PMID- 29443383
TI  - A B3GALT6 variant in patient originally described as Al-Gazali syndrome and
      implicating the endoplasmic reticulum quality control in the mechanism of some
      beta3GalT6-pathy mutations.
AB  - Al-Gazali syndrome encompasses several clinical features including prenatal
      growth retardation, large joints contractures with camptodactyly, bilateral
      talipes equinovarus, small mouth, anterior segment anomalies of the eyes, and
      early lethality. Recently, a baby with features very similar to Al-Gazali
      syndrome was found to have compound heterozygous variants in B3GALT6. This gene
      encodes Beta-1,3-galactosyltransferase 6 (beta3GalT6), an essential component of
      the glycosaminoglycan synthesis pathway. Pathogenic variants in B3GALT6 have also
      been shown to cause Ehlers-Danlos syndrome spondylodysplastic type (spEDS
      B3GALT6) and spondyloepimetaphyseal dysplasia with joint laxity type I (SEMD
      JL1). In 2017, a new international classification of EDS included these 2
      conditions together with the child reported to have features similar to Al-Gazali
      syndrome under spondylodysplastic EDS (spEDS). We report a disease-causing
      variant c.618C > G, p.(Cys206Trp) in 1 patient originally described as Al-Gazali
      syndrome and reported in 1999. We evaluated the involvement of the endoplasmic
      reticulum-associated protein degradation, in the pathogenesis of 13 B3GALT6
      variants. Retention in endoplasmic reticulum was evident in 6 of them while the
      c.618C > G, p.(Cys206Trp) and the other 6 variants trafficked normally. Our
      findings confirm the involvement of B3GALT6 in the pathogenesis of Al-Gazali
      syndrome and suggest that Al-Gazali syndrome represents the severe end of the
      spectrum of the phenotypes caused by pathogenic variants in this gene.

PMID- 29443384
TI  - Should statins be discontinued in cirrhosis with decompensation?

PMID- 29443385
TI  - Mercury and motor neuron disease: Hooked on a hypothesis.

PMID- 29443387
TI  - Predictors of early left ventricular systolic dysfunction in duchenne muscular
      dystrophy patients.
AB  - INTRODUCTION: Early detection of left ventricular systolic dysfunction (LVSD) is
      important for therapeutic strategies for Duchenne muscular dystrophy (DMD)
      patients. We analyzed myocardial strain using echocardiography for early
      detection of LVSD and determined the predictors of early LVSD. METHODS: This
      investigation was a cross-sectional study of 40 DMD patients with normal left
      ventricular ejection fraction. Global longitudinal strain (GLS) was used to
      analyze subtle disturbances in longitudinal contraction of the myocardium.
      Patients were determined to have early LVSD (GLS > -18) or normal left
      ventricular systolic function (GLS <= -18). RESULTS: Patients who had early LVSD
      were older and had a higher frequency of corticosteroid therapy and of mutations
      in exons 45, 46, 47, 48, 49, 50, and 52. DISCUSSION: Myocardial strain
      measurements are useful for the early diagnosis of LVSD in DMD patients. Older
      age, use of corticosteroids, and mutations within the "hot-spot" region of the
      DMD gene are associated with early LVSD. Muscle Nerve, 2018.

PMID- 29443386
TI  - Technical Note: Error metrics for estimating the accuracy of needle/instrument
      placement during transperineal magnetic resonance/ultrasound-guided prostate
      interventions.
AB  - PURPOSE: Image-guided systems that fuse magnetic resonance imaging (MRI) with
      three-dimensional (3D) ultrasound (US) images for performing targeted prostate
      needle biopsy and minimally invasive treatments for prostate cancer are of
      increasing clinical interest. To date, a wide range of different accuracy
      estimation procedures and error metrics have been reported, which makes comparing
      the performance of different systems difficult. METHODS: A set of nine measures
      are presented to assess the accuracy of MRI-US image registration, needle
      positioning, needle guidance, and overall system error, with the aim of providing
      a methodology for estimating the accuracy of instrument placement using a MR/US
      guided transperineal approach. RESULTS: Using the SmartTarget fusion system, an
      MRI-US image alignment error was determined to be 2.0 +/- 1.0 mm (mean +/- SD),
      and an overall system instrument targeting error of 3.0 +/- 1.2 mm. Three needle
      deployments for each target phantom lesion was found to result in a 100% lesion
      hit rate and a median predicted cancer core length of 5.2 mm. CONCLUSIONS: The
      application of a comprehensive, unbiased validation assessment for MR/US guided
      systems can provide useful information on system performance for quality
      assurance and system comparison. Furthermore, such an analysis can be helpful in
      identifying relationships between these errors, providing insight into the
      technical behavior of these systems.

PMID- 29443388
TI  - It is a long road to inclusive education for children with cerebral palsy.

PMID- 29443389
TI  - Can we trust the calculation of texture indices of CT images? A phantom study.
AB  - PURPOSE: Texture analysis is an emerging tool in the field of medical imaging
      analysis. However, many issues have been raised in terms of its use in assessing
      patient images and it is crucial to harmonize and standardize this new imaging
      measurement tool. This study was designed to evaluate the reliability of texture
      indices of CT images on a phantom including a reproducibility study, to assess
      the discriminatory capacity of indices potentially relevant in CT medical images
      and to determine their redundancy. METHODS: For the reproducibility and
      discriminatory analysis, eight identical CT acquisitions were performed on a
      phantom including one homogeneous insert and two close heterogeneous inserts.
      Texture indices were selected for their high reproducibility and capability of
      discriminating different textures. For the redundancy analysis, 39 acquisitions
      of the same phantom were performed using varying acquisition parameters and a
      correlation matrix was used to explore the 2 * 2 relationships. LIFEx software
      was used to explore 34 different parameters including first order and texture
      indices. RESULTS: Only eight indices of 34 exhibited high reproducibility and
      discriminated textures from each other. Skewness and kurtosis from histogram were
      independent from the six other indices but were intercorrelated, the other six
      indices correlated in diverse degrees (entropy, dissimilarity, and contrast of
      the co-occurrence matrix, contrast of the Neighborhood Gray Level difference
      matrix, SZE, ZLNU of the Gray-Level Size Zone Matrix). CONCLUSIONS: Care should
      be taken when using texture analysis as a tool to characterize CT images because
      changes in quantitation may be primarily due to internal variability rather than
      from real physio-pathological effects. Some textural indices appear to be
      sufficiently reliable and capable to discriminate close textures on CT images.

PMID- 29443390
TI  - Tolerance limits and methodologies for IMRT measurement-based verification QA:
      Recommendations of AAPM Task Group No. 218.
AB  - PURPOSE: Patient-specific IMRT QA measurements are important components of
      processes designed to identify discrepancies between calculated and delivered
      radiation doses. Discrepancy tolerance limits are neither well defined nor
      consistently applied across centers. The AAPM TG-218 report provides a
      comprehensive review aimed at improving the understanding and consistency of
      these processes as well as recommendations for methodologies and tolerance limits
      in patient-specific IMRT QA. METHODS: The performance of the dose
      difference/distance-to-agreement (DTA) and gamma dose distribution comparison
      metrics are investigated. Measurement methods are reviewed and followed by a
      discussion of the pros and cons of each. Methodologies for absolute dose
      verification are discussed and new IMRT QA verification tools are presented.
      Literature on the expected or achievable agreement between measurements and
      calculations for different types of planning and delivery systems are reviewed
      and analyzed. Tests of vendor implementations of the gamma verification algorithm
      employing benchmark cases are presented. RESULTS: Operational shortcomings that
      can reduce the gamma tool accuracy and subsequent effectiveness for IMRT QA are
      described. Practical considerations including spatial resolution, normalization,
      dose threshold, and data interpretation are discussed. Published data on IMRT QA
      and the clinical experience of the group members are used to develop guidelines
      and recommendations on tolerance and action limits for IMRT QA. Steps to check
      failed IMRT QA plans are outlined. CONCLUSION: Recommendations on delivery
      methods, data interpretation, dose normalization, the use of gamma analysis
      routines and choice of tolerance limits for IMRT QA are made with focus on
      detecting differences between calculated and measured doses via the use of robust
      analysis methods and an in-depth understanding of IMRT verification metrics. The
      recommendations are intended to improve the IMRT QA process and establish
      consistent, and comparable IMRT QA criteria among institutions.

PMID- 29443391
TI  - Human papillomavirus genome integration in squamous carcinogenesis: what have
      next-generation sequencing studies taught us?
AB  - Human papillomavirus (HPV) infection is associated with ~5% of all human cancers,
      including a range of squamous cell carcinomas. Persistent infection by high-risk
      HPVs (HRHPVs) is associated with the integration of virus genomes (which are
      usually stably maintained as extrachromosomal episomes) into host chromosomes.
      Although HRHPV integration rates differ across human sites of infection, this
      process appears to be an important event in HPV-associated neoplastic
      progression, leading to deregulation of virus oncogene expression, host gene
      expression modulation, and further genomic instability. However, the mechanisms
      by which HRHPV integration occur and by which the subsequent gene expression
      changes take place are incompletely understood. The advent of next-generation
      sequencing (NGS) of both RNA and DNA has allowed powerful interrogation of the
      association of HRHPVs with human disease, including precise determination of the
      sites of integration and the genomic rearrangements at integration loci. In turn,
      these data have indicated that integration occurs through two main mechanisms:
      looping integration and direct insertion. Improved understanding of integration
      sites is allowing further investigation of the factors that provide a competitive
      advantage to some integrants during disease progression. Furthermore, advanced
      approaches to the generation of genome-wide samples have given novel insights
      into the three-dimensional interactions within the nucleus, which could act as
      another layer of epigenetic control of both virus and host transcription. It is
      hoped that further advances in NGS techniques and analysis will not only allow
      the examination of further unanswered questions regarding HPV infection, but also
      direct new approaches to treating HPV-associated human disease. Copyright (c)
      2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 29443392
TI  - Spatial aspects of oncogenic signalling determine the response to combination
      therapy in slice explants from Kras-driven lung tumours.
AB  - A key question in precision medicine is how functional heterogeneity in solid
      tumours informs therapeutic sensitivity. We demonstrate that spatial
      characteristics of oncogenic signalling and therapy response can be modelled in
      precision-cut slices from Kras-driven non-small-cell lung cancer with varying
      histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that
      signalling stratifies mostly according to histopathology, showing enhanced AKT
      and SRC activity in adenosquamous carcinoma, and mitogen-activated protein kinase
      (MAPK) activity in adenocarcinoma. In addition, high intertumour and intratumour
      variability was detected, particularly of MAPK and mammalian target of rapamycin
      (mTOR) complex 1 activity. Using short-term treatment of slice explants, we
      showed that cytotoxic responses to combination MAPK and phosphoinositide 3-kinase
      mTOR inhibition correlate with the spatially defined activities of both pathways.
      Thus, whereas genetic drivers determine histopathology spectra, histopathology
      associated and spatially variable signalling activities determine drug
      sensitivity. Our study is in support of spatial aspects of signalling
      heterogeneity being considered in clinical diagnostic settings, particularly to
      guide the selection of drug combinations. (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- 29443393
TI  - Parenteral Nutrition Electrolyte Abnormalities and Associated Factors Before and
      After Nutrition Support Team Initiation.
AB  - BACKGROUND: Studied since the 1940s, refeeding syndrome still has no universal
      definition, thus making comparison of studies difficult. Negative outcomes (eg,
      metabolic abnormalities) may occur with the use of specialized nutrition, such as
      parenteral nutrition (PN). Less than half of medical institutions have a
      nutrition support team (NST) managing PN. Interdisciplinary team management of PN
      may reduce negative outcomes of PN. The objective of this study was to show the
      value of the NST by measuring differences in PN variables, especially electrolyte
      abnormalities (EAs), before and after NST initiation at a large medical center
      and to identify factors associated with EAs among adult subjects receiving PN.
      MATERIALS AND METHODS: During this retrospective study, computerized medical
      charts (N = 735) from 2007-2010 were reviewed for electrolyte changes
      (particularly potassium, magnesium, and phosphorus) the first 3 days following PN
      initiation in hospitalized adults. Changes in EAs with other variables were
      compared before and after NST implementation. Equivalent samples sizes were
      collected to better evaluate the impact of the team. RESULTS: Following the
      implementation of the NST, fewer EAs were seen in PN patients (53%; chi2  =
      10.906, P = .004); significantly less potassium, phosphorus, and magnesium
      intravenous piggyback supplementation (88.8% vs 94%; chi2  = 5.05, P = .026) was
      used; and mortality within 30 days of PN cessation was significantly less (12.7%
      vs 10.6%, P = .012). CONCLUSION: Our study complements existing research, finding
      that an NST was associated with a decreased occurrence of EAs and mortality in
      the hospitalized adult receiving PN.

PMID- 29443394
TI  - Catheter-Related Bloodstream Infections in Adults Receiving Home Parenteral
      Nutrition: Substantial Differences in Incidence Comparing a Strict
      Microbiological to a Clinically Based Diagnosis.
AB  - BACKGROUND: A common complication in patients receiving home parenteral nutrition
      (HPN) is catheter-related bloodstream infections (CRBSIs). The CRBSI incidence
      has been advocated as an outcome parameter assessing the quality of care. This
      study aimed to illustrate how the use of different CRBSI definitions affects the
      reported incidence. MATERIALS AND METHODS: In an observational study based on the
      Copenhagen intestinal failure database, all clinically reported CRBSIs from 2002
      2013 were compared with data from the affiliated microbiological database
      according to recommended CRBSI criteria. RESULTS: Clinically, 1034 CRBSIs were
      observed in 548 adults receiving HPN for 1410 catheter-years. Thus, the
      clinically assessed CRBSI incidence was 1.95/1000 catheter-days. However, based
      on the microbiological evaluation, only 47% of our episodes fulfilled the Centers
      for Disease Control and Prevention (CDC) and European Society for Clinical
      Nutrition (ESPEN) CRBSI criteria. Employing a catheter-salvaging strategy, 40% of
      the CRBSI diagnoses were supported by the paired blood culture positivity
      criteria and only 6% by a positive catheter tip. In 53%, CRBSIs were categorized
      as a clinical or "probable CRBSI" diagnosis. In 20% of all episodes, missing
      information/blood cultures hampered a CDC/ESPEN CRBSI diagnosis. Thereby,
      according to CDC/ESPEN CRBSI definitions, the incidence was 0.92/1000 days or 46%
      lower than clinically assessed. CONCLUSION: This study illustrates the practical
      and methodological challenges and great variability in reporting of the CRBSI
      incidence. Nonetheless, it is recommended as a marker of the quality of care.
      Consensus regarding CRBSI definitions is a prerequisite for a meaningful
      comparison of this important outcome parameter between HPN centers.

PMID- 29443395
TI  - Subcutaneous Infusion of Fluids for Hydration or Nutrition: A Review.
AB  - Subcutaneous infusion, or hypodermoclysis, is a technique whereby fluids are
      infused into the subcutaneous space via small-gauge needles that are typically
      inserted into the thighs, abdomen, back, or arms. In this review, we provide an
      overview of the technique, summarize findings from studies that have examined the
      use of subcutaneous infusion of fluids for hydration or nutrition, and describe
      the indications, advantages, and disadvantages of subcutaneous infusion. Taken
      together, the available evidence suggests that, when indicated, subcutaneous
      infusion can be effective for administering fluids for hydration or nutrition,
      with minimal complications, and has similar effectiveness and safety to the
      intravenous route. Of note, subcutaneous infusion offers several advantages over
      intravenous infusion, including ease of application, low cost, and the lack of
      potential serious complications, particularly infections. Subcutaneous infusion
      may be particularly suited for patients with mild to moderate dehydration or
      malnutrition when oral/enteral intake is insufficient; when placement of an
      intravenous catheter is not possible, tolerated, or desirable; at risk of
      dehydration when oral intake is not tolerated; as a bridging technique in case of
      difficult intravenous access or catheter-related bloodstream infection while
      infection control treatment is being attempted; and in multiple settings (eg,
      emergency department, hospital, outpatient clinic, nursing home, long-term care,
      hospice, and home).

PMID- 29443396
TI  - Infants on Parenteral Nutrition: Getting the Calories Right.

PMID- 29443397
TI  - Whole Body Protein Turnover and Net Protein Balance After Pediatric Thoracic
      Surgery: A Noninvasive Single-Dose 15 N Glycine Stable Isotope Protocol With End
      Product Enrichment.
AB  - BACKGROUND: We used the 15 N glycine urinary end-product enrichment technique to
      quantify whole body protein turnover following thoracic surgery. MATERIALS AND
      METHODS: A single dose of 15 N glycine (2 mg/kg) was administered orally on
      postoperative day 1 to children (1-18 years) following thoracic surgery. 15 N
      enrichment of ammonia and urea was measured in mixed urine after 12 and 24 hours,
      respectively, and protein synthesis, breakdown, and net balance determined.
      Nitrogen balance (dietary intake minus urinary excretion) was calculated. Urinary
      3-methylhistidine:creatinine ratio was measured as a marker of skeletal muscle
      protein breakdown. RESULTS: We enrolled 19 subjects-median (interquartile range):
      age, 13.8 years (12.2-15.1); weight, 49.2 kg (38.4-60.8)-who underwent
      thoracotomy (n = 12) or thoracoscopic (n = 7) surgery. Protein synthesis and
      breakdown by 15 N enrichment were 7.1 (5.5-9) and 7.1 (5.6-9) g.kg-1 .d-1 with
      ammonia (12 hours) as the end product, and 5.8 (3.8-6.7) and 6.7 (4.5-7.6) with
      urea (24 hours), respectively. Net protein balance by the 15 N glycine and
      urinary urea nitrogen methods were -0.34 (-0.47, -0.3) and -0.48 (-0.65, -0.28)
      g.kg-1 .d-1 , respectively (rs = 0.828, P < .001). Postoperative change in 3
      methylhistidine:creatinine ratio did not correlate significantly with protein
      breakdown or balance. CONCLUSION: The single-dose oral administration of 15 N
      glycine stable isotope with measurement of urinary end-product enrichment is a
      feasible and noninvasive method to investigate whole body protein turnover in
      children. After major surgery, children manifest increased protein turnover and
      net negative balance due to increased protein breakdown.

PMID- 29443398
TI  - JPEN Journal Club 32. Adjusting for Confounding.

PMID- 29443399
TI  - Two-Year Neurodevelopment and Growth Outcomes for Preterm Neonates Who Received
      Low-Dose Intravenous Soybean Oil.
AB  - BACKGROUND: In some studies, the dose of intravenous soybean oil (SO) has been
      associated with a decreased incidence of intestinal failure-associated liver
      disease. The effect of lipid sparing on neurodevelopment (ND) and growth remains
      unknown. This study investigated the impact of SO dose on ND and growth over the
      first 2 years of age in preterm neonates. MATERIALS AND METHODS: This is a single
      site prospective follow-up study. Neonates with a gestational age <=29 weeks were
      randomized to low-dose (LOW) or standard-dose (CON) SO. Bayley Scales of Infant
      Development III and anthropometric measurements were collected at approximately
      6, 12, and 24 months corrected gestational age. RESULTS: Subjects were premature,
      with a mean (+/-SD) gestational age of 28 +/- 1 and 27 +/- 1 weeks (P = .3) for
      LOW and CON, respectively. Thirty subjects completed follow-up (LOW = 15, CON =
      15). There were no differences for ND and growth outcomes when LOW was compared
      with CON, with the exception of a higher 12-month follow-up cognitive scaled
      score in the LOW group (P = .02). CONCLUSION: A reduced SO dose did not adversely
      affect ND or growth in this cohort of preterm neonates. However, larger studies
      are needed to determine the long-term safety of SO dose reduction before this
      strategy can be adopted.

PMID- 29443400
TI  - Barriers to Nutrition Intervention for Patients With a Traumatic Brain Injury:
      Views and Attitudes of Medical and Nursing Practitioners in the Acute Care
      Setting.
AB  - BACKGROUND: Nutrition delivered to patients with a traumatic brain injury (TBI)
      is typically below prescribed amounts. While the dietitian plays an important
      role in the assessment and provision of nutrition needs, they are part of a
      multidisciplinary team. The views and attitudes of medical and nursing
      practitioners are likely to be crucial to implementation of nutrition to patients
      with TBI, but there is limited information describing these. METHODS: A
      qualitative exploratory approach was used to explore the views and attitudes of
      medical and nursing practitioners on nutrition for patients with TBI.
      Participants at 2 major neurotrauma hospitals in Australia completed individual
      semi-structured interviews with a set of questions and a case study. Interviews
      were transcribed and coded for themes. RESULTS: Thirty-four health practitioners
      participated: 18 nurses and 16 physicians. Three major themes emerged: (1)
      nutrition practices over the hospital admission reflect the recovery course, (2)
      there are competing priorities when caring for patients with TBI, and (3) the
      implementation of nutrition therapy is influenced by practitioner roles and
      expectations. CONCLUSION: Use of qualitative inquiry in the study of attitudes
      toward nutrition provision to patients with TBI provided detailed insights into
      the challenges of operationalizing nutrition therapy. These insights can be used
      to clarify communication between health practitioners working with patients with
      TBI across the continuum of care.

PMID- 29443401
TI  - Pediatric Intestinal Failure-Associated Liver Disease: Challenges in Identifying
      Clinically Relevant Biomarkers.
AB  - BACKGROUND: Intestinal failure-associated liver disease (IFALD) is complex and
      diagnosed by concurrent use of parenteral nutrition, clinical presentation, and
      alterations in hepatic biomarkers exclusive of other causes of liver disease. In
      comparison with individual measures, composite biomarkers may provide a more
      effective means for assessing disease progression and response to treatment than
      single parameters. Since IFALD is considered by some to be a type of drug-induced
      liver injury (DILI), those diagnostic criteria could potentially be used in this
      population. Using a preexisting database of children treated for IFALD, our aim
      was to determine if a similar composite biomarker could be applied to this
      population. STUDY DESIGN: Adult DILI criteria were applied at baseline, when
      treatment for IFALD (ie, direct bilirubin >=2.0 mg/dL) was initiated. RESULTS: A
      total of 214 patients with IFALD treated at Boston Children's Hospital were
      identified; 168 patients were eligible for analysis. Most patients analyzed were
      male (61%) and preterm (87%). Alkaline phosphatase (ALP) >=2* upper limit of
      normal (ULN) captured the least amount of DILI (11%), while gamma
      glutamyltransferase (GGT) >=1* ULN accounted for the most (62%). Using adult DILI
      criteria, 60 (39%) patients with IFALD were found to have DILI. Substituting GGT
      >=1* ULN for ALP >=2* ULN improved the sensitivity, with 105 (69%) of patients
      meeting at least 1 criterion for DILI. CONCLUSION: Numerous challenges made it
      difficult to apply the DILI criteria to children with IFALD. Direct bilirubin,
      fractionated ALP, and perhaps GGT may be more suitable. Given its complex
      etiology and the age-based differences due to hepatic immaturity and growth, a
      more suitable composite marker needs to be developed to assess IFALD in this
      population.

PMID- 29443402
TI  - ASPEN NUTRITION SCIENCE AND PRACTICE CONFERENCE: Las Vegas, Nevada, January 22
      25, 2018: Vars Candidates, Trainee Awards, Best of ASPEN (Topic Awards),
      International Awards, Abstracts of Distinction, Posters of Distinction and Other
      Abstracts.

PMID- 29443404
TI  - New, Immunomodulatory, Oral Nutrition Formula for Use Prior to Surgery in
      Patients With Head and Neck Cancer: An Exploratory Study.
AB  - BACKGROUND: The perioperative use of immunomodulatory nutrition formulas in
      patients with head and neck cancer reduces the number of postoperative infections
      and the length of hospital stay. OBJECTIVE: An exploratory, randomized,
      controlled, blind, clinical trial was designed to examine the effect of the
      preoperative consumption of a new, immunomodulatory, oral nutrition formula in
      patients with head and neck cancer. METHODS: Thirty-eight patients were
      randomized to receive either 400 mL/d of either the new immunomodulatory formula
      (IF) or that commonly used in clinical practice (CF) over 10 days prior to
      surgery. Thirty-three patients completed the study. Compliance, tolerance, the
      length of hospital stay, the incidence of infections and noninfectious
      complications before discharge, and the same up to 15 and 30 days after discharge
      were recorded. RESULTS: The percentage of patients who developed infections
      before discharge was significantly lower in the IF than in the CF group (P =
      .013), as was the number of infections/100 patients/d (P = .035). The length of
      hospital stay was significantly shorter in the IF group (P = .001). Both formulas
      were safe and well tolerated. No other differences were detected. These results
      suggest preoperative consumption of the new formula to be beneficial for patients
      with neck and head cancer. Further trials are needed to confirm these results and
      to test the efficacy of the formula in patients with other conditions.
      CONCLUSION: The new formula can be safely prescribed as part of the preoperative
      treatment of patients with head and neck cancer and might reduce the problem of
      postoperative infection.

PMID- 29443405
TI  - Vascular access considerations for extracorporeal photopheresis.
AB  - Extracorporeal photopheresis is an immunomodulatory therapy indicated for
      patients with cutaneous T-cell lymphoma, graft-versus-host disease, and heart or
      lung allograft rejection. Whole blood from the patient is drawn into the
      photopheresis instrument where it is separated into its components. Plasma, red
      blood cells, and the treated buffy coat are subsequently returned to the patient.
      Consistent, adequate blood flow is necessary to successfully complete the
      procedure. Vascular access options for photopheresis include peripheral vein
      cannulation, tunneled central venous catheters, and subcutaneous ports.
      Photopheresis is a very safe procedure; however, the complications and impact on
      the patient's quality of life associated with vascular access devices can be
      significant.

PMID- 29443406
TI  - Implantable vascular access devices - past, present, and future.

PMID- 29443407
TI  - Implanted vascular access device options: a focused review on safety and
      outcomes.
AB  - Implantable vascular access devices are frequently used in patients who have poor
      peripheral venous access. These devices can be partially implanted as tunneled
      and nontunneled central catheters, or they can be fully implanted as ports.
      Compared with long-term catheters, implanted ports have lower infection rates and
      improved perceptions of quality of life, but complications still occur in 2% to
      18% of patients, frequently requiring removal of the device. Since the conception
      of implantable vascular access device ports, numerous advances in port design,
      materials, and techniques for implantation and care have been developed with the
      goal of overcoming frequent complications. We review the evidence related to
      these advances and their effect on the safety profile and complications of
      implantable vascular access device ports.

PMID- 29443408
TI  - Vascular access for red blood cell exchange.
AB  - Red blood cell exchange is the process of removing red blood cells from a patient
      and replacing them with donated blood using either automated or manual
      techniques. Red blood cell exchange is a well-recognized and effective therapy
      for many red blood cell-related diseases, especially sickle cell disease.
      However, decisions regarding the best methods for vascular access are not
      intuitive and must account for the patient's clinical condition, complication
      risks, and lifestyle, especially in the context of long-term vascular access. In
      this review, we discuss the recognized indications for red blood cell exchange,
      considerations for the selection of exchange modality and vascular access, and
      recommendations for the appropriate care and prevention of risks associated with
      vascular access.

PMID- 29443403
TI  - Proceedings of the 2017 ASPEN Research Workshop-Gastric Bypass: Role of the Gut.
AB  - The goal of the National Institutes of Health-funded American Society for
      Parenteral and Enteral Nutrition 2017 research workshop (RW) "Gastric Bypass:
      Role of the Gut" was to focus on the exciting research evaluating gut-derived
      signals in modulating outcomes after bariatric surgery. Although gastric bypass
      surgery has undoubted positive effects, the mechanistic basis of improved
      outcomes cannot be solely explained by caloric restriction. Emerging data suggest
      that bile acid metabolic pathways, luminal contents, energy balance, gut mucosal
      integrity, as well as the gut microbiota are significantly modulated after
      bariatric surgery and may be responsible for the variable outcomes, each of which
      was rigorously evaluated. The RW served as a timely and novel academic meeting
      that brought together clinicians and researchers across the scientific spectrum,
      fostering a unique venue for interdisciplinary collaboration among investigators.
      It promoted engaging discussion and evolution of new research hypotheses and
      ideas, driving the development of novel ameliorative, therapeutic, and
      nonsurgical interventions targeting obesity and its comorbidities. Importantly, a
      critical evaluation of the current knowledge regarding gut-modulated signaling
      after bariatric surgery, potential pitfalls, and lacunae were thoroughly
      addressed.

PMID- 29443409
TI  - Cellular collection by apheresis.
AB  - Cellular collection is an important and increasingly used apheresis procedure.
      These collections are performed by leukocytapheresis, a procedure involving the
      removal of a patient's or donor's white blood cells, and are used to collect
      hematopoietic progenitor cells, specific cell populations (such as T
      lymphocytes), and granulocytes. Hematopoietic progenitor cell apheresis and T
      lymphocyte collection are performed by procedures that enrich for mononuclear
      cells. Hematopoietic progenitor cells are used for autologous and allogeneic
      hematopoietic stem cell transplantation, whereas T-cell collection is being used
      increasingly in novel cellular therapy approaches and for donor lymphocyte
      infusions to induce graft-versus-leukemia effect. Granulocytes are collected from
      healthy donors to treat severe sepsis in patients who are refractory to
      antimicrobial therapies. Less frequently, cellular depletion of leukocytes may be
      indicated in leukemic patients who have severe hyperleukocytosis resulting in
      leukoaggregation and decreased tissue perfusion. In these procedures,
      establishing and maintaining adequate vascular access are critical prerequisites
      to ensuring a successful procedure. For most types of leukocytapheresis
      procedures, efforts should be made to ensure that they are performed using
      peripheral veins, and the use of an intravascular access device should be
      considered only after it is determined that peripheral access is not feasible or
      desirable. However, in some settings (such as in patients undergoing autologous
      hematopoietic stem cell transplantation), intravascular access devices are often
      used to facilitate both the leukocytapheresis procedure and the subsequent
      transplant. Here, different types of vascular access approaches used in cellular
      collections are discussed, and this information is supplemented by the author's
      experience and practice in areas where published information is limited.

PMID- 29443410
TI  - A tale of two ports: an in vitro comparison of flow characteristics for
      therapeutic plasma exchange.
AB  - Tunneled central venous catheters with ports are increasingly used for
      therapeutic apheresis procedures. Vortex ports have been used as access for
      therapeutic apheresis procedures, but are not ideal for therapeutic plasma
      exchange (TPE) procedures due to lower flow rates. We performed an in vitro
      experiment to compare flow characteristics of the single-lumen Vortex port
      (AngioDynamics) with the single-lumen TidalPort (Norfolk Medical). We used
      expired red blood cell units and adjusted the hematocrit to 40% with normal
      saline in a 2-L bag. We programmed the Spectra Optia (Terumo BCT) to run a 1.0
      volume TPE with 5% albumin as replacement fluid. The TidalPort achieved flow
      rates of up to 110 mL/min without triggering alarms. Due to crucial alarms, the
      Vortex Port was not able to run at a flow rate higher than 90 mL/min, and
      multiple caution alarms were triggered at flow rates of 80 to 90 mL/min. These
      findings suggest that the TidalPort may be a suitable access option that provides
      flow rates similar to peripheral or central venous catheters for TPE procedures.

PMID- 29443411
TI  - Intravascular access devices from an interventional radiology perspective:
      indications, implantation techniques, and optimizing patency.
AB  - Central venous access has become invaluable in the treatment of patients with a
      wide array of acute and chronic disease entities. Central venous catheters
      provide durable, short-term and long-term access solutions while saving the
      patient from repeated peripheral needle sticks. Central venous catheters include:
      non-tunneled central venous catheters, tunneled central venous catheters, and
      port catheters. Typically, the placement of a central venous catheter is
      performed by Vascular and Interventional Radiologists. The purpose of this
      article is to familiarize the reader with the role of Interventional Radiology in
      the placement and management of intravascular or implantable access devices, with
      a focus on discussing indications for central venous catheter placement,
      implantation techniques, potential complications, and management of catheter
      dysfunction.

PMID- 29443412
TI  - An ex vivo comparison of vascular access devices used in extracorporeal
      photopheresis.
AB  - BACKGROUND: Central venous access devices are commonly used in extracorporeal
      photopheresis, but their performance has not been systematically evaluated. The
      primary objective of this study was to compare pressures at various flow rates
      for central venous access devices in an ex vivo simulation of photopheresis.
      STUDY DESIGN AND METHODS: Diluted, heparinized red blood cells were circulated
      through central access devices in series with a photopheresis system, and
      pressures at several flow rates were recorded. The devices tested were the
      Trifusion catheter (Hickman), the Vortex single-lumen and dual-lumen ports
      (Angiodynamics), and the TidalPort device (Norfolk). Flow rates were also
      compared for silicone and polyurethane catheters and for different catheter
      internal diameters. RESULTS: The Vortex dual-lumen port generated pressure alarms
      above flow rates of 60 mL/minute. Throughout flow rates from 5 to 100 mL/minute,
      the Trifusion catheter and the TidalPort device operated at lower pressures than
      the Vortex ports. Within typical clinical flow rates, neither catheter material
      nor internal diameter substantially affected pressure. CONCLUSION: Central venous
      access devices show large differences in pressure within flow rates used
      routinely in clinical settings. These differences cannot be fully attributed to
      catheter material composition or catheter internal diameter.

PMID- 29443413
TI  - Vascular access for therapeutic plasma exchange.
AB  - Therapeutic plasma exchange is an apheresis modality in which plasma is separated
      from the blood cellular components ex vivo, discarded, and replaced with an
      isosmotic fluid (most commonly 5% albumin) to maintain appropriate oncotic
      pressure in the patient. Therapeutic plasma exchange is used in the treatment of
      many diseases and indications. The recent seventh edition of the American Society
      for Apheresis guidelines indicates approximately 72 diseases and 116 indications
      for which therapeutic plasma exchange may be effective. One of the critical
      aspects for the successful performance of therapeutic plasma exchange is
      appropriate vascular access to provide high blood flow for the collection and
      return phases of the procedure, especially because most patients who need
      therapeutic plasma exchange will require more than one treatment over days to
      weeks. This article provides an overview of the characteristics of therapeutic
      plasma exchange, the clinical diseases and indications that may be treated with
      therapeutic plasma exchange, and the different types of vascular access employed,
      with their advantages and disadvantages. The latter may include peripheral venous
      access and intravascular or implantable access devices, such as arteriovenous
      grafts and fistulas, central venous catheters, and central venous catheters
      tunneled with ports.

PMID- 29443414
TI  - Neonatal outcomes after fetal exposure to methadone and buprenorphine: national
      registry studies from the Czech Republic and Norway.
AB  - BACKGROUND AND AIMS: Opioid maintenance treatment (OMT) is recommended to opioid
      dependent females during pregnancy. However, it is not clear which medication
      should be preferred. We aimed to compare neonatal outcomes after prenatal
      exposure to methadone (M) and buprenorphine (B) in two European countries.
      DESIGN: Nation-wide register-based cohort study using personalized IDs assigned
      to all citizens for data linkage. SETTING: The Czech Republic (2000-14) and
      Norway (2004-13). [Correction added after online publication on 26 April 2018:
      The Czech Republic (2000-04) corrected to (2000-14).] PARTICIPANTS: Opioid
      dependent pregnant Czech (n = 333) and Norwegian (n = 235) women in OMT who
      received either B or M during pregnancy and their newborns. MEASUREMENTS: We
      linked data from health registries to identify the neonatal outcomes: gestational
      age, preterm birth, birth weight, length and head circumference, small for
      gestational age, miscarriages and stillbirth, neonatal abstinence syndrome (NAS)
      and Apgar score. We performed multivariate linear regression and binary logistic
      regression to explore the associations between M and B exposure and outcomes.
      Regression coefficient (beta) and odds ratio (OR) were computed. FINDINGS: Most
      neonatal outcomes were more favourable after exposure to B compared with M, but
      none of the differences was statistically significant. For instance, in the
      multivariate analysis, birth weight was beta = 111.6 g [95% confidence interval
      (CI) = -10.5 to 233.6 and beta = 83.1 g, 95% CI = -100.8 to 267.0] higher after B
      exposure in the Czech Republic and Norway, respectively. Adjusted OR of NAS for B
      compared with M was 0.94 (95% CI = 0.46-1.92) in the Norwegian cohort.
      CONCLUSIONS: Two national cohorts of women receiving opioid maintenance treatment
      during pregnancy showed small but not statistically significant differences in
      neonatal outcomes in favour of buprenorphine compared with methadone.

PMID- 29443415
TI  - Comprehensive assessment of the donor-site of the anterolateral thigh flap: A
      prospective study in 33 patients.
AB  - BACKGROUND: The anterolateral thigh (ALT) free flap has been an extremely
      versatile flap. The purpose of this study was to propose comprehensive functional
      assessments of the donor site. METHODS: A total of 33 ALT flaps were enrolled
      prospectively. Objective assessments included isokinetic testing of the knee, and
      electromyographic examination of the lateral femoral cutaneous nerve (LFCN). The
      Patient and Observer Scar Assessment Scale (POSAS) was used to subjectively
      assess the donor-site scar. RESULTS: On the donor side, a significant decrease in
      most isokinetic muscle strength values was obvious 1 year postoperatively (P <
      .01). The normal side showed a compensatory increase 1 year postoperatively in
      the majority of isokinetic muscle strength values (P < .05). The majority of
      patients (70%) showed decreased sensory conduction velocity of the LFCN or no
      response to the microcurrent stimulation postoperatively. The aesthetic outcome
      was satisfactory. CONCLUSION: The decline in functional parameters at the donor
      site was common. However, much more research is needed.

PMID- 29443416
TI  - Diabetic neuropathy differs between type 1 and type 2 diabetes: Insights from
      magnetic resonance neurography.
AB  - OBJECTIVE: To visualize and quantify differences of microstructural nerve damage
      in distal symmetric diabetic neuropathy (DPN) between type 1 diabetes (T1D) and
      type 2 diabetes (T2D), and to detect correlations between neuropathic symptoms
      and serological risk factors. METHODS: Three-tesla magnetic resonance neurography
      of the sciatic nerve was performed in 120 patients (T1D, n = 35; T2D, n = 85)
      with either DPN (n = 84) or no DPN (n = 36). Results were subsequently correlated
      with clinical, serological, and electrophysiological patient data. RESULTS: T2
      weighted (T2w)-hyperintense lesions correlated negatively with tibial compound
      motor action potential (r = -0.58, p < 0.0001) and peroneal nerve conduction (r =
      0.51, p = 0.0002), and positively with neuropathy disability score (NDS; r = 
      0.54, p < 0.0001), neuropathy symptom score (NSS; r = 0.52, p < 0.0001), and
      HbA1c level (r = 0.23, p = 0.014). T2w-hypointense lesions correlated positively
      with NDS (r = 0.28, p = 0.002), NSS (r = 0.36, p < 0.0001), and serum
      triglycerides (r = 0.34, p = 0.0003), and negatively with serum high-density
      lipoprotein (HDL; r = -0.48, p < 0.0001). For DPN in T1D, elevated values of T2w
      hyperintense lesions (19.67 +/- 4.13% vs 12.49 +/- 1.23%, p = 0.027) and HbA1c
      (8.74 +/- 0.29% vs 7.11 +/- 0.16%, p < 0.0001) were found when compared to T2D.
      For DPN in T2D, elevated T2w-hypointense lesions (23.41 +/- 2.69mm3 vs 11.43 +/-
      1.74mm3 , p = 0.046) and triglycerides (220.70 +/- 23.70mg/dl vs 106.60 +/-
      14.51mg/dl, p < 0.0001), and lower serum HDL (51.29 +/- 3.02mg/dl vs 70.79 +/-
      4.65mg/dl, p < 0.0001) were found when compared to T1D. INTERPRETATION: The
      predominant type of nerve lesion in DPN differs between T1D and T2D. Correlations
      found between lesion type and serological parameters indicate that predominant
      nerve lesions in T1D are associated with poor glycemic control and loss of nerve
      conduction, whereas predominant lesions in T2D are associated with changes in
      lipid metabolism. These findings may be helpful for future studies on the
      underlying pathophysiological pathways and possible treatments for DPN in T1D and
      T2D. Ann Neurol 2018;83:588-598.

PMID- 29443417
TI  - Chemokines and receptors in intestinal B lymphocytes.
AB  - Recent studies indicate that chemoattractant cytokines (chemokines) and their
      receptors modulate intestinal B lymphocytes in different ways, including
      regulating their maturity and differentiation in the bone marrow and homing to
      intestinal target tissues. Here, we review several important chemokine/chemokine
      receptor axes that guide intestinal B cells, focusing on the homing and migration
      of IgA antibody-secreting cells (IgA-ASCs) to intestinal-associated lymphoid
      tissues. We describe the selective regulation of these chemokine axes in
      coordinating the IgA-ASC trafficking in intestinal diseases. Finally, we discuss
      the role of B cells as chemokine producers serving dual roles in regulating the
      mucosal immune microenvironment.

PMID- 29443418
TI  - Potential roles of YCF54 and ferredoxin-NADPH reductase for magnesium
      protoporphyrin monomethylester cyclase.
AB  - Chlorophyll is synthesized from activated glutamate in the tetrapyrrole
      biosynthesis pathway through at least 20 different enzymatic reactions. Among
      these, the MgProto monomethylester (MgProtoME) cyclase catalyzes the formation of
      a fifth isocyclic ring to tetrapyrroles to form protochlorophyllide. The enzyme
      consists of two proteins. The CHL27 protein is proposed to be the catalytic
      component, while LCAA/YCF54 likely acts as a scaffolding factor. In comparison to
      other reactions of chlorophyll biosynthesis, this enzymatic step lacks clear
      elucidation and it is hardly understood, how electrons are delivered for the
      NADPH-dependent cyclization reaction. The present study intends to elucidate more
      precisely the role of LCAA/YCF54. Transgenic Arabidopsis lines with inactivated
      and overexpressed YCF54 reveal the mutual stability of YCF54 and CHL27. Among the
      YCF54-interacting proteins, the plastidal ferredoxin-NADPH reductase (FNR) was
      identified. We showed in N. tabacum and A. thaliana that a deficit of FNR1 or
      YCF54 caused MgProtoME accumulation, the substrate of the cyclase, and
      destabilization of the cyclase subunits. It is proposed that FNR serves as a
      potential donor for electrons required in the cyclase reaction and connects
      chlorophyll synthesis with photosynthetic activity.

PMID- 29443419
TI  - Sex chromosomes and speciation in birds and other ZW systems.
AB  - Theory and empirical patterns suggest a disproportionate role for sex chromosomes
      in evolution and speciation. Focusing on ZW sex determination (females ZW, males
      ZZ; the system in birds, many snakes, and lepidopterans), I review how
      evolutionary dynamics are expected to differ between the Z, W and the autosomes,
      discuss how these differences may lead to a greater role of the sex chromosomes
      in speciation and use data from birds to compare relative evolutionary rates of
      sex chromosomes and autosomes. Neutral mutations, partially or completely
      recessive beneficial mutations, and deleterious mutations under many conditions
      are expected to accumulate faster on the Z than on autosomes. Sexually
      antagonistic polymorphisms are expected to arise on the Z, raising the
      possibility of the spread of preference alleles. The faster accumulation of many
      types of mutations and the potential for complex evolutionary dynamics of
      sexually antagonistic traits and preferences contribute to a role for the Z
      chromosome in speciation. A quantitative comparison among a wide variety of bird
      species shows that the Z tends to have less within-population diversity and
      greater between-species differentiation than the autosomes, likely due to both
      adaptive evolution and a greater rate of fixation of deleterious alleles. The W
      chromosome also shows strong potential to be involved in speciation, in part
      because of its co-inheritance with the mitochondrial genome. While theory and
      empirical evidence suggest a disproportionate role for sex chromosomes in
      speciation, the importance of sex chromosomes is moderated by their small size
      compared to the whole genome.

PMID- 29443420
TI  - Experimentally altered rainfall regimes and host root traits affect grassland
      arbuscular mycorrhizal fungal communities.
AB  - Future climate scenarios predict changes in rainfall regimes. These changes are
      expected to affect plants via effects on the expression of root traits associated
      with water and nutrient uptake. Associated microorganisms may also respond to
      these new precipitation regimes, either directly in response to changes in the
      soil environment or indirectly in response to altered root trait expression. We
      characterized arbuscular mycorrhizal (AM) fungal communities in an Australian
      grassland exposed to experimentally altered rainfall regimes. We used Illumina
      sequencing to assess the responses of AM fungal communities associated with four
      plant species sampled in different watering treatments and evaluated the extent
      to which shifts were associated with changes in root traits. We observed that
      altered rainfall regimes affected the composition but not the richness of the AM
      fungal communities, and we found distinctive communities in the increased
      rainfall treatment. We found no evidence of altered rainfall regime effects via
      changes in host physiology because none of the studied traits were affected by
      changes in rainfall. However, specific root length was observed to correlate with
      AM fungal richness, while concentrations of phosphorus and calcium in root tissue
      and the proportion of root length allocated to fine roots were correlated to
      community composition. Our study provides evidence that climate change and its
      effects on rainfall may influence AM fungal community assembly, as do plant
      traits related to plant nutrition and water uptake. We did not find evidence that
      host responses to altered rainfall drive AM fungal community assembly in this
      grassland ecosystem.

PMID- 29443421
TI  - Diabetes UK evidence-based nutrition guidelines for the prevention and management
      of diabetes.
AB  - A summary of the latest evidence-based nutrition guidelines for the prevention
      and management of diabetes is presented. These guidelines are based on existing
      recommendations last published in 2011, and were formulated by an expert panel of
      specialist dietitians after a literature review of recent evidence.
      Recommendations have been made in terms of foods rather than nutrients wherever
      possible. Guidelines for education and care delivery, prevention of Type 2
      diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular
      disease risk management, management of diabetes-related complications, other
      considerations including comorbidities, nutrition support, pregnancy and
      lactation, eating disorders, micronutrients, food supplements, functional foods,
      commercial diabetic foods and nutritive and non-nutritive sweeteners are
      included. The sections on pregnancy and prevention of Type 2 diabetes have been
      enlarged and the weight management section modified to include considerations of
      remission of Type 2 diabetes. A section evaluating detailed considerations in
      ethnic minorities has been included as a new topic. The guidelines were graded
      using adapted 'GRADE' methodology and, where strong evidence was lacking, grading
      was not allocated. These 2018 guidelines emphasize a flexible, individualized
      approach to diabetes management and weight loss and highlight the emerging
      evidence for remission of Type 2 diabetes. The full guideline document is
      available at www.diabetes.org.uk/nutrition-guidelines.

PMID- 29443422
TI  - Linking dendroecology and association genetics in natural populations: Stress
      responses archived in tree rings associate with SNP genotypes in silver fir
      (Abies alba Mill.).
AB  - Genetic association studies in forest trees would greatly benefit from
      information on the response of trees to environmental stressors over time, which
      can be provided by dendroecological analysis. Here, we jointly analysed
      dendroecological and genetic data of surviving silver fir trees to explore the
      genetic basis of their response to the iconic stress episode of the 1970s and
      1980s that led to large-scale forest dieback in Central Europe and has been
      attributed to air pollution. Specifically, we derived dendrophenotypic measures
      from 190 trees in the Bavarian Forest that characterize the resistance,
      resilience and recovery during this growth depression, and in the drought year in
      1976. By focusing on relative growth changes of trees and by standardizing the
      dendrophenotypes within stands, we accounted for variation introduced by micro-
      and macroscale environmental differences. We associated the dendrophenotypes with
      single nucleotide polymorphisms (SNPs) in candidate genes using general linear
      models (GLMs) and the machine learning algorithm random forest with subsequent
      feature selection. Most trees at our study sites experienced a severe growth
      decline from 1974 until the mid-1980s with minimum values during the drought
      year. Fifteen genes were associated with the dendrophenotypes, including genes
      linked to photosynthesis and drought stress. With our study, we show that
      dendrophenotypes can be a powerful resource for genetic association studies that
      permit to account for micro- and macroenvironmental variation when data are
      derived from natural populations. We call for a wider collaboration of
      dendroecologists and forest geneticists to integrate individual tree-level
      dendrophenotypes in genetic association studies.

PMID- 29443423
TI  - Regioselective C-H Alkylation via Carboxylate-Directed Hydroarylation in Water.
AB  - In the presence of catalytic [RuCl2 (p-cym)]2 and using Li3 PO4 as the base,
      benzoic acids react with olefins in water to afford the corresponding 2
      alkylbenzoic acids in moderate to excellent yields. This C-H alkylation process
      is generally applicable to diversely substituted electron-rich and electron
      deficient benzoic acids, along with alpha,beta-unsaturated olefins including
      unprotected acrylic acid. The widely available carboxylate directing group can be
      removed or utilized for further derivatization. Mechanistic investigations
      revealed that the transformation proceeds via a ruthenacycle intermediate.

PMID- 29443424
TI  - CCL23 is a promising biomarker of injury in patients with ischaemic stroke.

PMID- 29443425
TI  - Long-Term Atherosclerotic Vascular Disease Risk and Prognosis in Elderly Women
      With Abdominal Aortic Calcification on Lateral Spine Images Captured During Bone
      Density Testing: A Prospective Study.
AB  - Lateral spine images are captured using bone densitometers for vertebral fracture
      assessment (VFA) in older women. Abdominal aortic calcification (AAC) is commonly
      seen on these images; however, the long-term prognosis in women with AAC remains
      uncertain. In a prospective study of 1052 community-dwelling ambulant white women
      over 70 years old abdominal aortic calcification 24 scale (AAC24) scores were
      calculated from digital lateral spine images captured during bone density testing
      in 1998 or 1999. Cardiovascular risk factors were assessed in 1998, whereas 14.5
      year atherosclerotic vascular disease (ASVD)-related hospitalizations and deaths
      (events) were available through linked health records. Using established cut
      points for AAC 471 women (45%) had low AAC (AAC24 score 0 or 1), 387 (37%)
      moderate AAC (AAC24 score 2-5), and 197 (19%) had high AAC (AAC24 score >=6).
      Over 14.5 years, 420 women experienced an ASVD event. Increasing severity of AAC
      was associated with increased absolute risk of ASVD events (37%, 39%, and 49%,
      respectively, p = 0.008 for trend), ASVD deaths (15%, 21%, and 27%, respectively,
      p < 0.001 for trend), and all-cause mortality (30%, 38%, and 44%, respectively, p
      < 0.001 for trend). After adjusting for Framingham risk scores, women with high
      AAC had increased relative hazard for ASVD events, HR 1.37 (95% CI, 1.07 to 1.77;
      p = 0.013) compared to women with low AAC. Similarly, women with moderate AAC and
      high AAC had increased relative hazards for ASVD deaths HR 1.41 (95% CI, 1.03 to
      1.94; p = 0.034) and HR 1.80 (95% CI, 1.26 to 2.57; p = 0.001), or any deaths HR
      1.30 (95% CI, 1.03 to 1.64; p = 0.026) and HR 1.53 (95% CI, 1.17 to 2.00; p =
      0.002), compared to women with low AAC. In conclusion, more advanced AAC on
      images captured for VFA is associated with long-term ASVD hospitalizations and
      deaths before and after adjusting for Framingham risk scores. AAC assessment
      could be considered in addition to VFA to identify individuals who may benefit
      for more aggressive cardiovascular primary prevention strategies. (c) 2018
      American Society for Bone and Mineral Research.

PMID- 29443426
TI  - Comprehensive investigation into the interconversion of C-2 diastereomers of
      naringin.
AB  - Naringin is a flavanone that widely presents on daily diet and traditional
      medicinal materials. The ratios of naringin C-2 diastereomers are found different
      in reported samples, thus suspiciously leading to various functions. In this
      study, we measured the interconversion of C-2 diastereomers intensively with
      ultimate high-performance liquid chromatography and circular dichroism spectra.
      We examined the diastereomeric naringins in fresh citrus fruit, Huajuhong
      decoction pieces, and naringin tablet; evaluated the impact of tablet production
      procedures in factory; and monitored the rapid racemization in incubation. The
      results not only confirmed that enzyme, temperature, and pH condition could
      influence the interconversion but also demonstrated that diverse ratios of
      diastereomers showed limited influence on metabolic behaviors of naringin in the
      blood, which consequently cause comparable bioactivities. This study could
      provide comprehensive understanding of diastereomeric interconversion and provide
      useful reference for drug development.

PMID- 29443427
TI  - Intravenous immunoglobulins for rituximab-resistant mucous membrane pemphigoid.

PMID- 29443428
TI  - Organocatalytic C-F Bond Activation with Alanes.
AB  - Hydrodefluorination reactions (HDF) of per- and polyfluorinated olefins and
      arenes by cheap aluminum alkyl hydrides in non-coordinating solvents can be
      catalyzed by O and N donors. TONs with respect to the organocatalysts of up to 87
      have been observed. Depending on substrate and concentration, high selectivities
      can be achieved. For the prototypical hexafluoropropene, however, low
      selectivities are observed (E/Z~2). DFT studies show that the preferred HDF
      mechanism for this substrate in the presence of donor solvents proceeds from the
      dimer Me4 Al2 (MU-H)2 ?THF by nucleophilic vinylic substitution (SN V)-like
      transition states with low selectivity and without formation of an intermediate,
      not via hydrometallation or sigma-bond metathesis. In the absence of donor
      solvents, hydrometallation is preferred but this is associated with inaccessibly
      high activation barriers at low temperatures. Donor solvents activate the
      aluminum hydride bond, lower the barrier for HDF significantly, and switch the
      product preference from Z to E. The exact nature of the donor has only a minimal
      influence on the selectivity at low concentrations, as the donor is located far
      away from the active center in the transition states. The mechanism changes at
      higher donor concentrations and proceeds from Me2 AlH?THF via SN V and formation
      of a stable intermediate, from which elimination is unselective, which results in
      a loss of selectivity.

PMID- 29443429
TI  - Electronic circular dichroism for the detection of microalbuminuria.
AB  - Over the past decades, chiroptical spectroscopy has proved its incomparable
      ability to elucidate the structure and spatial arrangement of chiral molecules.
      Systematic analysis of biomolecules in the natural environment of biofluids,
      however, remains challenging. In this study, we used chiroptical spectroscopy to
      monitor urinary levels of human serum albumin. Not only severe proteinuria but
      even just a slightly increased urinary excretion of albumin (microalbuminuria)
      may indicate serious health complications, especially for diabetic individuals.
      Given the chiral nature of albumin and its typical spectral pattern, it may be
      easily observable by chiroptical spectroscopy, particularly electronic circular
      dichroism. The performed chiroptical analysis of urine not only allowed the
      detection of clinically confirmed microalbuminuria but was also able to reveal
      this pathological condition in cases beyond the diagnostic capability of common
      clinical procedures. Thus, our approach suggests that electronic circular
      dichroism is a useful tool for the fast and reliable qualitative monitoring of
      microalbuminuria with the potential for a quantitative analysis in the future.

PMID- 29443430
TI  - Small-Scale Machines Driven by External Power Sources.
AB  - Micro- and nanorobots have shown great potential for applications in various
      fields, including minimally invasive surgery, targeted therapy, cell
      manipulation, environmental monitoring, and water remediation. Recent progress in
      the design, fabrication, and operation of these miniaturized devices has greatly
      enhanced their versatility. In this report, the most recent progress on the
      manipulation of small-scale robots based on power sources, such as magnetic
      fields, light, acoustic waves, electric fields, thermal energy, or combinations
      of these, is surveyed. The design and propulsion mechanism of micro- and
      nanorobots are the focus of this article. Their fabrication and applications are
      also briefly discussed.

PMID- 29443431
TI  - Sarcomas of the sinonasal tract.
AB  - BACKGROUND: Sinonasal sarcomas are rare and heterogeneous in nature. Continuously
      collecting data influencing the prognosis is fundamental for optimizing
      therapeutic assessment of this highly destructive neoplasm. METHODS: We conducted
      a single-institution retrospective cohort study considering 27 patients with
      sinonasal sarcoma. RESULTS: The overall survival (OS) rates for 1 year and 5
      years were calculated as 74% and 36%, respectively. Extent of the primary tumor
      (P = .010), nodal spread (P = .009), and age (P = .004) significantly reduced the
      OS. Disease-free survival (DFS) was significantly reduced by age (P = .003),
      extent of the primary (P = .006), nodal (P = .004), and hematogenous (P = .048)
      spread. Multimodal therapy including surgery improved the OS and DFS rates (P <
      .05). CONCLUSION: Prognosis is poor due to late disease recognition. However,
      multimodal therapeutic regimens, including surgery, may improve the outcome.

PMID- 29443432
TI  - Bioorthogonal Metabolic DNA Labelling using Vinyl Thioether-Modified Thymidine
      and o-Quinolinone Quinone Methide.
AB  - Bioorthogonal metabolic DNA labeling with fluorochromes is a powerful strategy to
      visualize DNA molecules and their functions. Here, we report the development of a
      new DNA metabolic labeling strategy enabled by the catalyst-free bioorthogonal
      ligation using vinyl thioether modified thymidine and o-quinolinone quinone
      methide. With the newly designed vinyl thioether-modified thymidine (VTdT), we
      added labeling tags on cellular DNA, which could further be linked to
      fluorochromes in cells. Therefore, we successfully visualized the DNA
      localization within cells as well as single DNA molecules without other staining
      reagents. In addition, we further characterized this bioorthogonal DNA metabolic
      labeling using DNase I digestion, MS characterization of VTdT as well as VTdT
      oQQF conjugate in cell nuclei or mitochondria. This technique provides a powerful
      strategy to study DNA in cells, which paves the way to achieve future
      spatiotemporal deciphering of DNA synthesis and functions.

PMID- 29443433
TI  - Effects of anodal transcranial direct current stimulation over lower limb primary
      motor cortex on motor learning in healthy individuals.
AB  - Transcranial direct current stimulation (tDCS) is a neuromodulatory technique
      which alters motor functions in healthy humans and in neurological patients. Most
      studies so far investigated the effects of tDCS on mechanisms underlying
      improvements in upper limb performance. To investigate the effect of anodal tDCS
      over the lower limb motor cortex (M1) on lower limb motor learning in healthy
      volunteers, we conducted a randomized, single-blind and sham-controlled study.
      Thirty-three (25.81 +/- 3.85, 14 female) volunteers were included, and received
      anodal or sham tDCS over the left M1 (M1-tDCS); 0.0625 mA/cm2 anodal tDCS was
      applied for 15 min during performance of a visuo-motor task (VMT) with the right
      leg. Motor learning was monitored for performance speed and accuracy based on
      electromyographic recordings. We also investigated the influence of electrode
      size and baseline responsivity to transcranial magnetic stimulation (TMS) on the
      stimulation effects. Relative to baseline measures, only M1-tDCS applied with
      small electrodes and in volunteers with high baseline sensitivity to TMS
      significantly improved VMT performance. The computational analysis showed that
      the small anode was more specific to the targeted leg motor cortex volume when
      compared to the large anode. We conclude that anodal M1-tDCS modulates VMT
      performance in healthy subjects. As these effects critically depend on
      sensitivity to TMS and electrode size, future studies should investigate the
      effects of intensified tDCS and/or model-based different electrode positions in
      low-sensitivity TMS individuals.

PMID- 29443434
TI  - Expanding the Abortion Provider Workforce: A Qualitative Study of Organizations
      Implementing a New California Policy.
AB  - CONTEXT: Access to abortion care in the United States varies according to
      multiple factors, including location, state regulation and provider availability.
      In 2013, California enacted a law that authorized nurse practitioners (NPs),
      certified nurse-midwives (CNMs) and physician assistants (PAs) to provide first
      trimester aspiration abortions; little is known about organizations' experiences
      in implementing this policy change. METHODS: Beginning 10 and 24 months after
      implementation of the new law, semistructured interviews were conducted with 20
      administrators whose five organizations trained and employed NPs, CNMs and PAs as
      providers of aspiration abortions. Interview data on the organizations'
      experiences were analyzed thematically, and facilitators of and barriers to
      implementation were identified. RESULTS: Administrators were committed to the
      provision of aspiration abortions by NPs, CNMs and PAs, and nearly all identified
      improved access to care and complication management as clear benefits of the
      policy change. However, integration of the new providers was uneven and depended
      on a variety of circumstances. Organizational disincentives included financial
      and logistical costs incurred in trying to deploy and integrate the different
      types of providers. Some administrators found that increased costs were
      outweighed by improved patient care, whereas others did not. In general, having a
      strong administrative champion within the organization made a critical
      difference. CONCLUSIONS: California's expansion of the abortion-providing
      workforce had a positive impact on patient care in the sampled organizations.
      However, various organizational obstacles must be addressed to more fully realize
      the benefits of having NPs, CNMs and PAs provide aspiration abortions.

PMID- 29443435
TI  - A Thermally Insulating Textile Inspired by Polar Bear Hair.
AB  - Animals living in the extremely cold environment, such as polar bears, have shown
      amazing capability to keep warm, benefiting from their hollow hairs. Mimicking
      such a strategy in synthetic fibers would stimulate smart textiles for efficient
      personal thermal management, which plays an important role in preventing heat
      loss and improving efficiency in house warming energy consumption. Here, a
      "freeze-spinning" technique is used to realize continuous and large-scale
      fabrication of fibers with aligned porous structure, mimicking polar bear hairs,
      which is difficult to achieve by other methods. A textile woven with such
      biomimetic fibers shows an excellent thermal insulation property as well as good
      breathability and wearability. In addition to passively insulating heat loss, the
      textile can also function as a wearable heater, when doped with electroheating
      materials such as carbon nanotubes, to induce fast thermal response and uniform
      electroheating while maintaining its soft and porous nature for comfortable
      wearing.

PMID- 29443436
TI  - Fitness costs of infection with Serratia symbiotica are associated with greater
      susceptibility to insecticides in the pea aphid Acyrthosiphon pisum.
AB  - BACKGROUND: Aphids are agricultural pests that damage crops by direct feeding and
      by vectoring important plant viruses. Bacterial symbionts can influence aphid
      biology, e.g. by providing essential nutrients or facilitating adaptations to
      biotic and abiotic stress. RESULTS: We investigated the pea aphid (Acyrthosiphon
      pisum Harris) and its commonly associated secondary bacterial symbiont Serratia
      symbiotica to study the effect of this symbiont on host fitness and
      susceptibility to the insecticides imidacloprid, chlorpyrifos methyl, methomyl,
      cyantraniliprole and spirotetramat. There is emerging evidence that members of
      the genus Serratia can degrade and/or detoxify diverse insecticides. Therefore,
      we hypothesized that S. symbiotica may promote resistance to these artificial
      stress agents in aphids. Our results showed that Serratia-infected aphids were
      more susceptible to most of the tested insecticides than non-infected aphids.
      This probably reflects the severe fitness costs associated with S. symbiotica,
      which negatively affects development, reproduction and body weight. CONCLUSION:
      Our study demonstrates that S. symbiotica plays an important role in the ability
      of aphid hosts to tolerate insecticides. These results provide insight into the
      potential changes in tolerance to insecticides in the field because there is a
      continuous and dynamic process of symbiont acquisition and loss that may directly
      affect host biology. (c) 2018 Society of Chemical Industry.

PMID- 29443437
TI  - Influencing Pathways to Quality of Life and HbA1c in Patients With Diabetes: A
      Longitudinal Study That Inform Evidence-Based Practice.
AB  - BACKGROUND: Determining possible associated factors and the influencing pathways
      to hemoglobin A1C (HbA1C) levels and quality of life (QoL) will facilitate the
      development of effective interventions to improve the physical and psychosocial
      health of patients with type 2 diabetes mellitus (T2DM). OBJECTIVES: To test a
      hypothesized model that addressed the pathways among personal characteristics,
      social support, diabetes distress, and self-care behaviors to HbA1C and QoL.
      METHODS: A total of 382 adults with T2DM were recruited. Self-reported
      questionnaires and medical records were used to collect data regarding personal
      characteristics, diabetes distress, and social support at baseline. The self-care
      behaviors characters were collected 6 months later, as well as QoL and HbA1C
      levels 1 year later. RESULTS: The 12-month QoL directly affected 12-month HbA1C
      levels. The 6-month self-care behaviors directly affected 12-month QoL, and
      indirectly affected 12-month HbA1C levels through 12-month QoL. Baseline diabetes
      distress directly affected 12-month QoL. Moreover, baseline diabetes distress
      indirectly affected 12-month HbA1C levels through 12-month QoL. Baseline social
      support directly affected baseline diabetes distress and 6-month self-care
      behaviors. In addition, baseline social support indirectly affected 12-month QoL
      through baseline diabetes distress. Baseline social support also indirectly
      affected 12-month QoL through 6-month self-care behaviors. LINKING EVIDENCE TO
      ACTION: Enhancing QoL is important to improve HbA1C levels. Enhancing self-care
      behaviors is essential to improve subsequent HbA1C control and QoL. Reducing
      diabetes distress is crucial to improve subsequent QoL. Improving social support
      is suggested a favorable strategy to reduce diabetes distress and enhance
      subsequent self-care behaviors in patients with T2DM.

PMID- 29443438
TI  - Obesity is associated with incident atrial fibrillation independent of gender: A
      meta-analysis.
AB  - BACKGROUND: The prevalence of obesity is increasing among the general population.
      Obesity is associated with increased risk of several cardiovascular conditions,
      which in turn may increase the risk for atrial fibrillation (AF). We performed a
      meta-analysis of cohort studies that examined the effect of obesity on the
      incidence of AF. In addition, we examined the effect of obesity on the incidence
      of AF stratified by gender. METHODS AND RESULTS: We searched the MEDLINE and
      EMBASE databases for studies evaluating the effect of obesity on AF. Pooled risk
      ratios (RR) with 95% confidence intervals (CI) were calculated using a random
      effects model. Sixteen trials involving 587,372 subjects were included in the
      analysis. Obesity was defined as body mass index >30 kg/m2 . AF during follow-up
      developed in 5,751 of 91,031 (6.3%) obese subjects and in 15,346 of 496,341
      (3.1%) nonobese subjects (RR = 1.51, 95% CI 1.35 to 1.68; P < 0.00001). Based on
      the pooled estimate across the studies, the effect of obesity on incident AF was
      similar in men (RR = 1.41, 95% 1.24 to 1.62; P < 0.00001) and women (RR = 1.53,
      95% CI 1.19 to 1.97; P < 0.00001). CONCLUSION: Obesity is associated with an
      increased risk of new-onset AF in susceptible individuals. This effect appears to
      be consistent in both genders. Further studies are warranted to examine the
      impact of weight loss interventions on the risk of developing AF.

PMID- 29443439
TI  - Complexity of the Relationships of Pain, Posttraumatic Stress, and Depression in
      Combat-Injured Populations: An Integrative Review to Inform Evidence-Based
      Practice.
AB  - BACKGROUND: Understanding the complex interrelationships between combat injuries,
      physical health, and mental health symptoms is critical to addressing the
      healthcare needs of wounded military personnel and veterans. The relationship
      between injury characteristics, pain, posttraumatic stress disorder (PTSD), and
      depression among combat-injured military personnel is unique to modern conflicts
      and understudied in the nursing literature. AIM: This integrative review
      synthesizes clinical presentations and relationships of combat injury, PTSD,
      depression, and pain in Operation Enduring Freedom (OEF) and Operation Iraqi
      Freedom (OIF) United States military service members and veterans. METHODS: A
      literature search was conducted using relative key terms across databases to
      identify peer-reviewed publications between 2001 and 2016 that examined health
      outcomes of combat-injured persons in OEF and OIF. The quality of evidence was
      evaluated and results synthesized to examine the association of combat injury as
      a risk factor for PTSD, the relationship of PTSD and depression pre- and
      postinjury, and pain management throughout care. RESULTS: Twenty-two articles
      were included in this review. Greater injury and pain severity poses risks for
      developing PTSD following combat injury, while early symptom management lessens
      risks for PTSD. Depression appears to be both a contributing risk factor to
      postinjury PTSD, as well as a comorbidity. LINKING EVIDENCE TO ACTION: Findings
      demonstrate a compelling need for improvements in standardized assessment of pain
      and mental health symptoms across transitions in care. This integrative review
      informs nurse researchers and providers of the clinical characteristics of pain,
      PTSD, and depression following combat injury and offers implications for future
      research promoting optimal surveillance of symptoms.

PMID- 29443440
TI  - Detection of brown adipose tissue by 18 F-FDG PET/CT in
      pheochromocytoma/paraganglioma: A systematic review.

PMID- 29443441
TI  - Cumulative live birth rates and perinatal outcomes with the use of time-lapse
      imaging incubators for embryo culture: a retrospective cohort study of 1882 ART
      cycles.
AB  - OBJECTIVE: Comparison of live birth rates and the perinatal outcomes after fresh
      and frozen embryo transfer between time-lapse imaging (TLI) and standard culture
      (SC) incubators. DESIGN: Retrospective cohort study. SETTING: A single tertiary
      level IVF unit. POPULATION: Women undergoing IVF between January 2014 and October
      2015. METHODS: Comparison was done between 1064 IVF cycles using TLI (TLI cycles)
      and 818 IVF cycles using SC (SC cycles). MAIN OUTCOME MEASURES: Cumulative live
      birth rate per oocyte retrieval and perinatal outcomes including birthweight,
      gestational age, preterm birth (PTB) (<37 weeks), early preterm birth (PTB; <32
      weeks), low birthweight (LBW; <2500 g), very LBW (<1500 g) and macrosomia (>4500
      g). RESULTS: The fresh embryo transfer live birth rate was noted to be higher for
      TLI cycles [TLI 36.8 versus SC 33.9%, adjusted odds ratio (aOR) 1.28, 95% CI 1.05
      1.57], but the frozen embryo transfer live birth rates were not significantly
      different. The mean birthweight was higher in the TLI group after both fresh
      [adjusted mean difference (aMD) 174.78 g, 95% CI 64.80-284.77] and frozen embryo
      transfers (aMD 175.91 g, 95% CI 16.98-334.84). After a fresh embryo transfer,
      there was a lower risk of early PTB and very LBW in the TLI group. Among frozen
      embryo transfers, there was a lower risk of early PTB and LBW in the TLI group.
      CONCLUSIONS: TLI incubators are associated with improved perinatal outcomes and
      higher mean birthweight after fresh and frozen embryo transfer. TWEETABLE
      ABSTRACT: Time-lapse imaging incubators in IVF improve perinatal outcomes after
      both fresh and frozen embryo transfers.

PMID- 29443442
TI  - Paediatric acute disseminated encephalomyelitis followed by optic neuritis:
      disease course, treatment response and outcome.
AB  - BACKGROUND AND PURPOSE: Acute disseminated encephalomyelitis followed by optic
      neuritis (ADEM-ON) is a rare demyelinating syndrome that is different from
      multiple sclerosis and neuromyelitis optica spectrum disorder. The aim of this
      study was to describe the disease course, treatment response and outcome of
      children with ADEM-ON. METHODS: Children of <18 years of age were identified from
      six countries of the EU Paediatric Demyelinating Disease Consortium. Patients
      fulfilled the diagnostic criteria for ADEM followed by at least one ON. Anti
      myelin oligodendrocyte glycoprotein (MOG) antibodies were tested in all patients.
      RESULTS: In this study of 17 patients (nine boys) with ADEM-ON, anti-myelin
      oligodendrocyte glycoprotein (MOG) antibodies were identified in 16 patients. Age
      at onset was 6.1 years (interquartile range, 5.1-9.2 years). Twelve patients
      received oral prednisolone and 10 received maintenance immunosuppression (e.g.
      azathioprine, intravenous immunoglobulins, Rituximab). During a follow-up of 5.3
      years (interquartile range, 1.8-10.2 years), 54 relapses occurred with a median
      of 3 relapses per patient (range, 1-9 per patient). Patients relapsed on all
      treatments but no relapses occurred on a prednisolone dose >10 mg/day. Visual and
      cognitive residual deficits were common in this group. CONCLUSIONS: Acute
      disseminated encephalomyelitis followed by optic neuritis is an anti-MOG antibody
      associated relapsing disorder that can have a heterogeneous disease course.
      Patients were refractory for maintenance immunosuppression and appeared to be
      corticosteroid-dependent. Further international collaborations are now required
      to unify guidelines in this difficult-to-manage group of patients.

PMID- 29443443
TI  - Intermittent response to para-Hisian pacing: A more than paradoxical response.

PMID- 29443444
TI  - Diabetes and intracerebral hemorrhage: baseline characteristics and mortality.
AB  - BACKGROUND AND PURPOSE: Acknowledging the conflicting evidence for diabetes as a
      predictor of short- and long-term mortality following an intracerebral hemorrhage
      (ICH), we compared baseline characteristics and 30-day and long-term mortality
      between patients with and without diabetes after an ICH, paying special attention
      to differences between type 1 (T1D) and type 2 (T2D) diabetes. METHODS: Patients
      with a first-ever ICH were followed for a median of 2.3 years. Adjusting for
      demographics, comorbidities and documented ICH characteristics increasing
      mortality after ICH, logistic regression analysis assessed factors associated
      with case fatality and 1-year survival among the 30-day survivors. Diabetes was
      compared with patients without diabetes in separate models as (i) any diabetes
      and (ii) T1D or T2D. RESULTS: Of our 969 patients, 813 (83.9%) had no diabetes,
      41 (4.2%) had T1D and 115 (11.9%) had T2D. Compared with patients without
      diabetes, those with diabetes were younger, more often men and more frequently
      had hypertension, coronary heart disease and chronic kidney disease, with similar
      ICH characteristics. Patients with T1D were younger, more often had chronic
      kidney disease and brainstem ICH, and less often had atrial fibrillation and
      lobar ICH, than did patients with T2D. Diabetes had no impact on case fatality.
      Any diabetes (odds ratio, 2.57; 1.19-5.52), T1D (odds ratio, 7.04; 1.14-43.48)
      and T2D (odds ratio, 2.32; 1.04-5.17) were independently associated with 1-year
      mortality. CONCLUSIONS: Patients with ICH with diabetes exhibited a distinct
      pattern of comorbidities and disease characteristics with specific differences
      between T1D and T2D. Despite their younger age, T1D seems to carry a
      substantially higher likelihood of long-term mortality after an ICH than does
      T2D.

PMID- 29443445
TI  - Aspirin withdrawal in patients treated with ticagrelor presenting with non-ST
      elevation myocardial infarction.
AB  - : Essentials Strong P2Y12 blockade may cause platelet inhibition that is only
      minimally enhanced by aspirin. We evaluated aspirin withdrawal on platelet
      reactivity in ticagrelor treated patients. Aspirin withdrawal resulted in
      increased platelet reactivity to arachidonic acid. Aspirin withdrawal caused
      little difference in adenosine diphosphate-induced platelet aggregation. SUMMARY:
      Background Recent studies have shown that the thromboxane A2 -dependent pathway
      is dependent on the ADP-P2Y12 pathway, and that strong P2Y12 receptor blockade
      alone causes inhibition of platelet aggregation that is minimally enhanced by
      aspirin. Data from the PLATO trial suggested that, among ticagrelor-treated
      patients, high-dose versus low-dose (< 100 mg day-1 ) aspirin is associated with
      an increased risk fof ischemic events. Objectives To evaluate the impact of
      aspirin withdrawal on platelet reactivity in acute coronary syndrome (ACS)
      patients treated with a potent P2Y12 blocker. Patients/Methods This was a current
      prospective, randomized, placebo-controlled, double-blind, cross-over study. The
      study population comprised 22 consecutive ACS patients who underwent percutaneous
      coronary intervention and were treated with aspirin (100 mg day-1 ) and
      ticagrelor. Thirty days post-ACS, open-label aspirin was stopped, and patients
      were randomized to either blinded aspirin or placebo for 2 weeks, with each
      patient crossing over to the other arm for an additional 2 weeks. Platelet
      reactivity to arachidonic acid and ADP determined with light-transmission
      aggregometry (LTA) and VerifyNow was evaluated at baseline, and 2 weeks and 4
      weeks later. Results Aspirin withdrawal resulted in an increase in arachidonic
      acid induced platelet reactivity as determined with both LTA (77.0% +/- 11.3%
      versus 20.8% +/- 4.4%) and VerifyNow (607.7 +/- 10.6 aspirin reaction units [ARU]
      versus 408.5 +/- 14.4 ARU). Platelet response to ADP, as determined with both LTA
      and VerifyNow, did not differ with either aspirin or placebo (32.9% +/- 2.6%
      versus 35.8% +/- 3.6%, and 33.5 +/- 6.4 P2Y12 reaction units (PRU) versus 29.6 +/
      5.7 PRU, respectively). Conclusions Aspirin withdrawal early post-ACS results in
      increased platelet reactivity in response to arachidonic acid, despite
      concomitant treatment with the potent P2Y12 blocker ticagrelor.

PMID- 29443446
TI  - Diverse Legionella-Like Bacteria Associated with Testate Amoebae of the Genus
      Arcella (Arcellinida: Amoebozoa).
AB  - Diverse species of Legionella and Legionella-like amoebal pathogens (LLAPs) have
      been identified as intracellular bacteria in many amoeboid protists. There are,
      however, other amoeboid groups such as testate amoeba for which we know little
      about their potential to host such bacteria. In this study, we assessed the
      occurrence and diversity of Legionella spp. in cultures and environmental
      isolates of freshwater arcellinid testate amoebae species, Arcella hemispherica,
      Arcella intermedia, and Arcella vulgaris, via 16S rRNA gene sequence analyses and
      fluorescent in situ hybridization (FISH). Analysis of the 16S rRNA gene sequences
      indicated that A. hemispherica, A. intermedia, and A. vulgaris host Legionella
      like bacteria with 94-98% identity to other Legionella spp. based on NCBI BLAST
      search. Phylogenetic analysis placed Legionella-like Arcella-associated bacteria
      (LLAB) in three different clusters within a tree containing all other members of
      Legionella and LLAPs. The intracellular localization of the Legionella within
      Arcella hosts was confirmed using FISH with a Legionella-specific probe. This
      study demonstrates that the host range of Legionella and Legionella-like bacteria
      in the Amoebozoa extends beyond members of "naked" amoebae species, with members
      of the testate amoebae potentially serving an ecological role in the dispersal,
      protection, and replication of Legionella spp. in natural environments.

PMID- 29443447
TI  - Cover crops mitigate direct greenhouse gases balance but reduce drainage under
      climate change scenarios in temperate climate with dry summers.
AB  - Cover crops provide ecosystem services such as storing atmospheric carbon in
      soils after incorporation of their residues. Cover crops also influence soil
      water balance, which can be an issue in temperate climates with dry summers as
      for example in southern France and Europe. As a consequence, it is necessary to
      understand cover crops' long-term influence on greenhouse gases (GHG) and water
      balances to assess their potential to mitigate climate change in arable cropping
      systems. We used the previously calibrated and validated soil-crop model STICS to
      simulate scenarios of cover crop introduction to assess their influence on
      rainfed and irrigated cropping systems and crop rotations distributed among five
      contrasted sites in southern France from 2007 to 2052. Our results showed that
      cover crops can improve mean direct GHG balance by 315 kg CO2 e ha-1  year-1 in
      the long term compared to that of bare soil. This was due mainly to an increase
      in carbon storage in the soil despite a slight increase in N2 O emissions which
      can be compensated by adapting fertilization. Cover crops also influence the
      water balance by reducing mean annual drainage by 20 mm/year but increasing mean
      annual evapotranspiration by 20 mm/year compared to those of bare soil. Using
      cover crops to improve the GHG balance may help to mitigate climate change by
      decreasing CO2 e emitted in cropping systems which can represent a decrease from
      4.5% to 9% of annual GHG emissions of the French agriculture and forestry sector.
      However, if not well managed, they also could create water management issues in
      watersheds with shallow groundwater. Relationships between cover crop biomass and
      its influence on several variables such as drainage, carbon sequestration, and
      GHG emissions could be used to extend our results to other conditions to assess
      the cover crops' influence in a wider range of areas.

PMID- 29443448
TI  - An Intraneural Electrode for Bioelectronic Medicines for Treatment of
      Hypertension.
AB  - OBJECTIVES: As the left vagus nerve (LVN) mediates a baroreflex blood pressure
      (BP) decrease, LVN stimulation (LVNS) could be a therapy for hypertension.
      Moreover, LVNS could elegantly be adjusted to the patient's actual BP and
      physical activity by using the neural information about BP and respiration
      extractable from LVN. However, unselective LVNS will trigger undesirable side
      effects and therefore we here investigated the feasibility of using an
      intraneural electrode for extracting BP and respiration markers from the LVN and
      for selective LVNS. MATERIALS AND METHODS: Experiments were performed on six
      anesthetized pigs from which the BP was recorded using arterial catheters and the
      respiratory cycles by recording the airway pressure. An electrode comprising four
      tripolar channels was inserted longitudinally in the LVN of the animals to
      extract BP and respiration markers from the LVN and for selective LVNS. RESULTS:
      BP-related and respiratory-related neural profiles (BPnPs and RnPs, respectively)
      were derived from at least two electrode channels in all pigs. The BPnPs
      accurately resembled the BP waves and the RnPs accurately resembled the
      respiratory cycles, which suggests that those profiles could serve as BP and
      respiration markers, respectively. The BP was decreased by intraneural LVNS in
      all pigs and in four of those pigs such an effect was induced without major
      cardiac changes through a channel-selective stimulation. CONCLUSION: This study
      shows that it is feasible to extract BP and respiratory markers from the LVN with
      the tested intraneural electrode and suggests that this electrode could also be
      used for selective LVNS.

PMID- 29443449
TI  - Nitrogen-Doped Single Graphene Fiber with Platinum Water Dissociation Catalyst
      for Wearable Humidity Sensor.
AB  - Humidity sensors are essential components in wearable electronics for monitoring
      of environmental condition and physical state. In this work, a unique humidity
      sensing layer composed of nitrogen-doped reduced graphene oxide (nRGO) fiber on
      colorless polyimide film is proposed. Ultralong graphene oxide (GO) fibers are
      synthesized by solution assembly of large GO sheets assisted by lyotropic liquid
      crystal behavior. Chemical modification by nitrogen-doping is carried out under
      thermal annealing in H2 (4%)/N2 (96%) ambient to obtain highly conductive nRGO
      fiber. Very small (~2 nm) Pt nanoparticles are tightly anchored on the surface of
      the nRGO fiber as water dissociation catalysts by an optical sintering process.
      As a result, nRGO fiber can effectively detect wide humidity levels in the range
      of 6.1-66.4% relative humidity (RH). Furthermore, a 1.36-fold higher sensitivity
      (4.51%) at 66.4% RH is achieved using a Pt functionalized nRGO fiber (i.e., Pt
      nRGO fiber) compared with the sensitivity (3.53% at 66.4% RH) of pure nRGO fiber.
      Real-time and portable humidity sensing characteristics are successfully
      demonstrated toward exhaled breath using Pt-nRGO fiber integrated on a portable
      sensing module. The Pt-nRGO fiber with high sensitivity and wide range of
      humidity detection levels offers a new sensing platform for wearable humidity
      sensors.

PMID- 29443450
TI  - Lysine-241 Has a Role in Coupling 2OG Turnover with Substrate Oxidation During
      KDM4-Catalysed Histone Demethylation.
AB  - The JmjC histone lysyl demethylases (KDMs) play important roles in modulating
      histone methylation states and have the potential to be regulated by oxygen
      availability. Lys241 of the KDM4 subfamily is proposed to be important in oxygen
      binding by KDM4A. We report evidence that, although Lys241 is unlikely to be
      directly involved in oxygen binding, it has an important role in coupling 2
      oxoglutarate cosubstrate oxidation with lysine demethylase activity. The results
      suggest that compounds promoting the uncoupling of substrate oxidation are of
      interest as JmjC-KDM inhibitors.

PMID- 29443451
TI  - Use of an autologous bony crossbar graft for the management of caudal septal
      deviation: Our experience in twenty-two patients.

PMID- 29443452
TI  - Development of Versatile Human In Vitro Vascularized Adipose Tissue Model with
      Serum-Free Angiogenesis and Natural Adipogenesis Induction.
AB  - Many adipose tissue-related diseases, such as obesity and type 2 diabetes, are
      worldwide epidemics. For studying these diseases, relevant human cell models are
      needed. In this study, we developed a vascularized adipose tissue model where
      human adipose stromal cells and human umbilical cord vein endothelial cells were
      cocultured with natural adipogenic and defined serum-free angiogenic media for 14
      days. Several different protocols were compared to each other. The protocols
      varied in cell numbers and plating sequences. Lipid accumulation was studied with
      AdipoRed reagent, relative cell number with WST-1 reagent, gene expression of
      glut4, leptin, aP2, adiponectin, PPARgamma and PPARgamma2 with RT-qPCR. Secretion
      of adiponectin, leptin and aP2 was analysed with ELISA. The immunostained
      vascular network was imaged with Cell-IQ and area quantified using ImageJ. In
      this study, both angiogenesis and adipogenesis were successfully induced.
      Protocols produced strong lipid accumulation, good vascular network formation and
      induced adipocyte-specific protein secretion and expression of studied adipocyte
      genes. Results showed that cell numbers and cell plating sequences are important
      factors when aiming at in vitro standardized tissue model. Presence of mature
      vasculature appeared leads to faster the maturation of adipocytes judged by the
      lipid accumulation and gene expression results. The developed vascularized
      adipose tissue model is simple to use, easily modifiable to suit various
      applications and as such, a promising new tool for adipose tissue research when,
      for example, studying the effect of different cell types on adipose tissue
      function or for mechanistic studies.

PMID- 29443453
TI  - Alternative pre-mRNA splicing.

PMID- 29443454
TI  - Voice quality outcomes of idiopathic Parkinson's disease medical treatment: A
      systematic review.
AB  - INTRODUCTION: To investigate voice quality (VQ) impairments in idiopathic
      Parkinson's disease (IPD) and to explore the impact of medical treatments and L
      Dopa challenge testing on voice. METHODS: Relevant studies published between
      January 1980 and June 2017 describing VQ evaluations in IPD were retrieved using
      PubMed, Scopus, Biological Abstracts, BioMed Central and Cochrane databases.
      Issues of clinical relevance, including IPD treatment efficiency and voice
      quality outcomes, were evaluated for each study. The grade of recommendation for
      each publication was determined according to the Oxford Centre for Evidence-Based
      Medicine evidence levels. RESULTS: The database research yielded 106 relevant
      publications, of which 33 studies met the inclusion criteria, for a total of 964
      patients with IPD. Data were extracted by 3 independent physicians who identified
      21, 11 and 1 trials with IIIb, IIb and IIa evidence levels, respectively. The
      main VQ assessment tools used were acoustic testing (N = 27), aerodynamic testing
      (N = 10), subjective measurements (N = 8) and videolaryngostroboscopy (N = 3).
      The majority of trials (N = 32/33) identified subjective or objective VQ
      improvements after medical treatment (N = 10) or better VQ evaluations in healthy
      subjects compared to patients with IPD (N = 22). Especially, our analysis
      supports that VQ overall improves during the L-Dopa challenge testing, making the
      VQ evaluation an additional tool for the IPD diagnosis. The methodology used to
      assess subjective and objective VQ substantially varied from 1 study to another.
      All of the included studies took into consideration the patient's clinical
      profile in the VQ analysis. CONCLUSION: The majority of studies supported that VQ
      assessments remain useful as outcome measures of the effectiveness of medical
      treatment and could be helpful for the IPD diagnosis based on L-Dopa challenge
      testing. Further controlled studies using standardised and transparent
      methodology for measuring acoustic parameters are necessary to confirm the place
      of each tool in both IPD diagnosis and treatment evaluation.

PMID- 29443455
TI  - Isomeric N-Annulated Perylene Diimide Dimers for Organic Solar Cells.
AB  - Two isomeric N-annulated perylene diimide dimers, namely, p-BDNP and m-BDNP were
      designed and synthesized via geometric tuning. The distinct molecular geometry
      and packing arrangements of isomers with almost identical optical and
      electrochemical properties rendered us an in-depth understanding of the molecular
      structure-aggregation state-photovoltaic performance relationship. Blended with
      the commercially available donor PCE-10, p-BDNP and m-BDNP showed distinct
      differences in photovoltaic performance with power conversion efficiencies (PCEs)
      of 5.01 % and 4.15 %, respectively.

PMID- 29443456
TI  - Pharmacokinetics and Safety of Bazedoxifene in Hepatically Impaired and Healthy
      Postmenopausal Women.
AB  - Bazedoxifene, a selective estrogen receptor modulator with proestrogenic effects
      on bone and lipid metabolism and antiestrogenic effects on the breast and
      endometrium, is a treatment option for osteoporosis in postmenopausal women. It
      is extensively metabolized by the liver; therefore, a decrease in liver function
      was expected to decrease bazedoxifene clearance. This single-dose, open-label,
      inpatient/outpatient, nonrandomized study assessed the pharmacokinetics of
      bazedoxifene 20 mg in 18 postmenopausal women with hepatic impairment and 18
      matched healthy postmenopausal women. Bazedoxifene elimination was slower, and
      exposure was higher, in hepatically impaired subjects compared with healthy
      subjects. In subjects with severe (Child-Pugh C) liver impairment, bazedoxifene
      mean half-life was 50% longer than that of healthy subjects. Area under the
      concentration-time curve geometric mean ratios (90%CI) for Child-Pugh A, B, and C
      liver impairment vs healthy subjects were 243% (156-379), 209% (135-326), and
      368% (236-572), respectively. Although there were no severe adverse events in
      this study, bazedoxifene use in patients with hepatic impairment is not
      recommended.

PMID- 29443457
TI  - Cumulative disadvantage: Reply to "Consider choices in the Gender in Science
      debate".

PMID- 29443458
TI  - The functional and psychological burden of empty nose syndrome.
AB  - BACKGROUND: Empty nose syndrome (ENS) is a debilitating disorder thought to arise
      as a postsurgical phenomenon from excessive loss of nasal tissues. Affected
      patients often report a profound impact on all aspects of life, but the extent of
      this burden has not been quantified. We sought to determine the association of
      ENS with mental health and functional impairments. METHODS: A cross-sectional
      study was performed of individuals with ENS recruited from online ENS forums. ENS
      status was validated based on a positive 6-item Empty Nose Syndrome Questionnaire
      (ENS6Q) score and sinus computed tomography imaging or supporting medical
      documentation. Subjects completed the ENS6Q, the 9-item Patient Health
      Questionnaire (PHQ-9) for depression, the 7-item Generalized Anxiety Disorder
      questionnaire (GAD-7), the Epworth Sleepiness Scale for daytime somnolence (ESS),
      the Work Productivity and Impairment questionnaire (WPAI), and the 5-dimension
      EuroQol General Health State Survey (EQ-5D-5L). Pearson correlation analysis was
      performed with alpha = 0.05 to determine significance. RESULTS: Fifty-three ENS
      individuals were included in the study. Overall, participants reported symptoms
      consistent with moderate anxiety (MU = 12.7; standard deviation [SD], 5.9) and
      moderately severe depression warranting treatment (MU = 17.9; SD, 6.8).
      Participants also noted a 62% reduction in productivity at work (n = 24) and 65%
      in all other activities (n = 53). ENS6Q symptom severity was correlated with more
      severe depression (p < 0.001), anxiety (p < 0.001), overall pain/discomfort (p =
      0.002), and impairment in activities of daily living (p = 0.003). CONCLUSION: ENS
      individuals carry a clinically significant psychological burden and experience
      marked difficulties with many activities of daily living. A multimodal approach
      to address the tissue loss with surgery and cognitive-behavioral therapy for the
      psychological burden may provide the most optimal outcome.

PMID- 29443459
TI  - Tunable Bifunctional Activity of Mnx Co3-x O4 Nanocrystals Decorated on Carbon
      Nanotubes for Oxygen Electrocatalysis.
AB  - Noble-metal-free electrocatalysts are attractive for cathodic oxygen catalysis in
      alkaline membrane fuel cells, metal-air batteries, and electrolyzers. However,
      much of the structure-activity relationship is poorly understood. Herein, the
      comprehensive development of manganese cobalt oxide/nitrogen-doped multiwalled
      carbon nanotube hybrids (Mnx Co3-x O4 @NCNTs) is reported for highly reversible
      oxygen reduction and evolution reactions (ORR and OER, respectively). The hybrid
      structures are rationally designed by fine control of surface chemistry and
      synthesis conditions, including tuning of functional groups at surfaces,
      congruent growth of nanocrystals with controllable phases and particle sizes, and
      ensuring strong coupling across catalyst-support interfaces. Electrochemical
      tests reveal distinctly different oxygen catalytic activities among the hybrids,
      Mnx Co3-x O4 @NCNTs. Nanocrystalline MnCo2 O4 @NCNTs (MCO@NCNTs) hybrids show
      superior ORR activity, with a favorable potential to reach 3 mA cm-2 and a high
      current density response, equivalent to that of the commercial Pt/C standard.
      Moreover, the hybrid structure exhibits tunable and durable catalytic activities
      for both ORR and OER, with a lowest overall potential of 0.93 V. It is clear that
      the long-term electrochemical activities can be ensured by rational design of
      hybrid structures from the nanoscale.

PMID- 29443460
TI  - Tracking the Sugar Rush: Incorporating Continuous Glucose Monitoring Into
      Multisite Early Clinical Research With Type 2 Diabetes Subjects.
AB  - Continuous glucose monitoring (CGM) systems allow patients with diabetes mellitus
      to closely track glucose concentrations over several days, identify trends in
      glucose levels, and avoid glucose excursions. This technology has not only
      advanced diabetes mellitus management but has increased patient safety through
      greater glycemic awareness. Due to these attributes, CGM is now being applied in
      therapeutic research as a pharmacodynamic tool to support early clinical drug
      development programs. However, to date only a handful of studies have utilized
      CGM in type 2 diabetes mellitus (T2DM) drug development. A potential barrier from
      fostering greater use of CGM in clinical development may be related to concerns
      over subject variability. Therefore, we investigated a key consideration when
      implementing CGM into early clinical research studies: daily variation within
      patients with T2DM from multiple clinical research units. From 24 patients with
      T2DM, we observed strong daily reproducibility (Pearson R = 0.86, P < .0001) in
      CGM results and found that this technique is practical for multisite studies.
      Altogether, with low daily variability, CGM is a powerful pharmacodynamic tool
      for drug efficacy and safety monitoring.

PMID- 29443462
TI  - Helping hand for melanoma invasion: Transparent zebrafish can catch macrophages
      in the act.

PMID- 29443461
TI  - Genetic sex assignment in wild populations using genotyping-by-sequencing data: A
      statistical threshold approach.
AB  - Establishing the sex of individuals in wild systems can be challenging and often
      requires genetic testing. Genotyping-by-sequencing (GBS) and other reduced
      representation DNA sequencing (RRS) protocols (e.g., RADseq, ddRAD) have enabled
      the analysis of genetic data on an unprecedented scale. Here, we present a novel
      approach for the discovery and statistical validation of sex-specific loci in GBS
      data sets. We used GBS to genotype 166 New Zealand fur seals (NZFS, Arctocephalus
      forsteri) of known sex. We retained monomorphic loci as potential sex-specific
      markers in the locus discovery phase. We then used (i) a sex-specific locus
      threshold (SSLT) to identify significantly male-specific loci within our data
      set; and (ii) a significant sex-assignment threshold (SSAT) to confidently assign
      sex in silico the presence or absence of significantly male-specific loci to
      individuals in our data set treated as unknowns (98.9% accuracy for females;
      95.8% for males, estimated via cross-validation). Furthermore, we assigned sex to
      86 individuals of true unknown sex using our SSAT and assessed the effect of SSLT
      adjustments on these assignments. From 90 verified sex-specific loci, we
      developed a panel of three sex-specific PCR primers that we used to ascertain sex
      independently of our GBS data, which we show amplify reliably in at least two
      other pinniped species. Using monomorphic loci normally discarded from large SNP
      data sets is an effective way to identify robust sex-linked markers for nonmodel
      species. Our novel pipeline can be used to identify and statistically validate
      monomorphic and polymorphic sex-specific markers across a range of species and
      RRS data sets.

PMID- 29443463
TI  - Odanacatib Pharmacokinetics Comparison Between Chinese and Non-Chinese
      Postmenopausal Women.
AB  - Odanacatib (ODN), an oral selective inhibitor of cathepsin K, was an
      investigational agent previously in development for the treatment of
      osteoporosis. In this phase 1 open-label study, 12 healthy Chinese postmenopausal
      women received single-dose ODN 50 mg on day 1 and multiple-dose ODN 50 mg once
      weekly on days 15, 22, 29, and 36 under fasted conditions. Pharmacokinetic (PK)
      parameters were evaluated on days 1 and 36. Multiple-dose area under the
      concentration-time profile (AUC0-168h ) and maximum plasma concentration (Cmax )
      were compared with historical data from 9 non-Chinese postmenopausal women who
      also received ODN 50 mg once weekly for 4 weeks. Median time to Cmax (tmax ) was
      3 and 4 hours following single- and multiple-dose administration, respectively.
      The arithmetic mean +/- SD terminal half-life was 81.0 +/- 14.0 and 106.7 +/-
      14.4 hours following single- and multiple-dose administration, respectively.
      Comparison of multiple-dose PK parameters showed that the geometric mean ratios
      (Chinese/non-Chinese) and 95%CIs for AUC0-168h and Cmax were 0.81 (0.55-1.19) and
      0.87 (0.69-1.11), respectively. All adverse events were mild, none were serious,
      and none led to discontinuation. Single- and multiple-dose PKs of ODN 50 mg in
      Chinese postmenopausal women were generally similar to those previously reported
      in non-Chinese postmenopausal women.

PMID- 29443464
TI  - Identification of a novel HLA-A*33 allele, HLA-A*33:138.
AB  - HLA-A*33:138 differs from A*33:03:01 by a single nucleotide substitution at
      position 523 of exon 3.

PMID- 29443466
TI  - Global and Public Health Issues of 2016.

PMID- 29443467
TI  - Aspects of Global Health Issues: Diseases, Natural Disasters, and Pharmaceutical
      Corporations and Medical Research.
AB  - Global health issues are concerns of all public health officials throughout the
      world. This entails reviewing aspects such as the impact of poverty and the lack
      of access to quality health care, ignored global killers such as Diseases
      (Infectious diseases-Malaria, HIV/AIDS), Natural Disasters (Earthquakes,
      Tsunamis, Floods, and Armed Conflict), Health in the Media, and the Involvement
      of Pharmaceutical Corporations and Medical Research. These issues are challenges
      to many needless deaths. Global initiatives are not advancing as they should,
      such as access to drugs and medications, which some are political.

PMID- 29443468
TI  - Perception of Obesity in the Latino Population: Implications for Weight Loss
      Clinical Trials.
AB  - Ethnic minorities in the United States have a higher prevalence of obesity, with
      higher levels reported in Latinos/Hispanics. A qualitative study was done to
      understand perceptions of obesity and identify factors that may enhance the
      attractiveness of a behavioral weight-loss intervention in the Latino community.
      Weight loss trials designed to target the Latino/Hispanic population may benefit
      by considering the Latino/Hispanic perception of the problem, the barriers to
      weight loss, and for study participation that may be specific to this population.

PMID- 29443469
TI  - Think Like a Nurse: A Critical Thinking Initiative.
AB  - Critical thinking is essential in the practice of the nurse generalist, today.
      Nursing faculty is frequently trying to identify teaching strategies in promoting
      critical thinking and engaging students in active learning. To close the gap
      between critical thinking and student success, a school in the south east United
      States implemented the use of the 'think like a nurse initiative" for incoming
      junior nursing students. Faculty collaborated to adopt the fundamental and
      essential nursing concepts for nursing students to support thinking like a nurse.

PMID- 29443470
TI  - Acculturation and Health Behaviors of African Immigrants Living in the United
      States: An Integrative Review.
AB  - This research was conducted to identify the acculturation and health behaviors in
      the African Immigrant population, which is presently living in the United States.
      Ten studies met the criteria and included health behaviors of status, access to
      health care, psychiatric services, prostate cancer, morbidity and mortality, HIV
      knowledge and beliefs, perceptions of suicide, smoking, and obesity.
      Acculturation was measured using the most common social constructs that
      influenced the health behaviors of nativity, English (language proficiency), age
      at immigration, education and socioeconomic status, religion, age at immigration,
      and length of stay in the U.S. More research is needed to assist in prioritizing
      the health conditions that need intervention in serving this particular
      population.

PMID- 29443471
TI  - Factors Influencing Risk of Homelessness among Youth in Transition from Foster
      Care in Oklahoma: Implications for Reforming Independent Living Services and
      Opportunities.
AB  - Research suggests that youth aging out of foster care may be at higher risk of
      experiencing homelessness than other youth. Among this already at-risk population
      there may be certain characteristics that further exacerbate the risk. This paper
      uses data collected from various local and state agencies to further examine
      significant predictors of homelessness among youth who have aged out of foster
      care.

PMID- 29443472
TI  - Housing Trajectories for Youth Transitioning from Foster Care: Gender Differences
      from 2010-2014.
AB  - This study focuses on longitudinal housing trends for males and females among
      transitional youth who were participants of a transitional living program (2010
      to 2014). Results indicate that young women were more likely to transition to
      secure independent housing than young men. Demographic characteristics,
      education, and employment predicted time to secure independent housing.
      Additionally, results indicate that more highly educated young women transitioned
      to independence at a faster rate than young men with lower education status.

PMID- 29443473
TI  - Economic Well-Being and Independent Living in FosterYouth: Paving the Road to
      Effective Transitioning out of Care.
AB  - Using a mixed-methods methodological approach, the proposed study examines the
      associations between economic well-being and independent living experiences in
      foster youth. Quantitative data were collected from N = 294 in-care foster youth
      using the Casey Life Skills assessment (alpha = .79 to alpha = .95). Qualitative
      data were collected via focus groups with aged-out foster youth (N =15). Results
      provide important insights on youth's economic well-being, financial literacy,
      individual experiences regarding aging out of foster care and independent living.
      This study provides new insights into the complex dynamics of successfully
      transitioning out of foster care and the need for supporting economic well-being
      in foster youth to better prepare them to live independently and develop coping
      skills for the challenges they might experience once they leave the system.

PMID- 29443474
TI  - Partnering to Leverage Multiple Data Sources: Preliminary Findings from a
      Supportive Housing Impact Study.
AB  - This article presents preliminary findings from an impact study that drew upon
      administrative data collected by city agencies and data collected by a supportive
      housing program for young adults who are aging out of foster care, homeless, or
      at risk of homelessness. Participation in the program was associated with a
      reduction in shelter use and jail stays during the two years after program entry.
      The study demonstrates the benefits of collaboration and the possibilities of
      using administrative data from multiple public agencies to evaluate program
      impacts on young adult outcomes.

PMID- 29443475
TI  - Physically Hazardous Housing and Risk for Child Protective Services Involvement.
AB  - The quality and safety of the home environment is a common focus of Child
      Protective Services (CPS) investigations.Yet little is known about whether such
      conditions influence CPS outcomes. The present study uses a sample of low-income
      families to assess the relative importance of housing conditions and other common
      risk and protective factors associated with child maltreatment. Results show that
      hazardous conditions predict investigated child neglect, but not physical abuse
      or indicated reports.

PMID- 29443476
TI  - Housing Matters for Families: Promising Practices from Child Welfare Agencies.
AB  - There is growing acknowledgement that housing can provide more than shelter, a
      basic need. Housing can also act as a foundation, helping families stay
      together.The provision of housing as a prevention or protective strategy against
      child maltreatment has not been widely used by child welfare agencies. A small
      subset of child welfare agencies across the country, however, is incorporating
      housing into their response to cases of child abuse and neglect. Using
      qualitative data from ongoing studies of HUD's Family Unification Program (FUP)
      and the Children's Bureau supportive housing demonstration for high-need child
      welfare involved families, we describe some of the promising practices agencies
      are implementing and testing. Though evaluations of these programs are not yet
      complete, there is a lot the field can learn from these approaches. This paper
      provides an overview of seven promising strategies: (1) partnering with public
      housing agencies and leveraging resources; (2) assessing the housing needs of
      child welfare involved families; (3) triaging and providing housing resources
      based on needs; (4) providing housing first, not. last; (5) developing housing
      stability plans and shared case plans; (6) screening families into housing,
      rather than screening out; and (7) providing housing search assistance.

PMID- 29443477
TI  - Integrated Solutions for Intertwined Challenges: A Statewide Collaboration in
      Supportive Housing for Child Welfare-Involved Families.
AB  - This paper describes Connecticut's Supportive Housing for Families (SHF) program,
      which is one of five national sites comprising a federally- funded demonstration
      of housing and child welfare. Evaluations of supportive housing (SH)
      interventions are complicated by contextual factors that make it difficult to
      isolate their effects. 'Ihese and other challenges complicate efforts to conduct
      rigorous research and establish external validity, and to date, few studies
      examine the impact of SH interventions for child- welfare involved families. We
      describe retrospectively the development of SHF using. six stages of imple-
      mentation articulated within an implementation science framework, noting both the
      core components of the program and its expansion from a small pilot exploration,
      to a statewide initiative, and now to the center of a systems change effort with
      potential to influence national policy and implementation.

PMID- 29443478
TI  - The Family Unification Program: A Randomized-Controlled Trial of Housing
      Stability.
AB  - The study tests the short-term impact on housing stability of the Family
      Unification Program (FUP), a permanent housing program for child welfare-
      involved families at risk of separation from children due to inadequate housing.
      Families eligible for FUP (n = 150) received housing case management services as
      usual, and half were referred for permanent housing vouchers made available
      through FUP. Families referred for FUP secured more enriched home learning
      environments, while more precariously housed families exhibited greater housing,
      stability when referred for FUP. The intervention did not relate with housing
      affordability or improvements in neighborhood quality. Findings suggest benefits
      of FUP-especially for more vulnerable families--in key areas that support child
      developmet; however, families continue to struggle in the context of poverty.

PMID- 29443479
TI  - Family Stability and Child Welfare Involvement among Families Served in Permanent
      Supportive Housing.
AB  - This article examines the effectiveness of supportive housing in fostering family
      preservation and reunification for homeless families with multiple housing
      barriers. Results indicate that more thanhalfofthe supportive housing program
      families who are separated from their families by Child Protective Services prior
      to entering the program are reunified during the 12-month period after entering
      housing. The rate of reunification for supportive housing families is
      significantly higher than the rate for matched families who enter shelters, but
      not significantly different than the rate experienced by matched families
      entering public housing. This study provides encouraging evidence that housing
      for families in the child welfare system, including but necessarily limited to
      supportive housing, can facilitate the reunification of children.

PMID- 29443481
TI  - Trauma Time.

PMID- 29443480
TI  - "To Purify the Dialect of the Tribe." An Essay Review on Two Current Works in the
      Psychoanalytic Field, and Their Bearing on Psychohistory.

PMID- 29443482
TI  - The Psychohistory of Child Maltreatment Among Antebellum Slaveholders: Part II.
AB  - In the psychohistory of the antebellum South, the extent of child abuse in
      slaveholder families is important for understanding how members of the southern
      elite were reared and the extent to which they were infected with the toxic
      residue of their elders' passions and rages. It is argued that the Old South was
      a developing region, rather than an already developed one. Consequently, the rate
      of child abuse that is characteristic of contemporary postindustrial societies is
      not the proper paradigm for conceptualizing the abuse rate in slaveholder
      families. It is proposed instead that the rate of child abuse in contemporary
      developing societies is a better fit for estimating abuse in the antebellum
      South. Societal and familial variables impinging on the abuse of slaveholder
      children-corporal punishment, alcohol consumption, hyper-masculinity, a
      traumatogenic culture of violence, wife abuse, maternal ambivalence and neglect,
      miscegenation and incest are discussed, as is the likelihood of maltreatment by
      slaves. Using a study of child abuse across 28 nations, tentative rates of abuse
      are proposed.

PMID- 29443483
TI  - John Woolman and Ethical Progress in Kitcher's Pragmatic Naturalism.
AB  - The development of John Woolman's views on slavery plays an important evidentiary
      role in Philip Kitcher's recent book, The ethical project (Kitcher 2011). In this
      work Kitcher takes what he calls a "pragmatic naturalist" approach to ethics and
      claims that the discovery of ethical truth plays no role in the emergence of
      ethical progress. To support his view, he argues that Woolman's contribution was
      not due to his discovery of an ethical truth about slavery, not previously known,
      but due to his sensitivity to slavery and his influence on others, which
      contributed to collective progressive change in moral norms involving slavery.
      While not disputing Kitcher's ethical theory, I argue that personal discoveries
      of a moral psychological nature made by Woolman served both as insights and
      motivations for his contribution. Thus, even if there are no such things as
      independent ethical truths that can be discovered by individuals, a fully
      naturalistic approach to ethical progress requires that we make room not only for
      group-level progressive evolution of norms, but also for individual discoveries
      of a moral psychological nature that can sometimes cause an individual to play a
      significant initiating role in progressive ethical transitions that occur at a
      group level.

PMID- 29443484
TI  - Youth self-report of child maltreatment in representative surveys: a systematic
      review.
AB  - INTRODUCTION: This systematic review identified population-representative youth
      surveys containing questions on self-reported child maltreatment. Data quality
      and ethical issues pertinent to maltreatment data collection were also examined.
      METHODS: A search was conducted of relevant online databases for articles
      published from January 2000 through March 2016 reporting on population
      representative data measuring child maltreatment. Inclusion criteria were
      established a priori; two reviewers independently assessed articles to ensure
      that the criteria were met and to verify the accuracy of extracted information.
      RESULTS: A total of 73 articles reporting on 71 surveys met the inclusion
      criteria. A variety of strategies to ensure accurate information and to mitigate
      survey participants' distress were reported. CONCLUSION: The extent to which
      efforts have been undertaken to measure the prevalence of child maltreatment
      reflects its perceived importance across the world. Data on child maltreatment
      can be effectively collected from youth, although our knowledge of best practices
      related to ethics and data quality is incomplete.

PMID- 29443485
TI  - Effectiveness of the CANRISK tool in the identification of dysglycemia in First
      Nations and Metis in Canada.
AB  - INTRODUCTION: First Nations/Metis populations develop diabetes earlier and at
      higher rates than other Canadians. The Canadian diabetes risk questionnaire
      (CANRISK) was developed as a diabetes screening tool for Canadians aged 40 years
      or over. The primary aim of this paper is to assess the effectiveness of the
      existing CANRISK tool and risk scores in detecting dysglycemia in First
      Nations/Metis participants, including among those under the age of 40. A
      secondary aim was to determine whether alternative waist circumference (WC) and
      body mass index (BMI) cut-off points improved the predictive ability of logistic
      regression models using CANRISK variables to predict dysglycemia. METHODS:
      Information from a self-administered CANRISK questionnaire, anthropometric
      measurements, and results of a standard oral glucose tolerance test (OGTT) were
      collected from First Nations and Metis participants (n = 1479). Sensitivity and
      specificity of CANRISK scores using published risk score cut-off points were
      calculated. Logistic regression was conducted with alternative ethnicity-specific
      BMI and WC cut-off points to predict dysglycemia using CANRISK variables.
      RESULTS: Compared with OGTT results, using a CANRISK score cut-off point of 33,
      the sensitivity and specificity of CANRISK was 68% and 63% among individuals aged
      40 or over; it was 27% and 87%, respectively among those under 40. Using a lower
      cut-off point of 21, the sensitivity for individuals under 40 improved to 77%
      with a specificity of 44%. Though specificity at this threshold was low, the
      higher level of sensitivity reflects the importance of the identification of high
      risk individuals in this population. Despite altered cut-off points of BMI and
      WC, logistic regression models demonstrated similar predictive ability.
      CONCLUSION: CANRISK functioned well as a preliminary step for diabetes screening
      in a broad age range of First Nations and Metis in Canada, with an adjusted
      CANRISK cutoff point for individuals under 40, and with no incremental
      improvement from using alternative BMI/WC cut-off points.

PMID- 29443487
TI  - John F. Kennedy, Jr. and the Torn Self: A Psychological Portrait.
AB  - John F. Kennedy, Jr., (1960-1999) was one of the most recognizable figures of the
      2nd half of the 20th century. He died tragically in an airplane he was piloting
      on route to Hyannis Port, Massachusetts to attend the wedding of his cousin, Rory
      Kennedy. Though much has been written about the life of J.F.K., Jr., this article
      represents the first psychobiographical portrait of the iconic personality.
      Employing a multi-theoretical approach to psychobiography, this profile
      integrates psychodynamic theory (James 1902/1982, Winnicott 1965), psychosocial
      development theory (Erikson 1950, 1980), and a modern theory of emerging
      adulthood (Arnett 2004) to develop a deep psychological portrait of the beloved
      son of President John F. Kennedy and Jacqueline Kennedy Onassis. J.F.K., Jr.'s
      life is traced along the four developmental periods of infancy and childhood,
      high school and college, emerging adulthood, and young adulthood. Psychobiography
      often focuses on unsolved mysteries in the lives of historic figures, and this
      profile of J.F.K., Jr., explores his search for his unique identity, whether he
      would have entered political life, and the likely future of his life with Carolyn
      Bessette Kennedy had they lived.

PMID- 29443486
TI  - Effects on patients of variations in the implementation of a cardiometabolic risk
      intervention program in Montreal.
AB  - INTRODUCTION: In 2011, the Agence de la sante et des services sociaux de Montreal
      (ASSSM), in partnership with the region's Centres de sante et de services sociaux
      (CSSS), coordinated the implementation of a program on cardiometabolic risk based
      on the Chronic Care Model. The program, intended for patients suffering from
      diabetes or hypertension, involved a series of individual follow-up appointments,
      group classes and exercise sessions. Our study assesses the impact on patient
      health outcomes of variations in the implementation of some aspects of the
      program among the six CSSSs taking part in the study. METHODS: The evaluation was
      carried out using a quasi-experimental "before and after" design. Implementation
      variables were constructed based on data collected during the implementation
      analysis regarding resources, compliance with the clinical process set out in the
      regional program, the program experience and internal coordination within the
      care team. Differences in differences using propensity scores were calculated for
      HbA1c results, achieving the blood pressure (BP) target, and two lifestyle
      targets (exercise level and carbohydrate distribution) at the 6- and 12-month
      follow-ups, based on greater or lesser patient exposure to the implementation of
      various aspects of the program under study. RESULTS: The results focus on 1185
      patients for whom we had data at the 6-month follow- up and the 992 patients from
      the 12-month follow-up. The difference in differences analysis shows no clear
      association between the extent of implementation of the various aspects of the
      program under study and patient health outcomes. CONCLUSION: The program produces
      effects on selected health indicators independent of variations in program
      implementation among the CSSSs taking part in the study. The results suggest that
      the effects of this type of program are more highly dependent on the delivery of
      interventions to patients than on the organizational aspects of its
      implementation.

PMID- 29443488
TI  - Critical Controversies in Psychoanalysis: the Contributions of Arnold D.
      Richards.

PMID- 29443489
TI  - The Psychology of Religion Today.

PMID- 29443490
TI  - Orthogonally Aligned Block Copolymer Line Patterns on Minimal Topographic
      Patterns.
AB  - We demonstrate the generation of block copolymer (BCP) line patterns oriented
      orthogonal to a very small (minimal) topographic trench pattern over arbitrarily
      large areas using solvent-vapor annealing. Increasing the thickness of BCP films
      induced an orthogonal alignment of the BCP cylindrical microdomains, where full
      orthogonal alignment of the cylindrical microdomains with respect to the trench
      direction was obtained at a film thickness corresponding to 1.70 L0. A capillary
      flow of the solvent across the trenches was a critical factor in the alignment of
      the cylindrical microdomains. Grazing incidence small-angle X-ray scattering was
      used to determine the orientation function of the microdomains, with a value of
      0.997 being found reflecting a nearly perfect orientation. This approach to
      produce orthogonally aligned BCP line patterns could be extended to the
      nanomanufacturing and fabrication of hierarchical nanostructures.

PMID- 29443491
TI  - Suppression of Cation Segregation in (La,Sr)CoO3-delta by Elastic Energy
      Minimization.
AB  - Strontium segregation at perovskite surfaces deteriorates the oxygen reduction
      reaction kinetics of cathodes and therefore the long-term stability of solid
      oxide fuel cells (SOFCs). For the systematic and quantitative assessment of the
      elastic energy in perovskite oxides, which is known to be one of the main origins
      for dopant segregation, we report the fractional free volume as a new descriptor
      for the elastic energy in the perovskite oxide system. To verify the fractional
      free volume model, three samples were prepared with different A-site dopants:
      La0.6Sr0.4CoO3-delta, La0.6Sr0.2Ca0.2CoO3-delta, and La0.6Ca0.4CoO3-delta. A
      combination of the theoretical calculations of the segregation energy and oxide
      formation energy and experimental measurements of the structural, chemical, and
      electrochemical degradation substantiated the validity of using the fractional
      free volume to predict the dopant segregation. Furthermore, the dopant
      segregation could be significantly suppressed by increasing the fractional free
      volume in the perovskite oxides with dopant substitution. Our results provide
      insight into dopant segregation from the elastic energy perspective and offer a
      design guideline for SOFC cathodes with enhanced stability at elevated
      temperatures.

PMID- 29443492
TI  - Atomic Layer Deposition of Nickel Carbide from a Nickel Amidinate Precursor and
      Hydrogen Plasma.
AB  - A new atomic layer deposition (ALD) process for depositing nickel carbide (Ni3C
      x) thin films is reported, using bis( N, N'-di- tert
      butylacetamidinato)nickel(II) and H2 plasma. The process shows a good layer-by
      layer film growth behavior with a saturated film growth rate of 0.039 nm/cycle
      for a fairly wide process temperature window from 75 to 250  degrees C.
      Comprehensive material characterizations are performed on the Ni3C x films
      deposited at 95  degrees C with various H2 plasma pulse lengths from 5 to 12 s,
      and no appreciable difference is found with the change of the plasma pulse
      length. The deposited Ni3C x films are fairly pure, smooth, and conductive, and
      the x in the nominal formula of Ni3C x is approximately 0.7. The ALD Ni3C x films
      are polycrystalline with a rhombohedral Ni3C crystal structure, and the films are
      free of nanocrystalline graphite or amorphous carbon. Last, we demonstrate that,
      by using this ALD process, highly uniform Ni3C x films can be conformally
      deposited into deep narrow trenches with an aspect ratio as high as 20:1, which
      thereby highlights the broad and promising applicability of this process for
      conformal Ni3C x film coatings on complex high-aspect-ratio 3D architectures in
      general.

PMID- 29443493
TI  - Scalable Inkjet-Based Structural Color Printing by Molding Transparent Gratings
      on Multilayer Nanostructured Surfaces.
AB  - To enable customized manufacturing of structural colors for commercial
      applications, up-scalable, low-cost, rapid, and versatile printing techniques are
      highly demanded. In this paper, we introduce a viable strategy for scaling up
      production of custom-input images by patterning individual structural colors on
      separate layers, which are then vertically stacked and recombined into full-color
      images. By applying this strategy on molded-ink-on-nanostructured-surface
      printing, we present an industry-applicable inkjet structural color printing
      technique termed multilayer molded-ink-on-nanostructured-surface (M-MIONS)
      printing, in which structural color pixels are molded on multiple layers of
      nanostructured surfaces. Transparent colorless titanium dioxide nanoparticles
      were inkjet-printed onto three separate transparent polymer substrates, and each
      substrate surface has one specific subwavelength grating pattern for molding the
      deposited nanoparticles into structural color pixels of red, green, or blue
      primary color. After index-matching lamination, the three layers were vertically
      stacked and bonded to display a color image. Each primary color can be printed
      into a range of different shades controlled through a half-tone process, and full
      colors were achieved by mixing primary colors from three layers. In our
      experiments, an image size as big as 10 cm by 10 cm was effortlessly achieved,
      and even larger images can potentially be printed on recombined grating surfaces.
      In one application example, the M-MIONS technique was used for printing
      customizable transparent color optical variable devices for protecting
      personalized security documents. In another example, a transparent diffractive
      color image printed with the M-MIONS technique was pasted onto a transparent
      panel for overlaying colorful information onto one's view of reality.

PMID- 29443494
TI  - Macrophage-Instructed Intracellular Staphylococcus aureus Killing by Targeting
      Photodynamic Dimers.
AB  - The survival of Staphylococcus aureus inside phagocytes is considered to be the
      sticking point of long-term chronic inflammation. Here, we fabricate peptide
      chlorophyll-based photodynamic therapy (PDT) agents with "sandwich" dimeric
      structure to enhance the PDT effect and active targeting property to eliminate
      intracellular infections, which could be seen as prospective antibacterial agents
      for inflammation.

PMID- 29443495
TI  - Dynamic Sliding Enhancement on the Friction and Adhesion of Graphene, Graphene
      Oxide, and Fluorinated Graphene.
AB  - Graphene and functionalized graphene are promising candidates as ultrathin solid
      lubricants for dealing with the adhesion and friction in micro- and
      nanoelectromechanical systems (MEMS and NEMS). Here, the dynamic friction and
      adhesion characteristics of pristine graphene (PG), graphene oxide (GO), and
      fluorinated graphene (FG) were comparatively studied using atomic force
      microscopy (AFM). The friction as a function of load shows nonlinear
      characteristic on GO with strong adhesion and linear characteristic on PG and FG
      with relatively weak adhesions. An adhesion enhancement phenomenon that the slide
      off force after dynamic friction sliding is larger than the pull-off force is
      observed. The degree of adhesion enhancement increases with the increasing
      surface energy, accompanied by a corresponding increase in transient friction
      strengthening effect. The dynamic adhesion and friction enhancements are
      attributed to the coupling of dynamic tip sliding and surface hydrophilic
      properties. The atomic-scale stick-slip behaviors confirm that the interfacial
      interaction is enhanced during dynamic sliding, and the enhancing degree depends
      on the surface hydrophilic properties. These findings demonstrate the adhesive
      strength between the contact surfaces can be enhanced in the dynamic friction
      process, which needs careful attention in the interface design of MEMS and NEMS.

PMID- 29443496
TI  - Inert C-H Bond Transformations Enabled by Organometallic Manganese Catalysis.
AB  - Traditional organic synthesis relies heavily on the transformations of various
      preinstalled functional groups, such as cross-coupling reactions using
      organohalides and organometallic reagents. The strategy of C-H activation enables
      the direct formation of C-C/C-X (X = heteroatom) bonds from inert C-H bonds,
      which can enhance the atom- and step-economy of organic synthesis. To date,
      precious metals have overwhelmingly dominated the C-H activation field; however,
      the rarity and high cost of these metals necessitate the development of more
      sustainable catalysts. In this regard, catalysts based on manganese are highly
      desirable owing to the abundant reserve of manganese in the earth's crust and its
      economic benefits, low toxicity, and potentially unique reactivity. Although the
      first stoichiometric manganese-mediated C-H activation reaction was reported as
      early as 1970, manganese-catalyzed C-H activation reactions are largely
      underdeveloped. How to construct an efficient catalytic cycle for manganese in C
      H activation reactions remains as a key issue to be addressed. In this Account,
      we summarize our recent advances in the manganese-catalyzed transformations of
      inert C-H bonds. To overcome the challenges associated with building manganese
      based catalytic cycles, we developed two novel strategies, namely, synergy
      between manganese catalysts and bases and between manganese catalysts (with or
      w/o bases) and acids. By implementing the former strategy, we developed
      cooperative manganese/base catalytic systems that facilitate a new mode of C-H
      bond activation by manganese via a redox-neutral base-assisted deprotonation
      mechanism. As such, the requirement for the tedious preparation of MnR(CO)5
      complexes (R = Me, Bn, Ph) in stoichiometric reactions was eliminated, and a
      series of manganese-catalyzed C-H activation reactions of arenes with various
      reaction partners having C=C and C?C bonds were achieved. Through the latter
      strategy of synergy between manganese catalysts (with or w/o bases) and acids, we
      disclosed a "dual activation" mode for performing manganese-catalyzed C-H bond
      transformations, that is, merging C-H activation by manganese catalysts and C-X
      multiple bond activation by Lewis acids. Consequently, the scope of C-H
      substrates could be expanded to include challenging ketones and olefinic C-H
      compounds. Additionally, the range of reaction partners could be significantly
      broadened to include those bearing more polarized C?O, C?N, and C=N bonds such as
      aldehydes, imines, and nitriles. Remarkably, the innate reactivity of different C
      H bonds in ketones could be reversed by manganese catalysis, and the reactions
      could even be carried out at room temperature. Our findings provide guiding
      information for the future development of manganese-catalyzed C-H activation
      reactions and beyond. Related important contributions from other groups are
      mentioned, and the remaining challenges and future perspective in this emerging
      area are also presented.

PMID- 29443497
TI  - Prediction of Drug-Induced Nephrotoxicity with a Hydroxyl Radical and Caspase
      Light-Up Dual-Signal Nanoprobe.
AB  - The development of well-designed nanoprobes for specific imaging of multiple
      biomarkers in renal cells will afford beneficial information related to the
      transmutation process of drug-induced kidney injury (DIKI). However, the most
      reported nanoprobes for DIKI detection were dependent on single-signal output and
      lack of kidney targeting. In this work, we reported a renal cell targeting and
      dual-signal nanoprobe by encapsulating Brite 670 and Dabcyl-KFFFDEVDK-FAM into a
      low molecular weight chitosan nanoparticle. Confocal fluorescence imaging results
      demonstrated that the nanoprobe could visualize the upregulation of hydroxyl
      radical in early stage and activation of caspase-3 in late stage of DIKI at both
      the renal cell and tissue level. In a mouse DIKI model, the positive time of 8 h
      using nanoprobe imaging was superior to that of 72 h for serum creatinine or
      blood urea nitrogen, 16 h for cystatin-C, and 24 h for kidney injury molecule-1
      with conventional methods. These results demonstrated that the nanoprobe may be a
      promising tool for effective early prediction and discriminative imaging of DIKI.

PMID- 29443498
TI  - Spectrally Resolved and Functional Super-resolution Microscopy via Ultrahigh
      Throughput Single-Molecule Spectroscopy.
AB  - As an elegant integration of the spatial and temporal dimensions of single
      molecule fluorescence, single-molecule localization microscopy (SMLM) overcomes
      the diffraction-limited resolution barrier of optical microscopy by localizing
      single molecules that stochastically switch between fluorescent and dark states
      over time. While this type of super-resolution microscopy (SRM) technique readily
      achieves remarkable spatial resolutions of ~10 nm, it typically provides no
      spectral information. Meanwhile, current scanning-based single-location
      approaches for mapping the positions and spectra of single molecules are limited
      by low throughput and are difficult to apply to densely labeled (bio)samples. In
      this Account, we summarize the rationale, design, and results of our recent
      efforts toward the integration of the spectral dimension of single-molecule
      fluorescence with SMLM to achieve spectrally resolved SMLM (SR-SMLM) and
      functional SRM ( f-SRM). By developing a wide-field scheme for spectral
      measurement and implementing single-molecule fluorescence on-off switching
      typical of SMLM, we first showed that in densely labeled (bio)samples it is
      possible to record the fluorescence spectra and positions of millions of single
      molecules synchronously within minutes, giving rise to ultrahigh-throughput
      single-molecule spectroscopy and SR-SMLM. This allowed us to first show
      statistically that for many dyes, single molecules of the same species exhibit
      near identical emission in fixed cells. This narrow distribution of emission
      wavelengths, which contrasts markedly with previous results at solid surfaces,
      allowed us to unambiguously identify single molecules of spectrally similar dyes.
      Crosstalk-free, multiplexed SRM was thus achieved for four dyes that were merely
      10 nm apart in emission spectrum, with the three-dimensional SRM images of all
      four dyes being automatically aligned within one image channel. The ability to
      incorporate single-molecule fluorescence measurement with SMLM was next utilized
      to achieve f-SRM. By encoding functional information into the spectral responses
      of environment-sensing fluorescent probes, f-SRM transcends the structural
      information provided by typical SRM techniques and reveals the spatiotemporal
      distribution of physicochemical parameters with single-molecule sensitivity and
      nanoscale spatial resolution. As one example, by employing the solvatochromic dye
      Nile Red to sense local chemical polarity, we revealed nanoscale heterogeneity in
      the membranes of live mammalian cells. This enabled us to unveil substantial
      polarity differences between the plasma membrane and the membranes of nanoscale
      intracellular organelles, a result we determined to be due to differences in
      local cholesterol levels. With the addition of cholesterol or cholera toxin, we
      further observed the formation of low-polarity, raftlike nanodomains in the
      plasma membrane. In another study, we generalized SR-SMLM to fluorogenic single
      molecule reactions. As a wide-field technique, SR-SMLM readily captures the
      emission spectra of individual product fluorescent molecules that are
      stochastically produced from nonfluorescent reactants at random locations over
      large sample areas, and therefore, it provides the unique possibility to
      spectrally identify and characterize single product molecules in a high
      throughput fashion. Using the ring-opening reaction of a photochromic spiropyran
      as an example, we demonstrated that the capability to resolve the emission
      spectra of single product molecules could unveil rich, multipath reaction
      pathways. In summary, by integrating the spatial, temporal, and spectral
      dimensions of single-molecule fluorescence, SR-SMLM and f-SRM add rich spectral
      and functional dimensions to SRM and thus open up new ways of probing biological
      and chemical systems at the single-molecule and nanoscale levels.

PMID- 29443499
TI  - Optical Properties of Reconfigurable Polymer/Silver Nanoprism Hybrids: Tunable
      Color and Infrared Scattering Contrast.
AB  - We synthesize and characterize stimulus-responsive nanocomposites consisting of
      poly( N-isopropylacrylamide) (PNIPAM) with controlled loadings of anisotropic
      plate-like silver nanoprisms. These composites show strong, reversible switching
      of their optical extinction and scattering properties in response to temperature
      cycling. We use UV-vis-NIR spectroscopy and dynamic light scattering to
      characterize the hybrids and show that the loading density of the silver
      nanoprisms in the polymer and the size of the nanoprisms are both factors that
      can be used to tailor the optical response of the composites, extending the range
      of colors beyond that previously reported with PNIPAM/plasmonic nanoparticle
      composites. These PNIPAM/silver nanoprism hybrids exhibit thermochromic shifts
      that are 5-10 times larger than those typically reported for similar structures
      of PNIPAM composites with silver nanoparticles of a comparable range of loading
      density. In addition, we show that these composites can exhibit very large
      ratiometric changes in scattering in the NIR, which could open applications for
      related materials in thermal management and NIR labeling and taggants.

PMID- 29443500
TI  - Bispecific Antibody-Functionalized Upconversion Nanoprobe.
AB  - Upconversion nanoparticles (UCNPs) are new optical probes for biological
      applications. For specific biomolecular recognition to be realized for diagnosis
      and imaging, the key lies in developing a stable and easy-to-use bioconjugation
      method for antibody modification. Current methods are not yet satisfactory
      regarding conjugation time, stability, and binding efficiency. Here, we report a
      facile and high-yield approach based on a bispecific antibody (BsAb) free of
      chemical reaction steps. One end of the BsAb is designed to recognize methoxy
      polyethylene glycol-coated UCNPs, and the other end of the BsAb is designed to
      recognize the cancer antigen biomarker. Through simple vortexing, BsAb-UCNP
      nanoprobes form within 30 min and show higher (up to 54%) association to the
      target than that of the traditional UCNP nanoprobes in the ELISA-like assay. We
      further demonstrate its successful binding to the cancer cells with high
      efficiency and specificity for background-free fluorescence imaging under near
      infrared excitation. This method suggests a general approach broadly suitable for
      functionalizing a range of nanoparticles to specifically target biomolecules.

PMID- 29443501
TI  - Magnetically Actuated Peanut Colloid Motors for Cell Manipulation and Patterning.
AB  - We report a magnetically actuated peanut-shaped hematite colloid motor that can
      not only move in a rolling or wobbling mode in fluids but also perform single
      cell manipulation and patterning in a noncontact way. The peanut motor in a
      rolling mode can reach a maximal velocity of 10.6 MUm s-1 under a rotating
      magnetic field of 130 Hz and 6.3 mT and achieve a more precisely controllable
      motion in predefined tracks. While in a wobbling mode, the motor reaches a
      maximal velocity of 14.5 MUm s-1 under a conical rotating magnetic field of 80 Hz
      and 6.3 mT and can climb over steep slopes to adapt the motor for more complex
      environments. The fluid flow simulation results reveal that the difference
      between two movement modes mostly comes from the distribution discrepancy of the
      flow fields near the motors. Through the integration of the rolling and wobbling
      movement, these peanut motors can autonomously transport and release cells to a
      predefined site and thus form complex cell patterns without a physical contact.
      Such magnetically actuated peanut colloid motors afford a biofriendly technique
      for manipulation and patterning of cells, cell measurements, and intracellular
      communication investigations.

PMID- 29443502
TI  - Direct Classification of GC * GC-Analyzed Complex Mixtures Using Non-Negative
      Matrix Factorization-Based Feature Extraction.
AB  - Complex chemical mixtures need to be evaluated to, for example, aid in medical
      diagnoses, assess product quality, and assess environmental conditions. Two
      dimensional gas chromatography (GC * GC), which is a comprehensive analytical
      technique, combined with data classification techniques, has attracted great
      interest for assessing mixtures. In this study, a nontarget cross-sample analysis
      based unsupervised direct classification method using non-negative matrix
      factorization was developed for assessing mixtures analyzed by GC * GC. The
      method was developed using GC * GC data for more than 30 river water samples as
      image data. The retention time shift correction data processing step was
      important to the classification accuracy because the compound signals were found
      at slightly different times for different samples. The maximum likelihood
      estimates of the matching ratios for the 30 samples, with retention time shift
      correction, were 86.8% and 77.0% using two and three ranks, respectively. The
      method is easy to perform and intuitive, requiring no specific knowledge or
      labeled data. This direct classification method will therefore be particularly
      useful for performing initial screens of large numbers of samples and for
      identifying major differences between samples.

PMID- 29443503
TI  - Dual-Color Bioluminescent Sensor Proteins for Therapeutic Drug Monitoring of
      Antitumor Antibodies.
AB  - Monitoring the levels of therapeutic antibodies in individual patients would
      allow patient-specific dose optimization, with the potential for major
      therapeutic and financial benefits. Our group recently developed a new platform
      of bioluminescent sensor proteins (LUMABS; LUMinescent AntiBody Sensor) that
      allow antibody detection directly in blood plasma. In this study, we targeted
      four clinically important therapeutic antibodies, the Her2-receptor targeting
      trastuzumab, the anti-CD20 antibodies rituximab and obinutuzumab, and the EGFR
      blocking cetuximab. A strong correlation was found between the affinity of the
      antibody binding peptide and sensor performance. LUMABS sensors with
      physiologically relevant affinities and decent sensor responses were obtained for
      trastuzumab and cetuximab using mimotope and meditope peptides, respectively,
      with affinities in the 10-7 M range. The lower affinity of the CD20-derived
      cyclic peptide employed in the anti-CD20 LUMABS sensor ( Kd = 10-5 M), translated
      in a LUMABS sensor with a strongly attenuated sensor response. The trastuzumab
      and cetuximab sensors were further characterized with respect to binding kinetics
      and their performance in undiluted blood plasma. For both antibodies, LUMABS
      based detection directly in plasma compared well to the analytical performance of
      commercial ELISA kits. Besides identifying important design parameters for the
      development of new LUMABS sensors, this work demonstrates the potential of the
      LUMABS platform for point-of-care detection of therapeutic antibodies.

PMID- 29443504
TI  - Ion Source Multiplexing on a Single Mass Spectrometer.
AB  - We present the simple approach for the combination of different ion sources on a
      single mass spectrometer without any interference between them. Each ion source
      can be positioned as far as 1 m from the mass spectrometer; ions are transported
      by the means of flexible copper tubes, which are connected, to the separate inlet
      capillaries. Special valves enable switching channels on and off. Using this
      approach, we successfully combined native electrospray ionization (ESI), regular
      ESI, beta-electrons ionization, and atmospheric pressure photoionization (APPI)
      of thermally desorbed vapors of petroleum on a single mass spectrometer. In
      addition, separate channels allow infusing internal calibration mixture or
      performing ion molecular reactions in one channel and using the other as a
      reference. Using this idea, we have developed an original sequential window
      acquisition of all theoretical mass spectra (SWATH MS) approach in which peptide
      ions are transported in different channels, one of which is heated to high
      temperature so that ions are thermally fragmented, and the other channel ensures
      the presence of nonfragmented ions in the spectrum. Also, we demonstrated the
      possibility to perform gas phase H/D exchange reaction in one channel and using
      another as reference. Use of valves makes it possible to exclude any interference
      between them. Thus, we have demonstrated the possibility to create a multichannel
      system in which ions would be transported through several inlet tubes in which
      different ion molecular reactions such as Paterno-Buchi, ozonation, or H/D
      exchange will occur. Comparison of mass spectra recorded when different channels
      are open will provide structural and chemical information about unknown species.

PMID- 29443505
TI  - Cellulose Depolymerization over Heterogeneous Catalysts.
AB  - Cellulosic biomass is the largest source of renewable organic carbon on our
      planet. Cellulose accounts for 40-50 wt % of this lignocellulose, and it is a
      feedstock for industrially important chemicals and fuels. The first step in
      cellulose conversion involves its depolymerization to glucose or to its
      hydrogenated product sorbitol. The hydrolysis of cellulose to glucose by
      homogeneous mineral acids was the subject of research for almost a century.
      However, homogeneous acids have significant drawbacks and are neither economical
      nor environmentally friendly. In 2006, our group reported for the first time the
      ability of heterogeneous catalysts to depolymerize cellulose through hydrolytic
      hydrogenation to produce sorbitol. Later, we reported the hydrolysis of cellulose
      to glucose using carbon catalyst containing weakly acidic functional groups.
      Understanding the reaction between cellulose and heterogeneous catalyst is a
      challenge as the reaction occurs between a solid substrate and a solid catalyst.
      In this Account, we describe our efforts for the conversion of cellulose to
      sorbitol and glucose using heterogeneous catalysts. Sorbitol is produced by
      sequential hydrolysis and hydrogenation of cellulose in one pot. We reported
      sorbitol synthesis from cellulose in the presence of supported metal catalysts
      and H2 gas. The reducing environment of the reaction prevents byproduct
      formation, and harsh reaction conditions can be used to achieve sorbitol yield of
      up to 90%. Glucose is produced by acid catalyzed hydrolysis of cellulose, a more
      challenging reaction owing to the tendency of glucose to rapidly decompose in hot
      water. Sulfonated carbons were first reported as active catalysts for cellulose
      hydrolysis, but they were hydrothermally unstable under the reaction conditions.
      We found that carbon catalysts bearing weakly acidic functional groups such as
      hydroxyl and carboxylic acids are also active. Weakly acidic functional groups
      are hydrothermally stable, and a soluble sugar yield of 90% was achieved in a 20
      min reaction. We clarified that the polycyclic aromatic surface of the carbon
      adsorbs cellulose molecules on its surface by CH-pi and hydrophobic interactions
      driven by a positive change in entropy of the system. The adsorbed molecules are
      rapidly hydrolyzed by active sites containing vicinal functional groups that
      recognize the hydroxyl groups on cellulose to achieve a high frequency factor.
      This phenomenon is analogous to the hydrolysis of cellulose by enzymes that use
      CH-pi and hydrophobic interactions along with weakly acidic carboxylic acid and
      carboxylate pair to catalyze the reaction. However, in comparison with enzymes,
      carbon catalyst is functional over a wide range of pH and temperatures. We also
      developed a continuous flow slurry process to demonstrate the feasibility for
      commercial application of carbon-catalyzed cellulose hydrolysis to glucose using
      inexpensive catalyst prepared by air oxidation. We believe that further efforts
      in this field should be directed toward eliminating roadblocks for the
      commercialization of cellulose conversion reactions.

PMID- 29443506
TI  - Peptoid Backbone Flexibilility Dictates Its Interaction with Water and Surfaces:
      A Molecular Dynamics Investigation.
AB  - Peptoids are peptide-mimetic biopolymers that are easy to synthesize and
      adaptable for use in drugs, chemical scaffolds, and coatings. However, there is
      insufficient information about their structural preferences and interactions with
      the environment in various applications. We conducted a study to understand the
      fundamental differences between peptides and peptoids using molecular dynamics
      simulations with semiempirical (PM6) and empirical (AMBER) potentials, in
      conjunction with metadynamics enhanced sampling. From studies of single molecules
      in water and on surfaces, we found that sarcosine (model peptoid) is much more
      flexible than alanine (model peptide) in different environments. However, the
      sarcosine and alanine interact similarly with a hydrophobic or a hydrophilic.
      Finally, this study highlights the conformational landscape of peptoids and the
      dominant interactions that drive peptoids toward these conformations.

PMID- 29443507
TI  - Three-Dimensional Directionality Is a Pivotal Structural Feature for the
      Bioactivity of Azabisphosphonate-Capped Poly(PhosphorHydrazone) Nanodrug
      Dendrimers.
AB  - Dendrimers are nanosized, nonlinear, hyperbranched polymers whose overall 3D
      shape is key for their biological activity. Poly(PhosphorHydrazone) (PPH)
      dendrimers capped with aza-bisphosphonate (ABP) end groups are known to have anti
      inflammatory properties enabling the control of inflammatory diseases in
      different mouse models. Here we screen the anti-inflammatory activity of a series
      of PPH dendrimers bearing between 2 and 16 ABP end groups in a mouse model of
      arthritis and confront the biological results with atomistic simulations of the
      dendrimers. We show that only the PPH dendrimers capped with 10 and 12 ABP end
      groups can control the flare of the inflammatory disease. All-atom accelerated
      molecular dynamics simulations show that dendrimers with a low number of ABP end
      groups are directional but highly flexible/dynamic and have thereby limited
      efficiency in establishing multivalent interactions. The largest dendrimer
      appears as nondirectional, having 16 ABP end groups forming patches all over the
      dendrimer surface. Conversely, intermediate dendrimers having 10 or 12 ABP end
      groups reach the best compromise between the number of surface groups and their
      stable directional gathering, a real maximization of multivalency.

PMID- 29443508
TI  - Development of an Infection-Responsive Fluorescent Sensor for the Early Detection
      of Urinary Catheter Blockage.
AB  - Formation of crystalline biofilms following infection by Proteus mirabilis can
      lead to encrustation and blockage of long-term indwelling catheters, with serious
      clinical consequences. We describe a simple sensor, placed within the catheter
      drainage bag, to alert of impending blockage via a urinary color change. The pH
      responsive sensor is a dual-layered polymeric "lozenge", able to release the self
      quenching dye 5(6)-carboxyfluorescein in response to the alkaline urine generated
      by the expression of bacterial urease. Sensor performance was evaluated within a
      laboratory model of the catheterized urinary tract, infected with both urease
      positive and negative bacterial strains under conditions of established
      infection, achieving an average "early warning" of catheter blockage of 14.5 h.
      Signaling only occurred following infection with urease positive bacteria.
      Translation of these sensors into a clinical environment would allow appropriate
      intervention before the occurrence of catheter blockage, a problem for which
      there is currently no effective control method.

PMID- 29443510
TI  - De Novo Glycan Sequencing by Electronic Excitation Dissociation and Fixed-Charge
      Derivatization.
AB  - Detailed glycan structural characterization is frequently achieved by
      collisionally activated dissociation (CAD) based sequential tandem mass
      spectrometry (MS n) analysis of permethylated glycans. However, it is challenging
      to implement MS n ( n > 2) during online glycan separation, and this has limited
      its application to analysis of complex glycan mixtures from biological samples.
      Further, permethylation can reduce liquid chromatographic (LC) resolution of
      isomeric glycans. Here, we studied the electronic excitation dissociation (EED)
      fragmentation behavior of native glycans with a reducing-end fixed charge tag and
      identified key spectral features that are useful for topology and linkage
      determination. We also developed a de novo glycan sequencing software that showed
      remarkable accuracy in glycan topology elucidation based on the EED spectra of
      fixed charge-derivatized glycans. The ability to obtain glycan structural details
      at the MS2 level, without permethylation, via a combination of fixed charge
      derivatization, EED, and de novo spectral interpretation, makes the present
      approach a promising tool for comprehensive and rapid characterization of glycan
      mixtures.

PMID- 29443509
TI  - pH-Responsive Microencapsulation Systems for the Oral Delivery of Polyanhydride
      Nanoparticles.
AB  - Multicompartmental polymer carriers, referred to as Polyanhydride-Releasing Oral
      MicroParticle Technology (PROMPT), were formed by a pH-triggered antisolvent
      precipitation technique. Polyanhydride nanoparticles were encapsulated into
      anionic pH-responsive microparticle gels, allowing for nanoparticle encapsulation
      in acidic conditions and subsequent release in neutral pH conditions. The effects
      of varying the nanoparticle composition and feed ratio on the encapsulation
      efficiency were evaluated. Nanoparticle encapsulation was confirmed by confocal
      microscopy and infrared spectroscopy. pH-triggered protein delivery from PROMPT
      was explored using ovalbumin (ova) as a model drug. PROMPT microgels released ova
      in a pH-controlled manner. Increasing the feed ratio of nanoparticles into the
      microgels increased the total amount of ova delivered, as well as decreased the
      observed burst release. The cytocompatibility of the polymer materials were
      assessed using cells representative of the GI tract. Overall, these results
      suggest that pH-dependent microencapsulation is a viable platform to achieve
      targeted intestinal delivery of polyanhydride nanoparticles and their payload(s).

PMID- 29443511
TI  - LiNa4B15O25: Featuring Unprecedented B15O30 Fundamental Building Block and Deep
      UV Cutoff Edge.
AB  - In the Li2O-Na2O-B2O3 system, LiNa4B15O25 has been successfully synthesized,
      which crystallizes in monoclinic space group C2 /c (No. 15), a = 14.153(3) A, b =
      12.122(2) A, c = 12.719(2) A, beta = 105.237(13) degrees , and Z = 4. The
      isolated LiO5 polyhedra and the Na4O18 tetramers are located in the void space of
      the 3D infinity[B15O25] network of LiNa4B15O25. The symmetry of B15O30 is a new
      fundamental building block, which has never been reported before. Moreover, the
      whole framework can be defined as a new topology based on the TOPOS database.
      Interestingly, for the crystal structure LiB3O5, as 4/5 Li+ ions are substituted
      by the Na+ ions, a new compound LiNa4B15O25 has been successfully prepared. The
      structural comparison between the structures of LiB3O5 and LiNa4B15O25 and the
      changes caused by the cation substitution are discussed in this paper.

PMID- 29443512
TI  - Diels-Alder Click-Cross-Linked Hydrogels with Increased Reactivity Enable 3D Cell
      Encapsulation.
AB  - Engineered hydrogels have been extensively used to direct cell function in 3D
      cell culture models, which are more representative of the native cellular
      microenvironment than conventional 2D cell culture. Previously, hyaluronan-furan
      and bis-maleimide polyethylene glycol hydrogels were synthesized via Diels-Alder
      chemistry at acidic pH, which did not allow encapsulation of viable cells. In
      order to enable gelation at physiological pH, the reaction kinetics were
      accelerated by replacing the hyaluronan-furan with the more electron-rich
      hyaluronan-methylfuran. These new click-cross-linked hydrogels gel faster and at
      physiological pH, enabling encapsulation of viable cells, as demonstrated with 3D
      culture of 5 different cancer cell lines. The methylfuran accelerates Diels-Alder
      cycloaddition yet also increases the retro Diels-Alder reaction. Using
      computational analysis, we gain insight into the mechanism of the increased Diels
      Alder reactivity and uncover that transition state geometry and an unexpected
      hydrogen-bonding interaction are important contributors to the observed rate
      enhancement. This cross-linking strategy serves as a platform for bioconjugation
      and hydrogel synthesis for use in 3D cell culture and tissue engineering.

PMID- 29443513
TI  - Mass-Remainder Analysis (MARA): a New Data Mining Tool for Copolymer
      Characterization.
AB  - A new data mining method is proposed for the determination of the copolymer
      composition from moderate/low resolution complex mass spectra. The Mass-remainder
      analysis (MARA) does not require a "Kendrick-like" transformation to a new mass
      scale, it is simply based on the calculation of the remainder after dividing by
      the exact mass of one of the repeat units of the copolymer (e.g., B of an A/B
      copolymer). Plotting the remainder of this division (MR) versus m/ z the
      homologous series differing only by a number of base units (e.g., B unit) can be
      visualized. The number of A units ( nA) and subsequently nB is assigned to the m/
      z peaks using the bijective nA, MR mapping. Simultaneously, our algorithm removes
      the isotopes from the peak list. However, the intensities of the monoisotopes are
      increased to the value corresponding, approximately, to the total intensity of
      their isotope peaks. The correction of the mass spectral peak intensities enables
      the accurate calculation of the usual polymer and copolymer quantities: the
      molecular weight-average, the number-averaged molecular weight of A and B units,
      the composition drift, or the bivariate distribution, among others. Our Mass
      remainder analysis method was demonstrated by the analysis of various ethylene
      oxide/propylene oxide copolymers.

PMID- 29443514
TI  - Environmentally Persistent Free Radicals: Insights on a New Class of Pollutants.
AB  - Environmentally persistent free radicals, EPFRs, exist in significant
      concentration in atmospheric particulate matter (PM). EPFRs are primarily emitted
      from combustion and thermal processing of organic materials, in which the organic
      combustion byproducts interact with transition metal-containing particles to form
      a free radical-particle pollutant. While the existence of persistent free
      radicals in combustion has been known for over half-a-century, only recently that
      their presence in environmental matrices and health effects have started
      significant research, but still in its infancy. Most of the experimental studies
      conducted to understand the origin and nature of EPFRs have focused primarily on
      nanoparticles that are supported on a larger micrometer-sized particle that
      mimics incidental nanoparticles formed during combustion. Less is known on the
      extent by which EPFRs may form on engineered nanomaterials (ENMs) during
      combustion or thermal treatment. In this critical and timely review, we summarize
      important findings on EPFRs and discuss their potential to form on pristine ENMs
      as a new research direction. ENMs may form EPFRs that may differ in type and
      concentration compared to nanoparticles that are supported on larger particles.
      The lack of basic data and fundamental knowledge about the interaction of
      combustion byproducts with ENMs under high-temperature and oxidative conditions
      present an unknown environmental and health burden. Studying the extent of ENMs
      on catalyzing EPFRs is important to address the hazards of atmospheric PM fully
      from these emerging environmental contaminants.

PMID- 29443515
TI  - Tuning Inner-Ear Tip-Link Affinity Through Alternatively Spliced Variants of
      Protocadherin-15.
AB  - Human hearing relies upon the tip-to-tip interaction of two nonclassical
      cadherins, protocadherin-15 (PCDH15) and cadherin-23 (CDH23). Together, these
      proteins form a filament called the tip link that connects neighboring
      stereocilia of mechanosensitive hair cells. As sound waves enter the cochlea, the
      stereocilia deflect and tension is applied to the tip link, opening nearby
      transduction channels. Disruption of the tip link by loud sound or calcium
      chelators eliminates transduction currents and illustrates that tip-link
      integrity is critical for mechanosensing. Tip-link remodeling after disruption is
      a dynamic process, which can lead to the formation of atypical complexes that
      incorporate alternatively spliced variants of PCDH15. These variants are
      categorized into six groups (N1-N6) based upon differences in the first two
      extracellular cadherin (EC) repeats. Here, we characterized the two N-terminal EC
      repeats of all PCDH15 variants (pcdh15(N1) to pcdh15(N6)) and combined these
      variants to test complex formation. We solved the crystal structure of a new
      complex composed of CDH23 EC1-2 (cdh23) and pcdh15(N2) at 2.3 A resolution and
      compared it to the canonical cdh23-pcdh15(N1) complex. While there were subtle
      structural differences, the binding affinity between cdh23 and pcdh15(N2) is ~6
      times weaker than cdh23 and pcdh15(N1) as determined by surface plasmon resonance
      analysis. Steered molecular dynamics simulations predict that the unbinding force
      of the cdh23-pcdh15(N2) complex can be lower than the canonical tip link. Our
      results demonstrate that alternative heterophilic tip-link structures form stable
      protein-protein interactions in vitro and suggest that homophilic PCDH15-PCDH15
      tip links form through the interaction of additional EC repeats.

PMID- 29443516
TI  - A Versatile and Robust Approach to Stimuli-Responsive Protein Multilayers with
      Biologically Enabled Unique Functions.
AB  - Protein-based materials call for innovative processing techniques to integrate
      their unique biologically enabled functions with other materials of complementary
      features. Herein, we report the covalent protein layer-by-layer assembly via
      orthogonal "Tag-Catcher" reactions as a facile and robust approach to make
      entirely protein-based multilayers on a variety of substrates. Programmed
      assembly of native telechelic proteins not only endows the materials valuable
      stimuli-sensitive behaviors, but also unique properties unparalleled by any
      synthetic counterparts. As proof of concept, super uranyl-binding protein (SUP)
      is immobilized on silica gel by this method with tunable capacity and enhanced
      capability for uranyl sequestration. Not only is the capturing performance
      enhanced in the multilayer setup, it also confers resilience to recycling,
      allowing efficient harvest of uranyl with an average of ~90% and ~60% recovery
      rate in over 10 cycles from water and synthetic seawater, respectively. The
      approach is the first entirely protein-based multilayers covalently assembled by
      the layer-by-layer method. It provides a platform for immobilizing proteins with
      synergistic enhancement of function and resilience and expands the scope and
      capability of genetically encoded protein-based materials.

PMID- 29443517
TI  - Lewis Acid Assisted Nitrate Reduction with Biomimetic Molybdenum Oxotransferase
      Complex.
AB  - The reduction of nitrate (NO3-) to nitrite (NO2-) is of significant biological
      and environmental importance. While MoIV(O) and MoVI(O)2 complexes that mimic the
      active site structure of nitrate reducing enzymes are prevalent, few of these
      model complexes can reduce nitrate to nitrite through oxygen atom transfer (OAT)
      chemistry. We present a novel strategy to induce nitrate reduction chemistry of a
      previously known catalyst MoIV(O)(SN)2 (2), where SN = bis(4- tert-butylphenyl)-2
      pyridylmethanethiolate, that is otherwise incapable of achieving OAT with
      nitrate. Addition of nitrate with the Lewis acid Sc(OTf)3 (OTf =
      trifluoromethanesulfonate) to 2 results in an immediate and clean conversion of 2
      to MoVI(O)2(SN)2 (1). The Lewis acid additive further reacts with the OAT
      product, nitrite, to form N2O and O2. This work highlights the ability of Sc3+
      additives to expand the reactivity scope of an existing MoIV(O) complex together
      with which Sc3+ can convert nitrate to stable gaseous molecules.

PMID- 29443518
TI  - Highly Selective and Rapid Breath Isoprene Sensing Enabled by Activated Alumina
      Filter.
AB  - Isoprene is a versatile breath marker for noninvasive monitoring of high blood
      cholesterol levels as well as for influenza, end-stage renal disease, muscle
      activity, lung cancer, and liver disease with advanced fibrosis. Its selective
      detection in complex human breath by portable devices (e.g., metal-oxide gas
      sensors), however, is still challenging. Here, we present a new filter concept
      based on activated alumina powder enabling fast and highly selective detection of
      isoprene at the ppb level and high humidity. The filter contains high surface
      area adsorbents that retain hydrophilic compounds (e.g., ketones, alcohols,
      ammonia) representing major interferants in breath while hydrophobic isoprene is
      not affected. As a proof-of-concept, filters of commercial activated alumina
      powder are combined with highly sensitive but rather nonspecific, nanostructured
      Pt-doped SnO2 sensors. This results in fast (10 s) measurement of isoprene down
      to 5 ppb at 90% relative humidity with outstanding selectivity (>100) to breath
      relevant acetone, ammonia, ethanol, and methanol, superior to state-of-the-art
      isoprene sensors. Most importantly, when exposed continuously to simulated breath
      mixtures (four analytes) for 8 days, this filter-sensor system showed stable
      performance. It can be incorporated readily into a portable breath isoprene
      analyzer promising for simple-in-use monitoring of blood cholesterol or other
      patho/physiological conditions.

PMID- 29443519
TI  - Mercury Trithiolate Binding (HgS3) to a de Novo Designed Cyclic Decapeptide with
      Three Preoriented Cysteine Side Chains.
AB  - Mercury(II) is an unphysiological soft ion with high binding affinity for
      thiolate ligands. Its toxicity lies in the interactions with low molecular weight
      thiols including glutathione and cysteine-containing proteins that disrupt the
      thiol balance and alter vital functions. However, mercury can also be detoxified
      via interactions with Hg(II)-responsive regulatory proteins such as MerR, which
      coordinates Hg(II) with three cysteine residues in a trigonal planar fashion
      (HgS3 coordination). The model cyclodecapeptide P3C, c(GCTCSGCSRP) was designed
      to promote Hg(II) chelation in a HgS3 coordination environment through the
      parallel orientation of three cysteine side chains. The binding motif is derived
      from the dicysteine P2C cyclodecapeptide validated previously as a model for d10
      metal transporters containing the binding sequence CxxC. The formation of the
      mononuclear HgP3C complex with a HgS3 coordination is demonstrated using
      electrospray ionization mass spectrometry, UV absorption, and 199Hg NMR. Hg LIII
      edge extended X-ray absorption fine structure (EXAFS) spectroscopy indicates that
      the Hg(II) coordination environment is T-shaped with two short Hg-S distances at
      2.45 A and one longer distance at 2.60 A. The solution structure of the HgP3C
      complex was refined based on 1H-1H NMR constraints and EXAFS results. The cyclic
      peptide scaffold has a rectangular shape with the three binding cysteine side
      chains pointing toward Hg(II). The HgP3CH complex has a p Ka of 4.3, indicating
      that the HgS3 coordination mode is stable over a large range of pH. This low p Ka
      value suggests that the preorientation of the three cysteine groups is
      particularly well-achieved for Hg(II) trithiolate coordination in P3C.

PMID- 29443520
TI  - Cosolvent Effects on Polymer Hydration Drive Hydrophobic Collapse.
AB  - Water-mediated hydrophobic interactions play an important role in self-assembly
      processes, aqueous polymer solubility, and protein folding, to name a few.
      Cosolvents affect these interactions; however, the implications for hydrophobic
      polymer collapse and protein folding equilibria are not well-understood. This
      study examines cosolvent effects on the hydrophobic collapse equilibrium of a
      generic 32-mer hydrophobic polymer in urea, trimethylamine- N-oxide (TMAO), and
      acetone aqueous solutions using molecular dynamics simulations. Our results
      unveil a remarkable cosolvent-concentration-dependent behavior. Urea, TMAO, and
      acetone all shift the equilibrium toward collapsed structures below 2 M cosolvent
      concentration and, in turn, to unfolded structures at higher cosolvent
      concentrations, irrespective of the differences in cosolvent chemistry and the
      nature of cosolvent-water interactions. We find that weakly attractive polymer
      water van der Waals interactions oppose polymer collapse in pure water,
      corroborating related observations reviewed by Ben-Amotz ( Annu. Rev. Phys. Chem.
      2016, 67, 617-638). The cosolvents studied in the present work adsorb at the
      polymer/water interface and expel water molecules into the bulk, thereby
      effectively removing the dehydration energy penalty that opposes polymer collapse
      in pure water. At low cosolvent concentrations, this leads to cosolvent-induced
      stabilization of collapsed polymer structures. Only at sufficiently high
      cosolvent concentrations, polymer-cosolvent interactions favor polymer unfolding.

PMID- 29443521
TI  - The Structure and Cl-O Dissociation Energy of the ClOO Radical: Finally, the
      Right Answers for the Right Reason.
AB  - The chlorine peroxy radical (ClOO) has historically been a highly problematic
      system for theoretical studies. In particular, the erratic ab initio predictions
      of the Cl-O bond length reported in the literature thus far exhibit unacceptable
      errors with respect to the experimental structure. In light of the widespread
      disagreement observed, we present a careful and systematic investigation of the
      ClOO geometry toward the basis set and correlation limits of single reference ab
      initio theory, employing the cc-pVXZ (X = D, T, Q, 5, 6) basis sets extrapolated
      to the complete basis set limit and coupled cluster theory through single,
      double, triple, and perturbative quadruple excitations [CCSDT(Q)]. We demonstrate
      a considerable sensitivity of the Cl-O bond length to both electron correlation
      and basis set size. The CCSDT(Q)/CBS structure is found to be re(ClO) = 2.082,
      re(OO) = 1.208, and thetae(ClOO) = 115.4 degrees , in remarkable agreement with
      Endo's semi-experimentally determined values re(ClO) = 2.084(1), re(OO) =
      1.206(2), and thetae(ClOO) = 115.4(1) degrees . Moreover, we compute a Cl-O bond
      dissociation energy of 4.77 kcal mol-1, which is likewise in excellent agreement
      with the most recent experimental value of 4.69 +/- 0.10 kcal mol-1.

PMID- 29443522
TI  - An in Situ Embedded Square-Planar CuII/NiIIN4 Metalloligand in Coordination
      Polymers for Visible-Light Photocatalysis.
AB  - Three coordination polymers (CPs) with square-planar CuII/NiIIN4 subunits were
      formed in one step by subcomponent self-assembly, giving rise to an unprecedented
      linking variety of in situ embedded metalloligands and CuI clusters. All CPs
      exhibit unusual visible-light adsorption. Enhanced photocatalytic activity and
      high selectivity were observed in the oxidation of benzene under visible-light
      irradiation.

PMID- 29443523
TI  - Simple Approach for the Rapid Detection of Alternariol in Pear Fruit by Surface
      Enhanced Raman Scattering with Pyridine-Modified Silver Nanoparticles.
AB  - A simple method based on surface-enhanced Raman scattering (SERS) was developed
      for the rapid determination of alternariol (AOH) in pear fruits using an easily
      prepared silver-nanoparticle (AgNP) substrate. The AgNP substrate was modified by
      pyridine to circumvent the weak affinity of the AOH molecules to the silver
      surface and to improve the sensitivity of detection. Quantitative analysis was
      performed in AOH solutions at concentrations ranging from 3.16 to 316.0 MUg/L,
      and the limit of detection was 1.30 MUg/L. The novel method was also applied to
      the detection of AOH residues in pear fruits purchased from the market and in
      pear fruits that were artificially inoculated with Alternaria alternata. AOH was
      not found in any of the fresh fruit, whereas it resided in the rotten and
      inoculated fruits. Finally, the SERS method was cross validated against HPLC. It
      was revealed that the SERS method has great potential utility in the rapid
      detection of AOH in pear fruits and other agricultural products.

PMID- 29443524
TI  - Encapsulation of Ionic Liquids with an Aprotic Heterocyclic Anion (AHA-IL) for
      CO2 Capture: Preserving the Favorable Thermodynamics and Enhancing the Kinetics
      of Absorption.
AB  - The performance of an ionic liquid with an aprotic heterocyclic anion (AHA-IL),
      trihexyl(tetradecyl)phosphonium 2-cyanopyrrolide ([P66614][2-CNPyr]), for CO2
      capture has been evaluated considering both the thermodynamics and the kinetics
      of the phenomena. Absorption gravimetric measurements of the gas-liquid
      equilibrium isotherms of CO2-AHA-IL systems were carried out from 298 to 333 K
      and at pressures up to 15 bar, analyzing the role of both chemical and physical
      absorption phenomena in the overall CO2 solubility in the AHA-IL, as has been
      done previously. In addition, the kinetics of the CO2 chemical absorption process
      was evaluated by in situ Fourier transform infrared spectroscopy-attenuated total
      reflection, following the characteristic vibrational signals of the reactants and
      products over the reaction time. A chemical absorption model was used to describe
      the time-dependent concentration of species involved in the reactive absorption,
      obtaining kinetic parameters (such as chemical reaction kinetic constants and
      diffusion coefficients) as a function of temperatures and pressures. As expected,
      the results demonstrate that the CO2 absorption rate is mass-transfer-controlled
      because of the relatively high viscosity of AHA-IL. The AHA-IL was encapsulated
      in a porous carbon sphere (Encapsulated Ionic Liquid, ENIL) to improve the
      kinetic performance of the AHA-IL for CO2 capture. The newly synthesized AHA-ENIL
      material was evaluated as a CO2 sorbent with gravimetric absorption measurements.
      AHA-ENIL systems preserve the good CO2 absorption capacity of the AHA-IL but
      drastically enhance the CO2 absorption rate because of the increased gas-liquid
      surface contact area achieved by solvent encapsulation.

PMID- 29443525
TI  - New Knowledge-Based Scoring Function with Inclusion of Backbone Conformational
      Entropies from Protein Structures.
AB  - Accurate prediction of a protein's structure requires a reliable free energy
      function that consists of both enthalpic and entropic contributions. Although
      considerable progresses have been made in the calculation of potential energies
      in protein structure prediction, the computation for entropies of protein has
      lagged far behind, due to the challenge that estimation of entropies often
      requires expensive conformational sampling. In this study, we have used a
      knowledge-based approach to estimate the backbone conformational entropies from
      experimentally determined structures. Instead of conducting computationally
      expensive MD/MC simulations, we obtained the entropies of protein structures
      based on the normalized probability distributions of back dihedral angles
      observed in the native structures. Our new knowledge-based scoring function with
      inclusion of the backbone entropies, which is referred to as ITScoreDA or ITDA,
      was extensively evaluated on 16 commonly used decoy sets and compared with 50
      other published scoring functions. It was shown that ITDA is significantly
      superior to the other tested scoring functions in selecting native structures
      from decoys. The present study suggests the role of backbone conformational
      entropies in protein structures and provides a way for fast estimation of the
      entropic effect.

PMID- 29443526
TI  - Comment on mRNA-Sequencing Analysis Reveals Transcriptional Changes in Root of
      Maize Seedlings Treated with Two Increasing Concentrations of a New Biostimulant.
AB  - Overpopulation is already a reality, and the need for alternative technologies to
      meet a continuously increasing food demand has been much discussed around the
      world. In addition, soil decreasing fertility and desertification are obstacles
      that we will need to be overcome to increase crop productivity with a much
      reduced dependence upon inorganic fertilizers. In this context, protein
      hydrolysates has emerged as an important strategy to reduce the use of inorganic
      fertilizers, whose applications as biostimulants for plant growth have shown very
      promising results.

PMID- 29443527
TI  - Positron Scattering from Methyl Halides.
AB  - The well-known spherical complex optical potential (SCOP) and complex scattering
      potential-ionization contribution (CSP-ic) methods with appropriate modifications
      are applied to the CH3X (X = F, Cl, Br, and I) molecules to compute positron
      scattering cross sections, which rather is the first theoretical attempt to
      report the same. Besides, various inelastic cross sections are also predicted for
      the first time in this Article. We have utilized the multiscattering spherical
      complex optical potential (MSCOP) approach to derive these cross sections. In
      general, a reasonable accordance has been found between the present total cross
      sections and the experimental measurements. Apart from the inconsistency between
      the present theoretical and previous experimental cross sections in the low
      energy region, the present theory is found to produce consistent and reliable
      results at all other energies.

PMID- 29443528
TI  - Lambda-Doublet Propensities for Reactions on Competing A' and A" Potential Energy
      Surfaces: O(3 P) + N2 and O(3 P) + HCl.
AB  - This work presents scattering calculations for the O(3 P) + N2(1Sigma) -> NO(2Pi)
      + N(4S) and for the O(3 P) + HCl(1Sigma) -> OH(2Pi) + Cl(2P) reactions with a
      focus on the prediction of the Lambda-doublet populations in which NO and OH are
      produced. Both reactions can take place on two competing potential energy
      surfaces of symmetries 3 A' and 3 A" that correlate reagents with products but
      with very distinct topographies. As a result, they exhibit very different
      dynamical behaviors and total reactivity. Using a method that relates the
      reaction yield on the two competing surfaces to the Lambda-doublet populations
      through the explicit consideration of the stereodynamics of the reaction, we
      predict that the population of NO and OH on the two Lambda-doublet sates is
      surprisingly similar for both systems. These results contradict the model that
      assumes that collisions on the 3 A' and 3 A" would give rise to products in the
      Pi( A') and Pi( A") states, respectively.

PMID- 29443529
TI  - Amido Ca and Yb(II) Complexes Coordinated by Amidine-Amidopyridinate Ligands for
      Catalytic Intermolecular Olefin Hydrophosphination.
AB  - A series of amido Ca and Yb(II) complexes LM[N(SiMe3)2](THF) (1Yb, 1-4Ca)
      coordinated by amidine-amidopyridinate ligands L1-4 were synthesized via a
      transamination reaction between proligands L1-4H and bisamido complexes
      M[N(SiMe3)2]2(THF)2 (M = Yb, Ca). The reactions of Yb[N(SiMe3)2]2(THF)2 with
      proligands L2H-L4H containing CF3 and C6H4F fragments do not allow for preparing
      the target Yb(II) complexes, while the Ca analogues were synthesized in good
      yields. Complexes 1Yb and 1-4Ca were evaluated as precatalysts for
      hydrophosphination of styrene, p-substituted styrenes, alpha-Me-styrene, and 2,3
      dimethylbutadiene with various primary and secondary phosphines (PhPH2, 2,4,6
      Me3C6H2PH2, 2-C5NH4PH2, Ph2PH, Cy2PH). Complexes 1Yb, 1-4Ca performed high
      catalytic activities in styrene hydrophosphination with PhPH2 and Ph2PH and
      demonstrated high regioselectivity affording exclusively the anti-Markovnikov
      addition products. For primary PhPH2 the reactions (1:1 molar ratio of
      substrates) catalyzed by 1Yb, 1Ca, and 2Ca proved to be highly chemoselective
      affording the secondary phosphine Ph(PhCH2CH2)PH; however, complexes 3Ca and 4Ca
      led to the formation of both secondary and tertiary phosphines in 80:20 and 86:14
      ratios. Styrene hydrophosphinations with 2,4,6-Me3C6H2PH2 and 2-pyridylphosphine
      for all complexes 1Yb and 1-4Ca proceeded much more slowly compared to PhPH2.
      Addition of 2-C5NH4PH2 to styrene catalyzed by complex 1Yb turned out to be non
      regioselective and led to the formation of a mixture of Markovnikov and anti
      Markovnikov addition products, while all Ca complexes enabled regioselective anti
      Markovnikov addition. Complexes 1Ca and 1Yb containing catalytic centers
      featuring similar ionic radii performed different catalytic activity: the
      ytterbium analogue proved to be a more active catalyst for intermolecular
      hydrophosphination of styrene with Cy2PH, 2-C5NH4PH2, and PhPH2, but less active
      with sterically demanding 2,4,6-Me3C6H2PH2. Styrenes containing in p-position
      electron-donating groups (Me, tBu, OMe) performed with noticeably lower rates in
      the reactions with PhPH2 compared to styrene. Complexes 1Yb, 1Ca, 2Ca, 3Ca, and
      4Ca enabled addition of PhPH2 toward the double C?C bond of alpha-Me-styrene, and
      the reaction rate for this substrate is noticeably lower; however quantitative
      conversions were reached in ~40 h. Complexes 1Ca and 2Ca promoted 1,2-addition of
      PhPH2 to 2,3-dimethyl butadiene with excellent regio- and chemoselectivity to
      afford linear secondary phosphines. Hydrophosphination of inert 1-nonene with
      Ph2PH with 40% conversion becomes possible due to the application of complex 2Ca
      (40 h, 70  degrees C). The rate law for the hydrophosphination of styrene with
      Ph2PH catalyzed by 1Ca was found to agree with the idealized equation: v =
      k[styrene]1[1Ca]1.

PMID- 29443530
TI  - Competitive Multiple-Mechanism-Driven Electrochemiluminescent Detection of 8
      Hydroxy-2'-deoxyguanosine.
AB  - Natural selection over billions of years has developed highly effective in vivo
      signal transduction that is often governed by a series of competitive multiple
      mechanisms. Several artificial signal transduction pathways have inspired
      numerous biosensing systems, but most of these are driven by a single mechanism.
      Herein we describe a multiple-mechanism-driven electrochemiluminescent (ECL)
      biosensor that utilizes competitive catalytic and steric hindrance effects by
      assembling hemin/G-quadruplex on carbon nitride nanosheets. Taking the detection
      of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as example, the dynamic ranges of the
      detectable concentrations from the different mechanisms were integrated into a
      single sensor interface. Moreover, the detection sensitivity was more precisely
      controlled by the competition between the two mechanisms and inherently boosted
      compared with that of single-mechanism-driven detection. Going beyond the
      conventional single-mechanism-driven biosensing, the elaborate biomimetic
      coupling of multiple mechanisms in a single interface may open a new approach for
      future multiplexed biosensing.

PMID- 29443531
TI  - Application of Copper-Chitosan Nanoparticles Stimulate Growth and Induce
      Resistance in Finger Millet (Eleusine coracana Gaertn.) Plants against Blast
      Disease.
AB  - Copper-chitosan nanoparticle (CuChNp) was synthesized and used to study its
      effect on finger millet plant as a model plant system. Our objective was to
      explore the efficacy of CuChNp application to control blast disease of finger
      millet. CuChNp was applied to finger millet either as a foliar spray or as a
      combined application (involving seed coat and foliar spray). Both the application
      methods enhanced growth profile of finger millet plants and increased yield. The
      increased yield was nearly 89% in combined application method. Treated finger
      millet plants challenged with Pyricularia grisea showed suppression of blast
      disease development when compared to control. Nearly 75% protection was observed
      in the combined application of CuChNp to finger millet plants. In CuChNp treated
      finger millet plants, a significant increase in defense enzymes was observed,
      which was detected both qualitatively and quantitatively. The suppression of
      blast disease correlates well with increased defense enzymes in CuChNp treated
      finger millet plants.

PMID- 29443532
TI  - Aggregate Formation of Surface-Modified Nanoparticles in Solvents and Polymer
      Nanocomposites.
AB  - A new method based on the combination of small-angle scattering, reverse Monte
      Carlo simulations, and an aggregate recognition algorithm is proposed to
      characterize the structure of nanoparticle suspensions in solvents and polymer
      nanocomposites, allowing detailed studies of the impact of different nanoparticle
      surface modifications. Experimental small-angle scattering is reproduced using
      simulated annealing of configurations of polydisperse particles in a simulation
      box compatible with the lowest experimental q-vector. Then, properties of
      interest like aggregation states are extracted from these configurations and
      averaged. This approach has been applied to silane surface-modified silica
      nanoparticles with different grafting groups, in solvents and after casting into
      polymer matrices. It is shown that the chemistry of the silane function, in
      particular mono- or trifunctionality possibly related to patch formation, affects
      the dispersion state in a given medium, in spite of an unchanged alkyl-chain
      length. Our approach may be applied to study any dispersion or aggregation state
      of nanoparticles. Concerning nanocomposites, the method has potential impact on
      the design of new formulations allowing controlled tuning of nanoparticle
      dispersion.

PMID- 29443533
TI  - The Effects of a Yoga Exercise and Nutritional Guidance Program on Pregnancy
      Outcomes Among Healthy Pregnant Japanese Women: A Study Protocol for a Randomized
      Controlled Trial.
AB  - OBJECTIVES: This report provides an experimental protocol for a study designed to
      verify the effects of yoga exercise and a nutritional guidance program during
      pregnancy on several key pregnancy and birth outcomes among Japanese women.
      DESIGN: This is a study protocol of a randomized controlled trial.
      SETTING/LOCATION: This intervention will be carried out in a university hospital
      in Tokyo. SUBJECTS: Healthy primiparous women will be recruited at 18-23
      gestational weeks in the hospital. A total of 400 participants will be randomly
      assigned to one of four groups in this trial, with 100 participants in each group
      group with yoga exercise, with nutritional guidance, with both yoga and
      nutritional guidance, and with standard care alone, as the control group. Yoga
      exercise consists of yoga classes held at the hospital 3 or 5 days a month,
      duration 60 min, and home practice using a digital video disk, duration 30 or 60
      min per session. We recommend participants do yoga at least 3 days a week for a
      total of 60 min per day. Nutritional guidance is based on individual dietary
      intake assessed using a brief-type diet history questionnaire. RESULTS: The
      primary outcome is rate of pregnant women with adequate gestational weight gain.
      Secondary outcomes include physiologic and psychologic status assessed via
      biomarkers and health-related scales, dietary nutrition intake, and birth
      outcomes. CONCLUSIONS: This study shows the effects of a yoga exercise and
      nutritional intervention. If the intervention is found to be effective, our
      results will be useful for healthcare providers and pregnant women.

PMID- 29443534
TI  - Breastfeeding Is Primary.

PMID- 29443535
TI  - Literature Search and Review.

PMID- 29443536
TI  - Minding the Mind-Body Literature: Aging and Cognitive Decline.

PMID- 29443537
TI  - A Randomized Clinical Trial to Evaluate Attached Hamstring Anterior Cruciate
      Ligament Graft Maturity With Magnetic Resonance Imaging.
AB  - BACKGROUND: The hamstring tendons are commonly harvested for anterior cruciate
      ligament (ACL) reconstruction with detachment of the tibial insertion. Retaining
      the insertion may help to preserve vascularity and viability of the graft and
      bypass the stages of avascular necrosis and revascularization, which might be
      beneficial to graft maturity. PURPOSE: To investigate and compare graft maturity
      by magnetic resonance imaging (MRI) after ACL reconstruction with preservation or
      detachment of hamstring tendon tibial insertion at up to 2 years. STUDY DESIGN:
      Randomized controlled trial; Level of evidence, 2. METHODS: Forty-five patients
      (age range, 18-45 years) undergoing isolated ACL reconstruction with hamstring
      tendon were enrolled and randomized to 2 groups. The tibial insertion of the
      hamstring tendon was preserved in the study group (n = 21) and detached in the
      control group (n = 24). Patients had follow-up at 3, 6, 12, and 24 months, which
      consisted of the following: (1) clinical examination and (2) MRI evaluation of
      graft signal intensity based on signal/noise quotient (SNQ) values. Finally, 18
      patients in the study group and 19 in the control group received full follow-up
      evaluation (ie, at all 4 time points). RESULTS: All knees acquired full range of
      motion at 24 months without significant laxity. At each time point, the KT-1000
      arthrometer revealed no significant difference between groups; the clinical
      scores significantly improved in both groups, although the difference between
      groups was not significant. In the control group, the SNQ value increased from 3
      months, peaked at 6 months, and then decreased (3 months, 21.4 +/- 12.7; 6
      months, 25.6 +/- 12; 12 months, 18.3 +/- 7.7; 24 months, 15.3 +/- 6.3). However,
      the insertion-preserved graft in the study group maintained relatively lower and
      unchanged signal intensity throughout all time points (3 months, 15.0 +/- 11.2; 6
      months, 14.9 +/- 6.3; 12 months, 12.6 +/- 7.0; 24 months, 14.6 +/- 7.0). Between
      groups, there was no significant difference at 3 or 24 months ( P = .11 and .75,
      respectively), while the SNQ values were significantly lower in the study group
      versus the control group at 6 and 12 months ( P = .002 and .02, respectively).
      CONCLUSION: The insertion-detached hamstring tendon grafts underwent a
      significantly increasing change in signal intensity during the first 2 years
      after ACL reconstruction, while the insertion-preserved grafts kept a relatively
      lower and unchanged signal intensity. The difference was most significant at 6
      and 12 months postoperatively.

PMID- 29443538
TI  - Arthroscopic Surgery or Physical Therapy for Patients With Femoroacetabular
      Impingement Syndrome: A Randomized Controlled Trial With 2-Year Follow-up.
AB  - BACKGROUND: Arthroscopic hip surgery has risen 18-fold in the past decade;
      however, there is a dearth of clinical trials comparing surgery with nonoperative
      management. PURPOSE: To determine the comparative effectiveness of surgery and
      physical therapy for femoroacetabular impingement syndrome. STUDY DESIGN:
      Randomized controlled trial; Level of evidence, 1. METHODS: Patients were
      recruited from a large military hospital after referral to the orthopaedic
      surgery clinic and were eligible for surgery. Of 104 eligible patients, 80
      elected to participate, and the majority were active-duty service members
      (91.3%). No patients withdrew because of adverse events. The authors randomly
      selected patients to undergo either arthroscopic hip surgery (surgery group) or
      physical therapy (rehabilitation group). Patients in the rehabilitation group
      began a 12-session supervised clinic program within 3 weeks, and patients in the
      surgery group were scheduled for the next available surgery at a mean of 4 months
      after enrollment. Patient-reported outcomes of pain, disability, and perception
      of improvement over a 2-year period were collected. The primary outcome was the
      Hip Outcome Score (HOS; range, 0-100 [lower scores indicating greater
      disability]; 2 subscales: activities of daily living and sport). Secondary
      measures included the International Hip Outcome Tool (iHOT-33), Global Rating of
      Change (GRC), and return to work at 2 years. The primary analysis was on patients
      within their original randomization group. RESULTS: Statistically significant
      improvements were seen in both groups on the HOS and iHOT-33, but the mean
      difference was not significant between the groups at 2 years (HOS activities of
      daily living, 3.8 [95% CI, -6.0 to 13.6]; HOS sport, 1.8 [95% CI, -11.2 to 14.7];
      iHOT-33, 6.3 [95% CI, -6.1 to 18.7]). The median GRC across all patients was that
      they "felt about the same" (GRC = 0). Two patients assigned to the surgery group
      did not undergo surgery, and 28 patients in the rehabilitation group ended up
      undergoing surgery. A sensitivity analysis of "actual surgery" to "no surgery"
      did not change the outcome. Twenty (33.3%) patients who underwent surgery and 4
      (33.3%) who did not undergo surgery were medically separated from military
      service at 2 years. CONCLUSION: There was no significant difference between the
      groups at 2 years. Most patients perceived little to no change in status at 2
      years, and one-third of military patients were not medically fit for duty at 2
      years. Limitations include a single hospital, a single surgeon, and a high rate
      of crossover. Registration: NCT01993615 ( ClinicalTrials.gov identifier).

PMID- 29443539
TI  - Intermittent Exposure to Cigarette Smoke Increases Lung Tumors and the Severity
      of Emphysema More than Continuous Exposure.
AB  - Lung cancer and chronic obstructive pulmonary disease are leading causes of
      morbidity and mortality worldwide, and cigarette smoking is a main risk factor
      for both. The presence of emphysema, an irreversible lung disease, further raises
      the risk of lung cancer in patients with chronic obstructive pulmonary disease.
      The mechanisms involved in smoke-induced tumorigenesis and emphysema are not
      fully understood, attributable to a lack of appropriate animal models. Here, we
      optimized a model of cigarette smoke (CS)-induced lung cancer and emphysema in
      A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a potent
      carcinogen. We investigated whether variations in CS exposure patterns with the
      same total amount and duration of exposure affect tumorigenesis and/or
      development of emphysema. Continuous CS exposure for 3 months significantly
      suppressed 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced development of
      adenomas and adenocarcinomas; however, emphysema independently developed during
      this period. Surprisingly, intermittent CS exposure increased the severity of
      emphysema and resulted in a higher incidence of adenocarcinomas. Furthermore,
      intermittent CS exposure elicited a marked increase in M2-polarized macrophages
      within and near the developed tumors. By employing a CS exposure protocol with
      repeated cycles of cessation and relapse, we provide evidence that intermittent
      CS exposure enhances tumorigenesis and emphysema progression more than that of
      continuous CS exposure.

PMID- 29443540
TI  - Targeted Elimination of Peroxisomes During Viral Infection: Lessons from HIV and
      Other Viruses.
AB  - Peroxisomes are membrane-bound organelles that are best known for their roles in
      lipid metabolism. Mounting evidence indicates that they are also important nodes
      for antiviral signaling. While research over the past few decades has revealed
      effective viral strategies to block antiviral signalling pathways from the plasma
      membrane, mitochondria and/or the nucleus, until recently, very little was known
      about how viruses interfere with peroxisome-based antiviral signaling. In this
      essay, we review how viruses use a variety of strategies to interfere with
      peroxisome biogenesis, a phenomenon that has implications for evasion of the host
      immune system as well as pathogenesis.

PMID- 29443541
TI  - A Method for Choosing the Best Samples for Mars Sample Return.
AB  - Success of a future Mars Sample Return mission will depend on the correct choice
      of samples. Pyrolysis-FTIR can be employed as a triage instrument for Mars Sample
      Return. The technique can thermally dissociate minerals and organic matter for
      detection. Identification of certain mineral types can determine the habitability
      of the depositional environment, past or present, while detection of organic
      matter may suggest past or present habitation. In Mars' history, the Theiikian
      era represents an attractive target for life search missions and the acquisition
      of samples. The acidic and increasingly dry Theiikian may have been habitable and
      followed a lengthy neutral and wet period in Mars' history during which life
      could have originated and proliferated to achieve relatively abundant levels of
      biomass with a wide distribution. Moreover, the sulfate minerals produced in the
      Theiikian are also known to be good preservers of organic matter. We have used
      pyrolysis-FTIR and samples from a Mars analog ferrous acid stream with a thriving
      ecosystem to test the triage concept. Pyrolysis-FTIR identified those samples
      with the greatest probability of habitability and habitation. A three-tier
      scoring system was developed based on the detection of (i) organic signals, (ii)
      carbon dioxide and water, and (iii) sulfur dioxide. The presence of each
      component was given a score of A, B, or C depending on whether the substance had
      been detected, tentatively detected, or not detected, respectively. Single-step
      (for greatest possible sensitivity) or multistep (for more diagnostic data)
      pyrolysis-FTIR methods informed the assignments. The system allowed the highest
      priority samples to be categorized as AAA (or A*AA if the organic signal was
      complex), while the lowest-priority samples could be categorized as CCC. Our
      methods provide a mechanism with which to rank samples and identify those that
      should take the highest priority for return to Earth during a Mars Sample Return
      mission. Key Words: Mars-Astrobiology-Search for Mars' organics-Infrared
      spectroscopy-Planetary habitability and biosignatures. Astrobiology 18, 556-570.

PMID- 29443542
TI  - Comprehensive Analysis of DNA Methylation and Gene Expression Datasets Identified
      MMP9 and TWIST1 as Important Pathogenic Genes of Lung Adenocarcinoma.
AB  - Due to the high mortality of lung cancer, early diagnosis followed by early
      effective treatment is the key to prognosis improvement, which demands to
      identify the biological targets. Therefore, a multistage screening analysis was
      used to identify biological targets of lung adenocarcinoma. Two independent
      datasets of DNA methylation and RNA expression microarray in lung adenocarcinoma
      and normal lung tissues were chosen from the Gene Expression Omnibus. The
      association between DNA methylation and gene expression was explored, and the
      prognostic value of the hub genes was also evaluated. In this study, 8533
      differential methylation sites, mostly located in the CpG island region and
      corresponding to 2754 genes (referred as differential methylation genes), were
      detected from methylation microarray. Besides, we obtained 830 differential
      expression genes, including 570 downregulated and 260 upregulated genes, through
      differential expression analysis. Protein-protein interaction analysis identified
      CXCL12, GFR, KDR, MMP9, TEK, and TWIST as core nodes, involving in the process of
      tumor cell identification, cell growth, cytokine secretion, inflammatory
      response, and angiogenesis. Among them, MMP9 and TWIST1 were identified as more
      valuable biological targets for the early diagnosis and targeted therapy of lung
      cancer through Kaplan-Meier analysis of TCGA lung adenocarcinoma datasets. Our
      study should contribute to the diagnosis and treatment of lung adenocarcinoma.

PMID- 29443543
TI  - ABCB1 1199G > A Polymorphism Impacts Transport Ability of P-gp-Mediated
      Antipsychotics.
AB  - The alterations in P-glycoprotein (P-gp)-mediated transport of antipsychotics due
      to the ABCB1 1199G>A polymorphism were assessed in the current study. The ABCB1wt
      and ABCB11199A recombinant cell models were constructed to study the sensitivity,
      intracellular accumulation, and transepithelial permeability of antipsychotic
      drugs. ABCB11199A recombinant cells had more sensitivity to olanzapine (2.2-fold,
      p < 0.01), aripiprazole (1.8-fold, p < 0.01), amisulpride (2.3-fold, p < 0.01),
      and risperidone (3.1-fold, p < 0.01) than ABCB1wt cells, while the resistance to
      paliperidone in both recombinant cell models was similar. In addition, the uptake
      quality of olanzapine, aripiprazole, amisulpride, and risperidone in ABCB11199A
      recombinant cells was greatly decreased compared to ABCB1wt cells (3.2-fold, p <
      0.01; 3.7-fold, p < 0.01; 3.1-fold, p < 0.01; 2.6-fold, and p < 0.01,
      respectively). Furthermore, apparent permeability values were greatly increased
      in ABCB11199A recombinant cells compared with ABCB1wt recombinant cells for
      olanzapine (2.7-fold, p < 0.01), aripiprazole (2.9-fold, p < 0.01), amisulpride
      (3.4-fold, p < 0.01), and risperidone (4.1-fold, p < 0.01). The influence of
      ABCB1 1199G>A polymorphism on the transport of P-gp-mediated substrates showed up
      as drug-specific. Collectively, the ABCB1 1199G>A polymorphism may impact
      effective antipsychotics concentration in target cells via mediating the agents
      transport and distribution.

PMID- 29443544
TI  - Taste sensitivity to a mixture of monosodium glutamate and inosine 5'
      monophosphate by mice lacking both subunits of the T1R1+T1R3 amino acid receptor.
AB  - The taste of l-glutamate and its synergism with 5'-ribonucleotides is thought to
      be primarily mediated through the T1R1+T1R3 heterodimer in some mammals,
      including rodents and humans. While knockout (KO) mice lacking either receptor
      subunit show impaired sensitivity to a range of monosodium glutamate (MSG)
      concentrations mixed with 2.5 mM inosine 5'-monophosphate (IMP) in amiloride,
      wild-type (WT) controls can detect this IMP concentration, hindering direct
      comparison between genotypes. Moreover, some residual sensitivity persists in the
      KO group, suggesting that the remaining subunit could maintain a limited degree
      of function. Here, C57BL/6J, 129X1/SvJ, and T1R1+T1R3 double KO mice ( n = 16
      each to start the experiment) were trained in a two-response operant task in
      gustometers and then tested for their ability to discriminate 100 uM amiloride
      from MSG (starting with 0.6 M) and IMP (starting with 2.5 mM) in amiloride
      (MSG+I+A). Testing continued with successive dilutions of both MSG and IMP (in
      amiloride). The two WT strains were similarly sensitive to MSG+I+A ( P > 0.8). KO
      mice, however, were significantly impaired relative to either WT strain ( P <
      0.01), although they were able to detect the highest concentrations. Thus, normal
      detectability of MSG+I+A requires an intact T1R1+T1R3 receptor, without regard
      for allelic variation in the T1R3 gene between the WT strains. Nevertheless,
      residual sensitivity by the T1R1+T1R3 KO mice demonstrates that a T1R-independent
      mechanism can contribute to the detectability of high concentrations of this
      prototypical umami compound stimulus.

PMID- 29443546
TI  - Akt1 deficiency diminishes skeletal muscle hypertrophy by reducing satellite cell
      proliferation.
AB  - Skeletal muscle mass is determined by the net dynamic balance between protein
      synthesis and degradation. Although the Akt/mechanistic target of rapamycin
      (mTOR)-dependent pathway plays an important role in promoting protein synthesis
      and subsequent skeletal muscle hypertrophy, the precise molecular regulation of
      mTOR activity by the upstream protein kinase Akt is largely unknown. In addition,
      the activation of satellite cells has been indicated as a key regulator of muscle
      mass. However, the requirement of satellite cells for load-induced skeletal
      muscle hypertrophy is still under intense debate. In this study, female germline
      Akt1 knockout (KO) mice were used to examine whether Akt1 deficiency attenuates
      load-induced skeletal muscle hypertrophy through suppressing mTOR-dependent
      signaling and satellite cell proliferation. Akt1 KO mice showed a blunted
      hypertrophic response of skeletal muscle, with a diminished rate of satellite
      cell proliferation following mechanical overload. In contrast, Akt1 deficiency
      did not affect the load-induced activation of mTOR signaling and the subsequent
      enhanced rate of protein synthesis in skeletal muscle. These observations suggest
      that the load-induced activation of mTOR signaling occurs independently of Akt1
      regulation and that Akt1 plays a critical role in regulating satellite cell
      proliferation during load-induced muscle hypertrophy.

PMID- 29443545
TI  - Ovine uteroplacental and fetal metabolism during and after fetal cortisol
      overexposure in late gestation.
AB  - Cortisol modifies fetal metabolism in preparation for delivery, but whether
      preterm cortisol exposure programs persisting changes in fetoplacental metabolism
      remains unknown. This study infused fetal sheep with saline ( n = 36) or cortisol
      ( n = 27) to raise fetal plasma cortisol to normal prepartum concentrations for 5
      days from day 125 of gestation (term: ~145 days). Fetal uptake and uteroplacental
      metabolism of glucose, oxygen, and lactate, together with fetal hepatic
      glucogenic capacity, were measured on the final day of infusion or 5 days later.
      Cortisol reduced adrenal weight and umbilical glucose uptake during infusion but
      increased fetal glucose concentrations, hepatic glycogen content, and hepatic
      glucogenic enzyme activity (fructose-1,6-bisphosphatase and glucose-6
      phosphatase) and gene expression ( PC and G6PC) compared with saline infusion.
      Postcortisol infusion, umbilical glucose uptake, and hepatic glucose-6
      phosphatase activity remained low and high, respectively, whereas fetal glucose
      levels normalized and hepatic glycogen was lower with higher adrenal weights than
      in controls. Cortisol infusion increased the proportion of total uterine glucose
      uptake consumed by the uteroplacental tissues, irrespective of age. Placental
      tracer glucose transport capacity was also increased after, but not during,
      cortisol infusion, without changes in placental glucose transporter gene
      expression. Blood lactate concentration and Pco2 were higher, whereas pH and O2
      content were lower in cortisol-infused than saline-infused fetuses, although
      uteroplacental metabolism and fetal uptake of oxygen and lactate were unaltered.
      The results suggest that preterm cortisol overexposure alters fetoplacental
      metabolism and adrenal function subsequently with persisting increases in
      uteroplacental glucose consumption at the expense of the fetal supply.

PMID- 29443547
TI  - Modeling heart failure risk in diabetes and kidney disease: limitations and
      potential applications of transverse aortic constriction in high-fat-fed mice.
AB  - There is an increased incidence of heart failure in individuals with diabetes
      mellitus (DM). The coexistence of kidney disease in DM exacerbates the
      cardiovascular prognosis. Researchers have attempted to combine the critical
      features of heart failure, using transverse aortic constriction, with DM in mice,
      but variable findings have been reported. Furthermore, kidney outcomes have not
      been assessed in this setting; thus its utility as a model of heart failure in DM
      and kidney disease is unknown. We generated a mouse model of obesity,
      hyperglycemia, and mild kidney pathology by feeding male C57BL/6J mice a high-fat
      diet (HFD). Cardiac pressure overload was surgically induced using transverse
      aortic constriction (TAC). Normal diet (ND) and sham controls were included.
      Heart failure risk factors were evident at 8-wk post-TAC, including increased
      left ventricular mass (+49% in ND and +35% in HFD), cardiomyocyte hypertrophy
      (+40% in ND and +28% in HFD), and interstitial and perivascular fibrosis
      (Masson's trichrome and picrosirius red positivity). High-fat feeding did not
      exacerbate the TAC-induced cardiac outcomes. At 11 wk post-TAC in a separate
      mouse cohort, echocardiography revealed reduced left ventricular size and
      increased left ventricular wall thickness, the latter being evident in ND mice
      only. Systolic function was preserved in the TAC mice and was similar between ND
      and HFD. Thus combined high-fat feeding and TAC in mice did not model the
      increased incidence of heart failure in DM patients. This model, however, may
      mimic the better cardiovascular prognosis seen in overweight and obese heart
      failure patients.

PMID- 29443548
TI  - Sex- and bone-specific responses in bone structure to exogenous leptin and leptin
      receptor antagonism in the ovine fetus.
AB  - Widespread expression of leptin and its receptor in developing cartilage and bone
      suggests that leptin may regulate bone growth and development in the fetus. Using
      microcomputed tomography, this study investigated the effects of exogenous leptin
      and leptin receptor antagonism on aspects of bone structure in the sheep fetus
      during late gestation. From 125 to 130 days of gestation (term ~145 days),
      chronically catheterized singleton sheep fetuses were infused intravenously for 5
      days with either saline (0.9% saline, n = 13), recombinant ovine leptin at two
      doses (0.6 mg.kg-1.day-1 LEP1, n = 10 or 1.4 mg.kg-1.day-1 LEP2, n = 7), or
      recombinant superactive ovine leptin receptor antagonist (4.6 mg.kg-1.day-1 SOLA,
      n = 6). No significant differences in plasma insulin-like growth factor-I,
      osteocalcin, calcium, inorganic phosphate, or alkaline phosphatase were observed
      between treatment groups. Total femur midshaft diameter and metatarsal lumen
      diameter were narrower in male fetuses treated with exogenous leptin. In a fixed
      length of femur midshaft, total and bone volumes were reduced by the higher dose
      of leptin; nonbone space volume was lower in both groups of leptin-treated
      fetuses. Leptin infusion caused increments in femur porosity and connectivity
      density, and vertebral trabecular thickness. Leptin receptor antagonism decreased
      trabecular spacing and increased trabecular number, degree of anisotrophy, and
      connectivity density in the lumbar vertebrae. The increase in vertebral porosity
      observed following leptin receptor antagonism was greater in the malecompared
      with female, fetuses. Therefore, leptin may have a role in the growth and
      development of the fetal skeleton, dependent on the concentration of leptin, sex
      of the fetus, and bone type examined.

PMID- 29443549
TI  - Endurance exercise training and high-fat diet differentially affect composition
      of diacylglycerol molecular species in rat skeletal muscle.
AB  - Insulin resistance of peripheral muscle is implicated in the etiology of
      metabolic syndrome in obesity. Although accumulation of glycerolipids, such as
      triacylglycerol and diacylglycerol (DAG), in muscle contributes to insulin
      resistance in obese individuals, endurance-trained athletes also have higher
      glycerolipid levels but normal insulin sensitivity. We hypothesized that the
      difference in insulin sensitivity of skeletal muscle between athletes and obese
      individuals stems from changes in fatty acid composition of accumulated lipids.
      Here, we evaluated the effects of intense endurance exercise and high-fat diet
      (HFD) on the accumulation and composition of lipid molecular species in rat
      skeletal muscle using a lipidomic approach. Sprague-Dawley female rats were
      randomly assigned to three groups and received either normal diet (ND) in
      sedentary conditions, ND plus endurance exercise training, or HFD in sedentary
      conditions. Rats were fed ND or HFD between 4 and 12 wk of age. Rats in the
      exercise group ran on a treadmill for 120 min/day, 5 days/wk, for 8 wk. Soleus
      muscle lipidomic profiles were obtained using liquid chromatography/tandem mass
      spectrometry. Total DAG levels, particularly those of palmitoleate-containing
      species, were increased in muscle by exercise training. However, whereas the
      total DAG level in the muscle was also increased by HFD, the levels of DAG
      molecular species containing palmitoleate were decreased by HFD. The
      concentration of phosphatidylethanolamine molecular species containing
      palmitoleate was increased by exercise but decreased by HFD. Our results indicate
      that although DAG accumulation was similar levels in trained and sedentary obese
      rats, specific changes in molecular species containing palmitoleate were
      opposite.

PMID- 29443550
TI  - Erythropoietin, a putative neurotransmitter during hypoxia, is produced in RVLM
      neurons and activates them in neonatal Wistar rats.
AB  - Recent studies indicate that erythropoietin (EPO) is present in many areas of the
      brain and is active in the restoration of impaired neurons. In this study, we
      examined the presence of EPO and its role in bulbospinal neurons in the rostral
      ventrolateral medulla (RVLM). Hypoxia is often accompanied by a high blood
      pressure (BP). We hypothesized that EPO is produced in response to hypoxia in
      RVLM neurons and then activates them. To investigate whether RVLM neurons are
      sensitive to EPO, we examined the changes in the membrane potentials (MPs) of
      bulbospinal RVLM neurons using the whole cell patch-clamp technique during
      superfusion with EPO. A brainstem-spinal cord preparation was used for the
      experiments. EPO depolarized the RVLM neurons, and soluble erythropoietin
      receptor (SEPOR), an antagonist of EPO, hyperpolarized them. Furthermore, hypoxia
      depolarized RVLM neurons were significantly hyperpolarized by SEPOR. In
      histological examinations, the EPO-depolarized RVLM neurons showed the presence
      of EPO receptor (EPOR). The RVLM neurons that possessed EPORs showed the presence
      of EPO and hypoxia-inducible factor (HIF)-2alpha. We also examined the levels of
      HIF-2alpha and EPO messenger RNA (mRNA) in the ventral sites of the medullas
      (containing RVLM areas) in response to hypoxia. The levels of HIF-2alpha and EPO
      mRNA in the hypoxia group were significantly greater than those in the control
      group. These results suggest that EPO is produced in response to hypoxia in RVLM
      neurons and causes a high BP via the stimulation of those neurons. EPO may be one
      of the neurotransmitters produced by RVLM neurons during hypoxia.

PMID- 29443551
TI  - Role of respiration in the cardiovascular response to orthostatic and mental
      stress.
AB  - The objective of this study was to determine the response of heart rate and blood
      pressure variability (respiratory sinus arrhythmia, baroreflex sensitivity) to
      orthostatic and mental stress, focusing on causality and the mediating effect of
      respiration. Seventy-seven healthy young volunteers (46 women, 31 men) aged 18.4
      +/- 2.7 yr underwent an experimental protocol comprising supine rest, 45 degrees 
      head-up tilt, recovery, and a mental arithmetic task. Heart rate variability and
      blood pressure variability were analyzed in the time and frequency domain and
      modeled as a multivariate autoregressive process where the respiratory volume
      signal acted as an external driver. During head-up tilt, tidal volume increased
      while respiratory rate decreased. During mental stress, breathing rate increased
      and tidal volume was elevated slightly. Respiratory sinus arrhythmia decreased
      during both interventions. Baroreflex function was preserved during orthostasis
      but was decreased during mental stress. While sex differences were not observed
      during baseline conditions, cardiovascular response to orthostatic stress and
      respiratory response to mental stress was more prominent in men compared with
      women. The respiratory response to the mental arithmetic tasks was more prominent
      in men despite a significantly higher subjectively perceived stress level in
      women. In conclusion, respiration shows a distinct response to orthostatic versus
      mental stress, mediating cardiovascular variability; it needs to be considered
      for correct interpretation of heart rate and blood pressure phenomena.

PMID- 29443552
TI  - Alamandine acts via MrgD to induce AMPK/NO activation against ANG II hypertrophy
      in cardiomyocytes.
AB  - The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of
      cardiovascular diseases. New members of this system have been characterized and
      shown to have biologically relevant actions. Alamandine and its receptor MrgD are
      recently identified components of RAS. In the cardiovascular system, alamandine
      actions included vasodilation, antihypertensive, and antifibrosis effects.
      Currently, the actions of alamandine on cardiomyocytes are unknown. Here our goal
      was twofold: 1) to unravel the signaling molecules activated by the
      alamandine/MrgD axis in cardiomyocytes; and 2) to evaluate the ability of this
      axis to prevent angiotensin II (ANG II)-induced hypertrophy. In cardiomyocytes
      from C57BL/6 mice, alamandine treatment induced an increase in nitric oxide (NO)
      production, which was blocked by d-Pro7-ANG-(1-7), a MrgD antagonist. This NO
      rise correlated with increased phosphorylation of AMPK. Alamandine-induced NO
      production was preserved in Mas-/- myocytes and lost in MrgD-/- cells. Binding of
      fluorescent-labeled alamandine was observed in wild-type cells, but it was
      dramatically reduced in MrgD-/- myocytes. We also assessed the consequences of
      prolonged alamandine exposure to cultured neonatal rat cardiomyocytes (NRCMs)
      treated with ANG II. Treatment of NRCMs with alamandine prevented ANG II-induced
      hypertrophy. Moreover, the antihypertrophic actions of alamandine were mediated
      via MrgD and NO, since they could be prevented by d-Pro7-ANG-(1-7) or inhibitors
      of NO synthase or AMPK. beta-Alanine, a MrgD agonist, recapitulated alamandine's
      cardioprotective effects in cardiomyocytes. Our data show that alamandine via
      MrgD induces AMPK/NO signaling to counterregulate ANG II-induced hypertrophy.
      These findings highlight the therapeutic potential of the alamandine/MrgD axis in
      the heart.

PMID- 29443553
TI  - Highly conserved motifs within the large Sec7 ARF guanine nucleotide exchange
      factor GBF1 target it to the Golgi and are critical for GBF1 activity.
AB  - Cellular life requires the activation of the ADP-ribosylation factors (ARFs) by
      Golgi brefeldin A-resistant factor 1 (GBF1), a guanine nucleotide exchange factor
      (GEF) with a highly conserved catalytic Sec7 domain (Sec7d). In addition to the
      Sec7d, GBF1 contains other conserved domains whose functions remain unclear.
      Here, we focus on HDS2 (homology downstream of Sec7d 2) domain because the L1246R
      substitution within the HDS2 alpha-helix 5 of the zebrafish GBF1 ortholog causes
      vascular hemorrhaging and embryonic lethality (13). To dissect the
      structure/function relationships within HDS2, we generated six variants, in which
      the most conserved residues within alpha-helices 1, 2, 4, and 6 were mutated to
      alanines. Each HDS2 mutant was assessed in a cell-based "replacement" assay for
      its ability to support cellular functions normally supported by GBF1, such as
      maintaining Golgi homeostasis, facilitating COPI recruitment, supporting
      secretion, and sustaining cellular viability. We show that cells treated with the
      pharmacological GBF1 inhibitor brefeldin A (BFA) and expressing a BFA-resistant
      GBF1 variant with alanine substitutions of RDR1168 or LF1266 are compromised in
      Golgi homeostasis, impaired in ARF activation, unable to sustain secretion, and
      defective in maintaining cellular viability. To gain insight into the molecular
      mechanism of this dysfunction, we assessed the ability of each GBF1 mutant to
      target to Golgi membranes and found that mutations in RDR1168 and LF1266
      significantly decrease targeting efficiency. Thus, these residues within alpha
      helix 2 and alpha-helix 6 of the HDS2 domain in GBF1 are novel regulatory
      determinants that support GBF1 cellular function by impacting the Golgi-specific
      membrane association of GBF1.

PMID- 29443554
TI  - Open Access: Is There a Predator at the Door?

PMID- 29443555
TI  - Three Important Lessons From Research About Sexual and Reproductive Health.

PMID- 29443556
TI  - Supporting Vulnerable Youths Through Community Collaboration.

PMID- 29443557
TI  - Adolescent Pregnancy Prevention Among Youths Living in Group Care Homes: A
      Cluster Randomized Controlled Trial.
AB  - OBJECTIVES: To determine if the Power Through Choices (PTC) intervention can
      increase the use of birth control and reduce pregnancy among system-involved
      youths living in group care homes. METHODS: We performed a 2-arm cluster
      randomized controlled trial involving group care homes operated by child welfare
      or juvenile justice systems in California, Maryland, and Oklahoma with
      assessments immediately before and after the intervention, and at 6- and 12-month
      follow-up. We collected data from 2012 to 2014 via self-administered
      questionnaires. Participants (n = 1036) were young (mean age = 16.1 years),
      predominantly male (79%), racially/ethnically diverse (37% Hispanic, 20% Black,
      21% White, 17% multiracial), and sexually experienced (88%). RESULTS: At 6-month
      follow-up, participants in the intervention group had significantly lower odds of
      having recent sexual intercourse without using birth control (adjusted odds ratio
      [AOR] = 0.72; 95% confidence interval [CI] = 0.52, 0.98). At 12-month follow-up
      assessment, participants in the intervention group had significantly lower odds
      of ever being pregnant or getting someone pregnant (AOR = 0.67; 95% CI = 0.46,
      0.99). CONCLUSIONS: The results suggest that PTC is an effective sexual health
      education intervention that can be implemented with system-involved youths who
      represent a sexually experienced multiracial youth population.

PMID- 29443558
TI  - Reducing Disparities in Adolescent Pregnancy Among US Tribal Youths.

PMID- 29443559
TI  - Considering the Role of Acculturation in Parent-Child Communication About Sexual
      Health.

PMID- 29443560
TI  - Adolescent Pregnancy Prevention in Group Homes: Recruiting and Retention
      Considerations.

PMID- 29443562
TI  - Engaging Young Minority Fathers in Research: Basic Needs, Psychological Needs,
      Culture, and Therapeutic Alliance.

PMID- 29443563
TI  - Decline in Adolescent Pregnancy in the United States: A Success Not Shared by
      All.

PMID- 29443561
TI  - Building Bridges to a Brighter Tomorrow: A Systematic Evidence Review of
      Interventions That Prepare Adolescents for Adulthood.
AB  - BACKGROUND: Data suggest that adverse social determinants during adolescence can
      set in motion a lifetime of poor social and health outcomes. Vulnerable youths
      are at particularly high risk in this regard. OBJECTIVES: To identify and assess
      the current evidence base for adolescent-focused interventions designed to
      influence adulthood preparation that could affect longer-term social
      determinants. SEARCH METHODS: Using a systematic review methodology, we conducted
      an initial assessment of intervention evaluations targeting 6 adulthood
      preparation subject (APS) areas to assess the quality and character of the
      evidence base. The review is specific to evaluated interventions that address at
      least 1 of the 6 APS areas: healthy relationships, adolescent development,
      financial literacy, parent-child communication, educational and career success,
      and healthy life skills. SELECTION CRITERIA: The inclusion criteria were as
      follows: (1) published in English in an independent, peer-reviewed journal; (2)
      conducted in developed, English-speaking countries; (3) implemented an
      intervention that addressed at least 1 of the 6 APS areas, delivered in an in
      person setting; (4) included youths at the 5th- through 12th-grade levels or aged
      10 to 18 years at some point during intervention implementation; (5) included an
      evaluation component with a comparison group and baseline and follow-up measures;
      (6) included behavioral measures as outcomes; and (7) reported statistical
      significance levels for the behavioral outcome measures. DATA COLLECTION AND
      ANALYSIS: We developed an abstraction form to capture details from each article,
      including key details of the intervention, such as services, implementer
      characteristics, and timing; adulthood preparation foci; evaluation design,
      methods, and key behavioral measures; and results, including key statistically
      significant results for behavior-based outcome measures. We assessed study
      quality by using several key factors, including randomization, baseline
      equivalence of treatment and control groups, attrition, and confounding factors.
      We characterized the quality of evidence as high, moderate, or low on the basis
      of the described design and execution of the research. Our assessment included
      only information stated explicitly in the manuscript. MAIN RESULTS: A total of 36
      independent intervention evaluations met the criteria for inclusion. Of these, 27
      (75%) included significant findings for behavioral outcomes related to adulthood
      preparation. Quality was mixed across studies. Of the 36 studies reviewed, 27
      used a randomized controlled design (15 group randomization, 12 individual
      randomization), whereas the others used observational pre-post designs. Ten
      studies used mixed-methods approaches. Most (n = 32) studies used self-report
      questionnaires at baseline with a follow-up questionnaire, and 14 studies
      included multiple follow-up points. Of the studies reviewed, 7 studies received a
      high-quality rating, indicating no significant issues identified within our
      quality criteria. We rated 23 studies as moderate quality, indicating
      methodological challenges within 1 of the quality criteria categories. The most
      common reasons studies were down-rated were poor baseline equivalency across
      treatment groups (or no discussion of baseline equivalency) and high levels of
      attrition. Finally, 6 studies received a low-quality rating because of
      methodological challenges across multiple quality domains. The studies broadly
      represented the APS areas. We identified no systematic differences in study
      quality across the APS areas. AUTHOR'S CONCLUSIONS: Although some of the
      intervention results indicate behavioral changes that may be linked to adulthood
      preparation skills, many of the extant findings are derived from moderate- or
      poor-quality studies. Additional work is needed to build the evidence base by
      using methodologically rigorous implementation and evaluation designs and
      execution. Public Health Implications. Interventions designed to help adolescents
      better prepare for adulthood may have the potential to affect their longer-term
      social determinants of health and well-being. More theory-driven approaches and
      rigorously evaluated interventions could strengthen the evidence base and improve
      the effectiveness of these adulthood preparation interventions.

PMID- 29443564
TI  - Reward Seeking and Self-Regulation: Changing the Environment to Prevent
      Adolescent Pregnancy.

PMID- 29443565
TI  - A Holistic Approach to Adolescent Pregnancy Prevention.

PMID- 29443566
TI  - Is Current Measurement of Contraception Use Hindering Identification of Evidence
      Based Pregnancy Prevention for Vulnerable Adolescents?

PMID- 29443567
TI  - Brief Interpregnancy Interval: Are 75% of Adolescent Mothers Unaware of the
      Prematurity Risk?

PMID- 29443580
TI  - The Mystery of the LUCA: Franklin M. Harold In Search of Cell History: The
      Evolution of Life's Building Blocks.

PMID- 29443568
TI  - Reaching High-Need Youth Populations With Evidence-Based Sexual Health Education
      in California.
AB  - OBJECTIVES: To explore the programmatic reach and experience of high-need
      adolescents who received sexual health education in 3 distinct implementation
      settings (targeted-prevention settings, traditional schools, and alternative
      schools) through a statewide sexual health education program. METHODS: Data are
      from youth surveys collected between September 2013 and December 2014 in the
      California Personal Responsibility Education Program. A sample of high-need
      participants (n = 747) provided data to examine the impact of implementation
      setting on reach and program experience. RESULTS: Implementation in targeted
      prevention settings was equal to or more effective at providing a positive
      program experience for high-need participants. More than 5 times as many high
      need participants were served in targeted-prevention settings compared with
      traditional schools. Reaching the same number of high-need participants served in
      targeted-prevention settings over 15 months would take nearly 7 years of
      programming in traditional schools. CONCLUSIONS: To maximize the reach and
      experience of high-need youth populations receiving sexual health education,
      state and local agencies should consider the importance of implementation
      setting. Targeted resources and efforts should be directed toward high-need young
      people by expanding beyond traditional school settings.

PMID- 29443581
TI  - Erratum.

PMID- 29443582
TI  - Perineural Invasion in Head and Neck Cancer.
AB  - Perineural invasion (PNI) is a mechanism of tumor dissemination that can provide
      a challenge to tumor eradication and that is correlated with poor survival.
      Squamous cell carcinoma, the most common type of head and neck cancer, has a high
      prevalence of PNI. This review provides an overview of clinical studies on the
      outcomes and factors associated with PNI in head and neck cancer and on findings
      on cancer-nerve crosstalk.

PMID- 29443583
TI  - ASCO's Clinical Trials Workshop Increases Clinical Trial Participation at
      Community Practices.

PMID- 29443584
TI  - "The sands are number'd that make up my life..." Shakespeare.

PMID- 29443585
TI  - Fundraising: Serious Focus Proves Vital for Success.

PMID- 29443587
TI  - An Interview With Richard Pazdur, MD.

PMID- 29443586
TI  - ASCO Recommendations on Fertility Preservation in Cancer Patients: Guideline
      Summary.

PMID- 29443588
TI  - Making the Choice Between Academic Oncology and Community Practice: The Big
      Picture and Details About Each Career.

PMID- 29443589
TI  - Oncology Nursing Society: Evidence-Based Practice.

PMID- 29443591
TI  - Sharing PLWC With Your Patients.

PMID- 29443590
TI  - Offering Free Support, Education, and Hope for Cancer Patients and Their
      Caregivers: The Wellness Community.

PMID- 29443592
TI  - Starting Out Right: New Series to Help Oncologists Succeed in Practice Positions.

PMID- 29443593
TI  - Focus on Part D Benefits and Chemotherapy.

PMID- 29443594
TI  - Managing Stress and Burnout in Oncology.

PMID- 29443596
TI  - National Health Accounts: A Framework For Understanding Health Care Financing.
AB  - Over the course of the past century, the challenges facing the United States in
      its consumption of health care goods and services have not changed very much.
      What is being consumed, who is paying for it, and how much is affordable are
      questions that arise in every cycle of the debate-if they ever go dormant.
      National Health Accounts are one tool to use in the search for answers to these
      questions and to the challenges behind the questions. The accounts cannot (and do
      not pretend to) address every aspect of the debate, but they provide an important
      context. In this article I briefly review the history of the health accounts and
      discuss their strengths and weaknesses in the context of the present debate over
      spending.

PMID- 29443597
TI  - What Is The US Health Spending Problem?
AB  - Is increased spending on medical care harmful to the US economy? The overall
      share of the gross domestic product spent on medical care is not a problem,
      provided that the services bought are worth more than their cost. However, high
      and rising costs expose two often-overlooked problems. First, spending is too
      high because many dollars are wasted. Estimates suggest that unnecessary medical
      spending costs the typical American family thousands of dollars each year.
      Second, high medical costs combined with stagnant incomes for a large share of
      the population and the inability of governments at all levels to raise tax
      dollars leads to increased health and economic disparities: fewer people covered
      by private insurance, the rationing of care in public health programs, and the
      lack of funds for other social programs. These distribution issues, coupled with
      the large waste, imply that efforts to address medical spending need to be among
      our highest priorities.

PMID- 29443598
TI  - Evaluation of Natural Product Compositions for Appetite Suppression.
AB  - A change in homeostasis between food intake and energy expenditure is the
      hallmark of obesity. Many plant-based weight-management products are available in
      dietary supplement markets with no direct efficacy comparison. In this in vivo
      acute feed intake study in rats, the appetite suppression efficacy of well-known
      natural ingredients in the weight-loss market were evaluated. We tested pure
      caffeine, potato skin extract, Cissus quadrangularis extract, Garcinia cambogia
      extract, Crocus sativus extract, raspberry ketone isolated from Rubus idaeus, one
      commercial product (Appetrex), and one novel composition (UP601). Rats treated
      with potato skin extract, Crocus sativus bulb extract, and Cissus quadrangularis
      extracts showed statistically significant reduction in food consumption only at
      the 2-hour timepoint with 44.9%, 34.1%, and 44.3% reductions, respectively, after
      food provision at an equivalent human dosage of 2 g, 10 g, and 10 g,
      respectively. Garcinia cambogia fruit extract and raspberry ketone from Rubus
      idaeus showed statistically significant reduction in food consumption only at the
      1-hour timepoint with 33.7% and 79.4% reductions, respectively, after food
      provision at an equivalent human dosage of 8 g and 5 g, respectively. UP601 and
      Appetrex were compared at 230 mg/kg. While 88.5%, 73.8%, and 63.1% reductions in
      food intake were observed for the UP601 treatment group, 64.2%, 27.5%, and 34.7%
      reductions in food intake were observed for rats treated with Appetrex at 1 h, 2
      h, and 4 h after food provision. The composition UP601 demonstrated superior
      activity in food intake compared to any of the dietary supplements marketed for
      appetite suppression tested in this study.

PMID- 29443599
TI  - State Oncology Societies Booth.

PMID- 29443600
TI  - Challenges for Community-Based Clinical Trials.

PMID- 29443601
TI  - What the Multidistrict Litigation Settlements Mean to Your Practice.

PMID- 29443603
TI  - Drug Administration Changes in 2008.

PMID- 29443602
TI  - HIPAA Compliance in Clinical Trials.

PMID- 29443604
TI  - Patient Guides Help Your Patients Understand ASCO Clinical Practice Guidelines.

PMID- 29443605
TI  - ASCO's Commitment to a Better Electronic Health Record-We Need Your Help!

PMID- 29443606
TI  - Put Conflict Resolution Skills to Work.

PMID- 29443608
TI  - ASCO's Library of Treatment Plans and Summaries Expands.

PMID- 29443607
TI  - Medical Group Management Association Assembly of Oncology Hematology
      Administrators ... Who Are We? Why Are We Here?

PMID- 29443609
TI  - The Lance Armstrong Foundation.

PMID- 29443613
TI  - Legislative Outlook: Opportunities and Challenges.

PMID- 29443612
TI  - Elevated Vasodilatory Cyclases and Shorter Telomere Length Contribute to High
      Altitude Pulmonary Edema.
AB  - : Rain, Manjari, Himanshi Chaudhary, Ritushree Kukreti, Tashi Thinlas, Ghulam
      Mohammad, and Qadar Pasha. Elevated vasodilatory cyclases and shorter telomere
      length contribute to high-altitude pulmonary edema. High Alt Med Biol. 19:60-68,
      2018. AIM: High-altitude (HA) genetics is complex with respect to health and
      disease (HA pulmonary edema i.e., HAPE). Based on the widely recognized fact that
      oxidative stress is a major trigger of several physiological processes, this
      study was designed to establish the significance of vasodilatory cyclases and
      telomere length in HA physiology. The study was performed in three groups, namely
      HAPE-free sojourners (HAPE-f, n = 150), HAPE patients (HAPE-p, n = 150), and
      healthy highland natives or highlanders (HLs, n = 150). Variations in soluble
      guanylyl cyclase beta1-subunit (GUCY1B3) and adenylyl cyclase type 6 (ADCY6) were
      genotyped by the SNaPshot method and/or Fluidigm SNP type genotyping. Plasma
      GUCY1B3 and ADCY6 levels were estimated using ELISA, and relative telomere length
      was estimated by qRT-PCR. RESULTS: The rs7638AA genotype was over-represented in
      HLs compared with HAPE-f and HAPE-p (p = 0.035 and p = 0.012, respectively).
      Similarly, the rs7638A allele was prevalent in HLs compared with both groups, but
      significance was attained against HAPE-p (p = 0.012). Significantly elevated
      plasma levels of GUCY1B3 and ADCY6 were obtained in HAPE-p compared with HAPE-f
      (p = 0.001 and p = 0.006, respectively) and HLs (p = 3.31E-05 and p = 0.05,
      respectively). Shorter telomere length was observed in HAPE-p compared with HAPE
      f (p > 0.05) and HLs (p = 0.017). CONCLUSION: Elevated cyclases and shorter
      telomere length associate with HAPE pathophysiology.

PMID- 29443614
TI  - Overview of Medicare Parts A-D.
AB  - With policymakers calling for reforms to ensure Medicare beneficiaries continue
      to have access to care without bankrupting the Medicare Trust Fund, it is hard to
      know how changes to the system will affect cancer care delivery. This primer
      provides oncologists with context for the Medicare reform debates anticipated in
      the coming months.

PMID- 29443615
TI  - Pancreatic Cancer Action Network: Advance Research, Support Patients, and Create
      Hope.
AB  - Pancreatic cancer is the fourth leading cause of death as a result of cancer in
      the United States, and 75% of patients will die within 12 months of diagnosis.
      The Pancreatic Cancer Action Network wants people to know there is hope, and
      there are resources available to help them face this disease.

PMID- 29443616
TI  - Adapting Practice in the Face of New Data.
AB  - Oncologists are often faced with new information on tests, therapies, and
      treatment regimens. Determining how to incorporate that data into practice
      patterns is not easy. Regardless of what motivates you to make a change in
      practice, the explosion of new oncology data demands that you continually
      reevaluate how you practice.

PMID- 29443618
TI  - Personal Finance Management for New Oncologists: Part 2.
AB  - Part two in this two-part series on financial planning for new oncologists looks
      at the basic principles of sound investing in any economic climate.

PMID- 29443617
TI  - Health Insurance and Financial Information for Patients.

PMID- 29443619
TI  - Random Ruminations of a Sports Fan....

PMID- 29443622
TI  - The Role of Extracellular Matrix in Innate Immunity, Fugues of Evolution.

PMID- 29443620
TI  - Transforming Patient Compliance Research in an Era of Biomedicalization.
AB  - The term patient noncompliance emerged in the 1970s as a tool for analyzing why
      people do not follow medical directives. Despite its early popularity, the term
      has languished in sociology while flourishing in biomedical arenas. It seems
      flaccid in a contemporary healthcare context as it overestimates physician
      authority and is tone-deaf to biomedicalization. I draw from sociological and
      anthropological traditions, as well as qualitative interviews with terminally ill
      patients ( N = 26) and their caregivers ( N = 16), to consider facets of a
      biomedicalized health experience and implications for an updated vision of
      compliance. First, pathways to care have proliferated under biomedicalization.
      With increased pathways comes increased need for understanding how treatment
      plans are socially constituted and assessed. Finally, increased complexity
      demands a more diverse vocabulary for understanding health related decisions.
      This paper is a call to sociologists to take the lead in transforming and
      updating this consequential concept.

PMID- 29443626
TI  - Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak -
      Preliminary Report.
AB  - Background In 2016, the response to a yellow fever outbreak in Angola and the
      Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As
      a result, a fractional dose of the 17DD yellow fever vaccine (containing one
      fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years
      of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The
      goal of this study was to assess the immune response to the fractional dose in a
      large-scale campaign. Methods We recruited participants in four age strata at six
      vaccination sites. We assessed neutralizing antibody titers against yellow fever
      virus in blood samples obtained before vaccination and 28 to 35 days after
      vaccination, using a plaque reduction neutralization test with a 50% cutoff
      (PRNT50). Participants with a PRNT50 titer of 10 or higher at baseline were
      considered to be seropositive. Those with a baseline titer of less than 10 who
      became seropositive at follow-up were classified as having undergone
      seroconversion. Participants who were seropositive at baseline and who had an
      increase in the titer by a factor of 4 or more at follow-up were classified as
      having an immune response. Results Among 716 participants who completed follow
      up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after
      vaccination. Among 493 participants who were seronegative at baseline, 482 (98%;
      95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were
      seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response.
      Lower baseline titers were associated with a higher probability of having an
      immune response (P<0.001). Conclusions A fractional dose of the 17DD yellow fever
      vaccine was effective at inducing seroconversion in most of the participants who
      were seronegative at baseline. These findings support the use of fractional-dose
      vaccination for outbreak control. (Funded by the U.S. Agency for International
      Development and the Centers for Disease Control and Prevention.).

PMID- 29443627
TI  - Policy Update: Federal Incentives for the Adoption of Electronic Health Records.
AB  - The American Recovery and Reinvestment Act of 2009 provides financial incentives
      for physicians and hospitals to adopt electronic health records. Practices can
      take initial steps outlined here to receive bonus payments and avoid penalties.

PMID- 29443623
TI  - Calprotectin and the Initiation and Progression of Head and Neck Cancer.
AB  - Calprotectin (S100A8/A9), a heterodimeric complex of calcium-binding proteins
      S100A8 and S100A9, is encoded by genes mapping to the chromosomal locus 1q21.3 of
      the epidermal differentiation complex. Whereas extracellular calprotectin shows
      proinflammatory and antimicrobial properties by signaling through RAGE and TLR4,
      intracytoplasmic S100A8/A9 appears to be important for cellular development,
      maintenance, and survival. S100A8/A9 is constitutively expressed in myeloid cells
      and the stratified mucosal epithelia lining the oropharyngeal and genitourinary
      mucosae. While upregulated in adenocarcinomas and other cancers, calprotectin
      mRNA and protein levels decline in head and neck squamous cell carcinoma (HNSCC).
      S100A8/A9 is also lost during head and neck preneoplasia (dysplasia).
      Calprotectin decrease does not correlate with the clinical stage (TNM) of HNSCC.
      When expressed in carcinoma cells, S100A8/A9 downregulates matrix
      metalloproteinase 2 expression and inhibits invasion and migration in vitro.
      S100A8/A9 regulates cell cycle progression and decelerates cancer cell
      proliferation by arresting at the G2/M checkpoint in a protein phosphatase 2alpha
      dependent manner. In HNSCC, S100A8 and S100A9 coregulate with gene networks
      controlling cellular development and differentiation, cell-to-cell signaling, and
      cell morphology, while S100A8/A9 appears to downregulate expression of invasion-
      and tumorigenesis-associated genes. Indeed, tumor formation capacity is
      attenuated in S100A8/A9-expressing carcinoma cells in vivo. Hence, intracellular
      calprotectin appears to function as a tumor suppressor in head and neck
      carcinogenesis. When compared with S100A8/A9-low HNSCC based on analysis of TCGA,
      S100A8/A9-high HNSCC shows significant upregulation of apoptosis-related genes,
      including multiple caspases. Accordingly, S100A8/A9 facilitates DNA damage
      responses in HNSCC, promotes apoptotic cell death, and confers sensitivity to
      cisplatin and X-radiation in vitro. In the tumor milieu, loss of S100A8/A9
      strongly associates with poor squamous differentiation and higher tumor grading,
      EGFR upregulation, increased DNA methylation, and, finally, poorer overall
      survival for patients with HNSCC. Hence, intracellular calprotectin shows a
      multifaceted protective role against the development of HNSCC.

PMID- 29443629
TI  - Billing for Multiple Injections or Intravenous Pushes of the Same Drug.

PMID- 29443628
TI  - Which Cost Are We Talking About?

PMID- 29443630
TI  - Balancing Your Life at Work and Home.
AB  - The first step in balancing your work and personal life is recognizing that it is
      not just going to happen-you have to be proactive and work at it, and the time to
      do so is now.

PMID- 29443631
TI  - Collaboration.

PMID- 29443632
TI  - Georgia Society of Clinical Oncology Forms a Patient Navigator Affiliate.

PMID- 29443633
TI  - Changes in Medicare Rules Pertaining to Consignment Closets or Stock/Bill
      Arrangements.

PMID- 29443634
TI  - National Health Expenditure Projections, 2017-26: Despite Uncertainty,
      Fundamentals Primarily Drive Spending Growth.
AB  - Under current law, national health spending is projected to grow 5.5 percent
      annually on average in 2017-26 and to represent 19.7 percent of the economy in
      2026. Projected national health spending and enrollment growth over the next
      decade is largely driven by fundamental economic and demographic factors: changes
      in projected income growth, increases in prices for medical goods and services,
      and enrollment shifts from private health insurance to Medicare that are related
      to the aging of the population. The recent enactment of tax legislation that
      eliminated the individual mandate is expected to result in only a small reduction
      to insurance coverage trends.

PMID- 29443636
TI  - ERRATUM.

PMID- 29443635
TI  - Race Differences in Linking Family Formation Transitions to Women's Mortality.
AB  - We examine how the timing and sequencing of first marriage and childbirth are
      related to mortality for a cohort of 4,988 white and black women born between
      1922 and 1937 from the National Longitudinal Survey of Mature Women. We use Cox
      proportional hazard models to estimate race differences in the association
      between family formation transitions and mortality. Although we find no
      relationships between marital histories and longevity, we do find that having
      children, the timing of first birth, and the sequencing of childbirth and
      marriage are associated with mortality. White women who had children lived longer
      than those who had none, but the opposite was found for black women. The effects
      of birth timing also differed by race; delaying first birth to older ages was
      protective for white women but not black women. These results underscore the
      importance of social context in the study of life course transitions.

PMID- 29443637
TI  - The 2011 Electronic Prescribing Incentive Program.

PMID- 29443638
TI  - Human Papillomavirus 16 E6 Induces FoxM1B in Oral Keratinocytes through GRHL2.
AB  - High-risk human papillomavirus (HPV) is a major risk factor for oral and
      pharyngeal cancers (OPCs), yet the detailed mechanisms by which HPV promotes OPCs
      are not understood. Forkhead box M1B (FoxM1B) is an oncogene essential for cell
      cycle progression and tumorigenesis, and it is aberrantly overexpressed in many
      tumors. We previously showed that FoxM1B was the putative target of an epithelial
      specific transcription factor, Grainyhead-like 2 (GRHL2). In the current study,
      we demonstrate that HPV type 16 (HPV-16) E6 induces FoxM1B in human oral
      keratinocytes (HOKs) and tonsillar epithelial cells (TECs) in part through GRHL2.
      FoxM1B was barely detectable in cultured normal human oral keratinocytes (NHOKs)
      and progressively increased in immortalized HOKs harboring HPV-16 genome (HOK
      16B) and tumorigenic HOK-16B/BaP-T cells. Retroviral expression of HPV-16 E6
      and/or E7 in NHOKs, TECs, and hypopharyngeal carcinoma cells (FaDu) revealed
      induction of FoxM1B and GRHL2 by the E6 protein but not E7. Both GRHL2 and FoxM1B
      were strongly induced in the epidermis of HPV-16 E6 transgenic mice and HPV+ oral
      squamous cell carcinomas. Ectopic expression of FoxM1B led to acquisition of
      transformed phenotype in HOK-16B cells. Loss of FoxM1B by lentiviral short
      hairpin RNA vector or chemical inhibitor led to elimination of tumorigenic
      characteristics of HOK-16B/BaP-T cells. Luciferase reporter assay revealed that
      GRHL2 directly bound and regulated the FoxM1B gene promoter activity. Using
      epithelial-specific Grhl2 conditional knockout mice, we exposed wild-type (WT)
      and Grhl2 KO mice to 4-nitroquinolin 1-oxide (4-NQO), which led to induction of
      FoxM1B in the tongue tissues and rampant oral tumor development in the WT mice.
      However, 4-NQO exposure failed to induce tongue tumors or induction of FoxM1B
      expression in Grhl2 KO mice. Collectively, these results indicate that HPV-16
      induces FoxM1B in part through GRHL2 transcriptional activity and that elevated
      FoxM1B level is required for oropharyngeal cancer development.

PMID- 29443644
TI  - Accessing and operating agricultural machinery: Advancements in assistive
      technology for users with impaired mobility.
AB  - This research focused on the advancements made in enabling agricultural workers
      with impaired mobility to access and operate off-road agricultural machinery.
      Although not a new concept, technological advancements in remote-controlled
      lifts, electronic actuators, electric over hydraulic controllers, and various
      modes of hand controls have advanced significantly, allowing operators with
      limited mobility to resume a high level of productivity in agricultural-related
      enterprises. In the United States, approximately 1.7% of the population is living
      with some form of paralysis or significant mobility impairment. When paired with
      the 2012 USDA Agriculture Census of 3.2 million farmers, it can be extrapolated
      that these technologies could impact 54,000 agricultural workers who have
      encountered disabling injuries or disease, which inhibit their ability to access
      and operate tractors, combines, and other self-propelled agricultural machines.
      Advancements in agricultural-specific technologies can allow for many of these
      individuals to regain the ability to effectively operate machinery once more.

PMID- 29443645
TI  - Hair and Salivary Testosterone, Hair Cortisol, and Externalizing Behaviors in
      Adolescents.
AB  - Although testosterone is associated with aggression in the popular imagination,
      previous research on the links between testosterone and human aggression has been
      inconsistent. This inconsistency might be because testosterone's effects on
      aggression depend on other moderators. In a large adolescent sample ( N = 984, of
      whom 460 provided hair samples), we examined associations between aggression and
      salivary testosterone, hair testosterone, and hair cortisol. Callous-unemotional
      traits, parental monitoring, and peer environment were examined as potential
      moderators of hormone-behavior associations. Salivary testosterone was not
      associated with aggression. Hair testosterone significantly predicted increased
      aggression, particularly at low levels of hair cortisol (i.e., Testosterone *
      Cortisol interaction). This study is the first to examine the relationship
      between hair hormones and externalizing behaviors and adds to the growing
      literature that indicates that androgenic effects on human behavior are
      contingent on aspects of the broader endocrine environment-in particular, levels
      of cortisol.

PMID- 29443643
TI  - Comprehensive Examination of the Athlete's Shoulder.
AB  - CONTEXT: Shoulder pain and dysfunction are common, with patients presenting
      complaints to both primary and orthopaedic physicians. History and physical
      examination remain essential to creating a differential diagnosis, even as
      noninvasive imaging has improved. EVIDENCE ACQUISITION: Literature was obtained
      through keyword searches based on the pathology in question (eg, rotator cuff)
      and the keywords physical examination using PubMed from January 1, 1980, through
      September 20, 2017. Additional evidence was obtained through screening references
      from articles identified through the PubMed searches. STUDY DESIGN: Clinical
      review. LEVEL OF EVIDENCE: Level 3. RESULTS: A total of 7817 articles were
      screened for relevance. Several physical examination maneuvers have been
      described for each specific pathology. The Neer sign has a 75% sensitivity for
      subacromial impingement (SAI), while the Hawkins-Kennedy test has an 80%
      sensitivity. The painful arc test has an 80% specificity for SAI. The
      apprehension test has a hazard ratio of 2.96 for anterior shoulder instability.
      The Jobe test has a sensitivity of 52.6% and a specificity of 82.4% for full
      thickness supraspinatus tears, confirmed on arthroscopy. The lag sign is highly
      sensitive and specific for combined full-thickness supraspinatus and
      infraspinatus tears at 97% and 93%, respectively. The Speed test has a
      sensitivity of 54% and specificity of 81% for biceps pathology. The anterior
      slide test and O'Brien active compression test have been described for superior
      labrum anterior posterior tears with inconsistent reliability. The cross-body
      adduction test has a sensitivity of 77% and a specificity of 79% for
      acromioclavicular joint pathology. CONCLUSION: Several physical examination
      maneuvers can isolate specific pathology of the shoulder, with widely ranging
      sensitivity and specificity.

PMID- 29443646
TI  - Electronic Medical Record-Based Radiation Oncology Toxicity Recording Instrument
      Aids Benchmarking and Quality Improvement in the Clinic.
AB  - PURPOSE: The on-treatment visit (OTV) for radiation oncology is essential for
      patient management. Radiation toxicities recorded during the OTV may be
      inconsistent because of the use of free text and the lack of treatment site
      specific templates. We developed a radiation oncology toxicity recording
      instrument (ROTOX) in a health system electronic medical record (EMR). Our aims
      were to assess improvement in documentation of toxicities and to develop clinic
      toxicity benchmarks. METHODS: A ROTOX that was based on National Cancer Institute
      Common Terminology Criteria for Adverse Events (version 4.0) with flow-sheet
      functionality was developed in the EMR. Improvement in documentation was assessed
      at various time intervals. High-grade toxicities (ie, grade >= 3 by CTCAE) by
      site were audited to develop benchmarks and to track nursing and physician
      actions taken in response to these. RESULTS: A random sample of OTV notes from
      each clinic physician before ROTOX implementation was reviewed and assigned a
      numerical document quality score (DQS) that was based on completeness and
      comprehensiveness of toxicity grading. The mean DQS improved from an initial
      level of 41% to 99% (of the maximum possible DQS) when resampled at 6 months post
      ROTOX. This high-level DQS was maintained 3 years after ROTOX implementation at
      96% of the maximum. For months 7 to 9 after implementation (during a 3-month
      period), toxicity grading was recorded in 4,443 OTVs for 698 unique patients; 107
      episodes of high-grade toxicity were identified during this period, and toxicity
      specific intervention was documented in 95%. CONCLUSION: An EMR-based ROTOX
      enables consistent recording of treatment toxicity. In a uniform sample of
      patients, local population toxicity benchmarks can be developed, and clinic
      response can be tracked.

PMID- 29443647
TI  - System-Level Health-Care Integration and the Costs of Cancer Care Across the
      Disease Continuum.
AB  - PURPOSE: Policy reforms in the Affordable Care Act encourage health care
      integration to improve quality and lower costs. We examined the association
      between system-level integration and longitudinal costs of cancer care. METHODS:
      We used linked SEER-Medicare data to identify patients age 66 to 99 years
      diagnosed with prostate, bladder, esophageal, pancreatic, lung, liver, kidney,
      colorectal, breast, or ovarian cancer from 2007 to 2012. We attributed each
      patient to one or more phases of care (ie, initial, continuing, and end of life)
      according to time from diagnosis until death or end of study interval. For each
      phase, we aggregated all claims with the primary cancer diagnosis and identified
      patients treated in an integrated delivery network (IDN), as defined by the
      Becker Hospital Review list of the top 100 most integrated health delivery
      systems. We then determined if care provided in an IDN was associated with
      decreased payments across cancers and for each individual cancer by phase and
      across phases. RESULTS: We identified 428,300 patients diagnosed with one of 10
      common cancers. Overall, there were no differences in phase-based payments
      between IDNs and non-IDNs. Average adjusted annual payments by phase for IDN
      versus non-IDNs were as follows: initial, $14,194 versus $14,421, respectively (
      P = .672); continuing, $2,051 versus $2,099 ( P = .566); and end of life, $16,257
      versus $16,232 ( P = .948). However, in select cancers, we observed lower
      payments in IDNs. For bladder cancer, payments at the end of life were lower for
      IDNs ($11,041 v $12,331; P = .008). Of the four cancers with the lowest 5-year
      survival rates (ie, pancreatic, lung, esophageal, and liver), average
      expenditures during the initial and continuing-care phases were lower for
      patients with liver cancer treated in IDNs. CONCLUSION: For patients with one of
      10 common malignancies, treatment in an IDN generally is not associated with
      lower costs during any phase of cancer care.

PMID- 29443648
TI  - Readmission Patterns After GI Cancer Hospitalizations: The Medical Versus
      Surgical Patient.
AB  - PURPOSE: Readmission within 30 days has been used as a metric for quality of care
      received at hospitals for certain diagnoses. In the era of accountability, value
      based care, and increasing cancer costs, policymakers are looking into cancer
      readmissions as well. It is important to describe the readmission profile of
      patients with cancer in the most clinically relevant approach to inform policy
      and health care delivery that can positively impact patient outcomes. PATIENTS
      AND METHODS: We conducted a retrospective cohort study using linked Texas Cancer
      Registry and Medicare claims data. We included elderly Texas residents diagnosed
      with GI cancer and identified risk factors for unplanned readmission using
      generalized estimating equations, comparing medical with surgical cancer-related
      hospitalizations. RESULTS: We analyzed 69,693 hospitalizations from 31,736
      patients. The unplanned readmission rate was higher after medical
      hospitalizations than after surgical hospitalizations (21.6% v 13.4%,
      respectively). Shared risk factors for readmission after medical and surgical
      hospitalizations included advanced disease stage, high comorbidity index, and
      emergency room visit and radiation therapy within 30 days before index
      hospitalization. Several other associated factors and reasons for readmission
      were noted to be unique to medical or surgical hospitalizations alone.
      CONCLUSION: Unplanned readmissions among elderly patients with GI cancer are more
      common after medical hospitalizations compared with surgical hospitalizations.
      There are shared risk factors and unique risk factors for these hospitalizations
      that can inform policy, health care delivery, and interventions to reduce
      readmissions. Other findings underscore the importance of care coordination and
      comorbidity management in this patient population.

PMID- 29443649
TI  - Use of Charity Financial Assistance for Novel Oral Anticancer Agents.
AB  - Novel oral targeted drugs are increasingly used for cancer therapy, but their
      extreme cost, often exceeding $10,000 per month, poses a significant barrier for
      patients and insurers alike, leading to the potential breakdown of traditional
      cost-sharing strategies. Insured patients' routine use of charity assistance to
      supplement their coverage would indicate a major deficiency in the current health
      care policies. By using data from a specialty pharmacy affiliated with an
      academic center (1,557 prescriptions dispensed between January 2014 and March
      2017), we examined sources of payment for novel oral anticancer agents,
      distinguishing contributions from health insurance, patients, and from charitable
      assistance organizations. Thirty-six percent of 211 patients received charity
      assistance, including 47% of patients who were 65 years old or older. Charity
      sources covered 4% of total drug costs and 64% of out-of-pocket expenditures. The
      proportion of patients receiving financial assistance ranged from 7% when the
      upfront out-of-pocket requirement was less than $100 to 67% when it exceeded
      $1,000. When patients' out-of-pocket requirement exceeded $1,000, the median
      direct cash contribution paradoxically fell to $0 because of extensive use of
      charity support. Receipt of upfront charity assistance was associated with a
      longer time to filling the first prescription (median 9 v 7 days; P = .011) and
      with longer overall duration of therapy (median, 261 v 134 days; P = .014). These
      findings indicate that high out-of-pocket burden for expensive novel oral
      anticancer drugs leads to widespread use of charity support in the United States
      and that a significant financial barrier disparately affects older Medicare
      beneficiaries.

PMID- 29443650
TI  - Open Oncology Notes: A Qualitative Study of Oncology Patients' Experiences
      Reading Their Cancer Care Notes.
AB  - PURPOSE: Electronic medical records increasingly allow patients access to
      clinician notes. Although most believe that open notes benefits patients, some
      suggest negative consequences. Little is known about the experiences of patients
      with cancer reading their medical notes; thus we aimed to describe this
      qualitatively. METHODS: We interviewed 20 adults with metastatic or incurable
      cancer receiving cancer treatment. The semistructured qualitative interviews
      included four segments: assessing their overall experience reading notes,
      discussing how notes affected their cancer care experiences, reading a real note
      with the interviewer, and making suggestions for improvement. We used a constant
      comparison approach to analyze these qualitative data. RESULTS: We found four
      themes. Patients reported that notes resulted in the following: (1) increased
      comprehension; (2) ameliorated uncertainty, relieved anxiety, and facilitated
      control; (3) increased trust; and (4) for a subset of patients, increased
      anxiety. Patients described increased comprehension because notes refreshed their
      memory and clarified their understanding of visits. This helped mitigate the
      unfamiliarity of cancer, addressing uncertainty and relieving anxiety. Notes
      facilitated control, empowering patients to ask clinicians more questions. The
      transparency of notes also increased trust in clinicians. For a subset of
      patients, however, notes were emotionally difficult to read and raised concerns.
      Patients identified medical jargon and repetition in notes as areas for
      improvement. CONCLUSION: Most patients thought that reading notes improved their
      care experiences. A small subset of patients experienced increased distress. As
      reading notes becomes a routine part of the patient experience, physicians might
      want to elicit and address concerns that arise from notes, thereby further
      engaging patients in their care.

PMID- 29443651
TI  - American Society of Clinical Oncology Statement: Biosimilars in Oncology.
AB  - As many biosimilars come to market in the next several years, their use in
      oncology will play an important role in the future care of patients with cancer.
      ASCO is committed to providing education and guidance to the oncology community
      on the use of biosimilars in the cancer setting; therefore, ASCO has developed
      this statement to offer guidance in the following areas: (1) naming, labeling,
      and other regulatory considerations, (2) safety and efficacy of biosimilars, (3)
      interchangeability, switching, and substitution, (4) value of biosimilars, and
      (5) prescriber and patient education.

PMID- 29443652
TI  - Placebo-Controlled, Double-Blinded Phase III Study Comparing Dexamethasone on Day
      1 With Dexamethasone on Days 1 to 3 With Combined Neurokinin-1 Receptor
      Antagonist and Palonosetron in High-Emetogenic Chemotherapy.
AB  - Purpose We evaluated the noninferiority of dexamethasone (DEX) on day 1, with
      sparing on days 2 and 3, combined with neurokinin-1 receptor antagonist (NK1-RA)
      and palonosetron (Palo) compared with the 3-day use of DEX in highly-emetogenic
      chemotherapy (HEC). Patients and Methods Patients who were scheduled to receive
      HEC (cisplatin >= 50 mg/m2 or anthracycline plus cyclophosphamide) were randomly
      assigned to receive either DEX on days 1 to 3 (Arm D3) or DEX on day 1 and
      placebo on days 2 and 3 (Arm D1) combined with NK1-RA and Palo. The primary end
      point was complete response (CR), defined as no emesis and no rescue medications
      during the overall (0 to 120 h) phase. The noninferiority margin was set at 
      15.0% (Arm D1 - Arm D3). Results A total of 396 patients-196 and 200 patients in
      Arms D3 and D1, respectively-were evaluated. CR rates during the overall period
      were 46.9% for Arm D3 and 44.0% for Arm D1 (95% CI, -12.6% to 6.8%; P = .007). CR
      rates during the acute (0 to 24 h) phase were 63.3% and 64.5% for Arms D3 and D1,
      respectively (95% CI, -8.1% to 10.6%; P < .001), and they were 56.6% and 51.5%,
      respectively, during the delayed (24 to 120 h) phase (95% CI, -14.8% to 4.6%; P =
      .023). Hot flushes and tremors were observed more frequently as DEX-related
      adverse events on days 4 and 5 in Arm D3, whereas anorexia, depression, and
      fatigue were observed more frequently on days 2 and 3 in Arm D1. As an indication
      of quality of life, global health status was similar in both arms. Conclusion
      Antiemetic DEX administration on days 2 and 3 can be spared when combined with
      NK1-RA and Palo in HEC.

PMID- 29443654
TI  - Palliative Care Consultation Should Be Routine for All Children Who Enroll in a
      Phase I Trial.

PMID- 29443653
TI  - Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional
      Recurrence of Breast Cancer: Final Analysis of the CALOR Trial.
AB  - Purpose Isolated locoregional recurrence (ILRR) predicts a high risk of
      developing breast cancer distant metastases and death. The Chemotherapy as
      Adjuvant for LOcally Recurrent breast cancer (CALOR) trial investigated the
      effectiveness of chemotherapy (CT) after local therapy for ILRR. A report at 5
      years of median follow-up showed significant benefit of CT for estrogen receptor
      (ER)-negative ILRR, but additional follow-up was required in ER-positive ILRR.
      Patients and Methods CALOR was an open-label, randomized trial for patients with
      completely excised ILRR after unilateral breast cancer. Eligible patients were
      randomly assigned to receive CT or no CT and stratified by prior CT, hormone
      receptor status, and location of ILRR. Patients with hormone receptor-positive
      ILRR received adjuvant endocrine therapy. Radiation therapy was mandated for
      patients with microscopically involved margins, and anti-human epidermal growth
      factor receptor 2 therapy was optional. End points were disease-free survival
      (DFS), overall survival, and breast cancer-free interval. Results From August
      2003 to January 2010, 162 patients were enrolled: 58 with ER-negative and 104
      with ER-positive ILRR. At 9 years of median follow-up, 27 DFS events were
      observed in the ER-negative group and 40 in the ER-positive group. The hazard
      ratios (HR) of a DFS event were 0.29 (95% CI, 0.13 to 0.67; 10-year DFS, 70% v
      34%, CT v no CT, respectively) in patients with ER-negative ILRR and 1.07 (95%
      CI, 0.57 to 2.00; 10-year DFS, 50% v 59%, respectively) in patients with ER
      positive ILRR ( Pinteraction = .013). HRs were 0.29 (95% CI, 0.13 to 0.67) and
      0.94 (95% CI, 0.47 to 1.85), respectively, for breast cancer-free interval (
      Pinteraction = .034) and 0.48 (95% CI, 0.19 to 1.20) and 0.70 (95% CI, 0.32 to
      1.55), respectively, for overall survival ( Pinteraction = .53). Results for the
      three end points were consistent in multivariable analyses adjusting for location
      of ILRR, prior CT, and interval from primary surgery. Conclusion The final
      analysis of CALOR confirms that CT benefits patients with resected ER-negative
      ILRR and does not support the use of CT for ER-positive ILRR.

PMID- 29443655
TI  - Is Interferon-Based Treatment of Viral Hepatitis C Genotype 3 Infection Still of
      Value in the Era of Direct-Acting Antivirals?
AB  - The aim of the study is to analyze treatments available for patients infected
      with genotype (G) 3 hepatitis C virus (HCV) in Poland at the beginning of the
      interferon (IFN)-free era and evaluate the efficacy and safety of different
      therapeutic options administered in a real-world setting. We analyzed data of 198
      patients who started antiviral therapy after July 1, 2015, and completed it
      before December 31, 2016; 57.6% of them had liver cirrhosis and 46% were
      treatment experienced. Fifty percent of patients were assigned to sofosbuvir
      (SOF)+pegylated IFN alfa (PegIFNa)+ribavirin (RBV), 9% to PegIFNa+RBV, 36%
      received SOF+RBV, and 5% SOF+daclatasvir (DCV)+/-RBV. Cirrhotic patients were
      assigned more frequently to IFN-free regimens. Overall, a sustained virological
      response was achieved by 84.3% of patients in intent-to-treat (ITT) analysis and
      87% in modified ITT analysis. For SOF+PegIFNa+RBV and SOF+DCV+/-RBV regimens, the
      sustained virologic response (SVR) rate reached at least 90%, whereas the two
      other therapeutic options demonstrated efficacy <80%. The SVR rate in
      noncirrhotics was higher than in cirrhotics, irrespective of regimen. Adverse
      events were documented in 52.5%, with the most common being weakness/fatigue and
      anemia. We confirmed effectiveness and safety of the SOF-based treatment in a
      real-world cohort of patients with chronic HCV G3 infection. Most notably, we
      demonstrated good tolerability and high efficacy of the SOF+PegIFNa+RBV regimen.

PMID- 29443656
TI  - Highlights for Dengue Immunopathogenesis: Antibody-Dependent Enhancement,
      Cytokine Storm, and Beyond.
AB  - Infection with dengue virus (DENV) can lead to a wide spectrum of clinical
      presentations, ranging from asymptomatic infection to death. It is estimated that
      the disease manifests only in 90 million cases out of the total 390 million
      yearly infections. Even though research has not yet elucidated which are the
      precise pathophysiological mechanisms that trigger severe forms of dengue, the
      infection elicits a critical immune response significant for dengue pathogenesis
      development. Understanding how the immune response to DENV is established and how
      it can resolve the infection or turn into an immunopathology is of great
      importance in DENV research. Currently, studies have extensively debated 2
      hypotheses involving immune response: antibody-dependent enhancement and cytokine
      storm. However, despite its undeniable importance in severe forms of the disease,
      these 2 hypotheses are based on a primed immune status resulting from previous
      heterologous infection, abstaining them from explaining the severe forms of
      dengue in naive immune subjects, for example. Thus, it seems that a more
      intricate arrangement of causes and conditions must be achieved to severe dengue
      to occur. Among them, the cytokine network signature elicited, in association
      with viral aspects deserves special attention regarding the establishment of
      infection and evolution to pathogenesis. In this work, we intend to shed light on
      how those elements contribute to severe dengue development.

PMID- 29443662
TI  - Antiviral Vaccines: Successes and Prospects.

PMID- 29443663
TI  - Innervating Prostate Cancer.

PMID- 29443665
TI  - Phlegmasia Cerulea Dolens with Compartment Syndrome.

PMID- 29443666
TI  - Mepolizumab for Eosinophilic COPD.

PMID- 29443667
TI  - Diuretic Treatment in Heart Failure.

PMID- 29443668
TI  - Medical Devices in the Real World.

PMID- 29443657
TI  - IL-2 and Beyond in Cancer Immunotherapy.
AB  - The development of the T- and natural killer (NK) cell growth factor IL-2 has
      been a sentinel force ushering in the era of immunotherapy in cancer. With the
      advent of clinical grade recombinant IL-2 in the mid-1980s, oncologists could for
      the first time directly manipulate lymphocyte populations with systemic therapy.
      By itself, recombinant IL-2 can induce clinical responses in up to 15% of
      patients with metastatic cancer or renal cell carcinoma. When administered with
      adoptively transferred tumor-reactive lymphocytes, IL-2 promotes T cell
      engraftment and response rates of up to 50% in metastatic melanoma patients.
      Importantly, these IL-2-driven responses can yield complete and durable responses
      in a subset of patients. However, the use of IL-2 is limited by toxicity and
      concern of the expansion of T regulatory cells. To overcome these limitations and
      improve response rates, other T cell growth factors, including IL-15 and modified
      forms of IL-2, are in clinical development. Administering T cell growth factors
      in combination with other agents, such as immune checkpoint pathway inhibitors,
      may also improve efficacy. In this study, we review the development of T- and NK
      cell growth factors and highlight current combinatorial approaches based on these
      reagents.

PMID- 29443669
TI  - Case 5-2018: A 63-Year-Old Man with Confusion after Stem-Cell Transplantation.

PMID- 29443670
TI  - Does CVS-Aetna Spell the End of Business as Usual?

PMID- 29443664
TI  - Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy.
AB  - BACKGROUND: Nusinersen is an antisense oligonucleotide drug that modulates pre
      messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been
      developed for the treatment of spinal muscular atrophy (SMA). METHODS: We
      conducted a multicenter, double-blind, sham-controlled, phase 3 trial of
      nusinersen in 126 children with SMA who had symptom onset after 6 months of age.
      The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal
      administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham
      procedure (control group) on days 1, 29, 85, and 274. The primary end point was
      the least-squares mean change from baseline in the Hammersmith Functional Motor
      Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0
      to 66, with higher scores indicating better motor function. Secondary end points
      included the percentage of children with a clinically meaningful increase from
      baseline in the HFMSE score (>=3 points), an outcome that indicates improvement
      in at least two motor skills. RESULTS: In the prespecified interim analysis,
      there was a least-squares mean increase from baseline to month 15 in the HFMSE
      score in the nusinersen group (by 4.0 points) and a least-squares mean decrease
      in the control group (by -1.9 points), with a significant between-group
      difference favoring nusinersen (least-squares mean difference in change, 5.9
      points; 95% confidence interval, 3.7 to 8.1; P<0.001). This result prompted early
      termination of the trial. Results of the final analysis were consistent with
      results of the interim analysis. In the final analysis, 57% of the children in
      the nusinersen group as compared with 26% in the control group had an increase
      from baseline to month 15 in the HFMSE score of at least 3 points (P<0.001), and
      the overall incidence of adverse events was similar in the nusinersen group and
      the control group (93% and 100%, respectively). CONCLUSIONS: Among children with
      later-onset SMA, those who received nusinersen had significant and clinically
      meaningful improvement in motor function as compared with those in the control
      group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials.gov
      number, NCT02292537 .).

PMID- 29443671
TI  - Initial Treatment of Hypertension.

PMID- 29443672
TI  - Case 31-2017: A 19-Month-Old Girl with Failure to Thrive.

PMID- 29443673
TI  - Edoxaban for the Treatment of Venous Thromboembolism in Patients with Cancer.

PMID- 29443674
TI  - Adjuvant Therapy in Resected Melanoma.

PMID- 29443675
TI  - Prevention of Contrast-Associated Acute Kidney Injury.

PMID- 29443676
TI  - Caring for Ms. L. - Overcoming My Fear of Treating Opioid Use Disorder.

PMID- 29443677
TI  - Drug-Resistant Miliary Tuberculosis in a Child.

PMID- 29443689
TI  - Diagnosis of latent tuberculosis in individuals with recent exposure: tuberculin
      skin test versus interferon-gamma release assay.

PMID- 29443690
TI  - Polycystin-2 is an essential ion channel subunit in the primary cilium of the
      renal collecting duct epithelium.
AB  - Mutations in the polycystin genes, PKD1 or PKD2, results in Autosomal Dominant
      Polycystic Kidney Disease (ADPKD). Although a genetic basis of ADPKD is
      established, we lack a clear understanding of polycystin proteins' functions as
      ion channels. This question remains unsolved largely because polycystins localize
      to the primary cilium - a tiny, antenna-like organelle. Using a new ADPKD mouse
      model, we observe primary cilia that are abnormally long in cells associated with
      cysts after conditional ablation of Pkd1 or Pkd2. Using primary cultures of
      collecting duct cells, we show that polycystin-2, but not polycystin-1, is a
      required subunit for the ion channel in the primary cilium. The polycystin-2
      channel preferentially conducts K+ and Na+; intraciliary Ca2+, enhances its open
      probability. We introduce a novel method for measuring heterologous polycystin-2
      channels in cilia, which will have utility in characterizing PKD2 variants that
      cause ADPKD.

PMID- 29443691
TI  - The effect of emotion on articulation rate in persistence and recovery of
      childhood stuttering.
AB  - PURPOSE: This study investigated the possible association of emotional processes
      and articulation rate in pre-school age children who stutter and persist
      (persisting), children who stutter and recover (recovered) and children who do
      not stutter (nonstuttering). METHODS: The participants were ten persisting, ten
      recovered, and ten nonstuttering children between the ages of 3-5 years; who were
      classified as persisting, recovered, or nonstuttering approximately 2-2.5 years
      after the experimental testing took place. The children were exposed to three
      emotionally-arousing video clips (baseline, positive and negative) and produced a
      narrative based on a text-free storybook following each video clip. From the
      audio-recordings of these narratives, individual utterances were transcribed and
      articulation rates were calculated. RESULTS: Results indicated that persisting
      children exhibited significantly slower articulation rates following the negative
      emotion condition, unlike recovered and nonstuttering children whose articulation
      rates were not affected by either of the two emotion-inducing conditions.
      Moreover, all stuttering children displayed faster rates during fluent compared
      to stuttered speech; however, the recovered children were significantly faster
      than the persisting children during fluent speech. CONCLUSION: Negative emotion
      plays a detrimental role on the speech-motor control processes of children who
      persist, whereas children who eventually recover seem to exhibit a relatively
      more stable and mature speech-motor system. This suggests that complex
      interactions between speech-motor and emotional processes are at play in
      stuttering recovery and persistency; and articulation rates following negative
      emotion or during stuttered versus fluent speech might be considered as potential
      factors to prospectively predict persistence and recovery from stuttering.

PMID- 29443693
TI  - Ketogenic diet in cancer therapy.

PMID- 29443694
TI  - Exploration of two-dimensional bio-functionalized phosphorene nanosheets (black
      phosphorous) for label free haptoglobin electro-immunosensing applications.
AB  - We report on the development of an antibody-functionalized interface based on
      electrochemically active liquid-exfoliated two-dimensional phosphorene (Ph)
      nanosheets-also known as black phosphorous nanosheets-for the label-free
      electrochemical immunosensing of a haptoglobin (Hp) biomarker, a clinical marker
      of severe inflammation. The electrodeposition has been achieved over the screen
      printed electrode (SPE) using liquid-assisted ultrasonically exfoliated black
      phosphorus nanosheets. Subsequently, Ph-SPEs bioconjugated with Hp antibodies
      (Ab), using electrostatic interactions via a poly-L-lysine linker for
      biointerface development. Electrochemical analysis demonstrates that the Ab
      modified Ph-SPEs (Ab@Ph-SPE) exhibit enhanced electroconducting behavior as
      compared to the pristine electrodes. This Ab-functionalized phosphorene-based
      electrochemical immunosensor platform has demonstrated remarkable sensitivity and
      specificity, having a dynamic linear response range from 0.01-10 mg ml-1 for Hp
      in standard and serum samples with a low detection limit (~0.011 mg ml-1) using
      the label-free electrochemical technique. The sensor electrodes were also studied
      with other closely relative interferents to investigate cross reactivity and
      specificity. This strategy opens up avenues to POC (point-of-care) and on-farm
      livestock disease monitoring technologies for multiplexed diagnosis in complex
      biological samples such as serum. The technique is simple in fabrication and
      provides an analytical response in less than 60 s.

PMID- 29443692
TI  - Executive function and childhood stuttering: Parent ratings and evidence from a
      behavioral task.
AB  - PURPOSE: The purpose of this study was to examine the executive function (EF)
      abilities of preschool children who do (CWS) and do not stutter (CWNS) using a
      parent-report questionnaire and a behavioral task. METHOD: Participants were 75
      CWS and 75 CWNS between the ages of 3;0 and 5;11 (years; months). Parents rated
      their children's EF abilities using the Behavioral Rating Inventory of Executive
      Function-Preschool Version (BRIEF-P; Gioia, Espy, & Isquith, 2003). Children's
      ability to integrate cognitive flexibility, inhibitory control, and working
      memory was measured using a behavioral task, the Head-Toes-Knees-Shoulders (HTKS;
      Cameron Ponitz, McClelland, Matthews, & Morrison, 2009). RESULTS: The CWS were
      judged by their parents as being less proficient in working memory,
      shift/flexibility, and overall EF than the parents of the CWNS. Children in the
      CWS group were also 21/2 to 7 times more likely than children in the CWNS group
      to exhibit clinically significant difficulties with EF. Behavioral task findings
      revealed that 3-year old CWS performed more poorly than their peers on the HTKS.
      Parental ratings of executive function and working memory were significantly and
      moderately correlated with receptive and expressive vocabulary skills only for
      the CWNS group. CONCLUSION: CWS have more difficulty with EF in everyday life and
      may experience early delays in their ability to integrate aspects of attention
      and EF compared to CWNS.

PMID- 29443695
TI  - Polarized emission from CsPbBr3 nanowire embedded-electrospun PU fibers.
AB  - Interest in all-inorganic halide perovskites has been increasing dramatically due
      to their high quantum yield, band gap tunability, and ease of fabrication in
      compositional and geometric diversity. In this study, we synthesized several
      hundreds of nanometer long and ~4 nm thick CsPbBr 3 nanowires (NWs). They were
      then integrated into electrospun polyurethane (PU) fibers to examine the
      polarization behavior of the composite fiber assembly. Aligned electrospun fibers
      containing CsPbBr 3 NWs showed a remarkable increase in the degree of
      polarization from 0.17-0.30. This combination of NWs and PU fibers provides a
      promising composite material for various applications such as optoelectronic
      devices and solar cells.

PMID- 29443696
TI  - Intravenous Lidocaine for Intractable Renal Colic Unresponsive to Standard
      Therapy.
AB  - CLINICAL FEATURES: Renal colic is defined as a flank pain radiating to the groin
      caused by kidney stones in the ureter (urolithiasis). Renal colic is a frequent
      cause of Emergency Department visits. Most renal colic cases present as acute
      distress and severe back and/or abdominal pain that require prompt treatment with
      analgesics. THERAPEUTIC CHALLENGE: Nonsteroidal anti-inflammatory drugs and
      opioids are traditionally used for renal colic in the Emergency Department. This
      trend of practice is based on clinical experience and expert opinion. Consensus
      guidelines that provide evidence-based approach for the management of renal colic
      are limited. One consensus guideline from Europe provides a systematic approach
      for the management of pain with the use of nonsteroidal anti-inflammatory drugss
      and opioids. However, no guidance is provided on how to manage patients who do
      not respond to these agents. SOLUTION: Intravenous lidocaine 120 mg in 100 mL
      normal saline was infused over 10 minutes for pain management for intractable
      renal colic unresponsive to standard therapy. Three minutes after initiation of
      lidocaine infusion, the patient reported numeric pain rating scale 1/10. At 5
      minutes, the reported numeric pain rating scale was 0/10 and remained for 60
      minutes after initiation of lidocaine infusion. No adverse events were reported
      during or after the infusion, and no subsequent analgesia was required.

PMID- 29443697
TI  - T-Lymphoblastic Leukemia/Lymphoma With Annular Skin Rash and Epidermotropism.
AB  - Leukemia cutis is uncommon in patients with acute lymphoblastic leukemia. It
      typically presents with dermal papules or subcutaneous nodules, with no epidermal
      or upper papillary dermal involvement on histopathology. We present an unusual
      clinical presentation of leukemia cutis, with annular plaques and
      epidermotropism.

PMID- 29443698
TI  - White-Yellow Papules on the Neck of a Young Woman-Challenge.

PMID- 29443699
TI  - Grover Disease With Epidermal Dysmaturation Pattern: A Common Histopathologic
      Finding.
AB  - BACKGROUND: Grover disease is an entity whose diagnosis is based on
      clinicopathologic correlation. Histopathologically, focal acantholysis is the
      most common finding. In some cases, there is prominent squamous atypia which can
      prove to be very challenging and the lesion may be confused with an epidermal
      neoplasm. OBJECTIVE: To report on atypical histopathological changes in Grover
      disease and to provide helpful clues to differentiate between the epidermal
      atypia seen in some cases of Grover disease and epithelial neoplasms. MATERIAL
      AND METHODS: We analyzed 33 cases of Grover disease histologically diagnosed at
      Wake Forest Baptist Medical Center, NC, between 2011 and 2017. Atypical changes
      in keratinocytes were defined as epithelial buds, nuclear pleomorphism, and
      dyskeratosis in all layers of epidermis or altered granular layer. RESULTS:
      Twenty cases (64%) showed foci with alteration of the normal keratinocytic
      maturation, whereas 18 cases demonstrated nuclear pleomorphism. Buds of
      epithelial cells emanating from the basal layer of the epidermis and granular
      cell alteration was present in 19 cases. CONCLUSIONS: The findings especially the
      presence of an altered granular layer may represent a diagnostic clue in cases of
      Grover disease with atypical changes.

PMID- 29443700
TI  - New Onset Blue-Black Papules in an Older Woman: Question.

PMID- 29443701
TI  - Association of Polypharmacy with Survival, Complications, and Healthcare Resource
      Use after Elective Noncardiac Surgery: A Population-based Cohort Study.
AB  - BACKGROUND: Polypharmacy is increasingly prevalent in older patients and is
      associated with adverse events among medical patients. The impact of polypharmacy
      on outcomes after elective surgery is poorly described. The authors' objective
      was to measure the association of polypharmacy with survival, complications, and
      resource use among older patients undergoing elective surgery. METHODS: After
      registration (NCT03133182), the authors identified all individuals older than 65
      yr old having their first elective noncardiac surgery in Ontario, Canada, between
      2002 and 2014. Using linked administrative data, the authors identified all
      prescriptions dispensed in the 90 days before surgery and classified people
      receiving five or more unique medications with polypharmacy. The associations of
      polypharmacy with 90-day survival (primary outcome), complications, length of
      stay, costs, discharge location, and readmissions were estimated after
      multilevel, multivariable adjustment for demographics, comorbidities, previous
      healthcare use, and surgical factors. Prespecified and post hoc sensitivity
      analyses were also performed. RESULTS: Of 266,499 patients identified, 146,026
      (54.8%) had polypharmacy. Death within 90 days occurred in 4,356 (3.0%) patients
      with polypharmacy and 1,919 (1.6%) without (adjusted hazard ratio = 1.21; 95% CI,
      1.14 to 1.27). Sensitivity analyses demonstrated no increase in effect when only
      high-risk medications were considered and attenuation of the effect when only
      prescriptions filled in the 30 preoperative days were considered (hazard ratio =
      1.07). Associations were attenuated or not significant in patients with frailty
      and higher comorbidity scores. CONCLUSIONS: Older patients with polypharmacy
      represent a high-risk stratum of the perioperative population. However, the
      authors' findings call into question the causality and generalizability of the
      polypharmacy-adverse outcome association that is well documented in nonsurgical
      patients.

PMID- 29443702
TI  - An Automated Segmentation of R2* Iron-Overloaded Liver Images Using a Fuzzy C
      Mean Clustering Scheme.
AB  - OBJECTIVES: The objectives of this study were to develop and test an automated
      segmentation of R2* iron-overloaded liver images using fuzzy c-mean (FCM)
      clustering and to evaluate the observer variations. MATERIALS AND METHODS: Liver
      R2* images and liver iron concentration (LIC) maps of 660 thalassemia
      examinations were randomly separated into training (70%) and testing (30%)
      cohorts for development and evaluation purposes, respectively. Two-dimensional
      FCM used R2* images, and the LIC map was implemented to segment vessels from the
      parenchyma. Two automated FCM variables were investigated using new echo time and
      membership threshold selection criteria based on the FCM centroid distance and
      LIC levels, respectively. The new method was developed on a training cohort and
      compared with manual segmentation for segmentation accuracy and to a previous
      semiautomated method, and a semiautomated scheme was suggested to improve
      unsuccessful results. The automated variables found from the training cohort were
      assessed for their effectiveness in the testing cohort, both quantitatively and
      qualitatively (the latter by 2 abdominal radiologists using a grading method,
      with evaluations of observer variations). A segmentation error of less than 30%
      was considered to be a successful result in both cohorts, whereas, in the testing
      cohort, a good grade obtained from satisfactory automated results was considered
      a success. RESULTS: The centroid distance method has a segmentation accuracy
      comparable with the previous-best, semiautomated method. About 94% and 90% of the
      examinations in the training and testing cohorts were automatically segmented out
      successfully, respectively. The failed examinations were successfully segmented
      out with thresholding adjustment (3% and 8%) or by using alternative results from
      the previous 1-dimensional FCM method (3% and 2%) in the training and testing
      cohorts, respectively. There were no failed segmentation examinations in either
      cohort. The intraobserver and interobserver variabilities were found to be in
      substantial agreement. CONCLUSIONS: Our new method provided a robust automated
      segmentation outcome with a high ease of use for routine clinical application.

PMID- 29443704
TI  - Lateral Collateral Ligament Injury About the Knee: Anatomy, Evaluation, and
      Management.
AB  - The lateral collateral ligament is the primary varus stabilizer of the
      tibiofemoral joint. Diagnosing an injury to this ligament can be challenging in
      the setting of multiligamentous trauma; however, failure to recognize these
      injuries can result in instability of the knee and unsatisfactory outcomes after
      cruciate ligament reconstruction. Recent literature exploring the anatomy and
      biomechanics of the lateral collateral ligament has enhanced our understanding
      and improved diagnosis and management of these injuries. Physical examination and
      imaging studies also are important in diagnosis and can facilitate classification
      of lateral collateral ligament tears, which affects treatment decisions.
      Nonsurgical, reparative, and reconstructive techniques can all be used to manage
      lateral collateral ligament injury about the knee; the optimal treatment is
      selected on the basis of injury severity.

PMID- 29443703
TI  - The Thrower's Shoulder.
AB  - Overhead athletes subject their shoulders to extreme repetitive torque,
      compression, distraction, and translation stresses, resulting in adaptive changes
      of the soft tissues and osseous structures within and around the glenohumeral
      joint. These anatomic adaptations result in biomechanical enhancements, which
      improve performance. Understanding the difference between necessary and adaptive
      changes and pathologic findings is critical when making treatment decisions.
      Injuries to the shoulder of the overhead athlete can be generally classified into
      three groups: internal impingement, internal impingement with acquired secondary
      anterior instability, and primary anterior or multidirectional instability.
      Although advances in surgical techniques have allowed surgeons to address the
      pathology in these groups, merely attempting to restore the shoulder to so-called
      normal can adversely alter adaptive changes that allow high levels of
      performance.

PMID- 29443706
TI  - CASQ1 Gene Is an Unlikely Candidate for Malignant Hyperthermia Susceptibility in
      the North American Population: Erratum.

PMID- 29443705
TI  - Orthopaedic Considerations in the Management of Skeletal Sarcoidosis.
AB  - Advanced imaging has demonstrated that musculoskeletal manifestations of systemic
      sarcoidosis are more common than previously thought. A definitive strategy for
      the management of osseous sarcoidosis has not been defined. Some lesions resolve
      spontaneously, and no systemic medication for sarcoidosis consistently resolves
      lesions. The orthopaedic surgeon treating patients with musculoskeletal
      sarcoidosis must make an appropriate diagnosis of bony lesions, seek
      multidisciplinary input from specialists in pulmonology and rheumatology
      regarding systemic treatment, and decide when surgery is necessary to prevent
      dysfunction.

PMID- 29443707
TI  - Pulmonary Impairment and Risk Assessment in a Diacetyl-Exposed Population:
      Microwave Popcorn Workers.
AB  - OBJECTIVES: The butter flavoring additive, diacetyl (DA), can cause bronchiolitis
      obliterans (BO) by inhalation. A risk assessment was performed using data from a
      microwave popcorn manufacturing plant. METHODS: Current employees' medical
      history and pulmonary function tests together with air sampling over a 2.7-year
      period were used to analyze forced expiratory volume in 1 second (FEV1) and
      FEV1/forced vital capacity (FVC). The exposure responses for declining pulmonary
      function and for possible early onset of BO were estimated using multiple
      regression methods. Several exposure metrics were investigated; benchmark dose
      and excess lifetime risk of impairment were calculated. RESULTS: Forty-six
      percent of the population had less than 6 months exposure to DA. Percent-of
      predicted FEV1 declined with cumulative exposure (0.40 per ppm-yr, P < 10) as did
      percent FEV1/FVC (0.13 per ppm-yr, P = 0.0004). Lifetime respiratory impairment
      prevalence of one per thousand resulted from 0.005 ppm DA and one per thousand
      lifetime incidence of impairment was predicted for 0.002 ppm DA. CONCLUSION: DA
      exposures, often exceeding 1 ppm in the past, place workers at high risk of
      pulmonary impairment.

PMID- 29443708
TI  - Testing the Impact of the Worksite Heart Health Improvement Project on
      Cardiovascular Disease Risk Factors Over Time.
AB  - OBJECTIVE: We aimed to test the impact of the Worksite Heart Health Improvement
      Project (WHHIP) on cardiovascular risk factors among long-term care staff.
      METHODS: The WHHIP was an 18-month cluster randomized control trial conducted in
      four long-term care facilities (n = 98). RESULTS: A significant positive delayed
      intervention effect for diastolic blood pressure was seen in the intervention
      group (80.34 mm/Hg [standard deviation {SD} = 6.10] at baseline to 73.08 mm/Hg
      [SD = 4.99] at 18-months; P = <0.001). Whereas, a significant negative
      intervention effect was seen for steps with a mean increase from 5807.18 (SD =
      3934.30) steps at baseline to 7839.19 (SD = 3126.09) steps at 18-months (P =
      0.022) as well as body mass index with a mean change from 29.86 (SD = 7.38) at
      baseline to 26.67 (SD = 5.29) at 18-months (P = 0.045) in the education only
      group. CONCLUSION: The WHHIP demonstrated the ability to impact participants'
      blood pressure over time.

PMID- 29443709
TI  - General Information on Clinical Psychopharmacology in China.

PMID- 29443711
TI  - Transitions in Training: Teaching Teammates to Use Empowering Language With
      Patients.

PMID- 29443710
TI  - Residency Applications: Overcoming Redundancy With Disclosure.

PMID- 29443712
TI  - A Surgical Transition in Need of Disruption.

PMID- 29443713
TI  - A Program in Transition: A Shifting Mind-set.

PMID- 29443714
TI  - EMT Training as a Transition Into Medical Education.

PMID- 29443715
TI  - The Impact of Frequent Transitions on Families in Medical Training.

PMID- 29443716
TI  - Time for an Acute Focus on Chronic Care in Undergraduate Medical Education.
AB  - As the burdens of chronic disease rise in the United States, both undergraduate
      and graduate medical education must adapt to adequately equip future physicians
      with the skills to manage the increasingly complex health needs affecting the
      population. However, traditional models of undergraduate medical education (UME)
      have made focusing on chronic care education challenging. In this Invited
      Commentary, the authors advocate for strengthening UME based on five approaches
      to engage trainees in learning about chronic care across both the preclinical and
      clinical phases of their education: (1) introducing chronic care in the
      preclinical years; (2) prioritizing chronic care education across all
      specialties; (3) maximizing the fourth year of medical school through a chronic
      care focus; (4) creating chronic-disease-focused advanced clerkships; and (5)
      leveraging technology for education. These five approaches call for restructuring
      of both preclinical and clinical education to more comprehensively emphasize the
      skills and knowledge needed for trainees to manage chronic diseases. Such efforts
      will ensure that graduating medical students are well versed in the competencies
      needed to effectively care for patients with chronic conditions in advance of
      their transition to graduate medical education and clinical practice.

PMID- 29443717
TI  - Anticipating and Training the Physician of the Future: The Importance of Caring
      in an Age of Artificial Intelligence.
AB  - Artificial intelligence and other forms of information technology are only just
      beginning to change the practice of medicine. The pace of change is expected to
      accelerate as tools improve and as demands for analyzing a rapidly growing body
      of knowledge and array of data increase. The medical students of today will
      practice in a world where information technology is sophisticated and
      omnipresent. In this world, the tasks of memorization and analysis will be less
      important to them as practicing physicians. On the other hand, the nonanalytical,
      humanistic aspects of medicine-most importantly, the art of caring-will remain a
      critical function of the physician, and facility with improving systems of care
      will be required. Communication, empathy, shared decision making, leadership,
      team building, and creativity are all skills that will continue to gain
      importance for physicians. These skills should be further prioritized in medical
      school curricula to produce an even more effective physician for the future.

PMID- 29443718
TI  - Reconciling Technology and People: Quality of Care During End-of-Rotation
      Transfers.

PMID- 29443719
TI  - The Time Is Now: Using Graduates' Practice Data to Drive Medical Education
      Reform.
AB  - Medical educators are not yet taking full advantage of the publicly available
      clinical practice data published by federal, state, and local governments, which
      can be attributed to individual physicians and evaluated in the context of where
      they attended medical school and residency training. Understanding how graduates
      fare in actual practice, both in terms of the quality of the care they provide
      and the clinical challenges they face, can aid educators in taking an evidence
      based approach to medical education. Although in their infancy, efforts to link
      clinical outcomes data to educational process data hold the potential to
      accelerate medical education research and innovation. This approach will enable
      unprecedented insight into the long-term impact of each stage of medical
      education on graduates' future practice. More work is needed to determine best
      practices, but the barrier to using these public data is low, and the potential
      for early results is immediate. Using practice data to evaluate medical education
      programs can transform how the future physician workforce is trained and better
      align continuously learning medical education and health care systems.

PMID- 29443720
TI  - Retained Guidewires in the Veterans Health Administration: Getting to the Root of
      the Problem.
AB  - OBJECTIVES: The aims of this study were to investigate the demographics, causes,
      and contributing factors of retained guidewires (GWs) and to make specific
      recommendations for their prevention. METHODS: The Veterans Administration
      patient safety reporting system database for 2000-2016 was queried for cases of
      retained GWs (RGWs). Data extracted for each case included procedure location,
      provider experience, insertion site, urgency, time to discovery, root causes, and
      corrective actions taken. RESULTS: There were 101 evaluable cases of RGWs.
      Resident trainee (36%), critical care unit (38%), femoral vein (44%), and
      nonemergent placement (79%) were the conditions most frequently associated with a
      RGW. While discovery occurred almost immediately (30%) or in next 24 hours (31%),
      there were instances of RGWs found months (2%) or years (3%) later. Common root
      causes included inexperience (46%), lack of standardization (35%), distractions
      (25%), and lack of a checklist (23%). CONCLUSIONS: The results demonstrate the
      result of human factors-based errors such as posttask completion errors. We
      recommend human factor-based interventions such as checklists and devices
      employing forcing functions that do not allow clinicians to complete the
      insertion process without first removing the GW.

PMID- 29443721
TI  - Psychometric Properties of Korean Version of the Second Victim Experience and
      Support Tool (K-SVEST).
AB  - OBJECTIVES: "Second victims" are defined as healthcare professionals whose
      wellness is influenced by adverse clinical events. The Second Victim Experience
      and Support Tool (SVEST) was used to measure the second-victim experience and
      quality of support resources. Although the reliability and validity of the
      original SVEST have been validated, those for the Korean tool have not been
      validated. The aim of the study was to evaluate the psychometric properties of
      the Korean version of the SVEST. METHODS: The study included 305 clinical nurses
      as participants. The SVEST was translated into Korean via back translation.
      Content validity was assessed by seven experts, and test-retest reliability was
      evaluated by 30 clinicians. Internal consistency and construct validity were
      assessed via confirmatory factor analysis. The analyses were performed using SPSS
      23.0 and STATA 13.0 software. RESULTS: The content validity index value
      demonstrated validity; item- and scale-level content validity index values were
      both 0.95. Test-retest reliability and internal consistency reliability were
      satisfactory: the intraclass consistent coefficient was 0.71, and Cronbach alpha
      values ranged from 0.59 to 0.87. The CFA showed a significantly good fit for an
      eight-factor structure (chi = 578.21, df = 303, comparative fit index = 0.92,
      Tucker-Lewis index = 0.90, root mean square error of approximation = 0.05).
      CONCLUSIONS: The K-SVEST demonstrated good psychometric properties and adequate
      validity and reliability. The results showed that the Korean version of SVEST
      demonstrated the extent of second victimhood and support resources in Korean
      healthcare workers and could aid in the development of support programs and
      evaluation of their effectiveness.

PMID- 29443722
TI  - Characterizing Treatment Utilization Patterns for Trigeminal Neuralgia in the
      United States.
AB  - BACKGROUND AND AIM: Trigeminal neuralgia (TN) is a rare orofacial disorder
      characterized by severe unilateral paroxysmal pain in the region of the fifth
      cranial nerve. Clinical guidelines recommend carbamazepine (only US Food and Drug
      Administration-approved drug for TN) and oxcarbazepine as first-line therapies.
      We utilized the US Truven Health MarketScan database to examine treatment
      patterns among patients with TN. METHODS: Included patients were aged 18 years
      and above, newly diagnosed with TN (>=2 TN diagnoses >=14 days apart; no
      diagnosis in the previous year), continuously enrolled 1 year before index, with
      >=3 years' follow-up postindex. We assessed utilization of selected
      pharmacotherapies (carbamazepine, oxcarbazepine, pregabalin, gabapentin,
      baclofen, duloxetine, topiramate), surgery (posterior fossa, radiosurgery), and
      injections (peripheral anesthetic injections, Gasserian ganglion procedures) for
      TN. RESULTS: In total, 3685 patients were included (2425 commercial, 1260
      Medicare; 71.8% female; age, mean [SD], 59 [15] y). Overall, 72.5% of patients
      received at least 1 studied medication, most commonly carbamazepine (51.7%) or
      gabapentin (48.6%). In total, 65% of pharmacologically treated patients had >=2
      treatment episodes; 41.6% had >=3 (defined by a change in pharmacotherapy
      [monotherapy/combination] regimen). Overall, 12.3% had surgery and 7.3%
      injections; 42.9% received opioids for TN. CONCLUSIONS: In the 3 years after
      diagnosis, patients with TN in the United States receive a variety of
      pharmacological treatments, including opioids, despite carbamazepine being the
      only approved medication. A notable proportion utilize surgeries/injections. A
      high proportion of pharmacologically treated patients receive multiple treatment
      episodes, suggesting frequent therapy switching, perhaps because of suboptimal
      efficacy/tolerability. Our data suggest a high burden of illness associated with
      TN.

PMID- 29443723
TI  - Neurophysiological Pain Education for Patients With Chronic Low Back Pain: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To evaluate the effect of neurophysiological pain education (NPE) for
      patients with chronic low back pain (CLBP). METHODS: A systematic search was
      performed in 6 electronic databases. Eligible randomized-controlled trials were
      those with at least 50 % of patients with CLBP and in which NPE was compared with
      no intervention or usual care. Methodological quality was assessed independently
      by 2 of the authors using the Cochrane Collaboration Risk of Bias Tool. The
      effect of NPE was summarized in a random effect meta-analysis for pain,
      disability, and behavioral attitudes. Effect was estimated as weighted mean
      difference (WMD) if outcomes were on the same scale or as standardized mean
      difference (SMD). The overall quality of evidence was evaluated according to
      GRADE guidelines. RESULTS: Seven randomized-controlled trial studies (6 low and 1
      high quality) were included. Statistically significant differences in pain, in
      favor of NPE, were found after treatment, WMD=-1.03 (95% confidence interval
      [CI], -0.55 to -1.52), and after 3 months, WMD=-1.09 (95% CI, -2.17 to 0.00).
      Furthermore statistically significant lower disability was found in the NPE group
      after treatment, SMD=-0.47 (95% CI, -0.80 to -0.13) and after 3 months SMD=-0.38
      (95% CI, -0.74 to -0.02). The difference in favor of NPE in reduction in Tampa
      Scale of Kinesiophobia was not statistically significant, WMD=-5.73 (95% CI, 
      13.60 to 2.14) and after 3 months WMD=-0.94 (95% CI, -6.28 to 4.40). DISCUSSION:
      There was moderate evidence supporting the hypothesis that NPE has a small to
      moderate effect on pain and low evidence of a small to moderate effect on
      disability immediately after the intervention. NPE has a small to moderate effect
      on pain and disability at 3 months follow-up in patients with CLBP.

PMID- 29443724
TI  - Preoperative fasting guidelines in pediatric anesthesia: are we ready for a
      change?
AB  - PURPOSE OF REVIEW: Study after study shows that prolonged fasting before
      anesthesia is common in children. Pediatric anesthesiologists around the world
      are concerned that the current guidelines may be part of the problem. This review
      focuses on what can be done about it. RECENT FINDINGS: We discuss new insights
      into the physiology of gastric emptying of different categories of food and
      drink. The evidence for negative effects of prolonged fasting occurring in spite
      of implementation of the current guidelines is examined. We also critically
      appraise the concept of a strict association between fasting time and the risk of
      aspiration and discuss recent studies in which children have been allowed clear
      fluids less than 2 h before anesthesia induction. SUMMARY: Accumulating evidence
      indicates that changes of the current guidelines for preoperative fasting should
      be considered for children undergoing elective procedures. VIDEO ABSTRACT.

PMID- 29443725
TI  - Pediatric anesthesia after APRICOT (Anaesthesia PRactice In Children
      Observational Trial): who should do it?
AB  - PURPOSE OF REVIEW: This review highlights the requirements for harmonization of
      training, certification and continuous professional development and discusses the
      implications for anesthesia management of children in Europe. RECENT FINDINGS: A
      large prospective cohort study, Anaesthesia PRactice In Children Observational
      Trial (APRICOT), revealed a high incidence of perioperative severe critical
      events and a large variability of anesthesia practice across 33 European
      countries. Relevantly, quality improvement programs have been implemented in
      North America, which precisely define the requirements to manage anesthesia care
      for children. These programs, with the introduction of an incident-reporting
      system at local and national levels, could contribute to the improvement of
      anesthesia care for children in Europe. SUMMARY: The main factors that likely
      contributed to the APRICOT study results are discussed with the goal of defining
      clear requirement guidelines for anesthetizing children. Emphasis is placed on
      the importance of an incident-reporting system that can be used for both
      competency-based curriculum for postgraduate training as well as for continuous
      professional development. Variability in training as well as in available
      resources, equipment and facilities limit the generalization of some of the
      APRICOT results. Finally, the impact on case outcome of the total number of
      pediatric cases attended by the anesthesiologist should be taken into
      consideration along with the level of expertise of the anesthesiologist for
      complex pediatric anesthesia cases.

PMID- 29443726
TI  - Publishing the best basic and applied pain science: open science and PAIN.

PMID- 29443727
TI  - Acute bilateral retina hemorrhages beneath internal limiting membrane: An unusual
      ophthalmological case report of acute leukemia during complete clinical
      remission.
AB  - RATIONALE: Leukemia is a common hematologic disease that causes various systemic
      complications, such as ophthalmological disorders. The venous congestion is
      considered to be the main clinical sign that occurs during the initial stage of
      the disease, whereas white-centered hemorrhages are the most typical
      manifestations in leukemic retinopathy. These complications usually manifest when
      the disease presents with clinical and hematological symptoms. In the present
      study, we report a patient who was diagnosed with leukemic retinopathy. The
      initial signs of this disease were bilateral hemorrhages that occurred during
      complete clinical remission. Previous studies regarding this condition are quite
      rare. PATIENT CONCERNS: We report a 26-year-old man who was diagnosed with
      leukemic retinopathy and exhibited the initial signs of the disease, namely
      bilateral hemorrhages with a distinct appearance beneath the internal limiting
      membrane. In addition, flame-shaped hemorrhages were observed surrounding the
      optic discs and/or along the vessels in the absence of venous congestion. All
      these changes were present during complete clinical remission. DIAGNOSES:
      Bilateral acute leukemic retinopathy, acute lymphoblastic leukemia (pro-B
      lymphocyte, BCR-ABL chimeric gene-positive). INTERVENTIONS: Clinical remission
      was achieved following effective systemic chemotherapy that was applied for
      leukemia in the hematology department. A dynamic observation was applied actively
      in the absence of surgery and/or medical treatment for ophthalmologic treatment.
      OUTCOMES: Best corrected visual acuity was 20/40 in the right eye and 20/60 in
      the left eye, which was considerably better than those noted at the initial visit
      of the patient (20/250 in the right eye and 20/400 in the left eye). LESSONS: The
      cautious expectant treatment is safe and helpful for acute leukemic retinopathy.
      A long-term follow-up is inevitable. Effective systemic chemotherapy that is
      required for leukemia treatment can achieve clinical remission, which might be
      helpful in controlling the pathological changes of the eyes.

PMID- 29443728
TI  - Ultrasound-guided catheterization of the left subclavian vein without recognition
      of persistent left superior vena cava: A case report: Erratum.

PMID- 29443729
TI  - Economic evaluation of weekends-off antiretroviral therapy for young people in 11
      countries: Erratum.

PMID- 29443730
TI  - Prospective associations between measures of gross and fine motor coordination in
      infants and objectively measured physical activity and sedentary behavior in
      childhood: Erratum.

PMID- 29443731
TI  - Recovery of an injured corticofugal tract from the supplementary motor area in a
      patient with traumatic brain injury: A case report.
AB  - RATIONALE: We report on a patient with traumatic brain injury who showed motor
      recovery concurrent with recovery of injured corticofugal tracts (CFTs),
      diagnosed by diffusion tensor tractography (DTT). PATIENT CONCERNS: Four weeks
      after onset, when the patient started rehabilitation, he showed severe weakness
      of both upper and lower extremities [Motricity Index (MI, full score: 100/100):
      9/30]. DIAGNOSES: A 29-year-old male patient underwent conservative management
      for traumatic hemorrhages in both frontal lobes and right thalamus resulting from
      a car accident. INTERVENTIONS: The patient participated in a comprehensive
      rehabilitative management program, including movement therapy, dopaminergic drugs
      for improvement of apraxia (pramipexole: 2.5mg, amantadine: 300mg, ropinirole:
      0.75 mg, and levodopa: 500mg), and neuromuscular electrical stimulation therapy
      of the right elbow extensors, finger extensors, both knee extensors, and ankle
      dorsiflexors. OUTCOMES: After 2 months' intensive rehabilitation, his motor
      weakness rapidly recovered to the point that he was able to move all 4
      extremities against some resistance (MI: 75/75). The right supplementary motor
      area (SMA)-CFT showed narrowing and partial tearing in the upper portion on 1
      month DTT, and became thicker on 3-month DTT. Compared to the 12 normal control
      subjects, the fractional anisotropy (FA) values of the right corticospinal tract
      and both dorsal premotor cortex-CFT were more than 1 standard deviation lower
      than those of normal control subjects on both 1- and 3-month DTTs. LESSONS:
      Although the tract volume of the right SMA-CFT was more than 1 standard deviation
      lower than normal control subjects on 1-month DTT, it increased to within 1
      standard deviation on 3-month DTT. Recovery of the injured SMA-CFT concurrent
      with motor recovery was demonstrated in a patient with traumatic brain injury.

PMID- 29443732
TI  - Curcumin induces apoptosis and inhibits proliferation in infantile hemangioma
      endothelial cells via downregulation of MCL-1 and HIF-1alpha.
AB  - BACKGROUND: Curcumin has been used as an alternative medicine for the treatment
      of infantile hemangiomas (IHs); however, the mechanism underlying the
      effectiveness of curcumin in IHs remains largely unclear. METHODS: In this study,
      we isolated primary human hemangioma endothelial cells (HemECs) from fresh
      surgical specimens of 3 patients. We treated HemECs by curcumin and investigated
      the alterations in proliferative and apoptotic signaling pathways with cell
      counting kit-8, flow cytometry, western blotting, immunofluorescence, and real
      time polymerase chain reaction. RESULTS AND CONCLUSION: We found that curcumin
      potently inhibited proliferation in HemECs, achieving low-micromolar IC50 (the
      half maximal inhibitory concentration) value. We also observed that treatment
      with curcumin induced apoptosis in HemECs, as evidenced by positively Annexin-V
      FITC staining, caspase-3 activation, and cleavage of poly(adenosine diphosphate
      ribose) polymerase (PARP) in the treated cells. Moreover, we showed that curcumin
      suppressed the expression of antiapoptotic protein myeloid cell leukemia-1 (MCL
      1), hypoxia-inducible factor 1alpha (HIF-1alpha), and vascular endothelial growth
      factor (VEGF).Altogether, our study suggests that the effectiveness of curcumin
      in IHs may be associated with its potent antiproliferative and apoptotic
      activities in HemECs.

PMID- 29443733
TI  - Serial evaluation of the SOFA score is reliable for predicting mortality in acute
      severe pancreatitis.
AB  - Acute severe pancreatitis caused high mortality, and several scoring systems for
      predicting mortality are available. We evaluated the effectiveness of serial
      measurement of several scoring systems in patients with acute severe
      pancreatitis.We retrospectively obtained serial measurements of Ranson, Acute
      Physiology and Chronic Health Assessment (APACHE) II, and Sequential Organ
      Failure Assessment (SOFA) scores of 159 patients with acute severe
      pancreatitis.The overall mortality rate was 20%, and early mortality (in the
      first 2 weeks) occurred in 10 (7.4%) patients, while late mortality occurred in
      17 (12.6%).All scoring systems were reliable for predicting overall and intensive
      care unit mortality, while the SOFA score on day 7 presented the largest area
      under the receiver operator characteristic (ROC) curve (0.858, SE 0.055). Changes
      in scores over time were evaluated for predicting the progression of organ
      failure, and the change in SOFA score on hospital day 7 or no interval change in
      SOFA score was associated with higher mortality rates.APACHE II and SOFA scores
      are both sensitive for predicting mortality in acute pancreatitis. The serial
      SOFA scores showed reliable for predicting mortality. Hospital day 7 is a
      reasonable time for SOFA score reassessment to predict late mortality in acute
      severe pancreatitis.

PMID- 29443734
TI  - Prognostic significance of pulmonary hypertension in patients with cystic
      fibrosis: A systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Pulmonary hypertension (PH) is frequently found in
      advanced parenchymal lung diseases like cystic fibrosis (CF), but the role played
      by PH in the clinical outcome of CF patients remains unclear. The aim of this
      study is to determine the influence of PH on survival in the CF population by
      meta-analysis. METHODS: Publications addressing the associations between PH and
      overall survival (OS) or other clinical characteristics in CF patients were
      selected from electronic databases. Odds ratios (ORs) or mean differences (MDs)
      were used to estimate the association between PH and the clinical
      characteristics. The hazard ratios (HRs) with 95% confidence interval (CI) were
      abstracted or calculated to evaluate the association between PH and CF survival
      outcome. Subgroup analyses were also conducted. RESULTS: Seven studies including
      2141 CF patients who met the inclusion criteria were included in our meta
      analysis. With respect to clinical features, PH was significantly associated with
      lower PaO2 (P < .001), higher PaCO2 (P = .02), lower forced expiratory volume in
      1 second percent (P < .001) and lower forced vital capacity percent (P < .001).
      However, PH had no significant impact on CF patients' OS (HR = 1.29, 95% CI 0.81
      to 2.06, P = .283). Furthermore, subgroup analyses also showed no evidence of
      prognostic role of PH in CF patients (all P values >.05). CONCLUSIONS: Our
      findings suggest that the presence of PH was strongly correlated with worse blood
      gas parameters and worse lung function, but surprisingly had no significant
      prognostic value on survival among CF patients. Further large-scale and
      prospective studies are needed to confirm these findings.

PMID- 29443735
TI  - Identification of gene expression models for laryngeal squamous cell carcinoma
      using co-expression network analysis.
AB  - One of the most common head and neck cancers is laryngeal squamous cell carcinoma
      (LSCC). LSCC exhibits high mortality rates and has a poor prognosis. The
      molecular mechanisms leading to the development and progression of LSCC are not
      entirely clear despite genetic and therapeutic advances and increased survival
      rates. In this study, a total of 116 differentially expressed genes (DEGs),
      including 11 upregulated genes and 105 downregulated genes, were screened from
      LSCC samples and compared with adjacent noncancerous. Statistically significant
      differences (log 2-fold difference > 0.5 and adjusted P-value < .05) were found
      in this study in the expression between tumor and nontumor larynx tissue samples.
      Nine cancer hub genes were found to have a high predictive power to distinguish
      between tumor and nontumor larynx tissue samples. Interestingly, they also appear
      to contribute to the progression of LSCC and malignancy via the Jak-STAT
      signaling pathway and focal adhesion. The model could separate patients into high
      risk and low-risk groups successfully when only using the expression level of
      mRNA signatures. A total of 4 modules (blue, gray, turquoise, and yellow) were
      screened for the DEGs in the weighted co-expression network. The blue model
      includes cancer-specific pathways such as pancreatic cancer, bladder cancer,
      nonsmall cell lung cancer, colorectal cancer, glioma, Hippo signaling pathway,
      melanoma, chronic myeloid leukemia, prostate cancer, and proteoglycans in cancer.
      Endocrine resistance (CCND1, RAF1, RB1, and SMAD2) and Hippo signaling pathway
      (CCND1, LATS1, SMAD2, and TP53BP2) could be of importance in LSCC, because they
      had high connectivity degrees in the blue module. Results from this study provide
      a powerful biomarker discovery platform to increase understanding of the
      progression of LSCC and to reveal potential therapeutic targets in the treatment
      of LSCC. Improved monitoring of LSCC and resulting improvement of treatment of
      LSCC might result from this information.

PMID- 29443736
TI  - What may cause fetus loss from acute pancreatitis in pregnancy: Analysis of 54
      cases.
AB  - Acute pancreatitis in pregnancy (APIP) poses a serious threat to the mother and
      her fetus, and might lead to fetal loss including miscarriage and stillbirth in
      certain patients. We sought to identify possible factors that affect fetal
      distress and evaluated outcomes of patients with APIP.We retrospectively reviewed
      clinical records of 54 pregnant women with APIP, who were treated at 2 tertiary
      clinical centers over a 6-year period. Clinical characteristics including
      etiology and severity of APIP, fetal monitoring data, and maternofetal outcomes
      were analyzed.Etiology of APIP included acute biliary pancreatitis (ABP, n = 14),
      hyperlipidemic pancreatitis (HLP, n = 22), and other etiologies (n = 18).
      Severity was classified as mild acute pancreatitis (MAP, n = 23), moderately
      severe acute pancreatitis (MSAP, n = 24), and severe acute pancreatitis (SAP, n =
      7). The incidence of preterm delivery, fetal distress, and fetal loss increased
      with the progression of severity of APIP (P < .05). The severity of HLP was
      significantly higher than that of ABP and APIP of other etiology (P < .01). HLP
      was more likely to lead to fetal distress than other APs (P < .01). Only 12
      (22.2%) patients had fetal monitoring including non-stress test (NST); 1 case of
      SAP (14.3%) and 15 cases of MSAP (62.5%) were not transferred to intensive care
      unit for intensive monitoring.The incidence of fetal distress and fetal loss
      increased with worsening of APIP severity. HLP tends to result in worse fetal
      outcomes. The deficiencies of fetal state monitoring, lack of assessment, and
      management of pregnant women might increase the fetal loss in APIP.

PMID- 29443737
TI  - Effect of tenofovir on renal function in patients with chronic hepatitis B.
AB  - Tenofovir disoproxil fumarate (TDF) is widely used to treat patients with
      hepatitis B virus (HBV) infection. We investigated the effect of TDF on renal
      insufficiency in patients with chronic hepatitis B (CHB).A consecutive cohort
      analysis was applied to CHB patients taking prescribed TDF from January 2012 to
      May 2016 at Soonchunhyang University Seoul Hospital. Alterations over time in
      corrected calcium, phosphate, creatinine, and estimated glomerular filtration
      rate (eGFR) were analyzed using the generalized estimating equation method. The
      percentage increase in creatinine from baseline to the maximum creatinine level
      (delta creatinine) was compared according to the underlying disease using the
      Mann-Whitney U test. Cox proportional hazard regression model was used to
      determine risk factors associated with renal insufficiency.The baseline
      creatinine, eGFR, corrected calcium, and phosphate levels were 0.72 +/- 0.01
      mg/dL (mean +/- SD), 106.37 +/- 1.06 mL/min/1.73 m, 8.82 +/- 0.04 mg/dL, and 3.42
      +/- 0.05 mg/dL, respectively. The creatinine level had increased significantly at
      12, 24, 48, 72, and 96 weeks, while the eGFR level had decreased significantly at
      these 5 time points. Multivariate analysis confirmed that age >=60 years and the
      baseline bilirubin level were independently associated with the risk of renal
      insufficiency. Delta creatinine was significantly higher in patients with
      diabetes mellitus (DM) than in patients without DM.Renal function was decreased
      from baseline in CHB patients receiving TDF therapy, which indicates that the
      renal function of patients undergoing treatment with TDF should be monitored
      regularly. Old age, DM, and serum bilirubin were risk factors for the development
      of renal insufficiency in CHB patients receiving TDF therapy.

PMID- 29443738
TI  - Hodgkin lymphoma involving the tonsil misdiagnosed as tonsillar carcinoma: A case
      report and review of the literature.
AB  - RATIONALE: Primary Hodgkin lymphoma (HL) involving the tonsil is extremely rare.
      Only about 20 such cases with verification of biopsy and immunohistochemistry
      have been reported. Because of its rarity and unremarkable clinical presentation,
      a timely correct diagnosis is very challenging. PATIENT CONCERNS: A 43-year-old
      man complained left tonsillar enlargement and painless masses in left neck, with
      night sweat. The clinical examination found a marked tonsillar asymmetry, with an
      enlarged left tonsil and ipsilateral cervical lymphadenopathy and a normal right
      tonsil. DIAGNOSIS: The patient was initially regarded as tonsillar
      lymphoepithelial carcinoma. INTERVENTIONS: The patient received a resection of
      left tonsil and left cervical masses and then was definitively diagnosed as HL
      (IIEB). He was managed by 6 cycles of chemotherapy (adriamycin, bleomycin,
      vinblastine, and dacarbazine) and radiotherapy to the Waldeyer ring. OUTCOMES:
      The patient has been disease free for more than 3 years after diagnosis. LESSONS:
      As the reason of an extreme rare occurrence of HL involving the tonsil, doctors
      can easily misdiagnose the disease as tonsillar lymphoepithelial carcinoma. This
      case serves as a reminder important role of biopsy.

PMID- 29443739
TI  - Effects of exercise on secretion transport, inflammation, and quality of life in
      patients with noncystic fibrosis bronchiectasis: Protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Bronchiectasis is characterized by pathological and irreversible
      bronchial dilatation caused by the inefficient mucus and microorganism clearance
      and progression of inflammatory processes. The most frequent characteristic is
      the increase in bronchial mucus production resulting in slower transport and
      damage to the mucociliary transport. AIMS: To evaluate the effects of exercise on
      mucus transport, inflammation, and resistance of the respiratory and autonomic
      nervous systems and subsequent effects on quality of life in patients with
      bronchiectasis who are enrolled in a pulmonary rehabilitation program. METHODS:
      Sixty subjects of both sexes between 18 and 60 years (30 volunteers with
      clinically stable bronchiectasis and 30 healthy volunteers) will be included.
      Participants with chronic obstructive pulmonary disease, decompensated
      cardiovascular or metabolic diseases, neuromuscular and musculoskeletal diseases,
      and active smokers will be excluded. Volunteers will be randomly allocated to the
      pulmonary rehabilitation or control groups. The primary outcomes will be nasal
      transport time as evaluated by nasal saccharin transport time, analysis of nasal
      lavage, enzyme immunoassay of exhaled expiration, and analysis of the mucus
      properties. The secondary outcomes will include pulmonary function tests, impulse
      oscillometry, heart rate variability analysis, and quality of life
      questionnaires. DISCUSSION: In addition to the benefits for patients already
      described in the literature, the additional benefit of mucus removal may
      contribute to optimizing treatments and better control of the disease.
      CONCLUSION: This protocol could provide new information about the unclear
      mechanisms regarding exercise to aid in the removal of secretions.

PMID- 29443740
TI  - Clinical outcomes of left main coronary artery disease patients undergoing three
      different revascularization approaches.
AB  - Significant unprotected left main (LM) coronary artery disease is frequently
      associated with severe multivessel disease and increased mortality and morbidity
      compared with non-LM coronary artery disease. This study compared the clinical
      outcomes of patients with LM disease who received percutaneous coronary
      intervention (PCI) with stenting, conventional coronary-artery bypass grafting (C
      CABG), and robot-assisted CABG (R-CABG).This retrospective study analyzed 472
      consecutive LM disease patients who underwent three different revascularization
      approaches at a tertiary medical center between January 2005 and November 2013.Of
      the 472 LM disease patients, 139 received R-CABG, 147 received C-CABG, and 186
      received PCI. The need for target vessel revascularization (TVR) was highest in
      the PCI group. The R-CABG group had significantly lower rates of in-hospital and
      follow-up all-cause deaths compared with the other 2 groups (1.4% vs. 3.4% and
      9.7%, P = .0058; 13.7% vs. 29.3% and 29.6%, P = .0023, respectively). Patients in
      the R-CABG group had significantly lower rates of intra-aortic balloon pump
      assistance, and shorter duration of ICU and total hospital stay compared to
      patients in the C-CABG group. However, revascularization modality, SYNTAX scores,
      and residual SYNTAX scores were not independent predictors of in-hospital or long
      term mortality.In this cohort of LM disease patients treated at a tertiary
      medical center, PCI is a reasonable choice in patients with less lesion
      complexity but who are older and have comorbidities. R-CABG is feasible in stable
      LM disease patients with high SYNTAX scores, and is an effective alternative to C
      CABG in LM disease patients with few risk factors. However, revascularization
      modality per se was not a determinant for long-term mortality in our real-world
      practice.

PMID- 29443741
TI  - Research progress of asymptomatic bacteriuria before arthroplasty: A systematic
      review.
AB  - BACKGROUND: A high prevalence of asymptomatic bacteriuria exists in patients
      prior to arthroplasty, and urinary tract infection is considered to be a source
      of postoperative superficial wound and prosthetic joint infections. There is no
      consensus whether to screen for and treat asymptomatic bacteriuria before
      arthroplasty. OBJECTIVE: To summarize the association between asymptomatic
      bacteriuria and complications after arthroplasty and to evaluate the clinical
      benefits of treating asymptomatic bacteriuria prior to arthroplasty. METHOD: We
      systematically searched PubMed, Embase, and the Cochrane Library to retrieve
      potentially eligible articles. By screening the titles and abstracts of retrieved
      records and then reading the full texts of the remaining papers, we finally
      included 8 English-language articles in this systematic review. RESULTS:
      Asymptomatic bacteriuria prior to arthroplasty is significantly associated with
      an increased occurrence of postoperative prosthetic joint and superficial wound
      infections. However, there is little evidence for direct or hematogenous seeding
      of urinary infections, and treating asymptomatic bacteriuria before arthroplasty
      did not decrease the incidence of postoperative infectious complications.
      CONCLUSION: Asymptomatic bacteriuria is not a contraindication for arthroplasty,
      and the practice of routine preoperative screening for and treatment of
      asymptomatic bacteriuria should not be continued.

PMID- 29443742
TI  - Ghost cell odontogenic carcinoma with suspected cholesterol granuloma of the
      maxillary sinus in a patient treated with combined modality therapy: A case
      report and the review of literature.
AB  - RATIONALE: Ghost cell odontogenic carcinoma (GCOC) is a rare malignant
      odontogenic tumor with aggressive growth characteristics. PATIENT CONCERNS: A 41
      year-old Chinese male visited our hospital in 2013, with a 4-month history of
      bloody purulent rhinorrhea with a peculiar smell in the right nasal cavity.
      DIAGNOSES: The patient suffered from recurrent GCOC with suspected cholesterol
      granuloma of the maxillary sinus. The patient was incorrectly diagnosed with a
      calcifying epithelial odontogenic tumor at his first recurrence. Physical
      examination, radiological examination, and histopathology were used to identify
      GCOC. INTERVENTIONS: Considering the recurrence of GCOC and poor effects of
      single surgery, postoperative adjuvant chemotherapy and concurrent
      chemoradiotherapy were performed after radical surgical excision. OUTCOMES: So
      far, no significant evidence has suggested recurrence or metastasis after a long
      term follow-up. LESSONS: We advocate wide surgery with clean margins at the first
      accurate diagnosis. Combined modality therapy could be taken for the recurrent
      GCOC. We expect to provide a new treatment strategy to prevent the growth of this
      neoplasm.

PMID- 29443743
TI  - Circulating miR-146a/b correlates with inflammatory cytokines in COPD and could
      predict the risk of acute exacerbation COPD.
AB  - The aim of this study was to investigate the predicting value of miR-146a/b for
      acute exacerbation chronic obstructive pulmonary disease (AECOPD) and COPD, and
      to explore their associations with inflammatory cytokines in AECOPD and stable
      COPD patients.One hundred six AECOPD, 122 stable COPD patients, and 110 health
      volunteers with age and sex matched to total COPD patients (AECOPD and stable
      COPD) were enrolled. Blood samples were collected from all participants. Relative
      expression of miR-146a/b was determined by real-time polymerase chain reaction.
      Tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta),
      interleukin-6 (IL-6), interleukin-8 (IL-8), leukotriene B4 (LTB-4) expression in
      serum from AECOPD and stable COPD patients were assessed using commercial ELISA
      kit.Serum levels of miR-146a and miR-146b were down regulated in AECOPD patients
      compared with stable COPD patients and HCs. miR-146a and miR-146b are of good
      values for predicting the risk of AECOPD in HCs with AUC of 0.702 and 0.715.
      Additionally, miR-146a and miR-146b could distinguish AECOPD from stable COPD
      patients with AUC of 0.670 and 0.643. In AECOPD patients, levels of miR-146a in
      AECOPD patients were negatively associated with TNF-alpha, IL-6, IL-8, and LTE-4
      expression. In stable COPD patients, miR-146a expressions were negatively
      correlated with TNF-alpha, IL-1beta, IL-6, IL-8, and LTE-4 levels. And, the
      expressions of miR-146b in AECOPD patients were negatively associated with IL
      1beta and LTB-4 expression. While in stable COPD patients, miR-146b expressions
      were only negatively correlated with TNF-alpha level.In conclusion, miR-146a and
      miR-146b were negatively correlated with inflammatory cytokines, and could be
      promising biomarkers for predicting the risk of AECOPD in stable COPD patients
      and healthy individuals.

PMID- 29443744
TI  - Serum levels of vitamin A and 25-hydroxyvitamin D3 (25OHD3) as reflectors of
      pulmonary function and quality of life (QOL) in children with stable asthma: A
      case-control study.
AB  - BACKGROUND: This study aims to explore the relationship between serum vitamin A
      and 25-hydroxyvitamin D3 (25OHD3) levels with pulmonary function and quality of
      life (QOL) in children with stable asthma. METHODS: A total of 117 cases of
      children with stable asthma were assigned into the case group and 129 healthy
      children underwent physical examination during the same period into the control
      group. Electrochemiluminescence was employed to determine serum vitamin A and
      25OHD3 levels. The children with stable asthma were further divided into the
      mild, moderate, and severe groups according to their degree of asthma. A
      pulmonary function meter was used to assess the pulmonary function indexes:
      percentage of forced expiratory volume in 1 sec/predictive value (FEV1%pred),
      forced vital capacity (FVC), forced expiratory volume in 1 sec/forced vital
      capacity (FEV1/FVC), peak expiratory flow (PEF), and maximal voluntary
      ventilation (MVV). The children's quality (QOL) of life with asthma was evaluated
      by their activities of daily living (ADLs) and Medical Research Council (MRC)
      scores. Pearson correlation analysis was applied to analyze the correlations of
      serum vitamin A and 25OHD3 levels with FEV1%pred, FVC, FEV1/FVC, PEF, MVV, ADL,
      and MRC. RESULTS: Serum vitamin A and 25OHD3 levels were lower in children with
      stable asthma than those who were in the control group (P < .05). The severe
      group showed the lowest FEV1%pred, FVC, FEV1/FVC, PEF, MVV, and ADL scores, and
      the highest MRC score compared to the mild and moderate groups (all P < .05).
      Serum vitamin A and 25OHD3 levels were positively correlated with pulmonary
      function and ADL score in children with stable asthma, while serum vitamin A and
      25OHD3 levels were negatively correlated with MRC score (all P < .05). In the
      case group, serum vitamin A and 25OHD3 levels were positively correlated with
      serum calcium and phosphorus levels (all P < .05). CONCLUSION: These findings
      indicate that increased serum vitamin A and 25OHD3 levels reflect good pulmonary
      function and good QOL in children with stable asthma.

PMID- 29443745
TI  - Laparoscopic left lateral hepatic sectionectomy was expected to be the standard
      for the treatment of left hepatic lobe lesions: A meta-analysis.
AB  - BACKGROUND: Laparoscopic left lateral hepatic sectionectomy (LLLHS) has been
      widely accepted because of the benefits of minimally invasive surgery. We aimed
      to assess the benefits and drawbacks of left lateral sectionectomy (of segments
      II/III) compared with laparoscopic and open approaches. METHODS: Relevant
      literature was searched using the PubMed, Embase, Cochrane, and Ovid Medline
      databases. We calculated odds ratios or mean differences with 95% confidence
      intervals (CIs) for fixed-effects and random-effects models. RESULTS: The meta
      analysis included 14 trials involving 685 patients. There were no statistically
      significant differences between LLLHS and open LLHS (OLLHS) regarding analgesia
      (P = .31), pedicle clamping (P = .70), operative time (P = .54), hospital
      expenses (P = .64), postoperative alanine aminotransferase levels (P = .57),
      resection margin (95% CI -3.02-4.28; P = .73), or tumor recurrence (95% CI 0.51
      3.05; P = .62). However, the LLLHS group showed significantly better results
      regarding blood transfusion (95% CI 0.14-0.73; P = .007), blood loss (95% CI 
      140.95 to -67.23; P <.001), total morbidity (95% CI 0.24-0.56; P <.01), and
      hospital stay (95% CI -3.84 to -2.31; P <.001) than the OLLHS group. CONCLUSION:
      LLLHS has an advantage in the hospital stay, blood loss, and total morbidity. It
      is an ideal method for LLHS surgery.

PMID- 29443746
TI  - Platelet count to spleen thickness ratio is related to histologic severity of
      primary biliary cholangitis.
AB  - The aim of this study was to evaluate the ability of noninvasive markers to
      identify the histological severity of primary biliary cholangitis (PBC).Fifty
      eight treatment-naive PBC patients who had undergone liver biopsy were enrolled
      in our study. The patients' histological stages were based on the classifications
      of Ludwig and Scheuer. Aspartate aminotransferase-to-platelet ratio index (APRI),
      fibrosis index based on the 4 factors (FIB-4), red blood cell distribution width
      to platelet ratio (RPR), and platelet count to spleen thickness (PC/ST) ratio
      were calculated. Using the area under the receiver operating characteristic curve
      (AUROC) to evaluate the accuracy of different markers for predicting the
      histological severity.Among the 58 treatment-naive PBC patients, the patients of
      Scheuer stage I/II/III/IV were 17/25/11/5, respectively. PC/ST ratio (AUROC =
      0.807) was superior to RPR (AUROC = 0.717), APRI (AUROC = 0.726), FIB-4 (AUROC =
      0.722), and mean platelet volume (MPV) (AUROC = 0.671) in discriminating between
      stage I and stage >=II. The AUROC of PC/ST ratio, RPR, APRI, FIB-4, and MPV were
      0.939, 0.872, 0.816, 0.831 and 0.572, respectively, for Scheuer stage >=III;
      0.968, 0.795, 0.744, and 0.723, respectively for stage IV. The sensitivity and
      specificity of PC/ST ratio were 73.4%,79.1%; 81%,100%;88.7%,100% for detection of
      Scheuer stage >= II, Scheuer stage >= III and Scheuer stage IV, respectively.Our
      study findings indicated that compared with previous noninvasive test PRP, APRI,
      FIB-4 and MPV, PC/ST ratio shows the most accurate for distinguish the histologic
      severity of PBC patients.

PMID- 29443747
TI  - Supraglottoplasty in neonates and infants: A radiofrequency ablation approach.
AB  - BACKGROUND: Supraglottoplasty is the mainstay of surgical treatment for
      laryngomalacia. A novel supraglottoplasty surgical technique is needed to achieve
      better efficacy. The purpose of this study was to introduce modified microscopic
      radiofrequency ablation supraglottoplasty (MMRAS) for the treatment of congenital
      laryngomalacia and to evaluate the outcome and effectiveness of this novel
      approach. METHODS: Seventeen children with severe laryngomalacia who underwent
      MMRAS were studied retrospectively. Supraglottoplasty of type III laryngomalacia
      was different from classical method. All the patients were kept intubated for 5
      days after surgery to achieve a better epiglottal position and to avoid
      reconglutination of aryepiglottic folds. The patients' demographic information,
      symptoms, comorbidities, type of laryngomalacia, synchronous airway lesions and
      final outcomes were examined. RESULTS: The median age at the time of surgery was
      3.36 months (3 months 10 days). Operative indications included feeding
      difficulties, noisy breathing or respiratory distress (or both), and sleep
      related symptoms. The MMRAS success rate was 82.4%. Most patients were extubated
      successfully on postoperative day 5. The major postoperative complication was
      pulmonary infection which occurred in 3 cases (17.6%) and required anti-infective
      therapy. No perioperative deaths and no long-term complications occurred.
      Failures were observed in 3 (17.6%) of 17 cases, 2 patients presented with a
      neurological disease and required tracheostomy, 1 patient relapsed because of
      postoperative adhesions and later underwent revision supraglottoplasty.
      CONCLUSIONS: From these results, we conclude that MMRAS is an effective and safe
      treatment for symptomatic laryngomalacia and has the potential to provide better
      breathing, feeding, and sleeping outcomes in children with severe laryngomalacia.
      Postoperative intubation for 5 days may result in better therapeutic outcomes.
      Multicenter cooperative studies of comparison between MMRAS and conventional
      approaches would lend further evidence-based support for this surgical method.

PMID- 29443748
TI  - Ultrasound combined with fine needle aspiration cytology for the assessment of
      axillary lymph nodes in patients with early stage breast cancer.
AB  - This study aimed to explore the clinical usefulness of ultrasound-guided fine
      needle aspiration cytology (USG-FNAC) for the evaluation of axillary lymph nodes
      in patients with early stage breast cancer (BC) among the Chinese Han female
      population.Around 124 patients with early stage BC were included in this
      retrospective study. All patients underwent USG-FNAC (group A). Patients with
      proven metastasis also underwent axillary lymph node dissection (ALND) (group B).
      In addition, sentinel lymph node biopsy (SLNB) was performed 2 to 5 hours prior
      to the surgery.The sensitivity, specificity, accuracy, and positive predictive
      value (PPV) of axillary ultrasound were 75.0%, 75.0%, 75.0%, and 82.6%,
      respectively, while for USG-FNAC, they were 80.8%, 100.0%, 88.7%, and 100.0%,
      respectively. Significant differences were found in specificity, accuracy, and
      PPV between the 2 procedures (P < .05).The results of this study demonstrated
      that USG-FNAC was effective for selecting patients with early stage BC using ALND
      or SLNB among the Chinese Han female population.

PMID- 29443749
TI  - Usefulness of the maximum standardized uptake value for the diagnosis and staging
      of patients with cervical cancer undergoing positron emission tomography/computed
      tomography.
AB  - Cervical cancer recently has become more common among younger women in Japan.
      Diagnosing early-stage cancer is straightforward using cervical cytodiagnosis and
      histological diagnosis. However, postmenopausal endophytic cervical cancer and
      skip lesions in cervical adenocarcinoma are difficult to detect. We compared the
      maximum standardized uptake value (SUVmax) of 18F-fluorodeoxy-glucose positron
      emission tomography/computed tomography (PET/CT) for primary staging of cervical
      cancer and evaluated the relationship of the imaging findings to prognosis.This
      was a retrospective study of 38 patients with cervical cancer who underwent
      PET/CT. Patients were grouped according to disease stage, and the mean SUVmax,
      overall survival, and progression-free survival (PFS) were evaluated.The mean
      SUVmax was significantly different between patients with stage <=I and >=II
      diseases among those with squamous (P > .001) and glandular (P = .023) lesions.
      With an SUVmax of receiver operating characteristic curves as the optimal cutoff
      value, the log-rank test for PFS revealed a statistically significant difference
      between the 2 disease stages (P = .020 and P = .016, respectively).SUVmax is
      useful to differentiate between stage <=I and >=II cervical cancer. SUVmax may be
      useful for the prognostic evaluation of disease recurrence in patients with
      cervical cancer.

PMID- 29443750
TI  - Effect and safety of roflumilast for chronic obstructive pulmonary disease in
      Chinese patients.
AB  - BACKGROUND: This trial aimed to evaluate the efficacy and safety of roflumilast
      for treating Chinese patients with chronic obstructive pulmonary disease (COPD).
      METHODS: A total of 120 patients with COPD were recruited and were randomly
      divided into 2 groups (an intervention group and a placebo group) at a 1:1 ratio.
      Patients received either roflumilast or placebo 500 MUg once daily for a total of
      12 months. The primary outcome was lung function, measured by the change from
      baseline of forced expiratory volume in 1 second (FEV1), FVC = forced vital
      capacity (FVC), and FEF25-75%. The secondary outcome measurements included the
      quality of life, measured with the St. George's Respiratory Questionnaire (SGRQ).
      All outcomes were measured at the end of 12-month treatment and 3-month follow-up
      after the treatment. In addition, adverse events (AEs) were also recorded during
      the treatment period. RESULTS: FEV1, FVC, FEF25-75%, and SGRQ were significantly
      better in the intervention group than those in the placebo group at the end of 12
      month treatment and 3-month follow up after treatment. Moreover, AEs were much
      higher with roflumilast than placebo in this study. CONCLUSIONS: The findings
      suggest that roflumilast has promising effect to improve lung function in Chinese
      population with COPD.

PMID- 29443751
TI  - A case report of rectal schwannoma treated with laparoscopic proctectomy.
AB  - RATIONALE: Schwannomas of gastrointestinal tracts are rare and difficult to
      detect preoperatively because of negative results of endoscopic and imaging
      examinations. Here, we reported a case of rectal schwannoma, which was diagnosed
      by immunohistochemical staining after laparoscopic protectomy. PATIENT CONCERNS:
      A 61-year-old woman complained of a 1-month history of difficulty in defecation
      and irregularly abdominal discomfort during her physical checkup in our hospital.
      DIAGNOSES: Immunohistochemical staining results after laparoscopic protectomy
      revealed a strong positive reaction for S-100 protein. Therefore, rectal
      schwannoma was confirmed. INTERVENTIONS: Treatment with laparoscopic protectomy
      was given. OUTCOMES: Symptoms resolved completely after 12 days of the surgery,
      and was regular followed-up in outpatient clinic. LESSONS: Schwannomas are
      difficult to identify preoperatively, and immunohistochemical staining for S-100
      protein is an effective method to diagnose it.

PMID- 29443752
TI  - The first case report of Enterococcus gallinarum meningitis in neonate: A
      literature review.
AB  - RATIONALE: Enterococcus gallinarum meningitis (EGM) is rarely found in normal
      adults and even rarer in children. To our knowledge, EGM in neonate has not been
      reported previously. PATIENTS CONCERNS: Here we reported the first case of EGM in
      neonate. Prolonged fever was the only manifestation for the case after admission.
      DIAGNOSES: Cerebrospinal fluid cultures showed that the isolate was Enterococcus
      gallinarum and sensitive to linezolid. INTERVENTIONS: Ceftriaxone, beta lactam
      type, and vancomycin were used respectively, but not effective. OUTCOMES: The
      temperature went down to normal after linezolid was used and the baby was
      discharged in good condition in the end. LESSONS: This case indicated that EGM
      could also occur in neonate and fever could be the only obvious manifestation.
      Thus, the effective antibiotics and adequate duration are very important and
      linezolid is a potential good choice, especially for vancomycin-resistant
      patients.

PMID- 29443753
TI  - Intense 18F-FDG activity in aortoiliac bypass graft mimicking infection: A case
      report.
AB  - RATIONALE: F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed
      tomography (PET/CT) has the potential to become an important imaging tool for the
      diagnosis of suspected aortoiliac bypass graft infection (AGI). PATIENT CONCERNS:
      A 76-year-old man presented with incidental findings of intense F-FDG activity in
      previous operation site of aortobiiliac bypass graft in the initial staging of
      small cell lung cancer (SCLC). DIAGNOSES: Based on F-FDG PET/CT examination,
      preliminary differential diagnosis was AGI. INTERVENTIONS: We performed
      laboratory tests and Galliun-citrate (Ga) single photon emission computed
      tomography/computed tomography (SPECT/CT). OUTCOMES: He had no constitutional
      symptoms and abnormal laboratory test results suggesting AGI. CT scan of the
      abdomen and pelvis showed no abnormal findings. Also, Ga planar scintigraphy and
      SPECT/CT imaging of the abdomen and pelvis failed to show abnormal Ga uptake in
      the same site of aortobiiliac bypass graft with F-FDG uptake. LESSONS: We present
      a case with postoperative inflammatory aortobiiliac bypass graft which was
      misdiagnosed as AGI based on intense F-FDG activity seen at PET/CT imaging.

PMID- 29443754
TI  - Multiple extra-articular synovial cysts accompanied by rheumatoid arthritis in
      the bilateral elbow joints: A case report.
AB  - RATIONALE: Synovial cysts are well known in rheumatoid arthritis (RA), and most
      common in the popliteal fossa. They may produce lots of local symptoms and
      complaints, which may present initially as an unrelated clinical condition. Few
      studies have reported multiple extra-articular synovial cysts (MESCs) in the RA
      patients. Early diagnosis is crucial for patient treatment. PATIENT CONCERNS: A
      50-year-old man without any special clinical histories found a soya bean size
      bump at the left elbow medially, then multiple lumps were found at bilateral
      elbows and gradually increasing. No pain, no activity, no redness, and swelling.
      Magnetic resonance imaging (MRI) showed multiple cystic lesions in the bursa and
      surrounding soft tissue of bilateral elbow joints. In addition, the elbow joint
      bursa was swollen and the synovial membrane was significantly thickened.
      DIAGNOSES: The man was diagnosed as RA with multiple extra-articular synovial
      cysts formation. INTERVENTIONS: The patient was performed tylectomy of the right
      elbow. Other lumps were punctured and injected with compound betamethasone
      injection. OUTCOMES: The bumps were reduced in size and the swelling relieved,
      and the patient was sent to the department of rheumatology and immunology for
      further treatment. LESSONS: In this case, it is difficult for the diagnosis of RA
      because of no relative histories and simultaneously multiple cystic lesions in
      multiple joints. Imaging examinations can show the characteristics of such kind
      of disease and be very helpful for the diagnosis and differentiate diagnosis.

PMID- 29443755
TI  - Argininemia as a cause of severe chronic stunting and partial growth hormone
      deficiency (PGHD): A case report.
AB  - RATIONALE: Argininemia is an autosomal recessive inherited disorder of the urea
      cycle. Because of its atypical symptoms in early age, diagnosis can be delayed
      until the typical chronic manifestations - including spastic diplegia,
      deterioration in cognitive function, and epilepsy - appear in later childhood.
      PATIENT CONCERNS: A Chinese boy initially presented with severe stunting and
      partial growth hormone deficiency (PGHD) at 3 years old and was initially treated
      with growth hormone replacement therapy. Seven years later (at 10 years old), he
      presented with spastic diplegia, cognitive function lesions, epilepsy, and
      peripheral neuropathy. DIAGNOSES: Ultimately, the patient was diagnosed with
      argininemia with homozygous mutation (c.32T>C) of the ARG1 gene at 10 years old.
      Blood tests showed mildly elevated blood ammonia and creatine kinase, and
      persistently elevated bilirubin. INTERVENTIONS: Protein intake was limited to 0.8
      g/kg/day, citrulline (150-200 mg [kg d]) was prescribed. OUTCOMES: The patient's
      mental state and vomiting had improved after 3 months treatment. At 10 years and
      9 month old, his height and weight had reached 121cm and 22kg, respectively, but
      his spastic diplegia symptoms had not improved. LESSONS: This case demonstrates
      that stunting and PGHD that does not respond to growth hormone replacement
      therapy might hint at inborn errors of metabolism (IEM). IEM should also be
      considered in patients with persistently elevated bilirubin with or without
      abnormal liver transaminase, as well as elevated blood ammonia and creatine
      kinase, in the absence of hepatic disease.

PMID- 29443756
TI  - Ulcerative colitis followed by the development of typical intestinal Behcet
      disease: A case report.
AB  - RATIONALE: Intestinal Behcet disease (intestinal BD) and inflammatory bowel
      disease (IBD) share a lot of characteristics, including genetic background,
      clinical manifestations, and therapeutic strategies, especially the
      extraintestinal manifestations, such as oral ulcers, arthralgia, eye lesions,
      skin lesions, etc, but the coexistence of these 2 diseases are uncommon. Behcet
      disease with gastrointestinal involvement in ulcerative colitis (UC) patient has
      been reported in just 1 previous case report, but, which can not be diagnosed as
      definite intestinal BD based on Korean novel diagnositic criteria due to lacking
      the typical ileocecal ulcer. PATIENT CONCERNS: We present a 23-year-old woman
      with ulcerative disease who developed typical intestinal BD, which is the first
      case report of patient with coexisting UC and typical intestinal BD. DIAGNOSES:
      This patient was diagnosed as coexistence of intestinal BD and UC base on the
      clinical manifestations, extra intestinal manifestations and typical colonoscopic
      findings. INTERVENTIONS: Steroid and methotrexate were administered. OUTCOMES:
      This patient achieved clinical remission and mucosal healing. LESSONS:
      Coexistence of intestinal BD and UC is uncommon, and the combination with
      steroid, methotrexate, and 5-aminosalicylic acids is an effective therapy.

PMID- 29443757
TI  - Various surgical techniques to create an aesthetic appearance at the donor site
      of anterolateral thigh free flaps based on the oblique branch: Twenty-one
      clinical case reports.
AB  - RATIONALE: Reducing the morbidity associated with anterolateral thigh (ALT) donor
      sites by performing aesthetic restoration has become a popular research topic.
      Various surgical techniques have been developed allowing for direct closure of
      the donor site. However, closure techniques for ALT donor sites based on the
      oblique branch have not been systematically reported. PATIENT CONCERNS: Data from
      21 patients (18 males, 3 females) undergoing operative reconstruction with an ALT
      free flap between January 2016 and December 2016. The mean age of the
      participants was 42 years (range, 18-60 years). DIAGNOSES: The soft-tissue
      defects resulted from a traffic accident in 9 patients, a fall injury in 7
      patients, a machinery injury in 3 patients, an electrical injury in 1 patient,
      and a burn scar in 1 patient. The wound areas ranged from 6 * 3.5 to 28 cm * 10
      cm. INTERVENTIONS: Several surgical techniques, including the split skin paddle
      technique and utilization of an adjacent perforator flap or an ipsilateral groin
      flap, were utilized to facilitate direct closure of the ALT flap donor site.
      OUTCOMES: Of the 21 patients included in the study, the donor sites were directly
      sutured in 14 patients (8 of which required a split skin paddle technique). Four
      patients required an adjacent perforator flap, and 3 patients received an
      ipsilateral groin flap. The size of the adjacent perforator flaps ranged from 15
      * 5 to 17 * 6 cm. The groin flaps ranged from 18 * 6 to 28 * 6 cm. All the flaps
      had excellent appearance and texture. A linear scar in the donor area was not
      conspicuous and achieved an aesthetic appearance. LESSONS: The ALT flap donor
      site based on the oblique branch pedicle can be directly closed without skin
      grafts through the use of several surgical techniques.

PMID- 29443758
TI  - A novel arthroscopic all-inside suture technique using the Fast-Fix 360 system
      for repairing horizontal meniscal tears in young athletes: 3 case reports.
AB  - RATIONALE: Considering the risk of osteoarthritis following resection of a
      horizontally torn meniscus of the knee, repairing and preserving the meniscus as
      much as possible is preferred. We report 3 cases of restoration of horizontally
      torn menisci using a novel arthroscopic method we have called "all-inside
      interleaf vertical suture" that afforded preservation. PATIENT CONCERNS: The 3
      patients (aged 14, 17, and 21 years) had knee pain through sports activity.
      DIAGNOSES: All patients had horizontal tears in the posteromedial part of the
      meniscus. INTERVENTIONS: The method uses Fast-Fix, whereby a first anchor is
      inserted from the tibial surface of the tear's superior leaflet and a second
      anchor is inserted from the femoral surface of the tear's inferior leaflet, and
      the 2 leaflets are closed using vertical suture. In all cases, the suture knots
      were embedded between the superior leaflet and inferior leaflet, avoiding contact
      with the articular cartilage, and superior leaflet and inferior leaflet crimping
      was good. OUTCOMES: All 3 were able to resume competing in sport and >= 1 year
      after surgery they had no pain and their postoperative mean Lysholm scores were
      99.7. There were no complications or recurrence. On magnetic resonance imaging,
      the signal intensity of all the horizontal tears was high before surgery but low
      after surgery, suggesting that the repaired tear was healing. LESSONS: The all
      inside interleaf vertical suture procedure is a new surgical technique that can
      repair posteromedial horizontal meniscal tears of the knee of young people by
      easy crimping of the superior and inferior leaflets without the suture knots
      causing complications.

PMID- 29443759
TI  - A traumatic hepatic artery pseudoaneurysm and arterioportal fistula, with severe
      diarrhea as the first symptom: A case report and review of the literature.
AB  - RATIONALE: Hepaticarterioportal fistula (APF) is a rare cause of portal
      hypertension and gastrointestinal hemorrhage, and presents as abnormal
      communication between the hepatic artery and portal vein. Percutaneous liver
      biopsy is a main iatrogenic cause of AFP. However, non-iatrogenic, abdominal,
      trauma-related APF is rarely reported. PATIENT CONCERNS: A 29-year-old man
      presenting with severe, watery diarrhea was transferred to our hospital, and his
      condition was suspected to be acute gastroenteritis because he ate expired food
      and suffered a penetrating abdominal stab wound 5 years ago. After admission, the
      patient suffered from hematemesis, hematochezia, ascites, anuria, and kidney
      failure, and he developed shock. DIAGNOSES: The patient was finally diagnosed as
      a traumatic hepatic artery pseudoaneurysm and APF. INTERVENTIONS: This patient
      was treated with emergency transarterial embolization using coils. Since a
      secondary feeding vessel was exposed after the first embolization of the main
      feeding artery, a less-selective embolization was performed again. OUTCOMES:
      During the 6-month follow-up period, the patient remained asymptomatic. LESSONS:
      A penetrating abdominal stab wound is a rare cause of hepatic APFs, and
      occasionally leads to portal hypertension, the medical history and physical
      examination are the most important cornerstones of clinical diagnosis.
      Interventional radiology is essential for the diagnosis and treatment of an APF.

PMID- 29443760
TI  - Resection of benign side-branch intraductal papillary mucinous neoplasm of the
      pancreas-is long term follow-up indicated?: A case report and review of the
      literature.
AB  - RATIONALE: Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are
      benign cystic tumors with a relevant risk of malignant transformation over time.
      Currently, follow-up after surgical resection of benign IPMNs remains
      controversial. PATIENT CONCERNS: This is a case report of a 68-year-old male who
      underwent pancreatic head resection for a multicystic side-branch IPMN with low
      grade epithelial dysplasia in March 2009 at the Katharinenhospital Stuttgart,
      Germany. DIAGNOSES: During postoperative follow-up, a new solid, slightly
      hypodense lesion in the tail of the pancreas measuring 2.4 cm in diameter was
      diagnosed in July 2016. Preoperative staging revealed no signs of distant
      metastasis. INTERVENTION: Subsequently, the patient underwent pancreatic tail
      resection including splenectomy. Histology revealed IPMN-associated
      adenocarcinoma of the pancreas pT3, pN1 (2/24), M0, R0. OUTCOMES: Patients with
      IPMN bare a relatively high overall risk of developing pancreatic cancer. The 5
      year incidence has been described to be as high as 6.9%. The current Consensus
      Guidelines therefore recommend a structural life-time follow-up. In contrast, in
      2015 the American Gastroenterological Association (AGA) explicitly states that
      follow-up is not recommended for resected benign IPMN. Currently, a general and
      international consensus is lacking. LESSONS: The presented case demonstrates that
      even more than 5 years following resection of benign IPMN, pancreatic cancer can
      occur in a separate location of the pancreatic gland. We believe that IPMNs can
      be considered as indicator lesions for pancreatic cancer. Patients with resected
      side-branch IPMN should therefore undergo long term follow-up.

PMID- 29443761
TI  - Haemolytic-uremic syndrome due to infection with adenovirus: A case report and
      literature review.
AB  - RATIONALE: Haemolytic-uremic syndrome is a rare but serious complication of
      bacterial and viral infections, which is characterized by the triad of: acute
      renal failure, microangiopathic haemolytic anemia and thrombocytopenia, sometimes
      severe, requiring peritoneal dialysis. In Europe, hemolytic-uremic syndrome (HUS)
      in paediatric pathology is primarily caused by Shiga toxin-producing Escherichia
      coli (STEC) O157, followed by O26. Beside these etiologies, there are other
      bacterial and viral infections, and also noninfectious ones that have been
      associated to lead to HUS as well: in the progression of neoplasia, medication
      related, post-transplantation, during pregnancy or associated with the
      antiphospholipid syndrome, systemic lupus erythematosus or family causes with
      autosomal dominant or recessive inheritance. In terms of pathogenesis, HUS is the
      result of endothelial injury, most commonly being a result of the action of Shiga
      toxin. The unfavorable prognosis factors being represented by the age of more
      than 5 years old, different etiologies from STEC, persistent oligoanuria, central
      nervous system and glomerular impairment, the association of fever with
      leukocytosis. HUS is responsible for 7% of cases of hypertension in infants, and
      an important cause of significant kidney damage in adults. PATIENT CONCERNS: We
      present one case of HUS caused by adenovirus in a boy of 1 year and 7 months old
      with severe evolution, which required peritoneal dialysis. DIAGNOSE: Stool sample
      repeated examination for adenovirus antigen was positive in 2 samples.
      INTERVENTION: During hospitalization, the patient required 8 peritoneal dialysis
      sessions. OUTCOME: The renal function was corrected on discharge, the patient
      required cardiovascular monitoring 1 month after discharge. LESSON: Although the
      most common cause that leads to HUS remains STEC, other etiologies like viral
      ones that may be responsible for severe enteric infection with progression into
      HUS should not be neglected.

PMID- 29443762
TI  - Incidence and risk factors for surgical site infection after open reduction and
      internal fixation of ankle fracture: A retrospective multicenter study.
AB  - : Information on surgical site infection (SSI) after surgical treatment of ankle
      fracture is limited and remains controversial. The purpose of the present study
      was to determine the incidence and risk factors for SSI after open reduction and
      internal fixation (ORIF) of ankle fracture. Patients who underwent ORIF for ankle
      fracture at 3 centers between January 2015 and December 2016 were included. The
      potential risk factors for SSI included demographic variables, including age,
      sex, body mass index (BMI), hypertension, diabetes mellitus, heart disease,
      smoking, and excessive alcohol intake; blood test variables including
      preoperative white blood cell count, neutrophil count, red blood cell count,
      hemoglobin, total protein, albumin and globulin; injury- and surgery-related
      variables, including duration of operation (minutes), intraoperative blood loss,
      surgeon level, fracture site, accompanied dislocation, use of a drainage tube,
      and antibiotic use. Factors related with SSI occurrence were investigated by
      univariate analysis, and then by multivariate analysis. During hospitalization,
      4.37% (66/1511) of patients developed SSI, which was deep in 1.32% (20/1510) and
      superficial in 3.05% (46/1510). The most common causative agent was polymicrobial
      (causing approximately half of all SSIs), followed by methicillin-resistant
      Staphylococcus aureus (MRSA). Multivariate analysis revealed that the significant
      risk factors for SSI occurrence were open injury, advanced age, incision
      cleanliness II - IV, high-energy injury, more experienced surgeon level, greater
      BMI, chronic heart disease, history of allergy, and preoperative neutrophil count
      > 75%. Preoperative preventative measures should be taken in patients with these
      conditions to lower the incidence of SSI after ORIF of ankle fracture. LEVEL OF
      EVIDENCE: Level III - Retrospective Comparative Study.

PMID- 29443763
TI  - Epibulbar complex cartilaginous choristoma: A distinctive clinicopathological
      case series and literature review.
AB  - To newly describe the clinical and histopathological characteristics of epibulbar
      complex cartilaginous choristoma incidentally observed in a series of pterygium
      excision patients.Noncomparative case series with chart review of 8
      patients.During a 4-year period, we identified 8 cases of conventional unilateral
      nasal subpterygial cartilaginous choristoma in 1799 pterygium patients and
      analyzed their clinicopathological features. The incidence rate of this entity is
      0.44% in pterygium patients. All of the cartilaginous choristomas were buried
      deep in the caruncle, covered by the pterygium, and embedded in tenon facia
      tissue. Its clinicopathological characteristics include hyaline cartilaginous
      tissue that is surrounded by fibrous connective tissue and smooth muscle bundles.
      S-100 protein-staining specifically revealed chondrocytes embedded within
      chondroid matrix.Epibulbar complex cartilaginous choristoma covered by pterygia
      and predominantly observed in the older population is rare. The lesions were
      buried deep in the caruncle, covered by the pterygium and embedded in tenon
      fascia tissue. These findings are inconsistent with those in previous reports.

PMID- 29443764
TI  - Assessment of interchangeability rate between 2 methods of measurements: An
      example with a cardiac output comparison study.
AB  - The Bland-Altman (BA) and percentage error (PE) methods have been previously
      described to assess the agreement between 2 methods of medical or laboratory
      measurements. This type of approach raises several problems: the BA methodology
      constitutes a subjective approach to interchangeability, whereas the PE approach
      does not take into account the distribution of values over a range. We describe a
      new methodology that defines an interchangeability rate between 2 methods of
      measurement and cutoff values that determine the range of interchangeable values.
      We used a simulated data and a previously published data set to demonstrate the
      concept of the method. The interchangeability rate of 5 different cardiac output
      (CO) pulse contour techniques (Wesseling method, LiDCO, PiCCO, Hemac method, and
      Modelflow) was calculated, in comparison with the reference pulmonary artery
      thermodilution CO using our new method. In our example, Modelflow with a good
      interchangeability rate of 93% and a cutoff value of 4.8 L min, was found to be
      interchangeable with the thermodilution method for >95% of measurements.
      Modelflow had a higher interchangeability rate compared to Hemac (93% vs 86%; P =
      .022) or other monitors (Wesseling cZ = 76%, LiDCO = 73%, and PiCCO = 62%; P <
      .0001). Simulated data and reanalysis of a data set comparing 5 CO monitors
      against thermodilution CO showed that, depending on the repeatability of the
      reference method, the interchangeability rate combined with a cutoff value could
      be used to define the range of values over which interchangeability remains
      acceptable.

PMID- 29443765
TI  - Clinical significance of superior articular process as a reference point for free
      hand pedicle screw insertion in thoracic spine.
AB  - The trajectory of the pedicle screw perpendicular to the SAP (superior articular
      process) is consistent with the universal trajectory presented in the previous
      study of the entry point using computed tomography. The ideal entry point and
      trajectory of pedicle screw insertion have been a matter of considerable debate.
      We attempted to find the relationship between SAP and entry point and trajectory
      of the pedicle screw.Thoracic spine CT (computed tomography) scans of 9
      volunteers were studied. A safe zone for the trajectory of the screw in the axial
      (MarginAx) and sagittal (MarginSag) was defined as the zone between lines
      perpendicular to the SAP along the medial and lateral cortex of the pedicle in
      the axial section, and the superior and inferior cortex in the sagittal section
      without violation of the pedicle walls. The midline of MarginAx and MarginSag was
      defined as the safe entry point of the trajectory in the axial and sagittal
      planes (TrajectoryAx and TrajectorySag), respectively.MarginAx and MarginSag were
      4.14 +/- 0.99 and 9.03 +/- 2.01 mm, respectively. There was a statistically
      significant difference in TrajectoryAx between the upper and middle, and between
      the upper and lower (P = .0076 in both cases), but not between the middle and
      lower thoracic spine (P = .066). TrajectorySag was within 1 mm at the levels of
      T4, T8, T11 vertebrae and at 0 mm at the other levels. Thus, the midpoint of
      MarginSag was within 1 mm from the SAP base.There was a constant angular
      relationship with the SAP and the pedicle axis; the line perpendicular to the SAP
      can act as a trajectory. Therefore, we suggest that the SAP might be the only
      accurate and safe reference for pedicle screw insertion in the thoracic spine
      perpendicular to the SAP using freehand technique.

PMID- 29443766
TI  - Meta-analysis study comparing percutaneous coronary intervention/drug eluting
      stent versus coronary artery bypass surgery of unprotected left main coronary
      artery disease: Clinical outcomes during short-term versus long-term (> 1 year)
      follow-up.
AB  - BACKGROUND: Results on the safety and long-term efficacy of drug-eluting stent
      placement in unprotected left main coronary artery disease (ULMCAD) compared with
      those of coronary artery bypass surgery (CABG) remain inconsistent across
      randomized clinical trials and recent meta-analysis studies. We aimed to compare
      the clinical outcomes and safety over short- and long-term follow-ups by
      conducting a meta-analysis of large pooled data from randomized controlled trials
      and up-to-date observational studies. METHODS: A systematic review of PubMed,
      Google Scholar, Medline, and reference lists of related articles was performed
      for studies conducted in the drug-eluting stent era, to compare percutaneous
      coronary intervention (PCI) with CABG in ULMCAD. The primary outcome was major
      adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction
      (MI), stroke, all-cause mortality, and revascularization after at least 1-year
      follow-up. In-hospital and 30-day clinical outcomes were considered secondary
      outcomes. Furthermore, a subgroup analysis of studies with >=5 years follow-up
      was performed to test the sustainability of clinical outcomes. RESULTS: A total
      of 29 studies were extracted with 21,832 patients (10,424 in PCI vs 11,408 in
      CABG). Pooled analysis demonstrated remarkable differences in long-term follow-up
      (>=1 year) MACCE (odds ratio [OR] 1.42, 95% CI 1.27-1.59), P < .00001), repeat
      revascularization (OR 3.00, 95% CI 2.41-3.73, P < .00001), and MI (OR 1.32, 95%
      CI 1.14-1.53, P = .0002), favoring CABG over PCI. However, stroke risk was
      significantly lower in the PCI group. Subgroup analysis of studies with >=5 years
      follow-up showed similar outcomes except for the noninferiority outcome of MACCE
      in the PCI arm. However, the PCI group proved good safety profile after a minimum
      of 30-day follow-up with lower MACCE outcome. CONCLUSION: PCI for ULMCAD can be
      applied with attentiveness in carefully selected patients. MI and the need for
      revascularization remain drawbacks and areas of concern among previous studies.
      Nonetheless, it has been proven safe during short-term follow-up.

PMID- 29443767
TI  - Effect of oxycodone hydrochloride combined with flurbiprofen axetil for
      intravenous patient-controlled analgesia in lower abdominal patients: A
      randomized trial.
AB  - BACKGROUND: Problems like postoperative pain are still common phenomena after
      general anesthesia. Oxycodone hydrochloride is a semisynthetic opioid with a safe
      and excellent therapeutic effect on visceral pain. Flurbiprofen axetil has the
      efficacy of targeted analgesia. We hypothesize that different doses of oxycodone
      hydrochloride combined with flurbiprofen axetil would generate great results on
      postoperative intravenous analgesia in lower abdominal patients. METHODS: In the
      clinical trial, 90 American Society of Anesthesiologists I or II patients
      scheduled for elective general anesthesia were randomly divided into 3 groups, 30
      cases in each group. Group I: oxycodone hydrochloride 0.5 mg/kg + flurbiprofen
      axetil 150 mg, group II: oxycodone hydrochloride 0.75 mg/kg + flurbiprofen axetil
      150 mg, group III: oxycodone hydrochloride 1.0 mg/kg + flurbiprofen axetil 150
      mg. Dilute them with 0.9% saline to 150 mL, respectively, with the background
      dose of 2 mL/h, patient-controlled analgesia 2 mL per time, with an interval of
      10 min, and the loading dose of 0.1 mL/kg. Record the preoperative situation, 24
      h (T0) before surgery, postoperative situation, 1 h (T1), 4 h (T2), 8 h (T3), 12
      h (T4), 24 h (T5), 48 h (T6), 72 h (T7) after the surgery, including the mean
      arterial pressure, heart rate, saturation of pulse oximetry, static and dynamic
      pain rating (NRS) and Ramsay sedation score, effective pressing and total
      pressing ratio (referred to as the pressing ratio), patient satisfaction, and
      occurrence of adverse reactions. RESULTS: There was no significant statistic
      difference in mean arterial blood pressure, heart rate, arterial oxygen
      saturation, and adverse reactions among the 2 groups at each time point (P >
      .05). Compared with group I, the static NRS rating in group II and group III were
      significantly lower than that in group I (P < .05) from T1 to T5. The dynamic NRS
      rating of group II from T1 to T4 and that of group III from T1 to T5 were
      significantly lower (P < .05). The effective pressing and total pressing ratio
      was significantly higher (P < .05). There was no significant statistic difference
      between group II and group III in NRS rating and the effective pressing and total
      pressing ratio (P > .05). Compared with group III, the Ramsay sedation scores of
      group I and group II were significantly lower from T1 to T4 (P < .05).
      CONCLUSION: The dose of 0.75 mg/kg oxycodone hydrochloride combined with
      flurbiprofen axetil can provide safe and effective postoperative analgesia for
      lower abdominal patients, with fewer adverse reactions.

PMID- 29443769
TI  - Establishment of Comprehensive Indicators in TCM Pectoral-qi Case Report Based on
      Experts Diagnosis and Self-test Technology.
AB  - RATIONALE: To establish TCM Pectoral-qi comprehensive indicators and highlight
      the inner structure among different variables in an objective way, the article
      uses Partial Least Square Second-order Latent Variable Model (PLS-SLVM) and
      accomplishes 3 different comprehensive indicators based on both experts diagnosis
      and self-test data. SLVM includes a measurement model that defines the
      relationship between observed variables and latent variables and a structure
      model that imputes relationships between latent variables. The article focuses on
      PLS as the estimation method. Without normal distribution and independence
      assumptions, PLS uses objective weighting methods based on the data. Bootstrap
      method (B = 200) is used to calculate the mean value and standard errors of the
      PLS estimates. The article chooses the percentile interval to obtain the
      confidence interval of PLS parameters. PATIENT CONCERNS: The patients were
      diagnosed by the means of experts diagnosis and self-test technology. On the one
      hand, the patients want to know the effect of self-test by wearing a kind of
      instrument. On the other hand, we want to establish TCM Pectoral-qi comprehensive
      indicators and highlight the inner structure among different variables in an
      objective way. DIAGNOSES: The group of 59 subjects are the same no matter whether
      they were diagnosed through TCM Pectoral-qi Assessment Questionnaire of self-test
      technology. INTERVENTIONS: The same group of 59 subjects keep wearing the
      instrument for hours and get the self-test data consequently. OUTCOMES: As one of
      comprehensive indicator establishing methods, PLS-SLVM highlights the structure
      state among variables and improves the evaluation efficiency. Furthermore, it
      provides a new tool and method in TCM diseases prevention and health security.
      LESSONS: As expected, PLS-SLVM is a useful tool due to its nonassumption of
      normal distribution and independence with consideration of correlation among
      different variables. Thus PLS-SLVM can be applied in ordinal data from assessment
      questionnaire and continuous data about physicochemical indexes for the same
      group of people. It displays that PLS-SLVM builds a connection between TCM
      experts diagnosis and the self-testing technology.

PMID- 29443768
TI  - Association of human leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with
      Vogt-Koyanagi-Harada disease: A systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this study was to evaluate the association of human
      leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with Vogt-Koyanagi-Harada
      (VKH), providing further evidences on the genetic background of this disease.
      METHODS: A comprehensive literature search was conducted on the relationship of
      HLA-DQ and/or HLA-DQA1/DQB1 alleles with VKH through PubMed, Embase, Cochrane
      Library, China National Knowledge Infrastructure, VIP, and databases for grey
      literature. The last search was in October 2017. Pooled odds ratio (OR) with 95%
      confidence interval (95% CI) was calculated from extracted data to access the
      strength of the association between a genotype and VKH. RESULTS: HLA-DQ4 was
      confirmed to increase the risk of VKH significantly (OR = 4.63, 95% CI: 1.74
      12.31, P = .002), while HLA-DQ1 seemed to reduce VKH occurrence with OR = 0.32
      (95% CI: 0.22-0.47, P < .00001). HLA-DQA1*0301-(OR = 4.52, 95% CI: 1.42-14.35, P
      = .01) and HLA-DQB1*0401-(OR = 23.12, 95% CI: 11.54-46.31, P < .00001) positive
      patients probably had a rising tendency to suffer from VKH. Alleles including HLA
      DQA1*0103, 0401, 0501 and HLA-DQB1*0301, 0402, 0601, 0603 were significant
      protective genetic factors. CONCLUSION: We concluded that HLA-DQ4 carriers had a
      higher risk of VKH and HLA-DQ1 seemed to be protective. People with positive HLA
      DQA1*0301 and HLA-DQB1*0401 demonstrated to be more susceptible to VKH. HLA
      DQA1*0103, 0401, 0501 and HLA-DQB1*0301, 0402, 0601, 0603 could be potential
      protectors.

PMID- 29443770
TI  - Whether innate immune together with genetic factor are involved in leukemic
      arthritis?: A case report and review of the literature.
AB  - We report a case of leukemic arthritis (LA) of monocytic differentiation, which
      presented with spondyloarthritis-like symptoms and a positive human leukocyte
      antigen-B27, and discuss its potential mechanisms.The patient was admitted
      because of pain in her right knee and lower back for 18 months. Magnetic
      resonance imaging showed diffuse hyperintense signal in the bilateral liac bones
      and bone marrow edema and synovitis in the right knee.The diagnosis of acute
      monocytic leukemia and LA were concluded by bone marrow aspiration and flow
      cytometry of the synovial fluid.The patient had poor response to nonsteroidal
      anti-inflammatory drugs. One week after she received chemotherapy, the symptoms
      were dramatically relieved.For 5-year follow-up, she got clinical remission
      without suffering pain of the right knee and the lower back.Leukemic arthritis is
      a rare manifestation of leukemia with unknown mechanism and may be the initial
      presentation of leukemia. The problem whether abnormal immune response of the
      neoplasitc monocytes together with hereditary factors contribute to the
      pathogenesis of LA in adult is raised from this case, which worth further
      research.

PMID- 29443771
TI  - Endoscopic bronchial occlusion for postoperative persistent bronchopleural
      fistula with computed tomography fluoroscopy guidance and virtual bronchoscopic
      navigation: A case report.
AB  - RATIONALE: The development of postoperative bronchopleural fistula (BPF) remains
      a challenge in thoracic surgery. We herein report a case of BPF successfully
      treated with endoscopic bronchial occlusion under computed tomography (CT)
      fluoroscopy and virtual bronchoscopic navigation (VBN). PATIENT CONCERNS: A 63
      year-old man underwent right upper lobectomy with concomitant S6a
      subsegmentectomy for lung adenocarcinoma. On postoperative day 24, he complained
      of shaking chills with high fever. DIAGNOSES: BPF with subsequent pneumonia and
      empyema. INTERVENTIONS: Despite aggressive surgical interventions for the BPF,
      air leakage persisted postoperatively. On days 26 and 34 after the final
      operation, endobronchial occlusions were performed under CT fluoroscopy and VBN.
      OUTCOMES: The air leaks greatly decreased and the patient was discharged.
      LESSONS: CT fluoroscopy and VBN can be useful techniques for endobronchial
      occlusion in the treatment of BPF.

PMID- 29443772
TI  - Primary leiomyosarcoma in the colon: A case report.
AB  - RATIONALE: Leiomyosarcoma (LMS) is a common type of soft tissue sarcoma. Primary
      colonic LMS in general is a very rare entity, accounting for 1% to 2% of
      gastrointestinal malignancies. PATIENT CONCERNS: We report a case of 55-year-old
      female who presented with a sudden onset of sharp right lower quadrant abdominal
      pain. Electronic colonoscopy showed a normal lumen. However, an abdominal
      computed tomography scan revealed a mass of soft tissue attenuation inseparable
      from the ascending colon which appeared as a gastrointestinal stromal tumor
      (GIST). DIAGNOSES: It is important to diagnose LMS definitively by
      immunohistochemical profiling of smooth muscle actin, desmin, and CD34.
      INTERVENTIONS: She underwent laparotomy and right hemicolectomy, and histology
      confirmed a colonic LMS. The patient received no oncological treatment after
      surgery. OUTCOMES: No recurrence or metastasis was observed at 5 months
      postoperatively. It is crucial to identify colonic LMS precisely based on
      immunohistochemistry, and thereby distinguish it from GIST. LESSONS: Further
      investigation on LMS cases so far is required to establish standard treatment
      strategies.

PMID- 29443773
TI  - Anti-N-methyl-D-aspartate receptor encephalitis associated with acute Toxoplasma
      gondii infection: A case report.
AB  - RATIONALE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been
      recognized as the most frequent autoimmune encephalitis in children. Several
      infectious agents have been implicated in anti-NMDA encephalitis. PATIENT
      CONCERNS: A previously healthy immunocompetent 9-year-old girl first presented
      with seizures, headaches and vomiting. Cerebrospinal fluid and brain magnetic
      resonance imaging were normal. After one week onset, the patient gradually
      developed unexplained personality and behavior changes, accompanied by fever and
      seizures again. Repeated CSF analysis revealed a slightly lymphocytic predominant
      pleocytosis and positive anti-NMDAR antibody. A variety of pathogenic
      examinations were negative, except for positive toxoplasma IgM and IgG.
      DIAGNOSES: The patient was diagnoses for anti-NMDA encephalitis associated with
      acute acquired toxoplasma gondii infection. INTERVENTIONS: The patient received
      10 days azithromycin for treatment of acquired toxoplasma infection. The parents
      refuse immunotherapy because substantial recovery from clinical symptoms.
      OUTCOMES: The patient was substantially recovered with residual mild agitation
      after therapy for acquired toxoplasma gondii infection. Two months later, the
      patient was completely devoid of symptoms, and the levels of serum IgM and IgG of
      toxoplasma gondii were decreased. LESSONS: Acquired toxoplasma gondii infection
      may trigger anti-NMDAR encephalitis in children, which has not been reported
      previously. Clinicians should assess the possibility of toxoplasma gondii
      infection when evaluating a patient with anti-NMDA encephalitis.

PMID- 29443774
TI  - Sanders type IIIAB calcaneal fracture without broken lateral wall: A case report
      and review of literature.
AB  - RATIONALE: The calcaneal fracture without broken lateral wall is rare and the
      open anatomic reduction and internal fixation (ORIF) is necessary when the
      subtalar joint articular surface is broken and collapsed. PATIENT CONCERNS: A 45
      year-old male was admitted to our department with complaints of heel pain and
      swelling after falling down from 1-m-high stone. He was unable to bear weight on
      his right foot. DIAGNOSES: Imaging studies confirmed that it was a sanders type
      IIIAB calcaneal fracture without broken lateral wall and the middle part of the
      posterior calcaneal articular facet collapsed. INTERVENTIONS: ORIF of
      intraarticular calcaneal fracture with the locking calcaneal plate was performed.
      OUTCOMES: The patient recovered completely after 16 weeks and was able to
      participate in his usual work. LESSONS: Based on this case and literature we
      reviewed, computed tomography scan (CT scan) should be used to diagnose and
      evaluate the severity of calcaneal fractures. Currently, ORIF was the preferred
      surgical treatment option when dealing with displaced intraarticular calcaneal
      fractures.

PMID- 29443775
TI  - Primary undifferentiated pleomorphic sarcoma of the thyroid: A case report and
      review of the literature.
AB  - RATIONALE: Primary undifferentiated pleomorphic sarcoma is extremely rare in the
      thyroid, and can be easily misdiagnosed as anaplastic thyroid cancer. PATIENT
      CONCERNS: We present a case of a 71-year-old woman who presented with a rapidly
      growing painless mass in the neck. DIAGNOSES-INTERVENTIONS-OUTCOMES: Computed
      tomography showed a large hypointense mass with hyperdense areas involving whole
      of the right lobe of thyroid gland and fine-needle aspiration cytology found a
      few atypical cells. Surgical exploration was performed subsequently and frozen
      section showed malignant tumor. Therefore, a total thyroidectomy, central, and
      bilateral lateral neck dissection were performed and adjuvant radiotherapy of 60
      Gy was administered. The patient was alive and had no recurrence at 6-month
      follow-up. LESSONS: Although primary undifferentiated pleomorphic sarcoma in the
      thyroid is extremely rare, patients who presented with a rapidly growing painless
      mass in the neck should be considered and it is essential to excise the tumor
      completely as soon as possible.

PMID- 29443776
TI  - Differential expression of microRNAs in the normal skin of the Han and Uyghur
      populations in Xinjiang Province.
AB  - In this study, we investigated the expression of microRNAs (miRNAs) in the skin
      samples from the Han and Uyghur populations in Xinjiang, China. The miRNA levels
      of the normal skin samples from 10 individuals of Uyghur or Han were tested by
      microarray and the expression differentiations were compared. Among the 3100
      probes for microarray, a total of 247 miRNAs were differentially expressed in the
      Han versus Uyghur population, including 76 upregulated miRNAs and 171
      downregulated miRNAs. The most significantly upregulated miRNAs were miR-141-3p,
      miR-1915-5p, kshv-miR-K12-2-5p, and miR-222-3p. And the most significantly
      downregulated miRNAs included miR-1207-3p and miR-625-3p. We have confirmed the
      upregulation of miR-141-3p and miR-1915-5p by qRT-PCR. There were no statistical
      correlations in the expression of miR-141-3p or miR-1915-5p with the age or
      gender within each group. Interestingly, the differentially expressed miRNAs were
      enriched in some cancer-related pathways, such as p53, mitogen-activated protein
      kinase, and WNT signal pathways. Collectively, these dysregulated expressions of
      the miRNAs may provide a better understanding of the differences in the incidence
      and mortality of skin-related carcinoma between the Uyghur and Han populations in
      Xinjiang.

PMID- 29443777
TI  - Oral leukoplakia, a precancerous lesion of squamous cell carcinoma, in patients
      with long-term pegylated liposomal doxorubicin treatment.
AB  - Pegylated liposomal doxorubicin (PLD) has a good safety profile, but long-term
      use has been associated with development of squamous cell carcinoma of the tongue
      and oral cavity (SCCTO) in some patients. The study objective was to estimate the
      prevalence of oral leukoplakia, a known precursor of SCCTO, in patients with
      ovarian cancer and long-term PLD use.After approval of the institutional review
      board, medical record of 114 patients who were treated with PLD at our
      institution between January 2010 and December 2016 were retrospectively reviewed.
      All those patients have been referred for routine monitoring of oral mucositis
      every time before administration by a dentist. The patient characteristics
      included in the evaluation were age, smoking and drinking habits, the PLD dose
      and schedule, and presence or absence of oral leukoplakia and SCCTO at each oral
      examination. The relationships of the incidence of oral leukoplakia and patient
      characteristics were analyzed.The median total PLD dose was 160 (range 40-1550)
      mg/m. Oral leukoplakia was seen in 6 (5.3%) patients. The median PLD dose, at the
      time of oral leukoplakia diagnosis, was 685 (range 400-800) mg/m. SCCTO was not
      found. Univariate analysis revealed that age, Brinkman index, and habitual
      drinking were not considered as risk factors for oral leukoplakia, and only total
      PLD dose (OR, 1.470; 95% CI, 1.19-1.91; P < .001) remained as a significant
      independent risk factor for oral leukoplakia. The ROC curve analysis indicated
      that the optimal cutoff value of the total PLD dose to predict development of
      oral leukoplakia was 400 mg/m. The sensitivity was 100% and the specificity was
      88.8%. No patient discontinued PLD because of oral leukoplakia or SCCTO.The 2
      most important clinical observations were the occurrence of oral leukoplakia in
      patients with long-term PLD use and that the development of oral leukoplakia was
      related to a total cumulative dose >=400 mg/m. Routine oral surveillance is
      recommended, particularly when the cumulative total dose exceeds 400 mg/m.

PMID- 29443778
TI  - A primitive neuroectodermal tumor in an adult: Case report of a unique location
      and MRI characteristics.
AB  - RATIONALE: Central nervous system primitive neuroectodermal tumors (CNS PNETs)
      mostly occur in children and present as cerebellar medulloblastoma. A few cases
      of PNETs occur in the cerebral hemisphere. The presence of a PNET in ventricles
      is extremely rare. The prognosis of CNS PNET is extremely poor, and the 5-year
      survival rate does not exceed 35%. In the present study, we describe the first
      case of a PNET in the ventricles with good prognosis. PATIENT CONCERNS: The case
      of a 36-year-old man is reported, who presented with a progressively worsening
      headache for 2 months. DIAGNOSES: Magnetic resonance imaging (MRI) revealed
      multiple tubercula on the walls of the lateral and third ventricles.
      Histopathologic analysis revealed a hypercellular tumor with small round cells
      containing hyperchromatic nuclei and a high nucleus:cytoplasm ratio. The analysis
      was consistent with PNET. INTERVENTIONS: Radiation therapy covering the entire
      craniospinal axis was administered, with Temozolomide for synchronous auxiliary
      treatment. OUTCOMES: The patient was follow-up for a year and showed no signs of
      recurrence. LESSONS: We present the first CNS PNET located in the ventricles with
      good prognosis. In this case, radiotherapy with Temozolomide auxiliary treatment
      presented good efficacy and safety to treat PNET. Additional studies on
      biomarkers may be useful in predicting personalized therapeutic response.

PMID- 29443779
TI  - Cerebral infarction due to malposition of cervical pedicle screw: A case report.
AB  - RATIONALE: Malposition of cervical pedicle screw (CPS) has a risk of vertebral
      artery (VA) injury which sometimes may cause unexpected and catastrophic outcome.
      A rare case of delayed onset of cerebral infarction caused by malposition of CPS
      was reported. PATIENT CONCERNS: A 23-year-old man who underwent a posterior
      cervical reduction and fusion of C4-5 using CPS fixation and allograft for
      cervical spine injury is presented. The patient suffered progressively weakness
      and numbness for both of upper and lower extremities 1 day after the operation.
      Computed tomography scans revealed bilateral occupation of the pedicle screws in
      the foramen of C4 and C5 and the magnetic resonance imaging (MRI) displayed
      several areas of infarction in the brainstem and cerebellum. DIAGNOSES: Plain
      radiographs of the cervical spine revealed the C4 vertebral body and MRI
      displayed a disruption of the anterior longitudinal ligament on the level of C4-5
      and severe injury to the soft tissues of the cervical spine at admission.
      Brainstem and cerebellum infarction was diagnosed at postoperative. INTERVENTION:
      A revision surgery was decided to remove all of the pedicle screws and place
      lateral mass screws instead. OUTCOMES: The patient felt better on his all of 4
      extremities following revision surgery. Fortunately, he was neurologically close
      to normal at a 3-month follow-up. LESSONS: Delayed onset of cerebral infarction
      is rarely reported complication caused by malposition of CPS. When a CPS
      perforates the transverse foramen and causes symptom of cerebral infarction, a
      revision surgery in time is strongly recommended to prevent further sequelae.

PMID- 29443780
TI  - Analysis of the characteristics of optical coherence tomography angiography for
      retinal cavernous hemangioma: A case report.
AB  - RATIONALE: Retinal cavernous hemangioma is a rare congenital vascular
      malformation with typical fundus changes. Optical coherence tomography
      angiography (OCTA), which is in rise in the recent years, is a rapid and
      noninvasive technology to assist in obtaining information regarding the blood
      flow changes in the fundus lesions from different layers without injecting a
      contrast agent. PATIENT CONCERNS: A 40-year-old male patient with visual
      occlusion in the right eye for >1 month was reported. DIAGNOSES: Retinal
      cavernous hemangioma was diagnosed by fundus examination, fluorescein angiography
      (FA) and OCTA, and the characteristics of OCTA images were analyzed.
      INTERVENTIONS: The lesion occurred outside the macula, the central vision
      remained basically normal, and no significant complications were noted in this
      patient. Therefore, we preferred to regularly follow-up without therapeutic
      intervention. CONCLUSIONS: OCTA can display fundus blood flow and vascular
      lesions noninvasively and rapidly. On OCTA, retinal cavernous hemangiomas showed
      characteristic changes and have good correspondence with fundus imaging and FA
      examinations. Moreover, OCTA remains more sensitive to vascular abnormalities,
      and imaging remains clearer, providing new diagnosis and follow-up route for this
      disease.

PMID- 29443781
TI  - Unexpected custodial death due to acute epiglottitis: A rare autopsy case report.
AB  - RATIONALE: Acute epiglottitis is a potentially life-threaten disease, which makes
      it more challenging to save the life for doctors. Unexpected deaths in custody
      are a primary cause of concern for the forensic community and doctor worldwide.
      PATIENT CONCERNS: We present a case of a 44-year-old male detainee who was
      clinically suspected of dying of acute epiglottitis. The man experienced failure
      of resuscitation and died after admitted to a hospital. DIAGNOSES: The autopsy,
      toxicological testing, the test of immunoglobulin E and bacterial culture
      suggested the patient died of acute epiglottitis. INTERVENTIONS: The bacterial
      culture was performed to imprecisely identify the cause of death. OUTCOMES: The
      bacterial culture of the patient's heart blood and nasal and throat swabs showed
      the presence of the pathogenic microorganism Haemophilus influenza type B.
      LESSONS: We aim to provide a reference to the medical and forensic community and
      remind the local law enforcement agencies on the problems present within the
      correctional healthcare system through this case report. Additionally, we also
      aim to increase the current knowledge and understanding on custodial deaths
      caused by natural diseases.

PMID- 29443783
TI  - Giant GIST of the stomach: a successful case of safe resection with preoperative
      simulation using three-dimensional CT angiography: Case report.
AB  - RATIONALE: We report a very rare case of safely resectable giant gastrointestinal
      stromal tumor (GIST) with preoperative three-dimensional computed tomography (3D
      CT) angiography in spite of no neoadjuvant treatment. PATIENT'S CONCERN: A 71
      year-old woman presented to our hospital with an abdominal giant tumor. As this
      giant tumor could not be accurately diagnosed by preoperative investigation, we
      had to perform her surgical treatment without neoadjuvant treatment. However,
      preoperative 3D-CT angiography clearly showed that the tumor was supplied by the
      right gastroepiploic artery (RGA). Based on the preoperative information, a
      surgical procedure was undertaken. DIAGNOSIS: Giant tumor of stomach with
      suspicion of GIST. INTERVENTIONS: Laparotomy guided by 3D-CT imaging including
      angiography. OUTCOME: The giant tumor originated from the greater curvature of
      the distal stomach and was supplied by the RGA, as expected. The tumor was
      resected easily under the accurate preoperative anatomical information. The tumor
      measured 20 cm * 20 cm in size and weighed 2500 g (Fig. 2C and D).
      Histopathological examination showed evidence of growth of spindle-shaped cells
      and a low mitotic index (3 per 50 high-power field, Fig. 3B). Immunohistochemical
      examination showed positive immunoreactions for KIT, CD34, and DOG1 (Fig. 3 C-E),
      but negative ones for SMA and S-100 protein (Fig. 3F and G). Consequently, we
      made a final diagnosis of an extra luminal GIST of the stomach. The post
      operative course was uneventful, and so the patient was discharged on
      postoperative day 13. LESSONS: Making full use of an imaging procedure such as 3D
      CT angiography is one of the effective tools for the surgical management of giant
      size tumors including giant GISTs.

PMID- 29443782
TI  - Putative lung adenocarcinoma with epidermal growth factor receptor mutation
      presenting as carcinoma of unknown primary site: A case report.
AB  - RATIONALE: Only a few cases of putative lung adenocarcinoma presenting as
      carcinoma of unknown primary site (CUP) with epidermal growth factor receptor
      (EGFR) mutation have been reported, and the efficacy of EGFR-tyrosine kinase
      inhibitors (TKIs) for these cases is unclear. PATIENT CONCERNS AND DIAGNOSES: A
      67-year-old man complained of paresis of the right lower extremity, dysarthria,
      and memory disturbance. Computed tomography and magnetic resonance imaging showed
      multiple brain tumors with brain edema and swelling of the left supraclavicular,
      mediastinal, and upper abdominal lymph nodes. Moreover, a metastatic duodenal
      tumor was detected via upper gastrointestinal endoscopy examination. The biopsy
      specimen of the lesion was examined and was diagnosed as adenocarcinoma with CK7
      and TTF-1 positivity. Finally, the case was diagnosed as EGFR mutation-positive
      putative lung adenocarcinoma presenting as CUP. INTERVENTIONS AND OUTCOMES: Oral
      erlotinib, an EGFR-TKI, was administered at 150 mg daily. Five weeks later, the
      brain lesions and several swollen lymph nodes showed marked improvement, and the
      symptoms of the patient also improved. Three months later, the duodenal lesion
      was undetected on upper gastrointestinal endoscopy. After an 8-month follow-up,
      the patient was well with no disease progression. LESSONS: Putative lung
      adenocarcinoma presenting as CUP may have EGFR mutation, and EGFR-TKI therapy may
      be effective for such malignancy.

PMID- 29443784
TI  - A thyroid storm patient with protracted disturbance of consciousness and
      reversible lesion in the splenium of corpus callosum: A case report.
AB  - RATIONALE: Various neurological manifestations are observed in thyroid storm
      patients but protracted disturbance of consciousness is rare. PATIENT CONCERNS: A
      58-year-old male was admitted to our hospital after a traffic accident.
      DIAGNOSES: Although awake on arrival, he fell into coma after admission. Based on
      the clinical symptoms and hyperthyroidism, the patient was diagnosed with thyroid
      storm (TS). INTERVENTIONS: Even after improvement of hyperthyroidism, disturbance
      of consciousness was protracted. Considering the possibility of immune-related
      etiology, methylprednisolone pulse was started. OUTCOMES: His consciousness level
      improved over a 3-month period, and he became able to walk with some assistance
      after 6 months. LESSONS: His condition was atypical of TS-associated
      encephalopathy because of the long clinical course. Reversible splenial lesion
      was visible using brain imaging. In some cases of TS, disturbance of
      consciousness can be protracted for several months, but it is reversible.
      Therefore, it is necessary to judge the long-term neurological outcome carefully.

PMID- 29443785
TI  - Can endotracheal intubation be the first step in management of nonconvulsive
      status epilepticus?: A case report.
AB  - RATIONALE: Nonconvulsive status epilepticus (NCSE) is prolonged seizure activity
      without motor manifestations. Clinically, there are certain examination findings,
      in addition to elements of history, that help differentiate it from other
      encephalopathies. When diagnosing NCSE, the physician faces significant
      difficulties due to inconsistent clinical presentation and somewhat nonspecific
      electroencephalogram (EEG) criteria. PATIENT CONCERNS: To highlight the problems
      faced when dealing with such a patient, a case of a 29-year-old male who
      presented with an altered state of consciousness is put forth for the reader.
      Only after an extensive laboratory and radiological workup had ruled out other
      causes, an eventual diagnosis was established when clinical features were
      correlated with suggestive EEG results. DIAGNOSES: The diagnosis that was reached
      was NCSE. INTERVENTIONS: The initial therapeutic interventions generally deployed
      in such a scenario ultimately failed and consequently the patient had to be
      sedated and intubated, while being kept on antiepileptic medication. OUTCOMES:
      This measure resulted in satisfactory recovery. LESSONS: Accordingly, we
      recommend consideration of NCSE in any unconscious patient whose presentation
      cannot be explained by other disorders. Furthermore, we suggest moving directly
      to utilizing anesthetic agents and endotracheal intubation, together with anti
      epileptic drugs, in the treatment regimen in order to optimize patient outcomes.

PMID- 29443786
TI  - Improved vacuum sealing drainage for treatment of surgical site infection
      following posterior spinal internal fixation: A case report.
AB  - RATIONALE: Surgical site infection (SSI) following spine surgeries involving
      internal fixation often require removing the instrument; however, this can cause
      spinal instability. Previous reports have demonstrated the usefulness of vacuum
      sealing drainage (VSD) therapy, but the cases require wound opening, aseptic
      condition to replace the VSD device, and a secondary operation to close the
      wound. Thus, to improve the VSD treatment and develop a maneuverable procedure,
      make sense in spine surgery. PATIENTS CONCERNS: A 59-year-old male patient with a
      T12 vertebral fracture was affected by SSIs after spinal osteotomy with internal
      fixation. DIAGNOSES: The patient complained of wound exudation and had a fever 3
      weeks after posterior spinal surgery. Initial serum investigations showed
      elevated white blood cell count and bacterial cultures of wound exudate were
      positive for Enterococcus faecalis. Therefore, SSI is confirmed. INTERVENTIONS:
      The infection was not controlled after 2 debridements, so the patient was treated
      with VSD treatment. The VSD foam dressings containing a drainage tube were placed
      into the wound from the exudation site of the wound until they contacted the
      internal fixation devices. After covering external fixation devices, continuous
      drainage was performed for 24 h. The VSD device was replaced every 4 to 5 days
      until the wound effusion stopped. All of the operations were performed at the
      bedside without complex manipulation or secondary closure under harsh aseptic
      condition. OUTCOMES: Wound exudation decreased remarkably and the infection was
      controlled 2 weeks after the application of VSD treatment. After 5 weeks,
      inflammatory indicators all decreased to normal levels and the exudate of the
      wound had stopped. The VSD treatment was then terminated and the drainage site of
      the wound was sutured. After 7 weeks, complete wound healing was achieved and no
      infection recurred during the 6-month follow-up. LESSONS: VSD could be a reliable
      treatment for SSIs that require preservation of internal fixation. Complete
      opening of the wound during the VSD treatment and secondary wound closure surgery
      were avoided.

PMID- 29443787
TI  - Spontaneous cerebrospinal fluid rhinorrhea: A case report and analysis: Erratum.

PMID- 29443788
TI  - A prospective, randomized, open label, controlled study investigating the
      efficiency and safety of 3 different methods of rectus sheath block analgesia
      following midline laparotomy.
AB  - BACKGROUND: There is a controversy regarding the efficacy of rectus sheath block
      (RSB). The aim of the present study was to evaluate analgesic efficacy and safety
      of three different methods of RSB in postoperative pain management after midline
      laparotomy. METHODS: A prospective, randomized, controlled, open-label clinical
      trial with 4 parallel groups was conducted in a tertiary care hospital in
      Finland. A total of 57 patients undergoing midline laparotomy were randomized to
      the control group (n = 12) or to 1 of the 3 active RSB analgesia groups: single
      dose (n = 16), repeated-doses (n = 12), or continuous infusion (n = 17). Opioid
      consumption with iv-patient-controlled analgesia pump was recorded, and pain
      scores and patients' satisfaction were surveyed on an 11-point numeric rating
      scale for the first 48 postoperative h. Plasma concentrations of oxycodone and
      levobupivacaine were analyzed. All adverse events during the hospital stay were
      recorded. RESULTS: Oxycodone consumption was less during the first 12 h in the
      repeated-doses and in the continuous infusion groups (P = .07) and in numerical
      values up to 48 h in the repeated-doses group. Plasma oxycodone concentrations
      were similar in all 4 groups. Pain scores were lower in the repeated-doses group
      when coughing during the first 4 h (P = .048 vs. control group), and at rest on
      the first postoperative morning (P = .034 vs. the other 3 groups) and at 24 h (P
      = .006 vs. the single-dose group). All plasma concentrations of levobupivacaine
      were safe. The patients' satisfaction was better in the repeated-doses group
      compared with the control group (P = .025). No serious or unexpected adverse
      events were reported. CONCLUSIONS: RSB analgesia with repeated-doses seems to
      have opioid sparing efficacy, and it may enhance pain relief and patients'
      satisfaction after midline laparotomy.

PMID- 29443789
TI  - Polymorphisms of drug-metabolizing enzyme CYP2E1 in Chinese Uygur population.
AB  - Pharmacogenetics is the genetic basis of pharmacokinetics, genetic testing, and
      clinical management in diseases. Evaluation about genetic alterations of drug
      metabolizing enzymes in human genome contributes toward understanding the
      interindividual and interethnic variability for clinical response to potential
      toxicants. CYP2E1 gene encodes a drug-metabolizing enzyme that metabolizes mostly
      small, polar molecules, including toxic laboratory chemicals. The aim of this
      study was to investigate CYP2E1 polymorphisms and gene profile in a Chinese Uygur
      population. Frequencies for the CYP2E1 mutated alleles and genotypes were
      screened in 100 unrelated random healthy Uygur volunteers. PCR and direct
      sequencing revealed a total of 32 polymorphisms, of which 5 novel mutations were
      presented. Rs 943975 was the most common single nucleotide polymorphism (SNP).
      The allele frequencies of CYP2E11A, 4, 7A, and 7C were 65.5, 2, 19.5, and 13%,
      respectively. The most common genotype combinations were CYP2C191A/1A (43%) and
      1A/7C (24%). Functional prediction for 2 nonsynonymous mutations G173S and V179I
      was performed using MutationTaster, sorting intolerant from tolerant, and
      PolyPhen-2. The observations of the present study give rise to useful information
      on CYP2E1 polymorphisms in Chinese Uygur individuals. The results suggest
      important clinical implications for the use of medications metabolized by CYP2E1
      among Uygurs.

PMID- 29443790
TI  - Rotational atherectomy ablation for an unexpandable stent under the guide of
      IVUS: A case report.
AB  - RATIONALE: Inadequate stent expansion due to rigid calcified may result in
      restenosis lesions, but the available options are limited. PATIENT CONCERNS: We
      report a case via the trans-radial approach of the severely underexpanded freshly
      deployed stent due to heavily calcified plaques DIAGNOSES:: Coronary angiography
      revealed that there was no adequate expansion of the freshly deployed stent.
      INTERVENTIONS: Under the guide of intravascular ultrasound (IVUS), rotational
      atherectomy (RA) successfully ablated the stent layers and the protruding
      calcified plaque. Followed by balloon angioplasty, the ablated segment was
      scaffolded with another stent, well expanded and documented by IVUS. OUTCOMES:
      The patient was uneventful during the procedure and remained angina free at the
      point of one year of clinical follow-up. LESSONS: This case indicated that RA via
      the trans-radial approach could be a useful remedy in the situation of under
      expansion of implanted stents, and the debulking should be performed under IVUS
      guidance.

PMID- 29443791
TI  - Direction-changeable lumbar cage versus traditional lumbar cage for treating
      lumbar spondylolisthesis: A retrospective study.
AB  - Despite the diverse designs for the lumbar interbody fusion cage, there is no
      consensus on the optimal design to date. The current study aimed to compare the
      efficacy and complications associated with the direction-changeable and
      traditional lumbar cages for treating lumbar spondylolisthesis.We conducted a
      retrospective study including 109 patients with lumbar spondylolisthesis, who
      were admitted to our hospital from January 2013 to December 2014. The patients
      were divided into the direction-changeable (group A) and traditional (group B)
      lumbar cage group.All patients underwent single-level transforaminal lumbar
      interbody fusion and were followed up for 12 to 24 months. There were 52 cases in
      group A and 57 cases in group B. Surgery-related parameters, including operation
      time, bleeding volume, and hospitalization time, were recorded; there was no
      significant difference between the 2 groups regarding these parameters. The
      visual analog scale and Oswestry disability index at the last follow-up showed
      significant improvement compared with preoperative values in both groups (P <
      .05). Patients in group A demonstrated more intervertebral space height
      maintenance postoperatively than patients in group B but the difference was not
      statistically significant (P > .05). In group A, complications included 3 cases
      of nonunion (5.77%) and 1 case of cerebrospinal fluid leakage (1.92%). In group
      B, complications included 9 cases of nonunion (15.79%) and 1 case of
      postoperative infection (1.75%). There was a significant difference between both
      groups in terms of the nonunion rate and total complication rate (P < .05).The
      direction-changeable lumbar cage has merits such as a higher bone fusion rate and
      fewer postoperative complications compared to the traditional lumbar cage.

PMID- 29443792
TI  - Pleural cavity cytokine release syndrome in CD19-directed chimeric antigen
      receptor-modified T cell therapy: A case report.
AB  - RATIONALE: Cytokine release syndrome (CRS) is a common and potentially fatal
      complication of CAR-T cell therapy. However, compartment CRS is relatively rare
      in hematological malignancies, as well as in solid tumors. The pathogenesis and
      prognosis of compartment CRS are unclear and there is no standardized treatment
      yet. In this case report, we will introduce a patient developing pleural cavity
      CRS after CART19s infusion. PATIENT CONCERNS: A 28-year-old woman was admitted
      for evaluation of mediastinal mass. Her relevant examinations were comoleted.
      DIAGNOSES: She was diagnosed as diffuse large B cell lymphoma (DLBCL, non-GCB
      type). INTERVENTIONS: She received chemotherapies including 1 cycle of R
      DAEPORCH, 1 cycle of R-CHOPE, 2 cycles of R-CHOP, and 4 cycles of R-GDP during
      the disease course. OUTCOMES: The cytokine levels of hydrothorax were
      considerably high when serum cytokines were within normal range, with IL-6 at
      1212.45 versus 5.69 pg/mL. qPCR analysis for CAR constructs showed 1,119,696
      copies/MUg DNA in hydrothorax and 522,227 copies/MUg DNA in blood. LESSONS: The
      results indicated that CART19 cells trafficked to the pleural cavity and
      interacted with the CD19-positive lymphoma cells directly, causing cytokine
      release in situ.

PMID- 29443793
TI  - Olanzapine-induced peripheral eosinophilia and eosinophilic pleural effusion: A
      case report.
AB  - RATIONALE: Eosinophilic pleural effusion (EPE) is an eosinophil count >=10% in
      pleural effusion, which is a rare condition in drug therapy. PATIENT CONCERNS: We
      describe the case of a 70-year-old Alzheimer patient who was taking olanzapine
      for 2 months for the treatment of depression, and developed peripheral
      eosinophilia and bilateral EPE. DIAGNOSES: Olanzapine-induced peripheral
      eosinophilia and eosinophilic pleural effusion was diagnosed. INTERVENTIONS:
      Olanzapine was discontinued, and repeated drainage of fluid from the pleural
      cavity was performed. OUTCOMES: All symptoms-as well as the EPE-were resolved 6
      months later. LESSONS: This case is a reminder that olanzapine may be a potential
      agent for EPE, and that this should be considered in clinical practice.

PMID- 29443794
TI  - Stability of Early EEG Background Patterns After Pediatric Cardiac Arrest.
AB  - PURPOSE: We aimed to determine whether EEG background characteristics remain
      stable across discrete time periods during the acute period after resuscitation
      from pediatric cardiac arrest. METHODS: Children resuscitated from cardiac arrest
      underwent continuous conventional EEG monitoring. The EEG was scored in 12-hour
      epochs for up to 72 hours after return of circulation by an
      electroencephalographer using a Background Category with 4 levels (normal, slow
      disorganized, discontinuous/burst-suppression, or attenuated-featureless) or 2
      levels (normal/slow-disorganized or discontinuous/burst-suppression/attenuated
      featureless). Survival analyses and mixed-effects ordinal logistic regression
      models evaluated whether the EEG remained stable across epochs. RESULTS: EEG
      monitoring was performed in 89 consecutive children. When EEG was assessed as the
      4-level Background Category, 30% of subjects changed category over time. Based on
      initial Background Category, one quarter of the subjects changed EEG category by
      24 hours if the initial EEG was attenuated-featureless, by 36 hours if the
      initial EEG was discontinuous or burst-suppression, by 48 hours if the initial
      EEG was slow-disorganized, and never if the initial EEG was normal. However,
      regression modeling for the 4-level Background Category indicated that the EEG
      did not change over time (odds ratio = 1.06, 95% confidence interval = 0.96-1.17,
      P = 0.26). Similarly, when EEG was assessed as the 2-level Background Category,
      8% of subjects changed EEG category over time. However, regression modeling for
      the 2-level category indicated that the EEG did not change over time (odds ratio
      = 1.02, 95% confidence interval = 0.91-1.13, P = 0.75). CONCLUSIONS: The EEG
      Background Category changes over time whether analyzed as 4 levels (30% of
      subjects) or 2 levels (8% of subjects), although regression analyses indicated
      that no significant changes occurred over time for the full cohort. These data
      indicate that the Background Category is often stable during the acute 72 hours
      after pediatric cardiac arrest and thus may be a useful EEG assessment metric in
      future studies, but that some subjects do have EEG changes over time and
      therefore serial EEG assessments may be informative.

PMID- 29443795
TI  - POSTERIOR PRECORTICAL VITREOUS POCKETS IN HIGH MYOPIA OBSERVED BY ENHANCED
      VITREOUS IMAGING OF SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.
AB  - PURPOSE: To observe the vitreous in highly myopic eyes with posterior precortical
      vitreous pockets (PPVPs) using enhanced vitreous imaging of spectral domain
      optical coherence tomography. METHODS: Fifty-two highly myopic eyes with PPVPs of
      36 patients were included in this study. All subjects underwent enhanced vitreous
      imaging optical coherence tomography. The size of PPVPs was measured, and the
      frequency of imaging features was recorded. RESULTS: Nine imaging features of the
      vitreous in highly myopic eyes with PPVPs were found. The average age of subjects
      was 38.1 +/- 10.8 years. The mean height of PPVPs was 1,177 +/- 704 MUm, and the
      mean width was 7,440 +/- 755 MUm. Hyperreflective line and the interlayer were
      observed in 30 (57.7%) eyes. Hyperreflective dots were found in 37 (71.2%) eyes.
      More central vitreous space was more frequently detected in younger patients.
      Prevascular vitreous fissure was detected in 7 (13.5%) eyes. W-shaped cavity,
      identified as an empty space with a smooth W-shaped edge, was demonstrated to be
      the fusion of Cloquet's canal and the extension of PPVPs. Perpendicular
      hyperreflective parallel strands were detected in 3 (5.8%) eyes. Hyperreflective
      network was observed in 10 (19.2%) eyes. Hyperreflective parapapillary tubercle
      was found in 7 (13.5%) eyes. CONCLUSION: Nine imaging features of the vitreous in
      highly myopic eyes with PPVPs were visualized by enhanced vitreous imaging
      optical coherence tomography.

PMID- 29443796
TI  - Correspondence.

PMID- 29443797
TI  - OUTCOME OF ENDOVASCULAR PROCEDURES ON OCULAR FINDINGS IN TAKAYASU ARTERITIS.
AB  - PURPOSE: To evaluate the outcome of endovascular procedures on ocular findings in
      patients with Takayasu arteritis. METHODS: Retrospective study of patients who
      underwent percutaneous endovascular stenting of aortic arch arteries for Takayasu
      arteritis (TA) and who had documented retinopathy findings before and after the
      procedure. Change in visual acuity, regression of retinopathy, and development of
      complications after endovascular procedure were studied over a follow-up of 6
      months. RESULTS: Ten eyes of five patients were included. Eyes which had Stage II
      or less of retinopathy before the endovascular procedure had favorable outcome;
      however, those with advanced stage of retinopathy at presentation had poor
      outcomes. Patients who underwent revascularization of both-sided arteries within
      1 month had better anatomical and functional outcomes as compared with those who
      underwent sequential endovascular procedures on their arteries after a gap of 3
      months or more. CONCLUSION: Percutaneous endovascular stenting of aortic arch
      arteries, affected in TA, can lead to reversal of retinopathy changes and
      restoration of vision if done before neovascular complications set in.

PMID- 29443798
TI  - CLINICAL FEATURES, IMAGING, AND NATURAL HISTORY OF MYELINATED RETINAL NERVE FIBER
      LAYER.
AB  - PURPOSE: To evaluate the natural history of myelinated retinal nerve fiber layer
      (MRNFL) through clinical features and enhanced depth imaging optical coherence
      tomography. METHODS: This is a retrospective, noncomparative, case series of
      patients who underwent thorough clinical examination to document associated
      ocular and systemic features. Enhanced depth imaging optical coherence tomography
      was performed when MRNFL was located posteriorly and accessible to imaging.
      RESULTS: Seventy-two eyes of 62 patients had a total of 86 MRNFL lesions.
      Enhanced depth imaging optical coherence tomography (n = 42 eyes) showed that all
      lesions originated in the nerve fiber layer with preservation of the vascular
      structures. Mean thickness by enhanced depth imaging optical coherence tomography
      was 255 MUm (median, 182 MUm; range, 61-717 MUm). Natural history was obtainable
      in 58 lesions with a mean follow-up duration of 57 months (median, 37 months;
      range, 2-253 months) with no significant change overall in largest basal diameter
      (2.5 vs. 2.5 mm; P = 0.361) or thickness (255 vs. 240 MUm; P = 0.053). However,
      evidence of lesion change included growth in base only (>=0.5 mm) (3 of 58; 5%),
      growth in base (>=0.5 mm) and thickness (>=50 MUm) (3 of 58; 5%), and reduction
      in base (>=0.5 mm) after plaque radiotherapy for choroidal melanoma (3 of 58;
      5%). CONCLUSION: In general, MRNFL is a rare, benign retinal finding with a
      potential for growth in 10% of cases. This supports previous histopathological
      reports that MRNFL represents accumulation of both myelin and oligodendrocytes
      and could be an oligodendrocytic choristoma.

PMID- 29443799
TI  - A SIMPLE, INEXPENSIVE LASSO FOR INTRAOCULAR FOREIGN BODY EXTRACTION.

PMID- 29443800
TI  - Correspondence.

PMID- 29443802
TI  - FULL-THICKNESS MACULAR HOLE WITH MACULAR INTRACHOROIDAL CAVITATION IN A PATIENT
      WITH PATHOLOGIC MYOPIA.
AB  - PURPOSE: To describe a full-thickness macular hole (MH) opening to macular
      intrachoroidal cavitation in a patient with pathologic myopia. METHODS: Full
      ophthalmologic examination, fundus camera (Topcon TRC; Topcon Co, Tokyo, Japan),
      optical coherence tomography (RetinaScan Advanced RS-3000; NIDEK, Gamagori,
      Japan) imaging, and cataract surgery. RESULTS: A 61-year-old woman admitted with
      decreased vision in the left eye. Visual acuity was counting fingers from 30 cm.
      Anterior segment examination showed advanced cataract. Fundus examination
      revealed pathologic myopia. There was full-thickness MH opening to macular
      intrachoroidal cavitation in contact with the anterior surface of the sclera
      subfoveally. Except for the communicating part of MH and macular intrachoroidal
      cavitation, outer retina, ellipsoid zone, and retinal pigment epithelium were
      intact. Choroid was intact except for a small part at subfoveal area. The patient
      received an uncomplicated cataract surgery. Visual acuity improved to 5/10.
      Because she was satisfied, MH surgery was postponed to a later date. CONCLUSION:
      Full-thickness MH may occur within the area of macular intrachoroidal cavitation
      in pathologic myopia.

PMID- 29443801
TI  - Reply.

PMID- 29443803
TI  - NEWLY DIAGNOSED ASYMPTOMATIC RETINAL ASTROCYTIC HAMARTOMA IN AN OLDER ADULT.
AB  - BACKGROUND: To report a coincidentally discovered retinal astrocytic hamartoma in
      an asymptomatic older woman with no history of tuberous sclerosis or
      neurofibromatosis. METHODS: A 63-year-old Turkish woman underwent routine
      ophthalmic examination. RESULTS: Visual acuity was 20/25 in each eye. On fundus
      examination, the right eye showed a flat yellow-white superficial retinal lesion
      in the inferotemporal macula and measuring 1 mm in diameter. The lesion was
      unmeasurable using B-mode ultrasonography. Spectral domain optical coherence
      tomography revealed the mass with thickening in the retinal nerve fiber layer,
      with minor disorganization of the underlying retina and no retinal or
      vitreoretinal traction. Fluorescein angiography disclosed the mass as early
      isofluorescence with late mild hyperfluorescence, without leakage. Findings in
      the left eye were normal. Based on the clinical and imaging results, a diagnosis
      of noncalcified small retinal astrocytic hamartoma was rendered. The lesion
      remained unchanged at 1-year follow-up. CONCLUSION: Small coincidentally
      discovered retinal astrocytic hamartomas in older patients can be difficult to
      diagnose and possibly cause diagnostic confusion with other conditions including
      myelinated nerve fiber and cotton wool spot. Retinal astrocytic hamartoma is
      characterized by thickening of the retinal nerve fiber layer and mild compression
      and disorganization of the underlying retinal layers on spectral domain optical
      coherence tomography.

PMID- 29443804
TI  - PROGRESSION OF RETINAL ISCHEMIA IN A CASE OF MACULAR TELANGIECTASIA TYPE 1 AFTER
      RANIBIZUMAB INJECTION: OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS.
AB  - PURPOSE: To describe a case of a 68-year-old man with macular telangiectasia
      (MacTel) Type 1 in the right eye, showing an increase in capillary ischemia after
      intravitreal ranibizumab. METHODS: The patient underwent complete ophthalmologic
      evaluation, including best-corrected visual acuity, intraocular pressure,
      anterior segment and fundus examination, optical coherence tomography (OCT), and
      OCT angiography at baseline and on each visit. Fluorescein angiography was
      performed at baseline. The patient was followed up on monthly bases for 22
      months. RESULTS: The patient presented a best-corrected visual acuity of 20/80 in
      the right eye and of 20/25 in the left eye at baseline. In the right eye, the
      fluorescein angiography images showed perifoveal capillary ectasia, late-frames
      dye leakage, and enlargement of the foveal avascular zone. The OCT showed
      intraretinal pseudocysts and microaneurysms, and the OCT angiography showed
      vascular rarefaction, capillary dropout, and capillary ectasia of the superficial
      plexus. After 16 months of follow-up and four ranibizumab injections, the best
      corrected visual acuity was 20/60, and the OCT angiography disclosed a further
      enlargement of the foveal avascular zone area and increased capillary
      obliteration in the perifoveal nasal area. CONCLUSION: Optical coherence
      tomography angiography may represent an indispensable diagnostic technique,
      complementary to traditional imaging, in the evaluation of the effects of anti
      vascular endothelial growth factor therapy in patients with MacTel Type 1.

PMID- 29443805
TI  - NITINOL FLEX LOOP-ASSISTED RETRIEVAL AND SUTURELESS INTRASCLERAL REFIXATION OF A
      DISLOCATED INTRAOCULAR LENS IMPLANT.
AB  - BACKGROUND/PURPOSE: To describe a novel use of the flexible nitinol loop membrane
      scraper (FINESSE Flex loop; Alcon, Fort Worth, TX) for rescue and refixation of a
      dislocated intraocular lens (IOL). METHODS: A 27-gauge nitinol flex loop was used
      to lasso each haptic of a dislocated 3-piece IOL. By retracting the loop, the
      haptic could be effectively locked to the instrument and externalized through a
      scleral tunnel, thereby fixating it to the sclera in a sutureless fashion.
      RESULTS: A 50-year-old man presented with a posteriorly dislocated Sensar AR40e
      IOL (Abbott Medical Optics, Inc; Santa Barbara, CA) and retained lens material
      after a complicated cataract surgery in the left eye. His visual acuity was
      counting fingers at face. The patient underwent 27-gauge pars plana vitrectomy
      with successful rescue and refixation of the IOL using the nitinol flex loop. One
      week postoperatively, his visual acuity had improved to 20/40. CONCLUSION: The
      nitinol flex loop may be used to lasso the haptics of a dislocated IOL and
      refixate it using a sutureless intrascleral fixation technique. This instrument
      may be a safer alternative compared with forceps for retrieving posteriorly
      dislocated IOLs that are sitting on the retinal surface.

PMID- 29443806
TI  - HAND-HELD OPTICAL COHERENCE TOMOGRAPHY MONITORING OF CHEMORESISTANT
      RETINOBLASTOMA.
AB  - PURPOSE: Retinoblastoma (Rb) is a potentially fatal intraocular malignancy in
      children, and hand-held optical coherence tomography (HH-OCT) can assist in
      submillimeter detection and monitoring after treatment of Rb. Retinoblastoma
      located in the macula, or those with chemoresistance, can be among the most
      difficult to manage. We describe HH-OCT features in a case of chemoresistant
      macular Rb that eventually responded to plaque radiotherapy after failing
      intravenous chemotherapy and intraarterial chemotherapy. METHODS: Observational
      case report. RESULTS: A 15-month-old girl with leukocoria was found to have Group
      D Rb in the right eye of 6-mm thickness and macular Group B Rb in the left eye of
      4-mm thickness. She was treated with 6-monthly cycles of systemic intravenous
      chemotherapy and focal consolidation therapies to both eyes, with tumor
      regression in both eyes. However, macular tumor in the left eye demonstrated
      subsequent recurrence, from regressed thickness of 792 MUm on HH-OCT to a dome
      shaped hyperreflective retinal mass of >2000 MUm thickness. Three cycles of
      intraarterial chemotherapy were sufficient for tumor regression down to 977 MUm
      thickness on HH-OCT. Six months later, macular tumor in the left eye recurred
      again to >2000 MUm thickness and necessitated plaque radiotherapy using apex dose
      of 35 Gy over 95.25 hours. Hand-held OCT confirmed rapid tumor regression to 722
      MUm after plaque treatment and regression remained stable at 6-month follow-up.
      CONCLUSION: Hand-held OCT was critical in assessment of Rb after failed
      intravenous chemotherapy and intraarterial chemotherapy and later documenting
      regression after plaque radiotherapy. Hand-held OCT is vital in providing cross
      sectional imaging and measurements of small macular and paramacular Rbs.

PMID- 29443807
TI  - MULTIMODAL IMAGING OF ANGIOID STREAKS ASSOCIATED WITH TURNER SYNDROME.
AB  - PURPOSE: To report multimodal imaging in a novel case of angioid streaks in a
      patient with Turner syndrome with 10-year follow-up. METHODS: Case report of a
      patient with Turner syndrome and angioid streaks followed at Bellevue Hospital
      Eye Clinic from 2007 to 2017. Fundus photography, fluorescein angiography, and
      optical coherence tomography angiography were obtained. RESULTS: Angioid streaks
      with choroidal neovascularization were noted in this patient with Turner syndrome
      without other systemic conditions previously correlated with angioid streaks.
      CONCLUSION: We report a case of angioid streaks with choroidal neovascularization
      in a patient with Turner syndrome. We demonstrate that angioid streaks,
      previously associated with pseudoxanthoma elasticum, Ehlers-Danlos syndrome,
      Paget disease of bone, and hemoglobinopathies, may also be associated with Turner
      syndrome, and may continue to develop choroidal neovascularization, suggesting
      the need for careful ophthalmic examination in these patients.

PMID- 29443808
TI  - RETINAL MICROVASCULATURE ALTERATION IN PARACENTRAL ACUTE MIDDLE MACULOPATHY AND
      ACUTE MACULAR NEURORETINOPATHY: A QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY
      ANGIOGRAPHY STUDY.
AB  - PURPOSE: To present a series of idiopathic paracentral acute middle maculopathy
      (PAMM) and acute macular neuroretinopathy (AMN) cases and to compare the
      microvascular retinal status of PAMM/AMN eyes with those of healthy individuals.
      METHODS: Six eyes with PAMM and two eyes with AMN in a total of six patients were
      included in this study. Multimodal retinal imaging, including optical coherence
      tomography angiography, was performed in all patients. The vessel density of the
      superficial capillary plexus and deep capillary plexus, as well as the area,
      circularity, and angle of the superficial foveal avascular zone (FAZ) were
      measured and compared with the same parameters in age-matched healthy
      individuals. RESULTS: The optical coherence tomography angiography showed a
      decreased vessel density of both superficial capillary plexus and deep capillary
      plexus in PAMM/AMN eyes versus control eyes (12.2 +/- 0.74 vs. 14.0 +/- 1.62 mm
      [P = 0.01] in superficial capillary plexus and 18.5 +/- 1.2 vs. 20.2 +/- 1.0 mm
      [P = 0.02] in deep capillary plexus). There was no statistically significant
      change in the FAZ area between PAMM/AMN and healthy eyes. However, FAZ
      circularity in PAMM/AMN eyes was statistically significantly lower compared with
      healthy eyes (0.64 +/- 0.09 and 0.77 +/- 0.07, respectively; P = 0.01). The angle
      of FAZ was statistically significantly higher in PAMM/AMN eyes compared with
      healthy eyes (27.6 +/- 16.2 and 11.2 +/- 5.5 degrees , respectively; P = 0.005).
      CONCLUSION: Paracentral acute middle maculopathy and AMN eyes demonstrated not
      only an isolated alteration of deep retinal circulation but also general
      nonspecific changes in retinal microvasculature, including a decrease in the
      vessel density of the superficial capillary plexus and distortion of the FAZ.

PMID- 29443810
TI  - End-of-Course Examinations: 10 Tips for Preparing Your Tests.

PMID- 29443809
TI  - Association Between Visual Acuity and the Corneal Area Occupied by Granular
      Lesions, Linear Lesions, or Diffuse Haze in Patients With Granular Corneal
      Dystrophy Type 2.
AB  - PURPOSE: In granular corneal dystrophy type 2 (GCD2), corneal deposits containing
      fragments of transforming growth factor-beta-induced protein appear in sequence
      as granular lesions (GLs), linear lesions (LLs), and diffuse haze (DH). We aimed
      to investigate the association between visual acuity and age-related changes in
      lesion types in patients with GCD2. METHODS: We retrospectively evaluated the
      medical records and slit-lamp photographs of 533 patients (1066 eyes) with
      genetically confirmed GCD2 (heterozygous). Deposits were classified into GLs,
      LLs, and DH, after which the area occupied by each lesion type was measured. The
      associations between visual acuity and each lesion area were also evaluated using
      univariable and multivariable models. RESULTS: The area occupied by GLs increased
      beginning in the teen years, whereas the area occupied by DH began to increase
      after age 40. However, the area occupied by LLs increased until patients had
      reached their 40s, after which no further increases occurred. Multivariable
      analyses revealed no association between GLs and low visual acuity after
      adjusting for age and sex. Increases in the LL area were associated with lower
      odds for low visual acuity (adjusted odds ratio = 0.4 for the third tertile, 95%
      confidence interval, 0.2-0.97), whereas increases in the DH area were positively
      associated with low visual acuity (adjusted odds ratio = 3.3 for the third
      tertile of the DH area, 95% confidence interval, 1.3-8.3). CONCLUSIONS: Our
      findings indicated that LLs associated with GCD2 do not produce significant
      decreases in visual acuity, whereas DH exerts the most significant negative
      impact on visual acuity. Late-onset DH may be associated with the termination of
      LL formation.

PMID- 29443811
TI  - Teaching Nursing Students, Nurses, and Other Health Care Providers About Ethics
      Consultations.

PMID- 29443812
TI  - A Tool to Guide Students in Identifying Problem Concepts, Assessment, and
      Diagnosis.

PMID- 29443813
TI  - Writing Letters (to Oneself): Strategy to Reflect on Clinical Practice.

PMID- 29443815
TI  - Teaching Vaginal Hysterectomy via Simulation: Creation and Validation of the
      Objective Skills Assessment Tool for Simulated Vaginal Hysterectomy on a Task
      Trainer and Performance Among Different Levels of Trainees.
AB  - OBJECTIVES: The use of simulation-based education to train surgeons is widely
      accepted. Although many authors describe the use of an Objective Skills
      Assessment Test (OSAT) to assess performance of various surgical procedures,
      there is a paucity of research on use of this modality to evaluate vaginal
      surgery skills. We created a vaginal hysterectomy procedure-specific checklist
      (PSC) to complete the OSAT (which is composed of a PSC and a global rating scale
      [GRS]). The primary objective of this study is to evaluate the performance of a
      novel evaluation strategy for vaginal hysterectomy using an OSAT combining PSC
      and GRS. METHODS: This is a descriptive prospective study from a single
      institution. After orientation to the model, participants were filmed performing
      vaginal hysterectomy. A blinded grader scored each subject using the PSC and GRS.
      RESULTS: Medical students, residents, fellows, and attendings performed vaginal
      hysterectomy on a simulated model. Mean PSC and GRS scores increased
      significantly with surgeon level of experience (P < 0.001). Procedure-specific
      checklist scores significantly correlated with GRS scores (P < 0.001).
      CONCLUSIONS: The vaginal hysterectomy model and PSC have been studied across
      different surgeon levels using OSATs. Training programs should consider using
      this low-cost task trainer as a teaching tool.

PMID- 29443816
TI  - Effects of Osteotomy Lengths on the Temperature Rise of the Crestal Bone During
      Implant Site Preparation.
AB  - AIM: To compare temperatures of the crestal bone during implant site preparation
      for different osteotomy lengths and implant systems. METHODS: Bovine ribs were
      used to simulate the cortical bone of the human mandible. Three different implant
      systems were tested: Astra Tech, Ankylos, and XiVE. Six drills per system were
      performed, meaning each drilling set was used for 2 drills per 3 osteotomy
      lengths (8, 12, and 16 mm). Drilling force, drilling speed, drilling length, and
      temperature were recorded. RESULTS: Differences in the maximum temperature of the
      crestal bone during the first drilling for various osteotomy lengths (P = 0.021)
      and all implant systems (P = 0.013) were observed. A similar result was showed
      during the second drilling; osteotomy lengths (P = 0.014) and drilling systems (P
      = 0.003). Second drillings showed lower temperatures of the crestal bone with
      statistical differences on all measurements (P < 0.001). Astra Tech and Ankylos
      implant systems showed similar performance; XiVE had lower temperature and higher
      temperature differences between osteotomy lengths. CONCLUSIONS: Different
      drilling lengths contributed to the variation in temperature regardless of the
      implant system. Longer drills and osteotomies induced higher temperatures on the
      crestal bone. The maximum temperature difference between the shortest and the
      longest osteotomy was under 1 degrees C. Temperature above 47 degrees C that
      could cause bone necrosis was not recorded at any time. The XiVE system showed
      the best performance.

PMID- 29443814
TI  - Danger Signals in the ICU.
AB  - OBJECTIVES: Sterile and infectious critical illnesses often result in vasoplegic
      shock and a robust systemic inflammatory response that are similar in
      presentation. The innate immune system is at the center of the response to both
      infectious and traumatic insults. Damage-associated molecular patterns are small
      molecules that are released from stressed or dying cells. Damage-associated
      molecular patterns activate pattern recognition receptors and coordinate the
      leading edge of the innate immune response. This review introduces the concept of
      damage-associated molecular patterns and how they activate a systemic
      inflammatory response, specifically in trauma, neurologic injury, and infection.
      It also explores how, when carried to extremes, damage-associated molecular
      patterns may even perpetuate multisystem organ failure. DATA SOURCES: Basic and
      clinical studies were obtained from a PubMed search through August 2017. STUDY
      SELECTION: Articles considered include original articles, review articles, and
      conference proceedings. DATA EXTRACTION: An analysis of scientific, peer-reviewed
      data was performed. High quality preclinical and clinical studies adjudicated by
      the authors were included and summarized. DATA SYNTHESIS: Pattern recognition
      receptors respond to damage-associated molecular patterns and then activate
      inflammatory pathways. Damage-associated molecular patterns have been linked to
      the recruitment of sentinel leukocytes and the initiation of the inflammatory
      cascade. Damage-associated molecular patterns have been linked to many conditions
      in critical care illnesses. Preclinical models have added insight into how they
      may mediate distant organ dysfunction. CONCLUSIONS: Damage-associated molecular
      pattern activation and release is an important research for intensive care
      practitioners. It will add to our understanding of the phase and state of the
      innate immune response to an insult. Early work is encouraging. However, only
      with improved understanding of damage-associated molecular pattern activation and
      function, we can perhaps hope to target damage-associated molecular patterns as
      diagnostic and/or therapeutic modalities in the future.

PMID- 29443817
TI  - Robotic Transthoracic Primary Repair of a Diaphragmatic Hernia and Reduction of
      an Intrathoracic Liver.
AB  - This case involves a 70-year-old woman who presented after a low-speed motor
      vehicle collision with a traumatic right hemidiaphragm rupture and herniation of
      the liver into the right chest. She was brought to the operating room for a
      robotic-assisted minimally invasive transthoracic repair of this hernia with
      diaphragm plication. The case and video described in this report highlight the
      utility of the robotic platform in performing a transthoracic diaphragm repair
      and plication after a right-sided traumatic diaphragm rupture in a patient
      without concomitant abdominal injuries.

PMID- 29443818
TI  - Resection of a Giant-Cell Tumor of the Proximal Aspect of the Radius with
      Osteoarticular Allograft Reconstruction: A Case Report.
AB  - CASE: Giant-cell tumors are locally aggressive osteolytic benign tumors that are
      characterized by multinucleated giant cells. Recurrence rates are <=30% after
      curettage and <5% after resection, but reconstruction can be difficult. We
      describe an osteoarticular allograft reconstruction of the proximal aspect of the
      radius in a 23-year-old man after resection of a giant-cell tumor. CONCLUSION:
      Five months after surgery, the patient had satisfactory joint articulation, range
      of motion, and strength, with no signs of hardware or graft failure. By 17
      months, there was complete osseous union. The joint remained stable at 54 months.
      We describe our surgical approach, which restores joint stability and minimizes
      recurrence.

PMID- 29443819
TI  - Chronic Osteomyelitis with Staphylococcus aureus Deformation in Submicron
      Canaliculi of Osteocytes: A Case Report.
AB  - CASE: A patient presenting with an infected diabetic foot ulcer and
      Staphylococcus aureus chronic osteomyelitis was studied to validate the clinical
      importance of bacterial colonization of osteocytic-canalicular networks, as we
      recently reported in a mouse model. We utilized transmission electron microscopy
      to describe the deformation of S. aureus, from round cocci to rod-shaped
      bacteria, in the submicron osteocytic-canalicular networks of amputated bone
      tissue. CONCLUSION: To our knowledge, this is the first evidence of S. aureus
      deformation and invasion of the osteocytic-canalicular system in human bone,
      which supports a new mechanism of persistence in the pathogenesis of chronic
      osteomyelitis.

PMID- 29443820
TI  - Unstable C1 Fracture Managed with Internal Fixation Using Lateral Mass Screws: A
      Case Report.
AB  - CASE: A 47-year-old woman presented with an unstable C1 fracture after falling
      down several stairs. She was found to have a sagittal split fracture of the right
      C1 lateral mass extending into the posterior arch. The fracture was treated with
      a direct posterior osteosynthesis of C1 using lateral mass screws. CONCLUSION:
      Surgical management of unstable C1 fractures has traditionally involved posterior
      fusion of C1 to C2 or fusion from the occiput to C2. These fusion procedures can
      be quite functionally limiting. Recently, direct osteosynthesis of C1 has been
      shown to be an effective, motion-preserving alternative.

PMID- 29443821
TI  - Changes in Cycling and Incidence of Overweight and Obesity among Danish Men and
      Women.
AB  - PURPOSE: Overweight and obesity are associated with increased risk of several
      noncommunicable diseases and are a growing public health issue. The primary
      purpose of the current study was to investigate incidence of overweight and
      obesity according to 5-yr cycling habits. The secondary purpose was to
      investigate incidence of remission from overweight and obesity according to 5-yr
      cycling habits. METHODS: We analyzed 9014 men and 8661 women without chronic
      disease who between 1993 and 2003 completed two assessments approximately 5 yr
      apart. At both assessments, participants reported habitual cycling habits. Also,
      body weight and waist circumference were measured by a laboratory technician at
      baseline and self-assessed at second examination. We computed multivariable
      adjusted odds ratios (OR) with 95% confidence intervals (CI) for development of
      and remission from abdominal and general overweight and obesity, according to 5
      yr cycling habits. RESULTS: Continued cycling was associated with lower odds for
      incidence of abdominal (men, >102 cm; women, >88 cm) and incidence of general
      (body mass index >=30 kg.m) obesity; compared with no cycling, OR (95% CI) values
      were 0.82 (0.74-0.91) and 0.74 (0.60-0.92) for abdominal and general obesity,
      respectively. Also, those who initiated cycling had lower odds for incidence of
      abdominal obesity; OR (95% CI) was 0.85 (0.73-1.00) relative to no cycling.
      Although we found no evidence of remission from abdominal and general overweight
      and obesity according to 5-yr cycling habits, those who continued cycling had
      significantly larger decreases in waist circumference relative to noncyclists
      (beta coefficient (95% CI), -0.95 cm (-1.56 to -0.33 cm)). CONCLUSIONS: Continued
      cycling compared with no cycling was associated with lower odds for abdominal and
      general obesity. Also, late-in-life initiation of cycling was associated with
      lower odds for abdominal obesity relative to no cycling.

PMID- 29443822
TI  - Power-to-Strength Ratio Influences Performance Enhancement with Contrast
      Training.
AB  - PURPOSE: The effectiveness of contrast training (CST) for improving explosive
      exercise performance is modulated by various individual characteristics; however,
      further work is required to define these factors. METHODS: Subelite male
      Australian Football players (n = 22; age, 19 +/- 2 yr; body mass, 80.4 +/- 9.4
      kg; one-repetition maximum [1-RM] half squat, 172 +/- 18 kg; mean +/- SD)
      completed two experimental trials involving two sets of squat jumps (six
      repetitions at 30% 1-RM) performed either alone (CTL condition) or after half
      squats (six repetitions at 85% 1-RM; CST condition). RESULTS: Squat jump peak
      power was similar between CTL and CST during set 1 (mean change: +/-90%
      confidence interval, 2.8% +/- 2.0%; effect size [ES]: +/-90% confidence interval,
      0.13 +/- 0.09; P = 0.079) and set 2 (0.3% +/- 1.7%; ES, 0.01 +/- 0.08; P =
      0.781). Peak power enhancement with CST was not related to maximal (1-RM half
      squat) strength (r = 0.001, P = 0.884), but was negatively correlated with both
      baseline peak power (r = 0.44, P < 0.001) and power-to-strength ratio (PSR); that
      is, the ratio between baseline peak power and 1-RM half squat strength (r = 0.65,
      P < 0.001). Using a median split, analyses were performed in participants with a
      low PSR (LPSR group; PSR = 15.4-19.1 W.kg; n = 11) or high PSR (HPSR group, PSR =
      19.4-24.7 W.kg; n = 11). Peak power was enhanced with CST for the LPSR (8.1% +/-
      3.9%; ES, 0.44 +/- 0.21; P = 0.004) but not HPSR (-2.1% +/- 1.3%; ES, -0.14 +/-
      0.09; P = 0.010) groups. CONCLUSION: The PSR appears to influence the
      effectiveness of CST, with performance enhancement more likely in those with a
      lower PSR.

PMID- 29443823
TI  - Aerobic Training Improves Quality of Life in Women with Polycystic Ovary
      Syndrome.
AB  - PURPOSE: To investigate the effects of a supervised aerobic exercise training
      intervention on health-related quality of life (HRQL), cardiorespiratory fitness,
      cardiometabolic profile, and affective response in overweight/obese women with
      polycystic ovary syndrome (PCOS). METHODS: Twenty-seven overweight/obese inactive
      women with PCOS (body mass index, >= 25 kg.m; age 18 to 34 yr) were allocated
      into an exercise group (n = 14) and a control group (n = 13). Progressive aerobic
      exercise training was performed three times per week (~150 min.wk) over 16 wk.
      Cardiorespiratory fitness, HRQL, and cardiometabolic profile were evaluated
      before and after the intervention. Affective response (i.e., feeling of
      pleasure/displeasure) was evaluated during the exercise sessions. RESULTS: The
      exercise group improved 21% +/- 12% of cardiorespiratory fitness (P < 0.001) and
      HRQL in the following domains: physical functioning, general health, and mental
      health (P < 0.05). Moreover, the exercise group decreased body mass index, waist
      circumference, systolic and diastolic blood pressure, and total cholesterol level
      (P < 0.05). The affective response varied from "good" to "fairly good" (i.e.,
      positive affective response) in an exercise intensity-dependent manner during the
      exercise training sessions. CONCLUSIONS: Progressive aerobic exercise training
      improved HRQL, cardiorespiratory fitness, and cardiometabolic profile of
      overweight/obese women with PCOS. Moreover, the participants reported the
      exercise training sessions as pleasant over the intervention. These results
      reinforce the importance of supervised exercise training as a therapeutic
      approach for overweight/obese women with PCOS.

PMID- 29443824
TI  - Improving Hip-Worn Accelerometer Estimates of Sitting Using Machine Learning
      Methods.
AB  - PURPOSE: This study aimed to improve estimates of sitting time from hip-worn
      accelerometers used in large cohort studies by using machine learning methods
      developed on free-living activPAL data. METHODS: Thirty breast cancer survivors
      concurrently wore a hip-worn accelerometer and a thigh-worn activPAL for 7 d. A
      random forest classifier, trained on the activPAL data, was used to detect
      sitting, standing, and sit-stand transitions in 5-s windows in the hip-worn
      accelerometer. The classifier estimates were compared with the standard
      accelerometer cut point, and significant differences across different bout
      lengths were investigated using mixed-effect models. RESULTS: Overall, the
      algorithm predicted the postures with moderate accuracy (stepping, 77%; standing,
      63%; sitting, 67%; sit-to-stand, 52%; and stand-to-sit, 51%). Daily level
      analyses indicated that errors in transition estimates were only occurring during
      sitting bouts of 2 min or less. The standard cut point was significantly
      different from the activPAL across all bout lengths, overestimating short bouts
      and underestimating long bouts. CONCLUSIONS: This is among the first algorithms
      for sitting and standing for hip-worn accelerometer data to be trained from
      entirely free-living activPAL data. The new algorithm detected prolonged sitting,
      which has been shown to be the most detrimental to health. Further validation and
      training in larger cohorts is warranted.

PMID- 29443825
TI  - Maternal Influenza Immunization and Prevention of Severe Clinical Pneumonia in
      Young Infants: Analysis of Randomized Controlled Trials Conducted in Nepal, Mali
      and South Africa.
AB  - BACKGROUND: To evaluate the effect of antenatal influenza vaccination on all
      cause severe infant pneumonia, we performed pooled analysis of 3 randomized
      controlled trials conducted in Nepal, Mali and South Africa. METHODS: The trials
      were coordinated from the planning phase. The follow-up period was 0-6 months
      postpartum in Nepal and Mali and 0-24 weeks in South Africa. Pregnant women with
      gestational age 17-34 weeks in Nepal, >=28 weeks in Mali and 20-36 weeks in South
      Africa were enrolled. Trivalent inactivated influenza vaccine (IIV) was compared
      with either saline placebo (Nepal and South Africa) or quadrivalent meningococcal
      conjugate vaccine (Mali). In South Africa, cases were hospitalized and were
      therefore considered to have severe pneumonia. In Nepal and Mali, severe infant
      pneumonia diagnosis was based on the WHO Integrated Management of Childhood
      Illness definition. RESULTS: A total of 10,002 mothers and 9801 live-born
      eligible infants were included in the present analysis. There was a 31% lower
      incidence rate of severe pneumonia in the IIV group compared with the control
      group in Nepal [incidence rate ratio (IRR): 0.69; 95% CI: 0.50-0.94; ]. In South
      Africa, there was a 43% lower incidence rate of severe pneumonia in the IIV group
      versus the control group (IRR: 0.57; 95% CI: 0.33-1.0). There was no difference
      in incidence rates between the IIV group and the control group in Mali. Overall,
      incidence rate of severe pneumonia was 20% lower in the IIV group compared with
      the control group (IRR: 0.80; 95% CI: 0.66-0.99; P = 0.04). Protection was
      highest in the high influenza circulation period (IRR: 0.44; 95% CI: 0.23-0.84).
      CONCLUSIONS: Maternal influenza immunization may reduce severe pneumonia episodes
      among infants-particularly those too young to be completely vaccinated against
      Streptococcus pneumoniae and influenza.

PMID- 29443826
TI  - Higher Risk of Posttransplant Liver Graft Failure in Male Recipients of Female
      Donor Grafts Might Not Be Due to Anastomotic Size Disparity.
AB  - BACKGROUND: Posttransplant liver graft failure occurs most often in male
      recipients of livers from female donors. The respective role of donor sex itself
      and the size disparity in graft vessels/bile ducts according to donor sex are
      unclear. Thus, we aimed to evaluate the importance of donor sex with adjustment
      for anastomotic size disparity between female and male donor grafts. METHODS: A
      total of 309 male patients without hepatic tumors who underwent living donor
      liver transplantation were analyzed (109 female donors and 200 male donors). The
      primary outcome was posttransplant graft failure (ie, retransplantation or
      death). Survival analysis was performed using the Cox model. Analyzed anastomosis
      related factors comprised graft weight, number and size of hepatic vessels/bile
      ducts, and anastomosis techniques. RESULTS: Graft failure probabilities at 1, 6,
      12, 24, and 60 months posttransplantation were 9.1%, 19.5%, 20.2%, 23.0%, and
      27.0%, respectively, with female donors and 2.0%, 5.5%, 8.1%, 10.1%, and 13.5%
      with male donors (hazards ratio [HR], 2.29; 95% confidence interval [CI], 1.35
      3.88; P = 0.002). Multivariable analysis confirmed the significance of donor sex
      (HR, 2.30; 95% CI, 1.14-4.67; P = 0.021) after adjustment for anastomosis-related
      factors. All analyzed anastomosis-related factors showed no significant
      association with graft failure, although size of the graft hepatic artery showed
      marginal significance (HR, 0.50; 95% CI, 0.25-1.01; P = 0.053). The significance
      of donor sex was lost when donor was older than 36 to 40 years (age of poor
      ovarian reserve and the end of female fertility). Our institutional pediatric
      recipient cohort validated the inferiority of female-to-male donation.
      CONCLUSIONS: Donor sex appears to be an independent factor modulating graft
      failure risk in male liver transplant recipients.

PMID- 29443828
TI  - Fat Grafting for Facial Rejuvenation and Contouring: A Rationalized Approach.
AB  - The clinical outcome after fat grafting for facial rejuvenation and contouring
      can be less optimal because lack of standardized techniques is performed by the
      surgeon for the procedure. In this review, the author has tried to provide a
      rationalized approach to fat grafting for facial rejuvenation and contouring. The
      preferred donor sites include low abdomen and inner thigh especially in younger
      patients. Fat grafts should be harvested with low negative pressure via syringe
      liposuction technique to ensure the integrity as well as the optimal level of
      cellular function. Fat grafts should be processed with proper centrifugation that
      can reliably produce purified fat and concentrated growth factors and adipose
      derived stem cells, all of which are beneficial to improve graft survival. Fat
      grafts should be placed after certain principles with gentle injection of small
      amount during the withdraw phase of each pass in multiple tissue planes and
      levels with multiple passes to ensure maximal contact of graft with vascularized
      tissue in the recipient site. The approach described in this review is supported
      by the most recent scientific studies and thus can likely provide a more
      predictable long-lasting result if performed properly.

PMID- 29443827
TI  - A Comparison of HLA Molecular Mismatch Methods to Determine HLA Immunogenicity.
AB  - BACKGROUND: Antibody-mediated rejection is a major cause of premature graft loss
      in kidney transplantation. Multiple scoring systems are available to assess the
      HLA mismatch between donors and recipients at the molecular level; however, their
      correlation with the development of de novo donor-specific antibody (dnDSA) has
      not been compared in recipients on active immunosuppression. METHODS: HLA
      DRbeta1/3/4/5/DQalpha1beta1 molecular mismatch was determined using eplet
      analysis, amino acid mismatch, and electrostatic mismatch for 596 renal
      transplant recipients and correlated with HLA-DR/DQ dnDSA development. The
      molecular mismatch scores were evaluated in multivariate models of posttransplant
      dnDSA-free survival. RESULTS: Eplet mismatch correlated with amino acid mismatch
      and electrostatic mismatch (R = 0.85-0.96). HLA-DR dnDSA-free survival correlated
      with HLA-DR eplet mismatch (hazards ratio [HR], 2.50 per 10 eplets mismatched; P
      < 0.0001), amino acid mismatch (HR, 1.49 per 10 amino acids mismatched; P <
      0.0001), and electrostatic mismatch (HR, 1.23 per 10 units mismatched; P <
      0.0001). HLA-DQ dnDSA-free survival correlated with HLA-DQ eplet mismatch (HR,
      1.98 per 10 eplets mismatched; P < 0.0001), amino acid mismatch (HR, 1.24 per 10
      amino acids mismatched; P < 0.0001), and electrostatic mismatch (HR, 1.14 per 10
      units mismatched; P < 0.0001). All 3 methods were significant multivariate
      correlates of dnDSA development after adjustment for recipient age, baseline
      immunosuppression, and nonadherence. CONCLUSIONS: HLA molecular mismatch
      represents a precise method of alloimmune risk assessment for renal transplant
      patients. The method used to determine the molecular mismatch is likely to be
      driven by familiarity and ease of use as highly correlated results are produced
      by each method.

PMID- 29443830
TI  - The Fifth World Congress for Plastic Surgeons of Chinese Descent.

PMID- 29443831
TI  - Assessment of the Effect of Autograft Orientation on Peripheral Nerve
      Regeneration Using Diffusion Tensor Imaging.
AB  - PURPOSE: Given no definite consensus on the accepted autograft orientation during
      peripheral nerve injury repair, we compare outcomes between reverse and normally
      oriented autografts using an advanced magnetic resonance imaging technique,
      diffusion tensor imaging. METHODS: Thirty-six female Sprague-Dawley rats were
      divided into 3 groups: sham-left sciatic nerve isolation without injury, reverse
      autograft-10-mm cut left sciatic nerve segment reoriented 180 degrees  and used
      to coapt the proximal and distal stumps, or normally oriented autograft-10-mm cut
      nerve segment kept in its normal orientation for coaptation. Animals underwent
      sciatic functional index and foot fault behavior studies at 72 hours, and then
      weekly. At 6 weeks, axons proximal, within, and distal to the autograft were
      evaluated using diffusion tensor imaging and choline acetyltransferase motor
      staining for immunohistochemistry. Toluidine blue staining of 1-MUm sections was
      used to assess axon count, density, and diameter. Bilateral gastrocnemius/soleus
      muscle weights were compared to obtain a net wet weight. Comparison of the groups
      was performed using Mann-Whiney U or Kruskal-Wallis H tests to determine
      significance. RESULTS: Diffusion tensor imaging findings including fractional
      anisotropy, radial diffusivity, and axial diffusivity were similar between
      reverse and normally oriented autografts. Diffusion tensor imaging tractography
      demonstrated proximodistal nerve regeneration in both autograft groups. Motor
      axon counts proximal, within, and distal to the autografts were similar.
      Likewise, axon count, density, and diameter were similar between the autograft
      groups. Muscle net weight at 6 weeks and behavioral outcomes (sciatic functional
      index and foot fault) at any tested time point were also similar between reverse
      and normally oriented autografts. CONCLUSIONS: Diffusion tensor imaging may be a
      useful assessment tool for peripheral nerve regeneration. Reversing nerve
      autograft polarity did not demonstrate to have an influence on functional or
      regenerative outcomes.

PMID- 29443832
TI  - One-Barrel Microsurgical Fibula Flap for Reconstruction of Large Defects of the
      Femur.
AB  - Various methods for reconstructing large femur bone defects after tumor resection
      have been introduced. In this study, we reviewed the clinical outcomes of using a
      1-barrel free vascularized fibular graft (FVFG) protected by a lateral locking
      plate for large femoral defects not involving the knee joint.Between August 2007
      and August 2013, we treated 7 patients with large femoral bone defects after
      tumor resection. The mean age of the patients was 19 years (range, 12-36 years),
      and 3 were women. All defects were free of infection before the procedure.
      Femoral bone defects were reconstructed using a 1-barrel FVFG protected by a
      lateral locking plate. The mean bone defect size was 10.5 cm (range, 6-16 cm). We
      reviewed clinical outcomes at the last follow-up.All patients survived beyond the
      last follow-up; the mean follow-up period was 54 months (range, 26-100 months).
      Two patients sustained stress fractures of the FVFG, but the lateral locking
      plate protected the fractured graft until in situ bone healing obtained. Mean
      time to bone union of both host-graft junctions was 24 months (range, 18-31
      months). The mean Musculoskeletal Tumor Society score (%) was 85.8% (range, 80
      95%).A 1-barrel FVFG protected by a lateral locking plate maintained a stable
      graft-host bone construct, successfully leading to bone healing, even in cases of
      stress fractures of the graft, and appears to be a good option for large femur
      bone defects.

PMID- 29443834
TI  - Does 2-Stage Implant-Based Breast Reconstruction Allow for a Larger Volume of the
      Definite Implant Compared With 1-Stage Reconstruction?
AB  - INTRODUCTION: Breast reconstruction using implants is still the main breast
      reconstruction technique worldwide. Current debate within implant-based breast
      reconstruction is whether to perform a 1-stage (direct implant) or 2-stage
      (tissue expander/implant) reconstruction. Volume differences between a woman's
      native breast and changes in volume after breast reconstruction might be an
      important factor for a patient's choice between these types of reconstruction.
      Three-dimensional imaging facilitates objective breast volume estimates. The goal
      of this study was to investigate differences between the patient's natural breast
      and the volume after completed breast reconstruction. One- and two-stage implant
      based breast reconstruction techniques were compared. Finally, it was assessed
      whether patient satisfaction is causally related with the final breast volume
      after reconstruction. METHODS AND RESULTS: A total of 38 patients were included
      in the study, including 35 two-stage breast reconstructions and 27 one-stage
      reconstructions. Preoperative and postoperative 3-dimensional images of the
      breast with the Vectra XT Imaging system were taken. Volume analysis was
      performed to estimate the patient's native breast volume. Implant size were
      derived from the operation report. A mean volume reduction for the 1-stage
      reconstruction group was found -1 mL, whereas an increase of +80 mL was found in
      the 2-stage reconstruction group (P < 0.005). Patient satisfaction related to
      volume outcome was not significantly different between both groups, using the
      Breast-Q questionnaire. CONCLUSIONS: This study shows that a 2-stage breast
      reconstruction has the potential of an increased breast volume compared with a
      similar breast volume in 1-stage reconstruction.

PMID- 29443833
TI  - Experimental Study on Effects of Adipose-Derived Stem Cell-Seeded Silk Fibroin
      Chitosan Film on Wound Healing of a Diabetic Rat Model.
AB  - BACKGROUND: Wound healing is a complex process that relies on growth factors and
      stimulation of angiogenesis. Tissue engineering materials composed of adipose
      derived stem cells (ADSCs) and silk fibroin (SF)/chitosan (CS) may be able to
      solve this problem. The aim of this study was to investigate the wound-healing
      potential of ADSC-seeded SF/CS in streptozotocin-induced diabetic rats. MATERIALS
      AND METHODS: Thirty-six male Sprague-Dawley rats were purchased and randomly
      assigned into 3 groups: a control group (no graft), a group treated with SF/CS
      film graft, and a group treated with ADSC-seeded SF/CS graft. The number of
      animals in each group was 12. Diabetes was induced by an intraperitoneal
      injection of streptozotocin. A cutaneous wound was incised at the dorsal region
      of all the experimental animals. The ADSCs were labeled with CM-Dil fluorescent
      staining. Wound healing was assessed for all animal groups by observing the rate
      of wound closure and hematoxylin and eosin staining. The expression of epidermal
      growth factor, transforming growth factor-beta, and vascular endothelial growth
      factor at the wound sites was studied by enzyme-linked immunosorbent assay to
      evaluate the effect of growth factors secreted by ADSCs. The differentiation of
      ADSCs was analyzed by immunofluorescence staining. RESULTS: The ADSC-seeded SF/CS
      film treatment significantly increased the rates of wound closure in treated
      animals, and hence wound healing was drastically enhanced for ADSC-SF/CS
      treatment groups compared with control groups and SF/CS film treatment group.
      Histological observations showed the condition of wound healing. Enzyme-linked
      immunosorbent assay and immunofluorescence staining observations showed the
      secretion and differentiation of ADSCs, respectively. CONCLUSIONS: Our analyses
      clearly suggested that it is feasible and effective to enhance wound healing in a
      diabetic rat model with ADSC-seeded SF/CS film.

PMID- 29443835
TI  - Venous Thromboembolism Incidence After Craniofacial Surgery.
AB  - INTRODUCTION: Current protocols for venous thromboembolism (VTE) prophylaxis
      after craniofacial surgery (CFS) vary widely with substantial disagreements in
      both indications and managements. An evidence-based approach to this issue
      requires the following: the incidence of postoperative VTE, comorbidities
      associated with coagulopathy, risk reduction after VTE prophylaxis, and
      complications attributable to prophylaxis. This study addresses the first two.
      DESIGN: Retrospective cross-sectional study. METHODS: Discharge data from 64,170
      patients undergoing CFS between 2008 and 2013 extracted from the Healthcare Cost
      and Utilization Project Nationwide Inpatient Sample were analyzed. The outcome
      measures extracted were: deep venous thrombosis, pulmonary embolism, demographic
      data, common comorbidities, length of stay, total cost, and discharge outcome.
      RESULTS: Diagnoses of deep venous thrombosis or pulmonary embolism, collectively
      classified as VTE, were observed in 355 (0.55%) of 64,170 patients discharged
      after CFS. Other surgeries exhibited a VTE rate of 1.17%. Men exhibited nearly
      double the incidence of VTE relative to women (0.69% compared with 0.37%
      respectively, P < 0.001), and the risk factors of adulthood, advanced age,
      cardiovascular disease, obesity, and malignancy were associated with increased
      VTE incidence with odds ratios of 9.93, 3.66, 1.80, 2.02, and 2.02, respectively
      (P < 0.005). Tobacco use did not exhibit any significant association (odds ratio,
      0.94; P = 0.679). Afflicted patients experienced 4.60 times longer hospital stays
      averaging 23.8 days (95% confidence interval, 21.4-26.2; P < 0.001) compared the
      average of 5.2 days experienced by CFS patients without VTE. They incurred an
      average cost of US $298,228 (95% confidence interval, 262,726 to 333,731; P <
      0.001) which was 4.17 times the US $72,376 expense of treating other CFS
      patients. The likelihood for a CFS patient to experience a poor outcome at the
      time of discharge was 54.6% higher after VTE. CONCLUSIONS: The risk of
      postoperative VTE after CFS is significantly increased in adults, patients with
      advanced age, cardiovascular disease, obesity, and malignancy. However even in
      those high-risk cases, postoperative VTE incidence remains relatively low after
      CFS. These findings in conjunction with further study regarding the risk
      associated with the addition of VTE chemoprophylaxis compared against mechanical
      VTE prophylaxis, such as sequential pneumatic compression stockings, may
      determine whether routine use of VTE chemoprophylaxis is appropriate.

PMID- 29443836
TI  - Course Review: AOTrauma-Hand Fixation for Surgeons.
AB  - Hand trauma forms an important part of plastic surgery and orthopedic training
      curricula. Although numerous practical hand trauma courses exist, there is always
      difficulty in achieving the right balance between educational content and
      practical workshops. AOTrauma-Hand Fixation for Surgeons is a 2.5-day course for
      plastic surgery and orthopedic trainees that aims to instill the principles of
      hand fracture fixation and soft tissue coverage through self-directed learning,
      lectures, small group discussion, and dry bone practical workshops. This course
      with international faculty and delegates is held in Leeds, United Kingdom, at a
      cost of 860 Swiss francs (880 US dollars). In this review, we provide an
      evaluation of the course.

PMID- 29443838
TI  - Editor's Spotlight/Take 5: How Common-and How Serious-Is Clostridium difficile
      Colitis After Geriatric Hip Fracture? Findings from the NSQIP Dataset.

PMID- 29443837
TI  - Editorial: Orthopaedic Heroes-Here are Mine, Who are Yours?

PMID- 29443839
TI  - How Common-and How Serious- Is Clostridium difficile Colitis After Geriatric Hip
      Fracture? Findings from the NSQIP Dataset.
AB  - BACKGROUND: Patients with geriatric hip fractures may be at increased risk for
      postoperative Clostridium difficile colitis, which can cause severe morbidity and
      can influence hospital quality metrics. However, to our knowledge, no large
      database study has calculated the incidence of, factors associated with, and
      effect of C. difficile colitis on geriatric patients undergoing hip fracture
      surgery. QUESTIONS/PURPOSES: To use a large national database with in-hospital
      and postdischarge data (National Surgical Quality Improvement Program [NSQIP(r)])
      to (1) determine the incidence and timing of C. difficile colitis in geriatric
      patients who underwent surgery for hip fracture, (2) identify preoperative and
      postoperative factors associated with the development of C. difficile colitis in
      these patients, and (3) test for an association between C. difficile colitis and
      postoperative length of stay, 30-day readmission, and 30-day mortality. PATIENTS
      AND METHODS: This is a retrospective study. Patients who were 65 years or older
      who underwent hip fracture surgery were identified in the 2015 NSQIP database.
      The primary outcome was a diagnosis of C. difficile colitis during the 30-day
      postoperative period. Preoperative and procedural factors were tested for
      association with the development of C. difficile colitis through a backward
      stepwise multivariate model. Perioperative antibiotic type and duration were not
      included in the model, as this information was not recorded in the NSQIP. The
      association between C. difficile colitis and postoperative length of stay, 30-day
      readmission, and 30-day mortality were tested through multivariate regressions,
      which adjusted for preoperative and procedural characteristics such as age,
      comorbidities, and surgical procedure. A total of 6928 patients who were 65 years
      or older and underwent hip fracture surgery were identified. RESULTS: The
      incidence of postoperative C. difficile colitis was 1.05% (95% CI, 0.81%-1.29%;
      73 of 6928 patients). Of patients who had C. difficile colitis develop, 64% (47
      of 73 patients) were diagnosed postdischarge and 79% (58 of 73 patients) did not
      have a preceding infectious diagnosis. Preoperative factors identifiable before
      surgery that were associated with the development of C. difficile colitis
      included admission from any type of chronic care facility (versus admitted from
      home; relative risk [RR] = 1.98; 95% CI, 1.11-3.55; p = 0.027), current smoker
      within 1 year (RR = 1.95; 95% CI, 1.03-3.69; p = 0.041), and preoperative anemia
      (RR = 1.76; 95% CI, 1.07-2.92; p = 0.027). Patients who had pneumonia (RR = 2.58;
      95% CI, 1.20-5.53; p = 0.015), sepsis (RR = 4.20; 95% CI, 1.27-13.82; p = 0.018),
      or "any infection" (RR = 2.26; 95% CI, 1.26-4.03; p = 0.006) develop after hip
      fracture were more likely to have C. difficile colitis develop. Development of C.
      difficile colitis was associated with greater postoperative length of stay (22
      versus 5 days; p < 0.001), 30-day readmission (RR = 3.41; 95% CI, 2.17-5.36; p <
      0.001), and 30-day mortality (15% [11 of 73 patients] versus 6% [439 of 6855
      patients]; RR = 2.16; 95% CI, 1.22-3.80; p = 0.008). CONCLUSIONS: C. difficile
      colitis is a serious infection after hip fracture surgery in geriatric patients
      that is associated with 15% mortality. Patients at high risk, such as those
      admitted from any type of chronic care facility, those who had preoperative
      anemia, and current smokers within 1 year, should be targeted with preventative
      measures. From previous studies, these measures include enforcing strict hand
      hygiene with soap and water (not alcohol sanitizers) if a provider is caring for
      patients at high risk and those who are C. difficile-positive. Further, other
      studies have shown that certain antibiotics, such as fluoroquinolones and
      cephalosporins, can predispose patients to C. difficile colitis. These
      medications perhaps should be avoided when prescribing prophylactic antibiotics
      or managing infections in patients at high risk. Future prospective studies
      should aim to determine the best prophylactic antibiotic regimens, probiotic
      formula, and discharge timing that minimize postoperative C. difficile colitis in
      patients with hip fractures. LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 29443840
TI  - Cochrane in CORR(r): Negative Pressure Wound Therapy for Skin Grafts and Surgical
      Wounds Healing by Primary Intention.

PMID- 29443841
TI  - Medicolegal Sidebar: Serving on the Sidelines-The American Football Dilemma.

PMID- 29443842
TI  - CORR International-Asia Pacific: Is Price Capping of Knee Replacement Implants in
      India a Good Idea?

PMID- 29443843
TI  - On Patient Safety: Are Online Reviews a Reliable Assessment of Safety?

PMID- 29443844
TI  - Residency Diary: Fight With Everything You Have.

PMID- 29443845
TI  - Raising the Joint Line in TKA is Associated With Mid-flexion Laxity: A Study in
      Cadaver Knees.
AB  - BACKGROUND: In a typical osteoarthritic knee with varus deformity, distal femoral
      resection based off the worn medial femoral condyle may result in an elevated
      joint line. In a setting of fixed flexion contracture, the surgeon may choose to
      resect additional distal femur to obtain extension, thus purposefully raising the
      joint line. However, the biomechanical effect of raising the joint line is not
      well recognized. QUESTIONS/PURPOSES: (1) What is the effect of the level of the
      medial joint line (restored versus raised) on coronal plane stability of a TKA?
      (2) Does coronal alignment technique (mechanical axis versus kinematic technique)
      affect coronal plane stability of the knee? (3) Can the effect of medial joint
      line elevation on coronal plane laxity be predicted by an analytical model?
      METHODS: A TKA prosthesis was implanted in 10 fresh frozen nonarthritic cadaveric
      knees with restoration of the medial joint line at its original level (TKA0).
      Coronal plane stability was measured at 0 degrees , 30 degrees , 60 degrees , 90
      degrees , and 120 degrees  flexion using a navigation system while applying an
      instrumented 9.8-Nm varus and valgus force moment. The joint line then was raised
      in two steps by recutting the distal and posterior femur by an extra 2 mm (TKA2)
      and 4 mm (TKA4), downsizing the femoral component and, respectively, adding a 2-
      and a 4-mm thicker insert. This was done with meticulous protection of the
      ligaments to avoid damage. Second, a simplified two-dimensional analytical model
      of the superficial medial collateral ligament (MCL) length based on a single
      flexion-extension axis was developed. The effect of raising the joint line on the
      length of the superficial MCL was simulated. RESULTS: Despite that at 0 degrees 
      (2.2 degrees  +/- 1.5 degrees  versus 2.3 degrees  +/- 1.1 degrees  versus 2.5
      degrees  +/- 1.1 degrees ; p = 0.85) and 90 degrees  (7.5 degrees  +/- 1.9
      degrees  versus 9.0 degrees  +/- 3.1 degrees  versus 9.0 degrees  +/- 3.5 degrees
      ; p = 0.66), there was no difference in coronal plane laxity between the TKA0,
      TKA2, and TKA4 positions, increased laxity at 30 degrees  (4.8 degrees  +/- 1.9
      degrees  versus 7.9 degrees  +/- 2.3 degrees  versus 10.2 degrees  +/- 2.0
      degrees ; p < 0.001) and 60 degrees  (5.7 degrees  +/- 2.7 degrees  versus 8.8
      degrees  +/- 2.9 degrees  versus 11.3 degrees  +/- 2.9 degrees ; p < 0.001) was
      observed when the medial joint line was raised 2 and 4 mm. At 30 degrees , this
      corresponds to an average increase of 64% (3.1 degrees ; p < 0.01) in mid-flexion
      laxity with a 2-mm raised joint line and a 111% (5.4 degrees ; p < 0.01) increase
      with a 4-mm raised joint line compared with the 9-mm baseline resection. No
      differences in coronal alignment were found between the knees implanted with
      kinematic alignment versus mechanical alignment at any flexion angle. The
      analytical model was consistent with the cadaveric findings and showed
      lengthening of the superficial MCL in mid-flexion. CONCLUSIONS: Despite a well
      balanced knee in full extension and at 90 degrees  flexion, increased mid-flexion
      laxity in the coronal plane was evident in the specimens where the joint line was
      raised. CLINICAL RELEVANCE: When recutting the distal and posterior femur and
      downsizing the femoral component, surgeons should be aware that this action might
      increase the laxity in mid-flexion, even if the knee is stable at 0 degrees  and
      90 degrees .

PMID- 29443846
TI  - CORR Insights(r): Validation of the Chinese (Mandarin) Version of the Oxford Knee
      Score in Patients with Knee Osteoarthritis.

PMID- 29443847
TI  - CORR Insights(r): Current Total Knee Designs: Does Baseplate Roughness or Locking
      Mechanism Design Affect Polyethylene Backside Wear?

PMID- 29443848
TI  - CORR Insights(r): Polyethylene Damage Increases With Varus Implant Alignment in
      Posterior-stabilized and Constrained Condylar Knee Arthroplasty.

PMID- 29443849
TI  - CORR Insights(r): Many Shoulder MRI Findings in Elite Professional Throwing
      Athletes Resolve After Retirement: A Clinical and Radiographic Study.

PMID- 29443850
TI  - Does an Algorithmic Approach to Using Brachytherapy and External Beam Radiation
      Result in Good Function, Local Control Rates, and Low Morbidity in Patients With
      Extremity Soft Tissue Sarcoma?
AB  - BACKGROUND: High-dose-rate brachytherapy (HDR-BT) and external-beam radiation
      therapy (EBRT) are two modalities used in the treatment of soft tissue sarcoma.
      Previous work at our institution showed early complications and outcomes for
      patients treated with HDR-BT, EBRT, or a combination of both radiation therapy
      modalities. As the general indications for each of these approaches to radiation
      therapy differ, it is important to evaluate the use of each in an algorithmic
      way, reflecting how they are used in contemporary practice at sites that use
      these treatments. QUESTION/PURPOSES: (1) To determine the proportions of
      intermediate- and long-term complications associated with the use of
      brachytherapy in the treatment of primary high-grade extremity soft tissue
      sarcomas; (2), to characterize the long-term morbidity of the three radiation
      treatment groups using the Radiation Therapy Oncology Group/ European
      Organization for Research and Treatment of Cancer (RTOG/EORTC) Late Radiation
      Morbidity Scoring Scheme; (3) to determine whether treatment with HDR-BT, EBRT,
      and HDR-BT+EBRT therapy, in combination with limb-salvage surgery, results in
      acceptable local control in this high-risk group of sarcomas. METHODS: We
      retrospectively studied data from 171 patients with a diagnosis of high-grade
      extremity soft tissue sarcoma treated with limb-sparing surgery and radiation
      therapy between 1990 and 2012 at our institution, with a mean followup of 72
      months. Of the 171 patients, 33 (20%) were treated with HDR-BT, 128 (75%) with
      EBRT, and 10 (6%) with HDR-BT+EBRT. We excluded 265 patients with soft tissue
      sarcomas owing to axial tumor location, previous radiation to the affected
      extremity, incomplete patient records, patients receiving primary amputation,
      recurrent tumors, pediatric patients, low- and intermediate-grade tumors, and
      rhabdoid histology. Fifteen patients (9%) were lost to followup for any reason
      including died of disease or other causes during the first 12 months
      postoperatively. This included four patients who received HDR-BT (12%), 11 who
      received EBRT (9%), and none who received HDR-BT+EBRT (0%) with less than 12
      months followup. Determination of radiation therapy technique for each patient
      was individualized in a multidisciplinary forum of sarcoma specialists.
      Anticipated close or positive surgical margins and a low likelihood of complex
      soft tissue procedures were factors that encouraged use of brachytherapy, whereas
      the anticipated need for secondary procedures and/or soft tissue coverage
      encouraged use of EBRT alone. Combination therapy was used when the treatment
      volume exceeded the treatment field of the brachytherapy catheters or when the
      catheters were used to boost a close or positive surgical margin. Local
      recurrence, complications, and morbidity outcomes scores (RTOG) were calculated
      based on chart review. Between-group comparisons pertaining to the proportion of
      patients experiencing complications, morbidity outcomes scores, and local
      recurrence rates were not performed because of dissimilarities among the patients
      in each group at baseline. RESULTS: The HDR-BT treatment group showed a high
      incidence of intermediate-term complications, with the three most common being:
      deep infection (33%, 11 of 33); dehiscence and delayed wound healing (24%, eight
      of 33); and seroma and hematoma (21%, seven of 33). The EBRT group showed a high
      incidence of intermediate- and long-term complications with the three most common
      being: chronic radiation dermatitis (35%, 45 of 128); fibrosis (27%, 35 of 128);
      and chronic pain and neuritis (13%, 16 of 128). The RTOG scores for each
      treatment group were: HDR-BT 0.8 +/- SD 1.2; EBRT 1.9 +/- 2.0; and HDR-BT+EBRT
      1.7 +/- 1.7. Overall, 142 of 169 (84%) patients were free from local recurrence:
      27 (82%) in the HDR-BT group, 108 (86%) in the EBRT group, and seven (70%) in the
      combination therapy group. CONCLUSIONS: In this single-institution study, an
      algorithmic approach to using HDR-BT and EBRT in the treatment of patients with
      high-grade soft tissue sarcomas can yield acceptable complication rates, good
      morbidity outcome scores, and a high degree of local control. Based on these
      results, we believe HDR-BT is best for patients with an anticipated close margin,
      a positive surgical margin, and for patients who are unlikely to receive a
      complex soft tissue procedure. Conversely, if a secondary procedure and/or soft
      tissue coverage are likely to be used, EBRT alone may be reasonable. Finally,
      combination therapy might be considered when the treatment volume exceeded the
      treatment field capacity for HDR-BT or when the catheters were used to boost a
      close or positive surgical margin. LEVEL OF EVIDENCE: Level IV, therapeutic
      study.

PMID- 29443851
TI  - CORR Insights(r): Does an Algorithmic Approach to Using Brachytherapy and
      External Beam Radiation Result in Good Function, Local Control Rates, and Low
      Morbidity in Patients With Extremity Soft Tissue Sarcoma?

PMID- 29443852
TI  - Chlorhexidine Antiseptic Irrigation Eradicates Staphylococcus epidermidis From
      Biofilm: An In Vitro Study.
AB  - BACKGROUND: Antiseptic and antibacterial solutions used for intraoperative
      irrigation are intended to kill bacteria and thereby decrease the incidence of
      surgical site infections. It is unknown if the concentrations and exposure times
      of irrigation solutions commonly used for prophylaxis in clean cases (povidone
      iodine 0.35% for 3 minutes) are effective against bacteria in biofilm that are
      present in implant infections. Currently, povidone-iodine (0.35%), chlorhexidine
      (0.05%), sodium hypochlorite (0.125%), and triple antibacterial solution are all
      being used off-label for wound irrigation after surgical debridement for
      orthopaedic infections. QUESTIONS/PURPOSES: Do commonly used antibacterials and
      antiseptics kill bacteria in established biofilm at clinically relevant
      concentrations and exposure times? METHODS: Staphylococcus epidermidis
      (ATCC#35984) biofilms were exposed to chlorhexidine (0.025%, 0.05%, and 0.1%),
      povidone-iodine (0.35%, 1.0%, 3.5%, and 10%), sodium hypochlorite (0.125%, 0.25%,
      and 0.5%,), and triple antibacterial solution (bacitracin 50,000 U/L, gentamicin
      80 mg/L, and polymyxin 500,000 U/L) for 1, 5, and 10 minutes in triplicate.
      Surviving bacteria were detected by 21-day subculture. Failure to eradicate all
      bacteria in any of the three replicates was considered to be "not effective" for
      that respective solution, concentration, and exposure time. RESULTS:
      Chlorhexidine 0.05% and 0.1% at all three exposure times, povidone-iodine 10% at
      all three exposure times, and povidone-iodine 3.5% at 10 minutes only were
      effective at eradicating S epidermidis from biofilm. All concentrations and all
      exposure times of sodium hypochlorite and triple antibacterial solution were not
      effective. CONCLUSIONS: Chlorhexidine is capable of eradicating S epidermidis
      from biofilm in vitro in clinically relevant concentrations and exposure times.
      Povidone-iodine at commonly used concentrations and exposure times, sodium
      hypochlorite, and triple antibacterial solutions are not. CLINICAL RELEVANCE:
      This in vitro study suggests that chlorhexidine may be a more effective
      irrigation solution for S epidermidis in biofilm than other commonly used
      solutions, such as povidone-iodine, Dakin's solution, and triple antibiotic
      solution. Clinical outcomes should be studied to determine the most effective
      antiseptic agent, concentration, and exposure time when intraoperative irrigation
      is used in the presence of biofilm.

PMID- 29443853
TI  - CORR Insights(r): Chlorhexidine Antiseptic Irrigation Eradicates Staphylococcus
      epidermidis From Biofilm: An In Vitro Study.

PMID- 29443854
TI  - Universal screening for intimate partner and sexual violence in trauma patients
      What about the men? An Eastern Association for the Surgery of Trauma Multicenter
      Trial.
AB  - BACKGROUND: A recent Eastern Association for the Surgery of Trauma-supported
      multicenter trial demonstrated a similar rate of intimate partner and sexual
      violence (IPSV) between male and female trauma patients, regardless of mechanism.
      Our objective was to perform a subgroup analysis of our affected male cohort
      because this remains an understudied group in the trauma literature. METHODS: We
      conducted a recent Eastern Association for the Surgery of Trauma-supported, cross
      sectional, multicenter trial over one year (March 2015 to April 2016) involving
      four Level I trauma centers throughout the United States. We performed universal
      screening of adult trauma patients using the validated Hurt, Insult, Threaten,
      Scream and sexual violence screening surveys. Risk factors for male patients were
      identified. chi Test compared categorical variables with significance at p values
      less than 0.05. Parametric data are presented as mean +/- standard deviation.
      RESULTS: A total of 2,034 trauma patients were screened, of which 1,281 (63%)
      were men. Of this cohort, 119 (9.3%) men screened positive for intimate partner
      violence, 14.1% for IPSV, and 6.5% for sexual violence. On categorical analysis
      of the Hurt, Insult, Threaten, Scream screen, the proportion of men that were
      physically hurt was 4.8% compared to 4.3% for women (p = 0.896). A total of 4.8%
      of men screened positive for both IPSV. The total proportion of men who presented
      with any history of intimate partner violence, sexual violence, or both (IPSV)
      was 15.8%. More men affected by penetrating trauma screened positive for IPSV (p
      < 0.00001). The IPSV positivity in men was associated with mental illness,
      substance abuse, and trauma recidivism. CONCLUSION: One of every 20 men that
      present to trauma centers is a survivor of both IPSV, with one of every six men
      experiencing some form of violence. Men are at similar risk for physical abuse as
      women when this intimate partner violence occurs. The IPSV is associated with
      penetrating trauma in men. Support programs for this population may potentially
      impact associated mental illness, substance abuse, trauma recidivism, and even
      societal-level violence. LEVEL OF EVIDENCE: Epidemiological study, level II.

PMID- 29443855
TI  - Continuous remote ischemic conditioning attenuates cognitive and motor deficits
      from moderate traumatic brain injury.
AB  - BACKGROUND: While studies show that single-dose remote ischemic conditioning
      (RIC) improves outcomes, the effect of continuous (daily) RIC is unknown. Thus,
      we aimed to investigate the role of continuous RIC on cognitive and motor
      function following traumatic brain injury (TBI). METHODS: We subjected 24 male
      C57BL mice to a cortical-controlled TBI. Two hours after TBI, the animals were
      randomly allocated to the RIC group (n = 12) or the sham group (n = 12). Remote
      ischemic conditioning was induced by noninvasive external compression of the hind
      limb using an occlusive band (six 4-minute cycles/24 hours) for six consecutive
      days. Before TBI, a baseline rotarod test and novel object recognition were
      performed. Post-TBI rotarod and novel object recognition tests were performed on
      Days 1 to 5, 7, 14, and 21. After the animals were sacrificed on Day 21, brain
      sections were analyzed using hematoxylin and eosin and glial fibrillary acidic
      protein staining to evaluate the hippocampal CA1 area for neuronal injury.
      RESULTS: Both the RIC and sham groups had lower latency to fall compared with the
      baseline post-TBI. The RIC animals had a higher latency to fall compared with the
      sham animals at all time points, statistically significant after Day 3, until Day
      21 post-TBI. Both the RIC and sham groups had lower recognition index compared
      with the baseline post-TBI. The RIC animals had a significantly higher
      recognition index than the sham animals after Day 1, until Day 21 post-TBI.
      Hematoxylin and eosin and glial fibrillary acidic protein staining of the brain
      samples of the sham group revealed that more neurons in the hippocampal CA1 area
      appeared shrunken with eosinophilic cytoplasm and pyknotic nuclei compared with
      the brain samples of the RIC group. CONCLUSION: Postinjury continuous RIC
      resulted in improved cognitive functions and motor coordination in a mouse model
      of moderate TBI. Further studies are required to determine optimum dosage and
      frequency of this novel therapy to maximize its beneficial effects following TBI.

PMID- 29443856
TI  - Complications in tube thoracostomy: Systematic review and meta-analysis.
AB  - BACKGROUND: Tube thoracostomy (TT) complications and their reported rates are
      highly variable (1-40%) and inconsistently classified. Consistent TT complication
      classification must be applied to compare reported literature to standardize TT
      placement. We aim to determine the overall TT-related complication rates in
      patients receiving TT for traumatic indications using uniform definitions.
      METHODS: Systematic review and meta-analysis was performed assessing TT-related
      complications. Comprehensive search of several databases (1975-2015) was
      conducted. We included studies that reported on bedside TT insertion (>=22 Fr) in
      trauma patients. Data were abstracted from eligible articles by independent
      reviewers with discrepancies reconciled by a third. Analyses were based on
      complication category subtypes: insertional, positional, removal,
      infection/immunologic/education, and malfunction. RESULTS: Database search
      resulted in 478 studies; after applying criteria 29 studies were analyzed
      representing 4,981 TTs. Injury mechanisms included blunt 60% (49-71), stab 27%
      (17-34), and gunshot 13% (7.8-10). Overall, median complication rate was 19% (95%
      confidence interval, 14-24.3). Complication subtypes included insertional
      (15.3%), positional (53.1%), removal (16.2%), infection/immunologic (14.8%), and
      malfunction (0.6%). Complication rates did not change significantly over time for
      insertional, immunologic, or removal p = 0.8. Over time, there was a decrease in
      infectious TT-related complications as well as an increase in positional TT
      complications. CONCLUSION: Generation of evidence-based approaches to improve TT
      insertion outcomes is difficult because a variety of complication classifications
      has been used. This meta-analysis of complications after TT insertion in trauma
      patients suggests that complications have not changed over time remaining stable
      at 19% over the past three decades. LEVEL OF EVIDENCE: Systematic review and meta
      analysis, level III.

PMID- 29443857
TI  - The FAST Exam Can Reliably Identify Patients with Significant Intraabdominal
      Hemorrhage in Life Threatening Pelvic Fractures.
AB  - BACKGROUND: The Focused Abdominal Sonography for Trauma (FAST) exam has been
      reported to be unreliable in pelvic fracture patients. Additionally, given the
      advent of new therapeutic interventions, such as Resuscitative Endovascular
      Balloon Occlusion of the Aorta (REBOA), rapid identification of intraabdominal
      hemorrhage compared to zone III hemorrhage may guide different therapeutic
      strategies. We hypothesized that FAST is reliable for detecting clinically
      significant intraabdominal hemorrhage in the face of complex pelvic fractures.
      METHODS: Our pelvic fracture database of all hemodynamically unstable patients
      requiring intervention from 1/1/05 to 7/1/15 was reviewed. FAST exam was compared
      to operative and CT scan findings. Confirmatory evaluation for FAST(-) patients
      was considered positive if therapeutic intervention was required. RESULTS: During
      the study period, 81 patients in refractory shock with FAST imaging in our ED
      underwent pelvic packing. Mean age was 45 +/- 2 years and ISS was 50 +/- 1.5. The
      FAST exam was negative in 53 patients; 52 patients did not require operative
      intervention for abdominal bleeding while 1 patient required splenectomy. FAST
      exam was positive in 28 patients; 26 had findings confirmed by CT or laparotomy
      while 2 patients did not have intraabdominal hemorrhage on further evaluation.
      The sensitivity and specificity for FAST in this population was 96% and 96%; PPV
      was 93% and NPV was 98%. The false negative and positive rates for FAST were 2%
      and 7%. CONCLUSIONS: FAST reliably identifies clinically significant
      hemoperitoneum in life-threatening, pelvic fracture related hemorrhage. The
      incidence of a false negative FAST in this unstable pelvic fracture population
      was 2%. FAST results may be used when determining the role of REBOA in these
      multisystem trauma patients and requires further study. REBOA placement should be
      considered in hemodynamically unstable pelvic fracture patients who are FAST(-),
      while laparotomy should be used in FAST(+) patients. LEVEL OF EVIDENCE: Level
      III, case control series for therapeutic/prognostic management.

PMID- 29443858
TI  - Measurement of compensatory reserve predicts racial differences in tolerance to
      simulated hemorrhage in women.
AB  - BACKGROUND: The compensatory reserve measurement (CRM) has been established to
      accurately measure the body's total integrated capacity to compensate for
      physiologic states of reduced central blood volume and predict hemodynamic
      decompensation associated with inadequate tissue oxygenation. We previously
      demonstrated that African American (AA) women have a higher tolerance to
      reductions in central blood volume. Therefore, we tested the hypothesis that the
      CRM would identify racial differences during simulated hemorrhage, before the
      onset of traditional signs/symptoms. METHODS: We performed a retrospective
      analysis during simulated hemorrhage using lower-body negative pressure (LBNP) in
      23 AA (22 +/- 1 years; 24 +/- 1 kg/m) and 31 white women (WW) (20 +/- 1 years; 23
      +/- 1 kg/m). Beat-by-beat blood pressure (BP) and heart rate (HR) were recorded
      during progressive lower body negative pressure to presyncope. The BP waveforms
      were analyzed using a machine-learning algorithm to derive the CRM at each lower
      body negative pressure stage. RESULTS: Resting mean arterial BP (AA, 78 +/- 3 mm
      Hg vs. WW, 74 +/- 2 mm Hg) and HR (AA, 68 +/- 2 bpm vs. WW, 65 +/- 2 bpm) were
      similar between groups. The CRM progressively decreased during LBNP in both
      groups; however, the rate of decline in the CRM was less (p < 0.05) in AA. The
      CRM was 4% higher in AA at -15 mm Hg LBNP and progressively increased to 21%
      higher at -50 mm Hg LBNP (p < 0.05). However, changes in BP and HR were not
      different between groups. CONCLUSION: These data support the notion that the
      greater tolerance to simulated hemorrhage induced by LBNP in AA women can be
      explained by their greater capacity to protect the reserve to compensate for
      progressive central hypovolemia compared with WW, independent of standard vital
      signs. LEVEL OF EVIDENCE: Diagnostic test, level II.

PMID- 29443859
TI  - Overresuscitation with plasma is associated with sustained fibrinolysis shutdown
      and death in pediatric traumatic brain injury.
AB  - BACKGROUND: Elevated International Normalized Ratio (INR) is a marker of poor
      outcome but not necessarily bleeding or clinical coagulopathy in injured
      children. Conversely, children with traumatic brain injury (TBI) tend to be
      hypercoagulable based on rapid thromboelastography (rTEG) parameters. Many
      clinicians continue to utilize INR as a treatment target. METHODS: Prospective
      observational study of severely injured children age < 18 with rTEG on arrival
      and daily thereafter for up to 7 days. Standard rTEG definitions of
      hyperfibrinolysis (LY30 >= 3), fibrinolysis shutdown (SD) (LY30 <= 0.8), and
      normal (LY30 = 0.9-2.9) were applied. The first 24-hour blood product transfusion
      volumes were documented. Abbreviated Injury Scale score >= 3 defined severe TBI.
      Sustained SD was defined as two consecutive rTEG with SD and no subsequent
      normalization. Primary outcomes were death and functional disability, based on
      functional independence measure score assessed at discharge. RESULTS: One hundred
      one patients were included: median age, 8 years (interquartile range, 4-12
      years); Injury Severity Score, 25 (16-30); 72% blunt mechanism; 47% severe TBI;
      16% mortality; 45% discharge disability. Neither total volume nor any single
      product volume transfused (mL/kg; all p > 0.1) differed between TBI and non-TBI
      groups. On univariate analysis, transfusion of packed red blood cells (p =
      0.016), plasma (p < 0.001), and platelets (p = 0.006) were associated with
      sustained SD; however, in a regression model that included all products (mL/kg)
      and controlled for severe TBI (head Abbreviated Injury Scale score >= 3),
      admission INR, polytrauma, and clinical bleeding, only plasma remained an
      independent predictor of sustained SD (odds ratio, 1.17; p = 0.031). Patients
      with both severe TBI and plasma transfusion had 100% sustained SD, 75% mortality,
      and 100% disability in survivors. Admission INR was elevated in TBI patients, but
      did not correlate with rTEG activated clotting time (p = NS) and was associated
      with sustained SD (p = 0.006). CONCLUSION: Plasma transfusion is independently
      associated with sustained fibrinolysis SD. Severe TBI is also associated with
      sustained SD; the combined effect of plasma transfusion and severe TBI is
      associated with extremely poor prognosis. Plasma transfusion should not be
      targeted to INR thresholds but rather to rTEG activated clotting time and
      clinical bleeding. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level
      III.

PMID- 29443860
TI  - A novel rat model of extremity trauma for prehospital pain management research.
AB  - BACKGROUND: Pain management is important in prehospital care of patients with
      extremity trauma (ET). The goal of this study was to establish a rat model of ET
      for prehospital pain research and validate it using pain behaviors and
      analgesics. METHODS: Rats were anesthetized using isoflurane, and ET was induced
      in one hindlimb via clamping retrofemoral tissues for 30 seconds, followed by
      closed fibula fracture. Rats regained consciousness after ET. Pain responses in
      the injured hindlimb to thermal hyperalgesia (paw withdrawal latency [PWL]),
      mechanical allodynia (paw withdrawal pressure [PWP]), and weight bearing (WB)
      were determined before and 90 minutes after ET. Morphine (2 mg/kg), fentanyl (10
      MUg/kg), sufentanil (1 MUg/kg), ketamine (5 mg/kg), or vehicle (saline) were then
      administered via intravenous (i.v.) injection, followed by PWL, PWP, and WB
      assessments at 10 minutes, 40 minutes, 80 minutes, and 120 minutes after
      analgesia. RESULTS: After ET, PWL, PWP, and WB were significantly decreased by 61
      +/- 4%, 64 +/- 8%, and 65 +/- 4%, respectively, compared with pre-ET values.
      These pain behaviors were maintained for 3 hours to 4 hours. Compared with the
      saline group, opioid analgesics significantly increased PWL for at least 80
      minutes, with sufentanil exhibiting the highest analgesic effect. An increase in
      PWL was only observed at 10 minutes after ketamine. The PWP was transiently
      increased with opioid analgesics for 10 minutes to 40 minutes, but was not
      changed with ketamine. Weight bearing was improved with opioid analgesics for at
      least 2 hours, but only for up to 80 minutes with ketamine. CONCLUSION: Our ET
      model includes long bone fracture and soft tissue injury, but no fixation
      surgery, mimicking prehospital ET. Our model produces acute, steady, and
      reproducible trauma-related pain behaviors, and is clinically relevant regarding
      the pain behaviors and established responses to common analgesics. This model of
      acute pain due to ET is ideal for prehospital pain management research.

PMID- 29443861
TI  - Boerhaave syndrome: Challenges in diagnosis and treatment of the early
      presentation and its complication.

PMID- 29443862
TI  - Red tides: Mass casualty and whole blood at sea.
AB  - BACKGROUND: The U.S. Navy's casualty-receiving ships provide remote damage
      control resuscitation platforms to treat injured combatants deployed afloat and
      ashore. We report a significant mass casualty incident aboard the USS Bataan, and
      the most warm fresh whole blood (WFWB) transfused at sea for traumatic
      hemorrhagic shock since the Vietnam War. METHODS: Casualty-receiving ships have
      robust medical capabilities, including a frozen blood bank with packed red blood
      cells (pRBC) and fresh frozen plasma (FFP). The blood supply can be augmented
      with WFWB collected from a "walking blood bank." RESULTS: Following a helicopter
      crash, six patients were transported by MV-22 Osprey to the USS Bataan. Patient 1
      had a pelvic fracture, was managed with a pelvic binder, and received 4 units of
      pRBC, 2 units of FFP, and 6 units of WFWB. Patient 2, with a comminuted tibia and
      fibula fracture, underwent lower extremity four-compartment fasciotomy, and
      received 4 units of WFWB. Patient 3 underwent several procedures, including left
      anterior thoracotomy, aortic cross-clamping, exploratory laparotomy, small bowel
      resection, and tracheostomy. He received 8 units of pRBC, 8 units of FFP, and 28
      units of WFWB. Patients 4 and 5 had suspected spine injuries and were managed
      nonoperatively. Patient 6, with open tibia and fibula fractures, underwent lower
      extremity four-compartment fasciotomy with tibia external fixation and received 1
      unit of WFWB. All patients survived aeromedical evacuation to a role 4 medical
      facility and subsequent transfer to local hospitals. CONCLUSION: Maritime
      military mass casualty incidents are challenging, but the U.S. Navy's casualty
      receiving ships are ready to perform remote damage control resuscitation at sea.
      Activation of the ship's walking blood bank to transfuse WFWB is essential for
      hemostatic resuscitations afloat. LEVEL OF EVIDENCE: Study type: case series,
      level V.

PMID- 29443863
TI  - Trauma-induced insurance instability: Variation in insurance coverage for
      patients who experience readmission after injury.
AB  - BACKGROUND: Traumatic injuries result in a significant disruption to patients'
      lives, including their ability to work, which may place patients at risk of
      losing insurance coverage. Our objective was to evaluate the impact of injury on
      insurance status. We hypothesized that trauma patients with ongoing health needs
      experience changes in coverage. METHODS: We used the Nationwide Readmission
      Database (2013-2014), a nationally representative sample of readmissions in the
      United States. We included patients aged 27 years to 64 years admitted with any
      diagnosis of trauma with at least one readmission within 6 months. Patients on
      Medicare and with missing payer information were excluded. The primary outcome
      was payer status. RESULTS: 57,281 patients met inclusion criteria, 11,006 (19%)
      changed insurance payer at readmission. Of these, 21% (n = 2,288) became
      uninsured, 25% (n = 2,773) gained coverage, and 54% (n = 5,945) switched
      insurance. Medicaid and Medicare gained the largest fraction of patients (from
      16% to 30% and 0% to 18%, respectively), with a decrease in private payer
      coverage (37% to 17%). In multivariate analysis, patients who were younger (27-35
      years vs. 56-64 years; odds ratio [OR], 1.30; p < 0.001); lived in a zip code
      with average income in the lowest quartile (vs. the highest quartile; OR, 1.37; p
      < 0.001); and had three or more comorbidities (vs. none; OR, 1.61; p < 0.001)
      were more likely to experience a change in insurance. CONCLUSION: Approximately
      one fifth of trauma patients who are readmitted within 6 months of their injury
      experience a change in insurance coverage. Most switch between insurers, but
      nearly a quarter lose their insurance. The government adopts a large fraction of
      these patients, indicating a growing reliance on government programs like
      Medicaid. Trauma patients face challenges after injury, and a change in insurance
      may add to this burden. Future policy and quality improvement initiatives should
      consider addressing this challenge. LEVEL OF EVIDENCE: Epidemiologic, level III.

PMID- 29443864
TI  - Past and present role of extracorporeal membrane oxygenation in combat casualty
      care: How far will we go?
AB  - Advanced extracorporeal therapies have been successfully applied in the austere
      environment of combat casualty care over the previous decade. In this review, we
      describe the historic underpinnings of extracorporeal membrane oxygenation,
      review the recent experience with both partial and full lung support during
      combat operations, and critically assess both the current status of the
      Department of Defense extracorporeal membrane oxygenation program and the way
      forward to establish long-range lung rescue therapy as a routine capability for
      combat casualty care.

PMID- 29443865
TI  - Prediction of traumatic carotid-cavernous sinus fistula via noncontrast computed
      tomography by fracture pattern and abnormality of venous system: Methodological
      issues on prediction studies.

PMID- 29443866
TI  - Factors associated with trauma patients' length of stay at Role 2 facilities in
      Afghanistan, October 2009 to September 2014.
AB  - BACKGROUND: Understanding patients' length of stay at far-forward Role 2 surgical
      units may help to determine support needs, stabilization requirements,
      predeployment training, and necessity of increased care capability before or
      during transport to a higher level of care. The objectives of this study were to
      (1) evaluate the amount of time patients spent at Role 2 and (2) determine the
      factors associated with trauma patients' length of stay at Role 2. METHODS: We
      conducted a secondary data analysis of the Joint Trauma System Role 2 Database.
      Logistic regression was used to determine factors associated with extended length
      of stay at Role 2. RESULTS: There were 7,912 study patients, and the overall
      median (interquartile range) amount of time patients spent at Role 2 was 2.5 (1.2
      5.5) hours. The adjusted odds ratio (aOR) of extended stay for civilian/other
      forces and non-US military patients were 1.2 (95% confidence interval [CI], 1.0
      1.4) and 1.4 (95% CI, 1.2-1.7) times higher as compared with US military
      patients, respectively. The aOR of extended stay were higher for patients who
      received blood transfusions (aOR, 1.4; 95% CI, 1.2-1.6), surgical procedures
      (aOR, 1.6; 95% CI, 1.4-1.8), or did not use a tourniquet (aOR, 1.2; 95% CI, 1.0
      1.5). As compared with those injured by an explosion, the adjusted odds of
      extended stay were 1.2 (95% CI, 1.0-1.4) times higher for patients injured by
      another mechanism. The odds of extended stay were lower (aOR, 0.3; 95% CI, 0.2
      0.5) for patients who died and higher (aOR, 1.4; 95% CI, 1.2-1.6) for transferred
      patients as compared with patients who returned to duty. CONCLUSION: In this
      study, interventions, patient affiliation, discharge status, and injury mechanism
      were associated with length of stay at Role 2. Our study results will help inform
      training and current Role 2 logistic and personnel support needs. LEVEL OF
      EVIDENCE: Prognostic, level III.

PMID- 29443867
TI  - Effects of Whole-Body Vibration Versus Pilates Exercise on Bone Mineral Density
      in Postmenopausal Women: A Randomized and Controlled Clinical Trial.
AB  - BACKGROUND AND PURPOSE: Decreased bone mineral density (BMD) is a common
      condition in postmenopausal women that can be managed with impact activities.
      Among the activities studied are the whole-body vibration (WBV) and muscle
      strengthening exercises. The purpose of this study was to compare the effects of
      WBV versus Pilates exercise on BMD in postmenopausal women. METHODS: In this
      study, 51 postmenopausal women were randomized into 3 groups: vibration (n = 17),
      Pilates (n = 17), and control (n = 17). Outcomes were the areal bone mineral
      density (aBMD) (lumbar spine, femoral neck, total hip, trochanter,
      intertrochanter, and ward's area) assessed by dual-energy x-ray absorptiometry at
      baseline and follow-up. The interventions were performed 3 times a week for 6
      months, totaling 78 sessions. The analysis was performed with intention-to-treat
      and covariance analyses adjusted for baseline outcomes. RESULTS: After 6 months,
      96.1% of the participants completed the follow-up. The analyses demonstrated
      significant mean between-group differences in favor of the interventions:
      vibration versus control, for the aBMD of the lumbar spine (0.014 g/cm; 95%
      confidence interval [CI], 0.006-0.022; P= .018, d = 1.21) and trochanter (0.018
      g/cm; 95% CI, 0.006-0.030; P = .012, d = 1.03); and Pilates versus control, for
      the aBMD of the lumbar spine (0.016 g/cm; 95% CI, 0.007-0.025; P = .008, d =
      1.15) and trochanter (0.020 g/cm; 95% CI, 0.010-0.031; P = .005, d = 1.28).
      CONCLUSION: In postmenopausal women, 3 weekly sessions of WBV or Pilates
      administered for 6 months provided an equal effect on BMD.

PMID- 29443868
TI  - Circular Array of Magnetic Sensors for Current Measurement: Analysis for Error
      Caused by Position of Conductor.
AB  - This paper analyzes the measurement error, caused by the position of the current
      carrying conductor, of a circular array of magnetic sensors for current
      measurement. The circular array of magnetic sensors is an effective approach for
      AC or DC non-contact measurement, as it is low-cost, light-weight, has a large
      linear range, wide bandwidth, and low noise. Especially, it has been claimed that
      such structure has excellent reduction ability for errors caused by the position
      of the current-carrying conductor, crosstalk current interference, shape of the
      conduction cross-section, and the Earth's magnetic field. However, the positions
      of the current-carrying conductor-including un-centeredness and un
      perpendicularity-have not been analyzed in detail until now. In this paper, for
      the purpose of having minimum measurement error, a theoretical analysis has been
      proposed based on vector inner and exterior product. In the presented
      mathematical model of relative error, the un-center offset distance, the un
      perpendicular angle, the radius of the circle, and the number of magnetic sensors
      are expressed in one equation. The comparison of the relative error caused by the
      position of the current-carrying conductor between four and eight sensors is
      conducted. Tunnel magnetoresistance (TMR) sensors are used in the experimental
      prototype to verify the mathematical model. The analysis results can be the
      reference to design the details of the circular array of magnetic sensors for
      current measurement in practical situations.

PMID- 29443869
TI  - Comparison of Toxic Metal Distribution Characteristics and Health Risk between
      Cultured and Wild Fish Captured from Honghu City, China.
AB  - Honghu Lake, which listed in the "Ramsar Convention", is the seventh largest
      freshwater lake in China and is regarded as one of the biggest freshwater product
      output areas in China. The toxic element distribution in cultured and wild fish
      and the corresponding health risks through fish consumption from Honghu area were
      investigated. The mean concentration in the muscle of cultured and wild fish
      (Carassius auratus and Ctenopharyngodon idellus) decreased in the order: Zn
      (18.94) > Cu (0.8489) > Cr (0.2840) > Pb (0.2052) and Zn (16.30) > Cr (1.947) >
      Cu (0.4166) > Pb (0.0525) > Cd (0.0060) (mean; mg/kg, wet weight). Scales (Multi
      factor pollution index (MPI) = 3.342) and the liver (MPI = 1.276) were regarded
      as the main accumulation tissues for cultured fish, and the bladder (MPI = 0.640)
      and intestine (MPI = 0.477) were regarded as the main accumulation tissues for
      wild fish. There were no obvious health risks associated with the consumption of
      cultured and wild fish based on the calculated results of the target hazard
      quotient (THQ), carcinogenic risk (CR), and estimated weekly intake (EWI). Pb and
      Cr were recognized as the major health risk contributors for inhabitants through
      wild and cultured fish consumption. Cultured fish had a greater health risk than
      wild fish based on the calculation results of THQ and CR. Muscle consumption
      resulted in more health risks than mixed edible tissues for cultured fish, but
      for wild fish, the conclusion was the opposite. Mixed fish (cultured:wild = 1:1)
      muscle consumption had relatively lower risks than the consumption of cultured or
      wild fish muscle separately. Consuming no more than 465 g/day (wet wt) of
      cultured fish muscle, 68 g/day (wet wt) of wild fish muscle, 452 g/day (wet wt)
      of mixed cultured fish edible tissues or 186 g/day (wet wt) of mixed wild fish
      edible tissues from the Honghu area can assure human health.

PMID- 29443870
TI  - A Point Mutation V419L in the Sodium Channel Gene from Natural Populations of
      Aedes aegypti Is Involved in Resistance to lambda-Cyhalothrin in Colombia.
AB  - Resistance to pyrethroids in mosquitoes is mainly caused by target site
      insensitivity known as knockdown resistance (kdr). In this work, we examined the
      point mutations present in portions of domains I, II, III, and IV of the sodium
      channel gene in Aedes aegypti mosquitoes from three Colombian municipalities. A
      partial region coding for the sodium channel gene from resistant mosquitoes was
      sequenced, and a simple allele-specific PCR-based assay (AS-PCR) was used to
      analyze mutations at the population level. The previously reported mutations,
      V1016I and F1534C, were found with frequencies ranging from 0.04 to 0.41, and
      0.56 to 0.71, respectively, in the three cities. Moreover, a novel mutation, at
      419 codon (V419L), was found in Ae. aegypti populations from Bello, Riohacha and
      Villavicencio cities with allelic frequencies of 0.06, 0.36, and 0.46,
      respectively. Interestingly, the insecticide susceptibility assays showed that
      mosquitoes from Bello were susceptible to lambda-cyhalothrin pyrethroid whilst
      those from Riohacha and Villavicencio were resistant. A positive association
      between V419L and V1016I mutations with lambda-cyhalothrin resistance was
      established in Riohacha and Villavicencio. The frequency of the F1534C was high
      in the three populations, suggesting that this mutation could be conferring
      resistance to insecticides other than lambda-cyhalothrin, particularly type I
      pyrethroids. Further studies are required to confirm this hypothesis.

PMID- 29443871
TI  - The Development and Test of a Sensor for Measurement of the Working Level of Gas
      Liquid Two-Phase Flow in a Coalbed Methane Wellbore Annulus.
AB  - Coalbed methane (CBM) is one kind of clean-burning gas and has been valued as a
      new form of energy that will be used widely in the near future. When producing
      CBM, the working level within a CBM wellbore annulus needs to be monitored to
      dynamically adjust the gas drainage and extraction processes. However, the
      existing method of measuring the working level does not meet the needs of
      accurate adjustment, so we designed a new sensor for this purpose. The principle
      of our sensor is a liquid pressure formula, i.e., the sensor monitors the two
      phase flow patterns and obtains the mean density of the two-phase flow according
      to the pattern recognition result in the first step, and then combines the
      pressure data of the working level to calculate the working level using the
      liquid pressure formula. The sensor was tested in both the lab and on site, and
      the tests showed that the sensor's error was +/-8% and that the sensor could
      function well in practical conditions and remain stable in the long term.

PMID- 29443872
TI  - AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis.
AB  - Melanocytes are specialized cells that generate unique organelles called
      melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and
      melanocyte pigmentation require the transport and delivery of melanin
      synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from
      endosomes to maturing melanosomes. Among the proteins controlling endosome
      melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting
      and trafficking of TYRP1 to melanosomes. We identify here beta1-adaptin AP-1
      subunit-derived peptides of 5 amino acids that block the interaction of KIF13A
      with AP-1 in cells. Incubating these peptides with human MNT-1 cells or 3D
      reconstructed pigmented epidermis decreases pigmentation by impacting the
      maturation of melanosomes in fully pigmented organelles. This study highlights
      that peptides targeting the intracellular trafficking of melanocytes are
      candidate molecules to tune pigmentation in health and disease.

PMID- 29443873
TI  - A Ketogenic Formula Prevents Tumor Progression and Cancer Cachexia by Attenuating
      Systemic Inflammation in Colon 26 Tumor-Bearing Mice.
AB  - Low-carbohydrate, high-fat diets (ketogenic diets) might prevent tumor
      progression and could be used as supportive therapy; however, few studies have
      addressed the effect of such diets on colorectal cancer. An infant formula with a
      ketogenic composition (ketogenic formula; KF) is used to treat patients with
      refractory epilepsy. We investigated the effect of KF on cancer and cancer
      cachexia in colon tumor-bearing mice. Mice were randomized into normal (NR),
      tumor-bearing (TB), and ketogenic formula (KF) groups. Colon 26 cells were
      inoculated subcutaneously into TB and KF mice. The NR and TB groups received a
      standard diet, and the KF mice received KF ad libitum. KF mice preserved their
      body, muscle, and carcass weights. Tumor weight and plasma IL-6 levels were
      significantly lower in KF mice than in TB mice. In the KF group, energy intake
      was significantly higher than that in the other two groups. Blood ketone body
      concentrations in KF mice were significantly elevated, and there was a
      significant negative correlation between blood ketone body concentration and
      tumor weight. Therefore, KF may suppress the progression of cancer and the
      accompanying systemic inflammation without adverse effects on weight gain, or
      muscle mass, which might help to prevent cancer cachexia.

PMID- 29443874
TI  - Dental Application of Natural Products.
AB  - This review article summarizes the recent progress in dental applications of
      natural products. Catechin gel showed selective antimicrobial activity, whereas
      the alkaline extract of various plant species rich in lignin carbohydrate complex
      (LCC) showed much higher antiviral activity than lower molecular weight
      polyphenols. Mouthwash with the alkaline extract of a plant classified as OTC
      effectively reduced halitosis. Unexpectedly, many polyphenolic compounds purified
      from the natural kingdom showed much lower tumor-specificity against human oral
      squamous cell lines as compared with antitumor agents, although they showed
      apoptosis-inducing activity. The alkaline extract of bamboo leaf, which exerted
      various common biological activities with LCC, showed osteogenic activity by
      stimulating differentiation toward osteoblasts while inhibiting differentiation
      toward osteoclasts. LCC enhanced the dectin-2 mRNA expression in macrophages,
      whereas glucan showed anti-osteoblastic action via dectin-1. These data suggest
      that natural products exert their biological activity by interacting with these
      molecules.

PMID- 29443875
TI  - On the Reaction Mechanism of the 3,4-Dimethoxybenzaldehyde Formation from 1
      (3',4'-Dimethoxyphenyl)Propene.
AB  - Lignin peroxidase (LiP) is an important enzyme for degrading aromatic
      hydrocarbons not only in nature but also in industry. In the presence of H2O2,
      this enzyme can easily decompose lignin and analogue compounds under mild
      conditions. In this reaction mechanism, LiP catalyzes the C-C cleavage of a
      propenyl side chain, being able to produce veratraldehyde (VAD) from 1-(3',4'
      dimethoxyphenyl) propene (DMPP). One of the few and complete proposed mechanisms
      includes several non-enzymatic reactions. In this study, we performed a
      computational study to gain insight about the non-enzymatic steps involved in the
      reaction mechanism of VAD formation from DMPP using LiP as a catalyst. A kinetic
      characterization of the reaction using the reaction force and the reaction force
      constant concepts within the density functional theory (DFT) framework is
      proposed. All theoretical calculations for the reaction pathway were performed
      using the Minnesota Global Hybrid functional M06-2X and a 6-31++G(d,p) basis set.
      The complete reaction comprises seven steps (five steps not including LiP as a
      catalyst), which include radical species formation, bond transformation, water
      and oxygen addition, atom reordering, and deacetylation. The overall mechanism is
      an endothermic process with mixed activation energies depending on the four
      transition states. These results are the first attempt to fully understand the
      catalytic role of LiP in the degradation of lignin and its aromatic derivative
      compounds in terms of the electronic structure methods and future hybrid
      calculation approaches that we have recently been performing.

PMID- 29443876
TI  - Analysing the Zenith Tropospheric Delay Estimates in On-line Precise Point
      Positioning (PPP) Services and PPP Software Packages.
AB  - As Global Navigation Satellite System (GNSS) signals travel through the
      troposphere, a tropospheric delay occurs due to a change in the refractive index
      of the medium. The Precise Point Positioning (PPP) technique can achieve
      centimeter/millimeter positioning accuracy with only one GNSS receiver. The
      Zenith Tropospheric Delay (ZTD) is estimated alongside with the position unknowns
      in PPP. Estimated ZTD can be very useful for meteorological applications, an
      example is the estimation of water vapor content in the atmosphere from the
      estimated ZTD. PPP is implemented with different algorithms and models in online
      services and software packages. In this study, a performance assessment with
      analysis of ZTD estimates from three PPP online services and three software
      packages is presented. The main contribution of this paper is to show the
      accuracy of ZTD estimation achievable in PPP. The analysis also provides the GNSS
      users and researchers the insight of the processing algorithm dependence and
      impact on PPP ZTD estimation. Observation data of eight whole days from a total
      of nine International GNSS Service (IGS) tracking stations spread in the northern
      hemisphere, the equatorial region and the southern hemisphere is used in this
      analysis. The PPP ZTD estimates are compared with the ZTD obtained from the IGS
      tropospheric product of the same days. The estimates of two of the three online
      PPP services show good agreement (<1 cm) with the IGS ZTD values at the northern
      and southern hemisphere stations. The results also show that the online PPP
      services perform better than the selected PPP software packages at all stations.

PMID- 29443877
TI  - Drugs and Mental Health Problems among the Roma: Protective Factors Promoted by
      the Iglesia Evangelica Filadelfia.
AB  - Background: High incidences of drug consumption and mental health problems are
      found among the Roma population in Spain, a reality that remains understudied.
      Past studies have indicated the positive role played by the Iglesia Evangelica
      Filadelfia (IEF) in promoting rehabilitation and prevention of these practices.
      Objective: In this article, authors analyze in which ways the IEF favors
      processes of drug rehabilitation and mental health recovery as well as the
      prevention of these problems among its Roma members. Methods: A communicative
      qualitative approach was developed. It was communicative because new knowledge
      was created by dialogically contrasting the existing state of the art with study
      participants. It was qualitative because everyday life stories were collected,
      gathering the experiences, perceptions and interpretations of Roma people who are
      actively involved in three different IEF churches based in Barcelona. Results:
      This article identifies these protective factors: anti-drug discourse, a
      supportive environment, new social relations, role model status, the promotion of
      interactions, the revaluation of oneself, spiritual activities and the
      improvement of the feeling of belonging and the creation of meaning. Conclusion:
      The present research contributes new evidence to the current understanding of the
      role played by the IEF in improving Roma health status and how the identified
      protective factors can contribute to rehabilitation and recovery from such
      problems in other contexts.

PMID- 29443878
TI  - Skeletal Muscle Pathophysiology: The Emerging Role of Spermine Oxidase and
      Spermidine.
AB  - Skeletal muscle comprises approximately 40% of the total body mass. Preserving
      muscle health and function is essential for the entire body in order to
      counteract chronic diseases such as type II diabetes, cardiovascular diseases,
      and cancer. Prolonged physical inactivity, particularly among the elderly, causes
      muscle atrophy, a pathological state with adverse outcomes such as poor quality
      of life, physical disability, and high mortality. In murine skeletal muscle C2C12
      cells, increased expression of the spermine oxidase (SMOX) enzyme has been found
      during cell differentiation. Notably, SMOX overexpression increases muscle fiber
      size, while SMOX reduction was enough to induce muscle atrophy in multiple murine
      models. Of note, the SMOX reaction product spermidine appears to be involved in
      skeletal muscle atrophy/hypertrophy. It is effective in reactivating autophagy,
      ameliorating the myopathic defects of collagen VI-null mice. Moreover, spermidine
      treatment, if combined with exercise, can affect D-gal-induced aging-related
      skeletal muscle atrophy. This review hypothesizes a role for SMOX during skeletal
      muscle differentiation and outlines its role and that of spermidine in muscle
      atrophy. The identification of new molecular pathways involved in the maintenance
      of skeletal muscle health could be beneficial in developing novel therapeutic
      lead compounds to treat muscle atrophy.

PMID- 29443880
TI  - Magnetic Nanoparticles Interact and Pass an In Vitro Co-Culture Blood-Placenta
      Barrier Model.
AB  - Magnetic nanoparticles are interesting tools for biomedicine. Before application,
      critical prerequisites have to be fulfilled. An important issue is the contact
      and interaction with biological barriers such as the blood-placenta barrier. In
      order to study these processes in detail, suitable in vitro models are needed.
      For that purpose a blood-placenta barrier model based on the trophoblast-like
      cell line BeWo and primary placenta-derived pericytes was established. This model
      was characterized by molecular permeability, transepithelial electrical
      resistance and cell-cell-contact markers. Superparamagnetic iron oxide
      nanoparticles (SPIONs) with cationic, anionic or neutral surface charge were
      applied. The localization of the nanoparticles within the cells was illustrated
      by histochemistry. The time-dependent passage of the nanoparticles through the
      BeWo/pericyte barrier was measured by magnetic particle spectroscopy and atomic
      absorption spectroscopy. Cationically coated SPIONs exhibited the most extensive
      interaction with the BeWo cells and remained primarily in the BeWo/pericyte cell
      layer. In contrast, SPIONs with neutral and anionic surface charge were able to
      pass the cell layer to a higher extent and could be detected beyond the barrier
      after 24 h. This study showed that the mode of SPION interaction with and passage
      through the in vitro blood-placenta barrier model depends on the surface charge
      and the duration of treatment.

PMID- 29443879
TI  - Comparison of Rumen and Manure Microbiomes and Implications for the Inoculation
      of Anaerobic Digesters.
AB  - Cattle manure is frequently used as an inoculum for the start-up of agricultural
      biogas plants or as a co-substrate in the anaerobic digestion of lignocellulosic
      feedstock. Ruminal microbiota are considered to be effective plant fiber
      degraders, but the microbes contained in manure do not necessarily reflect the
      rumen microbiome. The aim of this study was to compare the microbial community
      composition of cow rumen and manure with respect to plant fiber-digesting
      microbes. Bacterial and methanogenic communities of rumen and manure samples were
      examined by 454 amplicon sequencing of bacterial 16S rRNA genes and mcrA genes,
      respectively. Rumen fluid samples were dominated by Prevotellaceae (29%), whereas
      Ruminococcaceae was the most abundant family in the manure samples (31%).
      Fibrobacteraceae (12%) and Bacteroidaceae (13%) were the second most abundant
      families in rumen fluid and manure, respectively. The high abundances of fiber
      degrading bacteria belonging to Prevotellaceae and Fibrobacteraceae might explain
      the better performance of anaerobic digesters inoculated with rumen fluid.
      Members of the genus Methanobrevibacter were the predominant methanogens in the
      rumen fluid, whereas methanogenic communities of the manure samples were
      dominated by the candidate genus Methanoplasma. Our results suggest that
      inoculation or bioaugmentation with fiber-digesting rumen microbiota can enhance
      the anaerobic digestion of lignocellulosic biomass.

PMID- 29443881
TI  - GWAS Uncovers Differential Genetic Bases for Drought and Salt Tolerances in
      Sesame at the Germination Stage.
AB  - Sesame has great potential as an industrial crop but its production is challenged
      by drought and salt stresses. To unravel the genetic variants leading to salinity
      and drought tolerances at the germination stage, genome-wide association studies
      of stress tolerance indexes related to NaCl-salt and polyethylene glycol-drought
      induced stresses were performed with a diversity panel of 490 sesame accessions.
      An extensive variation was observed for drought and salt responses in the
      population and most of the accessions were moderately tolerant to both stresses.
      A total of 132 and 120 significant Single Nucleotide Polymorphisms (SNPs)
      resolved to nine and 15 Quantitative trait loci (QTLs) were detected for drought
      and salt stresses, respectively. Only two common QTLs for drought and salt
      responses were found located on linkage groups 5 and 7, respectively. This
      indicates that the genetic bases for drought and salt responses in sesame are
      different. A total of 13 and 27 potential candidate genes were uncovered for
      drought and salt tolerance indexes, respectively, encoding transcription factors,
      antioxidative enzymes, osmoprotectants and involved in hormonal biosynthesis,
      signal transduction or ion sequestration. The identified SNPs and potential
      candidate genes represent valuable resources for future functional
      characterization towards the enhancement of sesame cultivars for drought and salt
      tolerances.

PMID- 29443882
TI  - Effects of TROL Presequence Mutagenesis on Its Import and Dual Localization in
      Chloroplasts.
AB  - Thylakoid rhodanase-like protein (TROL) is involved in the final step of
      photosynthetic electron transport from ferredoxin to ferredoxin: NADP+
      oxidoreductase (FNR). TROL is located in two distinct chloroplast compartments-in
      the inner envelope of chloroplasts, in its precursor form; and in the thylakoid
      membranes, in its fully processed form. Its role in the inner envelope, as well
      as the determinants for its differential localization, have not been resolved
      yet. In this work we created six N-terminal amino acid substitutions surrounding
      the predicted processing site in the presequence of TROL in order to obtain a
      construct whose import is affected or localization limited to a single
      intrachloroplastic site. By using in vitro transcription and translation and
      subsequent protein import methods, we found that a single amino acid exchange in
      the presequence, Ala67 to Ile67 interferes with processing in the stroma and
      directs the whole pool of in vitro translated TROL to the inner envelope of
      chloroplasts. This result opens up the possibility of studying the role of TROL
      in the chloroplast inner envelope as well as possible consequence/s of its
      absence from the thylakoids.

PMID- 29443883
TI  - Synthesis, Characterization, and Computational Modeling of N-(1
      Ethoxyvinyl)pyridinium Triflates, an Unusual Class of Pyridinium Salts.
AB  - N-Substituted pyridinium salts constitute one of the most valuable reagent
      classes in organic synthesis, due to their versatility and ease of use. Herein we
      report a preliminary synthesis and detailed structural analysis of several N-(1
      ethoxyvinyl)pyridinium triflates, an unusual class of pyridinium salts with
      potentially broad use as a reagent in organic synthesis. Treatment of pyridines
      with trifluoromethane sulfonic acid and ethoxyacetylene generates stable,
      isolable adducts which have been extensively characterized, due to their novelty.
      Three-dimensional structural stability is perpetuated by an array of C-H***O
      hydrogen bonds involving oxygen atoms from the -SO3 groups of the triflate anion,
      and hydrogen atoms from the aromatic ring and vinyl group of the pyridinium
      cation. Predictions from density functional theory calculations of the energy
      landscape for rotation about the exocyclic C-N bond of 2-chloro-1-(1
      ethoxyvinyl)pyridine-1-ium trifluoromethanesulfonate (7) and 1-(1
      ethoxyvinyl)pyridine-1-ium trifluoromethanesulfonate (16) are also reported.
      Notably, the predicted global energy minimum of 7 was nearly identical to that
      found within the crystal structure.

PMID- 29443884
TI  - Linear Regression QSAR Models for Polo-Like Kinase-1 Inhibitors.
AB  - A structurally diverse dataset of 530 polo-like kinase-1 (PLK1) inhibitors is
      compiled from the ChEMBL database and studied by means of a conformation
      independent quantitative structure-activity relationship (QSAR) approach. A large
      number (26,761) of molecular descriptors are explored with the main intention of
      capturing the most relevant structural characteristics affecting the bioactivity.
      The structural descriptors are derived with different freeware, such as PaDEL,
      Mold2, and QuBiLs-MAS; such descriptor software complements each other and
      improves the QSAR results. The best multivariable linear regression models are
      found with the replacement method variable subset selection technique. The
      balanced subsets method partitions the dataset into training, validation, and
      test sets. It is found that the proposed linear QSAR model improves previously
      reported models by leading to a simpler alternative structure-activity
      relationship.

PMID- 29443885
TI  - Genome Size Diversity and Its Impact on the Evolution of Land Plants.
AB  - Genome size is a biodiversity trait that shows staggering diversity across
      eukaryotes, varying over 64,000-fold. Of all major taxonomic groups, land plants
      stand out due to their staggering genome size diversity, ranging ca. 2400-fold.
      As our understanding of the implications and significance of this remarkable
      genome size diversity in land plants grows, it is becoming increasingly evident
      that this trait plays not only an important role in shaping the evolution of
      plant genomes, but also in influencing plant community assemblages at the
      ecosystem level. Recent advances and improvements in novel sequencing
      technologies, as well as analytical tools, make it possible to gain critical
      insights into the genomic and epigenetic mechanisms underpinning genome size
      changes. In this review we provide an overview of our current understanding of
      genome size diversity across the different land plant groups, its implications on
      the biology of the genome and what future directions need to be addressed to fill
      key knowledge gaps.

PMID- 29443886
TI  - Antibacterial Peptides in Dermatology-Strategies for Evaluation of Allergic
      Potential.
AB  - During recent decades, the market for peptide-based drugs, including
      antimicrobial peptides, has vastly extended and evolved. These drugs can be
      useful in treatment of various types of disorders, e.g., cancer, autoimmune
      diseases, infections, and non-healing wounds. Although peptides are less
      immunogenic than other biologic therapeutics, they can still induce immune
      responses and cause allergies. It is important to evaluate the immunogenic and
      allergic potential of peptides before they are forwarded to the expensive stages
      of clinical trials. The process of the evaluation of immunogenicity and
      cytotoxicity is complicated, as in vitro models and bioinformatics tools cannot
      fully simulate situations in the clinic. Nevertheless, several potentially
      promising tests for the preclinical evaluation of peptide drugs have been
      implemented (e.g., cytotoxicity assays, the basophil activation test, and
      lymphocyte activation assays). In this review, we focus on strategies for
      evaluation of the allergic potential of peptide-based therapeutics.

PMID- 29443887
TI  - Impact of Mutations in the Hemagglutinin of H10N7 Viruses Isolated from Seals on
      Virus Replication in Avian and Human Cells.
AB  - Wild birds are the reservoir for low-pathogenic avian influenza viruses, which
      are frequently transmitted to domestic birds and occasionally to mammals. In
      2014, an H10N7 virus caused severe mortality in harbor seals in northeastern
      Europe. Although the hemagglutinin (HA) of this virus was closely related to H10
      of avian H10N4 virus, it possessed unique nonsynonymous mutations, particularly
      in the HA1 subunit in or adjacent to the receptor binding domain and proteolytic
      cleavage site. Here, the impact of these mutations on virus replication was
      studied in vitro. Using reverse genetics, an avian H10N4 virus was cloned, and
      nine recombinant viruses carrying one of eight unique mutations or the complete
      HA from the seal virus were rescued. Receptor binding affinity, replication in
      avian and mammalian cell cultures, cell-to-cell spread, and HA cleavability of
      these recombinant viruses were studied. Results show that wild-type recombinant
      H10N4 virus has high affinity to avian-type sialic acid receptors and no affinity
      to mammalian-type receptors. The H10N7 virus exhibits dual receptor binding
      affinity. Interestingly, Q220L (H10 numbering) in the rim of the receptor binding
      pocket increased the affinity of the H10N4 virus to mammal-type receptors and
      completely abolished the affinity to avian-type receptors. No remarkable
      differences in cell-to-cell spread or HA cleavability were observed. All viruses,
      including the wild-type H10N7 virus, replicated at higher levels in chicken cells
      than in human cells. These results indicate that H10N7 acquired adaptive
      mutations (e.g., Q220L) to enhance replication in mammals and retained
      replication efficiency in the original avian host.

PMID- 29443888
TI  - Assessing the Potential for Rooftop Rainwater Harvesting from Large Public
      Institutions.
AB  - As in many other cities, urbanization coupled with population growth worsens the
      water supply problem of Addis Ababa, Ethiopia, with a water supply deficit of 41%
      in 2016. To investigate the potential contribution of rooftop rainwater
      harvesting (RWH) from large public institutions, 320 such institutions were
      selected and grouped into 11 categories, from which 25-30% representative 588
      rooftops were digitalized and the potential RWH volume computed based on a ten
      year rainfall dataset. When comparing the resulting RWH potential with the water
      consumption, up to 2.3% of the annual, potable water supply can be provided. If
      reused only within one's own institution, the self-sufficiency varies from 0.9 to
      649%. Non-uniform rainfall patterns add uncertainty to these numbers, since the
      size of the storage tank becomes critical for coverage in the dry season from
      October to May. Despite the low replacement potential at the city level, RWH from
      large institutions will enable a significant volume of potable water to be
      transferred to localities critically suffering from water shortage. Further,
      large institutions may demonstrate how RWH can be practiced, thus acting as a
      frontrunner for the dissemination of RWH to other types of rooftops. To narrow
      the water supply gap, considering rooftop RWH as an alternative water supply
      source is recommended. However, the present study assumed that financial
      constraints to install large sized storage tanks are considered as a possible
      challenge. Thus, future research is needed to investigate the cost-benefit
      balance along with the invention of a cheap storage tank as they may affect the
      potential contribution of RWH from rooftops.

PMID- 29443890
TI  - Embedded Disposable Functionalized Electrochemical Biosensor with a 3D-Printed
      Flow Cell for Detection of Hepatic Oval Cells (HOCs).
AB  - Hepatic oval cells (HOCs) are considered the progeny of the intrahepatic stem
      cells that are found in a small population in the liver after hepatocyte
      proliferation is inhibited. Due to their small number, isolation and capture of
      these cells constitute a challenging task for immunosensor technology. This work
      describes the development of a 3D-printed continuous flow system and exploits
      disposable screen-printed electrodes for the rapid detection of HOCs that over
      express the OV6 marker on their membrane. Multiwall carbon nanotube (MWCNT)
      electrodes have a chitosan film that serves as a scaffold for the immobilization
      of oval cell marker antibodies (anti-OV6-Ab), which enhance the sensitivity of
      the biomarker and makes the designed sensor specific for oval cells. The
      developed sensor can be easily embedded into the 3D-printed flow cell to allow
      cells to be exposed continuously to the functionalized surface. The continuous
      flow is intended to increase capture of most of the target cells in the specimen.
      Contact angle measurements were performed to characterize the nature and quality
      of the modified sensor surface, and electrochemical measurements (cyclic
      voltammetry (CV) and square wave voltammetry (SWV)) were performed to confirm the
      efficiency and selectivity of the fabricated sensor to detect HOCs. The proposed
      method is valuable for capturing rare cells and could provide an effective tool
      for cancer diagnosis and detection.

PMID- 29443889
TI  - Alteration of Epigenetic Regulation by Long Noncoding RNAs in Cancer.
AB  - Long noncoding RNAs (lncRNAs) are important regulators of the epigenetic status
      of the human genome. Besides their participation to normal physiology, lncRNA
      expression and function have been already associated to many diseases, including
      cancer. By interacting with epigenetic regulators and by controlling chromatin
      topology, their misregulation may result in an aberrant regulation of gene
      expression that may contribute to tumorigenesis. Here, we review the functional
      role and mechanisms of action of lncRNAs implicated in the aberrant epigenetic
      regulation that has characterized cancer development and progression.

PMID- 29443891
TI  - Conformational Dynamics and Stability of U-Shaped and S-Shaped Amyloid beta
      Assemblies.
AB  - Alzheimer's disease is the most fatal neurodegenerative disorder characterized by
      the aggregation and deposition of Amyloid beta (Abeta) oligomers in the brain of
      patients. Two principal variants of Abeta exist in humans: Abeta1-40 and Abeta1
      42. The former is the most abundant in the plaques, while the latter is the most
      toxic species and forms fibrils more rapidly. Interestingly, fibrils of Abeta1-40
      peptides can only assume U-shaped conformations while Abeta1-42 can also arrange
      as S-shaped three-stranded chains, as recently discovered. As alterations in
      protein conformational arrangement correlate with cell toxicity and speed of
      disease progression, it is important to characterize, at molecular level, the
      conformational dynamics of amyloid fibrils. In this work, Replica Exchange
      Molecular Dynamics simulations were carried out to compare the conformational
      dynamics of U-shaped and S-shaped Abeta17-42 small fibrils. Our computational
      results provide support for the stability of the recently proposed S-shaped model
      due to the maximized interactions involving the C-terminal residues. On the other
      hand, the U-shaped motif is characterized by significant distortions resulting in
      a more disordered assembly. Outcomes of our work suggest that the molecular
      architecture of the protein aggregates might play a pivotal role in formation and
      conformational stability of the resulting fibrils.

PMID- 29443892
TI  - An Exploration of Underrepresentation of Aboriginal Cancer Patients Attending a
      Regional Radiotherapy Service in Western Australia.
AB  - Travel logistics impede Aboriginal patients' uptake of cancer treatments and is
      one reason for the poorer outcomes of Aboriginal people with cancer. This
      research examined benefits of a newly established rurally based radiotherapy unit
      in southwest Western Australia (WA), and included exploring the experience of
      Aboriginal patients and possible reasons for Aboriginal people's
      underrepresentation in treatment. Semi-structured in-depth interviews with 21
      service providers involved in the treatment and care of people with cancer, and 3
      Aboriginal patients with cancer who undertook radiotherapy at the Service were
      undertaken. Data were subject to thematic analysis involving immersion in the
      data for familiarization, inductive coding, investigator discussion and refining
      of emerging themes and triangulation of patient and provider interviews.
      Aboriginal cancer patients were positive about the treatment and support they had
      received, highlighting the often complex challenges faced by rural Aboriginal
      cancer patients in accessing and maintaining treatment. Service providers offered
      suggestions for small numbers presenting to the Service, including late
      presentation, potential perceptions of cultural insensitivity on the part of
      service providers, out-of-pocket costs and under-ascertainment of Aboriginal
      status. The Service has put in place practices and initiatives to support patient
      health and wellbeing, including making the facility more welcoming towards
      Aboriginal people and ensuring culturally appropriate care.

PMID- 29443893
TI  - A Modular IoT Platform for Real-Time Indoor Air Quality Monitoring.
AB  - The impact of air quality on health and on life comfort is well established. In
      many societies, vulnerable elderly and young populations spend most of their time
      indoors. Therefore, indoor air quality monitoring (IAQM) is of great importance
      to human health. Engineers and researchers are increasingly focusing their
      efforts on the design of real-time IAQM systems using wireless sensor networks.
      This paper presents an end-to-end IAQM system enabling measurement of CO2, CO,
      SO2, NO2, O3, Cl2, ambient temperature, and relative humidity. In IAQM systems,
      remote users usually use a local gateway to connect wireless sensor nodes in a
      given monitoring site to the external world for ubiquitous access of data. In
      this work, the role of the gateway in processing collected air quality data and
      its reliable dissemination to end-users through a web-server is emphasized. A
      mechanism for the backup and the restoration of the collected data in the case of
      Internet outage is presented. The system is adapted to an open-source Internet-of
      Things (IoT) web-server platform, called Emoncms, for live monitoring and long
      term storage of the collected IAQM data. A modular IAQM architecture is adopted,
      which results in a smart scalable system that allows seamless integration of
      various sensing technologies, wireless sensor networks (WSNs) and smart mobile
      standards. The paper gives full hardware and software details of the proposed
      solution. Sample IAQM results collected in various locations are also presented
      to demonstrate the abilities of the system.

PMID- 29443895
TI  - Correction: Shelly Y. Shih; et al.; Applications of Probe Capture Enrichment Next
      Generation Sequencing for Whole Mitochondrial Genome and 426 Nuclear SNPs for
      Forensically Challenging Samples. Genes 2018, 9, 49.
AB  - The authors wish to make the following change to their paper [1][...].

PMID- 29443894
TI  - Justifiability and Animal Research in Health: Can Democratisation Help Resolve
      Difficulties?
AB  - Current animal research ethics frameworks emphasise consequentialist ethics
      through cost-benefit or harm-benefit analysis. However, these ethical frameworks
      along with institutional animal ethics approval processes cannot satisfactorily
      decide when a given potential benefit is outweighed by costs to animals. The
      consequentialist calculus should, theoretically, provide for situations where
      research into a disease or disorder is no longer ethical, but this is difficult
      to determine objectively. Public support for animal research is also falling as
      demand for healthcare is rising. Democratisation of animal research could help
      resolve these tensions through facilitating ethical health consumerism or giving
      the public greater input into deciding the diseases and disorders where animal
      research is justified. Labelling drugs to disclose animal use and providing a
      plain-language summary of the role of animals may help promote public
      understanding and would respect the ethical beliefs of objectors to animal
      research. National animal ethics committees could weigh the competing ethical,
      scientific, and public interests to provide a transparent mandate for animal
      research to occur when it is justifiable and acceptable. Democratic processes can
      impose ethical limits and provide mandates for acceptable research while
      facilitating a regulatory and scientific transition towards medical advances that
      require fewer animals.

PMID- 29443897
TI  - Structured Kernel Subspace Learning for Autonomous Robot Navigation.
AB  - This paper considers two important problems for autonomous robot navigation in a
      dynamic environment, where the goal is to predict pedestrian motion and control a
      robot with the prediction for safe navigation. While there are several methods
      for predicting the motion of a pedestrian and controlling a robot to avoid
      incoming pedestrians, it is still difficult to safely navigate in a dynamic
      environment due to challenges, such as the varying quality and complexity of
      training data with unwanted noises. This paper addresses these challenges
      simultaneously by proposing a robust kernel subspace learning algorithm based on
      the recent advances in nuclear-norm and l 1 -norm minimization. We model the
      motion of a pedestrian and the robot controller using Gaussian processes. The
      proposed method efficiently approximates a kernel matrix used in Gaussian process
      regression by learning low-rank structured matrix (with symmetric positive semi
      definiteness) to find an orthogonal basis, which eliminates the effects of
      erroneous and inconsistent data. Based on structured kernel subspace learning, we
      propose a robust motion model and motion controller for safe navigation in
      dynamic environments. We evaluate the proposed robust kernel learning in various
      tasks, including regression, motion prediction, and motion control problems, and
      demonstrate that the proposed learning-based systems are robust against outliers
      and outperform existing regression and navigation methods.

PMID- 29443896
TI  - Dexamethasone-Mediated Upregulation of Calreticulin Inhibits Primary Human
      Glioblastoma Dispersal Ex Vivo.
AB  - Dispersal of Glioblastoma (GBM) renders localized therapy ineffective and is a
      major cause of recurrence. Previous studies have demonstrated that Dexamethasone
      (Dex), a drug currently used to treat brain tumor-related edema, can also
      significantly reduce dispersal of human primary GBM cells from neurospheres. It
      does so by triggering alpha5 integrin activity, leading to restoration of
      fibronectin matrix assembly (FNMA), increased neurosphere cohesion, and reduction
      of neurosphere dispersal velocity (DV). How Dex specifically activates alpha5
      integrin in these GBM lines is unknown. Several chaperone proteins are known to
      activate integrins, including calreticulin (CALR). We explore the role of CALR as
      a potential mediator of Dex-dependent induction of alpha5 integrin activity in
      primary human GBM cells. We use CALR knock-down and knock-in strategies to
      explore the effects on FNMA, aggregate compaction, and dispersal velocity in
      vitro, as well as dispersal ex vivo on extirpated mouse retina and brain slices.
      We show that Dex increases CALR expression and that siRNA knockdown suppresses
      Dex-mediated FNMA. Overexpression of CALR in GBM cells activates FNMA, increases
      compaction, and decreases DV in vitro and on explants of mouse retina and brain
      slices. Our results define a novel interaction between Dex, CALR, and FNMA as
      inhibitors of GBM dispersal.

PMID- 29443898
TI  - 4-Thiazolidinone Derivatives as MMP Inhibitors in Tissue Damage: Synthesis,
      Biological Evaluation and Docking Studies.
AB  - Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3
      yl)propanamides combining a benzisothiazole and 4-thiazolidinone in one framework
      were designed and synthesized. The aim of the study was to verify their
      effectiveness to affect the inflammatory/oxidative process in which free oxygen
      and nitrite (ROS and RNS) radicals, inflammatory mediators, such as nuclear
      factor kappaB (NF-kappaB), and matrix metalloproteinases (MMPs) are involved.
      Docking studies of all the compounds were performed in order to explore their
      binding mode at the MMP-9 protein. An appreciable anti-inflammatory/potential
      wound healing effects of the tested compounds was highlighted. Derivative 23,
      bearing a 4-carboxyphenyl substituent at C2 of the 4-thiazolidinone ring,
      exhibited the highest activity, being able to inhibit MMP-9 at nanomolar
      level(IC50 = 40 nM).

PMID- 29443900
TI  - Multisensor Analysis of Spectral Dimensionality and Soil Diversity in the Great
      Central Valley of California.
AB  - Planned hyperspectral satellite missions and the decreased revisit time of
      multispectral imaging offer the potential for data fusion to leverage both the
      spectral resolution of hyperspectral sensors and the temporal resolution of
      multispectral constellations. Hyperspectral imagery can also be used to better
      understand fundamental properties of multispectral data. In this analysis, we use
      five flight lines from the Airborne Visible/Infrared Imaging Spectrometer
      (AVIRIS) archive with coincident Landsat 8 acquisitions over a spectrally diverse
      region of California to address the following questions: (1) How much of the
      spectral dimensionality of hyperspectral data is captured in multispectral data?;
      (2) Is the characteristic pyramidal structure of the multispectral feature space
      also present in the low order dimensions of the hyperspectral feature space at
      comparable spatial scales?; (3) How much variability in rock and soil substrate
      endmembers (EMs) present in hyperspectral data is captured by multispectral
      sensors? We find nearly identical partitions of variance, low-order feature space
      topologies, and EM spectra for hyperspectral and multispectral image composites.
      The resulting feature spaces and EMs are also very similar to those from previous
      global multispectral analyses, implying that the fundamental structure of the
      global feature space is present in our relatively small spatial subset of
      California. Finally, we find that the multispectral dataset well represents the
      substrate EM variability present in the study area - despite its inability to
      resolve narrow band absorptions. We observe a tentative but consistent physical
      relationship between the gradation of substrate reflectance in the feature space
      and the gradation of sand versus clay content in the soil classification system.

PMID- 29443899
TI  - Protease-Activated Receptor 4 (PAR4): A Promising Target for Antiplatelet
      Therapy.
AB  - Cardiovascular diseases (CVDs) are currently among the leading causes of death
      worldwide. Platelet aggregation is a key cellular component of arterial thrombi
      and major cause of CVDs. Protease-activated receptors (PARs), including PAR1,
      PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein
      coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute
      to the signaling transduction processes. In association with CVDs, PAR4 not only
      contributes to platelet activation but also is a modulator of cellular responses
      that serve as hallmarks of inflammation. Although several antiplatelet drugs are
      available on the market, they have many side effects that limit their use.
      Emerging evidence shows that PAR4 targeting is a safer strategy for preventing
      thrombosis and consequently may improve the overall cardiac safety profile. Our
      present review summarizes the PAR4 structural characteristics, activation
      mechanism, role in the pathophysiology of diseases and understanding the
      association of PAR4 targeting for improved cardiac protection. Conclusively, this
      review highlights the importance of PAR4 antagonists and its potential utility in
      different CVDs.

PMID- 29443903
TI  - QLog Solar-Cell Mode Photodiode Logarithmic CMOS Pixel Using Charge Compression
      and Readout.
AB  - In this paper, we present a new logarithmic pixel design currently under
      development at New Imaging Technologies SA (NIT). This new logarithmic pixel
      design uses charge domain logarithmic signal compression and charge-transfer
      based signal readout. This structure gives a linear response in low light
      conditions and logarithmic response in high light conditions. The charge transfer
      readout efficiently suppresses the reset (KTC) noise by using true correlated
      double sampling (CDS) in low light conditions. In high light conditions, thanks
      to charge domain logarithmic compression, it has been demonstrated that 3000
      electrons should be enough to cover a 120 dB dynamic range with a mobile phone
      camera-like signal-to-noise ratio (SNR) over the whole dynamic range. This low
      electron count permits the use of ultra-small floating diffusion capacitance (sub
      fF) without charge overflow. The resulting large conversion gain permits a single
      photon detection capability with a wide dynamic range without a complex
      sensor/system design. A first prototype sensor with 320 * 240 pixels has been
      implemented to validate this charge domain logarithmic pixel concept and
      modeling. The first experimental results validate the logarithmic charge
      compression theory and the low readout noise due to the charge-transfer-based
      readout.

PMID- 29443902
TI  - Repurposing Plant Virus Nanoparticles.
AB  - Plants have been explored for many years as inexpensive and versatile platforms
      for the generation of vaccines and other biopharmaceuticals. Plant viruses have
      also been engineered to either express subunit vaccines or act as epitope
      presentation systems. Both icosahedral and helical, filamentous-shaped plant
      viruses have been used for these purposes. More recently, plant viruses have been
      utilized as nanoparticles to transport drugs and active molecules into cancer
      cells. The following review describes the use of both icosahedral and helical
      plant viruses in a variety of new functions against cancer. The review
      illustrates the breadth of variation among different plant virus nanoparticles
      and how this impacts the immune response.

PMID- 29443901
TI  - Toxicology of Engineered Nanoparticles: Focus on Poly(amidoamine) Dendrimers.
AB  - Engineered nanomaterials are increasingly being developed for paints, sunscreens,
      cosmetics, industrial lubricants, tyres, semiconductor devices, and also for
      biomedical applications such as in diagnostics, therapeutics, and contrast
      agents. As a result, nanomaterials are being manufactured, transported, and used
      in larger and larger quantities, and potential impacts on environmental and human
      health have been raised. Poly(amidoamine) (PAMAM) dendrimers are specifically
      suitable for biomedical applications. They are well-defined nanoscale molecules
      which contain a 2-carbon ethylenediamine core and primary amine groups at the
      surface. The systematically variable structural architecture and the large
      internal free volume make these dendrimers an attractive option for drug delivery
      and other biomedical applications. Due to the wide range of applications, the
      Organisation for Economic Co-Operation and Development (OECD) have included them
      in their list of nanoparticles which require toxicological assessment. Thus, the
      toxicological impact of these PAMAM dendrimers on human health and the
      environment is a matter of concern. In this review, the potential toxicological
      impact of PAMAM dendrimers on human health and environment is assessed,
      highlighting work to date exploring the toxicological effects of PAMAM
      dendrimers.

PMID- 29443904
TI  - Comparison of Conventional and Microwave Assisted Heating on Carbohydrate
      Content, Antioxidant Capacity and Postprandial Glycemic Response in Oat Meals.
AB  - Minimally processed cereal breakfast products from whole grain entered the market
      due to consumer demand of more nutritional food with more controlled sugar
      release. However, the subsequent processing of such products with different
      cooking methods in the consumer's kitchen may lead to significant differentiation
      of their nutritional value. Therefore, the evaluation of the impact of frequently
      used cooking methods on a final quality of breakfast cereals meal is needed. The
      present study investigates how the two different methods of heating, conventional
      and microwave (MW) assisted, affect the carbohydrate content, profile and
      resulting glycemic index of so prepared food as well as the antioxidant activity
      of meals. Two products available on the market-oat bran and flakes-were used. The
      highest starch content in fluid phase of oatmeal was detected in samples heated
      for 3 min with microwaves, regardless the type. The lowest starch content was
      obtained for 5 min MW heated flakes sample. The total content of glucose was
      about 1.5 times lower in bran vs. flakes oatmeal. The highest beta-glucan content
      in fluid fraction was also observed for bran meal but its release was independent
      of applied conditions.

PMID- 29443905
TI  - A Comparison of Military and Law Enforcement Body Armour.
AB  - Law-enforcement officers increasingly wear body armour for protection; wearing
      body armour is common practice in military populations. Law-enforcement and
      military occupational demands are vastly different and military-styled body
      armour may not be suitable for law-enforcement. This study investigated
      differences between selected military body armour (MBA: 6.4 kg) and law
      enforcement body armour (LEBA: 2.1 kg) in impacts on postural sway, vertical
      jump, agility, a functional movement screen (FMS), task simulations (vehicle
      exit; victim recovery), and subjective measures. Ten volunteer police officers
      (six females, four males) were randomly allocated to one of the designs on each
      of two days. Body armour type did not significantly affect postural sway,
      vertical jump, vehicle exit and 5 m sprint times, or victim recovery times. Both
      armour types increased sway velocity and sway-path length in the final five
      seconds compared to the first 5 s of a balance task. The MBA was associated with
      significantly slower times to complete the agility task, poorer FMS total scores,
      and poorer subjective ratings of performance and comfort. The LEBA was perceived
      as more comfortable and received more positive performance ratings during the
      agility test and task simulations. The impacts of MBA and LEBA differed
      significantly and they should not be considered interchangeable.

PMID- 29443906
TI  - A Single RF Emitter-Based Indoor Navigation Method for Autonomous Service Robots.
AB  - Location-aware services are one of the key elements of modern intelligent
      applications. Numerous real-world applications such as factory automation, indoor
      delivery, and even search and rescue scenarios require autonomous robots to have
      the ability to navigate in an unknown environment and reach mobile targets with
      minimal or no prior infrastructure deployment. This research investigates and
      proposes a novel approach of dynamic target localisation using a single RF
      emitter, which will be used as the basis of allowing autonomous robots to
      navigate towards and reach a target. Through the use of multiple directional
      antennae, Received Signal Strength (RSS) is compared to determine the most
      probable direction of the targeted emitter, which is combined with the distance
      estimates to improve the localisation performance. The accuracy of the position
      estimate is further improved using a particle filter to mitigate the fluctuating
      nature of real-time RSS data. Based on the direction information, a motion
      control algorithm is proposed, using Simultaneous Localisation and Mapping (SLAM)
      and A* path planning to enable navigation through unknown complex environments. A
      number of navigation scenarios were developed in the context of factory
      automation applications to demonstrate and evaluate the functionality and
      performance of the proposed system.

PMID- 29443907
TI  - Bioactive Films Containing Alginate-Pectin Composite Microbeads with Lactococcus
      lactis subsp. lactis: Physicochemical Characterization and Antilisterial
      Activity.
AB  - Novel bioactive films were developed from the incorporation of Lactococcus lactis
      into polysaccharide films. Two different biopolymers were tested: cellulose
      derivative (hydroxylpropylmethylcellulose (HPMC)) and corn starch. Lactic acid
      bacteria (LAB) free or previously encapsulated in alginate-pectin composite
      hydrogel microbeads were added directly to the film forming solution and films
      were obtained by casting. In order to study the impact of the incorporation of
      the protective culture into the biopolymer matrix, the water vapour permeability,
      oxygen permeability, optical and mechanical properties of the dry films were
      evaluated. Furthermore, the antimicrobial effect of bioactive films against
      Listeria monocytogenes was studied in synthetic medium. Results showed that the
      addition of LAB or alginate-pectin microbeads modified slightly films optical
      properties. In comparison with HPMC films, starch matrix proves to be more
      sensitive to the addition of bacterial cells or beads. Indeed, mechanical
      resistance of corn starch films was lower but barrier properties were improved,
      certainly related to the possible establishment of interactions between alginate
      pectin beads and starch. HPMC and starch films containing encapsulated bioactive
      culture showed a complete inhibition of listerial growth during the first five
      days of storage at 5  degrees C and a reduction of 5 logs after 12 days.

PMID- 29443910
TI  - The Preparation and Optical Properties of Novel LiLa(MoO4)2:Sm3+,Eu3+ Red
      Phosphor.
AB  - Novel LiLa1-x-y(MoO4)2:xSm3+,yEu3+ (in short: LL1-x-yM:xSm3+,yEu3+) double
      molybdate red phosphors were synthesized by a solid-state reaction at as low
      temperature as 610  degrees C. The optimal doping concentration of Sm3+ in LiLa1
      x(MoO4)2:xSm3+ (LL1-xM:xSm3+) phosphor is x = 0.05 and higher concentrations lead
      to emission quenching by the electric dipole-electric dipole mechanism. In the
      samples co-doped with Eu3+ ions, the absorption spectrum in the near ultraviolet
      and blue regions became broader and stronger than these of the Sm3+ single-doped
      samples. The efficient energy transfer from Sm3+ to Eu3+ was found and the energy
      transfer efficiency was calculated. Under the excitation at 403 nm, the
      chromaticity coordinates of LL0.95-yM:0.05Sm3+,yEu3+ approach to the NTSC
      standard values (0.670, 0.330) continuously with increasing Eu3+ doping
      concentration. The phosphor exhibits high luminous efficiency under near UV or
      blue light excitation and remarkable thermal stability. At 150  degrees C, the
      integrated emission intensity of the Eu3+ remained 85% of the initial intensity
      at room temperature and the activation energy is calculated to be 0.254 eV. The
      addition of the LL0.83M:0.05Sm3+,0.12Eu3+ red phosphors can improve the color
      purity and reduce the correlated color temperature of WLED lamps. Hence, LL1-x
      yM:xSm3+,yEu3+ is a promising WLED red phosphor.

PMID- 29443908
TI  - Mosquitoes as Suitable Vectors for Alphaviruses.
AB  - Alphaviruses are arthropod-borne viruses and are predominantly transmitted via
      mosquito vectors. This vector preference by alphaviruses raises the important
      question of the determinants that contribute to vector competence. There are
      several tissue barriers of the mosquito that the virus must overcome in order to
      establish a productive infection. Of importance are the midgut, basal lamina and
      the salivary glands. Infection of the salivary glands is crucial for virus
      transmission during the mosquito's subsequent bloodfeed. Other factors that may
      contribute to vector competence include the microflora and parasites present in
      the mosquito, environmental conditions, the molecular determinants of the virus
      to adapt to the vector, as well as the effect of co-infection with other viruses.
      Though mosquito innate immunity is a contributing factor to vector competence, it
      will not be discussed in this review. Detailed understanding of these factors
      will be instrumental in minimising transmission of alphaviral diseases.

PMID- 29443909
TI  - Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and In
      Vitro Testing.
AB  - Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent class III histone
      deacetylases, which have been linked to the pathogenesis of numerous diseases,
      including HIV, metabolic disorders, neurodegeneration and cancer. Docking of the
      virtual pan-African natural products library (p-ANAPL), followed by in vitro
      testing, resulted in the identification of two inhibitors of sirtuin 1, 2 and 3
      (sirt1-3). Two bichalcones, known as rhuschalcone IV (8) and an analogue of
      rhuschalcone I (9), previously isolated from the medicinal plant Rhus pyroides,
      were shown to be active in the in vitro assay. The rhuschalcone I analogue (9)
      showed the best activity against sirt1, with an IC50 value of 40.8 uM. Based on
      the docking experiments, suggestions for improving the biological activities of
      the newly identified hit compounds have been provided.

PMID- 29443911
TI  - Discovery of 2-(4-Substituted-piperidin/piperazine-1-yl)-N-(5-cyclopropyl-1H
      pyrazol-3-yl)-quinazoline-2,4-diamines as PAK4 Inhibitors with Potent A549 Cell
      Proliferation, Migration, and Invasion Inhibition Activity.
AB  - A series of novel 2,4-diaminoquinazoline derivatives were designed, synthesized,
      and evaluated as p21-activated kinase 4 (PAK4) inhibitors. All compounds showed
      significant inhibitory activity against PAK4 (half-maximal inhibitory
      concentration IC50 < 1 MUM). Among them, compounds 8d and 9c demonstrated the
      most potent inhibitory activity against PAK4 (IC50 = 0.060 MUM and 0.068 MUM,
      respectively). Furthermore, we observed that compounds 8d and 9c displayed potent
      antiproliferative activity against the A549 cell line and inhibited cell cycle
      distribution, migration, and invasion of this cell line. In addition, molecular
      docking analysis was performed to predict the possible binding mode of compound
      8d. This series of compounds has the potential for further development as PAK4
      inhibitors for anticancer activity.

PMID- 29443912
TI  - Influence of Scanning Strategies on Processing of Aluminum Alloy EN AW 2618 Using
      Selective Laser Melting.
AB  - This paper deals with various selective laser melting (SLM) processing strategies
      for aluminum 2618 powder in order to get material densities and properties close
      to conventionally-produced, high-strength 2618 alloy. To evaluate the influence
      of laser scanning strategies on the resulting porosity and mechanical properties
      a row of experiments was done. Three types of samples were used: single-track
      welds, bulk samples and samples for tensile testing. Single-track welds were used
      to find the appropriate processing parameters for achieving continuous and well
      shaped welds. The bulk samples were built with different scanning strategies with
      the aim of reaching a low relative porosity of the material. The combination of
      the chessboard strategy with a 2 * 2 mm field size fabricated with an out-in
      spiral order was found to eliminate a major lack of fusion defects. However,
      small cracks in the material structure were found over the complete range of
      tested parameters. The decisive criteria was the elimination of small cracks that
      drastically reduced mechanical properties. Reduction of the thermal gradient
      using support structures or fabrication under elevated temperatures shows a
      promising approach to eliminating the cracks. Mechanical properties of samples
      produced by SLM were compared with the properties of extruded material. The
      results showed that the SLM-processed 2618 alloy could only reach one half of the
      yield strength and tensile strength of extruded material. This is mainly due to
      the occurrence of small cracks in the structure of the built material.

PMID- 29443913
TI  - Development of Functional Phthalocyanine-Based Associate towards an Effective
      Fluorimetric Detection of Hg(II).
AB  - In acidic media, cationic phthalocyanine Alcian blue 8GX, has an efficient
      fluorescence quenching effect on anionic phthalocyanine tetrasulphoaluminium
      phthalocyanines (AlS4Pc), forming an almost non-fluorescent associate. Based on
      this discovery, a red-emitting fluorescent probe consisted of AlS4PC and Alcian
      blue 8GX has been developed through molecular assembly. Further studies indicated
      that the presence of Hg(II) ion has a significant fluorescence recovery effect of
      the probe. Notably, only Hg(II) can significantly restore the fluorescence of
      AlS4Pc-Alcian blue 8GX system which was revealed from the screening experiments
      of common metal ions, which confirmed that the fluorescence recovery by other
      metal ions is very weak or even unrestored, showing high specificity and
      sensitivity AlS4Pc-Alcian blue 8GX to Hg(II). Thus, a new fluorimetry for Hg(II)
      with high specificity and high sensitivity in a wide concentration range has been
      established using AlS4Pc-Alcian blue 8GX associate as a red-emitting fluorescent
      probe. It is more noteworthy that this study opens a new way for development and
      application of functional phthalocyanine based red-emitting fluorescent probes.

PMID- 29443914
TI  - Using Unmanned Aerial Vehicles in Postfire Vegetation Survey Campaigns through
      Large and Heterogeneous Areas: Opportunities and Challenges.
AB  - This study evaluated the opportunities and challenges of using drones to obtain
      multispectral orthomosaics at ultra-high resolution that could be useful for
      monitoring large and heterogeneous burned areas. We conducted a survey using an
      octocopter equipped with a Parrot SEQUOIA multispectral camera in a 3000 ha
      framework located within the perimeter of a megafire in Spain. We assessed the
      quality of both the camera raw imagery and the multispectral orthomosaic
      obtained, as well as the required processing capability. Additionally, we
      compared the spatial information provided by the drone orthomosaic at ultra-high
      spatial resolution with another image provided by the WorldView-2 satellite at
      high spatial resolution. The drone raw imagery presented some anomalies, such as
      horizontal banding noise and non-homogeneous radiometry. Camera locations showed
      a lack of synchrony of the single frequency GPS receiver. The georeferencing
      process based on ground control points achieved an error lower than 30 cm in X-Y
      and lower than 55 cm in Z. The drone orthomosaic provided more information in
      terms of spatial variability in heterogeneous burned areas in comparison with the
      WorldView-2 satellite imagery. The drone orthomosaic could constitute a viable
      alternative for the evaluation of post-fire vegetation regeneration in large and
      heterogeneous burned areas.

PMID- 29443915
TI  - Quantification of Stable Isotope Traces Close to Natural Enrichment in Human
      Plasma Metabolites Using Gas Chromatography-Mass Spectrometry.
AB  - Currently, changes in metabolic fluxes following consumption of stable isotope
      enriched foods are usually limited to the analysis of postprandial kinetics of
      glucose. Kinetic information on a larger diversity of metabolites is often
      lacking, mainly due to the marginal percentage of fully isotopically enriched
      plant material in the administered food product, and hence, an even weaker 13C
      enrichment in downstream plasma metabolites. Therefore, we developed an
      analytical workflow to determine weak 13C enrichments of diverse plasma
      metabolites with conventional gas chromatography-mass spectrometry (GC-MS). The
      limit of quantification was increased by optimizing (1) the metabolite extraction
      from plasma, (2) the GC-MS measurement, and (3) most importantly, the
      computational data processing. We applied our workflow to study the catabolic
      dynamics of 13C-enriched wheat bread in three human subjects. For that purpose,
      we collected time-resolved human plasma samples at 16 timepoints after the
      consumption of 13C-labeled bread and quantified 13C enrichment of 12 metabolites
      (glucose, lactate, alanine, glycine, serine, citrate, glutamate, glutamine,
      valine, isoleucine, tyrosine, and threonine). Based on isotopomer specific
      analysis, we were able to distinguish catabolic profiles of starch and protein
      hydrolysis. More generally, our study highlights that conventional GC-MS
      equipment is sufficient to detect isotope traces below 1% if an appropriate data
      processing is integrated.

PMID- 29443916
TI  - Mexican-Hat-Like Response in a Flexible Tactile Sensor Using a Magnetorheological
      Elastomer.
AB  - A significant challenge in robotics is providing a sense of touch to robots. Even
      though several types of flexible tactile sensors have been proposed, they still
      have various technical issues such as a large amount of deformation that
      fractures the sensing elements, a poor maintainability and a deterioration in the
      sensitivity caused by the presence of a thick and soft covering. As one solution
      for these issues, we proposed a flexible tactile sensor composed of a magnet,
      magnetic transducer and dual-layer elastomer, which consists of a
      magnetorheological and nonmagnetic elastomer sheet. In this study, we first
      investigated the sensitivity of the sensor, which was found to be high
      (approximately 161 mV/N with a signal-to-noise ratio of 42.2 dB); however, the
      sensor has a speed-dependent hysteresis in its sensor response curve. Then, we
      investigated the spatial response and observed the following results: (1) the
      sensor response was a distorted Mexican-hat-like bipolar shape, namely a negative
      response area was observed around the positive response area; (2) the negative
      response area disappeared when we used a compressible sponge sheet instead of the
      incompressible nonmagnetic elastomer. We concluded that the characteristic
      negative response in the Mexican-hat-like response is derived from the
      incompressibility of the nonmagnetic elastomer.

PMID- 29443917
TI  - Detection of Thrombin Based on Fluorescence Energy Transfer between
      Semiconducting Polymer Dots and BHQ-Labelled Aptamers.
AB  - Carboxyl-functionalized semiconducting polymer dots (Pdots) were synthesized as
      an energy donor by the nanoprecipitation method. A black hole quenching dye (BHQ
      labelled thrombin aptamers) was used as the energy acceptor, and fluorescence
      resonance energy transfer between the aptamers and Pdots was used for
      fluorescence quenching of the Pdots. The addition of thrombin restored the
      fluorescence intensity. Under the optimized experimental conditions, the
      fluorescence of the system was restored to the maximum when the concentration of
      thrombin reached 130 nM, with a linear range of 0-50 nM (R2 = 0.990) and a
      detection limit of 0.33 nM. This sensor was less disturbed by impurities, showing
      good specificity and signal response to thrombin, with good application in actual
      samples. The detection of human serum showed good linearity in the range of 0-30
      nM (R2 = 0.997), with a detection limit of 0.56 nM and a recovery rate of 96.2
      104.1%, indicating that this fluorescence sensor can be used for the detection of
      thrombin content in human serum.

PMID- 29443918
TI  - Error Modelling for Multi-Sensor Measurements in Infrastructure-Free Indoor
      Navigation.
AB  - The long-term objective of our research is to develop a method for infrastructure
      free simultaneous localization and mapping (SLAM) and context recognition for
      tactical situational awareness. Localization will be realized by propagating
      motion measurements obtained using a monocular camera, a foot-mounted Inertial
      Measurement Unit (IMU), sonar, and a barometer. Due to the size and weight
      requirements set by tactical applications, Micro-Electro-Mechanical (MEMS)
      sensors will be used. However, MEMS sensors suffer from biases and drift errors
      that may substantially decrease the position accuracy. Therefore, sophisticated
      error modelling and implementation of integration algorithms are key for
      providing a viable result. Algorithms used for multi-sensor fusion have
      traditionally been different versions of Kalman filters. However, Kalman filters
      are based on the assumptions that the state propagation and measurement models
      are linear with additive Gaussian noise. Neither of the assumptions is correct
      for tactical applications, especially for dismounted soldiers, or rescue
      personnel. Therefore, error modelling and implementation of advanced fusion
      algorithms are essential for providing a viable result. Our approach is to use
      particle filtering (PF), which is a sophisticated option for integrating
      measurements emerging from pedestrian motion having non-Gaussian error
      characteristics. This paper discusses the statistical modelling of the
      measurement errors from inertial sensors and vision based heading and translation
      measurements to include the correct error probability density functions (pdf) in
      the particle filter implementation. Then, model fitting is used to verify the
      pdfs of the measurement errors. Based on the deduced error models of the
      measurements, particle filtering method is developed to fuse all this
      information, where the weights of each particle are computed based on the
      specific models derived. The performance of the developed method is tested via
      two experiments, one at a university's premises and another in realistic tactical
      conditions. The results show significant improvement on the horizontal
      localization when the measurement errors are carefully modelled and their
      inclusion into the particle filtering implementation correctly realized.

PMID- 29443919
TI  - A Novel Strategy for Very-Large-Scale Cash-Crop Mapping in the Context of Weather
      Related Risk Assessment, Combining Global Satellite Multispectral Datasets,
      Environmental Constraints, and In Situ Acquisition of Geospatial Data.
AB  - Cash crops are agricultural crops intended to be sold for profit as opposed to
      subsistence crops, meant to support the producer, or to support livestock. Since
      cash crops are intended for future sale, they translate into large financial
      value when considered on a wide geographical scale, so their production directly
      involves financial risk. At a national level, extreme weather events including
      destructive rain or hail, as well as drought, can have a significant impact on
      the overall economic balance. It is thus important to map such crops in order to
      set up insurance and mitigation strategies. Using locally generated data-such as
      municipality-level records of crop seeding-for mapping purposes implies facing a
      series of issues like data availability, quality, homogeneity, etc. We thus opted
      for a different approach relying on global datasets. Global datasets ensure
      homogeneity and availability of data, although sometimes at the expense of
      precision and accuracy. A typical global approach makes use of spaceborne remote
      sensing, for which different land cover classification strategies are available
      in literature at different levels of cost and accuracy. We selected the optimal
      strategy in the perspective of a global processing chain. Thanks to a
      specifically developed strategy for fusing unsupervised classification results
      with environmental constraints and other geospatial inputs including ground-based
      data, we managed to obtain good classification results despite the constraints
      placed. The overall production process was composed using "good-enough"
      algorithms at each step, ensuring that the precision, accuracy, and data-hunger
      of each algorithm was commensurate to the precision, accuracy, and amount of data
      available. This paper describes the tailored strategy developed on the occasion
      as a cooperation among different groups with diverse backgrounds, a strategy
      which is believed to be profitably reusable in other, similar contexts. The paper
      presents the problem, the constraints and the adopted solutions; it then
      summarizes the main findings including that efforts and costs can be saved on the
      side of Earth Observation data processing when additional ground-based data are
      available to support the mapping task.

PMID- 29443920
TI  - Gradient-Type Magnetoelectric Current Sensor with Strong Multisource Noise
      Suppression.
AB  - A novel gradient-type magnetoelectric (ME) current sensor operating in magnetic
      field gradient (MFG) detection and conversion mode is developed based on a pair
      of ME composites that have a back-to-back capacitor configuration under a
      baseline separation and a magnetic biasing in an electrically-shielded and
      mechanically-enclosed housing. The physics behind the current sensing process is
      the product effect of the current-induced MFG effect associated with vortex
      magnetic fields of current-carrying cables (i.e., MFG detection) and the MFG
      induced ME effect in the ME composite pair (i.e., MFG conversion). The sensor
      output voltage is directly obtained from the gradient ME voltage of the ME
      composite pair and is calibrated against cable current to give the current
      sensitivity. The current sensing performance of the sensor is evaluated, both
      theoretically and experimentally, under multisource noises of electric fields,
      magnetic fields, vibrations, and thermals. The sensor combines the merits of
      small nonlinearity in the current-induced MFG effect with those of high
      sensitivity and high common-mode noise rejection rate in the MFG-induced ME
      effect to achieve a high current sensitivity of 0.65-12.55 mV/A in the frequency
      range of 10 Hz-170 kHz, a small input-output nonlinearity of <500 ppm, a small
      thermal drift of <0.2%/C in the current range of 0-20 A, and a high common-mode
      noise rejection rate of 17-28 dB from multisource noises.

PMID- 29443921
TI  - Calcium Chloride and Calcium Gluconate in Neonatal Parenteral Nutrition Solutions
      without Cysteine: Compatibility Studies Using Laser Light Obscuration
      Methodology.
AB  - There are no compatibility studies for neonatal parenteral nutrition solutions
      without cysteine containing calcium chloride or calcium gluconate using light
      obscuration as recommended by the United States Pharmacopeia (USP). The purpose
      of this study was to do compatibility testing for solutions containing calcium
      chloride and calcium gluconate without cysteine. Solutions of TrophAmine and
      Premasol (2.5% amino acids), containing calcium chloride or calcium gluconate
      were compounded without cysteine. Solutions were analyzed for particle counts
      using light obscuration. Maximum concentrations tested were 15 mmol/L of calcium
      and 12.5 mmol/L of phosphate. If the average particle count of three replicates
      exceeded USP guidelines, the solution was determined to be incompatible. This
      study found that 12.5 and 10 mmol/L of calcium and phosphate, respectively, are
      compatible in neonatal parenteral nutrition solutions compounded with 2.5% amino
      acids of either TrophAmine or Premasol. There did not appear to be significant
      differences in compatibility for solutions containing TrophAmine or Premasol when
      solutions were compounded with either CaCl2 or CaGlu-Pl. This study presents data
      in order to evaluate options for adding calcium and phosphate to neonatal
      parenteral nutrition solutions during shortages of calcium and cysteine.

PMID- 29443923
TI  - On the Comparison of Wearable Sensor Data Fusion to a Single Sensor Machine
      Learning Technique in Fall Detection.
AB  - In the context of the ageing global population, researchers and scientists have
      tried to find solutions to many challenges faced by older people. Falls, the
      leading cause of injury among elderly, are usually severe enough to require
      immediate medical attention; thus, their detection is of primary importance. To
      this effect, many fall detection systems that utilize wearable and ambient
      sensors have been proposed. In this study, we compare three newly proposed data
      fusion schemes that have been applied in human activity recognition and fall
      detection. Furthermore, these algorithms are compared to our recent work
      regarding fall detection in which only one type of sensor is used. The results
      show that fusion algorithms differ in their performance, whereas a machine
      learning strategy should be preferred. In conclusion, the methods presented and
      the comparison of their performance provide useful insights into the problem of
      fall detection.

PMID- 29443922
TI  - Effects of an Acute Exercise Bout on Serum Hepcidin Levels.
AB  - Iron deficiency is a frequent and multifactorial disorder in the career of
      athletes, particularly in females. Exercise-induced disturbances in iron
      homeostasis produce deleterious effects on performance and adaptation to
      training; thus, the identification of strategies that restore or maintain iron
      homeostasis in athletes is required. Hepcidin is a liver-derived hormone that
      degrades the ferroportin transport channel, thus reducing the ability of
      macrophages to recycle damaged iron, and decreasing iron availability. Although
      it has been suggested that the circulating fraction of hepcidin increases during
      early post-exercise recovery (~3 h), it remains unknown how an acute exercise
      bout may modify the circulating expression of hepcidin. Therefore, the current
      review aims to determine the post-exercise expression of serum hepcidin in
      response to a single session of exercise. The review was carried out in the
      Dialnet, Elsevier, Medline, Pubmed, Scielo and SPORTDiscus databases, using
      hepcidin (and "exercise" or "sport" or "physical activity") as a strategy of
      search. A total of 19 articles were included in the review after the application
      of the inclusion/exclusion criteria. This search found that a single session of
      endurance exercise (intervallic or continuous) at moderate or vigorous intensity
      (60-90% VO2peak) stimulates an increase in the circulating levels of hepcidin
      between 0 h and 6 h after the end of the exercise bout, peaking at ~3 h post
      exercise. The magnitude of the response of hepcidin to exercise seems to be
      dependent on the pre-exercise status of iron (ferritin) and inflammation (IL-6).
      Moreover, oxygen disturbances and the activation of a hypoxia-induced factor
      during or after exercise may stimulate a reduction of hepcidin expression.
      Meanwhile, cranberry flavonoids supplementation promotes an anti-oxidant effect
      that may facilitate the post-exercise expression of hepcidin. Further studies are
      required to explore the effect of resistance exercise on hepcidin expression.

PMID- 29443924
TI  - Identification of Key Pathways and Genes in the Dynamic Progression of HCC Based
      on WGCNA.
AB  - Hepatocellular carcinoma (HCC) is a devastating disease worldwide. Though many
      efforts have been made to elucidate the process of HCC, its molecular mechanisms
      of development remain elusive due to its complexity. To explore the stepwise
      carcinogenic process from pre-neoplastic lesions to the end stage of HCC, we
      employed weighted gene co-expression network analysis (WGCNA) which has been
      proved to be an effective method in many diseases to detect co-expressed modules
      and hub genes using eight pathological stages including normal, cirrhosis without
      HCC, cirrhosis, low-grade dysplastic, high-grade dysplastic, very early and
      early, advanced HCC and very advanced HCC. Among the eight consecutive
      pathological stages, five representative modules are selected to perform
      canonical pathway enrichment and upstream regulator analysis by using ingenuity
      pathway analysis (IPA) software. We found that cell cycle related biological
      processes were activated at four neoplastic stages, and the degree of activation
      of the cell cycle corresponded to the deterioration degree of HCC. The orange and
      yellow modules enriched in energy metabolism, especially oxidative metabolism,
      and the expression value of the genes decreased only at four neoplastic stages.
      The brown module, enriched in protein ubiquitination and ephrin receptor
      signaling pathways, correlated mainly with the very early stage of HCC. The
      darkred module, enriched in hepatic fibrosis/hepatic stellate cell activation,
      correlated with the cirrhotic stage only. The high degree hub genes were
      identified based on the protein-protein interaction (PPI) network and were
      verified by Kaplan-Meier survival analysis. The novel five high degree hub genes
      signature that was identified in our study may shed light on future prognostic
      and therapeutic approaches. Our study brings a new perspective to the
      understanding of the key pathways and genes in the dynamic changes of HCC
      progression. These findings shed light on further investigations.

PMID- 29443925
TI  - PClass: Protein Quaternary Structure Classification by Using Bootstrapping
      Strategy as Model Selection.
AB  - Protein quaternary structure complex is also known as a multimer, which plays an
      important role in a cell. The dimer structure of transcription factors is
      involved in gene regulation, but the trimer structure of virus-infection
      associated glycoproteins is related to the human immunodeficiency virus. The
      classification of the protein quaternary structure complex for the post-genome
      era of proteomics research will be of great help. Classification systems among
      protein quaternary structures have not been widely developed. Therefore, we
      designed the architecture of a two-layer machine learning technique in this
      study, and developed the classification system PClass. The protein quaternary
      structure of the complex is divided into five categories, namely, monomer, dimer,
      trimer, tetramer, and other subunit classes. In the framework of the bootstrap
      method with a support vector machine, we propose a new model selection method.
      Each type of complex is classified based on sequences, entropy, and accessible
      surface area, thereby generating a plurality of feature modules. Subsequently,
      the optimal model of effectiveness is selected as each kind of complex feature
      module. In this stage, the optimal performance can reach as high as 70% of
      Matthews correlation coefficient (MCC). The second layer of construction combines
      the first-layer module to integrate mechanisms and the use of six machine
      learning methods to improve the prediction performance. This system can be
      improved over 10% in MCC. Finally, we analyzed the performance of our
      classification system using transcription factors in dimer structure and virus
      infection-associated glycoprotein in trimer structure. PClass is available via a
      web interface at http://predictor.nchu.edu.tw/PClass/.

PMID- 29443926
TI  - The Pleiotropic Effects of the Canonical Wnt Pathway in Early Development and
      Pluripotency.
AB  - The technology to derive embryonic and induced pluripotent stem cells from early
      embryonic stages and adult somatic cells, respectively, emerged as a powerful
      resource to enable the establishment of new in vitro models, which recapitulate
      early developmental processes and disease. Additionally, pluripotent stem cells
      (PSCs) represent an invaluable source of relevant differentiated cell types with
      immense potential for regenerative medicine and cell replacement therapies.
      Pluripotent stem cells support self-renewal, potency and proliferation for
      extensive periods of culture in vitro. However, the core pathways that rule each
      of these cellular features specific to PSCs only recently began to be clarified.
      The Wnt signaling pathway is pivotal during early embryogenesis and is central
      for the induction and maintenance of the pluripotency of PSCs. Signaling by the
      Wnt family of ligands is conveyed intracellularly by the stabilization of beta
      catenin in the cytoplasm and in the nucleus, where it elicits the transcriptional
      activity of T-cell factor (TCF)/lymphoid enhancer factor (LEF) family of
      transcription factors. Interestingly, in PSCs, the Wnt/beta-catenin-TCF/LEF axis
      has several unrelated and sometimes opposite cellular functions such as self
      renewal, stemness, lineage commitment and cell cycle regulation. In addition,
      tight control of the Wnt signaling pathway enhances reprogramming of somatic
      cells to induced pluripotency. Several recent research efforts emphasize the
      pleiotropic functions of the Wnt signaling pathway in the pluripotent state.
      Nonetheless, conflicting results and unanswered questions still linger. In this
      review, we will focus on the diverse functions of the canonical Wnt signaling
      pathway on the developmental processes preceding embryo implantation, as well as
      on its roles in pluripotent stem cell biology such as self-renewal and cell cycle
      regulation and somatic cell reprogramming.

PMID- 29443927
TI  - AIEgen-Based Fluorescent Nanomaterials: Fabrication and Biological Applications.
AB  - In recent years, luminogens with the feature of aggregation-induced emission
      (AIEgen) have emerged as advanced luminescent materials for fluorescent
      nanomaterial preparation. AIEgen-based nanomaterials show enhanced fluorescence
      efficiency and superior photostability, which thusly offer unique advantages in
      biological applications. In this review, we will summarize the fabrication
      methods of AIEgen-based nanomaterials and their applications in in vitro/in vivo
      imaging, cell tracing, photodynamic therapy and drug delivery, focusing on the
      recent progress.

PMID- 29443928
TI  - Changes in the Anti-Allergic Activities of Sesame by Bioconversion.
AB  - Sesame is an important oilseed crop, which has been used as a traditional health
      food to ameliorate the prevention of various diseases. We evaluated the changes
      in the anti-allergic activities of sesame by bioconversion. SDS-PAGE of non
      fermented sesame proteins showed major allergen bands, while that of fermented
      sesame showed only a few protein bands. Additionally, we investigated the
      effectiveness of fermented sesame by bioconversion in tumor necrosis factor-alpha
      (TNF-alpha)- and interferon-gamma (IFN-gamma)-induced HaCaT cells. In HaCaT
      cells, fermented sesame inhibited the mRNA expression of interleukin-6 (IL-6) and
      interleukin-1beta (IL-1beta), thymus and macrophage-derived chemokine
      (MDC/CCL22), activation-regulated chemokine (TARC/CCL17), and intercellular
      adhesion molecule-1 (ICAM-1). Moreover, fermented sesame inhibited the activation
      of nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of
      transcription 1 (STAT1). Fermented sesame exerts anti-allergic effects by
      suppressing the expression of chemokines and cytokines via blockade of NF-kappaB
      and STAT1 activation.

PMID- 29443931
TI  - Robust Automatic Target Recognition via HRRP Sequence Based on Scatterer
      Matching.
AB  - High resolution range profile (HRRP) plays an important role in wideband radar
      automatic target recognition (ATR). In order to alleviate the sensitivity to
      clutter and target aspect, employing a sequence of HRRP is a promising approach
      to enhance the ATR performance. In this paper, a novel HRRP sequence-matching
      method based on singular value decomposition (SVD) is proposed. First, the HRRP
      sequence is decoupled into the angle space and the range space via SVD, which
      correspond to the span of the left and the right singular vectors, respectively.
      Second, atomic norm minimization (ANM) is utilized to estimate dominant
      scatterers in the range space and the Hausdorff distance is employed to measure
      the scatter similarity between the test and training data. Next, the angle space
      similarity between the test and training data is evaluated based on the left
      singular vector correlations. Finally, the range space matching result and the
      angle space correlation are fused with the singular values as weights. Simulation
      and outfield experimental results demonstrate that the proposed matching metric
      is a robust similarity measure for HRRP sequence recognition.

PMID- 29443929
TI  - Claimed Effects, Outcome Variables and Methods of Measurement for Health Claims
      on Foods Related to Vision Proposed Under Regulation (EC) 1924/2006.
AB  - Adequate visual function has a strong impact on the quality of life of people.
      Several foods and food components have been hypothesized to play a role in the
      maintenance of normal visual function and in the prevention of eye diseases. Some
      of these foods/food components have been the object of a request of authorization
      for use of health claims under Articles 13(5) or 14 of the Regulation (EC)
      1924/2006. Most of these requests have received a negative opinion from the
      European Food Safety Authority (EFSA) due to the choice of inappropriate outcome
      variables (OVs) and/or methods of measurement (MMs) applied in the studies used
      to substantiate the claims. This manuscript refers to the collection, collation
      and critical analysis of OVs and MMs related to vision. Guidance document and
      requests for authorization of health claims were used to collect OVs and MMs
      related to vision. A literature review was performed to critically analyse OVs
      and MMs, with the aim of defining their appropriateness in the context of a
      specific claimed effect related to vision. The results highlight the importance
      of adequate choices of OVs and MMs for an effective substantiation of claims
      related to visual function.

PMID- 29443930
TI  - Imbalanced Nutrient Intake in Cancer Survivors from the Examination from the
      Nationwide Health Examination Center-Based Cohort.
AB  - This study was conducted to examine the nutrient intake status of cancer
      survivors. A total of 5224 cancer survivors, 19,926 non-cancer individuals
      without comorbidities (non-cancer I), and 20,622 non-cancer individuals with
      comorbidities, matched by age, gender, and recruitment center location were
      included in the analysis. Generally, the proportion of total energy from
      carbohydrates was higher and the proportion from fat was lower in cancer
      survivors. The odds ratios (ORs) for total energy (OR = 0.92, 95% confidence
      interval (CI) = 0.86-0.99), proportion of total energy from fat (OR = 0.54, 95%
      CI = 0.35-0.83), and protein (OR = 0.85, 95% CI = 0.79-0.90) were significantly
      lower, and the OR for the proportion of total energy from carbohydrates was
      higher (OR = 1.21, 95% CI = 1.10-1.33) in the cancer survivors than in non-cancer
      I. Additionally, the cancer survivors' protein, vitamin B1, vitamin B2, niacin,
      and phosphorus intakes were lower, whereas their vitamin C intake was higher.
      When divided by cancer type, the ORs for the carbohydrate percentages were
      significantly higher in the colon and breast cancer survivors, whereas protein
      intake was lower in gastric, breast, and cervical cancer survivors. The nutrient
      intake patterns in Asian cancer survivors are poor, with higher carbohydrate and
      lower fat and protein intakes.

PMID- 29443932
TI  - Relationships between Characteristics of Urban Green Land Cover and Mental Health
      in U.S. Metropolitan Areas.
AB  - Urbanization increases risk for depression and other mental disorders. A growing
      body of research indicates the natural environment confers numerous psychological
      benefits including alleviation of mental distress. This study examined land cover
      types and landscape metrics in relation to mental health for 276 U.S. counties
      within metropolitan areas having a population of 1 million or more. County Health
      Rankings and Behavioral Risk and Factor Surveillance System (BRFSS) provided a
      measure of mental health. The 2011 National Land Cover Database (NLCD) provided
      data on green land cover types, from which seven landscape metrics were generated
      to characterize landscape patterns. Spearman's rho correlation and stepwise
      logistic regression models, respectively, were employed to examine bivariate and
      multivariate relationships. Models were adjusted for county population and
      housing density, region, race, and income to account for potential confounding.
      Overall, individual measures of landscape patterns showed stronger associations
      with mental health than percent total cover alone. Greater edge contrast was
      associated with 3.81% lower odds of Frequent Mental Distress (FMD) (Adjusted
      Odd's Ratio (AOR) = 0.9619, 95% CI = 0.9371, 0.9860). Shrubland cohesion was
      associated with greater odds of FMD (AOR = 1.0751, 95% CI = 1.0196, 1.1379). In
      addition, distance between shrubland cover was associated with greater odds of
      FMD (AOR = 1.0027, 95% CI = 1.0016, 1.0041). Although effect sizes were small,
      findings suggest different types of landscape characteristics may have different
      roles in improving mental health.

PMID- 29443933
TI  - Mental Health Interventions for Parent Carers of Children with Autistic Spectrum
      Disorder: Practice Guidelines from a Critical Interpretive Synthesis (CIS)
      Systematic Review.
AB  - Parent carers of children with Autism Spectrum Disorder (ASD) often report
      increased levels of stress, depression, and anxiety. Unmet parent carer mental
      health needs pose a significant risk to the psychological, physical, and social
      well-being of the parents of the child affected by ASD and jeopardize the
      adaptive functioning of the family as well as the potential of the child affected
      by ASD. This systematic review identifies key qualities of interventions
      supporting the mental health of parent carers and proposes practitioner-parent
      carer support guidelines. A search of four databases (Medline, PubMed, PsycINFO,
      and Social Science Data) was conducted to identify studies that met the following
      criteria: (1) an intervention was delivered to parent carers of a child with ASD
      under the age of 18 years; (2) the research design allowed for a comparison on
      outcomes across groups; and (3) outcome measures of the parent carers' mental
      health were used. A total of 23 studies met the inclusion criteria. A critical
      interpretive synthesis approach was used to produce an integrated
      conceptualization of the evidence. Findings suggest practitioner guidelines to
      support the mental health and wellbeing of parent carers should include
      addressing the parent's self-perspective taking and skill for real time problem
      solving.

PMID- 29443934
TI  - Half-Sandwich Ru(II) and Os(II) Bathophenanthroline Complexes Containing a
      Releasable Dichloroacetato Ligand.
AB  - We report on the preparation and thorough characterization of cytotoxic half
      sandwich complexes [Ru(eta6-pcym)(bphen)(dca)]PF6 (Ru-dca) and [Os(eta6
      pcym)(bphen)(dca)]PF6 (Os-dca) containing dichloroacetate(1-) (dca) as the
      releasable O-donor ligand bearing its own cytotoxicity; pcym = 1-methyl-4-(propan
      2-yl)benzene (p-cymene), bphen = 4,7-diphenyl-1,10-phenanthroline
      (bathophenanthroline). Complexes Ru-dca and Os-dca hydrolyzed in the water
      containing media, which led to the dca ligand release (supported by 1H NMR and
      electrospray ionization mass spectra). Mass spectrometry studies revealed that
      complexes Ru-dca and Os-dca do not interact covalently with the model proteins
      cytochrome c and lysozyme. Both complexes exhibited slightly higher in vitro
      cytotoxicity (IC50 = 3.5 MUM for Ru-dca, and 2.6 MUM for Os-dca) against the
      A2780 human ovarian carcinoma cells than cisplatin (IC50 = 5.9 MUM), while their
      toxicity on the healthy human hepatocytes was found to be IC50 = 19.1 MUM for Ru
      dca and IC50 = 19.7 MUM for Os-dca. Despite comparable cytotoxicity of complexes
      Ru-dca and Os-dca, both the complexes modified the cell cycle, mitochondrial
      membrane potential, and mitochondrial cytochrome c release by a different way, as
      revealed by flow cytometry experiments. The obtained results point out the
      different mechanisms of action between the complexes.

PMID- 29443935
TI  - Modulation of Donor-Acceptor Distance in a Series of Carbazole Push-Pull Dyes; A
      Spectroscopic and Computational Study.
AB  - A series of eight carbazole-cyanoacrylate based donor-acceptor dyes were studied.
      Within the series the influence of modifying the thiophene bridge, linking donor
      and acceptor and a change in the nature of the acceptor, from acid to ester, was
      explored. In this joint experimental and computational study we have used
      electronic absorbance and emission spectroscopies, Raman spectroscopy and
      computational modeling (density functional theory). From these studies it was
      found that extending the bridge length allowed the lowest energy transition to be
      systematically red shifted by 0.12 eV, allowing for limited tuning of the
      absorption of dyes using this structural motif. Using the aforementioned
      techniques we demonstrate that this transition is charge transfer in nature.
      Furthermore, the extent of charge transfer between donor and acceptor decreases
      with increasing bridge length and the bridge plays a smaller role in
      electronically mixing with the acceptor as it is extended.

PMID- 29443937
TI  - PCR Diagnosis of Small Hive Beetles.
AB  - Small hive beetles (SHBs), Aethinatumida, are parasites of social bee colonies
      native to sub-Saharan Africa and have become an invasive species at a global
      scale. Reliable Polymerase Chain Reaction (PCR) diagnosis of this mandatory pest
      is required to limit its further spread and impact. Here, we have developed SHB
      primers, which amplify for 10 native African locations and 10 reported
      introductions, but not for three closely related species (Aethinaconcolor,
      Aethinaflavicollis, and Aethinainconspicua). We also show that adult honey bee
      workers can be used as matrices for PCR-based detection of SHBs. The sensitivity
      of this novel method appears to be 100%, which is identical to conventional
      visual screenings. Furthermore, the specificity of this novel approach was also
      high (90.91%). Since both sensitivity and specificity are high, we recommend this
      novel PCR method and the new primers for routine surveillance of hives in high
      risk areas.

PMID- 29443936
TI  - Ageing with HIV.
AB  - The population of people living with HIV (PLWH) is growing older with an
      estimated 4 million over the age of 50 years, a figure which has doubled since
      the introduction of effective antiretroviral therapy (ART) and which is
      increasing globally. Despite effective ART, PLWH still experience excess
      morbidity and mortality compared to the general population with increased
      prevalence of age-related, non-AIDS illnesses (NAI) such as cardiovascular
      disease, malignancies, cognitive impairment and reduced bone mineral density,
      which impact disability and everyday functioning. This review will discuss the
      challenges presented by comorbidities in ageing PLWH and discuss the aetiology
      and management of age-related illnesses in this vulnerable population.

PMID- 29443939
TI  - Occurrence of beta-N-methylamino-l-alanine (BMAA) and Isomers in Aquatic
      Environments and Aquatic Food Sources for Humans.
AB  - The neurotoxin beta-N-methylamino-l-alanine (BMAA), a non-protein amino acid
      produced by terrestrial and aquatic cyanobacteria and by micro-algae, has been
      suggested to play a role as an environmental factor in the neurodegenerative
      disease Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia complex (ALS-PDC).
      The ubiquitous presence of BMAA in aquatic environments and organisms along the
      food chain potentially makes it public health concerns. However, the BMAA
      associated human health risk remains difficult to rigorously assess due to
      analytical challenges associated with the detection and quantification of BMAA
      and its natural isomers, 2,4-diamino butyric acid (DAB), beta-amino-N-methyl
      alanine (BAMA) and N-(2-aminoethyl) glycine (AEG). This systematic review,
      reporting the current knowledge on the presence of BMAA and isomers in aquatic
      environments and human food sources, was based on a selection and a score
      numbering of the scientific literature according to various qualitative and
      quantitative criteria concerning the chemical analytical methods used. Results
      from the best-graded studies show that marine bivalves are to date the matrix
      containing the higher amount of BMAA, far more than most fish muscles, but with
      an exception for shark cartilage. This review discusses the available data in
      terms of their use for human health risk assessment and identifies knowledge gaps
      requiring further investigations.

PMID- 29443938
TI  - The Microbial Zoo in the C. elegans Intestine: Bacteria, Fungi and Viruses.
AB  - C. elegans is an invaluable model organism that has been a driving force in many
      fundamental biological discoveries. However, it is only in the past two decades
      that it has been applied to host-pathogen interaction studies. These studies have
      been facilitated by the discoveries of natural microbes that infect C. elegans,
      including bacteria, fungi and viruses. Notably, many of these microbes share a
      common site of infection, the C. elegans intestine. Furthermore, the recent
      descriptions of a natural gut microbiota in C. elegans raise the possibility that
      this could be a novel model system for microbiome and trans-kingdom interaction
      studies. Here we review studies of C. elegans host-microbe interactions with a
      particular focus on the intestine.

PMID- 29443940
TI  - Proteomic Differences in Feline Fibrosarcomas Grown Using Doxorubicin-Sensitive
      and -Resistant Cell Lines in the Chick Embryo Model.
AB  - Proteomic analyses are rapid and powerful tools that are used to increase the
      understanding of cancer pathogenesis, discover cancer biomarkers and predictive
      markers, and select and monitor novel targets for cancer therapy. Feline
      injection-site sarcomas (FISS) are aggressive skin tumours with high recurrence
      rates, despite treatment with surgery, radiotherapy, and chemotherapy.
      Doxorubicin is a drug of choice for soft tissue sarcomas, including FISS.
      However, multidrug resistance is one of the major causes of chemotherapy failure.
      The main aim of the present study was to identify proteins that differentiate
      doxorubicin-resistant from doxorubicin-sensitive FISS using two-dimensional gel
      electrophoresis (2DE), followed by matrix-assisted laser desorption ionisation
      time-of-flight mass spectrometry (MALDI-TOF MS) analysis. Using the three
      dimensional (3D) preclinical in ovo model, which resembles features of
      spontaneous fibrosarcomas, three significantly (p <= 0.05) differentially
      expressed proteins were identified in tumours grown from doxorubicin-resistant
      fibrosarcoma cell lines (FFS1 and FFS3) in comparison to the doxorubicin
      sensitive one (FFS5): Annexin A5 (ANXA5), Annexin A3 (ANXA3), and meiosis
      specific nuclear structural protein 1 (MNS1). Moreover, nine other proteins were
      significantly differentially expressed in tumours grown from the high doxorubicin
      resistant cell line (FFS1) in comparison to sensitive one (FFS5). This study may
      be the first proteomic fingerprinting of FISS reported, identifying potential
      candidates for specific predictive biomarkers and research targets for
      doxorubicin-resistant FISS.

PMID- 29443941
TI  - Cytokeratin-8 in Anaplastic Thyroid Carcinoma: More Than a Simple Structural
      Cytoskeletal Protein.
AB  - Anaplastic thyroid carcinoma (ATC) is almost universally fatal. Elevated keratin
      8 (KRT8) protein expression is an established diagnostic cancer biomarker in
      several epithelial cancers (but not ATC). Several keratins, including KRT8, have
      been suggested to have a role in cell biology beyond that of structural
      cytoskeletal proteins. Here, we provide evidence that KRT8 plays a direct role in
      the growth of ATCs. Genomic and transcriptomic analysis of >5000 patients
      demonstrates that KRT8 mutation and copy number amplification are frequently
      evident in epithelial-derived cancers. Carcinomas arising from diverse tissues
      exhibit KRT8 mRNA and protein overexpression when compared to normal tissue
      levels. Similarly, in a panel of patient-derived ATC cell lines and patient
      tumors, KRT8 expression shows a similar pattern. sh-RNA-mediated KRT8 knockdown
      in these cell lines increases apoptosis, whereas forced overexpression of KRT8
      confers resistance to apoptosis under peroxide-induced cell stress conditions. We
      further show that KRT8 protein binds to annexin A2, a protein known to mediate
      apoptosis as well as the redox pathway.

PMID- 29443942
TI  - Understanding the Effect of Particle Size and Processing on Almond Lipid
      Bioaccessibility through Microstructural Analysis: From Mastication to Faecal
      Collection.
AB  - We have previously reported on the low lipid bioaccessibility from almond seeds
      during digestion in the upper gastrointestinal tract (GIT). In the present study,
      we quantified the lipid released during artificial mastication from four almond
      meals: natural raw almonds (NA), roasted almonds (RA), roasted diced almonds (DA)
      and almond butter from roasted almonds (AB). Lipid release after mastication
      (8.9% from NA, 11.8% from RA, 12.4% from DA and 6.2% from AB) was used to
      validate our theoretical mathematical model of lipid bioaccessibility. The total
      lipid potentially available for digestion in AB was 94.0%, which included the
      freely available lipid resulting from the initial sample processing and the
      further small amount of lipid released from the intact almond particles during
      mastication. Particle size distributions measured after mastication in NA, RA and
      DA showed most of the particles had a size of 1000 um and above, whereas AB bolus
      mainly contained small particles (<850 um). Microstructural analysis of faecal
      samples from volunteers consuming NA, RA, DA and AB confirmed that some lipid in
      NA, RA and DA remained encapsulated within the plant tissue throughout digestion,
      whereas almost complete digestion was observed in the AB sample. We conclude that
      the structure and particle size of the almond meals are the main factors in
      regulating lipid bioaccessibility in the gut.

PMID- 29443943
TI  - A Comparative Study on Asymmetric Reduction of Ketones Using the Growing and
      Resting Cells of Marine-Derived Fungi.
AB  - Whole-cell biocatalysts offer a highly enantioselective, minimally polluting
      route to optically active alcohols. Currently, most of the whole-cell catalytic
      performance involves resting cells rather than growing cell biotransformation,
      which is one-step process that benefits from the simultaneous growth and
      biotransformation, eliminating the need for catalysts preparation. In this paper,
      asymmetric reduction of 14 aromatic ketones to the corresponding enantiomerically
      pure alcohols was successfully conducted using the growing and resting cells of
      marine-derived fungi under optimized conditions. Good yields and excellent
      enantioselectivities were achieved with both methods. Although substrate
      inhibition might be a limiting factor for growing cell biotransformation, the
      selected strain can still completely convert 10-mM substrates into the desired
      products. The resting cell biotransformation showed a capacity to be recycled
      nine times without a significant decrease in the activity. This is the first
      study to perform asymmetric reduction of ketones by one-step growing cell
      biotransformation.

PMID- 29443944
TI  - Differential Expression of Six Rnase2 and Three Rnase3 Paralogs Identified in
      Blunt Snout Bream in Response to Aeromonas hydrophila Infection.
AB  - Ribonucleases (Rnases)2 and Rnase3 belong to the ribonuclease A (RnaseA)
      superfamily. Apart from their role in molecular evolutionary and functional
      biological studies, these genes have also been studied in the context of defense
      against pathogen infection in mammals. However, expression patterns, structures
      and response to bacterial infection of the two genes in blunt snout bream
      (Megalobrama amblycephala) remain unknown. In this study, we identified multiple
      copies of Rnase2 (six) and Rnase3 (three) in the M. amblycephala genome. The nine
      genes all possess characteristics typical of the RnaseA superfamily. No
      expression was detected in the early developmental stages, while a weak
      expression was observed at 120 and 140 h post-fertilization (hpf) for Rnase2b,
      Rnase2c, Rnase2e and Rnase3a, suggesting that only three copies of Rnase2 and one
      of Rnase3 are expressed. Interestingly, only Rnase2e was up-regulated in the
      kidney of M. amblycephala after Aeromonas hydrophila infection, while Rnase3a was
      significantly up-regulated in liver, gut and blood after the infection. We
      conclude that the paralogs of Rnase3 are more susceptible to A. hydrophila
      infection than Rnase2. These results indicate that different Rnase2 and Rnase3
      paralogs suggest a role in the innate immune response of M. amblycephala to
      bacterial infection.

PMID- 29443945
TI  - Charged N-terminus of Influenza Fusion Peptide Facilitates Membrane Fusion.
AB  - Cleavage of hemagglutinin precursor (HA0) by cellular proteases results in the
      formation of two subunits, HA1 and HA2. The N-terminal fragment of HA2, named a
      fusion peptide (HAfp), possess a charged, amine N-terminus. It has been shown
      that the N-terminus of HAfp stabilizes the structure of a helical hairpin
      observed for a 23-amino acid long peptide (HAfp1-23), whose larger activity than
      HAfp1-20 has been demonstrated recently. In this paper, we analyze the effect of
      N-terminal charge on peptide-mediated fusion efficiency and conformation changes
      at the membrane interface by comparison with the corresponding N-acetylated
      peptides of 20- and 23-amino acid lengths. We found that higher fusogenic
      activities of peptides with unmodified amino termini correlates with their
      ability to form helical hairpin structures oriented perpendicularly to the
      membrane plane. Molecular dynamics simulations showed that acetylated peptides
      adopt open and surface-bound conformation more often, which induced less disorder
      of the phospholipid chains, as compared to species with unmodified amino termini.

PMID- 29443946
TI  - A Comparative Study of Human Saposins.
AB  - Saposins are small proteins implicated in trafficking and loading of lipids onto
      Cluster of Differentiation 1 (CD1) receptor proteins that in turn present lipid
      antigens to T cells and a variety of T-cell receptors, thus playing a crucial
      role in innate and adaptive immune responses in humans. Despite their low
      sequence identity, the four types of human saposins share a similar folding
      pattern consisting of four helices linked by three conserved disulfide bridges.
      However, their lipid-binding abilities as well as their activities in extracting,
      transporting and loading onto CD1 molecules a variety of sphingo- and
      phospholipids in biological membranes display two striking characteristics: a
      strong pH-dependence and a structural change between a compact, closed
      conformation and an open conformation. In this work, we present a comparative
      computational study of structural, electrostatic, and dynamic features of human
      saposins based upon their available experimental structures. By means of
      structural alignments, surface analyses, calculation of pH-dependent protonation
      states, Poisson-Boltzmann electrostatic potentials, and molecular dynamics
      simulations at three pH values representative of biological media where saposins
      fulfill their function, our results shed light into their intrinsic features. The
      similarities and differences in this class of proteins depend on tiny variations
      of local structural details that allow saposins to be key players in triggering
      responses in the human immune system.

PMID- 29443948
TI  - Shared Housing Arrangements in Germany-An Equitable Alternative to Long Term Care
      Services beyond Homes and Institutions?
AB  - Given the saliency of socio-demographic pressures, the highly restrictive
      definition of "need for care" characterizing the German long-term care system at
      its foundations in 1994 has since been subject to various expansionary reforms.
      This has translated into greater interest in innovative care models that provide
      more choice and flexibility to beneficiaries. One such model is 'shared housing
      arrangements' ("ambulant betreute Wohngemeinschaften"), where a small group of
      people rent private rooms, while sharing a common space, domestic support, and
      nursing care. Using interview and secondary data, this study examines the
      potential for such arrangements to provide an equitable alternative to care that
      is accessible to a larger population of beneficiaries than presently seen in
      Germany.

PMID- 29443947
TI  - Vertebrate Genome Evolution in the Light of Fish Cytogenomics and rDNAomics.
AB  - To understand the cytogenomic evolution of vertebrates, we must first unravel the
      complex genomes of fishes, which were the first vertebrates to evolve and were
      ancestors to all other vertebrates. We must not forget the immense time span
      during which the fish genomes had to evolve. Fish cytogenomics is endowed with
      unique features which offer irreplaceable insights into the evolution of the
      vertebrate genome. Due to the general DNA base compositional homogeneity of fish
      genomes, fish cytogenomics is largely based on mapping DNA repeats that still
      represent serious obstacles in genome sequencing and assembling, even in model
      species. Localization of repeats on chromosomes of hundreds of fish species and
      populations originating from diversified environments have revealed the
      biological importance of this genomic fraction. Ribosomal genes (rDNA) belong to
      the most informative repeats and in fish, they are subject to a more relaxed
      regulation than in higher vertebrates. This can result in formation of a literal
      'rDNAome' consisting of more than 20,000 copies with their high proportion
      employed in extra-coding functions. Because rDNA has high rates of transcription
      and recombination, it contributes to genome diversification and can form
      reproductive barrier. Our overall knowledge of fish cytogenomics grows rapidly by
      a continuously increasing number of fish genomes sequenced and by use of novel
      sequencing methods improving genome assembly. The recently revealed exceptional
      compositional heterogeneity in an ancient fish lineage (gars) sheds new light on
      the compositional genome evolution in vertebrates generally. We highlight the
      power of synergy of cytogenetics and genomics in fish cytogenomics, its potential
      to understand the complexity of genome evolution in vertebrates, which is also
      linked to clinical applications and the chromosomal backgrounds of speciation. We
      also summarize the current knowledge on fish cytogenomics and outline its main
      future avenues.

PMID- 29443949
TI  - Detection-Response Task-Uses and Limitations.
AB  - The Detection-Response Task is a method for assessing the attentional effects of
      cognitive load in a driving environment. Drivers are presented with a sensory
      stimulus every 3-5 s, and are asked to respond to it by pressing a button
      attached to their finger. Response times and hit rates are interpreted as
      indicators of the attentional effect of cognitive load. The stimuli can be
      visual, tactile and auditory, and are chosen based on the type of in-vehicle
      system or device that is being evaluated. Its biggest disadvantage is that the
      method itself also affects the driver's performance and secondary task completion
      times. Nevertheless, this is an easy to use and implement method, which allows
      relevant assessment and evaluation of in-vehicle systems. By following the
      recommendations and taking into account its limitations, researchers can obtain
      reliable and valuable results on the attentional effects of cognitive load on
      drivers.

PMID- 29443950
TI  - A Survey of Home Enteral Nutrition Practices and Reimbursement in the Asia
      Pacific Region.
AB  - Literature regarding the use of home enteral nutrition (HEN) and how it is
      reimbursed in the Asia Pacific region is limited. This research survey aims to
      determine the availability of HEN, the type of feeds and enteral access used,
      national reimbursement policies, the presence of nutrition support teams (NSTs),
      and clinical nutrition education in this region. An electronic questionnaire was
      sent to 20 clinical nutrition societies and leaders in the Asia Pacific region in
      August 2017, where thirteen countries responded. Comparison of HEN reimbursement
      and practice between countries of different income groups based on the World
      Bank's data was investigated. Financial support for HEN is only available in 40%
      of the countries. An association was found between availability of financial
      support for HEN and health expenditure (r = 0.63, p = 0.021). High and middle
      upper income countries use mainly commercial supplements for HEN, while lower
      middle income countries use mainly blenderized diet. The presence of NSTs is
      limited, and only present mainly in acute settings. Sixty percent of the
      countries indicated an urgent need for funding and reimbursement of HEN. This
      survey demonstrates the varied clinical and economic situation in the Asia
      Pacific region. There is a lack of reimbursement, clinical support, and
      inadequate educational opportunities, especially for the lower-middle income
      countries.

PMID- 29443952
TI  - Microhydration and the Enhanced Acidity of Free Radicals.
AB  - Recent theoretical research employing a continuum solvent model predicted that
      radical centers would enhance the acidity (RED-shift) of certain proton-donor
      molecules. Microhydration studies employing a DFT method are reported here with
      the aim of establishing the effect of the solvent micro-structure on the acidity
      of radicals with and without RED-shifts. Microhydration cluster structures were
      obtained for carboxyl, carboxy-ethynyl, carboxy-methyl, and hydroperoxyl
      radicals. The numbers of water molecules needed to induce spontaneous ionization
      were determined. The hydration clusters formed primarily round the CO2 units of
      the carboxylate-containing radicals. Only 4 or 5 water molecules were needed to
      induce ionization of carboxyl and carboxy-ethynyl radicals, thus corroborating
      their large RED-shifts.

PMID- 29443951
TI  - Oviposition Deterrent and Larvicidal and Pupaecidal Activity of Seven Essential
      Oils and their Major Components against Culex quinquefasciatus Say (Diptera:
      Culicidae): Synergism-antagonism Effects.
AB  - The larvicidal activity of essential oils cinnamon (Cinnamomumverum J. Presl),
      Mexican lime (Citrusaurantifolia Swingle) cumin (Cuminumcyminum Linnaeus), clove
      (Syzygiumaromaticum (L.) Merr. & L.M.Perry), laurel (Laurusnobilis Linnaeus),
      Mexican oregano (Lippiaberlandieri Schauer) and anise (Pimpinellaanisum
      Linnaeus)) and their major components are tested against larvae and pupae of
      Culexquinquefasciatus Say. Third instar larvae and pupae are used for
      determination of lethality and mortality. Essential oils with more than 90%
      mortality after a 30-min treatment are evaluated at different time intervals. Of
      the essential oils tested, anise and Mexican oregano are effective against
      larvae, with a median lethal concentration (LC50) of 4.7 and 6.5 ug/mL,
      respectively. Anise essential oil and t-anethole are effective against pupae,
      with LC50 values of 102 and 48.7 ug/mL, respectively. Oregano essential oil and
      carvacrol also have relevant activities. A kinetic analysis of the larvicidal
      activity, the oviposition deterrent effect and assays of the effects of the
      binary mixtures of chemical components are undertaken. Results show that anethole
      has synergistic effects with other constituents. This same effect is observed for
      carvacrol and thymol. Limonene shows antagonistic effect with beta-pinene. The
      high larvicidal and pupaecidal activities of essential oils and its components
      demonstrate that they can be potential substitutes for chemical compounds used in
      mosquitoes control programs.

PMID- 29443953
TI  - A Comparison of Cats (Felis silvestris catus) Housed in Groups and Single Cages
      at a Shelter: A Retrospective Matched Cohort Study.
AB  - The merits of various housing options for domestic cats in shelters have been
      debated. However, comparisons are difficult to interpret because cats are
      typically not able to be randomly assigned to different housing conditions. In
      the current study, we attempted to address some of these issues by creating a
      retrospective matched cohort of cats in two housing types. Cats in group housing
      (GH) were matched with cats in single housing (SH) that were the same age, sex,
      breed, coat color, and size. Altogether we were able to find a match for 110 GH
      cats. We compared these two groups on several measures related to their
      experience at the shelter such as moves and the development of behavioral
      problems. We also compared these groups on outcomes including length of stay,
      live release, and returns after adoption. We found that while the frequency of
      moves was similar in both groups, SH cats were more likely to be moved to offsite
      facilities than GH cats. SH cats also spent a smaller proportion of time on the
      adoption floor. Length of stay and, live release and returns after adoption did
      not significantly differ across groups, however GH cats were two times as likely
      to be returned after adoption. Future research should look at the behavioral
      impacts of shelter decision-making regarding moving and management of cats in
      different housing systems.

PMID- 29443954
TI  - Adsorption Behavior of Selective Recognition Functionalized Biochar to Cd(II) in
      Wastewater.
AB  - Biochar is an excellent absorbent for most heavy metal ions and organic
      pollutants with high specific surface area, strong aperture structure, high
      stability, higher cation exchange capacity and rich surface functional groups. To
      improve the selective adsorption capacity of biochar to designated heavy metal
      ions, biochar prepared by agricultural waste is modified via Ionic-Imprinted
      Technique. Fourier transform infrared (FT-IR) spectra analysis and X-ray
      photoelectron spectroscopy (XPS) analysis of imprinted biochar (IB) indicate that
      3-Mercaptopropyltrimethoxysilane is grafted on biochar surface through Si-O-Si
      bonds. The results of adsorption experiments indicate that the suitable pH range
      is about 3.0-8.0, the dosage is 2.0 g.L-1, and the adsorption equilibrium is
      reached within 960 min. In addition, the data match pseudo-second-order kinetic
      model and Langmuir model well. The computation results of adsorption
      thermodynamics and stoichiometric displacement theory of adsorption (SDT-A) prove
      that the adsorption process is spontaneous and endothermic. Finally, IB possesses
      a higher selectivity adsorption to Cd(II) and a better reuse capacity. The
      functionalized biochar could solidify designated ions stably.

PMID- 29443955
TI  - Exploration and Exploitation of Novel SSR Markers for Candidate Transcription
      Factor Genes in Lilium Species.
AB  - Lilies (Lilium sp.) are commercially important horticultural crops widely
      cultivated for their flowers and bulbs. Here, we conducted large-scale data
      mining of the lily transcriptome to develop transcription factor (TF)-associated
      microsatellite markers (TFSSRs). Among 216,768 unigenes extracted from our
      sequence data, 6966 unigenes harbored simple sequence repeats (SSRs). Seventy-one
      SSRs were associated with TF genes, and these were used to design primers and
      validate their potential as markers. These 71 SSRs were accomplished with 31
      transcription factor families; including bHLH, MYB, C2H2, ERF, C3H, NAC, bZIP,
      and so on. Fourteen highly polymorphic SSRs were selected based on Polymorphic
      Information Content (PIC) values and used to study genetic diversity and
      population structure in lily accessions. Higher genetic diversity was observed in
      Longiflorum compared to Oriental and Asiatic populations. Lily accessions were
      divided into three sub-populations based in our structure analysis, and an un
      rooted neighbor-joining tree effectively separated the accessions according to
      Asiatic, Oriental, and Longiflorum subgroups. Finally, we showed that 46 of the
      SSR-associated genes were differentially expressed in response to
      Botrytiselliptica infection. Thus, our newly developed TFSSR markers represent a
      powerful tool for large-scale genotyping, high-density and comparative mapping,
      marker-aided backcrossing, and molecular diversity analysis of Lilium sp.

PMID- 29443956
TI  - Gold and Nickel Extended Thiophenic-TTF Bisdithiolene Complexes.
AB  - Gold and nickel bisdithiolene complexes with methyl and tert-butyl substituted
      thiophenetetrathiafulavalenedithiolate ligands (alpha-mtdt and alpha-tbtdt) were
      prepared and characterized. These complexes were obtained, under anaerobic
      conditions, as tetrabutylammonium salts. The diamagnetic gold monoanion (n
      Bu4N)[Au(alpha-mtdt)2] (3) and nickel dianionic species (n-Bu4N)x[Ni(alpha
      mtdt)2] (x = 1,2) (4) were similar to the related non-substituted extended
      thiophenic-TTF (TTF = tetrathiafulvalene) bisdithiolenes. However the
      introduction of the large, bulky substituent tert-butyl, led to the formation of
      a Au (I) dinuclear complex, (n-Bu4N)2[Au2(alpha-tbtdt)2] (5). The neutral methyl
      substituted gold and nickel complexes were easily obtained through air or iodine
      exposure as polycrystalline or amorphous fine powder. [Au(alpha-mtdt)2] (6) and
      [Ni(alpha-mtdt)2] (7) polycrystalline samples display properties of a metallic
      system with a room temperature electrical conductivity of 0.32 S/cm and ~4 S/cm
      and a thermoelectric power of ~5 uV/K and ~32 uV/K, respectively. While [Au(alpha
      mtdt)2] (6) presented a Pauli-like magnetic susceptibility typical of conducting
      systems, in [Ni(alpha-mtdt)2] (7) large magnetic susceptibilities indicative of
      high spin states were observed. Both electric transport properties and magnetic
      properties for gold and nickel [M(alpha-mtdt)2] are indicative that these
      compounds are single component molecular conductors.

PMID- 29443957
TI  - Bone Cement-Augmented Short-Segment Pedicle Screw Fixation for Kummell Disease
      with Spinal Canal Stenosis.
AB  - BACKGROUND This study aimed to explore the feasibility and efficacy of bone
      cement-augmented short-segmental pedicle screw fixation in treating Kummell
      disease. MATERIAL AND METHODS From June 2012 to June 2015, 18 patients with
      Kummell disease with spinal canal stenosis were enrolled in this study. Each
      patient was treated with bone cement-augmented short-segment fixation and
      posterolateral bone grafting, and posterior decompression was performed when
      needed. All patients were followed up for 12-36 months. We retrospectively
      reviewed outcomes, including the Oswestry disability index (ODI), visual analog
      scale (VAS) score, anterior and posterior heights of fractured vertebrae,
      kyphotic Cobb angle, and neurological function by Frankel classification. RESULTS
      The VAS grades, ODI scores, anterior heights of affected vertebrae, and kyphotic
      Cobb angles showed statistically significant differences between pre- and
      postoperative and between preoperative and final follow-up values (P<0.05),
      whereas the differences between postoperative and final follow-up values were not
      statistically significant (P>0.05). The differences between posterior vertebral
      heights at each time point were not statistically significant (P>0.05). Improved
      neurological function was observed in 12 cases at final follow-up. Three cases
      had complications, including asymptomatic cement leakage in 2 patients and
      delayed wound infection in 1 patient. CONCLUSIONS Bone cement-augmented short
      segment pedicle screw fixation is safe and effective for treating Kummell
      disease, and can achieve satisfactory correction of kyphosis and vertebral
      height, with pain relief and improvement in neurological function, with few
      complications.

PMID- 29443958
TI  - Tissue stiffening coordinates morphogenesis by triggering collective cell
      migration in vivo.
AB  - Collective cell migration is essential for morphogenesis, tissue remodelling and
      cancer invasion. In vivo, groups of cells move in an orchestrated way through
      tissues. This movement involves mechanical as well as molecular interactions
      between cells and their environment. While the role of molecular signals in
      collective cell migration is comparatively well understood, how tissue mechanics
      influence collective cell migration in vivo remains unknown. Here we investigated
      the importance of mechanical cues in the collective migration of the Xenopus
      laevis neural crest cells, an embryonic cell population whose migratory behaviour
      has been likened to cancer invasion. We found that, during morphogenesis, the
      head mesoderm underlying the cephalic neural crest stiffens. This stiffening
      initiates an epithelial-to-mesenchymal transition in neural crest cells and
      triggers their collective migration. To detect changes in their mechanical
      environment, neural crest cells use mechanosensation mediated by the integrin
      vinculin-talin complex. By performing mechanical and molecular manipulations, we
      show that mesoderm stiffening is necessary and sufficient to trigger neural crest
      migration. Finally, we demonstrate that convergent extension of the mesoderm,
      which starts during gastrulation, leads to increased mesoderm stiffness by
      increasing the cell density underneath the neural crest. These results show that
      convergent extension of the mesoderm has a role as a mechanical coordinator of
      morphogenesis, and reveal a link between two apparently unconnected processes
      gastrulation and neural crest migration-via changes in tissue mechanics. Overall,
      we demonstrate that changes in substrate stiffness can trigger collective cell
      migration by promoting epithelial-to-mesenchymal transition in vivo. More
      broadly, our results raise the idea that tissue mechanics combines with molecular
      effectors to coordinate morphogenesis.

PMID- 29443959
TI  - Transcriptional regulation by NR5A2 links differentiation and inflammation in the
      pancreas.
AB  - Chronic inflammation increases the risk of developing one of several types of
      cancer. Inflammatory responses are currently thought to be controlled by
      mechanisms that rely on transcriptional networks that are distinct from those
      involved in cell differentiation. The orphan nuclear receptor NR5A2 participates
      in a wide variety of processes, including cholesterol and glucose metabolism in
      the liver, resolution of endoplasmic reticulum stress, intestinal glucocorticoid
      production, pancreatic development and acinar differentiation. In genome-wide
      association studies, single nucleotide polymorphisms in the vicinity of NR5A2
      have previously been associated with the risk of pancreatic adenocarcinoma. In
      mice, Nr5a2 heterozygosity sensitizes the pancreas to damage, impairs
      regeneration and cooperates with mutant Kras in tumour progression. Here, using a
      global transcriptomic analysis, we describe an epithelial-cell-autonomous basal
      pre-inflammatory state in the pancreas of Nr5a2+/- mice that is reminiscent of
      the early stages of pancreatitis-induced inflammation and is conserved in
      histologically normal human pancreases with reduced expression of NR5A2 mRNA. In
      Nr5a2+/-mice, NR5A2 undergoes a marked transcriptional switch, relocating from
      differentiation-specific to inflammatory genes and thereby promoting gene
      transcription that is dependent on the AP-1 transcription factor. Pancreatic
      deletion of Jun rescues the pre-inflammatory phenotype, as well as binding of
      NR5A2 to inflammatory gene promoters and the defective regenerative response to
      damage. These findings support the notion that, in the pancreas, the
      transcriptional networks involved in differentiation-specific functions also
      suppress inflammatory programmes. Under conditions of genetic or environmental
      constraint, these networks can be subverted to foster inflammation.

PMID- 29443961
TI  - A coherent spin-photon interface in silicon.
AB  - Electron spins in silicon quantum dots are attractive systems for quantum
      computing owing to their long coherence times and the promise of rapid scaling of
      the number of dots in a system using semiconductor fabrication techniques.
      Although nearest-neighbour exchange coupling of two spins has been demonstrated,
      the interaction of spins via microwave-frequency photons could enable long
      distance spin-spin coupling and connections between arbitrary pairs of qubits
      ('all-to-all' connectivity) in a spin-based quantum processor. Realizing coherent
      spin-photon coupling is challenging because of the small magnetic-dipole moment
      of a single spin, which limits magnetic-dipole coupling rates to less than 1
      kilohertz. Here we demonstrate strong coupling between a single spin in silicon
      and a single microwave-frequency photon, with spin-photon coupling rates of more
      than 10 megahertz. The mechanism that enables the coherent spin-photon
      interactions is based on spin-charge hybridization in the presence of a magnetic
      field gradient. In addition to spin-photon coupling, we demonstrate coherent
      control and dispersive readout of a single spin. These results open up a direct
      path to entangling single spins using microwave-frequency photons.

PMID- 29443960
TI  - TGFbeta attenuates tumour response to PD-L1 blockade by contributing to exclusion
      of T cells.
AB  - Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death
      ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with
      various cancers, including metastatic urothelial cancer. However, these responses
      only occur in a subset of patients. Elucidating the determinants of response and
      resistance is key to improving outcomes and developing new treatment strategies.
      Here we examined tumours from a large cohort of patients with metastatic
      urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and
      identified major determinants of clinical outcome. Response to treatment was
      associated with CD8+ T-effector cell phenotype and, to an even greater extent,
      high neoantigen or tumour mutation burden. Lack of response was associated with a
      signature of transforming growth factor beta (TGFbeta) signalling in fibroblasts.
      This occurred particularly in patients with tumours, which showed exclusion of
      CD8+ T cells from the tumour parenchyma that were instead found in the fibroblast
      and collagen-rich peritumoural stroma; a common phenotype among patients with
      metastatic urothelial cancer. Using a mouse model that recapitulates this immune
      excluded phenotype, we found that therapeutic co-administration of TGFbeta
      blocking and anti-PD-L1 antibodies reduced TGFbeta signalling in stromal cells,
      facilitated T-cell penetration into the centre of tumours, and provoked vigorous
      anti-tumour immunity and tumour regression. Integration of these three
      independent biological features provides the best basis for understanding patient
      outcome in this setting and suggests that TGFbeta shapes the tumour
      microenvironment to restrain anti-tumour immunity by restricting T-cell
      infiltration.

PMID- 29443963
TI  - Erratum: Measurement of the multi-TeV neutrino interaction cross-section with
      IceCube using Earth absorption.
AB  - This corrects the article DOI: 10.1038/nature24459.

PMID- 29443962
TI  - A programmable two-qubit quantum processor in silicon.
AB  - Now that it is possible to achieve measurement and control fidelities for
      individual quantum bits (qubits) above the threshold for fault tolerance,
      attention is moving towards the difficult task of scaling up the number of
      physical qubits to the large numbers that are needed for fault-tolerant quantum
      computing. In this context, quantum-dot-based spin qubits could have substantial
      advantages over other types of qubit owing to their potential for all-electrical
      operation and ability to be integrated at high density onto an industrial
      platform. Initialization, readout and single- and two-qubit gates have been
      demonstrated in various quantum-dot-based qubit representations. However, as seen
      with small-scale demonstrations of quantum computers using other types of qubit,
      combining these elements leads to challenges related to qubit crosstalk, state
      leakage, calibration and control hardware. Here we overcome these challenges by
      using carefully designed control techniques to demonstrate a programmable two
      qubit quantum processor in a silicon device that can perform the Deutsch-Josza
      algorithm and the Grover search algorithm-canonical examples of quantum
      algorithms that outperform their classical analogues. We characterize the
      entanglement in our processor by using quantum-state tomography of Bell states,
      measuring state fidelities of 85-89 per cent and concurrences of 73-82 per cent.
      These results pave the way for larger-scale quantum computers that use spins
      confined to quantum dots.

PMID- 29443966
TI  - Global patterns of tropical forest fragmentation.
AB  - Remote sensing enables the quantification of tropical deforestation with high
      spatial resolution. This in-depth mapping has led to substantial advances in the
      analysis of continent-wide fragmentation of tropical forests. Here we identified
      approximately 130 million forest fragments in three continents that show
      surprisingly similar power-law size and perimeter distributions as well as
      fractal dimensions. Power-law distributions have been observed in many natural
      phenomena such as wildfires, landslides and earthquakes. The principles of
      percolation theory provide one explanation for the observed patterns, and suggest
      that forest fragmentation is close to the critical point of percolation;
      simulation modelling also supports this hypothesis. The observed patterns emerge
      not only from random deforestation, which can be described by percolation theory,
      but also from a wide range of deforestation and forest-recovery regimes. Our
      models predict that additional forest loss will result in a large increase in the
      total number of forest fragments-at maximum by a factor of 33 over 50 years-as
      well as a decrease in their size, and that these consequences could be partly
      mitigated by reforestation and forest protection.

PMID- 29443965
TI  - A molecular atlas of cell types and zonation in the brain vasculature.
AB  - Cerebrovascular disease is the third most common cause of death in developed
      countries, but our understanding of the cells that compose the cerebral
      vasculature is limited. Here, using vascular single-cell transcriptomics, we
      provide molecular definitions for the principal types of blood vascular and
      vessel-associated cells in the adult mouse brain. We uncover the transcriptional
      basis of the gradual phenotypic change (zonation) along the arteriovenous axis
      and reveal unexpected cell type differences: a seamless continuum for endothelial
      cells versus a punctuated continuum for mural cells. We also provide insight into
      pericyte organotypicity and define a population of perivascular fibroblast-like
      cells that are present on all vessel types except capillaries. Our work
      illustrates the power of single-cell transcriptomics to decode the higher
      organizational principles of a tissue and may provide the initial chapter in a
      molecular encyclopaedia of the mammalian vasculature.

PMID- 29443968
TI  - Retraction: Asia's glaciers are a regionally important buffer against drought.
AB  - This corrects the article DOI: 10.1038/nature22062.

PMID- 29443964
TI  - TGFbeta drives immune evasion in genetically reconstituted colon cancer
      metastasis.
AB  - Most patients with colorectal cancer die as a result of the disease spreading to
      other organs. However, no prevalent mutations have been associated with
      metastatic colorectal cancers. Instead, particular features of the tumour
      microenvironment, such as lack of T-cell infiltration, low type 1 T-helper cell
      (TH1) activity and reduced immune cytotoxicity or increased TGFbeta levels
      predict adverse outcomes in patients with colorectal cancer. Here we analyse the
      interplay between genetic alterations and the tumour microenvironment by crossing
      mice bearing conditional alleles of four main colorectal cancer mutations in
      intestinal stem cells. Quadruple-mutant mice developed metastatic intestinal
      tumours that display key hallmarks of human microsatellite-stable colorectal
      cancers, including low mutational burden, T-cell exclusion and TGFbeta-activated
      stroma. Inhibition of the PD-1-PD-L1 immune checkpoint provoked a limited
      response in this model system. By contrast, inhibition of TGFbeta unleashed a
      potent and enduring cytotoxic T-cell response against tumour cells that prevented
      metastasis. In mice with progressive liver metastatic disease, blockade of
      TGFbeta signalling rendered tumours susceptible to anti-PD-1-PD-L1 therapy. Our
      data show that increased TGFbeta in the tumour microenvironment represents a
      primary mechanism of immune evasion that promotes T-cell exclusion and blocks
      acquisition of the TH1-effector phenotype. Immunotherapies directed against
      TGFbeta signalling may therefore have broad applications in treating patients
      with advanced colorectal cancer.

PMID- 29443967
TI  - Peptidoglycan synthesis drives an FtsZ-treadmilling-independent step of
      cytokinesis.
AB  - Peptidoglycan is the main component of the bacterial wall and protects cells from
      the mechanical stress that results from high intracellular turgor. Peptidoglycan
      biosynthesis is very similar in all bacteria; bacterial shapes are therefore
      mainly determined by the spatial and temporal regulation of peptidoglycan
      synthesis rather than by the chemical composition of peptidoglycan. The form of
      rod-shaped bacteria, such as Bacillus subtilis or Escherichia coli, is generated
      by the action of two peptidoglycan synthesis machineries that act at the septum
      and at the lateral wall in processes coordinated by the cytoskeletal proteins
      FtsZ and MreB, respectively. The tubulin homologue FtsZ is the first protein
      recruited to the division site, where it assembles in filaments-forming the Z
      ring-that undergo treadmilling and recruit later divisome proteins. The rate of
      treadmilling in B. subtilis controls the rates of both peptidoglycan synthesis
      and cell division. The actin homologue MreB forms discrete patches that move
      circumferentially around the cell in tracks perpendicular to the long axis of the
      cell, and organize the insertion of new cell wall during elongation. Cocci such
      as Staphylococcus aureus possess only one type of peptidoglycan synthesis
      machinery, which is diverted from the cell periphery to the septum in preparation
      for division. The molecular cue that coordinates this transition has remained
      elusive. Here we investigate the localization of S. aureus peptidoglycan
      biosynthesis proteins and show that the recruitment of the putative lipid II
      flippase MurJ to the septum, by the DivIB-DivIC-FtsL complex, drives
      peptidoglycan incorporation to the midcell. MurJ recruitment corresponds to a
      turning point in cytokinesis, which is slow and dependent on FtsZ treadmilling
      before MurJ arrival but becomes faster and independent of FtsZ treadmilling after
      peptidoglycan synthesis activity is directed to the septum, where it provides
      additional force for cell envelope constriction.

PMID- 29443969
TI  - Corrigendum: Immune evasion of Plasmodium falciparum by RIFIN via inhibitory
      receptors.
AB  - This corrects the article DOI: 10.1038/nature24994.

PMID- 29443971
TI  - Light-activated chemical probing of nucleobase solvent accessibility inside
      cells.
AB  - This corrects the article DOI: 10.1038/nchembio.2548.

PMID- 29443970
TI  - Structural and evolutionary insights into ribosomal RNA methylation.
AB  - Methylation of nucleotides in ribosomal RNAs (rRNAs) is a ubiquitous feature that
      occurs in all living organisms. Identification of all enzymes responsible for
      rRNA methylation, as well as mapping of all modified rRNA residues, is now
      complete for a number of model species, such as Escherichia coli and
      Saccharomyces cerevisiae. Recent high-resolution structures of bacterial
      ribosomes provided the first direct visualization of methylated nucleotides. The
      structures of ribosomes from various organisms and organelles have also lately
      become available, enabling comparative structure-based analysis of rRNA
      methylation sites in various taxonomic groups. In addition to the conserved core
      of modified residues in ribosomes from the majority of studied organisms,
      structural analysis points to the functional roles of some of the rRNA
      methylations, which are discussed in this Review in an evolutionary context.

PMID- 29443972
TI  - The ABCs of PTMs.

PMID- 29443973
TI  - RNA structure: A LASER-focused view into cells.

PMID- 29443974
TI  - Covalent modifications of polysaccharides in mycobacteria.

PMID- 29443975
TI  - Features and regulation of non-enzymatic post-translational modifications.
AB  - Non-enzymatic post-translational modifications of proteins can occur when a
      nucleophilic or redox-sensitive amino acid side chain encounters a reactive
      metabolite. In many cases, the biological function of these modifications is
      limited by their irreversibility, and consequently these non-enzymatic
      modifications are often considered as indicators of stress and disease. Certain
      non-enzymatic post-translational modifications, however, can be reversed, which
      provides an additional layer of regulation and renders these modifications
      suitable for controlling a diverse set of cellular processes ranging from
      signaling to metabolism. Here we summarize recent examples of irreversible and
      reversible non-enzymatic modifications, with an emphasis on the latter category.
      We use two examples, lysine glutarylation and pyrophosphorylation, to highlight
      principles of the regulation of reversible non-enzymatic post-translational
      modifications in more detail. Overall, a picture emerges that goes well beyond
      nonspecific chemical reactions and cellular damage, and instead portrays
      multifaceted functions of non-enzymatic post-translational modifications.

PMID- 29443977
TI  - Protein evolution: Hacking an enzyme.

PMID- 29443979
TI  - GPCR: Lock and key become flexible.

PMID- 29443978
TI  - Distinguishing RNA modifications from noise in epitranscriptome maps.
AB  - Messenger RNA (mRNA) and long noncoding RNA (lncRNA) can be subjected to a
      variety of post-transcriptional modifications that markedly influence their fate
      and function. This concept of 'epitranscriptomic' modifications and the
      understanding of their function has been driven by new technologies for
      transcriptome-wide mapping of modified nucleotides using next-generation
      sequencing. Mapping technologies have successfully documented the location and
      prevalence of several modified nucleotides in the transcriptome. However, some
      mapping methods have led to proposals of pervasive novel RNA modifications that
      have subsequently been shown to be exceptionally rare. These controversies have
      resulted in confusion about the identity of the modified nucleotides comprising
      the epitranscriptome in mRNA and lncRNA. Here we discuss the different
      transcriptome-wide technologies for mapping modified nucleotides. We describe why
      these methods can have poor accuracy and specificity. Finally, we describe
      emerging strategies that minimize false positives and other pitfalls associated
      with mapping and measuring epitranscriptomic modifications.

PMID- 29443980
TI  - Glycosylation: Gluing on glycans.

PMID- 29443981
TI  - Viruses: Capsids under pressure.

PMID- 29443976
TI  - How many human proteoforms are there?
AB  - Despite decades of accumulated knowledge about proteins and their post
      translational modifications (PTMs), numerous questions remain regarding their
      molecular composition and biological function. One of the most fundamental
      queries is the extent to which the combinations of DNA-, RNA- and PTM-level
      variations explode the complexity of the human proteome. Here, we outline what we
      know from current databases and measurement strategies including mass
      spectrometry-based proteomics. In doing so, we examine prevailing notions about
      the number of modifications displayed on human proteins and how they combine to
      generate the protein diversity underlying health and disease. We frame central
      issues regarding determination of protein-level variation and PTMs, including
      some paradoxes present in the field today. We use this framework to assess
      existing data and to ask the question, "How many distinct primary structures of
      proteins (proteoforms) are created from the 20,300 human genes?" We also explore
      prospects for improving measurements to better regularize protein-level biology
      and efficiently associate PTMs to function and phenotype.

PMID- 29443982
TI  - Lipids: Picturing palmitoylation.

PMID- 29443983
TI  - Ubiquitination: Trashing the CIA.

PMID- 29443984
TI  - Synthetic biology: Reframing cell therapy for cancer.

PMID- 29443985
TI  - Altering form for function.

PMID- 29443987
TI  - Long-distance thermal temporal ghost imaging over optical fibers.
AB  - A thermal ghost imaging scheme between two distant parties is proposed and
      experimentally demonstrated over long-distance optical fibers. In the scheme, the
      weak thermal light is split into two paths. Photons in one path are spatially
      diffused according to their frequencies by a spatial dispersion component, then
      illuminate the object and record its spatial transmission information. Photons in
      the other path are temporally diffused by a temporal dispersion component. By the
      coincidence measurement between photons of two paths, the object can be imaged in
      a way of ghost imaging, based on the frequency correlation between photons in the
      two paths. In the experiment, the weak thermal light source is prepared by the
      spontaneous four-wave mixing in a silicon waveguide. The temporal dispersion is
      introduced by single-mode fibers of 50 km, which also could be looked at as a
      fiber link. Experimental results show that this scheme can be realized over long
      distance optical fibers.

PMID- 29443988
TI  - Quantitative imaging of anisotropic material properties with vectorial
      ptychography.
AB  - Following the recent establishment of the formalism of vectorial ptychography
      [Opt. Lett.40, 5144 (2015)OPLEDP0146-959210.1364/OL.40.005144], first
      measurements, to the best of our knowledge, are reported in the optical range,
      demonstrating the capability of the proposed method to map the four parameters of
      the Jones matrix of an anisotropic specimen, and therefore to quantify a wide
      range of optical material properties, including power transmittance, optical path
      difference, diattenuation, retardance, and fast-axis orientation.

PMID- 29443986
TI  - Insights into the biogenesis, function, and regulation of ADP-ribosylation.
AB  - ADP-ribosylation-the transfer of ADP-ribose (ADPr) from NAD+ onto target
      molecules-is catalyzed by members of the ADP-ribosyltransferase (ART) superfamily
      of proteins, found in all kingdoms of life. Modification of amino acids in
      protein targets by ADPr regulates critical cellular pathways in eukaryotes and
      underlies the pathogenicity of certain bacteria. Several members of the ART
      superfamily are highly relevant for disease; these include the poly(ADP-ribose)
      polymerases (PARPs), recently shown to be important cancer targets, and the
      bacterial toxins diphtheria toxin and cholera toxin, long known to be responsible
      for the symptoms of diphtheria and cholera that result in morbidity. In this
      Review, we discuss the functions of amino acid ADPr modifications and the ART
      proteins that make them, the nature of the chemical linkage between ADPr and its
      targets and how this impacts function and stability, and the way that ARTs select
      specific amino acids in targets to modify.

PMID- 29443989
TI  - Optical see-through Maxwellian near-to-eye display with an enlarged eyebox.
AB  - We propose a Maxwellian near-to-eye display implemented using a multiplexed
      holographic optical element. Maxwellian configuration removes the focal cue of
      the displayed virtual image completely, presenting an always-focused image to the
      observer regardless of the focal length of the eye. The transparent property of
      the holographic optical element enables the optical see-through feature, making
      the proposed near-to-eye display suitable for augmented reality applications. The
      multiplexing of multiple concave mirrors into a single holographic optical
      element enlarges the effective eyebox, relaxing the limitation of the
      conventional Maxwellian displays. Optical experiment confirms that the proposed
      display can present always-focused images on top of the real environment with 9.2
      degrees (H)*5.2 degrees (V) field of view, and 9  mm (H)*3  mm (V) eyebox.

PMID- 29443990
TI  - Photonic hook: a new curved light beam.
AB  - It is well known that electromagnetic radiation propagates along a straight line,
      but this common sense was broken by the artificial curved light-the Airy beam. In
      this Letter, we demonstrate a new type of curved light beam besides the Airy
      beam, the so-called "photonic hook." This photonic hook is a curved high
      intensity focus by a dielectric trapezoid particle illuminated by a plane wave.
      The difference between the phase velocity and the interference of the waves
      inside the particle causes the phenomenon of focus bending.

PMID- 29443991
TI  - Ultrasound detection at fiber end-facets with surface plasmon resonance cavities.
AB  - Ultrasound detection is performed by measuring laser reflection off a surface
      plasmon resonance cavity which is integrated at a single-mode fiber end facet. It
      shows a total noise (or laser RIN) equivalent pressure of 9.7 KPa (or 5.2 KPa)
      over 0-20 MHz, a 6-dB angular detection range as large as 70 degrees  near 10
      MHz, a detection bandwidth larger than 125 MHz, and a stable performance for over
      20 min without feedback in ambient conditions. Its small form factor, fiber-optic
      integration, almost omnidirectional responsivity and large bandwidth are
      favorable for in vivo applications and high resolution imaging.

PMID- 29443992
TI  - Spectral asymmetries in the resonance fluorescence of two-level systems under
      pulsed excitation.
AB  - We present an open-system master equation study of the coherent and incoherent
      resonance fluorescence spectrum from a two-level quantum system under coherent
      pulsed excitation. Several pronounced features that differ from the fluorescence
      under a constant drive are highlighted, including a multi-peak structure and a
      pronounced off-resonant spectral asymmetry, in stark contrast to the conventional
      symmetrical Mollow triplet. We also study semiconductor quantum dot systems using
      a polaron master equation and show how the key features of dynamic resonance
      fluorescence change with electron-acoustic-phonon coupling.

PMID- 29443993
TI  - Terahertz-based retrieval of the spectral phase and amplitude of ultrashort laser
      pulses.
AB  - Terahertz (THz) radiation is of great interest for a variety of applications,
      e.g., particle accelerations, spectroscopy investigations of quantum systems, and
      high-field study of materials. One of the most common laser-based processes to
      produce THz pulses is optical rectification, which transduces an infrared pump
      laser to the THz domain (0.1-20 THz). In this work, we propose and theoretically
      describe a method to characterize the amplitude and phase of the electric field
      of the pump laser pulse relying on THz generation and detection. We demonstrate
      with a numerical example how THz radiation can be used as diagnostics to
      characterize laser pulses with temporal length at the femtosecond level.

PMID- 29443994
TI  - Adaptive pumping for spectral control of broadband second-harmonic generation.
AB  - Second-harmonic generation (SHG) is always a significant frequency conversion
      process in nonlinear optics for many great applications but can be limited when
      broadband spectral laser sources are involved, e.g., femtosecond pulses. The
      conversion efficiency can be high, but the spectral control is hard because of
      the phase-matching (PM) limitation. Recently, a random quasi-phase-matching (QPM)
      scheme was proposed to make use of highly nonlinear materials that are difficult
      to be phase matched under traditional configurations. The spectral control is
      even harder in anisotropic random materials, and the coherence is completely
      lost. Here, we proposed an approach to solve this problem by coherent light
      control via feedback-based wavefront shaping. We utilized this method for
      spectral control of broadband SHG, which can be efficient even in strongly
      scattering media. Randomly selected wavelengths in the broadband spectra were
      enhanced with a good selectivity, and the direction was also controlled in a
      three-dimensional (3D) configuration. This technique paves the way for convenient
      spatial and spectral control of both linear and nonlinear emissions and a local
      enhancement of their conversion efficiency, indicating great progress in both
      random and ultrafast nonlinear optics.

PMID- 29443995
TI  - Evanescent field refractometry in planar optical fiber.
AB  - This Letter demonstrates a refractometer in integrated optical fiber, a new
      optical platform that planarizes fiber using flame hydrolysis deposition (FHD).
      The unique advantage of the technology is survivability in harsh environments.
      The platform is mechanically robust, and can survive elevated temperatures
      approaching 1000 degrees C and exposure to common solvents, including acetone,
      gasoline, and methanol. For the demonstrated refractometer, fabrication was
      achieved through wet etching an SMF-28 fiber to a diameter of 8 MUm before FHD
      planarization. An external refractive index was monitored using fiber Bragg
      gratings (FBGs), written into the core of the planarized fiber. A direct
      comparison to alternative FBG refractometers is made, for which the developed
      platform is shown to have comparable sensitivity, with the added advantage of
      survivability in harsh environments.

PMID- 29443996
TI  - Suspended silicon waveguides for long-wave infrared wavelengths.
AB  - In this Letter, we report suspended silicon waveguides operating at a wavelength
      of 7.67 MUm with a propagation loss of 3.1+/-0.3  dB/cm. To our knowledge, this
      is the first demonstration of low-loss silicon waveguides at such a long
      wavelength, with loss comparable to other platforms that use more exotic
      materials. The suspended Si waveguide core is supported by a sub-wavelength
      grating that provides lateral optical confinement while also allowing access to
      the buried oxide layer so that it can be wet etched using hydrofluoric acid. We
      also demonstrate low-loss waveguide bends and s-bends.

PMID- 29443997
TI  - Ultra-low-threshold InGaN/GaN quantum dot micro-ring lasers.
AB  - In this work, we demonstrate ultra-low-threshold, optically pumped, room
      temperature lasing in GaN microdisk and micro-ring cavities containing InGaN
      quantum dots and fragmented quantum wells, with the lowest measured threshold at
      a record low of 6.2  MUJ/cm2. When pump volume decreases, we observe a systematic
      decrease in the lasing threshold of micro-rings. The photon loss rate, gamma,
      increases with increasing inner ring diameter, leading to a systematic decrease
      in the post-threshold slope efficiency, while the quality factor of the lasing
      mode remains largely unchanged. A careful analysis using finite-difference time
      domain simulations attributes the increased gamma to the loss of photons from
      lower-quality higher-order modes during amplified spontaneous emission.

PMID- 29443998
TI  - Phase conjugate digital inline holography (PCDIH).
AB  - Digital inline holography (DIH) provides instantaneous three-dimensional (3D)
      measurements of diffracting objects; however, phase disturbances in the beam path
      can distort the imaging. In this Letter, a phase conjugate digital inline
      holography (PCDIH) configuration is proposed for removal of phase disturbances.
      Brillouin-enhanced four-wave mixing produces a phase conjugate signal that back
      propagates along the DIH beam path. The results demonstrate the removal of
      distortions caused by gas-phase shocks to recover 3D images of diffracting
      objects.

PMID- 29443999
TI  - Absolute distance measurement by multi-heterodyne interferometry using an electro
      optic triple comb.
AB  - We experimentally demonstrate a method for absolute distance measurement using a
      triple-comb-based multi-heterodyne interferometer which has the capacity to
      simultaneously balance the non-ambiguous range, resolution, update rate, and
      cost. Three flat-top electro-optic combs generated via cascaded intensity and
      phase modulators are adopted to form a measurement scheme including rough and
      fine measurements, and the unknown distance is determined by detecting the phase
      changes of the consecutive synthetic wavelengths. Experimental results
      demonstrate an agreement within 750 nm over 80 m distance at an update rate of
      167 MUs.

PMID- 29444000
TI  - Reducing Rowland ghosts in diffraction gratings by dynamic exposure near-field
      holography.
AB  - Near-field holography (NFH) combined with electron beam lithography (EBL)-written
      phase masks is a promising method for the rapid realization of diffraction
      gratings with high resolution and high accuracy in line density distribution. We
      demonstrate a dynamic exposure method in which the grating substrate is shifted
      during pattern transfer. This reduces the effects of stitching errors, resulting
      in the decreased intensity of the optical stray light (i.e., Rowland ghosts). We
      demonstrate the intensity suppression of ghosts by 60%. This illustrates the
      potential for dynamic NFH to suppress undesirable periodic patterns from phase
      masks and alleviate the stitching errors induced by EBL.

PMID- 29444001
TI  - Effective suppression of residual coherent phase error in a dual-polarization
      fiber optic gyroscope.
AB  - The impact of residual coherent phase error in a dual-polarization
      interferometric fiber optic gyroscope (IFOG) is investigated. Although it has
      been intuitively assumed that the coherence of a light source can be eliminated
      by a sufficient long fiber delay, the experiment and theory indicate that it
      still contributes a remarkable portion to long-term instability. After the
      residual coherent phase error is well handled, we demonstrate a dual-polarization
      IFOG with bias instability of 3.56*10-4 degrees /h. Comparisons show that such
      performance is even better than the conventional "minimal scheme" that operates
      on one polarization.

PMID- 29444002
TI  - Analytical model of waveform-controlled single-cycle light pulses from an
      undulator.
AB  - This Letter builds upon a recent concept [Phys. Rev. Lett.113, 104801
      (2014)PRLTAO0031-900710.1103/PhysRevLett.113.104801] for producing ultrashort
      optical pulses through the coherent radiation of electrons in an undulator. Each
      pulse contains only a single oscillation cycle, and has a controlled waveform
      (and hence a stable carrier-envelope phase). While the concept had been
      demonstrated numerically, this Letter provides an analytical model for the
      radiation mechanism, thereby revealing three key observations: (i) the
      correlation between the waveforms of the optical and undulator fields; (ii) the
      free-space dispersion of transversely confined light; and (iii) the dependence of
      the optical pulse shape on the undulator field strength.

PMID- 29444003
TI  - Measurement of the topological charge and index of vortex vector optical fields
      with a space-variant half-wave plate.
AB  - Vortex vector optical fields (VVOFs) refer to a kind of vector optical field with
      an azimuth-variant polarization and a helical phase, simultaneously. Such a VVOF
      is defined by the topological index of the polarization singularity and the
      topological charge of the phase vortex. We present a simple method to measure the
      topological charge and index of VVOFs by using a space-variant half-wave plate
      (SV-HWP). The geometric phase grating of the SV-HWP diffracts a VVOF into +/-1
      orders with orthogonally left- and right-handed circular polarizations. By
      inserting a polarizer behind the SV-HWP, the two circular polarization states
      project into the linear polarization and then interfere with each other to form
      the interference pattern, which enables the direct measurement of the topological
      charge and index of VVOFs.

PMID- 29444004
TI  - Demonstration of a thermo-optic phase shifter by utilizing high-Q resonance in
      high-index-contrast grating.
AB  - A thermo-optic phase shifter is proposed and demonstrated by utilizing the high-Q
      resonance in high-index-contrast grating (HCG). The Q-factor up to ~12000 is
      measured in a footprint of 110  MUm*300  MUm. By heating the HCG with paired
      metal strip micro-heaters, the optical resonance shifts, which induces phase
      modulation. A phase shift of ~1.2pi under heating power of ~32  mW is directly
      observed and demodulated from the fringes shifting in a Michelson interferometer.
      The proposed configuration can also be extended to realize high-speed phase shift
      by adopting electro-optical modulation.

PMID- 29444005
TI  - Single-pulse writing of a concave microlens array.
AB  - This work developed a method of femtosecond laser (fs-laser) parallel processing
      assisted by wet etching to fabricate 3D micro-optical components. A 2D fs-laser
      spot array with designed spatial distribution was generated by a spatial light
      modulator. A single-pulse exposure of the entire array was used for parallel
      processing. By subsequent wet etching, a close-packed hexagonal arrangement, 3D
      concave microlens array on a curved surface with a radius of approximately 120
      MUm was fabricated, each unit lens of which has designable spatial distribution.
      Characterization of imaging was carried out by a microscope and showed a unique
      imaging property in multi-planes. This method provides a parallel and efficient
      technique to fabricate 3D micro-optical devices for applications in optofluidics,
      optical communication, and integrated optics.

PMID- 29444006
TI  - Highly uniform and monodisperse beta-NaYF4 : Sm3+ nanoparticles for a nanoscale
      optical thermometer.
AB  - Monodisperse beta-NaYF4:1%Sm3+ nanoparticles were fabricated successfully via the
      thermal decomposition technique. Strong temperature dependence of the Sm3+
      emission was observed when its thermally populated state H7/26 was directly
      excited to the G5/24 level. This strategy not only can eliminate laser heating
      and background Stokes-type scattering noise but also has a high quantum yield as
      a result of one-photon excitation process. Under 594.0 nm laser excitation, the
      emission intensity of G5/24-H5/26 enhances monotonously with rising temperature
      from 300 K to 430 K, including a physiological temperature range (27 degrees C-60
      degrees C). The relative temperature sensitivity can reach 1.1%   K-1 and 0.91% 
      K-1 at 300 K and 330 K, respectively. In addition, the repeatability of
      temperature sensing was evaluated under several heating-cooling cycles, and the
      decay curves of the emission at 560.0 nm (G5/24-H5/26) at different temperatures
      were also investigated. These results raise the prospects of monodisperse beta
      NaYF4:1%Sm3+ nanoparticles for optical temperature sensing in biomedicine fields.

PMID- 29444007
TI  - Three-dimensional inverse synthetic aperture lidar imaging for long-range
      spinning targets.
AB  - We present a three-dimensional (3D) imaging method for long-range spinning
      targets. This method acquires multi-angle two-dimensional (2D) images of spinning
      targets by the inverse synthetic aperture lidar (ISAL) imaging technique. The 3D
      distribution of the scattering coefficients of a target has a mapping
      relationship with the series of 2D images. This mapping is analyzed, and a 3D
      Hough transform is used to implement inverse mapping. The parameter space of the
      Hough transform is the estimation of the 3D distribution of the scattering
      coefficients. The 3D point spread function obtained by the method has narrow main
      lobe widths and sufficiently low side lobes to achieve high image quality, which
      is verified by computer simulations. In the simulations, the main lobe widths in
      the three dimensions are 0.29 cm, 0.29 cm, and 3.48 cm, respectively. In outdoor
      experiments, 3D images of targets at 1 km away from the lidar were obtained. The
      images clearly show the 3D shape of targets.

PMID- 29444008
TI  - Sensitive measurement of stress birefringence of fused silica substrates with
      cavity ring-down technique.
AB  - A polarized cavity ring-down technique was employed to precisely measure the
      residual stress birefringence of fused silica substrates with greatly enhanced
      measurement sensitivity. Intracavity birefringence resulted in beating of two
      orthogonally resonant modes in a Fabry-Perot cavity. The beating frequency of the
      ring-down decay was directly related to phase retardation induced by stress
      birefringence of optical components inside the cavity. For fused silica
      substrates, measurement reproducibilities of phase retardation of 2.38*10-6  rad
      and of optical path difference of 2.4*10-4  nm were experimentally achieved. In
      addition, spatially resolved mapping of stress birefringence of a fused silica
      substrate was obtained, which was in good agreement with that measured with a
      commercial stress birefringence measurement instrument. The experimental results
      demonstrated that cavity ring-down is a sensitive technique for stress
      birefringence measurements of optical components.

PMID- 29444009
TI  - Ultralow-threshold continuous-wave lasing assisted by a metallic optofluidic
      cavity exploiting continuous pump.
AB  - We report an ultralow-threshold continuous-wave lasing via a metallic optofluidic
      resonant cavity based on the symmetrical metal-cladding waveguide. The high
      quality factor Q and spontaneous emission coupling factor beta of the waveguide
      strengthen the interaction between the gain medium and the ultrahigh order modes
      (UOMs); hence, the room-temperature, narrowband lasing can be effectively pumped
      by a continuous laser of low intensity. Rhodamine 6G and methylene blue are
      chosen to verify the applicability of the proposed concept. Lasing is emitted
      from the chip surface when the pumped laser is well coupled into the UOMs. For
      methylene blue with a concentration of 2.57*10-13  mol/ml, the operated emission
      can be observed with the launched pump threshold as low as 2.1  MUW/cm2.

PMID- 29444010
TI  - 3-bit writing of information in nanoporous glass by a single sub-microsecond
      burst of femtosecond pulses.
AB  - We have found that a single sub-microsecond burst of femtosecond laser pulses
      produces a sub-micrometer cavity possessing the homogeneous birefringence with
      slow-axis orientation perpendicular to polarization of the laser beam in high
      silicate nanoporous glass. Retardance and the root mean square of slow-axis
      orientation are investigated in dependence on the energy and the number of pulses
      in the burst. A burst of just three pulses with 98 ns inter-pulse intervals has
      been shown to induce homogeneous birefringence, and a burst of four pulses has
      provided birefringence with retardance of 35 nm, which is sufficient for reliable
      readout of the information recorded with multilevel encoding in slow-axis
      orientation. A text file has been recorded and read out in an array of
      birefringent cavities, each carrying 3 bits of information. The sub-microsecond
      burst of femtosecond pulses paves the way for a multiple increase of the rate of
      digital information recording with multilevel encoding in glass.

PMID- 29444011
TI  - Complementary metal-oxide semiconductor compatible source of single photons at
      near-visible wavelengths.
AB  - We demonstrate on-chip generation of correlated pairs of photons in the near
      visible spectrum using a CMOS compatible plasma-enhanced chemical vapor
      deposition silicon nitride photonic device. Photons are generated via spontaneous
      four wave mixing enhanced by a ring resonator with high intrinsic quality Q
      factor of 3,20,000, resulting in a generation rate of 950,000  pairsmW. The high
      brightness of this source offers the opportunity to expand photonic quantum
      technologies over a broad wavelength range and provides a path to develop fully
      integrated quantum chips working at room temperature.

PMID- 29444012
TI  - Engineering spectrally unentangled photon pairs from nonlinear microring
      resonators by pump manipulation.
AB  - The future of integrated quantum photonics relies heavily on the ability to
      engineer refined methods for preparing the quantum states needed to implement
      various quantum protocols. An important example of such states is quantum
      correlated photon pairs, which can be efficiently generated using spontaneous
      nonlinear processes in integrated microring-resonator structures. In this work,
      we propose a method for generating spectrally unentangled photon pairs from a
      standard microring resonator. The method utilizes interference between a primary
      and a delayed secondary pump pulse to effectively increase the pump spectral
      width inside the cavity. This enables on-chip generation of heralded single
      photons with state purities in excess of 99% without spectral filtering.

PMID- 29444013
TI  - Metallic gyroids with broadband circular dichroism.
AB  - Circular dichroism is a useful property for filtering or separating beams
      containing opposite spin angular momentum. Of the many geometries exhibiting
      circular dichroism, the gyroid has proven to be an excellent template for
      exploring circular dichroism in three dimensions. However, the bandwidth of the
      circular dichroism from dielectric gyroids is limited by its narrow circularly
      polarized stop band. Here we investigate conductive silver gyroid micro
      structures using direct laser writing of polymeric templates followed by the
      electroless deposition of a uniform silver coating. We show that the
      transformation from dielectric to silver gyroid micro-structure can increase the
      circular dichroism bandwidth by close to a factor of 3.

PMID- 29444014
TI  - Intensity noise behavior of an InAs/InGaAs quantum dot laser emitting on ground
      states and excited states.
AB  - We experimentally and numerically study the amplitude stability of an InAs/InGaAs
      quantum dot laser emitting simultaneously on ground states (GSs) and excited
      state (ESs) at center wavelengths of 1245 and 1168 nm, respectively. The
      stability is quantified by a spectrally resolved noise current analysis that is
      dependent on the laser injection current. We find a non-monotonic behavior of the
      amplitude noise which shows a reduction of up to 4 dB when the GS and ES emit
      simultaneously. Simulations based on a rate equation model confirm the reduction
      in noise and suggest the cascaded GS and ES carrier paths as the relevant
      underlying mechanism.

PMID- 29444015
TI  - Transmission out-of-plane interferometer to study thermal distributions in
      liquids.
AB  - An optical setup that does not need in-line alignment of the object illumination
      and camera sensor, or requires a reflection mirror after the sample, is
      introduced to observe the optical phase in a heating liquid. This system uses an
      out-of-plane transmission digital holographic interferometer that uniformly adds
      speckle to the image holograms by means of a neutral phase screen. The way in
      which the liquid is illuminated allows having a variable magnification of the
      observed area of the sample. As a proof of principle, a thermal time-dependent
      distribution experiment is presented, whose resulting optical phase readily
      depicts the temperature-time-varying distribution in the liquid.

PMID- 29444016
TI  - Phase-synchronous undersampling in nonlinear spectroscopy.
AB  - We introduce the concept of phase-synchronous undersampling in nonlinear
      spectroscopy. The respective theory is presented and validated experimentally in
      a phase-modulated quantum beat experiment by sampling high phase modulation
      frequencies with low laser repetition rates. The advantage of undersampling in
      terms of signal quality and reduced acquisition time is demonstrated, and
      breakdown conditions are identified. The presented method is particularly
      beneficial for experimental setups with limited signal/detection rates.

PMID- 29444017
TI  - Kerr lens mode-locked Yb:CALGO thin-disk laser.
AB  - We demonstrate the first Kerr lens mode-locked Yb:CaGdAlO4 (Yb:CALGO) thin-disk
      laser oscillator. It generates pulses with a duration of 30 fs at a central
      wavelength of 1048 nm and a repetition rate of 124 MHz. The laser emits the
      shortest pulses generated by a thin-disk laser oscillator, equal to the shortest
      pulse duration obtained by Yb-doped bulk oscillators. The average output power is
      currently limited to 150 mW by the low gain and limited disk quality. We expect
      that more suitable Yb:CALGO disks will enable substantially higher power levels
      with similar pulse durations.

PMID- 29444018
TI  - Recovering a hidden polarization by ghost polarimetry.
AB  - By exploiting polarization correlations of light from a broadband fiber-based
      amplified spontaneous emission source we succeed in reconstructing a hidden
      polarization in a ghost polarimetry experiment in close analogy to ghost imaging
      and ghost spectroscopy. Thereby, an original linear polarization state in the
      object arm of a Mach-Zehnder interferometer configuration which has been
      camouflaged by a subsequent depolarizer is recovered by correlating it with light
      from a reference beam. The variation of a linear polarizer placed inside the
      reference beam results in a Malus law type second-order intensity correlation
      with high contrast, thus measuring a ghost polarigram.

PMID- 29444019
TI  - Group refractive index quantification using a Fourier domain short coherence
      Sagnac interferometer.
AB  - The group refractive index is important in length calibration of Fourier domain
      interferometers by transparent transfer standards. We demonstrate accurate group
      refractive index quantification using a Fourier domain short coherence Sagnac
      interferometer. Because of a justified linear length calibration function, the
      calibration constants cancel out in the evaluation of the group refractive index,
      which is then obtained accurately from two uncalibrated lengths. Measurements of
      two standard thickness coverslips revealed group indices of 1.5426+/-0.0042 and
      1.5434+/-0.0046, with accuracies quoted at the 95% confidence level. This agreed
      with the dispersion data of the coverslip manufacturer and therefore validates
      our method. Our method provides a sample specific and accurate group refractive
      index quantification using the same Fourier domain interferometer that is to be
      calibrated for the length. This reduces significantly the requirements of the
      calibration transfer standard.

PMID- 29444020
TI  - Highly sensitive selectively coated photonic crystal fiber-based plasmonic
      sensor.
AB  - Highly sensitive and miniaturized sensors are highly desirable for real-time
      analyte/sample detection. In this Letter, we propose a highly sensitive plasmonic
      sensing scheme with the miniaturized photonic crystal fiber (PCF) attributes. A
      large cavity is introduced in the first ring of the PCFs for the efficient field
      excitation of the surface plasmon polariton mode and proficient infiltration of
      the sensing elements. Due to the irregular air-hole diameter in the first ring,
      the cavity exhibits the birefringence behavior which enhances the sensing
      performance. The novel plasmonic material gold has been used considering the
      chemical stability in an aqueous environment. The guiding properties and the
      effects of the sensing performance with different parameters have been
      investigated by the finite element method, and the proposed PCFs have been
      fabricated using the stack-and-draw fiber drawing method. The proposed sensor
      performance was investigated based on the wavelength and amplitude sensing
      techniques and shows the maximum sensitivities of 11,000 nm/RIU and 1,420  RIU-1,
      respectively. It also shows the maximum sensor resolutions of 9.1*10-6 and 7*10-6
      RIU for the wavelength and amplitude sensing schemes, respectively, and the
      maximum figure of merits of 407. Furthermore, the proposed sensor is able to
      detect the analyte refractive indices in the range of 1.33-1.42; as a result, it
      will find the possible applications in the medical diagnostics, biomolecules,
      organic chemical, and chemical analyte detection.

PMID- 29444021
TI  - Subwavelength-grating contradirectional couplers for large stopband filters.
AB  - Manipulating the coupling coefficient at subwavelength scales provides an
      additional degree of freedom in designing integrated Bragg gratings. We
      demonstrate asymmetric contradirectional couplers (contra-DCs) using sidewall
      corrugated subwavelength grating (SWG) waveguides for broadband add-drop Bragg
      filters. We show that a SWG can effectively increase the overlap of coupled modes
      and thus the photonic band gap. The measured spectra show good agreement with the
      prediction of photonic band structure simulations. A record bandwidth of 4.07 THz
      (33.4 nm) has been achieved experimentally. A four-port Bragg resonating filter
      made of a phase-shifted Bragg grating SWG contra-DC is also demonstrated for
      narrow-band (near 100 GHz) filtering. All these devices are achieved on the 220
      nm silicon-on-insulator platform with a compact length of less than 150 MUm.
      These large stopband filters may find important applications such as band
      splitting, reconfigurable channel band switching, bandwidth-tunable filtering,
      and dispersion engineering.

PMID- 29444022
TI  - Optical rewritable liquid crystal displays without a front polarizer.
AB  - A front polarizer-free optically rewritable (ORW) liquid crystal display (LCD)
      has been made via a hybrid alignment configuration with dye-doped LCs. The hybrid
      structure consists of one optically active planar and one optically passive
      homeotropic alignment layer. The rewritability of the device is achieved by photo
      reorienting the azo dye molecules in the active planar alignment layer. The dye
      is doped in LCs to function as a polarizer by following the LCs' direction via a
      guest-host effect so that the front polarizer can be eliminated. This makes the
      device more compact and easier to operate for image erasing and rewriting. The
      image rewriting time only requires ~9.0  s, which is determined by the exposure
      energy and LC parameters. The hybrid-mode dye-doped ORW LCD devices could find
      applications in E-paper, transparent display, and various photonics devices.

PMID- 29444023
TI  - Radiation hardness of Ce-doped sol-gel silica fibers for high energy physics
      applications.
AB  - The results of irradiation tests on Ce-doped sol-gel silica using x- and gamma
      rays up to 10 kGy are reported in order to investigate the radiation hardness of
      this material for high-energy physics applications. Sol-gel silica fibers with Ce
      concentrations of 0.0125 and 0.05 mol. % are characterized by means of optical
      absorption and attenuation length measurements before and after irradiation. The
      two different techniques give comparable results, evidencing the formation of a
      main broad radiation-induced absorption band, peaking at about 2.2 eV, related to
      radiation-induced color centers. The results are compared with those obtained on
      bulk silica. This study reveals that an improvement of the radiation hardness of
      Ce-doped silica fibers can be achieved by reducing Ce content inside the fiber
      core, paving the way for further material development.

PMID- 29444024
TI  - Real-time spectral characterization of a photon pair source using a chirped
      supercontinuum seed.
AB  - Photon pair sources have wide ranging applications in a variety of quantum
      photonic experiments and protocols. Many of these protocols require well
      controlled spectral correlations between the two output photons. However, due to
      low cross-sections, measuring the joint spectral properties of photon pair
      sources has historically been a challenging and time-consuming task. Here, we
      present an approach for the real-time measurement of the joint spectral
      properties of a fiber-based four wave mixing source. We seed the four wave mixing
      process using a broadband chirped pulse, studying the stimulated process to
      extract information regarding the spontaneous process. In addition, we compare
      stimulated emission measurements with the spontaneous process to confirm the
      technique's validity. Joint spectral measurements have taken many hours
      historically and several minutes with recent techniques. Here, measurements have
      been demonstrated in 5-30 s depending on resolution, offering substantial
      improvement. Additional benefits of this approach include flexible resolution,
      large measurement bandwidth, and reduced experimental overhead.

PMID- 29444025
TI  - All-dielectric reflective half-wave plate metasurface based on the anisotropic
      excitation of electric and magnetic dipole resonances.
AB  - We present an all-dielectric metasurface that simultaneously supports electric
      and magnetic dipole resonances for orthogonal polarizations. At resonances, the
      metasurface reflects the incident light with nearly perfect efficiency and
      provides a phase difference of pi in the two axes, making a low-loss half-wave
      plate in reflection mode. The polarization handedness of the incident circularly
      polarized light is preserved after reflection; this is different from either a
      pure electric mirror or magnetic mirror. With the features of high reflection and
      circular polarization conservation, the metamirror is an ideal platform for the
      geometric phase-based gradient metasurface functioning in reflection mode.
      Anomalous reflection with the planar meta-mirror is demonstrated as a proof of
      concept. The proposed meta-mirror can be a good alternative to plasmonic
      metasurfaces for future compact and high-efficiency metadevices for polarization
      and phase manipulation in reflection mode.

PMID- 29444026
TI  - 87  fs mode-locked Tm,Ho:CaYAlO4 laser at ~2043  nm.
AB  - We report on, to the best of our knowledge, the first sub-100 fs mode-locked Ho3+
      laser in the 2 MUm spectral range employing a disordered co-doped Tm,Ho:CaYAlO4
      (Tm,Ho:CALYO) crystal as a gain medium. Pulses as short as 87 fs are produced
      with an average output power of 27 mW at 80.45 MHz repetition rate. An output
      power of 96 mW is reached for a pulse duration of 98 fs.

PMID- 29444027
TI  - Controllable photonic crystal with periodic Raman gain in a coherent atomic
      medium.
AB  - With two sets of standing-wave fields built in a thermal rubidium vapor cell, we
      have established a controllable photonic crystal with periodic gain in a
      coherently prepared N-type four-level atomic configuration. First, the photonic
      lattice constructed by a resonant standing-wave coupling field results in a
      spatially modulated susceptibility and makes the signal field diffract in a
      discrete manner under the condition of electromagnetically induced transparency.
      Then, with the addition of the standing-wave pump field, the N-type atomic medium
      can induce a periodic Raman gain on the signal field, which can be effectively
      controlled by tuning the pertinent atomic parameters. The experimental
      demonstration of such a real-time reconfigurable photonic crystal structure with
      periodic Raman gain can pave the way for realizing desired applications predicted
      in the gain-modulated periodic optical systems.

PMID- 29444028
TI  - Doughnut-shaped emission from vertical organic nanowire coupled to thin plasmonic
      film.
AB  - Vertical nanowires facilitate an innovative mechanism to channel the optical
      field in the orthogonal direction and act as a nanoscale light source.
      Subwavelength, vertically oriented nanowire platforms, both of plasmonic and
      semiconducting variety, can facilitate interesting far-field emission profiles
      and potentially carry orbital angular momentum states. Motivated by these
      prospects, in this Letter, we show how a hybrid plasmonic-organic platform can be
      harnessed to engineer far-field radiation. The system that we have employed is an
      organic nanowire made of diaminoanthroquinone grown on a plasmonic gold film. We
      experimentally and numerically studied angular distribution of surface plasmon
      polariton mediated emission from a single, vertical organic nanowire by utilizing
      evanescent excitation and Fourier plane microscopy. Photoluminescence and elastic
      scattering from a single nanowire was analyzed individually in terms of inplane
      momentum states of the outcoupled photons. We found that the emission is doughnut
      shaped in both photoluminescence and elastic scattering regimes. We anticipate
      that the discussed results can be relevant in designing efficient, polariton
      mediated nanoscale photon sources that can carry orbital angular momentum states.

PMID- 29444029
TI  - Polarization- and wavelength-resolved near-field imaging of complex plasmonic
      modes in Archimedean nanospirals.
AB  - Asymmetric nanophotonic structures enable a wide range of opportunities in
      optical nanotechnology because they support efficient optical nonlinearities
      mediated by multiple plasmon resonances over a broad spectral range. The
      Archimedean nanospiral is a canonical example of a chiral plasmonic structure
      because it supports even-order nonlinearities that are not generally accessible
      in locally symmetric geometries. However, the complex spiral response makes
      nanoscale experimental characterization of the plasmonic near-field structure
      highly desirable. Here we employ high-efficiency, high-spatial-resolution
      cathodoluminescence imaging in a scanning transmission electron microscope to
      describe the spatial, spectral, and polarization response of plasmon modes in the
      nanospiral geometry.

PMID- 29444030
TI  - Tomography of asymmetric molecular orbitals with a one-color inhomogeneous field.
AB  - We demonstrate image asymmetric molecular orbitals via high-order harmonic
      generation in a one-color inhomogeneous field. Due to the broken inversion
      symmetry of the inhomogeneous field in space, the returning electrons with energy
      in a broad range can be forced to recollide from only one direction for all the
      orientation angles of molecules, which therefore can be used to reconstruct
      asymmetric molecular orbitals. Following the procedure of molecular orbital
      tomography, the highest occupied molecular orbital of carbon monoxide (CO) is
      satisfactorily reconstructed with high-order harmonic spectra driven by the
      inhomogeneous field. This scheme is helpful to relax the requirement of laser
      conditions and is also applicable to other asymmetric molecules.

PMID- 29444031
TI  - Optical vector network analysis of ultranarrow transitions in 166Er3+ : 7LiYF4
      crystal.
AB  - We present optical vector network analysis (OVNA) of an isotopically purified
      Er1663+:LiYF47 crystal. The OVNA method is based on generation and detection of a
      modulated optical sideband by using a radio-frequency vector network analyzer.
      This technique is widely used in the field of microwave photonics for the
      characterization of optical responses of optical devices such as filters and high
      Q resonators. However, dense solid-state atomic ensembles induce a large phase
      shift on one of the optical sidebands that results in the appearance of extra
      features on the measured transmission response. We present a simple theoretical
      model that accurately describes the observed spectra and helps to reconstruct the
      absorption profile of a solid-state atomic ensemble as well as corresponding
      change of the refractive index in the vicinity of atomic resonances.

PMID- 29444032
TI  - Two-dimensional electronic-Raman spectroscopy.
AB  - We present a new technique, two-dimensional electronic-Raman spectroscopy (2DER),
      which combines femtosecond stimulated Raman spectroscopy and a pulse-shaper
      assisted 2D spectroscopic scheme for the actinic pump. The 2DER spectrum presents
      the initial actinic excitation wavelength with nanometer spectral resolution in
      the first axis and the detected stimulated Raman spectra in the second axis. We
      measured the correlation of the electronic and vibrational states in the
      photosynthetic accessory pigment beta-carotene and reveal its photoexcited state
      manifold.

PMID- 29444033
TI  - Watt-level widely tunable femtosecond mid-infrared KTiOAsO4 optical parametric
      oscillator pumped by a 1.03  MUm Yb:KGW laser.
AB  - A high-power, high-repetition-rate, broadband tunable femtosecond optical
      parametric oscillator (OPO) is constructed based on KTiOAsO4 crystal, pumped by a
      75.5 MHz mode-locked Yb:KGW laser. With 7 W pump power, the OPO generates as much
      as 2.32 W of signal power at 1.55 MUm and 1.31 W of idler power at 3.05 MUm,
      corresponding to a total conversion efficiency of 51.8%. Operating at 151 MHz
      repetition rate, the wavelength of the signal covers 1.41-1.71 MUm with a tunable
      idler range of 2.61-3.84 MUm. The idler bandwidth is more than 180 nm over the
      entire mid-infrared range. By compensating intracavity dispersion, the signal
      pulse has a nearly Fourier transform-limited duration of 129 fs at 1.52 MUm.

PMID- 29444034
TI  - Label-free cell nuclear imaging by Gruneisen relaxation photoacoustic microscopy.
AB  - Photoacoustic microscopy (PAM) with ultraviolet (UV) laser illumination has
      recently been demonstrated as a promising tool that provides fast, label-free,
      and multilayered histologic imaging of human breast tissue. Thus far, the axial
      resolution has been determined ultrasonically. To enable optically defined axial
      resolution, we exploit the Gruneisen relaxation (GR) effect. By imaging mouse
      brain slices, we show that GRUV-PAM reveals detailed information about three
      dimensional cell nuclear distributions and internal structures, which are
      important diagnostic features for cancers. Due to the nonlinear effect, GRUV-PAM
      also provides better contrast in images of cell nuclei.

PMID- 29444035
TI  - Power scalable 10  W 976  nm single-frequency linearly polarized laser source.
AB  - A 10 W level 976 nm single-frequency linearly polarized laser source was
      demonstrated with a two-stage all-fiber amplifier configuration. The continuous
      wave output power of 10.1 W was obtained from the second stage amplifier by using
      a 20/130 MUm single-mode, polarization maintaining, 1.5 wt. % ytterbium-doped
      phosphate double-clad fiber. This all-fiber single-frequency laser source is very
      promising for watt-level deep ultraviolet laser generation via frequency
      quadrupling.

PMID- 29444036
TI  - Pulse carving using nanocavity-enhanced nonlinear effects in photonic crystal
      Fano structures.
AB  - We experimentally demonstrate the use of a photonic crystal Fano resonance for
      carving-out short pulses from long-duration input pulses. This is achieved by
      exploiting an asymmetric Fano resonance combined with carrier-induced nonlinear
      effects in a photonic crystal membrane structure. The use of a nanocavity
      concentrates the input field to a very small volume leading to an efficient
      nonlinear resonance shift that carves a short pulse out of the input pulse. Here,
      we demonstrate shortening of ~500  ps and ~100  ps long pulses to ~30  ps and ~20
      ps pulses, respectively. Furthermore, we demonstrate error-free low duty cycle
      return-to-zero signal generation at 2 Gbit/s with energy consumption down to ~1 
      pJ/bit and power penalty of ~2  dB. The device physics and limitations are
      analyzed using nonlinear coupled-mode theory.

PMID- 29444037
TI  - Surface plasmon microscopy by spatial light switching for label-free imaging with
      enhanced resolution.
AB  - In this Letter, we describe spatially switched surface plasmon microscopy (ssSPM)
      based on two-channel momentum sampling. The performance evaluated with periodic
      nanowires in comparison with conventional SPM and bright-field microscopy shows
      that the resolution of ssSPM is enhanced by almost 15 times over conventional
      SPM. ssSPM provides an extremely simple way to attain diffraction limit in SPM
      and to go beyond for super-resolution in label-free microscopy techniques.

PMID- 29444038
TI  - Phosphor-in-glass with Nd-doped glass for a white LED with a wide color gamut.
AB  - A phosphor-in-glass (PiG) with red and green phosphors using Nd-doped glass as a
      host matrix was fabricated to produce a white light emitting diode (wLED) with a
      wide color gamut. The Lu3Al5O12:Ce3+ and CaAlSiN3:Eu2+ contents were adjusted to
      achieve white emission for liquid crystal display (LCD) applications. The
      silicate glass was doped with varying concentrations of Nd2O3 to modify the
      photoluminescence spectra of the wLED, by the hypersensitive absorption of the
      Nd3+:I9/24->G5/24,G27/2 transition. The color coordination, the color rendering
      index, and the color co-related temperature of the PiG-mounted LEDs were modified
      by the introduction of Nd3+. The color gamut of the wLED was monitored and found
      to have effectively improved with the Nd3+-doped silicate glass.

PMID- 29444039
TI  - Programmable quantum random number generator without postprocessing.
AB  - We demonstrate a viable source of unbiased quantum random numbers whose
      statistical properties can be arbitrarily programmed without the need for any
      postprocessing such as randomness distillation or distribution transformation. It
      is based on measuring the arrival time of single photons in shaped temporal modes
      that are tailored with an electro-optical modulator. We show that quantum random
      numbers can be created directly in customized probability distributions and pass
      all randomness tests of the NIST and Dieharder test suites without any randomness
      extraction. The min-entropies of such generated random numbers are measured close
      to the theoretical limits, indicating their near-ideal statistics and ultrahigh
      purity. Easy to implement and arbitrarily programmable, this technique can find
      versatile uses in a multitude of data analysis areas.

PMID- 29444040
TI  - Self-assembled monolayers of bimetallic Au/Ag nanospheres with superior surface
      enhanced Raman scattering activity for ultra-sensitive triphenylmethane dyes
      detection.
AB  - The bimetallic Au/Ag self-assembled monolayers (SAMs) were constructed by using
      mono-dispersed Au/Ag nanospheres (Ag: 4.07%-34.53%) via evaporation-based
      assembly strategy. The composition-dependent surface-enhanced Raman scattering
      (SERS) spectroscopy revealed that the Au/Ag (Ag: 16.83%) SAMs provide maximized
      activity for triphenylmethane dyes detection. With the inter-metallic synergy,
      the optimized SAMs enable the Raman intensity of crystal violet molecules to be
      about 223 times higher than that of monometallic Au SAMs. Moreover, the SERS
      signals with excellent uniformity (<5% variation) are sensitive down to 10-13  M
      concentrations because of the optimal matching between bimetallic plasmon
      resonance and the incident laser wavelength.

PMID- 29444041
TI  - Refractive index sensor based on graphene-coated photonic surface-wave resonance.
AB  - We propose a graphene-coated photonic system with the excitation of Bloch surface
      waves (BSWs) for refractive index sensing. Through manipulation of the BSW
      resonance in the truncated photonic crystal under a Kretschmann configuration,
      the absorption in a graphene monolayer is significantly enhanced, assisted by the
      strong electromagnetic confinement of BSWs. The sharp and low reflectivity dip
      and the strong wave-environment interaction enable highly sensitive optical
      sensing. First-order perturbation theory and transfer-matrix calculation indicate
      that the system sensitivity is strongly related to the ratio of the electric
      field energy in the detection area, operation wavelength, and incident angle.
      Study shows that the wavelength sensitivity and figure of merit of the optimized
      system can reach 7023  nm/RIU and 196.44, respectively. More generalized BSW
      system configurations, e.g., aperiodic BSW design, are proposed for refractive
      index sensing application.

PMID- 29444042
TI  - Atom-resonant squeezed light from a tunable monolithic ppRKTP parametric
      amplifier.
AB  - We demonstrate vacuum squeezing at the D1 line of atomic rubidium (795 nm) with a
      tunable, doubly-resonant, monolithic subthreshold optical parametric oscillator
      in periodically-poled Rb-doped potassium titanyl phosphate (ppRKTP). The
      squeezing appears to be undiminished by a strong dispersive optical nonlinearity
      recently observed in this material.

PMID- 29444043
TI  - Single-mode ultraviolet whispering gallery mode lasing from a floating GaN
      microdisk.
AB  - We fabricated a floating GaN microdisk supported by a silicon pillar through
      photolithography, dry-etching GaN, and isotropic wet-etching silicon methods.
      Single-mode ultraviolet whispering gallery mode (WGM) lasing was obtained from
      the floating GaN microdisk under optical pumping conditions at room temperature.
      The features of WGM lasing, i.e., the threshold, emission intensity, and lasing
      mode number, were characterized. A two-dimensional finite-difference time-domain
      simulation about the optical field contour profile also confirmed the resonance
      mechanism of WGM lasing. This work can help realize single-mode WGM lasing with
      high quality factor and low threshold.

PMID- 29444044
TI  - Intensity statistics in a long random fiber Raman laser.
AB  - We study the output emission statistics of a random continuous-wave Raman fiber
      laser. The signal evolution is governed by a generalized nonlinear Schrodinger
      equation (NLSE) with inserted gain. The statistics are close to the Rayleigh one,
      and the deviations are caused by the Kerr nonlinearity. To characterize the
      deviations, we analytically find the mean of the squared output signal intensity,
      based on the kinetic theory. We show qualitative agreement with available
      experimental data and supplement the results with numerical calculations. With
      the limit of small gain, the kinetic theory gives a finite answer for the mean of
      squared intensity in the first and the second order with respect to small
      nonlinearity. The result is consistent with the fact that the NLSE is integrable
      in the case of zero gain and is applicable to any generalized NLSE if the
      inserted terms are effectively small.

PMID- 29444045
TI  - Few-period helically twisted all-solid photonic bandgap fibers.
AB  - We present a type of few-period helically twisted all-solid photonic bandgap
      fiber (AS-PBGFs). The helical structure leads to orbital resonance of a cladding
      rod light, which couples with the core mode. A two-period twist structure
      exhibits an extremely strong resonant dip of up to 30 dB. A series of samples
      with twist periods of 3.31-7.92 mm (yielding twist rates of 1.90-0.79  rad?mm-1)
      in association with different resonance orders are fabricated and demonstrated.
      The inherent physical mechanism underlying the resonance is analyzed. Moreover,
      the responses of the resonance to mechanical torsion, strain, and temperature are
      investigated. The twisted AS-PBGFs feature high reproducibility, stability, and
      robustness, and have great potential in tunable in-fiber filters and sensors.

PMID- 29444046
TI  - On-chip optical transduction scheme for graphene nano-electro-mechanical systems
      in silicon-photonic platform.
AB  - We present a scheme for on-chip optical transduction of strain and displacement
      of graphene-based nano-electro-mechanical systems (NEMS). A detailed numerical
      study on the feasibility of three silicon-photonic integrated circuit
      configurations is presented: the Mach-Zehnder interferometer (MZI), the micro
      ring resonator, and the ring-loaded MZI. An index sensing based technique using
      an MZI loaded with a ring resonator with a moderate Q-factor of 2400 can yield a
      sensitivity of 28  fm/Hz and 6.5*10-6%/Hz for displacement and strain,
      respectively. Though any phase-sensitive integrated-photonic device could be used
      for optical transduction, here we show that optimal sensitivity is achievable by
      combining resonance with phase sensitivity.

PMID- 29444047
TI  - Homographically generated light sheets for the microscopy of large specimens.
AB  - We compare the performance of linear and nonlinear methods for aligning the
      excitation and detection planes throughout volumes of large specimens in
      digitally scanned light sheet microscopy. An effective nonlinear method involves
      the registration of four corner extrema of the imaging volume via a projective
      transform. We show that this improves the light collection efficiency of the
      commonly used three-point affine registration by an average of 42% over a typical
      specimen volume. Accurate illumination/detection registration methods are now
      pertinent to biological research in view of current trends towards imaging large
      or expanded samples, at depth, with diffraction limited resolution.

PMID- 29444048
TI  - Intense broadband mid-infrared pulses of 280  MV/cm for supercontinuum generation
      in gaseous medium.
AB  - We produce extremely bright mid-infrared (mid-IR) pulses with a tunable
      wavelength of 7 MUm to 15 MUm through difference frequency generation.
      Optimization of beam quality and beam focusing results in an intense mid-IR field
      spatiotemporally confined in the lambda-cubic volume. A near planar wavefront is
      achieved through manipulating the wavefront curvature of the pumping pulse in the
      frequency downconversion process. Coherent mid-IR pulses are produced with the
      peak field of 280 MV/cm at 10 MUm, and its intensity exceeds 100  TW/cm2,
      estimated from measured pulse energy, and spatial and temporal pulse profiles.
      Interaction of such an intense mid-IR field with Xe and Kr gas forms plasma and
      generates a supercontinuum in the visible range.

PMID- 29444049
TI  - Large-area rainbow holographic diffraction gratings on a curved surface using
      transferred photopolymer films.
AB  - We report the fabrication of large-area holographic diffraction gratings on a
      curved surface from transferred photopolymer films by introducing a water-soluble
      interlayer. The holographic gratings on a curved surface have a diffraction
      efficiency of ~63%, which is ~80% of the recorded holographic film on a flat
      surface. By transferring a recorded holographic grating to a flat substrate, we
      obtained rainbow holographic gratings under white light illumination. This can be
      explained by the deformation of the holographic gratings. Our result provides a
      low-cost method for fabricating diffraction optical elements on a curved surface
      for optical systems.

PMID- 29444050
TI  - Bioresorbable optical fiber Bragg gratings.
AB  - We demonstrate, for the first time, an inscription and wet dissolution study of
      Bragg gratings in a bioresorbable calcium-phosphate glass optical fiber. Bragg
      gratings, with average refractive index changes of 5.8*10-4, were inscribed using
      193 nm excimer laser radiation. Results on the dissolution of the irradiated
      fiber in simulated physiological conditions are presented after immersing a
      tilted Bragg grating in a phosphate buffered saline solution for 56 h; selective
      chemical etching effects are also reported. The investigations performed pave the
      way toward the use of such phosphate glass fiber Bragg gratings for the
      development of soluble photonic sensing probes for the efficient in vivo
      monitoring of vital mechanical or chemical parameters.

PMID- 29444051
TI  - Ultrasensitive measurement of gas refractive index using an optical nanofiber
      coupler.
AB  - We report an ultrasensitive gas refractive index (RI) sensor based on optical
      nanofiber couplers (ONCs). Theoretical analysis reveals that a dispersion turning
      point (DTP) exists when the diameter of the coupler is below 1000 nm. Leveraging
      this DTP, the gas RI sensitivity can be significantly improved to infinity. Then
      we experimentally demonstrate a DTP and achieve ultrahigh sensitivities of 46,470
      nm/refractive index unit (RIU) and -45,550  nm/RIU around the DTP using an ONC
      with a diameter of 700 nm. More importantly, the unique twin dips/peaks
      interference characteristics around the DTP offers further enhancement on the
      sensitivity to 92,020  nm/RIU. The demonstrated sensor not only shows vast
      potential in ultrasensitive pressure sensing, acoustic sensing, gas sensing, and
      gas phase biomarker detection, but also provides a new tool for nonlinear optics,
      ultrafast optics, quantum optics, and ultracold atom optics.

PMID- 29444052
TI  - Multiple scattering of light in discrete random media using incoherent
      interactions.
AB  - We consider the scattering and absorption of light in discrete random media of
      densely packed spherical particles. In what we term "radiative transfer with
      reciprocal transactions" (R2T2), we introduce a volume element of the random
      medium, derive its scattering and absorption characteristics using the
      superposition T-Matrix method (STMM), and compute its frequency-domain incoherent
      volume-element scattering characteristics. Using an order-of-scattering approach,
      we then compute a numerical Monte Carlo solution for the scattering problem with
      an exact treatment of the interaction between two volume elements. We compute
      both the direct and reciprocal contributions along a sequence of volume elements,
      allowing us to evaluate the coherent backscattering effects. We show that the
      R2T2 and exact STMM solutions are in mutual agreement for large finite systems of
      densely packed spherical particles. We conclude that the R2T2 method provides a
      viable numerical solution for scattering by asymptotically infinite systems of
      particles.

PMID- 29444053
TI  - Terahertz nonreciprocal isolator based on a magneto-optical microstructure at
      room temperature.
AB  - We investigated THz nonreciprocal circularly polarized transmission in thin
      longitudinally magnetized InSb film, especially focusing on its non-eigen
      nonreciprocal transmission mechanism at room temperature. Then, based on this
      effect, we presented a THz isolator for linear polarized waves. The nonreciprocal
      transmission of the InSb film in this device is converted and enhanced by a pair
      of orthogonal artificial birefringence gratings. After the optimization, the
      isolation reaches 24 dB, and the insertion loss is <0.5  dB at room temperature
      and a low magnetic field.

PMID- 29444054
TI  - 3D thickness map reconstruction of dielectric thin films using scattering of
      surface plasmon polaritons.
AB  - Thin films are key elements in the current development of nanotechnology, and
      their characterization has become an essential task. In this Letter, we report on
      a technique to reconstruct full 3D maps of dielectric thin films using the
      scattered light of decoupled surface plasmon polaritons. Patterned magnesium
      fluoride thin films were fabricated, and their 3D thickness map was fully
      reconstructed with high (<1  nm) precision. This technique can be applied and
      easily adjusted to identify inhomogeneities in wide areas (mm2-cm2) of dielectric
      samples with subnanometer precision, or to characterize the fabrication processes
      involved in the preparation of patterned multilayered systems.

PMID- 29444055
TI  - Dynamically stable Nd:YAG resonators with beam quality beyond the birefringence
      limit and pumping of a singly resonant optical parametric oscillator.
AB  - A simple, reliable, linearly polarized laser source with very high beam quality
      is demonstrated using standard diode-side-pumped Nd:YAG modules. The laser
      produced 30 W of output power with beam quality factor M2<1.15 over the entire
      range of input powers and beam quality of 1.02 at the laser operation point. This
      is, to our knowledge, the highest beam quality for a dynamically stable high
      power laser that uses an optically isotropic crystal. The laser was used as a
      pump source for an optical parametric oscillator based on a periodically poled
      lithium niobate, producing wavelength in the 1.5-3.8 MUm range.

PMID- 29444056
TI  - High-resolution multiphoton microscopy with a low-power continuous wave laser
      pump.
AB  - Multiphoton microscopy (MPM) has been widely used for three-dimensional
      biological imaging. Here, based on the photon-induced charge state conversion
      process, we demonstrated a low-power high-resolution MPM with a nitrogen vacancy
      (NV) center in diamond. Continuous wave green and orange lasers were used to pump
      and detect the two-photon charge state conversion, respectively. The power of the
      laser for multiphoton excitation was 40 MUW. Both the axial and lateral
      resolutions were improved approximately 1.5 times compared with confocal
      microscopy. The results can be used to improve the resolution of the NV center
      based quantum sensing and biological imaging.

PMID- 29444057
TI  - Measurement of the surface susceptibility and the surface conductivity of
      atomically thin MoS2 by spectroscopic ellipsometry.
AB  - We show how to correctly extract from the ellipsometric data the surface
      susceptibility and the surface conductivity that describe the optical properties
      of monolayer MoS2. Theoretically, these parameters stem from modelling a single
      layer two-dimensional crystal as a surface current, a truly two-dimensional
      model. Current experimental practice is to consider this model equivalent to a
      homogeneous slab with an effective thickness given by the interlayer spacing of
      the exfoliating bulk material. We prove that the error in the evaluation of the
      surface susceptibility of monolayer MoS2, owing to the use of the slab model, is
      at least 10% or greater, a significant discrepancy in the determination of the
      optical properties of this material.

PMID- 29444058
TI  - High-order super-resolution optical fluctuation imaging based on low-pass
      denoising.
AB  - A new scheme of super-resolution optical fluctuation imaging (SOFI) is proposed
      to broaden its application in the high-order case by separating the elimination
      of shot noise from the computation of cumulant, applying the low-pass denoising
      (LPD) operator to SOFI. The high-order cumulants are derived from a basic
      recursion of moments with the suppression of shot noise by the LPD on raw data.
      SOFI based on LPD (LPD-SOFI) demonstrates a 10.6-fold lateral resolution
      enhancement with the cumulant order of the 16th and a seven-fold three
      dimensional resolution enhancement with the cumulant order of the 10th in
      experiments performed on a sparse sample of quantum dots.

PMID- 29444059
TI  - 250  W clad pumped Raman all-fiber laser with brightness enhancement.
AB  - We report a strictly all-fiber clad pumped Raman fiber laser with a CW power of
      250 W. To the best of our knowledge, this is the highest power Raman fiber laser
      demonstrated in any configuration allowing brightness enhancement. In addition,
      this is the first report of a Raman clad pumped all-fiber laser. The brightness
      of the pump source was enhanced by a factor of ~3.8. This result was achieved by
      the design of a novel triple-clad fiber, with tight pump power inner confining
      clad that both maximized the Raman gain and inhibited the second Stokes
      radiation. We discuss power-increase effects on the beam quality, efficiency, and
      brightness enhancement.

PMID- 29444060
TI  - Shot-noise-limited Doppler-broadened noise-immune cavity-enhanced optical
      heterodyne molecular spectrometry.
AB  - Shot-noise-limited Doppler-broadened (Db) noise-immune cavity-enhanced optical
      heterodyne molecular spectrometry (NICE-OHMS) has been realized by implementation
      of balanced detection. A characterization of the system based on Allan-Werle
      plots of the absorption coefficient, retrieved by fitting a model function to
      data, shows that the system has a white noise equivalent absorption per unit
      length per square root of bandwidth of 2.3*10-13  cm-1 Hz-1/2, solely 44% above
      the shot noise limit, and a detection sensitivity of 2.2*10-14  cm-1 over 200 s,
      both being unprecedented for Db NICE-OHMS. The white noise response follows the
      expected inverse square root dependence on power that is representative of a shot
      noise-limited response, which confirms that the system is shot-noise-limited.

PMID- 29444061
TI  - High-performance on-chip autocorrelator using a rib waveguide loaded with two
      photon absorption diodes.
AB  - We report an on-chip autocorrelator comprising a Si rib waveguide and two-photon
      absorption photodiodes in which two pulses simultaneously propagate in opposite
      directions, and their correlation is acquired. The rib waveguide's broadband
      guiding mode and moderately low group index allow the device to operate over a
      wide wavelength range with high resolution. We confirm that the waveguide has a
      transmission band of at least 1300-1630 nm and observed correlation waveforms for
      pulses of the order of several hundred femtoseconds to several picoseconds, with
      a range of at least the entire C band region.

PMID- 29444062
TI  - 40  Gb/s indoor optical wireless system enabled by a cyclically arranged optical
      beamsteering receiver.
AB  - Indoor optical wireless communication with optical beamsteering capability is
      currently attracting a lot of attention. One major two-dimensional (2D) optical
      beamsteering scheme is realized by 2D grating or its active counterpart, which is
      usually based on a spatial light modulator (SLM). However, there is a fundamental
      trade-off between the field of view (FoV) and power efficiency due to the
      inherent feature of gratings. In this Letter, we propose a new class of 2D
      beamsteering, named cyclically arranged optical beamsteering (CAO-BS), which can
      break that trade-off. Traditional 2D gratings extend the optical beam in the
      Cartesian coordinates (1D grating in horizontal + 1D grating in vertical), while
      CAO-BS extends the optical beam in the polar coordinates (1D grating + angular
      rotation). Since only 1D grating is engaged, the power efficiency increases with
      the number of grating lobes reduced. In the polar coordinates, the angle rotation
      tuning in a SLM is quasi-continuous in a full 2pi range. The CAO-BS is
      demonstrated at the receiving end in an indoor experimental system. The FoV is 18
      degrees  by 360 degrees  in polar coordinates without any additional mechanical
      parts. Based on the CAO-BS, 40 Gbit/s on-off keying data is also successfully
      transmitted over 1 km single-mode fiber and 0.5 m free space.

PMID- 29444063
TI  - Ultrahigh-resolution and wideband optical vector analysis for arbitrary
      responses.
AB  - An ultrahigh-resolution and wideband optical vector analyzer (OVA) with the
      simplest architecture, to the best of our knowledge, is proposed and demonstrated
      based on chirped optical double-sideband (ODSB) modulation in a single-drive Mach
      Zehnder modulator (MZM). To distinguish the magnitude and phase information
      carried by the two sidebands in the ODSB signal, a two-step measurement, in which
      biasing, respectively, the MZM at two different points is applied. Because no
      optical filtering is required in the scheme, the optical carrier can be located
      at any wavelength that is suitable for accurate measurement, e.g., close to the
      notch of a notch response or within the passband of a bandpass response, so the
      proposed OVA has the capability to measure an arbitrary response. An experiment
      is carried out, which achieves the magnitude and phase responses of a
      programmable optical processor with bandpass, notch, or falling-edge responses.
      The measurement bandwidth is 134 GHz, and the measurement resolution is 1.12 MHz.

PMID- 29444064
TI  - Optimized random phase only holograms.
AB  - We propose a simple and efficient technique capable of generating Fourier phase
      only holograms with a reconstruction quality similar to the results obtained with
      the Gerchberg-Saxton (G-S) algorithm. Our proposal is to use the traditional G-S
      algorithm to optimize a random phase pattern for the resolution, pixel size, and
      target size of the general optical system without any specific amplitude data.
      This produces an optimized random phase (ORAP), which is used for fast generation
      of phase only holograms of arbitrary amplitude targets. This ORAP needs to be
      generated only once for a given optical system, avoiding the need for costly
      iterative algorithms for each new target. We show numerical and experimental
      results confirming the validity of the proposal.

PMID- 29444065
TI  - Compact burst-mode Nd:YAG laser for kHz-MHz bandwidth velocity and species
      measurements.
AB  - A compact-footprint (0.18  m2) flash-lamp-pumped, burst-mode Nd:YAG-based master
      oscillator pulsed-amplifier laser is reported with a fundamental 1064 nm output
      of over 14 J per burst. A directly modulated diode laser seed source is used to
      generate 10 ms duration arbitrary sequences of 500 kHz doublet or MHz singlet
      pulses for flow-field velocity or species measurements, respectively. Flexible
      pulse widths are used to balance the energy distribution of pulse doublets and
      achieve second-harmonic conversion efficiencies up to 42%. Burst-mode laser
      performance characteristics, measurement accuracies in turbulent flows, and
      prospects for kHz-MHz flow-field diagnostics are discussed.

PMID- 29444066
TI  - Dual-wavelength digital holographic phase and fluorescence microscopy for an
      optical thickness encoded suspension array.
AB  - A dual-wavelength digital holographic phase and fluorescence microscopy system is
      demonstrated as the decoding and detection platform of an optical thickness
      encoded suspension array. The phase imaging path is designed to decode optical
      thickness encoded microcarriers, and the fluorescence imaging path is used to
      detect the quantitative information of the bound target analytes. The encoding
      capacity could be more than 100. The decoding reliability of the phase imaging
      path is verified by a multiplexed immunoassay experiment. The ability for
      quantitative analysis of the fluorescence imaging path is confirmed by
      concentration gradient experiments. This method offers high decoding accuracy and
      high detection sensitivity of label signals.

PMID- 29444067
TI  - Arbitrary shaping of biphoton correlations using near-field frequency-to-time
      mapping.
AB  - Frequency-to-time mapping (FTM) is a technique used to mirror the spectral shape
      of an optical waveform in the time domain. The regular approach, based on the far
      field condition, requires large amounts of dispersion for successful mapping.
      However, when the far-field condition is insurmountable for achieving a desired
      temporal profile, another technique, termed near-field FTM, can be employed to
      assist with the mapping. For the first time, we demonstrate a shaper-assisted
      near-field FTM using entangled photon pairs. By pre-modifying the two-photon
      spectral amplitude and phase before propagating the photon pairs through
      dispersion, we can achieve arbitrary temporal correlations in the near-field
      region.

PMID- 29444068
TI  - Multi-distance diffuse optical spectroscopy with a single optode via
      hypotrochoidal scanning.
AB  - Frequency-domain diffuse optical spectroscopy (FD-DOS) is an established
      technique capable of determining optical properties and chromophore
      concentrations in biological tissue. Most FD-DOS systems use either manually
      positioned, handheld probes or complex arrays of source and detector fibers to
      acquire data from many tissue locations, allowing for the generation of 2D or 3D
      maps of tissue. Here, we present a new method to rapidly acquire a wide range of
      source-detector (SD) separations by mechanically scanning a single SD pair. The
      source and detector fibers are mounted on a scan head that traces a
      hypotrochoidal pattern over the sample that, when coupled with a high-speed FD
      DOS system, enables the rapid collection of dozens of SD separations for depth
      resolved imaging. We demonstrate that this system has an average error of 4+/
      2.6% in absorption and 2+/-1.8% in scattering across all SD separations.
      Additionally, by linearly translating the device, the size and location of an
      absorbing inhomogeneity can be determined through the generation of B-scan images
      in a manner conceptually analogous to ultrasound imaging. This work demonstrates
      the potential of single optode diffuse optical scanning for depth resolved
      visualization of heterogeneous biological tissues at near real-time rates.

PMID- 29444069
TI  - Optical spectral sweep comb liquid flow rate sensor.
AB  - In microfluidic chip applications, the flow rate plays an important role. Here we
      propose a simple liquid flow rate sensor by using a tilted fiber Bragg grating
      (TFBG) as the sensing element. As the water flows in the vicinity of the TFBG
      along the fiber axis direction, the TFBG's spectrum changes due to its contact
      with water. By comparing the time-swept spectra of the TFBG in water to that of
      the TFBG with water flowing over it, a spectral sweep comb was formed, and the
      flow rate can be detected by selecting a suitable sweeping frequency. The
      proposed sensor has a high Q-value of over 17,000 for the lower rate and a large
      detectable range from 0.0058 mm/s to 3.2 mm/s. And the calculated corresponding
      lower detectable flow rate of 0.03 nL/s is 3 orders magnitude better than that of
      the current fiber flowmeter. Meanwhile, the proposed sensor has the temperature
      self-compensation function for the variation of the external temperature. We
      believe that this simple configuration will open a research direction of the TFBG
      deriving theory and configuration for lower flow rate measurements for
      microfluidic chip applications.

PMID- 29444070
TI  - High efficiency all-fiber cylindrical vector beam laser using a long-period fiber
      grating.
AB  - We demonstrate a novel all-fiber laser generating cylindrical vector beams with
      high slope efficiency and low threshold by introducing a long-period fiber
      grating into the laser cavity. Highly efficient mode conversion is realized by an
      LPFG at ~1548  nm. Mode selection and spectrum filtering are achieved in
      combination with a two-mode fiber Bragg grating (TM-FBG). The fiber laser
      operates at a single wavelength of 1547.95 nm with a 30 dB linewidth of less than
      0.18 nm and a side-mode suppression ratio (SMSR) of more than 56 dB. The lasing
      threshold and slope efficiency of the laser are 24.5 mW and 35.41%, respectively.
      The output power is 72 mW with an absorbed pump power of 225 mW. The variation of
      slope efficiency with respect to the reflectivity of the TM-FBG is investigated.
      Through adjusting the intra-cavity polarization controller, high-purity radially
      and azimuthally polarized beams are both obtained.

PMID- 29444072
TI  - Fruit flies are multistable geniuses.
AB  - Our sensory systems have evolved to provide us with information about the
      external world. Such information is useful only insofar as it leads to actions
      that enhance fitness, and thus, the link between sensation and action has been
      thoroughly studied in many species. In insects, for example, specific visual
      stimuli lead to highly stereotyped responses. In contrast, humans can exhibit a
      wide range of responses to the same stimulus, as occurs most notably in the
      phenomenon of multistable perception. On this basis, one might think that humans
      have a fundamentally different way of generating actions from sensory inputs, but
      Toepfer et al. show that flies show evidence of multistable perception as well.
      Specifically, when confronted with a sensory stimulus that can yield different
      motor responses, flies switch from one response to another with temporal dynamics
      that are similar to those of humans and other animals. This suggests that the
      mechanisms that give rise to the rich repertoire of sensory experience in humans
      have correlates in much simpler nervous systems.

PMID- 29444071
TI  - The PHD finger protein Spp1 has distinct functions in the Set1 and the meiotic
      DSB formation complexes.
AB  - Histone H3K4 methylation is a feature of meiotic recombination hotspots shared by
      many organisms including plants and mammals. Meiotic recombination is initiated
      by programmed double-strand break (DSB) formation that in budding yeast takes
      place in gene promoters and is promoted by histone H3K4 di/trimethylation. This
      histone modification is recognized by Spp1, a PHD finger containing protein that
      belongs to the conserved histone H3K4 methyltransferase Set1 complex. During
      meiosis, Spp1 binds H3K4me3 and interacts with a DSB protein, Mer2, to promote
      DSB formation close to gene promoters. How Set1 complex- and Mer2- related
      functions of Spp1 are connected is not clear. Here, combining genome-wide
      localization analyses, biochemical approaches and the use of separation of
      function mutants, we show that Spp1 is present within two distinct complexes in
      meiotic cells, the Set1 and the Mer2 complexes. Disrupting the Spp1-Set1
      interaction mildly decreases H3K4me3 levels and does not affect meiotic
      recombination initiation. Conversely, the Spp1-Mer2 interaction is required for
      normal meiotic recombination initiation, but dispensable for Set1 complex
      mediated histone H3K4 methylation. Finally, we provide evidence that Spp1
      preserves normal H3K4me3 levels independently of the Set1 complex. We propose a
      model where Spp1 works in three ways to promote recombination initiation: first
      by depositing histone H3K4 methylation (Set1 complex), next by "reading" and
      protecting histone H3K4 methylation, and finally by making the link with the
      chromosome axis (Mer2-Spp1 complex). This work deciphers the precise roles of
      Spp1 in meiotic recombination and opens perspectives to study its functions in
      other organisms where H3K4me3 is also present at recombination hotspots.

PMID- 29444073
TI  - Projected future impact of HPV vaccination and primary HPV screening on cervical
      cancer rates from 2017-2035: Example from Australia.
AB  - BACKGROUND: Many countries are transitioning from cytology-based to longer
      interval HPV screening. Trials comparing HPV-based screening to cytology report
      an increase in CIN2/3 detection at the first screen, and longer-term reductions
      in CIN3+; however, population level year-to-year transitional impacts are poorly
      understood. We undertook a comprehensive evaluation of switching to longer
      interval primary HPV screening in the context of HPV vaccination. We used
      Australia as an example setting, since Australia will make this transition in
      December 2017. METHODS: Using a model of HPV vaccination, transmission, natural
      history and cervical screening, Policy1-Cervix, we simulated the planned
      transition from recommending cytology every two years for sexually-active women
      aged 18-20 to 69, to recommending HPV screening every five years for women aged
      25-74 years. We estimated rates of CIN2/3, cervical cancer incidence, and
      mortality for each year from 2005 to 2035, considering ranges for HPV test
      accuracy and screening compliance in the context of HPV vaccination (current
      coverage ~82% in females; ~76% in males). FINDINGS: Transient increases are
      predicted to occur in rates of CIN2/3 detection and invasive cervical cancer in
      the first two to three years following the screening transition (of 16-24% and 11
      14% in respectively, compared to 2017 rates). However, by 2035, CIN2/3 and
      invasive cervical cancer rates are predicted to fall by 40-44% and 42-51%,
      respectively, compared to 2017 rates. Cervical cancer mortality rates are
      predicted to remain unchanged until ~2020, then decline by 34-45% by 2035. Over
      the period 2018-2035, switching to primary HPV screening in Australia is expected
      to avert 2,006 cases of invasive cervical cancer and save 587 lives. CONCLUSIONS:
      Transient increases in detected CIN2/3 and invasive cancer, which may be
      detectable at the population level, are predicted following a change to primary
      HPV screening. This is due to improved test sensitivity bringing forward
      diagnoses, resulting in longer term reductions in both cervical cancer incidence
      and mortality. Fluctuations in health outcomes due to the transition to a longer
      screening interval are predicted to occur for 10-15 years, but cervical cancer
      rates will be significantly reduced thereafter due to the impact of HPV
      vaccination and HPV screening. In order to maintain confidence in primary HPV
      screening through the transitional phase, it is important to widely communicate
      that an initial increase in CIN2/3 and perhaps even invasive cervical cancer is
      expected after a national transition to primary HPV screening, that this
      phenomenon is due to increased prevalent disease detection, and that this effect
      represents a marker of screening success.

PMID- 29444075
TI  - Correction: The translesion DNA polymerases Pol zeta and Rev1 are activated
      independently of PCNA ubiquitination upon UV radiation in mutants of DNA
      polymerase delta.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1007119.].

PMID- 29444074
TI  - Self-crowding of AMPA receptors in the excitatory postsynaptic density can
      effectuate anomalous receptor sub-diffusion.
AB  - AMPA receptors (AMPARs) and their associations with auxiliary transmembrane
      proteins are bulky structures with large steric-exclusion volumes. Hence, self
      crowding of AMPARs, depending on the local density, may affect their lateral
      diffusion in the postsynaptic membrane as well as in the highly crowded
      postsynaptic density (PSD) at excitatory synapses. Earlier theoretical studies
      considered only the roles of transmembrane obstacles and the AMPAR-binding
      submembranous scaffold proteins in shaping receptor diffusion within PSD. Using
      lattice model of diffusion, the present study investigates the additional impacts
      of self-crowding on the anomalousity and effective diffusion coefficient (Deff)
      of AMPAR diffusion. A recursive algorithm for avoiding false self-blocking during
      diffusion simulation is also proposed. The findings suggest that high density of
      AMPARs in the obstacle-free membrane itself engenders strongly anomalous
      diffusion and severe decline in Deff. Adding transmembrane obstacles to the
      membrane accentuates the anomalousity arising from self-crowding due to the
      reduced free diffusion space. Contrarily, enhanced AMPAR-scaffold binding, either
      through increase in binding strength or scaffold density or both, ameliorates the
      anomalousity resulting from self-crowding. However, binding has differential
      impacts on Deff depending on the receptor density. Increase in binding causes
      consistent decrease in Deff for low and moderate receptor density. For high
      density, binding increases Deff as long as it reduces anomalousity associated
      with intense self-crowding. Given a sufficiently strong binding condition when
      diffusion acquires normal behavior, further increase in binding causes decrease
      in Deff. Supporting earlier experimental observations are mentioned and
      implications of present findings to the experimental observations on AMPAR
      diffusion are also drawn.

PMID- 29444076
TI  - Fragmentation of nest and foraging habitat affects time budgets of solitary bees,
      their fitness and pollination services, depending on traits: Results from an
      individual-based model.
AB  - Solitary bees are important but declining wild pollinators. During daily foraging
      in agricultural landscapes, they encounter a mosaic of patches with nest and
      foraging habitat and unsuitable matrix. It is insufficiently clear how spatial
      allocation of nesting and foraging resources and foraging traits of bees affect
      their daily foraging performance. We investigated potential brood cell
      construction (as proxy of fitness), number of visited flowers, foraging habitat
      visitation and foraging distance (pollination proxies) with the model SOLBEE
      (simulating pollen transport by solitary bees, tested and validated in an earlier
      study), for landscapes varying in landscape fragmentation and spatial allocation
      of nesting and foraging resources. Simulated bees varied in body size and nesting
      preference. We aimed to understand effects of landscape fragmentation and bee
      traits on bee fitness and the pollination services bees provide, as well as
      interactions between them, and the general consequences it has to our
      understanding of the system. This broad scope gives multiple key results. 1) Body
      size determines fitness more than landscape fragmentation, with large bees
      building fewer brood cells. High pollen requirements for large bees and the
      related high time budgets for visiting many flowers may not compensate for faster
      flight speeds and short handling times on flowers, giving them overall a
      disadvantage compared to small bees. 2) Nest preference does affect distribution
      of bees over the landscape, with cavity-nesting bees being restricted to nesting
      along field edges, which inevitably leads to performance reductions.
      Fragmentation mitigates this for cavity-nesting bees through increased edge
      habitat. 3) Landscape fragmentation alone had a relatively small effect on all
      responses. Instead, the local ratio of nest to foraging habitat affected bee
      fitness positively through reduced local competition. The spatial coverage of
      pollination increases steeply in response to this ratio for all bee sizes. The
      nest to foraging habitat ratio, a strong habitat proxy incorporating
      fragmentation could be a promising and practical measure for comparing landscape
      suitability for pollinators. 4) The number of flower visits was hardly affected
      by resource allocation, but predominantly by bee size. 5) In landscapes with the
      highest visitation coverage, bees flew least far, suggesting that these
      pollination proxies are subject to a trade-off between either longer pollen
      transport distances or a better pollination coverage, linked to how nests are
      distributed over the landscape rather than being affected by bee size.

PMID- 29444077
TI  - Peculiar combinations of individually non-pathogenic missense mitochondrial DNA
      variants cause low penetrance Leber's hereditary optic neuropathy.
AB  - We here report on the existence of Leber's hereditary optic neuropathy (LHON)
      associated with peculiar combinations of individually non-pathogenic missense
      mitochondrial DNA (mtDNA) variants, affecting the MT-ND4, MT-ND4L and MT-ND6
      subunit genes of Complex I. The pathogenic potential of these mtDNA haplotypes is
      supported by multiple evidences: first, the LHON phenotype is strictly inherited
      along the maternal line in one very large family; second, the combinations of
      mtDNA variants are unique to the two maternal lineages that are characterized by
      recurrence of LHON; third, the Complex I-dependent respiratory and oxidative
      phosphorylation defect is co-transferred from the proband's fibroblasts into the
      cybrid cell model. Finally, all but one of these missense mtDNA variants cluster
      along the same predicted fourth E-channel deputed to proton translocation within
      the transmembrane domain of Complex I, involving the ND1, ND4L and ND6 subunits.
      Hence, the definition of the pathogenic role of a specific mtDNA mutation becomes
      blurrier than ever and only an accurate evaluation of mitogenome sequence
      variation data from the general population, combined with functional analyses
      using the cybrid cell model, may lead to final validation. Our study conclusively
      shows that even in the absence of a clearly established LHON primary mutation,
      unprecedented combinations of missense mtDNA variants, individually known as
      polymorphisms, may lead to reduced OXPHOS efficiency sufficient to trigger LHON.
      In this context, we introduce a new diagnostic perspective that implies the
      complete sequence analysis of mitogenomes in LHON as mandatory gold standard
      diagnostic approach.

PMID- 29444079
TI  - Sensitive and less invasive confirmatory diagnosis of visceral leishmaniasis in
      Sudan using loop-mediated isothermal amplification (LAMP).
AB  - BACKGROUND: Confirmatory diagnosis of visceral leishmaniasis (VL), as well as
      diagnosis of relapses and test of cure, usually requires examination by
      microscopy of samples collected by invasive means, such as splenic, bone marrow
      or lymph node aspirates. This causes discomfort to patients, with risks of
      bleeding and iatrogenic infections, and requires technical expertise. Molecular
      tests have great potential for diagnosis of VL using peripheral blood, but
      require well-equipped facilities and trained personnel. More user-friendly, and
      field-amenable options are therefore needed. One method that could meet these
      requirements is loop-mediated isothermal amplification (LAMP) using the Loopamp
      Leishmania Detection Kit, which comes as dried down reagents that can be stored
      at room temperature, and allows simple visualization of results.
      METHODOLOGY/PRINCIPAL FINDINGS: The Loopamp Leishmania Detection Kit (Eiken
      Chemical Co., Japan), was evaluated in the diagnosis of VL in Sudan. A total of
      198 VL suspects were tested by microscopy of lymph node aspirates (the reference
      test), direct agglutination test-DAT (in house production) and rK28 antigen-based
      rapid diagnostic test (OnSite Leishmania rK39-Plus, CTK Biotech, USA). LAMP was
      performed on peripheral blood (whole blood and buffy coat) previously processed
      by: i) a direct boil and spin method, and ii) the QIAamp DNA Mini Kit (QIAgen).
      Ninety seven of the VL suspects were confirmed as cases by microscopy of lymph
      node aspirates. The sensitivity and specificity for each of the tests were: rK28
      RDT 98.81% and 100%; DAT 88.10% and 78.22%; LAMP-boil and spin 97.65% and 99.01%;
      LAMP-QIAgen 100% and 99.01%. CONCLUSIONS/SIGNIFICANCE: Due to its simplicity and
      high sensitivity, rK28 RDT can be used first in the diagnostic algorithm for
      primary VL diagnosis, the excellent performance of LAMP using peripheral blood
      indicates that it can be also included in the algorithm for diagnosis of VL as a
      simple test when parasitological confirmatory diagnosis is required in settings
      that are lower than the reference laboratory, avoiding the need for invasive
      lymph node aspiration.

PMID- 29444078
TI  - Multiplex serology for impact evaluation of bed net distribution on burden of
      lymphatic filariasis and four species of human malaria in northern Mozambique.
AB  - BACKGROUND: Universal coverage with long-lasting insecticidal nets (LLINs) is a
      primary control strategy against Plasmodium falciparum malaria. However, its
      impact on the three other main species of human malaria and lymphatic filariasis
      (LF), which share the same vectors in many co-endemic areas, is not as well
      characterized. The recent development of multiplex antibody detection provides
      the opportunity for simultaneous evaluation of the impact of control measures on
      the burden of multiple diseases. METHODOLOGY/PRINCIPAL FINDINGS: Two cross
      sectional household surveys at baseline and one year after a LLIN distribution
      campaign were implemented in Mecuburi and Nacala-a-Velha Districts in Nampula
      Province, Mozambique. Both districts were known to be endemic for LF; both
      received mass drug administration (MDA) with antifilarial drugs during the
      evaluation period. Access to and use of LLINs was recorded, and household members
      were tested with P. falciparum rapid diagnostic tests (RDTs). Dried blood spots
      were collected and analyzed for presence of antibodies to three P. falciparum
      antigens, P. vivax MSP-119, P. ovale MSP-119, P. malariae MSP-119, and three LF
      antigens. Seroconversion rates were calculated and the association between LLIN
      use and post-campaign seropositivity was estimated using multivariate regression.
      The campaign covered 68% (95% CI: 58-77) of the population in Nacala-a-Velha and
      46% (37-56) in Mecuburi. There was no statistically significant change in P.
      falciparum RDT positivity between the two surveys. Population seropositivity at
      baseline ranged from 31-81% for the P. falciparum antigens, 3-4% for P. vivax MSP
      119, 41-43% for P. ovale MSP-119, 46-56% for P. malariae MSP-119, and 37-76% for
      the LF antigens. The seroconversion rate to the LF Bm33 antigen decreased
      significantly in both districts. The seroconversion rate to P. malariae MSP-119
      and the LF Wb123 and Bm14 antigens each decreased significantly in one of the two
      districts. Community LLIN use was associated with a decreased risk of P.
      falciparum RDT positivity, P. falciparum LSA-1 seropositivity, and P. malariae
      MSP-119 seropositivity, but not LF antigen seropositivity.
      CONCLUSIONS/SIGNIFICANCE: The study area noted significant declines in LF
      seropositivity, but these were not associated with LLIN use. The MDA could have
      masked any impact of the LLINs on population LF seropositivity. The LLIN campaign
      did not reach adequately high coverage to decrease P. falciparum RDT positivity,
      the most common measure of P. falciparum burden. However, the significant
      decreases in the seroconversion rate to the P. malariae antigen, coupled with an
      association between community LLIN use and individual-level decreases in
      seropositivity to P. falciparum and P. malariae antigens show evidence of impact
      of the LLIN campaign and highlight the utility of using multiantigenic
      serological approaches for measuring intervention impact.

PMID- 29444080
TI  - Promising approach to reducing Malaria transmission by ivermectin: Sporontocidal
      effect against Plasmodium vivax in the South American vectors Anopheles aquasalis
      and Anopheles darlingi.
AB  - BACKGROUND: The mosquito resistance to the insecticides threatens malaria control
      efforts, potentially becoming a major public health issue. Alternative methods
      like ivermectin (IVM) administration to humans has been suggested as a possible
      vector control to reduce Plasmodium transmission. Anopheles aquasalis and
      Anopheles darlingi are competent vectors for Plasmodium vivax, and they have been
      responsible for various malaria outbreaks in the coast of Brazil and the Amazon
      Region of South America. METHODS: To determine the IVM susceptibility against P.
      vivax in An. aquasalis and An. darlingi, ivermectin were mixed in P. vivax
      infected blood: (1) Powdered IVM at four concentrations (0, 5, 10, 20 or 40
      ng/mL). (2) Plasma (0 hours, 4 hours, 1 day, 5, 10 and 14 days) was collected
      from healthy volunteers after to administer a single oral dose of IVM (200
      MUg/kg) (3) Mosquitoes infected with P. vivax and after 4 days was provided with
      IVM plasma collected 4 hours post-treatment (4) P. vivax-infected patients were
      treated with various combinations of IVM, chloroquine, and primaquine and plasma
      or whole blood was collected at 4 hours. Seven days after the infective blood
      meal, mosquitoes were dissected to evaluate oocyst presence. Additionally, the ex
      vivo effects of IVM against asexual blood-stage P. vivax was evaluated. RESULTS:
      IVM significantly reduced the prevalence of An. aquasalis that developed oocysts
      in 10 to 40 ng/mL pIVM concentrations and plasma 4 hours, 1 day and 5 days. In
      An. darlingi to 4 hours and 1 day. The An. aquasalis mortality was expressively
      increased in pIVM (40ng/mL) and plasma 4 hours, 1, 5 10 and 14 days post-intake
      drug and in An. darlingi only to 4 hours and 1 day. The double fed meal with mIVM
      by the mosquitoes has a considerable impact on the proportion of infected
      mosquitoes for 7 days post-feeding. The oocyst infection prevalence and intensity
      were notably reduced when mosquitoes ingested blood from P. vivax patients that
      ingested IVM+CQ, PQ+CQ and IVM+PQ+CQ. P. vivax asexual development was
      considerably inhibited by mIVM at four-fold dilutions. CONCLUSION: In conclusion,
      whole blood spiked with IVM reduced the infection rate of P. vivax in An.
      aquasalis and An. darlingi, and increased the mortality of mosquitoes. Plasma
      from healthy volunteers after IVM administration affect asexual P. vivax
      development. These findings support that ivermectin may be used to decrease P.
      vivax transmission.

PMID- 29444081
TI  - Alpha desynchronization/synchronization during working memory testing is
      compromised in acute mild traumatic brain injury (mTBI).
AB  - Diagnosing and monitoring recovery of patients with mild traumatic brain injury
      (mTBI) is challenging because of the lack of objective, quantitative measures.
      Diagnosis is based on description of injuries often not witnessed, subtle
      neurocognitive symptoms, and neuropsychological testing. Since working memory
      (WM) is at the center of cognitive functions impaired in mTBI, this study was
      designed to define objective quantitative electroencephalographic (qEEG) measures
      of WM processing that may correlate with cognitive changes associated with acute
      mTBI. First-time mTBI patients and mild peripheral (limb) trauma controls without
      head injury were recruited from the emergency department. WM was assessed by a
      continuous performance task (N-back). EEG recordings were obtained during N-back
      testing on three occasions: within five days, two weeks, and one month after
      injury. Compared with controls, mTBI patients showed abnormal induced and evoked
      alpha activity including event-related desynchronization (ERD) and
      synchronization (ERS). For induced alpha power, TBI patients had excessive
      frontal ERD on their first and third visit. For evoked alpha, mTBI patients had
      lower parietal ERD/ERS at the second and third visits. These exploratory qEEG
      findings offer new and non-invasive candidate measures to characterize the
      evolution of injury over the first month, with potential to provide much-needed
      objective measures of brain dysfunction to diagnose and monitor the consequences
      of mTBI.

PMID- 29444082
TI  - S100B as an antagonist to block the interaction between S100A1 and the RAGE V
      domain.
AB  - Ca2+-binding human S100A1 protein is a type of S100 protein. S100A1 is a
      significant mediator during inflammation when Ca2+ binds to its EF-hand motifs.
      Receptors for advanced glycation end products (RAGE) correspond to 5 domains: the
      cytoplasmic, transmembrane, C2, C1, and V domains. The V domain of RAGE is one of
      the most important target proteins for S100A1. It binds to the hydrophobic
      surface and triggers signaling transduction cascades that induce cell growth,
      cell proliferation, and tumorigenesis. We used nuclear magnetic resonance (NMR)
      spectroscopy to characterize the interaction between S100A1 and the RAGE V
      domain. We found that S100B could interact with S100A1 via NMR 1H-15N HSQC
      titrations. We used the HADDOCK program to generate the following two binary
      complexes based on the NMR titration results: S100A1-RAGE V domain and S100A1
      S100B. After overlapping these two complex structures, we found that S100B plays
      a crucial role in blocking the interaction site between RAGE V domain and S100A1.
      A cell proliferation assay WST-1 also supported our results. This report could
      potentially be useful for new protein development for cancer treatment.

PMID- 29444083
TI  - High fat diet sensitizes fibromyalgia-like pain behaviors in mice via tumor
      necrosis factor alpha.
AB  - Fibromyalgia (FM) and obesity are closely related. However, little is known about
      how obesity contributes to FM. Importantly, adequate evidence has shown that
      tumor necrosis factor alpha (TNF-alpha) plays a critical role in obesity. Thus,
      we hypothesized that obesity-induced TNF-alpha release may potentiate FM
      associated pain. To test this hypothesis, we investigated the role of TNF-alpha
      in the development of FM-like pain in a mouse model of acid saline injection
      induced FM. Consistent with previous reports, we showed that repeated acid saline
      injections induced bilateral mechanical hyperalgesia, and this effect lasted for
      at least 4 days after acid saline injections. This phenomenon was associated with
      increased levels of TNF-alpha in plasma, muscles, and spinal cord. Furthermore,
      we found that 24 weeks of high fat diet treatment significantly potentiated acid
      saline-induced bilateral mechanical hyperalgesia. High fat diet-treated mice
      exhibited robustly increased levels of TNF-alpha in plasma, muscles, and spinal
      cord after acid saline injections compared with low fat diet-treated mice.
      Additionally, using immunofluorescence staining, we found that the number of TNF
      alpha positive cells in dorsal root ganglion (DRG) was increased after acid
      saline injections, and high fat diet treatment further sensitized this increase.
      Finally, we reported that acid saline-induced FM-like pain behaviors were
      abolished in TNFRp55-/- mice, confirming the critical role of TNF-alpha in the
      development of FM-like pain. Taken together, our results suggested that high fat
      diet treatment may sensitize acid saline-induced FM-like pain via increasing TNF
      alpha levels in plasma, muscles, and DRG.

PMID- 29444084
TI  - Attributional style and depressive symptoms in a male prison sample.
AB  - The reformulated learned helplessness model proposes that people who tend to make
      internal, stable, and global attributions in response to uncontrollable aversive
      events are more likely to develop depression. The present study sought to
      investigate the nature of the relationship between attributional style and
      depression in a male prison sample. One hundred and one adult male prisoners from
      four medium security prisons in Ireland completed the Attributional Style
      Questionnaire and measures of depression (BDI-II) and anxiety (BAI). Severity of
      self-reported depressive symptoms in the present sample was comparable to other
      prison and clinical samples, but higher than community samples. Participants were
      more severely affected by depressive symptoms than anxiety. The original
      attributional dimensions (i.e. internal, stable, and global) predicted a
      significant amount of variance in depression, but the model was not significant
      after controlling for anxiety. A subsequent regression model, comprising
      attributional dimensions for both negative events and positive events including a
      measure of 'uncontrollability', accounted for 35% of the variance in depression
      and the model retained significance while controlling for anxiety. An
      attributional model of depression may be relevant to the prison population and
      could provide a valid insight into the development and treatment of depressive
      symptoms in prisoners. The findings are interpreted in relation to previous
      research and implications for theory, clinical practice, and rehabilitation are
      discussed.

PMID- 29444085
TI  - Correction: Mendelian and Non-Mendelian Regulation of Gene Expression in Maize.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1003202.].

PMID- 29444086
TI  - Mapping human vulnerability to climate change in the Brazilian Amazon: The
      construction of a municipal vulnerability index.
AB  - Vulnerability, understood as the propensity to be adversely affected, has
      attained importance in the context of climate change by helping to understand
      what makes populations and territories predisposed to its impacts. Conditions of
      vulnerability may vary depending on the characteristics of each territory studied
      social, environmental, infrastructural, public policies, among others. Thus, the
      present study aimed to evaluate what makes the municipalities of the state of
      Amazonas, Brazil, vulnerable to climate change in the context of the largest
      tropical forest in the world, and which regions of the State are the most
      susceptible. A Municipal Vulnerability Index was developed, which was used to
      associate current socio-environmental characteristics of municipalities with
      climate change scenarios in order to identify those that may be most affected by
      climate change. The results showed that poor adaptive capacity and poverty had
      the most influence on current vulnerability of the municipalities of Amazonas
      with the most vulnerable areas being the southern, northern, and eastern regions
      of the state. When current vulnerability was related to future climate change
      projections, the most vulnerable areas were the northern, northeastern, extreme
      southern, and southwestern regions. From a socio-environmental and climatic point
      of view, these regions should be a priority for public policy efforts to reduce
      their vulnerability and prepare them to cope with the adverse aspects of climate
      change.

PMID- 29444088
TI  - Correction: The Compartmentalized Bacteria of the Planctomycetes-Verrucomicrobia
      Chlamydiae Superphylum Have Membrane Coat-Like Proteins.
AB  - [This corrects the article DOI: 10.1371/journal.pbio.1000281.].

PMID- 29444087
TI  - Safety and efficacy of anti-PD-L1 therapy in the woodchuck model of HBV
      infection.
AB  - Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust
      antiviral T cell responses, while virus-specific T cells in chronic hepatitis B
      (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD
      1) expression on virus-specific T cells. Thus, an immunotherapy able to expand
      and activate virus-specific T cells may have therapeutic benefit for CHB
      patients. Like HBV-infected patients, woodchucks infected with woodchuck
      hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD
      L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T
      cells with substantial individual variation in these parameters. We used
      woodchucks infected with WHV to assess the safety and efficacy of anti-PD-L1
      monoclonal antibody therapy (alphaPD-L1) in a variety of WHV infection states.
      Experimentally-infected animals lacked PD-1 or PD-L1 upregulation compared to
      uninfected controls, and accordingly, alphaPD-L1 treatment in lab-infected
      animals had limited antiviral effects. In contrast, animals with naturally
      acquired WHV infections displayed elevated PD-1 and PD-L1. In these same animals,
      combination therapy with alphaPD-L1 and entecavir (ETV) improved control of
      viremia and antigenemia compared to ETV treatment alone, but with efficacy
      restricted to a minority of animals. Pre-treatment WHV surface antigen (sAg)
      level was identified as a statistically significant predictor of treatment
      response, while PD-1 expression on peripheral CD8+ T cells, T cell production of
      interferon gamma (IFN-gamma) upon in vitro antigen stimulation (WHV ELISPOT), and
      circulating levels of liver enzymes were not. To further assess the safety of
      this strategy, alphaPD-L1 was tested in acute WHV infection to model the risk of
      liver damage when the extent of hepatic infection and antiviral immune responses
      were expected to be the greatest. No significant increase in serum markers of
      hepatic injury was observed over those in infected, untreated control animals.
      These data support a positive benefit/risk assessment for blockade of the PD-1:PD
      L1 pathway in CHB patients and may help to identify patient groups most likely to
      benefit from treatment. Furthermore, the efficacy of alphaPD-L1 in only a
      minority of animals, as observed here, suggests that additional agents may be
      needed to achieve a more robust and consistent response leading to full sAg loss
      and durable responses through anti-sAg antibody seroconversion.

PMID- 29444089
TI  - Evaluation of Proctophyllodes huitzilopochtlii on feathers from Anna's (Calypte
      anna) and Black-chinned (Archilochus alexandri) Hummingbirds: Prevalence
      assessment and imaging analysis using light and tabletop scanning electron
      microscopy.
AB  - Proctophyllodes huitzilopochtlii Atyeo & Braasch 1966 (Acariformes: Astigmata:
      Proctophyllodidae), a feather mite, was found on feathers collected from five
      hummingbird species in California. This mite has not been previously documented
      on feathers from Anna's (Calypte anna [Lesson 1829]) or Black-chinned
      (Archilochus alexandri [Bourcier & Mulsant 1846]) Hummingbirds. A total of 753
      hummingbirds were evaluated for the presence of mites by species (Allen's n =
      112; Anna's n = 500; Black-chinned n = 122; Rufous n = 18; Calliope n = 1), sex
      (males n = 421; females n = 329; 3 unidentified), and age (juvenile n = 199;
      after-hatch-year n = 549; 5 unidentified). Of these 753 hummingbirds evaluated,
      mites were present on the rectrices of 40.9% of the birds. Significantly more
      Anna's Hummingbirds were positive for rectricial mites (59.2%) compared with 8.2%
      of Black-chinned, 0.9% of Allen's, 5.6% of Rufous Hummingbirds, and 0% for
      Calliope (p-value < 0.0001). Across all hummingbird species, male hummingbirds
      (44.9%) had a higher prevalence of rectricial mites compared to female
      hummingbirds (36.2%; p-value = 0.004), while juvenile hummingbirds (46.2%) had a
      non-significantly higher prevalence compared to after-hatch-year hummingbirds
      (39.0%; p-value = 0.089). On average, the percentage of the long axis of the
      rachis occupied by mites for the outer rectrices (R4 and R5) was 19%, compared to
      11% for inner rectrices (R1 and R2), a significant difference (p-value =
      <0.0001). There was a marginal lack of significance for symmetrical distribution
      of tail mites with the mean left side percentage of long axis of the rachis
      occupied by mites being 16% and very close to the mean right side score of 18% (p
      value = 0.003). The identification of the feather mite species was based on light
      microscopic morphometry, and mite distribution on feathers was further evaluated
      using tabletop scanning electron microscopy (TSEM). The hummingbird-feather mite
      relationship is not well understood, but the specialized TSEM technique may be
      especially useful in examining natural positioning and developmental aspects of
      the mites since it allows in situ feather examination of live mites.

PMID- 29444090
TI  - Identification of FAM173B as a protein methyltransferase promoting chronic pain.
AB  - Chronic pain is a debilitating problem, and insights in the neurobiology of
      chronic pain are needed for the development of novel pain therapies. A genome
      wide association study implicated the 5p15.2 region in chronic widespread pain.
      This region includes the coding region for FAM173B, a functionally
      uncharacterized protein. We demonstrate here that FAM173B is a mitochondrial
      lysine methyltransferase that promotes chronic pain. Knockdown and sensory neuron
      overexpression strategies showed that FAM173B is involved in persistent
      inflammatory and neuropathic pain via a pathway dependent on its
      methyltransferase activity. FAM173B methyltransferase activity in sensory neurons
      hyperpolarized mitochondria and promoted macrophage/microglia activation through
      a reactive oxygen species-dependent pathway. In summary, we uncover a role for
      methyltransferase activity of FAM173B in the neurobiology of pain. These results
      also highlight FAM173B methyltransferase activity as a potential therapeutic
      target to treat debilitating chronic pain conditions.

PMID- 29444091
TI  - A comprehensive meta-analysis of circulation miRNAs in glioma as potential
      diagnostic biomarker.
AB  - Glioma is the most common malignant intracranial tumour. Recently, several
      publications have suggested that miRNAs can be used as potential diagnostic
      biomarkers of glioma. Here we performed a meta-analysis to identify the
      diagnostic accuracy of differentially expressed circulating miRNAs in gliomas.
      Using PubMed, Medline and Cochrane databases, we searched for studies which
      evaluated a single or panel of miRNAs from circulating blood as potential
      biomarkers of glioma. Sixteen publications involving 23 studies of miRNAs from
      serum or plasma met our criteria and were included in this meta-analysis. The
      pooled diagnostic parameters were calculated by random effect models and overall
      diagnostic performance of altered miRNAs was illustrated by the summary receiver
      operator characteristic (SROC) curves. The pooled sensitivity, specificity,
      positive likelihood ratio (PLR) and negative likelihood ratio (NLR) from each
      study were calculated. The pooled PLR, NLR and Diagnostic Odds Ratio were 6.39
      (95% CI, 4.61-8.87), 0.15 (95% CI, 0.11-0.21) and 41.91 (95% CI, 23.15-75.88),
      respectively. The pooled sensitivity, specificity and area under the curve (AUC)
      were 0.87 (95% CI, 0.82-0.91), 0.86 (95% CI, 0.82-0.90) and 0.93 (95% CI, 0.91
      0.95), respectively. This meta-analysis demonstrated that circulating miRNAs are
      capable of distinguishing glioma from healthy controls. Circulating miRNAs are
      promising diagnostic biomarkers for glioma and can potentially be used as a non
      invasive early detection.

PMID- 29444092
TI  - The impact of early life nutrition and housing on growth and reproduction in
      dairy cattle.
AB  - Contentious issues in calf rearing include milk feeding practices and single
      versus group housing. The current study was performed on a high producing 170
      Holstein cow dairy farm, to investigate the impact of nutrition and housing on
      growth and reproduction. Heifer calves (n = 100) were allocated in birth order to
      one of two commonly used management strategies. All calves received 3-4 litres of
      dam specific colostrum within 6 hours of birth. Group A calves were group housed
      from birth and fed milk replacer (MR) ad libitum via a computerised machine
      utilising a single teat, with weaning commencing at 63 days of age. Group R
      calves were initially housed in individual pens and received 2.5 litres of MR
      twice daily via a bucket until 21 days of age when they were group housed and fed
      3 litres of MR twice daily via a group trough with weaning commencing at 56 days.
      From 12 weeks of age onwards, calves in both dietary groups were subject to
      common nutritional and husbandry protocols. All breeding of heifers was via
      artificial insemination with no hormonal intervention. Calves were weighed, body
      condition scored and morphometric measures recorded weekly up till 12 weeks of
      age then monthly until conception. Pre-weaning growth rates (kg/day) were
      significantly higher in Group A calves compared to Group R (0.89, 95% CI 0.86
      0.93 vs 0.57, 95% CI 0.54-0.6 kg/day P < 0.001) with the most marked differences
      observed during the first three weeks of life (0.72, 95% CI 0.61-0.82 vs 0.17,
      95% CI 0.08-0.26 P < 0.001). Whilst Group A calves gained body condition score
      (BCS) throughout the pre-weaning phase, Group R calves lost BCS during the first
      4 weeks of life. Data suggested that Group R calves supported skeletal growth
      during this period by catabolising body tissue. Group A calves had a greater risk
      of disease than group R calves during the pre-weaning phase (diarrhoea: odds
      ratio 3.86, 95% CI 1.67-8.9; pneumonia: odds ratio 5.80, 95% CI 2.33-14.44)
      although no calves died during this period. Whilst pneumonia had a significant
      impact on growth during the study duration (P = 0.008), this was not the case for
      diarrhoea. Whilst univariate analysis failed to show any statistically
      significant group differences (P > 0.050) in any of the mean values of measured
      reproductive parameters, multivariable Cox regression suggested that there was a
      weak trend (P = 0.072) for Group A animals to achieve first service earlier than
      their Group R counterparts (62.6 weeks versus 65.3 weeks). Irrespective of
      dietary group, the hazard for achievement of all measured reproductive
      parameters, apart from time to puberty, was 20-40% less for heifers borne from
      multiparous dams compared to heifers from primiparous dams.

PMID- 29444093
TI  - The high prevalence of playing-related musculoskeletal disorders (PRMDs) and its
      associated factors in amateur musicians playing in student orchestras: A cross
      sectional study.
AB  - OBJECTIVE: Despite the high number of amateur musicians in the general
      population, little is known about the musculoskeletal health of amateur
      musicians. Playing a musical instrument is supposed to be a risk factor for the
      development of musculoskeletal complaints. This study aimed to evaluate playing
      related musculoskeletal disorders (PRMDs) among amateur musicians playing in
      student orchestras. DESIGN: A cross-sectional study. PARTICIPANTS: 357 members of
      eleven Dutch student orchestras across the Netherlands were included in this
      study. INTERVENTION: A paper-based questionnaire on PRMDs was used. OUTCOME
      MEASURES: Sociodemographic characteristics and PRMDs were evaluated using an
      adaptation of the Nordic Musculoskeletal Questionnaire (NMQ) and the music module
      of the Disabilities of Shoulder and Hand (DASH) questionnaire. RESULTS: The year
      prevalence of PRMDs among amateur musicians was 67.8%. Female gender, younger
      age, higher BMI and playing a string instrument were independently associated
      with a higher prevalence of PRMDs. The left shoulder was affected more frequently
      in violinists and violists, whereas the right hand and wrist were more frequently
      affected in woodwind instrumentalists. Of the subjects with PRMDs during the last
      week, the score of the music module of the DASH was 18.8 (6.3-31.2). DISCUSSION:
      This study is the first to report on PRMDs and its associated factors in a large
      group of amateur musicians. The prevalence of PRMDs in amateur musicians is high,
      however the DASH scores reflect a confined impact of these PRMDs on their
      functioning as a musician. Preventive measures are needed aiming at reducing
      PRMDs among amateur musicians.

PMID- 29444094
TI  - Plate waste of adults in the United States measured in free-living conditions.
AB  - We analyze food-item level data collected from 50 adults from the United States
      using the Remote Food Photography Method(r) to provide the first estimates of
      plate waste gathered from adults across multiple consecutive meals and days in
      free-living conditions, and during laboratory-based meals with fixed food items
      and quantities. We find average plate waste in free-living conditions is 5.6
      grams (7.7 kcals) per item and that 3.3% of all food selected is returned as
      plate waste, where the percent waste figure is substantially lower than
      previously published plate waste estimates gathered primarily from dine-out
      settings in the United States such as buffets and institutional settings with
      limited-choice meals (e.g., school cafeterias). Plate waste from the same
      participants during the laboratory-based meals is significantly higher with an
      average of 203.2 grams of solid plate waste per meal (531.3 kcals) or 39.1% of
      the food provided, which is similar to the plate waste percentages found reported
      in some school cafeteria settings. The amount of plate waste generated in free
      living conditions is significantly positively associated with portion size
      selected for an item. In a multivariate analysis that controls for macronutrient
      profile, items selected from the vegetables, fats/oils/dressings, and grains
      categories are associated with significantly greater amounts of plate waste per
      item. We find no significant associations between free-living plate waste and
      gender, age, race or body mass index but find that women leave more plate waste
      in the lab meal where portion sizes are pre-determined by the researcher and
      similar for all respondents. We discuss possible implications of these findings
      for programs focused on reducing plate waste and food waste among consumers.

PMID- 29444095
TI  - Social class, social mobility and alcohol-related disorders in Swedish men and
      women: A study of four generations.
AB  - OBJECTIVES: To investigate whether and how social class and social mobility in
      grandparents and parents predict alcohol-related disorders (ARDs) in males and
      females aged 12+ years, and whether intergenerational social prediction of ARDs
      varies across time periods. METHODS: The study sample included four successive
      generations (G) of Swedish families from the Uppsala Birth Cohort
      Multigenerational Study: G0 born 1851-1912; G1 born 1915-1929; G2 born 1940-1964
      and G3 born 1965-1989. Two study populations were created, each consisting of
      grandparents, parents and offspring: population I 'G0-G1-G2' (offspring n = 18
      430) and population II 'G1-G2-G3' (offspring n = 26 469). Registers and archives
      provided data on ancestors' socio-demographic factors and ARD history, together
      with offspring ARD development between 1964-2008. Cox regression models examined
      the hazard of offspring ARD development according to grandparental social class
      and grandparental-to-parental social trajectories, controlling for offspring
      birth year, grandmother's and mother's marital status and parental ARDs. RESULTS:
      Disadvantaged grandparental social class predicted increased ARD risk in
      offspring in population I, although the effect attenuated and became non
      significant in males after adjusting for parental characteristics (adjusted
      hazard ratio (HR) = 1.80 (95%CI; 1.07, 3.03) in females, HR = 1.32 (95%CI; 0.93,
      1.89) in males). In population II, no increase in ARD risk by grandparental
      social was evident. In both populations, males were at the highest ARD risk if
      both parents and grandparents belonged to disadvantaged social class (population
      I: HR = 1.82 (95%CI; 1.22-2.72); population II: HR = 1.68 (95%CI; 1.02-2.76)).
      CONCLUSIONS: Intergenerational social patterning of ARDs appears to be time
      contextual and gender-specific. The role of grandparental social class in
      developing ARDs in grandchildren seems to decline over time, while persistent
      grandparental-to-parental social disadvantage remains associated with higher ARD
      risk in males. When targeting higher risk groups, continuity of familial social
      disadvantage, particularly among males, should be considered.

PMID- 29444096
TI  - Invasive African clawed frogs in California: A reservoir for or predator against
      the chytrid fungus?
AB  - Amphibian species are experiencing population declines due to infection by the
      fungal pathogen, Batrachochytrium dendrobatidis (Bd). The African clawed frog
      (Xenopus laevis), an asymptomatic carrier of Bd, has been implicated in the
      spread of this pathogen through global trade and established invasive populations
      on several continents. However, research has not explored the relationships of
      both life stages of this amphibian with Bd. While the post-metamorphic
      individuals may act as a reservoir, spreading the infection to susceptible
      species, the filter-feeding larvae may consume the motile Bd zoospores from the
      water column, potentially reducing pathogen abundance and thus the likelihood of
      infection. We explore these contrasting processes by assessing Bd prevalence and
      infection intensities in field populations of post-metamorphic individuals, and
      performing laboratory experiments to determine if larval X. laevis preyed upon Bd
      zoospores. The water flea, Daphnia magna, was included in the Bd consumption
      trials to compare consumption rates and to explore whether intraguild predation
      between the larval X. laevis and Daphnia may occur, potentially interfering with
      control of Bd zoospores by Daphnia. Field surveys of three X. laevis populations
      in southern California, in which 70 post-metamorphic individuals were tested for
      Bd, found 10% infection prevalence. All infected individuals had very low
      infection loads (all Bd loads were below 5 zoospore equivalents). Laboratory
      experiments found that larval X. laevis consume Bd zoospores and therefore may
      reduce Bd abundance and transmission between amphibians. However, metamorphic and
      juvenile X. laevis exhibited intraguild predation by consuming Daphnia, which
      also prey upon Bd zoospores. The results suggest that X laevis is not a large
      reservoir for Bd and its larval stage may offer some reduction of Bd transmission
      through direct predation.

PMID- 29444097
TI  - The effects of intensified training on resting metabolic rate (RMR), body
      composition and performance in trained cyclists.
AB  - BACKGROUND: Recent research has demonstrated decreases in resting metabolic rate
      (RMR), body composition and performance following a period of intensified
      training in elite athletes, however the underlying mechanisms of change remain
      unclear. Therefore, the aim of the present study was to investigate how an
      intensified training period, designed to elicit overreaching, affects RMR, body
      composition, and performance in trained endurance athletes, and to elucidate
      underlying mechanisms. METHOD: Thirteen (n = 13) trained male cyclists completed
      a six-week training program consisting of a "Baseline" week (100% of regular
      training load), a "Build" week (~120% of Baseline load), two "Loading" weeks
      (~140, 150% of Baseline load, respectively) and two "Recovery" weeks (~80% of
      Baseline load). Training comprised of a combination of laboratory based interval
      sessions and on-road cycling. RMR, body composition, energy intake, appetite,
      heart rate variability (HRV), cycling performance, biochemical markers and mood
      responses were assessed at multiple time points throughout the six-week period.
      Data were analysed using a linear mixed modeling approach. RESULTS: The
      intensified training period elicited significant decreases in RMR (F(5,123.36) =
      12.0947, p = <0.001), body mass (F(2,19.242) = 4.3362, p = 0.03), fat mass
      (F(2,20.35) = 56.2494, p = <0.001) and HRV (F(2,22.608) = 6.5212, p = 0.005); all
      of which improved following a period of recovery. A state of overreaching was
      induced, as identified by a reduction in anaerobic performance (F(5,121.87) =
      8.2622, p = <0.001), aerobic performance (F(5,118.26) = 2.766, p = 0.02) and
      increase in total mood disturbance (F(5, 110.61) = 8.1159, p = <0.001).
      CONCLUSION: Intensified training periods elicit greater energy demands in trained
      cyclists, which, if not sufficiently compensated with increased dietary intake,
      appears to provoke a cascade of metabolic, hormonal and neural responses in an
      attempt to restore homeostasis and conserve energy. The proactive monitoring of
      energy intake, power output, mood state, body mass and HRV during intensified
      training periods may alleviate fatigue and attenuate the observed decrease in
      RMR, providing more optimal conditions for a positive training adaptation.

PMID- 29444098
TI  - Integrating nutrient bioavailability and co-production links when identifying
      sustainable diets: How low should we reduce meat consumption?
AB  - BACKGROUND: Reducing the consumption of meat and other animal-based products is
      widely advocated to improve the sustainability of diets in high-income countries.
      However, such reduction may impair nutritional adequacy, since the
      bioavailability of key nutrients is higher when they come from animal- vs plant
      based foods. Meat reduction may also affect the balance between foods co-produced
      within the same animal production system. OBJECTIVE: The objective was to assess
      the impact of introducing nutrient bioavailability and co-production links
      considerations on the dietary changes needed - especially regarding meat - to
      improve diet sustainability. METHODS: Diet optimization with linear and non
      linear programming was used to design, for each gender, three modeled diets
      departing the least from the mean observed French diet (OBS) while reducing by at
      least 30% the diet-related environmental impacts (greenhouse gas emissions,
      eutrophication, acidification): i) in the nutrition-environment (NE) model, the
      fulfillment of recommended dietary allowances for all nutrients was imposed; ii)
      in the NE-bioavailability (NEB) model, nutritional adequacy was further ensured
      by accounting for iron, zinc, protein and provitamin A bioavailability; iii) in
      the NEB-co-production (NEB-CP) model, two links between co-produced animal foods
      (milk-beef and blood sausage-pork) were additionally included into the models by
      proportionally co-constraining their respective quantities. The price and
      environmental impacts of individual foods were assumed to be constant. RESULTS:
      'Fruit and vegetables' and 'Starches' quantities increased in all modeled diets
      compared to OBS. In parallel, total meat and ruminant meat quantities decreased.
      Starting from 110g/d women's OBS diet (168g/d for men), total meat quantity
      decreased by 78%, 67% and 32% for women (68%, 66% and 62% for men) in NE, NEB and
      NEB-CP diets, respectively. Starting from 36g/d women's OBS diet (54g/d for men),
      ruminant meat quantity dropped severely by 84% and 87% in NE and NEB diets for
      women (80% and 78% for men), whereas it only decreased by 27% in NEB-CP diets
      (38% for men). The share of energy and proteins of animal origin was similar for
      the 3 modeled diets (approximately 1/5 of total energy, and 1/2 of protein) and
      lower than in OBS diet (approximately 1/3 of total energy, and 2/3 of protein).
      CONCLUSIONS: Decreasing meat content was strictly needed to achieve more
      sustainable diets for French adults, but the reduction was less severe when
      nutrient bioavailability and co-production links were taken into account.

PMID- 29444099
TI  - Airway ciliary dysfunction and respiratory symptoms in patients with
      transposition of the great arteries.
AB  - BACKGROUND: Our prior work on congenital heart disease (CHD) with heterotaxy, a
      birth defect involving randomized left-right patterning, has shown an association
      of a high prevalence of airway ciliary dysfunction (CD; 18/43 or 42%) with
      increased respiratory symptoms. Furthermore, heterotaxy patients with ciliary
      dysfunction were shown to have more postsurgical pulmonary morbidities. These
      findings are likely a reflection of the common role of motile cilia in both
      airway clearance and left-right patterning. As CHD comprising transposition of
      the great arteries (TGA) is commonly thought to involve disturbance of left-right
      patterning, especially L-TGA with left-right ventricular inversion, we
      hypothesize CHD patients with transposition of great arteries (TGA) may have high
      prevalence of airway CD with increased respiratory symptoms. METHODS AND RESULTS:
      We recruited 75 CHD patients with isolated TGA, 28% L and 72% D-TGA. Patients
      were assessed using two tests typically used for evaluating airway ciliary
      dysfunction in patients with primary ciliary dyskinesia (PCD), a recessive
      sinopulmonary disease caused by respiratory ciliary dysfunction. This entailed
      the measurement of nasal nitric oxide (nNO), which is typically low with PCD. We
      also obtained nasal scrapes and conducted videomicroscopy to assess respiratory
      ciliary motion (CM). We observed low nNO in 29% of the patients, and abnormal CM
      in 57%, with 22% showing both low nNO and abnormal CM. No difference was observed
      for the prevalence of either low nNO or abnormal ciliary motion between patients
      with D vs. L-TGA. Respiratory symptoms were increased with abnormal CM, but not
      low nNO. Sequencing analysis showed no compound heterozygous or homozygous
      mutations in 39 genes known to cause PCD, nor in CFTR, gene causing cystic
      fibrosis. As both are recessive disorders, these results indicate TGA patients
      with ciliary dysfunction do not have PCD or cystic fibrosis (which can cause low
      nNO or abnormal ciliary motion). CONCLUSIONS: TGA patients have high prevalence
      of abnormal CM and low nNO, but ciliary dysfunction was not correlated with TGA
      type. Differing from PCD, respiratory symptoms were increased with abnormal CM,
      but not low nNO. Together with the negative findings from exome sequencing
      analysis, this would suggest TGA patients with ciliary dysfunction do not have
      PCD but nevertheless may suffer from milder airway clearance deficiency. Further
      studies are needed to investigate whether such ciliary dysfunction is associated
      with increased postsurgical complications as previously observed in CHD patients
      with heterotaxy.

PMID- 29444100
TI  - Super-ranging. A new ranging strategy in European badgers.
AB  - We monitored the ranging of a wild European badger (Meles meles) population over
      7 years using GPS tracking collars. Badger range sizes varied seasonally and
      reached their maximum in June, July and August. We analysed the summer ranging
      behaviour, using 83 home range estimates from 48 individuals over 6974 collar
      nights. We found that while most adult badgers (males and females) remained
      within their own traditional social group boundaries, several male badgers (on
      average 22%) regularly ranged beyond these traditional boundaries. These adult
      males frequently ranged throughout two (or more) social group's traditional
      territories and had extremely large home ranges. We therefore refer to them as
      super-rangers. While ranging across traditional boundaries has been recorded over
      short periods of time for extraterritorial mating and foraging forays, or for pre
      dispersal exploration, the animals in this study maintained their super-ranges
      from 2 to 36 months. This study represents the first time such long-term extra
      territorial ranging has been described for European badgers. Holding a super
      range may confer an advantage in access to breeding females, but could also
      affect local interaction networks. In Ireland & the UK, badgers act as a wildlife
      reservoir for bovine tuberculosis (TB). Super-ranging may facilitate the spread
      of disease by increasing both direct interactions between conspecifics,
      particularly across social groups, and indirect interactions with cattle in their
      shared environment. Understanding super-ranging behaviour may both improve our
      understanding of tuberculosis epidemiology and inform future control strategies.

PMID- 29444101
TI  - Development and characterization of two cell lines from gills of Atlantic salmon.
AB  - Gill disease in Atlantic salmon, Salmo salar L., causes big losses in the salmon
      farming industry. Until now, tools to cultivate microorganisms causing gill
      disease and models to study the gill responses have been lacking. Here we
      describe the establishment and characterization of two cell lines from the gills
      of Atlantic salmon. Atlantic salmon gill cell ASG-10 consisted of cells staining
      for cytokeratin and e-cadherin and with desmosomes as seen by transmission
      electron microscopy suggesting the cells to be of epithelial origin. These
      structures were not seen in ASG-13. The cell lines have been maintained for
      almost 30 passages and both cell lines are fully susceptible to infection by
      infectious hematopoietic necrosis virus (IHNV), viral hemorrhagic septicemia
      virus (VHSV), infectious pancreatic necrosis virus (IPNV), Atlantic salmon
      reovirus TS (TSRV) and Pacific salmon paramyxovirus (PSPV). While infectious
      salmon anemia virus (ISAV) did not cause visible CPE, immunofluorescent staining
      revealed a sub-fraction of cells in both the ASG-10 and ASG-13 lines may be
      permissive to infection. ASG-10 is able to proliferate and migrate to close
      scratches in the monolayer within seven days in vitro contrary to ASG-13, which
      does not appear to do have the same proliferative and migratory ability. These
      cell lines will be useful in studies of gill diseases in Atlantic salmon and may
      represent an important contribution for alternatives to experimental animals and
      studies of epithelial-mesenchymal cell biology.

PMID- 29444102
TI  - Parallel behavioral and morphological divergence in fence lizards on two college
      campuses.
AB  - The spread of urban development has dramatically altered natural habitats,
      modifying community relationships, abiotic factors, and structural features.
      Animal populations living in these areas must perish, emigrate, or find ways to
      adjust to a suite of new selective pressures. Those that successfully inhabit the
      urban environment may make behavioral, physiological, and/or morphological
      adjustments that represent either evolutionary change and/or phenotypic
      plasticity. We tested for effects of urbanization on antipredator behavior and
      associated morphology across an urban-wild gradient in the western fence lizard
      (Sceloporus occidentalis) in two California counties, Santa Barbara and San Luis
      Obispo. We compared college campuses in both counties with adjacent rural
      habitats, conducting field trials that allowed us to characterize antipredator
      behavior in response to the acute stress of capture. We found notable divergence
      between campus and rural behavior, with campus lizards more frequently exhibiting
      diminished escape behavior, including tonic immobility, and lower sprint speeds.
      Furthermore, campus females had significantly shorter limbs, and while this did
      not explain variation in sprint speed, those with shorter limbs were more likely
      to show tonic immobility. We hypothesize that these parallel behavioral and
      morphological changes on both campuses reflect adjustment to a novel environment
      involving changes in predation and human presence.

PMID- 29444103
TI  - Macro and micro plastics sorb and desorb metals and act as a point source of
      trace metals to coastal ecosystems.
AB  - Nine urban intertidal regions in Burrard Inlet, Vancouver, British Columbia,
      Canada, were sampled for plastic debris. Debris included macro and micro plastics
      and originated from a wide diversity of uses ranging from personal hygiene to
      solar cells. Debris was characterized for its polymer through standard
      physiochemical characteristics, then subject to a weak acid extraction to remove
      the metals, zinc, copper, cadmium and lead from the polymer. Recently
      manufactured low density polyethylene (LDPE), nylon, polyethylene terephthalate
      (PET), polypropylene (PP), polystyrene (PS) and polyvinyl chloride (PVC) were
      subject to the same extraction. Data was statistically analyzed by appropriate
      parametric and non-parametric tests when needed with significance set at P <
      0.05. Polymers identified in field samples in order of abundance were; PVC (39),
      LDPE (28), PS (18), polyethylene (PE, 9), PP (8), nylon (8), high density
      polyethylene (HDPE, 7), polycarbonate (PC, 6), PET (6), polyurethane (PUR, 3) and
      polyoxymethylene (POM, 2). PVC and LDPE accounted for 46% of all samples. Field
      samples of PVC, HDPE and LDPE had significantly greater amounts of acid extracted
      copper and HDPE, LDPE and PUR significantly greater amounts of acid extracted
      zinc. PVC and LDPE had significantly greater amounts of acid extracted cadmium
      and PVC tended to have greater levels of acid extracted lead, significantly so
      for HDPE. Five of the collected items demonstrated extreme levels of acid
      extracted metal; greatest concentrations were 188, 6667, 698,000 and 930 MUgg-1
      of copper, zinc, lead and cadmium respectively recovered from an unidentified
      object comprised of PVC. Comparison of recently manufactured versus field samples
      indicated that recently manufactured samples had significantly greater amounts of
      acid extracted cadmium and zinc and field samples significantly greater amounts
      of acid extracted copper and lead which was primarily attributed to metal
      extracted from field samples of PVC. Plastic debris will affect metals within
      coastal ecosystems by; 1) providing a sorption site (copper and lead), notably
      for PVC 2) desorption from the plastic i.e., the "inherent" load (cadmium and
      zinc) and 3) serving as a point source of acute trace metal exposure to coastal
      ecosystems. All three mechanisms will put coastal ecosystems at risk to the toxic
      effects of these metals.

PMID- 29444104
TI  - ShDcR3 sensitizes TRAIL-resistant HCC cells by inducing caspase-dependent
      apoptosis while suppressing NF-kappaB dependent cFLIPL expression.
AB  - Evidence has shown that most hepatocellular carcinoma (HCC) cells are resistant
      to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated
      apoptosis. However, the molecular mechanisms underlying TRAIL-mediated apoptosis
      resistance are not well understood. In this study, we reported that
      downregulation of Decoy receptor 3 (DcR3) expression by lentiviral vectors
      carrying shRNA against DcR3 (LV-ShDcR3, shDcR3) in Huh7 both greatly enhanced
      TRAIL-mediated apoptosis and reduced cell proliferation capability. In addition,
      silencing DcR3 resulted in upregulation of the cell apoptotic regulators
      including Bid, caspase-3, and caspase-8. Caspase inhibitors inhibited shDcR3
      mediated cell death, which indicated that downregulation of DcR3 expression in
      Huh7 cells increased TRAIL-induced caspase-dependent apoptotic cell death.
      Furthermore, although the knockdown of DcR3 altered the expression of some Bcl-2-
      and IAP-family proteins, this change was inhibited by pretreatment with a
      pancaspase inhibitor, which indicated the cytotoxic effect of shDcR3 was not due
      to the expression of these proteins. In contrast, shDcR3 significantly inhibited
      TRAIL-induced transcription factor nuclear kappaB (NF-kappaB) activation through
      the IkappaB kinase (IKK) pathway, as well as inhibited TRAIL-induced increases in
      FLICE-inhibitory protein long form (cFLIPL) expression at the transcriptional
      level. Silencing cFLIPL expression mimicked the cytotoxic effect of shDcR3 on
      TRAIL-mediated cell apoptosis. Moreover, overexpression of cFLIPL effectively
      prevented the increase in cell apoptosis in Huh7 cells co-treated with TRAIL and
      shDcR3. Taken together, our findings indicated that silencing DcR3 sensitizes
      TRAIL-mediated apoptosis in HCC cells by inhibiting NF-kappaB.

PMID- 29444105
TI  - Accuracy and precision of consumer-level activity monitors for stroke detection
      during wheelchair propulsion and arm ergometry.
AB  - The purpose of this study was to evaluate whether consumer-level activity
      trackers can estimate wheelchair strokes and arm ergometer revolutions. Thirty
      able-bodied participants wore three consumer-level activity trackers (Garmin
      VivoFit, FitBit Flex, and Jawbone UP24) on the wrist. Participants propelled a
      wheelchair at fixed frequencies (30, 45 and 60 strokes per minute (spm)) three
      minutes each and at pre-determined varied frequencies, (30-80 spm) for two
      minutes. Participants also freely wheeled through an obstacle course. 10 other
      participants performed arm-ergometry at 40, 60 and 80 revolutions per minute
      (rpm), for three minutes each. Mean percentage error (MPE(SD)) for 30 spm were
      >=46(26)% for all monitors, and declined to 3-6(2-7)% at 60 spm. For the obstacle
      course, MPE ranged from 12-17(7-13)% for all trackers. For arm-ergometry, MPE was
      at 1-96(0-37)% with the best measurement for the Fitbit at 60 and 80 rpm, and the
      Garmin at 80rpm, with MPE = 1(0-1)%. The consumer-level wrist-worn activity
      trackers we tested have higher accuracy/precision at higher movement frequencies
      but perform poorly at lower frequencies.

PMID- 29444106
TI  - Prevalence and risk factors of strabismus in children and adolescents in South
      Korea: Korea National Health and Nutrition Examination Survey, 2008-2011.
AB  - PURPOSE: To evaluate the prevalence and risk factors associated with horizontal
      strabismus in children and adolescents in South Korea. METHODS: A total of 5,935
      children and adolescents 5-18 years of age who participated in the fourth and
      fifth Korean National Health and Nutrition Examination Survey (KNHANES IV-V) from
      July 2008 to December 2011 were evaluated and the prevalence of horizontal
      strabismus was estimated. Univariate and multivariate logistic regression
      analyses were conducted to determine the association between demographic,
      socioeconomic and clinical risk factors and clinically significant exodeviation
      (>=15 prism diopters [PD]) and esodeviation (>=10 PD). RESULTS: Among 5,935
      eligible subjects, 84 subjects had clinically significant exodeviation and 13 had
      clinically significant esodeviation. The overall prevalence of clinically
      significant horizontal strabismus was 1.6% (95% confidence interval [CI], 1.2
      2.1): 1.3% (95% CI, 1.0-1.7) for clinically significant exodeviation and 0.3%
      (95% CI, 0.1-0.6) for clinically significant esodeviation. Clinically significant
      exodeviation was associated with amblyopia (adjusted odds ratio [aOR], 6.45; 95%
      CI, 2.14-19.44), family history of strabismus (aOR, 4.91; 95% CI, 1.71-14.08) and
      astigmatism >=1.0 D (aOR, 1.84; 95% CI, 1.13-2.98). Clinically significant
      esodeviation was associated with hyperopia (aOR, 12.16; 95% CI, 1.31-113.04) and
      amblyopia (aOR, 4.70; 95% CI, 1.12-19.81). Other demographic, socioeconomic, and
      clinical variables were not associated with strabismus. CONCLUSION: This study
      provides data on the prevalence and independent risk factors for clinically
      significant exodeviation and esodeviation in a representative population of
      children and adolescents in South Korea.

PMID- 29444107
TI  - Shame in decision making under risk conditions: Understanding the effect of
      transparency.
AB  - The role played by the emotion of shame in the area of decision-making in
      situations of risk has hardly been studied. In this article, we show how the
      socio-moral emotions and the anticipated feeling of shame associated with
      different options can determine our decisions, even overriding the cognitive
      choice tendency proposed by the certainty effect. To do so, we carried out an
      experiment with university students as participants, dividing them into four
      experimental conditions. Our findings suggest that people avoid making unethical
      decisions, both when these decisions are made public to others and when they
      remain in the private sphere. This result seems to indicate that the main factor
      in not making unethical decisions is related to the need to avoid transgressing
      an internal moral standard of behavior, and that the role of transparency is less
      relevant than expected. However, we propose that, although the effect of
      transparency is limited in reducing unethical economic decisions, it should
      continue to be taken into account in theoretical models that address the reasons
      people behave unethically.

PMID- 29444109
TI  - Population structure of the NPGS Senegalese sorghum collection and its evaluation
      to identify new disease resistant genes.
AB  - Sorghum germplasm from West and Central Africa is cultivated in rainy and high
      humidity regions and is an important source of resistance genes to fungal
      diseases. Mold and anthracnose are two important biotic constraints to sorghum
      production in wet areas worldwide. Here, 158 National Plant Germplasm System
      (NPGS) accessions from Senegal were evaluated for agronomic traits, anthracnose,
      and grain mold resistance at two locations, and genetically characterized
      according to 20 simple sequence repeat markers. A total of 221 alleles were
      amplified with an average of 11 alleles per locus. Each accession had a unique
      genetic profile (i.e., no duplicates), and the average genetic distance between
      accessions was 0.42. Population structure and cluster analysis separated the
      collection into four populations with pairwise FST values >0.15. Three of the
      populations were composed of Guinea-race sorghum germplasm, and one included
      multiple races. Anthracnose resistant accessions were present at high frequency
      and evenly distributed among the three Guinea-race populations. Fourteen
      accessions showed resistance to grain mold, and eight were resistant to both
      diseases. These results indicated that the NPGS of Senegal is a genetically
      diverse collection with a high frequency of disease resistant accessions.
      Nevertheless, its population structure suggests the presence of few sources of
      resistance to both grain mold and anthracnose, which are fixed in the germplasm.
      The phenotypic and genotypic information for these accessions provides a valuable
      resource for its correct use to broaden the genetic base of breeding programs.

PMID- 29444108
TI  - Distribution of siderophore gene systems on a Vibrionaceae phylogeny: Database
      searches, phylogenetic analyses and evolutionary perspectives.
AB  - Siderophores are small molecules synthesized and secreted by bacteria and fungi
      to scavenge iron. Extracellular ferri-siderohores are recognized by cognate
      receptors on the cell surface for transport over membranes. Several siderophore
      systems from Vibrionaceae representatives are known and well understood, e.g.,
      the molecular structure of the siderophore, the biosynthesis gene cluster and
      pathway, and the gene expression pattern. Less is known about how these systems
      are distributed among the ~140 Vibrionaceae species, and which evolutionary
      processes contributed to the present-day distribution. In this work, we compiled
      existing knowledge on siderophore biosynthesis systems and siderophore receptors
      from Vibrionaceae and used phylogenetic analyses to investigate their
      organization, distribution, origin and evolution. Through literature searches, we
      identified nine different siderophore biosynthesis systems and thirteen
      siderophore receptors in Vibrionaceae. Homologs were identified by BLAST
      searches, and the results were mapped onto a Vibrionaceae phylogeny. We
      identified 81 biosynthetic systems distributed in 45 Vibrionaceae species and 16
      unclassified Vibrionaceae strains, and 409 receptors in 89 Vibrionaceae species
      and 49 unclassified Vibrionaceae strains. The majority of taxa are associated
      with at least one type of siderophore biosynthesis system, some (e.g., aerobactin
      and vibrioferrin) of which are widely distributed in the family, whereas others
      (i.e., bisucaberin and vibriobactin) are found in one lineage. Cognate receptors
      are found more widespread. Phylogenetic analysis of three siderophore systems
      (piscibactin, vibrioferrin and aerobactin) show that their present-day
      distribution can be explained by an old insertion into Vibrionaceae, followed
      mainly by stable vertical evolution and extensive loss, and some cases of
      horizontal gene transfers. The present work provides an up to date overview of
      the distribution of siderophore-based iron acquisition systems in Vibrionaceae,
      and presents phylogenetic analysis of these systems. Our results suggest that the
      present-day distribution is a result of several evolutionary processes, such as
      old and new gene acquisitions, gene loss, and both vertical and horizontal gene
      transfers.

PMID- 29444110
TI  - Leukemia inhibitory factor produced by fibroblasts within tumor stroma
      participates in invasion of oral squamous cell carcinoma.
AB  - The interaction between cancer cells and the cancer stroma plays a crucial role
      in tumor progression and metastasis in diverse malignancies, including oral
      cancer. However, the mechanism underlying this interaction remains incompletely
      elucidated. Here, to investigate the interaction between oral cancer cells and
      fibroblasts, which are major cellular components of the tumor stroma, we
      conducted an in vitro study by using human oral squamous cell carcinoma (OSCC)
      cell lines and normal human dermal fibroblasts (NHDFs). The results of transwell
      assays revealed that the migration and invasion of 2 OSCC cell lines, HO1-N-1 and
      HSC3, were markedly stimulated upon coculturing with NHDFs. To investigate the
      factors that promote tumor invasion, we isolated NHDFs from cocultures prepared
      with HO1-N-1 cells and performed microarray analysis. Among the various genes
      that were upregulated, we identified the gene encoding leukemia inhibitory factor
      (LIF), and we focused on LIF in further analyses. We confirmed that all OSCC
      derived conditioned media potently upregulated LIF expression in NHDFs, and the
      results of our transwell analysis demonstrated that NHDF-induced OSCC migration
      and invasion were inhibited by LIF-neutralizing antibodies. Furthermore,
      immunohistochemical analysis of patient samples revealed that in 44 out of 112
      OSCC cases, LIF was expressed in the tumor stroma, particularly in cancer
      associated fibroblasts (CAFs), and, notably, clinicopathological analyses
      confirmed that LIF expression in CAFs was significantly correlated with increased
      depth of tumor invasion. Collectively, our results suggest that OSCC stimulates
      fibroblasts to produce LIF, which, in turn, participates in cancer-cell invasion.
      Our finding offers a potential therapeutic strategy targeting the cancer stroma
      for the treatment of OSCC patients.

PMID- 29444111
TI  - Genome-wide identification and role of MKK and MPK gene families in clubroot
      resistance of Brassica rapa.
AB  - Mitogen-activated protein kinase (MAPK or MPK) cascades play key roles in
      responses to various biotic stresses, as well as in plant growth and development.
      However, the responses of MPK and MPK kinase (MKK) in Chinese cabbage (Brassica
      rapa ssp. pekinensis) to Plasmodiophora brassicae, a causal agent of clubroot
      disease in Brassica crops, are still not clear. In the present study, a total of
      11 B. rapa MKK (BraMKK) and 30 BraMPK genes were identified and unevenly
      distributed in 6 and 10 chromosomes, respectively. The synteny analysis indicated
      that these genes experienced whole-genome triplication and segmental and tandem
      duplication during or after the divergence of B. rapa, accompanied by the loss of
      three MKK and two MPK orthologs of Arabidopsis. The BraMKK and BraMPK genes were
      classified into four groups with similar intron/exon structures and conserved
      motifs in each group. A quantitative PCR analysis showed that the majority of
      BraMKK and BraMPK genes were natively expressed in roots, hypocotyls, and leaves,
      whereas 5 BraMKK and 16 BraMPK genes up-regulated in the roots upon P. brassicae
      infection. Additionally, these 5 BraMKK and 16 BraMPK genes exhibited a
      significantly different expression pattern between a pair of clubroot
      resistant/susceptible near-isogenic lines (NILs). Furthermore, the possible
      modules of MKK-MPK involved in B. rapa-P. brassicae interaction are also
      discussed. The present study will provide functional clues for further
      characterization of the MAPK cascades in B. rapa.

PMID- 29444112
TI  - Social network and dominance hierarchy analyses at Chimpanzee Sanctuary
      Northwest.
AB  - Different aspects of sociality bear considerable weight on the individual- and
      group-level welfare of captive nonhuman primates. Social Network Analysis (SNA)
      is a useful tool for gaining a holistic understanding of the dynamic social
      relationships of captive primate groups. Gaining a greater understanding of
      captive chimpanzees through investigations of centrality, preferred and avoided
      relationships, dominance hierarchy, and social network diagrams can be useful in
      advising current management practices in sanctuaries and other captive settings.
      In this study, we investigated the dyadic social relationships, group-level
      social networks, and dominance hierarchy of seven chimpanzees (Pan troglodytes)
      at Chimpanzee Sanctuary Northwest. We used focal-animal and instantaneous scan
      sampling to collect 106.75 total hours of associative, affiliative, and agonistic
      data from June to September 2016. We analyzed our data using SOCPROG to derive
      dominance hierarchies and network statistics, and we diagrammed the group's
      social networks in NetDraw. Three individuals were most central in the grooming
      network, while two others had little connection. Through agonistic networks, we
      found that group members reciprocally exhibited agonism, and the group's
      dominance hierarchy was statistically non-linear. One chimpanzee emerged as the
      most dominant through agonism but was least connected to other group members
      across affiliative networks. Our results indicate that the conventional methods
      used to calculate individuals' dominance rank may be inadequate to wholly depict
      a group's social relationships in captive sanctuary populations. Our results have
      an applied component that can aid sanctuary staff in a variety of ways to best
      ensure the improvement of group welfare.

PMID- 29444113
TI  - Effects of protein-protein interactions and ligand binding on the ion permeation
      in KCNQ1 potassium channel.
AB  - The voltage-gated KCNQ1 potassium ion channel interacts with the type I
      transmembrane protein minK (KCNE1) to generate the slow delayed rectifier (IKs)
      current in the heart. Mutations in these transmembrane proteins have been linked
      with several heart-related issues, including long QT syndromes (LQTS), congenital
      atrial fibrillation, and short QT syndrome. Off-target interactions of several
      drugs with that of KCNQ1/KCNE1 ion channel complex have been known to cause fatal
      cardiac irregularities. Thus, KCNQ1/KCNE1 remains an important avenue for drug
      design and discovery research. In this work, we present the structural and
      mechanistic details of potassium ion permeation through an open KCNQ1 structural
      model using the combined molecular dynamics and steered molecular dynamics
      simulations. We discuss the processes and key residues involved in the permeation
      of a potassium ion through the KCNQ1 ion channel, and how the ion permeation is
      affected by (i) the KCNQ1-KCNE1 interactions and (ii) the binding of chromanol
      293B ligand and its derivatives into the complex. The results reveal that
      interactions between KCNQ1 with KCNE1 causes a pore constriction in the former,
      which in-turn forms small energetic barriers in the ion-permeation pathway. These
      findings correlate with the previous experimental reports that interactions of
      KCNE1 dramatically slows the activation of KCNQ1. Upon ligand-binding onto the
      complex, the energy-barriers along ion permeation path are more pronounced, as
      expected, therefore, requiring higher force in our steered-MD simulations.
      Nevertheless, pulling the ion when a weak blocker is bound to the channel does
      not necessitate high force in SMD. This indicates that our SMD simulations have
      been able to discern between strong and week blockers and reveal their influence
      on potassium ion permeation. The findings presented here will have some
      implications in understanding the potential off-target interactions of the drugs
      with the KCNQ1/KCNE1 channel that lead to cardiotoxic effects.

PMID- 29444114
TI  - Childhood obesity treatment; Effects on BMI SDS, body composition, and fasting
      plasma lipid concentrations.
AB  - OBJECTIVE: The body mass index (BMI) standard deviation score (SDS) may not
      adequately reflect changes in fat mass during childhood obesity treatment. This
      study aimed to investigate associations between BMI SDS, body composition, and
      fasting plasma lipid concentrations at baseline and during childhood obesity
      treatment. METHODS: 876 children and adolescents (498 girls) with
      overweight/obesity, median age 11.2 years (range 1.6-21.7), and median BMI SDS
      2.8 (range 1.3-5.7) were enrolled in a multidisciplinary outpatient treatment
      program and followed for a median of 1.8 years (range 0.4-7.4). Height and
      weight, body composition measured by dual-energy X-ray absorptiometry, and
      fasting plasma lipid concentrations were assessed at baseline and at follow-up.
      Lipid concentrations (total cholesterol (TC), low-density lipoprotein (LDL), high
      density lipoprotein (HDL), non-HDL, and triglycerides (TG)) were available in 469
      individuals (264 girls). Linear regressions were performed to investigate the
      associations between BMI SDS, body composition indices, and lipid concentrations.
      RESULTS: At baseline, BMI SDS was negatively associated with concentrations of
      HDL (p = 6.7*10-4) and positively with TG (p = 9.7*10-6). Reductions in BMI SDS
      were associated with reductions in total body fat percentage (p<2*10-16) and
      percent truncal body fat (p<2*10-16). Furthermore, reductions in BMI SDS were
      associated with improvements in concentrations of TC, LDL, HDL, non-HDL, LDL/HDL
      ratio, and TG (all p <0.0001). Changes in body fat percentage seemed to mediate
      the changes in plasma concentrations of TC, LDL, and non-HDL, but could not alone
      explain the changes in HDL, LDL/HDL-ratio or TG. Among 81 individuals with
      available lipid concentrations, who increased their BMI SDS, 61% improved their
      body composition, and 80% improved their lipid concentrations. CONCLUSION:
      Reductions in the degree of obesity during multidisciplinary childhood obesity
      treatment are accompanied by improvements in body composition and fasting plasma
      lipid concentrations. Even in individuals increasing their BMI SDS, body
      composition and lipid concentrations may improve.

PMID- 29444115
TI  - Forest bat population dynamics over 14 years at a climate refuge: Effects of
      timber harvesting and weather extremes.
AB  - Long-term data are needed to explore the interaction of weather extremes with
      habitat alteration; in particular, can 'refugia' buffer population dynamics
      against climate change and are they robust to disturbances such as timber
      harvesting. Because forest bats are good indicators of ecosystem health, we used
      14 years (1999-2012) of mark-recapture data from a suite of small tree-hollow
      roosting bats to estimate survival, abundance and body condition in harvested and
      unharvested forest and over extreme El Nino and La Nina weather events in
      southeastern Australia. Trapping was replicated within an experimental forest,
      located in a climate refuge, with different timber harvesting treatments. We
      trapped foraging bats and banded 3043 with a 32% retrap rate. Mark-recapture
      analyses allowed for dependence of survival on time, species, sex, logging
      treatment and for transients. A large portion of the population remained
      resident, with a maximum time to recapture of nine years. The effect of logging
      history (unlogged vs 16-30 years post-logging regrowth) on apparent survival was
      minor and species specific, with no detectable effect for two species, a positive
      effect for one and negative for the other. There was no effect of logging history
      on abundance or body condition for any of these species. Apparent survival of
      residents was not strongly influenced by weather variation (except for the
      smallest species), unlike previous studies outside of refugia. Despite annual
      variation in abundance and body condition across the 14 years of the study, no
      relationship with extreme weather was evident. The location of our study area in
      a climate refuge potentially buffered bat population dynamics from extreme
      weather. These results support the value of climate refugia in mitigating climate
      change impacts, though the lack of an external control highlights the need for
      further studies on the functioning of climate refugia. Relatively stable
      population dynamics were not compromised by timber harvesting, suggesting
      ecologically sustainable harvesting may be compatible with climate refugia.

PMID- 29444116
TI  - Field evaluation of the safety, acceptability, and feasibility of early infant
      male circumcision using the AccuCirc device.
AB  - BACKGROUND: As countries scale up adult voluntary medical male circumcision
      (VMMC) for HIV prevention, they are looking ahead to long term sustainable
      strategies, including introduction of early infant male circumcision (EIMC).
      Although a number of devices for EIMC are prequalified by the World Health
      Organization, evaluation of additional devices can provide policy-makers and
      clinicians the information required to make informed decisions. We undertook a
      field evaluation of the safety and acceptability of the AccuCirc device in Kisumu
      County, Kenya. METHODS: Procedures were performed by four trained clinicians in
      two public facilities. Participants were recruited from surrounding public health
      facilities through informational talks at antenatal clinics, maternity wards, and
      maternal neonatal child health clinics. Healthy infants ages 0-60 days, with no
      penile abnormality, without a family history of bleeding disorder, with current
      weight-for-age within -2 Z-scores of WHO growth standards, and whose mother was
      at least 16 years of age were eligible for EIMC. The procedure was performed
      after administration of a penile dorsal nerve block using 2% lidocaine and
      administration of Vitamin K. The mother was given post-operative instructions on
      wound care and asked to remain in the clinic with the baby for an observational
      period of one hour, during which a face-to-face questionnaire was administered.
      RESULTS: Of 1259 babies screened, 704 were enrolled and circumcised. Median age
      of the infants was 16 days (IQR: 7-32.5) and of the mothers was 26 years (IQR: 22
      30). Median time for the procedure was 19 minutes (IQR: 15-23). There were no
      serious adverse events (AE), and 20 (2.8%) moderate AEs, all of which were due to
      bleeding that required application of one to three sutures. There were 22 (3.8%)
      procedures in which the device did not fully incise the entire circumference of
      the foreskin and had to be completed using sterile scissors. 89.9% of mothers had
      knowledge of EIMC, but few (8.1%) had any knowledge of devices used for EIMC.
      Protection against HIV/AIDS was the most cited reason to circumcise a baby
      (65.3%), while the baby being ill (38.1%) and pain (34.4%) were the most cited
      barriers to uptake. 99% of mothers were "very satisfied" or "completely
      satisfied" with the procedure. CONCLUSIONS: This evaluation of the AccuCirc
      device is the largest to date and indicates that the device is safe and
      acceptable, achieving high levels of parental satisfaction. The AccuCirc device
      should be considered for WHO prequalification to increase options for safe and
      sustainable provision of EIMC.

PMID- 29444118
TI  - Demographic and genetic viability of a medium-sized ground-dwelling mammal in a
      fire prone, rapidly urbanizing landscape.
AB  - The rapid and large-scale urbanization of peri-urban areas poses major and
      complex challenges for wildlife conservation. We used population viability
      analysis (PVA) to evaluate the influence of urban encroachment, fire, and fauna
      crossing structures, with and without accounting for inbreeding effects, on the
      metapopulation viability of a medium-sized ground-dwelling mammal, the southern
      brown bandicoot (Isoodon obesulus), in the rapidly expanding city of Perth,
      Australia. We surveyed two metapopulations over one and a half years, and
      parameterized the PVA models using largely field-collected data. The models
      revealed that spatial isolation imposed by housing and road encroachment has
      major impacts on I. obesulus. Although the species is known to persist in small
      metapopulations at moderate levels of habitat fragmentation, the models indicate
      that these populations become highly vulnerable to demographic decline, genetic
      deterioration, and local extinction under increasing habitat connectivity loss.
      Isolated metapopulations were also predicted to be highly sensitive to fire, with
      large-scale fires having greater negative impacts on population abundance than
      small-scale ones. To reduce the risk of decline and local extirpation of I.
      obesulus and other small- to medium-sized ground-dwelling mammals in urbanizing,
      fire prone landscapes, we recommend that remnant vegetation and vegetated,
      structurally-complex corridors between habitat patches be retained. Well-designed
      road underpasses can be effective to connect habitat patches and reduce the
      probability of inbreeding and genetic differentiation; however, adjustment of
      fire management practices to limit the size of unplanned fires and ensure the
      retention of long unburnt vegetation will also be required to ensure persistence.
      Our study supports the evidence that in rapidly urbanizing landscapes, a pro
      active conservation approach is required that manages species at the
      metapopulation level and that prioritizes metapopulations and habitat with
      greater long-term probability of persistence and conservation capacity,
      respectively. This strategy may help us prevent future declines and local
      extirpations, and currently relatively common species from becoming rare.

PMID- 29444117
TI  - An ancestral TMEM16 homolog from Dictyostelium discoideum forms a scramblase.
AB  - TMEM16 proteins are a recently identified protein family comprising Ca2+
      activated Cl- channels that generate outwardly rectifying ionic currents in
      response to intracellular Ca2+ elevations. Some TMEM16 family members, such as
      TMEM16F/ANO6 are also essential for Ca2+-dependent phospholipid scrambling.
      TMEM16-like genes are present in the genomes of most eukaryotic species, the
      function(s) of TMEM16 family members from evolutionary ancient eukaryotes is not
      completely clear. Here, we provide insight into the evolution of these TMEM16
      proteins by similarity searches for ancestral sequences. All eukaryotic genomes
      contain TMEM16 homologs, but only vertebrates have the full repertoire of ten
      distinct subtypes. TMEM16 homologs studied so far belong to the opisthokont
      branch of the phylogenetic tree, which includes the animal and fungal kingdoms.
      An organism outside this group is Dictyostelium discoideum, a representative of
      the amoebozoa group that diverged from the metazoa before fungi. We here
      functionally investigated the TMEM16 family member from Dictyostelium discoideum.
      When recombinantly expressed in HEK293 cells, DdTMEM16 induces phospholipid
      scrambling. However, in several electrophysiological experiments we did not find
      evidence for a Ca2+-activated Cl- channel function of DdTMEM16.

PMID- 29444119
TI  - Accurate and fast path computation on large urban road networks: A general
      approach.
AB  - Accurate and fast path computation is essential for applications such as onboard
      navigation systems and traffic network routing. While a number of heuristic
      algorithms have been developed in the past few years for faster path queries, the
      accuracy of them are always far below satisfying. In this paper, we first develop
      an agglomerative graph partitioning method for generating high balanced traverse
      distance partitions, and we constitute a three-level graph model based on the
      graph partition scheme for structuring the urban road network. Then, we propose a
      new hierarchical path computation algorithm, which benefits from the hierarchical
      graph model and utilizes a region pruning strategy to significantly reduce the
      search space without compromising the accuracy. Finally, we present a detailed
      experimental evaluation on the real urban road network of New York City, and the
      experimental results demonstrate the effectiveness of the proposed approach to
      generate optimal fast paths and to facilitate real-time routing applications.

PMID- 29444120
TI  - Computer tomography-based body surface area evaluation for drug dosage:
      Quantitative radiology versus anthropomorphic evaluation.
AB  - OBJECTIVE: The measure of body surface area (BSA) is a standard for planning
      optimal dosing in oncology. This index is derived from a model having
      questionable performances. In this study, we proposed measurement of BSA from
      whole body CT images (iBSA). We tested the reliability of iBSA assessments and
      simulated the impact of our approach on patient chemotherapy dosage planning.
      METHODS: We first evaluated accuracy and precision of iBSA in measuring 14
      phantom and 11 CT test-retest images.Secondly, we retrospectively analyzed 26
      whole body PET-CT scans to evaluate inter-method variability between iBSA and the
      most used anthropomorphic models, notably the "Du Bois and Du Bois" model.
      Finally, we simulated the impact on chemotherapy dose planning of capecitabine
      based on iBSA. RESULTS: Precision and accuracy of iBSA measurement featured a
      standard deviation of 1.11% and a mean error of 1.53%. Inter-method variability
      between iBSA and "Du Bois and Du Bois" assessment featured a standard deviation
      of 4.11% leading to a reclassification rate of capecitabine of 32.5%.
      CONCLUSIONS: iBSA could help the oncologist in standardizing assessments for
      chemotherapy planning. iBSA could also be relevant for applications such as
      comprehensive body composition and provide a sensitive measurement for changes
      related to nutritional intake or other metabolism.

PMID- 29444121
TI  - No evidence of a causal relationship between hypothyroidism and glaucoma: A
      Danish nationwide register-based cohort study.
AB  - BACKGROUND: An interrelationship between hypothyroidism and glaucoma, due to a
      shared autoimmune background or based on deposition of mucopolysaccharides in the
      trabecular meshwork in the eye, has been suggested but is at present
      unsubstantiated. Therefore, our objective was to investigate, at a nationwide and
      population-based level, whether there is such an association. SUBJECTS AND
      METHODS: Observational cohort study using record-linkage data from nationwide
      Danish health registers. 121,799 individuals diagnosed with a first episode of
      hypothyroidism were identified and were matched with 4 non-hypothyroid controls
      according to age and sex. Prevalence of glaucoma was recorded and cases and
      controls were followed over a mean of 7.1 years (range 0-17). Logistic and Cox
      regression models were used to assess the risk of glaucoma before and after the
      diagnosis of hypothyroidism, respectively. RESULTS: Overall, we found a higher
      prevalence of glaucoma in subjects with hypothyroidism as compared to controls
      (4.6% vs. 4.3%, p < 0.001). Prior to the diagnosis of hypothyroidism, the odds
      ratio (OR) was significantly increased for glaucoma [1.09; 95% confidence
      interval (CI): 1.04-1.13]. Based on the Cox regression model, there was no
      increased risk of glaucoma after the diagnosis of hypothyroidism [hazard ratio
      (HR) 1.00; 95% CI: 0.96-1.06], and the HR decreased further after adjusting for
      pre-existing co-morbidity (0.88; 95% CI: 0.84-0.93). CONCLUSIONS: There was an
      increased risk of glaucoma before but not after the diagnosis of hypothyroidism,
      suggesting that screening for glaucoma in hypothyroid individuals is unwarranted.

PMID- 29444122
TI  - Latent tuberculosis infection in foreign-born communities: Import vs.
      transmission in The Netherlands derived through mathematical modelling.
AB  - While tuberculosis (TB) represents a significant disease burden worldwide, low
      incidence countries strive to reach the WHO target of pre-elimination by 2035.
      Screening for TB in immigrants is an important component of the strategy to
      reduce the TB burden in low-incidence settings. An important option is the
      screening and preventive treatment of latent TB infection (LTBI). Whether this
      policy is worthwhile depends on the extent of transmission within the country,
      and introduction of new cases through import. Mathematical transmission models of
      TB have been used to identify key parameters in the epidemiology of TB and
      estimate transmission rates. An important application has also been to
      investigate the consequences of policy scenarios. Here, we formulate a
      mathematical model for TB transmission within the Netherlands to estimate the
      size of the pool of latent infections, and to determine the share of importation
      either through immigration or travel- versus transmission within the Netherlands.
      We take into account importation of infections due to immigration, and travel to
      the country of origin, focusing on the three ethnicities most represented among
      foreign-born TB cases (after exclusion of those overrepresented among asylum
      seekers): Moroccans, Turkish and Indonesians. We fit a system of ordinary
      differential equations to the data from the Netherlands Tuberculosis Registry on
      (extra-)pulmonary TB cases from 1995-2013. We estimate that about 27% of
      Moroccans, 25% of Indonesians, and 16% of Turkish, are latently infected.
      Furthermore, we find that for all three foreign-born communities, immigration is
      the most important source of LTBI, but the extent of within-country transmission
      is much lower (about half) for the Turkish and Indonesian communities than for
      the Moroccan. This would imply that contact investigation would have a greater
      yield in the latter community than in the former. Travel remains a minor factor
      contributing LTBI, suggesting that targeting returning travelers might be less
      effective at preventing LTBI than immigrants upon entry in the country.

PMID- 29444123
TI  - Survival from alcoholic hepatitis has not improved over time.
AB  - PURPOSE/BACKGROUND: We aimed to describe changes in survival in alcoholic
      hepatitis (AH) over time by examining published data. METHODS: A systematic
      literature search of Ovid Embase and PubMed was undertaken using the MESH terms
      'hepatitis, alcoholic' to identify randomised controlled trials (RCT) and
      observational studies (OS) in alcoholic hepatitis. Data were extracted from
      included studies regarding 28-day, 90-day, 180-day mortality, as well as
      biochemical and clinical data. RESULTS: After review of the literature search
      results, 77 studies published between 1971 and 2016 were analysed, which included
      data from a total of 8,184 patients. Overall mortality from AH was 26% at 28
      days, 29% at 90 days and 44% at 180 days after admission. No changes in mortality
      over time were observed in univariable analysis at 28 days or 90 days after
      admission (Pearson correlation r -0.216, p = 0.098, and r 0.121 p = 0.503
      respectively). A small but statistically significant increase in mortality was
      seen in 180-day mortality (r 0.461 p = 0.036). However, after meta-regression to
      adjust for other factors associated with mortality at each time point, no changes
      in mortality were seen. Sub-group analysis did not reveal any changes in
      mortality over time in different study types, or when only biopsy-proven or
      severe disease were considered. CONCLUSION: There has been no improvement in
      mortality from AH. This is not explained by changes in severity of disease. This
      emphasises the urgent need for effective treatments for this alcoholic hepatitis.

PMID- 29444124
TI  - Annual changes in rotavirus hospitalization rates before and after rotavirus
      vaccine implementation in the United States.
AB  - BACKGROUND: Hospitalizations for rotavirus and acute gastroenteritis (AGE) have
      declined in the US with rotavirus vaccination, though biennial peaks in incidence
      in children aged less than 5 years occur. This pattern may be explained by lower
      rotavirus vaccination coverage in US children (59% to 73% from 2010-2015),
      resulting in accumulation of susceptible children over two successive birth
      cohorts. METHODS: Retrospective cohort analysis of claims data of commercially
      insured US children aged <5 years. Age-stratified hospitalization rates for
      rotavirus and for AGE from the 2002-2015 rotavirus seasons were examined. Median
      age and rotavirus vaccination coverage for biennial rotavirus seasons during pre
      vaccine (2002-2005), early post-vaccine (2008-2011) and late post-vaccine (2012
      2015) years. RESULTS: Age-stratified hospitalization rates decreased from pre
      vaccine to early post-vaccine and then to late post-vaccine years. The clearest
      biennial pattern in hospitalization rates is the early post-vaccine period, with
      higher rates in 2009 and 2011 than in 2008 and 2010. The pattern diminishes in
      the late post-vaccine period. For rotavirus hospitalizations, the median age and
      the difference in age between biennial seasons was highest during the early post
      vaccine period; these differences were not observed for AGE hospitalizations.
      There was no significant difference in vaccination coverage between biennial
      seasons. CONCLUSIONS: These observations provide conflicting evidence that
      incomplete vaccine coverage drove the biennial pattern in rotavirus
      hospitalizations that has emerged with rotavirus vaccination in the US. As this
      pattern is diminishing with higher vaccine coverage in recent years, further
      increases in vaccine coverage may reach a threshold that eliminates peak seasons
      in hospitalizations.

PMID- 29444125
TI  - Exploration of avocado by-products as natural sources of bioactive compounds.
AB  - This study aimed to evaluate the antioxidant, anti-inflammatory, and cytotoxic
      properties and phenolic composition of peel and seed of avocado varieties Hass
      and Fuerte using green solvents. Ethanol soluble compounds were identified in
      peel and seed of both varieties using HPLC-MS/MS and quantified using HPLC-DAD.
      Agro-industrial by-products of both varieties exhibited high radical scavenging
      activity against synthetic free radicals (DPPH and ABTS) and reactive oxygen
      species (peroxyl, superoxide, and hypochlorous acid) and high ability to reduce
      Fe3+ to Fe2+. The main compounds with significant contribution to the antioxidant
      activity determined by online HPLC-ABTS?+ analyses were procyanidin B2 and
      epicatechin in the peel and trans-5-O-caffeoyl-D-quinic acid, procyanidin B1,
      catechin, and epicatechin in the seed. Peel of Fuerte significantly suppressed
      TNF-alpha and nitric oxide (NO) release (459.3 pg/mL and 8.5 MUM, respectively),
      possibly because of the high phenolic content and antioxidant activity detected.
      Avocado agro-industrial by-products can be used for food and pharmaceutical
      purposes due to their antioxidant and anti-inflammatory properties.

PMID- 29444126
TI  - Applying the multi-threat framework of stereotype threat in the context of
      digital gaming.
AB  - Females often report experiencing stigmatisation pertaining to their competency
      in digital gaming communities. Employing the principles of the multi-threat
      framework of stereotype threat, the current research examined the impact of
      gender-related stereotypes on females' gaming performance and related self
      perceptions. In Experiment 1, 90 females were assigned to one of three conditions
      in which they were primed that their performance would be either diagnostic of
      their personal (self-as-target) or gender group's ability (group-as-target) or
      would be non-diagnostic of gaming ability (control). In Experiment 2, 90 females
      were primed that their performance would be judged by a group of other females
      (in-group source) or males (out-group source), or would be non-diagnostic of
      ability (control). Participants then completed a casual gaming task, as well as
      measures of competence beliefs, self-efficacy and self-esteem. Findings from
      Experiment 1 indicate that neither a self-as-target nor a group-as-target
      stereotype affected significantly gaming performance, or game-related self
      efficacy, self-esteem and competency beliefs. Findings from Experiment 2 reveal
      further that females' gaming performance and associated self-perceptions were not
      impacted significantly by an in-group or out-group source of stereotype threat.
      The discussion turns to potential explanations for these findings, proposing that
      females may not perceive negative gender-gaming stereotypes to be an accurate
      representation of their personal or social group's gaming ability. We also
      discuss the implications of the experimental design and difficulty, as well as
      the potential for domain identification to moderate performance outcomes under
      stereotype threat.

PMID- 29444127
TI  - Reducing vertices in property graphs.
AB  - Graph databases are constantly growing, and, at the same time, some of their data
      is the same or similar. Our experience with the management of the existing
      databases, especially the bigger ones, shows that certain vertices are
      particularly replicated there numerous times. Eliminating repetitive or even very
      similar data speeds up the access to database resources. We present a
      modification of this approach, where similarly we group together vertices of
      identical properties, but then additionally we join together groups of data that
      are located in distant parts of a graph. The second part of our approach is non
      trivial. We show that the search for a partition of a given graph where each
      member of the partition has only pairwise distant vertices is NP-hard. We
      indicate a group of heuristics that try to solve our difficult computational
      problems and then we apply them to check the the effectiveness of our approach.

PMID- 29444128
TI  - Molecular action of isoflavone genistein in the human epithelial cell line HaCaT.
AB  - Due to its strong proliferation-reducing effects on keratinocytes, and also anti
      inflammatory properties, the isoflavone genistein has already been proposed as a
      possible antipsoriatic compound. As there is still no detailed information on
      this topic, we examined the effects of genistein by using an in vitro model of
      both, normal and "psoriasis-like" keratinocytes at this stage of our work
      exhaustively testing the selected flavonoid in a mono-treated experimental
      design. Gene expression studies revealed transcriptional changes that confirms
      known disease-associated pathways and highlights many psoriasis-related genes.
      Our results suggested that aberrant expression of genes contributing to the
      progress of psoriasis could be improved by the action of genistein. Genistein
      prevented "cytokine mix" as well as TNF-alpha-induced NF-kappaB nuclear
      translocation, with no effect on the PI3K signaling cascade, indicating the luck
      of turning this pathway into NF-kappaB activation. It could have attenuated TNF
      alpha and LPS-induced inflammatory responses by suppressing ROS activation.
      Regardless of the type of keratinocyte stimulation used, reduction of cytokine IL
      8, IL-20 and CCL2 production (both at RNA and protein level) following genistein
      treatment was visible. Because investigations of other groups supported our
      commentary on potential administration of genistein as a potential weapon in the
      armamentarium against psoriasis, it is believed that this paper should serve to
      encourage researchers to conduct further studies on this subject.

PMID- 29444129
TI  - Long-term habitat changes in a protected area: Implications for herpetofauna
      habitat management and restoration.
AB  - Point Pelee National Park, located at the southern-most tip of Canada's mainland,
      historically supported a large number of herpetofauna species; however, despite
      nearly a century of protection, six snake and five amphibian species have
      disappeared, and remaining species-at-risk populations are thought to be in
      decline. We hypothesized that long-term changes in availability and distribution
      of critical habitat types may have contributed to the disappearance of
      herpetofauna. To track habitat changes we used aerial image data spanning 85
      years (1931-2015) and manually digitized and classified image data using a
      standardized framework. Change-detection analyses were used to evaluate the
      relative importance of proportionate loss and fragmentation of 17 habitat types.
      Marsh habitat diversity and aquatic connectivity has declined since 1931. The
      marsh matrix transitioned from a graminoid and forb shallow marsh interspersed
      with water to a cattail dominated marsh, altering critical breeding, foraging,
      and overwintering habitat. Reduced diversity of marsh habitats appears to be
      linked to the expansion of invasive Phragmites australis, which invaded prior to
      2000. Loss of open habitats such as savanna and meadow has reduced availability
      of high quality thermoregulation habitat for reptiles. Restoration of the
      northwestern region and tip of Point Pelee National Park to a mixed landscape of
      shallow wetlands (cattail, graminoid, forb, open water) and eradication of dense
      Phragmites stands should improve habitat diversity. Our results suggest that long
      term landscape changes resulting from habitat succession and invasive species can
      negatively affect habitat suitability for herpetofauna and protection of land
      alone does not necessarily equate to protection of sensitive herpetofauna.

PMID- 29444130
TI  - "Are you gonna publish that?" Peer-reviewed publication outcomes of doctoral
      dissertations in psychology.
AB  - If a doctoral dissertation represents an original investigation that makes a
      contribution to one's field, then dissertation research could, and arguably
      should, be disseminated into the scientific literature. However, the extent and
      nature of dissertation publication remains largely unknown within psychology. The
      present study investigated the peer-reviewed publication outcomes of psychology
      dissertation research in the United States. Additionally, we examined publication
      lag, scientific impact, and variations across subfields. To investigate these
      questions, we first drew a stratified random cohort sample of 910 psychology
      Ph.D. dissertations from ProQuest Dissertations & Theses. Next, we conducted
      comprehensive literature searches for peer-reviewed journal articles derived from
      these dissertations published 0-7 years thereafter. Published dissertation
      articles were coded for their bibliographic details, citation rates, and journal
      impact metrics. Results showed that only one-quarter (25.6% [95% CI: 23.0, 28.4])
      of dissertations were ultimately published in peer-reviewed journals, with
      significant variations across subfields (range: 10.1 to 59.4%). Rates of
      dissertation publication were lower in professional/applied subfields (e.g.,
      clinical, counseling) compared to research/academic subfields (e.g.,
      experimental, cognitive). When dissertations were published, however, they often
      appeared in influential journals (e.g., Thomson Reuters Impact Factor M = 2.84
      [2.45, 3.23], 5-year Impact Factor M = 3.49 [3.07, 3.90]) and were cited numerous
      times (Web of Science citations per year M = 3.65 [2.88, 4.42]). Publication
      typically occurred within 2-3 years after the dissertation year. Overall, these
      results indicate that the large majority of Ph.D. dissertation research in
      psychology does not get disseminated into the peer-reviewed literature. The non
      publication of dissertation research appears to be a systemic problem affecting
      both research and training in psychology. Efforts to improve the quality and
      "publishability" of doctoral dissertation research could benefit psychological
      science on multiple fronts.

PMID- 29444131
TI  - Chromatin immunoprecipitation improvements for the processing of small frozen
      pieces of adipose tissue.
AB  - Chromatin immunoprecipitation (ChIP) has gained importance to identify links
      between the genome and the proteome. Adipose tissue has emerged as an active
      tissue, which secretes a wide range of molecules that have been related to
      metabolic and obesity-related disorders, such as diabetes, cardiovascular
      failure, metabolic syndrome, or cancer. In turn, epigenetics has raised the
      importance in discerning the possible relationship between metabolic disorders,
      lifestyle and environment. However, ChIP application in human adipose tissue is
      limited by several factors, such as sample size, frozen sample availability, high
      lipid content and cellular composition of the tissue. Here, we optimize the
      standard protocol of ChIP for small pieces of frozen human adipose tissue. In
      addition, we test ChIP for the histone mark H3K4m3, which is related to active
      promoters, and validate the performance of the ChIP by analyzing gene promoters
      for factors usually studied in adipose tissue using qPCR. Our improvements result
      in a higher performance in chromatin shearing and DNA recovery of adipocytes from
      the tissue, which may be useful for ChIP-qPCR or ChIP-seq analysis.

PMID- 29444132
TI  - A linear bi-level multi-objective program for optimal allocation of water
      resources.
AB  - This paper presents a simple bi-level multi-objective linear program (BLMOLP)
      with a hierarchical structure consisting of reservoir managers and several water
      use sectors under a multi-objective framework for the optimal allocation of
      limited water resources. Being the upper level decision makers (i.e., leader) in
      the hierarchy, the reservoir managers control the water allocation system and
      tend to create a balance among the competing water users thereby maximizing the
      total benefits to the society. On the other hand, the competing water use
      sectors, being the lower level decision makers (i.e., followers) in the
      hierarchy, aim only to maximize individual sectoral benefits. This multi
      objective bi-level optimization problem can be solved using the simultaneous
      compromise constraint (SICCON) technique which creates a compromise between upper
      and lower level decision makers (DMs), and transforms the multi-objective
      function into a single decision-making problem. The bi-level model developed in
      this study has been applied to the Swat River basin in Pakistan for the optimal
      allocation of water resources among competing water demand sectors and different
      scenarios have been developed. The application of the model in this study shows
      that the SICCON is a simple, applicable and feasible approach to solve the BLMOLP
      problem. Finally, the comparisons of the model results show that the optimization
      model is practical and efficient when it is applied to different conditions with
      priorities assigned to various water users.

PMID- 29444133
TI  - A long-term mechanistic computational model of physiological factors driving the
      onset of type 2 diabetes in an individual.
AB  - A computational model of the physiological mechanisms driving an individual's
      health towards onset of type 2 diabetes (T2D) is described, calibrated and
      validated using data from the Diabetes Prevention Program (DPP). The objective of
      this model is to quantify the factors that can be used for prevention of T2D. The
      model is energy and mass balanced and continuously simulates trajectories of
      variables including body weight components, fasting plasma glucose, insulin, and
      glycosylated hemoglobin among others on the time-scale of years. Modeled
      mechanisms include dynamic representations of intracellular insulin resistance,
      pancreatic beta-cell insulin production, oxidation of macronutrients,
      ketogenesis, effects of inflammation and reactive oxygen species, and conversion
      between stored and activated metabolic species, with body-weight connected to
      mass and energy balance. The model was calibrated to 331 placebo and 315
      lifestyle-intervention DPP subjects, and one year forecasts of all individuals
      were generated. Predicted population mean errors were less than or of the same
      magnitude as clinical measurement error; mean forecast errors for weight and
      HbA1c were ~5%, supporting predictive capabilities of the model. Validation of
      lifestyle-intervention prediction is demonstrated by synthetically imposing diet
      and physical activity changes on DPP placebo subjects. Using subject level
      parameters, comparisons were made between exogenous and endogenous
      characteristics of subjects who progressed toward T2D (HbA1c > 6.5) over the
      course of the DPP study to those who did not. The comparison revealed significant
      differences in diets and pancreatic sensitivity to hyperglycemia but not in
      propensity to develop insulin resistance. A computational experiment was
      performed to explore relative contributions of exogenous versus endogenous
      factors between these groups. Translational uses to applications in public health
      and personalized healthcare are discussed.

PMID- 29444134
TI  - Effect of antibiotic withdrawal in feed on chicken gut microbial dynamics,
      immunity, growth performance and prevalence of foodborne pathogens.
AB  - Development of antibiotic resistance in foodborne pathogens, Salmonella spp. and
      Campylobacter, is a public health concern. Public demand to reduce the use of sub
      therapeutic antibiotic growth promoters (AGP) in poultry feeding has resulted in
      greater adoption of antibiotic-free poultry production systems. There is a need
      to understand the effects of AGP removal from poultry feed on gut microbiota and
      its impact on prevalence of foodborne pathogens. The effect of antibiotic
      withdrawal from poultry feed on gut microbial community, host performance and
      immunity, and prevalence of Salmonella and Campylobacter was evaluated. Birds
      were raised on three phase diets (starter [d0-22], grower [d23-35] and finisher
      [d36-42]) with and without bacitracin dimethyl salicyclate (BMD). At early growth
      stage, bird performance was improved (P <= 0.05) with BMD treatment, whereas
      performance was better (P <= 0.05) in control group (no BMD in the feed) at the
      time of commercial processing. Acetate and butyrate production was affected (P <=
      0.05) by age, whereas propionate production was affected (P <= 0.05) by both the
      treatment and age. The bacterial communities in the cecum were more diverse (P <=
      0.001) and rich compared to the ileal communities, and they shifted in parallel
      to one another as the chicks matured. Differences in diversity and species
      richness were not observed (P > 0.05) between the BMD-fed and control groups.
      Comparing all ages, treatments and diets, the composition of cecal and ileal
      bacterial communities was different (P <= 0.001). Inclusion of BMD in the feed
      did not affect the bacterial phyla. However, predictable shift in the ileal and
      cecal bacterial population at lower taxonomic level was observed in control vs
      BMD-fed group. Cytokines gene expression (IL-10, IL-4, IFN-gamma, beta-defensin,
      and TLR-4) was affected (P<= 0.05) in the BMD-fed group at early stages of
      growth. The prevalence of foodborne pathogens, Campylobacter spp. and Salmonella
      spp. showed higher abundance in the ilea of BMD-fed chicks compared to control
      group. Overall, this study provided insight of the impact of AGP supplementation
      in the feed on gut microbial modulations, bird performance, host immunity and
      pathogen prevalence. This information can assist in designing alternative
      strategies to replace antibiotics in modern poultry production and for food
      safety.

PMID- 29444135
TI  - Diagnosis of amphimeriasis by LAMPhimerus assay in human stool samples long-term
      storage onto filter paper.
AB  - Amphimeriasis, a fish-borne zoonotic disease caused by the liver fluke Amphimerus
      spp., has recently been reported as an emerging disease affecting an indigenous
      Ameridian group, the Chachi, living in Ecuador. The only method for diagnosing
      amphimeriasis was the microscopic detection of eggs from the parasite in
      patients' stool samples with very low sensitivity. Our group developed an ELISA
      technique for detection of anti-Amphimerus IgG in human sera and a molecular
      method based on LAMP technology (named LAMPhimerus) for specific and sensitive
      parasite DNA detection. The LAMPhimerus method showed to be much more sensitive
      than classical parasitological methods for amphimeriasis diagnosis using human
      stool samples for analysis. The objective of this work is to demonstrate the
      feasibility of using dried stool samples on filter paper as source of DNA in
      combination with the effectiveness of our previously designed LAMPhimerus assay
      for successfully Amphimerus sp. detection in clinical stool samples. A total of
      102 untreated and undiluted stool samples collected from Chachi population were
      spread as thin layer onto common filter paper for easily transportation to our
      laboratory and stored at room temperature for one year until DNA extraction. When
      LAMPhimerus method was applied for Amphimerus sp. DNA detection, a higher number
      of positive results was detected (61/102; 59.80%) in comparison to
      parasitological methods (38/102; 37.25%), including 28/61 (45.90%) microscopy
      confirmed Amphimerus sp. infections. The diagnostic parameters for the
      sensitivity and specificity werecalculated for our LAMPhimerus assay, which were
      79.17% and 65.98%, respectively. We demonstrate, for the first time, that common
      filter paper is useful for easy collection and long-term storage of human stool
      samples for later DNA extraction and molecular analysis of human-parasitic
      trematode eggs. This simple, economic and easily handling method combined with
      the specific and sensible LAMPhimerus assay has the potential to beused as an
      effective molecular large-scale screening test for amphimeriasis-endemic areas.

PMID- 29444136
TI  - LY2405319, an analog of fibroblast growth factor 21 ameliorates alpha-smooth
      muscle actin production through inhibition of the succinate-G-protein couple
      receptor 91 (GPR91) pathway in mice.
AB  - Fibroblast growth factor 21 (FGF21) is an important metabolic regulator expressed
      predominantly in the liver. In this study, we evaluated the role of LY2405319, an
      analogue of FGF21, in hepatic stellate cell (HSC) activation and in a methionine
      and choline-deficient (MCD)-diet induced mouse model of liver fibrosis. During
      liver injury, HSCs trans-differentiate into activated myofibroblasts which
      produce alpha-smooth muscle actin (alpha-SMA) and become a major cell type in
      hepatic fibrogenesis. Succinate and succinate receptor (GPR91) signaling has
      emerged as a regulator to promote alpha-SMA production in MCD diet- induced mice.
      Treatment with palmitate or MCD medium on LX-2 cells (HSCs) increased succinate
      concentration in the conditioned medium and cell lysate of LX-2 cells and
      increased production of GPR91 and alpha-SMA. However, LY2405319 administration
      ameliorates palmitate or MCD media-induced succinate production and decreases
      over-expression of GPR91 and alpha-SMA in LX2-cells. In an in vivo study, the MCD
      diet treatment caused increased steatohepatitis and liver fibrosis compared with
      the control diet in mice. Administration of LY2405319 improved steatohepatitis
      ameliorated GPR91 and alpha -SMA production in the liver, decreased succinate
      concentration in both liver and serum of MCD diet -induced mice. These results
      suggest that FGF21 reduces production of alpha-SMA by inhibiting the succinate
      GPR91 pathway. We conclude that FGF21 acts as an inhibitor of the succinate-GPR91
      pathway to control liver fibrosis. This suggests that FGF21 has therapeutic
      potential for treating liver fibrogenesis.

PMID- 29444137
TI  - Anxiety is not enough to drive me away: A latent profile analysis on math anxiety
      and math motivation.
AB  - Mathematics anxiety (MA) and mathematics motivation (MM) are important multi
      dimensional non-cognitive factors in mathematics learning. While the negative
      relation between global MA and MM is well replicated, the relations between
      specific dimensions of MA and MM are largely unexplored. The present study
      utilized latent profile analysis to explore profiles of various aspects of MA
      (including learning MA and exam MA) and MM (including importance, self-perceived
      ability, and interest), to provide a more holistic understanding of the math
      specific emotion and motivation experiences. In a sample of 927 high school
      students (13-21 years old), we found 8 distinct profiles characterized by various
      combinations of dimensions of MA and MM, revealing the complexity in the math
      specific emotion-motivation relation beyond a single negative correlation.
      Further, these profiles differed on mathematics learning behaviors and
      mathematics achievement. For example, the highest achieving students reported
      modest exam MA and high MM, whereas the most engaged students were characterized
      by a combination of high exam MA and high MM. These results call for the need to
      move beyond linear relations among global constructs to address the complexity in
      the emotion-motivation-cognition interplay in mathematics learning, and highlight
      the importance of customized intervention for these heterogeneous groups.

PMID- 29444138
TI  - Voxel level quantification of [11C]CURB, a radioligand for Fatty Acid Amide
      Hydrolase, using high resolution positron emission tomography.
AB  - [11C]CURB is a novel irreversible radioligand for imaging fatty acid amide
      hydrolase in the human brain. In the present work, we validate an algorithm for
      generating parametric map images of [11C]CURB acquired with a high resolution
      research tomograph (HRRT) scanner. This algorithm applies the basis function
      method on an irreversible two-tissue compartment model (k4 = 0) with arterial
      input function, i.e., BAFPIC. Monte Carlo simulations are employed to assess bias
      and variability of the binding macroparameters (Ki and lambdak3) as a function of
      the voxel noise level and the range of basis functions. The results show that for
      a [11C]CURB time activity curve with noise levels corresponding to a voxel of an
      image acquired with the HRRT and reconstructed with the filtered back projection
      algorithm, the implementation of BAFPIC requires the use of a constant vascular
      fraction of tissue (5%) and a cutoff for slow frequencies (0.06 min-1). With
      these settings, BAFPIC maintains the probabilistic distributions of the binding
      macroparameters with approximately Gaussian shape and minimizes the bias and
      variability for large physiological ranges of the rate constants of [11C]CURB.
      BAFPIC reduces the variability of Ki to a third of that given by Patlak plot, the
      standard graphical method for irreversible radioligands. Application to real data
      demonstrated an excellent correlation between region of interest and BAFPIC
      parametric data and agreed with the simulations results. Therefore, BAFPIC with a
      constant vascular fraction can be used to generate parametric maps of [11C]CURB
      images acquired with an HRRT provided that the limits of the basis functions are
      carefully selected.

PMID- 29444139
TI  - Post-discharge body weight and neurodevelopmental outcomes among very low birth
      weight infants in Taiwan: A nationwide cohort study.
AB  - BACKGROUND: Premature infants are at high risk for developmental delay and
      cognitive dysfunction. Besides medical conditions, growth restriction is regarded
      as an important risk factor for cognitive and neurodevelopmental dysfunction
      throughout childhood and adolescence and even into adulthood. In this study, we
      analyzed the relationship between post-discharge body weight and psychomotor
      development using a nationwide dataset. MATERIALS AND METHODS: This was a
      nationwide cohort study conducted in Taiwan. Total of 1791 premature infants born
      between 2007 and 2011 with a birth weight of less than 1500 g were enrolled into
      this multi-center study. The data were obtained from the Taiwan Premature Infant
      Developmental Collaborative Study Group. The growth and neurodevelopmental
      evaluations were performed at corrected ages of 6, 12 and 24 months. Post
      discharge failure to thrive was defined as a body weight below the 3rd percentile
      of the standard growth curve for Taiwanese children by the corrected age.
      RESULTS: The prevalence of failure to thrive was 15.8%, 16.9%, and 12.0% at
      corrected ages of 6, 12, and 24 months, respectively. At corrected ages of 24
      months, 12.9% had low Mental Developmental Index (MDI) scores (MDI<70), 17.8% had
      low Psychomotor Developmental Index (PDI) scores (PDI<70), 12.7% had cerebral
      palsy, and 29.5% had neurodevelopmental impairment. Post-discharge failure to
      thrive was significantly associated with poor neurodevelopmental outcomes. After
      controlling for potential confounding factors (small for gestational age, extra
      uterine growth retardation at discharge, cerebral palsy, gender, mild
      intraventricular hemorrhage, persistent pulmonary hypertension of newborn,
      respiratory distress syndrome, chronic lung disease, hemodynamic significant
      patent ductus arteriosus, necrotizing enterocolitis, surfactant use and
      indomethacin use), post-discharge failure to thrive remained a risk factor.
      CONCLUSION: This observational study observed the association between lower body
      weight at corrected age of 6, 12, and 24 months and poor neurodevelopmental
      outcomes among VLBW premature infants. There are many adverse factors which can
      influence the neurodevelopment in NICU care. More studies are needed to elucidate
      the causal relationship.

PMID- 29444140
TI  - Getting to FP2020: Harnessing the private sector to increase modern contraceptive
      access and choice in Ethiopia, Nigeria, and DRC.
AB  - BACKGROUND: An estimated 214 million women have unmet need for family planning in
      developing regions. Improved utilization of the private sector is key to
      achieving universal access to a range of safe and effective modern contraceptive
      methods stipulated by FP2020 and SDG commitments. Until now, a lack of market
      data has limited understanding of the private sector's role in increasing
      contraceptive coverage and choice. METHODS: In 2015, the FPwatch Project
      conducted representative outlet surveys in Ethiopia, Nigeria, and DRC using a
      full census approach in selected administrative areas. Every public and private
      sector outlet with the potential to sell or distribute modern contraceptives was
      approached. In outlets with modern contraceptives, product audits and provider
      interviews assessed contraceptive market composition, availability, and price.
      FINDINGS: Excluding general retailers, 96% of potential outlets in Ethiopia, 55%
      in Nigeria, and 41% in DRC had modern contraceptive methods available. In
      Ethiopia, 41% of modern contraceptive stocking outlets were in the private sector
      compared with approximately 80% in Nigeria and DRC where drug shops were
      dominant. Ninety-five percent of private sector outlets in Ethiopia had modern
      contraceptive methods available; 37% had three or more methods. In Nigeria and
      DRC, only 54% and 42% of private sector outlets stocked modern contraceptives
      with 5% and 4% stocking three or more methods, respectively. High prices in
      Nigeria and DRC create barriers to consumer access and choice. DISCUSSION: There
      is a missed opportunity to provide modern contraception through the private
      sector, particularly drug shops. Subsidies and interventions, like social
      marketing and social franchising, could leverage the private sector's role in
      increasing access to a range of contraceptives. Achieving global FP2020
      commitments depends on the expansion of national contraceptive policies that
      promote greater partnership and cooperation with the private sector and
      improvement of decisions around funding streams of countries with large
      populations and high unmet need like Ethiopia, Nigeria, and DRC.

PMID- 29444141
TI  - The 3-min all-out test is valid for determining critical power but not anaerobic
      work capacity in tethered running.
AB  - The purpose of the study was to investigate if the 3-min all-out test (3MT) is
      valid for obtaining critical power intensity (CP) and the amount of work that can
      be performed above CP (W') on non-motorized treadmills in tethered running. Eight
      physically active individuals (24 +/- 3 years; 78.3 +/- 8.7 kg; 179 +/- 5 cm; 9.0
      +/- 2.5% body fat) performed four different efforts at constant intensity to
      exhaustion in order to determine CP and W'. The mechanical power values obtained
      were subsequently plotted with their corresponding time to exhaustion (limit
      time) for application of three mathematical models: power hyperbolic versus time
      limit (Hyp), linear power versus 1/time (P vs 1/t) and linear work versus time
      limit (? vs t). The 3MT test was carried out on the last day to determine end
      power (EP) and anaerobic capacity (WEP) using this methodology. EP value of 181.7
      +/- 52 was similar (p = 0.486) to 178.2 +/- 61 (CP Hyp), 191.4 +/- 55 (? vs t)
      and 188.3 +/- 55 (P vs 1/t). WEP value of 17.9 +/- 4.8 was not similar (p =
      0.000) to 50.2 +/- 15.3 (CP Hyp), 44.8 +/- 8.7 (? vs t) and 45.5 +/- 8.4 (P vs
      1/t). Positive results (r = 0.78-0.98 and ICC = 0.88-0.99) of Pearson correlation
      and intraclass correlation (ICC-absolute agreement) were found for aerobic
      applications of conventional CP and 3MT. For anaerobic data, only the three
      models of conventional CP were correlated (r = 0.76-0.93); however, W' from the
      three models was not correlated with WEP (r = 0.37-0.52). The results of this
      study suggest that 3MT in tethered running on non-motorized treadmills is a valid
      test for estimating CP aerobic parameters in a single day of application but not
      anaerobic parameters of W'.

PMID- 29444142
TI  - Roots of symptom-free leguminous cover crop and living mulch species harbor
      diverse Fusarium communities that show highly variable aggressiveness on pea
      (Pisum sativum).
AB  - Leguminous cover crop and living mulch species show not only great potential for
      providing multiple beneficial services to agro-ecosystems, but may also present
      pathological risks for other crops in rotations through shared pathogens,
      especially those of the genus Fusarium. Disease severity on roots of subterranean
      clover, white clover, winter and summer vetch grown as cover crop and living
      mulch species across five European sites as well as the frequency, distribution
      and aggressiveness to pea of Fusarium spp. recovered from the roots were assessed
      in 2013 and 2014. Disease symptoms were very low at all sites. Nevertheless, out
      of 1480 asymptomatic roots, 670 isolates of 14 Fusarium spp. were recovered. The
      most frequently isolated species in both years from all hosts were F. oxysporum
      and F. avenaceum accounting for 69% of total isolation percentage. They were
      common at the Swiss, Italian and German sites, whereas at the Swedish site F.
      oxysporum dominated and F. avenaceum occurred only rarely. The agressiveness and
      effect on pea biomass were tested in greenhouse assays for 72 isolates of six
      Fusarium species. Isolates of F. avenaceum caused severe root rot symptoms with
      mean severity index (DI) of 82 and 74% mean biomass reduction compared to the non
      inoculated control. Fusarium oxysporum and F. solani isolates were higly variable
      in agressiveness and their impact on pea biomass. DI varied between 15 and 50 and
      biomass changes relative to the non-inoculated control -40% to +10%. Isolates of
      F. tricinctum, F. acuminatum and F. equiseti were non to weakly agressive often
      enhancing pea biomass. This study shows that some of the major pea pathogens are
      characterized by high ecological plasticity and have the ability to
      endophytically colonize the hosts studied that thus may serve as inoculum
      reservoir for susceptible main legume grain crops such as pea.

PMID- 29444144
TI  - Improved GGIW-PHD filter for maneuvering non-ellipsoidal extended targets or
      group targets tracking based on sub-random matrices.
AB  - For non-ellipsoidal extended targets and group targets tracking (NETT and NGTT),
      using an ellipsoid to approximate the target extension may not be accurate enough
      because of the lack of shape and orientation information. In consideration of
      this, we model a non-ellipsoidal extended target or target group as a combination
      of multiple ellipsoidal sub-objects, each represented by a random matrix. Based
      on these models, an improved gamma Gaussian inverse Wishart probability
      hypothesis density (GGIW-PHD) filter is proposed to estimate the measurement
      rates, kinematic states, and extension states of the sub-objects for each
      extended target or target group. For maneuvering NETT and NGTT, a multi-model
      (MM) approach based GGIW-PHD (MM-GGIW-PHD) filter is proposed. The common and the
      individual dynamics of the sub-objects belonging to the same extended target or
      target group are described by means of the combination between the overall
      maneuver model and the sub-object models. For the merging of updating components,
      an improved merging criterion and a new merging method are derived. A specific
      implementation of prediction partition with pseudo-likelihood method is
      presented. Two scenarios for non-maneuvering and maneuvering NETT and NGTT are
      simulated. The results demonstrate the effectiveness of the proposed algorithms.

PMID- 29444143
TI  - Australian shellfish ecosystems: Past distribution, current status and future
      direction.
AB  - We review the status of marine shellfish ecosystems formed primarily by bivalves
      in Australia, including: identifying ecosystem-forming species, assessing their
      historical and current extent, causes for decline and past and present
      management. Fourteen species of bivalves were identified as developing complex,
      three-dimensional reef or bed ecosystems in intertidal and subtidal areas across
      tropical, subtropical and temperate Australia. A dramatic decline in the extent
      and condition of Australia's two most common shellfish ecosystems, developed by
      Saccostrea glomerata and Ostrea angasi oysters, occurred during the mid-1800s to
      early 1900s in concurrence with extensive harvesting for food and lime
      production, ecosystem modification, disease outbreaks and a decline in water
      quality. Out of 118 historical locations containing O. angasi-developed
      ecosystems, only one location still contains the ecosystem whilst only six
      locations are known to still contain S. glomerata-developed ecosystems out of 60
      historical locations. Ecosystems developed by the introduced oyster Crasostrea
      gigas are likely to be increasing in extent, whilst data on the remaining 11
      ecosystem-forming species are limited, preventing a detailed assessment of their
      current ecosystem-forming status. Our analysis identifies that current knowledge
      on extent, physical characteristics, biodiversity and ecosystem services of
      Australian shellfish ecosystems is extremely limited. Despite the limited
      information on shellfish ecosystems, a number of restoration projects have
      recently been initiated across Australia and we propose a number of existing
      government policies and conservation mechanisms, if enacted, would readily serve
      to support the future conservation and recovery of Australia's shellfish
      ecosystems.

PMID- 29444145
TI  - Waggawagga-CLI: A command-line tool for predicting stable single alpha-helices
      (SAH-domains), and the SAH-domain distribution across eukaryotes.
AB  - Stable single-alpha helices (SAH-domains) function as rigid connectors and
      constant force springs between structural domains, and can provide contact
      surfaces for protein-protein and protein-RNA interactions. SAH-domains mainly
      consist of charged amino acids and are monomeric and stable in polar solutions,
      characteristics which distinguish them from coiled-coil domains and intrinsically
      disordered regions. Although the number of reported SAH-domains is steadily
      increasing, genome-wide analyses of SAH-domains in eukaryotic genomes are still
      missing. Here, we present Waggawagga-CLI, a command-line tool for predicting and
      analysing SAH-domains in protein sequence datasets. Using Waggawagga-CLI we
      predicted SAH-domains in 24 datasets from eukaryotes across the tree of life. SAH
      domains were predicted in 0.5 to 3.5% of the protein-coding content per species.
      SAH-domains are particularly present in longer proteins supporting their function
      as structural building block in multi-domain proteins. In human, SAH-domains are
      mainly used as alternative building blocks not being present in all transcripts
      of a gene. Gene ontology analysis showed that yeast proteins with SAH-domains are
      particular enriched in macromolecular complex subunit organization, cellular
      component biogenesis and RNA metabolic processes, and that they have a strong
      nuclear and ribonucleoprotein complex localization and function in ribosome and
      nucleic acid binding. Human proteins with SAH-domains have roles in all types of
      RNA processing and cytoskeleton organization, and are predicted to function in
      RNA binding, protein binding involved in cell and cell-cell adhesion, and
      cytoskeletal protein binding. Waggawagga-CLI allows the user to adjust the
      stabilizing and destabilizing contribution of amino acid interactions in i,i+3
      and i,i+4 spacings, and provides extensive flexibility for user-designed
      analyses.

PMID- 29444146
TI  - Prediction of small for size syndrome after extended hepatectomy: Tissue
      characterization by relaxometry, diffusion weighted magnetic resonance imaging
      and magnetization transfer.
AB  - This study aimed to monitor the course of liver regeneration by multiparametric
      magnetic-resonance imaging (MRI) after partial liver resection characterizing
      Small-for-Size Syndrome (SFSS), which frequently leads to fatal post-hepatectomy
      liver failure (PLF). Twenty-two C57BL/6 mice underwent either conventional 70%
      partial hepatectomy (cPH), extended 86% partial hepatectomy (ePH) or SHAM
      operation. Subsequent MRI scans on days 0, 1, 2, 3, 5 and 7 in a 4.7T MR Scanner
      quantified longitudinal and transverse relaxation times, apparent diffusion
      coefficient (ADC) and the magnetization-transfer ratio (MTR) of the regenerating
      liver parenchyma. Histological examination was performed by hematoxylin-eosin
      staining. After hepatectomy, an increase of T1 time was detected being larger for
      ePH on day 1: 18% for cPH vs. 40% for ePH and on day 2: 24% for cPH vs. 49% for
      ePH. An increase in T2 time, again greater in ePH was most pronounced on day 5:
      21% for cPH vs. 41% for ePH. ADC and MTR showed a decrease on day 1: 21% for ePH
      vs. 13% for cPH for ADC, 15% for ePH vs. 11% for cPH for MTR. Subsequently, all
      MR parameters converged towards initial values in surviving animals. Dying PLF
      animals exhibited the strongest increase of T1 relaxation time and most prominent
      decreases of ADC and MTR. The retrieved MRI biomarkers indicate SFSS and
      potentially developing PLF at an early stage, likely reflecting cellular
      hypertrophy with extended water content and concomitantly diluted cellular
      components as features of liver regeneration, appearing more intense in ePH as
      compared to cPH.

PMID- 29444147
TI  - Increasing influenza vaccination rates via low cost messaging interventions.
AB  - This article tests low cost interventions to increase influenza vaccination
      rates. By changing an email announcement sent out to employees in 2014 (n >
      30,000), the following interventions are tested: incentives, attention to the
      negative impacts of not get vaccinated, and showing a map to the vaccination
      centers at the end of the email announcement. Only the map condition helped
      increase influenza vaccination rates. The use of low-cost interventions can
      improve influenza vaccination rates though not all interventions work as well as
      others in the field. In particular, while including maps helped increase
      vaccination rates, other factors such as negative impact reminders and
      incentives, which previous studies have found to be successful in the laboratory,
      did not.

PMID- 29444149
TI  - Sociability between invasive guppies and native topminnows.
AB  - The role of interspecific social interactions during species invasions may be
      more decisive than previously thought. Research has revealed that invasive fish
      improve their foraging success by shoaling with native Mexican species, and
      potentially increase the chances of invasion success. However, do native
      individuals tend to associate with invaders as well? We tested the hypothesis
      that the twoline skiffia (Neotoca bilineata) and the Lerma livebearer
      (Poeciliopsis infans), both native endemic Mexican topminnows, will associate
      with guppies, a notorious invasive species present in Mexico. Our investigation
      shows that guppies, twoline skiffias and Lerma livebearers have a mutual tendency
      to associate with each other. Although there is a marked tendency to shoal with
      heterospecifics in this system, shoaling partners do not necessarily benefit
      equally from the association. Further research on invasive-native social
      interactions is needed to promote our understanding of potential facilitation by
      natives.

PMID- 29444148
TI  - Development of a recombinase polymerase amplification assay for rapid detection
      of Francisella noatunensis subsp. orientalis.
AB  - Francisella noatunensis subsp. orientalis (Fno) is the causative agent of piscine
      francisellosis in warm water fish including tilapia. The disease induces chronic
      granulomatous inflammation with high morbidity and can result in high mortality.
      Early and accurate detection of Fno is crucial to set appropriate outbreak
      control measures in tilapia farms. Laboratory detection of Fno mainly depends on
      bacterial culture and molecular techniques. Recombinase polymerase amplification
      (RPA) is a novel isothermal technology that has been widely used for the
      molecular diagnosis of various infectious diseases. In this study, a recombinase
      polymerase amplification (RPA) assay for rapid detection of Fno was developed and
      validated. The RPA reaction was performed at a constant temperature of 42 degrees
      C for 20 min. The RPA assay was performed using a quantitative plasmid standard
      containing a unique Fno gene sequence. Validation of the assay was performed not
      only by using DNA from Fno, closely related Francisella species and other common
      bacterial pathogens in tilapia farms, but also by screening 78 Nile tilapia and 5
      water samples. All results were compared with those obtained by previously
      established real-time qPCR. The developed RPA showed high specificity in
      detection of Fno with no cross-detection of either the closely related
      Francisella spp. or the other tested bacteria. The Fno-RPA performance was highly
      comparable to the published qPCR with detection limits at 15 and 11 DNA molecules
      detected, respectively. The RPA gave quicker results in approximately 6 min in
      contrast to the qPCR that needed about 90 min to reach the same detection limit,
      taking only 2.7-3 min to determine Fno in clinical samples. Moreover, RPA was
      more tolerant to reaction inhibitors than qPCR when tested with field samples.
      The fast reaction, simplicity, cost-effectiveness, sensitivity and specificity
      make the RPA an attractive diagnostic tool that will contribute to controlling
      the infection through prompt on-site detection of Fno.

PMID- 29444150
TI  - Probiotic and anti-inflammatory potential of Lactobacillus rhamnosus 4B15 and
      Lactobacillus gasseri 4M13 isolated from infant feces.
AB  - A total of 22 Lactobacillus strains, which were isolated from infant feces were
      evaluated for their probiotic potential along with resistance to low pH and bile
      salts. Eight isolates (L. reuteri 3M02 and 3M03, L. gasseri 4M13, 4R22, 5R01,
      5R02, and 5R13, and L. rhamnosus 4B15) with high tolerance to acid and bile
      salts, and ability to adhere to the intestine were screened from 22 strains.
      Further, functional properties of 8 Lactobacillus strains, such as anti
      oxidation, inhibition of alpha-glucosidase activity, cholesterol-lowering, and
      anti-inflammation were evaluated. The properties were strain-specific.
      Particularly, two strains of L. rhamnosus, 4B15 (4B15) and L. gasseri 4M13 (4M13)
      showed considerably higher anti-oxidation, inhibition of alpha-glucosidase
      activity, and cholesterol-lowering, and greater inhibition of nitric oxide
      production than other strains. Moreover, the two selected strains substantially
      inhibited the release of inflammatory mediators such as TNF-alpha, IL-6, IL
      1beta, and IL-10 stimulated the treatment of RAW 264.7 macrophages with LPS. In
      addition, whole genome sequencing and comparative genomic analysis of 4B15 and
      4M13 indicated them as novel genomic strains. These results suggested that 4B15
      and 4M13 showed the highest probiotic potential and have an impact on immune
      health by modulating pro-inflammatory cytokines.

PMID- 29444151
TI  - Predicting 1-year mortality after hospitalization for community-acquired
      pneumonia.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a major public health problem
      with high short- and long-term mortality. The main aim of this study was to
      develop and validate a specific prognostic index for one-year mortality in
      patients admitted for CAP. METHODS: This was an observational, prospective study
      of adults aged >=18 years admitted to Galdakao-Usansolo Hospital (Bizkaia, Spain)
      from January 2001 to July 2009 with a diagnosis of CAP surviving the first 15
      days. The entire cohort was divided into two parts, in order to develop a one
      year mortality predictive model in the derivation cohort, before validation using
      the second cohort. RESULTS: A total of 2351 patients were included and divided
      into a derivation and a validation cohort. After deaths within 15 days were
      excluded, one-year mortality was 10.63%. A predictive model was created in order
      to predict one-year mortality, with a weighted score that included: aged over 80
      years (4 points), congestive heart failure (2 points), dementia (6 points),
      respiratory rate >=30 breaths per minute (2 points) and blood urea nitrogen >30
      mg/dL (3 points) as predictors of higher risk with C-index of 0.76. This new
      model showed better predictive ability than current risk scores, PSI, CURB65 and
      SCAP with C-index of 0.73, 0.69 and 0.70, respectively. CONCLUSIONS: An easy-to
      use score, called the one-year CAPSI, may be useful for identifying patients with
      a high probability of dying after an episode of CAP.

PMID- 29444153
TI  - Head movements and postures as pain behavior.
AB  - Pain assessment can benefit from observation of pain behaviors, such as guarding
      or facial expression, and observational pain scales are widely used in clinical
      practice with nonverbal patients. However, little is known about head movements
      and postures in the context of pain. In this regard, we analyze videos of three
      publically available datasets. The BioVid dataset was recorded with healthy
      participants subjected to painful heat stimuli. In the BP4D dataset, healthy
      participants performed a cold-pressor test and several other tasks (meant to
      elicit emotion). The UNBC dataset videos show shoulder pain patients during range
      of-motion tests to their affected and unaffected limbs. In all videos,
      participants were sitting in an upright position. We studied head movements and
      postures that occurred during the painful and control trials by measuring head
      orientation from video over time, followed by analyzing posture and movement
      summary statistics and occurrence frequencies of typical postures and movements.
      We found significant differences between pain and control trials with analyses of
      variance and binomial tests. In BioVid and BP4D, pain was accompanied by head
      movements and postures that tend to be oriented downwards or towards the pain
      site. We also found differences in movement range and speed in all three
      datasets. The results suggest that head movements and postures should be
      considered for pain assessment and research. As additional pain indicators, they
      possibly might improve pain management whenever behavior is assessed, especially
      in nonverbal individuals such as infants or patients with dementia. However, in
      advance more research is needed to identify specific head movements and postures
      in pain patients.

PMID- 29444152
TI  - The interaction between cannabis use and the Val158Met polymorphism of the COMT
      gene in psychosis: A transdiagnostic meta - analysis.
AB  - BACKGROUND: Neither environmental nor genetic factors are sufficient to predict
      the transdiagnostic expression of psychosis. Therefore, analysis of gene
      environment interactions may be productive. OBJECTIVE: A meta-analysis was
      performed using papers investigating the interaction between cannabis use and
      catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). DATA
      SOURCES: PubMed, Embase, PsychInfo. STUDY ELIGIBILITY CRITERIA: All observational
      studies assessing the interaction between COMTVal158Met and cannabis with any
      psychosis or psychotic symptoms measure as an outcome. STUDY APPRAISAL AND
      SYNTHESIS METHODS: A meta-analysis was performed using the Meta-analysis of
      Observational Studies in Epidemiology guidelines and forest plots were generated.
      Thirteen articles met the selection criteria: 7 clinical studies using a case
      only design, 3 clinical studies with a dichotomous outcome, and 3 studies
      analysing a continuous outcome of psychotic symptoms below the threshold of
      psychotic disorder. The three study types were analysed separately. Validity of
      the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool:
      for Non-Randomized Studies of Interventions". RESULTS: For case-only studies, a
      significant interaction was found between cannabis use and COMTVal158Met, with an
      OR of 1.45 (95% Confidence Interval = 1.05-2.00; Met/Met as the risk genotype).
      However, there was no evidence for interaction in either the studies including
      dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the
      studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16
      0.08). LIMITATION: A substantial part of the included studies used the case-only
      design, which has lower validity and tends to overestimate true effects.
      CONCLUSION: The interaction term between cannabis use and COMTVal158Met was only
      statistically significant in the case-only studies, but not in studies using
      other clinical or non-clinical psychosis outcomes. Future additional high quality
      studies might change current perspectives, yet currently evidence for the
      interaction remains unconvincing.

PMID- 29444154
TI  - Associations between owner personality and psychological status and the
      prevalence of canine behavior problems.
AB  - Behavioral problems are a major source of poor welfare and premature mortality in
      companion dogs. Previous studies have demonstrated associations between owners'
      personality and psychological status and the prevalence and/or severity of their
      dogs' behavior problems. However, the mechanisms responsible for these
      associations are currently unknown. Other studies have detected links between the
      tendency of dogs to display behavior problems and their owners' use of aversive
      or confrontational training methods. This raises the possibility that the effects
      of owner personality and psychological status on dog behavior are mediated via
      their influence on the owner's choice of training methods. We investigated this
      hypothesis in a self-selected, convenience sample of 1564 current dog owners
      using an online battery of questionnaires designed to measure, respectively,
      owner personality, depression, emotion regulation, use of
      aversive/confrontational training methods, and owner-reported dog behavior.
      Multivariate linear and logistic regression analyses identified modest, positive
      associations between owners' use of aversive/confrontational training methods and
      the prevalence/severity of the following dog behavior problems: owner-directed
      aggression, stranger-directed aggression, separation problems, chasing,
      persistent barking, and house-soiling (urination and defecation when left alone).
      The regression models also detected modest associations between owners' low
      scores on four of the 'Big Five' personality dimensions (Agreeableness, Emotional
      Stability, Extraversion & Conscientiousness) and their dogs' tendency to display
      higher rates of owner-directed aggression, stranger-directed fear, and/or
      urination when left alone. The study found only weak evidence to support the
      hypothesis that these relationships between owner personality and dog behavior
      were mediated via the owners' use of punitive training methods, but it did detect
      a more than five-fold increase in the use of aversive/confrontational training
      techniques among men with moderate depression. Further research is needed to
      clarify the causal relationship between owner personality and psychological
      status and the behavioral problems of companion dogs.

PMID- 29444155
TI  - Conjunctival melanocytic naevus: Diagnostic value of anterior segment optical
      coherence tomography and ultrasound biomicroscopy.
AB  - PURPOSE: Conjunctival naevi are the most frequently diagnosed primary melanocytic
      lesions of the conjunctiva. The clinical manifestations are greatly variable
      which may result in diagnostic difficulties and differential diagnostic
      confusions. Therefore aims of the present study were: 1) to assess the
      morphologic features of conjunctival naevi; 2) to delineate the anterior segment
      optical coherence tomography (AS-OCT) characteristics of these lesions; 3) to
      compare AS-OCT and ultrasound biomicroscopy (UBM) as diagnostic tools in these
      alterations and 4) to correlate histological results with the AS-OCT pictures in
      case of surgically excised naevi. METHODS: All lesions were photo-documented. AS
      OCT and UBM (over the age of 18 years) were performed. Surgically excised lesions
      were admitted to histological examinations. RESULTS: In our series of 57
      conjunctival naevi, 54.4% were highly pigmented, 15.8% proved to be amelanotic.
      AS-OCT could detect intralesional cysts in 61.4% of the naevi, while slit-lamp
      and UBM proved to be less sensitive (40.3% vs. 28.5%). UBM could visualize the
      posterior margins of all naevi, while AS-OCT proved to be less sensitive with the
      detection of 89.4% of posterior naevus margins. Thickness of the conjunctival
      epithelial layer could be measured with AS-OCT in case of subepithelial naevi,
      while no distinct epithelial layer could be detected in compound and junctional
      naevi. CONCLUSIONS: Superiority of AS-OCT over UBM was demonstrated in
      visualizing internal structures of conjunctival naevi. UBM proved to be a better
      tool in highly pigmented and remarkably elevated naevi. Correlation was found
      between the histological type of the naevus and the thickness of the epithelial
      layer covering the lesion.

PMID- 29444156
TI  - Protein S-glutathionylation lowers superoxide/hydrogen peroxide release from
      skeletal muscle mitochondria through modification of complex I and inhibition of
      pyruvate uptake.
AB  - Protein S-glutathionylation is a reversible redox modification that regulates
      mitochondrial metabolism and reactive oxygen species (ROS) production in liver
      and cardiac tissue. However, whether or not it controls ROS release from skeletal
      muscle mitochondria has not been explored. In the present study, we examined if
      chemically-induced protein S-glutathionylation could alter superoxide (O2?
      )/hydrogen peroxide (H2O2) release from isolated muscle mitochondria. Disulfiram,
      a powerful chemical S-glutathionylation catalyst, was used to S-glutathionylate
      mitochondrial proteins and ascertain if it can alter ROS production. It was found
      that O2?-/H2O2 release rates from permeabilized muscle mitochondria decreased
      with increasing doses of disulfiram (100-500 MUM). This effect was highest in
      mitochondria oxidizing succinate or palmitoyl-carnitine, where a ~80-90% decrease
      in the rate of ROS release was observed. Similar effects were detected in intact
      mitochondria respiring under state 4 conditions. Incubation of disulfiram-treated
      mitochondria with DTT (2 mM) restored ROS release confirming that these effects
      were associated with protein S-glutathionylation. Disulfiram treatment also
      inhibited phosphorylating and proton leak-dependent respiration. Radiolabelled
      substrate uptake experiments demonstrated that disulfiram inhibited pyruvate
      import but had no effect on carnitine uptake. Immunoblot analysis of complex I
      revealed that it contained several protein S-glutathionylation targets including
      NDUSF1, a subunit required for NADH oxidation. Taken together, these results
      demonstrate that O2?-/H2O2 release from muscle mitochondria can be altered by
      protein S-glutathionylation. We attribute these changes to the protein S
      glutathionylation complex I and inhibition of mitochondrial pyruvate carrier.

PMID- 29444158
TI  - Practicable methods for histological section thickness measurement in
      quantitative stereological analyses.
AB  - The accuracy of quantitative stereological analysis tools such as the (physical)
      disector method substantially depends on the precise determination of the
      thickness of the analyzed histological sections. One conventional method for
      measurement of histological section thickness is to re-embed the section of
      interest vertically to its original section plane. The section thickness is then
      measured in a subsequently prepared histological section of this orthogonally re
      embedded sample. However, the orthogonal re-embedding (ORE) technique is quite
      work- and time-intensive and may produce inaccurate section thickness measurement
      values due to unintentional slightly oblique (non-orthogonal) positioning of the
      re-embedded sample-section. Here, an improved ORE method is presented, allowing
      for determination of the factual section plane angle of the re-embedded section,
      and correction of measured section thickness values for oblique (non-orthogonal)
      sectioning. For this, the analyzed section is mounted flat on a foil of known
      thickness (calibration foil) and both the section and the calibration foil are
      then vertically (re-)embedded. The section angle of the re-embedded section is
      then calculated from the deviation of the measured section thickness of the
      calibration foil and its factual thickness, using basic geometry. To find a
      practicable, fast, and accurate alternative to ORE, the suitability of spectral
      reflectance (SR) measurement for determination of plastic section thicknesses was
      evaluated. Using a commercially available optical reflectometer (F20,
      Filmetrics(r), USA), the thicknesses of 0.5 MUm thick semi-thin Epon (glycid
      ether)-sections and of 1-3 MUm thick plastic sections (glycolmethacrylate/
      methylmethacrylate, GMA/MMA), as regularly used in physical disector analyses,
      could precisely be measured within few seconds. Compared to the measured section
      thicknesses determined by ORE, SR measures displayed less than 1% deviation. Our
      results prove the applicability of SR to efficiently provide accurate section
      thickness measurements as a prerequisite for reliable estimates of dependent
      quantitative stereological parameters.

PMID- 29444157
TI  - Does radiation therapy increase gadolinium accumulation in the brain?:
      Quantitative analysis of T1 shortening using R1 relaxometry in glioblastoma
      multiforme patients.
AB  - OBJECTIVE: This study evaluated the possibility of accelerated gadolinium
      accumulation in irradiated brain parenchyma where the blood-brain barrier was
      weakened. METHODS: From January 2010 to June 2015, 44 patients with
      supratentorial glioblastoma were retrospectively identified who underwent pre-
      and post-radiation brain MR imaging, including R1 mapping. The mean dose of
      administered gadobutrol (Gadovist, Bayer, Germany) was 5.1 vials. Regions of
      interest (ROIs) were drawn around tumors that were located within 50-100% iso
      dose lines of maximum radiation dose. ROIs were also drawn at globus pallidus,
      thalamus, and cerebral white matter. Averages of R1 values (unit: s-1) before and
      after radiation and those of R1 ratio (post-radiation R1 / pre-radiation R1) were
      compared by t-test or rank sum test as appropriate. Multiple linear regression
      analysis was performed to evaluate independent association factors for R1 value
      increase at irradiated parenchyma. RESULTS: The mean R1 values in peri-tumoral
      areas were significantly increased after radiotherapy (0.7901+/-0.0977 [mean+/
      SD] vs. 0.8146+/-0.1064; P <.01). The mean R1 ratio of high radiation dose areas
      was significantly higher than that of low dose areas (1.0055+/-0.0654 vs.
      0.9882+/-0.0642; P <.01). The mean R1 ratio was lower in those who underwent
      hypofractionated radiotherapy (mean dose, 45.0 Gy) than those who underwent
      routine radiotherapy (mean dose, 61.1 Gy) (0.9913+/-0.0740 vs. 1.0463+/-0.0633; P
      = .08). Multiple linear regression analysis revealed that only radiotherapy type
      was significantly associated with increased R1 (P = .02) around tumors.
      CONCLUSIONS: Radiotherapy can induce R1 value increase in the brain parenchyma,
      which might suggest accelerated gadolinium accumulation due to damage to the
      blood-brain barrier.

PMID- 29444159
TI  - Antitumor effects of metformin via indirect inhibition of protein phosphatase 2A
      in patients with endometrial cancer.
AB  - OBJECTIVE: Metformin, an antidiabetic drug, inhibits the endometrial cancer cell
      growth in vivo by improving the insulin resistance; however, its mechanism of
      action is not completely understood. Protein phosphatase 2A (PP2A) is a
      serine/threonine phosphatase associated with insulin resistance and type 2
      diabetes, and its inhibition restores the insulin resistance. This study
      investigated the antitumor effect of metformin on endometrial cancer with a focus
      on PP2A. METHODS: Metformin (1,500-2,250 mg/day) was preoperatively administered
      to patients with endometrial cancer for 4 to 6 weeks. Expression of the PP2A
      regulatory subunits, 4 (PPP2R4) and B (PP2A-B), was evaluated using real-time
      polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) using paired
      specimens obtained before and after metformin treatment. The effect of PPP2R4
      inhibition with small interfering RNA was evaluated in the endometrial cancer
      cell lines HEC265 and HEC1B. P values of < .05 were considered statistically
      significant. RESULTS: Preoperative metformin treatment significantly reduced the
      expression of PP2A-B, as determined using IHC, and the mRNA expression of PPP2R4,
      as determined using RT-PCR, in the patients with endometrial cancer. However,
      metformin could not directly alter the PPP2R4 mRNA levels in the endometrial
      cancer cell lines in vitro. PPP2R4 knockdown reduced the proliferation and
      induced the apoptosis by activating caspases 3/7 in HEC265 and HEC1B cells.
      CONCLUSIONS: Downregulation of the PP2A-B subunit, including PPP2R4, is an
      important indirect target of metformin. Inhibition of PP2A may be an option for
      the treatment of endometrial cancer patients with insulin resistance. TRIAL
      REGISTRATION: This trial is registered with UMIN-CTR (number UMIN000004852).

PMID- 29444160
TI  - Towards the use of similarity distances to music genre classification: A
      comparative study.
AB  - Music genre classification is a challenging research concept, for which open
      questions remain regarding classification approach, music piece representation,
      distances between/within genres, and so on. In this paper an investigation on the
      classification of generated music pieces is performed, based on the idea that
      grouping close related known pieces in different sets -or clusters- and then
      generating in an automatic way a new song which is somehow "inspired" in each
      set, the new song would be more likely to be classified as belonging to the set
      which inspired it, based on the same distance used to separate the clusters.
      Different music pieces representations and distances among pieces are used;
      obtained results are promising, and indicate the appropriateness of the used
      approach even in a such a subjective area as music genre classification is.

PMID- 29444161
TI  - A 3D anatomical atlas of appendage musculature in the chelicerate arthropod
      Limulus polyphemus.
AB  - Limulus polyphemus, an archetypal chelicerate taxon, has interested both
      biological and paleontological researchers due to its unique suite of anatomical
      features and as a useful modern analogue for fossil arthropod groups. To assist
      the study and documentation of this iconic taxon, we present a 3D atlas on the
      appendage musculature, with specific focus on the muscles of the cephalothoracic
      appendages. As L. polyphemus appendage musculature has been the focus of
      extensive study, depicting the muscles in 3D will facilitate a more complete
      understanding thereof for future researchers. A large museum specimen was CT
      scanned to illustrate the major exoskeletal features of L. polyphemus. Micro-CT
      scans of iodine-stained appendages from fresh, non-museum specimens were
      digitally dissected to interactively depict appendage sections and muscles. This
      study has revealed the presence of two new muscles: one within the pushing leg,
      located dorsally relative to all other patella muscles, and the other within the
      male pedipalp, located in the modified tibiotarsus. This atlas increases
      accessibility to important internal and external morphological features of L.
      polyphemus and reduces the need for destructive fresh tissue dissection of
      specimens. Scanning, digitally dissecting, and documenting taxa in 3D is a
      pivotal step towards creating permanent digital records of life on Earth.

PMID- 29444162
TI  - Low serum levels of High-Density Lipoprotein cholesterol (HDL-c) as an indicator
      for the development of severe postpartum depressive symptoms.
AB  - Postpartum depression (PPD) is a psychiatric complication of childbirth affecting
      10-20% of new mothers and has negative impact on both mother and infant. Serum
      lipid levels have been related to depressive disorders, but very limited
      literatures are available regarding the lipid levels in women with postpartum
      depression. The present study is aimed to examine the association of serum lipids
      with the development of postpartum depressive symptoms. This is a cross sectional
      study conducted at a tertiary care hospital in South India. Women who came for
      postpartum check-up at 6th week post-delivery were screened for PPD (September
      2014-October 2015). Women with depressive symptoms were assessed using EPDS
      (Edinburgh Postnatal Depression Scale). The study involved 186 cases and 250
      controls matched for age and BMI. Serum levels of lipid parameters were estimated
      through spectrophotometry and the atherogenic indices were calculated in all the
      subjects. Low serum levels of Total Cholesterol (TC) and High Density Lipoprotein
      cholesterol (HDL-c) were significantly low in PPD women with severe depressive
      symptoms. The study recorded a significant negative correlation between HDL-c and
      the EPDS score in PPD women (r = -0.140, p = 0.05). Interestingly, the study also
      observed a significant negative correlation between Body Mass Index (BMI) and
      EPDS scores in case group (r = -0.146, p = 0.047), whereas a positive correlation
      between the same in controls (r = 0.187, p = 0.004). Our study demonstrated that
      low levels of serum HDL-c is correlated with the development of severe depressive
      symptoms in postpartum women. Study highlights the role of lipids in the
      development of postpartum depressive symptoms.

PMID- 29444163
TI  - The effect of "NutramilTM Complex," food for special medical purpose, on breast
      and prostate carcinoma cells.
AB  - NutramilTM Complex is a multicomponent food product that meets the requirements
      of a food for special medical purpose. As a complete, high-energy diet it
      consists of properly balanced nutrients, vitamins and minerals. The aim of this
      study was to assess the effect of NutramilTM Complex on breast and prostate
      carcinoma cells. Our results showed that NutramilTM Complex reduced the viability
      and proliferation of breast and prostate cancer cells and that this process was
      associated with the induction of apoptosis via activation of caspase signalling.
      Data showed elevated levels of p53 tumour suppressor, up-regulation of p38 MAPK
      and SAPK / JNK proteins and downregulation of anti-apoptotic ERK1/2, AKT1 and
      HSP27. Treatment with NutramilTM Complex also affected the expression of the BCL2
      family genes. Results also showed down-regulation of anti-apoptotic BCL-2 and up
      regulation of pro-apoptotic members such as BAX, BAD, BID. In addition, we also
      observed regulation of many other genes, including Ikappabetaalpha, Chk1 and
      Chk2, associated with apoptotic events. Taken together, our results suggest
      activation of the mitochondrial apoptotic pathway as most likely mechanism of
      anti-carcinogenic activity of NutramilTM Complex.

PMID- 29444165
TI  - Frequency, trends, and antecedents of severe maternal depression after three
      million U.S. births.
AB  - BACKGROUND: Postpartum depression carries adverse consequences for mothers and
      children, so widespread screening during primary care visits is recommended.
      However, the rates, timing, and factors associated with significant depressive
      episodes are incompletely understood. METHODS AND FINDINGS: We examined the
      Healthcare Cost and Utilization Project (HCUP) State Inpatient, Emergency
      Department, and Ambulatory Surgery and Services Databases from California (2005
      2011) and Florida (2005-2012). Within 203 million records, we identified
      3,213,111 births and all mothers who had hospital encounters for severe
      depression within 40 weeks following delivery. We identified 15,806 episodes of
      postpartum depression after 11,103 deliveries among 10,883 unique women, and
      calculated an overall rate of 36.7 depression- associated hospital visits per
      10,000 deliveries. Upward trends were observed in both states, with combined five
      year increases of 34%. First depressive events were most common within 30 days of
      delivery, but continued for the entire observation period. About half
      (1,661/3,325) of PPD first episodes occurred within 34 days of delivery, 70%
      (2,329/3,325) by the end of the second month, and 87% (2,893/3,325) before four
      months of the delivery. Women with private insurance were less likely to have
      hospital encounters for depression than women with public insurance and women
      with depression were much more likely to have had some kind of hospital encounter
      at some time during their pregnancies. Rates of depression increased with the
      number of prenatal hospital encounters in a "dose-dependent" fashion: the rate of
      depression was 17.2/10,000 for women with no prenatal hospital visits, doubling
      for women with at least one encounter (34.9/10,000), and increasing 7-fold to
      126/10,000 for women with three or more encounters during their pregnancies.
      CONCLUSIONS: Our findings suggest that (1) hospital encounters for post-partum
      depression are increasing, (2) screening should begin very early and continue for
      the first year after delivery, and (3) added attention should be given to women
      who had hospital encounters during their pregnancies.

PMID- 29444164
TI  - Evolution of nodule stiffness might predict response to local ablative therapy: A
      series of patients with hepatocellular carcinoma.
AB  - BACKGROUND: Early information on treatment response of HCC to local ablative
      therapy is crucial. Elastography as a non-invasive method has recently been shown
      to play a potential role in distinguishing between benign and malignant liver
      lesions. Elastography of hepatocellular carcinoma (HCC) in early response to
      local ablative therapy has not been studied to date. METHODS: We prospectively
      included a cohort of 14 patients with diagnosis of HCC who were treated with
      local ablative therapy (transarterial chemoembolization, TACE and/or
      radiofrequency ablation, RFA). We used 2D shear-wave elastography (RT 2D-SWE) to
      examine stiffness of HCC lesion before and 3, 30 and 90 days after local ablative
      therapy. Contrast-enhanced imaging after 90 days was performed to evaluate
      treatment response. Primary endpoint was stiffness of HCC in response to local
      ablative therapy. Secondary end point was tumor recurrence. RESULTS: Stiffness of
      HCC nodules and liver showed no significant difference prior to local ablative
      therapy. As early as three days after treatment, stiffness of responding HCC was
      significantly higher compared to non-responding. Higher stiffness before
      treatment was significantly associated with tumor recurrence. CONCLUSION: Nodule
      stiffness in general and RT 2D-SWE in particular could provide a useful tool for
      early prediction of HCC response to local ablative therapy.

PMID- 29444166
TI  - Fairness informs social decision making in infancy.
AB  - The ability to reason about fairness plays a defining role in the development of
      morality. Thus, researchers have long been interested in understanding when and
      how a sensitivity to fairness first develops. Here, we examined infants' ability
      to use fairness information in selecting social partners. Using a novel
      experimental paradigm that combined pre-recorded stimuli with an active
      behavioral measure, we tested whether infants preferred to socially engage with
      an individual they had previously seen behave fairly or unfairly. After viewing
      an individual distribute goods to third parties either equally (i.e., 3:3
      distribution) or unequally (i.e., 5:1 distribution), both 13- and 17-month-old
      infants selectively chose to engage in a social interaction with (i.e., take a
      toy from) an individual who distributed resources equally. The use of a novel
      paradigm to assess infants' fairness preferences demonstrates that infants'
      previously established fairness preferences extend across different, more
      demanding paradigms, and may therefore be more enduring in nature. Together,
      these findings provide new insights into the nature of infants' fairness
      representations, and fill in key gaps in the developmental timeline of infants'
      ability to use fairness information in their consideration of potential social
      partners. In sum, these findings build on previous research by demonstrating that
      infants not only hold an expectation that resources should be distributed fairly,
      they also preferentially interact with those who have previously done so. The
      early-emerging ability to both reason about and use fairness information may play
      an influential role in the development of complex prosocial behaviors related to
      morality more broadly.

PMID- 29444167
TI  - Rotavirus vaccine coverage and factors associated with uptake using linked data:
      Ontario, Canada.
AB  - BACKGROUND: In August 2011, Ontario, Canada introduced a rotavirus immunization
      program using RotarixTM vaccine. No assessments of rotavirus vaccine coverage
      have been previously conducted in Ontario. METHODS: We assessed vaccine coverage
      (series initiation and completion) and factors associated with uptake using the
      Electronic Medical Record Administrative data Linked Database (EMRALD), a
      collection of family physician electronic medical records (EMR) linked to health
      administrative data. Series initiation (1 dose) and series completion (2 doses)
      before and after the program's introduction were calculated. To identify factors
      associated with series initiation and completion, adjusted odds ratios (aOR) and
      95% confidence intervals (95%CI) were calculated using logistic regression.
      RESULTS: A total of 12,525 children were included. Series completion increased
      each year of the program (73%, 79% and 84%, respectively). Factors associated
      with series initiation included high continuity of care (aOR = 2.15; 95%CI, 1.61
      2.87), maternal influenza vaccination (aOR = 1.55; 95%CI,1.24-1.93), maternal
      immmigration to Canada in the last five years (aOR = 1.47; 95% CI, 1.05-2.04),
      and having no siblings (aOR = 1.62; 95%CI,1.30-2.03). Relative to the first
      program year, infants were more likely to initiate the series in the second year
      (aOR = 1.71; 95% CI 1.39-2.10) and third year (aOR = 2.02; 95% CI 1.56-2.61) of
      the program. Infants receiving care from physicians with large practices were
      less likely to initiate the series (aOR 0.91; 95%CI, 0.88-0.94, per 100 patients
      rostered) and less likely to complete the series (aOR 0.94; 95%CI, 0.91-0.97, per
      100 patients rostered). Additional associations were identified for series
      completion. CONCLUSIONS: Family physician delivery achieved moderately high
      coverage in the program's first three years. This assessment demonstrates the
      usefulness of EMR data for evaluating vaccine coverage. Important insights into
      factors associated with initiation or completion (i.e. high continuity of care,
      smaller roster sizes, rural practice location) suggest areas for research and
      potential program supports.

PMID- 29444168
TI  - Identifying genetic risk loci for diabetic complications and showing evidence for
      heterogeneity of type 1 diabetes based on complications risk.
AB  - There is a growing body of evidence suggesting that type 1 diabetes (T1D) is a
      genetically heterogeneous disease. However, the extent of this heterogeneity, and
      what observations may distinguish different forms, is unclear. One indicator may
      be T1D-related microvascular complications (MVCs), which are familial, but occur
      in some families, and not others. We tested the hypothesis that T1D plus MVC is
      genetically distinct from T1D without MCV. We studied 415 families (2,462
      individuals, 896 with T1D) using genome-wide linkage analysis, comparing families
      with and without MVC. We also tested for interaction between identified loci and
      alleles at the HLA-DRB1 locus. We found significant linkage scores at 1p36.12,
      1q32.1, 8q21.3, 12p11.21 and 22q11.21. In all regions except 1p36.12, linkage
      scores differed between MVC-based phenotype groups, suggesting that families with
      MVCs express different genetic influences than those without. Our linkage results
      also suggested gene-gene interaction between the above putative loci and the HLA
      region; HLA-based strata produced significantly increased linkage scores in some
      strata, but not others within a phenotype group. We conclude that families with
      type 1 diabetes plus MVCs are genetically different from those with diabetes
      alone.

PMID- 29444169
TI  - Monitoring chest compression quality during cardiopulmonary resuscitation: Proof
      of-concept of a single accelerometer-based feedback algorithm.
AB  - BACKGROUND: The use of real-time feedback systems to guide rescuers during
      cardiopulmonary resuscitation (CPR) significantly contributes to improve
      adherence to published resuscitation guidelines. Recently, we designed a novel
      method for computing depth and rate of chest compressions relying solely on the
      spectral analysis of chest acceleration. That method was extensively tested in a
      simulated manikin scenario. The purpose of this study is to report the results of
      this method as tested in human out-of-hospital cardiac arrest (OHCA) cases.
      MATERIALS AND METHODS: The algorithm was evaluated retrospectively with seventy
      five OHCA episodes recorded by monitor-defibrillators equipped with a CPR
      feedback device. The acceleration signal and the compression signal computed by
      the CPR feedback device were stored in each episode. The algorithm was
      continuously applied to the acceleration signals. The depth and rate values
      estimated every 2-s from the acceleration data were compared to the reference
      values obtained from the compression signal. The performance of the algorithm was
      assesed in terms of the sensitivity and positive predictive value (PPV) for
      detecting compressions and in terms of its accuracy through the analysis of
      measurement error. RESULTS: The algorithm reported a global sensitivity and PPV
      of 99.98% and 99.79%, respectively. The median (P75) unsigned error in depth and
      rate was 0.9 (1.7) mm and 1.0 (1.7) cpm, respectively. In 95% of the analyzed 2-s
      windows the error was below 3.5 mm and 3.1 cpm, respectively. CONCLUSIONS: The
      CPR feedback algorithm proved to be reliable and accurate when tested
      retrospectively with human OHCA episodes. A new CPR feedback device based on this
      algorithm could be helpful in the resuscitation field.

PMID- 29444170
TI  - Genotypic and phenotypic characterization of the Sdccag8Tn(sb-Tyr)2161B.CA1C2Ove
      mouse model.
AB  - Nephronophthisis-related ciliopathies (NPHP-RC) are a group of disorders that
      present with end-stage renal failure in childhood/adolescence, kidney cysts,
      retinal degeneration, and cerebellar hypoplasia. One disorder that shares
      clinical features with NPHP-RC is Bardet-Biedl Syndrome (BBS). Serologically
      defined colon cancer antigen 8 (SDCCAG8; also known as NPHP10 and BBS16) is an
      NPHP gene that is also associated with BBS. To better understand the patho
      mechanisms of NPHP and BBS caused by loss of SDCCAG8 function, we characterized
      an SDCCAG8 mouse model (Sdccag8Tn(sb-Tyr)2161B.CA1C2Ove) generated by Sleeping
      Beauty Transposon (SBT)-mediated insertion mutagenesis. Consistent with the
      previously reported, independent SDCCAG8 mouse models, our mutant mice display
      pre-axial polydactyly in their hind limbs. In addition, we report patterning
      defects in the secondary palate, brain abnormalities, as well as neonatal
      lethality associated with developmental defects in the lung in our mouse model.
      The neonatal lethality phenotype is genetic background dependent and rescued by
      introducing 129S6/SvEvTac background. Genetic modifier(s) responsible for this
      effect were mapped to a region between SNPs rs3714172 and rs3141832 on chromosome
      11. While determining the precise genetic lesion in our mouse model, we found
      that SBT insertion resulted in a deletion of multiple exons from both Sdccag8 and
      its neighboring gene Akt3. We ascribe the patterning defects in the limb and the
      secondary palate as well as lung abnormalities to loss of SDCCAG8, while the
      developmental defects in the brain are likely due to the loss of AKT3. This mouse
      model may be useful to study features not observed in other SDCCAG8 models but
      cautions are needed in interpreting data.

PMID- 29444172
TI  - Motor and psychosocial impact of robot-assisted gait training in a real-world
      rehabilitation setting: A pilot study.
AB  - In the last decade robotic devices have been applied in rehabilitation to
      overcome walking disability in neurologic diseases with promising results. Robot
      assisted gait training (RAGT) using the Lokomat seems not only to improve gait
      parameters but also the perception of well-being. Data on the psychosocial
      patient-robot impact are limited, in particular in the real-world of RAGT, in the
      rehabilitation setting. During rehabilitation training, the Lokomat can be
      considered an "assistive device for movement". This allowed the use of the
      Psychosocial Impact of Assistive Device Scale- PIADS to describe patient
      interaction with the Lokomat. The primary aim of this pilot study was to evaluate
      the psychosocial impact of the Lokomat in an in-patient rehabilitation setting
      using the PIADS; secondary aims were to assess whether the psychosocial impact of
      RAGT is different between pathological sub-groups and if the Lokomat influenced
      functional variables (Functional Independence Measure scale-FIM and parameters
      provided by the Lokomat itself). Thirty-nine consecutive patients (69% males,
      54.0+/-18.0 years) eligible for Lokomat training, with etiologically
      heterogeneous walking disabilities (Parkinson's Disease, n = 10; Spinal Cord
      Injury, n = 21; Ictus Event, n = 8) were enrolled. Patients were assessed with
      the FIM before and after rehabilitation with Lokomat, and the PIADS was
      administered after the rehabilitative period with Lokomat. Overall the PIADS
      score was positive (35.8+/-21.6), as well as the three sub-scales, pertaining to
      "ability", "adaptability" and "self-esteem" (17.2+/-10.4, 8.9+/-5.5 and 10.1+/
      6.6 respectively) with no between-group differences. All patients significantly
      improved in gait measure and motor FIM scale (difference after-before treatment
      values: 11.7+/-9.8 and 11.2+/-10.3 respectively), increased treadmill speed (0.4
      +/- 0.2m/s), reduced body weight support (-14.0+/-9.5%) and guidance force (-13.1
      +/- 10.7%). This pilot study indicates that Lokomat, in a real-world in-patient
      setting, may have a generalised approval, independent of disease, underlining the
      importance of the psycho-social framework for patients training with assistive
      robotic-devices.

PMID- 29444171
TI  - Reduced cognitive function, increased blood-brain-barrier transport and
      inflammatory responses, and altered brain metabolites in LDLr -/-and C57BL/6 mice
      fed a western diet.
AB  - Recent work suggests that diet affects brain metabolism thereby impacting
      cognitive function. Our objective was to determine if a western diet altered
      brain metabolism, increased blood-brain barrier (BBB) transport and inflammation,
      and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein
      receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline.
      We show that a western diet and LDLr -/- moderately influence cognitive processes
      as assessed by Y-maze and radial arm water maze. Also, western diet significantly
      increased BBB transport, as well as microvessel factor VIII in LDLr -/- and
      microglia IBA1 staining in WT, both indicators of activation and
      neuroinflammation. Interestingly, LDLr -/- mice had a significant increase in 18F
      fluorodeoxyglucose uptake irrespective of diet and brain 1H-magnetic resonance
      spectroscopy showed increased lactate and lipid moieties. Metabolic assessments
      of whole mouse brain by GC/MS and LC/MS/MS showed that a western diet altered
      brain TCA cycle and beta-oxidation intermediates, levels of amino acids, and
      complex lipid levels and elevated proinflammatory lipid mediators. Our study
      reveals that the western diet has multiple impacts on brain metabolism,
      physiology, and altered cognitive function that likely manifest via multiple
      cellular pathways.

PMID- 29444173
TI  - Transcriptome variations among human embryonic stem cell lines are associated
      with their differentiation propensity.
AB  - Human embryonic stem cells (hESCs) have the potential to form any cell type in
      the body, making them attractive cell sources in drug screening, regenerative
      medicine, disease and developmental processes modeling. However, not all hESC
      lines have the equal potency to generate desired cell types in vitro. Significant
      variations have been observed for the differentiation efficiency of various human
      ESC lines. The precise underpinning molecular mechanisms are still unclear. In
      this work, we compared transcriptome variations of four hESC lines H7, HUES1,
      HUES8 and HUES9. We found that hESC lines have different gene expression
      profiles, and these differentially expressed genes (DEGs) are significantly
      enriched in developmental processes, such as ectodermal, mesodermal and
      endodermal development. The enrichment difference between hESC lines was
      consistent with its lineage bias. Among these DEGs, some pluripotency factors and
      genes involved in signaling transduction showed great variations as well. The
      pleiotropic functions of these genes in controlling hESC identity and early
      lineage specification, implicated that different hESC lines may utilize distinct
      balance mechanisms to maintain pluripotent state. When the balance is broken in a
      certain environment, gene expression variation between them could impact on their
      different lineage specification behavior.

PMID- 29444174
TI  - Chromosome evolution in Cophomantini (Amphibia, Anura, Hylinae).
AB  - The hylid tribe Cophomantini is a diverse clade of Neotropical treefrogs composed
      of the genera Aplastodiscus, Boana, Bokermannohyla, Hyloscirtus, and Myersiohyla.
      The phylogenetic relationships of Cophomantini have been comprehensively reviewed
      in the literature, providing a suitable framework for the study of chromosome
      evolution. Employing different banding techniques, we studied the chromosomes of
      25 species of Boana and 3 of Hyloscirtus; thus providing, for the first time,
      data for Hyloscirtus and for 15 species of Boana. Most species showed karyotypes
      with 2n = 2x = 24 chromosomes; some species of the B. albopunctata group have 2n
      = 2x = 22, and H. alytolylax has 2n = 2x = 20. Karyotypes are all bi-armed in
      most species presented, with the exception of H. larinopygion (FN = 46) and H.
      alytolylax (FN = 38), with karyotypes that have a single pair of small
      telocentric chromosomes. In most species of Boana, NORs are observed in a single
      pair of chromosomes, mostly in the small chromosomes, although in some species of
      the B. albopunctata, B. pulchella, and B. semilineata groups, this marker occurs
      on the larger pairs 8, 1, and 7, respectively. In Hyloscirtus, NOR position
      differs in the three studied species: H. alytolylax (4p), H. palmeri (4q), and H.
      larinopygion (1p). Heterochromatin is a variable marker that could provide
      valuable evidence, but it would be necesserary to understand the molecular
      composition of the C-bands that are observed in different species in order to
      test its putative homology. In H. alytolylax, a centromeric DAPI+ band was
      observed on one homologue of chromosome pair 2. The band was present in males but
      absent in females, providing evidence for an XX/XY sex determining system in this
      species. We review and discuss the importance of the different chromosome markers
      (NOR position, C-bands, and DAPI/CMA3 patterns) for their impact on the taxonomy
      and karyotype evolution in Cophomantini.

PMID- 29444176
TI  - Lack of usefulness of computed tomography for surveillance in patients with
      aggressive non-Hodgkin lymphoma.
AB  - Surveillance computed tomography (CT) is usual practice for patients with
      aggressive non-Hodgkin lymphoma (aNHL) in complete remission (CR). However,
      evidence to support this strategy is lacking. We retrospectively analyzed our
      institutional lymphoma registry, including patients with lymphoma consecutively
      enrolled from June 1995 to October 2016. Of 1,385 patients with aNHL, 664
      achieved CR and were followed up with or without surveillance CT. Surveillance CT
      was performed for 609 patients every 3 or 6 months for the first 2 years, then
      every 6 or 12 months thereafter. Relapse was detected in 171 patients, of whom
      152 underwent surveillance CT during follow-up. Of these 152 patients,
      asymptomatic relapse was detected in 67 (44%) using surveillance CT, and
      symptomatic relapse outside the surveillance interval was detected in the
      remaining 85 (56%). Detection of asymptomatic relapse using surveillance CT did
      not improve the overall or post-relapse survival in patients with relapsed aNHL.
      Surveillance CT interval (3 or 6 months) did not affect survival. No subgroups
      were identified that favored the use of surveillance CT to detect relapse. The
      results of this study suggest that routine surveillance CT in patients with aNHL
      to detect asymptomatic relapse might have a limited role in improving survival.
      CT is recommended when a relapse is clinically suspected.

PMID- 29444175
TI  - Tomographic optical imaging of cortical responses after crossing nerve transfer
      in mice.
AB  - To understand the neural mechanisms underlying the therapeutic effects of
      crossing nerve transfer for brachial plexus injuries in human patients, we
      investigated the cortical responses after crossing nerve transfer in mice using
      conventional and tomographic optical imaging. The distal cut ends of the left
      median and ulnar nerves were connected to the central cut ends of the right
      median and ulnar nerves with a sciatic nerve graft at 8 weeks of age. Eight weeks
      after the operation, the responses in the primary somatosensory cortex (S1)
      elicited by vibratory stimulation applied to the left forepaw were visualized
      based on activity-dependent flavoprotein fluorescence changes. In untreated mice,
      the cortical responses to left forepaw stimulation were mainly observed in the
      right S1. In mice with nerve crossing transfer, cortical responses to left
      forepaw stimulation were observed in the left S1 together with clear cortical
      responses in the right S1. We expected that the right S1 responses in the
      untreated mice were produced by thalamic inputs to layer IV, whereas those in the
      operated mice were mediated by callosal inputs from the left S1 to layer II/III
      of the right S1. To confirm this hypothesis, we performed tomographic imaging of
      flavoprotein fluorescence responses by macroconfocal microscopy. Flavoprotein
      fluorescence responses in layer IV were dominant compared to those in layer
      II/III in untreated mice. In contrast, responses in layer II/III were dominant
      compared to those in layer IV in operated mice. The peak latency of the cortical
      responses in the operated mice was longer than that in the untreated mice. These
      results confirmed our expectation that drastic reorganization in the cortical
      circuits was induced after crossing nerve transfer in mice.

PMID- 29444178
TI  - Heterogeneity in pulmonary emphysema: Analysis of CT attenuation using Gaussian
      mixture model.
AB  - PURPOSE: To utilize Gaussian mixture model (GMM) for the quantification of
      chronic obstructive pulmonary disease (COPD) and to evaluate the combined use of
      multiple types of quantification. MATERIALS AND METHODS: Eighty-seven patients
      (67 men, 20 women; age, 67.4 +/- 11.0 years) who had undergone computed
      tomography (CT) and pulmonary function test (PFT) were included. The
      heterogeneity of CT attenuation in emphysema (HC) was obtained by analyzing a
      distribution of CT attenuation with GMM. The percentages of low-attenuation
      volume in the lungs (LAV), wall area of bronchi (WA), and the cross-sectional
      area of small pulmonary vessels (CSA) were also calculated. The relationships
      between COPD quantifications and the PFT results were evaluated by Pearson's
      correlation coefficients and through linear models, with the best models selected
      using Akaike information criterion (AIC). RESULTS: The correlation coefficients
      with FEV1 were as follows: LAV, -0.505; HC, -0.277; CSA, 0.384; WA, -0.196. The
      correlation coefficients with FEV1/FVC were: LAV, -0.640; HC, -0.136; CSA, 0.288;
      WA, -0.131. For predicting FEV1, the smallest AIC values were obtained in the
      model with LAV, HC, CSA, and WA. For predicting FEV1/FVC, the smallest AIC values
      were obtained in the model with LAV and HC. In both models, the coefficient of HC
      was statistically significant (P-values = 0.000880 and 0.0441 for FEV1 and
      FEV1/FVC, respectively). CONCLUSION: GMM was applied to COPD quantification. The
      results of this study show that COPD severity was associated with HC. In
      addition, it is shown that the combined use of multiple types of quantification
      made the evaluation of COPD severity more reliable.

PMID- 29444177
TI  - Kidney-differentiated cells derived from Lowe Syndrome patient's iPSCs show
      ciliogenesis defects and Six2 retention at the Golgi complex.
AB  - Lowe syndrome is an X-linked condition characterized by congenital cataracts,
      neurological abnormalities and kidney malfunction. This lethal disease is caused
      by mutations in the OCRL1 gene, which encodes for the phosphatidylinositol 5
      phosphatase Ocrl1. While in the past decade we witnessed substantial progress in
      the identification and characterization of LS patient cellular phenotypes, many
      of these studies have been performed in knocked-down cell lines or patient's
      cells from accessible cell types such as skin fibroblasts, and not from the
      organs affected. This is partially due to the limited accessibility of patient
      cells from eyes, brain and kidneys. Here we report the preparation of induced
      pluripotent stem cells (iPSCs) from patient skin fibroblasts and their
      reprogramming into kidney cells. These reprogrammed kidney cells displayed
      primary cilia assembly defects similar to those described previously in cell
      lines. Additionally, the transcription factor and cap mesenchyme marker Six2 was
      substantially retained in the Golgi complex and the functional nuclear-localized
      fraction was reduced. These results were confirmed using different batches of
      differentiated cells from different iPSC colonies and by the use of the human
      proximal tubule kidney cell line HK2. Indeed, OCRL1 KO led to both ciliogenesis
      defects and Six2 retention in the Golgi complex. In agreement with Six2's role in
      the suppression of ductal kidney lineages, cells from this pedigree were over
      represented among patient kidney-reprogrammed cells. We speculate that this
      diminished efficacy to produce cap mesenchyme cells would cause LS patients to
      have difficulties in replenishing senescent or damaged cells derived from this
      lineage, particularly proximal tubule cells, leading to pathological scenarios
      such as tubular atrophy.

PMID- 29444179
TI  - Capability beliefs on, and use of evidence-based practice among four health
      professional and student groups in geriatric care: A cross sectional study.
AB  - Implementation of evidence-based practice (EBP) is a complex task. This study,
      conducted in an acute geriatric setting, aims to compare self-reported capability
      beliefs on EBP between health professionals and students, and to compare the use
      of EBP between health professional groups. Occupational therapists, physicians,
      physiotherapists and registered nurses with three or more months' employment, and
      all students from the occupational therapy, medical, physiotherapy and nursing
      programs, who had conducted workplace learning at the department, were invited.
      Data on capability beliefs and use of EBP were collected using the Evidence-based
      Practice Capabilities Beliefs Scale assessing six activities of EBP: formulate
      questions; search databases; search other sources; appraise research reports;
      participate in implementation in practice; and participate in evaluation.
      Descriptive and inferential statistics were used. Capability beliefs on EBP: The
      health professionals (n = 101; response rate 80%) reported high on search other
      sources but less on appraise research reports. The students (n = 124; response
      rate 73%) reported high on all EBP activities. The health professionals reported
      significantly higher on search other sources than the students. The students
      reported significantly higher on formulate questions and appraise research
      reports than the health professionals. No significant differences were identified
      between the health professional groups or between the student groups. Use of EBP:
      Health professionals reported wide-ranging use from several times each month to
      once every six months. The physicians reported significantly more frequent use
      than registered nurses and occupational therapists. Health professionals
      supervising students reported more frequent use of appraise research reports than
      the non-supervising group. There is a need for improving the use of EBP,
      particularly among registered nurses and occupational therapists. Supervision of
      students might enhance the motivation among staff to increase the use of EBP and
      students' high EBP capability beliefs might inspire staff in this matter.

PMID- 29444180
TI  - The Bogazici face database: Standardized photographs of Turkish faces with
      supporting materials.
AB  - Many sets of human facial photographs produced in Western cultures are available
      for scientific research. We report here on the development of a face database of
      Turkish undergraduate student targets. High-resolution standardized photographs
      were taken and supported by the following materials: (a) basic demographic and
      appearance-related information, (b) two types of landmark configurations (for
      Webmorph and geometric morphometrics (GM)), (c) facial width-to-height ratio
      (fWHR) measurement, (d) information on photography parameters, (e) perceptual
      norms provided by raters. We also provide various analyses and visualizations of
      facial variation based on rating norms using GM. Finally, we found that there is
      sexual dimorphism in fWHR in our sample but that this is accounted for by body
      mass index. We present the pattern of associations between rating norms, GM and
      fWHR measurements. The database and supporting materials are freely available for
      scientific research purposes.

PMID- 29444181
TI  - Correction: Early- and later-phases satellite cell responses and myonuclear
      content with resistance training in young men.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0191039.].

PMID- 29444182
TI  - Towards phenotyping stroke: Leveraging data from a large-scale epidemiological
      study to detect stroke diagnosis.
AB  - OBJECTIVE: 1) To develop a machine learning approach for detecting stroke cases
      and subtypes from hospitalization data, 2) to assess algorithm performance and
      predictors on real-world data collected by a large-scale epidemiology study in
      the US; and 3) to identify directions for future development of high-precision
      stroke phenotypic signatures. MATERIALS AND METHODS: We utilized 8,131
      hospitalization events (ICD-9 codes 430-438) collected from the Greater
      Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Detailed information
      from patients' medical records was abstracted for each event by trained research
      nurses. By analyzing the broad list of demographic and clinical variables, the
      machine learning algorithms predicted whether an event was a stroke case and, if
      so, the stroke subtype. The performance was validated on gold-standard labels
      adjudicated by stroke physicians, and results were compared with stroke
      classifications based on ICD-9 discharge codes, as well as labels determined by
      study nurses. RESULTS: The best performing machine learning algorithm achieved a
      performance of 88.57%/93.81%/92.80%/93.30%/89.84%/98.01%
      (accuracy/precision/recall/F-measure/area under ROC curve/area under precision
      recall curve) on stroke case detection. For detecting stroke subtypes, the
      algorithm yielded an overall accuracy of 87.39% and greater than 85% precision on
      individual subtypes. The machine learning algorithms significantly outperformed
      the ICD-9 method on all measures (P value<0.001). Their performance was
      comparable to that of study nurses, with better tradeoff between precision and
      recall. The feature selection uncovered a subset of predictive variables that
      could facilitate future development of effective stroke phenotyping algorithms.
      DISCUSSION AND CONCLUSIONS: By analyzing a broad array of patient data, the
      machine learning technologies held promise for improving detection of stroke
      diagnosis, thus unlocking high statistical power for subsequent genetic and
      genomic studies.

PMID- 29444183
TI  - Nanoparticle-antagomiR based targeting of miR-31 to induce osterix and
      osteocalcin expression in mesenchymal stem cells.
AB  - Mesenchymal stem cells are multipotent adult stem cells capable of generating
      bone, cartilage and fat, and are thus currently being exploited for regenerative
      medicine. When considering osteogenesis, developments have been made with regards
      to chemical induction (e.g. differentiation media) and physical induction (e.g.
      material stiffness, nanotopography), targeting established early transcription
      factors or regulators such as runx2 or bone morphogenic proteins and promoting
      increased numbers of cells committing to osteo-specific differentiation. Recent
      research highlighted the involvement of microRNAs in lineage commitment and
      terminal differentiation. Herein, gold nanoparticles that confer stability to
      short single stranded RNAs were used to deliver MiR-31 antagomiRs to both pre
      osteoblastic cells and primary human MSCs in vitro. Results showed that blocking
      miR-31 led to an increase in osterix protein in both cell types at day 7, with an
      increase in osteocalcin at day 21, suggesting MSC osteogenesis. In addition, it
      was noted that antagomiR sequence direction was important, with the 5 prime
      reading direction proving more effective than the 3 prime. This study highlights
      the potential that miRNA antagomiR-tagged nanoparticles offer as novel
      therapeutics in regenerative medicine.

PMID- 29444184
TI  - Qualitative thematic analysis of the phenomenology of near-death experiences.
AB  - Near-death experiences (NDEs) refer to profound psychological events that can
      have an important impact on the experiencers' (NDErs) lives. Previous studies
      have shown that NDEs memories are phenomenologically rich. In the present study,
      we therefore aimed to extract the common themes (referred to as "features" in the
      NDE literature) reported by NDErs by analyzing all the concepts stored in the
      narratives of their experiences. A qualitative thematic analysis has been carried
      out on 34 cardiac arrest survivors' NDE narratives. Our results shed the light on
      the structure of the narratives by identifying 10 "time-bounded" themes which
      refer to isolated events encountered during the NDE and 1 "transversal" theme
      which characterizes the whole narrative and generally appears as a retrospective
      comment of self-reflection on the experience. The division of narratives into
      themes provides us with detailed information about the vocabulary used by NDErs
      to describe their experience. This established thematic method enables a rigorous
      description of the phenomenon, ensuring the inclusion of all self-reported
      manifestations of themes in narratives.

PMID- 29444185
TI  - Humoral and cell-mediated immune responses after a booster dose of HBV vaccine in
      HIV-infected children, adolescents and young adults.
AB  - OBJECTIVE: HBV vaccine induces protective antibodies only in 23-56% of HIV
      infected children. The aim of our study is to evaluate the immunologic effects of
      a booster dose of HBV vaccine in HIV-infected youth. DESIGN: 53 young HIV
      infected patients in whom HBV vaccination did not elicit protective Ab titers
      were enrolled. All patients were on ART with optimal immunological and viral
      response. METHOD: All patients received a booster dose of HBV vaccine (HBVAXPRO
      10 MUg i.m.). HBV-specific Ab titer, viral load and CD4+ T cells were measured at
      baseline (T0), T1, T6 and T12 months. In a subgroup of 16 patients HBV-specific
      cell mediated immune responses were evaluated at baseline, at T1 and T6. RESULTS:
      The booster dose induced seroconversion in 51% of patients at T1, 57% at T6,
      and49% at T12; seroconversion rate was significantly correlated with CD4+T cells
      at T0 and to the CD4 nadir. The booster dose induced HBV-specific cell mediated
      immunity at T6 mainly in Responders (Rs): Effector Memory CD8+T cells, HBV
      specific TNFalpha-, IFNgamma-, granzyme secreting CD8+ T cells and IL2-secreting
      CD4+ T cells were significantly increased in Rs compared to T0. In Non Responders
      (NRs), HBV-specific IL2-secreting CD4+ T cells, Central and Effector Memory CD8+
      T cells were the only parameters modified at T6. CONCLUSIONS: Seroconversion
      induced by a booster dose of vaccine correlates with the development of T cell
      immunological memory in HIV-infected patients who did not respond to the standard
      immunization. Alternate immunization schedules need to be considered in NRs.

PMID- 29444186
TI  - Identification of fungi in shotgun metagenomics datasets.
AB  - Metagenomics uses nucleic acid sequencing to characterize species diversity in
      different niches such as environmental biomes or the human microbiome. Most
      studies have used 16S rRNA amplicon sequencing to identify bacteria. However, the
      decreasing cost of sequencing has resulted in a gradual shift away from amplicon
      analyses and towards shotgun metagenomic sequencing. Shotgun metagenomic data can
      be used to identify a wide range of species, but have rarely been applied to
      fungal identification. Here, we develop a sequence classification pipeline,
      FindFungi, and use it to identify fungal sequences in public metagenome datasets.
      We focus primarily on animal metagenomes, especially those from pig and mouse
      microbiomes. We identified fungi in 39 of 70 datasets comprising 71 fungal
      species. At least 11 pathogenic species with zoonotic potential were identified,
      including Candida tropicalis. We identified Pseudogymnoascus species from 13
      Antarctic soil samples initially analyzed for the presence of bacteria capable of
      degrading diesel oil. We also show that Candida tropicalis and Candida loboi are
      likely the same species. In addition, we identify several examples where
      contaminating DNA was erroneously included in fungal genome assemblies.

PMID- 29444187
TI  - A real-time monitoring platform of myogenesis regulators using double fluorescent
      labeling.
AB  - Real-time, quantitative measurement of muscle progenitor cell (myoblast)
      differentiation is an important tool for skeletal muscle research and
      identification of drugs that support skeletal muscle regeneration. While most
      quantitative tools rely on sacrificial approach, we developed a double
      fluorescent tagging approach, which allows for dynamic monitoring of myoblast
      differentiation through assessment of fusion index and nuclei count. Fluorescent
      tagging of both the cell cytoplasm and nucleus enables monitoring of cell fusion
      and the formation of new myotube fibers, similar to immunostaining results. This
      labeling approach allowed monitoring the effects of Myf5 overexpression,
      TNFalpha, and Wnt agonist on myoblast differentiation. It also enabled testing
      the effects of surface coating on the fusion levels of scaffold-seeded myoblasts.
      The double fluorescent labeling of myoblasts is a promising technique to
      visualize even minor changes in myogenesis of myoblasts in order to support
      applications such as tissue engineering and drug screening.

PMID- 29444188
TI  - Switching and loss of cellular cytokine producing capacity characterize in vivo
      viral infection and malignant transformation in human T- lymphotropic virus type
      1 infection.
AB  - Adult T-cell leukaemia/lymphoma (ATL) arises from chronic non-malignant human T
      lymphotropic virus type-1 (HTLV-1) infection which is characterized by high
      plasma pro-inflammatory cytokines whereas ATL is characterized by high plasma
      anti-inflammatory (IL-10) concentrations. The poor prognosis of ATL is partly
      ascribed to disease-associated immune suppression. ATL cells have a CD4+CCR4+CD26
      CD7- immunophenotype but infected cells with this immunophenotype ('ATL-like'
      cells) are also present in non-malignant HTLV-1 infection. We hypothesized that
      'ATL-like' and ATL cells have distinct cytokine producing capacity and a switch
      in the cytokines produced occurs during leukemogenesis. Seventeen asymptomatic
      carriers (ACs), 28 patients with HTLV-1-associated myelopathy (HAM) and 28 with
      ATL were studied. Plasma IL-10 concentration and the absolute frequency of IL-10
      producing CD4+ T cells were significantly higher in patients with ATL compared to
      AC. IL-10-producing ATL cells were significantly more frequent than 'ATL-like'
      cells. The cytokine-producing cells were only a small fraction of ATL cells.
      Clonality analysis revealed that even in patients with ATL the ATL cells were
      composed not only of a single dominant clone (putative ATL cells) but also tens
      of non-dominant infected clones ('ATL-like' cells). The frequency of cytokine
      producing cells showed a strong inverse correlation with the relative abundance
      of the largest clone in ATL cells suggesting that the putative ATL cells were
      cytokine non-producing and that the 'ATL-like' cells were the primary cytokine
      producers. These findings were confirmed by RNAseq with cytokine mRNA expression
      in ATL cells in patients with ATL (confirmed to be composed of both putative ATL
      and 'ATL-like' cells by TCR analysis) significantly lower compared to 'ATL-like'
      cells in patients with non-malignant HTLV-1 infection (confirmed to be composed
      of hundreds of non-dominant clones by TCR analysis). A significant inverse
      correlation between the relative abundance of the largest clone and cytokine mRNA
      expression was also confirmed. Finally, 'ATL-like' cells produced less pro- and
      more anti-inflammatory cytokines than non 'ATL-like' CD4+ cells (which are
      predominantly HTLV uninfected). In summary, HTLV-1 infection of CD4+ T cells is
      associated with a change in cytokine producing capacity and dominant malignant
      clonal growth is associated with loss of cytokine producing capacity. Non
      dominant clones with 'ATL-like' cells contribute to plasma cytokine profile in
      patients with non-malignant HTLV-1 infection and are also present in patient with
      ATL.

PMID- 29444189
TI  - Cross-priming induces immunodomination in the presence of viral MHC class I
      inhibition.
AB  - Viruses have evolved mechanisms of MHCI inhibition in order to evade recognition
      by cytotoxic CD8+ T cells (CTLs), which is well-illustrated by our prior studies
      on cowpox virus (CPXV) that encodes potent MHCI inhibitors. Deletion of CPXV
      viral MHCI inhibitors markedly attenuated in vivo infection due to effects on CTL
      effector function, not priming. However, the CTL response to CPXV in C57BL/6 mice
      is dominated by a single peptide antigen presented by H-2Kb. Here we evaluated
      the effect of viral MHCI inhibition on immunodominant (IDE) and subdominant
      epitopes (SDE) as this has not been thoroughly examined. We found that cross
      priming, but not cross-dressing, is the main mechanism driving IDE and SDE CTL
      responses following CPXV infection. Secretion of the immunodominant antigen was
      not required for immunodominance. Instead, immunodominance was caused by CTL
      interference, known as immunodomination. Both immunodomination and cross-priming
      of SDEs were not affected by MHCI inhibition. SDE-specific CTLs were also capable
      of exerting immunodomination during primary and secondary responses, which was in
      part dependent on antigen abundance. Furthermore, CTL responses directed solely
      against SDEs protected against lethal CPXV infection, but only in the absence of
      the CPXV MHCI inhibitors. Thus, both SDE and IDE responses can contribute to
      protective immunity against poxviruses, implying that these principles apply to
      poxvirus-based vaccines.

PMID- 29444191
TI  - Restoration of services in disrupted infrastructure systems: A network science
      approach.
AB  - Due to the ubiquitous nature of disruptive extreme events, functionality of the
      critical infrastructure systems (CIS) is constantly at risk. In case of a
      disruption, in order to minimize the negative impact to the society, service
      networks operating on the CIS should be restored as quickly as possible. In this
      paper, we introduce a novel network science inspired measure to quantify the
      criticality of components within a disrupted service network and develop a
      restoration heuristic (Cent-Restore) that prioritizes restoration efforts based
      on this measure. As an illustrative case study, we consider a road network
      blocked by debris in the aftermath of a natural disaster. The debris obstructs
      the flow of relief aid and search-and-rescue teams between critical facilities
      and disaster sites, debilitating the emergency service network. In this context,
      the problem is defined as finding a schedule to clear the roads with the limited
      resources. First, we develop a mixed-integer programming model for the problem.
      Then we validate the efficiency and accuracy of the Cent-Restore heuristic on
      randomly generated instances by comparing it to the model. Furthermore, we use
      Cent-Restore to recommend real-time restoration plans for disrupted road networks
      of Boston and Manhattan and analyze the performance of the plans over time
      through resilience curves. We compare Cent-Restore to the current restoration
      guidelines proposed by FEMA and other strategies that prioritize the restoration
      efforts based on different measures. As a result we confirm the importance of
      including specific post-disruption attributes of the networks to create effective
      restoration strategies. Moreover, we explore the relationship between a service
      network's resilience and its topological and operational characteristics under
      different disruption scenarios. The methods and insights provided in this work
      can be extended to other disrupted large-scale critical infrastructure systems in
      which the ultimate goal is to enable the functions of the overlaying service
      networks.

PMID- 29444192
TI  - Correction: Exploring the Relationship between Experiential Avoidance, Coping
      Functions and the Recency and Frequency of Self-Harm.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0159854.].

PMID- 29444190
TI  - Bone marrow mesenchymal stem cell-derived exosomal miR-21 protects C-kit+ cardiac
      stem cells from oxidative injury through the PTEN/PI3K/Akt axis.
AB  - Stem cell (SC) therapy for ischemic cardiomyopathy is hampered by poor survival
      of the implanted cells. Recently, SC-derived exosomes have been shown to
      facilitate cell proliferation and survival by transporting various proteins and
      non-coding RNAs (such as microRNAs and lncRNAs). In this study, miR-21 was highly
      enriched in exosomes derived from bone marrow mesenchymal stem cells (MSCs).
      Interestingly, exosomes collected from hydrogen peroxide (H2O2)-treated MSCs (H
      Exo) contained higher levels of miR-21 than exosomes released from MSCs under
      normal conditions (N-Exo). The pre-treatment of C-kit+ cardiac stem cells (CSCs)
      with H-Exos resulted in significantly increased levels of miR-21 and phosphor-Akt
      (pAkt) and decreased levels of PTEN, which is a known target of miR-21. AnnexinV
      FITC/PI analysis further demonstrated that the degree of oxidative stress-induced
      apoptosis was markedly lower in H-Exo-treated C-kit+ CSCs than that in N-Exo
      treated cells. These protective effects could be blocked by both a miR-21
      inhibitor and the PI3K/Akt inhibitor LY294002. Therefore, exosomal miR-21 derived
      from H2O2-treated MSCs could be transported to C-kit+ cardiac stem cells to
      functionally inhibit PTEN expression, thereby activating PI3K/AKT signaling and
      leading to protection against oxidative stress-triggered cell death. Thus,
      exosomes derived from MSCs could be used as a new therapeutic vehicle to
      facilitate C-kit+ CSC therapies in the ischemic myocardium.

PMID- 29444194
TI  - Scratching Beneath the Surface.

PMID- 29444195
TI  - Decrease in Inpatient Telemetry Utilization Through a System-Wide Electronic
      Health Record Change and a Multifaceted Hospitalist Intervention.
AB  - BACKGROUND: Unnecessary telemetry monitoring contributes to healthcare waste.
      OBJECTIVE: To evaluate the impact of 2 interventions to reduce telemetry
      utilization. DESIGN, SETTING, PATIENTS: A 2-group retrospective, observational
      pre- to postintervention study of 35,871 nonintensive care unit (ICU) patients
      admitted to 1 academic medical center. INTERVENTION: On the hospitalist service,
      we implemented a telemetry reduction intervention including education, process
      change, routine feedback, and a financial incentive between January 2015 and June
      2015. In July 2015, a system-wide change to the telemetry ordering process was
      introduced. MEASUREMENTS: The primary outcome was telemetry utilization, measured
      as the percentage of daily room charges for telemetry. Secondary outcomes were
      mortality, escalation of care, code event rate, and appropriateness of telemetry
      utilization. Generalized linear models were used to evaluate changes in outcomes
      while adjusting for patient factors. RESULTS: Among hospitalist service patients,
      telemetry utilization was reduced by 69% (95% confidence interval [CI], -72% to 
      64%; P < .001), whereas on other services the reduction was a less marked 22%
      (95% CI, -27% to -16%; P < .001). There were no significant increases in
      mortality, code event rates, or care escalation, and there was a trend toward
      improved utilization appropriateness. CONCLUSIONS: Although electronic telemetry
      ordering changes can produce decreases in hospital-wide telemetry monitoring, a
      multifaceted intervention may lead to an even larger decline in utilization
      rates. Whether these changes are durable cannot be ascertained from our study.

PMID- 29444196
TI  - Days of Therapy Avoided: A Novel Method for Measuring the Impact of an
      Antimicrobial Stewardship Program to Stop Antibiotics.

PMID- 29444197
TI  - A Single, Post-ACTH Cortisol Measurement to Screen for Adrenal Insufficiency in
      the Hospitalized Patient.
AB  - BACKGROUND: Cosyntropin stimulation testing (CST) is used to screen patients for
      adrenal insufficiency (AI). Traditionally, CST includes baseline cortisol
      concentration, the administration of cosyntropin, and cortisol concentration at
      30 and 60 minutes poststimulation. There is debate surrounding the utility of
      testing and cut-off points for concentrations at each time point. OBJECTIVE: To
      determine if a single cortisol measurement at 30 or 60 minutes could replace the
      traditional approach. DESIGN: looked retrospectively at inpatients who underwent
      standard, high-dose CST (n = 702) and evaluated the number of patients who would
      screen positive for AI by using a single time point (30 or 60 minutes) compared
      with the traditional CST. SETTING: A tertiary-care, academic medical center.
      PATIENTS: Hospital inpatients present between January 2012 and September 2013.
      RESULTS: Of tests, 84.3% were normal, which was defined as at least 1 cortisol
      concentration of 18 mcg/dL or higher at any time after stimulation. The average
      60-minute concentration was higher than the average 30-minute concentration (P <
      .001). A single 60-minute concentration is 100% concordant with the full CST in
      the intensive care unit (ICU) subgroup and 99.6% concordant in floor patients. A
      single 30-minute concentration is significantly less concordant, 91.9% and 86.9%,
      in the ICU and floor subgroups, respectively. CONCLUSIONS: Overall, a single 60
      minute cortisol concentration to screen for AI was 99.7% concordant with the
      traditional CST, and the positive percent agreement was 98%. Fewer false-positive
      screens would occur with a single 60-minute cortisol concentration compared with
      a single 30-minute concentration (P < .001). High-dose CST screening may safely
      be interpreted with single 60-minute poststimulation cortisol serum
      concentrations.

PMID- 29444198
TI  - Alveolar Ridge Augmentation with Three-Dimensional Printed Hydroxyapatite
      Devices: A Preclinical Study.
AB  - The objective of this study was to evaluate the effectiveness of precise three
      dimensional hydroxyapatite printed micro- and macrochannel devices for alveolar
      ridge augmentation in a canine model. All grafts induced minimal inflammatory and
      fibrotic reactions. Examination of undecalcified sections revealed that both
      types of grafts demonstrated bone ingrowth. The majority of the bone growth into
      the block graft was into the channels, though a portion grew directly into the
      construct in the form of small bony spicules. In conclusion, bone ingrowth was
      readily demonstrated in the middle of the implanted printed devices.

PMID- 29444199
TI  - Exposure to hexavalent chromium in welders: Results of the WELDOX II field study.
AB  - Objectives: Exposure to hexavalent chromium (Cr(VI)) has been primarily studied
      in chromate production. Here, we measured personal exposure to respirable Cr(VI)
      together with airborne and urinary Cr and Ni in welders to explore levels and
      associations between various measures of exposure. Methods : Shift concentrations
      of Cr(VI), Cr, and Ni were measured in respirable welding fumes in 50 men who
      used either gas metal arc welding (GMAW) (n = 24) or tungsten inert gas welding
      (TIG) (n = 19) as their major technique. Cr and Ni were determined in pre- and
      post-shift urine samples. Concentrations below the limit of quantification (LOQ)
      were multiply imputed. Spearman correlation coefficients (rs) were calculated
      with 95% confidence intervals (CIs) to explore associations between the exposure
      variables, and regression models were applied to estimate the effect of the
      parent metal on the urinary concentration. Results : Regarding the respirable
      Cr(VI), 62% of the measurements were below the LOQ, the 75th percentile was 0.50
      ug m-3, and 8 out of 50 (16%) welders exceeded 1 ug m-3. The highest shift
      concentration that occurred as a result of shielded metal arc welding (SMAW) was
      180 ug m-3. The Cr(VI) content in total Cr ranged from 4 to 82% (median 20%),
      although the concentration correlated with total Cr (rs 0.55, 95% CI 0.46; 0.64).
      The correlation between Cr(VI) and Ni was weaker (rs 0.42, 95% CI 0.34; 0.51)
      than that between total Cr and Ni in welding fumes (rs 0.83, 95% CI 0.74; 0.92).
      Both Cr(VI) and total Cr influenced the urinary Cr concentrations in post-shift
      samples (P = 0.0008 and P <= 0.0001, respectively). The airborne shift exposure
      was a weaker determinant than the Cr content in pre-shift urine samples, which
      strongly correlated with post-shift urinary Cr (rs 0.78, 95% CI 0.69; 0.87).
      Conclusions : The Cr(VI) content in total Cr varied considerably in welding
      fumes. The majority of welders using GMAW or TIG presented with shift
      concentrations of respirable Cr(VI) below 1 ug m-3. However, very high Cr(VI)
      concentrations may occur, for example in SMAW. The urinary concentration of total
      Cr, cannot be used to precisely determine the shift concentration of respirable
      Cr(VI) in welders.

PMID- 29444200
TI  - Loss of Sirt3 accelerates arterial thrombosis by increasing formation of
      neutrophil extracellular traps and plasma tissue factor activity.
AB  - Aims: Sirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide
      (NAD+)-dependent deacetylase that reduces oxidative stress by activation of
      superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis.
      This study investigated the effects of genetic Sirt3 deletion on arterial
      thrombosis in mice in an inflammatory setting and assessed the clinical relevance
      of these findings in patients with ST-elevation myocardial infarction (STEMI).
      Methods and results: Using a laser-induced carotid thrombosis model with
      lipopolysaccharide (LPS) challenge, in vivo time to thrombotic occlusion in Sirt3
      /- mice (n = 6) was reduced by half compared to Sirt3+/+ wild-type (n = 8, P <
      0.01) controls. Ex vivo analyses of whole blood using rotational
      thromboelastometry revealed accelerated clot formation and increased clot
      stability in Sirt3-/- compared to wild-type blood. rotational thromboelastometry
      of cell-depleted plasma showed accelerated clotting initiation in Sirt3-/- mice,
      whereas overall clot formation and firmness remained unaffected. Ex vivo LPS
      induced neutrophil extracellular trap formation was increased in Sirt3-/- bone
      marrow-derived neutrophils. Plasma tissue factor (TF) levels and activity were
      elevated in Sirt3-/- mice, whereas plasma levels of other coagulation factors and
      TF expression in arterial walls remained unchanged. SOD2 expression in bone
      marrow -derived Sirt3-/- neutrophils was reduced. In STEMI patients,
      transcriptional levels of Sirt3 and its target SOD2 were lower in CD14+
      leukocytes compared with healthy donors (n = 10 each, P < 0.01). Conclusions:
      Sirt3 loss-of-function enhances experimental thrombosis in vivo via an increase
      of neutrophil extracellular traps and elevation of TF suggesting thrombo
      protective effects of endogenous Sirt3. Acute coronary thrombosis in STEMI
      patients is associated with lower expression levels of SIRT3 and SOD2 in CD14+
      leukocytes. Therefore, enhancing SIRT3 activity by pan-sirtuin activating NAD+
      boosters may provide a novel therapeutic target to prevent or treat thrombotic
      arterial occlusion in myocardial infarction or stroke.

PMID- 29444201
TI  - Hierarchical analysis of RNA-seq reads improves the accuracy of allele-specific
      expression.
AB  - Motivation: Allele-specific expression (ASE) refers to the differential abundance
      of the allelic copies of a transcript. RNA sequencing (RNA-seq) can provide
      quantitative estimates of ASE for genes with transcribed polymorphisms. When
      short-read sequences are aligned to a diploid transcriptome, read-mapping
      ambiguities confound our ability to directly count reads. Multi-mapping reads
      aligning equally well to multiple genomic locations, isoforms or alleles can
      comprise the majority (>85%) of reads. Discarding them can result in biases and
      substantial loss of information. Methods have been developed that use weighted
      allocation of read counts but these methods treat the different types of multi
      reads equivalently. We propose a hierarchical approach to allocation of read
      counts that first resolves ambiguities among genes, then among isoforms, and
      lastly between alleles. We have implemented our model in EMASE software
      (Expectation-Maximization for Allele Specific Expression) to estimate total gene
      expression, isoform usage and ASE based on this hierarchical allocation. Results:
      Methods that align RNA-seq reads to a diploid transcriptome incorporating known
      genetic variants improve estimates of ASE and total gene expression compared to
      methods that use reference genome alignments. Weighted allocation methods
      outperform methods that discard multi-reads. Hierarchical allocation of reads
      improves estimation of ASE even when data are simulated from a non-hierarchical
      model. Analysis of RNA-seq data from F1 hybrid mice using EMASE reveals
      widespread ASE associated with cis-acting polymorphisms and a small number of
      parent-of-origin effects. Availability and implementation: EMASE software is
      available at https://github.com/churchill-lab/emase. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29444202
TI  - 'All disease begins in the gut': was Hippocrates right?

PMID- 29444203
TI  - Updated frequency analysis of spinocerebellar ataxia in China.

PMID- 29444204
TI  - Formation of a subero-lignified apical deposit in root tip of radish (Raphanus
      sativus) as a response to copper stress.
AB  - Background and Aims: Heavy metals induce changes in root metabolism and
      physiology, which can lead to a complex remodelling of the root system. The final
      morphological responses of radish (Raphanus sativus) roots exposed to toxic
      concentrations of the heavy metal (Cu) include root growth inhibition,
      differentiation of xylem vessels close to the root tip, enhanced suberin lamellae
      deposition and enhanced lateral root production. Recently, we have found that
      such changes in root morphology and anatomy are coupled to the formation of a
      subero-lignified apical deposit (SLAD) very close to the root tip. Methods: To
      clarify the details of the formation of a SLAD in the root tip, we conducted
      experiments with radish roots exposed to a high Cu concentration (60 um).
      Histochemical analysis of lignin and suberin as well as analysis of spatial
      temporal characteristics of SLAD formation were performed by bright-field,
      fluorescence and confocal microscopy. Key Results: This unique structure, not
      longer than 100 um, consists of modified cell walls of the central cylinder that
      are encircled by a short cylinder of prematurely suberized endodermal cells. A
      SLAD starts to form, in both primary and lateral roots, after cessation of root
      elongation, and it is coupled with xylem differentiation and root branching close
      to the root apex. We noticed that deposition of phenolic substances into a SLAD,
      mainly suberin in the endodermis, is spatially separated from suberization or
      lignification in basally located endodermis. Conclusions: Although the main
      reason for formation of a SLAD is elusive, we suggest that it is a part of stress
      induced responses which relate to decreased root growth or permeability in heavy
      metal stress.

PMID- 29444205
TI  - ssbio: a Python framework for structural systems biology.
AB  - Summary: Working with protein structures at the genome-scale has been challenging
      in a variety of ways. Here, we present ssbio, a Python package that provides a
      framework to easily work with structural information in the context of genome
      scale network reconstructions, which can contain thousands of individual
      proteins. The ssbio package provides an automated pipeline to construct high
      quality genome-scale models with protein structures (GEM-PROs), wrappers to
      popular third-party programs to compute associated protein properties, and
      methods to visualize and annotate structures directly in Jupyter notebooks, thus
      lowering the barrier of linking 3D structural data with established systems
      workflows. Availability and implementation: ssbio is implemented in Python and
      available to download under the MIT license at http://github.com/SBRG/ssbio.
      Documentation and Jupyter notebook tutorials are available at
      http://ssbio.readthedocs.io/en/latest/. Interactive notebooks can be launched
      using Binder at
      https://mybinder.org/v2/gh/SBRG/ssbio/master?filepath=Binder.ipynb. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29444206
TI  - Grimmiaceae in the Early Cretaceous: Tricarinella crassiphylla gen. et sp. nov.
      and the value of anatomically preserved bryophytes.
AB  - Background and Aims: Widespread and diverse in modern ecosystems, mosses are rare
      in the fossil record, especially in pre-Cenozoic rocks. Furthermore, most pre
      Cenozoic mosses are known from compression fossils, which lack detailed
      anatomical information. When preserved, anatomy significantly improves resolution
      in the systematic placement of fossils. Lower Cretaceous (Valanginian) deposits
      on Vancouver Island (British Columbia, Canada) contain a diverse anatomically
      preserved flora including numerous bryophytes, many of which have yet to be
      characterized. Among them is the grimmiaceous moss described here. Methods: One
      fossil moss gametophyte preserved in a carbonate concretion was studied in serial
      sections prepared using the cellulose acetate peel technique. Key Results:
      Tricarinella crassiphylla gen. et sp. nov. is a moss with tristichous phyllotaxis
      and strongly keeled leaves. The combination of an acrocarpous condition (inferred
      based on a series of morphological features), a central conducting strand, a
      homogeneous leaf costa and a lamina with bistratose portions and sinuous cells,
      and multicellular gemmae, supports placement of Tricarinella in family
      Grimmiaceae. Tricarinella is similar to Grimmia, a genus that exhibits broad
      morphological variability. However, tristichous phyllotaxis and especially the
      lamina, bistratose at the base but not in distal portions of the leaf, set
      Tricarinella apart as a distinct genus. Conclusions: Tricarinella crassiphylla
      marks the oldest record for both family Grimmiaceae and sub-class Dicranidae,
      providing a hard minimum age (136 million years) for these groups. The fact that
      this fossil could be placed in an extant family, despite a diminutive size,
      emphasizes the considerable resolving power of anatomically preserved bryophyte
      fossils, even when recovered from allochthonous assemblages of marine sediments,
      such as the Apple Bay flora. Discovery of Tricarinella re-emphasizes the
      importance of paleobotanical studies as the only approach allowing access to a
      significant segment of biodiversity, the extinct biodiversity, which is
      unattainable by other means of investigation.

PMID- 29444193
TI  - Proceedings of the 2017 WAO Symposium on Hot Topics in Allergy: Pediatric &
      Regulatory Aspects: Rome, Italy/Vatican City. 27-29 April 2017.

PMID- 29444207
TI  - The functional network signature of heterogeneity in freezing of gait.
AB  - Freezing of gait is a complex, heterogeneous, and highly variable phenomenon
      whose pathophysiology and neural signature remains enigmatic. Evidence suggests
      that freezing is associated with impairments across cognitive, motor and
      affective domains; however, most research to date has focused on investigating
      one axis of freezing of gait in isolation. This has led to inconsistent findings
      and a range of different pathophysiological models of freezing of gait, due in
      large part to the tendency for studies to investigate freezing of gait as a
      homogeneous entity. To investigate the neural mechanisms of this heterogeneity,
      we used an established virtual reality paradigm to elicit freezing behaviour in
      41 Parkinson's disease patients with freezing of gait and examined individual
      differences in the component processes (i.e. cognitive, motor and affective
      function) that underlie freezing of gait in conjunction with task-based
      functional MRI. First, we combined three unique components of the freezing
      phenotype: impaired set-shifting ability, step time variability, and self
      reported anxiety and depression in a principal components analysis to estimate
      the severity of freezing behaviour with a multivariate approach. By combining
      these measures, we were then able to interrogate the pattern of task-based
      functional connectivity associated with freezing (compared to normal foot
      tapping) in a sub-cohort of 20 participants who experienced sufficient amounts of
      freezing during task functional MRI. Specifically, we used the first principal
      component from our behavioural analysis to classify patterns of functional
      connectivity into those that were associated with: (i) increased severity; (ii)
      increased compensation; or (iii) those that were independent of freezing
      severity. Coupling between the cognitive and limbic networks was associated with
      'worse freezing severity', whereas anti-coupling between the putamen and the
      cognitive and limbic networks was related to 'increased compensation'.
      Additionally, anti-coupling between cognitive cortical regions and the caudate
      nucleus were 'independent of freezing severity' and thus may represent common
      neural underpinnings of freezing that are unaffected by heterogenous factors.
      Finally, we related these connectivity patterns to each of the individual
      components (cognitive, motor, affective) in turn, thus exposing latent
      heterogeneity in the freezing phenotype, while also identifying critical
      functional network signatures that may represent potential targets for novel
      therapeutic intervention. In conclusion, our findings provide confirmatory
      evidence for systems-level impairments in the pathophysiology of freezing of gait
      and further advance our understanding of the whole-brain deficits that mediate
      symptom expression in Parkinson's disease.

PMID- 29444208
TI  - Death on demand? An analysis of physician-administered euthanasia in The
      Netherlands.
AB  - Background: Physician-administered euthanasia (PAE) was legalized, along with
      physician-assisted suicide (PAS), in The Netherlands in 2001. Sources of data:
      Annual reports of the Dutch Regional Euthanasia Review Committees, the
      committees' 2015 published Code of Practice and research studies. Areas of
      agreement: There is a general openness about the practice of PAE/PAS in The
      Netherlands and an avoidance of misleading euphemisms. The 2001 law also includes
      arrangements for post-event review of PAE/PAS decisions. Areas of controversy:
      Rising numbers of annually reported deaths from PAE and uncertainty over actual
      numbers. Movement away from the principle that euthanasia must take place within
      an established doctor-patient relationship. Increasing extension of the 2001 law
      to people with mental health conditions, dementia and multiple co-morbidities.
      Nature of the post-event scrutiny applied to reported cases. Growing points: The
      predominance of PAE over PAS where both are legalized raises questions over how
      these two acts are perceived and whether there are implications for such laws.
      Areas for timely research: Are the criteria for PAE/PAS in the 2001 law
      appropriate for a law of this nature? What should be the respective roles of the
      second-opinion doctors and the review committees?

PMID- 29444209
TI  - Geranylgeranyl pyrophosphate synthase facilitates the organization of
      cardiomyocytes during mid-gestation through modulating protein
      geranylgeranylation in mouse heart.
AB  - Aims: With the maturation of placenta, ventricular chamber maturation enhances
      cardiac contractile performance to adapt to the metabolic demand of growing
      embryo. The organization of cardiomyocytes is required for the morphological
      remodelling in ventricular chamber maturation. However, the mechanism governing
      the establishment of cardiac cytoarchitecture during ventricular chamber
      maturation is still poorly studied. Methods and results: Here, we found that the
      expression of geranylgeranyl pyrophosphate synthase (Ggpps), which mediates
      protein geranylgeranylation, increased in the mouse heart after the onset of
      placental function. By using different Cre lines, we found that the cardiac
      inactivation of Ggpps by the Nkx2.5Cre/+ line disrupted protein
      geranylgeranylation as early as E9.5, which affected ventricular chamber
      maturation and resulted in mid-gestational embryonic lethality. In contrast,
      alpha-SMA-Cre line mediated the disruption of protein geranylgeranylation from
      E13.5 did not affect embryonic heart development. Further analysis of
      Nkx2.5Cre/+; Ggppsfl/fl mutants showed that the loss of Ggpps caused disorganized
      cardiac cytoarchitecture as early as E11.5 by disturbing cell-cell junctions.
      Ggpps inactivation decreased Rho GTPase geranylgeranylation and their activity,
      which might account for the disruption of cell-cell junctions. Moreover,
      elevating the protein geranylgeranylation by supplement of geranylgeranyl
      pyrophosphate (GGPP) could recover the Ggpps deficient induced defects of
      cytoarchitecture and cell-cell junctions in vitro and in vivo. Conclusion: Our
      present study demonstrates that GGPPS-mediated protein geranylgeranylation plays
      an indispensable role in the ventricular chamber maturation and acts as a stage
      specific signal to regulate the establishment of cardiac cytoarchitecture during
      mid-gestation.

PMID- 29444210
TI  - The recurrent mutation in TMEM106B also causes hypomyelinating leukodystrophy in
      China and is a CpG hotspot.

PMID- 29444211
TI  - Optimized protocol of RBCs lysis for immunophenotypic analysis in the peripheral
      blood of tree shrew.

PMID- 29444212
TI  - Loss of function mutations in EPHB4 are responsible for vein of Galen aneurysmal
      malformation.
AB  - See Meschia (doi:10.1093/brain/awy066) for a scientific commentary on this
      article.Vein of Galen aneurysmal malformation is a congenital anomaly of the
      cerebral vasculature representing 30% of all paediatric vascular malformations.
      We conducted whole exome sequencing in 19 unrelated patients presenting this
      malformation and subsequently screened candidate genes in a cohort of 32
      additional patients using either targeted exome or Sanger sequencing. In a cohort
      of 51 patients, we found five affected individuals with heterozygous mutations in
      EPHB4 including de novo frameshift (p.His191Alafs*32) or inherited deleterious
      splice or missense mutations predicted to be pathogenic by in silico tools.
      Knockdown of ephb4 in zebrafish embryos leads to specific anomalies of dorsal
      cranial vessels including the dorsal longitudinal vein, which is the orthologue
      of the median prosencephalic vein and the embryonic precursor of the vein of
      Galen. This model allowed us to investigate EPHB4 loss-of-function mutations in
      this disease by the ability to rescue the brain vascular defect in knockdown
      zebrafish co-injected with wild-type, but not truncated EPHB4, mimicking the
      p.His191Alafs mutation. Our data showed that in both species, loss of function
      mutations of EPHB4 result in specific and similar brain vascular development
      anomalies. Recently, EPHB4 germline mutations have been reported in non-immune
      hydrops fetalis and in cutaneous capillary malformation-arteriovenous
      malformation. Here, we show that EPHB4 mutations are also responsible for vein of
      Galen aneurysmal malformation, indicating that heterozygous germline mutations of
      EPHB4 result in a large clinical spectrum. The identification of EPHB4 pathogenic
      mutations in patients presenting capillary malformation or vein of Galen
      aneurysmal malformation should lead to careful follow-up of pregnancy of carriers
      for early detection of anomaly of the cerebral vasculature in order to propose
      optimal neonatal care. Endovascular embolization indeed greatly improved the
      prognosis of patients.

PMID- 29444213
TI  - Systematic review: methodological flaws in racial/ethnic reporting for
      gastroesophageal reflux disease.
AB  - Health care disparities affecting the care of multiple disease groups are of
      growing concern internationally. Research guidelines, governmental institutions,
      and scientific journals have attempted to minimize disparities through policies
      regarding the collection and reporting of racial/ethnic data. One area where
      shortcomings remain is in gastroesophageal reflux disease (GERD). This systematic
      review, which adheres to the PRISMA statement, focuses on characterizing existing
      methodological weaknesses in research focusing on studies regarding the
      assessment, prevalence, treatment, and outcomes of GERD patients. Search terms
      included GERD and typical symptoms of GERD in ethnic groups or minorities. We
      reviewed 62 articles. The majority of studies did not report the race/ethnicity
      of all participants, and among those who did, very few followed accepted
      guidelines. While there were diverse participants, there was also diversity in
      the manner in which groups were labeled, making comparisons difficult. There
      appeared to be a disparity with respect to countries reporting race/ethnicity,
      with certain countries more likely to report this variable. Samples
      overwhelmingly consisted of the study country's majority population. The majority
      of studies justified the use of race/ethnicity as a study variable and
      investigated conceptually related factors such as socioeconomic status and
      environment. Yet, many studies wrote as if race/ethnicity reflected biological
      differences. Despite recommendations, it appears that GERD researchers around the
      world struggle with the appropriate and standard way to include, collect, report,
      and discuss race/ethnicity. Recommendations on ways to address these issues are
      included with the goal of preventing and identifying health care disparities.

PMID- 29444214
TI  - Minimally invasive esophagectomy may contribute to long-term respiratory function
      after esophagectomy for esophageal cancer.
AB  - Evidence suggests that minimally invasive esophagectomy has several advantages
      with regard to short-term outcomes, compared to open esophagectomy in esophageal
      cancer patients. However, the impact of minimally invasive esophagectomy on long
      term respiratory function remains unknown. The objective of this study is to
      assess the association between use of the minimally invasive esophagectomy and
      long-term respiratory dysfunction in esophageal cancer patients after
      esophagectomy. This retrospective single institution study using prospectively
      collected data included 87 consecutive esophageal cancer patients who had
      undergone esophagectomy. All patients underwent a respiratory function test
      before, and one year after esophagectomy. Logistic regression analysis was used
      to compute the hazard ratio for long-term respiratory dysfunction. Minimally
      invasive esophagectomies were performed in 53 patients, and open esophagectomies
      in 34 patients. The two groups showed no significant differences in terms of
      postoperative complications and postoperative course. Nor were any differences
      observed between the two groups in terms of volume capacity (L) and forced
      expiratory volume 1.0 (L) before esophagectomy (P > 0.34). However, one year
      after esophagectomy, the decreases in volume capacity and forced expiratory
      volume 1.0 were significantly less in the minimally invasive esophagectomy group
      than in the open esophagectomy group (P = 0.04 and P = 0.007, respectively).
      Multivariate analyses revealed that minimally invasive esophagectomy was an
      independent favorable factor for maintenance of forced expiratory volume 1.0
      (hazard ratio = 0.17, 95% confidence interval 0.04-0.71; P = 0.01). Minimally
      invasive esophagectomy may be an independent favorable factor for maintenance of
      long-term respiratory function in esophageal cancer patients after esophagectomy.

PMID- 29444215
TI  - Long-term outcomes of laparoscopic large hiatus hernia repair with nonabsorbable
      mesh.
AB  - The use of mesh to augment suture repair of large hiatus hernias remains
      controversial. Repair with mesh may help reduce the recurrence rate of primary
      repair, but concerns about the potential for serious complications, such as mesh
      erosion or stricturing, continue to limit its use. We aim to evaluate the long
      term outcome of primary hiatus hernia repair with lightweight polypropylene mesh
      (TiMesh) specifically looking at rates of clinical recurrence, dysphagia, and
      mesh-related complications. From a prospectively maintained database, 50
      consecutive patients who underwent elective primary laparoscopic hiatal hernia
      repair with TiMesh between January 2005 and December 2007 were identified. Case
      notes and postoperative endoscopy reports were reviewed. Clinical outcomes were
      evaluated using a structured questionnaire, including a validated dysphagia
      score. Of the 50 patients identified, 36 (72%) were contactable for follow-up. At
      a median follow-up of 9 years, the majority of patients (97%) regarded their
      surgery as successful. Twelve patients (33%) reported a recurrence of their
      symptoms, but only 4 (11%) reported that their symptoms were as severe as prior
      to the surgery. There was no significant difference between pre- and
      postoperative dysphagia scores. Postoperative endoscopy reports were available
      for 32 patients at a median time point of 4 years postoperatively, none of which
      revealed any mesh-related complications. One patient had undergone a revision
      procedure for a recurrent hernia at another institution. In this series, primary
      repair of large hiatus hernia with nonabsorbable mesh was not associated with any
      adverse effects over time. Patient satisfaction with symptomatic outcome remained
      high in the long term.

PMID- 29444216
TI  - Long-term outcomes of single-ventricle palliation for pulmonary atresia with
      intact ventricular septum: Fontan survivors remain at risk of late myocardial
      ischaemia and death.
AB  - OBJECTIVES: The specific outcomes of patients with pulmonary atresia with intact
      ventricular septum late after Fontan palliation are unknown. Patients with
      smaller right ventricles and myocardial sinusoids are known to have worse
      survival in the first years of life. Whether the potential for coronary ischaemia
      affects the long-term outcomes of these patients after Fontan palliation is still
      unknown. METHODS: All patients with pulmonary atresia with intact ventricular
      septum who underwent the Fontan procedure from 1984 to 2016 in Australia and New
      Zealand were identified, and preoperative, perioperative and follow-up data were
      collected. RESULTS: Late follow-up data were available for 120 patients. The
      median length of follow-up after the Fontan procedure was 9.1 years
      (interquartile range 4.2-15.4 years). Late death occurred in 9% of patients
      (11/120). Six were sudden, unexpected deaths; 4 of those occurred in patients
      known to have right ventricle-dependent coronary circulation (RVDCC). Those with
      RVDCC had a higher incidence of sudden death (4/20 vs 2/100; P = 0.007). RVDCC
      was associated with late death (P = 0.01) and the development of myocardial
      ischaemia after Fontan completion (P < 0.001). The 10-year survival rate was 77%
      (95% confidence interval 56-100%) for patients with RVDCC vs 96% (95% confidence
      interval 92-100%) for patients without RVDCC. CONCLUSIONS: Long-term survival of
      patients with pulmonary atresia with intact ventricular septum after the Fontan
      procedure is excellent, but patients with RVDCC remain susceptible to coronary
      ischaemia and sudden death. Closer surveillance and investigation for exercise
      induced ischaemia may be necessary.

PMID- 29444217
TI  - Reply: Updated frequency analysis of spinocerebellar ataxia in China.

PMID- 29444218
TI  - Genomic and physiological characterization and description of Marinobacter
      gelidimuriae sp. nov., a psychrophilic, moderate halophile from Blood Falls, an
      antarctic subglacial brine.
AB  - Antarctic subice environments are diverse, underexplored microbial habitats.
      Here, we describe the ecophysiology and annotated genome of a Marinobacter strain
      isolated from a cold, saline, iron-rich subglacial outflow of the Taylor Glacier,
      Antarctica. This strain (BF04_CF4) grows fastest at neutral pH (range 6-10), is
      psychrophilic (range: 0 degrees C-20 degrees C), moderately halophilic (range:
      0.8%-15% NaCl) and hosts genes encoding potential low temperature and high salt
      adaptations. The predicted proteome suggests it utilizes fewer charged amino
      acids than a mesophilic Marinobacter strain. BF04_CF4 has increased
      concentrations of membrane unsaturated fatty acids including palmitoleic (33%)
      and oleic (27.5%) acids that may help maintain cell membrane fluidity at low
      temperatures. The genome encodes proteins for compatible solute biosynthesis and
      transport, which are known to be important for growth in saline environments.
      Physiological verification of predicted metabolic functions demonstrate BF04_CF4
      is capable of denitrification and may facilitate iron oxidation. Our data
      indicate that strain BF04_CF4 represents a new Marinobacter species, Marinobacter
      gelidimuriae sp. nov., that appears well suited for the subglacial environment it
      was isolated from. Marinobacter species have been isolated from other cold,
      saline environments in the McMurdo Dry Valleys and permanently cold environments
      globally suggesting that this lineage is cosmopolitan and ecologically relevant
      in icy brines.

PMID- 29444219
TI  - Complex cases of acquired pulmonary vein stenosis after radiofrequency ablation:
      is surgical repair an option?
AB  - Aims: Results of catheter based interventional treatment for pulmonary vein
      stenosis (PVS) following radiofrequency ablation (RFA) for atrial fibrillation
      remain suboptimal. Surgical repair may represent an alternative therapy, though
      long-term results have not been thoroughly investigated. Methods and results: We
      retrospectively assessed all patients in our centre undergoing surgical repair
      for radiofrequency-induced PVS. Data regarding surgical technique, clinical
      outcome, and rate of pulmonary vein (PV) restenosis were collected and analysed.
      Between 2004 and 2016, the rate for PVS resulting from RFA for atrial
      fibrillation in our institution was 0.79% (76/9633). During this period, five
      male patients with multiple PVS (3 +/- 1) underwent surgical repair of a total of
      13 symptomatic PVS. Surgery was performed in a standard setting under
      cardiopulmonary bypass. Stenotic veins were incised longitudinally followed by a
      patch augmentation plasty using either bovine pericard (n = 7) or
      polytetrafluoroethylene (PTFE) patches (n = 5). Localization of incision was on
      the anterior side of the PV only (n = 8) or on both the anterior and posterior
      sides (n = 4). In one PVS lesion, mechanical dilatation was sufficient. Long-term
      follow-up after 60 +/- 69 months revealed an average restenosis rate of 38%.
      Restenosis was defined as narrowing >70%. All patients reported clinical
      improvement of symptoms at follow-up. Conclusion: Even in the era of wide
      circumferential lesions, PVS still occurs. While surgical PV patch plasty
      represents a valuable treatment option, restenosis remains an issue during follow
      up. Nevertheless, surgical repair achieves highly acceptable long-term results
      for RFA-acquired PVS. Hence, it should be routinely discussed as a therapeutic
      option in cases with multiple PVS.

PMID- 29444220
TI  - Trends in small-for-gestational age before and after the economic crisis in
      Spain.
AB  - The aim of this study was to evaluate trends in small-for-gestational age
      covering the period before and after the Spanish economic crisis, taking into
      account mother's age, nationality and the autonomous community where she resides.
      We performed a trend study including children born to fertile women in Spain
      between 2002 and 2013. Poisson mixed models showed that the prevalence of small
      for-gestational age increased following the onset of the crisis, and that a
      previous downward trend was interrupted.

PMID- 29444221
TI  - Split P waves: marker of extreme interatrial delay.

PMID- 29444222
TI  - Extracorporeal membrane oxygenation as a bridge to lung transplantation may not
      impact overall mortality risk after transplantation: results from a 7-year single
      centre experience.
AB  - OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has an important role in
      bridging patients to lung transplantation. In this study, we present our
      experience with pretransplant ECMO during the last 7 years and investigate its
      impact on graft outcomes. METHODS: Records of all lung-transplanted patients at
      our institution between January 2010 and April 2017 were retrospectively
      reviewed. Graft survival was compared between patients who required pretransplant
      ECMO (pre-Tx ECMO+) and patients who did not (pre-Tx ECMO-). Risk factors for in
      hospital mortality and graft survival were identified using a binary logistic
      regression and the Cox regression analyses, respectively. RESULTS: Among the 917
      patients transplanted during the study period, 68 (7%) required ECMO as a bridge
      to transplantation [awake strategy, n = 57 (84%) patients]. Median bridging time
      was 9 days. Among pre-Tx ECMO+ patients, the need for haemodialysis at any point
      during bridging emerged as an independent risk factor for in-hospital mortality
      (odds ratio 7.79, 95% confidence interval 1.21-50.24; P = 0.031). Although in
      hospital mortality was significantly higher in pre-Tx ECMO+ versus pre-Tx ECMO-
      patients (15% vs 5%, P = 0.003), overall graft survival did not differ between
      groups (79% vs 90% and 61% vs 68% at 1 and 5 years, respectively, P = 0.13).
      Pretransplant ECMO did not emerge as a risk factor for graft survival in the
      multivariable analysis. CONCLUSIONS: If applied in selected patients in a high
      volume centre, pretransplant ECMO as a bridge to transplantation results in
      impaired, but still high in-hospital, survival and does not impact graft
      survival.

PMID- 29444224
TI  - A systematic review with meta-analysis of the prevalence of gastroesophageal
      reflux in congenital diaphragmatic hernia pediatric survivors.
AB  - Congenital diaphragmatic hernia survivors are a well-known group at risk for
      developing gastroesophageal reflux disease that may be particularly long-term
      severe. The aim of this study is to provide a systematic review of the prevalence
      of gastroesophageal reflux in infant and children survivors treated for
      congenital diaphragmatic hernia.Electronic and manual searches were performed
      with keywords related to congenital diaphragmatic hernia, gastroesophageal reflux
      disease, and epidemiology terms. Summary estimates of the prevalence were
      calculated. Effect model was chosen depending on heterogeneity (I2). Factors
      potentially related with the prevalence, including study quality or the
      diagnostic strategy followed, were assessed by subgroup and meta-regression
      analyses. Risk of publication bias was studied by funnel plot analysis and the
      Egger test.The search yielded 140 articles, 26 of which were included in the
      analyses and provided 34 estimates of prevalence: 21 in patients aged 12 months
      or younger, and 13 in older children. The overall prevalence of gastroesophageal
      reflux disease in infants was 52.7% (95% confidence interval [CI]: 43.2% to
      62.1%, I2 = 88.7%) and, in children over 1 year old, 35.1% (95% CI: 25.4% to
      45.3%, I2 = 73.5%). Significant clinical and statistical heterogeneity was found.
      The strategy chosen for gastroesophageal reflux diagnosis influenced the reported
      prevalence. The only estimate obtained with a systematic use of multichannel
      intraluminal impedance provided a higher prevalence in both age groups: 83.3%
      (95% CI: 67.2% to 93.6%) and 61.1% (95% CI: 43.5% to 76.9%) respectively. This
      last prevalence did not significantly differ from that obtained using only low
      risk of bias estimates.As a conclusion, gastroesophageal reflux disease is
      commonly observed after congenital diaphragmatic hernia repair and is almost
      constantly present in the first months of life. It may be underdiagnosed if
      systematically esophageal monitoring is not performed. This should be considered
      when proposing follow-up and management protocols for congenital diaphragmatic
      hernia survivors.

PMID- 29444223
TI  - GLP-1 Receptor Expression Within the Human Heart.
AB  - Glucagonlike peptide-1 receptor (GLP-1R) agonists, which are used to treat type 2
      diabetes and obesity, reduce the rates of myocardial infarction and
      cardiovascular death. GLP-1R has been localized to the human sinoatrial node;
      however, its expression in ventricular tissue remains uncertain. Here we studied
      GLP-1R expression in the human heart using GLP-1R-directed antisera, quantitative
      polymerase chain reaction (PCR), reverse transcription PCR to detect full-length
      messenger RNA (mRNA) transcripts, and in situ hybridization (ISH). GLP1R mRNA
      transcripts, encompassing the entire open reading frame, were detected in all
      four cardiac chambers from 15 hearts at levels approximating those detected in
      human pancreas. In contrast, cardiac GLP2R expression was relatively lower, and
      cardiac GCGR expression was sporadic and not detected in the left ventricle.
      GLP1R mRNA transcripts were not detected in RNA from human cardiac fibroblasts,
      coronary artery endothelial, or vascular smooth muscle cells. Human Brunner
      glands and pancreatic islets exhibited GLP-1R immunopositivity and abundant
      expression of GLP1R mRNA transcripts by ISH. GLP1R transcripts were also detected
      by ISH in human cardiac sinoatrial node tissue. However, definitive cellular
      localization of GLP1R mRNA transcripts or immunoreactive GLP-1R protein within
      human cardiomyocytes or cardiac blood vessels remained elusive. Moreover,
      validated GLP-1R antisera lacked sufficient sensitivity to detect expression of
      the endogenous islet or cardiac GLP-1R by Western blotting. Hence, although human
      cardiac ventricles express the GLP1R, the identity of one or more ventricular
      cell type(s) that express a translated GLP1R protein requires further
      clarification with highly sensitive methods of detection.

PMID- 29444226
TI  - Benfluorex-induced severe primary tricuspid and mitral regurgitation requiring a
      double-valve replacement.

PMID- 29444225
TI  - Association of Neighborhood Socioeconomic Status With Risk of Infection and
      Sepsis.
AB  - Background: Prior studies suggest disparities in sepsis risk and outcomes based
      on place of residence. We sought to examine the association between neighborhood
      socioeconomic status (nSES) and hospitalization for infection and sepsis.
      Methods: We conducted a prospective cohort study using data from 30239
      participants in the Reasons for Geographic and Racial Differences in Stroke
      (REGARDS) study. nSES was defined using a score derived from census data and
      classified into quartiles. Infection and sepsis hospitalizations were identified
      over the period 2003-2012. We fit Cox proportional hazards models, reporting
      hazard ratios (HRs) with 95% confidence intervals (CIs) and examining mediation
      by participant characteristics. Results: Over a median follow-up of 6.5 years,
      there were 3054 hospitalizations for serious infection. Infection incidence was
      lower for participants in the highest nSES quartile compared with the lowest
      quartile (11.7 vs 15.6 per 1000 person-years). After adjustment for demographics,
      comorbidities, and functional status, infection hazards were also lower for the
      highest quartile (HR, 0.84 [95% CI, .73-.97]), with a linear trend (P = .011).
      However, there was no association between nSES and sepsis at presentation among
      those hospitalized with infection. Physical weakness, income, and diabetes had
      modest mediating effects on the association of nSES with infection. Conclusions:
      Our study shows that differential infection risk may explain nSES disparities in
      sepsis incidence, as higher nSES is associated with lower infection
      hospitalization rates, but there is no association with sepsis among those
      hospitalized. Mediation analysis showed that nSES may influence infection
      hospitalization risk at least partially through physical weakness, individual
      income, and comorbid diabetes.

PMID- 29444227
TI  - The Ross-Konno procedure in neonates and infants less than 3 months of age.
AB  - OBJECTIVES: Patients with severe left ventricular outflow tract obstruction often
      suffer from impaired left ventricular function, endocardial fibroelastosis and
      borderline-sized structures. The early Ross-Konno operation can offer complete
      repair due to outflow tract stenosis and enable the functional recovery and
      growth of small structures. METHODS: Between 2008 and March 2017, 44 early Ross
      Konno procedures were performed at our centre. Thirty-five patients were
      neonates, and 9 were infants less than 3 months of age. A retrospective single
      centre investigation was carried out analysing early and late deaths,
      postoperative complications and reoperations during the follow-up period.
      Potential prognostic influence factors as previous fetal intervention, associated
      lesions as presence of a VSD or hypoplastic aortic arch or severe endocardial
      fibroelastosis were examined. RESULTS: The in-hospital mortality rate was 7% (3
      of 44), and the late mortality rate was 2%. There were no deaths in the group
      with ventricular septal defects (9 cases), and there was 1 death in the group
      with critical aortic stenosis without arch repair (1 of 24; 4%). The most deaths
      occurred in patients with critical aortic stenosis and aortic arch repair (3 of
      11; 27%) (P = 0.012). Fifteen patients with foetal intervention had a mid-term
      survival rate of 87%. Reoperations were necessary in 19 of 40 surviving patients
      during a mean follow-up period of 5.9 years. CONCLUSIONS: The early Ross-Konno
      procedure can enable biventricular repair even in borderline left ventricles with
      good long-term outcome. Thus far, there were no reoperations at the level of the
      autograft or the left ventricular outflow tract in our cohort. The highest
      operative risk was observed in patients with critical aortic stenosis and aortic
      arch hypoplasia.

PMID- 29444228
TI  - Towards optimal electronic medical record use: perspectives of advanced users.
AB  - Background: While primary health care electronic medical record (EMR) adoption
      has increased in Canada, the use of advanced EMR features is limited. Realizing
      the potential benefits of primary health care EMR use is dependent not only on
      EMR acquisition, but also on its comprehensive use and integration into practice;
      yet, little is known about the advanced use of EMRs in primary health care.
      Objective: To explore the views of advanced primary health care EMR users
      practising in a team-based environment. Methods: A descriptive qualitative
      approach was used to explore the views of primary health care practitioners who
      were identified as advanced EMR users. Twelve individual semi-structured
      interviews were held with primary health care practitioners in Southwestern
      Ontario, Canada. Field notes were created after each interview. Interviews were
      audio recorded and transcribed verbatim. Researchers independently coded the
      transcripts and then met to discuss the results of the coding. We used a thematic
      approach to data analysis. Results: Three themes emerged from the data analysis:
      advanced EMR users as individuals with signature characteristics, advanced EMR
      users as visionaries and advanced EMR users as agents of change. In any one
      participant, these elements could overlap, illuminating the important interplay
      between these themes. Taken together, these themes defined advanced use among
      this group of primary health care practitioners. Conclusions: To realize the
      potential benefits of EMR use in improved patient care and outcomes, we need to
      understand how to support EMR use. This study provides a necessary building block
      in furthering this understanding.

PMID- 29444229
TI  - Bioprosthetic mitral valve replacement in patients aged 65 years or younger: long
      term outcomes with the Carpentier-Edwards PERIMOUNT pericardial valve.
AB  - OBJECTIVES: Mitral valve replacement using a bioprosthesis remains controversial
      in young patients because data on long-term outcomes are missing. This study
      evaluated the long-term results of the PERIMOUNT pericardial mitral bioprosthesis
      in patients aged 65 years or younger. METHODS: From 1984 to 2010, 148 Carpentier
      Edwards PERIMOUNT mitral bioprostheses were implanted in 148 patients aged 65
      years or younger. Baseline clinical, perioperative and follow-up data were
      recorded prospectively. Structural valve deterioration (SVD) was defined by
      strict echocardiographic assessment. RESULTS: The mean follow-up period was 8.6
      +/- 5.5 years, for a total of 1269 valve-years. Operative mortality rate was
      2.0%. Fifty-one late deaths occurred (linearized rate 4.0% per valve-year).
      Actuarial survival rates averaged 70 +/- 4%, 53 +/- 6% and 31 +/- 7% after 10, 15
      and 20 years of follow-up, respectively. Actuarial freedom from SVD at 10, 15 and
      20 years was 78 +/- 5%, 47 +/- 7% and 19 +/- 7%, respectively. Reoperation was
      associated with no operative mortality. Actuarial freedom from reoperation due to
      SVD at 10, 15 and 20 years was 82 +/- 4%, 50 +/- 6% and 25 +/- 8%, respectively.
      Competing risk analysis demonstrated an actual risk of explantation secondary to
      SVD at 20 years of 44 +/- 5%. Expected valve durability was 14.2 years for this
      age group. CONCLUSIONS: In the selected patients aged 65 years or younger
      undergoing mitral valve replacement with a pericardial bioprosthesis, the
      expected valve durability was 14.2 years. Reoperation for SVD was associated with
      a low risk of mortality.

PMID- 29444230
TI  - Social movement involvement and healthy diet and activity behaviors among US
      adults.
AB  - Unhealthy lifestyle behaviors, namely poor diet and inadequate physical activity,
      significantly contribute to poor health and obesity risk, which in turn impact
      chronic illness outcomes. A possible approach to improving these health behaviors
      and subsequent outcomes is to capitalize on the theorized link between social
      movement involvement and overlapping health behaviors. Social movement
      involvement may be a viable stealth intervention for health, utilizing intrinsic
      motivators to improve health without an explicit focus on changing health
      behavior. Thus, the current study explored the links between social movement
      involvement and diet and physical activity. Two samples from a college population
      (N = 196) and the general population (N = 195) participated in an online survey,
      which included measures of social movement involvement, social movement-related
      health behaviors and dietary intake and physical activity. After controlling for
      known covariates, social movement-related health behaviors mediated the
      relationship between level of social movement involvement and fruit and vegetable
      consumption, whole grain intake and average daily physical activity in both
      samples. These findings suggest that health behaviors associated with social
      movement involvement may be an important mechanism in promoting health among
      social movement members and that the model holds across adult populations. This
      research adds to existing literature on stealth interventions as a viable means
      of improving important behavioral health components linked with obesity and
      chronic disease and supports social movement involvement as a potential form of
      stealth intervention.

PMID- 29444231
TI  - Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or
      refractory B-cell non-Hodgkin's lymphoma.
AB  - Background: This two-stage, phase IIa study investigated the antitumor activity
      and safety of MOR208, an Fc-engineered, humanized, CD19 antibody, in patients
      with relapsed or refractory (R-R) B-cell non-Hodgkin's lymphoma (NHL). CD19 is
      broadly expressed across the B-lymphocyte lineage, including in B-cell
      malignancies, but not by hematological stem cells. Patients and methods: Patients
      aged >=18 years, with R-R NHL progressing after >=1 prior rituximab-containing
      regimen were enrolled into subtype-specific cohorts: diffuse large B-cell
      lymphoma (DLBCL), follicular lymphoma (FL), other indolent (i)NHL and mantle cell
      lymphoma (MCL). Treatment was MOR208, 12 mg/kg intravenously, weekly, for 8
      weeks. Patients with at least stable disease could continue treatment for an
      additional 4 weeks. Those with a partial or complete response after 12 weeks
      could receive extended MOR208 treatment (12 mg/kg, either monthly or every second
      week) until progression. The primary end point was overall response rate.
      Results: Ninety-two patients were enrolled: DLBCL (n = 35), FL (n = 34), other
      iNHL (n = 11) and MCL (n = 12). Responses were observed in DLBCL, FL and other
      iNHL cohorts (26%, 29% and 27%, respectively). They lasted >=12 months in 5/9
      responding patients with DLBCL, 4/9 with FL and 2/3 with other iNHL. Responses in
      nine patients are ongoing (>26 months in five instances). Patients with rituximab
      refractory disease showed a similar response rate and progression-free survival
      time to patients with non-refractory disease. The most common adverse events (any
      grade) were infusion-related reactions (12%) and neutropenia (12%). One patient
      experienced a grade 4 infusion-related reaction and eight patients (9%)
      experienced grade 3/4 neutropenia. No treatment-related deaths were reported.
      Conclusions: MOR208 monotherapy demonstrated promising clinical activity in
      patients with R-R DLBCL and R-R FL, including in patients with rituximab
      refractory tumors. These efficacy data and the favorable safety profile support
      further investigation of MOR208 in phase II/III combination therapy trials in R-R
      DLBCL. ClinicalTrials.gov number: NCT01685008.

PMID- 29444232
TI  - HiCapTools: a software suite for probe design and proximity detection for
      targeted chromosome conformation capture applications.
AB  - Summary: Folding of eukaryotic genomes within nuclear space enables physical and
      functional contacts between regions that are otherwise kilobases away in sequence
      space. Targeted chromosome conformation capture methods (T2C, chi-C and HiCap)
      are capable of informing genomic contacts for a subset of regions targeted by
      probes. We here present HiCapTools, a software package that can design sequence
      capture probes for targeted chromosome capture applications and analyse
      sequencing output to detect proximities involving targeted fragments. Two probes
      are designed for each feature while avoiding repeat elements and non-unique
      regions. The data analysis suite processes alignment files to report genomic
      proximities for each feature at restriction fragment level and is isoform-aware
      for gene features. Statistical significance of contact frequencies is evaluated
      using an empirically derived background distribution. Targeted chromosome
      conformation capture applications are invaluable for locating target genes of
      disease-associated variants found by genome-wide association studies. Hence, we
      believe our software suite will prove to be useful for a wider user base within
      clinical and functional applications. Availability:
      https://github.com/sahlenlab/HiCapTools. Contact: pelinak@kth.se. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29444233
TI  - BetaSerpentine: a bioinformatics tool for reconstruction of amyloid structures.
AB  - Motivation: Numerous experimental studies have suggested that polypeptide chains
      of large amyloidogenic regions zig-zag in beta-serpentine arrangements. These
      beta-serpentines are stacked axially and form the superpleated beta-structure.
      Despite this progress in the understanding of amyloid folds, the determination of
      their 3D structure at the atomic level is still a problem due to the polymorphism
      of these fibrils and incompleteness of experimental structural data. Today, the
      way to get insight into the atomic structure of amyloids is a combination of
      experimental studies with bioinformatics. Results: We developed a computer
      program BetaSerpentine that reconstructs beta-serpentine arrangements from
      individual beta-arches predicted by ArchCandy program and ranks them in order of
      preference. It was shown that the BetaSerpentine program in combination with the
      experimental data can be used to gain insight into the detailed 3D structure of
      amyloids. It opens avenues to the structure-based interpretation and design of
      the experiments. Availability and implementation: BetaSerpentine webserver can be
      accessed through website: http://bioinfo.montp.cnrs.fr/b-serpentine. Source code
      is available in git.hub repository (github.com/stanislavspbgu/BetaSerpentine).
      Contact: stanislavspbgu@gmail.com or andrey.kajava@crbm.cnrs.fr. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29444234
TI  - ThreaDNA: predicting DNA mechanics' contribution to sequence selectivity of
      proteins along whole genomes.
AB  - Motivation: Many DNA-binding proteins recognize their target sequences
      indirectly, by sensing DNA's response to mechanical distortion. ThreaDNA
      estimates this response based on high-resolution structures of the protein-DNA
      complex of interest. Implementing an efficient nanoscale modeling of DNA
      deformations involving essentially no adjustable parameters, it returns the
      profile of deformation energy along whole genomes, at base-pair resolution,
      within minutes on usual laptop/desktop computers. Our predictions can also be
      easily combined with estimations of direct selectivity through a generalized form
      of position-weight-matrices. The formalism of ThreaDNA is accessible to a wide
      audience. Results: We demonstrate the importance of indirect readout for the
      nucleosome as well as the bacterial regulators Fis and CRP. Combined with the
      direct contribution provided by usual sequence motifs, it significantly improves
      the prediction of sequence selectivity, and allows quantifying the two distinct
      physical mechanisms underlying it. Availability and implementation: Python
      software available at bioinfo.insa-lyon.fr, natively executable on Linux/MacOS
      systems with a user-friendly graphical interface. Galaxy webserver version
      available. Contact: sam.meyer@insa-lyon.fr. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29444235
TI  - Squeakr: an exact and approximate k-mer counting system.
AB  - Motivation: k-mer-based algorithms have become increasingly popular in the
      processing of high-throughput sequencing data. These algorithms span the gamut of
      the analysis pipeline from k-mer counting (e.g. for estimating assembly
      parameters), to error correction, genome and transcriptome assembly, and even
      transcript quantification. Yet, these tasks often use very different k-mer
      representations and data structures. In this article, we show how to build a k
      mer-counting and multiset-representation system using the counting quotient
      filter, a feature-rich approximate membership query data structure. We introduce
      the k-mer-counting/querying system Squeakr (Simple Quotient filter-based Exact
      and Approximate Kmer Representation), which is based on the counting quotient
      filter. This off-the-shelf data structure turns out to be an efficient
      (approximate or exact) representation for sets or multisets of k-mers. Results:
      Squeakr takes 2*-4.3* less time than the state-of-the-art to count and perform a
      random-point-query workload. Squeakr is memory-efficient, consuming 1.5*-4.3*
      less memory than the state-of-the-art. It offers competitive counting
      performance. In fact, it is faster for larger k-mers, and answers point queries
      (i.e. queries for the abundance of a particular k-mer) over an order-of-magnitude
      faster than other systems. The Squeakr representation of the k-mer multiset turns
      out to be immediately useful for downstream processing (e.g. de Bruijn graph
      traversal) because it supports fast queries and dynamic k-mer insertion,
      deletion, and modification. Availability and implementation:
      https://github.com/splatlab/squeakr available under BSD 3-Clause License.
      Contact: ppandey@cs.stonybrook.edu. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29444236
TI  - findGSE: estimating genome size variation within human and Arabidopsis using k
      mer frequencies.
AB  - Motivation: Analyzing k-mer frequencies in whole-genome sequencing data is
      becoming a common method for estimating genome size (GS). However, it remains
      uninvestigated how accurate the method is, especially if it can capture intra
      species GS variation. Results: We present findGSE, which fits skew normal
      distributions to k-mer frequencies to estimate GS. findGSE outperformed existing
      tools in an extensive simulation study. Estimating GSs of 89 Arabidopsis thaliana
      accessions, findGSE showed the highest capability in capturing GS variations. In
      an application with 71 female and 71 male human individuals, findGSE delivered an
      average of 3039 Mb as haploid human GS, while female genomes were on average 41
      Mb larger than male genomes, in astonishing agreement with size difference of the
      X and Y chromosomes. Further analysis showed that human GS variations link to
      geographical patterns and significant differences between populations, which can
      be explained by variable abundances of LINE-1 retrotransposons. Availability and
      implementation: R package of findGSE is freely available at
      https://github.com/schneebergerlab/findGSE and supported on linux and Mac
      systems. Contact: schneeberger@mpipz.mpg.de. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29444237
TI  - Compression of genomic sequencing reads via hash-based reordering: algorithm and
      analysis.
AB  - Motivation: New Generation Sequencing (NGS) technologies for genome sequencing
      produce large amounts of short genomic reads per experiment, which are highly
      redundant and compressible. However, general-purpose compressors are unable to
      exploit this redundancy due to the special structure present in the data.
      Results: We present a new algorithm for compressing reads both with and without
      preserving the read order. In both cases, it achieves 1.4*-2* compression gain
      over state-of-the-art read compression tools for datasets containing as many as 3
      billion Illumina reads. Our tool is based on the idea of approximately reordering
      the reads according to their position in the genome using hashed substring
      indices. We also present a systematic analysis of the read compression problem
      and compute bounds on fundamental limits of read compression. This analysis sheds
      light on the dynamics of the proposed algorithm (and read compression algorithms
      in general) and helps understand its performance in practice. The algorithm
      compresses only the read sequence, works with unaligned FASTQ files, and does not
      require a reference. Contact: schandak@stanford.edu. Supplementary information:
      Supplementary material are available at Bioinformatics online. The proposed
      algorithm is available for download at https://github.com/shubhamchandak94/HARC.

PMID- 29444238
TI  - Vitamin D receptor restricts T helper 2-biased inflammation in the heart.
AB  - Background and aims: The aberrant immune responses play a critical role in the
      pathogenesis of myocarditis. Vitamin D receptor (VDR) has immune regulatory
      functions. This study aims to investigate the role of VDR in restricting the
      immune inflammation in the heart. Methods and results: The human heart samples
      were obtained from the heart transplantation. T helper (Th)2 and Th1 responses in
      the heart tissue were characterized by histology and immune assay. VDR-/- mice
      and recombination activating gene 2-/- mice were used in the experiments to test
      the role of VDR in maintaining the homeostasis in the heart. The results showed
      that, besides tissue damage, lower expression of VDR, high frequency of Th2 cells
      and increase in Th2 cytokines in the hearts of patients with myocarditis at the
      end stage of heart failure. The spontaneous Th2-biased inflammation was observed
      in the hearts of VDR-/- mice. CD4+ T cells from the VDR-/- mouse hearts were at
      highly activating status. The naive VDR-/- CD4+ T cells and naive CD4+ T cells
      from human hearts with myocarditis were prone to differentiate into Th2 cells.
      VDR formed complexes with GATA3, the interleukin (IL)-4 transcription factor, to
      prevent the Il4 gene transcription. Transplantation with VDR-/-CD4+ T cells
      induced the Th2-biased inflammation in the hearts of Rag2-/- mice. Reconstitution
      of VDR in CD4+ T cells inhibited the Th2-biased inflammation in the heart.
      Conclusions: VDR-deficiency contributes to the pathogenesis of myocarditis. To
      enhance the VDR expression in CD4+, T cells haves the therapeutic potential for
      the treatment of myocarditis.

PMID- 29444239
TI  - Therapeutic efficacy of microtube-embedded chondroitinase ABC in a canine
      clinical model of spinal cord injury.
AB  - See Moon and Bradbury (doi:10.1093/brain/awy067) for a scientific commentary on
      this article.Many hundreds of thousands of people around the world are living
      with the long-term consequences of spinal cord injury and they need effective new
      therapies. Laboratory research in experimental animals has identified a large
      number of potentially translatable interventions but transition to the clinic is
      not straightforward. Further evidence of efficacy in more clinically-relevant
      lesions is required to gain sufficient confidence to commence human clinical
      trials. Of the many therapeutic candidates currently available, intraspinally
      applied chondroitinase ABC has particularly well documented efficacy in
      experimental animals. In this study we measured the effects of this intervention
      in a double-blinded randomized controlled trial in a cohort of dogs with
      naturally-occurring severe chronic spinal cord injuries that model the condition
      in humans. First, we collected baseline data on a series of outcomes: forelimb
      hindlimb coordination (the prespecified primary outcome measure), skin
      sensitivity along the back, somatosensory evoked and transcranial magnetic motor
      evoked potentials and cystometry in 60 dogs with thoracolumbar lesions. Dogs were
      then randomized 1:1 to receive intraspinal injections of heat-stabilized, lipid
      microtube-embedded chondroitinase ABC or sham injections consisting of needle
      puncture of the skin. Outcome data were measured at 1, 3 and 6 months after
      intervention; skin sensitivity was also measured 24 h after injection (or sham).
      Forelimb-hindlimb coordination was affected by neither time nor chondroitinase
      treatment alone but there was a significant interaction between these variables
      such that coordination between forelimb and hindlimb stepping improved during the
      6-month follow-up period in the chondroitinase-treated animals by a mean of 23%,
      but did not change in controls. Three dogs (10%) in the chondroitinase group also
      recovered the ability to ambulate without assistance. Sensitivity of the dorsal
      skin increased at 24 h after intervention in both groups but subsequently
      decreased to normal levels. Cystometry identified a non-significant improvement
      of bladder compliance at 1 month in the chondroitinase-injected dogs but this did
      not persist. There were no overall differences between groups in detection of
      sensory evoked potentials. Our results strongly support a beneficial effect of
      intraspinal injection of chondroitinase ABC on spinal cord function in this
      highly clinically-relevant model of chronic severe spinal cord injury. There was
      no evidence of long-term adverse effects associated with this intervention. We
      therefore conclude that this study provides strong evidence in support of
      initiation of clinical trials of chondroitinase ABC in humans with chronic spinal
      cord injury.

PMID- 29444240
TI  - Isolation and Characterization of Novel Polymorphic Microsatellite Markers for
      Cimex hemipterus F. (Hemiptera: Cimicidae).
AB  - Due to the growing public health and tourism awareness, Cimex hemipterus
      Fabricius (Hemiptera: Cimicidae) has gained a great interest in increasing
      reported infestation cases in tropical regions of the world, including Malaysia.
      Since the information on the molecular ecology and population biology of this
      species are tremendously lacking, the isolation and development of molecular
      markers can be used to determine its genetic structure. In this study, novel
      microsatellite primers isolated from enriched genomic libraries of C. hemipterus
      were developed using 454 Roche shotgun sequencing. Seven validated polymorphic
      microsatellite primers were consistently amplified and characterized from 70
      tropical bed bugs collected from seven locations throughout Malaysia. The number
      of alleles per locus identified ranged from 6 to 14. Comparison of loci for
      overall and between population were done with mean observed and expected
      heterozygosity were determined at 0.320 and 0.814, 0.320 and 0.727, respectively.
      Polymorphic information criteria (PIC) valued the markers as highly informative
      as PIC >0.5. Overall population, they are possibly in Hardy-Weinberg equilibrium
      with loci Ch_09ttn, Ch_01dn, and Ch_13dn showing signs of a null allele. There
      were no scoring errors caused by stutter peaks, no large allele dropout was
      detected for all loci and showed no evidence of linkage disequilibrium. In
      conclusion, all seven molecular microsatellite markers identified can be
      beneficially used to gain more information on the population genetic structure
      and breeding patterns of C. hemipterus as well as the relationship of dispersal
      and infestation.

PMID- 29444241
TI  - Macro-environmental factors and physical activity in 28 European Union countries.
AB  - Data from the representative 2013 Eurobarometer survey were combined with macro
      environmental data to assess relationships with different domains of physical
      activity (PA) in 28 European Union countries. Higher mean annual temperatures
      were the only macro-environmental factor found to be associated with levels of
      physical activity; an increase in the mean annual temperature by 1 degrees C was
      associated with-0.94 fewer minutes of vigorous-intensity activity per week (95%
      CI: -1.66 to -0.23). This highlights the importance of modifiable influences
      (e.g. opportunities for active travel) on PA and underscores the potential of
      public health interventions to raise levels of physical activity.

PMID- 29444242
TI  - In vitro activity of zoliflodacin (ETX0914) against macrolide-resistant,
      fluoroquinolone-resistant and antimicrobial-susceptible Mycoplasma genitalium
      strains.
AB  - Background: Mycoplasma genitalium is estimated to be the second most common cause
      of bacterial sexually transmitted infection in Europe. It is of increasing public
      health concern due to the rapid development of resistance to different
      antimicrobial classes, including the preferred first- and second-line treatments
      azithromycin and moxifloxacin. Thus, new antimicrobial agents are urgently
      needed, especially for the treatment of MDR strains. Methods: The in vitro
      activity of the new spiropyrimidinetrione zoliflodacin against 47 M. genitalium
      strains was assessed by growing M. genitalium in Vero cell culture and measuring
      growth by quantitative PCR. The collection included 34 moxifloxacin-susceptible
      (MIC <1 mg/L) and 13 moxifloxacin-resistant (MIC >=1 mg/L) strains. Twenty-three
      of the strains were azithromycin resistant (MIC >=16 mg/L) and 12 of these
      strains were MDR. Results: Only one (2.1%) strain with substantially increased
      MIC (4 mg/L) and potential resistance to zoliflodacin was found. Zoliflodacin was
      overall more potent than moxifloxacin (P = 0.009) and no cross-resistance was
      observed between the two drug classes of topoisomerase II inhibitors. Differences
      in the MICs of zoliflodacin and azithromycin were not statistically significant;
      however, 23 (48.9%) compared with potentially 1 (2.1%) of the strains were
      resistant to azithromycin and zoliflodacin, respectively. Conclusions:
      Zoliflodacin is a promising candidate for the treatment of M. genitalium and it
      is important to further develop and evaluate this drug.

PMID- 29444243
TI  - Implementing pharmacogenomics decision support across seven European countries:
      The Ubiquitous Pharmacogenomics (U-PGx) project.
AB  - Clinical pharmacogenomics (PGx) has the potential to make pharmacotherapy safer
      and more effective by utilizing genetic patient data for drug dosing and
      selection. However, widespread adoption of PGx depends on its successful
      integration into routine clinical care through clinical decision support tools,
      which is often hampered by insufficient or fragmented infrastructures. This paper
      describes the setup and implementation of a unique multimodal, multilingual
      clinical decision support intervention consisting of digital, paper-, and mobile
      based tools that are deployed across implementation sites in seven European
      countries participating in the Ubiquitous PGx (U-PGx) project.

PMID- 29444244
TI  - Acute Toxicity of Permethrin, Deltamethrin, and Etofenprox to the Alfalfa
      Leafcutting Bee.
AB  - Current regulatory requirements for insecticide toxicity to nontarget insects
      focus on the honey bee, Apis mellifera (L.; Hymenoptera: Apidae), but this
      species cannot represent all insect pollinator species in terms of response to
      insecticides. Therefore, we characterized the toxicity of pyrethroid insecticides
      used for adult mosquito management (permethrin, deltamethrin, and etofenprox) on
      a nontarget insect, the adult alfalfa leafcutting bee, Megachile rotundata (F.;
      Hymenoptera: Megachilidae) in two separate studies. In the first study, the doses
      causing 50 and 90% mortality (LD50 and LD90, respectively) were used as endpoints
      and 2-d-old adult females were exposed to eight concentrations ranging from
      0.0075 to 0.076 MUg/bee for permethrin and etofenprox, and 0.0013-0.0075 MUg/bee
      for deltamethrin. For the second study, respiration rates of female M. rotundata
      were also recorded for 2 h after bees were dosed at the LD50 values to give an
      indication of stress response. Results indicated a relatively similar LD50 for
      permethrin and etofenprox, 0.057 and 0.051 MUg/bee, respectively, and a more
      toxic response, 0.0016 MUg/bee for deltamethrin. Comparatively, female A.
      mellifera workers have a LD50 value of 0.024 MUg/bee for permethrin and 0.015
      MUg/bee for etofenprox indicating that female M. rotundata are less susceptible
      to topical doses of these insecticides, except for deltamethrin, where both A.
      mellifera and M. rotundata have an identical LD50 of 0.0016 MUg/bee. Respiration
      rates comparing each active ingredient to control groups, as well as rates
      between each active ingredient, were statistically different (P < 0.0001). The
      addition of these results to existing information on A. mellifera may provide
      more insights on how other economically beneficial and nontarget bees respond to
      pyrethroids.

PMID- 29444245
TI  - mcr-5 and a novel mcr-5.2 variant in Escherichia coli isolates from food and food
      producing animals, Germany, 2010 to 2017.

PMID- 29444246
TI  - Reply: The recurrent mutation in TMEM106B also causes hypomyelinating
      leukodystrophy in China and is a CpG hotspot.

PMID- 29444247
TI  - Infectious Diseases Physicians: Leading the Way in Antimicrobial Stewardship.

PMID- 29444248
TI  - Comparative studies on the activities of collagenases from Grimontia hollisae and
      Clostridium hystoliticum in the hydrolysis of synthetic substrates.
AB  - The collagenase produced by a gram-negative bacterium Grimontia hollisae strain
      1706B (Ghcol) degrades collagen more efficiently than that produced by a gram
      positive bacterium Clostridium histolyticum (Chcol), which is currently the most
      widely used collagenase in industry [Teramura et al. (Cloning of a novel
      collagenase gene from the gram-negative bacterium Grimotia (Vibrio) hollisae
      1706B and its efficient expression in Brevibacillus choshinensis. J Bacteriol
      2011;193:3049-3056)]. Here, we compared the Ghcol and Chcol activities using two
      synthetic substrates. In the hydrolysis of (7-methoxycoumarin-4-yl)acetyl-L-Lys-L
      Pro-L-Leu-Gly-L-Leu-[N3-(2, 4-dinitrophenyl)-L-2, 3-diaminopropioyl]-L-Ala-L-Arg
      NH2, Ghcol exhibited 350-fold higher activity than Chcol in the absence of CaCl2
      and NaCl. The Ghcol activity markedly decreased with increasing concentrations of
      buffer, CaCl2 or NaCl, while the Chcol activity did not, suggesting that the
      Ghcol activity was sensitive to solvent components. In the hydrolysis of N-[3-(2
      furyl)acryloyl]-L-Leu-Gly-L-Pro-Ala, Ghcol exhibited 16-fold higher activity than
      Chcol in the absence of CaCl2 and NaCl, and both enzyme activities did not
      decrease with increasing concentrations of buffer, CaCl2 or NaCl. pH dependences
      of activity revealed that the ionizable group responsible for acidic pKe may be
      Glu for Ghcol and Chcol, while that for alkaline pKe may be His for Ghcol and Tyr
      for Chcol. These striking differences suggest that the catalytic mechanism of
      Ghcol might be considerably different from that of clostridial collagenases.

PMID- 29444249
TI  - Improvements scale-up and rapid response systems in the hospitals.

PMID- 29444250
TI  - Are elevated serum haemolysis markers a harbinger of adverse events in HeartMate
      II patients?
AB  - OBJECTIVES: Haemolysis during left ventricular assist device support is
      associated with thrombosis. In this retrospective study, we analysed whether low
      level haemolysis (LLH) as defined by simultaneously elevated lactate
      dehydrogenase (LDH) and free haemoglobin (fHb) levels had an impact on
      thromboembolic and bleeding events and on von Willebrand factor levels in
      HeartMate II patients. METHODS: After exclusion of patients with LDH >700 U/l and
      fHb >40 mg/dl at hospital discharge, 79 HeartMate II patients were included. LDH
      and fHb levels were measured at discharge and in 3 months interval. von
      Willebrand factor activity and antigen activity were measured 3 months
      postoperatively. Outcomes regarding ischaemic stroke (IS), pump thrombosis (PT)
      and gastrointestinal bleeding were recorded. Patients with LLH (400 < LDH <= 700
      U/l and 30 < fHb <= 40 mg/dl) at discharge (pre-Hemolyzers) were compared with
      the rest of the cohort (non-Hemolyzers). Competing risk analysis and Cox
      regression were applied for the comparison between groups. RESULTS: In all, 20%
      of the patients were identified as pre-Hemolyzers. Of these, 5 patients had PT
      and 3 patients had IS compared with 2 PT and 2 IS in the non-Hemolyzers group (P
      = 0.003 and P = 0.053, respectively). Fifty percent of the pre-Hemolyzers
      suffered gastrointestinal bleeding compared with 42% of the non-Hemolyzers (P =
      0.399). The cumulative risk of thromboembolic events (IS or PT) in the pre
      Hemolyzers group was significantly higher compared with the non-Hemolyzers group
      (hazard ratio 11.8, 95% confidence interval 3.7-37.7; P = 0.005). LLH did not
      have an impact on von Willebrand factor and the incidence of gastrointestinal
      bleeding. CONCLUSIONS: LLH as assessed by elevated fHb and LDH values at
      discharge during HeartMate II support is associated with thromboembolic events.

PMID- 29444251
TI  - Cultured equine satellite cells as a model system to assess leucine stimulated
      protein synthesis in horse muscle.
AB  - Leucine has been shown to stimulate the mammalian/mechanistic target of rapamycin
      (mTOR) signaling pathway which plays numerous key regulatory roles in cell
      growth, survival, and metabolism including protein synthesis in a number of
      species. However, previous work with equine satellite cells has suggested
      distinct species differences in regards to physiological effects and the
      magnitude of responses to growth factors and regulators. Because there is limited
      research available regarding the role of leucine in regulating equine skeletal
      muscle protein synthesis, the objective of this study was to evaluate the effect
      of leucine on the mTOR signaling pathway in cultured equine satellite. Protein
      synthesis was evaluated by measuring the incorporation of [3H] Phenylalanine
      (3HPhe) in equine satellite cell myotube cultures treated with a leucine
      titration ranging from 0 to 408 uM. Our results show a 1.8-fold increase (P <
      0.02) in protein synthesis at levels slightly greater than those found in the
      general circulation, 204 and 408 uM when compared to a no leucine control (0 uM).
      Puromycin incorporation, a nonradioactive surface sensing of translation (SUnSET)
      methodology, was also measured in cells treated with leucine (LEU; 408 uM), a no
      leucine control (CON), and a puromycin-negative vehicle (PURO-). These results
      demonstrated a 180% increase (P = 0.0056) in puromycin incorporation in LEU
      compared to CON cultures. To evaluate the mTOR signaling pathway, equine
      satellite cell myotube cultures were treated with leucine (LEU; 408 uM) or a no
      leucine control (CON) in the presence or absence of rapamycin (LR and CR,
      respectively), an inhibitor of mTOR. The mTOR inhibitor, rapamycin, suppressed
      phosphorylation of mTOR (P < 0.01) and rS6 (P < 0.01) with an increase in
      phosphorylation of rS6 in leucine-treated cultures observed when compared to
      control cultures (P < 0.05). Similarly, there was a 27% increase (P < 0.005) in
      the hyperphosphorylated gamma-form of 4E-BP1 compared to total 4E-BP1 in LEU
      compared to CON cultures with leucine-induced phosphorylation of 4E-BP1
      completely blocked by rapamycin with a smaller decrease observed in CR compared
      to CON cultures. The major finding of this study was that leucine activated the
      mTOR translation initiation pathway and increased transcription of global
      proteins in cultured equine satellite cells. Use of the cell culture system with
      primary equine muscle cell lines provides the opportunity to distinguish the
      impact of leucine on muscle and protein synthesis, independent of systemic
      interactions.

PMID- 29444253
TI  - HIV-1 genotypic resistance testing using the Vela automated next-generation
      sequencing platform.
AB  - Objectives: To evaluate the diagnostic performance of the Vela next-generation
      sequencing (NGS) system in conjunction with the Sentosa SQ HIV Genotyping Assay
      for genotyping HIV-1. Methods: Plasma RNA was extracted and templates prepared
      with the Sentosa SX instrument before sequencing the HIV-1 polymerase on the
      Sentosa SQ301 Sequencer (PGM IonTorrent). The Vela NGS System was compared with
      direct sequencing and the 454 GS-FLX (Roche) and MiSeq (Illumina) systems for
      genotypic resistance testing on clinical samples. Results: The Vela NGS system
      detected majority resistance mutations in subtype B and CRF02-AG samples at 500
      copies/mL and minority variants with a sensitivity of 5% at 100 000 copies/mL.
      The Vela NGS system and direct sequencing identified resistance mutations with
      97% concordance in 46 clinical samples. Vela identified 1/20 of the 1%-5%
      mutations identified by 454, 5/12 of the 5%-20% mutations and 60/61 of the >20%
      mutations. Vela identified 3/14 of the 1%-5% mutations identified by MiSeq, 0/2
      of the 5%-20% mutations and 47/47 of the >20% mutations. The resistance mutation
      quantifications by Vela and 454 were concordant (bias: 2.31%), as were those by
      Vela and MiSeq (bias: 1.06%). Conclusions: The Vela NGS system provides automated
      nucleic acid extraction, PCR reagent distribution, library preparation and
      bioinformatics analysis. The analytical performance was very good when compared
      with direct sequencing, but was less sensitive than two other NGS platforms for
      detecting minority variants.

PMID- 29444252
TI  - Human Striatal Response to Reward Anticipation Linked to Hippocampal Glutamate
      Levels.
AB  - Background: Dysfunctional reward processing is associated with a number of
      psychiatric disorders, such as addiction and schizophrenia. It is thought that
      reward is regulated mainly by dopamine transmission in the ventral striatum.
      Contemporary animal models suggest that striatal dopamine concentrations and
      associated behaviors are related to glutamatergic functioning in the ventral
      hippocampus. However, in humans the association between reward-related ventral
      striatal response and hippocampal glutamate levels is unclear. Methods: Nineteen
      healthy participants were studied using proton magnetic resonance spectroscopy to
      measure hippocampal glutamate levels, and functional magnetic resonance imaging
      to assess striatal activation and functional connectivity during performance of a
      monetary incentive delay task. Results: We found that ventral striatal activation
      related to reward processing was correlated with hippocampal glutamate levels. In
      addition, context-dependent functional coupling was demonstrated between the
      ventral striatum and both the lingual gyrus and hippocampus during reward
      anticipation. Elevated hippocampal glutamate levels were inversely related to
      context-dependent functional connectivity between the ventral striatum and the
      anterior hippocampus while anticipating reward. Conclusions: These findings
      indicate that human striatal responses to reward are influenced by hippocampal
      glutamate levels. This may be relevant for psychiatric disorders associated with
      abnormal reward processing such as addiction and schizophrenia.

PMID- 29444254
TI  - High-resolution esophageal manometry in a Mexican population: diagnostic outcome.
AB  - High-resolution esophageal manometry (HREM) has become the method of choice for
      evaluation of esophageal motility disorders. There is a paucity of data with this
      technique from Hispanic countries. This study aims to characterize the diagnostic
      outcome of HREM in a large cohort of consecutive patients in Mexico.This study
      was conducted in Monterrey, Mexico from March 1, 2013 to March 31, 2015. Our
      diverse study population included patients from a major academic institution and
      the community. HREM was done applying the Chicago Classification 3. Diagnostic
      outcome was grouped as weak peristaltic disorders, gastroesophageal junction
      disorders, and hypertensive/uncoordinated peristalsis.We studied 670 consecutive
      patients, 57% were women, mean age was 43.8 years. The majority (465 [69%]) were
      referred for preoperative evaluation of gastroesophageal reflux disease (GERD),
      365 (78%) of whom had a normal study. Overall, 193 (29%) patients had abnormal
      motility, the most common disorder being weak peristalsis (104 [54%]). In
      patients with dysphagia, the most frequent finding was achalasia (23/46 [50%]).To
      our knowledge, this is the first study to characterize the diagnostic outcome of
      HREM in a large cohort of Hispanic patients in Latin America. At our open access
      center, 69% of patients were referred for preoperative evaluation of GERD,
      reflecting the popularity of antireflux surgery. This study confirms the high
      prevalence of weak peristalsis and highlights the importance of addressing its
      pathophysiology and management. The finding of achalasia in 50% of our patients
      with dysphagia is consistent with recent reports regarding the rising incidence
      of this disorder and underscores the need of prompt motility testing in this
      population.

PMID- 29444256
TI  - Dose effect of patient-care team communication via secure portal messaging on
      glucose and blood pressure control.
AB  - Objectives: Organizational strategies for implementing eHealth tools influence
      patient and provider use of portal technology. This study examines whether the
      intensity of bidirectional secure portal messaging is associated with improved
      clinical outcomes. Material and Methods: This is a retrospective cohort analysis
      of 101 019 patients with diabetes or hypertension (11 138 active portal users)
      who received primary care within the Ochsner Health System between 2012 and 2014.
      Propensity score-adjusted multivariable fixed effects regression panel analysis
      was used to examine associations between intensity of "medical advice" portal
      messaging and glucose/blood pressure control. Results: Most portal users rarely
      used medical advice messaging. A higher proportion of patients who were age 50
      years and older, female, white non-Hispanic, and with co-morbid diabetes and
      hypertension had higher frequency and intensity of medical advice messaging.
      Study findings revealed a dose-response effect of the intensity of messaging on
      glucose control, whereby, compared to nonportal users, each level of messaging
      among portal users was associated with greater decreases in HbA1c (beta estimate
      [95% CI]: none -0.28 (-0.34 to -0.22); low -0.28 (-0.32 to -0.24); medium -0.41 (
      0.52 to -0.31); high -0.43 (-0.60 to -0.27), all P <= .001). There was no
      observed effect on blood pressure. Conclusions: The digital divide exists not
      only between portal users and nonusers but also among portal users. Research
      exploring the relationship between intensity of bidirectional secure messaging
      and health outcomes for a broader scope of chronic conditions is needed. Future
      implementation research must also elucidate best practices that enhance not only
      the use of portals by patients and providers, but how they use portals.

PMID- 29444255
TI  - Identification of the DNA methyltransferases establishing the methylome of the
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - DNA methylation in bacteria is important for defense against foreign DNA, but is
      also involved in DNA repair, replication, chromosome partitioning, and regulatory
      processes. Thus, characterization of the underlying DNA methyltransferases in
      genetically tractable bacteria is of paramount importance. Here, we characterized
      the methylome and orphan methyltransferases in the model cyanobacterium
      Synechocystis sp. PCC 6803. Single molecule real-time (SMRT) sequencing revealed
      four DNA methylation recognition sequences in addition to the previously known
      motif m5CGATCG, which is recognized by M.Ssp6803I. For three of the new
      recognition sequences, we identified the responsible methyltransferases.
      M.Ssp6803II, encoded by the sll0729 gene, modifies GGm4CC, M.Ssp6803III, encoded
      by slr1803, represents the cyanobacterial dam-like methyltransferase modifying
      Gm6ATC, and M.Ssp6803V, encoded by slr6095 on plasmid pSYSX, transfers methyl
      groups to the bipartite motif GGm6AN7TTGG/CCAm6AN7TCC. The remaining methylation
      recognition sequence GAm6AGGC is probably recognized by methyltransferase
      M.Ssp6803IV encoded by slr6050. M.Ssp6803III and M.Ssp6803IV were essential for
      the viability of Synechocystis, while the strains lacking M.Ssp6803I and
      M.Ssp6803V showed growth similar to the wild type. In contrast, growth was
      strongly diminished of the Deltasll0729 mutant lacking M.Ssp6803II. These data
      provide the basis for systematic studies on the molecular mechanisms impacted by
      these methyltransferases.

PMID- 29444257
TI  - Comparison of Strategies and Incidence Thresholds for Vi Conjugate Vaccines
      Against Typhoid Fever: A Cost-effectiveness Modeling Study.
AB  - Background: Typhoid fever remains a major public health problem globally. While
      new Vi conjugate vaccines hold promise for averting disease, the optimal
      programmatic delivery remains unclear. We aimed to identify the strategies and
      associated epidemiologic conditions under which Vi conjugate vaccines would be
      cost-effective. Methods: We developed a dynamic, age-structured transmission and
      cost-effectiveness model that simulated multiple vaccination strategies with a
      typhoid Vi conjugate vaccine from a societal perspective. We simulated 10-year
      vaccination programs with (1) routine immunization of infants (aged <1 year)
      through the Expanded Program on Immunization (EPI) and (2) routine immunization
      of infants through the EPI plus a 1-time catch-up campaign in school-aged
      children (aged 5-14 years). In the base case analysis, we assumed a 0.5% case
      fatality rate for all cases of clinically symptomatic typhoid fever and defined
      strategies as highly cost-effective by using the definition of a low-income
      country (defined as a country with a gross domestic product of $1045 per capita).
      We defined incidence as the true number of clinically symptomatic people in the
      population per year. Results: Vi conjugate typhoid vaccines were highly cost
      effective when administered by routine immunization activities through the EPI in
      settings with an annual incidence of >50 cases/100000 (95% uncertainty interval,
      40-75 cases) and when administered through the EPI plus a catch-up campaign in
      settings with an annual incidence of >130 cases/100000 (95% uncertainty interval,
      50-395 cases). The incidence threshold was sensitive to the typhoid-related case
      fatality rate, carrier contribution to transmission, vaccine characteristics, and
      country-specific economic threshold for cost-effectiveness. Conclusions: Typhoid
      Vi conjugate vaccines would be highly cost-effective in low-income countries in
      settings of moderate typhoid incidence (50 cases/100000 annually). These results
      were sensitive to case-fatality rates, underscoring the need to consider factors
      contributing to typhoid mortality (eg, healthcare access and antimicrobial
      resistance) in the global vaccination strategy.

PMID- 29444259
TI  - Atrial fibrosis associated with left ventricular apical hypoplasia.

PMID- 29444260
TI  - Comparative Proteomic Analysis of Plant Acclimation to Six Different Long-Term
      Environmental Changes.

PMID- 29444258
TI  - Modeling the Influence of Seasonal Differences in the HPA Axis on Synchronization
      of the Circadian Clock and Cell Cycle.
AB  - Synchronization of biological functions to environmental signals enables
      organisms to anticipate and appropriately respond to daily external fluctuations
      and is critical to the maintenance of homeostasis. Misalignment of circadian
      rhythms with environmental cues is associated with adverse health outcomes.
      Cortisol, the downstream effector of hypothalamic-pituitary-adrenal (HPA)
      activity, facilitates synchronization of peripheral biological processes to the
      environment. Cortisol levels exhibit substantial seasonal rhythmicity, with peak
      levels occurring during the short-photoperiod winter months and reduced levels
      occurring in the long-photoperiod summer season. Seasonal changes in cortisol
      secretion could therefore alter its entraining capabilities, resulting in a
      season-dependent modification in the alignment of biological activities with the
      environment. We develop a mathematical model to investigate the influence of
      photoperiod-induced seasonal differences in the circadian rhythmicity of the HPA
      axis on the synchronization of the peripheral circadian clock and cell cycle in a
      heterogeneous cell population. Model simulations predict that the high-amplitude
      cortisol rhythms in winter result in the greatest entrainment of peripheral
      oscillators. Furthermore, simulations predict a circadian gating of the cell
      cycle with respect to the expression of peripheral clock genes. Seasonal
      differences in cortisol rhythmicity are also predicted to influence mitotic
      synchrony, with a high-amplitude winter rhythm resulting in the greatest
      synchrony and a shift in timing of the cell cycle phases, relative to summer. Our
      results highlight the primary interactions among the HPA axis, the peripheral
      circadian clock, and the cell cycle and thereby provide an improved understanding
      of the implications of circadian misalignment on the synchronization of
      peripheral regulatory processes.

PMID- 29444261
TI  - Selective Androgen Receptor Modulator S42 Suppresses Prostate Cancer Cell
      Proliferation.
AB  - We previously identified the selective androgen receptor (AR) modulator S42,
      which does not stimulate prostate growth but has a beneficial effect on lipid
      metabolism. In the prostate cancer (PC) cell line LNCaP, S42 did not induce AR
      transactivation but antagonized 5alpha-dihydrotestosterone (DHT)-induced AR
      activation. Next, we investigated whether S42 suppresses the growth of PC cell
      lines. Basal growth of LNCaP cells was significantly suppressed by treatment with
      S42 compared with vehicle, as determined by cell counting and 5-bromo-2'
      deoxyuridine assays. The suppressive effect of S42 on cell growth was evident in
      the AR-positive PC cells LNCaP and 22Rv1 and was slightly observed even in the AR
      negative PC-3 cells. However, S42 did not induce apoptosis as determined by the
      terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay. S42
      had an even greater suppressive effect on DHT-dependent LNCaP cell proliferation
      than on basal proliferation (P < 0.05). DHT treatment increased the expression of
      phosphorylated extracellular signal-regulated kinase (ERK)-mitogen-activated
      protein kinase (MAPK), a major signaling molecule for PC proliferation, and this
      was significantly inhibited by S42. DHT also significantly upregulated AR,
      insulinlike growth factor-1 receptor (IGF-1R), and insulin receptor (IR)-beta
      protein levels, which were similarly reduced by S42 treatment. Importantly, S42
      administration to mice attenuated the growth of LNCaP tumors and reduced tumor
      expression of the prostate-specific antigen, P504S, Ki67, and phosphorylated ERK
      MAPK. These data suggest that S42 attenuates LNCaP tumor growth not by inducing
      apoptosis but by inhibiting the expression of proliferation-related receptors,
      including IGF-1R, IR, and AR, and by suppressing ERK-MAPK activation. S42 may
      thus be a feasible candidate for PC treatment.

PMID- 29444262
TI  - Plant Cuttings: news in Botany.

PMID- 29444263
TI  - Bilateral Venous Sinus Stenosis: Idiopathic Intracranial Hypertension and
      Endovascular Venous Sinus Stenting: 2-Dimensional Operative Video.

PMID- 29444264
TI  - Underestimation of spirometry if recommended testing guidance is not followed.
AB  - Background: Lung function measured at work is used to make important employment
      decisions. Improving its quality will reduce misclassification and allow more
      accurate longitudinal interpretation over time. Aims: To assess the amount by
      which lung function (forced expiratory volume in 1 second [FEV1] and forced vital
      capacity [FVC]) values will be underestimated if recommended spirometry testing
      guidance is not followed. Methods: Lung function was measured in a population of
      workers. Knowledge of the final reproducible FEV1 and FVC for each worker allowed
      estimation of the underestimates that would have occurred if less forced
      manoeuvres than recommended had been performed. Results: A total of 667 workers
      (661 males, mean age 43 years, range 18-66) participated. Among them, 560 (84%)
      achieved reproducible results for both FEV1 and FVC; 470 (84%) of these did so
      after three technically acceptable forced expiratory manoeuvres, a cumulative
      total of 533 after four, 548 after five, 557 after six, 559 after seven and 560
      after eight blows. If only one (or first two) technically acceptable blow(s) had
      been performed, mean underestimates were calculated for FEV1 of 115.1 ml (35.4
      ml) and for FVC of 143.4 ml (42.3 ml). Conclusions: In this study, reproducible
      spirometry was achievable in most workers. Not adhering to standards
      underestimates lung function by clinically significant amounts.

PMID- 29444265
TI  - Ice algal bloom development on the surface of the Greenland Ice Sheet.
AB  - It is fundamental to understand the development of Zygnematophycean
      (Streptophyte) micro-algal blooms within Greenland Ice Sheet (GrIS) supraglacial
      environments, given their potential to significantly impact both physical (melt)
      and chemical (carbon and nutrient cycling) surface characteristics. Here, we
      report on a space-for-time assessment of a GrIS ice algal bloom, achieved by
      sampling an ~85 km transect spanning the south-western GrIS bare ice zone during
      the 2016 ablation season. Cell abundances ranged from 0 to 1.6 * 104 cells ml-1,
      with algal biomass demonstrated to increase in surface ice with time since snow
      line retreat (R2 = 0.73, P < 0.05). A suite of light harvesting and photo
      protective pigments were quantified across transects (chlorophylls, carotenoids
      and phenols) and shown to increase in concert with algal biomass. Ice algal
      communities drove net autotrophy of surface ice, with maximal rates of net
      production averaging 0.52 +/- 0.04 mg C l-1 d-1, and a total accumulation of
      1.306 Gg C (15.82 +/- 8.14 kg C km-2) predicted for the 2016 ablation season
      across an 8.24 * 104 km2 region of the GrIS. By advancing our understanding of
      ice algal bloom development, this study marks an important step toward projecting
      bloom occurrence and impacts into the future.

PMID- 29444267
TI  - Safety of Laser Interstitial Thermal Therapy in Patients With Pacemakers.
AB  - BACKGROUND AND IMPORTANCE: Laser interstitial thermal therapy (LiTT) has
      increasingly been used as a treatment option for medically refractory epilepsy,
      tumors, and radiation necrosis. The use of LiTT requires intraoperative magnetic
      resonance (MR) thermography. This can become an issue in patients with other
      implanted therapeutic devices such as pacemakers and vagal nerve stimulators due
      to concerns regarding increases in the specific absorption rate (SAR). This is a
      technical case report demonstrating a successfully and safely performed LiTT in a
      1.5-T magnetic resonance imaging (MRI) in a patient with a pacemaker for mesial
      temporal sclerosis. CLINICAL PRESENTATION: An 83-yr-old gentleman who had an
      implanted cardiac pacemaker presented with medically intractable epilepsy and was
      confirmed to have mesial temporal sclerosis on imaging. Video
      electroencephalography demonstrated concordant ipsilateral seizures and
      semiology. He underwent LiTT for ablation of the mesial temporal lobe. This was
      performed with the below described protocol with a cardiology nurse monitoring
      the patient's cardiac condition and a physicist monitoring SAR, and MR imaging
      quality without any adverse events. CONCLUSION: This study reports on a protocol
      of cardiac and MR SAR to safely perform MR-guided LiTT in the setting of
      traditional pacemakers in patients who are not pacemaker dependent.

PMID- 29444268
TI  - Advancing Tobacco Product Warning Labels Research Methods and Theory: A Summary
      of a Grantee Meeting Held by the US National Cancer Institute.
AB  - Background: The World Health Organization's Framework Convention on Tobacco
      Control recommends prominent pictorial health warnings on tobacco products. To
      advance research methods, theory and understanding of how tobacco product warning
      labels (TPWLs) work, the US National Cancer Institute convened a grantee meeting.
      Our article describes the key insights that emerged from the meeting, situated
      within the context of the scientific literature. Results & Recommendations:
      First, presentations confirmed that large, pictorial TPWLs motivate people to try
      to quit and encourage smoking cessation. Second, pictorial TPWLs increase
      attention, knowledge, negative affect, and thinking about the warning. Third,
      TPWL studies have primarily used brief-exposure laboratory studies and
      observational studies of sustained exposure through national policy
      implementation, with a few randomized trials involving several weeks of exposure
      with generally consistent results found across study designs. Fourth, novel
      assessment methods include brain imaging, eye tracking and "best-worst" discrete
      choice experiments. To make TPWL even more effective, research is needed to
      confirm the mechanisms of their influence, their impact across vulnerable
      populations, and their effect on social media posts about tobacco products.
      Research is also needed on the effect of trial design choices, the predictive
      validity of new measurement approaches, and warning labels for non-cigarette
      tobacco products. Implications: To improve scientific understanding of TPWL
      effects, this grantee meeting summary describes emerging research methods, theory
      and study results. Directions for future research include examination of the
      mechanisms of how warning labels work across diverse tobacco products and across
      different populations and contexts.

PMID- 29444266
TI  - Fundamentals of glycogen metabolism for coaches and athletes.
AB  - The ability of athletes to train day after day depends in large part on adequate
      restoration of muscle glycogen stores, a process that requires the consumption of
      sufficient dietary carbohydrates and ample time. Providing effective guidance to
      athletes and others wishing to enhance training adaptations and improve
      performance requires an understanding of the normal variations in muscle glycogen
      content in response to training and diet; the time required for adequate
      restoration of glycogen stores; the influence of the amount, type, and timing of
      carbohydrate intake on glycogen resynthesis; and the impact of other nutrients on
      glycogenesis. This review highlights the practical implications of the latest
      research related to glycogen metabolism in physically active individuals to help
      sports dietitians, coaches, personal trainers, and other sports health
      professionals gain a fundamental understanding of glycogen metabolism, as well as
      related practical applications for enhancing training adaptations and preparing
      for competition.

PMID- 29444269
TI  - Association of angiotensin II type 1 receptor antibodies with graft histology,
      function and survival in paediatric renal transplant recipients.
AB  - Background: We analysed in a carefully phenotyped cohort of paediatric patients
      the association of serum angiotensin II type 1 receptor antibodies (AT1R-Ab) with
      specific histological lesions and with graft function and survival in conjunction
      with overall and complement-binding donor-specific human leucocyte antigen donor
      specific antibodies (HLA-DSA). Methods: Sera of 62 patients at the time of renal
      graft biopsy for clinical indication >1 year post-transplant were assessed for
      AT1R-Ab by enzyme-linked immunosorbent assay (ELISA) and for DSA and C1q-fixing
      DSA by single-antigen bead technology. Results: Serum AT1R-Ab concentration was
      significantly higher in antibody-mediated rejection (ABMR) than in T-cell
      mediated rejection or control. By receiver operating characteristic (ROC) curve
      analysis, the optimal AT1R-Ab cut-off value discriminating between patients with
      features of ABMR and those without was 9.5 U/mL. A total of 6 of 28 patients
      (21.4%) with ABMR were only positive for AT1R-Ab. Patients with AT1R-Ab and HLA
      DSA double positivity had a significantly higher vascular micro-inflammation
      score than DSA-negative patients. The 5-year graft survival was only 59% in the
      AT1R-Ab-positive group compared with 87% in the AT1R-Ab-negative group. Patients
      with AT1R-Ab and HLA-DSA double positivity tended to have a more rapid decline of
      estimated glomerular filtration rate (eGFR) than patients who were only positive
      for AT1R-Ab or HLA-DSA. In a multivariate Cox regression model of non-invasive
      factors, C1q-positive HLA-DSA, eGFR and AT1R-Ab positivity were significantly
      associated with accelerated graft function decline. Conclusions: Serum AT1R-Ab
      positivity in the context of an indication biopsy >1 year post-transplant is
      associated with the histopathology of ABMR and is an independent non-invasive
      risk factor for adverse graft outcome.

PMID- 29444270
TI  - Efficacy and Outcomes of Posterior Inferior Cerebellar Artery (PICA) Bypass for
      Proximal PICA and Vertebral Artery-PICA Aneurysms: A Case Series.
AB  - BACKGROUND: Nonsaccular vertebral artery (VA) and posterior inferior cerebellar
      artery (PICA) aneurysms have high morbidity and mortality rates and are difficult
      to treat using standard microsurgical or endovascular techniques. Definitive
      revascularization can require clip trapping and/or vessel sacrifice, with PICA
      bypass. The published surgical experience with these approaches is limited. We
      herein review our recent surgical experience with PICA revascularization for
      complex PICA and VA/PICA aneurysms. OBJECTIVE: To determine the efficacy and
      outcomes of PICA bypass for revascularization of nonsaccular PICA and VA/PICA
      aneurysms. METHODS: Retrospective analysis of an institutional review board
      approved, prospective database was performed to identify patients with PICA and
      VA/PICA aneurysms treated with PICA bypass at a single institution. Demographic
      information, aneurysm characteristics, temporary clip time, and neurological
      outcomes were recorded. RESULTS: Ten cases of PICA revascularization were
      performed for both ruptured (n = 8) and unruptured (n = 2) nonsaccular proximal
      PICA or VA/PICA aneurysms. Seven cases were performed without vessel grafts; 3
      cases required harvest of the descending branch of the lateral femoral circumflex
      artery. Mean temporary clip time was 38 min (range 27-50 min). Good outcomes
      (Glasgow Outcomes Scale score of 5) were achieved in 70% (n = 7) of patients at
      time of discharge; the remaining patients had a Glasgow Outcomes Scale of 3. Two
      bypass-related complications occurred in this series; a hematoma at the graft
      harvest site requiring evacuation, and severe bypass graft spasm requiring
      multiple endovascular treatments. CONCLUSION: PICA bypass can be a safe,
      effective, and highly customizable tool for the revascularization of patients
      with nonsaccular proximal PICA and VA/PICA aneurysms.

PMID- 29444272
TI  - Right Far-Lateral Approach for Resection of Foramen Magnum Meningioma: 3
      Dimensional Operative Video.

PMID- 29444271
TI  - Molecular characterization of second tomato alpha1,3/4-fucosidase (alpha-Fuc'ase
      Sl-2), a member of glycosyl hydrolase family 29 active toward the core alpha1,3
      fucosyl residue in plant N-glycans.
AB  - In a previous study, we molecular-characterized a tomato (Solanum lycopersicum)
      alpha1, 3/4-fucosidase (alpha-Fuc'ase Sl-1) encoded in a tomato gene
      (Solyc03g006980), indicating that alpha-Fuc'ase Sl-1 is involved in the turnover
      of Lea epitope-containing N-glycans. In this study, we have characterized another
      tomato gene (Solyc11g069010) encoding alpha1, 3/4-fucosidase (alpha-Fuc'ase Sl
      2), which is also active toward the complex type N-glycans containing Lea
      epitope(s). The baculovirus-insect cell expression system was used to express
      that alpha-Fuc'ase Sl-2 with anti-FLAG tag, and the expression product (rFuc'ase
      Sl-2), was found as a 65 kDa protein using SDS-PAGE and has an optimum pH of
      around 5.0. Similarly to rFuc'ase Sl-1, rFuc'ase Sl-2 hydrolyzed the non-reducing
      terminal alpha1, 3-fucose residue on LNFP III and alpha1, 4-fucose residues of
      Lea epitopes on plant complex type N-glycans, but not the core alpha1, 3-fucose
      residue on Manbeta1-4GlcNAcbeta1-4(Fucalpha1-3)GlcNAc or Fucalpha1-3GlcNAc.
      However, we found that both alpha-Fuc'ases Sl-1 and Sl-2 were specifically active
      toward alpha1, 3-fucose residue on GlcNAcbeta1-4(Fucalpha1-3)GlcNAc, indicating
      that the non-substituted beta-GlcNAc linked to the proximal GlcNAc residue of the
      core tri-saccharide moiety of plant specific N-glycans must be a pre-requisite
      for alpha-Fuc'ase activity. A 3 D modelled structure of the catalytic sites of
      alpha-Fuc'ase Sl-2 suggested that Asp192 and Glu236 may be important for binding
      to the alpha1, 3/4 fucose residue.

PMID- 29444273
TI  - Prevalence and determinants in cytology testing for cervical cancer screening in
      Spain (2006-14).
AB  - Background: Cervical cancer has decreased in developed countries thanks to
      cytology screening programmes. The aims of this study were To analyse the
      frequency and evolution of performing cytology tests and to determine the
      variables that influence their use. Methods: Cross-sectional study of non
      institutionalized women who participated in the national health survey (2006,
      2011/12) and the European Health Survey in Spain (2009, 2014). Study variables:
      cytology-testing, time since last cytology-test, reason for performing the test,
      age, nationality, marital status, social status, education level and place of
      residence. Results: The study evaluated 53 628 women in Spain over 15 years old,
      with a mean age of 52.68 (SD +/- 19.12). About 94.1% were Spanish, 49.2% were
      married and 77.2% lived with a partner. In 2014, 72% had a cytology test, a
      number that increased significantly. Women aged 25-65 were 5.13 times more likely
      to undergo a cytology test than those aged 15-24 years old (odds ratio (OR):
      5.13; P < 0.001); women with university educations were 9.23 times more likely to
      undergo a cytology test than those without university educations (P > 0.001);
      those of social classes I and II (high) were 1.2 more likely to undergo a
      cytology test than those of low social class (P = 0.026); and Spanish women were
      1.74 times more likely to undergo a cytology test than foreigners living in Spain
      (P < 0.001). Conclusion: Frequency of cytology testing has increased in the last
      few years. Screening for cervical cancer is associated with higher social status,
      education level, age, and not being foreign.

PMID- 29444274
TI  - Shift work, parental cardiovascular disease and myocardial infarction in males.
AB  - Background: Shift work has been associated with an increased risk of
      cardiovascular disease (CVD). However, there is a need for more studies to
      determine whether there is an interaction between shift work and other risk
      factors of CVD, thereby increasing the risk of CVD in shift workers. Aims: To
      discern whether shift work and parental mortality from myocardial infarction (MI)
      or sudden cardiac death (SCD) interact to increase the risk of MI in men.
      Methods: A case-control dataset was used to assess interaction between shift work
      and parental history of CVD, using death from MI or SCD, or death before age 65,
      on an additive scale. Results were reported as relative excess risk due to
      interaction, attributable proportion due to interaction (AP) and synergy index
      (SI). Results: There was an interaction between shift work and paternal mortality
      from MI or SCD, when both factors were present [SI = 2.39; 95% confidence
      interval (CI) 1.02-5.6 and AP = 0.4; 95% CI 0.08-0.73]. Conclusions: Paternal
      mortality from MI or SCD interacts with shift work to increase the risk of MI in
      men.

PMID- 29444275
TI  - E-cigarette Advertising Exposure, Explicit and Implicit Harm Perceptions, and E
      Cigarette use Susceptibility Among Non-Smoking Young Adults.
AB  - Introduction: This study tested whether exposure to e-cigarette advertising
      increases e-cigarette use susceptibility among non-smoking young adults by
      promoting explicit and implicit attitudes towards e-cigarettes as a safer and
      healthier alternative to combustible cigarettes. Methods: Young adult current non
      smokers who had never used an e-cigarette (N = 393; Mean age = 22.1, Standard
      Deviation = 3.9; 66% Women) were randomly assigned to one of the 3 conditions
      that involved viewing real-world, print e-cigarette ads. Two of the 3 conditions
      were experimental conditions where ads with different predominant themes [harm
      reduction ("Health") vs. social enhancement ("Social") focused] were interspersed
      among ads of everyday objects. The third condition was the control condition
      involving ads of everyday objects only. Participants provided data on explicit
      (i.e., self-reported harm perceptions) and implicit (i.e., Implicit Association
      Test) attitudes towards e-cigarette use and e-cigarette use intentions.
      Hypotheses were tested using structural equation modeling. Results: Relative to
      Control participants, participants in Health and Social conditions were more
      likely to show higher implicit attitudes towards e-cigarettes as a safer
      alternative to cigarettes. Only the Social condition, relative to Control, had a
      significant effect on lower explicit harm perceptions of e-cigarette versus
      cigarette use. The Social condition had a significant indirect effect on e
      cigarette use susceptibility, mediated by explicit harm perceptions. Conclusions:
      Social enhancement-themed ads may communicate the reduced-harm messages more
      strongly among young adults so as to affect both explicit and implicit attitudes
      and, through these, e-cigarette use susceptibility. Regulatory bodies may need to
      scrutinize reduced-harm claims communicated through social enhancement-themed
      ads.

PMID- 29444276
TI  - Extracorporeal resuscitation as a further modifier of clinical outcome in
      patients with left ventricular assist device implantation and Interagency
      Registry for Mechanically Assisted Circulatory Support level 1.
AB  - In cardiogenic shock patients with Interagency Registry for Mechanical
      Circulatory Support (INTERMACS) level 1, the need for temporary circulatory
      support is a predictor and modifier of patient outcome. Because this group
      includes patients with and without cardiopulmonary resuscitation (CPR) and is
      thus very heterogeneous, we investigated whether a further subclassification is
      useful. We compared 30-day and 1-year mortality of patients who underwent left
      ventricular assist device implantation after extracorporeal CPR with the aid of
      an extracorporeal life support system (CPR+ group; n = 40) with cardiogenic shock
      patients in which the extracorporeal life support system was implanted under non
      CPR conditions (CPR- group, n = 68). In the CPR+ and CPR- groups, 30-day
      mortality was 27.5% (n = 11) and 8.8% (n = 6), respectively (P = 0.014). The
      values for 1-year mortality were 57.5% (n = 23) and 36.8% (n = 25), respectively
      (P = 0.023). The age- and gender-adjusted hazard ratios of 30-day and 1-year
      mortality for the CPR+ group and the CPR- group were 3.88 (95% confidence
      interval 1.29-11.7; P = 0.016) and 1.79 (95% confidence interval 1.01-3.17; P =
      0.045), respectively. In conclusion, our data show that left ventricular assist
      device implantation with extracorporeal life support following CPR is associated
      with high 30-day and 1-year mortality. Further multicentre studies are needed to
      confirm these results and potentially add CPR as a new modifier to the INTERMACS
      profile.

PMID- 29444277
TI  - Pathophysiology and Management of Abdominal Myofascial Pain Syndrome (AMPS): A
      Three-Year Prospective Audit of a Management Pathway in 120 Patients.
AB  - Background: Chronic abdominal wall pain arising from the myofascial structures is
      termed abdominal myofascial pain syndrome and is an important cause of refractory
      abdominal pain that utilizes significant health care costs. The current
      literature is vague on its management. Design: The author presents a prospective
      audit of a structured management pathway and discusses the pathophysiology of
      abdominal myofascial pain syndrome. The objective was to identify an effective
      and durable treatment for the individual patient and evaluate patient
      satisfaction with the management pathway. Methods: Over a three-year period, 120
      patients diagnosed with abdominal myofascial pain syndrome were included in a
      structured management pathway and were prospectively audited at a tertiary care
      university hospital. Results: Patient satisfaction with the pathway was high.
      Trigger point injection with local anesthetic was useful in diagnosis but
      ineffective in providing durable relief. Trigger point injection with steroids
      and pulsed radiofrequency treatment of trigger point(s) were effective
      therapeutic interventions, providing durable relief lasting six months in 32% and
      60%, respectively. There was improvement reported in pain intensity scores,
      quality of life, anxiety, and depression scores following the interventional
      management of abdominal myofascial pain syndrome. Conclusions: Abdominal
      myofascial pain syndrome is often unrecognized, especially in patients with a
      history of visceral inflammation. The suggested pathway may be an option in its
      management. Trigger point injection with steroids may have a role in the
      differential diagnosis of chronic abdominal pain.

PMID- 29444278
TI  - Effectiveness of modified oral steroid administration for preventing esophageal
      stricture after entire circumferential endoscopic submucosal dissection.
AB  - Esophageal stricture occurs at a high rate after endoscopic submucosal
      dissection, especially after entire circumferential dissection, leading to poor
      quality of life. This retrospective cohort study evaluated the stricture rate in
      circumferential mucosal defect cases following modified steroid administration.
      We enrolled 22 consecutive patients who underwent entire circumferential
      endoscopic submucosal dissection for superficial esophageal cancer between April
      2010 and April 2015 at our hospital. Until January 2013, a systemic steroid
      prednisolone-was administered at 30 mg/day and tapered over 8 weeks in the
      original method group (original group). From February 2013, 30 mg of prednisolone
      was administered orally for 3 weeks and then the dose was reduced in 5 mg
      decrements every 3 weeks. This group was classified as the modified method group
      (modified group). We retrospectively compared the stricture rates between the two
      groups. The postoperative stricture rate was significantly lower in the modified
      group (36.4%; 4/11 patients) than in the original group (82%; 9/11 patients; P =
      0.04). The mean number of endoscopic balloon dilatation procedures was
      significantly lower in the modified group (6.2 +/- 11.3) than in the original
      group (19.4 +/- 15.3; P = 0.023). Pneumonia and oral herpes infection, which are
      adverse events potentially associated with steroid administration, were observed
      in the original group. Candida esophagitis, arthritis, and steroid-related
      myopathy were observed in the modified group. This modified systemic steroid
      administration was effective for patients with entire circumferential mucosal
      defect. The safety of this method was also demonstrated.

PMID- 29444279
TI  - Adult Brainstem Gliomas With H3K27M Mutation: Radiology, Pathology, and
      Prognosis.
AB  - Adult brainstem gliomas are difficult to classify based on radiologic and
      histologic features. A K27M mutation in histone 3 has been described to identify
      high-grade midline gliomas associated with a particularly unfavorable prognosis.
      While initially considered a pediatric entity, it is now known that H3K27M-mutant
      brainstem gliomas occur in all age groups, but they are less well understood in
      adults. We studied clinical, radiologic, and pathologic features of 25 brainstem
      gliomas diagnosed at our institution between 1994 and 2017 in subjects at least
      18 years old. Seven tumors (28%) were positive for the H3K27M mutation, and their
      median overall survival was significantly shorter than in the H3-wildtype group
      (p = 0.004). Although the mutation was invariably associated with a poor
      prognosis, our study also illustrates the radiologic and pathologic heterogeneity
      in this molecular tumor subtype. The results showed that H3K27M-mutant status and
      clinically aggressive course cannot be ruled out based on low-grade histology on
      the initial biopsy, exophytic growth, only focal or minimal enhancement or an
      extrapontine location, such as midbrain or medulla. These results favor an
      integrated approach employing a combination of clinical, radiologic, histologic
      features as well as H3K27M immunohistochemistry for the diagnostic
      subclassification of adult brainstem gliomas.

PMID- 29444280
TI  - Prevalence of dementia in mainland China, Hong Kong and Taiwan: an updated
      systematic review and meta-analysis.
AB  - Background: There are several existing systematic reviews of prevalence of
      dementia for mainland China, Hong Kong and Taiwan, but several studies have been
      newly reported. The aim of this study is to update prevalence data in this region
      and test for variation across geographical areas and time periods using the new
      dataset. Methods: Twenty prevalence studies identified from World Alzheimer
      Report 2015 (January 2011-March 2015) and an updated search (March 2015-February
      2017) were added to the original dataset (N = 76). Meta-regression was used to
      investigate geographical variation and time trends, taking methodological factors
      and characteristics of study population into account, and to estimate prevalence
      and number of people with dementia by geographical area. Results: Compared with
      northern China, the prevalence of dementia was lower in the central China [-1.0;
      95% confidence interval (CI):-2.2, 0.3], south China (-1.7; 95% CI: -3.1, -0.3),
      Hong Kong and Taiwan (-3.0; 95% CI: -5.0, -1.0) but appeared to be higher in
      western China (2.8; 95% CI: 0.1, 5.5) after adjusting for methodological
      variation. The increasing trend from pre-1990 to post-2010 periods was
      considerably attenuated when taking into account methodological factors and
      geographical areas. The updated estimated number of people with dementia in all
      these areas is 9.5 million (5.3%; 95% CI: 4.3, 6.3) in the population aged 60 or
      above. Conclusions: Geographical variation in dementia prevalence is confirmed in
      this update, whereas evidence on increasing trends is still insufficient.
      Differing societal development across areas provides an opportunity to
      investigate risk factors at the population level operating across diverse life
      course experiences. Such research could advance global primary prevention of
      dementia.

PMID- 29444282
TI  - Microsurgical Resection of Large Thoracic Intramedullary Hemangioblastoma With
      Long Segment Syrinx: 3-Dimensional Operative Video.

PMID- 29444281
TI  - Surgical management of esophageal sarcoma: a multicenter European experience.
AB  - Esophageal sarcomas are rare and evidence in literature is scarce making their
      management difficult. The objective is to report surgical and oncological
      outcomes of esophageal sarcoma in a large multicenter European cohort. This is a
      retrospective multicenter study including all patients who underwent en-bloc
      esophagectomy for esophageal sarcoma in seven European tertiary referral centers
      between 1987 and 2016. The main outcomes and measures are pathological results,
      early and long-term outcomes. Among 10,936 esophageal resections for cancer, 21
      (0.2%) patients with esophageal sarcoma were identified. The majority of tumors
      was located in the middle (n = 7) and distal (n = 9) third of the esophagus.
      Neoadjuvant chemoradiotherapy was performed in five patients. All the patients
      underwent en-bloc transthoracic esophagectomy (19 open, 2 minimally invasive).
      Postoperative mortality occurred in 1 patient (5%). One patient received adjuvant
      chemotherapy. Definitive pathological results were carcinosarcoma (n = 7),
      leiomyosarcoma (n = 5), and other types of sarcoma (n = 9). Microscopic R1
      resection was present in one patient (5%) and seven patients (33%) had positive
      lymph nodes. Median follow-up was 16 (3-79) months in 20 of 21 patients (95%).
      One-, 3-, and 5-year overall survival rates were 74%, 43%, and 35%, respectively.
      One-, 3- and 5-years disease-free survival rates were 58%, 40%, and 33%,
      respectively. Median overall survival was 6 months in N+ patients vs. 37 months
      for N0 patients (p = 0.06). At the end of the follow-up period, nine patients had
      died from cancer recurrences (43%), three patients died from other reasons (14%),
      one patient was still alive with recurrence (5%) and the seven remaining patients
      were free of disease (33%). Recurrence was local (n = 3), metastatic (n = 3), or
      both (n = 4). In conclusion, carcinosarcoma and leiomyosarcoma were the most
      common esophageal sarcoma histological subtypes. Lymph node involvement was seen
      in one third of cases. A transthoracic en-bloc esophagectomy with radical
      lymphadenectomy should be the best surgical option to achieve complete resection.
      Long-term survival remained poor with a high local and distant recurrence rate.

PMID- 29444283
TI  - Designing risk prediction models for ambulatory no-shows across different
      specialties and clinics.
AB  - Objective: As available data increases, so does the opportunity to develop risk
      scores on more refined patient populations. In this paper we assessed the ability
      to derive a risk score for a patient no-showing to a clinic visit. Methods: Using
      data from 2 264 235 outpatient appointments we assessed the performance of models
      built across 14 different specialties and 55 clinics. We used regularized
      logistic regression models to fit and assess models built on the health system,
      specialty, and clinic levels. We evaluated fits based on their discrimination and
      calibration. Results: Overall, the results suggest that a relatively robust risk
      score for patient no-shows could be derived with an average C-statistic of 0.83
      across clinic level models and strong calibration. Moreover, the clinic specific
      models, even with lower training set sizes, often performed better than the more
      general models. Examination of the individual models showed that risk factors had
      different degrees of predictability across the different specialties.
      Implementation of optimal modeling strategies would lead to capturing an
      additional 4819 no-shows per-year. Conclusion: Overall, this work highlights both
      the opportunity for and the importance of leveraging the available electronic
      health record data to develop more refined risk models.

PMID- 29444284
TI  - Gentamicin-intercalated smectite as a new therapeutic option for Helicobacter
      pylori eradication.
AB  - Objectives: Novel antibacterial strategies against Helicobacter pylori are needed
      because H. pylori strains are acquiring resistance to antibiotics. We evaluated
      the efficacy of gentamicin-intercalated smectite hybrid (S-GEN)-based treatment
      regimens in a murine model of H. pylori infection. Methods: Two groups of 10 rats
      were administered either smectite or S-GEN to measure coverage of the gastric
      mucosa. To evaluate anti-H. pylori efficacy, mice were divided into eight groups
      of 10 mice each given different treatments, and H. pylori eradication was
      assessed by a Campylobacter-like organism (CLO) test and H. pylori PCR of the
      gastric mucosa, and H. pylori antigen and H. pylori PCR analysis of mouse faeces.
      The levels of proinflammatory cytokines were examined. Results: S-GEN was
      retained in the gastric mucosal layer with a >60% distribution ratio for up to 1
      h, and the S-GEN-based triple regimen decreased bacterial burden in vivo compared
      with that of untreated mice or mice treated with other regimens. The cure rates
      in the CLO test and H. pylori PCR from gastric mucosa were 70%, 60%, 80%, 50%,
      60% and 60% in Groups III-VIII, respectively. Those for H. pylori PCR in the
      faeces of mice were 90% and 100% in Group III with standard therapy and Group V
      with triple therapy including S-GEN, respectively. S-GEN triple therapy also
      reduced the levels of proinflammatory cytokines. Conclusions: These results
      suggest that S-GEN is a promising and effective therapeutic agent for the
      treatment of H. pylori infection.

PMID- 29444285
TI  - The role of skeletal muscle in the pathophysiology and management of knee
      osteoarthritis.

PMID- 29444286
TI  - Techniques to Ensure Accurate Targeting for Delivery of Awake Laser Interstitial
      Thermotherapy.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) guided laser interstitial thermal
      therapy (LITT) is an emerging neurosurgical treatment modality that is typically
      performed under general anesthesia. We describe a novel workflow developed at the
      University of Florida to deliver LITT in conscious patients without the use of
      general anesthesia. OBJECTIVE: To describe a novel workflow for LITT
      implementation in the awake patient with equivalent treatment results when
      compared to procedures performed under general anesthesia. METHODS: For
      trajectories near a post of the Cosman-Roberts-Wells (CRW) frame (Integra
      LifeSciences, Plainsboro, New Jersey), we used preoperative MRI imaging to 3
      dimensional-print a patient-specific mask with a trajectory guide to indicate the
      planned entry point during headframe placement. Otherwise, routine headframe
      placement and stereotactic registration were performed. Stereotactic biopsy and
      placement of the cranial bolt were performed in a standard neurosurgical
      operating room. The patient was transferred to a diagnostic MRI suite and
      positioned in the MRI scanner using beanbags and a custom molded thermoplastic
      mask. LITT was delivered with the patient conscious in the MRI scanner according
      to the manufacturer's recommendations. We collected patient demographics,
      treatment time, length of stay, and calculated preoperative tumor volume and
      postoperative ablation volumes. RESULTS: Ten sequential patients were treated
      with LITT from January 2016 until March 2017. The average preoperative tumor
      volume was 6.9 cm3. The average tissue volume ablated was 18.3 cm3. The mean
      operative time was 31 min (standard deviation [SD] 10 min) and mean time with
      laser delivery in MRI was 79 min (SD 27 min). The mean length of stay was 1.4 d
      (SD 0.9). There were no major complications. CONCLUSION: Using trajectory
      preplanning, customized face masks, and noninvasive head immobilization, LITT can
      be delivered to patients safely and accurately without general anesthesia.

PMID- 29444287
TI  - Mosquitoes of Northwestern Uganda.
AB  - Despite evidence of arbovirus activity in northwestern Uganda (West Nile Sub
      region), there is very limited information on the mosquito fauna of this region.
      The only published study reported 52 mosquito species in northwestern Uganda but
      this study took place in 1950 and the information has not been updated for more
      than 60 yr. In January and June 2011, CO2 baited-light traps were used to collect
      49,231 mosquitoes from four different locations, Paraa (9,487), Chobe (20,025),
      Sunguru (759), and Rhino Camp (18,960). Overall, 72 mosquito species representing
      11 genera were collected. The largest number of distinct species was collected at
      Chobe (43 species), followed by Paraa (40), Sunguru (34), and Rhino Camp (25).
      Only eight of the 72 species (11.1%) were collected from all four sites: Aedes
      (Stegomyia) aegypti formosus (Walker), Anopheles (Cellia) funestus group, Culex
      (Culex) decens group, Cx. (Culex) neavei Theobald, Cx. (Culex) univittatus
      Theobald, Cx. (Culiciomyia) cinereus Theobald, Cx. (Oculeomyia) poicilipes
      (Theobald), and Mansonia (Mansonoides) uniformis (Theobald). Fifty-four species
      were detected in northwestern Uganda for the first time; however, these species
      have been detected elsewhere in Uganda and do not represent new introductions to
      the country. Thirty-three species collected during this study have previously
      been implicated in the transmission of arboviruses of public health importance.

PMID- 29444288
TI  - LOB DOMAIN-CONTAINING PROTEIN 15 Positively Regulates Expression of VND7, a
      Master Regulator of Tracheary Elements.
AB  - Xylem includes xylem parenchyma cells, fibers and tracheary elements.
      Differentiation of tracheary elements is an irreversible process that is
      controlled by the master regulator VASCULAR-RELATED NAC-DOMAIN 7 (VND7).
      Molecular events occurring downstream of VND7 are well understood, but little is
      known regarding upstream regulation of VND7. In this study, we identified LOB
      DOMAIN-CONTAINING PROTEIN 15 (LBD15)/ASYMMETRIC LEAVES2-LIKE (ASL11) as a
      regulator of VND7. LBD15 was expressed in immature vascular cells and positively
      regulated both VND7 expression and differentiation of tracheary elements. LBD15
      directly associated with the upstream sequence of VND7 and positively regulated
      VND7 expression. A 25 bp upstream sequence was essential for VND7 expression in
      the elongation zone of Arabidopsis roots. Taken together with previous studies
      identifying LBD15 as a target of VND7, we propose that LBD15 acts in a positive
      feedback regulation system that promotes and accelerates VND7 expression during
      the initiation phase of tracheary element differentiation in roots.

PMID- 29444289
TI  - Knowledge, attitude, and behaviors of health professionals towards smoking
      cessation in primary healthcare settings.
AB  - This study aimed to assess the behaviors of multiple health professionals in
      primary healthcare settings in Jordan towards smoking cessation counseling and to
      determine the barriers to effective smoking cessation behaviors. A survey of 456
      health professionals in primary healthcare settings was conducted. A self
      administrated questionnaire was used to collect the data. About half of health
      professionals reported that they usually ask patients about smoking status and
      advise them to stop smoking (51.4% and 50.5%, respectively). Only 23.7% reported
      assessing the willingness of the patients to quit smoking and 17.9% reported
      discussing counseling options with smokers. Considerably fewer percentages of
      health professionals reported preparing their patients for withdrawal symptoms
      (6.0%), discussing pharmacotherapies (3.8%), and prescribing nicotine patches
      (6.4%). Key barriers to smoking cessation counseling, as reported by health
      professionals, included: insufficient resources and organizational support,
      limited coverage of cessation interventions, and lack of motivation to quit.
      Smoking cessation counseling was not routinely implemented by Jordanian health
      professionals. Barriers to effective delivery of smoking cessation counseling
      need to be integrated within relevant strategies aiming at enhancing the
      frequency and quality of health professionals' engagement in smoking cessation.

PMID- 29444290
TI  - Impact of renal allograft nephrectomy on graft and patient survival following
      retransplantation: a systematic review and meta-analysis.
AB  - Background: It is not clear whether renal allograft removal affects the outcome
      of renal retransplantation. This study aimed to determine the effect of allograft
      nephrectomy (AN) and no-AN (No AN) on renal retransplantation. Methods: A
      systematic review and meta-analysis were conducted using MEDLINE, Embase and the
      Cochrane Library. Observational studies or randomized controlled trials including
      renal retransplantation recipients with AN or No-AN were included. The primary
      outcomes were graft survival, patient survival, acute rejection (AR) and delayed
      graft dysfunction; the secondary outcomes were positive panel reactive antibody
      rate and serum creatinine level at 1 year after retransplantation, cold ischemia
      time and time of hemodialysis before recent transplantation. Pooled estimates of
      odds ratios (ORs) and the weighted mean difference for outcomes were calculated.
      Results: A total of 13 studies divided into 20 trials including 1923 patients
      were analyzed. The No-AN group had a significantly higher 3-year graft survival
      rate {OR 0.48 [95% confidence interval (CI) 0.34-0.69], 10 studies, n = 1030} and
      5-year graft survival rate [OR 0.65 (95% CI 0.44-0.97), 16 studies, n = 1878]
      than the AN group. The rates of 5-year patient survival [OR 1.82 (95% CI 1.14
      2.90), 5 studies, n = 749], positive panel reactive antibody [OR 3.08 (95% CI
      2.08-4.56), 12 studies, n = 1225], AR [OR 1.59 (95% CI 1.21-2.09), 15 studies, n
      = 1388] and delayed graft dysfunction [OR 1.66 (95% CI 1.20-2.03), 8 studies, n =
      879] were all significantly higher in the AN group. Compared with the No-AN
      group, cold ischemia time was longer in the AN group [weighted mean difference
      1.84 (95% CI 0.90-2.79), 7 studies, n = 919]. The rate of 1-year graft survival
      and 10-year graft survival, serum creatinine levels at 1 year after
      retransplantation and the time of hemodialysis before recent transplantation were
      similar between the AN and No-AN groups. Conclusions: We recommend allowing the
      failed graft to remain unless symptoms dictate the need for surgery. We also
      suggest donor-specific antibody dynamic monitoring and better human leukocyte
      antigen matching for improved long-term outcome of retransplantation.

PMID- 29444291
TI  - Novel Sex Chromosomes in 3 Cichlid Fishes from Lake Tanganyika.
AB  - African cichlids are well known for their adaptive radiations, but it is now
      apparent that they also harbor an extraordinary diversity of sex chromosome
      systems. In this study, we sequenced pools of males and females from species in 3
      different genera of cichlids from Lake Tanganyika. We then searched for regions
      that were differentiated following the patterns expected for sex chromosomes. We
      report 2 novel sex chromosomes systems, an XY system on LG19 in Tropheus sp.
      "black" and a ZW system on LG7 in Hemibates stenosoma. We also identify a ZW
      system on LG5 in Cyprichromis leptosoma that may be convergent with a system
      previously described in Lake Malawi cichlids. Our data also identify candidate
      single nucleotide polymorphisms for the blue/yellow tail color polymorphism
      observed among male C. leptosoma.

PMID- 29444293
TI  - The "Som la Pera" intervention: sustainability capacity evaluation of a peer-led
      social-marketing intervention to encourage healthy lifestyles among adolescents.
AB  - Sustainability capacity, always considered a challenge, is the ability to
      maintain effective long-term intervention in a community. The aim of the study
      was to improve the sustainability capacity of effective "Som la Pera," a school
      based, peer-led, social-marketing intervention that encourages healthy diet and
      physical activity, in low socioeconomic adolescents from Spain. The
      sustainability capacity was analyzed by a "programme sustainability assessment
      tool (PSAT)" comprising eight domains: political support, funding stability,
      partnerships, organizational capacity, programme evaluation, programme
      adaptation, communications, and strategic planning. Each domain was evaluated
      from 1 (no or to a small extent) to 7 points (to a great extent). The final score
      for sustainability capacity was the mean of the eight domain scores. The PSAT was
      assessed by nine professionals (researchers, staff members, and stakeholders) at
      two periods during intervention implementation: end of the first year (January
      2015) and end of the second year (September 2015). At the end of the first year,
      strategic planning (4.43 +/- 1.98) and funding stability (4.38 +/- 1) were
      considered deficient domains, and at the end of the second year, these domains
      had improved by 1.67 points (p =.043) and 0.59 points (p = .159), respectively.
      The funding stability increase was not significant because only one of the five
      specific items, "policies implemented to ensure sustained funding," improved by
      1.08 points (p = .036). The sustainability capacity final score was 5.93 +/-
      1.13. The sustainability capacity assessment during the intervention allows its
      improvement before the programme expires, ensuring the long-term implementation
      of the "Som la Pera" intervention programme to encourage healthy lifestyles in
      adolescents.

PMID- 29444294
TI  - Prognosis of adult obstructive hypertrophic cardiomyopathy patients with
      different morphological types after surgical myectomy.
AB  - OBJECTIVES: This study aims to assess the impact of morphological type on the
      prognosis of obstructive hypertrophic cardiomyopathy patients who underwent
      myectomy. METHODS: We recruited 469 obstructive hypertrophic cardiomyopathy
      patients refractory to medicinal treatment who have undergone surgical myectomy
      at a nationwide referral centre. All patients were divided into 3 groups based on
      the morphological classification of left ventricular hypertrophy and were
      followed up by telephone every year. The primary end-points were sudden cardiac
      death, aborted sudden cardiac death and death due to heart failure or stroke. The
      secondary end-points were non-fatal cardiovascular events. RESULTS: Typical
      hypertrophy limited to the basal septum, hypertrophy of the whole ventricular
      septum and hypertrophy that involved the whole left ventricle were presented in
      248 (52.9%), 141 (30.1%) and 80 (17.0%) patients, respectively. During the follow
      up of 2.5 +/- 1.4 years after myectomy, 10 (2.1%) and 43 (9.2%) patients met the
      primary end-point and secondary end-points, respectively. The maximal thickness
      of the ventricular septum, the left ventricular mass and the presence of
      extensive late gadolinium enhancement were lower in patients with hypertrophy
      limited to the basal septum than in other patients. Patients with the basal
      septum hypertrophy showed better survival after myectomy compared with other
      patients. For the secondary and composite end-points, there was no significant
      difference between the 3 groups. CONCLUSIONS: Patients with hypertrophy limited
      to the basal septum represented a special clinical subtype of obstructive
      hypertrophic cardiomyopathy showing better clinical outcomes, while diffuse
      hypertrophy of the ventricular septum and free wall indicated lower survival
      after surgical myectomy.

PMID- 29444292
TI  - Determinants of sleepiness in obstructive sleep apnea.
AB  - Study Objectives: Significant interindividual variability in sleepiness is
      observed in clinical populations with obstructive sleep apnea (OSA). This
      phenomenon is only partially explained by the apnea-hypopnea index (AHI).
      Understanding factors that lead to sleepiness is critical to effective management
      of patients with OSA. We examined demographic and other factors associated with
      sleepiness in OSA. Methods: Prospective study of 283 patients with newly
      diagnosed OSA by polysomnography (AHI >= 5 per hour). Subjective sleepiness
      (Epworth Sleep Scale [ESS] >= 11) and objective sleepiness (psychomotor vigilance
      task [PVT] mean lapse >= 2) were assessed. Results: Participants were classified
      into four groups (1: sleepy by ESS and PVT, 2: sleepy by PVT only, 3: sleepy by
      ESS only, and 4: nonsleepy reference group) and compared by generalized logit
      model. Shorter daily sleep duration by actigraphy and less morningness were
      associated with higher risk of sleepiness (Odds ratio [OR] = 0.52, 95% confidence
      interval [CI] 0.33-0.82 and OR = 0.89, CI 0.80-0.98, respectively). African
      American race was associated with sleepiness (group 1, OR = 8.8, CI 2.8-27.3;
      group 2, OR = 16.6, CI 3.3-83.6; and group 3, OR = 3.3, CI 1.0-10.1). IL-6 level
      was higher in groups 1 and 3 (OR = 1.9, CI 1.0-3.4 and OR 2.0, CI 1.1-3.7,
      respectively). Conclusions: African-American race, short sleep duration,
      chronotype, and increased proinflammatory cytokine IL-6 level were associated
      with sleepiness in OSA. These findings will inform future investigations
      determining mechanisms of sleepiness in OSA.

PMID- 29444295
TI  - Conus Medullaris Dural Arteriovenous Fistula Arising From the Artery of the Filum
      Terminale: 2-Dimensional Operative Video.

PMID- 29444296
TI  - A Longitudinal Study of Depressive Symptoms, Neuropsychological Functioning, and
      Medical Responsibility in Youth With Spina Bifida: Examining Direct and Mediating
      Pathways.
AB  - Objective: Given the increased risk for cognitive deficits and development of
      depressive symptoms in youth with spina bifida (SB), this study aimed to examine
      two pathways through which depressive symptoms and neuropsychological dysfunction
      may be associated with medical autonomy in this population: (1) depressive
      symptoms as predictors of medical autonomy as mediated by attention/executive
      functioning (the cognitive scarring model), and (2) attention/executive
      functioning as predictors of medical autonomy as mediated by depressive symptoms
      (the cognitive vulnerability model). Methods: Participants were recruited as part
      of a larger, longitudinal study, and included 114 youth with SB (M age = 10.96 at
      Time 1), their parents, and teachers. Neuropsychological constructs included
      attention, working memory, and planning/organizing abilities, which were measured
      with questionnaire and performance-based data. Depressive symptoms and medical
      responsibility were assessed via questionnaires from multiple respondents.
      Results: Bootstrapped mediation analyses revealed that teacher-reported
      depressive symptoms significantly mediated the relations between
      neuropsychological functioning (i.e., attention and working memory) and medical
      responsibility (all p's < .05); neuropsychological dysfunction did not mediate
      the relationship between depressive symptoms and medical responsibility.
      Conclusions: One way in which neurocognitive dysfunction may hinder the
      development of medical autonomy in youth with SB is through an increased risk for
      depressive symptoms.

PMID- 29444298
TI  - Resection of Petroclival Meningioma Through Retrosigmoid Approach-Concepts and
      Nuances: 3- Dimensional Operative Video.

PMID- 29444297
TI  - Draft genomes of two blister beetles Hycleus cichorii and Hycleus phaleratus.
AB  - Background: Commonly known as blister beetles or Spanish fly, there are more than
      1500 species in the Meloidae family (Hexapoda: Coleoptera: Tenebrionoidea) that
      produce the potent defensive blistering agent cantharidin. Cantharidin and its
      derivatives have been used to treat cancers such as liver, stomach, lung, and
      esophageal cancers. Hycleus cichorii and Hycleus phaleratus are the most
      commercially important blister beetles in China due to their ability to
      biosynthesize this potent vesicant. However, there is a lack of genome reference,
      which has hindered development of studies on the biosynthesis of cantharidin and
      a better understanding of its biology and pharmacology. Results: We report 2
      draft genomes and quantified gene sets for the blister beetles H. cichorii and H.
      phaleratus, 2 complex genomes with >72% repeats and approximately 1%
      heterozygosity, using Illumina sequencing data. An integrated assembly pipeline
      was performed for assembly, and most of the coding regions were obtained.
      Benchmarking universal single-copy orthologs (BUSCO) assessment showed that our
      assembly obtained more than 98% of the Endopterygota universal single-copy
      orthologs. Comparison analysis showed that the completeness of coding genes in
      our assembly was comparable to other beetle genomes such as Dendroctonus
      ponderosae and Agrilus planipennis. Gene annotation yielded 13 813 and 13 725
      protein-coding genes in H. cichorii and H. phaleratus, of which approximately 89%
      were functionally annotated. BUSCO assessment showed that approximately 86% and
      84% of the Endopterygota universal single-copy orthologs were annotated
      completely in these 2 gene sets, whose completeness is comparable to that of D.
      ponderosae and A. planipennis. Conclusions: Assembly of both blister beetle
      genomes provides a valuable resource for future biosynthesis of cantharidin and
      comparative genomic studies of blister beetles and other beetles.

PMID- 29444299
TI  - Early Nodal and Paranodal Disruption in Autoimmune Optic Neuritis.
AB  - Disturbances in the nodes of Ranvier are an early phenomenon in many CNS
      disorders, including the autoimmune demyelinating disease multiple sclerosis
      (MS). Using an animal model of optic neuritis, a common early symptom of MS, we
      have investigated nodal and paranodal compartments in the optic nerve during
      disease progression. Both nodes and paranodes, as identified by
      immunohistochemistry against sodium channels (Nav) and Caspr, respectively, were
      observed to increase in length during the late induction phase of the disease,
      prior to onset of the demyelination and immune cell infiltration characteristic
      of optic neuritis. These changes were correlated with both axonal stress and
      microglial/macrophage activation, and were most apparent in the vicinity of the
      retrobulbar optic nerve head, the unmyelinated region of the optic nerve where
      retinal ganglion cell axons exit the retina. Using intravitreal glutamate
      injection as a model of a primary retinal insult, we demonstrate that this can
      induce similar nodal and paranodal changes. This may suggest that onset of
      neurodegeneration in the absence of demyelination, as reported in several studies
      into the nonaffected eyes of MS patients, may give rise to subtle disturbances in
      the axo-glial junction.

PMID- 29444300
TI  - Deep Brain Stimulation for Parkinson Disease Does not Worsen or Improve Postural
      Instability: A Prospective Cohort Trial.
AB  - BACKGROUND: Falls and postural instability (PI) are major sources of morbidity in
      Parkinson disease (PD). Deep brain stimulation (DBS) is a major therapy for PD.
      The effects of DBS on PI and falls remain controversial. OBJECTIVE: To study if
      DBS worsens PI, validated measures of PI (Timed Up and Go, Berg Balance Scale,
      Unified Parkinson's Disease Rating Scale 3.12 [Pull Test], and the Biodex Sway
      Index with eyes closed on a firm and soft surface) and reported falls were used
      to prospectively evaluate the effect of DBS on PI at 3 and 12 mo postoperatively
      compared to baseline measurements. The primary outcomes were a positive result on
      4 out of the 5 PI tests and falls. METHODS: Patients presenting for DBS were
      prospectively enrolled and evaluated at presentation and, 3 and 12 mo
      postoperatively. All tests were performed at each visit. RESULTS: At 3 mo 4 of 5
      positive showed noninferiority to baseline, with a rate of 28% vs 41% (relative
      risk [RR] 0.8 [0.5-1.3]). At 12 mo, 4 of 5 positive had a rate of 35% vs 30% (RR
      1.2 [0.8-1.8]) and falls had a rate of 54% vs 46% (RR 1.2 [0.6-2.3]). These did
      not meet criteria to prove noninferiority. Sensitivity analysis at 12 mo showed
      noninferiority for 4 of 5 (RR 0.9 [0.6-1.5]) but not falls (RR 1.1 [0.5-2.3]).
      CONCLUSION: This evidence is consistent with the hypothesis that DBS does not
      worsen PI when measured at 3 and 12 mo postoperatively.

PMID- 29444301
TI  - An integrative review exploring black men of African and Caribbean backgrounds,
      their fears of prostate cancer and their attitudes towards screening.
AB  - Evidence suggests that black men are disproportionately more affected than any
      other ethnicity by prostate cancer. The aim of this review is to identify studies
      exploring black men of African and Caribbean descent, their fears of prostate
      cancer and their attitudes towards screening. Four databases were searched and
      reference lists of relevant papers were hand searched. The inclusion criteria
      were studies exploring attitudes towards screening and fear of prostate cancer in
      black men of African and Caribbean backgrounds, peer-reviewed research,
      qualitative studies, surveys, questionnaires and English language publications.
      Qualitative findings were synthesized using a thematic framework to which
      quantitative findings were integrated. Of the 16 papers, 10 were quantitative and
      6 were qualitative, all of which were conducted in the United States of America.
      Poorer and less educated black men were reluctant to seek help for prostate
      cancer. They may not visit their doctors for fear of intrusion into their
      personal lives. Moreover, they were fearful of being emasculated as a result of
      the digital rectal examination. The review identifies a paucity of UK literature
      on black men's fears and perceptions of prostate cancer. Further studies are
      needed in the United Kingdom to address this gap in the literature.

PMID- 29444302
TI  - RAB GTPases in the Basal Land Plant Marchantia polymorpha.
AB  - The RAB GTPase is an evolutionarily conserved machinery component of membrane
      trafficking, which is the fundamental system for cell viability and higher order
      biological functions. The composition of RAB GTPases in each organism is closely
      related to the complexity and organization of the membrane trafficking pathway,
      which has been developed uniquely to realize the organism-specific membrane
      trafficking system. Comparative genomics has suggested that terrestrialization
      and/or multicellularization were associated with the expansion of membrane
      trafficking pathways in green plants, which has yet to be validated in basal land
      plant lineages. To obtain insight into the diversification of membrane
      trafficking systems in green plants, we analyzed RAB GTPases encoded in the
      genome of the liverwort Marchantia polymorpha in a comprehensive manner. We
      isolated all genes for RAB GTPases in Marchantia and analyzed their expression
      patterns and subcellular localizations in thallus cells. While a majority of
      MpRAB GTPases exhibited a ubiquitous expression pattern, specific exceptions were
      also observed; MpRAB2b, which contains a sequence similar to an intraflagellar
      transport protein at the C-terminal region; and MpRAB23, which has been
      secondarily lost in angiosperms, were specifically expressed in the male
      reproductive organ. MpRAB21, which is another RAB GTPase whose homolog is absent
      in Arabidopsis, exhibited endosomal localization with RAB5 members in Marchantia.
      These results suggest that Marchantia possesses unique membrane trafficking
      pathways involving a unique repertoire of RAB GTPases.

PMID- 29444303
TI  - The Utility of Vancomycin Powder in Reducing Surgical Site Infections in Deep
      Brain Stimulation Surgery.
AB  - BACKGROUND: The impact of vancomycin powder on reducing postoperative surgical
      site infections (SSIs) in spine surgery has been studied extensively and is
      considered standard of care at many institutions. More recently, vancomycin
      powder has been shown to reduce SSI in cranial neurosurgery; however, limited
      studies have been performed assessing its impact in reducing SSIs in deep brain
      stimulation (DBS) surgery. OBJECTIVE: To investigate the use of vancomycin powder
      as an adjunct to the current antibiotic prophylaxis regimen in DBS surgery in a
      large cohort of patients. METHODS: All patients undergoing DBS-lead implantation
      surgery and chest generator placement or exchange were analyzed prior to and
      after the implementation of intrawound vancomycin powder, and the impact on
      infection rate and any complications were subsequently examined. RESULTS: From
      2015 to 2017, a total of 419 consecutive patients (159 in the pretreatment group,
      260 in the post-treatment group) were included in the study. The rate of SSI
      prior to implementation of intrawound vancomycin was 3.1% (n = 5), which was
      reduced to 0.38% (n = 1) in the post-treatment group. No complications were noted
      as a direct result of using vancomycin powder. CONCLUSION: Given its relatively
      low cost and side effect profile, the use of vancomycin powder may be an
      effective adjunct in reducing the rate of SSI in DBS surgery.

PMID- 29444304
TI  - Devolution and the regional health divide: a longitudinal ecological study of 14
      countries in Europe.
AB  - Background: Greater regional devolution can reduce economic inequalities between
      regions; however, the impact on health inequalities is not clear. We investigated
      the association between changes over time in the level of devolution in European
      countries and regional economic and health inequalities. Methods: We used the
      proportion of government expenditure controlled by subnational levels of
      government as our measure of devolution in 14 European countries between 1995 and
      2011. Fixed effects linear regression models were used to analyse trends in the
      level of devolution, trends in regional economic inequalities (Gini-coefficient)
      and trends in regional health inequalities (slope index) in life expectancy.
      Results: Each additional percentage of government expenditure managed at
      subnational level reduced the Gini-coefficient of regional GDP by -0.17 points
      (95% CI: -0.33 to -0.01; P = 0.04). However, it increased the slope index of
      regional life expectancy by 23 days (95% CI: -2 to 48; P = 0.07). When trends in
      regional economic inequalities were controlled for, as a potential mediator
      increased devolution-was significantly associated with an increase in health
      inequalities between regions (P = 0.01). Conclusions: Increased devolution does
      not appear to reduce regional health inequalities-even when it reduces regional
      economic inequalities-and it could be associated with increased health
      inequalities.

PMID- 29444305
TI  - Poor palatability of the new ritonavir formulation is a major obstacle to
      adherence to treatment in young children.

PMID- 29444306
TI  - MpAMT1;2 from Marchantia polymorpha is a High-Affinity, Plasma Membrane Ammonium
      Transporter.
AB  - Plant ammonium transporters in the AMT/MEP/Rh (ammonium
      transporter/methylammonium and ammonium permease/Rhesus factor) superfamily have
      only been previously characterized in flowering plants (angiosperms). Plant AMT1s
      are electrogenic, while plant AMT2s are electroneutral, and MEP and Rh
      transporters in other organisms are electroneutral. We analyzed the transport
      function of MpAMT1;2 from the basal land plant Marchantia polymorpha, a
      liverwort. MpAMT1;2 was shown to localize to the plasma membrane in Marchantia
      gametophyte thallus by stable transformation using a C-terminal citrine fusion.
      MpAMT1;2 expression was studied using quantitative real-time PCR and shown to be
      higher when plants were N deficient and lower when plants were grown on media
      containing ammonium, nitrate or the amino acid glutamine. Expression in Xenopus
      oocytes and analysis by electrophysiology revealed that MpAMT1;2 is an
      electrogenic ammonium transporter with a very high affinity for ammonium (7 uM at
      pH 5.6 and a membrane potential of -137 mV). A conserved inhibitory
      phosphorylation site identified in angiosperm AMT1s is also present in all AMT1s
      in Marchantia. Here we show that a phosphomimetic mutation T475D in MpAMT1;2
      completely inhibits ammonium transport activity. The results indicate that
      MpAMT1;2 may be important for ammonium uptake into cells in the Marchantia
      thallus.

PMID- 29444307
TI  - Senescence and nitrogen use efficiency in perennial grasses for forage and
      biofuel production.
AB  - Organ senescence is an important developmental process in plants that enables
      recycling of nutrients, such as nitrogen, to maximize reproductive success.
      Nitrogen is the mineral nutrient required in greatest amount by plants, although
      soil-N limits plant productivity in many natural and agricultural systems,
      especially systems that receive little or no fertilizer-N. Use of industrial N
      fertilizers in agriculture increased crop yields several fold over the past
      century, although at substantial cost to fossil energy reserves and the
      environment. Therefore, it is important to optimize nitrogen use efficiency (NUE)
      in agricultural systems. Organ senescence contributes to NUE in plants and
      manipulation of senescence in plant breeding programs is a promising approach to
      improve NUE in agriculture. Much of what we know about plant senescence comes
      from research on annual plants, which provide most of the food for humans.
      Relatively little work has been done on senescence in perennial plants,
      especially perennial grasses, which provide much of the forage for grazing
      animals and promise to supply much of the biomass required by the future biofuel
      industry. Here, we review briefly what is known about senescence from studies of
      annual plants, before presenting current knowledge about senescence in perennial
      grasses and its relationship to yield, quality, and NUE. While higher yield is a
      common target, desired N-content diverges between forage and biofuel crops. We
      discuss how senescence programs might be altered to produce high-yielding, stress
      tolerant perennial grasses with high-N (protein) for forage or low-N for biofuels
      in systems optimized for NUE.

PMID- 29444308
TI  - Integration of multi-omics techniques and physiological phenotyping within a
      holistic phenomics approach to study senescence in model and crop plants.
AB  - The study of senescence in plants is complicated by diverse levels of temporal
      and spatial dynamics as well as the impact of external biotic and abiotic factors
      and crop plant management. Whereas the molecular mechanisms involved in
      developmentally regulated leaf senescence are very well understood, in particular
      in the annual model plant species Arabidopsis, senescence of other organs such as
      the flower, fruit, and root is much less studied as well as senescence in
      perennials such as trees. This review addresses the need for the integration of
      multi-omics techniques and physiological phenotyping into holistic phenomics
      approaches to dissect the complex phenomenon of senescence. That became feasible
      through major advances in the establishment of various, complementary 'omics'
      technologies. Such an interdisciplinary approach will also need to consider
      knowledge from the animal field, in particular in relation to novel regulators
      such as small, non-coding RNAs, epigenetic control and telomere length. Such a
      characterization of phenotypes via the acquisition of high-dimensional datasets
      within a systems biology approach will allow us to systematically characterize
      the various programmes governing senescence beyond leaf senescence in Arabidopsis
      and to elucidate the underlying molecular processes. Such a multi-omics approach
      is expected to also spur the application of results from model plants to
      agriculture and their verification for sustainable and environmentally friendly
      improvement of crop plant stress resilience and productivity and contribute to
      improvements based on postharvest physiology for the food industry and the
      benefit of its customers.

PMID- 29444309
TI  - Plant senescence: how plants know when and how to die.

PMID- 29444310
TI  - RADIOLOGICAL HAZARD INDICES OF GRANITIC ROCKS USED FOR THE CONSTRUCTION OF
      BUILDINGS FROM NUBA MOUNTAINS SUDAN.
AB  - This study was conducted to assess the level of radioactivity and the radiation
      hazards associated with granite rocks used for construction of buildings. The
      measurement of radioactivity content of the rock samples was performed with gamma
      spectrometry equipped with Nal (TI) detector. From the results obtained in this
      study the average activity concentrations of 226Ra, 232Th and 40K were 20.64,
      30.50 and 295.19 Bq kg-1, respectively. The absorbed dose rate in air at 1 m
      above ground level, the annual effective dose and the gamma index were determined
      with the aim to assess the possible radiological impact on inhabitants of
      dwellings built using such rocks. The mean value of the absorbed dose rate, the
      annual effective dose and the gamma index (Igamma) was 36.36 nGy h-1, 40.79 MUSv
      y-1 and 0.51 MUSv y-1, respectively. Radium equivalent activities, and external
      and internal hazard indices, were also calculated. These data indicated that the
      area of study lies within areas recognized as normal background radiation and the
      granite rocks are safe to be used as building material and other structural
      purposes.

PMID- 29444311
TI  - Income inequality and self-reported health in a representative sample of 27 017
      residents of state capitals of Brazil.
AB  - Background: The association between income inequality and health has been
      analyzed predominantly in developed countries with modest levels of inequality.
      The study aimed to analyze the association between income inequality and self
      reported health (SRH) in the adult population of the 27 Brazilian capitals.
      Methods: Individuals aged 18 years or older from the National Health survey
      residing in Brazilian capitals in 2013 were analyzed (n = 27 017). Bayesian
      multilevel models were applied after controlling for individual factors and area
      level socioeconomic characteristics. Results: We found a significant association
      between income inequality and SRH, even after controlling for individual and
      contextual factors. The results indicate greater odds of poor SRH among those
      living in areas with medium (OR = 1.31, 95% CI: 1.17-1.47) and high income
      inequality level (OR = 1.39, 95% CI: 1.24-1.56). Income inequality remained
      significantly associated with SRH, even after controlling for other contextual
      socioeconomic characteristics, such as local illiteracy rate, violence and per
      capita income. Conclusions: The study highlights the importance of the individual
      and contextual characteristics associated with SRH. Our findings suggest that
      city-level income inequality can have a detrimental effect on individual health,
      over and above other contextual socioeconomic characteristics and individual
      factors.

PMID- 29444313
TI  - Predictive biomarkers and EGFR inhibitors in squamous cell carcinoma of head and
      neck (SCCHN).

PMID- 29444312
TI  - In Concert: Orchestrated Changes in Carbohydrate Homeostasis Are Critical for
      Plant Abiotic Stress Tolerance.
AB  - The sessile lifestyle of higher plants is accompanied by their remarkable ability
      to tolerate unfavorable environmental conditions. This is because, during
      evolution, plants developed a sophisticated repertoire of molecular and metabolic
      reactions to cope with changing biotic and abiotic challenges. In particular, the
      abiotic factors light intensity and ambient temperature are characterized by
      altering their amplitude within comparably short periods of time and are
      causative for onset of dynamic plant responses. These rapid responses in plants
      are also classified as 'acclimation reactions' which differ, due to their
      reversibility and duration, from non-reversible 'adaptation reactions'. In this
      review, we demonstrate the remarkable importance of stress-induced changes in
      carbohydrate homeostasis of plants exposed to high light or low temperatures.
      These changes represent a co-ordinated process comprising modifications of (i)
      the concentrations of selected sugars; (ii) starch turnover; (iii) intracellular
      sugar compartmentation; and (iv) corresponding gene expression patterns. The
      critical importance of these individual processes has been underlined in the
      recent past by the analyses of a large number of mutant plants. The outcome of
      these analyses raised our understanding of acclimation processes in plants per se
      but might even become instrumental to develop new concepts for directed breeding
      approaches with the aim to increase abiotic stress tolerance of crop species,
      which in most cases have high stress sensitivity. The latter direction of plant
      research is of special importance since abiotic stress stimuli strongly impact on
      crop productivity and are expected to become even more pronounced because of
      human activities which alter environmental conditions rapidly.

PMID- 29444314
TI  - Diffuse Astrocytoma, IDH-Wildtype: A Dissolving Diagnosis.
AB  - The histological and molecular features and even the mere existence of diffuse
      astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse
      astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry
      followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status
      and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip.
      Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and
      without contrast enhancement. By DNA methylation profiling, 10/25 tumors were
      classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be
      classified using methylome analysis, but showed genetic characteristics of
      glioblastoma. Histologically, all of these 17 tumors were low-grade diffuse
      astrocytomas. Nevertheless, 10/17 patients experienced early malignant
      progression. Other methylation classes included diffuse midline glioma, H3 K27M
      mutant, diffuse astrocytoma, IDH-mutant, pilocytic astrocytoma, and normal or
      reactive brain tissue (total n = 8). In conclusion, no convincing diffuse
      astrocytoma, IDH-wildtype, was identified. Most IDH-wildtype tumors showing
      histopathological and radiological features of low-grade diffuse astrocytoma
      exhibit molecular and clinical features of high-grade glioma and may represent an
      early stage of primary glioblastoma. Our findings have implications for the
      biology, classification and neuropathological diagnosis of diffuse astrocytoma,
      IDH-wildtype in adults.

PMID- 29444315
TI  - MEASUREMENT OF INTERNAL RADIATION DOSE DISTRIBUTION IN CT EXAMINATIONS USING
      POLYETHYLENE TEREPHTHALATE RESIN.
AB  - This study proposes a new dosimetry method for the estimation of the internal
      radiation dose distribution of a subject undergoing computed tomography (CT)
      examinations. In this novel method, dose distribution of a subject by CT scans
      was estimated based on radiophotoluminance distribution with polyethylene
      terephthalate (PET) resin which was cut to the average head size of a Japanese 1
      year-old child. The difference in dose distribution depending on the type of
      bowtie filter was visualized by imaging luminance distribution with the PET
      phantom using a charge-coupled device camera. Dose distribution images simulated
      from a water phantom of the same size as the PET phantom were compared with the
      luminance distribution images. The linear correlation was demonstrated between
      luminance of the PET phantom and the simulated water dose. In comparison with the
      simulated water doses and the converted water doses from luminance of the PET
      phantom, the relative differences were within 20%.

PMID- 29444317
TI  - Melanization of a meristematic mutant of Fonsecaea monophora increase the
      pathogenesis in a BALB/c mice infection model.
AB  - The role of melanin in agents of chromoblastomycosis in vivo still remains
      unclear. In this study, we addressed the question in a BALB/c mice infection
      model by using an albino mutant, which generated from a melanized meristematic
      mutant of F. monophora. The most severe clinical manifestations of infected mice
      were observed at 10-25 dpi (day post infection) and 7-15 dpi for melanized and
      albino strain, respectively. Histopathologic examination were similar in both
      groups at 15 dpi (acute infection phase), but not at 30 dpi (sustained infection
      phase) and 45 dpi (recovery phase). Sclerotic body could be revealed in melanized
      strain infection group compare with albino strain infection group at 45 dpi. We
      found significantly elevated of TH2 cytokines in melanized strain infected group
      at 15 dpi, while increased expression level of TH1 and TH17 cytokines in albino
      strain infection group at 15 and 30 dpi. In conclusion, the present data
      addressed our speculation that melanization of this meristematic mutant of F.
      monophora could increase the pathogenesis in vivo. The inhibition of TH1 and
      TH17, exacerbated TH2 ability of melanized F. monophora is the key to escape the
      host immune system at the initial recognition and persistence in BALB/c mice.

PMID- 29444318
TI  - Comment on: Managing varicella zoster virus contact and infection in patients on
      anti-rheumatic therapy.

PMID- 29444316
TI  - Glucose triggers stomatal closure mediated by basal signaling through HXK1 and
      PYR/RCAR receptors in Arabidopsis.
AB  - Sugars play important roles in regulating plant growth, development, and stomatal
      movement. Here, we found that glucose triggered stomatal closure in a dose- and
      time-dependent manner in Arabidopsis. Pharmacological data showed that glucose
      induced stomatal closure was greatly inhibited by catalase [CAT; a reactive
      oxygen species (ROS) scavenger], diphenyleneiodonium chloride (DPI; an NADPH
      oxidase inhibitor), lanthanum chloride (LaCl3; a Ca2+ channel blocker), EGTA (a
      Ca2+ chelator), and two nitrate reductase (NR) inhibitors, tungstate and sodium
      azide (NaN3), while it was not affected by salicylhydroxamic acid (SHAM; a
      peroxidase inhibitor). Moreover, glucose induced ROS and nitric oxide (NO)
      production in guard cells of Arabidopsis. The ROS production was almost
      completely removed by CAT, strongly restricted by DPI, and was not affected by
      SHAM. NO production was partially suppressed by tungstate and NaN3, and the
      levels of NO were significantly reduced in the nia1-1nia2-5 mutant. Additionally,
      glucose-triggered stomatal closure was significantly impaired in gin1-1, gin2-1,
      pyr1pyl1pyl2pyl4, abi1-1, ost1, slac1-4, cpk6-1, and nia1-1nia2-5 mutants.
      Likewise, the reductions in leaf stomatal conductance (gs) and transpiration rate
      (E) caused by glucose were reversed in the above mutants. These results suggest
      that glucose-triggered stomatal closure may be dependent on basal signaling
      through PYR/RCAR receptors and hexokinase1 (HXK1).

PMID- 29444319
TI  - Beneficial effects of water-soluble chestnut (Castanea sativa Mill.) tannin
      extract on chicken small intestinal epithelial cell culture.
AB  - Feed and water supplementation with powdered hydrolyzable tannins from chestnut
      represents a valuable alternative strategy to antibiotics in animal nutrition. In
      this study, we evaluated the effects and safety of a water-soluble form of
      chestnut tannin (WST) in an in vitro model of chicken small intestinal epithelial
      cells (CSIEC). A chicken cell culture was established, and WST in concentrations
      of 0.025, 0.05, 0.1, and 0.2% were tested for cytotoxicity, cell proliferation,
      metabolic activity, production of reactive oxygen species, intracellular
      antioxidative potential, genotoxicity, and influence on the epithelia cell cycle.
      The tested concentrations showed a significant (P < 0.05) greater proliferative
      effect on CSIEC than the control medium (maximal proliferation at 0.1% WST as
      determined by optical density measurements). The 0.2% concentration of WST was
      cytotoxic, causing significantly higher (P < 0.05) nitric oxide and hydrogen
      peroxide production but with no short-term genotoxicity. Although increasing the
      concentration caused a decline in the metabolism of challenged cells (the lowest
      at 0.1% WST), metabolic activity remained higher than that in control cells. The
      antioxidant potential was 75% better and significantly (P < 0.05) higher in the
      0.1% WST cultured cells compared to control. In conclusion, the cultured CSIEC
      are useful tools in basic and clinical research for the study of intestinal
      physiology, as they retain physiological and biochemical properties and
      epithelial morphology close to the original tissue and, in many ways, reflect the
      in vivo state. Our results indicate that WST exert a beneficial effect on
      intestinal epithelia, since they: i) stimulate proliferation of enterocytes; ii)
      increase antioxidative potential; iii) have no genotoxic effect; and iv) do not
      affect cellular metabolism. Our results reinforce the importance of WST as
      promising candidates for further evaluation and use in commercial broiler farm
      production.

PMID- 29444320
TI  - Effect of phytase on growth performance, phytate degradation and gene expression
      of myo-inositol transporters in the small intestine, liver and kidney of 21 day
      old broilers.
AB  - An experiment was conducted to evaluate phytase supplementation on growth,
      phytate degradation, and the gene expression of myo-inositol transporters in 21
      day old broilers. Ross 308, male broilers (n = 240) were assigned to one of four
      diets, with 10 pens/diet and six birds/pen from day one to 21. The diets
      consisted of a negative control (NC) formulated to meet or exceed Ross 308
      nutrient requirements, with the exception of calcium (Ca) and available P (avP),
      which were reduced by 0.16 and 0.15%, respectively. The NC diet was supplemented
      with 0, 500, 1,500, or 4,500 units/kg of phytase (FTU) to create four
      experimental diets. On day 21, all birds per pen were euthanized to obtain
      digesta and tissue samples for phytate degradation and gene expression. Data were
      analyzed as an analysis of variance using the fit model platform in JMP v 13.0.
      The model included phytase and significant means were separated using orthogonal
      linear and quadratic contrasts. Phytase supplementation increased gain (linear, P
      < 0.05). Phytate (iP6; quadratic, P < 0.05), phytate ester (iP5, iP4, iP3;
      quadratic, P < 0.05), and inositol (linear, P < 0.05) concentration in the
      gizzard was influenced by phytase supplementation. Phytate concentration
      decreased (linear, P < 0.05), iP5 or iP4 concentration increased and then
      decreased (quadratic, P < 0.05), and inositol concentration increased (quadratic,
      P < 0.05) in the ileal digesta as phytase supplementation increased in the diet.
      There was a tendency for the gene expression of the H+-dependent myo-inositol
      transporter, HMIT, to increase (linear, P < 0.05) in the ileum as phytase dose
      increased. Gene expression of the sodium-dependent myo-inositol transporter,
      SMIT2, increased in the jejunum (quadratic, P < 0.05) as phytase dose increased.
      Intestinal alkaline phosphatase expression increased (linear, P < 0.05) in the
      ileum as phytase supplementation increased in the diet. The influence of phytase
      on phytate, phytate esters, and inositol may influence intestinal alkaline
      phosphatase activity and the gene expression of myo-inositol transporters in the
      small intestine.

PMID- 29444321
TI  - Left ventricular regional dyssynchrony predicts improvements in moderate
      ischaemic mitral regurgitation after off-pump coronary artery bypass.
AB  - OBJECTIVES: The aim of this study was to explore the predictors of the
      improvement in moderate ischaemic mitral regurgitation (IMR) after off-pump
      coronary artery bypass grafting (OPCAB) focusing on left ventricular (LV)
      dyssynchrony. METHODS: A prospective study was performed among 135 patients (age
      at surgery, mean +/- SD: 67.0 +/- 8.2 years, 33.3% women) with prior myocardial
      infarction and moderate IMR undergoing OPCAB from 2008 to 2015. Preoperative and
      follow-up clinical and echocardiographic parameters were analysed, focusing on LV
      global/regional dyssynchrony. Patients were grouped by IMR at 1 year
      postoperatively: improved group with no or mild IMR (n = 61) and failure group
      with moderate or severe IMR (n = 67). Data were compared between groups to
      explore the predictors of IMR improvement after OPCAB. RESULTS: Seven patients
      who died before the 1-year postoperative assessment were excluded. At the 1-year
      follow up, there were 61 patients in the improved group and 67 patients in the
      failure group. Preoperatively, the improved group had smaller LV global
      dyssynchrony, LV regional dyssynchrony (papillary muscle systolic dyssynchrony;
      improved group versus failure group: 48.5 +/- 4.5 ms vs 57.1 +/- 3.9 ms; P <
      0.001) and greater LV ejection fraction (improved group versus failure group:
      44.7 +/- 5.0% vs 36.7 +/- 6.7%; P < 0.001) than the failure group. Papillary
      muscle systolic dyssynchrony (odds ratio 1.556, 95% confidence interval 1.313
      1.845; P < 0.001) and preoperative ejection fraction (odds ratio 0.799, 95%
      confidence interval 0.691-0.924; P = 0.002) were independent predictors of
      moderate IMR improvement after OPCAB. CONCLUSIONS: In the selected patients,
      preoperative moderate IMR could be relieved by coronary artery bypass grafting.
      Greater ejection fraction and absence of LV regional dyssynchrony may predict the
      improvement in moderate IMR after coronary artery bypass grafting, suggesting
      that LV dyssynchrony especially regional dyssynchrony and preserved ventricular
      function would be important to the outcome of patients with moderate IMR.

PMID- 29444322
TI  - Physiological reactions to long-term fishing in the Barents Sea.
AB  - Background: Fishing in distant waters for months may induce physiological stress.
      Aims: To assess the physiological stress reactions in fishermen working for 2-3
      months continuously in 6-h shifts on trawlers in the Barents Sea. Methods: The
      crew of five trawlers fishing in the Barents Sea from January to April 2004 were
      invited to participate. In the week before and 5-7 days after the trip, the
      following measures were collected: salivary cortisol four times a day, 24-h
      urinary cortisol, blood pressure, heart rate, serum cholesterol, serum high
      density lipoprotein (HDL-cholesterol), HbA1c (glycosylated haemoglobin) and
      weight. In addition, 24-h urinary cortisol, blood pressure and heart rate were
      measured three times. A questionnaire on health, social conditions and work
      environment was obtained after the trip. Results: In total, 136 men agreed to
      participate. Full data were obtained for 96 fishermen (70%). A significant
      decrease in salivary and urinary cortisol was found during the trip. Adjustment
      for age, body mass index, smoking, shift work schedule and time of day for sample
      collection did not change this finding. Systolic and diastolic blood pressure
      declined significantly and remained significantly lower after the trip compared
      to before the trip. Serum cholesterol/HDL ratio declined significantly, whereas
      triglycerides, HbA1c and weight were unchanged. Conclusions: Working up to 3
      months on 6-h shifts, 84 h a week, with moderate physical activity, even in
      artificial light and cold weather on a ship, did not result in increased
      physiological stress.

PMID- 29444323
TI  - The role of fat and inflammation in the pathogenesis and management of
      osteoarthritis.
AB  - OA is a complex disease involving mechanical, metabolic and inflammatory
      contributions to its aetiology. A key risk factor, obesity, is becoming an
      increasing focus of research due to its multiple potential impacts on OA
      incidence, progression and symptom severity. An increased load due to an increase
      in body mass has been well established as a mechanical contribution to the
      pathophysiology of OA. However, evidence of obesity-linked to OA in non-weight
      bearing joints has implicated the biological role of adipose inflammation and
      metabolic abnormalities in OA. The identification of inflammatory mediators such
      as adipokines (adipose-derived molecules) in OA has further incriminated the role
      of adiposity. This narrative review aims to discuss the role of adipose-derived
      inflammation in OA, with a focus on the contrast between systemic and local
      adipose tissue, and potential treatment applications targeting the adipo
      inflammatory aspects of the disease.

PMID- 29444324
TI  - Neuro-Behcet's disease in a patient with thrombotic thrombocytopenic purpura.

PMID- 29444325
TI  - Evaluation of the dissemination of SNaX, a middle school-based obesity prevention
      intervention, within a large US school district.
AB  - Few evidence-based school obesity-prevention programs are disseminated. We used
      community-based participatory research principles to disseminate an evidence
      based middle-school obesity-prevention program, Students for Nutrition and
      eXercise (SNaX), to a large, primarily Latino, school district. In the 2014-2015
      school year, we trained a district "champion" to provide training and technical
      assistance to schools and supplied print- and web-based materials
      (www.snaxinschools.org). In one district region, 18 of 26 schools agreed to
      participate. We evaluated the dissemination process using the Reach,
      Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. All
      18 schools implemented at least one SNaX component. Of 6,410 students who
      attended an informational session, 1,046 registered and 472 were selected to be
      Student Advocates, of whom 397 attended at least one meeting. Of 60 activities
      observed across schools, 77% were conducted with fidelity, but local resource
      constraints limited most activities to a relatively small number of Student
      Advocates (vs. the entire student body). Qualitative data from 46 school staff
      and 187 students indicated positive attitudes about the program. Teachers
      suggested that SNaX be implemented as part of the curriculum. In the 2015-2016
      school year, 6 of the original schools continued to implement SNaX, and the
      champion trained 94 teachers from 57 schools districtwide. Cafeteria servings
      overall and fruit and vegetable servings, the primary outcomes, did not increase
      in SNaX schools versus matched-comparison schools. Our mixed-methods evaluation
      of SNaX showed acceptability and fidelity, but not effectiveness. Effectiveness
      may be improved by providing technical assistance to community stakeholders on
      how to tailor core intervention components while maintaining fidelity.

PMID- 29444326
TI  - Data maturity and follow-up in time-to-event analyses.
AB  - We propose methods to determine the minimum number of subjects remaining at risk
      after which Kaplan-Meier survival plots for time-to-event outcomes should be
      curtailed, as, once the number remaining at risk drops below this minimum, the
      survival estimates are no longer meaningful in the context of the investigation.
      The size of the decrease of the Kaplan-Meier survival estimate S(t) at time t if
      one extra event should occur is considered in two ways. In the first approach,
      the investigator sets a maximum acceptable absolute decrease in S(t) should one
      extra event occur. In the second, a minimum acceptable number of subjects still
      at risk is calculated by comparing the size of the decrease in S(t) if an extra
      event should occur with the variability of the survival estimate had all subjects
      been followed to that time (confidence interval approach). We recommend
      calculating both limits for the number still at risk and then making an informed
      choice in the context of the particular investigation. We explore further how the
      amount of information actually available can assist in considering issues of data
      maturity for studies whose outcome of interest is a survival percentage at a
      particular time point. We illustrate the approaches with a number of published
      studies having differing sample sizes and censoring issues. In particular, one
      study was the subject of some controversy regarding how far in time the Kaplan
      Meier plot should be extended. The proposed methods allow for limits to be
      calculated simply using the output provided by most statistical packages.

PMID- 29444327
TI  - Structural and Functional Analysis of UGT92G6 Suggests an Evolutionary Link
      Between Mono- and Disaccharide Glycoside-Forming Transferases.
AB  - Glycosylation mediated by UDP-dependent glycosyltransferase (UGT) is one of the
      most common reactions for the biosynthesis of small molecule glycosides. As
      glycosides have various biological roles, we characterized UGT genes from
      grapevine (Vitis vinifera). In silico analysis of VvUGT genes that were highly
      expressed in leaves identified UGT92G6 which showed sequence similarity to both
      monosaccharide and disaccharide glucoside-forming transferases. The recombinant
      UGT92G6 glucosylated phenolics, among them caffeic acid, carvacrol, eugenol and
      raspberry ketone, and also accepted geranyl glucoside and citronellyl glucoside.
      Thus, UGT92G6 formed mono- and diglucosides in vitro from distinct compounds. The
      enzyme specificity constant Vmax/Km ratios indicated that UGT92G6 exhibited the
      highest specificity towards caffeic acid, producing almost equal amounts of the 3
      and 4-O-glucoside. Transient overexpression of UGT92G6 in Nicotiana benthamiana
      leaves confirmed the production of caffeoyl glucoside; however, the level of
      geranyl diglucoside was not elevated upon overexpression of UGT92G6, even after
      co-expression of genes encoding geraniol synthase and geraniol UGT to provide
      sufficient precursor. Comparative sequence and 3-D structure analysis identified
      a sequence motif characteristic for monoglucoside-forming UGTs in UGT92G6,
      suggesting an evolutionary link between mono- and disaccharide glycoside UGTs.
      Thus, UGT92G6 functions as a mono- and diglucosyltransferase in vitro, but acts
      as a caffeoyl glucoside UGT in N. benthamiana.

PMID- 29444328
TI  - Influence of Anatomic Changes on the Outcomes of Carotid Siphon Aneurysms After
      Deployment of Flow-Diverter Stents.
AB  - BACKGROUND: Flow-diverter stent (FDS) deployment can cause morphological and
      hemodynamic changes in the carotid siphon (CS), influencing the occlusion rate of
      aneurysms in this location. OBJECTIVE: To evaluate morphological changes to the
      CS after FDS deployment and their relationship with the rate of occlusion of
      intracranial aneurysms. METHODS: A cohort of 183 patients with CS aneurysms were
      treated by deployment of Pipeline(r) FDS (Medtronic Inc, Dublin, Ireland). Their
      CSs were classified as type U, V, C, or S, depending on morphology. The posterior
      and anterior bend angles were measured on strict lateral cerebral angiogram with
      digital subtraction before FDS deployment, immediately after deployment, and at 6
      mo. Differences between angles were analyzed to identify any correlations with
      rates of aneurysm occlusion, using the O'Kelly-Marotta classification. RESULTS:
      FDS deployment was associated with immediate changes in CS morphology. The mean
      anterior angle increased from 3.97 +/- 25.06 degrees  to 22.05 +/- 25.18 degrees 
      (P  < .001) and the mean posterior angle increased from 71.98 +/- 31.27 degrees 
      to 79.43 +/- 31.80 degrees  (P  <  .001). Multivariate analysis revealed a
      progressive, statistically significant increase in frequency of complete (grade
      D) occlusion at 6-mo follow-up with increasing anterior bend angle (prevalence
      ratios (PR) = 1.42 for increases between 5.3 degrees  and 12 degrees , P  = 
      .017; PR = 1.56 for increases between 12.1 degrees  and 27.6 degrees , P  = 
      .002; PR = 1.83 for increases >27.6 degrees , P  <  .001, all vs increases <5.3
      degrees ). CONCLUSION: FDS deployment induces changes in CS morphology.
      Specifically, increases in mean anterior angle are associated with better
      radiological results on 6-mo follow-up digital subtraction angiography.

PMID- 29444329
TI  - Gastroesophageal reflux symptoms are not sufficient to guide esophageal function
      testing in lung transplant candidates.
AB  - Gastroesophageal reflux disease and esophageal dysmotility are prevalent in
      patients with advanced lung disease and are associated with graft dysfunction
      following lung transplantation. As a result, many transplant centers perform
      esophageal function testing as part of the wait-listing process but guidelines
      for testing in this population are lacking. The aim of this study is to describe
      whether symptoms of gastroesophageal reflux correlate with abnormal results on pH
      metry and high-resolution manometry and can be used to identify those who require
      testing. We performed a retrospective cohort study of 226 lung transplant
      candidates referred for high-resolution manometry and pH-metry over a 12-month
      period in 2015. Demographic data, results of a standard symptom questionnaire and
      details of esophageal function testing were obtained. Associations between the
      presence of symptoms and test results were analyzed using Fisher's exact tests
      and multivariable logistic regression. The most common lung disease diagnosis was
      interstitial lung disease (N = 131, 58%). Abnormal pH-metry was seen in 116 (51%)
      patients and the presence of symptoms was significantly associated with an
      abnormal study (p < 0.01). Dysmotility was found in 98 (43%) patients, with major
      peristaltic or esophageal outflow disorders in 45 (20%) patients. Symptoms were
      not correlated with findings on esophageal high-resolution manometry. Fifteen of
      25 (60%) asymptomatic patients had an abnormal manometry or pH-metry. These
      results demonstrate that in patients with advanced lung disease, symptoms of
      gastroesophageal reflux increase the likelihood of elevated acid exposure on pH
      metry but were not associated with dysmotility. Given the proportion of
      asymptomatic patients with abnormal studies and associated post-transplant risks,
      a practice of universal high-resolution manometry and pH-metry testing in this
      population is justifiable.

PMID- 29444330
TI  - Increased species-assignment of filamentous fungi using MALDI-TOF MS coupled with
      a simplified sample processing and an in-house library.
AB  - In this study we evaluated the capacity of MALDI-TOF MS (Bruker Daltonics,
      Bremen, Germany) to identify clinical mould isolates. We focused on two aspects
      of MALDI-TOF MS identification: the sample processing and the database. Direct
      smearing of the sample was compared with a simplified processing consisting of
      mechanical lysis of the moulds followed by a protein extraction step. Both
      methods were applied to all isolates and the Filamentous Fungi Library 1.0
      (Bruker Daltonics) was used for their identification. This approach allowed the
      correct species-level identification of 25/34 Fusarium spp. and 10/10 Mucor
      circinelloides isolates using the simplified sample processing. In addition, 7/34
      Fusarium spp. and 1/21 Pseudallescheria/Scedosporium spp. isolates were correctly
      identified at the genus level. The remaining isolates-60-could not be identified
      using the commercial database, mainly because of the low number of references for
      some species and the absence of others. Thus, an in-house library was built with
      63 local isolates previously characterized using DNA sequence analysis. Its
      implementation allowed the accurate identification at the species level of 94
      isolates (91.3%) and the remaining nine isolates (8.7%) were correctly identified
      at the genus level. No misidentifications at genus level were detected. In
      conclusion, with improvements of both the sample preparation and the feeding of
      the database, MALDI-TOF MS is a reliable, ready to use method to identify moulds
      of clinical origin in an accurate, rapid, and cost-effective manner.

PMID- 29444331
TI  - Validation of the ACR-EULAR criteria for primary Sjogren's syndrome in a Dutch
      prospective diagnostic cohort.
AB  - Objectives: To validate the ACR-EULAR classification criteria for primary SS
      (pSS), and compare them to the American-European Consensus Group (AECG) and ACR
      criteria in a Dutch prospective diagnostic cohort. Methods: Consecutive patients
      (n = 129) referred for suspicion of pSS underwent a multidisciplinary evaluation,
      including a labial and/or parotid gland biopsy. Patients with an incomplete work
      up (n = 8) or associated systemic auto-immune disease (n = 7) were excluded. The
      ACR-EULAR classification was compared with expert classification, AECG and ACR
      classification. Additionally, the accuracy of individual ACR-EULAR items in
      discriminating pSS from non-pSS was evaluated. The validity of criteria sets was
      described separately using parotid or labial gland biopsy results for
      classification. Results: Of the 114 evaluated patients, the expert panel
      classified 34 (30%) as pSS and 80 (70%) as non-pSS. Using labial gland biopsy
      results, ACR-EULAR classification showed 87% absolute agreement (kappa = 0.73)
      with expert classification, with a sensitivity of 97% and specificity of 83%.
      Using the parotid gland biopsy results, the ACR-EULAR criteria performed
      excellently as well. Focus score, anti-SSA titre and ocular staining score showed
      good to excellent accuracy, whereas unstimulated whole saliva and Schirmer's test
      had poor accuracy. The ACR-EULAR and AECG criteria had equal validity. Compared
      with ACR classification, ACR-EULAR classification showed higher sensitivity but
      lower specificity. Conclusion: The ACR-EULAR criteria showed good agreement with
      expert classification, but some patients may be misclassified as pSS.
      Unstimulated whole saliva and Schirmer's test showed poor discriminative value.
      The ACR-EULAR criteria performed equally to the AECG criteria, and had higher
      sensitivity but lower specificity than the ACR criteria.

PMID- 29444332
TI  - Are Eating Disorders and Related Symptoms Risk Factors for Suicidal Thoughts and
      Behaviors? A Meta-analysis.
AB  - This meta-analysis addressed whether eating disorders (EDs) are risk factors
      (i.e., longitudinal predictors) for suicidal thoughts and behaviors. We
      identified 2,611 longitudinal studies published through August 1, 2017. Inclusion
      required studies include at least one longitudinal analysis predicting suicide
      ideation, attempt, or death using an ED diagnosis and/or symptom. Fourteen
      studies (42 prediction cases) met criteria. Results indicated that clinically
      diagnosed EDs and disordered eating symptoms were significant but weak predictors
      of suicide attempts but not death. Effects remained weak when moderators were
      considered. By reviewing the methodological limitations of previous research,
      these results highlight avenues for future research.

PMID- 29444333
TI  - Morale in nursing students: A priority for nurse retention.

PMID- 29444334
TI  - Optimized methods of chromatin immunoprecipitation for profiling histone
      modifications in industrial microalgae Nannochloropsis spp.
AB  - Epigenetic factors such as histone modifications play integral roles in plant
      development and stress response, yet their implications in algae remain poorly
      understood. In the industrial oleaginous microalgae Nannochloropsis spp., the
      lack of an efficient methodology for chromatin immunoprecipitation (ChIP), which
      determines the specific genomic location of various histone modifications, has
      hindered probing the epigenetic basis of their photosynthetic carbon conversion
      and storage as oil. Here, a detailed ChIP protocol was developed for
      Nannochloropsis oceanica, which represents a reliable approach for the analysis
      of histone modifications, chromatin state, and transcription factor-binding sites
      at the epigenetic level. Using ChIP-qPCR, genes related to photosynthetic carbon
      fixation in this microalga were systematically assessed. Furthermore, a ChIP-Seq
      protocol was established and optimized, which generated a genome-wide profile of
      histone modification events, using histone mark H3K9Ac as an example. These
      results are the first step for appreciation of the chromatin landscape in
      industrial oleaginous microalgae and for epigenetics-based microalgal feedstock
      development.

PMID- 29444336
TI  - Clinician surveys: time to make better use of this valuable resource for
      dermatologists.

PMID- 29444335
TI  - Effectiveness of mobile cooperation intervention on students' clinical learning
      outcomes: A randomized controlled trial.
AB  - AIMS: The aim of this study was to evaluate the effectiveness of the mobile
      cooperation intervention in improving the competence and self-efficacy of
      students and the quality of the clinical learning environment. BACKGROUND: For
      students, the clinical practicum is challenging as such and moreover the student 
      teacher cooperation, which supports the clinical learning of the students, has
      become complicated. Mobile applications have potential but their role in
      facilitating this cooperation remains unknown. DESIGN: A parallel-group
      randomized controlled trial. METHODS: Data were collected between January-March
      2015 in Finland. The nursing students were randomly allocated to an intervention
      group (N = 52) or control group (N = 50). The intervention group used a mobile
      application to cooperate with the teacher during the clinical practicum. The
      control group engaged in standard cooperation. The primary outcome was
      competence. The secondary outcomes comprised self-efficacy and the quality of the
      clinical learning environment. Nurse Competence Scale, Self-efficacy in Clinical
      Performance instrument and the Clinical Learning Environment, Supervision and
      Nurse Teacher scale were used for student self-assessments. For the main
      analysis, hierarchical linear mixed models were used with the intention-to-treat
      principle. RESULTS: Competence and self-efficacy showed no significant between
      group differences in mean improvements, but significant improvements in both
      groups were detected over the 5 weeks. Satisfaction with the clinical learning
      environment showed no significant between-group differences, however, the role of
      the nurse teacher subscale, especially regarding cooperation, showed significant
      group differences. CONCLUSION: The mobile cooperation intervention was not
      significantly effective in improving individual outcomes, but did seem to improve
      significantly some aspects of the contextual outcomes. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov: NCT02635295.

PMID- 29444337
TI  - Social network analysis: Presenting an underused method for nursing research.
AB  - AIM: This paper introduces social network analysis as a versatile method with
      many applications in nursing research. BACKGROUND: Social networks have been
      studied for years in many social science fields. The methods continue to advance
      but remain unknown to most nursing scholars. DESIGN: Discussion paper. DATA
      SOURCES: English language and interpreted literature was searched from Ovid
      Healthstar, CINAHL, PubMed Central, Scopus and hard copy texts from 1965 - 2017.
      DISCUSSION: Social network analysis first emerged in nursing literature in 1995
      and appears minimally through present day. To convey the versatility and
      applicability of social network analysis in nursing, hypothetical scenarios are
      presented. The scenarios are illustrative of three approaches to social network
      analysis and include key elements of social network research design. IMPLICATIONS
      FOR NURSING: The methods of social network analysis are underused in nursing
      research, primarily because they are unknown to most scholars. However, there is
      methodological flexibility and epistemological versatility capable of supporting
      quantitative and qualitative research. The analytic techniques of social network
      analysis can add new insight into many areas of nursing inquiry, especially those
      influenced by cultural norms. Furthermore, visualization techniques associated
      with social network analysis can be used to generate new hypotheses. CONCLUSION:
      Social network analysis can potentially uncover findings not accessible through
      methods commonly used in nursing research. Social networks can be analysed based
      on individual-level attributes, whole networks and subgroups within networks.
      Computations derived from social network analysis may stand alone to answer a
      research question or incorporated as variables into robust statistical models.

PMID- 29444338
TI  - Construct validity of the Heart Failure Screening Tool (Heart-FaST) to identify
      heart failure patients at risk of poor self-care: Rasch analysis.
AB  - AIM: The aim of this study was to psychometrically evaluate the Heart Failure
      Screening Tool (Heart-FaST) via: (1) examination of internal construct validity;
      (2) testing of scale function in accordance with design; and (3) recommendation
      for change/s, if items are not well adjusted, to improve psychometric credential.
      BACKGROUND: Self-care is vital to the management of heart failure. The Heart-FaST
      may provide a prospective assessment of risk, regarding the likelihood that
      patients with heart failure will engage in self-care. DESIGN: Psychometric
      validation of the Heart-FaST using Rasch analysis. METHOD: The Heart-FaST was
      administered to 135 patients (median age = 68, IQR = 59-78 years; 105 males)
      enrolled in a multidisciplinary heart failure management program. The Heart-FaST
      is a nurse-administered tool for screening patients with HF at risk of poor self
      care. A Rasch analysis of responses was conducted which tested data against Rasch
      model expectations, including whether items serve as unbiased, non-redundant
      indicators of risk and measure a single construct and that rating scales operate
      as intended. RESULTS: The results showed that data met Rasch model expectations
      after rescoring or deleting items due to poor discrimination, disordered
      thresholds, differential item functioning, or response dependence. There was no
      evidence of multidimensionality which supports the use of total scores from Heart
      FaST as indicators of risk. CONCLUSION: Aggregate scores from this modified
      screening tool rank heart failure patients according to their "risk of poor self
      care" demonstrating that the Heart-FaST items constitute a meaningful scale to
      identify heart failure patients at risk of poor engagement in heart failure self
      care.

PMID- 29444339
TI  - Nursing Intensive-Care Satisfaction Scale [NICSS]: Development and validation of
      a patient-centred instrument.
AB  - AIM: The aim of this study was to develop and validate the Nursing Intensive-Care
      Satisfaction Scale to measures satisfaction with nursing care from the critical
      care patient's perspective. BACKGROUND: Instruments that measure satisfaction
      with nursing cares have been designed and validated without taking the patient's
      perspective into consideration. Despite the benefits and advances in measuring
      satisfaction with nursing care, none instrument is specifically designed to
      assess satisfaction in intensive care units. DESIGN: Instrument development.
      METHODS: The population were all discharged patients (January 2013 - January
      2015) from three Intensive Care Units of a third level hospital (N = 200). All
      assessment instruments were given to discharged patients and 48 hours later, to
      analyse the temporal stability, only the questionnaire was given again. The
      validation process of the scale included the analysis of internal consistency,
      temporal stability; validity of construct through a confirmatory factor analysis;
      and criterion validity. RESULTS: Reliability was 0.95. The intraclass correlation
      coefficient for the total scale was 0.83 indicating a good temporal stability.
      Construct validity showed an acceptable fit and factorial structure with four
      factors, in accordance with the theoretical model, being Consequences factor the
      best correlated with other factors. Criterion validity, presented a correlation
      between low and high (range: 0.42-0.68). CONCLUSIONS: The scale has been designed
      and validated incorporating the perspective of critical care patients. Thanks to
      its reliability and validity, this questionnaire can be used both in research and
      in clinical practice. The scale offers a possibility to assess and develop
      interventions to improve patient satisfaction with nursing care.

PMID- 29444340
TI  - Antipsychotics, Delirium, and Acute Respiratory Distress Syndrome: What Is the
      Link?
AB  - Acute respiratory distress syndrome (ARDS) is an acute inflammatory process that
      impairs the ability of the lungs to oxygenate and ultimately leads to respiratory
      failure. Patients who develop ARDS often have prolonged and complicated hospital
      courses putting them at risk for intensive care unit (ICU) delirium. Patients
      with ICU delirium often need chemical sedation, mechanical ventilation, prolonged
      duration of ICU and hospital stays, and they experience long-term cognitive
      impairment and increased mortality. In a patient with ARDS, ICU delirium further
      complicates the hospital course and increases the risk of morbidity and
      mortality. Antipsychotics are prescribed to decrease the severity and duration of
      ICU delirium, thus potentially decreasing their risk of morbidity and mortality.
      However, antipsychotics are associated with many adverse effects including
      respiratory failure. Given the long-term sequelae associated with the development
      of ICU delirium and the risks associated with antipsychotic use, clinicians must
      weigh the risks and benefits of antipsychotic use. This review investigates the
      interrelationship between ARDS, delirium, and antipsychotic use. In addition to
      discussing relevant studies evaluating antipsychotics for the prevention and
      treatment of delirium, we investigate safety concerns with the use of
      antipsychotics, especially as they relate to ARDS. Using the data compiled in
      this review, clinicians can make an informed decision about the use of
      antipsychotics for the prevention or treatment of delirium, with special
      consideration for their patients with ARDS. Future studies are needed to
      critically evaluate antipsychotic timing, dose, and duration for the prevention
      and treatment of ICU delirium and specifically evaluate the impact in special
      populations, particularly patients with ARDS.

PMID- 29444341
TI  - High-Fat Diet-Induced Obesity Promotes Expansion of Bone Marrow Adipose Tissue
      and Impairs Skeletal Stem Cell Functions in Mice.
AB  - Obesity represents a risk factor for development of insulin resistance and type 2
      diabetes. In addition, it has been associated with increased adipocyte formation
      in the bone marrow (BM) along with increased risk for bone fragility fractures.
      However, little is known on the cellular mechanisms that link obesity, BM
      adiposity, and bone fragility. Thus, in an obesity intervention study in C57BL/6J
      mice fed with a high-fat diet (HFD) for 12 weeks, we investigated the molecular
      and cellular phenotype of bone marrow adipose tissue (BMAT), BM progenitor cells,
      and BM microenvironment in comparison to peripheral adipose tissue (AT). HFD
      decreased trabecular bone mass by 29%, cortical thickness by 5%, and increased BM
      adiposity by 184%. In contrast to peripheral AT, BMAT did not exhibit pro
      inflammatory phenotype. BM progenitor cells isolated from HFD mice exhibited
      decreased mRNA levels of inflammatory genes (Tnfalpha, IL1beta, Lcn2) and did not
      manifest an insulin resistant phenotype evidenced by normal levels of pAKT after
      insulin stimulation as well as normal levels of insulin signaling genes. In
      addition, BM progenitor cells manifested enhanced adipocyte differentiation in
      HFD condition. Thus, our data demonstrate that BMAT expansion in response to HFD
      exerts a deleterious effect on the skeleton. Continuous recruitment of progenitor
      cells to adipogenesis leads to progenitor cell exhaustion, decreased recruitment
      to osteoblastic cells, and decreased bone formation. In addition, the absence of
      insulin resistance and inflammation in the BM suggest that BMAT buffers extra
      energy in the form of triglycerides and thus plays a role in whole-body energy
      homeostasis. (c) 2018 The Authors. Journal of Bone and Mineral Research Published
      by Wiley Periodicals, Inc.

PMID- 29444342
TI  - The five-factor model of personality, work stress and professional quality of
      life in neonatal intensive care unit nurses.
AB  - AIMS: The study aim was to determine the direct and indirect relations of the
      five-factor model of personality traits and work stress with professional quality
      of life in neonatal nurses. BACKGROUND: Neonatal intensive care nursing has
      positive and negative effects on neonatal nurses' psychological well-being.
      Although individual and situational factors interact to influence professional
      quality of life, there have been few studies of these relationships in neonatal
      nurses. DESIGN: A cross-sectional study conducted in 2016. METHODS: Self-report
      questionnaires were used to measure professional quality of life (burnout,
      secondary traumatic stress and compassion satisfaction), five-factor model of
      personality traits (neuroticism, agreeableness, extraversion, conscientiousness
      and openness) and work stress (role ambiguity, role conflict and role overload).
      RESULTS: One hundred and forty (34%) of 405 eligible neonatal nurses provided the
      data. After controlling for work stress, neuroticism and agreeableness were
      related to burnout, neuroticism was related to secondary traumatic stress, and
      extraversion was related to compassion satisfaction. Work stress controlled for
      personality traits was related to burnout and secondary traumatic stress, but not
      to compassion satisfaction. Neuroticism moderated the effect of work stress on
      secondary traumatic stress and agreeableness and openness moderated the effect of
      work stress on compassion satisfaction. Work stress mediated the effect of
      neuroticism and extraversion on burnout and the effects of extraversion and
      conscientiousness on compassion satisfaction. CONCLUSION: Strategies to reduce
      work stress may not lessen burnout and secondary traumatic stress or increase
      compassion satisfaction in neonatal nurses who are prone to high neuroticism, low
      agreeableness and low extraversion.

PMID- 29444343
TI  - Shift from IgE-mediated cow's milk allergy to food protein-induced enterocolitis
      syndrome in 2 infants.

PMID- 29444344
TI  - Serum sickness-like reaction in a pediatric patient using omalizumab for chronic
      spontaneous urticaria.

PMID- 29444345
TI  - Completed Suicide Among Methamphetamine Users: A National Study.
AB  - All Australian cases of methamphetamine-related suicide (2009-2015) retrieved
      from the National Coronial Information System were examined to determine crude
      mortality rates, characteristics and circumstances of death, and blood
      toxicology. There were 300 cases, 18.2% of all methamphetamine-related deaths,
      and 1.6% of all completed suicides. The mean age was 33.1 years, and 77.0% were
      male. The crude mortality rate was 1.9 per 106 , with males having a
      significantly higher rate than females (2.9 vs. 0.9 per 106 ). A quarter were
      known to have previous suicide attempts, and a history of psychosis was noted in
      12.3%. In 40.7% of cases, witnesses described the decedent as having been
      agitated and/or aggressive immediately prior to the incident. The vast majority
      (85.3%), and of both sexes (males 87.0%, females 79.7%), used violent methods.
      Hanging (70.3%) was overwhelmingly the most frequent method among both males
      (70.1%) and females (71.0%). Prescription medications were frequently present:
      hypnosedatives (23.6%), antidepressants (19.5%), and antipsychotics (8.4%). Self
      poisoning cases were significantly more likely to have antidepressants (odds
      ratio: 4.2) and opioids (4.9) present, but less likely to have cannabis (0.3).
      Methamphetamine-related suicide makes a large contribution to methamphetamine
      related death and represents a substantial clinical and public health problem.

PMID- 29444346
TI  - Prenatal vitamin D status and respiratory and allergic outcomes in childhood: A
      meta-analysis of observational studies.
AB  - BACKGROUND: Prenatal vitamin D status may influence offspring's respiratory and
      allergic outcomes; however, evidence is inconclusive. A systematic review and
      meta-analysis were conducted on the association between 25-hydroxyvitamin D
      [25(OH)D] levels in maternal blood in pregnancy or cord blood at birth with the
      risk of offspring's respiratory and allergic conditions. METHODS: Two independent
      researchers conducted systematic searches for observational studies published
      until May 2017 using defined keywords on vitamin D and health outcomes, including
      respiratory tract infections (RTIs), wheeze, asthma, atopic eczema, allergic
      rhinitis, allergic sensitization, and lung function. Random-effects meta-analyses
      were conducted. RESULTS: A total of 34 from 547 retrieved articles were included.
      Increased prenatal exposure to 25(OH)D was inversely associated with risk of
      RTIs. Comparing the highest with the lowest category of 25(OH)D levels, the
      pooled odds ratio was 0.64 (95% CI 0.47, 0.87). A positive borderline association
      was found for lung function at school age (FEV1 z-score coefficient 0.07, 95% CI 
      0.01, 0.15). No associations were found for wheeze, asthma, atopic eczema,
      allergic rhinitis, and allergic sensitization. CONCLUSION: The introduction of
      public health measures to tackle vitamin D status in pregnancy may reduce the
      burden of RTIs in offspring. Current evidence does not support an impact on
      asthma and allergy.

PMID- 29444347
TI  - Inhibition of Escherichia coli O157:H7 on stainless steel using Pseudomonas
      veronii biofilms.
AB  - : We produced a Pseudomonas veronii biofilm on the surface of a stainless steel
      that is inhibitory to Escherichia coli O157:H7. Pseudomonas veronii strain KACC
      81051BP, isolated from lettuce, readily formed biofilm on the surface of
      stainless steel coupons (SSCs) immersed in tryptic soy broth at 25 degrees C.
      Cells showed significantly (P <= 0.05) enhanced tolerance to desiccation stress
      (43% relative humidity (RH)) and retained antimicrobial activity against E. coli
      O157:H7. The number of E. coli O157:H7 (control; 4.1 +/- 0.1 log CFU per coupon)
      on sterile SSCs decreased to 2.7 +/- 0.2 log CFU per coupon after exposure to 43%
      RH at 25 degrees C for 48 h, while the population of E. coli O157:H7 (4.1 +/- 0.0
      log CFU per coupon) on SSCs containing P. veronii biofilm decreased to below the
      theoretical detection limit (1.5 log CFU per coupon) within 24 h. The
      antimicrobial biofilm produced on stainless steel may have application in
      preventing cross-contamination by E. coli O157:H7 on other abiotic surfaces in
      food-contact environments. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of
      Escherichia coli O157:H7 on environmental surfaces of food manufacturing,
      transportation and storage facilities is a significant food safety concern
      because it can result in cross-contamination of food products. In this study, we
      developed a Pseudomonas veronii biofilm on the surface of a stainless steel that
      inhibits the growth of E. coli O157:H7. Since P. veronii in biofilm resists
      desiccation, it provides persistent antimicrobial activity. Information presented
      here provides novel and practical insights to developing biological strategies to
      inactivate E. coli O157:H7 on diverse surfaces in food processing and handling
      environments.

PMID- 29444348
TI  - Cerebrospinal fluid abacavir concentrations in HIV-positive patients following
      once-daily administration.
AB  - Abacavir is a widely used nucleotide reverse transcriptase inhibitor, for which
      cerebrospinal fluid (CSF) exposure has been previously assessed in twice-daily
      recipients. We studied abacavir CSF concentrations in 61 and nine HIV-positive
      patients taking abacavir once daily and twice daily, respectively. Patients on
      once-daily abacavir had higher plasma and CSF concentrations (96 vs. 22 ng ml-1 ,
      P = 0.038 and 123 vs. 49 ng ml-1 , P = 0.038) but similar CSF-to-plasma ratios
      (0.8 vs. 0.5, P = 0.500). CSF abacavir concentrations were adequate in patients
      receiving once-daily treatment.

PMID- 29444349
TI  - Suicidal Ideation in First-Episode Psychosis (FEP): Examination of Symptoms of
      Depression and Psychosis Among Individuals in an Early Phase of Treatment.
AB  - First-episode psychosis (FEP) is a particularly high-risk period for suicide, in
      which risk elevates by 60% within a first year of treatment as compared to later
      stages of illness. To date, much of the literature has focused on individuals
      with a longer duration of psychosis; thus, there is an urgency for research to
      examine suicide risk among individuals in FEP in the beginning stage of
      treatment. This study aimed to identify the relationships between demographic
      characteristics, symptoms of depression, psychosis (particularly positive
      symptoms of psychosis), and suicidal ideation among individuals in FEP. Secondary
      data were obtained from National Institute of Mental Health's Early Treatment
      Program of the Recovery After an Initial Schizophrenia Episode project (N = 404).
      Consistent with prior research, participants who experienced suicidal ideation
      during the study period reported having a longer duration of untreated psychosis
      and greater symptoms of depression. Further, positive symptoms of psychosis,
      namely hallucinations and delusions, were found to increase the odds of
      experiencing suicidal ideation. Findings point toward the implication that
      depression and positive symptoms of psychosis relate to the experience of
      suicidal ideation among individuals with a FEP and should be evaluated for and
      treated in the early stages of treatment.

PMID- 29444350
TI  - Nurses' beliefs about nursing diagnosis: A study with cluster analysis.
AB  - AIMS: To identify clusters of nurses in relation to their beliefs about nursing
      diagnosis among two populations (Italian and Spanish); to investigate differences
      among clusters of nurses in each population considering the nurses' socio
      demographic data, attitudes towards nursing diagnosis, intentions to make nursing
      diagnosis and actual behaviours in making nursing diagnosis. BACKGROUND: Nurses'
      beliefs concerning nursing diagnosis can influence its use in practice but this
      is still unclear. DESIGN: A cross-sectional design. METHODS: A convenience sample
      of nurses in Italy and Spain was enrolled. Data were collected between 2014-2015
      using tools, that is, a socio-demographic questionnaire and behavioural,
      normative and control beliefs, attitudes, intentions and behaviours scales.
      RESULTS: The sample included 499 nurses (272 Italians & 227 Spanish). Of these,
      66.5% of the Italian and 90.7% of the Spanish sample were female. The mean age
      was 36.5 and 45.2 years old in the Italian and Spanish sample respectively. Six
      clusters of nurses were identified in Spain and four in Italy. Three clusters
      were similar among the two populations. Similar significant associations between
      age, years of work, attitudes towards nursing diagnosis, intentions to make
      nursing diagnosis and behaviours in making nursing diagnosis and cluster
      membership in each population were identified. CONCLUSION: Belief profiles
      identified unique subsets of nurses that have distinct characteristics.
      Categorizing nurses by belief patterns may help administrators and educators to
      tailor interventions aimed at improving nursing diagnosis use in practice.

PMID- 29444351
TI  - Subyearling Siberian Sturgeon Acipenser baeri Fed a Diet Supplemented with
      ImmunoGen: Effects on Growth Performance, Body Composition, and Hematological and
      Serum Biochemical Parameters.
AB  - In this research, the effect of ImmunoGen (IMNO) on the growth indices,
      hematological parameters, and carcass composition of Siberian Sturgeon Acipenser
      baeri was investigated. After acclimation, fish (274.8 +/- 16.2 g) were allocated
      into 12 tanks (10 fish per tank) and triplicate groups were fed a control diet
      (0%) or diets containing 0.5, 1.0, or 1.5% IMNO for 75 d. At the end of the
      experiment, final length, final weight, and weight gain were significantly higher
      in the fish fed the diet containing 1.0% IMNO, though no significant differences
      were observed between the control and experimental diets containing 0.5% and 1.5%
      IMNO. In addition, there were no significant differences among diets in terms of
      hematological parameters and carcass composition. However, dietary IMNO
      significantly affected the serum biochemical parameters of Siberian Sturgeon,
      such as cholesterol, triglycerides, and IgM, with the highest level of IgM
      occurring in the 1.0% IMNO treatment and the lowest levels of cholesterol and
      triglycerides in the 1.5% IMNO treatment. The findings of this study thus
      indicate that the administration of 1.0% IMNO in diet positively affects the
      growth factors and some serum biochemical parameters of Siberian Sturgeon.

PMID- 29444352
TI  - Predictive performance of a genetic risk score using 11 susceptibility alleles
      for the incidence of Type 2 diabetes in a general Japanese population: a nested
      case-control study.
AB  - AIMS: To assess the predictive ability of a genetic risk score for the incidence
      of Type 2 diabetes in a general Japanese population. METHODS: This prospective
      case-control study, nested within a Japan Public Health Centre-based prospective
      study, included 466 participants with incident Type 2 diabetes over a 5-year
      period (cases) and 1361 control participants, as well as 1463 participants with
      existing diabetes and 1463 control participants. Eleven susceptibility single
      nucleotide polymorphisms, identified through genome-wide association studies and
      replicated in Japanese populations, were analysed. RESULTS: Most single
      nucleotide polymorphism loci showed directionally consistent associations with
      diabetes. From the combined samples, one single nucleotide polymorphism
      (rs2206734 at CDKAL1) reached a genome-wide significance level (odds ratio 1.28,
      95% CI 1.18-1.40; P = 1.8 * 10-8 ). Three single nucleotide polymorphisms
      (rs2206734 in CDKAL1, rs2383208 in CDKN2A/B, and rs2237892 in KCNQ1) were
      nominally significantly associated with incident diabetes. Compared with the
      lowest quintile of the total number of risk alleles, the highest quintile had a
      higher odds of incident diabetes (odds ratio 2.34, 95% CI 1.59-3.46) after
      adjusting for conventional risk factors such as age, sex and BMI. The addition to
      the conventional risk factor-based model of a genetic risk score using the 11
      single nucleotide polymorphisms significantly improved predictive performance;
      the c-statistic increased by 0.021, net reclassification improved by 6.2%, and
      integrated discrimination improved by 0.003. CONCLUSIONS: Our prospective
      findings suggest that the addition of a genetic risk score may provide modest but
      significant incremental predictive performance beyond that of the conventional
      risk factor-based model without biochemical markers.

PMID- 29444354
TI  - Clothing as a transport vector for airborne particles: Chamber study.
AB  - Strong evidence suggests that clothing serves as a reservoir of chemical
      pollutants and particles, including bioaerosols, which may have health
      significance. However, little is known about the role that clothing may play as a
      transport vector for inhaled airborne particles. Here, we contribute toward
      bridging the knowledge gap by conducting experiments to investigate clothing
      release fraction (CRF), determined as the size-dependent ratio of released to
      deposited particulate matter in the diameter range 0.5-10 MUm. In a fully
      controlled chamber with low background particle levels, we deployed a
      programmable robot to reproducibly quantify the size-dependent CRF as a function
      of motion type and intensity, dust loadings, and activity duration. On average,
      0.3%-3% of deposited particles were subsequently released with fabric motion,
      confirming that clothing can act as a vehicle for transporting airborne
      particles. The CRF increased with the vigor of movement and with dust loading.
      Rubbing and shaking the fabric were more effective than fabric stretching in
      resuspending particles. We also found that most of the release happened quickly
      after the onset of the resuspension activity. Particle size substantially
      influenced the CRF, with larger particles exhibiting higher values.

PMID- 29444353
TI  - Healthcare resource utilisation associated with skeletal-related events in
      European patients with multiple myeloma: Results from a prospective,
      multinational, observational study.
AB  - OBJECTIVES: Patients with multiple myeloma (MM) often experience debilitating
      skeletal-related events (SREs: pathologic fracture, radiation to bone [RB],
      surgery to bone [SB] or spinal cord compression [SCC]). This is the first
      comprehensive, prospective, observational analysis of healthcare resource
      utilisation (HRU), independently attributed to SREs by investigators, in patients
      with MM. METHODS: Eligible patients had lytic bone lesions, life expectancy >=6
      months, Eastern Cooperative Oncology Group performance status <=2 and >=1 SRE in
      the 97 days before enrolment. Data were collected retrospectively for 97 days
      before enrolment and prospectively for 18-21 months. RESULTS: Altogether, 153
      patients were enrolled from Germany, Italy, Spain and the United Kingdom. Of the
      281 observed SREs, 36.7% required inpatient stays (mean duration: 20.6 days per
      SRE [standard deviation (SD): 22.9]). SB and SCC were the SREs most likely to
      require stays (72.3% and 50.0% of SREs, respectively); SCC required the longest
      mean (SD) stay per event (40.5 [40.8] days). Overall, 179 SREs required
      outpatient visits; this was most likely for RB (74.8%) and least likely for non
      vertebral fracture (50.0%). CONCLUSIONS: All SREs were associated with
      substantial HRU; therefore, preventing SREs in MM will reduce the economic and
      resource burden on healthcare systems.

PMID- 29444355
TI  - Ethnic Variations of Trajectories in Suicide Ideation and Attempt: From Middle
      School to High School.
AB  - The purpose of this study was to compare patterns of suicide ideation and suicide
      attempt in three ethnic groups. We analyzed data from 463 students with ethnic
      backgrounds of African American (AA), Asian American (ASA), and European American
      (EA) for 6 years. The best fit model was a three-trajectory class model for all
      groups. The majority of adolescents belonged in the nonideators trajectory. The
      high level of ideation was found in the high ideators (4%), high-fluctuating
      ideators (8%), and high-decreasing ideators (4%) trajectory in AA, ASA, and EA,
      respectively. In the AA group, being a member of ideators was not a significant
      predictor of suicide attempt. In the ASA group, being a member of high
      fluctuating ideators was a significant predictor. In the EA group, being a member
      of both ideators predicted suicide attempt. The timing of onset, patterns of
      change, and peak time in the ideators trajectories in the three ethnic groups
      were markedly different. The high level of attempts found in the ASA-AA group was
      not explained by having suicide ideation. Findings suggest the need for in-depth
      examination of suicide behaviors across ethnic groups and culturally adapted
      preventive efforts with distinct developmental timing for adolescents from
      different ethnic backgrounds.

PMID- 29444356
TI  - Long-chain polyunsaturated fatty acids decline rapidly in milk from mothers
      delivering extremely preterm indicating the need for supplementation.
AB  - AIM: Our aim was to perform an in-depth analysis of the composition of fatty
      acids in milk from mothers delivering extremely preterm babies. We investigated
      longitudinal changes in milk fatty acid profiles and the relationship between
      several types of fatty acids, including omega-3 and omega-6. METHODS: Milk
      samples were collected at three stages of lactation from 78 mothers who delivered
      at less than 28 weeks of pregnancy at the Sahlgrenska University Hospital,
      Gothenburg, Sweden, from April 2013 to September 2015. Fatty acid composition was
      analysed by gas chromatography-mass spectrometry. RESULTS: A reduction in long
      chain polyunsaturated fatty acids (LCPUFAs) was observed during the lactation
      period. The concentrations of arachidonic acid and docosahexaenoic acid declined
      from medians of 0.34 to 0.22 mol% and 0.29 to 0.15 mol%, respectively, between
      postnatal day 7 and a postmenstrual age of 40 weeks. Strong correlations were
      found between the intermediates of several classes of fatty acids, including
      omega-3, omega-6 and omega-9. CONCLUSION: A rapid reduction in LCPUFA content in
      the mother's milk during the lactation period emphasises the importance of fatty
      acid supplementation to infants born extremely preterm, at least during the
      period corresponding to the third trimester, when rapid development of the brain
      and adipose tissue requires high levels of LCPUFAs.

PMID- 29444357
TI  - Safety of direct oral anticoagulants vs warfarin in patients with chronic liver
      disease and atrial fibrillation.
AB  - BACKGROUND: A complication of chronic liver disease (CLD) is the abnormality of
      coagulation. In clinical practice, this increased risk of bleeding has not been
      identified as a protective factor against stroke or systemic embolism associated
      with atrial fibrillation (AF). The objective of this study was to assess the
      safety of direct oral anticoagulant (DOAC) agents vs warfarin in CLD patients
      with AF. METHODS: This was a retrospective cohort study of patients with CLD and
      AF initiated on oral anticoagulants. Rates of all-cause bleeding were compared
      between warfarin and DOAC agents. Secondary endpoints included rates of major
      bleeding and other risk factors for bleeding on anticoagulant therapy. RESULTS:
      The all-cause bleeding rates were similar between the groups, with 8.4% per year
      in the DOAC (n = 75) group and 8.8% in warfarin (n = 158) group (HR 0.9, 95% CI
      0.4-1.8). No significant difference was noted in the rate of major bleeding. In
      the multivariable model, higher MELD-XI score and previous bleed were risk
      factors associated with increased bleeding. CONCLUSION: No significant
      differences in bleeding rates were noted in patients treated with warfarin and
      DOAC agents. Further studies evaluating DOAC agents are needed to better
      understand the optimal anticoagulation strategy in setting of CLD.

PMID- 29444358
TI  - A Complex Role for Lipocalin 2 in Bone Metabolism: Global Ablation in Mice
      Induces Osteopenia Caused by an Altered Energy Metabolism.
AB  - Lipocalin 2 (Lcn2) is an adipokine that carries out a variety of functions in
      diverse organs. We investigated the bone phenotype and the energy metabolism of
      Lcn2 globally deleted mice (Lcn2-/- ) at different ages. Lcn2-/- mice were
      largely osteopenic, exhibiting lower trabecular bone volume, lesser trabecular
      number, and higher trabecular separation when compared to wild-type (WT) mice.
      Lcn2-/- mice showed a lower osteoblast number and surface over bone surface, and
      subsequently a significantly lower bone formation rate, while osteoclast
      variables were unremarkable. Surprisingly, we found no difference in alkaline
      phosphatase (ALP) activity or in nodule mineralization in Lcn2-/- calvaria
      osteoblast cultures, while less ALP-positive colonies were obtained from freshly
      isolated Lcn2-/- bone marrow stromal cells, suggesting a nonautonomous osteoblast
      response to Lcn2 ablation. Given that Lcn2-/- mice showed higher body weight and
      hyperphagia, we investigated whether their osteoblast impairment could be due to
      altered energy metabolism. Lcn2-/- mice showed lower fasted glycemia and
      hyperinsulinemia. Consistently, glucose tolerance was significantly higher in
      Lcn2-/- compared to WT mice, while insulin tolerance was similar. Lcn2-/- mice
      also exhibited polyuria, glycosuria, proteinuria, and renal cortex vacuolization,
      suggesting a kidney contribution to their phenotype. Interestingly, the
      expression of the glucose transporter protein type 1, that conveys glucose into
      the osteoblasts and is essential for osteogenesis, was significantly lower in the
      Lcn2-/- bone, possibly explaining the in vivo osteoblast impairment induced by
      the global Lcn2 ablation. Taken together, these results unveil an important role
      of Lcn2 in bone metabolism, highlighting a link with glucose metabolism that is
      more complex than expected from the current knowledge. (c) 2018 American Society
      for Bone and Mineral Research.

PMID- 29444359
TI  - Drug survival and postdrug survival of first-line immunosuppressive treatments
      for atopic dermatitis: comparison between methotrexate and cyclosporine.
AB  - INTRODUCTION: Cyclosporine and methotrexate are the two preferred first-line
      immunosuppressive treatments in atopic dermatitis. The aim of this study was to
      compare the treatment profiles of methotrexate and cyclosporine in daily practice
      as the first-line immunosuppressive treatment in atopic dermatitis, using two
      survival analyses, 'drug survival' (time on the drug) and 'postdrug survival'
      (time between two drugs). METHODS: Retrospective study including patients with
      moderate-to-severe atopic dermatitis treated with methotrexate or cyclosporine as
      the first-line immunosuppressive treatment. The reasons for discontinuation of
      treatment were collected as follows: controlled disease, treatment failure, side
      event pregnancy and non-compliance. 'Drug survival' and 'postdrug survival'
      analyses were performed using the Kaplan-Meier method and predictive factors were
      analysed using uni- and multivariate Cox regression analyses. RESULTS: Fifty-six
      patients, among whom 25 patients treated with cyclosporine and 31 with
      methotrexate (median age: 34 +/- 15 years), were included between 2007 and 2016.
      Reasons for discontinuation were not significantly different between 'controlled
      disease' and other reasons (P = 0.11). The median 'drug survival' was
      significantly longer for methotrexate (23 months) than for cyclosporine (8
      months) (P < 0.0001). Six months from baseline, 93% of patients treated with
      methotrexate were still being treated vs 63% among patients treated with
      cyclosporine. The median of 'postdrug survival' was significantly longer for
      methotrexate (12 months) than for cyclosporine (2 months). Only treatment with
      CYC was a predictive factor for decreased 'drug survival' and 'postdrug
      survival'. CONCLUSION: This is the first direct comparison between methotrexate
      and cyclosporine as first-line immunosuppressive treatments for moderate-to
      severe atopic dermatitis in daily practice. We evidenced two different treatment
      profiles: the duration of methotrexate administration is longer than that of
      cyclosporine. 'Postdrug survival' could be a new tool to assess the maintenance
      of effect of a drug after withdrawal in atopic dermatitis, and more broadly in
      chronic skin disease.

PMID- 29444360
TI  - Two EDA gene mutations in chinese patients with hypohidrotic ectodermal
      dysplasia.

PMID- 29444361
TI  - Environmental exposure to polycyclic aromatic hydrocarbons, kitchen ventilation,
      fractional exhaled nitric oxide, and risk of diabetes among Chinese females.
AB  - Diabetes is related to exposure to polycyclic aromatic hydrocarbons (PAHs),
      inflammation in the body, and housing characters. However, associations of
      urinary monohydroxy-PAHs (OH-PAHs) or fractional exhaled nitric oxide (FeNO) with
      diabetes risk in relation to housing characters are unclear. In this study, 2645
      individuals were drawn from the baseline survey of the Wuhan-Zhuhai Cohort Study.
      Associations of diabetes with urinary OH-PAHs or FeNO among cooking participants
      were estimated using logistic regression models. Among women with self-cooking
      meals, urinary OH-PAH levels were positively associated with diabetes risk (P <
      .05); the cooking women with high FeNO (>=25 ppb) had a 59% increase in the risk
      of diabetes (OR: 1.59, 95% CI: 1.06, 2.38), compared with those with low FeNO
      (<25 ppb). The cooking women with use of kitchen exhaust fans/hoods had a 52%
      decrease in the risk of diabetes (OR: 0.48, 95% CI: 0.27, 0.84), compared with
      those with nonuse of kitchen exhaust fans/hoods. The results indicated that the
      cooking women had an elevated risk of diabetes, which may be partly explained by
      an increase in the PAH body burden and higher inflammatory responses. Use of
      kitchen exhaust fan/hood can be associated with a lower risk of diabetes.

PMID- 29444362
TI  - The use of JAK inhibitors in the treatment of progressive systemic sclerosis.

PMID- 29444363
TI  - If it's red and scaly look for fungus: remember cutaneous protothecosis.

PMID- 29444364
TI  - A cross-sectional analysis of the effects of increased resident autonomy on
      practice patterns and patient satisfaction.

PMID- 29444365
TI  - A case of atypical eosinophilic pustular folliculitis that emerged following the
      administration of capecitabine.

PMID- 29444366
TI  - Is atopic dermatitis associated with obesity? A systematic review of
      observational studies.
AB  - Obesity has been associated with atopic dermatitis (AD); however, the results
      have been conflicting. Our aim was to provide an update on current knowledge from
      observational studies addressing the possible association between obesity and AD.
      Systematic literature review was performed by identifying studies addressing a
      possible link between AD and overweight/obesity from PubMed, EMBASE and the
      Cochrane Library in accordance with the Preferred Reporting Items for Systematic
      reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included
      studies was assessed using the Newcastle-Ottawa Scale. A total of 45 studies
      (comprising more than 90 000 individuals with AD) fulfilled the criteria and were
      included in the present review. The available studies revealed inconsistencies,
      but the majority indicated that obesity is associated with AD. Studies addressing
      obesity in infancy or early childhood (age < 2 years) and AD reported a positive
      association. From childhood into adulthood, there is a discrepancy in the
      observations, as the more recent prospective studies found a positive
      association, whereas this was not observed in older cross-sectional studies. The
      inconsistency might be explained by the difference in study design, the
      diagnostic criteria of AD, regional differences, and by the varied definitions of
      overweight and obesity used in the studies. In Conclusion, overweight/obesity is
      associated with an increased risk of AD. Large prospective cohort studies are
      required to confirm the association between AD and obesity and the possibility
      that weight control in childhood may help to mitigate or reverse AD symptoms.

PMID- 29444367
TI  - Numbers on injectable treatments in the Netherlands in 2016.

PMID- 29444369
TI  - Rotaviral nonstructural protein 4 triggers dynamin-related protein 1-dependent
      mitochondrial fragmentation during infection.
AB  - Dynamic equilibrium between mitochondrial fission and mitochondrial fusion serves
      as an important quality control system within cells ensuring cellular vitality
      and homeostasis. Viruses often target mitochondrial dynamics as a part of their
      obligatory cellular reprogramming. The present study was undertaken to assess the
      status and regulation of mitochondrial dynamics during rotavirus infection.
      Distinct fragmentation of mitochondrial syncytia was observed during late hours
      of RV (SA11, Wa, A5-13) infection. RV nonstructural protein 4 (NSP4) was
      identified as the viral trigger for disrupted mitochondrial morphology. Severance
      of mitochondrial interconnections was found to be a dynamin-related protein 1
      (Drp1)-dependent process resulting synergistically from augmented mitochondrial
      fission and attenuated mitochondrial fusion. Cyclin-dependent kinase 1 was
      subsequently identified as the cellular kinase responsible for fission-active
      Ser616 phosphorylation of Drp1. In addition to its positive role in mitochondrial
      fission, Drp1 also resulted in mitochondrial translocation of E3-ubiquitin ligase
      Parkin leading to degradation of mitochondrial fusion protein Mitofusin 1.
      Interestingly, RV-NSP4 was found to interact with and be involved in recruiting
      fission-active pool of Serine 616 phosphoDrp1 (Ser616 pDrp1) to mitochondria
      independent of accessory adaptors Mitochondrial fission factor and Fission
      protein 1 (Fis1). Inhibition of either Drp1 or Ser616 pDrp1 resulted in
      significant decrease in RV-NSP4-induced intrinsic apoptotic pathway. Overall,
      this study underscores an efficient strategy utilised by RV to couple apoptosis
      to mitochondrial fission facilitating dissemination of viral progeny.

PMID- 29444368
TI  - Establishment of an in vivo simulating co-culture assay platform for genotoxicity
      of multi-walled carbon nanotubes.
AB  - Engineered nanomaterials (ENM) are now used in a wide variety of fields, and,
      thus, their safety should urgently be assessed and secured. It has been suggested
      that inflammatory responses via the phagocytosis of ENM by macrophages is a key
      mechanism for their genotoxicity. The present study was conducted to establish a
      mechanism-based assay to evaluate the genotoxicity of ENM under conditions
      simulating an in vivo situation, featuring a co-culture system of murine lung
      resident cells (GDL1) and immune cells (RAW264.7). GDL1 were cultured with or
      without RAW264.7, exposed to a multi-walled carbon nanotube (MWCNT), and then
      analyzed for mutagenicity and underlying mechanisms. Mutation frequencies induced
      in GDL1 by the MWCNT were significantly greater with the co-existence of RAW264.7
      than in its absence. Mutation spectra observed in GDL1 co-cultured with RAW264.7
      were different from those seen in GDL1 cultured alone, but similar to those
      observed in the lungs of mice exposed to the MWCNT in vivo. Inflammatory
      cytokines, such as IL-1beta and TNF-alpha, were produced from RAW264.7 cells
      treated with the MWCNT. The generation of reactive oxygen species and the
      formation of 8-oxodeoxyguanosine in GDL1 exposed to the MWCNT were greater in the
      co-culture conditions than in the single culture conditions. Based on these
      findings, it is indicated that inflammatory responses are involved in the
      genotoxicity of MWCNT, and that the presently established, novel in vitro assay
      featuring a co-culture system of tissue resident cells with immune cells is
      suitable to evaluate the genotoxicity of ENM.

PMID- 29444371
TI  - Whole-exome sequencing for diagnosis of hereditary ichthyosis.
AB  - BACKGROUND: Hereditary ichthyosis constitutes a diverse group of cornification
      disorders. Identification of the molecular cause facilitates optimal patient
      care. OBJECTIVE: We wanted to estimate the diagnostic yield of applying whole
      exome sequencing (WES) in the routine genetic workup of inherited ichthyosis.
      METHODS: During a 3-year-period, all ichthyosis patients, except X-linked and
      mild vulgar ichthyosis, consecutively admitted to a university hospital clinic
      were offered WES with subsequent analysis of ichthyosis-related genes as a first
      line genetic investigation. Clinical and molecular data have been collected
      retrospectively. RESULTS: Genetic variants causative for the ichthyosis were
      identified in 27 of 34 investigated patients (79.4%). In all, 31 causative
      mutations across 13 genes were disclosed, including 12 novel variants. TGM1 was
      the most frequently mutated gene, accounting for 43.7% of patients suffering from
      autosomal recessive congenital ichthyosis (ARCI). CONCLUSION: Whole-exome
      sequencing appears an effective tool in disclosing the molecular cause of
      patients with hereditary ichthyosis seen in clinical practice and should be
      considered a first-tier genetic test in these patients.

PMID- 29444370
TI  - Cryptosporidium parvum disrupts intestinal epithelial barrier function via
      altering expression of key tight junction and adherens junction proteins.
AB  - Infection with the protozoan parasite Cryptosporidium parvum (CP) causes
      cryptosporidiosis, a widespread diarrhoeal disease. Impaired intestinal
      epithelial barrier function and increased permeability are most commonly
      associated with diarrhoeal diseases caused by enteric infections. However,
      studies on barrier disruption and underlying mechanisms in cryptosporidiosis are
      extremely limited. Epithelial tight junctions (TJs) and adherens junctions (AJs)
      are important in maintaining barrier integrity. Therefore, we examined the
      effects of CP infection on paracellular permeability and on the expression of the
      major TJ and AJ proteins utilising in vitro, ex vivo, and in vivo models. CP
      infection (0.5 * 106  oocysts/well in Transwell inserts, 24 hr) increased
      paracellular permeability (FITC-dextran flux) in Caco-2 cell monolayers and
      substantially decreased the protein levels of occludin, claudin 4, and E
      cadherin. Claudin 3, zonula occludens-1 (ZO1) and alpha-catenin were also
      significantly decreased, whereas claudins 1 and 2 and beta-catenin were not
      altered. Substantial downregulation of occludin, claudin 4, and E-cadherin was
      also observed in response to CP infection ex vivo in mouse enteroid-derived
      monolayers and in vivo in the ileal and jejunal mocosa of C57BL/6 mice. The mRNA
      levels of these proteins were also significantly decreased in CP-infected mouse
      ileum and jejunum but were unaltered in Caco-2 cells. Further, bafilomycin-A, an
      inhibitor of lysosomal proton pump, partially abrogated CP effects on occludin
      expression in Caco-2 cells, suggesting a potential role of posttranslational
      mechanisms, such as induction of protein degradation pathways, in mediating the
      effects of the parasite. Our studies suggest that disruption of barrier function
      via downregulation of specific key components of TJ and AJ could be a major
      mechanism underlying CP infection-induced diarrhoea.

PMID- 29444372
TI  - Primary cutaneous small/medium-sized pleomorphic T-cell lymphoproliferative
      disorder shows a common vascular pattern at dermoscopy.

PMID- 29444373
TI  - Changes in apoplastic peroxidase activity and cell wall composition are
      associated with cold-induced morpho-anatomical plasticity of wheat leaves.
AB  - Temperate grasses, such as wheat, become compact plants with small thick leaves
      after exposure to low temperature. These responses are associated with cold
      hardiness, but their underlying mechanisms remain largely unknown. Here we
      analyse the effects of low temperature on leaf morpho-anatomical structure, cell
      wall composition and activity of extracellular peroxidases, which play key roles
      in cell elongation and cell wall thickening, in two wheat cultivars with
      contrasting cold-hardening ability. A combined microscopy and biochemical
      approach was applied to study actively growing leaves of winter (ProINTA-Pincen)
      and spring (Buck-Patacon) wheat developed under constant warm (25  degrees C) or
      cool (5  degrees C) temperature. Cold-grown plants had shorter leaves but longer
      inter-stomatal epidermal cells than warm-grown plants. They had thicker walls in
      metaxylem vessels and mestome sheath cells, paralleled with accumulation of wall
      components, predominantly hemicellulose. These effects were more pronounced in
      the winter cultivar (Pincen). Cold also induced a sharp decrease in apoplastic
      peroxidase activity within the leaf elongating zone of Pincen, and a three-fold
      increase in the distal mature zone of the leaf. This was consistent with the
      enhanced cell length and thicker cell walls in this cultivar at 5  degrees C. The
      different response to low temperature of apoplastic peroxidase activity and
      hemicellulose between leaf zones and cultivar types suggests they might play a
      central role in the development of cold-induced compact morphology and cold
      hardening. New insights are presented on the potential temperature-driven role of
      peroxidases and hemicellulose in cell wall dynamics of grasses.

PMID- 29444374
TI  - International Medical Graduates in Abdominal Transplant Surgery Fellowships in
      the United States, response to letter by Schlottmann et al.

PMID- 29444375
TI  - The efficacy and safety of non-pharmacological therapies for the treatment of
      acne vulgaris: A systematic review and best-evidence synthesis.
AB  - BACKGROUND: Acne vulgaris is a multifaceted skin disorder, affecting more than
      85% of young individuals worldwide. Pharmacological therapy is not always
      desirable because of the development of antibiotic resistance or the potential
      risk of adverse effects. Non-pharmacological therapies can be viable alternatives
      for conventional therapies. However, sufficient evidence-based support in the
      efficacy and safety of non-pharmacological therapies is lacking. OBJECTIVE: To
      assess the efficacy and safety of several non-pharmacological therapies in the
      treatment of acne vulgaris. METHODS: A systematic literature review, including a
      best-evidence synthesis, was performed to identify literature. Three electronic
      databases were accessed and searched for studies published between January 2000
      and May 2017. RESULTS: Thirty-three eligible studies were included in our
      systematic review. Three main types of non-pharmacological therapies were
      identified laser- and light-based therapies, chemical peels and fractional
      microneedling radiofrequency. The majority of the included studies demonstrated a
      significant reduction in acne lesions. However, only seven studies had a high
      methodologic quality. Based on these seven trials, a best-evidence synthesis was
      conducted. Strong evidence was found for glycolic acid (10-40%). Moderate
      evidence was found for amino fruit acid (20-60%), intense pulsed light (400-700
      and 870-1200 nm) and the diode laser (1450 nm). Initially, conflicting evidence
      was found for pulsed dye laser (585-595 nm). The most frequently reported side
      effects for non-pharmacological therapies included erythema, tolerable pain,
      purpura, oedema and a few cases of hyperpigmentation, which were in most cases
      mild and transient. CONCLUSION: Circumstantial evidence was found for non
      pharmacological therapies in the treatment of acne vulgaris. However, the lack of
      high methodological quality among included studies prevented us to draw clear
      conclusions, regarding a stepwise approach. Nevertheless, our systematic review
      including a best-evidence synthesis did create order and structure in resulting
      outcomes in which a first step towards future research is generated.

PMID- 29444376
TI  - Secukinumab demonstrates high sustained efficacy and a favourable safety profile
      in patients with moderate-to-severe psoriasis through 5 years of treatment
      (SCULPTURE Extension Study).
AB  - BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively
      neutralizes IL-17A, has been shown to have significant efficacy and a favourable
      safety profile in the treatment of moderate-to-severe psoriasis and psoriatic
      arthritis. OBJECTIVE: To assess the efficacy and safety of secukinumab through 5
      years of treatment in moderate-to-severe psoriasis. METHODS: In the core
      SCULPTURE study, Psoriasis Area and Severity Index (PASI) 75 responders at Week
      12 continued receiving subcutaneous secukinumab until Year 1. Thereafter,
      patients entered the extension phase and continued treatment as per the core
      trial. Treatment was double-blinded until the end of Year 3 and open-label from
      Year 4. Here, we focus on the 300 mg fixed-interval (every 4 weeks) treatment,
      the recommended per label dose. Efficacy data are primarily reported as observed,
      but multiple imputation (MI) and last observation carried forward (LOCF)
      techniques were also undertaken as supportive analyses. RESULTS: At Year 1, 168
      patients entered the extension study and at the end of Year 5, 126 patients
      completed 300 mg (every 4 weeks) treatment. PASI 75/90/100 responses at Year 1
      (88.9%, 68.5% and 43.8%, respectively) were sustained to Year 5 (88.5%, 66.4% and
      41%). PASI responses were consistent regardless of the analysis undertaken (as
      observed, MI, or LOCF). The average improvement in mean PASI was approximately
      90% through 5 years compared with core study baseline. DLQI (dermatology life
      quality index) 0/1 response also sustained through 5 years (72.7% at Year 1 and
      65.5% at Year 5). The safety profile of secukinumab remained favourable, with no
      cumulative or unexpected safety concerns identified. CONCLUSION: Secukinumab 300
      mg treatment delivered high and sustained levels of skin clearance and improved
      quality of life through 5 years in patients with moderate-to-severe psoriasis.
      Favourable safety established in the secukinumab phase 2/3 programme was
      maintained through 5 years.

PMID- 29444377
TI  - A biomechanical analysis of prognathous and orthognathous insect head capsules:
      evidence for a many-to-one mapping of form to function.
AB  - Insect head shapes are remarkably variable, but the influences of these changes
      on biomechanical performance are unclear. Among 'basal' winged insects, such as
      dragonflies, mayflies, earwigs and stoneflies, some of the most prominent
      anatomical changes are the general mouthpart orientation, eye size and the
      connection of the endoskeleton to the head. Here, we assess these variations as
      well as differing ridge and sclerite configurations using modern engineering
      methods including multibody dynamics modelling and finite element analysis in
      order to quantify and compare the influence of anatomical changes on strain in
      particular head regions and the whole head. We show that a range of peculiar
      structures such as the genal/subgenal, epistomal and circumocular areas are
      consistently highly loaded in all species, despite drastically differing
      morphologies in species with forward-projecting (prognathous) and downward
      projecting (orthognathous) mouthparts. Sensitivity analyses show that the
      presence of eyes has a negligible influence on head capsule strain if a
      circumocular ridge is present. In contrast, the connection of the dorsal
      endoskeletal arms to the head capsule especially affects overall head loading in
      species with downward-projecting mouthparts. Analysis of the relative strains
      between species for each head region reveals that concerted changes in head
      substructures such as the subgenal area, the endoskeleton and the epistomal area
      lead to a consistent relative loading for the whole head capsule and vulnerable
      structures such as the eyes. It appears that biting-chewing loads are managed by
      a system of strengthening ridges on the head capsule irrespective of the general
      mouthpart and head orientation. Concerted changes in ridge and endoskeleton
      configuration might allow for more radical anatomical changes such as the general
      mouthpart orientation, which could be an explanation for the variability of this
      trait among insects. In an evolutionary context, many-to-one mapping of strain
      patterns onto a relatively similar overall head loading indeed could have
      fostered the dynamic diversification processes seen in insects.

PMID- 29444378
TI  - Examining relationships between total silver concentration and Sil silver
      resistance genes in domestic wastewater treatment plants.
AB  - AIMS: The overarching aims of this study were to determine if microbes found in
      wastewater treatment plants (WWTPs) carry silver resistance genes and ascertain
      whether a relationship exists between silver loading and sil silver resistance
      gene copy numbers. METHODS AND RESULTS: Activated sludge samples were collected
      from 17 WWTPs across the United States and characterized for chemical oxygen
      demand (COD) and total silver concentration. Gene copy numbers were quantified
      using qPCR for four common silver resistance genes (silC, silP, silR and silS).
      Spearman correlation analyses were performed to examine associations between
      three WWTP characteristics (i.e. size, COD and total silver concentration) and
      sil gene copy numbers. sil genes were found in all activated sludge samples,
      however the quantity of gene copy numbers was inconsistent. Of the sil genes
      screened, silS was the most abundant, followed by silR. Gene copy numbers for
      silC and silP were generally similar and overall lower than silS and silR.
      CONCLUSIONS: Neither individual or combined sil gene copy numbers correlated
      significantly with total silver concentration, suggesting either the presence of
      alternate mechanisms of silver resistance or that a critical silver concentration
      threshold within WWTPs was not met that would require specific resistance against
      silver. SIGNIFICANCE AND IMPACT OF THIS STUDY: To the authors' knowledge, this is
      one of the first studies to measure the prevalence of sil genes in engineered
      systems. Results from this study suggest that at least four silver resistance
      genes are commonly found within WWTP-activated sludge, however it is unclear if
      these genes are being expressed under current total silver loadings.

PMID- 29444379
TI  - One-Pot Generation of Bicyclo[3.1.0]hexanols and Cyclohexanones by Double
      Interrupted Nazarov Reactions.
AB  - Organoaluminum-mediated double interrupted Nazarov cyclization to access
      bicyclo[3.1.0]hexanols via nucleophilic methyl attack followed by Simmons-Smith
      type electrophilic cyclopropanation is reported. These alcohols can undergo ring
      opening to afford cyclohexanones or cyclohexenones, broadening the range of
      scaffolds available via interrupted Nazarov reaction beyond the usual
      cyclopentanoid products. Throughout the sequence, a total of four new C-C bonds
      are formed, along with four new stereogenic centers.

PMID- 29444380
TI  - A phytobeneficial strain Planomicrobium sp. MSSA-10 triggered oxidative stress
      responsive mechanisms and regulated the growth of pea plants under induced saline
      environment.
AB  - AIMS: The study was planned to characterize Planomicrobium sp. MSSA-10 for plant
      beneficial traits and to evaluate its inoculation impact on physiology of pea
      plants under different salinity levels. METHODS AND RESULTS: Strain MSSA-10 was
      isolated from pea rhizosphere and identified by the analysis of 16S rRNA gene
      sequence. The strain demonstrated phosphate solubilization and auxin production
      up to 2 mol l-1 NaCl and exhibited 1-aminocyclopropane-1-carboxylic acid
      deaminase activity up to 1.5 mol l-1 salt. In an inoculation experiment under
      different salinity regimes, a significant increase in growth was observed
      associated with decreased levels of reactive oxygen species and enhanced
      antioxidative enzyme activities. The strain also promoted the translocation of
      nutrients in plants with subsequent increase in chlorophyll and protein contents
      as compared to noninoculated plants. It has been observed that rifampicin
      resistant derivatives of MSSA-10 were able to survive for 30 days at optimum cell
      density with pea rhizosphere. CONCLUSION: Growth-stimulating effect of MSSA-10 on
      pea plants may be attributed to its rhizosphere competence, nutrient mobilization
      and modulation of plant oxidative damage repair mechanisms under saline
      environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Planomicrobium sp. MSSA-10
      might be used as potent bioinoculant to relieve pea plants from deleterious
      effects of salinity.

PMID- 29444381
TI  - Response to Tumin's letter on community social deprivation and solid organ
      transplant outcomes.

PMID- 29444382
TI  - A prospective right-left comparative study to evaluate the efficacy and
      tolerability of combination of NB-UVB and topical bimatoprost 0.03% eye drops
      versus NB-UVB given alone in patients of vitiligo vulgaris.

PMID- 29444384
TI  - Osmoadaptation of wine yeast (Saccharomyces cerevisiae) during Icewine
      fermentation leads to high levels of acetic acid.
AB  - AIMS: Volatile acidity (VA) production along with gene expression patterns,
      encoding enzymes involved in both acetic acid production and utilization, were
      investigated to relate gene expression patterns to the production of undesired VA
      during Icewine fermentation. METHODS AND RESULTS: Icewine juice and diluted
      Icewine juice were fermented using the Saccharomyces cerevisiae wine yeast K1
      V1116. Acetic acid production increased sixfold during the Icewine fermentation
      vs the diluted juice condition, while ethyl acetate production increased 2.4-fold
      in the diluted fermentation relative to the Icewine. Microarray analysis profiled
      the transcriptional response of K1-V1116 under both conditions. ACS1 and ACS2
      were downregulated 19.0-fold and 11.2-fold, respectively, in cells fermenting
      Icewine juice compared to diluted juice. ALD3 expression was upregulated 14.6
      fold, and gene expressions involved in lipid and ergosterol synthesis decreased
      during Icewine fermentation. CONCLUSIONS: Decreased expression of ACS1 and ACS2
      together with increased ALD3 expression contributes to the higher acetic acid and
      lower ethyl acetate levels generated by K1-V1116 fermenting under hyperosmotic
      stress. SIGNIFICANCE AND IMPACT OF THE STUDY: This work represents a more
      comprehensive understanding of how and why commercial wine yeast respond at the
      transcriptional and metabolic level during fermentation of Icewine juice, and how
      these responses contribute to increased acetic acid and decreased ethyl acetate
      production.

PMID- 29444383
TI  - Stemness and anti-cancer drug resistance in ATP-binding cassette subfamily G
      member 2 highly expressed pancreatic cancer is induced in 3D culture conditions.
AB  - The expression of ATP-binding cassette subfamily G member 2 (ABCG2) is related to
      tumorigenic cancer stem cells (CSC) in several cancers. However, the effects of
      ABCG2 on CSC-related malignant characteristics in pancreatic ductal
      adenocarcinoma (PDAC) are not well elucidated. In this study, we compared the
      characteristics of low (ABCG2-) and high (ABCG2+)-ABCG2-expressing PDAC cells
      after cell sorting. In adherent culture condition, human PDAC cells, PANC-1,
      contained approximately 10% ABCG2+ cell populations, and ABCG2+ cells displayed
      more and longer microvilli compared with ABCG2- cells. Unexpectedly, ABCG2+ cells
      did not show significant drug resistance against fluorouracil, gemcitabine and
      vincristine, and ABCG2- cells exhibited higher sphere formation ability and
      stemness marker expression than those of ABCG2+ cells. Cell growth and motility
      was greater in ABCG2- cells compared with ABCG2+ cells. In contrast, epithelial
      mesenchymal transition ability between ABCG2- and ABCG2+ cells was comparable. In
      3D culture conditions, spheres derived from ABCG2- cells generated a large number
      of ABCG2+ cells, and the expression levels of stemness markers in these spheres
      were higher than spheres from ABCG2+ cells. Furthermore, spheres containing large
      populations of ABCG2+ cells exhibited high resistance against anti-cancer drugs
      presumably depending on ABCG2. ABCG2+ cells in PDAC in adherent culture are not
      correlated with stemness and malignant behaviors, but ABCG2+ cells derived from
      ABCG2- cells after sphere formation have stemness characteristics and anti-cancer
      drug resistance. These findings suggest that ABCG2- cells generate ABCG2+ cells
      and the malignant potential of ABCG2+ cells in PDAC varies depending on their
      environments.

PMID- 29444385
TI  - Improving near-peer teaching quality in anatomy by educating teaching assistants:
      An example from Sweden.
AB  - Peer-assisted learning has gained momentum in a variety of disciplines, including
      medical education. In Gothenburg, Sweden, medical students who have finished
      their compulsory anatomy courses have the option of working as teaching
      assistants (TAs). Teaching assistants provide small group teaching sessions as a
      complement to lectures given by faculty. Previously, TAs were left to handle the
      role as junior teachers by themselves, but since 2011, a continuation course in
      anatomy has been developed with the aim of providing the TAs better anatomy
      knowledge and guidance for teaching. The course was designed to comprise 7.5 ECTS
      credits (equivalent to 5 weeks of full-time studies), and today all TAs are
      required to take this course before undertaking their own teaching
      responsibilities. This study aims to compare course evaluations of TA teaching
      before and after the introduction of the anatomy continuation course, in order to
      understand how students perceived teaching performed by self-learned versus
      trained TAs. The results of this study demonstrate that there was a trend towards
      better teaching performed by trained TAs. The variability in rankings decreased
      significantly after the introduction of the continuation course. This was mainly
      due to an improvement among the TAs with the lowest levels of performance. In
      addition to comparing student rankings, TAs were interviewed regarding their
      experiences and perceptions within the continuation course. The course was
      generally positively regarded. The TAs described a sense of cohesion and
      appreciation since the institute invested in a course dedicated specifically for
      them. Anat Sci Educ 11: 403-409. (c) 2018 American Association of Anatomists.

PMID- 29444386
TI  - Chemical Composition of Cacti Wood and Comparison with the Wood of Other
      Taxonomic Groups.
AB  - The aims of this study were to determine the wood chemical composition of 25
      species of Cactaceae and to relate the composition to their anatomical diversity.
      The hypothesis was that wood chemical components differ in relationship to their
      wood features. The results showed significant differences in wood chemical
      compounds across species and genera (P < 0.05). Pereskia had the highest
      percentage of lignin, whereas species of Coryphantha had the lowest; extractive
      compounds in water were highest for Echinocereus, Mammillaria, and Opuntia.
      Principal component analysis showed that lignin proportion separated the fibrous,
      dimorphic, and non-fibrous groups; additionally, the differences within each type
      of wood occurred because of the lignification of the vascular tissue and the type
      of wall thickening. Compared with other groups of species, the Cactaceae species
      with fibrous and dimorphic wood had a higher lignin percentage than did
      gymnosperms and Acer species. Lignin may confer special rigidity to tracheary
      elements to withstand desiccation without damage during adverse climatic
      conditions.

PMID- 29444387
TI  - The structure of the apo cAMP-binding domain of HCN4 - a stepping stone toward
      understanding the cAMP-dependent modulation of the hyperpolarization-activated
      cyclic-nucleotide-gated ion channels.
AB  - The hyperpolarization-activated cyclic-nucleotide-gated (HCN) ion channels
      control nerve impulse transmission and cardiac pacemaker activity. The modulation
      by cAMP is critical for the regulatory function of HCN in both neurons and
      cardiomyocytes, but the underlying mechanism is not fully understood. Here, we
      show how the structure of the apo cAMP-binding domain of the HCN4 isoform has
      contributed to a model for the cAMP-dependent modulation of the HCN ion-channel.
      This model recapitulates the structural and dynamical changes that occur along
      the thermodynamic cycle arising from the coupling of cAMP-binding and HCN self
      association equilibria. The proposed model addresses some of the questions
      previously open about the auto-inhibition of HCN and its cAMP-induced activation,
      while opening new opportunities for selectively targeting HCN through allosteric
      ligands. A remaining challenge is the investigation of HCN dimers and their
      regulatory role. Overcoming this challenge will require the integration of
      crystallography, cryo electron microscopy, NMR, electrophysiology and
      simulations.

PMID- 29444388
TI  - The virtual microscopy database-sharing digital microscope images for research
      and education.
AB  - Over the last 20 years, virtual microscopy has become the predominant modus of
      teaching the structural organization of cells, tissues, and organs, replacing the
      use of optical microscopes and glass slides in a traditional histology or
      pathology laboratory setting. Although virtual microscopy image files can easily
      be duplicated, creating them requires not only quality histological glass slides
      but also an expensive whole slide microscopic scanner and massive data storage
      devices. These resources are not available to all educators and researchers,
      especially at new institutions in developing countries. This leaves many schools
      without access to virtual microscopy resources. The Virtual Microscopy Database
      (VMD) is a new resource established to address this problem. It is a virtual
      image file-sharing website that allows researchers and educators easy access to a
      large repository of virtual histology and pathology image files. With the support
      from the American Association of Anatomists (Bethesda, MD) and MBF Bioscience
      Inc. (Williston, VT), registration and use of the VMD are currently free of
      charge. However, the VMD site is restricted to faculty and staff of research and
      educational institutions. Virtual Microscopy Database users can upload their own
      collection of virtual slide files, as well as view and download image files for
      their own non-profit educational and research purposes that have been deposited
      by other VMD clients. Anat Sci Educ 11: 510-515. (c) 2018 American Association of
      Anatomists.

PMID- 29444389
TI  - Anatomy integration: Effective change or change of affect?
AB  - Anatomy is fundamental to clinical practice, is considered a rite of passage in
      becoming a physician and is key to professional identity formation. The anatomy
      course that began the medical curriculum at the University of New Mexico School
      of Medicine was recently dissolved to address content and process gaps in the pre
      clinical curriculum. Anatomy was integrated into the organ system blocks to make
      room for new courses to address content gaps. Previous reports of anatomy
      integration document more positive attitudes and perceptions to teaching anatomy
      in context, as compared to an independent course. The current prospective study
      compared two medical student cohorts to determine the effects of teaching anatomy
      in and out of context on the cognitive and affective domains of learning. In a
      pre, post, and follow-up design, methods included content assessments, confidence
      probes, and attitude surveys informed by focus groups. Results indicated that
      anatomical knowledge and student confidence was gained and mastered in both
      curricula. Initial acquisition of content was higher in the integrated
      curriculum, but not maintained. Students in the integrated curriculum displayed a
      different relationship to learning anatomy, appearing more concerned with their
      personal progression than with the connection of anatomy to medical practice or
      patient care. These students also agreed less with statements related to working
      in teams, reflective practices and professional identity formation. Further
      studies will determine if this difference will diminish with continued exposure
      to anatomy and may inform future curricular adjustments. Anat Sci Educ. (c) 2018
      American Association of Anatomists.

PMID- 29444390
TI  - The use of alpha 2 agonists during idiopathic scoliosis repair : a narrative
      review of the literature.
AB  - Alpha 2 agonists are appreciated drugs designed for the peri-operative period,
      because of their anxiolytic, sedative and analgesic properties. However, they are
      usually avoided during scoliosis surgery, a longlasting major procedure involving
      healthy patients, because of their potential effects on Somatosensory and
      Motorevoked potentials. The absence ofrecommendations suggests that their effects
      on evoked potentials are still unclear. Thus, we tried in this narrative review
      to identify the literature representative of the effects of clonidine and
      dexmedetomidine on evoked potentials, on human beings, published between 1988 and
      2015 in English or French, using GOOGLE SCHOLAR and PUBMED. Paucity of literature
      prevented any conclusion about Clonidine's effects on evoked potentials, but no
      data suggested a noxious effect of Clonidine on evoked potentials, used in oral
      premedication (300 MUg) or during the procedure (2 to 5 MUg/kg). If literature
      was more extensive for dexmedetomidine, studies were still controversial.
      Although the majority of the studies did not find statistically significant
      differences concerning the effects of this drug on evoked potentials (loading
      dose of 0.3 to 1 MUg/ kg followed by continuous infusion of 0.3 to 0.8 MUg/kg/h),
      2 case reports and 2 studies described substantial decreases. However,
      dexmedetomidine's shorter duration of action allowed a quick return to basal
      situation within an hour. In conclusion, more studies are needed in order to
      evaluate the effects of alpha 2 agonists on evoked potentials and to assess the
      safety of their use in this setting.

PMID- 29444391
TI  - High Flow Nasal Cannula oxygenation for adult patients in the ICU: a literature
      review.
AB  - Oxygenation using High Flow Nasal Cannula (HFNC) was initially described in
      neonatal medicine, but, gradually, its use has extended to adult patients. The
      efficacy of the device has been linked to higher flows of oxygen delivered to the
      patients, air tract humidification, alveolar recruitment through a positive end
      expiratory pressure (PEEP) effect, prevention of nasopharyngeal collapse, and
      dead-space washout. Beside the fact that HFNC is a non-invasive way of delivering
      oxygen to ICU patients, and is well tolerated, results from various clinical
      trials tend to show positive outcomes for patients presenting with acute
      hypoxemic respiratory failure (AHRF), during intubation, or during the post
      extubation period. However, controversy arose from recent publications, and
      larger trials are still required to clarify the position of HFNC in the ICU, and
      help define the subgroups of patients presenting with AHRF that are most likely
      to benefit from HFNC therapy.

PMID- 29444392
TI  - Intraoperative cerebral hypoperfusion and electroencephalogram suppression
      resulting in neurological complications after cardiac surgery : the need for an
      in depth investigation.
AB  - Reports on the demographic profile of older populations estimate that, in 2050,
      19 countries will have at least 10% of their population aged 80 years or more.
      Many high risk elderly patients undergo cardiac surgery. In addition, advanced
      age has been shown to be a strong predictor of adverse neurological outcome.
      Despite sig- nificant improvements achieved in the perioperative care of cardiac
      surgical patients, neurological complications remain a global health issue.
      Recent findings have pointed out that cerebral hypoperfusion and too deep levels
      of anesthesia are major sources of adverse neurological outcomes. Cerebral near
      in-frared spectroscopy provides information about cerebral perfusion non
      invasively, and is increasingly used. Depth of anesthesia is evaluated using
      monitors that are based on processed electroencephalogram. This non-systematic
      review focuses on the results of studies performed with each monitor separately,
      and the need for a combined evaluation of their utility and eventual impact on
      neurological outcomes. The use of a combined cerebral monitoring strategy based
      on the two aforementioned monitors is proposed in order to optimize cerebral
      outcomes.

PMID- 29444393
TI  - Two different techniques of facial mask induction of anesthesia in children
      provide identical intubation conditions despite different anesthetic depth.
AB  - BACKGROUND: Sevoflurane induction in chil- dren is performed using different
      techniques. Constricted, centered, and symmetrical pupils (CCSP) are classically
      the endpoint to be achieved before laryngoscopy is performed. OBJECTIVES: We
      investigated whether two different inhalation induction techniques with the same
      clinical end- point provided similar intubating conditions and comparable depth
      of anesthesia as assessed by the Bispectral Index (BIS). METHODS: Following IRB
      approval, and informed parental consent, 20 children were recruited. They were
      sched- uled for general anesthesia with tracheal intubation, and randomly
      assigned to Group 1, where the practitioner used 6% inspired sevoflurane in 50%
      02/N20, and no manually assisted ventilation, or Group 2, where inspired
      sevoflurane was 8% in 50% 02/N20, and ventilation was manually supported upon
      loss of consciousness. BIS values were blinded. Laryngoscopy was performed after
      CCSP. Intubation conditions scoring was based on jaw relaxation (mobile = 1,
      partially mobile = 2, fixed = 3), position of vocal cords (open = 1, half-closed
      = 2, closed = 3), and cough (no cough = 1, 1 or 2 coughing efforts = 2,
      persistent coughing = 3). A total score > 3 corresponded to non-optimal
      conditions. RESULTS: Upon CCSP, BIS values were significantly lower in Group 1
      [mean (SD) : 30 (8) - 48 (18), p <0.001], despite significantly higher end-tidal
      sevoflurane concentration in Group 2 [mean (SD) : 5.0 (0.7) - 6.2 (0.5) ; p
      <0.001]. Time to CCSP was slightly shorter in Group 2. Intubation conditions were
      always optimal except for one patient of Group 1. DISCUSSION: Both induction
      techniques achieve good intubating conditions. Possible explanations for the
      between-group BIS difference include variable appreciation of the CCSP endpoint,
      different induction lengths or sevoflurane equilibration times, or sevoflurane
      induced increase in electroencephalogram power. A better indicator of the best
      time to intubate is needed to avoid too deep anesthesia in children.

PMID- 29444394
TI  - Hearing loss after spinal anesthesia : A comparative prospective randomized
      cohort study.
AB  - OBJECTIVE: In this comparative randomized cohort study, we aimed at evaluating
      the occurrence of sensorineural hearing loss after general and spinal anesthesia
      using both subjective and objective tests. MATERIAL AND METHODS: Fifty patients
      scheduled for elective cesarean section were approached, of which 21 patients
      received spinal anesthesia (group S), and 16 patients received general anesthesia
      (group G). In group S, a 27 G pencil point spinal needle was used. Pure tone
      audiometry and Distortion Product OtoAcoustic Emissions (DPOAE) were performed
      before and 48 hours after surgery. RESULTS: No between-group significant
      difference in pre and postoperative audiometric hearing threshold and pure tone
      average value were noticed, as well as in pre and postoperative DPOAE amplitude
      and signal-to-noise ratio (SNR). CONCLUSION: In this study, we did not observe
      any hearing loss after cesarean section under general or spinal anesthesia. Using
      the non-traumatic 27 gauge pencil point needle for performing spinal anesthesia
      does not seem to be associated with a risk of hearing loss, similarly to general
      anesthesia.

PMID- 29444395
TI  - A cardiac arrest following the administration of succinylcholine.
AB  - A twenty-three year old woman, admitted to the intensive care unit (ICU) with a
      diagnosis of menin- gitis and associated lower limb ischemia suffered a car- diac
      arrest, due to extreme hyperkalemia, following the administration of
      succinylcholine in order to replace an endo-tracheal tube. After prolonged
      cardiopulmonary resuscitation (CPR) lasting 45 minutes, during which 8 mg of
      epinephrine was administered, cardiac output was restored. Four weeks later the
      patient left intensive care, having made a full recovery with no neurological
      deficit. The following case highlights the risks of succinylcholine in the septic
      patient and that prolonged resuscitation can have a succesfiil outcome.

PMID- 29444396
TI  - Integrating a Silicon Solar Cell with a Triboelectric Nanogenerator via a Mutual
      Electrode for Harvesting Energy from Sunlight and Raindrops.
AB  - Solar cells, as promising devices for converting light into electricity, have a
      dramatically reduced performance on rainy days. Here, an energy harvesting
      structure that integrates a solar cell and a triboelectric nanogenerator (TENG)
      device is built to realize power generation from both sunlight and raindrops. A
      heterojunction silicon (Si) solar cell is integrated with a TENG by a mutual
      electrode of a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)
      (PEDOT:PSS) film. Regarding the solar cell, imprinted PEDOT:PSS is used to reduce
      light reflection, which leads to an enhanced short-circuit current density. A
      single-electrode-mode water-drop TENG on the solar cell is built by combining
      imprinted polydimethylsiloxane (PDMS) as a triboelectric material combined with a
      PEDOT:PSS layer as an electrode. The increasing contact area between the
      imprinted PDMS and water drops greatly improves the output of the TENG with a
      peak short-circuit current of ~33.0 nA and a peak open-circuit voltage of ~2.14
      V, respectively. The hybrid energy harvesting system integrated electrode
      configuration can combine the advantages of high current level of a solar cell
      and high voltage of a TENG device, promising an efficient approach to collect
      energy from the environment in different weather conditions.

PMID- 29444397
TI  - Partner-Specific Prediction of Protein-Dimer Stability from Unbound Structure of
      Monomer.
AB  - Protein complexes play deterministic roles in live entities in sensing,
      compiling, controlling, and responding to external and internal stimuli.
      Thermodynamic stability is an important property of protein complexes; having
      knowledge about complex stability helps us to understand the basics of protein
      assembly-related diseases and the mechanism of protein assembly clearly. Enormous
      protein-protein interactions, detected by high-throughput methods, necessitate
      finding fast methods for predicting the stability of protein assemblies in a
      quantitative and qualitative manner. The existing methods of predicting complex
      stability need knowledge about the three-dimensional (3D) structure of the
      intended protein complex. Here, we introduce a new method for predicting
      dissociation free energy of subunits by analyzing the structural and topological
      properties of a protein binding patch on a single subunit of the desired protein
      complex. The method needs the 3D structure of just one subunit and the
      information about the position of the intended binding site on the surface of
      that subunit to predict dimer stability in a classwise manner. The patterns of
      structural and topological properties of a protein binding patch are decoded by
      recurrence quantification analysis. Nonparametric discrimination is then utilized
      to predict the stability class of the intended dimer with accuracy greater than
      85%.

PMID- 29444398
TI  - The Importance of Cell Shape Sampling To Accurately Predict Flexibility in Metal
      Organic Frameworks.
AB  - In this work, the influence of cell shape sampling on the predicted stability of
      the different metastable phases in flexible metal-organic frameworks at finite
      temperatures is investigated. The influence on the free energy by neglecting cell
      shape sampling is quantified for the prototypical MIL-53(Al) and the topical DUT
      49(Cu). This goal is achieved by constructing free energy profiles in ensembles
      either in which the phase space associated with the cell shape is sampled
      explicitly or in which the cell shape is kept fixed. When neglecting cell shape
      sampling, thermodynamic integration of the hydrostatic pressure yields unreliable
      free energy profiles that depend on the choice of the fixed cell shape. In this
      work, we extend the thermodynamic integration procedure via the introduction of a
      generalized pressure, derived from the Lagrangian strain tensor and the second
      Piola-Kirchhoff tensor. Using this generalized procedure, the dependence on the
      unit cell shape can be eliminated, and the inaccuracy in free energy stemming
      from the lack of cell shape sampling can be uniquely quantified. Finally, it is
      shown that the inaccuracy in free energy when fixing the cell shape at room
      temperature stems mainly from entropic contributions for both MIL-53(Al) and DUT
      49(Cu).

PMID- 29444399
TI  - Chemical Understanding of the Limited Site-Specificity in Molecular Inner-Shell
      Photofragmentation.
AB  - In many cases fragmentation of molecules upon inner-shell ionization is very
      unspecific with respect to the initially localized ionization site. Often this
      finding is interpreted in terms of an equilibration of internal energy into
      vibrational degrees of freedom after Auger decay. We investigate the X-ray
      photofragmentation of ethyl trifluoroacetate upon core electron ionization at
      environmentally distinct carbon sites using photoelectron-photoion-photoion
      coincidence measurements and ab initio electronic structure calculations. For all
      four carbon ionization sites, the Auger decay weakens the same bonds and
      transfers the two charges to opposite ends of the molecule, which leads to a
      rapid dissociation into three fragments, followed by further fragmentation steps.
      The lack of site specificity is attributed to the character of the dicationic
      electronic states after Auger decay instead of a fast equilibration of internal
      energy.

PMID- 29444400
TI  - Chiral Nickel(II) Complex Catalyzed Enantioselective Doyle-Kirmse Reaction of
      alpha-Diazo Pyrazoleamides.
AB  - Although high enantioselectivity of [2,3]-sigmatropic rearrangement of sulfonium
      ylides (Doyle-Kirmse reaction) has proven surprisingly elusive using classic
      chiral Rh(II) and Cu(I) catalysts, in principle it is due to the difficulty in
      fine discrimination of the heterotopic lone pairs of sulfur and chirality
      inversion at sulfur of sulfonium ylides. Here, we show that the synergistic
      merger of new alpha-diazo pyrazoleamides and a chiral N, N'-dioxide-nickel(II)
      complex catalyst enables a highly enantioselective Doyle-Kirmse reaction. The
      pyrazoleamide substituent serves as both an activating and a directing group for
      the ready formation of a metal-carbene- and Lewis-acid-bonded ylide intermediate
      in the assistance of a dual-tasking nickel(II) complex. An alternative chiral
      Lewis-acid-bonded ylide pathway greatly improves the product enantiopurity even
      for the reaction of a symmetric diallylsulfane. The majority of transformations
      over a series of aryl- or vinyl-substituted alpha-diazo pyrazoleamindes and
      sulfides proceed rapidly (within 5-20 min in most cases) with excellent results
      (up to 99% yield and 96% ee), providing a breakthrough in enantioselective Doyle
      Kirmse reaction.

PMID- 29444401
TI  - Modulating Electrocatalysis on Graphene Heterostructures: Physically Impermeable
      Yet Electronically Transparent Electrodes.
AB  - The electronic properties and extreme thinness of graphene make it an attractive
      platform for exploring electrochemical interactions across dissimilar
      environments. Here, we report on the systematic tuning of the electrocatalytic
      activity toward the oxygen reduction reaction (ORR) via heterostructures formed
      by graphene modified with a metal underlayer and an adlayer consisting of a
      molecular catalyst. Systematic voltammetric testing and electrochemical imaging
      of patterned electrodes allowed us to confidently probe modifications on the ORR
      mechanisms and overpotential. We found that the surface configuration largely
      determined the ORR mechanism, with adlayers of porphyrin molecular catalysts
      displaying a higher activity for the 2e- pathway than the bare basal plane of
      graphene. Surprisingly, however, the underlayer material contributed
      substantially to lower the activation potential for the ORR in the order Pt > Au
      > SiO x, strongly suggesting the involvement of the solution-excluded metal on
      the reaction. Computational investigations suggest that ORR enhancements
      originate from permeation of metal d-subshell electrons through the graphene
      layer. In addition, these physically impermeable but electronically transparent
      electrodes displayed tolerance to cyanide poisoning and stability toward long
      term cycling, highlighting graphene as an effective protection layer of noble
      metal while enabling electrochemical interactions. This work has implications in
      the mechanistic understanding of 2D materials and core-shell-type
      heterostructures for electrocatalytic reactions.

PMID- 29444402
TI  - Solid-Phase Synthesis of Pyrrole Derivatives through a Multicomponent Reaction
      Involving Lys-Containing Peptides.
AB  - The synthesis of pyrroles has received considerable attention because of their
      biological and pharmaceutical activities. Herein we describe a solid-phase
      multicomponent reaction that utilizes Lys as a N donor, beta-nitrostyrenes, 1,3
      dicarbonyl compounds, and FeCl3 as an easily accessible catalyst under microwave
      irradiation to afford the subsequent pyrrole derivatives in high conversions. The
      strategy combines three of the most powerful tools in modern synthetic chemistry:
      the solid-phase mode, microwave activation, and a multicomponent reaction. The
      excellent results in terms of rapidity, versatility, and purity obtained herein
      support once again that this combined strategy is efficient for gaining chemical
      diversity.

PMID- 29444404
TI  - Polarizable Density Embedding Coupled Cluster Method.
AB  - We present the theory and implementation of the polarizable density embedding
      (PDE) model in combination with coupled cluster (CC) theory (PDE-CC). This model
      has been implemented in the Dalton quantum chemistry program by adapting the CC
      code to the polarizable embedding library ( PElib). In the PDE-CC method, the
      smaller, but chemically important core region is described with a high-level CC
      method. The environment surrounding the core region can be separated into two
      levels of description: an inner and an outer region. The effect of the inner
      region on the core region is described by an embedding potential consisting of a
      set of fragment densities obtained from calculations on isolated fragments with a
      quantum-chemistry method such as Hartree-Fock (HF) or Kohn-Sham density
      functional theory (KS-DFT) and dressed with a set of atom-centered anisotropic
      dipole-dipole polarizabilities. The outer region consists of distributed atom
      centered multipoles and polarizabilities, i.e., in the same way as in the
      polarizable embedding (PE) model. The PDE-CC method contains embedding potential
      operators that account for the electrostatic and polarization interactions
      between the core region and the environment, as well as for nonelectrostatic
      (also known as Pauli and exchange) repulsion. All environmental effects are
      included through one-electron operators and account very efficiently for the
      response of the environment due to the change in the electron density of the core
      region, e.g., upon an electronic transition.

PMID- 29444403
TI  - Plant Villin Headpiece Domain Demonstrates a Novel Surface Charge Pattern and
      High Affinity for F-Actin.
AB  - Plants utilize multiple isoforms of villin, an F-actin regulating protein with an
      N-terminal gelsolin-like core and a distinct C-terminal headpiece domain. Unlike
      their vertebrate homologues, plant villins have a much longer linker polypeptide
      connecting the core and headpiece. Moreover, the linker-headpiece connection
      region in plant villins lacks sequence homology to the vertebrate villin
      sequences. It is unknown to what extent the plant villin headpiece structure and
      function resemble those of the well-studied vertebrate counterparts. Here we
      present the first solution NMR structure and backbone dynamics characterization
      of a headpiece from plants, villin isoform 4 from Arabidopsis thaliana. The
      villin 4 headpiece is a 63-residue domain (V4HP63) that adopts a typical
      headpiece fold with an aromatics core and a tryptophan-centered hydrophobic cap
      within its C-terminal subdomain. However, V4HP63 has a distinct N-terminal
      subdomain fold as well as a novel, high mobility loop due to the insertion of
      serine residue in the canonical sequence that follows the variable length loop in
      headpiece sequences. The domain binds actin filaments with micromolar affinity,
      like the vertebrate analogues. However, the V4HP63 surface charge pattern is
      novel and lacks certain features previously thought necessary for high-affinity F
      actin binding. Utilizing the updated criteria for strong F-actin binding, we
      predict that the headpiece domains of all other villin isoforms in A. thaliana
      have high affinity for F-actin.

PMID- 29444405
TI  - Fullerene-Functionalized Monolayer-Protected Silver Clusters: [Ag29(BDT)12(C60)
      n]3- ( n = 1-9).
AB  - We report the formation of supramolecular adducts between monolayer-protected
      noble metal nanoclusters and fullerenes, specifically focusing on a well-known
      silver cluster, [Ag29(BDT)12]3-, where BDT is 1,3-benzenedithiol. We demonstrate
      that C60 molecules link with the cluster at specific locations and protect the
      fragile cluster core, enhancing the stability of the cluster. A combination of
      studies including UV-vis, high-resolution electrospray ionization mass
      spectrometry, collision-induced dissociation, and nuclear magnetic resonance
      spectroscopy revealed structural details of the fullerene-functionalized
      clusters, [Ag29(BDT)12(C60) n]3- ( n = 1-9). Density functional theory (DFT)
      calculations and molecular docking simulations affirm compatibility between the
      cluster and C60, resulting in its attachment at specific positions on the surface
      of the cluster, stabilized mainly by pi-pi and van der Waals interactions. The
      structures have also been confirmed from ion mobility mass spectrometry by
      comparing the experimental collision cross sections (CCSs) with the theoretical
      CCSs of the DFT-optimized structures. The gradual evolution of the structures
      with an increase in the number of fullerene attachments to the cluster has been
      investigated. Whereas the structure for n = 4 is tetrahedral, that of n = 8 is a
      distorted cube with a cluster at the center and fullerenes at the vertices.
      Another fullerene, C70, also exhibited similar behavior. Modified clusters are
      expected to show interesting properties.

PMID- 29444406
TI  - Limononic Acid Oxidation by Hydroxyl Radicals and Ozone in the Aqueous Phase.
AB  - Kinetics and mechanism of limononic acid (3-isopropenyl-6-oxoheptanoic acid, LA)
      oxidation by hydroxyl radicals (OH) and ozone (O3) were studied in the aqueous
      phase at 298 +/- 2 K. These reactions were investigated using liquid
      chromatography coupled to the electrospray ionization and quadrupole tandem mass
      spectrometry (LC-ESI/MS/MS). The rate coefficients determined for LA + OH
      reaction were: 1.3 +/- 0.3 * 1010 M-1 s-1 at pH = 2 and 5.7 +/- 0.6 * 109 M-1 s-1
      at pH = 10. The rate coefficient determined for LA ozonolysis was 4.2 +/- 0.2 *
      104 M-1 s-1 at pH = 2. The calculated Henry's law constant (H) for LA was ca. 6.3
      * 106 M * atm-1, thereby indicating that in fogs and clouds with LWC = 0.3-0.5 g
      * m-3 LA will reside entirely in the aqueous phase. Calculated atmospheric
      lifetimes due to reaction with OH and O3 strongly indicate that aqueous-phase
      oxidation can be important for LA under realistic atmospheric conditions. Under
      acidic conditions, the aqueous-phase oxidation of LA by OH will dominate over
      reaction with O3, whereas the opposite is more likely when pH >= 4.5. The aqueous
      phase oxidation of LA produced keto-limononic acid and a number of low-volatility
      products, such as hydroperoxy-LA and alpha-hydroxyhydroperoxides.

PMID- 29444407
TI  - Phase-Tunable Josephson Thermal Router.
AB  - A fundamental aspect of electronics is the ability to distribute a charge current
      among different terminals. On the other hand, despite the great interest in
      dissipation, storage, and conversion of heat in solid state structures, the
      control of thermal currents at the nanoscale is still in its infancy. Here, we
      show the experimental realization of a phase-tunable thermal router able to
      control the spatial distribution of an incoming heat current, thus providing the
      possibility of tuning the electronic temperatures of two output terminals. This
      ability is obtained thanks to a direct current superconducting quantum
      interference device (dc SQUID), which can tune the coherent component of the
      electronic heat currents flowing through its Josephson junctions. By varying the
      external magnetic flux and the bath temperature, the SQUID allows us to regulate
      the size and the direction of the thermal gradient between two drain electrodes.
      Our results offer new opportunities for all microcircuits requiring an accurate
      energy management, including electronic coolers, quantum information
      architectures, and thermal logic components.

PMID- 29444408
TI  - Simple Models for Difficult Electronic Excitations.
AB  - We present a single-determinant approach to three challenging topics in the
      chemistry of excited states: double excitations, charge-transfer states, and
      conical intersections. The results are obtained by using the Initial Maximum
      Overlap Method (IMOM) which is a modified version of the Maximum Overlap Method
      (MOM). The new algorithm converges better than the original, especially for these
      difficult problems. By considering several case studies, we show that a single
      determinant framework provides a simple and accurate alternative for modeling
      excited states in cases where other low-cost methods, such as CIS and TD-DFT,
      either perform poorly or fail completely.

PMID- 29444409
TI  - Sequence-Specific Self-Assembly of Positive and Negative Monomers with
      Cucurbit[8]uril Linkers.
AB  - The self-assembly into dynamic oligomers of Cucurbit[8]uril (CB[8]), a positive
      ditopic Ir(III) bis-terpyridine complex, and a negative ditopic Fe(II) bis
      terpyridine complex flanked by four butyrate side chains was assessed to answer a
      seemingly straightforward question: does CB[8] adopt a social self-sorting
      pattern by encapsulating both positive and negative units into a heteroternary
      complex? We showed that this is indeed the case, with CB[8] linking a positive Ir
      unit to a neighboring negative Fe unit whenever possible. Furthermore, the
      solubility of the dynamic oligomers was significantly affected by their sequence;
      upon addition of 0.6-1.2 equiv of positive Ir oligomer to its negative Fe
      counterpart, the predominant assembly present in solution was a mixed oligomer
      with a (Fe-Ir-Ir-) n sequence. Weak interactions between the negative butyrate
      side chains and the partially positive outer wall of CB[7] were also identified
      by two-dimensional nuclear magnetic resonance techniques, and resulted in a
      negative p Ka shift (0.10 p Ka unit) for the terminal carboxylic groups.

PMID- 29444410
TI  - Enhanced Ion Transmission Efficiency up to m/ z 24 000 for MALDI Protein Imaging
      Mass Spectrometry.
AB  - The molecular identification of species of interest is an important part of an
      imaging mass spectrometry (IMS) experiment. The high resolution accurate mass
      capabilities of Fourier transform ion cyclotron resonance mass spectrometry (FT
      ICR MS) have recently been shown to facilitate the identification of proteins in
      matrix-assisted laser desorption/ionization (MALDI) IMS. However, these
      experiments are typically limited to proteins giving rise to ions of relatively
      low m/ z due to difficulties transmitting and measuring large molecular weight
      ions of low charge states. Herein we have modified the source gas manifold of a
      commercial MALDI FT-ICR MS to regulate the gas flow and pressure to maximize the
      transmission of large m/ z protein ions through the ion funnel region of the
      instrument. By minimizing the contribution of off-axis gas disruption to ion
      focusing and maximizing the effective potential wall confining the ions through
      pressure optimization, the signal-to-noise ratios (S/N) of most protein species
      were improved by roughly 1 order of magnitude compared to normal source
      conditions. These modifications enabled the detection of protein standards up to
      m/ z 24 000 and the detection of proteins from tissue up to m/ z 22 000 with good
      S/N, roughly doubling the mass range for which high quality protein ion images
      from rat brain and kidney tissue could be produced. Due to the long time-domain
      transients (>4 s) required to isotopically resolve high m/ z proteins, we have
      used these data as part of an FT-ICR IMS-microscopy data-driven image fusion
      workflow to produce estimated protein images with both high mass and high spatial
      resolutions.

PMID- 29444411
TI  - Understanding Brain Functions in Children with Sleep-disordered Breathing.

PMID- 29444412
TI  - Heart rate variability responses to acute and repeated postexercise sauna in
      trained cyclists.
AB  - Short- to medium-term (i.e., 4-14 days) heating protocols induce physiological
      adaptations including improved cardiac autonomic modulations, as assessed using
      heart rate variability, which may contribute to greater exercise performance.
      Whether similar cardiac autonomic changes occur during an intense heating
      protocol (sauna) reported to increase plasma volume in athletes remains to be
      confirmed. This study examined changes in heart rate and its variability during a
      single extreme heat (sauna) exposure and repeated exposures in athletes. Six well
      trained male cyclists undertook sauna bathing (30 min, 87  degrees C, 11%
      relative humidity) immediately after normal training over 10 consecutive days.
      Heart rate recordings were obtained during each sauna bout. Heart rate and its
      variability (natural logarithm of root mean square of successive differences,
      lnRMSSD) were analysed during 10-min periods within the first bout, and changes
      in heart rate and lnRMSSD were analysed during each bout via magnitude-based
      inferences. During the first sauna bout, heart rate was almost certainly
      increased (~32%, effect size 1.68) and lnRMSSD was almost certainly reduced
      (~62%, effect size -5.21) from the first to the last 10-min period, indicating
      reduced parasympathetic and (or) enhanced sympathetic modulations. Acute exposure
      to extreme heat stress via sauna produced alterations in heart rate and cardiac
      autonomic modulations with successive postexercise heat exposures producing
      unclear changes over a 10-day period. The physiological benefits of intense
      heating via sauna on cardiac control in athletes remain to be elucidated.

PMID- 29444413
TI  - Involvement of Alveolar Epithelial Cell Necroptosis in Idiopathic Pulmonary
      Fibrosis Pathogenesis.
AB  - Alveolar epithelial cell (AEC) injury leading to cell death is involved in the
      process of fibrosis development during idiopathic pulmonary fibrosis (IPF). Among
      regulated/programmed cell death, the excessive apoptosis of AECs has been widely
      implicated in IPF pathogenesis. Necroptosis is a type of regulated/programmed
      necrosis. A multiprotein complex composed of receptor-interacting protein kinase
      (RIPK)-1 and -3 plays a key regulatory role in initiating necroptosis. Although
      necroptosis participates in disease pathogeneses through the release of damage
      associated molecular patterns, its association with IPF progression remains
      elusive. In this study, we attempted to illuminate the involvement of RIPK3
      regulated necroptosis in IPF pathogenesis. IPF lung tissues were used to detect
      necroptosis, and the role of RIPK3 was determined using cell culturing models of
      AECs. Lung fibrosis models of bleomycin (BLM) treatment were also used. RIPK3
      expression levels were increased in IPF lungs, and both apoptosis and necroptosis
      were detected mainly in AECs. Necrostatin-1 and RIPK3 knockout experiments in
      AECs revealed the participation of necroptosis in BLM and hydrogen peroxide
      induced cell death. BLM treatment induced RIPK3 expression in AECs and increased
      high-mobility group box 1 and IL-1beta levels in mouse lungs. The efficient
      attenuation of BLM-induced lung inflammation and fibrosis was determined in RIPK3
      knockout mice and by necrostatin-1 with a concomitant reduction in high-mobility
      group box 1 and IL-1beta. RIPK3-regulated necroptosis in AECs is involved in the
      mechanism of lung fibrosis development through the release of damage-associated
      molecular patterns as part of the pathogenic sequence of IPF.

PMID- 29444414
TI  - No individual or combined effects of caffeine and beetroot-juice supplementation
      during submaximal or maximal running.
AB  - Dietary supplements such as caffeine and beetroot juice are used by athletes in
      an attempt to optimize performance and therefore gain an advantage in
      competition. The aim of this study was to investigate the individual and combined
      effects of caffeine and beetroot-juice supplementation during submaximal and
      maximal treadmill running. Seven males (maximal oxygen uptake: 59.0 +/- 2.9 mL.kg
      1.min-1) and 2 females (maximal oxygen uptake: 53.1 +/- 11.4 mL.kg-1.min-1)
      performed a preliminary trial followed by 4 experimental test sessions. Each test
      session consisted of two 5-min submaximal running bouts (at ~70% and 80% of
      maximal oxygen uptake) and a maximal 1-km time trial (TT) in a laboratory.
      Participants ingested 70 mL of concentrated beetroot juice containing either 7.3
      mmol of nitrate (BR) or no nitrate (PBR) 2.5 h prior to each test session, then
      either caffeine (C) at 4.8 +/- 0.4 (4.3-5.6) mg/kg of body mass or a caffeine
      placebo (PC) 45 min before each test session. The 4 test sessions (BR-C, BR-PC,
      PBR-C, and PBR-PC) were presented in a counterbalanced and double-blind manner.
      No significant differences were identified between the 4 interventions regarding
      relative oxygen uptake, running economy, respiratory exchange ratio, heart rate
      (HR), or rating of perceived exertion (RPE) at the 2 submaximal intensities (P >
      0.05). Moreover, there were no significant differences in performance, maximum
      HR, peak blood lactate concentration, or RPE during the maximal TT when comparing
      the interventions (P > 0.05). In conclusion, no beneficial effects of
      supplementing with typical doses of caffeine, beetroot juice, or a combination of
      the two were observed for physiological, perceptual, or performance responses
      during submaximal or maximal treadmill running exercise.

PMID- 29444415
TI  - BACE1 Inhibition by Genistein: Biological Evaluation, Kinetic Analysis, and
      Molecular Docking Simulation.
AB  - beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) plays a role in
      generating amyloid beta (Abeta), thus playing a major part early in the
      pathogenesis of Alzheimer's disease (AD). BACE1 has emerged as a crucial
      therapeutic target for decreasing the Abeta concentration in the AD brain. To
      explore natural BACE1 inhibitors, the present study concentrated on isoflavones,
      including genistein, formononetin, glycitein, daidzein, and puerarin. In this
      study, in vitro anti-AD activities were assessed using BACE1 inhibition assays,
      as well as enzyme kinetic predictions. Molecular docking analysis was applied to
      design potential BACE1 inhibitors. Among the major isoflavones, genistein exerted
      a notable BACE1 inhibition through reversible noncompetitive mechanism, while
      other compounds were less potent against BACE1. The docking study revealed that
      genistein had negative binding energy (-8.5 kcal/mol) and was stably positioned
      in the allosteric domains of BACE1 residues. It interacted with important amino
      acid residues in BACE1, such as ASN37, GLN73, and TRP76, through hydrogen
      bonding. The results suggested that genistein may be beneficial for preventing
      and/or treating AD. Furthermore, it may provide potential guidelines for the
      design of new BACE1 inhibitors.

PMID- 29444416
TI  - Structural changes in the cell envelope of Yarrowia lipolytica yeast under stress
      conditions.
AB  - Ultrastructural changes in the cell envelope of the yeast Yarrowia lipolytica as
      a stress response were examined using electron microscopy. The formation of new
      cellular surface structures, including membrane vesicles, pore channels, and wall
      surface globules, were shown for the first time under conditions of oxidative
      (endogenous and exogenous) or thermal stress. This demonstrates once again that
      under stress conditions the microorganisms reveal properties previously unknown
      for them. Particularly noteworthy is the accumulation of silicon in the surface
      globules, which was revealed by X-ray microanalysis of the elemental composition
      of thin sections of cells. A multilayered plasmalemma instead of a 3-layered one
      is also characteristic for stressed cells. The envelope modifications above were
      observed only as a stress response and were not detected in stationary-growth
      phase yeast cells that assume different physiological states. A decrease in the
      intracellular level of cAMP allows us to assume that a common factor activates
      defensive mechanisms thus explaining the similarity of the response under
      different stress conditions. The data presented not only enable visualization of
      the yeast stress response and add to our awareness of the diversity of adaptive
      reactions, but they also raise questions about the interrelations of the stress
      phenomena and their functional necessity in the cell.

PMID- 29444417
TI  - A study on the regenerative effect of platelet-rich plasma on experimentally
      induced hepatic damage in albino rats.
AB  - Hepatic fibrosis is a worldwide health problem with significant morbidity and
      mortality. Currently, there is no effective therapy for hepatic fibrosis. The
      present study was aimed to evaluate the possible regenerative effect of platelet
      rich plasma (PRP) against thioacetamide (TAA)-induced hepatic damage. Eighty
      albino rats were included; 40 were used for PRP preparation and 40 were randomly
      divided into 4 groups: group I (control group); group II (PRP control); group III
      (TAA-intoxicated by a dose of 200 mg/kg body mass, intraperitoneally, twice
      weekly for 7 weeks), and group IV (TAA intoxicated + PRP treated). Macrophage
      inflammatory protein-1alpha (MIP-1alpha) and cyclic adenosine monophosphate
      (cAMP) were immunoassayed in addition to peroxinitrite level, NADPH-quinone
      oxidoreductase-1 (NQO1) enzyme activity, and liver function. PRP treatment showed
      significant improvement in hepatic function, and decreased MIP-1alpha and
      peroxinitrite levels. Meanwhile, significant increase in NQO1 enzyme activity and
      cAMP level were observed. The histopathological results confirmed the laboratory
      results with improvement of hepatic architecture except for some inflammatory
      cellular infiltrates. This study shows that PRP has the ability to protect
      against TAA-induced liver damage, possibly by improving redox status, liver
      histopathological architecture, and disruption of the inflammatory and fibrotic
      response induced by TAA.

PMID- 29444418
TI  - Circuitry Rewiring Directly Couples Competence to Predation in the Gut Dweller
      Streptococcus salivarius.
AB  - Small distortions in transcriptional networks might lead to drastic phenotypical
      changes, especially in cellular developmental programs such as competence for
      natural transformation. Here, we report a pervasive circuitry rewiring for
      competence and predation interplay in commensal streptococci. Canonically, in
      streptococci paradigms such as Streptococcus pneumoniae and Streptococcus mutans,
      the pheromone-based two-component system BlpRH is a central node that
      orchestrates the production of antimicrobial compounds (bacteriocins) and
      incorporates signal from the competence activation cascade. However, the human
      commensal Streptococcus salivarius does not contain a functional BlpRH pair,
      while the competence signaling system ComRS directly couples bacteriocin
      production and competence commitment. This network shortcut might underlie an
      optimal adaptation against microbial competitors and explain the high prevalence
      of S. salivarius in the human digestive tract. Moreover, the broad spectrum of
      bacteriocin activity against pathogenic bacteria showcases the commensal and
      genetically tractable S. salivarius species as a user-friendly model for
      competence and bacterial predation.

PMID- 29444419
TI  - Pak1 Kinase Maintains Apical Membrane Identity in Epithelia.
AB  - Epithelial cells are polarized along their apical-basal axis by the action of the
      small GTPase Cdc42, which is known to activate the aPKC kinase at the apical
      domain. However, loss of aPKC kinase activity was reported to have only mild
      effects on epithelial cell polarity. Here, we show that Cdc42 also activates a
      second kinase, Pak1, to specify apical domain identity in Drosophila and
      mammalian epithelia. aPKC and Pak1 phosphorylate an overlapping set of polarity
      substrates in kinase assays. Inactivating both aPKC kinase activity and the Pak1
      kinase leads to a complete loss of epithelial polarity and morphology, with cells
      losing markers of apical polarization such as Crumbs, Par3/Bazooka, or ZO-1. This
      function of Pak1 downstream of Cdc42 is distinct from its role in regulating
      integrins or E-cadherin. Our results define a conserved dual-kinase mechanism for
      the control of apical membrane identity in epithelia.

PMID- 29444420
TI  - Perineurial Barrier Glia Physically Respond to Alcohol in an Akap200-Dependent
      Manner to Promote Tolerance.
AB  - Ethanol is the most common drug of abuse. It exerts its behavioral effects by
      acting on widespread neural circuits; however, its impact on glial cells is less
      understood. We show that Drosophila perineurial glia are critical for ethanol
      tolerance, a simple form of behavioral plasticity. The perineurial glia form the
      continuous outer cellular layer of the blood-brain barrier and are the interface
      between the brain and the circulation. Ethanol tolerance development requires the
      A kinase anchoring protein Akap200 specifically in perineurial glia. Akap200
      tightly coordinates protein kinase A, actin, and calcium signaling at the
      membrane to control tolerance. Furthermore, ethanol causes a structural
      remodeling of the actin cytoskeleton and perineurial membrane topology in an
      Akap200-dependent manner, without disrupting classical barrier functions. Our
      findings reveal an active molecular signaling process in the cells at the blood
      brain interface that permits a form of behavioral plasticity induced by ethanol.

PMID- 29444421
TI  - Chloroplast Signaling Gates Thermotolerance in Arabidopsis.
AB  - Temperature is a key environmental variable influencing plant growth and
      survival. Protection against high temperature stress in eukaryotes is coordinated
      by heat shock factors (HSFs), transcription factors that activate the expression
      of protective chaperones such as HEAT SHOCK PROTEIN 70 (HSP70); however, the
      pathway by which temperature is sensed and integrated with other environmental
      signals into adaptive responses is not well understood. Plants are exposed to
      considerable diurnal variation in temperature, and we have found that there is
      diurnal variation in thermotolerance in Arabidopsis thaliana, with maximal
      thermotolerance coinciding with higher HSP70 expression during the day. In a
      forward genetic screen, we identified a key role for the chloroplast in
      controlling this response, suggesting that light-induced chloroplast signaling
      plays a key role. Consistent with this, we are able to globally activate binding
      of HSFA1a to its targets by altering redox status in planta independently of a
      heat shock.

PMID- 29444422
TI  - Netrin-1 Confines Rhombic Lip-Derived Neurons to the CNS.
AB  - During brainstem development, newborn neurons originating from the rhombic lip
      embark on exceptionally long migrations to generate nuclei important for
      audition, movement, and respiration. Along the way, this highly motile population
      passes several cranial nerves yet remains confined to the CNS. We found that Ntn1
      accumulates beneath the pial surface separating the CNS from the PNS, with gaps
      at nerve entry sites. In mice null for Ntn1 or its receptor DCC, hindbrain
      neurons enter cranial nerves and migrate into the periphery. CNS neurons also
      escape when Ntn1 is selectively lost from the sub-pial region (SPR), and
      conversely, expression of Ntn1 throughout the mutant hindbrain can prevent their
      departure. These findings identify a permissive role for Ntn1 in maintaining the
      CNS-PNS boundary. We propose that Ntn1 confines rhombic lip-derived neurons by
      providing a preferred substrate for tangentially migrating neurons in the SPR,
      preventing their entry into nerve roots.

PMID- 29444423
TI  - Nuclear Organization in the Spinal Cord Depends on Motor Neuron Lamination
      Orchestrated by Catenin and Afadin Function.
AB  - Motor neurons in the spinal cord are found grouped in nuclear structures termed
      pools, whose position is precisely orchestrated during development. Despite the
      emerging role of pool organization in the assembly of spinal circuits, little is
      known about the morphogenetic programs underlying the patterning of motor neuron
      subtypes. We applied three-dimensional analysis of motor neuron position to
      reveal the roles and contributions of cell adhesive function by inactivating N
      cadherin, catenin, and afadin signaling. Our findings reveal that nuclear
      organization of motor neurons is dependent on inside-out positioning,
      orchestrated by N-cadherin, catenin, and afadin activities, controlling cell body
      layering on the medio-lateral axis. In addition to this lamination-like program,
      motor neurons undergo a secondary, independent phase of organization. This
      process results in segregation of motor neurons along the dorso-ventral axis of
      the spinal cord, does not require N-cadherin or afadin activity, and can proceed
      even when medio-lateral positioning is perturbed.

PMID- 29444424
TI  - Activity Regulates Cell Death within Cortical Interneurons through a Calcineurin
      Dependent Mechanism.
AB  - We demonstrate that cortical interneurons derived from ventral eminences,
      including the caudal ganglionic eminence, undergo programmed cell death.
      Moreover, with the exception of VIP interneurons, this occurs in a manner that is
      activity-dependent. In addition, we demonstrate that, within interneurons,
      Calcineurin, a calcium-dependent protein phosphatase, plays a critical role in
      sequentially linking activity to maturation (E15-P5) and survival (P5-P20).
      Specifically, embryonic inactivation of Calcineurin results in a failure of
      interneurons to morphologically mature and prevents them from undergoing
      apoptosis. By contrast, early postnatal inactivation of Calcineurin increases
      apoptosis. We conclude that Calcineurin serves a dual role of promoting first the
      differentiation of interneurons and, subsequently, their survival.

PMID- 29444425
TI  - Modulation of Apoptosis Controls Inhibitory Interneuron Number in the Cortex.
AB  - Cortical networks are composed of excitatory projection neurons and inhibitory
      interneurons. Finding the right balance between the two is important for
      controlling overall cortical excitation and network dynamics. However, it is
      unclear how the correct number of cortical interneurons (CIs) is established in
      the mammalian forebrain. CIs are generated in excess from basal forebrain
      progenitors, and their final numbers are adjusted via an intrinsically determined
      program of apoptosis that takes place during an early postnatal window. Here, we
      provide evidence that the extent of CI apoptosis during this critical period is
      plastic and cell-type specific and can be reduced in a cell-autonomous manner by
      acute increases in neuronal activity. We propose that the physiological state of
      the emerging neural network controls the activity levels of local CIs to modulate
      their numbers in a homeostatic manner.

PMID- 29444426
TI  - Inferior Olive HCN1 Channels Coordinate Synaptic Integration and Complex Spike
      Timing.
AB  - Cerebellar climbing-fiber-mediated complex spikes originate from neurons in the
      inferior olive (IO), are critical for motor coordination, and are central to
      theories of cerebellar learning. Hyperpolarization-activated cyclic-nucleotide
      gated (HCN) channels expressed by IO neurons have been considered as pacemaker
      currents important for oscillatory and resonant dynamics. Here, we demonstrate
      that in vitro, network actions of HCN1 channels enable bidirectional
      glutamatergic synaptic responses, while local actions of HCN1 channels determine
      the timing and waveform of synaptically driven action potentials. These roles are
      distinct from, and may complement, proposed pacemaker functions of HCN channels.
      We find that in behaving animals HCN1 channels reduce variability in the timing
      of cerebellar complex spikes, which serve as a readout of IO spiking. Our results
      suggest that spatially distributed actions of HCN1 channels enable the IO to
      implement network-wide rules for synaptic integration that modulate the timing of
      cerebellar climbing fiber signals.

PMID- 29444427
TI  - An Excitatory Neural Assembly Encodes Short-Term Memory in the Prefrontal Cortex.
AB  - Short-term memory (STM) is crucial for animals to hold information for a small
      period of time. Persistent or recurrent neural activity, together with neural
      oscillations, is known to encode the STM at the cellular level. However, the
      coding mechanisms at the microcircuitry level remain a mystery. Here, we
      performed two-photon imaging on behaving mice to monitor the activity of neuronal
      microcircuitry. We discovered a neuronal subpopulation in the medial prefrontal
      cortex (mPFC) that exhibited emergent properties in a context-dependent manner
      underlying a STM-like behavior paradigm. These neuronal subpopulations
      exclusively comprise excitatory neurons and mainly represent a group of neurons
      with stronger functional connections. Microcircuitry plasticity was maintained
      for minutes and was absent in an animal model of Alzheimer's disease (AD). Thus,
      these results point to a functional coding mechanism that relies on the emergent
      behavior of a functionally defined neuronal assembly to encode STM.

PMID- 29444428
TI  - AgRP Neurons Require Carnitine Acetyltransferase to Regulate Metabolic
      Flexibility and Peripheral Nutrient Partitioning.
AB  - AgRP neurons control peripheral substrate utilization and nutrient partitioning
      during conditions of energy deficit and nutrient replenishment, although the
      molecular mechanism is unknown. We examined whether carnitine acetyltransferase
      (Crat) in AgRP neurons affects peripheral nutrient partitioning. Crat deletion in
      AgRP neurons reduced food intake and feeding behavior and increased glycerol
      supply to the liver during fasting, as a gluconeogenic substrate, which was
      mediated by changes to sympathetic output and peripheral fatty acid metabolism in
      the liver. Crat deletion in AgRP neurons increased peripheral fatty acid
      substrate utilization and attenuated the switch to glucose utilization after
      refeeding, indicating altered nutrient partitioning. Proteomic analysis in AgRP
      neurons shows that Crat regulates protein acetylation and metabolic processing.
      Collectively, our studies highlight that AgRP neurons require Crat to provide the
      metabolic flexibility to optimize nutrient partitioning and regulate peripheral
      substrate utilization, particularly during fasting and refeeding.

PMID- 29444430
TI  - beta Cell-Specific Deletion of the IL-1 Receptor Antagonist Impairs beta Cell
      Proliferation and Insulin Secretion.
AB  - Interleukin-1 receptor antagonist (IL-1Ra) is elevated in the circulation during
      obesity and type 2 diabetes (T2D) but is decreased in islets from patients with
      T2D. The protective role of local IL-1Ra was investigated in pancreatic islet
      beta cell (betaIL-1Ra)-specific versus myeloid-cell (myeloIL-1Ra)-specific IL-1Ra
      knockout (KO) mice. Deletion of IL-1Ra in beta cells, but not in myeloid cells,
      resulted in diminished islet IL-1Ra expression. Myeloid cells were not the main
      source of circulating IL-1Ra in obesity. betaIL-1Ra KO mice had impaired insulin
      secretion, reduced beta cell proliferation, and decreased expression of islet
      proliferation genes, along with impaired glucose tolerance. The key cell-cycle
      regulator E2F1 partly reversed IL-1beta-mediated inhibition of potassium channel
      Kir6.2 expression and rescued impaired insulin secretion in IL-1Ra knockout
      islets. Our findings provide evidence for the importance of beta cell-derived IL
      1Ra for the local defense of beta cells to maintain normal function and
      proliferation.

PMID- 29444429
TI  - Glucagon Receptor Antagonism Improves Glucose Metabolism and Cardiac Function by
      Promoting AMP-Mediated Protein Kinase in Diabetic Mice.
AB  - The antidiabetic potential of glucagon receptor antagonism presents an
      opportunity for use in an insulin-centric clinical environment. To investigate
      the metabolic effects of glucagon receptor antagonism in type 2 diabetes, we
      treated Leprdb/db and Lepob/ob mice with REMD 2.59, a human monoclonal antibody
      and competitive antagonist of the glucagon receptor. As expected, REMD 2.59
      suppresses hepatic glucose production and improves glycemia. Surprisingly, it
      also enhances insulin action in both liver and skeletal muscle, coinciding with
      an increase in AMP-activated protein kinase (AMPK)-mediated lipid oxidation.
      Furthermore, weekly REMD 2.59 treatment over a period of months protects against
      diabetic cardiomyopathy. These functional improvements are not derived simply
      from correcting the systemic milieu; nondiabetic mice with cardiac-specific
      overexpression of lipoprotein lipase also show improvements in contractile
      function after REMD 2.59 treatment. These observations suggest that
      hyperglucagonemia enables lipotoxic conditions, allowing the development of
      insulin resistance and cardiac dysfunction during disease progression.

PMID- 29444431
TI  - Mechanisms to Evade the Phagocyte Respiratory Burst Arose by Convergent Evolution
      in Typhoidal Salmonella Serovars.
AB  - Typhoid fever caused by Salmonella enterica serovar (S.) Typhi differs in its
      clinical presentation from gastroenteritis caused by S. Typhimurium and other non
      typhoidal Salmonella serovars. The different clinical presentations are
      attributed in part to the virulence-associated capsular polysaccharide (Vi
      antigen) of S. Typhi, which prevents phagocytes from triggering a respiratory
      burst by preventing antibody-mediated complement activation. Paradoxically, the
      Vi antigen is absent from S. Paratyphi A, which causes a disease that is
      indistinguishable from typhoid fever. Here, we show that evasion of the phagocyte
      respiratory burst by S. Paratyphi A required very long O antigen chains
      containing the O2 antigen to inhibit antibody binding. We conclude that the
      ability to avoid the phagocyte respiratory burst is a property distinguishing
      typhoidal from non-typhoidal Salmonella serovars that was acquired by S. Typhi
      and S. Paratyphi A independently through convergent evolution.

PMID- 29444432
TI  - Surface-Matrix Screening Identifies Semi-specific Interactions that Improve
      Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody.
AB  - Highly effective HIV-1-neutralizing antibodies could have utility in the
      prevention or treatment of HIV-1 infection. To improve the potency of 10E8, an
      antibody capable of near pan-HIV-1 neutralization, we engineered 10E8-surface
      mutants and screened for improved neutralization. Variants with the largest
      functional enhancements involved the addition of hydrophobic or positively
      charged residues, which were positioned to interact with viral membrane lipids or
      viral glycan-sialic acids, respectively. In both cases, the site of improvement
      was spatially separated from the region of antibody mediating molecular contact
      with the protein component of the antigen, thereby improving peripheral semi
      specific interactions while maintaining unmodified dominant contacts responsible
      for broad recognition. The optimized 10E8 antibody, with mutations to
      phenylalanine and arginine, retained the extraordinary breadth of 10E8 but with
      ~10-fold increased potency. We propose surface-matrix screening as a general
      method to improve antibodies, with improved semi-specific interactions between
      antibody and antigen enabling increased potency without compromising breadth.

PMID- 29444433
TI  - MicroRNA-223 Suppresses the Canonical NF-kappaB Pathway in Basal Keratinocytes to
      Dampen Neutrophilic Inflammation.
AB  - MicroRNA-223 is known as a myeloid-enriched anti-inflammatory microRNA that is
      dysregulated in numerous inflammatory conditions. Here, we report that
      neutrophilic inflammation (wound response) is augmented in miR-223-deficient
      zebrafish, due primarily to elevated activation of the canonical nuclear factor
      kappaB (NF-kappaB) pathway. NF-kappaB over-activation is restricted to the basal
      layer of the surface epithelium, although miR-223 is detected throughout the
      epithelium and in phagocytes. Not only phagocytes but also epithelial cells are
      involved in miR-223-mediated regulation of neutrophils' wound response and NF
      kappaB activation. Cul1a/b, Traf6, and Tab1 are identified as direct targets of
      miR-223, and their levels rise in injured epithelium lacking miR-223. In
      addition, miR-223 is expressed in cultured human bronchial epithelial cells,
      where it also downregulates NF-kappaB signaling. Together, this direct connection
      between miR-223 and the canonical NF-kappaB pathway provides a mechanistic
      understanding of the multifaceted role of miR-223 and highlights the relevance of
      epithelial cells in dampening neutrophil activation.

PMID- 29444434
TI  - B1 Cell IgE Impedes Mast Cell-Mediated Enhancement of Parasite Expulsion through
      B2 IgE Blockade.
AB  - Helminth infection is known for generating large amounts of poly-specific IgE.
      Here we demonstrate that innate-like B1 cells are responsible for this IgE
      production during infection with the nematode parasites Nippostrongylus
      brasiliensis and Heligmosomoides polygyrus bakeri. In vitro analysis of B1 cell
      immunoglobulin class switch recombination to IgE demonstrated a requirement for
      anti-CD40 and IL-4 that was further enhanced when IL-5 was added or when the B1
      source was helminth infected mice. An IL-25-induced upregulation of IgE in B1
      cells was also demonstrated. In T cell-reconstituted RAG1-/- mice, N.
      brasiliensis clearance was enhanced with the addition of B2 cells in an IgE
      dependent manner. This enhanced clearance was impeded by reconstitution with IgE
      sufficient B1 cells. Mucosal mast cells mediated the B2 cell enhancement of
      clearance in the absence of B1 cells. The data support B1 cell IgE secretion as a
      regulatory response exploited by the helminth.

PMID- 29444435
TI  - PTPN2 Regulates Inflammasome Activation and Controls Onset of Intestinal
      Inflammation and Colon Cancer.
AB  - Variants in the gene locus encoding protein tyrosine phosphatase non-receptor
      type 2 (PTPN2) are associated with inflammatory disorders, including inflammatory
      bowel diseases, rheumatoid arthritis, and type 1 diabetes. The anti-inflammatory
      role of PTPN2 is highlighted by the fact that PTPN2-deficient mice die a few
      weeks after birth because of systemic inflammation and severe colitis. However,
      the tissues, cells, and molecular mechanisms that contribute to this phenotype
      remain unclear. Here, we demonstrate that myeloid cell-specific deletion of PTPN2
      in mice (PTPN2-LysMCre) promotes intestinal inflammation but protects from
      colitis-associated tumor formation in an IL-1beta-dependent manner. Elevated
      levels of mature IL-1beta production in PTPN2-LysMCre mice are a consequence of
      increased inflammasome assembly due to elevated phosphorylation of the
      inflammasome adaptor molecule ASC. Thus, we have identified a dual role for
      myeloid PTPN2 in directly regulating inflammasome activation and IL-1beta
      production to suppress pro-inflammatory responses during colitis but promote
      intestinal tumor development.

PMID- 29444437
TI  - Mutations in Cytosine-5 tRNA Methyltransferases Impact Mobile Element Expression
      and Genome Stability at Specific DNA Repeats.
AB  - The maintenance of eukaryotic genome stability is ensured by the interplay of
      transcriptional as well as post-transcriptional mechanisms that control
      recombination of repeat regions and the expression and mobility of transposable
      elements. We report here that mutations in two (cytosine-5) RNA
      methyltransferases, Dnmt2 and NSun2, impact the accumulation of mobile element
      derived sequences and DNA repeat integrity in Drosophila. Loss of Dnmt2 function
      caused moderate effects under standard conditions, while heat shock exacerbated
      these effects. In contrast, NSun2 function affected mobile element expression and
      genome integrity in a heat shock-independent fashion. Reduced tRNA stability in
      both RCMT mutants indicated that tRNA-dependent processes affected mobile element
      expression and DNA repeat stability. Importantly, further experiments indicated
      that complex formation with RNA could also contribute to the impact of RCMT
      function on gene expression control. These results thus uncover a link between
      tRNA modification enzymes, the expression of repeat DNA, and genomic integrity.

PMID- 29444436
TI  - Shwachman-Diamond Syndrome Protein SBDS Maintains Human Telomeres by Regulating
      Telomerase Recruitment.
AB  - Shwachman-Diamond syndrome (SDS) is a rare pediatric disease characterized by
      various systemic disorders, including hematopoietic dysfunction. The mutation of
      Shwachman-Bodian-Diamond syndrome (SBDS) gene has been proposed to be a major
      causative reason for SDS. Although SBDS patients were reported to have shorter
      telomere length in granulocytes, the underlying mechanism is still unclear. Here
      we provide data to elucidate the role of SBDS in telomere protection. We
      demonstrate that SBDS deficiency leads to telomere shortening. We found that
      overexpression of disease-associated SBDS mutants or knockdown of SBDS hampered
      the recruitment of telomerase onto telomeres, while the overall reverse
      transcriptase activity of telomerase remained unaffected. Moreover, we show that
      SBDS could specifically bind to TPP1 during the S phase of cell cycle, likely
      functioning as a stabilizer for TPP1-telomerase interaction. Our findings suggest
      that SBDS is a telomere-protecting protein that participates in regulating
      telomerase recruitment.

PMID- 29444438
TI  - Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by
      Single-Cell Mass Cytometry.
AB  - We have performed an in-depth single-cell phenotypic characterization of high
      grade serous ovarian cancer (HGSOC) by multiparametric mass cytometry (CyTOF).
      Using a CyTOF antibody panel to interrogate features of HGSOC biology, combined
      with unsupervised computational analysis, we identified noteworthy cell types co
      occurring across the tumors. In addition to a dominant cell subset, each tumor
      harbored rarer cell phenotypes. One such group co-expressed E-cadherin and
      vimentin (EV), suggesting their potential role in epithelial mesenchymal
      transition, which was substantiated by pairwise correlation analyses.
      Furthermore, tumors from patients with poorer outcome had an increased frequency
      of another rare cell type that co-expressed vimentin, HE4, and cMyc. These poorer
      outcome tumors also populated more cell phenotypes, as quantified by Simpson's
      diversity index. Thus, despite the recognized genomic complexity of the disease,
      the specific cell phenotypes uncovered here offer a focus for therapeutic
      intervention and disease monitoring.

PMID- 29444439
TI  - Differential Effector Engagement by Oncogenic KRAS.
AB  - KRAS can bind numerous effector proteins, which activate different downstream
      signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase,
      and RalGDS families, but many additional direct and indirect effectors have been
      reported. We have assessed how these effectors contribute to several major
      phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in
      which we knocked down 41 KRAS effectors nodes in 92 cell lines. We show that
      every cell line has a unique combination of effector dependencies, but in spite
      of this heterogeneity, we were able to identify two major subtypes of KRAS mutant
      cancers of the lung, pancreas, and large intestine, which reflect different KRAS
      effector engagement and opportunities for therapeutic intervention.

PMID- 29444440
TI  - Measuring Integrin Conformational Change on the Cell Surface with Super
      Resolution Microscopy.
AB  - We use super-resolution interferometric photoactivation and localization
      microscopy (iPALM) and a constrained photoactivatable fluorescent protein
      integrin fusion to measure the displacement of the head of integrin lymphocyte
      function-associated 1 (LFA-1) resulting from integrin conformational change on
      the cell surface. We demonstrate that the distance of the LFA-1 head increases
      substantially between basal and ligand-engaged conformations, which can only be
      explained at the molecular level by integrin extension. We further demonstrate
      that one class of integrin antagonist maintains the bent conformation, while
      another antagonist class induces extension. Our molecular scale measurements on
      cell-surface LFA-1 are in excellent agreement with distances derived from
      crystallographic and electron microscopy structures of bent and extended
      integrins. Our distance measurements are also in excellent agreement with a
      previous model of LFA-1 bound to ICAM-1 derived from the orientation of LFA-1 on
      the cell surface measured using fluorescence polarization microscopy.

PMID- 29444441
TI  - Initiating Events in Direct Cardiomyocyte Reprogramming.
AB  - Direct reprogramming of fibroblasts into cardiomyocyte-like cells (iCM) holds
      great potential for heart regeneration and disease modeling and may lead to
      future therapeutic applications. Currently, application of this technology is
      limited by our lack of understanding of the molecular mechanisms that drive
      direct iCM reprogramming. Using a quantitative mass spectrometry-based proteomic
      approach, we identified the temporal global changes in protein abundance that
      occur during initial phases of iCM reprogramming. Collectively, our results show
      systematic and temporally distinct alterations in levels of specific functional
      classes of proteins during the initiating steps of reprogramming including
      extracellular matrix proteins, translation factors, and chromatin-binding
      proteins. We have constructed protein relational networks associated with the
      initial transition of a fibroblast into an iCM. These findings demonstrate the
      presence of an orchestrated series of temporal steps associated with dynamic
      changes in protein abundance in a defined group of protein pathways during the
      initiating events of direct reprogramming.

PMID- 29444443
TI  - Kinetics and Mechanism of Mammalian Mitochondrial Ribosome Assembly.
AB  - Mammalian mtDNA encodes only 13 proteins, all essential components of respiratory
      complexes, synthesized by mitochondrial ribosomes. Mitoribosomes contain greatly
      truncated RNAs transcribed from mtDNA, including a structural tRNA in place of 5S
      RNA as a scaffold for binding 82 nucleus-encoded proteins, mitoribosomal proteins
      (MRPs). Cryoelectron microscopy (cryo-EM) studies have determined the structure
      of the mitoribosome, but its mechanism of assembly is unknown. Our SILAC pulse
      labeling experiments determine the rates of mitochondrial import of MRPs and
      their assembly into intact mitoribosomes, providing a basis for distinguishing
      MRPs that bind at early and late stages in mitoribosome assembly to generate a
      working model for mitoribosome assembly. Mitoribosome assembly is a slow process
      initiated at the mtDNA nucleoid driven by excess synthesis of individual MRPs.
      MRPs that are tightly associated in the structure frequently join the complex in
      a coordinated manner. Clinically significant MRP mutations reported to date
      affect proteins that bind early on during assembly.

PMID- 29444442
TI  - Diverse Regulators of Human Ribosome Biogenesis Discovered by Changes in
      Nucleolar Number.
AB  - Ribosome biogenesis is a highly regulated, essential cellular process. Although
      studies in yeast have established some of the biological principles of ribosome
      biogenesis, many of the intricacies of its regulation in higher eukaryotes remain
      unknown. To understand how ribosome biogenesis is globally integrated in human
      cells, we conducted a genome-wide siRNA screen for regulators of nucleolar
      number. We found 139 proteins whose depletion changed the number of nucleoli per
      nucleus from 2-3 to only 1 in human MCF10A cells. Follow-up analyses on 20 hits
      found many (90%) to be essential for the nucleolar functions of rDNA
      transcription (7), pre-ribosomal RNA (pre-rRNA) processing (16), and/or global
      protein synthesis (14). This genome-wide analysis exploits the relationship
      between nucleolar number and function to discover diverse cellular pathways that
      regulate the making of ribosomes and paves the way for further exploration of the
      links between ribosome biogenesis and human disease.

PMID- 29444444
TI  - Vertical disconjugacy during reading in dyslexic and non-dyslexic children.
AB  - PURPOSE: The objective of this study was to explore vertical binocular
      coordination in dyslexic and non-dyslexic children during saccades and post
      saccadic fixation period while reading a text. METHODS: Binocular eye movements
      were recorded by an infrared system (Mobile T2(r), SuriCog) in thirty-six
      dyslexic children from 7.3 to 13.6 years of age (mean age: 10.4 +/- 0.3 years)
      who were asked to silently read a four-line text during binocular viewing. Data
      were compared to those of thirty-six age-matched non-dyslexic children. RESULTS:
      Vertical disconjugacy during post-saccadic fixation was higher in dyslexic
      children with respect to non-dyslexic children group. Vertical disconjugacy was
      not age-dependent either for dyslexic children or for non-dyslexic children.
      CONCLUSIONS: The poor binocular vertical coordination observed in dyslexic
      children while reading could suggest a deficiency in the cerebellum and/or extra
      ocular muscles involved in vertical eye alignment. Moreover, the fact that this
      vertical binocular coordination was not age-dependent could be due to an abnormal
      eye position and/or to a dysfunction of midbrain structures involved in vertical
      vergences.

PMID- 29444445
TI  - Individual differences in the processing of referential dependencies: Evidence
      from event-related potentials.
AB  - The present study examines the processing of referential ambiguity and
      referential failure using event-related potentials (ERPs). Participants read
      sentences with pronouns (he, she) which contained either one, two, or no
      potential gender-matching antecedents. Participants also took tests of working
      memory (Count Span/Reading Span) and attentional control (Number Stroop). In
      contexts of referential ambiguity with two potential gender-matching antecedents,
      two different responder types emerged, with some participants yielding a
      sustained negativity (Nref) and others a sustained positivity. For individuals
      who elicited Nref, the size of the effect was related to working memory such that
      higher Count Span scores were related to a larger Nref. For individuals who
      elicited a positivity, the effect was marginally related to attentional control
      such that better performance on the Stroop was related to a less positive, or
      increasingly negative-going ERP effect. Contexts of referential failure, with no
      gender-matching antecedents, yielded P600 for all participants, suggesting that
      participants may treat the failure of the pronoun to agree in gender with the
      antecedents as a violation despite the absence of an explicit acceptability
      judgment task.

PMID- 29444446
TI  - Pathophysiological changes after lipopolysaccharide-induced acute inflammation in
      a type 2 diabetic rat model versus normal controls.
AB  - AIMS: The present study aimed to explore the mechanism of a potential beneficial
      effect of pre-existing diabetes in acute hyperglycemia during critical illness.
      METHODS: Pathophysiological changes including blood glucose variability, changes
      of inflammatory and oxidative stress responses after lipopolysaccharide (LPS)
      induced acute infection were compared between type 2 diabetic rat model (GK rats)
      and normal controls (Wistar rats). RESULTS: After LPS injection, Wistar rats
      showed serious infective symptoms while GK rats did not. Blood glucose (BG)
      levels were significantly elevated in both GK and Wistar rats; however, compared
      to Wistar rats, GK rats had lower BG variability, smaller increases in the serum
      tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels, a larger
      increase in the serum IL-10 level, and a smaller decrease in the IkappaB-alpha
      protein level of lung tissue. Serum malondialdehyde (MDA) levels increased and
      serum total antioxidant capacity (T-AOC) levels decreased for both GK and Wistar
      rats. CONCLUSIONS: We found diabetes was associated with adaptive changes at the
      cellular level that might actually be protective in acute hyperglycemia-mediated
      damage during sepsis. Chronic exposure to hyperglycemia potentially reduced the
      acute deleterious effects of acute hyperglycemia on septic mortality by
      decreasing BG variability, blunting the pro-inflammatory response and elevating
      the anti-inflammatory response.

PMID- 29444448
TI  - Tracking small sensory nerve action potentials in human axonal excitability
      studies.
AB  - BACKGROUND: Excitability studies on normal and diseased human axons in vivo have
      been greatly enhanced by fast non-invasive threshold-tracking techniques, using
      surface stimulation and recording. Although sensory axons are often more affected
      in disease, most studies to date have focussed on motor axons, because of
      technical difficulties in resolving pathologically small nerve volleys in the
      presence of noise and stimulus artefact. NEW METHODS: This paper describes
      techniques for tracking low-amplitude compound action potentials, using a battery
      powered, isolated preamplifier of simple construction with high common mode
      rejection (>125 dB [balanced inputs]) and low noise (<0.4 MUV referred to inputs
      [shorted]). RESULTS: We demonstrate the preamplifier's capability by tracking
      targets as small as 2 MUV for a full range of excitability measurements without
      the usual distortion due to residual stimulus artefact and without the need for
      clamping, additional filtering or ensemble averaging. COMPARISON WITH EXISTING
      METHODS: In practice, threshold-tracking studies have been unable to study
      sensory axons when the maximal compound sensory action potential was less than
      about 15 MUV. The techniques and amplifier in the present study allow
      measurements to be made from nerve with maximal responses less than half that
      size, and we present three recordings in patients with pathologically small nerve
      action potentials <=7 MUV. CONCLUSIONS: Based on measurements of stimulus
      artefact distortion, noise and the performance in experiments, we conclude that
      the techniques described here will facilitate the study of diseased axons for
      which the sensory potentials have high thresholds and may be only a few
      microvolts in amplitude.

PMID- 29444447
TI  - Difference between observed and predicted glycated hemoglobin at baseline and
      treatment response to vildagliptin-based dual oral therapy in patients with type
      2 diabetes.
AB  - AIM: We aimed to investigate the association of difference between observed and
      predicted glycated hemoglobin (dopHbA1c) and HbA1c reduction after vildagliptin
      based oral therapy in patients with type 2 diabetes (T2D). METHODS: This was a
      prospective observational study. Adults >= 20 years old with T2D and HbA1c ?7%
      treated with oral anti-diabetic drugs (OADs) were eligible if their OADs were
      shifted to vildagliptin-based dual oral therapy. Fasting plasma glucose (FPG) and
      HbA1c were recorded at baseline, week 12, and week 24. To determine baseline
      dopHbA1c, a predicted HbA1c was calculated by inserting baseline FPG into a
      regression equation (HbA1c = FPG * 0.0225 + 4.3806) developed from linear
      relationship between HbA1c and FPG in an independent cohort of 3239 outpatients
      with T2D (dopHbA1c = observed HbA1c - predicted HbA1c). Patients were assigned to
      low (?0) or high (>0) dopHbA1c group according to their baseline dopHbA1c levels.
      The study endpoint was changes from baseline to week 24 in HbA1c levels. RESULTS:
      A total of 1224 patients were enrolled. Patients with a dopHbA1c >0 had a greater
      HbA1c reduction after vildagliptin-based dual oral therapy than those with a
      dopHbA1c ?0 (-1.5 +/- 2.0 vs. -0.4 +/- 1.0%, p < 0.001). Baseline dopHbA1c was
      positively associated with HbA1c reduction from baseline to week 24 (beta
      coefficient 0.883, 95% CI 0.811 to 0.955, p < 0.001), and the association
      remained significant after adjustment for confounders. CONCLUSIONS: In T2D
      patients with an HbA1c ?7%, a higher baseline dopHbA1c was associated with a
      greater HbA1c reduction after shifting to vildagliptin-based dual oral therapy.

PMID- 29444449
TI  - Dendritic spine density and EphrinB2 levels of hippocampal and anterior cingulate
      cortex neurons increase sequentially during formation of recent and remote fear
      memory in the mouse.
AB  - Memory consolidation is a dynamic process that involves a sequential remodeling
      of hippocampal-cortical circuits. Although synaptic events underlying memory
      consolidation are well assessed, fine molecular events controlling this process
      deserve further characterization. To this aim, we challenged male C57BL/6N mice
      in a contextual fear conditioning (CFC) paradigm and tested their memory 24 h, 7
      days or 36 days later. Mice displayed a strong fear response at all time points
      with an increase in dendritic spine density and protein levels of the cell
      adhesion factor EphrinB2 in CA1 hippocampal neurons 24 h and 7 days post
      conditioning (p.c.), and in anterior cingulate cortex (ACC) neurons 36 days p.c.
      We then investigated whether the formation of remote memory and neuronal
      modifications in the ACC would depend on p.c. protein synthesis in hippocampal
      neurons. Bilateral intrahippocampal infusions with the protein synthesis
      inhibitor anisomycin administered immediately p.c. decreased fear response,
      neuronal spine growth and EphrinB2 protein levels of hippocampal and ACC neurons
      24 h and 36 days p.c., respectively. Anisomycin infusion 24 h p.c. had no effects
      on fear response, increase in spine density and in EphrinB2 protein levels in ACC
      neurons 36 days p.c. Our results thus confirm that early but not late p.c.
      hippocampal protein synthesis is necessary for the formation of remote memory and
      provide the first evidence of a possible involvement of EphrinB2 in neuronal
      plasticity in the ACC.

PMID- 29444451
TI  - Risk factors for neonatal death in the capital city with the lowest infant
      mortality rate in Brazil.
AB  - OBJECTIVES: To analyze the risk factors for neonatal death in Florianopolis, the
      Brazilian city capital with the lowest infant mortality rate. METHOD: Data were
      extracted from a historical cohort with 15,879 live births. A model was used that
      included socioeconomic, behavioral, and health service use risk factors, as well
      as the Apgar score and biological factors. Risk factors were analyzed by
      hierarchical logistic regression. RESULTS: Based on the multivariate analysis,
      socioeconomic factors showed no association with death. Insufficient prenatal
      consultations showed an OR of 3.25 (95% CI: 1.70-6.48) for death. Low birth
      weight (OR 8.42; 95% CI: 3.45-21.93); prematurity (OR 5.40; 95% CI: 2.22-13.88);
      malformations (OR 4.42; 95% CI: 1.37-12.43); and low Apgar score at the first (OR
      6.65; 95% CI: 3.36-12.94) and at the fifth (OR 19.78; 95% CI: 9.12-44.50)
      minutes, were associated with death. CONCLUSION: Differing from other studies,
      socioeconomic conditions were not associated with neonatal death. Insufficient
      prenatal consultations, low Apgar score, prematurity, low birth weight, and
      malformations showed an association, reinforcing the importance of prenatal
      access universalization and its integration with medium and high-complexity
      neonatal care services.

PMID- 29444450
TI  - High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS
      complex and perturb RAS signaling.
AB  - K-RAS is mutated in approximately 30% of human cancers, resulting in increased
      RAS signaling and tumor growth. Thus, RAS is a highly validated therapeutic
      target, especially in tumors of the pancreas, lung and colon. Although directly
      targeting RAS has proven to be challenging, it may be possible to target other
      proteins involved in RAS signaling, such as the guanine nucleotide exchange
      factor Son of Sevenless (SOS). We have previously reported on the discovery of
      small molecules that bind to SOS1, activate SOS-mediated nucleotide exchange on
      RAS, and paradoxically inhibit ERK phosphorylation (Burns et al., PNAS, 2014).
      Here, we describe the discovery of additional, structurally diverse small
      molecules that also bind to SOS1 in the same pocket and elicit similar biological
      effects. We tested >160,000 compounds in a fluorescence-based assay to assess
      their effects on SOS-mediated nucleotide exchange. X-Ray structures revealed that
      these small molecules bind to the CDC25 domain of SOS1. Compounds that elicited
      high levels of nucleotide exchange activity in vitro increased RAS-GTP levels in
      cells, and inhibited phospho ERK levels at higher treatment concentrations. The
      identification of structurally diverse SOS1 binding ligands may assist in the
      discovery of new molecules designed to target RAS-driven tumors.

PMID- 29444452
TI  - Insulation fiber deposition in the airways of men and rats. A review of
      experimental and computational studies.
AB  - The typical insulation rock, slag and glass wool fibers are high volume
      materials. Current exposure levels in industry (generally <= 1 fiber/cm3 with a
      median diameter ~1 MUm and length >=10 MUm) are not considered carcinogenic or
      causing other types of severe lung effects. However, epidemiological studies are
      not informative on effects in humans at fiber levels >1 fiber/cm3. Effects may be
      inferred from valid rat studies, conducted with rat respirable fibers (diameter
      <= 1.5 MUm). Therefore, we estimate delivery and deposition in human and rat
      airways of the industrial fibers. The deposition fractions in humans head regions
      by nasal (~0.20) and by mouth breathing (<=0.08) are lower than in rats (0.50).
      The delivered dose into the lungs per unit lung surface area during a 1-day
      exposure at a similar air concentration is estimated to be about two times higher
      in humans than in rats. The deposition fractions in human lungs by nasal (~0.20)
      and by mouth breathing (~0.40) are higher than in rats (~0.04). The human lung
      deposition may be up to three times by nasal breathing and up to six times higher
      by oral breathing than in rats, qualifying assessment factor setting for
      deposition.

PMID- 29444453
TI  - Efferocytosis in atherosclerotic lesions: Malfunctioning regulatory pathways and
      control mechanisms.
AB  - Atherosclerosis is a dynamic and progressive inflammatory process in the intimal
      layer of large and medium-sized arteries, and it is the major contributor to the
      atherosclerotic cardiovascular disease (ACVD), the leading cause of death
      worldwide. In an atherosclerotic plaque, phagocytosis of apoptotic cells occurs
      through an intricate process designated efferocytosis. Defective efferocytosis
      has emerged as a causal factor in the etiopathogenesis of atherosclerosis and its
      progression into overt ACVD. Both specialized phagocytes (macrophages and
      dendritic cells) and non-specialized cells with phagocytic capabilities (smooth
      muscle and endothelial cells) are involved in the efferocytotic process.
      Moreover, several signaling and regulatory molecules are involved in the
      different steps of efferocytosis, and they include "Find-Me" signals
      (lysophosphatidylcholine), "Eat-Me" signals [phosphatidylserine, Mer tyrosine
      kinase (MerTK), and milk fat globule-EGF factor 8], and "Don't Eat-Me" signals
      [cluster of differentiation 47 (CD47)]. Regulation of efferocytosis is in a close
      nexus with inflammation, the key component in atherosclerosis. The predominance
      of pro-inflammatory and anti-inflammatory molecules plays a crucial role in
      lesion progression and regression, respectively. Polarization of macrophages
      towards the M1 phenotype causes them to secrete proinflammatory cytokines, while
      polarization towards the M2 phenotype causes them to secrete of anti-inflammatory
      cytokines, including interleukin-10 and transforming growth factor beta, so
      tending to shift the balance towards resolution of the inflammation. Dysfunction
      of any regulatory signal may cause expansion of the necrotic core of an
      atherosclerotic plaque with ensuing conversion of the plaque into an unstable
      plaque with an increased susceptibility to rupture and to atherothrombotic
      complication. In this review we aim at elucidating the determinant factors and
      pathways of efferocytosis which can be considered as potential novel targets when
      striving to develop more personalized and efficient treatment regimens for
      patients with ACVD.

PMID- 29444454
TI  - Assessing the blocking of occasion setting.
AB  - An occasion setter (OS) is a stimulus or context with the capacity to
      disambiguate an ambiguous conditioned stimulus (CS). Previous research has shown
      that OSs share some features with regular Pavlovian CSs. Amongst them, research
      has shown that OSs are subject to blocking; that is, a new OS exerts reduced
      behavioral control after training in compound with a previously established OS.
      Of additional interest, in Pavlovian blocking, it has been reported that a
      blocked CS comes to elicit conditioned responding after the extinction of the
      blocking CS. This is an example of retrospective revaluation, a family of
      phenomena in which the response to a specific stimulus is modified by training a
      related cue. Here, three experiments sought to extend the analogies between OS
      and Pavlovian conditioning by examining the blocking of OSs and its retrospective
      revaluation. In all experiments, an OS was established by pairing a CS with food
      in the presence of the OS, but not in its absence (i.e., positive OS). Blocking
      was then trained by presenting the OS in compound with a novel OS. Experiment 1
      showed blocking of the second OS, but direct exposure to the blocking OS did not
      enhance responding to the second OS. Experiment 2 replicated the blocking effect
      but subsequent training of the blocking OS with a reversed contingency showed no
      retrospective revaluation. Experiment 3 examined whether blocking of the OS
      occurred with a novel CS during the compound phase. In this experiment blocking
      was again observed, but only when subjects were tested with the original CS.
      These results are discussed focusing on the underlying links at work in occasion
      setting.

PMID- 29444455
TI  - The perceptions of anatomists in the US and Europe of the skills and attributes
      required of newly-recruited medical students.
AB  - BACKGROUND AND PURPOSE: Admission procedures for recruiting students to medical
      school vary considerably across the world. Notwithstanding such variability, it
      is important to know what skills and attributes (including attitudes and
      personality traits) are required of the students by their teachers on entering
      medical school. PROCEDURES: Anatomists are often the teachers who first meet the
      students as they enter medical school and this report analyses, by means of a
      paper-based questionnaire, the putative skills required of their medical students
      by anatomists from the U.S.A. and Europe. Questionnaires were distributed to 150
      anatomists, of varying ages and teaching experience, with 108 responding with
      completed questionnaires (i.e. 72% returns). FINDINGS: The findings from a
      questionnaire suggest that there are few differences between anatomists in the
      U.S.A. and Europe, even though medical students are postgraduates in the U.S.A.
      but undergraduates in Europe. Furthermore, the skill requirements expected of the
      students differed only slightly according to the gender and age of the anatomists
      and to whether or not they had clinical qualifications. In order of perceived
      importance, the most important skills and attributes required of the students
      were found to be: good study skills, memory/factual retention, conscientiousness,
      emotional stability, understanding of biology (but not chemistry, physics,
      mathematics, statistics, or understanding of the scientific method), life-long
      learning skills, ability to study independently, problem-solving abilities,
      readiness to be challenged, communication skills, and teamwork skills.
      CONCLUSIONS: Anatomists within the U.S.A. and Europe essentially agree on the
      skills and attributes initially required of their medical students, as well as
      those not deemed initially important. These findings are presented with the view
      of enhancing admission policies and procedures for admitting students into
      medical schools.

PMID- 29444456
TI  - Gap junctional intercellular communication and endoplasmic reticulum stress
      regulate chronic cadmium exposure induced apoptosis in HK-2 cells.
AB  - Cadmium (Cd), a toxic heavy metal, is known to induce renal toxicity by primarily
      targeting at renal proximal tubule. Endoplasmic reticulum (ER) stress and gap
      junctional intercellular communication (GJIC) regulate many pathophysiological
      processes. Yet, how ER stress and GJIC regulate Cd-induced nephrotoxicity remain
      elusive. In this study, we treated human proximal tubule (HK-2) cells with 1 MUM
      CdCl2 every other day for 12 days and found that Cd significantly increased cell
      apoptosis at 10 and 12 days. This cytotoxicity correlated with activation of ER
      stress and apoptotic signaling evidenced by upregulation of inositol-requiring
      enzyme 1 (IRE1alpha), splice X-box binding protein-1 (XBP-1s), and apoptosis
      signal-regulating kinase 1 (ASK1) proteins. Interestingly, the AKT signaling was
      activated at 2- and 4-day and then inhibited at 10- and 12-day of Cd treatment;
      by contrast, Cd decreased GJIC levels at 2- and 4-day followed by a significant
      increase at 10- and 12-day treatment. Activation of AKT by SC79 or inhibition of
      GJIC by 18alpha-glycyrrhetinic acid (18alpha-GA) completely abolished Cd-induced
      AKT inhibition and IRE1alpha-ASK1 activation. Importantly, pretreatment with ER
      stress inhibitor or 18alpha-GA significantly mitigated Cd-induced apoptosis.
      These results suggest that GJIC collaborates with AKT signaling and ER stress in
      regulating prolonged Cd-treatment-induced apoptosis in HK-2 cells.

PMID- 29444457
TI  - Brain-region specific responses of astrocytes to an in vitro injury and
      neurotrophins.
AB  - Astrocytes are a heterogeneous population of glial cells that react to brain
      insults through a process referred to as astrogliosis. Reactive astrocytes are
      characterized by an increase in proliferation, size, migration to the injured
      zone and release of a plethora of chemical mediators such as NGF and BDNF. The
      aim of this study was to determine whether there are brain region-associated
      responses of astrocytes to an injury and to the neurotrophins NGF and BDNF. We
      used the scratch injury model to study the closure of a wound inflicted on a
      monolayer of astrocytes obtained from cortex, hippocampus or striatum. Our
      results indicate that the response of astrocytes to a mechanical lesion differ
      according to brain regions. Astrocytes from the striatum proliferate and
      repopulate the injury site more rapidly than astrocytes from cortex or
      hippocampus. We found that the scratch injury induced the upregulation of
      neurotrophin receptor p75NTR and TrkB.t in astrocytes from all brain regions
      studied. When astrocytes from all regions were treated with NGF, the neurotrophin
      induced migration of the astrocytes (assessed in Boyden chambers) and induced
      wound closure but did not affect proliferation. In contrast, BDNF induced wound
      closure but only in astrocytes from striatum. Our overall findings show the
      heterogeneity in astrocyte functions based on their brain region of origin, and
      how this functional diversity may determine their responses to an injury and to
      neurotrophins.

PMID- 29444458
TI  - Effect of glycated insulin on the blood-brain barrier permeability: An in vitro
      study.
AB  - Altered blood-brain barrier (BBB) permeability may contribute to pathogenesis of
      diabetes-related central nervous system disorders. Considering the presence of
      glycated insulin in plasma of type 2 diabetic patients, we hypothesized that
      glycated insulin could induce changes in paracellular permeability in BBB.
      Therefore, the authors decided to study the effect of glycated insulin on
      paracellular permeability in a BBB model and the change induced in insulin
      conformation upon glycation. In this study, the structural modification was
      examined by fluorescence and circular dichroism spectroscopies and dynamic light
      scattering. Cell proliferation and production of ROS in astrocytes and HUVEC
      cells were analyzed by MTT and spectrofluorometric assays, respectively.
      Apoptosis induction was determined and confirmed by flow cytometry and western
      blot analyses, respectively. The permeability was measured Lucifer yellow and
      FITC-Dextran. According to our results, glycated insulin presented altered
      conformation and more exposed hydrophobic patches than insulin. Formation of
      oligomeric species and advanced glycated end products (AGEs) were determined.
      Lower cell viability, higher apoptosis, and more ROS were detected upon treatment
      of cells with glycated insulin. Finally, glycated insulin led to increased
      Lucifer yellow and FITC-dextran transportation across the BBB model which could
      result from ROS producing and apoptosis-inducing activities of AGE-insulin.

PMID- 29444459
TI  - Cell adhesion and matricellular support by astrocytes of the tripartite synapse.
AB  - Astrocytes contribute to the formation, function, and plasticity of synapses.
      Their processes enwrap the neuronal components of the tripartite synapse, and due
      to this close interaction they are perfectly positioned to modulate neuronal
      communication. The interaction between astrocytes and synapses is facilitated by
      cell adhesion molecules and matricellular proteins, which have been implicated in
      the formation and functioning of tripartite synapses. The importance of such
      neuron-astrocyte integration at the synapse is underscored by the emerging role
      of astrocyte dysfunction in synaptic pathologies such as autism and
      schizophrenia. Here we review astrocyte-expressed cell adhesion molecules and
      matricellular molecules that play a role in integration of neurons and astrocytes
      within the tripartite synapse.

PMID- 29444460
TI  - Plasmacytoid pre-dendritic cells (pDC): from molecular pathways to function and
      disease association.
AB  - Plasmacytoid pre-dendritic cells (pDC) are a specialized DC population with a
      great potential to produce large amounts of type I interferon (IFN). pDC are
      involved in the initiation of antiviral immune responses through their
      interaction with innate and adaptive immune cell populations. In a context
      dependent manner, pDC activation can induce their differentiation into mature DC
      able to induce both T cell activation or tolerance. In this review, we described
      pDC functions during immune responses and their implication in the clearance or
      pathogenicity of human diseases during infection, autoimmunity, allergy and
      cancer. We discuss recent advances in the field of pDC biology and their
      implication for future studies.

PMID- 29444461
TI  - Homology threading to generate RNA polymerase structures.
AB  - Homology threading is a powerful technology for generating structural models
      based on homologous structures. Here we use threading to generate four complex
      RNA polymerase models. The models appear to be as useful as x-ray crystal
      structures or cryo-electron microscopy structures to support research projects.

PMID- 29444462
TI  - Photodynamic therapy as a new approach to Trichomonas vaginalis inactivation.
AB  - The emergence of nitroimidazole resistant isolates has been an aggravating factor
      in the treatment of trichomoniasis, the most common non-viral sexually
      transmitted disease in the world. This highlights the importance of new
      technologies that are safe, effective, and have minor side effects or resistance.
      Hence, we evaluated the effectiveness of photodynamic therapy on the inactivation
      of Trichomonas vaginalis in vitro. We used methylene blue as a photosensitizing
      substance, and a light-emitting diode (LED) for irradiation of metronidazole
      sensitive and resistant strains. Our results showed that only the presence of
      light did not interfere with parasite growth; however, methylene blue isolated or
      associated with light inhibited 31.78% +/- 7.18 and 80.21% +/- 7.11 of the
      sensitive strain, respectively, and 31.17% +/- 4.23 and 91.13% +/- 2.31 of the
      resistant strain, respectively. The high trichomonicidal activity of the
      photodynamic therapy, associated with low cost and ease of application, signalize
      its great therapeutic potential not only when conventional treatment fails, but
      also routinely in women with trichomoniasis.

PMID- 29444463
TI  - A comparative study on oxidative stress response in the hepatopancreas and midgut
      of the white shrimp Litopenaeus vannamei under gradual changes to low or high pH
      environment.
AB  - White shrimp Litopenaeus vannamei were reared under conditions of gradual changes
      to a low pH (gradual-low pH, 6.65-8.20) or a high pH (gradual-high pH, 8.20-9.81)
      versus a normal pH environment (8.14-8.31) during a 28-day period. Survival of
      shrimp, and ROS production, antioxidant responses and oxidative damage in the
      hepatopancreas and midgut were investigated. Consequently, shrimp enhanced MnSOD,
      GPx, and Hsp70 transcripts as early defense mechanism in the hepatopancreas and
      midgut to scavenge excessive ROS during short-term (<= 7 days) gradual-low and
      high pH stress. Meanwhile, the hepatopancreas was more sensitive to ROS than
      midgut because of earlier ROS production increase, antioxidant response and
      oxidative damage. Then, suppressed antioxidant response in the hepatopancreas and
      midgut of shrimp suggested a loss of antioxidant regulatory capacity caused by
      aggravated oxidative damage after long-term (>= 14 days) gradual-high pH stress,
      leading to continuous death. However, enhanced GPx, GST, and Hsp70 transcripts in
      the hepatopancreas and midgut might be long-term(>= 14 days) antioxidant
      adaptation mechanism of shrimp to gradual-low pH stress, which could prevent
      further ROS perturbation and weaken oxidative damage to achieve a new immune
      homeostasis, contributing to stable survival rate. Therefore, we have a few
      insights that it is necessary to protect hepatopancreas for controlling shrimp
      death under gradual-high pH stress.

PMID- 29444464
TI  - Transcriptional profiling, molecular cloning, and functional analysis of C1
      inhibitor, the main regulator of the complement system in black rockfish,
      Sebastes schlegelii.
AB  - C1-inhibitor (C1inh) plays a crucial role in assuring homeostasis and is the
      central regulator of the complement activation involved in immunity and
      inflammation. A C1-inhibitor gene from Sebastes schlegelii was identified and
      designated as SsC1inh. The identified genomic DNA and cDNA sequences were 6837 bp
      and 2161 bp, respectively. The genomic DNA possessed 11 exons, interrupted by 10
      introns. The amino acid sequence possessed two immunoglobulin-like domains and a
      serpin domain. Multiple sequence alignment revealed that the serpin domain of
      SsC1inh was highly conserved among analyzed species where the two immunoglobulin
      like domains showed divergence. The distinctiveness of teleost C1inh from other
      homologs was indicated by the phylogenetic analysis, genomic DNA organization,
      and their extended N-terminal amino acid sequences. Under normal physiological
      conditions, SsC1inh mRNA was most expressed in the liver, followed by the gills.
      The involvement of SsC1inh in homeostasis was demonstrated by modulated
      transcription profiles in the liver and spleen upon pathogenic stress by
      different immune stimulants. The protease inhibitory potential of recombinant
      SsC1inh (rSsC1inh) and the potentiation effect of heparin on rSsC1inh was
      demonstrated against C1esterase and thrombin. For the first time, the anti
      protease activity of the teleost C1inh against its natural substrates C1r and C1s
      was proved in this study. The protease assay conducted with recombinant black
      rockfish C1r and C1s proteins in the presence or absence of rSsC1inh showed that
      the activities of both proteases were significantly diminished by rSsC1inh. Taken
      together, results from the present study indicate that SsC1inh actively plays a
      significant role in maintaining homeostasis in the immune system of black rock
      fish.

PMID- 29444465
TI  - Simultaneous detection of human CYP2C19 polymorphisms and antibiotic resistance
      of Helicobacter pylori using a personalised diagnosis kit.
AB  - OBJECTIVES: A personalised diagnosis kit for Helicobacter pylori that employs
      visual gene chip technology for the simultaneous detection of CYP2C19
      polymorphisms and clarithromycin/levofloxacin antibiotic resistance was
      evaluated. METHODS: Gastric antrum mucosa biopsy specimens of 394 patients were
      tested using the kit. DNA sequencing and antibiotic susceptibility testing of the
      H. pylori were also performed. RESULTS: In total, 267 (67.8%) of the 394
      specimens were positive for H. pylori using the kit and DNA sequencing, and 136
      (34.5%) were positive by culturing. For human CYP2C19 and the bacterial 23S rRNA
      and gyrA genes, the concordance rates were 92.4% (364/394), 96.6% (258/267) and
      97.0% (259/267) between the kit and DNA sequencing results, respectively. For
      clarithromycin and levofloxacin resistance, the concordance rates were 90.4%
      (123/136) and 81.6% (111/136) between the kit and antibiotic susceptibility
      testing results. CONCLUSIONS: The personalised diagnosis kit for H. pylori
      provides useful information for the choice of proton pump inhibitor and
      antibiotic in combination therapy.

PMID- 29444466
TI  - Interference and problem size effect in multiplication fact solving: Individual
      differences in brain activations and arithmetic performance.
AB  - In the development of math ability, a large variability of performance in solving
      simple arithmetic problems is observed and has not found a compelling explanation
      yet. One robust effect in simple multiplication facts is the problem size effect,
      indicating better performance for small problems compared to large ones.
      Recently, behavioral studies brought to light another effect in multiplication
      facts, the interference effect. That is, high interfering problems (receiving
      more proactive interference from previously learned problems) are more difficult
      to retrieve than low interfering problems (in terms of physical feature overlap,
      namely the digits, De Visscher and Noel, 2014). At the behavioral level, the
      sensitivity to the interference effect is shown to explain individual differences
      in the performance of solving multiplications in children as well as in adults.
      The aim of the present study was to investigate the individual differences in
      multiplication ability in relation to the neural interference effect and the
      neural problem size effect. To that end, we used a paradigm developed by De
      Visscher, Berens, et al. (2015) that contrasts the interference effect and the
      problem size effect in a multiplication verification task, during functional
      magnetic resonance imaging (fMRI) acquisition. Forty-two healthy adults, who
      showed high variability in an arithmetic fluency test, participated in our fMRI
      study. In order to control for the general reasoning level, the IQ was taken into
      account in the individual differences analyses. Our findings revealed a neural
      interference effect linked to individual differences in multiplication in the
      left inferior frontal gyrus, while controlling for the IQ. This interference
      effect in the left inferior frontal gyrus showed a negative relation with
      individual differences in arithmetic fluency, indicating a higher interference
      effect for low performers compared to high performers. This region is suggested
      in the literature to be involved in resolution of proactive interference.
      Besides, no correlation between the neural problem size effect and multiplication
      performance was found. This study supports the idea that the interference due to
      similarities/overlap of physical traits (the digits) is crucial in memorizing
      arithmetic facts and in determining individual differences in arithmetic.

PMID- 29444467
TI  - Olfactory function in systemic lupus erythematosus and systemic sclerosis. A
      longitudinal study and review of the literature.
AB  - BACKGROUND/PURPOSE: To evaluate olfactory function in systemic lupus
      erythematosus (SLE), systemic sclerosis (SSc) and healthy controls over a 2-year
      period, and to determine the association of olfactory dysfunction with age,
      disease activity, disease damage, treatment, anxiety and depression symptoms and
      limbic structures volumes. METHODS: Consecutive SLE and SSc patients were
      enrolled in this study. Clinical, laboratory disease activity and damage were
      assessed according to diseases specific guidelines. Olfactory functions were
      evaluated using the Sniffin' Sticks test (TDI). Volumetric magnetic resonance
      imaging (MRI) was obtained in a 3T Phillips scanner. Amygdalae and hippocampi
      volumes were analyzed using FreeSurfer(r) software. RESULTS: We included 143 SLE,
      57 SSc and 166 healthy volunteers. Olfactory dysfunction was observed in 78
      (54.5%) SLE, 35 (59.3%) SSc patients and in 24 (14.45%) controls (p<0.001) at
      study entry. SLE and SSc patients had significantly lower mean in all three
      phases (TDI) of the olfactory assessment when compared with healthy volunteers.
      In SLE, the presence of olfactory dysfunction was associated with older age,
      disease activity, higher anxiety and depression symptoms score, smaller left
      hippocampus volume, smaller left and right amygdalae volume and the presence of
      anti-ribosomal P (anti-P) antibodies. In SSc the presence of olfactory impairment
      was associated with older age, disease activity, smaller left and right
      hippocampi volumes and smaller right amygdala volume. Olfactory function was
      repeated after a 2-year period in 90 SLE, 35 SSc and 62 controls and was stable
      in all three groups. CONCLUSION: Both SLE and SSc patients with longstanding
      disease had significant reduction in all stages of TDI that maintained stable
      over a 2-year period. Olfactory dysfunction was associated with age, inflammation
      and hippocampi and amygdalae volumes. In SLE, additional association with anti-P,
      anxiety and depression symptoms was observed.

PMID- 29444468
TI  - A major component of vitamin E, alpha-tocopherol inhibits the anti-tumor activity
      of crizotinib against cells transformed by EML4-ALK.
AB  - Crizotinib is an inhibitor of anaplastic lymphoma kinase (ALK) and is of
      significant therapeutic benefit to patients with non-small cell lung cancer
      (NSCLC) harboring the EML4-ALK fusion gene. In the present study, we demonstrated
      that alpha-tocopherol, a major component of vitamin E, attenuated the effects of
      crizotinib independently of its anti-oxidant properties. alpha-Tocopherol
      significantly inhibited crizotinib-induced apoptosis in cells transformed by EML4
      ALK. It also effectively attenuated the crizotinib-induced inhibition of EML4-ALK
      and its downstream molecules, STAT3 and ERK, and suppressed the inhibitory
      effects of crizotinib on EML4-ALK-mediated transformation in the focus formation
      assay. On the other hand, other members of the vitamin E family, namely, beta
      tocopherol, gamma-tocopherol, delta-tocopherol, and alpha-tocotrienol, and a
      water-soluble analog of vitamin E, Trolox had no effects on the anti-tumor
      activity of crizotinib in cells transformed by EML4-ALK. Collectively, these
      results revealed the risk of the anti-tumor activity of crizotinib being
      attenuated when it is administrated in combination with vitamin E supplements
      containing alpha-tocopherol as a major component.

PMID- 29444469
TI  - Mangiferin prevents diabetic nephropathy progression and protects podocyte
      function via autophagy in diabetic rat glomeruli.
AB  - Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes
      mellitus and is a leading cause of end stage renal disease. Numerous studies
      suggest that podocyte injury contributes to progressive proteinuria. Podocytes
      are highly specialized, terminally differentiated cells that are unable to
      proliferate, autophagy plays a key role in maintaining the structure and function
      of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte
      loss, which leads to massive proteinuria in DN. In the present study, we
      investigated the effects of mangiferin on nephropathy in streptozotocin (STZ)
      induced diabetic rats; we focused on pathological factors related to autophagy in
      podocytes and the AMPK-mTOR-ULK1 pathway. The results showed that chronic
      treatment with mangiferin significantly decreased albuminuria, inhibited
      glomerular extracellular matrix expansion and restored the expression of nephrin,
      a podocyte marker, in diabetic rats; these results suggest that mangiferin
      delayed the process of DN and protected the podocytes. In addition, mangiferin
      induced autophagy, as shown by the up-regulation of LC3 II and the down
      regulation of p62 in both DN rats and podocytes. Transmission electron microscope
      analyses showed that mangiferin increased the number of autophagosomes in the
      podocytes of DN rats. This underlying mechanism was associated with the up
      regulation of AMPK phosphorylation, the down-regulation of mTOR phosphorylation
      and the up-regulation of p-ULK1. Taken together, mangiferin delayed the
      progression of DN and protected the podocytes by enhancing autophagy under
      diabetic conditions via the AMPK-mTOR-ULK1 pathway. These findings provide new
      insights into the molecular mechanisms underlying the renoprotective effects of
      mangiferin in DN.

PMID- 29444470
TI  - Effect of sirolimus on liver cirrhosis and hepatic encephalopathy of common bile
      duct-ligated rats.
AB  - Cirrhosis is often associated with portal hypertension and portal-systemic
      collateral vessels formation attributed to angiogenesis, which leads to severe
      complications as hepatic encephalopathy. Sirolimus has anti-fibrosis and anti
      angiogenesis effects, but whether it influences the severity of portal-systemic
      collaterals and hepatic encephalopathy is unknown. This study was thus designed
      to address this issue in rats with common bile duct ligation-induced liver
      cirrhosis. Sham-operated rats were surgical controls. Rats were intraperitoneally
      administered with 0.5 and 2 mg/kg/day sirolimus or vehicle for 2 weeks. Four
      weeks post operations, motor activities, body weight, biochemistry and
      hemodynamic data were measured. The liver was dissected for histopathology,
      immunohistochemical stains and protein analysis. On the parallel cirrhotic
      groups, the portal-systemic shunting was determined. The results showed that the
      body weight gain was significantly lower in sirolimus-treated rats. Sirolimus
      reduced portal pressure and plasma levels of alanine aminotransferase, aspartate
      aminotransferase and ammonia, and attenuated hepatic inflammation and fibrosis in
      cirrhotic rats. In addition, the hepatic phosphorylated mammalian target of
      rapamycin (mTOR) and P70S6K protein expressions were significantly downregulated
      and endothelial nitric oxide synthase (eNOS) expression upregulated by sirolimus.
      Sirolimus did not influence portal-systemic shunting and motor activities of
      cirrhotic rats. In conclusion, sirolimus significantly improved hepatic
      inflammation and fibrosis accompanied by portal pressure reduction in cirrhotic
      rats, in which down-regulated mTOR/P70S6K and up-regulated eNOS expressions might
      play a role. However, sirolimus did not significantly change the severity of
      portal-systemic collaterals and motor activities, suggesting that the
      multifactorial pathogenesis of hepatic encephalopathy could not be fully overcome
      by sirolimus.

PMID- 29444471
TI  - Optimization of the polysaccharide hydrolysate from Auricularia auricula with
      antioxidant activity by response surface methodology.
AB  - An efficient acid-hydrolysis method was developed and optimized for the
      hydrolyses of polysaccharide from Auricularia auricula with the ABTS. scavenging
      ability as the detective marker. Based on the single factor experimental results,
      Box-Behnken design (BBD) were applied for the optimization of acid-hydrolysis
      conditions. The possible antioxidant mechanism of the hydrolyses (AAPs-F) in vivo
      was performed using the C. elegans model. The acid-hydrolysis conditions were
      found to be the optimal hydrolyzing time 2.78h (166.8min), hydrolyzing
      temperature 95.04 degrees C and the acid concentration 14.03mol/L, respectively.
      Under the optimal acid-hydrolysis conditions, the ABTS. scavenging ability of
      AAPs-H was 97.94+/-0.87%, which was well matched with the predicted value
      (99.77%) of the BBD model. AAPs-F was the main fraction of AAPs-H separated
      through Sephadex G-10 as the stationary phase. AAPs-F was a kind of
      heteropolysaccharide and comprised of glucose, galactose and fucose with the
      molar ratio of 50:1:2. The molecular weight of AAPs-F was 143.15kDa. AAPs-F
      showed a remarkable protective effect to the injury induced by hydrogen peroxide
      or paraquat (p<0.01), and it could up-regulate stress-resistance related enzymes
      including superoxide dismutase (SOD) by 109.74% and CAT by 106.84% at
      concentration of 0.2mg/mL in C. elegans.

PMID- 29444472
TI  - Low-resolution SAXS and comparative modeling based structure analysis of endo
      beta-1,4-xylanase a family 10 glycoside hydrolase from Pseudopedobacter saltans
      comb. nov.
AB  - The structure and biophysical properties of endo beta-1,4-xylanase (PsGH10A) of
      family 10 glycoside hydrolase were characterized. The modeled PsGH10A structure
      showed classical (beta/alpha)8-barrel fold. Ramachandran plot displayed 99.1%
      residues in favored and 0.3% in the generously allowed region and only 0.6%
      residues in disallowed region. The secondary structure analysis of PsGH10A by CD
      revealed 31.75% alpha-helices 20.0% beta-strands and 48.25% random coils. Protein
      melting study of PsGH10A showed complete unfolding at 60 degrees C and did not
      require any metal ion for its stability. Structural superposition and docking
      analysis confirmed the involvement of Glu156 and Glu263 residues in catalysis.
      SAXS analysis displayed that PsGH10A is monomeric in nature showing fully folded
      state in solution form. Guinier analysis gave the radius of gyration (Rg) 2.23
      2.29nm. Kratky plot indicated that the protein is fully folded globular shaped
      and flexible in solution form. The ab initio derived dummy model of PsGH10A
      displayed chicken thigh like shape. The ab initio derived dummy model superposed
      well with its comparative modeled structure except the N-terminal His-tag region.

PMID- 29444473
TI  - Adhesive properties of calcium pectinate gels prepared from callus cultures
      pectins.
AB  - The aim of this research is to investigate the influence of the surface
      morphology of the calcium pectinate gel (CaPG) beads as well as the
      physicochemical characteristics of pectins and the CaPG beads on the adhesive
      properties of gels against the Gram-negative bacteria Escherichia coli and the
      Gram-positive bacteria Bacillus subtilis. The adhesion of the bacteria depends on
      the type of pectin and the surface morphology of the beads. The faster adhesion
      on CaPG beads appeared to be related to a lower degree of methyl esterification
      (DE), a higher molecular weight (Mw) and specific viscosity of the pectin and a
      higher gel strength. Surface roughness measurements were performed using an
      atomic force microscope. The beads from pectins with a higher Mw, a higher
      specific viscosity and a lower DE had a higher surface roughness. The surface
      roughness was one of the factors promoting adhesion of the bacteria onto the
      calcium pectinate gels. The surface morphology was observed under a scanning
      electron microscope (SEM). SEM images illustrated that E. coli and B. subtilis
      adhered on the beads with a rough surface. CaPG beads obtained from callus
      culture pectins can be proposed for the preparation of gels with adhesive and
      antiadhesive properties.

PMID- 29444474
TI  - DNA-directed trypsin immobilization on a polyamidoamine dendrimer-modified
      capillary to form a renewable immobilized enzyme microreactor.
AB  - A novel type of trypsin capillary microreactor was developed based on a DNA
      directed immobilization (DDI) technique applied to a fused-silica capillary
      modified with polyamidoamine (PAMAM) dendrimers. Trypsin binding to the inner
      wall of the capillary was confirmed by confocal laser scanning microscopy. The
      properties of the trypsin-DNA conjugated, PAMAM-modified capillary microreactor
      were investigated by monitoring hydrolysis of Nalpha-benzoyl-L-arginine ethyl
      ester. Through the hybridization and dehybridization of the DNA, the inner wall
      of the capillary functionalized with trypsin can be regenerated, thus indicating
      the renewability of this enzyme microreactor. In addition, these results
      demonstrated that introduction of PAMAM enabled higher amounts of trypsin to be
      immobilized, markedly improving the enzymolysis efficiency, compared with
      traditional modified capillaries. The digestion performance of the trypsin
      capillary microreactor was further evaluated by digesting cytochrome C, and a
      peptide numbers of 8, and a sequence coverage of 59% were obtained. This
      renewable and efficient immobilized trypsin capillary microreactor combines
      advantages of both DDI technology and PAMAM, and is potentially adaptable to high
      throughput enzyme assays in biochemical and clinical research.

PMID- 29444475
TI  - Efficient Recombinase-Mediated Cassette Exchange in hPSCs to Study the Hepatocyte
      Lineage Reveals AAVS1 Locus-Mediated Transgene Inhibition.

PMID- 29444476
TI  - Retraction Notice to: In Vitro Modeling of Blood-Brain Barrier with Human iPSC
      Derived Endothelial Cells, Pericytes, Neurons, and Astrocytes via Notch
      Signaling.

PMID- 29444477
TI  - The microbiome in chronic kidney disease patients undergoing hemodialysis and
      peritoneal dialysis.
AB  - Chronic kidney disease (CKD) is associated with an imbalanced human microbiome
      due not only to CKD-associated factors such as uremia, increased inflammation and
      immunosuppression, but also to pharmacological therapies and dietary
      restrictions. End-stage renal disease patients require renal replacement
      therapies commonly in the form of hemodialysis (HD) or peritoneal dialysis (PD).
      HD implies the existence of a vascular access, such as an arteriovenous
      fistula/graft or a venous catheter, whereas PD implies a long-term peritoneal
      catheter and the constant inflow of peritoneal dialysate. Also, dietary
      adaptations are mandatory in both therapies. This revision explores the impact of
      HD or PD therapies on human microbiome. HD and PD appear to be associated with
      different changes in the gut microbiome, for example a decrease in Proteobacteria
      relative abundance in HD patients and increase in PD patients. Both therapies may
      also have an impact on the human microbiome beyond the gut, leading to increased
      relative abundance of specific bacteria in the blood microbiome of HD patients
      and increased relative abundance of other bacteria in the peritoneal microbiome
      of PD patients. HD and PD catheter biofilms may also play an important role in
      the changes observed in these microbiomes. A more interdisciplinary approach is
      needed to further clarify the role of microbial groups other than bacteria in all
      body habitats to allow the complete understanding of the impact of HD or PD on
      the microbiome of CKD patients. Moreover, strategies that promote a healthy
      balance of the human microbiome on these patients should be explored.

PMID- 29444478
TI  - Detection of drug safety signals from clinical trials data: Role of SUSARs.
AB  - One of the main goals of safety management in clinical trials is to detect
      suspected unexpected serious adverse reactions (SUSARs). The unexpectedness
      concerns the nature, frequency or severity of an adverse reaction. Drug safety
      signals could thus be retrieved, and a study was performed to investigate whether
      SUSARs allow signal detection in pharmacovigilance. Data from six academic safety
      units were collected from 2005 to 2016. Characteristics of SUSARs were analysed
      and signals were identified i) by evaluating the presence of other causes, ii) by
      assessing the summary of product characteristics (SPC), iii) by searching for
      specific safety information in Pubmed and health agencies, and iv) by
      investigating the narrative of each case. Pharmacological plausibility was
      evaluated by compatible mechanism of reaction and time-to-onset. During the study
      period, 211 SUSARs were collected. They mostly concerned general disorders
      (26.1%) and protein kinase inhibitors (24.6%). After eliminating SUSARs with
      other causes or those considered as expected, 50 SUSARs (23.7%), involving a
      total of 115 drug-reaction pairs, concerned potential safety signals. Among these
      pairs, 12 (10.4%) were considered as pharmacologically plausible. This study
      indicates that one quarter of SUSARs collected in academic clinical trials refers
      to potential safety signals, especially for oncologic drugs. One tenth of drug
      reaction pairs was considered to have a pharmacological plausibility and could
      merit further evaluation. This is the first study suggesting that SUSARs could be
      a source of safety signals and that their routine analysis should be
      complementary to spontaneous reporting.

PMID- 29444479
TI  - Prevalence and correlates of burnout in health professionals in Ecuador.
AB  - BACKGROUND: Although burnout is a widespread phenomenon among healthcare
      professionals, there are no studies about its prevalence in Ecuador. This study
      assesses the prevalence of burnout syndrome among Ecuadorian healthcare
      professionals and examine the relationship with their personal and organizational
      characteristics. METHODS: A total of 2404 healthcare professionals (average age
      40.0years; 68.4% women) from the capitals of all 24 provinces in Ecuador
      participated in this study. Trained psychologists assessed the presence of
      burnout by applying the Maslach Burnout Inventory. Sociodemographic variables,
      emotional distress, social support and coping styles as well as organizational
      variables were also collected. RESULTS: Of all healthcare professionals surveyed,
      2.6% presented burnout syndrome. By dimensions, 17.2% of the participants
      presented a high level of emotional exhaustion, 13.5% of depersonalization, and
      18.2% had reduced personal accomplishment. Being non-mestizo, being classified as
      a probable case of mental disorder and using more passive coping were associated
      with a greater probability of presenting burnout; having >10years of experience
      was associated with a lower probability of burnout. CONCLUSIONS: A significant
      number of active health professionals suffer from burnout. It is necessary to
      develop effective psychotherapeutic interventions for those who have the syndrome
      and to evaluate potential prevention strategies in those who have not yet
      developed it.

PMID- 29444481
TI  - Extreme weather impacts on tropical mangrove forests in the Eastern Brazil Marine
      Ecoregion.
AB  - Extreme weather events are likely to become more frequent in the 21st century
      bringing significant impacts to coastal ecosystems. However, the capacity to
      detect and measure those impacts are still limited, with effects largely
      unstudied. In June 2016, a hailstorm with wind gusts of over 100 km.h-1 caused an
      unprecedented mangrove dieback on Eastern Brazil. To quantify the scale of impact
      and short-term recovery of mangroves (15-mo), we used satellite imagery and field
      sampling to evaluate changes in forest structure in control and impacted areas
      after the hailstorm. Satellite imagery revealed mangrove dieback in over 500 ha,
      corresponding to 29.3% of the total forest area suddenly impacted after the
      hailstorm. Fifteen months after the hailstorm, some impacted areas show an
      initial recovery, while others continued to degrade. The El Nino years of 2014
      2016 created mild drought conditions in Eastern Brazil. As observed in wetlands
      of semi-arid regions during the same period, mangrove recovery may have been
      impaired by continued physiological stress and climate change effects. Economic
      losses in the study site from typical mangrove ecosystem services including food
      provision, climate regulation, raw materials and nurseries are estimated to at
      least US$ 792,624 yr-1. This is the first evidence of an extreme weather impact
      on mangroves in Brazil that typically provide unique ecological and economic
      subsistence to coastal populations. Our results reveal that there is a pressing
      need for long-term monitoring and climate change adaptation actions for coastal
      wetlands in Brazil, and to provide broad estimates of ecosystem values associated
      with these ecosystems given many areas are already experiencing chronic stress
      from local impacts, drought and high temperatures.

PMID- 29444480
TI  - Does crash risk increase when emergency vehicles are driving with lights and
      sirens?
AB  - INTRODUCTION: Emergency vehicles, such as police, ambulances, and fire vehicles,
      need to arrive at the scene of emergencies as quickly as possible, and thus they
      often travel in emergency mode - using their lights and sirens and often
      bypassing traffic signals. We examined whether travelling in emergency mode
      increased crash risk among police, ambulance and fire vehicles. METHODS: We
      conducted a quasi-induced exposure analysis using data from the Iowa Crash
      Database for the period of 2005 through 2013. The data are maintained by the Iowa
      Department of Transportation (IADOT), Office of Driver Services (ODS) and
      includes all investigating police officer's reports of motor vehicle crashes. The
      quasi-induced exposure method is an approach to calculate crash risk in the
      absence of exposure data using vehicles without a contributing cause (did not
      contribute to the crash) as a proxy for the baseline driving population. RESULTS:
      From 2005 - 2013, police vehicles were involved in 2406 crashes and ambulances
      and fire vehicles were involved in 528 crashes. Police vehicles were 1.8 times
      more likely to crash while driving in emergency mode than usual mode; this was a
      statistically significant increase. Ambulance and fire vehicles were not more
      likely to crash in emergency mode compared with usual mode. For police, other
      factors that contributed to crash risk included gender, age, icy/snowy roads,
      unpaved roads, and intersections. For ambulances and fire vehicles, other factors
      that contributed to crash risk included gender, age, weekends, icy/snowy roads
      and urban locations. CONCLUSION: Crash risk increased when police vehicles drove
      with lights and sirens but did not increase for ambulance and fire vehicles.
      Further research is necessary to develop and evaluate strategies to mitigate
      crash risk among police vehicles. Cultural approaches which prioritize
      transportation safety in conjunction with reaching the scene as quickly as
      possible may be warranted.

PMID- 29444482
TI  - Exposure and risk assessment to arsenic species in Spanish children using
      biomonitoring.
AB  - We present a new approach to arsenic (As) risk assessment using biomonitoring. In
      this pilot study we determined the levels of total and speciated urinary
      arsenicin 109 Spanish school children aged between 6 and 11 years, and
      interpreted these concentrations in a risk assessment context. The geometric mean
      (GM) for total As (TAs) was 33.82 MU/L. The order of occurrence and average
      concentrations of the different species was arsenobetaine (AsB) (100%, 15 MUg/L),
      dimethylarsinic (DMA) (97%, 8.32 MUg/L), monomethylarsonic (MMA) (26%, 0.27
      MUg/L) and inorganic As (iAs) (4%, 0.14 MUg/L). 18% of children presented
      exposures to inorganic arsenic (7.52 MUg/g creatinine) higher than guidance value
      for non-cancer risk (8.3 MUg/g creatinine). For cancer risk the exposure to
      inorganic arsenic was much higher than the guidance value. Urinary DMA was
      positively associated with urinary AsB, suggesting exposure directly to this
      specie or metabolism of organic arsenicals to this specie, mainly through seafood
      consumption. Consequently, the exposure to inorganic As needs to be carefully
      interpreted because it may be overestimated. Our study supports the hypothesis
      that urinary iAs + MMA is the most reliable biomarker of exposure to inorganic
      As.

PMID- 29444483
TI  - Nitrifying activity and ammonia-oxidizing microorganisms in a constructed wetland
      treating polluted surface water.
AB  - Ammonia oxidation, performed by both ammonia oxidizing bacteria (AOB) and archaea
      (AOA), is an important step for nitrogen removal in constructed wetlands (CWs).
      However, little is known about the distribution of these ammonia oxidizing
      organisms in CWs and the associated wetland environmental variables. Their
      relative importance to nitrification in CWs remains still controversial. The
      present study investigated the seasonal dynamics of AOA and AOB communities in a
      free water surface flow CW (FWSF-CW) used to ameliorate the quality of polluted
      river water. Strong seasonality effects on potential nitrification rate (PNR) and
      the abundance, richness, diversity and structure of AOA and AOB communities were
      observed in the river water treatment FWSF-CW. PNR was positively correlated to
      AOB abundance. AOB (6.76*105-6.01*107 bacterial amoA gene copies per gram dry
      sediment/soil) tended to be much more abundant than AOA (from below quantitative
      PCR detection limit to 9.62*106 archaeal amoA gene copies per gram dry
      sediment/soil). Both AOA and AOB abundance were regulated by the levels of
      nitrogen, phosphorus and organic carbon. Different wetland environmental
      variables determined the diversity and structure of AOA and AOB communities.
      Wetland AOA communities were mainly composed of unknown species and
      Nitrosopumilus-like organisms, while AOB communities were mainly represented by
      both Nitrosospira and Nitrosomonas.

PMID- 29444484
TI  - Application of a new targeted low density microarray and conventional biomarkers
      to evaluate the health status of marine mussels: A field study in Sardinian
      coast, Italy.
AB  - In the present study, we investigated the health status of marine mussels
      (Mytilus galloprovincialis) caged and deployed at three different sites on the
      Sardinian coastline characterized by different levels of contamination: Fornelli
      (F, the reference site), Cala Real (CR), and Porto Torres (PT). A new low density
      oligonucleotide microarray was used to investigate global gene expression in the
      digestive gland of mussels. Target genes were selected to cover most of the
      biological processes involved in the stress response in bivalve mollusks (e.g.
      DNA metabolism, translation, immune response, cytoskeleton organization). A
      battery of classical biomarkers was also employed to complement the gene
      expression analyses. Chemical analysis revealed higher loads of heavy metals (Pb
      and Cu) and total polycyclic aromatic hydrocarbons (PAHs) at PT compared to the
      other sites. In mussels deployed at CR, functional genomics analysis of the
      microarray data rendered 78 differentially expressed genes (DEGs) involved in 11
      biological processes. Animals exposed at PT had 105 DEGs that were characterized
      by the regulation of 14 biological processes, including mitochondrial activity,
      adhesion to substrate, DNA metabolism, translation, metal resistance, and
      cytoskeleton organization. Biomarker data (lysosomal membrane stability,
      lysosomal/cytoplasm volume ratio, lipofuscin accumulation, metallothionein
      content, micronucleus frequency, and cytoskeleton alteration) were in trend with
      transcriptomic output. Biomarker data were integrated using the Mussel Expert
      System (MES), allowing defining the area in which the presence of chemicals is
      toxic for mussels. Our study provides the opportunity to adopt a new approach of
      integrating transcriptomic (microarray) results with classical biomarkers to
      assess the impact of pollutants on marine mussels in biomonitoring programs.

PMID- 29444485
TI  - Estimating subcooled liquid vapor pressures and octanol-air partition
      coefficients of polybrominated diphenyl ethers and their temperature dependence.
AB  - Both subcooled liquid vapor pressure (PL) and octanol-air partition coefficient
      (KOA) are widely used as descriptors to predict gas-particle partitioning
      behavior of semi-volatile organic compounds (SVOCs), such as polybrominated
      diphenyl ethers (PBDEs). These two descriptors are functions of temperature,
      which are expressed as the Clausius-Clapeyron equations with the coefficients AL
      and BL for PL (log PL=AL+BL/T) and AO and BO for KOA (log KOA=AO+BO/T), where T
      is temperature in K. In this study, a simple equation to relate log KOA and log
      PL (log KOA=-log PL+6.46) was derived, which also links the coefficients of AL
      &BL and AO &BO. Regression analysis of published data of internal energy DeltaUOA
      for 22 PBDE congeners with their mole mass was made, leading a regression
      equation to calculate the internal energy for all 209 PBDE congeners. Three
      datasets of log KOA at 25 degrees C for all 209 PBDE congeners were evaluated;
      the one with the best match with experimentally measurements was selected. Using
      the datasets and equations described above, we calculated the values of Clausius
      Clapeyron coefficients AO &BO and AL &BL for all 209 PBDE congeners at the
      following steps. First, BO was computed using the values of DeltaUOA. Next, we
      calculated the values of AO using the values of BO and the values of log KOA at
      25 degrees C. Finally, the values of the parameter AL and BL were determined for
      all 209 PBDE congeners. Results are in consistent with data available in the
      literature and the accuracy of the data were also evaluated. With these Clausius
      Clapeyron coefficients, the values of PL and KOA at any environmentally relevant
      temperature can be calculated for all 209 PBDE congeners, and thus provides a
      quick reference for environmental monitoring and modeling of PBDEs.

PMID- 29444486
TI  - Brook trout distributional response to unconventional oil and gas development:
      Landscape context matters.
AB  - We conducted a large-scale assessment of unconventional oil and gas (UOG)
      development effects on brook trout (Salvelinus fontinalis) distribution. We
      compiled 2231 brook trout collection records from the Upper Susquehanna River
      Watershed, USA. We used boosted regression tree (BRT) analysis to predict
      occurrence probability at the 1:24,000 stream-segment scale as a function of
      natural and anthropogenic landscape and climatic attributes. We then evaluated
      the importance of landscape context (i.e., pre-existing natural habitat quality
      and anthropogenic degradation) in modulating the effects of UOG on brook trout
      distribution under UOG development scenarios. BRT made use of 5 anthropogenic
      (28% relative influence) and 7 natural (72% relative influence) variables to
      model occurrence with a high degree of accuracy [Area Under the Receiver
      Operating Curve (AUC)=0.85 and cross-validated AUC=0.81]. UOG development
      impacted 11% (n=2784) of streams and resulted in a loss of predicted occurrence
      in 126 (4%). Most streams impacted by UOG had unsuitable underlying natural
      habitat quality (n=1220; 44%). Brook trout were predicted to be absent from an
      additional 26% (n=733) of streams due to pre-existing non-UOG land uses (i.e.,
      agriculture, residential and commercial development, or historic mining). Streams
      with a predicted and observed (via existing pre- and post-disturbance fish
      sampling records) loss of occurrence due to UOG tended to have intermediate
      natural habitat quality and/or intermediate levels of non-UOG stress. Simulated
      development of permitted but undeveloped UOG wells (n=943) resulted in a loss of
      predicted occurrence in 27 additional streams. Loss of occurrence was strongly
      dependent upon landscape context, suggesting effects of current and future UOG
      development are likely most relevant in streams near the probability threshold
      due to pre-existing habitat degradation.

PMID- 29444489
TI  - Continuous directed evolution for strain and protein engineering.
AB  - Continuous directed evolution is the 'while loop' of synthetic biology,
      autonomous cycles of mutation, selection, and self-replication that can lead to
      the rapid development of industrially relevant organisms, pathways, or molecules.
      Although this engineering strategy requires particular mutagenesis methods and
      well-defined selections, recent advances have facilitated its implementation.
      Control over selection pressure has been augmented by novel cost-effective
      continuous culturing devices with open source designs. New in vivo targeted
      mutagenesis methods have enabled continuous directed protein evolution in various
      organisms. Furthermore, advances in automation have enabled rational, semi
      continuous directed evolution strategies that may yield fewer artefacts or
      parasites. Overall, continuous directed evolution is persistently demonstrating
      its capacity to rapidly generate biotechnologically valuable strains and
      proteins.

PMID- 29444487
TI  - Paracrine Fibroblast Growth Factor Initiates Oncogenic Synergy with Epithelial
      FGFR/Src Transformation in Prostate Tumor Progression.
AB  - Cross talk of stromal-epithelial cells plays an essential role in both normal
      development and tumor initiation and progression. Fibroblast growth factor (FGF)
      FGF receptor (FGFR)-Src kinase axis is one of the major signal transduction
      pathways to mediate this cross talk. Numerous genomic studies have demonstrated
      that expression levels of FGFR/Src are deregulated in a variety of cancers
      including prostate cancer; however, the role that paracrine FGF (from stromal
      cells) plays in dysregulated expression of epithelial FGFRs/Src and tumor
      progression in vivo is not well evaluated. In this study, we demonstrate that
      ectopic expression of wild-type FGFR1/2 or Src kinase in epithelial cells was not
      sufficient to initiate prostate tumorigenesis under a normal stromal
      microenvironment in vivo. However, paracrine FGF10 synergized with ectopic
      expression of epithelial FGFR1 or FGFR2 to induce epithelial-mesenchymal
      transition. Additionally, paracrine FGF10 sensitized FGFR2-transformed epithelial
      cells to initiate prostate tumorigenesis. Next, paracrine FGF10 also synergized
      with overexpression of epithelial Src kinase to high-grade tumors. But loss of
      the myristoylation site in Src kinase inhibited paracrine FGF10-induced prostate
      tumorigenesis. Loss of myristoylation alters Src levels in the cell membrane and
      inhibited FGF-mediated signaling including inhibition of the phosphotyrosine
      pattern and FAK phosphorylation. Our study demonstrates the potential tumor
      progression by simultaneous deregulation of proteins in the FGF/FGFRs/Src signal
      axis and provides a therapeutic strategy of targeting myristoylation of Src
      kinase to interfere with the tumorigenic process.

PMID- 29444488
TI  - Challenges and opportunities for large-scale electrophysiology with Neuropixels
      probes.
AB  - Electrophysiological methods are the gold standard in neuroscience because they
      reveal the activity of individual neurons at high temporal resolution and in
      arbitrary brain locations. Microelectrode arrays based on complementary metal
      oxide semiconductor (CMOS) technology, such as Neuropixels probes, look set to
      transform these methods. Neuropixels probes provide ~1000 recording sites on an
      extremely narrow shank, with on-board amplification, digitization, and
      multiplexing. They deliver low-noise recordings from hundreds of neurons,
      providing a step change in the type of data available to neuroscientists. Here we
      discuss the opportunities afforded by these probes for large-scale
      electrophysiology, the challenges associated with data processing and anatomical
      localization, and avenues for further improvements of the technology.

PMID- 29444490
TI  - Systematic evaluation of matrix effects in supercritical fluid chromatography
      versus liquid chromatography coupled to mass spectrometry for biological samples.
AB  - Matrix effects (ME) is acknowledged as being one of the major drawbacks of
      quantitative bioanalytical methods, involving the use of liquid chromatography
      coupled to mass spectrometry (LC-MS). In the present study, the incidence of ME
      in SFC-MS/MS and LC-MS/MS in the positive mode electrospray ionization (ESI+) was
      systematically compared for the analysis of urine and plasma samples using two
      representative sets of 40 doping agents and 38 pharmaceutical compounds,
      respectively. Three different SFC stationary phase chemistries were employed, to
      highlight the importance of the column in terms of selectivity. Biological
      samples were prepared using two different sample treatments, including a non
      selective sample clean-up procedure (dilute and shoot (DS) and protein
      precipitation (PP) for urine and plasma samples, respectively) and a selective
      sample preparation, namely solid phase extraction (SPE) for both matrices. The
      lower susceptibility to ME in SFC vs. reversed phase LC (RPLC) was verified in
      all the experiments performed on urine, and especially when a simple DS procedure
      was applied. Also, with the latter, the performance strongly varied according to
      the selected SFC stationary phase, whereas the results were quite similar with
      the three SFC columns, in the case of SPE clean-up. The same trend was observed
      with plasma samples. Indeed, with the PP procedure, the occurrence of ME was
      different on the three SFC columns, and only the 2-picolylamine stationary phase
      chemistry displayed lower incidence of ME compared to LC-MS/MS. On the contrary,
      when a SPE clean-up was carried out, the results were similar to the urine
      samples, with higher performance of SFC vs. LC and limited discrepancies between
      the three SFC columns. The type of ME observed in LC-MS/MS was generally a signal
      enhancement and an ion suppression for urine and plasma samples, respectively. In
      the case of SFC-MS/MS, the type of ME randomly varied according to the analyzed
      matrix, selected column and sample treatment.

PMID- 29444491
TI  - Piecing together nonribosomal peptide synthesis.
AB  - Nonribosomal peptide synthetases (NRPSs) produce peptide products with wide
      ranging biological activities. NRPSs are macromolecular machines with modular
      assembly-line logic, a complex catalytic cycle, moving parts and multiple active
      sites. They are organized into repeating sets of domains, called modules. Each
      module contains all functionality to introduce a building block into the growing
      peptide, many also perform cosynthetic tailoring. Structures of individual
      domains have provided insights into their catalytic mechanisms, but with one
      exception, larger NRPS proteins were refractory to structure determination.
      Recently, structure determination succeeded for four multi-domain NRPS proteins:
      an alternative formylating initiation and two termination modules as well as a
      large cross-module construct. This review highlights how these data, together
      with novel didomain structures, contribute to a holistic view of the
      architecture, domain-domain interactions and conformational changes in NRPS
      megaenzymes.

PMID- 29444492
TI  - Editorial overview: Bacterial cell regulation: from genes to complex
      environments.

PMID- 29444494
TI  - Terahertz time-domain attenuated total reflection spectroscopy applied to the
      rapid discrimination of the botanical origin of honeys.
AB  - A new technique to identify the floral resources of honeys is demanded. Terahertz
      time-domain attenuated total reflection spectroscopy combined with chemometrics
      methods was applied to discriminate different categorizes (Medlar honey, Vitex
      honey, and Acacia honey). Principal component analysis (PCA), cluster analysis
      (CA) and partial least squares-discriminant analysis (PLS-DA) have been used to
      find information of the botanical origins of honeys. Spectral range also was
      discussed to increase the precision of PLS-DA model. The accuracy of 88.46% for
      validation set was obtained, using PLS-DA model in 0.5-1.5THz. This work
      indicated terahertz time-domain attenuated total reflection spectroscopy was an
      available approach to evaluate the quality of honey rapidly.

PMID- 29444495
TI  - Using an optimal CC-PLSR-RBFNN model and NIR spectroscopy for the starch content
      determination in corn.
AB  - Corn starch is an important material which has been traditionally used in the
      fields of food and chemical industry. In order to enhance the rapidness and
      reliability of the determination for starch content in corn, a methodology is
      proposed in this work, using an optimal CC-PLSR-RBFNN calibration model and near
      infrared (NIR) spectroscopy. The proposed model was developed based on the
      optimal selection of crucial parameters and the combination of correlation
      coefficient method (CC), partial least squares regression (PLSR) and radial basis
      function neural network (RBFNN). To test the performance of the model, a standard
      NIR spectroscopy data set was introduced, containing spectral information and
      chemical reference measurements of 80 corn samples. For comparison, several other
      models based on the identical data set were also briefly discussed. In this
      process, the root mean square error of prediction (RMSEP) and coefficient of
      determination (Rp2) in the prediction set were used to make evaluations. As a
      result, the proposed model presented the best predictive performance with the
      smallest RMSEP (0.0497%) and the highest Rp2 (0.9968). Therefore, the proposed
      method combining NIR spectroscopy with the optimal CC-PLSR-RBFNN model can be
      helpful to determine starch content in corn.

PMID- 29444496
TI  - A colorimetric platform for sensitively differentiating telomere DNA with
      different lengths, monitoring G-quadruplex and dsDNA based on silver nanoclusters
      and unmodified gold nanoparticles.
AB  - Human telomere DNA plays a vital role in genome integrity control and
      carcinogenesis as an indication for extensive cell proliferation. Herein, silver
      nanoclusters (Ag NCs) templated by polymer and unmodified gold nanoparticles (Au
      NPs) are designed as a new colorimetric platform for sensitively differentiating
      telomere DNA with different lengths, monitoring G-quadruplex and dsDNA. Ag NCs
      can produce the aggregation of Au NPs, so the color of Au NPs changes to blue and
      the absorption peak moves to 700nm. While the telomere DNA can protect Au NPs
      from aggregation, the color turns to red again and the absorption band blue
      shift. Benefiting from the obvious color change, we can differentiate the length
      of telomere DNA by naked eyes. As the length of telomere DNA is longer, the
      variation of color becomes more noticeable. The detection limits of telomere DNA
      containing 10, 22, 40, 64 bases are estimated to be 1.41, 1.21, 0.23 and 0.22nM,
      respectively. On the other hand, when telomere DNA forms G-quadruplex in the
      presence of K+, or dsDNA with complementary sequence, both G-quadruplex and dsDNA
      can protect Au NPs better than the unfolded telomere DNA. Hence, a new
      colorimetric platform for monitoring structure conversion of DNA is established
      by Ag NCs-Au NPs system, and to prove this type of application, a selective K+
      sensor is developed.

PMID- 29444493
TI  - Modulators of innate immunity as novel therapeutics for treatment of chronic
      hepatitis B.
AB  - The first line defense mechanisms against viral infection are mediated by the
      innate immune system. Viral components are detected by infected cells and/or
      innate immune cells that express different sensory receptors. They in turn
      mediate induction of direct antiviral mechanisms and further modulation of innate
      and adaptive immune responses. For evading the innate system, most viruses have
      evolved efficient mechanisms to block sensing and/or antiviral functions of the
      innate response. Interestingly, hepatitis B virus (HBV) seems to act like a
      stealth virus that escapes cell intrinsic antiviral mechanisms through avoiding
      recognition by the innate system rather than blocking its effector functions. In
      line with this concept, agonistic activation of innate immunity has emerged as a
      promising novel anti-HBV therapy approach with several compounds having advanced
      to the clinical stage.

PMID- 29444497
TI  - Influence of the type of aqueous sodium silicate on the stabilization and
      rheology of kaolin clay suspensions.
AB  - To avoid agglomeration and sedimentation of grains, ceramic slurries should be
      modified by stabilizers in order to increase the electrostatic interactions
      between the dispersed particles. In this study we present the spectral analysis
      of aqueous sodium silicates obtained by different synthesis methods and their
      influence on the rheological properties of kaolin based slurries. Infrared and
      Raman spectra can be used to describe the structure of silicate structural units
      present in aqueous sodium silicates. It was confirmed that the best stabilization
      results possess aqueous sodium silicates of the silicate moduli of about 2 and
      the optimal concentration of the used fluidizer is 0.3wt% to the kaolin clay dry
      mass. One of the most important conclusions is that the synthesis method of the
      fluidizer has no significant effect on its stabilization properties but used
      medium does create adequate stabilization mechanism depending on the silicate
      structures present in the sodium silicate solution.

PMID- 29444498
TI  - A novel dicyanoisophorone based red-emitting fluorescent probe with a large
      Stokes shift for detection of hydrazine in solution and living cells.
AB  - A novel dicyanoisophorone based fluorescent probe HP was developed to detect
      hydrazine. Upon the addition of hydrazine, probe HP displayed turn-on
      fluorescence in the red region with a large Stokes shift (180nm). This probe
      exhibited high selectivity and high sensitivity to hydrazine in solution. The
      detection limit of HP was found to be 3.26ppb, which was lower than the threshold
      limit value set by USEPA (10ppb). Moreover, the probe was successfully applied to
      detect hydrazine in different water samples and living cells.

PMID- 29444499
TI  - Fine tuning the emission wavelengths of the 7-hydroxy-1-indanone based nano
      structure dyes: Near-infrared (NIR) dual emission generation with large stokes
      shifts.
AB  - Near-infrared (NIR) fluorescent dyes have recently gained special attention due
      to their applications to use as molecular probes for imaging of biological
      targets and sensitive determination. In this study, photophysical properties of
      the 7-hydroxy-1-indanone based fluorophors A1, A2, A3, B1, B2 and 3R-B2 (R=CF3,
      NH2, NO2 and OMe) in the gas and three solution phases were probed using TD-DFT
      method at PBE0/6-311++G(d,p) and M06-2X/6-311++G(d,p) levels of theory. In
      addition to structural and photophysical properties as well as ESIPT mechanism of
      all mentioned molecules, the FC and relaxed potential energy surfaces of B2 and
      3R-B2 (R=CF3 and NH2) molecules were explored in gas phase and acetonitrile,
      cyclohexane and water solvents. It is predicted that the A1, A3 and 3R-B2
      chromophores afford normal (615-670nm) and NIR fluorescence emissions (770-940nm;
      biological window) with the large Stokes shifts of >160 and >300nm, respectively.
      A good aggrement was found between theoretical and experimental results. In sum,
      these new types of dyes may render the new approaches for the development of the
      most efficient NIR fluorescent probes for enhanced image contrast and optimal
      apparent brightness in biological applications.

PMID- 29444500
TI  - Generation of induced pluripotent stem cell line (ZZUi004-A) from urine sample of
      a patient with spinocerebellar ataxia type 3.
AB  - Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative
      disease caused by a CAG repeat expansion in the region of the ATXN3 gene. The
      main feature of SCA3 is progressive ataxia, which affects balance, gait, and
      speech. Urine cells (UCs) of a SCA3 patient were successfully translated to
      induced pluripotent stem cells (iPSCs) by using the Sendai virus delivery system.
      ZZUi004-A cell line may provide a robust platform for further study of SCA3
      pathogenesis as well as drug testing and gene therapy research.

PMID- 29444501
TI  - Quercetin Therapy for Selected Patients with PIM1 Kinase-Positive Chronic
      Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pilot Study.
AB  - We reported that PIM1 kinase is expressed in the lymphocytes of patients with
      chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Quercetin, a
      naturally occurring flavonoid, is a dietary supplement and inhibits many kinases,
      including PIM1, in vitro. Under an Institutional Review Board-approved protocol,
      we performed an open-label, single-arm pilot study to evaluate the antitumor
      activity of quercetin in patients with CLL/SLL. Q-ForceTM chews were administered
      orally, 500 mg twice daily, for 3 months. Eligible patients had failed prior
      therapies, had had no other standard treatment, or refused other therapies.
      Response was assessed based on objective change in disease parameters. Patients
      were included if their lymphocyte counts were rising and >=10,000/uL but not >
      100,000/uL. Three patients received quercetin treatment. There was no toxicity.
      Two responded with stabilization of rising lymphocyte counts (p < 0.001 for
      each), which remained stable during their follow-up (5 and 11 months after
      cessation of treatment, respectively). The CLL cells in the nonresponder harbored
      a TP53 mutation. Although our data from this pilot translational study are based
      on a small sample, further studies of quercetin as a potential therapeutic agent
      in selected patients with CLL/SLL appear warranted.

PMID- 29444502
TI  - Starch Combined with Sucrose Provokes Greater Root Dentine Demineralization than
      Sucrose Alone.
AB  - Since there is no consensus about whether starch increases the cariogenic
      potential of sucrose, we used a validated 3-species biofilm model to evaluate if
      starch combined with sucrose provokes higher root dentine demineralization than
      sucrose alone. Biofilms (n = 18) composed by Streptococcus mutans (the most
      cariogenic bacteria), Actinomces naeslundii (which has amylolytic activity), and
      Streptococcus gordonii (which binds salivary amylase) were formed on root dentine
      slabs under exposure 8 */day to one of the following treatments: 0.9% NaCl, 1%
      starch, 10% sucrose, or a combination of 1% starch and 10% sucrose. Before each
      treatment, biofilms were pretreated with human whole saliva for 1 min. The pH of
      the culture medium was measured daily as an indicator of biofilm acidogenicity.
      After 96 h of growth, the biofilms were collected, and the biomass, bacteria
      viability, and polysaccharides were analyzed. Dentine demineralization was
      assessed by surface hardness loss (% SHL). Biofilm bioarchitecture was analyzed
      using confocal laser scanning microscopy. Treatment with a starch and sucrose
      combination provoked higher (p = 0.01) dentine demineralization than sucrose
      alone (% SHL = 53.2 +/- 7.0 vs. 43.2 +/- 8.7). This was supported by lower pH
      values (p = 0.007) of the culture medium after daily exposure to the starch and
      sucrose combination compared with sucrose (4.89 +/- 0.29 vs. 5.19 +/- 0.32).
      Microbiological and biochemical findings did not differ between biofilms treated
      with the combination of starch and sucrose and sucrose alone (p > 0.05). Our
      findings give support to the hypothesis that a starch and sucrose combination is
      more cariogenic for root dentine than sucrose alone.

PMID- 29444503
TI  - Whither the Bone Marrow Transplantation in Multiple Myeloma?

PMID- 29444505
TI  - No Mutation Left Behind: The Impact of Reporting Recurrent Genetic Abnormalities
      on Outcomes of Patients with Acute Myeloid Leukemia.

PMID- 29444504
TI  - The SNP Rs915014 in MTHFR Regulated by MiRNA Associates with Atherosclerosis.
AB  - BACKGROUND/AIMS: The association between the genetic polymorphisms located in
      either the exon or untranslated region of MTHFR and the risk of human
      atherosclerosis has been well-documented. This study analyzed MTHFR polymorphisms
      at the 3'-untranslated region for association with risk and outcome of
      atherosclerosis in a Chinese Han population. METHODS: The hospital based case
      control study was conducted with 500 patients and 600 healthy volunteers as
      control enrolled. The genotyping was conducted by using Taqman probe. The
      potential interaction was predicted by multiple bioinformatics analysis. The
      relative expression of MTHFR was detected by qRT-PCR. Further confirmation was
      determined by dual-luciferase assay. The plasma homocysteine levels were assayed
      by ELISA. RESULTS: Cigarette smoking, alcohol consumption, diabetes, hypertension
      and low levels of serum high-density lipoprotein-C were associated with an
      increased risk of developing ischemic stroke. MTHFR rs915014 AG and GG genotypes
      were significantly associated with increased risk of rs915014 compared with the
      GG genotype. The qRT-PCR confirmed that MTHFR rs915014 AG or GG genotypes could
      facilitate miR-2861 binding leading to decreased MTHFR levels in cells. In
      addition, patients carrying the MTHFR rs915014 AG or GG genotypes were associated
      with accumulation of circulating tHcy volume and a poor atherosclerosis
      consequence. CONCLUSIONS: This study demonstrates that the MTHFR rs915014 is
      associated with increased risk of atherosclerosis and might be a shot term
      outcome biomarker for atherosclerosis patients.

PMID- 29444506
TI  - The Impact of Advanced Age on Driving Safety in Adults with Medical Conditions.
AB  - BACKGROUND: Adults aged 85 and older, often referred to as the oldest-old, are
      the fastest-growing segment of the population. The rapidly increasing number of
      older adults with chronic and multiple medical conditions poses challenges
      regarding their driving safety. OBJECTIVE: To investigate the effect of advanced
      age on driving safety in drivers with medical conditions. METHODS: We categorized
      3,425 drivers with preexisting medical conditions into four age groups: middle
      aged (55-64 years, n = 1,386), young-old (65-74 years, n = 1,013), old-old (75-84
      years, n = 803), or oldest-old (85 years and older, n = 223). All underwent a
      formal driving evaluation. The outcome measures included fitness to drive
      recommendation by the referring physician, comprehensive fitness to drive
      decision from an official driving evaluation center, history of motor vehicle
      crashes (MVCs), and history of traffic violations. RESULTS: The oldest-old
      reported more cardiopulmonary and visual conditions, but less neurological
      conditions than the old-old. Compared to the middle-aged, the oldest-old were
      more likely to be considered unfit to drive by the referring physicians (odds
      ratio [OR] = 4.47, 95% confidence interval [CI] 2.20-9.10) and by the official
      driving evaluation center (OR = 2.74, 95% CI 1.87-4.03). The oldest-old reported
      more MVCs (OR = 2.79, 95% CI 1.88-4.12) compared to the middle-aged. CONCLUSION:
      Advanced age adversely affected driving safety outcomes. The oldest-old are a
      unique age group with medical conditions known to interfere with safe driving.
      Driving safety strategies should particularly target the oldest-old since they
      are the fastest-growing group and their increased frailty is associated with
      severe or fatal injuries due to MVCs.

PMID- 29444507
TI  - High Uric Acid Inhibits Cardiomyocyte Viability Through the ERK/P38 Pathway via
      Oxidative Stress.
AB  - BACKGROUND/AIMS: Clinical studies have shown that hyperuricaemia is strongly
      associated with cardiovascular disease. However, the molecular mechanisms of high
      uric acid (HUA) associated with cardiovascular disease remain poorly understood.
      In this study, we investigated the effect of HUA on cardiomyocytes. METHODS: We
      exposed H9c2 cardiomyocytes to HUA, then cell viability was determined by MTT
      assay, and reactive oxygen species' (ROS) production was detected by a
      fluorescence assay. Western blot analysis was used to examine phosphorylation of
      extracellular signal-regulated kinase (ERK), p38, phosphatidylinositol 3-kinase
      (PI3K) and Akt. We monitored the impact of HUA on phospho-ERK and phospho-p38
      levels in myocardial tissue from an acute hyperuricaemia mouse model established
      by potassium oxonate treatment. RESULTS: HUA decreased cardiomyocyte viability
      and increased ROS production in cardiomyocytes; pre-treatment with N-acetyl-L
      cysteine, a ROS scavenger, and PD98059, an ERK inhibitor, reversed HUA-inhibited
      viability of cardiomyocytes. Further examination of signal transduction pathways
      revealed HUA-induced ROS involved in activating ERK/P38 and inhibiting PI3K/Akt
      in cardiomyocytes. Furthermore, the acute hyperuricaemic mouse model showed an
      increased phospho-ERK/p38 level in myocardial tissues. CONCLUSION: HUA induced
      oxidative damage and inhibited the viability of cardiomyocytes by activating
      ERK/p38 signalling, for a novel potential mechanism of hyperuricaemic-related
      cardiovascular disease.

PMID- 29444508
TI  - Negative Aging Stereotypes Disrupt both the Selection and Execution of Strategies
      in Older Adults.
AB  - BACKGROUND: Age-based cognitive deficits are exacerbated by stereotype threat
      effects (i.e., the threat of being judged as cognitively incapable due to aging).
      We tested whether age-based stereotype threat effects can occur via impair- ing
      older adults' ability to select the best strategy and/or to execute strategies
      efficiently. METHODS: Older adults (age range: 64.3-89.5 years) were randomly
      assigned to a stereotype threat or control condition before taking an episodic
      memory task. They encoded pairs of concrete words and of abstract words, with
      either a repetition or an imagery strategy, and then took a cued-recall task.
      Whereas participants in experiment 1 could choose between these two strategies,
      those of experiment 2 were forced to use either the repetition or the imagery
      strategy. RESULTS: Our findings showed that age-based stereotype threat disrupts
      both the selection and execution of the most efficient, but also most resource
      demanding, imagery strategy, and that these stereotype threat effects were
      stronger on concrete words. CONCLUSION: Our findings have important implications
      to further understand age-based (and other) stereotype threat effects, and how
      noncognitive factors modulate age-related changes in human cognition.

PMID- 29444509
TI  - Associations Between Intravenous Iron, Inflammation and FGF23 in Non-Dialysis
      Patients with Chronic Kidney Disease Stages 3-5.
AB  - BACKGROUND/AIMS: Both iron deficiency and chronic inflammation are highly
      prevalent in patients with chronic kidney disease (CKD). The effect of
      intravenous iron infusion on mineral metabolism in CKD may be modified by
      inflammation. Intravenous iron theraphy may reduce peripheral degradation,
      secretion, clearence of iFGF23 and lead to hypophosphatemia. The aim of the study
      was to evaluate the effect of intravenous iron on mineral metabolism in CKD
      patients. METHODS: 35 non-dialysis patients with CKD stages 3-5. received 100
      mg/24h of ferric oxide saccharated solution for 5 days. Serum calcium (Ca),
      phosphorus (P), parathormone (PTH), intact-FGF23 (iFGF23), C-terminal-FGF23
      (cFGF23), bone alkaline phosphatase (BAP) and high-sensitive CRP were assessed on
      day 1 and 3 at baseline and 2 hours after each dose administration and once on
      day 6. Plasma iFGF23 and cFGF23, as well as serum BAP were measured with ELISA
      and other parameters with standard automated laboratory methods. RESULTS: Serum
      iFGF23 increased after iv iron on day 1 and 6 (from 268.9+/-446.5 to 326.3+/
      529.9 on day 1; p=0.05 and to 451.4+/-601 pg/mL on day 6; p=0.03). cFGF23 was
      reduced only on day 1 (from 654.3+/-441.3 to 473.6+/-414 RU/mL; p=0.016). P
      concentration decreased significantly two hours after the first iron infusion
      (from 1.69+/-0.5 to 1.54+/-0.35 mmol/l; p=0.003). In following days the changes
      of cFGF23, P and of other calcium-phosphate metabolism were not significant.
      Serum CRP correlated neither with iFGF-23 nor cFGF-23. CONCLUSION: Intravenous
      iron supplementation may only transiently affect the production and degradation
      of FGF23 resulting in hypophosphatemia at the commencement of iron therapy.
      Chronic low-grade inflammation does not seem to play a role in that mechanism.

PMID- 29444510
TI  - Evaluating Serious Adverse Drug Reactions.

PMID- 29444511
TI  - Analysis of 10 Adrenocortical Carcinoma Patients in the Cohort of the Precision
      Medicine Platform MONDTI.
AB  - OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare disease with a dismal
      prognosis. We aimed to evaluate if a personalized medicine approach may be useful
      for matching patients with ACC to targeted therapies. METHODS: This is an
      analysis of 10 molecularly profiled ACCs that were progressing under standard of
      care treatment. The profile consisted of a 50-gene next-generation sequencing
      panel, immunohistochemistry (IHC), and fluorescence in situ hybridization for
      several proteins or chromosomal aberrations. RESULTS: In 6 (60%) tumor samples,
      no somatic mutation was detected, while in 3 (30%) tumors 1 mutation was detected
      and in 1 (10%) tumor 2 mutations were detected. These mutations were CTNNB1 (2
      samples), TP53 (1 sample), RB1 (1 sample) and APC (1 sample). Expression of
      phospho-mTOR and of EGFR was commonly detected by IHC (87.5 and 62.5%). In 4
      (50%) samples, IHC revealed a weak expression of progesterone receptor. Less
      frequent alterations were expression of PDGFR-alpha, c-KIT, and estrogen
      receptor, each in 1 case. CONCLUSIONS: Based on the molecular profile, no
      recommendation for targeted therapy was made by the multi-disciplinary team.
      Currently, ACC might not be suitable for a precision medicine approach according
      to our tests.

PMID- 29444512
TI  - A Phase II Study of Irinotecan for Patients with Previously Treated Small-Cell
      Lung Cancer.
AB  - OBJECTIVE: Chemotherapy with irinotecan plus cisplatin has shown promise in chemo
      naive small-cell lung cancer (SCLC) patients. However, irinotecan treatment for
      relapsed or refractory SCLC has not been adequately evaluated. This phase II
      study evaluated the appropriate treatment schedule of irinotecan as a single
      agent. This study was designed to determine the antitumor activity, toxicity, and
      survival in previously treated SCLC patients. METHODS: Previously treated SCLC
      patients with at least one platinum-based regimen received irinotecan (100 mg/m2)
      on days 1 and 8, every 3 weeks, until disease progression. The assessment of the
      response rate was the primary endpoint. RESULTS: Thirty patients were enrolled,
      with an objective response rate of 41.3% (95% confidence interval [CI] 25.5
      59.3), and a disease control rate of 69%. Median progression-free and overall
      survival was 4.1 months (95% CI, 2.2-5.4) and 10.4 months (95% CI, 8.1-14),
      respectively. The grade 3/4 hematological toxicities were neutropenia (36.7%),
      thrombocytopenia (3.3%), anemia (13.3%), and febrile neutropenia (6.6%). There
      were no grade 4 nonhematological toxicities. Frequent grade 3 nonhematological
      toxicities included diarrhea (10%), anorexia (6.6%), and hyponatremia (6.6%).
      CONCLUSIONS: This phase II study showed a high objective response rate and long
      survival. Irinotecan monotherapy schedule used was well tolerated, and could be
      an active treatment option for these patients.

PMID- 29444514
TI  - Abstracts of the 9th Workshop Probiotics and Prebiotics.

PMID- 29444513
TI  - Comparison of Three Methods Estimating Baseline Creatinine For Acute Kidney
      Injury in Hospitalized Patients: a Multicentre Survey in Third-Level Urban
      Hospitals of China.
AB  - BACKGROUND/AIMS: A lack of baseline serum creatinine (SCr) data leads to
      underestimation of the burden caused by acute kidney injury (AKI) in developing
      countries. The goal of this study was to investigate the effects of various
      baseline SCr analysis methods on the current diagnosis of AKI in hospitalized
      patients. METHODS: Patients with at least one SCr value during their hospital
      stay between January 1, 2011 and December 31, 2012 were retrospectively included
      in the study. The baseline SCr was determined either by the minimum SCr (SCrMIN)
      or the estimated SCr using the MDRD formula (SCrGFR-75). We also used the dynamic
      baseline SCr (SCrdynamic) in accordance with the 7 day/48 hour time window. AKI
      was defined based on the KDIGO SCr criteria. RESULTS: Of 562,733 hospitalized
      patients, 350,458 (62.3%) had at least one SCr determination, and 146,185 (26.0%)
      had repeat SCr tests. AKI was diagnosed in 13,883 (2.5%) patients using the
      SCrMIN, 21,281 (3.8%) using the SCrGFR-75 and 9,288 (1.7%) using the SCrdynamic.
      Compared with the non-AKI patients, AKI patients had a higher in-hospital
      mortality rate regardless of the baseline SCr analysis method. CONCLUSIONS:
      Because of the scarcity of SCr data, imputation of the baseline SCr is necessary
      to remedy the missing data. The detection rate of AKI varies depending on the
      different imputation methods. SCrGFR-75 can identify more AKI cases than the
      other two methods.

PMID- 29444515
TI  - Comprehensive miRNA Analysis of Human Umbilical Cord-Derived Mesenchymal Stromal
      Cells and Extracellular Vesicles.
AB  - BACKGROUND/AIMS: Mesenchymal stromal cells (MSCs) participate in the tissue
      specific repair of many different organs, especially the kidney. Their effects
      are primarily mediated by the paracrine release of factors including
      extracellular vesicles (EVs), which are composed of micro-vesicles and exosomes.
      The corresponding microRNAs (miRNAs) of EVs are considered important for their
      biological functions. METHODS: MSCs were cultured from the human umbilical cord,
      and EVs were isolated from the medium. The expression levels of miRNAs in MSCs
      and EVs were determined by microarray analysis, and gene ontology (GO) was used
      to analyze the functions of their target genes. RESULTS: MSCs and EVs had similar
      miRNA expression profiles, with the exception of a small number of selectively
      enriched miRNAs. GO analysis indicated that, unlike MSCs, the target genes of EV
      enriched miRNAs were associated with calcium channel regulation and cell junction
      activities, which may indicate that MSC and EVs have different regulatory
      properties. Angiogenesis, oxidative stress, and inflammatory signaling pathways
      related to the repair of renal injury were also analyzed, and EV-enriched miRNAs
      targeted genes associated with oxidative stress, T cell activation, and Toll-like
      receptor signaling. The miRNAs enriched in both MSCs and EVs targeted different
      genes in signaling pathways regulating angiogenesis and chemokine release.
      CONCLUSION: MSCs and their EVs shared similar miRNA component, and some
      selectively enriched miRNAs observed in MSCs and EVs may affect different target
      genes through some specific signaling pathways.

PMID- 29444516
TI  - Cardiac Magnetic Resonance Imaging of the Myocardium in Chronic Kidney Disease.
AB  - Early stages of chronic kidney disease (CKD) are often underdiagnosed, while
      their deleterious effects on the cardiovascular (CV) system are already at work.
      Thus, the assessment of early CV damage is of crucial importance in preventing
      major CV events. Myocardial fibrosis is one of the major consequences of
      progressive CKD, as it may lead to reentry arrhythmias and long-term myocardial
      dysfunction predisposing to sudden death and/or congestive heart failure.
      Subclinical myocardial fibrosis, with a potential key role in the development of
      uraemic cardiac disease, can be measured and characterised by appropriate cardiac
      magnetic resonance (CMR) techniques. Fibrosis detection was initially based on
      the contrast agent gadolinium, due to the superiority in sensitivity and accuracy
      of contrast-based methods in fibrosis assessment relative to native techniques.
      However, the severe consequences of gadolinium administration in uraemia
      (nephrogenic systemic fibrosis) have forced practitioners to re-evaluate the
      methodology. In the present overview, we review the possible contrast-based and
      contrast agent-free CMR techniques, including native T1 relaxation time,
      extracellular volume and global longitudinal strain measurement. The review also
      summarises their potential clinical relevance in CKD patients based on recently
      published studies.

PMID- 29444517
TI  - Acetyl-CoA Synthetase 2 Promotes Cell Migration and Invasion of Renal Cell
      Carcinoma by Upregulating Lysosomal-Associated Membrane Protein 1 Expression.
AB  - BACKGROUND/AIMS: Reprogramming energy metabolism is an emerging hallmark of many
      cancers, and this alteration is especially evident in renal cell carcinomas
      (RCCs). However, few studies have been conducted on lipid metabolism. This study
      investigated the function and mechanism of lipid metabolism-related acetyl-CoA
      synthetase 2 (ACSS2) in RCC development, cell migration and invasion. METHODS:
      Quantitative real-time PCR (qRT-PCR) was used to determine the expression of
      ACSS2 in cancer tissue and adjacent tissue. The inhibition of ACSS2 expression
      was achieved by RNA interference, which was confirmed by qRT-PCR and Western
      blotting. Cell proliferation and apoptosis were detected by a CCK8 assay and a
      flow cytometry analysis, respectively. Cell migration and invasion were
      determined by the scratch and transwell assays. Following the knockdown of ACSS2
      expression, the expression of the autophagy-related factor LAMP1 was measured by
      qRT-PCR and Western blotting. RESULTS: Compared to adjacent tissues, ACSS2
      expression was upregulated in RCC cancer tissues and positively correlated with
      metastasis. Inhibition of ACSS2 had no effect on RCC cell proliferation or
      apoptosis. However, decreased ACSS2 expression was found to inhibit RCC cell
      migration and invasion. ACSS2 was determined to promote the expression of LAMP1,
      which can also promote cell migration. This pathway may be considered a potential
      mechanism through which ACSS2 participates in RCC development. CONCLUSION: These
      data suggest that ACSS2 is an important factor for promoting RCC development and
      is essential for cell migration and invasion, which it promotes by increasing the
      expression of LAMP1. Taken together, these findings reveal a potential target for
      the diagnosis and treatment of RCC.

PMID- 29444518
TI  - Effects of Environmental Enrichment on Nicotine Sensitization in Rats Neonatally
      Treated with Quinpirole: Analyses of Glial Cell Line-Derived Neurotrophic Factor
      and Implications towards Schizophrenia.
AB  - The current study analyzed the effects of environmental enrichment versus
      isolation housing on the behavioral sensitization to nicotine in the neonatal
      quinpirole (NQ; dopamine D2-like agonist) model of dopamine D2 receptor
      supersensitivity, a rodent model of schizophrenia. NQ treatment in rats increases
      dopamine D2 receptor sensitivity throughout the animal's lifetime, consistent
      with schizophrenia. Animals were administered NQ (1 mg/kg) or saline (NS) from
      postnatal day (P)1 to P21, weaned, and immediately placed into enriched housing
      or isolated in wire cages throughout the experiment. Rats were behaviorally
      sensitized to nicotine (0.5 mg/kg base) or saline every consecutive day from P38
      to P45, and brain tissue was harvested at P46. Results revealed that neither
      housing condition reduced nicotine sensitization in NQ rats, whereas enrichment
      reduced sensitization to nicotine in NS-treated animals. The nucleus accumbens
      (NAcc) was analyzed for glial cell line-derived neurotrophic factor (GDNF), a
      neurotrophin important in dopamine plasticity. Results were complex, and revealed
      that NAcc GDNF was increased in animals given nicotine, regardless of housing
      condition. Further, enrichment increased GDNF in NQ rats regardless of adolescent
      drug treatment and in NS-treated rats given nicotine, but did not increase GDNF
      in NS-treated controls compared to the isolated housing condition. This study
      demonstrates that environmental experience has a prominent impact on the
      behavioral and the neural plasticity NAcc response to nicotine in adolescence.

PMID- 29444519
TI  - A Cautionary Note: "Real-World" Toxicity of Checkpoint Inhibitors.

PMID- 29444520
TI  - Remodeling of Wall Mechanics and the Myogenic Mechanism of Rat Intramural
      Coronary Arterioles in Response to a Short-Term Daily Exercise Program: Role of
      Endothelial Factors.
AB  - PURPOSE: Exercise elicits early adaptation of coronary vessels enabling the
      coronary circulation to respond adequately to higher flow demands. We
      hypothesized that short-term daily exercise induces biomechanical and functional
      remodeling of the coronary resistance arteries related to pressure. METHODS: Male
      rats were subjected to a progressively increasing 4-week treadmill exercise
      program (over 60 min/day, 1 mph in the final step). In vitro pressure-diameter
      measurements were performed on coronary segments (119 +/- 5 MUm in diameter at 50
      mm Hg) with microarteriography. The magnitude of the myogenic response and
      contribution of endogenous nitric oxide and prostanoid production to the wall
      mechanics and pressure-diameter relationship were assessed. RESULTS: Arterioles
      isolated from exercised ani mals - compared to the sedentary group - had thicker
      walls, increased distensibility, and a decreased elastic modulus as a result of
      reduced wall stress in the low pressure range. The arterioles of exercised rats
      exhibited a more powerful myogenic response and less endogenous vasoconstrictor
      prostanoid modulation at higher pressures, while vasodilator nitric oxide
      modulation of diameter was augmented at low pressures (< 60 mm Hg). CONCLUSIONS:
      A short-term daily exercise program induces remodeling of rat intramural coronary
      arterioles, likely resulting in a greater range of coronary autoregulatory
      function (constrictor and dilator reserves) and more effective protection against
      great changes in intraluminal pressure, contributing thereby to the optimization
      of coronary blood flow during exercise.

PMID- 29444521
TI  - Non-Answered Questions in Patients with Endobronchial Valve Placement for Lung
      Volume Reduction.
AB  - Endoscopic lung volume reduction is a minimally invasive procedure performed to
      reduce the space occupied by the emphysemas' lobes. This procedure has been
      demonstrated to be beneficial for patients with advanced chronic obstructive
      pulmonary disease and severe hyperinflation. The use of endobronchial valves is
      increasing, as well as the number of reports of adverse events. The most common
      complications after the procedure are a pneumothorax, bleeding, infections, the
      need for valve removal, and valve expulsion. We have recently treated a patient
      who achieved immediate left upper lobe atelectasis but developed a pneumothorax
      on the 6th day and near-fatal kinking of the left lower lobe bronchus. This
      patient had asphyctic episodes probably due to a functional left pneumonectomy.
      We should consider this unusual complication in patients undergoing endoscopic
      lung volume reduction whose condition worsens after achieving complete lobar
      atelectasis.

PMID- 29444522
TI  - Psychotic Symptoms and Attitudes toward Medication Mediate the Effect of Insight
      on Personal-Social Functions in Patients with Schizophrenia: One-Year Randomized
      Controlled Trial and Follow-Up.
AB  - AIMS: This study aimed to investigate the mediating pathway of 3 factors
      (psychotic symptoms, attitude toward medication, and cognitive processing speed)
      on the effect of insight on personal-social functioning in patients with
      schizophrenia. METHODS: Chinese inpatients with schizophrenia (n = 168; mean age
      18 +/- 50 years) diagnosed according to the DSM-IV were randomly assigned to
      treatment with antipsychotic medication alone or combined treatment. Positive and
      Negative Syndrome Scale (PANSS), Drug Attitude Inventory (DAI), Assessment of
      Insight (SAI), and Social-Personal Performance Scale (PSPS) scores were evaluated
      at baseline and at 3, 6, and 12 months. Cognitive function was assessed at
      baseline. Multiple mediation analyses were conducted with baseline data, end
      point data, and changes-in-scale scores between baseline and the end point,
      respectively. RESULTS: At baseline and at 12 months, only psychotic symptoms
      mediated the effect of insight on personal-social functioning. For changes-in
      scale scores over the 12-month follow-up, in patients receiving treatment with
      medication alone, the effect of improved insight on improved personal-social
      function was mediated by psychotic symptoms only; in patients receiving a
      combined treatment, the effect of improved insight on improved personal-social
      functioning was mediated by both psychotic symptoms and attitudes toward
      medication, independently. CONCLUSIONS: The link between insight and personal
      social functions is mainly mediated by psychotic symptoms. Psychosocial
      intervention improves the predicting effect of insight on personal-social
      function by improving both the attitude toward medication and psychotic symptoms
      independently.

PMID- 29444523
TI  - A Novel Animal Model of Parkinson's Disease Using Optogenetics: Representation of
      Various Disease Stages by Modulating the Illumination Parameter.
AB  - BACKGROUND: The classic animal model of Parkinson's disease (PD) using neurotoxin
      can only simulate fixed stages of the disease by causing irreversible damage to
      the nigrostriatal system. OBJECTIVES: To develop an optogenetic PD model that can
      modulate the severity of disease by optical stimulation by introducing the
      halorhodopsin (NpHR) gene into the substantia nigra compacta. METHODS: Fifteen
      rats received injections of engineered AAV with NpHR-YFP gene into the substantia
      nigra. They were then subjected to illumination of 590-nm light wavelengths with
      3 optical stimulation conditions, i.e., frequency-width: 5 Hz-10 ms (n = 5), 5 Hz
      100 ms (n = 5), and 50 Hz-10 ms (n = 5). Eleven rats received 6-hydroxydopamine
      injections to establish the conventional PD model. RESULTS: The optogenetic
      models showed characteristic PD manifestations, similar to those of the
      conventional models; the severity of forelimb akinesia correlated with the total
      illumination value (frequency * width). The group with a low illumination value
      (5 Hz-10 ms) was comparable to the conventional partial model whereas the groups
      with high illumination values (5 Hz-100 ms and 50 Hz-10 ms) were similar to the
      conventional complete model. CONCLUSIONS: An optogenetic PD model has the
      advantage of more appropriately representing various PD stages by controlling
      illumination parameters.

PMID- 29444524
TI  - Editorial.

PMID- 29444529
TI  - Endoscopy assistants influence the quality of colonoscopy.
AB  - BACKGROUND:  Colonoscopy performance varies between endoscopists, but little is
      known about the impact of endoscopy assistants on key performance indicators. We
      used a large prospective colonoscopy quality database to perform an exploratory
      study to evaluate differences in selected quality indicators between endoscopy
      assistants. METHODS:  All colonoscopies reported to the Norwegian colonoscopy
      quality assurance register Gastronet can be used to trace individual endoscopy
      assistants. We analyzed key quality indicators (cecum intubation rate, polyp
      detection rate, colonoscopies rated as severely painful, colonoscopies with
      sedation or analgesia, and satisfaction with information) for colonoscopies
      performed between 1 January 2013 and 31 December 2014. Differences between
      individual assistants were analyzed by fitting multivariable logistic regression
      models, with the best performing assistant at each participating hospital as
      reference. All models were adjusted for the endoscopist. RESULTS:  63 endoscopy
      assistants from 12 hospitals assisted in 15 365 colonoscopies. Compared with
      their top performing peers from the same hospital, one assistant was associated
      with cecum intubation failure, four with poor polyp detection, nine with painful
      colonoscopy, 16 with administration of sedation or analgesics during colonoscopy,
      and three with patient dissatisfaction about information given relating to the
      colonoscopy. The number of procedures during the study period or lifetime
      experience as an endoscopy assistant were not associated with any quality
      indicator. CONCLUSION: In this exploratory study, there was little variation on
      important colonoscopy quality indicators between endoscopy assistants. However,
      there were differences among assistants that may be clinically important.
      Endoscopy assistants should be subject to quality surveillance similarly to
      endoscopists.

PMID- 29444530
TI  - Morphine Analgesia Pre-PPCI Is Associated with Prothrombotic State, Reduced
      Spontaneous Reperfusion and Greater Infarct Size.
AB  - : The emergency management of ST-elevation myocardial infarction (STEMI) involves
      treatment with dual-antiplatelet therapy (DAPT) and primary percutaneous coronary
      intervention (PPCI). Pain is generally treated with opiates, which may delay
      gastric transit and reduce DAPT absorption. We sought to assess the effect of
      morphine on reperfusion, infarct size and thrombotic status in 300 patients
      presenting for PPCI. Morphine was given in a non-randomized fashion as required
      by emergency teams en route to the heart attack centre. All patients received
      DAPT and PPCI according to standard care, with optional glycoprotein IIb/IIIa
      inhibitor (GPI) use. Patients were assessed for ST-segment resolution, coronary
      flow, thrombotic status and peak troponin. Patients receiving morphine (n = 218;
      72.7%) experienced less spontaneous ST-segment resolution pre-PPCI, lower rate of
      TIMI 2/3 flow in the infarct-related artery pre-PPCI and higher peak troponin
      level post-PPCI (median [interquartile range]; 1,906 [1,002-4,398] vs. 1,268 [249
      2,920] ng/L; p = 0.016) than those who did not. Patients receiving morphine
      exhibited significantly enhanced platelet reactivity and impaired endogenous
      fibrinolysis on arrival, compared with no-morphine patients. Morphine
      administration was an independent predictor of failure of spontaneous ST-segment
      resolution after adjustment for other variables (odds ratio: 0.26; confidence
      interval: 0.08-0.84; p = 0.025). Among patients receiving GPI, there was no
      difference in pre-PPCI flow or peak troponin according to morphine use,
      suggesting that the adverse effects of morphine relate to delayed DAPT
      absorption, which may be overcome by GPI. Our hypothesis-generating data suggest
      that morphine use in STEMI is associated with enhanced platelet reactivity,
      reduced spontaneous myocardial reperfusion (pre-PPCI) and larger infarct size,
      and these adverse effects may be influenced by GPI use. CLINICAL TRIAL
      REGISTRATION:  URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT02562690.

PMID- 29444531
TI  - ?

PMID- 29444532
TI  - [An across-scales analysis of the voice self-concept questionnaire (FESS)].
AB  - BACKGROUND: The questionnaire for the assessment of the voice selfconcept (FESS)
      contains three sub-scales indicating the personal relation with the own voice.
      The scales address the relationship with one's own voice, the awareness of the
      use of one's own voice, and the perception of the connection between voice and
      emotional changes. A comprehensive approach across the three scales supporting a
      simplified interpretation of the results was still missing. MATERIAL AND METHOD:
      The FESS questionnaire was used in a sample of 536 German teachers. With a
      discrimination analysis, commonalities in the scale characteristics were
      investigated. For a comparative validation with voice health and psychological
      and physiological wellbeing, the Voice Handicap Index (VHI), the questionnaire
      for Work-related Behavior and Experience Patterns (AVEM), and the questionnaire
      for Health-related Quality of Life (SF-12) were additionally collected. RESULTS:
      The analysis provided four different groups of voice self-concept: group 1 with
      healthy values in the voice self-concept and wellbeing scales, group 2 with a low
      voice self-concept and mean wellbeing values, group 3 with a high awareness of
      the voice use and mean wellbeing values and group 4 with low values in all
      scales. CONCLUSION: The results show that a combined approach across all scales
      of the questionnaire for the assessment of the voice self-concept enables a more
      detailed interpretation of the characteristics in the voice self-concept. The
      presented groups provide an applicable use supporting medical diagnoses.

PMID- 29444534
TI  - SMFM 2018: Meeting highlights-Thursday (Podcast).

PMID- 29444533
TI  - Relationship between Blood Glucose Fluctuation and Brain Damage in the
      Hypoglycemia Neonates.
AB  - OBJECTIVE:  To investigate the relationship between blood glucose fluctuation and
      brain damage in the hypoglycemia neonates. STUDY DESIGN:  A retrospective study
      including all neonates hospitalized due to hypoglycemia from September 2013 to
      August 2016 was performed. All the 58 hypoglycemia infants were divided into two
      groups-the brain-damaged group and the nonbrain-damaged group, according to head
      magnetic resonance imaging and/or amplitude-integrated electroencephalogram.
      Relationship between glucose variability and brain damage and whether these
      variation indexes could act as early indicators for hypoglycemic brain damage
      were investigated. RESULTS:  Of the 13 brain-damaged cases, the lowest blood
      glucose (LBG) level was lower, while duration of hypoglycemia was longer compared
      with the 45 nonbrain-damaged cases (p < 0.001). The largest amplitude of glycemic
      excursions, standard deviation of blood glucose, and mean amplitude of glycemic
      excursions (MAGE) of the brain-damaged group were higher (p < 0.001). Under
      receiver-operating characteristic curve, values of area under the curve of MAGE
      were 0.892, duration of hypoglycemia was 0.921, and LBG was 0.109 (p < 0.0001).
      CONCLUSION:  Brain damage of the hypoglycemia neonates relates not only with LBG
      and duration of hypoglycemia but also with the blood glucose variation indexes;
      MAGE and duration of hypoglycemia could act as predictors for brain damage.

PMID- 29444535
TI  - Neonatal Onset of Epilepsy of Infancy with Migrating Focal Seizures Associated
      with a Novel GABRB3 Variant in Monozygotic Twins.
AB  - BACKGROUND:  Recently, a study providing insight into GABRB3 mutational spectrum
      was published (Moller et al 2017). The authors report considerable pleiotropy
      even for single mutations and were not able to identify any genotype-phenotype
      correlations. METHODS:  The proband (twin B) was referred for massively parallel
      sequencing of epilepsy-related gene panel because of hypotonia and neonatal
      seizures. The revealed variant was confirmed with Sanger sequencing in the
      proband and the twin A, and both parents were tested for the presence of the
      variant. RESULTS:  We report a case of epilepsy of infancy with migrating focal
      seizures (EIMFS) of neonatal onset in monozygotic twins with a de novo novel
      GABRB3 variant p.Thr281Ala. The variant has a uniform presentation on an
      identical genomic background. In addition, early seizure-onset epilepsy
      associated with GABRB3 mutation has been until now described only for the
      p.Leu256Gln variant in the GABRB3 (Moller et al 2017, Myers et al 2016) located
      in the transmembrane domain just as the p.Thr281Ala variant described here.
      CONCLUSION:  De novo GABRB3 mutations may cause neonatal-onset EIMFS with early
      onset hypotonia, respiratory distress, and severe developmental delay.

PMID- 29444536
TI  - Optimizing the User Experience: Identifying Opportunities to Improve Use of an
      Inpatient Portal.
AB  - BACKGROUND: Patient portals specifically designed for the inpatient setting have
      significant potential to improve patient care. However, little is known about how
      the users of this technology, the patients, may interact with the inpatient
      portals. As a result, hospitals have limited ability to design approaches that
      support patient use of the portal. OBJECTIVES: This study aims to evaluate the
      user experience associated with an inpatient portal. METHODS: We used a Think
      Aloud protocol to study user interactions with a commercially available inpatient
      portal-MyChart Bedside (MCB). Study participants included 19 English-speaking
      adults over the age of 18 years. In one-on-one sessions, participants narrated
      their experience using the MCB application and completing eight specific tasks.
      Recordings were transcribed and coded into three dimensions of the user
      experience: physical, cognitive, and sociobehavioral. RESULTS: Our analysis of
      the physical experience highlighted the navigational errors and technical
      challenges associated with the use of MCB. We also found that issues associated
      with the cognitive experience included comprehension problems that spurred
      anxiety and uncertainty. Analysis of the sociobehavioral experience suggested
      that users have different learning styles and preferences for learning including
      self-guided, handouts, and in-person training. CONCLUSION: Inpatient portals may
      be an effective tool to improve the patient experience in the hospital. Moreover,
      making this technology available to inpatients may help to foster ongoing use of
      technology across the care continuum. However, deriving the benefits from the
      technology requires appropriate support. We identified multiple opportunities for
      hospital management to intervene. In particular, teaching patients to use the
      application by making a variety of instructional materials available could help
      to reduce several identified barriers to use. Additionally, hospitals should be
      prepared to manage patient anxiety and increased questioning arising from the
      availability of information in the inpatient portal application.

PMID- 29444537
TI  - A Novel Patient Recruitment Strategy: Patient Selection Directly from the
      Community through Linkage to Clinical Data.
AB  - OBJECTIVE: This article presents and describes our methods in developing a novel
      strategy for recruitment of underrepresented, community-based participants, for
      pragmatic research studies leveraging routinely collected electronic health
      record (EHR) data. METHODS: We designed a new approach for recruiting eligible
      patients from the community, while also leveraging affiliated health systems to
      extract clinical data for community participants. The strategy involves methods
      for data collection, linkage, and tracking. In this workflow, potential
      participants are identified in the community and surveyed regarding eligibility.
      These data are then encrypted and deidentified via a hashing algorithm for
      linkage of the community participant back to a record at a clinical site. The
      linkage allows for eligibility verification and automated follow-up. Longitudinal
      data are collected by querying the EHR data and surveying the community
      participant directly. We discuss this strategy within the context of two national
      research projects, a clinical trial and an observational cohort study.
      CONCLUSION: The community-based recruitment strategy is a novel, low-touch,
      clinical trial enrollment method to engage a diverse set of participants. Direct
      outreach to community participants, while utilizing EHR data for clinical
      information and follow-up, allows for efficient recruitment and follow-up
      strategies. This new strategy for recruitment links data reported from community
      participants to clinical data in the EHR and allows for eligibility verification
      and automated follow-up. The workflow has the potential to improve recruitment
      efficiency and engage traditionally underrepresented individuals in research.

PMID- 29444538
TI  - [Effects of judo-specific resistance training on kinetic and electromyographic
      parameters of pulling exercises in judo athletes].
AB  - BACKGROUND: In judo, rapid force production during pulling movements is an
      important component of athletic performance, which is why this capacity needs to
      be specifically exercised in judo. This study aimed at examining the effects of a
      judo-specific resistance training program using a judo ergometer system (PTJ)
      versus a traditional resistance training regime using a partner (PTP) on kinetics
      and muscle activity of judo-specific pulling exercises. METHOD: Twenty-four male
      judo athletes (age: 22 +/- 4 years, training experience: 15 +/- 3 years) were
      randomly assigned to two groups. In a crossover design, the first group completed
      a 4-week PTJ followed by four weeks of PTP (each with three sessions per week).
      The second group conducted PTP prior to PTJ. PTJ and PTP were completed in
      addition to regular training. Before, 4 weeks and 8 weeks after training, tests
      were conducted to assess judo-specific pulling kinetics (i. e. maximal force,
      rate of force development [RFD], mechanical work) and electromyographic (EMG)
      shoulder/trunk muscle activity (i. e. biceps brachii muscle, deltoid muscle,
      trapezius muscle, erector spinae muscle) during pulling movements using a judo
      ergometer as well as unspecific strength tests (i. e. bench-pull, pull-ups).
      RESULTS: The statistical analysis revealed that in both groups ergometer pulling
      kinetics (p <.05, 0.83 <=d<= 1.77) and EMG activity (p <.05; 1.07 <=d<= 2.25)
      were significantly enhanced following 8 weeks of training. In addition,
      significantly larger gains in RFD, mechanical work, and EMG activity (i. e.
      deltoid muscle, erector spinae muscle, trapezius muscle) were found following PTJ
      compared to PTP (p <.05, 1.25 <=d<= 2.79). No significant enhancements were
      observed with the unspecific strength tests. CONCLUSION: Our findings indicate
      that PTJ is superior to PTP regarding training-induced improvements in force
      production and muscle activity during judo-specific pulling exercises.
      Performance enhancements may partly be attributed to neural adaptations. No
      transfer effects on unspecific strength tests were detected following PTJ and
      PTP.

PMID- 29444539
TI  - Relationships between maximal strength of lower limb, anthropometric
      characteristics and fundamental explosive performance in handball players.
AB  - BACKGROUND:  The purpose of this study was to examine relationships between lower
      body muscular strength, anthropometric characteristics and several measures of
      explosive performance in elite team-handball players. METHODS:  22 male elite
      team-handball players (age: 19.1 +/- 1.7 years) were studied during the
      competitive season. Standard anthropometric and body composition measures
      included body mass index, lower limb and thigh muscle volume, and body fat
      percentage. Maximal leg strength was determined by a one-repetition maximum (1
      RM) half back-squat. Vertical jump performance was assessed using a squat jump
      (SJ) and a counter movement jump (CMJ). Repeated shuttle-sprint ability (RSA) was
      tested by 6 (2 * 15 m) shuttle sprints with 20 s of active recovery intervals.
      The best time in a single shuttle sprint (30m; RSAbest), fastest total time
      (RSATT) and RSA test performance decrement (RSAdec) were recorded. Agility was
      measured using a modified T-half test (MAT). Throwing velocities of jump shooting
      and 3-step throwing were recorded by digital video camera. RESULTS:  The
      explained variance of 1-RM half-back-squats ranged from 0.2 % (RSA% Fatigue
      Index) to 70.1 % (CMJ). Four out of 8 variables (RSA Best Time, CMJ, SJ, throwing
      velocity of jump shoot) demonstrated an r2 > 0.5. Jump performances seemed
      closely related to 1-RM half-back-squats. Furthermore, 1-RM half-back-squats were
      positively correlated with leg and thigh muscle volumes (r = 0.652, r = 0.768).
      CONCLUSION:  The anthropometric characteristics and some physical performance
      tests are closely related to the maximal strength performance of handball
      players. Coaches should focus on maximal strength training programs for the lower
      limbs when seeking improvements in the throwing velocity and jump performance of
      handball players.

PMID- 29444540
TI  - The Impact of Computed Tomography on Decision Making in Tibial Plateau Fractures.
AB  - Schatzker introduced one of the most used classification systems for tibial
      plateau fractures, based on plain radiographs. Computed tomography brought to
      attention the importance of coronal plane-oriented fractures. The goal of our
      study was to determine if the addition of computed tomography would affect the
      decision making of surgeons who usually use the Schatzker classification to
      assess tibial plateau fractures. Image studies of 70 patients who sustained
      tibial plateau fractures were uploaded to a dedicated homepage. Every patient was
      linked to a folder which contained two radiographic projections (anteroposterior
      and lateral), three interactive videos of computed tomography (axial, sagittal,
      and coronal), and eight pictures depicting tridimensional reconstructions of the
      tibial plateau. Ten attending orthopaedic surgeons, who were blinded to the
      cases, were granted access to the homepage and assessed each set of images in two
      different rounds, separated to each other by an interval of 2 weeks. Each case
      was evaluated in three steps, where surgeons had access, respectively to
      radiographs, two-dimensional videos of computed tomography, and three-dimensional
      reconstruction images. After every step, surgeons were asked to present how would
      they classify the case using the Schatzker system and which surgical approaches
      would be appropriate. We evaluated the inter- and intraobserver reliability of
      the Schatzker classification using the Kappa concordance coefficient, as well as
      the impact of computed tomography in the decision making regarding the surgical
      approach for each case, by using the chi-square test and likelihood ratio. The
      interobserver concordance kappa coefficients after each assessment step were,
      respectively, 0.58, 0.62, and 0.64. For the intraobserver analysis, the
      coefficients were, respectively, 0.76, 0.75, and 0.78. Computed tomography
      changed the surgical approach selection for the types II, V, and VI of Schatzker
      (p < 0.01). The addition of computed tomography scans to plain radiographs
      improved the interobserver reliability of Schatzker classification. Computed
      tomography had a statistically significant impact in the selection of surgical
      approaches for the lateral tibial plateau.

PMID- 29444541
TI  - Functional Regions of the Medial Patellofemoral Ligament.
AB  - The purpose of this study was to explore the anatomy and discuss functional
      regions of the medial patellofemoral ligament (MPFL). Twelve fresh-frozen knees
      specimens were dissected. All medial surfaces of knees were intact and did not
      have indication of injury. General feature of the MPFL were observed. All
      anatomical landmarks were carefully identified and marked. The length of the two
      functional regions were conducted and recorded. All data were obtained,
      described, and analyzed in the form of mean +/- standard deviation. The MPFL was
      found in all specimens we dissected. Closed to the patellar insertion, it adheres
      to the deep surface of the vastus medialis obliquus (VMO). Due to the VMO, the
      MPFL is divided into two functional regions: overlap region and nonoverlap
      region. Anatomically, the overlap region and nonoverlap region of 25.43 +/- 2.0
      and 44.85 +/- 3.04 mm, the width of VMO insertion is 13.94 +/- 2.03 mm, and the
      width of patellar insertion is 22.91 +/- 3.46 mm. We divide the MPFL into two
      anatomical functional regions, demarcated by the meshing points of fibers between
      the MPFL and VMO: overlap region and nonoverlap region. This finding provides the
      theoretical foundation for the treatment of the MPFL injury and shed lights on
      the future researches.

PMID- 29444542
TI  - Kinematically Aligned Total Knee Arthroplasty or Mechanically Aligned Total Knee
      Arthroplasty.
AB  - Kinematically aligned total knee arthroplasty (KATKA) was developed to more
      anatomically align the knee prosthesis to restore the native alignment of the
      knee and promote physiological kinematics. Even though there are concerns with
      implant survival, and follow-up at 10 years or more after KATKA has not been
      reported, there is a negligible incidence of failure of a tibial component at 2
      to 9 years. Early clinical results with this technique are encouraging and
      demonstrate better functional outcomes compared with mechanically aligned TKA
      (MATKA). The purpose of this study is to perform a systematic review and meta
      analysis of the literature to determine whether there are any clinical
      differences between KATKA and MATKA. The authors conducted a systematic review of
      the English literature. Five randomized controlled trials (RCTs) which compared
      clinical outcomes of KATKA and MATKA were finally included. Four RCTs used
      patient-specific instrument, and one RCT used navigation. Data were extracted and
      meta-analysis was conducted. KATKA patients had better outcomes: Mean difference
      between KATKA and MATKA and p-value are presented in brackets after each
      variable: the Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC) (-12.5; p < 0.0001), Oxford Knee Score (OKS) (2.3; p = 0.030), combined
      Knee Society Score (C-KSS) (13.1; p < 0.0001), Knee Function Score (KFS) (6.4; p
      = 0.0070), and postoperative range of motion (ROM) (4.1 degrees ; p = 0.0010).
      There was no significant difference concerning the complication rates which
      needed reoperations or revision surgery (odds ratio, 1.01; p = 0.99). KATKA
      components had a more femoral valgus (-1.8 degrees ; p < 0.0001), more tibial
      varus (1.2 degrees ; p = 0.0001), and more tibial slope (1.2 degrees ; p =
      0.0001), all being statistically significantly different. Better clinical
      outcomes were obtained in KATKA and component placement in KATKA is significantly
      different from that in MATKA. There was no increase of patients with poor
      clinical results due to implant position especially for varus placement of tibial
      component. This systematic review of five RCTs suggests that KATKA is of
      potential alternative method to MATKA since the risk of revision for tibial
      loosening is negligible compared with MATKA for the same follow-up period.

PMID- 29444543
TI  - Posterolateral Corner Reconstruction Using the Anatomical Two-Tailed Graft
      Technique: Clinical Outcomes in the Multiligament Injured Knee.
AB  - Injury to the posterolateral corner (PLC) of the knee can lead to both varus and
      rotational instability. Multiple PLC reconstruction techniques have been
      described, including one-tailed graft (fibula-based constructs) or two-tailed
      graft (combined fibula- and tibia-based constructs). The purpose of our study was
      to evaluate the clinical outcomes of anatomical two-tailed graft reconstruction
      of the PLC in the setting of multiligament knee injuries (MKLIs) with grade III
      varus instability. Patients were identified through a prospective MLKI database
      between 2004 and 2013. Patients who received fibular collateral ligament and PLC
      reconstructions using a two-tailed graft and had a minimum follow-up of 2 years
      were included. Patients were assessed for clinical laxity grade, range of motion,
      and functional outcomes using Lysholm and International Knee Documentation
      Committee (IKDC) scores. Twenty patients (16 male, 4 female) with a mean age of
      30.7 (range: 16-52) and a mean follow-up of 52.2 months (range: 24-93 months)
      were included. Knee dislocation (KD) grades included: 4 KD-1, 10 KD 3-L, 5 KD-4,
      and 1 KD-5. No patients had isolated PLC injuries. Mean IKDC and Lysholm score
      were 73.1 +/- 25.8 and 78 +/- 26, respectively. Mean range of motion was -1.1 to
      122.8. In full extension, two patients (10%) had grade 1 laxity to varus stress.
      In 30 degrees of knee flexion, five (25%) patients had grade 1 laxity, and two
      (10%) had grade 2 laxity. Anatomical two-tailed PLC reconstruction can reliably
      restore varus stability when performed on patients with MLKIs and type C
      posterolateral instability with hyperextension external rotation recurvatum
      deformity. Satisfactory functional outcome scores were achieved in the majority
      of patients. This study supports the use of an anatomical two-tailed PLC
      reconstruction in the multiligament injured knee. The level of evidence is IV,
      case series.

PMID- 29444544
TI  - Uridine 5'diphospho-glucuronosyltransferase 1A expression as an independent
      prognosticator in urothelial carcinoma of the upper urinary tract.
AB  - OBJECTIVE: To determine the expression status of uridine 5'diphospho
      glucuronosyltransferase 1A, a major phase II drug metabolism enzyme, in upper
      urinary tract urothelial carcinoma, as well as to assess its prognostic
      significance. METHODS: We immunohistochemically stained for uridine 5'diphospho
      glucuronosyltransferase 1A in tissue microarray consisting of 99 upper urinary
      tract urothelial carcinoma samples and paired non-neoplastic urothelial tissues.
      We also assessed the effect of uridine 5'diphospho-glucuronosyltransferase 1A
      knockdown on urothelial cancer cell growth. RESULTS: Uridine 5'diphospho
      glucuronosyltransferase 1A was positive in 92.9% (27.3% weak [1+], 37.4% moderate
      [2+], 28.3% strong [3+]) of tumors, which was significantly (P < 0.001) lower
      than in benign urothelial tissues (98.8%; 3.5% 1+, 18.8% 2+, 76.4% 3+). All 37
      (100%) non-muscle-invasive versus 55 (88.7%) of 62 muscle-invasive tumors (P =
      0.043) were immunoreactive for uridine 5'diphospho-glucuronosyltransferase 1A.
      The rates of moderate-to-strong uridine 5'diphospho-glucuronosyltransferase 1A
      expression and its positivity were also strongly associated with the absence of
      concomitant carcinoma in situ (P = 0.034) and lymphovascular invasion (P =
      0.016), respectively. However, there were no statistically significant
      associations between uridine 5'diphospho-glucuronosyltransferase 1A expression
      and tumor grade or pN/M status. Uridine 5'diphospho-glucuronosyltransferase 1A
      loss in M0 tumors was strongly associated with lower progression-free survival (P
      < 0.001) and cancer-specific survival (P < 0.001) rates. Multivariate analysis
      further identified a strong correlation of uridine 5'diphospho
      glucuronosyltransferase 1A positivity with reduced cancer-specific mortality
      (hazard ratio 0.28, P = 0.018). Meanwhile, uridine 5'diphospho
      glucuronosyltransferase 1A knockdown in urothelial cancer cells resulted in
      significant increases in their viability and migration. CONCLUSIONS: These
      results suggest a preventive role of uridine 5'diphospho-glucuronosyltransferase
      1A signals in the development and progression of upper urinary tract urothelial
      carcinoma. Loss of uridine 5'diphospho-glucuronosyltransferase 1A expression
      might serve as an independent predictor of poor prognosis in patients with upper
      urinary tract urothelial carcinoma.

PMID- 29444545
TI  - Bretschneider and del Nido solutions: Are they safe for coronary artery bypass
      grafting? If so, how should we use them?
AB  - A variety of cardioplegic solutions are being used widely today to arrest the
      heart during coronary artery bypass grafting (CABG) and other cardiac operations.
      To minimize interruptions during the surgery for intermittent dosing of the
      cardioplegia and to facilitate less invasive cardiac procedures, single-shot
      solutions, including Bretschneider and del Nido solutions, have been introduced.
      This review examines the evidence regarding the safety and efficacy of
      Bretschneider and del Nido cardioplegia during CABG. The findings support their
      use in routine low-risk CABG, but finds insufficient evidence to support their
      safety in high-risk surgeries.

PMID- 29444546
TI  - Simultaneous small-sample comparisons in longitudinal or multi-endpoint trials
      using multiple marginal models.
AB  - Simultaneous inference in longitudinal, repeated-measures, and multi-endpoint
      designs can be onerous, especially when trying to find a reasonable joint model
      from which the interesting effects and covariances are estimated. A novel
      statistical approach known as multiple marginal models greatly simplifies the
      modelling process: the core idea is to "marginalise" the problem and fit multiple
      small models to different portions of the data, and then estimate the overall
      covariance matrix in a subsequent, separate step. Using these estimates
      guarantees strong control of the family-wise error rate, however only
      asymptotically. In this paper, we show how to make the approach also applicable
      to small-sample data problems. Specifically, we discuss the computation of
      adjusted P values and simultaneous confidence bounds for comparisons of
      randomised treatment groups as well as for levels of a nonrandomised factor such
      as multiple endpoints, repeated measures, or a series of points in time or space.
      We illustrate the practical use of the method with a data example.

PMID- 29444547
TI  - Laparoscopic surgery with urinary tract reconstruction and bowel endometriosis
      resection for deep infiltrating endometriosis.
AB  - Deep infiltrating endometriosis (DIE) is the most severe form of endometriosis.
      It causes chronic pelvic pain, severe dysmenorrhea, deep dyspareunia, dyschezia,
      and dysuria, markedly impairing the quality of life of women of reproductive age.
      A number of randomized controlled trials on surgical and medical treatments to
      reduce the pain associated with endometriosis have been reported, but few have
      focused on this in DIE. DIE causes not only pain but also functional invasion to
      the urinary organs and bowel, such as hydronephrosis and bowel stenosis. In
      addition to DIE resection, surgical treatment involves adhesion separation as
      well as resection and reconstruction of the urinary organs and bowel; high-level
      skills are required. The severity of DIE should be evaluated preoperatively as
      accurately as possible. Using ENZIAN in conjunction with the AFS (The revised
      American Fertility Society classification of endometriosis) classification makes
      a more detailed assessment of DIE possible. The operative procedures used for
      laparoscopic resection of urinary DIE and reconstruction of the urinary organs
      are chosen based on the type of lesion (intrinsic/extrinsic) and length of
      stenosis. In addition to ureteroneocystostomy, the psoas bladder hitch and Boari
      bladder flap procedures are applied when necessary to extend the urinary tract.
      Bowel resection for bowel endometriosis is classified into classic segmental
      resection and conservative approaches (shaving/discoid). When these procedures
      are employed, it is advisable to work in consultation with urologists and
      gastroenterologists and to inform the patients of the associated risks and
      outcomes. Furthermore, postoperative medication is essential because it is
      difficult to conduct repeated surgeries.

PMID- 29444548
TI  - Tribute to Professor Malcolm Bourne.

PMID- 29444549
TI  - Body weight change is unpredictable after total thyroidectomy.
AB  - BACKGROUND: There is a common perception that total thyroidectomy causes weight
      gain beyond expected age-related changes, even when thyroid replacement therapy
      induces a euthyroid state. The aim of this study was to determine whether
      patients who underwent total thyroidectomy for a wide spectrum of conditions
      experienced weight gain following surgery. METHODS: We retrospectively studied
      107 consecutive total thyroidectomy patients treated between January 2013 and
      June 2014. Medical records were reviewed to determine underlying pathology,
      thyroid status, use of antithyroid drugs and preoperative weight. Follow-up data
      were obtained from 79 patients at least 10 months post-operatively to determine
      current weight, the type of clinician managing thyroid replacement therapy and
      patient satisfaction with post-thyroidectomy management. RESULTS: The cohort was
      73% female, with a mean age of 55.8 +/- 15.7 years and a mean preoperative weight
      of 78.8 +/- 17.5 kg. Commonest pathologies were multinodular goitre, Graves'
      disease, thyroid cancer and Hashimoto's thyroiditis. Preoperatively, 63.2% of
      patients were hyperthyroid. Mean weight change at follow-up was a non-significant
      increase of 0.06 +/- 6.9 kg (P = 0.094). Weight change was not significant
      regardless of preoperative thyroid function status. This study did not
      demonstrate any significant differences in clinical characteristics (including
      post-operative thyroid-stimulating hormone) between the group with >2% weight
      gain and those who did not. CONCLUSIONS: This study did not reveal significant
      weight gain following thyroidectomy for a wide spectrum of pathologies.
      Specifically, preoperative hyperthyroidism, female gender and use of antithyroid
      medications do not predict weight gain after thyroid surgery.

PMID- 29444550
TI  - Non-invasive assessment of kidney allograft fibrosis with shear wave
      elastography: A radiological-pathological correlation analysis.
AB  - OBJECTIVES: To evaluate the use of shear wave elastography in assessment of
      kidney allograft tubulointerstitial fibrosis. METHODS: Shear wave elastography
      assessment was carried out by two independent operators in kidney transplant
      recipients who underwent allograft biopsy for clinical indications (i.e. rising
      creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by
      the same pathologist according to the 2013 Banff Classification. RESULTS: A total
      of 40 elastography scans were carried out (median creatinine 172.5 MUmol/L
      [interquartile range 133.8-281.8 MUmol/L]). Median tissue stiffness at the cortex
      (22.6 kPa [interquartile range 18.8-25.7 kPa] vs 22.3 kPa [interquartile range
      19.0-26.5 kPa], P = 0.70) and medulla (15.0 kPa [interquartile range 13.7-18.0
      kPa] vs 15.6 kPa [interquartile range 14.4-18.2 kPa]) showed no significant
      differences between the two observers. Interobserver agreement was satisfactory
      (intraclass correlation coefficient of the cortex 0.84, 95% CI 0.70-0.92 and
      intraclass correlation coefficient of the medulla 0.88, 95% CI 0.78-0.94). The
      areas under the receiver operating characteristic curves for detection of
      tubulointerstitial fibrosis were estimated to be 0.75 (95% CI 0.61-0.89), 0.85
      (95% CI 0.75-0.95) and 0.65 (95% CI 0.53-0.78) for cortical, medullary tissue
      stiffness and serum creatinine, respectively. CONCLUSIONS: Shear wave
      elastography can be used as a non-invasive tool to evaluate kidney allograft
      fibrosis with reasonable interobserver agreement and superior test performance to
      serum creatinine in detecting early tubulointerstitial fibrosis.

PMID- 29444551
TI  - Spontaneous rupture of an aortocoronary saphenous vein graft.

PMID- 29444552
TI  - Optometry-facilitated teleophthalmology: an audit of the first year in Western
      Australia.
AB  - BACKGROUND: Lions Outback Vision has run a state-wide teleophthalmology service
      since 2011. In September 2015 the Australian federal government introduced a
      Medicare reimbursement for optometry-facilitated teleophthalmology consultations
      under specific circumstances. This audit demonstrates the first 12 months
      experience with this scheme. We aim to provide practical insights for others
      looking to embed a telemedicine program as part of delivering outreach clinical
      services. METHODS: A 12-month retrospective audit was performed between September
      2015 and August 2016, inclusive. A research officer used a specifically designed
      data extraction tool to record information from all teleophthalmology
      consultations performed in the time period. The primary outcome was the diagnosis
      at the end of the teleophthalmology consultation. Secondary outcome measures
      included the number of teleconsultations, cataract surgery rate, remoteness area
      of patients referred and imaging accompanying the referral. RESULTS: In the 12
      month period, 709 patients were referred resulting in 683 teleophthalmology
      teleconsultations. Cataract was the most frequent diagnosis (n = 287, 42.7 per
      cent), followed by glaucoma (n = 77, 11 per cent), age-related macular
      degeneration (n = 30, 4.4 per cent) and diabetic retinopathy (n = 26, 3.8 per
      cent). Of those who had teleconsultations, 98.6 per cent were from Outer
      Regional, Remote or Very Remote Australia. One or more accompanying images or
      investigations were part of 349 (49 per cent) teleconsultations, most commonly
      optical coherence tomography (215, 30 per cent) and fundus photography (148, 21
      per cent). Face-to-face consultations were undertaken at an outreach clinic in 23
      (3.4 per cent) cases, to determine the diagnosis. There were no statistically
      significant factors associated with attendance at teleophthalmology consultation,
      or for successfully undergoing cataract surgery. CONCLUSION: Teleophthalmology is
      a valuable adjunct to regional outreach ophthalmology services, providing
      patients with increased access to specialist care for a wide range of ophthalmic
      conditions, and more efficient access to surgical care.

PMID- 29444554
TI  - Dynamic Nanomaterials Phenomena Investigated with in Situ Transmission Electron
      Microscopy: A Nano Letters Virtual Issue.

PMID- 29444553
TI  - Evaluation of biomarkers for treatment selection using individual participant
      data from multiple clinical trials.
AB  - Biomarkers that predict treatment effects may be used to guide treatment
      decisions, thus improving patient outcomes. A meta-analysis of individual
      participant data (IPD) is potentially more powerful than a single-study data
      analysis in evaluating markers for treatment selection. Our study was motivated
      by the IPD that were collected from 2 randomized controlled trials of
      hypertension and preeclampsia among pregnant women to evaluate the effect of
      labor induction over expectant management of the pregnancy in preventing
      progression to severe maternal disease. The existing literature on statistical
      methods for biomarker evaluation in IPD meta-analysis have evaluated a marker's
      performance in terms of its ability to predict risk of disease outcome, which do
      not directly apply to the treatment selection problem. In this study, we propose
      a statistical framework for evaluating a marker for treatment selection given IPD
      from a small number of individual clinical trials. We derive marker-based
      treatment rules by minimizing the average expected outcome across studies. The
      application of the proposed methods to the IPD from 2 studies in women with
      hypertension in pregnancy is presented.

PMID- 29444555
TI  - WITHDRAWAL: Significant effect of anti-tyrosine kinase inhibitor (Gefitinib) on
      overall survival of the Glioblastoma (GBM) patients in the backdrop of mutational
      status of EGFR and PTEN genes.
AB  - The article by Sajad ARIF, Arshad PANDITH, Rehana TABASUM, Altaf RAMZAN,
      Sarabjeet SINGH, Mushtaq SIDDIQI, Abdul BHAT entitled "SIGNIFICANT EFFECT OF ANTI
      TYROSINE KINASE INHIBITOR (GEFITINIB) ON OVERALL SURVIVAL OF THE GLIOBLASTOMA
      (GBM) PATIENTS IN THE BACKDROP OF MUTATIONAL STATUS OF EGFR AND PTEN GENES" was
      published ahead of print in the Journal of Neurosurgical Sciences on February 13,
      2018. As corresponding author of the article, Dr. Sajad ARIF declares that he and
      his group submitted the same manuscript to two different journals simultaneously
      (Journal of Neurosurgical Sciences and Asian J Neurosurg), with subsequent
      redundant publications.The authors confirm their responsibility and ask for the
      Epub ahead of print publication of their paper in the Journal of Neurosurgical
      Sciences to be withdrawn.The authors deeply regret this circumstance and
      apologize for this misconduct to the Journal of Neurosurgical Sciences, to the
      Asian J Neurosurg, as well as to the readers of the journals.The corresponding
      author, Sajad ARIF

PMID- 29444556
TI  - Transvenous embolization of brain arteriovenous malformations: a systematic
      review and meta-analysis.
AB  - INTRODUCTION: The safety and efficacy of transvenous embolization of brain
      arteriovenous malformations (AVM) remains relatively poorly understood. We
      performed a systematic review of the literature to determine outcomes of
      transvenous embolization of brain AVMs. EVIDENCE ACQUISITION: Data Sources
      include Ovid MEDLINE, Ovid EMBASE and the Web of Science. All case series with
      >=4 patients receiving transvenous embolization of brain AVMs published through
      September 2017 were included. EVIDENCE SYNTHESIS: A total of 8 series with 66
      patients were included. All-cause mortality rate was 6.0% (95%CI=0.0%-11.0%).
      There were no cases of treatment related mortality. Overall good functional
      outcome rates were 89.0% (95%CI=82.0%-96.0%). Complete occlusion rates were 96.0%
      (95%CI=91.0%-100.0%). Technical complications rates were 8.0% (95%CI=2.0%-14.0%).
      Additional treatment rates were 6.0% (95%CI=0.0%-11.0%). CONCLUSIONS: Patients
      receiving transvenous embolization of AVMs experience good long- term clinical
      outcomes in nearly 90% of highly selected cases. Further large case series are
      needed to confirm the result.

PMID- 29444557
TI  - Limits of the endoscopic transnasal transtubercular approach.
AB  - INTRODUCTION: The endoscopic transnasal trans-sphenoidal transtubercular approach
      has become a standard alternative approach to neurosurgical transcranial routes
      for lesions of the anterior skull base in particular pathologies of the anterior
      tubercle, sphenoid plane, and midline lesions up to the interpeduncular cistern.
      For both the endoscopic and the transcranial approach indications must strictly
      be evaluated and tailored to the patients' morphology and condition. The purpose
      of this review was to evaluate the evidence in literature of the limitations of
      the endoscopic transtubercular approach. EVIDENCE ACQUISITION: A PubMed/Medline
      search was conducted in January 2018 entering following keywords. Upon initial
      screening 7 papers were included in this review. There are several other papers
      describing the endoscopic transtubercular approach (ETTA). We tried to list the
      limitation factors according to the actual existing literature as cited. EVIDENCE
      SYNTHESIS: The main limiting factors are laterally extending lesions in relation
      to the optic canal and vascular encasement and/or unfavorable tumor tissue
      consistency. CONCLUSIONS: The ETTA is considered as a high level transnasal
      endoscopic extended skull base approach and requires excellent training, skills
      and experience.

PMID- 29444558
TI  - Limitations of the endoscopic endonasal transcribriform approach.
AB  - The endoscopic endonasal transcribriform approach (EETA) has become a useful
      strategy in the treatment of various anterior skull base pathologies, including
      meningoencephaloceles, olfactory groove meningiomas, schwannomas,
      esthesioneuroblastomas, and other sinonasal malignancies. However, not all
      pathologies are optimally treated through this approach due to tumor size, extent
      of the lesion, vascular involvement, and the presence of intact olfaction. One
      must be prepared to use a transcranial approach if the EETA is not favorable. In
      some patients, a combined approach (transcranial-EETA) may be needed in
      appropriate cases. Therefore, patient selection is paramount for achieving a
      successful result with avoidance of complications. For certain tumors, the
      limitations of the EETA may result in lower rates of gross-total resection,
      higher rates of cerebrospinal fluid leakage, postoperative impairment of
      olfaction, and higher complication rates. In this paper, we discuss the
      limitations of the EETA when considering approach selection to treat anterior
      skull base lesions.

PMID- 29444559
TI  - Concurrent Alzheimer's pathology in patients with clinical normal pressure
      hydrocephalus.
AB  - BACKGROUND: Patients with normal pressure hydrocephalus (NPH) and Alzheimer's
      dementia (AD) can often present with similar symptoms. NPH remains a clinical
      diagnosis and there are reported shared underlying dynamics of cerebrospinal
      fluid (CSF) flow and histopathology with patients with biopsy-proven AD. METHODS:
      This is a review on the histopathology and cerebrospinal fluid dynamics of both
      NPH and AD. In a prior study at the University of Virginia, the authors reviewed
      patients over a 15 year period who were shunted for a preoperative diagnosis of
      NPH. Of these patients, 74% received high volume lumbar puncture and at the time
      of surgery, 159 total biopsies were performed on 113 patients with 46 repeat
      biopsies. The results of high-volume lumbar punctures, cortical brain biopsies,
      and clinical outcomes were compared between patients with NPH and those found to
      have Alzheimer's pathology. RESULTS: As many as 24% of patients with clinical
      diagnosis of NPH may demonstrate concomitant Alzheimer's dementia based on
      histopathological biopsy performed at the time of shunt placement. In patients in
      whom a CSF shunt was placed and biopsy obtained, 19% of patients demonstrated
      histopathologiy consistent with CERAD diagnosis of AD. However, more than half
      (53%) of all patients demonstrated some degree of neuritic plaque development,
      while 14% and 9% demonstrated evidence of neurofibrillary tangles and amyloid
      angiopathy, respectively. The improved clinical response seen with HVLP was not
      sustained following shunt insertion; 45% of NPH patients with positive response
      to HVLP improved following shunt placement compared to just 18% of concurrent NPH
      and AD patients (p = 0.0136). CONCLUSIONS: There is a high prevalence of AD in
      patients who are shunted for a clinical diagnosis of NPH. The presenting symptoms
      of NPH and AD may be very similar and the significant difference in
      histopathology is what separates the two disease processes. There may be
      temporary relief with restoring cerebrospinal fluid flow but the presence of
      underlying neurodegenerative changes more directly correlates with long-term
      outcomes. There may also be a direct correlation between altered CSF dynamics in
      both the metabolic clearance and the development of dementia.

PMID- 29444560
TI  - Cohort studies, trials, and tribulations: systematic review and an evidence-based
      approach to arteriovenous malformation treatment.
AB  - INTRODUCTION: There is uncertainty as to the best management of arteriovenous
      malformations of the brain (bAVM). However, the Spetzler-Martin grade (SMG) has
      been validated as an effective determinant of surgical risks. We performed a
      systematic review for the best evidence regarding the management of bAVM for
      series that incorporate an analysis based upon SMG. EVIDENCE ACQUISITION:
      Medline, Embase, Scopus and Cochrane databases were searched for series between
      January 2000 and January 2018, with a minimum of 100 cases and that incorporated
      SMG stratification. From this primary search, series were selected for analysis
      that dichotomized outcomes at modified Rankin Scale (mRS) scores between 1 and 2
      due to complications of treatment or reported favorable outcome (FO) (i.e.
      complete occlusion, no neurological deterioration and no post treatment
      hemorrhage). Case series that used a subset of the population other than SMG or
      had a prior history of hemorrhage were excluded. The series finally analyzed were
      explored for outcomes that reported: complications of treatment that led to a new
      permanent neurological deficit with mRS score >1 (adverse outcome); post
      treatment hemorrhage; occlusion rate; and FO. A comparison of treatment outcomes
      was made when more than one modality of treatment (surgery, radiosurgery,
      embolization or multiple treatment modalities) could be examined with results for
      specific Spetzler-Ponce class (SPC) A (i.e. SMG I and II), B (i.e. SMG III) or C
      (i.e. SMG IV and V). EVIDENCE SYNTHESIS: The primary search produced 116 papers.
      After reviewing each publication and eliminating papers that had patient outcomes
      duplicated, 11 publications met the criteria for analysis (including: 5
      exclusively surgery; 4 exclusively radiosurgery; 1 exclusively endovascular; and,
      1 multi-modality). The following outcome comparisons analyzed were significant.
      For SPC A and B bAVM, there was a significantly higher rate of FO following
      treatment by surgery (98.6%; 95% CI: 97.5-99.2% and 76.4%; 95% CI: 70.0-81.7%,
      respectively) than radiosurgery (70.8%; 95% CI: 66.8-74.6% and 61.0%; 95% CI:
      56.0-65.8%, respectively)(P<0.01). For SPC A and B bAVM, there were significantly
      fewer unobliterated bAVM following treatment by surgery (0.5%; 95% CI: 0.2-1.4%
      and 3.0%; 95% CI: 1.4-5.8%, respectively) than radiosurgery (23.9%; 95% CI: 20.4
      27.8% and 30.9%; 95% CI: 27.9-34.0%, respectively) or embolization (7.6%; 95% CI:
      4.3-12.9% SPC A) (P<0.01). Adverse outcomes from treatment were significantly
      higher for surgery (15.6%; 95% CI: 11.8-20.0%) than radiosurgery (3.3%; 95% CI:
      2.3-4.8%) for SPC B (P<0.01) but not SPC A bAVM. No analysis of SPC C was
      possible. CONCLUSIONS: Surgery remains, in general, the best choice for treating
      SPC A bAVM. For SPC B bAVM the decision as to best treatment should hinge on the
      likelihood of obliteration by radiosurgery. In cases where obliteration rate is
      expected to be high, radiosurgery should be the preferred treatment. There is
      insufficient information to make a recommendation from this analysis with regards
      the role of embolization for cure. There is no satisfactory standardized
      treatment for SPC C bAVM and treatment must remain individualized.

PMID- 29444561
TI  - Committed to be fit. The value of preoperative care in the perioperative medicine
      era.
AB  - In the era of perioperative medicine, important advances have been made in the
      perioperative care of patients, usually within those known as enhanced recovery
      after surgery (ERAS) protocols. These have led to a decrease in postoperative
      complications and the duration of hospital stays; however, there is still a lack
      of preoperative care, which could make perioperative medicine more prominent.
      Elderly patients, malnourished, anemic and ones with a low physical function
      before surgery are likely to have sub-optimal recovery from surgery. More
      importantly, a low functional reserve, together with the inherent physiological
      stress of surgery, reduces the functional capacity of patients in the
      postoperative period, meaning that they will not reach their preoperative
      functional capacity. It is well established that both preoperative malnutrition
      and anemia worsen surgical results, however, for various reasons, their
      preoperative optimization is complex. Additionally, both are related to the
      functional capacity of patients. During the last years, prehabilitation has been
      incorporated into ERAS protocols. Prehabilitation consists of exercise training
      and nutritional and psychological support, which increases the physiological
      reserve before surgical stress. The integration of exercise, adequate nutrition,
      anemia correction and psycho-social components, with multi-modal optimization in
      the preoperative period leads to an improvement in the functional capacity of the
      patients undergoing surgery, with the consequent improvement in terms of
      outcomes. The present article discusses specific aspects of preoperative care
      which are not well defined in the ERAS protocols and which represent fundamental
      shifts in surgical practice, including preoperative nutrition, management of
      preoperative anemia and prehabilitation.

PMID- 29444562
TI  - Fluid resuscitation during early sepsis: a need for individualization.
AB  - The prognosis of septic shock is tightly linked to the earliness of both
      appropriate antibiotic therapy and early hemodynamic resuscitation. This latter
      is essentially based on fluid and vasopressors administration. The step-by-step
      strategy, called "early goal-directed therapy" (EGDT) developed in 2001 and
      endorsed by the Surviving Sepsis Campaign (SSC) between 2004 and 2016 is no
      longer recommended. Indeed, recent multicenter randomized clinical trials showed
      no reduction in all-cause mortality, duration of organ support and in-hospital
      length of stay with EGDT in comparison with standard care. The most recent SCC
      guidelines have dropped the original EGDT by deleting the central venous pressure
      and the central venous oxygen saturation from the recommendations. Dynamic
      variables of fluid responsiveness are now recommended to be used after an initial
      fluid infusion of a fixed volume (30 mL/kg) during the first three hours of
      resuscitation. However, this approach is also questionable due to the lack of
      individualization at the early and crucial phase of resuscitation. In this
      review, we propose a more personalized approach for the early and later phases of
      fluid resuscitation during sepsis.

PMID- 29444563
TI  - Recent update on coagulation management and hemostatic therapies in liver
      transplantation.
AB  - Liver transplantation is an ever-evolving field and understanding coagulation
      management and hemostatic therapies is essential for good outcomes. In this
      review, we discuss current monitoring tools available in the operating room and
      the hemostatic agents available to control hemostasis. Multifactorial coagulation
      defects are discussed and point-of care monitoring is reviewed to guide selection
      of hemostatic agents when indicated.

PMID- 29444564
TI  - Bio-inspired Edible Superhydrophobic Interface for Reducing Residual Liquid Food.
AB  - Significant wastage of residual liquid food, such as milk, yogurt, and honey, in
      food containers has attracted great attention. In this work, a bio-inspired
      edible superhydrophobic interface was fabricated using U.S. Food and Drug
      Administration-approved and edible honeycomb wax, arabic gum, and gelatin by a
      simple and low-cost method. The bio-inspired edible superhydrophobic interface
      showed multiscale structures, which were similar to that of a lotus leaf surface.
      This bio-inspired edible superhydrophobic interface displayed high contact angles
      for a variety of liquid foods, and the residue of liquid foods could be
      effectively reduced using the bio-inspired interface. To improve the adhesive
      force of the superhydrophobic interface, a flexible edible elastic film was
      fabricated between the interface and substrate material. After repeated folding
      and flushing for a long time, the interface still maintained excellent
      superhydrophobic property. The bio-inspired edible superhydrophobic interface
      showed good biocompatibility, which may have potential applications as a
      functional packaging interface material.

PMID- 29444565
TI  - Elucidating the Solvent Effect on the Switch of the Helicity of Poly(quinoxaline
      2,3-diyl)s: A Conformational Analysis by Small-Angle Neutron Scattering.
AB  - Small-angle neutron scattering (SANS) was used to examine dilute solutions of a
      poly(quinoxaline-2,3-diyl) (PQX) with (R)-2-octyloxymethyl side chains in
      deuterated THF or a mixture of deuterated 1,1,2-TCE and THF (8/2, v/v), in which
      the PQX adopts pure P- and M-helical structures. The structures of the PQX that
      were obtained based on the SANS experiments in combination with theoretical
      calculations suggest that in THF, the chiral side chains of the P-helical PQX are
      extended, whereas in the 1,1,2-TCE/THF mixture, the side chains of the M-helical
      PQX are folded. Consequently, P-helical structures should be preferred in good
      solvents such as THF, which solvate the extended side chains, whereas M-helical
      structures should be preferred in poor solvents such as 1,1,2-TCE, wherein the
      side chains adopt shrunken conformations with maximized van der Waals
      interactions between the side chains. This study thus reveals the first example
      for fully determined nuanced conformations of the side chains of synthetic
      polymers in solution based on SANS experiments and theoretical calculations.

PMID- 29444566
TI  - Chemical Characterization of Novel Natural Products from the Roots of Asian Rice
      ( Oryza sativa) that Control Adipocyte and Osteoblast Differentiation.
AB  - Oryza sativa L. is consumed globally as a staple food, and its roots have been
      used as a Korean and Chinese medical supplement for protection of the stomach and
      lungs and for amelioration of vomiting and fever. In our continuing search for
      biologically effective metabolites from Korean natural materials, we found that
      an EtOH extract of O. sativa root reciprocally regulated adipocyte and osteoblast
      differentiation. Chemical analysis of the EtOH extract using a bioassay-guided
      fractionation protocol led to the isolation and determination of two novel
      lignans, oryzativols A and B, responsible for these regulatory activities. Using
      1D and 2D nuclear magnetic resonance spectroscopic analyses, high-resolution mass
      spectrometry, and circular dichroism analysis, the structures of the novel
      compounds were elucidated. We examined their effects on the regulation of
      mesenchymal stem cell differentiation. Treatment with oryzativol A in the human
      mesenchymal cell line C3H10T1/2 suppressed gene expression of peroxisome
      proliferator activated receptor gamma, which resulted in a reduction in
      adipogenesis. Oryzativol A also enhanced the expression of Runx2 and cellular
      differentiation into osteoblasts in the same mesenchymal stem cell line.

PMID- 29444567
TI  - Formation of Reactive pi-Conjugated Frustrated N/B Pairs by Borane-Induced
      Propargyl Amine Rearrangement.
AB  - N-Propargyltetramethylpiperidine reacts with a series of trans-alkenyl-B(C6F5)2
      compounds to give the substituted alkenyl-bridged frustrated N/B Lewis pairs 5.
      Their structures and spectroscopic features indicate a pronounced participation
      of the mesomeric s-trans-iminium/borata-alkene resonance form. The compounds are
      thought to be formed in a stepwise addition/rearrangement process which is
      initiated by a trans-1,2-amine/borane FLP addition to the carbon-carbon triple
      bond to generate a reactive zwitterionic aziridinium/alkenylborate intermediate.
      Subsequent alkenylborate attack leads to opening of the activated three-membered
      heterocycle with clean formation of the products 5a-c. Treatment of the propargyl
      TMP substrate with B(C6F5)3 gave a stable example of such an aziridinium/borate
      betaine, which was isolated and amply characterized. The products 5a-c are active
      N/B FLPs. They split dihydrogen heterolytically under mild conditions to give the
      respective NH+/BH- products 9a-c. These contain Z-configurated core C?C double
      bonds, which indicates rotational equilibration around the central C-C bond of 5a
      c during this reaction. Structural and chemical features of the 5c system were
      analyzed by DFT calculations.

PMID- 29444568
TI  - Structural Features of Reconstituted Cuticular Wax Films upon Interaction with
      Nonionic Surfactant C12E6.
AB  - The interaction of nonionic surfactant hexaethylene glycol monododecyl ether
      (C12E6) with a reconstituted cuticular wheat wax film has been investigated by
      spectroscopic ellipsometry and neutron reflection (NR) to help understand the
      role of the leaf wax barrier during pesticide uptake, focusing on the mimicry of
      the actions adjuvants impose on the physical integrity and transport of the
      cuticular wax films against surfactant concentration. As the C12E6 concentration
      was increased up to the critical micelle concentration (CMC = 0.067 mM), an
      increasing amount of surfactant mass was deposited onto the wax film. Alongside
      surface adsorption, C12E6 was also observed to penetrate the wax film, which is
      evident from the NR measurements using fully protonated and chain-deuterated
      surfactants. Furthermore, surfactant action upon the model wax film was found to
      be physically reversible below the CMC, as water rinsing could readily remove the
      adsorbed surfactant, leaving the wax film in its original state. Above the CMC,
      the detergency action of the surfactant became dominant, and a significant
      proportion of the wax film was removed, causing structural damage. The results
      thus reveal that both water and C12E6 could easily penetrate the wax film
      throughout the concentration range measured, indicating a clear pathway for the
      transport of active ingredients while the removal of the wax components above the
      CMC must have enhanced the transport process. As the partial removal of the wax
      film could also expose the underlying cutaneous substrate to the environment and
      undermine the plant's health, this study has a broad implication to the roles of
      surfactants in crop care.

PMID- 29444569
TI  - Fe(II)-Catalyzed Isomerization of 5-Chloroisoxazoles to 2 H-Azirine-2-carbonyl
      Chlorides as a Key Stage in the Synthesis of Pyrazole-Nitrogen Heterocycle Dyads.
AB  - 2-(1 H-Pyrazol-1-ylcarbonyl)-2 H-azirines were synthesized by in situ trapping of
      2 H-azirine-2-carbonyl chlorides, generated by Fe(II)-catalyzed isomerization of
      5-chloroisoxazoles, with pyrazoles. According to DFT calculations, the
      selectivity of nucleophilic substitution at the carbonyl group of 2 H-azirine-2
      carbonyl chloride by a pyrazole nucleophile, which is a mixture of two tautomers,
      is controlled by thermodynamic factors. 2-(1 H-Pyrazol-1-ylcarbonyl)-2 H-azirines
      are excellent precursors for the preparation of two other pyrazole-nitrogen
      heterocycle dyads: 5-(1 H-pyrazol-1-yl)oxazoles by photolysis and 1-(1 H-pyrrol-2
      ylcarbonyl)-1 H-pyrazoles by a Ni(II)-catalyzed reaction with 1,3-dicarbonyl
      compounds. 5-(1 H-Pyrazol-1-yl)oxazoles show strong emission in acetonitrile at
      360-410 nm with high quantum yields.

PMID- 29444570
TI  - Pyrethroid Pesticide Exposure and Risk of Primary Ovarian Insufficiency in
      Chinese Women.
AB  - Pyrethroids are a class of widely used insecticides. Female animal studies
      suggested that pyrethroid exposure impaired ovarian function, which resulted in
      similar symptoms of primary ovarian insufficiency (POI). However, it is still
      unknown whether this association applies to women. In this case-control study, a
      total of 172 POI patients and 247 control women were recruited in Zhejiang,
      China. The urinary concentrations of metabolites of pyrethroids, 3-phenoxybenzoic
      acid (3-PBA) and 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), as well as the serum
      concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH)
      and anti-Mullerian hormone (AMH) were determined. The associations of pyrethroid
      metabolites with POI and POI-related hormones were accessed using unconditional
      logistic regression. Higher urinary levels of 3-PBA were significantly associated
      with increased risk of POI [adjusted odds ratio (OR) = 2.344, 95% CI: 1.193-4.607
      for the highest vs lowest quartile of 3-PBA, p = 0.013]. Stratified analyses
      showed that each log increase in urinary 3-PBA concentration was significantly
      associated with an induction in odds of 51.0% being in the highest quartile of
      FSH and 28.6% being in the highest quartile of LH levels, whereas a 25.9%
      reduction in odds of being in the highest quartile of AMH levels (All p for trend
      <0.05). To our knowledge, this is the first case-control study to report an
      association of pyrethroid exposure with increased risk of POI in women.

PMID- 29444571
TI  - Factors Affecting Mercury Stable Isotopic Distribution in Piscivorous Fish of the
      Laurentian Great Lakes.
AB  - Identifying the sources of methylmercury (MeHg) and tracing the transformations
      of mercury (Hg) in the aquatic food web are important components of effective
      strategies for managing current and legacy Hg sources. In our previous work, we
      measured stable isotopes of Hg (delta202Hg, Delta199Hg, and Delta200Hg) in the
      Laurentian Great Lakes and estimated source contributions of Hg to bottom
      sediment. Here, we identify isotopically distinct Hg signatures for Great Lakes
      trout ( Salvelinus namaycush) and walleye ( Sander vitreus), driven by both food
      web and water-quality characteristics. Fish contain high values for odd-isotope
      mass independent fractionation (MIF) with averages ranging from 2.50 (western
      Lake Erie) to 6.180/00 (Lake Superior) in Delta199Hg. The large range in odd-MIF
      reflects variability in the depth of the euphotic zone, where Hg is most likely
      incorporated into the food web. Even-isotope MIF (Delta200Hg), a potential tracer
      for Hg from precipitation, appears both disconnected from lake sedimentary
      sources and comparable in fish among the five lakes. We suggest that similar to
      the open ocean, water-column methylation also occurs in the Great Lakes, possibly
      transforming recently deposited atmospheric Hg deposition. We conclude that the
      degree of photochemical processing of Hg is controlled by phytoplankton uptake
      rather than by dissolved organic carbon quantity among lakes.

PMID- 29444572
TI  - Unraveling the Role of a Flexible Tetradentate Ligand in the Aerobic Oxidative
      Carbon-Carbon Bond Formation with Palladium Complexes: A Computational
      Mechanistic Study.
AB  - Mechanistic details of the aerobic oxidative coupling of methyl groups by a novel
      (MeL)PdII(Me)2 complex with the tetradentate ligand, MeL = N, N-dimethyl-2,11
      diaza[3.3](2,6)pyridinophane, has been explored by density functional theory
      calculations. The calculated mechanism sheds light on the role of this ligand's
      flexibility in several stages of the reaction, especially as the oxidation state
      of the Pd changes. Ligand flexibility leads to diverse axial coordination modes,
      and it controls the availability of electrons by modulating the energies of high
      lying molecular orbitals, particularly those with major d z2 character. Solvent
      molecules, particularly water, appear essential in the aerobic oxidation of PdII
      by lowering the energy of the oxygen molecule's unoccupied molecular orbital and
      stabilizing the PdX-O2 complex. Ligand flexibility and solvent coordination to
      oxygen are essential to the required spin-crossover for the transformation of
      high-valent PdX-O2 complexes. A methyl cation pathway has been predicted by our
      calculations in transmetalation between PdII and PdIV intermediates to be
      preferred over methyl radical or methyl anion pathways. Combining an axial and
      equatorial methyl group is preferred in the reductive elimination pathway where
      roles are played by the ligand's flexibility and the fluxionality of trimethyl
      groups.

PMID- 29444574
TI  - Spotlights: Volume 9, Issue 4.

PMID- 29444573
TI  - Optical Properties of Dissolved Organic Matter and Their Relation to Mercury
      Concentrations in Water and Biota Across a Remote Freshwater Drainage Basin.
AB  - Dissolved organic matter (DOM) includes an array of carbon-based compounds that
      vary in size and structure and have complex interactions with mercury (Hg)
      cycling in aquatic systems. While many studies have examined the relationship
      between dissolved organic carbon concentrations ([DOC]) and methyl Hg
      bioaccumulation, few studies have considered the effects of DOM composition
      (e.g., protein-content, aromaticity). The goal of this study was to explore the
      relationships between total and methyl [Hg] in water, invertebrates, and fish and
      optically derived measures of DOM composition from 47 lake and river sites across
      a boreal watershed. Results showed higher aqueous total [Hg] in systems with more
      aromatic DOM and higher [DOC], potentially due to enhanced transport from
      upstream or riparian areas. Methyl [Hg] in biota were all positively related to
      the amount of microbial-based DOM and, in some cases, to the proportions of
      labile and protein-like DOM. These results suggest that increased Hg
      bioaccumulation is related to the availability of labile DOM, potentially due to
      enhanced Hg methylation. DOM composition explained 68% and 54% more variability
      in [Hg] in surface waters and large-bodied fish, respectively, than [DOC] alone.
      These results show that optical measures of DOM characteristics are a valuable
      tool for understanding DOM-Hg biogeochemistry.

PMID- 29444575
TI  - [Classification of posterior malleolar fractures in ankle fractures].
AB  - The study presents an overview of the most common radiography and CT-based
      classifications of posterior malleolar fractures in ankle fracture-dislocations.
      Their analysis has shown that posterior malleolar fractures largely vary in size
      and shape. Evaluation of fractures by plain radiographs is inadequate. A detailed
      assessment of the fragment shape and course of fracture lines requires CT
      examination in all three projections, followed by 3D CT reconstructions.Key
      words: ankle fracture - dislocations trimalleolar fractures posterior malleolar
      fractures classification.

PMID- 29444576
TI  - [Fractures of the fifth metatarsal base].
AB  - Fractures of the fifth metatarsal base are among the most common fractures of the
      foot. They are typically caused by indirect violence during sports activities.
      This region is also a site where stress fractures occur frequently. Diagnosis is
      based on the patients medical history, clinical examination and imaging methods.
      The fundamental imaging method is radiography of the foot in three views. MRI is
      used primarily for early diagnosis of stress fractures. CT examination is
      beneficial mainly in complex foot injuries, in order to rule out associated
      fractures. Several classifications of fractures of the fifth metatarsal base have
      been published in the last 50 years, categorizing these fractures in terms of
      their location, appearance of the fracture line, type of treatment, healing and
      complications. Currently, the most frequently used one is the classification
      developed by Lawrence and Botte. Non-operative treatment is indicated in
      undisplaced or minimally displaced fractures, fractures in elderly patients and
      in patients contraindicated for surgery. The method of choice in undisplaced
      fractures is the Barouk boot with partial weight-bearing as tolerated by the
      patient, while displaced fractures up to 2 mm are fixed in a low plaster cast
      (Essex-Lopresti shoe). Operative treatment is indicated in fractures displaced by
      more than 2 mm or involving more than 30% of the articular surface of the cuboid
      metatarsal joint. Internal fixation is most commonly performed with the use of
      intramedullary screw, tension wire band, K-wires or plates. Stress fractures are
      preferably treated by surgery to reduce the risk of non-union, delayed healing
      and the risk of refractures. The most common complications associated with
      treatment of fractures of the fifth metatarsal base include delayed healing, non
      union development, refractures and patient discomfort.Key words: fractures of the
      fifth metatarsal base - diagnosis - treatment - complications.

PMID- 29444577
TI  - Classification of scapular body fractures.
AB  - INTRODUCTION: The aim of this study is to present, on the basis of 3D CT
      reconstructions of 187 of scapular body fractures, a clinically oriented
      classification respecting the biomechanical architecture of the scapula. METHODS:
      In a series of 375 scapula fractures we identified 187 body fractures in187
      patients (157 men, 30 women) with the mean age of 48 years (range; 16100 years).
      3D CT reconstructions were obtainedof all fractures, to allow an objective
      evaluation of the fracture pattern. A total of 46 patients were operated on and
      their intraoperative findings were correlated with 3D CT reconstructions.
      Scapular body fractures were deemed to be only those fractures that passed
      through the biomechanical body of the scapula, i.e. involved at least one of the
      pillars. Excluded from the study were fractures of the superior angle and of the
      superior border of the scapula as they were only marginal fractures leaving both
      pillars intact; scapular neck fractures defined as extra-articular two-part
      fractures of the lateral angle separating the glenoid from the scapular body; and
      fractures of the inferior angle of the scapula. Evaluation focused on the course
      of fracture lines, their relationship to the two pillars, and the number of
      fragments. A separate fragment was considered to be only such a fragment that
      carried part of the circumference of the biomechanical body. The intercalary
      fragmentsbroken off the central part of the infraspinous fossa were not included.
      RESULTS: We identified three basic groups of scapular body fractures, i.e. those
      involving only the spinal pillar, those involving only the lateral pillar and
      fractures affecting both pillars. Our series included 12 fractures of the spinal
      pillar, of these in 8 cases the main fracture line passed vertically from the
      supraspinous fossa of the central part of the pillar toward the medial border of
      the infraspinous fossa; in 4 cases the scapular spine base was broken off the
      scapular body. In all the cases, the lateral pillar was left intact and fragments
      were displaced only insignificantly. Therefore all these fractures were treated
      non-operatively. A total of 143 fractures involved the lateral pillar. All of
      them were fractures of the infraspinous portion of the scapular body, i.e. the
      infraspinous fossa, with the main fracture line propagating from the lateral
      pillar. This fracture pattern was divided on the basis of the number of
      circumference fragments into three subtypes, namely two-part (88), three-part
      (31) and comminuted (24) fractures. Fractures of both pillars were recorded in 32
      cases. This fracture had two patterns, one (11 fractures) with a fracture line
      running through the spinal pillar close to the spinomedial angle to the superior
      angle of the scapula, and the other (21 fractures) with the main fracture line
      passing through the weakened central part of the scapular spine. This comminuted
      type was the most severe injury to the scapular body. The fracture line always
      propagated through the weakened central part of the spinal pillar. The fracture
      of the lateral pillar was displaced in all cases more than that of the spinal
      pillar. CONCLUSION: Classification of scapular body fractures based on
      involvement of the pillars of the scapular body is logical and simple. It always
      requires a 3D CT reconstruction, including subtraction of the surrounding bones.
      It respects the anatomical structure of the scapula and may serve also as a
      therapeutic guidance in preoperative planning.Key words: scapula scapula
      fractures scapular body fractures - classification classification of scapular
      body fractures.

PMID- 29444578
TI  - [Anatomy of fractures of the inferior scapular angle].
AB  - INTRODUCTION: The aim of this study is to describe the anatomy of fractures of
      the inferior angle and the adjacent part of the scapular body, based on 3D CT
      reconstructions. METHOD: In a series of 375 scapular fractures, we identified a
      total of 20 fractures of the inferior angle of the scapular body (13 men, 7
      women), with a mean patient age of 50 years (range 3373). In all fractures, 3D CT
      reconstructions were obtained, allowing an objective evaluation of the fracture
      pattern with a focus on the size and shape of the inferior angle fragment,
      propagation of the fracture line to the lateral and medial borders of the
      infraspinous part of the scapular body, fragment displacement and any additional
      fracture of the ipsilateral scapula and the shoulder girdle. RESULTS: We
      identified a total of 5 types of fracture involving the distal half of the
      infraspinous part of the scapular body. The first type, recorded in 5 cases,
      affected only the apex of the inferior angle, with a small part of the adjacent
      medial border. The second type, occurring in 4 cases, involved fractures
      separating the entire inferior angle. The third type, represented by 4 cases, was
      characterized by a fracture line starting medially close above the inferior angle
      and passing proximolaterally. The separated fragment had a shape of a big drop,
      carrying also the distal half of the lateral pillar in addition to the inferior
      angle. In the fourth type identified in 5 fractures, the separated fragment was
      formed both by the inferior angle and a variable part of the medial border. The
      fifth type, being by its nature a transition to the fracture of the infraspinous
      part of the body, was recorded in 2 cases, with the same V-shaped fragment.
      CONCLUSION: Fractures of the inferior angle and the adjacent part of the scapular
      body are groups of fractures differing from other infraspinous fractures of the
      scapular body. Although these fractures are highly variable in terms of shape,
      they have the same course of fracture line and the manner of displacement.Key
      words: scapula scapula fractures scapular body fractures inferior angle
      classification of scapular body fractures.

PMID- 29444579
TI  - [Quality of nephrolithiasis surgical treatment - what is it influenced by?]
AB  - INTRODUCTION: Identifying factors effecting the quality of nephrolithiasis
      surgical treatment could improve medical care for patients suffering from kidney
      stone disease. The objective of the article is to identify factors influencing
      reintervention rate after surgical treatment of kidney stone disease either by
      percutaneous nephrolitholapaxy or flexible ureterorenoscopy. METHOD: A
      retrospective study was conducted on 149 patients who underwent a surgery for a
      kidney stone disease at the Urological department of F.D. Roosevelt hospital
      Banska Bystrica from January 2015 till June 2015. The cohort included 60 women at
      average age of 57 (range 28-91) and 89 men at average age of 58 (range 30-92).
      Patients were treated by percutaneous litholapaxy (67 cases) and flexible
      ureterorenoscopy (82 cases, including 72 using dusting technique). Factors with
      potential influence on probability of repeated intervention during following 12
      months have been studied and statistically analyzed. For the statistical analysis
      we used the generalized linear regression framework (GLM Generalized Linear
      Model) with the stepwise forward modeling approach. RESULTS: Using the
      significance level of 5% the statistically significant factors affecting the
      probability of the re-intervention for ipsilateral kidney stone disease are the
      stone size (p-value 0.0035) and the postoperative stone free status (p-value
      0.0418). Other studied factors as demographical data (age, gender), surgical
      method (percutaneous nephrolitolapaxy or flexible ureterorenoscopy), stone count,
      postoperative draining system (nefrostomy or JJ stent) did not have any
      statistically significant impact. CONCLUSION: Patients could benefit from early
      diagnosis which could lead to earlier identification of smaller stones. Perfect
      operative technique with intraoperative achievement of stone free status is
      important to lower the need of repeated intervention.Key words: kidney stone
      disease - reintervention residual fragments.

PMID- 29444580
TI  - [Our experience with left-sided retroperitoneal approach to resection of
      abdominal aortic aneurysm].
AB  - INTRODUCTION: At most vascular surgery departments, transperitoneal approach
      predominates in resections of the aortic aneurysms. For difficult reconstructions
      of the aorta in the visceral segment, a left flank retroperitoneal approach is
      used most frequently. METHOD: The authors retrospectively evaluate the left
      retroperitoneal approach in the management of abdominal aortic aneurysms during a
      10-year period. From the total number of 445 operated patients, the left-sided
      retroperitoneal approach was used in 23 cases. RESULT: All operated patients
      survived. Average hospital stay was 10 days in the case of elective operations.
      CONCLUSION: Based on favorable results, the authors confirm that left-sided
      retroperitoneal approach is rightly considered as a choice in the technically
      demanding reconstruction of the aorta in the visceral segment.Key words: aortic
      aneurysm visceral segment of the aorta retroperitoneal approach.

PMID- 29444581
TI  - [The effect of circulating tumor cells on the survival of patients with
      pancreatic cancer 5-year results].
AB  - INTRODUCTION: Pancreatic cancer (PDAC) is one of the most aggressive
      malignancies. Its incidence increases worldwide and, despite the developments in
      cancer research, mortality rates have not decreased. Poor prognosis of the
      disease is due to many factors, mainly late diagnosis. Distant metastases and
      peritoneal carcinomatosis are caused by hematogenous and lymphogenous spreading
      of the tumorous cells. One of the factors that may influence patient survival are
      so-called circulating tumor cells (CTCs). The aim of our work was to evaluate the
      possible influence of CTCs on the survival of patients with PDAC. METHOD: We
      included patients who underwent a radical or palliative surgical intervention at
      the First Department of Surgery of Medical Faculty and University Hospital in
      Olomouc between 1 January 2008 and 31 December 2012. The required samples for
      CTCs detection were taken from each patient. The detection of the CTCs was
      performed using real-time RT-PCR. The results were statistically processed and
      evaluated. RESULTS: We included 126 patients in total, of which 88 were treated
      radically and 38 received palliative treatment. Mean age was 63 years in patients
      with radical and 64 years in patients with palliative surgery. Mean survival time
      in radically treated patients was 29.6 months, in patients with palliative
      treatment the mean survival time was 8.5 months. The survival time of radically
      treated patients with CTCs was 27.2 months, without CTCs it was 33.8 months.
      CONCLUSION: We did not prove a statistically significant difference in survival
      between radically treated PDAC patients with and without detected CTCs in our
      work.Key words: pancreatic cancer - circulating tumor cells survival.

PMID- 29444582
TI  - Short Communication: Dolutegravir-Based Regimens Are Active in Integrase Strand
      Transfer Inhibitor-Naive Patients with Nucleoside Reverse Transcriptase Inhibitor
      Resistance.
AB  - In the SAILING study, dolutegravir demonstrated superior virologic efficacy
      compared with raltegravir in treatment-experienced, integrase strand transfer
      inhibitor (INSTI)-naive patients with HIV-1 who harbored resistance to >=2
      antiretroviral drug classes. Significantly fewer dolutegravir-treated patients
      demonstrated virologic failure with treatment-emergent resistance than
      raltegravir-treated patients through 48 weeks. Investigator-selected background
      therapy (ISBT) included at least one fully active agent, selected on the basis of
      resistance analysis. Genotypic and phenotypic resistance testing were performed
      on baseline and time-of-failure samples from patients with protocol-defined
      virologic failure (PDVF). A post hoc analysis of SAILING (N = 715; 354
      dolutegravir, 361 raltegravir) assessed efficacy in subpopulations defined by
      ISBT activity, resistance profiles, and treatment history. When ISBT contained
      only nucleoside reverse transcriptase inhibitors (NRTIs), PDVF occurred in 0%
      (0/32) of dolutegravir-treated patients and 21.9% (7/32) of raltegravir-treated
      patients (p = .005). In patients harboring M184 V whose ISBT contained lamivudine
      or emtricitabine plus a second NRTI, 0% (0/13) of dolutegravir- and 33.3% (4/12)
      of raltegravir-treated patients (p = .026) experienced PDVF. Among patients
      receiving protease inhibitor (PI)-containing ISBT, 6.0% (18/300) of dolutegravir
      treated patients versus 11.8% (36/305) of raltegravir-treated patients (p = .012)
      experienced PDVF. Darunavir/ritonavir was part of ISBT in 130 dolutegravir
      treated patients and 145 raltegravir-treated patients; 6 (4.6%) and 12 (8.3%),
      respectively, experienced PDVF (difference -3.7%; 95% confidence interval: -10.1%
      to 2.5%; p = .256). There was no or less virologic failure in treatment
      experienced, INSTI-naive subjects receiving dolutegravir versus raltegravir, even
      when the ISBT was suboptimal or NRTI resistance was present at baseline. These
      findings are not explained by the use of PI/ritonavir-containing ISBT.

PMID- 29444583
TI  - Barriers to a healthy lifestyle for three- to four-year-old children of
      Australian-born and overseas-born mothers with post-gestational diabetes: An
      Australian qualitative study.
AB  - Children of mothers affected by gestational diabetes mellitus (GDM) are at higher
      risk of long-term cardio-metabolic diseases. We explore the diet and physical
      activity knowledge and practices of Australian-born and overseas-born mothers
      with GDM history, for their three- to four-year-old children following antenatal
      health promotion education at a tertiary hospital. We conducted face-to-face,
      semi-structured interviews with 8 Australian-born and 15 overseas-born mothers
      with a history of GDM. Findings indicated that mothers of both groups were
      unaware of the increased health risks of their GDM for their children and could
      not recall receiving specific dietary or physical activity advice aimed at future
      child health. Their understanding of the diet and physical activity
      recommendations was inconsistent. Mothers of both groups expressed concern about
      the lack of reiteration of child health promotion messages following childbirth,
      particularly at postnatal follow-up visits. Diet and physical activity of the
      children of overseas-born mothers were adversely affected by inadequate maternal
      understanding of the recommendations due to language barriers, and child weight,
      healthy eating, and physical activity patterns derived from their home countries.
      We recommend enhanced health education for women with GDM on the future child
      health risks and their reduction by healthy lifestyle choices. This needs to be
      culturally relevant and reiterated after pregnancy.

PMID- 29444584
TI  - Complication Rates and Short-Term Outcomes After Operative Hammertoe Correction
      in Older Patients.
AB  - BACKGROUND: Hammertoe deformities are the most common lesser toe deformity. To
      date, no studies have looked at outcomes of operative management in the geriatric
      population, which may be at greater risk for complications or functional
      compromise because of comorbidities. METHODS: Data on 58 patients undergoing
      operative correction of hammertoe deformities were prospectively collected.
      Clinical outcomes were assessed using preoperative and postoperative visual
      analogue scale (VAS) and Short Form Health Survey (SF-36) scores with a minimum
      of 6-month follow-up. Patients were divided into 2 groups on the basis of age at
      the time of surgery: younger than 65 and 65 and older. Complication rates and
      mean VAS and SF-36 improvement were compared. Forty-seven patients met inclusion
      criteria (7 men, 40 women), with 26 patients (37 toes) in the younger cohort and
      21 patients (39 toes) in the older cohort. RESULTS: Overall, patients
      demonstrated significant improvement from baseline to 6 and 12 months
      postoperatively in VAS ( P < .001 and P < .001) and SF-36 ( P < .001 and P <
      .001) scores. Mean improvement in VAS and SF-36 scores was not significantly
      different between the groups at 6 and 12 months postoperatively. Complications
      occurred in 13.5% and 10.3% of patients in the younger and older cohorts,
      respectively. CONCLUSIONS: Outcomes of operative correction of hammertoe
      deformities in older patients were similar to outcomes in younger patients after
      greater than 6 months of follow-up. Overall improvement in VAS and SF-36 was
      statistically significant for both cohorts. There was no associated increase in
      complications for older patients. LEVEL OF EVIDENCE: Level, III comparative
      series.

PMID- 29444585
TI  - Editorial Comment on: Fluid Dynamic Analysis of Hand-Pump Infuser and UROMAT
      Endoscopic Automatic System for Irrigation Through a Flexible Ureteroscope by
      Lama et al.

PMID- 29444587
TI  - Uterine artery embolization in a sheep model: biodegradable versus non-degradable
      microspheres.
AB  - Background Transarterial embolization with particles is a relatively common
      treatment method in both malignant and benign disorders. Permanent occlusion of
      the uterine arteries may sometimes be disadvantageous. Purpose To compare the
      local tissue effects, possible side effects, and extent of recanalization
      following uterine artery embolization, using either degradable or non-degradable
      microspheres in a sheep model. Material and Methods In 22 female sheep, the
      uterine artery (UA) was unilaterally, superselectively embolized, with either
      degradable starch microspheres-DSM (group A) or calibrated gelatin coated
      spherical shape tris-acryl microspheres-TGMS (group B). The completion of
      embolization was confirmed by angiography. The animals were kept in the animal
      research facilities for 14 days and sacrificed following new angiographic
      evaluation. Gross and histological examination of the uterus and other organs was
      performed. Results The procedure was successful in all animals. At final
      angiographic evaluation recanalization was found in 82% of the ewes in group A
      and in 18% in group B. At histopathological examination, tissue impairment was
      similar in both groups, whereas vascular changes were more pronounced in the TGMS
      group. Conclusion Embolization with DSM was associated with significantly higher
      degree of recanalization, than after embolization with TGMS.

PMID- 29444586
TI  - Sex differences in pericardial adipose tissue assessed by PET/CT and association
      with cardiometabolic risk.
AB  - Background Recent studies suggest that pericardial adipose tissue (PAT) is
      associated with whole body adiposity and insulin resistance. Moreover, the
      incidence of cardiovascular disease (CVD) differs between men and women. Although
      CVD is more prevalent in men, women suffering from CVD have a higher mortality
      compared to men. Differences in PAT may account for some of the observed sex
      differences in manifestations of CVD. Purpose To assess pericardial adipose
      tissue (PAT) as a biomarker for cardiometabolic risk and to assess potential sex
      differences. Material and Methods We studied 303 individuals (151 women, 152 men;
      mean age = 57 +/- 17 years) across the weight spectrum. PAT and abdominal adipose
      tissue were quantified using clinical computed tomography (CT) scans obtained as
      part of a positron emission tomography (PET)/CT. Cardiometabolic risk factors
      were assessed from medical records. Linear regression and receiver operating
      characteristic (ROC) curve analyses were performed to evaluate associations
      between PAT and cardiometabolic risk. Results PAT was higher in overweight and
      obese individuals compared to lean individuals and higher in men compared to
      women. PAT was positively associated with body mass index, abdominal fat ( P <
      0.0001), fasting glucose, and serum lipids ( P < 0.05) with stronger associations
      in women than in men. PAT was accurate in detecting the prevalence of the
      metabolic syndrome with 74% sensitivity and 76% specificity (AUC = 0.80).
      Conclusion PAT is associated with measures of cardiometabolic risk and these
      associations are stronger in women compared to men. PAT could serve as a
      biomarker for opportunistic screening for cardiometabolic risk in patients
      undergoing chest CT.

PMID- 29444588
TI  - Periaortic Adipose Tissue Compared With Peribrachial Adipose Tissue Mass as
      Markers and Possible Modulators of Cardiometabolic Risk.
AB  - Increased perivascular fat mass contributes to cardiometabolic risk (CMR). High
      peribrachial adipose tissue (PBAT) associates with insulin resistance
      independently of established CMR parameters. It is unknown to what extent
      periaortic adipose tissue (PAAT) may have a similar impact. In 95 participants,
      precise quantification of total adipose tissue, PBAT, PAAT, visceral adipose
      tissue (VAT), and liver fat (LF) content was performed by whole-body magnetic
      resonance imaging. Insulin sensitivity was determined by oral glucose tolerance
      test and carotid intima-media thickness (cIMT) by high-resolution ultrasound. In
      univariate analyses, PAAT correlated with PBAT (beta = .65, P < .0001). A
      negative correlation of PAAT (beta = -.35, P = .0002) and PBAT (beta = -.43, P <
      .0001) with insulin sensitivity was observed. While in a stepwise forward
      regression analysis the relationship of PAAT with insulin sensitivity was no
      longer significant after adjustment for VAT, LF content, and other CMR factors (
      P = 0.42), PBAT still correlated with insulin sensitivity ( r2 = .35, P = .01).
      The association between PAAT and cIMT (beta = .49, P < .0001) remained
      significant after adjustment for these variables ( r2 = .42, P = .0001). Although
      PAAT and PBAT strongly correlate, PAAT is not associated with insulin resistance,
      but with cIMT. Therefore, PAAT and PBAT may act differently as possible
      modulators of insulin resistance and subclinical atherosclerosis.

PMID- 29444589
TI  - Increased Risk of Peripheral Arterial Disease in Patients With Abdominal Aortic
      Aneurysm: A Retrospective Cohort Study (Version 5).
AB  - Studies evaluating the risk of peripheral arterial disease (PAD) in patients with
      abdominal aortic aneurysm (AAA) are limited. We used insurance claims data of
      Taiwan to establish a cohort of 6590 patients with AAA newly diagnosed from 2000
      to 2008 and 6590 controls without AAA matched by propensity score. The subsequent
      incidence density rates of PAD were estimated in both cohorts by the end of 2011,
      and the AAA cohort to the non-AAA cohort hazard ratios (HRs) of PAD were
      calculated using Cox proportional hazards models. The incidence density of PAD in
      the AAA cohort was 3.7-fold greater than that in the non-AAA cohort (14.1 vs 3.66
      per 1000 person-years) with an adjusted HR of 3.56 (95% confidence interval [CI]
      = 2.89-4.39). For those without comorbidities, PAD in the AAA cohort was 7.4-fold
      greater than that in the non-AAA cohort (12.0 vs 1.61 per 1000 person-years) with
      an adjusted HR of 6.70 (95% CI = 4.43-10.1). The incidence of PAD in patients
      with ruptured AAA was lower than that in patients without rupture (6.95 vs 15.0
      per 1000 person-years). This study demonstrates that patients with AAA are at
      increased risk of developing PAD.

PMID- 29444590
TI  - "STONE TREES": Metabolic Evaluation and Medical Treatment of the Urolithiasis
      Patient Made Easy.
AB  - In this review, a simplified straightforward algorithmic approach to the
      metabolic evaluation and treatment of the at-risk or recurrent urolithiasis
      patient is provided. Eight diagnoses and eight therapies are provided, which
      cover over 95% of renal stone disease.

PMID- 29444591
TI  - Reflections on a Collaborative, Cross-Discipline Experience.

PMID- 29444592
TI  - Antidepressant-Like Effects of Vaccinium bracteatum in Chronic Restraint Stress
      Mice: Functional Actions and Mechanism Explorations.
AB  - The fruit of Vaccinium bracteatum Thunb. (VBF) is commonly known as the oriental
      blueberry in Korea. The aim of this study was to evaluate the antidepressant-like
      effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress
      (CRS) and to identify the underlying mechanisms of its action. The behavioral
      effects of VBFW were assessed in the forced swim test (FST) and open field test
      (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition
      to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt)
      signaling pathway were evaluated. VBFW treatment significantly reduced the
      immobility time and increased swimming time in FST without altering the locomotor
      activity in unstressed mice. Furthermore, CRS mice treated with VBFW exhibited a
      significantly decreased immobility time in FST and serum CORT, increased
      locomotor activity in OFT, and enhanced brain monoamine neurotransmitters.
      Similarly, VBFW significantly upregulated the ERKs/Akt signaling pathway in the
      hippocampus and PFC. In addition, VBFW may reverse CORT-induced cell death by
      enhancing cyclic AMP-responsive element-binding protein expression through the up
      regulation of ERKs/Akt signaling pathways. In addition, VBFW showed the strong
      antagonistic effect of the 5-HT[Formula: see text] receptor by inhibiting 5-HT
      induced intracellular Ca[Formula: see text] and ERK1/2 phosphorylation. Our study
      provides evidence that antidepressant-like effects of VBFW might be mediated by
      the regulation of monoaminergic systems and glucocorticoids, which is possibly
      associated with neuroprotective effects and antagonism of 5-HT[Formula: see text]
      receptor.

PMID- 29444593
TI  - Validation of an automated ultraperformance liquid chromatography IgG N-glycan
      analytical method applicable to classical galactosaemia.
AB  - Background Classical galactosaemia (OMIM #230400) is a rare disorder of
      carbohydrate metabolism caused by deficiency of the galactose-1-phosphate
      uridyltransferase enzyme. The pathophysiology of the long-term complications,
      mainly cognitive, neurological and female fertility problems, remains poorly
      understood. Current clinical methods of biochemical monitoring lack precision and
      individualization with an identified need for improved biomarkers for this
      condition. Methods We report the development and detailed validation of an
      automated ultraperformance liquid chromatography N-glycan analytical method of
      high peak resolution applied to galactose incorporation into human serum IgG.
      Samples are prepared on 96-well plates and the workflow features rapid
      glycoprotein denaturation, enzymatic glycan release, glycan purification on solid
      supported hydrazide, fluorescent labelling and post-labelling clean-up with solid
      phase extraction. Results This method is shown to be accurate and precise with
      repeatability (cumulative coefficients of variation) of 2.0 and 8.5%,
      respectively, for G0/G1 and G0/G2 ratios. Both serum and processed N-glycan
      samples were found to be stable at room temperature and in freeze-thaw
      experiments. Conclusions This high-throughput method of IgG galactose
      incorporation is robust, affordable and simple. This method is validated with the
      potential to apply as a biomarker for treatment outcomes for galactosaemia.

PMID- 29444594
TI  - Placental Tissue in Colon and Liver.

PMID- 29444595
TI  - Dietary Supplements and the High-Performance Athlete.

PMID- 29444596
TI  - Activation of the cannabinoid receptor 1 by ACEA suppresses senescence in human
      primary chondrocytes through sirt1 activation.
AB  - Senescence of chondrocytes and cartilage degeneration induced by the
      proinflammatory cytokine interleukin-1beta is associated with the pathogenesis of
      osteoarthritis. The cannabinoid receptor 1 has been involved in the pathological
      development of various diseases. Here, we evaluated whether activation of
      cannabinoid receptor 1 using its selective agonist arachidonyl-2-chloroethylamide
      had an influence on cellular senescence induced by interleukin-1betain human
      chondrocytes. Our findings demonstrate that agonist arachidonyl-2
      chloroethylamidedecreased senescence-associated beta-galactosidase activity and
      cell cycle arrest in the G0/G1 phase induced by interleukin-1beta. Importantly,
      our results display interleukin-1betatreatment significantly increased the
      expressions of senescence genes (caveolin-1, PAI-1 and p21), which were prevented
      by agonist arachidonyl-2-chloroethylamide treatment. However, it was noticed that
      these functions of agonist arachidonyl-2-chloroethylamide were abolished by the
      cannabinoid receptor 1 selective antagonist AM251, suggesting the involvement of
      cannabinoid receptor 1. Also, our results indicate that agonist arachidonyl-2
      chloroethylamide enhanced the expression of sirt1. These findings suggest that
      activation of cannabinoid receptor 1 by agonist arachidonyl-2-chloroethylamide
      might have a protective effect against pro-inflammatory cytokines such as
      interleukin-1beta-induced chondrocytes senescence in osteoarthritis patients.
      Impact statement Senescence of chondrocytes and cartilage degeneration induced by
      the proinflammatory cytokine interleukin-1beta (IL-1beta) are associated with the
      pathogenesis of osteoarthritis (OA). Here we found that: (a) the CB1 agonist ACEA
      abolished IL-1beta-induced senescence and cell arrest in chondrocytes; (b) the
      CB1 agonist ACEA also abolished IL-1beta-induced expression of caveolin-1, PAI-1,
      and p21;

PMID- 29444598
TI  - Venous outlet syndrome caused by capillary hemangioma of the subclavian vein.
AB  - We report a case of intravenous lobular capillary hemangioma in the subclavian
      vein, causing venous thoracic outlet syndrome. A 32-year-old woman was referred
      to our unit with facial and left arm oedema. Ultrasound evaluation, computed
      tomography and magnetic resonance imaging showed a hypervascular mass in the
      middle portion of the subclavian vein, with arrest of venous flow. Through an
      infraclavicular approach, we excised the venous axis with the endovascular
      palpable tumour that extended from the axillary-subclavian junction to the
      jugular-subclavian junction, without reconstruction. The postoperative period was
      uneventful. The patient recovered well without recurrence at one year from
      surgery.

PMID- 29444597
TI  - An experimental model for hypertensive crises emergencies: Long-term high-fat
      diet followed by acute vasoconstriction stress on spontaneously hypertensive
      rats.
AB  - Currently, the prevention and treatment of hypertensive crises especially when it
      occurs with serious adverse outcomes have led to worldwide controversy. Despite
      of clinical possibilities of multiple agents, clinical failures still occur
      frequently. Therefore, early evaluations and observations of different therapies
      on appropriate animals should be emphasized. In the present study, an animal
      model for hypertensive crises emergencies was firstly established and
      experimentally testified. Five-month-male spontaneously hypertensive rat was
      consecutively fed with 60%-Kcal fat diet for four, six, and eight weeks with body
      weight and blood pressure monitored every two weeks, and then followed by an
      acute vasoconstriction stress of 5-min ice-bath treatment in the 4-h time
      interval of two adrenaline injections (0.8 mg/kg). Forty-four biochemical
      parameters were detected, covering hepatic and renal function, blood glucose and
      lipid levels, myocardial enzymes and energy metabolisms, blood coagulative and
      anti-coagulative system, oxidative stress and anti-inflammatory cytokine, blood
      viscosity, and RAAS system. Six tissues including heart, brain, liver, kidney,
      coronary arteries, and mesenteries were removed for pathological observations
      with hematoxylin-eosin staining. As a result, multi-organ dysfunctions in the
      heart, brain, liver, kidney, vascular endothelium, and blood system were
      testified in the modeling rats at weeks 6 and 8. In conclusion, severe
      consequences of this animal model were highly similar to those in hypertensive
      crises emergencies, which could be further utilized in the early intervention of
      hypertensive crises emergencies including the possible risk factors control and
      efficient therapies assessment. Impact statement In the late 90s, numerous
      reports predicted that 1-2% of hypertensive individuals would undergo
      hypertensive crises (HPC) and figures reached as high as 7% when no
      antihypertensive therapies were administrated. Currently, clinical failures
      appear frequently due to the improper or excessive medication regimen instead of
      the illness itself. Therefore, early evaluations and observations of HPC on
      appropriate animal models ahead of patients should be discussed and emphasized
      more widely. In the present study, an appropriate animal model for HPC
      emergencies was firstly established, in which the consequences of long-term high
      fat diet feeding followed by an acute vasoconstriction stress on the
      spontaneously hypertensive rats were experimentally testified. The proposed model
      would have a wide application prospects in early intervention of HPC emergencies
      including the controls of possible risk factors and assessments of efficient
      therapies.

PMID- 29444599
TI  - Correlation between epicardial fat thickness and aortic valve sclerosis.
AB  - Background Epicardial fat is a true visceral fat deposit with adverse effects
      through the secretion of numerous proinflammatory and proatherogenic cytokines.
      Previous studies showed an association between aortic valve sclerosis and
      coronary artery disease. The aim of this study was to determine the correlation
      between epicardial fat thickness and aortic valve sclerosis. Method The study
      involved 225 patients who were admitted for coronary angiography due to new-onset
      angina. They underwent transthoracic echocardiography and epicardial fat
      thickness was determined. The sclerosis scoring of each aortic cusp, average
      aortic valve sclerosis score index, and left ventricular ejection fraction were
      determined. The variables of left ventricular diastolic function obtained
      included the early diastolic velocity determined by transmitral pulsed Doppler,
      and early mitral annular velocity measured by tissue Doppler. Results Patients
      with an epicardial fat thickness >=7 mm were older ( p = 0.006), with more
      hypertension ( p = 0.045) and hyperlipidemia ( p < 0.001). Their average aortic
      valve sclerosis score index was higher (1.4 +/- 1.02 vs. 0.86 +/- 0.85, p =
      0.001), and left ventricular ejection fraction and early mitral annular velocity
      were lower ( p < 0.001 and 0.03, respectively). They also exhibited more left
      ventricular hypertrophy ( p = 0.026) and a trend towards more significant
      coronary artery disease and 3-vessel disease ( p = 0.086 and 0.073,
      respectively). Conclusion Our findings confirm that epicardial fat as a marker of
      visceral adipose tissue may have an important role in promoting inflammatory and
      atherosclerotic changes in the aortic valve.

PMID- 29444600
TI  - Extracorporeal membrane oxygenation as a rescue measure after thoracic surgery.
AB  - Background Extracorporeal membrane oxygenation is used for many different
      conditions including respiratory distress, cardiogenic shock, and trauma. In
      these patient groups, extracorporeal membrane oxygenation has been extensively
      studied. Recently, it has been used as a rescue measure in patients experiencing
      acute respiratory distress after thoracic surgery. The goal of our study was to
      examine the efficacy and cost-effectiveness of extracorporeal membrane
      oxygenation as a rescue measure after thoracic surgery at a single center.
      Methods We conducted a retrospective review of all patients who received
      extracorporeal membrane oxygenation after thoracic surgery at the University of
      Kentucky from January 9, 2012 to January 9, 2017. Eight patients were identified.
      Results The average time on extracorporeal membrane oxygenation was 9.125 days,
      and the average hospital stay was 65.125 days. Of the 8 patients placed on
      extracorporeal membrane oxygenation, 3 survived to discharge. Of the 3 patients
      who survived to discharge, 1 died within 6 months and 2 have been followed up for
      less than 4 months. The average total charge per patient was calculated to be
      $1,053,551, and the average charge per day was $16,177. The contribution margin
      was $109,200 per case. Conclusions Extracorporeal membrane oxygenation is a tool
      that saves lives in many different patient populations but it does not appear to
      be as effective in patients experiencing acute respiratory distress syndrome
      after thoracic surgery. Extracorporeal membrane oxygenation in this group also
      uses a tremendous amount of hospital resources.

PMID- 29444601
TI  - The role of thoracic surgery in extracorporeal membrane oxygenation services.
AB  - Background Recent evidence surrounding the use of venovenous extracorporeal
      membrane oxygenation in treating acute respiratory failure has led to the
      expansion of extracorporeal membrane oxygenation services worldwide. The high
      rate of complications related to venovenous extracorporeal membrane oxygenation
      often requires intervention by specialist thoracic surgeons. This study aimed to
      investigate the role of specialist thoracic surgeons within the multidisciplinary
      team managing these high-risk patients. Methods We retrospectively reviewed 90
      patients who received venovenous extracorporeal membrane oxygenation at our
      tertiary referral center between December 2011 and May 2015. Four patients who
      underwent lung transplantation were excluded. Results We found that 29.1% (25/86)
      of patients on venovenous extracorporeal membrane oxygenation had undergone a
      thoracic intervention. A total of 82 interventions were performed: 11
      thoracotomies, 49 chest drains, 13 rigid bronchoscopies, 4 flexible
      bronchoscopies, 4 temporary endobronchial blockers, and 1 sternotomy. Of the 11
      thoracotomies, 3 were reexplorations. Survival to discharge for patients who
      underwent thoracic surgical interventions was 72% (18/25). Conclusions Our
      experience has demonstrated that a large proportion of patients receiving
      venovenous extracorporeal membrane oxygenation require a thoracic intervention,
      many of which are major intraoperative procedures. Patients on venovenous
      extracorporeal membrane oxygenation have benefited from rapid on-site access to
      thoracic surgical services to manage these challenging life-threatening
      complications.

PMID- 29444602
TI  - Evaluating Integrative Cancer Clinics With the Claim Assessment Profile: An
      Example With the InspireHealth Clinic.
AB  - BACKGROUND: The evaluation of freestanding integrative cancer clinical programs
      is challenging and is rarely done. We have developed an approach called the Claim
      Assessment Profile (CAP) to identify whether evaluation of a practice is
      justified, feasible, and likely to provide useful information. OBJECTIVES: A CAP
      was performed in order to (1) clarify the healing claims at InspireHealth, an
      integrative oncology treatment program, by defining the most important impacts on
      its clients; (2) gather information about current research capacity at the
      clinic; and (3) create a program theory and path model for use in prospective
      research. STUDY DESIGN/METHODS: This case study design incorporates methods from
      a variety of rapid assessment approaches. Procedures included site visits to
      observe the program, structured qualitative interviews with 26 providers and
      staff, surveys to capture descriptive data about the program, and observational
      data on program implementation. RESULTS: The InspireHealth program is a well
      established, multi-site, thriving integrative oncology clinical practice that
      focuses on patient support, motivation, and health behavior engagement. It
      delivers patient-centered care via a standardized treatment protocol. There
      arehigh levels of research interest from staff and resources by which to conduct
      research. CONCLUSIONS: This analysis provides the primary descriptive and claims
      clarification of an integrative oncology treatment program, an evaluation
      readiness report, a detailed logic model explicating program theory, and a
      clinical outcomes path model for conducting prospective research. Prospective
      evaluation of this program would be feasible and valuable, adding to our
      knowledge base of integrative cancer therapies.

PMID- 29444603
TI  - Safety of Combined Treatment With Monoclonal Antibodies and Viscum album L
      Preparations.
AB  - Combination strategies involving chemotherapy and monoclonal antibodies (mAb) are
      commonly used in attempts to produce better clinical outcomes. This practice has
      led to new and ongoing toxicities that may lead to reductions in dose or
      noncompliance, limiting the effectiveness of treatment. Viscum album L (VA)
      preparations are widely used in Europe as additive therapy and have been
      associated with reduced chemotherapy-related adverse reactions and increased
      health-related quality of life. Concomitant VA therapy might also reduce toxicity
      related to mAb. This retrospective study investigated the safety of combined
      treatment with VA and mAb in cancer patients. A total of 43 patients had combined
      therapy (474 exposures); 12 had VA without mAb (129 exposures), and 8 had mAb
      without VA (68 exposures). Most patients (89.3%) received concomitant
      chemotherapy or supportive therapies. A total of 34 patients (60.7%) experienced
      142 adverse events (AEs). Leucopenia (14.1% of all events), acneiform rash
      (8.5%), and stomatitis (6.3%) occurred most frequently. Longitudinal logistic
      regression analysis suggested a nearly 5 times higher odds of experiencing an AE
      following treatment with mAb compared with mAb plus VA (95% CI = 1.53-16.14). Our
      results, together with theoretical consideration of potential botanical-drug
      interactions, suggest that combined treatment with VA and mAb is safe.

PMID- 29444604
TI  - The Circadian System and Cancer: It's About Time!

PMID- 29444605
TI  - Anxious attachment and excessive acquisition: The mediating roles of
      anthropomorphism and distress intolerance.
AB  - Background and aims Most individuals with hoarding disorder (HD) are prone to
      excessively acquiring new possessions. Understanding the factors that contribute
      to this collecting behavior will allow us to develop better treatment approaches
      for HD. The aim of this study was to test our assumption that an anxious
      attachment style is associated with a tendency to anthropomorphize comforting
      objects and an inability to tolerate distress, which in turn leads to excessive
      acquisition. Methods A total of 361 participants with subclinical to clinical
      acquisition problems (77.8% female) completed a series of self-report measures.
      Results As expected, greater anxious attachment was related to greater distress
      intolerance and stronger tendencies to anthropomorphize inanimate objects. In
      turn, greater distress intolerance and anthropomorphism were related to more
      excessive buying and greater acquisition of free items. Examination of the
      pathways and indirect effects showed support for double mediation rather than
      serial mediation, as distress intolerance did not predict anthropomorphism.
      Discussion and conclusion These novel findings, if replicated, suggest that
      adding treatment modules that target improving distress tolerance and reducing
      anthropomorphism to standard treatment for HD may lead to further reductions in
      excessive acquiring.

PMID- 29444606
TI  - The links between healthy, problematic, and addicted Internet use regarding
      comorbidities and self-concept-related characteristics.
AB  - Background Addicted Internet users present with higher rates of comorbidities,
      e.g., attention-deficit hyperactivity disorder (ADHD), depressive, and anxiety
      disorders. In addition, deficits in self-concept-related characteristics were
      found in addicted Internet gamers and social network users. The aim of this study
      was to examine the links between healthy, problematic, and addicted Internet use
      regarding comorbidities and self-concept-related characteristics. The association
      between recently developed ADHD-like symptoms without an underlying diagnosis and
      addictive Internet use was also examined. Methods n = 79 healthy controls, n = 35
      problematic, and n = 93 addicted Internet users were assessed for comorbidities,
      social and emotional competencies, body image, self-esteem, and perceived stress.
      Apart from an ADHD-diagnosis, recently developed ADHD-like symptoms were also
      assessed. Results Addicted users showed more self-concept-related deficits and
      higher rates of comorbidities with ADHD, depressive, and anxiety disorders.
      Addicted and problematic users showed similarities in the prevalence of cluster B
      personality disorders and decreased levels of characteristics related to
      emotional intelligence. Participants with recently developed ADHD-like symptoms
      scored higher in lifetime and current severity of Internet use compared with
      those without ADHD symptoms. Addicted participants with recently developed ADHD
      symptoms showed higher lifetime Internet use severity compared with those without
      any symptoms. Conclusions Our findings indicate that cluster B personality
      disorders and premorbid problems in emotional intelligence might present a link
      between problematic and addictive Internet use. Furthermore, the findings provide
      a first indication that addictive Internet use is related to ADHD-like symptoms.
      Symptoms of ADHD should therefore be assessed against the background of possible
      addicted Internet use.

PMID- 29444608
TI  - Acute autoimmune myocarditis and hepatitis due to ipilimumab monotherapy for
      malignant melanoma.
AB  - An important agent in melanoma therapy, ipilimumab is associated with autoimmune
      toxicity. Two cases of autoimmune pericarditis and large pericardial effusion
      have been documented with its use. Reports of myocardial toxicity have surfaced
      with this agent, mainly when used in combination with PD1 blockade. We present
      herein a case of autoimmune myocarditis leading to biventricular failure after
      four doses of IV ipilimumab 3 mg/kg as a single agent. Furthermore, this toxic
      effect may be anticipated with PD1 inhibitors. Increased clinical suspicion,
      prompt diagnosis, and steroid therapy are crucial to ensure a favorable clinical
      outcome.

PMID- 29444607
TI  - Psychometric evaluation of Persian Nomophobia Questionnaire: Differential item
      functioning and measurement invariance across gender.
AB  - Background and aims Research examining problematic mobile phone use has increased
      markedly over the past 5 years and has been related to "no mobile phone phobia"
      (so-called nomophobia). The 20-item Nomophobia Questionnaire (NMP-Q) is the only
      instrument that assesses nomophobia with an underlying theoretical structure and
      robust psychometric testing. This study aimed to confirm the construct validity
      of the Persian NMP-Q using Rasch and confirmatory factor analysis (CFA) models.
      Methods After ensuring the linguistic validity, Rasch models were used to examine
      the unidimensionality of each Persian NMP-Q factor among 3,216 Iranian
      adolescents and CFAs were used to confirm its four-factor structure. Differential
      item functioning (DIF) and multigroup CFA were used to examine whether males and
      females interpreted the NMP-Q similarly, including item content and NMP-Q
      structure. Results Each factor was unidimensional according to the Rach findings,
      and the four-factor structure was supported by CFA. Two items did not quite fit
      the Rasch models (Item 14: "I would be nervous because I could not know if
      someone had tried to get a hold of me;" Item 9: "If I could not check my
      smartphone for a while, I would feel a desire to check it"). No DIF items were
      found across gender and measurement invariance was supported in multigroup CFA
      across gender. Conclusions Due to the satisfactory psychometric properties, it is
      concluded that the Persian NMP-Q can be used to assess nomophobia among
      adolescents. Moreover, NMP-Q users may compare its scores between genders in the
      knowledge that there are no score differences contributed by different
      understandings of NMP-Q items.

PMID- 29444609
TI  - Optimization of resources by drug management: A multicentred web-administered
      study on the use of ipilimumab in Italy.
AB  - Objective In a scenario of new expensive cancer therapies entering the market,
      strategies of optimisation and cost containment are crucial in oncology care.
      Better management of drug waste and centralization of drug preparation can be
      effective strategies to achieve these goals. The aim of this work is to describe
      the economic management of a high cost anticancer drug (ipilimumab) in some
      Italian reference centres. Methods This was an observational, multicentred study
      in which economical and clinical data of 21 cancer centres (418 patients) were
      collected during the enrollment period from February 2013 to August 2014. The
      follow-up period ended in July 2015. Results Participants purchased 10.7% more
      vials of ipilimumab than necessary for compounding. The results were variable
      among centres, and only five centres had a deviation lower than 5% between the
      drug purchased and the drug prescribed. Hospitals applying the drug day reached a
      statistically significant residual of drug effectively used compared to the
      amount prescribed (P = 0.018). Consequently, the price for treating a model
      patient was significantly lower in those hospitals (median spare of 7456 euro per
      patient). Conclusions This study demonstrated that the careful management of drug
      waste and the application of drug-day, through a proper selection of vial and the
      ability to use the leftover drug, can generate economic savings. However,
      tailoring the drug stock to clinical need is still an open issue which deserves
      further analysis.

PMID- 29444610
TI  - Evaluation of adherence to Mediterranean diet in medical students at Kocaeli
      University, Turkey.
AB  - Introduction This study was conducted to evaluate the eating habits of medical
      students at Kocaeli University in northwest Turkey in terms of their ability to
      apply their academic knowledge regarding healthy lifestyles to their own lives
      using the Mediterranean Diet Quality Index (KIDMED). Methods In this cross
      sectional study, a questionnaire including demographic information and the KIDMED
      index was administered to 354 medical school students (206 first-year and 148
      third-year students). The students' sex, body mass index, KIDMED score, place of
      residence, smoking habit, media screen time, and regular exercising variables
      were evaluated. Results The KIDMED score was -2 to 8 (3.8 +/- 1.9) among all
      students, -1 to 8 (3.9 +/- 2.0) among first-year students, and -1 to 8 (3.6 +/-
      1.9) among third-year students. In total, 59.1% of females and 40.9% of males
      among first-year students showed moderate adherence to the Mediterranean diet,
      and female students showed better adherence to the Mediterranean diet than males
      among third-year students. Conclusion Medical students at Kocaeli University in
      Turkey showed inadequate application of their academic knowledge about healthy
      living to their own lives.

PMID- 29444611
TI  - The Effect of Goreisan on the Prevention of Chronic Subdural Hematoma Recurrence:
      Multi-Center Randomized Controlled Study.
AB  - The relatively high rate of post-operative recurrence in the treatment of chronic
      subdural hematoma (CSDH) is a significant problem. Goreisan is an herbal medicine
      that exhibits a hydragogue effect by inhibiting the expression of aquaporins, and
      its efficacy in preventing post-operative CSDH recurrence has been suggested by
      several case trials. This multi-center prospective randomized controlled trial
      was performed to investigate the preventative effect of goreisan on post
      operative CSDH recurrence. Patients with symptomatic CSDH over 60 years old
      undergoing burr hole surgery were enrolled in this study. The patients were
      randomly allocated to the control group or the goreisan group, in which oral
      administration of goreisan (7.5 g daily) was continued for 12 weeks. The primary
      end-point was the post-operative recurrence rate at 12 weeks and the secondary
      end-point was hematoma volume reduction rates on computed tomography scan at 12
      weeks. The analyses were performed not only on patients of all ages older than 60
      years, but also on patients divided into those over or under 75 years old. One
      hundred and eighty patients were followed and analyzed (the control group, n =
      88; the goreisan group, n = 92). The recurrence rates considering patients of all
      ages and patients under 75 years old were relatively low in the goreisan group
      but without a significant difference. The hematoma volume reduction rates showed
      no significant difference. Based on the results of the present study, a larger
      scale study including more cases is necessary in future to confirm the efficacy
      of goreisan.

PMID- 29444612
TI  - Circadian Clock Synchronization of the Cell Cycle in Zebrafish Occurs through a
      Gating Mechanism Rather Than a Period-phase Locking Process.
AB  - Studies from a number of model systems have shown that the circadian clock
      controls expression of key cell cycle checkpoints, thus providing permissive or
      inhibitory windows in which specific cell cycle events can occur. However, a
      major question remains: Is the clock actually regulating the cell cycle through
      such a gating mechanism or, alternatively, is there a coupling process that
      controls the speed of cell cycle progression? Using our light-responsive
      zebrafish cell lines, we address this issue directly by synchronizing the cell
      cycle in culture simply by changing the entraining light-dark (LD) cycle in the
      incubator without the need for pharmacological intervention. Our results show
      that the cell cycle rapidly reentrains to a shifted LD cycle within 36 h, with
      changes in p21 expression and subsequent S phase timing occurring within the
      first few hours of resetting. Reentrainment of mitosis appears to lag S phase
      resetting by 1 circadian cycle. The range of entrainment of the zebrafish clock
      to differing LD cycles is large, from 16 to 32 hour periods. We exploited this
      feature to explore cell cycle entrainment at both the population and single cell
      levels. At the population level, cell cycle length is shortened or lengthened
      under corresponding T-cycles, suggesting that a 1:1 coupling mechanism is capable
      of either speeding up or slowing down the cell cycle. However, analysis at the
      single cell level reveals that this, in fact, is not true and that a gating
      mechanism is the fundamental method of timed cell cycle regulation in zebrafish.
      Cell cycle length at the single cell level is virtually unaltered with varying T
      cycles.

PMID- 29444613
TI  - Characteristics and outcomes of patients with intellectual disability admitted to
      a specialist inpatient rehabilitation service.
AB  - Rehabilitation services for people with mental illnesses have been extensively
      researched. However, services with similar aims and specifications for patients
      with intellectual disabilities (IDs) have had little focus. This study describes
      the characteristics and outcomes of 21 patients admitted to a specialist ID
      rehabilitation service over an 8-year time frame. Rather that solely accepting
      'step-down' referrals, some patients were referred from community settings.
      During the study, 20 patients were discharged, 80% to lower levels of service
      restriction, while 14.3% to higher levels. The study suggested that
      rehabilitation services have an important role within the wider service model for
      people with ID. Within the service studied, patients were referred from both
      higher and lower levels of restriction, suggesting the rehabilitation service
      'bridged the gap' between inpatient and community settings, supporting the aim of
      caring for patients in the least restrictive setting for their needs.

PMID- 29444614
TI  - In vitro anti-influenza virus effect of total flavonoid from Trollius ledebouri
      Reichb.
AB  - Objective To investigate the in vitro antivirus effect of total flavonoid from
      Trollius ledebouri Reichb (TFTLR). Methods Madin-Darby canine kidney (MDCK) and
      Human epithelial type 2 (HEp-2) cell lines were used to test the antivirus effect
      of TFTLR on nine virus subtypes: four H1N1, one H3N2, and four other subtypes
      prevalent in North China. Tamiflu, Ribavirin and Lianhua Qingwen were used as
      active comparators. Comprehensive molecular pathway analyses of TFTLR-H1N1 and
      TFTLR-H3N2 relationships were also conducted. Results TFTLR inhibited MDCK cell
      lesions induced by H1N1 subtypes (A/FM1/1/47, A/Puerto Rico/8/1934 H1N1,
      A1/Tianjin Jinnan/15/2009, and A/Brisbane/59/2007) and by the H3N2
      Brisbane/10/2009 strain. TFTLR inhibitory concentration (IC)50 values against
      these viruses were 0.13, 0.07, 0.06, 0.14, and 0.07 mg/ml, respectively; and
      therapeutic index (TI) values were 8.62, 16.0, 18.67, 8.0, and 16.0,
      respectively. TFTLR showed no effect on parainfluenza virus type 1, herpes
      simplex virus type 1, respiratory syncytial virus, and coxsackie group B virus
      type 4. Pathway analysis revealed possible functional therapeutic mechanisms for
      TFTLR against H1N1 and H3N2 infections. Conclusion TFTLR may represent a
      potential therapeutic agent against influenza A subtypes H1N1 and H3N2 that are
      prevalent in North China, and should be investigated further.

PMID- 29444615
TI  - The mysterious polyamines, the enigmatic Barr body, and lupus: comment on the
      article by Kim et al.
AB  - "Polyamine patterns in plasma of patients with systemic lupus erythematosus and
      fever" by Kim et al. provides insight into possible involvement of polyamines in
      systemic lupus erythematosus (SLE). The authors report decreases in N1
      acetylspermidine, spermidine, spermine, and N1-acetylcadaverine and increased
      cadaverine in SLE. Polyamine involvement in many cellular processes and their
      unique characteristics (high charge, length, flexibility, and ubiquity) give
      polyamines importance in health and disease. In this editorial, I describe a
      scenario, the "X chromosome-nucleolus nexus" hypothesis, in which polyamines
      could initially rise because of cellular stress. This rise in polyamines
      increases nucleolar size and activity. Polyamines are critical in the nucleolar
      assembly of ribonucleoprotein complexes, such as ribosomes. However, the
      expanding nucleolus could disrupt a neighboring inactive X chromosome (Barr
      body). This disruption opens additional polyamine genes that alter polyamine
      levels and types through wasteful synthesis and recycling of polyamines. This
      could include a decrease in the key polyamines spermidine and spermine, which are
      critical to nucleolar functioning. And this can decrease S-adenosylmethionine
      needed for cellular methylation leading to hypomethylation seen in SLE. As a
      result, the nucleolus can no longer respond properly to future stresses. With
      altered polyamine levels and types in the nucleolus, many RNA transcripts,
      proteins, and ribonucleoprotein complexes assembled in the nucleolus may be
      trapped in autoantigenic conformations. Many of the major autoantigens in SLE
      are, at least transiently, components of the nucleolus. Therefore, the
      observations of decreased polyamines reported by Kim et al. could be important in
      the formation of autoantigens.

PMID- 29444616
TI  - Endovascular treatment of cerebral aneurysm after renal transplantation in
      polycystic kidney disease.
AB  - Background Patients with polycystic kidney disease have a higher prevalence of
      intracranial aneurysms and may progress to renal failure requiring
      transplantation. The endovascular treatment of intracranial aneurysms may improve
      prognosis, since rupture often causes premature death or disability, but the
      nephrotoxicity risk associated with contrast medium must be always considered in
      cases of renal impairment. Methods A 55-year-old female patient with polycystic
      kidney disease and grafted kidney associated with anterior communicant artery
      aneurysm was successfully treated by embolization. Results The renal function
      remained normal after the procedure. To the authors' knowledge, this is the first
      case of endovascular treatment of brain aneurysm in a transplanted patient
      reported in the medical literature. Conclusions The endovascular procedure in
      renal transplant patients is feasible and can be considered to treat this
      population. Further studies and cases are needed to confirm its safety.

PMID- 29444617
TI  - Hemodynamic impingement and the initiation of intracranial side-wall aneurysms.
AB  - Objective The natural history intracranial aneurysms (IA) remains poorly
      understood despite significant morbidity and mortality associated with IA
      rupture. Hemodynamic impingement resulting in elevations in wall shear stress and
      wall shear stress gradient (WSSG) has been shown to induce aneurysmal remodeling
      at arterial bifurcations. We investigate the hemodynamic environment specific to
      side-wall pre-aneurysmal vasculature. We hypothesize that fluid impingement and
      secondary flow patterns play a role in side-wall aneurysm initiation. Methods
      Eight side-wall internal carotid artery aneurysms from the Aneurisk repository
      were identified. Pre-aneurysmal vasculature was algorithmically reconstructed.
      Blood flow was simulated with computational fluid dynamic simulations. An
      indicator of isolated fluid impingement energy was developed by insetting the
      vessel surface and calculating the impinging component of the fluid dynamic
      pressure. Results Isolated fluid impingement was found to be elevated in the area
      of aneurysm initiation in 8/8 cases. The underlying fluid flow for each area of
      initiation was found to harbor secondary flow patterns known as Dean's vortices,
      the result of changes in momentum imparted by bends in the internal carotid
      artery (ICA). Conclusion Isolated fluid impingement and secondary flow patterns
      may play a major role in the initiation of side-wall aneurysm initiation. We are
      unable to determine if this role is through direct or indirect mechanisms but
      hypothesize that elevations in isolated fluid impingement mark areas of cerebral
      vasculature that are at risk for aneurysm initiation. Thus, this indicator
      provides vascular locations to focus future study of side-wall aneurysm
      initiation.

PMID- 29444618
TI  - Pathophysiology of drug induced weight and metabolic effects: findings from an
      RCT in healthy volunteers treated with olanzapine, iloperidone, or placebo.
AB  - Second generation antipsychotics are prescribed for an increasing number of
      psychiatric conditions, despite variable associations with weight gain,
      dyslipidemia, and impaired glucose tolerance. The mechanism(s) of the apparent
      causal relationships between these medications and metabolic effects have been
      inadequately defined and are potentially confounded by genetic risk of mental
      illness, attendant lifestyle, and concomitant medications. Therefore, we
      conducted a study in which 24 healthy volunteers were randomized to olanzapine
      (highly weight-gain liability), iloperidone (less weight-gain liability), or
      placebo treatment for 28 days under double-blind conditions. We hypothesized that
      antipsychotics induce weight gain primarily through increased caloric intake,
      which causes secondary dyslipidemia and insulin resistance. Subjects were
      phenotyped pre- and post-treatment for body weight, adiposity by dual energy X
      ray absorptiometry, energy expenditure by indirect calorimetry, food intake, oral
      glucose tolerance, plasma lipids, glucose, insulin, and other hormones. We found
      significantly increased food intake and body weight but no change in energy
      expenditure in olanzapine-treated subjects, with associated trends towards lipid
      abnormalities and insulin resistance the extent of which were presumably limited
      by the duration of treatment. Iloperidone treatment led to modest non-significant
      and placebo no weightgain, lipid increases and alterations in insulin metabolism.
      We conclude that second generation antipsychotic drugs, as represented by
      olanzapine, produce their weight and metabolic effects, predominantly, by
      increasing food intake which leads to weight gain that in turn induces metabolic
      consequences, but also through other direct effects on lipid and glucose
      metabolism independant of food intake and weight gain.

PMID- 29444620
TI  - Differential anxiety-like responses in NOD/ShiLtJ and C57BL/6J mice following
      experimental autoimmune encephalomyelitis induction and oral gavage.
AB  - Oral gavage is commonly used in pre-clinical drug evaluation, but is potentially
      aversive and may induce behavioral effects independent of compounds under
      investigation. This study examined the combined effects of repeated oral gavage
      and disease induction on anxiety-like behavior in the experimental autoimmune
      encephalomyelitis (EAE) model of multiple sclerosis. The C57BL/6J and NOD/ShiLtJ
      EAE variants were exposed to sham-EAE induction or untreated control conditions,
      and either daily oral gavage or home cage conditions. Anxiety-like behavior was
      subsequently assessed in the elevated plus maze. C57BL/6J mice exhibited
      increased anxiety-like behavior, relative to NOD/ShiLtJ mice, in response to
      repeated gavage, whereas sham-EAE induction and repeated gavage were associated
      with increased anxiety-like behavior in NOD/ShiLtJ mice. Thus, exposure to the
      induction procedure and repeated gavage differentially altered subsequent anxiety
      like behavior in the two EAE variants. Future pre-clinical studies should rely on
      prior evaluation of parameters of the experimental design using sham-EAE mice.
      Additionally, less aversive administration routes should be utilized wherever
      possible to ensure that procedures do not distort effects of the therapeutic
      under investigation.

PMID- 29444619
TI  - Clinical Value of Long Noncoding RNA HOTAIR as a Novel Biomarker in Digestive
      Cancers: A Meta-Analysis.
AB  - HOX transcript antisense intergenic RNA has been reported to serve as an
      important prognostic biomarker in several types of cancers. However, the clinical
      value of HOX transcript antisense intergenic RNA in digestive cancers remains
      unclear. Therefore, we tried to investigate the clinical role of expression of
      HOX transcript antisense intergenic RNA as a prognostic indicator in digestive
      cancers by a meta-analysis. Literature collection was performed by searching the
      PubMed, Embase, Web of Science, and Cochrane Library databases (up to October 7,
      2017). A quantitative meta-analysis was conducted to assess the eligible articles
      on the prognostic value of HOX transcript antisense intergenic RNA in digestive
      cancers. The pooled hazard ratios or odds ratios with 95% confidence intervals
      were used to evaluate the association between expression of HOX transcript
      antisense intergenic RNA and clinical outcomes. A total of 1844 patients from 22
      studies were included in this meta-analysis. The results found a significant
      association between expression of HOX transcript antisense intergenic RNA and
      poor overall survival in digestive cancers (pooled hazard ratio = 2.19, 95%
      confidence interval, 1.86-2.57, P < .001). Furthermore, subgroup analysis showed
      that tumor type, region, Newcastle-Ottawa scale, and sample size did not alter
      the predictive value of HOX transcript antisense intergenic RNA as an independent
      factor for patients' survival. In addition, we also revealed that the
      clinicopathological characteristics such as differentiation, lymph node
      metastasis, tumor node metastasis (TNM) stage, and distant metastasis were
      positively related to expression of HOX transcript antisense intergenic RNA
      digestive cancers. In conclusion, our results suggested high expression of HOX
      transcript antisense intergenic RNA was correlated with poor clinical outcomes
      and may serve as a novel prognostic biomarker for patients with digestive
      cancers.

PMID- 29444621
TI  - Excitotoxicity in the pathogenesis of neurological and psychiatric disorders:
      Therapeutic implications.
AB  - Neurological and psychiatric disorders are leading contributors to the global
      disease burden, having a serious impact on the quality of life of both patients
      and their relatives. Although the molecular events underlying these heterogeneous
      diseases remain poorly understood, some studies have raised the idea of common
      mechanisms involved. In excitotoxicity, there is an excessive activation of
      glutamate receptors by excitatory amino acids, leading to neuronal damage. Thus,
      the excessive release of glutamate can lead to a dysregulation of Ca2+
      homeostasis, triggering the production of free radicals and oxidative stress,
      mitochondrial dysfunction and eventually cell death. Although there is a
      consensus in considering excitotoxicity as a hallmark in most neurodegenerative
      diseases, increasing evidence points to the relevant role of this pathological
      mechanism in other illnesses affecting the central nervous system. Consequently,
      antagonists of glutamate receptors are used in current treatments or in clinical
      trials in both neurological and psychiatric disorders. However, drugs modulating
      other aspects of the excitotoxic mechanism could be more beneficial. This review
      discusses how excitotoxicity is involved in the pathogenesis of different
      neurological and psychiatric disorders and the promising strategies targeting the
      excitotoxic insult.

PMID- 29444622
TI  - The Role of Close Relationships in Terror Management: A Systematic Review and
      Research Agenda.
AB  - Terror management theory outlines how humans seek self-esteem and worldview
      validation to manage death-related anxiety. Accumulating evidence reveals that
      close relationships serve a similar role. However, to date, there has been no
      synthesis of the literature that delineates when close relationships buffer
      mortality concerns, under what conditions, on which specific outcomes, and for
      whom. This systematic review presents over two decades of research to address
      these questions. Findings from 73 reviewed studies revealed that close
      relationships serve an important role in buffering death-related anxiety. A range
      of dispositional and situational moderating factors influence either the
      activation or inhibition of relational strivings to manage heightened death
      awareness, the most influential being attachment, gender, and relationship
      contingent self-esteem. These findings were integrated into an overarching model
      that highlights some of the conditions under which mortality salience (MS)
      influences relational outcomes. We conclude by highlighting a range of
      theoretical and methodological concerns to be addressed by future research.

PMID- 29444623
TI  - Interpreting Action Research Arm Test Assessment Scores to Plan Treatment.
AB  - Rasch keyforms can help interpret clinical assessment scores. The Action Research
      Arm Test (ARAT) is a commonly used assessment, yet no keyform currently exists.
      The aim is to provide a keyform for the ARAT and demonstrate how a clinician can
      use the keyform to design optimally challenging rehabilitation sessions.
      Secondary analysis of ARAT data ( n = 122) using confirmatory factor and Rasch
      analyses were used to examine the measurement properties and generate a keyform.
      The item standardized factor loadings were >0.40 (range = 0.82-0.96) and R2
      values were >.60 (range = .65-.96). All items exhibited adequate infit statistics
      with point measure correlations >.60 (range = .72-.97). Person reliability was
      .98, and person separation was 7.07. Item-difficulty measures ranged from -2.78
      logits to 2.64 logits. The ARAT has strong measurement properties, and a keyform
      was provided. We showed how the keyform can be utilized by clinicians to
      interpret scores, set goals, and plan treatment.

PMID- 29444624
TI  - Examining Guided and Directed Cues in Strategy Training and Usual Rehabilitation.
AB  - Therapist approach and feedback during rehabilitation may influence patient
      outcomes. It is unclear how much guided cueing, the approach used in strategy
      training, is present in usual rehabilitation care. We compared the frequency of
      guided and directed cueing in strategy training sessions with cueing in usual
      care occupational and physical therapy. We videotaped strategy training,
      occupational therapy, and physical therapy sessions among 20 patients admitted to
      inpatient rehabilitation after stroke. Using a standardized coding scheme, we
      coded and analyzed frequencies of therapists' cues (guided or directed). The
      proportion of guided cues was significantly higher in strategy training
      intervention (42%) compared with occupational therapy (4%) and physical therapy
      (3%). Preliminary research suggests that guided cueing may be more prevalent in
      strategy training than in usual care. Given that guided cueing provides more
      opportunity for patients to take an active role in their rehabilitation, guided
      cueing may lead to superior outcomes.

PMID- 29444625
TI  - Brazilian Photographic Figure Rating Scale for Men: Psychometric Investigation.
AB  - As a follow-up to an earlier study from this research group involving women, this
      study examined the reliability and validity of the Brazilian Photographic Figure
      Rating Scale for Men (BPFRS-M) for evaluating men's body perception and
      dissatisfaction. In both versions of the Brazilian Photographic Figure Rating
      Scale (BPFRS), respondents viewed eight photographic images (seven distorted and
      one accurate) of themselves in standard poses and then offered self-ratings. In
      both versions, 10 experts assessed content validity and demonstrated high
      agreement (defined by ratings of 4-5 on a 5-point scale) that BPFRS items
      measured underlying constructs: and experts showed high (>70%) interrater
      agreement. For this version, participants were 149 Brazilian men (Mean = 22.4; SD
      = 2.7 years). Pearson correlations demonstrated convergence between the BPFRS-M
      and two related scales of men's body image. Positive correlations ( p = .0001)
      were found between actual and respondent-perceived body mass index (BMI). Test
      retest and Kappa Index confirmed temporal stability. The BPFRS-M can accurately
      and reliably assess body perception and dissatisfaction in young men.

PMID- 29444626
TI  - Experiences of Intimate Partner Violence Victims With Police and the Justice
      System in Canada.
AB  - Legal responses to intimate partner violence (IPV) can determine whether and how
      those exposed to IPV seek help. Understanding the victim's perspective is
      essential to developing policy and practice standards, as well as informing
      professionals working in policing and the justice system. In this survey study,
      we utilized a subset of 2,831 people who reported experiencing IPV to examine (a)
      rates of reporting to the police; (b) experiences with, and perceived helpfulness
      of, police; (c) rates of involvement with the criminal and family law systems,
      including protection orders; and (d) experiences with, and perceived helpfulness
      of, the justice system. Data were analyzed using descriptive statistics for
      closed-ended survey questions and content analysis of text responses. More than
      35% of victims reported a violent incident to the police, and perceptions of
      helpfulness were mixed. Fewer victims were involved with the criminal and family
      law systems, and their satisfaction also varied. Text responses provided insight
      into possible reasons for the variability found in experiences, for example, the
      proposed role of victim and system expectations, and respondents' perception that
      getting help depends on "being lucky" with the officials encountered.

PMID- 29444627
TI  - Beliefs About Sexual Intimate Partner Violence Perpetration Among Adolescents in
      South Africa.
AB  - Sexual intimate partner violence (IPV) is a public health problem worldwide.
      Research regarding beliefs about perpetrating sexual IPV is, however, limited.
      This study investigated attitudes, social influence, and self-efficacy beliefs
      and intentions toward perpetrating sexual IPV among Grade 8 adolescents ( M age =
      13.73, SD = 1.04) in the Western Cape Province of South Africa. The study sample
      was taken from the baseline data of the Promoting sexual and reproductive health
      among adolescents in Southern and Eastern Africa (PREPARE) study, a cluster
      randomized controlled trial. Young adolescents ( N = 2,199), from 42 randomly
      selected high schools, participated in the study and answered a paper-and-pencil
      questionnaire. Multivariate ANOVA were conducted to assess differences in beliefs
      and intention toward perpetrating sexual IPV between boys and girls, and between
      perpetrators and nonperpetrators. Results showed that boys were more frequently
      perpetrators (11.3% vs. 3.2%) and victims (13.6% vs. 6.4%) of sexual IPV than
      girls. Boys' attitudes toward perpetrating sexual IPV were more supportive than
      girls'. Boys perceived their social network to be more likely to think that
      putting pressure on a boyfriend or girlfriend to have sex is okay, and boys had a
      lower self-efficacy to refrain from pressuring a boyfriend or girlfriend to have
      sex compared with girls. Both boys and girls, who have perpetrated sexual IPV,
      had more tolerant attitude, social influence, and self-efficacy beliefs toward
      sexual IPV perpetration, compared with nonperpetrators. Intention not to
      perpetrate sexual IPV did not differ between boys and girls, or between
      perpetrators and nonperpetrators. Our findings suggest that interventions should
      address attitude and social influence beliefs regarding sexual IPV perpetration.
      More attention should be given to sexual IPV perpetration among boys. Given that
      sexual IPV victimization and perpetration are significantly linked, prevention of
      sexual IPV perpetration seems to be of utmost importance.

PMID- 29444628
TI  - Assisting the Investigation of Stranger Rapes: Predicting the Criminal Record of
      U.K. Stranger Rapists From Their Crime Scene Behaviors.
AB  - Davies, Wittebrood, and Jackson (1997) were among the first to investigate
      whether offense behaviors are predictive of criminal history, with the findings
      of their paper then utilized by the National Crime Agency (NCA) Behavioral
      Investigative Advisors (BIAs) when assisting rape investigations. The aim of the
      study was to replicate this seminal paper with a larger contemporary sample of
      U.K. stranger rapists as identified by NCA. Data from 474 adult male stranger
      rapists were obtained in relation to 22 crime scene behaviors and nine
      preconviction variables. Results indicated significant differences between the
      Davies et al. original data set and this contemporary data set in both the
      behaviors and the preconvictions they displayed. The contemporary sample was
      significantly less likely to use sighting precautions, use violence, and take
      fingerprint precautions. This sample was also significantly less likely to have
      any of the preconviction crime types, with the exception of drugs offenses. When
      exploring the current data set of stranger rapists, statistical analyses
      indicated a number of key offense behaviors that were able to predict the
      criminal history of stranger rapists. However, contrary to previous research, no
      behaviors were found to be associated with sexual offense preconvictions. The
      results highlight that behaviors and characteristics of stranger sex offenders
      have changed since the 1990s. The implications for practice are discussed.

PMID- 29444629
TI  - Canine Clitoral Carcinoma: A Clinical, Cytologic, Histopathologic,
      Immunohistochemical, and Ultrastructural Study.
AB  - Vaginal and vulvar tumors are uncommon in dogs. Knowledge of canine primary
      clitoral neoplasia is restricted to a few case reports, and only carcinomas have
      been reported. Cytologic and histologic features reported in the literature seem
      to overlap with those of canine apocrine gland anal sac adenocarcinoma (AGASA).
      Clinical features also recall those of canine AGASA, such as locoregional
      metastases and hypercalcemia of malignancy (HM). In this study, 6 cases of
      primary canine clitoral carcinomas (CCCs), with and without HM, were investigated
      by means of cytology, histopathology, electron microscopy, and
      immunohistochemistry for neuroendocrine markers including chromogranin A (CGA),
      synaptophysin (SYN), neuron-specific enolase (NSE), and S-100. In all 6 tumors,
      cytologic findings were consistent with malignant epithelial neoplasia of
      apocrine gland origin. The tumors examined were classified into 3 different
      histological patterns representing different degrees of differentiation: tubular,
      solid, and rosette type. Both CGA and SYN were mildly expressed in 2 of 6 tumors,
      while NSE was consistently expressed in all 6 cases. None of the tumors were S
      100 positive. Transmission electron microscopy revealed electron-dense
      cytoplasmic granules compatible with neuroendocrine granules in all 6 cases. CCCs
      presented clinicopathologic features resembling AGASAs with neuroendocrine
      characteristics, and 2 of 6 neoplasms were considered as carcinomas with
      neuroendocrine differentiation and were positive for 3 neuroendocrine markers.
      CCCs can often present with HM, and long-term outcome is likely poor. Our study
      concludes that CCC seems to be a rare tumor, but it might be underestimated
      because of the overlapping features with AGASA. Further studies should aim to
      define the true incidence of this disease.

PMID- 29444630
TI  - Congenital Ocular Abnormalities in Free-Ranging White-Tailed Deer.
AB  - Congenital ocular abnormalities in cervids have been previously reported as
      individual cases from various regions of the United States and include
      microphthalmia, anophthalmia, congenital cataracts, dermoids, and colobomata. A
      common underlying cause for these abnormalities, such as nutritional
      deficiencies, environmental toxin exposures, or genetic mutations, has not been
      established. This retrospective study summarized and compared cases of suspected
      congenital ocular abnormalities in free-ranging white-tailed deer ( Odocoileus
      virginianus) submitted to the Southeastern Cooperative Wildlife Disease Study
      (SCWDS) in Athens, Georgia, to the preexisting literature. Of 3645 accessions of
      white-tailed deer submitted to SCWDS, 15 qualifying case records were found. An
      additional 15 cases were reported previously in the literature. Conditions
      described in SCWDS cases included microphthalmia (8/15), congenital cataracts
      (3/15), anophthalmia (2/15), colobomata (1/15), anterior segment dysgenesis
      (1/15), ectopic lacrimal gland tissue (1/15), and congenital blindness with
      corneal opacity (1/15). Most (11/15; 73%) of the SCWDS cases were male fawns with
      an average age of 4 months at presentation, consistent with previously described
      cases. Most animals had bilateral abnormalities with few extraocular congenital
      abnormalities, also consistent with existing reports. Cases were variably tested
      for various infectious agents at the time of submission; 2 cases were
      seropositive for bluetongue virus. Spatiotemporal clustering of cases was not
      evident. This study provided a concise and systematic summary of known existing
      cases of congenital ocular defects in fawns but did not identify a cause.

PMID- 29444631
TI  - Accumulation of Laforin and Other Related Proteins in Canine Lafora Disease With
      EPM2B Repeat Expansion.
AB  - Canine Lafora disease (LD) is an autosomal recessive genetic disorder causing
      nonfatal structural epilepsy, mainly affecting miniature wirehaired dachshunds.
      Repeat expansion in the EPM2B gene causes a functional impairment of the
      ubiquitin ligase malin which regulates glycogen metabolism. Abnormally structured
      glycogen accumulates and develop polyglucosan bodies predominantly in the central
      nervous system. The authors performed a comprehensive clinical, genetic, and
      pathological study of 4 LD cases affecting miniature wirehaired dachshund dogs
      with EPM2B repeat expansions, with systemic distribution of polyglucosan bodies
      and accumulation of laforin and other functionally associated proteins in the
      polyglucosan bodies. Myoclonic seizures first appeared at 7-9 years of age, and
      the dogs died at 14-16 years of age. Immunohistochemistry for calbindin revealed
      that the polyglucosan bodies were located in the cell bodies and dendritic
      processes of Purkinje cells. Polyglucosan bodies were also positive for laforin,
      hsp70, alpha/beta-synuclein, ubiquitin, LC3, and p62. Laforin-positive
      polyglucosan bodies were located in neurofilament-positive neurons but not in
      GFAP-positive astrocytes. In nonneural tissues, periodic acid-Schiff (PAS)
      positive polyglucosan bodies were observed in the heart, skeletal muscle, liver,
      apocrine sweat gland, and smooth muscle layer of the urinary bladder. In the
      skeletal muscle, polyglucosan bodies were observed only in type 1 fibers and not
      in type 2 fibers. The results indicate that although the repeat expansion of the
      EPM2B gene is specific to dogs, the immunohistochemical properties of
      polyglucosan body in canine LD are comparable to human LD. However, important
      phenotypic variations exist between the 2 species including the affected skeletal
      muscle fiber type.

PMID- 29444632
TI  - Immunohistochemical Labeling of Multiple Myeloma Oncogene 1/Interferon Regulatory
      Factor 4 (MUM1/IRF-4) in Canine Cutaneous Histiocytoma.
AB  - Multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF-4)
      immunohistochemistry (IHC) is mainly used for diagnostic confirmation of plasma
      cell tumors (PCTs) in dogs and cats. This article describes MUM1/IRF-4 IHC
      expression in 20 cases of canine cutaneous histiocytoma (CH) and compares it with
      10 cutaneous or mucocutaneous PCTs and 5 cutaneous histiocytic sarcomas (HSs)
      submitted to the same IHC protocol. All histiocytomas had strong nuclear and
      variable cytoplasmic immunolabeling for MUM1/IRF-4, whereas all PCTs had strong
      nuclear and moderate cytoplasmic immunolabeling for MUM1/IRF-4. No MUM1/IRF-4
      immunolabeling was detected in the HSs. Although not typically a diagnostic
      challenge, MUM1/IRF-4 expression may have to be used with caution or in
      conjunction with additional immunomarkers to differentiate among poorly
      differentiated round cell tumors, especially when a histiocytic or plasma cell
      origin is suspected.

PMID- 29444633
TI  - Talaromycosis (Penicilliosis) in a Cynomolgus Macaque.
AB  - A sexually mature Chinese-origin female Macaca fascicularis assigned to the high
      dose group in a 26-week toxicology study with an experimental immunomodulatory
      therapeutic antibody (a CD40 L antagonist fusion protein) was euthanized at the
      scheduled terminal sacrifice on study day 192. The animal was healthy at study
      initiation and remained clinically normal throughout the study. On study day 141,
      abnormal clinical pathology changes were found during a scheduled evaluation;
      splenomegaly was detected on study day 149 and supported by ultrasound
      examination. At the scheduled necropsy, there was marked splenomegaly with a
      nodular and discolored appearance. Cytologic examination of a splenic impression
      smear revealed yeast-like organisms within macrophages. Histologically, there was
      disseminated systemic granulomatous inflammation with 2- to 3-MUm oval,
      intracytoplasmic yeast-like organisms in multiple organs identified as
      Talaromyces (Penicillium) marneffei. This organism, not previously reported as a
      pathogen in macaques, causes an important opportunistic infection in
      immunosuppressed humans in specific global geographic locations.

PMID- 29444634
TI  - Evaluation of reaction gap-filling accuracy by randomization.
AB  - BACKGROUND: Completion of genome-scale flux-balance models using computational
      reaction gap-filling is a widely used approach, but its accuracy is not well
      known. RESULTS: We report on computational experiments of reaction gap filling in
      which we generated degraded versions of the EcoCyc-20.0-GEM model by randomly
      removing flux-carrying reactions from a growing model. We gap-filled the degraded
      models and compared the resulting gap-filled models with the original model. Gap
      filling was performed by the Pathway Tools MetaFlux software using its General
      Development Mode (GenDev) and its Fast Development Mode (FastDev). We explored 12
      GenDev variants including two linear solvers (SCIP and CPLEX) for solving the
      Mixed Integer Linear Programming (MILP) problems for gap filling; three different
      sets of linear constraints were applied; and two MILP methods were implemented.
      We compared these 13 variants according to accuracy, speed, and amount of
      information returned to the user. CONCLUSIONS: We observed large variation among
      the performance of the 13 gap-filling variants. Although no variant was best in
      all dimensions, we found one variant that was fast, accurate, and returned more
      information to the user. Some gap-filling variants were inaccurate, producing
      solutions that were non-minimum or invalid (did not enable model growth). The
      best GenDev variant showed a best average precision of 87% and a best average
      recall of 61%. FastDev showed an average precision of 71% and an average recall
      of 59%. Thus, using the most accurate variant, approximately 13% of the gap
      filled reactions were incorrect (were not the reactions removed from the model),
      and 39% of gap-filled reactions were not found, suggesting that curation is still
      an important aspect of metabolic-model development.

PMID- 29444635
TI  - Diel pattern of circadian clock and storage protein gene expression in leaves and
      during seed filling in cowpea (Vigna unguiculata).
AB  - BACKGROUND: Cowpea (Vigna unguiculata) is an important source of protein supply
      for animal and human nutrition. The major storage globulins VICILIN and LEGUMIN
      (LEG) are synthesized from several genes including LEGA, LEGB, LEGJ and CVC
      (CONVICILIN). The current hypothesis is that the plant circadian core clock genes
      are conserved in a wide array of species and that primary metabolism is to a
      large extent controlled by the plant circadian clock. Our aim was to investigate
      a possible link between gene expression of storage proteins and the circadian
      clock. RESULTS: We identified cowpea orthologues of the core clock genes VunLHY,
      VunTOC1, VunGI and VunELF3, the protein storage genes VunLEG, VunLEGJ, and VunCVC
      as well as nine candidate reference genes used in RT-PCR. ELONGATION FACTOR 1-A
      (ELF1A) resulted the most suitable reference gene. The clock genes VunELF3,
      VunGI, VunTOC1 and VunLHY showed a rhythmic expression profile in leaves with a
      typical evening/night and morning/midday phased expression. The diel patterns
      were not completely robust and only VungGI and VungELF3 retained a rhythmic
      pattern under free running conditions of darkness. Under field conditions,
      rhythmicity and phasing apparently faded during early pod and seed development
      and was regained in ripening pods for VunTOC1 and VunLHY. Mature seeds showed a
      rhythmic expression of VunGI resembling leaf tissue under controlled growth
      chamber conditions. Comparing time windows during developmental stages we found
      that VunCVC and VunLEG were significantly down regulated during the night in
      mature pods as compared to intermediate ripe pods, while changes in seeds were
      non-significant due to high variance. The rhythmic expression under field
      conditions was lost under growth chamber conditions. CONCLUSIONS: The core clock
      gene network is conserved in cowpea leaves showing a robust diel expression
      pattern except VunELF3 under growth chamber conditions. There appears to be a
      clock transcriptional reprogramming in pods and seeds compared to leaves. Storage
      protein deposition may be circadian regulated under field conditions but the
      strong environmental signals are not met under artificial growth conditions. Diel
      expression pattern in field conditions may result in better usage of energy for
      protein storage.

PMID- 29444636
TI  - Transcriptome analysis of different growth stages of Aspergillus oryzae reveals
      dynamic changes of distinct classes of genes during growth.
AB  - BACKGROUND: The gene expression profile and metabolic pathways of Aspergillus
      oryzae underlying the anatomical and morphological differentiation across
      different growth stages have not been fully characterized. The rapid development
      of next-generation sequencing technologies provides advanced knowledge of the
      genomic organization of A. oryzae. RESULTS: In this study, we characterized the
      growth and development of A. oryzae at different growth stages, including the
      adaptive phase, logarithmic phase, and stationary phase. Our results revealed
      that A. oryzae undergoes physiological and morphological differentiation across
      the different stages. RNA-seq was employed to analyze the three stages of A.
      oryzae, which generated more than 27 million high-quality reads per sample. The
      analysis of differential gene expression showed more genes expressed
      differentially upon transition from the adaptive phase to the logarithmic and
      stationary phases, while relatively steady trend was observed during the
      transition from the logarithmic phase to the stationary phase. GO classification
      of the differentially expressed genes among different growth stages revealed that
      most of these genes were enriched for single-organism process, metabolic process,
      and catalytic activity. These genes were then subjected to a clustering analysis.
      The results showed that the cluster with the majority of genes with increased
      expression upon transition from the adaptive phase to the logarithmic phase, and
      steady expression from the logarithmic phase to the stationary phase was mainly
      involved in the carbohydrate and amino acid metabolism. CONCLUSION: Our results
      provide a foundation for identifying developmentally important genes and
      understanding the biological processes across various growth stages.

PMID- 29444637
TI  - Estimated assessment of cumulative dietary exposure to organophosphorus residues
      from tea infusion in China.
AB  - BACKGROUND: China has the world's largest tea plantation area in the world. To
      sustain high yields of the tea, multiple pesticides are used on tea crops to
      control pests. Organophosphorus (OP) pesticides are among the most widely used
      types of agricultural pesticides in China. As tea is a significant potential
      source of exposure to pesticide residues, the public concern has increased in
      relation to pesticide residues found in tea in China. The aim of the study was to
      estimate cumulative dietary exposure to OP residues from tea infusion for Chinese
      tea consumers to determine whether exposure to OP residues from tea infusion is a
      cause of health concern for tea consumers in China. METHODS: OP residue data were
      obtained from the China National Monitoring Program on Food Safety (2013-2014),
      encompassing 1687 tea samples from 12 provinces. Tea consumption data were
      obtained from the China National Nutrient and Health Survey (2002), comprising
      506 tea consumers aged 15-82 years. The transfer rates of residues from tea
      leaves into tea infusions were obtained from the literature. The relative potency
      factor (RPF) approach was used to estimate acute cumulative exposure to 20 OP
      residues from tea infusion using methamidophos as the index compound. Dietary
      exposure was calculated in a probabilistic way. RESULTS: For tea consumers, the
      mean and the 99.9th percentile (P99.9) of cumulative dietary exposure to OP
      residues from tea infusion equalled 0.08 and 1.08 MUg/kg bw/d. When compared with
      the acute reference dose (ARfD), 10 MUg/kg bw/d for methamidophos, this accounts
      for 0.8 and 10.8% of the ARfD. CONCLUSIONS: Even when considering OP residues
      from vegetables, fruits and other foods, there are no health concerns based on
      acute dietary exposure to OP residues from tea infusion. However, it is necessary
      to strengthen the management of the OP pesticides used on tea in China to reduce
      the risk of chronic dietary exposure to OPs from tea infusion.

PMID- 29444638
TI  - Unusual elevation in Entropy but not in PSI during general anesthesia: a case
      report.
AB  - BACKGROUND: EEG monitoring is useful for determining an adequate level of
      anesthesia. However it is sometimes interfered by various reasons. We describe a
      case in which we successfully confirmed the adequate depth of anesthesia by
      monitoring the patient state index (PSI), which was computed from the SedLine
      monitor data in Root (Masimo) during general anesthesia. Our case showed unusual
      elevations in entropy, but not in PSI. CASE PRESENTATION: A 34-year-old woman was
      scheduled for emergency surgery for a left tibial open fracture and a right
      femoral closed fracture, which were sustained during a traffic accident. Forty
      five minutes after intubation, the response entropy abruptly increased up to 100
      and state entropy to 91. Despite the absence of other abnormal events, the
      entropy data led to two types of incorrect decisions. The first was owing to the
      effect of the EMG and the second was misleading during the surgeon's hammering.
      However, PSI from the SedLine monitor seemed to be less influenced by the same
      events. CONCLUSIONS: In this report, we suggest that the PSI, derived from new
      generation SedLine (Root, Masimo) may be a useful parameter for clinically
      determining the level of sedation. The use of two monitoring devices with
      different EEG algorithms might be helpful for determining the anesthetic depth
      and making decisions.

PMID- 29444639
TI  - Differential expression of mRNA isoforms in the skeletal muscle of pigs with
      distinct growth and fatness profiles.
AB  - BACKGROUND: The identification of genes differentially expressed in the skeletal
      muscle of pigs displaying distinct growth and fatness profiles might contribute
      to identify the genetic factors that influence the phenotypic variation of such
      traits. So far, the majority of porcine transcriptomic studies have investigated
      differences in gene expression at a global scale rather than at the mRNA isoform
      level. In the current work, we have investigated the differential expression of
      mRNA isoforms in the gluteus medius (GM) muscle of 52 Duroc HIGH (increased
      backfat thickness, intramuscular fat and saturated and monounsaturated fatty
      acids contents) and LOW pigs (opposite phenotype, with an increased
      polyunsaturated fatty acids content). RESULTS: Our analysis revealed that 10.9%
      of genes expressed in the GM muscle generate alternative mRNA isoforms, with an
      average of 2.9 transcripts per gene. By using two different pipelines, one based
      on the CLC Genomics Workbench and another one on the STAR, RSEM and DESeq2
      softwares, we have identified 10 mRNA isoforms that both pipelines categorize as
      differentially expressed in HIGH vs LOW pigs (P-value < 0.01 and +/-0.6 log2fold
      change). Only five mRNA isoforms, produced by the ITGA5, SEMA4D, LITAF, TIMP1 and
      ANXA2 genes, remain significant after correction for multiple testing (q-value <
      0.05 and +/-0.6 log2fold-change), being upregulated in HIGH pigs. CONCLUSIONS:
      The increased levels of specific ITGA5, LITAF, TIMP1 and ANXA2 mRNA isoforms in
      HIGH pigs is consistent with reports indicating that the overexpression of these
      four genes is associated with obesity and metabolic disorders in humans. A
      broader knowledge about the functional attributes of these mRNA variants would be
      fundamental to elucidate the consequences of transcript diversity on the
      determinism of porcine phenotypes of economic interest.

PMID- 29444640
TI  - Cancer screening in Koreans: a focus group approach.
AB  - BACKGROUND: Cancer is the greatest disease burden in Korea. Cancer screening can
      reduce the burden of cancer but cancer screening rates among Koreans remain low.
      The purposes of this study were to a) understand Koreans' beliefs and knowledge
      about cancer screening, and b) explore preferred strategies for increasing cancer
      screening utilization. METHODS: We conducted a descriptive, qualitative study
      using eight face-to-face focus groups with a total of 64 Koreans aged 40 and
      over. Participants answered semi-structured, open-ended questions assessing their
      experiences with, and beliefs, knowledge, and opinions about, cancer screening.
      All interview data were recorded and analyzed in the context of the health belief
      model (HBM). RESULTS: The most important themes that emerged from the focus group
      data were (a) perceived susceptibility (most of the participants believed they
      were not susceptible to cancer; those who perceived themselves susceptible to
      cancer were reluctant to express it); (b) perceived benefits (early detection and
      feelings of relief after cancer screening were benefits; participants had
      screening because they wanted to take advantage of the Korean government's
      Medical Payment Support program for cancer patients who have participated in the
      National Cancer Screening program); (c) perceived barriers (no symptoms; self
      care when having symptoms; widespread distrust of tests, doctors, and hospitals;
      unkind health care providers; the financial burdens of advanced cancer screening
      tests; and the discomfort during cancer screening); and (d) knowledge of the
      causes of cancer (incorrect knowledge including beliefs that stress, personality,
      and body overuse cause cancer). Almost all of the participants were very
      knowledgeable about the seriousness of cancer and were confident that they were
      able to have cancer screening. Participants preferred strategies of cancer
      screening using group interventions with family or friends; various information
      delivery methods; information emphasizing the importance of cancer prevention;
      convenient, free, or inexpensive services; and kind health care providers.
      CONCLUSIONS: This HBM-based research suggests that beliefs in low susceptibility
      to cancer, many barriers to cancer screening, and incorrect knowledge should be
      the foci for increasing cancer screening rates in Koreans. Interventions could
      change individual cultural beliefs and increase knowledge as well as the quality
      of health care for Koreans.

PMID- 29444641
TI  - Oasis 2: improved online analysis of small RNA-seq data.
AB  - BACKGROUND: Small RNA molecules play important roles in many biological processes
      and their dysregulation or dysfunction can cause disease. The current method of
      choice for genome-wide sRNA expression profiling is deep sequencing. RESULTS:
      Here we present Oasis 2, which is a new main release of the Oasis web application
      for the detection, differential expression, and classification of small RNAs in
      deep sequencing data. Compared to its predecessor Oasis, Oasis 2 features a novel
      and speed-optimized sRNA detection module that supports the identification of
      small RNAs in any organism with higher accuracy. Next to the improved detection
      of small RNAs in a target organism, the software now also recognizes potential
      cross-species miRNAs and viral and bacterial sRNAs in infected samples. In
      addition, novel miRNAs can now be queried and visualized interactively, providing
      essential information for over 700 high-quality miRNA predictions across 14
      organisms. Robust biomarker signatures can now be obtained using the novel
      enhanced classification module. CONCLUSIONS: Oasis 2 enables biologists and
      medical researchers to rapidly analyze and query small RNA deep sequencing data
      with improved precision, recall, and speed, in an interactive and user-friendly
      environment. AVAILABILITY AND IMPLEMENTATION: Oasis 2 is implemented in Java,
      J2EE, mysql, Python, R, PHP and JavaScript. It is freely available at
      https://oasis.dzne.de.

PMID- 29444642
TI  - Income inequality in uptake of voluntary versus organised breast cancer
      screening: evidence from the British Household Panel Survey.
AB  - BACKGROUND: This paper measures income-related inequality in uptake of breast
      cancer screening among women before and after a policy change to extend the
      screening programme to women aged 65 to 70. Prior to programme expansion women
      aged 50 to 64 were invited for screening under the national cancer screening
      programme in England and Wales whereas women in the 65 to 70 age cohort could
      elect to be screened by personally organising a screen. This will give a deeper
      insight into the nature of inequality in screening and the impact of policies
      aimed at widening the access related to age on inequality of uptake. METHODS:
      Taking advantage of this natural experiment, inequality is quantified across the
      different age cohorts and time periods with the use of concentration indices
      (CI). Using data from the British Household Panel Survey, information on
      screening attendance, equivalised household income and age was taken for the
      three years prior to the programme expansion and the three years immediately
      following the policy change. RESULTS: Results show that following the expansion,
      inequality significantly reduced for the 50-64 age group, prior to the expansion
      there was a pro-rich inequality in screening uptake. There is also evidence of a
      reduction in income inequality in screening uptake among those aged 65 to 70 and
      an increase in the number of women attending screening from this older age
      cohort. CONCLUSIONS: This indicates that an organised breast screening programme
      is likely to reduce income related inequality over a screening programme where
      women must organise their own screen. This is important when breast screening is
      one of the main methods used to detect breast cancer at an earlier stage which
      improves outcomes for women and reduces treatment costs.

PMID- 29444643
TI  - Sonographic evaluation of adrenal size in neonates (23 to 41 weeks of gestation).
AB  - BACKGROUND: Fetal adrenal gland size is known to have a positive correlation with
      both gestational age and estimated body weight. In contrast, some clinical
      observations suggest that maturation of the adrenal stress response occurs after
      30 weeks of gestation. In this study, adrenal gland size at birth in extremely
      preterm to term neonates was investigated using ultrasonography to evaluate the
      adrenal developmental pattern and the impact of prematurity and perinatal
      factors. METHODS: The area of the right adrenal gland was measured in the first 3
      h of life in 350 neonates and corrected for birth weight (BW) to determine the
      corrected adrenal area index (cAI). The neonates were subdivided into three
      groups: group 1 (before 30 weeks of gestation), group 2 (30 to 36 weeks), and
      group 3 (after 37 weeks). Differences in the cAI among the 3 groups were compared
      to estimate the impact of perinatal factors. RESULTS: The adrenal gland size was
      measurable in all neonates with gestational age ranging from 23 to 41 weeks.
      Right adrenal gland area was highly correlated with BW (r = 0.75, p < 0.01). cAI
      showed a significant negative correlation with gestational age in group 1 (r = -
      0.67, p < 0.01), whereas it showed no correlation with gestational age in both
      groups 2 and 3. As for the impact of perinatal parameters on cAI, only
      gestational age in group 1 and only fetal distress in group 2 were correlated
      with cAI. In group 3, perinatal parameters such as fetal distress and low Apgar
      score were correlated with cAI. CONCLUSIONS: The present study demonstrated that
      the developmental pattern of fetal adrenal gland was different before and after
      30 weeks of gestation, suggesting that the magnitude of adrenal stress response
      might mature after 30 weeks of gestation.

PMID- 29444644
TI  - Use of esophageal balloon pressure-volume curve analysis to determine esophageal
      wall elastance and calibrate raw esophageal pressure: a bench experiment and
      clinical study.
AB  - BACKGROUND: Accurate measurement of esophageal pressure (Pes) depends on proper
      filling of the balloon. Esophageal wall elastance (Ees) may also influence the
      measurement. We examined the estimation of balloon-surrounding elastance in a
      bench model and investigated a simplified calibrating procedure of Pes in a
      balloon with relatively small volume. METHODS: The Cooper balloon catheter
      (geometric volume of 2.8 ml) was used in the present study. The balloon was
      progressively inflated in different gas-tight glass chambers with different inner
      volumes. Chamber elastance was measured by the fitting of chamber pressure and
      balloon volume. Balloon pressure-volume (P-V) curves were obtained, and the slope
      of the intermediate linear section was defined as the estimated chamber
      elastance. Balloon volume tests were also performed in 40 patients under
      controlled ventilation. The slope of the intermediate linear section on the end
      expiratory esophageal P-V curve was calculated as the Ees. The balloon volume
      with the largest Pes tidal swing was defined as the best volume. Pressure
      generated by the esophageal wall during balloon inflation (Pew) was estimated as
      the product of Ees and best volume. Because the clinical intermediate linear
      section enclosed filling volume of 0.6 to 1.4 ml in each of the patient, we
      simplified the estimation of Ees by only using parameters at these two filling
      volumes. RESULTS: In the bench experiment, bias (lower and upper limits of
      agreement) was 0.5 (0.2 to 0.8) cmH2O/ml between the estimated and measured
      chamber elastance. The intermediate linear section on the clinical and bench P-V
      curves resembled each other. Median (interquartile range) Ees was 3.3 (2.5-4.1)
      cmH2O/ml. Clinical best volume was 1.0 (0.8-1.2) ml and ranged from 0.6 to 1.4
      ml. Estimated Pew at the best volume was 2.8 (2.5-3.5) cmH2O with a maximum value
      of 5.2 cmH2O. Compared with the conventional method, bias (lower and upper limits
      of agreement) of Ees estimated by the simple method was - 0.1 (- 0.7 to 0.6)
      cmH2O/ml. CONCLUSIONS: The slope of the intermediate linear section on the
      balloon P-V curve correlated with the balloon-surrounding elastance. The
      estimation of Ees and calibration of Pes were feasible for a small-volume
      balloon. TRIAL REGISTRATION: Identifier NCT02976844 . Retrospectively registered
      on 29 November 2016.

PMID- 29444645
TI  - How to achieve the desired outcomes of advance care planning in nursing homes: a
      theory of change.
AB  - BACKGROUND: Advance care planning (ACP) has been identified as particularly
      relevant for nursing home residents, but it remains unclear how or under what
      circumstances ACP works and can best be implemented in such settings. We aimed to
      develop a theory that outlines the hypothetical causal pathway of ACP in nursing
      homes, i.e. what changes are expected, by means of which processes and under what
      circumstances. METHODS: The Theory of Change approach is a participatory method
      of programme design and evaluation whose underlying intention is to improve
      understanding of how and why a programme works. It results in a Theory of Change
      map that visually represents how, why and under what circumstances ACP is
      expected to work in nursing home settings in Belgium. Using this approach, we
      integrated the results of two workshops with stakeholders (n = 27) with the
      results of a contextual analysis and a systematic literature review. RESULTS: We
      identified two long-term outcomes that ACP can achieve: to improve the
      correspondence between residents' wishes and the care/treatment they receive and
      to make sure residents and their family feel involved in planning their future
      care and are confident their care will be according to their wishes. Besides
      willingness on the part of nursing home management to implement ACP and act
      accordingly, other necessary preconditions are identified and put in
      chronological order. These preconditions serve as precursors to, or requirements
      for, accomplishing successful ACP. Nine original key intervention components with
      specific rationales are identified at several levels (resident/family, staff or
      nursing home) to target the preconditions: selection of a trainer, ensuring
      engagement by management, training ACP reference persons, in-service education
      for healthcare staff, information for staff, general practitioners, residents and
      their family, ACP conversations and documentation, regular reflection sessions,
      multidisciplinary meetings, and formal monitoring. ONCLUSIONS: The Theory of
      Change map presented here illustrates a theory of how ACP is expected to work in
      order to achieve its desired long-term outcomes while highlighting organisational
      factors that potentially facilitate the implementation and sustainability of ACP.
      We provide the first comprehensive rationale of how ACP is expected to work in
      nursing homes, something that has been called for repeatedly.

PMID- 29444646
TI  - Lack of association between cigarette smoking and Epstein Barr virus reactivation
      in the nasopharynx in people with elevated EBV IgA antibody titres.
AB  - BACKGROUND: Subjects with elevated Epstein-Barr virus (EBV) immunoglobulin A
      (IgA) titers have a higher risk of developing nasopharyngeal carcinoma (NPC),
      indicating that reactivation of EBV in the local mucosa might be important for
      NPC carcinogenesis. Cigarette smoking appears to be one of the environmental risk
      factors for NPC. However, it remains unclear whether smoking-induced
      nasopharyngeal carcinogenesis acts through reactivating EBV in the nasopharyngeal
      mucosa. Therefore, this study aims to investigate the association between
      cigarette smoking and nasopharyngeal EBV reactivation in a NPC high-risk
      population. METHODS: A NPC high-risk cohort study, established from a population
      based NPC screening program of 22,816 subjects, consisted of 1045 subjects with
      elevated serum IgA antibodies against EBV viral capsid antigen (VCA/IgA). Among
      high-risk subjects, information on detailed cigarette smoking history was
      collected among 313 male subjects. The associations between cigarette smoking and
      EBV antibody levels, EBV DNA load of the nasopharynx were analyzed. RESULTS: No
      significant association was observed between either nasopharyngeal EBV DNA load
      or serum VCA/IgA titers and smoking status, age at smoking initiation, daily
      smoking intensity, smoking duration, cigarette type, or pack-years of smoking.
      Cigarette smoking characteristics in all subgroups did not correlate with
      nasopharyngeal EBV DNA positivity or EBV VCA/IgA seropositivity. CONCLUSIONS: In
      a population at high risk of NPC, our study suggests that cigarette smoking is
      neither associated with nasopharyngeal EBV DNA load nor serum VCA/IgA antibody
      level. Smoking-associated NPC carcinogenesis may act through other mechanisms
      than reactivating nasopharyngeal EBV replication.

PMID- 29444647
TI  - Exposure to revised drinking guidelines and 'COM-B' determinants of behaviour
      change: descriptive analysis of a monthly cross-sectional survey in England.
AB  - BACKGROUND: January 2016 saw the publication of proposed revisions to the UK's
      lower risk drinking guidelines but no sustained promotional activity. This paper
      aims to explore the impact of publishing guidelines without sustained promotional
      activity on reported guideline exposure and determinants of behaviour
      (capability, opportunity and motivation) proposed by the COM-B model. METHODS:
      Data were collected by a monthly repeat cross-sectional survey of adults (18+)
      resident in England over 15 months between November 2015 and January 2017 from a
      total of 16,779 drinkers, as part of the Alcohol Toolkit Study. Trends and
      associated 95% confidence intervals were described in the proportion of reported
      exposure to guidelines in the past month and measures of the capability,
      opportunity and motivation to consume alcohol within drinking guidelines.
      RESULTS: There was a rise in reported exposure to drinking guidelines in January
      2016 (57.6-80.6%) which did not reoccur in January 2017. Following the increase
      in January 2016, reported exposure reduced slowly but remained significantly
      higher than in December 2015. In February 2016, there was an increase in measures
      of capability (31.1% reported tracking units of alcohol consumption and 87.8%
      considered it easier to drink safely) and opportunity (84.0% perceived their
      lifestyle as conducive to drinking within guidelines). This change was not
      maintained in subsequent months. Other measures showed marginal changes between
      January and February 2016 with no evidence of change in subsequent months.
      CONCLUSIONS: Following the publication of revised drinking guideline in January
      2016, there was a transient increase in exposure to guidelines, and capability
      and opportunity to drink within the guidelines that diminished over time. The
      transience and size of the changes indicate that behaviour change is unlikely.
      Well-designed, theory-based promotional campaigns may be required for drinking
      guidelines to be an effective public health intervention.

PMID- 29444648
TI  - School and class-level variations and patterns of physical activity: a multilevel
      analysis of Danish high school students.
AB  - BACKGROUND: There is limited knowledge of physical activity (PA) patterns among
      high school students. High schools plays an important role as context for the
      students, but it is uncertain to what extent schools influence student
      participation in PA during leisure time. The purpose of this study is to describe
      patterns of PA and assess variations between schools and classes in PA, in a
      large cohort of Danish high school students. METHODS: Self-reported cross
      sectional data came from The Danish National Youth Study, comprising a total of
      70,674 students attending 119 different schools and 3213 classes. Multilevel
      logistic regressions were applied to evaluate the association between socio
      demographic variables and patterns of PA, and to assess the impact of schools and
      classes on PA measures. RESULTS: Students whose parents have achieved a lower
      level of education, older students and girls of perceived ethnic minority
      generally participated less in several forms of PA during leisure time.
      Substantial variations between schools were observed in terms of participation in
      PA at school during leisure time and in terms of use of active transportation to
      and from school. The school-level accounted for 9% (intra-class correlation
      coefficient (ICC) = 0.09 (95% CI: 0.06-0.11)) and 8% (ICC = 0.08 (95% CI: 0.07
      0.11)) of the variation for participation in PA during leisure time and active
      transportation. CONCLUSION: Overall, students whose parents achieved a lower
      level of education, older students and girls of perceived ethnic minority
      represent vulnerable groups in relation to participation in several forms of PA
      during leisure time. The ICCs indicate that schools, in particular, have the
      potential to influence participation in PA at school during leisure time and
      active transportation to and from school. Thus, high schools should encourage and
      facilitate activities aimed at engaging students in PA during leisure time as
      well as encourage active transportation.

PMID- 29444649
TI  - Patterns of pleural pressure amplitude and respiratory rate changes during
      therapeutic thoracentesis.
AB  - BACKGROUND: Although the impact of therapeutic thoracentesis on lung function and
      blood gases has been evaluated in several studies, some physiological aspects of
      pleural fluid withdrawal remain unknown. The aim of the study was to assess the
      changes in pleural pressure amplitude (Pplampl) during the respiratory cycle and
      respiratory rate (RR) in patients undergoing pleural fluid withdrawal. METHODS:
      The study included 23 patients with symptomatic pleural effusion. Baseline
      pleural pressure curves were registered with a digital electronic manometer.
      Then, the registrations were repeated after the withdrawal of consecutive
      portions of pleural fluid (200 ml up to 1000 ml and 100 ml above 1000 ml). In all
      patients the pleural pressure curves were analyzed in five points, at 0, 25%,
      50%, 75% and 100% of the relative volume of pleural effusion withdrawn in
      particular patients. RESULTS: There were 11 and 12 patients with right sided and
      left sided pleural effusion, respectively (14 M, 9F, median age 68, range 46-85
      years). The most common cause of pleural effusion were malignancies (20 pts.,
      87%). The median total volume of withdrawn pleural fluid was 1800 (IQR 1500-2400)
      ml. After termination of pleural fluid withdrawal Pplampl increased in 22/23
      patients compared to baseline. The median Pplampl increased from 3.4 (2.4-5.9)
      cmH2O to 10.7 (8.1-15.6) cmH2O (p < 0.0001). Three patterns of Pplampl changes
      were identified. Although the patterns of RR changes were more diversified, a
      significant increase between RR at baseline and the last measurement point was
      found (p = 0.0097). CONCLUSIONS: In conclusion, therapeutic thoracentesis is
      associated with significant changes in Pplampl during the respiratory cycle. In
      the vast majority of patients Pplampl increased steadily during pleural fluid
      withdrawal. There was also an increase in RR. The significance of these changes
      should be elucidated in further studies. TRIAL REGISTRATION: ClinicalTrial.gov,
      registration number: NCT02192138 , registration date: July 1st, 2014.

PMID- 29444650
TI  - Designing a behavioral intervention using the COM-B model and the theoretical
      domains framework to promote gas stove use in rural Guatemala: a formative
      research study.
AB  - BACKGROUND: Three billion people use solid cooking fuels, and 4 million people
      die from household air pollution annually. Shifting households to clean fuels,
      like liquefied petroleum gas (LPG), may protect health only if stoves are
      consistently used. Few studies have used an implementation science framework to
      systematically assess "de-implementation" of traditional stoves, and none have
      done so with pregnant women who are more likely to adopt new behaviors. We
      evaluated an introduced LPG stove coupled with a phased behavioral intervention
      to encourage exclusive gas stove use among pregnant women in rural Guatemala.
      METHODS: We enrolled 50 women at < 20 weeks gestation in this prospective cohort
      study. All women received a free 3-burner LPG stove and ten tank refills. We
      conducted formative research using COM-B Model and Theoretical Domains Framework
      (TDF). This included thematic analysis of focus group findings and classes
      delivered to 25 pregnant women (Phase 1). In Phase 2, we complemented classes
      with a home-based tailored behavioral intervention with a different group of 25
      pregnant women. We mapped 35 TDF constructs onto survey questions. To evaluate
      stove use, we placed temperature sensors on wood and gas stoves and estimated
      fraction of stove use three times during pregnancy and twice during the first
      month after infant birth. RESULTS: Class attendance rates were above 92%. We
      discussed feasible ways to reduce HAP exposure, proper stove use, maintenance and
      safety. We addressed food preferences, ease of cooking and time savings through
      cooking demonstrations. In Phase 2, the COM-B framework revealed that other
      household members needed to be involved if the gas stove was to be consistently
      used. Social identity and empowerment were key in decisions about stove repairs
      and LPG tank refills. The seven intervention functions included training,
      education, persuasion, incentivization, modelling, enablement and environmental
      restructuring. Wood stove use dropped upon introduction of the gas stove from 6.4
      h to 1.9 h. CONCLUSIONS: This is the first study using the COM-B Model to develop
      a behavioral intervention that promotes household-level sustained use of LPG
      stoves. This study lays the groundwork for a future LPG stove intervention trial
      coupled with a behavioral change intervention. TRIAL REGISTRATION: NCT02812914,
      registered 3 June 2016, retrospectively registered.

PMID- 29444651
TI  - Perceived health and work-environment related problems and associated subjective
      production loss in an academic population.
AB  - BACKGROUND: The aim was to investigate the prevalence of health problems and work
      environment problems and how these are associated with subjective production loss
      among women and men at an academic workplace. An additional aim was to
      investigate whether there were differences between women and men according to age
      group, years at current workplace, academic rank or managerial position. METHODS:
      A questionnaire was sent in 2011 to all employees at a Swedish university (n =
      5144). Only researchers and teachers were included in the study (n = 3207).
      Spearman correlations were performed to investigate differences in health and
      work environment problems. Employees who reported having experienced work
      environment or health problems in the previous seven days (n = 1475) were
      included in the analyses in order to investigate differences in subjective
      production loss. This was done using Student's t-test, One-way Anova and
      generalized linear models. RESULTS: The response rate was 63% (n = 2022). A total
      of 819 academic staff (40% of the population) reported experiencing either health
      problems, work environment problems or both during the previous seven days. The
      prevalence of health problems only or a combination of work environment and
      health problems was higher among women than men (p-value ?0.05). This was
      especially the case for younger women, those in lower academic positions and
      those who had worked for fewer years at their current workplace. No difference
      was found for work environment problems. The majority of the employees who
      reported problems said that these problems affected their ability to perform at
      work (84-99%). The average production loss varied between 31 and 42% depending on
      the type of problem. Production loss due to health-related and work-environment
      related problems was highest among junior researchers and managers. No
      significant difference between men and women was found in the level of production
      loss. CONCLUSION: Subjective production loss in academia can be associated with
      health and work- environment problems. These losses appear similar for women and
      men even though younger female academics, women in lower academic ranks and those
      with fewer years of employment in their current workplace report a higher
      prevalence of health problems and combined work-environment and health problems
      than men.

PMID- 29444652
TI  - Physical activity and risk of testicular cancer: a systematic review.
AB  - BACKGROUND: Physical activity has been implicated as a risk factor in the
      development of testicular cancer (TC), but the relationship remains
      controversial. This systematic review pooled available evidence regarding this
      association. METHODS: Using Boolean search terms and following PRISMA guidelines,
      we examined the risk of TC across three categories of exposure: intensity (i.e.
      comparison of risk between those previously exposed to high, moderate and low
      levels of physical activity); dose-response (i.e. whether risk of TC increases or
      decreases with increasing exposure to physical activity); and the role of timing
      of physical activity (i.e. during early childhood or adolescence). RESULTS:
      Thirteen studies (11 case-control studies, 2 cohort studies) were included in the
      review. While some studies have reported a strong protective effect of high
      levels of physical activity on risk of TC, others have reported either no
      relationship or a weak direct association; and while a dose-response relationship
      has been identified across several studies, this relationship has been observed
      in both directions. Similarly conflicting results exist in terms of individual
      types of activity and the lifecourse timing of the physical activity. Reasons for
      this inconsistency may include the absence of any association, heterogeneous
      assessment of physical activity, misclassification bias and difference in sample
      sizes. CONCLUSIONS: On balance, there is presently no strong evidence of an
      association between physical activity and risk of subsequent TC. This review
      highlights key areas for future investigation that may clarify any association
      between physical activity and risk of testicular cancer.

PMID- 29444653
TI  - Transarterial chemoembolization (TACE) using mitomycin and lipiodol with or
      without degradable starch microspheres for hepatocellular carcinoma: comparative
      study.
AB  - BACKGROUND: To evaluate survival data and local tumor control after transarterial
      chemoembolization in two groups with different embolization protocols for the
      treatment of HCC patients. METHODS: Ninty-nine patients (mean age: 63.6 years),
      78 male (78.8%) with HCC were repeatedly treated with chemoembolization in 4-week
      intervals. Eighty-eight patients had BCLC-Stage-B and in 11 patients,
      chemoembolization was performed for bridging (BCLC-Stage-A). In total, 667
      chemoembolization treatments were performed (mean 6.7 treatments/patient). The
      administered chemotherapeutic agent included mitomycin. For embolization,
      lipiodol only (n = 51;51.5%; mean age 63.8 years; 38 male), or lipiodol plus
      degradable starch microspheres (DSM) (n = 48; 48.5%; mean age 63.4 years; 40
      male) were used. The local tumor response was assessed by MRI using Response
      Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). Patient survival times were
      evaluated using Kaplan-Meier curves and log-rank tests. RESULTS: The local tumor
      control in the lipiodol-group was: PR (partial response) in 11 (21.6%), SD
      (stable disease) in 32 (62.7%) and PD (progressive disease) in 8 cases (15.7%).
      In the lipiodol-DSM-group, PR was seen in 14 (29.2%), SD in 22 (45.8%), and PD in
      12 (25.0%) individuals (p = 0.211). The median survival of patients after
      chemoembolization with lipiodol was 25 months and in the lipiodol-DSM-group 28
      months (p = 0.845). CONCLUSION: Our data suggest a slight benefit of the use of
      lipiodol and DSM in comparison of using lipiodol only for chemoembolization of
      HCC in terms of local tumor control and survival data, this trend did not reach
      the level of significance.

PMID- 29444654
TI  - The comparison of perceived health-related quality of life between Australian
      children with severe specific language impairment to age and gender-matched
      peers.
AB  - BACKGROUND: Children with specific language impairment often present with
      multiple comorbidities, which may adversely affect both participation in play and
      academic performance, potentially impacting a child's health-related quality of
      life. This study 1) explored the suitability of the Pediatric Quality of Life
      InventoryTM Version 4.0 Generic Core Scales (PedsQLTM) for use with a typically
      developing Australian control group, and 2) compared the health-related quality
      of life between a control group and Australian children with severe specific
      language impairment. METHODS: Health-related quality of life data collected as
      part of a broader study of 43 children with severe specific language impairment
      (males = 35, age range 5-16, mean age = 8.79+/- 2.92) enrolled at a special
      school were used to explore previously unreported findings. Typically developing
      gender and age matched (+/- 3 months) peers were recruited from local schools.
      The PedsQLTM child self-report and proxy-report were individually or interviewer
      administered to the control group as required, and then compared to the group
      with specific language impairment. RESULTS: The PedsQLTM was reliable and
      feasible for use with the control group (N = 43, males = 35, age range = 5-16
      years, mean age = 8.74+/- 2.94 years). Control group performance was as expected
      as per the manual. Parents of the control group scored their children
      significantly higher than did the children themselves on all scales except the
      emotional functioning scale. Both the control group children and their parents
      scored themselves significantly higher on all scales, compared to children with
      severe specific language impairment and their parents. CONCLUSIONS: The PedsQLTM
      was suitable for use with the control group. Further, the recruitment of a
      control group provided additional clarity on the extent a severe specific
      language impairment impacts on an Australian child's perceived health-related
      quality of life, compared to the manual cut-off scores. Severe specific language
      impairment significantly impacts negatively on the health-related quality of life
      of Australian children across all domains, particularly when compared to an age
      and gender-matched group of peers. These results warrant the inclusion of health
      related quality of life evaluations in the assessment of these children along
      with a multidisciplinary approach.

PMID- 29444655
TI  - A systematic study on the prevention and treatment of retinopathy of prematurity
      in China.
AB  - BACKGROUND: To identify the prevention situation, the main factors influencing
      prevention effects and to develop control measures over retinopathy of
      prematurity in China. METHODS: Using stratified random sampling method, we
      randomly selected 23 provincial and ministerial hospitals (8 in Guangdong
      province, 5 in Hunan province and 10 in Shaanxi province), 81 municipal hospitals
      (38 in Guangdong province, 19 in Hunan province and 24 in Shaanxi province), 180
      district and county hospitals (76 in Guangdong province, 57 in Hunan province and
      47 in Shaanxi province) in China. A total of 284 hospitals were enrolled in the
      study, with questionnaires distributed investigating the status and constrain
      factors of ROP presentation. Significant outcomes were analyzed thereafter by
      SPSS 19.0. RESULTS: The screening rate of ROP in medical institutions from
      eastern, central and western China were 84.6%, 35.0% and 56.7%, respectively. The
      screening rate of tertiary and secondary medical institutions were 84.6% and
      25.7% in the eastern, 35.0% and 4.9% in the central, 56.7% and 5.9% in the
      western region. Screening was carried out better in the tertiary than that in the
      secondary and primary institutions. Treatment for ROP was available in 15.7% of
      all the tertiary hospitals surveyed. Lack of professionals, equipments and
      technologies were considered to be major restrain factors for screening.
      CONCLUSIONS: The ROP screening and treatment status have demonstrated significant
      regional diversity due to uneven distribution of medical resources in China.
      Developed areas had established intraregional cooperation models, whereas less
      developed areas should consider set up a large-scale, three-level ROP prevention
      network. It is of paramount importance that education and training towards
      ophthalmologists should be vigorously strengthened. It is strongly recommended
      that implement ROP telemedicine and integrated ROP prevention and management
      platforms through the Internet should be established.

PMID- 29444656
TI  - Implementation of a successful eradication protocol for Burkholderia Cepacia
      complex in cystic fibrosis patients.
AB  - BACKGROUND: Infection with Burkholderia cepacia complex (Bcc) results in a
      heterogeneous clinical course ranging from asymptomatic colonization of the
      airways to fulminant respiratory failure in patients with cystic fibrosis (CF).
      Early eradication of Pseudomonas aeruginosa improves clinical outcomes. The
      efficacy and clinical outcomes following implementation of an eradication
      protocol for Bcc are less well understood. METHODS: We developed and implemented
      a single center Bcc eradication protocol that included an intensive combination
      of intravenous, inhaled, and oral antibiotic therapies based on in vitro
      sensitivities. We conducted a retrospective cohort analysis of clinical outcomes
      compared to patients with chronic Bcc infection. RESULTS: Six patients were
      identified as having a newly acquired Bcc colonization and were placed on the
      eradication protocol. Sequential sputum samples after completion of the protocol
      demonstrated sustained clearance of Bcc in all patients. Lung function and
      nutritional status remained stable in the year following eradication. CONCLUSION:
      Clearance of Bcc from sputum cultures using a standardized protocol was
      successful at one year and was associated with clinical stability.

PMID- 29444657
TI  - Understanding the rapid increase in life expectancy in shanghai, China: a
      population-based retrospective analysis.
AB  - BACKGROUND: Life expectancy at birth (LE) is a comprehensive measure that
      accounts for age-specific death rates in a population. Shanghai has ranked first
      in LE in China mainland for decades. Understanding the reasons behind its
      sustained gain in LE provides a good reflection of many other cities in China.
      The aim of this study is intended to explore temporal trend in age- and cause
      specific gains in LE in Shanghai and the probable reasons lay behind. METHODS:
      Joinpoint regression was applied to evaluate temporal trend in LE and the long
      time span was then divided accordingly. Contributions to change in LE (1973-2015)
      were decomposed by age and cause at corresponding periods. RESULTS: LE in
      Shanghai could be divided into four phases ie., descent (1973-1976), recovery
      (1976-1998), rapid rise (1998-2004) and slow rise (2004-2015). The growing LE was
      mainly attributed to reductions in mortality from the elderly populations and
      chronic diseases such as cerebrovascular disease, chronic lower respiratory
      disease, and gastrointestinal cancers (stomach, liver and esophageal cancer).
      CONCLUSIONS: The four-decade sustained gain in LE in Shanghai is due to the
      reductions in mortality from the elderly and chronic diseases such as
      cerebrovascular disease, chronic lower respiratory disease, and gastrointestinal
      cancers. Further growth momentum still comes from the elderly population.

PMID- 29444658
TI  - Impact of tobacco control policies on adolescent smokeless tobacco and cigar use:
      a difference-in-differences approach.
AB  - BACKGROUND: While increasing cigarette taxes has been a major policy driver to
      decrease smoking, taxes on other tobacco products have received less attention.
      Our aims were to evaluate the impact of chewing tobacco/cigar taxes, cigarette
      taxes, and smoke-free legislation on adolescent male and female use of smokeless
      tobacco and cigars. METHODS: We analyzed data on 499,381 adolescents age 14-18
      years from 36 US states in the Youth Risk Behavior Surveys (1999-2013) linked to
      state-level tobacco control policies. We conducted difference-in-differences
      regression models to assess whether changes in taxes and the enactment of smoke
      free legislation were associated with smokeless tobacco use and, separately,
      cigar use. Models were stratified by adolescent sex. RESULTS: We found that
      chewing tobacco taxes had no effect on smokeless tobacco use and cigar taxes had
      no effect on cigar use. In contrast, among males a 10% increase in cigarette
      taxes was associated with a 1.0 percentage point increase (0.0010, 95% CI 0.0003
      0.0017) in smokeless tobacco use. A 10% increase in cigarette taxes was also
      associated with a 1.5 percentage point increase (0.0015, 95% CI 0.0006-0.0024) in
      cigar use among males and a 0.7 percentage point increase (0.0007, 95% CI 0.0001
      0.0013) in cigar use among females. There was some evidence that smoke-free
      legislation was associated with an 1.1 percentage point increase (0.0105, 95% CI
      0.0015-0.0194) in smokeless tobacco use among males only, but no effect of smoke
      free legislation on cigar use for males or females. CONCLUSIONS: Higher state
      cigarette taxes are associated with adolescents' use of cheaper, alternative
      tobacco products such as smokeless tobacco and cigars. Reducing tobacco use will
      require comprehensive tobacco control policies that are applied equally to and
      inclusive of all tobacco products.

PMID- 29444659
TI  - Right-to-left shunt and subclinical ischemic brain lesions in Chinese
      migraineurs: a multicentre MRI study.
AB  - BACKGROUND: Migraine is considered as a risk factor for subclinical brain
      ischemic lesions, and right-to-left shunt (RLS) is more common among migraineurs.
      This cross-sectional study assessed the association of RLS with the increased
      prevalence of subclinical ischemic brain lesions in migraineurs. METHODS: We
      enrolled 334 migraineurs from a multicentre study from June 2015 to August 2016.
      Participants were all evaluated using contrast-enhanced transcranial Doppler,
      magnetic resonance imaging (MRI), and completed a questionnaire covering
      demographics, the main risk factors of vascular disease, and migraine status. RLS
      was classified into four grades (Grade 0 = Negative; Grade I = 1 <= microbubbles
      (MBs) <= 10; Grade II = MBs > 10 and no curtain; Grade III = curtain). Silent
      brain ischemic infarctions (SBI) and white matter hyperintensities (WMHs) were
      evaluated on MRI. RESULTS: We found no significant differences between
      migraineurs with RLS and migraineurs without RLS in subclinical ischemic brain
      lesions.SBI and WMHs did not increase with the size of the RLS(p for trend for
      SBI = 0.066, p for trend for WMHs = 0.543). Furthermore, curtain RLS in
      migraineurs was a risk factor for the presence of SBI (p = 0.032, OR = 3.47;
      95%CI: 1.12-10.76). There was no association between RLS and the presence of
      WMHs. CONCLUSION: Overall, RLS is not associated with increased SBI or WMHs in
      migraineurs. However, when RLS is present as a curtain pattern, it is likely to
      be a risk factor for SBIs in migraineurs. TRIAL REGISTRATION: No. NCT02425696 ;
      registered on April 21, 2015.

PMID- 29444661
TI  - RNA-QC-chain: comprehensive and fast quality control for RNA-Seq data.
AB  - BACKGROUND: RNA-Seq has become one of the most widely used applications based on
      next-generation sequencing technology. However, raw RNA-Seq data may have quality
      issues, which can significantly distort analytical results and lead to erroneous
      conclusions. Therefore, the raw data must be subjected to vigorous quality
      control (QC) procedures before downstream analysis. Currently, an accurate and
      complete QC of RNA-Seq data requires of a suite of different QC tools used
      consecutively, which is inefficient in terms of usability, running time, file
      usage, and interpretability of the results. RESULTS: We developed a
      comprehensive, fast and easy-to-use QC pipeline for RNA-Seq data, RNA-QC-Chain,
      which involves three steps: (1) sequencing-quality assessment and trimming; (2)
      internal (ribosomal RNAs) and external (reads from foreign species) contamination
      filtering; (3) alignment statistics reporting (such as read number, alignment
      coverage, sequencing depth and pair-end read mapping information). This package
      was developed based on our previously reported tool for general QC of next
      generation sequencing (NGS) data called QC-Chain, with extensions specifically
      designed for RNA-Seq data. It has several features that are not available yet in
      other QC tools for RNA-Seq data, such as RNA sequence trimming, automatic rRNA
      detection and automatic contaminating species identification. The three QC steps
      can run either sequentially or independently, enabling RNA-QC-Chain as a
      comprehensive package with high flexibility and usability. Moreover, parallel
      computing and optimizations are embedded in most of the QC procedures, providing
      a superior efficiency. The performance of RNA-QC-Chain has been evaluated with
      different types of datasets, including an in-house sequencing data, a semi
      simulated data, and two real datasets downloaded from public database.
      Comparisons of RNA-QC-Chain with other QC tools have manifested its superiorities
      in both function versatility and processing speed. CONCLUSIONS: We present here a
      tool, RNA-QC-Chain, which can be used to comprehensively resolve the quality
      control processes of RNA-Seq data effectively and efficiently.

PMID- 29444660
TI  - Volunteers in Ethiopia's women's development army are more deprived and
      distressed than their neighbors: cross-sectional survey data from rural Ethiopia.
AB  - BACKGROUND: Many Community Health Workers (CHWs) experience the same
      socioeconomic and health needs as their neighbors, given that they are by
      definition part of their communities. Yet very few studies aim to measure and
      characterize experiences of deprivation, poverty, and wellbeing among community
      health workers. This study quantitatively examines deprivation and wellbeing in
      Ethiopia's Women's Development Army (WDA), a massive unpaid community health
      workforce intended to improve population health and modernize the country.
      METHODS: We conducted a survey of 422 volunteer WDA leaders and community members
      in rural Amhara state, part of a mixed-methods ethnographic study of the
      experiences of women in the WDA. The survey asked a variety of questions about
      respondents' demographics, education, assets, and access to government services.
      We also used survey measures to evaluate respondents' levels of household food
      and water security, stressful life events, social support, work burden, and
      psychological distress. RESULTS: Volunteer WDA leaders and community members
      alike tend to have very low levels of schooling and household assets, and to be
      heavily burdened with daily work in several domains. Large proportions are food
      and water insecure, many are in debt, and many experience stretches of time with
      no money at all. Our survey also revealed differences between volunteer WDA
      leaders and other women that warrant attention. Leaders are less likely to be
      married and more likely to be divorced or separated. Leaders are also more likely
      to experience some aspects of food insecurity and report greater levels of
      psychological distress and more stressful life events. They also report slightly
      less social support than other women. CONCLUSIONS: In rural Amhara, women who
      seek out and/or are sought and recruited for leader roles in the WDA are a
      population living in precarity. In several domains, they experience even more
      hardship than their neighbors. These findings highlight a need for careful
      attention and further research into processes of volunteer CHW selection, and to
      determine whether or not volunteering for CHW programs increases socioeconomic
      and health risks among volunteers. CHW programs in settings of poverty should
      stop using unpaid labor and seek to create more paid CHW jobs.

PMID- 29444663
TI  - Gender-related differences in cardiometabolic risk factors and lifestyle
      behaviors in treatment-seeking adolescents with severe obesity.
AB  - BACKGROUND: Obesity during adolescence is associated with cardiovascular
      mortality in adulthood. The adverse obesity-related cardiometabolic risk profile
      is already observed in adolescence. We aimed to examine possible gender
      differences in cardiometabolic risk factors and lifestyle behaviors among
      adolescents with severe obesity, hypothesizing that boys would have both a higher
      prevalence of the metabolic syndrome as well as less healthy lifestyle behaviors
      than girls. METHODS: Cross-sectional study of treatment-seeking adolescents with
      severe obesity who attended the Morbid Obesity Centre at Vestfold Hospital Trust
      and who were consecutively enrolled in the Vestfold Register of Obese Children
      between September 2009 and September 2015. A total of 313 adolescents aged 12 to
      18 years were recruited, whereof 268 subjects (49% boys) completed a food and
      activity frequency questionnaire and were included in the analysis. RESULTS: Mean
      (SD) age, BMI and BMI SDS were 15 (1.6) years, 38.6 (5.9) kg/m2 and 3.5 (0.6).
      Levels of LDL cholesterol, fasting insulin and glucose and diastolic blood
      pressure (DBP) did not differ between genders. Compared to girls, boys had
      significantly higher triglycerides (p = 0.037) and systolic blood pressure (SBP)
      (p = 0.003), as well as lower HDL cholesterol (p = 0.002). The metabolic syndrome
      was present in 27% of the boys and 19% of the girls (p = 0.140), and the
      prevalence of high DBP, dyslipidemia and dysglycemia also did not differ
      significantly between genders. The prevalence of high SBP was higher in boys than
      in girls (19% vs. 9%, p = 0.021). Gender was associated with a number of
      lifestyle habits, as a larger proportions of boys had higher screen time (p =
      0.032), more regular breakfast eating (p = 0.023), higher intake of sugar
      sweetened soda (p = 0.036), and lower intake of vegetables than girls (p =
      0.011). By contrast, physical activity level and intake of fruit and berries did
      not differ between genders. CONCLUSIONS: Male treatment-seeking adolescents with
      severe obesity had a more unfavorable set of metabolic and behavioral risk
      factors for cardiovascular disease than girls. Our results indicate that
      lifestyle behavioral markers should be thoroughly assessed in both genders, and
      possible gender-related differences in risk profile should be taken into account
      in future treatment programs.

PMID- 29444662
TI  - A systematic approach to RNA-associated motif discovery.
AB  - BACKGROUND: Sequencing-based large screening of RNA-protein and RNA-RNA
      interactions has enabled the mechanistic study of post-transcriptional RNA
      processing and sorting, including exosome-mediated RNA secretion. The downstream
      analysis of RNA binding sites has encouraged the investigation of novel sequence
      motifs, which resulted in exceptional new challenges for identifying motifs from
      very short sequences (e.g., small non-coding RNAs or truncated messenger RNAs),
      where conventional methods tend to be ineffective. To address these challenges,
      we propose a novel motif-finding method and validate it on a wide range of RNA
      applications. RESULTS: We first perform motif analysis on microRNAs and longer
      RNA fragments from various cellular and exosomal sources, and then validate our
      prediction through literature search and experimental test. For example, a 4 bp
      long motif, GUUG, was detected to be responsible for microRNA loading in exosomes
      involved in human colon cancer (SW620). Additional performance comparisons in
      various case studies have shown that this new approach outperforms several
      existing state-of-the-art methods in detecting motifs with exceptional high
      coverage and explicitness. CONCLUSIONS: In this work, we have demonstrated the
      promising performance of a new motif discovery approach that is particularly
      effective in current RNA applications. Important discoveries resulting from this
      work include the identification of possible RNA-loading motifs in a variety of
      exosomes, as well as novel insights in sequence features of RNA cargos, i.e.,
      short non-coding RNAs and messenger RNAs may share similar loading mechanism into
      exosomes. This method has been implemented and deployed as a new webserver named
      MDS2 which is accessible at http://sbbi-panda.unl.edu/MDS2/ , along with a
      standalone package available for download at https://github.com/sbbi/MDS2 .

PMID- 29444665
TI  - Comparison of 1-year outcomes after Ahmed glaucoma valve implantation with and
      without Ologen adjuvant.
AB  - BACKGROUND: Many studies have investigated the clinical benefits of Ologen for
      trabeculectomy. However, its benefits for Ahmed glaucoma valve (AGV) implantation
      have not been investigated as extensively. The aim of this study was to compare
      the 1-year outcomes of AGV implantation with and without Ologen adjuvant for the
      treatment of refractory glaucoma. METHODS: This retrospective study included a
      total of 20 eyes of 20 glaucoma patients, who were followed for at least 1-year
      after undergoing AGV implantation. In 12 eyes of 12 patients, conventional AGV
      (CAGV) surgery was performed, while in 8 eyes of 8 patients, Ologen-augmented AGV
      (OAGV) implantation was performed. The outcomes were evaluated according to
      intraocular pressure (IOP) and the number of IOP-lowering medications. Complete
      success was defined as IOP <= 21 mmHg without medications throughout the 1-year
      follow-up period, and qualified success was defined as IOP <= 21 mmHg with or
      without medications throughout the 1-year follow-up period. RESULTS: The rate of
      complete success was significantly higher in the OAGV group (50.0%) than in the
      CAGV group (8.3%) (p = 0.035). There were no significant differences between the
      two groups in terms of qualified success or incidence of the early hypertensive
      phase. The IOP changes were similar between the groups within 1-year
      postoperatively, though the number of IOP-lowering medications was significantly
      lower in the OAGV group during the early hypertensive phase (p = 0.031, 0.031,
      and 0.025 at postoperative months 1, 2, and 3, respectively). When subjects were
      divided into groups according to the occurrence of the early hypertensive phase,
      the group with early hypertensive phase was more likely to use IOP-lowering
      medications at postoperative 6 months and 1 year (p = 0.002 and 0.005,
      respectively). CONCLUSIONS: OAGV surgery shows encouraging results for patients
      with refractory glaucoma, specifically with respect to the achievement of
      complete success and the reduction of the number of IOP-lowering medications
      during the early hypertensive phase. Furthermore, our results suggest that
      occurrence of the early hypertensive phase is predictive of which patients will
      require IOP-lowering medications at postoperative 6 months and 1 year.

PMID- 29444664
TI  - The knitting community-based trial for older women with osteoarthritis of the
      hands: design and rationale of a randomized controlled trial.
AB  - BACKGROUND: The prevalence of hand osteoarthritis (HOA) has been reported to be
      higher amongst women over 50 years old (66%) compared to men of the same age
      (34%). Although exercise therapy has been shown effective in reducing symptoms
      and disability associated with HOA, adherence to treatment programs remains low.
      The primary objective of this RCT is to examine the effectiveness of a 12-week
      knitting program for morning stiffness (primary outcome) and pain relief
      (secondary outcome) 2 h post-wakening in females (aged 50 to 85 years old) with
      mild to moderate hand osteoarthritis (HOA). METHODS/DESIGN: A single-blind, two
      arm randomized controlled trial (RCT) with a parallel group design will be used
      to reach this objective and compare results to a control group receiving an
      educational pamphlet on osteoarththritis (OA) designed by the Arthritis Society.
      The premise behind the knitting program is to use a meaningful occupation as the
      main component of an exercise program. The knitting program will include two
      components: 1) bi-weekly 20-min knitting sessions at a senior's club and 2) 20
      min home daily knitting sessions for the five remaining weekdays. Participants
      assigned to the control group will be encouraged to read the educational pamphlet
      and continue with usual routine. Pain, morning stiffness, hand function, self
      efficacy and quality of life will be measured at baseline, six weeks, 12 weeks
      (end of program) with standardized tools. We hypothesize that participants in the
      knitting program will have significant improvements in all clinical outcomes
      compared to the control group. A published case study as well as the preliminary
      results of a feasibility study as examined through a 6-week pre-post study (n = 5
      women with HOA) involving 20-min daily knitting morning sessions led to this
      proposed randomized controlled trial research protocol. This article describes
      the intervention, the empirical evidence to support it. DISCUSSION: This knitting
      RCT has the potential to enhance our understanding of the daily HOA symptoms
      control and exercise adherence, refine functional exercise recommendations in
      this prevalent disease, and reduce the burden of disability in older women. TRIAL
      REGISTRATION: (ACTRN12617000843358) registered on 7/06/2017.

PMID- 29444666
TI  - Analysis of Total Knee Arthroplasty revision causes.
AB  - BACKGROUND: The number of revision Total Knee Arthroplasty (TKA) is rising in
      many countries. The aim of this study was the prospective assessment of the
      underlying causes leading to revision TKA in a tertiary care hospital and the
      comparison of those reasons with previously published data. METHODS: In this
      study patients who had revision TKA between 2010 and 2015 were prospectively
      included. Revision causes were categorized using all available information from
      patients' records including preoperative diagnostics, intraoperative findings as
      well as the results of the periprosthetic tissue analysis. According to previous
      studies patients were divided into early (up to 2 years) and late revision (more
      than 2 years). Additional also re-revisions after already performed revision TKA
      were included. RESULTS: We assessed 312 patients who underwent 402 revision TKA,
      89.6% of them were referred to our center for revision surgery. In 289 patients
      (71.9%) this was the first revision surgery after primary TKA. Among the first
      revisions the majority was late revisions (73.7%). One hundred thirteen patients
      (28.1%) had already had one or more revision surgeries before. Overall, the most
      frequent reason for revision was infection (36.1%) followed by aseptic loosening
      (21.9%) and periprosthetic fracture (13.7%). CONCLUSIONS: In a specialized
      arthroplasty center periprosthetic joint infection (PJI) was the most common
      reason for revision and re-revision TKA. This is in contrast to population-based
      registry data and has consequences on costs as well as on success rates in such
      centers.

PMID- 29444667
TI  - In vitro antileishmanial and cytotoxicity activities of essential oils from
      Haplophyllum tuberculatum A. Juss leaves, stems and aerial parts.
AB  - BACKGROUND: Plants used for traditional medicine produce diverse and complex
      secondary metabolites exhibiting various medicinal properties. The medicinal
      plant Haplophyllum tuberculatum is used by native people against malaria and
      parasitic infections. METHODS: In this study and in order to contribute for the
      search of new natural drugs for leishmaniasis, the essential oils of H.
      tuberculatum leaves, stems and aerial parts (leaves+stems) collected in two
      different periods, 2013 and 2015, and their components by GC/FID and GC/MS
      analyses were investigated. Those collected in 2013 were also re-analyzed two
      years later. The extracted oils were screened in vitro for anti-leishmanial
      activity on Leishmania mexicana mexicana (L.m.m.) promastigotes and cytotoxicity
      on the Chinese Hamster Ovary (CHO) cell line. Limonene (1.5 - 8%), its isomers (R
      (+)-limonene and S-(-)-limonene), linalool and octanol were also tested.
      RESULTS: Results showed that the chemical composition varied according to the
      year of collection. Though major compounds remain almost the same, qualitative
      and quantitative variations in the composition of the EOs can be observed between
      the two years of collection, with some minor compounds identified only in one
      type of samples. Variation in the composition were also observed in the re
      analyzed volatile oils, showing stability concerns. The essential oils and R-(+)
      limonene showed moderate anti-leishmanial activity. Their IC50 range from 6.48 to
      50.28 MUg/ml. Cytotoxicity assays for theses volatile extracts, R- (+)-limonene
      and S- (-)-limonene on CHO cells showed relatively potent cytotoxicity with a
      selectivity index <10. Their CC50 range from 27.79 to 82.56 MUg/ml. CONCLUSIONS:
      The findings of the present study demonstrated that H. tuberculatum might not be
      considered as a natural source for production of new anti-leishmanial agents
      without further analyzing its eventual in vivo toxicity as well as that of major
      pure compounds.

PMID- 29444669
TI  - Effects of multilevel posterior ligament dissection after spinal instrumentation
      on adjacent segment biomechanics as a potential risk factor for proximal
      junctional kyphosis: a biomechanical study.
AB  - BACKGROUND: Spinous processes and posterior ligaments, such as inter- and
      supraspinous ligaments are often sacrificed either deliberately to harvest
      osseous material for final spondylodesis e.g. in deformity corrective surgery or
      accidentally after posterior spinal instrumentation. This biomechanical study
      evaluates the potential destabilizing effect of a progressive dissection of the
      posterior ligaments (PL) after instrumented spinal fusion as a potential risk
      factor for proximal junctional kyphosis (PJK). METHODS: Twelve calf lumbar spines
      were instrumented from L3 to L6 (L3 = upper instrumented vertebra, UIV) and
      randomly assigned to one of the two study groups (dissection vs. control group).
      The specimens in the dissection group underwent progressive PL dissection,
      followed by cyclic flexion motion (250 cycles, moment: + 2.5 to + 20.0 Nm) to
      simulate physical activity and range of motion (ROM) testing of each segment with
      pure moments of +/-15.0 Nm after each dissection step. The segmental ROM in
      flexion and extension was measured. The control group underwent the same loading
      and ROM testing protocol, but without PL dissection. RESULTS: In the treatment
      group, the normalized mean ROM at L2-L3 (direct adjacent segment of interest,
      UIV/UIV + 1, PJK-level) increased to 104.7%, 107.3%, and 119.4% after dissection
      of the PL L4-L6, L3-L6, and L2-L6, respectively. In the control group the mean
      ROM increased only to 103.2%, 106.7%, and 108.7%. The ROM difference at L2-L3
      with regard to the last dissection of the PL was statistically significant (P =
      0.017) and a PL dissection in the instrumented segments showed a positive trend
      towards an increased ROM at UIV/UIV + 1. CONCLUSIONS: A dissection of the PL at
      UIV/UIV + 1 leads to a significant increase in ROM at this level which can be
      considered to be a risk factor for PJK and should be definitely avoided during
      surgery. However, a dissection of the posterior ligaments within the instrumented
      segments while preserving the ligaments at UIV/UIV + 1 leads to a slight but not
      significant increase in ROM in the adjacent cranial segment UIV/UIV + 1 in the
      used experimental setup. Using this experimental setup we could not confirm our
      initial hypothesis that the posterior ligaments within a long posterior
      instrumentation should be preserved.

PMID- 29444670
TI  - Breast cancer in Ethiopia: evidence for geographic difference in the distribution
      of molecular subtypes in Africa.
AB  - BACKGROUND: Breast cancer is a heterogeneous disease with several morphological
      and molecular subtypes. Widely accepted molecular classification system uses
      assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal
      growth factor receptor 2 (HER2) and proliferation marker Ki67. Few studies have
      been conducted on the incidence and molecular types of breast cancer in Sub
      Saharan Africa. Previous studies mainly from Western and Central Africa, showed
      breast cancer to occur at younger ages and to present with aggressive features,
      such as high-grade, advanced stage and triple-negative phenotype (negative for
      ER, PR and HER2). Limited data from East Africa including Ethiopia however shows
      hormone receptor negative tumors to account for a lower proportion of all breast
      cancers than has been reported from elsewhere in Africa. METHODS: In this study
      from Tikur Anbessa Specialized Hospital, 114 breast cancer patients diagnosed
      between 2012 and 2015 were enrolled. ER, PR, Ki67 and HER2 receptor status were
      assessed using immunohistochemistry from tissue microarrays. FISH was used for
      assessment of gene amplification in all equivocal tumor samples and for
      confirmation in HER2-enriched cases. RESULTS: The distribution of molecular
      subtypes was: Luminal A: 40%; Luminal B: 26%; HER2-enriched: 10%; TNBC: 23%. ER
      were positive in 65% of all tumors and 43% the cases were positive for PR. There
      was statistically significant difference in median age at diagnosis between the
      molecular subtypes (P < 0.05). There was a bimodal distribution of molecular
      subtypes in different age ranges with Luminal B subtype being more common at
      younger ages (median = 36) and Luminal A subtype more prevalent at older ages
      (median = 42). There were no statistically significant differences in tumor
      grade, histology, and stage between the molecular subtypes of breast cancer.
      CONCLUSION: The present study detected Luminal A breast cancer to be the most
      common subtype and reveals a relatively low rate of hormone receptor negative and
      TNBC. Our findings and results from other East African studies suggest geographic
      variability in the distribution of the molecular subtypes of breast cancer in
      Africa and hence have important clinical and policy implications for breast
      cancer control and treatment in Ethiopia.

PMID- 29444668
TI  - Gigantol inhibits Wnt/beta-catenin signaling and exhibits anticancer activity in
      breast cancer cells.
AB  - BACKGROUND: Gigantol is a bibenzyl compound derived from several medicinal
      orchids. This biologically active compound has been shown to have promising
      therapeutic potential against cancer cells, but its mechanism of action remains
      unclear. METHODS: The inhibitory effect of gigantol on Wnt/beta-catenin signaling
      was evaluated with the SuperTOPFlash reporter system. The levels of
      phosphorylated low-density lipoprotein receptor related protein 6 (LRP6), total
      LRP6 and cytosolic beta-catenin were determined by Western blot analysis. The
      expression of Wnt target genes was analyzed using real-time PCR. Cell viability
      was measured with a MTT assay. The effect of gigantol on cell migration was
      examined using scratch wound-healing and transwell migration assays. RESULTS:
      Gigantol decreased the level of phosphorylated LRP6 and cytosolic beta-catenin in
      HEK293 cells. In breast cancer MDA-MB-231 and MDA-MB-468 cells, treatment with
      gigantol reduced the level of phosphorylated LRP6, total LRP6 and cytosolic beta
      catenin in a dose-dependent manner, resulting in a decrease in the expression of
      Wnt target genes Axin2 and Survivin. We further demonstrated that gigantol
      suppressed the viability and migratory capacity of breast cancer cells.
      CONCLUSION: Gigantol is a novel inhibitor of the Wnt/beta-catenin pathway. It
      inhibits Wnt/beta-catenin signaling through downregulation of phosphorylated LRP6
      and cytosolic beta-catenin in breast cancer cells.

PMID- 29444671
TI  - Tailoring an educational program on the AHRQ Patient Safety Indicators to meet
      stakeholder needs: lessons learned in the VA.
AB  - BACKGROUND: Given that patient safety measures are increasingly used for public
      reporting and pay-for performance, it is important for stakeholders to understand
      how to use these measures for improvement. The Agency for Healthcare Research and
      Quality (AHRQ) Patient Safety Indicators (PSIs) are one particularly visible set
      of measures that are now used primarily for public reporting and pay-for
      performance among both private sector and Veterans Health Administration (VA)
      hospitals. This trend generates a strong need for stakeholders to understand how
      to interpret and use the PSIs for quality improvement (QI). The goal of this
      study was to develop an educational program and tailor it to stakeholders' needs.
      In this paper, we share what we learned from this program development process.
      METHODS: Our study population included key VA stakeholders involved in reviewing
      performance reports and prioritizing and initiating quality/safety initiatives. A
      pre-program formative evaluation through telephone interviews and web-based
      surveys assessed stakeholders' educational needs/interests. Findings from the
      formative evaluation led to development and implementation of a cyberseminar
      based program, which we tailored to stakeholders' needs/interests. A post-program
      survey evaluated program participants' perceptions about the PSI educational
      program. RESULTS: Interview data confirmed that the concepts we had developed for
      the interviews could be used for the survey. Survey results informed us on what
      program delivery mode and content topics were of high interest. Six cyberseminars
      were developed-three of which focused on two content areas that were noted of
      greatest interest: learning how to use PSIs for monitoring trends and
      understanding how to interpret PSIs. We also used snapshots of VA PSI reports so
      that participants could directly apply learnings. Although initial interest in
      the program was high, actual attendance was low. However, post-program survey
      results indicated that perceptions about the program were positive. CONCLUSIONS:
      Conducting a formative evaluation was a highly important process in program
      development. The useful information that we collected through the interviews and
      surveys allowed us to tailor the program to stakeholders' needs and interests.
      Our experiences, particularly with the formative evaluation process, yielded
      valuable lessons that can guide others when developing and implementing similar
      educational programs.

PMID- 29444672
TI  - Adherence to Mediterranean and low-fat diets among heart and lung transplant
      recipients: a randomized feasibility study.
AB  - BACKGROUND: Heart and lung transplant recipients are at a substantially increased
      risk of cardiovascular disease (CVD). Since both low-fat and Mediterranean diets
      can reduce CVD in immunocompetent people at high risk, we assessed adherence
      among thoracic transplant recipients allocated to one or other of these diets for
      12 months. METHODS: Forty-one transplant recipients (20 heart; 21 lung)
      randomized to a Mediterranean or a low-fat diet for 12 months received diet
      specific education at baseline. Adherence was primarily assessed by
      questionnaire: 14-point Mediterranean diet (score 0-14) and 9-point low-fat diet
      (score 0-16) respectively, high scores indicating greater adherence. Median
      scores at baseline, 6 months, 12 months, and 6-weeks post-intervention were
      compared by dietary group. We further assessed changes in weight, body mass index
      (BMI) and serum triglycerides from baseline to 12 months as an additional
      indicator of adherence. RESULTS: In those randomized to a Mediterranean diet,
      median scores increased from 4 (range 1-9) at baseline, to 10 (range 6-14) at 6
      months and were maintained at 12 months, and also at 6-weeks post-intervention
      (median 10, range 6-14). Body weight, BMI and serum triglycerides decreased over
      the 12-month intervention period (mean weight - 1.8 kg, BMI -0.5 kg/m2,
      triglycerides - 0.17 mmol/L). In the low-fat diet group, median scores were 11
      (range 9-14) at baseline; slightly increased to 12 (range 9-16) at 6 months, and
      maintained at 12 months and 6 weeks post-intervention (median 12, range 8-15).
      Mean changes in weight, BMI and triglycerides were - 0.2 kg, 0.0 kg/m2 and - 0.44
      mmol/L, respectively. CONCLUSIONS: Thoracic transplant recipients adhered to
      Mediterranean and low-fat dietary interventions. The change from baseline eating
      habits was notable at 6 months; and this change was maintained at 12 months and 6
      weeks post-intervention in both Mediterranean diet and low-fat diet groups.
      Dietary interventions based on comprehensive, well-supported education sessions
      targeted to both patients and their family members are crucial to success. Such
      nutritional strategies can help in the management of their substantial CVD risk.
      TRIAL REGISTRATION: The IRAS trial registry ( ISRCTN63500150 ). Date of
      registration 27 July 2016. Retrospectively registered.

PMID- 29444673
TI  - Effect of tt-farnesol and myricetin on in vitro biofilm formed by Streptococcus
      mutans and Candida albicans.
AB  - BACKGROUND: Dental caries is considered a multifactorial disease, in which
      microorganisms play an important role. The diet is decisive in the biofilm
      formation because it provides the necessary resources for cellular growth and
      exopolysaccharides synthesis. Exopolysaccharides are the main components of the
      extracellular matrix (ECM). The ECM provides a 3D structure, support for the
      microorganisms and form diffusion-limited environments (acidic niches) that cause
      demineralization of the dental enamel. Streptococcus mutans is the main producer
      of exopolysaccharides. Candida albicans is detected together with S. mutans in
      biofilms associated with severe caries lesions. Thus, this study aimed to
      determine the effect of tt-farnesol and myricetin topical treatments on
      cariogenic biofilms formed by Streptococcus mutans and Candida albicans. METHODS:
      In vitro dual-species biofilms were grown on saliva-coated hydroxyapatite discs,
      using tryptone-yeast extract broth with 1% sucrose (37  degrees C, 5% CO2). Twice
      daily topical treatments were performed with: vehicle (ethanol 15%, negative
      control), 2 mM myricetin, 4 mM tt-farnesol, myricetin + tt-farnesol, myricetin +
      tt-farnesol + fluoride (250 ppm), fluoride, and chlorhexidine digluconate (0.12%;
      positive control). After 67 h, biofilms were evaluated to determine biofilm
      biomass, microbial population, and water-soluble and -insoluble
      exopolysaccharides in the ECM. RESULTS: Only the positive control yielded a
      reduced quantity of biomass and microbial population, while tt-farnesol treatment
      was the least efficient in reducing C. albicans population. The combination
      therapy myricetin + farnesol + fluoride significantly reduced water-soluble
      exopolysaccharides in the ECM (vs. negative control; p < 0.05; ANOVA one-way,
      followed by Tukey's test), similarly to the positive control. CONCLUSIONS:
      Therefore, the combination therapy negatively influenced an important virulence
      trait of cariogenic biofilms. However, the concentrations of both myricetin and
      tt-farnesol should be increased to produce a more pronounced effect to control
      these biofilms.

PMID- 29444674
TI  - The gendered experience with respect to health-seeking behaviour in an urban slum
      of Kolkata, India.
AB  - BACKGROUND: Empirical evidence shows that the relationship between health-seeking
      behaviour and diverse gender elements, such as gendered social status, social
      control, ideology, gender process, marital status and procreative status, changes
      across settings. Given the high relevance of social settings, this paper intends
      to explore how gender elements interact with health-seeking practices among men
      and women residing in an Indian urban slum, in consideration of the unique socio
      cultural context that characterises India's slums. METHODS: The study was
      conducted in Sahid Smriti Colony, a peri-urban slum of Kolkata, India. The
      referral technique was used for selecting participants, as people in the study
      area were not very comfortable in discussing their health issues and health
      seeking behaviours. The final sample included 66 participants, 34 men and 32
      women. Data was collected through individual face-to-face in-depth interviews
      with a semi-structured questionnaire. RESULTS: The data analysis shows six
      categories of reasons underlying women's preferences for informal healers, which
      are presented in the form of the following themes: cultural competency of care,
      easy communication, gender-induced affordability, avoidance of social stigma and
      labelling, living with the burden of cultural expectations and geographical and
      cognitive distance of formal health care. In case of men ease of access, quality
      of treatment and expected outcome of therapies are the three themes that emerged
      as the reasons behind their preferences for formal care. CONCLUSION: Our results
      suggest that both men and women utilise formal and informal care, but with
      different motives and expectations, leading to contrasting health-seeking
      outcomes. These gender-induced contrasts relate to a preference for socio
      cultural (women) versus technological (men) therapies and long (women) versus
      fast (men) treatment, and are linked to their different societal and familial
      roles. The role of women in following and maintaining socio-cultural norms leads
      them to focus on care that involves long discussions mixed with socio-cultural
      traits that help avoid economic and social sanctions, while the role of men as
      bread earners requires them to look for care that ensures a fast and complete
      recovery so as to avoid financial pressures.

PMID- 29444675
TI  - Current and future distribution of Aedes aegypti and Aedes albopictus (Diptera:
      Culicidae) in WHO Eastern Mediterranean Region.
AB  - BACKGROUND: Aedes-borne diseases as dengue, zika, chikungunya and yellow fever
      are an emerging problem worldwide, being transmitted by Aedes aegypti and Aedes
      albopictus. Lack of up to date information about the distribution of Aedes
      species hampers surveillance and control. Global databases have been compiled but
      these did not capture data in the WHO Eastern Mediterranean Region (EMR), and any
      models built using these datasets fail to identify highly suitable areas where
      one or both species may occur. The first objective of this study was therefore to
      update the existing Ae. aegypti (Linnaeus, 1762) and Ae. albopictus (Skuse, 1895)
      compendia and the second objective was to generate species distribution models
      targeted to the EMR. A final objective was to engage the WHO points of contacts
      within the region to provide feedback and hence validate all model outputs.
      METHODS: The Ae. aegypti and Ae. albopictus compendia provided by Kraemer et al.
      (Sci Data 2:150035, 2015; Dryad Digit Repos, 2015) were used as starting points.
      These datasets were extended with more recent species and disease data. In the
      next step, these sets were filtered using the Koppen-Geiger classification and
      the Mahalanobis distance. The occurrence data were supplemented with pseudo
      absence data as input to Random Forests. The resulting suitability and maximum
      risk of establishment maps were combined into hard-classified maps per country
      for expert validation. RESULTS: The EMR datasets consisted of 1995 presence
      locations for Ae. aegypti and 2868 presence locations for Ae. albopictus. The
      resulting suitability maps indicated that there exist areas with high suitability
      and/or maximum risk of establishment for these disease vectors in contrast with
      previous model output. Precipitation and host availability, expressed as
      population density and night-time lights, were the most important variables for
      Ae. aegypti. Host availability was the most important predictor in case of Ae.
      albopictus. Internal validation was assessed geographically. External validation
      showed high agreement between the predicted maps and the experts' extensive
      knowledge of the terrain. CONCLUSION: Maps of distribution and maximum risk of
      establishment were created for Ae. aegypti and Ae. albopictus for the WHO EMR.
      These region-specific maps highlighted data gaps and these gaps will be filled
      using targeted monitoring and surveillance. This will increase the awareness and
      preparedness of the different countries for Aedes borne diseases.

PMID- 29444676
TI  - Parameters influencing hand grip strength measured with the manugraphy system.
AB  - BACKGROUND: This study aimed to determine whether sex, hand length and the
      individual training status affect hand strength and whether these measurements
      differ if they are recorded using the Jamar dynamometer or a new cylindrical
      measuring system. METHODS: For this purpose, 152 healthy adults were examined
      using a new manugraphy measuring system (novel, Munich, Germany) comprising two
      measuring cylinders of different sizes and a Jamar electronic dynamometer with
      two grip positions corresponding approximately to the sizes of the cylinders. A
      descriptive analysis was performed as well as a correlation analysis using the
      Pearson correlation coefficient. To prepare predictive models, multiple linear
      regression analyses were carried out to determine factors that influence the
      force and p <= 0.05 was considered statistically significant. RESULTS: A
      significant difference in the maximum and mean strength was observed that is
      dependent on sex, with men stronger than women, in line with expectations, and
      hand length, with small hands able to exert less force than large hands. No
      consistent increase in strength could be attributed to repetitive manual loads
      applied either at work or in leisure activities. CONCLUSIONS: Both measurement
      techniques yielded similar results, suggesting that manugraphy is well suited for
      clinical research purposes because it not only takes measurements that are just
      as reproducible and valid as the conventional measurement technique but in doing
      so measures not just the total strength of a hand but also enables more precise
      comparisons of isolated hand regions applying dynamic measurements.

PMID- 29444677
TI  - Neuroprotective effects of seaweeds against 6-hydroxidopamine-induced cell death
      on an in vitro human neuroblastoma model.
AB  - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder
      of the central nervous system. Although the causes of PD pathogenesis remain
      incomplete, some evidences has suggested that oxidative stress is an important
      mediator in its pathogenesis. The aim of this study was to evaluate the
      protective effects of seaweeds with high antioxidant activity on 6
      hydroxydopamine (6-OHDA)-induced neurotoxicity in the human neuroblastoma cell
      line SH-SY5Y, as well as the associated intracellular signaling pathways.
      METHODS: Cell viability studies were assessed by 3-(4,5-dimethylthiazol-2yl)-2,5
      diphenyltetrazolium (MTT) bromide assay and the intracellular signaling pathways
      analyzed were: hydrogen peroxide (H2O2) production, changes in the mitochondrial
      membrane potential and Caspase-3 activity. RESULTS: Exposure of SH-SY5Y cells to
      6-OHDA (10-1000 MUM) reduced cell's viability in a concentration and time
      dependent manner. The data suggest that the cell death induced by 6-OHDA was
      mediated by an increase of H2O2 production, the depolarization of mitochondrial
      membrane potential and the increase of Caspase-3 activity. Extracts from S.
      polyshides, P. pavonica, S. muticum, C. tomentosum and U. compressa revealed to
      efficiently protect cell's viability in the presence of 6-OHDA (100 MUM; 24 h).
      These effects appear to be associated with the reduction of H2O2 cell's
      production, the protection of mitochondrial membrane's potential and the
      reduction of Caspase-3 activity. CONCLUSIONS: These results suggest that seaweeds
      can be a promising source of new compounds with neuroprotective potential.

PMID- 29444678
TI  - The wild taxa utilized as vegetables in Sicily (Italy): a traditional component
      of the Mediterranean diet.
AB  - BACKGROUND: Wild vegetables in the Mediterranean Basin are still often consumed
      as a part of the diet and, in particular, there is a great tradition regarding
      their use in Sicily. In this study, an ethnobotanical field investigation was
      carried out to (a) identify the wild native taxa traditionally gathered and
      consumed as vegetables in Sicily, comparing the collected ethnobotanical data
      with those of other countries that have nominated the Mediterranean diet for
      inclusion in the UNESCO Representative List of the Intangible Cultural Heritage
      of Humanity and (b) highlight new culinary uses of these plants. METHODS:
      Interviews were carried out in 187 towns and villages in Sicily between 2005 and
      2015. A total of 980 people over the age of 50 were interviewed (mainly farmers,
      shepherds, and experts on local traditions). Plants recorded were usually
      collected in collaboration with the informants to confirm the correct
      identification of the plants. The frequencies of citation were calculated.
      RESULTS: Two hundred fifty-three taxa (specific and intraspecific) belonging to
      39 families, and 128 genera were recorded (26 were cited for the first time). The
      most represented families were Asteraceae, Brassicaceae, Apiaceae,
      Amaryllidaceae, Malvaceae, and Polygonaceae. Only 14 taxa were cited by 75% of
      the people interviewed. The aerial parts of wild plants, including leaves, tender
      shoots, and basal rosettes, are the main portions collected, while the
      subterranean parts are used to a lesser extent. For some vegetables, more parts
      are utilized. Most of the reported vegetables are consumed cooked. In addition to
      the widely known vegetables (Borago officinalis, Beta spp., Cichorium spp.,
      Brassica spp., Carduus spp., etc.), the so-called ancient vegetables are included
      (Onopordum illyricum, Centaurea calcitrapa, Nasturtium officinale, Scolymus spp.,
      Smyrnium rotundifolium), and some unique uses were described. Comparing the
      Sicilian findings to those from other countries, a very high number of vegetable
      taxa were detected, 72 of which are eaten only in Sicily, while 12 are consumed
      in all the Mediterranean countries examined. CONCLUSIONS: The research shows a
      high level of Sicilian knowledge about using wild plants as a traditional food
      source. Wild vegetables are healthy and authentic ingredients for local and
      ancient recipes, which are fundamental to the revitalization of quality food
      strictly connected to traditional agroecosystems.

PMID- 29444679
TI  - Understanding perceived availability and importance of tobacco control
      interventions to inform European adoption of a UK economic model: a cross
      sectional study.
AB  - BACKGROUND: The evidence on the extent to which stakeholders in different
      European countries agree with availability and importance of tobacco-control
      interventions is limited. This study assessed and compared stakeholders' views
      from five European countries and compared the perceived ranking of interventions
      with evidence-based ranking using cost-effectiveness data. METHODS: An interview
      survey (face-to-face, by phone or Skype) was conducted between April and July
      2014 with five categories of stakeholders - decision makers, service purchasers,
      service providers, evidence generators and health promotion advocates - from
      Germany, Hungary, the Netherlands, Spain, and the United Kingdom. A list of
      potential stakeholders drawn from the research team's contacts and snowballing
      served as the sampling frame. An email invitation was sent to all stakeholders in
      this list and recruitment was based on positive replies. Respondents were asked
      to rate availability and importance of 30 tobacco control interventions. Kappa
      coefficients assessed agreement of stakeholders' views. A mean importance score
      for each intervention was used to rank the interventions. This ranking was
      compared with the ranking based on cost-effectiveness data from a published
      review. RESULTS: Ninety-three stakeholders (55.7% response rate) completed the
      survey: 18.3% were from Germany, 17.2% from Hungary, 30.1% from the Netherlands,
      19.4% from Spain, and 15.1% from the UK. Of those, 31.2% were decision makers,
      26.9% evidence generators, 19.4% service providers, 15.1% health-promotion
      advocates, and 7.5% purchasers of services/pharmaceutical products. Smoking
      restrictions in public areas were rated as the most important intervention (mean
      score = 1.89). The agreement on availability of interventions between the
      stakeholders was very low (kappa = 0.098; 95% CI = [0.085, 0.111] but the
      agreement on the importance of the interventions was fair (kappa = 0.239; 95% CI
      = [0.208, 0.253]). A correlation was found between availability and importance
      rankings for stage-based interventions. The importance ranking was not
      statistically concordant with the ranking based on published cost-effectiveness
      data (Kendall rank correlation coefficient = 0.40; p-value = 0.11; 95% CI = [-
      0.09, 0.89]). CONCLUSIONS: The intrinsic differences in stakeholder views must be
      addressed while transferring economic evidence Europe-wide. Strong engagement
      with stakeholders, focussing on better communication, has a potential to mitigate
      this challenge.

PMID- 29444680
TI  - Experiences from ten years of incident reporting in health care: a qualitative
      study among department managers and coordinators.
AB  - BACKGROUND: Incident reporting (IR) in health care has been advocated as a means
      to improve patient safety. The purpose of IR is to identify safety hazards and
      develop interventions to mitigate these hazards in order to reduce harm in health
      care. Using qualitative methods is a way to reveal how IR is used and perceived
      in health care practice. The aim of the present study was to explore the
      experiences of IR from two different perspectives, including heads of departments
      and IR coordinators, to better understand how they value the practice and their
      thoughts regarding future application. METHODS: Data collection was performed in
      Ostergotland County, Sweden, where an electronic IR system was implemented in
      2004, and the authorities explicitly have advocated IR from that date. A
      purposive sample of nine heads of departments from three hospitals were
      interviewed, and two focus group discussions with IR coordinators took place.
      Data were analysed using qualitative content analysis. RESULTS: Two main themes
      emerged from the data: "Incident reporting has come to stay" building on the
      categories entitled perceived advantages, observed changes and value of the IR
      system, and "Remaining challenges in incident reporting" including the categories
      entitled need for action, encouraged learning, continuous culture improvement, IR
      system development and proper use of IR. CONCLUSIONS: After 10 years, the
      practice of IR is widely accepted in the selected setting. IR has helped to put
      patient safety on the agenda, and a cultural change towards no blame has been
      observed. The informants suggest an increased focus on action, and further
      development of the tools for reporting and handling incidents.

PMID- 29444681
TI  - Fermentative hydrogen production using pretreated microalgal biomass as
      feedstock.
AB  - Microalgae are simple chlorophyll containing organisms, they have high
      photosynthetic efficiency and can synthesize and accumulate large quantities of
      carbohydrate biomass. They can be cultivated in fresh water, seawater and
      wastewater. They have been used as feedstock for producing biodiesel, bioethanol
      and biogas. The production of these biofuels can be integrated with CO2
      mitigation, wastewater treatment, and the production of high-value chemicals.
      Biohydrogen from microalgae is renewable. Microalgae have several advantages
      compared to terrestrial plants, such as higher growth rate with superior CO2
      fixation capacity; they do not need arable land to grow; they do not contain
      lignin. In this review, the biology of microalgae and the chemical composition of
      microalgae were briefly introduced, the advantages and disadvantages of hydrogen
      production from microalgae were discussed, and the pretreatment of microalgal
      biomass and the fermentative hydrogen production from microalgal biomass
      pretreated by different methods (including physical, chemical, biological and
      combined methods) were summarized and evaluated. For the production of
      biohydrogen from microalgae, the economic feasibility remains the most important
      aspect to consider. Several technological and economic issues must be addressed
      to achieve success on a commercial scale.

PMID- 29444682
TI  - Serum IgG subclass levels and risk of exacerbations and hospitalizations in
      patients with COPD.
AB  - BACKGROUND: The literature is scarce regarding the prevalence and clinical impact
      of IgG subclass deficiency in COPD. We investigated the prevalence of IgG
      subclass deficiencies and their association with exacerbations and
      hospitalizations using subjects from two COPD cohorts. METHODS: We measured IgG
      subclass levels using immunonephelometry in serum samples from participants
      enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of
      Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of
      Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653). All samples were
      collected from clinically stable participants upon entry into both studies. IgG
      subclass deficiency was diagnosed when IgG subclass levels were below their
      respective lower limit of normal: IgG1 < 2.8 g/L; IgG2 < 1.15 g/L; IgG3 < 0.24
      g/L; and IgG4 < 0.052 g/L. To investigate the impact of IgG subclass levels on
      time to first exacerbation or hospitalization, we log-transformed IgG levels and
      performed Cox regression models, with adjustments for confounders. RESULTS: One
      or more IgG subclass deficiencies were found in 173 (17.7%) and 133 (20.4%)
      participants in MACRO and STATCOPE, respectively. Lower IgG1 or IgG2 levels
      resulted in increased risk of exacerbations with adjusted hazard ratios (HR) of
      1.30 (95% CI, 1.10-1.54, p < 0.01) and 1.19 (95% CI, 1.05-1.35, p < 0.01),
      respectively in the MACRO study, with STATCOPE yielding similar results. Reduced
      IgG1 or IgG2 levels were also associated with increased risk of hospitalizations:
      the adjusted HR for IgG1 and IgG2 was 1.52 (95% CI: 1.15-2.02, p < 0.01) and 1.33
      (95% CI, 1.08-1.64, p < 0.01), respectively for the MACRO study; in STATCOPE,
      only IgG2 was an independent predictor of hospitalization. In our multivariate
      Cox models, IgG3 and IgG4 levels did not result in significant associations for
      both outcomes in either MACRO or STATCOPE cohorts. CONCLUSIONS: Approximately 1
      in 5 COPD patients had one or more IgG subclass deficiencies. Reduced IgG
      subclass levels were independent risk factors for both COPD exacerbations (IgG1
      and IgG2) and hospitalizations (IgG2) in two COPD cohorts. TRIAL REGISTRATION:
      This study used serum samples from participants of the MACRO ( NCT00325897 ) and
      STATCOPE ( NCT01061671 ) trials.

PMID- 29444683
TI  - Potential effects of the combination of nicotinamide, vitamin B2 and vitamin C on
      oxidative-mediated hepatotoxicity induced by thioacetamide.
AB  - BACKGROUND: The liver disease is one of the most important traditional public
      health problems in Egypt. Oxidative stress is attributed to such pathological
      condition that further contributes to the initiation and progression of liver
      injury. In the present study, we have investigated if the strong antioxidant
      power of Nicotinamide (NA), Vitamin B2 (VB2), and Vitamin C (VC) can ameliorate
      TAA-induced oxidative stress-mediated liver injury in the rats. METHODS: Thirty
      six albino rats were divided into six groups: Control group; TAA group (IP
      injection with TAA at a dosage of 200 mg/Kg three times a week for two months);
      TAA + NA group (rats administered with NA at a dosage of 200 mg/kg daily besides
      TAA as in the control); TAA + VB2 group (rats administered with vitamin B2 at a
      dosage of 30 mg/kg daily besides injection with TAA); TAA + VC group (rats
      administered with vitamin C at a dosage of 200 mg/kg daily along with injection
      of TAA). TAA + NA + VB + VC group (rats administered the with the three vitamins
      daily in TAA pre-injected at the respective doses described above). RESULTS:
      Treatment of rats with TAA led to a significant elevation of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase
      (ALP), lactate dehydrogenase (LDH), total bilirubin, cholesterol, triglycerides,
      low-density lipoprotein (LDL) and tumor necrosis factor-alpha (TNF-alpha) in the
      serum samples. Moreover, malondialdehyde (MDA), hydroxyproline and nitic oxide
      (NO) were also significantly increased in the TAA-treated rats, while reduced
      glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were
      significantly compromised in the hepatic samples. Rats administered with NA, VB2,
      and VC as individually or in combination ameliorated the deleterious effects of
      TAA that was confirmed by histopathology. However, the combination of the three
      vitamins was found more effective as compared to each of the vitamins.
      CONCLUSION: Our work demonstrates that NA, VB2, and VC cross-talk with each other
      that act as a more potent biochemical chain of antioxidant defense against TAA
      induced toxicities in vivo.

PMID- 29444684
TI  - Medicinal plants used by traditional healers to treat malignancies and other
      human ailments in Dalle District, Sidama Zone, Ethiopia.
AB  - BACKGROUND: Medicinal plants (MPs) used by traditional healers (THs) were
      investigated in Megera and adjacent subdistricts (kebeles) of Dalle District,
      Sidama Zone, southern Ethiopia. The objective of the study was to identify and
      record MPs and their traditional uses in the treatment of various human ailments
      with emphasis on malignancies and other most frequently reported diseases.
      METHODS: Traditional medicinal knowledge held by 20 THs was investigated
      following standard ethnobotanical approaches. Guided field walk, free listing,
      rigorous individual interviews with extended discussions, and local market
      surveys were employed to obtain information. Preference rankings, paired
      comparisons, use value (UV) index, frequency of citation (FC), fidelity level
      (FL), and informant consensus factor (ICF) matrices were engaged to identify MPs
      used to treat malignancies and the other most prevalent human ailments. RESULTS:
      Seventy-one MP species belonging to 63 genera and 46 families, used to treat 39
      human ailments, were recorded. A high proportion of the species recovered was
      shrubs (35.2%); while 64.7% were retrieved from the wild habitat. Leaves were the
      main part of the MPs used (42.9%), followed by fruits/seeds (13%); all
      preparations were made from fresh materials and about 27.9% involved boiling. The
      frequent route of delivery was oral (77.9%), followed by dermal (17.6%). About
      40.8% of the MPs were used for treating two or more ailments. About 19.7% of the
      MPs were used to treat malignancies (ICF = 0.86) among which the plant species
      Sideroxylon oxyacanthum was the most frequently used (FL = 70%). The species
      Podocarpus falcatus and Hagenia abyssinica were preferred to treat jaundice and
      deworm in helminthiases, respectively. CONCLUSION: The study area is very rich in
      plant biodiversity, and the herbal medicine is an integral part of the
      traditional healthcare system. The MPs are exposed to various destructive
      anthropogenic activities, and this situation calls for integrated conservation
      measures. Furthermore, the rich ethnomedicinal knowledge held by the Sidama
      community at large and TM practitioners, in particular, needs an in-depth study
      and documentation. Investigations of the MPs with high ICF, FL, and UVs to
      malignancies, jaundice, and helminthiases could possibly contribute to future
      drug development efforts.

PMID- 29444685
TI  - Prevalence and correlates of HIV infection among men who inject drugs in a remote
      area of Vietnam.
AB  - BACKGROUND: Lack of information on the HIV epidemic among men who inject drugs
      (MWID) in northwestern Vietnam, a remote area, may hamper national efforts to
      control the disease. We examined HIV prevalence, needle-syringe sharing
      behaviors, and associated factors among MWID in three areas of northwestern
      Vietnam. METHODS: We used descriptive analysis to report the characteristics,
      frequency of risk behaviors, and of access to healthcare services among the MWID.
      Univariable logistic regression was used to assess the associations between the
      HIV infection, needle-syringe sharing behaviors, and their independent variables.
      We further explored these associations in multivariable analyses where we
      included independent variables based on a priori knowledge and their associations
      with the dependent variables determined in univariable analyses (p <  0.25).
      RESULTS: The HIV prevalence was 37.9, 16.9, and 18.5% for Tuan Giao, Bat Xat, and
      Lao Cai City, respectively, and 25.4% overall. MWID of Thai minority ethnicity
      were more likely to be HIV-positive (adjusted odds ratio (AOR) 3.55; 95%
      confidence interval (CI) 1.84-6.87). The rate of needle-syringe sharing in the
      previous 6 months was approximately 9% among the MWID in Tuan Giao and Lao Cai
      City, and 27.8% in Bat Xat. Two thirds of the participants never underwent HIV
      testing before this study. Ever having been tested for HIV before this study was
      not associated with any needle-syringe sharing behaviors. Among the HIV-positive
      MWID, those who received free clean needles and syringes were less likely to give
      used needles and syringes to peers (AOR 0.21; 95% CI 0.06-0.79). Going to a
      "hotspot" in the previous week was associated with increased odds of needle
      syringe sharing in multiple subgroups. CONCLUSION: Our findings on HIV prevalence
      and testing participation among a subset of MWID in the northwestern Vietnam were
      corroborated with trend analysis results from the most recent HIV/STI Integrated
      Biological and Behavioral Surveillance report (data last collected in 2013.) We
      provided important insights into these MWID's risky injection behaviors. We
      suggest heightened emphasis on HIV testing and needle and syringe provision for
      this population. Also, policymakers and program implementers should target
      hotspots as a main venue to tackle HIV epidemics.

PMID- 29444686
TI  - Cumulative incidence, distribution, and determinants of catastrophic health
      expenditure in Nepal: results from the living standards survey.
AB  - BACKGROUND: Nepal has committed to the global community to achieve universal
      health coverage by 2030. Nevertheless, Nepal still has a high proportion of out
      of-pocket health payment and a limited risk-pooling mechanism. Out-of-pocket
      payment for the healthcare services could result in catastrophic health
      expenditure (CHE). Evidence is required to effectively channel the efforts to
      lower those expenses in order to achieve universal health coverage. However,
      little is known about CHE and its determinants in a broad national context in
      Nepal. Therefore, this study was conducted to explore the cumulative incidence,
      distribution, and determinants of CHE in Nepal. METHODS: Data were obtained from
      the nationally representative survey, the Nepal Living Standards Survey-third
      undertaken in 2010/11. Information from 5988 households was used for the
      analyses. Households were classified as having CHE when their out-of-pocket
      health payment was greater than or equal to 40% of their capacity to pay.
      Remaining households were classified as not having CHE. Logistic regression
      analyses were used to identify determinants of CHE. RESULTS: Based on household
      weighted sample, the cumulative incidence of CHE was 10.3% per month in Nepal.
      This incidence was concentrated in the far-western region and households in the
      poorer expenditure quartiles. Multivariable logistic regression revealed that
      households were more likely to face CHE if they; consisted of chronically ill
      member(s), have a higher burden of acute illness and injuries, have elderly (>=60
      years) member(s), belonged to the poor expenditure quartile, and were located in
      the far-western region. In contrast, households were less likely to incur CHE
      when their household head was educated. Having children (<=5 years) in households
      did not significantly affect catastrophic health expenditure. CONCLUSIONS: This
      study identified a high cumulative incidence of CHE. CHE was disproportionately
      concentrated in the poor households and households located in the far-western
      region. Policy-makers should focus on prioritizing households vulnerable to CHE.
      Interventions to reduce economic burden of out-of-pocket healthcare payment are
      imperative to lower incidences of CHE among those households. Improving literacy
      rate might also be useful in order to lower CHE and facilitate universal health
      coverage.

PMID- 29444687
TI  - Psychometric properties of the medical outcomes study: social support survey
      among methadone maintenance patients in Ho Chi Minh City, Vietnam: a validation
      study.
AB  - BACKGROUND: Social support plays a crucial role in the treatment and recovery
      process of patients engaging in methadone maintenance treatment (MMT). However,
      there is a paucity of research about social support among MMT patients, possibly
      due to a lack of appropriate measuring tools. This study aimed to evaluate the
      psychometric properties of the Vietnamese version of the Medical Outcomes Study:
      Social Support Survey (MOS-SSS) among MMT patients. METHODS: A cross-sectional
      survey of 300 patients was conducted in a methadone clinic in Ho Chi Minh City,
      Vietnam. MMT patients who agreed to participate in the study completed a face-to
      face interview in a private room. The MOS-SSS was translated into Vietnamese
      using standard forward-backward process. Internal consistency was measured by
      Cronbach's alpha. The intra-class correlation coefficient was used to determine
      the test-retest reliability of the MOS-SSS in 75 participants two weeks after the
      first survey. Concurrent validity of the MOS-SSS was evaluated by correlations
      with the Multidimensional Scale of Perceived Social Support (MSPSS) and the
      Perceived Stigma of Addiction Scale (PSAS). Construct validity was investigated
      by confirmatory factor analysis. RESULTS: The MOS-SSS had good internal
      consistency with Cronbach's alpha from 0.95 to 0.97 for the four subscales and
      0.97 for the overall scale. The two-week test-retest reliability was at moderate
      level with intra-class correlation coefficients of 0.61-0.73 for the four
      subscales and 0.76 for the overall scale. Strong significant correlations between
      the MOS-SSS and the MSPSS (r = 0.77; p < 0.001) and the PSAS (r = - 0.76; p <
      0.001) indicated good concurrent validity. Construct validity of the MOS-SSS was
      established since a final four-factor model fitted the data well with Comparative
      Fit Index (0.97), Tucker-Lewis Index (0.97), Standardized Root Mean Square
      Residual (0.03) and Root Mean Square Error of Approximation (0.068; 90% CI =
      0.059-0.077). CONCLUSIONS: The MOS-SSS is a reliable and valid tool for measuring
      social support in Vietnamese MMT patients. Further studies among methadone
      patients at different stages of their treatment and among those from different
      areas of Vietnam are needed.

PMID- 29444689
TI  - Comprehensive knowledge on cervical cancer, attitude towards its screening and
      associated factors among women aged 30-49 years in Finote Selam town, northwest
      Ethiopia.
AB  - BACKGROUND: Screening services for cervical pre-cancerous lesions is currently
      available for all women aged 30-49 years at public hospitals in Ethiopia. Though
      women's knowledge and their attitude are determinants for the uptake the
      screening service, there is limited information on these regards. Therefore, this
      study aimed to assess comprehensive knowledge on cervical cancer, attitudes
      towards the screening, and associated factors among women aged 30-49 years at
      Finote Selam town, northwest Ethiopia. METHODS: A community based cross-sectional
      study was conducted from March 30, to April 15, 2017. The sample size calculated
      for this study was 1224 and a cluster sampling technique was used to select the
      participants from three randomly selected kebeles. Epi-Info version 7 and
      Statistical Package for Social Sciences version 20 were used for data entry and
      analysis respectively. A binary logistic regression model was used. In
      multivariable logistic analysis, adjusted odds ratio with a 95% confidence
      interval was used to determine the presence and strength of associations between
      covariate and outcome variable. RESULTS: A total of 1137 women participated in
      this study. Nearly one third, 30.3% (95%CI: 27.7, 32.9) of the women had
      knowledge of cervical cancer, and 58.1% (95% CI: 55, 62.2) had a favorable
      attitude towards cervical cancer screening. In the multivariable analysis, having
      college and above education (AOR = 7.21, 95%CI: 3.41, 15.29), knowing someone
      with cervical cancer (AOR =5.38, 95%CI: 2.38, 12.15), and having a history of
      sexually transmitted diseases (AOR = 2.75, 95%CI: 1.24, 6.04) were significantly
      associated with knowledge on cervical cancer. Meanwhile, college and above
      educational status (AOR = 2.56, 95%CI: 1.14, 5.69), knowing someone with cervical
      cancer (AOR = 3.24, 95%CI: 1.14, 9.15), and having knowledge of cervical cancer
      (AOR = 3, 95%CI: 1.97, 4.29) were positively associated with favorable attitudes
      towards cervical cancer screening. CONCLUSION: The proportion of women who had
      knowledge on cervical cancer was low where as relatively, a large proportion of
      the study participants in this study had favorable attitude towards cervical
      cancer screening. Educational status, knowing someone with cervical cancer, a
      history of sexually transmitted diseases was factors affecting both women's
      knowledge and their attitude. Having knowledge on cervical cancer was factor
      affecting attitude towards screening services. Provision of information,
      education, and counseling about the disease and screening service are mandatory
      to address their knowledge gap and to improve women's attitude towards screening
      service.

PMID- 29444688
TI  - Twenty years of home-based palliative care in Malappuram, Kerala, India: a
      descriptive study of patients and their care-givers.
AB  - BACKGROUND: The well lauded community-based palliative care programme of Kerala,
      India provides medical and social support, through home-based care, for patients
      with terminal illness and diseases requiring long-term support. There is,
      however, limited information on patient characteristics, caregivers and programme
      performance. This study was carried out to describe: i) the patients enrolled in
      the programme from 1996 to 2016 and their diagnosis, and ii) the care-giver
      characteristics and palliative care support from nurses and doctors in a cohort
      of patients registered during 2013-2015. METHODS: A descriptive study was
      conducted in the oldest community-based palliative clinic in Kerala. Data were
      collected from annual patient registers from 1996 to 2016 and patient case
      records during the period 2013-2015. RESULTS: While 91% of the patients
      registered in the clinic in 1996 had cancer, its relative proportion came down to
      32% in 2016 with the inclusion of dementia-related illness (19%) cardiovascular
      accidents (17%) and severe mental illness (5%).Among patients registered during
      2013-15, the median number of home visits from nurses and doctors in 12 months
      were five and one respectively. In the same cohort, twelve months' post
      enrolment, 56% of patients died, 30% were in continuing in active care and 7%
      opted out. Those who opted out of care were likely to be aged < 60 years,
      received one or less visit annually from a doctor or have a serious mental
      illness. 96% of patients had a care-giver at home, 85% of these care-givers being
      female. CONCLUSIONS: The changing dynamics over a 20-year period of this
      palliative care programme in Kerala, India, highlights the need for similar
      programmes to remain flexible and adapt their services in response to a growing
      global burden of Non Communicable Diseases. While a high death rate is expected
      in this population, the high proportion of patients choosing to stay in the
      programme suggests that home-based care is valued within this particular group. A
      diverse range of clinical and psycho-social support skills are required to assist
      families and their caregivers when caring for a cohort such as this one.

PMID- 29444690
TI  - Efficacy of N,N'bis-(2-mercaptoethyl) isophthalamide on mercury intoxication: a
      randomized controlled trial.
AB  - BACKGROUND: Chronic mercury intoxication is a severe health issue and occurs
      especially in gold mining communities. Common chelators used for improving
      mercury elimination are not everywhere available and challenged by poor cell wall
      penetration. This study is part of a feasibility trial and the aim was to gather
      first information about the efficacy of the newly developed chelator N,N'bis-(2
      mercaptoethyl) isophthalamide (NBMI) on chronic mercury intoxication. METHODS: In
      this three-armed, placebo-controlled randomized trial, 36 miners with mercury
      urine levels exceeding 15 MUg/l were administered 100 mg NBMI, 300 mg NBMI or
      placebo for 14 days. Levels of mercury in urine [MUg/l and MUg/g creatinine] and
      plasma l were analyzed. Therapeutic effect was assessed using the medical
      intoxication score (MIS) and its single health outcomes (e.g. excessive
      salivation, sleeping problems), fatigue scores, a neuromotoric test battery
      (CATSYS) and a neurological outcome (Finger to nose test). RESULTS: Physical
      fatigue was significantly decreased in the 300 mg NBMI group compared to the
      control. Mercury concentration in urine following 300 mg NBMI treatment was
      significantly lowered compared to control, however, this effect was less distinct
      with adjustment for creatinine. CONCLUSION: NBMI showed an effect on physical
      fatigue and there were indications to positive effects on other symptoms as well.
      More comprehensive studies are mandatory to verify the effects of NBMI as a novel
      tool for treating mercury intoxications. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT02486289 . Date of registration: June 24, 2015.

PMID- 29444691
TI  - Affinity proteomic profiling of plasma for proteins associated to area-based
      mammographic breast density.
AB  - BACKGROUND: Mammographic breast density is one of the strongest risk factors for
      breast cancer, but molecular understanding of how breast density relates to
      cancer risk is less complete. Studies of proteins in blood plasma, possibly
      associated with mammographic density, are well-suited as these allow large-scale
      analyses and might shed light on the association between breast cancer and breast
      density. METHODS: Plasma samples from 1329 women in the Swedish KARMA project,
      without prior history of breast cancer, were profiled with antibody suspension
      bead array (SBA) assays. Two sample sets comprising 729 and 600 women were
      screened by two different SBAs targeting a total number of 357 proteins. Protein
      targets were selected through searching the literature, for either being related
      to breast cancer or for being linked to the extracellular matrix. Association
      between proteins and absolute area-based breast density (AD) was assessed by
      quantile regression, adjusting for age and body mass index (BMI). RESULTS: Plasma
      profiling revealed linear association between 20 proteins and AD, concordant in
      the two sets of samples (p < 0.05). Plasma levels of seven proteins were
      positively associated and 13 proteins negatively associated with AD. For eleven
      of these proteins evidence for gene expression in breast tissue existed. Among
      these, ABCC11, TNFRSF10D, F11R and ERRF were positively associated with AD, and
      SHC1, CFLAR, ACOX2, ITGB6, RASSF1, FANCD2 and IRX5 were negatively associated
      with AD. CONCLUSIONS: Screening proteins in plasma indicates associations between
      breast density and processes of tissue homeostasis, DNA repair, cancer
      development and/or progression in breast cancer. Further validation and follow-up
      studies of the shortlisted protein candidates in independent cohorts will be
      needed to infer their role in breast density and its progression in premenopausal
      and postmenopausal women.

PMID- 29444692
TI  - Western and Modern Mexican dietary patterns are directly associated with incident
      hypertension in Mexican women: a prospective follow-up study.
AB  - BACKGROUND: Research has found that diet and dietary patterns are associated with
      blood pressure and hypertension. Limited research in this area has been conducted
      in a Mexican population. METHODS: We investigated the relation between dietary
      patterns (principal component analysis) and the incidence of self-reported
      treated hypertension in 62,913 women from the Mexican Teachers' Cohort, a large
      population-based cohort of female Mexican teachers, who were free of hypertension
      at baseline in 2006-2008 when diet was assessed using a food frequency
      questionnaire. Dietary patterns were categorized into quartiles and logistic
      regression models were fit. RESULTS: Participants were 42.1 +/- 7.3 years old,
      had a BMI 27.0 +/- 4.4 and a cumulative incidence of hypertension of 4.6%.
      Between baseline and first follow-up (2011-2014) we identified 2916 incident
      cases of hypertension. We identified three major components. The first was loaded
      heavily with vegetables, fruits and legumes; the second component was loaded
      heavily with processed meats, fast foods, and red meat; and finally the third
      component was loaded heavily with corn tortillas, hot peppers, and sodas. We
      named the components as Fruits & Vegetables (FV), Western (W), and Modern Mexican
      (MM). The multivariable-adjusted odds of hypertension in the highest quartile of
      the W pattern were 24% higher than the odds for individuals in the lowest
      quartile (95%CI = 1.10, 1.40; P-trend = 0.0004); women in the highest quartile of
      the MM pattern had 15% higher odds than women in the lowest quartile (95%CI =
      1.02, 1.29; P-trend = 0.01). The FV pattern was not significantly associated with
      hypertension (OR for extreme quartiles = 0.94; 95%CI = 0.84, 1.05; P-trend =
      0.19). CONCLUSION: The Western pattern and the Modern Mexican pattern, which
      showcases an undergoing nutrition transition, may affect the incidence of
      hypertension, whereas the FV pattern was not associated with hypertension. These
      findings are important in the prevention of hypertension and cardiovascular
      diseases in Mexico and possibly among Mexican people living in the US.

PMID- 29444693
TI  - Monitoring of mechanical errors and their dosimetric impact throughout the course
      of non-coplanar continuous volumetric-modulated arc therapy.
AB  - BACKGROUND: Volumetric-modulated Dynamic WaveArc therapy (VMDWAT) is a non
      coplanar continuous volumetric modulated radiation therapy (VMAT) delivery
      technique. Here, we monitored mechanical errors and their impact on dose
      distributions in VMDWAT using logfiles throughout the course of treatment.
      METHODS: Fifteen patients were enrolled (2 skull base tumor patients and 13
      prostate cancer patients). VMDWAT plans were created for the enrolled patients.
      The prescribed dose for the skull base tumor was set as 54 Gy at 1.8 Gy per
      fraction, and that for the prostate cancer was set as 72 to 78 Gy at 2 Gy per
      fraction. We acquired logfiles to monitor mechanical errors and their impact on
      dose distribution in each fraction. The root mean square error (RMSE) in the
      multi-leaf collimator (MLC), gantry angle, O-ring angle and monitor unit (MU)
      were calculated using logfiles throughout the course of VMDWAT for each patient.
      The dosimetric impact of mechanical errors throughout the course of VMDWAT was
      verified using a logfile-based dose reconstruction method. Dosimetric errors
      between the reconstructed plans and the original plans were assessed. RESULTS: A
      total of 517 datasets, including 55 datasets for the 2 skull base tumor patients
      and 462 datasets for the 13 prostate cancer patients, were acquired. The RMSE
      values were less than 0.1 mm, 0.2 degrees , 0.1 degrees , and 0.4 MU for MLC
      position, gantry angle, O-ring angle, and MU, respectively. For the skull base
      tumors, the absolute mean dosimetric errors and two standard deviations
      throughout the course of treatment were less than 1.4% and 1.1%, respectively.
      For prostate cancer, these absolute values were less than 0.3% and 0.5%,
      respectively. The largest dosimetric error of 2.5% was observed in a skull base
      tumor patient. The resultant dosimetric error in the accumulated daily delivered
      dose distribution, in the patient with the largest error, was up to 1.6% for all
      dose-volumetric parameters relative to the planned dose distribution.
      CONCLUSIONS: MLC position, gantry rotation, O-ring rotation and MU were highly
      accurate and stable throughout the course of treatment. The daily dosimetric
      errors due to mechanical errors were small. VMDWAT provided high delivery
      accuracy and stability throughout the course of treatment. TRIAL REGISTRATION:
      UMIN000023870 . Registered: 1 October 2016.

PMID- 29444694
TI  - Reliability and construct validity of the Ottawa valve collapse scale when
      assessing external nasal valve collapse.
AB  - BACKGROUND: Nasal valve collapse is a common cause of nasal obstruction in
      otolaryngology practice. Common examination methods, such as the Cottle Maneuver
      and modified Cottle Maneuver are available. However, these methods are
      dichotomous and do not provide ordinal severity information. The Ottawa Valve
      Collapse Scale (OVCS) is a grading system for assessing and easily grading
      external nasal valve collapse in patients with a septal deviation. The primary
      objective was to assess the test-retest reliability and construct validity of the
      OVCS grading scale. A secondary objective was to perform the same assessments on
      the Cottle Maneuver. METHODS: Patients with a septal deviation who were
      requesting surgical correction were prospectively enrolled in the study. All
      patients were assessed using both the Cottle Maneuver and the OVCS by one
      otolaryngologist at two visits separated by one month. The phi coefficient was
      calculated to assess the test-retest reliability of the instruments. Results of
      the Nasal Obstruction Symptom Evaluation (NOSE) Score was compared to determine
      construct validity. RESULTS: Ninety-two patients met our inclusion criteria. The
      phi coefficient was 0.62 for the OVCS and 0.32 for the Cottle Maneuver. The
      scores on the NOSE instrument were positively associated with the OVCS scores (p
      = 0.01) while there was no association with the Cottle Maneuver (p = 047).
      CONCLUSION: This current preliminary analysis suggests that the novel Ottawa
      Valve Collapse Scale has good test-retest reliability and construct validity.
      This scale may help clinicians grade external nasal valve collapse in patients
      with a septal deviation. Future studies are required to determine if this scale
      assists surgeons in determining which patients need formal nasal valve surgery in
      addition to a standard septoplasty.

PMID- 29444695
TI  - The impact of manual rotation of the occiput posterior position on spontaneous
      vaginal delivery rate: study protocol for a randomized clinical trial (RMOS).
AB  - BACKGROUND: The frequency of posterior presentations (occiput of the fetus
      towards the sacrum of the mother) in labor is approximately 20% and, of this, 5%
      remain posterior until the end of labor. These posterior presentations are
      associated with higher rates of cesarean section and instrumental delivery.
      Manual rotation of a posterior position in order to rotate the fetus to an
      anterior position has been proposed in order to reduce the rate of instrumental
      fetal delivery. No randomized study has compared the efficacy of this procedure
      to expectant management. We therefore propose a monocentric, interventional,
      randomized, prospective study to show the superiority of vaginal delivery rates
      using the manual rotation of the posterior position at full dilation over
      expectant management. METHODS: Ultrasound imaging of the presentation will be
      performed at full dilation on all the singleton pregnancies for which a clinical
      suspicion of a posterior position was raised at more than 37 weeks' gestation
      (WG). In the event of an ultrasound confirming a posterior position, the patient
      will be randomized into an experimental group (manual rotation) or a control
      group (expectative management with no rotation). For a power of 90% and the
      hypothesis that vaginal deliveries will increase by 20%, (10% of patients lost to
      follow-up) 238 patients will need to be included in the study. The primary
      endpoint will be the rate of spontaneous vaginal deliveries (expected rate
      without rotation: 60%). The secondary endpoints will be the rate of fetal
      extractions (cesarean or instrumental) and the maternal and fetal morbidity and
      mortality rates. The intent-to-treat study will be conducted over 24 months.
      Recruitment started in February 2017. To achieve the primary objective, we will
      perform a test comparing the number of spontaneous vaginal deliveries in the two
      groups using Pearson's chi-squared test (provided that the conditions for using
      this test are satisfactory in terms of numbers). In the event that this test
      cannot be performed, we will use Fisher's exact test. DISCUSSION: Given that the
      efficacy of manual rotation has not been proven with a high level of evidence,
      the practice of this technique is not systematically recommended by scholarly
      societies and is, therefore, rarely performed by obstetric gynecologists. If our
      hypothesis regarding the superiority of manual rotation is confirmed, our study
      will help change delivery practices in cases of posterior fetal position. An
      increase in the rates of vaginal delivery will help decrease the short- and long
      term rates of morbidity and mortality following cesarean section. Manual rotation
      is a simple and effective method with a success rate of almost 90%. Several
      preliminary studies have shown that manual rotation is associated with reduced
      rates for fetal extraction and maternal complications: Shaffer has shown that the
      cesarean section rate is lower in patients for whom a manual rotation is
      performed successfully (2%) with a 9% rate of cesarean sections when manual
      rotation is performed versus 41% when it is not performed. Le Ray has shown that
      manual rotation significantly reduces vaginal delivery rates via fetal extraction
      (23.2% vs 38.7%, p < 0.01). However, manual rotation is not systematically
      performed due to the absence of proof of its efficacy in retrospective studies
      and quasi-experimental before/after studies. TRIAL REGISTRATION:
      ClinicalTrials.gov, Identifier: NCT03009435 . Registered on 30 December 2016.

PMID- 29444696
TI  - Bedside analysis of the sublingual microvascular glycocalyx in the emergency room
      and intensive care unit - the GlycoNurse study.
AB  - BACKGROUND: Deterioration of the endothelial glycocalyx (eGC), a protective
      carbohydrate-rich layer lining the luminal surface of the endothelium, plays a
      key role in vascular barrier dysfunction and eventually organ-failure in systemic
      inflammatory response syndrome and sepsis. Early detection of glycocalyx damage
      could thus become an important goal in critical care. This study was designed to
      determine the feasibility and reproducibility of quantitative, real-time
      glycocalyx measurements performed at bedside in the emergency room (ER) and
      intensive care unit (ICU). METHODS: The observational study included 70 patients
      admitted to the ER or ICU of a university hospital. A physician and the nurse in
      charge of the patient performed sublingual microcirculatory measurements using
      sidestream dark field (SDF) imaging. A novel data acquisition and analysis
      software (GlycoCheckTM) was used to analyze the perfused boundary region (PBR),
      an inverse parameter of endothelial glycocalyx dimensions in vessels with
      diameters of between 5 and 25 MUm. RESULTS: The method showed a good intra
      observer reproducibility. Specifically, intraclass correlation coefficient
      analysis showed an excellent reproducibility between the physician's measurements
      (0.77 [CI 95%: 0.52-0.89]). The bias between the two PBRs was - 0.077 +/- 0.24
      MUm. Moreover, there were no significant differences in the PBR values obtained
      by the nurses when compared to those reported by the physician (regarded as the
      "gold standard" measurement). Intraclass correlation coefficient analysis showed
      excellent reproducibility between the nurses' and physician's PBRs (0.75 [95% CI:
      0.52-0.87]). The mean difference between the two PBRs (i.e., the bias) was 0.007
      +/- 0.25 MUm. The nurses' PBR assessment had a 90% sensitivity (95% CI: 60-99%)
      and 90% specificity (95% CI: 80-93%) to identify a severely impaired glycocalyx.
      CONCLUSION: Glycocalyx dimensions can be measured at patients' bedside precisely
      by non-invasive assessment of the PBR. This assessment could become part of
      standard monitoring and contribute to clinical decision-making and resuscitation
      protocols in clinical trials and daily practice.

PMID- 29444697
TI  - Modulation of pro-apoptotic effects and mitochondrial potential on B16F10 cells
      by DODAC/PHO-S liposomes.
AB  - OBJECTIVE: We aimed to evaluate the potential of DODAC/PHO-S liposomes on the
      modulation of the expression of pro-apoptotic proteins, loss of lysosomal
      integrity and the mitochondrial electrical potential, compared with
      phosphoethanolamine. RESULTS: The results of this study demonstrate that
      DODAC/PHO-S liposomes have exhibited broad cytotoxic potential in B16F10 murine
      melanoma cells, with significantly greater proportions than treatment with PHO-S.
      The treatment with the DODAC/PHO-S 2.0 mM liposomal formulation was more
      efficient in decreasing mitochondrial electrical potential at the same
      concentrations and treatment time than PHO-S The liposomal formulation DODAC/PHO
      S (2.0 mM) was more efficient to promote morphological changes in the cells,
      without presenting intact lysosomes, at the same time of treatment and
      concentration as PHO-S Our results demonstrated that the liposomal formulation
      increased DR4 receptor expression and activated caspases 8 and 3, resulting in
      the release of cytochrome c in B16F10 tumour cells, when compared to treatment
      with PHO-S The data obtained prove that the use of DODAC as carrier can maximize
      the cytotoxic effects of PHO-S This was demonstrated by the translocation of
      cytochrome c to the cytoplasm and activation of caspase-3 and 8, decreasing the
      mitochondrial electrical potential and generating morphological changes, in
      B16F10 cells.

PMID- 29444698
TI  - Using OWL reasoning to support the generation of novel gene sets for enrichment
      analysis.
AB  - BACKGROUND: The Gene Ontology (GO) consists of over 40,000 terms for biological
      processes, cell components and gene product activities linked into a graph
      structure by over 90,000 relationships. It has been used to annotate the
      functions and cellular locations of several million gene products. The graph
      structure is used by a variety of tools to group annotated genes into sets whose
      products share function or location. These gene sets are widely used to interpret
      the results of genomics experiments by assessing which sets are significantly
      over- or under-represented in results lists. F Hoffmann-La Roche Ltd. has
      developed a bespoke, manually maintained controlled vocabulary (RCV) for use in
      over-representation analysis. Many terms in this vocabulary group GO terms in
      novel ways that cannot easily be derived using the graph structure of the GO. For
      example, some RCV terms group GO terms by the cell, chemical or tissue type they
      refer to. Recent improvements in the content and formal structure of the GO make
      it possible to use logical queries in Web Ontology Language (OWL) to
      automatically map these cross-cutting classifications to sets of GO terms. We
      used this approach to automate mapping between RCV and GO, largely replacing the
      increasingly unsustainable manual mapping process. We then tested the utility of
      the resulting groupings for over-representation analysis. RESULTS: We
      successfully mapped 85% of RCV terms to logical OWL definitions and showed that
      these could be used to recapitulate and extend manual mappings between RCV terms
      and the sets of GO terms subsumed by them. We also show that gene sets derived
      from the resulting GO terms sets can be used to detect the signatures of cell and
      tissue types in whole genome expression data. CONCLUSIONS: The rich formal
      structure of the GO makes it possible to use reasoning to dynamically generate
      novel, biologically relevant groupings of GO terms. GO term groupings generated
      with this approach can be used in. over-representation analysis to detect cell
      and tissue type signatures in whole genome expression data.

PMID- 29444699
TI  - The HYSTER study: the effect of intracervically administered terlipressin versus
      placebo on the number of gaseous emboli and fluid intravasation during
      hysteroscopic surgery: study protocol for a randomized controlled clinical trial.
AB  - BACKGROUND: Transcervical resection of myoma or endometrium is a safe,
      hysteroscopic, minimally invasive procedure. However, intravasation of distension
      fluid is a common phenomenon during these procedures. In a previous study we
      observed venous gas emboli in almost every patient. The severity of hysteroscopic
      derived embolization has been shown to be correlated to the amount of
      intravasation. In addition, paradoxical gas embolism, which is potentially
      dangerous, was observed in several patients. Studies have shown a reduction of
      intravasation by using intracervically administered vasopressin during
      hysteroscopy. We think that its analog, terlipressin, should have the same
      effect. In our previous research we observed more gaseous emboli as intravasation
      increased. Whether or not the insertion of intracervically administered
      terlipressin leads to a lower incidence and severity of gas embolism is unknown.
      We hypothesize that intracervically administered terlipressin leads to a
      reduction of intravasation with a lower incidence and severity of gas embolism.
      Terlipressin may be of benefit during hysteroscopic surgery. METHODS/DESIGN:
      Forty-eight patients (ASA 1 or 2) scheduled for transcervical resection of large,
      types 1-2 myoma or extensive endometrium resection will be included. In a double
      blind fashion patients will be randomized 1:1 according to surgical treatment
      using either intracervically administered terlipressin or placebo.
      Transesophageal echocardiography will be used to observe and record embolic
      events. A pre- and post-procedure venous blood sample will be taken to calculate
      intravasation based on hemodilution. Our primary endpoint will be how
      terlipressin influences the severity of embolic events. Secondary endpoints
      include the effect of terlipressin on the amount of intravasation and on
      hemodynamic parameters. DISCUSSION: If terlipressin does indeed reduce the number
      of gaseous emboli and intravasation occurring during hysteroscopic surgery, it
      would be a simple method to minimize potential adverse events. It also allows for
      prolonged operating time before the threshold of intravasation is reached,
      thereby reducing the need for a second operation. TRIAL REGISTRATION: Nederlands
      Trial Register (Dutch Trial Register), ID: NTR5577 . Registered retrospectively
      on 18 December 2015.

PMID- 29444700
TI  - Pharmacotherapies for fatigue in chronic liver disease (CLD): a systematic review
      and meta-analysis (protocol).
AB  - BACKGROUND: This is the protocol for a systematic review (and meta-analysis) of
      an intervention. The primary objective of this systematic review will be to
      assess the benefits and harms of pharmacological therapies (pharmacotherapies)
      for the management of fatigue in adults with CLD of any etiology. The effects of
      pharmacological therapies on fatigue in CLD will be compared against those of
      placebo, no intervention, or non-pharmacological interventions. Specifically,
      this review will examine whether pharmacological therapies improve CLD-associated
      fatigue, and if they do, what key elements are associated with their
      effectiveness. The results of this systematic review will assist clinicians,
      policy-makers, researchers, and people with CLD in decision-making on how best to
      manage fatigue and its associated symptoms. METHODS: MEDLINE, SCOPUS, EMBASE, EU
      Clinical Trials Register, WHO International Clinical Trials Registry Platform,
      CENTRAL (The Cochrane Library), ClinicalTrials.gov, reference lists of articles
      and conference proceedings will be searched for relevant studies. No language or
      date restrictions will be applied. Eligible studies will include adults with CLD
      of any etiology. Included studies will be randomized controlled trials. From
      included studies, data on participant characteristics, study design, setting,
      research ethics compliance, and intervention outcomes will be extracted. Risk of
      bias in included studies will be assessed using the Cochrane Risk of Bias Tool. A
      random-effects meta-analysis will be conducted. If substantial or considerable
      levels of heterogeneity are detected, analysis will be limited to a narrative
      synthesis. DISCUSSION: This systematic review will examine the effectiveness of
      pharmacological therapies on fatigue reduction in people with CLD. Such therapies
      may be more effective than non-pharmacological interventions in treating fatigue
      symptoms in CLD. Evidence derived from the findings of this study will guide
      future practice, policy, and research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO,
      CRD42017076957.

PMID- 29444701
TI  - A case series on common cold to severe bronchiolitis and pneumonia in children
      following human metapneumovirus infection in Sri Lanka.
AB  - OBJECTIVES: The prevalence of hMPV infections in Sri Lanka has not been reported
      and here we report a case series of hMPV infection in children less than 5 years.
      Patients with ARTI were included from Teaching Hospital, Anuradhapura from March
      2013 to August 2014. Indirect fluorescence assay was performed on nasopharyngeal
      aspirates for the identification of respiratory viruses [respiratory syncytial
      virus (RSV), parainfluenza virus 1, 2 and 3, influenza A and B and hMPV].
      Moreover, reverse transcriptase-polymerase chain reaction was done to further
      confirm the hMPV infection. RESULTS: In this case series, hMPV infection showed a
      range of respiratory symptoms from common cold to life threatening lower
      respiratory tract infections with varying severity. In some cases, the clinical
      presentation of hMPV infection was similar to the ARTI caused by RSV. hMPV co
      infections with of RSV have also been seen in some cases of ARTI. A child
      delivered through cesarean section and birth order > 3 has an Odds ratio of 3.5
      and 4.3 (95% CI) for developing co-infection with RSV compared to hMPV mono
      infections. Lack of diagnostic facilities to identify the viral aetiology has
      contributed to the use of antibiotics indicating the need for establishing viral
      diagnostic facilities in the country.

PMID- 29444702
TI  - Correction to: Patients and surgeons provide endorsement of core domains for
      total joint replacement clinical trials.
AB  - CORRECTION: Unfortunately, after publication of this article [1], it was noticed
      that Table 2 was not correctly formatted during the production process. The
      corrected Table 2 can be seen below and the original article has been updated to
      match.

PMID- 29444703
TI  - Whole bone testing in small animals: systematic characterization of the
      mechanical properties of different rodent bones available for rat fracture
      models.
AB  - OBJECTIVES: Rat fracture models are extensively used to characterize normal and
      pathological bone healing. Despite, systematic research on inter- and intra
      individual differences of common rat bones examined is surprisingly not
      available. Thus, we studied the biomechanical behaviour and radiological
      characteristics of the humerus, the tibia and the femur of the male Wistar rat
      all of which are potentially available in the experimental situation-to identify
      useful or detrimental biomechanical properties of each bone and to facilitate
      sample size calculations. METHODS: 40 paired femura, tibiae and humeri of male
      Wistar rats (10-38 weeks, weight between 240 and 720 g) were analysed by DXA,
      pQCT scan and three-point-bending. Bearing and loading bars of the biomechanical
      setup were adapted percentually to the bone's length. Subgroups of light
      (skeletal immature) rats under 400 g (N = 11, 22 specimens of each bone) and
      heavy (mature) rats over 400 g (N = 9, 18 specimens of each bone) were formed and
      evaluated separately. RESULTS: Radiologically, neither significant differences
      between left and right bones, nor a specific side preference was evident. Mean
      side differences of the BMC were relatively small (1-3% measured by DXA and 2.5
      5% by pQCT). Over all, bone mineral content (BMC) assessed by DXA and pQCT (TOT
      CNT, CORT CNT) showed high correlations between each other (BMC vs. TOT and CORT
      CNT: R2 = 0.94-0.99). The load-displacement diagram showed a typical,
      reproducible curve for each type of bone. Tibiae were the longest bones (mean
      41.8 +/- 4.12 mm) followed by femurs (mean 38.9 +/- 4.12 mm) and humeri (mean
      29.88 +/- 3.33 mm). Failure loads and stiffness ranged from 175.4 +/- 45.23 N /
      315.6 +/- 63.00 N/mm for the femurs, 124.6 +/- 41.13 N / 260.5 +/- 59.97 N/mm for
      the humeri to 117.1 +/- 33.94 N / 143.8 +/- 36.99 N/mm for the tibiae. Smallest
      interindividual differences were observed in failure loads of the femurs (CV%
      8.6) and tibiae (CV% 10.7) of heavy animals, light animals showed good
      consistency in failure loads of the humeri (CV% 7.7). Most consistent results of
      both sides (left vs. right) in failure loads were provided by the femurs of light
      animals (mean difference 4.0 +/- 2.8%); concerning stiffness, humeri of heavy
      animals were most consistent (mean difference of 6.2 +/- 5%). In general, the
      failure loads showed strong correlations to the BMC (R2 = 0.85-0.88) whereas
      stiffness correlated only moderate, except for the humerus (BMC vs. stiffness: R2
      = 0.79). DISCUSSION: Altogether, the rat's femur of mature specimens showed the
      most accurate and consistent radiological and biomechanical results. In synopsis
      with the common experimental use enabling comparison among different studies,
      this bone offers ideal biomechanical conditions for three point bending
      experiments. This can be explained by the combination of a superior aspect ratio
      and a round and long, straight morphology, which satisfies the beam criteria more
      than other bones tested.

PMID- 29444704
TI  - hPMSC transplantation restoring ovarian function in premature ovarian failure
      mice is associated with change of Th17/Tc17 and Th17/Treg cell ratios through the
      PI3K/Akt signal pathway.
AB  - BACKGROUND: Human placenta-derived mesenchymal stem cell (hPMSC) transplantation
      has been demonstrated to be an effective way of recovering ovarian function in
      mice with autoimmune induced premature ovarian failure (POF). But the exact
      mechanism remains unclear. The goal of the present study is to investigate the
      role of immune factors (T-helper 17 (Th17), cytotoxic T (Tc17) and regulatory T
      (Treg) cells) in the recovery of ovarian function and whether the
      phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway is involved in the
      regulation. METHODS: The inhibitor of PI3K/Akt was administered to observe its
      effect on ovarian function recovery and immune regulation. Serum levels of
      estradiol (E2), follicle stimulation hormone (FSH), luteinizing hormone (LH) and
      anti-Mullerian hormone (AMH)) and anti-Zona pellucida antibody (AZPAb) were
      measured by ELISA to evaluate ovarian function. The morphological changes of
      ovaries were observed by HE staining. Apoptosis of granular cells (GCs) was
      determined by detecting the expression of capase-3. Expression of p-Akt protein
      was detected by immunohistochemistry and western blot assay in ovarian tissues.
      The MTT assay was performed to assess GC proliferation. GC apoptosis was
      performed using flow cytometry analysis. Percentages of Th17, Tc17 and Treg cells
      were detected by flow cytometry. Expression of interleukin (IL)-17 in serum was
      measured by ELISA. RESULTS: LY294002 administration decreased serum levels of E2
      and AMH, while the levels of FSH, LH and AZPAb in serum were increased compared
      with mice in the hPMSC transplantation group. The ovarian morphology presented as
      atrophy and fibrosis, with functional follicles exhausted. The expression of p
      Akt in ovarian tissue was significantly decreased. Also, LY294002 administration
      significantly decreased proliferation and increased cell apoptosis in GCs, and
      for immune factors the ratios of Th17/Tc17 and Th17/Treg cells were significantly
      increased, as well as the serum levels of IL-17. CONCLUSIONS: Our data suggest
      that the PI3K/Akt signal pathway is involved in the recovery of ovarian function
      by changing the ratios of Th17/ Tc17 and Th17/Treg cells in POF mice following
      hPMSC transplantation.

PMID- 29444705
TI  - Health economic evaluation of moist wound care in chronic cutaneous leishmaniasis
      ulcers in Afghanistan.
AB  - BACKGROUND: The present health economic evaluation in Afghanistan aims to support
      public health decision makers and health care managers to allocate resources
      efficiently to appropriate treatments for cutaneous leishmaniasis (CL) elicited
      by Leishmania tropica or Leishmania major. METHODS: A decision tree was used to
      analyse the cost and the effectiveness of two wound care regimens versus intra
      lesional antimony in CL patients in Afghanistan. Costs were collected from a
      societal perspective. Effectiveness was measured in wound free days. The
      incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit
      (NMB) were calculated. The model was parameterized with baseline parameters,
      sensitivity ranges, and parameter distributions. Finally, the model was simulated
      and results were evaluated with deterministic and probability sensitivity
      analyses. Final outcomes were the efficiency of the regimens and a budget impact
      analysis in the context of Afghanistan. RESULTS: Average costs per patients were
      US$ 11 (SE = 0.016) (Group I: Intra-dermal Sodium Stibogluconate [IL SSG]), US$
      16 (SE = 7.58) (Group II: Electro-thermo-debridement [ETD] + Moist wound
      treatment [MWT]) and US$ 25 (SE = 0.48) (Group III: MWT) in patients with a
      single chronic CL ulcer. From a societal perspective the budget impact analysis
      shows that the regimens' drug costs are lower than indirect disease cost. Average
      effectiveness in wound free days are 177 (SE = 0.36) in Group II, 147 (SE = 0.33)
      in Group III, and 129 (SE = 0.27) in Group I. The ICER of Group II versus Group I
      was US$ 0.09 and Group III versus Group I US$ 0.77, which is very cost-effective
      with a willingness-to-pay threshold of US$ 2 per wound free day. Within a Monte
      Carlo probabilistic sensitivity analysis Group II was cost-effective in 80% of
      the cases starting at a willingness-to-pay of 80 cent per wound free day.
      CONCLUSIONS: Group II provided the most cost-effective treatment. The non
      treatment alternative is not an option in the management of chronic CL ulcers.
      MWT of Group III should at least be practiced. The cost-effectiveness of Group
      III depends on the number of dressings necessary until complete wound closure.

PMID- 29444706
TI  - Bilateral Piriform sinus fistulas: a case study and review of management options.
AB  - BACKGROUND: Piriform sinus fistulas occur due to developmental abnormalities of
      the third and fourth branchial arches, and almost always occur unilaterally. They
      generally present as recurrent abscesses in the anterior-inferior neck, with
      concurrent thyroiditis. They have conventionally been managed with complete
      removal of the sinus tract, and thyroidectomy if required; however, endoscopic
      approaches have been increasingly favored. Herein we describe a case of bilateral
      piriform sinus fistulas, and present a review of the literature concerning their
      endoscopic management. CASE PRESENTATION: Our patient was determined to have
      bilateral piriform sinus fistulas based on computer tomography, magnetic
      resonance imaging and microlaryngoscopy. We performed electrocauterization of the
      proximal fistula tracts, followed by injection of fibrin sealent. Our patient has
      not had a recurrence in the ten months since his procedure. There were no
      complications. Twenty-three articles describing an endoscopic approach to these
      fistulas were identified through PubMed, and a search through the references of
      related articles was completed. CONCLUSION: Of one hundred and ninety-five
      patient cases we reviewed, an endoscopic procedure success rate of 82% and
      complication rate of 5.6% was determined. Piriform sinus fistulas that occur
      bilaterally are a rare congenital abnormality of the neck. Endoscopic approaches
      are an acceptable alternative option to open procedures, with similar success and
      a lower rate of complications.

PMID- 29444708
TI  - Rasch analysis of the Trypophobia Questionnaire.
AB  - OBJECTIVE: This study aimed to assess Rasch-based psychometric properties of the
      Trypophobia Questionnaire measuring proneness to trypophobia, which refers to
      disgust and unpleasantness induced by the observation of clusters of objects
      (e.g., lotus seed pods). RESULTS: Rasch analysis was performed on data from 582
      healthy Japanese adults. The results suggested that Trypophobia Questionnaire has
      a unidimensional structure with ordered response categories and sufficient person
      and item reliabilities, and that it does not have differential item functioning
      across sexes and age groups, whereas the targeting of the scale leaves room for
      improvements. When items that did not fit the Rasch model were removed, the
      shortened version showed slightly improved psychometric properties. However,
      results were not conclusive in determining whether the full or shortened version
      is better for practical use. Further assessment and validation are needed.

PMID- 29444707
TI  - Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for
      suspected malignant hilar obstruction: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: The optimal approach to the drainage of malignant obstruction at the
      liver hilum remains uncertain. We aim to compare percutaneous transhepatic
      biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the
      first intervention in patients with cholestasis due to suspected malignant hilar
      obstruction (MHO). METHODS: The INTERCPT trial is a multi-center, comparative
      effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of
      suspected MHO. One hundred and eighty-four eligible patients across medical
      centers in the United States, who provide informed consent, will be randomly
      assigned in 1:1 fashion via a web-based electronic randomization system to either
      ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All
      subsequent clinical interventions, including crossover to the alternative
      procedure, will be dictated by treating physicians per usual clinical care.
      Enrolled subjects will be assessed for successful biliary drainage (primary
      outcome measure), adequate tissue diagnosis, adverse events, the need for
      additional procedures, hospitalizations, and oncological outcomes over a 6-month
      follow-up period. Subjects, treating clinicians and outcome assessors will not be
      blinded. DISCUSSION: The INTERCPT trial is designed to determine whether PTBD or
      ERC is the better initial approach when managing a patient with suspected MHO, a
      common clinical dilemma that has never been investigated in a randomized trial.
      TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1
      June 2017.

PMID- 29444709
TI  - Mucinous cystic neoplasm of the liver with extrahepatic growth presenting with
      ascending cholangitis diagnosed by endoscopic ultrasound features: a case report.
AB  - BACKGROUND: Mucinous cystic neoplasm of the liver with extrahepatic growth is a
      rare benign epithelial neoplasm of the biliary system that presents with a mass
      effect or is incidentally found on imaging. The tumor affects mostly the common
      hepatic duct, which is difficult to diagnose preoperatively by radiology,
      endoscopy, or cystic fluid analysis. Endoscopic ultrasound is a noninvasive tool
      for the evaluation of features of a cystic lesion and the extent of disease.
      Optimal treatment is complete tumor resection. CASE PRESENTATION: A 27-year-old
      Thai woman was referred to our hospital for investigation and treatment of
      clinical symptoms of obstructive jaundice and ascending cholangitis, as well as
      an unknown cause of obstruction. Multiple investigations were performed,
      including endoscopic retrograde cholangiography and magnetic resonance imaging.
      Endoscopic ultrasound showed a multiloculated cystic lesion with internal
      septations without communication to the bile duct, which helped to support a
      diagnosis of mucinous cystic neoplasm. Eventually, the pathological diagnosis
      made was mucinous cystic neoplasm of the bile duct. A follow-up clinical
      examination with imaging at 6 months revealed that the patient was asymptomatic
      and without recurrence. CONCLUSIONS: We report a rare case of a patient with a
      large mucinous cystic neoplasm of the liver with extrahepatic growth causing
      biliary obstruction, which was diagnosed on the basis of endoscopic ultrasound
      features. Following definitive diagnosis, treatment with complete surgical
      resection using a multidisciplinary approach was successful.

PMID- 29444710
TI  - A novel in vitro model for the assessment of postnatal myonuclear accretion.
AB  - BACKGROUND: Due to the post-mitotic nature of myonuclei, postnatal myogenesis is
      essential for skeletal muscle growth, repair, and regeneration. This process is
      facilitated by satellite cells through proliferation, differentiation, and
      subsequent fusion with a pre-existing muscle fiber (i.e., myonuclear accretion).
      Current knowledge of myogenesis is primarily based on the in vitro formation of
      syncytia from myoblasts, which represents aspects of developmental myogenesis,
      but may incompletely portray postnatal myogenesis. Therefore, we aimed to develop
      an in vitro model that better reflects postnatal myogenesis, to study the cell
      intrinsic and extrinsic processes and signaling involved in the regulation of
      postnatal myogenesis. METHODS: Proliferating C2C12 myoblasts were trypsinized and
      co-cultured for 3 days with 5 days differentiated C2C12 myotubes. Postnatal
      myonuclear accretion was visually assessed by live cell time-lapse imaging and
      cell tracing by cell labeling with Vybrant(r) DiD and DiO. Furthermore, a
      Cre/LoxP-based cell system was developed to semi-quantitatively assess in vitro
      postnatal myonuclear accretion by the conditional expression of luciferase upon
      myoblast-myotube fusion. Luciferase activity was assessed luminometrically and
      corrected for total protein content. RESULTS: Live cell time-lapse imaging,
      staining-based cell tracing, and recombination-dependent luciferase activity,
      showed the occurrence of postnatal myonuclear accretion in vitro. Treatment of co
      cultures with the myogenic factor IGF-I (p < 0.001) and the cytokines IL-13 (p <
      0.05) and IL-4 (p < 0.001) increased postnatal myonuclear accretion, while the
      myogenic inhibitors cytochalasin D (p < 0.001), myostatin (p < 0.05), and
      TNFalpha (p < 0.001) decreased postnatal myonuclear accretion. Furthermore,
      postnatal myonuclear accretion was increased upon recovery from electrical pulse
      stimulation-induced fiber damage (p < 0.001) and LY29004-induced atrophy (p <
      0.001). Moreover, cell type-specific siRNA-mediated knockdown of myomaker in
      myoblasts (p < 0.001), but not in myotubes, decreased postnatal myonuclear
      accretion. CONCLUSIONS: We developed a physiologically relevant, sensitive, high
      throughput cell system for semi-quantitative assessment of in vitro postnatal
      myonuclear accretion, which can be used to mimic physiological myogenesis
      triggers, and can distinguish the cell type-specific roles of signals and
      responses in the regulation of postnatal myogenesis. As such, this method is
      suitable for both basal and translational research on the regulation of postnatal
      myogenesis, and will improve our understanding of muscle pathologies that result
      from impaired satellite cell number or function.

PMID- 29444711
TI  - Information needs in people with diabetes mellitus: a systematic review.
AB  - BACKGROUND: The purpose of this study was to identify and analyse currently
      available knowledge on information needs of people with diabetes mellitus, also
      considering possible differences between subgroups and associated factors.
      METHODS: Twelve databases including MEDLINE, EMBASE and the Cochrane Library were
      searched up until June 2015. Publications that addressed self-reported
      information needs of people with diabetes mellitus were included. Each study was
      assessed by using critical appraisal tools, e.g. from the UK National Institute
      for Health and Care Excellence. Extraction and content analysis were performed
      systematically. RESULTS: In total, 1993 publications were identified and 26 were
      finally included. Nine main categories of information needs were identified,
      including 'treatment-process', 'course of disease', 'abnormalities of glucose
      metabolism' and 'diabetes through the life cycle'. Differences between patient
      subgroups, such as type of diabetes or age, were sparsely analysed. Some studies
      analysed associations between information needs and factors such as participation
      preferences or information seeking. They found, for example, that information
      needs on social support or life tasks were associated with information seeking in
      Internet forums. CONCLUSION: Information needs in people with diabetes mellitus,
      appear to be high, yet poorly investigated. Research is needed regarding
      differences between diverse diabetes populations, including gender aspects or
      changes in information needs during the disease course. SYSTEMATIC REVIEW
      REGISTRATION: The review protocol has been registered at Prospero (
      CRD42015029610 ).

PMID- 29444712
TI  - Physical activity as treatment for alcohol use disorders (FitForChange): study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Help-seeking for alcohol use disorders (AUDs) is low and traditional
      treatments are often perceived as stigmatizing. Physical activity has positive
      effects on mental and physical health which could benefit this population. We
      propose to compare the effects of aerobic training, yoga, and usual care for AUDs
      in physically inactive Swedish adults. METHODS: This is a three-group, parallel,
      single-blind, randomized controlled trial (RCT). In total, 210 adults (aged 18-75
      years) diagnosed with an AUD will be invited to participate in a 12-week
      intervention. The primary study outcome is alcohol consumption measure by the
      Timeline Follow-back method and the Alcohol Use Disorders Identification Test
      (AUDIT). Secondary outcomes include: depression, anxiety, perceived stress, sleep
      quality, physical activity levels, fitness, self-efficacy, health-related quality
      of life, and cognition. Blood samples will be taken to objectively assess heavy
      drinking, and saliva to measure cortisol. Acute effects of exercise on the urge
      to drink alcohol, mood, and anxiety will also be assessed. DISCUSSION: The
      treatment potential for exercise in AUDs is substantial as many individuals with
      the disorder are physically inactive and have comorbid health problems. The study
      is the first to assess the effects of physical activity as a stand-alone
      treatment for AUDs. Considerable attention will be given to optimizing exercise
      adherence. Both the feasibility and treatment effects of exercise interventions
      in AUDs will be discussed. The Ethical Review Board (EPN) at Karolinska
      Institutet has approved the study (DNR: 2017/1380-3). TRIAL REGISTRATION: German
      Clinical Trials Register, ID: DRKS00012311. Registered on 26 September 2017.

PMID- 29444713
TI  - Evaluation of hospital outcomes: the relation between length-of-stay,
      readmission, and mortality in a large international administrative database.
AB  - BACKGROUND: Hospital mortality, readmission and length of stay (LOS) are commonly
      used measures for quality of care. We aimed to disentangle the correlations
      between these interrelated measures and propose a new way of combining them to
      evaluate the quality of hospital care. METHODS: We analyzed administrative data
      from the Global Comparators Project from 26 hospitals on patients discharged
      between 2007 and 2012. We correlated standardized and risk-adjusted hospital
      outcomes on mortality, readmission and long LOS. We constructed a composite
      measure with 5 levels, based on literature review and expert advice, from
      survival without readmission and normal LOS (best) to mortality (worst outcome).
      This composite measure was analyzed using ordinal regression, to obtain a
      standardized outcome measure to compare hospitals. RESULTS: Overall, we observed
      a 3.1% mortality rate, 7.8% readmission rate (in survivors) and 20.8% long LOS
      rate among 4,327,105 admissions. Mortality and LOS were correlated at the patient
      and the hospital level. A patient in the upper quartile LOS had higher odds of
      mortality (odds ratio = 1.45, 95% confidence interval 1.43-1.47) than those in
      the lowest quartile. Hospitals with a high standardized mortality had higher
      proportions of long LOS (r = 0.79, p < 0.01). Readmission rates did not correlate
      with either mortality or long LOS rates. The interquartile range of the
      standardized ordinal composite outcome was 74-117. The composite outcome had
      similar or better reliability in ranking hospitals than individual outcomes.
      CONCLUSIONS: Correlations between different outcome measures are complex and
      differ between hospital- and patient-level. The proposed composite measure
      combines three outcomes in an ordinal fashion for a more comprehensive and
      reliable view of hospital performance than its component indicators.

PMID- 29444714
TI  - Thiopurine S-methyltransferase activity in Nigerians: phenotypes and activity
      reference values.
AB  - OBJECTIVES: This study assessed the activity of thiopurine S-methyltransferase
      (TPMT) in Nigerians with a view to providing data on susceptibility to thiopurine
      toxicity, and as well generate reference activity values for clinical use.
      RESULTS: TPMT activity, expressed as the amount of 6MMP in ng/mL after 1 h
      incubation at 37  degrees C per haemoglobin (U/g Hb), varied between 2.34 and
      63.50 U/g Hb in the study population. Poor metabolic phenotypes, characterised by
      an activity values below 8.41 U/g Hb, were observed in 20% of the study subjects.
      Intermediate metabolizers had activity values between 8.41 and 16.13 U/g Hb. Fast
      and very fast metabolizers were characterised by activity values of 16.20-56.22
      and > 56.22 U/g Hb, respectively. These findings suggest that a potentially huge
      discordance between TPMT phenotype and genotype exist in Nigerians, and
      emphasizes the superiority of a prior determination of TPMT metabolic phenotype
      in ensuring the safety of thiopurine drug administration in the population.

PMID- 29444715
TI  - Porcine Wharton's jelly cells distribute throughout the body after
      intraperitoneal injection.
AB  - BACKGROUND: Wharton's jelly cells (WJCs) have multiple differentiation potentials
      and are easily harvested in large numbers. WJCs are well tolerated in allogeneic
      environments and there is a growing list of their therapeutic effects. Most
      therapies require administering large numbers of cells and this is generally
      accomplished by intravenous injection. Here, we studied the locations of porcine
      WJCs in immune-competent, allogeneic hosts after intraperitoneal (IP) injection.
      METHODS: Male porcine WJCs were administered to female neonatal piglets by IP
      injection. The location of transplanted cells was examined at 6 h, 24 h, and 7
      days after administration using confocal microscopy and polymerase chain reaction
      (PCR). Transplanted cells were also retrieved from the intestines of recipients
      and were cultured. Previously transplanted cells were identified by fluorescence
      in-situ hybridization (FISH) using a Y-chromosome probe. RESULTS: Allogeneic
      cells were identified in the small and large intestine, stomach, liver, spleen,
      diaphragm, omentum, kidney, pancreas, mesenteric lymph nodes, heart, lungs,
      uterus, bladder, and skeletal muscle. Male cells (SRY positive) were found in
      cultures of cells harvested from the intestinal mucosa 1 week after
      administration of male porcine WJCs. CONCLUSIONS: Our results show that porcine
      WJCs distribute widely to the organs in immunocompetent allogeneic hosts after IP
      administration. They may distribute through the lymphatics initially, and a
      prominent site of incorporation is the mucosa of the gastrointestinal tract. In
      that location they could function in the niche of endogenous stem cells and
      provide secretory products to cells in the tissue damaged by intestinal disease.

PMID- 29444716
TI  - Prevalence of inadequate micronutrient intakes of Canadian long-term care
      residents.
AB  - This study determines the prevalence of inadequate micronutrient intakes consumed
      by long-term care (LTC) residents. This cross-sectional study was completed in
      thirty-two LTC homes in four Canadian provinces. Weighed and estimated food and
      beverage intake were collected over 3 non-consecutive days from 632 randomly
      selected residents. Nutrient intakes were adjusted for intra-individual variation
      and compared with the Dietary Reference Intakes. Proportion of participants,
      stratified by sex and use of modified (MTF) or regular texture foods, with
      intakes below the Estimated Average Requirement (EAR) or Adequate Intake (AI),
      were identified. Numbers of participants that met these adequacy values with use
      of micronutrient supplements was determined. Mean age of males (n 197) was 85.2
      (sd 7.6) years and females (n 435) was 87.4 (sd 7.8) years. In all, 33 % consumed
      MTF; 78.2 % (males) and 76.1 % (females) took at least one micronutrient pill.
      Participants on a MTF had lower intake for some nutrients (males=4; females=8),
      but also consumed a few nutrients in larger amounts than regular texture
      consumers (males=4; females =1). More than 50 % of participants in both sexes and
      texture groups consumed inadequate amounts of folate, vitamins B6, Ca, Mg and Zn
      (males only), with >90 % consuming amounts below the EAR/AI for vitamin D, E, K,
      Mg (males only) and K. Vitamin D supplements resolved inadequate intakes for 50
      70 % of participants. High proportions of LTC residents have intakes for nine of
      twenty nutrients examined below the EAR or AI. Strategies to improve intake
      specific to these nutrients are needed.

PMID- 29444717
TI  - Good correlation between visual analogue scale and numerical rating scale in the
      assessment of nasal obstruction.
AB  - OBJECTIVE: Results from telephone interviews may be needed to supplement those
      from mailed questionnaires when response rates are inadequate. This study
      assessed the correlation between visual analogue scale ratings used in mailed
      questionnaires and numerical rating scale scores used in telephone interviews.
      METHODS: Patients scheduled for nasal septal surgery routinely respond to a
      visual analogue scale of obstruction during the day and at night. In this study,
      they were also asked to verbally rate their sense of obstruction using whole
      numbers. RESULTS: There was no significant difference between visual analogue
      scale and numerical rating scale obstruction scores. CONCLUSION: Ratings of nasal
      obstruction obtained with a numerical rating scale in telephone interviews are
      comparable to visual analogue scale scores in mailed questionnaires.

PMID- 29444718
TI  - Routine use of salivary bypass tubes in laryngectomy patients: systematic review.
AB  - BACKGROUND: Pharyngocutaneous fistula is a cause of significant morbidity
      following laryngectomy. Routine use of salivary bypass tubes during laryngectomy
      has been proposed to reduce the incidence of fistulae and neopharyngeal
      strictures. METHOD: Following a systematic search of Embase, Medline and Cochrane
      databases (1946 - current), included articles were assessed for bias according to
      the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Three
      case-control trials showed reduced pharyngocutaneous fistula rates with the use
      of salivary bypass tubes; six case series reported widely varied fistula rates.
      With regards to stricture rates, the largest case-control trial found no
      improvement with salivary bypass tube use. No fatal adverse events were observed
      among the 204 patients who received a salivary bypass tube. CONCLUSION: Low-level
      evidence suggests salivary bypass tubes may reduce the incidence of fistula in
      high-risk patient groups. A robust randomised controlled trial, or large,
      multicentre cohort studies, are needed to further examine this intervention.

PMID- 29444719
TI  - The significance of atherosclerosis in hypertensive patients with epistaxis.
AB  - BACKGROUND: The relationship between hypertension and epistaxis is controversial
      and poorly understood. The present research investigated atherosclerosis as a
      potential risk factor in hypertensive patients with epistaxis. METHODS: A
      prospective study of 141 hypertensive patients with epistaxis was conducted. The
      laboratory tests included full blood count, lipid profile and coagulation
      profile. All patients underwent funduscopic examination of the eye and were
      classified in terms of four retinopathy grades. RESULTS: There were strong
      positive correlations between the number of nosebleeds and retinopathy grade and
      low-density lipoprotein cholesterol level. There were weak correlations between
      the number of nosebleeds and blood pressure readings and triglycerides levels.
      Patients with grade III retinopathy, suggesting atherosclerosis, suffered from
      more frequent nosebleeds than other patients. CONCLUSION: Atherosclerosis is one
      of the potential risk factors in hypertensive patients with epistaxis. This may
      have an impact on treatment choices.

PMID- 29444720
TI  - MATERNAL SENSITIVITY AND PERFORMANCE AND VERBAL INTELLIGENCE IN LATE CHILDHOOD
      AND ADOLESCENCE.
AB  - The aim of this study was to investigate the association between maternal
      sensitivity and offspring intelligence in late childhood and adolescence.
      Secondary data (N=117) from the Block and Block (2006a, b) 30-year longitudinal
      study of Californian children, which began in the late 1960s, was used to test
      the hypothesis that maternal sensitivity in childhood would be predictive of late
      childhood and adolescent intelligence. Correlational analyses revealed that
      maternal sensitivity, as judged by raters viewing mother's interactions with
      their children in a set of four joint structured cognitive tasks when the child
      was 5 years of age, was associated with verbal and performance IQ test scores
      when the children were ages 11 and 18. Using hierarchical regression to control
      for child sex, socioeconomic status, child temperament, child baseline IQ (as
      measured at age 4), mother's level of education and mother's emotional
      nurturance, it was found that the maternal sensitivity and child and adolescent
      IQ association held for verbal, but not performance IQ. Furthermore, a pattern
      emerged in which the association between maternal sensitivity and verbal IQ was
      stronger for adolescents with a lower baseline IQ. The results suggest that
      maternal sensitivity is associated with offspring verbal intelligence and that
      this association holds when numerous variables are accounted for. Additionally,
      this association may be stronger for children with lower IQs.

PMID- 29444722
TI  - An event-semantic account of spatial modification in the acquisition of Mandarin.
AB  - This study investigates Mandarin-speaking children's knowledge of event semantics
      in interpreting spatial modifiers with zai 'at' after a posture verb or before a
      placement verb. The event-semantic principles investigated include subevent
      modification (Parsons, 1990) and aspect shift (Fong, 1997). We conducted an
      experimental study using modified forced choice, video choice, and elicited
      production techniques with five groups of children (two- to six-year-olds) and an
      adult control group. Three-year-olds were sensitive to the ambiguity of zai-PPs
      with placement verbs and posture verbs, suggesting guidance from principles of
      aspect shift and subevent modification. On the other hand, distributional
      properties of the input play a role in acquiring the interpretation and word
      order of zai: e.g., four-year-olds significantly differed from adults in
      accepting non-target V-zai sentences, as some verb classes can take postverbal
      prepositional phrases with zai while others cannot in adult usage.

PMID- 29444723
TI  - Evaluation of the Xpert MTB/RIF Performance on Tissues: Potential Impact on
      Airborne Infection Isolation at a Tertiary Cancer Care Center.
AB  - OBJECTIVES In this study, we sought to evaluate the performance of the Xpert
      MTB/RIF (Cepheid) assay for the detection of Mycobacterium tuberculosis (MTB)
      complex DNA on fresh and formalin-fixed, paraffin-embedded (FFPE) tissue
      specimens from oncology patients in an area with a low prevalence of
      tuberculosis. We also aimed to retrospectively assess the potential impact of
      Xpert MTB/RIF on the duration of airborne infection isolation (AII). SETTING A
      473-bed, tertiary-care cancer center in New York City. DESIGN A total of 203
      tissue samples (101 FFPE and 102 fresh) were tested using Xpert MTB/RIF,
      including 133 pulmonary tissue samples (65.5%) and 70 extrapulmonary tissue
      samples (34.5%). Acid-fast bacilli (AFB) culture was used as the diagnostic gold
      standard. The limit of detection (LOD) and reproducibility were also evaluated
      for both samples types using contrived specimens. The potential impact of the
      Xpert MTB PCR assay on tissue samples from AII patients on AII duration was
      retrospectively assessed. RESULTS Using the Xpert MTB/RIF for fresh tissue
      specimens, the sensitivity was 50% (95% CI, 1.3%-98.7%) and the specificity was
      99% (95% CI, 94.5%-99.9%). For FFPE tissue specimens, the sensitivity was 100%
      (95% CI, 63.1%-100%) and the specificity was 98.3% (95% CI, 95.5%-100%. The LOD
      was 103 colony-forming units (CFU)/mL for both fresh and FFPE tissue specimens,
      and the Xpert MTB/RIF was 100% reproducible at concentrations 10 times that of
      the LOD. With an expected turnaround time of 24 hours, the Xpert MTB PCR could
      decrease the duration of AII from a median of 8 days to a median of 1 day.
      CONCLUSIONS The Xpert MTB/RIF assay offers a valid option for ruling out
      Mycobacterium tuberculosis complex (MTBC) on tissue samples from oncology
      patients and for minimizing AII resource utilization. Infect Control Hosp
      Epidemiol 2018;39:462-466.

PMID- 29444721
TI  - Psychological treatments delivered by community health workers in low-resource
      government health systems: effectiveness of group interpersonal psychotherapy for
      caregivers of children affected by nodding syndrome in Uganda.
AB  - BACKGROUND: Despite increasing evidence for the benefits of psychological
      treatments (PTs) in low- and middle-income countries, few national health systems
      have adopted PTs as standard care. We aimed to evaluate the effectiveness of a
      group interpersonal psychotherapy (IPT-G) intervention, when delivered by lay
      community health workers (LCHWs) in a low-resource government health system in
      Uganda. The intended outcome was reduction of depression among caregivers of
      children with nodding syndrome, a neuropsychiatric condition with high morbidity,
      mortality and social stigma. METHODS: A non-randomized trial design was used.
      Caregivers in six villages (n = 69) received treatment as usual (TAU), according
      to government guidelines. Caregivers in seven villages (n = 73) received TAU as
      well as 12 sessions of IPT-G delivered by LCHWs. Primary outcomes were caregiver
      and child depression assessed at 1 and 6 months post-intervention. RESULTS:
      Caregivers who received IPT-G had a significantly greater reduction in the risk
      of depression from baseline to 1 month [risk ratio (RR) 0.25, 95% confidence
      interval (CI) 0.10-0.62] and 6 months (RR 0.33, 95% CI 0.11-0.95) post
      intervention compared with caregivers who received TAU. Children of caregivers
      who received IPT-G had significantly greater reduction in depression scores than
      children of TAU caregivers at 1 month (Cohen's d = 0.57, p = 0.01) and 6 months
      (Cohen's d = 0.54, p = 0.03). Significant effects were also observed for
      psychological distress, stigma and social support among caregivers. CONCLUSION:
      IPT-G delivered within a low-resource health system is an effective PT for common
      mental health problems in caregivers of children with a severe neuropsychiatric
      condition and has psychological benefits for the children as well. This supports
      national health policy initiatives to integrate PTs into primary health care
      services in Uganda.

PMID- 29444724
TI  - Early postoperative remodelling following repair of tetralogy of Fallot utilising
      unsedated cardiac magnetic resonance: a pilot study.
AB  - : IntroductionThe right ventricular adaptations early after surgery in infants
      with tetralogy of Fallot are important to understand the changes that occur later
      on in life; this physiology has not been fully delineated. We sought to assess
      early postoperative right ventricular remodelling in patients with tetralogy of
      Fallot by cardiac MRI.Materials and methodSubjects with tetralogy of Fallot under
      1 year of age were recruited following complete surgical repair for tetralogy of
      Fallot. Protocol-based cardiac MRI to assess anatomy, function, and flows was
      performed before hospital discharge using the feed and sleep technique, an
      unsedated imaging technique. RESULTS: MRI was completed in 16 subjects at a
      median age of 77 days (interquartile range 114). There was normal ventricular
      ejection fraction and indexed right ventricular end-diastolic volume (48+/-13
      cc/m2), but elevated right ventricular mass (z score 6.2+/-2.4). Subjects
      requiring a transannular patch or right ventricle to pulmonary artery conduit had
      moderate pulmonary insufficiency (regurgitant fraction 27+/-16%).DiscussionEarly
      right ventricular remodelling after surgical repair for tetralogy of Fallot is
      characterised by significant pulmonary regurgitation, right ventricular
      hypertrophy, and lack of dilation. Performing cardiac MRI using the feed and
      sleep technique is feasible in infants younger than 5 months. These results might
      open new avenues to study longitudinal right ventricular changes in tetralogy of
      Fallot and to further explore the utility of unsedated MRI in patients with other
      types of CHDs.

PMID- 29444725
TI  - Potential Impact of Antibiotic Stewardship Programs on Overall Antibiotic Use in
      Adult Acute-Care Hospitals in the United States.

PMID- 29444726
TI  - Resting-state thalamic dysconnectivity in schizophrenia and relationships with
      symptoms.
AB  - BACKGROUND: Schizophrenia (SZ) is a severe neuropsychiatric disorder associated
      with disrupted connectivity within the thalamic-cortico-cerebellar network.
      Resting-state functional connectivity studies have reported thalamic
      hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic
      hyperconnectivity with sensory cortical regions in SZ patients compared with
      healthy comparison participants (HCs). However, fundamental questions remain
      regarding the clinical significance of these connectivity abnormalities. METHOD:
      Resting state seed-based functional connectivity was used to investigate thalamus
      to whole brain connectivity using multi-site data including 183 SZ patients and
      178 matched HCs. Statistical significance was based on a voxel-level FWE
      corrected height threshold of p < 0.001. The relationships between positive and
      negative symptoms of SZ and regions of the brain demonstrating group differences
      in thalamic connectivity were examined. RESULTS: HC and SZ participants both
      demonstrated widespread positive connectivity between the thalamus and cortical
      regions. Compared with HCs, SZ patients had reduced thalamic connectivity with
      bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had
      greater thalamic connectivity with multiple sensory-motor regions, including
      bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and
      middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity
      was positively correlated with hallucinations and delusions, while thalamus to
      cerebellar connectivity was negatively correlated with delusions and bizarre
      behavior. CONCLUSIONS: Thalamic hyperconnectivity with sensory regions and
      hypoconnectivity with cerebellar regions in combination with their relationship
      to clinical features of SZ suggest that thalamic dysconnectivity may be a core
      neurobiological feature of SZ that underpins positive symptoms.

PMID- 29444727
TI  - New Zealand breakfast cereals: are there sufficient low-sugar, low-sodium
      options?

PMID- 29444728
TI  - The Long-Term Effects of the Deepwater Horizon Oil Spill on Women's Depression
      and Mental Distress.
AB  - OBJECTIVE: The purpose of the study is to describe changes in mental health among
      women following an oil spill and to examine their association with the Deepwater
      Horizon oil spill (DHOS). METHODS: The Women and Their Children's Health study
      followed 2038 women in Louisiana after the DHOS. Subjects were interviewed in
      2012-2014 and 2014-2016. Oil spill exposure was characterized using survey items
      about economic and physical exposures. Outcomes were depressive symptoms and
      mental distress. RESULTS: After adjustment for relevant demographics, depressive
      symptoms increased over 2 time points following the DHOS, whereas symptoms of
      mental distress decreased. For every year increase in time since the DHOS, the
      rate ratio for depressive symptoms increased by a factor of 1.08. In contrast,
      the rate ratio for mental distress decreased by a factor of 0.97. In addition,
      initial associations between economic and physical exposure to the DHOS persisted
      up to 6 years after the spill; women who were more highly exposed experienced
      higher levels of depressive symptoms (rate ratios ranged from 1.08 to 1.11) and
      mental distress (rate ratios from 1.05 to 1.11) at each time point than women who
      were less exposed. CONCLUSION: A better understanding of recovery patterns
      following an oil spill can help direct critical mental health response efforts.
      (Disaster Med Public Health Preparedness. 2018;page 1 of 8).

PMID- 29444729
TI  - Gemella bergeri infective endocarditis: a case report and brief review of
      literature.
AB  - Gemella is a genus of Gram-positive bacteria found in the digestive tract of
      humans. They rarely cause systemic illness but have been recently implicated in
      several serious infections. We report infective endocarditis caused by Gemella
      bergeri in a 23-year-old with a bicuspid aortic valve status post-intervention in
      infancy.

PMID- 29444730
TI  - Outbreak of ST395 KPC-Producing Klebsiella pneumoniae in a Neonatal Intensive
      Care Unit in Palermo, Italy.

PMID- 29444731
TI  - Isolated aortic dilation without osteoarthritis: a case of SMAD3 mutation.
AB  - Aneurysm-osteoarthritis syndrome is a recently discovered inherited autosomal
      dominant connective tissue disease caused by SMAD3 mutations. Aneurysm
      osteoarthritis syndrome is responsible for 2% of familial thoracic aortic
      aneurysms and dissections and is characterised by aneurysms, dissections, and
      tortuosity throughout the arterial tree in combination with osteoarthritis. Early
      onset osteoarthritis is present in almost all patients. We present the case of a
      non-syndromic young boy with SMAD3 mutation isolated from the dilated aortic root
      and ascending aorta without osteoarthritis.

PMID- 29444732
TI  - Can Gasping be Used as a Tool to Determine Whether to Perform Compression-Only
      CPR versus Conventional CPR?
AB  - Rottenberg EM . Can gasping be used as a tool to determine whether to perform
      compression-only CPR versus conventional CPR? Prehosp Disaster Med.
      2018;33(2):225-226.

PMID- 29444733
TI  - Medically Attended Catheter Complications Are Common in Patients With Outpatient
      Central Venous Catheters.
AB  - OBJECTIVE Outpatient central venous catheters (CVCs) are being used more
      frequently; however, data describing mechanical complications and central-line
      associated bloodstream infections (CLABSI) in the outpatient setting are limited.
      We performed a retrospective observational cohort study to understand the burden
      of these complications to elucidate their impact on the healthcare system.
      METHODS Data were retrospectively collected on patients discharged from
      Vanderbilt University Medical Center with a CVC in place and admitted into the
      care of Vanderbilt Home Care Services. Risk factors for medically attended
      catheter-associated complications (CACs) and outpatient CLABSIs were analyzed.
      RESULTS A CAC developed in 143 patients (21.9%), for a total of 165 discrete CAC
      events. Among these, 76 (46%) required at least 1 visit to the emergency
      department or an inpatient admission, while the remaining 89 (54%) required an
      outpatient clinic visit. The risk for developing a CAC was significantly
      increased in female patients, patients with a CVC with >1 lumen, and patients
      receiving total parenteral nutrition. The absolute number of CLABSIs identified
      in the study population was small at 16, or 2.4% of the total cohort. CONCLUSIONS
      Medically attended catheter complications were common among outpatients
      discharged with a CVC, and reduction of these events should be the focus of
      outpatient quality improvement programs. Infect Control Hosp Epidemiol
      2018;39:439-444.

PMID- 29444734
TI  - Growth performance, carcass and noncarcass traits and meat quality of Barbarine
      lambs fed rosemary distillation residues.
AB  - The aim of this experiment was to study the effect of total replacement of oat
      hay by rosemary distillation residues (RR) on growth, carcass characteristics and
      meat quality of Barbarine lambs. A total of 21 lambs were divided into three
      groups. The control group (C) was offered 600 g of oat hay; the RR87 and RR60
      groups received 600 g of pellets containing 87% and 60% of RR, respectively. The
      CP content was 9% and 14% for RR87 and RR60, respectively. All animals were
      supplemented by 600 g of concentrate. After 77 days of fattening, lambs were
      slaughtered. The DM and CP intakes were significantly increased with RR diets.
      The average daily gain was higher (P<0.001), while the feed conversion rate was
      lower for RR60 and RR87 than C group. The dressing percentage was similar for all
      groups. The tissular (muscle, fat and bone) and the regional (leg, shoulder,
      etc.) carcass composition did not differ among groups. The bony organs and gut
      weights were similar among groups, while functional ones (skin, liver, kidney and
      testicles) were significantly heavier for both RR groups than control. The
      ultimate pH, water cooking loss and color variables were similar among groups and
      the chemical composition (protein, fat, myoglobin, collagen and iron) did not
      differ also among groups. These results revealed the opportunity of RR use in
      fattening lambs without adverse effects on carcass and meat characteristics.
      Moreover, 9% CP in RR pellets are enough given the same growth performance
      recorded as that of RR with 14% CP.

PMID- 29444735
TI  - Short Assessment of Health Literacy (SAHL) in Portugal: development and
      validation of a self-administered tool.
AB  - The goal of this study was to adapt, improve and validate a short, self
      administered health literacy assessment tool for European Portuguese-speaking
      adults. Health literacy tools are of great importance to health authorities and
      professionals, as low or inadequate health literacy, that is, a limited capacity
      to handle health-related information, is associated with higher morbidity and
      mortality. The 18-item Short Assessment of Health Literacy for Brazilian
      Portuguese-speaking adults (SAHLPA-18) was adapted into European Portuguese. The
      European Portuguese tool (SAHLPA-23) includes five additional items. The SAHLPA
      23 was tested in a convenience sample of 503 participants from two Portuguese
      regions. Socio-demographic data, literacy and cognitive indicators were
      collected. Participants also completed a questionnaire on comprehension of
      written health materials. Construct validity was assessed through correlations
      between SAHLPA-23 scores and education, literacy, and cognitive variables and
      score on the comprehension questionnaire. The psychometric properties of the new
      tool were compared with those of the SAHLPA-18. The mean SAHLPA-18 and SAHLPA-23
      scores were 13.9 (77.2%; SD=2.9) and 18.3 (79.6%; SD=3.8), respectively. Both
      tools showed adequate reliability (Cronbach's alpha>0.7). SAHLPA-23 was more
      highly correlated with all study variables than SAHLPA-18. Although both
      instruments displayed acceptable discriminative power, SAHLPA-23 had better
      accuracy than SAHLPA-18 (DeLong's method: DeltaAUC=0.09, Z=3.36; P<0.001). The
      SAHLPA-23 is an independent, feasible and innovative tool for estimation of
      health literacy in the Portuguese adult population.

PMID- 29444736
TI  - Recognition of the complexity facing residential care homes: a practitioner
      inquiry.
AB  - : Aim To explore the experiences and challenges for residential care home staff
      when managing the healthcare needs of their residents, in particular those living
      with dementia. BACKGROUND: Increasing number of older people, with complex health
      and social care needs are living in residential care homes. Yet there is limited
      appreciation of why staff sometimes struggle to manage residents' healthcare
      needs, or understanding of their working relationship with district nurses (DNs),
      whose responsibility it is to provide nursing support. METHODS: This PhD study,
      in a metropolitan area in the United Kingdom, was conducted by an experienced DN
      and involved three phases. This paper focuses on the first two phases. Phase 1
      data included: semi-structured interviews (n=8), reflective field notes based on
      non-participant observation, documentary analysis of policies, procedures and
      assessment tools and other contextual data from one care home (case study site).
      The practitioner researcher reflected on the findings from the case study, in
      relation to her own knowledge and experience as a DN, focusing in particular on
      findings that were familiar, or which surprised. In Phase 2 she fed these
      findings back to other care homes (n=11) to check whether the findings from the
      single case study were unique or resonated with others. She gathered their
      feedback through semi-structured interviews with senior care staff (n=14). Data
      were analysed using thematic data analysis. Findings Findings highlight the
      complexity facing residential care homes: high levels of healthcare needs amongst
      residents, the demands of caring for residents living with dementia, variations
      in the knowledge and skill set of care staff, inequity in the level of healthcare
      support, the challenges of building a good relationship with DNs, and funding
      pressures facing care homes. Implications Any, or all of these factors can
      prevent care home staff from managing the healthcare needs of their residents.

PMID- 29444737
TI  - Offspring birth weight and cardiovascular mortality among parents: the role of
      cardiovascular risk factors.
AB  - An inverse association between offspring birth weight (BW) and higher risk of
      parental cardiovascular disease (CVD) mortality and morbidity has been reported.
      Shared environmental, genetic and intrauterine factors may be responsible for
      explaining these associations. We studied the role of parental CVD risk factors
      in the association between offspring BW and CVD mortality among mothers and
      fathers. All births registered in Medical Birth Registry Norway (1967-2012) were
      linked to three health surveys, National Educational Registry and Cause of Death
      Registry. Number of births with information of parental CVD risk factors
      available for the analyses was 1,006,557 (520,670 for mothers and 485,887 for
      fathers). Cox proportional hazards regression models were used, following CVD
      deaths in parents from 1974 to 2012. An inverse association between offspring BW
      and CVD mortality was observed among both parents: hazard ratio 1.60 (1.44-1.75)
      for mothers and 1.16 (1.10-1.23) for fathers. Among mothers, adjustment for
      smoking, triglycerides and diabetes reduced the risk to 1.36 (1.25-1.52), 1.57
      (1.43-1.73) and 1.58 (1.43-1.79), respectively. Adjustment for diastolic blood
      pressure (DBP) and systolic blood pressure (SBP) both reduced the risk to 1.53
      (1.37-1.66). Among fathers, adjustments for smoking, DBP, SBP reduced the risk to
      1.08 (1.02-1.15), 1.13 (1.06-1.19) and 1.14 (1.08-1.22), respectively.
      Triglycerides and diabetes both reduced the risk to 1.15 (1.09-1.12). Our results
      indicate that shared environmental factors might be important in the association.
      A stronger association in mothers suggest that intrauterine factors also are at
      play.

PMID- 29444738
TI  - The Influence of Traffic, Area Location, and Other Factors on Operating Room
      Microbial Load.
AB  - OBJECTIVE To determine how the movement of patients, equipment, materials, staff,
      and door openings within the operating room (OR) affect microbial loads at
      various locations within the OR. DESIGN Observation and sampling study. SETTING
      Academic health center, public hospital. METHODS We first analyzed 27 videotaped
      procedures to determine the areas in the OR with high and low numbers of people
      in transit. We then placed air samplers and settle plates in representative
      locations during 21 procedures in 4 different ORs during 2 different seasons of
      the year to measure microbial load in colony-forming units (CFU). The temperature
      and humidity, number of door openings, physical movement, and the number of
      people in the OR were measured for each procedure. Statistical analysis was
      conducted using hierarchical regression. RESULTS The microbial load was affected
      by the time of year that the samples were taken. Both microbial load measured by
      the air samplers and by settle plates in 1 area of the OR was correlated with the
      physical movement of people in the same area but not with the number of door
      openings and the number of people in the OR. CONCLUSIONS Movement in the OR is
      correlated with the microbial load. Establishing operational guidelines or
      developing OR layouts that focus on minimizing movement by incorporating
      desirable internal storage points and workstations can potentially reduce
      microbial load, thereby potentially reducing surgical site infection risk. Infect
      Control Hosp Epidemiol 2018;39:391-397.

PMID- 29444739
TI  - Ultra-processed food product brands on Facebook pages: highly accessed by
      Brazilians through their marketing techniques.
AB  - OBJECTIVE: To analyse the content and extent of marketing of ultra-processed food
      products (UPP) and their brand pages on Facebook, which are highly accessed by
      Brazilians. DESIGN: Descriptive. SETTING: Sixteen UPP brand pages on Facebook
      were selected from 250 pages that were the most liked by Brazilians in October
      2015. SUBJECTS: We analysed the frequency of 'likes' and members 'talking about'
      each one of the pages, in addition to fifteen marketing techniques used in the
      previous year (September 2014 to October 2015). The number of posts, likes,
      'shares' and 'commentaries', and the mean number of likes, shares and
      commentaries per post, were collected for one month, from 23 September to 23
      October 2015. RESULTS: The two most liked pages were: Coke(r) (93 673 979 likes)
      and McDonald's(r) (59 749 819 likes). Regarding the number of people talking
      about the pages, McDonald's led with 555 891 commentaries, followed by Coke (287
      274), Burger King(r) (246 148) and Kibon(r) (244 523). All pages used marketing
      techniques, which included photos, user conversations, presence of brand elements
      and links. Videos were observed on 93.8 % of the pages; promotions on 68.8 %; and
      celebrities on 62.5 %. In one month, Garoto(r), Outback(r) and Coke were brands
      that published more than one post per day. Kibon achieved the highest ratio of
      likes per post (285 845.50) and Burger King had the highest mean shares per post
      (10 083.93), including commentaries per post (7958.13). CONCLUSIONS: UPP
      marketing is extensively used on Facebook pages and is highly accessed by
      Brazilians, with UPP companies employing a diversity of marketing strategies.

PMID- 29444740
TI  - Associations between modifiable lifestyle factors and multidimensional cognitive
      health among community-dwelling old adults: stratified by educational level.
AB  - : ABSTRACTBackground:Cognition is multidimensional, and each domain plays a
      unique and crucial part in successful daily life engagement. However, less
      attention has been paid to multi-domain cognitive health for the elderly, and the
      role of lifestyle factors in each domain remains unclear. METHODS: We conducted a
      cross-sectional study of 3,230 older adults aged 60+ years in Xiamen, China, in
      2016. The Montreal Cognitive Assessment (MoCA) was used to measure general
      cognition and six specific sub-domains. To account for educational effects, we
      adjusted the MoCA score and divided respondents into three education-specific
      groups (low, moderate, and high education groups with <=5, 6~8, and >=9 years of
      education, respectively). A series of proportional odds models were used to
      detect the associations between two categories of lifestyle factors - substance
      abuse (cigarette and alcohol) and leisure activity (TV watching, reading,
      smartphone use, social activity, and exercise) - and general cognition and the
      six sub-domains in those three groups. RESULTS: Among the 3,230 respondents,
      2,617 eligible participants were included with a mean age of 69.05 +/- 7.07
      years. Previous or current smoking/drinking was not associated with MoCA scores
      in the whole population, but unexpectedly, the ex-smokers in the low education
      group performed better in general cognition (OR = 2.22) and attention (OR = 2.05)
      than their never-smoking counterparts. Modest TV watching, reading, and
      smartphone use also contributed to better cognition among elderly participants in
      the low education group. For the highly educated elderly, comparatively longer
      reading (>3.5 hours/week) was inversely associated with general cognition (OR =
      0.53), memory (OR = 0.59), and language (OR = 0.54), while adequate exercise (5~7
      days/week) was positively related to these factors with OR = 1.48, OR = 1.49, and
      OR = 1.53, respectively. For the moderately educated elderly, only modest reading
      was significantly beneficial. CONCLUSIONS: Lifestyle factors play different roles
      in multidimensional cognitive health in different educational groups, indicating
      that individual intervention strategies should be designed according to specific
      educational groups and different cognitive sub-domains.

PMID- 29444741
TI  - Assessment measures in palliative care: The risk of inflation and the importance
      of listening to the patient's story.

PMID- 29444742
TI  - Effects of Disaster Damage and Working Conditions on Mental Health Among Public
      Servants 16 Months After the Great East Japan Earthquake.
AB  - OBJECTIVE: To explore whether stressors after a disaster have later effects on
      the mental health of public servants who engage in disaster response and to
      estimate the proportion of those experiencing persistent mental distress.
      METHODS: We analyzed the data of health surveys conducted in Miyagi Prefecture
      for all prefectural public servants at 2, 7, and 16 months after the Great East
      Japan Earthquake (n=3174). We investigated relationships between mental distress
      (defined as K6>=10) at 16 months after the earthquake and earthquake damage and
      working conditions at 2 months. We also calculated the proportion of participants
      who scored K6>=10 on all 3 surveys. RESULTS: The experience of living someplace
      other than one's own home was significantly related with mental distress at 16
      months after the earthquake. Few participants consistently scored K6>=10
      throughout all 3 surveys. CONCLUSIONS: The effects of stressors in the aftermath
      of a disaster could remain for a long time. Few public servants experienced
      persistent mental distress. Disaster Med Public Health Preparedness. 2018;12:622
      630.

PMID- 29444743
TI  - Tumor suppressive microRNA-708 targets Notch1 to suppress cell proliferation and
      invasion in gastric cancer.
AB  - Growing evidence demonstrated that numerous microRNAs (miRNAs) may participate in
      the regulation of gastric carcinogenesis and progression. This phenomenon
      suggests that gastric cancer-related miRNAs can be identified as effective
      therapeutic targets for this disease. MiRNA-708 (miR-708) has recently been
      reported to be aberrantly expressed in several types of cancer and contribute to
      carcinogenesis and progression. However, the expression level, biological roles
      and underlying mechanisms of miR-708 in gastric cancer are poorly understood.
      Here, we found that miR-708 was down-regulated in gastric cancer tissues and cell
      lines. Down-regulated miR-708 expression was significantly associated with
      lymphatic metastasis, invasive depth and TNM stage. Further investigation
      indicated that ectopic expression of miR-708 prohibited cell proliferation and
      invasion in gastric cancer. Bioinformatics analysis showed that Notch1 was a
      potential target of miR-708. Notch1 was further confirmed as a direct target gene
      of miR-708 in gastric cancer by luciferase reporter assay, reverse
      transcriptionquantitative polymerase chain reaction and Western blot analysis.
      Furthermore, an inverse association was found between miR-708 and Notch1 mRNA
      level in gastric cancer tissues. In addition, restored Notch1 expression rescued
      the inhibitory effects on gastric cancer cell proliferation and invasion induced
      by miR-708 overexpression. Our findings highlight the tumor suppressive roles of
      miR-708 in gastric cancer and suggest that miR708 may be investigated as a novel
      target for gastric cancer treatment.

PMID- 29444744
TI  - Overexpression of Pyruvate dehydrogenase E1a subunit Inhibits Warburg effect and
      Induces Cell Apoptosis through Mitochondria-mediated Pathway in Hepatocellular
      Carcinoma.
AB  - Most cancers rely disproportionately on glycolysis for energy even in the
      presence of adequate oxygen supply, a condition known as "aerobic glycolysis", or
      the "Warburg effect". Pyruvate dehydrogenase E1a subunit (PDHA1) is one of main
      factors for metabolic switch from oxidative phosphorylation (OXPHOS) to aerobic
      glycolysis and has been suggested to be closely associated with tumorigenesis.
      Here we observed that PDHA1 protein was reduced in hepatocellular carcinoma (HCC)
      specimens by immunohistochemistry and western blot, which was significantly
      associated with poor overall survival. To further analyze the function of PDHA1
      in cancer cells, it was up-regulated in HCC cell line SMMC-7721 and HepG2. The
      results demonstrated that overexpression of PDHA1 gene inhibited aerobic
      glycolysis with lower lactate via increased PDH activity, meanwhile mitochondrial
      OXPHOS was enhanced accompanied with higher ATP and lower glucose consumption. We
      also found that apoptosis was promoted and intrinsic pathway proteins was
      increased in PDHA1 overexpressing cells. Collectively, our data indicate that
      reduced PDHA1 protein expression is associated with poor clinical outcome HCC
      cancers. Up-regulated PDHA1 gene expression can inhibit Warburg effect and
      enhanced mitochondria-mediated apoptosis pathway.

PMID- 29444745
TI  - MicroRNA-598 Inhibits Cell Proliferation and Invasion of Glioblastoma by Directly
      Targeting Metastasis Associated in Colon Cancer-1 (MACC1).
AB  - The dysregulation of microRNA (miRNA) expression is closely related with
      tumorigenesis and tumor development in glioblastoma (GBM). In this study, we
      found that miRNA-598 (miR-598) expression was significantly downregulated in GBM
      tissues and cell lines. Restoring miR-598 expression inhibited cell proliferation
      and invasion in GBM. Moreover, we validated that metastasis associated in colon
      cancer-1 (MACC1) is a novel target of miR-598 in GBM. Restoring MACC1 expression
      reversed the inhibitory effects of miR-598 overexpression on GBM cells. In
      addition, miR-598 overexpression suppressed Met/AKT pathway activation in GBM.
      Our results provided compelling evidence that miR-598 serves tumor-suppressive
      roles in GBM and that its antioncogenic effects are mediated chiefly through the
      direct suppression of MACC1 expression and regulation of the Met/AKT signaling
      pathway. Therefore, miR-598 is a potential target in the treatment of GBM.

PMID- 29444746
TI  - Using marijuana, drinking alcohol or a combination of both: the association of
      marijuana, alcohol and sexual risk behaviour among adolescents.
AB  - : Background Although the association between alcohol use and sexual risk
      behaviour has been well-documented, there is little understanding of whether
      marijuana use alone or combining marijuana with alcohol use contributes to sexual
      risk behaviour among adolescents. METHODS: A diverse sample of sexually active
      adolescents (n = 616) aged 12-18 years (50.32% Hispanic; 31.17% Black) completed
      a survey on alcohol use, marijuana use and sexual risk behaviour during a visit
      to a primary care clinic. RESULTS: Adolescents were more likely to report having
      had two or more sexual partners in the past 3 months if they reported using both
      alcohol and marijuana (OR=3.90, P<0.0001), alcohol alone (OR=2.51, P<0.0001) or
      marijuana alone (OR=1.89, P<0.001) compared with adolescents who reported no use
      during the past month. Adolescents were more likely to report having both two or
      more partners and condomless sex if they used both alcohol and marijuana
      (OR=3.19, P<0.001) or alcohol alone (OR=3.41, P<0.01) in the past month compared
      with adolescents who reported using marijuana alone or had no use of either.
      CONCLUSIONS: Providers should screen for both alcohol and marijuana use among
      adolescents and discuss how use of alcohol or alcohol in conjunction with
      marijuana may be associated with sexual risk behaviours.

PMID- 29444747
TI  - HIV susceptibility among clients of female sex workers in Indonesia: a
      qualitative inquiry.
AB  - : Background The spread of HIV infection among men in Indonesia continues to
      increase every year. Clients of female sex workers (FSWs) are a group at higher
      risk of acquiring HIV infection due to their frequent engagement in sexual acts
      with sex workers. This study aimed to identify factors of susceptibility to HIV
      infection among clients of FSWs. METHODS: A qualitative inquiry using one-on-one
      in-depth interviews was conducted in the Belu and Malaka districts of Indonesia
      from January to April 2017. The study participants (n =42) were the clients of
      FSWs recruited using the snowball sampling technique. The inclusion criteria
      were: being a client of FSWs and being aged 18 years or more. Data were analysed
      using a framework analysis. RESULTS: Findings were grouped into two main emerging
      themes that included behavioural and socioeconomic factors. Behavioural factors
      that mediated HIV susceptibility among clients of FSWs were: frequent engagement
      in unsafe sex with multiple sex workers; low perceptions of the relevance of
      available HIV and AIDS services and limited access to these services; and HIV
      stigma or fear of being labelled as HIV positive. Socioeconomic factors included:
      participants' economic situation; and individuals' household responsibility and
      ability to afford FSWs services. CONCLUSIONS: The study results indicate the need
      to reformulate and improve HIV and AIDS-related services, including increasing
      the level of availability of HIV service points and the dissemination of
      knowledge and information about HIV and AIDS and condom use and making them
      accessible to both FSWs and their clients in Belu and Malaka districts.

PMID- 29444748
TI  - Aortopulmonary collaterals in neonates with d-transposition of the great arteries
      - Clinical significance early after arterial switch operation.
AB  - OBJECTIVES: Purpose of this study is to evaluate the clinical significance of
      major aortopulmonary collateral arteries (MAPCAs) during the early postoperative
      course after arterial switch operation (ASO) in d-transposition of the great
      arteries (dTGA). METHODS: Clinical data of 98 patients with simple dTGA between
      January 2007 and December 2016 at the University Children's Hospital Zurich,
      Switzerland were analyzed retrospectively. RESULTS: 37 from 98 patients (38%)
      required cardiac catheterization (CC) due to an early complicated postoperative
      course or difficult coronary transfer due to special coronary anatomy. In 15
      (15%) patients, hemodynamically relevant MAPCAs were found during CC and coil
      embolization was performed. Patients with relevant MAPCAs had a significantly
      longer PICU stay (7 versus 6 days, p = 0.021), longer hospital stay (41 versus 27
      days, p = 0.005), longer mechanical ventilation time (5 versus 3 days, p =
      0.005), longer need for inotropic support (5 versus 4 days, p = 0.001) and
      delayed chest closure time (3 versus 2 days, p = 0.030) in those in whom it was
      left open in comparison to all other patients. In patients having CC, pre-surgery
      oxygen saturation was significantly lower in patients with relevant MAPCAs (58%
      vs 70%, p 0.019). Echocardiography had a sensitivity of 53% and a specificity of
      100% in detecting relevant MAPCAs, accurately. CONCLUSIONS: MAPCAs are frequently
      found in dTGA patients and can be associated with lower baseline oxygen
      saturation and a prolonged postoperative course after ASO. Transthoracic
      echocardiography cannot replace CC as diagnostic tool. If significant MAPCAs are
      suspected, early CC should be performed for diagnostic and therapeutic reasons.

PMID- 29444749
TI  - Microbiological diagnosis of adult tuberculous meningitis in a ten-year cohort in
      Indonesia.
AB  - We evaluated microbiological diagnosis of tuberculous (TB) meningitis in a
      referral hospital in Indonesia. Over a ten-year period, we examined cerebrospinal
      fluid (CSF) samples of 1180 adult meningitis suspects. Sensitivity of different
      methods was compared, and results were stratified for HIV status, disease
      severity, and CSF volume. TB meningitis was bacteriologically confirmed in 501
      patients. Using clinical diagnosis as reference standard (n = 713), sensitivity
      of different methods was 12.2% (86/703) for microscopy, 42% (73/174) for Xpert
      MTB/RIF, 46.0% (163/354) for solid culture, 48.8% (332/680) for liquid culture,
      and 64.0% (212/331) for in-house PCR. Head to head comparisons in 654 patients
      showed a higher yield of in-house PCR (32.3%) compared to culture (15.6%, P <
      0.01). Microscopic observation of drug susceptibility (MODS) culture more rapidly
      became positive compared to other culture methods. Yield of culture was lower in
      HIV-infected (39/105) than in HIV-negative patients (N = 316/585; P < 0.01).
      Molecular and culture methods gave higher yields in patients with more severe
      disease (P < 0.01). CSF volume of >=6 ml increased the yield of culture (42.8%
      versus 12.1% for CSF <6 ml, P < 0.01) and ZN-microscopy (18.3% versus 1.9% for
      CSF <6 ml, P < 0.01). CSF centrifugation had no clear effect on sensitivity of
      Xpert MTB/RIF. ZN-microscopy lacks sensitivity for diagnosis of TB meningitis.
      For molecular assays, in-house IS6110-PCR is more sensitive than Xpert MTB/RIF.
      MODS culture has a clear advantage in terms of speed. Large CSF volumes are
      necessary for all tests. The effect of CSF processing for Xpert MTB/RIF needs
      further study.

PMID- 29444750
TI  - Structures and properties of porphyrin-based film materials part I. The films
      obtained via vapor-assisted methods.
AB  - This review is devoted to porphyrin-based film materials. Various technological
      and scientific applications of ones are close to surface and interface related
      phenomena. In the part I of review the following topics are discussed the recent
      progress in field of submonolayers, monolayers and multilayers films on the vapor
      solid interfaces, including results on (i) conformational behavior of adsorbed
      molecules, (ii) aggregation and surface phases formation, (iii) on-surface
      coordination networks, and (iv) on-surface chemical reactions. The examples of
      combined approaches to developing materials and porphyrin-based film materials
      application are also presented.

PMID- 29444751
TI  - Management of dyspepsia-The role of the ED Observation unit to optimize patient
      outcomes.
AB  - BACKGROUND: Dyspepsia is a common complaint that can confer significant burden on
      one's quality of life and may also be associated with serious underlying
      conditions. The objective of this study was to determine if patients admitted to
      the emergency department observation unit (EDOU) for severe or persistent
      dyspepsia would have cost effective management in terms of investigations
      performed, length and cost of hospital stay. The secondary objective was to
      determine if any patient characteristics could predict a need for admission to
      the inpatient unit. METHODS: Retrospective chart reviews of patients admitted to
      the EDOU under the Dyspepsia protocol between January 2008 and August 2014 were
      conducted. Baseline demographics, investigations performed, outcomes related to
      EDOU stay, admission and 30-day re-presentation outcomes were recorded. RESULTS:
      A total of 1304 patients were included. Median length of stay was 1day.
      Cumulative bed-saved days were 38 per month. Two hundred eighteen (16.7%)
      patients required admission to the inpatient service for further management,
      while 533 (40.9%) and 313 (24.0%) patients underwent esophagogastroduodenoscopy
      and hepatobiliary ultrasonography, respectively. No major adverse events were
      attributed to the EDOU admissions or delays in treatment. No significant
      clinically relevant factors were associated with a need for admission from the
      EDOU to the inpatient unit. Median cost of the EDOU admission was approximately
      one-third that of a similar admission to the inpatient unit. CONCLUSION: The EDOU
      is an appropriate setting to facilitate investigations and treatment of patients
      with dyspepsia with considerable bed-saved days.

PMID- 29444752
TI  - A review of international pharmacy-based minor ailment services and proposed
      service design model.
AB  - BACKGROUND: The need to consider sustainable healthcare solutions is essential.
      An innovative strategy used to promote minor ailment care is the utilisation of
      community pharmacists to deliver minor ailment services (MASs). Promoting higher
      levels of self-care can potentially reduce the strain on existing resources. AIM:
      To explore the features of international MASs, including their similarities and
      differences, and consider the essential elements to design a MAS model. METHODS:
      A grey literature search strategy was completed in June 2017 to comply with the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses standard. This
      included (1) Google/Yahoo! search engines, (2) targeted websites, and (3) contact
      with commissioning organisations. Executive summaries, table of contents and
      title pages of documents were reviewed. Key characteristics of MASs were
      extracted and a MAS model was developed. RESULTS: A total of 147 publications
      were included in the review. Key service elements identified included
      eligibility, accessibility, staff involvement, reimbursement systems. Several
      factors need to be considered when designing a MAS model; including
      contextualisation of MAS to the market. Stakeholder engagement, service planning,
      governance, implementation and review have emerged as key aspects involved with a
      design model. CONCLUSION: MASs differ in their structural parameters.
      Consideration of these parameters is necessary when devising MAS aims and
      assessing outcomes to promote sustainability and success of the service.

PMID- 29444753
TI  - Liposome mediated double-stranded RNA delivery to silence ribosomal protein P0 in
      the tick Rhipicephalus haemaphysaloides.
AB  - Control of ticks has been achieved primarily by the application of acaricides,
      which has drawbacks such as environmental contamination leading to the selection
      of pesticide-resistant ticks. The potential of dsRNA to suppress genes critical
      for tick survival due to its sequence specificity suggests that dsRNAs could be
      developed as tailor-made pesticides. In this study, the dsRNA of P0 gene from the
      tick, Rhipicephalus haemaphysaloides, was evaluated as a potential anti-tick
      agent. Effects of using different dsRNA delivery methods were tested by
      quantitative RT-PCR and tick bioassays to determine survival, feeding and
      reproduction. The results showed that P0 dsRNAs could be effectively delivered
      into ticks and silenced by incubating with liposomes. Incubation time was found
      to be the most important factor in dsRNA delivery and gene silencing compared
      with liposome types and dsRNA concentration. The effects of P0 dsRNA treatment on
      ticks were found to be significant on blood feeding, molting or reproduction.
      These data show that anti-tick agents based on dsRNAs could have potential use in
      tick control.

PMID- 29444754
TI  - Clinical rating systems in elbow research-a systematic review exploring trends
      and distributions of use.
AB  - BACKGROUND: Clinical rating systems are used as outcome measures in clinical
      trials and attempt to gauge the patient's view of his or her own health. The
      choice of clinical rating system should be supported by its performance against
      established quality standards. METHODS: A search strategy was developed to
      identify all studies that reported the use of clinical rating systems in the
      elbow literature. The strategy was run from inception in Medline Embase and
      CINHAL. Data extraction identified the date of publication, country of data
      collection, pathology assessed, and the outcome measure used. RESULTS: We
      identified 980 studies that reported clinical rating system use. Seventy-two
      separate rating systems were identified. Forty-one percent of studies used >=2
      separate measures. Overall, 54% of studies used the Mayo Elbow Performance Score
      (MEPS). For arthroplasty, 82% used MEPS, 17% used Disabilities of Arm, Shoulder
      and Hand (DASH), and 7% used QuickDASH. For trauma, 66.7% used MEPS, 32% used
      DASH, and 23% used the Morrey Score. For tendinopathy, 31% used DASH, 23% used
      Patient-Rated Tennis Elbow Evaluation (PRTEE), and 13% used MEPS. Over time,
      there was an increased proportional use of the MEPS, DASH, QuickDASH, PRTEE, and
      the Oxford Elbow Score. CONCLUSIONS: This study identified a wide choice and
      usage of clinical rating systems in the elbow literature. Numerous studies
      reported measures without a history of either a specific pathology or cross
      cultural validation. Interpretability and comparison of outcomes is dependent on
      the unification of outcome measure choice. This was not demonstrated currently.

PMID- 29444755
TI  - Preventing infection in shoulder surgery.
AB  - Although rare, infection after shoulder surgery can represent a devastating
      complication. Infection can negatively affect clinical outcomes, and eradication
      often requires a protracted treatment course. Staphylococcus aureus,
      Staphylococcus epidermidis, and Cutibacterium acnes are among the most frequently
      isolated pathogens. Perioperative measures can be implemented to reduce infection
      risk. Here we review various perioperative practices and their efficacy at
      reducing infection after shoulder surgery.

PMID- 29444756
TI  - Local recurrence on PET/CT with 11C-choline following brachytherapy for prostate
      cancer: tracer uptake pattern.

PMID- 29444757
TI  - A review on the applications of microbial electrolysis cells in anaerobic
      digestion.
AB  - Anaerobic digestion (AD) has been widely used for biogas or biofuel generation
      from waste treatment. Because a low production rate and instability of AD occur
      frequently, various technologies have been applied to improvement of AD.
      Microbial electrolysis cells (MECs), an emerging technology, can convert organic
      matter into hydrogen, methane, and other value-added products. Recent studies
      showed that application of MEC to AD (MEC-AD) can accelerate degradation of a
      substrate (including recalcitrant compounds) and alter AD microbial community by
      enriching exoelectrogens and methanogens thus increasing biogas production. With
      stable microbial communities established, improvement of MEC-AD for methane
      production was achieved. MEC-AD process can be monitored in real-time by
      detecting electric signals, which linearly correlate with substrate
      concentrations. This review attempts to evaluate interactions among the
      decomposition of substrates, MEC-AD system, and the microbial community. This
      analysis should provide useful insights into the improvement of methane
      production and the performance of MEC-AD.

PMID- 29444758
TI  - Electron transfer process in microbial electrochemical technologies: The role of
      cell-surface exposed conductive proteins.
AB  - Electroactive microorganisms have attracted significant interest for the
      development of novel biotechnological systems of low ecological footprint. These
      can be used for the sustainable production of energy, bioremediation of metal
      contaminated environments and production of added-value products. Currently,
      almost 100 microorganisms from the Bacterial and Archaeal domains are considered
      electroactive, given their ability to efficiently interact with electrodes in
      microbial electrochemical technologies. Cell-surface exposed conductive proteins
      are key players in the electron transfer between cells and electrodes.
      Interestingly, it seems that among the electroactive organisms identified so far,
      these cell-surface proteins fall into one of four groups. In this review, the
      different types of cell-surface conductive proteins found in electroactive
      organisms will be overviewed, focusing on their structural and functional
      properties.

PMID- 29444759
TI  - Current management of pelvic organ prolapse in aging women: EMAS clinical guide.
AB  - Management of pelvic organ prolapse (POP) is a common and challenging task.
      Nowadays older women are more active than they were in the past, and the
      development of POP disrupts quality of life and impairs social and personal
      activities. The menopausal transition is a time of vulnerability, during which
      many women start experiencing symptoms and signs of POP. The role of hormonal
      changes or of hormonal therapies in influencing the development or progression of
      POP has been explored extensively. The management of POP requires considerable
      clinical skills. Correct diagnosis and characterization of the prolapse and an
      identification of the individual woman's most bothersome symptoms are the
      hallmark of appropriate initial management. Therapy is multimodal and often
      multidisciplinary, and requires a competence in pelvic medicine and surgery. The
      integration of hormonal, non-hormonal and surgical strategies is important and
      needs to be adjusted to changing circumstances on an individualized basis. When
      surgery is required, optimal management requires clinicians who are familiar with
      the advantages and disadvantages of all the available strategies and who are able
      to use these strategies in a tailored manner. Complex cases should be sent to
      specialist referral centers. Management of POP should be integrated into the
      practice of healthcare professionals dealing in menopause.

PMID- 29444760
TI  - Risk factors for persistent Aspergillus respiratory isolation in cystic fibrosis.
AB  - BACKGROUND: Aspergillus species are increasingly detected in the respiratory
      tracts of individuals with cystic fibrosis (CF), and chronic Aspergillus
      fumigatus is associated with more frequent hospitalizations for pulmonary
      exacerbations. However, patient and clinical factors that may contribute to the
      acquisition of persistent Aspergillus infection have yet to be identified. The
      objective of this study was to identify risk factors for development of
      Aspergillus respiratory isolation in CF. METHODS: A retrospective cohort study of
      participants in the CF Foundation Patient Registry between 2006 and 2012 was
      conducted. Generalized estimating equation models were used to evaluate the
      association between the development of persistent Aspergillus respiratory
      isolation and individual level demographic and clinical characteristics. RESULTS:
      Among 16,095 individuals with CF followed from 2006 to 2012, 1541 (9.6%) subjects
      developed persistent Aspergillus isolation. White race (Odds Ratio [OR] 1.74, 95%
      confidence interval 1.23, 2.48, p<0.001) and pancreatic insufficiency (OR 1.50,
      95% CI 1.09, 2.06, p<0.001) were found to be risk factors for persistent
      Aspergillus isolation. Chronic therapies, including inhaled antibiotics (OR 1.33;
      95% CI 1.21, 1.46), macrolides (OR 1.23, 95% CI 1.14, 1.32, p<0.001), and inhaled
      corticosteroids (OR 1.13, 95% CI 1.04, 1.20, p<0.001) were also independently
      associated with an increased risk for persistent Aspergillus isolation.
      CONCLUSIONS: We identified macrolides and inhaled antibiotics, which individually
      have been shown to improve CF outcomes, and inhaled corticosteroids as risk
      factors for developing persistent Aspergillus isolation. Further work is needed
      to determine whether these associations are causal or due to confounding by other
      factors.

PMID- 29444761
TI  - Chronic infection sustained by a Pseudomonas aeruginosa High-Risk clone producing
      the VIM-1 metallo-beta-lactamase in a cystic fibrosis patient after lung
      transplantation.
AB  - BACKGROUND: The significance of chronic lung infection by multidrug-resistant
      (MDR) pathogens in Cystic Fibrosis (CF) transplanted patients remains
      controversial, and the available information is overall limited. Here we describe
      the case of a chronic infection, sustained by a metallo-beta-lactamase (MBL)
      producing P. aeruginosa strain, in a CF patient following lung transplantation.
      METHODS: Twelve P. aeruginosa isolates collected from a CF patient over a 15
      years follow-up period after lung transplantation were analysed for their
      antibiotic susceptibility profile, MBL production and clonal relatedness.
      Available clinical and microbiological records were reviewed. RESULTS: The
      transplanted CF patient was chronically infected by an MBL-producing P.
      aeruginosa strain which harboured a blaVIM-1 determinant inserted into a novel
      class 1 integron. The strain exhibited an MDR phenotype and belonged to the
      globally widespread ST235 epidemic clonal lineage, which however is not a typical
      CF-associated epidemic clone. Despite the chronic infection, the long-term
      outcome of this patient during the post-transplant period was characterized by
      the absence of acute exacerbations and by a mostly stable pulmonary function.
      CONCLUSIONS: This report provides one of the few descriptions of MBL-producing P.
      aeruginosa infections in CF patients, and the first description of such an
      infection after lung transplantation in these patients. Infection with the MBL
      producing strain apparently did not significantly affect the patient pulmonary
      function.

PMID- 29444762
TI  - Hemimegalencephaly with Bannayan-Riley-Ruvalcaba syndrome.
AB  - Hemimegalencephaly is known to occur in Proteus syndrome, but has not been
      reported, to our knowledge, in the other PTEN mutation-related syndrome of
      Bannayan-Riley-Ruvalcaba. Here, we report a patient with Bannayan-Riley-Ruvalcaba
      syndrome who also had hemimegalencephaly and in whom the hemimegalencephaly was
      evident well before presentation of the characteristic manifestations of Bannayan
      Riley-Ruvalcaba syndrome. An 11-year-old boy developed drug-resistant focal
      seizures on the fifth day of life. MRI revealed left hemimegalencephaly. He later
      showed macrocephaly, developmental delay, athetotic quadriplegic cerebral palsy,
      and neuromuscular scoliosis. Freckling of the penis, which is characteristic of
      Bannayan-Riley-Ruvalcaba syndrome, was not present at birth but was observed at 9
      years of age. Gene analysis revealed a c.510 T>G PTEN mutation. This patient and
      his other affected family members, his father and two siblings, were started on
      the tumour screening procedures recommended for patients with PTEN mutations.
      This case highlights the importance of early screening for PTEN mutations in
      cases of hemimegalencephaly not otherwise explained by another disorder, even in
      the absence of signs of Proteus syndrome or the full manifestations of Bannayan
      Riley Ruvalcaba syndrome.

PMID- 29444763
TI  - Somatosensory reflex epilepsy: simultaneous video-EEG monitoring and surface EMG.
AB  - Somatosensory reflex epilepsy is induced by repetitive cutaneous contact of a
      circumscribed body area with a tight time-lock between somatosensory stimulation
      and seizure. We describe the case of a 27-year-old man with seizures induced by
      repetitive tapping on the sole of the right foot. Simultaneous video-EEG
      monitoring and surface electromyography was performed during a seizure triggered
      by repetitive tapping on the right sole aspect using a hammer. Stimulation
      produced a tingling sensation on the right sole that extended to the right lower
      leg. This was followed by motor Jacksonian march of the right leg. [Published
      with video sequence on www.epilepticdisorders.com].

PMID- 29444764
TI  - Clinical-radiological-pathological correlation in an unusual case of refractory
      epilepsy: a two-year journey of whodunit!
AB  - New-onset refractory focal epilepsy poses significant challenges to the clinician
      in the absence of specific diagnostic biomarkers. Differential diagnoses based on
      imaging may be expanded by a veritable spectrum of peri-ictal imaging findings
      that may mask the underlying substrate. We report a 13-year-old girl who
      presented with refractory focal seizures of left parieto-occipital origin with
      cytotoxic gyral oedema noted over the same region on imaging. Despite an initial
      negative autoantibody profile, the patient was treated with immunosuppression,
      followed by serial relapses requiring immune-modulation. Over the next year, her
      syndrome persisted as focal left posterior cortex epilepsy that necessitated
      occipital lobectomy, following a relapsing-remitting radiological profile,
      consistent with peri-ictal MRI changes. Histopathology was inconclusive for any
      definitive substrate. After a period of quiescence, she developed focal motor
      seizures of right hemispheric origin with progressive encephalopathy, at which
      point a repeat cerebrospinal fluid anti-N-methyl-D-aspartate receptor antibody
      profile returned positive. The patient was managed with steroids and rituximab
      with a good clinical outcome. We hypothesise that persistent or relapsing
      remitting focal gyral oedema in unexplained refractory focal epilepsy mandates
      consideration of focal encephalitis secondary to autoimmunity, and late
      appearance of intrathecal auto-antibody synthesis correlates with evolution into
      a more diffuse disease.

PMID- 29444765
TI  - Early infancy-onset stimulation-induced myoclonic seizures in three siblings with
      inherited glycosylphosphatidylinositol (GPI) anchor deficiency.
AB  - Inherited glycosylphosphatidylinositol anchor deficiency causes a variety of
      clinical symptoms, including epilepsy, however, little information is available
      regarding seizures as a symptom. We report three siblings with inherited
      glycosylphosphatidylinositol anchor deficiency with PIGL gene mutations. The
      phenotypes of the subjects were not consistent with CHIME syndrome or Mabry
      syndrome, as reported in previous studies. All shared some clinical
      manifestations, including transient apnoea as neonates, dysmorphic facial
      features, and intellectual disability. Between one week and 3 months of life, all
      patients developed myoclonic seizures. Myoclonic jerks were easily evoked by
      sudden unexpected acoustic or tactile stimuli. None showed elevation of serum
      alkaline phosphatase. Vitamin B6 was given to one of the three siblings, but
      failed to suppress seizures. The presence of early infancy-onset stimulation
      induced myoclonic seizures combined with dysmorphic facial features should lead
      physicians to consider the possibility of inherited glycosylphosphatidylinositol
      anchor deficiency.

PMID- 29444766
TI  - Know Your Epidemic, Strengthen Your Response: Developing a New HIV Surveillance
      Architecture to Guide HIV Resource Allocation and Target Decisions.
AB  - To guide HIV prevention and treatment activities up to 2020, we need to generate
      and make better use of high quality HIV surveillance data. To highlight our
      surveillance needs, a special collection of papers in JMIR Public Health and
      Surveillance has been released under the title "Improving Global and National
      Responses to the HIV Epidemic Through High Quality HIV Surveillance Data." We
      provide a summary of these papers and highlight methods for developing a new HIV
      surveillance architecture.

PMID- 29444767
TI  - Patient-Reported Measures for Person-Centered Coordinated Care: A Comparative
      Domain Map and Web-Based Compendium for Supporting Policy Development and
      Implementation.
AB  - BACKGROUND: Patient-reported measure (PRM) questionnaires were originally used in
      research to measure outcomes of intervention studies. They have now evolved into
      a diverse family of tools measuring a range of constructs including quality of
      life and experiences of care. Current health and social care policy increasingly
      advocates their use for embedding the patient voice into service redesign through
      new models of care such as person-centered coordinated care (P3C). If chosen
      carefully and used efficiently, these tools can help improve care delivery
      through a variety of novel ways, including system-level feedback for health care
      management and commissioning. Support and guidance on how to use these tools
      would be critical to achieve these goals. OBJECTIVE: The objective of this study
      was to develop evidence-based guidance and support for the use of P3C-PRMs in
      health and social care policy through identification of PRMs that can be used to
      enhance the development of P3C, mapping P3C-PRMs against an existing model of
      domains of P3C, and integration and organization of the information in a user
      friendly Web-based database. METHODS: A pragmatic approach was used for the
      systematic identification of candidate P3C-PRMs, which aimed at balancing
      comprehensiveness and feasibility. This utilized a number of resources, including
      existing compendiums, peer-reviewed and gray literature (using a flexible search
      strategy), and stakeholder engagement (which included guidance for relevant
      clinical areas). A subset of those candidate measures (meeting prespecified
      eligibility criteria) was then mapped against a theoretical model of P3C,
      facilitating classification of the construct being measured and the subsequent
      generation of shortlists for generic P3C measures, specific aspects of P3C (eg,
      communication or decision making), and condition-specific measures (eg, diabetes,
      cancer) in priority areas, as highlighted by stakeholders. RESULTS: In total, 328
      P3C-PRMs were identified, which were used to populate a freely available Web
      based database. Of these, 63 P3C-PRMs met the eligibility criteria for
      shortlisting and were classified according to their measurement constructs and
      mapped against the theoretical P3C model. We identified tools with the best
      coverage of P3C, thereby providing evidence of their content validity as outcome
      measures for new models of care. Transitions and medications were 2 areas
      currently poorly covered by existing measures. All the information is currently
      available at a user-friendly web-based portal (p3c.org.uk), which includes all
      relevant information on each measure, such as the constructs targeted and links
      to relevant literature, in addition to shortlists according to relevant
      constructs. CONCLUSIONS: A detailed compendium of P3C-PRMs has been developed
      using a pragmatic systematic approach supported by stakeholder engagement. Our
      user-friendly suite of tools is designed to act as a portal to the world of PRMs
      for P3C, and have utility for a broad audience, including (but not limited to)
      health care commissioners, managers, and researchers.

PMID- 29444768
TI  - Web-Based Just-in-Time Information and Feedback on Antibiotic Use for Village
      Doctors in Rural Anhui, China: Randomized Controlled Trial.
AB  - BACKGROUND: Excessive use of antibiotics is very common worldwide, especially in
      rural China; various measures that have been used in curbing the problem have
      shown only marginal effects. OBJECTIVE: The objective of this study was to test
      an innovative intervention that provided just-in-time information and feedback
      (JITIF) to village doctors on care of common infectious diseases. METHODS: The
      information component of JITIF consisted of a set of theory or evidence-based
      ingredients, including operation guideline, public commitment, and takeaway
      information, whereas the feedback component tells each participating doctor about
      his or her performance scores and percentages of antibiotic prescriptions. These
      ingredients were incorporated together in a synergetic way via a Web-based aid.
      Evaluation of JITIF adopted a randomized controlled trial design involving 24
      village clinics randomized into equal control and intervention arms. Measures
      used included changes between baseline and endpoint (1 year after baseline) in
      terms of: percentages of patients with symptomatic respiratory or
      gastrointestinal tract infections (RTIs or GTIs) being prescribed antibiotics,
      delivery of essential service procedures, and patients' beliefs and knowledge
      about antibiotics and infection prevention. Two researchers worked as a group in
      collecting the data at each site clinic. One performed nonparticipative
      observation of the service process, while the other performed structured exit
      interviews about patients' beliefs and knowledge. Data analysis comprised mainly
      of: (1) descriptive estimations of beliefs or knowledge, practice of indicative
      procedures, and use of antibiotics at baseline and endpoint for intervention and
      control groups and (2) chi-square tests for the differences between these groups.
      RESULTS: A total of 1048 patients completed the evaluation, including 532 at
      baseline (intervention=269, control=263) and 516 at endpoint (intervention=262,
      control=254). Patients diagnosed with RTIs and GTIs accounted for 76.5% (407/532)
      and 23.5% (125/352), respectively, at baseline and 80.8% (417/532) and 19.2%
      (99/532) at endpoint. JITIF resulted in substantial improvement in delivery of
      essential service procedures (2.6%-24.8% at baseline on both arms and at endpoint
      on the control arm vs 88.5%-95.0% at endpoint on the intervention arm, P<.001),
      beliefs favoring rational antibiotics use (11.5%-39.8% at baseline on both arms
      and at endpoint on the control arm vs 19.8%-62.6% at endpoint on the intervention
      arm, P<.001) and knowledge about side effects of antibiotics (35.7% on the
      control arm vs 73.7% on the intervention arm, P<.001), measures for managing or
      preventing RTIs (39.1% vs 66.7%, P=.02), and measures for managing or preventing
      GTIs (46.8% vs 69.2%, P<.001). It also reduced antibiotics prescription (from
      88.8%-62.3%, P<.001), and this decrease was consistent for RTIs (87.1% vs 64.3%,
      P<.001) and GTIs (94.7% vs 52.4%, P<.001). CONCLUSIONS: JITIF is effective in
      controlling antibiotics prescription at least in the short term and may provide a
      low-cost and sustainable solution to the widespread excessive use of antibiotics
      in rural China.

PMID- 29444769
TI  - Effectiveness of a Web-Based Self-Help Program for Suicidal Thinking in an
      Australian Community Sample: Randomized Controlled Trial.
AB  - BACKGROUND: Treatment for suicidality can be delivered online, but evidence for
      its effectiveness is needed. OBJECTIVE: The goal of our study was to examine the
      effectiveness of an online self-help intervention for suicidal thinking compared
      to an attention-matched control program. METHODS: A 2-arm randomized controlled
      trial was conducted with assessment at postintervention, 6, and, 12 months.
      Through media and community advertizing, 418 suicidal adults were recruited to an
      online portal and were delivered the intervention program (Living with Deadly
      Thoughts) or a control program (Living Well). The primary outcome was severity of
      suicidal thinking, assessed using the Columbia Suicide Severity Rating Scale.
      RESULTS: Intention-to-treat analyses showed significant reductions in the
      severity of suicidal thinking at postintervention, 6, and 12 months. However, no
      overall group differences were found. CONCLUSIONS: Living with Deadly Thoughts
      was of no greater effectiveness than the control group. Further investigation
      into the conditions under which this program may be beneficial is now needed.
      Limitations of this trial include it being underpowered given the effect size
      ultimately observed, a high attrition rate, and the inability of determining
      suicide deaths or of verifying self-reported suicide attempts. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12613000410752; https://www.anzctr.org.au/
      Trial/Registration/TrialReview.aspx?id=364016 (Archived by WebCite at
      http://www.webcitation.org/6vK5FvQXy); Universal Trial Number U1111-1141-6595.

PMID- 29444770
TI  - Randomised trials are not the only evidence, and for some questions they may not
      be the best.

PMID- 29444772
TI  - Ultra-processed foods and cancer.

PMID- 29444771
TI  - Consumption of ultra-processed foods and cancer risk: results from NutriNet-Sante
      prospective cohort.
AB  - OBJECTIVE: To assess the prospective associations between consumption of ultra
      processed food and risk of cancer. DESIGN: Population based cohort study. SETTING
      AND PARTICIPANTS: 104 980 participants aged at least 18 years (median age 42.8
      years) from the French NutriNet-Sante cohort (2009-17). Dietary intakes were
      collected using repeated 24 hour dietary records, designed to register
      participants' usual consumption for 3300 different food items. These were
      categorised according to their degree of processing by the NOVA classification.
      MAIN OUTCOME MEASURES: Associations between ultra-processed food intake and risk
      of overall, breast, prostate, and colorectal cancer assessed by multivariable Cox
      proportional hazard models adjusted for known risk factors. RESULTS: Ultra
      processed food intake was associated with higher overall cancer risk (n=2228
      cases; hazard ratio for a 10% increment in the proportion of ultra-processed food
      in the diet 1.12 (95% confidence interval 1.06 to 1.18); P for trend<0.001) and
      breast cancer risk (n=739 cases; hazard ratio 1.11 (1.02 to 1.22); P for
      trend=0.02). These results remained statistically significant after adjustment
      for several markers of the nutritional quality of the diet (lipid, sodium, and
      carbohydrate intakes and/or a Western pattern derived by principal component
      analysis). CONCLUSIONS: In this large prospective study, a 10% increase in the
      proportion of ultra-processed foods in the diet was associated with a significant
      increase of greater than 10% in risks of overall and breast cancer. Further
      studies are needed to better understand the relative effect of the various
      dimensions of processing (nutritional composition, food additives, contact
      materials, and neoformed contaminants) in these associations. STUDY REGISTRATION:
      Clinicaltrials.gov NCT03335644.

PMID- 29444773
TI  - Lung Function, Inflammation, and Endothelin-1 in Congenital Heart Disease
      Associated Pulmonary Arterial Hypertension.
AB  - BACKGROUND: Breathlessness is the most common symptom in people with pulmonary
      arterial hypertension and congenital heart disease (CHD-APAH), previously thought
      to be caused by worsening PAH, but perhaps also by inflammation and abnormalities
      of lung function. We studied lung function and airway inflammation in patients
      with CHD-APAH and compared the results with controls. METHODS AND RESULTS: Sixty
      people were recruited into the study: 20 CHD-APAH, 20 CHD controls, and 20
      healthy controls. Spirometry, gas transfer, whole body plethysmography and lung
      clearance index, 6-minute walk distance, and medical research council dyspnea
      scoring were performed. Inflammatory markers and endothelin-1 levels were
      determined in blood and induced sputum. The CHD-APAH group had abnormal lung
      function with lung restriction, airway obstruction, and ventilation
      heterogeneity. Inverse correlations were shown for CHD-APAH between medical
      research council dyspnea score and percent predicted peak expiratory flow (r=
      0.5383, P=0.0174), percent predicted forced expiratory flow rate at 50% of forced
      vital capacity (r=-0.5316, P=0.0192), as well as for percent predicted forced
      expiratory volume in 1 s (r=-0.6662, P=0.0018) and percent predicted forced vital
      capacity (r=-0.5536, P=0.0186). The CHD-APAH patients were more breathless with
      lower 6-minute walk distance (360 m versus 558 m versus 622 m, P=0.00001).
      Endothelin-1, interleukin (IL)-beta, IL-6, IL-8, tumor necrosis factor alpha, and
      vascular endothelial growth factor were significantly higher in CHD-APAH than
      controls. Serum endothelin-1 for CHD-APAH correlated with airflow obstruction
      with significant negative correlations with percent predicted forced expiratory
      flow rate at 75% of forced vital capacity (r=-0.5858, P=0.0135). CONCLUSIONS:
      Raised biomarkers for inflammation were found in CHD-APAH. Significant
      abnormalities in airway physiology may contribute to the dyspnea but are not
      driven by inflammation as assessed by circulating and sputum cytokines. A
      relationship between increased serum endothelin-1 and airway dysfunction may
      relate to its bronchoconstrictive properties.

PMID- 29444775
TI  - Persistent inequalities in Hospice at Home provision.
AB  - OBJECTIVE: To describe the nature and scope of a new Hospice at Home (H@H)
      service and to identify its equality of provision. METHODS: Case note review of
      patients supported by a H@H service for 1 year from September 2012 to August 2013
      (n=321). Descriptive analysis to report frequencies and proportions of
      quantitative data extracted from service logs, referral forms and care records;
      thematic analysis of qualitative data from care record free text. RESULTS: Demand
      outstripped supply. Twice as many night care episodes were requested (n=1237) as
      were provided (n=613). Inequalities in access to the service related to
      underlying diagnosis and socioeconomic status. 75% of patients using the service
      had cancer (221/293 with documented diagnosis). Of those who died at home in the
      areas surrounding the hospice, 53% (163/311) of people with cancer and 11%
      (49/431) of those without cancer received H@H support. People who received H@H
      care were often more affluent than the population average for the area within
      which they lived. Roles of the service identified included: care
      planning/implementation, specialist end-of-life care assessment and advice,
      'holding' complex patients until hospice beds become available and clinical
      nursing care. CONCLUSION: There is significant unmet need and potentially large
      latent demand for the H@H service. People without cancer or of lower
      socioeconomic status are less likely to access the service. Action is needed to
      ensure greater and more equitable service provision in this and similar services
      nationally and internationally.

PMID- 29444774
TI  - Comparison Between Different Strategies of Rheumatic Heart Disease
      Echocardiographic Screening in Brazil: Data From the PROVAR (Rheumatic Valve
      Disease Screening Program) Study.
AB  - BACKGROUND: Considering the limited accuracy of clinical examination for early
      diagnosis of rheumatic heart disease (RHD), echocardiography has emerged as an
      important epidemiological tool. The ideal setting for screening is yet to be
      defined. We aimed to evaluate the prevalence and pattern of latent RHD in
      schoolchildren (aged 5-18 years) and to compare effectiveness of screening
      between public schools, private schools, and primary care centers in Minas
      Gerais, Brazil. METHODS AND RESULTS: The PROVAR (Rheumatic Valve Disease
      Screening Program) study uses nonexperts and portable and handheld devices for
      RHD echocardiographic screening, with remote interpretation by telemedicine,
      according to the 2012 World Heart Federation criteria. Compliance with study
      consent and prevalence were compared between different screening settings, and
      variables associated with RHD were analyzed. In 26 months, 12 048 students were
      screened in 52 public schools (n=10 901), 2 private schools (n=589), and 3
      primary care centers (n=558). Median age was 12.9 years, and 55.4% were girls.
      Overall RHD prevalence was 4.0% borderline (n=486) and 0.5% definite (n=63), with
      statistically similar rates between public schools (4.6%), private schools
      (3.5%), and primary care centers (4.8%) (P=0.24). The percentage of informed
      consents signed was higher in primary care centers (84.4%) and private schools
      (66.9%) compared with public schools (38.7%) (P<0.001). Prevalence was higher in
      children >=12 years (5.3% versus 3.1%; P<0.001) and girls (4.9% versus 4.0%;
      P=0.02). Only age (odds ratio, 1.12; 95% confidence interval, 1.09-1.17; P<0.001)
      was independently associated with RHD. CONCLUSIONS: RHD screening in primary care
      centers seems to achieve higher coverage rates. Prevalence among schoolchildren
      is significantly high, with rates higher than expected in private schools of high
      income areas. These data are important for the formulation of public policies to
      confront RHD.

PMID- 29444776
TI  - Association between spectral characteristics of paraspinal muscles and functional
      disability in patients with low back pain: a cohort study.
AB  - OBJECTIVES: Characteristics of muscle activity, represented by surface
      electromyography (EMG), have revealed differences between patients with low back
      pain (LBP) and healthy adults; how they relate to functional and clinical
      parameters remains unclear. The purpose of the current study was to examine the
      correlation between frequency characteristics of EMG (analysed using continuous
      wavelet transform (CWT) analysis) and patients' self-rated score of disability.
      DESIGN AND SETTING: This is a case-control study with 15 patients with mechanical
      LBP without radicular symptoms. Patients were recruited from the orthopaedic
      clinic at Charing Cross Hospital. Ten healthy adults were recruited from the
      staff working in the hospital and associated university. Patients completed the
      Roland-Morris Disability Questionnaire (RMDQ) and bilateral EMG activity was
      obtained from erector spinae at vertebral levels L4 and T12. Subjects performed
      three brief maximal voluntary isometric contractions (MVICs) of the back
      extensors and the torque was measured using a dynamometer. CWT was applied to the
      EMG signals of each muscle in a 200 ms window centred around the peak torque
      obtained during the MVICs. The ratio (low/high frequencies) of the energy, the
      peak power and the frequency of the peak power were calculated for each recording
      site, averaged and correlated with the individual's RMDQ score. RESULTS: Patients
      had lower peak power (T12 and L4) and lower frequency of the peak power (at T12)
      than the healthy adults. Additionally, RMDQ positively correlated to the average
      ratio of energy at T12 (r=0.63; p=0.012), that is, greater self-rated disability
      corresponded to a dominant distribution of energy in the lower frequencies.
      CONCLUSION: The current findings reveal alterations in EMG profile and its
      association with self-related back pain disability, suggesting that spectral
      characteristics of EMG reflect muscle function.

PMID- 29444777
TI  - Estimates of prevalence, demographic characteristics and social factors among
      people with disabilities in the USA: a cross-survey comparison.
AB  - OBJECTIVE: A national priority for disability research in the USA is the
      standardised identification of people with disabilities in surveillance efforts.
      Mandated by federal statute, six dichotomous difficulty-focused questions were
      implemented in national surveys to identify people with disabilities. The aim of
      this study was to assess the prevalence, demographic characteristics and social
      factors among people with disabilities based on these six questions using
      multiple national surveys in the USA. SETTING: American Community Survey (ACS),
      Current Population Survey Annual Social and Economic Supplement (CPS-ASEC),
      National Health Interview Survey (NHIS) and the Survey of Income and Program
      Participation (SIPP). PARTICIPANTS: Civilian, non-institutionalised US residents
      aged 18 and over from the 2009 to 2014 ACS, 2009 to 2014 CPS-ASEC, 2009 to 2014
      NHIS and 2008 SIPP waves 3, 7 and 10. PRIMARY AND SECONDARY OUTCOME MEASURES:
      Disability was assessed using six standardised questions asking people about
      hearing, vision, cognition, ambulatory, self-care and independent living
      disabilities. Social factors were assessed with questions asking people to report
      their education, employment status, family size, health and marital status,
      health insurance and income. RESULTS: Risk ratios and demographic distributions
      for people with disabilities were consistent across survey. People with
      disabilities were at decreased risk of having college education, employment,
      families with three or more people, excellent or very good self-reported health
      and a spouse. People with disabilities were also consistently at greater risk of
      having health insurance and living below the poverty line. Estimates of
      disability prevalence varied between surveys from 2009 to 2014 (range 11.76%
      17.08%). CONCLUSION: Replicating the existing literature, we found the estimation
      of disparities and inequity people with disabilities experience to be consistent
      across survey. Although there was a range of prevalence estimates, demographic
      factors for people with disabilities were consistent across surveys. Variations
      in prevalence estimates can be explained by survey context effects.

PMID- 29444778
TI  - Efficacy and safety of the Shexiang Baoxin Pill for the treatment of coronary
      artery disease not amenable to revascularisation: study protocol for a
      randomised, placebo-controlled, double-blinded trial.
AB  - INTRODUCTION: Coronary artery disease (CAD) not amenable to revascularisation
      indicates that the coronary arteries have severe diffuse lesions or
      calcifications, or that CAD is complicated with severe multiple-organ disease.
      Currently, Western medicines available for the treatment of CAD not amenable to
      revascularisation are limited. Shexiang Baoxin Pill (SBP), a type of Chinese
      patent medicine, has been widely used to treat CAD in China for many years.
      Previous studies have shown that long-term administration of SBP (1-2 pills three
      times daily, for at least 6 months) for treatment of CAD is effective and safe,
      with a significant, long-term effect. This study aims to evaluate the efficacy
      and safety of SBP in patients with CAD not amenable to revascularisation. METHODS
      AND ANALYSIS: This is a multicentre, randomised, double-blinded, placebo
      controlled clinical trial. A total of 440 participants will be randomly allocated
      to two groups: the intervention group and the placebo group. Based on
      conventional treatment with Western medicine, the intervention group will be
      treated with SBP and the placebo group will be treated with SBP placebo. The
      primary outcomes include major adverse cardiovascular events (including angina,
      acute myocardial infarction, pulmonary embolism and aortic dissection). The
      secondary outcomes include C reactive protein, B-type natriuretic peptide, ECG,
      echocardiographic parameters (ejection fraction percentage and the E/A ratio) and
      hospital readmission rates due to CAD. Assessments will be performed at baseline
      (before randomisation) and at 24 weeks after randomisation. ETHICS AND
      DISSEMINATION: The protocol has been approved by the Research Ethics Committee of
      Guang'anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China
      (reference: 2016-129-KY-01). The results of this study will be published in a
      peer-reviewed journal and will be used as a basis for a multisite trial. TRIAL
      REGISTRATION NUMBER: NCT03072121; Pre-results.

PMID- 29444779
TI  - Estimating the met need for emergency obstetric care (EmOC) services in three
      payams of Torit County, South Sudan: a facility-based, retrospective cross
      sectional study.
AB  - OBJECTIVE: To determine the met need for emergency obstetric care (EmOC) services
      in three Payams of Torit County, South Sudan in 2015 and to determine the
      frequency of each major obstetric complication. DESIGN: This was a retrospective
      cross-sectional study. SETTING: Four primary healthcare centres (PHCCs) and one
      state hospital in three payams (administrative areas that form a county) in Torit
      County, South Sudan. PARTICIPANTS: All admissions in the obstetrics and
      gynaecology wards (a total of 2466 patient admission files) in 2015 in all the
      facilities designated to conduct deliveries in the study area were reviewed to
      identify obstetric complications. PRIMARY AND SECONDARY OUTCOME MEASURES: The
      primary outcome was met need for EmOC, which was defined as the proportion of all
      women with direct major obstetric complications in 2015 treated in health
      facilities providing EmOC services. The frequency of each complication and the
      interventions for treatment were the secondary outcomes. RESULTS: Two hundred and
      fifty four major obstetric complications were admitted in 2015 out of 390
      expected from 2602 pregnancies, representing 65.13% met need. The met need was
      highest (88%) for Nyong Payam, an urban area, compared with the other two rural
      payams, and 98.8% of the complications were treated from the hospital, while no
      complications were treated from three PHCCs. The most common obstetric
      complications were abortions (45.7%), prolonged obstructed labour (23.2%) and
      haemorrhage (16.5%). Evacuation of the uterus for retained products (42.5%),
      caesarean sections (32.7%) and administration of oxytocin for treatment of
      postpartum haemorrhage (13.3%) were the most common interventions. CONCLUSION:
      The met need for EmOC in Torit County is low, with 35% of women with major
      obstetric complications not accessing care, and there is disparity with Nyong
      Payam having a higher met need. We suggest more support supervision to the PHCCs
      to increase access for the rural population.

PMID- 29444781
TI  - Do quality improvement initiatives for diabetes care address social inequities?
      Secondary analysis of a systematic review.
AB  - BACKGROUND: Socially disadvantaged populations carry a disproportionate burden of
      diabetes-related morbidity and mortality. There is an emerging interest in
      quality improvement (QI) strategies in the care of patients with diabetes,
      however, the effect of these interventions on disadvantaged groups remains
      unclear. OBJECTIVE: This is a secondary analysis of a systematic review that
      seeks to examine the extent of equity considerations in diabetes QI studies,
      specifically quantifying the proportion of studies that target interventions
      toward disadvantaged populations and conduct analyses on the impact of
      interventions on disadvantaged groups. RESEARCH DESIGN AND METHODS: Studies were
      identified using Medline, HealthStar and the Cochrane Effective Practice and
      Organisation of Care database. Randomised controlled trials assessing 12 QI
      strategies targeting health systems, healthcare professionals and/or patients for
      the management of adult outpatients with diabetes were eligible. The place of
      residence, race/ethnicity/culture/language, occupational status, gender/sexual
      identity, religious affiliations, education level, socioeconomic status, social
      capital, plus age, disability, sexual preferences and relationships (PROGRESS
      Plus) framework was used to identify trials that focused on disadvantaged patient
      populations, to examine the types of equity-relevant factors that are being
      considered and to explore temporal trends in equity-relevant diabetes QI trials.
      RESULTS: Of the 278 trials that met the inclusion criteria, 95 trials had equity
      relevant considerations. These include 64 targeted trials that focused on a
      disadvantaged population with the aim to improve the health status of that
      population and 31 general trials that undertook subgroup analyses to assess the
      extent to which their interventions may have had differential impacts on
      disadvantaged subgroups. Trials predominantly focused on race/ethnicity,
      socioeconomic status and place of residence as potential factors for disadvantage
      in patients receiving diabetes care. CONCLUSIONS: Less than one-third of diabetes
      QI trials included equity-relevant considerations, limiting the relevance and
      applicability of their data to disadvantaged populations. There is a need for
      better data collection, reporting, analysis and interventions on the social
      determinants of health that may influence the health outcomes of patients with
      diabetes. PROSPERO REGISTRATION NUMBER: CRD42013005165.

PMID- 29444780
TI  - The possible link between coeliac and Kawasaki diseases in Brazil: a cross
      sectional study.
AB  - BACKGROUND: Kawasaki disease (KD) is a self-limited acute systemic vasculitis of
      unknown aetiology that predominantly affects infants and young children
      eventually associated with immunological abnormalities. Coeliac disease (CD) is
      an inflammatory autoimmune disease characterised by a permanent gluten
      intolerance, which affects genetically susceptible individuals of any age group,
      and can cause intestinal and systemic symptoms. Association of CD with KD has
      been previously described in a single study that disclosed a surprisingly high
      prevalence of CD in children with a history of KD. OBJECTIVE: To confirm the
      existence of a higher prevalence of CD among individuals with a history of KD,
      which would turn the screening for CD in patients with history of KD highly
      advisable. SETTING: Children with history of KD, diagnosed and followed at the
      Rheumatology Clinic of the Children's Hospital of Brasilia (Brasilia, Brazil).
      PARTICIPANTS: This study included 110 children with history of KD and a control
      group composed of 110 presumably healthy children. INTERVENTIONS: Participants
      underwent anti-transglutaminase and anti-endomysial antibodies tests and genetic
      typing for the presence of CD predisposing alleles (HLA-DQ2 and DQ8). Jejunal
      biopsy was performed when necessary, according the European Society of Paediatric
      Gastroenterology, Hepatology and Nutrition guidelines. RESULTS: Diagnosis of CD
      was confirmed in one (0.91%) patient with KD by positive serological tests,
      presence of predisposing alleles and CD typical lesions on duodenal biopsy. All
      serological tests were negative among the controls. The prevalence of CD
      predisposing alleles among patients with KD was 29.09%, similar to the prevalence
      found among controls, 33.64%. CONCLUSION: The detected CD prevalence (0.91%) does
      not confirm the existence of an association between KD and CD since this
      prevalence is similar to that found in the general population (?1%).

PMID- 29444782
TI  - Are efforts to attract graduate applicants to UK medical schools effective in
      increasing the participation of under-represented socioeconomic groups? A
      national cohort study.
AB  - INTRODUCTION: Attracting graduates was recommended as a means of diversifying the
      UK medical student population. Graduates now make up nearly a quarter of the
      total medical student population. Research to date has focused on comparing the
      sociodemographic characteristics of applicants to and/or students on traditional
      and graduate entry programmes (GEMs), yet GEMs account for only 40% of the
      graduate medical student population. Thus, we aimed to compare the
      sociodemographic characteristic and outcomes of graduates and non-graduate
      applicants across a range of programmes. METHODS: This was an observational study
      of 117 214 applicants to medicine who took the UK Clinical Aptitude Test (UKCAT)
      from 2006 to 2014 and who applied to medical school through Universities and
      Colleges Admissions Service (UCAS). We included applicant demographics, UKCAT
      total score and offers in our analysis. Applicants were assigned as graduates or
      non-graduates on the basis of their highest qualification. Multiple logistic
      regression was used to predict the odds of receiving an offer, after adjusting
      for confounders. RESULTS: Irrespective of graduate or non-graduate status, most
      applicants were from the highest socioeconomic groups and were from a white
      ethnic background. Receiving an offer was related to gender and ethnicity in both
      graduates and non-graduates. After adjusting for UKCAT score, the OR of an offer
      for graduates versus non-graduates was approximately 0.5 (OR=0.48, 95% CI 0.46 to
      0.49). DISCUSSION: Our findings indicate that the aim of diversifying the medical
      student population on socioeconomic grounds by attracting graduates has been only
      marginally successful. Graduate applicants from widening access backgrounds are
      less likely than others to be offered a place at medical school. Different
      approaches must be considered if medicine is to attract and select more socially
      diverse applicants.

PMID- 29444783
TI  - Mortality and quality of death certification in a cohort of patients with
      Parkinson's disease and matched controls in North Wales, UK at 18 years: a
      community-based cohort study.
AB  - OBJECTIVE: This investigation reports the cause and the quality of death
      certification in a community cohort of patients with Parkinson's disease (PD) and
      controls at 18 years. SETTING: Denbighshire North Wales, UK. PARTICIPANTS: The
      community-based cohorts consisted of 166 patients with PD and 102 matched
      controls. PRIMARY OUTCOMES: All-cause mortality was ascertained at 18 years by
      review of hospitals' primary care records and examination of death certificates
      obtained from the UK General Register Office. Mortality HRs were estimated using
      Cox proportional regression, controlling for covariates including age at study
      entry, age at death, gender, motor function, mood, health-related quality of life
      (HRQoL) and cognitive function. RESULTS: After 18 years, 158 (95%) of patients in
      the PD cohort and 34 (33%) in the control cohort had died. Compared with the
      general UK population, the PD cohort had a higher risk of mortality (standard
      mortality rate, 1.82, 95% CI 1.55 to 2.13). As the primary or underlying cause of
      death, PD was not reported in 75/158 (47%) of the death certificates. In
      addition, although 144/158 (91%) of the PD cohort had a diagnosis of dementia,
      this was reported in less than 10% of death certificates. The main cause of death
      reported in the PD cohort was pneumonia (53%), followed by cardiac-related deaths
      (21%). Compared with controls, patients with PD had a greater risk of pneumonia
      (2.03, 95% CI 1.34 to 3.6), poorer HRQoL and more likely to reside in
      institutional care at death (P<0.01). CONCLUSION: This investigation found that
      PD was associated with an excess risk of mortality compared with the general
      population. However, PD as a primary or underlying cause of death recorded on
      certificates was found to be suboptimal. This suggests that the quality of
      mortality statistics drawn from death certificates alone is not a valid or
      reliable source of data.

PMID- 29444784
TI  - A scoping review protocol to map the evidence on interventions to prevent
      overweight and obesity in children.
AB  - INTRODUCTION: Obesity has become one of the biggest public health problems of the
      21st century. Prevalence of obesity in children and adolescents has increased
      dramatically worldwide over the last 20 years, and this trend is expected to
      continue. Obesity in childhood is concerning as it predicts obesity in adulthood,
      a common risk factor for a wide array of chronic diseases and poor health
      outcomes. Obesity is preventable and a vast but fragmented body of evidence on
      preventative interventions is now available. This article outlines the protocol
      for a scoping review of published literature reviews on interventions to prevent
      obesity in children. The scoping review addresses the broad research question
      'What is the evidence on interventions to prevent childhood obesity?'. It aims to
      give an overview of the various interventions available, understand those which
      are effective and identify barriers and facilitators to their effectiveness.
      METHODS AND ANALYSIS: The six-staged Arksey and O'Malley methodology framework is
      used to guide the scoping review process: following the definition of the
      research questions (stage 1); the eligibility criteria and search strategy are
      defined (stage 2); the study selection process based on the eligibility criteria
      identified will follow (stage 3); a framework developed for this review will then
      inform the extraction and charting of data from the included reviews (stage 4);
      results will be aggregated and summarised with criteria relevant for health
      professionals and policy-makers (stage 5); and the optional consultation (stage
      6) exercise is not planned. ETHICS AND DISSEMINATION: Since the scoping review
      methodology aims at synthetising information from available publications, this
      study does not require ethical approval. An article reporting the results of the
      scoping review will be submitted for publication to a scientific journal,
      presented at relevant conferences and disseminated as part of future workshops
      with professionals involved in obesity prevention.

PMID- 29444785
TI  - Longitudinal changes in intraocular pressure and association with systemic
      factors and refractive error: Lingtou Eye Cohort Study.
AB  - OBJECTIVES: To investigate the longitudinal changes in intraocular pressure (IOP)
      and its associations with refractive error and systemic determinants in a Chinese
      geriatric population. DESIGN: Prospective cohort study. SETTING: Guangzhou
      Government Servant Physical Check-up Center, Guangzhou, China. PARTICIPANTS: 4413
      government employees aged no less than 40 years (41.9% female) attending annual
      physical and eye examinations were included in this study. The inclusion
      criterion was having attended the 2010 follow-up examination. The exclusion
      criteria include glaucoma or intraocular surgery history, IOP >21 mm Hg at any
      visit or without available IOP data at all visits from 2010 to 2014. PRIMARY AND
      SECONDARY OUTCOME MEASURES: The outcome measure was IOP at each follow-up visit
      from 2010 to 2014. Mixed-effect model was used to assess the relationship between
      longitudinal changes in IOP and potential risk factors. RESULTS: For the 2653
      participants who had available IOP data at both the 2010 and 2014 follow-up
      visits, the average change in IOP was an increase of 0.43 (95% CI 0.36 to 0.50)
      mm Hg. For the whole study population and in the optimised mixed model, there was
      a non-linear increase of IOP with age (P<0.001), with greater changes in younger
      subjects and in women (P<0.001 and P=0.002, respectively). Elevations in systolic
      blood pressure, diastolic blood pressure, body mass index (BMI) and fasting
      plasma glucose (FPG), as well as a myopic shift (all with P<0.001), during the
      follow-up were associated with an increasing trend of IOP, while serum lipids
      were found to be not significantly associated. CONCLUSIONS: In this cohort of
      elderly Chinese adults, IOP increases non-linearly with ageing. People with
      increasing blood pressure, BMI, FPG and myopic progression are more likely to
      have IOP elevation over time.

PMID- 29444786
TI  - Task sharing to improve the prevention, diagnosis and management of rheumatic
      heart disease: a systematic review protocol.
AB  - INTRODUCTION: Rheumatic heart disease (RHD) remains an important cause of
      cardiovascular morbidity and mortality globally due to weak health systems in
      many countries. RHD can be effectively prevented and managed; however, RHD
      related interventions have not been widely adopted in countries with severe human
      resource constraints. Task sharing is a recognised approach to personnel
      shortages that could prove effective for RHD and has, anecdotally, been attempted
      in a few settings. We propose a systematic review and meta-analysis protocol to
      assess models that use non-physician workers to expand access to, and quality of,
      RHD-related healthcare. METHODS: We will include randomised controlled trials
      (RCT), cluster RCTs, quasi-experimental and controlled before and after studies
      providing information on the effectiveness of non-physician workers in providing
      care for streptoccocal pharyngitis, rheumatic fever and RHD. We will search
      relevant electronic databases and grey literature using medical subject headings.
      Standardised data extraction forms will be used to collect effect sizes that will
      be pooled in random-effects models. We will also conduct subgroup analyses and
      note other important quantitative findings, such as cost reduction, and
      qualitative findings, such as patient satisfaction. We will also assess study
      quality and risk of bias and metabias. ETHICS AND DISSEMINATION: Ethics approval
      is not required for this systematic review of previously published literature.
      The results of the systematic review will be broadly disseminated via conference
      presentations, multidisciplinary workshops and peer-reviewed publications.
      PROSPERO REGISTRATION NUMBER: CRD42017072989.

PMID- 29444787
TI  - Randomised controlled pragmatic clinical trial evaluating the effectiveness of a
      discharge follow-up phone call on 30-day hospital readmissions: balancing
      pragmatic and explanatory design considerations.
AB  - INTRODUCTION: Hospital readmissions within 30 days are a healthcare quality
      problem associated with increased costs and poor health outcomes. Identifying
      interventions to improve patients' successful transition from inpatient to
      outpatient care is a continued challenge. METHODS AND ANALYSIS: This is a single
      centre pragmatic randomised and controlled clinical trial examining the
      effectiveness of a discharge follow-up phone call to reduce 30-day inpatient
      readmissions. Our primary endpoint is inpatient readmission within 30 days of
      hospital discharge censored for death analysed with an intention-to-treat
      approach. Secondary endpoints included observation status readmission within 30
      days, time to readmission, all-cause emergency department revisits within 30
      days, patient satisfaction (measured as mean Hospital Consumer Assessment of
      Healthcare Providers and Systems scores) and 30-day mortality. Exploratory
      endpoints include the need for assistance with discharge plan implementation
      among those randomised to the intervention arm and reached by the study nurse,
      and the number of call attempts to achieve successful intervention delivery.
      Consistent with the Learning Healthcare System model for clinical research,
      timeliness is a critical quality for studies to most effectively inform hospital
      clinical practice. We are challenged to apply pragmatic design elements in order
      to maintain a high-quality practicable study providing timely results. This type
      of prospective pragmatic trial empowers the advancement of hospital-wide evidence
      based practice directly affecting patients. ETHICS AND DISSEMINATION: Study
      results will inform the structure, objective and function of future iterations of
      the hospital's discharge follow-up phone call programme and be submitted for
      publication in the literature. TRIAL REGISTRATION NUMBER: NCT03050918; Pre
      results.

PMID- 29444789
TI  - Giant cell tumour of the patella with local recurrence: successful management
      with excision, curettage and artificial bone grafting.
AB  - Primary patellar neoplasms are rare, comprising 0.12% of primary bone tumours;
      thus, no standardised treatment related to staging exists. 70%-90% of primary
      patellar neoplasms are benign or intermediate with giant cell tumour (GCT) being
      the most common. GCTs are locally aggressive, have a high recurrence rate and
      metastasise in 1%-2%. We report the case of a 23-year-old man with histologically
      confirmed recurrent GCT of the patella to demonstrate that aggressive surgical
      management options described in the literature, such as patellectomy with or
      without complex reconstruction, may be excessive and cause patients undue
      morbidity. Initially, the patient underwent intralesional curettage with
      excellent recovery, but presented again with a local recurrence within a year. A
      further definitive operation was performed which included excision of the
      inferior pole followed by curettage of the patellar body and artificial bone
      grafting. The patient made a good recovery and at 5-year follow-up has maintained
      good function.

PMID- 29444788
TI  - Assessment of the societal and individual preferences for fertility treatment in
      Australia: study protocol for stated preference discrete choice experiments.
AB  - INTRODUCTION: In Australia, societal and individual preferences for funding
      fertility treatment remain largely unknown. This has resulted in a lack of
      evidence about willingness to pay (WTP) for fertility treatment by either the
      general population (the funders) or infertile individuals (who directly benefit).
      Using a stated preference discrete choice experiment (SPDCE) approach has been
      suggested as a more appropriate method to inform economic evaluations of
      fertility treatment. We outline the protocol for an ongoing study which aims to
      assess fertility treatment preferences of both the general population and
      infertile individuals, and indirectly estimate their WTP for fertility treatment.
      METHODS AND ANALYSIS: Two separate but related SPDCEs will be conducted for two
      population samples-the general population and infertile individuals-to elicit
      preferences for fertility treatment to indirectly estimate WTP. We describe the
      qualitative work to be undertaken to design the SPDCEs. We will use D-efficient
      fractional experimental designs informed by prior coefficients from the pilot
      surveys. The mode of administration for the SPDCE is also discussed. The final
      results will be analysed using mixed logit or latent class model. ETHICS AND
      DISSEMINATION: This study is being funded by the Australian National Health and
      Medical Research Council (NHMRC) project grant AP1104543 and has been approved by
      the University of New South Wales Human Research Ethics Committee (HEC 17255) and
      a fertility clinic's ethics committee. Findings of the study will be disseminated
      in peer-reviewed journals and presented at various conferences. A lay summary of
      the results will be made publicly available on the University of New South Wales
      National Perinatal Epidemiology and Statistics Unit website. Our results will
      contribute to the development of an evidence-based policy framework for the
      provision of cost-effective and patient-centred fertility treatment in Australia.

PMID- 29444791
TI  - The J-sign in patellar maltracking.

PMID- 29444790
TI  - Localised nasopharyngeal amyloidosis: the importance of postoperative follow-up.
AB  - Localised nasopharyngeal amyloidosis is rare. Findings on physical examination
      and invasive pattern on CT scan can be misleading as it can resemble
      nasopharyngeal carcinoma. A 64-year-old man presented with left aural fullness
      for 6 months. The physical examination showed straw-coloured fluid in the left
      middle ear and irregular reddish mass at the left side of the nasopharynx. The CT
      scan showed a lobulated heterogeneous mass at the left side of the nasopharynx
      involving the left Eustachian tube opening. Pathology report was amyloidosis,
      thus, surgery was done. After a year, there were new foci of amyloidosis at the
      right side of the nasopharynx, and a repeat surgery was performed. Two years
      later, the systemic amyloidosis with underlying IgG4-related disease was
      suspected due to multiple organ involvement. Surgery is the treatment for
      localised amyloidosis with compressive symptoms. Close follow-up is important
      after surgical excision due to its recurrence and progression to systemic
      amyloidosis.

PMID- 29444792
TI  - Intestinal obstruction caused by a strangulating adnexa: a rare complication of
      ovarian sparing hysterectomy.
AB  - Intestinal obstruction caused by a remnant fallopian tube from previous
      hysterectomy is a rare entity that has been reported once in the literature. We
      report the case of a 61-year-old woman who presented with both small and large
      bowel obstructions caused by a strangulating remnant fallopian tube. She had an
      ovarian sparing hysterectomy 16 years ago and was diagnosed with antiphospholipid
      syndrome. Our case report will discuss the clinical presentation, imaging and
      outcome of the patient. It will also briefly tackle other rare causes of bowel
      obstruction.

PMID- 29444793
TI  - Isolated bladder schwannoma: a rare presentation.
AB  - Bladder schwannoma is a rare tumour arising from Schwann cells in nerve sheaths.
      It is usually more common in patients diagnosed with neurofibromatosis. However,
      isolated cases of urinary bladder schwannoma is incredibly rare, attributing to
      <0.1% of bladder tumours. A literature review and analysis revealed that it
      presents in adulthood, is mostly symptomatic and diagnosis is established
      histologically. We report a case of isolated bladder schwannoma in 25 year-old
      female who presented with dyspareunia.

PMID- 29444794
TI  - Spontaneous bilateral quadriceps tendon rupture in a patient with renal failure.

PMID- 29444795
TI  - Agenesis of dorsal pancreas in a young adult: a rare cause of diabetes mellitus.
AB  - Dorsal pancreatic agenesis is an extremely rare entity characterised by absence
      of body and tail of pancreas, while there are so many other developmental
      anomalies of the pancreas that have been reported. Here we report a 25-year-old
      young man who presented with pain in the abdomen, recurrent loose stools and
      hyperglycaemia. On radiological imaging study, there was complete agenesis of the
      dorsal pancreas except for thin stripe of tissue at the level of the uncinate
      process. Both exocrinedysfunction and endocrine dysfunction were present in this
      patient. Patient was supplemented with pancreatic enzyme preparation and insulin.

PMID- 29444796
TI  - Biopsy-proven multiple sclerosis in an adult patient with atypical
      craniometaphyseal dysplasia.
AB  - Craniometaphyseal dysplasia (CMD) is a rare condition characterised by
      progressive, diffuse hyperostosis of cranial and long bones, with compression of
      cranial nerves, linked to mutations in ANKH or GJA1 genes. Here we describe an
      adult case with clinical features of CMD, who developed cerebral expansive lesion
      of undetermined nature. Brain biopsy revealed active demyelinating lesions,
      consistent with multiple sclerosis. The genetic screening of target genes for CMD
      (ANKH and GJA1) resulted negative in this patient. The peculiar clinical
      association and the negativity of genetic analyses allow to hypothesise that
      other genetic causes, not already known, are responsible for the combination of
      these pathological conditions. Future studies aim to identify the genetic causes
      of CMD, which will be important to further understand the pathogenetic mechanism
      of this rare and invalidating disease.

PMID- 29444797
TI  - Paediatric Clostridium difficile pseudomembranous colitis: a complication of
      refractory constipation?

PMID- 29444798
TI  - Epitrochlear lymphadenitis mimicking subcutaneous abscess.

PMID- 29444799
TI  - Salvage from cervical dystocia in third degree uterovaginal prolapse: Duhrssen's
      incision.
AB  - We present a case of a 28-year-old woman second gravida with a full-term
      pregnancy who presented to us in active phase of labour with third degree
      uterovaginal prolapse complicated by entrapment of fetal head by dystocia of
      cervix and fetal distress. Patient was immediately shifted to the operation
      theatre and prompt delivery was conducted by giving Duhrssen's incision on the
      highly vascular, oedematous prolapsed cervix. The outcome was an alive and
      healthy male baby. Duhrssen's incision was stitched with minimal blood loss.
      Postnatal management included antibiotics and daily intravaginal packing. Patient
      was discharged along with the baby in satisfactory condition.

PMID- 29444800
TI  - Uncommon but potential life-threatening complication after tonsillectomy: post
      tonsillectomy cervicofacial surgical emphysema.

PMID- 29444801
TI  - Widespread and precise reprogramming of yeast protein-genome interactions in
      response to heat shock.
AB  - Gene expression is controlled by a variety of proteins that interact with the
      genome. Their precise organization and mechanism of action at every promoter
      remains to be worked out. To better understand the physical interplay among
      genome-interacting proteins, we examined the temporal binding of a functionally
      diverse subset of these proteins: nucleosomes (H3), H2AZ (Htz1), SWR (Swr1), RSC
      (Rsc1, Rsc3, Rsc58, Rsc6, Rsc9, Sth1), SAGA (Spt3, Spt7, Ubp8, Sgf11), Hsf1,
      TFIID (Spt15/TBP and Taf1), TFIIB (Sua7), TFIIH (Ssl2), FACT (Spt16), Pol II
      (Rpb3), and Pol II carboxyl-terminal domain (CTD) phosphorylation at serines 2,
      5, and 7. They were examined under normal and acute heat shock conditions, using
      the ultrahigh resolution genome-wide ChIP-exo assay in Saccharomyces cerevisiae
      Our findings reveal a precise positional organization of proteins bound at most
      genes, some of which rapidly reorganize within minutes of heat shock. This
      includes more precise positional transitions of Pol II CTD phosphorylation along
      the 5' ends of genes than previously seen. Reorganization upon heat shock
      includes colocalization of SAGA with promoter-bound Hsf1, a change in RSC subunit
      enrichment from gene bodies to promoters, and Pol II accumulation within
      promoter/+1 nucleosome regions. Most of these events are widespread and not
      necessarily coupled to changes in gene expression. Together, these findings
      reveal protein-genome interactions that are robustly reprogrammed in precise and
      uniform ways far beyond what is elicited by changes in gene expression.

PMID- 29444802
TI  - Building Support for Adolescent Sexuality and Reproductive Health Education and
      Responding to Resistance in Conservative Contexts: Cases From Pakistan.
AB  - BACKGROUND: Despite international recommendations and supportive evidence, there
      are few examples of scaled-up and sustained programs to provide adolescents with
      sexuality education. Moreover, despite acknowledgment that building community
      support and responding to resistance are key challenges, there is a lack of
      detailed discussion on specific programmatic strategies to address these issues.
      OBJECTIVES: This article reviews the work of 2 organizations-Aahung and Rutgers
      Pakistan-that are successfully implementing large-scale sexuality education
      programs in Pakistan, collectively reaching more than 500,000 students. This
      review aims to answer the following questions: (1) How did Aahung and Rutgers
      Pakistan work to understand Pakistani society and culture and shape their
      programs to build community support? (2) How did Aahung and Rutgers Pakistan
      overcome resistance to their efforts? METHODS: We reviewed program documents and
      publications, synthesized key themes, identified questions of interest, and
      engaged key informants from Aahung and Rutgers Pakistan's leadership. RESULTS:
      The success of Aahung and Rutgers Pakistan was grounded in their readiness to
      understand the nuanced context within the communities, collaborate with groups of
      stakeholders-including parents, school officials, religious leaders, media
      personnel, and adolescents themselves-to ensure support, and stand up to forces
      of resistance to pursue their goals. Specific strategies included working with
      communities to select content, tactfully selecting and framing issues with
      careful consideration for sensitivities, engaging adolescents' influencers,
      strengthening media presence, showcasing school programs to increase
      understanding and transparency, and choosing opportune times to introduce
      messages. CONCLUSION: The successful strategies used by Aahung and Rutgers
      Pakistan to promote adolescent sexual and reproductive health through sexuality
      education can inform programs worldwide. Additionally, the programmatic
      weaknesses identified can guide future planning and action by Aahung and Rutgers
      Pakistan. We call on other programs to continue sharing challenges, specifically
      related to resistance, with sexuality education programs in order to develop a
      toolbox of additional strategies for community uptake.

PMID- 29444803
TI  - Open-source recombinant monoclonal secondary nanobodies.
AB  - Secondary antibodies are everyday reagents in biomedical research that are
      generated in animals. In this issue, Pleiner et al. (2018. J. Cell Biol.
      https://doi.org/10.1083/jcb.201709115) describe several single domain antibody
      fragments against antibodies from mouse and rabbit, so-called nanobodies that are
      easily produced recombinantly, and characterize their use in Western blotting,
      enzyme-linked immunosorbent assay, and immunofluorescence assays.

PMID- 29444804
TI  - Partitioning the Pleiotropy Between Coronary Artery Disease and Body Mass Index
      Reveals the Importance of Low Frequency Variants and Central Nervous System
      Specific Functional Elements.
AB  - BACKGROUND: The objective of this study is to investigate the extent and nature
      of pleiotropy between coronary artery disease (CAD) and body mass index (BMI).
      METHODS: We examined the contribution of genome-wide single-nucleotide
      polymorphisms (minor allele frequency >=0.01) to co-occurrence of CAD and BMI in
      a sample of genetically unrelated 8041 subjects (genetic resemblance <=0.025) of
      European ancestry using mixed-linear-models. We further partitioned the estimated
      pleiotropy according to biological features to gain insight into the nature of
      pleiotropy between CAD and BMI. RESULTS: We found significant (P<0.0001) positive
      genetic correlation between CAD and BMI (rg =0.60). The estimated pleiotropy
      explained 68% of phenotypic correlation, and it was not proportionally
      distributed across the chromosomes; notably, chromosome 10 contributed more;
      whereas, chromosomes 11 and 14 contributed less to pleiotropy than expected given
      their chromosomal length. We noted that a large proportion (63%; P=0.002) of the
      pleiotropy is attributed to single-nucleotide polymorphisms with low allele
      frequency (minor allele frequency <0.05). Of note, pleiotropy was enriched among
      central nervous system genes and genes of metabolic pathways. Further analyses
      revealed that these effects are more pronounced in the proopiomelanocortin
      pathway and genes involved in carbohydrate metabolism. After genome-wide
      association study meta-analysis, only single-nucleotide polymorphisms downstream
      of the MC4R gene were found concordantly associated with (P<5*10-8) BMI and CAD
      with lead single-nucleotide polymorphism being rs663129 (combined P=2.7*10-65).
      Finally, partitioning the pleiotropy according to functional elements pointed to
      the importance of superenhancers and notably brain-specific superenhancers.
      CONCLUSIONS: Genome-wide pleiotropy substantially contributes to co-occurrence of
      CAD and obesity, and it is highly enriched among low frequency variants and
      central nervous system-specific functional elements.

PMID- 29444807
TI  - Hypoxic Challenge Testing (Fitness to Fly) in children with complex congenital
      heart disease.
AB  - OBJECTIVE: Commercial airplanes fly with an equivalent cabin fraction of inspired
      oxygen of 0.15, leading to reduced oxygen saturation (SpO2) in passengers. How
      this affects children with complex congenital heart disease (CHD) is unknown. We
      conducted Hypoxic Challenge Testing (HCT) to assess need for inflight
      supplemental oxygen. METHODS: Children aged <16 years had a standard HCT. They
      were grouped as (A) normal versus abnormal baseline SpO2 (>=95% vs <95%) and (B)
      absence versus presence of an actual/potential right-to-left (R-L) shunt. We
      measured SpO2, heart rate, QT interval corrected for heart rate and partial
      pressure of carbon dioxide measured transcutaneously (PtcCO2). A test failed when
      children with (1) normal baseline SpO2 desaturated to 85%, (2) baseline SpO285%
      94% desaturated by 15% of baseline; and (3) baseline SpO275%-84% desaturated to
      70%. RESULTS: There were 68 children, mean age 3.3 years (range 10 weeks-14.5
      years). Children with normal (n=36) baseline SpO2 desaturated from median 99% to
      91%, P<0.0001, and 3/36 (8%) failed the test. Those with abnormal baseline SpO2
      (n=32) desaturated from median 84% to 76%, P<0.0001, and 5/32 (16%) failed (no
      significant difference between groups). Children with no R-L shunt (n=25)
      desaturated from median 99% to 93%, P<0.0001, but 0/25 failed. Those with an
      actual/potential R-L shunt (n=43) desaturated from median 87% to 78%, P<0.0001,
      and 8/43 (19%) failed (difference between groups P<0.02). PtcCO2, heart rate and
      QT interval corrected for heart rate were unaffected by the hypoxic state.
      CONCLUSIONS: This is the first evidence to help guide which children with CHD
      need a preflight HCT. We suggest all children with an actual or potential R-L
      shunt should be tested.

PMID- 29444805
TI  - A Reassessment of Genes Modulating Aging in Mice Using Demographic Measurements
      of the Rate of Aging.
AB  - Many studies have reported genetic interventions that have an effect on mouse
      life span; however, it is crucial to discriminate between manipulations of aging
      and aging-independent causes of life extension. Here, we used the Gompertz
      equation to determine whether previously reported aging-related mouse genes
      statistically affect the demographic rate of aging. Of 30 genetic manipulations
      previously reported to extend life span, for only two we found evidence of
      retarding demographic aging: Cisd2 and hMTH1 Of 24 genetic manipulations reported
      to shorten life span and induce premature aging features, we found evidence of
      five accelerating demographic aging: Casp2, Fn1, IKK-beta, JunD, and Stub1
      Overall, our reassessment found that only 15% of the genetic manipulations
      analyzed significantly affected the demographic rate of aging as predicted,
      suggesting that a relatively small proportion of interventions affecting
      longevity do so by regulating the rate of aging. By contrast, genetic
      manipulations affecting longevity tend to impact on aging-independent mortality.
      Our meta-analysis of multiple mouse longevity studies also reveals substantial
      variation in the controls used across experiments, suggesting that a short life
      span of controls is a potential source of bias. Overall, the present work leads
      to a reassessment of genes affecting the aging process in mice, with broad
      implications for our understanding of the genetics of mammalian aging and which
      genes may be more promising targets for drug discovery.

PMID- 29444806
TI  - Multiple Applications of a Transient CRISPR-Cas9 Coupled with Electroporation
      (TRACE) System in the Cryptococcus neoformans Species Complex.
AB  - Cryptococcus neoformans is a fungal pathogen that claims hundreds of thousands of
      lives annually. Targeted genetic manipulation through biolistic transformation in
      C. neoformans drove the investigation of this clinically important pathogen at
      the molecular level. Although costly and inefficient, biolistic transformation
      remains the major method for editing the Cryptococcus genome as foreign DNAs
      introduced by other methods such as electroporation are predominantly not
      integrated into the genome. Although the majority of DNAs introduced by biolistic
      transformation are stably inherited, the transformation efficiency and the
      homologous integration rate (~1-10%) are low. Here, we developed a Transient
      CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 coupled
      with Electroporation (TRACE) system for targeted genetic manipulations in the C.
      neoformans species complex. This method took advantages of efficient genome
      integration due to double-strand breaks created at specific sites by the
      transient CRISPR-Cas9 system and the high transformation efficiency of
      electroporation. We demonstrated that TRACE can efficiently generate precise
      single-gene deletion mutants using the ADE2 locus as an example. This system can
      also effectively delete multiple genes in a single transformation, as evident by
      the successful generation of quadruple mfalpha1Delta2Delta3Delta4Delta mutants.
      In addition to generating gene deletion mutants, we complemented the ade2Delta
      mutant by integrating a wild-type ADE2 allele at the "safe haven" region (SH2)
      via homologous recombination using TRACE. Interestingly, introduced DNAs can be
      inserted at a designated genetic site without any homologous sequences, opening
      up numerous other applications. We expect that TRACE, an efficient, versatile,
      and cost-effective gene editing approach, will greatly accelerate research in
      this field.

PMID- 29444808
TI  - Cochrane corner: PCSK9 monoclonal antibodies for the primary and secondary
      prevention of cardiovascular disease.

PMID- 29444810
TI  - Disharmonious Patterns of Heterotaxy and Isomerism: How Often Are the Classic
      Patterns Breached?
AB  - BACKGROUND: It is advocated that heterotaxy should be segregated into right or
      left isomerism according to atrial appendage morphology. However, atrial situs
      determination is often based on the pattern of associated findings rather than on
      atrial morphology itself, which can be difficult to define. The objective was to
      assess how often concordant patterns of isomerism classified by atrial appendage
      morphology, bronchopulmonary pattern, and splenic status are breached using
      cardiac magnetic resonance or computed tomography. The secondary objective was to
      determine the feasibility of defining atrial appendage morphology using cardiac
      magnetic resonance or computed tomography. METHODS AND RESULTS: Retrospective
      review of 114 pediatric patients (median, 2.4 years; range, 1 day-17.9 years)
      with heterotaxy who underwent cardiac magnetic resonance or computed tomography
      was performed to evaluate atrial appendage, bronchopulmonary, and visceral organ
      arrangements. Atrial appendage and splenic anatomy were not definable in 17 of
      114 (15%) and 4 of 114 (3.5%) patients, respectively. In the remaining 93
      patients, 39% had classic right isomerism (bilateral right atrial appendages,
      right bronchopulmonary pattern, and asplenia) and 40% had classic left isomerism
      (bilateral left atrial appendages, left bronchopulmonary pattern, and
      polysplenia). Classic pattern of isomerism was breached in 20 of 93 (21.5%)
      patients: 13 (65%) displayed incongruent abdominal situs, 5 (25%) incongruent
      bronchial situs, 1 (5%) had discrepant appendage morphology, and 1 (5%)
      incongruent situs at all levels. CONCLUSIONS: Atrial appendage morphology is
      difficult to assess and not always indicative of bronchopulmonary or abdominal
      situs. Discordance between bronchopulmonary branching, atrial appendage
      arrangement, and splenic status was identified in >20% patients with heterotaxy.
      Independent description of each organ system is required when arrangements are
      disharmonious among different organ systems.

PMID- 29444811
TI  - Clinical Usefulness of Dual-Energy Cardiac Computed Tomography in Acute Coronary
      Syndrome Using a Dual-Layer Spectral Detector Scanner.

PMID- 29444812
TI  - Classifying Heterotaxy Syndrome: Time for a New Approach.

PMID- 29444813
TI  - TEOSINTE BRANCHED1 Regulates Inflorescence Architecture and Development in Bread
      Wheat (Triticum aestivum).
AB  - The flowers of major cereals are arranged on reproductive branches known as
      spikelets, which group together to form an inflorescence. Diversity for
      inflorescence architecture has been exploited during domestication to increase
      crop yields, and genetic variation for this trait has potential to further boost
      grain production. Multiple genes that regulate inflorescence architecture have
      been identified by studying alleles that modify gene activity or dosage; however,
      little is known in wheat. Here, we show TEOSINTE BRANCHED1 (TB1) regulates
      inflorescence architecture in bread wheat (Triticum aestivum) by investigating
      lines that display a form of inflorescence branching known as "paired spikelets."
      We show that TB1 interacts with FLOWERING LOCUS T1 and that increased dosage of
      TB1 alters inflorescence architecture and growth rate in a process that includes
      reduced expression of meristem identity genes, with allelic diversity for TB1
      found to associate genetically with paired spikelet development in modern
      cultivars. We propose TB1 coordinates formation of axillary spikelets during the
      vegetative to floral transition and that alleles known to modify dosage or
      function of TB1 could help increase wheat yields.

PMID- 29444816
TI  - Quality-Improvement Effort to Reduce Hypothermia Among High-Risk Infants on a
      Mother-Infant Unit.
AB  - BACKGROUND AND OBJECTIVE: Neonatal hypothermia is common in low birth weight
      (LBW) (<2500 g) and late-preterm infants (LPIs) (34 0/7-36 6/7 weeks' gestation).
      It can be a contributory factor for newborn admission to a NICU, resulting in
      maternal-infant separation and increased resource use. Our objective was to study
      the efficacy of a quality-improvement bundle of hypothermia preventive measures
      for LPIs and/or LBW infants in a mother-infant unit. METHODS: We conducted plan
      do-study-act (PDSA) cycles aimed at decreasing environmental hypothermia for LPIs
      and/or LBW infants in a mother-infant unit with no other indications for NICU
      level care. Interventions included using warm towels after delivery, a risk
      identification card, an occlusive hat, delayed timing of first bath, submersion
      instead of sponge-bathing, and conducting all assessments under a radiant warmer
      during the initial hours of life. We implemented these interventions in 3 PDSA
      cycles and followed hypothermia rates by using statistical process control
      methods. RESULTS: The baseline mean monthly hypothermia rate among mother-infant
      unit LPIs and/or LBW infants was 29.8%. Postintervention, the rate fell to 13.3%
      (-16.5%; P = .002). This decrease occurred in a stepwise fashion in conjunction
      with the PDSA cycles. In the final, full-intervention period, the rate was 10.0%
      (-19.8%; P = .0003). A special-cause signal shift was observed in this final
      period. CONCLUSIONS: Targeted interventions can significantly reduce hypothermia
      in otherwise healthy LPIs and/or LBW newborns and allow them to safely remain in
      a mother-infant unit. If applied broadly, such preventive practices could
      decrease preventable hypothermia in high-risk populations.

PMID- 29444815
TI  - Molecular mechanisms of missense mutations that generate ectopic N-glycosylation
      sites in coagulation factor VIII.
AB  - N-glycosylation is a common posttranslational modification of secreted and
      membrane proteins, catalyzed by the two enzymatic isoforms of the
      oligosaccharyltransferase, STT3A and STT3B. Missense mutations are the most
      common mutations in inherited diseases; however, missense mutations that generate
      extra, non-native N-glycosylation sites have not been well characterized.
      Coagulation factor VIII (FVIII) contains five consensus N-glycosylation sites
      outside its functionally dispensable B domain. We developed a computer program
      that identified hemophilia A mutations in FVIII that can potentially create
      ectopic glycosylation sites. We determined that 18 of these ectopic sites indeed
      become N-glycosylated. These sites span the domains of FVIII and are primarily
      associated with a severe disease phenotype. Using STT3A and STT3B knockout cells,
      we determined that ectopic glycosylation exhibited different degrees of
      dependence on STT3A and STT3B. By separating the effects of ectopic N
      glycosylation from those due to underlying amino acid changes, we showed that
      ectopic glycans promote the secretion of some mutants, but impair the secretion
      of others. However, ectopic glycans that enhanced secretion could not
      functionally replace a native N-glycan in the same domain. Secretion-deficient
      mutants, but not mutants with elevated secretion levels, show increased
      association with the endoplasmic reticulum chaperones BiP (immunoglobulin heavy
      chain-binding protein) and calreticulin. Though secreted to different extents,
      all studied mutants exhibited lower relative activity than wild-type FVIII. Our
      results reveal differential impacts of ectopic N-glycosylation on FVIII folding,
      trafficking and activity, which highlight complex disease-causing mechanisms of
      FVIII missense mutations. Our findings are relevant to other secreted and
      membrane proteins with mutations that generate ectopic N-glycans.

PMID- 29444817
TI  - Strengthening the Connection of Medical Education to the Vision of Improving
      Child Health.

PMID- 29444814
TI  - Plastid Translation Elongation Factor Tu Is Prone to Heat-Induced Aggregation
      Despite Its Critical Role in Plant Heat Tolerance.
AB  - Translation elongation factor Tu (EF-Tu) is a conserved GTP-binding protein
      essential for protein translation in prokaryotes and in eukaryotic mitochondria
      and plastids. EF-Tu also has a GTP/GDP-independent chaperone activity that may
      function in acclimation to heat. Here, we report that the Arabidopsis
      (Arabidopsis thaliana) plastid EF-Tu, Rabe1b, rapidly becomes insoluble at
      temperatures as low as 35 degrees C in vitro and 41 degrees C in vivo, with more
      than 90% aggregation after 9 h at 45 degrees C in vivo. Based on its established
      function in protein translation, heat-induced aggregation likely inactivates
      Rabe1b. To determine the effect of heat-induced aggregation, we isolated an
      Arabidopsis rabe1b knockdown mutant and discovered it to be highly compromised in
      heat tolerance. Overexpression of constitutive GTP- or GDP-bound mutant forms of
      Rabe1b in Arabidopsis and virus-induced silencing of Rabe1b in tomato (Solanum
      lycopersicum) also reduced heat tolerance. Compromised heat tolerance in the
      Arabidopsis rabe1b mutant and in the lines overexpressing constitutive GTP- or
      GDP-bound mutant Rabe1b proteins was associated with reduced plastid translation
      under heat stress. The Arabidopsis rabe1b mutant also showed compromised heat
      induced expression of HsfA2 and its target genes. Constitutive overexpression of
      HsfA2 activated its target genes but only partially restored the heat tolerance
      of the rabe1b mutant. These results strongly suggest that the plastid protein EF
      Tu is heat sensitive and acts as a critical limiting factor in plant heat stress
      responses, primarily functioning in plastid protein translation but also in
      protein folding and retrograde signaling of nuclear heat-responsive gene
      expression.

PMID- 29444818
TI  - Sox7 promotes high-grade glioma by increasing VEGFR2-mediated vascular
      abnormality.
AB  - High-grade glioma (HGG) is highly angiogenic, but antiangiogenic therapy has
      transient clinical benefit in only a fraction of patients. Vascular regulators of
      these heterogeneous responses remain undetermined. We found up-regulation of Sox7
      and down-regulation of Sox17 in tumor endothelial cells (tECs) in mouse HGG. Sox7
      deletion suppressed VEGFR2 expression, vascular abnormality, hypoxia-driven
      invasion, regulatory T cell infiltration, and tumor growth. Conversely, Sox17
      deletion exacerbated these phenotypes by up-regulating Sox7 in tECs. Anti-VEGFR2
      antibody treatment delayed tumor growth by normalizing Sox17-deficient abnormal
      vessels with high Sox7 levels but promoted it by regressing Sox7-deficient
      vessels, recapitulating variable therapeutic responses to antiangiogenic therapy
      in HGG patients. Our findings establish that Sox7 promotes tumor growth via
      vessel abnormalization, and its level determines the therapeutic outcome of
      VEGFR2 inhibition in HGG. In 189 HGG patients, Sox7 expression was heterogeneous
      in tumor vessels, and high Sox7 levels correlated with poor survival, early
      recurrence, and impaired vascular function, emphasizing the clinical relevance of
      Sox7 in HGG.

PMID- 29444819
TI  - BACE1 deletion in the adult mouse reverses preformed amyloid deposition and
      improves cognitive functions.
AB  - BACE1 initiates the generation of the beta-amyloid peptide, which likely causes
      Alzheimer's disease (AD) when accumulated abnormally. BACE1 inhibitory drugs are
      currently being developed to treat AD patients. To mimic BACE1 inhibition in
      adults, we generated BACE1 conditional knockout (BACE1fl/fl) mice and bred
      BACE1fl/fl mice with ubiquitin-CreER mice to induce deletion of BACE1 after
      passing early developmental stages. Strikingly, sequential and increased deletion
      of BACE1 in an adult AD mouse model (5xFAD) was capable of completely reversing
      amyloid deposition. This reversal in amyloid deposition also resulted in
      significant improvement in gliosis and neuritic dystrophy. Moreover, synaptic
      functions, as determined by long-term potentiation and contextual fear
      conditioning experiments, were significantly improved, correlating with the
      reversal of amyloid plaques. Our results demonstrate that sustained and
      increasing BACE1 inhibition in adults can reverse amyloid deposition in an AD
      mouse model, and this observation will help to provide guidance for the proper
      use of BACE1 inhibitors in human patients.

PMID- 29444820
TI  - A modified, hypoallergenic variant of the  Ricinus communis Ric c1 protein
      retains biological activity.
AB  - Ric c1, an allergenic protein from Ricinus communis , is an insect alpha-amylase
      inhibitor that has become an occupational allergen. Ric c1 can cross-react with
      allergens from wheat, soybean, peanut, shrimp, fish, gluten, house dust, tobacco,
      and air fungus, thereby amplifying the concern and risks caused by Ricinus
      allergens. Two continuous IgE-binding epitopes were identified in Ric c1, both
      containing glutamic acid residues involved in IgE-binding and allergic
      challenges. We produced recombinant Ric c1 (rRic c1) in Escherichia coli , using
      primers from foliar R. communis DNA, and a mutant (Glu-Leu) recombinant protein
      (mrRic c1) in the same system using synthetic genes. rRic c1 preserved both
      allergenic and alpha-amylase inhibitory properties, and mrRic c1 drastically
      reduced allergenic properties. These results can help to establish meaningful
      relationships between structure, defense and allergenicity, important steps for
      producing engineered plants and developing new approaches for immunotherapy.

PMID- 29444821
TI  - A fusion protein composed of the DSL domain of Dll1 and RGD motif protects
      cryptic stem cells in irradiation injury.
AB  - Intestine is vulnerable to irradiation injury, which induces cell death and
      compromises regeneration of intestinal crypts. It is well accepted that cryptic
      stem cells, which are responsible for cryptic regeneration under physiological
      and pathological conditions, are controlled by multiple cell-intrinsic and
      environmental signals such as Notch signaling. Therefore, in the present study,
      we tested whether a soluble Notch ligand tethered to endothelial cells-mD1R-the
      Delta-Serrate-Lag2 (DSL) domain of mouse Notch ligand Delta-like1 fused with a
      RGD motif could protect cryptic cells from irradiation-induced intestinal injury.
      The result showed that administration of mD1R, which activated Notch signaling in
      intestinal cells, ameliorated loss of body weight and reduction of cryptic
      structures in intestine after total body irradiation (TBI) in mice. Histological
      staining showed that injection of mD1R after TBI promoted cryptic cell
      proliferation and reduced cell apoptosis in crypts. Immunofluorescence staining
      and reverse transcription (RT)-PCR showed that mD1R increased the level of Lgr5,
      Bmi1, Olfactomedin-4 (OLFM4), and IRIG1 in crypts, suggesting a protective effect
      on cryptic stem and progenitor cells after irradiation. Moreover, we found that
      administration of mD1R increased the number of Paneth cells and the mRNA level of
      Defa1, and the number Alcian Blue+ Goblet cells decreased first and then
      increased after irradiation, suggesting that mD1R promoted the maturation of the
      intestinal crypt after irradiation injury. Our data suggested that mD1R could
      serve as a therapeutic agent for the treatment of irradiation-induced intestinal
      injury.

PMID- 29444823
TI  - Introduction to the Thematic Minireview Series: Green biological chemistry.
AB  - Plants and their green cousins cyanobacteria and algae use sunlight to drive the
      chemistry that lets them grow, survive, and perform an amazing range of
      biochemical reactions. The ability of these organisms to use a freely available
      energy source makes them attractive as sustainable and renewable platforms for
      more than just food production. They are also a source of metabolic tools for
      engineering microbes for "green" chemistry. This Thematic Minireview Series
      discusses how green organisms capture light and protect their photosynthetic
      machinery from too much light; new structural snapshots of the clock complex that
      orchestrates signaling during the light/dark cycle; challenges for improving
      stress responses in crops; harnessing cyanobacteria as biofactories; and efforts
      to engineer microbes for "green" biopolymer production.

PMID- 29444822
TI  - The protein kinase PERK/EIF2AK3 regulates proinsulin processing not via protein
      synthesis but by controlling endoplasmic reticulum chaperones.
AB  - Loss-of-function mutations of the protein kinase PERK (EIF2AK3) in humans and
      mice cause permanent neonatal diabetes and severe proinsulin aggregation in the
      endoplasmic reticulum (ER), highlighting the essential role of PERK in insulin
      production in pancreatic beta cells. As PERK is generally known as a
      translational regulator of the unfolded protein response (UPR), the underlying
      cause of these beta cell defects has often been attributed to derepression of
      proinsulin synthesis, resulting in proinsulin overload in the ER. Using high
      resolution imaging and standard protein fractionation and immunological methods
      we have examined the PERK-dependent phenotype more closely. We found that whereas
      proinsulin aggregation requires new protein synthesis, global protein and
      proinsulin synthesis are down-regulated in PERK-inhibited cells, strongly arguing
      against proinsulin overproduction being the root cause of their aberrant ER
      phenotype. Furthermore, we show that PERK regulates proinsulin proteostasis by
      modulating ER chaperones, including BiP and ERp72. Transgenic overexpression of
      BiP and BiP knockdown (KD) both promoted proinsulin aggregation, whereas ERp72
      overexpression and knockdown rescued it. These findings underscore the importance
      of ER chaperones working in concert to achieve control of insulin production and
      identify a role for PERK in maintaining a functional balance among these
      chaperones.

PMID- 29444824
TI  - Kinesin-2 motors: Kinetics and biophysics.
AB  - Kinesin-2s are major transporters of cellular cargoes. This subfamily contains
      both homodimeric kinesins whose catalytic domains result from the same gene
      product and heterodimeric kinesins with motor domains derived from two different
      gene products. In this Minireview, we focus on the progress to define the
      biochemical and biophysical properties of the kinesin-2 family members. Our
      understanding of their mechanochemical capabilities has been advanced by the
      ability to identify the kinesin-2 genes in multiple species, expression and
      purification of these motors for single-molecule and ensemble assays, and
      development of new technologies enabling quantitative measurements of kinesin
      activity with greater sensitivity.

PMID- 29444825
TI  - Structure and function of a novel periplasmic chitooligosaccharide-binding
      protein from marine Vibrio bacteria.
AB  - Periplasmic solute-binding proteins in bacteria are involved in the active
      transport of nutrients into the cytoplasm. In marine bacteria of the genus
      Vibrio, a chitooligosaccharide-binding protein (CBP) is thought to be the major
      solute-binding protein controlling the rate of chitin uptake in these bacteria.
      However, the molecular mechanism of the CBP involvement in chitin metabolism has
      not been elucidated. Here, we report the structure and function of a recombinant
      chitooligosaccharide-binding protein from Vibrio harveyi, namely VhCBP, expressed
      in Escherichia coli Isothermal titration calorimetry revealed that VhCBP strongly
      binds shorter chitooligosaccharides ((GlcNAc) n , where n = 2, 3, and 4) with
      affinities that are considerably greater than those for glycoside hydrolase
      family 18 and 19 chitinases but does not bind longer ones, including insoluble
      chitin polysaccharides. We also found that VhCBP comprises two domains with
      flexible linkers and that the domain-domain interface forms the sugar-binding
      cleft, which is not long extended but forms a small cavity. (GlcNAc)2 bound to
      this cavity, apparently triggering a closed conformation of VhCBP. Trp-363 and
      Trp-513, which stack against the two individual GlcNAc rings, likely make a major
      contribution to the high affinity of VhCBP for (GlcNAc)2 The strong chitobiose
      binding, followed by the conformational change of VhCBP, may facilitate its
      interaction with an active-transport system in the inner membrane of Vibrio
      species.

PMID- 29444826
TI  - Polymerase theta-helicase efficiently unwinds DNA and RNA-DNA hybrids.
AB  - POLQ is a unique multifunctional replication and repair gene that encodes for a N
      terminal superfamily 2 helicase and a C-terminal A-family polymerase. Although
      the function of the polymerase domain has been investigated, little is understood
      regarding the helicase domain. Multiple studies have reported that polymerase
      theta-helicase (Poltheta-helicase) is unable to unwind DNA. However, it exhibits
      ATPase activity that is stimulated by single-stranded DNA, which presents a
      biochemical conundrum. In contrast to previous reports, we demonstrate that
      Poltheta-helicase (residues 1-894) efficiently unwinds DNA with 3'-5' polarity,
      including DNA with 3' or 5' overhangs, blunt-ended DNA, and replication forks.
      Poltheta-helicase also efficiently unwinds RNA-DNA hybrids and exhibits a
      preference for unwinding the lagging strand at replication forks, similar to
      related HELQ helicase. Finally, we find that Poltheta-helicase can facilitate
      strand displacement synthesis by Poltheta-polymerase, suggesting a plausible
      function for the helicase domain. Taken together, these findings indicate nucleic
      acid unwinding as a relevant activity for Poltheta in replication repair.

PMID- 29444828
TI  - Diagnosing Invasive Candidiasis.
AB  - Cultures are negative in ~50% of invasive candidiasis. Data are emerging for the
      performance of nonculture tests such as mannan/antimannan, Candida albicans germ
      tube antibody, 1,3-beta-d-glucan, PCR, and the T2Candida panel in diagnosing both
      candidemia and deep-seated candidiasis. In most settings, positive predictive
      values of nonculture test are low, and negative predictive values are high. For
      tests to be useful, clinicians must understand the pretest likelihood of invasive
      candidiasis and test performance for the most common disease manifestation in a
      given patient. This paper reviews nonculture Candida diagnostics and discusses
      how they might be used effectively in patient care.

PMID- 29444827
TI  - Site-specific polyubiquitination differentially regulates parathyroid hormone
      receptor-initiated MAPK signaling and cell proliferation.
AB  - G protein-coupled receptor (GPCR) signaling and trafficking are essential for
      cellular function and regulated by phosphorylation, beta-arrestin, and
      ubiquitination. The GPCR parathyroid hormone receptor (PTHR) exhibits time
      dependent reversible ubiquitination. The exact ubiquitination sites in PTHR are
      unknown, but they extend upstream of its intracellular tail. Here, using tandem
      MS, we identified Lys388 in the third loop and Lys484 in the C-terminal tail as
      primary ubiquitination sites in PTHR. We found that PTHR ubiquitination requires
      beta-arrestin and does not display a preference for beta-arrestin1 or -2. PTH
      stimulated PTHR phosphorylation at Thr387/Thr392 and within the Ser489-Ser493
      region. Such phosphorylation events may recruit beta-arrestin, and we observed
      that chemically or genetically blocking PTHR phosphorylation inhibits its
      ubiquitination. Specifically, Ala replacement at Thr387/Thr392 suppressed beta
      arrestin binding and inhibited PTHR ubiquitination, suggesting that PTHR
      phosphorylation and ubiquitination are interdependent. Of note, Lys-deficient
      PTHR mutants promoted normal cAMP formation, but exhibited differential mitogen
      activated protein kinase (MAPK) signaling. Lys-deficient PTHR triggered early
      onset and delayed ERK1/2 signaling compared with wildtype PTHR. Moreover,
      ubiquitination of Lys388 and Lys484 in wildtype PTHR strongly decreased p38
      signaling, whereas Lys-deficient PTHR retained signaling comparable to
      unstimulated wildtype PTHR. Lys-deficient, ubiquitination-refractory PTHR reduced
      cell proliferation and increased apoptosis. However, elimination of all 11 Lys
      residues in PTHR did not affect its internalization and recycling. These results
      pinpoint the ubiquitinated Lys residues in PTHR controlling MAPK signaling and
      cell proliferation and survival. Our findings suggest new opportunities for
      targeting PTHR ubiquitination to regulate MAPK signaling or manage PTHR-related
      disorders.

PMID- 29444829
TI  - Multiplex Immunochromatographic Detection of OXA-48, KPC, and NDM Carbapenemases:
      Impact of Inoculum, Antibiotics, and Agar.
AB  - For the rapid detection of carbapenemase-producing Enterobacteriaceae (CPE),
      immunochromatographic lateral flow tests (ICT) have recently been developed. The
      aim of this study was to assess the new multiplex ICT Resist-3 O.K.N. and to
      investigate if it can be performed directly from susceptibility testing plates.
      Additionally, the impact of the inoculum and carbapenem disks on sensitivity and
      specificity was evaluated. The new ICT was challenged using 63 carbapenem
      resistant Enterobacteriaceae (CRE) isolates, including 51 carbapenemase
      producers. It was assessed under five different conditions directly from Mueller
      Hinton agar (MHA): 1 MUl or 10 MUl of inoculum harvested in the absence of
      antibiotic pressure or 1 MUl taken from the inhibition zone of either an
      ertapenem, imipenem, or meropenem disk. The sensitivity of the ICT was 100% for
      OXA-48-like and KPC carbapenemases and 94.4% for the NDM carbapenemase with the 1
      MUl inoculum. When harvested adjacent to a carbapenem disk, the sensitivity
      increased to 100%. Additionally, with zinc-supplemented MHA, both the sensitivity
      increased and the NDM band became visible faster (mean time, 8 +/- 3.9 min for
      MHA compared to 1.9 +/- 1.5 min for MHA plus zinc; P = 0.0016). The specificity
      of the ICT was 100%. The Resist-3 O.K.N. ICT is a sensitive and rapid test for
      the detection of three highly prevalent carbapenemases. However, false-negative
      results for NDM can occur. We recommend an inoculum of 1 MUl that is harvested
      adjacent to an ertapenem or meropenem disk and the use of agars with sufficient
      zinc content to achieve the best performance.

PMID- 29444830
TI  - Characterization of a Vesivirus Associated with an Outbreak of Acute Hemorrhagic
      Gastroenteritis in Domestic Dogs.
AB  - Four of eleven affected dogs died despite aggressive treatment during a 2015
      focal outbreak of hemorrhagic gastroenteritis following a stay in a pet housing
      facility. Routine diagnostic investigations failed to identify a specific cause.
      Virus isolation from fresh necropsy tissues yielded a calicivirus with sequence
      homology to a vesivirus within the group colloquially known as the vesivirus 2117
      strains that were originally identified as contaminants in CHO cell bioreactors.
      In situ hybridization and reverse transcription-PCR assays of tissues from the
      four deceased dogs confirmed the presence of canine vesivirus (CaVV) nucleic
      acids that localized to endothelial cells of arterial and capillary blood
      vessels. CaVV nucleic acid corresponded to areas of necrosis and hemorrhage
      primarily in the intestinal tract, but also in the brain of one dog with
      nonsuppurative meningoencephalitis. This is the first report of an atypical
      disease association with a putative hypervirulent vesivirus strain in dogs, as
      all other known strains of CaVV appear to cause nonclinical infections or
      relatively mild disease. After identification of the CU-296 vesivirus strain from
      this outbreak, four additional CaVV strains were amplified from unrelated fecal
      specimens and archived stocks provided by other laboratories. Broader questions
      include the origins, reservoir(s), and potential for reemergence and spread of
      these related CaVVs.

PMID- 29444831
TI  - HIV-Associated Mycobacterium tuberculosis Bloodstream Infection Is Underdiagnosed
      by Single Blood Culture.
AB  - We assessed the additional diagnostic yield for Mycobacterium tuberculosis
      bloodstream infection (BSI) by doing more than one tuberculosis (TB) blood
      culture from HIV-infected inpatients. In a retrospective analysis of two cohorts
      based in Cape Town, South Africa, 72/99 (73%) patients with M. tuberculosis BSI
      were identified by the first of two blood cultures during the same admission,
      with 27/99 (27%; 95% confidence interval [CI], 18 to 36%) testing negative on the
      first culture but positive on the second. In a prospective evaluation of up to 6
      blood cultures over 24 h, 9 of 14 (65%) patients with M. tuberculosis BSI had M.
      tuberculosis grow on their first blood culture; 3 more patients (21%) were
      identified by a second independent blood culture at the same time point, and the
      remaining 2 were diagnosed only on the 4th and 6th blood cultures. Additional
      blood cultures increase the yield for M. tuberculosis BSI, similar to what is
      reported for nonmycobacterial BSI.

PMID- 29444833
TI  - Retraction for Falci et al., "Low Sensitivity of Lateral-Flow Device-Aspergillus
      in Patients with Probable and Proven Aspergillosis: Results from a Multicentre
      Evaluation".

PMID- 29444832
TI  - Differential Contributions of Specimen Types, Culturing, and 16S rRNA Sequencing
      in Diagnosis of Prosthetic Joint Infections.
AB  - Prosthetic joint failure is mainly caused by infection, aseptic failure (AF), and
      mechanical problems. Infection detection has been improved with modified culture
      methods and molecular diagnostics. However, comparisons between modified and
      conventional microbiology methods are difficult due to variations in specimen
      sampling. In this prospective, multidisciplinary study of hip or knee prosthetic
      failures, we assessed the contributions of different specimen types, extended
      culture incubations, and 16S rRNA sequencing for diagnosing prosthetic joint
      infections (PJI). Project specimens included joint fluid (JF), bone biopsy
      specimens (BB), soft-tissue biopsy specimens (STB), and swabs (SW) from the
      prosthesis, collected in situ, and sonication fluid collected from prosthetic
      components (PC). Specimens were cultured for 6 (conventional) or 14 days, and 16S
      rRNA sequencing was performed at study completion. Of the 156 patients enrolled,
      111 underwent 114 surgical revisions (cases) due to indications of either PJI (n
      = 43) or AF (n = 71). Conventional tissue biopsy cultures confirmed PJI in 28/43
      (65%) cases and refuted AF in 3/71 (4%) cases; one case was not evaluable. Based
      on these results, minor diagnostic adjustments were made. Fourteen-day cultures
      of JF, STB, and PC specimens confirmed PJI in 39/42 (93%) cases, and 16S rRNA
      sequencing confirmed PJI in 33/42 (83%) cases. One PJI case was confirmed with
      16S rRNA sequencing alone and five with cultures of project specimens alone.
      These findings indicated that JF, STB, and PC specimen cultures qualified as an
      optimal diagnostic set. The contribution of sequencing to diagnosis of PJI may
      depend on patient selection; this hypothesis requires further investigation.

PMID- 29444834
TI  - Accuracy of High-Throughput Nanofluidic PCR-Based Pneumococcal Serotyping and
      Quantification Assays Using Sputum Samples for Diagnosing Vaccine Serotype
      Pneumococcal Pneumonia: Analyses by Composite Diagnostic Standards and Bayesian
      Latent Class Models.
AB  - The lack of reliable diagnostic tests for detecting vaccine serotype pneumococcal
      pneumonia (VTPP) remains a challenging issue in pneumococcal vaccine studies.
      This study assessed the performances of high-throughput nanofluidic PCR-based
      pneumococcal serotyping and quantification assay methods using sputum samples
      (the nanofluidic sputum quantitative PCR [Sp-qPCR] assay) to diagnose 13-valent
      pneumococcal conjugate VTPP compared with the performance of the serotype
      specific urinary antigen detection (UAD) assay using urine samples. Adult
      pneumonia patients from Japan were enrolled in this study between September 2012
      and August 2014. Sputum samples were subjected to the nanofluidic Sp-qPCR assay,
      quantitatively cultured, and serotyped by the Quellung reaction (SpQt). Urine
      samples were tested by the UAD method. The diagnostic performances of these tests
      were assessed using composite reference standards and Bayesian latent class
      models (BLCMs). Among 244 total patients, 27 (11.1%) tested positive with the UAD
      assay, while 16 (6.6%) and 34 (13.9%) tested positive with the SpQt and
      nanofluidic Sp-qPCR assays, respectively, with a cutoff value of >=104 DNA
      copies/ml, which showed the maximum value of the Youden index. Using BLCMs, the
      estimated prevalence for VTPP was 12.9%, and the nanofluidic Sp-qPCR assay
      demonstrated the best performance (sensitivity, 90.2%; specificity, 96.9%),
      followed by UAD (sensitivity, 75.6%; specificity, 97.9%) and SpQt (sensitivity,
      45.8%; specificity, 99.5%). However, when a higher cutoff value of >=107 DNA
      copies/ml was applied, the performance of UAD became comparable to that of Sp
      qPCR. The vaccine serotype-specific pneumococcal DNA load in sputum among UAD
      positive patients was 3 logs higher than that among UAD-negative patients (P =
      0.036). The nanofluidic Sp-qPCR assay may be accurate and useful for detecting
      VTPP among adults.

PMID- 29444835
TI  - Retrospective Review of Treponema pallidum PCR and Serology Results: Are Both
      Tests Necessary?
AB  - There has been a resurgence of syphilis diagnoses in Australia. We investigated
      whether our Treponema pallidum PCR test provides any additional diagnostic
      information over syphilis serology (chemiluminescence immunoassay [CMIA],
      Treponema pallidum particle agglutination [TPPA] assay, and the rapid plasma
      reagin [RPR] flocculation test). A retrospective audit of all T. pallidum PCR
      requests that came through our laboratory from January 2010 to June 2017 was
      conducted; data collected included age, gender, site of swab, and results from T.
      pallidum PCR, syphilis serology, and herpes simplex virus 1 (HSV-1) and HSV-2
      PCRs. A total of 441 T. pallidum PCR tests were performed; on average, 3 T.
      pallidum PCRs per month were requested in 2011, and this rate increased to 17.2
      requests per month in 2017. A total of 323 patients had both T. pallidum PCR and
      syphilis serology performed, with 67% of swabs taken from the genitals. T.
      pallidum PCR gave positive results for 61/323 (19%) patients; of these 61
      patients, 59 (97%) also had positive syphilis serology results (T. pallidum PCR
      sensitivity, 68%; specificity, 99%; positive predictive value, 97%; negative
      predictive value, 89%). Syphilis serology was positive for 91/323 patients (28%);
      of these 91 patients, 61 (66%) were also T. pallidum PCR positive (syphilis
      serology sensitivity, 97%; specificity, 88%; positive predictive value, 60%;
      negative predictive value, 99%). The Cohen's kappa value was 0.74, indicating
      substantial agreement between the two tests. Our results show that most patients
      with positive T. pallidum PCR results also had positive syphilis serology.
      Therefore, T. pallidum PCR adds little clinical value over serology for the
      diagnosis of syphilis in certain clinical settings.

PMID- 29444836
TI  - Evaluation of the Elecsys Chagas Assay for Detection of Trypanosoma cruzi
      Specific Antibodies in a Multicenter Study in Europe and Latin America.
AB  - Serology is the preferred method to confirm a Chagas disease diagnosis and to
      screen blood donors. A battery of assays is often required due to the limited
      accuracy of single assays. The Elecsys Chagas assay is a newly developed, double
      antigen sandwich assay for use on the Elecsys and cobas e immunoassay analyzers,
      intended to identify individuals infected with Trypanosoma cruzi, for diagnosis
      and screening. The performance of the Elecsys Chagas assay was evaluated in
      comparison with those of other widely used T. cruzi antibody assays, at multiple
      sites (Europe/Latin America). Relative sensitivity and specificity were assessed
      by using samples from blood donors, pregnant women, and hospitalized patients
      from regions where Chagas disease is endemic and from regions of nonendemicity.
      The Elecsys Chagas assay had an overall relative sensitivity of 100% (n = 674).
      Overall relative specificities were 99.90% (n = 14,681), 100% (n = 313), and 100%
      (n = 517) for samples from blood donors, pregnant women, and hospitalized
      patients, respectively. The analytical specificity was 99.83% (n = 594). The
      Elecsys Chagas assay detected T. cruzi antibodies in two World Health
      Organization (WHO) standard T. cruzi reference panels (panels 09/188 and 09/186)
      at a 1:512 dilution, corresponding to a cutoff sensitivity of approximately 1
      mIU/ml. The Elecsys Chagas assay demonstrated robust performance under routine
      conditions at multiple sites in Europe and Latin America. In contrast to other
      available Chagas assays, the Elecsys assay uses a reduced number of recombinant
      T. cruzi antigens, resulting in a significantly smaller number of cross-reactions
      and improved analytical specificity while being highly sensitive.

PMID- 29444837
TI  - Whole-Genome Sequence Analysis of Streptococcus pneumoniae Strains That Cause
      Hospital-Acquired Pneumonia Infections.
AB  - Streptococcus pneumoniae colonizes the nasopharyngeal mucus in healthy
      individuals and can cause otitis media, pneumonia, and invasive pneumococcal
      diseases. In this study, we analyzed S. pneumoniae strains that caused 19
      pneumonia episodes in long-term inpatients with severe underlying disease in a
      hospital during a period of 14 months (from January 2014 to February 2015).
      Serotyping and whole-genome sequencing analyses revealed that 18 of the 19
      pneumonia cases were caused by S. pneumoniae strains belonging to 3 genetically
      distinct groups: clonal complex 9999 (CC9999), sequence type 282 (ST282), and
      ST166. The CC9999 and ST282 strains appeared to have emerged separately by a
      capsule switch from the pandemic PMEN 1 strain (Spain23F-ST81). After all the
      long-term inpatients were inoculated with the 23-valent pneumococcal
      polysaccharide vaccine, no other nosocomial pneumonia infections occurred until
      March 2016.

PMID- 29444838
TI  - Enzyme polymorphism, oxygen and injury: a lipidomic analysis of flight-induced
      oxidative damage in a succinate dehydrogenase d (Sdhd)-polymorphic insect.
AB  - When active tissues receive insufficient oxygen to meet metabolic demand,
      succinate accumulates and has two fundamental effects: it causes ischemia
      reperfusion injury while also activating the hypoxia-inducible factor pathway
      (HIF). The Glanville fritillary butterfly (Melitaea cinxia) possesses a balanced
      polymorphism in Sdhd, shown previously to affect HIF pathway activation and
      tracheal morphology and used here to experimentally test the hypothesis that
      variation in succinate dehydrogenase affects oxidative injury. We stimulated
      butterflies to fly continuously in a respirometer (3 min duration), which
      typically caused episodes of exhaustion and recovery, suggesting a potential for
      cellular injury from hypoxia and reoxygenation in flight muscles. Indeed, flight
      muscle from butterflies flown on consecutive days had lipidome profiles similar
      to those of rested paraquat-injected butterflies, but distinct from those of
      rested untreated butterflies. Many butterflies showed a decline in flight
      metabolic rate (FMR) on day 2, and there was a strong inverse relationship
      between the ratio of day 2 to day 1 FMR and the abundance of sodiated adducts of
      phosphatidylcholines and co-enzyme Q (CoQ). This result is consistent with
      elevation of sodiated lipids caused by disrupted intracellular ion homeostasis in
      mammalian tissues after hypoxia-reperfusion. Butterflies carrying the Sdhd M
      allele had a higher abundance of lipid markers of cellular damage, but the
      association was reversed in field-collected butterflies, where focal individuals
      typically flew for seconds at a time rather than continuously. These results
      indicate that Glanville fritillary flight muscles can be injured by episodes of
      high exertion, but injury severity appears to be determined by an interaction
      between SDH genotype and behavior (prolonged versus intermittent flight).

PMID- 29444839
TI  - Reverse genetics demonstrate the role of mucosal C-type lectins in food particle
      selection in the oyster Crassostrea virginica.
AB  - Prey selection governs species interactions and regulates physiological
      energetics of individuals and populations. Suspension-feeding bivalves represent
      key species in coastal and estuarine systems for their ecological and economic
      value. These animals are able to sort and selectively ingest nutritious
      microalgae from dilute and composite mixtures of particulate matter. This
      aptitude was suggested to be mediated by interactions between carbohydrates
      associated with the surface of microalgae and C-type lectins present in mucus
      covering the feeding organs, although a direct, unequivocal, role of lectins in
      food sorting in bivalves remains elusive. This study was designed to identify and
      characterize mucosal C-type lectins from oysters and manipulate the expression of
      these proteins in order to obtain decisive information regarding their
      involvement in food choice. Thus, two mucosal C-type lectins (CvML3912 and
      CvML3914) were identified based on transcriptomic and proteomic information.
      Transcripts of these lectins were detected in the feeding organs and their
      expression was upregulated following starvation. Recombinant lectin (rCvML3912)
      competitively inhibited the binding of commercial mannose/glucose-specific
      lectins to microalgae. Short Dicer-substrate small interfering RNA (DsiRNA)
      targeting these two lectins were designed and used to evaluate the effect of gene
      silencing on food particle sorting. As a result, the abundance of the two cognate
      transcripts significantly decreased and food sorting ability was significantly
      reduced among silenced oysters as compared with control animals. Overall, these
      findings propose a novel concept establishing the role of carbohydrate-protein
      interactions to provide efficient food particle sorting, and establish a new
      dimension for the role of evolutionarily conserved mannose/glucose-binding
      proteins in metazoans.

PMID- 29444840
TI  - Intestinal alpha-glycosidase transcriptional responses during development and
      diet adjustment in altricial birds.
AB  - We describe developmental changes in maltasic activity and its mRNA until
      adulthood, and in response to an increase in dietary starch. We studied house
      sparrows (Passer domesticus), which undergo a natural switch from insects to a
      starch-containing seed diet during development, and zebra finches (Taeniopygia
      guttata), which have a relatively fixed starchy seed diet during development. In
      zebra finches, in which maltasic activity increased with age but not with dietary
      starch, alpha-glycosidase (AG) mRNA was not affected by either age or dietary
      starch level. In house sparrow nestlings, in which maltasic activity increased
      with age and with added starch, AG mRNA was higher when birds were fed a diet
      with added starch but did not increase with age. These results are consistent
      with the idea that the apparent programmed developmental increase in maltasic
      activity is not mainly under transcriptional control of AG mRNA, whereas
      induction of maltasic activity by increased dietary starch is.

PMID- 29444841
TI  - Measuring metabolic rates of small terrestrial organisms by fluorescence-based
      closed-system respirometry.
AB  - We explore a recent, innovative variation of closed-system respirometry for
      terrestrial organisms, whereby oxygen partial pressure (PO2 ) is repeatedly
      measured fluorometrically in a constant-volume chamber over multiple time points.
      We outline a protocol that aligns this technology with the broader literature on
      aerial respirometry, including the calculations required to accurately convert O2
      depletion to metabolic rate (MR). We identify a series of assumptions, and
      sources of error associated with this technique, including thresholds where O2
      depletion becomes limiting, that impart errors to the calculation and
      interpretation of MR. Using these adjusted calculations, we found that the
      resting MR of five species of angiosperm seeds ranged from 0.011 to 0.640 ml g-1
      h-1, consistent with published seed MR values. This innovative methodology
      greatly expands the lower size limit of terrestrial organisms that can be
      measured, and offers the potential for measuring MR changes over time as a result
      of physiological processes of the organism.

PMID- 29444842
TI  - Task-specific sensory coding strategies are matched to detection and
      discrimination performance.
AB  - The acquisition of sensory information is limited by the neural encoding method
      used, constraining perceptual abilities. The most relevant aspects of stimuli may
      change as behavioral context changes, making efficient encoding of information
      more challenging. Sensory systems must balance rapid detection of a stimulus with
      perception of fine details that enable discrimination between similar stimuli.
      Here, we show that in a species of weakly electric fish, Apteronotus
      leptorhynchus, two coding strategies are employed for these separate behavioral
      tasks. Using communication signals, we demonstrate a strong correlation between
      neural coding strategies and behavioral performance on a discrimination task.
      Extracellular recordings of pyramidal cells within the electrosensory lateral
      line lobe of alert fish show two distinct response patterns, either burst
      discharges with little variation between different signals of the same category,
      or a graded, heterogeneous response that contains sufficient information to
      discriminate between signals with slight variations. When faced with a
      discrimination-based task, the behavioral performance of the fish closely matches
      predictions based on coding strategy. Comparisons of these results with neural
      and behavioral responses observed in other model systems suggest that our study
      highlights a general principle in the way sensory systems utilize different
      neural codes.

PMID- 29444843
TI  - Testing the parasite mass burden effect on alteration of host behaviour in the
      Schistocephalus-stickleback system.
AB  - Many parasites with complex life cycles modify the behaviour of their
      intermediate host, which has been proposed to increase transmission to their
      definitive host. This behavioural change could result from the parasite actively
      manipulating its host, but could also be explained by a mechanical effect, where
      the physical presence of the parasite affects host behaviour. We created an
      artificial internal parasite using silicone injections in the body cavity to test
      this mechanical effect hypothesis. We used the Schistocephalus solidus and
      threespine stickleback (Gasterosteus aculeatus) system, as this cestode can reach
      up to 92% of its fish host mass. Our results suggest that the mass burden brought
      by this macroparasite alone is not sufficient to cause behavioural changes in its
      host. Furthermore, our results show that wall-hugging (thigmotaxis), a measure of
      anxiety in vertebrates, is significantly reduced in Schistocephalus-infected
      sticklebacks, unveiling a new altered component of behaviour that may result from
      manipulation by this macroparasite.

PMID- 29444844
TI  - The stomatogastric nervous system of the medicinal leech: its anatomy, physiology
      and associated aminergic neurons.
AB  - Blood feeding is an essential and signature activity of the medicinal leech
      species Hirudo verbana. Despite keen interest in understanding the neuronal
      substrates of this behavior, a major component of the nervous system associated
      with feeding has remained overlooked. In this study, for the first time, we
      report on the presence and characteristics of five stomatogastric ganglia (STGs)
      comprising the visceral stomatogastric nervous system (STN) of the leech.
      Although a brief report was published by Ruth Hanke in 1948 indicating that a
      ring of three ganglia (not five) was associated with the cephalic ganglia, this
      information was never integrated into subsequent neurobiological studies of
      feeding. Here, the anatomical features of the STGs are described, as are the
      morphological and electrophysiological characteristics of neurons originating in
      them. We also determined that two of the five STGs (STG-1 and STG-3) each
      contained two relatively large (ca. 40 um diameter) serotonergic neurons. The STN
      was also enriched with dopaminergic and serotonergic arborizations; however, no
      intrinsic dopaminergic somata were observed. The trajectory of the serotonergic
      large lateral (LL) neuron, a command-like cell for feeding, was documented to
      project directly to the STN and not to the jaw and pharyngeal musculature as
      previously reported, thus reopening the important question of how the LL cell
      activates and coordinates biting activity with pharyngeal swallowing. Additional
      studies revealed that the LL cell is excited by blood serum applied to the lip
      and is strongly inhibited by dopamine. These findings provide a new foundation
      for understanding the regulation and modulation of neural networks involved in
      feeding.

PMID- 29444845
TI  - Antibacterial activity of male and female sperm-storage organs in ants.
AB  - Bacteria can damage sperm and thus reduce the reproductive success of both males
      and females; selection should therefore favour the evolution of antimicrobial
      protection. Eusocial hymenopterans might be particularly affected by such
      bacterial infections because of their mating ecology. In both sexes, mating is
      restricted to a short window early in the adult stage; there are no further
      chances to mate later in life. Males die shortly after mating, but queens use the
      acquired sperm to fertilise their eggs for years, sometimes decades. The
      reproductive success of both sexes is, thus, ultimately sperm-limited, which
      maintains strong selection for high sperm viability before and after storage. We
      tested the antibacterial activity of the contents of the male and female sperm
      storage organs - the accessory testes and the spermatheca, respectively. As our
      study species, we used the bacterium Escherichia coli and the garden ant Lasius
      niger, whose queens can live for several decades. Our results provide the first
      empirical evidence that male and female sperm-storage organs display different
      antibacterial activity. While the contents of the accessory testes actually
      enhanced bacterial growth, the contents of the spermatheca strongly inhibited it.
      Furthermore, mating appears to activate the general immune system in queens.
      However, antimicrobial activity in both the spermatheca and the control tissue
      (head-thorax homogenate) declined rapidly post-mating, consistent with a trade
      off between immunity and reproduction. Overall, this study suggests that
      ejaculates undergo an immune 'flush' at the time of mating, allowing storage of
      sperm cells free of bacteria.

PMID- 29444846
TI  - Differential immune gene expression in sperm storage organs of leaf-cutting ants.
AB  - Leaf-cutting ant queens mate with multiple males during a single nuptial flight
      and store sperm for up to two decades. During mating, males transfer sperm from
      their accessory testes to the queen bursa copulatrix from where it enters the
      spermatheca, an insect sperm storage organ that has become highly specialized in
      long-lived ant queens who never re-mate later in life. Long-term storage without
      the possibility to obtain new sperm creates an immune defence dilemma, because
      recognition of non-self cells eliminates infections but may also target
      irreplaceable sperm and reduce lifetime reproductive success. We therefore
      hypothesized that non-specific immune responses, like pathogen melanization,
      should be silenced in the spermatheca, because they rely on general non-self
      recognition, and that specific responses such as antimicrobial peptides are
      activated instead as they specifically target pathogenic bacteria and/or fungi.
      The maintenance of uninfected sperm cells by males before mating is not
      constrained by non-self recognition, meaning immune regulation might be more
      liberal in male reproductive organs. To test this hypothesis, we measured gene
      expression of two antimicrobial peptides, abaecin and defensin, and
      prophenoloxidase, an important enzyme of the melanization pathway, in male
      accessory glands and testes and in queen bursae copulatrix and spermathecae of
      Acromyrmex echinatior and Atta colombica leaf-cutting ants. As expected,
      prophenoloxidase expression was low in reproductive organs that sustain prolonged
      contact with sperm, whereas antimicrobial peptides showed average to high
      expression, indicating that leaf-cutting ants invest in specific rather than
      generalist immune defences for pathogen protection in organs that store sperm.

PMID- 29444847
TI  - Turnover of muscle lipids and response to exercise differ between neutral and
      polar fractions in a model songbird, the zebra finch.
AB  - The turnover rates of tissues and their constituent molecules give us insights
      into animals' physiological demands and their functional flexibility over time.
      Thus far, most studies of this kind have focused on protein turnover, and few
      have considered lipid turnover despite an increasing appreciation of the
      functional diversity of this class of molecules. We measured the turnover rates
      of neutral and polar lipids from the pectoralis muscles of a model songbird, the
      zebra finch (Taeniopygia guttata, N=65), in a 256 day C3/C4 diet shift
      experiment, with tissue samples taken at 10 time points. We also manipulated the
      physiological state of a subset of these birds with a 10 week flight training
      regimen to test the effect of exercise on lipid turnover. We measured lipid
      delta13C values via isotope ratio mass spectrometry (IRMS) and estimated turnover
      in different fractions and treatment groups with non-linear mixed-effect
      regression. We found a significant difference between the mean retention times
      (tau) of neutral and polar lipids (t119=-2.22, P=0.028), with polar lipids
      (tau=11.80+/-1.28 days) having shorter retention times than neutral lipids
      (tau=19.47+/-3.22 days). When all birds were considered, we also found a
      significant decrease in the mean retention time of polar lipids in exercised
      birds relative to control birds (difference=-2.2+/-1.83 days, t56=-2.37,
      P=0.021), but not neutral lipids (difference=4.2+/- 7.41 days, t56=0.57, P=0.57).
      A larger, more variable neutral lipid pool and the exposure of polar lipids in
      mitochondrial membranes to oxidative damage and increased turnover provide
      mechanisms consistent with our results.

PMID- 29444848
TI  - A miniaturized threshold-triggered acceleration data-logger for recording burst
      movements of aquatic animals.
AB  - Although animal-borne accelerometers are effective tools for quantifying the
      kinematics of animal behaviors, quantifying the burst movements of small and
      agile aquatic animals remains challenging. To capture the details of burst
      movements, accelerometers need to sample at a very high frequency, which will
      inevitably shorten the recording duration or increase the device size. To
      overcome this problem, we developed a high-frequency acceleration data-logger
      that can be triggered by a manually defined acceleration threshold, thus allowing
      the selective measurement of burst movements. We conducted experiments under
      laboratory and field conditions to examine the performance of the logger. The
      laboratory experiment using red seabream (Pagrus major) showed that the new
      logger could measure the kinematics of their escape behaviors. The field
      experiment using free-swimming yellowtail kingfish (Seriola lalandi) showed that
      the loggers trigger correctly. We suggest that this new logger can be applied to
      measure the burst movements of various small and agile animals.

PMID- 29444850
TI  - Neurovascular dysfunction in dementia - human cellular models and molecular
      mechanisms.
AB  - From the earliest stages of development, when cerebral angiogenesis and
      neurogenesis are entwined, to the end of life, the interplay between vascular and
      neural systems of the brain is critical in health and disease. Cerebral
      microvascular endothelial cells constitute the blood-brain barrier and in concert
      with pericytes or smooth muscle cells, glia and neurons, integrate into a
      functional neurovascular unit (NVU). This multicellular NVU maintains
      homoeostasis of the brain's microenvironment by restricting the entry of systemic
      pathogens and neurotoxins as well as meeting the metabolic demands of neural
      activity. Recent evidence of cerebral microvascular pathologies in vascular
      diseases and dementia, including Alzheimer's disease, has challenged the notion
      that vascular events are merely the consequence of neuronal pathology. This
      review focuses on molecular mechanisms of neurovascular dysfunction in dementia
      and outlines currently employed in vitro models to decode such mechanisms.
      Deciphering neurovascular crosstalk is likely to be more important in
      understanding the molecular mechanisms of disease than previously anticipated and
      may offer novel therapeutic opportunities for dementia and related conditions.

PMID- 29444849
TI  - Amplification of PIP3 signalling by macropinocytic cups.
AB  - In a role distinct from and perhaps more ancient than that in signal
      transduction, PIP3 and Ras help to spatially organize the actin cytoskeleton into
      macropinocytic cups. These large endocytic structures are extended by actin
      polymerization from the cell surface and have at their core an intense patch of
      active Ras and PIP3, around which actin polymerizes, creating cup-shaped
      projections. We hypothesize that active Ras and PIP3 self-amplify within
      macropinocytic cups, in a way that depends on the structural integrity of the
      cup. Signalling that triggers macropinocytosis may therefore be amplified
      downstream in a way that depends on macropinocytosis. This argument provides a
      context for recent findings that signalling to Akt (an effector of PIP3) is
      sensitive to cytoskeletal and macropinocytic inhibitors.

PMID- 29444851
TI  - Inner Workings: How the butterfly got its spots (and why it matters).

PMID- 29444853
TI  - Interprofessional Teamwork Innovation Model (ITIM) to promote communication and
      patient-centred, coordinated care.
AB  - BACKGROUND: Despite recommendations and the need to accelerate redesign of
      delivery models to be team-based and patient-centred, professional silos and
      cultural and structural barriers that inhibit working together and communicating
      effectively still predominate in the hospital setting. Aiming to improve team
      based rounding, we developed, implemented and evaluated the Interprofessional
      Teamwork Innovation Model (ITIM). METHODS: This quality improvement (QI) study
      was conducted at an academic medical centre. We followed the system's QI
      framework, FOCUS-PDSA, with Lean as guiding principles. Primary outcomes included
      30-day all-cause same-hospital readmissions and 30-day emergency department (ED)
      visits. The intervention group consisted of patients receiving care on two
      hospitalist ITIM teams, and patients receiving care from other hospitalist teams
      were matched with a control group. Outcomes were assessed using difference-in
      difference analysis. RESULTS: Team members reported enhanced communication and
      overall time savings. In multivariate modelling, patients discharged from
      hospitalist teams using the ITIM approach were associated with reduced 30-day
      same-hospital readmissions with an estimated point OR of 0.56 (95% CI 0.34 to
      0.92), but there was no impact on 30-day same-hospital ED visits. Difference-in
      difference analysis showed that ITIM was not associated with changes in average
      total direct costs nor average cost per patient day, after adjusting for all
      other covariates in the models, despite the addition of staff resources in the
      ITIM model. CONCLUSION: The ITIM approach facilitates a collaborative environment
      in which patients and their family caregivers, physicians, nurses, pharmacists,
      case managers and others work and share in the process of care.

PMID- 29444854
TI  - BET bromodomain proteins regulate enhancer function during adipogenesis.
AB  - Developmental transitions are guided by master regulatory transcription factors.
      During adipogenesis, a transcriptional cascade culminates in the expression of
      PPARgamma and C/EBPalpha, which orchestrate activation of the adipocyte gene
      expression program. However, the coactivators controlling PPARgamma and
      C/EBPalpha expression are less well characterized. Here, we show the bromodomain
      containing protein, BRD4, regulates transcription of PPARgamma and C/EBPalpha.
      Analysis of BRD4 chromatin occupancy reveals that induction of adipogenesis in
      3T3L1 fibroblasts provokes dynamic redistribution of BRD4 to de novo super
      enhancers proximal to genes controlling adipocyte differentiation. Inhibition of
      the bromodomain and extraterminal domain (BET) family of bromodomain-containing
      proteins impedes BRD4 occupancy at these de novo enhancers and disrupts
      transcription of Pparg and Cebpa, thereby blocking adipogenesis. Furthermore,
      silencing of these BRD4-occupied distal regulatory elements at the Pparg locus by
      CRISPRi demonstrates a critical role for these enhancers in the control of Pparg
      gene expression and adipogenesis in 3T3L1s. Together, these data establish BET
      bromodomain proteins as time- and context-dependent coactivators of the adipocyte
      cell state transition.

PMID- 29444855
TI  - Role of glutathione metabolism in host defense against Borrelia burgdorferi
      infection.
AB  - Pathogen-induced changes in host cell metabolism are known to be important for
      the immune response. In this study, we investigated how infection with the Lyme
      disease-causing bacterium Borrelia burgdorferi (Bb) affects host metabolic
      pathways and how these metabolic pathways may impact host defense. First,
      metabolome analysis was performed on human primary monocytes from healthy
      volunteers, stimulated for 24 h with Bb at low multiplicity of infection (MOI).
      Pathway analysis indicated that glutathione (GSH) metabolism was the pathway most
      significantly affected by Bb Specifically, intracellular levels of GSH increased
      on average 10-fold in response to Bb exposure. Furthermore, these changes were
      found to be specific, as they were not seen during stimulation with other
      pathogens. Next, metabolome analysis was performed on serum samples from patients
      with early-onset Lyme disease in comparison with patients with other infections.
      Supporting the in vitro analysis, we identified a cluster of GSH-related
      metabolites, the gamma-glutamyl amino acids, specifically altered in patients
      with Lyme disease, and not in other infections. Lastly, we performed in vitro
      experiments to validate the role for GSH metabolism in host response against Bb.
      We found that the GSH pathway is essential for Bb-induced cytokine production and
      identified glutathionylation as a potential mediating mechanism. Taken together,
      these data indicate a central role for the GSH pathway in the host response to Bb
      GSH metabolism and glutathionylation may therefore be important factors in the
      pathogenesis of Lyme disease and potentially other inflammatory diseases as well.

PMID- 29444856
TI  - Placental physiology monitored by hyperpolarized dynamic 13C magnetic resonance.
AB  - Placental functions, including transport and metabolism, play essential roles in
      pregnancy. This study assesses such processes in vivo, from a hyperpolarized MRI
      perspective. Hyperpolarized urea, bicarbonate, and pyruvate were administered to
      near-term pregnant rats, and all metabolites displayed distinctive behaviors.
      Little evidence of placental barrier crossing was observed for bicarbonate, at
      least within the timescales allowed by 13C relaxation. By contrast, urea was
      observed to cross the placental barrier, with signatures visible from certain
      fetal organs including the liver. This was further evidenced by the slower decay
      times observed for urea in placentas vis-a-vis other maternal compartments and
      validated by mass spectrometric analyses. A clear placental localization, as well
      as concurrent generation of hyperpolarized lactate, could also be detected for [1
      13C]pyruvate. These metabolites also exhibited longer lifetimes in the placentas
      than in maternal arteries, consistent with a metabolic activity occurring past
      the trophoblastic interface. When extended to a model involving the
      administration of a preeclampsia-causing chemical, hyperpolarized MR revealed
      changes in urea's transport, as well as decreases in placental glycolysis vs. the
      naive animals. These distinct behaviors highlight the potential of hyperpolarized
      MR for the early, minimally invasive detection of aberrant placental metabolism.

PMID- 29444857
TI  - Doubly hybrid density functionals that correctly describe both density and energy
      for atoms.
AB  - Recently, it was argued [Medvedev MG, et al. (2017) Science 355:49-52] that the
      development of density functional approximations (DFAs) is "straying from the
      path toward the exact functional." The exact functional should yield both exact
      energy and density for a system of interest; nevertheless, they found that many
      heavily fitted functionals for molecular energies actually lead to poor electron
      densities of atoms. They also observed a trend that, for the nonempirical and few
      parameter functionals, densities can be improved as one climbs up the first four
      rungs of the Jacob's ladder of DFAs. The XYG3 type of doubly hybrid functionals
      (xDHs) represents a less-empirical and fewer-parameter functional on the top
      fifth rung, in which both the Hartree-Fock-like exchange and the second-order
      perturbative (MP2-like) correlation are hybridized with the low rung functionals.
      Here, we show that xDHs can well describe both density and energy for the same
      atomic set of Medvedev et al., showing that the latter trend can well be extended
      to the top fifth rung.

PMID- 29444858
TI  - Antibiotic killing through oxidized nucleotides.

PMID- 29444859
TI  - Effective games and the confusion over spatial structure.

PMID- 29444860
TI  - Humans quickly learn to blink strategically in response to environmental task
      demands.
AB  - Eye blinking is one of the most frequent human actions. The control of blinking
      is thought to reflect complex interactions between maintaining clear and healthy
      vision and influences tied to central dopaminergic functions including cognitive
      states, psychological factors, and medical conditions. The most imminent
      consequence of blinking is a temporary loss of vision. Minimizing this loss of
      information is a prominent explanation for changes in blink rates and temporarily
      suppressed blinks, but quantifying this loss is difficult, as environmental
      regularities are usually complex and unknown. Here we used a controlled detection
      experiment with parametrically generated event statistics to investigate human
      blinking control. Subjects were able to learn environmental regularities and
      adapted their blinking behavior strategically to better detect future events.
      Crucially, our design enabled us to develop a computational model that allows
      quantifying the consequence of blinking in terms of task performance. The model
      formalizes ideas from active perception by describing blinking in terms of
      optimal control in trading off intrinsic costs for blink suppression with task
      related costs for missing an event under perceptual uncertainty. Remarkably, this
      model not only is sufficient to reproduce key characteristics of the observed
      blinking behavior such as blink suppression and blink compensation but also
      predicts without further assumptions the well-known and diverse distributions of
      time intervals between blinks, for which an explanation has long been elusive.

PMID- 29444863
TI  - Capturing bovine pluripotency.

PMID- 29444862
TI  - Targeted DNA demethylation of the Arabidopsis genome using the human TET1
      catalytic domain.
AB  - DNA methylation is an important epigenetic modification involved in gene
      regulation and transposable element silencing. Changes in DNA methylation can be
      heritable and, thus, can lead to the formation of stable epialleles. A well
      characterized example of a stable epiallele in plants is fwa, which consists of
      the loss of DNA cytosine methylation (5mC) in the promoter of the FLOWERING
      WAGENINGEN (FWA) gene, causing up-regulation of FWA and a heritable late
      flowering phenotype. Here we demonstrate that a fusion between the catalytic
      domain of the human demethylase TEN-ELEVEN TRANSLOCATION1 (TET1cd) and an
      artificial zinc finger (ZF) designed to target the FWA promoter can cause highly
      efficient targeted demethylation, FWA up-regulation, and a heritable late
      flowering phenotype. Additional ZF-TET1cd fusions designed to target methylated
      regions of the CACTA1 transposon also caused targeted demethylation and changes
      in expression. Finally, we have developed a CRISPR/dCas9-based targeted
      demethylation system using the TET1cd and a modified SunTag system. Similar to
      the ZF-TET1cd fusions, the SunTag-TET1cd system is able to target demethylation
      and activate gene expression when directed to the FWA or CACTA1 loci. Our study
      provides tools for targeted removal of 5mC at specific loci in the genome with
      high specificity and minimal off-target effects. These tools provide the
      opportunity to develop new epialleles for traits of interest, and to reactivate
      expression of previously silenced genes, transgenes, or transposons.

PMID- 29444861
TI  - Interacting-heads motif has been conserved as a mechanism of myosin II inhibition
      since before the origin of animals.
AB  - Electron microscope studies have shown that the switched-off state of myosin II
      in muscle involves intramolecular interaction between the two heads of myosin and
      between one head and the tail. The interaction, seen in both myosin filaments and
      isolated molecules, inhibits activity by blocking actin-binding and ATPase sites
      on myosin. This interacting-heads motif is highly conserved, occurring in
      invertebrates and vertebrates, in striated, smooth, and nonmuscle myosin IIs, and
      in myosins regulated by both Ca2+ binding and regulatory light-chain
      phosphorylation. Our goal was to determine how early this motif arose by studying
      the structure of inhibited myosin II molecules from primitive animals and from
      earlier, unicellular species that predate animals. Myosin II from Cnidaria (sea
      anemones, jellyfish), the most primitive animals with muscles, and Porifera
      (sponges), the most primitive of all animals (lacking muscle tissue) showed the
      same interacting-heads structure as myosins from higher animals, confirming the
      early origin of the motif. The social amoeba Dictyostelium discoideum showed a
      similar, but modified, version of the motif, while the amoeba Acanthamoeba
      castellanii and fission yeast (Schizosaccharomyces pombe) showed no head-head
      interaction, consistent with the different sequences and regulatory mechanisms of
      these myosins compared with animal myosin IIs. Our results suggest that head
      head/head-tail interactions have been conserved, with slight modifications, as a
      mechanism for regulating myosin II activity from the emergence of the first
      animals and before. The early origins of these interactions highlight their
      importance in generating the inhibited (relaxed) state of myosin in muscle and
      nonmuscle cells.

PMID- 29444865
TI  - MLL-AF4, a double-edged sword for iPSC respecification into HSPCs.

PMID- 29444864
TI  - Lineage-specific gene acquisition or loss is involved in interspecific hybrid
      sterility in rice.
AB  - Understanding the genetic basis of reproductive barriers between species has been
      a central issue in evolutionary biology. The S1 locus in rice causes hybrid
      sterility and is a major reproductive barrier between two rice species, Oryza
      sativa and Oryza glaberrima The O. glaberrima-derived allele (denoted S1g) on the
      S1 locus causes preferential abortion of gametes with its allelic alternative
      (denoted S1s) in S1g/S1s heterozygotes. Here, we used mutagenesis and screening
      of fertile hybrid plants to isolate a mutant with an allele, S1mut, which does
      not confer sterility in the S1mut/S1g and S1mut/S1s hybrids. We found that the
      causal mutation of the S1mut allele was a deletion in the peptidase-coding gene
      (denoted "SSP") in the S1 locus of O. glaberrima No orthologous genes of SSP were
      found in the O. sativa genome. Transformation experiments indicated that the
      introduction of SSP in carriers of the S1s allele did not induce sterility. In
      S1mut/S1s heterozygotes, the insertion of SSP led to sterility, suggesting that
      SSP complemented the loss of the functional phenotype of the mutant and that
      multiple factors are involved in the phenomenon. The polymorphisms caused by the
      lineage-specific acquisition or loss of the SSP gene were implicated in the
      generation of hybrid sterility. Our results demonstrated that artificial
      disruption of a single gene for the reproductive barrier creates a "neutral"
      allele, which facilitates interspecific hybridization for breeding programs.

PMID- 29444866
TI  - Long-term value memory in primates.

PMID- 29444868
TI  - NHS urgently needs clarity on EU staff rights post-Brexit, say senior doctors.

PMID- 29444869
TI  - Effective screening leads to better outcomes in sickle cell disease.

PMID- 29444870
TI  - Canada makes deal to reduce generic drug prices.

PMID- 29444867
TI  - Evolutionary stability of antibiotic protection in a defensive symbiosis.
AB  - The increasing resistance of human pathogens severely limits the efficacy of
      antibiotics in medicine, yet many animals, including solitary beewolf wasps,
      successfully engage in defensive alliances with antibiotic-producing bacteria for
      millions of years. Here, we report on the in situ production of 49 derivatives
      belonging to three antibiotic compound classes (45 piericidin derivatives, 3
      streptochlorin derivatives, and nigericin) by the symbionts of 25 beewolf host
      species and subspecies, spanning 68 million years of evolution. Despite a high
      degree of qualitative stability in the antibiotic mixture, we found consistent
      quantitative differences between species and across geographic localities,
      presumably reflecting adaptations to combat local pathogen communities.
      Antimicrobial bioassays with the three main components and in silico predictions
      based on the structure and specificity in polyketide synthase domains of the
      piericidin biosynthesis gene cluster yield insights into the mechanistic basis
      and ecoevolutionary implications of producing a complex mixture of antimicrobial
      compounds in a natural setting.

PMID- 29444871
TI  - Doctors and parents agree care plan for toddler with terminal condition.

PMID- 29444874
TI  - Research in health policy making in China: out-of-pocket payments in Healthy
      China 2030.

PMID- 29444873
TI  - Hypoxia-inducible KDM3A addiction in multiple myeloma.
AB  - In multiple myeloma (MM), the bone marrow (BM) microenvironment may contain a
      myeloma cell fraction that has acquired treatment resistance by undergoing an
      epigenetic gene expression change. Hypoxic stress is an important factor in the
      BM microenvironment. Recently, we demonstrated that miR-210 was upregulated in
      hypoxia and downregulated IRF4, which is known as an essential factor in myeloma
      oncogenesis in normoxia. In the study, we demonstrated that myeloma cells still
      showed a strong antiapoptotic phenotype despite IRF4 downregulation, suggesting
      that another antiapoptotic factor might be involved under hypoxic stress. To
      determine the factor or factors, we conducted gene expression analysis on myeloma
      cells (primary samples and cell lines) that were exposed to chronic hypoxia and
      observed upregulation of glycolytic genes and genes encoding H3K9 demethylases in
      myeloma cells with hypoxia. Among these, KDM3A was most significantly upregulated
      in all examined cells, and its knockdown induced apoptosis of myeloma cells in
      chronic hypoxia. Expression of KDM3A was dependent on HIF-1alpha, which is a
      transcription factor specifically upregulated in hypoxia. We further demonstrated
      that an essential target of KDM3A was a noncoding gene, MALAT1, whose
      upregulation contributed to acquisition of an antiapoptotic phenotype by
      accumulation of HIF-1alpha, leading to upregulation of glycolytic genes under
      hypoxia. This process was independent from IRF4. These results led us to conclude
      that the hypoxia-inducible HIF-1alpha-KDM3A-MALAT1 axis also contributes to
      acquisition of the antiapoptotic phenotype via upregulation of glycolysis
      promoting genes. Thus, this axis is a promising therapeutic target against
      myeloma cells in the BM microenvironment.

PMID- 29444875
TI  - GP inspections: are sanctions holding back improvement in poor areas?

PMID- 29444872
TI  - FVIII proteins with a modified immunodominant T-cell epitope exhibit reduced
      immunogenicity and normal FVIII activity.
AB  - Factor VIII (FVIII)-neutralizing antibodies (inhibitors) are a serious
      complication in hemophilia A (HA). The peptide FVIII2194-2213 contains an
      immunodominant HLA-DRA*01-DRB1*01:01 (DRB1*01:01)-restricted epitope recognized
      by CD4+ T-effector cells from HA subjects. The aim of this study was to identify
      amino acid substitutions to deimmunize this epitope while retaining procoagulant
      function and expression levels comparable to those of wild-type (WT) FVIII
      proteins. The shortest DRB1*01:01-binding peptide was FVIII2194-2205, and
      residues important for affinity were identified as F2196, M2199, A2201, and
      S2204. T-cell proliferation experiments with Ala-substituted FVIII2194-2205
      peptides identified F2196A as a substitution that abrogated proliferation of
      clones specific for the WT sequence. T-cell clones that were stimulated by
      recombinant WT-FVIII-C2 (rWT-FVIII-C2) protein did not proliferate when cultured
      with rFVIII-C2-F2196A, indicating the immunogenic peptide includes a naturally
      processed T-cell epitope. Additional amino acid substitutions at F2196 and M2199
      were evaluated by peptide-MHC class II (MHCII)-binding assays, T-cell
      proliferation assays, epitope prediction algorithms, and sequence homologies. Six
      B-domain-deleted (BDD)-FVIII proteins with substitutions F2196A, F2196L, F2196K,
      M2199A, M2199W, or M2199R were produced. Proliferation of T-cell clones and
      polyclonal lines in response to rBDD-FVIII-F2196K and rBDD-FVIII-M2199A was
      reduced compared with responses to WT-BDD-FVIII. The BDD-FVIII-F2196K sequence
      modification appears to be the most promising sequence variant tested here, due
      to its effectiveness at eliminating DRB1*01:01-restricted immunogenicity, low
      potential immunogenicity in the context of other MHCII alleles, expression level
      comparable to WT-BDD-FVIII, and retained procoagulant activity. These results
      provide proof of principle for the design of less immunogenic FVIII proteins
      targeted to specific subsets of HA patients.

PMID- 29444876
TI  - Electronic fetal heart rate monitoring: we need new research approaches.

PMID- 29444877
TI  - Practices in poor areas are more likely to face CQC sanctions.

PMID- 29444878
TI  - Tackling hearing loss to improve the care of older adults.

PMID- 29444879
TI  - A play on mental illness.

PMID- 29444880
TI  - CDC tightens controls on scientists' communication with news media.

PMID- 29444882
TI  - Appointment day-the tip of an iceberg.

PMID- 29444881
TI  - Ischaemic stroke, haemorrhage, and mortality in older patients with chronic
      kidney disease newly started on anticoagulation for atrial fibrillation: a
      population based study from UK primary care.
AB  - OBJECTIVE: To assess the association between anticoagulation, ischaemic stroke,
      gastrointestinal and cerebral haemorrhage, and all cause mortality in older
      people with atrial fibrillation and chronic kidney disease. DESIGN: Propensity
      matched, population based, retrospective cohort analysis from January 2006
      through December 2016. SETTING: The Royal College of General Practitioners
      Research and Surveillance Centre database population of almost 2.73 million
      patients from 110 general practices across England and Wales. PARTICIPANTS:
      Patients aged 65 years and over with a new diagnosis of atrial fibrillation and
      estimated glomerular filtration rate (eGFR) of <50 mL/min/1.73m2, calculated
      using the chronic kidney disease epidemiology collaboration creatinine equation.
      Patients with a previous diagnosis of atrial fibrillation or receiving
      anticoagulation in the preceding 120 days were excluded, as were patients
      requiring dialysis and recipients of renal transplants. INTERVENTION: Receipt of
      an anticoagulant prescription within 60 days of atrial fibrillation diagnosis.
      MAIN OUTCOME MEASURES: Ischaemic stroke, cerebral or gastrointestinal
      haemorrhage, and all cause mortality. RESULTS: 6977 patients with chronic kidney
      disease and newly diagnosed atrial fibrillation were identified, of whom 2434
      were on anticoagulants within 60 days of diagnosis and 4543 were not. 2434 pairs
      were matched using propensity scores by exposure to anticoagulant or none and
      followed for a median of 506 days. The crude rates for ischaemic stroke and
      haemorrhage were 4.6 and 1.2 after taking anticoagulants and 1.5 and 0.4 in
      patients who were not taking anticoagulant per 100 person years, respectively.
      The hazard ratios for ischaemic stroke, haemorrhage, and all cause mortality for
      those on anticoagulants were 2.60 (95% confidence interval 2.00 to 3.38), 2.42
      (1.44 to 4.05), and 0.82 (0.74 to 0.91) compared with those who received no
      anticoagulation. CONCLUSION: Giving anticoagulants to older people with
      concomitant atrial fibrillation and chronic kidney disease was associated with an
      increased rate of ischaemic stroke and haemorrhage but a paradoxical lowered rate
      of all cause mortality. Careful consideration should be given before starting
      anticoagulants in older people with chronic kidney disease who develop atrial
      fibrillation. There remains an urgent need for adequately powered randomised
      trials in this population to explore these findings and to provide clarity on
      correct clinical management.

PMID- 29444883
TI  - Sam Guglani: Life, mortality, and poetry.

PMID- 29444884
TI  - Intrapartum cardiotocography and pattern recognition.

PMID- 29444885
TI  - Data sharing in medical research.

PMID- 29444886
TI  - A child with a painless, deformed wrist.

PMID- 29444888
TI  - Trump administration blames foreigners for US's high drug costs.

PMID- 29444887
TI  - Discussing dying: five minutes with Paul Cosford.

PMID- 29444890
TI  - Effect of gestational diabetes and hypertensive disorders of pregnancy on
      postpartum cardiometabolic risk.
AB  - AIMS: The cumulative effect of gestational diabetes mellitus (GDM) and
      hypertensive disorders of pregnancy (HDP) on postpartum cardio-metabolic diseases
      is equivocal. We aimed to assess the associations of GDM and HDP's individual and
      synergic contribution to risks of postpartum cardio-metabolic diseases (metabolic
      syndrome (MetS), abnormal glucose metabolism and hypertension (HTN)). METHODS: Of
      participants from a Singapore birth cohort, 276 mothers attending the 5-year
      postpartum visit were included in this study. During this visit, we collected
      mothers' history of GDM and HDP in all live births in a chronicle sequence and
      assessed the cardio-metabolic risks based on blood pressure, anthropometry and a
      panel of serum biomarkers. We diagnosed MetS, abnormal glucose metabolism and HTN
      according to Adult Treatment Panel III 2000 and World Health Organization
      guidelines. RESULTS: Of 276 mothers, 157 (56.9%) had histories of GDM while 23
      (8.3%) had histories of HDP. After full adjustment, we found associations of GDM
      episodes with postpartum abnormal glucose metabolism (single episode: relative
      risk (RR) 2.9 (95% CI: 1.7, 4.8); recurrent episodes (>=2): RR = 3.8 (2.1-6.8)).
      Also, we found association between histories of HDP and HTN (RR = 3.6 (1.5,
      8.6)). Having either (RR 2.6 (1.7-3.9)) or both gestational complications (RR 2.7
      (1.6-4.9)) was associated with similar risk of postpartum cardio-metabolic
      disease. CONCLUSIONS: Mothers with GDM or HDP had a threefold increased risk of
      postpartum abnormal glucose metabolism or HTN, respectively. Having both GDM and
      HDP during past pregnancies was not associated with additional risk of postpartum
      cardio-metabolic diseases beyond that associated with either complication alone.

PMID- 29444891
TI  - Metabolic Syndrome Is Associated With Impaired Diastolic Function Independently
      of MRI-Derived Myocardial Extracellular Volume: The MESA Study.
AB  - The relationship of metabolic syndrome (MetS) and insulin resistance (one of its
      key pathophysiological mediators) with diastolic dysfunction and myocardial
      fibrosis is not well understood. This study aimed to evaluate the association of
      MetS with diastolic function and myocardial extracellular matrix (ECM) using
      cardiac MRI (CMRI) in a large community-based population. This cross-sectional
      analysis included 1,582 participants from the Multi-Ethnic Study of
      Atherosclerosis (MESA) with left ventricular ejection fraction >=50% and no
      history of cardiac events. Diastolic function was assessed using tagged CMRI
      parameters including end-diastolic strain rate (EDSR) and strain relaxation index
      (SRI). ECM was evaluated using extracellular volume (ECV) quantification.
      Participants' mean age was 67.4 +/- 8.6 years, and 48.1% were males. MetS was
      present in 533 individuals (33.7%), and type 2 diabetes in 250 (15.8%). In the
      multivariable analyses, MetS (irrespective of the presence of type 2 diabetes)
      and higher insulin resistance were associated with impaired diastolic function
      (higher SRI and lower EDSR), independent of ECV. In conclusion, MetS,
      irrespective of the presence of type 2 diabetes, was independently associated
      with impaired diastole. These functional myocardial changes seem to result from
      intrinsic cardiomyocyte alterations, irrespective of the myocardial interstitium
      (including fibrosis).

PMID- 29444892
TI  - Role of Protein Phosphatase 1 and Inhibitor of Protein Phosphatase 1 in Nitric
      Oxide-Dependent Inhibition of the DNA Damage Response in Pancreatic beta-Cells.
AB  - Nitric oxide is produced at micromolar levels by pancreatic beta-cells during
      exposure to proinflammatory cytokines. While classically viewed as damaging,
      nitric oxide also activates pathways that promote beta-cell survival. We have
      shown that nitric oxide, in a cell type-selective manner, inhibits the DNA damage
      response (DDR) and, in doing so, protects beta-cells from DNA damage-induced
      apoptosis. This study explores potential mechanisms by which nitric oxide
      inhibits DDR signaling. We show that inhibition of DDR signaling (measured by
      gammaH2AX formation and the phosphorylation of KAP1) is selective for nitric
      oxide, as other forms of reactive oxygen/nitrogen species do not impair DDR
      signaling. The kinetics and broad range of DDR substrates that are inhibited
      suggest that protein phosphatase activation may be one mechanism by which nitric
      oxide attenuates DDR signaling in beta-cells. While protein phosphatase 1 (PP1)
      is a primary regulator of DDR signaling and an inhibitor of PP1 (IPP1) is
      selectively expressed only in beta-cells, disruption of either IPP1 or PP1 does
      not modify the inhibitory actions of nitric oxide on DDR signaling in beta-cells.
      These findings support a PP1-independent mechanism by which nitric oxide
      selectively impairs DDR signaling and protects beta-cells from DNA damage-induced
      apoptosis.

PMID- 29444893
TI  - Dusp6 attenuates Ras/MAPK signaling to limit zebrafish heart regeneration.
AB  - Zebrafish regenerate cardiac tissue through proliferation of pre-existing
      cardiomyocytes and neovascularization. Secreted growth factors such as FGFs, IGF,
      PDGFs and Neuregulin play essential roles in stimulating cardiomyocyte
      proliferation. These factors activate the Ras/MAPK pathway, which is tightly
      controlled by the feedback attenuator Dual specificity phosphatase 6 (Dusp6), an
      ERK phosphatase. Here, we show that suppressing Dusp6 function enhances cardiac
      regeneration. Inactivation of Dusp6 by small molecules or by gene inactivation
      increased cardiomyocyte proliferation, coronary angiogenesis, and reduced
      fibrosis after ventricular resection. Inhibition of Erbb or PDGF receptor
      signaling suppressed cardiac regeneration in wild-type zebrafish, but had a
      milder effect on regeneration in dusp6 mutants. Moreover, in rat primary
      cardiomyocytes, NRG1-stimulated proliferation can be enhanced upon chemical
      inhibition of Dusp6 with BCI. Our results suggest that Dusp6 attenuates Ras/MAPK
      signaling during regeneration and that suppressing Dusp6 can enhance cardiac
      repair.

PMID- 29444894
TI  - Morphometrics of complex cell shapes: lobe contribution elliptic Fourier analysis
      (LOCO-EFA).
AB  - Quantifying cell morphology is fundamental to the statistical study of cell
      populations, and can help unravel mechanisms underlying cell and tissue
      morphogenesis. Current methods, however, require extensive human intervention,
      are highly parameter sensitive, or produce metrics that are difficult to
      interpret biologically. We therefore developed a method, lobe contribution
      elliptical Fourier analysis (LOCO-EFA), which generates from digitalised two
      dimensional cell outlines meaningful descriptors that can be directly matched to
      morphological features. This is shown by studying well-defined geometric shapes
      as well as actual biological cells from plant and animal tissues. LOCO-EFA
      provides a tool to phenotype efficiently and objectively populations of cells,
      here demonstrated by applying it to the complex shaped pavement cells of
      Arabidopsis thaliana wild-type and speechless leaves, and Drosophila amnioserosa
      cells. To validate our method's applicability to large populations, we analysed
      computer-generated tissues. By controlling in silico cell shape, we explored the
      potential impact of cell packing on individual cell shape, quantifying through
      LOCO-EFA deviations between the specified shape of single cells in isolation and
      the resultant shape when they interact within a confluent tissue.

PMID- 29444895
TI  - Optimizing Hybrid Closed-Loop Therapy in Adolescents and Emerging Adults Using
      the MiniMed 670G System.
AB  - OBJECTIVE: The MiniMed 670G System is the first commercial hybrid closed-loop
      (HCL) system for management of type 1 diabetes. Using data from adolescent and
      young adult participants, we compared insulin delivery patterns and time-in-range
      metrics in HCL (Auto Mode) and open loop (OL). System alerts, usage profiles, and
      operational parameters were examined to provide suggestions for optimal clinical
      use of the system. RESEARCH DESIGN AND METHODS: Data from 31 adolescent and young
      adult participants (14-26 years old) at three clinical sites in the 670G pivotal
      trial were analyzed. Participants had a 2-week run-in period in OL, followed by a
      3-month in-home study phase with HCL functionality enabled. Data were compared
      between baseline OL and HCL use after 1 week, 1 month, 2 months, and 3 months.
      RESULTS: Carbohydrate-to-insulin (C-to-I) ratios were more aggressive for all
      meals with HCL compared with baseline OL. Total daily insulin dose and basal-to
      bolus ratio did not change during the trial. Time in range increased 14% with use
      of Auto Mode after 3 months (P < 0.001), and HbA1c decreased 0.75%. Auto Mode
      exits were primarily due to sensor/insulin delivery alerts and hyperglycemia. The
      percentage of time in Auto Mode gradually declined from 87%, with a final use
      rate of 72% (-15%). CONCLUSIONS: In transitioning young patients to the 670G
      system, providers should anticipate immediate C-to-I ratio adjustments while also
      assessing active insulin time. Users should anticipate occasional Auto Mode
      exits, which can be reduced by following system instructions and reliably
      bolusing for meals. Unique 670G system functionality requires ongoing clinical
      guidance and education from providers.

PMID- 29444896
TI  - Regulation of Hed1 and Rad54 binding during maturation of the meiosis-specific
      presynaptic complex.
AB  - Most eukaryotes have two Rad51/RecA family recombinases, Rad51, which promotes
      recombination during mitotic double-strand break (DSB) repair, and the meiosis
      specific recombinase Dmc1. During meiosis, the strand exchange activity of Rad51
      is downregulated through interactions with the meiosis-specific protein Hed1,
      which helps ensure that strand exchange is driven by Dmc1 instead of Rad51. Hed1
      acts by preventing Rad51 from interacting with Rad54, a cofactor required for
      promoting strand exchange during homologous recombination. However, we have a
      poor quantitative understanding of the regulatory interplay between these
      proteins. Here, we use real-time single-molecule imaging to probe how the Hed1-
      and Rad54-mediated regulatory network contributes to the identity of mitotic and
      meiotic presynaptic complexes. Based on our findings, we define a model in which
      kinetic competition between Hed1 and Rad54 helps define the functional identity
      of the presynaptic complex as cells undergo the transition from mitotic to
      meiotic repair.

PMID- 29444897
TI  - Role of NKp46+ natural killer cells in house dust mite-driven asthma.
AB  - House dust mite (HDM)-allergic asthma is driven by T helper 2 (Th2) lymphocytes,
      but also innate immune cells control key aspects of the disease. The precise
      function of innate natural killer (NK) cells during the initiation and
      propagation of asthma has been very confusing, in part because different, not
      entirely specific, strategies were used to target these cells. We show that HDM
      inhalation rapidly led to the accumulation of NK cells in the lung-draining lymph
      nodes and of activated CD69+ NK cells in the bronchoalveolar lumen. However,
      genetically engineered Ncr1-DTA or Ncr1-DTR mice that constitutively or
      temporarily lack NK cells, still developed all key features of acute or chronic
      HDM-driven asthma, such as bronchial hyperreactivity, Th2 cytokine production,
      eosinophilia, mucus overproduction, and Th2-dependent immunoglobulin serum
      titers. The same results were obtained by administration of conventional NK1.1 or
      asialo-GM1 NK cell-depleting antibodies, antibody-mediated blocking of the NKG2D
      receptor, or genetic NKG2D deficiency. Thus, although NK cells accumulate in
      allergen-challenged lungs, our findings comprehensively demonstrate that these
      cells are not required for HDM-driven asthma in the mouse.

PMID- 29444898
TI  - Significant prevalence of NR3C1 mutations in incidentally discovered bilateral
      adrenal hyperplasia: results of the French MUTA-GR Study.
AB  - BACKGROUND: Recently discovered mutations of NR3C1 gene, encoding for the GR, in
      patients with glucocorticoid resistance and bilateral adrenal incidentalomas
      prompted us to investigate whether GR mutations might be associated with adrenal
      hyperplasia. OBJECTIVE: The multicenter French Clinical Research Program (Muta
      GR) was set up to determine the prevalence of GR mutations and polymorphisms in
      patients harboring bilateral adrenal incidentalomas associated with hypertension
      and/or biological hypercortisolism without clinical Cushing's signs. RESULTS: One
      hundred patients were included in whom NR3C1 sequencing revealed five original
      heterozygous GR mutations that impaired GR signaling in vitro. Mutated patients
      presented with mild glucocorticoid resistance defined as elevated urinary free
      cortisol (1.7 +/- 0.7 vs 0.9 +/- 0.8 upper limit of normal range, P = 0.006),
      incomplete 1 mg dexamethasone suppression test without suppressed 8-AM
      adrenocorticotrophin levels (30.9 +/- 31.2 vs 16.2 +/- 17.5 pg/mL) compared to
      the non-mutated patients. Potassium and aldosterone levels were lower in mutated
      patients (3.6 +/- 0.2 vs 4.1 +/- 0.5 mmol/L, P = 0.01, and 17.3 +/- 9.9 vs 98.6
      +/- 115.4 pg/mL, P = 0.0011, respectively) without elevated renin levels,
      consistent with pseudohypermineralocorticism. Ex vivo characterization of mutated
      patients' fibroblasts demonstrated GR haploinsufficiency as revealed by below
      normal glucocorticoid induction of FKBP5 gene expression. There was no
      association between GR polymorphisms and adrenal hyperplasia in this cohort,
      except an over-representation of BclI polymorphism. CONCLUSION: The 5% prevalence
      of heterozygous NR3C1 mutations discovered in our series is higher than initially
      thought and encourages GR mutation screening in patients with adrenal
      incidentalomas to unambiguously differentiate from Cushing's states and to
      optimize personalized follow-up.

PMID- 29444899
TI  - Comparison of Glasgow Admission Prediction Score and Amb Score in predicting need
      for inpatient care.
AB  - AIM: We compared the abilities of two established clinical scores to predict
      emergency department (ED) disposition: the Glasgow Admission Prediction Score
      (GAPS) and the Ambulatory Score (Ambs). METHODS: The scores were compared in a
      prospective, multicentre cohort study. We recruited consecutive patients
      attending ED triage at two UK sites: Northern General Hospital in Sheffield and
      Glasgow Royal Infirmary, between February and May 2016. Each had a GAPS and Ambs
      calculated at the time of triage, with the triage nurses and treating clinicians
      blinded to the scores. Patients were followed up to hospital discharge. The
      ability of the scores to discriminate discharge from ED and from hospital at 12
      and 48 hours after arrival was compared using the area under the curve (AUC) of
      their receiving-operator characteristics (ROC). RESULTS: 1424 triage attendances
      were suitable for analysis during the study period, of which 567 (39.8%) were
      admitted. The AUC for predicting admission was significantly higher for GAPS at
      0.807 (95% CI 0.785 to 0.830), compared with 0.743 (95% CI 0.717 to 0.769) for
      Ambs, P<0.00001. Similar results were seen when comparing ability to predict
      hospital stay of >12 hour and >48 hour. GAPS was also more accurate as a binary
      test, correctly predicting 1057 outcomes compared with 1004 for Ambs
      (74.2vs70.5%, P=0.012). CONCLUSION: The GAPS is a significantly better predictor
      of need for hospital admission than Ambs in an unselected ED population.

PMID- 29444901
TI  - Intensive Hemodialysis Fails to Reduce Plasma Levels of Uremic Solutes.

PMID- 29444900
TI  - Extended Duration Nocturnal Hemodialysis and Changes in Plasma Metabolite
      Profiles.
AB  - BACKGROUND AND OBJECTIVES: In-center, extended duration nocturnal hemodialysis
      has been associated with variable clinical benefits, but the effect of extended
      duration hemodialysis on many established uremic solutes and other components of
      the metabolome is unknown. We determined the magnitude of change in metabolite
      profiles for patients on extended duration nocturnal hemodialysis. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: In a 52-week prospective, observational
      study, we followed 33 patients receiving conventional thrice weekly hemodialysis
      who converted to nocturnal hemodialysis (7-8 hours per session, three times per
      week). A separate group of 20 patients who remained on conventional hemodialysis
      (3-4 hours per session, three times per week) served as a control group. For both
      groups, we applied liquid chromatography-mass spectrometry-based metabolite
      profiling on stored plasma samples collected from all participants at baseline
      and after 1 year. We examined longitudinal changes in 164 metabolites among those
      who remained on conventional hemodialysis and those who converted to nocturnal
      hemodialysis using Wilcoxon rank sum tests adjusted for multiple comparisons
      (false discovery rate <0.05). RESULTS: On average, the nocturnal group had 9.6
      hours more dialysis per week than the conventional group. Among 164 metabolites,
      none changed significantly from baseline to study end in the conventional group.
      Twenty-nine metabolites changed in the nocturnal group, 21 of which increased
      from baseline to study end (including all branched-chain amino acids). Eight
      metabolites decreased after conversion to nocturnal dialysis, including l
      carnitine and acetylcarnitine. By contrast, several established uremic retention
      solutes, including p-cresol sulfate, indoxyl sulfate, and trimethylamine N-oxide,
      did not change with extended dialysis. CONCLUSIONS: Across a wide array of
      metabolites examined, extended duration hemodialysis was associated with modest
      changes in the plasma metabolome, with most differences relating to metabolite
      increases, despite increased dialysis time. Few metabolites showed reduction with
      more dialysis, and no change in several established uremic toxins was observed.

PMID- 29444902
TI  - The Effect of Single Mismatches on Primer Extension.
AB  - BACKGROUND: Allele-specific PCR is an important diagnostic tool that identifies
      single-nucleotide variants by preferential amplification of a particular allele,
      using primers that are mismatched to all but one allele variant. METHODS: We
      applied a fluorescent stopped-flow polymerase assay to measure extension rates
      from oligonucleotide hairpins to simulate primer-template pairs. Under PCR
      applicable conditions, reaction rates were recorded in nucleotides per second per
      polymerase (nt/s/poly). The effects of temperature, potassium chloride, mismatch
      type, and position were studied with primarily a deletion mutant of Thermus
      aquaticus (Taq) DNA polymerase and 135 oligonucleotide sequences. RESULTS: Rates
      at 65  degrees C were between 205 +/- 11 and 177 +/- 8 nt/s/poly for matched
      templates and between 4.55 +/- 0.21 and 0.008 +/- 0.005 nt/s/poly for 3'
      mismatched templates. Although extension rates progressively increased with
      mismatches further away from the 3' end, rates were still reduced by as much as
      84% with a C . C mismatch 6 bases from the 3' end. The optimal extension
      temperature for matched sequences was 70  degrees C, shifting to 55-60  degrees C
      for 3' mismatches. KCl inhibited mismatch extension. The Michaelis constant (Km)
      was increased and the apparent unimolecular rate constant (kcat) decreased for 3'
      mismatches relative to matched templates. CONCLUSIONS: Although primer extension
      of mismatches depends on mismatch type and position, variation also depends on
      local sequence, KCl concentration, and the type of polymerase. Introduction of 3'
      mismatches reduces the optimal temperature for extension, suggesting higher
      annealing temperatures for better allele discrimination. Quantitative
      descriptions of expected specificity in allele-specific PCR provide additional
      design direction and suggest when other methods (e.g., high-resolution melting
      analysis) may be a better choice.

PMID- 29444903
TI  - Generation and Characterization of a CYP2C11-Null Rat Model by Using the
      CRISPR/Cas9 Method.
AB  - CYP2C11 is involved in the metabolism of many drugs in rats. To assess the roles
      of CYP2C11 in physiology and drug metabolism, a CYP2C11-null rat model was
      generated using the clustered regularly interspaced short palindromic repeats
      (CRISPR)/Cas9method. A 2-base pair insertion was added to exon 6 of CYP2C11 in
      Sprague-Dawley rats. CYP2C11 was not detected by western blotting in liver
      microsomes of CYP2C11-null rats. No off-target effects were found at 11 predicted
      sites of the knockout model. The CYP2C11-null rats were viable and had no obvious
      abnormalities, with the exception of reduced fertility. Puberty in CYP2C11-null
      rats appeared to be delayed by ~20 days, and the average litter size fell by 43%.
      Tolbutamide was used as a probe in this drug metabolism study. In the liver
      microsomes of CYP2C11-null rats, the Vmax and intrinsicclearance values decreased
      by 22% and 47%, respectively, compared with those of wild-type rats. The Km
      values increased by 47% compared with that of wild types. However, our
      pharmacokinetics study showed no major differences in any parameters between the
      two strains, in both males and females. In conclusion, a CYP2C11-null rat model
      was successfully generated and is a valuable tool to study the in vivo function
      of CYP2C11.

PMID- 29444904
TI  - Mutation in an alternative transcript of CDKL5 in a boy with early-onset
      seizures.
AB  - Infantile-onset epilepsies are a set of severe, heterogeneous disorders for which
      clinical genetic testing yields causative mutations in ~20%-50% of affected
      individuals. We report the case of a boy presenting with intractable seizures at
      2 wk of age, for whom gene panel testing was unrevealing. Research-based whole
      genome sequencing of the proband and four unaffected family members identified a
      de novo mutation, NM_001323289.1:c.2828_2829delGA in CDKL5, a gene associated
      with X-linked early infantile epileptic encephalopathy 2. CDKL5 has multiple
      alternative transcripts, and the mutation lies in an exon in the brain-expressed
      forms. The mutation was undetected by gene panel sequencing because of its
      intronic location in the CDKL5 transcript typically used to define the exons of
      this gene for clinical exon-based tests (NM_003159). This is the first report of
      a patient with a mutation in an alternative transcript of CDKL5 This finding
      suggests that incorporating alternative transcripts into the design and variant
      interpretation of exon-based tests, including gene panel and exome sequencing,
      could improve the diagnostic yield.

PMID- 29444906
TI  - Detection of myositis-specific antibodies: additional notes.

PMID- 29444905
TI  - Renal Interstitial Platelet-Derived Growth Factor Receptor-beta Cells Support
      Proximal Tubular Regeneration.
AB  - BACKGROUND: The kidney is considered to be a structurally stable organ with
      limited baseline cellular turnover. Nevertheless, single cells must be constantly
      replaced to conserve the functional integrity of the organ. PDGF chain B (PDGF
      BB) signaling through fibroblast PDGF receptor-beta (PDGFRbeta) contributes to
      interstitial-epithelial cell communication and facilitates regenerative functions
      in several organs. However, the potential role of interstitial cells in renal
      tubular regeneration has not been examined. METHODS: In mice with fluorescent
      protein expression in renal tubular cells and PDGFRbeta-positive interstitial
      cells, we ablated single tubular cells by high laser exposure. We then used
      serial intravital multiphoton microscopy with subsequent three-dimensional
      reconstruction and ex vivo histology to evaluate the cellular and molecular
      processes involved in tubular regeneration. RESULTS: Single-tubular cell ablation
      caused the migration and division of dedifferentiated tubular epithelial cells
      that preceded tubular regeneration. Moreover, tubular cell ablation caused
      immediate calcium responses in adjacent PDGFRbeta-positive interstitial cells and
      the rapid migration thereof toward the injury. These PDGFRbeta-positive cells
      enclosed the injured epithelium before the onset of tubular cell
      dedifferentiation, and the later withdrawal of these PDGFRbeta-positive cells
      correlated with signs of tubular cell redifferentiation. Intraperitoneal
      administration of trapidil to block PDGFRbeta impeded PDGFRbeta-positive cell
      migration to the tubular injury site and compromised the recovery of tubular
      function. CONCLUSIONS: Ablated tubular cells are exclusively replaced by resident
      tubular cell proliferation in a process dependent on PDGFRbeta-mediated
      communication between the renal interstitium and the tubular system.

PMID- 29444907
TI  - Response to: 'Bisphosphonates reduce the risk of knee replacement: we need more
      analyses!' by Li et al.

PMID- 29444908
TI  - Impaired long-term immune protection following pneumococcal 13-valent/23-valent
      polysaccharide vaccine in systemic lupus erythematosus (SLE).

PMID- 29444909
TI  - Correction to "Mrp3 Transports Clopidogrel Acyl Glucuronide from the Hepatocytes
      into Blood".

PMID- 29444912
TI  - Analysis of airway pathology in COPD using a combination of computed tomography,
      micro-computed tomography and histology.
AB  - The small conducting airways are the major site of obstruction in chronic
      obstructive pulmonary disease (COPD). This study examined small airway pathology
      using a novel combination of multidetector row computed tomography (MDCT), micro
      computed tomography (microCT) and histology.Airway branches visible on specimen
      MDCT were counted and the dimensions of the third- to fifth-generation airways
      were computed, while the terminal bronchioles (designated TB), preterminal
      bronchioles (TB-1) and pre-preterminal bronchioles (TB-2) were examined with
      microCT and histology in eight explanted lungs with end-stage COPD and seven
      unused donor lungs that served as controls.On MDCT, COPD lungs showed a decrease
      in the number of 2-2.5 mm diameter airways and the lumen area of fifth-generation
      airways, while on microCT there was a reduction in the number of terminal
      bronchioles as well as a decrease in the luminal areas, wall volumes and alveolar
      attachments to the walls of TB, TB-1 and TB-2 bronchioles. The combination of
      microCT and histology showed increased B-cell infiltration into the walls of TB-1
      and TB-2 bronchioles, and this change was correlated with a reduced number of
      alveolar attachments in COPD.Small airways disease extends from 2 mm diameter
      airways to the terminal bronchioles in COPD. Destruction of alveolar attachments
      may be driven by a B-cell-mediated immune response in the preterminal
      bronchioles.

PMID- 29444910
TI  - The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of
      GEPNET cell lines.
AB  - Experimental models of neuroendocrine tumour disease are scarce, and no
      comprehensive characterisation of existing gastroenteropancreatic neuroendocrine
      tumour (GEPNET) cell lines has been reported. In this study, we aimed to define
      the molecular characteristics and therapeutic sensitivity of these cell lines. We
      therefore performed immunophenotyping, copy number profiling, whole-exome
      sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four
      cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype
      while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell
      lines were identified as lymphoblastoid. Characterisation of remaining authentic
      GEPNET cell lines by copy number profiling showed that GOT1, among other
      chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4
      gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and
      CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2 Whole-exome
      sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in
      QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P
      STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines
      from pancreatic NETs to a greater extent, when compared to small intestinal NETs,
      were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells
      originating from the small intestine were considerably more sensitive to a group
      of HDAC inhibitors. Taken together, our results provide a comprehensive
      characterisation of GEPNET cell lines, demonstrate their relevance as
      neuroendocrine tumour models and explore their therapeutic sensitivity to a broad
      range of inhibitors.

PMID- 29444913
TI  - Lung transplantation after allogeneic stem cell transplantation: a pan-European
      experience.
AB  - Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of
      allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring
      subsequent 5-year survival of 50%. Lung transplantation is rarely performed in
      this setting due to concomitant extrapulmonary morbidity, excessive
      immunosuppression and concerns about recurring malignancy being considered
      contraindications. This study assesses survival in highly selected patients
      undergoing lung transplantation for LONIPCs after SCT.SCT patients undergoing
      lung transplantation at 20 European centres between 1996 and 2014 were included.
      Clinical data pre- and post-lung transplantation were reviewed. Propensity score
      matched controls were generated from the Eurotransplant and Scandiatransplant
      registries. Kaplan-Meier survival analysis and Cox proportional hazard regression
      models evaluating predictors of graft loss were performed.Graft survival at 1, 3
      and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved
      comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%),
      with prior mechanical ventilation (HR 6.9, 95% CI 1.0-46.7; p<0.001) the leading
      risk factor. No SCT-specific risk factors were identified. Recurring malignancy
      occurred in four patients (4%). Lung transplantation <2 years post-SCT increased
      all-cause 1-year mortality (HR 7.5, 95% CI 2.3-23.8; p=0.001).Lung
      transplantation outcomes following SCT were comparable to other end-stage
      diseases. Lung transplantation should be considered feasible in selected
      candidates. No SCT-specific factors influencing outcome were identified within
      this carefully selected patient cohort.

PMID- 29444915
TI  - Predictors of accelerated decline in lung function in adult-onset asthma.
AB  - Little is known about the prognosis of adults with new-onset asthma. Cross
      sectional studies suggest that these patients may exhibit accelerated decline in
      forced expiratory volume in 1 s (FEV1). However, risk factors for accelerated
      decline in lung function have not yet been identified.We aimed to identify these
      risk factors in a prospective 5-year follow-up study in 200 adults with newly
      diagnosed asthma. In the current study, clinical, functional and inflammatory
      parameters were assessed annually for 5 years. Linear mixed-effects models were
      used to identify predictors.Evaluable lung function sets of 141 patients were
      available. Median (interquartile range) change in post-bronchodilator FEV1 was 
      17.5 (-54.2 to +22.4) mL per year. Accelerated decline in FEV1 was defined by the
      lower quartile of decline (>54.2 mL per year). Nasal polyps, number of blood and
      sputum eosinophils, body mass index, and level of exhaled nitric oxide were
      univariably associated with decline in lung function. Only the latter two were
      independently associated. Using cut-off values to identify patients at highest
      risk showed accelerated decline in FEV1 in all patients with combined exhaled
      nitric oxide fraction (FeNO) >=57 ppb and body mass index (BMI) <=23 kg.m-2We
      conclude that adults with new-onset asthma with both high levels of exhaled
      nitric oxide and low BMI are at risk of accelerated decline in lung function.

PMID- 29444914
TI  - Palatal prolapse as a signature of expiratory flow limitation and inspiratory
      palatal collapse in patients with obstructive sleep apnoea.
AB  - In some individuals with obstructive sleep apnoea (OSA), the palate prolapses
      into the velopharynx during expiration, limiting airflow through the nose or
      shunting it out of the mouth. We hypothesised that this phenomenon causes
      expiratory flow limitation (EFL) and is associated with inspiratory "isolated"
      palatal collapse. We also wanted to provide a robust noninvasive means to
      identify this mechanism of obstruction.Using natural sleep endoscopy, 1211
      breaths from 22 OSA patients were scored as having or not having palatal
      prolapse. The patient-level site of collapse (tongue-related, isolated palate,
      pharyngeal lateral walls and epiglottis) was also characterised. EFL was
      quantified using expiratory resistance at maximal epiglottic pressure. A
      noninvasive EFL index (EFLI) was developed to detect the presence of palatal
      prolapse and EFL using the flow signal alone. In addition, the validity of using
      nasal pressure was assessed.A cut-off value of EFLI >0.8 detected the presence of
      palatal prolapse and EFL with an accuracy of >95% and 82%, respectively. The
      proportion of breaths with palatal prolapse predicted isolated inspiratory
      palatal collapse with 90% accuracy.This study demonstrates that expiratory
      palatal prolapse can be quantified noninvasively, is associated with EFL and
      predicts the presence of inspiratory isolated palatal collapse.

PMID- 29444916
TI  - Low uptake of palliative care for COPD patients within primary care in the UK.
AB  - Mortality and symptom burden from chronic obstructive pulmonary disease (COPD)
      and lung cancer are similar but there is thought to be an inequality in
      palliative care support (PCS) between diseases. This nationally representative
      study assessed PCS for COPD patients within primary care in the UK.This was a
      cohort study using electronic healthcare records (2004-2015). Factors associated
      with receiving PCS were assessed using logistic regression for the whole cohort
      and deceased patients.There were 92 365 eligible COPD patients, of which 26 135
      died. Only 7.8% of the whole cohort and 21.4% of deceased patients received PCS.
      Lung cancer had a strong association with PCS compared with other patient
      characteristics, including Global Initiative for Chronic Obstructive Lung Disease
      stage and Medical Research Council Dyspnoea score (whole cohort, lung cancer: OR
      14.1, 95% CI 13.1-15; deceased patients, lung cancer: OR 6.5, 95% CI 6-7). Only
      16.7% of deceased COPD patients without lung cancer received PCS compared with
      56.5% of deceased patients with lung cancer. In patients that received PCS, lung
      cancer co-diagnosis significantly increased the chances of receiving PCS before
      the last month of life (1-6 versus <=1 month pre-death: risk ratio 1.4, 95% CI
      1.3-1.7).Provision of PCS for COPD patients in the UK is inadequate. Lung cancer,
      not COPD, was the dominant driver for COPD patients to receive PCS.

PMID- 29444918
TI  - Immunotherapy: a new standard of care in thoracic malignancies? A summary of the
      European Respiratory Society research seminar of the Thoracic Oncology Assembly.
AB  - In May 2017, the second European Respiratory Society research seminar of the
      Thoracic Oncology Assembly entitled "Immunotherapy, a new standard of care in
      thoracic malignancies?" was held in Paris, France. This seminar provided an
      opportunity to review the basis of antitumour immunity and to explain how immune
      checkpoint inhibitors (ICIs) work. The main therapeutic trials that have resulted
      in marketing authorisations for use of ICIs in lung cancer were reported. A
      particular focus was on the toxicity of these new molecules in relation to their
      immune-related adverse events. The need for biological selection, currently based
      on immunohistochemistry testing to identify the tumour expression of programmed
      death ligand (PD-L)1, was stressed, as well as the need to harmonise PD-L1
      testing and techniques. Finally, sessions were dedicated to the combination of
      ICIs and radiotherapy and the place of ICIs in nonsmall cell lung cancer with
      oncogenic addictions. Finally, an important presentation was dedicated to the
      future of antitumour vaccination and of all ongoing trials in thoracic oncology.

PMID- 29444917
TI  - Asthma treatment impacts time to pregnancy: evidence from the international SCOPE
      study.

PMID- 29444919
TI  - Tracheal replacement.
AB  - Tracheal reconstruction is one of the greatest challenges in thoracic surgery
      when direct end-to-end anastomosis is impossible or after this procedure has
      failed. The main indications for tracheal reconstruction include malignant
      tumours (squamous cell carcinoma, adenoid cystic carcinoma), tracheoesophageal
      fistula, trauma, unsuccessful surgical results for benign diseases and congenital
      stenosis. Tracheal substitutes can be classified into five types: 1) synthetic
      prosthesis; 2) allografts; 3) tracheal transplantation; 4) tissue engineering;
      and 5) autologous tissue composite. The ideal tracheal substitute is still
      unclear, but some techniques have shown promising clinical results. This article
      reviews the advantages and limitations of each technique used over the past few
      decades in clinical practice. The main limitation seems to be the capacity for
      tracheal tissue regeneration. The physiopathology behind this has yet to be fully
      understood. Research on stem cells sparked much interest and was thought to be a
      revolutionary technique; however, the poor long-term results of this approach
      highlight that there is a long way to go in this research field. Currently, an
      autologous tissue composite, with or without a tracheal allograft, is the only
      long-term working solution for every aetiology, despite its technical complexity
      and setbacks.

PMID- 29444920
TI  - Dyspnoea modifies the recognition of fearful expressions by healthy humans.

PMID- 29444921
TI  - Tuberculosis re-treatment after exclusion of rifampicin resistance.

PMID- 29444922
TI  - Putting the brake on accelerated lung function decline in asthma.

PMID- 29444923
TI  - Palliative care for people with COPD: effective but underused.

PMID- 29444924
TI  - Truth be told: not all nudging is bullshit.

PMID- 29444925
TI  - Increasing Incidence and Prevalence of World Health Organization Groups 1 to 4
      Pulmonary Hypertension: A Population-Based Cohort Study in Ontario, Canada.
AB  - BACKGROUND: The World Health Organization recognizes 5 groups of pulmonary
      hypertension (PH), categorized by pathogenesis or comorbidity: 1-pulmonary
      arterial hypertension 2-left-heart disease, 3-lung disease and hypoxia 4-chronic
      thromboembolic disease, and 5-miscellaneous. The epidemiology of PH, apart from
      group 1, is largely unknown. METHODS AND RESULTS: We describe incidence,
      prevalence, comorbidities, mortality and prescribing patterns for groups 1 to 4
      PH from 1993 to 2012. Case definitions are based on hospitalizations and
      emergency department visits, using the Institute for Clinical Evaluative Sciences
      data, which comprises linked databases of universal coverage health service
      records for Ontario residents. This cohort included 50 529 patients with PH. The
      annual incidence of adult PH increased from 2003 to 2012 from 24.1 to 28.7
      cases/100 000 population and the annual prevalence from 1993 to 2012 from 99.8 to
      127.3 cases/100 000 population, respectively. The most common form of adult PH
      was group 2, alone (34.2%) or combined with group 3 PH (29.3%). A diagnosis of PH
      increased the 1-year standardized mortality ratio 7.2-fold. Mortality in adults
      with PH was 13.0%, 36.4%, and 62.4%, at 30 days, 1 year, and 5 years,
      respectively. Mortality was highest in groups 2 and 3 and lowest in group 1. PH
      was present in only 3.6% of people with left heart disease, 0.7% with lung
      disease, and 1.4% with thromboembolic disease, suggesting that PH is a relatively
      rare complication of these common diseases. Children (age<16 years) accounted for
      3.6% of the cohort. In children group 1 PH was most common (65.2%), and 5-year
      mortality was lower (21.4%) than in adults. Group 1-specific PH therapies were
      increasingly prescribed over time and paradoxically were often used in patients
      who seemed to have group 2, PH based on diagnostic codes indicating left heart
      disease. CONCLUSIONS: The incidence and prevalence of adult PH are increasing.
      Groups 2 and 3 are the most common and lethal forms of PH. This study identifies
      an emerging epidemic of PH that likely has substantial adverse health and
      economic implications.

PMID- 29444927
TI  - High-Sensitivity Troponin Highlights the Need for New Methods to Evaluate
      Diagnostic Tests.

PMID- 29444928
TI  - The Growing Burden of Pulmonary Hypertension in the Modern Era: A Zebra No More?

PMID- 29444926
TI  - High-Sensitivity Cardiac Troponin I and the Diagnosis of Coronary Artery Disease
      in Patients With Suspected Angina Pectoris.
AB  - BACKGROUND: We determined whether high-sensitivity cardiac troponin I can improve
      the estimation of the pretest probability for obstructive coronary artery disease
      (CAD) in patients with suspected stable angina. METHODS AND RESULTS: In a
      prespecified substudy of the SCOT-HEART trial (Scottish Computed Tomography of
      the Heart), plasma cardiac troponin was measured using a high-sensitivity single
      molecule counting assay in 943 adults with suspected stable angina who had
      undergone coronary computed tomographic angiography. Rates of obstructive CAD
      were compared with the pretest probability determined by the CAD Consortium risk
      model with and without cardiac troponin concentrations. External validation was
      undertaken in an independent study population from Denmark comprising 487
      patients with suspected stable angina. Higher cardiac troponin concentrations
      were associated with obstructive CAD with a 5-fold increase across quintiles (9%
      48%; P<0.001) independent of known cardiovascular risk factors (odds ratio, 1.35;
      95% confidence interval, 1.25-1.46 per doubling of troponin). Cardiac troponin
      concentrations improved the discrimination and calibration of the CAD Consortium
      model for identifying obstructive CAD (C statistic, 0.788-0.800; P=0.004;
      chi2=16.8 [P=0.032] to 14.3 [P=0.074]). The updated model also improved
      classification of the American College of Cardiology/American Heart Association
      pretest probability risk categories (net reclassification improvement, 0.062; 95%
      confidence interval, 0.035-0.089). The revised model achieved similar
      improvements in discrimination and calibration when applied in the external
      validation cohort. CONCLUSIONS: High-sensitivity cardiac troponin I concentration
      is an independent predictor of obstructive CAD in patients with suspected stable
      angina. Use of this test may improve the selection of patients for further
      investigation and treatment. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT01149590.

PMID- 29444929
TI  - Development and External Validation of Prediction Models for 10-Year Survival of
      Invasive Breast Cancer. Comparison with PREDICT and CancerMath.
AB  - Purpose: To compare PREDICT and CancerMath, two widely used prognostic models for
      invasive breast cancer, taking into account their clinical utility. Furthermore,
      it is unclear whether these models could be improved.Experimental Design: A
      dataset of 5,729 women was used for model development. A Bayesian variable
      selection algorithm was implemented to stochastically search for important
      interaction terms among the predictors. The derived models were then compared in
      three independent datasets (n = 5,534). We examined calibration, discrimination,
      and performed decision curve analysis.Results: CancerMath demonstrated worse
      calibration performance compared with PREDICT in estrogen receptor (ER)-positive
      and ER-negative tumors. The decline in discrimination performance was -4.27% (
      6.39 to -2.03) and -3.21% (-5.9 to -0.48) for ER-positive and ER-negative tumors,
      respectively. Our new models matched the performance of PREDICT in terms of
      calibration and discrimination, but offered no improvement. Decision curve
      analysis showed predictions for all models were clinically useful for treatment
      decisions made at risk thresholds between 5% and 55% for ER-positive tumors and
      at thresholds of 15% to 60% for ER-negative tumors. Within these threshold
      ranges, CancerMath provided the lowest clinical utility among all the
      models.Conclusions: Survival probabilities from PREDICT offer both improved
      accuracy and discrimination over CancerMath. Using PREDICT to make treatment
      decisions offers greater clinical utility than CancerMath over a range of risk
      thresholds. Our new models performed as well as PREDICT, but no better,
      suggesting that, in this setting, including further interaction terms offers no
      predictive benefit. Clin Cancer Res; 24(9); 2110-5. (c)2018 AACR.

PMID- 29444930
TI  - Immunophenotyping of Newly Diagnosed and Recurrent Glioblastoma Defines Distinct
      Immune Exhaustion Profiles in Peripheral and Tumor-infiltrating Lymphocytes.
AB  - Purpose: Immunotherapeutic treatment strategies for glioblastoma (GBM) are under
      investigation in clinical trials. However, our understanding of the immune
      phenotype of GBM-infiltrating T cells (tumor-infiltrating lymphocytes; TILs) and
      changes during disease progression is limited. Deeper insight is urgently needed
      to therapeutically overcome tumor-induced immune exhaustion.Experimental Design:
      We used flow cytometry and cytokine assays to profile TILs and peripheral blood
      lymphocytes (PBLs) from patients with GBM, comparing newly diagnosed or recurrent
      GBM to long-term survivors (LTS) and healthy donors. TCR sequencing was performed
      on paired samples of newly diagnosed and recurrent GBM.Results: We identified a
      clear immune signature of exhaustion and clonal restriction in the TILs of
      patients with GBM. Exhaustion of CD8+ TILs was defined by an increased prevalence
      of PD-1+, CD39+, Tim-3+, CD45RO+, HLA-DR+ marker expression, and exhibition of an
      effector-/transitional memory differentiation phenotype, whereas KLRG1 and CD57
      were underrepresented. Immune signatures were similar in primary and recurrent
      tumors; however, restricted TCR repertoire clonality and a more activated memory
      phenotype were observed in TILs from recurrent tumors. Moreover, a reduced
      cytokine response to PHA stimulation in the blood compartment indicates a
      dysfunctional peripheral T-cell response in patients with GBM. LTS displayed a
      distinct profile, with abundant naive and less exhausted CD8+ T
      cells.Conclusions: TILs and PBLs exhibit contrasting immune profiles, with a
      distinct exhaustion signature present in TILs. While the exhaustion profiles of
      primary and recurrent GBM are comparable, TCR sequencing demonstrated a
      contracted repertoire in recurrent GBM, concomitant with an increased frequency
      of activated memory T cells in recurrent tumors. Clin Cancer Res; 24(17); 4187
      200. (c)2018 AACRSee related commentary by Jackson and Lim, p. 4059.

PMID- 29444931
TI  - Complete Remission with Reduction of High-Risk Clones following Haploidentical NK
      Cell Therapy against MDS and AML.
AB  - Purpose: To evaluate the safety, efficacy, and immunobiological correlates of
      allogeneic NK-cell-based therapy in primary chemotherapy-refractory or relapsed
      high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo
      AML patients.Experimental Design: Sixteen patients received
      fludarabine/cyclophosphamide conditioning combined with total lymphoid
      irradiation followed by adoptive immunotherapy with IL2-activated haploidentical
      NK cells.Results: NK-cell infusions were well-tolerated, with only transient
      adverse events observed in the 16 patients. Six patients achieved objective
      responses with complete remission (CR), marrow CR, or partial remission (PR).
      Five patients proceeded to allogeneic hematopoietic stem cell transplantation
      (HSCT). Three patients are still free from disease >3 years after treatment. All
      evaluable patients with objective responses (5/5 evaluable) had detectable donor
      NK cells at days 7/14 following infusion and displayed reduction of tumor cell
      clones, some of which carried poor prognosis mutations. Residual lin
      CD34+CD123+CD45RA+ blast cells in responders had increased total HLA class I and
      HLA-E expression. Responding patients displayed less pronounced activation of
      CD8+ T cells and lower levels of inflammatory cytokines following NK-cell
      infusion. Intriguingly, despite omission of systemic IL2, all patients displayed
      increased frequencies of activated Ki-67+CD127-FoxP3+CD25hiCD4+ Treg cells of
      recipient origin following NK-cell therapy.Conclusions: Overall, this study
      suggests that high-risk MDS is responsive to NK-cell therapy and supports the use
      of haploidentical NK-cell infusions as a bridge to HSCT in refractory patients.
      Objective clinical responses and reduction of high-risk clones were associated
      with detectable donor-derived NK cells, immunoediting of residual blast cells,
      and less pronounced host immune activation. Clin Cancer Res; 24(8); 1834-44.
      (c)2018 AACR.

PMID- 29444932
TI  - Artificial stone-associated silicosis in the UK.

PMID- 29444933
TI  - PNLDC1, mouse pre-piRNA Trimmer, is required for meiotic and post-meiotic male
      germ cell development.
AB  - PIWI-interacting RNAs (piRNAs) are germ cell-specific small RNAs essential for
      retrotransposon gene silencing and male germ cell development. In piRNA
      biogenesis, the endonuclease MitoPLD/Zucchini cleaves long, single-stranded RNAs
      to generate 5' termini of precursor piRNAs (pre-piRNAs) that are consecutively
      loaded into PIWI-family proteins. Subsequently, these pre-piRNAs are trimmed at
      their 3'-end by an exonuclease called Trimmer. Recently, poly(A)-specific
      ribonuclease-like domain-containing 1 (PNLDC1) was identified as the pre-piRNA
      Trimmer in silkworms. However, the function of PNLDC1 in other species remains
      unknown. Here, we generate Pnldc1 mutant mice and analyze small RNAs in their
      testes. Our results demonstrate that mouse PNLDC1 functions in the trimming of
      both embryonic and post-natal pre-piRNAs. In addition, piRNA trimming defects in
      embryonic and post-natal testes cause impaired DNA methylation and reduced MIWI
      expression, respectively. Phenotypically, both meiotic and post-meiotic arrests
      are evident in the same individual Pnldc1 mutant mouse. The former and latter
      phenotypes are similar to those of MILI and MIWI mutant mice, respectively. Thus,
      PNLDC1-mediated piRNA trimming is indispensable for the function of piRNAs
      throughout mouse spermatogenesis.

PMID- 29444934
TI  - Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and
      eosinophil peroxidase modify GSH and protein.
AB  - alpha-Chlorofatty aldehydes (alpha-ClFALDs) and alpha-bromofatty aldehydes (alpha
      BrFALDs) are produced in activated neutrophils and eosinophils. This study
      investigated the ability of alpha-BrFALD and alpha-ClFALD to react with the
      thiols of GSH and protein cysteinyl residues. Initial studies showed that 2
      bromohexadecanal (2-BrHDA) and 2-chlorohexadecanal (2-ClHDA) react with GSH
      producing the same fatty aldehyde-GSH adduct (FALD-GSH). In both synthetic and
      cellular reactions, FALD-GSH production was more robust with 2-BrHDA compared
      with 2-ClHDA as precursor. NaBr-supplemented phorbol myristate acetate (PMA)
      activated neutrophils formed more alpha-BrFALD and FALD-GSH compared with non
      NaBr-supplemented neutrophils. Primary human eosinophils, which preferentially
      produce hypobromous acid and alpha-BrFALD, accumulated FALD-GSH following PMA
      stimulation. Mice exposed to Br2 gas had increased levels of both alpha-BrFALD
      and FALD-GSH in the lungs, as well as elevated systemic plasma levels of FALD-GSH
      in comparison to mice exposed to air. Similar relative reactivity of alpha-ClFALD
      and alpha-BrFALD with protein thiols was shown using click analogs of these
      aldehydes. Collectively, these data demonstrate that GSH and protein adduct
      formation are much greater as a result of nucleophilic attack of cysteinyl
      residues on alpha-BrFALD compared with alpha-ClFALD, which was observed in both
      primary leukocytes and in mice exposed to bromine gas.

PMID- 29444935
TI  - Adenylyl cyclase 1 as a major isoform to generate cAMP signaling for apoA-1
      mediated cholesterol efflux pathway.
AB  - HDL apoA-1-mediated cholesterol efflux pathway requires multiple cellular
      proteins and signal transduction processes, including adenylyl cyclase (AC)/cAMP
      signaling. Due to the existence of multiple transmembrane AC isoforms, it was not
      known how many AC isoforms are expressed and which ones are essential for
      cholesterol efflux in macrophage foam cells. These questions were investigated in
      THP-1 macrophages in this study. Quantitative RT-PCR detected mRNAs for all nine
      transmembrane AC isoforms, but only the mRNA and protein of the AC1 isoform were
      consistently upregulated by cholesterol loading and apoA-1. AC1 shRNA
      interference decreased AC1 mRNA and protein levels, resulting in reduction of
      apoA-1-mediated cAMP production and cholesterol efflux, while the intracellular
      cholesterol levels remained high. Confocal microscopy showed that apoA-1 promoted
      translocation of cholesterol and formation of cholesterol-apoA-1 complexes
      (protrusions) on the cholesterol-loaded macrophage surface. AC1 shRNA-interfered
      macrophages showed no translocation of cholesterol to the cell surface. AC1 shRNA
      interference also disrupted cellular localization of the intracellular
      cholesterol indicator protein adipophillin, and the expression as well as surface
      translocation of ABCA1. Together, our results show that AC1 is a major isoform
      for apoA-1-activated cAMP signaling to promote cholesterol transport and
      exocytosis to the surface of THP-1 macrophage foam cells.

PMID- 29444936
TI  - Aspirin alone and combined with a statin suppresses eicosanoid formation in human
      colon tissue.
AB  - Eicosanoids, including prostaglandins (PGs) and thromboxanes, are broadly
      bioactive lipid mediators and increase colon tumorigenesis possibly through
      chronic inflammatory mechanisms. Epidemiological and experimental data suggest
      that acetylsalicylic acid (ASA) helps prevent colorectal cancer (CRC), possibly
      through cyclooxygenase (COX)-mediated suppression of eicosanoid, particularly
      PGE2, formation. Recent studies suggest that statins prevent CRC and improve
      survival after diagnosis. We identified patients on ASA and/or statin treatment
      undergoing routine colonoscopy and measured eicosanoid levels in colonic mucosa
      with targeted metabolomics technology (LC-MS/MS). ASA-treated individuals (n =
      27) had significantly lower tissue eicosanoid levels of most COX-derived
      metabolites than untreated individuals (n = 31). In contrast, COX-derived lipid
      metabolites tended to be higher in patients with statin treatment (n = 7) as
      compared with those not receiving statins (n = 24). This effect was not
      discernible in subjects treated with ASA and statins (n = 11): Individuals
      treated with both drugs showed a pronounced suppression of COX-derived
      eicosanoids in colon tissue, even compared with subjects treated with ASA alone.
      Our data from a routine clinical setting support the hypothesis that ASA and
      statins could inhibit CRC development via lipid mediator modification. Further
      studies should directly investigate the effect of dual ASA and statin treatment
      on colon tumorigenesis in humans.

PMID- 29444937
TI  - Maraviroc is associated with latent HIV-1 reactivation through NF-kappaB
      activation in resting CD4+ T cells from HIV-Infected Individuals on Suppressive
      Antiretroviral Therapy.
AB  - Maraviroc is a CCR5 antagonist used in the treatment of HIV-1 infection. We and
      others have suggested that maraviroc could reactivate latent HIV-1. To test the
      latency reversing potential of maraviroc and the mechanisms involved, we
      performed a phase-II, single-center, open-label study in which maraviroc was
      administered for 10 days to 20 HIV-1-infected individuals on suppressive
      antiretroviral therapy (Eudra CT: 2012-003215-66). All patients completed full
      maraviroc dosing and follow up. The primary endpoint was to study whether
      maraviroc may reactivate HIV-1 latency, eliciting signalling pathways involved in
      the viral reactivation. An increase in HIV-1 transcription in resting CD4+ T
      cells, estimated by HIV-1 unspliced RNA, was observed. Moreover, activation of
      the NF-kappaB transcription factor was observed in these cells. In contrast, AP-1
      and NFAT activity was not detected. To elucidate the mechanism of NF-kappaB
      activation by maraviroc, we have evaluated in HeLa P4 C5 cells, which stably
      express CCR5, if maraviroc could be acting as a partial CCR5-agonist, with no
      other mechanisms or pathways involved. Our results show that maraviroc can induce
      NF-kappaB activity and NF-kappaB target genes expression by CCR5 binding, since
      the use of TAK779, a CCR5 inhibitor, blocked NF-kappaB activation and
      functionality. Taken together, we show that maraviroc may have a role in the
      activation of latent virus transcription through the activation of NF-kappaB as a
      result of binding CCR5. Our results strongly support a novel use of maraviroc as
      a potential latency reversal agent in HIV-1-infected patients.IMPORTANCE HIV-1
      persistence in a small pool of long-lived latently infected resting CD4+ T-cells
      is a major barrier to viral eradication in HIV-1-infected patients on
      antiretroviral therapy. A potential strategy to cure HIV-1-infection is the use
      of latency reversing agents to eliminate the reservoirs established in resting
      CD4+ T-cells. As no drug has been shown to be completely effective so far, the
      search for new drugs and combinations remains a priority in the HIV cure. We
      examined the ability of maraviroc, a CCR5-antagonist used as an antiretroviral
      drug, to activate latent HIV-1 in infected-individuals on antiretroviral therapy.
      The study showed that maraviroc can activate NF-kappaB and, subsequently, induce
      latent HIV-1-transcription in resting CD4+ T-cells from HIV-1-infected
      individuals on suppressive antiretroviral therapy. Additional interventions will
      be needed to eliminate latent HIV-1 infection. Our results suggest that maraviroc
      may be a new latency reversing agent to interfere with HIV-1 persistence during
      antiretroviral therapy.

PMID- 29444938
TI  - Intranasal Live Influenza Vaccine Priming Elicits Localized B Cell Responses in
      Mediastinal Lymph Nodes.
AB  - Pandemic live attenuated influenza vaccines (pLAIV) prime subjects for a robust
      neutralizing antibody response upon subsequent administration of a pandemic
      inactivated subunit vaccine (pISV). However, a difference was not detected in H5
      specific memory B cells in the peripheral blood between pLAIV-primed and unprimed
      subjects prior to pISV boost. To investigate the mechanism underlying pLAIV
      priming, we vaccinated groups of 12 African green monkeys (AGMs) with H5N1 pISV
      or pLAIV alone or H5N1 pLAIV followed by pISV and examined immunity systemically
      and in local draining lymph nodes (LN). The AGM model recapitulated the serologic
      observations from clinical studies. Interestingly, H5N1 pLAIV induced robust
      germinal center B cell responses in the mediastinal LN (MLN). Subsequent boosting
      with H5N1 pISV drove increases in H5-specific B cells in the axillary LN, spleen,
      and circulation in H5N1 pLAIV-primed animals. Thus, H5N1 pLAIV primes localized B
      cell responses in the MLN that are recalled systemically following pISV boost.
      These data provide mechanistic insights for the generation of robust humoral
      responses via prime-boost vaccination.IMPORTANCE We have previously shown that
      pandemic live attenuated influenza vaccines (pLAIV) prime for a rapid and robust
      antibody response on subsequent administration of inactivated subunit vaccine
      (pISV). This is observed even in individuals who had undetectable antibody (Ab)
      responses following the initial vaccination. To define the mechanistic basis of
      pLAIV priming, we turned to a nonhuman primate model and performed a detailed
      analysis of B cell responses in systemic and local lymphoid tissues following
      prime-boost vaccination with pLAIV and pISV. We show that the nonhuman primate
      model recapitulates the serologic observations from clinical studies. Further, we
      found that pLAIVs induced robust germinal center B cell responses in the
      mediastinal lymph node. Subsequent boosting with pISV in pLAIV-primed animals
      resulted in detection of B cells in the axillary lymph nodes, spleen, and
      peripheral blood. We demonstrate that intranasally administered pLAIV elicits a
      highly localized germinal center B cell response in the mediastinal lymph node
      that is rapidly recalled following pISV boost into germinal center reactions at
      numerous distant immune sites.

PMID- 29444939
TI  - Single-Cell Analysis of the Impact of Host Cell Heterogeneity on Infection with
      Foot-and-Mouth Disease Virus.
AB  - Viral infection and replication are affected by host cell heterogeneity, but the
      mechanisms underlying the effects remain unclear. Using single-cell analysis, we
      investigated the effects of host cell heterogeneity, including cell size,
      inclusion, and cell cycle, on foot-and-mouth disease virus (FMDV) infection
      (acute and persistent infections) and replication. We detected various viral
      genome replication levels in FMDV-infected cells. Large cells and cells with a
      high number of inclusions generated more viral RNA copies and viral protein and a
      higher proportion of infectious cells than other cells. Additionally, we found
      that the viral titer was 10- to 100-fold higher in cells in G2/M than those in
      other cell cycle phases and identified a strong correlation between cell size,
      inclusion, and cell cycle heterogeneity, which all affected the infection and
      replication of FMDV. Furthermore, we demonstrated that host cell heterogeneity
      influenced the adsorption of FMDV due to differences in the levels of FMDV
      integrin receptors expression. Collectively, these results further our
      understanding of the evolution of a virus in a single host cell.IMPORTANCE It is
      important to understand how host cell heterogeneity affects viral infection and
      replication. Using single-cell analysis, we found that viral genome replication
      levels exhibited dramatic variability in foot-and-mouth disease virus (FMDV)
      infected cells. We also found a strong correlation between heterogeneity in cell
      size, inclusion number, and cell cycle status and that all of these
      characteristics affect the infection and replication of FMDV. Moreover, we found
      that host cell heterogeneity influenced the viral adsorption as differences in
      the levels of FMDV integrin receptors' expression. This study provided new ideas
      for the studies of correlation between FMDV infection mechanisms and host cells.

PMID- 29444940
TI  - Dynamics of Evolution of Poliovirus Neutralizing Antigenic Sites and Other Capsid
      Functional Domains during a Large and Prolonged Outbreak.
AB  - We followed the dynamics of capsid amino acid replacement among 403 Nigerian
      outbreak isolates of type 2 circulating vaccine-derived poliovirus (cVDPV2) from
      2005 through 2011. Four different functional domains were analyzed: 1)
      neutralizing antigenic (NAg) sites, 2) residues binding the poliovirus receptor
      (PVR), 3) VP1 residues 1-32, and 4) the capsid structural core. Amino acid
      replacements mapped to 37 of 43 positions across all 4 NAg sites; the most
      variable and polymorphic residues were in NAg sites 2 and 3b. The most divergent
      of the 120 NAg variants had no more than 5 replacements in all NAg sites, and
      were still neutralized at titers similar to those of Sabin 2. PVR-binding
      residues were less variable (25 different variants; 0-2 replacements/isolate;
      30/44 invariant positions), with the most variable residues also forming parts of
      NAg sites 2 and 3a. Residues 1-32 of VP1 were highly variable (133 different
      variants; 0-6 replacements/isolate; 5/32 invariant positions), with residues 1-18
      predicted to form a well-conserved amphipathic helix. Replacement events were
      dated by mapping them onto the branches of time-scaled phylogenies. Rates of
      amino acid replacement varied widely across positions and followed no simple
      substitution model. Replacements into the structural core were the most
      conservative and were fixed at an overall rate ~20-fold lower than rates for the
      NAg sites and VP1 1-32, and ~5-fold lower than the rate for the PVR-binding
      sites. Only VP1-143-Ile, a non-NAg site surface residue and known attenuation
      site, appeared to be under strong negative selection.IMPORTANCE The high rate of
      poliovirus evolution is offset by strong selection against amino acid replacement
      at most positions of the capsid. Consequently, poliovirus vaccines developed from
      strains isolated decades ago have been used worldwide to bring wild polioviruses
      almost to extinction. The apparent antigenic stability of poliovirus obscures a
      dynamic of continuous change within the neutralizing antigenic (NAg) sites.
      During seven years of a large outbreak in Nigeria, the circulating type 2 vaccine
      derived polioviruses generated 120 different NAg site variants via multiple
      independent pathways. Nonetheless, overall antigenic evolution was constrained,
      as no isolate had fixed more than 5 amino acid differences from the Sabin 2 NAg
      sites, and the most divergent isolates were efficiently neutralized by human
      immune sera. Evolution elsewhere in the capsid was also constrained. Amino acids
      binding the poliovirus receptor were strongly conserved, and extensive variation
      in the VP1 amino terminus still conserved a predicted amphipathic helix.

PMID- 29444941
TI  - Lactic Acid Downregulates Viral MicroRNA To Promote Epstein-Barr Virus
      Immortalized B Lymphoblastic Cell Adhesion and Growth.
AB  - High plasma lactate is associated with poor prognosis of many malignancies, but
      its role in virally mediated cancer progression and underlying molecular
      mechanisms are unclear. Epstein-Barr virus (EBV), the first human oncogenic
      virus, causes several cancers, including B-cell lymphoma. Here, we report that
      lactate dehydrogenase A (LDH-A) expression and lactate production are elevated in
      EBV-immortalized B lymphoblastic cells, and lactic acid (LA; acidic lactate) at
      low concentration triggers EBV-infected B-cell adhesion, morphological changes,
      and proliferation in vitro and in vivo Moreover, LA-induced responses of EBV
      infected B cells uniquely occurs in viral latency type III, and it is
      dramatically associated with the inhibition of global viral microRNAs,
      particularly the miR-BHRF1 cluster, and the high expression of SMAD3, JUN, and
      COL1A genes. The introduction of miR-BHRF1-1 blocks the LA-induced effects of EBV
      infected B cells. Thus, this may be a novel mechanism to explain EBV-immortalized
      B lymphoblastic cell malignancy in an LA microenvironment.IMPORTANCE The tumor
      microenvironment is complicated, and lactate, which is created by cell
      metabolism, contributes to an acidic microenvironment that facilitates cancer
      progression. However, how LA operates in virus-associated cancers is unclear.
      Thus, we studied how EBV (the first tumor virus identified in humans; it is
      associated with many cancers) upregulates the expression of LDH-A and lactate
      production in B lymphoma cells. Elevated LA induces adhesion and the growth of
      EBV-infected B cells by inhibiting viral microRNA transcription. Thus, we offer a
      novel understanding of how EBV utilizes an acidic microenvironment to promote
      cancer development.

PMID- 29444942
TI  - A Functional Link between RNA Replication and Virion Assembly in the Potyvirus
      Plum Pox Virus.
AB  - Accurate assembly of viral particles in the potyvirus Plum pox virus (PPV) has
      been shown to depend on the contribution of the multifunctional viral protein
      HCPro. In this study, we show that other viral factors, in addition to the capsid
      protein (CP) and HCPro, are necessary for the formation of stable PPV virions.
      The CP produced in Nicotiana benthamiana leaves from a subviral RNA termed LONG,
      which expresses a truncated polyprotein that lacks P1 and HCPro, together with
      HCPro supplied in trans, was assembled into virus-like particles and remained
      stable after in vitro incubation. In contrast, deletions in multiple regions of
      the LONG coding sequence prevented the CP stabilization mediated by HCPro. In
      particular, we demonstrated that the first 178 amino acids of P3, but not a
      specific nucleotide sequence coding for them, are required for CP stability and
      proper assembly of PPV particles. Using a sequential coagroinfiltration assay, we
      observed that the subviral LONG RNA replicates and locally spreads in N.
      benthamiana leaves expressing an RNA silencing suppressor. The analysis of the
      effect of both point and deletion mutations affecting RNA replication in LONG and
      full-length PPV demonstrated that this process is essential for the assembly of
      stable viral particles. Interestingly, in spite of this requirement, the CP
      produced by a nonreplicating viral RNA can be stably assembled into virions as
      long as it is coexpressed with a replication-proficient RNA. Altogether, these
      results highlight the importance of coupling encapsidation to other viral
      processes to secure a successful infection.IMPORTANCE Viruses of the family
      Potyviridae are among the most dangerous threats for basically every important
      crop, and such socioeconomical relevance has made them a subject of many research
      studies. In spite of this, very little is currently known about proteins and
      processes controlling viral genome encapsidation by the coat protein. In the case
      of Plum pox virus (genus Potyvirus), for instance, we have previously shown that
      the multitasking viral factor HCPro plays a role in the production of stable
      virions. Here, by using this potyvirus as a model, we move further to show that
      additional factors are also necessary for the efficient production of potyviral
      particles. More importantly, a comprehensive screening for such factors led us to
      the identification of a functional link between virus replication and packaging,
      unraveling a previously unknown connection of these two key events of the
      potyviral infection cycle.

PMID- 29444943
TI  - Vaccinia Virus C9 Ankyrin Repeat/F-Box Protein Is a Newly Identified Antagonist
      of the Type I Interferon-Induced Antiviral State.
AB  - Type I interferons (IFNs) induce expression of more than 300 cellular genes that
      provide protection against viruses and other pathogens. For survival, viruses
      evolved defenses to prevent the IFN response or counteract the IFN-induced
      antiviral state. However, because viruses and cells coevolved, the dynamic
      relationship between virus and host is difficult to discern. In the present
      study, we demonstrated that vaccinia virus with a large deletion near the left
      end of the genome had a diminished ability to replicate in cells that had been
      pretreated with beta interferon (IFN-beta), suggesting that one or more of the
      missing 17 open reading frames (ORFs) encode an antagonist of the IFN-induced
      antiviral state. By systematically deleting groups of ORFs and then individual
      ORFs, the C9L gene was shown to be required for IFN resistance. Replication of
      the C9L deletion mutant (vDeltaC9) was impaired in human cells that had been
      pretreated with IFN-beta. Expression of viral early genes occurred, but
      subsequent events, including genome uncoating, genome replication, and
      postreplicative gene expression, were inhibited. Expression of the C9 protein
      occurred prior to genome replication, consistent with an early role in
      counteracting the IFN-induced antiviral state. C9 contains six ankyrin repeat
      motifs and a near C-terminal F-box. Mass spectrometry and immunoblotting
      identified host proteins that copurified with a functional epitope-tagged C9. The
      most abundant proteins were components of the SCF (CUL1, SKP1, F-box) and
      signalosome/deneddylation complexes, which interact with each other, suggesting a
      possible role in proteolysis of one or more interferon-induced
      proteins.IMPORTANCE Poxviruses comprise a family of large DNA viruses that
      replicate in the cytoplasm of vertebrate and insect hosts and cause human and
      zoonotic diseases. In most cases the primary infection is moderated by innate
      immune defenses. Vertebrates, including fish, amphibians, reptiles, birds, and
      mammals, all produce type I interferon homologs. In humans, interferon stimulates
      the synthesis of more than 300 proteins thought to have roles in host defense.
      Conversely, viruses have evolved means to thwart the host defenses. We are
      attempting to deconstruct the established virus-host relationship in order to
      better understand the molecular mechanisms involved. In the present study, we
      identified a vaccinia virus gene that prevents interferon-mediated inhibition of
      very early stages of viral replication and is conserved in orthopoxviruses. The
      viral protein was shown to interact with host proteins involved in proteolysis,
      suggesting that vaccinia virus may subvert the cellular apparatus for its own
      defense.

PMID- 29444944
TI  - The 38K-Mediated Specific Dephosphorylation of the Viral Core Protein P6.9 Plays
      an Important Role in the Nucleocapsid Assembly of Autographa californica Multiple
      Nucleopolyhedrovirus.
AB  - Encapsidation of the viral genomes, leading to the assembly of the nucleocapsids
      to form infectious progeny virions, is a key step in many virus life cycles.
      Baculovirus nucleocapsid assembly is a complex process that involves many
      proteins. Our previous studies showed that the deletion of the core gene 38K
      (ac98) interrupted the nucleocapsid assembly by producing capsid sheaths devoid
      of viral genomes by an unknown mechanism. All homologs of 38K contain conserved
      motifs of the haloacid dehalogenase superfamily, which are involved in phosphoryl
      transfer. The requirements of these motifs for nucleocapsid assembly, confirmed
      in the present study, suggest that 38K may be a functioning haloacid
      dehalogenase. P6.9 is also encoded by a core gene (ac100) and is required for
      viral genome encapsidation. It has been reported that multiple phosphorylated
      species of P6.9 are present in virus-infected cells, while only an
      unphosphorylated species is detected in the budded virus. Therefore, whether 38K
      mediates the dephosphorylation of P6.9 was investigated. An additional
      phosphorylated species of P6.9 in 38K-deleted or -mutated virus-transfected cells
      was detected, and the dephosphorylated sites mediated by 38K were determined by
      mass spectrometry. To assess the effects of dephosphorylation of P6.9 mediated by
      38K on virus replication, these sites were mutated to glutamic acids
      (phosphorylation-mimic mutant) or to alanines (phosphorylation-deficient mutant).
      Studies showed that the nucleocapsid assembly was interrupted in phosphorylation
      mimic mutant virus-transfected cells. Taken together, our findings demonstrate
      that 38K mediates the dephosphorylation of specific sites at the C terminus of
      P6.9, which is essential for viral genome encapsidation.IMPORTANCE Genome
      packaging is a fundamental process in the virus life cycle, and viruses have
      different strategies to perform this step. For several double-stranded DNA
      (dsDNA) viruses, the procapsid is formed before genome encapsidation, which may
      require basic proteins that help to neutralize the nucleic acid charge repulsion
      to facilitate the compaction of the genome within the confined capsid space.
      Baculovirus encodes a small basic protein, P6.9, which is required for a variety
      of processes in the virus infection cycle. The phosphorylation of P6.9 is thought
      to result in nucleocapsid uncoating, while the dephosphorylation of P6.9 is
      involved in viral DNA encapsidation during nucleocapsid assembly. Here, we
      demonstrate that a haloacid dehalogenase homolog encoded by baculovirus core gene
      38K is involved in nucleocapsid assembly by mediating the dephosphorylation of 5
      specific sites at the C terminus of P6.9. This finding contributes to the
      understanding of the mechanisms of virus nucleocapsid assembly.

PMID- 29444945
TI  - Interaction of Human Cytomegalovirus Tegument Proteins ppUL35 and ppUL35A with
      Sorting Nexin 5 Regulates Glycoprotein B (gpUL55) Localization.
AB  - Human cytomegalovirus (HCMV) is a widespread human pathogen that causes
      asymptomatic infection in healthy individuals but poses a serious threat to
      immunocompromised patients. During the late phase of HCMV infection, the viral
      capsid is transported to the cytoplasmic viral assembly center (cVAC), where it
      is enclosed by the tegument protein layer and the viral envelope. The cVAC
      consists of circularly arranged vesicles from the trans-Golgi and endosomal
      networks. The HCMV gene UL35 encodes ppUL35 and its shorter form, ppUL35A. We
      have previously shown that the UL35 gene is involved in HCMV assembly, but it is
      unknown how UL35 proteins regulate viral assembly. Here we show that sorting
      nexin 5 (SNX5), a component of the retromer and part of the retrograde transport
      pathway, interacts with UL35 proteins. Expression of wild-type proteins but not
      mutants defective in SNX5 binding resulted in the cellular redistribution of the
      cation-independent mannose-6-phosphate receptor (CI-M6PR), indicating that UL35
      proteins bind and negatively regulate SNX5 to modulate cellular transport
      pathways. Furthermore, binding of UL35 proteins to SNX5 was required for
      efficient viral replication and for transport of the most abundant HCMV
      glycoprotein B (gB; gpUL55) to the cVAC. These results indicate that ppUL35 and
      ppUL35A control the localization of the essential gB through the regulation of a
      retrograde transport pathway. Thus, this work is the first to define a molecular
      interaction between a tegument protein and a vesicular transport factor to
      regulate glycoprotein localization.IMPORTANCE Human cytomegalovirus is
      ubiquitously present in the healthy population, but reactivation or reinfection
      can cause serious, life-threatening infections in immunocompromised patients. For
      completion of its lytic cycle, human cytomegalovirus induces formation of an
      assembly center where mature virus particles are formed from multiple viral
      proteins. Viral glycoproteins use separate vesicular pathways for transport to
      the assembly center, which are incompletely understood. Our research identified a
      viral structural protein which affects the localization of one of the major
      glycoproteins. We could link this change in glycoprotein localization to an
      interaction of the structural protein with a cellular protein involved in
      regulation of vesicle transport. This increases our understanding of how the
      virus intersects into cellular regulatory pathways to enhance its own
      replication.

PMID- 29444946
TI  - Karyopherin Alpha 6 Is Required for Replication of Porcine Reproductive and
      Respiratory Syndrome Virus and Zika Virus.
AB  - Movement of macromolecules between the cytoplasm and the nucleus occurs through
      the nuclear pore complex (NPC). Karyopherins comprise a family of soluble
      transport factors facilitating the nucleocytoplasmic translocation of proteins
      through the NPC. In this study, we found that karyopherin alpha6 (KPNA6; also
      known as importin alpha7) was required for the optimal replication of porcine
      reproductive and respiratory syndrome virus (PRRSV) and Zika virus (ZIKV), which
      are positive-sense, single-stranded RNA viruses replicating in the cytoplasm. The
      KPNA6 protein level in virus-infected cells was much higher than that in mock
      infected controls, whereas the KPNA6 transcript remains stable. Viral infection
      blocked the ubiquitin-proteasomal degradation of KPNA6, which led to an extension
      of the KPNA6 half-life and the elevation of the KPNA6 level in comparison to mock
      infected cells. PRRSV nsp12 protein induced KPNA6 stabilization. KPNA6 silencing
      was detrimental to the replication of PRRSV, and KPNA6 knockout impaired ZIKV
      replication. Moreover, KPNA6 knockout blocked the nuclear translocation of PRRSV
      nsp1beta but had a minimal effect on two other PRRSV proteins with nuclear
      localization. Exogenous restitution of KPNA6 expression in the KPNA6-knockout
      cells results in restoration of the nuclear translocation of PRRSV nsp1beta and
      the replication of ZIKV. These results indicate that KPNA6 is an important
      cellular factor for the replication of PRRSV and ZIKV.IMPORTANCE Positive-sense,
      single-stranded RNA (+ssRNA) viruses replicate in the cytoplasm of infected
      cells. The roles of transport factors in the nucleocytoplasmic trafficking system
      for the replication of +ssRNA viruses are not known. In this study, we discovered
      that PRRSV and ZIKV viruses needed karyopherin alpha6 (KPNA6), one of the
      transport factors, to enhance the virus replication. Our data showed that viral
      infection induced an elevation of the KPNA6 protein level due to an extension of
      the KPNA6 half-life via viral interference of the ubiquitin-proteasomal
      degradation of KPNA6. Notably, KPNA6 silencing or knockout dramatically reduced
      the replication of PRRSV and ZIKV. PRRSV nsp1beta depended on KPNA6 to
      translocate into the nucleus. In addition, exogenous restitution of KPNA6
      expression in KPNA6-knockout cells led to the restoration of nsp1beta nuclear
      translocation and ZIKV replication. These results reveal a new aspect in the
      virus-cell interaction and may facilitate the development of novel antiviral
      therapeutics.

PMID- 29444947
TI  - Hepatitis C Virus core+1/ARF Protein Modulates the Cyclin D1/pRb Pathway and
      Promotes Carcinogenesis.
AB  - Viruses often encompass overlapping reading frames and unconventional translation
      mechanisms in order to maximize the output from a minimum genome and to
      orchestrate their timely gene expression. Hepatitis C virus (HCV) possesses such
      an unconventional open reading frame (ORF) within the core-coding region,
      encoding an additional protein, initially designated ARFP, F, or core+1. Two
      predominant isoforms of core+1/ARFP have been reported, core+1/L, initiating from
      codon 26, and core+1/S, initiating from codons 85/87 of the polyprotein coding
      region. The biological significance of core+1/ARFP expression remains elusive.
      The aim of the present study was to gain insight into the functional and
      pathological properties of core+1/ARFP through its interaction with the host
      cell, combining in vitro and in vivo approaches. Our data provide strong evidence
      that the core+1/ARFP of HCV-1a stimulates cell proliferation in Huh7-based cell
      lines expressing either core+1/S or core+1/L isoforms and in transgenic liver
      disease mouse models expressing core+1/S protein in a liver-specific manner. Both
      isoforms of core+1/ARFP increase the levels of cyclin D1 and phosphorylated Rb,
      thus promoting the cell cycle. In addition, core+1/S was found to enhance liver
      regeneration and oncogenesis in transgenic mice. The induction of the cell cycle
      together with increased mRNA levels of cell proliferation-related oncogenes in
      cells expressing the core+1/ARFP proteins argue for an oncogenic potential of
      these proteins and an important role in HCV-associated pathogenesis.IMPORTANCE
      This study sheds light on the biological importance of a unique HCV protein. We
      show here that core+1/ARFP of HCV-1a interacts with the host machinery, leading
      to acceleration of the cell cycle and enhancement of liver carcinogenesis. This
      pathological mechanism(s) may complement the action of other viral proteins with
      oncogenic properties, leading to the development of hepatocellular carcinoma. In
      addition, given that immunological responses to core+1/ARFP have been correlated
      with liver disease severity in chronic HCV patients, we expect that the present
      work will assist in clarifying the pathophysiological relevance of this protein
      as a biomarker of disease progression.

PMID- 29444948
TI  - The Superimposed Deubiquitination Effect of OTULIN and Porcine Reproductive and
      Respiratory Syndrome Virus (PRRSV) Nsp11 Promotes Multiplication of PRRSV.
AB  - Linear ubiquitination plays an important role in the regulation of the immune
      response by regulating nuclear factor kappaB (NF-kappaB). The linear
      ubiquitination-specific deubiquitinase ovarian tumor domain deubiquitinase with
      linear linkage specificity (OTULIN) can control the immune signaling transduction
      pathway by restricting the Met1-linked ubiquitination process. In our study, the
      porcine OTLLIN gene was cloned and deubiquitin functions were detected in a
      porcine reproductive and respiratory syndrome virus (PRRSV)-infected-cell model.
      PRRSV infection promotes the expression of the OTULIN gene; in turn,
      overexpression of OTULIN contributes to PRRSV proliferation. There is negative
      regulation of innate immunity with OTULIN during viral infection. The cooperative
      effects of swine OTULIN and PRRSV Nsp11 potentiate the ability to reduce levels
      of cellular protein ubiquitin associated with innate immunity. Importantly, PRRSV
      Nsp11 recruits OTULIN through a nonenzymatic combination to enhance its ability
      to remove linear ubiquitination targeting NEMO, resulting in a superimposed
      effect that inhibits the production of type I interferons (IFNs). Our report
      presents a new model of virus utilization of the ubiquitin-protease system in
      vivo from the perspective of the viral proteins that interact with cell
      deubiquitination enzymes, providing new ideas for prevention and control of
      PRRSV.IMPORTANCE Deubiquitination effects of swine OTULIN were identified. The
      interaction between porcine OTULIN and PRRSV Nsp11 is dependent on the OTU
      domain. PRRSV Nsp11 recruits OTULIN through a nonenzymatic combination to promote
      removal of linear ubiquitination targeting NEMO, resulting in a superimposed
      effect that inhibits the production of type I IFNs.

PMID- 29444950
TI  - miRNA targeting and alternative splicing in the stress response - events hosted
      by membrane-less compartments.
AB  - Stress can be temporary or chronic, and mild or acute. Depending on its extent
      and severity, cells either alter their metabolism, and adopt a new state, or die.
      Fluctuations in environmental conditions occur frequently, and such stress
      disturbs cellular homeostasis, but in general, stresses are reversible and last
      only a short time. There is increasing evidence that regulation of gene
      expression in response to temporal stress happens post-transcriptionally in
      specialized subcellular membrane-less compartments called ribonucleoprotein (RNP)
      granules. RNP granules assemble through a concentration-dependent liquid-liquid
      phase separation of RNA-binding proteins that contain low-complexity sequence
      domains (LCDs). Interestingly, many factors that regulate microRNA (miRNA)
      biogenesis and alternative splicing are RNA-binding proteins that contain LCDs
      and localize to stress-induced liquid-like compartments. Consequently, gene
      silencing through miRNAs and alternative splicing of pre-mRNAs are emerging as
      crucial post-transcriptional mechanisms that function on a genome-wide scale to
      regulate the cellular stress response. In this Review, we describe the interplay
      between these two post-transcriptional processes that occur in liquid-like
      compartments as an adaptive cellular response to stress.

PMID- 29444949
TI  - Downregulation of MicroRNA eca-mir-128 in Seminal Exosomes and Enhanced
      Expression of CXCL16 in the Stallion Reproductive Tract Are Associated with Long
      Term Persistence of Equine Arteritis Virus.
AB  - Equine arteritis virus (EAV) can establish long-term persistent infection in the
      reproductive tract of stallions and is shed in the semen. Previous studies showed
      that long-term persistence is associated with a specific allele of the CXCL16
      gene (CXCL16S) and that persistent infection is maintained despite the presence
      of a local inflammatory and humoral and mucosal antibody responses. In this
      study, we demonstrated that equine seminal exosomes (SEs) are enriched in a small
      subset of microRNAs (miRNAs). Most importantly, we demonstrated that long-term
      EAV persistence is associated with the downregulation of an SE-associated miRNA
      (eca-mir-128) and with an enhanced expression of CXCL16 in the reproductive
      tract, a putative target of eca-mir-128. The findings presented here suggest that
      SE eca-mir-128 is implicated in the regulation of the CXCL16/CXCR6 axis in the
      reproductive tract of persistently infected stallions, a chemokine axis strongly
      implicated in EAV persistence. This is a novel finding and warrants further
      investigation to identify its specific mechanism in modulating the CXCL16/CXCR6
      axis in the reproductive tract of the EAV long-term carrier stallion.IMPORTANCE
      Equine arteritis virus (EAV) has the ability to establish long-term persistent
      infection in the stallion reproductive tract and to be shed in semen, which
      jeopardizes its worldwide control. Currently, the molecular mechanisms of viral
      persistence are being unraveled, and these are essential for the development of
      effective therapeutics to eliminate persistent infection. Recently, it has been
      determined that long-term persistence is associated with a specific allele of the
      CXCL16 gene (CXCL16S) and is maintained despite induction of local inflammatory,
      humoral, and mucosal antibody responses. This study demonstrated that long-term
      persistence is associated with the downregulation of seminal exosome miRNA eca
      mir-128 and enhanced expression of its putative target, CXCL16, in the
      reproductive tract. For the first time, this study suggests complex interactions
      between eca-mir-128 and cellular elements at the site of EAV persistence and
      implicates this miRNA in the regulation of the CXCL16/CXCR6 axis in the
      reproductive tract during long-term persistence.

PMID- 29444954
TI  - Invite your representative to work. Change the world. Here's how.
AB  - Today's political climate can seem hostile to science. Alternative facts, climate
      change denial, and relabeling of actual news as fake news are discouraging
      phenomena for sure. But these trends make it more important than ever to engage
      our politicians. Take heart! There is something you can do. You can show your
      representatives firsthand the amazing things you do, evidence of the economic
      engine that your activities generate, and the real people behind the discoveries.
      I did, and it was fun. We invited our congressman to the University of
      California, Santa Barbara (UCSB), and he accepted! For 2 hours, we explained and
      demonstrated efforts to cure blindness using stem cells, the medical implications
      of the discovery that cells can recover from the brink of death, a mosquito lab
      striving to eliminate insect-borne disease, and an Alzheimer's disease
      laboratory. Salud Carbajal peered through a microscope and met real scientists.
      Before his visit, he did not know what a postdoctoral fellow was, much less what
      stem cells look like. When he left he knew our names, how much money we bring
      into his district, and how important National Institutes of Health funding and
      international mobility are to our enterprise. Although I live in the United
      States, this approach should also apply to other democratic countries. If each of
      us converts one representative into a science champion, we can change the world.

PMID- 29444955
TI  - Common and divergent features of galactose-1-phosphate and fructose-1-phosphate
      toxicity in yeast.
AB  - Metabolic dysregulation leading to sugar-phosphate accumulation is toxic in
      organisms ranging from bacteria to humans. By comparing two models of sugar
      phosphate toxicity in Saccharomyces cerevisiae, we demonstrate that toxicity
      occurs, at least in part, through multiple, isomer-specific mechanisms, rather
      than a single general mechanism.

PMID- 29444956
TI  - Dual-color metal-induced and forster resonance energy transfer for cell
      nanoscopy.
AB  - We report a novel method, dual color axial nanometric localization by Metal
      Induced Energy Transfer (dcMIET), and combine it with Forster Resonant Energy
      Transfer (FRET) for resolving structural details in cells on the molecular level.
      We demonstrate the capability of this method on cytoskeletal elements and
      adhesions in human mesenchymal stem cells (hMSCs). Our approach is based on
      Fluorescence-Lifetime-Imaging Microscopy (FLIM), and allows for precise
      determination of the 3D architecture of stress fibers anchoring at focal
      adhesions, thus yielding crucial information to understand cell-matrix mechanics.
      In addition to resolving nanometric structural details along the z-axis, we use
      FRET to gain precise information on the distance between actin and vinculin at
      focal adhesions.

PMID- 29444953
TI  - Staphylococcal Osteomyelitis: Disease Progression, Treatment Challenges, and
      Future Directions.
AB  - Osteomyelitis is an inflammatory bone disease that is caused by an infecting
      microorganism and leads to progressive bone destruction and loss. The most common
      causative species are the usually commensal staphylococci, with Staphylococcus
      aureus and Staphylococcus epidermidis responsible for the majority of cases.
      Staphylococcal infections are becoming an increasing global concern, partially
      due to the resistance mechanisms developed by staphylococci to evade the host
      immune system and antibiotic treatment. In addition to the ability of
      staphylococci to withstand treatment, surgical intervention in an effort to
      remove necrotic and infected bone further exacerbates patient impairment. Despite
      the advances in current health care, osteomyelitis is now a major clinical
      challenge, with recurrent and persistent infections occurring in approximately
      40% of patients. This review aims to provide information about staphylococcus
      induced bone infection, covering the clinical presentation and diagnosis of
      osteomyelitis, pathophysiology and complications of osteomyelitis, and future
      avenues that are being explored to treat osteomyelitis.

PMID- 29444957
TI  - P38 activation induces the dissociation of tristetraprolin from Argonaute 2 to
      increase ARE-mRNA stabilization.
AB  - ARE-mRNAs are actively degraded with tristetraprolin (TTP) in resting cells while
      they turn into stable messengers in activated cells. P38 plays a crucial role in
      stabilizing ARE-mRNA. Here we reveal that P38 activation represses the
      interaction between TTP and Ago2, thus restraining TTP from being targeted into
      processing bodies and stabilizing ARE-mRNA.

PMID- 29444952
TI  - Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and
      Carbapenemase-Producing Enterobacteriaceae.
AB  - Therapy of invasive infections due to multidrug-resistant Enterobacteriaceae (MDR
      E) is challenging, and some of the few active drugs are not available in many
      countries. For extended-spectrum beta-lactamase and AmpC producers, carbapenems
      are the drugs of choice, but alternatives are needed because the rate of
      carbapenem resistance is rising. Potential active drugs include classic and newer
      beta-lactam-beta-lactamase inhibitor combinations, cephamycins, temocillin,
      aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or
      trimethoprim-sulfamethoxazole. These drugs might be considered in some specific
      situations. AmpC producers are resistant to cephamycins, but cefepime is an
      option. In the case of carbapenemase-producing Enterobacteriaceae (CPE), only
      some "second-line" drugs, such as polymyxins, tigecycline, aminoglycosides, and
      fosfomycin, may be active; double carbapenems can also be considered in specific
      situations. Combination therapy is associated with better outcomes for high-risk
      patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam
      was recently approved and is active against KPC and OXA-48 producers; the
      available experience is scarce but promising, although development of resistance
      is a concern. New drugs active against some CPE isolates are in different stages
      of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin,
      cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E
      infection must be individualized according to the susceptibility profile, type,
      and severity of infection and the features of the patient.

PMID- 29444958
TI  - Cdc48 and ubiquilins confer selective anterograde protein sorting and entry into
      the multivesicular body in yeast.
AB  - Cdc48/p97 and the ubiquilin family of UBA-UBL proteins are known for their role
      in the retrotranslocation of damaged proteins from the endoplasmic reticulum. We
      demonstrate that Cdc48 and the ubiquilin-like proteins in yeast also play a role
      in the anterograde trafficking of proteins, in this case the vacuolar protease,
      Cps1.

PMID- 29444959
TI  - The synaptotagmin C2B domain calcium-binding loops modulate the rate of fusion
      pore expansion.
AB  - In chromaffin cells, the kinetics of fusion pore expansion vary depending on
      which synaptotagmin isoform (Syt-1 or Syt-7) drives release. Our recent studies
      have shown that fusion pores of granules harboring Syt-1 expand more rapidly than
      those harboring Syt-7. Here, we sought to define the structural specificity of
      synaptotagmin action at the fusion pore by manipulating the Ca2+-binding C2B
      module. We generated a chimeric Syt-1 in which its C2B Ca2+-binding loops had
      been exchanged for those of Syt-7. Fusion pores of granules harboring a Syt-1 C2B
      chimera with all three Ca2+-binding loops of Syt-7 (Syt-1:7C2B123) exhibited
      slower rates of fusion pore expansion and neuropeptide cargo release relative to
      WT Syt-1. After fusion, this chimera also dispersed more slowly from fusion sites
      than WT protein. We speculate that the Syt-1:7 C2B123 and WT Syt-1 are likely to
      differ in their interactions with Ca2+ and membranes. Subsequent in vitro and in
      silico data demonstrated that the chimera exhibits a higher affinity for
      phospholipids than WT Syt-1. We conclude that the affinity of synaptotagmin for
      the plasma membrane, and the rate at which it releases the membrane, contribute
      in important ways to the rate of fusion pore expansion.

PMID- 29444960
TI  - Stent-assisted coil embolization on down-the-barrel view with spring-shaped
      microcatheter in patient with M1 ultrawide necked circumferential aneurysm.
AB  - Herein, we describe a technique for stent-assisted coil embolization with a
      spring-shaped microcatheter in a patient with an M1 ultrawide-necked
      circumferential aneurysm in the middle cerebral artery (MCA). A 49-year-old man
      was referred for treatment of an incidentally detected M1 large-circumference
      aneurysm on magnetic resonance angiography. Subsequent digital subtraction
      angiography revealed an 18.2*16.5 mm ultrawide-necked circumferential aneurysm on
      the distal M1 portion of the left MCA, and we planned stent-assisted coil
      embolization using a spring-shaped microcatheter. After we deployed the stent, we
      performed coil embolization under the down-the-barrel view by pulling out the
      microcatheter little by little. Using this technique, we could fill the coil mass
      evenly into the aneurysmal sac around the stent. And there were no immediate or
      delayed complications after the procedure. Stent-assisted coiling using a spring
      shaped microcatheter is a useful and safe technique for treating ultrawide-necked
      circumferential aneurysm or fusiform aneurysms.

PMID- 29444961
TI  - No inferiority of Tonbridge thrombectomy device for acute thrombus retrial
      compared with Solitaire device: an experimental evaluation with a canine distal
      external carotid-maxillary artery occlusion model.
AB  - INTRODUCTION: Mechanical thrombectomy (MT) has been widely accepted as a safe and
      effective treatment for acute ischemic stroke (AIS). Development of stent
      retriever devices has been intensively developed over the past two decades. In
      this study, we compared the effectiveness and safety of a new thrombectomy device
      with Solitaire FR for the treatment of AIS models. METHODS: Mechanical
      performance of stent retrievers was tested in vitro. Thrombin-induced thrombus
      was pre-injected into the right distal external carotid-maxillary artery in 18
      dogs to create an acute thrombus occlusion model, and these animals were divided
      into a Tonbridge group (n=9, with Tonbridge stent Tonbridge Medical Technology)
      and a Solitaire group as control (n=9, with Solitaire stent, ev3 Neurovascular).
      Final flow restoration, side branches, recanalization time, distal vessel
      embolism, and device-related complications were recorded and compared. A post
      procedure angiogram was obtained at 30 and 90 days after thrombectomy. Device
      manipulation-related damage to the arterial walls was evaluated histologically.
      RESULTS: In vitro test showed that the maximum friction within the microcatheter
      was 0.763 for the Tonbridge device and 0.784 n for the Solitaire (P>0.05). Slight
      increase in radial force was noticed for the Tonbridge (0.035 N/mm vs 0.031 N/mm
      of Solitaire, P>0.05). Eighteen and 16 retriever attempts were done in the
      Tonbridge (mean 2.0 attempts) and the Solitaire (mean 1.8 attempts) groups
      (P=0.74). The Tonbridge device led to good flow restoration in all nine (100%)
      models compared with eight (88.9%) in the Solitaire group (P=0.30). Side
      branches' influence (P=0.39), distal thromboembolism (P=0.60), and device-related
      complications (P=1.00) found no difference between the two groups. The rates of
      disruption of the internal elastic lamina (IEL) were 8.3% (2/24) and 4.2% (1/24)
      of the specimens, respectively (P=0.683). TICI 2b/3 flow of the right CCA were
      similar between the two groups at 1 (6/6 vs 6/6) and 3 months (6/6 vs 6/6) follow
      up (P>0.05). CONCLUSION: Our preliminary study indicated this new device was
      technically feasible and effective to be used in thrombectomy for the treatment
      of acute thrombus occlusion in canine models.

PMID- 29444962
TI  - Multiple anomalies in the origin and course of vertebral arteries and aberrant
      right subclavian artery in a child with moyamoya syndrome.
AB  - Here we report, for the first time, a combination of five-vessel aortic arch,
      anomalous origin of the right vertebral artery (VA) from the common carotid
      artery (CCA), an aberrant right subclavian artery (SCA), and bilateral
      symmetrical segmental agenesis of VAs.In this case report, we present a patient
      with moyamoya syndrome (MMS) and Down syndrome (DS) who has bilateral symmetrical
      segmental agenesis of VAs, left VA originating from aortic arch and anomalous
      origin of right VA arising from CCA in combination with an aberrant right SCA.
      Therefore, five vessels are originating from aortic arch. Here, we report, for
      the first time, a combination of five-vessel aortic arch with an aberrant right
      SCA and symmetrical segmental agenesis of both VAs. The possible embryological
      mechanisms of the anomalies as well as an relation with MMS and DS are discussed.

PMID- 29444963
TI  - Parapedicular vertebral augmentation with polymethylmetacrylate for pedicle screw
      loosening.
AB  - A 71-year-old man who had a L1/S1 posterior fusion revision surgery complained of
      increasing back pain 5 weeks after the open surgical procedure. The pain was
      initially estimated at 9/10 on the visual analog scale (VAS) and thought to be
      related to a right-sided L2 screw loosening. A right parapedicular vertebroplasty
      was performed and polymethylmethacrylate cement was instilled around the right
      pedicle screw, filling the anterior two-thirds of the vertebral body. On
      postvertebroplasty day 1, the patient had significant improvement in his low back
      pain. The pain further decreased at 1 and 3 months after the intervention (2/10
      on the VAS). Vertebroplasty is a minimally invasive, accessible, effective, and
      long lasting treatment for compression fractures. We believe that this technique
      could also be indicated to treat pain related to low grade screw loosening in
      properly selected patients.

PMID- 29444964
TI  - Electrical stimulation of the dorsolateral prefrontal cortex impairs semantic
      cognition.
AB  - OBJECTIVE: To identify the prefrontal cortical structures causally involved in
      verbal and nonverbal semantic cognition in both cerebral hemispheres. METHODS: We
      retrospectively screened the intraoperative brain mapping data of 584 patients
      who underwent neurosurgery for neoplastic tumor under local anesthesia with
      direct cortical electrostimulation. Patients were included if they were right
      handed, recently diagnosed with a diffuse low-grade glioma, and had a positive
      language mapping for verbal (naming task) and nonverbal (visual semantic
      association task) semantic cognition in the prefrontal cortex (n = 49). Among
      these, 30 were tested intraoperatively with both the naming and the semantic
      association tasks, while 19 were tested with the naming task only. Subsequently,
      each semantic site (n = 85) was plotted individually onto a common stereotaxic
      space for detailed analyses. RESULTS: The cortical sites associated with verbal
      semantic disturbances (n = 45) were distributed in the pars opercularis (n = 14)
      and pars triangularis (n = 19) of the left inferior frontal gyrus, and left
      dorsolateral prefrontal cortex (dlPFC, n = 12); only 2 sites were observed in the
      right dlPFC. In contrast, all but one cortical site associated with nonverbal
      semantic disturbances were observed in the left dorsolateral cortex (n = 8). In
      the right hemisphere, the same disturbances were found in the dlPFC (n = 14) and
      pars opercularis (n = 2). CONCLUSION: The present study demonstrated the critical
      role of the dlPFC in the semantic network, and indicated its specific and
      bilateral involvement in nonverbal semantic cognition in right-handers.

PMID- 29444965
TI  - Personalizing acute therapies for ischemic stroke: Thrombolysis or thrombectomy?

PMID- 29444967
TI  - Insights into atrial fibrillation newly diagnosed after stroke: Can the brain
      rule the heart?

PMID- 29444966
TI  - Cerebral microbleeds and CSF Alzheimer biomarkers in primary progressive
      aphasias.
AB  - OBJECTIVE: To reveal the prevalence and localization of cerebral microbleeds
      (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic,
      semantic, and nonfluent/agrammatic), to identify the relationship with underlying
      Alzheimer pathology, and to explore whether CMBs contribute to language
      breakdown. METHODS: We used a cross-sectional design in a multicenter cohort of
      82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for
      rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted
      imaging sequences) and white matter hyperintensities. CSF Alzheimer disease
      biomarker analyses available in 63 of the 82 patients provided the stratification
      of PPA into subgroups with patients who had or did not have probable underlying
      Alzheimer pathology. RESULTS: The prevalence of CMBs was higher in patients with
      PPA (28%) than in controls (16%). They were more prevalent in logopenic PPA (50%)
      than in semantic PPA (18%) and nonfluent/agrammatic PPA (17%). The localization
      of CMBs was mainly lobar (81%) with no difference between the PPA variants. CMBs
      were more frequent in PPA patients with positive than with negative CSF Alzheimer
      disease biomarkers (67% vs 20%). Patients with and without lobar CMBs had similar
      volumes of white matter hyperintensities. Language and general cognitive
      impairment in PPA was unrelated to CMB rates. CONCLUSIONS: CMB prevalence in PPA
      is higher than in healthy controls. CMBs were most prevalent in the logopenic
      variant, were related to underlying Alzheimer pathology, and did not affect the
      language/cognitive impairment. Our findings also suggest that CMB detection with
      MRI contributes to PPA variant diagnosis, especially of logopenic PPA, and
      provides an estimator of the underlying neuropathology.

PMID- 29444968
TI  - Behavioral interventions as a treatment for epilepsy: A multicenter randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the effect of a stress-reduction intervention in
      participants with medication-resistant epilepsy. METHODS: Adults with medication
      resistant focal epilepsy (n = 66) were recruited from 3 centers and randomized to
      1 of 2 interventions: (1) progressive muscle relaxation (PMR) with diaphragmatic
      breathing, or (2) control focused-attention activity with extremity movements.
      Following an 8-week baseline period, participants began 12 weeks of double-blind
      treatment. Daily self-reported mood and stress ratings plus seizure counts were
      completed by participants using an electronic diary, and no medication
      adjustments were permitted. The primary outcome was percent reduction in seizure
      frequency per 28 days comparing baseline and treatment; secondary outcomes
      included stress reduction and stress-seizure interaction. RESULTS: In the 66
      participants in the intention-to-treat analysis, seizure frequency was reduced
      from baseline in both treatment groups (PMR: 29%, p < 0.05; focused attention:
      25%, p < 0.05). PMR and focused attention did not differ in seizure reduction (p
      = 0.38), although PMR was associated with stress reduction relative to focused
      attention (p < 0.05). Daily stress was not a predictor of seizures. CONCLUSIONS:
      Both PMR and the focused-attention groups showed reduced seizure frequency
      compared to baseline in participants with medication-resistant focal seizures,
      although the 2 treatments did not differ. PMR was more effective than focused
      attention in reducing self-reported stress. CLINICALTRIALSGOV IDENTIFIER:
      NCT01444183.

PMID- 29444970
TI  - Cytoplasmic RNA granules, ribostasis, and neurodegeneration.

PMID- 29444969
TI  - Atrial fibrillation detected after stroke is related to a low risk of ischemic
      stroke recurrence.
AB  - OBJECTIVE: To compare the risk of 1-year ischemic stroke recurrence between
      atrial fibrillation (AF) diagnosed after stroke (AFDAS) and sinus rhythm (SR) and
      investigate whether underlying heart disease is as frequent in AFDAS as it is in
      AF known before stroke (KAF). METHODS: In this retrospective cohort study, we
      included all ischemic stroke patients admitted to institutions participating in
      the Ontario Stroke Registry from July 1, 2003, to March 31, 2013. Based on heart
      rhythm assessed during admission, we classified patients as AFDAS, KAF, or SR. We
      modeled the relationship between heart rhythm groups and 1-year ischemic stroke
      recurrence by using Cox regression adjusted for multiple covariates (e.g., oral
      anticoagulants). We compared the prevalence of coronary artery disease,
      myocardial infarction, and heart failure among the 3 groups. RESULTS: Among
      23,376 ischemic stroke patients, 15,885 had SR, 587 AFDAS, and 6,904 KAF. At 1
      year, 39 (6.6%) patients with AFDAS, 661 (9.6%) with KAF, and 1,269 (8.0%) with
      SR had recurrent ischemic strokes (p = 0.0001). AFDAS-related ischemic stroke
      recurrence adjusted risk was not different from that of SR (hazard ratio 0.90
      [95% confidence interval 0.63, 1.30]; p = 0.57). Prevalence of coronary artery
      disease (18.2% vs 34.7%; p < 0.0001), myocardial infarction (11.6% vs 20.5%; p <
      0.0001), and heart failure (5.5% vs 16.8%; p < 0.0001) were lower in AFDAS
      relative to KAF. CONCLUSIONS: The lack of difference in 1-year ischemic stroke
      recurrence between AFDAS and SR and the lower prevalence of heart disease in
      AFDAS compared to KAF suggest that the underlying pathophysiology of AFDAS may
      differ from that of KAF.

PMID- 29444971
TI  - Anosognosia predicts default mode network hypometabolism and clinical progression
      to dementia.
AB  - OBJECTIVE: To identify the pathophysiologic mechanisms and clinical significance
      of anosognosia for cognitive decline in mild cognitive impairment. METHODS: We
      stratified 468 patients with amnestic mild cognitive impairment into intact and
      impaired awareness groups, determined by the discrepancy between the patient and
      the informant score on the Everyday Cognition questionnaire. Voxel-based linear
      regression models evaluated the associations between self-awareness status and
      baseline beta-amyloid load, measured by [18F]florbetapir, and the relationships
      between awareness status and regional brain glucose metabolism measured by
      [18F]fluorodeoxyglucose at baseline and at 24-month follow-up. Multivariate
      logistic regression tested the association of awareness status with conversion
      from amnestic mild cognitive impairment to dementia. RESULTS: We found that
      participants with impaired awareness had lower [18F]fluorodeoxyglucose uptake and
      increased [18F]florbetapir uptake in the posterior cingulate cortex at baseline.
      In addition, impaired awareness in mild cognitive impairment predicted
      [18F]fluorodeoxyglucose hypometabolism in the posterior cingulate cortex, left
      basal forebrain, bilateral medial temporal lobes, and right lateral temporal lobe
      over 24 months. Furthermore, participants with impaired awareness had a nearly 3
      fold increase in likelihood of conversion to dementia within a 2-year time frame.
      CONCLUSIONS: Our results suggest that anosognosia is linked to Alzheimer disease
      pathophysiology in vulnerable structures, and predicts subsequent hypometabolism
      in the default mode network, accompanied by an increased risk of progression to
      dementia. This highlights the importance of assessing awareness of cognitive
      decline in the clinical evaluation and management of individuals with amnestic
      mild cognitive impairment.

PMID- 29444972
TI  - Usefulness of ADAMTS13 to predict response to recanalization therapies in acute
      ischemic stroke.
AB  - OBJECTIVE: We aimed to analyze ADAMTS13 (a disintegrin and metalloproteinase with
      a thrombospondin type 1 motif, member 13) in relation to arterial recanalization
      in patients treated with IV tissue plasminogen activator (tPA) and in relation to
      futile recanalization in patients treated with mechanical thrombectomy. METHODS:
      Acute ischemic stroke patients (n = 108) with documented arterial occlusions
      treated with IV-tPA were selected. ADAMTS13 activity was measured by ELISA in
      samples collected before treatment. Recanalization was assessed at 2 hours by
      transcranial Doppler. In 78 consecutive patients treated with endovascular
      thrombectomy, ADAMTS13 antigen was measured by ELISA and futile recanalization
      was defined as complete recanalization plus modified Rankin Scale score >2 at 3
      months. Independent predictors of recanalization and futile recanalization were
      determined by logistic regression, adjusted by age, NIH Stroke Scale score, and
      time from stroke onset. RESULTS: Patients who achieved tPA-induced recanalization
      had higher baseline ADAMTS13 activity (78.1% [68%-88%] vs 70.1% [61%-79%], p =
      0.021). In logistic regression analysis, ADAMTS13 activity >75% was an
      independent predictor of recanalization (odds ratio = 6.76 [1.52-30.02], p =
      0.012), together with absence of early ischemic signs and Oxfordshire Community
      Stroke Project classification. Regarding endovascular therapies, a reduced
      ADAMTS13 concentration (<982 ng/mL) was an independent predictor of futile
      recanalization (odds ratio = 67.4 [1.4-3,282.1], p = 0.034), together with age
      and diabetes mellitus. The addition of ADAMTS13 to clinical predictors of tPA
      induced recanalization and futile recanalization improved discrimination and
      reclassification (integrated discrimination improvement = 10.06% and 28.4%, net
      reclassification improvement = 61.0% and 107.4%, respectively). CONCLUSIONS: A
      reduced ADAMTS13 was associated with poor response to recanalization therapies.
      If confirmed in future prospective studies, a panel of blood biomarkers including
      ADAMTS13 might be a useful tool to guide reperfusion therapies.

PMID- 29444973
TI  - Eight-hours adaptive deep brain stimulation in patients with Parkinson disease.
AB  - OBJECTIVES: To assess the feasibility and clinical efficacy of local field
      potentials (LFPs)-based adaptive deep brain stimulation (aDBS) in patients with
      advanced Parkinson disease (PD) during daily activities in an open-label,
      nonblinded study. METHODS: We monitored neurophysiologic and clinical
      fluctuations during 2 perioperative experimental sessions lasting for up to 8
      hours. On the first day, the patient took his/her daily medication, while on the
      second, he/she additionally underwent subthalamic nucleus aDBS driven by LFPs
      beta band power. RESULTS: The beta band power correlated in both experimental
      sessions with the patient's clinical state (Pearson correlation coefficient r =
      0.506, p < 0.001, and r = 0.477, p < 0.001). aDBS after LFP changes was effective
      (30% improvement without medication [3-way analysis of variance, interaction day
      * medication p = 0.036; 30.5 +/- 3.4 vs 22.2 +/- 3.3, p = 0.003]), safe, and well
      tolerated in patients performing regular daily activities and taking additional
      dopaminergic medication. aDBS was able to decrease DBS amplitude during motor
      "on" states compared to "off" states (paired t test p = 0.046), and this
      automatic adjustment of STN-DBS prevented dyskinesias. CONCLUSIONS: The main
      findings of our study are that aDBS is technically feasible in everyday life and
      provides a safe, well-tolerated, and effective treatment method for the
      management of clinical fluctuations. CLASSIFICATION OF EVIDENCE: This study
      provides Class IV evidence that for patients with advanced PD, aDBS is safe, well
      tolerated, and effective in controlling PD motor symptoms.

PMID- 29444974
TI  - A 35-year analysis of sex differences in neurology authorship.
AB  - Career progression in academic medicine is partly influenced by publication
      productivity. There has been a significant increase in female authorship over a
      35-year time period at both the first and senior authorship positions in 3 high
      impact factor neurology journals in the United States. While these trends are
      encouraging, a sex gap remains. Institutions/departments may wish to consider
      further strategies for trainees and faculty that can help to maintain momentum
      and narrow the gap further.

PMID- 29444975
TI  - Approaching adaptive control in neurostimulation for Parkinson disease: Autopilot
      on.

PMID- 29444976
TI  - FoxO transcription factors modulate autophagy and proteoglycan 4 in cartilage
      homeostasis and osteoarthritis.
AB  - Aging is a main risk factor for osteoarthritis (OA). FoxO transcription factors
      protect against cellular and organismal aging, and FoxO expression in cartilage
      is reduced with aging and in OA. To investigate the role of FoxO in cartilage,
      Col2Cre-FoxO1, 3, and 4 single knockout (KO) and triple KO mice (Col2Cre-TKO)
      were analyzed. Articular cartilage in Col2Cre-TKO and Col2Cre-FoxO1 KO mice was
      thicker than in control mice at 1 or 2 months of age. This was associated with
      increased proliferation of chondrocytes of Col2Cre-TKO mice in vivo and in vitro.
      OA-like changes developed in cartilage, synovium, and subchondral bone between 4
      and 6 months of age in Col2Cre-TKO and Col2Cre-FoxO1 KO mice. Col2Cre-FoxO3 and
      FoxO4 KO mice showed no cartilage abnormalities until 18 months of age when
      Col2Cre-FoxO3 KO mice had more severe OA than control mice. Autophagy and
      antioxidant defense genes were reduced in Col2Cre-TKO mice. Deletion of FoxO1/3/4
      in mature mice using Aggrecan(Acan)-CreERT2 (AcanCreERT-TKO) also led to
      spontaneous cartilage degradation and increased OA severity in a surgical model
      or treadmill running. The superficial zone of knee articular cartilage of Col2Cre
      TKO and AcanCreERT-TKO mice exhibited reduced cell density and markedly decreased
      Prg4 In vitro, ectopic FoxO1 expression increased Prg4 and synergized with
      transforming growth factor-beta stimulation. In OA chondrocytes, overexpression
      of FoxO1 reduced inflammatory mediators and cartilage-degrading enzymes,
      increased protective genes, and antagonized interleukin-1beta effects. Our
      observations suggest that FoxO play a key role in postnatal cartilage
      development, maturation, and homeostasis and protect against OA-associated
      cartilage damage.

PMID- 29444978
TI  - An off-target effect of BX795 blocks herpes simplex virus type 1 infection of the
      eye.
AB  - Herpes simplex virus type 1 (HSV-1) causes recurrent mucocutaneous lesions in the
      eye that may advance to corneal blindness. Nucleoside analogs exemplified by
      acyclovir (ACV) form the primary class of antiherpetic drugs, but this class
      suffers limitations due to the emergence of viral resistance and other side
      effects. While studying the molecular basis of ocular HSV-1 infection, we
      observed that BX795, a commonly used inhibitor of TANK-binding kinase 1 (TBK1),
      strongly suppressed infection by multiple strains of HSV-1 in transformed and
      primary human cells, cultured human and animal corneas, and a murine model of
      ocular infection. Our investigations revealed that the antiviral activity of
      BX795 relies on targeting Akt phosphorylation in infected cells, leading to the
      blockage of viral protein synthesis. This small-molecule inhibitor, which was
      also effective against an ACV-resistant HSV-1 strain, shows promise as an
      alternative to existing drugs and as an effective topical therapy for ocular
      herpes infection. Collectively, our results obtained using multiple infection
      models and virus strains establish BX795 as a promising lead compound for broad
      spectrum antiviral applications in humans.

PMID- 29444977
TI  - Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic
      lymphocytic leukemia indolence.
AB  - Although the progression of chronic lymphocytic leukemia (CLL) requires the
      cooperation of the microenvironment, the exact cellular and molecular mechanisms
      involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL
      23R)/IL-23 axis and found that circulating cells from early-stage CLL patients
      with shorter time-to-treatment, but not of those with a more benign course,
      expressed a defective form of the IL-23R complex lacking the IL-12Rbeta1 chain.
      However, cells from both patient groups expressed the complete IL-23R complex in
      tissue infiltrates and could be induced to express the IL-12Rbeta1 chain when
      cocultured with activated T cells or CD40L+ cells. CLL cells activated in vitro
      in this context produced IL-23, a finding that, together with the presence of IL
      23 in CLL lymphoid tissues, suggests the existence of an autocrine/paracrine loop
      inducing CLL cell proliferation. Interference with the IL-23R/IL-23 axis using an
      anti-IL-23p19 antibody proved effective in controlling disease onset and
      expansion in xenografted mice, suggesting potential therapeutic strategies.

PMID- 29444979
TI  - Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic
      basis for anticancer therapy.
AB  - Cancer cells adapt to their inherently increased oxidative stress through
      activation of the glutathione (GSH) and thioredoxin (TXN) systems. Inhibition of
      both of these systems effectively kills cancer cells, but such broad inhibition
      of antioxidant activity also kills normal cells, which is highly unwanted in a
      clinical setting. We therefore evaluated targeting of the TXN pathway alone and,
      more specifically, selective inhibition of the cytosolic selenocysteine
      containing enzyme TXN reductase 1 (TXNRD1). TXNRD1 inhibitors were discovered in
      a large screening effort and displayed increased specificity compared to pan
      TXNRD inhibitors, such as auranofin, that also inhibit the mitochondrial enzyme
      TXNRD2 and additional targets. For our lead compounds, TXNRD1 inhibition
      correlated with cancer cell cytotoxicity, and inhibitor-triggered conversion of
      TXNRD1 from an antioxidant to a pro-oxidant enzyme correlated with corresponding
      increases in cellular production of H2O2 In mice, the most specific TXNRD1
      inhibitor, here described as TXNRD1 inhibitor 1 (TRi-1), impaired growth and
      viability of human tumor xenografts and syngeneic mouse tumors while having
      little mitochondrial toxicity and being better tolerated than auranofin. These
      results display the therapeutic anticancer potential of irreversibly targeting
      cytosolic TXNRD1 using small molecules and present potent and selective TXNRD1
      inhibitors. Given the pronounced up-regulation of TXNRD1 in several metastatic
      malignancies, it seems worthwhile to further explore the potential benefit of
      specific irreversible TXNRD1 inhibitors for anticancer therapy.

PMID- 29444980
TI  - Circulating TFH cells, serological memory, and tissue compartmentalization shape
      human influenza-specific B cell immunity.
AB  - Immunization with the inactivated influenza vaccine (IIV) remains the most
      effective strategy to combat seasonal influenza infections. IIV activates B cells
      and T follicular helper (TFH) cells and thus engenders antibody-secreting cells
      and serum antibody titers. However, the cellular events preceding generation of
      protective immunity in humans are inadequately understood. We undertook an in
      depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults.
      Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype,
      and isotype of influenza-specific B cells against A/California09-H1N1,
      A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three
      pronged B cell response comprising a transient CXCR5-CXCR3+ antibody-secreting B
      cell population, CD21hiCD27+ memory B cells, and CD21loCD27+ B cells. Activation
      of circulating TFH cells correlated with the development of both CD21lo and
      CD21hi memory B cells. However, preexisting antibodies could limit increases in
      serum antibody titers. IIV had no marked effect on CD8+, mucosal-associated
      invariant T, gammadelta T, and natural killer cell activation. In addition,
      vaccine-induced B cells were not maintained in peripheral blood at 1 year after
      vaccination. We provide a dissection of rHA-specific B cells across seven human
      tissue compartments, showing that influenza-specific memory (CD21hiCD27+) B cells
      primarily reside within secondary lymphoid tissues and the lungs. Our study
      suggests that a rational design of universal vaccines needs to consider
      circulating TFH cells, preexisting serological memory, and tissue
      compartmentalization for effective B cell immunity, as well as to improve
      targeting cellular T cell immunity.

PMID- 29444982
TI  - The unique features of proteins depicting the chicken amniotic fluid.
AB  - In many amniotes, the amniotic fluid is depicted as a dynamic milieu that
      participates in the protection of the embryo (cushioning, hydration, and
      immunity). However, in birds, the protein profile of the amniotic fluid remains
      unexplored, even though its proteomic signature is predicted to differ compared
      to human's. In fact, unlike humans, chicken amniotic fluid does not collect
      excretory products and its protein composition strikingly changes at mid
      development due to the massive inflow of egg white proteins, which are thereafter
      swallowed by the embryo to support its growth. Using GeLC-MS/MS and shotgun
      strategies, we identified 91 non-redundant proteins delineating the chicken
      amniotic fluid proteome at day 11 of development, before egg white transfer.
      These proteins were essentially associated with the metabolism of nutrients,
      immune response and developmental processes. Forty-eight proteins were common to
      both chicken and human amniotic fluids, including serum albumin, apolipoprotein
      A1 and alpha-fetoprotein. We further investigated the effective role of the
      chicken amniotic fluid in innate defense and revealed that it exhibits
      significant antibacterial activity at day 11 of development. This antibacterial
      potential is drastically enhanced after egg white transfer, presumably due to
      lysozyme, avian beta-defensin 11, vitelline membrane outer layer protein 1, and
      beta-microseminoprotein-like as the most likely antibacterial candidates.
      Interestingly, several proteins recovered in the chicken amniotic fluid prior and
      after egg white transfer are uniquely found in birds (ovalbumin and related
      proteins X and Y, avian beta-defensin 11) or oviparous species (vitellogenins 1
      and 2, riboflavin-binding protein). This study provides an integrative overview
      of the chicken amniotic fluid proteome and opens stimulating perspectives in
      deciphering the role of the avian egg-specific proteins in embryonic development,
      including innate immunity. These proteins may constitute valuable biomarkers for
      poultry production to detect hazardous situations (stress, infection, etc.), that
      may negatively affect the development of the chicken embryo.

PMID- 29444981
TI  - Protein Palmitoylation Plays an Important Role in Trichomonas vaginalis
      Adherence.
AB  - The flagellated protozoan parasite Trichomonas vaginalis is the etiologic agent
      of trichomoniasis, the most common non-viral sexually transmitted infection
      worldwide. As an obligate extracellular pathogen, adherence to epithelial cells
      is critical for parasite survival within the human host and a better
      understanding of this process is a prerequisite for the development of therapies
      to combat infection. In this sense, recent work has shown S-acylation as a key
      modification that regulates pathogenesis in different protozoan parasites.
      However, there are no reports indicating whether this post-translational
      modification is a mechanism operating in T. vaginalis In order to study the
      extent and function of S-acylation in T. vaginalis biology, we undertook a
      proteomic study to profile the full scope of S-acylated proteins in this parasite
      and reported the identification of 363 proteins involved in a variety of
      biological processes such as protein transport, pathogenesis related and
      signaling, among others. Importantly, treatment of parasites with the
      palmitoylation inhibitor 2-bromopalmitate causes a significant decrease in
      parasite: parasite aggregation as well as adherence to host cells suggesting that
      palmitoylation could be modifying proteins that are key regulators of Trichomonas
      vaginalis pathogenesis.

PMID- 29444983
TI  - Working with Schemas, Predicting with Schemas.

PMID- 29444984
TI  - Guiding policy to reduce the burden of COPD: the role of epidemiological
      research.

PMID- 29444985
TI  - Molecular Pharmacodynamics-Guided Scheduling of Biologically Effective Doses: A
      Drug Development Paradigm Applied to MET Tyrosine Kinase Inhibitors.
AB  - The development of molecularly targeted agents has benefited from use of
      pharmacodynamic markers to identify "biologically effective doses" (BED) below
      MTDs, yet this knowledge remains underutilized in selecting dosage regimens and
      in comparing the effectiveness of targeted agents within a class. We sought to
      establish preclinical proof-of-concept for such pharmacodynamics-based BED
      regimens and effectiveness comparisons using MET kinase small-molecule
      inhibitors. Utilizing pharmacodynamic biomarker measurements of MET signaling
      (tumor pY1234/1235MET/total MET ratio) in a phase 0-like preclinical setting, we
      developed optimal dosage regimens for several MET kinase inhibitors and compared
      their antitumor efficacy in a MET-amplified gastric cancer xenograft model (SNU
      5). Reductions in tumor pY1234/1235MET/total MET of 95%-99% were achievable with
      tolerable doses of EMD1214063/MSC2156119J (tepotinib), XL184 (cabozantinib), and
      XL880/GSK1363089 (foretinib), but not ARQ197 (tivantinib), which did not alter
      the pharmacodynamic biomarker. Duration of kinase suppression and rate of kinase
      recovery were specific to each agent, emphasizing the importance of developing
      customized dosage regimens to achieve continuous suppression of the
      pharmacodynamic biomarker at the required level (here, >=90% MET kinase
      suppression). The customized dosage regimen of each inhibitor yielded substantial
      and sustained tumor regression; the equivalent effectiveness of customized dosage
      regimens that achieve the same level of continuous molecular target control
      represents preclinical proof-of-concept and illustrates the importance of proper
      scheduling of targeted agent BEDs. Pharmacodynamics-guided biologically effective
      dosage regimens (PD-BEDR) potentially offer a superior alternative to
      pharmacokinetic guidance (e.g., drug concentrations in surrogate tissues) for
      developing and making head-to-head comparisons of targeted agents. Mol Cancer
      Ther; 17(3); 698-709. (c)2018 AACR.

PMID- 29444986
TI  - British Thoracic Society Guideline for the investigation and management of
      malignant pleural mesothelioma.

PMID- 29444987
TI  - Cardiovascular Risk Prediction Functions Underestimate Risk in HIV Infection.
AB  - BACKGROUND: Cardiovascular disease (CVD) risk is elevated in HIV-infected
      individuals, with contributions from both traditional and nontraditional risk
      factors. The accuracy of established CVD risk prediction functions in HIV is
      uncertain. We sought to assess the performance of 3 established CVD risk
      prediction functions in a longitudinal cohort of HIV-infected men. METHODS: The
      FHS (Framingham Heart Study) functions for hard coronary heart disease (FHS CHD)
      and atherosclerotic CVD (FHS ASCVD) and the American College of
      Cardiology/American Heart Association ASCVD function were applied to the Partners
      HIV cohort. Risk scores were calculated between January 1, 2006, and December 31,
      2008. Outcomes included CHD (myocardial infarction or coronary death) for the FHS
      CHD function and ASCVD (myocardial infarction, stroke, or coronary death) for the
      FHS ASCVD and American College of Cardiology/American Heart Association ASCVD
      functions. We investigated the accuracy of CVD risk prediction for each function
      when applied to the HIV cohort using comparison of Cox regression coefficients,
      discrimination, and calibration. RESULTS: The HIV cohort was comprised of 1272
      men followed for a median of 4.4 years. There were 78 (6.1%) ASCVD events; the 5
      year incidence rate was 16.4 per 1000 person-years. Discrimination was moderate
      to poor as indicated by the low c statistic (0.68 for FHS CHD, 0.65 for American
      College of Cardiology/American Heart Association ASCVD, and 0.67 for FHS ASCVD).
      Observed CVD risk exceeded the predicted risk for each of the functions in most
      deciles of predicted risk. Calibration, or goodness of fit of the models, was
      consistently poor, with significant chi2P values for all functions. Recalibration
      did not significantly improve model fit. CONCLUSIONS: Cardiovascular risk
      prediction functions developed for use in the general population are inaccurate
      in HIV infection and systematically underestimate risk in a cohort of HIV
      infected men. Development of tailored CVD risk prediction functions incorporating
      traditional CVD risk factors and HIV-specific factors is likely to result in more
      accurate risk estimation to guide preventative CVD care.

PMID- 29444989
TI  - Introducing the new BTS guideline: the investigation and management of pleural
      malignant mesothelioma.

PMID- 29444988
TI  - NMDA-Type Glutamate Receptor Activation Promotes Vascular Remodeling and
      Pulmonary Arterial Hypertension.
AB  - BACKGROUND: Excessive proliferation and apoptosis resistance in pulmonary
      vascular cells underlie vascular remodeling in pulmonary arterial hypertension
      (PAH). Specific treatments for PAH exist, mostly targeting endothelial
      dysfunction, but high pulmonary arterial pressure still causes heart failure and
      death. Pulmonary vascular remodeling may be driven by metabolic reprogramming of
      vascular cells to increase glutaminolysis and glutamate production. The N-methyl
      d-aspartate receptor (NMDAR), a major neuronal glutamate receptor, is also
      expressed on vascular cells, but its role in PAH is unknown. METHODS: We assessed
      the status of the glutamate-NMDAR axis in the pulmonary arteries of patients with
      PAH and controls through mass spectrometry imaging, Western blotting, and
      immunohistochemistry. We measured the glutamate release from cultured pulmonary
      vascular cells using enzymatic assays and analyzed NMDAR
      regulation/phosphorylation through Western blot experiments. The effect of NMDAR
      blockade on human pulmonary arterial smooth muscle cell proliferation was
      determined using a BrdU incorporation assay. We assessed the role of NMDARs in
      vascular remodeling associated to pulmonary hypertension, in both smooth muscle
      specific NMDAR knockout mice exposed to chronic hypoxia and the monocrotaline rat
      model of pulmonary hypertension using NMDAR blockers. RESULTS: We report
      glutamate accumulation, upregulation of the NMDAR, and NMDAR engagement reflected
      by increases in GluN1-subunit phosphorylation in the pulmonary arteries of human
      patients with PAH. Kv channel inhibition and type A-selective endothelin receptor
      activation amplified calcium-dependent glutamate release from human pulmonary
      arterial smooth muscle cell, and type A-selective endothelin receptor and
      platelet-derived growth factor receptor activation led to NMDAR engagement,
      highlighting crosstalk between the glutamate-NMDAR axis and major PAH-associated
      pathways. The platelet-derived growth factor-BB-induced proliferation of human
      pulmonary arterial smooth muscle cells involved NMDAR activation and
      phosphorylated GluN1 subunit localization to cell-cell contacts, consistent with
      glutamatergic communication between proliferating human pulmonary arterial smooth
      muscle cells via NMDARs. Smooth-muscle NMDAR deficiency in mice attenuated the
      vascular remodeling triggered by chronic hypoxia, highlighting the role of
      vascular NMDARs in pulmonary hypertension. Pharmacological NMDAR blockade in the
      monocrotaline rat model of pulmonary hypertension had beneficial effects on
      cardiac and vascular remodeling, decreasing endothelial dysfunction, cell
      proliferation, and apoptosis resistance while disrupting the glutamate-NMDAR
      pathway in pulmonary arteries. CONCLUSIONS: These results reveal a dysregulation
      of the glutamate-NMDAR axis in the pulmonary arteries of patients with PAH and
      identify vascular NMDARs as targets for antiremodeling treatments in PAH.

PMID- 29444991
TI  - Ozone Generation during High-Voltage Leak Detection: Fiction or Reality?
AB  - In order to further clarify if and how much ozone is generated during high
      voltage leak detection and to identify measures to reduce the impact of ozone
      generation on product quality, a highly sensitive analytical system was employed
      to investigate the generation of ozone at different operational conditions of
      high-voltage leak detection integrity testing. The analytical system is based on
      oxidation of Iodide ions in solution and identification of the Iodine formed by
      N, N-Diethyl-p-phenylendiamine (DPD) according to DIN 38403. Sensitivity of the
      system was found suitable to detect ozone levels as low as 0.025 ppm (mg/L). High
      voltage leak detection process parameters-inspection speed, high voltage, filling
      level of the ampoule, and exposure time to the ampoule to high voltage-were
      varied between maximum and minimum values applicable in integrity testing of
      different ampoule sizes. For variation of exposure time, ampoules were
      repetitively tested by the leak testing machine to achieve a maximum exposure
      time of the ampoule up to 24 s (exposure time during production <=2.4 s). No
      ozone was detected during the study under all inspection conditions. Even
      repeated exposure of the ampoules to high-voltage leak detection did not result
      in generation of measurable ozone levels. It has to be concluded that high
      voltage leak detection is not prone to causing oxidation of the drug products.LAY
      ABSTRACT: For drug products in ampoules, 100% integrity testing is requested both
      by European and US regulations. Detection of integrity defects like small holes
      or cracks in the ampoule can be performed by numerous methods. Due to automation
      requirements, only three methods have been used during routine production-vacuum
      decay, head space infrared spectroscopy, and high-voltage leak detection. High
      voltage leak detection is the most common method used in the pharmaceutical
      industry for 100% integrity testing of ampoules, but resent publications showed
      considerable oxidation of an air-sensitive active pharmaceutical ingredient
      during the integrity testing process. It was assumed that ozone generated in the
      inside of the vial due to exposure of the product to the high voltage during the
      testing process may be responsible for this result. As ozone is a very aggressive
      and non-selective oxidant, this result posed a serious thread not only to this
      product but also to the quality of many other products subjected to integrity
      testing by high-voltage leak detection.

PMID- 29444992
TI  - Microbiological Control for Affinity Capture Chromatography Processing: An
      Industry Perspective.
AB  - The purpose of this paper is to provide a summary of a BPOG-led industry survey
      of the microbiological control aspects of affinity chromatography processing in
      the biopharmaceutical industry. The document provides a summary of historical
      microbiological control concerns, coupled with industry-derived best practices,
      for material, equipment, and storage controls required to mitigate the potential
      for microbial ingress and contamination of chromatography resin and equipment.
      These best practice guidelines, which are derived from the members of the BPOG
      Bioburden Working Group, are intended to assist biopharmaceutical manufacturers
      to enhance microbial control and monitoring strategies for chromatography
      systems.

PMID- 29444993
TI  - A Novel Method for Qualification of a Potency Assay through Partial Computer
      Simulation.
AB  - For biotherapeutics and vaccines, potency is measured in a bioassay that compares
      the concentration-response curves of a new batch to that of a reference standard.
      Acceptable accuracy and precision of potency measurement is critical to the
      manufacturing of these products. These characteristics of a bioassay are
      typically assessed in a procedure that is carried out with samples spanning the
      acceptable range for the product. During early development, however, a full
      validation study such as that which is carried out in late development can be
      costly as it relates to the likelihood of eventual program success. For these
      reasons, the laboratory may look for alternative ways to ensure the validity of
      the bioassay across a range that will support product development. One such
      alternative combines information from a reduced procedure using only reference
      standard and 100% relative potency concentration-response data sets, together
      with computer simulation, to estimate missing relative potency values across the
      desired range. Fits to the reduced dataset provide estimates of bioassay model
      parameters such as those for an S-shaped potency assay that follows a four
      parameter logistic relationship, along with estimates of their variance
      covariance structure and independent experimental unit (e.g., well-to-well or
      animal-to-animal) errors. Using Bayesian Markov Chain Monte Carlo modeling, the
      predictive distribution of the concentration-response data for the desired levels
      of relative potency is generated. Results from use of the reduced procedure are
      compared to results calculated from a full dataset in Monte Carlo simulation and
      in a motivating example.LAY ABSTRACT: For biotherapeutics and vaccines, potency
      is measured in a bioassay that compares the concentration-response curves of a
      new batch to that of a reference standard. Acceptable accuracy and precision of
      potency measurement is critical to the manufacturing of these products. These
      characteristics of a bioassay are typically assessed in a procedure that is
      carried out with samples spanning the acceptable range for the product. During
      early development, however, a full validation study such as that which is carried
      out in late development can be costly as it relates to the likelihood of eventual
      program success. For these reasons, the laboratory may look for alternative ways
      to ensure the validity of the bioassay across a range that will support product
      development. One such alternative combines information from a reduced procedure
      using only reference standard and 100% relative potency concentration-response
      data sets, together with computer simulation, to estimate missing relative
      potency values across the desired range. Bayesian Markov Chain Monte Carlo
      modeling is used to generate the distributions of the missing potency levels.
      Results from use of the reduced procedure are compared to results calculated from
      a full dataset in Monte Carlo simulation and in a motivating example.

PMID- 29444994
TI  - Life Cycle Assessment of Reusable and Disposable Cleanroom Coveralls.
AB  - Cleanroom garments serve a critical role in such industries as pharmaceuticals,
      life sciences, and semiconductor manufacturing. These textiles are available in
      reusable and disposable alternatives. In this report, the environmental
      sustainability of cleanroom coveralls is examined using life cycle assessment
      technology. The complete supply chain, manufacture, use, and end-of-life phases
      for reusable and disposable cleanroom coveralls are compared on a cradle-to-end
      of-life cycle basis. Three industry representative coveralls are examined: a
      reusable woven polyethylene terephthalate (PET) coverall, a disposable flash
      spunbonded high-density polyethylene (HDPE) coverall, and a disposable spunbond
      meltblown-spunbond polypropylene (SMS PP) coverall. The reusable cleanroom
      coverall system shows substantial improvements over both disposable cleanroom
      coverall systems in all environmental impact categories. The improvements over
      the disposable HDPE coverall were 34% lower process energy (PE), 23% lower
      natural resource energy (NRE), 27% lower greenhouse gas (GHG) emissions, and 73%
      lower blue water consumption. The improvements over the disposable SMS PP
      coverall were 59% lower PE, 56% lower NRE, 57% lower GHG emissions, and 77% lower
      blue water consumption. In addition, the reusable system shows a 94-96% reduction
      in solid waste to the landfill from the cleanroom facility. Between the two
      disposable cleanroom coveralls, the flash spunbonded HDPE coverall shows a
      measurable environmental improvement over the SMS PP coverall.LAY ABSTRACT:
      Pharmaceutical drugs are manufactured and handled in controlled environments
      called cleanrooms to ensure the safety and quality of products. In order to
      maintain strict levels of cleanliness, cleanroom personnel are required to wear
      garments such as coveralls, hoods, and gloves that restrict the transfer of
      particles from the person to the environment. These garments are available in
      reusable and disposable types. Cleanroom operators consider a number of factors
      when selecting between reusable and disposable garments, including price,
      comfort, and environmental sustainability.In this report, the environmental
      sustainability of reusable and disposable cleanroom coveralls is examined using a
      technique called life cycle assessment. With this technique, environmental
      parameters such as energy use and greenhouse gas emissions are quantified and
      compared for three market representative cleanroom coveralls, from raw material
      extraction through manufacturing, use, and final disposal. Reusable coveralls
      were found to substantially outperform disposable coveralls in all environmental
      parameters examined. This is an important conclusion that supports cleanroom
      companies that select reusable coveralls to be more sustainable.

PMID- 29444995
TI  - PDA Points to Consider: Best Practices for Document/Data Management and Control
      and Preparing for Data Integrity Inspections.
AB  - The Parenteral Drug Association (PDA) has identified 11 current questions related
      to data management and control that have been frequently cited in U.S. Food and
      Drug Administration (FDA) inspections or have led to FDA regulatory actions. The
      purpose of this document is to help to clarify some of these issues for industry
      and to help facilitate better compliance by sharing PDA members' expertise in and
      understanding of current best practices.Data integrity inspectional observations
      by health authorities can have a severe impact on a firm from a regulatory and
      public perception perspective and should not result from a lack of clarity by
      industry about what is required. In addition, firms are concerned that the
      inability to produce a requested record or document during an inspection, even if
      not a standard report or existing quality system document, could be construed as
      delaying, denying, limiting, or refusing inspection, which also has significant
      consequences.The PDA acknowledges it may not be possible for a single firm or
      site to have a meaningful discussion of these issues in the context of an
      inspection or inspection response and is offering these best practices so that
      industry can proactively comply and properly prioritize its efforts to improve
      document management and control and good manufacturing practices in the most
      efficient and effective means possible. The PDA acknowledges there are many more
      questions to be addressed and hopes that there can be an ongoing dialogue between
      industry and regulators to facilitate answers.

PMID- 29444996
TI  - A Model of Risk Analysis in Analytical Methodology for Biopharmaceutical Quality
      Control.
AB  - One key quality control parameter for biopharmaceutical products is the analysis
      of residual cellular DNA. To determine small amounts of DNA (around 100 pg) that
      may be in a biologically derived drug substance, an analytical method should be
      sensitive, robust, reliable, and accurate. In principle, three techniques have
      the ability to measure residual cellular DNA: radioactive dot-blot, a type of
      hybridization; threshold analysis; and quantitative polymerase chain reaction.
      Quality risk management is a systematic process for evaluating, controlling, and
      reporting of risks that may affects method capabilities and supports a scientific
      and practical approach to decision making. This paper evaluates, by quality risk
      management, an alternative approach to assessing the performance risks associated
      with quality control methods used with biopharmaceuticals, using the tool hazard
      analysis and critical control points. This tool provides the possibility to find
      the steps in an analytical procedure with higher impact on method performance. By
      applying these principles to DNA analysis methods, we conclude that the
      radioactive dot-blot assay has the largest number of critical control points,
      followed by quantitative polymerase chain reaction, and threshold analysis. From
      the analysis of hazards (i.e., points of method failure) and the associated
      method procedure critical control points, we conclude that the analytical
      methodology with the lowest risk for performance failure for residual cellular
      DNA testing is quantitative polymerase chain reaction.LAY ABSTRACT: In order to
      mitigate the risk of adverse events by residual cellular DNA that is not
      completely cleared from downstream production processes, regulatory agencies have
      required the industry to guarantee a very low level of DNA in biologically
      derived pharmaceutical products. The technique historically used was radioactive
      blot hybridization. However, the technique is a challenging method to implement
      in a quality control laboratory: It is laborious, time consuming, semi
      quantitative, and requires a radioisotope. Along with dot-blot hybridization, two
      alternatives techniques were evaluated: threshold analysis and quantitative
      polymerase chain reaction. Quality risk management tools were applied to compare
      the techniques, taking into account the uncertainties, the possibility of
      circumstances or future events, and their effects upon method performance. By
      illustrating the application of these tools with DNA methods, we provide an
      example of how they can be used to support a scientific and practical approach to
      decision making and can assess and manage method performance risk using such
      tools. This paper discusses, considering the principles of quality risk
      management, an additional approach to the development and selection of analytical
      quality control methods using the risk analysis tool hazard analysis and critical
      control points. This tool provides the possibility to find the method procedural
      steps with higher impact on method reliability (called critical control points).
      Our model concluded that the radioactive dot-blot assay has the larger number of
      critical control points, followed by quantitative polymerase chain reaction and
      threshold analysis. Quantitative polymerase chain reaction is shown to be the
      better alternative analytical methodology in residual cellular DNA analysis.

PMID- 29444997
TI  - Efficacy of multicomponent culturally tailored HIV/ STI prevention interventions
      targeting foreign female entertainment workers: a quasi-experimental trial.
AB  - OBJECTIVES: We assessed the efficacy of a multicomponent culturally tailored
      HIV/STI prevention intervention programme on consistent condom use and STI
      incidence among foreign Thai and Vietnamese female entertainment workers (FEWs)
      in Singapore. METHODS: We conducted a quasi-experimental pretest and post-test
      intervention trial with a comparison group. We recruited 220 participants (115
      Vietnamese and 105 Thai) for the comparison group, followed by the intervention
      group (same number) from the same sites which were purposively selected after a 3
      month interval period. Both groups completed a self-administered anonymous
      questionnaire and STI testing for cervical gonorrhoea and Chlamydia, as well as
      pharyngeal gonorrhoea at baseline and 6-week follow-up. The peer-led intervention
      consisted of behavioural (HIV/STI education and condom negotiation skills),
      biomedical (STI screening and treatment services) and structural components
      (access to free condoms). We used the mixed effects Poisson regression model
      accounting for clustering by establishment venue to compute the adjusted risk
      ratio (aRR) of the outcomes at follow-up. RESULTS: At follow-up, the intervention
      group was more likely than the comparison group to report consistent condom use
      for vaginal sex with paid (aRR 1.77; 95% CI 1.71 to 1.83) and casual (aRR 1.81;
      95% CI 1.71 to 1.91) partners. For consistent condom use for oral sex, this was
      aRR 1.50; 95% CI 1.23 to 1.82 with paid and aRR 1.54; 95% CI 1.22 to 1.95 with
      casual partners. STI incidence at follow-up was significantly lower in the
      intervention (6.8 per 100 FEWs) than the comparison (14.8 per 100 FEWs) group
      (aRR 0.42; 95% CI 0.32 to 0.55). CONCLUSIONS: This trial was effective in
      promoting consistent condom use for vaginal and oral sex as well as reducing STI
      incidence among the foreign Thai and Vietnamese FEWs in Singapore. The
      feasibility of scaling up the interventions to all entertainment establishments
      in Singapore should be assessed.

PMID- 29444999
TI  - Percutaneous Management of Aortic Root Rupture During Transcatheter Aortic Valve
      Replacement With Coil Embolization.

PMID- 29444998
TI  - Treatment of Aortic Stenosis With a Self-Expanding, Resheathable Transcatheter
      Valve: One-Year Results of the International Multicenter Portico Transcatheter
      Aortic Valve Implantation System Study.
AB  - BACKGROUND: The aim of the Portico TAVI (transcatheter aortic valve implantation)
      system study was to evaluate outcomes <=1 year after implantation of a novel
      resheathable, self-expanding TAVI system in a multicenter patient population with
      severe aortic stenosis (AS). METHODS AND RESULTS: High-risk patients (n=222) with
      symptomatic severe AS (mean age, 83.0+/-4.6 years; 74.3% women) were enrolled
      across 12 centers in Europe and Australia. The study's primary end point was all
      cause mortality at 30 days. A total of 209 patients who received the Portico TAVI
      system were available for follow-up after the 30-day visit. Data collection
      included hemodynamic assessment by echocardiography with core laboratory
      evaluation and assessment of functional status. Valve Academic Research
      Consortium-defined adverse events were adjudicated by an independent Clinical
      Events Committee. TAVI using the Portico valve led to a significant and
      persistent improvement in aortic valve function at 1 year. More than mild
      paravalvular leak was present in 5.7% and 7.5% of patients at 30 days and 1 year,
      respectively. Kaplan-Meier estimates at 30 days and 1 year were 3.6% and 13.8%
      for all-cause mortality, 3.6% and 9.6% for cardiovascular mortality, and 3.2% and
      5.8% for major (disabling) stroke. After 30 days and <=1 year of follow-up,
      adverse events included stage 3 acute kidney injury (n=3), major vascular
      complications (n=5), and life-threatening/disabling bleeding (n=3). Overall
      permanent pacemaker rate was 14.7%. At 1 year, 74.8% improved >=1 New York Heart
      Association class compared with baseline (P<0.0001). CONCLUSIONS: The Portico
      TAVI system is safe and effective at 1 year, yielding low mortality and stroke
      rates in high-risk patients with severe AS. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT01493284.

PMID- 29445000
TI  - Retroperitoneal Hemorrhage After Percutaneous Coronary Intervention: Incidence,
      Determinants, and Outcomes as Recorded by the British Cardiovascular Intervention
      Society.
AB  - BACKGROUND: Retroperitoneal hemorrhage (RH) is a rare bleeding complication of
      percutaneous coronary intervention, which can result as a consequence of femoral
      access or can occur spontaneously. This study aims to evaluate temporal changes
      in RH, its predictors, and clinical outcomes in a national cohort of patients
      undergoing percutaneous coronary intervention in the United Kingdom. METHODS AND
      RESULTS: We analyzed RH events in patients who underwent percutaneous coronary
      intervention between 2007 and 2014. Multiple logistic regression models were used
      to identify factors associated with RH and to quantify the association between RH
      and 30-day mortality and major adverse cardiovascular events. A total of 511 106
      participants were included, and 291 in hospital RH events were recorded (0.06%).
      Overall, rates of RH declined from 0.09% to 0.03% between 2007 and 2014. The
      strongest independent predictors of RH events were femoral access (odds ratio
      [OR], 19.66; 95% confidence interval [CI], 11.22-34.43), glycoprotein IIb/IIIa
      inhibitor (OR, 2.63; 95% CI, 1.99-3.47), and warfarin use (OR, 2.53; 95% CI, 1.07
      5.99). RH was associated with a significant increase in 30-day mortality (OR,
      3.59; 95% CI, 2.19-5.90) and in-hospital major adverse cardiovascular events (OR,
      5.76; 95% CI, 3.71-8.95). A legacy effect was not observed; patients with RH who
      survived 30 days did not have higher 1-year mortality compared with those without
      this complication (hazard ratio, 0.97; 95% CI, 0.49-1.91). CONCLUSIONS: Our
      results suggest that RH is a rare event that is declining in the United Kingdom,
      related to transition to transradial access site utilization, but remains a
      clinically important event associated with increased 30-day mortality but no long
      term legacy effect.

PMID- 29445001
TI  - Interventional Treatment of Severe Tricuspid Regurgitation: Early Clinical
      Experience in a Multicenter, Observational, First-in-Man Study.
AB  - BACKGROUND: Transcatheter caval valve implantation is under evaluation as a
      treatment option for inoperable patients with severe tricuspid regurgitation
      (TR). The procedure involves the catheter-based implantation of bioprosthetic
      valves in the inferior vena cava and superior vena cava to treat symptoms
      associated with TR. This study is the first to evaluate the feasibility, safety,
      and efficacy of this interventional concept. METHODS AND RESULTS: Twenty-five
      patients (mean age, 73.9+/-7.6 years; women, 52.0%) with severe symptomatic TR
      despite optimal medical treatment deemed unsuitable for surgery were treated with
      caval valve implantation under a compassionate clinical use program. Technical
      feasibility defined as procedural success, hemodynamic effect defined as venous
      pressure reduction, and safety defined as periprocedural adverse events were
      evaluated, with clinical follow-up at discharge and up to 12 months. The
      functional impact was evaluated by assessment of New York Heart Association class
      at the time of hospital discharge. The total number of valves implanted in the
      caval position was 31. Patients were treated with single (inferior vena cava
      only; n=19; 76.0%) or bicaval valve implantation (inferior vena cava+superior
      vena cava; n=6; 24.0%). Either balloon-expandable valves (Sapien XT/3: n=18;
      72.0%) or self-expandable valves (TricValve: n=6; 24.0%; Directflow: n=1; 4.0%)
      were used. Procedural success was achieved in 96% (n=24). Early and late valve
      migration requiring surgical intervention occurred in 1 patient each. Thirty-day
      and in-hospital mortality were 8% (2 of 25) and 16% (4 of 25). Causes of in
      hospital mortality included respiratory (n=1) or multiple organ failure (n=3) and
      were not linked to the procedure. Mean overall survival in the study cohort was
      316+/-453 days (14-1540 days). CONCLUSIONS: Caval valve implantation for the
      treatment of severe TR and advanced right ventricular failure is associated with
      a high procedural success rate and seems safe and feasible in an excessive-risk
      cohort. The study demonstrates hemodynamic efficacy with consistent elimination
      of TR-associated venous backflow and initial clinical improvement. These results
      encourage further trials to determine which patients benefit most from this
      interventional approach.

PMID- 29445002
TI  - Embolization of Neoatherosclerosis After Percutaneous Coronary Intervention:
      Insights From Near-Infrared Spectroscopy Imaging and Histopathological Analysis.

PMID- 29445004
TI  - Caval Valve Implantation: Are 2 Valves Better Than 1?

PMID- 29445003
TI  - Bleeding Edge Technology: Retroperitoneal Hemorrhage and Its Implications for
      Transradial Access.

PMID- 29445005
TI  - Portico at 1 Year: "There is Nothing Like First-Hand Evidence"-Sir Arthur Conan
      Doyle. A Study in Scarlet, 1887.

PMID- 29445006
TI  - Inflammatory Monocytes Drive Influenza A Virus-Mediated Lung Injury in Juvenile
      Mice.
AB  - Healthy children are more likely to die of influenza A virus (IAV) infection than
      healthy adults. However, little is known about the mechanisms underlying the
      impact of young age on the development of life-threatening IAV infection. We
      report increased mortality in juvenile mice compared with adult mice at each
      infectious dose of IAV. Juvenile mice had sustained elevation of type I IFNs and
      persistent NLRP3 inflammasome activation in the lungs, both of which were
      independent of viral titer. Juvenile mice, but not adult mice, had increased MCP
      1 levels that remained high even after viral clearance. Importantly, continued
      production of MCP-1 was associated with persistent recruitment of monocytes to
      the lungs and prolonged elevation of inflammatory cytokines. Transcriptional
      signatures of recruited monocytes to the juvenile and adult IAV-infected lungs
      were assessed by RNA-seq. Genes associated with a proinflammatory signature were
      upregulated in the juvenile monocytes compared with adult monocytes. Depletion of
      monocytes with anti-CCR2 Ab decreased type I IFN secretion, NLRP3 inflammasome
      activation, and lung injury in juvenile mice. This suggests an exaggerated
      inflammatory response mediated by increased recruitment of monocytes to the lung,
      and not an inability to control viral replication, is responsible for severe IAV
      infection in juvenile mice. This study provides insight into severe IAV infection
      in juveniles and identifies key inflammatory monocytes that may be central to
      pediatric acute lung injury secondary to IAV.

PMID- 29445007
TI  - Highly Efficient and Versatile Plasmid-Based Gene Editing in Primary T Cells.
AB  - Adoptive cell transfer is an important approach for basic research and emerges as
      an effective treatment for various diseases, including infections and blood
      cancers. Direct genetic manipulation of primary immune cells opens up
      unprecedented research opportunities and could be applied to enhance cellular
      therapeutic products. In this article, we report highly efficient genome
      engineering in primary murine T cells using a plasmid-based RNA-guided CRISPR
      system. We developed a straightforward approach to ablate genes in up to 90% of
      cells and to introduce precisely targeted single nucleotide polymorphisms in up
      to 25% of the transfected primary T cells. We used gene editing-mediated allele
      switching to quantify homology-directed repair, systematically optimize
      experimental parameters, and map a native B cell epitope in primary T cells.
      Allele switching of a surrogate cell surface marker can be used to enrich cells,
      with successful simultaneous editing of a second gene of interest. Finally, we
      applied the approach to correct two disease-causing mutations in the Foxp3 gene.
      Repairing the cause of the scurfy syndrome, a 2-bp insertion in Foxp3, and
      repairing the clinically relevant Foxp3K276X mutation restored Foxp3 expression
      in primary T cells.

PMID- 29445008
TI  - Blockade of Host beta2-Adrenergic Receptor Enhances Graft-versus-Tumor Effect
      through Modulating APCs.
AB  - Allogeneic hematopoietic cell transplantation is a potential curative therapy for
      hematologic malignancies. Host APCs are pivotal to the desired graft-versus-tumor
      (GVT) effect. Recent studies have shown that beta2-adrenergic receptor (beta2AR)
      signaling can have an important impact on immune cell function, including
      dendritic cells (DCs). In this article, we demonstrate that pretreatment of host
      mice with a beta2AR blocker significantly increases the GVT effect of donor CD8+
      T cells by decreasing tumor burden without increasing graft-versus-host disease.
      beta2AR-deficient host mice have significantly increased effector memory and
      central memory CD8+ T cells and improved reconstitution of T cells, including
      CD4+Foxp3+ regulatory T cells. Notably, beta2AR deficiency induces increased
      CD11c+ DC development. Also, beta2AR-deficient bone marrow-derived DCs induce
      higher CD8+ T cell proliferation and improved tumor killing in vitro. Metabolic
      profiling shows that beta2AR deficiency renders DCs more immunogenic through
      upregulation of mTOR activity and reduction of STAT3 phosphorylation. Altogether,
      these findings demonstrate an important role for host beta2AR signaling in
      suppressing T cell reconstitution and GVT activity.

PMID- 29445009
TI  - Human Binge Alcohol Intake Inhibits TLR4-MyD88 and TLR4-TRIF Responses but Not
      the TLR3-TRIF Pathway: HspA1A and PP1 Play Selective Regulatory Roles.
AB  - Binge/moderate alcohol suppresses TLR4-MyD88 proinflammatory cytokines; however,
      alcohol's effects on TLR-TRIF signaling, especially after in vivo exposure in
      humans, are unclear. We performed a comparative analysis of the TLR4-MyD88, TLR4
      TRIF, and TLR3-TRIF pathways in human monocytes following binge alcohol exposure.
      Mechanistic regulation of TLR-TRIF signaling by binge alcohol was evaluated by
      analyzing IRF3 and TBK1, upstream regulator protein phosphatase 1 (PP1), and
      immunoregulatory stress proteins HspA1A and XBP-1 in alcohol-treated human and
      mouse monocytes/macrophages. Two approaches for alcohol exposure were used: in
      vivo exposure of primary monocytes in binge alcohol-consuming human volunteers or
      in vitro exposure of human monocytes/murine macrophages to physiological alcohol
      concentrations (25-50 mM ethanol), followed by LPS (TLR4) or polyinosinic
      polycytidylic acid (TLR3) stimulation ex vivo. In vivo and in vitro binge alcohol
      exposure significantly inhibited the TLR4-MyD88 cytokines TNF-alpha and IL-6, as
      well as the TLR4-TRIF cytokines/chemokines IFN-beta, IP-10, and RANTES, in human
      monocytes, but not TLR3-TRIF-induced cytokines/chemokines, as detected by
      quantitative PCR and ELISA. Mechanistic analyses revealed TBK-1-independent
      inhibition of the TLR4-TRIF effector IRF3 in alcohol-treated macrophages.
      Although stress protein XBP-1, which is known to regulate IRF3-mediated IFN-beta
      induction, was not affected by alcohol, HspA1A was induced by in vivo alcohol in
      human monocytes. Alcohol-induced HspA1A was required for inhibition of TLR4-MyD88
      signaling but not TLR4-TRIF cytokines in macrophages. In contrast, inhibition of
      PP1 prevented alcohol-mediated TLR4-TRIF tolerance in macrophages. Collectively,
      our results demonstrate that in vivo and in vitro binge alcohol exposure in
      humans suppresses TLR4-MyD88 and TLR4-TRIF, but not TLR3-TRIF, responses. Whereas
      alcohol-mediated effects on the PP1-IRF3 axis inhibit the TLR4-TRIF pathway,
      HspA1A selectively suppresses the TLR4-MyD88 pathway in monocytes/macrophages.

PMID- 29445010
TI  - Ethical dilemmas encountered by small animal veterinarians: characterisation,
      responses, consequences and beliefs regarding euthanasia.
AB  - Small animal veterinarians' opinions were investigated regarding the frequency
      and nature of ethical dilemmas encountered, beliefs regarding euthanasia and
      balancing client and animal interests, prevalence and value of ethics training
      and proposals to mitigate the stressful effects of ethical dilemmas. The majority
      (52 per cent) of 484 respondents in the USA indicated via an online survey
      experiencing an ethical dilemma regarding the interests of clients and those of
      their patients at least weekly. Scenarios involving client financial concerns
      were commonly reported causes of ethical conflicts. While only 20 per cent of
      respondents indicated that other practitioners prioritise patient interests, 50
      per cent of respondents characterised their own behaviour as prioritising
      patients. Most respondents (52 per cent) reported that ethical dilemmas are the
      leading cause, or are one of many equal causes, of work-related stress. Less
      experienced practitioners, general practitioners and associate veterinarians were
      more likely to encounter situations they defined as ethical dilemmas, and female
      respondents were more likely to find ethical dilemmas stressful. Most small
      animal veterinarians experience ethical dilemmas regularly, which contribute to
      moral stress. Results suggested that most small animal practitioners believe that
      greater awareness of moral stress and providing training in ethical theories and
      tools for coping with ethical dilemmas can ameliorate moral stress.

PMID- 29445011
TI  - Understanding veterinary leadership in practice.
AB  - The Vet Futures Report has identified 'exceptional leadership' as a key ambition
      for the long-term sustainability of the industry. This research investigates what
      it is like to be a veterinary surgeon in an in-practice leadership position,
      applying the qualitative methodology of interpretative phenomenological analysis.
      Through the researchers' interpretation of the seven participants' stories of
      their leadership experiences, the study advances understanding of the work
      environment, underlying motivations and the perceived responsibilities of
      veterinary leaders. Findings suggest, for many, a struggle in transition to
      leader positions, improving with time. The increase in pace of work is relayed by
      participants, with an ongoing, and unchallenged, work-life imbalance. The vets
      involved are highly motivated, driven by enjoyment of their jobs, a desire for
      self-determination and a need to make a difference. Relationships form the core
      of the perceived responsibilities, and yet are identified as the greatest day-to
      day challenge of leadership. This study offers a valuable insight for veterinary
      surgeons, suggesting the industry could benefit from pausing and reflecting on
      behaviours. With a greater understanding of the complexity of leadership and
      followership, progress can be made to enact positive changes for the future.

PMID- 29445012
TI  - Counterintuitive increase in observed Mycobacterium avium subspecies
      paratuberculosis prevalence in sympatric rabbits following the introduction of
      paratuberculosis control measures in cattle.
AB  - Paratuberculosis (Johne's disease) is caused by the bacterium Mycobacterium avium
      subspecies paratuberculosis (Map). Achieving herd-level control of mycobacterial
      infection is notoriously difficult, despite widespread adoption of test-and-cull
      based control strategies. The presence of infection in wildlife populations could
      be contributing to this difficulty. Rabbits are naturally infected with the same
      Map strain as cattle, and can excrete high levels in their faeces. The aim of
      this study is to determine if implementation of paratuberculosis control in
      cattle leads to a decline in Map infection levels in rabbits. An island-wide,
      test-and-cull-based paratuberculosis control programme was initiated on a
      Scottish island in 2008. In this study annual tests were obtained from 15 cattle
      farms, from 2008 to 2011, totalling 2609 tests. Rabbits (1564) were sampled from
      the 15 participating farms, from 2008 to 2011, and Map was detected by faecal
      culture. Map seroprevalence in cattle decreased from 16 to 7.2 per cent, while
      Map prevalence in rabbits increased from 10.3 to 20.3 per cent. Results indicate
      that efforts to control paratuberculosis in cattle do not reduce Map levels in
      sympatric rabbits. This adds to mounting evidence that if Map becomes established
      in wild rabbit populations, rabbits represent a persistent and widespread source
      of infection, potentially impeding livestock control strategies.

PMID- 29445013
TI  - Spatial and temporal patterns of Schmallenberg virus in France in 2016.

PMID- 29445014
TI  - Effect of on-farm interventions in the aftermath of an outbreak of hypervirulent
      verocytotoxin-producing Escherichia coli O157:H7 in Sweden.
AB  - In 2007, human infections with a hypervirulent strain of verocytotoxin-producing
      Escherichia coli O157:H7 increased in Sweden and especially in the Halland
      County. A connection between the cases and a local beef cattle farm with an on
      farm abattoir and meat processing plant was established. In this observational
      study the control measures implemented on the infected farm and the dynamics of
      infection in the herd are described. In May 2008, when measures were initiated
      and animals put to pasture, the prevalence of positive individuals was 40 per
      cent and 18 carcasses out of 24 slaughtered animals were contaminated. During
      summer the monthly prevalence of positive carcasses varied between 8 and 41 per
      cent and at turning-in 22 out of 258 individually sampled animals were shedding
      the pathogen. After January 2009 no positive carcasses were found at slaughter
      and follow-up samplings of environment and individuals remained negative until
      the study period ended in May 2010. The results indicate that on-farm measures
      have potential to reduce the prevalence of the pathogen in a long-term
      perspective. However, as self-clearance cannot be excluded the effectiveness of
      the suggested measures needs to be confirmed.

PMID- 29445015
TI  - Influence of ageing on quantitative contrast-enhanced ultrasound of the kidneys
      in healthy cats.
AB  - The degenerative effects of ageing on the kidneys have been extensively studied
      in humans. However, only recently interest has been focused on renal ageing in
      veterinary medicine. Contrast-enhanced ultrasound allows non-invasive evaluation
      of renal perfusion in conscious cats. Renal perfusion parameters were obtained in
      43 healthy cats aged 1-16 years old, and the cats were divided in four age
      categories: 1-3 years, 3-6 years, 6-10 years and over 10 years. Routine renal
      parameters as serum creatinine, serum urea, urine-specific gravity, urinary
      protein:creatinine ratio and systolic blood pressure were also measured. No
      significant differences in any of the perfusion parameters were observed among
      the different age categories. A trend towards a lower peak enhancement and wash
      in area under the curve with increasing age, suggestive for a lower blood volume,
      was detected when comparing the cats over 10 years old with the cats of 1-3 years
      old. Additionally, no significant age-effect was observed for the serum and urine
      parameters, whereas a higher blood pressure was observed in healthy cats over 10
      years old.

PMID- 29445016
TI  - Antibodies to Coxiella burnetii in Irish bulk tank milk samples.

PMID- 29445018
TI  - High rates of vessel noise disrupt foraging in wild harbour porpoises (Phocoena
      phocoena).
AB  - Shipping is the dominant marine anthropogenic noise source in the world's oceans,
      yet we know little about vessel encounter rates, exposure levels and behavioural
      reactions for cetaceans in the wild, many of which rely on sound for foraging,
      communication and social interactions. Here, we used animal-borne acoustic tags
      to measure vessel noise exposure and foraging efforts in seven harbour porpoises
      in highly trafficked coastal waters. Tagged porpoises encountered vessel noise 17
      89% of the time and occasional high-noise levels coincided with vigorous fluking,
      bottom diving, interrupted foraging and even cessation of echolocation, leading
      to significantly fewer prey capture attempts at received levels greater than 96
      dB re 1 uPa (16 kHz third-octave). If such exposures occur frequently, porpoises,
      which have high metabolic requirements, may be unable to compensate energetically
      with negative long-term fitness consequences. That shipping noise disrupts
      foraging in the high-frequency-hearing porpoise raises concerns that other
      toothed whale species may also be affected.

PMID- 29445017
TI  - Landscape configurational heterogeneity by small-scale agriculture, not crop
      diversity, maintains pollinators and plant reproduction in western Europe.
AB  - Agricultural intensification is one of the main causes for the current
      biodiversity crisis. While reversing habitat loss on agricultural land is
      challenging, increasing the farmland configurational heterogeneity (higher field
      border density) and farmland compositional heterogeneity (higher crop diversity)
      has been proposed to counteract some habitat loss. Here, we tested whether
      increased farmland configurational and compositional heterogeneity promote wild
      pollinators and plant reproduction in 229 landscapes located in four major
      western European agricultural regions. High-field border density consistently
      increased wild bee abundance and seed set of radish (Raphanus sativus), probably
      through enhanced connectivity. In particular, we demonstrate the importance of
      crop-crop borders for pollinator movement as an additional experiment showed
      higher transfer of a pollen analogue along crop-crop borders than across fields
      or along semi-natural crop borders. By contrast, high crop diversity reduced bee
      abundance, probably due to an increase of crop types with particularly intensive
      management. This highlights the importance of crop identity when higher crop
      diversity is promoted. Our results show that small-scale agricultural systems can
      boost pollinators and plant reproduction. Agri-environmental policies should
      therefore aim to halt and reverse the current trend of increasing field sizes and
      to reduce the amount of crop types with particularly intensive management.

PMID- 29445019
TI  - Wound treatment and selective help in a termite-hunting ant.
AB  - Open wounds are a major health risk in animals, with species prone to injuries
      likely developing means to reduce these risks. We therefore analysed the
      behavioural response towards open wounds on the social and individual level in
      the termite group-hunting ant Megaponera analis During termite raids, some ants
      get injured by termite soldiers (biting off extremities), after the fight injured
      ants get carried back to the nest by nest-mates. We observed treatment of the
      injury by nest-mates inside the nest through intense allogrooming at the wound.
      Lack of treatment increased mortality from 10% to 80% within 24 h, most likely
      due to infections. Wound clotting occurred extraordinarily fast in untreated
      injured individuals, within 10 min. Furthermore, heavily injured ants (loss of
      five extremities) were not rescued or treated; this was regulated not by the
      helper but by the unresponsiveness of the injured ant. Interestingly, lightly
      injured ants behaved 'more injured' near nest-mates. We show organized social
      wound treatment in insects through a multifaceted help system focused on injured
      individuals. This was not only limited to selective rescuing of lightly injured
      individuals by carrying them back (thus reducing predation risk), but, moreover,
      included a differentiated treatment inside the nest.

PMID- 29445020
TI  - Trade-offs between microbial growth phases lead to frequency-dependent and non
      transitive selection.
AB  - Mutations in a microbial population can increase the frequency of a genotype not
      only by increasing its exponential growth rate, but also by decreasing its lag
      time or adjusting the yield (resource efficiency). The contribution of multiple
      life-history traits to selection is a critical question for evolutionary biology
      as we seek to predict the evolutionary fates of mutations. Here we use a model of
      microbial growth to show that there are two distinct components of selection
      corresponding to the growth and lag phases, while the yield modulates their
      relative importance. The model predicts rich population dynamics when there are
      trade-offs between phases: multiple strains can coexist or exhibit bistability
      due to frequency-dependent selection, and strains can engage in rock-paper
      scissors interactions due to non-transitive selection. We characterize the
      environmental conditions and patterns of traits necessary to realize these
      phenomena, which we show to be readily accessible to experiments. Our results
      provide a theoretical framework for analysing high-throughput measurements of
      microbial growth traits, especially interpreting the pleiotropy and correlations
      between traits across mutants. This work also highlights the need for more
      comprehensive measurements of selection in simple microbial systems, where the
      concept of an ordinary fitness landscape breaks down.

PMID- 29445021
TI  - The influence of the few: a stable 'oligarchy' controls information flow in house
      hunting ants.
AB  - Animals that live together in groups often face difficult choices, such as which
      food resource to exploit, or which direction to flee in response to a predator.
      When there are costs associated with deadlock or group fragmentation, it is
      essential that the group achieves a consensus decision. Here, we study consensus
      formation in emigrating ant colonies faced with a binary choice between two
      identical nest-sites. By individually tagging each ant with a unique radio
      frequency identification microchip, and then recording all ant-to-ant 'tandem
      runs'-stereotyped physical interactions that communicate information about
      potential nest-sites-we assembled the networks that trace the spread of consensus
      throughout the colony. Through repeated emigrations, we show that both the order
      in which these networks are assembled and the position of each individual within
      them are consistent from emigration to emigration. We demonstrate that the
      formation of the consensus is delegated to an influential but exclusive minority
      of highly active individuals-an 'oligarchy'-which is further divided into two
      subgroups, each specialized upon a different tandem running role. Finally, we
      show that communication primarily occurs between subgroups not within them, and
      further, that such between-group communication is more efficient than within
      group communication.

PMID- 29445022
TI  - Whole genome duplication and transposable element proliferation drive genome
      expansion in Corydoradinae catfishes.
AB  - Genome size varies significantly across eukaryotic taxa and the largest changes
      are typically driven by macro-mutations such as whole genome duplications (WGDs)
      and proliferation of repetitive elements. These two processes may affect the
      evolutionary potential of lineages by increasing genetic variation and changing
      gene expression. Here, we elucidate the evolutionary history and mechanisms
      underpinning genome size variation in a species-rich group of Neotropical
      catfishes (Corydoradinae) with extreme variation in genome size-0.6 to 4.4 pg per
      haploid cell. First, genome size was quantified in 65 species and mapped onto a
      novel fossil-calibrated phylogeny. Two evolutionary shifts in genome size were
      identified across the tree-the first between 43 and 49 Ma (95% highest posterior
      density (HPD) 36.2-68.1 Ma) and the second at approximately 19 Ma (95% HPD 15.3
      30.14 Ma). Second, restriction-site-associated DNA (RAD) sequencing was used to
      identify potential WGD events and quantify transposable element (TE) abundance in
      different lineages. Evidence of two lineage-scale WGDs was identified across the
      phylogeny, the first event occurring between 54 and 66 Ma (95% HPD 42.56-99.5 Ma)
      and the second at 20-30 Ma (95% HPD 15.3-45 Ma) based on haplotype numbers per
      contig and between 35 and 44 Ma (95% HPD 30.29-64.51 Ma) and 20-30 Ma (95% HPD
      15.3-45 Ma) based on SNP read ratios. TE abundance increased considerably in
      parallel with genome size, with a single TE-family (TC1-IS630-Pogo) showing
      several increases across the Corydoradinae, with the most recent at 20-30 Ma (95%
      HPD 15.3-45 Ma) and an older event at 35-44 Ma (95% HPD 30.29-64.51 Ma). We
      identified signals congruent with two WGD duplication events, as well as an
      increase in TE abundance across different lineages, making the Corydoradinae an
      excellent model system to study the effects of WGD and TEs on genome and
      organismal evolution.

PMID- 29445023
TI  - Ocean acidification but not warming alters sex determination in the Sydney rock
      oyster, Saccostrea glomerata.
AB  - Whether sex determination of marine organisms can be altered by ocean
      acidification and warming during this century remains a significant, unanswered
      question. Here, we show that exposure of the protandric hermaphrodite oyster,
      Saccostrea glomerata to ocean acidification, but not warming, alters sex
      determination resulting in changes in sex ratios. After just one reproductive
      cycle there were 16% more females than males. The rate of gametogenesis, gonad
      area, fecundity, shell length, extracellular pH and survival decreased in
      response to ocean acidification. Warming as a sole stressor slightly increased
      the rate of gametogenesis, gonad area and fecundity, but this increase was masked
      by the impact of ocean acidification at a level predicted for this century.
      Alterations to sex determination, sex ratios and reproductive capacity will have
      flow on effects to reduce larval supply and population size of oysters and
      potentially other marine organisms.

PMID- 29445024
TI  - Quantitative analysis of the complete larval settlement process confirms Crisp's
      model of surface selectivity by barnacles.
AB  - For barnacle cypris larvae at the point of settlement, selection of an
      appropriate surface is critical. Since post-settlement relocation is usually
      impossible, barnacles have evolved finely tuned surface-sensing capabilities to
      identify suitable substrata, and a temporary adhesion system for extensive
      surface exploration. The pattern of exploratory behaviour appears complex and may
      last for several hours, imposing significant barriers to quantitative
      measurement. Here, we employ a novel tracking system that enables simultaneous
      analysis of the larval body movement of multiple individuals over their entire
      planktonic phase. For the first time, to our knowledge, we describe
      quantitatively the complete settlement process of cyprids as they explore and
      select surfaces for attachment. We confirm the 'classic' behaviours of wide
      searching, close searching and inspection that comprise a model originally
      proposed by Prof. Dennis Crisp FRS. Moreover, a short-term assay of cyprid body
      movement has identified inspection behaviour as the best indicator of propensity
      to settle, with more inspection-related movements occurring in conditions that
      also promote higher settlement. More than half a century after the model was
      first proposed by Crisp, there exists a precise method for quantifying cyprid
      settlement behaviour in wide-ranging investigations of barnacle ecology and
      applied studies of fouling management.

PMID- 29445026
TI  - Panobinostat and Multiple Myeloma in 2018.

PMID- 29445025
TI  - Strong conservation of inbred mouse strain microRNA loci but broad variation in
      brain microRNAs due to RNA editing and isomiR expression.
AB  - Diversity in the structure and expression of microRNAs, important regulators of
      gene expression, arises from SNPs, duplications followed by divergence,
      production of isomiRs, and RNA editing. Inbred mouse strains and crosses using
      them are important reference populations for genetic mapping, and as models of
      human disease. We determined the nature and extent of interstrain miRNA variation
      by (i) identifying miRNA SNPs in whole-genome sequence data from 36 strains, and
      (ii) examining miRNA editing and expression in hippocampus (Hpc) and frontal
      cortex (FCx) of six strains, to facilitate the study of miRNAs in neurobehavioral
      phenotypes. miRNA loci were strongly conserved among the 36 strains, but even the
      highly conserved seed region contained 16 SNPs. In contrast, we identified RNA
      editing in 58.9% of miRNAs, including 11 consistent editing events in the seed
      region. We confirmed the functional significance of three conserved edits in the
      miR-379/410 cluster, demonstrating that edited miRNAs gained novel target mRNAs
      not recognized by the unedited miRNAs. We found significant interstrain
      differences in miRNA and isomiR expression: Of 779 miRNAs expressed in Hpc and
      719 in FCx, 262 were differentially expressed (190 in Hpc, 126 in FCx, 54 in
      both). We also identified 32 novel miRNA candidates using miRNA prediction tools.
      Our studies provide the first comprehensive analysis of SNP, isomiR, and RNA
      editing variation in miRNA loci across inbred mouse strains, and a detailed
      catalog of expressed miRNAs in Hpc and FCx in six commonly used strains. These
      findings will facilitate the molecular analysis of neurological and behavioral
      phenotypes in this model organism.

PMID- 29445027
TI  - A Curative-Intent Trimodality Approach for Isolated Abdominal Nodal Metastases in
      Metastatic Colorectal Cancer: Update of a Single-Institutional Experience.
AB  - BACKGROUND: The purpose of this study was to define survival rates in patients
      with isolated advanced abdominal nodal metastases secondary to colorectal cancer
      (CRC), treated with curative-intent trimodality therapy. MATERIALS AND METHODS:
      Sixty-five patients received trimodality therapy, defined as chemotherapy
      delivered with external beam radiotherapy (EBRT) followed by lymphadenectomy and
      intraoperative radiotherapy (IORT). Infusional 5-fluorouracil was the most common
      radiosensitizer used (63%, 41 patients). The median dose of EBRT was 50 Gy, and
      the median dose of IORT was 12.5 Gy. We evaluated time to distant metastasis,
      toxicities, local failure within the EBRT field, recurrence within the IORT
      field, and survival. RESULTS: Fifty-two percent of patients were male; patients'
      median age was 50.5 years. All patients had an Eastern Cooperative Oncology Group
      score <=1. Twenty-nine patients had right-sided colon cancer, 22 had left-sided
      colon cancer, and 14 had rectal primaries. The median time from initial CRC
      diagnosis to development of abdominal nodal metastatic disease was 20.6 months
      (95% confidence interval [CI], 21.2-40.8 months). Seventy-eight percent (51
      patients) had para-aortic nodal metastases, 15% (10 patients) had mesenteric
      nodal metastases, and 6% (4 patients) had both. With a median follow-up of 77.6
      months, the median overall survival and 5-year estimated survival rate were 55.4
      months (95% CI, 47.2-80.9 months) and 45%, respectively. The median progression
      free survival was 19.3 months (95% CI, 16.5-32.8 months). Twenty-six (40%)
      patients never developed distant disease. The outcome was not affected by disease
      sidedness or rectal primary. Treatment was well tolerated without grade 3 or 4
      toxicities. CONCLUSION: Trimodality therapy produces sustainable long-term
      survival in selected patients with metastatic CRC presenting with isolated
      retroperitoneal or mesenteric nodal relapse. IMPLICATIONS FOR PRACTICE: This
      article reports a unique trimodality approach incorporating external beam
      radiotherapy with radiosensitizing chemotherapy, surgical resection, and
      intraoperative radiotherapy provides durable survival benefit with significant
      curative potential for patients with metastatic colorectal cancer who present
      with isolated abdominal nodal (mesenteric and/or retroperitoneal) recurrence.

PMID- 29445028
TI  - Evaluation of Treatment Patterns and Survival Outcomes in Elderly Pancreatic
      Cancer Patients: A Surveillance, Epidemiology, and End Results-Medicare Analysis.
AB  - BACKGROUND: Management of pancreatic cancer (PC) in elderly patients is unknown;
      clinical trials exclude patients with comorbidities and those of extreme age.
      This study evaluated treatment patterns and survival outcomes in elderly PC
      patients using linked Surveillance, Epidemiology, and End Results (SEER) and
      Medicare data. MATERIALS AND METHODS: Histology codes 8140, 8500, 8010, 8560,
      8490, 8000, 8260, 8255, 8261, 8263, 8020, 8050, 8141, 8144, 8210, 8211, or 8262
      in Medicare Parts A and B were identified. Data regarding demographic,
      characteristics, treatments, and vital status between 1998 and 2009 were
      collected from the SEER. Determinants of treatment receipt and overall survival
      were examined using logistic regression and Cox proportional hazards models,
      respectively. RESULTS: A total of 5,975 patients met inclusion. The majority of
      patients were non-Hispanic whites (85%) and female (55%). Most cases presented
      with locoregional stage disease (74%); 41% received only chemotherapy, 30%
      chemotherapy and surgery, 10% surgery alone, 3% radiation, and 16% no cancer
      directed therapy. Patients with more advanced cancer, older age, and those
      residing in areas of poverty were more likely to receive no treatment. Among
      patients 66-74 years of age with locoregional disease, surgery alone (hazard
      ratio [HR] = 0.54; 95% confidence interval [CI]: 0.39-0.74) and surgery in
      combination with chemotherapy (HR = 0.69; 95% CI: 0.53-0.91) showed survival
      benefit as compared with the no treatment group. Among patients >=75 years of age
      with locoregional disease, surgery alone (HR = 2.04; 95% CI: 0.87-4.8) or in
      combination with chemotherapy (HR = 1.59; 95% CI: 0.87-2.91) was not associated
      with better survival. CONCLUSION: Treatment modality and survival differs by age
      and stage. Low socioeconomic status appears to be a major barrier to the receipt
      of PC therapy among Medicare patients. IMPLICATIONS FOR PRACTICE: Elderly
      patients with cancer are under-represented on clinical trials and usually have
      comorbid illnesses. The management of elderly patients with pancreatic cancer is
      unknown, with many retrospective experiences but low sample sizes. Using
      Surveillance, Epidemiology, and End Results-Medicare linked data to analyze
      treatment patterns and survival of elderly patients with pancreatic cancer on a
      larger population scale, this study highlights treatment patterns and their
      effect on survival and proposes possible obstacles to access of care in elderly
      patients with pancreatic cancer other than Medicare coverage.

PMID- 29445029
TI  - Pantoprazole, an Inhibitor of the Organic Cation Transporter 2, Does Not
      Ameliorate Cisplatin-Related Ototoxicity or Nephrotoxicity in Children and
      Adolescents with Newly Diagnosed Osteosarcoma Treated with Methotrexate,
      Doxorubicin, and Cisplatin.
AB  - LESSONS LEARNED: Using a randomized crossover design and continuous variables
      such as change in hearing threshold and biomarkers of acute renal injury as short
      term endpoints, it was determined that pantoprazole, an organic cation
      transporter 2 inhibitor, did not ameliorate cisplatin-associated nephrotoxicity
      or ototoxicity.Cystatin C is a robust method to estimate glomerular filtration
      rate in patients with cancer. Using a patient-reported outcome survey, all
      patients identified tinnitus and subjective hearing loss occurring "at least
      rarely" after cycle 1, prior to objective high-frequency hearing loss measured by
      audiograms.New therapies that improve outcome with less acute and long-term
      toxicity are needed. BACKGROUND: Organic cation transporter 2 (OCT2), which is a
      cisplatin uptake transporter expressed on renal tubules and cochlear hair cells
      but not on osteosarcoma cells, mediates cisplatin uptake. Pantoprazole inhibits
      OCT2 and could ameliorate cisplatin ototoxicity and nephrotoxicity. Using a
      randomized crossover design, we evaluated audiograms, urinary acute kidney injury
      (AKI) biomarkers, and glomerular filtration rate (GFR) estimated from cystatin C
      (GFRcysC) in patients receiving cisplatin with and without pantoprazole.
      MATERIALS AND METHODS: Cisplatin (60 mg/m2 * 2 days per cycle) was administered
      concurrently with pantoprazole (intravenous [IV], 1.6 mg/kg over 4 hours) on
      cycles 1 and 2 or cycles 3 and 4 in 12 patients with osteosarcoma (OS) with a
      median (range) age of 12.8 (5.6-19) years. Audiograms, urinary AKI biomarkers,
      and serum cystatin C were monitored during each cycle. RESULTS: Pantoprazole had
      no impact on decrements in hearing threshold at 4-8 kHz, post-treatment elevation
      of urinary AKI biomarkers, or GFRcysC (Fig. 1, Table 1). Histological response
      (percent necrosis) after two cycles was similar with or without pantoprazole. All
      eight patients with localized OS at diagnosis are alive and in remission; three
      of four patients with metastases at diagnosis have died. CONCLUSION: Pantoprazole
      did not ameliorate cisplatin ototoxicity or nephrotoxicity. The decrease in
      GFRcysC and increase in N-acetyl-beta-glucosaminidase (NAG) and creatinine
      demonstrate that these biomarkers can quantify cisplatin glomerular and proximal
      tubular toxicity. OCT2 inhibition by pantoprazole did not appear to alter
      antitumor response or survival.

PMID- 29445030
TI  - Cabozantinib in Patients with Advanced Merkel Cell Carcinoma.
AB  - BACKGROUND: This study sought to determine the efficacy and safety profile of
      cabozantinib in patients with advanced Merkel cell carcinoma (MCC). EXPERIMENTAL
      DESIGN: This prospective, phase II, single-institution trial enrolled patients
      with platinum-failure, recurrent/metastatic MCC to receive cabozantinib 60 mg
      orally daily until disease progression, withdrawal from study, or severe
      toxicity. The primary endpoint was disease control rate. Secondary endpoints
      included overall survival (OS), progression-free survival (PFS), and toxicity.
      Immunohistochemistry for VEGFR-2, MET, and HGF expression and next-generation
      sequencing of tumor tissue were performed and correlated with outcome. RESULTS:
      Eight patients were accrued from January 24, 2014, to June 8, 2016. The study was
      closed prematurely because of toxicity and lack of responses. The most frequent
      adverse events were grades 1 and 2 and included anorexia, fatigue, nausea,
      hypothyroidism, and dysgeusia. Two patients developed nonhealing, painful ulcers
      and tumor-skin fistula. One patient had stable disease for 8 months. One patient
      withdrew from the study after 2 weeks of therapy because of adverse events. Three
      patients required dose reduction because of toxicity. Median PFS and OS were 2.1
      and 11.2 months, respectively. No expression of MET, HGF, or VEGFR-2 was
      identified in tumor cells by immunohistochemistry of patients' tissue samples.
      CONCLUSION: Cabozantinib was poorly tolerated and did not demonstrate activity in
      patients with recurrent/metastatic, platinum-failure MCC. It is unclear whether
      preselection of patients with the specific upregulation or genetic alteration in
      the targets for cabozantinib would have changed the results of this study.
      (Clinical trial identification number: NCT02036476) IMPLICATIONS FOR PRACTICE:
      This phase II study demonstrated poor tolerability and lack of activity of
      cabozantinib in an unselected group of patients with advanced Merkel cell
      carcinoma. Although it is unclear whether preselection of patients with the
      specific upregulation and genetic alterations in targets for cabozantinib would
      have changed the results of this study, this would have likely led to an
      extremely rare patient population that would take many years to accrue.

PMID- 29445031
TI  - The Perils of Single-Site Genetic Testing for Hereditary Cancer Syndromes in the
      Era of Next-Generation Sequencing.
AB  - : A challenge in counseling patients with a family history suggesting a
      hereditary cancer syndrome is deciding which genetic tests or panels to order. In
      this article, we discuss the identification of multiple familial mutations
      through genetic counseling and panel testing. For patients meeting National
      Comprehensive Cancer Network criteria for clinical genetic testing, providers
      should consider expanded panels to provide a more complete assessment of one's
      genetic risk. The continued use of expanded panel testing in the clinical setting
      will help inform optimal management of cancer patients, as well as the management
      of their unaffected family members. The mutation discovered in this case was in
      the ATM gene. The clinical significance of the mutation, potential therapeutic
      targets, and proper clinical management are discussed. KEY POINTS: With single
      site genetic testing, there is the potential to miss hereditary genetic syndromes
      that can be managed clinically.Between 4% and 6% of hereditary breast and ovarian
      cancer syndromes are caused by genes other than BRCA1 and BRCA2.ATM is a DNA
      mismatch repair gene associated with double-stranded DNA break repair and cell
      cycle checkpoint arrest.The risk of developing female breast cancer by age 50 and
      by age 80 in ATM heterozygotes is 9% and 17%-52%, respectively.

PMID- 29445032
TI  - MHF1-2/CENP-S-X performs distinct roles in centromere metabolism and genetic
      recombination.

PMID- 29445035
TI  - Comparative dynamics of microglial and glioma cell motility at the infiltrative
      margin of brain tumours.
AB  - Microglia are a major cellular component of gliomas, and abundant in the centre
      of the tumour and at the infiltrative margins. While glioma is a notoriously
      infiltrative disease, the dynamics of microglia and glioma migratory patterns
      have not been well characterized. To investigate the migratory behaviour of
      microglia and glioma cells at the infiltrative edge, we performed two-colour time
      lapse fluorescence microscopy of brain slices generated from a platelet-derived
      growth factor-B (PDGFB)-driven rat model of glioma, in which glioma cells and
      microglia were each labelled with one of two different fluorescent markers. We
      used mathematical techniques to analyse glioma cells and microglia motility with
      both single cell tracking and particle image velocimetry (PIV). Our results show
      microglia motility is strongly correlated with the presence of glioma, while the
      correlation of the speeds of glioma cells and microglia was variable and weak.
      Additionally, we showed that microglia and glioma cells exhibit different types
      of diffusive migratory behaviour. Microglia movement fit a simple random walk,
      while glioma cell movement fits a super diffusion pattern. These results show
      that glioma cells stimulate microglia motility at the infiltrative margins,
      creating a correlation between the spatial distribution of glioma cells and the
      pattern of microglia motility.

PMID- 29445034
TI  - The SKP1-Cullin-F-box E3 ligase betaTrCP and CDK2 cooperate to control STIL
      abundance and centriole number.
AB  - Deregulation of centriole duplication has been implicated in cancer and primary
      microcephaly. Accordingly, it is important to understand how key centriole
      duplication factors are regulated. E3 ubiquitin ligases have been implicated in
      controlling the levels of several duplication factors, including PLK4, STIL and
      SAS-6, but the precise mechanisms ensuring centriole homeostasis remain to be
      fully understood. Here, we have combined proteomics approaches with the use of
      MLN4924, a generic inhibitor of SCF E3 ubiquitin ligases, to monitor changes in
      the cellular abundance of centriole duplication factors. We identified human STIL
      as a novel substrate of SCF-betaTrCP. The binding of betaTrCP depends on a DSG
      motif within STIL, and serine 395 within this motif is phosphorylated in vivo SCF
      betaTrCP-mediated degradation of STIL occurs throughout interphase and mutations
      in the DSG motif causes massive centrosome amplification, attesting to the
      physiological importance of the pathway. We also uncover a connection between
      this new pathway and CDK2, whose role in centriole biogenesis remains poorly
      understood. We show that CDK2 activity protects STIL against SCF-betaTrCP
      mediated degradation, indicating that CDK2 and SCF-betaTrCP cooperate via STIL to
      control centriole biogenesis.

PMID- 29445036
TI  - Transition by head-on collision: mechanically mediated manoeuvres in cockroaches
      and small robots.
AB  - Exceptional performance is often considered to be elegant and free of 'errors' or
      missteps. During the most extreme escape behaviours, neural control can approach
      or exceed its operating limits in response time and bandwidth. Here we show that
      small, rapid running cockroaches with robust exoskeletons select head-on
      collisions with obstacles to maintain the fastest escape speeds possible to
      transition up a vertical wall. Instead of avoidance, animals use their passive
      body shape and compliance to negotiate challenging environments. Cockroaches
      running at over 1 m or 50 body lengths per second transition from the floor to a
      vertical wall within 75 ms by using their head like an automobile bumper,
      mechanically mediating the manoeuvre. Inspired by the animal's behaviour, we
      demonstrate a passive, high-speed, mechanically mediated vertical transitions
      with a small, palm-sized legged robot. By creating a collision model for animal
      and human materials, we suggest a size dependence favouring mechanical mediation
      below 1 kg that we term the 'Haldane limit'. Relying on the mechanical control
      offered by soft exoskeletons represents a paradigm shift for understanding the
      control of small animals and the next generation of running, climbing and flying
      robots where the use of the body can off-load the demand for rapid sensing and
      actuation.

PMID- 29445033
TI  - Rett syndrome: a neurological disorder with metabolic components.
AB  - Rett syndrome (RTT) is a neurological disorder caused by mutations in the X
      linked gene methyl-CpG-binding protein 2 (MECP2), a ubiquitously expressed
      transcriptional regulator. Despite remarkable scientific progress since its
      discovery, the mechanism by which MECP2 mutations cause RTT symptoms is largely
      unknown. Consequently, treatment options for patients are currently limited and
      centred on symptom relief. Thought to be an entirely neurological disorder, RTT
      research has focused on the role of MECP2 in the central nervous system. However,
      the variety of phenotypes identified in Mecp2 mutant mouse models and RTT
      patients implicate important roles for MeCP2 in peripheral systems. Here, we
      review the history of RTT, highlighting breakthroughs in the field that have led
      us to present day. We explore the current evidence supporting metabolic
      dysfunction as a component of RTT, presenting recent studies that have revealed
      perturbed lipid metabolism in the brain and peripheral tissues of mouse models
      and patients. Such findings may have an impact on the quality of life of RTT
      patients as both dietary and drug intervention can alter lipid metabolism.
      Ultimately, we conclude that a thorough knowledge of MeCP2's varied functional
      targets in the brain and body will be required to treat this complex syndrome.

PMID- 29445037
TI  - On the diverse roles of fluid dynamic drag in animal swimming and flying.
AB  - Questions of energy dissipation or friction appear immediately when addressing
      the problem of a body moving in a fluid. For the most simple problems, involving
      a constant steady propulsive force on the body, a straightforward relation can be
      established balancing this driving force with a skin friction or form drag,
      depending on the Reynolds number and body geometry. This elementary relation
      closes the full dynamical problem and sets, for instance, average cruising
      velocity or energy cost. In the case of finite-sized and time-deformable bodies
      though, such as flapping flyers or undulatory swimmers, the comprehension of
      driving/dissipation interactions is not straightforward. The intrinsic
      unsteadiness of the flapping and deforming animal bodies complicates the usual
      application of classical fluid dynamic forces balance. One of the complications
      is because the shape of the body is indeed changing in time, accelerating and
      decelerating perpetually, but also because the role of drag (more specifically
      the role of the local drag) has two different facets, contributing at the same
      time to global dissipation and to driving forces. This causes situations where a
      strong drag is not necessarily equivalent to inefficient systems. A lot of living
      systems are precisely using strong sources of drag to optimize their performance.
      In addition to revisiting classical results under the light of recent research on
      these questions, we discuss in this review the crucial role of drag from another
      point of view that concerns the fluid-structure interaction problem of animal
      locomotion. We consider, in particular, the dynamic subtleties brought by the
      quadratic drag that resists transverse motions of a flexible body or appendage
      performing complex kinematics, such as the phase dynamics of a flexible flapping
      wing, the propagative nature of the bending wave in undulatory swimmers, or the
      surprising relevance of drag-based resistive thrust in inertial swimmers.

PMID- 29445038
TI  - Quantitative modelling of nutrient-limited growth of bacterial colonies in
      microfluidic cultivation.
AB  - Nutrient gradients and limitations play a pivotal role in the life of all
      microbes, both in their natural habitat as well as in artificial, microfluidic
      systems. Spatial concentration gradients of nutrients in densely packed cell
      configurations may locally affect the bacterial growth leading to heterogeneous
      micropopulations. A detailed understanding and quantitative modelling of cellular
      behaviour under nutrient limitations is thus highly desirable. We use
      microfluidic cultivations to investigate growth and microbial behaviour of the
      model organism Corynebacterium glutamicum under well-controlled conditions. With
      a reaction-diffusion-type model, parameters are extracted from steady-state
      experiments with a one-dimensional nutrient gradient. Subsequently, we employ
      particle-based simulations with these parameters to predict the dynamical growth
      of a colony in two dimensions. Comparing the results of those simulations with
      microfluidic experiments yields excellent agreement. Our modelling approach lays
      the foundation for a better understanding of dynamic microbial growth processes,
      both in nature and in applied biotechnology.

PMID- 29445040
TI  - Tailoring drug release rates in hydrogel-based therapeutic delivery applications
      using graphene oxide.
AB  - Graphene oxide (GO) is increasingly used for controlling mass diffusion in
      hydrogel-based drug delivery applications. On the macro-scale, the density of GO
      in the hydrogel is a critical parameter for modulating drug release. Here, we
      investigate the diffusion of a peptide drug through a network of GO membranes and
      GO-embedded hydrogels, modelled as porous matrices resembling both laminated and
      'house of cards' structures. Our experiments use a therapeutic peptide and show a
      tunable nonlinear dependence of the peptide concentration upon time. We establish
      models using numerical simulations with a diffusion equation accounting for the
      photo-thermal degradation of fluorophores and an effective percolation model to
      simulate the experimental data. The modelling yields an interpretation of the
      control of drug diffusion through GO membranes, which is extended to the
      diffusion of the peptide in GO-embedded agarose hydrogels. Varying the density of
      micron-sized GO flakes allows for fine control of the drug diffusion. We further
      show that both GO density and size influence the drug release rate. The ability
      to tune the density of hydrogel-like GO membranes to control drug release rates
      has exciting implications to offer guidelines for tailoring drug release rates in
      hydrogel-based therapeutic delivery applications.

PMID- 29445039
TI  - Both lipopolysaccharide and lipoteichoic acids potently induce anomalous fibrin
      amyloid formation: assessment with novel AmytrackerTM stains.
AB  - In recent work, we discovered that the presence of highly substoichiometric
      amounts (10-8 molar ratio) of lipopolysaccharide (LPS) from Gram-negative
      bacteria caused fibrinogen clotting to lead to the formation of an amyloid form
      of fibrin. We here show that the broadly equivalent lipoteichoic acids (LTAs)
      from two species of Gram-positive bacteria have similarly (if not more) potent
      effects. Using thioflavin T fluorescence to detect amyloid as before, the
      addition of low concentrations of free ferric ion is found to have similar
      effects. Luminescent conjugated oligothiophene dyes (LCOs), marketed under the
      trade name AmytrackerTM, also stain classical amyloid structures. We here show
      that they too give very large fluorescence enhancements when clotting is
      initiated in the presence of the four amyloidogens (LPS, ferric ions and two LTA
      types). The staining patterns differ significantly as a function of both the
      amyloidogens and the dyes used to assess them, indicating clearly that the nature
      of the clots formed is different. This is also the case when clotting is measured
      viscometrically using thromboelastography. Overall, the data provide further
      evidence for an important role of bacterial cell wall products in the various
      coagulopathies that are observable in chronic, inflammatory diseases. The assays
      may have potential in both diagnostics and therapeutics.

PMID- 29445042
TI  - Working dogs transfer different tasks in reciprocal cooperation.
AB  - Direct reciprocity can establish stable cooperation among unrelated individuals.
      It is a common assumption of direct reciprocity models that agents exchange like
      with like, but this is not necessarily true for natural interactions. It is yet
      unclear whether animals apply direct reciprocity rules when successive altruistic
      help involves different tasks. Here, we tested whether working dogs transfer help
      from one to another cooperative task in an iterated prisoner's dilemma paradigm.
      In our experiment, individual dogs received help to obtain food from a
      conspecific, which involved a specific task. Subsequently, the focal subject
      could return received favour by using a different task. Working dogs transferred
      the cooperative experience received through one task by applying an alternative
      task when they helped a previously cooperative partner. By contrast, they
      refrained from helping previously defecting partners. This suggests that dogs
      realize the cooperative act of a conspecific, which changes their propensity to
      provide help to that partner by different means. The ability of animals to
      transfer different tasks when helping a social partner by satisfying the criteria
      of direct reciprocity might explain the frequent occurrence of reciprocal
      cooperation in nature.

PMID- 29445041
TI  - Generational shift in spring staging site use by a long-distance migratory bird.
AB  - In response to environmental change, species have been observed altering their
      migratory behaviours. Few studies, however, have been able to determine whether
      these alterations resulted from inherited, plastic or flexible changes. Here, we
      present a unique observation of a rapid population-level shift in migratory
      routes-over 300 km from Spain to Portugal-by continental black-tailed godwits
      Limosa limosa limosa This shift did not result from adult godwits changing
      staging sites, as adult site use was highly consistent. Rather, the shift
      resulted from young godwits predominantly using Portugal over Spain. We found no
      differences in reproductive success or survival among individuals using either
      staging site, indicating that the shift resulted from developmental plasticity
      rather than natural selection. Our results therefore suggest that new migratory
      routes can develop within a generation and that young individuals may be the
      agents of such rapid changes.

PMID- 29445043
TI  - Vestigial singing behaviour persists after the evolutionary loss of song in
      crickets.
AB  - The evolutionary loss of sexual traits is widely predicted. Because sexual
      signals can arise from the coupling of specialized motor activity with
      morphological structures, disruption to a single component could lead to overall
      loss of function. Opportunities to observe this process and characterize any
      remaining signal components are rare, but could provide insight into the
      mechanisms, indirect costs and evolutionary consequences of signal loss. We
      investigated the recent evolutionary loss of a long-range acoustic sexual signal
      in the Hawaiian field cricket Teleogryllus oceanicus Flatwing males carry
      mutations that remove sound-producing wing structures, eliminating all acoustic
      signalling and affording protection against an acoustically-orientating
      parasitoid fly. We show that flatwing males produce wing movement patterns
      indistinguishable from those that generate sonorous calling song in normal-wing
      males. Evolutionary song loss caused by the disappearance of structural
      components of the sound-producing apparatus has left behind the energetically
      costly motor behaviour underlying normal singing. These results provide a rare
      example of a vestigial behaviour and raise the possibility that such traits could
      be co-opted for novel functions.

PMID- 29445044
TI  - The extra burden of motherhood: reduced dive duration associated with pregnancy
      status in a deep-diving mammal, the northern elephant seal.
AB  - The cost of pregnancy is hard to study in marine mammals, particularly in species
      that undergo pregnancy while diving continuously at sea such as elephant seals
      (genus Mirounga). We analysed the diving behaviour of confirmed pregnant and non
      pregnant northern elephant seals (M. angustirostris, n = 172) and showed that
      after an initial continuous increase in dive duration, dives of pregnant females
      become shorter after week 17. The reasons for this reduction in dive duration
      remain unknown, but we hypothesize that increased fetal demand for oxygen could
      be the cause. Our findings reveal an opportunity to explore the use of biologging
      data to investigate pregnancy status of free-ranging marine mammals and factors
      that could affect pregnancy success.

PMID- 29445046
TI  - Expression of concern: Lionfish predators use flared fin displays to initiate
      cooperative hunting.

PMID- 29445045
TI  - Genomes to space stations: the need for the integrative study of migration for
      avian conservation.
AB  - Ongoing changes to global weather patterns and human modifications of the
      environment have altered the breeding and non-breeding ranges of migratory
      species, the timing of their migrations, and even whether they continue to
      migrate at all. Animal movements are arguably one of the most difficult
      behaviours to study, particularly in smaller birds that migrate tens to thousands
      of kilometres seasonally, often moving hundreds of kilometres each day. The
      recent miniaturization of tracking and logging devices has led to a radical
      transformation in our understanding of avian migratory behaviour and migratory
      connectivity. While advances in technology have altered the way researchers study
      migratory behaviour in the field, advances in techniques related to the study of
      physiological and genetic mechanisms underlying migratory behaviour have rarely
      been integrated into field studies of tracking. To predict the capacity of
      migrants to adjust to a changing planet, it is essential that we combine avian
      migration data with physiological and genetic measurements taken at key time
      points prior to, during and after migration.

PMID- 29445047
TI  - Association of Smoking with General and Abdominal Obesity: Evidence from a Cohort
      Study in West of Iran.
AB  - BACKGROUND: This study aimed to examine the association between smoking and
      obesity among adults in Kermanshah Province, west of Iran. STUDY DESIGN: A cross
      sectional study. METHODS: A total of 8822 participants, aged 35-65 yr, form
      Ravansar Non-communicable Disease (RaNCD) cohort study (2014-2016) were enrolled.
      Smoking habits were categorized in terms of smoking status (current, former and
      never smokers) and smoking intensity (light, moderate and heavy). General obesity
      was defined as body mass index (BMI) >=30 kg/m2 and abdominal obesity were
      defined as a waist to hip ratio (WHR) >=90 for men and >=85 for women. Multiple
      logistic regressions were used to examine the association between general and
      abdominal obesity with smoking status and smoking intensity while controlling for
      age, sex, years of education and wealth index. RESULTS: Overall, 12% were current
      smokers, 8.4% former smokers and 79.6% never smokers. The prevalence of light,
      moderate and heavy smokers among current smokers was 30.8%, 18%, and 51.2%,
      respectively. The prevalence of general obesity was 27.6%, while the prevalence
      of abdominal obesity was 82.3%. The probabilities of general and abdominal
      obesity for current smokers were lower than never smokers by 34% and 36%,
      respectively. The probability of abdominal obesity for heavy smokers was 31%
      lower than light smokers. We did not observe significant associations between
      smoking intensity and general obesity. CONCLUSIONS: Current smokers compared to
      never smokers were less likely to be obese. The reverse association between
      smoking and obesity; however, should not be interpreted as a causal relationship.

PMID- 29445048
TI  - Impact of Body Mass Index on Arterial Stiffness in Young Prehypertensives: A
      Cross Sectional Study.
AB  - BACKGROUND: Obesity and hypertension pose a big threat to public health.
      Targeting the prehypertension stage to evaluate the vascular damage due to
      obesity can help us to plan early interventions. STUDY DESIGN: A cross-sectional
      study. METHODS: This study  as a part of the medical heath checkup program was
      conducted by the Medical College in Puducherry, India on all medical students of
      age group 18-25 years. Blood pressure (BP) recordings and body mass index (BMI)
      were classified into following four groups: Group1: Normotensives with normal BMI
      (n=109); Group 2: Normotensives with higher BMI (n=89); Group 3: Prehypertensive
      subjects with normal BMI (n=50); and Group 4: Prehypertensive subjects with
      higher BMI (n=99). Arterial stiffness, body fat composition, and lipid profile
      were evaluated. Correlation of arterial stiffness indices with BMI, BP, body fat,
      visceral fat, lipid profile were done using Pearson's correlation and the
      contribution of BMI to arterial stiffness was assessed using univariate
      regression analysis. RESULTS: BMI, arterial stiffness, body fat, visceral fat,
      total cholesterol and total triglyceride showed a significant increase in
      prehypertensive group with higher BMI as compared to other groups. BMI showed
      significant correlation with arterial stiffness (P<0.0001) and found to be an
      independent contributing factor for arterial stiffness development in
      prehypertensives. CONCLUSIONS: Vascular damage was seen in the prehypertensive
      stage itself and was more pronounced in individuals with higher BMI.

PMID- 29445049
TI  - Prevalence and Predictors of Internet Addiction among College Students in Sousse,
      Tunisia.
AB  - BACKGROUND: Internet represents a revolution in the world of technology and
      communication all over the world including Tunisia. However, this technology has
      also introduced problematic use, especially among students. The current study
      aimed to determine the prevalence of Internet addiction among college students
      and its predictors in the region of Sousse, Tunisia. STUDY DESIGN: A cross
      sectional study. METHODS: The current study was conducted in the colleges of
      Sousse, Tunisia in 2012-2013. A self-administrated questionnaire was used to
      collect data from 556 students in 5 randomly selected colleges from the region.
      Collected data concerned socio-demographic characteristics, substances use and
      internet addiction using the Young Internet Addiction Test. RESULTS: The response
      rate was 96%. The mean age of participants was 21.8+/-2.2 yr. Females represented
      51.8% of them. Poor control of internet use was found among 280 (54.0%; CI95%:
      49.7, 58.3%) participants. Low education levels among parents, the young age,
      lifetime tobacco use and lifetime illicit drugs use were significantly associated
      with poor control of internet use among students (P<0.001). While, the most
      influential factor on internet use among them was under-graduation with an
      adjusted odds ratio of 2.4 (CI95%: 1.7, 3.6). CONCLUSIONS: Poor control of
      internet use is highly prevalent among the college students of Sousse especially
      those under graduate. A national intervention program is required to reduce this
      problem among youth. A national study among both in-school and out-of-school
      adolescents and young people would identify at-risk groups and determine the most
      efficient time to intervene and prevent internet addiction.

PMID- 29445050
TI  - Has the Financial Protection Been Materialized in Iranian Health System?
      Analyzing Household Income and Expenditure Survey 2003-2014.
AB  - BACKGROUND: The financial protection against catastrophic and impoverishing
      health expenditures is one of the main aspects of the universal health coverage.
      This study aimed to present a clear picture of the financial protection situation
      in Iran from 2003-2014. STUDY DESIGN: This is an analytical study on secondary
      data of Statistical Center of Iran (SCI). The study has some policy implications
      for policy makers; therefore, it is an applied one. METHODS: Data related to the
      Iranian rural and urban household payments on health expenditures was obtained
      from annual surveys of the SCI. WHO researchers' approach was used to calculate
      the Fairness of Financial Contribution Indicator (FFCI), the headcount and
      overshoot ratios of catastrophic and impoverishing health expenditures. A
      logistic regression was conducted to identify the determinants of probability of
      occurrence of catastrophic health expenditure among Iranian households in 2014.
      RESULTS: The mean of FFCI for rural and urban households was 0.854 (0.41) and
      0.867 (0.32), respectively. The average headcount ratios of catastrophic and
      impoverishing health expenditures were 1.32% (0.24) and 0.33% (P=0.006) for rural
      households and 1.4% (0.6) and 0.28% (P=0.001) for urban households. Concerning
      rural households, the overshoot of catastrophic and impoverishing health
      expenditures was 14.94% (P=0.001) and 7.22% (0.53); it was 15.59% (1.54) and
      7.76% (0.52) for urban households. CONCLUSIONS: No significant and considerable
      change was found in the headcount ratios of catastrophic and impoverishing health
      expenditure and in their overshoot or gap amounts. This suggested a lack of well
      designed and effective schemes for materializing the financial protection in
      Iran.

PMID- 29445051
TI  - Socioeconomic Inequalities in Poor Health-Related Quality of Life in Kermanshah,
      Western Iran: A Decomposition Analysis.
AB  - BACKGROUND: Socioeconomic status (SES) is an important determinant of health
      related quality of life (HRQoL). We aimed to quantify socioeconomic-related
      inequality in poor-HRQoL among adults in Kermanshah, western Iran. STUDY DESIGN:
      A cross-sectional study. METHODS: Overall, 1730 adults (18-65 yr) were selected
      using convenience sampling from Kermanshah, Iran. A self-administrated
      questionnaire was used to collect data on socio-demographic characteristics, SES,
      lifestyle factors and HRQoL of participants over the period between May and Aug
      2017. The concentration curve and concentration index (C) were used to illustrate
      and measure wealth-related inequality in poor-HRQoL. Additionally, we decomposed
      the C index to identify factors explaining wealth-related inequality in poor
      HRQoL. RESULTS: The overall prevalence of poor-HRQoL was 35.3% (95% confidence
      interval[CI]: 33.1%, 37.6%). The poor-HRQoL was mainly concentrated among the
      poor adults (C=-0.256, 95% CI: -0.325, -0.187). Poor-HRQoL was concentrated among
      men (C=-0.256, 95% CI: -0.345, -0.177) and women (C=-0.261, 95% CI: -0.310, 
      0.204). Wealth, physical inactivity, the presence of chronic health condition(s),
      lack of health insurance coverage were the main factors contributing to the
      concentration of poor-HRQoL among socioeconomically disadvantaged adults.
      CONCLUSIONS: Socioeconomic-related inequalities in poor-HRQoL among adult should
      warrant more attention. Policies should be designed to not only improve HRQoL
      among adults but also reduce the pro-rich distribution of HRQoL among adults in
      Kermanshah.

PMID- 29445052
TI  - Increase in breath hydrogen concentration was correlated with the main pancreatic
      duct stenosis.
AB  - BACKGROUND: Hydrogen is produced from unabsorbed carbohydrates in the intestine
      through degradation and metabolism by hydrogenase of intestinal bacteria. The
      hydrogen is then partially diffused into blood flow and released and detected in
      exhaled breath. Pancreatic juice production is decreased in patients with reduced
      pancreatic exocrine function, including those with pancreatic cancer, thus
      decreasing digestion and absorption of nutrients including carbohydrates, which
      may increase undigested carbohydrates in the intestine and increase breath
      hydrogen concentration (BHC). The aim of this study was to investigate the
      association between BHC and pancreatic diseases. METHODS: A retrospective study
      was designed and 68 patients underwent morning fasting breath hydrogen test.
      Since there is no clear standard, normal BHC, the median of the measured values
      from the subjects (9 ppm) was adopted as the standard. The subjects were
      classified into those with a value exceeding the median (BHC high group: 32
      patients) and a value equal to or below the median (BHC low group: 36 patients).
      Patients characteristics, blood test results and imaging findings characteristic
      of pancreatic diseases were compared between the groups. RESULTS: The age was
      significantly higher (P = 0.010) and the incidences of pancreatic ductal
      adenocarcinoma and autoimmune pancreatitis were significantly higher (P = 0.018
      and P = 0.004, respectively) in the BHC high group. With respect to the blood
      test items, the Alb level was significantly lower in the BHC high group (P =
      0.005). With respect to the characteristic imaging findings of pancreatic
      diseases, the proportions of patients with pancreatic enlargement, the main
      pancreatic duct (MPD) stenosis, and the MPD dilatation were significantly higher
      in the BHC high group (P = 0.022, P < 0.001, and P = 0.002, respectively). On
      univariate analysis, only the MPD stenosis was extracted as an independent factor
      (P = 0.014). CONCLUSION: It was suggested that the fasting BHC is associated with
      pancreatic diseases causing stenosis of the MPD, including pancreatic cancer
      (UMIN000020777).

PMID- 29445053
TI  - SPIRAL2 Stabilises Endoplasmic Microtubule Minus Ends in the Moss Physcomitrella
      patens.
AB  - Stabilisation of minus ends of microtubules (MTs) is critical for organising MT
      networks in land plant cells, in which all MTs are nucleated independent of
      centrosomes. Recently, Arabidopsis SPIRAL2 (SPR2) protein was shown to localise
      to plus and minus ends of cortical MTs, and increase stability of both ends.
      Here, we report molecular and functional characterisation of SPR2 of the basal
      land plant, the moss Physcomitrella patens. In protonemal cells of P. patens,
      where non-cortical, endoplasmic MT network is organised, we observed SPR2 at
      minus ends, but not plus ends, of endoplasmic MTs and likely also of phragmoplast
      MTs. Minus end decoration was reconstituted in vitro using purified SPR2,
      suggesting that moss SPR2 is a minus end-specific binding protein (-TIP). We
      generated a loss-of-function mutant of SPR2, in which frameshift-causing
      deletions/insertions were introduced into all four paralogous SPR2 genes by means
      of CRISPR/Cas9. Protonemal cells of the mutant showed instability of endoplasmic
      MT minus ends. These results indicate that moss SPR2 is a MT minus end
      stabilising factor.Key words: acentrosomal microtubule network, microtubule minus
      end, P. patens, CAMSAP/Nezha/Patronin.

PMID- 29445055
TI  - An Inappropriate Shock Case Early after Implantation of a Subcutaneous Cardiac
      Defibrillator by Subcutaneous Entrapped Air.
AB  - A 17-year-old woman was resuscitated from cardiac arrest due to ventricular
      fibrillation and was diagnosed with concealed long QT syndrome. She underwent
      subcutaneous implantable cardiac defibrillator (S-ICD) implantation at our
      hospital. The device electrogram immediately after implantation was normal. Four
      days after implantation, she received an inappropriate shock. The device
      interrogation revealed a continuous baseline shift and frequent oversensing for
      low amplitude signals, followed by a shock. A chest radiograph in the orthogonal
      view showed entrapped subcutaneous air surrounding the distal electrode.
      Entrapped subcutaneous air can cause inappropriate shocks in the early period
      after S-ICD implantation.

PMID- 29445054
TI  - Comparison of Drug Metabolism and Its Related Hepatotoxic Effects in HepaRG,
      Cryopreserved Human Hepatocytes, and HepG2 Cell Cultures.
AB  - Differentiated HepaRG cells maintain liver-specific functions such as drug
      metabolizing enzymes. In this study, the feasibility of HepaRG cells as a human
      hepatocyte model for in vitro toxicity assessment was examined using selected
      hepatotoxic compounds. First, basal drug-metabolizing enzyme activities (CYP1A2,
      CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, uridine 5'-diphospho
      glucuronosyltransferase [UGT], and sulfotransferases [SULT]) were measured in
      HepaRG, human hepatocytes, and HepG2 cells. Enzyme activities in differentiated
      HepaRG cells were comparable to those in human hepatocytes and much higher than
      those in HepG2 cells, except for SULT activity. Second, we examined the
      cytotoxicity of hepatotoxic compounds, acetaminophen (APAP), aflatoxin B1 (AFB1),
      cyclophosphamide (CPA), tamoxifen (TAM), and troglitazone (TGZ) in HepaRG cells
      and human hepatocytes. AFB1- and CPA-induced cytotoxicities against HepaRG cells
      were comparable to those against human hepatocytes. Furthermore, the
      cytotoxicities of these compounds were inhibited by 1-aminobenzotriazole (ABT), a
      broad CYP inhibitor, in both cells and were likely mediated by metabolic
      activation by CYP. Finally, toxicogenomics analysis of HepG2 and HepaRG cells
      after exposure to AFB1 and CPA revealed that numerous p53-related genes were
      upregulated- and the expression of these genes was greater in HepaRG than in
      HepG2 cells. These results suggest that gene expression profiles of HepaRG cells
      were affected more considerably by the toxic mechanisms of AFB1 and CPA than the
      profiles of HepG2 cells were. Therefore, our investigation shows that HepaRG
      cells could be useful human hepatic cellular models for toxicity studies.

PMID- 29445056
TI  - Decreased Serum Relaxin-2 Is Correlated with Impaired Islet beta-Cell Function in
      Patients with Unstable Angina and Abnormal Glucose Metabolism.
AB  - Circulating relaxin (RLX) is altered in patients with diabetes mellitus (DM) or
      cardiovascular diseases. This study was designed to evaluate the changes of RLX
      in patients with unstable angina (UA) complicated with various categories of
      abnormal glucose metabolism.Patients who confirmed UA by angiographic and
      clinical standard were grouped according to the glucose metabolism status with
      oral glucose tolerance test (OGTT) and medical history categorized as normal,
      prediabetes, newly diagnosed type 2 DM (T2DM), and previously diagnosed T2DM.
      Serum RLX-2 was measured and islet beta-cell function was evaluated. The severity
      of the coronary arterial lesions was evaluated with Syntax Scores.Serum RLX-2 was
      significantly higher in UA patients with prediabetes (median [quartiles]: 9.87
      [7.48, 32.58] pg/mL) and newly diagnosed T2DM (18.36 [9.52, 48.08] pg/mL),
      compared with those with normal glucose tolerance (6.24 [4.02, 7.27] pg/mL, both
      P < 0.05). Interestingly, UA patients with previously diagnosed T2DM exhibited
      lower RLX-2 levels (4.17 [3.23, 5.72] pg/mL) compared with those with normal
      glucose tolerance (P < 0.05). Subsequent analyses indicated that serum RLX-2 was
      positively associated with parameters of islet beta-cell function, C-peptide, and
      fasting insulin levels; however, it was negatively associated with the levels of
      fasting glucose, 2-hour postprandial blood glucose, HbA1c, and insulin
      sensitivity, suggesting a potential protective role of RLX-2 during abnormal
      glucose metabolism in UA patients. Serum RLX-2 was not correlated with the Syntax
      Scores in these patients.Serum RLX-2 is a potential marker for UA patients with
      early glucose metabolism abnormality, and increased RLX-2 level was correlated
      with preserved islet beta-cell function.

PMID- 29445057
TI  - Utility of Fluid Assessment Based on the Intrathoracic Impedance Monitoring in a
      Peripartum Woman with Heart Disease.
AB  - Recently, implantable cardioverter-defibrillators (ICD) have become capable of
      monitoring intrathoracic impedance to detect an increased fluid volume and heart
      failure. Pregnancy is a well-known cause of an increased body fluid volume;
      however, it is not clear whether the measurement of intrathoracic impedance by
      ICD is clinically useful for precisely detecting heart failure in pregnant women.
      We herein report the case of a 39-year-old woman with an ICD that had been
      implanted after an event of ventricular fibrillation due to severe aortic
      regurgitation with a bicuspid aortic valve. Elevated right ventricular pressure
      and brain natriuretic peptide levels were detected at 37 weeks of gestation and
      postpartum. At the same time, the ICD's stored fluid index gradually increased
      and exceeded the threshold on the 10th day after delivery. She was treated with
      diuretics and recovered from postpartum heart failure. The physiological volume
      changed in the perinatal period, but we were still able to detect heart failure
      by ICD. Intrathoracic impedance monitoring is effective in the perinatal field.

PMID- 29445058
TI  - Nonfasting Glucose and Incident Stroke and Its Types - The Circulatory Risk in
      Communities Study (CIRCS).
AB  - BACKGROUND: The effect of postprandial glucose on the risk of cardiovascular
      disease has been emphasized, but it is controversial whether nonfasting glucose
      is related to incident stroke and its types.Methods and Results:We investigated
      the associations of nonfasting glucose with incident stroke and its types among
      7,198 participants aged 40-74 years from the Circulatory Risk in Communities
      Study, enrolled in 1995-2000. We estimated multivariable hazard ratios (HR) using
      Cox proportional hazard models. Over a median follow-up of 14.1 years, 291 cases
      of total stroke (ischemic strokes: 191 including 109 lacunar infarctions) were
      identified. Nonfasting glucose concentration was associated with greater risk of
      incident total stroke, ischemic stroke and lacunar infarction when modeled
      categorically (for prediabetic type: 7.8-11.0 mmol/L vs. normal type: <7.8 mmol/L
      among all subjects, HR for lacunar infarction was 2.02, 95% confidence interval
      (CI): 1.19, 3.43) or continuously (per one standard deviation increment among all
      subjects, HR for lacunar infarction was 1.29, 95% CI: 1.15, 1.45). Diabetic type
      showed similar results. Population attributable fractions of nonfasting
      hyperglycemia were 13.2% for ischemic stroke and 17.4% for lacunar infarction.
      CONCLUSIONS: Nonfasting glucose concentration, either as a diagnosis of
      prediabetic and diabetic types or as a continuous variable, proved to be an
      independent predictor significantly attributed to incident total stroke,
      especially ischemic stroke and lacunar infarction, in the general population.

PMID- 29445059
TI  - Liver Cirrhosis and/or Hepatocellular Carcinoma Occurring Late After the Fontan
      Procedure - A Nationwide Survey in Japan.
AB  - BACKGROUND: Fontan-associated liver disease (FALD) is an important late
      complication involving liver dysfunction, such as liver cirrhosis (LC) and
      hepatocellular carcinoma (HCC), in patients undergoing the Fontan procedure.
      However, the prevalence, clinical manifestation, and methods of diagnosis of FALD
      are still not well established.Methods and Results:This study comprised 2
      nationwide surveys in Japan. First, the prevalence of LC and/or HCC in patients
      undergoing the Fontan procedure was determined. Second, clinical manifestations
      in patients with LC and/or HCC were analyzed, along with data from blood tests,
      echocardiography, and right heart catheterization. In the 1st survey, of the
      2,700 patients who underwent the Fontan procedure, 31 were diagnosed with LC
      and/or HCC (1.15%), and 5 died due to liver diseases (mortality: 0.19%). In the
      2nd survey, data were collected from 17 patients (12 with LC, 2 with HCC, and 3
      with LC+HCC. Of these 17 patients, 5 died (mortality: 29.4%). The mean age at
      diagnosis of LC and HCC was 23 and 31 years, respectively. Computed tomography
      followed by ultrasound was most frequently used for diagnosis. Blood tests
      revealed low platelet counts, increased hemoglobin, aspartate aminotransferase,
      gamma-guanosine triphosphate, and total bilirubin levels, and an elevated
      international normalized ratio of prothrombin time. CONCLUSIONS: LC and/or HCC in
      patients undergoing the Fontan procedure were not rare late complications and
      were associated with high mortality rates.

PMID- 29445060
TI  - Clinical Usefulness of Wearable Cardioverter Defibrillator (WCD) and Current
      Understanding of Its Clinical Indication in Japan.
AB  - Prevention of sudden cardiac death (SCD) has become an important issue in today's
      cardiovascular field, together with various developments in secondary prevention
      of basic cardiac diseases. The importance of the implantable cardioverter
      defibrillator (ICD) is now widely accepted because it has exhibited significant
      improvement in patients' prognoses in ischemic and non-ischemic cardiovascular
      diseases. However, there is an unignorable gap between the ICD indication in the
      guidelines and real-world high-risk patients for SCD, especially in the acute
      recovery phase of cardiac injury. Although various studies have demonstrated a
      clinical benefit of defibrillation devices, the studies of immediate ICD use in
      the acute recovery phase have failed to exhibit a benefit in patients from the
      point of the view of a decrease in total deaths. To bridge this gap, the wearable
      cardioverter defibrillator (WCD) provides a safer observation period in the acute
      phase and eliminates inappropriate overuse of ICD in the subacute phase. Here, we
      discuss the usefulness of the WCD and current understanding of its indications
      based on various clinical data. In conclusion, WCD is a feasible bridge to
      therapy and/or safe observation for patients at high risk of SCD, especially in
      the acute recovery phase of cardiac diseases.

PMID- 29445061
TI  - The Prophylactic Effect of Anti-influenza Agents for an Influenza Outbreak in a
      University Hospital.
AB  - Objective From November 24 to December 9, 2013, an outbreak of the influenza
      (flu) A (H3) virus occurred in a tertiary-care university hospital (1,014 beds).
      We herein report the prophylactic effect of anti-flu agents for controlling the
      flu outbreak. Methods We administered pre- or post-exposure prophylaxis with anti
      flu agents in flu outbreak. To test the effectiveness of prophylaxis in a flu
      outbreak, we used the posterior mean of the reproductive value during the pre-
      and post-intervention period. We also simulated the probability distribution of
      new flu cases. We performed an analysis to quantify the strength of the
      intervention effect. Results A total of 97 people were diagnosed with flu before
      the intervention, and 7 were diagnosed after the intervention. A molecular
      analysis of the flu virus revealed that this outbreak was due to the flu A (H3)
      virus. A total of 3,702 people received prophylaxis. There was a significant
      reduction in the reproductive value from 1.89 [95% confidence interval (CI), 1.59
      to 2.24] to 0.65 (95% CI, 0.02 to 1.00) after the intervention (p<0.001).
      Conclusion Prophylaxis with anti-flu agents, along with prompt identification and
      isolation of infected individuals, was effective in reducing the impact of a flu
      outbreak in a hospital.

PMID- 29445062
TI  - Associated Factors with Left Atrial Enlargement in Patients with Acute Ischemic
      Stroke.

PMID- 29445063
TI  - Associated Factors with Left Atrial Enlargement in Patients with Acute Ischemic
      Stroke.

PMID- 29445064
TI  - The validity of anesthetic protocols for the surgical procedure of castration in
      rats.
AB  - To achieve surgical anesthesia in animal experimentation, it is necessary to
      select the appropriate anesthetic protocol by considering its pharmacological
      properties and the surgical procedure to be performed. However, few studies have
      investigated the validity of anesthetic protocols under surgical conditions in
      small rodents. The present study aimed to clarify the pharmacological properties
      of 4 anesthetic protocols during the surgical procedure of castration in rats.
      Eight-week-old male Wistar rats were anesthetized with anesthetics, including the
      combination of ketamine and xylazine (K/X), the combination of medetomidine,
      midazolam, and butorphanol (M/M/B), isoflurane, and sevoflurane. Castration was
      performed under each anesthesia, and anesthetic depth and times were assessed, as
      were vital signs. The injectable anesthetics were investigated at standard and
      high doses. The concentration of inhalant anesthetics was adjusted to 1.5 minimum
      alveolar concentration (MAC). K/X at both doses demonstrated sufficient
      anesthetic depth with rapid induction and recovery. However, bradycardia and
      hypothermia were prominent in high-dose K/X, indicating that the standard-dose is
      more appropriate for surgical anesthesia in castration procedures. M/M/B
      demonstrated high anesthetic sensitivity variation in individual animals. In
      contrast to injectable anesthetics, inhalant anesthetics provided stable
      anesthetic depth with less cardiorespiratory influence. Sevoflurane did not lead
      to a significant decrease in rectal temperature during the anesthetic period.
      Results of the present study revealed the optimal dose and pharmacological
      features of several anesthetic protocols for castration, and may contribute to
      the standardization of surgical anesthesia in rats.

PMID- 29445065
TI  - Questionnaire Survey From the Viewpoint of Concordance in Patient and Physician
      Satisfaction Concerning Hypertensive Treatment in Elderly Patients - Patients
      Voice Study.
AB  - BACKGROUND: Patient-physician concordance is an important concern in the
      treatment of elderly patients with hypertension (HT). Treatment that considers
      concordance is necessary for mutual understanding and therapeutic satisfaction
      between patients and physicians. However, there have been no studies addressing
      concordance that objectively analyzed both patient and physician satisfaction
      before and after treatment.Methods and Results:An exploratory open-label,
      multicenter, intervention study was conducted. Patients with HT undergoing
      treatment with angiotensin-receptor blocker (ARB) or a calcium-channel blocker
      (CCB) monotherapy were enrolled. Medication was switched to an ARB/CCB
      combination tablet and taken for 12 weeks. Physicians and patients participated
      in satisfaction surveys concerning treatment. Discrepancies in satisfaction
      levels between patients and physicians were found at baseline for the following
      survey items: treatment, involvement in treatment, understanding of HT, reliance,
      medication, and blood pressure. After treatment, the satisfaction levels of both
      patients and physicians increased; discrepancies in satisfaction between the
      groups also improved. CONCLUSIONS: The rates of satisfaction were relatively
      higher for patients compared with physicians at baseline. After HT treatment
      addressing concordance, both patient and physician satisfaction rates and the gap
      in satisfaction rates between patients and physicians improved. This indicates
      that addressing concordance has clinical significance in the treatment of elderly
      HT patients. (UMIN000017270).

PMID- 29445066
TI  - Epidemiology of Pediatric Out-of-Hospital Cardiac Arrest at School - An
      Investigation of a Nationwide Registry in Japan.
AB  - BACKGROUND: A better understanding of the epidemiology of pediatric out-of
      hospital cardiac arrest (OHCA) occurring in school settings is important to
      establish an evidence-based strategy for prevention and better prognosis.Methods
      and Results:The Stop and Prevent cardIac aRrest, Injury, and Trauma in Schools
      (SPIRITS) is a nationwide prospective observational study linking databases from
      2 nationally representative registries, the Injury and the Accident Mutual Aid
      Benefit System of The Japan Sport Council and the All-Japan Utstein Registry of
      the Fire and Disaster Management Agency. Using these databases, we described the
      detailed characteristics and outcomes of pediatric OHCAs that occurred in school
      settings in Japan between 2009 and 2014. During the 6-year study period, 295 OHCA
      cases were confirmed. Overall incidence rate was 0.4 per 100,000 students per
      year. The majority of OHCA cases had a cardiac origin (71%), occurred during
      exercise (65%), were witnessed by bystanders (70%), and received bystander
      initiated cardiopulmonary resuscitation (73%). In approximately one-third of
      cases the student was defibrillated by public-access automated external
      defibrillator (38%). The proportion of patients with 1-month survival and a
      favorable neurological outcome was 34% among all OHCAs and 43% among OHCAs of
      cardiac origin. CONCLUSIONS: In Japan, approximately 50 pediatric cases of OHCA
      consistently occur yearly in school settings. The majority of students received
      basic life support from bystanders, and patients with OHCA of cardiac origin had
      a relatively good prognosis.

PMID- 29445067
TI  - Circulating Fatty Acid-Binding Protein 4 Concentration Predicts the Progression
      of Carotid Atherosclerosis in a General Population Without Medication.
AB  - BACKGROUND: Fatty acid-binding protein 4 (FABP4), which is expressed in both
      adipocytes and macrophages, is secreted from the cells and acts as an adipokine.
      An elevated circulating FABP4 level is associated with insulin resistance and
      atherosclerosis.Methods and Results:We investigated the causative association
      between FABP4 level and progression of atherosclerosis in subjects of the Tanno
      Sobetsu Study, a population-based cohort. In 281 subjects without medication
      (male/female: 109/172) in the year 2010 or 2013, the carotid intima-media
      thickness (CIMT) assessed using carotid ultrasonography was significantly
      correlated with age, adiposity, blood pressure, renal dysfunction and levels of
      cholesterol, triglycerides, fasting glucose, HbA1c and FABP4 (r=0.331, P<0.001).
      Multiple regression analysis demonstrated that age, sex and FABP4 concentration
      were independent predictors of CIMT. A total of 78 (male/female: 29/49) of the
      156 subjects in 2010 underwent carotid ultrasonography again in 2013. The change
      in CIMT each year during that 3-year period (mean+/-SD: 3.8+/-22.3 um/year) was
      positively correlated with basal levels of high-sensitivity C-reactive protein
      (hsCRP) (r=0.231, P=0.046) and FABP4 (r=0.267, P=0.018) in 2010. After adjustment
      for age, sex and hsCRP level, the basal FABP4 level was independently associated
      with the change in CIMT per year. CONCLUSIONS: FABP4 concentration is an
      independent predictor of the progression of carotid atherosclerosis.

PMID- 29445068
TI  - Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Its histological
      characteristics, such as progressive intrahepatic bile duct destruction,
      cholestasis, and liver cirrhosis, are caused by the body's autoimmune disorders.
      Interleukin (IL)-35 has two subunits (p35 and Ebi3) and is a member of the IL-12
      family of heterodimeric cytokines. IL-35 has immunosuppressive functions and
      plays an important role in many autoimmune diseases. In this study, we compared
      plasma levels of IL-35 and relative mRNA expression levels of p35 and Ebi3 in
      peripheral blood mononuclear cells (PBMCs) from 70 PBC patients and 70 healthy
      individuals. The results showed that the relative expression levels of Ebi3 mRNA
      were lower in PBMCs from PBC patients than in PBMCs from healthy individuals,
      whereas the levels of p35 mRNA were similar in both groups. Plasma IL-35
      concentrations were lower in patients with PBC than in healthy individuals.
      Plasma levels were higher in PBC patients at an advanced stage compared to
      patients at an early stage. Variable plasma levels with different stages were
      also found in transforming growth factor beta (TGF-beta), which is mainly
      produced by regulatory T cells (Tregs). IL-35 and TGF-beta levels were positively
      correlated with each other, and IL-35 was capable of promoting the inhibitory
      functions of Tregs in PBC patients at both the early and late stages of disease.
      Lower plasma IL-35 levels were accompanied by higher levels of typical clinical
      parameters, such as alkaline phosphatase, or of proinflammatory cytokines, such
      as interferon-gamma (IFN-gamma), in PBC patients (P < 0.05 for each). We propose
      that IL-35 may be involved in the pathogenesis of PBC and could be a potential
      biomarker for diagnosing this disease.

PMID- 29445069
TI  - Expression and distribution of the zinc finger protein, SNAI3, in mouse ovaries
      and pre-implantation embryos.
AB  - The Snail gene family includes Snai1, Snai2, and Snai3 that encode zinc finger
      containing transcriptional repressors in mammals. The expression and localization
      of SNAI1 and SNAI2 have been studied extensively during folliculogenesis,
      ovulation, luteinization, and embryogenesis in mice. However, the role of SNAI3
      is unknown. In this study, we investigated the expression of SNAI3 during these
      processes. Our immunohistochemistry data showed that SNAI3 first appeared in
      oocytes by postnatal day (PD) 9. Following this, SNAI3 was found to be expressed
      consistently in theca and interstitial cells, along with oocytes. In gonadotropin
      treated immature mice, the expression of SNAI3 did not change significantly
      during follicular development. The expression of SNAI3 was reduced during
      ovulation, after which it increased gradually during luteinization. Similar
      results were obtained from western blot analyses. Furthermore, real-time
      polymerase chain reaction (RT-PCR) analyses revealed varying mRNA levels of
      different Snail factors at a given time in gonadotropin-induced ovaries. During
      early embryo cleavage, SNAI3 was localized to the nucleus, except the nucleolus
      at the germinal vesicle and one-cell stages. From two- to eight-cell stages,
      SNAI3 was localized only to the nucleolus. Thereafter, SNAI3 was detected only in
      the cytoplasm, except during the blastocyst stage when it was localized to the
      nucleus of the trophectoderm and the inner cell mass. RT-PCR results showed that
      the expression of Snail superfamily genes was decreased during the blastocyst
      stage. From the eight-cell to morula stage, when compaction occurs that is a
      prerequisite for blastocyst formation, Snai3 mRNA was expressed at very low
      levels and was opposite to the highest expression level of the compaction-related
      gene, E-cadherin, at the eight-cell stage. Taken together, our results suggest
      that SNAI3 likely plays some roles during folliculogenesis, luteinization, and
      early embryonic development.

PMID- 29445070
TI  - Development to term of sheep embryos reconstructed after inner cell
      mass/trophoblast exchange.
AB  - Here we report in vitro and term development of sheep embryos after the inner
      cell mass (ICM) from one set of sheep blastocysts were injected into the
      trophoblast vesicles of another set. We also observed successful in vitro
      development of chimeric blastocysts made from sheep trophoblast vesicles injected
      with bovine ICM. First, we dissected ICMs from 35 sheep blastocysts using a
      stainless steel microblade and injected them into 29 re-expanded sheep
      trophoblastic vesicles. Of the 25 successfully micromanipulated trophoblastic
      vesicles, 15 (51.7%) re-expanded normally and showed proper ICM integration. The
      seven most well reconstructed embryos were transferred for development to term.
      Three ewes receiving manipulated blastocysts were pregnant at day 45 (42.8%), and
      all delivered normal offspring (singletons, two females and one male, average
      weight: 3.54 +/- 0.358 kg). Next, we monitored in vitro development of sheep
      trophoblasts injected with bovine ICMs. Of 17 injected trophoblastic vesicles, 10
      (58.8%) re-expanded after 4 h in culture, and four (40%) exhibited integrated
      bovine ICM. Our results indicate that ICM/trophoblast exchange is feasible,
      allowing full term development with satisfactory lambing rate. Therefore, ICM
      exchange is a promising approach for endangered species conservation.

PMID- 29445071
TI  - A case report of thyroid metastasis from p16-positive oropharyngeal squamous cell
      carcinoma.
AB  - Thyroid metastasis from head and neck squamous cell carcinoma (SCC) is a very
      rare form of rarely observed metastatic thyroid tumor. We herein report a case of
      thyroid metastasis from oropharyngeal SCC (OSCC). The patient was a 68-year-old
      male diagnosed with p16-positive tonsillar OSCC on the right side with multiple
      lymph node metastases and a thyroid mass, which was determined as metastatic p16
      positive OSCC by immunohistochemistry of specimens collected by fine-needle
      aspiration cytology (FNAC). He received one cycle of induction chemotherapy
      followed by concurrent chemoradiotherapy. No visible primary lesions were
      observed after treatment. The disappearance of the tonsillar lesion was
      considered to be a complete response by the magnetic resonance imaging (MRI) and
      positron emission tomography-computed tomography (PET-CT). The thyroid lesion was
      also decreased, but a solid lesion with unclear boundaries in the right thyroid
      lobe remained. Therefore, the patient underwent total thyroidectomy to remove any
      residual tumor. Postoperative pathological evaluation revealed no residual viable
      carcinoma cells in the resected specimen. As illustrated in this case,
      immunohistochemistry of the FNAC specimen for p16 was successful in determining
      the thyroid tumor as a metastatic lesion from the oropharynx. Although radical
      radiotherapy might be sufficient to control thyroid gland metastasis of OSCC, in
      this case, early-stage remedial surgery was thought to be necessary for a secure
      radical cure.

PMID- 29445072
TI  - Molar eruption and identification of the eastern grey kangaroo (Macropus
      giganteus) at different ages.
AB  - To treat dental disorders and estimate age, it is important that veterinarians
      understand teeth eruption sequence for the animal in question. Few dental images
      of the eastern grey kangaroo have been published. In the present study,
      radiographic imagings of 29 kangaroos, ranging in age from 12 months to 10 years
      9 months, was used to surveil the replacement of premolars and the eruption of
      molars. These images revealed eruption patterns in five stages, while the second
      and third deciduous premolars were shed non-systematically. Furthermore, the
      third premolars and fourth molars erupted in the mandible earlier than in the
      maxilla, which may contribute to the frequency of mandibular dental disorders.

PMID- 29445073
TI  - Adiponectin deficiency-induced diabetes increases TNFalpha and FFA via
      downregulation of PPARalpha.
AB  - Expression of peroxisome proliferator-activated receptor (PPAR) alpha was
      investigated in adiponectin knockout mice to elucidate the relationship between
      PPARalpha and adiponectin deficiency-induced diabetes. Adiponectin knockout (Adp
      /-) mice were generated by gene targeting. Glucose tolerance test (GTT), insulin
      tolerance test (ITT), and organ sampling were performed in Adp-/- mice at the age
      of 10 weeks. PPARalpha, insulin, triglyceride, free fatty acid (FFA), and tumor
      necrosis factor alpha (TNFalpha) were analyzed from the sampled organs. Adp-/-
      mice showed impaired glucose tolerance and insulin resistance. Additionally,
      PPARalpha levels were decreased and plasma concentration of triglyceride, FFA and
      TNFalpha were increased. These data may indicate that insulin resistance in Adp-/
      mice is likely caused by an increase in concentrations of TNFalpha and FFA via
      downregulation of PPARalpha.

PMID- 29445074
TI  - Intrapancreatic accessory spleen in a harbor porpoise (Phocoena phocoena).
AB  - The occurrence of accessory spleens in cetacean species is high yet confirmed
      reports of intrapancreatic accessory spleen, a congenital malformation, remain
      undescribed. The current study provides the gross, microscopical, histochemical
      and immunohistochemical features of an intrapancreatic accessory spleen in a
      harbor porpoise (Phocoena phocoena). Grossly, a 17 * 18 * 9 mm well-demarcated,
      dark brown to red mass expanded the left pancreatic lobe. Microscopically, this
      mass consisted of mature splenic tissue interspersed with exocrine pancreatic
      acini. Intrapancreatic accessory spleens should be considered in the list of
      differential diagnoses for intrapancreatic nodular lesions in cetaceans.

PMID- 29445075
TI  - Palladium-Catalyzed External-CO-Free Carbonylation of Aryl Bromides Using 2,4,6
      Trichlorophenyl Formate.
AB  - A practical Pd-catalyzed carbonylation of (hetero)aryl bromides using a
      crystalline carbon monoxide (CO) surrogate, 2,4,6-trichlorophenyl formate (TCPF),
      was developed. This reaction proceeds without the slow addition technique that
      was previously required and with a low catalyst loading (1 mol%). The utility of
      this Pd-catalyzed external-CO-free carbonylation using TCPF was demonstrated in
      the synthesis of a histone deacetylase inhibitor.

PMID- 29445077
TI  - Successful External Cardioversion via Fluoroscopic Electrode Positioning in
      Patients with Enlarged Trans-Thoracic Diameter.
AB  - BACKGROUND Atrial fibrillation is the most common cardiac arrhythmia. It
      increases the risk of stroke by at least five-fold and is associated with higher
      risk for mortality and morbidity. Therefore, prompt diagnosis and treatment is
      crucial. In addition to anti-coagulation therapy, electrical and pharmacological
      cardioversion to restore sinus rhythm remains the standard of care. The most
      common and effective method for electrical cardioversion is achieved with
      placement of electrodes in the anteroposterior position. CASE REPORT We present
      three cases of patients with initial unsuccessful cardioversion attempts for
      persistent atrial fibrillation. These patients had elevated body mass indices and
      large trans-thoracic diameters. Their initial external cardioversion via the
      conventional method was not successful for restoration of sinus rhythm. This
      failure may have been attributed to their body habitus. To ensure that the
      current would traverse through the atrial tissue, the electrode pads were applied
      using fluoroscopic guidance for adequate myocardial depolarization. CONCLUSIONS
      Optimal fluoroscopic placement of the electrode pads during external
      cardioversion procedure increases the odds of successful restoration of sinus
      rhythm when compared to the conventional method.

PMID- 29445076
TI  - Clinical Utility of Carotid Ultrasonography in the Prediction of Cardiovascular
      Events in Patients with Diabetes: A Combined Analysis of Data Obtained in Five
      Longitudinal Studies.
AB  - AIM: It remains unclear whether measures used in carotid ultrasonography such as
      the intima-media thickness (IMT) and ultrasonic tissue characterization of the
      carotid using the gray-scale median (GSM) can add prognostic information beyond
      the conventional cardiovascular risk markers in patients with diabetes. METHODS:
      This study employed a combined analysis of data obtained in five longitudinal
      studies including a total of 3263 patients with diabetes but without apparent
      cardiovascular disease (CVD) at baseline. The associations between carotid
      ultrasonography measures and the first occurrence of CVD (488 cases), which were
      defined as cardiovascular death, coronary artery diseases, stroke, or peripheral
      artery disease, were analyzed. RESULTS: Common carotid artery (CCA)-mean-IMT, CCA
      max-IMT, Max-IMT, plaque-GSM, and the presence of low-GSM echolucent plaques at
      baseline were prognostic factors for CVD even after adjustment for conventional
      risk factors. Time-dependent receiver-operating-characteristic (ROC) curve
      analysis indicated that the use of CCA-mean-IMT, CCA-max-IMT, and Max-IMT in
      addition to the conventional risk factors improved significantly the prediction
      of occurrence of CVD. Increments in the CCA-mean-IMT (hazard ratio [HR] 2.37 for
      every 0.1-mm/year increment [95% confidence interval [CI]: 1.63-3.47], p<0.001),
      Max-IMT (HR 1.51 for every 0.1-mm/year increment [95% CI: 1.07-2.14], p=0.020),
      and Mean-GSM (HR 0.22 for every 10-U/year increment [95% CI: 0.06-0.76], p=0.016)
      during the observation period were also prognostic factors for CVD even after
      adjusting for the baseline value of the respective measure. CONCLUSIONS: Addition
      of carotid ultrasonography measures to conventional risk factors significantly
      improved the stratification of patients by cardiovascular risk. Changes over time
      in carotid ultrasonography measures may be used as therapeutic outcome measures.

PMID- 29445078
TI  - miR-144 Potentially Suppresses Proliferation and Migration of Ovarian Cancer
      Cells by Targeting RUNX1.
AB  - BACKGROUND Ovarian cancer (OC) is one of the most common malignant diseases of
      the female reproductive system worldwide. Evidence has shown that microRNAs are
      involved in the development of ovarian cancer. miR-144, one of these microRNAs,
      has been found have upregulated expression in various human malignancies. The
      present study aimed to investigate the role miR-144 in ovarian cancer cell lines
      and to elucidate the mechanism involved. MATERIAL AND METHODS Human ovarian
      cancer cell lines (SKOV3/OVCAR3) and a normal ovarian cell line (IOSE80) were
      used to identify the miR-144 expression though qRT-PCR method. SKOV3/OVCAR3 cells
      were transfected with miR-144 mimics by Lipofectamine, and the proliferation,
      migration, and invasion ability of these cells were detected by MTT assay, wound
      healing assay, and Transwell assays, respectively. MMP2 and MMP9 expression were
      detected at mRNA and protein levels. The results of dual luciferase reporter
      assay confirmed that miR-144 could down-regulate RUNX1 expression level. Finally,
      the expression of runt-related transcription factor 1 (RUNX1) was examined using
      qRT-PCR and Western blot analysis. RESULTS Our results demonstrate that the
      expression level of miR-144 was downregulated in SKOV3/OVCAR3 compared to IOSE80,
      and we found that miR-144 suppresses the proliferation and migration of ovarian
      cancer cells. Moreover, RUNX1 was predicted and confirmed to be a target of miRNA
      144. Additionally, after 48-h transfection with miR-144 mimics, the expression of
      RUNX1 was downregulated in OC cells. CONCLUSIONS miR-144 mimics can inhibit the
      proliferation and migration of ovarian cancer cells though regulating the
      expression of RUNX1.

PMID- 29445079
TI  - Seropositivity of Hepatitis A in Children Aged 7-14 Years in Diyarbakir Province
      Center.
AB  - BACKGROUND Hepatitis A virus (HAV) is a common morbidity in society, and
      mortality is more common in older ages. It is important to identify the
      prevalence in the population, the development of primary protection methods, and
      vaccination policies. This study aimed to identify anti-HAV seropositivity in
      children in 3 different schools in Diyarbakir, Turkey, to evaluate the risk
      factors influencing prevalence, and thus to develop strategies to prevent
      infection. MATERIAL AND METHODS The study was a prospective investigation of 600
      children with a mean age of 10.5 years (range, 7-14), including 291 males and 309
      females. RESULTS The seropositivity was 45.7% (41.2% in males and 49.8% females)
      with a statistically significant difference by sex (p=0.042). It was also
      significantly correlated with age. Factors significantly associated with
      seropositivity were educational level and income of parents, number of rooms in
      the house, type of toilet, number of siblings, and source of drinking water.
      Hence, older age, more siblings, crowded household, and low socioeconomic level
      are risk factors for seropositivity. CONCLUSIONS Protection strategies for the
      disease include improving socioeconomic level, increasing the level of education,
      disseminating appropriate drinking water, improving infrastructure and sewage
      disposal, and public health education on hygiene and the importance of
      vaccination. We also believe that active immunization against HAV in Turkey in
      general and in our province in particular can prevent infection in children and
      related complications in older people.

PMID- 29445080
TI  - Modeling radiation injury-induced cell death and countermeasure drug responses in
      a human Gut-on-a-Chip.
AB  - Studies on human intestinal injury induced by acute exposure to gamma-radiation
      commonly rely on use of animal models because culture systems do not faithfully
      mimic human intestinal physiology. Here we used a human Gut-on-a-Chip (Gut Chip)
      microfluidic device lined by human intestinal epithelial cells and vascular
      endothelial cells to model radiation injury and assess the efficacy of radiation
      countermeasure drugs in vitro. Exposure of the Gut Chip to gamma-radiation
      resulted in increased generation of reactive oxygen species, cytotoxicity,
      apoptosis, and DNA fragmentation, as well as villus blunting, disruption of tight
      junctions, and compromise of intestinal barrier integrity. In contrast, pre
      treatment with a potential prophylactic radiation countermeasure drug,
      dimethyloxaloylglycine (DMOG), significantly suppressed all of these injury
      responses. Thus, the human Gut Chip may serve as an in vitro platform for
      studying radiation-induced cell death and associate gastrointestinal acute
      syndrome, in addition to screening of novel radio-protective medical
      countermeasure drugs.

PMID- 29445081
TI  - Baicalin administration attenuates hyperglycemia-induced malformation of
      cardiovascular system.
AB  - In this study, the effects of Baicalin on the hyperglycemia-induced
      cardiovascular malformation during embryo development were investigated. Using
      early chick embryos, an optimal concentration of Baicalin (6 MUM) was identified
      which could prevent hyperglycemia-induced cardiovascular malformation of embryos.
      Hyperglycemia-enhanced cell apoptosis was reduced in embryos and HUVECs in the
      presence of Baicalin. Hyperglycemia-induced excessive ROS production was
      inhibited when Baicalin was administered. Analyses of SOD, GSH-Px, MQAE and GABAA
      suggested Baicalin plays an antioxidant role in chick embryos possibly through
      suppression of outwardly rectifying Cl(-) in the high-glucose microenvironment.
      In addition, hyperglycemia-enhanced autophagy fell in the presence of Baicalin,
      through affecting the ubiquitin of p62 and accelerating autophagy flux. Both
      Baicalin and Vitamin C could decrease apoptosis, but CQ did not, suggesting
      autophagy to be a protective function on the cell survival. In mice, Baicalin
      reduced the elevated blood glucose level caused by streptozotocin (STZ). Taken
      together, these data suggest that hyperglycemia-induced embryonic cardiovascular
      malformation can be attenuated by Baicalin administration through suppressing the
      excessive production of ROS and autophagy. Baicalin could be a potential
      candidate drug for women suffering from gestational diabetes mellitus.

PMID- 29445082
TI  - Pyruvate kinase M2 regulates photoreceptor structure, function, and viability.
AB  - Pyruvate kinase M2 (PKM2) is a glycolytic enzyme that is expressed in cancer
      cells. Its role in tumor metabolism is not definitively established, but
      investigators have suggested that regulation of PKM2 activity can cause
      accumulation of glycolytic intermediates and increase flux through the pentose
      phosphate pathway. Recent evidence suggests that PKM2 also may have non-metabolic
      functions, including as a transcriptional co-activator in gene regulation. We
      reported previously that PKM2 is abundant in photoreceptor cells in mouse
      retinas. In the present study, we conditionally deleted PKM2 (rod-cre PKM2-KO) in
      rod photoreceptors and found that the absence of PKM2 causes increased expression
      of PKM1 in rods. Analysis of metabolic flux from U-13C glucose shows that rod-cre
      PKM2-KO retinas accumulate glycolytic intermediates, consistent with an overall
      reduction in the amount of pyruvate kinase activity. Rod-cre PKM2-KO mice also
      have an increased NADPH availability could favor lipid synthesis, but we found no
      difference in phospholipid synthesis between rod-cre PKM2 KO and PKM2-positive
      controls. As rod-cre PKM2-KO mice aged, we observed a significant loss of rod
      function, reduced thickness of the photoreceptor outer segment layer, and reduced
      expression of photoreceptor proteins, including PDE6beta. The rod-cre PKM2-KO
      retinas showed greater TUNEL staining than wild-type retinas, indicating a slow
      retinal degeneration. In vitro analysis showed that PKM2 can regulate
      transcriptional activity from the PDE6beta promoter in vitro. Our findings
      indicate that both the metabolic and transcriptional regulatory functions of PKM2
      may contribute to photoreceptor structure, function, and viability.

PMID- 29445083
TI  - Fibroblast growth factor-21 prevents diabetic cardiomyopathy via AMPK-mediated
      antioxidation and lipid-lowering effects in the heart.
AB  - Our previous studies showed that both exogenous and endogenous FGF21 inhibited
      cardiac apoptosis at the early stage of type 1 diabetes. Whether FGF21 induces
      preventive effect on type 2 diabetes-induced cardiomyopathy was investigated in
      the present study. High-fat-diet/streptozotocin-induced type 2 diabetes was
      established in both wild-type (WT) and FGF21-knockout (FGF21-KO) mice followed by
      treating with FGF21 for 4 months. Diabetic cardiomyopathy (DCM) was diagnosed by
      significant cardiac dysfunction, remodeling, and cardiac lipid accumulation
      associated with increased apoptosis, inflammation, and oxidative stress, which
      was aggravated in FGF21-KO mice. However, the cardiac damage above was prevented
      by administration of FGF21. Further studies demonstrated that the metabolic
      regulating effect of FGF21 is not enough, contributing to FGF21-induced
      significant cardiac protection under diabetic conditions. Therefore, other
      protective mechanisms must exist. The in vivo cardiac damage was mimicked in
      primary neonatal or adult mouse cardiomyocytes treated with HG/Pal, which was
      inhibited by FGF21 treatment. Knockdown of AMPKalpha1/2, AKT2, or NRF2 with their
      siRNAs revealed that FGF21 protected cardiomyocytes from HG/Pal partially via
      upregulating AMPK-AKT2-NRF2-mediated antioxidative pathway. Additionally,
      knockdown of AMPK suppressed fatty acid beta-oxidation via inhibition of ACC-CPT
      1 pathway. And, inhibition of fatty acid beta-oxidation partially blocked FGF21
      induced protection in cardiomyocytes. Further, in vitro and in vivo studies
      indicated that FGF21-induced cardiac protection against type 2 diabetes was
      mainly attributed to lipotoxicity rather than glucose toxicity. These results
      demonstrate that FGF21 functions physiologically and pharmacologically to prevent
      type 2 diabetic lipotoxicity-induced cardiomyopathy through activation of both
      AMPK-AKT2-NRF2-mediated antioxidative pathway and AMPK-ACC-CPT-1-mediated lipid
      lowering effect in the heart.

PMID- 29445085
TI  - Glycogen synthase kinase-3beta inhibition promotes lysosome-dependent degradation
      of c-FLIPL in hepatocellular carcinoma.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is a ubiquitously expressed
      serine/threonine kinase involved in a variety of functions ranging from the
      control of glycogen metabolism to transcriptional regulation. We recently
      demonstrated that GSK-3beta inhibition triggered ASK1-JNK-dependent apoptosis in
      human hepatocellular carcinoma (HCC) cells. However, the comprehensive picture of
      downstream GSK-3beta-regulated pathways/functions remains elusive. In this study,
      we showed that GSK-3beta was aberrantly activated in HCC. Pharmacological
      inhibition and genetic depletion of GSK-3beta suppressed the growth and induced
      caspase-dependent apoptosis in HCC cells. In addition, GSK-3beta inhibition
      induced apoptosis through downregulation of c-FLIPL in HCC, which was caused by
      biogenesis of functional lysosomes and subsequently c-FLIPL translocated to
      lysosome for degradation. This induction of the lysosome-dependent c-FLIPL
      degradation was associated with nuclear translocation of transcription factor EB
      (TFEB), a master regulator of lysosomal biogenesis. Moreover, GSK-3beta
      inhibition-induced TFEB translocation acts through activation of AMPK and
      subsequently suppression of mTOR activity. Thus our findings reveal a novel
      mechanism by which inhibition of GSK-3beta promotes lysosome-dependent
      degradation of c-FLIPL. Our study shows that GSK-3beta may become a promising
      therapeutic target for HCC.

PMID- 29445084
TI  - The carnitine system and cancer metabolic plasticity.
AB  - Metabolic flexibility describes the ability of cells to respond or adapt its
      metabolism to support and enable rapid proliferation, continuous growth, and
      survival in hostile conditions. This dynamic character of the cellular metabolic
      network appears enhanced in cancer cells, in order to increase the adaptive
      phenotype and to maintain both viability and uncontrolled proliferation. Cancer
      cells can reprogram their metabolism to satisfy the energy as well as the
      biosynthetic intermediate request and to preserve their integrity from the harsh
      and hypoxic environment. Although several studies now recognize these
      reprogrammed activities as hallmarks of cancer, it remains unclear which are the
      pathways involved in regulating metabolic plasticity. Recent findings have
      suggested that carnitine system (CS) could be considered as a gridlock to finely
      trigger the metabolic flexibility of cancer cells. Indeed, the components of this
      system are involved in the bi-directional transport of acyl moieties from cytosol
      to mitochondria and vice versa, thus playing a fundamental role in tuning the
      switch between the glucose and fatty acid metabolism. Therefore, the CS
      regulation, at both enzymatic and epigenetic levels, plays a pivotal role in
      tumors, suggesting new druggable pathways for prevention and treatment of human
      cancer.

PMID- 29445086
TI  - The oncogene Etv5 promotes MET in somatic reprogramming and orchestrates
      epiblast/primitive endoderm specification during mESCs differentiation.
AB  - Unipotent spermatogonial stem cells (SSCs) can be efficiently reprogrammed into
      pluripotent stem cells only by manipulating the culture condition, without
      introducing exogenous reprogramming factors. This phenotype raises the hypothesis
      that the endogenous transcription factors (TFs) in SSCs may facilitate
      reprogramming to acquire pluripotency. In this study, we screened a pool of SSCs
      TFs (Bcl6b, Lhx1, Foxo1, Plzf, Id4, Taf4b, and Etv5), and found that oncogene
      Etv5 could dramatically increase the efficiency of induced pluripotent stem cells
      (iPSCs) generation when combined with Yamanaka factors. We also demonstrated that
      Etv5 could promote mesenchymal-epithelial transition (MET) at the early stage of
      reprogramming by regulating Tet2-miR200s-Zeb1 axis. In addition, Etv5 knockdown
      in mouse embryonic stem cells (mESCs) could decrease the genomic 5hmC level by
      downregulating Tet2. Furthermore, the embryoid body assay revealed that Etv5
      could positively regulate primitive endoderm specification through regulating
      Gata6 and negatively regulate epiblast specification by inhibiting Fgf5
      expression. In summary, our findings provide insights into understanding the
      regulation mechanisms of Etv5 under the context of somatic reprogramming, mESCs
      maintenance, and differentiation.

PMID- 29445087
TI  - Rage induces hepatocellular carcinoma proliferation and sorafenib resistance by
      modulating autophagy.
AB  - The receptor for advanced glycation end products (Rage) is involved in the
      development of various tumors and acts as an oncogenic protein. Rage is
      overexpressed in tumors including hepatocellular carcinoma (HCC). However, the
      molecular mechanism of Rage in HCC progression and sorafenib resistance remains
      unclear. In this study, enhanced Rage expression is highly associated
      proliferation and contributes to sorafenib resistance. Rage deficiency
      contributed to autophagy induction through activating AMPK/mTOR signaling
      pathway, which is important for sorafenib response. Moreover, the interactions
      between Rage and Rage ligands such as high mobility group box 1 (HMGB1) and
      s100a4 positively increased Rage expression. Our data indicate that Rage may be a
      potential target for therapeutic intervention in HCC and biomarker for sorafenib
      resistance.

PMID- 29445088
TI  - Cancer cell responses to Hsp70 inhibitor JG-98: Comparison with Hsp90 inhibitors
      and finding synergistic drug combinations.
AB  - Hsp70 is a promising anti-cancer target. Our JG-98 series of Hsp70 inhibitors
      show anti-cancer activities affecting both cancer cells and tumor-associated
      macrophages. They disrupt Hsp70 interaction with a co-chaperone Bag3 and affect
      signaling pathways important for cancer development. Due to a prior report that
      depletion of Hsp70 causes similar responses as depletion of Hsp90, interest to
      Hsp70 inhibitors as drug prototypes is hampered by potential similarity of their
      effects to effects of Hsp90 inhibitors. Here, using the Connectivity Map platform
      we demonstrate that physiological effects of JG-98 are dissimilar from effects of
      Hsp90 inhibitors, thus justifying development of these compounds. Using gene
      expression and ActivSignal IPAD platform, we identified pathways modulated by JG
      98. Some of these pathways were affected by JG-98 in Bag3-dependent (e.g. ERK)
      and some in Bag3-independent manner (e.g. Akt or c-myc), indicating multiple
      effects of Hsp70 inhibition. Further, we identified genes that modulate cellular
      responses to JG-98, developed approaches to predict potent combinations of JG-98
      with known drugs, and demonstrated that inhibitors of proteasome, RNApol, Akt and
      RTK synergize with JG-98. Overall, here we established unique effects of novel
      Hsp70 inhibitors on cancer cell physiology, and predicted potential drug
      combinations for pre-clinical development.

PMID- 29445089
TI  - MiR-27a-5p Increases Steer Fat Deposition Partly by Targeting Calcium-sensing
      Receptor (CASR).
AB  - Castration increases fat deposition, improving beef quality in cattle. Here, the
      steer group exhibited a significantly higher intramuscular fat (IMF) content than
      the bull group. To determine the potential roles of microRNAs (miRNAs) in
      castration-induced fat deposition, differential expression patterns of miRNA in
      liver tissue were investigated in bulls and steers. A total of 7,827,294 clean
      reads were obtained from the bull liver library, and 8,312,483 were obtained from
      the steer liver library; 452 conserved bovine miRNAs and 20 novel miRNAs were
      identified. The results showed that the expression profiles of miRNA in liver
      tissue were changed by castration, and 12 miRNAs that were differentially
      expressed between bulls and steers were identified. Their target genes were
      majorly involved in the metabolic, PI3K-Akt, and MAPK signaling pathways.
      Furthermore, six differentially expressed miRNAs were validated by quantitative
      real-time PCR, and luciferase reporter assays verified that calcium-sensing
      receptor (CASR) was the direct target of miR-27a-5p. Meantime, we found that the
      expression level of CASR was significantly higher in steers than in bulls, and
      revealed that CASR gene silencing in bovine hepatocytes significantly inhibited
      triacylglycerol (TAG) accumulation and reduced secretion of very low density
      lipoprotein (VLDL). These results obtained in the liver indicate that miR-27a-5p
      may increase fat deposition partly by targeting CASR in steers.

PMID- 29445090
TI  - Two Sprayer CVD Synthesis of Nitrogen-doped Carbon Sponge-type Nanomaterials.
AB  - Nitrogen-doped carbon sponge-type nanostructures (N-CSTNs) containing coaxial
      multiwalled carbon nanotubes are synthesized at 1020  degrees C by using a
      modified chemical vapor deposition (CVD) arrangement. Here, the CVD reactor is
      supplied by two flows coming from two independent sprayers (called sprayer A and
      sprayer B). The nebulized material in each sprayer is transported by two
      different gases with different flow velocities. The synthesis of carbon N-CSTNs
      is performed using different precursors: sprayer A contains a solution composed
      of ethanol, thiophene and ferrocene, whereas sprayer B contains a solution of
      benzylamine, thiophene and ferrocene. Samples are classified according to the
      position inside the reactor and characterized by scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray
      photoelectron spectroscopy (XPS), Raman spectroscopy and thermogravimetric
      analysis (TGA). Samples collected at the beginning of the reactor contain curly
      structures with diameters of 10-100 nm. At the end of the reactor, the sample is
      mainly formed by one type of structure. A spongy-type material is mainly formed
      in the hottest zone of the tubular furnace. The N-CSTNs are highly hydrophobic
      with oil sorption properties, which could be used for adsorption of oil spills.

PMID- 29445091
TI  - Thermal stabilization of the deglycating enzyme Amadoriase I by rational design.
AB  - Amadoriases are a class of FAD-dependent enzymes that are found in fungi, yeast
      and bacteria and that are able to hydrolyze glycated amino acids, cleaving the
      sugar moiety from the amino acidic portion. So far, engineered Amadoriases have
      mostly found practical application in the measurement of the concentration of
      glycated albumin in blood samples. However, these engineered forms of Amadoriases
      show relatively low absolute activity and stability levels, which affect their
      conditions of use. Therefore, enzyme stabilization is desirable prior to function
      altering molecular engineering. In this work, we describe a rational design
      strategy based on a computational screening method to evaluate a library of
      potentially stabilizing disulfide bonds. Our approach allowed the identification
      of two thermostable Amadoriase I mutants (SS03 and SS17) featuring a
      significantly higher T50 (55.3  degrees C and 60.6  degrees C, respectively)
      compared to the wild-type enzyme (52.4  degrees C). Moreover, SS17 shows clear
      hyperstabilization, with residual activity up to 95  degrees C, whereas the wild
      type enzyme is fully inactive at 55  degrees C. Our computational screening
      method can therefore be considered as a promising approach to expedite the design
      of thermostable enzymes.

PMID- 29445092
TI  - 3D Plasmon Coupling Assisted Sers on Nanoparticle-Nanocup Array Hybrids.
AB  - Unique colorimetric optical properties of nanomaterials can effectively influence
      the light absorption or emission of molecules. Here, we design plasmonic
      substrate for surface-enhanced Raman scattering (SERS) by inducing three
      dimensional (3D) hot spots on the sensing surface. The 3D hot spots are formed by
      the self-assembly of plasmonic nanoparticles (NPs) on a 3D plasmonic nanocup
      array structure. This 3D hot spot formation on the periodic nanocup arrays
      achieves much higher SERS enhancement factor than the 2D NP arrays, which have
      been conventionally sought SERS substrates. We also utilize the colorimetric
      properties of the nanocup arrays for an additional degree of SERS enhancement.
      Colorimetry, achieved by tunable plasmon resonance wavelength by controlling
      dielectric property on the nanocup array surface, eases the modulation of the
      plasmonic resonance condition without modifying the nanostructure design. By
      continuously monitoring the shifts of the plasmon resonance condition and its
      effect on the light absorption and emission of the nearby molecules, we verify
      that larger SERS enhancement is achieved when the plasmon resonance wavelength is
      matched with the Raman excitation wavelength. The ease of plasmon resonance
      tuning of this nanocup array-nanoparticle hybrid structure allows versatile SERS
      enhancement for a variety of different Raman measurement conditions.

PMID- 29445093
TI  - Hydroxynitrile lyases from cyanogenic millipedes: molecular cloning, heterologous
      expression, and whole-cell biocatalysis for the production of (R)-mandelonitrile.
AB  - Hydroxynitrile lyases (HNLs), which are key enzymes in cyanogenesis, catalyze the
      cleavage of cyanohydrins into carbonyl compounds and hydrogen cyanide. Since HNLs
      also catalyze the reverse reaction, they are used industrially for the asymmetric
      synthesis of cyanohydrins, which are valuable building blocks of pharmaceuticals
      and fine chemicals. HNLs have been isolated from cyanogenic plants and bacteria.
      Recently, an HNL from the cyanogenic millipede Chamberlinius hualienensis was
      shown to have the highest specific activity for (R)-mandelonitrile synthesis,
      along with high stability and enantioselectivity. However, no HNLs have been
      isolated from other cyanogenic millipedes. We identified and characterized HNLs
      from 10 cyanogenic millipedes in the Paradoxosomatidae and Xystodesmidae.
      Sequence analyses showed that HNLs are conserved among cyanogenic millipedes and
      likely evolved from one ancestral gene. The HNL from Parafontaria tonominea was
      expressed in Escherichia coli SHuffle T7 and showed high specific activity for
      (R)-mandelonitrile synthesis and stability at a range of pHs and temperatures.
      The stability of millipede HNLs is likely due to disulfide bond(s). The E. coli
      cells expressing HNL produced (R)-mandelonitrile with 97.6% enantiomeric excess
      without organic solvents. These results demonstrate that cyanogenic millipedes
      are a valuable source of HNLs with high specific activity and stability.

PMID- 29445094
TI  - Being slightly overweight is associated with a better quality of life in breast
      cancer survivors.
AB  - To examine the association between BMI and QOL in breast cancer survivors in
      China, we conducted a cross-sectional survey and recruited 10708 breast cancer
      survivors. Survivors self-reported QOL was measured using the EORTC QLQ-C30 and
      the QLQ-BR23. The impact of BMI on QOL was examined through standard least
      squares regression. Normal weight and overweight survivors were more likely to
      have a better QOL than underweight and obese survivors and the results were
      similar to survivors diagnosed as having chronic diseases. After adjustment for
      clinical and sociodemographic factors, the QOL increased with increasing BMI in
      breast cancer survivors ranged from underweight to overweight with no chronic
      diseases, especially in the scales of emotional function and fatigue. Obese
      breast cancer survivors reported a significantly worse QOL compared to normal
      weight and overweight breast cancer survivors. Within breast cancer survivors
      with one or more chronic diseases, it was more obvious that overweight ones had a
      significantly better QOL with clear evidence of a dose relationship across
      underweight to overweight in almost all scales. Unlike obese breast cancer
      survivors without chronic diseases, the ones with chronic disease(s) had a
      similar QOL compared to normal weight breast cancer survivors in all scales
      except in the domain of fatigue.

PMID- 29445095
TI  - Granzyme B deficiency promotes osteoblastic differentiation and calcification of
      vascular smooth muscle cells in hypoxic pulmonary hypertension.
AB  - Calcification is a major risk factor for vascular integrity. This pathological
      symptom and the underlying mechanisms in hypoxic pulmonary artery hypertension
      remain elusive. Here we report that pulmonary vascular medial calcification is
      elevated in pulmonary artery hypertension models as a result of an osteoblastic
      phenotype change of pulmonary arterial smooth muscle cells induced by hypoxia.
      Notably, inhibiting store-operated calcium channels significantly decreased
      osteoblastic differentiation and calcification of pulmonary arterial smooth
      muscle cells under hypoxia. We identified granzyme B, a major constituent of
      cytotoxic T lymphocytes/natural killer cell granules involved in apoptosis, as
      the main regulator of pulmonary arterial calcification. Overexpression of
      granzyme B blocked the mineralization through its effect on store-operated
      calcium channels in cultured pulmonary arterial smooth muscle cells under hypoxic
      conditions. Mice with overexpression of granzyme B exposed to hypoxia for 3 weeks
      showed attenuated vascular calcification and pathological progression of hypoxic
      pulmonary arterial hypertension. Our findings emphasize the central function of
      granzyme B in coordinating vascular calcification in hypoxic pulmonary arterial
      hypertension.

PMID- 29445096
TI  - Chronic intermittent hypoxia promotes myocardial ischemia-related ventricular
      arrhythmias and sudden cardiac death.
AB  - We investigated the effects of intermittent hypoxia (IH), such as that
      encountered in severe obstructive sleep apnea (OSA) patients, on the development
      and severity of myocardial ischemia-related ventricular arrhythmias. Rats were
      exposed to 14 days of IH (30 s at 5%O2 and 30 s at 21%O2, 8 h.day-1) or normoxia
      (N, similar air-air cycles) and submitted to a 30-min coronary ligature. Arterial
      blood pressure (BP) and ECG were recorded for power spectral analysis, ECG
      interval measurement and arrhythmia quantification. Left ventricular monophasic
      action potential duration (APD) and expression of L-type calcium (LTCC) and
      transient receptor potential (TRPC) channels were assessed in adjacent epicardial
      and endocardial sites. Chronic IH enhanced the incidence of ischemic arrhythmias,
      in particular ventricular fibrillation (66.7% vs. 33.3% in N rats, p < 0.05). IH
      also increased BP and plasma norepinephine levels along with increased low
      frequency (LF), decreased high-frequency (HF) and increased LF/HF ratio of heart
      rate and BP variability. IH prolonged QTc and Tpeak-to-Tend intervals, increased
      the ventricular APD gradient and upregulated endocardial but not epicardial LTCC,
      TRPC1 and TRPC6 (p < 0.05). Chronic IH, is a major risk factor for sudden cardiac
      death upon myocardial ischemia through sympathoactivation and alterations in
      ventricular repolarization, transmural APD gradient and endocardial calcium
      channel expression.

PMID- 29445097
TI  - Complete Transcriptome Profiling of Normal and Age-Related Macular Degeneration
      Eye Tissues Reveals Dysregulation of Anti-Sense Transcription.
AB  - Age-related macular degeneration (AMD) predominantly affects the retina and
      retinal pigment epithelium in the posterior eye. While there are numerous studies
      investigating the non-coding transcriptome of retina and RPE, few significant
      differences between AMD and normal tissues have been reported. Strand specific
      RNA sequencing of both peripheral retina (PR) and RPE-Choroid-Sclera (PRCS), in
      both AMD and matched normal controls were generated. The transcriptome analysis
      reveals a highly significant and consistent impact on anti-sense transcription as
      well as moderate changes in the regulation of non-coding (sense) RNA. Hundreds of
      genes that do not express anti-sense transcripts in normal PR and PRCS
      demonstrate significant anti-sense expression in AMD in all patient samples.
      Several pathways are highly enriched in the upregulated anti-sense transcripts-in
      particular the EIF2 signaling pathway. These results call for a deeper
      exploration into anti-sense and noncoding RNA regulation in AMD and their
      potential as therapeutic targets.

PMID- 29445098
TI  - Representational similarity analysis reveals task-dependent semantic influence of
      the visual word form area.
AB  - Access to semantic information of visual word forms is a key component of reading
      comprehension. In this study, we examined the involvement of the visual word form
      area (VWFA) in this process by investigating whether and how the activity
      patterns of the VWFA are influenced by semantic information during semantic
      tasks. We asked participants to perform two semantic tasks - taxonomic or
      thematic categorization - on visual words while obtaining the blood-oxygen-level
      dependent (BOLD) fMRI responses to each word. Representational similarity
      analysis with four types of semantic relations (taxonomic, thematic, subjective
      semantic rating and word2vec) revealed that neural activity patterns of the VWFA
      were associated with taxonomic information only in the taxonomic task, with
      thematic information only in the thematic task and with the composite semantic
      information measured by word2vec in both semantic tasks. Furthermore, the
      semantic information in the VWFA cannot be explained by confounding factors
      including orthographic, low-level visual and phonological information. These
      findings provide positive evidence for the presence of both orthographic and task
      relevant semantic information in the VWFA and have significant implications for
      the neurobiological basis of reading.

PMID- 29445099
TI  - Pharmacokinetic-pharmacodynamic correlations in the development of ginger extract
      as an anticancer agent.
AB  - Anticancer efficacy of ginger phenolics (GPs) has been demonstrated in various in
      vitro assays and xenograft mouse models. However, only sub-therapeutic plasma
      concentrations of GPs were detected in human and mouse pharmacokinetic (PK)
      studies. Intriguingly, a significant portion of GPs occurred as phase II
      metabolites (mainly glucuronide conjugates) in plasma. To evaluate the
      disposition of GPs and understand the real players responsible for efficacy, we
      performed a PK and tissue distribution study in mice. Plasma exposure of GPs was
      similar on day 1 and 7, suggesting no induction or inhibition of clearance
      pathways. Both free and conjugated GPs accumulated in all tissues including
      tumors. While non-cytotoxicity of 6-ginerol glucuronide precluded the role of
      conjugated GPs in cell death, the free forms were cytotoxic against prostate
      cancer cells. The efficacy of ginger was best explained by the reconversion of
      conjugated GPs to free forms by beta-glucuronidase, which is over-expressed in
      the tumor tissue. This previously unrecognized two-step process suggests an
      instantaneous conversion of ingested free GPs into conjugated forms, followed by
      their subsequent absorption into systemic circulation and reconversion into free
      forms. This proposed model uncovers the mechanistic underpinnings of ginger's
      anticancer activity despite sub-therapeutic levels of free GPs in the plasma.

PMID- 29445100
TI  - Pretreatment Inflammatory Indexes as Prognostic Predictors for Survival in
      Colorectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy.
AB  - This study was to evaluate the prognostic value of pretreatment inflammatory
      indexes including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte
      ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation
      index (SII) in colorectal cancer (CRC) patients receiving neoadjuvant
      chemoradiotherapy (CRT). We enrolled 98 eligible CRC patients and divided them
      into high or low NLR, PLR, LMR, and SII groups according to their median index
      value, respectively. Univariate and multivariate analysis were performed to
      identify the potential predictors of progression-free survival (PFS) and overall
      survival (OS). In the univariate analysis, ECOG performance status, distant
      metastasis, NLR, PLR, LMR, and SII were found to be significantly associated with
      PFS and OS. In the multivariate analysis, ECOG performance status, distant
      metastasis, and NLR were identified to be independent predictors of PFS (HR
      2.487, p = 0.012; HR 2.422, p = 0.042; HR 2.243, p = 0.034, respectively), and OS
      (HR 2.237, p = 0.018; HR 2.757, p = 0.020; HR 2.336, p = 0.017, respectively).
      The results of our study revealed that ECOG performance status, distant
      metastasis and NLR were independent prognostic factors of PFS and OS in CRC
      patients receiving neoadjuvant CRT.

PMID- 29445101
TI  - Projective measurement onto arbitrary superposition of weak coherent state bases.
AB  - One of the peculiar features in quantum mechanics is that a superposition of
      macroscopically distinct states can exist. In optical system, this is highlighted
      by a superposition of coherent states (SCS), i.e. a superposition of classical
      states. Recently this highly nontrivial quantum state and its variant have been
      demonstrated experimentally. Here we demonstrate the superposition of coherent
      states in quantum measurement which is also a key concept in quantum mechanics.
      More precisely, we propose and implement a projection measurement onto an
      arbitrary superposition of two weak coherent states in optical system. The
      measurement operators are reconstructed experimentally by a novel quantum
      detector tomography protocol. Our device is realized by combining the
      displacement operation and photon counting, well established technologies, and
      thus has implications in various optical quantum information processing
      applications.

PMID- 29445103
TI  - Mesoscopic physical removal of material using sliding nano-diamond contacts.
AB  - Wear mechanisms including fracture and plastic deformation at the nanoscale are
      central to understand sliding contacts. Recently, the combination of tip-induced
      material erosion with the sensing capability of secondary imaging modes of AFM,
      has enabled a slice-and-view tomographic technique named AFM tomography or
      Scalpel SPM. However, the elusive laws governing nanoscale wear and the large
      quantity of atoms involved in the tip-sample contact, require a dedicated
      mesoscale description to understand and model the tip-induced material removal.
      Here, we study nanosized sliding contacts made of diamond in the regime whereby
      thousands of nm3 are removed. We explore the fundamentals of high-pressure tip
      induced material removal for various materials. Changes in the load force are
      systematically combined with AFM and SEM to increase the understanding and the
      process controllability. The nonlinear variation of the removal rate with the
      load force is interpreted as a combination of two contact regimes each dominating
      in a particular force range. By using the gradual transition between the two
      regimes, (1) the experimental rate of material eroded on each tip passage is
      modeled, (2) a controllable removal rate below 5 nm/scan for all the materials is
      demonstrated, thus opening to future development of 3D tomographic AFM.

PMID- 29445102
TI  - Reversal of stress fibre formation by Nitric Oxide mediated RhoA inhibition leads
      to reduction in the height of preformed thrombi.
AB  - Evidence has emerged to suggest that thrombi are dynamic structures with distinct
      areas of differing platelet activation and inhibition. We hypothesised that
      Nitric oxide (NO), a platelet inhibitor, can modulate the actin cytoskeleton
      reversing platelet spreading, and therefore reduce the capability of thrombi to
      withstand a high shear environment. Our data demonstrates that GSNO, DEANONOate,
      and a PKG-activating cGMP analogue reversed stress fibre formation and increased
      actin nodule formation in adherent platelets. This effect is sGC dependent and
      independent of ADP and thromboxanes. Stress fibre formation is a RhoA dependent
      process and NO induced RhoA inhibition, however, it did not phosphorylate RhoA at
      ser188 in spread platelets. Interestingly NO and PGI2 synergise to reverse stress
      fibre formation at physiologically relevant concentrations. Analysis of high
      shear conditions indicated that platelets activated on fibrinogen, induced stress
      fibre formation, which was reversed by GSNO treatment. Furthermore, preformed
      thrombi on collagen post perfused with GSNO had a 30% reduction in thrombus
      height in comparison to the control. This study demonstrates that NO can reverse
      key platelet functions after their initial activation and identifies a novel
      mechanism for controlling excessive thrombosis.

PMID- 29445104
TI  - Genetic modification to induce CXCR2 overexpression in mesenchymal stem cells
      enhances treatment benefits in radiation-induced oral mucositis.
AB  - Radiation-induced oral mucositis affects patient quality of life and reduces
      tolerance to cancer therapy. Unfortunately, traditional treatments are
      insufficient for the treatment of mucositis and might elicit severe side effects.
      Due to their immunomodulatory and anti-inflammatory properties, the
      transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic
      strategy for mucositis. However, systemically infused MSCs rarely reach inflamed
      sites, impacting their clinical efficacy. Previous studies have demonstrated that
      chemokine axes play an important role in MSC targeting. By systematically
      evaluating the expression patterns of chemokines in radiation/chemical-induced
      oral mucositis, we found that CXCL2 was highly expressed, whereas cultured MSCs
      negligibly express the CXCL2 receptor CXCR2. Thus, we explored the potential
      therapeutic benefits of the transplantation of CXCR2-overexpressing MSCs
      (MSCsCXCR2) for mucositis treatment. Indeed, MSCsCXCR2 exhibited enhanced
      targeting ability to the inflamed mucosa in radiation/chemical-induced oral
      mucositis mouse models. Furthermore, we found that MSCCXCR2 transplantation
      accelerated ulcer healing by suppressing the production of pro-inflammatory
      chemokines and radiogenic reactive oxygen species (ROS). Altogether, these
      findings indicate that CXCR2 overexpression in MSCs accelerates ulcer healing,
      providing new insights into cell-based therapy for radiation/chemical-induced
      oral mucositis.

PMID- 29445105
TI  - Presence-absence of marine macrozoobenthos does not generally predict abundance
      and biomass.
AB  - Many monitoring programmes of species abundance and biomass increasingly face
      financial pressures. Occupancy is often easier and cheaper to measure than
      abundance or biomass. We, therefore, explored whether measuring occupancy is a
      viable alternative to measuring abundance and biomass. Abundance- or biomass
      occupancy relationships were studied for sixteen macrozoobenthos species
      collected across the entire Dutch Wadden Sea in eight consecutive summers.
      Because the form and strength of these relationships are scale-dependent, the
      analysis was completed at different spatiotemporal scales. Large differences in
      intercept and slope of abundance- or biomass-occupancy relationships were found.
      Abundance, not biomass, was generally positively correlated with occupancy. Only
      at the largest scale, seven species showed reasonably strong abundance-occupancy
      relationships with large coefficients of determination and small differences in
      observed and predicted values (RMSE). Otherwise, and at all the other scales,
      intraspecific abundance and biomass relationships were poor. Our results showed
      that there is no generic relationship between a species' abundance or biomass and
      its occupancy. We discuss how ecological differences between species could cause
      such large variation in these relationships. Future technologies might allow
      estimating a species' abundance or biomass directly from eDNA sampling data, but
      for now, we need to rely on traditional sampling technology.

PMID- 29445106
TI  - The High-Pressure Superconducting Phase of Arsenic.
AB  - Ab initio random structure searching (AIRSS) technique is predicted a stable
      structure of arsenic (As). We find that the body-centered tetragonal (bct)
      structure with spacegroup I41/acd to be the stable structure at high pressure.
      Our calculation suggests transition sequence from the simple cubic (sc) structure
      transforms into the host-guest (HG) structure at 41 GPa and then into the bct
      structure at 81 GPa. The bct structure has been calculated using ab initio
      lattice dynamics with finite displacement method confirm the stability at high
      pressure. The spectral function alpha2F of the bct structure is higher than those
      of the body-centered cubic (bcc) structure. It is worth noting that both bct and
      bcc structures share the remarkable similarity of structural and property. Here
      we have reported the prediction of temperature superconductivity of the bct
      structure, with a T c of 4.2 K at 150 GPa.

PMID- 29445107
TI  - Progesterone Receptor Membrane Component 1 suppresses the p53 and Wnt/beta
      catenin pathways to promote human pluripotent stem cell self-renewal.
AB  - Progesterone receptor membrane component 1 (PGRMC1) is a multifunctional heme
      binding protein involved in various diseases, including cancers and Alzheimer's
      disease. Previously, we generated two monoclonal antibodies (MAbs) 108-B6 and
      4A68 against surface molecules on human pluripotent stem cells (hPSCs). Here we
      show that PGRMC1 is the target antigen of both MAbs, and is predominantly
      expressed on hPSCs and some cancer cells. PGRMC1 is rapidly downregulated during
      early differentiation of hPSCs. Although PGRMC1 knockdown leads to a spread-out
      morphology and impaired self-renewal in hPSCs, PGRMC1 knockdown hPSCs do not show
      apoptosis and autophagy. Instead, PGRMC1 knockdown leads to differentiation of
      hPSCs into multiple lineage cells without affecting the expression of
      pluripotency markers. PGRMC1 knockdown increases cyclin D1 expression and
      decreases Plk1 expression in hPSCs. PGRMC1 knockdown also induces p53 expression
      and stability, suggesting that PGRMC1 maintains hPSC self-renewal through
      suppression of p53-dependent pathway. Analysis of signaling molecules further
      reveals that PGRMC1 knockdown promotes inhibitory phosphorylation of GSK-3beta
      and increased expression of Wnt3a and beta-catenin, which leads to activation of
      Wnt/beta-catenin signaling. The results suggest that PGRMC1 suppresses the p53
      and Wnt/beta-catenin pathways to promote self-renewal and inhibit early
      differentiation in hPSCs.

PMID- 29445108
TI  - Individual and combined effects of herbicide tribenuron-methyl and fungicide
      tebuconazole on soil earthworm Eisenia fetida.
AB  - Earthworms are soil engineers that alter the soil bio-physical properties to
      favor plant growth whereas pesticides represent a significant threat to their
      abundance and soil health. Thus, we investigated the toxic effects of tribenuron
      methyl (TBM) and tebuconazole (TEB) on the soil earthworm, Eisenia fetida. The
      TBM demonstrated low toxicity to E. fetida in the contact filter paper and
      artificial soil tests, with median lethal concentrations (LC50) of 135.6 MUg cm-2
      at 48 h and 511 mg kg-1 on day 14, respectively. Similarly, TEB also showed low
      toxicity to E. fetida in the artificial soil test with LC50 of 287 mg kg-1 on day
      14. However, TEB was highly toxic to earthworm in the contact filter paper test
      with LC50 of 5.7 MUg cm-2 at 48 h. The mixture of two pesticides had an
      antagonistic effect on the earthworm. Under 0.1 LC50 of TBM and TEB, either
      single or combined application of pesticides induced oxidative stress and
      inhibited cellulase activity in early days of the earthworm exposure. However,
      both pesticides did not damage the earthworm DNA. Our results suggest that
      pesticides can negatively affect soil earthworms and provide valuable information
      regarding the responses of soil biological engineers to the lethal agrochemicals.

PMID- 29445109
TI  - Species-specified VOC emissions derived from a gridded study in the Pearl River
      Delta, China.
AB  - This study provides a top-down approach to establish an emission inventory of
      volatile organic compounds (VOC) based on ambient measurements, by combining the
      box model and positive matrix factorization (PMF) model. Species-specified VOC
      emissions, source contributions, and spatial distributions are determined based
      on regional-scale gridded measurements between September 2008 to December 2009 in
      the Pearl River Delta (PRD), China. The most prevalent anthropogenic species in
      the PRD was toluene estimated by the box model to be annual emissions of 167.8 +/
      100.5 Gg, followed by m,p-xylene (68.0 +/- 45.0 Gg), i-pentane (49.2 +/- 40.0
      Gg), ethene (47.6 +/- 27.6 Gg), n-butane (47.5 +/- 40.7 Gg), and benzene (46.8 +/
      29.0 Gg). Alkanes such as propane, i-butane, and n-pentane were 2-8 times higher
      in box model than emission inventories (EI). Species with fewer emissions were
      highly variable between EI and box model results. Hotspots of VOC emissions were
      identified in southwestern PRD and port areas, which were not reflected by bottom
      up EI. This suggests more research is needed for VOC emissions in the EI,
      especially for fuel evaporation, industrial operations and marine vessels. The
      species-specified top-down method can help improve the quality of these emission
      inventories.

PMID- 29445110
TI  - Promising Biomarkers of Environmental Enteric Dysfunction: A Prospective Cohort
      study in Pakistani Children.
AB  - Environmental Enteric Dysfunction (EED), a syndrome characterized by chronic gut
      inflammation, contributes towards stunting and poor response to enteric vaccines
      in children in developing countries. In this study, we evaluated major putative
      biomarkers of EED using growth faltering as its clinical proxy. Newborns (n =
      380) were enrolled and followed till 18 months with monthly anthropometry.
      Biomarkers associated with gut and systemic inflammation were assessed at 6 and 9
      months. Linear mixed effects model was used to determine the associations of
      these biomarkers with growth faltering between birth and 18 months. Fecal
      myeloperoxidase (neutrophil activation marker) at 6 months [beta = -0.207, p =
      0.005], and serum GLP 2 (enterocyte proliferation marker) at 6 and 9 months [6M:
      beta = -0.271, p = 0.035; 9M: beta = -0.267, p = 0.045] were associated with
      decreasing LAZ score. Ferritin at 6 and 9 months was associated with decreasing
      LAZ score [6M: beta = -0.882, p < 0.0001; 9M: beta = -0.714, p < 0.0001] and so
      was CRP [beta = -0.451, p = 0.039] and AGP [beta = -0.443, p = 0.012] at 9
      months. Both gut specific and systemic biomarkers correlated negatively with IGF
      1, but only weakly correlated, if at all with each other. We therefore conclude
      that EED may be contributing directly towards growth faltering, and this pathway
      is not entirely through the pathway of systemic inflammation.

PMID- 29445112
TI  - Nanoanalytical electron microscopy of events predisposing to mineralisation of
      turkey tendon.
AB  - The macro- and micro-structures of mineralised tissues hierarchy are well
      described and understood. However, investigation of their nanostructure is
      limited due to the intrinsic complexity of biological systems. Preceding
      transmission electron microscopy studies investigating mineralising tissues have
      not resolved fully the initial stages of mineral nucleation and growth within the
      collagen fibrils. In this study, analytical scanning transmission electron
      microscopy and electron energy-loss spectroscopy were employed to characterise
      the morphology, crystallinity and chemistry of the mineral at different stages of
      mineralization using a turkey tendon model. In the poorly mineralised regions,
      calcium ions associated with the collagen fibrils and ellipsoidal granules and
      larger clusters composed of amorphous calcium phosphate were detected. In the
      fully mineralised regions, the mineral had transformed into crystalline apatite
      with a plate-like morphology. A change in the nitrogen K-edge was observed and
      related to modifications of the functional groups associated with the
      mineralisation process. This transformation seen in the nitrogen K-edge might be
      an important step in maturation and mineralisation of collagen and lend
      fundamental insight into how tendon mineralises.

PMID- 29445111
TI  - Fluvastatin protects cochleae from damage by high-level noise.
AB  - Exposure to noise and ototoxic drugs are responsible for much of the debilitating
      hearing loss experienced by about 350 million people worldwide. Beyond hearing
      aids and cochlear implants, there have been no other FDA approved drug
      interventions established in the clinic that would either protect or reverse the
      effects of hearing loss. Using Auditory Brainstem Responses (ABR) in a guinea pig
      model, we demonstrate that fluvastatin, an inhibitor of HMG-CoA reductase, the
      rate-limiting enzyme of the mevalonate pathway, protects against loss of cochlear
      function initiated by high intensity noise. A novel synchrotron radiation based X
      ray tomographic method that imaged soft tissues at micrometer resolution in
      unsectioned cochleae, allowed an efficient, qualitative evaluation of the three
      dimensional internal structure of the intact organ. For quantitative measures,
      plastic embedded cochleae were sectioned followed by hair cell counting.
      Protection in noise-exposed cochleae is associated with retention of inner and
      outer hair cells. This study demonstrates the potential of HMG-CoA reductase
      inhibitors, already vetted in human medicine for other purposes, to protect
      against noise induced hearing loss.

PMID- 29445113
TI  - A decade of progress in myelodysplastic syndrome with chromosome 5q deletion.
AB  - There are few instances in oncology where reciprocal clinical and laboratory
      translation studies have accelerated the understanding of disease biology and
      treatment more so than the decade following the Food and Drug Administration
      (FDA) approval of lenalidomide (RevlimidTM; Celgene Corporation, Summit, NJ, USA)
      for the treatment of patients with myelodysplastic syndrome (MDS) and chromosome
      5q deletion (del(5q)). Lenalidomide was approved by the FDA in December 2005 on
      the merits of a multicenter phase 2 study, which demonstrated sustained and
      prolonged transfusion independence in the majority of participants. Since then,
      del(5q) MDS has emerged as one of the best characterized bone marrow malignancies
      and, in particular, has raised our understanding as to how allelic
      haplodeficiency underlies both its hematological phenotype and the selective
      sensitivity to lenalidomide by virtue of synthetic lethality. Herein, we review
      the clinical and biological discoveries that have advanced our understanding of
      del(5q) MDS and its treatment since its approval by United States and European
      regulatory agencies.

PMID- 29445114
TI  - Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl
      syndrome related protein CCDC28B.
AB  - Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal
      degeneration, obesity, polydactyly, renal disease and mental retardation. CCDC28B
      is a BBS-associated protein that we have previously shown plays a role in cilia
      length regulation whereby its depletion results in shortened cilia both in cells
      and Danio rerio (zebrafish). At least part of that role is achieved by its
      interaction with the mTORC2 component SIN1, but the mechanistic details of this
      interaction and/or additional functions that CCDC28B might play in the context of
      cilia remain poorly understood. Here we uncover a novel interaction between
      CCDC28B and the kinesin 1 molecular motor that is relevant to cilia. CCDC28B
      interacts with kinesin light chain 1 (KLC1) and the heavy chain KIF5B. Notably,
      depletion of these kinesin 1 components results in abnormally elongated cilia.
      Furthermore, through genetic interaction studies we demonstrate that kinesin 1
      regulates ciliogenesis through CCDC28B. We show that kinesin 1 regulates the
      subcellular distribution of CCDC28B, unexpectedly, inhibiting its nuclear
      accumulation, and a ccdc28b mutant missing a nuclear localization motif fails to
      rescue the phenotype in zebrafish morphant embryos. Therefore, we uncover a
      previously unknown role of kinesin 1 in cilia length regulation that relies on
      the BBS related protein CCDC28B.

PMID- 29445115
TI  - The thick and thin of the central corneal thickness in glaucoma.
AB  - Central corneal thickness (CCT) is an important parameter in the assessment of
      any potential glaucoma patient. While it affects prognosis in ocular
      hypertension, its value in patients diagnosed with glaucoma is less certain.
      There are several biological factors and genetic components that may influence
      glaucoma progression, which have been associated with thinner CCT. The CCT itself
      can be affected by several factors including ethnicity, age, sex, glaucoma
      medications, genetics, and the subtype of glaucoma. Besides, there is variability
      in the measurement of CCT between difference types of devices. These factors need
      to be considered in the evaluation of glaucoma patients' CCT and its effect on
      interpretation of intraocular pressure levels and risk stratification.

PMID- 29445116
TI  - Evaluation of 3D heads-up vitrectomy: outcomes of psychometric skills testing and
      surgeon satisfaction.
AB  - OBJECTIVES: To evaluate the use of a three-dimensional heads-up microscope (3DM)
      during 25-gauge pars plana vitrectomy (PPV) compared with a traditional
      ophthalmic microscope (TM) in terms of efficacy, safety, and teaching and
      learning satisfaction. METHODS: Prospective comparative interventional study.
      Fifty eyes affected by one of the following diseases: rhegmatogenous or
      tractional retinal detachment, epiretinal membrane, full-thickness macular hole,
      vitreous hemorrhage, or dropped lens. The 50 eyes were randomly assigned to one
      of two groups: group A (25 eyes) underwent 25-gauge PPV with 3DM, and group B (25
      eyes) underwent 25-gauge PPV with TM. The main outcome measures were the duration
      of the operation, intraoperative complications, and surgeon and observer
      satisfaction. A questionnaire was used to assess surgeon satisfaction according
      to the following parameters: comfort, visibility, image quality, depth
      perception, simplicity of use, maneuverability, and teaching. A questionnaire to
      assess observer satisfaction was completed by 20 observers (surgical residents or
      ophthalmic surgeons). RESULTS: The degree of satisfaction was higher using 3DM
      for both surgeons and observers (P < 0.001). The average duration of the
      operation did not differ significantly between the two methods. No major
      complications occurred for either method. CONCLUSIONS: PPV with 3DM is more
      comfortable for the surgeon and poses no substantially greater risk of
      complications for the patient. The high-definition screen delivers excellent
      depth perception and better screen parameter control, which results in high
      quality surgical performance. 3DM surgery helps to significantly improve teaching
      and learning intra-operative surgical procedures.

PMID- 29445117
TI  - Transitional correlation between inner-membrane potential and ATP levels of
      neuronal mitochondria.
AB  - The importance of highly active mitochondria and their contribution to neuronal
      function has been of recent interest. In most cases, however, mitochondrial
      activity is estimated using measurements of mitochondrial inner membrane
      potential (IMPmito), and little is known about the dynamics of native
      mitochondrial ATP (ATPmito). This study conducted simultaneous imaging of IMPmito
      and ATPmito in neurons to explore their behaviour and their correlation during
      physiological mitochondrial/neuronal activity. We found that mitochondrial size,
      transport velocity and transport direction are not dependent on ATPmito or
      IMPmito. However, changes in ATPmito and IMPmito during mitochondrial
      fission/fusion were found; IMPmito depolarized via mitochondrial fission and
      hyperpolarized via fusion, and ATPmito levels increased after fusion. Because the
      density of mitochondria is higher in growth cones (GCs) than in axonal processes,
      integrated ATPmito signals (density * ATPmito) were higher in GCs. This
      integrated signal in GCs correlated with axonal elongation. However, while the
      averaged IMPmito was relatively hyperpolarized in GCs, there was no correlation
      between IMPmito in GCs and axonal elongation. A detailed time-course analysis
      performed to clarify the reason for these discrepancies showed that IMPmito and
      ATPmito levels did not always correlate accurately; rather, there were several
      correlation patterns that changed over time.

PMID- 29445118
TI  - N1-methylnicotinamide is a signalling molecule produced in skeletal muscle
      coordinating energy metabolism.
AB  - Obesity is a major health problem, and although caloric restriction and exercise
      are successful strategies to lose adipose tissue in obese individuals, a
      simultaneous decrease in skeletal muscle mass, negatively effects metabolism and
      muscle function. To deeper understand molecular events occurring in muscle during
      weight-loss, we measured the expressional change in human skeletal muscle
      following a combination of severe caloric restriction and exercise over 4 days in
      15 Swedish men. Key metabolic genes were regulated after the intervention,
      indicating a shift from carbohydrate to fat metabolism. Nicotinamide N
      methyltransferase (NNMT) was the most consistently upregulated gene following the
      energy-deficit exercise. Circulating levels of N1-methylnicotinamide (MNA), the
      product of NNMT activity, were doubled after the intervention. The fasting-fed
      state was an important determinant of plasma MNA levels, peaking at ~18 h of
      fasting and being lowest ~3 h after a meal. In culture, MNA was secreted by
      isolated human myotubes and stimulated lipolysis directly, with no effect on
      glucagon or insulin secretion. We propose that MNA is a novel myokine that
      enhances the utilization of energy stores in response to low muscle energy
      availability. Future research should focus on applying MNA as a biomarker to
      identify individuals with metabolic disturbances at an early stage.

PMID- 29445119
TI  - Conservation of a pH-sensitive structure in the C-terminal region of spider silk
      extends across the entire silk gene family.
AB  - Spiders produce multiple silks with different physical properties that allow them
      to occupy a diverse range of ecological niches, including the underwater
      environment. Despite this functional diversity, past molecular analyses show a
      high degree of amino acid sequence similarity between C-terminal regions of silk
      genes that appear to be independent of the physical properties of the resulting
      silks; instead, this domain is crucial to the formation of silk fibers. Here, we
      present an analysis of the C-terminal domain of all known types of spider silk
      and include silk sequences from the spider Argyroneta aquatica, which spins the
      majority of its silk underwater. Our work indicates that spiders have retained a
      highly conserved mechanism of silk assembly, despite the extraordinary
      diversification of species, silk types and applications of silk over 350 million
      years. Sequence analysis of the silk C-terminal domain across the entire gene
      family shows the conservation of two uncommon amino acids that are implicated in
      the formation of a salt bridge, a functional bond essential to protein assembly.
      This conservation extends to the novel sequences isolated from A. aquatica. This
      finding is relevant to research regarding the artificial synthesis of spider
      silk, suggesting that synthesis of all silk types will be possible using a single
      process.

PMID- 29445120
TI  - Proximity of breeding and foraging areas affects foraging effort of a
      crepuscular, insectivorous bird.
AB  - When complementary resources are required for an optimal life cycle, most animals
      need to move between different habitats. However, the level of connectivity
      between resources can vary and, hence, influence individuals' behaviour. We show
      that landscape composition and configuration affect the connectivity between
      breeding (heathlands) and foraging habitats (extensively-grazed grasslands) of
      the European Nightjar (Caprimulgus europaeus), a crepuscular insectivorous bird.
      On a daily basis, nightjars connect breeding and foraging sites by rapidly
      crossing unsuitable habitats in order to exploit a higher prey biomass in
      foraging sites. However, low availability of foraging habitat near breeding sites
      and clustered landscapes greatly increase foraging distance. Birds occupying
      these sub-optimal breeding areas compensate for longer travels by increasing
      foraging duration, and their physiology shows increased stress levels. All
      findings suggest that landscape heterogeneity can affect population dynamics of
      nightjars. Therefore, we recommend an integrated management approach for this EU
      protected bird species.

PMID- 29445121
TI  - Tomato AUXIN RESPONSE FACTOR 5 regulates fruit set and development via the
      mediation of auxin and gibberellin signaling.
AB  - Auxin response factors (ARFs) encode transcriptional factors that function in the
      regulation of plant development processes. A tomato ARF gene, SlARF5, was
      observed to be expressed at high levels in emasculated ovaries but maintained low
      expression levels in pollinated ovaries. The amiRNA SlARF5 lines exhibited ovary
      growth and formed seedless fruits following emasculation. These parthenocarpic
      fruits developed fewer locular tissues, and the fruit size and weight were
      decreased in transgenic lines compared to those of wild-type fruits. Gene
      expression analysis demonstrated that several genes involved in the auxin
      signaling pathway were downregulated, whereas some genes involved in the
      gibberellin-signaling pathway were enhanced by the decreased SlARF5 mRNA levels
      in transgenic plants, indicating that SlARF5 may play an important role in
      regulating both the auxin- and gibberellin-signaling pathways during fruit set
      and development.

PMID- 29445122
TI  - Deep phenotyping of speech and language skills in individuals with 16p11.2
      deletion.
AB  - Recurrent deletions of a ~600-kb region of 16p11.2 have been associated with a
      highly penetrant form of childhood apraxia of speech (CAS). Yet prior findings
      have been based on a small, potentially biased sample using retrospectively
      collected data. We examine the prevalence of CAS in a larger cohort of
      individuals with 16p11.2 deletion using a prospectively designed assessment
      battery. The broader speech and language phenotype associated with carrying this
      deletion was also examined. 55 participants with 16p11.2 deletion (47 children, 8
      adults) underwent deep phenotyping to test for the presence of CAS and other
      speech and language diagnoses. Standardized tests of oral motor functioning,
      speech production, language, and non-verbal IQ were conducted. The majority of
      children (77%) and half of adults (50%) met criteria for CAS. Other speech
      outcomes were observed including articulation or phonological errors (i.e.,
      phonetic and cognitive-linguistic errors, respectively), dysarthria (i.e.,
      neuromuscular speech disorder), minimal verbal output, and even typical speech in
      some. Receptive and expressive language impairment was present in 73% and 70% of
      children, respectively. Co-occurring neurodevelopmental conditions (e.g., autism)
      and non-verbal IQ did not correlate with the presence of CAS. Findings indicate
      that CAS is highly prevalent in children with 16p11.2 deletion with symptoms
      persisting into adulthood for many. Yet CAS occurs in the context of a broader
      speech and language profile and other neurobehavioral deficits. Further research
      will elucidate specific genetic and neural pathways leading to speech and
      language deficits in individuals with 16p11.2 deletions, resulting in more
      targeted speech therapies addressing etiological pathways.

PMID- 29445123
TI  - Psychosocial risk predicts high readmission rates for hematopoietic cell
      transplant recipients.
AB  - Hematopoietic cell transplantation (HCT) is an intensive treatment resulting in
      disease control however subsequent psychosocial distress is common. Screening for
      psychosocial risk factors that contribute to morbidity is underutilized;
      moreover, the value in screening is uncertain. We performed a retrospective study
      of 395 HCT patients who were screened for psychosocial risk using the Transplant
      Evaluation Rating Scale (TERS). Patients were classified by psychosocial risk as
      no-risk (TERS = 26.5, 52%) vs. at-risk (TERS > 26.5, 48%), with at-risk patients
      stratified by cumulative deficits into mild risk (TERS = 27-35.5, 39%) and
      moderate risk (TERS > 35.5, 9%). At-risk patients were more likely to be
      readmitted within 90 days (mild risk HR = 1.62, p = 0.02; moderate risk HR =
      2.50, p = 0.002). Prior psychiatric history (HR = 1.81, p = 0.002) and poor
      coping skills (HR = 1.64, p = 0.04) also influenced readmission. At-risk patients
      were more likely to be readmitted for infection (no-risk = 12% vs. at-risk = 25%,
      p = 0.002). Pre-HCT screening with the TERS did not predict survival or length of
      stay although at-risk patients are at a heighted risk of readmission.
      Implementing strategies to reduce readmission in higher risk patients is
      warranted.

PMID- 29445124
TI  - Efficacy of mucosal polyanhydride nanovaccine against respiratory syncytial virus
      infection in the neonatal calf.
AB  - Human respiratory syncytial virus (HRSV) is a leading cause of severe acute lower
      respiratory tract infection in infants and children worldwide. Bovine RSV (BRSV)
      is closely related to HRSV and a significant cause of morbidity in young cattle.
      BRSV infection in calves displays many similarities to RSV infection in humans,
      including similar age dependency and disease pathogenesis. Polyanhydride
      nanoparticle-based vaccines (i.e., nanovaccines) have shown promise as adjuvants
      and vaccine delivery vehicles due to their ability to promote enhanced
      immunogenicity through the route of administration, provide sustained antigen
      exposure, and induce both antibody- and cell-mediated immunity. Here, we
      developed a novel, mucosal nanovaccine that encapsulates the post-fusion F and G
      glycoproteins from BRSV into polyanhydride nanoparticles and determined the
      efficacy of the vaccine against RSV infection using a neonatal calf model. Calves
      receiving the BRSV-F/G nanovaccine exhibited reduced pathology in the lungs,
      reduced viral burden, and decreased virus shedding compared to unvaccinated
      control calves, which correlated with BRSV-specific immune responses in the
      respiratory tract and peripheral blood. Our results indicate that the BRSV-F/G
      nanovaccine is highly immunogenic and, with optimization, has the potential to
      significantly reduce the disease burden associated with RSV infection in both
      humans and animals.

PMID- 29445125
TI  - Pin1 impairs microRNA biogenesis by mediating conformation change of XPO5 in
      hepatocellular carcinoma.
AB  - MicroRNA (miRNA) dysregulation is associated with the tumorigenesis and
      development of numerous human cancers. The defect in miRNA biogenesis is the main
      cause of miRNA dysregulation. We previously demonstrated that ERK-induced
      phosphorylation of XPO5 followed by peptidyl-prolyl cis/trans isomerase Pin1
      mediated isomerization downregulates miRNA expression and contributes to
      hepatocellular carcinoma (HCC) development. However, how Pin1 precisely regulates
      miRNA biogenesis in HCC remains elusive. Here we reveal that Pin1 has a pivotal
      role in the miRNA maturation process by modulating phosphorylated Serine-Proline
      (pS-P) motif of XPO5 in a phosphorylation-dependent manner. By recognizing and
      binding to XPO5 via its WW domain, Pin1 catalyzes the conformation change of XPO5
      and diminishes XPO5 ability to export pre-miRNAs from the nucleus to the
      cytoplasm, resulting in the reduced mature miRNA levels and promoted HCC
      development. Furthermore, downregulation of Pin1 by shRNA restores XPO5-dependent
      pre-miRNA export and effective biogenesis of mature miRNAs, leading to both in
      vitro and in vivo HCC inhibition. Therefore, our research discloses a new
      posttranscriptional regulatory mechanism of miRNA biosynthesis and provides the
      experimental basis for a novel HCC therapy by targeting Pin1.

PMID- 29445126
TI  - EGFR controls bone development by negatively regulating mTOR-signaling during
      osteoblast differentiation.
AB  - Mice deficient in epidermal growth factor receptor (Egfr-/- mice) are growth
      retarded and exhibit severe bone defects that are poorly understood. Here we show
      that EGFR-deficient mice are osteopenic and display impaired endochondral and
      intramembranous ossification resulting in irregular mineralization of their
      bones. This phenotype is recapitulated in mice lacking EGFR exclusively in
      osteoblasts, but not in mice lacking EGFR in osteoclasts indicating that
      osteoblasts are responsible for the bone phenotype. Experiments are presented
      demonstrating that signaling via EGFR stimulates osteoblast proliferation and
      inhibits their differentiation by suppression of the IGF-1R/mTOR-pathway via
      ERK1/2-dependent up-regulation of IGFBP-3. Osteoblasts from Egfr-/- mice show
      increased levels of IGF-1R and hyperactivation of mTOR-pathway proteins,
      including enhanced phosphorylation of 4E-BP1 and S6. The same changes are also
      seen in Egfr-/- bones. Importantly, pharmacological inhibition of mTOR with
      rapamycin decreases osteoblasts differentiation as well as rescues the low bone
      mass phenotype of Egfr-/- fetuses. Our results demonstrate that suppression of
      the IGF-1R/mTOR-pathway by EGFR/ERK/IGFBP-3 signaling is necessary for balanced
      osteoblast maturation providing a mechanism for the skeletal phenotype observed
      in EGFR-deficient mice.

PMID- 29445127
TI  - Cripto-1 contributes to stemness in hepatocellular carcinoma by stabilizing
      Dishevelled-3 and activating Wnt/beta-catenin pathway.
AB  - Identification and characterization of functional molecular targets conferring
      stemness properties in hepatocellular carcinoma (HCC) offers crucial insights to
      overcome the major hurdles of tumor recurrence, metastasis and chemoresistance in
      clinical management. In the current study, we investigated the significance of
      Cripto-1 in contributing to HCC stemness. Cripto-1 was upregulated in the
      sorafenib-resistant clones derived from HCC cell lines and patient-derived
      xenograft that we previously developed, suggesting an association between Cripto
      1 and stemness. By in vitro experiments, Cripto-1 fostered cell proliferation,
      migration, and invasion. It also enhanced self-renewal ability and conferred
      chemoresistance of HCC cells. Consistently, silencing of Cripto-1 suppressed in
      vivo tumorigenicity on serial transplantation. On the downstream signaling
      mechanism, expression of major components of Wnt/beta-catenin pathway beta
      catenin, AXIN2, and C-MYC, accompanied by beta-catenin activity was reduced upon
      Cripto-1 knockdown. The suppressive effects on stemness properties with Cripto-1
      knockdown in vitro and in vivo were partially rescued by forced expression of
      constitutively active beta-catenin. Further elucidation revealed the binding of
      Cripto-1 to Frizzled-7 (FZD7), low-density lipoprotein receptor-related protein 6
      (LRP6) and Dishevelled-3 (DVL3) of the Wnt/beta-catenin pathway and stabilized
      DVL3 protein. Analyses with clinical samples validated Cripto-1 overexpression in
      HCC tissues, as well as a positive correlation between Cripto-1 and AXIN2
      expressions. High Cripto-1 level in tumor was associated with poorer disease-free
      survival of HCC patients. Taken together, Cripto-1 binds to FZD7/LRP6 and DVL3,
      stabilizes DVL3 expression and activates the Wnt/beta-catenin signaling cascade
      to confer stemness in HCC. Our study findings substantiated the role of Cripto-1
      in determining stemness phenotypes of HCC and mechanistically in modulating the
      Wnt/beta-catenin signaling cascade, one of the most frequently deregulated
      pathways in liver cancer.

PMID- 29445128
TI  - The brace helices of MLKL mediate interdomain communication and oligomerisation
      to regulate cell death by necroptosis.
AB  - The programmed cell death pathway, necroptosis, relies on the pseudokinase, Mixed
      Lineage Kinase domain-Like (MLKL), for cellular execution downstream of death
      receptor or Toll-like receptor ligation. Receptor-interacting protein kinase-3
      (RIPK3)-mediated phosphorylation of MLKL's pseudokinase domain leads to MLKL
      switching from an inert to activated state, where exposure of the N-terminal four
      helix bundle (4HB) 'executioner' domain leads to cell death. The precise
      molecular details of MLKL activation, including the stoichiometry of oligomer
      assemblies, mechanisms of membrane translocation and permeabilisation, remain a
      matter of debate. Here, we dissect the function of the two 'brace' helices that
      connect the 4HB to the pseudokinase domain of MLKL. In addition to establishing
      that the integrity of the second brace helix is crucial for the assembly of mouse
      MLKL homotrimers and cell death, we implicate the brace helices as a device to
      communicate pseudokinase domain phosphorylation event(s) to the N-terminal
      executioner 4HB domain. Using mouse:human MLKL chimeras, we defined the first
      brace helix and adjacent loop as key elements of the molecular switch mechanism
      that relay pseudokinase domain phosphorylation to the activation of the 4HB
      domain killing activity. In addition, our chimera data revealed the importance of
      the pseudokinase domain in conferring host specificity on MLKL killing function,
      where fusion of the mouse pseudokinase domain converted the human 4HB + brace
      from inactive to a constitutive killer of mouse fibroblasts. These findings
      illustrate that the brace helices play an active role in MLKL regulation, rather
      than simply acting as a tether between the 4HB and pseudokinase domains.

PMID- 29445129
TI  - Light and temperature control the seasonal distribution of thaumarchaeota in the
      South Atlantic bight.
AB  - Mid-summer peaks in the abundance of Thaumarchaeota and nitrite concentration
      observed on the Georgia, USA, coast could result from in situ activity or
      advection of populations from another source. We collected data on the
      distribution of Thaumarchaeota, ammonia-oxidizing betaproteobacteria (AOB),
      Nitrospina, environmental variables and rates of ammonia oxidation during six
      cruises in the South Atlantic Bight (SAB) from April to November 2014. These data
      were used to examine seasonality of nitrification in offshore waters and to test
      the hypothesis that the bloom was localized to inshore waters. The abundance of
      Thaumarchaeota marker genes (16S rRNA and amoA) increased at inshore and
      nearshore stations starting in July and peaked in August at >107 copies L-1. The
      bloom did not extend onto the mid-shelf, where Thaumarchaeota genes ranged from
      103 to 105 copies L-1. Ammonia oxidation rates (AO) were highest at inshore
      stations during summer (to 840 nmol L-1 d-1) and were always at the limit of
      detection at mid-shelf stations. Nitrite concentrations were correlated with AO
      (R = 0.94) and were never elevated at mid-shelf stations. Gene sequences from
      samples collected at mid-shelf stations generated using Archaea 16S rRNA primers
      were dominated by Euryarchaeota; sequences from inshore and nearshore stations
      were dominated by Thaumarchaeota. Thaumarchaeota were also abundant at depth at
      the shelf-break; however, this population was phylogenetically distinct from the
      inshore/nearshore population. Our analysis shows that the bloom is confined to
      inshore waters during summer and suggests that Thaumarchaeota distributions in
      the SAB are controlled primarily by photoinhibition and secondarily by water
      temperature.

PMID- 29445130
TI  - Comparative genomic inference suggests mixotrophic lifestyle for Thorarchaeota.
AB  - Thorarchaeota are a new archaeal phylum within the Asgard superphylum, whose
      ancestors have been proposed to play possible ecological roles in cellular
      evolution. However, little is known about the lifestyles of these uncultured
      archaea. To provide a better resolution of the ecological roles and metabolic
      capacity of Thorarchaeota, we obtained Thorarchaeota genomes reconstructed from
      metagenomes of different depth layers in mangrove and mudflat sediments. These
      genomes from deep anoxic layers suggest the presence of Thorarchaeota with the
      potential to degrade organic matter, fix inorganic carbon, reduce sulfur/sulfate
      and produce acetate. In particular, Thorarchaeota may be involved in ethanol
      production, nitrogen fixation, nitrite reduction, and arsenic detoxification.
      Interestingly, these Thorarchaeotal genomes are inferred to contain the
      tetrahydromethanopterin and tetrahydrofolate Wood-Ljungdahl (WL) pathways for CO2
      reduction, and the latter WL pathway appears to have originated from bacteria.
      These archaea are predicted to be able to use various inorganic and organic
      carbon sources, possessing genes inferred to encode ribulose bisphosphate
      carboxylase-like proteins (normally without RuBisCO activity) and a near-complete
      Calvin-Benson-Bassham cycle. The existence of eukaryotic selenocysteine insertion
      sequences and many genes for proteins previously considered eukaryote-specific in
      Thorarchaeota genomes provide new insights into their evolutionary roles in the
      origin of eukaryotic cellular complexity. Resolving the metabolic capacities of
      these enigmatic archaea and their origins will enhance our understanding of the
      origins of eukaryotes and their roles in ecosystems.

PMID- 29445131
TI  - Strains of the toxic and bloom-forming Nodularia spumigena (cyanobacteria) can
      degrade methylphosphonate and release methane.
AB  - Nodularia spumigena is a nitrogen-fixing cyanobacterium that forms toxic blooms
      in the Baltic Sea each summer and the availability of phosphorous is an important
      factor limiting the formation of these blooms. Bioinformatic analysis identified
      a phosphonate degrading (phn) gene cluster in the genome of N. spumigena
      suggesting that this bacterium may use phosphonates as a phosphorus source. Our
      results show that strains of N. spumigena could grow in medium containing
      methylphosphonic acid (MPn) as the sole source of phosphorous and released
      methane when growing in medium containing MPn. We analyzed the total
      transcriptomes of N. spumigena UHCC 0039 grown using MPn and compared them with
      cultures growing in Pi-replete medium. The phnJ, phosphonate lyase gene, was
      upregulated when MPn was the sole source of phosphorus, suggesting that the
      expression of this gene could be used to indicate the presence of bioavailable
      phosphonates. Otherwise, growth on MPn resulted in only a minor reconstruction of
      the transcriptome and enabled good growth. However, N. spumigena strains were not
      able to utilize any of the anthropogenic phosphonates tested. The phosphonate
      utilizing pathway may offer N. spumigena a competitive advantage in the Pi
      limited cyanobacterial blooms of the Baltic Sea.

PMID- 29445132
TI  - Microbiome assembly of avian eggshells and their potential as transgenerational
      carriers of maternal microbiota.
AB  - The microbiome is essential for development, health and homeostasis throughout an
      animal's life. Yet, the origins and transmission processes governing animal
      microbiomes remain elusive for non-human vertebrates, oviparous vertebrates in
      particular. Eggs may function as transgenerational carriers of the maternal
      microbiome, warranting characterisation of egg microbiome assembly. Here, we
      investigated maternal and environmental contributions to avian eggshell
      microbiota in wild passerine birds: woodlark Lullula arborea and skylark Alauda
      arvensis. Using 16S rRNA gene sequencing, we demonstrated in both lark species,
      at the population and within-nest levels, that bacterial communities of freshly
      laid eggs were distinct from the female cloacal microbiome. Instead, soil-borne
      bacteria appeared to thrive on freshly laid eggs, and eggshell microbiota
      composition strongly resembled maternal skin, body feather and nest material
      communities, sources in direct contact with laid eggs. Finally, phylogenetic
      structure analysis and microbial source tracking underscored species sorting from
      directly contacting sources rather than in vivo-transferred symbionts. The female
      egg-nest system allowed an integrative assessment of avian egg microbiome
      assembly, revealing mixed modes of symbiont acquisition not previously documented
      for vertebrate eggs. Our findings illuminated egg microbiome origins, which
      suggested a limited potential of eggshells for transgenerational transmission,
      encouraging further investigation of eggshell microbiome functions in
      vertebrates.

PMID- 29445133
TI  - Photoautotrophic organisms control microbial abundance, diversity, and physiology
      in different types of biological soil crusts.
AB  - Biological soil crusts (biocrusts) cover about 12% of the Earth's land masses,
      thereby providing ecosystem services and affecting biogeochemical fluxes on a
      global scale. They comprise photoautotrophic cyanobacteria, algae, lichens and
      mosses, which grow together with heterotrophic microorganisms, forming a model
      system to study facilitative interactions and assembly principles in natural
      communities. Biocrusts can be classified into cyanobacteria-, lichen-, and
      bryophyte-dominated types, which reflect stages of ecological succession. In this
      study, we examined whether these categories include a shift in heterotrophic
      communities and whether this may be linked to altered physiological properties.
      We analyzed the microbial community composition by means of qPCR and high
      throughput amplicon sequencing and utilized flux measurements to investigate
      their physiological properties. Our results revealed that once 16S and 18S rRNA
      gene copy numbers increase, fungi become more predominant and alpha diversity
      increases with progressing succession. Bacterial communities differed
      significantly between biocrust types with a shift from more generalized to
      specialized organisms along succession. CO2 gas exchange measurements revealed
      large respiration rates of late successional crusts being significantly higher
      than those of initial biocrusts, and different successional stages showed
      distinct NO and HONO emission patterns. Thus, our study suggests that the
      photoautotrophic organisms facilitate specific microbial communities, which
      themselves strongly influence the overall physiological properties of biocrusts
      and hence local to global nutrient cycles.

PMID- 29445134
TI  - The long non-coding RNA FOXD2-AS1 promotes bladder cancer progression and
      recurrence through a positive feedback loop with Akt and E2F1.
AB  - Long non-coding RNAs (lncRNAs) have been identified as significant regulators in
      cancer progression. Positive feedback loops between lncRNAs and transcription
      factors have attracted increasing attention. Akt pathway plays a crucial role in
      bladder cancer growth and recurrence. In the present study, we demonstrate a
      novel regulatory pattern involving FOXD2-AS1, Akt, and E2F1. FOXD2-AS1 is highly
      expressed in bladder cancer and is associated with tumor stage, recurrence, and
      poor prognosis. Further experiments showed that FOXD2-AS1 promotes bladder cancer
      cell proliferation, migration, and invasion in vitro and in vivo. Microarray
      analysis demonstrated that FOXD2-AS1 negatively regulates the expression of
      Tribbles pseudokinase 3 (TRIB3), a negative regulator of Akt. Mechanistically,
      FOXD2-AS1 forms an RNA-DNA complex with the promoter of TRIB3, the
      transcriptional activity of which is subsequently repressed, and leads to the
      activation of Akt, which further increases the expression of E2F1, a vital
      transcription factor involved in the G/S transition. Interestingly, E2F1 could
      bind to the FOXD2-AS1 promoter region and subsequently enhance its
      transcriptional activity, indicating that FOXD2-AS1/Akt/E2F1 forms a feedback
      loop. In summary, this regulatory pattern of positive feedback may be a novel
      target for the treatment of bladder cancer and FOXD2-AS1 has the potential to be
      a new recurrence predictor.

PMID- 29445135
TI  - Alteration in nerves and neurotransmitter stimulation of lacrimal gland secretion
      in the TSP-1-/- mouse model of aqueous deficiency dry eye.
AB  - The purpose of this study is to determine neural, vascular, protein secretion,
      and cellular signaling changes with disease progression in lacrimal glands of the
      thrombospondin-1-/- (TSP-1-/-) mouse model of dry eye compared to C57BL/6 wild
      type (WT) mice. Neural innervation was reduced in TSP-1-/- lacrimal glands
      compared to WT controls, whereas the number of blood vessels was increased.
      Intracellular Ca2+ stores and the amount of lysosomes, mitochondria, and
      secretory granules, but not the endoplasmic reticulum, were reduced in TSP-1-/-
      compared to WT acini at 12 weeks of age. Ex vivo high KCl-evoked secretion was
      decreased in TSP-1-/- compared to WT lacrimal gland tissue pieces. The alpha1D
      adrenergic agonist-stimulated response was increased in TSP-1-/- at 4 and 24
      weeks but decreased at 12 weeks, and the ATP and MeSATP-stimulated peak [Ca2+]i
      responses were decreased at 24 weeks. These changes were observed prior to the
      appearance of mononuclear infiltrates. We conclude that in the lacrimal gland the
      absence of TSP-1: injures peripheral nerves; blocks efferent nerve activation;
      decreases protein secretion; and alters intracellular Ca2+ stores. Through these
      effects the absence of TSP-1 leads to disruption of ocular surface homeostasis
      and development of dry eye.

PMID- 29445136
TI  - Goblet cell associated antigen passages are inhibited during Salmonella
      typhimurium infection to prevent pathogen dissemination and limit responses to
      dietary antigens.
AB  - Dietary antigen acquisition by lamina propria (LP) dendritic cells (DCs) is
      crucial to induce oral tolerance and maintain homeostasis. However, encountering
      innocuous antigens during infection can lead to inflammatory responses,
      suggesting processes may limit steady-state luminal antigen capture during
      infection. We observed that goblet cell (GC) associated antigen passages (GAPs),
      a steady-state pathway delivering luminal antigens to LP-DCs, are inhibited
      during Salmonella infection. GAP inhibition was mediated by IL-1beta. Infection
      abrogated luminal antigen delivery and antigen-specific T cell proliferation in
      the mesenteric lymph node (MLN). Antigen-specific T cell proliferation to dietary
      antigen was restored by overriding GAP suppression; however, this did not restore
      regulatory T cell induction, but induced inflammatory T cell responses.
      Salmonella translocation to the MLN required GCs and correlated with GAPs.
      Genetic manipulations overriding GAP suppression, or antibiotics inducing colonic
      GAPs, but not antibiotics that do not, increased dissemination and worsened
      outcomes independent of luminal pathogen burden. Thus, steady-state sampling
      pathways are suppressed during infection to prevent responses to dietary
      antigens, limit pathogen entry, and lessen the disease. Moreover, antibiotics may
      worsen Salmonella infection by means beyond blunting gut microbiota colonization
      resistance, providing new insight into how precedent antibiotic use aggravates
      enteric infection.

PMID- 29445137
TI  - Metabolic features of cancer stem cells: the emerging role of lipid metabolism.
AB  - Cancer stem cells (CSCs) are an uncommon subset of tumor cells capable of self
      renewal, differentiating, and recreating the parental tumor when transplanted
      into the murine background. Over the past two decades, efforts toward
      understanding CSC biology culminated into identifying a set of signaling pathways
      sustaining "stemness". Nevertheless, while metabolic rewiring is nowadays
      considered a hallmark of cancer, no consensus has been reached on the metabolic
      features underlying the plastic nature of CSCs, which are capable of residing in
      a dormant state, and able to rapidly proliferate when the need to repopulate the
      tumor mass arises. An emerging concept in the field of CSC metabolism is that
      these cells are extremely reliant on the activity of enzymes involved in lipid
      metabolism, such as stearoyl-CoA desaturase 1 (SCD1) and 3-hydroxy-3
      methylglutharyl-coenzyme A reductase (HMG-CoAR). Indeed, SCD1 and HMG-CoAR have
      been described as key factors for the correct function of a number of
      concatenated pathways involved in CSC fate decision, such as Hippo and Wnt. In
      the present review, we describe metabolic futures of CSCs with a special focus on
      lipid metabolism, which until now represents an underappreciated force in
      maintaining CSCs and an attractive therapeutic target.

PMID- 29445138
TI  - Non-toxic engineered carbon nanodiamond concentrations induce
      oxidative/nitrosative stress, imbalance of energy metabolism, and mitochondrial
      dysfunction in microglial and alveolar basal epithelial cells.
AB  - Engineered nanoparticles are finding a wide spectrum of biomedical applications,
      including drug delivery and capacity to trigger cytotoxic phenomena, potentially
      useful against tumor cells. The full understanding of their biosafety and
      interactions with cell processes is mandatory. Using microglial (BV-2) and
      alveolar basal epithelial (A549) cells, in this study we determined the effects
      of engineered carbon nanodiamonds (ECNs) on cell viability, nitric oxide (NO) and
      reactive oxygen species (ROS) production, as well as on energy metabolism.
      Particularly, we initially measured decrease in cell viability as a function of
      increasing ECNs doses, finding similar cytotoxic ECN effects in the two cell
      lines. Subsequently, using apparently non-cytotoxic ECN concentrations (2 ug/mL
      causing decrease in cell number < 5%) we determined NO and ROS production, and
      measured the concentrations of compounds related to energy metabolism,
      mitochondrial functions, oxido-reductive reactions, and antioxidant defences. We
      found that in both cell lines non-cytotoxic ECN concentrations increased NO and
      ROS production with sustained oxidative/nitrosative stress, and caused energy
      metabolism imbalance (decrease in high energy phosphates and nicotinic coenzymes)
      and mitochondrial malfunctioning (decrease in ATP/ADP ratio).These results
      underline the importance to deeply investigate the molecular and biochemical
      changes occurring upon the interaction of ECNs (and nanoparticles in general)
      with living cells, even at apparently non-toxic concentration. Since the use of
      ECNs in biomedical field is attracting increasing attention the complete
      evaluation of their biosafety, toxicity and/or possible side effects both in
      vitro and in vivo is mandatory before these highly promising tools might find the
      correct application.

PMID- 29445140
TI  - Addendum: Shear-induced Notch-Cx37-p27 axis arrests endothelial cell cycle to
      enable arterial specification.

PMID- 29445139
TI  - Dynamic network biomarker indicates pulmonary metastasis at the tipping point of
      hepatocellular carcinoma.
AB  - Developing predictive biomarkers that can detect the tipping point before
      metastasis of hepatocellular carcinoma (HCC), is critical to prevent further
      irreversible deterioration. To discover such early-warning signals or biomarkers
      of pulmonary metastasis in HCC, we analyse time-series gene expression data in
      spontaneous pulmonary metastasis mice HCCLM3-RFP model with our dynamic network
      biomarker (DNB) method, and identify CALML3 as a core DNB member. All
      experimental results of gain-of-function and loss-of-function studies show that
      CALML3 could indicate metastasis initiation and act as a suppressor of
      metastasis. We also reveal the biological role of CALML3 in metastasis initiation
      at a network level, including proximal regulation and cascading influences in
      dysfunctional pathways. Our further experiments and clinical samples show that
      DNB with CALML3 reduced pulmonary metastasis in liver cancer. Actually, loss of
      CALML3 predicts shorter overall and relapse-free survival in postoperative HCC
      patients, thus providing a prognostic biomarker and therapy target in HCC.

PMID- 29445141
TI  - Continuous depth profile of the rock strength in the Nankai accretionary prism
      based on drilling performance parameters.
AB  - A new method for evaluating the in situ rock strength beneath the seafloor is
      proposed and applied to the Nankai Trough accretionary prism. The depth
      continuous in situ rock strength is a critical parameter for numerous studies in
      earth science, particularly for seismology and tectonics at plate convergence
      zones; yet, measurements are limited owing to a lack of drilled cores. Here, we
      propose a new indicator of strength, the equivalent strength (EST), which is
      determined only by drilling performance parameters such as drill string
      rotational torque, bit depth, and string rotational speed. A continuous depth
      profile of EST was drawn from 0 to 3000 m below the seafloor (mbsf) across the
      forearc basin and accretionary prism in the Nankai Trough. The EST did not show a
      significant increase around the forearc basin-accretionary prism boundary, but it
      did show a clear increase within the prism, ca. below 1500 mbsf. This result may
      indicate that even the shallow accretionary prism has been strengthened by
      horizontal compression derived from plate subduction. The EST is a potential
      parameter to continuously evaluate the in situ rock strength during drilling, and
      its accuracy of the absolute value can be improved by combining with laboratory
      drilling experiments.

PMID- 29445142
TI  - Heterogeneity and cell fate flux in single human pancreatic islet cells.

PMID- 29445143
TI  - Dry habitats sustain high CO2 emissions from temporary ponds across seasons.
AB  - Despite the increasing understanding of the magnitude and drivers of carbon gas
      emissions from inland waters, the relevance of water fluctuation and associated
      drying on their dynamics is rarely addressed. Here, we quantified CO2 and CH4
      fluxes from a set of temporary ponds across seasons. The ponds were in all
      occasion net CO2 emitters irrespective of the presence or absence of water. While
      the CO2 fluxes were in the upper range of emissions for freshwater lentic
      systems, CH4 fluxes were mostly undetectable. Dry habitats substantially
      contributed to these emissions and were always a source of CO2, whereas inundated
      habitats acted either as a source or a sink of atmospheric CO2 along the year.
      Higher concentrations of coloured and humic organic matter in water and sediment
      were linked to higher CO2 emissions. Composition of the sediment microbial
      community was related both to dissolved organic matter concentration and
      composition, but we did not find a direct link with CO2 fluxes. The presence of
      methanogenic archaea in most ponds suggested the potential for episodic CH4
      production and emission. Our results highlight the need for spatially and
      temporally inclusive approaches that consider the dry phases and habitats to
      characterize carbon cycling in temporary systems.

PMID- 29445144
TI  - Lenalidomide regulates CNS autoimmunity by promoting M2 macrophages polarization.
AB  - Multiple sclerosis (MS) is a chronic and debilitating neurological disorder of
      the central nervous system (CNS), characterized by infiltration of leukocytes
      into CNS and subsequent demyelination. Emerging evidences have revealed the
      beneficial roles of M2 macrophages in ameliorating experimental autoimmune
      encephalomyelitis (EAE), a model for MS. Here, we identify that lenalidomide
      alone could promote macrophages M2 polarization to prevent the progression of
      EAE, which is associated with subsequent inhibition of proinflammatory Th1 and
      Th17 cells both in peripheral lymph system and CNS. Depletion of macrophages by
      pharmacology treatment of clodronate liposomes or transferring lenalidomide
      induced BMDMs in EAE mice completely abolished the therapeutic effect of
      lenalidomide or prevented EAE development, respectively. The macrophages-derived
      IL10 was upregulated both in vivo and in vitro after lenalidomide treatment.
      Moreover, lenalidomide-treated IL10-dificient EAE mice had higher clinical scores
      and more severe CNS damage, and intravenous injection of lenalidomide-treated
      IL10-/- BMDMs into mice with EAE at disease onset did not reverse disease
      severity, implying IL10 may be essential in lenalidomide-ameliorated EAE.
      Mechanistically, lenalidomide significantly increased expression and autocrine
      secretion of IL10, subsequently activated STAT3-mediated expression of Ym1. These
      studies facilitate the development of potential novel therapeutic application of
      lenalidomide for the treatment of MS.

PMID- 29445145
TI  - Canagliflozin mediated dual inhibition of mitochondrial glutamate dehydrogenase
      and complex I: an off-target adverse effect.
AB  - Recent FDA Drug Safety Communications report an increased risk for acute kidney
      injury in patients treated with the gliflozin class of sodium/glucose co
      transport inhibitors indicated for treatment of type 2 diabetes mellitus. To
      identify a potential rationale for the latter, we used an in vitro human renal
      proximal tubule epithelial cell model system (RPTEC/TERT1), physiologically
      representing human renal proximal tubule function. A targeted metabolomics
      approach, contrasting gliflozins to inhibitors of central carbon metabolism and
      mitochondrial function, revealed a double mode of action for canagliflozin, but
      not for its analogs dapagliflozin and empagliflozin. Canagliflozin inhibited the
      glutamate dehydrogenase (GDH) and mitochondrial electron transport chain (ETC)
      complex I at clinically relevant concentrations. This dual inhibition
      specifically prevented replenishment of tricarboxylic acid cycle metabolites by
      glutamine (anaplerosis) and thus altered amino acid pools by increasing
      compensatory transamination reactions. Consequently, canagliflozin caused a
      characteristic intracellular accumulation of glutamine, glutamate and alanine in
      confluent, quiescent RPTEC/TERT1. Canagliflozin, but none of the classical ETC
      inhibitors, induced cytotoxicity at particularly low concentrations in
      proliferating RPTEC/TERT1, serving as model for proximal tubule regeneration in
      situ. This finding is testimony of the strong dependence of proliferating cells
      on glutamine anaplerosis via GDH. Our discovery of canagliflozin-mediated
      simultaneous inhibition of GDH and ETC complex I in renal cells at clinically
      relevant concentrations, and their particular susceptibility to necrotic cell
      death during proliferation, provides a mechanistic rationale for the adverse
      effects observed especially in patients with preexisting chronic kidney disease
      or previous kidney injury characterized by sustained regenerative tubular
      epithelial cell proliferation.

PMID- 29445146
TI  - Dural effects of oxidative stress on cardiomyogenesis via Gata4 transcription and
      protein ubiquitination.
AB  - Oxidative stress generates reactive oxygen species (ROS) that can promote or
      inhibit cardiac differentiation of stem cells dependent on the intensity of
      stimuli as well as cellular context in redox and differentiation status. In the
      current study, we confirmed that suitable intensity of hydrogen peroxide at the
      formation stage of embryoid bodies (EBs) effectively favored the formation of
      spontaneously beating cardiomyocytes from P19 embryonal carcinoma cells.
      Mechanistic studies implicated that extrinsic ROS enhanced the Caspase-mediated
      degradation of Oct4 and Nanog, two factors that governing pluripotent property.
      Further experiments suggested that a cohort of Nanog together with histone
      deacetylase 4 (Hdac4) played a critical role in establishing and maintaining the
      silent transcriptional status of Gata4 and Nkx2.5 in undifferentiated cells.
      Thus, an impulse of hydrogen peroxide depleted Nanog and Hdac4 via a caspase
      dependent manner to ameliorate the repression on Gata4 and Nkx2.5 promoters,
      thereby generating a persistent activation on cardiac differentiation program.
      Meanwhile, we found that excessive ROS-activated JNK cascade to facilitate the
      ubiquitination and subsequent degradation of Gata4 protein. Overall, our results
      indicate that suitable ROS promotes the activation of Gata4 in transcription,
      while excessive ROS targets Gata4 protein for proteasome-dependent degradation.
      Gata4 is an important modulator balancing the promoting and inhibitory effects of
      oxidative stress on differentiation program of cardiomyogenesis.

PMID- 29445147
TI  - Long non-coding RNA PVT1 predicts poor prognosis and induces radioresistance by
      regulating DNA repair and cell apoptosis in nasopharyngeal carcinoma.
AB  - The long non-coding RNA, plasmacytoma variant translocation 1 (PVT1), is highly
      expressed in a variety of tumors, and is believed to be a potential oncogene.
      However, the role and mechanism of action of PVT1 in the carcinogenesis and
      progression of nasopharyngeal carcinomas (NPCs) remains unclear. In this study,
      for the first time, we have discovered that PVT1 shows higher expression in NPCs
      than in normal nasopharyngeal epithelial tissue, and patients with NPCs who show
      higher expression of PVT1 have worse progression-free and overall survivals.
      Additionally, we observed that the proliferation of NPC cells decreased, and
      their rate of apoptosis increased; these results indicated that the knockdown of
      PVT1 expression in the NPC cells induced radiosensitivity. Further, we have shown
      that the knockdown of PVT1 expression can induce apoptosis in the NPC cells by
      influencing the DNA damage repair pathway after radiotherapy. In general, our
      study shows that PVT1 may be a novel biomarker for prognosis and a new target for
      the treatment of NPCs. Additionally, targeting PVT1 may be a potential strategy
      for the clinical management of NPC and for the improvement of the curative effect
      of radiation in NPCs.

PMID- 29445148
TI  - Temporal requirements for ISL1 in sympathetic neuron proliferation,
      differentiation, and diversification.
AB  - Malformations of the sympathetic nervous system have been associated with
      cardiovascular instability, gastrointestinal dysfunction, and neuroblastoma. A
      better understanding of the factors regulating sympathetic nervous system
      development is critical to the development of potential therapies. Here, we have
      uncovered a temporal requirement for the LIM homeodomain transcription factor
      ISL1 during sympathetic nervous system development by the analysis of two mutant
      mouse lines: an Isl1 hypomorphic line and mice with Isl1 ablated in neural crest
      lineages. During early development, ISL1 is required for sympathetic neuronal
      fate determination, differentiation, and repression of glial differentiation,
      although it is dispensable for initial noradrenergic differentiation. ISL1 also
      plays an essential role in sympathetic neuron proliferation by controlling cell
      cycle gene expression. During later development, ISL1 is required for axon growth
      and sympathetic neuron diversification by maintaining noradrenergic
      differentiation, but repressing cholinergic differentiation. RNA-seq analyses of
      sympathetic ganglia from Isl1 mutant and control embryos, together with ISL1 ChIP
      seq analysis on sympathetic ganglia, demonstrated that ISL1 regulates directly or
      indirectly several distinct signaling pathways that orchestrate sympathetic
      neurogenesis. A number of genes implicated in neuroblastoma pathogenesis are
      direct downstream targets of ISL1. Our study revealed a temporal requirement for
      ISL1 in multiple aspects of sympathetic neuron development, and suggested Isl1 as
      a candidate gene for neuroblastoma.

PMID- 29445149
TI  - Let-7c inhibits cholangiocarcinoma growth but promotes tumor cell invasion and
      growth at extrahepatic sites.
AB  - Cholangiocarcinoma (CCA) is a cancer type with high postoperative relapse rates
      and poor long-term survival largely due to tumor invasion, distant metastasis,
      and multidrug resistance. Deregulated microRNAs (miRNAs) are implicated in
      several cancer types including CCA. The specific roles of the miRNA let-7c in
      cholangiocarcinoma are not known and need to be further elucidated. In our
      translational study we show that microRNA let-7c expression was significantly
      downregulated in human cholangiocarcinoma tissues when compared to adjacent
      tissues of the same patient. Let-7c inhibited the tumorigenic properties of
      cholangiocarcinoma cells including their self-renewal capacity and sphere
      formation in vitro and subcutaneous cancer cell growth in vivo. Ectopic let-7c
      overexpression suppressed migration and invasion capacities of cholangiocarcinoma
      cell lines in vitro, however, promoted distant invasiveness in vivo. Furthermore,
      we found that let-7c regulated the aforementioned malignant biological
      properties, at least in part, through regulation of EZH2 protein expression and
      through the DVL3/beta-catenin axis. The miRNA let-7c thus plays an important dual
      role in regulating tumorigenic and metastatic abilities of human
      cholangiocarcinoma through mechanisms involving EZH2 protein and the DVL3/beta
      catenin axis.

PMID- 29445150
TI  - Loss of NDRG2 in liver microenvironment inhibits cancer liver metastasis by
      regulating tumor associate macrophages polarization.
AB  - The liver is the predominant metastatic site for several types of malignancies.
      Tumor-associated macrophages (TAMs) in the liver play crucial roles in the
      metastasis process. Shifting tumor-promoting M2-like TAMs toward the M1-like
      phenotype, which exerts tumor suppressor functions via phagocytosis and the
      secretion of inhibitory factors, may be a potential therapeutic strategy for
      liver cancer metastasis treatment.We first cloned NDRG2 (N-myc downstream
      regulated gene 2) and verified its tumor suppressor role in multiple solid
      tumors, including colorectal cancer and hepatocellular carcinoma. However, its
      role in the tumor-associated liver microenvironment, especially in TAMs, has not
      been illustrated. By establishing a liver cancer metastasis model in wild-type
      (WT) and Ndrg2 knockout (Ndrg2-/-) mice, we found that the loss of the tumor
      suppressor Ndrg2 in liver microenvironment significantly suppressed the growth of
      liver colonies. In addition, this process was accompanied by a higher proportion
      of M1-like TAM infiltration in Ndrg2-/- mice. Interestingly, bone marrow (BM)
      transplantation revealed that BM-derived macrophages (BMDMs) rather than liver
      resident Kupffer cells were responsible for the inhibitory effect. We further
      demonstrated that loss of Ndrg2 influenced TAM polarization via the NF-kappaB
      pathway. Inhibition of IkappaBalpha phosphorylation in cancer cell-conditioned
      medium-stimulated BMDMs decreased M1 marker expression in Ndrg2-/- macrophages.
      Finally, in vitro, invasion, migration, and proliferation assays confirmed that
      NF-kappaB participated in the tumor suppressor function of Ndrg2-/- macrophages.
      Collectively, our findings highlight the role of NDRG2 in the regulation of TAM
      polarization and its function in promoting cancer liver metastasis.

PMID- 29445151
TI  - The vesicle trafficking regulator PN_SCD1 is demethylated and overexpressed in
      florets of apomictic Paspalum notatum genotypes.
AB  - Apomixis (asexual reproduction through seeds) is considered a deviation of the
      sexual reproductive pathway leading to the development of clonal progenies
      genetically identical to the mother plant. Here we used the Methylation-Sensitive
      Amplification Polymorphism (MSAP) technique to characterize cytosine methylation
      patterns occurring in florets of sexual and aposporous Paspalum notatum
      genotypes, in order to identify epigenetically-controlled genes putatively
      involved in apomixis development. From twelve polymorphic MSAP-derived sequences,
      one (PN_6.6, later renamed PN_SCD1) was selected due to its relevant annotation
      and differential representation in apomictic and sexual floral transcriptome
      libraries. PN_SCD1 encodes the DENN domain/WD repeat-containing protein SCD1,
      which interacts with RAB GTPases- and/or MAPKs to promote specialized cell
      division, functions in clathrin-mediated membrane transport and acts as potential
      substrate receptor of CUL4 E3 ubiquitin ligases. Quantitative RT-PCR and
      comparative RNAseq analyses of laser microdissected nucellar cells confirmed
      PN_SCD1 upregulation in florets of apomictic plants and revealed that
      overexpression takes place just before the onset of apospory initials. Moreover,
      we found that several SCD1 molecular partners are expressed in P. notatum florets
      and upregulated in apomictic plants. Our results disclosed a specific vesicle
      trafficking molecular pathway epigenetically modulated during apomixis.

PMID- 29445152
TI  - Fourier transform spectrometer on silicon with thermo-optic non-linearity and
      dispersion correction.
AB  - Miniaturized integrated spectrometers will have unprecedented impact on
      applications ranging from unmanned aerial vehicles to mobile phones, and silicon
      photonics promises to deliver compact, cost-effective devices. Mirroring its
      ubiquitous free-space counterpart, a silicon photonics-based Fourier transform
      spectrometer (Si-FTS) can bring broadband operation and fine resolution to the
      chip scale. Here we present the modeling and experimental demonstration of a
      thermally tuned Si-FTS accounting for dispersion, thermo-optic non-linearity, and
      thermal expansion. We show how these effects modify the relation between the
      spectrum and interferogram of a light source and we develop a quantitative
      correction procedure through calibration with a tunable laser. We retrieve a
      broadband spectrum (7 THz around 193.4 THz with 0.38-THz resolution consuming 2.5
      W per heater) and demonstrate the Si-FTS resilience to fabrication variations-a
      major advantage for large-scale manufacturing. Providing design flexibility and
      robustness, the Si-FTS is poised to become a fundamental building block for on
      chip spectroscopy.

PMID- 29445153
TI  - Development of a chimeric Zika vaccine using a licensed live-attenuated
      flavivirus vaccine as backbone.
AB  - The global spread of Zika virus (ZIKV) and its unexpected association with
      congenital defects necessitates the rapid development of a safe and effective
      vaccine. Here we report the development and characterization of a recombinant
      chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E
      proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine
      SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and
      genetic stability in vitro, while exhibiting an attenuation phenotype in multiple
      animal models. Remarkably, immunization of mice and rhesus macaques with a single
      dose of ChinZIKV elicits robust and long-lasting immune responses, and confers
      complete protection against ZIKV challenge. Significantly, female mice immunized
      with ChinZIKV are protected against placental and fetal damage upon ZIKV
      challenge during pregnancy. Overall, our study provides an alternative vaccine
      platform in response to the ZIKV emergency, and the safety, immunogenicity, and
      protection profiles of ChinZIKV warrant further clinical development.

PMID- 29445154
TI  - Interleukin 4 modulates microglia homeostasis and attenuates the early slowly
      progressive phase of amyotrophic lateral sclerosis.
AB  - Microglia activation is a commonly pathological hallmark of neurodegenerative
      diseases, such as amyotrophic lateral sclerosis (ALS), a devastating disorder
      characterized by a selective motor neurons degeneration. Whether such activation
      might represent a causal event rather than a secondary epiphenomenon remains
      elusive. Here, we show that CNS-delivery of IL-4-via a lentiviral-mediated gene
      therapy strategy-skews microglia to proliferate, inducing these cells to adopt
      the phenotype of slowly proliferating cells. Transcriptome analysis revealed that
      IL-4-treated microglia express a broad number of genes normally encoded by
      embryonic microglia. Since embryonic microglia sustain CNS development, we then
      hypothesized that turning adult microglia to acquire such phenotype via IL-4
      might be an efficient in vivo strategy to sustain motor neuron survival in ALS.
      IL-4 gene therapy in SOD1G93A mice resulted in a general amelioration of clinical
      outcomes during the early slowly progressive phase of the disease. However, such
      approach did not revert neurodegenerative processes occurring in the late and
      fast progressing phase of the disease.

PMID- 29445155
TI  - The cytotoxicity of coxsackievirus B3 is associated with a blockage of autophagic
      flux mediated by reduced syntaxin 17 expression.
AB  - Coxsackievirus B3 (CVB3) is an important human pathogen linked to cardiac
      arrhythmias and acute heart failure. CVB3 infection has been reported to induce
      the formation of autophagosomes that support the viral replication in host cells.
      Interestingly, our study shows that the accumulation of autophagosomes during
      CVB3 infection is caused by a blockage of autophagosome-lysosome fusion rather
      than the induction of autophagosome biogenesis. Moreover, CVB3 decreases the
      transcription and translation of syntaxin 17 (STX17), a SNARE (soluble N
      ethylmaleimide-sensitive factor activating protein receptor) protein involved in
      autophagosome-lysosome fusion. Overexpression of STX17 restored the autophagic
      flux, alleviated the virus-induced lysosomal dysfunction, and decreased the
      apoptosis induced by CVB3 infection in HeLa cells. Taken together, our results
      suggest that CVB3 infection impairs the autophagic flux by blocking autophagosome
      lysosome fusion. These findings thus point to potential new therapeutic
      strategies targeting STX17 or autophagosome-lysosome fusion for treating CVB3
      associated diseases.

PMID- 29445156
TI  - Probing electrochemical reactions in organic cathode materials via in operando
      infrared spectroscopy.
AB  - Organic materials are receiving an increasing amount of attention as electrode
      materials for future post lithium-ion batteries due to their versatility and
      sustainability. However, their electrochemical reaction mechanism has seldom been
      investigated. This is a direct consequence of a lack of straightforward and
      broadly available analytical techniques. Herein, a straightforward in operando
      attenuated total reflectance infrared spectroscopy method is developed that
      allows visualization of changes of all infrared active bands that occur as a
      consequence of reduction/oxidation processes. In operando infrared spectroscopy
      is applied to the analysis of three different organic polymer materials in
      lithium batteries. Moreover, this in operando method is further extended to
      investigation of redox reaction mechanism of poly(anthraquinonyl sulfide) in a
      magnesium battery, where a reduction of carbonyl bond is demonstrated as a
      mechanism of electrochemical activity. Conclusions done by the in operando
      results are complemented by synthesis of model compound and density functional
      theory calculation of infrared spectra.

PMID- 29445157
TI  - Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal
      fenestration with round window membrane inoculation.
AB  - Cochlear gene therapy holds promise for the treatment of genetic deafness.
      Assessing its impact in adult murine models of hearing loss, however, has been
      hampered by technical challenges that have made it difficult to establish a
      robust method to deliver transgenes to the mature murine inner ear. Here in we
      demonstrate the feasibility of a combined round window membrane injection and
      semi-circular canal fenestration technique in the adult cochlea. Injection of
      both AAV2/9 and AAV2/Anc80L65 via this approach in P15-16 and P56-60 mice permits
      robust eGFP transduction of virtually all inner hair cells throughout the cochlea
      with variable transduction of vestibular hair cells. Auditory thresholds are not
      compromised. Transduction rate and cell tropism is primarily influenced by viral
      titer and AAV serotype but not age at injection. This approach is safe, versatile
      and efficient. Its use will facilitate studies using cochlear gene therapy in
      murine models of hearing loss over a wide range of time points.

PMID- 29445159
TI  - Microfluidic cell sorting by stiffness to examine heterogenic responses of cancer
      cells to chemotherapy.
AB  - Cancers consist of a heterogeneous populations of cells that may respond
      differently to treatment through drug-resistant sub-populations. The scarcity of
      these resistant sub-populations makes it challenging to understand how to counter
      their resistance. We report a label-free microfluidic approach to separate cancer
      cells treated with chemotherapy into sub-populations enriched in chemoresistant
      and chemosensitive cells based on the differences in cellular stiffness. The
      sorting approach enabled analysis of the molecular distinctions between resistant
      and sensitive cells. Consequently, the role of multiple mechanisms of drug
      resistance was identified, including decreased sensitivity to apoptosis, enhanced
      metabolism, and extrusion of drugs, and, for the first time, the role of estrogen
      receptor in drug resistance of leukemia cells. To validate these findings,
      several inhibitors for the identified resistance pathways were tested with
      chemotherapy to increase cytotoxicity sevenfold. Thus, microfluidic sorting can
      identify molecular mechanisms of drug resistance to examine heterogeneous
      responses of cancers to therapies.

PMID- 29445158
TI  - ACKR2 in hematopoietic precursors as a checkpoint of neutrophil release and anti
      metastatic activity.
AB  - Atypical chemokine receptors (ACKRs) are regulators of leukocyte traffic,
      inflammation, and immunity. ACKR2 is a scavenger for most inflammatory CC
      chemokines and is a negative regulator of inflammation. Here we report that ACKR2
      is expressed in hematopoietic precursors and downregulated during myeloid
      differentiation. Genetic inactivation of ACKR2 results in increased levels of
      inflammatory chemokine receptors and release from the bone marrow of neutrophils
      with increased anti-metastatic activity. In a model of NeuT-driven primary
      mammary carcinogenesis ACKR2 deficiency is associated with increased primary
      tumor growth and protection against metastasis. ACKR2 deficiency results in
      neutrophil-mediated protection against metastasis in mice orthotopically
      transplanted with 4T1 mammary carcinoma and intravenously injected with B16F10
      melanoma cell lines. Thus, ACKR2 is a key regulator (checkpoint) of mouse myeloid
      differentiation and function and its targeting unleashes the anti-metastatic
      activity of neutrophils in mice.

PMID- 29445160
TI  - Optomechanics with a hybrid carbon nanotube resonator.
AB  - In just 20 years of history, the field of optomechanics has achieved impressive
      progress, stepping into the quantum regime just 5 years ago. Such remarkable
      advance relies on the technological revolution of nano-optomechanical systems,
      whose sensitivity towards thermal decoherence is strongly limited due to their
      ultra-low mass. Here we report a hybrid approach pushing nano-optomechanics to
      even lower scales. The concept relies on synthesising an efficient optical
      scatterer at the tip of singly clamped carbon nanotube resonators. We demonstrate
      high signal-to-noise motion readout and record force sensitivity, two orders of
      magnitude below the state of the art. Our work opens the perspective to extend
      quantum experiments and applications at room temperature.

PMID- 29445161
TI  - Anti-fouling graphene-based membranes for effective water desalination.
AB  - The inability of membranes to handle a wide spectrum of pollutants is an
      important unsolved problem for water treatment. Here we demonstrate water
      desalination via a membrane distillation process using a graphene membrane where
      water permeation is enabled by nanochannels of multilayer, mismatched, partially
      overlapping graphene grains. Graphene films derived from renewable oil exhibit
      significantly superior retention of water vapour flux and salt rejection rates,
      and a superior antifouling capability under a mixture of saline water containing
      contaminants such as oils and surfactants, compared to commercial distillation
      membranes. Moreover, real-world applicability of our membrane is demonstrated by
      processing sea water from Sydney Harbour over 72 h with macroscale membrane size
      of 4 cm2, processing ~0.5 L per day. Numerical simulations show that the channels
      between the mismatched grains serve as an effective water permeation route. Our
      research will pave the way for large-scale graphene-based antifouling membranes
      for diverse water treatment applications.

PMID- 29445162
TI  - MYCN drives glutaminolysis in neuroblastoma and confers sensitivity to an ROS
      augmenting agent.
AB  - Heightened aerobic glycolysis and glutaminolysis are characteristic metabolic
      phenotypes in cancer cells. Neuroblastoma (NBL), a devastating pediatric cancer,
      is featured by frequent genomic amplification of MYCN, a member of the Myc
      oncogene family that is primarily expressed in the early stage of embryonic
      development and required for neural crest development. Here we report that an
      enriched glutaminolysis gene signature is associated with MYCN amplification in
      children with NBL. The partial knockdown of MYCN suppresses glutaminolysis in NBL
      cells. Conversely, forced overexpression of MYCN in neural crest progenitor cells
      enhances glutaminolysis. Importantly, glutaminolysis induces oxidative stress by
      producing reactive oxygen species (ROS), rendering NBL cells sensitive to ROS
      augmentation. Through a small-scale metabolic-modulator screening, we have found
      that dimethyl fumarate (DMF), a Food and Drug Administration-approved drug for
      multiple sclerosis, suppresses NBL cell proliferation in vitro and tumor growth
      in vivo. DMF suppresses NBL cell proliferation through inducing ROS and
      subsequently suppressing MYCN expression, which is rescued by an ROS scavenger.
      Our findings suggest that the metabolic modulation and ROS augmentation could be
      used as novel strategies in treating NBL and other MYC-driven cancers.

PMID- 29445163
TI  - Plasma and urinary metabolomic profiles of Down syndrome correlate with
      alteration of mitochondrial metabolism.
AB  - Down syndrome (DS) is caused by the presence of a supernumerary copy of the human
      chromosome 21 (Hsa21) and is the most frequent genetic cause of intellectual
      disability (ID). Key traits of DS are the distinctive facies and cognitive
      impairment. We conducted for the first time an analysis of the Nuclear Magnetic
      Resonance (NMR)-detectable part of the metabolome in plasma and urine samples,
      studying 67 subjects with DS and 29 normal subjects as controls selected among DS
      siblings. Multivariate analysis of the NMR metabolomic profiles showed a clear
      discrimination (up to of 80% accuracy) between the DS and the control groups. The
      univariate analysis of plasma and urine revealed a significant alteration for
      some interesting metabolites. Remarkably, most of the altered concentrations were
      consistent with the 3:2 gene dosage model, suggesting effects caused by the
      presence of three copies of Hsa21 rather than two: DS/normal ratio in plasma was
      1.23 (pyruvate), 1.47 (succinate), 1.39 (fumarate), 1.33 (lactate), 1.4
      (formate). Several significantly altered metabolites are produced at the
      beginning or during the Krebs cycle. Accounting for sex, age and fasting state
      did not significantly affect the main result of both multivariate and univariate
      analysis.

PMID- 29445164
TI  - Inactivation of TRPM7 kinase in mice results in enlarged spleens, reduced T-cell
      proliferation and diminished store-operated calcium entry.
AB  - T lymphocytes enlarge (blast) and proliferate in response to antigens in a
      multistep program that involves obligatory cytosolic calcium elevations. Store
      operated calcium entry (SOCE) pathway is the primary source of Ca2+ in these
      cells. Here, we describe a novel modulator of blastogenesis, proliferation and
      SOCE: the TRPM7 channel kinase. TRPM7 kinase-dead (KD) K1646R knock-in mice
      exhibited splenomegaly and impaired blastogenic responses elicited by
      PMA/ionomycin or anti-CD3/CD28 antibodies. Splenic T-cell proliferation in vitro
      was weaker in the mutant compared to wildtype littermates. TRPM7 current
      magnitudes in WT and KD mouse T cells were, however, similar. We tested the
      dependence of T-cell proliferation on external Ca2+ and Mg2+ concentrations. At a
      fixed [Mg2+o] of ~0.4 mM, Ca2+o stimulated proliferation with a steep
      concentration dependence and vice versa, at a fixed [Ca2+o] of ~0.4 mM, Mg2+o
      positively regulated proliferation but with a shallower dependence. Proliferation
      was significantly lower in KD mouse than in wildtype at all Ca2+ and Mg2+
      concentrations. Ca2+ elevations elicited by anti-CD3 antibody were diminished in
      KD mutant T cells and SOCE measured in activated KD splenocytes was reduced.
      These results demonstrate that a functional TRPM7 kinase supports robust SOCE,
      blastogenesis and proliferation, whereas its inactivation suppresses these
      cellular events.

PMID- 29445166
TI  - Plastic pollution of the world's seas and oceans as a contemporary challenge in
      ocean governance.
AB  - The pervasive nature of marine plastic pollution was highlighted at the recent
      United Nations Environment Assembly. This meeting saw strong commitments for
      action, but at the same time reinforced the challenges for contemporary ocean
      governance in addressing marine plastic pollution.

PMID- 29445165
TI  - 53BP1 can limit sister-chromatid rupture and rearrangements driven by a distinct
      ultrafine DNA bridging-breakage process.
AB  - Chromosome missegregation acts as one of the driving forces for chromosome
      instability and cancer development. Here, we find that in human cancer cells,
      HeLa and U2OS, depletion of 53BP1 (p53-binding protein 1) exacerbates chromosome
      non-disjunction resulting from a new type of sister-chromatid intertwinement,
      which is distinct from FANCD2-associated ultrafine DNA bridges (UFBs) induced by
      replication stress. Importantly, the sister DNA intertwinements trigger gross
      chromosomal rearrangements through a distinct process, named sister-chromatid
      rupture and bridging. In contrast to conventional anaphase bridge-breakage
      models, we demonstrate that chromatid axes of the intertwined sister-chromatids
      rupture prior to the breakage of the DNA bridges. Consequently, the ruptured
      sister arms remain tethered and cause signature chromosome rearrangements,
      including whole-arm (Robertsonian-like) translocation/deletion and isochromosome
      formation. Therefore, our study reveals a hitherto unreported chromatid damage
      phenomenon mediated by sister DNA intertwinements that may help to explain the
      development of complex karyotypes in tumour cells.

PMID- 29445167
TI  - Prognostic significance of nephrectomy in metastatic renal cell carcinoma treated
      with systemic cytokine or targeted therapy: A 16-year retrospective analysis.
AB  - We compared progression-free survival (PFS) and overall survival (OS) among 292
      metastatic renal cell carcinoma (mRCC) patients either undergoing nephrectomy
      (Nx, 61.6%) or not (non-Nx, 38.4%), stratified according to the MSKCC and Heng
      risk models, treated with either immunotherapy (IT, 45.2%) or targeted therapy
      (TT, 54.8%) between 2000 and 2015. During the follow-up duration of 16.6 months,
      PFS/OS of the Nx (6.0/30 months) and non-Nx (3.0/6.0 months) groups were
      significantly different despite differences among baseline parameters (p < 0.05).
      The intermediate- and poor-risk patients defined using either model showed
      significantly longer PFS and OS in the Nx group than in the non-Nx group (p <
      0.05). After stratifying groups by systemic therapy and risk models, both the Nx
      and non-Nx groups showed no significant differences in intermediate and poor-risk
      models (p > 0.05). In both synchronous and metachronous mRCC patients, both PFS
      and OS showed similar survivals; the Nx group had significantly longer PFS and OS
      than the non-Nx group, even after considering each systemic therapy and
      prognostic model. Nx showed a significant positive benefit in PFS and OS compared
      to no Nx upon patient stratification according to the MSKCC and Heng risk models.
      The metastatic type did not significantly affect survival between the two groups.

PMID- 29445168
TI  - Biomimetic light-harvesting funnels for re-directioning of diffuse light.
AB  - Efficient sunlight harvesting and re-directioning onto small areas has great
      potential for more widespread use of precious high-performance photovoltaics but
      so far intrinsic solar concentrator loss mechanisms outweighed the benefits. Here
      we present an antenna concept allowing high light absorption without high
      reabsorption or escape-cone losses. An excess of randomly oriented pigments
      collects light from any direction and funnels the energy to individual acceptors
      all having identical orientations and emitting ~90% of photons into angles
      suitable for total internal reflection waveguiding to desired energy converters
      (funneling diffuse-light re-directioning, FunDiLight). This is achieved using
      distinct molecules that align efficiently within stretched polymers together with
      others staying randomly orientated. Emission quantum efficiencies can be >80% and
      single-foil reabsorption <0.5%. Efficient donor-pool energy funneling, dipole re
      orientation, and ~1.5-2 nm nearest donor-acceptor transfer occurs within hundreds
      to ~20 ps. Single-molecule 3D-polarization experiments confirm nearly parallel
      emitters. Stacked pigment selection may allow coverage of the entire solar
      spectrum.

PMID- 29445169
TI  - Shape anisotropy revisited in single-digit nanometer magnetic tunnel junctions.
AB  - Nanoscale magnetic tunnel junctions play a pivotal role in magnetoresistive
      random access memories. Successful implementation depends on a simultaneous
      achievement of low switching current for the magnetization switching by spin
      transfer torque and high thermal stability, along with a continuous reduction of
      junction size. Perpendicular easy-axis CoFeB/MgO stacks possessing interfacial
      anisotropy have paved the way down to 20-nm scale, below which a new approach
      needs to be explored. Here we show magnetic tunnel junctions that satisfy the
      requirements at ultrafine scale by revisiting shape anisotropy, which is a
      classical part of magnetic anisotropy but has not been fully utilized in the
      current perpendicular systems. Magnetization switching solely driven by current
      is achieved for junctions smaller than 10 nm where sufficient thermal stability
      is provided by shape anisotropy without adopting new material systems. This work
      is expected to push forward the development of magnetic tunnel junctions toward
      single-digit nm-scale nano-magnetics/spintronics.

PMID- 29445170
TI  - BRM270 inhibits cancer stem cell maintenance via microRNA regulation in
      chemoresistant A549 lung adenocarcinoma cells.
AB  - Chemotherapy is a standard treatment for non-small-cell lung cancer (NSCLC).
      However, the dose-limiting toxicity of drugs and the development of
      chemoresistance are major clinical challenges to successful management of NSCLC.
      Asian traditional medicine is gaining global attention as a non-toxic alternative
      to chemotherapy. BRM270 is an extract formulated from seven Asian medicinal
      plants that has been shown to inhibit tumor cell proliferation in diverse cancer
      types. We previously demonstrated that BRM270 suppresses tumorigenesis by
      negatively regulating nuclear factor-kappaB signaling in multidrug-resistant
      cancer stem cells (CSCs). In this study we report that the growth, migration, and
      invasion of normal human lung adenocarcinoma cells and their chemoresistant
      derivatives was inhibited by BRM270 treatment. Notably, BRM270 was found to
      modulate CSC self-renewal and tumor-initiating capacity via positive regulation
      of the miRNA-128. Thus, combination therapy with miRNA-128 and BRM270 may be an
      effective treatment strategy for chemoresistant NSCLC.

PMID- 29445171
TI  - Electrophysiological evidence of memory-based detection of auditory regularity
      violations in anesthetized mice.
AB  - In humans, automatic change detection is reflected by an electrical brain
      response called mismatch negativity (MMN). Mismatch response is also elicited in
      mice, but it is unclear to what extent it is functionally similar to human MMN.
      We investigated this possible similarity by recording local field potentials from
      the auditory cortex of anesthetized mice. First, we tested whether the response
      to stimulus changes reflected the detection of regularity violations or
      adaptation to standard stimuli. Responses obtained from an oddball condition,
      where occasional changes in frequency were presented amongst of a standard sound,
      were compared to responses obtained from a control condition, where no
      regularities existed. To test whether the differential response to the deviant
      sounds in the oddball condition is dependent on sensory memory, responses from
      the oddball condition using 375 ms and 600 ms inter-stimulus intervals (ISI) were
      compared. We found a differential response to deviant sounds which was larger
      with the shorter than the longer ISI. Furthermore, the oddball deviant sound
      elicited larger response than the same sound in the control condition. These
      results demonstrate that the mismatch response in mice reflects detection of
      regularity violations and sensory memory function, as the human MMN.

PMID- 29445172
TI  - Rational cell culture optimization enhances experimental reproducibility in
      cancer cells.
AB  - Optimization of experimental conditions is critical in ensuring robust
      experimental reproducibility. Through detailed metabolomic analysis we found that
      cell culture conditions significantly impacted on glutaminase (GLS1) sensitivity
      resulting in variable sensitivity and irreproducibility in data. Baseline
      metabolite profiling highlighted that untreated cells underwent significant
      changes in metabolic status. Both the extracellular levels of glutamine and
      lactate and the intracellular levels of multiple metabolites changed drastically
      during the assay. We show that these changes compromise the robustness of the
      assay and make it difficult to reproduce. We discuss the implications of the
      cells' metabolic environment when studying the effects of perturbations to cell
      function by any type of inhibitor. We then devised 'metabolically rationalized
      standard' assay conditions, in which glutaminase-1 inhibition reduced glutamine
      metabolism differently in both cell lines assayed, and decreased the
      proliferation of one of them. The adoption of optimized conditions such as the
      ones described here should lead to an improvement in reproducibility and help
      eliminate false negatives as well as false positives in these assays.

PMID- 29445173
TI  - Tuning piezoelectric properties through epitaxy of La2Ti2O7 and related thin
      films.
AB  - Current piezoelectric sensors and actuators are limited to operating temperatures
      less than ~200  degrees C due to the low Curie temperature of the piezoelectric
      material. Strengthening the piezoelectric coupling of high-temperature
      piezoelectric materials, such as La2Ti2O7 (LTO), would allow sensors to operate
      across a broad temperature range. The crystalline orientation and piezoelectric
      coupling direction of LTO thin films can be controlled by epitaxial matching to
      SrTiO3(001), SrTiO3(110), and rutile TiO2(110) substrates via pulsed laser
      deposition. The structure and phase purity of the films are investigated by x-ray
      diffraction and scanning transmission electron microscopy. Piezoresponse force
      microscopy is used to measure the in-plane and out-of-plane piezoelectric
      coupling in the films. The strength of the out-of-plane piezoelectric coupling
      can be increased when the piezoelectric direction is rotated partially out-of
      plane via epitaxy. The strongest out-of-plane coupling is observed for
      LTO/STO(001). Deposition on TiO2(110) results in epitaxial La2/3TiO3, an
      orthorhombic perovskite of interest as a microwave dielectric material and an ion
      conductor. La2/3TiO3 can be difficult to stabilize in bulk form, and epitaxial
      stabilization on TiO2(110) is a promising route to realize La2/3TiO3 for both
      fundamental studies and device applications. Overall, these results confirm that
      control of the crystalline orientation of epitaxial LTO-based materials can
      govern the resulting functional properties.

PMID- 29445175
TI  - A novel autophagy inhibitor berbamine blocks SNARE-mediated autophagosome
      lysosome fusion through upregulation of BNIP3.
AB  - Increasing evidences reveal that autophagy inhibitor could enhance the effect of
      chemotherapy to cancer. However, few autophagy inhibitors are currently approved
      for clinical application in humans. Berbamine (BBM) is a natural compound
      extracted from traditional Chinese medicine that is widely used for treatment of
      a variety of diseases without any obvious side effects. Here we found that BBM is
      a novel auophagy inhibitor, which potently induced the accumulation of
      autophagosomes by inhibiting autophagosome-lysosome fusion in human breast cancer
      cells. Mechanistically, we found that BBM blocked autophagosome-lysosome fusion
      by inhibiting the interaction of SNAP29 and VAMP8. Furthermore, BBM induced
      upregulation of BNIP3 and the interaction between SNAP29 and BNIP3. BNIP3
      depletion or SNAP29 overexpression abrogated BBM-mediated blockade of
      autophagosome-lysosome fusion through the interaction between SNAP29 and VAMP8,
      whereas BNIP3 overexpression blocked autophagosome-lysosome fusion through
      inhibition of the interaction between SNAP29 and VAMP8. These findings suggest
      that upregulation of BNIP3 and interaction between BNIP3 and SNAP29 could be
      involved in BBM-mediated blockade of autophagosome-lysosome fusion through
      inhibition of the interaction between SNAP29 and VAMP8. Our findings identify the
      critical role of BNIP3 in blockade of autophagosome-lysosome fusion mediated by
      BBM, and suggest that BBM could potentially be further developed as a novel
      autophagy inhibitor, which could enhance the effect of chemotherapy to cancer.

PMID- 29445174
TI  - A spatial gradient of bacterial diversity in the human oral cavity shaped by
      salivary flow.
AB  - Spatial and temporal patterns in microbial communities provide insights into the
      forces that shape them, their functions and roles in health and disease. Here, we
      used spatial and ecological statistics to analyze the role that saliva plays in
      structuring bacterial communities of the human mouth using >9000 dental and
      mucosal samples. We show that regardless of tissue type (teeth, alveolar mucosa,
      keratinized gingiva, or buccal mucosa), surface-associated bacterial communities
      vary along an ecological gradient from the front to the back of the mouth, and
      that on exposed tooth surfaces, the gradient is pronounced on lingual compared to
      buccal surfaces. Furthermore, our data suggest that this gradient is attenuated
      in individuals with low salivary flow due to Sjogren's syndrome. Taken together,
      our findings imply that salivary flow influences the spatial organization of
      microbial communities and that biogeographical patterns may be useful for
      understanding host physiological processes and for predicting disease.

PMID- 29445176
TI  - Thermally-Conductive and Mechanically-Robust Graphene Nanoplatelet Reinforced UO2
      Composite Nuclear Fuels.
AB  - Low thermal transport behavior along the radial direction of nuclear fuel pellets
      and pellet-cladding mechanical interaction significantly impact fuel performance
      and the safety of current nuclear energy systems. Here we report a new strategy
      of advanced fuel design in which highly thermally-conductive and mechanically
      robust graphene nanoplatelets are incorporated into UO2 fuel matrix to improve
      fuel thermal-mechanical properties. The 2D geometry of the graphene nanoplatelets
      enables a unique lamellar structure upon fuel consolidation by spark plasma
      sintering. The thermal conductivity along the radial direction of the sintered
      fuel pellets at room temperature reaches 12.7 and 19.1 wm-1K-1 at 1 wt.% and 5
      wt.% loadings of the graphene nanoplatelets, respectively, representing at least
      74% and 162% enhancements as compared to pure UO2 fuel pellets. Indentation
      testing suggests great capability of the 2D graphene nanoplatelets to deflect and
      pin crack propagation, drastically improving the crack propagation resistance of
      fuel matrix. The estimated indentation fracture toughness reaches 3.5 MPa.m1/2 by
      1 wt.% loading of graphene nano-platelets, representing a 150% improvement over
      1.4 MPa.m1/2 for pure UO2 fuel pellets. Isothermal annealing of the composite
      fuel indicates that the graphene nano-platelet is able to retain its structure
      and properties against reaction with UO2 matrix up to 1150  degrees C.

PMID- 29445177
TI  - Validating a breast cancer score in Spanish women. The MCC-Spain study.
AB  - A breast-risk score, published in 2016, was developed in white-American women
      using 92 genetic variants (GRS92), modifiable and non-modifiable risk factors.
      With the aim of validating the score in the Spanish population, 1,732 breast
      cancer cases and 1,910 controls were studied. The GRS92, modifiable and non
      modifiable risk factor scores were estimated via logistic regression. SNPs
      without available genotyping were simulated as in the aforementioned 2016 study.
      The full model score was obtained by combining GRS92, modifiable and non
      modifiable risk factor scores. Score performances were tested via the area under
      the ROC curve (AUROC), net reclassification index (NRI) and integrated
      discrimination improvement (IDI). Compared with non-modifiable and modifiable
      factor scores, GRS92 had higher discrimination power (AUROC: 0.6195, 0.5885 and
      0.5214, respectively). Adding the non-modifiable factor score to GRS92 improved
      patient classification by 23.6% (NRI = 0.236), while the modifiable factor score
      only improved it by 7.2%. The full model AUROC reached 0.6244. A simulation study
      showed the ability of the full model for identifying women at high risk for
      breast cancer. In conclusion, a model combining genetic and risk factors can be
      used for stratifying women by their breast cancer risk, which can be applied to
      individualizing genetic counseling and screening recommendations.

PMID- 29445178
TI  - The effect of Clostridium butyricum on symptoms and fecal microbiota in diarrhea
      dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled
      trial.
AB  - Irritable bowel syndrome (IBS) is a common disorder in gastrointestinal system
      and impairs the quality of life of the patients. Clostridium butyricum (CB) is a
      probiotics that has been used in several gastrointestinal diseases. The efficacy
      of CB in treating IBS is still unknown. This prospective, multi-centre,
      randomized, double-blind, placebo-controlled trial aimed to assess the efficacy
      and safety of CB in treating diarrhea-predominant IBS (IBS-D) and analyze the
      fecal microbiota after treatment. Two hundred patients with IBS-D were recruited
      and were given CB or placebo for 4 weeks. End points included change from
      baseline in IBS symptoms, quality of life, stool consistency and frequency.
      Compared with placebo, CB is effective in improving the overall IBS-D symptoms (
      62.12 +/- 74.00 vs. -40.74 +/- 63.67, P = 0.038) as well as quality of life
      (7.232 +/- 14.06 vs. 3.159 +/- 11.73, P = 0.032) and stool frequency (-1.602 +/-
      1.416 vs. -1.086 +/- 1.644, P = 0.035). The responder rates are found higher in
      CB compared with the placebo (44.76% vs. 30.53%, P = 0.042). The change in fecal
      microbiota was analyzed and function pathways of CB in treating IBS-D were
      predicted. In conclusion, CB improves overall symptoms, quality of life and stool
      frequency in IBS-D patients and is considered to be used as a probiotics in
      treating IBS-D clinically.

PMID- 29445179
TI  - Long noncoding RNA GAS5 promotes bladder cancer cells apoptosis through
      inhibiting EZH2 transcription.
AB  - Aberrant expression of long noncoding RNA GAS5 in bladder cancer (BC) cells was
      identified in recent studies. However, the regulatory functions and underlying
      molecular mechanisms of GAS5 in BC development remain unclear. Here, we confirmed
      that there was a negative correlation between GAS5 level and bladder tumor
      clinical stage. Functionally, overexpression of GAS5 reduced cell viability and
      induced cell apoptosis in T24 and EJ bladder cancer cells. Mechanistically, GAS5
      effectively repressed EZH2 transcription by directly interacting with E2F4 and
      recruiting E2F4 to EZH2 promoter. We previously reported that miR-101 induced the
      apoptosis of BC cells by inhibiting the expression of EZH2. Interestingly, the
      present study showed that downregulation of EZH2 by GAS5 resulted in
      overexpression of miR-101 in T24 and EJ cells. Furthermore, the level of GAS5 was
      increased under the treatment of Gambogic acid (GA), a promising natural anti
      cancer compound, whereas knockdown of GAS5 suppressed the inhibitory effect of GA
      on cell viability and abolished GA-induced apoptosis in T24 and EJ cells. Taken
      together, our findings demonstrated a tumor-suppressor role of GAS5 by inhibiting
      EZH2 on transcriptional level, and additionally provided a novel therapeutic
      strategy for treating human bladder cancer.

PMID- 29445182
TI  - Terpene Composition Complexity Controls Secondary Organic Aerosol Yields from
      Scots Pine Volatile Emissions.
AB  - Secondary organic aerosol (SOA) impact climate by scattering and absorbing
      radiation and contributing to cloud formation. SOA models are based on studies of
      simplified chemical systems that do not account for the chemical complexity in
      the atmosphere. This study investigated SOA formation from a mixture of real
      Scots pine (Pinus sylvestris) emissions including a variety of monoterpenes and
      sesquiterpenes. SOA generation was characterized from different combinations of
      volatile compounds as the plant emissions were altered with an herbivore stress
      treatment. During active herbivore feeding, monoterpene and sesquiterpene
      emissions increased, but SOA mass yields decreased after accounting for
      absorption effects. SOA mass yields were controlled by sesquiterpene emissions in
      healthy plants. In contrast, SOA mass yields from stressed plant emissions were
      controlled by the specific blend of monoterpene emissions. Conservative estimates
      using a box model approach showed a 1.5- to 2.3-fold aerosol enhancement when the
      terpene complexity was taken into account. This enhancement was relative to the
      commonly used model monoterpene, "alpha-pinene". These results suggest that
      simplifying terpene complexity in SOA models could lead to underpredictions in
      aerosol mass loading.

PMID- 29445181
TI  - Interactions between predation and disturbances shape prey communities.
AB  - Ecological disturbances are important drivers of biodiversity patterns. Many
      biodiversity studies rely on endpoint measurements instead of following the
      dynamics that lead to those outcomes and testing ecological drivers individually,
      often considering only a single trophic level. Manipulating multiple factors
      (biotic and abiotic) in controlled settings and measuring multiple descriptors of
      multi-trophic communities could enlighten our understanding of the context
      dependency of ecological disturbances. Using model microbial communities, we
      experimentally tested the effects of imposed disturbances (i.e. increased
      dilution simulating density-independent mortality as press or pulse disturbances
      coupled with resource deprivation) on bacterial abundance, diversity and
      community structure in the absence or presence of a protist predator. We
      monitored the communities immediately before and after imposing the disturbance
      and four days after resuming the pre-disturbance dilution regime to infer
      resistance and recovery properties. The results highlight that bacterial
      abundance, diversity and community composition were more affected by predation
      than by disturbance type, resource loss or the interaction of these factors.
      Predator abundance was strongly affected by the type of disturbance imposed,
      causing temporary relief of predation pressure. Importantly, prey community
      composition differed significantly at different phases, emphasizing that endpoint
      measurements are insufficient for understanding the recovery of communities.

PMID- 29445180
TI  - Myeloid-derived interleukin-1beta drives oncogenic KRAS-NF-kappaBeta addiction in
      malignant pleural effusion.
AB  - Malignant pleural effusion (MPE) is a frequent metastatic manifestation of human
      cancers. While we previously identified KRAS mutations as molecular culprits of
      MPE formation, the underlying mechanism remained unknown. Here, we determine that
      non-canonical IKKalpha-RelB pathway activation of KRAS-mutant tumor cells
      mediates MPE development and this is fueled by host-provided interleukin IL
      1beta. Indeed, IKKalpha is required for the MPE-competence of KRAS-mutant tumor
      cells by activating non-canonical NF-kappaB signaling. IL-1beta fuels addiction
      of mutant KRAS to IKKalpha resulting in increased CXCL1 secretion that fosters
      MPE-associated inflammation. Importantly, IL-1beta-mediated NF-kappaB induction
      in KRAS-mutant tumor cells, as well as their resulting MPE-competence, can only
      be blocked by co-inhibition of both KRAS and IKKalpha, a strategy that overcomes
      drug resistance to individual treatments. Hence we show that mutant KRAS
      facilitates IKKalpha-mediated responsiveness of tumor cells to host IL-1beta,
      thereby establishing a host-to-tumor signaling circuit that culminates in
      inflammatory MPE development and drug resistance.

PMID- 29445183
TI  - Reducing risk and improving maternal perspective-taking and empathy using virtual
      embodiment.
AB  - The ability to perspective-take (cognitive awareness of another's state) and
      empathise (emotional/affective response) are important characteristics for
      sensitive, co-operative and constructive parenting, which assists in developing
      adaptive functioning for children. For the first time, immersive virtual reality
      was used to place parents in the position of a child in order to assess impact on
      perspective-taking and empathy. This novel study was conducted with 20 non-high
      risk Spanish mothers (a pilot study with 12 mothers is reported in supplementary
      files). Mothers were virtually embodied as a 4-year-old child, experienced from
      the first-person perspective and with virtual and real body movements
      synchronised. They interacted with a 'mother avatar', which responded either in a
      Positive or Negative way. Participants reported a strong body ownership illusion
      for the child body that led to cognitive, emotional and physical reactions.
      Experiencing negative maternal behavior increased levels of empathy. In addition,
      the Negative mother led to increased feelings of fear of violence. Physiological
      data indicated greater stress in the Negative than Positive condition. Although
      further research is required to assess the effectiveness of such methods, any
      improvement in empathy that leads to a change in parenting behavior has the
      potential to impact on developmental outcomes for children.

PMID- 29445184
TI  - Parental micronutrient deficiency distorts liver DNA methylation and expression
      of lipid genes associated with a fatty-liver-like phenotype in offspring.
AB  - Micronutrient status of parents can affect long term health of their progeny.
      Around 2 billion humans are affected by chronic micronutrient deficiency. In this
      study we use zebrafish as a model system to examine morphological, molecular and
      epigenetic changes in mature offspring of parents that experienced a one-carbon
      (1-C) micronutrient deficiency. Zebrafish were fed a diet sufficient, or
      marginally deficient in 1-C nutrients (folate, vitamin B12, vitamin B6,
      methionine, choline), and then mated. Offspring livers underwent histological
      examination, RNA sequencing and genome-wide DNA methylation analysis. Parental 1
      C micronutrient deficiency resulted in increased lipid inclusion and we
      identified 686 differentially expressed genes in offspring liver, the majority of
      which were downregulated. Downregulated genes were enriched for functional
      categories related to sterol, steroid and lipid biosynthesis, as well as
      mitochondrial protein synthesis. Differential DNA methylation was found at 2869
      CpG sites, enriched in promoter regions and permutation analyses confirmed the
      association with parental feed. Our data indicate that parental 1-C nutrient
      status can persist as locus specific DNA methylation marks in descendants and
      suggest an effect on lipid utilization and mitochondrial protein translation in
      F1 livers. This points toward parental micronutrients status as an important
      factor for offspring health and welfare.

PMID- 29445186
TI  - Current-induced magnetization switching in atom-thick tungsten engineered
      perpendicular magnetic tunnel junctions with large tunnel magnetoresistance.
AB  - Perpendicular magnetic tunnel junctions based on MgO/CoFeB structures are of
      particular interest for magnetic random-access memories because of their
      excellent thermal stability, scaling potential, and power dissipation. However,
      the major challenge of current-induced switching in the nanopillars with both a
      large tunnel magnetoresistance ratio and a low junction resistance is still to be
      met. Here, we report spin transfer torque switching in nano-scale perpendicular
      magnetic tunnel junctions with a magnetoresistance ratio up to 249% and a
      resistance area product as low as 7.0 Omega um2, which consists of atom-thick W
      layers and double MgO/CoFeB interfaces. The efficient resonant tunnelling
      transmission induced by the atom-thick W layers could contribute to the larger
      magnetoresistance ratio than conventional structures with Ta layers, in addition
      to the robustness of W layers against high-temperature diffusion during
      annealing. The critical switching current density could be lower than 3.0 MA cm-2
      for devices with a 45-nm radius.

PMID- 29445185
TI  - Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association
      with Increased Retinal Renin Expression.
AB  - Diabetic retinopathy (DR) is a leading cause of blindness among working-age
      adults. Increased iron accumulation is associated with several degenerative
      diseases. However, there are no reports on the status of retinal iron or its
      implications in the pathogenesis of DR. In the present study, we found that
      retinas of type-1 and type-2 mouse models of diabetes have increased iron
      accumulation compared to non-diabetic retinas. We found similar iron accumulation
      in postmortem retinal samples from human diabetic patients. Further, we induced
      diabetes in HFE knockout (KO) mice model of genetic iron overload to understand
      the role of iron in the pathogenesis of DR. We found increased neuronal cell
      death, vascular alterations and loss of retinal barrier integrity in diabetic HFE
      KO mice compared to diabetic wildtype mice. Diabetic HFE KO mouse retinas also
      exhibited increased expression of inflammation and oxidative stress markers.
      Severity in the pathogenesis of DR in HFE KO mice was accompanied by increase in
      retinal renin expression mediated by G-protein-coupled succinate receptor GPR91.
      In light of previous reports implicating retinal renin-angiotensin system in DR
      pathogenesis, our results reveal a novel relationship between diabetes, iron and
      renin-angiotensin system, thereby unraveling new therapeutic targets for the
      treatment of DR.

PMID- 29445187
TI  - Adult male mice exposure to nonylphenol alters courtship vocalizations and
      mating.
AB  - The neural circuitry processing male sexual behavior is tightly regulated by
      testosterone and its neural metabolite estradiol. The present study evaluated the
      effects of adult exposure to low doses of nonylphenol (NP), a widespread
      environmental contaminant, on the neuroendocrine regulation of testosterone and
      expression of sexual behavior. Oral exposure of C57BL/6J males to NP (0.5, 5 or
      50 MUg/kg/day) for 4 weeks did not affect circulating levels of testosterone or
      the kisspeptin system, a key regulator of the gonadotropic axis. In contrast,
      mice exposed to NP at 5 MUg/kg/day emitted an increased number and duration of
      ultrasonic vocalizations, took longer to reach ejaculation and showed increased
      number of mounts, intromissions and thrusts. This was associated with normal
      olfactory preference and locomotor activity, and increased anxiety level.
      Analysis of the neural circuitry that underlies sexual behavior showed changes in
      the number of cells expressing androgen and estrogen receptors in males exposed
      to NP at 5 MUg/kg/day. The neural circuitry underlying sexual behavior is thus
      highly sensitive to adult exposure to NP. Furthermore, almost all the observed
      effects were induced at 5 MUg/kg/day of NP, indicating that this endocrine
      disrupter triggers a non-monotonic response in the adult male mouse brain.

PMID- 29445188
TI  - Daily circadian misalignment impairs human cognitive performance task
      dependently.
AB  - Shift work increases the risk for human errors, such that drowsiness due to shift
      work has contributed to major industrial disasters, including Space Shuttle
      Challenger, Chernobyl and Alaska Oil Spill disasters, with extraordinary socio
      economical costs. Overnight operations pose a challenge because our circadian
      biology inhibits cognitive performance at night. Yet how the circadian system
      modulates cognition over multiple days under realistic shift work conditions
      remains to be established. Importantly, because task-specific cognitive brain
      regions show different 24-h circadian dynamics, we hypothesize that circadian
      misalignment impacts cognition task-dependently. Using a biologically-driven
      paradigm mimicking night shift work, with a randomized, cross-over design, we
      show that misalignment between the circadian pacemaker and
      behavioral/environmental cycles increases cognitive vulnerability on sustained
      attention, cognitive throughput, information processing and visual-motor
      performance over multiple days, compared to circadian alignment (day shifts).
      Circadian misalignment effects are task-dependent: while they acutely impair
      sustained attention with recovery after 3-days, they progressively hinder daily
      learning. Individuals felt sleepier during circadian misalignment, but they did
      not rate their performance as worse. Furthermore, circadian misalignment effects
      on sustained attention depended on prior sleep history. Collectively, daily
      circadian misalignment may provide an important biological framework for
      developing countermeasures against adverse cognitive effects in shift workers.

PMID- 29445189
TI  - STK17B promotes carcinogenesis and metastasis via AKT/GSK-3beta/Snail signaling
      in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide with frequent
      intrahepatic and distant metastasis. Elucidating the underlying molecular
      mechanism that modulates HCC progression is critical for exploring novel
      therapeutic strategies. Serine/Threonine Kinase 17B (STK17B) is upregulated in
      HCC tissues, but its role in HCC progression remains elusive. In the present
      studies, we reported that STK17B had a critical role in HCC progression. STK17B
      was significantly upregulated in HCC cell lines and specimens, and patients with
      ectopic STK17B expression characterized with poor clinicopathological features.
      In vitro and in vivo assay demonstrated that inhibition of STK17B markedly
      inhibits HCC tumorigenesis and metastasis, while STK17B overexpression promoted
      these processes. Furthermore, we found that STK17B promoted EMT process via
      activating AKT/GSK-3beta/Snail signal pathway, and miR-455-3p was identified as
      the upstream regulator of STK17B. Combination of high level of STK17B and low
      level of miR-455-3p predicted poor prognosis with higher accuracy for HCC
      patients. In conclusion, our research demonstrated that STK17B promotes HCC
      progression, induces EMT process via activating AKT/GSK-3beta/Snail signal and
      predicts poor prognosis in HCC.

PMID- 29445190
TI  - The chemokine receptor CCR10 promotes inflammation-driven hepatocarcinogenesis
      via PI3K/Akt pathway activation.
AB  - G-protein-coupled receptor (GPCR)-related proteins are dysregulated and the GPCR
      CC-chemokine receptor 10 (CCR10) is significantly upregulated in inflammation
      driven HCC. However, CCR10's role in inflammation-driven hepatocarcinogenesis
      remains unknown. The aim of this study was to evaluate the role of CCR10 in
      inflammation-driven hepatocarcinogenesis. Via a targeted gene expression
      microarray screening alterations in GPCR family gene expression, we found CCR10
      to be significantly upregulated in hepatocytes isolated from inflammation-driven
      human HCC tumors and matching paracancerous tissues. Tetrachloromethane (CCl4)
      induced and diethylnitrosamine (DEN)-induced murine models of inflammatory
      hepatocarcinogenesis displayed significant hepatocellular TNF and CCR10
      upregulation. Exogenous TNF applied to HepG2 and LO2 cell lines as well as wild
      type (WT) mice significantly upregulated hepatocellular CCR10 expression, Akt
      phosphorylation, PCNA expression, and hepatocellular proliferation. Additionally,
      exogenous TNF significantly upregulated secretion of the natural CCR10 ligand
      agonist CCL28 from both cell lines. Transgenic CCR10-knockout (CCR10 KO) in DEN
      treated mice significantly increased hepatocellular apoptosis levels and
      significantly lowered compensatory hepatocellular proliferation but did not
      affect upstream TNF expression. In addition, DEN-treated CCR10 KO mice showed a
      significantly lower liver weight/body weight ratio, significantly lower liver
      tumor incidence, and significantly smaller tumors. Moreover, exogenous CCR10
      expression significantly raised xenograft tumor growth in Balb/c nude mice. In
      vitro, CCR10 transfection or CCL28 treatment in HepG2 and LO2 cell lines
      significantly increased Akt phosphorylation, PCNA expression, and cell
      proliferation, while CCR10 silencing or Akt inhibition produced the opposite
      effects. In vivo, hepatocytes isolated from HCC tumor tissue and matching
      paracancerous tissue in DEN-treated CCR10 KO mice showed significantly lower Akt
      phosphorylation and PCNA expression relative to WT hepatocytes. In conclusion,
      inflammation-induced TNF promotes hepatocellular CCR10 expression and downstream
      PI3K/Akt-mediated hepatocarcinogenesis. CCR10 appears to function as a linkage
      between TNF stimulation and downstream PI3K/Akt pathway activation and shows
      promise as a potential therapeutic target for inflammation-driven HCC.

PMID- 29445191
TI  - Minute hands of clocks indicating the same time are not perceived as haptically
      parallel.
AB  - Many studies have already shown that a large idiosyncratic orientation difference
      is needed to perceive two bars that are far apart as haptically parallel. There
      exist also strong indications that if such bars are imagined to be minute hands
      of clocks, errors made in clock time estimates and clock time settings are much
      smaller. The current study investigated this seemingly discrepancy. Participants
      partook in three experiments: parallel setting, clock time estimate and clock
      time setting, in this order. As the individual parallel settings were used in the
      subsequent clock time estimate experiment, and the estimated clock times in the
      clock time setting experiment, the deviations could be compared directly. In all
      three experiments, the deviations were systematic and idiosyncratic, and
      consistent with a biasing influence of an egocentric reference frame. However,
      the deviations in the two clock time experiments were indeed much smaller than in
      the parallel setting experiment. Task instruction and strengthened focus on an
      allocentric reference frame are the most likely explanations. These findings
      provide fundamental insights in the processing of spatial information. Taking
      these findings into account when designing haptic devices may make these more
      intuitive.

PMID- 29445192
TI  - SPRY2 is a novel MET interactor that regulates metastatic potential and
      differentiation in rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is a predominantly pediatric soft-tissue cancer where the
      tumor cells exhibit characteristics of the developing skeletal muscle, and the
      two most common sub-types are embryonal and alveolar RMS. Elevated activation of
      the receptor tyrosine kinase (RTK) MET is frequent in RMS and is thought to cause
      increased tumor metastasis and lack of differentiation. However, the reasons
      underlying dysregulated MET expression and activation in RMS are not well
      understood. Therefore, we explored the role of Sprouty 2 (SPRY2), a modulator of
      RTK signaling, in regulating MET. We identify SPRY2 as a novel MET interactor
      that colocalizes with and binds MET in both embryonal and alveolar RMS. We find
      that depletion of SPRY2 leads to MET degradation, resulting in reduced migratory
      and clonogenic potential, and induction of differentiation in both embryonal and
      alveolar RMS, outcomes that are identical to depletion of MET. Activation of the
      ERK/MAPK pathway, known to be crucial for regulating cell migration and whose
      inhibition is required for myogenic differentiation, was downregulated upon
      depletion of MET or SPRY2. This provides a direct connection to the decreased
      migration and induction of differentiation upon depletion of MET or SPRY2. Thus,
      these data indicate that SPRY2 interacts with MET and stabilizes it in order to
      maintain signaling downstream of MET, which keeps the ERK/MAPK pathway active,
      resulting in metastatic potential and inhibition of differentiation in RMS. Our
      results identify a novel mechanism by which MET signaling is stabilized in RMS,
      and is a potential target for therapeutic intervention in RMS.

PMID- 29445194
TI  - Spatially-explicit valuation of coastal wetlands for cyclone mitigation in
      Australia and China.
AB  - Coastal wetlands are increasingly recognised for their pivotal role in mitigating
      the growing threats from cyclones (including hurricanes) in a changing climate.
      There is, however, insufficient information about the economic value of coastal
      wetlands for cyclone mitigation, particularly at regional scales. Analysis of
      data from 1990-2012 shows that the variation of cyclone frequencies is related to
      EI Nino strength in the Pacific Ocean adjacent to Australia, but not China. Among
      the cyclones hitting the two countries, there are significant relationships
      between the ratio of total economic damage to gross domestic production (TD/GDP)
      and wetland area within cyclone swaths in Australia, and wetland area plus
      minimum cyclone pressure despite a weak relationship in China. The TD/GDP ratio
      is significantly higher in China than in Australia. Despite their extensive and
      growing occurrence, seawalls in China appear not to play a critical role in
      cyclone mitigation, and cannot replace coastal wetlands, which provide other
      efficient ecosystem services. The economic values of coastal wetlands in
      Australia and China are respectively estimated at US$52.88 billion and 198.67
      billion yr-1 for cyclone mitigation, albeit with large within-country geographic
      variation. This study highlights the urgency to integrate this value into
      existing valuations of coastal wetlands.

PMID- 29445193
TI  - Uncoupling FoxO3A mitochondrial and nuclear functions in cancer cells undergoing
      metabolic stress and chemotherapy.
AB  - While aberrant cancer cell growth is frequently associated with altered
      biochemical metabolism, normal mitochondrial functions are usually preserved and
      necessary for full malignant transformation. The transcription factor FoxO3A is a
      key determinant of cancer cell homeostasis, playing a dual role in survival/death
      response to metabolic stress and cancer therapeutics. We recently described a
      novel mitochondrial arm of the AMPK-FoxO3A axis in normal cells upon nutrient
      shortage. Here, we show that in metabolically stressed cancer cells, FoxO3A is
      recruited to the mitochondria through activation of MEK/ERK and AMPK, which
      phosphorylate serine 12 and 30, respectively, on FoxO3A N-terminal domain.
      Subsequently, FoxO3A is imported and cleaved to reach mitochondrial DNA, where it
      activates expression of the mitochondrial genome to support mitochondrial
      metabolism. Using FoxO3A-/- cancer cells generated with the CRISPR/Cas9 genome
      editing system and reconstituted with FoxO3A mutants being impaired in their
      nuclear or mitochondrial subcellular localization, we show that mitochondrial
      FoxO3A promotes survival in response to metabolic stress. In cancer cells treated
      with chemotherapeutic agents, accumulation of FoxO3A into the mitochondria
      promoted survival in a MEK/ERK-dependent manner, while mitochondrial FoxO3A was
      required for apoptosis induction by metformin. Elucidation of FoxO3A
      mitochondrial vs. nuclear functions in cancer cell homeostasis might help devise
      novel therapeutic strategies to selectively disable FoxO3A prosurvival activity.

PMID- 29445195
TI  - Ultra-high thermal effusivity materials for resonant ambient thermal energy
      harvesting.
AB  - Materials science has made progress in maximizing or minimizing the thermal
      conductivity of materials; however, the thermal effusivity-related to the product
      of conductivity and capacity-has received limited attention, despite its
      importance in the coupling of thermal energy to the environment. Herein, we
      design materials that maximize the thermal effusivity by impregnating copper and
      nickel foams with conformal, chemical-vapor-deposited graphene and octadecane as
      a phase change material. These materials are ideal for ambient energy harvesting
      in the form of what we call thermal resonators to generate persistent electrical
      power from thermal fluctuations over large ranges of frequencies. Theory and
      experiment demonstrate that the harvestable power for these devices is
      proportional to the thermal effusivity of the dominant thermal mass. To
      illustrate, we measure persistent energy harvesting from diurnal frequencies,
      extracting as high as 350 mV and 1.3 mW from approximately 10  degrees C diurnal
      temperature differences.

PMID- 29445196
TI  - On the origins of transport inefficiencies in mesoscopic networks.
AB  - A counter-intuitive behavior analogous to the Braess paradox is encountered in a
      two-terminal mesoscopic network patterned in a two-dimensional electron system
      (2DES). Decreasing locally the electron density of one channel of the network
      paradoxically leads to an increased network electrical conductance. Our low
      temperature scanning gate microscopy experiments reveal different occurrences of
      such puzzling conductance variations, thanks to tip-induced localized
      modifications of electron flow throughout the network's channels in the ballistic
      and coherent regime of transport. The robustness of the puzzling behavior is
      inspected by varying the global 2DES density, magnetic field and the tip-surface
      distance. Depending on the overall 2DES density, we show that either Coulomb
      Blockade resonances due to disorder-induced localized states or Fabry-Perot
      interferences tuned by the tip-induced electrostatic perturbation are at the
      origin of transport inefficiencies in the network, which are lifted when
      gradually closing one channel of the network with the tip.

PMID- 29445197
TI  - Differences in frontotemporal dysfunction during social and non-social cognition
      tasks between patients with autism spectrum disorder and schizophrenia.
AB  - Although literature evidence suggests deficits in social and non-social cognition
      in patients with autistic spectrum disorder (ASD) and schizophrenia (SCZ), the
      difference in neural correlates of the impairments between the two disorders has
      not been elucidated. We examined brain function in response to a non-social
      cognition and a social cognition task using functional near-infrared spectroscopy
      (fNIRS) in 13 patients with ASD, 15 patients with SCZ, and 18 healthy subjects.
      We assessed the brain function of participants using a verbal fluency task and an
      emotional facial recognition task. The patients with ASD showed significantly
      reduced brain activation in the left frontotemporal area during both tasks
      compared to healthy subjects. The patients with ASD with larger score in
      'attention to detail' in the autism spectrum quotient showed lower activation of
      the left frontotemporal area during the two tasks. The patients with SCZ showed
      significantly reduced activation, compared to healthy subjects, and greater
      activation, compared to patients with ASD, in the area during the verbal fluency
      task. The patients with SCZ with more severe symptoms had lower brain activation
      during the task in this area. Our results suggest that two distinct areas are
      involved in the distinctive brain pathophysiology relevant to cognitive
      processing in patients with ASD and SCZ.

PMID- 29445198
TI  - Phase-tuning Metasurface for Circularly Polarized Broadside Radiation in
      Broadband.
AB  - Metasurface antennas (MAs) have been proposed as innovative alternatives to
      conventional bulky configurations for satellite applications because of their low
      profile, low cost, and high gain. The general method of surface impedance
      modulation for designing MAs is complicated, and achieving broad operation
      bandwidth remains a challenge because of its high dispersion response. We propose
      a novel and easy technique to control cylindrical surface waves radiated by a
      phase-tuning metasurface. Simultaneously, this technique exhibits a considerably
      wide working bandwidth. A detailed analysis of the radiation mechanism is
      discussed. A left-hand circularly polarized (LHCP) antenna and a right-hand
      circularly polarized (RHCP) antenna that are based on the phase-tuning
      metasurface are simulated and measured. The measured fractional 3-dB gain
      bandwidth and gain are higher than 17% and 15.57 dBi, respectively, which are
      consistent with the simulated results. Moreover, 30% 3-dB axial ratio is achieved
      for the LHCP and RHCP antennas. To the best knowledge of the authors, it is for
      the first time to realize a circularly polarized broadband MA by using the phase
      tuning mechanism. The approach can be regarded as a new starting point for
      antenna design, thereby paving the way for the development of broadband and low
      profile antennas for future satellite communication.

PMID- 29445199
TI  - Lack of T-bet reduces monocytic interleukin-12 formation and accelerates thrombus
      resolution in deep vein thrombosis.
AB  - The role of leukocytes in deep vein thrombosis (DVT) resolution is incompletely
      understood. We determined how depletion of lysozyme positive (LysM+) cells and a
      switched-off type 1 immune response influences thrombus resolution. DVT was
      induced in 12-week-old male mice by inferior vena cava (IVC) stenosis. Toxin
      mediated depletion of myeloid cells improved thrombus resolution in mice with Cre
      inducible expression of the diphtheria toxin receptor in LysM+ cells. This
      correlated with decreased CD45+ cells, a population shift of Gr-1+ to Gr-1-
      CD11b+ myelomonocytic cells (flow cytometry) and an increase in CC-chemokine
      ligand 2, interleukin-4 and interleukin-10 mRNA expressions. Tbx21-/- mice
      (lacking transcription factor T-bet and marked by an attenuated type 1 immune
      response) with DVT had faster thrombus resolution, a reduction of pro
      inflammatory Ly6Chi monocytes in thrombi and decreased interleukin-12p40 mRNA
      expression than control mice resulting in increased vascular endothelial growth
      factor mRNA expression and improved neovascularization of thrombotic veins.
      Transfer of Tbx21-/- bone marrow into irradiated Tbx21+/+ recipients lead to
      accelerated thrombus resolution with lower T-bet-dependent interleukin-12p40 mRNA
      levels following IVC-stenosis. We conclude that inhibition of Tbet+ interleukin
      12 forming myelomonocytic cells accelerated thrombus resolution. Modulating the
      inflammatory immune response might be an approach to improve therapy of DVT.

PMID- 29445201
TI  - Magnetism and high magnetic-field-induced stability of alloy carbides in Fe-based
      materials.
AB  - Understanding the nature of the magnetic-field-induced precipitation behaviors
      represents a major step forward towards unravelling the real nature of
      interesting phenomena in Fe-based alloys and especially towards solving the key
      materials problem for the development of fusion energy. Experimental results
      indicate that the applied high magnetic field effectively promotes the
      precipitation of M23C6 carbides. We build an integrated method, which breaks
      through the limitations of zero temperature and zero external field, to
      concentrate on the dependence of the stability induced by the magnetic effect,
      excluding the thermal effect. We investigate the intimate relationship between
      the external field and the origins of various magnetics structural
      characteristics, which are derived from the interactions among the various
      Wyckoff sites of iron atoms, antiparallel spin of chromium and Fe-C bond
      distances. The high-magnetic-field-induced exchange coupling increases with the
      strength of the external field, which then causes an increase in the parallel
      magnetic moment. The stability of the alloy carbide M23C6 is more dependent on
      external field effects than thermal effects, whereas that of M2C, M3C and M7C3 is
      mainly determined by thermal effects.

PMID- 29445200
TI  - Impaired beta-arrestin recruitment and reduced desensitization by non-catechol
      agonists of the D1 dopamine receptor.
AB  - Selective activation of dopamine D1 receptors (D1Rs) has been pursued for 40
      years as a therapeutic strategy for neurologic and psychiatric diseases due to
      the fundamental role of D1Rs in motor function, reward processing, and cognition.
      All known D1R-selective agonists are catechols, which are rapidly metabolized and
      desensitize the D1R after prolonged exposure, reducing agonist response. As such,
      drug-like selective D1R agonists have remained elusive. Here we report a novel
      series of selective, potent non-catechol D1R agonists with promising in vivo
      pharmacokinetic properties. These ligands stimulate adenylyl cyclase signaling
      and are efficacious in a rodent model of Parkinson's disease after oral
      administration. They exhibit distinct binding to the D1R orthosteric site and a
      novel functional profile including minimal receptor desensitization, reduced
      recruitment of beta-arrestin, and sustained in vivo efficacy. These results
      reveal a novel class of D1 agonists with favorable drug-like properties, and
      define the molecular basis for catechol-specific recruitment of beta-arrestin to
      D1Rs.

PMID- 29445202
TI  - Chemically induced Fermi level pinning effects of high-k dielectrics on graphene.
AB  - High-k materials such as Al2O3 and HfO2 are widely used as gate dielectrics in
      graphene devices. However, the effective work function values of metal gate in
      graphene FET are significantly deviated from their vacuum work function, which is
      similar to the Fermi level pinning effect observed in silicon MOSFETs with high-k
      dielectric. The degree of deviation represented by a pinning factor was much
      worse with HfO2 (pinning factor (S) = 0.19) than with Al2O3 (S = 0.69). We
      propose that the significant pinning-like behaviors induced by HfO2 are
      correlated with the oxygen exchange reactions occurred at the interface of
      graphene and HfO2.

PMID- 29445203
TI  - Effects of Touch Location and Intensity on Interneurons of the Leech Local Bend
      Network.
AB  - Touch triggers highly precise behavioural responses in the leech. The underlying
      network of this so-called local bend reflex consists of three layers of
      individually characterised neurons. While the population of mechanosensory cells
      provide multiplexed information about the stimulus, not much is known about how
      interneurons process this information. Here, we analyse the responses of two
      local bend interneurons (cell 157 and 159) to a mechanical stimulation of the
      skin and show their response characteristics to naturalistic stimuli.
      Intracellular dye-fills combined with structural imaging revealed that these
      interneurons are synaptically coupled to all three types of mechanosensory cells
      (T, P, and N cells). Since tactile stimulation of the skin evokes spikes in one
      to two cells of each of the latter types, interneurons combine inputs from up to
      six mechanosensory cells. We find that properties of touch location and intensity
      can be estimated reliably and accurately based on the graded interneuron
      responses. Connections to several mechanosensory cell types and specific response
      characteristics of the interneuron types indicate specialised filter and
      integration properties within this small neuronal network, thus providing
      evidence for more complex signal processing than previously thought.

PMID- 29445204
TI  - The effect of air pulse-driven whole eye motion on the association between
      corneal hysteresis and glaucomatous visual field progression.
AB  - Corneal hysteresis (CH) measured with Ocular Response Analyzer (Reichert: ORA)
      has been reported to be closely related to the glaucomatous visual field (VF)
      progression. The air pulse applied to an eye not only induces corneal
      deformation, but also whole eye motion (WEM), which may result in an inaccurate
      measurement of CH. Here we investigated the influence of air pulse-driven WEM
      measured with the Corivs ST (CST(r), OCULUS) on the relationship between CH and
      VF progression in primary open angle-glaucoma patients. Using the CST parameters
      of the maximal WEM displacement (WEM-d) and the time to reach that displacement
      (WEM-t), the eyes were classified into subgroups (WEM-d low- and high-group, and
      WEM-t short- and long-group). For the whole population and all subgroups, the
      optimal linear mixed model to describe mean of total deviation (mTD) progression
      rate with eight reliable VFs was selected from all combinations of seven
      parameters including CH. As a result, optimal models for the mTD progression rate
      included CH in the whole population, the WEM-d low- group and the WEM-t short
      group, but not in the WEM-d high-group and the WEM-t long-group. Our findings
      indicated association between CH and glaucomatous progression can be weakened
      because of large WEM.

PMID- 29445205
TI  - The plasmatic and salivary levels of IL-1beta, IL-18 and IL-6 are associated to
      emotional difference during stress in young male.
AB  - Saliva collection is considered a non-invasive method to detect inflammatory
      markers in response to emotional states within natural social contexts. Numerous
      studies have prompted an important role of cytokines in modulating distinct
      aspects of social and emotional behavior. The aim of this study was to
      investigate the reliability of plasma and saliva as investigative tools for
      measure some inflammatory marker levels (CRP, IL-1beta, IL-18, and IL-6). At the
      same time, the relationships between these markers and emotional states in
      response to a socio-cognitive stress (Academic Exam, AE), were considered. It was
      demonstrated that the plasma and saliva concentrations of all immune-mediators
      analyzed were significantly related across the socio-cognitive stress. In
      addition, when there was a close correlation to AE, the anger state, the IL
      1beta, the IL-18 salivary and plasmatic concentrations were significantly higher,
      while they decreased during the AE. On the other hand, the anxiety state and the
      IL-6 levels significantly increased throughout the AE. The IL-1beta and IL-6 were
      positively associated to the anger and the anxiety state, respectively. In
      conclusion, our data highlight that different immune markers are similarly
      detectable in plasma and saliva during socio-cognitive stress. Also, they could
      be related to different emotional responses.

PMID- 29445206
TI  - Nanostructuring one-dimensional and amorphous lithium peroxide for high round
      trip efficiency in lithium-oxygen batteries.
AB  - The major challenge facing lithium-oxygen batteries is the insulating and bulk
      lithium peroxide discharge product, which causes sluggish decomposition and
      increasing overpotential during recharge. Here, we demonstrate an improved round
      trip efficiency of ~80% by means of a mesoporous carbon electrode, which directs
      the growth of one-dimensional and amorphous lithium peroxide. Morphologically,
      the one-dimensional nanostructures with small volume and high surface show
      improved charge transport and promote delithiation (lithium ion dissolution)
      during recharge and thus plays a critical role in the facile decomposition of
      lithium peroxide. Thermodynamically, density functional calculations reveal that
      disordered geometric arrangements of the surface atoms in the amorphous structure
      lead to weaker binding of the key reaction intermediate lithium superoxide,
      yielding smaller oxygen reduction and evolution overpotentials compared to the
      crystalline surface. This study suggests a strategy to enhance the decomposition
      rate of lithium peroxide by exploiting the size and shape of one-dimensional
      nanostructured lithium peroxide.

PMID- 29445207
TI  - Holographic Traction Force Microscopy.
AB  - Traction Force Microscopy (TFM) computes the forces exerted at the surface of an
      elastic material by measuring induced deformations in volume. It is used to
      determine the pattern of the adhesion forces exerted by cells or by cellular
      assemblies grown onto a soft deformable substrate. Typically, colloidal particles
      are dispersed in the substrate and their displacement is monitored by fluorescent
      microscopy. As with any other fluorescent techniques, the accuracy in measuring a
      particule's position is ultimately limited by the number of evaluated fluorescent
      photons. Here, we present a TFM technique based on the detection of probe
      particle displacements by holographic tracking microscopy. We show that nanometer
      scale resolutions of the particle displacements can be obtained and determine the
      maximum volume fraction of markers in the substrate. We demonstrate the
      feasibility of the technique experimentally and measure the three-dimensional
      force fields exerted by colorectal cancer cells cultivated onto a polyacrylamide
      gel substrate.

PMID- 29445208
TI  - Synergistic effect of nano-Pt and Ni spine for HER in alkaline solution: hydrogen
      spillover from nano-Pt to Ni spine.
AB  - The design of active, stable, and cost-effective electrocatalysts for the H2
      evolution reaction (HER) in alkaline conditions is important for electrochemical
      systems such as the chloro-alkaline process and H2 production. Here we report
      catalysts comprising Pt on Ni single crystalline spines (Pt/Ni-SP) with high
      activity and stability for HER in alkaline solution with proposed mechanism. The
      Pt/Ni-SP catalysts are prepared by dispersing platinum nanoparticles (1.7-3.1 nm)
      on the single-crystalline spines (Ni-SP) of Ni urchin-like particles. The size
      and coverage of Pt nanoparticles on Ni-SP are increased with increases in the Pt
      loading amount. X-ray diffraction, high-resolution transmission electron
      microscopy, X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy
      are performed to observe the structure of the Pt/Ni-SP catalyst. The catalysts
      achieve the mass activity of 1.11 A mg-1(Pt), comparing favorably to Pt/C
      catalysts with the mass activity of 0.33 A mg-1(Pt) at 0.05 V overpotential. The
      Tafel slope of the Pt/Ni-SP catalyst is approximately 30 mV dec-1, similar to
      that of Pt, while Pt/Ni-SP is very stable in alkaline solution, like Ni. The
      synergistic effect of Pt/Ni-SP is ascribed to H spillover from Pt to Ni.

PMID- 29445210
TI  - The Caveats of observing Inter-Trial Phase-Coherence in Cognitive Neuroscience.
AB  - Many studies have now consistently reported that the phase angle of ongoing
      oscillatory activity (measured using EEG/MEG), at time of stimulus presentation
      influences detection when stimuli are near-threshold. However, studies examining
      whether the adjustment of the phase angle of oscillations is under top-down
      attentional control have thus far yielded conflicting results. A possible source
      for the discrepancy could be that the estimation of the phase of ongoing
      oscillations as well as its uniformity across trials could be affected by task
      induced changes in the power of oscillations or concurrent evoked responses. One
      measure, Inter-Trial Phase-Locking (ITPC), or the uniformity of phase angles
      across trials, is particularly vulnerable to these factors. Here, using various
      simulations modelling the common task induced changes in the EEG reported in the
      literature, we demonstrate that apparent changes in Inter-Trial Phase-Locking of
      oscillatory activity can occur independent of any actual change in the phase of
      the ongoing activity.

PMID- 29445209
TI  - 3D microfluidic liver cultures as a physiological preclinical tool for hepatitis
      B virus infection.
AB  - With more than 240 million people infected, hepatitis B virus (HBV) is a major
      health concern. The inability to mimic the complexity of the liver using cell
      lines and regular primary human hepatocyte (PHH) cultures pose significant
      limitations for studying host/pathogen interactions. Here, we describe a 3D
      microfluidic PHH system permissive to HBV infection, which can be maintained for
      at least 40 days. This system enables the recapitulation of all steps of the HBV
      life cycle, including the replication of patient-derived HBV and the maintenance
      of HBV cccDNA. We show that innate immune and cytokine responses following
      infection with HBV mimic those observed in HBV-infected patients, thus allowing
      the dissection of pathways important for immune evasion and validation of
      biomarkers. Additionally, we demonstrate that the co-culture of PHH with other
      non-parenchymal cells enables the identification of the cellular origin of immune
      effectors, thus providing a valuable preclinical platform for HBV research.

PMID- 29445211
TI  - Bronchoscopic fibered confocal fluorescence microscopy for longitudinal in vivo
      assessment of pulmonary fungal infections in free-breathing mice.
AB  - Respiratory diseases, such as pulmonary infections, are an important cause of
      morbidity and mortality worldwide. Preclinical studies often require invasive
      techniques to evaluate the extent of infection. Fibered confocal fluorescence
      microscopy (FCFM) is an emerging optical imaging technique that allows for real
      time detection of fluorescently labeled cells within live animals, thereby
      bridging the gap between in vivo whole-body imaging methods and traditional
      histological examinations. Previously, the use of FCFM in preclinical lung
      research was limited to endpoint observations due to the invasive procedures
      required to access lungs. Here, we introduce a bronchoscopic FCFM approach that
      enabled in vivo visualization and morphological characterisation of fungal cells
      within lungs of mice suffering from pulmonary Aspergillus or Cryptococcus
      infections. The minimally invasive character of this approach allowed
      longitudinal monitoring of infection in free-breathing animals, thereby providing
      both visual and quantitative information on infection progression. Both the
      sensitivity and specificity of this technique were high during advanced stages of
      infection, allowing clear distinction between infected and non-infected animals.
      In conclusion, our study demonstrates the potential of this novel bronchoscopic
      FCFM approach to study pulmonary diseases, which can lead to novel insights in
      disease pathogenesis by allowing longitudinal in vivo microscopic examinations of
      the lungs.

PMID- 29445212
TI  - Archimedes' principle for characterisation of recombinant whole cell
      biocatalysts.
AB  - The ability of whole cells to catalyse multistep reactions, often yielding
      synthetically demanding compounds later used by industrial biotech or pharma,
      makes them an indispensable tool of synthetic chemistry. The complex reaction
      network employed by cellular catalysts and the still only moderate predictive
      power of modelling approaches leaves this tool challenging to engineer.
      Frequently, large libraries of semi-rationally generated variants are sampled in
      high-throughput mode in order to then identify improved catalysts. We present a
      method for space- and time-efficient processing of very large libraries (107) of
      recombinant cellular catalysts, in which the phenotypic characterisation and the
      isolation of positive variants for the entire library is done within one minute
      in a single, highly parallelized operation. Specifically, product formation in
      nanolitre-sized cultivation vessels is sensed and translated into the formation
      of catalase as a reporter protein. Exposure to hydrogen peroxide leads to oxygen
      gas formation and thus to a density shift of the cultivation vessel. Exploiting
      Archimedes' principle, this density shift and the resulting upward buoyancy force
      can be used for batch-wise library sampling. We demonstrate the potential of the
      method for both, screening and selection protocols, and envision a wide
      applicability of the system for biosensor-based assays.

PMID- 29445213
TI  - Wireless Data Transmission at Terahertz Carrier Waves Generated from a Hybrid InP
      Polymer Dual Tunable DBR Laser Photonic Integrated Circuit.
AB  - We report for the first time the successful wavelength stabilization of two
      hybrid integrated InP/Polymer DBR lasers through optical injection. The two
      InP/Polymer DBR lasers are integrated into a photonic integrated circuit,
      providing an ideal source for millimeter and Terahertz wave generation by optical
      heterodyne technique. These lasers offer the widest tuning range of the carrier
      wave demonstrated to date up into the Terahertz range, about 20 nm (2.5 THz) on a
      single photonic integrated circuit. We demonstrate the application of this source
      to generate a carrier wave at 330 GHz to establish a wireless data transmission
      link at a data rate up to 18 Gbit/s. Using a coherent detection scheme we
      increase the sensitivity by more than 10 dB over direct detection.

PMID- 29445214
TI  - RACK1 is indispensable for porcine reproductive and respiratory syndrome virus
      replication and NF-kappaB activation in Marc-145 cells.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) causes porcine
      reproductive and respiratory syndrome (PRRS), which is currently insufficiently
      controlled. RACK1 (receptor of activated protein C kinase 1) was first identified
      as a receptor for protein kinase C, with increasing evidence showing that the
      functionally conserved RACK1 plays important roles in cancer development, NF
      kappaB activation and various virus infections. However, the roles of RACK1
      during PRRSV infection in Marc-145 cells have not been described yet. Here we
      demonstrated that infection of Marc-145 cells with the highly pathogenic PRRSV
      strain YN-1 from our lab led to activation of NF-kappaB and upregulation of RACK1
      expression. The siRNA knockdown of RACK1 inhibited PRRSV replication in Marc-145
      cells, abrogated NF-kappaB activation induced by PRRSV infection and reduced the
      viral titer. Furthermore, knockdown of RACK1 could inhibit an ongoing PRRSV
      infection. We found that RACK1 is highly conserved across different species based
      on the phylogenetic analysis of mRNA and deduced amino acid sequences. Taken
      together, RACK1 plays an indispensable role for PRRSV replication in Marc-145
      cells and NF-kappaB activation. The results would advance our further
      understanding of the molecular mechanisms underlying PRRSV infection in swine and
      indicate RACK1 as a promising potential therapeutic target.

PMID- 29445215
TI  - Origin, evolution, and distribution of the molecular machinery for biosynthesis
      of sialylated lipooligosaccharide structures in Campylobacter coli.
AB  - Campylobacter jejuni and Campylobacter coli are the most common cause of
      bacterial gastroenteritis worldwide. Additionally, C. jejuni is the most common
      bacterial etiological agent in the autoimmune Guillain-Barre syndrome (GBS).
      Ganglioside mimicry by C. jejuni lipooligosaccharide (LOS) is the triggering
      factor of the disease. LOS-associated genes involved in the synthesis and
      transfer of sialic acid (glycosyltranferases belonging to family GT-42) are
      essential in C. jejuni to synthesize ganglioside-like LOS. Despite being isolated
      from GBS patients, scarce genetic evidence supports C. coli role in the disease.
      In this study, through data mining and bioinformatics analysis, C. coli is shown
      to possess a larger GT-42 glycosyltransferase repertoire than C. jejuni. Although
      GT-42 glycosyltransferases are widely distributed in C. coli population, only a
      fraction of C. coli strains (1%) are very likely able to express ganglioside
      mimics. Even though the activity of C. coli specific GT-42 enzymes and their role
      in shaping the bacterial population are yet to be explored, evidence presented
      herein suggest that loss of function of some LOS-associated genes occurred during
      agriculture niche adaptation.

PMID- 29445216
TI  - Evaluation of HER2-specific peptide ligand for its employment as radiolabeled
      imaging probe.
AB  - HER2 transmembrane receptor is an important target in immunotherapy treatment of
      breast and gastroesophageal cancer. Molecular imaging of HER2 expression may
      provide essential prognostic and predictive information concerning disseminated
      cancer and aid in selection of an optimal therapy. Radiolabeled low molecular
      weight peptide ligands are particularly attractive as probes for molecular
      imaging, since they reach and bind to the target and clear from non-target organs
      and blood stream faster than bulky antibodies. In this study, we evaluated a
      potential HER2-imaging probe, an A9 nonapeptide, derived from the trastuzumab-Fab
      portion. Its cellular uptake was investigated by mass spectrometry analysis of
      the cytoplasmic cellular extracts. Moreover, based on in-silico modeling, DTPA
      chelator was conjugated to N-terminus of A9. 111In-labeled A9 demonstrated
      nanomolar affinity to HER2-expressing BT474 cells and favorable biodistribution
      profile in NMRI mice. This study suggests that the peptide A9 represents a good
      lead candidate for development of molecular probe, to be used for imaging
      purposes and for the delivery of cytotoxic agents.

PMID- 29445217
TI  - Nonreciprocal current from electron interactions in noncentrosymmetric crystals:
      roles of time reversal symmetry and dissipation.
AB  - In noncentrosymmetric crystals with broken inversion symmetry [Formula: see
      text], the I-V (I: current, V: voltage) characteristic is generally expected to
      depend on the direction of I, which is known as nonreciprocal response and, for
      example, found in p-n junction. However, it is a highly nontrivial issue in
      translationally invariant systems since the time-reversal symmetry T plays an
      essential role, where the two states at crystal momenta k and -k are connected in
      the band structure. Therefore, it has been considered that the external magnetic
      field (B) or the magnetic order which breaks the T-symmetry is necessary to
      realize the nonreciprocal I-V characteristics, i.e., magnetochiral anisotropy.
      Here we theoretically show that the electron correlation in T-broken multi-band
      systems can induce nonreciprocal I-V characteristics without T-breaking. An
      analog of Onsager's relation shows that nonreciprocal current response without T 
      breaking generally requires two effects: dissipation and interactions. By using
      nonequilibrium Green's functions, we derive general formula of the nonreciprocal
      response for two-band systems with onsite interaction. The formula is applied to
      Rice-Mele model, a representative 1D model with inversion breaking, and some
      candidate materials are discussed. This finding offers a coherent understanding
      of the origin of nonreciprocal I-V characteristics, and will pave a way to design
      it.

PMID- 29445218
TI  - New insights into gelatinization mechanisms of cereal endosperm starches.
AB  - A thorough understanding of starch gelatinization is needed to control starch
      functional properties for food processing and human nutrition. Here, we reveal
      the mechanism of structural disassembly of rice, maize and wheat starch granules
      during thermal transitions in which a Rapid Visco Analyzer (RVA) was used to pre
      heat the starches to certain transition points in the differential scanning
      calorimetry (DSC) heating profiles. This was done to generate sufficient material
      for structural analyses. The results from DSC, Raman, X-ray diffraction and
      scanning electron microscopy (SEM) analyses all showed that at the conclusion
      temperature (Tc) of the DSC endotherm rice starch gelatinization was complete,
      whereas residual structural order remained in maize and wheat starches.
      Gelatinization of wheat and maize starch was complete at a temperature higher
      than Tc in the profile, which we define as the end temperature (Te). We propose
      that Te would be better to define the completion point of starch gelatinization
      than Tc.

PMID- 29445219
TI  - Comparative toxicity of five dispersants to coral larvae.
AB  - Oil spill responders require information on the absolute and relative toxicities
      of chemical dispersants to relevant receptor species to assess their use in spill
      response. However, little toxicity data are available for tropical marine species
      including reef-building corals. In this study, we experimentally assessed the sub
      lethal toxicity of five dispersants to larvae of the coral Acropora millepora
      over three short exposure periods (2, 6 and 24 h) reflecting real-world spill
      response scenario durations. Inhibition of larval settlement increased rapidly
      between 2 and 6 h, and was highest at 24 h: EC50 Corexit EC9500A = 4.0 mg l-1;
      Ardrox 6120 = 4.0 mg l-1; Slickgone LTSW = 2.6 mg L-1; Slickgone NS = 11.1 mg L-1
      and Finasol OSR52 = 3.4 mg L-1. Coral larvae were more sensitive to dispersants
      than most other coral life stages and marine taxa, but the toxic thresholds
      (EC10s) exceeded most realistic environmental dispersant concentrations.
      Estimating toxic threshold values for effects of dispersants on coral should
      benefit the decision-making of oil spill responders by contributing to the
      development of species sensitivity distributions (SSDs) for dispersant toxicity,
      and by informing net environmental benefit assessment (NEBA) for dispersant use.

PMID- 29445220
TI  - Association of admission serum levels of vitamin D, calcium, Phosphate, magnesium
      and parathormone with clinical outcomes in neurosurgical ICU patients.
AB  - To evaluate the association of admission serum levels of 25(OH)D, parathormone
      and the related electrolytes with severity of illness and clinical outcomes in
      neurosurgical critically ill patients, serum levels of 25(OH)D, parathormone,
      calcium, magnesium, and phosphate, along with APACHE II score were measured for
      210 patients upon admission. Mean serum 25(OH)D was 21.1 +/- 7.4 ng/mL. 25(OH)D
      deficiency (less than 20 ng/dL) and elevated serum parathormone level were found
      in 47.6% and 38% of patients respectively. Hypocalcaemia, hypophosphatemia,
      hypomagnesaemia and hypermagnesaemia were found in 29.5%, %63.8, 41.9% and 27.6%
      of patients respectively. The APACHE II score was significantly correlated with
      serum levels of 25(OH)D, parathormone, calcium, and phosphate. Multivariate
      regression analysis adjusted by other risk factors showed that among all clinical
      outcomes, admission hypovitaminosis D was associated with longer duration of ICU
      stay and a high admission of parathormone was associated with in ICU mortality.
      We concluded that disorders of admission serum levels of 25(OH)D, parathormone,
      calcium, magnesium, and phosphate are related to the presence of multiple causal
      factors such as severity of disease and are not independently associated with
      clinical outcomes. Most often they are normalize spontaneously with resolution of
      the disease process.

PMID- 29445221
TI  - Remodeling of the Actin/Spectrin Membrane-associated Periodic Skeleton, Growth
      Cone Collapse and F-Actin Decrease during Axonal Degeneration.
AB  - Axonal degeneration occurs in the developing nervous system for the appropriate
      establishment of mature circuits, and is also a hallmark of diverse
      neurodegenerative diseases. Despite recent interest in the field, little is known
      about the changes (and possible role) of the cytoskeleton during axonal
      degeneration. We studied the actin cytoskeleton in an in vitro model of
      developmental pruning induced by trophic factor withdrawal (TFW). We found that F
      actin decrease and growth cone collapse (GCC) occur early after TFW; however,
      treatments that prevent axonal fragmentation failed to prevent GCC, suggesting
      independent pathways. Using super-resolution (STED) microscopy we found that the
      axonal actin/spectrin membrane-associated periodic skeleton (MPS) abundance and
      organization drop shortly after deprivation, remaining low until fragmentation.
      Fragmented axons lack MPS (while maintaining microtubules) and acute
      pharmacological treatments that stabilize actin filaments prevent MPS loss and
      protect from axonal fragmentation, suggesting that MPS destruction is required
      for axon fragmentation to proceed.

PMID- 29445222
TI  - Water Droplet Dynamics on a Hydrophobic Surface in Relation to the Self-Cleaning
      of Environmental Dust.
AB  - The dynamic motion of a water droplet on an inclined hydrophobic surface is
      analyzed with and without environmental dust particles on the surface. Solution
      crystallization of a polycarbonate surface is carried out to generate a
      hydrophobic surface with hierarchical texture composed of micro/nanosize
      spheroids and fibrils. Functionalized nanosize silica particles are deposited on
      the textured surface to reduce contact angle hysteresis. Environmental dust
      particles are collected and characterized using analytical tools prior to the
      experiments. The droplet motion on the hydrophobic surface is assessed using high
      speed camera data, and then, the motion characteristics are compared with the
      corresponding analytical results. The influence of dust particles on the water
      droplet motion and the amount of dust particles picked up from the hydrophobic
      surface by the moving droplet is evaluated experimentally. A 40 MUL droplet was
      observed to roll on the hydrophobic surface with and without dust particles, and
      the droplet slip velocity was lower than the rotational velocity. The rolling
      droplet removes almost all dust particles from the surface, and the mechanism for
      the removal of dust particles from the surface was determined to be water
      cloaking of the dust particles.

PMID- 29445223
TI  - Thermodynamically induced in Situ and Tunable Cu Plasmonic Behaviour.
AB  - The Cu nanoparticles (Cu NPs) were grown in soda-lime glass matrix through Cu+ <
      > Na+ ion exchange methods under thermal annealing in an open environment and
      studied variation in their size on tunable plasmonic behaviour, optical
      absorption spectra and photoluminescence (PL). A blue shift from 570 to 560 nm
      was observed in localized surface plasmon resonance (SPR) of Cu NPs from 550 to
      650  degrees C. A mutual relation between size and surface plasmon resonance with
      full width half maxima (FWHM) has been derived for plasmonic properties at
      variable temperatures. Structural investigations of embedded Cu NPs have been
      confirmed by using HRTEM and EDX. Grazing incidence X-ray diffraction (GIXRD) had
      identified a crystalline nature of Cu NPs under annealed conditions. XPS, Raman
      and secondary ion mass spectroscopies (SIMS) have identified an embedding
      behaviour of Cu NPs in glass matrix. Plasmonic and thermodynamic properties of
      embedded Cu NPs have explained their in situ thermal growth mechanism for
      efficient distribution where enthalpy (?H), entropy (?S) and Gibbs free energy
      (?G) have interpreted their temperature driven Cu NPs growth. An interdependence
      of ?H, ?S and ?G has been developed vis-a-vis activation energy on an extent of
      12.54 J/mol.

PMID- 29445224
TI  - Lup-20(29)-en-3beta,28-di-yl-nitrooxy acetate affects MCF-7 proliferation through
      the crosstalk between apoptosis and autophagy in mitochondria.
AB  - Betulin (BT), a pentacyclic lupine-type triterpenoid natural product, possesses
      antitumor activity in various types of cancers. However, its clinical development
      was discouraged due to its low biological activities and poor solubility. We
      prepared lup-20(29)-en-3beta,28-di-yl-nitrooxy acetate (NBT), a derivative of BT,
      that was chemically modified at position 3 of ring A and C-28 by introducing a NO
      releasing moiety. This study mainly explored the mechanism of NBT in treating
      breast cancer through the crosstalk between apoptosis and autophagy in
      mitochondria. NBT possessed a potent antiproliferative activity in MCF-7 cells
      both in vitro and in vivo. Mechanically, NBT affected cell death through the
      mitochondrial apoptosis pathway and autophagy. NBT induced cell cycle arrest in
      the G0/G1 phase by decreasing the expression of cyclin D1. It also induced
      mitochondrial apoptosis by increasing the expression of Bax, caspase-9, and
      poly(ADP-ribose) polymerase and mitochondrial membrane potential loss and leaks
      of cytochrome c (Cyt C) from mitochondria in MCF-7 cells and decreasing the
      expression of mitochondrial Bcl-2. We further demonstrated whether chloroquine
      (CQ), which inhibits the degradation of autophagosome induced by NBT, affects the
      proliferation of MCF-7 cells compared with NBT. The experiments inferred that the
      combination of NBT and CQ significantly promoted MCF-7 cell mitochondria to
      divide and Cyt C to be released from mitochondria to the cytoplasm, resulting in
      an increased apoptosis rate. The in vivo experiments showed that NBT inhibited
      the growth of MCF-7 tumor via the apoptosis pathway, and its effect was similar
      to 5-fluorouracil.

PMID- 29445225
TI  - Atrial Fibrillation Characteristics in Patients on Haemodialysis vs. Peritoneal
      Dialysis.
AB  - Atrial fibrillation (AF) is highly prevalent in dialysis patients, however
      whether its impact differs between patients on haemodialysis (HD) vs. peritoneal
      dialysis (PD) is unknown. We aimed to compare the association of AF and clinical
      outcomes in different dialysis modalities. We performed a population based
      retrospective cohort study, including adult patients who initiated dialysis
      between the years 2002 and 2015. Clinical, echocardiographic and laboratory data
      were reviewed and correlated with outcomes in HD vs. PD. During the study period,
      1,130 patients began dialysis. Of the 997 patients without AF before dialysis
      initiation, 17% developed new-onset AF after the initiation of dialysis (17.3% of
      HD vs. 13.7% of PD patients, p = 0.27). Using multivariate analysis, only
      enlarged left atrium at dialysis initiation (hazard ratio (HR) 2.82, CI95% 2.00
      3.99) and age (HR 1.04, CI95% 1.03-1.06) were significantly associated with AF.
      Dialysis modality was not a significant predictor of AF in either univariate or
      multivariate analysis. In conclusion, our study demonstrated that AF is common in
      dialysis patients irrespective of modality. In our cohort, the risk factors
      associated with AF were older age and enlarged left atrium. AF was associated
      with increased rates of heart failure and mortality, but not stroke.

PMID- 29445226
TI  - GCY-35/GCY-36-TAX-2/TAX-4 Signalling in O2 Sensory Neurons Mediates Acute
      Functional Ethanol Tolerance in Caenorhabditis elegans.
AB  - Ethanol is a widely used beverage and abused drug. Alcoholism causes severe
      damage to human health and creates serious social problems. Understanding the
      mechanisms underlying ethanol actions is important for the development of
      effective therapies. Alcohol has a wide spectrum of effects on physiological
      activities and behaviours, from sensitization to sedation and even intoxication
      with increasing concentrations. Animals develop tolerance to ethanol. However,
      the underlying mechanisms are not well understood. In Caenorhabditis elegans, NPR
      1 negatively regulates the development of acute tolerance to ethanol. Here, using
      in vivo Ca2+ imaging, behavioural tests and chemogenetic manipulation, we show
      that the soluble guanylate cyclase complex GCY-35/GCY-36-TAX-2/TAX-4 signalling
      pathway in O2 sensory neurons positively regulates acute functional tolerance in
      npr-1 worms.

PMID- 29445227
TI  - Novel ubiquitin-independent nucleolar c-Myc degradation pathway mediated by
      antizyme 2.
AB  - The proto-oncogene c-Myc encodes a short-lived protein c-Myc that regulates
      various cellular processes including cell growth, differentiation and apoptosis.
      Degradation of c-Myc is catalyzed by the proteasome and requires phosphorylation
      of Thr-58 for ubiquitination by E3 ubiquitin ligase, Fbxw7/ FBW7. Here we show
      that a polyamine regulatory protein, antizyme 2 (AZ2), interacts with c-Myc in
      the nucleus and nucleolus, to accelerate proteasome-mediated c-Myc degradation
      without ubiquitination or Thr-58 phosphorylation. Polyamines, the inducer of AZ2,
      also destabilize c-Myc in an AZ2-dependent manner. Knockdown of AZ2 by small
      interfering RNA (siRNA) increases nucleolar c-Myc and also cellular pre-rRNA
      whose synthesis is promoted by c-Myc. AZ2-dependent c-Myc degradation likely
      operates under specific conditions such as glucose deprivation or hypoxia. These
      findings reveal the targeting mechanism for nucleolar ubiquitin-independent c-Myc
      degradation.

PMID- 29445228
TI  - A Study on Curing Kinetics of Nano-Phase Modified Epoxy Resin.
AB  - In this paper, DSC curves at different heating rates were measured by DSC, the
      characteristic curing temperature was determined, and the optimum curing
      conditions were obtained. The KAS method, Friedman method and FWO method were
      used to analyze the DSC curves respectively. The kinetic parameters and the
      reaction mechanism function of the curing system were obtained, and the results
      of different analytical methods were compared and analyzed. Result from fitting
      and verification of the curing kinetic model for the curing system of the nano
      phase modified epoxy resin further demonstrates that the nano-particle could play
      a catalytic role in the curing reaction of the epoxy resin and could reduce the
      apparent activation energy of the system, thus it is considered as a breakthrough
      in the field of resin research.

PMID- 29445229
TI  - Enhanced Electrochemical Properties of Zr4+-doped Li1.20[Mn0.52Ni0.20Co0.08]O2
      Cathode Material for Lithium-ion Battery at Elevated Temperature.
AB  - The typical co-precipitation method was adopted to synthesized the Li-excess
      Li1.20[Mn0.52-xZr x Ni0.20Co0.08]O2 (x = 0, 0.01, 0.02, 0.03) series cathode
      materials. The influences of Zr4+ doping modification on the microstructure and
      micromorphology of Li1.20[Mn0.52Ni0.20Co0.08]O2 cathode materials were studied
      intensively by the combinations of XRD, SEM, LPS and XPS. Besides, after the
      doping modification with zirconium ions, Li1.20[Mn0.52Ni0.20Co0.08]O2 cathode
      demonstrated the lower cation mixing, superior cycling performance and higher
      rate capacities. Among the four cathode materials, the
      Li1.20[Mn0.50Zr0.02Ni0.20Co0.08]O2 exhibited the prime electrochemical properties
      with a capacity retention of 88.7% (201.0 mAh g-1) after 100 cycles at 45 
      degrees C and a discharge capacity of 114.7 mAh g-1 at 2 C rate. The EIS results
      showed that the Zr4+ doping modification can relieve the thickening of SEI films
      on the surface of cathode and accelerate the Li+ diffusion rate during the charge
      and discharge process.

PMID- 29445230
TI  - Investigation of biomarkers alterations after an acute tissue trauma in human
      trapezius muscle, using microdialysis.
AB  - Alterations in muscle milieu are suggested as important activity of peripheral
      drive in patients with chronic musculoskeletal pain (CMP). Microdialysis (MD) has
      been used in monitoring altered metabolic response pattern in muscles. However,
      the insertion of MD probe causes a local tissue trauma. Whether and how
      metabolites in trapezius muscle are affected by acute tissue trauma is unknown.
      Hence, this study investigated the metabolic response and nociceptive reaction of
      the tissue following MD probe insertion in patients with CMP and healthy
      individuals. Fifty-nine patients and forty pain-free volunteers were recruited.
      Pressure pain thresholds (PPTs) were obtained at the trapezius and tibialis
      muscles. Pain questionnaires determined the levels of pain related aspects. MD
      (20 kDa cut-off) was performed in the trapezius and samples were collected within
      40 min. Interstitial concentration of the metabolites was analyzed by a two-way
      mixed-ANOVA. The metabolic response pattern changed over time and alterations in
      the level of metabolites could be seen in both CMP and healthy controls. Pain
      questionnaires and pain intensities manifested clinical aspects of pain closely
      to what CMP patients describe. Analyzing metabolites due to acute tissue trauma
      by aid of MD may be a useful model to investigate altered metabolic response
      effect in CMP.

PMID- 29445231
TI  - Impact of nanoparticles on the Bacillus subtilis (3610) competence.
AB  - Due to the physicochemical properties of nanoparticles, the use of nanomaterials
      increases every year in industrial and medical processes. At the same time, the
      increasing number of bacteria becoming resistant to many antibiotics, mostly by a
      horizontal gene transfer process, is a major public health concern. We herein
      report, for the first time, the role of nanoparticles in the physiological
      induction of horizontal gene transfer in bacteria. Besides the most well-known
      impacts of nanoparticles on bacteria, i.e. death or oxidative stress, two
      nanoparticles, n-ZnO and n-TiO2, significantly and oppositely impact the
      transformation efficiency of Bacillus subtilis in biofilm growth conditions, by
      modification of the physiological processes involved in the induction of
      competence, the first step of transformation. This effect is the consequence of a
      physiological adaptation rather than a physical cell injury: two oligopeptide ABC
      transporters, OppABCDF and AppDFABC, are differentially expressed in response to
      nanoparticles. Interestingly, a third tested nanoparticle, n-Ag, has no
      significant effect on competence in our experimental conditions. Overall, these
      results show that nanoparticles, by altering bacterial physiology and especially
      competence, may have profound influences in unsuspected areas, such as the
      dissemination of antibiotic resistance in bacteria.

PMID- 29445232
TI  - The Cerebellum of Patients with Steatohepatitis Shows Lymphocyte Infiltration,
      Microglial Activation and Loss of Purkinje and Granular Neurons.
AB  - Peripheral inflammation contributes to minimal hepatic encephalopathy in chronic
      liver diseases, which could be mediated by neuroinflammation. Neuroinflammation
      in cerebellum of patients with chronic liver diseases has not been studied in
      detail. Our aim was to analyze in cerebellum of patients with different grades of
      liver disease, from mild steatohepatitis to cirrhosis and hepatic encephalopathy:
      (a) neuronal density in Purkinje and granular layers; (b) microglial activation;
      (c) astrocyte activation; (d) peripheral lymphocytes infiltration; (e) subtypes
      of lymphocytes infiltrated. Steatohepatitis was classified as SH1, SH2 and SH3.
      Patients with SH1 show Th17 and Tfh lymphocytes infiltration in the meninges,
      microglia activation in the molecular layer and loss of 16 +/- 4% of Purkinje and
      19 +/- 2% of granular neurons. White matter remains unaffected. With the
      progression of liver disease to worse stages (SH2, SH3, cirrhosis) activation of
      microglia and astrocytes extends to white matter, Bergman glia is damaged in the
      molecular layer and there is a further loss of Purkinje neurons. The results
      reported show that neuroinflammation in cerebellum occurs at early stages of
      liver disease, even before reaching cirrhosis. Neuroinflammation occurs earlier
      in the molecular layer than in white matter, and is associated with infiltration
      of peripheral Th17 and Tfh lymphocytes.

PMID- 29445233
TI  - In vitro cytotoxicity activity of novel Schiff base ligand-lanthanide complexes.
AB  - A Schiff base ligand (SBL), N2, N3-bis (anthracen-9-ylmethylene) pyridine-2, 3
      diamine, was synthesized through the condensation of 2,6-diaminopyridine and
      anthracene-9-carbaldehyde using a 1:2 ratio. 1H NMR spectra confirmed the
      observation of non-involvement aromatic carboxylic proton in SBL. A novel series
      of lanthanide (i.e., praseodymium (Pr), erbium (Er), and ytterbium (Yb))-based
      SBL metal complexes was successfully synthesized, and their functional groups
      were elaborately demonstrated using UV-visible, Fourier transform infrared (FT
      IR), and fluorescence spectroscopy analyses. FT-IR spectral studies revealed that
      SBL behaved as a bidentate ligand and it was structured with metal ions by the
      two azomethine nitrogens. The synthesized SBL-based metal complexes were
      elaborately performed for cytotoxicity activity versus Vero, human breast cancer
      (MCF7), and cervical (HeLa) anticancer cell lines.

PMID- 29445234
TI  - Tuning the Optical Properties of Silicon Quantum Dots via Surface
      Functionalization with Conjugated Aromatic Fluorophores.
AB  - Silicon Quantum Dots (SQDs) have recently attracted great interest due to their
      excellent optical properties, low cytotoxicity, and ease of surface modification.
      The size of SQDs and type of ligand on their surface has a great influence on
      their optical properties which is still poorly understood. Here we report the
      synthesis and spectroscopic studies of three families of unreported SQDs
      functionalized by covalently linking to the aromatic fluorophores, 9
      vinylphenanthrene, 1-vinylpyrene, and 3-vinylperylene. The results showed that
      the prepared functionalized SQDs had a highly-controlled diameter by HR-TEM,
      ranging from 1.7-2.1 nm. The photophysical measurements of the assemblies
      provided clear evidence for efficient energy transfer from the fluorophore to the
      SQD core. Forster energy transfer is the likely mechanism in these assemblies. As
      a result of the photogenerated energy transfer process, the emission color of the
      SQD core could be efficiently tuned and its emission quantum efficiency enhanced.
      To demonstrate the potential application of the synthesized SQDs for bioimaging
      of cancer cells, the water-soluble perylene- and pyrene-capped SQDs were examined
      for fluorescent imaging of HeLa cells. The SQDs were shown to be of low
      cytotoxicity.

PMID- 29445235
TI  - Development and application of a rapid Mycobacterium tuberculosis detection
      technique using polymerase spiral reaction.
AB  - Mycobacterium tuberculosis is an age-old bacterium that is difficult to
      eliminate. A simple and rapid diagnostic method is of great importance to prevent
      the spread of M. tuberculosis. Here, we developed a low-cost rapid M.
      tuberculosis nucleic acid detection technique, named GenePop, which enabled the
      storage and transport of M. tuberculosis diagnostic reagent at ambient
      temperatures, without the need for professional operations or expensive
      instrumentation. Using a vitrification method, we vitrified heat-unstable
      components onto the cap of a reaction tube, and placed heat-stable components at
      the bottom of the reaction tube by sealing them with paraffin wax. The all-in-one
      detection tube, when used together with our other invention-a multi-functional
      sample treatment tube pre-filled with a nucleic acid-releasing agent-only
      required three simple steps to yield results. A comparative analysis with a
      commercial qPCR kit for M. tuberculosis indicated that our new technique had a
      concordance rate of 91.6%, showing no cross-reactivity with 11 other bacteria.
      The complete operation time was only 65 min. It is suitable for use in field
      settings or by personnel in grass-root units, and is applicable in household
      activities, hence can be used in developing countries.

PMID- 29445237
TI  - Comparing watershed afforestation and natural revegetation impacts on soil
      moisture in the semiarid Loess Plateau of China.
AB  - Two contiguous watersheds in the Loess Plateau in China that differed in the way
      their vegetation had been restored-afforestation or natural revegetation-differed
      in their consumption of soil moisture: the afforested watershed consumed more
      soil moisture, although the difference was significant only in wet years. Yet,
      both the afforestation and natural revegetation did not induce the soil
      desiccation in the study area. In the afforested watershed, soil moisture was
      depleted even beyond a depth of 100 cm, whereas in the grassland (natural
      revegetation), the depletion was confined to a layer less than 60 cm deep.
      Rainfall in the growing season accounted for 46-60% of the variation in soil
      moisture in the 0-60 cm layer in the grassland, but only 22-39% of that in the
      forest land. Overall, afforestation is the better option for the Loess Plateau
      only in areas where the annual rainfall is more than 500 mm. In any attempt at
      revegetation, the choice of tree species and planting densities should match the
      carrying capacity of the region's water resources.

PMID- 29445236
TI  - Retinotopic effects of visual attention revealed by dichoptic multifocal
      pupillography.
AB  - Multifocal pupillographic objective perimetry (mfPOP) has recently been shown to
      be able to measure cortical function. Here we assessed 44 regions of the central
      60 degrees of the visual fields of each eye concurrently in 7 minutes/test. We
      examined how foveally- and peripherally-directed attention changed response
      sensitivity and delay across the 44 visual field locations/eye. Four experiments
      were completed comparing white, yellow and blue stimulus arrays. Experiments 1 to
      4 tested 16, 23, 9 and 6 subjects, 49/54 being unique. Experiment 1, Experiments
      2 and 3, and Experiment 4 used three variants of the mfPOP method that provided
      increasingly improved signal quality. Experiments 1 to 3 examined centrally
      directed attention, and Experiment 4 compared effects of attention directed to
      different peripheral targets. Attention reduced the sensitivity of the peripheral
      locations in Experiment 1, but only for the white stimuli not yellow. Experiment
      2 confirmed that result. Experiment 3 showed that blue stimuli behaved like
      white. Peripheral attention showed increased sensitivity around the attentional
      targets. The results are discussed in terms of the cortical inputs to the
      pupillary system. The results agree with those from multifocal and other fMRI and
      VEP studies. mfPOP may be a useful adjunct to those methods.

PMID- 29445238
TI  - VPS35 depletion does not impair presynaptic structure and function.
AB  - The endosomal system is proposed as a mediator of synaptic vesicle recycling, but
      the molecular recycling mechanism remains largely unknown. Retromer is a key
      protein complex which mediates endosomal recycling in eukaryotic cells, including
      neurons. Retromer is important for brain function and mutations in retromer genes
      are linked to neurodegenerative diseases. In this study, we aimed to determine
      the role of retromer in presynaptic structure and function. We assessed the role
      of retromer by knocking down VPS35, the core subunit of retromer, in primary
      hippocampal mouse neurons. VPS35 depletion led to retromer dysfunction, measured
      as a decrease in GluA1 at the plasma membrane, and bypassed morphological defects
      previously described in chronic retromer depletion models. We found that retromer
      is localized at the mammalian presynaptic terminal. However, VPS35 depletion did
      not alter the presynaptic ultrastructure, synaptic vesicle release or retrieval.
      Hence, we conclude that retromer is present in the presynaptic terminal but it is
      not essential for the synaptic vesicle cycle. Nonetheless, the presynaptic
      localization of VPS35 suggests that retromer-dependent endosome sorting could
      take place for other presynaptic cargo.

PMID- 29445240
TI  - High fat diet-induced metabolically obese and normal weight rabbit model shows
      early vascular dysfunction: mechanisms involved.
AB  - BACKGROUND: Obesity contributes significantly to the development and evolution of
      cardiovascular disease (CVD) which is believed to be mediated by oxidative
      stress, inflammation and endothelial dysfunction. However, the vascular health of
      metabolically obese and normal weight (MONW) individuals is not completely
      comprehended. OBJECTIVES: The purpose of our study was to evaluate vascular
      function on the basis of a high fat diet (HFD)-MONW rabbit model. SUBJECTS:
      Twenty four male rabbits were randomly assigned to receive either a regular diet
      (CD, n = 12) or a high-fat diet (18% extra fat on the regular diet, HFD, n = 12)
      for 6 weeks. RESULTS: Body weight, TBARS and gluthathione serum levels were
      similar between the groups; fasting glucose, triglycerides, C reactive protein
      (CRP), visceral adipose tissue (VAT), triglyceride-glucose index (TyG index) were
      higher in the HFD group. Compared to CD, the HFD rabbits had glucose intolerance
      and lower HDL-cholesterol and plasma nitrites levels. Thoracic aortic rings from
      HFD rabbits exhibited: (a) a reduced acetylcholine-induced vasorelaxation; (b) a
      greater contractile response to norepinephrine and KCl; (c) an improved
      angiotensin II-sensibility. The HFD-effect on acetylcholine-response was reversed
      by the cyclooxygenase-2 (COX-2) inhibitor (NS398) and the cyclooxygenase-1
      inhibitor (SC560), and the HFD-effect on angiotensin II was reversed by NS398 and
      the TP receptor blocker (SQ29538). Immunohistochemistry and western blot studies
      showed COX-2 expression only in arteries from HFD rabbits. CONCLUSIONS: Our study
      shows a positive pro-inflammatory status of HFD-induced MONW characterized by
      raised COX-2 expression, increase of the CRP levels, reduction of NO release and
      oxidative stress-controlled conditions in an early stage of metabolic alterations
      characteristic of metabolic syndrome. Endothelial dysfunction and increased
      vascular reactivity in MONW individuals may be biomarkers of early vascular
      injury. Therefore, the metabolic changes induced by HFD even in normal weight
      individuals may be associated to functional alterations of blood vessels.

PMID- 29445239
TI  - The Urokinase Receptor Induces a Mesenchymal Gene Expression Signature in
      Glioblastoma Cells and Promotes Tumor Cell Survival in Neurospheres.
AB  - PLAUR encodes the urokinase receptor (uPAR), which promotes cell survival,
      migration, and resistance to targeted cancer therapeutics in glioblastoma cells
      in culture and in mouse model systems. Herein, we show that patient survival
      correlates inversely with PLAUR mRNA expression in gliomas of all grades, in
      glioblastomas, and in the subset of glioblastomas that demonstrate the
      mesenchymal gene expression signature. PLAUR clusters with genes that define the
      more aggressive mesenchymal subtype in transcriptome profiles of glioblastoma
      tissue and glioblastoma cells in neurospheres, which are enriched for multipotent
      cells with stem cell-like qualities. When PLAUR was over-expressed or silenced in
      glioblastoma cells, neurosphere growth and expression of mesenchymal subtype
      biomarkers correlated with uPAR abundance. uPAR also promoted glioblastoma cell
      survival in neurospheres. Constitutively-active EGF Receptor (EGFRvIII) promoted
      neurosphere growth; however, unlike uPAR, EGFRvIII did not induce the mesenchymal
      gene expression signature. Immunohistochemical analysis of human glioblastomas
      showed that uPAR is typically expressed by a small sub-population of the cancer
      cells; it is thus reasonable to conclude that this subpopulation of cells is
      responsible for the effects of PLAUR on patient survival. We propose that uPAR
      expressing glioblastoma cells demonstrate a mesenchymal gene signature, an
      increased capacity for cell survival, and stem cell-like properties.

PMID- 29445241
TI  - Is early life exposure to polyomaviruses and herpesviruses associated with
      obesity indices and metabolic traits in childhood?
AB  - BACKGROUND: Evidence for an infectious origin of obesity is emerging. We explored
      whether common viruses were associated with obesity and metabolic traits.
      METHODS: We used cross-sectional (n = 674) and prospective (n = 440) data from
      children participating at the 4 and 6 years of age follow-up in the Rhea birth
      cohort. Presence of IgG antibodies to ten polyomaviruses (BKPyV, JCPyV, KIPyV,
      WUPyV, HPyV6, HPyV7, TSPyV, MCPyV, HPyV9, and HPyV10) and four herpesviruses
      (EBV, CMV, HSV-1, and HSV-2) were measured at age 4. Body mass index, waist
      circumference, and skinfold thickness were measured at age 4 and 6. Data on serum
      lipids, leptin, and adiponectin were also available. Multivariable linear
      regression models were used to explore the associations. RESULTS: At 4 years of
      age, seroprevalence to polyomaviruses ranged from 21.0% for HPyV9 to 82.0% for
      HPyV10. Seroprevalence for EBV, CMV, HSV-1, and HSV-2 was 53.0%, 26.0%, 3.6%, and
      1.5% respectively. BKPyV seropositivity was associated with lower BMI SD score at
      age 4 [-0.21 (95% CI: -0.39, -0.03)] and 6 [-0.27 (95% CI:-0.48, -0.05)], waist
      circumference at age 4 [-1.12 cm (95% CI: -2.10, -0.15)] and 6 [-1.73 cm (95% CI:
      -3.33, -0.12)], sum of four skinfolds [-2.97 mm (95% CI: -5.70, -0.24)], and
      leptin levels at age 4 [ratio of geometric means, 0.83 (95% CI: 0.70, 0.98)]. CMV
      seropositivity was associated with higher BMI SD score at age 4 [0.28 (95% CI:
      0.11, 0.45)] and 6 [0.24 (95% CI: 0.03, 0.45)] and sum of four skinfolds at age 6
      [4.75 mm (95% CI: 0.67, 8.83)]. Having "2-3 herpesviruses infections" (versus "0
      herpesvirus infections") was associated with higher BMI SD score [0.32, (95% CI:
      0.12, 0.53)], waist circumference [1.22 cm (95% CI: 0.13, 2.31)], and sum of four
      skinfolds [3.26 mm (95% CI: 0.18, 6.35)] at age 4. Polyomaviruses burden was not
      associated with outcomes. CONCLUSIONS: A higher herpesviruses burden and CMV
      seropositivity were associated with obesity traits in childhood.

PMID- 29445242
TI  - Colorectal Cancer-Associated Genes Are Associated with Tooth Agenesis and May
      Have a Role in Tooth Development.
AB  - Previously reported co-occurrence of colorectal cancer (CRC) and tooth agenesis
      (TA) and the overlap in disease-associated gene variants suggest involvement of
      similar molecular pathways. Here, we took an unbiased approach and tested genome
      wide significant CRC-associated variants for association with isolated TA. Thirty
      single nucleotide variants (SNVs) in CRC-predisposing genes/loci were genotyped
      in a discovery dataset composed of 440 individuals with and without isolated TA.
      Genome-wide significant associations were found between TA and ATF1 rs11169552 (P
      = 4.36 * 10-10) and DUSP10 rs6687758 (P = 1.25 * 10-9), and positive association
      found with CASC8 rs10505477 (P = 8.2 * 10-5). Additional CRC marker haplotypes
      were also significantly associated with TA. Genotyping an independent dataset
      consisting of 52 cases with TA and 427 controls confirmed the association with
      CASC8. Atf1 and Dusp10 expression was detected in the mouse developing teeth from
      early bud stages to the formation of the complete tooth, suggesting a potential
      role for these genes and their encoded proteins in tooth development. While their
      individual contributions in tooth development remain to be elucidated, these
      genes may be considered candidates to be tested in additional populations.

PMID- 29445243
TI  - Quantitative assessment of liver fibrosis (qFibrosis) reveals precise outcomes in
      Ishak "stable" patients on anti-HBV therapy.
AB  - Current widely used semiquantitative histological assessment methods are
      insensitive to identify subtle changes of liver fibrosis. Therefore, to precisely
      assess therapeutic efficacy on chronic hepatitis B (CHB), we explored the utility
      of qFibrosis (a fully-quantitative morphometric method employing second harmonic
      generation/two photon excitation fluorescence) in liver fibrosis evaluation.
      Fibrosis changes were evaluated by Ishak fibrosis scoring and qFibrosis in CHB
      patients with paired liver biopsies before and after 78 weeks' antiviral therapy.
      A total of 162 patients with qualified paired biopsies were enrolled. Ishak
      fibrosis scoring revealed that 42.6% (69/162) of the patients achieved fibrosis
      regression (>=1-point decrease), 51.9% (84/162) remained stable, and 5.5% (9/162)
      showed progression (>=1-point increase). qFibrosis showed similar trends in the
      groups of regression and progression patients as evaluated by Ishak. However, in
      Ishak stable patients, qFibrosis revealed hitherto undetected changes, allowing
      for further subcategorization into regression ("Regression by qFibrosis"; 40/84,
      47.6%), stable (29/84, 34.5%), and progression ("Progression by qFibrosis";
      15/84, 17.9%) groups. These newly fine-tuned categories were supported by changes
      of morphological parameters of fibrosis, collagen percentage area, and liver
      stiffness measurements. In conclusion, qFibrosis can be used to quantitatively
      identify subtle changes of liver fibrosis in CHB patients after antiviral
      therapy.

PMID- 29445244
TI  - Permeability and ammonia selectivity in aquaporin TIP2;1: linking structure to
      function.
AB  - Aquaporin TIP2;1 is a protein channel permeable to both water and ammonia. The
      structural origin of ammonia selectivity remains obscure, but experiments have
      revealed that a double mutation renders it impermeable to ammonia without
      affecting water permeability. Here, we aim to reproduce and explain these
      observations by performing an extensive mutational study using microsecond long
      molecular dynamics simulations, applying the two popular force fields CHARMM36
      and Amber ff99SB-ILDN. We calculate permeabilities and free energies along the
      channel axis for ammonia and water. For one force field, the permeability of the
      double mutant decreases by a factor of 2.5 for water and 4 for ammonia,
      increasing water selectivity by a factor of 1.6. We attribute this effect to
      decreased entropy of water in the pore, due to the observed increase in pore
      water interactions and narrower pore. Additionally, we observe spontaneous
      opening and closing of the pore on the cytosolic side, which suggests a gating
      mechanism for the pore. Our results show that sampling methods and simulation
      times are sufficient to delineate even subtle effects of mutations on structure
      and function and to capture important long-timescale events, but also underline
      the importance of improving models further.

PMID- 29445245
TI  - Publisher Correction: Atomic scale imaging of magnetic circular dichroism by
      achromatic electron microscopy.
AB  - In Fig. 1 of the version of this Letter originally published, the word 'Subtract'
      was missing from the green box to the left of panel f. This has now been
      corrected in all versions of the Letter.

PMID- 29445246
TI  - The Economic Consequences of Hospital Admissions.
AB  - We use an event study approach to examine the economic consequences of hospital
      admissions for adults in two datasets: survey data from the Health and Retirement
      Study, and hospitalization data linked to credit reports. For non-elderly adults
      with health insurance, hospital admissions increase out-of-pocket medical
      spending, unpaid medical bills and bankruptcy, and reduce earnings, income,
      access to credit and consumer borrowing. The earnings decline is substantial
      compared to the out-of-pocket spending increase, and is minimally insured prior
      to age-eligibility for Social Security Retirement Income. Relative to the insured
      non-elderly, the uninsured non-elderly experience much larger increases in unpaid
      medical bills and bankruptcy rates following a hospital admission. Hospital
      admissions trigger less than 5 percent of all bankruptcies.

PMID- 29445247
TI  - De Novo Asymmetric Synthesis and Biological Analysis of the Daumone Pheromones in
      Caenorhabditis elegans and in the Soybean Cyst Nematode Heterodera glycines.
AB  - The de novo asymmetric total syntheses of daumone 1, daumone 3 along with 5 new
      analogs are described. The key steps of our approach are: the diastereoselective
      palladium catalyzed glycosylation reaction; the Noyori reduction of 2-acetylfuran
      and an ynone, which introduce the absolute stereochemistry of the sugar and
      aglycon portion of daumone; and an Achmatowicz rearrangement, an epoxidation and
      a ring opening installing the remaining asymmetry of daumone. The synthetic
      daumones 1 and 3 as well as related analogs were evaluated for dauer activity in
      C. elegans and for effects on hatching of the related nematode H. glycines. This
      data provides additional structure activity relationships (SAR) that further
      inform the study of nematode signaling.

PMID- 29445248
TI  - Friendship, curiosity and the city: Dementia friends and memory walks in
      Liverpool.
AB  - The city is not just a context for friendships or a problem to be solved through
      them; it can be a catalyst for these relationships, sparking and strengthening
      connections between individuals and groups. Shared experiences of and curiosity
      in cities - expressed through practices that include revisiting familiar places
      and exploring others for the first time - can draw people together in beneficial
      ways. These principles underpin a health and wellbeing agenda, pioneered in
      Liverpool, which encourages people to 'take notice' and 'connect' - two of five
      'ways to wellbeing' promoted through the Liverpool Decade of Health and
      Wellbeing. This paper focusses upon one particular set of schemes and
      relationships which brings all this into focus: befriending schemes designed to
      support people with dementia, which engage with objects and places as catalysts
      for connection. These observations shed a broader light upon the meanings and
      uses of friendship, with particular reference to cities.

PMID- 29445249
TI  - Overexpression of GRK3, Promoting Tumor Proliferation, Is Predictive of Poor
      Prognosis in Colon Cancer.
AB  - Deregulation of G protein-coupled receptor kinase 3 (GRK3), which belongs to a
      subfamily of kinases called GRKs, acts as a promoter mechanism in some cancer
      types. Our study found that GRK3 was significantly overexpressed in 162 pairs of
      colon cancer tissues than in the matched noncancerous mucosa (P < 0.01). Based on
      immunohistochemistry staining of TMAs, GRK3 was dramatically stained positive in
      primary colon cancer (130/180, 72.22%), whereas it was detected minimally or
      negative in paired normal mucosa specimens (50/180, 27.78%). Overexpression of
      GRK3 was closely correlated with AJCC stage (P = 0.001), depth of tumor invasion
      (P < 0.001), lymph node involvement (P = 0.004), distant metastasis (P = 0.016),
      and histologic differentiation (P = 0.004). Overexpression of GRK3 is an
      independent prognostic indicator that correlates with poor survival in colon
      cancer patients. Consistent with this, downregulation of GRK3 exhibited decreased
      cell growth index, reduction in colony formation ability, elevated cell apoptosis
      rate, and impaired colon tumorigenicity in a xenograft model. Hence, a specific
      overexpression of GRK3 was observed in colon cancer, GRK3 potentially
      contributing to progression by mediating cancer cell proliferation and functions
      as a poor prognostic indicator in colon cancer and potentially represent a novel
      therapeutic target for the disease.

PMID- 29445250
TI  - Magneto-elastic coupling across the first-order transition in the distorted
      kagome lattice antiferromagnet Dy3Ru4Al12.
AB  - Structural changes through the first-order paramagnetic-antiferromagnetic phase
      transition of Dy3Ru4Al12 at 7 K have been studied by means of X-ray diffraction
      and thermal expansion measurements. The compound crystallizes in a hexagonal
      crystal structure of Gd3Ru4Al12 type (P63/mmc space group), and no structural
      phase transition has been found in the temperature interval between 2.5 and 300
      K. Nevertheless, due to the spin-lattice coupling the crystal volume undergoes a
      small orthorhombic distortion of the order of 2*10-5 as the compound enters the
      antiferromagnetic state. We propose that the first-order phase transition is not
      driven by the structural changes but rather by the exchange interactions present
      in the system.

PMID- 29445251
TI  - [Sense of guilt in sexually abused children : Mediating role of avoidance coping
      on anxiety and self-esteem].
AB  - Prior studies have suggested self-blame and sense of guilt as important elements
      associated with the effects of childhood sexual abuse on adult survivors (Canton
      Cortes, Canton, Justicia & Cortes, 2011). However, few studies have explored the
      potential impact of the sense of guilt on outcomes in child victims. This study
      examines the mediating role of avoidance coping on the relationship between sense
      of guilt and outcomes (anxiety and self-esteem) in sexually abused children. The
      sample consisted of 447 sexually abused children (319 girls and 128 boys) aged 6
      to 12. Path analysis indicated that children with higher feelings of guilt about
      the abuse showed more anxiety and lower levels of self-esteem. Indirect effects
      also indicated that sense of guilt predicted avoidance coping, which in turn
      contributed to higher anxiety and lower self-esteem. This model, which fits the
      data well for both girls and boys, explains 24.4 % of the variance in anxiety and
      11.2 % of the variance in self-esteem. Results suggest that sense of guilt is an
      important target for clinical intervention with sexually abused children.

PMID- 29445252
TI  - Implications of Measurement Assay Type in Design of HIV Experiments.
AB  - Time series measurements of circular viral episome (2-LTR) concentrations enable
      indirect quantification of persistent low-level Human Immunodeficiency Virus
      (HIV) replication in patients on Integrase-Inhibitor intensified Combined
      Antiretroviral Therapy (cART). In order to determine the magnitude of these low
      level infection events, blood has to be drawn from a patients at a frequency and
      volume that is strictly regulated by the Institutional Review Board (IRB). Once
      the blood is drawn, the 2-LTR concentration is determined by quantifying the
      amount of HIV DNA present in the sample via a PCR (Polymerase Chain Reaction)
      assay. Real time quantitative Polymerase Chain Reaction (qPCR) is a widely used
      method of performing PCR; however, a newer droplet digital Polymerase Chain
      Reaction (ddPCR) method has been shown to provide more accurate quantification of
      DNA. Using a validated model of HIV viral replication, this paper demonstrates
      the importance of considering DNA quantification assay type when optimizing
      experiment design conditions. Experiments are optimized using a Genetic Algorithm
      (GA) to locate a family of suboptimal sample schedules which yield the highest
      fitness. Fitness is defined as the expected information gained in the experiment,
      measured by the Kullback-Leibler Divergence (KLD) between the prior and posterior
      distributions of the model parameters. We compare the information content of the
      optimized schedules to uniform schedules as well as two clinical schedules
      implemented by researchers at UCSF and the University of Melbourne. This work
      shows that there is a significantly greater gain information in experiments using
      a ddPCR assay vs. a qPCR assay and that certain experiment design considerations
      should be taken when using either assay.

PMID- 29445253
TI  - Mitochondrial (Dys) Function in Inflammaging: Do MitomiRs Influence the
      Energetic, Oxidative, and Inflammatory Status of Senescent Cells?
AB  - A relevant feature of aging is chronic low-grade inflammation, termed
      inflammaging, a key process promoting the development of all major age-related
      diseases. Senescent cells can acquire the senescence-associated (SA) secretory
      phenotype (SASP), characterized by the secretion of proinflammatory factors
      fuelling inflammaging. Cellular senescence is also accompanied by a deep
      reshaping of microRNA expression and by the modulation of mitochondria activity,
      both master regulators of the SASP. Here, we synthesize novel findings regarding
      the role of mitochondria in the SASP and in the inflammaging process and propose
      a network linking nuclear-encoded SA-miRNAs to mitochondrial gene regulation and
      function in aging cells. In this conceptual structure, SA-miRNAs can translocate
      to mitochondria (SA-mitomiRs) and may affect the energetic, oxidative, and
      inflammatory status of senescent cells. We discuss the potential role of several
      of SA-mitomiRs (i.e., let-7b, miR-1, miR-130a-3p, miR-133a, miR-146a-5p, miR-181c
      5p, and miR-378-5p), using miR-146a as a proof-of-principle model. Finally, we
      propose a comprehensive, metabolic, and epigenetic view of the senescence
      process, in order to amplify the range of possible approaches to target
      inflammaging, with the ultimate goal of decelerating the aging rate, postponing
      or blunting the development of age-related diseases.

PMID- 29445254
TI  - Cigarette Smoke Exposure Inhibits Bacterial Killing via TFEB-Mediated Autophagy
      Impairment and Resulting Phagocytosis Defect.
AB  - Introduction: Cigarette smoke (CS) exposure is the leading risk factor for COPD
      emphysema pathogenesis. A common characteristic of COPD is impaired phagocytosis
      that causes frequent exacerbations in patients leading to increased morbidity.
      However, the underlying mechanism is unclear. Hence, we investigated if CS
      exposure causes autophagy impairment as a mechanism for diminished bacterial
      clearance via phagocytosis by utilizing murine macrophages (RAW264.7 cells) and
      Pseudomonas aeruginosa (PA01-GFP) as an experimental model. Methods: Briefly, RAW
      cells were treated with cigarette smoke extract (CSE), chloroquine (autophagy
      inhibitor), TFEB-shRNA, CFTR(inh)-172, and/or fisetin prior to bacterial
      infection for functional analysis. Results: Bacterial clearance of PA01-GFP was
      significantly impaired while its survival was promoted by CSE (p < 0.01),
      autophagy inhibition (p < 0.05; p < 0.01), TFEB knockdown (p < 0.01; p < 0.001),
      and inhibition of CFTR function (p < 0.001; p < 0.01) in comparison to the
      control group(s) that was significantly recovered by autophagy-inducing
      antioxidant drug, fisetin, treatment (p < 0.05; p < 0.01; and p < 0.001).
      Moreover, investigations into other pharmacological properties of fisetin show
      that it has significant mucolytic and bactericidal activities (p < 0.01; p <
      0.001), which warrants further investigation. Conclusions: Our data suggests that
      CS-mediated autophagy impairment as a critical mechanism involved in the
      resulting phagocytic defect, as well as the therapeutic potential of autophagy
      inducing drugs in restoring is CS-impaired phagocytosis.

PMID- 29445255
TI  - Cigarette Smoking and Adipose Tissue: The Emerging Role in Progression of
      Atherosclerosis.
AB  - Smoking is an established risk factor for atherosclerosis through several
      underlying pathways. Moreover, in the development of atherosclerotic plaque
      formation, obesity, defined as excess fat mass accumulation, also plays a vital
      role in dyslipidemia and insulin resistance. Substantial evidence shows that
      cigarette smoking induces multiple pathological effects in adipose tissue, such
      as differentiation of adipocytes, lipolysis, and secretion properties in adipose
      tissue. Therefore, there is an emerging speculation in which adipose tissue
      abnormality induced by smoking or nicotine is likely to accelerate the
      progression of atherosclerosis. Herein, this review aims to investigate the
      possible interplay between smoking and adipose tissue dysfunction in the
      development of atherosclerosis.

PMID- 29445256
TI  - Distinct Signature of Oxylipid Mediators of Inflammation during Infection and
      Asymptomatic Colonization by E. coli in the Urinary Bladder.
AB  - Urinary tract infection (UTI) is an extremely common infectious disease.
      Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of
      UTI. Asymptomatic bacteriuric E. coli (ABEC) strains successfully colonize the
      urinary tract resulting in asymptomatic bacteriuria (ABU) and do not induce
      symptoms associated with UTI. Oxylipids are key signaling molecules involved in
      inflammation. Based on the distinct clinical outcomes of E. coli colonization, we
      hypothesized that UPEC triggers the production of predominantly proinflammatory
      oxylipids and ABEC leads to production of primarily anti-inflammatory or
      proresolving oxylipids in the urinary tract. We performed quantitative detection
      of 39 oxylipid mediators with proinflammatory, anti-inflammatory, and
      proresolving properties, during UTI and ABU caused by genetically distinct E.
      coli strains in the murine urinary bladder. Our results reveal that infection
      with UPEC causes an increased accumulation of proinflammatory oxylipids as early
      as 6 h postinoculation, compared to controls. To the contrary, ABEC colonization
      leads to decreased accumulation of proinflammatory oxylipids at the early time
      point compared to UPEC infection but does not affect the level of proresolving
      oxylipids. This report represents the first comprehensive investigation on the
      oxylipidome during benign ABEC colonization observed in ABU and acute
      inflammation triggered by UPEC leading to UTI.

PMID- 29445258
TI  - Inflammatory and Immune-Mediated Cutaneous Diseases.

PMID- 29445257
TI  - Comparison of Oropharyngeal Microbiota from Children with Asthma and Cystic
      Fibrosis.
AB  - A genuine microbiota resides in the lungs which emanates from the colonization by
      the oropharyngeal microbiota. Changes in the oropharyngeal microbiota might be
      the source of dysbiosis observed in the lower airways in patients suffering from
      asthma or cystic fibrosis (CF). To examine this hypothesis, we compared the
      throat microbiota from healthy children (n = 62) and that from children with
      asthma (n = 27) and CF (n = 57) aged 6 to 12 years using 16S rRNA amplicon
      sequencing. Our results show high levels of similarities between healthy controls
      and children with asthma and CF revealing the existence of a core microbiome
      represented by Prevotella, Streptococcus, Neisseria, Veillonella, and
      Haemophilus. However, in CF, the global diversity, the bacterial load, and
      abundances of 53 OTUs were significantly reduced, whereas abundances of 6 OTUs
      representing opportunistic pathogens such as Pseudomonas, Staphylococcus, and
      Streptococcus were increased compared to those in healthy controls controls and
      asthmatics. Our data reveal a core microbiome in the throat of healthy children
      that persists in asthma and CF indicating shared host regulation favoring growth
      of commensals. Furthermore, we provide evidence for dysbiosis with a decrease in
      diversity and biomass associated with the presence of known pathogens consistent
      with impaired host defense in children with CF.

PMID- 29445260
TI  - An approximation theorem and generic convergence for equilibrium problems.
AB  - In this paper, we prove an approximation theorem for equilibrium problems and
      provide theoretical support for many algorithms. Simon's bounded rationality is
      illustrated by an approximation theorem, that is, bounded rationality is
      approaching full rationality as its ultimate goal. Furthermore, by the methods of
      set-valued analysis, we obtain the generic uniqueness and generic convergence of
      the solutions of monotone equilibrium problems in the sense of Baire category. As
      applications, we investigate the optimization problem, variational inequality
      problem and saddle point problem as special cases.

PMID- 29445259
TI  - Significant Cytokine mRNA Expression Changes Immediately after Initiation of
      Cardiopulmonary Resuscitation.
AB  - Introduction: The purpose of this study was to evaluate immediate immunological
      changes following cardiopulmonary resuscitation (CPR). mRNA expression levels of
      selected immunomodulatory cytokines in out-of-hospital cardiac arrest (OHCA)
      survivors were detected and correlated to clinical parameter. Methods: OHCA
      survivors with sustained unconsciousness after return of spontaneous circulation
      (ROSC) were included. PAXgene whole blood samples were drawn immediately after
      initiation of CPR and subsequently after 6 h, 12 h, 24 h, 48 h, and 72 h. TNF
      alpha, IL-8, IL-10, and IL-1ra mRNA levels were quantified by RT-qPCR and
      compared to multiple organ failure, 30-day survival, and the induction of
      therapeutic hypothermia (TH). Results: 25 patients (63 +/- 15 years) were
      enrolled presenting a characteristic time-dependent cytokine profile in the early
      postresuscitation period. High initial TNF-alpha and IL-8 mRNA levels were
      followed by a significant decrease. IL-1ra mRNA levels significantly increased
      beginning after 6 h. Nonsurvivors showed significantly higher IL-8 mRNA levels
      immediately after CPR. TH induced significantly higher IL-1ra mRNA levels
      compared to normothermia. Conclusion: Significant mRNA cytokine expression
      changes are already detectable immediately after initiation of CPR. These
      expressional changes are significantly different depending on 30-day survival. TH
      seems to attenuate proinflammatory immune reaction by a significant increase of
      IL-1ra mRNA levels. This trial is registered with DRKS00012940.

PMID- 29445261
TI  - On asphericity of convex bodies in linear normed spaces.
AB  - In 1960, Dvoretzky proved that in any infinite dimensional Banach space X and for
      any [Formula: see text] there exists a subspace L of X of arbitrary large
      dimension epsilon-iometric to Euclidean space. A main tool in proving this deep
      result was some results concerning asphericity of convex bodies. In this work, we
      introduce a simple technique and rigorous formulas to facilitate calculating the
      asphericity for each set that has a nonempty boundary set with respect to the
      flat space generated by it. We also give a formula to determine the center and
      the radius of the smallest ball containing a nonempty nonsingleton set K in a
      linear normed space, and the center and the radius of the largest ball contained
      in it provided that K has a nonempty boundary set with respect to the flat space
      generated by it. As an application we give lower and upper estimations for the
      asphericity of infinite and finite cross products of these sets in certain
      spaces, respectively.

PMID- 29445262
TI  - Degenerate Cauchy numbers of the third kind.
AB  - Since Cauchy numbers were introduced, various types of Cauchy numbers have been
      presented. In this paper, we define degenerate Cauchy numbers of the third kind
      and give some identities for the degenerate Cauchy numbers of the third kind. In
      addition, we give some relations between four kinds of the degenerate Cauchy
      numbers, the Daehee numbers and the degenerate Bernoulli numbers.

PMID- 29445263
TI  - Noncompaction cardiomyopathy and heterotaxy syndrome.
AB  - Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by compact
      and trabecular layers of the left ventricular myocardium. This cardiomyopathy may
      occur with congenital heart disease (CHD). Single cases document co-occurrence of
      LVNC and heterotaxy, but no data exist regarding the prevalence of this
      association. This study sought to determine whether a non-random association of
      LVNC and heterotaxy exists by evaluating the prevalence of LVNC in patients with
      heterotaxy. In a retrospective review of the Indiana Network for Patient Care, we
      identified 172 patients with heterotaxy (69 male, 103 female). Echocardiography
      and cardiac magnetic resonance imaging results were independently reviewed by two
      cardiologists to ensure reproducibility of LVNC. A total of 13/172 (7.5%)
      patients met imaging criteria for LVNC. The CHD identified in this subgroup
      included atrioventricular septal defects [11], dextrocardia [10], systemic and
      pulmonary venous return abnormalities [7], and transposition of the great
      arteries [5]. From this subgroup, 61% (n = 8) of the patients developed
      arrhythmias; and 61% (n = 8) required medical management for chronic heart
      failure. This study indicates that LVNC has increased prevalence among patients
      with heterotaxy when compared to the general population (0.014-1.3%) suggesting
      possible common genetic mechanisms. Interestingly, mice with a loss of function
      of Scrib or Vangl2 genes showed abnormal compaction of the ventricles, anomalies
      in cardiac looping, and septation defects in previous studies. Recognition of the
      association between LVNC and heterotaxy is important for various reasons. First,
      the increased risk of arrhythmias demonstrated in our population. Secondly,
      theoretical risk of thromboembolic events remains in any LVNC population.
      Finally, many patients with heterotaxy undergo cardiac surgery (corrective and
      palliative) and when this is associated with LVNC, patients should be presumed to
      incur a higher peri-operative morbidity based on previous studies. Further
      research will continue to determine long-term and to corroborate genetic
      pathways.

PMID- 29445264
TI  - Exercise program improved subjective dry eye symptoms for office workers.
AB  - Introduction: We investigated the benefits of a cognitive behavior therapy-based
      exercise program to reduce the dry eye symptoms of office workers. Materials and
      methods: We recruited 11 office workers with dry eye symptoms, aged 31-64 years,
      who voluntarily participated in group health guidance at a manufacturing company.
      Participants learned about the role of physical activity and exercise in
      enhancing wellness and performed an exercise program at home 3 days per week for
      10 weeks. We estimated the indexes of body composition, dry eye symptoms, and
      psychological distress using the Dry Eye-Related Quality of Life Score and the
      World Health Organization's Subjective Well-Being Inventory questionnaires pre-
      and postintervention. Results: The 10-week exercise program and the
      questionnaires were completed by 48.1% (39 of 81) of the participants. Body
      composition did not change pre- and postintervention. However, the average of the
      Dry Eye-Related Quality of Life Score scores in participants with subjective dry
      eye significantly improved after the intervention. Moreover, the World Health
      Organization's Subjective Well-Being Inventory positive well-being score tended
      to increase after the intervention. Conclusion: In this study, we showed that a
      10-week exercise program improved subjective dry eye symptoms of healthy office
      workers. Our study suggests that a cognitive behavior therapy-based exercise
      program can play an important role in the treatment of patients with dry eye
      disease.

PMID- 29445266
TI  - Are frail elderly patients treated in a CGA unit more satisfied with their
      hospital care than those treated in conventional acute medical care?
AB  - Objectives: Our aim was to study whether the acute care of frail elderly patients
      directly admitted to a comprehensive geriatric assessment (CGA) unit is superior
      to the care in a conventional acute medical care unit in terms of patient
      satisfaction. Design: TREEE (Is the TReatment of frail Elderly patients Effective
      in an Elderly care unit?) is a clinical, prospective, controlled, one-center
      intervention trial comparing acute treatment in CGA units and in conventional
      wards. Setting: This study was conducted in the NAL-Uddevalla county hospital in
      western Sweden. Participants: In this follow-up to the TREEE study, 229 frail
      patients, aged >=75 years, in need of acute in-hospital treatment, were eligible.
      Of these patients, 139 patients were included in the analysis, 72 allocated to
      the CGA unit group and 67 to the conventional care group. Mean age was 85 years
      and 65% were female. Intervention: Direct admittance to an acute elderly care
      unit with structured, systematic interdisciplinary CGA-based care, compared to
      conventional acute medical care via the emergency room. Measurements: The primary
      outcome was the satisfaction reported by the patients shortly after discharge
      from hospital. A four-item confidential questionnaire was used. Responses were
      given on a 4-graded scale. Results: The response rate was 61%. In unadjusted
      analyses, significantly more patients in the intervention group responded
      positively to the following three questions about the hospitalization: "Did you
      get the nursing from the ward staff that you needed?" (p=0.003), "Are you
      satisfied with the information you received on your diseases and medication?"
      (p=0.016), and "Are you satisfied with the planning before discharge from the
      hospital?" (p=0.032). After adjusted analyses by multiple regression, a
      significant difference in favor of the intervention remained for the first
      question (p=0.027). Conclusion: Acute care in a CGA unit with direct admission
      was associated with higher levels of patient satisfaction compared with
      conventional acute care via the emergency room.

PMID- 29445265
TI  - New frontiers in oncolytic viruses: optimizing and selecting for virus strains
      with improved efficacy.
AB  - Oncolytic viruses have demonstrated selective replication and killing of tumor
      cells. Different types of oncolytic viruses - adenoviruses, alphaviruses, herpes
      simplex viruses, Newcastle disease viruses, rhabdoviruses, Coxsackie viruses, and
      vaccinia viruses - have been applied as either naturally occurring or engineered
      vectors. Numerous studies in animal-tumor models have demonstrated substantial
      tumor regression and prolonged survival rates. Moreover, clinical trials have
      confirmed good safety profiles and therapeutic efficacy for oncolytic viruses.
      Most encouragingly, the first cancer gene-therapy drug - Gendicine, based on
      oncolytic adenovirus type 5 - was approved in China. Likewise, a second
      generation oncolytic herpes simplex virus-based drug for the treatment of
      melanoma has been registered in the US and Europe as talimogene laherparepvec.

PMID- 29445267
TI  - A patient and community-centered approach selecting endpoints for a randomized
      trial of a novel advance care planning tool.
AB  - Background: Despite a movement toward patient-centered outcomes, best practices
      on how to gather and refine patients' perspectives on research endpoints are
      limited. Advanced care planning (ACP) is inherently patient centered and would
      benefit from patient prioritization of endpoints for ACP-related tools and
      studies. Objective: This investigation sought to prioritize patient-centered
      endpoints for the content and evaluation of an ACP video being developed for
      patients undergoing major surgery. We also sought to highlight an approach using
      complementary engagement and research strategies to document priorities and
      preferences of patients and other stakeholders. Materials and methods: Endpoints
      identified from a previously published environmental scan were operationalized
      following rating by a caregiver co-investigator, refinement by a patient co
      investigator, review by a stakeholder committee, and validation by patients and
      family members. Finalized endpoints were taken to a state fair where members of
      the public who indicated that they or a loved one had undergone major surgery
      prioritized their most relevant endpoints and provided comments. Results: Of the
      initial 50 ACP endpoints identified from the review, 12 endpoints were selected
      for public prioritization. At the state fair, 359 individuals prioritized the
      endpoints, the highest ranking of which was having a meaningful conversation with
      a physician before surgery (57%). Conclusion: Using a novel combination of
      engagement and research techniques provided the opportunity to understand which
      endpoints were most important to patients and families and fostered framework
      development clarifying the differential contributions of engagement and research.
      Results from this study ultimately changed the content and evaluation of the ACP
      video.

PMID- 29445268
TI  - Genome-editing applications of CRISPR-Cas9 to promote in vitro studies of
      Alzheimer's disease.
AB  - Genetic variations play an important role in the clinical presentation and
      progression of Alzheimer's disease (AD), especially early-onset Alzheimer's
      disease. Hundreds of mutations have been reported with the majority resulting
      from alterations in beta-amyloid precursor protein (APP), presenilin 1 (PSEN1),
      or presenilin 2 (PSEN2) genes. The roles of these mutations in the pathogenesis
      of AD have been classically confirmed or refuted through functional studies,
      where the mutations are cloned, inserted into cell lines, and monitored for
      changes in various properties including cell survival, amyloid production, or
      Abeta42/40 ratio. However, these verification studies tend to be expensive, time
      consuming, and inconsistent. Recently, the clustered regularly interspaced short
      palindromic repeats-CRISPR-associated protein 9 (CRISPR-Cas9) system was
      developed, which improves sequence-specific gene editing in cell lines, organs,
      and animals. CRISPR-Cas9 is a promising tool for the generation of models of
      human genetic diseases and could facilitate the establishment of new animal AD
      models and the observation of dynamic bioprocesses in AD. Here, we recapitulated
      the history of CRISPR technology, recent progress, and, especially, its potential
      applications in AD-related genetic, animal modeling, and functional studies.

PMID- 29445269
TI  - An open-label, prospective interventional study of the tolerability and efficacy
      of 0.4 mg oral tamsulosin oral controlled absorption system in men with lower
      urinary tract symptoms associated with benign prostatic hyperplasia who are
      unsatisfied with treatment with 0.2 mg tamsulosin.
AB  - Purpose: The aim of this study was to investigate the efficacy and tolerability
      of switching from 0.2 mg tamsulosin to 0.4 mg tamsulosin oral controlled
      absorption system (OCAS) over a 12-week period in Taiwanese men with lower
      urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).
      Patients and methods: Taiwanese male patients who were dissatisfied with
      treatment with 0.2 mg tamsulosin were enrolled in this clinical study and
      switched to 0.4 mg tamsulosin OCAS. Efficacy was assessed over a 12-week period
      by an International Prostate Symptom Score (IPSS) questionnaire and analysis of
      urinary flow by uroflowmetry. Results: A statistically significant improvement
      was observed in total IPSS scores from baseline (14.94+/-7.41, moderate) to 12
      weeks (7.36+/-5.77, mild) in 81 patients who were switched from 0.2 to 0.4 mg
      tamsulosin OCAS (P<0.001). The IPSS subscores for storage, voiding, nocturia, and
      quality of life (QOL) were also significantly improved over the 12-week period.
      Uroflowmetry analysis demonstrated significantly increased maximum flow rate,
      average flow rate, and mean voided volume from baseline to the end of the 12-week
      period. The 0.4 mg tamsulosin OCAS dose was well tolerated, with only mild
      dizziness (five patients) and headache (two patients) as the most frequent
      adverse events. No clinically significant reduction was observed in blood
      pressure or vital signs. Conclusion: Treatment with 0.4 mg tamsulosin OCAS in
      Taiwanese men with LUTS associated with BPH who were dissatisfied with 0.2 mg
      tamsulosin significantly improved IPSS scores, urinary flow, and QOL and was well
      tolerated, suggesting that this should be the recommended dose offered to
      Taiwanese male patients.

PMID- 29445270
TI  - Alterations of the default mode network and cognitive impairments in patients
      with chronic obstructive pulmonary disease.
AB  - Background and objectives: Cognitive impairment is a common extrapulmonary
      comorbidity in COPD patients. The default mode network (DMN) plays a critical
      role in maintaining the normal activities of humans, and its function can be
      evaluated by resting state functional magnetic resonance imaging. The aim of this
      study was to investigate the correlations between cognition and function changes
      of the DMN in COPD patients. Methods: One hundred and thirteen eligible
      participants including 30 control subjects and 83 COPD patients matched for
      demographic characteristics were recruited. All participants performed cognitive
      function tests and underwent resting state functional magnetic resonance imaging.
      Results: The total cognitive function scores of COPD patients were significantly
      different from those of control subjects (P<0.05) and worsened with the degree of
      airflow obstruction. The activated brain regions in the DMN of COPD patients were
      less than those of normal controls. Six activated brain regions in the DMN were
      found to develop significantly different functional connectivity (FC) values
      among the subjects. Meanwhile, the FC values of the left posterior cingulate
      cortex and left hippocampus correlated well with cognitive functions and
      pulmonary function. Conclusion: COPD patients have cognitive impairments that
      correlate well with disease severity. FC changes in activated brain regions in
      the DMN may predict cognitive impairment, and the left posterior cingulate cortex
      and left hippocampus may be important brain regions related to cognitive
      impairment in COPD patients.

PMID- 29445271
TI  - Immune cell response to strenuous resistive breathing: comparison with whole body
      exercise and the effects of antioxidants.
AB  - Background/hypothesis: Whole body exercise (WBE) changes lymphocyte subset
      percentages in peripheral blood. Resistive breathing, a hallmark of diseases of
      airway obstruction, is a form of exercise for the inspiratory muscles. Strenuous
      muscle contractions induce oxidative stress that may mediate immune alterations
      following exercise. We hypothesized that inspiratory resistive breathing (IRB)
      alters peripheral blood lymphocyte subsets and that oxidative stress mediates
      lymphocyte subpopulation alterations following both WBE and IRB. Patients and
      methods: Six healthy nonathletes performed two WBE and two IRB sessions for 45
      minutes at 70% of VO2 maximum and 70% of maximum inspiratory pressure (Pimax),
      respectively, before and after the administration of antioxidants (vitamins E, A,
      and C for 75 days, allopurinol for 30 days, and N-acetylcysteine for 3 days).
      Blood was drawn at baseline, at the end of each session, and 2 hours into
      recovery. Lymphocyte subsets were determined by flow cytometry. Results: Before
      antioxidant supplementation at both WBE end and IRB end, the natural killer cell
      percentage increased, the T helper cell (CD3+ CD4+) percentage was reduced, and
      the CD4/CD8 ratio was depressed, a response which was abolished by antioxidants
      only after IRB. Furthermore, at IRB end, antioxidants promoted CD8+ CD38+ and
      blunted cytotoxic T-cell percentage increase. CD8+ CD45RA+ cell percentage
      changes were blunted after antioxidant supplementation in both WBE and IRB.
      Conclusion: We conclude that IRB produces (as WBE) changes in peripheral blood
      lymphocyte subsets and that oxidative stress is a major stimulus predominantly
      for IRB-induced lymphocyte subset alterations.

PMID- 29445272
TI  - CT densitometry in emphysema: a systematic review of its clinical utility.
AB  - Background: The aim of the study was to assess the relationship between computed
      tomography (CT) densitometry and routine clinical markers in patients with
      chronic obstructive pulmonary disease (COPD) and alpha-1 anti-trypsin deficiency
      (AATD). Methods: Multiple databases were searched using a combination of
      pertinent terms and those articles relating quantitatively measured CT
      densitometry to clinical outcomes. Studies that used visual scoring only were
      excluded, as were those measured in expiration only. A thorough review of
      abstracts and full manuscripts was conducted by 2 reviewers; data extraction and
      assessment of bias was conducted by 1 reviewer and the 4 reviewers independently
      assessed for quality. Pooled correlation coefficients were calculated, and
      heterogeneity was explored. Results: A total of 112 studies were identified, 82
      being suitable for meta-analysis. The most commonly used density threshold was 
      950 HU, and a significant association between CT density and all included
      clinical parameters was demonstrated. There was marked heterogeneity between
      studies secondary to large variety of disease severity within commonly included
      cohorts and differences in CT acquisition parameters. Conclusion: CT density
      shows a good relationship to clinically relevant parameters; however, study
      heterogeneity and lack of longitudinal data mean that it is difficult to compare
      studies or derive a minimal clinically important difference. We recommend that
      international consensus is reached to standardize CT conduct and analysis in
      future COPD and AATD studies.

PMID- 29445273
TI  - New bacterial growth in bronchial secretions after bronchoscopic valve
      implantation.
AB  - Background: Bronchoscopic valve implantation is an established treatment in
      selected patients with severe lung emphysema. There is evidence in literature of
      increased bacterial colonization of various implants. So far, it is unclear if an
      increased bacterial colonization can also be observed after endoscopic valve
      therapy. Methods: Retrospective analysis of patients with examination of the
      bronchial secretions for presence or change of bacterial growth before and after
      valve implantation. Results: Overall, 144 patients who underwent bronchoscopic
      follow-up after valve implantation were included in this analysis. Prior to valve
      placement, only 7 out of 144 consecutive emphysema patients (5%) presented with
      evidence of bacterial colonization, whereas 137 patients (95%) showed no
      bacterial growth prior to valve placement. One hundred seven out of the 137
      patients (78%) showed new bacterial growth after valve implantation. Almost 38%
      of the patients who presented with a new bacterial growth had evidence of
      Viridans streptococci, Rothia mucilaginousa and Neisseria species simultaneously,
      as bacterial colonization. Pathogenic bacterial growth was recorded for
      Staphylococcus aureus (18%), Pseudomonas aeruginosa (13%) and Stenotrophomonas
      maltophilia (9%) microorganisms. There was also a significant bacterial growth by
      Moraxella catarrhalis (26%) and anaerobic bacteria (23%), especially in patients
      with complete atelectasis after successful endoscopic lung volume reduction. For
      all of the 7 patients, the presented initial bacterial colonization showed a
      change in the flora after bronchoscopy valve implantation. Conclusion: In this
      study we observed an increased bacterial colonization in the long term after
      valve implantation. This finding needs further evaluation regarding its possible
      clinical relevance but should be taken into consideration in the follow-up of
      these patients.

PMID- 29445274
TI  - Endoplasmic reticulum chaperone GRP78 mediates cigarette smoke-induced
      necroptosis and injury in bronchial epithelium.
AB  - Introduction: Bronchial epithelial cell death and airway inflammation induced by
      cigarette smoke (CS) have been involved in the pathogenesis of COPD. GRP78,
      belonging to heat shock protein 70 family, has been implicated in cell death and
      inflammation, while little is known about its roles in COPD. Here, we demonstrate
      that GRP78 regulates CS-induced necroptosis and injury in bronchial epithelial
      cells. Materials and methods: GRP78 and necroptosis markers were examined in
      human bronchial epithelial (HBE) cell line, primary mouse tracheal epithelial
      cells, and mouse lungs. siRNA targeting GRP78 gene and necroptosis inhibitor were
      used. Expression of inflammatory cytokines, mucin MUC5AC, and related signaling
      pathways were detected. Results: Exposure to CS significantly increased the
      expression of GRP78 and necroptosis markers in HBE cell line, primary mouse
      tracheal epithelial cells, and mouse lungs. Inhibition of GRP78 significantly
      suppressed CS extract (CSE)-induced necroptosis. Furthermore, GRP78-necroptosis
      cooperatively regulated CSE-induced inflammatory cytokines such as interleukin 6
      (IL6), IL8, and mucin MUC5AC in HBE cells, likely through the activation of
      nuclear factor (NF-kappaB) and activator protein 1 (AP-1) pathways, respectively.
      Conclusion: Taken together, our results demonstrate that GRP78 promotes CSE
      induced inflammatory response and mucus hyperproduction in airway epithelial
      cells, likely through upregulation of necroptosis and subsequent activation of NF
      kappaB and AP-1 pathways. Thus, inhibition of GRP78 and/or inhibition of
      necroptosis could be the effective therapeutic approaches for the treatment of
      COPD.

PMID- 29445275
TI  - Burden of COPD in Nepal.
AB  - Background: COPD is a globally significant public health problem and is the
      second leading cause of mortality. This study presents the health burden of COPD
      in Nepal using the Global Burden of Disease (GBD) study 2016 dataset. Methods:
      This study used the data from the GBD repository presenting morbidity and
      mortality attributed to COPD, by sex and age. In GBD 2016, due to a lack of the
      primary source of data in Nepal, estimations on morbidity and mortality of COPD
      were based on its predictive covariates. Years of life lost (YLLs) were
      calculated based on the cause of death estimations, applying GBD's Cause of Death
      Ensemble modeling. Likewise, years lived with disability (YLDs) were calculated
      by multiplying the prevalence of each sequela by the disability weight.
      Disability-adjusted life years (DALYs) were derived as the sum of YLLs and YLDs.
      Results: Between 1990 and 2016, the estimated age-standardized mortality rate due
      to COPD was decreasing for both genders, but the decline was much higher among
      males. Unlike the high rate of incidence among males, the age-standardized DALYs
      were found to be high among females (2,274.9 [95% UI: 1,702.0-2,881.5] per
      100,000). YLLs contributed around 80% of DALYs due to COPD in 2016. Age
      standardized YLLs rate was higher among females, with a value of 1,860 (95%
      uncertainty interval (UI): 1,282.8-2,472.8) vs 1,547.6 (95% UI: 992.1-2,018.5)
      among the males per 100,000 population. Conclusion: The prevalence and incidence
      of COPD remained almost stationary over the years, but still very high. Though
      the incidence and prevalence of disease were high among males, the death rate and
      DALYs were more significant among females throughout the years. If the current
      situation prevails, the burden of COPD will continue to increase in the country.
      Hence, comprehensive social, environmental, and behavioral approaches to curtail
      the risk factors along with early identification, treatment, and management of
      COPD is of utmost importance.

PMID- 29445278
TI  - Increased viability of fibroblasts when pretreated with ceria nanoparticles
      during serum deprivation.
AB  - Conditions of cellular stress are often the cause of cell death or dysfunction.
      Sustained cell stress can lead to several health complications, such as extensive
      inflammatory responses, tumor growth, and necrosis. To prevent disease and
      protect human tissue during these conditions and to avoid medication side
      effects, nanomaterials with unique characteristics have been applied to
      biological systems. This paper introduces the pretreatment in human dermal
      fibroblasts with cerium oxide nanoparticles during nutritional stress. For this
      purpose, human dermal fibroblast cells received cell culture media with
      concentrations of 250 ug/mL and 500 ug/mL of nano-cerium oxide before being
      exposed to 24, 48, and 72 hours of serum starvation. Contrast images demonstrated
      higher cell confluence and cell integrity in cells pretreated with ceria
      nanoparticles compared to untreated cells. It was confirmed by MTS assay after 72
      hours of serum starvation that higher cell viability was achieved with ceria
      nanoparticles. The results demonstrate the potential of cerium oxide
      nanoparticles as protective agents during cellular starvation.

PMID- 29445276
TI  - Redox-responsive F127-folate/F127-disulfide bond-d-alpha-tocopheryl polyethylene
      glycol 1000 succinate/P123 mixed micelles loaded with paclitaxel for the reversal
      of multidrug resistance in tumors.
AB  - Introduction: The development of nanodrug carriers utilizing tumor
      microenvironment has become a hotspot in reversing multidrug resistance (MDR).
      Materials and methods: This study synthesized a redox-sensitive copolymer,
      Pluronic F127-disulfide bond-d-alpha-tocopheryl polyethylene glycol 1000
      succinate (FSST), through the connection of the reduction-sensitive disulfide
      bond between F127 and d-alpha-tocopheryl polyethylene glycol 1000 succinate. This
      polymer could induce the elevation of reactive oxygen species (ROS) levels,
      ultimately resulting in cytotoxicity. Moreover, the redox-responsive mixed
      micelles, F127-folate (FA)/FSST/P123 (FFSSTP), based on FSST, Pluronic F127-FA,
      and Pluronic P123, were prepared to load paclitaxel (PTX). Results: The in vitro
      release study demonstrated that FFSSTP/PTX accelerated the PTX release through
      the breakage of disulfide bond in reductive environment. In cellular experiment,
      FFSSTP/PTX induced significant apoptosis in PTX-resistant MCF-7/PTX cells through
      inhibiting adenosine triphosphate (ATP)-binding cassette proteins from pumping
      out PTX by interfering with the mitochondrial function and ATP synthesis.
      Furthermore, FFSSTP/PTX induced apoptosis through elevating the intracellular
      levels of ROS. Conclusion: FFSSTP could become a potential carrier for the
      treatment of MDR tumors.

PMID- 29445277
TI  - Effects of silica-gentamicin nanohybrids on osteogenic differentiation of human
      osteoblast-like SaOS-2 cells.
AB  - Introduction: In recent years, there has been an increasing interest in silica
      (SiO2) nanoparticles (NPs) as drug delivery systems. This interest is mainly
      attributed to the ease of their surface functionalization for drug loading. In
      orthopedic applications, gentamicin-loaded SiO2 NPs (nanohybrids) are frequently
      utilized for their prolonged antibacterial effects. Therefore, the possible
      adverse effects of SiO2-gentamicin nanohybrids on osteogenesis of bone-related
      cells should be thoroughly investigated to ensure safe applications. Materials
      and methods: The effects of SiO2-gentamicin nanohybrids on the cell viability and
      osteogenic differentiation of human osteoblast-like SaOS-2 cells were
      investigated, together with native SiO2 NPs and free gentamicin. Results: The
      results of Cell Count Kit-8 (CCK-8) assay show that both SiO2-gentamicin
      nanohybrids and native SiO2 NPs reduce cell viability of SaOS-2 cells in a dose
      dependent manner. Regarding osteogenesis, SiO2-gentamicin nanohybrids and native
      SiO2 NPs at the concentration range of 31.25-125 MUg/mL do not influence the
      osteogenic differentiation capacity of SaOS-2 cells. At a high concentration (250
      MUg/mL), both materials induce a lower expression of alkaline phosphatase (ALP)
      but an enhanced mineralization. Free gentamicin at concentrations of 6.26 and
      9.65 MUg/mL does not significantly influence the cell viability and osteogenic
      differentiation capacity of SaOS-2 cells. Conclusions: The results of this study
      suggest that both SiO2-gentamicin nanohybrids and SiO2 NPs show cytotoxic effects
      to SaOS-2 cells. Further investigation on the effects of SiO2-gentamicin
      nanohybrids on the behaviors of stem cells or other regular osteoblasts should be
      conducted to make a full evaluation of the safety of SiO2-gentamicin nanohybrids
      in orthopedic applications.

PMID- 29445279
TI  - EGFR-targeted photodynamic therapy by curcumin-encapsulated chitosan/TPP
      nanoparticles.
AB  - Background: Photodynamic therapy (PDT) is an effective therapy for cancers and is
      a minimally invasive therapy with low dark toxicity and limited side effects. PDT
      employs the combination of photosensitizers with a specific light source to
      produce reactive oxygen species (ROS) to damage tumor cells. Methods: We
      fabricated nanoparticles encapsulating curcumin through crosslinking chitosan and
      tripolyphosphate (TPP). Additionally, the chitosan was conjugated to epidermal
      growth factor in order to target the epidermal growth factor receptor (EGFR),
      overexpressed on cancer cells. To investigate PDT using fabricated nanoparticles,
      we measured cell viabilities and ROS production in relation to EGFR
      overexpressing gastric cancer cells and non-cancer gastric cells. Results: The
      targeting nanoparticles displayed a superior PDT effect in the cancer cell, with
      a resultant approximately fourfold decrease in the IC50. The PDT mechanism of
      curcumin-encapsulated nanoparticles is further identified as the generation of
      1O2, the major pathway in PDT. Conclusion: These curcumin-encapsulated
      chitosan/TPP nanoparticles are a promising targeted-PDT against EGFR
      overexpressing cancers.

PMID- 29445280
TI  - The differences between patients with panic disorder and healthy controls in
      psychophysiological stress profile.
AB  - Background: Alarming somatic symptoms, in particular, cardiovascular symptoms,
      are the characteristic feature of panic attacks. Increased cardiac mortality and
      morbidity have been found in these patients. Power spectral analysis of
      electrocardiogram R-R intervals is known to be a particularly successful tool in
      the detection of autonomic instabilities in various clinical disorders. Our study
      aimed to compare patients with panic disorder and healthy controls in heart rate
      variation (HRV) parameters (very-low-frequency [VLF], low-frequency [LF], and
      high-frequency [HF] band components of R-R interval) in baseline and during the
      response to the mental task. Subjects and methods: We assessed
      psychophysiological variables in 33 patients with panic disorder (10 men, 23
      women; mean age 35.9+/-10.7 years) and 33 age- and gender-matched healthy
      controls (10 men, 23 women; mean age 35.8+/-12.1 years). Patients were treatment
      naive. Heart rate, blood pressure, muscle tension, and HRV in basal conditions
      and after the psychological task were assessed. Power spectrum was computed for
      VLF (0.003-0.04 Hz), LF (0.04-0.15 Hz), and HF (0.15-0.40 Hz) bands using fast
      Fourier transformation. Results: In the baseline period, the VLF band was
      significantly lower in panic disorder group compared to controls (p<0.005). In
      the period of mental task, the LF/HF ratio was significantly higher in panic
      disorder patients compared to controls (p<0.05). No significant differences were
      found in the remaining parameters. There was a significant difference in DeltaHF
      and DeltaLF/HF ratio between patients and controls, with Delta increasing in
      patients and decreasing in controls. Conclusion: These findings revealed that
      patients suffering from panic disorder were characterized by relative sympathetic
      dominance (reactivity) in response to mental stress compared with healthy
      controls.

PMID- 29445281
TI  - Suicidal drug overdose following stroke in elderly patients: a retrospective
      population-based cohort study.
AB  - Purpose: The purpose of this study was to investigate the incidence and risk of
      suicidal drug overdose (SDO) after stroke in older patients. Methods: We enrolled
      patients aged 60-99 years who were diagnosed with new-onset stroke between 2002
      and 2013 and age-, sex-, and index-year-matched controls who did not have stroke.
      Patients with a history of SDO before enrollment were excluded. Both groups were
      observed until December 31, 2013. The primary end point was the occurrence of
      newly diagnosed SDO. The cumulative incidence rates of the study and control
      groups were estimated using the Kaplan-Meier method. Furthermore, we used the Cox
      proportional hazards model to identify risk factors for SDO. Results: We selected
      22,770 individuals. Among them, 11,385 were older patients (aged 60-99 years) who
      had newly diagnosed stroke and 11,385 were controls. Of the 22,770 individuals,
      275 (1.21%) had SDO during a mean follow-up period of 5.33+/-3.30 years,
      comprising 191 (1.68%) from the stroke group and 84 (0.74%) from the control
      group. Older patients with stroke had a significantly higher risk of SDO than the
      controls (adjusted hazard ratio: 2.288, 95% confidence interval [CI]: 1.746
      2.999, p<0.001). Moreover, in older patients with stroke, the risk significantly
      increased with the number of stroke events. Patients with depressive disorder or
      coronary disease had an increased risk of SDO. Additionally, benzodiazepines and
      anticoagulants were the two most commonly prescribed medications for SDO.
      Conclusion: Clinicians should be aware of the risk of SDO and risk factors in
      older patients with stroke. Psychological assessment and medication monitoring
      should be incorporated into current clinical diagnoses in neurology and
      treatments following stroke.

PMID- 29445282
TI  - Orexin/hypocretin levels in the cerebrospinal fluid and characteristics of
      patients with myotonic dystrophy type 1 with excessive daytime sleepiness.
AB  - Purpose: Myotonic dystrophy type 1 (DM1) is often characterized by excessive
      daytime sleepiness (EDS) and sleep-onset rapid eye movement periods caused by
      muscleblind-like protein 2. The EDS tends to persist even after treatment of
      sleep apnea. We measured the cerebrospinal fluid (CSF) orexin levels in DM1
      patients with EDS and compared the clinical characteristics with narcolepsy type
      1 and idiopathic hypersomnia (IHS) patients. Patients and methods: We measured
      the CSF orexin levels in 17 DM1 patients with EDS and evaluated subjective
      sleepiness using the Epworth Sleepiness Scale (ESS), objective sleepiness using
      mean sleep latency (MSL), and sleep apnea using apnea-hypopnea index (AHI). We
      compared the ESS scores and MSL between decreased (<=200 pg/mL) and normal (>200
      pg/mL) CSF orexin group in DM1 patients. Furthermore, we compared the CSF orexin
      levels, ESS scores, MSL, and AHI among patients with DM1, narcolepsy type 1
      (n=46), and IHS (n=30). Results: Seven DM1 patients showed decreased CSF orexin
      levels. There were significant differences in the ESS scores and MSL between
      decreased and normal CSF orexin groups in DM1 patients. The ESS scores showed no
      significant difference among patients with DM1, narcolepsy type 1, and IHS. The
      MSL in DM1 and IHS patients were significantly higher than narcolepsy type 1
      patients (p=0.01, p<0.001). The AHI in DM1 patients was significantly higher than
      narcolepsy type 1 patients (p=0.042) and was insignificantly different from IHS
      patients. The CSF orexin levels in DM1 patients were significantly lower than IHS
      patients and higher than narcolepsy type 1 patients (p<0.001, p<0.001).
      Conclusion: The CSF orexin levels of DM1 patients moderately decreased compared
      to those of IHS patients as the control group. However, the EDS of DM1 patients
      may not be explained by only orexin deficiency.

PMID- 29445283
TI  - Application value of selected serum indicators in the differential diagnosis of
      geriatric depression and transient depressive state.
AB  - Background: Transient depressive state (TDS) is a transient, negative emotional
      state caused by certain events or situations. Because of the similarity in
      depressive symptoms between depression and TDS that arise within 2 weeks of their
      onset, it is difficult to distinguish TDS from depression. The aims of the
      present study were to investigate the application value of selected serum
      indicators in the differential diagnosis of geriatric depression and TDS in the
      early stage and to provide evidence for treatment. Patients and methods: In this
      study, a total of 274 elderly patients were divided into the depression group
      (n=144) and the TDS group (n=130). All participants' serum samples were
      collected, and 9 selected serum indicators were analyzed. Afterward, 90 patients
      with depression and 90 patients with TDS were used to build the diagnostic model.
      A binary logistic regression analysis was used to establish regression models,
      and the area under the receiver operating characteristic (ROC) curve was drawn.
      Finally, another 54 patients with depression and 40 patients with TDS were used
      to validate our model. Results: For the 9 screening serum indicators, the 3 serum
      indicators selected to build the regression model were BDNF (P=0.001), IL-1beta
      (P<0.001), and cortisol (P<0.001). The regression equation was Y = 1/[1 + e-(
      16.258 - 0.018 (BDNF) + 0.256 (IL-1beta) + 0.093 (Cortisol))], and the ROC curve
      of combined detection was 0.926. The diagnostic rate of the logistic model was
      89.36%. Conclusion: The logistic regression model and ROC curves based on serum
      levels of BDNF, IL-1beta, and cortisol could distinguish depression from TDS in
      early stage, which could provide assistance to the differential diagnosis of
      geriatric depression and TDS.

PMID- 29445284
TI  - Efficacy, acceptability, and safety of adjunctive aripiprazole in treatment
      resistant depression: a meta-analysis of randomized controlled trials.
AB  - Background: Treatment-resistant depression (TRD) is common and potentially life
      threatening in adults, and the benefits and risks of adjunctive aripiprazole in
      these patients remain controversial. Therefore, we conducted a meta-analysis of
      randomized controlled trials (RCTs) to assess the efficacy, acceptability,
      safety, and quality of life of adjunctive aripiprazole in patients with TRD.
      Methods: RCTs published in PubMed, Web of Science, and Embase were systematically
      reviewed to evaluate the efficacy and safety profiles of TRD patients who were
      treated with adjunctive aripiprazole. The main outcome measures included response
      rate, remission rate, changes from baseline in Montgomery-Asberg Depression
      Rating Scale (MADRS), Clinical Global Impression-severity (CGI-S), Clinical
      Global Impression-improvement (CGI-I), 17-Item Hamilton Rating Scale for
      Depression (HAM-D17), Sheehan Disability scale (SDS), and Inventory of Depressive
      Symptomatology Self-Report Scale (IDS-SR), discontinuation due to adverse events,
      and adverse events. Risk ratio (RR) or weight mean difference with 95% confidence
      intervals (CIs) were pooled using a fixed-effects or random-effects model
      according to the heterogeneity among studies. Results: A total of 8 RCTs
      involving 2,260 patients were included in this meta-analysis. Adjunctive
      aripiprazole was associated with a significantly higher remission rate (RR =1.64,
      95% CI: 1.42 to 1.89; P<0.001) and response rate (RR =1.45, 95% CI: 1.13 to 1.87;
      P=0.004) than other treatments. Moreover, adjunctive aripiprazole had greater
      changes in MADRS score, CGI-S score, CGI-I score, HAM-D17 score, SDS score, and
      IDS-SR score. There were more patients treated with adjunctive aripiprazole who
      discontinued their treatments due to adverse events. The incidence of adverse
      events was significantly higher in the adjunctive aripiprazole group than in
      other treatment groups. Conclusion: The adjunctive aripiprazole showed benefits
      in improving the response rate, remission rate, and the quality of life in
      patients with TRD. However, clinicians should interpret these findings with
      caution due to the evidence of potential treatment-related side effects.

PMID- 29445285
TI  - The effect of exercise on cancer-related fatigue in cancer survivors: a
      systematic review and meta-analysis.
AB  - Objective: The objective of the study was to conduct systematic review and meta
      analysis to establish the effect of exercise interventions on cancer-related
      fatigue (CRF) in cancer survivors, compared to non-exercise intervention
      controls. Methods: Trials published between January 1st 2000 and August 17th 2016
      were included through PubMed database search and search of references. Eligible
      trials compared the effect of an exercise intervention on CRF compared to non
      exercise intervention controls, with CRF as primary outcome and measured by
      validated self-report questionnaire, in cancer survivors not receiving palliative
      care. We evaluated risk of bias of individual trials following Cochrane Quality
      criteria. We performed a random-effects meta-analysis in the low risk of bias
      trials with intervention type, exercise intensity, adherence, and cancer type as
      moderators, and also performed meta-regression analyses and a sensitivity
      analysis including the high risk of bias trials. Results: Out of 274 trials, 11
      met the inclusion criteria, of which six had low risk of bias. Exercise improved
      CRF with large effect size (Cohen's d 0.605, 95% CI 0.235-0.975) with no
      significant difference between types of cancer. Aerobic exercise (Delta=1.009, CI
      0.222-1.797) showed a significantly greater effect than a combination of aerobic
      and resistance exercises (Delta=0.341, CI 0.129-0.552). Moderator and meta
      regression analyses showed high adherence yielding best improvements. Conclusion:
      Exercise has a large effect on CRF in cancer survivors. Aerobic interventions
      with high adherence have the best result.

PMID- 29445286
TI  - Glia maturation factor-beta: a potential therapeutic target in neurodegeneration
      and neuroinflammation.
AB  - Glia maturation factor-beta (GMFB) is considered to be a growth and
      differentiation factor for both glia and neurons. GMFB has been found to be
      upregulated in several neuroinflammation and neurodegeneration conditions. It may
      function by mediating apoptosis and by modulating the expression of superoxide
      dismutase, granulocyte-macrophage colony-stimulating factor, and neurotrophin. In
      this review, we mainly discussed the role of GMFB in several neuroinflammatory
      and neurodegenerative diseases. On review of the literature, we propose that GMFB
      may be a promising therapeutic target for neuroinflammatory and neurodegenerative
      diseases.

PMID- 29445287
TI  - Patient knowledge on stroke risk factors, symptoms and treatment options.
AB  - Background: Public campaigns focus primarily on stroke symptom and risk factor
      knowledge, but patients who correctly recognize stroke symptoms do not
      necessarily know the reason for urgent hospitalization. The aim of this study was
      to explore knowledge on stroke risk factors, symptoms and treatment options among
      acute stroke and transient ischemic attack patients. Methods: This prospective
      study included patients admitted to the stroke unit at the Department of
      Neurology, Akershus University Hospital, Norway. Patients with previous
      cerebrovascular disease, patients receiving thrombolytic treatment and patients
      who were not able to answer the questions in the questionnaire were excluded.
      Patients were asked two closed-ended questions: "Do you believe that stroke is a
      serious disorder?" and "Do you believe that time is of importance for stroke
      treatment?". In addition, patients were asked three open-ended questions where
      they were asked to list as many stroke risk factors, stroke symptoms and stroke
      treatment options as they could. Results: A total of 173 patients were included,
      of whom 158 (91.3%) confirmed that they regarded stroke as a serious disorder and
      148 patients (85.5%) considered time being of importance. In all, 102 patients
      (59.0%) could not name any treatment option. Forty-one patients (23.7%) named one
      or more adequate treatment options, and they were younger (p<0.001) and had
      higher educational level (p<0.001), but had a nonsignificant shorter prehospital
      delay time (p=0.292). Conclusion: The level of stroke treatment knowledge in
      stroke patients seems to be poor. Public campaigns should probably also focus on
      information on treatment options, which may contribute to reduce prehospital
      delay and onset-to-treatment-time.

PMID- 29445288
TI  - Prognostic significance of epidermal growth factor receptor expression in glioma
      patients.
AB  - Purpose: There is a great controversy regarding the prognostic significance of
      epidermal growth factor receptor (EGFR) in glioma patients. The current meta
      analysis was conducted to evaluate the effect of abnormal EGFR expression on
      overall survival in glioma patients. Materials and methods: A comprehensive
      literature search of PubMed, EMBASE, Google Scholar, Web of Science, and Cochrane
      Library was conducted. The combined hazard ratio (HR) and its 95% confidence
      intervals (CIs) were used to evaluate the association between EGFR expression and
      survival in glioma. Results: A total of 476 articles were screened, and 17
      articles containing 1,458 patients were selected. The quality assessment of the
      included studies was performed by the Newcastle-Ottawa Scale. Overexpression of
      EGFR was found to be an indicator of poor prognosis in overall survival in glioma
      patients (HR =1.72, 95% CI 1.32-2.25, P=0.000, random effect) and glioblastoma
      multiforme patients (HR =1.57, 95% CI 1.15-2.14, P=0.004, random effect).
      Subgroup analysis was conducted to explore the source of high heterogeneity.
      Conclusion: This meta-analysis indicated that high expression of EGFR may serve
      as a biomarker for poor prognosis in glioma patients.

PMID- 29445289
TI  - Expression of Nemo-like kinase in cervical squamous cell carcinoma: a
      clinicopathological study.
AB  - Objective: Nemo-like kinase (NLK) has been reported to play different roles in
      tumors. However, the role of NLK in cervical squamous cell carcinoma (CSCC)
      remains unknown. In this study, we explored the clinical significance including
      survival of NLK protein expression in CSCCs. Patients and methods:
      Immunohistochemical method was performed using tissues from 130 patients with
      CSCC. The associations between NLK expression and the clinicopathological factors
      and prognosis of CSCCs were evaluated. Statistical analyses were performed using
      the chi-square test, the multivariate Cox proportional hazard model, and the
      Kaplan-Meier method. Results: Immunohistochemical staining analysis showed that
      NLK was localized predominately in the nucleus of the tumor cells, and increased
      NLK expression was detected in 71 (54.6%) of 130 patients. NLK overexpression
      significantly correlated with higher histological grade (P=0.001),
      vascular/lymphatic invasion (P=0.010), lymph node metastasis (P=0.012), and
      recurrence (P=0.022). Patients with elevated NLK expression had poorer overall
      survival (OS) and disease-free survival (DFS) (P=0.006 and P=0.004, respectively)
      compared with patients with decreased NLK expression. Multivariate Cox analysis
      demonstrated that NLK overexpression was an independent factor for OS and DFS
      (P=0.034 and P=0.025, respectively). Conclusion: NLK may be a valuable biomarker
      for predicting the prognosis of CSCC patients and may serve as a potential target
      for cancer therapy.

PMID- 29445290
TI  - Molecular features of giant-cell carcinoma of the lung: a case report and
      literature review.
AB  - Giant-cell carcinoma of the lung (GCCL) is a rare histological form of poorly
      differentiated non-small-cell lung cancer, which is classified as a subtype of
      pulmonary sarcomatoid carcinomas. In this case report, we describe the case of a
      50-year-old Chinese male who presented with a pulmonary nodule in the right upper
      lobe of his lung. After thoracoscopic lobectomy, a histopathologic diagnosis of
      GCCL was made. He did well postoperatively, showing no local recurrence or distal
      disease in a 7-year follow-up period. Furthermore, for this case, we also
      analyzed 295 tumor-related driver genes with high-throughput sequencing
      technology. We found that treatment using MEK inhibitor, CDK 4/6 inhibitor, and
      TP53 inhibitor may provide a new therapeutic direction for GCCL. Therefore,
      complete tumor excision is the best choice of treatment strategy at the early
      stage of GCCL and gene target therapy may be a new therapeutic option for this
      disease.

PMID- 29445291
TI  - Raptor mediates the antiproliferation of cardamonin by mTORC1 inhibition in SKOV3
      cells.
AB  - Purpose: Cardamonin inhibits the proliferation of SKOV3 cells by suppressing the
      mammalian target of rapamycin complex 1 (mTORC1). However, the mechanism of
      cardamonin on mTORC1 inhibition has not been well demonstrated. The regulatory
      associated protein of TOR (Raptor) is an essential component of mTORC1. Here, we
      investigated the role of Raptor in the mTORC1 inhibition effect of cardamonin in
      SKOV3 cells. Methods: The expression of Raptor was knockdown by small interfering
      RNA (siRNA). The expressions of specific binding proteins of mTORC1 were analyzed
      by Western blotting, and the cell proliferation was detected by methyl thiazolyl
      tetrazolium (MTT) assay. Results: Rapamycin, AZD8055, and cardamonin inhibited
      the activity of mammalian target of rapamycin (mTOR). Different from rapamycin
      and AZD8055, cardamonin suppressed the phosphorylation and protein expression of
      Raptor. Transfected with Raptor siRNA, the mTOR activation and proliferation of
      SKOV3 cells were decreased, and these effects were strengthened by cardamonin in
      Raptor siRNA SKOV3 cells. Cardamonin interfered with the lysosomal colocalization
      of mTOR with lysosomal associated membrane protein 2 (LAMP2), which was also
      hindered by Raptor siRNA. Furthermore, cardamonin strengthened the inhibitory
      effect on the lysosomal localization of mTOR in Raptor siRNA cells. Conclusion:
      Our results suggested that Raptor mainly mediated the inhibition of cardamonin on
      mTORC1 in SKOV3 cells.

PMID- 29445293
TI  - Clinical utility of ustekinumab in Crohn's disease.
AB  - The introduction of anti-tumor necrosis factor (TNF) therapy marked an important
      milestone in the management of moderate-to-severe Crohn's disease (CD). However,
      there remains a pressing demand for alternative therapeutic options for patients
      with primary nonresponse, secondary loss of response, or intolerable side effects
      to conventional treatment and TNF antagonists. Ustekinumab (UST) is a fully human
      IgG1kappa monoclonal antibody that inhibits the p40 subunit shared by the
      proinflammatory cytokines, the interleukin (IL)-12 and -23. This blockade leads
      to dampening of the inflammatory cascade and differentiation of inflammatory T
      cells. The clinical development program for UST in CD includes dose finding Phase
      II (Crohn's Evaluation of Response to Ustekinumab Anti-Interleukin-12/23 for
      Induction [CERTIFI]) and the pivotal Phase III (UNITI) trials that demonstrated
      both the clinical efficacy and safety in anti-TNF-naive and anti-TNF-exposed
      patients. Real-world evidence has further defined the role of UST in CD
      management. In this review, we discuss the mechanism of action of UST, describe
      the results of the randomized controlled trials with this agent, and review the
      real-world efficacy and safety data from observational cohorts. Finally, we
      identify areas of future research in the IL-12/23 inflammatory pathway and
      discuss the positioning of this novel therapeutic option in CD treatment
      algorithms.

PMID- 29445292
TI  - Late-onset asthma: current perspectives.
AB  - Because the pathophysiology of asthma has diverse characteristics, to manage the
      disease effectively, it is important for clinicians to distinguish among the
      clinical phenotypes. Among them, adult-onset asthma, that is, late-onset asthma
      (LOA), is increasing because of the aging of the population. The phenotype of LOA
      is largely divided into two types according to the presence or absence of
      eosinophilic inflammation, T-helper (Th)2- and non-Th2-associated LOA. Especially
      in Th2 LOA related to rhinosinusitis, as pulmonary function at onset is poor and
      asthma exacerbations occur frequently, it is important to detect this phenotype
      in the early phase by using a biomarker of Th2-type inflammation such as
      fractional exhaled nitric oxide (FENO). As non-Th2-LOA is often resistant to
      corticosteroids, this phenotype often requires another treatment strategy such as
      macrolide, diet, or smoking cessation. We often struggle with the management of
      LOA patients due to a lack of evidence; therefore, the elucidation of the
      mechanism of LOA contributes to increased efficiency of diagnosis and treatment
      of LOA. Age-related immune system and structural changes are thought to be
      associated with the pathophysiology of LOA. In the former case, changes in
      inflammatory cell function such as variations in the innate immune response and
      acquisition of autoimmunity or upregulation of oxidative stress are thought to be
      involved in the mechanism. Meanwhile, the latter can also become triggers or
      exacerbating factors of LOA via enhancement of airway hyperresponsiveness,
      decline in lung function, increased air trapping, and reduction in chest wall
      compliance. Therefore, appropriate individualized management in LOA may be
      possible through precisely assessing the pathophysiology based on age-related
      functional changes, including the immune and structural system.

PMID- 29445294
TI  - Anxiety and depression in general practice outpatients: the long-term change
      process.
AB  - Background and objectives: Patients who come for a consultation at a general
      practice clinic as outpatients often suffer from background anxiety and
      depression. The psychological state of such patients can alleviate naturally;
      however, there are cases when these symptoms persist. This study investigated the
      realities and factors behind anxiety/depression becoming prolonged. Methods:
      Participants were 678 adult patients, who came to Department of General Medicine
      at Chiba University Hospital within a 1-year period starting from April 2012 and
      who completed the Hospital Anxiety and Depression Scale (HADS) during their
      initial consultation. Participants whose Anxiety or Depression scores in the
      HADS, or both, were 8 points or higher were defined as being within the
      anxiety/depression group, with all other participants making up the control
      group. A telephone interview was also conducted with participants. Furthermore,
      age, sex, the period from the onset of symptoms to the initial consultation at
      our department, the period from the initial department consultation to the
      telephone survey, and the existence of mental illness at the final department
      diagnosis were investigated. Results: A total of 121 patients (17.8% response
      rate) agreed to the phone survey. The HADS score during the phone survey showed
      that the anxiety/depression group had a significantly higher score than the
      control group. The HADS scores obtained between the initial consultation and
      telephone survey showed a positive correlation. Logistic regression analysis
      extracted "age" and the "continuation of the symptoms during the initial
      consultation" as factors that prolonged anxiety/depression. Conclusion: Anxiety
      and depression in general practice outpatients have the possibility of becoming
      prolonged for an extended period of time. Being aged 65 years or over and showing
      a continuation of symptoms past the initial consultation are the strongest
      factors associated with these prolonged conditions. When patients with anxiety
      and depression exhibit these risk factors, they should be further evaluated for
      treatment.

PMID- 29445295
TI  - The effect of exercise frequency on neuropathic pain and pain-related cellular
      reactions in the spinal cord and midbrain in a rat sciatic nerve injury model.
AB  - Background: Exercise regimens are established methods that can relieve
      neuropathic pain. However, the relationship between frequency and intensity of
      exercise and multiple cellular responses of exercise-induced alleviation of
      neuropathic pain is still unclear. We examined the influence of exercise
      frequency on neuropathic pain and the intracellular responses in a sciatic nerve
      chronic constriction injury (CCI) model. Materials and methods: Rats were
      assigned to four groups as follows: CCI and high-frequency exercise (HFE group),
      CCI and low-frequency exercise (LFE group), CCI and no exercise (No-Ex group),
      and naive animals (control group). Rats ran on a treadmill, at a speed of 20
      m/min, for 30 min, for 5 (HFE) or 3 (LFE) days a week, for a total of 5 weeks.
      The 50% withdrawal threshold was evaluated for mechanical sensitivity. The
      activation of glial cells (microglia and astrocytes), expression of brain-derived
      neurotrophic factor (BDNF) and MU-opioid receptor in the spinal dorsal horn and
      endogenous opioid in the midbrain were examined using immunohistochemistry.
      Opioid receptor antagonists (naloxone) were administered using intraperitoneal
      injection. Results: The development of neuropathic pain was related to the
      activation of glial cells, increased BDNF expression, and downregulation of the
      MU-opioid receptor in the ipsilateral spinal dorsal horn. In the No-Ex group,
      neuropathic pain showed the highest level of mechanical hypersensitivity at 2
      weeks, which improved slightly until 5 weeks after CCI. In both exercise groups,
      the alleviation of neuropathic pain was accelerated through the regulation of
      glial activation, BDNF expression, and the endogenous opioid system. The
      expression of BDNF and endogenous opioid in relation to exercise-induced
      alleviation of neuropathic pain differed in the HFE and LFE groups. The effects
      of exercise-induced alleviation of mechanical hypersensitivity were reversed by
      the administration of naloxone. Conclusion: The LFE and HFE program reduced
      neuropathic pain. Our findings indicated that aerobic exercise-induced alleviated
      neuropathic pain through the regulation of glial cell activation, expression of
      BDNF in the ipsilateral spinal dorsal horn, and the endogenous opioid system.

PMID- 29445296
TI  - The ultrasound-guided retrolaminar block: volume-dependent injectate
      distribution.
AB  - Purpose: The ultrasound-guided retrolaminar block is one of the newer and simpler
      alternatives to the traditional, often technically challenging, paravertebral
      (PV) block. Its feasibility, safety, and efficacy have already been clinically
      demonstrated in patients with multiple rib fractures using higher volumes of
      local anesthetic, when compared with the traditional approach. The primary aim of
      this observational anatomical study was to assess the spread of local anesthetic
      from the retrolaminar injection point to the PV space and its volume dependence.
      Second, we assessed the incidence of epidural and contralateral PV spread in the
      both groups. Methods: Ten fresh porcine cadavers were randomized into 2 groups
      (n=5 each) to receive ultrasound-guided retrolaminar injections at Th4-Th5 level
      with either 10 mL (low-volume group) or 30 mL (high-volume group) of 2% lidocaine
      and methylene blue mixture. After the procedure, the cadavers were dissected and
      frozen. Cross-section cuts (~1 cm thick) were performed to evaluate the injectate
      spread. Results: In the high-volume group, injectate spread from the retrolaminar
      to the PV space was observed in all specimens (5 out of 5; 100%), while in the
      low-volume group, no apparent spread to the PV space was found (0 out of 5; 0%).
      No epidural or contralateral PV spread was observed in any of the specimens.
      Conclusion: Following ultrasound-guided retrolaminar injections in fresh porcine
      cadavers, injectate spread from the retrolaminar tissue plane to the PV space is
      strongly volume dependent, suggesting that, clinically, high local anesthetic
      volumes maybe critical for achieving regional anesthesia and analgesia consistent
      with traditional PV blockade.

PMID- 29445298
TI  - Presence of pain on three or more days of the week is associated with worse
      patient reported outcomes in adults with sickle cell disease.
AB  - While acute episodic pain is the hallmark of sickle cell disease (SCD),
      transition to chronic pain is a major cause of morbidity and impaired quality of
      life. One of the core diagnostic criteria used by Analgesic, Anesthetic, and
      Addiction Clinical Trial Translations Innovations Opportunities and Networks
      American Pain Society Pain Taxonomy (AAPT) to define chronic SCD pain is the
      presence of pain on a "majority of days" in the past 6 months in one or more
      locations. The frequency characteristic of "majority of days" is adapted from the
      criteria of 15 days or more per month, used to define chronic migraine, but there
      are inadequate data to support this cutoff in SCD. Using an existing dataset of
      adults with SCD who completed patient-reported outcomes of pain interference,
      physical functioning, anxiety, depression, and fatigue using the National
      Institutes of Health (NIH) patient-reported outcomes measures information system
      (PROMIS) short-form instruments, we examined the association of the presence of
      pain on 3 or more days per week with patient-reported outcomes of functioning. In
      unadjusted analyses, presence of pain on 3 or more days a week was associated
      with higher median PROMIS scores of pain interference, anxiety, and depression.
      Median PROMIS scores of fatigue and physical function were worse in women
      compared with men in unadjusted analyses. We did not find any difference in
      median PROMIS pain scores between adults aged <=35 years compared with those aged
      >=35 years. In linear regression models, after adjustment for age and sex, the
      presence of pain on 3 or more days a week was found to be associated with worse
      pain interference and anxiety. These data support the clinical relevance of the
      frequency characteristic of pain on a "majority of days" in the definition of
      chronic SCD pain, and provide the rationale for prospective studies to validate
      the clinical definition of chronic pain in SCD.

PMID- 29445297
TI  - Managing severe pain and abuse potential: the potential impact of a new abuse
      deterrent formulation oxycodone/naltrexone extended-release product.
AB  - Proper management of severe pain represents one of the most challenging clinical
      dilemmas. Two equally important goals must be attained: the humanitarian/medical
      goal to relieve suffering and the societal/legal goal to not contribute to the
      drug abuse problem. This is an age-old problem, and the prevailing emphasis
      placed on one or the other goal has resulted in pendulum swings that have
      resulted in either undertreatment of pain or the current epidemic of misuse and
      abuse. In an effort to provide efficacious strong pain relievers (opioids) that
      are more difficult to abuse by the most dangerous routes of administration,
      pharmaceutical companies are developing products in which the opioid is
      manufactured in a formulation that is designed to be tamper resistant. Such a
      product is known as an abuse-deterrent formulation (ADF). ADF opioid products are
      designed to deter or resist abuse by making it difficult to tamper with the
      product and extracting the opioid for inhalation or injection. To date, less than
      a dozen opioid formulations have been approved by the US Food and Drug
      Administration to carry specific ADF labeling, but this number will likely
      increase in the coming years. Most of these products are extended-release
      formulations.

PMID- 29445299
TI  - Choosing wisely after publication of level I evidence in breast cancer
      radiotherapy.
AB  - Background: Recent trials in early-stage breast cancer support hypofractionated
      whole-breast radiotherapy (WBRT) as part of breast-conserving therapy (BCT).
      Evidence also suggests that radiotherapy (RT) omission may be reasonable for some
      patients over 70 years. Among radiation-delivery techniques, intensity-modulated
      RT (IMRT) is more expensive than 3-dimensional conformal RT (3DCRT). Based on
      this evidence, in 2013, the American Society for Radiation Oncology (ASTRO)
      recommended hypofractionated schedules for women aged >=50 years with early-stage
      breast cancer and avoiding routine use of IMRT for WBRT. To assess response to
      level I evidence and adherence to ASTRO recommendations, we evaluated the pattern
      of RT use for early-stage breast cancer at our National Comprehensive Cancer
      Network institution from 2006 to 2008 and 2011 to 2013 and compared the results
      with national trends. Methods: Data from a prospective database were extracted to
      include patients treated with BCT, aged >=50 years, with histologic findings of
      invasive ductal carcinoma, stage T1-T2N0M0, estrogen receptor-positive, and HER2
      normal. We retrospectively reviewed the medical records and estimated costs based
      on 2016 Hospital Outpatient Prospective Payment System (technical fees) and
      Medicare Physician Fee Schedule (professional fees). Results: Among 55 cases from
      2006 to 2008, treatment regimens were 11% hypofractionated, 69% traditional
      schedule, and 20% RT omission (29% of patients were aged >70 years). Among 83
      cases from 2011 to 2013, treatment regimens were 54% hypofractionated, 19%
      traditional schedule, and 27% RT omission (48% of patients were aged >70 years).
      3DCRT was used for all WBRT treatments. Direct medical cost estimates were as
      follows: 15 fractions 3DCRT, $7,197.87; 15 fractions IMRT, $11,232.33; 25
      fractions 3DCRT, $9,731.39; and 25 fractions IMRT, $16,877.45. Conclusion:
      Despite apparent resistance to shorter radiation schedules in the United States,
      we demonstrate that rapid practice change in response to level I evidence is
      feasible. Wider adoption of evidence-based guidelines in early-stage breast
      cancer may substantially lower health care costs and improve convenience for
      patients without sacrificing oncologic outcomes.

PMID- 29445301
TI  - Comparative effectiveness of early-line nab-paclitaxel vs. paclitaxel in patients
      with metastatic breast cancer: a US community-based real-world analysis.
AB  - Background: Real-world analyses of treatments for patients with metastatic breast
      cancer are limited. We evaluated the comparative effectiveness of nab-paclitaxel
      vs. paclitaxel in patients with metastatic breast cancer using data from an
      electronic medical record database from community practices across the USA.
      Methods: We performed a retrospective cohort study using fully de-identified data
      from an independent US electronic medical record platform of patients with
      metastatic breast cancer initiating single-agent nab-paclitaxel or paclitaxel as
      a first- or second-line treatment from December 1, 2010 to October 6, 2014. The
      clinical efficacy objectives were time to treatment discontinuation (TTD) and
      time to next treatment (TTNT). Subgroup analyses were performed in patients with
      2 types of metastatic breast cancer as follows: 1) hormone receptor-positive and
      human epidermal growth factor receptor 2 negative, and 2) triple-negative
      disease. Results: This analysis included 925 patients. Patients receiving nab
      paclitaxel vs. paclitaxel had significantly longer TTD (median 4.2 vs. 2.8
      months, P<0.0001) and TTNT (median 6.0 vs. 4.2 months, P<0.0001); similar
      outcomes were observed for patients with hormone receptor-positive/human
      epidermal growth factor receptor 2 negative disease. Compared with paclitaxel,
      nab-paclitaxel was associated with significantly longer TTD in patients with
      triple-negative disease. nab-Paclitaxel was associated with significantly less
      all-grade neuropathy, anemia, pain, and diarrhea than paclitaxel. Antiemetic and
      antihistamine use were significantly less frequent with nab-paclitaxel vs.
      paclitaxel, whereas use of granulocyte colony-stimulating factor, hydrating
      agents, and bone-directed therapy to decrease skeletal-related events were more
      frequent. Conclusion: nab-Paclitaxel demonstrated improved clinical effectiveness
      compared with paclitaxel when examining TTD and TTNT in patients with metastatic
      breast cancer in a real-world setting.

PMID- 29445300
TI  - Gastric cancer: epidemiology, prevention, classification, and treatment.
AB  - Gastric cancer is the second most common cause of cancer-related deaths in the
      world, the epidemiology of which has changed within last decades. A trend of
      steady decline in gastric cancer incidence rates is the effect of the increased
      standards of hygiene, conscious nutrition, and Helicobacter pylori eradication,
      which together constitute primary prevention. Avoidance of gastric cancer remains
      a priority. However, patients with higher risk should be screened for early
      detection and chemoprevention. Surgical resection enhanced by standardized
      lymphadenectomy remains the gold standard in gastric cancer therapy. This review
      briefly summarizes the most important aspects of gastric cancers, which include
      epidemiology, risk factors, classification, diagnosis, prevention, and treatment.
      The paper is mostly addressed to physicians who are interested in updating the
      state of art concerning gastric carcinoma from easily accessible and credible
      source.

PMID- 29445302
TI  - Anastomotic reinforcement with omentoplasty reduces anastomotic leakage for
      minimally invasive esophagectomy with cervical anastomosis.
AB  - Purpose: Anastomotic leakage is the most feared postoperative complication after
      esophagectomy. Omentoplasty, wrapping the omentum around the alimentary tract
      anastomosis, is thought to decrease the anastomotic leakage rate. The purpose of
      this clinical study is to investigate the use of omentoplasty to reinforce
      cervical esophagogastrostomy after minimally invasive esophagectomy (MIE).
      Patients and methods: In this retrospective study, the data of 160 consecutive
      patients who underwent cervical esophagogastrostomy after MIE between September
      2012 and May 2015 were analyzed, 87 who underwent omentoplasty (group A) and 73
      who did not undergo omentoplasty (group B). The primary outcome was the incidence
      of anastomotic leakage and anastomotic strictures after the operation. Secondary
      outcomes were other complications and mortality rate. Univariate and multivariate
      analysis of variables associated with an increased risk for anastomotic leak was
      performed. Results: The median age was 61 years (range, 37-82 years). The
      anastomotic leakage rates were 4.6% (4/87) in group A and 15.1% (11/73) in group
      B (P = 0.023). There was no statistical significance in anastomotic stricture
      rates between group A (6.9%) and group B (9.6%; P = 0.535). No difference was
      noted in other complications between the groups. There was a trend toward lower
      leak-associated mortality rates for group A (0%) compared with that for group B
      (4.1%). Conclusion: Cervical esophagogastrostomy with omentoplasty is more
      effective than esophagogastrostomy without omentoplasty for the prevention of
      anastomotic leakage in MIE with cervical anastomosis. Omentoplasty could be used
      as an adjunct technique to reduce the incidence of anastomotic leakage in
      cervical esophagogastrostomy following MIE.

PMID- 29445303
TI  - Uncemented three-dimensional-printed prosthetic replacement for giant cell tumor
      of distal radius: a new design of prosthesis and surgical techniques.
AB  - Introduction: Currently, it is challenging to treat giant cell tumor (GCT) of
      distal radius. For Campanacci grade III or recurrent GCTs, en bloc resection has
      been accepted as a better treatment option. Although numerous methods are
      available for reconstruction, all of them have some limitations in joint function
      and complications. In this study, our aims were to treat the GCT of distal radius
      with uncemented three-dimensional (3D)-printed prosthesis and to present and
      evaluate the surgical techniques and short-term outcomes. Methods: Between
      September 2015 and March 2017, 11 patients with distal radius GCTs were treated
      with personalized uncemented 3D-printed prosthesis. The
      preoperative/postoperative pain, range of motion, and grip strengths of all
      patients were evaluated. Oncological results, complications, and degenerative
      changes in the wrist joint were evaluated. Functional outcomes were assessed
      according to the disabilities of the arm, shoulder, and hand (DASH) questionnaire
      and Mayo wrist scoring systems. Results: The average follow-up was 14.45 months
      (range, 8-18 months). There was a significant decrease in the mean postoperative
      visual analog scale score (2.33) compared with the preoperative score (5.22;
      p<0.001). The mean DASH score and Mayo wrist score of the wrist joint function
      were 18.7 and 72, respectively. There was no local recurrence or lung metastasis.
      No complication associated with prosthesis was observed, including aseptic
      loosening, subluxation, and breakage. Joint space narrowing, or disuse
      osteoporosis, was also not found in all cases. Conclusion: En bloc resection and
      reconstruction with a personalized uncemented 3D-printed prosthesis can be
      alternative options to treat Campanacci grade III or recurrent GCTs of distal
      radius and can result in short-term oncologic salvage, good postoperative
      function, and low complication rate. However, a long-term follow-up is required
      to determine the outcome.

PMID- 29445304
TI  - Prevalence of medication errors in primary health care at Bahrain Defence Force
      Hospital - prescription-based study.
AB  - Background: One of the important activities that physicians - particularly
      general practitioners - perform is prescribing. It occurs in most health care
      facilities and especially in primary health care (PHC) settings. Objectives: This
      study aims to determine what types of prescribing errors are made in PHC at
      Bahrain Defence Force (BDF) Hospital, and how common they are. Methods: This was
      a retrospective study of data from PHC at BDF Hospital. The data consisted of 379
      prescriptions randomly selected from the pharmacy between March and May 2013, and
      errors in the prescriptions were classified into five types: major omission,
      minor omission, commission, integration, and skill-related errors. Results: Of
      the total prescriptions, 54.4% (N=206) were given to male patients and 45.6%
      (N=173) to female patients; 24.8% were given to patients under the age of 10
      years. On average, there were 2.6 drugs per prescription. In the prescriptions,
      8.7% of drugs were prescribed by their generic names, and 28% (N=106) of
      prescriptions included an antibiotic. Out of the 379 prescriptions, 228 had an
      error, and 44.3% (N=439) of the 992 prescribed drugs contained errors. The
      proportions of errors were as follows: 9.9% (N=38) were minor omission errors;
      73.6% (N=323) were major omission errors; 9.3% (N=41) were commission errors; and
      17.1% (N=75) were skill-related errors. Conclusion: This study provides awareness
      of the presence of prescription errors and frequency of the different types of
      errors that exist in this hospital. Understanding the different types of errors
      could help future studies explore the causes of specific errors and develop
      interventions to reduce them. Further research should be conducted to understand
      the causes of these errors and demonstrate whether the introduction of electronic
      prescriptions has an effect on patient outcomes.

PMID- 29445305
TI  - Implantation of intracorneal ring segments in pediatric patients: long-term
      follow-up.
AB  - Purpose: To analyze the long-term outcomes of intracorneal ring segments (ICRS)
      implantation for keratoconus management in pediatric patients. Methods:
      Retrospective case series review of the long-term (>5 years) outcomes of
      Intacs(r) ICRS implantation for keratoconus in pediatric patients (age <18 years
      old at the time of surgery) between January 2008 and December 2011 at
      Ophthalmology Department of Hospital de Santo Antonio. Demographic data, follow
      up time, preoperative and postoperative uncorrected visual acuity (UCVA) and best
      corrected visual acuity (BCVA) in decimal scale, and corneal topography were
      evaluated. Statistical analysis was done using SPSS for windows (version 24).
      Significance was set at p<0.0125. Results: Fourteen eyes of 14 patients, with a
      mean age of 15.36 years (range 10-18 years), were included in this study. All
      patients had been diagnosed with keratoconus with reported progression in the 6
      months prior to surgery. Follow-up time was 6.36+/-0.97 years. UCVA and BCVA
      improved after ICRS implantation (p<0.0125). Keratometry (K) minimum (Kmin) and K
      maximum (Kmax) decreased after surgery (p<0.0125). During follow-up, UCVA, BCVA,
      Kmin, and Kmax values ranged, showing a tendency to worsen at the end of follow
      up. However, statistically significant differences were not observed. Conclusion:
      ICRS implantation showed good visual and topographic results in pediatric
      patients. Long-term follow-up suggests that, despite ICRS implantation, there is
      still progression of keratoconus. To the best of our knowledge, there are no
      reports regarding the long-term efficacy of ICRS implantation in pediatric
      patients.

PMID- 29445306
TI  - Repository corticotropin injection in patients with rheumatoid arthritis
      resistant to biologic therapies.
AB  - Introduction: Although synthetic and biologic disease-modifying antirheumatic
      drugs are available, many patients with rheumatoid arthritis have a difficult-to
      control disease and need other treatment options. Repository corticotropin
      injection (RCI) may alleviate symptoms and exacerbations in patients with
      refractory disease. Methods: Nine patients with refractory rheumatoid arthritis
      were included in this study. Patients were maintained on their baseline therapies
      with a minimum of 7.5 mg prednisone daily. RCI was given daily at 40 U for 7
      days. Patients who had an adequate disease response were given 40 U twice weekly
      through Week 12. For patients who had inadequate disease response, the dose was
      increased to 80 U daily for 7 days, followed by 80 U twice weekly through Week
      12. Results: The primary endpoint was >1.2 point reduction in the Disease
      Activity Score 28 using C-reactive protein (DAS28-CRP) at Week 12. Secondary
      endpoints were improvements in Health Assessment Questionnaire-Disease Index and
      Functional Assessment of Chronic Illness Therapy scores. Six of the nine patients
      met the primary endpoint. The average change in DAS28-CRP from baseline to Week
      12 was numerically greater with 40 U than with 80 U RCI. Functional Assessment of
      Chronic Illness Therapy and Health Assessment Questionnaire-Disease Index
      improved as early as Week 1, and the improvements remained throughout treatment.
      Conclusion: There was no association between cortisol levels and low-dose RCI
      response. No serious adverse events occurred. RCI produced a clinically
      meaningful reduction in markers of disease activity, improved health-related
      quality of life, and a favorable safety profile. The response rate to RCI was
      substantial and shows promise in this difficult-to-treat population.

PMID- 29445308
TI  - CPR in medical TV shows: non-health care student perspective.
AB  - Introduction: There are over a dozen medical shows airing on television, many of
      which are during prime time. Researchers have recently become more interested in
      the role of these shows, and the awareness on cardiopulmonary resuscitation.
      Several cases have been reported where a lay person resuscitated a family member
      using medical TV shows as a reference. The purpose of this study is to examine
      and evaluate college students' perception on cardiopulmonary resuscitation and
      when to shock using an automated external defibrillator based on their experience
      of watching medical TV shows. Methods: A total of 170 students (nonmedical major)
      were surveyed in four different colleges in the United States. The survey
      consisted of questions that reflect their perception and knowledge acquired from
      watching medical TV shows. A stepwise regression was used to determine the
      significant predictors of "How often do you watch medical drama TV shows" in
      addition to chi-square analysis for nominal variables. Results: Regression model
      showed significant effect that TV shows did change students' perception
      positively (p<0.001), and they would select shock on asystole as the frequency of
      watching increases (p=0.023). Conclusion: The findings of this study show that
      high percentage of nonmedical college students are influenced significantly by
      medical shows. One particular influence is the false belief about when a shock
      using the automated external defibrillator (AED) is appropriate as it is
      portrayed falsely in most medical shows. This finding raises a concern about how
      these shows portray basic life support, especially when not following American
      Heart Association (AHA) guidelines. We recommend the medical advisors in these
      shows to use AHA guidelines and AHA to expand its expenditures to include medical
      shows to educate the public on the appropriate action to rescue an out-of
      hospital cardiac arrest patient.

PMID- 29445309
TI  - The role of pairing an anesthesiology rotation with the general surgery
      clerkship: positive impact on surgical and perioperative education.
AB  - Background: The use of an anesthesiology rotation in the realm of surgical
      education is not very well studied. Several studies show the importance of an
      anesthesiology rotation in the grand scheme of undergraduate medical education.
      However, its importance in perioperative medicine and surgical education is not
      very well understood. This study attempts to look at this relationship and
      determine whether or not a temporal relationship between this anesthesiology
      rotation and a surgical rotation is important. Methods: I used an online survey
      tool to survey medical students who took the anesthesiology rotation (required
      rotation) in 2014 and 2015 (when rotation was coupled to surgical rotation) and
      compared those data to the data of students who took the rotation in 2016 (when
      the rotation was not coupled to surgery). I asked several questions looking at
      the importance of the anesthesiology rotation to surgical education and to
      perioperative medicine. Results: Having a required anesthesiology rotation
      appears to add value to the general surgery rotation in undergraduate medical
      education. Furthermore, when this rotation is paired with the general surgery
      rotation, it appears that the students learn more about perioperative medicine
      than when the rotation is paired with other "advanced" rotation. Conclusion: The
      pairing of anesthesiology with a general surgery rotation does indeed improve the
      perioperative medicine education and knowledge of students. Students appreciate
      having a week of anesthesiology with the surgical rotation, and they note that it
      adds value to the general surgery rotation.

PMID- 29445310
TI  - Training in emerging advances in chronic hepatitis C infection in Pakistan: the
      Teach - Pak project.
AB  - Purpose: Viral hepatitis B and C represent the primary health challenge
      confronting Asia and Pakistan. With direct-acting antiviral therapy for hepatitis
      C, patients will be treated by general physicians (GPs) and will need training
      through continuing medical education (CME). Blended learning is a combination of
      didactic teaching with online, self-paced learning, and it has not been evaluated
      as a CME tool for general physicians. We aimed to compare the change in
      physician's knowledge about chronic viral hepatitis following a blended learning
      educational program. Methods: Participants enrolled in a 6 week blended learning
      program comprising three modules, each of 2 weeks duration. These were: 1)
      epidemiology and prevention of viral hepatitis; 2) diagnosis and assessment of
      hepatitis; and 3) treatment of hepatitis. Activities were primarily web based
      with some face-to-face interactive sessions. All study material was available on
      the Teach - Pak website. Discussions, questions, and comments were encouraged. An
      overall pre-and postintervention knowledge assessment was performed, in addition
      to individual module assessments. Results: A total of 48 participants completed
      the program; 39 passed (81.25%). The participants were from diverse backgrounds
      with variable previous training. The pass rate rose from 16.1% at the start of
      the program to 81.2% at the conclusion. The mean pretest score was 26.0 (standard
      deviation =4.36), while the mean posttest score was 34.6 (standard deviation
      =5.15), showing an increase in the mean score of 8.56 points. Eighty four percent
      had completed at least one credit hour for CME as compared to those who did not
      pass the posttest (44.4% p-value =0.02). No significant differences in results of
      posttest were observed in the categories of participant's age, years since
      graduation, or years of experience. The participants were satisfied with the
      blended learning mode of teaching. Conclusion: Blended learning is an efficient
      way to impart hepatitis CME to a diverse group of postgraduate physicians.

PMID- 29445307
TI  - Sleep problems during the menopausal transition: prevalence, impact, and
      management challenges.
AB  - A substantial number of women experience sleep difficulties in the approach to
      menopause and beyond, with 26% experiencing severe symptoms that impact daytime
      functioning, qualifying them for a diagnosis of insomnia. Here, we review both
      self-report and polysomnographic evidence for sleep difficulties in the context
      of the menopausal transition, considering severity of sleep complaints and links
      between hot flashes (HFs) and depression with poor sleep. Longitudinal population
      based studies show that sleep difficulties are uniquely linked with menopausal
      stage and changes in follicle-stimulating hormone and estradiol, over and above
      the effects of age. A major contributor to sleep complaints in the context of the
      menopausal transition is HFs, and many, although not all, HFs are linked with
      polysomnographic-defined awakenings, with HF-associated wake time contributing
      significantly to overall wakefulness after sleep onset. Some sleep complaints may
      be comorbid with depressive disorders or attributed to sleep-related breathing or
      movement disorders, which increase in prevalence especially after menopause, and
      for some women, menopause, age, and environmental/behavioral factors may interact
      to disrupt sleep. Considering the unique and multifactorial basis for sleep
      difficulties in women transitioning menopause, we describe clinical assessment
      approaches and management options, including combination treatments, ranging from
      cognitive behavioral therapy for insomnia to hormonal and nonhormonal
      pharmacological options. Emerging studies suggest that the impact of severe
      insomnia symptoms could extend beyond immediate health care usage and quality of
      life issues to long-term mental and physical health, if left untreated in midlife
      women. Appropriate treatment, therefore, has immediate benefit as well as
      advantages for maintaining optimal health in the postmenopausal years.

PMID- 29445311
TI  - Fetal growth restriction in rural Bangladesh: a prospective study.
AB  - Background: Fetal growth restriction (FGR) and low birth weight(LBW) are serious
      public health problems. In developing countries, the incidence of low birth
      weight is predominantly the result of FGR, and both low birth weight and FGR are
      associated with neonatal death and later growth and development. Fetal growth
      charts are important for assessing the size of the fetus during pregnancy. The
      aims of this study were to describe the fetal growth pattern of a population in
      rural Bangladesh where maternal undernutrition is prevalent and to compare the
      timing of FGR in that population with WHO and INTERGROWTH- 21st international
      reference values. Methods: From November 2001 to October 2003, pregnant women
      were recruited in Matlab, a sub district of Bangladesh, and underwent three
      follow-up ultrasound examinations during pregnancy for measurement of the
      parameters of the fetal head, abdomen, and femur. The data were fitted to a
      linear-cubic model, and the derived values were compared with international
      reference values. Results: A total of 2678 singleton pregnancies were included in
      the analyses. The mean (SD) maternal age was 25.9 (5.8) years (range, 14-47
      years). The mean (SD) early pregnancy BMI was 20.1 (2.6) kg/m2, and 27.6% of the
      women were underweight (BMI < 18.5 kg/m2). The growth of the biparietal diameter
      and abdominal circumference was significantly smaller throughout the pregnancy
      than the reference values (P <= 0.05). Moreover, a larger deviation in the growth
      of Bangladeshi fetuses was observed after 28 weeks of gestation when compared
      with the WHO and INTERGROWTH-21st reference fetal growth charts (P <= 0.05).
      After 28 weeks of gestation, the average Bangladesh estimated fetal weight gain
      per week of gestational age was significantly lower than the WHO estimated fetal
      weight by as much as 67.4 g (P <= 0.001). Conclusions: The present population
      based study showed that fetuses were smaller in the third trimester when compared
      with the reference charts. Growth faltering started in the second trimester for
      all the biometric parameters for the head, abdomen, and femur. This finding
      provides more challenges concerning nutritional interventions.

PMID- 29445312
TI  - Treatment of Recurrent or Metastatic Uterine Adenosarcoma.
AB  - Purpose: This study retrospectively evaluated overall survival (OS) by treatment
      of recurrent or metastatic uterine adenosarcoma including surgery, radiation,
      chemotherapy, and hormonal therapy and evaluated OS and progression-free survival
      (PFS) after 1st line systemic chemotherapy. Methods: 78 patients with recurrent
      or metastatic adenosarcoma comprised the study population. The Kaplan-Meier
      method was used to estimate OS and PFS. The log-rank test was performed to test
      the difference in survival between groups. Results: Median OS from diagnosis of
      recurrent or metastatic disease was 1.8 yrs. OS was influenced by pathology on
      recurrence, p=0.035. Median OS differed by surgery for 1st recurrence 26.3 months
      versus 15.1 months. OS was not influenced by chemotherapy, p=0.58, palliative
      radiation, p=0.58, or hormonal therapy, p=0.15. The response rate (CR + PR) per
      RECIST 1.1 for chemotherapy was 31.2% for doxorubicin-based regimens and 14.3%
      for gemcitabine/docetaxel. OS since 1st line chemotherapy was not significantly
      different among chemotherapy regimens. However, the median PFS was superior for
      doxorubicin/ifosfamide (15.4 months) compared to gemcitabine/docetaxel (5.0
      months), platinum-based regimens (5.7 mo), or other doxorubicin-based regimens
      (6.5 months). Conclusion: These results suggest that surgery is an important
      treatment modality for recurrent or metastatic uterine adenosarcoma, and the most
      effective chemotherapeutics are doxorubicin/ifosfamide and gemcitabine/docetaxel.

PMID- 29445313
TI  - Little composite dark matter.
AB  - We examine the dark matter phenomenology of a composite electroweak singlet
      state. This singlet belongs to the Goldstone sector of a well-motivated extension
      of the Littlest Higgs with T-parity. A viable parameter space, consistent with
      the observed dark matter relic abundance as well as with the various collider,
      electroweak precision and dark matter direct detection experimental constraints
      is found for this scenario. T-parity implies a rich LHC phenomenology, which
      forms an interesting interplay between conventional natural SUSY type of signals
      involving third generation quarks and missing energy, from stop-like particle
      production and decay, and composite Higgs type of signals involving third
      generation quarks associated with Higgs and electroweak gauge boson, from vector
      like top-partners production and decay. The composite features of the dark matter
      phenomenology allows the composite singlet to produce the correct relic abundance
      while interacting weakly with the Higgs via the usual Higgs portal coupling
      [Formula: see text], thus evading direct detection.

PMID- 29445314
TI  - Prognostic assessment for patients with cancer and incidental pulmonary embolism.
AB  - Background: An incidental/unsuspected diagnosis of pulmonary embolism (IPE) in
      cancer patients is a frequent occurrence. This single-institution analysis of
      uniformly managed patients investigates short and long-term outcomes and proposes
      a prognostic risk score, aiming to assist clinical decision-making. Methods: Data
      from a prospectively recorded cohort of 234 consecutive cancer patients with IPE
      were analysed. Multivariate logistic regression and the Cox regression survival
      methods were used to identify factors with independent association with early (30
      day, 3-month, 6-month) mortality and survival. Receiver operator characteristic
      analysis (ROC) was used to assess appropriate cut-offs for continuous variables
      and the fitness of prognostic scoring. Results: 30-day, 3-month and 6-month
      mortality was 3.4% (n = 8), 15% (n = 35) and 31% (n = 72) respectively.
      Recurrence during anticoagulation occurred in 2.6% (n = 6) and major haemorrhage
      in 2.1% (n = 5) of the patients. A prognostic score incorporating performance
      status (0 vs 1-2 vs 3-4) and the presence of new or worsening symptoms, with and
      without the consideration of the presence of incurable malignancy, correlated
      with overall survival (p < .001 respectively) as well as early mortality (AUC =
      .821, p = .004 and AUC = .805, p = 0.006, respectively). Conclusion: A simple
      prognostic score incorporating basic oncologic clinical assessment and self
      reported symptomatology could reliably stratify the mortality risk of ambulant
      cancer patients and IPE. Trial registration: Audit registration No. 2013.287,
      Hull and East Yorkshire Hospitals Trust, 29/11/2013.

PMID- 29445315
TI  - Surfaces with Controllable Topography and Chemistry Used as a Template for
      Protein Crystallization.
AB  - Surfaces with controllable topography and chemistry were prepared to act as
      substrates for protein crystallization, in order to investigate the influence of
      these surface properties on the protein crystallization outcome. Three different
      methods were investigated to deposit 1,3,5-tris(10-carboxydecyloxy)benzene (TCDB)
      on a muscovite mica substrate to find the best route for controlled topography.
      Of these three, sublimation worked best. Contact angle measurements revealed that
      the surfaces with short exposure to the TCDB vapor (20 min or less) are
      hydrophilic, while surfaces exposed for 30 min or longer are hydrophobic. The
      hydrophilic surfaces are flat with low steps, while the hydrophobic surfaces
      contain macrosteps. Four model proteins were used for crystallization on the
      surfaces with controlled topography and chemistry. Hen egg white lysozyme
      crystals were less numerous on the surface with macrosteps than on smoother
      surfaces. On the other hand, insulin nucleated faster on the hydrophobic surfaces
      with macrosteps, and therefore, the crystals were more abundant and smaller.
      Bovine serum albumin and talin protein crystals were more numerous on all TCDB
      functionalized surfaces, compared to the reference clean muscovite mica surfaces.
      Overall, this shows that surface topography and chemistry is an important factor
      that partly determines the outcome in a protein crystallization experiment.

PMID- 29445316
TI  - Evaluating the Energetic Driving Force for Cocrystal Formation.
AB  - We present a periodic density functional theory study of the stability of 350
      organic cocrystals relative to their pure single-component structures, the
      largest study of cocrystals yet performed with high-level computational methods.
      Our calculations demonstrate that cocrystals are on average 8 kJ mol-1 more
      stable than their constituent single-component structures and are very rarely
      (<5% of cases) less stable; cocrystallization is almost always a
      thermodynamically favorable process. We consider the variation in stability
      between different categories of systems-hydrogen-bonded, halogen-bonded, and
      weakly bound cocrystals-finding that, contrary to chemical intuition, the
      presence of hydrogen or halogen bond interactions is not necessarily a good
      predictor of stability. Finally, we investigate the correlation of the relative
      stability with simple chemical descriptors: changes in packing efficiency and
      hydrogen bond strength. We find some broad qualitative agreement with chemical
      intuition-more densely packed cocrystals with stronger hydrogen bonding tend to
      be more stable-but the relationship is weak, suggesting that such simple
      descriptors do not capture the complex balance of interactions driving
      cocrystallization. Our conclusions suggest that while cocrystallization is often
      a thermodynamically favorable process, it remains difficult to formulate general
      rules to guide synthesis, highlighting the continued importance of high-level
      computation in predicting and rationalizing such systems.

PMID- 29445317
TI  - Resolving Crystallization Kinetics of GeTe Phase-Change Nanoparticles by
      Ultrafast Calorimetry.
AB  - Chalcogenide-based phase change materials (PCMs) are promising candidates for the
      active element in novel electrical nonvolatile memories and have been applied
      successfully in rewritable optical disks. Nanostructured PCMs are considered as
      the next generation building blocks for their low power consumption, high storage
      density, and fast switching speed. Yet their crystallization kinetics at high
      temperature, the rate-limiting property upon switching, faces great challenges
      due to the short time and length scales involved. Here we present a facile method
      to synthesize highly controlled, ligand-free GeTe nanoparticles, an important
      PCM, with an average diameter under 10 nm. Subsequent crystallization by slow and
      ultrafast rates allows unravelling of the crystallization kinetics, demonstrating
      the breakdown of Arrhenius behavior for the crystallization rate and a fragile-to
      strong transition in the viscosity as well as the overall crystal growth rate for
      the as-deposited GeTe nanoparticles. The obtained results pave the way for
      further development of phase-change memory based on GeTe with sub-lithographic
      sizes.

PMID- 29445318
TI  - Inhibition of the Vapor-Mediated Phase Transition of the High Temperature Form of
      Pyrazinamide.
AB  - Tailor-made additives can prove an effective method to prolong the lifetime of
      metastable forms of pharmaceutical compounds by surface stabilization.
      Pyrazinamide (PZA) is a pharmaceutical compound with four polymorphic forms. The
      high temperature gamma form, which can be produced by spray drying or sublimation
      growth, is metastable at room temperature and transforms within days when
      produced by spray drying, and within several months up to years for single
      crystals produced by sublimation. However, when PZA is cospray dried with 1,3
      dimethylurea (DMU), it has been reported to remain in its gamma form for several
      years. Scanning electron microscopy (SEM) images reveal that the phase transition
      from gamma-PZA to the low temperature forms involves a vapor-mediated
      recrystallization, while the reverse phase transition upon heating is a
      nucleation-and-growth solid-solid phase transition. The lifetime-extending effect
      of DMU on spray-dried PZA has been investigated in more detail and compared with
      high-energy ball milling of sublimation-grown gamma-PZA crystals. Co-ball milling
      of PZA and DMU is found to extend the lifetime of the high temperature form of
      PZA to a few months, while separate ball milling leads to an extension of merely
      a few weeks. DMU acts as an additive that most likely stabilizes the surface of
      gamma-PZA, which would reduce the vapor pressure of PZA, thereby reducing the
      transition rate. Alternatively, DMU could prevent nucleation of low temperature
      forms of PZA.

PMID- 29445319
TI  - Quantifying the uptake of user-written commands over time.
AB  - A major factor in the uptake of new statistical methods is the availability of
      user-friendly software implementations. One attractive feature of Stata is that
      users can write their own commands and release them to other users via
      Statistical Software Components at Boston College. Authors of statistical
      programs do not always get adequate credit, because programs are rarely cited
      properly. There is no obvious measure of a program's impact, but researchers are
      under increasing pressure to demonstrate the impact of their work to funders. In
      addition to encouraging proper citation of software, the number of downloads of a
      user-written package can be regarded as a measure of impact over time. In this
      article, we explain how such information can be accessed for any month from July
      2007 and summarized using the new ssccount command.

PMID- 29445320
TI  - A combined test for a generalized treatment effect in clinical trials with a time
      to-event outcome.
AB  - Most randomized controlled trials with a time-to-event outcome are designed and
      analyzed assuming proportional hazards of the treatment effect. The sample-size
      calculation is based on a log-rank test or the equivalent Cox test.
      Nonproportional hazards are seen increasingly in trials and are recognized as a
      potential threat to the power of the log-rank test. To address the issue, Royston
      and Parmar (2016, BMC Medical Research Methodology 16: 16) devised a new
      "combined test" of the global null hypothesis of identical survival curves in
      each trial arm. The test, which combines the conventional Cox test with a new
      formulation, is based on the maximal standardized difference in restricted mean
      survival time (rmst) between the arms. The test statistic is based on evaluations
      of rmst over several preselected time points. The combined test involves the
      minimum p-value across the Cox and rmst-based tests, appropriately standardized
      to have the correct null distribution. In this article, I outline the combined
      test and introduce a command, stctest, that implements the combined test. I point
      the way to additional tools currently under development for power and sample-size
      calculation for the combined test.

PMID- 29445321
TI  - Gallium-68 Labeled Iron Oxide Nanoparticles Coated with 2,3-Dicarboxypropane-1,1
      diphosphonic Acid as a Potential PET/MR Imaging Agent: A Proof-of-Concept Study.
AB  - The aim of this study was to develop a dual-modality PET/MR imaging probe by
      radiolabeling iron oxide magnetic nanoparticles (IONPs), surface functionalized
      with water soluble stabilizer 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD),
      with the positron emitter Gallium-68. Magnetite nanoparticles (Fe3O4 MNPs) were
      synthesized via coprecipitation method and were stabilized with DPD. The Fe3O4
      DPD MNPs were characterized based on their structure, morphology, size, surface
      charge, and magnetic properties. In vitro cytotoxicity studies showed reduced
      toxicity in normal cells, compared to cancer cells. Fe3O4-DPD MNPs were
      successfully labeled with Gallium-68 at high radiochemical purity (>91%) and
      their stability in human serum and in PBS was demonstrated, along with their
      further characterization on size and magnetic properties. The ex vivo
      biodistribution studies in normal Swiss mice showed high uptake in the liver
      followed by spleen. The acquired PET images were in accordance with the ex vivo
      biodistribution results. Our findings indicate that 68Ga-Fe3O4-DPD MNPs could
      serve as an important diagnostic tool for biomedical imaging.

PMID- 29445322
TI  - The Impact of Novel Radiation Treatment Techniques on Toxicity and Clinical
      Outcomes In Rectal Cancer.
AB  - Purpose of review: Three-dimensional conformal radiation therapy (3DCRT) has been
      the standard technique in the treatment of rectal cancer. The use of new
      radiation treatment technologies such as intensity-modulated radiation therapy
      (IMRT), proton therapy (PT), stereotactic body radiation therapy (SBRT) and
      brachytherapy (BT) has been increasing over the past 10 years. This review will
      highlight the advantages and drawbacks of these techniques. Recent findings:
      IMRT, PT, SBRT and BT achieve a higher target coverage conformity, a higher organ
      at risk sparing and enable dose escalation compared to 3DCRT. Some studies
      suggested a reduction in gastrointestinal and hematologic toxicities and an
      increase in the complete pathologic response rate; however, the clinical benefit
      of these techniques remains controversial. Summary: The results of these new
      techniques seem encouraging despite conclusive data. Further trials are required
      to establish their role in rectal cancer.

PMID- 29445323
TI  - Urine proteomics of primary membranous nephropathy using nanoscale liquid
      chromatography tandem mass spectrometry analysis.
AB  - Background: Primary membranous nephropathy (PMN) is an important cause of
      nephrotic syndrome in adults. Urine proteome may provide important clues of
      pathophysiological mechanisms in PMN. In the current study, we analyzed and
      compared the proteome of urine from patients with PMN and normal controls.
      Methods: We performed two technical replicates (TMT1 and TMT2) to analyze and
      compare the urine proteome from patients with PMN and normal controls by tandem
      mass tag (TMT) technology coupled with nanoscale liquid chromatography tandem
      mass spectrometry analysis (LC-MS/MS). Gene ontology (GO) enrichment analysis was
      performed to analyse general characterization of the proteins. The proteins were
      also matched against the database of Kyoto Encyclopedia of Genes and Genomes
      (KEGG). For validation, Western blot was used to analyze the selected proteins.
      Results: A total of 509 proteins and 411 proteins were identified in TMT1 and
      TMT2, respectively. 249 proteins were both identified in two technical
      replicates. GO analysis and KEGG analysis revealed immunization and coagulation
      were predominantly involved. Among the differential protein, the overexcretion of
      alpha-1-antitrypsin (A1AT) and afamin (AFM) were validated by Western blot
      analysis. Conclusions: Our data showed the important role of immunologic
      mechanism in the development of PMN, and the value of urinary A1AT and AFM in
      biomarker discovery of patients with PMN. The discovery of the overexcretion of
      A1AT and AFM in the urine can help to further elucidate pathogenetic mechanisms
      involved in PMN.

PMID- 29445324
TI  - Delayed Degradation and Impaired Dendritic Delivery of Intron-Lacking EGFP
      Arc/Arg3.1 mRNA in EGFP-Arc Transgenic Mice.
AB  - Arc is a unique immediate early gene (IEG) whose expression is induced as
      synapses are modified during learning. Newly-synthesized Arc mRNA is rapidly
      transported throughout dendrites and localizes near recently activated synapses.
      Arc mRNA levels are regulated by rapid degradation, which is accelerated by
      synaptic activity in a translation-dependent process. One possible mechanism is
      nonsense-mediated mRNA decay (NMD), which depends on the presence of a splice
      junction in the 3'UTR. Here, we test this hypothesis using transgenic mice that
      express EGFP-Arc. Because the transgene was constructed from Arc cDNA, it lacks
      intron structures in the 3'UTR that are present in the endogenous Arc gene. NMD
      depends on the presence of proteins of the exon junction complex (EJC) downstream
      of a stop codon, so EGFP-Arc mRNA should not undergo NMD. Assessment of Arc mRNA
      rundown in the presence of the transcription inhibitor actinomycin-D confirmed
      delayed degradation of EGFP-Arc mRNA. EGFP-Arc mRNA and protein are expressed at
      much higher levels in transgenic mice under basal and activated conditions but
      EGFP-Arc mRNA does not enter dendrites efficiently. In a physiological assay in
      which cycloheximide (CHX) was infused after induction of Arc by seizures, there
      were increases in endogenous Arc mRNA levels consistent with translation
      dependent Arc mRNA decay but this was not seen with EGFP-Arc mRNA. Taken
      together, our results indicate: (1) Arc mRNA degradation occurs via a mechanism
      with characteristics of NMD; (2) rapid dendritic delivery of newly synthesized
      Arc mRNA after induction may depend in part on prior splicing of the 3'UTR.

PMID- 29445325
TI  - Biomarkers of Amyotrophic Lateral Sclerosis: Current Status and Interest of
      Oxysterols and Phytosterols.
AB  - Amyotrophic lateral sclerosis (ALS) is a non-demyelinating neurodegenerative
      disease in adults with motor disorders. Two forms exist: a sporadic form (90% of
      cases) and a family form due to mutations in more than 20 genes including the
      Superoxide dismutase 1, TAR DNA Binding Protein, Fused in Sarcoma, chromosome 9
      open reading frame 72 and VAPB genes. The mechanisms associated with this
      pathology are beginning to be known: oxidative stress, glutamate excitotoxicity,
      protein aggregation, reticulum endoplasmic stress, neuroinflammation, alteration
      of RNA metabolism. In various neurodegenerative diseases, such as Alzheimer's
      disease or multiple sclerosis, the involvement of lipids is increasingly
      suggested based on lipid metabolism modifications. With regard to ALS, research
      has also focused on the possible involvement of lipids. Lipid involvement was
      suggested for clinical arguments where changes in cholesterol and LDL/HDL levels
      were reported with, however, differences in positivity between studies. Since
      lipids are involved in the membrane structure and certain signaling pathways, it
      may be considered to look for oxysterols, mainly 25-hydroxycholesterol and its
      metabolites involved in immune response, or phytosterols to find suitable
      biomarkers for this pathology.

PMID- 29445326
TI  - Structure/Function Studies of the alpha4 Subunit Reveal Evolutionary Loss of a
      GlyR Subtype Involved in Startle and Escape Responses.
AB  - Inhibitory glycine receptors (GlyRs) are pentameric ligand-gated anion channels
      with major roles in startle disease/hyperekplexia (GlyR alpha1), cortical
      neuronal migration/autism spectrum disorder (GlyR alpha2), and inflammatory pain
      sensitization/rhythmic breathing (GlyR alpha3). However, the role of the GlyR
      alpha4 subunit has remained enigmatic, because the corresponding human gene
      (GLRA4) is thought to be a pseudogene due to an in-frame stop codon at position
      390 within the fourth membrane-spanning domain (M4). Despite this, a recent
      genetic study has implicated GLRA4 in intellectual disability, behavioral
      problems and craniofacial anomalies. Analyzing data from sequenced genomes, we
      found that GlyR alpha4 subunit genes are predicted to be intact and functional in
      the majority of vertebrate species-with the exception of humans. Cloning of human
      GlyR alpha4 cDNAs excluded alternative splicing and RNA editing as mechanisms for
      restoring a full-length GlyR alpha4 subunit. Moreover, artificial restoration of
      the missing conserved arginine (R390) in the human cDNA was not sufficient to
      restore GlyR alpha4 function. Further bioinformatic and mutagenesis analysis
      revealed an additional damaging substitution at K59 that ablates human GlyR
      alpha4 function, which is not present in other vertebrate GlyR alpha4 sequences.
      The substitutions K59 and X390 were also present in the genome of an ancient
      Denisovan individual, indicating that GLRA4 has been a pseudogene for at least
      30,000-50,000 years. In artificial synapses, we found that both mouse and gorilla
      alpha4beta GlyRs mediate synaptic currents with unusually slow decay kinetics.
      Lastly, to gain insights into the biological role of GlyR alpha4 function, we
      studied the duplicated genes glra4a and glra4b in zebrafish. While glra4b
      expression is restricted to the retina, using a novel tol2-GAL4FF gene trap line
      (SAIGFF16B), we found that the zebrafish GlyR alpha4a subunit gene (glra4a) is
      strongly expressed in spinal cord and hindbrain commissural neurones. Using gene
      knockdown and a dominant-negative GlyR alpha4aR278Q mutant, we found that GlyR
      alpha4a contributes to touch-evoked escape behaviors in zebrafish. Thus, although
      GlyR alpha4 is unlikely to be involved in human startle responses or disease
      states, this subtype may contribute to escape behaviors in other organisms.

PMID- 29445327
TI  - Missense Gamma-Aminobutyric Acid Receptor Polymorphisms Are Associated with
      Reaction Time, Motor Time, and Ethanol Effects in Vivo.
AB  - Background: The Gamma-aminobutyric acid type A receptor (GABA-A receptor) is
      affected by ethanol concentrations equivalent to those reached during social
      drinking. At these concentrations, ethanol usually causes impairment in reaction
      and motor times in most, but not all, individuals. Objectives: To study the
      effect of GABA-A receptor variability in motor and reaction times, and the effect
      of low ethanol doses. Methods: Two hundred and fifty healthy subjects received
      one single dose of 0.5 g/Kg ethanol per os. Reaction and motor times were
      determined before ethanol challenge (basal), and when participants reached peak
      ethanol concentrations. We analyzed all common missense polymorphisms described
      in the 19 genes coding for the GABA-A receptor subunits by using TaqMan probes.
      Results: The GABRA6 rs4454083 T/C polymorphisms were related to motor times, with
      individuals carrying the C/C genotype having faster motor times, both, at basal
      and at peak ethanol concentrations. The GABRA4 rs2229940 T/T genotype was
      associated to faster reaction times and with lower ethanol effects, determined as
      the difference between basal reaction time and reaction time at peak
      concentrations. All these associations remained significant after correction for
      multiple comparisons. No significant associations were observed for the common
      missense SNPs GABRB3 rs12910925, GABRG2 rs211035, GABRE rs1139916, GABRP
      rs1063310, GABRQ rs3810651, GABRR1 rs12200969 or rs1186902, GABRR2 rs282129, and
      GABRR3 rs832032. Conclusions: This study provides novel information supporting a
      role of missense GABA-A receptor polymorphisms in reaction time, motor time and
      effects of low ethanol doses in vivo.

PMID- 29445328
TI  - Hippocampal Atrophy Following Subarachnoid Hemorrhage Correlates with Disruption
      of Astrocyte Morphology and Capillary Coverage by AQP4.
AB  - Despite successful management of ruptured intracranial aneurysm following
      subarachnoid hemorrhage (SAH), delayed cerebral ischemia (DCI) remains the main
      cause of high mortality and morbidity in patients who survive the initial
      bleeding. Astrocytes play a key role in neurovascular coupling. Therefore,
      changes in the neurovascular unit including astrocytes following SAH may
      contribute to the development of DCI and long-term complications. In this study,
      we characterized morphological changes in hippocampal astrocytes following
      experimental SAH, with special emphasis on glia-vascular cross-talk and
      hippocampal volume changes. Four days after induction of SAH or sham-operation in
      mice, their hippocampal volumes were determined by magnetic resonance imaging
      (MRI) and histological/stereological methods. Glial fibrillary acid protein
      (GFAP) immunostained hippocampal sections were examined by stereological
      techniques to detect differences in astrocyte morphology, and global spatial
      sampling method was used to quantify the length density of Aquaporin-4 (AQP4)
      positive capillaries. Our results indicated that hippocampal volume, as measured
      both by MRI and by histological approaches, was significantly lower in SAH
      animals than in the sham-operated group. Accordingly, in this animal model of
      SAH, hippocampal atrophy existed already at the time of DCI onset in humans. SAH
      induced retraction of GFAP positive astrocyte processes, accompanied by a
      significant reduction in the length density of AQP4 positive capillaries as well
      as narrowing of hippocampal capillaries. Meanwhile, astrocyte volume was higher
      in SAH mice compared with the sham-operated group. Morphological changes in
      hippocampal astrocytes seemingly disrupt glia-vascular interactions early after
      SAH and may contribute to hippocampal atrophy. We speculate that astrocytes and
      astrocyte-capillary interactions may provide targets for the development of
      therapies to improve the prognosis of SAH.

PMID- 29445329
TI  - The Effects of Transcranial Direct Current Stimulation (tDCS) on Psychomotor and
      Visual Perception Functions Related to Driving Skills.
AB  - Objective: It could be demonstrated that anodal transcranial direct current
      stimulation (tDCS) of the left dorsolateral prefrontal cortex (DLPFC) enhances
      accuracy in working memory tasks and reaction time in healthy adults and thus may
      also have an influence on complex everyday tasks like driving a car. However, no
      studies have applied tDCS to psychomotor skills related to a standard driving
      test so far. Methods: 10 female and 5 male healthy adults without any medication
      and history of psychiatric or neurological illness were randomly assigned to two
      groups receiving active and sham stimulation in a double blind, cross-over study
      design. Standardized computerized psychomotor tests according to the German
      guidelines for road and traffic safety were administered at baseline. Then they
      performed the same tests during an anodal or sham tDCS of the left DLPFC in two
      separated sessions. Results: No significant improvements in skills related to
      driving performance like visual perception, stress tolerance, concentration, and
      vigilance could be shown after left anodal prefrontal tDCS. Side effects were low
      and did not differ between active and sham stimulation. Conclusions: The findings
      of our study indicate that left prefrontal tDCS may not alter driving skills
      affording more automated action patterns but as shown in previous studies may
      have an influence on driving behavior requiring executive control processes. This
      however has to be proved in future studies and within greater samples.

PMID- 29445330
TI  - Non-neural Muscle Weakness Has Limited Influence on Complexity of Motor Control
      during Gait.
AB  - Cerebral palsy (CP) and Duchenne muscular dystrophy (DMD) are neuromuscular
      disorders characterized by muscle weakness. Weakness in CP has neural and non
      neural components, whereas in DMD, weakness can be considered as a predominantly
      non-neural problem. Despite the different underlying causes, weakness is a
      constraint for the central nervous system when controlling gait. CP demonstrates
      decreased complexity of motor control during gait from muscle synergy analysis,
      which is reflected by a higher total variance accounted for by one synergy
      (tVAF1). However, it remains unclear if weakness directly contributes to higher
      tVAF1 in CP, or whether altered tVAF1 reflects mainly neural impairments. If
      muscle weakness directly contributes to higher tVAF1, then tVAF1 should also be
      increased in DMD. To examine the etiology of increased tVAF1, muscle activity
      data of gluteus medius, rectus femoris, medial hamstrings, medial gastrocnemius,
      and tibialis anterior were measured at self-selected walking speed, and strength
      data from knee extensors, knee flexors, dorsiflexors and plantar flexors, were
      analyzed in 15 children with CP [median (IQR) age: 8.9 (2.2)], 15 boys with DMD
      [8.7 (3.1)], and 15 typical developing (TD) children [8.6 (2.7)]. We computed
      tVAF1 from 10 concatenated steps with non-negative matrix factorization, and
      compared tVAF1 between the three groups with a Mann-Whiney U-test. Spearman's
      rank correlation coefficients were used to determine if weakness in specific
      muscle groups contributed to altered tVAF1. No significant differences in tVAF1
      were found between DMD [tVAF1: 0.60 (0.07)] and TD children [0.65 (0.07)], while
      tVAF1 was significantly higher in CP [(0.74 (0.09)] than in the other groups
      (both p < 0.005). In CP, weakness in the plantar flexors was related to higher
      tVAF1 (r = -0.72). In DMD, knee extensor weakness related to increased tVAF1 (r =
      -0.50). These results suggest that the non-neural weakness in DMD had limited
      influence on complexity of motor control during gait and that the higher tVAF1 in
      children with CP is mainly related to neural impairments caused by the brain
      lesion.

PMID- 29445331
TI  - Do Event-Related Evoked Potentials Reflect Apathy Tendency and Motivation?
AB  - Apathy is a mental state of diminished motivation. Although the reward system as
      the foundation of the motivation in the human brain has been studied extensively
      with neuroimaging techniques, the electrophysiological correlates of motivation
      and apathy have not been fully explored. Thus, in 14 healthy volunteers, we
      examined whether event-related evoked potentials (ERP) obtained during a simple
      number discrimination task with/without rewards reflected apathy tendency and a
      reward-dependent tendency, which were assessed separately using the apathy scale
      and the temperament and character inventory (TCI). Participants were asked to
      judge the size of a number, and received feedback based on their performance in
      each trial. The P3 amplitudes related to the feedback stimuli increased only in
      the reward condition. Furthermore, the P2 amplitudes related to the negative
      feedback stimuli in the reward condition had a positive correlation with the
      reward-dependent tendency in TCI, whereas the P3 amplitudes related to the
      positive feedback stimuli had a negative correlation with the apathy score. Our
      result suggests that the P2 and P3 ERPs to reward-related feedback stimuli are
      modulated in a distinctive manner by the motivational reward dependence and
      apathy tendency, and thus the current paradigm may be useful for investigating
      the brain activity associated with motivation.

PMID- 29445332
TI  - Motor Unit Action Potential Clustering-Theoretical Consideration for Muscle
      Activation during a Motor Task.
AB  - During dynamic or sustained isometric contractions, bursts of muscle activity
      appear in the electromyography (EMG) signal. Theoretically, these bursts of
      activity likely occur because motor units are constrained to fire temporally
      close to one another and thus the impulses are "clustered" with short delays to
      elicit bursts of muscle activity. The purpose of this study was to investigate
      whether a sequence comprised of "clustered" motor unit action potentials (MUAP)
      can explain spectral and amplitude changes of the EMG during a simulated motor
      task. This question would be difficult to answer experimentally and thus,
      required a model to study this type of muscle activation pattern. To this end, we
      modeled two EMG signals, whereby a single MUAP was either convolved with a
      randomly distributed impulse train (EMG-rand) or a "clustered" sequence of
      impulses (EMG-clust). The clustering occurred in windows lasting 5-100 ms. A
      final mixed signal of EMG-clust and EMG-rand, with ratios (1:1-1:10), was also
      modeled. A ratio of 1:1 would indicate that 50% of MUAP were randomly
      distributed, while 50% of "clustered" MUAP occurred in a given time window (5-100
      ms). The results of the model showed that clustering MUAP caused a downshift in
      the mean power frequency (i.e., ~30 Hz) with the largest shift occurring with a
      cluster window of 10 ms. The mean frequency shift was largest when the ratio of
      EMG-clust to EMG-rand was high. Further, the clustering of MUAP also caused a
      substantial increase in the amplitude of the EMG signal. This model potentially
      explains an activation pattern that changes the EMG spectra during a motor task
      and thus, a potential activation pattern of muscles observed experimentally.
      Changes in EMG measurements during fatiguing conditions are typically attributed
      to slowing of conduction velocity but could, per this model, also result from
      changes of the clustering of MUAP. From a clinical standpoint, this type of
      muscle activation pattern might help describe the pathological movement issues in
      people with Parkinson's disease or essential tremor. Based on our model,
      researchers moving forward should consider how MUAP clustering influences EMG
      spectral and amplitude measurements and how these changes influence movements.

PMID- 29445334
TI  - Post-task Effects on EEG Brain Activity Differ for Various Differential Learning
      and Contextual Interference Protocols.
AB  - A large body of research has shown superior learning rates in variable practice
      compared to repetitive practice. More specifically, this has been demonstrated in
      the contextual interference (CI) and in the differential learning (DL) approach
      that are both representatives of variable practice. Behavioral studies have
      indicate different learning processes in CI and DL. Aim of the present study was
      to examine immediate post-task effects on electroencephalographic (EEG) brain
      activation patterns after CI and DL protocols that reveal underlying neural
      processes at the early stage of motor consolidation. Additionally, we tested two
      DL protocols (gradual DL, chaotic DL) to examine the effect of different degrees
      of stochastic fluctuations within the DL approach with a low degree of
      fluctuations in gradual DL and a high degree of fluctuations in chaotic DL.
      Twenty-two subjects performed badminton serves according to three variable
      practice protocols (CI, gradual DL, chaotic DL), and a repetitive learning
      protocol in a within-subjects design. Spontaneous EEG activity was measured
      before, and immediately after each 20-min practice session from 19 electrodes.
      Results showed distinguishable neural processes after CI, DL, and repetitive
      learning. Increases in EEG theta and alpha power were obtained in somatosensory
      regions (electrodes P3, P7, Pz, P4, P8) in both DL conditions compared to CI, and
      repetitive learning. Increases in theta and alpha activity in motor areas
      (electrodes C3, Cz, C4) were found after chaotic DL compared to gradual DL, and
      CI. Anterior areas (electrodes F3, F7, Fz, F4, F8) showed increased activity in
      the beta and gamma bands after CI. Alpha activity was increased in occipital
      areas (electrodes O1, O2) after repetitive learning. Post-task EEG brain
      activation patterns suggest that DL stimulates the somatosensory and motor
      system, and engages more regions of the cortex than repetitive learning due to a
      tighter stimulation of the motor and somatosensory system during DL practice. CI
      seems to activate specifically executively controlled processing in anterior
      brain areas. We discuss the obtained patterns of post-training EEG traces as
      evidence for different underlying neural processes in CI, DL, and repetitive
      learning at the early stage of motor learning.

PMID- 29445333
TI  - Sleep-Dependent Memory Consolidation and Incremental Sentence Comprehension:
      Computational Dependencies during Language Learning as Revealed by Neuronal
      Oscillations.
AB  - We hypothesize a beneficial influence of sleep on the consolidation of the
      combinatorial mechanisms underlying incremental sentence comprehension. These
      predictions are grounded in recent work examining the effect of sleep on the
      consolidation of linguistic information, which demonstrate that sleep-dependent
      neurophysiological activity consolidates the meaning of novel words and simple
      grammatical rules. However, the sleep-dependent consolidation of sentence-level
      combinatorics has not been studied to date. Here, we propose that dissociable
      aspects of sleep neurophysiology consolidate two different types of combinatory
      mechanisms in human language: sequence-based (order-sensitive) and dependency
      based (order-insensitive) combinatorics. The distinction between the two types of
      combinatorics is motivated both by cross-linguistic considerations and the
      neurobiological underpinnings of human language. Unifying this perspective with
      principles of sleep-dependent memory consolidation, we posit that a function of
      sleep is to optimize the consolidation of sequence-based knowledge (the when) and
      the establishment of semantic schemas of unordered items (the what) that underpin
      cross-linguistic variations in sentence comprehension. This hypothesis builds on
      the proposal that sleep is involved in the construction of predictive codes, a
      unified principle of brain function that supports incremental sentence
      comprehension. Finally, we discuss neurophysiological measures (EEG/MEG) that
      could be used to test these claims, such as the quantification of neuronal
      oscillations, which reflect basic mechanisms of information processing in the
      brain.

PMID- 29445335
TI  - Dual-Tasking in Multiple Sclerosis - Implications for a Cognitive Screening
      Instrument.
AB  - The monitoring of cognitive functions is central to the assessment and
      consecutive management of multiple sclerosis (MS). Though, especially cognitive
      processes that are central to everyday behavior like dual-tasking are often
      neglected. We examined dual-task performance using a psychological-refractory
      period (PRP) task in N = 21 patients and healthy controls and conducted standard
      neuropsychological tests. In dual-tasking, MS patients committed more erroneous
      responses when dual-tasking was difficult. In easier conditions, performance of
      MS patients did not differ to controls. Interestingly, the response times were
      generally not affected by the difficulty of the dual task, showing that the
      deficits observed do not reflect simple motor deficits or deficits in information
      processing speed but point out deficits in executive control functions and
      response selection in particular. Effect sizes were considerably large with
      d~0.80 in mild affected patients and the achieved power was above 99%. There are
      cognitive control and dual tasking deficits in MS that are not attributable to
      simple motor speed deficits. Scaling of the difficulty of dual-tasking makes the
      test applied suitable for a wide variety of MS-patients and may complement
      neuropsychological assessments in clinical care and research setting.

PMID- 29445336
TI  - The Two-Systems Account of Theory of Mind: Testing the Links to Social-
      Perceptual and Cognitive Abilities.
AB  - According to the two-systems account of theory of mind (ToM), understanding
      mental states of others involves both fast social-perceptual processes, as well
      as slower, reflexive cognitive operations (Frith and Frith, 2008; Apperly and
      Butterfill, 2009). To test the respective roles of specific abilities in either
      of these processes we administered 15 experimental procedures to a large sample
      of 343 participants, testing ability in face recognition and holistic perception,
      language, and reasoning. ToM was measured by a set of tasks requiring ability to
      track and to infer complex emotional and mental states of others from faces,
      eyes, spoken language, and prosody. We used structural equation modeling to test
      the relative strengths of a social-perceptual (face processing related) and
      reflexive-cognitive (language and reasoning related) path in predicting ToM
      ability. The two paths accounted for 58% of ToM variance, thus validating a
      general two-systems framework. Testing specific predictor paths revealed language
      and face recognition as strong and significant predictors of ToM. For reasoning,
      there were neither direct nor mediated effects, albeit reasoning was strongly
      associated with language. Holistic face perception also failed to show a direct
      link with ToM ability, while there was a mediated effect via face recognition.
      These results highlight the respective roles of face recognition and language for
      the social brain, and contribute closer empirical specification of the general
      two-systems account.

PMID- 29445339
TI  - Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in
      Growing Piglets as a Model for the Pediatric Population.
AB  - Desmopressin is used to treat primary nocturnal enuresis in children. Over the
      years, various formulations of desmopressin were commercialized of which the
      sublingual melt tablet is preferred in the pediatric population, despite the lack
      of full PK studies in this population. A full PK study was performed in growing
      conventional piglets to evaluate if this juvenile animal model can provide
      supplementary information to complement the information gap in the pediatric
      population. A desmopressin sublingual melt tablet (120 MUg) was administered to
      32 male piglets aged 8 days, 4 weeks, 7 weeks, and 6 months (each group n = 8).
      Population PK (pop-PK) analysis was performed to derive the PK parameters, the
      between- and within-subject variabilities and the effects of covariates.
      Desmopressin demonstrated two-compartmental PK, with a dual, sequential
      absorption process, and linear elimination. Body weight was the only significant
      covariate on clearance and on apparent volume of distribution of the central
      compartment. In human pediatric trials, no double peak in the absorption phase
      was observed in the plasma concentration-time curves, possibly due to the sparse
      sampling strategy applied in those pediatric studies. Therefore, it is
      recommended to perform additional studies, based on the sampling protocol applied
      in the current study.

PMID- 29445337
TI  - Cocaine-Induced Changes in Low-Dimensional Attractors of Local Field Potentials
      in Optogenetic Mice.
AB  - Optogenetically evoked local field potential (LFP) recorded from the medial
      prefrontal cortex (mPFC) of mice during basal conditions and following a systemic
      cocaine administration were analyzed. Blue light stimuli were delivered to mPFC
      through a fiber optic every 2 s and each trial was repeated 100 times. As in the
      previous study, we used a surrogate data method to check that nonlinearity was
      present in the experimental LFPs and only used the last 1.5 s of steady activity
      to measure the LFPs phase resetting induced by the brief 10 ms light stimulus. We
      found that the steady dynamics of the mPFC in response to light stimuli could be
      reconstructed in a three-dimensional phase space with topologically similar "8"
      shaped attractors across different animals. Therefore, cocaine did not change the
      complexity of the recorded nonlinear data compared to the control case. The phase
      space of the reconstructed attractor is determined by the LFP time series and its
      temporally shifted versions by a multiple of some lag time. We also compared the
      change in the attractor shape between cocaine-injected and control using (1)
      dendrogram clustering and (2) Frechet distance. We found about 20% overlap
      between control and cocaine trials when classified using dendrogram method, which
      suggest that it may be possible to describe mathematically both data sets with
      the same model and slightly different model parameters. We also found that the
      lag times are about three times shorter for cocaine trials compared to control.
      As a result, although the phase space trajectories for control and cocaine may
      look similar, their dynamics is significantly different.

PMID- 29445338
TI  - Synaptic Homeostasis and Allostasis in the Dentate Gyrus Caused by Inflammatory
      and Neuropathic Pain Conditions.
AB  - It has been generally accepted that pain can cause imbalance between excitation
      and inhibition (homeostasis) at the synaptic level. However, it remains poorly
      understood how this imbalance (allostasis) develops in the CNS under different
      pain conditions. Here, we analyzed the changes in both excitatory and inhibitory
      synaptic transmission and modulation of the dentate gyrus (DG) under two pain
      conditions with different etiology and duration. First, it was revealed that the
      functions of the input-output (I/O) curves for evoked excitatory postsynaptic
      currents (eEPSCs) following the perforant path (PP) stimulation were gained under
      both acute inflammatory and chronic neuropathic pain conditions relative to the
      controls. However, the functions of I/O curves for the PP-evoked inhibitory
      postsynaptic currents (eIPSCs) differed between the two conditions, namely it was
      greatly gained under inflammatory condition, but was reduced under neuropathic
      condition in reverse. Second, both the frequency and amplitude of miniature IPSCs
      (mIPSCs) were increased under inflammatory condition, however a decrease in
      frequency of mIPSCs was observed under neuropathic condition. Finally, the spike
      discharge of the DG granule cells in response to current injection was
      significantly increased by neuropathic pain condition, however, no different
      change was found between inflammatory pain condition and the control. These
      results provide another line of evidence showing homeostatic and allostatic
      modulation of excitatory synaptic transmission by inhibitory controls under
      different pathological pain conditions, hence implicating use of different
      therapeutic approaches to maintain the homeostasis between excitation and
      inhibition while treating different conditions of pathological pain.

PMID- 29445340
TI  - Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in
      Lung Cancer Cells via the Redox System.
AB  - The pentose phosphate pathway (PPP), which branches from glycolysis, is
      correlated with cancer cell proliferation, survival and senescence. In this
      study, differences in the metabolic profile of the PPP and the redox status of
      human lung carcinoma A549 cells and cisplatin-induced multidrug-resistant
      A549/DDP cells were analyzed and evaluated. The results showed that A549/DDP
      cells exhibited differential PPP-derived metabolic features and redox-related
      molecules. A549/DDP cells exhibited increased expression and enzymatic activity
      of PPP enzyme glucose-6-phosphate dehydrogenase (G6PD). Furthermore, as
      demonstrated by the apoptotic rate, cell viability, and colony formation,
      inhibition of G6PD by siRNA or an inhibitor sensitized A549/DDP cells to
      cisplatin. Additionally, inhibition of G6PD restored the cisplatin sensitivity of
      A549/DDP cells by influencing redox homeostasis. In conclusion, overcoming
      cisplatin resistance through inhibition of G6PD could improve the understanding
      of the mechanisms underlying cisplatin-induced resistance in human lung cancer
      and may provide insights into the therapeutic potential of this treatment to
      combat resistance.

PMID- 29445341
TI  - Celastrol Alleviates Airway Hyperresponsiveness and Inhibits Th17 Responses in
      Obese Asthmatic Mice.
AB  - Severe airway hyperresponsiveness (AHR) is a clinical feature of asthma, which
      has been associated with obesity and has shown a poor response to standard asthma
      treatments such as glucocorticoids. Numerous studies have shown that Interleukin
      (IL)-17 producing CD4+T cells (Th17 cells), which could be inhibited by
      celastrol, is essential in mediating steroid-resistant AHR. The following study
      investigates the impact of celastrol and its mechanism on the regulation of AHR
      in murine model of obesity and asthma. C57BL/6 mice were sensitized by
      intraperitoneal injection of ovalbumin (OVA) on day 1 and 13 starting from 12th
      week, which was followed by aerosol OVA challenge that lasted for 30 min per
      daily for 7 consecutive days starting from 16th week. Diet-induced obesity (DIO)
      mice were fed a high fat diet (HFD) for 16 weeks. Celastrol was administrated
      orally for 7 consecutive days, 30 min before every challenge in DIO-OVA-induced
      mice. Lung functions were analyzed by measuring the airway resistance (Rn) and
      methacholine (MCh) AHR, while H&E staining was used to examine histological
      changes in the lungs. Immunohistochemistry was used to observe IL-17A protein in
      lung tissues; flow cytometry to detect the proportion of Th17 cells in CD4+T
      cells. The concentration of cytokines IL-17A in serum was assessed by
      standardized sandwich ELISA, while the expression of IL-17A mRNA in lung was
      examined by quantitative real-time RT-PCR. Briefly, our data indicated that
      celastrol reduced body mass in DIO-OVA-induced obesity and asthma. Both baseline
      Rn and MCh AHR were significantly lower in celastrol group. Moreover, celastrol
      treatment decreased the frequency of Th17 cell expansion and reduced the
      production of IL-17A in both lung and serum. To sum up, our findings indicated
      that Th17 and its cytokine measured in the spleen and lung were closely
      associated with AHR. In addition, celastrol has shown the ability to suppress AHR
      through Th17 inhibition in obese asthmatic mice.

PMID- 29445342
TI  - The A2B Adenosine Receptor Modulates the Epithelial- Mesenchymal Transition
      through the Balance of cAMP/PKA and MAPK/ERK Pathway Activation in Human
      Epithelial Lung Cells.
AB  - The epithelial-mesenchymal transition (EMT) is a complex process in which cell
      phenotype switches from the epithelial to mesenchymal one. The deregulations of
      this process have been related with the occurrence of different diseases such as
      lung cancer and fibrosis. In the last decade, several efforts have been devoted
      in understanding the mechanisms that trigger and sustain this transition process.
      Adenosine is a purinergic signaling molecule that has been involved in the onset
      and progression of chronic lung diseases and cancer through the A2B adenosine
      receptor subtype activation, too. However, the relationship between A2BAR and EMT
      has not been investigated, yet. Herein, the A2BAR characterization was carried
      out in human epithelial lung cells. Moreover, the effects of receptor activation
      on EMT were investigated in the absence and presence of transforming growth
      factor-beta (TGF-beta1), which has been known to promote the transition. The
      A2BAR activation alone decreased and increased the expression of epithelial
      markers (E-cadherin) and the mesenchymal one (Vimentin, N-cadherin),
      respectively, nevertheless a complete EMT was not observed. Surprisingly, the
      receptor activation counteracted the EMT induced by TGF-beta1. Several
      intracellular pathways regulate the EMT: high levels of cAMP and ERK1/2
      phosphorylation has been demonstrated to counteract and promote the transition,
      respectively. The A2BAR stimulation was able to modulated these two pathways,
      cAMP/PKA and MAPK/ERK, shifting the fine balance toward activation or inhibition
      of EMT. In fact, using a selective PKA inhibitor, which blocks the cAMP pathway,
      the A2BAR-mediated EMT promotion were exacerbated, and conversely the selective
      inhibition of MAPK/ERK counteracted the receptor-induced transition. These
      results highlighted the A2BAR as one of the receptors involved in the modulation
      of EMT process. Nevertheless, its activation is not enough to trigger a complete
      transition, its ability to affect different intracellular pathways could
      represent a mechanism at the basis of EMT maintenance/inhibition based on the
      extracellular microenvironment. Despite further investigations are needed, herein
      for the first time the A2BAR has been related to the EMT process, and therefore
      to the different EMT-related pathologies.

PMID- 29445345
TI  - The Impact of Sex Differences on Odor Identification and Facial Affect
      Recognition in Patients with Schizophrenia Spectrum Disorders.
AB  - Background: Social interactive functions such as facial emotion recognition and
      smell identification have been shown to differ between women and men. However,
      little is known about how these differences are mirrored in patients with
      schizophrenia and how these abilities interact with each other and with other
      clinical variables in patients vs. healthy controls. Methods: Standardized
      instruments were used to assess facial emotion recognition [Facially Expressed
      Emotion Labelling (FEEL)] and smell identification [University of Pennsylvania
      Smell Identification Test (UPSIT)] in 51 patients with schizophrenia spectrum
      disorders and 79 healthy controls; furthermore, working memory functions and
      clinical variables were assessed. Results: In both the univariate and the
      multivariate results, illness showed a significant influence on UPSIT and FEEL.
      The inclusion of age and working memory in the MANOVA resulted in a differential
      effect with sex and working memory as remaining significant factors. Duration of
      illness was correlated with both emotion recognition and smell identification in
      men only, whereas immediate general psychopathology and negative symptoms were
      associated with emotion recognition only in women. Conclusion: Being affected by
      schizophrenia spectrum disorder impacts one's ability to correctly recognize
      facial affects and identify odors. Converging evidence suggests a link between
      the investigated basic and social cognitive abilities in patients with
      schizophrenia spectrum disorders with a strong contribution of working memory and
      differential effects of modulators in women vs. men.

PMID- 29445343
TI  - Medicinal Plants from Near East for Cancer Therapy.
AB  - Background: Cancer is one of the major problems affecting public health
      worldwide. As other cultures, the populations of the Near East rely on medicinal
      herbs and their preparations to fight cancer. Methods: We compiled data derived
      from historical ethnopharmacological information as well as in vitro and in vivo
      results and clinical findings extracted from different literature databases
      including (PubMed, Scopus, Web of Science, and Google Scholar) during the past
      two decades. Results: In this survey, we analyzed the huge amount of data
      available on anticancer ethnopharmacological sources used in the Near East.
      Medicinal herbs are the most dominant ethnopharmacological formula used among
      cancer's patients in the Near East. The data obtained highlight for the first
      time the most commonly used medicinal plants in the Near East area for cancer
      treatment illustrating their importance as natural anticancer agents. The
      literature survey reveals that various Arum species, various Artemisia species,
      Calotropis procera, Citrullus colocynthis, Nigella sativa, Pulicaria crispa,
      various Urtica species, Withania somnifera, and others belong to the most
      frequently used plants among cancer patients in the Near East countries.
      Molecular modes of action that have been investigated for plant extracts and
      isolated compounds from Near East include cell cycle arrest and apoptosis
      induction with participation of major player in these processes such as p53 and
      p21, Bcl-2, Bax, cytochrome c release, poly (ADP-ribose) polymerase cleavage,
      activation of caspases, etc. Conclusion: The ethnopharmacology of the Near East
      was influenced by Arabic and Islamic medicine and might be promising for
      developing new natural and safe anticancer agents. Further research is required
      to elucidate their cellular and molecular mechanisms and to estimate their
      clinical activity.

PMID- 29445347
TI  - Commentary: What more can we learn from early learning theory? The contemporary
      relevance for behaviour change interventions.

PMID- 29445346
TI  - Psychological Shift in Partners of People with Multiple Sclerosis Who Undertake
      Lifestyle Modification: An Interpretive Phenomenological Study.
AB  - : Introduction: Being in an intimate relationship with a person with multiple
      sclerosis (MS) may have a substantial impact on the partner's quality of life.
      Existing research has largely focused on negative impacts of MS for both people
      with MS (PwMS) and their partners and has sampled the population of partners of
      PwMS who have primarily adopted standard medical management only. Modifiable
      lifestyle factors have become increasingly recognized in the management of MS
      symptoms and disease progression. For partners of PwMS who have undertaken
      lifestyle modification as an additional strategy to minimize disease progression,
      the impacts, both positive and negative remain unexplored. This research is
      unique as it focuses on partners of PwMS who have attempted to adopt major
      lifestyle interventions outside of the prevailing paradigm of MS management. Aim:
      To explore and interpret the lived experiences of partners of PwMS who have
      adopted lifestyle modification, to understand partners' attitudes to and
      experiences of the effect of MS and lifestyle modification on their life,
      relationship and view of the future. Method: Design: a qualitative, interpretive,
      phenomenological study using semi-structured interviews. PARTICIPANTS: English
      speaking; aged 18 years or more; in a spousal relationship for 12 months or more
      with a person with MS who had attended a residential lifestyle educational
      intervention and undertaken lifestyle modification. ANALYSIS: Interviews were
      recorded, transcribed verbatim and thematically analyzed using NVivoTM software.
      Results: Twenty-one partners were interviewed. This paper reports one of the
      study's themes, the psychological shift experienced by partners of PwMS. Sub
      themes included adaptation; loss and grief; difficult emotions; reframing, re
      evaluating and re-prioritizing; hope and optimism; empowerment and taking
      control; and self-awareness, greater understanding and personal growth.
      Conclusion: Partners of PwMS who have undertaken lifestyle modification
      experienced a broad range of psychological adjustments. Whilst reflecting the
      potential difficulties that partners of PwMS may experience, this group
      experienced a range of positive psychological changes that add to the literature
      regarding partners' potential experiences and may provide hope for those in
      partnerships with people with MS. This study provides themes to potentially
      inform a quantitative study of a larger population of partners of PwMS.

PMID- 29445344
TI  - Invertebrate Trehalose-6-Phosphate Synthase Gene: Genetic Architecture,
      Biochemistry, Physiological Function, and Potential Applications.
AB  - The non-reducing disaccharide trehalose is widely distributed among various
      organisms. It plays a crucial role as an instant source of energy, being the
      major blood sugar in insects. In addition, it helps countering abiotic stresses.
      Trehalose synthesis in insects and other invertebrates is thought to occur via
      the trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase
      (TPP) pathways. In many insects, the TPP gene has not been identified, whereas
      multiple TPS genes that encode proteins harboring TPS/OtsA and TPP/OtsB conserved
      domains have been found and cloned in the same species. The function of the TPS
      gene in insects and other invertebrates has not been reviewed in depth, and the
      available information is quite fragmented. The present review discusses the
      current understanding of the trehalose synthesis pathway, TPS genetic
      architecture, biochemistry, physiological function, and potential sensitivity to
      insecticides. We note the variability in the number of TPS genes in different
      invertebrate species, consider whether trehalose synthesis may rely only on the
      TPS gene, and discuss the results of in vitro TPS overexpression experiment.
      Tissue expression profile and developmental characteristics of the TPS gene
      indicate that it is important in energy production, growth and development,
      metamorphosis, stress recovery, chitin synthesis, insect flight, and other
      biological processes. We highlight the molecular and biochemical properties of
      insect TPS that make it a suitable target of potential pest control inhibitors.
      The application of trehalose synthesis inhibitors is a promising direction in
      insect pest control because vertebrates do not synthesize trehalose; therefore,
      TPS inhibitors would be relatively safe for humans and higher animals, making
      them ideal insecticidal agents without off-target effects.

PMID- 29445349
TI  - Re-thinking Innovation in Organizations in the Industry 4.0 Scenario: New
      Challenges in a Primary Prevention Perspective.
AB  - In organizations, innovation is considered a relevant aspect of success and long
      term survival. Organizations recognize that innovation contributes to creating
      competitive advantages in a more competitive, challenging and changing labor
      market. The present contribution addresses innovation in organizations in the
      scenario of Industry 4.0, including technological innovation and psychological
      innovation. Innovation is a core concept in this framework to face the challenge
      of globalized and fluid labor market in the 21st century. Reviewing the
      definition of innovation, the article focuses on innovative work behaviors and
      the relative measures. This perspective article also suggests new directions in a
      primary prevention perspective for future research and intervention relative to
      innovation and innovative work behaviors in the organizational context.

PMID- 29445348
TI  - Taekwondo Fighting in Training Does Not Simulate the Affective and Cognitive
      Demands of Competition: Implications for Behavior and Transfer.
AB  - Enhancing practice design is critical to facilitate transfer of learning.
      Considerable research has focused on the role of perceptual information in
      practice simulation, yet has neglected how affect and cognition are shaped by
      practice environments and whether this influences the fidelity of behavior
      (Headrick et al., 2015). This study filled this gap by examining the fidelity of
      individual (cognition, affect, and actions) and interpersonal behavior of 10
      highly skilled Australian Taekwondo athletes fighting in training compared to
      competition. Interpersonal behavior was assessed by tracking location coordinates
      to analyze distance-time coordination tendencies of the fighter-fighter system.
      Individual actions were assessed through notational analysis and approximate
      entropy calculations of coordinate data to quantify the (un)predictability of
      movement displacement. Affect and cognition were assessed with mixed-methods that
      included perceptual scales measuring anxiety, arousal, and mental effort, and
      post-fight video-facilitated confrontational interviews to explore how affect and
      cognitions might differ. Quantitative differences were assessed with mixed models
      and dependent t-tests. Results reveal that individual and interpersonal behavior
      differed between training and competition. In training, individuals attacked less
      (d = 0.81, p < 0.05), initiated attacks from further away (d = -0.20, p < 0.05)
      and displayed more predictable movement trajectories (d = 0.84, p < 0.05). In
      training, fighters had lower anxiety (d = -1.26, p < 0.05), arousal (d = -1.07, p
      < 0.05), and mental effort (d = -0.77, p < 0.05). These results were accompanied
      by changes in interpersonal behavior, with larger interpersonal distances
      generated by the fighter-fighter system in training (d = 0.80, p < 0.05).
      Qualitative data revealed the emergence of cognitions and affect specific to the
      training environment, such as reductions in pressure, arousal, and mental
      challenge. Findings highlight the specificity of performer-environment
      interactions. Fighting in training affords reduced affective and cognitive
      demands and a decrease in action fidelity compared to competition. In addition to
      sampling information, representative practice needs to consider modeling the
      cognitions and affect of competition to enhance transfer.

PMID- 29445350
TI  - Captive Bottlenose Dolphins Do Discriminate Human-Made Sounds Both Underwater and
      in the Air.
AB  - Bottlenose dolphins (Tursiops truncatus) spontaneously emit individual acoustic
      signals that identify them to group members. We tested whether these cetaceans
      could learn artificial individual sound cues played underwater and whether they
      would generalize this learning to airborne sounds. Dolphins are thought to
      perceive only underwater sounds and their training depends largely on visual
      signals. We investigated the behavioral responses of seven dolphins in a group to
      learned human-made individual sound cues, played underwater and in the air.
      Dolphins recognized their own sound cue after hearing it underwater as they
      immediately moved toward the source, whereas when it was airborne they gazed more
      at the source of their own sound cue but did not approach it. We hypothesize that
      they perhaps detected modifications of the sound induced by air or were confused
      by the novelty of the situation, but nevertheless recognized they were being
      "targeted." They did not respond when hearing another group member's cue in
      either situation. This study provides further evidence that dolphins respond to
      individual-specific sounds and that these marine mammals possess some capacity
      for processing airborne acoustic signals.

PMID- 29445351
TI  - Scalar and Ignorance Inferences Are Both Computed Immediately upon Encountering
      the Sentential Connective: The Online Processing of Sentences with Disjunction
      Using the Visual World Paradigm.
AB  - Accounts based on the pragmatic maxim of quantity make different predictions
      about the computation of scalar versus ignorance inferences. These different
      predictions are evaluated in two eye-tracking experiments using a visual world
      paradigm to assess the on-line computation of inferences. The test sentences
      contained disjunction phrases, which engender both kinds of inferences. The first
      experiment documented that both inferences are computed immediately upon
      encountering the disjunctive connective, at nearly identical temporal locations.
      The second experiment was designed to determine whether or not there exists an
      intermediate stage at which the truth of the corresponding conjunction phrase is
      ignored. No such stage was found.

PMID- 29445352
TI  - Preferences for Online and/or Face-to-Face Counseling among University Students
      in Malaysia.
AB  - Increasingly, online counseling is considered to be a cost-effective and highly
      accessible method of providing basic counseling and mental health services. To
      examine the potential of online delivery as a way of increasing overall usage of
      services, this study looked at students' attitudes toward and likelihood of using
      both online and/or face-to-face counseling. A survey was conducted with 409
      students from six universities in Malaysia participating. Approximately 35% of
      participants reported that they would be likely to utilize online counseling
      services but would be unlikely to participate in face-to-face counseling. Based
      on these results, it is suggested that offering online counseling, in addition to
      face-to-face services, could be an effective way for many university counseling
      centers to increase the utilization of their services and thus better serve their
      communities.

PMID- 29445353
TI  - Validation of the Italian Tinnitus Questionnaire Short Form (TQ 12-I) as a Brief
      Test for the Assessment of Tinnitus-Related Distress: Results of a Cross
      Sectional Multicenter-Study.
AB  - Objectives: The use of reliable and valid psychometric tools to assess
      subjectively experienced distress due to tinnitus is broadly recommended. The
      purpose of the study was the validation of the Italian version of Tinnitus
      Questionnaire 12 item short form (TQ 12-I) as a brief test for the assessment of
      patient reported tinnitus-related distress. Design: Cross-sectional multicenter
      questionnaire study. Setting: Tinnitus Center, European Hospital (Rome), the
      Department of Otorhinolaryngology, "Guglielmo da Saliceto" Hospital (Piacenza),
      and the Department of Audiology and Phoniatry, "Mater Domini" University Hospital
      (Catanzaro). Participants: One hundred and forty-three outpatients with tinnitus
      treated at one of the participating medical centers. Main Outcome Measures:
      Tinnitus Questionnaire Short Form (TQ 12-I), compared to the Tinnitus Handicap
      Inventory (THI), Brief Symptom Inventory (BSI), and Short Form (SF-36) Health
      Survey. Results: Our factor analysis revealed a two-factor solution (health
      anxiety, cognitive distress), accounting for 53.5% of the variance. Good internal
      consistency for the total score (alpha = 0.86) and both factors (alpha = 0.79
      0.87) was found. Moderate correlations with the THI (r = 0.65, p < 0.001)
      indicated good convergent validity. Tinnitus distress was further correlated to
      increased psychological distress (r = 0.31, p < 0.001) and reduced emotional well
      being (r = -0.34, p < 0.001). Conclusion: The study clearly showed that the TQ 12
      I is a reliable and valid instrument to assess tinnitus-related distress which
      can be used in clinical practice as well as for research.

PMID- 29445354
TI  - Effects of Acupuncture on the Recovery Outcomes of Stroke Survivors with Shoulder
      Pain: A Systematic Review.
AB  - Background: Poststroke shoulder pain limits stroke survivors' physical
      functioning, impairs their ability to perform daily activities, and compromises
      their quality of life. The use of acupuncture to manage shoulder pain after a
      stroke is believed to free the blockage of energy flow and produce analgesic
      effects, but the evidence is unclear. We therefore conducted a systematic review
      to summarize the current evidence on the effects of acupuncture on the recovery
      outcomes of stroke survivors with shoulder pain. Methods: Fourteen English and
      Chinese databases were searched for data from January 2009 to August 2017. The
      review included adult participants with a clinical diagnosis of ischemic or
      hemorrhagic stroke who had developed shoulder pain and had undergone conventional
      acupuncture, electroacupuncture, fire needle acupuncture, or warm needle
      acupuncture. The participants in the comparison group received the usual stroke
      care only. Results: Twenty-nine randomized controlled trials were included. Most
      studies were assessed as having a substantial risk of bias. Moreover, due to the
      high heterogeneity of the acupuncture therapies examined, pooling the results in
      a meta-analysis was not appropriate. A narrative summary of the results is thus
      presented. The review showed that conventional acupuncture can be associated with
      benefits in reducing pain and edema and improving upper extremity function and
      physical function. The effects of conventional acupuncture on improving shoulder
      range of motion (ROM) are in doubt because this outcome was only examined in two
      trials. Electroacupuncture might be effective in reducing shoulder pain and
      improving upper extremity function, and conclusions on the effects of
      electroacupuncture on edema, shoulder ROM, and physical function cannot be drawn
      due to the limited number of eligible trials. The evidence to support the use of
      fire needle or warm needle acupuncture in stroke survivors with shoulder pain is
      also inconclusive due to the limited number of studies. Conclusion: Although most
      studies reviewed concluded that conventional and electroacupuncture could be
      effective for management of shoulder pain after stroke, the very high potential
      for bias should be considered. Further work in this area is needed that employs
      standardized acupuncture treatment modalities, endpoint assessments, and blinding
      of treatments.

PMID- 29445355
TI  - Plasma Levels of Myonectin But Not Myostatin or Fibroblast-Derived Growth Factor
      21 Are Associated with Insulin Resistance in Adult Humans without Diabetes
      Mellitus.
AB  - Background: Myokines are a group of protein mediators produced by skeletal muscle
      under stress or physical exertion. Even though their discovery and effects in
      cell culture and animal models of disease have elicited great enthusiasm, very
      little is known about their role in human metabolism. We assessed whether plasma
      concentrations of three known myokines [myonectin, myostatin, and fibroblast
      derived growth factor 21 (FGF-21)] would be associated with direct and indirect
      indicators of insulin resistance (IR) in individuals who did not have a diagnosis
      of diabetes. Methods: We studied 81 adults of both sexes comprising a wide range
      of body adiposity and insulin sensitivity. All participants underwent a thorough
      clinical assessment and a 5-point oral glucose tolerance test with calculation of
      multiple IR and insulin sensitivity indices. Twenty-one of them additionally
      underwent a hyperinsulinemic-euglycemic clamp with determination of steady-state
      whole-body insulin-stimulated glucose disposal ("M"). We compared plasma myokine
      concentrations across quartiles of IR indices and clinical IR surrogates, and
      explored the correlation of each myokine with the M-value. Results: Plasma
      myonectin levels increased monotonically across quartiles of the incremental area
      under the insulin curve (higher values indicate more IR) (p-trend = 0.021) and
      decreased monotonically across quartiles of the insulin sensitivity index (ISI -
      higher values indicate less IR) (p-trend = 0.012). After multivariate adjustment
      for other relevant determinants of IR (body mass index, age, and sex), the
      negative association of myonectin with ISI persisted (standardized beta = -0.235,
      p = 0.023). Myostatin was not associated with any clinical IR indicator or direct
      IR index measure. In multivariate analyses, FGF-21 showed a trend toward a
      positive correlation with glucose disposal that did not reach statistical
      significance (standardized beta = 0.476, p = 0.091). Conclusion: The secretion of
      myonectin may constitute an attempt at a compensatory mechanism against IR in
      humans.

PMID- 29445356
TI  - DHEA Supplementation Confers No Additional Benefit to that of Growth Hormone on
      Pregnancy and Live Birth Rates in IVF Patients Categorized as Poor Prognosis.
AB  - Background: In vitro fertilization (IVF) patients receive various adjuvant
      therapies to enhance success rates, but the true benefit is actively debated.
      Growth hormone (GH) and dehydroepiandrosterone (DHEA) supplementation were
      assessed in women undergoing fresh IVF transfer cycles and categorized as poor
      prognosis from five criteria. Methods: Data were retrospectively analyzed from
      626 women undergoing 626 IVF cycles, where they received no adjuvant, GH alone,
      or GH-DHEA in combination. A small group received DHEA alone. The utilization of
      adjuvants was decided between the attending clinician and the patient depending
      on various factors including cost. Results: Despite patients being significantly
      older with lower ovarian reserve, live birth rates were significantly greater
      with GH alone (18.6%) and with GH-DHEA (13.0%) in comparison to those with no
      adjuvant (p < 0.003). No significant difference was observed between the GH
      groups (p = 0.181). Overall, patient age, quality of the transferred embryo, and
      GH treatment were the only significant independent predictors of live birth
      chance. Following adjustment for patient age, antral follicle count, and quality
      of transferred embryo, GH alone and GH-DHEA led to a 7.1-fold and 5.6-fold
      increase in live birth chance, respectively (p < 0.000). Conclusion: These data
      indicated that GH adjuvant may support more live births, particularly in younger
      women, and importantly, the positive effects of GH treatment were still observed
      even if DHEA was also used in combination. However, supplementation with DHEA did
      not indicate any potentiating benefit or modify the effects of GH treatment. Due
      to the retrospective design, and the risk of a selection bias, caution is advised
      in the interpretation of the data.

PMID- 29445357
TI  - Gender Difference in the Association of Early- vs. Late-Onset Type 2 Diabetes
      with Non-Fatal Microvascular Disease in China: A Cross-sectional Study.
AB  - Background: This study aimed to test whether early-onset (defined as <40 years of
      age) type 2 diabetes mellitus (T2DM) imparted different risks of microvascular
      disease to Chinese men and women. Methods: 222,537 Chinese patients with T2DM
      were recruited in 630 hospitals from 106 cities in 30 provinces of China in 2012
      using a cross-sectional design. Logistic regression analysis was performed to
      obtain odds ratios (ORs) of male vs. female for diabetic retinopathy (DR) and
      diabetic nephropathy (DN). Additive interaction was used to test whether male
      gender and early-onset T2DM had interactive effects for DR and DN. Results: More
      men than women with T2DM had DN (4.5 vs. 3.0%, P < 0.0001), DR (5.3 vs. 5.1%, P <
      0.0001), and microvascular disease (either DN or DR) (8.4 vs. 7.1%, P < 0.0001).
      After adjustment for age and levels of hospitals, the effect sizes of early-onset
      T2DM for microvascular disease were higher in men than in women, with a 2.67 [95%
      confidence intervals (CI): 2.51-2.85] fold risk in men and a 2.53 (95% CI: 2.35
      2.72) fold risk in women. The risk effect sizes were greatly attenuated by
      further adjusting for diabetes durations and other traditional risk factors, with
      a 1.28 (95% CI: 1.19-1.37) fold risk in men and a 1.07 (95% CI: 0.99-1.16) fold
      risk in women. After adjustment for diabetes durations and other traditional risk
      factors, using women with late-onset T2DM as the reference, co-presence of early
      onset and male gender significantly enhanced the ORs of either early-onset alone
      (1.10, 95% CI: 1.03-1.19) or male gender alone (0.96, 95% CI: 0.93-0.99) to 1.32
      (95% CI: 1.24-1.41), with significant additive interaction. Kaplan-Meier analysis
      showed that in early-onset T2DM, DN developed 5 years earlier in men than in
      women. Conclusion: Early-onset T2DM increased more risk of microvascular
      complications in Chinese men than in women, most of increased risks being
      attributable to longer diabetes durations.

PMID- 29445358
TI  - Editorial: The Roles of GnIH in Reproductive Function and Behavior.

PMID- 29445359
TI  - Composition and Activity of Microbial Communities along the Redox Gradient of an
      Alkaline, Hypersaline, Lake.
AB  - We compared the composition of microbial communities obtained by sequencing 16S
      rRNA gene amplicons with taxonomy derived from metatranscriptomes from the same
      samples. Samples were collected from alkaline, hypersaline Mono Lake, California,
      USA at five depths that captured the major redox zones of the lake during the
      onset of meromixis. The prokaryotic community was dominated by bacteria from the
      phyla Proteobacteria, Firmicutes, and Bacteroidetes, while the picoeukaryotic
      chlorophyte Picocystis dominated the eukaryotes. Most (80%) of the abundant (>1%
      relative abundance) OTUs recovered as amplicons of 16S rRNA genes have been
      reported in previous surveys, indicating that Mono Lake's microbial community has
      remained stable over 12 years that have included periods of regular, annual
      overturn interspersed by episodes of prolonged meromixis that result in extremely
      reducing conditions in bottom water. Metatranscriptomic sequences binned
      predominately to the Gammaproteobacteria genera Thioalkalivibrio (4-13%) and
      Thioalkalimicrobium (0-14%); and to the Firmicutes genera Dethiobacter (0-5%) and
      Clostridium (1-4%), which were also abundant in the 16S rRNA gene amplicon
      libraries. This study provides insight into the taxonomic affiliations of
      transcriptionally active communities of the lake's water column under different
      redox conditions.

PMID- 29445361
TI  - A Quasi-Steady-State Approximation to the Basic Target-Cell-Limited Viral
      Dynamics Model with a Non-Cytopathic Effect.
AB  - Analysis of previously published target-cell limited viral dynamic models for
      pathogens such as HIV, hepatitis, and influenza generally rely on standard
      techniques from dynamical systems theory or numerical simulation. We use a quasi
      steady-state approximation to derive an analytic solution for the model with a
      non-cytopathic effect, that is, when the death rates of uninfected and infected
      cells are equal. The analytic solution provides time evolution values of all
      three compartments of uninfected cells, infected cells, and virus. Results are
      compared with numerical simulation using clinical data for equine infectious
      anemia virus, a retrovirus closely related to HIV, and the utility of the
      analytic solution is discussed.

PMID- 29445360
TI  - The Dynamic Distribution of Small-Tail Han Sheep Microbiota across Different
      Intestinal Segments.
AB  - The sheep intestinal tract is characterized by a diverse microbial ecosystem that
      is vital for the host to digest diet material. The importance of gut microbiota
      (GM) of animals has also been widely acknowledged because of its pivotal roles in
      the health and well-being of animals. However, there are no relevant studies on
      GM of small-tail Han sheep, a superior mutton variety domestic in China. In this
      study, the structure and distribution of gut microflora were studied by high
      throughput sequencing technology. Results showed a significant difference between
      jejunum and cecum, jejunum, and rectum. Meanwhile, the cecum and rectum not only
      display higher species richness but also exhibit higher similarity of the
      bacterial diversity than that of the jejunum based on the results of abundance
      based coverage estimator (ACE), Chao1, and Shannon indexes. Firmicutes and
      Bacteroidetes were the predominant phyla in cecum and rectum, while higher
      relative abundances of Firmicutes and Cyanobacteria were observed in jejunum. At
      the genus level, Bacteroidetes, Ruminococcus, Lactobacillus, Flavonifractor, and
      Clostridium were the dominant genera in the cecum and rectum. An obvious dynamic
      distribution of Lactobacillus is continuously decreasing from the jejunum to the
      cecum, then to the rectum, whereas the result of Bacteroides is completely
      inverse. In addition, this study also found many kinds of bacteria associated
      with the production of volatile fatty acids (VFA) colonized in the large
      intestine. This study is the first to investigate the distribution of intestinal
      flora in small-tail Han sheep. The findings provide an important indication for
      diagnosis and treatment of intestinal diseases in small-tail Han sheep, as well
      as offer a direction for the development of intestinal microecological
      preparations.

PMID- 29445362
TI  - Microbial Flora Associated with the Halophyte-Salsola imbricate and Its
      Biotechnical Potential.
AB  - Halophytes are associated with the intertidal forest ecosystem of Saudi Arabia
      and seemingly have an immense potential for yielding useful and important natural
      products. In this study we have aimed to isolate and characterize the endophytic
      and rhizospheric bacterial communities from the halophyte, Salsola imbricata, In
      addition these bacterial strains were identified and selected strains were
      further studied for bioactive secondary metabolites. At least 168 rhizspheric and
      endophytic bacteria were isolated and of these 22 were active antagonists against
      the oomycetous fungal plant pathogens, Phytophthora capsici and Pythium ultimum.
      Active cultures were mainly identified with molecular techniques (16S r DNA) and
      this revealed 95.7-100% sequence similarities with relevant type strains. These
      microorgansims were grouped into four major classes: Actinobacteria, Firmicutes,
      beta-Proteobacteria, and gamma-Proteobacteria. Production of fungal cell wall
      lytic enzymes was detected mostly in members of Actinobacteria and Firmicutes.
      PCR screening for type I polyketide synthases (PKS-I), type II polyketide
      synthases (PKS-II) and nonribosomal peptide synthetases (NRPS) revealed 13 of the
      22 strains (59%) were positive for at least one of these important biosynthetic
      genes that are known to be involved in the synthesis of important antibiotics.
      Four bacterial strains of Actinobacteria with potential antagonistic activity
      including two rhizobacteria, EA52 (Nocardiopsis sp.), EA58 (Pseudonocardia sp.)
      and two endophytic bacteria Streptomyces sp. (EA65) and Streptomyces sp. (EA67)
      were selected for secondary metabolite analyses using LC-MS. As a result, the
      presence of different bioactive compounds in the culture extracts was detected
      some of which are already reported for their diverse biological activities
      including antibiotics such as Sulfamethoxypyridazine, Sulfamerazine, and
      Dimetridazole. In conclusion, this study provides an insight into antagonistic
      bacterial population especially the Actinobacteria from S. imbricata, producing
      antifungal metabolites of medical significance and characterized taxonomically in
      future.

PMID- 29445363
TI  - Helicobacter pylori Infection Is Not Associated with Non-alcoholic Fatty Liver
      Disease: A Cross-Sectional Study in China.
AB  - Background and Aim:Helicobacter pylori infection has been reported to promote the
      development of a variety of extra-digestive manifestations, including type 2
      diabetes, cardiovascular and liver diseases. Recently, the association between H.
      pylori infection and non-alcoholic fatty liver disease (NAFLD) was also proposed.
      However, evidence from different studies was controversial. We therefore
      performed this study to investigate the relationship between them in a large
      population of apparently healthy subjects in China. Methods: A total of 21,456
      subjects underwent a healthy checkup program were included. H. pylori infection
      was detected by 14C urea breath test (14C-UBT) and NAFLD was diagnosed by
      ultrasonography. Results: Subjects infected with H. pylori had a more unfavorable
      metabolic profile, including higher levels of body mass index (BMI), blood
      pressure, triglycerides (TG) and lower levels of high-density lipoprotein
      cholesterol (HDL-C), as compared with those without H. pylori infection (all P <
      0.05). Moreover, the prevalence rate of NAFLD was significantly increased in
      subjects with H. pylori infection when compared with those without H. pylori in
      women (23.6% vs. 21.5%, P < 0.05), but not in men (46.5% vs. 45.5%, P > 0.05).
      After adjusting for confounding factors including age, sex, BMI, blood pressure
      and lipid profiles, multivariate logistic analysis revealed that H. pylori
      infection was not independently associated with the risk of NAFLD in the total
      population (OR = 0.9, 95% CI = 0.9-1.0, P = 0.097). Also, subgroup analysis
      (stratified by age, sex, BMI, and diabetes status) showed no independent
      association between H. pylori infection and NAFLD. Conclusion: Our data suggests
      that H. pylori infection is not independently associated with the risk of NAFLD
      in apparently healthy subjects.

PMID- 29445364
TI  - Non-specific Effect of Vaccines: Immediate Protection against Respiratory
      Syncytial Virus Infection by a Live Attenuated Influenza Vaccine.
AB  - The non-specific effects (NSEs) of vaccines have been discussed for their
      potential long-term beneficial effects beyond direct protection against a
      specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV) induces
      local innate immune responses that provide a broad range of antiviral immunity.
      Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non
      specific cross-protection against respiratory syncytial virus (RSV). The degree
      of RSV replication was significantly reduced when X-31ca was administered before
      RSV infection without any RSV-specific antibody responses. The vaccination
      induced an immediate release of cytokines and infiltration of leukocytes into the
      respiratory tract, moderating the immune perturbation caused by RSV infection.
      The potency of protection against RSV challenge was significantly reduced in TLR3
      /- TLR7-/- mice, confirming that the TLR3/7 signaling pathways are necessary for
      the observed immediate and short-term protection. The results suggest that CAIVs
      provide short-term, non-specific protection against genetically unrelated
      respiratory pathogens. The additional benefits of CAIVs in mitigating acute
      respiratory infections for which vaccines are not yet available need to be
      assessed in future studies.

PMID- 29445365
TI  - Babesia microti Infection Changes Host Spleen Architecture and Is Cleared by a
      Th1 Immune Response.
AB  - Babesia microti is a malaria-like parasite, which infects ~2000 people annually,
      such that babesiosis is now a notifiable disease in the United States.
      Immunocompetent individuals often remain asymptomatic and are tested only after
      they feel ill. Susceptible C3H/HeJ mice show several human-like disease
      manifestations and are ideal to study pathogenesis of Babesia species. In this
      study, we examined parasitemia of B. microti at different time points and
      assessed its impact on hemoglobin levels in blood, on spleen pathology and
      overall immune response in C3H/HeJ mice. Peak parasitemia of 42.5% was
      immediately followed by diminished hemoglobin level. Parasitemia at 21 days of
      infection was barely detectable by microscopy presented 5.7 * 108 to 5.9 * 109B.
      microti DNA copies confirming the sensitivity of our qPCR. We hypothesize that
      qPCR detects DNA released from recently lysed parasites or from extracellular B.
      microti in blood, which are not easily detected in blood smears and might result
      in under-diagnosis of babesiosis in patients. Splenectomized patients have been
      reported to show increased babesiosis severity and result in high morbidity and
      mortality. These results emphasize the importance of splenic immunity in
      resolution of B. microti infection. Splenomegaly in infected mice associated with
      destruction of marginal zone with lysed erythrocytes and released B. microti life
      forms in our experiments support this premise. At conclusion of the experiment at
      21 days post-infection, significant splenic B and T cells depletion and increase
      in macrophages levels were observed in B. microti infected mice suggesting a role
      of macrophage in disease resolution. Infected mice also showed significantly
      higher plasmatic concentration of CD4 Th1 cells secreted cytokines such as IL-2
      and IFN-gamma while cytokines such as IL-4, IL-5, and IL-13 secreted by Th2 cells
      increase was not always significant. Thus, Th1 cells-mediated immunity appears to
      be important in clearance of this intracellular pathogen. Significant increase in
      IL-6 that promotes differentiation of Th17 cells was observed but it resulted in
      only moderate change in IL-17A, IL-17F, IL-21, and IL-22, all secreted by Th17
      cells. A similar immune response to Trypanosoma infection has been reported to
      influence the clearance of this protozoan, and co-infecting pathogen(s).

PMID- 29445366
TI  - The Effect of DNA Extraction Methods on Observed Microbial Communities from
      Fibrous and Liquid Rumen Fractions of Dairy Cows.
AB  - DNA based methods have been widely used to study the complexity of the rumen
      microbiota, and it is well known that the method of DNA extraction is a critical
      step in enabling accurate assessment of this complexity. Rumen fluid (RF) and
      fibrous content (FC) fractions differ substantially in terms of their physical
      nature and associated microorganisms. The aim of this study was therefore to
      assess the effect of four DNA extraction methods (RBB, PBB, FDSS, PQIAmini)
      differing in cell lysis and/or DNA recovery methods on the observed microbial
      diversity in RF and FC fractions using samples from four rumen cannulated dairy
      cows fed 100% grass silage (GS100), 67% GS and 33% maize silage (GS67MS33), 33%
      GS and 67% MS (GS33MS67), or 100% MS (MS100). An ANOVA statistical test was
      applied on DNA quality and yield measurements, and it was found that the DNA
      yield was significantly affected by extraction method (p < 0.001) and fraction (p
      < 0.001). The 260/280 ratio was not affected by extraction (p = 0.08) but was
      affected by fraction (p = 0.03). On the other hand, the 260/230 ratio was
      affected by extraction method (p < 0.001) but not affected by fraction (p = 0.8).
      However, all four extraction procedures yielded DNA suitable for further analysis
      of bacterial, archaeal and anaerobic fungal communities using quantitative PCR
      and pyrosequencing of relevant taxonomic markers. Redundancy analysis (RDA) of
      bacterial 16S rRNA gene sequence data at the family level showed that there was a
      significant effect of rumen fraction (p = 0.012), and that PBB (p = 0.012) and
      FDSS (p = 0.024) also significantly contributed to explaining the observed
      variation in bacterial community composition. Whilst the DNA extraction method
      affected the apparent bacterial community composition, no single extraction
      method could be concluded to be ineffective. No obvious effect of DNA extraction
      method on the anaerobic fungi or archaea was observed, although fraction effects
      were evident for both. In summary, the comprehensive assessment of observed
      communities of bacteria, archaea and anaerobic fungi described here provides
      insight into a rational basis for selecting an optimal methodology to obtain a
      representative picture of the rumen microbiota.

PMID- 29445367
TI  - Microbial Communities and Diversities in Mudflat Sediments Analyzed Using a
      Modified Metatranscriptomic Method.
AB  - Intertidal mudflats are land-sea interaction areas and play important roles in
      global nutrient cycles. However, a comprehensive understanding of microbial
      communities in these mudflats remains elusive. In this study, mudflat sediment
      samples from the Dongtan wetland of Chongming Island, the largest alluvial island
      in the world, were collected. Using a modified metatranscriptomic method, the
      depth-wise distributions of potentially active microbial communities were
      investigated based on small subunit ribosomal RNA (SSU rRNA) sequences. Multiple
      environmental factors were also measured and analyzed in conjunction with the
      prokaryotic composition profiles. A prokaryotic diversity analysis based on the
      metatranscriptome datasets revealed two or threefold higher diversity indices
      (associated with potentially active microbes participating in biogeochemical
      processes in Dongtan) compared with the diversity indices based on 16S rRNA gene
      amplicons. Bacteria were numerically dominant relative to archaea, and the
      potentially active prokaryotic taxa were mostly assigned to the bacterial phyla
      Chloroflexi, Acidobacteria, and Bacteroidetes and the classes Delta- and Gamma
      proteobacteria, along with the archaeal lineages phylum Bathyarchaeota and the
      order Thermoplasmatales. The total nitrogen and carbon content of the sediment
      samples were environmental factors that significantly affected the depth-wise
      distributions of both bacterial and archaeal communities. Furthermore, the
      activity of potentially active taxa (including the prevalent order
      Desulfobacterales and family Anaerolineaceae) appeared to be significantly
      underestimated by PCR-based methods, notably at the DNA level, and indicates that
      using normal PCR amplification of DNA limits the study of potential microbial
      activity. This is the first study of potentially active microbial communities in
      depth-wise sediments from Dongtan. The improved knowledge of microbial
      communities in Dongtan provides a foundation for exploring biogeochemical cycling
      and microbial functions.

PMID- 29445368
TI  - Beneficial Oral Biofilms as Smart Bioactive Interfaces.
AB  - Periodontitis is a very common health problem caused by formation of pathogenic
      bacterial biofilm that triggers inflammation resulting in either reversible
      gingivitis or irreversible periodontal hard and soft tissue damages, leading to
      loss of teeth when left untreated. Commensal bacteria play an important role in
      oral health in many aspects. Mainly by colonizing oral tissues, they (i)
      contribute to maturation of immune response, and (ii) foreclose attachment of
      pathobiont and, therefore, prevent from infection. The main goal of the study was
      to investigate if blocking of receptors on a commensal biofilm can prevent or
      reduce the attachment of pathogenic strains. To do so, biofilm produced by
      commensal Streptococcus sanguinis was treated with whole cell lysate of
      pathobionts Fusobacterium nucleatum or Porphyromonas gingivalis, followed by
      incubation with respective strain(s). The study revealed significant reduction in
      pathobiont adhesion to lysate-treated commensal biofilm. Therefore, adhesion of
      pathobionts onto the lysate-blocked biofilm was hindered; however, not completely
      eliminated supporting the idea that such approach in the oral cavity would
      benefit the production of a well-balanced and healthy bioactive interface.

PMID- 29445369
TI  - Turgor Pressure and Possible Constriction Mechanisms in Bacterial Division.
AB  - Bacterial cytokinesis begins with the assembly of FtsZ into a Z ring at the
      center of the cell. The Z-ring constriction in Gram-negative bacteria may occur
      in an environment where the periplasm and the cytoplasm are isoosmotic, but in
      Gram-positive bacteria the constriction may have to overcome a substantial turgor
      pressure. We address three potential sources of invagination force. (1) FtsZ
      itself may generate force by curved protofilaments bending the attached membrane.
      This is sufficient to constrict liposomes in vitro. However, this force is on the
      order of a few pN, and would not be enough to overcome turgor. (2) Cell wall (CW)
      synthesis may generate force by pushing the plasma membrane from the outside.
      However, this would probably require some kind of Brownian ratchet to separate
      the CW and membrane sufficiently to allow a glycan strand to slip in. The elastic
      element is not obvious. (3) Excess membrane production has the potential to
      contribute significantly to the invagination force. If the excess membrane is
      produced under the CW, it would force the membrane to bleb inward. We propose
      here that a combination of FtsZ pulling from the inside, and excess membrane
      pushing membrane inward may generate a substantial constriction force at the
      division site. This combined force generation mechanism may be sufficient to
      overcome turgor pressure. This would abolish the need for a Brownian ratchet for
      CW growth, and would permit CW to operate by reinforcing the constrictions
      generated by FtsZ and excess membrane.

PMID- 29445370
TI  - Ex Vivo Expanded Human Non-Cytotoxic CD8+CD45RClow/- Tregs Efficiently Delay Skin
      Graft Rejection and GVHD in Humanized Mice.
AB  - Both CD4+ and CD8+ Tregs play a critical role in the control of immune responses
      and immune tolerance; however, our understanding of CD8+ Tregs is limited while
      they are particularly promising for therapeutic application. We report here
      existence of highly suppressive human CD8+CD45RClow/- Tregs expressing Foxp3 and
      producing IFNgamma, IL-10, IL-34, and TGFbeta to mediate their suppressive
      activity. We demonstrate that total CD8+CD45RClow/- Tregs can be efficiently
      expanded in the presence of anti-CD3/28 mAbs, high-dose IL-2 and IL-15 and that
      such expanded Tregs efficiently delay GVHD and human skin transplantation
      rejection in immune humanized mice. Robustly expanded CD8+ Tregs displayed a
      specific gene signature, upregulated cytokines and expansion in the presence of
      rapamycin greatly improved proliferation and suppression. We show that
      CD8+CD45RClow/- Tregs are equivalent to canonical CD4+CD25highCD127low/- Tregs
      for suppression of allogeneic immune responses in vitro. Altogether, our results
      open new perspectives to tolerogenic strategies in human solid organ
      transplantation and GVHD.

PMID- 29445371
TI  - Effects of MicroRNA on Regulatory T Cells and Implications for Adoptive Cellular
      Therapy to Ameliorate Graft-versus-Host Disease.
AB  - Regulatory T cells (Tregs) are key mediators of the immune system. MicroRNAs
      (miRNAs) are a family of ~22 nucleotide non-coding RNAs that are processed from
      longer precursors by the RNases Drosha and Dicer. miRNA regulates protein
      expression posttranscriptionally through mRNA destabilization or translational
      silencing. A critical role for miRNA in Treg function was initially discovered
      when both Dicer and Drosha knockout (KO) mice were found to develop a fatal
      autoimmune disease phenotypically similar to Foxp3 KO mice.

PMID- 29445372
TI  - Robust Phenotypic Activation of Eosinophils during Experimental Toxocara canis
      Infection.
AB  - Eosinophils are multifunctional cells that have cytotoxic proinflammatory
      activities and stimulate CD4+ T-cells in experimental models of allergy and
      parasitic infections. Eosinophils, when exposed to antigens, are activated,
      expressing the CD38/CD69 molecules and exhibited increased expression of major
      histocompatibility complex (MHC-II), CD80 and CD86, suggesting they play a role
      upon Toxocara canis antigen stimulation. In the present study, we evaluated the
      profile of eosinophils using conventional and image flow cytometry upon
      experimental T. canis infection. T. canis antigens induced a robust activation on
      this subset, contributing to the immune responses elicited in the experimental
      model for T. canis-associated visceral larva migrans syndrome. Data analysis
      demonstrated that, during murine T. canis infection, eosinophils from peripheral
      blood, spleen, and bone marrow presented upregulated expression of CD69/MHC
      II/CD80/CD86. As opposed to splenic and bone marrow eosinophils, circulating
      eosinophils had increased expression of activation markers upon T. canis
      infection. The enhanced connectivity between eosinophils and T-cells in T. canis
      infected mice in all three compartments (peripheral blood, spleen, and bone
      marrow) also supports the hypothesis that eosinophils may adopt a role during T.
      canis infection. Moreover, in vitro T. canis antigen stimulation resulted in
      activation and upregulation of co-stimulatory-related molecules by bone marrow
      derived eosinophils. Our findings are evidence of activation and upregulation of
      important activation and co-stimulatory-related molecules in eosinophils and
      suggest a reshape of activation hierarchy toward eosinophils during experimental
      T. canis infection.

PMID- 29445373
TI  - Tissue-Dependent Tumor Microenvironments and Their Impact on Immunotherapy
      Responses.
AB  - Recent advances in cancer immunology have led to a better understanding of the
      role of the tumor microenvironment (TME) in tumor initiation, progression, and
      metastasis. Tumors can occur at many locations within the body and coevolution
      between malignant tumor cells and non-malignant cells sculpts the TME at these
      sites. It has become increasingly clear that there are specific differences of
      the TMEs at different anatomical locations, and these tissue-specific TMEs
      regulate tumor growth, determine metastatic progression, and impact on the
      outcome of therapy responses. Herein, we review the scientific advances in
      understanding tissue-specific TMEs, discuss their impact on immunotherapeutic
      response, and assess the current clinical knowledge in this emerging field. A
      deeper understanding of the tissue-specific TME will help to develop effective
      immunotherapies against tumors and their metastases and assist in predicting
      clinical outcomes.

PMID- 29445374
TI  - The Immunome in Two Inherited Forms of Pulmonary Fibrosis.
AB  - : The immunome (immune cell phenotype, gene expression, and serum cytokines
      profiling) in pulmonary fibrosis is incompletely defined. Studies focusing on
      inherited forms of pulmonary fibrosis provide insights into mechanisms of
      fibrotic lung disease in general. To define the cellular and molecular
      immunologic phenotype in peripheral blood, high-dimensional flow cytometry and
      large-scale gene expression of peripheral blood mononuclear cells and serum
      proteomic multiplex analyses were performed and compared in a cohort with
      familial pulmonary fibrosis (FPF), an autosomal dominant disorder with incomplete
      penetrance; Hermansky-Pudlak syndrome pulmonary fibrosis (HPSPF), a rare
      autosomal recessive disorder; and their unaffected relatives. Our results showed
      high peripheral blood concentrations of activated central memory helper cells in
      patients with FPF. Proportions of CD38+ memory CD27- B-cells, IgA+ memory CD27+ B
      cells, IgM+ and IgD+ B-cells, and CD39+ T helper cells were increased whereas
      those of CD39- T helper cells were reduced in patients affected with either
      familial or HPSPF. Gene expression and serum proteomic analyses revealed
      enrichment of upregulated genes associated with mitosis and cell cycle control in
      circulating mononuclear cells as well as altered levels of several analytes,
      including leptin, cytokines, and growth factors. In conclusion, dysregulation of
      the extra-pulmonary immunome is a phenotypic feature of FPF or HPSPF. Further
      studies investigating the blood immunome are indicated to determine the role of
      immune system dysregulation in the pathogenesis of pulmonary fibrosis. Clinical
      Trial Registration: www.ClinicalTrials.gov, identifiers NCT00968084, NCT01200823,
      NCT00001456, and NCT00084305.

PMID- 29445375
TI  - The Role of Cytochromes P450 in Infection.
AB  - Cytochromes are expressed in many different tissues of the human body. They are
      found mostly in intestinal and hepatic tissues. Cytochromes P450 (CYPs) are
      enzymes that oxidize substances using iron and are able to metabolize a large
      variety of xenobiotic substances. CYP enzymes are linked to a wide array of
      reactions including and O-dealkylation, S-oxidation, epoxidation, and
      hydroxylation. The activity of the typical P450 cytochrome is influenced by a
      variety of factors, such as genus, environment, disease state, herbicide,
      alcohol, and herbal medications. However, diet seems to play a major role. The
      mechanisms of action of dietary chemicals, macro- and micronutrients on specific
      CYP isoenzymes have been extensively studied. Dietary modulation has effects upon
      the metabolism of xenobiotics. Cytochromes harbor intra- or interindividual and
      intra- or interethnic genetic polymorphisms. Bacteria were shown to express CYP
      like genes. The tremendous metabolic activity of the microbiota is associated to
      its abundant pool of CYP enzymes, which catalyze phase I and II reactions in drug
      metabolism. Disease states, intestinal disturbances, aging, environmental toxic
      effects, chemical exposures or nutrition modulate the microbial metabolism of a
      drug before absorption. A plethora of effects exhibited by most of CYP enzymes
      can resemble those of proinflammatory cytokines and IFNs. Moreover, they are
      involved in the initiation and persistence of pathologic pain by directly
      activating sensory neurons and inflammatory cytokines.

PMID- 29445376
TI  - Investigating Relationships between Reproduction, Immune Defenses, and Cortisol
      in Dall Sheep.
AB  - Life-history theory is fundamental to understanding how animals allocate
      resources among survival, development, and reproduction, and among traits within
      these categories. Immediate trade-offs occur within a short span of time and,
      therefore, are more easily detected. Trade-offs, however, can also manifest
      across stages of the life cycle, a phenomenon known as carryover effects. We
      investigated trade-offs on both time scales in two populations of Dall sheep
      (Ovis dalli dalli) in Southcentral Alaska. Specifically, we (i) tested for
      glucocorticoid-mediated carryover effects from the breeding season on
      reproductive success and immune defenses during parturition and (ii) tested for
      trade-offs between immune defenses and reproduction within a season. We observed
      no relationship between cortisol during mating and pregnancy success; however, we
      found marginal support for a negative relationship between maternal cortisol and
      neonate birth weights. Low birth weights, resulting from high maternal cortisol,
      may result in low survival or low fecundity for the neonate later in life, which
      could result in overall population decline. We observed a negative relationship
      between pregnancy and bacterial killing ability, although we observed no
      relationship between pregnancy and haptoglobin. Study site affected bactericidal
      capacity and the inflammatory response, indicating the influence of external
      factors on immune responses, although we could not test hypotheses about the
      cause of those differences. This study helps advance our understanding of the
      plasticity and complexity of the immune system and provides insights into the how
      individual differences in physiology may mediate differences in fitness.

PMID- 29445377
TI  - Mouse Models of Influenza Infection with Circulating Strains to Test Seasonal
      Vaccine Efficacy.
AB  - Influenza virus infection is a significant cause of morbidity and mortality
      worldwide. The surface antigens of influenza virus change over time blunting both
      naturally acquired and vaccine induced adaptive immune protection. Viral
      antigenic drift is a major contributing factor to both the spread and disease
      burden of influenza. The aim of this study was to develop better infection models
      using clinically relevant, influenza strains to test vaccine induced protection.
      CB6F1 mice were infected with a range of influenza viruses and disease,
      inflammation, cell influx, and viral load were characterized after infection.
      Infection with circulating H1N1 and representative influenza B viruses induced a
      dose-dependent disease response; however, a recent seasonal H3N2 virus did not
      cause any disease in mice, even at high titers. Viral infection led to
      recoverable virus, detectable both by plaque assay and RNA quantification after
      infection, and increased upper airway inflammation on day 7 after infection
      comprised largely of CD8 T cells. Having established seasonal infection models,
      mice were immunized with seasonal inactivated vaccine and responses were compared
      to matched and mismatched challenge strains. While the H1N1 subtype strain
      recommended for vaccine use has remained constant in the seven seasons between
      2010 and 2016, the circulating strain of H1N1 influenza (2009 pandemic subtype)
      has drifted both genetically and antigenically since 2009. To investigate the
      effect of this observed drift on vaccine induced protection, mice were immunized
      with antigens from A/California/7/2009 (H1N1) and challenged with H1N1 subtype
      viruses recovered from 2009, 2010, or 2015. Vaccination with A/California/7/2009
      antigens protected against infection with either the 2009 or 2010 strains, but
      was less effective against the 2015 strain. This observed reduction in protection
      suggests that mouse models of influenza virus vaccination and infection can be
      used as an additional tool to predict vaccine efficacy against drift strains.

PMID- 29445378
TI  - Fc-Glycosylation in Human IgG1 and IgG3 Is Similar for Both Total and Anti-Red
      Blood Cell Anti-K Antibodies.
AB  - After albumin, immunoglobulin G (IgG) are the most abundant proteins in human
      serum, with IgG1 and IgG3 being the most abundant subclasses directed against
      protein antigens. The quality of the IgG-Fc-glycosylation has important
      functional consequences, which have been found to be skewed toward low
      fucosylation in some antigen-specific immune responses. This increases the
      affinity to IgG1-Fc-receptor (FcgammaR)IIIa/b and thereby directly affects
      downstream effector functions and disease severity. To date, antigen-specific IgG
      glycosylation have not been analyzed for IgG3. Here, we analyzed 30 pregnant
      women with anti-K alloantibodies from a prospective screening cohort and compared
      the type of Fc-tail glycosylation of total serum- and antigen-specific IgG1 and
      IgG3 using mass spectrometry. Total serum IgG1 and IgG3 Fc-glycoprofiles were
      highly similar. Fc glycosylation of antigen-specific IgG varied greatly between
      individuals, but correlated significantly with each other for IgG1 and IgG3,
      except for bisection. However, although the magnitude of changes in fucosylation
      and galactosylation were similar for both subclasses, this was not the case for
      sialylation levels, which were significantly higher for both total and anti-K
      IgG3. We found that the combination of relative IgG1 and IgG3 Fc-glycosylation
      levels did not improve the prediction of anti-K mediated disease over IgG1 alone.
      In conclusion, Fc-glycosylation profiles of serum- and antigen-specific IgG1 and
      IgG3 are highly similar.

PMID- 29445379
TI  - Contribution of Regulatory T Cells in Nucleotide-Binding Oligomerization Domain 2
      Response to Influenza Virus Infection.
AB  - Influenza A virus (IAV) is recognized to cause severe pulmonary illnesses in
      humans, particularly in elderly and children. One of the features associated with
      IAV infection is an excessive lung inflammation due to an uncontrolled immune
      response. The nucleotide-binding oligomerization domain 2 (NOD2) receptor is
      known to recognize ssRNA viruses such as IAV, but its role in the inflammatory
      process during viral infections remains to be clarified. In a previous report, we
      have shown that activation of NOD2 with muramyl dipeptide (MDP) significantly
      reduces both viral loads and lung inflammation and also improves pulmonary
      function during IAV infection. These findings prompted us to further investigate
      whether NOD2 receptor may contribute to regulate inflammation during viral
      infection. In the present study, we show that administration of MDP to mice
      infected with IAV stimulates the migration of regulatory T (Treg) cells to the
      lungs. Such a presence of Treg cells was also accompanied with a reduction of
      neutrophils in the lungs during IAV infection, which correlated, with a
      significant decrease of Th17 cells. In our model, Treg cell recruitment is
      dependent of CXCL12 and CCL5 chemokines. Moreover, we show that the presence of
      Ly6Clow patrolling monocytes is required for Treg cells mobilization to the lung
      of mice treated with MDP. In fact, following monocyte depletion by administration
      of clodronate liposome, mobilization of Treg cells to the lungs of treated mice
      was found to occur when circulating Ly6Clow monocytes begin to reemerge. In
      addition, we also detected an increased production of TGF-beta, a cytokine
      contributing to Treg activity when blood Ly6Clow monocytes are restored.
      Together, our results demonstrate that MDP treatment can promote an anti
      inflammatory environment through the mobilization of Treg cells to the lung, a
      mechanism that requires the presence of Ly6Clow monocytes during IAV infection.
      Overall, our results suggest that activation of NOD2 receptor could be an
      appealing approach to control pulmonary inflammation in patients infected with
      IAV.

PMID- 29445380
TI  - The Role of Indoleamine-2,3-Dioxygenase in Cancer Development, Diagnostics, and
      Therapy.
AB  - Tumors are composed of abnormally transformed cell types and tissues that differ
      from normal tissues in their genetic and epigenetic makeup, metabolism, and
      immunology. Molecular compounds that modulate the immune response against
      neoplasms offer promising new strategies to combat cancer. Inhibitors targeting
      the indoleamine-2,3-dioxygenase 1 enzyme (IDO1) represent one of the most potent
      therapeutic opportunities to inhibit tumor growth. Herein, we assess the
      biochemical role of IDO1 in tumor metabolism and immune surveillance, and review
      current diagnostic and therapeutic approaches that are intended to increase the
      effectiveness of immunotherapies against highly aggressive and difficult-to-treat
      IDO-expressing cancers.

PMID- 29445382
TI  - Innovative Approaches to Evaluate Sugar Beet Responses to Changes in Sulfate
      Availability.
AB  - In this study, a system based on omics profiling was set-up for sugar beet (Beta
      vulgaris L. subsp. vulgaris) evaluation after changes in sulfate availability.
      Seedlings were grown on sulfate-deprived Hoagland solution. Six days after
      germination, 100 MUM MgSO4 was added to the solution. Root samples were collected
      36 h after treatments. WinRHIZO root-scanning approach was used for the automated
      image analysis of plant root morphology. Inductively Coupled Plasma Spectrometry
      (ICP-OES) and quadrupole-time-of-flight mass spectrometry (Q-TOF) were used for
      ionomic and metabolic analysis, respectively. Nanofluidic real-time PCR
      (OpenArray system) was used for molecular profiling. OpenArray chips were
      designed with TaqMan probes for 53 sugar beet genes putatively involved in
      sulfate nutrition. At morphological level treated seedlings showed significantly
      higher values (P < 0.01) than untreated plants for root traits related to soil
      exploration and nutrient uptake, such as total root length, fine roots length and
      root tips number. ICP-OES, Q-TOF and transcriptomic data revealed changes due to
      sulfate availability in sugar beet samples. Two key results are highlighted in
      sulfate-supplied roots and leaves. Firstly, high expression levels of auxin
      efflux carrier component 1 (PIN) and 5-phosphoribosyl-anthranilate, precursor of
      tryptophan and auxin synthesis, were observed in roots. Secondly, high levels of
      2-Cys peroxiredoxin BAS1, chloroplastic, thioredoxin reductase (NADPH) and
      cysteine synthase, chloroplastic/chromoplastic, O-acetylserine sulfhydrylase,
      involved in protection against oxidative stress and cysteine synthase activity,
      respectively, were observed in leaves. Based on our findings, the combination of
      evaluated omics approaches could become a key system for the evaluation of the
      nutritional status of sugar beet under different nutrient availability
      conditions.

PMID- 29445381
TI  - Proteins of TNF-alpha and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes
      Patients with Microalbuminuria.
AB  - Soluble cytokine receptors may play an important role in development of
      microalbuminuria (MA) in type-1 diabetes (T1D). In this study, we measured 12
      soluble receptors and ligands from TNF-alpha/IL6/IL2 pathways in T1D patients
      with MA (n = 89) and T1D patients without MA (n = 483) participating in the
      PAGODA study. Twelve proteins in the sera from T1D patients with and without MA
      were measured using multiplex Luminex assays. Ten serum proteins (sTNFR1, sTNFR2,
      sIL2Ralpha, MMP2, sgp130, sVCAM1, sIL6R, SAA, CRP, and sICAM1) were significantly
      elevated in T1D patients with MA. After adjusting for age, duration of diabetes,
      and sex in logistic regression, association remained significant for seven
      proteins. MA is associated with increasing concentrations of all 10 proteins,
      with the strongest associations observed for sTNFR1 (OR = 108.3, P < 10-32) and
      sTNFR2 (OR = 65.5, P < 10-37), followed by sIL2Ralpha (OR = 12.9, P < 10-13),
      MMP2 (OR = 5.5, P < 10-6), sgp130 (OR = 5.2, P < 10-3), sIL6R (OR = 4.6, P < 10
      4), and sVCAM1 (OR = 3.3, P < 10-4). We developed a risk score system based on
      the combined odds ratios associated with each quintile for each protein. The risk
      scores cluster MA patients into three subsets, each associated with distinct risk
      for MA attributable to proteins in the TNF-alpha/IL6 pathway (mean OR = 1, 13.5,
      and 126.3 for the three subsets, respectively). Our results suggest that the TNF
      alpha/IL6 pathway is overactive in approximately 40% of the MA patients and
      moderately elevated in the middle 40% of the MA patients. Our results suggest the
      existence of distinct subsets of MA patients identifiable by their serum protein
      profiles.

PMID- 29445383
TI  - Study on Reproductive Biology of Rhododendron longipedicellatum: A Newly
      Discovered and Special Threatened Plant Surviving in Limestone Habitat in
      Southeast Yunnan, China.
AB  - Rhododendron longipedicellatum is a narrow endemic species and a subject of
      urgent demand in the domestic market and overseas. Its fascinating shapes,
      brilliantly gilvous flowers, and unusual flowering time endow this species with
      extremely high ornamental value. However, only five wild populations of R.
      longipedicellatum surviving in limestone habitat have been found through
      elaborate field investigation, and the number of the populations decreases
      further or is even confronted with risk of extinction due to the damage of human
      activities. To enhance the protection and utilization of R. longipedicellatum,
      this study systematically investigated several important aspects of reproductive
      biology, including floral syndrome, pollen viability and stigma receptivity,
      petal color reflectance, breeding system, and pollination biology. The results
      demonstrated that arched styles not only create obvious herkogamy that avoide
      self-pollination, but also effectively reduce rain damage to the intrinsic
      characteristics of the stigma surface secretions, promoting the female fitness of
      R. longipedicellatum in poor weather. Pollen viability maintained a high level
      over the flowering period. The reflectance spectrum of petals had two peaks at
      wavelengths of 360 and 580 nm. Tests of OCI, P/O and artificial pollination all
      indicated that R. longipedicellatum was self-compatible and that the breeding
      system was mixed mating. Geitonogamy mediated by Bombus braccatus was the primary
      pollination route in the natural environment, which suggested that the breeding
      system of R. longipedicellatum might be evolving from selfing to outcrossing. The
      pollination vector of R. longipedicellatum was very specific, in that only B.
      braccatus was confirmed to deliver pollen to the stigmas. Visitation frequency
      was influenced by the activity rhythms and resource requirements of the different
      castes (i.e., sex). B. braccatus workers were the most effective pollinators
      because of higher visitation frequency and more effective contribution to fruit
      production, whereas the presence of B. braccatus males might enhance pollen flow
      within the population to a certain extent. Finally, these findings not only
      provided a reliable theoretical basis for hybridization breeding of R.
      longipedicellatum as parents, but also laid a solid foundation for further
      molecular biology studies to more broadly reveal the mechanisms of its
      endangerment in the future.

PMID- 29445384
TI  - Editorial: Harvesting Plant and Microbial Biodiversity for Sustainably Enhanced
      Food Security.

PMID- 29445385
TI  - Fagopyrum esculentum Alters Its Root Exudation after Amaranthus retroflexus
      Recognition and Suppresses Weed Growth.
AB  - Weed control by crops through growth suppressive root exudates is a promising
      alternative to herbicides. Buckwheat (Fagopyrum esculentum) is known for its weed
      suppression and redroot pigweed (Amaranthus retroflexus) control is probably
      partly due to allelopathic root exudates. This work studies whether other weeds
      are also suppressed by buckwheat and if the presence of weeds is necessary to
      induce growth repression. Buckwheat and different weeds were co-cultivated in
      soil, separating roots by a mesh allowing to study effects due to diffusion.
      Buckwheat suppressed growth of pigweed, goosefoot and barnyard grass by 53, 42,
      and 77% respectively without physical root interactions, probably through
      allelopathic compounds. Root exudates were obtained from sand cultures of
      buckwheat (BK), pigweed (P), and a buckwheat/pigweed mixed culture (BK-P). BK-P
      root exudates inhibited pigweed root growth by 49%. Characterization of root
      exudates by UHPLC-HRMS and principal component analysis revealed that BK and BK-P
      had a different metabolic profile suggesting that buckwheat changes its root
      exudation in the presence of pigweed indicating heterospecific recognition. Among
      the 15 different markers, which were more abundant in BK-P, tryptophan was
      identified and four others were tentatively identified. Our findings might
      contribute to the selection of crops with weed suppressive effects.

PMID- 29445386
TI  - Editorial: Evolution of Reproductive Organs in Land Plants.

PMID- 29445387
TI  - QTL Mapping in Three Connected Populations Reveals a Set of Consensus Genomic
      Regions for Low Temperature Germination Ability in Zea mays L.
AB  - Improving seed vigor in response to cold stress is an important breeding
      objective in maize that allows early sowing. Using two cold tolerant inbred lines
      220 and P9-10 and two susceptible lines Y1518 and PH4CV, three connected F2:3
      populations were generated for detecting quantitative trait locus (QTL) related
      to seed low-temperature germination ability. At 10 degrees C, two germination
      traits (emergence rate and germination index) were collected from a sand bed and
      three seedling traits (seedling root length, shoot length, and total length) were
      extracted from paper rolls. Significant correlations were found among all traits
      in all populations. Via single-population analysis, 43 QTL were detected with
      explained phenotypic variance of 0.62%~39.44%. Seventeen QTL explained more than
      10% phenotypic variance; of them sixteen (94.12%) inherited favorable alleles
      from the tolerant lines. After constructing a consensus map, three meta-QTL
      (mQTL) were identified to include at least two initial QTL from different
      populations. mQTL1-1 included seven initial QTL for both germination and seedling
      traits; with three explaining more than 30% phenotypic variance. mQTL2-1 and
      mQTL9-1 covered two to three initial QTL. The favorable alleles of the QTL within
      these three mQTL regions were all inherited from the tolerant line 220 and P9-10.
      These results provided a basis for cloning of genes underlying the mQTL regions
      to uncover the molecular mechanisms of maize cold tolerance during germination.

PMID- 29445388
TI  - Starch Hydrolysis and Vessel Occlusion Related to Wilt Symptoms in Olive Stems of
      Susceptible Cultivars Infected by Verticillium dahliae.
AB  - This study investigated starch content, amount of pathogen DNA and density of
      occluded vessels in healthy and Verticillium dahliae infected olive shoots and
      stems. Starch hydrolysis is considered a mechanism to refill xylem vessels that
      suffered cavitation by either, drought conditions or pathogen infections. The
      main objective of this work was to evaluate this mechanism in olive plants
      subjected to V. dahliae infection or to drought conditions, in order to know the
      importance of cavitation in the development of wilting symptoms. In initial
      experiments starch content in the shoots was studied in trees of cultivars
      differing in the level of resistance growing in fields naturally infested with V.
      dahliae. The starch content, esteemed by microscopic observation of stem
      transversal sections stained with lugol, decreased with the level of symptom
      severity. Results were confirmed in a new experiment developed with young plants
      of cultivars 'Picual' (highly susceptible), 'Arbequina' (moderately susceptible)
      and 'Frantoio' (resistant), growing in pots under greenhouse conditions, either
      inoculated or not with V. dahliae. In this experiment, the pathogen DNA content,
      quantified by real-time PCR, and the density of occluded vessels, recorded by
      microscopic observations of transversal sections stained with toluidine blue,
      were related to the symptoms severity caused by the pathogen. Finally, a drought
      experiment was established with young plants of the cultivar 'Picual' grown in
      pots under greenhouse conditions in order to compare the effects caused by water
      deficit with those caused by the pathogen infection. In both cases, results show
      that starch hydrolysis occurred, what indirectly evidence the importance of xylem
      cavitation in the development of the symptoms caused by V. dahliae but in the
      water stressed plants no vessel occlusion was detected.

PMID- 29445389
TI  - Interspecific Divergence of Two Sinalliaria (Brassicaceae) Species in Eastern
      China.
AB  - How endemic species originated in eastern Asia has interested botanists for a
      long time. In this study, we combined experimental and computational modeling
      approaches to examine the morphological and genetic divergence and reproductive
      isolation of two tentative species of Sinalliaria (Brassicaceae) endemic to
      eastern China, S. limprichtiana and S. grandifolia. Most of the examined
      morphological characters (including hairs of leaf blades and stems, corolla
      length and width, and flower stalk length) were well-delineated between two
      species at the same ploidy level, and there was clear evidence of reproductive
      isolation between them (mainly due to post-pollination barriers) in the common
      garden environment. There were also strong and consistent divergences in the
      population genetic data. Coalescent simulations based on sequence variation of
      the nuclear genes suggest that interspecific divergence began during the
      Pleistocene when the climate oscillated in eastern Asia. Gene flow between two
      species appears to have been very limited and asymmetrical. Our results suggested
      that both species are well-differentiated and that the fast divergence between
      them might have been together shaped by both stochastic processes and habitat
      selection pressures.

PMID- 29445390
TI  - Approaches and Recent Developments for the Commercial Production of Semi
      synthetic Artemisinin.
AB  - The antimalarial drug artemisinin is a natural product produced by the plant
      Artemisia annua. Extracts of A. annua have been used in Chinese herbal medicine
      for over two millennia. Following the re-discovery of A. annua extract as an
      effective antimalarial, and the isolation and structural elucidation of
      artemisinin as the active agent, it was recommended as the first-line treatment
      for uncomplicated malaria in combination with another effective antimalarial drug
      (Artemisinin Combination Therapy) by the World Health Organization (WHO) in 2002.
      Following the WHO recommendation, the availability and price of artemisinin
      fluctuated greatly, ranging from supply shortfalls in some years to oversupply in
      others. To alleviate these supply and price issues, a second source of
      artemisinin was sought, resulting in an effort to produce artemisinic acid, a
      late-stage chemical precursor of artemisinin, by yeast fermentation, followed by
      chemical conversion to artemisinin (i.e., semi-synthesis). Engineering to enable
      production of artemisinic acid in yeast relied on the discovery of A. annua genes
      encoding artemisinic acid biosynthetic enzymes, and synthetic biology to engineer
      yeast metabolism. The progress of this effort, which resulted in semi-synthetic
      artemisinin entering commercial production in 2013, is reviewed with an emphasis
      on recent publications and opportunities for further development. Aspects of both
      the biology of artemisinin production in A. annua, and yeast strain engineering
      are discussed, as are recent developments in the chemical conversion of
      artemisinic acid to artemisinin.

PMID- 29445391
TI  - ZIP13: A Study of Drosophila Offers an Alternative Explanation for the
      Corresponding Human Disease.
AB  - The fruit fly Drosophila melanogaster has become an important model organism to
      investigate metal homeostasis and human diseases. Previously we identified dZIP13
      (CG7816), a member of the ZIP transporter family (SLC39A) and presumably a zinc
      importer, is in fact physiologically primarily responsible to move iron from the
      cytosol into the secretory compartments in the fly. This review will discuss the
      implication of this finding for the etiology of Spondylocheirodysplasia-Ehlers
      Danlos Syndrome (SCD-EDS), a human disease defective in ZIP13. We propose an
      entirely different model in that lack of iron in the secretory compartment may
      underlie SCD-EDS. Altogether three different working models are discussed,
      supported by relevant findings made in different studies, with uncertainties, and
      questions remained to be solved. We speculate that the distinct ZIP13 sequence
      features, different from those of all other ZIP family members, may confer it
      special transport properties.

PMID- 29445392
TI  - How many parathyroid glands can be identified during thyroidectomy?: Evidence
      based data for medical experts.
AB  - Background: The purpose of this study is to provide guidance for medical experts
      regarding malpractice claims on permanent hypoparathyroidism by analyzing the
      number of parathyroid glands (PGs) identified during thyroidectomy and the
      clinical outcome. Methods: Parathyroid findings were documented in a standardized
      protocol for 357 patients undergoing thyroidectomy and treated by a single
      specialized surgeon. The resected thyroid was routinely dissected for
      accidentally removed PGs with consecutive autotransplantation and the
      pathological report also described unintentionally resected PGs. Follow-up was
      performed for 6 months. Results: The mean number of identified PGs was 2.28. No
      PGs were found in 20 (5.6%), one in 56 (15.7%), two in 126 (35.3%), three in 114
      (31.9%), and four in 41 (11.5%) cases. One patient (0.28%) had manifest permanent
      hypoparathyroidism, while ten patients (2.8%) had latent permanent
      hypoparathyroidism (hypocalcemia and normoparathyroidism). The risk factors
      identified for postoperative hypoparathyroidism were an increasing number of
      visualized PGs, autotransplantation, central neck dissection, and PGs in the
      histopathological work-up. For permanent hypoparathyroidism, PGs in the histology
      examination and neck dissection were significant, but the number of identified
      PGs was not. Conclusion: Even an experienced surgeon is not always able to find
      all four PGs during thyroidectomy and occasionally identifies none. Rather than
      focusing on identifying a minimum number of PGs, it is more important not to miss
      them in risky positions. A documented awareness of PGs, i. e., knowledge of
      variable parathyroid positions and their saving, is a prerequisite for surgical
      quality and to protect surgeons from claims.

PMID- 29445393
TI  - Adenoma and Polyp Detection Rates in Colonoscopy according to Indication.
AB  - Background: Adenoma detection rate (ADR) is a validated quality measure for
      screening colonoscopy, but there are little data for other indications. The
      distribution of adenomas is not well described for these indications. Aim: To
      describe ADR and the adenoma distribution in the proximal and distal colon based
      on colonoscopy indication. Methods: Outpatient colonoscopies are subdivided by
      indication. PDR and ADR for the entire colon and for proximal and distal colon.
      Data were compared using generalized estimating equations to adjust for
      clustering amongst endoscopists while controlling for patient age and gender.
      Results: 3436 colonoscopies were reviewed (51.2%: men (n = 1759)). Indications
      are screening 49.2%, surveillance 29.3%, change in bowel habit 8.4%, bleeding
      5.8%, colitides 3.0%, pain 2.8%, and miscellaneous 1.5%. Overall ADR was 37%
      proximal ADR 28%, and distal ADR 17%. PDR and ADR were significantly higher in
      surveillance than in screening (PDR: 69% versus 51%; ADR: 50% versus 33%; p =
      0.0001). Adenomas were more often detected in the proximal than in the distal
      colon, for all indications. Conclusions: Prevalence of polyps and adenomas
      differs based on colonoscopy indication. Adenoma detection is highest in
      surveillance and more commonly detected in the proximal colon. For quality
      assurance, distinct ADR and PDR targets may need to be established for different
      colonoscopy indications.

PMID- 29445394
TI  - Polyethylene Glycol for Small Bowel Capsule Endoscopy.
AB  - Capsule endoscopy has been the first-line examination for small bowel diseases,
      yet its diagnostic yield is restricted by unsatisfactory bowel preparation. To
      evaluate the clinical effectiveness of different dosages of polyethylene glycol
      in patients undergoing capsule endoscopy, we performed a comprehensive meta
      analysis of all randomized controlled trials involving polyethylene glycol in
      preparation for capsule endoscopy. The methodological quality of the trials was
      evaluated using the Cochrane Risk of Bias assessment instrument. In this study,
      12 RCTs involving 2072 patients were included in this review. Our review
      indicated that 4 L and 2 L polyethylene (PEG) before capsule endoscopy (CE) and
      500 mL PEG after CE increase the small bowel image quality, whereas 1 L PEG did
      not improve the small bowel image quality. PEG accelerated the gastric emptying
      time. There was no significant difference between the PEG group and control group
      in small bowel transit time, completion rates, and diagnostic yield.

PMID- 29445395
TI  - Platelet Distribution Width Levels Can Be a Predictor in the Diagnosis of
      Persistent Organ Failure in Acute Pancreatitis.
AB  - Purpose: The change of serum platelet indices such as platelet distribution width
      (PDW) has been reported in a series of inflammatory reaction and clinical
      diseases. However, the relationship between PDW and the incidence of persistent
      organ failure (POF) in acute pancreatitis (AP) has not been elucidated so far.
      Materials and Methods: A total of 135 patients with AP admitted within 72 hours
      from symptom onset of AP at our center between December 2014 and January 2016
      were included in this retrospective study. Demographic parameters on admission,
      organ failure assessment, laboratory data, and in-hospital mortality were
      compared between patients with and without POF. Multivariable logistic regression
      analyses were utilized to evaluate the predictive value of serum PDW for POF.
      Results: 30 patients were diagnosed with POF. Compared to patients without POF,
      patients with POF showed a significantly higher value of serum PDW on admission
      (14.88 +/- 2.24 versus 17.60 +/- 1.96%, P < 0.001). After multivariable analysis,
      high PDW level remained a risk factor for POF (odds ratio 39.42, 95% CI: 8.64
      179.77; P < 0.001). A PDW value of 16.45% predicted POF with an area under the
      curve (AUC) of 0.870, a sensitivity with 0.867, and a specificity with 0.771,
      respectively. Conclusions: Our results indicate that serum PDW on admission could
      be a predictive factor in AP with POF and may serve as a potential prognostic
      factor.

PMID- 29445397
TI  - Corrigendum to "Inositol(s) from Bench to Bedside in Endocrinology and
      Gynecology".
AB  - [This corrects the article DOI: 10.1155/2017/8515703.].

PMID- 29445396
TI  - Higher Ratio of Abdominal Subcutaneous to Visceral Adipose Tissue Related with
      Preservation of Islet beta-Cell Function in Healthy Individuals.
AB  - Objective: To investigate the relationship between abdominal adipose tissue
      distribution, beta-cell function, and insulin sensitivity (IS) in a Chinese
      population. Methods: One hundred and eighty-eight healthy subjects (healthy
      group), 239 with normal glucose, and 1~4 abnormal metabolic traits (metabolic
      dysfunction group, MD group) and 125 with hyperglycemia (hyperglycemia group)
      were studied. HOMA-IR, HOMA-B, Matsuda index, early- (I0-30/G0-30) and late-phase
      (I30-120/G30-120) insulin responses and the corresponding disposition indexes
      (DI) were calculated. The area of abdominal subcutaneous adipose tissue (ASAT)
      and visceral adipose tissue (VAT) was measured and the ratio of ASAT to VAT (SVR)
      was calculated. Results: SVR was correlated positively with Matsuda index in
      healthy, MD, and hyperglycemia groups, and inversely with HOMA-IR. SVR positively
      related with both early- and late-phase DI in the healthy group only. In the
      healthy group, the hyperbolas of I0-30/G0-30 and I30-120/G30-120 versus Matsuda
      index in the highest quarter of SVR were significantly right shifted compared to
      those in the lowest (both P < 0.05). Conclusions: In healthy adults, higher SVR
      was a protective factor for beta-cell function and IS, while in those with
      glucometabolic abnormality, higher SVR contributed to a relative better IS,
      indicating SVR is possible to be an early predicator of type 2 diabetes
      development.

PMID- 29445398
TI  - A New Method for the Determination of Sucrose Concentration in a Pure and Impure
      System: Spectrophotometric Method.
AB  - Analytical chemistry is a set of procedures and techniques used to identify and
      quantify the composition of a sample of material. It is also focused on
      improvements in experimental design and the creation of new measurement tools.
      Analytical chemistry has broad applications to forensics, medicine, science, and
      engineering. The objective of this study is to develop a new method of sucrose
      dosage using a spectrophotometry method in a pure and impure system (presence of
      glucose and fructose). The work performed shows the reliability of this method. A
      model linking sucrose solution absorbance and mass percentage of glucose and
      fructose has been developed using experimental design. The results obtained show
      that all the investigated factors (sucrose concentration, mass percentage of
      glucose, and mass percentage of fructose) have a positive effect on the
      absorbance. The effect of the interaction between glucose and fructose on the
      absorbance is very significant.

PMID- 29445400
TI  - Effect of Curcuma xanthorrhiza Supplementation on Systemic Lupus Erythematosus
      Patients with Hypovitamin D Which Were Given Vitamin D3 towards Disease Activity
      (SLEDAI), IL-6, and TGF-beta1 Serum.
AB  - Background: Curcumin contained in Curcuma xanthorrhiza is an immunomodulator that
      has similar biological effect as vitamin D. Combination of curcumin and vitamin
      D3 is expected to work synergistically. Objective: To determine the effect of
      Curcuma xanthorrhiza supplementation on vitamin D3 administration to SLEDAI, IL
      6, and TGF-beta1 serum in SLE patients with hypovitamin D. Methods: This was a
      double-blind RCT conducted in Saiful Anwar Hospital, Malang, in January 2016
      March 2017. Subjects were SLE active (SLEDAI > 3) with levels of 25(OH)D3 <= 30
      ng/ml and divided into two groups: those receiving cholecalciferol 3 * 400 IU and
      placebo 3 * 1 tablets (group I) and those receiving 3 * 400 IU cholecalciferol
      and Curcuma xanthorrhiza 3 * 20 mg for 3 months (group II). SLEDAI, levels of
      vitamin D, IL-6, and TGF-beta1 in serum were evaluated before and after the
      treatment. Results: There were no significant differences in SLEDAI reduction,
      decreased serum levels of IL-6, and increased levels of TGF-beta1 serum among
      groups after the treatment. Decreased levels of serum IL-6 have a positive
      correlation with SLEDAI reduction. Conclusion. Curcuma xanthorrhiza
      supplementation on vitamin D3 had no effects on SLEDAI and serum levels of IL-6
      and TGF-beta1. This clinical trial is registered with NCT03155477.

PMID- 29445399
TI  - Nesprin-2 Interacts with Condensin Component SMC2.
AB  - The nuclear envelope proteins, Nesprins, have been primarily studied during
      interphase where they function in maintaining nuclear shape, size, and
      positioning. We analyze here the function of Nesprin-2 in chromatin interactions
      in interphase and dividing cells. We characterize a region in the rod domain of
      Nesprin-2 that is predicted as SMC domain (aa 1436-1766). We show that this
      domain can interact with itself. It furthermore has the capacity to bind to SMC2
      and SMC4, the core subunits of condensin. The interaction was observed during all
      phases of the cell cycle; it was particularly strong during S phase and persisted
      also during mitosis. Nesprin-2 knockdown did not affect condensin distribution;
      however we noticed significantly higher numbers of chromatin bridges in Nesprin-2
      knockdown cells in anaphase. Thus, Nesprin-2 may have an impact on chromosomes
      which might be due to its interaction with condensins or to indirect mechanisms
      provided by its interactions at the nuclear envelope.

PMID- 29445401
TI  - Predictors of Women's Satisfaction with Hospital-Based Intrapartum Care in Asmara
      Public Hospitals, Eritrea.
AB  - Background: Exploring patient satisfaction contributes to provide quality
      maternity care, but there is paucity of epidemiologic data in Eritrea.
      Objectives: To determine the predictors of women's satisfaction with intrapartum
      care in Asmara public maternity hospitals in Eritrea. Methods: A cross-sectional
      study among 771 mothers who gave birth in three public Hospitals. Chi-square
      tests were done to analyze the difference in proportion and logistic regression
      to assess the predictors of satisfaction with intrapartum care. Results: Overall,
      only 20.8% of the participants were satisfied with intrapartum service. The key
      predictors of satisfaction with intrapartum care were provision of clean bed and
      beddings (AOR = 18.87, 2.33-15.75), privacy during examinations (AOR = 10.22,
      4.86-21.48), using understandable language (AOR = 8.72, 3.57-21.27), showing how
      to summon for help (AOR = 8.16, 4.30-15.48), showing baby immediately after birth
      (AOR = 8.14, 2.87-23.07), control of the delivery room (AOR = 6.86, 2.65-17.75),
      receiving back massage (AOR = 6.43, 3.23-12.81), toilet access and cleanliness
      (AOR = 6.09, 3.25-11.42), availability of chairs for relatives (AOR = 5.96, 3.14
      11.30), allowing parents to stay during labour (AOR = 3.52, 1.299-9.56), and
      request for permission before any procedure (AOR = 2.39, 1.28-4.46). Conclusion:
      To increase satisfaction with intrapartum care, maternity service providers need
      to address the general maternity ward cleanliness, improve the quality of
      physical facilities, and sensitize health providers for better communication with
      clients. Policy makers need to adopt strategies that ensure more women
      involvement in decision making and consideration of privacy and reassurance needs
      during the whole delivery process.

PMID- 29445402
TI  - Allogenic Adipose Tissue-Derived Mesenchymal Stem Cells Ameliorate Acute Hepatic
      Injury in Dogs.
AB  - Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are an attractive source
      for cell-based therapy of some diseases, including acute and chronic liver
      failure, in not only human medicine but also veterinary medicine. However, in
      veterinary medicine, no studies have reported the effects of AT-MSCs on liver
      injury in dogs. The purpose of this study was to investigate the effects of
      allogenic AT-MSCs on acute liver injury by carbon tetrachloride in dogs and to
      compare the therapeutic effects of AT-MSCs transplanted via the peripheral vein
      (PV) or splenic vein (SV). After transplantation of AT-MSCs through the PV or SV,
      serum liver enzymes were decreased significantly, and SV injection was more
      effective compared with PV injection. By comparing the number of engrafted AT
      MSCs in the liver, SV injection was significantly more effective than PV
      injection. mRNA expression levels of proinflammatory cytokines, such as IL-1, IL
      6, IL-8, and IFNgamma, in the liver were decreased significantly, but those of
      anti-inflammatory cytokines, such as IL-4 and IL-10, HGF, and VEGFA, were
      significantly increased after the first AT-MSC injection. These findings suggest
      that allogenic AT-MSCs injected via the PV or SV ameliorate acute hepatic injury
      in dogs, and AT-MSCs injected via the SV provide more effective improvement.

PMID- 29445403
TI  - Reversal of Experimental Liver Damage after Transplantation of Stem-Derived Cells
      Detected by FTIR Spectroscopy.
AB  - The transplantation of autologous BM-MSCs holds great potential for treating end
      stage liver diseases. The aim of this study was to compare the efficiency of
      transplanted rBM-MSCs and rBM-MSC-derived differentiated stem cells (rBM-MSC
      DSCs) for suppression of dimethylnitrosamine-injured liver damage in rat model.
      Synchrotron radiation Fourier-transform infrared (SR-FTIR) microspectroscopy was
      applied to investigate changes in the macromolecular composition. Transplantation
      of rBM-MSC-DSCs into liver-injured rats restored their serum albumin level and
      significantly suppressed transaminase activity as well as the morphological
      manifestations of liver disease. The regenerative effects of rBM-MSC-DSCs were
      corroborated unequivocally by the phenotypic difference analysis between liver
      tissues revealed by infrared spectroscopy. Spectroscopic changes in the spectral
      region from 1190-970 cm-1 (bands with absorbance maxima at 1150 cm-1, 1081 cm-1,
      and 1026 cm-1) indicated decreased levels of carbohydrates, in rBM-MSC-DSC
      transplanted livers, compared with untreated and rBM-MSC--transplanted animals.
      Principal component analysis (PCA) of spectra acquired from liver tissue could
      readily discriminate rBM-MSC-DSC-transplanted animals from the untreated and rBM
      MSC-transplanted animals. We conclude that the transplantation of rBM-MSC-DSCs
      effectively treats liver disease in rats and SR-FTIR microspectroscopy provides
      important insights into the fundamental biochemical alterations induced by the
      stem-derived cell transplantation, including an objective "signature" of the
      regenerative effects of stem cell therapy upon liver injury.

PMID- 29445404
TI  - Dental-Derived Stem Cells and Their Secretome and Interactions with
      Bioscaffolds/Biomaterials in Regenerative Medicine: From the In Vitro Research to
      Translational Applications.

PMID- 29445405
TI  - High Sensitivity of Human Adipose Stem Cells to Differentiate into Myofibroblasts
      in the Presence of C. aspersa Egg Extract.
AB  - Introduction: Regeneration therapy using adipose-derived stem cells (ADSC) has
      been proposed in the treatment of skin aging. Myofibroblast plays a relevant role
      in the organization of the extracellular matrix of the damaged skin. A natural
      extract was derived from the eggs of the mollusk Cryptomphalus aspersa (e-CAF)
      that seems to play a role on skin repair. We have investigated the potential
      effects of e-CAF in the differentiation of ADSC. Materials and methods: ADSC were
      cultured in the absence or presence of e-CAF (50 and 200 MUg/mL) for 24 hours and
      7 days. Real-time cell assay, morphological, immunofluorescence, and RT-PCR
      techniques were used to evaluate the cell culture and expression of alphaSMA,
      collagen I, and tropoelastin. Results: e-CAF induced significant reduction in the
      rate of growth of ADSC from 24 hours to 7 days of culture. e-CAF also induced
      bigger sizes, higher levels of cytoplasmic refringence and complexity, and a more
      polyhedral morphological changes in the cultured ADSC. The protein and mRNA
      expression of alphaSMA was significantly increased in e-CAF-cultured ADSC.
      Conclusion: e-CAF promotes ADSC differentiation to myofibroblasts and should be
      considered as a potential agent for the prevention and treatment of skin aging.

PMID- 29445406
TI  - Detection and Molecular Characterization of Human Adenovirus Infections among
      Hospitalized Children with Acute Diarrhea in Shanghai, China, 2006-2011.
AB  - Background: Human adenovirus (HAdV) is considered a significant enteropathogen
      associated with sporadic diarrhea in children. However, limited data are
      available regarding the epidemiology of HAdV in hospitalized children with viral
      diarrhea in Shanghai. The aim of this study was to characterize the epidemiology
      of HAdVs and describe their association with acute diarrhea in hospitalized
      children. Methods: A total of 674 fecal samples were subjected to PCR or RT-PCR
      to detect RVA, HuCV, HAstV, and HAdV. Results: HAdV infections were detected in
      4.7% (32/674) of specimens, with detection rates of 13.4% (11/82), 4.6% (8/174),
      3.2% (4/124), 4.1% (3/74), 2.0% (2/100), and 3.3% (4/120) from 2006 to 2011,
      respectively. Comprehensive detection of the four viruses revealed the presence
      of a high percentage (90.6%) of coinfections among HAdV-positive samples, where
      HAdV+RVA was the most prevalent coinfection. Of the 32 HAdV-positive samples,
      50.0% (16/32) were classified as HAdV-41, and 18.8% (6/32) were classified as
      HAdV-3. Almost 94.0% of children infected with HAdV were less than 24 months of
      age. Conclusions: These results clearly indicated diversity across the HAdV
      genotypes detected in inpatient children with acute diarrhea in Shanghai and
      suggested that HAdVs play a role in children with acute diarrhea.

PMID- 29445407
TI  - Practical outpatient pharmacotherapy for alcohol use disorder.
AB  - Alcohol use disorder (AUD) is commonly encountered in clinical practice. A
      combination of psychosocial intervention and pharmacotherapy is the cornerstone
      of AUD treatment. Despite their efficacy, safety and cost-effectiveness,
      clinicians are reluctant to prescribe medications to treat individuals with AUD.
      Given the high rate of relapse with psychosocial intervention alone, increasing
      patient access to this underutilized treatment has the potential to improve
      clinical outcome in this difficult-to-treat population. Herein, we provide
      practical pharmacotherapy strategies to improve treatment outcome for AUD. We
      review the efficacy and side effects of both on- and off-label agents with a
      particular focus on clinical applicability. Recommendations are supported by
      findings from randomized controlled trials (RCT) and meta-analyses selected to be
      representative, where possible, of current treatment guidelines. The goal of this
      paper is to help readers use pharmacotherapy with greater confidence when
      treating patients with AUD.

PMID- 29445408
TI  - Needs and preferences of women users of oral contraceptives in selected countries
      in Central and Eastern Europe.
AB  - Background: The availability of various oral contraceptive (OC) pill formulations
      with different hormone compositions suggests that there is potential to align a
      particular product with an individual user's needs and preferences. To explore
      this concept further, a survey was conducted of current users of OCs to define
      and confirm areas of specific needs, and to gain insight into their views and
      preferences for OC formulations. Methods: During November and December 2015,
      women users (n=615) of OCs in five Central and Eastern European countries were
      surveyed in face-to-face interviews conducted by experienced interviewers. The
      survey questionnaire comprised 34 questions about the use of and specific needs
      for OCs. Results: Four basic needs of women taking OCs were identified: reliable
      contraception, reversibility of contraception, no effect on body weight and
      safety. Overall, 85% of surveyed women indicated that prevention of pregnancy was
      the main reason for taking OCs. Weight gain was the side effect of greatest
      concern with OC use (46% spontaneous answer; 65% aided answer). Independent
      behavioural segmentation analysis identified four groups - Solved Cycle Problems
      (46% of participants), Low Hormone Content (22%), Lifestyle (17%) and Beauty
      (14%) - which characterised the women according to needs and preferences beyond
      the basic needs of OCs. Each group had unique features and distinct preferences
      for different formulations of OCs. Conclusions: Aligning product advantages with
      specific individual needs may enhance users' overall experience with OCs as a
      contraceptive option.

PMID- 29445409
TI  - Suvorexant for insomnia in older adults: a perspective review.
AB  - The aim of this review was to identify published randomized control trials (RCTs)
      that evaluated the efficacy and tolerability of suvorexant for the treatment of
      insomnia among older adults (>=65 years). A literature search was conducted of
      PubMed, MEDLINE, EMBASE, PsycINFO and Cochrane collaboration databases for RCTs
      in any language evaluating suvorexant for the treatment of insomnia in older
      adults. Additionally, references of full-text articles that were included in this
      review were searched for further studies. Data from three RCTs of suvorexant were
      included in this review. All the three studies fulfilled the criteria for being
      of good quality based on the items listed by the Center for Evidence Based
      Medicine (CEBM) for the assessment of RCTs. None of the three studies were
      conducted exclusively among older adults. However, they also included older
      individuals diagnosed with primary insomnia. These studies included a total of
      1298 participants aged >=65 years in age. Trial durations ranged from 3 months to
      1 year. Available data from these studies indicate that suvorexant improves
      multiple subjective and polysomnographic sleep parameters for sleep onset and
      maintenance among older individuals with a diagnosis of primary insomnia and is
      generally well tolerated. Current evidence, although limited, indicates that
      suvorexant benefits older adults with primary insomnia and is generally well
      tolerated.

PMID- 29445410
TI  - Enrichment of Phenolic Compounds from Olive Mill Wastewater and In Vitro
      Evaluation of Their Antimicrobial Activities.
AB  - The production of olive oil generates massive quantities of by-product called
      olive mill wastewater (OMWW). The uncontrolled disposal of OMWW poses serious
      environmental problems. The OMWW effluent is rich in several polyphenolic
      compounds. Liquid-liquid extraction of OMWW using ethyl acetate solvent was used
      to enrich phenolic compounds under investigation. Total phenolic and flavonoid
      content and antioxidant activity of the extract were determined. HPLC coupled to
      photodiode array (PDA) detector was used to analyze the main three phenolic
      compounds of OMWW, namely, hydroxytyrosol, tyrosol, and oleuropein. The
      antimicrobial activity of the extract was also investigated. Additionally, the
      OMWW extract was used as natural preservative and antioxidants for olive oil.
      Results showed that OMWW is very rich in phenolic compounds and has strong
      antioxidant activity. HPLC analysis showed that the extract contains mainly
      hydroxytyrosol and tyrosol but no oleuropein. The OMWW extract showed also
      positive activities as antibacterial (gram positive and gram negative) and
      antifungal as well as activities against yeast. The addition of OMWW extract to
      olive oil samples has an effect on the stability of olive oil as reflected by its
      acid value, peroxide value, K232 and K270, and total phenolic content.

PMID- 29445411
TI  - Memory Improvement Effect of Ethanol Garlic (A. sativum) Extract in
      Streptozotocin-Nicotinamide Induced Diabetic Wistar Rats Is Mediated through
      Increasing of Hippocampal Sodium-Potassium ATPase, Glutamine Synthetase, and
      Calcium ATPase Activities.
AB  - Studies suggest that garlic (A. sativum) improves memory dependent on the
      hippocampus. However, the effect of ethanol garlic extract on hippocampus Na+/K+
      ATPase, Ca2+ ATPase, and glutamine synthetase (GS) activities as possible
      mechanisms in memory improvement in diabetic Wistar rats has not been reported.
      Twenty-four male Wistar rats weighing 200-250 g were divided into three groups
      with 8 rats each. Group (A), normal control rats, and Group (B), diabetic rats,
      received 1 ml of normal saline; diabetic rats in Group (C) received 1000 mg/kg of
      garlic extract orally for 21 days. Hyperglycemia was induced by a single
      intraperitoneal injection of streptozotocin 60 mg/kg followed by 120 mg/kg
      nicotinamide while extraction of garlic was done by cold maceration method.
      Memory was tested in all groups. After that, the rats were sacrificed, the brain
      was removed, and the hippocampi were carefully excised and then homogenized.
      Activities of Na+/K+ ATPase, calcium ATPase, and GS were analyzed from the
      homogenate. Results showed improvement in memory and a significant increase (P <
      0.05) in hippocampus Na+/K+ ATPase, Ca2+ ATPase, and GS activities in diabetic
      rats treated with garlic extract. In conclusion, the increased activity of
      hippocampus Na+/K+ ATPase, calcium ATPase, and glutamine synthetase may account
      for the memory improvement.

PMID- 29445412
TI  - Aqueous Extracts of Herba Cistanche Promoted Intestinal Motility in Loperamide
      Induced Constipation Rats by Ameliorating the Interstitial Cells of Cajal.
AB  - Traditional Chinese medicine was reported to have good effects in treating
      functional constipation. This work attempted to prove the effects of aqueous
      extracts of Herba Cistanche (AEHC) on STC treatment and to determine the possible
      mechanisms by a loperamide-induced slow transit constipation (STC) model. HPLC
      was performed for identification and confirmation of the bioactive components in
      the AEHC. It was found that AEHC attenuated STC responses based on increased
      fecal quantity, moisture content, and intestinal transit rate, as well as serum
      levels of GAS, MTL, SS, and CGRP. The protein and mRNA levels of c-kit, a
      labeling of interstitial cells of Cajal (ICC), also increased. Meanwhile, only
      the protein level of SCF, a ligand of c-kit, increased. The analysis of our data
      suggested that AEHC could obviously improve the function of ICC via a signaling
      pathway involving PI3K, SCF, and c-kit and enhance colonic motility indices such
      as GAS, MTL, SS, and CGRP. It is interesting to note that AEHC appeared to be
      effective on constipation, so further experiments are necessary to clarify the
      exact mechanisms involved.

PMID- 29445413
TI  - Icariin Regulates the Bidirectional Differentiation of Bone Marrow Mesenchymal
      Stem Cells through Canonical Wnt Signaling Pathway.
AB  - Fat infiltration within the bone marrow is easily observed in some postmenopausal
      women. Those fats are mainly derived from bone marrow mesenchymal stem cells
      (BMMSCs). The increment of adipocytes derived from BMMSCs leads to decreased
      osteoblasts derived from BMMSCs, so the bidirectional differentiation of BMMSCs
      significantly contributes to osteoporosis. Icariin is the main extractive of
      Herba Epimedii which is widely used in traditional Chinese medicine. In this
      experiment, we investigated the effect of icariin on the bidirectional
      differentiation of BMMSCs through quantitative real-time PCR, immunofluorescence,
      western blot, and tissue sections in vitro and in vivo. We found that icariin
      obviously promotes osteogenesis and inhibits adipogenesis through detecting
      staining and gene expression. Micro-CT analysis showed that icariin treatment
      alleviated the loss of cancellous bone of the distal femur in ovariectomized
      (OVX) mice. H&E staining analysis showed that icariin-treated OVX mice obtained
      higher bone mass and fewer bone marrow lipid droplets than OVX mice. Western blot
      and immunofluorescence showed that icariin regulates the bidirectional
      differentiation of BMMSCs via canonical Wnt signaling. This study demonstrates
      that icariin exerts its antiosteoporotic effect by regulating the bidirectional
      differentiation of BMMSCs through the canonical Wnt signaling pathway.

PMID- 29445414
TI  - Effects of a new nutraceutical combination on cognitive function in hypertensive
      patients.
AB  - Background: Chronic increased arterial blood pressure has been associated with
      executive dysfunction, slowing of attention and mental processing speed, and
      later with memory deficits. Due to the absence of a concrete therapeutic approach
      to this pathophysiological process, in the last decades there has been an
      increasing interest in the use of nutraceuticals, especially those with
      antioxidant properties, which own strong neuroprotective potential, that may help
      to improve cognitive function and to delay the onset of dementia. Results: We
      evaluated the effects of the treatment with a new nutraceutical preparation
      containing different molecules with potent antioxidant properties (AkP05,
      IzzeK(r)) and placebo on a cohort of thirty-six hypertensive patients. At
      baseline, neuropsychological evaluation, arterial stiffness and biochemical
      parameters of the subjects were comparable. After 6 months of treatment, there
      was a significant reduction of the augmentation index in the AkP05-treated group.
      Moreover, the measurement of cognitive function, evaluated with MoCA test and
      Word Match Testing, showed a significant improvement in patients receiving the
      active treatment. In addition, the group treated with nutraceutical reached a
      better Stroop test score, while subjects that received placebo did not showed any
      improvement. Finally, a positive relationship between SBP variation and the
      psychometric assessment with the EQ-VAS scale was observed only in the active
      treatment group. Conclusions: In this study, we demonstrated that the therapy
      with a new nutraceutical preparation is able to significantly increase the scores
      of important neuropsychological tests in hypertensive patients already on
      satisfactory blood pressure control. Although future studies are needed to better
      characterize the molecular mechanisms involved, these results candidate the new
      nutraceutical combination as a possible therapeutic strategy to support the
      cerebrovascular functions and delay the onset of dementia in hypertensive
      patients.

PMID- 29445415
TI  - Curcumin and piperine supplementation of obese mice under caloric restriction
      modulates body fat and interleukin-1beta.
AB  - Background: Dietary bioactive compounds capable of improving metabolic profiles
      would be of great value, especially for overweight individuals undergoing a
      caloric restriction (CR) regimen. Curcumin (Cur), a possible anti-obesity
      compound, and piperine (Pip), a plausible enhancer of Cur's bioavailability and
      efficacy, may be candidate agents for controlling body fat, metabolism and low
      grade inflammation. Methods: 47 eight-week-old male C57BL/6 mice were fed a high
      fat diet (HFD) for 23 weeks to induce obesity. Then, mice were divided into 5
      groups. Group 1 continued on HFD ad libitum. The other 4 groups underwent CR
      (reduced 10% HFD intake for 10 weeks, 20% for 20 weeks) with Cur, Pip, Cur + Pip
      or none of these. Percent body fat, plasma inflammatory markers associated with
      obesity (interferon (IFN)-gamma, interleukin (IL)-10, IL-12 p70, IL-1beta, IL-6
      and KC/GRO), plasma Cur metabolites and liver telomere length were measured.
      Results: Compared to the other groups, obese mice who underwent CR and received
      Cur + Pip in their diet lost more fat and had significantly lower IL-1beta and
      KC/GRO. Tandem mass spectrometry analysis of plasma from obese mice under CR
      showed no difference in Cur metabolite levels between groups supplemented with
      Cur alone or combined with Pip. However, plasma IL-1beta levels were inversely
      correlated with curcumin glucuronide. Minor modulation of telomere length were
      observed. Conclusions: It is plausible that supplementing the high fat diet of CR
      mice with Cur + Pip may increase loss of body fat and suppresses HFD induced
      inflammation. Combination of Cur and Pip has potential to enhance CR effects for
      the prevention of metabolic syndrome.

PMID- 29445416
TI  - A safe and complete algorithm for metagenomic assembly.
AB  - Background: Reconstructing the genome of a species from short fragments is one of
      the oldest bioinformatics problems. Metagenomic assembly is a variant of the
      problem asking to reconstruct the circular genomes of all bacterial species
      present in a sequencing sample. This problem can be naturally formulated as
      finding a collection of circular walks of a directed graph G that together cover
      all nodes, or edges, of G. Approach: We address this problem with the "safe and
      complete" framework of Tomescu and Medvedev (Research in computational Molecular
      biology-20th annual conference, RECOMB 9649:152-163, 2016). An algorithm is
      called safe if it returns only those walks (also called safe) that appear as
      subwalk in all metagenomic assembly solutions for G. A safe algorithm is called
      complete if it returns all safe walks of G. Results: We give graph-theoretic
      characterizations of the safe walks of G, and a safe and complete algorithm
      finding all safe walks of G. In the node-covering case, our algorithm runs in
      time [Formula: see text], and in the edge-covering case it runs in time [Formula:
      see text]; n and m denote the number of nodes and edges, respectively, of G. This
      algorithm constitutes the first theoretical tight upper bound on what can be
      safely assembled from metagenomic reads using this problem formulation.

PMID- 29445418
TI  - Local constructions of gender-based violence amongst IDPs in northern Uganda:
      analysis of archival data collected using a gender- and age-segmented
      participatory ranking methodology.
AB  - Background: Gender-based violence (GBV) is a significant problem in conflict
      affected settings. Understanding local constructions of such violence is crucial
      to developing preventive and responsive interventions to address this issue.
      Methods: This study reports on a secondary analysis of archived data collected as
      part of formative qualitative work - using a group participatory ranking
      methodology (PRM) - informing research on the prevalence of GBV amongst IDPs in
      northern Uganda in 2006. Sixty-four PRM group discussions were held with women,
      with men, with girls (aged 14 to 18 years), and with boys (aged 14 to 18 years)
      selected on a randomized basis across four internally displaced persons (IDP)
      camps in Lira District. Discussions elicited problems facing women in the camps,
      and - through structured participatory methods - consensus ranking of their
      importance and narrative accounts explaining these judgments. Results: Amongst
      forms of GBV faced by women, rape was ranked as the greatest concern amongst
      participants (with a mean problem rank of 3.4), followed by marital rape (mean
      problem rank of 4.5) and intimate partner violence (mean problem rank of 4.9).
      Girls ranked all forms of GBV as higher priority concerns than other
      participants. Discussions indicated that these forms of GBV were generally
      considered normalized within the camp. Gender roles and power, economic
      deprivation, and physical and social characteristics of the camp setting emerged
      as key explanatory factors in accounts of GBV prevalence, although these played
      out in different ways with respect to differing forms of violence. Conclusions:
      All groups acknowledged GBV to represent a significant threat - among other major
      concerns such as transportation, water, shelter, food and security - for women
      residing in the camps. Given evidence of the significantly higher risk in the
      camp of intimate partner violence and marital rape, the relative prominence of
      the issue of rape in all rankings suggests normalization of violence within the
      home. Programs targeting reduction in GBV need to address community-identified
      root causes such as economic deprivation and social norms related to gender
      roles. More generally, PRM appears to offer an efficient means of identifying
      local constructions of prevailing challenges in a manner that can inform
      programming.

PMID- 29445417
TI  - Bioactive polysaccharides from natural resources including Chinese medicinal
      herbs on tissue repair.
AB  - Background: Functional polysaccharides can be derived from plants (including
      herbs), animals and microorganisms. They have been widely used in a broad of
      biomedical applications, such as immunoregulatory agents or drug delivery
      vehicles. In the past few years, increasing studies have started to develop
      natural polysaccharides-based biomaterials for various applications in tissue
      engineering and regenerative medicine. Main body: We discuss in this article the
      emerging applications of natural polysaccharides-particularly those derived from
      Chinese medicine-for wound healing. First, we introduce natural polysaccharides
      of three natural sources and their biological activities. Then, we focus on
      certain natural polysaccharides with growth factor-binding affinities and their
      inspired polymeric tools, with an emphasis on how these polysaccharides could
      possibly benefit wound healing. Finally, we report the latest progress in the
      discovery of polysaccharides from Chinese medicinal herbs with identified
      activities favouring tissue repair. Conclusion: Natural polysaccharides with
      clearly elucidated compositions/structures, identified cellular activities, as
      well as desirable physical properties have shown the potential to serve as
      therapeutic tools for tissue regeneration.

PMID- 29445419
TI  - Highly efficient conversion of plant oil to bio-aviation fuel and valuable
      chemicals by combination of enzymatic transesterification, olefin cross
      metathesis, and hydrotreating.
AB  - Background: The production of fuels and chemicals from renewable resources is
      increasingly important due to the environmental concern and depletion of fossil
      fuel. Despite the fast technical development in the production of aviation fuels,
      there are still several shortcomings such as a high cost of raw materials, a low
      yield of aviation fuels, and poor process techno-economic consideration. In
      recent years, olefin metathesis has become a powerful and versatile tool for
      generating new carbon-carbon bonds. The cross-metathesis reaction, one kind of
      metathesis reaction, has a high potential to efficiently convert plant oil into
      valuable chemicals, such as alpha-olefin and bio-aviation fuel by combining with
      a hydrotreatment process. Results: In this research, an efficient, four-step
      conversion of plant oil into bio-aviation fuel and valuable chemicals was
      developed by the combination of enzymatic transesterification, olefin cross
      metathesis, and hydrotreating. Firstly, plant oil including oil with poor
      properties was esterified to fatty acid methyl esters by an enzyme-catalyzed
      process. Secondly, the fatty acid methyl esters were partially hydrotreated
      catalytically to transform poly-unsaturated fatty acid such as linoleic acid into
      oleic acid. The olefin cross-metathesis then transformed the oleic acid methyl
      ester (OAME) into 1-decene and 1-decenoic acid methyl ester (DAME). The catalysts
      used in this process were prepared/selected in function of the catalytic reaction
      and the reaction conditions were optimized. The carbon efficiency analysis of the
      new process illustrated that it was more economically feasible than the
      traditional hydrotreatment process. Conclusions: A highly efficient conversion
      process of plant oil into bio-aviation fuel and valuable chemicals by the
      combination of enzymatic transesterification, olefin cross-metathesis, and
      hydrotreatment with prepared and selected catalysts was designed. The reaction
      conditions were optimized. Plant oil was transformed into bio-aviation fuel and a
      high value alpha-olefin product with high carbon utilization.

PMID- 29445420
TI  - A bionic system with Fenton reaction and bacteria as a model for bioprocessing
      lignocellulosic biomass.
AB  - Background: The recalcitrance of lignocellulosic biomass offers a series of
      challenges for biochemical processing into biofuels and bio-products. For the
      first time, we address these challenges with a biomimetic system via a mild yet
      rapid Fenton reaction and lignocellulose-degrading bacterial strain Cupriavidus
      basilensis B-8 (here after B-8) to pretreat the rice straw (RS) by mimicking the
      natural fungal invasion process. Here, we also elaborated the mechanism through
      conducting a systematic study of physicochemical changes before and after
      pretreatment. Results: After synergistic Fenton and B-8 pretreatment, the
      reducing sugar yield was increased by 15.6-56.6% over Fenton pretreatment alone
      and 2.7-5.2 times over untreated RS (98 mg g-1). Morphological analysis revealed
      that pretreatment changed the surface morphology of the RS, and the increase in
      roughness and hydrophilic sites enhanced lignocellulose bioavailability. Chemical
      components analyses showed that B-8 removed part of the lignin and hemicellulose
      which caused the cellulose content to increase. In addition, the important
      chemical modifications also occurred in lignin, 2D NMR analysis of the lignin in
      residues indicated that the Fenton pretreatment caused partial depolymerization
      of lignin mainly by cleaving the beta-O-4 linkages and by demethoxylation to
      remove the syringyl (S) and guaiacyl (G) units. B-8 could depolymerize amount of
      the G units by cleaving the beta-5 linkages that interconnect the lignin
      subunits. Conclusions: A biomimetic system with a biochemical Fenton reaction and
      lignocellulose-degrading bacteria was confirmed to be able for the pretreatment
      of RS to enhance enzymatic hydrolysis under mild conditions. The high
      digestibility was attributed to the destruction of the lignin structure, partial
      hydrolysis of the hemicellulose and partial surface oxidation of the cellulose.
      The mechanism of synergistic Fenton and B-8 pretreatment was also explored to
      understand the change in the RS and the bacterial effects on enzymatic
      hydrolysis. Furthermore, this biomimetic system offers new insights into the
      pretreatment of lignocellulosic biomass.

PMID- 29445421
TI  - Evidence for a pre-malignant cell line in a skin biopsy from a patient with
      Nijmegen breakage syndrome.
AB  - Background: Nijmegen breakage syndrome is an autosomal recessive disorder
      characterized by microcephaly, immunodeficiency, hypersensitivity to X
      irradiation, and a high predisposition to cancer. Nibrin, the product of the NBN
      gene, is part of the MRE11/RAD50 (MRN) complex that is involved in the repair of
      DNA double strand breaks (DSBs), and plays a critical role in the processing of
      DSBs in immune gene rearrangements, telomere maintenance, and meiotic
      recombination. NBS skin fibroblasts grow slowly in culture and enter early into
      senescence. Case presentation: Here we present an incidental finding. Skin
      fibroblasts, derived from a 9 year old NBS patient, showed a mosaic of normal
      diploid cells (46,XY) and those with a complex, unbalanced translocation. The
      aberrant karyotype was analysed by G-banding, comparative genomic hybridization,
      and whole chromosome painting. The exact breakpoints of the derivative chromosome
      were mapped by whole genome sequencing: 45,XY,der(6)(6pter -> 6q11.1::13q11 ->
      13q21.33::20q11.22 -> 20qter),-13. The deleted region of chromosomes 6 harbors
      almost 1.400 and that of chromosome 13 more than 500 genes, the duplicated region
      of chromosome 20 contains about 700 genes. Such unbalanced translocations are
      regularly incompatible with cellular survival, except in malignant cells. The
      aberrant cells, however, showed a high proliferation potential and could even be
      clonally expanded. Telomere length was significantly reduced, hTERT was not
      expressed. The cells underwent about 50 population doublings until they entered
      into senescence. The chromosomal preparation performed shortly before senescence
      showed telomere fusions, premature centromere divisions, endoreduplications and
      tetraploid cells, isochromatid breaks and a variety of marker chromosomes.
      Inspection of the site of skin biopsy 18 years later, presented no evidence for
      abnormal growth. Conclusions: The aberrant cells had a significant selective
      advantage in vitro. It is therefore tempting to speculate that this highly
      unbalanced translocation could be a primary driver of cancer cell growth.

PMID- 29445422
TI  - Sleeping Beauty transposon integrates into non-TA dinucleotides.
AB  - Background: Sleeping Beauty transposon (SB) has become an increasingly important
      genetic tool for generating mutations in vertebrate cells. It is widely thought
      that SB exclusively integrates into TA dinucleotides. However, this strict TA
      preference has not been rigorously tested in large numbers of insertion sites
      that now can be detected with next generation sequencing. Li et al. found 71 SB
      insertions in non-TA dinucleotides in 2013, suggesting that TA dinucleotides are
      not the only sites of SB integration, yet further studies on this topic have not
      been carried out. Results: In this study, we re-analyzed 600 million pairs of
      Illumina sequence reads from a high-throughput SB mutagenesis screen and
      identified 28 thousand SB insertions in non-TA sites. We recovered some of these
      non-TA sites using PCR and confirmed that at least a subset of the insertions at
      non-TA sites are real integrations. The consensus sequence of these non-TA sites
      shows an asymmetric pattern distinct from the symmetric pattern of the canonical
      TA sites. Perfect similarity between the downstream flanking sequence and SB
      transposon ends indicates there may be interaction between the transposon DNA
      binding domain of transposase and the target DNA. Conclusion: The TA-preference
      of SB transposon is not as strict as what people had thought. And the SB
      integrations at non-TA sites might be guided by the interaction between the
      transposon DNA binding domain of SB transposase and the target DNA.

PMID- 29445423
TI  - An update on vitamin B12-related gene polymorphisms and B12 status.
AB  - Background: Vitamin B12 is an essential micronutrient in humans needed for health
      maintenance. Deficiency of vitamin B12 has been linked to dietary, environmental
      and genetic factors. Evidence for the genetic basis of vitamin B12 status is
      poorly understood. However, advancements in genomic techniques have increased the
      knowledge-base of the genetics of vitamin B12 status. Based on the candidate gene
      and genome-wide association (GWA) studies, associations between genetic loci in
      several genes involved in vitamin B12 metabolism have been identified. Objective:
      The objective of this literature review was to identify and discuss reports of
      associations between single-nucleotide polymorphisms (SNPs) in vitamin B12
      pathway genes and their influence on the circulating levels of vitamin B12.
      Methods: Relevant articles were obtained through a literature search on PubMed
      through to May 2017. An article was included if it examined an association of a
      SNP with serum or plasma vitamin B12 concentration. Beta coefficients and odds
      ratios were used to describe the strength of an association, and a P < 0.05 was
      considered as statistically significant. Two reviewers independently evaluated
      the eligibility for the inclusion criteria and extracted the data. Results: From
      23 studies which fulfilled the selection criteria, 16 studies identified SNPs
      that showed statistically significant associations with vitamin B12
      concentrations. Fifty-nine vitamin B12-related gene polymorphisms associated with
      vitamin B12 status were identified in total, from the following populations:
      African American, Brazilian, Canadian, Chinese, Danish, English, European
      ancestry, Icelandic, Indian, Italian, Latino, Northern Irish, Portuguese and
      residents of the USA. Conclusion: Overall, the data analyzed suggests that ethnic
      specific associations are involved in the genetic determination of vitamin B12
      concentrations. However, despite recent success in genetic studies, the majority
      of identified genes that could explain variation in vitamin B12 concentrations
      were from Caucasian populations. Further research utilizing larger sample sizes
      of non-Caucasian populations is necessary in order to better understand these
      ethnic-specific associations.

PMID- 29445425
TI  - Mosaicism for GNAS methylation defects associated with pseudohypoparathyroidism
      type 1B arose in early post-zygotic phases.
AB  - Background: Pseudohypoparathyroidism type 1B (PHP1B; MIM#603233) is a rare
      imprinting disorder (ID), associated with the GNAS locus, characterized by
      parathyroid hormone (PTH) resistance in the absence of other endocrine or
      physical abnormalities. Sporadic PHP1B cases, with no known underlying primary
      genetic lesions, could represent true stochastic errors in early embryonic
      maintenance of methylation. Previous data confirmed the existence of different
      degrees of methylation defects associated with PHP1B and suggested the presence
      of mosaicism, a phenomenon already described in the context of other IDs.
      Results: With respect to mosaic conditions, the study of multiple tissues is a
      necessary approach; thus, we investigated somatic cell lines (peripheral blood
      and buccal epithelium and cells from the urine sediment) descending from
      different germ layers from 19 PHP patients (11 spor-PHP1B, 4 GNAS mutated PHP1A,
      and 4 PHP with no GNAS (epi)genetic defects) and 5 healthy controls. We
      identified 11 patients with epigenetic defects, further subdivided in groups with
      complete or partial methylation defects. The recurrence of specific patterns of
      partial methylation defects limited to specific CpGs was confirmed by checking
      methylation profiles of spor-PHP1B patients diagnosed in our lab (n = 56).
      Underlying primary genetic defects, such as uniparental disomy or deletion,
      potentially causative for the detected partial methylation were excluded in all
      samples. Conclusions: Our data showed no differences of methylation levels
      between organs and tissues from the same patient, so we concluded that the
      epimutation occurred in early post-zygotic phases and that the partial defects
      were mosaics. The number of patients with no detectable (epi)genetic GNAS defects
      was too small to exclude epimutations occurring in later post-zygotic phases,
      affecting only selected tissues different from blood, thus leading to
      underdiagnosis during routine molecular diagnosis. Finally, we found no
      correlation between methylation ratios, representing the proportion of epimutated
      cells, and the clinical presentation, further confirming the hypothesis of a
      threshold effect of the GNAS loss of imprinting leading to an "all-or-none"
      phenotype.

PMID- 29445424
TI  - Promoter methylation of DNA damage repair (DDR) genes in human tumor entities:
      RBBP8/CtIP is almost exclusively methylated in bladder cancer.
AB  - Background: Genome-wide studies identified pan-cancer genes and shared biological
      networks affected by epigenetic dysregulation among diverse tumor entities. Here,
      we systematically screened for hypermethylation of DNA damage repair (DDR) genes
      in a comprehensive candidate-approach and exemplarily identify and validate
      candidate DDR genes as targets of epigenetic inactivation unique to bladder
      cancer (BLCA), which may serve as non-invasive biomarkers. Methods: Genome-wide
      DNA methylation datasets (2755 CpG probes of n = 7819 tumor and n = 659 normal
      samples) of the TCGA network covering 32 tumor entities were analyzed in silico
      for 177 DDR genes. Genes of interest were defined as differentially methylated
      between normal and cancerous tissues proximal to transcription start sites. The
      lead candidate gene was validated by methylation-specific PCR (MSP) and/or
      bisulfite-pyrosequencing in different human cell lines (n = 36), in primary BLCA
      tissues (n = 43), and in voided urine samples (n = 74) of BLCA patients. Urines
      from healthy donors and patients with urological benign and malignant diseases
      were included as controls (n = 78). mRNA expression was determined using qRT-PCR
      in vitro before (n = 5) and after decitabine treatment (n = 2). Protein
      expression was assessed by immunohistochemistry (n = 42). R 3.2.0. was used for
      statistical data acquisition and SPSS 21.0 for statistical analysis. Results:
      Overall, 39 DDR genes were hypermethylated in human cancers. Most exclusively and
      frequently methylated (37%) in primary BLCA was RBBP8, encoding endonuclease
      CtIP. RBBP8 hypermethylation predicted longer overall survival (OS) and was found
      in 2/4 bladder cancer cell lines but not in any of 33 cancer cell lines from
      entities with another origin like prostate. RBBP8 methylation was inversely
      correlated with RBBP8 mRNA and nuclear protein expression while RBBP8 was re
      expressed after in vitro demethylation. RBBP8 methylation was associated with
      histological grade in primary BLCA and urine samples. RBBP8 methylation was
      detectable in urine samples of bladder cancer patients achieving a sensitivity of
      52%, at 91% specificity. Conclusions: RBBP8 was identified as almost exclusively
      hypermethylated in BLCA. RBBP8/CtIP has a proven role in homologous recombination
      mediated DNA double-strand break repair known to sensitize cancer cells for PARP1
      inhibitors. Since RBBP8 methylation was detectable in urines, it may be a
      complementary marker of high specificity in urine for BLCA detection.

PMID- 29445426
TI  - The effect of different methods and image analyzers on the results of the in vivo
      comet assay.
AB  - Introduction: The in vivo comet assay is a widely used genotoxicity test that can
      detect DNA damage in a range of organs. It is included in the Organisation for
      Economic Co-operation and Development Guidelines for the Testing of Chemicals.
      However, various protocols are still used for this assay, and several different
      image analyzers are used routinely to evaluate the results. Here, we verified a
      protocol that largely contributes to the equivalence of results, and we assessed
      the effect on the results when slides made from the same sample were analyzed
      using two different image analyzers (Comet Assay IV vs Comet Analyzer). Findings:
      Standardizing the agarose concentrations and DNA unwinding and electrophoresis
      times had a large impact on the equivalence of the results between the different
      methods used for the in vivo comet assay. In addition, there was some variation
      in the sensitivity of the two different image analyzers tested; however this
      variation was considered to be minor and became negligible when the test
      conditions were standardized between the two different methods. Conclusion: By
      standardizing the concentrations of low melting agarose and DNA unwinding and
      electrophoresis times between both methods used in the current study, the
      sensitivity to detect the genotoxicity of a positive control substance in the in
      vivo comet assay became generally comparable, independently of the image analyzer
      used. However, there may still be the possibility that other conditions, except
      for the three described here, could affect the reproducibility of the in vivo
      comet assay.

PMID- 29445427
TI  - A Novel Open-Framework Cu-Ge-Based Chalcogenide Anode Material for Sodium-Ion
      Battery.
AB  - Open-framework chalcogenides are potential electrode materials for sodium-ion
      batteries (SIBs) due to their architectures with fast-ion conductivity. Herein,
      we report on the successful synthesis of open-framework Cu-Ge-based chalcogenides
      [Cu8Ge6Se19](C5H12N)6 (CGSe) and the research of their energy storage application
      as SIB anodes for the first time. As a result, the CGSe anode exhibited good
      electrochemical performances such as high reversible capacity (463.3 mAh g-1),
      excellent rate performance, and considerable cycling stability. Our exploration
      not only develops a promising electrode material for SIBs, but also extends the
      application of open-framework chalcogenides.

PMID- 29445428
TI  - The Danger Zone in the Anterior Neck: Anatomical Landmarks to Avoid Injury to
      Anterior Jugular Vein During Face-Lift and Neck-Lift.
AB  - Background: An estimated 125,711 face-lifts and 54,281 neck-lifts were performed
      in 2015. Regardless of the technique employed, facial and neck flap elevation
      carries with it anatomical risk of which any surgeon performing these procedures
      should be aware of. Statistics related to anterior jugular vein injury during
      these procedures have not been published. Objective: To define a "danger zone"
      that will contain both of the anterior jugular veins on the basis of anatomical
      landmarks to aid surgeons with planning their surgical approach during
      rhytidectomy in the anterior neck region. Methods: Ten fresh tissue heminecks
      were dissected. All specimens were dissected under loupe magnification in a 45
      degrees  (face-lift) position in which a midline incision was used for exposure.
      Measurements from the anterior jugular vein to the hyoid, thyroid cartilage, and
      cricoid cartilage bilaterally were taken. The transverse distance between the
      anterior jugular veins at the level of the hyoid, thyroid cartilage, and cricoid
      cartilage was also measured. Results: The anterior jugular veins remain in an
      anatomical danger zone while they travel in the anterior neck. Regardless of
      anatomical variation of the vessels between bodies, they generally reside in this
      danger zone from their inferior emergence behind the sternocleidomastoid muscle
      until they branch in the suprahyoid region. Conclusions: Knowledge of the
      anatomy, course, and location of the anterior jugular veins through the anterior
      neck based on anatomical landmarks and distance ratios can facilitate a safer
      dissection during rhytidectomy procedures.

PMID- 29445429
TI  - Classification of MRI and psychological testing data based on support vector
      machine.
AB  - Alzheimer's disease (AD) is a progressive, and often fatal, brain disease that
      causes neurodegeneration, resulting in memory loss as well as other cognitive and
      behavioral problems. Here, we propose a novel multimodal method combining
      independent components from MRI measures and clinical assessments to distinguish
      Alzheimer's patients or mild cognitive impairment (MCI) subjects from healthy
      elderly controls. 70 AD subjects (mean age: 77.15 +/- 6.2 years), 98 MCI subjects
      (mean age: 76.91 +/- 5.7 years), and 150 HC subjects (mean age: 75.69 +/- 3.8
      years) were analyzed. Our method includes the following steps: pre-processing,
      estimating the number of independent components from the MR image data,
      extracting effective voxels for classification, and classification using a
      support vector machine (SVM)-based classifier. As a result, with regards to
      classifying AD from healthy controls, we achieved a classification accuracy of
      97.7%, sensitivity of 99.2%, and specificity of 96.7%; for differentiating MCI
      from healthy controls, we achieved a classification accuracy of 87.8%, a
      sensitivity of 86.0%, and a specificity of 89.6; these results are better than
      those obtained with clinical measurements alone (accuracy of 79.5%, sensitivity
      of 74.0%, and specificity of 85.1%). We found that (1) both AD patients and MCI
      subjects showed brain tissue loss, but the volumes of gray matter loss in MCI
      subjects was far less, supporting the notion that MCI is a prodromal stage of AD;
      and (2) combining gray matter features from MRI and three commonly used measures
      of mental status, cognitive function improved classification accuracy,
      sensitivity, and specificity compared with classification using only independent
      components or clinical measurements.

PMID- 29445430
TI  - Seizure Prophylaxis in the Immediate Post-Hemorrhagic Period in Patients with
      Aneurysmal Subarachnoid Hemorrhage.
AB  - Introduction: Seizures are a well-known complication of aneurysmal subarachnoid
      hemorrhage (aSAH) and occur most commonly in the immediate posthemorrhagic
      period. Most commonly used antiepileptic drugs (AEDs) for seizure prophylaxis in
      aSAH include phenytoin and levetiracetam. There is no reliable data available on
      the safety and efficacy of restricting AED prophylaxis only till the aneurysm is
      secured. Methods: We retrospectively chart reviewed patients admitted to our
      neurosciences intensive care unit (NICU) with aSAH during the past two years.
      Seizure incidence was studied in patients treated with phenytoin versus
      levetiracetam and in patients treated for 3-7 days vs. those where AED was
      discontinued immediately after aneurysm was secured. Results: In 28 patients, AED
      prophylaxis was discontinued immediately after the aneurysm was secured, and in
      21 patients, it was continued for 3-7 days. Of the 28 patients who received AED
      prophylaxis for less than or equal to two days, phenytoin was used in 20 patients
      and levetiracetam was used in eight patients. In patients receiving AED
      prophylaxis for 3-7 days, phenytoin was used in eight cases and levetiracetam was
      used in 13 cases. None of these patients had seizures reported during
      hospitalization or at three-month follow-up. Conclusion: Stopping the AED
      prophylaxis immediately after aneurysm coiling is not associated with increased
      risk of seizures. Seizures at presentation in patients with aSAH are not
      associated with development of epilepsy at three months. Both phenytoin and
      levetiracetam are well tolerated in patients with aSAH when limited to the
      immediate posthemorrhagic period.

PMID- 29445431
TI  - Outcome, Recurrence and Mortality after Non-Valvular Atrial Fibrillation Stroke:
      Long-Term Follow-Up Study.
AB  - Objective: Non-valvular atrial fibrillation (NVAF) is a major risk factor for
      ischemic stroke (IS) and a powerful predictor of mortality. This study
      investigates early and long-term outcome among patients with IS secondary to NVAF
      and identify the main factors associated with poor outcome, recurrence, and
      death. Methods: We analyzed the data from our consecutive NVAF acute IS database,
      over a period of 23 years. The endpoints were bad outcome (Modified Rankin Score
      >=3), recurrence, and mortality at discharge, after 6 months, 12 months, and
      final follow-up. Multivariate Cox and Kaplan-Meier analysis were used to estimate
      the probability of death. Results: 129 consecutive acute IS patients were
      included (77 [59.7%] females, mean age 70.2 +/- 10.1 years). Discharge, 6 and 12
      months bad outcome was 62%, 63%, and 61%, respectively. After a median follow-up
      of 17 months (IQR 6-54.5), 35.6% patients had bad outcome, 21.7% had recurrence
      and 36.4% died. The recurrence and death annual rates were 19.1% and 6.32%. The
      absence of oral anticoagulation (OAC) and NIHSS score > 12 were the strongest
      predictors of mortality. Conclusions: IS secondary to NVAF has a high rate of
      stroke recurrence and mortality in our population, with the absence of OAC and
      major stroke as the main risk factors.

PMID- 29445432
TI  - Recurrent Intracerebral Hemorrhage after Exercise in a Young Patient Presenting
      with Sporadic Cerebral Amyloid Angiopathy in a Young Patient.
AB  - Cerebral Amyloid Angiopathy (CAA) is one of the significant causes of lobar
      intracerebral hemorrhage (ICH) mainly among elderly people. Sporadic cases of CAA
      have been linked to genetic polymorphisms with an increased risk of disease, an
      earlier presentation, and an accelerated pathology [1]. Here, we present a
      patient with no significant risk factors who had a recurrent intracerebral
      hemorrhage secondary to CAA probably induced by exercise.

PMID- 29445433
TI  - Upright Catheter-Based Cerebral Angiography.
AB  - Background: Several studies using Doppler ultrasound have suggested cerebral
      venous drainage is through paravertebral venous plexus due to the collapse of
      internal jugular veins in an upright position. Methods: We present a technique of
      acquiring venographic images during an upright position as part of catheter-based
      angiography to provide additional information regarding cerebral venous diseases.
      Angiographic images in anteroposterior projection were acquired in lying position
      and after patients were placed at 60 degrees  using radiolucent supporting wedges
      on angiographic table. Results: In the first patient, there was activation of the
      paravertebral venous plexus as supplemental venous drainage to right internal
      jugular vein and stenosis of left internal jugular vein in high cervical segment
      in the upright position. There was relative collapse of both internal jugular
      veins in the mid-cervical region. In the second patient, there was attenuation of
      contrast opacification of right posterior cervical veins and complete occlusion
      of right internal jugular vein proximal extracranial segment (high-grade stenosis
      in lying position). There was activation of additional supplemental drainage to
      left internal jugular vein including paravertebral venous plexus. In the third
      patient, there was exacerbation of stenoses of the left and right internal
      jugular veins proximal extracranial segment in the upright position (moderate
      stenoses in lying position). There was activation of additional supplemental
      drainage via paravertebral venous plexus to both internal jugular veins.
      Conclusion: Our results demonstrate prominent changes in venous drainage patterns
      during upright angiographic images. Further studies would have to identify the
      patients in whom additional information in the upright angiography may provide
      clinically relevant information.

PMID- 29445434
TI  - Primary Endovascular Treatment of Acute Ischemic Stroke Using Stent Retrievers:
      Initial Egyptian Experience.
AB  - Background: Several mechanical thrombectomy (MT) devices have been designed with
      the goal of improving the recanalization rates of major intracranial artery
      occlusions. Objective: In this single-center experience, we analyzed the acute
      ischemic stroke (AIS) treatment with Primary MT; safety and efficacy and clinical
      results in our patients with large vessel occlusion (LVO). Methods: During a five
      year period (from September 2011 to July 2016), out of 996 patients who presented
      to our center with a diagnosis of AIS, 113 (11.4%) patients (55 men and 58 women)
      underwent primary mechanical recanalization within three hours from onset of
      signs and symptoms for anterior and 12 hours for posterior circulation (with
      computer tomography angiography/perfusion ELVO). Successful recanalization
      (thrombolysis in cerebral infarction 2b-3), good outcome (modified Rankin scale
      score 0-2) and overall mortality rate, and symptomatic intracranial hemorrhage
      [sICH: parenchymal hematoma Type 1 or Type 2; National Institutes of Health
      Stroke Scale (NIHSS) score increment >=4 points] were prospectively assessed.
      Results: The mean age of the patients was 62 +/- 11.73 years, with a baseline
      mean admission NIHSS score of 16.7 +/- 3.2. The mean time from onset to puncture
      (time to treatment) was 208.55 +/- 53.49. Successful recanalization was achieved
      in 104 (92%) cases. Good outcome was observed in 89 (78.8%) patients, and
      mortality was 11.5% (n = 13). sICH occurred in five (4.4%) patients. Conclusion:
      MT, within the first 4.5 hours, as primary treatment of acute LVO stroke provides
      high rate of recanalization and favorable clinical outcomes with low procedural
      complications.

PMID- 29445435
TI  - Investigation of Gender Differences and Exclusive Criteria in a Diabetic Acute
      Ischemic Stroke Population Treated with Recombinant Tissue-Type Plasminogen
      Activator (rtPA).
AB  - Background: Many studies have reported that women who survive stroke have less
      favorable outcomes than men in the use of rtPA, while others reported worse
      outcomes in men than women. The gender difference in the exclusion criteria in a
      diabetic stroke population is not fully understood. This issue was investigated
      in this study. Method: In a diabetic stroke population from a stroke registry of
      data collected between January 2010 to June 30, 2016, the gender difference was
      determined using demographics and clinical factors. Comparison was determined
      using univariate analysis while multivariable model was used to adjust for the
      effect of confounding variables. Results: In a diabetic stroke population of 439
      patients, more females were excluded than males (P < 0.0001, OR = 2.323). The
      male exclusion was associated with atrial fibrillation (P = 0.011, OR = 3.697),
      carotid artery stenosis (P = 0.023, OR = 5.001), and cholesterol reducer (P =
      0.037, OR = 0.409). In the female diabetic stroke population, exclusion from rtPA
      therapy was associated with language disturbances (P = 0.039, OR = 0.372),
      history of previous stroke (P = 0.005, OR = 3.276), antihypertensive medication
      use (P = 0.013, OR = 0.163), and antidiabetic medication use (P = 0.031, OR =
      0.324). Conclusion: In a stroke population, women have a worse outcome than men
      in an untreated acute ischemic stroke population, but when treated there is no
      significant difference, suggesting a better treatment outcome for women compared
      to men. In a diabetic stroke population, the clinical variables for the exclusion
      criteria for women and men are significantly different, even after adjustment for
      confounding variables.

PMID- 29445436
TI  - Steroid Responsive Encephalopathy Associated with Autoantibodies to
      Thyroperoxidase (STREAT), Presenting with Acute Stroke in a Young Female Patient.

PMID- 29445437
TI  - Delayed Coil Migration: Uncommon Cause of Ischemic Stroke and Retrieval
      Technique.

PMID- 29445438
TI  - Vertebral Artery Origin Stent Placement Using the Dual Lumen Qureshi-Jiao
      Guidecatheter.
AB  - Objective: We report the first experience with a new dual lumen guide catheter
      with lumen A with curved tip designed for delivery of stent and angioplasty
      catheters and lumen B with side exit for coaxial placement of stiff 0.014 inch
      wire. Methods: We prospectively determined technical success, intended procedure
      (stent delivery at target lesion and a final residual stenosis <30%) completed
      without a need for a different catheter, and technical ease, intended procedure
      completed without >=3 unsuccessful attempts in patients with symptomatic
      vertebral artery origin stenosis. Vertebral artery origin was classified as type
      A if originated from ascending segment and type B if originated from an arch or
      horizontal segment of subclavian artery. Results: The mean age of the four
      treated patients was 66.2 years (range 64-68 years). The mean percentage of
      vertebral artery origin stenosis was 82.7% (range 60-92%). The origin of
      vertebral artery from subclavian artery was classified as type A and type B
      origins in two patients each. The dual lumen catheter was advanced over an
      exchange length of 0.035 inch glide wire in one patient and directly through
      transfemoral insertion in three patients. Technical success and technical ease
      was achieved in all four procedures. Post procedure residual stenosis was 6%
      (range 5-7%). The primary operator rated the performance of guide catheter as
      superior compared with another catheter used in such procedures. Conclusion: The
      present study demonstrates the feasibility of performing stent placement for
      vertebral artery origin stenosis by using a dual lumen catheter with superior
      performance.

PMID- 29445439
TI  - Severe reversible cerebral vasoconstriction syndrome in a postpartum patient
      treated successfully with direct instillation of intra-arterial verapamil during
      cerebral angiography.

PMID- 29445440
TI  - Comparison of Clinical and Radiological Outcome of Carotid Angioplasty and
      Stenting after Direct Navigation Versus Exchange Methods: A Randomized Clinical
      Trial.
AB  - Background: The purpose of this study was to compare the frequency of
      microembolic brain infarcts after direct navigation method versus exchange method
      in carotid artery stenting and vertebral artery origin angioplasty. Methods and
      Material: This is a prospective study conducted at Shiraz University of Medical
      Sciences in southern Iran. Consecutive patients undergoing "carotid angioplasty
      and stenting" and "vertebral artery origin stenting" were randomly assigned into
      two groups with "direct navigation method" and "exchange method." Subsequently,
      postprocedural magnetic resonance imaging (MRI) including diffusion weighted
      imaging and apparent diffusion coefficient were obtained within the first 24
      hours after completion of the procedure. Results: In total, 89 patients were
      recruited (67% male, mean age: 72 years). Cases comprised of 38 left internal
      carotid arteries (ICAs), 38 right ICAs, 6 left vertebral artery origin, and 7
      right vertebral artery origin. Forty patients underwent exchange method, while 49
      underwent direct navigation method. There was only one clinical stroke that
      occurred in "exchange method" group. Fifteen patients (37.5%) in exchange group
      and 23 patients (46.9%) in direct navigation group developed diffusion restricted
      lesions. In exchange group, 13 patients (32.5%) had at least one diffusion
      restricted lesion ipsilateral to the target vessel, and three patients (7.5%) had
      at least one diffusion restricted lesion contralateral to the target vessel. In
      direct navigation group, these measures were 19 (38.8%) and 9 (18.4%). However,
      no statistically significant intergroup differences were observed. The only
      significant difference was bilateral infarct percentile, which was more common in
      the direct navigation method (0.032). Conclusion: Diffusion restricted lesions
      were more common in the direct navigation method, both ipsilateral and
      contralateral to the target vessel, and in both carotid and vertebral artery
      study subgroups. However, differences were not statistically significant.

PMID- 29445441
TI  - Potential New Cysteine Sparing Mutation in the NOTCH3 Gene in a Patient with
      Nonfamilial CADASIL-like Disease.
AB  - Background: Several different mutations have been reported in patients with
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL). We present a unique case with transversion not
      involving cysteine on neurogenic locus notch homolog protein 3 gene. Case
      description: We present a case of 65-year-old woman with new ischemic stroke
      resulting in right hemiparesis. She has previously suffered minor strokes at age
      56, 58, and 60 years and migraine headaches between age 10 and 50 years. Magnetic
      resonance imaging demonstrated multifocal chronic ischemic infarctions with
      encephalomalacia in the left posterior parietal, parieto-occipital regions and
      the pons. An analysis of the protein sequence of notch 3 gene did not demonstrate
      any alterations characteristics of CADASIL disease. There was a deoxyribonucleic
      acid variant with transversion of alanine with tyrosine and change of histidine
      with leucine on notch 3 gene. None of the family members had any clinical
      manifestations suggestive of CADASIL. Conclusion: We report the first report of
      deoxyribonucleic acid variation in notch 3 gene associated with clinical features
      of CADASIL without any familial component.

PMID- 29445442
TI  - Cerebral Angiography in Moyamoya Syndrome Secondary to Vasculopathy in Down
      Syndrome.

PMID- 29445443
TI  - Artery of Trigeminal Nerve Ganglion.
AB  - The artery to trigeminal nerve ganglion has been identified as a branch that
      arises from the extracranial segment of middle meningeal artery prior to entry
      into the foramen spinosum. The role of the artery in being the arterial supply to
      trigeminal nerve ganglion is supported by electrophysiological and clinical
      suppression of trigeminal nerve activity during selective intra-arterial
      injection of anesthetics.

PMID- 29445444
TI  - Corrigendum to "Resolving Contributions of Oxygen-Consuming and ROS-Generating
      Enzymes at the Synapse".
AB  - [This corrects the article DOI: 10.1155/2016/1089364.].

PMID- 29445446
TI  - Down-regulation of miR-210-3p encourages chemotherapy resistance of renal cell
      carcinoma via modulating ABCC1.
AB  - Background: ATP-binding cassette transporter super-family including ABCC1 and MDR
      1 were involved in multi-drug resistance (MDR) of renal cell carcinoma (RCC)
      patients. Several miRNAs were confirmed to promote the MDR and the survival of
      tumor cells. Methods: The RCC cell lines Caki-2 with vinblastine-resistant (Caki
      2/VBL) or doxorubicin-resistant (Caki-2/DOX) were constructed, respectively. The
      expressions of miR-210-3p, ABCC1 and MDR-1 protein were determined by qRT-PCR and
      Western blot assays. The viability of RCC cells was assessed by MTT assay. The
      regulatory relationship between miR-210-3p and ABCC1 was analyzed by Dual
      Luciferase assay. The effect of miR-210-3p in vivo was investigated with a tumor
      xenograft model in mice. Results: MiR-210-3p expression was observed to
      significantly decrease in Caki-2/VBL and Caki-2/DOX cells. Meanwhile, ABCC1 and
      MDR-1 were significantly increased in Caki-2/VBL and Caki-2/DOX cells. ABCC1 was
      a novel target of miR-210-3p and negatively regulated by miR-210-3p. And miR-210
      3p improved drug-sensitivity of RCC cells. Down-regulation of ABCC1 could reverse
      the effect of miR-210-3p knockdown on the drug-resistance and the level of MDR-1
      in drug-sensitive RCC cells. Conclusion: We confirmed that down-regulation of miR
      210-3p increased ABCC1 expression, thereby enhancing the MRP-1-mediated multidrug
      resistance of RCC cells.

PMID- 29445447
TI  - Pre-hospital delay in Vietnamese patients hospitalized with a first acute
      myocardial infarction: A short report.
AB  - Background Administration of coronary reperfusion therapy to patients with an
      acute myocardial infarction (AMI) within the proper timeframe is essential in
      avoiding clinical complications and death. However, the extent of pre-hospital
      delay is unexplored in Vietnam. This report aims to describe the duration of pre
      hospital delay of Hanoi residents hospitalized with a first AMI at the Vietnam
      National Heart Institute . Methods A total of 103 Hanoi residents hospitalized at
      the largest tertiary care medical center in the city for first AMI, who have
      information on  prehospital delay was included in this report. Results One third
      of the study sample was women and mean age was 66 years. The mean and median pre
      hospital delay duration were 14.9 hours and 4.8 hours, respectively. The
      proportion of patients who delayed <6 , 6-<12, and >= 12 hours were 45%, 13%, and
      42%, respectively. Conclusions Our data shows that a prolonged pre-hospital delay
      is often observed in patients with a first AMI in Vietnam. In order to confirm
      these findings, a full-scale investigation of all Hanoi residents hospitalized
      with first AMI is needed. Increasing public awareness about AMI treatment is
      vital in encouraging patients to seek medical care timely after experiencing AMI
      symptoms such that received treatment is most effective.

PMID- 29445445
TI  - Fe-S Clusters Emerging as Targets of Therapeutic Drugs.
AB  - Fe-S centers exhibit strong electronic plasticity, which is of importance for
      insuring fine redox tuning of protein biological properties. In accordance, Fe-S
      clusters are also highly sensitive to oxidation and can be very easily altered in
      vivo by different drugs, either directly or indirectly due to catabolic by
      products, such as nitric oxide species (NOS) or reactive oxygen species (ROS). In
      case of metal ions, Fe-S cluster alteration might be the result of metal
      liganding to the coordinating sulfur atoms, as suggested for copper. Several
      drugs presented through this review are either capable of direct interaction with
      Fe-S clusters or of secondary Fe-S clusters alteration following ROS or NOS
      production. Reactions leading to Fe-S cluster disruption are also reported. Due
      to the recent interest and progress in Fe-S biology, it is very likely that an
      increasing number of drugs already used in clinics will emerge as molecules
      interfering with Fe-S centers in the near future. Targeting Fe-S centers could
      also become a promising strategy for drug development.

PMID- 29445448
TI  - Surgical placement of a wireless telemetry device for cardiovascular studies of
      bovine calves.
AB  - Background: Domestic cattle ( Bos taurus) are naturally susceptible to hypoxia
      induced pulmonary arterial hypertension; consequently, the bovine calf has been
      used with considerable success as an animal model of the analogous human
      condition. Studies to date, however, have relied on instantaneous measurements of
      pressure and cardiac output. Here, we describe the surgical technique for
      placement of a fully implantable wireless biotelemetry device in a bovine calf
      for measurement of pulmonary arterial and left ventricular pressures, right
      ventricular output, and electrocardiogram. Methods: Three, 2-month old bovine
      calves underwent left-sided thoracotomies. A transit-time flow probe was placed
      around the pulmonary artery and solid-state pressure catheters inserted into the
      pulmonary artery and left ventricle. Biopotential leads were secured to the
      epicardium. The implant body was secured subcutaneously, dorso-caudal to the
      incision. Results: The implant and sensors were successfully placed in two of the
      three calves. One calf died from ventricular fibrillation following left
      ventricular puncture prior to pressure sensor insertion. Anatomical discrepancies
      meant that either 4 th or 5 th rib was removed. The calves recovered quickly with
      minimal complications that included moderate dyspnea and subcutaneous edema.
      Conclusions: Left thoracotomy is a viable surgical approach for wireless
      biotelemetry studies of bovine calf cardiovascular function. The real-time,
      contemporaneous collection of cardiovascular pressures and output, permits
      pathophysiological studies in a naturally susceptible, large animal model of
      pulmonary arterial hypertension.

PMID- 29445449
TI  - Early language development in preterm children without neurological damage: a
      longitudinal study.
AB  - Children born at a very low gestational age, even those without neurosensory
      damages, are at risk of linguistic disorders. This longitudinal study aimed at
      analyzing communicative and language abilities in preterm children during their
      second year of life, through a standardized questionnaire, with particular
      attention to the communicative and language abilities that predict the first
      verbal skills. Our results showed that preterm children are slower than full
      terms in language acquisition particularly at earlier stages of development. The
      differences between the two groups of children was significant only at 16 and 18
      months. Preterms use more simplistic linguistic categories for longer than full
      terms, with regards to lexicon composition and syntactic complexity. This
      different pattern could involve more qualitative, rather than quantitative,
      aspects of developmental processes that characterize language acquisition in
      preterms and full-term children.

PMID- 29445450
TI  - Prevention of influenza-related illness in young infants by maternal vaccination
      during pregnancy.
AB  - The influenza virus circulates yearly and causes global epidemics. Influenza
      infection affects all age groups and causes mild to severe illness, and young
      infants are at particular risk for serious disease. The most effective measure to
      prevent influenza disease is vaccination; however, no vaccine is licensed for use
      in infants younger than 6 months old. Thus, there is a crucial need for other
      preventive strategies in this high-risk age group. Influenza vaccination during
      pregnancy protects both the mothers and the young infants against influenza
      infection. Vaccination during pregnancy boosts the maternal antibodies and
      increases the transfer of immunoglobulin G from the mother to the fetus through
      the placenta, which confers protection against infection in infants too young to
      be vaccinated. Data from clinical trials and observational studies did not
      demonstrate adverse effects to the mother, the fetus, or the infant after
      maternal influenza vaccination. We present the current data on the effectiveness
      and safety of influenza vaccination during pregnancy in preventing disease in the
      young infant.

PMID- 29445451
TI  - Recent progress on the molecular pharmacology of propofol.
AB  - The precise mechanism by which propofol enhances GABAergic transmission remains
      unclear, but much progress has been made regarding the underlying structural and
      dynamic mechanisms. Furthermore, it is now clear that propofol has additional
      molecular targets, many of which are functionally influenced at concentrations
      achieved clinically. Focusing primarily on molecular targets, this brief review
      attempts to summarize some of this recent progress while pointing out knowledge
      gaps and controversies. It is not intended to be comprehensive but rather to
      stimulate further thought, discussion, and study on the mechanisms by which
      propofol produces its pleiotropic effects.

PMID- 29445453
TI  - The European Falsified Medicines Directive in Poland: background, implementation
      and potential recommendations for pharmacists.
AB  - By February 2019, the Polish pharmaceutical industry, community and hospital
      pharmacies, wholesalers and parallel traders must all comply with the EU-wide
      Falsified Medicines Directive (FMD) legislation (2011/62/EU), to ensure that no
      medicinal product is dispensed to a patient without proper tracking and
      authentication. Here we describe how Poland is complying with the new EU
      regulations, the actions that have been taken to incorporate the FMD into Polish
      Pharmaceutical Law and whether or not these actions are sufficient. We found that
      Poland is only partially compliant with the FMD and further actions need to be
      undertaken to fully meet the Delegated Act (DA) requirements. Moreover, there is
      lack of awareness in Poland about the prevalence of falsified medication and the
      time scale required for implementation of the DA. Based on our findings, we
      suggest that a public awareness campaign should be started to raise awareness of
      the increased number of falsified medicines in the legal supply chain and that
      drug authorisation systems are implemented by Polish pharmacies to support the
      FMD.

PMID- 29445452
TI  - Exploiting immune cell metabolic machinery for functional HIV cure and the
      prevention of inflammaging.
AB  - An emerging paradigm in immunology suggests that metabolic reprogramming and
      immune cell activation and functions are intricately linked. Viral infections,
      such as HIV infection, as well as cancer force immune cells to undergo major
      metabolic challenges. Cells must divert energy resources in order to mount an
      effective immune response. However, the fact that immune cells adopt specific
      metabolic programs to provide host defense against intracellular pathogens and
      how this metabolic shift impacts immune cell functions and the natural course of
      diseases have only recently been appreciated. A clearer insight into how these
      processes are inter-related will affect our understanding of several fundamental
      aspects of HIV persistence. Even in patients with long-term use of anti
      retroviral therapies, HIV infection persists and continues to cause chronic
      immune activation and inflammation, ongoing and cumulative damage to multiple
      organs systems, and a reduction in life expectancy. HIV-associated fundamental
      changes to the metabolic machinery of the immune system can promote a state of
      "inflammaging", a chronic, low-grade inflammation with specific immune changes
      that characterize aging, and can also contribute to the persistence of HIV in its
      reservoirs. In this commentary, we will bring into focus evolving concepts on how
      HIV modulates the metabolic machinery of immune cells in order to persist in
      reservoirs and how metabolic reprogramming facilitates a chronic state of
      inflammation that underlies the development of age-related comorbidities. We will
      discuss how immunometabolism is facilitating the changing paradigms in HIV cure
      research and outline the novel therapeutic opportunities for preventing
      inflammaging and premature development of age-related conditions in HIV +
      individuals.

PMID- 29445455
TI  - Postnatal care utilization and associated factors among women of reproductive age
      Group in Halaba Kulito Town, Southern Ethiopia.
AB  - Background: Despite postnatal care services significant role in improving
      maternal and new-born health, services are underutilized in most developing
      countries including Ethiopia. Hence, it is important to identify factors that
      facilitate or impede postnatal care services utilization. The aim of this study
      was to assess postnatal care services utilization and associated factors among
      reproductive age women who gave live birth in 2015 at Halaba kulito town,
      Southern Ethiopia. Methods: A community-based cross-sectional study was conducted
      on 401 reproductive age women who gave live birth a year prior to the survey.
      Data were collected by using structured questionnaire. Bivariate and
      multivariable logistic regression analysis were carried out to identify factors
      associated with postnatal care services utilization. A significant association
      was declared when p-value is less than 0.05. The strength of association was
      determined by calculating odds ratio at 95% confidence interval. Result: In this
      study, postnatal care services utilization by reproductive age women was 47.9%.
      Multivariable analysis revealed that government employed (AOR = 3.01, 95%CI =
      1.36, 6.67), have three ANC visits (AOR = 4.29, 95% CI = 1.59, 11.55), have four
      ANC visits (AOR = 9.55, 95% CI = (3.46, 26.39), gave last birth at Health Centre
      (AOR = 10.76, 95% CI = 3.26, 35.57), gave last birth at Hospital (AOR = 13.15,
      95% CI = (3.64, 47.50), didn't aware of at least one postpartum danger signs (AOR
      = 0.06, 95% CI = (0.01, 0.37), didn't know child care and had three ANC visits
      (AOR =0 .14, 95% CI (0.02, 0.8), and didn't know child care and had four or more
      ANC visits (AOR =0 .13, 95% CI (0.02, 0.79) were significantly associated with
      postnatal care services utilization. Conclusion: This study assessed PNC services
      utilization and associated factors among reproductive age women. The study
      results provided a basic understanding of factors that associated with PNC
      services utilization by reproductive age women. The findings of this study showed
      direct association between postnatal care utilization and maternal employment,
      awareness to postpartum danger signs, frequency of ANC and attending birth at
      health institution. Therefore, the results suggested context-specific evidence
      which might be taken into consideration when rethinking policies to increase PNC
      utilization.

PMID- 29445454
TI  - Rumen-protected methionine during the peripartal period in dairy cows and its
      effects on abundance of major species of ruminal bacteria.
AB  - Background: Extensive degradation of amino acids in the rumen via microbial
      deamination decreases the post-ruminal availability of dietary indispensable
      amino acids. Together with the normal decrease in voluntary dry matter intake
      (DMI) around parturition in dairy cows, microbial metabolism contributes to a
      markedly negative balance of indispensable amino acids, including methionine
      which may be the first-limiting for milk production. The main objective of the
      current study was to profile changes in major bacterial species with key
      functions in cellulose and hemicellulose digestion, xylan breakdown, proteolytic
      action, propionic acid production, lactate utilization and ruminal
      biohydrogenation in cows supplemented with rumen-protected Methionine (SM;
      Smartamine M, Adisseo NA, Alpharetta, GA, USA) from -23 through 30 d relative to
      parturition. Because ~90% of the methionine in SM bypasses the rumen, ~10% of the
      methionine is released into the rumen and can be utilized by microbes. Results:
      As expected, there was an increase in overall DMI after parturition (Day, P <
      0.05) during which cows consumed on average 19.6 kg/d versus 13.9 kg/d in the
      prepartum period. The postpartum diet contained greater concentrations of lipid
      and highly-fermentable carbohydrate from corn grain, which likely explains the
      increases in the relative abundance of Anaerovibrio lipolytica, Megasphaera
      elsdenii, Prevotella bryantii, Selenomonas ruminantium, Streptococcus bovis, and
      Succinimonas amylolytica. Despite similar DMI prepartum, cows fed SM had greater
      (Treatment * Day, P < 0.05) abundance prepartum of Fibrobacter succinogenes,
      Succinimonas amylolytica, and Succinivibrio dextrinosolvens. However, the greater
      DMI in cows fed SM after parturition (19.6 kg/d versus 13.9 kg/d) was associated
      with lower abundance of Fibrobacter succinogenes (2.13 * 10-3 versus 2.25 * 10-4)
      and Selenomonas ruminantium (2.98 * 10-1 versus 4.10 * 10-1). A lower abundance
      (Day, P < 0.05) was detected on d 20 compared with d -10 for Fibrobacter
      succinogenes and Succinivibrio dextrinosolvens. The relative abundance of
      Butyrivibrio proteoclasticus and Eubacterium ruminantium was stable across
      treatment and time. Conclusions: In diets with proper balance of rumen-degradable
      protein and fermentable carbohydrate, the small fraction of Methionine released
      from the rumen-protected supplement did not seem to compromise growth of major
      bacterial species in the rumen. In fact, it had a positive effect on 3 major
      species prepartum when DMI was similar between groups. Because the actual
      requirements of Methionine (and Lysine, for example) by the cow during the
      transition period are unknown, it appears warranted to study the rumen microbiome
      as it relates to supply of rumen-protected amino acids.

PMID- 29445457
TI  - Prostate carcinoma presenting with diffuse osteolytic metastases and
      supraclavicular lymphadenopathy mimicking multiple myeloma.
AB  - Prostate cancer typically presents with osteoblastic metastases; however,
      patients with prostate cancer may have osteolytic metastases, as seen in this
      case. Patients with osteolytic metastases require a thorough evaluation to rule
      out malignancies including multiple myeloma, but prostate cancer is a very
      important differential diagnosis.

PMID- 29445456
TI  - Suture-induced arthritis as a clinical mimicker of septic arthritis.
AB  - Foreign body-induced arthritis is a rare etiology of mono-arthritis. It should be
      suspected in the case of postoperative arthritis, even if some decades have
      passed since surgery. Histopathology of the tissues is required for a definitive
      diagnosis, and debridement is essential for complete recovery.

PMID- 29445458
TI  - Stevens-Johnson syndrome/toxic epidermal necrolysis associated with zonisamide.
AB  - This report highlights zonisamide as a potential cause of serious cutaneous
      reactions as well as its cross-reactivity with other sulfonamides. Here, we
      present a case of SJS-TEN due to zonisamide, which was effectively treated with
      IVIg. Subsequently, the patient was transitioned to levetiracetam for seizure
      control.

PMID- 29445459
TI  - Parotid swelling after Russell's viper envenomation: an unusual and poor
      prognostic sign.
AB  - Parotid swelling, an unusual and poorly understood sign, is associated with poor
      prognosis in the setting of Russell's viper envenomation. The large, aggressive
      Russell's viper is one of the most deadly snakes causing severe hematological and
      neurological manifestations. Research into this sign should be initiated and
      understanding could lead to improved outcomes.

PMID- 29445460
TI  - Case report: photo-onycholysis after PUVA treatment for hypopigmented mycosis
      fungoides with response to topical steroid.
AB  - Melanin in the nail bed in patients with skin type VI has been suggested to
      afford some protection against photo-onycholysis. We report a case of a 16-year
      old male patient with skin type VI with onycholysis following PUVA treatment for
      hypopigmented mycosis fungoides. Symptoms resolved with the application of
      topical steroid.

PMID- 29445461
TI  - Metastatic prostate cancer with bone marrow infiltration mimicking multiple
      myeloma.
AB  - Concomitant diagnosis of metastatic prostate cancer and a multiple myeloma in
      older male patients is challenging as both malignancies are usually associated
      with bone lesions. Exact knowledge, experience, and an interdisciplinary approach
      are required in order to differentiate between both malignancies and determine
      the exact treatment strategy.

PMID- 29445462
TI  - A low-grade astrocytoma in a sixteen-year-old boy with a 7q11.22 deletion.
AB  - We report a patient with developmental delay due to germline AUTS2 mutation who
      developed a low-grade astrocytoma. While the contribution of this mutation to the
      pathogenesis of the tumor is not known at this time, a role of AUTS2 in
      deregulation of PRC1 can be a part in tumorigenesis of a brain tumor.

PMID- 29445463
TI  - Resolving bulimia nervosa using an innovative neural therapy approach: two case
      reports.
AB  - Conventional treatment of Bulimia Nervosa is long term, expensive, and often
      ineffective. Neural therapy holds promise for treating Bulimia Nervosa in a
      shorter term, lower cost, and more effective manner. Much of neural therapy
      involves the superficial injection of local anesthetic injections. Implementation
      into current practice would be feasible.

PMID- 29445464
TI  - Takotsubo syndrome-associated ventricular standstill in a peripartum patient:
      case report and review of the literature.
AB  - Takotsubo syndrome is classically characterized by apical ballooning and left
      ventricle akinesis associated with an underlying catecholamine surge. In patients
      with suspected Takotsubo syndrome, clinicians should be vigilant for acute
      coronary syndrome and arrhythmias. Ventricular standstill with underlying
      Takotsubo syndrome should be managed with a dual-chambered pacemaker to improve
      patient outcome.

PMID- 29445465
TI  - The physiotherapeutic "Variable Approach Technique": an example of neuromotor
      adaptation conveyed by the neuromuscular spindle.
AB  - The subcortical systems control the proper functioning of the automatic substrate
      required for movement. Such a substrate is often underestimated to give attention
      to voluntary movement. By applying Variable Approach technique, it is possible to
      communicate with automatic systems through muscular spindles to achieve a more
      functional volunteer movement.

PMID- 29445466
TI  - Oral nerve sheath myxoma: a rare and unusual intraoral neoplasm.
AB  - We present a rare case of intraoral nerve sheath myxoma. Clinically, the neoplasm
      mimics many other oral mucosal pathosis, underscoring the importance of
      histopathology in ensuring accurate diagnosis of oral mucosal lesions. Reports of
      intraoral nerve sheath myxomas are essential to enhance our understanding of this
      rare intraoral entity.

PMID- 29445467
TI  - Chronic aortic dissection with tricuspid regurgitation: report of a case.
AB  - Dilatation of aortic root may distort the tricuspid annulus. We experienced a
      case of chronic aortic dissection presented with tricuspid regurgitation. Chest
      computed tomography revealed an enlarged ascending aorta displacing the right
      heart. The patient successfully underwent replacement of the aorta and tricuspid
      annuloplasty with a prosthetic annulus.

PMID- 29445468
TI  - Routine exercise testing could not predict T-wave oversensing in a patient after
      a subcutaneous implantable cardioverter-defibrillator implant.
AB  - Subcutaneous implantable cardioverter-defibrillators (S-ICDs) are susceptible to
      T-wave oversensing (TWOS) caused by high rate-dependent QRS-T morphology changes.
      We experienced an inappropriate S-ICD shock due to TWOS, which could not be
      predicted by routine exercise testing. A newly available high-pass filter might
      be effective for avoiding this.

PMID- 29445469
TI  - Spontaneous pneumomediastinum in a term neonate - case report.
AB  - Pneumomediastinum after birth, without birth injury or resuscitation maneuvers,
      is an unusual situation that can present with grunting, deafening of cardiac
      sounds, and bulging of the hemithorax. If clinical condition allows, conservative
      approach is advised even if the pneumomediastinum does not spontaneously resolve
      in 1 or 2 days.

PMID- 29445470
TI  - Emergency transcatheter closure of a stented PDA in a patient with pulmonary
      atresia and intact ventricular septum: be ready for the unexpected!
AB  - Patients with congenital heart disease and duct-dependent pulmonary circulation
      can undergo stenting of the patent ductus arteriosus (PDA). This case shows that,
      due to the physiological changes occurring after stent implantation, sometimes it
      is necessary to close the stented PDA rather than to redilate it.

PMID- 29445471
TI  - Superior mesenteric artery syndrome: quality of life after laparoscopic
      duodenojejunostomy.
AB  - In this study, we present results after laparoscopic duodenojejunostomy for five
      patients with protracted superior mesenteric artery syndrome. The procedure can
      be performed with minimal perioperative risk and very short postoperative stay.
      It provides significant postoperative symptom relief for many patients with
      typical presentation of the syndrome.

PMID- 29445472
TI  - Mild prominence of the Sylvian fissure in a Bainbridge-Ropers syndrome patient
      with a novel frameshift variant in ASXL3.
AB  - A Japanese boy aged 7 years with Bainbridge-Ropers syndrome (BRPS) had a
      prominent domed forehead without metric ridge, mild prominence of the Sylvian
      fissure with bitemporal hollowing, and a heterozygous de novo novel variant
      "p.P1010Lfs*14" in ASXL3 gene in addition to typical findings of BRPS.

PMID- 29445473
TI  - Graves' disease coexisting with resistance to thyroid hormone: a rare case.
AB  - A rare case of resistance to thyroid hormone (RTH) complicated with Graves'
      hyperthyroidism was reported. The management of this disease is similar to that
      of Graves' disease. Antithyroid drug therapy is the first choice, and iodine
      therapy and surgery are not recommended due to the possibility of severe
      hypothyroidism and enlargement of the pituitary gland.

PMID- 29445475
TI  - Endogenous carbon monoxide production in extracorporeal membrane oxygenation
      related hemolysis: potential use of point-of-care CO-oximetry carboxyhemoglobin
      to detect hemolysis.
AB  - Extracorporeal membrane oxygenation (ECMO)-related hemolysis is a rare but
      devastating condition. Death is inevitable without early recognition and prompt
      management. Endogenous carbon monoxide production, as an epiphenomenon of
      hemolysis, potentially allows rapid detection of such condition by use of point
      of-care CO-oximetry carboxyhemoglobin.

PMID- 29445474
TI  - Monochorionic diamniotic twins with centrally located and closely spaced
      umbilical cord insertions in the placenta.
AB  - When to deliver the monochorionic diamniotic (MCDA) twins with specific cord
      patterns? Although there is no clear evidence supporting an earlier delivery
      (before 36 weeks of gestation) in MCDA twins, an earlier delivery might prevent
      intrauterine death or neuromorbidity in MCDA twins with specific cord patterns.

PMID- 29445476
TI  - Eccrine porocarcinoma arising from the knee.
AB  - Enlarged eccrine porocarcinoma of the knee was encountered as a hemorrhagic bulky
      tumor. After controlling bleeding with Mohs' paste, local excision of the lesion
      was the mainstay of treatment. Pathological examination revealed poroid cells,
      cuticle cells, and prickle cells cancer components, suggesting that malignancy
      must be excluded by resection.

PMID- 29445477
TI  - Beta-propeller protein-associated neurodegeneration: a case report and review of
      the literature.
AB  - Beta-propeller protein-associated neurodegeneration (BPAN) is a rare disorder,
      which is increasingly recognized thanks to next-generation sequencing. Due to a
      highly variable phenotype, patients may present to pediatrics, neurology,
      psychiatry, or internal medicine. It is therefore essential that physicians of
      different specialties are familiar with this severe and debilitating condition.

PMID- 29445478
TI  - Azygos continuation of the caudal vena cava with segmental aneurysm, lung lobe
      torsion and pulmonary thromboembolism in a dog.
AB  - This case highlights the management and diagnostic evaluation of a dog with two
      individually rare conditions (lung lobe torsion and vena cava aneurysm) that
      ultimately resulted in fatal pulmonary thromboembolism.

PMID- 29445479
TI  - Safe surgical treatment of peripelvic renal cyst combined with renal calculi by
      percutaneous nephroscopy.
AB  - We have tried to establish a safe and effective method to treat the peripelvic
      renal cyst combined with renal calculi. The key points are as follows: choose the
      appropriate target calyx; find the gap between cyst and renal pelvic; put a
      nephrostomy tube to stimulate the closing of cystic cavity.

PMID- 29445480
TI  - Hemolytic anemia due to native valve subacute endocarditis with Actinomyces
      israelii infection.
AB  - This case highlights the importance of considering infectious etiology in the
      management of hemolytic anemia. Hemolytic anemia associated with infectious
      endocarditis is rare. Actinomyces endocarditis is a rare occurrence and is very
      challenging to diagnose given the challenges to culture the organism.

PMID- 29445481
TI  - Alleviation of thalamic pain by cilostazol administration: a case report.
AB  - Thalamic pain is severe and treatment-resistant; however, there are few available
      options for improving thalamic pain. This study demonstrated that thalamic pain
      was alleviated by administration of cilostazol, suggesting that cilostazol may be
      a candidate for treating thalamic pain.

PMID- 29445482
TI  - Successful management of a parasitic ischiopagus conjoined twins in a low-income
      setting.
AB  - Ischiopagus parasites are fetal defects attached to a relatively normal twin by
      pelvis. This is the first reported case of parasitic ischiopagus twins without
      prenatal diagnosis successfully managed in Mozambique. A multidisciplinary team
      was involved in the supernumerary limbs excision. After 7 months, the infant has
      a normal development.

PMID- 29445483
TI  - Lenalidomide decreased the PSA level for castration-resistant prostate cancer: a
      case report.
AB  - Lenalidomide has been developed as the derivative of thalidomide that has fewer
      side effects. We herein report a rare case of castration-resistant prostate
      cancer successfully maintained using lenalidomide for multiple myeloma.

PMID- 29445484
TI  - Right extrapleural completion pneumonectomy for fibrocavitary nontuberculous
      mycobacterial lung disease.
AB  - We report a case of a 76-year-old man with fibrocavitary nontuberculous
      mycobacterial (FC-NTM) lung disease, who was successfully treated with right
      extrapleural completion pneumonectomy. Right extrapleural completion
      pneumonectomy with careful coverage of the bronchial stump might be effective in
      patients with FC-NTM lung disease.

PMID- 29445485
TI  - Esophageal atresia and Beckwith-Wiedemann syndrome in one of the naturally
      conceived discordant newborn twins: first report.
AB  - Recent studies report a high incidence of monozygotic twinning in Beckwith
      Wiedemann syndrome. A phenotypical discordance in monozygotic twins is rare.
      Twinning and Beckwith-Wiedemann syndrome show higher incidence in children born
      after assisted reproductive techniques. We report on the first observation of
      esophageal atresia and Beckwith-Wiedemann syndrome in one of the naturally
      conceived discordant monozygotic twins.

PMID- 29445486
TI  - Aneurysm of the inferior vena cava with thrombosis.
AB  - Inferior vena cava (IVC) aneurysms are extremely rare. Patients can be
      asymptomatic, have thrombosis, rupture, or pulmonary embolism. Thrombosis of the
      IVC aneurysm may mimic a retroperitoneal tumor. Surgical treatment of abdominal
      venous aneurysms with thrombosis is warranted and is necessary for the management
      of intraoperative bleeding and thrombosis.

PMID- 29445487
TI  - Neonatal subcortical bruising.
AB  - A specific type of acute brain injury can occur during birth, presenting on
      ultrasound examination with focal, unilateral, or asymmetrical change in the core
      of the superior frontal gyri. Ultrasound inspection of the superior gyri near the
      convexity of the frontal lobe is warranted following mechanically difficult
      delivery.

PMID- 29445488
TI  - Glucocorticoid-remediable aldosteronism in a young adult with a family history of
      Conn's syndrome.
AB  - Glucocorticoid-remediable aldosteronism is a hereditary form of primary
      hyperaldosteronism and the most common monogenic cause of hypertension. We
      present the case of a 24-year-old man with a family history of Conn's syndrome.
      Yet, in the index patient, classical characteristics of mineralocorticoid excess
      could be reversed by exogenous glucocorticoids.

PMID- 29445489
TI  - Prenatal diagnosis of diaphanospondylodysostosis (DSD): a case report.
AB  - We present a case of diaphanospondylodysostosis (DSD) which showed increased
      nuchal translucency at 1st trimester and missing ossification of the lower spine,
      short ribs with posterior gaps, and absent nasal bone in midtrimester. Autopsy
      revealed additionally bilateral nephroblastomatosis. Molecular genetic analysis
      showed a new mutation in the BMPER gene.

PMID- 29445490
TI  - Primary growth hormone insensitivity and psychomotor delay.
AB  - We report a case of short stature irresponsive to growth hormone (GH) replacement
      therapy. Low GH response to provocative tests and undetectable IGF-1 levels had
      suggested GH deficiency, while response to therapy indicated GH insensitivity.
      Molecular evaluation of the GH/IGF-1 axis should be performed in these cases to
      improve diagnosis and therapy.

PMID- 29445491
TI  - The skin-kidney connection: bullous pemphigoid associated with acute allograft
      rejection and membranous nephropathy.
AB  - Bullous pemphigoid has been linked to allograft rejection, as well as membranous
      nephropathy in renal transplant recipients. Although there is a possibility of
      multiple distinct autoimmune processes, immune stimulation induced by allograft
      rejection or antibasement zone antibody interactions are possible mechanisms for
      the simultaneous skin and renal involvement.

PMID- 29445492
TI  - Mycoplasma pneumoniae-associated Fuchs syndrome.
AB  - Fuchs syndrome is a milder form of the Stevens-Johnson syndrome (SJS) spectrum
      with only mucosal involvement which can be triggered by Mycoplasma pneumonia (MP)
      infection. Treatment should be directed toward supportive care including ocular
      and mucous membrane care, fluids and nutritional support, and pain control. In
      addition, antibiotic and immunomodulatory treatments are discussed for this
      entity.

PMID- 29445493
TI  - Acute disseminated encephalomyelitis following Influenza A pneumonia.
AB  - Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating
      disorder of the central nervous system and can present following influenza A
      infections as multifocal neurological deficits. ADEM remains a challenging
      diagnosis, and high clinical suspicious coupled with laboratory investigations
      and neuroimaging is required to exclude other primary and secondary demyelinating
      disorders.

PMID- 29445494
TI  - Emphysematous pyelonephritis.
AB  - Emphysematous pyelonephritis is a gas-producing, necrotizing infection involving
      the renal parenchyma and surrounding tissue that is associated with high
      mortality and morbidity. Common causative organisms include Escherichia coli and
      Klebsiella pneumoniae. While most patients are being managed conservatively these
      days, nephrectomy may be needed in severe cases.

PMID- 29445495
TI  - Rituximab therapy for hepatitis C virus-associated cryoglobulinemic
      membranoproliferative glomerulonephritis.
AB  - Membranoproliferative glomerulonephritis associated with mixed cryoglobulinemia
      is the most common form of kidney disease observed in relation to hepatitis C
      virus (HCV) infection. Rituximab, a monoclonal antibody against CD20, is an
      effective treatment for severe and/or refractory HCV-related vasculitis and may
      evade the need for dialysis as in our patient.

PMID- 29445496
TI  - Giant genital warts.
AB  - Genital warts are quite common and should be treated early with nonaggressive
      conservative or invasive methods. When they are severely neglected patients may
      be submitted to amputative surgical management. Preoperatively malignant
      transformation of the tumors cannot be excluded.

PMID- 29445497
TI  - Transgastric decompression using a newly developed nasojejunal tube in a
      postgastrostomy patient with adhesive small bowel obstruction.
AB  - For postgastrostomy patients suffering from adhesive small bowel obstruction,
      transgastric decompression with a multiluminal nasojejunal tube is an effective
      and more comfortable alternative to conventional nasal tubing using an ileus
      tube.

PMID- 29445498
TI  - Widespread finger skin metastases of melanoma.
AB  - Metastatic melanoma is a fatal disease with a rapid systemic dissemination.
      Almost every organ might be affected, but lungs, liver, bone, brain, and skin are
      the most frequently involved sites. Intravascular microtumoral embolism is
      believed to account for the distant cutaneous metastases that might be the first
      manifestation of disease progression in most of the cases.

PMID- 29445499
TI  - Clinical presentation and imaging of a rare case of Tarsal Tuberculosis.
AB  - A 43-year-old woman arrived to emergency unit of our hospital, referring intense
      deteriorated pain and swelling of midfoot. Rapid clinical evolvement of
      osteoarticular tuberculosis represents a potential clinical scenario. Clinicians
      should always include foot tuberculosis in differential diagnosis, in cases of
      severe clinical and radiological manifestations.

PMID- 29445500
TI  - Endovascular clot retrieval in extensive cerebral venous sinus thrombosis (CVST):
      a videographic report.
AB  - Urgent anticoagulation, despite the presence of acute cerebral hematoma, improves
      survival as well as the prognosis. Surgical decompression is a life-saving
      procedure and is required in a selected group of patients with considerable mass
      effect and elevated intracranial pressure (ICP). Endovascular thrombectomy is a
      novel approach to reduce the clot burden, achieve venous patency, and reduce ICP.

PMID- 29445501
TI  - Saphenous nerve block as a diagnosis tool for chronic postsurgical pain of the
      left medial calf.
AB  - Ultrasound-guided saphenous nerve block above the knee may be a valuable
      diagnosis tool in patient presenting chronic pain of the calf.

PMID- 29445502
TI  - Long-term recovery following critical illness in an Australian cohort.
AB  - Background: Almost all data on 5-year outcomes for critical care survivors come
      from North America and Europe. The aim of this study was to investigate long-term
      mortality, physical function, psychological outcomes and health-related quality
      of life in a mixed intensive care unit cohort in Australia. Methods: This
      longitudinal study evaluated 4- to 5-year outcomes. Physical function (six-minute
      walk test) and health-related quality of life (Short Form 36 Version 2) were
      compared to 1-year outcomes and population norms. New psychological data (Center
      for Epidemiological Studies-Depression, Impact of Events Scale) was collected at
      follow-up. Results: Of the 150 participants, 66 (44%) patients were deceased by
      follow-up. Fifty-six survivors were included with a mean (SD) age of 64 (14.2).
      Survivors' mean (SD) six-minute walk distance increased between 1 and 4 to 5
      years (465.8 m (148.9) vs. 507.5 m (118.2)) (mean difference = - 24.5 m, CI -
      58.3, 9.2, p = 0.15). Depressive symptoms were low: median (IQR) score of 7.0
      (1.0-15.0). The mean level of post-traumatic stress symptoms was low-median (IQR)
      score of 1.0 (0-11.0)-with only 9 (16%) above the threshold for potentially
      disordered symptoms. Short-Form 36 Physical and Mental Component Scores did not
      change between 1 and 4 to 5 years (46.4 (7.9) vs. 46.7 (8.1) and 48.8 (13) vs.
      48.8 (11.1)) and were within a standard deviation of normal. Conclusions:
      Outcomes of critical illness are not uniform across nations. Mortality was
      increased in this cohort; however, survivors achieved a high level of recovery
      for physical function and health-related quality of life with low psychological
      morbidity at follow-up. Trial registration: The trial was registered with the
      Australian New Zealand Clinical Trials Registry ACTRN12605000776606.

PMID- 29445503
TI  - Overview of occupational cancer in painters in Korea.
AB  - Comprehensive consideration is necessary for setting guidelines to evaluate
      evidence of occupational cancer in painters due to work-related exposure to
      carcinogens in paint (a phenomenon termed herein as "work-relatedness"). The aim
      of the present research is to perform a comprehensive review and to suggest
      criteria for the provision of compensation for occupational neoplasm among
      painters in Korea. In order to perform a comprehensive review, this study
      assessed and evaluated scientific reports of carcinogenicities from the
      International Agency for Research on Cancer (IARC) and the Industrial Injuries
      Advisory Council (IIAC), as well as reviewed the existing literature about
      occupational exposure among painters in Korea and the epidemiologic
      investigations of claimed cases of cancer among painters in Korea. The IARC
      declares that occupational exposures in commercial painting are classified as
      Group 1 carcinogens for lung cancer and bladder cancer among painters. The
      epidemiologic studies show consistent causal relationships between occupational
      exposure in painters and cancers such as lung cancer [meta relative risk: 1.34
      (95% confidence intervals (CIs): 1.23-1.41)] and bladder cancer [meta relative
      risk: 1.24 (95% CIs: 1.16-1.33)]. In reviewing occupational cancer risks for
      commercial painters, the Industrial Injuries Advisory Council (IIAC) confirms
      occupational cancer risks for lung and bladder cancer among commercial painters.
      According to the IIAC, however, the elevated cancer risks reported in existing
      literature are not doubled in either lung or bladder cancer in commercial
      painters relative to the risks of these cancers in the general population. Based
      on our review of existing Korean articles on the topic, painters are exposed to
      potential carcinogens including polycyclic aromatic hydrocarbons (PAHs), benzene,
      hexavalent chrome, crystalized silica, asbestos, and other agents, and relative
      levels are estimated within commercial painting processes. However, the cancer
      risks of occupational exposure to Group 1 carcinogens for lung and bladder cancer
      in painters per se are not fully assessed in existing Korean articles. Total work
      duration, potential carcinogens in paint, mixed exposure to paints across various
      industries such as construction and shipbuilding, exposure periods, latent
      periods, and other factors should be considered on an individual basis in
      investigating the work-relatedness of certain types of cancer in commercial
      painters.

PMID- 29445504
TI  - The relationship between night work and breast cancer.
AB  - Background: Since the International Agency for Research on Cancer classified
      shift work that involves circadian disruption as "probably carcinogenic to
      humans," there has been growing concern on the relationship between night work
      and breast cancer. In Korea, about 10-15% of workers are engaged in night-shift
      work, and breast cancer is one of the most common cancers in women. The purpose
      of this study was to review epidemiologic evidence on the relationship between
      night work and breast cancer. Methods: We reviewed 21 original articles and 5
      meta analyses on relationship between nightwork and breast cancer, and
      investigated the compensation criteria of Denmark. Results: The association
      between breast cancer and night work has been reported by numerous epidemiologic
      studies, including cohort studies, case-control studies, and meta-analysis.
      However, a dose-response relationship has not clearly emerged among workers
      exposed to less than 20 years of night work. Conclusion: Although there are some
      limitations to the epidemiological studies so far, further consideration of
      breast cancer cases in patients with high exposure to night work is needed to
      assess breast cancer as a work-related disease.

PMID- 29445506
TI  - Ulinastatin did not reduce mortality in elderly multiple organ failure patients:
      a retrospective observational study in a single center ICU.
AB  - Aim: Our aim was to evaluate the effect of ulinastatin on 28-day mortality in
      patients who developed multiple organ failure (MOF) related to their acute
      illness and were admitted to the intensive care unit (ICU). Methods: We carried
      out a retrospective observational study of MOF patients in a general ICU of a
      tertiary care hospital in Japan from January 2009 to December 2012. The primary
      outcome was 28-day all-cause mortality. Secondary outcomes were ventilator-free
      days, ICU-free days, and vasopressor-free days at day 28. We investigated the
      association between ulinastatin treatment and outcomes using multivariable
      regression analysis. Results: A total of 212 MOF patients were included, 79 (37%)
      of whom received ulinastatin. The median age was 70 years (interquartile range,
      60-77) and median APACHE II score was 25 (interquartile range, 19-29). Overall 28
      day mortality was 20%. There were no significant differences between the
      ulinastatin group and the control group in age, gender, or APACHE II score. The
      ulinastatin group had higher prevalence of sepsis (44% versus 22%, P = 0.001).
      Multivariable logistic regression analysis showed that ulinastatin was not
      associated with 28-day mortality (odds ratio = 1.22; 95% confidence interval,
      0.54-2.79). Moreover, ulinastatin did not reduce the mortality in patients with
      sepsis (odds ratio = 1.92; 95% confidence interval, 0.52-7.13). However, ICU-free
      days and ventilator-free days was significantly fewer in the ulinastatin group
      than control group. Conclusions: In this retrospective observational study,
      ulinastatin was not associated with mortality in elderly patients with
      established MOF, although it might be related to patient's utility.

PMID- 29445507
TI  - Development of the Japanese version of the Cornell Assessment of Pediatric
      Delirium.
AB  - Aim: Delirium is a form of acute cerebral dysfunction and is associated with
      increased length of hospital stay, mortality, and health-care costs for adult
      patients in intensive care. However, in Japan, there are currently no reliable
      criteria or tools for diagnosing delirium in critically ill pediatric patients.
      The purpose of this study was to translate the Cornell Assessment of Pediatric
      Delirium (CAPD)-a screening tool for pediatric delirium-from English to Japanese
      for use in the diagnosis of delirium for pediatric patients in pediatric
      intensive care units. Methods: The back-translation method was used to ensure
      equivalence in the Japanese version of the CAPD and its accompanying
      developmental anchor points. The translation process was repeated by a
      multidisciplinary committee of medical researchers and clinicians. Results: The
      final back-translated version of the CAPD was submitted to the original author,
      who gave her approval. Conclusion: The Japanese CAPD was developed and its
      effectiveness tested using a standardized procedure. Further study is required to
      test the validity and reliability of the Japanese version of the CAPD.

PMID- 29445508
TI  - Development of the Japanese version of the Preschool Confusion Assessment Method
      for the ICU.
AB  - Aim: Delirium is associated with various negative clinical outcomes, such as
      decline in cognitive ability, increased length of hospital stay, and higher
      mortality. For these reasons, early diagnosis of delirium is critical.
      Unfortunately, there are no reliable diagnostic criteria or tool of delirium for
      infants and preschool-aged children in Japan. : The aim of the present study was
      to translate a new delirium assessment tool, the Preschool Confusion Assessment
      Method for the Intensive Care Unit (psCAM-ICU), for accurately diagnosing
      clinically ill infants and preschool-aged children, from English to Japanese.
      Methods: The translation was undertaken with the internationally established back
      translation method. The translation was repeated blindly and independently by
      eight medical researchers and clinicians from multiple disciplines. Any
      discrepancy evident from the translated works was discussed and resolved.
      Results: We report the successful development of the Japanese version of psCAM
      ICU. However, before its full application, this diagnostic tool requires further
      testing and study, most notably for its validation and reliability. Conclusion: A
      Japanese version of the psCAM-ICU was developed.

PMID- 29445509
TI  - A case of paraplegia that developed 6 years after thoracic endovascular aortic
      repair for blunt traumatic aortic injury.
AB  - Case: Thoracic endovascular aortic repair (TEVAR) is becoming the standard
      therapy for blunt thoracic aortic injury (BTAI). However, the long-term outcomes
      of TEVAR for BTAI remain unclear. A 36-year-old man was admitted to our emergency
      department with dyspnea. He had been involved in a serious traffic accident 6
      years earlier, requiring TEVAR for BTAI. Outcome: Acute heart failure and
      pneumonia were diagnosed on this admission. His respiratory condition improved,
      but paraplegia developed 10 h after hospitalization. Magnetic resonance imaging
      showed an intraspinal longitudinal area of signal hyperintensity, and spinal cord
      infarction was diagnosed. Conclusion: Although the causal relationship between
      the TEVAR and spinal cord infarction remains unclear, paraplegia as a long-term
      complication after TEVAR does not appear to have been reported previously, and so
      represents a potentially important complication.

PMID- 29445510
TI  - A neurologist and ataxia: using eye movements to learn about the cerebellum.
AB  - The cerebellum, its normal functions and its diseases, and especially its
      relation to the control of eye movements, has been at the heart of my academic
      career. Here I review how this came about, with an emphasis on epiphanies,
      "tipping points" and the influences of mentors, colleagues and trainees. I set a
      path for young academicians, both clinicians and basic scientists, with some
      guidelines for developing a productive and rewarding career in neuroscience.

PMID- 29445511
TI  - Management of group b streptococcus-positive pregnant women at maternity homes in
      JAPAN: a questionnaire survey of compliance among midwives.
AB  - Background: Per the 2014 Japanese Midwives Association (JMA) guidelines, midwives
      were allowed to manage the deliveries for group B streptococcus (GBS)-positive
      pregnant women in labour at maternity homes without the supervision of a medical
      doctor if they complied with the guidelines of the Japan Society of Obstetrics
      and Gynecology (JSOG), wherein midwives working for maternity homes are expected
      to cooperate with commissioned obstetricians and paediatricians in cooperative
      medical facilities. We examined the rate of compliance with these JMA and JSOG
      guidelines regarding the management of GBS-positive pregnant women among midwives
      at maternity homes in Japan. Methods: Between October and December 2015, an
      anonymous questionnaire was distributed to 337 maternity homes registered with
      the JMA by mail. The questionnaire obtained information regarding the timing of
      GBS screening, specimen collection, transfer of GBS-positive pregnant women from
      a maternity home to a hospital, administration of intrapartum antibiotic
      prophylaxis, and collaboration between midwives and commissioned obstetricians.
      Data were analysed using descriptive statistics. We used frequency distribution
      as the statistical test. Results: Responses were received from 246 (73.0%)
      maternity homes, of which complete responses from 204 maternity homes (valid
      response rate, 60.5%) were analysed. Of these 204 maternity homes, only 97
      (47.5%) conducted a GBS screening test during 33-37 weeks of gestation as
      recommended by the JSOG guidelines. Although midwives alone managed GBS-positive
      pregnant women in labour at 135 maternity homes (66.2%), intrapartum antibiotic
      prophylaxis, as recommended by the JSOG guidelines, was conducted in only 111
      (54.4%). Moreover, only 37.0% (50/135) and 82.2% (111/135) of maternity homes
      ensured that GBS-positive pregnant women in labour with an elapse of >=18 h after
      PROM and a body temperature of >=38.0  degrees C, respectively, were transferred
      to a hospital by ambulance. Only at 58.3% (119/204) of maternity homes did
      midwives discuss the management of labour for GBS-positive pregnant women with
      commissioned obstetricians. Conclusions: Some midwives working for maternity
      homes did not follow the JMA and JSOG guidelines of the management of GBS
      positive pregnant women. For improving compliance rates, midwives at maternity
      homes should discuss the management of GBS-positive pregnant women with
      commissioned doctors more carefully and concretely per the existing guidelines.

PMID- 29445512
TI  - Changes in tear volume and ocular symptoms of patients receiving oral anticancer
      drug S-1.
AB  - Background: Most eye disorders are not fatal but may deteriorate the quality of
      life of a patient. The eye disorder that is most frequently reported in the
      cancer chemotherapy is associated with the combination of
      tegafur/gimeracil/potassium oxonate (S-1). However, preventive methods or
      treatment methods for the eye disorder have not yet been established. This study
      aimed to determine changes in tear volume and subjective ocular symptoms during
      the treatment period in patients receiving S-1 monotherapy for early detection of
      adverse effects in the eye and establishment of its treatment methods. Methods:
      This study included eleven patients receiving S-1 monotherapy as a postoperative
      adjuvant chemotherapy for gastric cancer. Six subjective ocular symptoms
      including watering eyes were evaluated and changes in tear volume measured by the
      Schirmer's test in patients receiving S-1 during the treatment period. In the
      present study, the patients were divided into "no watering eyes" (patients not
      experienced watering eyes) group and "watering eyes" (patients experienced
      watering eyes even once) group. Results: Six out of eleven patients developed
      watering eyes after receiving S-1 monotherapy. Among these, the earliest onset
      occurred on the 2nd week after oral administration. Watering eyes and eye
      discharge were highly related in patients having a trouble in daily life due to
      the decreased QOL. Changes in tear volume in the "watering eyes" group
      significantly increased compared to the "no watering eyes" group during the
      treatment period, especially when the patients had no subjective symptom of the
      increased tear volume. Conclusions: It is essential to prevent eye disorders
      including watering eyes as an adverse effect of S-1 administration. The present
      study recommends that the tear volume should be periodically measured using
      Schirmer's test, and the patient should be interviewed regarding the subjective
      ocular symptoms for the early detection of watering eyes caused by S-1
      administration. If the tear volume can not be measured periodically, medical
      staffs should pay attention to the patient with eye discharge.

PMID- 29445513
TI  - Evaluating different interrow distance between corn and soybean for optimum
      growth, production and nutritive value of intercropped forages.
AB  - Background: Maize fodder is being used as staple feed for livestock but it lacks
      protein and essential amino acids; lysine and tryptophan. Intercropping maize
      with leguminous soybean crop is promising technique under limited land resources
      of South Korea but it can only give considerable advantages when adequate
      distance is provided between corn and soybean rows. Main aim of present study was
      to find-out adequate distance between corn and soybean seeding rows for optimum
      growth, yield and nutritive value of intercropped forage. Methods: Different
      interrow distances between corn and soybean were evaluated under four treatments,
      viz. 1) Corn sole as positive control treatment 2) Zero cm between corn and
      soybean (control); 2) Five cm between corn and soybean; 3) 10 cm between corn and
      soybean, with three replicates under randomized block design. Results: Findings
      depicted that height and number of corn stalks and ears were similar (P > 0.05)
      among different treatments. Numerically average corn ear height was decreased at
      zero cm distance. Dry matter percentage in all components; corn stalk, corn ear
      and soybean was also found not different (P > 0.05) but dry matter yield in
      component of corn ear was lower (P < 0.05) at zero cm distance as compared to
      that of 5 and 10 cm interrow distances. In case of nutritive value, total
      digestible nutrient yield in intercropped corn was also found lower (P < 0.05) at
      zero cm distance than that of 5 and 10 cm interrow distances between corn and
      soybean seeding rows. Substantial decrease in dry matter yield of maize ear at
      zero cm distance might be attributed to factor of closed interrow spacing which
      made interplant competition more intensified for light interception, necessary
      for photosynthetic activity. Lower dry matter yield in ear also reduced total
      digestible nutrients in intercropped maize because it was determining factor in
      calculation of digestible nutrients. The optimum yield and nutritive value of
      forage at wider interrow distance i.e. 5 cm between corn and soybean might be due
      to adequate interseed distance. Conclusion: Conclusively, pattern of corn and
      soybean seeding in rows at 5 cm distance was found suitable which provided
      adequate interrow distance to maintain enough mutual cooperation and decreased
      competition between both species for optimum production performance and nutritive
      value of intercropped forage.

PMID- 29445514
TI  - Exploring computerised cognitive training as a therapeutic intervention for
      people with Huntington's disease (CogTrainHD): protocol for a randomised
      feasibility study.
AB  - Background: Cognitive impairments, especially deficits of executive function,
      have been well documented as a core and early feature in Huntington's disease
      (HD). Cognitive impairments represent considerable burden and can be devastating
      for people and families affected by HD. Computerised cognitive training
      interventions that focus on improving executive function present a possible non
      pharmacological treatment option. We propose to determine the feasibility,
      acceptability, and appropriate outcome measures for use in a randomised
      controlled feasibility study. Methods/design: Participants will be randomised
      into either a computerised cognitive training group or a control group. Those
      randomised to the training group will be asked to complete a cognitive training
      intervention based on the HappyNeuron Pro software tasks of executive function,
      for a minimum of 30 min, three times a week for the 12-week study duration.
      Participants in the control group will not receive computerised cognitive
      training but will receive a similar degree of social interaction via equivalent
      study and home visits. We will explore quantitative outcome measures, including
      measures of cognitive performance, motor function, questionnaires and semi
      structured interviews, as well as magnetic resonance imaging (MRI) measures in a
      subset of participants. Feasibility will be determined through assessment of
      recruitment, retention, adherence and acceptability of the intervention.
      Discussion: The results of this study will provide crucial guidance and
      information regarding the feasibility of conducting a randomised controlled study
      into computerised cognitive training in HD. This study is crucial for the
      development of larger definitive randomised controlled trials which are powered
      to determine efficacy and for the development of future cognitive training
      programmes for people affected by HD. Trial registration: The study is registered
      on clinicaltrials.gov and has the unique identifier NCT02990676.

PMID- 29445515
TI  - Telementoring with project ECHO: a pilot study in Europe.
AB  - The Extension of Community Healthcare Outcomes (ECHO) project is a novel
      educational intervention designed in New Mexico to transfer subspecialty
      knowledge about hepatitis C virus (HCV) to primary care providers, thereby
      increasing patient access to HCV care. The ECHO model has been shown to deliver
      educational benefits and to result in good treatment outcomes for HCV-infected
      individuals in the USA; however, this approach has not been assessed in a
      European setting. We sought to evaluate the feasibility, acceptability and
      implementation of the ECHO model in Ireland using a pilot study. We present a
      descriptive review of recruitment, participation, retention and cost of the
      intervention as well as a qualitative review of the views of participants on the
      barriers, benefits and acceptability of the ECHO model. In the original Project
      ECHO in New Mexico, geographical distance posed the greatest barrier to accessing
      HCV care. In Ireland, people who inject drugs (PWID) were identified by
      interviewees as the main group facing barriers to accessing specialist HCV care.
      State-employed doctors and nurses caring for large numbers of HCV-infected PWID
      in opiate substitution treatment centres and homeless hostels were successfully
      recruited to participate in the project. Self-employed general practitioners did
      not participate, due mainly to a lack of time and the absence of reimbursement
      for participation. Practitioners who participated in the pilot reported benefits
      to themselves and their patients and would like to continue to participate in
      similar multidisciplinary, multisite educational interventions in the future.

PMID- 29445516
TI  - Does this treatment work for me? The patient's role in assessing medical care.
AB  - Randomised clinical trials are designed to determine whether a particular
      treatment is appropriate to make a significant difference to the health of a
      defined population and to aid its approval for use. For an accurate, cheap and
      simple assessment to see if a treatment benefits an individual person, all that
      is needed is a pen, paper, simple pocket calculator and daily recording of a few
      variables. It requires the ability to read and write and to understand addition
      and division. Factorial design of experiments is used to show the impact of
      several variables and their interaction on the person's health status. An example
      of a 75-year-old man with an enlarged prostate is used here to illustrate this
      approach. This person was able to understand and reduce side effects, lower the
      costs of medication by 83% and improve measured health status by 28%. A
      multivariate model for this person was then created with about 450 person-days of
      data.

PMID- 29445505
TI  - The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic
      Shock 2016 (J-SSCG 2016).
AB  - Background and Purpose: The Japanese Clinical Practice Guidelines for Management
      of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of
      clinical practice guidelines for sepsis and septic shock created jointly by the
      Japanese Society of Intensive Care Medicine and the Japanese Association for
      Acute Medicine, was first released in February 2017 in Japanese. An English
      language version of these guidelines was created based on the contents of the
      original Japanese-language version. Methods: Members of the Japanese Society of
      Intensive Care Medicine and the Japanese Association for Acute Medicine were
      selected and organized into 19 committee members and 52 working group members.
      The guidelines were prepared in accordance with the Medical Information Network
      Distribution Service (Minds) creation procedures. The Academic Guidelines
      Promotion Team was organized to oversee and provide academic support to the
      respective activities allocated to each Guideline Creation Team. To improve
      quality assurance and workflow transparency, a mutual peer review system was
      established, and discussions within each team were open to the public. Public
      comments were collected once after the initial formulation of a clinical question
      (CQ), and twice during the review of the final draft. Recommendations were
      determined to have been adopted after obtaining support from a two-thirds
      (>66.6%) majority vote of each of the 19 committee members. Results: A total of
      87 CQs were selected among 19 clinical areas, including pediatric topics and
      several other important areas not covered in the first edition of the Japanese
      guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in
      addition to ratings of the strengths of the recommendation and its supporting
      evidence were also added to each recommendation statement. We conducted meta
      analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an
      expert consensus due to insufficient evidence. No recommendations were provided
      for 5 CQs. Conclusions: Based on the evidence gathered, we were able to formulate
      Japanese-specific clinical practice guidelines that are tailored to the Japanese
      context in a highly transparent manner. These guidelines can easily be used not
      only by specialists, but also by non-specialists, general clinicians, nurses,
      pharmacists, clinical engineers, and other healthcare professionals.

PMID- 29445518
TI  - Why do endocrine profiles in elite athletes differ between sports?
AB  - Background: Endocrine profiles have been measured on blood samples obtained
      immediately post-competition from 693 elite athletes from 15 Olympic Sports
      competing at National or International level; four were subsequently excluded
      leaving 689 for the current analysis. Methods: Body composition was measured by
      bioimpedance in a sub-set of 234 (146 men and 88 women) and from these data a
      regression model was constructed that enabled 'estimated' lean body mass and fat
      mass to be calculated on all athletes. One way ANOVA was used to assess the
      differences in body composition and endocrine profiles between the sports and
      binary logistical regression to ascertain the characteristic of a given sport
      compared to the others. Results: The results confirmed many suppositions such as
      basketball players being tall, weightlifters short and cross-country skiers
      light. The hormone profiles were more surprising with remarkably low testosterone
      and free T3 (tri-iodothyronine) in male powerlifters and high oestradiol, SHBG
      (sex hormone binding globulin) and prolactin in male track and field athletes.
      Low testosterone concentrations were seen 25.4% of male elite competitors in 12
      of the 15 sports and high testosterone concentrations in 4.8% of female elite
      athletes in 3 of the 8 sports tested. Interpretation of the results is more
      difficult; some of the differences between sports are at least partially due to
      differences in age of the athletes but the apparent differences between sports
      remain significant after adjusting for age. The prevalence of 'hyperandrogenism'
      (as defined by the IAAF (International Association of Athletics Federations) and
      IOC (International Olympic Committee)) amongst this cohort of 231 elite female
      athletes was the highest so far recorded and the very high prevalence of
      'hypoandrogenism' in elite male athletes a new finding. Conclusions: It is
      unclear whether the differences in hormone profiles between sports is a reason
      why they become elite athletes in that sport or is a consequence of the arduous
      processes involved. For components of body composition we know that most have a
      major genetic component and this may well be true for endocrine profiles.

PMID- 29445517
TI  - Autonomic components of Complex Regional Pain Syndrome (CRPS) are favourably
      affected by Electrical Twitch-Obtaining Intramuscular Stimulation (ETOIMS):
      effects on blood pressure and heart rate.
AB  - Introduction: Favourable pain relief results on evoking autonomous twitches at
      myofascial trigger points with Electrical Twitch Obtaining Intramuscular
      Stimulation (ETOIMS). Aim: To document autonomic nervous system (ANS) dysfunction
      in Complex Regional Pain Syndrome (CRPS) from blood pressure (BP) and pulse/heart
      rate changes with ETOIMS. Methods and materials: A patient with persistent pain
      regularly received serial ETOIMS sessions of 60, 90, 120 or >=150 min over 24
      months. Outcome measures include BP: systolic, diastolic, pulse pressure and
      pulse/heart rate, pre-session/immediate-post-session summed differences (SDPPP
      index), and pain reduction. His results were compared with that of two other
      patients and one normal control. Each individual represented the following
      maximal elicitable twitch forces (TWF) graded 1-5: maximum TWF2: control subject;
      maximum TWF3: CRPS patient with suspected ANS dysfunction; and maximum TWF4 and
      TWF5: two patients with respective slow-fatigue and fast-fatigue twitches who
      during ETOIMS had autonomous twitching at local and remote myotomes
      simultaneously from denervation supersensitivity. ETOIMS results between TWFs
      were compared using one-way analysis of variance test. Results: The patients
      showed immediate significant pain reduction, BP and pulse/heart rate
      changes/reduction(s) except for diastolic BP in the TWF5 patient. TWF2 control
      subject had diastolic BP reduction with ETOIMS but not with rest. Linear
      regression showed TWF grade to be the most significant variable in pain
      reduction, more so than the number of treatments, session duration and treatment
      interval. TWF grade was the most important variable in significantly reducing
      outcome measures, especially pulse/heart rate. Unlike others, the TWF3 patient
      had distinctive reductions in SDPPP index. Conclusions: Measuring BP and
      pulse/heart rate is clinically practical for alerting ANS dysfunction maintained
      CRPS. SDPPP index (>=26) and pulse/heart rate (>=8) reductions with almost every
      ETOIMS treatment, plus inability to evoke autonomous twitches due to pain-induced
      muscle hypertonicity, are pathognomonic of this problem.

PMID- 29445519
TI  - Highly efficient generation of knock-in transgenic medaka by CRISPR/Cas9-mediated
      genome engineering.
AB  - Background: Medaka (Oryzias latipes) is a popular animal model used in vertebrate
      genetic analysis. Recently, an efficient (~ 30%) knock-in system via non
      homologous end joining (NHEJ) was established in zebrafish using the CRISPR/Cas9
      system. If the same technique were applicable in medaka, it would greatly expand
      the usefulness of this model organism. The question of the applicability of
      CRISPR/Cas9 in medaka, however, has yet to be addressed. Results: We report the
      highly efficient generation of knock-in transgenic medaka via non-homologous end
      joining (NHEJ). Donor plasmid containing a heat-shock promoter and a reporter
      gene was co-injected with a short guide RNA (sgRNA) targeted for genome
      digestion, an sgRNA targeted for donor plasmid digestion, and Cas9 mRNA. Broad
      transgene expression in the expression domain of a target gene was observed in
      approximately 25% of injected embryos. By raising these animals, we established
      stable knock-in transgenic fish with several different constructs for five
      genetic loci, obtaining transgenic founders at efficiencies of > 50% for all five
      loci. Further, we show that the method is useful for obtaining mutant alleles. In
      the experiments where transgene integrations were targeted between the
      transcription start site and the initiation methionine, the resultant transgenic
      fish became mutant alleles. Conclusion: With its simplicity, design flexibility,
      and high efficiency, we propose that CRISPR/Cas9-mediated knock-in via NHEJ will
      become a standard method for the generation of transgenic and mutant medaka.

PMID- 29445520
TI  - Efficacy and safety of azilsartan medoxomil, an angiotensin receptor blocker, in
      Korean patients with essential hypertension.
AB  - Background: This was a phase 3, randomized, double-blind, placebo-controlled
      study. Methods: Adult Korean patients with essential hypertension and a baseline
      mean sitting clinic systolic blood pressure (scSBP) >=150 and <=180 mmHg were
      randomized to 6-week treatment with placebo (n = 65), azilsartan medoxomil (AZL
      M) 40 mg (n = 132), or AZL-M 80 mg (n = 131). The primary endpoint was the change
      from baseline to week 6 in trough scSBP. Results: The least-squares mean
      (standard error) change from baseline in trough scSBP in the placebo, AZL-M 40
      mg, and 80-mg groups at week 6 were - 8.8 (2.00), - 22.1 (1.41), and - 23.7
      (1.40) mmHg, respectively (p < 0.001 for AZL-M 40 and 80 mg vs placebo). No
      clinically meaningful heterogeneity in efficacy was observed between subgroups
      (age, sex, diabetes status) and the overall population. Treatments were well
      tolerated and adverse events were similar between groups. Conclusions: Results of
      this study confirm a positive benefit-risk profile of AZL-M for essential
      hypertension in Korean adults. Trial registration: Clinicaltrial.gov; identifier
      number: NCT02203916. Registered July 28, 2014 (retrospectively registered).

PMID- 29445521
TI  - A method for co-creation of an evidence-based patient workbook to address alcohol
      use when quitting smoking in primary care: a case study.
AB  - Plain English summary: The purpose of this paper is to describe a patient
      engagement event designed to create an educational workbook with smokers who
      drink alcohol at harmful levels. The goal was to create a workbook that combined
      scientific evidence with patients' values, preferences, and needs. Fourteen adult
      smokers who drink alcohol were invited to the Centre for Addiction and Mental
      Health (CAMH) to take part in a four-hour event to help design the workbook with
      the CAMH research team. Participants provided their opinions and ideas to create
      an outline for the workbook, including activities, images, and titles. The
      workbook - called Self-Awareness - is currently being offered in a smoking
      cessation program in 221 primary care clinics across Ontario to help smokers quit
      or reduce their harmful alcohol use. The patient engagement event was a useful
      way to co-create educational materials that incorporate both scientific research
      and patient needs. Abstract: Background Evidence-based medicine is the
      integration of best research evidence with clinical expertise and patient values.
      There are few methodologies on how to design evidence-based programs and
      resources to include patient values. The latter is an important aspect of patient
      centered care, and is essential for patients to trust the recommendations and
      empower them as consumers to make informed choices. This manuscript describes a
      participatory research approach to design patient-facing educational materials
      that incorporate both evidence-based and community-sensitive principles. These
      materials are intended to support smokers to reduce or stop harmful alcohol
      consumption. Methods Adult smokers who report consuming alcohol were invited to a
      co-creation meeting at the Centre for Addiction and Mental Health's Nicotine
      Dependence Service to guide the adaptation of evidence-based materials. The four
      hour event consisted of individual reflections, group discussions, and consensus
      building interactions. Detailed notes were taken and then incorporated into the
      material. Results Fourteen individuals participated in the event. The end product
      was a descriptive outline of an educational resource - entitled Self-Awareness -
      incorporating material from evidence-based workbooks and patient-driven features.
      Participants collaboratively selected the resource's content, structure, and
      titles. Conclusions This model describes a participatory research method that
      emphasizes the value of the patient perspective; preliminary evidence finds this
      adaptation approach can increase the adoption of resources. The process described
      in this article could be replicated in other settings to co-create evidence-based
      resources, interventions, and programs that reflect the needs of the community.
      Trial registration ClinicalTrials.gov NCT03108144. Retrospectively registered 11
      April 2017.

PMID- 29445522
TI  - Early changes in macular optical coherence tomography parameters after
      Ranibizumab intravitreal injection in patients with exsudative age-related
      macular degeneration.
AB  - Background: Evaluation of the impact of different macular optical coherence
      parameters on visual acuity as early as 1 day after injection of ranibizumab in
      patients with subfoveal exsudative age-related macular degeneration. Methods:
      This was an interventional, non randomized, open label prospective study, where
      we evaluated 20 eyes of 20 patients affected by exudative age-related macular
      degeneration. These patients were treated with injections of ranibizumab between
      February 2013 and January 2015. The primary endpoint of this study was to
      evaluate the early changes in optical coherence tomography parameters (retinal
      thickness, central and total retinal volume) and impact on best-corrected visual
      acuity (BCVA) obtained by logarithm of minimum resolution using ETDRS protocol in
      patients treated with a single dose intravitreal injection of ranibizumab (0.5
      mg/0.05 mL) during the first month of follow. The patients were evaluated on the
      first day, them at 7 and 30 days after the treatment. The National Eye Institute
      Visual Functioning Questionnaire was applied during the study period to assess
      early perception of ranibizumab injection effectiveness. The adverse events were
      monitored throughout the study. Results: Central retinal thickness values at 1
      (464.0 +/- 97.8 um), 7 (379.9 +/- 107.8 um) and 30 days (365.5 +/- 95.1 um) after
      ranibizumab injection showed a statically significant reduction when compared
      with baseline results (P = 0.01, P = 0.001, P = 0.001, respectively). Similar
      alterations were observed in central and total retinal volume, which were
      detected early on the first day of evaluation, after the measurement at baseline
      (central: 0.36 +/- 0.07 vs. 0.40 +/- 0.10 mm3, P = 0.01; total: 9.62 +/- 1.10 vs.
      9.99 +/- 2.56 mm3, P = 0.002) and remained steady at 7 (P = 0.001, P = 0.002,
      respectively) and 30 days (P = 0.001, P = 0.004, respectively) with slight
      variations without losing their gains in these parameters. The best-corrected
      logarithm of minimum angle of resolution (logMAR) showed a statistically
      significant difference when compared to the baseline. (0.81 +/- 0.16 vs. 0.67 +/-
      0.24, P = 0.005). The NEI-VFQ-25 questionnaire demonstrate statically significant
      results after treatment. When patients were asked about the subjective
      improvement in visual quality, over 80% reported early improvement. Throughout
      the period of follow-up visits, no serious adverse events were reported.
      Conclusion: Intravitreal injection of ranibizumab can produce early changes in
      optical coherence tomography parameters and an improvement in perceived visual
      quality of patients with subfoveal exsudative age-related macular degeneration.

PMID- 29445523
TI  - Welcome to the 3rd Clinical Update Sleep at the Royal College of Physicians in
      London.

PMID- 29445525
TI  - Physiological consequences of CPAP therapy withdrawal in patients with
      obstructive sleep apnoea-an opportunity for an efficient experimental model.
AB  - Randomised controlled trials (RCTs) of continuous positive airway pressure (CPAP)
      in obstructive sleep apnoea (OSA) are time consuming, and their findings often
      inconclusive or limited due to suboptimal CPAP adherence in CPAP-naive patients
      with OSA. Short-term CPAP withdrawal in patients with prior optimal CPAP
      adherence results in recurrence of OSA and its consequences. Thus, this
      experimental model serves as an efficient tool to investigate both the
      consequences of untreated OSA, and potential treatment alternatives to CPAP. The
      CPAP withdrawal protocol has been thoroughly validated, and applied in several
      RCTs focusing on cardiovascular and metabolic consequences of untreated OSA, as
      well as the assessment of treatment alternatives to CPAP.

PMID- 29445524
TI  - Preface for the 3rd Clinical Update Sleep, 23rd February 2018, Royal College of
      Physicians, London, UK: year in review.

PMID- 29445526
TI  - Intermittent hypoxia, cardiovascular disease and obstructive sleep apnoea.
AB  - Obstructive sleep apnoea (OSA) is a common disorder and is associated with
      cardiovascular disease. Continuous positive airway pressure (CPAP), whilst
      reducing blood pressure, has not been shown to reduce cardiovascular events when
      used as a treatment solely for this purpose in patients with previous
      cardiovascular disease. Developing a better understanding of the mechanisms
      underlying cardiovascular disease in OSA is important to develop new treatments.
      Potential causative mechanisms for cardiovascular disease in OSA include arousal
      induced sympathetic activation, large intrathoracic pressure swings leading to
      shear stress on the heart and great vessels, and intermittent hypoxia (IH). This
      review discusses the role of IH, as a major physiological consequence of OSA, in
      the development of cardiovascular disease.

PMID- 29445527
TI  - Drug induced sleep endoscopy: its role in evaluation of the upper airway
      obstruction and patient selection for surgical and non-surgical treatment.
AB  - Sleep related breathing disorders cause obstruction of the upper airway which can
      be alleviated by continuous positive airway pressure (CPAP) therapy, oral devices
      or surgical intervention. Non-surgical treatment modalities are not always
      accepted by patients and in order to attain successful surgical outcomes,
      evaluation of the upper airway is necessary to carefully select the patients who
      would benefit from surgery. There are numerous techniques available to assess the
      upper airway obstruction and these include imaging, acoustic analysis, pressure
      transducer recording and endoscopic evaluation. It is essential to note that the
      nocturnal obstructive upper airway has limited muscle control compared to the
      tone of the upper airway lumen during wakefulness. Thus, if one were to attempt
      to identify the anatomical segments contributing to upper airway obstruction in
      sleep related breathing disorders; it must be borne in mind that evaluation of
      the airway must be performed if possible when the patient is awake and asleep
      albeit during drug induced sleep. This fact as such limits the use of imaging
      techniques for the purpose. Drug induced sleep endoscopy (DISE) was pioneered at
      Royal National Throat, Nose and Ear Hospital, London in 1990 and initially
      introduced as sleep nasendoscopy. The nomenclature and the technique has been
      modified by various Institutions but the core value of this evaluation technique
      remains similar and extremely useful for identifying the anatomical segment
      responsible for obstructing the upper airway during sleep in patients with sleep
      related breathing disorders. There have been numerous controversies that have
      surrounded this technique but over the last two decades most of these have been
      addressed and it now remains in the forefront of methods of evaluating the upper
      airway obstruction. A variety of sedative agents and different grading systems
      have been described and efforts to unify various aspects of the technique have
      been made. This article will look at its usefulness and advantages and will
      discuss some important contributions made to the field of evaluation of the upper
      airway using DISE.

PMID- 29445528
TI  - An update on mandibular advancement devices for the treatment of obstructive
      sleep apnoea hypopnoea syndrome.
AB  - Continuous positive airway pressure (CPAP) remains the gold standard treatment
      for obstructive sleep apnoea hypopnoea syndrome (OSAHS). However, the high
      efficacy of CPAP is offset by intolerance and poor compliance, which can
      undermine effectiveness. This means that alternatives to CPAP are also necessary.
      In recent years, oral appliances have emerged as the leading alternative to CPAP.
      There is now a strong body of evidence supporting their use in OSAHS and clinical
      guidelines now recommend their use in mild OSAHS and in more severe cases when
      CPAP fails. These devices are by no means a homogenous group as they differ
      greatly in both design and action. The most commonly used appliances are
      mandibular advancement devices (MAD) that increase airway diameter with soft
      tissue displacement achieved by mandibular protrusion. Despite the growing
      evidence, there are still barriers to MAD provision. Their effectiveness can be
      difficult to predict and there is debate about the required level of design
      sophistication. These uncertainties prevent more widespread inclusion of MAD
      within clinical sleep services. This review will focus on the efficacy,
      effectiveness, design features, side-effects of and patient selection for MAD
      therapy. Comparison will also be made between MAD and CPAP therapy.

PMID- 29445529
TI  - Cardiorespiratory interaction with continuous positive airway pressure.
AB  - The treatment of choice for obstructive sleep apnoea (OSA) is continuous positive
      airway pressure therapy (CPAP). Since its introduction in clinical practice, CPAP
      has been used in various clinical conditions with variable and heterogeneous
      outcomes. In addition to the well-known effects on the upper airway CPAP impacts
      on intrathoracic pressures, haemodynamics and blood pressure (BP) control.
      However, short- and long-term effects of CPAP therapy depend on multiple
      variables which include symptoms, underlying condition, pressure used, treatment
      acceptance, compliance and usage. CPAP can alter long-term cardiovascular risk in
      patients with cardiorespiratory conditions. Furthermore, the effect of CPAP on
      the awake patient differs from the effect on the patients while asleep, and this
      might contribute to discomfort and removal of the use interface. The purpose of
      this review is to highlight the physiological impact of CPAP on the
      cardiorespiratory system, including short-term benefits and long-term outcomes.

PMID- 29445531
TI  - Patient ventilator asynchrony and sleep disruption during non-invasive
      ventilation.
AB  - Patient-ventilator asynchrony (PVA) are a common phenomenon affecting all
      patients receiving long-term domiciliary ventilation. The interruption of
      synchrony between the patient and the ventilator has been reported to be a
      possible cause of nocturnal sleep disruption leaking to arousals, awakenings and
      reduced periods of stage 3 and REM sleep overnight. The cause of PVA is multi
      factorial driven frequently by leak at the interface, changing respiratory
      breathing patterns and changes in sleep stages. It currently remains unclear as
      to whether the PVA is the cause of sleep fragmentation or if PVA is purely a
      marker of unsuccessful ventilatory control, patient discomfort and underlying
      sleep disruption.

PMID- 29445530
TI  - Update: non-invasive ventilation in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) remains a common cause of morbidity
      and mortality worldwide. Patients with COPD and respiratory failure, whether
      acute or chronic have a poorer prognosis than patients without respiratory
      failure. Non-invasive ventilation (NIV) has been shown to be a useful tool in
      both the acute hospital and chronic home care setting. NIV has been well
      established as the gold standard therapy for acute decompensated respiratory
      failure complicating an acute exacerbation of COPD with reduced mortality and
      intubation rates compared to standard therapy. However, NIV has been increasingly
      used in other clinical situations such as for weaning from invasive ventilation
      and to palliate symptoms in patients not suitable for invasive ventilation. The
      equivocal evidence for the use of NIV in chronic hypercapnic respiratory failure
      complicating COPD has recently been challenged with data now supporting a role
      for therapy in selected subgroups of patients. Finally the review will discuss
      the emerging role of high flow humidified therapy to support or replace NIV in
      certain clinical situation.

PMID- 29445532
TI  - Sleep disordered breathing in motor neurone disease.
AB  - Motor neurone disease (MND) is a neurodegenerative disease defined by axonal loss
      and gliosis of upper and lower motor neurones in the motor cortex, lower
      brainstem nuclei and ventral horn of the spinal cord. MND is currently incurable
      and has a poor prognosis, with death typically occurring 3 to 5 years after
      disease onset. The disease is characterised by rapidly progressive weakness
      leading to paralysis, fasciculations, bulbar symptoms (including dysarthria and
      dysphagia) and respiratory compromise. Respiratory complications arise as a
      result of weakness of upper airway (pharyngeal and laryngeal) muscles and
      respiratory muscles (diaphragm, intercostal and accessory muscles) leading to
      respiratory failure. Due to early involvement of respiratory muscles in MND,
      sleep disordered breathing (SDB) occurs at a higher frequency than compared to
      the general population. SDB usually precedes daytime respiratory symptoms and
      chronic respiratory failure. It significantly impacts upon patients' quality of
      life and survival and its presence may predict prognosis. Managing SDB in MND
      with non-invasive ventilation (NIV) improves quality of life and survival. Early
      identification and management of SDB in MND patients is therefore crucial. This
      update will review assessments of respiratory muscle function, types of SDB and
      the effects of NIV in patients with MND.

PMID- 29445533
TI  - Insomnia and cognitive behavioural therapy-how to assess your patient and why it
      should be a standard part of care.
AB  - Hippocrates recognized the importance of asking about sleep as long ago as 400 BC
      when he wrote "sleep and watchfulness, both of them when immoderate, constitute
      disease". Disrupted sleep for any reason has immediate and long term consequences
      on physical and mental health. Insomnia disorder ("immoderate watchfulness")
      remains the commonest sleep disorder in primary and secondary care with an
      estimated 5-10% of the adult population affected. While it is commonly comorbid
      with other physical and mental health problems, the new diagnostic classification
      has been helpfully simplified such that it is considered a disorder in itself. If
      it is the patient's main concern, it warrants treatment. Patients and health
      professionals have often had limited teaching about effective strategies for
      insomnia which leaves many untreated and insomnia can be unfairly perceived as a
      challenging symptom to manage. The first line treatment is now well established
      as insomnia-specific cognitive behavioural therapy (CBTi) in the most recent US
      and European treatment guidelines. Over 25 years of high quality research have
      shown evidence for sustained improvements in sleep in those with insomnia alone
      or insomnia comorbid with other conditions. This is a simple CBT to deliver with
      better and safer outcomes than prescription hypnotics. Therefore, this review
      will cover the initial assessment of insomnia, including insomnia mimics, the
      selection of patients for treatment and the key components of CBT therapy.
      Finally, the review will cover evidence for different modes of delivery (online,
      self, help, group or individual face to face) in a variety of clinical settings.

PMID- 29445534
TI  - Delayed sleep-wake phase disorder.
AB  - Delayed sleep-wake phase disorder (DSWPD) is the most commonly encountered of the
      circadian rhythm sleep-wake disorders (CRSDs), and is often confused with sleep
      initiation insomnia. It typically emerges in teenage years and persists into
      adulthood. In essence, people with the disorder have an abnormally delayed major
      sleep episode relative to the dark phase of the solar cycle, and hence great
      difficulty initiating sleep at an appropriately early time, and, as a knock-on
      effect, waking at a desirable time in the morning, leading to chronic, and often
      quite severe sleep restriction trying to conform to a 9 to 5 schedule. As a
      result, sleep on free days is often extended in compensation. When released from
      such schedule constraints, sleep duration and quality is normal; it is just
      delayed. This review highlights elements of our current understanding of the
      epidemiology, associations and pathophysiology of the disorder, before discussing
      how some of our knowledge of sleep and circadian physiology can be applied to
      guide treatment of it.

PMID- 29445535
TI  - Clinical update on central hypersomnias.
AB  - The central hypersomnias encompass a range of conditions causing persisting or
      intermittent excessive daytime sleepiness (EDS). These conditions therefore
      present not infrequently in general clinical sleep practice, and remain in the
      differential for patients presenting with sleepiness. Our understanding of the
      pathophysiology, diagnosis and management of these conditions has progressed
      significantly over recent years, and in this article we review this group of
      disorders, focussing in particular on recent changes in classification and
      diagnosis, pathophysiological advances, and novel treatment options.

PMID- 29445536
TI  - Predictors of long-term adherence to continuous positive airway pressure in
      patients with obstructive sleep apnoea and acute coronary syndrome.
AB  - Background: Continuous positive airway pressure (CPAP) is an effective treatment
      for obstructive sleep apnoea (OSA), but an evaluation of CPAP adherence is rarely
      carried out among patients with acute coronary syndrome (ACS). The goals of the
      study are to analyse long-term adherence and identify the predictors of non
      compliance with CPAP treatment for patients with non-sleepy OSA and ACS. Methods:
      This is an ancillary study of the ISAACC study, which is a multicentre,
      prospective, open-label, parallel, randomized, and controlled trial (NCT01335087)
      in patients with hospital admission for ACS. For the purpose of this study, only
      non-sleepy patients with moderate or severe OSA and randomized to receive CPAP
      treatment were analysed (n=357). Non-compliance was defined as CPAP dropout or
      average cumulative CPAP use of <4 hours/night. Multivariable logistic regression
      analysis was performed to identify predictors of CPAP adherence. Results:
      Adherence to treatment was 35.3% at 12 months. According to the unadjusted
      analysis, higher apnoea-hypopnea index (AHI) (P<0.001) and oxygen desaturation
      index (ODI) (P=0.001) were associated with a lower risk of non-compliance.
      Multivariable logistic regression analysis showed that high AHI (P=0.0051), high
      amounts of smoking pack-year (P=0.0170), and long intensive care unit (ICU) stays
      (P=0.0263) were associated with lower odds of non-compliance. It also showed a
      significant interaction between ACS history and age (P=0.0131), such that young
      patients with their first ACS showed significantly lower odds of CPAP non
      compliance than patients with recurrent ACS and significantly lower odds of CPAP
      non-compliance were associated with ageing only in patients with recurrent ACS.
      Conclusions: Protective factors against non-compliance with CPAP treatment in non
      sleepy patients with ACS were illness severity (high values of AHI or ICU stay
      length) or smoking amount. Patients with no previous history of ACS showed lower
      odds of CPAP non-compliance than patients with a recurrent ACS with younger age.

PMID- 29445537
TI  - Neural respiratory drive and cardiac function in patients with obesity
      hypoventilation syndrome following initiation of non-invasive ventilation.
AB  - Background: Chronic hypercapnic respiratory failure (HRF) in obesity
      hypoventilation syndrome (OHS) is commonly treated using non-invasive ventilation
      (NIV). We hypothesised that treatment of OHS would improve neural respiratory
      drive index (NRDI) and cardiac function. Methods: Fourteen patients (8 females)
      with OHS, who were admitted for initiation of domiciliary NIV, were prospectively
      studied. Patients had (mean +/- SD): age (53+/-10 years), body mass index (BMI)
      (50.1+/-10.8 kg/m2), and pCO2 (7.3+/-0.9 kPa). NRDI was assessed by surface
      electromyogram of the parasternal intercostals. Cardiac function was assessed by
      transthoracic echocardiography (TTE). All measurements were performed at
      baseline, 6 weeks, and 3 months. Results: NRDI improved on day one following NIV
      set-up comparing to baseline (484.2+/-214.8 vs. 316.5+/-106.5 AU) and this
      improvement was maintained at 6 weeks (369.1+/-173.2 AU) and at 3 months (351.2+/
      167.1 AU) (P=0.004). No significant differences were identified in terms of
      cardiac function between baseline and 3 months [tricuspid annular plane systolic
      excursion (TAPSE) (24.6+/-5.8 vs. 23.0+/-4.0 mm, P=0.317); systolic pulmonary
      artery (PA) pressures (36.7+/-15.2 vs. 44.5+/-23.9 mmHg, P=0.163]. Conclusions:
      NIV improves NRDI in patients with OHS, while the cardiac function over a three
      month period remains unchanged.

PMID- 29445538
TI  - Peri-operative treatment of sleep-disordered breathing and outcomes in bariatric
      patients.
AB  - Background: Obstructive sleep apnoea (OSA) is increasingly common in bariatric
      patients undergoing sedation during elective surgery. However, it has not been
      established how significant a contributor it is to peri-operative respiratory
      complications and mortality. We sought to pre-operatively identify OSA in
      bariatric patients and record peri-operative complications during and after
      bariatric surgery. Methods: Data were collected and analysed from June 2014 to
      March 2017 for 410 bariatric surgery patients referred to the sleep laboratory
      for pre-operative screening and treatment of OSA. The STOP-Bang questionnaire,
      Epworth Sleepiness Scale (ESS) and nocturnal pulse oximetry were recorded and
      treatment was allocated with continuous positive airway pressure (CPAP). Peri
      operative complications and mortality were the primary outcome measures for
      patients receiving CPAP treatment for OSA, with patients who did not require CPAP
      used as control. The mean follow-up time for all patients was 433 and 732 days
      for the patients who had undergone bariatric surgery. The two groups were
      compared with Chi square test and unpaired two-tailed t-test. Results: OSA was
      present in any form in 70% of the screened patients; 40% of patients involved in
      the study received CPAP treatment. Patients receiving CPAP treatment [49.5 (11.3)
      years old, 61% female, 50.3 (8.5) kg/m2] were older, had a lower percentage of
      females and had a higher body mass index (BMI) than those not receiving CPAP
      [44.9 (12.0), 81% female, 46.6 (7.7)]. No significant differences were observed
      between patients on CPAP and those not on CPAP, there was no significant
      difference in hospital stay or rate of respiratory complications. Out of 53
      patients who had undergone bariatric surgery at the cut-off date, only 1 had
      suffered a respiratory complication. Conclusions: Bariatric patients who are
      screened pre-operatively for OSA and treated according to guidelines have no
      increased risk of respiratory complications compared to patients without OSA.

PMID- 29445539
TI  - The clinical usefulness of a self-administered questionnaire for sleep-disordered
      breathing in patients with neuromuscular disease.
AB  - Background: Patients with neuromuscular disease (NMD) are at risk of developing
      sleep-disordered breathing (SDB) with hypercapnic respiratory failure. We
      hypothesised that a self-administered questionnaire (SiNQ-5 scores) may be useful
      to assess patients who are established on treatment for NMD with SDB. Methods:
      Patients attending a tertiary referral centre filled in the SiNQ-5 (range 0-10
      points, lower scores indicating fewer symptoms). The questionnaire contains five
      questions related to breathlessness, sleep and posture. Patients with NMD and
      treated SDB were compared to NMD without SDB, to sleep apnoea, chronic
      obstructive pulmonary disease (COPD) and heart failure (HF) patients' scores, as
      well as a group of patients without SDB. Results were compared using Kruskal
      Wallis one-way analysis of variance, with Dunn/Bonferroni post-hoc tests if
      comparisons were found to be statistically significant. Results: A total of 265
      (156 male) patients completed the assessment, 40 had NMD with treated SDB [SiNQ-5
      score 3.4 (3.0) points], 11 had NMD without SDB [2.7 (2.9) points], 120 patients
      had obstructive sleep apnoea (OSA) [4.1 (2.6) points], 16 had COPD [3.9 (3.0)
      points] and 9 had HF [3.2 (2.8) points], 69 patients had other conditions with no
      evidence of SDB [3.0 (2.4) points; P=0.077]. Patients with NMD without SDB and
      those with SDB who were on treatment did not differ in their responses (P=0.417).
      Question #1 allowed discrimination between patients with NMD with SDB [0.8 (0.8)
      points] and other disorders without respiratory involvement [0.3 (0.6) points;
      P=0.024]. Conclusions: The SiNQ-5 scores in neuromuscular patients with SDB who
      are established on treatment and NMD patients without SDB, as well as in patients
      with other conditions leading to SDB are similar.

PMID- 29445540
TI  - The effect of positive and negative message framing on short term continuous
      positive airway pressure compliance in patients with obstructive sleep apnea.
AB  - Background: Continuous positive airway pressure (CPAP), the best available
      treatment for obstructive sleep apnea (OSA), requires long-term compliance to be
      effective. Behavioral interventions may be used to improve adherence to CPAP. We
      aimed to investigate whether positive or negative message framing impacts on CPAP
      compliance in patients with OSA, when compared to standard care. Methods:
      Consenting patients with confirmed OSA were randomly allocated to receive along
      with their CPAP either positively or negatively framed messages (Pos; Neg), or
      standard care (Con). Standardized motivational messages were read out to patients
      during an initial teaching session and through weekly telephone calls. Patients'
      compliance data were reviewed 2 and 6 weeks following CPAP initiation. Results:
      We randomized 112 patients to groups that were matched for age, BMI, and OSA
      severity. The positively framed group (Pos) showed greater CPAP usage after 2
      weeks (total use 53.7+/-31.4 hours) as compared to the negatively framed and the
      control group (35.6+/-27.4 and 40.8+/-33.5 hours, P<0.05); however, no
      differences were seen at 6 weeks. There were more dropouts in the control group
      than in either framed groups (Pos n=5; Neg n=8; Con n=11; P<0.05). Conclusions:
      Positively framed messages can improve CPAP adherence in patients with OSA in the
      short-term; however, strategies for implementing its long-term use need to be
      developed.

PMID- 29445541
TI  - Multiple dimensions of excessive daytime sleepiness.
AB  - Background: In this study we investigated subjective measures of sleepiness and
      related our findings to dimensions of affect, fatigue, emotion, mood and quality
      of life based on a hypothetical multidimensional model of sleepiness. Methods:
      Patients referred to a sleep clinic were assessed regarding their excessive
      daytime sleepiness (EDS), sleep complaints, routine and symptoms. Age, gender and
      body mass index (BMI), the Epworth Sleepiness Scale (ESS), the Stanford
      Sleepiness Scale (SSS), the Samn-Perelli fatigue Scale (SPS), the Global Vigor
      and Affect Scale (GVS and GAS, respectively), the Hospital Anxiety and Depression
      Scale (HADS-A and HADS-D, respectively), and the Positive and Negative Affect
      Schedule (PAS and NAS, respectively) scores were recorded. Results: Fifty
      patients [25 male, 45.2 (18.7) years] completed the questionnaires. The ESS
      scores were positively correlated with SSS, SPS, HADS-A, HADS-D and NAS scores
      and negatively with GVS and GAS scores (P<0.05). The SPS (P<0.001) and HADS-A
      scores (P=0.002) were independently associated with the ESS scores (R2=0.532,
      adjusted R2 =0.4794, P<0.001). Conclusions: A model of sleepiness that assesses
      dimensions of fatigue and anxiety could explain the symptom of subjective
      sleepiness better than the isolated use of the ESS.

PMID- 29445542
TI  - Assessing the sleeping habits of patients in a sleep disorder centre: a review of
      sleep diary accuracy.
AB  - Background: Excessive daytime sleepiness (EDS) is a complaint common to many
      aspects of medicine. There are primary and secondary causes for EDS, with
      secondary causes including a large number of common conditions. Primary causes,
      such as narcolepsy, are much rarer. When assessing for primary hypersomnia,
      restricted or fragmented sleep must be ruled out. This process involves
      assessment of sleeping habits using a sleep diary and/or actigraphy. Clinicians
      are suspicious of the accuracy with which patients use the former. This review
      aims to evaluate the accuracy of a sleep diary study against the 'objective gold
      standard' actigraphy report. Methods: Data from 35 patients at a Sleep Disorder
      Centre who underwent both a sleep diary and actigraphy study for suspected
      primary hypersomnia in 2016 was collected. Mean values of four variables were
      calculated: 'time of lights out', 'time to fall asleep', 'time of waking' and
      'sleep time'. The 'similarity' was assessed. This was a term defined in three
      different ways: if sleep diary values are accurate to within 20, 30 and 60 min
      respectively. Percentage 'similarity', mean time differences and standard
      deviations (SDs) were calculated for each variable. A paired t-test was also
      performed to assess the significance of the time differences between the two
      modalities. Results: Least accurate was 'sleep time', with 14.7%, 23.5% and 58.8%
      of patients within 20, 30 and 60 min of the actigraphy respectively. Mean time
      difference for this variable was 66 min (versus 33, 15 and 22). 'Time to fall
      asleep' was most accurate, with 76.5%, 82.4% and 100% 'similarity' respectively.
      Conclusions: The clinically acceptable accuracy has no universal definition, so
      clinicians must use experience and reasoning to determine this level to interpret
      this data. The review suggests that some variables are entered with high
      accuracy, and the diary is low cost and adds subjective information that cannot
      be gathered from actigraphy. Therefore, use is recommended to continue alongside
      actigraphy.

PMID- 29445543
TI  - Models for Preterm Cortical Development Using Non Invasive Clinical EEG.
AB  - The objective of this study was to evaluate the piglet and the mouse as model
      systems for preterm cortical development. According to the clinical context, we
      used non invasive EEG recordings. As a prerequisite, we developed miniaturized
      Ag/AgCl electrodes for full band EEG recordings in mice and verified that
      Urethane had no effect on EEG band power. Since mice are born with a "preterm"
      brain, we evaluated three age groups: P0/P1, P3/P4 and P13/P14. Our aim was to
      identify EEG patterns in the somatosensory cortex which are distinguishable
      between developmental stages and represent a physiologic brain development. In
      mice, we were able to find clear differences between age groups with a simple
      power analysis of EEG bands and also for phase locking and power spectral
      density. Interhemispheric coherence between corresponding regions can only be
      seen in two week old mice. The canolty maps for piglets as well as for mice show
      a clear PAC (phase amplitude coupling) pattern during development. From our data
      it can be concluded that analytic tools relying on network activity, as for
      example PAC (phase amplitude coupling) are best suited to extract basic EEG
      patterns of cortical development across species.

PMID- 29445544
TI  - Telomeric G-Quadruplexes: From Human to Tetrahymena Repeats.
AB  - The human telomeric and protozoal telomeric sequences differ only in one purine
      base in their repeats; TTAGGG in telomeric sequences; and TTGGGG in protozoal
      sequences. In this study, the relationship between G-quadruplexes formed from
      these repeats and their derivatives is analyzed and compared. The human telomeric
      DNA sequence G3(T2AG3)3 and related sequences in which each adenine base has been
      systematically replaced by a guanine were investigated; the result is Tetrahymena
      repeats. The substitution does not affect the formation of G-quadruplexes but may
      cause differences in topology. The results also show that the stability of the
      substituted derivatives increased in sequences with greater number of
      substitutions. In addition, most of the sequences containing imperfections in
      repeats which were analyzed in this study also occur in human and Tetrahymena
      genomes. Generally, the presence of G-quadruplex structures in any organism is a
      source of limitations during the life cycle. Therefore, a fuller understanding of
      the influence of base substitution on the structural variability of G
      quadruplexes would be of considerable scientific value.

PMID- 29445545
TI  - HIV-Stigma in Nigeria: Review of Research Studies, Policies, and Programmes.
AB  - Nigeria has about 3.8 million people living with HIV, the second largest
      globally. Stigma and discrimination are major barriers to testing, treatment
      uptake, and adherence. In this review, we synthesized information on research
      studies, policies, and programmes related to HIV-stigma in Nigeria. This was with
      a view to identify critical areas that research and programmes must address in
      order to accelerate the progress towards zero (new infections, discrimination,
      and death) target by year 2030. Existing studies were mostly devoted to stigma
      assessment using varieties of measures. Research, policies, and programmes in the
      past two decades have made very useful contributions to stigma reduction. We
      identified the need for a consistent, valid, and objective measure of stigma at
      different levels of the HIV response. Nigeria does not lack relevant policies;
      what needs to be strengthened are design, planning, implementation, monitoring,
      and evaluation of context-specific stigma reduction programmes.

PMID- 29445546
TI  - Circulating Angiogenic Growth Factors in Diabetes Patients with Peripheral
      Arterial Disease and Exertional Leg Pain in Ghana.
AB  - Objective: Peripheral arterial disease (PAD) is a common complication of
      diabetes, associated with impairment in angiogenesis. Angiogenesis is regulated
      by angiogenic growth factors such as angiopoietin 1 (Ang-1), Ang-2, and vascular
      endothelial growth factor (VEGF). We studied the association between angiogenic
      growth factors versus PAD and exertional leg symptoms in diabetes patients in
      Ghana. Method: In this cross-sectional study, ankle-brachial index was measured
      with oscillometrically and exertional leg symptoms were screened with Edinburgh
      claudication questionnaire in 140 diabetes patients and 110 nondiabetes
      individuals. Circulating levels of Ang-1, Ang-2, and VEGF were measured with
      immunosorbent assay. Results: The prevalence of PAD and exertional leg pain was
      16.8% and 24.8%, respectively. Compared to non-PAD participants, PAD patients had
      higher VEGF levels [85.8 (37.5-154.5) versus 57.7 (16.6-161.1) p = 0.032] and
      lower Ang-1 levels [31.3 (24.8-42.6) versus 40.9 (28.2-62.1), p = 0.017]. In
      multivariable logistic regression, patients with exertional leg pain had
      increased the odds of plasma Ang-2 levels [OR (95% CI): 2.08 (1.08-6.41), p =
      0.036]. Conclusion: Diabetes patients with PAD and exertional leg pain have
      imbalance in angiogenic growth factors, indicating impaired angiogenesis. In
      patients with exertional leg pains, Ang-2 may be an important biomarker.

PMID- 29445548
TI  - Comparison of Algorithms for the Detection of Enteroviruses in Stool Specimens
      from Children Diagnosed with Acute Flaccid Paralysis.
AB  - This study was designed to compare both the cell culture dependent and
      independent enterovirus detection algorithms recommended by the WHO and assess
      how either might impact our perception of the diversity of enterovirus types
      present in a sample. Sixteen paired samples (16 isolates from RD cell culture and
      their corresponding stool suspension, i.e., 32 samples) from AFP cases in Nigeria
      were analyzed in this study. All the samples were subjected to RNA extraction,
      cDNA synthesis, the WHO recommended RT-snPCR, and its modification. Amplicons
      were sequenced and strains identified. Enterovirus diversity was the same between
      the isolates and fecal suspension for the control and five of the samples. It
      was, however, different for the remaining 10 (62.5%) samples. Nine (CV-B4, E6,
      E7, E13, E14, E19, E29, EV-B75, and EV-B77) and five (CV-A1, CV-A11, CV-A13, EV
      C99, and PV2) EV-B and EV-C types, respectively, were detected. Particularly, E19
      and EV-B75 were only recovered from the isolates while E14, EV-B77, CV-A11, and
      CV-A13 were only recovered from fecal suspension. Both the cell culture dependent
      and independent protocols bias our perception of the diversity of enterovirus
      types present in a sample. Hence, effort should be directed at harmonizing both
      for increased sensitivity.

PMID- 29445547
TI  - Temporal Regulation of fim Genes in Uropathogenic Escherichia coli during
      Infection of the Murine Urinary Tract.
AB  - Uropathogenic Escherichia coli (UPEC) adhere to cells in the human urinary tract
      via type 1 pili that undergo phase variation where a 314-bp fimS DNA element
      flips between Phase-ON and Phase-OFF orientations through two site-specific
      recombinases, FimB and FimE. Three fim-lux operon transcriptional fusions were
      created and moved into the clinical UPEC isolate NU149 to determine their
      temporal regulation in UPEC growing in the urinary tract. Within murine urinary
      tracts, the UPEC strains demonstrated elevated transcription of fimA and fimB
      early in the infection, but lower transcription by the fifth day in murine
      kidneys. In contrast, fimE transcription was much lower than either fimA or fimB
      early, increased markedly at 24 h after inoculation, and then dropped five days
      after inoculation. Positioning of fimS was primarily in the Phase-ON position
      over the time span in UPEC infected bladders, whereas in UPEC infected murine
      kidneys the Phase-OFF orientation was favored by the fifth day after inoculation.
      Hemagglutination titers with guinea pig erythrocytes remained constant in UPEC
      growing in infected murine bladders but fell substantially in UPEC infected
      kidneys over time. Our results show temporal in vivo regulation of fim gene
      expression in different environmental niches when UPEC infects the murine urinary
      tract.

PMID- 29445550
TI  - Neural Mechanisms of Autonomic Dysfunction in Neurological Diseases.

PMID- 29445549
TI  - Relationship between Insulin Levels and Nonpsychotic Dementia: A Systematic
      Review and Meta-Analysis.
AB  - Objectives: To explore the relationship between insulin levels and nonpsychotic
      dementia. Methods: Six electronic databases (PubMed, Cochrane, SCI, CNKI, VIP,
      and Wanfang) were searched from January 1, 2007, to March 1, 2017. Experimental
      or observational studies that enrolled people with nonpsychotic dementia or
      abnormal insulin levels in which insulin levels or MMSE scores (events in
      nonpsychotic dementia) were the outcome measures. Random-effects models were
      chosen for this meta-analysis. Sample size, mean, s.d., and events were primarily
      used to generate effect sizes (with the PRIMA registration number
      CRD42017069860). Results: 50 articles met the final inclusion criteria. Insulin
      levels in cerebrospinal fluid were lower (Hedges' g = 1.196, 95% CI = 0.238 to
      2.514, and P = 0.014), while the levels in peripheral blood were higher in
      nonpsychotic dementia patients (Hedges' g = 0.853 and 95% CI = 0.579 to 1.127),
      and MMSE scores were significantly lower in the high insulin group than in the
      healthy control group (Hedges' g = 0.334, 95% CI = 0.249 to 0.419, and P =
      0.000). Conclusions: Our comprehensive results indicate that blood insulin levels
      may increase in patients with nonpsychotic dementia.

PMID- 29445552
TI  - Oncocytes in Mucoepidermoid Carcinoma of the Palate: Diagnostic Challenges.
AB  - The origin of a salivary gland tumour is attributed to cells at various levels of
      differentiation which present histologically as diverse tissues and cellular
      patterns. Mitochondria-rich, eosinophilic oncocytes are cells commonly
      encountered in salivary gland neoplasms. We report a case of mucoepidermoid
      carcinoma (MEC) in the palate of a 43-year-old female that exhibited a prominent
      oncocytic component. While the parotid and submandibular glands have been
      reported as predominant sites for oncocytic MEC (OMEC), the palate and minor
      salivary glands are rare sites for occurrence. Also, most of the reported cases
      of OMEC have been histologically of low-grade mucoepidermoid carcinoma with large
      cystic spaces and good prognosis. In this article, we discuss the differential
      diagnosis and diagnostic workup of an MEC presenting with oncocytes.

PMID- 29445551
TI  - Effects of Various Extents of High-Frequency Hearing Loss on Speech Recognition
      and Gap Detection at Low Frequencies in Patients with Sensorineural Hearing Loss.
AB  - This study explored whether the time-compressed speech perception varied with the
      degree of hearing loss in high-frequency sensorineural hearing loss (HF SNHL)
      individuals. 65 HF SNHL individuals with different cutoff frequencies were
      recruited and further divided into mildly, moderately, and/or severely affected
      subgroups in terms of the averaged thresholds of all frequencies exhibiting
      hearing loss. Time-compressed speech recognition scores under both quiet and
      noisy conditions and gap detection thresholds within low frequencies that had
      normal thresholds were obtained from all patients and compared with data from 11
      age-matched individuals with normal hearing threshold at all frequencies.
      Correlations of the time-compressed speech recognition scores with the extents of
      HF SNHL and with the 1 kHz gap detection thresholds were studied across all
      participants. We found that the time-compressed speech recognition scores were
      significantly affected by and correlated with the extents of HF SNHL. The time
      compressed speech recognition scores also correlated with the 1 kHz gap detection
      thresholds except when the compression ratio of speech was 0.8 under quiet
      condition. Above all, the extents of HF SNHL were significantly correlated with
      the 1 kHz gap thresholds.

PMID- 29445553
TI  - S. lugdunensis Native-Joint Septic Arthritis: Case Report and Review of the
      Literature.
AB  - Staphylococcus lugdunensis is a skin commensal classified as a coagulase-negative
      Staphylococcus (CoNS). Though CoNS is typically associated with less aggressive
      clinical disease than Staphylococcus aureus, there is growing awareness that S.
      lugdunensis may be as virulent as S. aureus. The association between S.
      lugdunensis and infective endocarditis is well known, but few reports of native
      joint disease with this organism exist. We report a case a 28-year-old male with
      no prior medical problems presenting with native-joint septic arthritis. Cultures
      grew S. lugdunensis. To our knowledge, this is the fifth case reported in the
      literature.

PMID- 29445554
TI  - Ogilvie's Syndrome after Cesarean Section: Case Report in Saudi Arabia and
      Management Approach.
AB  - Background: Acute colonic pseudoobstruction or Ogilvie's syndrome is a rare
      entity that is characterized by acute dilatation of the colon without any
      mechanical obstruction. It is usually associated with medical disease or surgery
      and rarely occurs spontaneously. If not diagnosed early, Ogilvie's syndrome may
      cause bowel ischemia and perforation. Case: A G7P4+2, 40-year-old woman, who is a
      known case of gestational diabetes mellitus during her current pregnancy, four
      previous cesarean sections, two early pregnancy losses at six-week gestation, and
      hypothyroidism, underwent uncomplicated elective cesarean section, after which
      she complained of abdominal distention. Conclusion: Ogilvie's syndrome is a rare
      condition yet of interest to obstetricians, midwifery staff, and general surgeons
      because its early diagnosis and prompt treatment are the keystones to avoid any
      subsequent fatal complications. This case report reviews the clinical
      characteristics, diagnostic methods, and management of Ogilvie's syndrome.
      Moreover, we suggest a management approach to help in early diagnosis and prompt
      management to improve the outcome of this potentially serious condition.

PMID- 29445555
TI  - Metastatic Recurrence of Typical Pulmonary Carcinoid Accompanied by Carcinoid
      Syndrome, Successfully Treated with Octreotide LAR.
AB  - We present a case of metastatic recurrence of carcinoid tumor accompanied by
      carcinoid syndrome in a 68-year-old Japanese man, 12 years after resection of
      typical pulmonary carcinoid. Histopathologic examination from percutaneous liver
      biopsy revealed metastatic typical carcinoid. Clinical symptoms gradually
      improved after administration of octreotide LAR. Two years after starting
      treatment, the disease remains well controlled. This case report illustrates the
      possibility of antiproliferative effects of octreotide LAR on typical pulmonary
      carcinoid.

PMID- 29445556
TI  - Immunotherapy for Metastatic Melanoma with Right Atrial Involvement in a Patient
      with Rheumatoid Arthritis.
AB  - Prognosis for metastatic melanoma has improved significantly with the use of
      immune checkpoint inhibitors. Given improvements in survival, aggressive surgical
      treatment may be considered in patients with life-threatening complications from
      their disease that would not otherwise be considered in advanced disease.
      Patients with preexisting autoimmune diseases or prior immune-related adverse
      events from therapy are largely excluded from clinical trials. Concerns exist
      that immunotherapy in these patients could worsen autoimmune disease or increase
      the risk of developing additional immune-related adverse events on therapy. We
      present a case of a patient with rheumatoid arthritis that presented with
      obstructive heart failure secondary to melanoma that had metastasized to the
      right atrium. After aggressive surgical resection to stabilize him from his life
      threatening heart failure, he was treated with ipilimumab, which was stopped due
      to an immune-related adverse event. He was then started on pembrolizumab and had
      a durable response to therapy. Aggressive surgical treatment should be considered
      in patients with a cancer that may respond to immunotherapy. Furthermore, some
      patients with preexisting autoimmune disease may be safely treated with
      checkpoint inhibition therapy, and patients with a severe immune toxicity from
      one class may successfully be treated with an alternate class.

PMID- 29445557
TI  - Benign Recurrent Sixth Nerve Palsy in a Child.
AB  - Benign recurrent sixth nerve palsy in children is rare. It typically occurs
      following viral illness or immunization, and prognosis is usually excellent.
      However, it is always a diagnosis of exclusion given the more serious alternative
      causes. Therefore, a thorough examination with brain imaging is recommended. The
      authors report a child with six recurrent episodes of isolated benign sixth nerve
      palsy.

PMID- 29445558
TI  - Delayed Radial Nerve Palsy after Closed Reduction of a Pediatric Humeral Shaft
      Fracture.
AB  - Humeral shaft fractures are common in the United States and may be associated
      with radial nerve injuries due to their close anatomic relationship in the spiral
      groove. Most radial nerve palsies are found at presentation due to the initial
      trauma; however, they can present secondary to orthopaedic intervention following
      reduction. In this case report, we present a case of delayed radial nerve palsy
      in a pediatric patient that was identified four days after closed reduction and
      splinting which required open reduction, nerve exploration, and internal
      fixation. Fortunately, full motor and sensory recovery was observed at 6 weeks
      post-op. A unique aspect of this case is that immediate postreduction exam in the
      emergency department showed no signs of injury or entrapment of the radial nerve.

PMID- 29445559
TI  - A Rare Case Report and Literature Review of External Auditory Canal Cholesteatoma
      with Circumferential Destruction of Canal Wall Exposing Facial Nerve.
AB  - External auditory canal cholesteatoma (EACC) is a rare condition with an
      estimated incidence of 1.2 per 1000 new otological patients. It is often mistaken
      with keratosis obturans. We discuss an extensive primary EACC with an aural polyp
      in a male which was managed by modified radical mastoidectomy.

PMID- 29445560
TI  - The Partial Duplication of the 5' Segment of KMT2A Revealed KMT2A-MLLT10
      Rearrangement in a Boy with Acute Myeloid Leukemia.
AB  - The duplication of 5' segment of KMT2A is a rare molecular event in childhood
      leukemia, and the influence on prognosis is unknown. Here, we report on a boy who
      developed acute monocytic leukemia. Fluorescence in situ hybridization revealed
      the duplication of the 5' segment with 2 normal alleles at KMT2A which was
      eventually found to be fused with MLLT10. Chemotherapy promptly induced the first
      complete remission in the patient at our facility, and the patient remained in
      first complete remission with negative minimal residual disease at 3.5 years from
      diagnosis. Our case is similar to two previously reported patients who had
      partial duplication of the 5' segment of KMT2A with a KMT2A-MLLT10 rearrangement.
      Further studies and experience with this cryptic translocation may shed more
      light on the management of acute myeloid leukemia.

PMID- 29445561
TI  - Thoracic Paravertebral Mass as an Infrequent Manifestation of IgG4-Related
      Disease.
AB  - Case: A 50-year-old African American male presented with abdominal pain and
      significant weight loss. On physical examination, he had parotid and
      submandibular gland enlargement associated with right eye proptosis. Computed
      tomography showed a thoracic paravertebral soft tissue mass, enlarged lymph
      nodes, and ascending aortic aneurysm. Laboratory results were remarkable for
      elevated total IgG and IgG4 subclass. The submandibular gland pathology revealed
      chronic sclerosing sialadenitis, with a large subset of inflammatory cells
      positively staining for IgG4. The histology of the paravertebral mass
      demonstrated fibrosclerosis with increased lymphocytic infiltrate, associated
      with increased IgG4 plasma cells. He was diagnosed with immunoglobulin G4-related
      disease (IgG4-RD). Steroid therapy initially yielded improvement; however, after
      steroids were stopped, there was disease recurrence. Prednisone was restarted,
      and the plan was to start him on rituximab. Interestingly, the patient's brother
      also had IgG4-RD. Conclusion: IgG4-RD can present as a paravertebral mass which
      is usually responsive to steroids; however, recurrent and resistant disease can
      be seen for which steroid-sparing agents such as rituximab should be considered.
      In addition, to the best of our knowledge, this is the first reported case of
      IgG4-RD in two family members presenting as a paravertebral mass, highlighting an
      exciting area for more research in the future.

PMID- 29445562
TI  - Erratum to "Torsion of Hydrosalpinx with Concurrent Acute Cholecystitis: Case
      Report and Review of Literature".
AB  - [This corrects the article DOI: 10.1155/2016/5424092.].

PMID- 29445563
TI  - Eculizumab for Thrombotic Microangiopathy Associated with Antibody-Mediated
      Rejection after ABO-Incompatible Kidney Transplantation.
AB  - Thrombotic microangiopathy is a form of antibody-mediated rejection (ABMR): it is
      the main complication of ABO-incompatible (ABOi) kidney transplantation (KT).
      Herein, we report on two cases of ABMR with biological and histological features
      of thrombotic microangiopathy (TMA) that were treated by eculizumab after ABOi
      KT. The first patient presented with features of TMA at postoperative day (POD)
      13. Because of worsening biological parameters and no recovery of kidney
      function, despite seven sessions of immunoadsorption, a salvage therapy of
      eculizumab was started on POD 23. Kidney function slightly improved during the
      first 4 months after transplantation. Eculizumab was stopped at month 4. However,
      kidney function worsened progressively, leading to dialysis at month 13 after
      transplantation. The second patient presented with features of TMA at POD 1. In
      addition to immunoadsorption therapy, eculizumab was started on POD 6. Kidney
      function improved. Eculizumab was stopped on POD 64 and immunoadsorption sessions
      were stopped on POD 102. At the last follow-up (after 9 months), eGFR was at 43
      mL/min/1.73 m2. Our case reports show the beneficial effect of eculizumab to
      treat ABMR after ABOi KT. However, it should be given early after diagnosing TMA
      associated with ABMR.

PMID- 29445564
TI  - 3-DOF Force-Sensing Micro-Forceps for Robot-Assisted Membrane Peeling: Intrinsic
      Actuation Force Modeling.
AB  - Membrane peeling is a challenging procedure in retinal microsurgery, requiring
      careful manipulation of delicate tissues by using a micro-forceps and exerting
      very fine forces that are mostly imperceptible to the surgeon. Previously, we
      developed a micro-forceps with three integrated fiber Bragg grating (FBG) sensors
      to sense the lateral forces at the instrument's tip. However, importantly this
      architecture was insufficient to sense the tissue pulling forces along the
      forceps axis, which may be significant during membrane peeling. Our previous 3
      DOF force sensing solutions developed for pick tools are not appropriate for
      forceps tools due to the motion and intrinsic forces that develop while
      opening/closing the forceps jaws. This paper presents a new design that adds
      another FBG attached to the forceps jaws to measure the axial loads. This
      involves not only the external tool-to-tissue interactions that we need to
      measure, but also the adverse effect of intrinsic actuation forces that arise due
      to the elastic deformation of jaws and friction. In this study, through
      experiments and finite element analyses, we model the intrinsic actuation force.
      We investigate the effect of the coefficient of friction and material type
      (stainless steel, titanium, nitinol) on this model. Then, the obtained model is
      used to separate the axial tool-to-tissue forces from the raw sensor
      measurements. Preliminary experiments and simulation results indicate that the
      developed linear model based on the actuation displacement is feasible to
      accurately predict the axial forces at the tool tip.

PMID- 29445566
TI  - Patients affected by endemic pemphigus foliaceus in Colombia, South America
      exhibit autoantibodies to optic nerve sheath envelope cell junctions.
AB  - Background: The majority of the patients affected by a new variant of endemic
      pemphigus foliaceus in El Bagre, Colombia (El Bagre EPF or pemphigus Abreu-Manu),
      have experienced vision problems; we have previously reported several ocular
      abnormalities. Methods: Here, we aimed to investigate reactivity to optic nerves
      in these patients. We utilized bovine, rat and mouse optic nerves, and performed
      immunofluorescence and confocal microscopy to test for optical nerve
      autoreactivity. We tested 45 patients affected by this disease and 45 controls
      from the endemic area matched by age, sex and work activity. Results: Overall, 37
      of the 45 patient sera reacted to the optic nerve envelope that is composed of
      leptomeninges; the reactivity was polyclonal and present mostly at the cell
      junctions (P < 0.001). The immune response was directed against optic nerve
      sheath cell junctions and the vessels inside it, as well as other molecules
      inside the nerve. No control cases were positive. Of interest, all the patient
      autoantibodies co-localized with commercial antibodies to desmoplakins I-II,
      myocardium-enriched zonula occludens-1- associated protein (MYZAP), armadillo
      repeat gene deleted in velo-cardio-facial syndrome (ARVCF), and plakophilin-4
      (p0071) from Progen Biotechnik (P < 0.001). Conclusion: We conclude that the
      majority of the patients affected by pemphigus Abreu-Manu have autoantibodies to
      optic nerve sheath envelope cell junctions. These antibodies also co-localize
      with armadillo repeat gene deleted in velo-cardio-facial syndrome, p0071 and
      desmoplakins I-II. The clinical significance of our findings remains unknown.

PMID- 29445565
TI  - Super-Resolution Community Detection for Layer-Aggregated Multilayer Networks.
AB  - Applied network science often involves preprocessing network data before applying
      a network-analysis method, and there is typically a theoretical disconnect
      between these steps. For example, it is common to aggregate time-varying network
      data into windows prior to analysis, and the trade-offs of this preprocessing are
      not well understood. Focusing on the problem of detecting small communities in
      multilayer networks, we study the effects of layer aggregation by developing
      random-matrix theory for modularity matrices associated with layer-aggregated
      networks with N nodes and L layers, which are drawn from an ensemble of Erdos
      Renyi networks with communities planted in subsets of layers. We study phase
      transitions in which eigenvectors localize onto communities (allowing their
      detection) and which occur for a given community provided its size surpasses a
      detectability limit K* . When layers are aggregated via a summation, we obtain
      [Formula: see text], where T is the number of layers across which the community
      persists. Interestingly, if T is allowed to vary with L, then summation-based
      layer aggregation enhances small-community detection even if the community
      persists across a vanishing fraction of layers, provided that T/L decays more
      slowly than ??(L-1/2). Moreover, we find that thresholding the summation can, in
      some cases, cause K* to decay exponentially, decreasing by orders of magnitude in
      a phenomenon we call super-resolution community detection. In other words, layer
      aggregation with thresholding is a nonlinear data filter enabling detection of
      communities that are otherwise too small to detect. Importantly, different
      thresholds generally enhance the detectability of communities having different
      properties, illustrating that community detection can be obscured if one analyzes
      network data using a single threshold.

PMID- 29445567
TI  - An unusual lesion on the nose: microvenular hemangioma.
AB  - Microvenular hemangioma (MVH) is an acquired, benign type of hemangioma that
      usually manifests itself as a solitary, slowly growing, red to violaceous,
      asymptomatic papule, plaque or nodule. It is typically located on the trunk or
      extremities of young adults. It can be difficult to differentiate MVH from other
      types of hemangioma and Kaposi sarcoma. Herein we report a case of MVH unusual
      for its location, age of onset, and morphologic features. A 62-year-old man
      complained of an asymptomatic, bluish-red discoloration on the tip of his nose
      that had been present for two years. Dermatologic examination showed a violaceous
      patch 2 * 2 cm in diameter with indistinct borders. Incisional biopsy revealed
      irregularly branched small or medium-sized vascular spaces lined with benign
      endothelial cells, positive for CD34 and negative for HHV-8. MVH is a rare
      lesion, and less than 70 cases have been published to date. A review of 40
      reported cases revealed that 15% of MVH patients were over 40 years of age and
      only 3% of the cases showed macules or patches. A literature survey showed only
      two cases of MVH located on the facial region, one on the chin and the other on
      the cheek. Our case was unique for its location and interesting for other rarely
      encountered features. MVH should be considered in the differential diagnoses of
      vascular lesions on nasal skin.

PMID- 29445569
TI  - Glutathione for skin lightening: a regnant myth or evidence-based verity?
AB  - The recent hype surrounding the antimelanogenic properties of glutathione has
      resulted in physicians frequently administering it as a "wonder" drug for skin
      lightening and treatment of hyperpigmentation, especially in ethnic populations
      with darker skin tones. This phenomenon has seen a recent surge owing to
      aggressive marketing and capitalization of pharma-cosmeceutical companies.
      However, the unbridled and prodigal use of it, especially as a parenteral
      formulation, seems unjustified, given the lacunae in our knowledge about its
      antimelanogenic potential, limited clinical evidence favoring its role in skin
      lightening, and the statutory ban/advisory issued by certain federal agencies.
      Even though parenteral glutathione is approved only for severe liver disorders
      and for prevention of chemotherapy associated neurotoxicity, the lack of
      statutory laws governing the use of systemic glutathione in most countries has
      contributed to its unchecked use for skin lightening. The current clinical
      evidence of intravenous glutathione for skin lightening is limited to a single
      study with a dubious study design and apparently flawed analysis of results,
      casting doubt on the drug's efficacy and reported adverse effects. Two studies
      evaluating oral/sublingual administration and one trial involving the use of
      topical glutathione reported good safety profile and appreciable but reversible
      results on skin tone. In this article, we shall review and discuss the current
      status of glutathione as a skin lightening agent and address the sundry
      unanswered queries regarding the dosage, duration of use and longevity of accrued
      effects based on clinical evidence and recent insights into its antimelanogenic
      mechanism.

PMID- 29445568
TI  - Satisfactory treatment of a large connective tissue nevus with intralesional
      steroid injection.
AB  - Collagenoma is a type of connective tissue nevi, a rare hamartomatous
      malformation characterized by the predominant proliferation of normal collagen
      fibers and normal, decreased, or increased elastic fibers. Collagenomas present
      as multiple or solitary, hereditary or sporadic, asymptomatic, skin-colored
      papules, nodules, and plaques with variable sizes, and are usually located on the
      trunk, arm, and back. Here, we report on a 14-year-old boy who presented with an
      isolated giant collagenoma of the frontal area that dramatically responded to
      intralesional triamcinolone acetonide.

PMID- 29445570
TI  - A new perspective on the nail plate for treatment of ingrown toenail.
AB  - Background: Our routine treatment for ingrown toenail was removal of the
      surrounding soft tissue and shortening the bone of the distal phalanx. We
      determined the range and volume of excision based on our experience without an
      objective standard and routinely performed avulsion of the nail plate. Objective:
      To take the nail plate as an objective mark during surgical treatment of ingrown
      toenail to ensure accurate excision. Patients and Methods: Fifteen patients with
      ingrown toenails were treated with this technique. We used the lateral borders of
      the nail plate as a landmark to determine the volume of soft tissue surrounding
      the nail plate and distal phalanx to be removed. No avulsion of nail plate was
      performed. Results: No recurrence was observed during the follow-up period, which
      ranged from 24 to 35 months (29.9 months on average). The visual analog scale for
      pain showed significant pain relief in the patients. The Vancouver Scar Scale
      showed acceptable cosmetic outcomes. The width of excised skin ranged from 3.5 to
      6.2 mm (5.0 mm on average). Conclusion: The use of the lateral borders of the
      nail plate as a landmark for surgical intervention of ingrown toenail offered
      excellent outcomes and reduced loss of healthy tissues.

PMID- 29445571
TI  - Immunoreactivity of Wilms tumor 1 (WT1) as an additional evidence supporting
      hemangiomatous rather than inflammatory origin in the etiopathogenesis of
      angiolymphoid hyperplasia with eosinophilia.
AB  - Background: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare vascular
      proliferative disorder mainly located in the periauricular region. The
      etiopathogenesis of ALHE is unknown, and it is still controversial as to whether
      the entity represents a benign vascular neoplasm or an inflammatory process. Aim:
      Recently, the intracytoplasmic staining pattern of Wilms tumor 1 (WT1) on
      immunohistochemistry has highlighted true vascular neoplasms, such as
      microvenular hemangioma, tufted angioma, and spindle cell hemangioma, which has
      made it helpful to distinguish ALHE from vascular malformations, as there is a
      negative staining pattern in the other entities. We aimed to investigate the
      immunoreactivity of ALHE specimens for WT1 as well as glucose transporter protein
      1 (GLUT1) immunohistochemistry, an important and sensitive marker for the
      diagnosis of infantile hemangioma, which recently has been described to label
      other hemangiomas, such as verrucous hemangioma. Material and methods: Clinical
      data and histopathological specimens from patients diagnosed with ALHE were
      reviewed, and immunohistochemical staining and microscopic analysis for WT-1 and
      GLUT1 were performed. Results: Intracytoplasmic endothelial staining of WT1 was
      detected in 19 of 20 ALHE specimens. GLUT1 was not detected in any ALHE specimen.
      Conclusions: We conclude that ALHE may represent a true hemangioma (i.e., benign
      vascular neoplasia) characterized by an eosinophil- and lymphocyte-rich
      inflammatory component as opposed to the reactive inflammatory dermatosis with a
      positive intracytoplasmic staining pattern for WT1. As far as we are aware, WT1
      staining for ALHE has not been described to date.

PMID- 29445572
TI  - Dermoscopy of a rare case of linear syringocystadenoma papilliferum with review
      of the literature.
AB  - Syringocystadenoma papilliferum (SCAP) is a benign hamartomatous tumor arising
      from pluripotent cells with either apocrine or eccrine differentiation. We report
      a rare case of de novo linear SCAP in a 12-year-old female child with lesions
      over the chest along with the dermoscopic findings.

PMID- 29445573
TI  - Standard dermoscopy and videodermoscopy as tools for medical student dermatologic
      education.

PMID- 29445574
TI  - Linear verrucous hemangioma-a rare case and dermoscopic clues to diagnosis.
AB  - Verrucous hemangioma (VH) is a rare, congenital and localized vascular
      malformation, which usually presents as warty, bluish, vascular papules, plaques,
      or nodules, mainly on the lower extremities. Linear presentation of the disease
      is rare. A deep biopsy is necessary to confirm the clinical diagnosis by
      histopathological examination, with dermoscopy acting as a useful tool for
      evaluating the precise vascular structure. Here, we report on a 13-year-old
      female child with linear VH presenting over her foot since infancy and
      dermoscopic findings of VH along with the clinical-pathologic features.

PMID- 29445575
TI  - A red nodule of the scalp.

PMID- 29445576
TI  - Solitary orange papule on the back of a middle-aged man.

PMID- 29445577
TI  - Mucoscopy in lingual varicosities.

PMID- 29445578
TI  - Whitish halo on a papular pigmented lesion.

PMID- 29445579
TI  - Patient with confirmed LEOPARD syndrome developing multiple melanoma.
AB  - LEOPARD syndrome, also known as Gorlin syndrome II, cardiocutaneous syndrome,
      lentiginosis profusa syndrome, Moynahan syndrome, was more recently coined as
      Noonan syndrome with multiple lentigines (NSML), inside the RASopathies.
      Historically, the acronym LEOPARD refers to the presence of distinctive clinical
      features such as: lentigines (L), electrocardiographic/conduction abnormalities
      (E), ocular hypertelorism (O), pulmonary stenosis (P), genital abnormalities (A),
      retardation of growth (R), and sensorineural deafness (D). This condition is
      identified in 85% of patients with phenotype hallmarks caused by presence a
      germline point mutation in PTPN11 gene. Association of melanoma to NSML seems to
      be rare: to our knowledge, two patients so far were reported in the literature.
      We herein present a patient diagnosed with LEOPARD syndrome, in whom molecular
      investigation confirmed the presence of the c.1403C>T mutation in exon 12 of the
      PTPN11 gene, who developed four superficial spreading melanomas and three
      atypical lentiginous hyperplasias. Three of the melanomas were achromic or
      hypochromic, three were in situ, and one had a Breslow index under 0.5 mm.
      Dermoscopic examination showed some characteristic white structures in most of
      the lesions, which were a signature pattern and a key for the diagnosis.

PMID- 29445580
TI  - The role of reflectance confocal microscopy in a case of Bowen's disease
      difficult to diagnose.
AB  - There have been limited reports describing reflectance confocal microscopy (RCM)
      features of Bowen's disease (BD). Herein, we describe the RCM features of a
      pigmented BD with atypical dermoscopic features, mimicking a melanoma. This case
      highlights the importance of RCM in a challenging BD.

PMID- 29445581
TI  - Eruptive nevi after burn injury.
AB  - Eruptive melanocytic nevi (EMN) is an unusual phenomenon characterized by the
      abrupt development of multiple melanocytic nevi over weeks to months in
      association with an underlying trigger. The underlying mechanisms are not fully
      understood, however, they have been associated with a variety of conditions. EMN
      is relatively uncommon and might be underreported due to the absence of close
      monitoring, insufficient recognition, and the presumed benign course of the
      condition. We describe the first case report of acral EMN associated with a burn
      wound on a 2-year-old child. Familiarity is important to differentiate EMN from
      neoplasms.

PMID- 29445582
TI  - Dermoscopic and reflectance confocal microscopy features of two cases of vulvar
      basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) is the most common malignant skin cancer. Its genital
      localization is rare, and the diagnosis in this site could be challenging. Here,
      we report two patients with vulvar BCC and describe their clinical, dermoscopic
      and in vivo and ex vivo reflectance confocal microscopic (RCM) features.
      Dermoscopy and RCM can be useful tools for helping the clinical diagnosis of
      vulvar BCC and for identifying the correct surgical margins.

PMID- 29445583
TI  - Deep sustained response to daratumumab monotherapy associated with T-cell
      expansion in triple refractory myeloma.
AB  - Background: Daratumumab, a human CD38 monoclonal antibody that has direct on
      tumor and immunomodulatory mechanisms of action, demonstrated clinical benefit as
      monotherapy or in combination with established regimens in patients with multiple
      myeloma with one or more prior lines of therapy. Case presentation: A male
      patient, who was 70 years of age at the time of diagnosis of multiple myeloma in
      2011, relapsed after five lines of therapy, including autologous stem cell
      transplantation. The patient's disease, which was considered high risk with a
      deletion of chromosome 17p, advanced quickly and was triple refractory 2 years
      after diagnosis leaving few treatment options. He was treated with daratumumab
      monotherapy in the SIRIUS clinical trial resulting in a stringent complete
      response and clearance of minimal residual disease. The duration of the patient's
      clinical response is now over 3.5 years without relapse, compared with a median
      of 7.6 months for similarly treated patients. The patient's immunophenotype
      revealed CD8+ T-cell expansion, clonal expansion of the T-cell receptor
      repertoire, and decreases in regulatory T cells during daratumumab therapy,
      suggesting a robust adaptive immune response. This immune response was still
      present 32 months into daratumumab therapy. Conclusions: The results from this
      case report showed that a patient with advanced multiple myeloma, who had
      exhausted all treatment options with existing regimens, mounted an ongoing, deep,
      and durable response to daratumumab monotherapy. Further investigation of the
      immunologic profile provided additional patient-level evidence of an
      immunomodulatory mechanism of action of daratumumab.Trial registration
      ClinicalTrials.gov Identifier number NCT01985126. Submitted 22 July 2013.

PMID- 29445584
TI  - Acid-Sensing Ion Channel 1a Regulates Fate of Rat Nucleus Pulposus Cells in Acid
      Stimulus Through Endoplasmic Reticulum Stress.
AB  - Acid-sensing ion channel 1a (ASIC1a) participates in human intervertebral disc
      degeneration (IVDD) and regulates the destiny of nucleus pulposus cells (NPCs) in
      acid stimulus. However, the mechanism of ASIC1a activation and its downstream
      pathway remain unclear. Endoplasmic reticulum (ER) stress also participates in
      the acid-induced apoptosis of NPCs. The main purpose of this study was to
      investigate whether there is any connection between ASIC1a and ER stress in an
      acid-induced nucleus pulposus degeneration model. The IVDs of Sprague-Dawley rats
      were stained by immunohistochemical staining to evaluate the expression of ASIC1a
      in normal and degenerated rat nucleus pulposus. ASIC1a expression was also
      quantified by quantitative real-time-polymerase chain reaction and Western
      blotting analysis. NPCs were exposed to the culture media with acidity at pH 7.2
      and 6.5 for 24 h, with or without 4-phenylbutyrate (4-PBA, a blocker of the ER
      stress pathway). Cell apoptosis was examined by Annexin V/Propidium Iodide (PI)
      staining and was quantified using flow cytometry analysis. ASIC1a-mediated
      intracellular calcium was determined by Ca2+ imaging using Fura-2-AM. Acidity
      induced changes in ER stress markers were studied using Western blotting
      analysis. In vivo, ASIC1a expression was upregulated in natural degeneration. In
      vitro, acid stimulus increased intracellular calcium levels, but this effect was
      blocked by knockdown of ASIC1a, and this reversal was partly inhibited by 4-PBA.
      In addition, blockade of ASIC1a reduced expression of ER stress markers,
      especially the proapoptotic markers. ASIC1a partly regulates ER stress and
      promotes apoptosis of NPCs under acid stimulus and may be a novel therapeutic
      target in IVDD.

PMID- 29445585
TI  - Engineered Human Stem Cell Microenvironments.
AB  - Stem cells have the ability to self-renew and differentiate into specialized cell
      types, and, in the human body, they reside in specialized microenvironments
      called "stem cell niches." Although several niches have been described and
      studied in vivo, their functional replication in vitro is still incomplete. The
      in vitro culture of pluripotent stem cells may represent one of the most advanced
      examples in the effort to create an artificial or synthetic stem cell niche. A
      focus has been placed on the development of human stem cell microenvironments due
      to their significant clinical implications, in addition to the potential
      differences between animal and human cells. In this concise review we describe
      the advances in human pluripotent stem cell culture, and explore the idea that
      the knowledge gained from this model could be replicated to create synthetic
      niches for other human stem cell populations, which have proven difficult to
      maintain in vitro.

PMID- 29445587
TI  - Training in robotic thoracic surgery.
AB  - The best way to teach robotic thoracic surgery is still being decided. New
      trainees, experienced video-assisted thoracoscopic surgery (VATS) surgeons, and
      predominantly open surgeons each have different needs when it comes to learning
      robotic surgery. The data shows that the learning curve and ability to learn
      robotics initially appears to be shorter and easier than surgeons learning VATS.
      Though the absolute best method for teaching is still under investigation,
      multiple centers have started to create systematic methods of teaching robotic
      surgery that increases resident autonomy while still protecting the patient.

PMID- 29445588
TI  - The Very Experienced Time-honoUred Surgeons (VETUS) project.
AB  - Senior surgeons who completed their formal surgical training before the video
      assisted thoracoscopic surgery (VATS) lobectomy era have had more experience with
      lobectomy via thoracotomy while their thoracoscopic training background contrasts
      from younger surgeons. However, this does not seem to have an unfavourable effect
      on their performance. Despite the literature recognising the critical points of
      influence of the learning curve for resident surgeons, limited data are focusing
      on the incremental performance of VATS lobectomy by senior surgeons. The Very
      Experienced Time-honoUred Surgeons (VETUS) project aims to understand this trend
      in the VATS group and to introduce an approach to the VATS lobectomy involving
      senior surgeon. The VETUS project is based on a self-assessment program where the
      senior surgeon (independently and in complete anonymity) follows a 1-year
      approach to training in VATS lobectomy. At predefined time intervals, the surgeon
      will be called to evaluate his performance according to a number of variables
      such as the choice of VATS lobectomy indications, the number of the port used and
      length of utility incision, time spent in dissecting the hilar structures and the
      overall percentage of VATS lobectomy performed in 1 year compared to open. The
      self-assessment of the VETUS project is a unique opportunity to define the path
      of a systematic approach to training outside the traditional modalities with the
      ultimate aim of supporting quality of standardised VATS lobectomy throughout the
      country.

PMID- 29445586
TI  - Stressed Out - Therapeutic Implications of ER Stress Related Cancer Research.
AB  - The unfolded protein response (UPR) is an established and well-studied cellular
      response to the stress and serves to relieve the stress and reinstate cellular
      homeostasis. It occurs in the endoplasmic reticulum (ER), responsible of properly
      folding and processing of secretory and transmembrane proteins. It is extremely
      sensitive to alteration in homeostasis caused by various internal or external
      stressors which leads to accumulation of misfolded or unfolded proteins in the ER
      lumen. The UPR works by restoring protein homeostasis in the ER, either through
      the boosting of protein-folding and degradation capability or by assuaging the
      demands for such effects, and can cause the activation of cell death if unable to
      do so. Cancer cells have adapted to gain advantage from the UPR and keeping the
      cell away from apoptosis and promoting survival, including survival of the cancer
      stem cells and evading the immune system. Several components of the UPR are
      overexpressed in a malignant cell and are responsible for resistance from various
      chemotherapy options and radiotherapy, which are also responsible for causing ER
      stress and activating the UPR. In this review, we discuss the various ways in
      which UPR can aid different cancers to survive and evade therapy and highlight
      recent research, which exploits the UPR to confer sensitivity to these cancer
      cells against various drugs and radiation.

PMID- 29445589
TI  - Robot-assisted bronchoplasty using continuous barbed sutures.
AB  - We describe in this article our bronchoplastic robot-assisted techniques. This
      consists of using continuous barbed sutures. Our aim is to show the feasibility
      and the interest of using robotics and this kind of suture material for complex
      bronchial procedures. We report four cases in France and the UK, two wedge
      bronchoplasties and two sleeve bronchoplasties for central pulmonary tumors.

PMID- 29445590
TI  - Enhanced recovery after surgery (ERAS) and fast-track in video-assisted thoracic
      surgery (VATS) lobectomy: preoperative optimisation and care-plans.
AB  - Main specific interventions for preoperative clinical optimisation of patients
      undergoing lung cancer surgery include assessment and treatment of comorbidities,
      minimizing preoperative hospitalization, minimizing preoperative fasting, and
      optimisation of antibiotic and thrombo-embolic prophylaxis. Preoperative patient
      optimisation is considered a crucial part of enhanced recovery after thoracic
      surgery pathways. Potentially, advantages of this fast-track management could be
      even higher when considering video-assisted thoracic surgery (VATS) major lung
      resection, because reduced trauma related to minimally invasive techniques is one
      of the main factors improving postoperative outcome. Literature data and clinical
      evidences in this setting are reported and discussed.

PMID- 29445591
TI  - The time for VATS segmentectomy has come.

PMID- 29445592
TI  - Parenchymal sparing resection for carcinoid of the right main bronchus.
AB  - Surgery represents the treatment of choice for bronchial carcinoid tumors.
      Bronchoplasty for malignant and benign conditions are safe procedure but not
      often used. We present a case of carcinoid tumour of the right main bronchus
      successfully treated with parenchymal sparing resection and bronchoplasty. This
      is the preferable procedure for central typical carcinoid tumour located closed
      to the carina.

PMID- 29445593
TI  - Minimally invasive techniques in thymic surgery: a worldwide perspective.
AB  - Minimally invasive surgical techniques are important in surgical management of
      thymic pathologies. Traditional access techniques are being replaced with
      minimally invasive techniques using multiportal or uniportal approach. Adoption
      of minimally invasive techniques for thymic malignancies has been slow due to
      long term recurrence concerns. Recent studies show that minimally invasive video
      assisted thoracoscopic surgery (VATS) or robotic approach to early stage thymic
      malignancies are associated with less intraoperative bleeding, lower rate of
      respiratory complications, shorter chest tube duration and shorter hospital stay.
      Oncologic outcomes are at least equivalent to open approach. Minimally invasive
      approach for benign pathologies is widely applied. There are significant
      variations in VATS approaches for thymus, showing a multinational interest in the
      issue of minimizing trauma during thymectomy. Use of robotic technology is also
      popular, as the retrosternal area is a narrow anatomic space to manipulate
      conventional instruments. The evolution of minimally invasive surgery for thymus
      has been possible with contribution from centers all around the world. In the
      current practice, various approaches are being adopted and every surgeon should
      prefer a technique depending on surgical preference and experience.

PMID- 29445594
TI  - Thoracic endovascular aortic repair (TEVAR) versus open versus medical management
      of type B dissection.

PMID- 29445596
TI  - Minimal-invasive thoracic surgery in pediatric patients.
AB  - During the last two decades, there was a tremendous development of video-assisted
      thoracoscopic surgery (VATS), especially in the field of video-assisted lung
      resections. This article describes the actually state of this surgical technique
      in the treatment of pediatric patients. The problems in practical application are
      illustrated as well as clinical results, like they are presented in literature.

PMID- 29445595
TI  - Anesthesia and analgesia: how does the role of anesthetists changes in the ERAS
      program for VATS lobectomy.
AB  - Enhanced recovery after surgery (ERAS) programs are developed to prevent factors
      that delay postoperative recovery as well as issues that cause complications. The
      development of video-assist thoracoscopic surgery (VATS) techniques favors the
      fast recovery after thoracic procedures. ERAS strategies are based on
      multidisciplinary approach in which the anesthetist plays an important role from
      the preoperative to the postoperative phase with several goals. After
      preoperative evaluation and medical optimization, the anesthetist must ensure a
      tailored anesthetic plan aiming to a fast recovery and adequate pain relief to
      reduce the response to the surgical stress. The present narrative review presents
      the major parts of the ERAS anesthetic approach to VATS lobectomy like short
      acting drugs, protective one-lung ventilation (OLV), fluid administration and
      opioid-sparing multimodal analgesia.

PMID- 29445597
TI  - The technique of VATS right pneumonectomy.
AB  - Pneumonectomy has higher morbidity and mortality rate than any other anatomic
      lung resection. It is infrequently performed by VATS and mostly in high volume
      centers. The handling of central vessels with long instruments across very small
      incisions instead of palpation is the main cause of surgeon's discomfort and
      resistance to perform this radical type of resection. Published data on VATS
      pneumonectomy is still limited and based on case series. Nevertheless, the
      available series suggest that VATS pneumonectomy is at least equivalent to open
      pneumonectomy. Through a case presentation illustrated with surgical videos, we
      aim to describe the main technical features of a uniportal VATS right
      pneumonectomy for lung cancer. The clinical indications, contraindications,
      patient's preoperative evaluation and postoperative care will also be discussed.

PMID- 29445598
TI  - Small incisions, major complications: video-assisted thoracoscopic surgery
      management of intraoperative complications.
AB  - The object of our study is to show the causes leading to conversion, in order to
      observe the responsible variables and analyses if conversion influences the
      patient's outcome. Between January 2013 and December 2016, Udine Thoracic
      Department performed 180 video-assisted thoracoscopic surgery (VATS) lobectomies,
      and 24 cases were converted to thoracotomy due to an intra-operative complication
      such as arterial or venous bleeding, airway and other injuries. The VATS
      lobectomies' number increased over the three years: from 27 in 2013 to 55 in 2015
      and 48 in 2016. While conversion's rate decreased from 33% in 2013 to 5.5% in
      2015 and 10% in 2016. We performed a univariate and a multivariate analysis
      looking for the variables affecting the conversion rate. This was significantly
      related to intraoperative bleeding and airway injuries (P<0,001). Seventy-year
      older patients were not associated to a higher conversion rate, instead they
      showed an increased risk of post-operative complications (P<0,018, RR =1.8). We
      have focused our attention on all the variables leading to conversion and
      conditioning the patient's outcome in terms of post-operative complications and
      length of stay. The best strategy to face VATS complication is to prevent them.
      Young surgeons at the beginning of their learning curve should perform VATS
      lobectomies under close supervision of a skilled VATS surgeon. Moreover,
      conversion to open thoracotomy should be not considered a failure of VATS, but
      rather a procedure for patient's safety.

PMID- 29445599
TI  - Robotic vascular resections during Whipple procedure.
AB  - Indications for resection of pancreatic cancers have evolved to include selected
      patients with involvement of peri-pancreatic vascular structures. Open Whipple
      procedures have been the standard approach for patients requiring reconstruction
      of the portal vein (PV) or superior mesenteric vein (SMV). Recently, high-volume
      centers are performing minimally invasive Whipple procedures with portovenous
      resections. Our institution has performed seventy robotic Whipple procedures with
      concomitant vascular resections. This report outlines our technique.

PMID- 29445600
TI  - Chronic type B "residual" after type A: what I would do?
AB  - "The major goal of surgery for acute type A aortic dissection is to have an alive
      patient." This motto still remains the most important directive. However, also
      depending onto the extent of the underlying pathology and consecutively depending
      onto the extent of primary surgery, there is and will be need for additional
      classical surgical or interventional treatment sooner or later during follow-up
      in a substantial number of patients having had surgery for acute type A aortic
      dissection. This article shall guide the interested reader through the underlying
      mechanisms as well as treatment options in patients with chronic type B
      "residual" after type A repair and shall finally suggest preventive strategies to
      reduce the occurrence of this pathology to a minimum.

PMID- 29445602
TI  - Uniportal video-assisted thoracoscopic surgery (VATS) sleeve resections for non
      small cell lung cancer patients: an observational prospective study and technique
      analysis.
AB  - Bronchus sleeve resection for operative treatment of non-small cell lung cancer
      (NSCLC) is a gold standard in modern thoracic surgery in cases of centrally
      located tumors or hilar lymph node metastases. Advanced instruments and growing
      surgical experience allowed surgeons to reduce the required incisions (from 3
      port to uniportal) and to resect larger and more centrally located malignancies
      minimal invasively. It is a logical and expected advance in thoracic surgery that
      video-assisted thoracoscopic surgery (VATS) would be ultimately used also for
      complex bronchial resections. We therefore present in this study our early
      clinical results and technique of uniportal sleeve resections for patients with
      centrally located NSCLC or carcinoids. In the period 2015-2017, n:40 patients
      with NSCLC were found eligible for uniportal VATS sleeve resection in our
      institution. In two cases a thoracotomy conversion because of severe hilar scar
      tissue was necessary. In 38 cases a uniportal VATS sleeve resection could be
      completed. We believe that uniportal sleeve resections are the logical evolution
      of VATS allowing patients with locally advanced malignancies to have quicker
      recovery and reduced perioperative pain.

PMID- 29445601
TI  - Predictors of unexpected nodal upstaging in patients with cT1-3N0 non-small cell
      lung cancer (NSCLC) submitted to thoracoscopic lobectomy.
AB  - Background: In the last decades, the use of video-assisted thoracoscopic surgery
      (VATS) lobectomy for the treatment of early stage non-small cell lung cancer is
      continuously growing. This is mainly due to the development of more advanced
      surgical devices, to the rising incidence of peripheral lung tumors and is also
      favored by the increased reliability of preoperative staging techniques. Despite
      this progress, postoperative unexpected nodal upstaging is still a relevant
      issue. Aim of this study is to identify possible predictors of unexpected nodal
      upstaging in patients affected by cT1-3N0 NSCLC submitted to VATS lobectomy.
      Methods: A total of 231 cases of cT1-3N0 patients submitted to thoracoscopic
      lobectomy at our centre between June 2012 and October 2016 were retrospectively
      reviewed. All data regarding clinical staging by means of computed tomography
      (CT) and positron-emission tomography (PET)/CT were collected and reviewed. The
      subsequent pathological staging has been analyzed, with special regards to the
      possible type of nodal involvement, and the number of pathological nodal
      stations. Results: Most of the patients included in this study were in a clinical
      stage cT1aN0, cT1bN0 (stage IA) and cT2aN0 (stage IB), 86 (37.2%) patients, 73
      (31.6%) patients and 62 (26.8%) patients, respectively. Postoperative
      histopathological analysis showed that the most frequent tumor histotype was
      adenocarcinoma (192 patients, 83.1%). Thirty-eight (16.5%) patients had a nodal
      upstaging; among these, 17 (7.4%) patients had N2 disease (8 patients with
      isolated mediastinal nodal involvement, 9 patients with N1 + N2 disease) and 21
      (9.1%) patients had an isolated hilar nodal involvement (N1). At bivariate
      analysis, the clinical T (cT)-parameter (P=0.023), the histotype (P=0.029) and
      the pathological T (pT)-parameter (P=0.003) were identified as statistically
      significant predictors of nodal upstaging. Concerning the type of nodal
      upstaging, the pT was found to be statistically significant (P=0.042). At
      bivariate analysis for the number of involved nodal stations, a statistical
      significance was highlighted for the parameters cT (P=0.030) and pT (P=0.027).
      With linear logistic regression, histology as well as pT reached statistical
      significance (P=0.0275 and P=0.0382, respectively). No correlation was found
      between nodal upstaging and the intensity of FDG uptake in the primary lung tumor
      or with the timing between PET and surgery. Conclusions: There is a strong
      correlation between the clinical staging of the parameter T evaluated with CT and
      the possible unexpected nodal upstaging. The same correlation with nodal
      upstaging is found for pT. At equal clinical stage, in patients affected by
      adenocarcinoma of the lung the relative risk of having a postoperative unexpected
      nodal upstaging is almost 7 times higher than in patients with squamous cell
      carcinoma.

PMID- 29445603
TI  - Uniportal video-assisted thoracic lung segmentectomy with near
      infrared/indocyanine green intersegmental plane identification.
AB  - In the era of lung cancer screening and early detection of lung lesions,
      pulmonary segmentectomy has gained wide acceptance between thoracic community
      reducing the need of lobectomy for diagnostic purpose and treatment in case of
      centrally located benign, multiple or undetermined lesions. In rigorously
      selected patients with stage I non-small cell lung cancer (NSCLC),
      segmentectomies seem to offer similar survival outcomes rather than lobectomies,
      but associated with a better conservation of lung function. However,
      segmentectomy is a more challenging procedure to be performed compared to
      lobectomy, especially by video-assisted thoracic surgery (VATS). Many
      difficulties could arise during video-assisted segmentectomy, making the
      procedure more demanding and stressful. Following the introduction of the near
      infrared (NIR)/indocyanine imaging system on standard endoscopic module, we
      decided to adopt peripheral intravenous injection of indocyanine green (ICG) to
      identify intersegmental plain during uniportal VATS lung segmentectomy. Our
      technique herein is widely illustrated.

PMID- 29445604
TI  - Uniportal non-intubated thoracic surgery.
AB  - Uniportal video-assisted thoracoscopic surgery (VATS) is the most advanced
      evolution of the minimally invasive technique, which allows often the possibility
      to include patients in enhanced recovery programs in order to optimize the
      therapeutic pathway, shorten the length of stay and reduce hospital costs. Non
      intubated VATS procedures allow the performance of surgeries with minimal
      sedation without general anesthesia, maintaining throughout the operation
      spontaneous breathing. The principle is to create an iatrogenic spontaneous
      pneumothorax, which can provide a good lung isolation without the need of a
      double lumen tube. A survey between the members of the European Society of
      Thoracic Surgery (ESTS) showed that non-intubated VATS procedures are already
      performed by a large number of ESTS members for minor procedures. With the
      publication of new data and the spreading of uniportal VATS in many centers
      worldwide in the last decades, the application of the non-intubated technique in
      major procedure like anatomic resections is expected to grow. This technique can
      potentially be beneficial for high-risk patients but also could be used for the
      routine procedures as well, but more data are needed to establish the real
      benefit for these groups of patients.

PMID- 29445605
TI  - The state of uniportal video-assisted thoracoscopic surgery in North America: a
      survey of thoracic surgeons.
AB  - Background: In recent years, there has been an exponential growth in the research
      and development of uniportal video-assisted thoracoscopic surgery (VATS). In the
      context of the 2017 Annual Asian Single-Port VATS Symposium held in Shanghai,
      China, we sought to describe current the state of uniportal VATS in North America
      and explore factors that could influence future adoption. Methods: In March 2017,
      a five-question survey was distributed to North American Thoracic Surgeons in
      order to obtain their opinion regarding the uniportal VATS approach to pulmonary
      resection. Responses were summarized and statistical comparisons of categorical
      variables were performed using Fisher's exact test. Results: The estimated
      response rate to the survey was 16.5% (99/600). The majority of respondents were
      experienced surgeons with 41.4% (41/99) having been in practice 11-20 years. The
      majority (70%; 69/99) of surgeons had never performed a uniportal VATS procedure.
      When surgeons were asked to state what could potentially convince them to adopt
      uniportal VATS, scientific evidence of superiority (86%; 85/99) and/or of
      superior ergonomics (39%; 39/99), attendance to focused conferences with a
      practical simulation component (38%; 38/99), and the availability of surgical
      proctorship (9%; 9/99) were the most commonly selected responses. Conclusions:
      This survey is the first of its kind to provide a glimpse into the status of the
      uniportal VATS in North America. The responses suggest that there are few early
      adopters of this approach as compared to other parts of the world. The lack of
      perceived advantages to uniportal VATS and the need for more comparative evidence
      to other established approaches appear to be major obstacles to more widespread
      adoption in North America.

PMID- 29445606
TI  - Thoracoscopic Surgery in Asia.

PMID- 29445608
TI  - Robotic Surgery.

PMID- 29445607
TI  - Comprehensive evaluation of liver resection procedures: surgical mind development
      through cognitive task analysis.
AB  - Background: Liver resection is a complex procedure for trainee surgeons.
      Cognitive task analysis (CTA) facilitates understanding and decomposing tasks
      that require a great proportion of mental activity from experts. Methods: Using
      CTA and video-based coaching to compare liver resection by open and laparoscopic
      approaches, we decomposed the task of liver resection into exposure (visual field
      building), adequate tension made at the working plane (which may change three
      dimensionally during the resection process), and target processing (intervention
      strategy) that can bridge the gap from the basic surgical principle. Results: The
      key steps of highly-specialized techniques, including hanging maneuvers and
      looping of extra-hepatic hepatic veins, were shown on video by open and
      laparoscopic approaches. Conclusions: Familiarization with laparoscopic
      anatomical orientation may help surgeons already skilled at open liver resection
      transit to perform laparoscopic liver resection smoothly. Facilities at hand
      (such as patient tolerability, advanced instruments, and trained teams of
      personnel) can influence surgical decision making. Application of the rationale
      and realizing the interplay between the surgical principles and the other
      paramedical factors may help surgeons in training to understand the mental
      abstractions of experienced surgeons, to choose the most appropriate surgical
      strategy effectively at will, and to minimize the gap.

PMID- 29445609
TI  - From RATS to VATS: why we did choose this way.

PMID- 29445610
TI  - Monitored transoral endoscopic thyroidectomy via long monopolar stimulation
      probe.
AB  - This video aimed to describe the role of intraoperative neuromonitoring (IONM)
      during transoral endoscopic thyroidectomy vestibular approach (TOETVA) with
      emphasis given to IONM technical and technological notes, the identification of
      recurrent laryngeal nerve (RLN). Standardized technique of IONM consist in
      identifying and monitoring both the vagus nerve and the RLNs before and after
      resection (V1, V2, R1, R2). According to this report, IONM during TOETVA is
      feasible and safe in providing identification and function of laryngeal nerves.
      IONM enable surgeons to feel more comfortable with their initial approach to
      TOETVA or extended indications. Larger series are needed for appropriated
      evaluation of IONM in reduction of the rates for RLN complications.

PMID- 29445611
TI  - Immune response after video-assisted thoracic surgery in non-small cell lung
      cancer patients.
AB  - The effects of immunomodulation processes in patients undergoing video-assisted
      thoracic surgery (VATS) lobectomy are still debated; although, the reduced
      surgical stress of minimally invasive surgery is evident. The immunological
      repercussions could also influence the evolution of the disease and the prognosis
      of patients. The article aims to raise some points of reflection by considering
      available evidences and reiterating, once again, the prognostic utility of a
      minimally invasive procedure rather than classical approach.

PMID- 29445612
TI  - Application of the coaxial smart drain in patients with a large air leak
      following anatomic lung resection: a prospective multicenter phase II analysis of
      efficacy and safety.
AB  - Background: The presence of air leak following lung resection remains a frequent
      problem, which may prolong hospital stay and increase hospital costs. In the
      past, some studies documented the efficacy of soft and flexible chest tube in
      patients who underwent thoracic surgery. Nevertheless, safety in case of post
      operative large air or liquid leak remains questionable. The objective of this
      study was to verify through a multicentre study the safety and the effectiveness
      of the coaxial chest tube in a consecutive series of selected patients who
      underwent anatomical pulmonary resection and with an active and large air leak.
      Methods: Between October 2016 and September 2017, data from patients submitted to
      anatomical lung resection with curative intent and operated in two Department of
      Thoracic Surgery of two different were prospectively collected. The inclusion
      criteria consisted in the presence of an air leak greater than 50 mL/min measured
      with a digital drainage system during the 3 postoperative hours. A descriptive
      statistic was used to report the incidence of complications assumed to be
      associated with the use of the coaxial drain. Results: Forty-eight consecutive
      patients (27 males) submitted to lobectomy (37 patients: 77%) or anatomic
      segmentectomies (11 patients) were included in the analyses. Thirty-four
      operations (71%) were performed by video-assisted thoracic surgery (VATS). The
      median duration of chest tubes was 13 days [interquartile range (IQR), 4-19] and
      the median duration of air leak was 9 days (IQR, 2-17.5). No patient had
      undrained postoperative pleural effusion judged to require an additional chest
      tube placement. There were 12 (25%) cases of clinically or radiologically
      significant surgical emphysema; in none of these patients any additional
      procedure or re-operation was required, and they were treated conservatively by
      increasing the level of suction. Conclusions: Our experience with this novel
      Coaxial Drain was satisfactory with no clinically relevant complication caused
      using this drain, no need to insert additional drain or replace the existing one
      with another drain a duration of air leak and chest tubes as well as the
      incidence of subcutaneous emphysema that was in line with what observed in the
      daily practice in similar highly selected patients with large air leak.

PMID- 29445613
TI  - Extended uniportal bilateral sympathectomy.
AB  - Hyperhidrosis affect 3% of the population and, despite benign nature of the
      disease, the individuals seek medical advice in order to improve their quality of
      life which can be severely compromised. The interruption of the sympathetic chain
      (sympathectomy) and of the nerve of Kuntz established its role as the definitive
      treatment of primary hyperhidrosis. In this manuscript, we present our extended
      uniportal technique with the aid of the video. Uniportal approach expresses all
      its benefit when applied for this procedure because there is no specimen to be
      retrieved and all the surgery is accomplished through a 1-2 cm port access.

PMID- 29445614
TI  - Serum protein electrophoretic pattern in one-humped camels (Camelus dromedarius)
      in Tripoli, Libya.
AB  - The aim of this study was to characterize serum protein capillary electrophoretic
      pattern in apparently healthy adult male (age: 3-7 years) dromedary camels and
      also evaluate total protein and albumin levels using automated analyzer. Blood
      samples were taken from 20 camels. 5ml of blood was collected from the jugular
      vein and serum was separated from samples by centrifugation. Capillary
      electrophoresis of serum proteins identified six protein fractions in adult
      camels, including albumin, alpha1, alpha2, beta1, beta2 and gamma globulins,
      serum levels of these parameters were 3.9+/-0.04 g/dl, 0.16+/-0.01 g/dl, 0.39+/
      0.03 g/dl, 0.515+/-0.03 g/dl, 0.205+/-0.01 g/dl and 0.61+/-0.04 g/dl, and 65.42+/
      0.62 g/l, respectively. The total protein concentration was 65.42+/-0.62 g/L,
      while, the albumin/globulin (A/G) ratio was 2.4+/-0.14. The present study
      indicates six peaks with minicapillary electrophoresis and the results obtained
      were compared and interpreted in the light of finding reported by other
      investigators in camels.

PMID- 29445615
TI  - Thermodynamic effects of commercially available ice boots.
AB  - The limb of the equine athlete is subjected to all types of various stressors
      during exercise. To ensure the health of the horse and to prevent the possibility
      of lameness, it has been a common practice to apply cold therapy to the distal
      limb of the horse pre- and post-exercise. Commercially available boots are widely
      available for the application of cold therapy. To test the effectiveness of the
      boot, 6 healthy performance level sport type horses were exercised at a walk,
      trot, and canter in a round-pen and then subjected to the application of the ice
      boot for 20 minutes on a treatment leg, and no ice boot on an untreated leg.
      Thermal images were taken of the 3rd metacarpal region pre-exercise, post
      exercise, post-ice boot, and every 2 minutes after until the difference between
      the temperatures of the control leg and the treatment leg became zero. The images
      were analyzed using an analysis software (FLIR Tools) to determine the average
      temperature of the 3rd metacarpal region at each time point. The measured
      temperatures between treatments were found to be significantly different due to
      the application of the ice boot, providing evidence that the boot sufficiently
      cools the leg (P<.01). Thereafter, a 95% confidence interval was created to
      depict the average time it took for the cooled leg to return to average
      temperature post-ice boot, suggesting that it takes about 14.67 minutes for the
      difference between the temperatures of the cooled leg versus the non-cooled leg
      to become zero. This finding is significant to horse owners, trainers, and
      veterinarians that use this commonly available tool. These findings lend evidence
      to support the common practice of using cold therapy in treatment of disease in
      the horse.

PMID- 29445616
TI  - First case report of enzootic nasal adenocarcinoma in "Ouled Djellal" ewe in
      Algeria.
AB  - We report clinical and pathological features of enzootic nasal adenocarcinoma
      (ENA) in one sheep in Algeria. A one-year-old Ouled Djellal sheep from a large
      herd (~1240 animals), located in Bordj Bou Arreridj, Algeria, was clinically
      diagnosed by the presence of persistent seromucous nasal discharge, head shaking,
      muzzle licking, dyspnoea, exophthalmia and frontal protrusion. The sheep was
      euthanized, and the necropsy was performed. Gross examination showed soft touch,
      pinkish-white tumour masses in the nasal cavities with distortion of the
      turbinates and of the medium septum. According to clinical and pathological
      findings, the tumour has been defined as a low grade mixed nasal adenocarcinoma,
      with the presence of tubular and papillary structures. This is, to our knowledge,
      the first report of ENA in Algeria known to be associated with enzootic nasal
      tumour virus (ENTV) infection. However, such association requires confirmation by
      direct and/or indirect viral investigation.

PMID- 29445619
TI  - Incidence and biochemical parameters of dermatophilosis in Nigerian cattle breeds
      from livestock markets, Oyo state, Nigeria.
AB  - Dermatophilosis is one of the major economically important diseases of cattle in
      Nigeria. Managing the condition has been very challenging and re-occurrence has
      been reported with moderate to high morbidity and mortality. The incidence and
      biochemical features of cattle with dermatophilosis was conducted in June to
      December 2016 across the four geopolitical zones of Oyo state, Nigeria. Clinical
      diagnosis were made based on appearance of dermatophilosis lesion, breeds
      morphologically characterized, ageing were based on rostral dentition and
      severity based on the extent and nature of the lesion. Biochemical analysis was
      based on standard procedure as prescribed by Fortress International. Fifty cattle
      were found to be infected with clinical dermatophilosis during the period of the
      study. Twenty four (48%) in Ibadan zone, 14 (28%) in Oyo/Ogbomosho, 8 (16%) in
      Oke-ogun and 4 (8%) in Ibarapa zone. Breeds distribution across the zones showed
      28 (56%) White Fulani, 5 (10%) Sokoto Gudali, 3 (6%) Adamawa Gudali, 7 (14%) Red
      Bororo, 5 (10%) Cross breeds while the Kuri was 2 (4%). Regarding animal ages,
      less than 2 years old were 2 animals (4%) while the adults were 48 animals (96%)
      and they fall under the categories of 2-21/2 years of age, 3-31/2 years of age
      and those which are over 31/2 years of age. The different levels of severity were
      categorized into mild (20 (40%)), moderate (23 (46%)) and severe (7 (14%)) .The
      best parameters were seen in White Fulani, while the least were seen in Adamawa
      Gudali. The age group in the category of 3 - 31/2 years had most of the best
      serum values while the least values were seen in animals less than 2 years of
      age. Cattle exhibiting mild lesions had most of the best serum values and the
      least values were observed in cattle with severe lesions. No significant
      difference (p > 0.05) was observed in the mean values for the various parameters
      studied among the breeds, age, and severity of condition.

PMID- 29445617
TI  - Pathogenic Leptospira: Advances in understanding the molecular pathogenesis and
      virulence.
AB  - Leptospirosis is a common zoonotic disease has emerged as a major public health
      problem, with developing countries bearing disproportionate burdens. Although the
      diverse range of clinical manifestations of the leptospirosis in humans is widely
      documented, the mechanisms through which the pathogen causes disease remain
      undetermined. In addition, leptospirosis is a much-neglected life-threatening
      disease although it is one of the most important zoonoses occurring in a diverse
      range of epidemiological distribution. Recent advances in molecular profiling of
      pathogenic species of the genus Leptospira have improved our understanding of the
      evolutionary factors that determine virulence and mechanisms that the bacteria
      employ to survive. However, a major impediment to the formulation of intervention
      strategies has been the limited understanding of the disease determinants.
      Consequently, the association of the biological mechanisms to the pathogenesis of
      Leptospira, as well as the functions of numerous essential virulence factors
      still remain implicit. This review examines recent advances in genetic screening
      technologies, the underlying microbiological processes, the virulence factors and
      associated molecular mechanisms driving pathogenesis of Leptospira species.

PMID- 29445618
TI  - Comparative oncology: Integrating human and veterinary medicine.
AB  - Cancer constitutes the major health problem both in human and veterinary
      medicine. Comparative oncology as an integrative approach offers to learn more
      about naturally occurring cancers across different species. Canine models have
      many advantages as they experience spontaneous disease, have many genes similar
      to human genes, five to seven-fold accelerated ageing compared to humans, respond
      to treatments similarly as humans do and health care levels second only to
      humans. Also, the clinical trials in canines could generate more robust data, as
      their spontaneous nature mimics real-life situations and could be translated to
      humans.

PMID- 29445620
TI  - Genetic analysis of maternal and paternal lineages in Kabardian horses by
      uniparental molecular markers.
AB  - Studies of mitochondrial DNA (mtDNA) as well as the non-recombining part of the Y
      chromosome help to understand the origin and distribution of maternal and
      paternal lineages. The Kabardian horse from Northern Caucasia which is well-known
      for strength, stamina and endurance in distance riding has a large gap in its
      breeding documentation especially in the recent past. A 309 bp fragment of the
      mitochondrial D-loop (156 Kabardian horses) and six mutations in Y chromosome (49
      Kabardian stallions), respectively, were analyzed to get a better insight into
      breeding history, phylogenetic relationship to related breeds, maternal and
      paternal diversity and genetic structure. We found a high mitochondrial diversity
      represented by 64 D-loop haplotypes out of 14 haplogroups. The most frequent
      haplogroups were G (19.5%), L (12.3%), Q (11.7%), and B (11.0%). Although these
      four haplogroups are also frequently found in Asian riding horses (e.g. Buryat,
      Kirghiz, Mongolian, Transbaikalian, Tuvinian) the percentage of the particular
      haplogroups varies sometimes remarkable. In contrast, the obtained haplogroup
      pattern from Kabardian horse was more similar to that of breeds reared in the
      Middle East. No specific haplotype cluster was observed in the phylogenetic tree
      for Kabardian horses. On Kabardian Y chromosome, two mutations were found leading
      to three haplotypes with a percentage of 36.7% (haplotype HT1), 38.8% (haplotype
      HT2) and 24.5% (haplotype HT3), respectively. The high mitochondrial and also
      remarkable paternal diversity of the Kabardian horse is caused by its long
      history with a widely spread maternal origin and the introduction of Arabian as
      well as Thoroughbred influenced stallions for improvement. This high genetic
      diversity provides a good situation for the ongoing breed development and
      performance selection as well as avoiding inbreeding.

PMID- 29445621
TI  - Immunohistochemical evaluation of lymphocyte populations in the nictitans glands
      of normal dogs and dogs with keratoconjunctivitis sicca.
AB  - Idiopathic canine keratoconjunctivitis sicca (iKCS) is a common condition of the
      canine eye involving a deficiency in aqueous tear production which is commonly
      held to have an immune-mediated, as most probably an autoimmune
      aetiopathogenesis. Yet to date no direct evaluation has been made of the
      inflammatory cell populations in the lacrimal tissue of dogs with iKCS. Here we
      sought to quantify T and B lymphocyte populations in the lacrimal tissue of the
      nictitans glands of dogs with iKCS those with neurological KCS (nKCS)and also in
      dogs with tear production within the recognized normal levels and no ocular
      surface signs of KCS. Nictitans glands were obtained from 10 healthy dogs with no
      signs or history consistent with KCS at post-mortem or after enucleation.
      Nictitans glands were also obtained at parotid duct transposition surgery from
      ten dogs with idiopathic KCS and three with neurogenic KCS. Histological sections
      form the lacrimal tissue were processed immunohistochemically with primary
      monoclonal antibodies recognizing the T lymphocyte CD3 antigen and the B
      lymphocyte CD79a antigen. Cell numbers were counted in 10 randomly sampled
      representative high-power fields in five sections. Statistical significance of
      differences in cell numbers was determined using analysis of variance with
      significance achieved at p=0.05.Nictitans glands from dogs with iKCS showed
      elevated numbers of T and B lymphocytes compared with those from dogs with normal
      tear production. The increase in the T cell population was highly statistically
      significant (p=0.0025) while the increase in B cells, while statistically
      significant was less pronouncedly so (p=0.049). T and B lymphocyte numbers were
      not significantly elevated in nictitans glands from dogs with neurogenic KCS
      compared with those in dogs with normal tear production. The elevation in the T
      cell population seen in dogs with idiopathic KCS strongly supports the widely
      held assumption that this disease is an immune-mediated and probably autoimmune.
      The lack of increase in T cell populations in dogs with nKCS strongly suggests
      that the changes in iKCS are causing the tear deficiency and not resulting from
      it.

PMID- 29445622
TI  - Palmar annular ligament desmotomy in horses with the Arthrex-CenterlineTM : An ex
      vivo study.
AB  - The aim of this study was to evaluate the use of a single-portal endoscopic
      desmotomy of the PAL with the use of Arthrex - CenterlineTM. Ten horse distal
      front limbs from horses free of PAL disease were prepared for tenoscopy of the
      digital flexor tendon sheath (DFTS). A dual-port endoscopic desmotomy with a hook
      knife was performed in 5 specimens (Group A) and single port Arthrex-CenterlineTM
      Desmotomy was performed in another 5 specimens (Group B). The performing time,
      judgments of the surgeon, number of blade passages, and gross anatomy were
      evaluated. The performing time and surgeon judgments were significantly lower in
      Group B. No significant differences were assessed in number of passages to
      achieve a complete PAL resection and a gross anatomy evaluation. The use of
      Arthrex-CenterlineTM is feasible for a PAL desmotomy procedure. It was faster
      with more handling ease compared with the free-hand double-portal desmotomy and
      allowed the same results in terms of number of passages to complete the release
      evaluated at gross anatomy.

PMID- 29445623
TI  - Bone marrow stem cells to destroy circulating HIV: a hypothetical therapeutic
      strategy.
AB  - Human immunodeficiency virus (HIV) still poses enigmatic threats to human life.
      This virus has mastered in bypassing anti retroviral therapy leading to patients'
      death. Circulating viruses are phenomenal for the disease outcome. This
      hypothesis proposes a therapeutic strategy utilizing receptor-integrated
      hematopoietic, erythroid and red blood cells. Here, HIV specific receptors trap
      circulating viruses that enter erythrocyte cytoplasm and form inactive
      integration complex. This model depicts easy, effective removal of circulating
      HIV without any adverse effect.

PMID- 29445624
TI  - Dioxin Exposure in the Manufacture of Pesticide Production as a Risk Factor for
      Death from Prostate Cancer: A Meta-analysis.
AB  - Background: In pesticide exposure groups such as farmers, the risk of prostate
      cancer was increased, although the report of the cause of evidence is limited. We
      selected chlorophenol compounds as an important group of the contaminated
      pesticide with highly toxic 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). This
      meta-analysis, the risk of death from prostate cancer was analyzed. Methods:
      PubMed, Scopus, Scholar Google and web of Sciences until 2016 were searched. The
      standardized mortality rate (SMR) and 95% confidence intervals (CI) were obtained
      from the studies. We tested statistical heterogeneity with Cochrane Q test and I2
      index. Egger test was used for evaluating publication bias. Random or fixed
      effects models and meta-regression were also used in our analysis. Moreover,
      Cochrane tool was used to assess the risk of bias. Results: Five available papers
      consist of 28706 exposed populations were assessed. Overall standardized
      mortality rate as combined result of prostate cancer risk from the fixed model
      was 1.2 (95% confidence interval (CI) 1.02 to 1.42, P=0.027). Some biases are
      more probable in these studies such as confounding by indication, loss to follow
      up and misclassification. Conclusion: A contaminated pesticide with dioxins
      between other pesticides is an important risk factor for prostate cancers.

PMID- 29445625
TI  - Improvement of Emergency Management Mechanism of Public Health Crisis in Rural
      China: A Review Article.
AB  - Background: With the rapid development of social economy in China, various public
      health emergencies frequently occur. Such emergencies cause a serious threat to
      human health and public safety, especially in rural China. Owing to flaws in
      emergency management mechanism and policy, the government is not capable to
      effectively deal with public health emergencies. Therefore, this study aimed to
      discuss the path to improve the emergency management mechanism for public health
      emergency in rural China. Methods: This study was conducted in 2017 to detect the
      emergency management mechanism of public health crisis (EMMPHC) in Rural China.
      Data were collected using the following keywords: Rural China, public health
      emergency, emergency management mechanism, organization mechanism, operation
      mechanism in the databases of PubMed, Scopus, Web of Science, and CNKI. Results:
      EMMPHC in rural China can be enhanced from the following three aspects. First, a
      permanent institution for rural emergency management with public health
      management function is established. Second, the entire process of emergency
      management mechanism, including the stages of pre-disaster, disaster, and post
      disaster, is improved. Finally, investment in rural public health is increased,
      and an adequate reserve system for emergency resources is formed. Conclusion: The
      new path of EMMPHC in rural China can effectively help the local government
      accomplish the dispatch capability in public health emergency, and it has
      important research significance for the protection of public health and social
      stability of residents in rural China.

PMID- 29445626
TI  - Catastrophic Health Expenditure in Iran: A Review Article.
AB  - Background: One of the main challenges of healthcare systems is to protect people
      from consequences of health expenditures. Such expenditures may lead to
      catastrophic financial loss in families so that many people deny demanding
      necessary healthcare services, which results in harms to their health status. The
      aim of this systematic review was to investigate the catastrophic health
      expenditures trend and its related factors in Iran. Methods: This systematic
      review and meta-analysis was conducted on studies conducted between 1984 and
      2014. Data were collected through searching electronic databases and searching
      engines of PubMed, Scopus, EconLit, Google Scholar, Science Direct, MagIran, and
      Scientific Information Database (SID). The random effects were used with 95%
      confidence interval for the meta-analysis. Results: Out of 561 initially
      retrieved articles, finally 42 were included in the final analysis. The studies
      were conducted between 1984 and 2014. The overall proportion of exposure to
      catastrophic health expenditure in Iran was 7.5% (95% CI, 6.2 - 9.1). In the
      urban and rural areas, the proportion was 2.3% (95% CI, 1.8 - 2.9) and 3.4% (95%
      CI, 2.8 - 4.1) respectively. The overall proportion of exposure to the
      catastrophic health expenditure in hospitals was 35.9% (95% CI, 23.5 - 54.3).
      Conclusion: The catastrophic expenditures proportion of healthcare is relatively
      high in Iran and the government is expected to adopt effective measures in this
      regard, especially for the inpatient care. There are needs for special supporting
      policies for the financial protection of specific patients, the poor and
      villagers.

PMID- 29445627
TI  - Prevalence of Malocclusion in Permanent Dentition of Iranian Population: A Review
      Article.
AB  - Background: The aim of this study was systematic review and meta-analysis of
      prevalence in current and relevant literature about this developmental disorder
      to present the profile of malocclusion in Iran. Methods: This review study was
      carried out with systematically identified and critically assessed studies
      reporting malocclusion prevalence among Iranian population in permanent
      dentition. National and international databases were searched for articles about
      prevalence of malocclusion by Angle classification in different regions of Iran
      from 1994 to 2015. After applying inclusion and exclusion criteria, the quality
      of articles was checked by professional checklist. Data extraction and meta
      analysis was performed. A random-effect model was employed. Publication bias was
      checked. Results: Of 2768 articles, 21 cases were included. The pooled prevalence
      of malocclusion was about 87% (95% CI: 78.3-92.2) in Iranian population; however,
      the prevalence of malocclusion across individual studies varied considerably
      (ranging from 23.7% to 99.7%). Prevalence of normal occlusion, class I, II and
      III malocclusion were reported as 13.3% (CI 95%: 7.8-21.7), 50.7% (CI 95%: 42.9
      58.4), 21% (CI 95%: 17.5-25.1), 5.5% (CI 95%: 3-10); respectively. Maximum
      prevalence of malocclusion was in the East of Iran. Conclusion: The results
      showed a high prevalence of malocclusion in Iranian population. The baseline
      information could be appropriately utilized for the future planning to meet the
      orthodontic treatment need among the Iranian population.

PMID- 29445628
TI  - Medicinal Properties of Adiantum capillus-veneris Linn. in Traditional Medicine
      and Modern Phytotherapy: A Review Article.
AB  - Background: Adiantum capillus-veneris Linn (Maidenhair fern) is an herb belonging
      to the family Pteridaceae. It is named as "Pare-siavashan" in medical and
      pharmaceutical textbooks of Iranian Traditional Medicine. The fronds of
      Maidenhair fern were mainly administrated by ancient physicians as single
      medicine or in combination with other plants in multi-herbal formulations for
      curing different diseases. Because of different chemical compositions, the herb
      fronds were also assessed for its numerous pharmacological effects. Therefore,
      the current study was done to review the traditional usage and modern
      pharmacological and toxicological effects of Maidenhair fern. Methods: Scientific
      databases and publications including Web of Science, PubMed, Scopus, Science
      direct, Cochrane Library, SID (for Persian papers) and medical and pharmaceutical
      textbooks of traditional medicine as well were searched for "Adiantum capillus
      veneris", "Maidenhair fern" and "Pare-siavashan" without limitation up to 2016.
      Results: Maidenhair fern exhibited to possess anti-diabetic, anticonvulsant,
      analgesic, hypocholesterolemic, goitrogenic, anti-thyroidal, antibacterial,
      antifungal, wound healing, antiobesity, anti hair loss, anti-asthmatic, anti
      inflammatory, antidiarrheal and antispasmodic, antioxidant as well as diuretic,
      anti-urolithiatic and detoxifying effects in modern medicine. Ancient physicians
      declared some of the confirmed pharmacological effects. Conclusion: Maidenhair
      fern frond can be a good candidate for clinical purpose. Therefore, future
      researches on the other mentioned effects in traditional medicine are
      recommended.

PMID- 29445629
TI  - Trends and Associated Factors of Hypertension among Residents Aged >=15 Years in
      Guangzhou, China, 2004-2013.
AB  - Background: We aimed to describe the trends and associated factors of
      hypertension among residents aged >=15 yr in Guangzhou, China. Methods: Three
      standardized cross-sectional health surveys were conducted in 2004, 2009 and 2013
      using a multi-stage cluster sampling method, and a total of 69128 qualified
      participants were included in the study. The data were obtained through physical
      health examination and questionnaire survey. Results: The age-standardised
      prevalence of hypertension increased from 12.5% to 16.0% between 2004 and 2009
      and declined from 16.0% to 14.0% between 2009 and 2013, and crude prevalence
      respectively was 14.6%, 19.1% and 18.8% in 2004, 2009 and 2013. The proportion of
      optimal blood pressure dropped from 51.1% to 33.2%, high-normal blood pressure
      increased from 20.1% to 28.9%, grade 1 hypertension and grade 2 or 3 hypertension
      increased from 11.5% to 13.6% and 3.9% to 5.8% between 2004 and 2013. The average
      age was significantly increased (P<0.001) from 42.8 to 47.5 yr, and the average
      body mass index slightly increased (P<0.001) from 22.4 to 23.0. Logistic
      regression analysis shows that higher age, male, higher body mass index, smoking
      and drinking alcohol were potential risk factors for hypertension. Conclusion:
      Both crude and age-standardized prevalence of hypertension were initially
      increased, but subsequently decreased in Guangzhou during 2004-2013. The optimal
      blood pressure population decreased significantly while the high-normal blood
      pressure population increased substantially during the survey period.

PMID- 29445631
TI  - Effects of Negative Emotions and Life Events on Women's Missed Miscarriage.
AB  - Background: To investigate the effects of negative emotions and life events on
      women's missed miscarriage. Methods: Overall, 214 women diagnosed with a missed
      miscarriage by prenatal examination from 2016-2017 in Xiamen Maternal and Child
      Health Care Hospital, Xiamen, China were selected as the observation group
      compared to 214 women as control group. The general data of the patients were
      investigated by self-programmed questionnaires. Zung Self-Rating Anxiety Scale,
      Center Epidemiological Studies Depression Scale; Life Events Scale for Pregnant
      Women were used conduct the study. General data, anxiety, depression and life
      events were compared between the two groups of patients, and statistically
      different factors were included in the multivariate Logistic regression analysis.
      Results: There were statistically significant differences in the educational
      level, pre-pregnancy health status, planned pregnancy, pre-pregnancy or
      gestational gynecological inflammation and the initiative to obtain knowledge of
      prenatal and postnatal care between the two groups of pregnant women (P<0.01);
      there were also statistically significant differences in score of life events,
      score of anxiety and score of depression between them (P<0.01). The high
      educational level, good health status before pregnancy and the initiative to
      obtain the knowledge of prenatal and postnatal care were taken as the independent
      protective factors for the missed miscarriage in pregnant women, while life
      events, anxiety and depression were independent risk factors for it. Conclusion:
      Negative emotions and life events increase the risk of women's missed
      miscarriage, and the high educational level, good health status before pregnancy
      and the initiative to obtain the knowledge of prenatal and postnatal care reduce
      the risk of women's missed miscarriage.

PMID- 29445630
TI  - Effects of First Diagnosed Diabetes Mellitus on Medical Visits and Medication
      Adherence in Korea.
AB  - Background: The National Health Insurance Service (NHIS) conducted a screening
      test to detect chronic diseases such as hypertension and diabetes in Korea. This
      study evaluated the effects of health screening for DM on pharmacological
      treatment. Methods: The data from qualification and the General Health Screening
      in 2012, the insurance claims of medical institutions from Jan 2009 to Dec 2014,
      and the diabetic case management program extracted from the NHIS administrative
      system were used. Total 16068 subjects were included. Visiting rate to medical
      institution, medication possession ratio and the rate of medication adherence of
      study subjects were used as the indices. Results: The visiting rates to medical
      institutions were 39.7%. The percentage who received a prescription for a
      diabetes mellitus medication from a doctor was 80.9%, the medication possession
      ratio was 70.8%, and the rate of medication adherence was 57.8%. Conclusion: The
      visiting rate, medication possession ratio and rate of medication adherence for
      DM medication were not high. In order to increase the visiting rate, medication
      possession ratio and rate of medication adherence, NHIS should support
      environment in which medical institutions and DM patients can do the role of each
      part.

PMID- 29445632
TI  - Trend of Medical Tourism Publications: An Attempt to Explore the Involved
      Academic Disciplines and Interests.
AB  - Background: Medical tourism suffers from the lack of a consensus regarding the
      involved categories. This study aimed to address this gap from the academic
      disciplines and publications perspective. Methods: Totally 1954 citations were
      identified through a formula of keyword search of SCOPUS. In order to classify
      the various subject areas, we followed the international standard classification
      of education (ISCED) developed by UNESCO. Moreover, the trends of publications
      were identified based on their popularity between 2000 and 2017. Results: The
      category with the most interests on publication about medical tourism was 'health
      and welfare', followed by 'social science'. Even though various disciplines were
      involved in the medical tourism, it seems that a downward trend has been
      experienced since 2015. Conclusion: The identified key trends of medical tourism
      publications will benefit researchers exploring the categories of medical tourism
      or health travel. The results contribute to advance the state of knowledge from
      the academic perspective.

PMID- 29445633
TI  - The Effect of Intensive Statin Therapy on Symptomatic Intracranial Arterial
      Stenosis.
AB  - Background: The aim of this study was to observe the effect of intensive statin
      therapy on symptomatic intracranial arterial stenosis. Methods: overall, 120
      patients with symptomatic intracranial arterial stenosis were admitted to the
      Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China
      from January 2010 to May 2013. They were randomly divided into three groups and
      were given different doses of atorvastatin orally for 1 year or more, and
      followed up for 12 months. The three groups were assessed for clinical end-point
      event rates and changes in cerebral blood flow value before and after treatment
      to assess the effectiveness of intensive statin therapy. Results: The incidence
      rates of end-point cerebrovascular events in the low-dose group (10 mg/d), the
      general-dose group (20 mg/d) and the intensive treatment group (40 mg/d) were
      26.3%, 13.5% and 5.4% respectively during the 12-month follow-up after treatment.
      There was a significant difference between the low dose group and the intensive
      treatment group (P<0.05). The relative cerebral blood flow and relative cerebral
      blood volume of the three groups were significantly higher than those before
      treatment (P<0.05), and the relative time to peak for the intensive treatment
      group was shorter than that before treatment (P<0.001). Conclusion: Atorvastatin
      at 40 mg/d has a significant advantage compared with atorvastatin at 20 mg/d and
      10 mg/d in reducing cerebrovascular events and improving cerebral blood flow.

PMID- 29445635
TI  - Implementing Health Impact Assessment at National Level: An Experience in Iran.
AB  - Background: According to the general health policies issued in 2014, Health
      Impact Assessment (HIA) or Health Annex should be implemented in Iran. The
      present study provided a model for executing HIA in the Iranian context as a
      developing country. Methods: This is a system design study with the qualitative
      approach. The data on the system components were gathered via reviews of the
      literature, in-depth interviews and focused group discussions (FGDs) with
      experts. The information were contently analyzed in order to draft the model and
      a consensus was reached on by the steering committee. Results: Fifteen in-depth
      interviews and six FGD meeting were conducted. The equity-based approach in
      assessing the health impacts of policies, programs and projects were chosen as
      the most practical tool. Experts believe that for the next five years, HIA should
      be used just for the "national projects" so that the ministries and national
      agencies could be empowered. Components of the model including structure,
      procedures, and standards, management style, mission and resources were prepared.
      The national regulations and protocols were sent to the SCHFS Secretariat for
      final revision and the council approval. Conclusion: The hasty implementation of
      HIA will face serious resistances as the health-oriented attitude and behavior in
      both government and non-governmental sectors will gradually form. Also, the
      overlapping of the contents of HIA with other tools such as Environmental,
      Cultural and Social Impact Assessments, currently used by other sectors, causes
      difficulties in implementing the HIA by the Ministry of Health and Medical
      Education.

PMID- 29445634
TI  - Evaluation of Respiratory Symptoms among Workers in an Automobile Manufacturing
      Factory, Iran.
AB  - Background: This study estimated the prevalence of respiratory symptoms and
      disorders among workers exposed to exposure to volatile organic compound (VOCs)
      in an automobile manufacturing factory in Tehran, Iran in 2016. Methods: Subjects
      of this case-control research were included 80 samples including 40 workers
      exposed to different level of BTEX as well as 40 unexposed individuals were
      considered as control group. Methods 1501 and 7602 presented by the National
      Institute of Occupational Safety and Health (NIOSH) were used for the sampling
      and analysis of compounds in the air. Gas Chromatography-Flame Ionization
      Detector (GC-FID) was used for analysis of compounds of interest. Six silica
      samples were collected during the campaign. Silica analyses were performed by
      using visible absorption spectrophotometry system. Lung functions were evaluated
      for 80 workers (40 exposed, 40 nonexposed) using spirometry system. Results: The
      average amount of total dust and free silica measured in factory were 7.3+/-1.04
      mg.m-3 and 0.017+/-0.02 mg.m-3 respectively. Average benzene, toluene, ethyl
      benzene and xylene exposure levels in exposed subject's median were 0.775+/-0.12,
      1.2+/-2.08, 45.8+/-8.5, and 42.5+/-23.9 ppm respectively. Statistical tests
      showed significant difference between pulmonary function tests (except PEF) of
      exposed and non-exposed individuals before and after employment (P<0.05). Workers
      exposed to VOCs presented lower levels of FVC, VC, and PEF than the control group
      except FEV1/FVC%, FEV1, FEF2575 and FEV1/VC%. Conclusion: Decline in lung volumes
      and respiratory symptoms, significant difference associated with the exposure to
      dust or gas, duration of exposure, and smoking habit. Therefore, lung function
      tests should be performed before and after the employment to identify sensitive
      workers candidates.

PMID- 29445636
TI  - Economic Burden of Pediatric Asthma: Annual Cost of Disease in Iran.
AB  - Background: Asthma is the first cause of children hospitalization and need for
      emergency and impose high economic burden on the families and governments. We
      aimed to investigate the economic burden of pediatric asthma and its contribution
      to family health budget in Iran. Methods: Overall, 283 pediatric asthmatic
      patients, who referred to two tertiary pediatric referral centers in Tehran
      capital of Iran, included from 2010-2012. Direct and indirect asthma-related
      costs were recorded during one-year period. Data were statistically analyzed for
      finding association between the costs and factors that affect this cost
      (demographic variables, tobacco smoke exposure, control status of asthma and
      asthma concomitant diseases). Results: Ninety-two (32.5%) females and 191(67.5%)
      males with the age range of 1-16 yr old were included. We found the annual total
      pediatrics asthma related costs were 367.97+/-23.06 USD. The highest cost
      belonged to the medications (69%) and the lowest one to the emergency (2%). We
      noticed a significant increasing in boys' total costs (P=0.011), and 7-11 yr old
      age group (P=0.018). In addition, we found significant association between total
      asthma costs and asthma control status (P=0.011). Conclusion: The presence of an
      asthmatic child can consume nearly half of the health budget of a family. Our
      results emphasis on improving asthma management programs, which leads to
      successful control status of the disease and reduction in economic burden of
      pediatric asthma.

PMID- 29445637
TI  - Virulence Determinants and Antimicrobial Resistance Patterns of Vancomycin
      resistant Enterococcus faecium Isolated from Different Sources in Southwest Iran.
AB  - Background: This study aimed to investigate the incidence of antibiotic
      resistance and virulence genes in vancomycin-resistant Enterococcus faecium
      isolated from different sources in southwest Iran from Mar to Sep 2015. Methods:
      Overall, 120 E. faecium isolates (80 VRE and 40 vancomycin-susceptible
      enterococci [VSE] isolates) were obtained from four hospitals. The resistance of
      the VRE isolates was determined by disk diffusion method. Multiplex PCR was
      performed to detect the virulence genes carried by the E. faecium isolates,
      namely, enterococcal surface protein (esp), hyaluronidase (hyl), and collagen
      binding adhesin (acm). Results: All the VRE isolates exhibited multidrug
      resistance, with the rates of resistance to ampicillin, erythromycin, and
      ciprofloxacin reaching high levels. The isolates were least resistant to
      chloramphenicol and nitrofurantoin, but all of them were susceptible to
      linezolid. 46.6%, 20.8%, and 86.6% of the E.faecium isolates carried the esp,
      hyl, and acm genes, respectively. Conclusion: There is a significant difference
      between the prevalence of esp and hyl genes in the VRE and VSE isolates. In the
      VRE isolates, the high prevalence of multidrug resistance were found and the
      difference in the prevalence of esp among various sources was significant. The
      findings reflected a relationship between the prevalence of esp and hyl and
      resistance to certain antibiotics.

PMID- 29445638
TI  - Comparison Characteristics of Family and Demographic of Children with Antenatal
      Hydronephrosis between 2nd and 3rd Trimesters of Gestation.
AB  - Background: The aim of this study was comparison characteristics of family and
      demographics of children with antenatal hydronephrosis, in 2nd and 3rd trimester
      of pregnancy, in order to the need for postnatal management. Methods: This cross
      sectional study described some information from family of children with antenatal
      hydronephrosis, at the Pediatric Urology Research Center of Children's Hospital
      Medical Center of Tehran University of Medical Sciences. Data for 193 children,
      admitted in 2012-2013, were collected retrospectively. They were allocated to two
      groups of 2nd and 3rd trimester, based on the time of diagnosis antenatal
      hydronephrosis. Data analysis was done using SPSS. Chi-Square, Fisher-exact and
      independent t-test also Mantel-Hanzel test were used. P-value<0.05 was considered
      as statistically significant. Results: Of 193 infants (36 female, 157male), the
      antenatal hydronephrosis of 76 cases (39.4%) have been diagnosed in the 2nd
      trimester. In addition, 110 cases (57%) were bilateral and 33 cases (17.1%) had
      severe antenatal hydronephrosis. Consanguinity marriage, being unilateral or
      bilateral and the severity of antenatal hydronephrosis were significant with the
      specific trimester that it has been diagnosed (P<0.05). Conclusion: Infants with
      bilateral and severe grade of antenatal hydronephrosis also with the history of
      consanguinity marriage among their parent will diagnose in the second trimester
      more than the third trimester and will refer for some surgical correction,
      relating to other kidney diseases such as vesicoureteral reflux, more than
      others. Thus, this is a good sign for caring infants.

PMID- 29445639
TI  - The Association between Adverse Events in the Last 5 Years and the Rate of Breast
      Cancer.
AB  - Background: This study was conducted in Yazd Province, Central Iran aimed to
      investigate the relationship between adverse events and breast cancer during 2012
      2014. Methods: Hospital-based case-control study of 150 women with breast cancer
      and 150 healthy women (did not have breast cancer) was conducted. Sampling was
      performed in the form of accessibility. Data collection was conducted using
      questionnaire through interview. The collected data were entered into SPSS for
      statistical analysis. Results: The mean age of participants was 51.58 yr. Eight
      percent of cases and 1.3% of the controls had experienced the sister's death over
      the past 5 yr, this difference was statistically significant (P=0.03). Factors
      such as disability due to illness, divorce, unemployment, the second marriage,
      addiction, ill spouse, child's problems (such as conflict, unemployment,
      addiction, legal troubles, illness), taking care of their own parents or their
      husband's parents, migration, change of habitat, loss of home, communication
      problems, job-relevant factors were not significantly different between the two
      groups (P>0.05). Mean of severity of adverse events in both groups was
      significantly different (8.92+/-8.29 in the case group, 5.72+/-5.6 in the control
      group) (P=0.000). Conclusion: There was no significant relationship between
      adverse events in the last 5 yr and the risk of breast cancer. Factors such as
      personality and ability to cope with problems may positively influence this
      relationship.

PMID- 29445640
TI  - Medical Waste Management in Community Health Centers.
AB  - Background: Non-standard management of medical waste leads to irreparable side
      effects. This issue is of double importance in health care centers in a city
      which are the most extensive system for providing Primary Health Care (PHC)
      across Iran cities. This study investigated the medical waste management
      standards observation in Tabriz community health care centers, northwestern Iran.
      Methods: In this triangulated cross-sectional study (qualitative-quantitative),
      data collecting tool was a valid checklist of waste management process developed
      based on Iranian medical waste management standards. The data were collected in
      2015 through process observation and interviews with the health center's staff.
      Results: The average rate of waste management standards observance in Tabriz
      community health centers, Tabriz, Iran was 29.8%. This case was 22.8% in
      dimension of management and training, 27.3% in separating and collecting, 31.2%
      in transport and temporary storage, and 42.9% in sterilization and disposal. Lack
      of principal separation of wastes, inappropriate collecting and disposal cycle of
      waste and disregarding safety tips (fertilizer device performance monitoring,
      microbial cultures and so on) were among the observed defects in health care
      centers supported by quantitative data. Conclusion: Medical waste management was
      not in a desirable situation in Tabriz community health centers. The expansion of
      community health centers in different regions and non-observance of standards
      could predispose to incidence the risks resulted from medical wastes. So it is
      necessary to adopt appropriate policies to promote waste management situation.

PMID- 29445641
TI  - Effects of the Tui-na and Thai Massage Techniques on Vascular Arterial Compliance
      in Middle-aged Korean Men.

PMID- 29445642
TI  - A Rare Case of Foreign Body in Stomach: Dental Mouth Mirror.

PMID- 29445643
TI  - Influenza Vaccination in Identified People Living with HIV/AIDS and Health Care
      Providers of Triangular Clinics in Iran, 2015-2016.

PMID- 29445644
TI  - The Prevalence of Vitamin D Deficiency in Adults in Kermanshah, Western Iran.

PMID- 29445645
TI  - Evaluating the Effect of Using Training CDs on the Patients with Type II
      Diabetes.

PMID- 29445646
TI  - A Comprehensive Decision Support System for Pediatrics Immunization.

PMID- 29445647
TI  - Re-emerging Tularemia in Some Middle East Countries: What Are the Reasons?

PMID- 29445648
TI  - Importance of Prevention and Control of Nosocomial Infections in Iran.

PMID- 29445649
TI  - Analytical Report on the Output of "Iranian Journal of Public Health" During 2014
      2017.

PMID- 29445651
TI  - Cost-effectiveness of laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y
      gastric bypass in two hospitals of Tehran city in 2014.
AB  - : Background: Bariatric surgery with the improvement of obesity-related diseases,
      increases longevity and quality of life and is more cost-effective when compared
      to non-surgical Procedures. Objective: The aim of this study is to compare the
      cost-effectiveness of Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Roux
      en-Y Gastric Bypass (LRYGB). METHOD: This study was performed in two stages.
      Initially, a cross-sectional study was carried out for costing LSG and LRYGB in
      Rasoul Akram and Bahman hospitals in Tehran in the year 2014. Direct costs for
      each surgical procedure were calculated according to the average time of surgery
      in both the private and public sectors. In the second stage, using Outcome
      (DeltaBMI) collected by means of a systematic review study and cost data; cost
      effectiveness of two surgical procedures was examined by ICER analysis and
      compared with threshold limit. The Perspective of this analysis was health
      system. Results: The direct cost of services for LRYGB was $ 2991.5 (98121659
      Rials) in the public sector and $4221.9 in the private sector. In LSG, it was $
      1952.9 (64055468 R) in the public sector and $ 3177.2 in the private sector. ICER
      for LSG was 720.48(23631855 R) and $716.27 (23493924 R) in private and public
      sector respectively. Conclusion: In this study, LSG procedure when compared to
      LRYGB was cost effective. The ICER obtained indicated that LSG surgery in
      comparison to LRYGB was $716.27 (23493924 R) and $720.48(23631855 R) in the
      public and private sector respectively. Moreover, per unit change in BMI was less
      than the threshold.

PMID- 29445650
TI  - The relationship between social capital components and control of type 2
      diabetes: A path analysis model.
AB  - Background: Social capital is an important interpersonal organizational resource
      that may affect health behaviors and seems to be an important factor in chronic
      diseases. Considering the lack of evidence on this topic, in the present study,
      we aimed at investigating the association between components of social capital,
      socioeconomic condition, and controlling Type 2 diabetes mellitus in Iran.
      Methods: This study was conducted on 300 patients with Type 2 diabetes in Tehran,
      Iran. In this study, simple random sampling method was used for data collection.
      Path analysis model was used to examine the potential association between social
      capital components and to determine the factors that control Type 2 diabetes.
      Results: In the present study, most of the participants were female (70.7%) and
      married (78.7%). Path coefficients were calculated by a series of multiple
      regression analyses based on the conceptual model. The final model had a proper
      fit with Chi-square = 2.08 (DF = 1, P = 0.049), GFI = 0.542, AGFI = 0.915, NFI =
      0.228, RFI = 0.284, IFI = 0.299, TLI = 0.292, CFI = 0.219, and RMSEA = 0.033. The
      Groups and networks (network) (beta = 0.051, p = 0.036) and trust and solidarity
      (beta = -0.018, p = 0.028) had a direct positive and negative effect on HbA1C,
      respectively. The results also revealed that education levels had a direct
      positive effect on groups and networks (network) (beta = 0.118, p = 0.036), trust
      and solidarity (beta = 0.082, p = 0.007), information and communication (beta =
      0.037, p = 0.027), and contribution in team works and public activities (beta =
      0.064, p = 0.003). In addition, education levels had an indirect positive effect
      on HbA1C through their effect on groups and networks (network), trust and
      solidarity, and information and communication. Conclusion: Social capital has a
      significant relationship with diabetes. Although it was not specified clearly
      which components of social capital were associated with diabetes, trust and
      solidarity showed a negative direct effect on HbA1C, respectively. Therefore,
      developing and implementing local and collective programs to build trust and
      increase the standards of social trust in patients with diabetes can be effective
      in controlling HbA1C.

PMID- 29445652
TI  - Pattern of some risk factors of cardiovascular diseases and liver enzymes among
      Iranian seafarers.
AB  - Background: Little information is available on the trend in cardiovascular risk
      factors and hepatic enzymes in Iranian seafarers. The present study aimed at
      assessing the pattern of obesity, hypertension, diabetes, elevated serum glutamic
      oxaloacetate transaminase (SGOT), and serum glutamate pyruvate transaminase
      (SGPT) in Iranian seafarers during 2010 to 2014. Methods: Data on cardiovascular
      risk factors and hepatic enzymes were extracted from seafarers' annual health
      examination of National Iranian Tanker Company (NITC) of 2010, 2012, and 2014.
      The repeated measure ANOVA was used to compare continuous variables across 3
      years. Categorical data were analyzed using Chi-square test. Over weight was
      defined as BMI (Body Mass Index) >25 kg/m2; obesity was defined as BMI>=30 kg/m2;
      hypertension was defined as systolic blood pressure (SBP)> 140 mmHg, and
      diastolic blood pressure (DBP)> 90 mmHg, or a history of antihypertensive drug
      use. Diabetes (DM) was defined as fasting blood sugar (FBS) > 110 mg/dl, or
      having a history of oral hypoglycemic agents; and elevated SGOT and SGPT were
      defined as SGOT > 40 U/L and SGPT > 40 U/L, respectively. Results: The BMI mean+/
      SD values of Iranian seafarers were 24.81+/-3.07 kg/m2, 25.51+/-2.96 kg/m2, and
      25.96 +/- 3.02 kg/m2 in 2010, 2012, and 2014, respectively. A significant
      difference was observed in BMI over the study period. The mean of systolic and
      diastolic blood pressure did not significantly increase over time. The SGOT and
      SGPT means were not significantly different from 2010 to 2014. The prevalence of
      overweight increased significantly from 46.7% to 60.9% over the study period;
      however, the prevalence of obesity, hypertension, elevated SGOT, and elevated
      SGPT did not change significantly. Conclusion: The current survey showed that the
      obesity problem has increased among Iranian seafarers working on tankers, which
      is a concerning problem because obesity has negative effects on seafarers'
      health.

PMID- 29445653
TI  - Elements of healthy death: a thematic analysis.
AB  - Background: Death is a natural and frightening phenomenon, which is inevitable.
      Previous studies on death, which presented a negative and tedious image of this
      process, are now being revised and directed towards acceptable death and good
      death. One of the proposed terms about death and dying is "healthy death", which
      encourages dealing with death positively and leading a lively and happy life
      until the last moment. This study aimed to explain the views of Iranians about
      the elements of healthy death. Methods: This qualitative study was conducted for
      12 months in two general hospitals in Tehran (capital of Iran), using the
      thematic analysis method. After conducting 23 in-depth interviews with 21
      participants, transcription of content, and data immersion and analysis, themes,
      as the smallest meaningful units were extracted, encoded and classified. Results:
      One main category of healthy death with 10 subthemes, including dying at the
      right time, dying without hassle, dying without cost, dying without dependency
      and control, peaceful death, not having difficulty at dying, not dying alone and
      dying at home, inspired death, preplanned death, and presence of a clergyman or a
      priest, were extracted as the elements of healthy death from the perspective of
      the participants in this study. Conclusion: The study findings well explained the
      elements of healthy death. Paying attention to the conditions and factors causing
      healthy death by professionals and providing and facilitating quality services
      for patients in the end stage of life make it possible for patients to experience
      a healthy death.

PMID- 29445654
TI  - Subgroup dairy products consumption on the risk of stroke and CHD: A systematic
      review and meta-analysis.
AB  - Background: There is no global consensus about the relationship between dairy
      consumption and cardiovascular diseases (CVD). This study aimed at integrating
      the results of several studies to predict the dairy effects on CVD, e.g. stroke
      and CHD. Methods: In the present study, some major databases such as Scopus,
      Science Direct, and PubMed were searched up to September 2014. All prospective
      cohort studies dealing with dairy products consumption and CVD were surveyed
      regardless of their publication date or language. This reference population
      includes all individuals without any delimitation with regard to age, gender, or
      race. The quality of the study was evaluated using STROBE Checklist. Study
      selection and data extraction were done by 2 independent researchers separately.
      The indices in this study were RR and HR. The random model was used to combine
      the results. Results: Out of 6234 articles, 11 were included in the meta
      analysis. No relationship was found between stroke and consumption of milk,
      cream, and butter, and the results are as follow: RR = 0.91 (95%CI: 0.81-1.01)
      for milk, RR = 0.97 (95%CI: 0.88-1.06) for cream, and RR = 0.95 (95%CI: 0.85
      1.07) for butter. However, cheese was found to decrease stroke risk: RR = 0.93
      (95%CI: 0.88-0.99). The relationship of CHD with consumption of milk, cheese,
      cream, and butter are as follows, respectively: RR = 1.05 (95% CI: 0.96- 1.15),
      RR = 0.90 (95%CI: 0.81-1.01), RR = 0.96 (95% CI: 0.87-1.06), and RR = 0.99
      (95%CI: 0.89-1.11). In other words, no relationship existed between dairy
      products and CHD. Conclusion: No relationship was found between consumption of
      various dairy products and CHD or stroke, except for cheese that decreased stroke
      risk by 7%. Considering the small number of studies, the result of the present
      study is not generalizable and more studies need to be conducted.

PMID- 29445655
TI  - A RCT comparing lumbosacral orthosis to routine physical therapy on postural
      stability in patients with chronic low back pain.
AB  - Background: Poor balance performance and impaired postural control have been
      frequently reported in patients with low back pain. However, postural control is
      rarely monitored during the course of treatment even though poor postural control
      may contribute to chronicity and recurrence of symptoms. Therefore, the present
      study aimed at investigating the effect of a nonextensible lumbosacral orthosis
      (LSO) versus routine physical therapy on postural stability of patients with
      nonspecific chronic low back pain. Methods: This was a randomized controlled
      trial conducted between November 2015 and May 2016 at the outpatient physical
      therapy clinic of the School of Rehabilitation Sciences. Patients with
      nonspecific chronic low back pain aged 20 to 55 years were randomly allocated to
      the intervention and control groups. Both groups received 8 sessions of physical
      therapy twice weekly for 4 weeks. The intervention group received nonextensible
      LSO in addition to routine physical therapy. Pain intensity, functional
      disability, fear of movement/ (re)injury, and postural stability in 3 levels of
      postural difficulty were measured before and after 4 weeks of intervention. A
      2*2*3 mixed model of analysis of variance (ANOVA) was used to determine the main
      and interactive effects of the 3 factors including group, time, and postural
      difficulty conditions for each variable of postural stability. Results: The LSO
      and control groups displayed significant improvement in postural stability at the
      most difficult postural task conditions (P-value for 95% area ellipse was 0.003;
      and for phase plane, the mean total velocity and standard deviation of velocity
      was <0.001). Both groups exhibited a decrease in pain intensity, Oswestry
      Disability Index, and Tampa Scale of Kinesiophobia after 4 weeks of intervention.
      A significant difference between groups was found only for functional disability,
      with greater improvement in the orthosis group (t = 3.60, P<0.001). Conclusion:
      Both routine physical therapy and LSO significantly improved clinical and
      postural stability outcomes immediately after 4 weeks of intervention. The
      orthosis group did not display superior outcomes, except for functional
      disability.

PMID- 29445656
TI  - Epidemiological and clinical characteristics of scorpionism in Shiraz (2012
      2016); development of a clinical severity grading for Iranian scorpion
      envenomation.
AB  - Background: Scorpionism is a public health problem in some provinces in Iran. The
      present study aimed to assess the clinical manifestations of scorpion
      envenomation in Shiraz and determine a clinical severity grading for Iranian
      scorpion envenomation in order to suggest a treatment guideline for emergency
      physicians. Methods: In this analytic retrospective study, all medical charts of
      patients with scorpion sting admitted in the adult medical toxicology center in
      Shiraz during July 2012 to July 2016 were assessed. Data regarding the patient's
      age, gender, sting site, month of envenomation, time of sting, clinical
      manifestations, vital signs, presence of blood or hemoglobin in urine analysis,
      duration of admission, color of scorpion, received treatments, and administration
      of scorpion antivenin were recorded. Results: The scorpions in Shiraz and its
      suburban area were classified into two groups: yellow scorpions ( Mesobuthus
      eupeus, Mesobuthus caucasicus , and Compsobuthus matthiesseni) and Hottentotta
      scorpions (Hottentotta jayakari and Hottentotta zagrosensis). A total of 126
      cases of scorpion stings were assessed. About 59% (n=74) were males. The patients
      aged 8-63 years (mean age, 33.8+/-11.5 years). About 38.4% (n=48) of the stings
      occurred during summer. More than 40% of patients (n=51) referred to the
      emergency department (ED) at night. Localized pain was the most frequent
      presenting complaint (76.2%). The most frequent general symptom was nausea
      (6.3%). The most prevalent envenomation site was the lower extremities followed
      by upper extremities (43.5% and 41.9%, respectively). Based on the clinical
      severity grading for Iranian scorpion envenomation, 65, 43, and 18 patients
      (51.6%, 34.1%, and 14.3%) were classified in the grades I, II, and III,
      respectively. Eighty-one (73%) patients stayed in the ED from 1 to 6 hours, and
      30 (27%) patients stayed for >6 hours for observation. Severe localized pain was
      more prevalent in stings with Hottentotta scorpions than yellow scorpions
      (P=0.01). The season of envenomation with Hottentotta scorpions was summer in all
      cases, but envenomation with yellow scorpions was seen throughout the year. All
      patients received symptomatic treatment, and five were given scorpion antivenin.
      No death was reported. Conclusion:Hottentotta jayakari is recommended to be
      listed among the medically important scorpions in Iran. Moreover, scorpion-stung
      patients in geographical regions where Hemiscorpius lepturus and Androctonus
      crassicauda are not prevalent may be treated in outpatient departments. The
      presented grading system can be used for treating patients with scorpion
      envenomation.

PMID- 29445657
TI  - Correlation of visfatin level with non-alcoholic fatty liver in metabolic
      syndrome.
AB  - Background: Metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD)
      is a common public health problem. Visfatin is secreted by visceral adipose
      tissue and is an adipocytokine. It could be a pro-inflammatory adipocytokine and
      is related to the metabolic syndrome and non-alcoholic fatty liver disease. This
      study evaluated the association between visfatin levels in patients with the
      metabolic syndrome with and without non-alcoholic fatty liver disease (NAFLD).
      Methods: In this cross-sectional study, 120 patients with metabolic syndrome were
      selected. They were categorized into two groups, patients with fatty liver (n=70)
      and without fatty liver disease (n=50). Laboratory and anthropometric options
      such as age, sex, systolic blood pressure, fasting blood sugar, lipid profile,
      liver enzymes, uric acid, visfatin, insulin, BMI, waist circumference, and TNF
      alpha were measured. The chi-square test, Mann-Whitney, t test, Spearman and
      Pearson correlations were used for the data analysis. Results: There was a
      significant difference between the fatty liver and non-fatty liver disease with
      visfatin, BMI, FBS and lipid profile (p<0.05). The mean+/-SD level of visfatin
      was 37.1+/-1.7 ng/dl in the non-fatty liver and was 44.4+/-1.5 ng/dl in fatty
      liver participants (p=0.02). 59% of patients with metabolic syndrome had fatty
      liver in ultrasonography. Conclusion: According to this study, there was a
      correlation between visfatin levels and fatty liver disease.

PMID- 29445658
TI  - Current status of health index in Tehran: A multidimensional approach.
AB  - Background: Health is an essential component of human rights and the rights are
      interdependent, indivisible, and correlated. The present study aimed at codifying
      a multidimensional health index according to multistage index development and
      describing the status of this index in 22 municipal districts of Tehran. Methods:
      This study was conducted using the data collected in the second round of Urban
      HEART Project of Tehran (2012-2013). The sample size was 34 700. To develop a
      multidimensional health index (MDHI), the nine steps of the Organization for
      Economic Cooperation and Development (OECD) were followed, from codifying
      theoretical framework to introducing the index. Results: According to the
      constructed MDHI, the districts no. 13, 10, 17, 1, 3, 4, and 22 had the best
      status and the district no. 8 the worst status. With respect to physical health,
      the districts no. 13, 17, 1, 3, 10, and 18 had the best status and the district
      no. 8 the worst. Concerning mental health, the districts no. 3, 6, 1, and 10 had
      the best status and the districts no. 8 and 12 the worst status. With respect to
      social health, the districts no. 10, 22, and 21 had the best status and the
      districts no. 6, 7, 12, and 14 the worst status. The analysis of sensitivity
      indicated that the MDHI was more sensitive towards physical health. Based on the
      mean, minimum, and maximum scores on each indicator of the questionnaires, the
      physical, mental, social, and MDHI status of Tehran residents (2012-2013) was
      high-medium, medium, low-medium, and high-medium, respectively. Conclusion: The
      right to health should be widely investigated, as it is a primary principle
      needed for sustainable development, which can be accomplished when the attitudes
      of different organizations towards the health construct are multidimensional
      rather than unidimensional.

PMID- 29445659
TI  - Clinical assessment of activities of daily living in acute stroke: Validation of
      the Persian version of Katz Index.
AB  - Background: Katz Index is a well-known index for assessing basic activities of
      daily living. The aim was to determine validity and reliability of the Katz Index
      in Iranian patients with acute stroke. Methods: Eighty-seven patients (56 male,
      31 female) with acute stroke (1-30 days post-stroke) participated in this
      psychometric properties study. Interval time for retest was 14 days. All
      participants were Iranian with Persian as native language, had no other major
      diseases (e.g. cancer, Alzheimer) and no psychiatric disorder. Cognitive mental
      score of all participants was above 18 (according to Mini-Mental State
      Examination). If they had another stroke during the following-up period, they
      were excluded from the study. Intraclass Correlation Coefficient (ICC), Standard
      Error of Measurement (SEM) and Minimum Detectable Change (MDC) were calculated to
      investigate the reliability of the KI. Criterion validity of the KI was assessed
      by Spearman's Correlation Coefficient (rho). Moreover, Confirmatory Factor
      Analysis (CFA) and Exploratory Factor Analysis (EFA) were performed to
      investigate the construct validity of the KI. Results: Inter-rater and intra
      rater reliability of Persian Katz Index were reasonable (ICC2,1=0.93,
      ICC2,1=0.83; respectively). Internal consistency of this index was high
      (cronbach's alpha=0.79). The high to excellent correlation was found between Katz
      Index and the motion (rho=0.88), self-care (rho=0.98), and total scores
      (rho=0.92) of Barthel Index. Factor analysis of the Persian Katz Index indicated
      two factors including motion (bathing, toileting, and transferring) and self-care
      (dressing, bowel & bladder control, and feeding). Conclusion: The results of this
      study suggest that Persian version of Katz Index in patients with acute stroke
      can be considered as an acceptable clinical instrument in practice and research.

PMID- 29445660
TI  - Health technology assessment of magnet therapy for relieving pain.
AB  - Background: Magnet therapy has been used increasingly as a new method to
      alleviate pain. Magnetic products are marketed with claims of effectiveness for
      reducing pain of various origins. However, there are inconsistent results from a
      limited number of randomized controlled trials (RCTs) testing the analgesic
      efficacy of magnet therapy. This study aimed to evaluate the safety and
      effectiveness of magnet therapy on reliving various types of pain. Methods: A
      systematic search of two main medical databases (Cochrane Library and Ovid
      Medline) was conducted from 1946 to May 2014. Only English systematic reviews
      that compared magnet therapy with other conventional treatments in patients with
      local pain in terms of pain relieving measures were included. The results of the
      included studies were thematically synthesized. Results: Eight studies were
      included. Magnet therapy could be used to alleviate pain of various origins
      including pain in various organs, arthritis, myofascial muscle pain, lower limb
      muscle cramps, carpal tunnel syndrome and pelvic pain. Results showed that the
      effectiveness of magnetic therapy was only approved in muscle pains, but its
      effectiveness in other indications and its application as a complementary
      treatment have not been established. Conclusion: According to the results, it
      seems that magnet therapy could not be an effective treatment for relieving
      different types of pain. Our results highlighted the need for further
      investigations to be done in order to support any recommendations about this
      technology.

PMID- 29445661
TI  - Does the normal four steps weight-bearing rule predict the need for radiography
      in cases of blunt ankle trauma?
AB  - Background: Ankle injuries are one of the most common complaints of patients
      presenting to emergency departments (ED). The Ottawa ankle rules (OAR) was
      introduced to help physicians to decide who may require x-ray for blunt injuries.
      The present study aimed at validating the four steps weight-bearing rule of OAR
      as a sole criterion. Methods: This prospective observational study was conducted
      on 214 patients with acute ankle injury who referred to 3 emergency departments
      over a 7-months period in 2008. Main outcome measures of this survey included the
      sensitivity, specificity, positive and negative predictive values, and the
      likelihood ratios (positive and negative) of the four steps weight-bearing rule.
      Results: In this study, 34 fractures were found among the patients. The decision
      rule had a sensitivity of 0.88 and specificity of 0.61 in detecting all midfoot
      and ankle fractures. Application of this rule by emergency medicine residents
      resulted in a 47% reduction in the use of midfoot and ankle radiography.
      Conclusion: Applying a four steps weight-bearing rule as a sole criterion to
      detect ankle fractures is not as accurate and sensitive as OAR. Solitary
      application of this rule may lead to an increasing number of missed fractures
      compared with OAR.

PMID- 29445662
TI  - Footprint as an alternative to X-ray in hallux valgus angle measurement.
AB  - Background: X- ray images provide accurate and reliable data in different foot
      pathologies. However, the accompanied complications will limit its use for
      epidemiological studies and research purposes, especially in children. Therefore,
      simple, accessible, and cost- effective methods such as footprint, with a good
      correlation with x-ray images, are needed to help diagnose different foot
      pathologies. In the present study, the accuracy of footprint technique in
      assessing hallux valgus angle (HVA) was evaluated based on x-ray images through
      measuring the angle between the medial border protrusion of the foot and the
      hallux. Methods: In this cross-sectional study, 42 participants with symptomatic
      hallux valgus were recruited. HVA was measured by both x-ray imaging and
      footprint. The differences between the two approaches were identified by applying
      correlation-coefficient test and reliability, which was assessed using interclass
      correlation (ICC). Results: A significant correlation was found between the HVA
      measured by x-ray and HVA by footprints (p< 0.001), and the ICC was upper than
      90%. Conclusion: Foot print is a reliable method for measuring HVA, as it was
      highly correlated with the HVAs obtained by x-ray imaging.

PMID- 29445663
TI  - Comparing minimally supervised home-based and closely supervised gym-based
      exercise programs in weight reduction and insulin resistance after bariatric
      surgery: A randomized clinical trial.
AB  - Background: Effectiveness of various exercise protocols in weight reduction after
      bariatric surgery has not been sufficiently explored in the literature. Thus, in
      the present study, we aimed at comparing the effect of minimally supervised home
      based and closely supervised gym-based exercise programs on weight reduction and
      insulin resistance after bariatric surgery. Methods: Females undergoing gastric
      bypass surgery were invited to participate in an exercise program and were
      randomly allocated into 2 groups using a random number generator in Excel. They
      were either offered a minimally supervised home-based (MSHB) or closely
      supervised gym-based (CSGB) exercise program. The CSGB protocol constitutes 2
      weekly training sessions under ACSM guidelines. In the MSHB protocol, the
      participants received a notebook containing a list of recommended aerobic and
      resistance exercises, a log to record their activity, and a schedule of follow-up
      phone calls and clinic visits. Both groups received a pedometer. We measured
      their weight, BMI, lipid profile, FBS, and insulin level at baseline and at 20
      weeks after the exercises, the results of which were compared using t test or
      Mann-Whitney U test at the end of the study. All the processes were observed by 1
      senior resident in sport medicine. Results: A total of 80 patients were recruited
      who were all able to complete our study (MSHB= 38 and CSGB= 42). The baseline
      comparison revealed that the 2 groups were similar. The mean change (reduction)
      in BMI was slightly better in CSGB (8.61 95% CI 7.76-9.45) compared with the MSHB
      (5.18 95% CI 3.91-6.46); p< 0.01. However, the 2 groups did not have a
      statistically significant difference in the amount of change in the other factors
      including FBS and Homa.ir. Conclusion: As we expected a non-inferiority result,
      our results showed that both MSHB and CSGB exercise methods are somewhat equally
      effective in improving lipid profile and insulin resistance in the 2 groups, but
      a slightly better effect on BMI was observed in CSGB group. With considerably
      lower costs of minimally supervised home- based exercise programs, both methods
      should be considered when there is lack of adequate funding.

PMID- 29445664
TI  - Unmet needs in Iranian cancer patients.
AB  - Background: The identification and management of unmet needs is an essential
      component of health care for the growing cancer patient population. Information
      about the prevalence of unmet need can help medical service planning/redesigning.
      Therefore, this study aimed to identify unmet needs in Iranian patients suffering
      from cancer. Methods: This cross-sectional correlational study was conducted on
      650 cancer patients admitted to the major medical centers in Mashhad and
      Neyshabur by census sampling. The data was gathered by the Survivor Unmet Needs
      Survey (SUNS). Data were analyzed using ANOVA, t-test and Pearson correlation.
      Results: Most of participants were female (56%, n=263) and Mashhad resident
      (67.1%, n=436). The most common cancers were colorectal (17.8 %, n=116), stomach
      (13.6%, n=88) and lung (9.4%, n=62), respectively. The highest unmet needs score
      belonged to work and financial needs (2.46 +/- 0.91), and the least was the
      emotional domain (1.92+/-0.90). Among demographic factors, a significant
      relationship was found between resident places (p<0.001), and cancer type
      (p<0.0001). Conclusion: This is the first study addressing the unmet needs of
      cancer patients in Iran. It reveals that cancer patients had a relative high
      number of unmet needs; this shows the necessity of including these factors in the
      routine assessment of all cancer patients and planning treatment interventions
      based on their individual's need.

PMID- 29445665
TI  - Envelope-based inter-aural time difference localization training to improve
      speech-in-noise perception in the elderly.
AB  - Background: Many elderly individuals complain of difficulty in understanding
      speech in noise despite having normal hearing thresholds. According to previous
      studies, auditory training leads to improvement in speech-in-noise perception,
      but these studies did not consider the etiology, so their results cannot be
      generalized. The present study aimed at investigating the effectiveness of
      envelopebased interaural time difference (ITD ENV) localization training on
      improving ITD threshold and speech-in-noise perception. Methods: Thirty-two
      elderly males aged 55 to 65 years with clinically diagnosed normal hearing at 250
      2000 Hertz, who suffered from speech-in-noise perception difficulty participated
      in this study. These individuals were randomly divided into training and control
      groups: 16 elderlies in the experimental group received envelope-based interaural
      time difference localization training in 9 sessions, but 16 matched elderlies in
      the control group did not receive any training. The ITD ENV threshold and spatial
      word recognition score (WRS) in noise were analyzed before and after the
      localization training. Results: Findings demonstrated that following the training
      program, the interaural time difference envelope threshold and spatial word
      recognition score (WRS) in noise were improved significantly in the experimental
      group (p<= 0.001). Moreover, a significant difference was detected in interaural
      time difference envelope threshold and spatial word recognition score (WRS) in
      noise (p<= 0.001) before and after the training in the experimental group.
      Conclusion: The results of the present study revealed the effectiveness of
      envelope- based interaural time difference localization training in localization
      ability and speech in noise perception in the elderlies with normal hearing up to
      2000 Hz who suffered from speech-in-noise perception difficulty.

PMID- 29445666
TI  - Perioperative changes in platelet count and function in patients undergoing
      cardiac surgery.
AB  - Background: Patients undergoing cardiac surgery are at increased risk of bleeding
      due to multifactorial coagulopathies. In the present study, we aimed at
      investigating the changes in platelet count and function during and after surgery
      as well as determining the association of the platelet dysfunction with bleeding
      and transfusion requirements in these patients. Methods: A total of 40 adult
      patients scheduled for elective valve coronary cardiac surgery were included in
      this prospective observational study. Changes in platelet count and function with
      ADP, acid arachidonic, and collagen (light transmission aggregometry) were
      analyzed at three time points: before CPB, after CPB, and 24 hours after end of
      surgery. Postoperative bleeding and intraoperative transfusion requirements were
      recorded. Results: There were a significant reverse correlation between CPB time
      and ADP-induced aggregation, particularly after CPB and postoperative AA-induced
      aggregation. There was not any significant correlation between platelet count and
      function at all-time points. Both platelet count and platelet aggregation
      significantly reduced during CPB. While platelet aggregation increased on
      postoperative Day 1, platelet count reduced by about 40% after CPB, and remained
      at this level postoperatively. Patients with abnormal ADP-induced aggregation had
      significant increased postoperative bleeding and transfusion requirements.
      Conclusion: The results of this study demonstrate that platelet count and
      platelet aggregation are reduced during CPB. Our results emphasized the effect of
      platelet dysfunction on increased postoperative bleeding and transfusion
      requirements. Perioperative monitoring of platelet function can be considered as
      a bleeding management strategy for implantation of PBM programs.

PMID- 29445667
TI  - Determination of lymphocytes surface markers in patients with thermal burns and
      the influence of burn size on mononuclear cell subsets.
AB  - Background: Thermal burn injuries impair the host defence system. Hence, in the
      present study, we aimed at investigating the changes in the number and phenotype
      of peripheral blood lymphocyte populations (T, B, and natural killer cells) and
      their subpopulations in patients with thermal burns and determining the
      relationships with different sizes of total body surface area (TBSA). Methods:
      Blood samples from 67 patients, admitted to Motahary Burn Center in Tehran, with
      burns from 30% to more than 70% TBSA were collected on Days 3 and 7 postburn.
      Lymphocytes and their subpopulations were identified by monoclonal antibodies.
      The cells were analyzed using flow cytometry. The results were compared with
      healthy controls. Results: In this study, 3 and 7 days after burn injury, the
      percentages of CD3+, CD4+ and CD8+ lymphocyte significantly decreased, CD4+/CD8+
      ratios were below the normal range, and CD19+ (B cells) significantly increased.
      No significant difference was obtained in the mean percentage of CD16+ (NK cells)
      between Days 3 and 7 postburn. Patients with burns of 30% TBSA or greater (>70%)
      had a significant reduction in CD3+, CD4+ and CD8+ ( T cells) numbers up to 7
      days compared with 3 days after burn injury. Patients with 30% to >70 % TBSA burn
      failed to show any significant changes in CD4+/CD8+ ratio as well as CD16+ (NK
      cells) 3 to 7 days after burn. In patients with burns more than 30% to>70% TBSA,
      CD19+ (B cells) number changes were found to be complicated after 3 and 7 days.
      Conclusion: The results of this study suggest that alterations of immune cell
      surface markers and TBSA% can reflect postburn lymphocyte activation.

PMID- 29445668
TI  - Cost-effectiveness of teriparatide compared with alendronate and risedronate for
      the treatment of postmenopausal osteoporosis patients in Iran.
AB  - Background: Hip, vertebral and wrist fractures are the most common consequences
      of osteoporosis. This study aimed at analyzing the cost-effectiveness of
      teriparatide (CinnoPar(r)), compared with alendronate and risedronate, in the
      treatment of women aged 60 and over with postmenopausal osteoporosis in Iran.
      Methods: A decision tree model with a 2-year time horizon was used to compare
      treatment with teriparatide (CinnoPar(r)) with the following treatment
      strategies: two years of treatment with alendronate and two years of treatment
      with risedronate in women aged 60 years and over or those at risk of
      osteoporosis. Cost per QALY was calculated for 3 treatment strategies from the
      model. After base case analysis, one-way sensitivity analysis was performed on
      key parameters of the model to assess their impact on the study results and the
      cost-effectiveness of different treatment strategies and the model robustness.
      TreeAge Pro 2006 software was used for modeling and data analysis. Results:
      Incremental cost-effectiveness ratio (ICER) of alendronate and teriparatide than
      risedronate (base treatment) were US$- 2178.03 and US$483,783.67 per QALY,
      respectively. Therefore, the dominant and cost-effective treatment option was
      alendronate. In the one-way sensitivity analysis, the impact of annual 25%
      increase or decrease in the teriparatide cost on its ICER was remarkable. Also,
      reducing the discount rate from 0.03 to 0.0 had the greatest impact on the ICER
      of the teriparatide. Conclusion: The treatment strategy of teriparatide is more
      expensive than risedronate and alendronate and is associated with very little
      increase in QALYs. A significant reduction in teriparatide price and a limit in
      its use only for high-risk women and for acute and short-term treatment courses
      can contribute to its cost-effectiveness.

PMID- 29445669
TI  - Males' perspectives on health in Iran: A grounded theory study.
AB  - Background: Males' health plays a basic role in the community's health,
      especially in family's health. Health is a multifaceted issue that affects people
      in all aspects. Health is also one of the 4 metaparadigm concepts in nursing.
      This study was conducted to explore males' perspectives on health. Methods: In
      this qualitative study conducted based on a grounded theory approach, 22 males
      were selected through a purposive sampling. Data were collected through semi
      structured interviews and continued until data saturation. Data analysis was done
      using Strauss and Corbin's three-stage coding process. Results: Based on the
      perspectives of the participants, 8 categories emerged, which are as follow:
      psychological health; physical health; family health; spiritual health; welfare
      and social health; health and relationships; sexual health; and occupational
      economic health. Psychological health was emerged as the core variable.
      Conclusion: As a multifaceted phenomenon, health is an individual's general
      condition in all these aspects, particularly psychological aspect. Males' health
      should be taken into account for the role they play in managing the family. Males
      as the family heads require evidence-based decision making and planning.

PMID- 29445670
TI  - General practitioners' views on key factors affecting their desired income: A
      principal component analysis approach.
AB  - Background: Based on the target income hypothesis, the economic behavior of
      physicians is mainly affected by their target income. This study aimed at
      designing an instrument to explain how general practitioners (GPs) set their
      desired income. Methods: A self-administered questionnaire of affecting factors
      on GPs' target income was extracted from literature reviews and a small
      qualitative study. Respondents were 666 GPs who completed the questionnaire
      (response rate= 52%) during 2 seasonal congresses of Iranian GPs. The principal
      component analysis (PCA) with varimax rotation was used to classify the variables
      and data reduction. Sample adequacy test, sphericity test, eigenvalues of
      components, and scree plot were evaluated for PCA. Cronbach's alpha was also
      checked to assess the internal consistency of the principal components. Results:
      The results of the KMO measure of sampling adequacy (0.657) and Bartlett's test
      of sphericity (809.05, p<0.001) revealed that the collected data were suitable
      for PCA. Based on the scree plot pattern and eigenvalues greater than 1, 6
      components including perceived comparative income, importance of responsiveness
      to patients, perceived socioeconomic status, economic expectations, socioeconomic
      status of paternal family, and provision of luxury services were selected, which
      explained 65.19% of the total variance. Finally, only those with a Cronbach's
      alpha value higher than 0.6 were considered reliable (the first 4 components).
      Conclusion: Based on the target income hypothesis, a physician's desired level of
      income affects their behavior. Our developed instrument and its mentioned
      components can be used in future studies related to GPs' behavior, especially
      those studies related to the economic aspects of GPs' behavior. It also helps
      formulate a better payment mechanism for primary care providers.

PMID- 29445671
TI  - A seroprevalence and relationship survey of brucellosis between pregnant women
      and women with spontaneous abortion in Iran.
AB  - Background: Brucellosis is one of the most prevalent diseases common between
      humans and animals. It is also called Malta fever, Undulant fever and
      Mediterranean fever. This disease is spread by consuming milk and its
      unpasteurized derivatives. Clinical symptoms of brucellosis in humans are fever,
      chills, headache, muscular pain, tiredness, loss of appetite, joint pain, weight
      loss, constipation, sore throat, and dry cough. The present study aimed at
      surveying the seroprevalence of brucellosis in pregnant women and those women who
      suffered from spontaneous abortion. Methods: This case- control study was
      conducted in Sanandaj (Iran) in 2016 and included 2 groups of pregnant women: one
      group included 160 pregnant women and the other included 160 women who suffered
      from spontaneous abortion. Then, the participants were asked to fill out the
      questionnaire. After receiving permission from an obstetrician, a 10-cc blood
      sample was taken from each person to be used in the Rose Bengal, Wright, 2ME, and
      Coombs tests. Independent samples t test and Chi-square test were used to analyze
      the data and compare the groups. Results: Mean+/-SD age of women in the case
      group was 30.9+/-7.3 years, while it was 27.74+/-5.41 years in control women. The
      Rose Bengal, Wright, and 2ME prevalence for both groups was negative, but the
      Coombs and Wright tests score was 33 (20.6%) in pregnant women and it was 27
      (16.9%) in women who experienced spontaneous abortion. No meaningful relationship
      was observed between spontaneous abortion and brucellosis (p= 0.39). Conclusion:
      Even though the present study did not find a meaningful relationship between
      spontaneous abortion and brucellosis (p=0.39), high brucella seroprevalence rates
      between both groups of women indicated that screening tests should be considered
      before gestation as an appropriate therapeutic strategy.

PMID- 29445672
TI  - Catastrophic health expenditure among households with members with special
      diseases: A case study in Kurdistan.
AB  - Background: One of the main goals of health systems is to protect people against
      financial risks associated with diseases that can be catastrophic for patients.
      In 2014, Health Sector Evolution Plan (HSEP) was implemented in Iran; one of the
      objectives of HSEP was to reduce out-of-pocket payments and provide more
      financial protection for people. Therefore, the present study aimed at exploring
      the likelihood of facing catastrophic health expenditures (CHE) among households
      with members suffering from dialysis, kidney transplant, or multiple sclerosis
      (MS) after the implementation of HSEP. Methods: A total number of 385 households
      were selected using stratified random sampling and were asked to complete the
      World Health Survey questionnaire through telephone conversations. As outlined by
      the World Health Organization (WHO), when household out-of-pocket expense for
      health services is >=40% of its capacity to pay, then that household is
      considered to be facing CHE. Furthermore, determinants of CHE were identified
      using logistic regression. Results: The percentage of facing catastrophic health
      care expenditures for households with a MS, dialysis, and kidney transplant
      patient was 20.6%, 18.7%, and 13.8%, respectively. Results of logistic regression
      analysis revealed that patient's economic status, level of education,
      supplementary insurance status, type of disease, multiple members with special
      diseases in the household, rural residence, use of inpatient, dental, and
      rehabilitation services were effective factors for determining the likelihood of
      facing CHE. Conclusion: Despite the implementation of HSEP, the percentage of CHE
      is still high for households that have members who suffer from special diseases.
      However, basic health insurance packages should be amended and more cost-sharing
      exemptions should be granted to provide more financial protection for the
      vulnerable households.

PMID- 29445673
TI  - Periodontitis in rheumatoid arthritis patients, abundance and association with
      disease activity.
AB  - Background: There are some discrepancy in association between activity of
      rheumatoid arthritis (RA) and periodontitis. The aim of this study was to
      evaluate the periodontal status of outpatients with RA. Methods: The study was
      conducted in 2013-14 in a rheumatology clinic in Sari, north of Iran on 74
      patients with RA. Evaluation of RA disease activity was according to disease
      activity score 28 (DAS28). Periodontitis was evaluated by probing depth (PD),
      gingival index (GI), clinical attachment level (CAL index), plaque index (PI),
      and panoramic X-ray. Statistical analysis included independent ttest and Mann
      Whitney U test for quantitative, and chi square and OR for qualitative variables
      and evaluation of RA activity and periodontitis severity. Results: The mean+/-SD
      of age and disease duration were 47.01+/-8.1 and 8.93+/-8.6 years, respectively
      and the mean+/-SD number of teeth was 20.70+/-6.8. Twenty-seven (36.5%) patients
      had moderate to severe disease. Forty-seven cases (63.5%) were found with
      periodontitis and 14 (12.2%) were identified to have moderate to severe
      periodontitis, unrelated to disease activity (p=0.22). For active/inactive
      periodontitis OR =1.33 (95% CI: 0.46 - 3.87) was computed. There was no
      association between RA disease activity and number of teeth, CAL, PI, PD, and GI,
      (p>0.05). Conclusion: About 60% of RA patients suffered from periodontitis, but
      there was not any significant relation between RA disease activity and severity
      of periodontitis. Periodontitis may interfere with management and follow up of
      RA, so periodic periodontal examination is suggested in these patients.

PMID- 29445674
TI  - Experiences of substance abusers from methadone maintenance therapy.
AB  - Background: Substance abusers are not able to withdraw drugs eternally despite
      the abundance of different treatments; therefore, withdrawal programs are not
      quite successful and notwithstanding all the successes of methadone maintenance
      therapy, there are some defects found in the manner this treatment is applied.
      Thus, this study was conducted to explore the experience of drug abusers
      regarding methadone maintenance therapy. Methods: This is a qualitative study
      using content analysis methodology. The research community includes drug abusers
      admitted to the treatment centers of the western cities of Mazandaran Province,
      Iran in 2016. The sampling was purposive and the data were collected by face-to
      face single interviews with 20 patients. The interviews were continued up to data
      saturation. Finally, the Lundman and Grenheim method was used to analyze the
      interviews and the four criteria of Guba and Lincoln were applied to check data
      integrity. Results: "Buying time," "methadone dependence," and "looking from a
      narrow view to the patient" were the main three categories that fit the results.
      Conclusion: Governmental free services for drug abusers; paying attention to
      different aspects of treatment such as mental, emotional, and social recovery;
      lifelong support of the family and society members; and balance in prescribing
      and following the treatment process prescribed by health care providers can
      enhance both the quality and safety of the treatment process. Psychological
      consultation alongside social services can facilitate the recovery process in
      methadone maintenance therapy.

PMID- 29445675
TI  - Psychosocial experiences of the internet in a group of adolescents: A qualitative
      content analysis.
AB  - Background: Social networking has a dramatically increasing trend among
      adolescents. By creating novel models of content production, distribution, and
      reception, this space has introduced opportunities and threats for adolescents,
      which must be understood in relation with their health status. This study was
      conducted with the aim of describing the psychosocial experiences of Iranian
      adolescents in the Internet's virtual space. Methods: The present qualitative
      formal content analysis was conducted in Mashhad a city Iran. The participants
      included 32 adolescents of 13-18 years of age. Data were collected through 32
      semi-structured individual and group interviews with maximum variation. The data
      were recorded, transcribed, and then analyzed via MAXQ 10 software. Results: In
      this study, 2 main themes of "moving towards constructiveness" and "perceiving
      social and psychological tensions" were formed. Accordingly, 9 subcategories were
      formulated including: increasing the social capital, a good feeling in life,
      escaping loneliness, being seen in the social network, intelligent selection of
      content, perceived threats, temptation, decline of behavioral values and
      principles, and emotional and social helplessness. Conclusion: Adolescents'
      positive and negative experiences in the Internet form based on personal and
      environmental factors. These experiences affect the mental and social dimensions
      of their health. These factors call for the attention of scholars and
      policymakers for developing enabling strategies for adolescents, and their
      families and for experts for promoting adolescents' health.

PMID- 29445676
TI  - Rationing in health systems: A critical review.
AB  - Background: It is difficult to provide health care services to all those in need
      of such services due to limited resources and unlimited demands. Thus, priority
      setting and rationing have to be applied. This study aimed at critically
      examining the concept of rationing in health sector and identifying its purposes,
      influencing factors, mechanisms, and outcomes. Methods: The critical interpretive
      synthesis methodology was used in this study. PubMed, Cochrane, and Proquest
      databases were searched using the related key words to find related documents
      published between 1970 and 2015. In total, 161 published reports were reviewed
      and included in the study. Thematic content analysis was applied for data
      analysis. Results: Health services rationing means restricting the access of some
      people to useful or potentially useful health services due to budgetary
      limitation. The inherent features of the health market and health services,
      limited resources, and unlimited needs necessitate health services rationing.
      Rationing can be applied in 4 levels: health care policy- makers, health care
      managers, health care providers, and patients. Health care rationing can be
      accomplished through fixed budget, benefit package, payment mechanisms, queuing,
      copayments, and deductibles. Conclusion: This paper enriched our understanding of
      health services rationing and its mechanisms at various levels and contributed to
      the literature by broadly conceptualizing health services rationing.

PMID- 29445677
TI  - Accuracy of ultrasonography in diagnosing acute appendicitis during pregnancy
      based on surgical findings.
AB  - Background: Acute appendicitis is the most common nonobstetric surgical problem
      in pregnancy. Common signs and symptoms of appendicitis are less reliable during
      pregnancy due to physiological changes; thus, the role of imaging becomes
      prominent. Thus, in the present study, we aimed at assessing the accuracy of
      sonography in diagnosing acute appendicitis during pregnancy. Methods: In this
      prospective analytic study, among 1000 patients diagnosed and treated as acute
      appendicitis, clinical and sonographic findings of 58 consecutive pregnant
      patients, who underwent appendectomy, were recorded and analyzed. All surgically
      resected samples were evaluated and confirmed through histological evaluation.
      Sonographic criteria were utilized to judge the results for appendicitis.
      Diagnostic test performance characteristics (sensitivity, specificity, predictive
      values, and likelihood ratios) were calculated. Results: The mean age of the
      patients was 27.1+/-4.9 years, and the most common clinical symptom was right
      lower quadrant pain. There was no significant difference in the mean leukocyte
      count between the appendicitis group and normal appendix group (p=0.768). Left
      shift was also unrelated with the appendix pathology (p= 0.549). The sensitivity,
      specificity, predictive values (positive and negative), and likelihood ratios
      (positive and negative) were 80%, 75%, 91.4%, 52.9%, 3.2, and 0.26, respectively
      during all trimesters of pregnancy. Conclusion: Ultrasonography is the initially
      preferred imaging modality in pregnant women suspected of having acute
      appendicitis with an acceptable sensitivity; however, application of other
      imaging modalities such as CT scan or MRI is recommended after inconclusive
      ultrasonography results.

PMID- 29445678
TI  - Effectiveness of psychosocial interventions in abused children and their
      families.
AB  - Background: Child abuse is a significant public health and social problem
      worldwide. It can be described as a failure to provide care and protection for
      children by the parents or other caregivers. This study aimed at evaluating the
      effectiveness of psychosocial interventions in abused children and their
      families. Methods: This quasi-experimental study was conducted in the
      psychosocial support unit of a pediatric hospital in Bandar Abbas, Iran, from
      2012 to 2013. The participants consisted of child abuse cases and their parents
      who referred to the psychosocial support unit to receive services. Services
      delivered in this unit included parenting skills training, psychiatric
      treatments, and supportive services. The effectiveness of the interventions was
      assessed with Child Abuse Questionnaire, General Health Questionnaire (GHQ), and
      Strengths and Difficulties Questionnaires (SDQ). Participants were assessed at
      baseline, at 3, and 6 months follow-ups. ANOVA with repeated measures and
      Friedman test were used to evaluate the effect of the interventions. Results: A
      total of 68 children and their parents enrolled in this study, of whom 53% were
      males. Post-intervention follow-ups revealed significant changes in mothers'
      general health questionnaire (p<0.001), and children's conduct problem (p<0.05),
      hyperactivity (p<0.001), and peer problems (p<0.05). Physical and emotional
      abuses significantly decreased (p<0.001). Conclusion: Our findings revealed that
      psychosocial interventions effectively improved child-parents interaction and
      mental health of parents. The effectiveness of interventions based on subgroup
      analysis and implications of the results have been discussed for further
      development of psychosocial interventions in the health system.

PMID- 29445679
TI  - Sentinel lymph node in cervical cancer.
AB  - Background: Cervical cancer is the second most common type of cancer among women.
      Effective screening programs can help cancer detection in early phases and reduce
      death. Metastasis to lymph nodes is one of the most prognostic factors in
      patients who underwent surgery. Also, a positive result from pathology report
      alert oncologist as a cause of death. Sentinel lymph node biopsy has been widely
      studied and clinically used for many types of cancer. Methods: Two techniques
      exist for detecting sentinel node in cervical cancer, which are Blue dye and
      gamma probe with radioactive isotope (99mTc). Moreover, lymphoscintigraphy has
      many advantages over the stain method. Detecting the sentinel node is performed
      via laparoscopy or laparotomy; former method is better and more accurate.
      Results: Various researchers have focused on this method and its positive
      results; its superiority against full lymphadenectomy has been declared in
      previous studies. Moreover, the role of sentinel lymph nodes biopsy in cervical
      cancer is still being extensively studied. Sentinel lymph nodes (SLN) method has
      a higher accuracy level to detect metastasis. Conclusion: Hence, it can be
      considered as a more appropriate alternative for pelvic lymph node dissection
      (PLND), which is a standard technique. Altering the method to a standard clinical
      method needs in-depth researches and studies.

PMID- 29445680
TI  - Cultural barriers in access to healthcare services for people with disability in
      Iran: A qualitative study.
AB  - Background: People with disability experience various problems to access to
      healthcare services. This study aimed to identify cultural barriers in access to
      healthcare services for people with disability in Iran. Methods: We conducted a
      qualitative study using content analysis to identify the cultural barriers. We
      used semi-structured interviews to collect data. Participants were selected
      through purposeful sampling with maximum variation. 50 individual interviews were
      conducted with three groups of people with disability, healthcare services
      providers and policy makers, September to May 2015, at different locations in
      Tehran, Iran. Results: We identified a number of different cultural barriers in
      access to health services for people with disability in Iran. These related to
      health service providers, namely reluctance to provide health services and
      disrespect; related to People with disability, namely denial of disability,
      disproportionate expectation, shame and insufficient sociocultural supports; and
      related to policy makers, namely lack of concern, little attention to the culture
      of disability and discrimination. We categorized misconception as a barrier that
      was observed at all levels of the society. Conclusion: Disability is a reality
      that some human being may experience and live with it. The negative attitude
      towards people with disability has a close relationship with the cultural norms
      of a society. The culture of disability in different dimensions should be a
      priority for all policy makers. Removing cultural barriers in access to
      healthcare for people with a disability needs collective efforts and
      collaborations among all stakeholders.

PMID- 29445681
TI  - Digital games in medical education: Key terms, concepts, and definitions.
AB  - Introduction: Game-based education is fast becoming a key instrument in medical
      education. Method: In this study, papers related to games were filtered and
      limited to full-text peer-reviewed published in English. Results: To the best of
      researchers' knowledge, the concepts used in the literature are varied and
      distinct, and the literature is not conclusive on the definition of educational
      games for medical education. Conclusion: This paper attempts to classify terms,
      concepts and definitions common to gamification in medical education.

PMID- 29445682
TI  - Changes of the brain's bioelectrical activity in cognition, consciousness, and
      some mental disorders.
AB  - Background: An electroencephalogram (EEG) is an accepted method in
      neurophysiology with a wide application. Different types of brain rhythms
      indicate that simultaneous activity of the brain cortex neurons depend on the
      person's mental state. Method: we have focus on reviewing the existing literature
      pertaining to changes of the brain's bioelectrical activity that recorded from
      the scalp in different conditions such as cognition and some mental disorders.
      Result: The frequency of brain waves may indicate sleep, consciousness,
      cognition, and some mental disorders. Slow brain waves are seen in some
      conditions such as sleep, coma, brain death, depression, autism, brain tumors,
      obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder
      (ADHD), and encephalitis, while rapid waves are generally reported in conditions
      such as epilepsy, anxiety, posttraumatic stress disorder (PTSD), and drug abuse.
      Conclusion: Increase in the EEG rhythm is a marker of high brain activity that
      leads to high degrees of consciousness, while slow waves are suggestive of less
      brain activity. The pattern of EEG rhythm can be an indicator of some mental
      disorders, too.

PMID- 29445683
TI  - Comparison of the Joel-Cohen-based technique and the transverse Pfannenstiel for
      caesarean section for safety and effectiveness: A systematic review and meta
      analysis.
AB  - Background: Caesarean section (C-section) is the most common surgery among women
      worldwide, and the global rate of this surgical procedure has been continuously
      rising. Hence, it is significantly crucial to develop and apply highly effective
      and safe caesarean section techniques. In this review study, we aimed at
      assessing the safety and effectiveness of the Joel-Cohen-based technique and
      comparing the results with the transverse Pfannenstiel incision for C-section.
      Methods: In this study, various reliable databases such as the PubMed Central,
      COCHRANE, DARE, and Ovid MEDLINE were targeted. Reviews, systematic reviews, and
      randomized clinical trial studies comparing the Joel-Cohen-based technique and
      the transverse Pfannenstiel incision were selected based on the inclusion
      criteria. Selected studies were checked by 2 independent reviewers based on the
      inclusion criteria, and the quality of these studies was assessed. Then, their
      data were extracted and analyzed. Results: Five randomized clinical trial studies
      met the inclusion criteria. According to the exiting evidence, statistical
      results of the Joel-Cohen-based technique showed that this technique is more
      effective compared to the transverse Pfannenstiel incision. Metaanalysis results
      of the 3 outcomes were as follow: operation time (5 trials, 764 women; WMD -9.78;
      95% CI:-14.49-5.07 minutes, p<0.001), blood loss (3 trials, 309 women; WMD 
      53.23ml; 95% -CI: 90.20-16.26 ml, p= 0.004), and post-operative hospital stay (3
      trials, 453 women; WMD -.69 day; 95% CI: 1.4-0.03 day, p<0.001). Statistical
      results revealed a significant difference between the 2 techniques. Conclusion:
      According to the literature, despite having a number of side effects, the Joel
      Cohen-based technique is generally more effective than the Pfannenstiel incision
      technique. In addition, it was recommended that the Joel-Cohen-based technique be
      used as a replacement for the Pfannenstiel incision technique according to the
      surgeons' preferences and the patients' conditions.

PMID- 29445684
TI  - Efficacy of commercial formulas in comparison with home-made formulas for enteral
      feeding: A critical review.
AB  - Background: In several disease conditions, patients must inevitably be nourished
      by enteral feeding (EF). Though in many countries, commercial formulas are
      routinely used for EF, in Iran still home-made formulas are commonly employed as
      commercial formulas are not covered by insurance. This may pose patients to
      malnutrition and bring about further costs. The aim of this study was to evaluate
      the efficacy of EF commercial formulas in comparison with home-made formulas and
      thus to make further evidence for insurance policy-making Methods: Medline,
      Cochrane, Embass and Center for Review & Dissemination (CRD) as well as IranDoc
      and SID databases were searched. Keywords included formula, ICU, and enteral
      nutrition or tube feeding. No clinical trial study on the efficacy of EF formulas
      was found. Therefore, the compositions of available formulas and their cost
      effectiveness were evaluated based on the clinical guidelines of scientific
      bodies such as American Society for Parenteral and Enteral Nutrition (ASPEN),
      European Society for Parenteral and Enteral Nutrition (ESPEN) and relative
      articles available in PubMed. In addition, the expert opinions were also taken
      into consideration. Results: Domestic commercial formulas seemed to less merit
      dietary recommended intakes, i.e. the amount of some nutrients were much higher,
      and some others were much lower than the recommended values. The amount of
      several micronutrients including vitamins B1, B6, C, D and K, as well as iron,
      calcium and magnesium were not sufficient to meet the body needs in most
      commercial formulas upon receiving 2000 kilocalories and less. Conclusion:
      Clinical studies on the efficacy of commercial formulas in comparison with home
      made formulas are needed. Meanwhile, making suitable conditions for increasing
      the diversity of artificial nutrition products in the market would help clinical
      nutritionists to make better choices according to their patients conditions and
      to reduce the costs, as well.

PMID- 29445685
TI  - Comparison of intramuscular progesterone with oral nifedipine for treating
      threatened preterm labor: A randomized controlled trial.
AB  - Background: Threatened preterm labor (TPL) is the leading cause of
      hospitalization during pregnancy. Tocolytic agents are the primary therapeutic
      options for TPL. The aim of this study is to compare intramuscular progesterone
      with oral nifedipine as a tocolytic agent. Methods: This randomized controlled
      trial was carried out in a teaching hospital (Shahid Akbarabadi) in Tehran, Iran,
      from December 2011 to November 2012. Three hundred and fifteen singleton pregnant
      women aged >18 yrs at 26-34 weeks' gestation with the diagnosis of threatened
      preterm labor (TPL) were randomly received either intramuscular progesterone or
      oral nifedipine for tocolysis. Maternal and neonatal outcomes were then compared
      between the two interventions. P value less than 0.05 was considered
      statistically significant. IRCT registration number of this study is
      IRCT201112198469N1 Results: The success rate of progesterone and nifedipine in
      treating TPL were 83% and 82.7%, respectively. There was no significant
      difference between the two interventions with regard to gestational age at
      delivery, type of delivery, the time interval until the delivery, birth weight,
      NICU admission rate and hospital stays. Progesterone administration was
      associated with lower duration of NICU stay as compared with nifedipine (0.33+/
      0.77 days vs.1.5+/-3.2 days, p<0.05). None of the two drugs caused any major side
      effects. Conclusion: Single dose intramuscular progesterone is as effective as
      oral nifedipine in treating TPL. It also significantly reduces the NICU stay.

PMID- 29445686
TI  - Prevalence of proline racemase/ hydroxyproline epimerase gene in human brucella
      isolates in Iran.
AB  - Background: Human brucellosis is a zoonotic disease caused by Brucella
      melitensis, Brucella abortus, and Brucella suis. Brucella causes a chronic
      disease, which subverts the immune defense system of their hosts. In this study,
      the prevalence of an important Brucella virulence determinant, prpA, which can
      modulate immune response, was determined in human isolates. Methods: Polymerase
      chain reaction (PCR) assay was standardized and applied to 37 isolates obtained
      from patient's specimens. Primers for prpA gene were designed and evaluated using
      bioinformatic tools. DNA sequencing was performed for further verification.
      Results: In the 37 Brucella isolates (31 Brucella melitensis and 6 Brucella
      abortus), 32 (86.4%) carried prpA gene. Conclusion: Presence of prpA gene in most
      isolates indicates the high prevalence of this gene among Iranian isolates and
      emphasizes its role in pathogenicity of this organism.

PMID- 29445687
TI  - Gender is a risk factor in patients with gastroesophageal reflux disease.
AB  - Background: Prevalence of gastroesophageal reflux disease (GERD) has increased in
      the last decades, and it is now one of the most common chronic and recurrent
      diseases. The present study aimed at determining the frequency of gender (sex)
      and age in Iranian patients with GERD symptoms. Methods: In this study, 803
      patients aged 11 to 84 years, with erosive and nonerosive gastroesophageal reflux
      diseases, based on the questionnaire and esophagogastroduodenoscopy findings,
      participated. The female group was compared with the male group with respect to
      age, symptoms, esophageal injury, and hiatus hernia. Results: Of the 803
      participants, 60.5% (n= 486) were female, and 69.2% (n= 555) were younger than 50
      years. Of those patients older than 50 years, 32.8% (n= 81) were female.
      Moreover, 31.0% (n= 249) of the patients had erosive esophagitis (ERD), and 69.0%
      (n= 254) had normal esophageal mucosa (NERD).The female to male ratio was 1/1.06
      and 1.94/1 in ERD and NERD patients, respectively. Hiatal hernia was more
      prevalent in females than in males. Conclusion: Nonerosive reflux disease, as a
      gastroesophageal reflux disease (GERD), was more common in females than in males.
      GERD became more prevalent with increase in age. Gender and hiatal hernias were 2
      potential risk factors of GERD.

PMID- 29445688
TI  - Complementary health insurance, out- of- pocket expenditures, and health services
      utilization: A population- based survey.
AB  - Background: Studies have shown that people using complementary health insurances
      have more access to health services than others. In the present study, we aimed
      at finding the differences between out- of- pocket payments and health service
      utilizations in complementary health insurances (CHIs) users and nonusers.
      Methods: Propensity score matching was used to compare the 2 groups. First,
      confounder variables were identified, and then propensity score matching was used
      to compare out- of- pocket expenditures with dental, general physician, hospital
      inpatient, emergency services, nursing, midwifery, laboratory services,
      specialists and rehabilitation services utilization. Results: Our results
      revealed no significant differences between the 2 groups in out- of- pocket
      health expenditures. Also, the specialist visits, inpatient services at the
      hospital, and dental services were higher in people who used CHIs compared to
      nonusers. Conclusion: People did not change their budget share for health care
      services after using CHIs. The payments were equal for people who were not CHIs
      users due to the increase in the quantity of the services.

PMID- 29445689
TI  - The effect of 3,4- methylenedioxymethamphetamine on expression of neurotrophic
      factors in hippocampus of male rats.
AB  - Background: 3,4- methylenedioxymethamphetamine (MDMA) is a chemical derivative of
      amphetamine that can induce learning and memory impairment. Due to the effect of
      neurotrophins on memory and learning, the impact of MDMA was evaluated on the
      brain - derived neurotrophic factor (BDNF), neurotrophin- 4 (NT-4), and
      tropomyosin- related kinase B (Trk- beta) expression in the hippocampus. Methods:
      In this study, 20 adult male Wistar rats (200-250 g) received saline (1 mL) or 10
      mg/kg of MDMA intraperitoneally as single or multiple injection for 2 consecutive
      days per week for 2 months. Expression of BDNF, Trk-beta, and NT4 were assessed
      using Western blotting and RT PCR methods. Results: Our results revealed that the
      expression of BDNF, Trk- beta, and NT4 proteins and genes significantly decreased
      in MDMA groups compared to the sham group (p<0.05). Furthermore, the acute group
      showed the lowest expression of these proteins. Conclusion: The results of the
      present study suggest that ecstasy administration may downregulate the expression
      of BDNF, Trk- beta, and NT-4 in hippocampus, which is more extensive in case of
      acute treatment. It seems that in the chronic group, hippocampus was able to
      compensate the ecstasy- induced neurotoxicity.

PMID- 29445690
TI  - The paced auditory serial addition test for working memory assessment:
      Psychometric properties.
AB  - Background: The paced auditory serial addition test (PASAT) was primarily
      developed to assess the effects of traumatic brain injury on cognitive
      functioning. Working memory (WM) is one of the most important aspects of
      cognitive function, and WM impairment is one of the clinically remarkable signs
      of aphasia. To develop the Persian version of PASAT, an initial version was used
      in individuals with aphasia (IWA). Methods: In this study, 25 individuals with
      aphasia (29-60 years) and 85 controls (18-60 years) were included. PASAT was
      presented in the form of recorded 61 single-digit numbers (1 to 9). The
      participants repeatedly added the 2 recent digits. The psychometric properties of
      PASAT including convergent validity (using the digit memory span tasks),
      divergent validity (using results in the control group and IWA group), and face
      validity were investigated. Test-retest reliability was considered as well.
      Results: The relationship between the PASAT and digit memory span tests was
      moderate to strong in the control group (forward digit memory span test: r= 0.52,
      p< 0.0001; backward digit memory span test: r = 0.48, p< 0.0001). A strong
      relationship was found in IWA (forward digit memory span test: r= 0.72, p<
      0.0001; backward digit memory span test: r= 0.53, p= 0.006). Also, strong
      testretest reliability (intraclass correlation= 0.95, p< 0.0001) was observed.
      Conclusion: According to our results, the PASAT is a valid and reliable test to
      assess working memory, particularly in IWA. It could be used as a feasible tool
      for clinical and research applications.

PMID- 29445692
TI  - Does smoking status affect cost of hospitalization? Evidence from three main
      diseases associated with smoking in Iran.
AB  - Background: Smoking is recognized as one of the main public health problems
      worldwide and is accounted for a high financial burden to healthcare systems and
      the society as a whole. This study was aimed at examining the effect of smoking
      status on cost of hospitalization among patients with lung cancer (LC), chronic
      obstructive pulmonary disease (COPD) and ischemic heart diseases (IHD) in Iran in
      2014. Methods: A total of 1,271 patients (consisting of 415 LC, 427 COPD and 429
      IHD patients) were included in the study. Data on age, sex, and insurance status,
      length of hospital stay and cost of hospitalization were extracted from the
      medical records of the patients. The smoking status of the patients was obtained
      through a telephone survey. A generalized linear model (GLM) was used to compare
      the costs of hospitalization of current, former and never smokers. The analysis
      was done using Stata v.12. Results: The mean+/-SD cost of hospitalization per
      patient was 45.6 +/- 41.8 million IR for current smokers, 34.8+/-23 million IR
      for former smokers and 27.6+/-24.6 million IR for never smokers, respectively.
      The findings indicated that the cost of hospitalization for current and former
      smokers was 65% and 26% in the unadjusted model and 35% and 24% in the adjusted
      model higher than for never smokers. Conclusion: The findings revealed that
      smoking drains a large hospital resource and imposes a high financial burden on
      the health system and the society. Therefore, efforts should focus on reducing
      the prevalence of smoking and the negative economic consequences of smoking.

PMID- 29445691
TI  - Study of Porphyromonas gingivalis in periodontal diseases: A systematic review
      and meta-analysis.
AB  - Background: The mouth cavity hosts various types of anaerobic bacteria including
      Porphyromonas gingivalis, which causes periodontal inflammatory diseases. P.
      gingivalis is a gram-negative oral anaerobe and is considered as a main
      etiological factor in periodontal diseases. Several studies have reported a
      relationship between P. gingivalis in individuals with periodontal diseases and a
      critical role of this bacterium in the pathogenesis of periodontal diseases. The
      present study aimed at estimating this probability using a meta-analysis.
      Methods: We searched several databases including PubMed, Scopus, Google Scholar,
      and Web of Science to identify case-control studies addressing the relationship
      between P. gingivalis with periodontal diseases. A total of 49 reports published
      from different countries from 1993 to 2014 were included in this study. I2
      (heterogeneity index) statistics were calculated to examine heterogeneity. Data
      were analyzed using STATA Version 11. Results: After a detailed analysis of the
      selected articles, 49 case-control studies with 5924 individuals fulfilled the
      inclusion criteria for the meta-analysis. The healthy controls included 2600
      healthy individuals with a Mean+/-SD age of 36.56+/-7.45 years. The periodontal
      diseases group included 3356 patients with a mean age of 43.62+/-8.35 years.
      There was a statistically significant difference between P. gingivalis in
      periodontal patients and healthy controls; 9.24 (95% CI: 5.78 to 14.77; P =
      0.000). In the other word, there was a significant relationship between the
      presence of P. gingivalis and periodontal diseases. Conclusion: Analyzing the
      results of the present study, we found a strong association between the presence
      of P. gingivalis and periodontal diseases. This result suggests that another
      research is needed to further assess this subject.

PMID- 29445693
TI  - Antibacterial activity of amino- and amido- terminated poly (amidoamine)-G6
      dendrimer on isolated bacteria from clinical specimens and standard strains.
AB  - Background: Nanoscale poly (amidoamine) dendrimers have been investigated for
      their biological demands, but their antibacterial activity has not been widely
      discovered. Thus, the sixth generation of poly (amidoamine) dendrimer (PAMAM-G6)
      was synthesized and its antibacterial activities were evaluated on Gram-negative
      bacteria; P. aeruginosa, E. coli, A. baumannii, S. typhimurium, S. dysenteriae,
      K. pneumoniae, P. mirabilis, and Gram-positive bacteria, and S.aureus and B.
      subtilis, which were isolated from different clinical specimens and standard
      strains of these bacteria. Methods: In this study, 980 specimens including urine
      (47%), blood (27%), sputum (13%), wounds (8%), and burns (5%) were collected from
      clinical specimens of 16 hospitals and clinics in city of Sabzevar, Iran. Then,
      the target bacteria were isolated and identified using standard methods. Minimum
      inhibitory concentration and minimum bactericidal concentrations against Gram
      positive and Gram-negative bacteria were determined according to guidelines
      described by clinical and laboratory standards institute (CLSI). Standard discs
      were prepared using 0.025, 0.25, 2.5, and 25 MUg/mL concentrations of PAMAM-G6 on
      Mueller-Hinton agar plates to determinate the zone of inhibition. The
      cytotoxicity of PAMAM-G6 dendrimer was evaluated in HCT116 cells by MTT assay.
      Results: The most important isolated bacteria were E. coli (23.65%), S. aureus
      (24.7%), P. aeruginosa (10.49%), B. subtilis (7.7%), S. typhimurium (8.87%), A.
      baumannii (7.02%), K. pneumoniae (7.1%), P. mirabilis (6.46%), and S. dysenteriae
      (3.6%). Moreover, it was found that poly (amidoamine)-G6 exhibited more
      antibacterial efficacy on standard strains than isolated bacteria from clinical
      samples (p<0.05). The cytotoxicity of PAMAM-G6 to the cells showed that
      cytotoxicity depended on the concentration level and exposure time. Conclusion:
      The PAMAM-G6 dendrimer showed a positive impact on the removal of dominant
      bacterial isolated from clinical specimens and standard strains.

PMID- 29445694
TI  - P-value: What is and what is not.
AB  - The misinterpretation and misuse of p-value have been increasing for decades. In
      March 2016, the American Statistical Association released a statement to warn
      about the use and interpretation of p-value. In this study, we provided a
      definition and discussion of pvalue and emphasized the importance of its accurate
      interpretation.

PMID- 29445695
TI  - Serum mannan-binding lectin in patients with pulmonary tuberculosis: Its lack of
      a relationship to the disease and response to treatment.
AB  - Background: Lectin pathway mediates complement activation, which is activated by
      many microorganisms. This study aimed at determining the serum levels of mannose
      binding lectin (MBL) in patients with pulmonary tuberculosis, assessing its
      relationship to antiuberculosis treatment response, and comparing them with a
      control group. Methods: This cross-sectional study was conducted on patients with
      pulmonary tuberculosis during 2012 and 2013 in South West of Iran. PPD-ST
      negative individuals were selected as controls from healthy relatives of
      patients. Serum MBL levels were measured using ELISA kit (Human MBL HK323,
      Hycultbiotech Company, Netherlands). All patients were followed- up for response
      to treatment. We applied Mann-Whitney and Fisher's exact tests and used SPSS
      Version 17 software for statistical analysis. Results: The study included 62
      patients as the case group and 63 noninfected TB patients as the control group.
      The MBL (ng/mL) in patients with pulmonary tuberculosis (median = 1012) was
      significantly (p= 0.037) higher than that of the control group (median= 296.2).
      No significant difference was found in the MBL level (ng/mL) between patients
      with response to antituberculosis treatment (median= 1012) and patients with
      treatment failure (median= 798.9) (p= 0.84). Conclusion: MBL may be involved in
      the pathogenesis of tuberculosis and in the low values that are protective
      against tuberculosis, and it seems that it has no effect on the antituberculosis
      treatment response.

PMID- 29445696
TI  - Identifying training and informational components to develop a psoriasis self-
      management application.
AB  - Background: Psoriasis is a complex disease with lifelong emotional and social
      consequences for affected patients. It also reduces the patients' quality of life
      and requires a long-term management. Therefore, in addition to appropriate
      treatment of the disease, selfmanagement strategies to improve patient health and
      quality of life are essential. On the other hand, smartphone-based applications
      alter the way people interact with health care and public health systems. This
      study aimed at identifying training and informational components to develop a
      psoriasis self- management application. Methods: This descriptive-analytic study
      was conducted on 100 patients with psoriasis and 26 dermatologists who were
      selected randomly, using Morgan table. The data were collected using a researcher
      made questionnaire, which included demographic and clinical information,
      lifestyle training and management, and application capabilities in psoriasis self
      management. A group of experts and a test-retest method were used to confirm the
      validity and reliability of the questionnaire, respectively. Results: The mean
      scores for demographic and clinical information, lifestyle training and
      management, and application capabilities in self-management were 80.55%, 85.7%,
      and 88.8% from the patients' perspective, and 83.7%, 71%, and 75% from the
      specialists' viewpoint, respectively. Conclusion: Determining self-management
      components by patients as persons who are suffering from the disease and
      physicians as specialists in the field will be helpful in efficient psoriasis
      self-management. It is more likely that self-reliant patients, who are aware of
      the benefits and risks of their disease management application, will follow their
      treatment plan and pursue the management of their disease more seriously.

PMID- 29445697
TI  - Social accounting matrix and the effects of economic reform on health price index
      and household expenditures: Evidence from Iran.
AB  - Background: Socioeconomic indicators are the main factors that affect health
      outcome. Health price index (HPI) and households living costs (HLC) are affected
      by economic reform. This study aimed at examining the effect of subsidy targeting
      plan (STP) on HPI and HLC. Methods: The social accounting matrix was used to
      study the direct and indirect effects of STP. We chose 11 health related goods
      and services including insurance, compulsory social security services, hospital
      services, medical and dental services, other human health services, veterinary
      services, social services, environmental health services, laundry& cleaning and
      dyeing services, cosmetic and physical health services, and pharmaceutical
      products in the social accounting matrix to examine the health price index. Data
      were analyzed by the I-O&SAM software. Results: Due to the subsidy release on
      energy, water, and bread prices, we found that (i) health related goods and
      services groups' price index rose between 33.43% and 77.3%, (ii) the living cost
      index of urban households increased between 48.75% and 58.21%, and (iii) the
      living cost index of rural households grew between 53.51% and 68.23%. The results
      demonstrated that the elimination of subsidy would have negative effects on
      health subdivision and households' costs such that subsidy elimination increased
      the health prices index and the household living costs, especially among low
      income families. The STP had considerable effects on health subdivision price
      index. Conclusion: The elimination or reduction of energy carriers and basic
      commodities subsidies have changed health price and households living cost index.
      Therefore, the policymakers should consider controlling the price of health
      sectors, price fluctuations and shocks.

PMID- 29445698
TI  - The impact of computerized physician order entry on prescription orders: A quasi
      experimental study in Iran.
AB  - Background: One way to reduce medical errors associated with physician orders is
      computerized physician order entry (CPOE) software. This study was conducted to
      compare prescription orders between 2 groups before and after CPOE implementation
      in a hospital. Methods: We conducted a before-after prospective study in 2
      intensive care unit (ICU) wards (as intervention and control wards) in the
      largest tertiary public hospital in South of Iran during 2014 and 2016. All
      prescription orders were validated by a clinical pharmacist and an ICU physician.
      The rates of ordering the errors in medical orders were compared before (manual
      ordering) and after implementation of the CPOE. A standard checklist was used for
      data collection. For the data analysis, SPSS Version 21, descriptive statistics,
      and analytical tests such as McNemar, chi-square, and logistic regression were
      used. Results: The CPOE significantly decreased 2 types of errors, illegible
      orders and lack of writing the drug form, in the intervention ward compared to
      the control ward (p< 0.05); however, the 2 errors increased due to the defect in
      the CPOE (p< 0.001). The use of CPOE decreased the prescription errors from 19%
      to 3% (p= 0.001), However, no differences were observed in the control ward
      (p<0.05). In addition, more errors occurred in the morning shift (p< 0.001).
      Conclusion: In general, the use of CPOE significantly reduced the prescription
      errors. Nonetheless, more caution should be exercised in the use of this system,
      and its deficiencies should be resolved. Furthermore, it is recommended that CPOE
      be used to improve the quality of delivered services in hospitals.

PMID- 29445700
TI  - Health care expenditure in the Islamic Republic of Iran versus other high
      spending countries.
AB  - Background: In all countries, health expenditures are a main part of government
      expenditure, and governments try to find policies and strategies to reduce this
      expenditure. Overall expenditure index has been raised 30 times during the past
      20 years in Iran, while in the health sector, the growth in health expenditures
      index has been 71 times. The present study aimed at examining health care
      expenditure in the Islamic Republic of Iran versus other high spending countries.
      Methods: A comparative panel study was conducted in selected countries with the
      high mean of health expenditure per capita. Data were collected from the WORLD
      BANK. Out- of- pocket (OOP), health expenditure per capita, public and private
      health expenditure, and total health expenditure were compared among the selected
      counties. Results: Iran has the lowest health expenditure per capita compared to
      other countries and the USA has the highest health expenditures per capita. In
      Iran, out- of- pocket expenditure, with more than 50%, was the most cost, while
      in Luxembourg it was the least cost during 2004 to 2014, with less than 12%.
      Conclusion: Our findings revealed that politicians and health care executives
      should find a stable source to finance the health system. Stable sources of
      financing lead to having a steady trend in health expenditure.

PMID- 29445699
TI  - Out-of-pocket and informal payments in Iran's health care system: A systematic
      review and meta-analysis.
AB  - Background: Out-of-pocket and informal payments are considered as 2 most
      important topics for equity in health care financing. Therfore, this study was
      conducted to systematically review and meta-analyze the status of these payments
      in Iran's health care system. Methods: Required data were collected through
      searching the following key terms: "Unofficial", "Informal Payment", "Iran",
      "Health Financing", "Health expenditure", and "Out-of-pocket" on Scopus, PubMed,
      IranMedex, SID, and Google Scholar databases. After extracting and screening
      previous studies, data were collected from the articles using PRISMA pattern. To
      perform the metaanalysis, Comprehensive Meta-Analysis (CMA: 2) software was used.
      Results: A total of 15 studies were entered in this review. Overall, the rate of
      out-of-pocket payments was estimated to be 50% (95% CI: 45-57%). A significant
      correlation was found between gender and the rate of out-of-pocket payments
      (p<=0.05). Moreover, the overall rate of informal payments was found to be 35%.
      Most of the informal payments were in form of cash, and the main reasons for
      informal payments were appreciating the staff and medical team as well as
      requests made by the hospital staff. Length of stay, marital status, employment
      status, income, and insurance coverage were key factors in the field of informal
      payments. Conclusion: According to the results of the present study, out-of
      pocket and informal payments are more prevalent in Iran. Considering the negative
      effects of these payments on the health care system, it is of prime importance to
      implement extensive interventions to reduce or even prevent these payments.

PMID- 29445701
TI  - The impact of the learning contract on self-directed learning and satisfaction in
      nursing students in a clinical setting.
AB  - Background: The most important responsibilities of an education system are to
      create self-directed learning opportunities and develop the required skills for
      taking the responsibility for change. The present study aimed at determining the
      impact of a learning contract on self-directed learning and satisfaction of
      nursing students. Methods: A total of 59 nursing students participated in this
      experimental study. They were divided into six 10-member groups. To control the
      communications among the groups, the first 3 groups were trained using
      conventional learning methods and the second 3 groups using learning contract
      method. In the first session, a pretest was performed based on educational
      objectives. At the end of the training, the students in each group completed the
      questionnaires of self-directed learning and satisfaction. The results of
      descriptive and inferential statistical methods (dependent and independent t
      tests) were presented using SPSS. Results: There were no significant differences
      between the 2 groups in gender, grade point average of previous years, and
      interest toward nursing. However, the results revealed a significant difference
      between the 2 groups in the total score of self-directed learning (p= 0.019).
      Although the mean satisfaction score was higher in the intervention group, the
      difference was not statistically significant. Conclusion: This study suggested
      that the use of learning contract method in clinical settings enhances self
      directed learning among nursing students. Because this model focuses on
      individual differences, the researcher highly recommends the application of this
      new method to educators.

PMID- 29445702
TI  - Validity and reliability of Persian version of Listening Styles Profile-Revised
      (LSP- R) in Iranian students.
AB  - Background: Individuals' listening styles differs based on their characters,
      professions and situations. This study aimed to assess the validity and
      reliability of Listening Styles Profile- Revised (LSP- R) in Iranian students.
      Methods: After translating into Persian, LSP-R was employed in a sample of 240
      medical and nursing Persian speaking students in Iran. Statistical analysis was
      performed to test the reliability and validity of the LSP-R. Results: The study
      revealed high internal consistency and good test-retest reliability for the
      Persian version of the questionnaire. The Cronbach's alpha coefficient was 0.72
      and intra-class correlation coefficient 0.87. The means for the content validity
      index and the content validity ratio (CVR) were 0.90 and 0.83, respectively.
      Exploratory factor analysis (EFA) yielded a four-factor solution accounted for
      60.8% of the observed variance. Majority of medical students (73%) as well as
      majority of nursing students (70%) stated that their listening styles were task
      oriented. Conclusion: In general, the study finding suggests that the Persian
      version of LSP-R is a valid and reliable instrument for assessing listening
      styles profile in the studied sample.

PMID- 29445703
TI  - Critical appraisal of fundamental items in approved clinical trial research
      proposals in Mashhad University of Medical Sciences.
AB  - Background: Writing, designing, and conducting a clinical trial research proposal
      has an important role in achieving valid and reliable findings. Thus, this study
      aimed at critically appraising fundamental information in approved clinical trial
      research proposals in Mashhad University of Medical Sciences (MUMS) from 2008 to
      2014. Methods: This cross-sectional study was conducted on all 935 approved
      clinical trial research proposals in MUMS from 2008 to 2014. A valid and reliable
      as well as comprehensive, simple, and usable checklist in sessions with
      biostatisticians and methodologists, consisting of 11 main items as research
      tool, were used. Agreement rate between the reviewers of the proposals, who were
      responsible for data collection, was assessed during 3 sessions, and Kappa
      statistics was calculated at the last session as 97%. Results: More than 60% of
      the research proposals had a methodologist consultant, moreover, type of study or
      study design had been specified in almost all of them (98%). Appropriateness of
      study aims with hypotheses was not observed in a significant number of research
      proposals (585 proposals, 62.6%). The required sample size for 66.8% of the
      approved proposals was based on a sample size formula; however, in 25% of the
      proposals, sample size formula was not in accordance with the study design. Data
      collection tool was not selected appropriately in 55.2% of the approved research
      proposals. Type and method of randomization were unknown in 21% of the proposals
      and dealing with missing data had not been described in most of them (98%).
      Inclusion and exclusion criteria were (92%) fully and adequately explained.
      Moreover, 44% and 31% of the research proposals were moderate and weak in rank,
      respectively, with respect to the correctness of the statistical analysis
      methods. Conclusion: Findings of the present study revealed that a large portion
      of the approved proposals were highly biased or ambiguous with respect to
      randomization, blinding, dealing with missing data, data collection tool,
      sampling methods, and statistical analysis. Thus, it is essential to consult and
      collaborate with a methodologist in all parts of a proposal to control the
      possible and specific biases in clinical trials.

PMID- 29445704
TI  - Prevalence of depression in people with HIV and AIDS in Iran: A systematic
      review.
AB  - Background: Depression is the most common mental disorder in individuals with HIV
      and AIDS (PLWHA), and comorbidity with depression exacerbates the disease.
      Several studies have estimated the prevalence of depression in HIV and AIDS
      patients so far, but there is no consensus about the prevalence of depression
      among these patients. Thus, we aimed at estimating the overall prevalence of
      depression among Iranian PLWHA. Methods: The international and national databases
      including Web of Science, Scopus, Medline, Science Direct, MagIran, Scientific
      Information Database (SID), IranMedex, and Medlib were searched until June 2016.
      The quality of included studies was assessed using Newcastle-Ottawa Scale.
      Results: Out of 591 references, 9 cross-sectional studies met the eligibility
      criteria and were included in the review. The lowest and highest reported
      prevalence of depression among people with HIV was 22% (95% CI: (11, 33)) and 76%
      (95% CI: (71, 81)), respectively. Prevalence of depression in people with HIV in
      the north, west, and south of Iran was 45% (95% CI: (23, 67)), 30% (95% CI: (15,
      45)), and 56% (95% CI: (35, 77)), respectively. Prevalence of depression among
      addict and non-addict patients was 25% (95% CI: (21, 30)) and 58% (95% CI: (40,
      77)), respectively. Conclusion: According to the results of this systematic
      review, the prevalence of depression is considerable among Iranian PLWHA.
      Prevalence in the southern regions of Iran is more than the western and northern
      regions of Iran. This evidence may be useful for Iranian health policymakers to
      design suitable preventive and therapeutic interventions in PLWHA to prevent and
      control depression among these people in Iran.

PMID- 29445705
TI  - Evidence- based medicine performance among health care providers in Iranian
      hospitals: A nationwide survey.
AB  - Background: Evidence- Based Medicine (EBM) refers to the ability and skill in the
      use and integration of the best evidence obtained from repeatable bias-free
      clinical trials with the patients' preferences and conditions. Considering this
      fact that few large-scale studies have been done in this field in Iran, the
      present study aimed at comprehensively reviewing the status of EBM performance
      among health care providers in Iranian hospitals. Methods: This cross-sectional
      study was conducted during 2014 and 2015. Study participants consisted of 2800
      health care providers (physicians, nurses, midwives, and paramedical personnel)
      in active hospitals in Iran. Data collection tool was a self-made questionnaire.
      Content validity of the questionnaire was improved by comments of 10 experts. The
      reliability of the questionnaire was assessed using test-retest method (alpha=
      0.85). Results: The results revealed that only 12.7% and 15.8% of the
      participants were highly familiar with EBM databases and terminologies,
      respectively. Most participants believed that EBM-related workshops and practical
      involvement in EBM-related programs and activities can have a more effect on the
      improvement of EBM performance. Most participants had a positive view of the EBM.
      About 47% of the participants reported that their EBM knowledge and skills is
      high. Among the demographic variables, there were only significant relationships
      between work experience and attitude, gender and attitudes, and between knowledge
      and skills (p<0.05). Conclusion: According to the results of the present study,
      it seems that holding EBM-related workshops and practical participation in EBP
      related programs and activities as well as improving facilities such as manpower,
      equipment, and access can have a significant effect on improving EBM- related
      activities.

PMID- 29445706
TI  - Estimation of economic burden of preterm and premature births in Iran.
AB  - Background: Tremendous difficulties are imposed on families with preterm and
      premature babies, both at birth and during their lifetime. The present study
      aimed at evaluating the potential economic impact of preterm and premature birth
      in Iran. Methods: In this descriptive cross-sectional study (2014-2015), we
      studied preterm and premature newborns, who have been subjected to
      hospitalization in Ali-Asghar hospital. We followed social perspective to
      estimate the economic consequences of preterm and premature birth in 3 categories
      of direct medical, direct non-medical, and indirect costs. Required data were
      collected from documents in the NICU, and studying medical records, and
      interviewing their parents. Data were analyzed by Microsoft Excel. Results:
      Direct medical, direct non-medical and indirect affairs were 84%, 6%, and 10% of
      the total cost, respectively. The estimated social costs were 373, 529, 189; 508,
      774, 181; and 529, 481, 996 US dollars (according to their corresponding
      incidence of 5.8%, 7.9%, and 9.9%). We also found that 75% of the direct medical
      costs of initial hospitalization were due to intensive care beds. Conclusion: The
      economic burden of preterm and premature birth in Iran is considerable and to
      decrease the costs, it is necessary to implement preventive programs for preterm
      and premature newborns and to provide management care and support for families
      dealing with this problem.

PMID- 29445707
TI  - Patient waiting time in hospital emergency departments of Iran: A systematic
      review and meta-analysis.
AB  - Background: Waiting time in emergency department is a key indicator in measuring
      the quality of hospital services and has a significant impact on patient
      satisfaction The purpose of this study was to conduct a systematic review and
      meta-analysis of the patients' waiting time in hospital emergency departments in
      Iran. Methods: Data were collected from databases of Web of Science, Embase,
      PubMed, Scopus, Google scholar, SID, and Iran Medex using the following key
      words: "emergency ward", "emergency room", "waiting time", " time delay", "first
      visit", "first treatment" , "emergency department", "Iran", and their Persian
      equivalents. The timeframe of 2000 to 2016 was selected to search the articles.
      CMA 2 (Comprehensive Meta-Analysis) software was used in this meta-analysis.
      Results: A total of 236 articles were extracted from databases and other sources,
      and finally 17 articles were included in the analysis. In total, waiting time in
      different parts of the emergency department was measured for 15 943 patients.
      Mean+/-SD waiting time was 5.9 +/- 0.6 minutes from the arrival to the first
      visit by a physician, it was 45 +/- 5 minutes between the first visit and the
      first therapeutic steps, 94+/- 33.9 minutes between referring to the laboratory
      and receiving the result, 23.2 +/- 3 minutes between referring to the radiology
      and receiving the result, and 32.2 +/- 7 minutes between referring to ECG and
      receiving the result; moreover, waiting time for the first specialist
      consultation was 99.3 +/- 32.8 minutes. Conclusion: The results demonstrated that
      waiting time in the emergency rooms of Iranian hospitals was higher than the
      national and international standards. According to the high rate of heterogeneity
      in the results and probability of publication bias, we highly recommend that
      readers use the results of this study and pay sufficient attention to this issue.

PMID- 29445708
TI  - Roles of triglyceride and phosphate in atherosclerosis of diabetic hemodialysis
      patients.
AB  - Background: A growing number of patients with End-Stage Renal Disease (ESRD) are
      undergoing long-term hemodialysis (HD). HD needs a vascular access (VA) and
      complications of VA account for a sizable proportion of its costs. One of the
      important cardiovascular diseases (CVD) is atherosclerosis, which is a major
      cause of premature deaths in the world. So, it is essential to find the risk
      factors to treat them before they cause an obvious CVD. Methods: We analyzed data
      from 174 ESRD patients who were candidate for Arterio Venous Fistula (AVF)
      creation from April 2008 to March 2009 in Hasheminejad Kidney Center by
      convenient sampling. X-ray images were used and C 4.5 algorithm of data mining
      techniques revealed the roles of two risk factors for atherosclerosis of diabetic
      ESRD patients. Pearson coefficient was also used to measure the correlation
      between the parameters. Results: Diabetic patients had significantly more
      calcified arteries in their forearm X-ray than other patients (p<0.001).
      Occurrence of atherosclerotic CVD in diabetic HD patients has an adverse relation
      compared with the controlled levels of their plasma levels of Triglyceride (TG)
      and Phosphorus. We found an inverse effect of TG and phosphorus plasma levels on
      the atherosclerotic involvement of radial and ulnar arteries in diabetic HD
      patients. We observed that the prevalence of radial and ulnar arteries
      calcification in these patients is lower when they have higher plasma levels of
      TG and phosphorous. Conclusion: This study investigates the role of high plasma
      levels of TG and phosphorous in the development of atherosclerosis in diabetic HD
      patients. Although many studies showed that hypertriglyceridemia plays a
      promoting role in the development of CVD, our study also found an inverse effect
      of plasma levels of TG on the atherosclerotic involvement of radial and ulnar
      arteries in diabetic patients, and therefore our results support this suspicion
      that hypertriglyceridemia plays a significant role in developing atherosclerosis.

PMID- 29445710
TI  - Ionizing Radiation and Human Gender Proportion at Birth: A Concise Review of the
      Literature and A Complementary Analysis of Historical and Recent Data.

PMID- 29445709
TI  - Association between the circulating leptin levels and the biomarkers of oxidative
      stress and inflammation among Iranian overweight and obese adults.
AB  - Background: Oxidative stress in obese people is an important pathogenic mechanism
      of an obesity-associated metabolic syndrome. We evaluated the association between
      circulating leptin levels with biomarkers of oxidative stress in overweight and
      obese participants. Methods: This study was performed on 189 overweight and obese
      people aged 18-60 years old. Serum leptin, superoxide dismutase (SOD), high
      sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy), thiobarbituric acid
      reactive substances (TBARS) and amyloid A (SAA) concentrations were measured.
      Pearson correlation and multiple linear regressions were used to assess the
      relationships. Results: We found that among the biomarkers of oxidative stress
      and inflammation in participants, serum hs-CRP and SAA were positively correlated
      with BMI (beta=0.003, P<0.001 and beta=7.83, P<0.001, respectively). This
      relationship remained significant even after controlling other oxidative stress
      and inflammatory indicators (beta=0.003, p<0.001 for hs-CRP), but this
      association disappeared for SAA. In addition, serum hs-CRP was positively
      correlated with leptin (beta=0.001, p=0.003). Regression analysis showed that
      there was no association between serum Hcy, SAA, TBARS and SOD with serum leptin
      concentrations Conclusion: Overall, the current study demonstrated that serum hs
      CRP and SAA levels were independently correlated with BMI. Furthermore, serum hs
      CRP was positively correlated with leptin. Focusing on such strategies may lead
      to promises for alleviating obesity and its co-morbidities.

PMID- 29445712
TI  - Radioprotective Effects of Sulfur-containing Mineral Water of Ramsar Hot Spring
      with High Natural Background Radiation on Mouse Bone Marrow Cells.
AB  - Background: We intend to study the inhibitory effect of sulfur compound in Ramsar
      hot spring mineral on tumor-genesis ability of high natural background radiation.
      Objective: The radioprotective effect of sulfur compounds was previously shown on
      radiation-induced chromosomal aberration, micronuclei in mouse bone marrow cells
      and human peripheral lymphocyte. Ramsar is known for having the highest level of
      natural background radiation on Earth. This study was performed to show the
      radioprotective effect of sulfur-containing Ramsar mineral water on mouse bone
      marrow cells. Method: Mice were fed three types of water (drinking water, Ramsar
      radioactive water containing sulfur and Ramsar radioactive water whose sulfur was
      removed). Ten days after feeding, mice were irradiated by gamma rays (0, 2 and 4
      Gy). 48 and 72 hours after irradiating, mice were killed and femurs were removed.
      Frequency of micronuclei was determined in bone marrow erythrocytes. Results: A
      significant reduction was shown in the rate of micronuclei polychromatic
      erythrocyte in sulfur-containing hot spring water compared to sulfur-free water
      in hot spring mineral water. Gamma irradiation induced significant increases in
      micronuclei polychromatic erythrocyte (MNPCE) and decreases in polychromatic
      erythrocyte/polychromatic erythrocyte + normochromatic erythrocyte ratio
      (PCEs/PCEs+NCEs) (P < 0.001) in sulfur-containing hot spring water compared to
      sulfur-free hot spring mineral water. Also, apparently there was a significant
      difference between drinking water and sulfur-containing hot spring water in
      micronuclei polychromatic erythrocyte and polychromatic erythrocyte/polychromatic
      erythrocyte+ normochromatic erythrocyte ratio. Conclusion: The results indicate
      that sulfur-containing mineral water could result in a significant reduction in
      radiation-induced micronuclei representing the radioprotective effect of sulfur
      compounds.

PMID- 29445711
TI  - In-vitro Study of Photothermal Anticancer Activity of Carboxylated Multiwalled
      Carbon Nanotubes.
AB  - Background and Objective: Multi-walled Carbon Nano Tubes (MWCNTs) as an important
      element of nanosciences have a remarkable absorption in the region of NIR window
      (650-900 nm) which can overcome the limitations of deep treatment in photothermal
      therapy. To disperse MWCNTs in water, it is proposed to attach carboxylated
      functional group (-COOH) to MWCNTs in order to increase dispersivity in water.
      Materials and Methods: A stable suspension of MWCNTs-COOH with different
      concentrations (from 2.5 to 500 MUg/ml) was prepared. Then, they were compared
      for their ability to increase temperature in the presence of 810 nm laser
      irradiation and through a wide range of radiation time (from 20 to 600 s) and
      three laser powers (1.5, 2 and 2.5 w). The temperature rise was recorded real
      time every 20 seconds by a precise thermometer. Results: Absorption spectrum of
      MWCNTs-COOH suspension was remarkably higher than water in a wavelength range of
      200 to 1100 nm. For example, using the concentrations of 2.5 and 80 MUg/ml of
      MWCNTs-COOH suspension caused a temperature elevation 2.35 and 9.23 times
      compared to water, respectively, upon 10 min laser irradiation and 2.5 w.
      Moreover, this predominance can be observed for 1.5 and 2 w radiation powers,
      too. Our findings show that the maximum of temperature increase was obtained at
      80 MUg/ml concentration of MWCNT-COOH suspension for three powers and through all
      periods of exposure time. Our results show that the minimum required parameters
      for a 5 degrees C temperature increase (a 5 degrees C temperature increase causes
      cell death) were achieved through 2.5 w, 28 MUg/ml concentration and 20 second
      irradiation time in which both concentration and radiation times were relatively
      low. Conclusion: Our results showed that MWCNTs-COOH can be considered as a
      potent photothermal agent in targeted therapies. New strategies must be developed
      to minimize the concentration, irradiation time and radiation power used in
      experiments.

PMID- 29445713
TI  - Effects of Laser Physical Parameters on Lesion Size in Retinal Photocoagulation
      Surgery: Clinical OCT and Experimental Study.
AB  - Introduction: The aim of the present study was to determine burn intensity in
      retinal laser photocoagulation based on laser parameters; wavelength, power, beam
      size and pulse duration, using Optical Coherence Tomography (OCT), fundus camera,
      physical eye model and computer simulation in a clinical study. Materials and
      Methods: Participants were 10 adult patients between 50-80 years with
      proliferative diabetic retinopathy. A multicolor-photo coagulator with 532 nm
      green and 672 nm red for retina photocoagulation in diabetic retinopathy was used
      to investigate the participants. Lesion size was measured for spot sizes 50 and
      100 MUm, with 100 and 150 mW laser power, and pulse duration 50 and 100 ms by
      OCT. Artificial eye and Zemax-optical design software were used with the same
      laser parameters. Results: Appearance of OCT and fundus images showed direct
      relationship between retina burn size and lesion intensity with exposure time and
      power and also reverse relationship with laser spot size. Compared to red
      wavelength, burn size and lesion intensity increased in green wavelength. On the
      other hand, results from physical eye model were the same as clinical examination
      shown. Laser spot size in retina with Zemax simulation demonstrated that red
      wavelength was greater than green one. Conclusion: This study showed shorter
      pulses provide decrease in duration of laser surgery with significantly reduced
      pain. Results and calculations described in this article can help clinicians
      adjusting the required total coagulated area, the number of lesions and pattern
      density.

PMID- 29445714
TI  - Brain Volume Estimation Enhancement by Morphological Image Processing Tools.
AB  - Background: Volume estimation of brain is important for many neurological
      applications. It is necessary in measuring brain growth and changes in brain in
      normal/abnormal patients. Thus, accurate brain volume measurement is very
      important. Magnetic resonance imaging (MRI) is the method of choice for volume
      quantification due to excellent levels of image resolution and between-tissue
      contrast. Stereology method is a good method for estimating volume but it
      requires to segment enough MRI slices and have a good resolution. In this study,
      it is desired to enhance stereology method for volume estimation of brain using
      less MRI slices with less resolution. Methods: In this study, a program for
      calculating volume using stereology method has been introduced. After morphologic
      method, dilation was applied and the stereology method enhanced. For the
      evaluation of this method, we used T1-wighted MR images from digital phantom in
      BrainWeb which had ground truth. Results: The volume of 20 normal brain extracted
      from BrainWeb, was calculated. The volumes of white matter, gray matter and
      cerebrospinal fluid with given dimension were estimated correctly. Volume
      calculation from Stereology method in different cases was made. In three cases,
      Root Mean Square Error (RMSE) was measured. Case I with T=5, d=5, Case II with
      T=10, D=10 and Case III with T=20, d=20 (T=slice thickness, d=resolution as
      stereology parameters). By comparing these results of two methods, it is obvious
      that RMSE values for our proposed method are smaller than Stereology method.
      Conclusion: Using morphological operation, dilation allows to enhance the
      estimation volume method, Stereology. In the case with less MRI slices and less
      test points, this method works much better compared to Stereology method.

PMID- 29445715
TI  - Detection of Ultraweak Photon Emission (UPE) from Cells as a Tool for
      Pathological Studies.
AB  - Objective: It is well-known that all living cells emit ultra-weak photon emission
      (UPE), which is due to byproducts of chemical reactions in cell metabolisms. It
      has been shown that Reactive Oxygen Species (ROS) in the cells enhances the UPE
      intensity. The magnitude of such UPE is extremely weak (i.e. a few to 103
      photons/ (sec.cm22)), and the detection of such ultra-weak signals is hardly
      possible via sensitive instruments like photomultiplier tube (PMT) that can
      detect single photons. Materials and Methods: H2O2 factor with various
      concentrations was applied on the HT-29 cells to generate ROS. H2O2
      concentrations were so low to be nondestructive to the cells. Then, the effect of
      ROS generation on UPE intensity was investigated. PMT was used to detect UPE from
      HT-29 cells. Results: The topical application of H2O2 was significantly different
      (P < 0.05) in comparison with HT-29 cells without H2O2 at a concentration of 1mM
      in 5 min detection time. The integrated UPE in the presence of H2O2 at
      concentration of 3mM was significantly higher (P < 0.05) than the integrated UPE
      in other groups at the same detection time. The difference between the
      concentrations of 3mM and 4mM was not significant (P > 0.01) for integrated UPE
      in the cell groups in the presence of H2O2. Conclusion: The results show that the
      recorded UPE from HT-29 cells increased with the topical application of exogenous
      ROS inducer. As a result, UPE can be used as a non-invasive technique for
      monitoring ROS in cells.

PMID- 29445716
TI  - A Study on Performance and Safety Tests of Defibrillator Equipment.
AB  - Introduction: Nowadays, more than 10,000 different types of medical devices can
      be found in hospitals. This way, medical electrical equipment is being employed
      in a wide variety of fields in medical sciences with different physiological
      effects and measurements. Hospitals and medical centers must ensure that their
      critical medical devices are safe, accurate, reliable and operational at the
      required level of performance. Defibrillators are critical resuscitation devices.
      The use of reliable defibirillators has led to more effective treatments and
      improved patient safety through better control and management of complications
      during Cardiopulmonary Resuscitation (CPR). Materials and Methods: The
      metrological reliability of twenty frequent use, manual defibrillators in use ten
      hospitals (4 private and 6 public) in one of the provinces of Iran according to
      international and national standards was evaluated. Results: Quantitative
      analysis of control and instrument accuracy showed the amount of the obtained
      results in many units are critical which had less value over the standard
      limitations especially in devices with poor battery. For the accuracy of
      delivered energy analysis, only twelve units delivered acceptable output values
      and the precision in the output energy measurements especialy in weak battry
      condition, after activation of discharge alarm, were low. Conclusion: Obtained
      results indicate a need for new and severe regulations on periodic performance
      verifications and medical equipment quality control program especially for high
      risk instruments. It is also necessary to provide training courses on the
      fundumentals of operation and performane parameters for medical staff in the
      field of meterology in medicine and how one can get good accuracy results
      especially in high risk medical devices.

PMID- 29445717
TI  - Acceptance of Health Information Technologies, Acceptance of Mobile Health: A
      Review Article.
AB  - Background: Mobile health is one of the new technologies for the utilization of
      health information. For its successful implementation as well as any other
      system, we must primarily measure the adoption and use of its factors. The
      purpose of this study was to systematically investigate published articles about
      the factors affecting the adoption of mobile health and categorizing the factors
      affecting the adoption of this system. Methods: This study is a comprehensive
      review done by searching major databases such as Google Scholar, Emerald, Science
      Direct, Iran Medex, SID, Magiran, Pub med, etc. In addition, we use Mobile,
      mobile Health + adoption, mobile Health + TAM, Health + TAM keywords in the range
      of 2004 to 2015. Results: Among the studies that use information technology
      theories to survey the factors affecting the adoption of mobile health, TAM model
      was used more than other models. Factors such as perceived ease of use, perceived
      usefulness and facilitating condition form TUATU are the most effective in the
      adoption of mobile health. Conclusion: Results showed that by considering factors
      such as perceived ease of use, perceived usefulness and facilitating condition
      can increase the adoption of mobile health system. Consequently, these factors
      are recommended to be considered in planning to run systems.

PMID- 29445718
TI  - Designing and Developing Automatic Trolley for Washing and Dressing the Wounds.
AB  - Introduction: Many items are needed for dressing including sterile dressing set,
      antiseptic and washing solutions, leucoplast tape, waste bin for infectious
      garbage, waste bin for noninfectious garbage, safe disposal trash for sharp
      cutting instruments, bedpan and sometimes drugs. All the items are laid out on a
      simple wheeled trolley. The multiplicity of items together with problems in
      placing tools on trolley, forgetting some items, disturbing sterile condition,
      falling and damaging equipment and the need for at least two people for each
      procedure, all are the reasons to design and develop Automatic Trolley for
      Washing and Dressing the Wounds. Material and Method: To develop a mobile unit
      which meets our needs for dressing, the trolley patents registered in America and
      different companies were evaluated as well as the materials and methods used
      while dressing were considered. Results: Automatic Trolley for Washing and
      Dressing the Wounds was designed and developed. It comprises the followings:
      drawer, waste bin for infectious garbage, waste bin for noninfectious garbage,
      shelves for serum and betadine solution, serum stand, peristaltic pump, flexible
      tube for connecting serum, a place for bedpan, foot pedal for serum flow, two eye
      sensor chambers for solution betadine and scrub, an auxiliary work surface.
      Conclusion: Due to the usual requirements for dressing, we have designed an
      equipped mobile unit which covers all the objectives of dressing and increases
      the speed of procedure. Moreover, due to the contrived equipment on the trolley,
      procedures are done quickly and second person is not required to assist.
      Automatic Trolley for Washing and Dressing the Wounds is made up of stainless
      steel which could be mass housing and commercializing which would play a
      deserving role in improving the fundamentals of health care and wound treatment.

PMID- 29445719
TI  - Corrigendum to "Advanced Hepatic Fibrosis in Fatty Liver Disease Linked to
      Hyperplastic Colonic Polyp".
AB  - [This corrects the article DOI: 10.1155/2017/2054871.].

PMID- 29445721
TI  - Young Adults' Selection and Use of Dependent Coverage under the Affordable Care
      Act.
AB  - The dependent coverage expansion under the Affordable Care Act (ACA) required
      health insurance policies that cover dependents to offer coverage for
      policyholder' children up to age 26. It has been well documented that the
      provision successfully reduced the uninsured rate among the young adults.
      However, less is known about whether dependent coverage crowded out other
      insurance types and whether young adults used dependent coverage as a fill-in-the
      gap short-term option. Using data from the Survey of Income and Program
      Participation 2008 Panel, the paper assesses dependent coverage uptake and
      duration before and after the ACA provision among young adults aged 19-26 versus
      those aged 27-30. Regressions for additional coverage outcomes were also
      performed to estimate the crowd-out rate. It was found that the ACA provision had
      a significant positive impact on dependent coverage uptake and duration. The
      estimated crowd-out rate ranges from 27 to 42%, depending on the definition. Most
      dependent coverage enrollees used the coverage for 1 or 2 years. Differences in
      dependent coverage uptake and duration remained among racial groups. Less healthy
      individuals were also less likely to make use of dependent coverage.

PMID- 29445722
TI  - Genetic Testing between Private and Public Interests: Some Legal and Ethical
      Reflections.
AB  - In Europe, there is a wide variety of genetic tests that various private
      companies offer to patients or to consumers. More and more people have become
      curious about their genetic predisposition and susceptibility. Most public health
      care systems, however, are not adequately prepared for responding to these new
      demands and to the results of these genetic tests as, quite often, there is no
      available therapy for the identified genetic condition. This discrepancy between
      the newly emerging expectations and the insufficient responses contributes to a
      further rift between the public and private sectors of health care. Individual
      genetic test results may also trigger the need for personalized medicine and may
      open up a competition between the two fields in offering further genetic tests
      and medical exams. Pro-active patients may need a different kind of information
      on genetic tests and their implications. In this context, how should the public
      health system deal with the challenges of private testing? Will private genetic
      testing transform health care from a solidarity-based system to an
      individualistic one? In this paper, I would like to explore the emerging legal
      and ethical issues related to genetic testing and the relevant legal framework
      that has developed so far. In the conclusion, I will examine the possibilities of
      further legal development.

PMID- 29445723
TI  - Cord Care Practices: A Perspective of Contemporary African Setting.
AB  - Background: Cord care is the series of steps applied in handling of the umbilical
      cord after delivery of the new born. Globally, an estimated 4 million deaths
      occur annually within the first 4 weeks of life and 1.5 million of these deaths
      are attributable to infections. In Nigeria, studies have reported umbilical cord
      infections accounting for between 10 and 19% of neonatal admissions and resultant
      estimated 30-49% neonatal deaths. Hence, this study was conducted to assess the
      knowledge and practice of cord care within a contemporary setting. Methodology:
      This was a cross-sectional study conducted among 324 mothers of children less
      than 59 months using a multistage sampling technique and SSPS version 20 was used
      for data analysis. Crude and adjusted odds ratios as well as 95% confidence
      interval were used in this study with a P-value of <=0.05 considered
      statistically significant. Results: The mean age of the mothers in the study was
      27.5 +/- 6 years with majority of them having good overall knowledge and practice
      of cord care. Factors such residence in rural community (AOR = 0.26; 95% CI =
      0.0915-0.7230) and heath facility delivery (AOR = 7.0; 95% CI = 4.7877-9.3948)
      were predictors of cord care practices. Conclusion: This study has brought to
      light the level of cord care practices with health facility delivery, place of
      residence, and knowledge of cord care as its determinants.

PMID- 29445720
TI  - Application of Single-Nucleotide Polymorphism-Related Risk Estimates in
      Identification of Increased Genetic Susceptibility to Cardiovascular Diseases: A
      Literature Review.
AB  - Background: Although largely preventable, cardiovascular diseases (CVDs) are the
      biggest cause of death worldwide. Common complex cardiovascular disorders (e.g.,
      coronary heart disease, hypertonia, or thrombophilia) result from a combination
      of genetic alterations and environmental factors. Recent advances in the genomics
      of CVDs have fostered huge expectations about future use of susceptibility
      variants for prevention, diagnosis, and treatment. Our aim was to summarize the
      latest developments in the field from a public health perspective focusing on the
      applicability of data on single-nucleotide polymorphisms (SNPs), through a
      systematic review of studies from the last decade on genetic risk estimating for
      common CVDs. Methods: Several keywords were used for searching the PubMed,
      Embase, CINAHL, and Web of Science databases. Recent advances were summarized and
      structured according to the main public health domains (prevention, early
      detection, and treatment) using a framework suggested recently for translational
      research. This framework includes four recommended phases: "T1. From gene
      discovery to candidate health applications; T2. From health application to
      evidence-based practice guidelines; T3. From evidence-based practice guidelines
      to health practice; and T4. From practice to population health impacts." Results:
      The majority of translation research belongs to the T1 phase "translation of
      basic genetic/genomic research into health application"; there are only a few
      population-based impacts estimated. The studies suggest that an SNP is a poor
      estimator of individual risk, whereas an individual's genetic profile combined
      with non-genetic risk factors may better predict CVD risk among certain patient
      subgroups. Further research is needed to validate whether these genomic profiles
      can prospectively identify individuals at risk to develop CVDs. Several research
      gaps were identified: little information is available on studies suggesting
      "Health application to evidence-based practice guidelines"; no study is available
      on "Guidelines to health practice." It was not possible to identify studies that
      incorporate environmental or lifestyle factors in the risk estimation.
      Conclusion: Currently, identifying populations having a larger risk of developing
      common CVDs may result in personalized prevention programs by reducing people's
      risk of onset or disease progression. However, limited evidence is available on
      the application of genomic results in health and public health practice.

PMID- 29445724
TI  - Ethical Gambling: A Necessary New Point of View of Gambling in Public Health
      Policies.

PMID- 29445725
TI  - A Polyoxoniobate/g-C3N4 Nanoporous Material with High Adsorption Capacity of
      Methylene Blue from Aqueous Solution.
AB  - A polyoxoniobate/g-C3N4 nanoporous material with functional groups has been
      synthesized by using carbon nitride (g-C3N4) and hexaniobate (K8Nb6O19.10H2O,
      abbreviated as NbO) as precursors. The structure and compositions of the as
      prepared nanomaterials were characterized by XRD, FT-IR, FESEM, TEM, and XPS.
      These two kinds of materials interact with each other forming a hybrid composite,
      which can be used as an adsorbent for removing a cationic dye (methylene blue,
      MB) from wastewater with excellent adsorption capacity. Furthermore, parameters
      that can affect adsorption process including initial dye concentration, pH and
      temperature were investigated by bath adsorption experiments. The results
      indicated that the maximum adsorption capacity of NbO/g-C3N4 can reach up to
      373.1 mg g-1. Moreover, the equilibrium experiment data fitted Langmuir isotherm
      well and the adsorption kinetics showed that the pseudo second order model can
      satisfyingly described MB adsorption kinetics. The thermodynamic analysis
      indicated that the adsorption was endothermic and spontaneous.

PMID- 29445726
TI  - Progressive Hemifacial Atrophy and Linear Scleroderma En Coup de Sabre: A
      Spectrum of the Same Disease?
AB  - Similar clinical and histhopathological features in progressive hemifacial
      atrophy and linear scleroderma en coup de sabre are well known. Trauma may
      predispose to the development of both diseases. The lack of association with anti
      Borrelia antibodies was shown in both cases as well. The otolaryngological and
      endocrine disorders may be associated findings in both diseases. However, there
      are certain differences in neurological and ophthalmological changes in the
      diseases.

PMID- 29445727
TI  - Molecular Features Underlying Selectivity in Chicken Bitter Taste Receptors.
AB  - Chickens sense the bitter taste of structurally different molecules with merely
      three bitter taste receptors (Gallus gallus taste 2 receptors, ggTas2rs),
      representing a minimal case of bitter perception. Some bitter compounds like
      quinine, diphenidol and chlorpheniramine, activate all three ggTas2rs, while
      others selectively activate one or two of the receptors. We focus on bitter
      compounds with different selectivity profiles toward the three receptors, to shed
      light on the molecular recognition complexity in bitter taste. Using homology
      modeling and induced-fit docking simulations, we investigated the binding modes
      of ggTas2r agonists. Interestingly, promiscuous compounds are predicted to
      establish polar interactions with position 6.51 and hydrophobic interactions with
      positions 3.32 and 5.42 in all ggTas2rs; whereas certain residues are responsible
      for receptor selectivity. Lys3.29 and Asn3.36 are suggested as ggTas2r1
      specificity-conferring residues; Gln6.55 as ggTas2r2-specificity-conferring
      residue; Ser5.38 and Gln7.42 as ggTas2r7-specificity conferring residues. The
      selectivity profile of quinine analogs, quinidine, epiquinidine and
      ethylhydrocupreine, was then characterized by combining calcium-imaging
      experiments and in silico approaches. ggTas2r models were used to virtually
      screen BitterDB compounds. ~50% of compounds known to be bitter to human are
      likely to be bitter to chicken, with 25, 20, 37% predicted to be ggTas2r1,
      ggTas2r2, ggTas2r7 agonists, respectively. Predicted ggTas2rs agonists can be
      tested with in vitro and in vivo experiments, contributing to our understanding
      of bitter taste in chicken and, consequently, to the improvement of chicken feed.

PMID- 29445728
TI  - Radiation-Induced Cardiovascular Disease: Mechanisms and Importance of Linear
      Energy Transfer.
AB  - Radiation therapy (RT) in the form of photons and protons is a well-established
      treatment for cancer. More recently, heavy charged particles have been used to
      treat radioresistant and high-risk cancers. Radiation treatment is known to cause
      cardiovascular disease (CVD) which can occur acutely during treatment or years
      afterward in the form of accelerated atherosclerosis. Radiation-induced
      cardiovascular disease (RICVD) can be a limiting factor in treatment as well as a
      cause of morbidity and mortality in successfully treated patients. Inflammation
      plays a key role in both acute and chronic RICVD, but the underling
      pathophysiology is complex, involving DNA damage, reactive oxygen species, and
      chronic inflammation. While understanding of the molecular mechanisms of RICVD
      has increased, the growing number of patients receiving RT warrants further
      research to identify individuals at risk, plans for prevention, and targets for
      the treatment of RICVD. Research on RICVD is also relevant to the National
      Aeronautics and Space Administration (NASA) due to the prevalent space radiation
      environment encountered by astronauts. NASA's current research on RICVD can both
      contribute to and benefit from concurrent work with cell and animal studies
      informing radiotoxicities resulting from cancer therapy. This review summarizes
      the types of radiation currently in clinical use, models of RICVD, current
      knowledge of the mechanisms by which they cause CVD, and how this knowledge might
      apply to those exposed to various types of radiation.

PMID- 29445729
TI  - Brucella Antibodies in Alaskan True Seals and Eared Seals-Two Different Stories.
AB  - Brucella pinnipedialis was first isolated from true seals in 1994 and from eared
      seals in 2008. Although few pathological findings have been associated with
      infection in true seals, reproductive pathology including abortions, and the
      isolation of the zoonotic strain type 27 have been documented in eared seals. In
      this study, a Brucella enzyme-linked immunosorbent assay (ELISA) and the Rose
      Bengal test (RBT) were initially compared for 206 serum samples and a discrepancy
      between the tests was found. Following removal of lipids from the serum samples,
      ELISA results were unaltered while the agreement between the tests was improved,
      indicating that serum lipids affected the initial RBT outcome. For the remaining
      screening, we used ELISA to investigate the presence of Brucella antibodies in
      sera of 231 eared and 1,412 true seals from Alaskan waters sampled between 1975
      and 2011. In eared seals, Brucella antibodies were found in two Steller sea lions
      (Eumetopias jubatus) (2%) and none of the 107 Northern fur seals (Callorhinus
      ursinus). The low seroprevalence in eared seals indicate a low level of exposure
      or lack of susceptibility to infection. Alternatively, mortality due to the
      Brucella infection may remove seropositive animals from the population. Brucella
      antibodies were detected in all true seal species investigated; harbor seals
      (Phoca vitulina) (25%), spotted seals (Phoca largha) (19%), ribbon seals
      (Histriophoca fasciata) (16%), and ringed seals (Pusa hispida hispida) (14%).
      There was a low seroprevalence among pups, a higher seroprevalence among
      juveniles, and a subsequent decreasing probability of seropositivity with age in
      harbor seals. Similar patterns were present for the other true seal species;
      however, solid conclusions could not be made due to sample size. This pattern is
      in accordance with previous reports on B. pinnipedialis infections in true seals
      and may suggest environmental exposure to B. pinnipedialis at the juvenile stage,
      with a following clearance of infection. Furthermore, analyses by region showed
      minor differences in the probability of being seropositive for harbor seals from
      different regions regardless of the local seal population trend, signifying that
      the Brucella infection may not cause significant mortality in these populations.
      In conclusion, the Brucella infection pattern is very different for eared and
      true seals.

PMID- 29445730
TI  - Pilot study of a smartphone application designed to socially motivate
      cardiovascular disease patients to improve medication adherence.
AB  - Background: Social support received by patients from family and community has
      been identified as a key factor for success in improving medication adherence in
      those patients. This pilot study aimed to investigate the usability and
      feasibility of PillPal, a smartphone application that uses video-chatting as a
      social motivation medium to encourage medication adherence in cardiovascular
      disease (CVD) patients. We additionally gathered feedback on the Physician
      Calendar, an accompanying web platform that allows clinicians to view patient
      adherence data generated from the app. Methods: Thirty patients were recruited
      from the Johns Hopkins Hospital (JHH) Lipid Clinic (n=14) and Inpatient
      Cardiology Service (n=16) to pilot test the app. Data were obtained through in
      person interviews in which patients tested out the app and answered standardized
      questions regarding the app's feasibility as a means to enhance social support,
      as well as its usability measured in terms of ease of use and patient comfort
      level with the video-chat technology. Cardiologists (n=10) from JHH were
      interviewed to gain feedback on the Physician Calendar. Results: We recorded
      43.4% participants who stated that PillPal would increase their motivation to
      take their medications; 96.7% stated the app was easy to use; and 70% stated they
      were comfortable with video-chatting while taking their medications. Patient
      factors such as current adherence level, disease severity, and personality were
      more predictive of positive app reviews than the perceived level of social
      support. Clinicians generally approved of the Physician Calendar, as they would
      be able to quickly screen for non-adherence and begin conversations with patients
      to address the root cause of their non-adherence. Conclusions: Based on pilot
      testing and interviews, using a smartphone app for video-chatting as a social
      support medium to improve patient medication adherence is feasible and has
      potential to increase medication adherence depending on certain patient
      characteristics. The Physician Calendar was deemed a useful tool by clinicians to
      quickly identify and understand reasons for medication non-adherence.

PMID- 29445731
TI  - Expecting great expectations when expecting.
AB  - Pregnancy is a time when a woman experiences a number of unexpected biological,
      psychological and social changes. Traditionally, woman sought guidance and help
      from their mothers and/or social circles to learn how to tackle these changes.
      With the advent of the mobile revolution, women are now turning to mobile
      applications to do the same. In this article, we review a pregnancy tracking
      mobile application called Ovia, in the light of the comments made by mothers
      using it from around the world. We learn that women like Ovia because it allows
      them to track, monitor and explore their pregnancy journey by receiving
      personalized guidance.

PMID- 29445732
TI  - Dynamic Changes of Mitochondrial Fusion and Fission in Brain Injury after Cardiac
      Arrest in Rats.
AB  - Mitochondria change their morphology dynamically by continual fusion and fission
      processes to fulfill their function. However, little is known about the effect of
      cardiac arrest on mitochondrial dynamics. This study aimed to investigate time
      dependent change of the mitochondrial dynamics after brain ischemic injury in
      rats of cardiac arrest. After resuscitation, obvious neuronal injury, reduced
      adenosine triphosphate (ATP) levels, excessive reactive oxygen species (ROS)
      generation, decreased mitochondrial membrane potential (MMP), and increased
      release of mitochondrial cytochrome c were observed at 12 h and 24 h after
      cardiac arrest. Moreover, we found that elongation of mitochondria was observed
      at 4 h after cardiac arrest, whereas fragmented mitochondria were significantly
      increased, along with concomitant increase in the fission proteins Drp1 and Fis1
      and a reduction in the fusion proteins Mfn1 and Mfn2 at 12 h and 24 h after
      cardiac arrest. Taken together, these findings suggest that imbalance in
      mitochondrial dynamics probably contributes to brain injury after cardiac arrest.

PMID- 29445733
TI  - Route of Injection Affects the Impact of InlB Internalin Domain Variants on
      Severity of Listeria monocytogenes Infection in Mice.
AB  - The facultative intracellular pathogen Listeria monocytogenes causes a severe
      food-borne infection in humans and animals. L. monocytogenes invasion factor InlB
      interacts with the tyrosine kinase c-Met via the N-terminal internalin domain.
      Previously, distinct variants of the InlB internalin domain (idInlB) have been
      described in L. monocytogenes field isolates. Three variants were used to restore
      full-length InlB expression in the L. monocytogenes strain EGDeDeltainlB.
      Obtained isogenic L. monocytogenes strains were tested in the invasion assay and
      intravenous, intraperitoneal, and intragastric models of infection in mice. All
      idInlBs were functional, restored InlB activity as an invasion factor, and
      improved invasion of the parental strain EGDeDeltainlB into human kidney HEK23
      cells. Meanwhile, distinct idInlBs provided different mortality rates and
      bacterial loads in internal organs. When recombinant strains were compared, the
      variant designated idInlB14 decreased severity of disease caused by intravenous
      and intraperitoneal bacterial administration, whereas this variant improved
      intestine colonization and stimulated intragastric infection. Obtained results
      demonstrated that naturally occurring idInlBs differed in their impact on
      severity of L. monocytogenes infection in mice in dependence on the infection
      route.

PMID- 29445735
TI  - Corrigendum to "Curcumin Analogue CA15 Exhibits Anticancer Effects on HEp-2 Cells
      via Targeting NF-kappaB".
AB  - [This corrects the article DOI: 10.1155/2017/4751260.].

PMID- 29445736
TI  - Tuberculosis Treatment Outcomes and Factors Associated with Each of Them in a
      Cohort Followed Up between 2010 and 2014.
AB  - Tuberculosis treatment has undergone recent changes in Brazil. Objective. To
      assess whether favorable outcomes on tuberculosis therapy improved in recent
      years. Methods. Retrospective observational study, based on primary data of
      tuberculosis patients, followed at INI-FIOCRUZ, from January 2012 to December
      2014. Results. The outcomes observed were as follows: cure (80%), default (14%),
      treatment failure (5%), and death (1%). HIV infection without antiretroviral
      therapy [OR 0.34 (0.15-0.79)], tuberculosis diagnosis based on sputum smear [OR
      0.22 (0.07-0.74)], drug use [OR 0.22 (0.11-0.46)], and/or treatment interruption
      due to adverse reactions [OR 0.23 (0.08-0.67)] decreased the chance of cure.
      Predictors of default, that is, use of noninjecting drugs [OR 3.00 (95% CL 1.31
      6.88)], treatment interruption due to adverse reactions [OR 6.30 (1.81-21.95)],
      low schooling [OR 2.59 (2.15-5.82)], higher age [OR 0.44 (0.23-0.82)], and female
      gender [OR 0.28 (0.11-0.71)], reduced the chance of treatment default.
      Tuberculosis diagnosis based on sputum smear [OR 7.77 (1.94-31.09)] and/or
      arterial hypertension [OR 4.07 (1.25-13.18)] was associated with treatment
      failure. Conclusion. Mortality and default were low considering the prevalence of
      HIV infection; however cure was not significantly increased.

PMID- 29445734
TI  - Failure of the PTEN/aPKC/Lgl Axis Primes Formation of Adult Brain Tumours in
      Drosophila.
AB  - Different regions in the mammalian adult brain contain immature precursors,
      reinforcing the concept that brain cancers, such as glioblastoma multiforme
      (GBM), may originate from cells endowed with stem-like properties. Alterations of
      the tumour suppressor gene PTEN are very common in primary GBMs. Very recently,
      PTEN loss was shown to undermine a specific molecular axis, whose failure is
      associated with the maintenance of the GBM stem cells in mammals. This axis is
      composed of PTEN, aPKC, and the polarity determinant Lethal giant larvae (Lgl):
      PTEN loss promotes aPKC activation through the PI3K pathway, which in turn leads
      to Lgl inhibition, ultimately preventing stem cell differentiation. To find the
      neural precursors responding to perturbations of this molecular axis, we targeted
      different neurogenic regions of the Drosophila brain. Here we show that PTEN
      mutation impacts aPKC and Lgl protein levels also in Drosophila. Moreover, we
      demonstrate that PI3K activation is not sufficient to trigger tumourigenesis,
      while aPKC promotes hyperplastic growth of the neuroepithelium and a noticeable
      expansion of the type II neuroblasts. Finally, we show that these neuroblasts
      form invasive tumours that persist and keep growing in the adult, leading the
      affected animals to untimely death, thus displaying frankly malignant behaviours.

PMID- 29445737
TI  - Effects of TLR3 and TLR9 Signaling Pathway on Brain Protection in Rats Undergoing
      Sevoflurane Pretreatment during Cardiopulmonary Bypass.
AB  - Objective: To investigate the effects of TLR3 and TLR9 signaling pathway on brain
      injury during CPB in rats pretreated with sevoflurane and its possible molecular
      mechanism. Methods: SD rats were randomly assigned to sham group, CPB group, and
      Sev group. Brain tissue was obtained at before CPB (T0), at CPB for 30 minutes
      (T1), 1 hour after CPB (T3), and 3 hours after CPB (T5). ELISA was used to
      measure S100-beta and IL-6. Western blot was utilized to determine TLR3 and TLR9
      expression. TUNEL was applied to detect neuronal apoptosis. Results: Compared
      with CPB group, at T1, at termination after 1 hour of CPB (T2), T3, 2 hours after
      CPB (T4) and T5, S100-beta and IL-6 decreased in Sev group. Compared with CPB
      group, IFN-beta were increased in Sev group, except T0. Compared with CPB group,
      TLR3 expression increased, and TLR9 and NF-kappaB decreased in Sev group. The
      apoptotic neurons were less in Sev group than in CPB group (P < 0.05).
      Conclusion: Sevoflurane intervention can activate TLR3 and TLR9 signaling
      pathway, upregulate TLR3 expression and downstream TRIF expression, decrease TLR9
      expression, and downregulate downstream NF-kappaB expression in CPB rat models,
      thereby mitigating brain injury induced by inflammatory response during CPB.

PMID- 29445738
TI  - Expression of Cancer Stem Cell Marker CD44 and Its Polymorphisms in Patients with
      Chronic Gastritis, Precancerous Gastric Lesion, and Gastric Cancer: A Cross
      Sectional Multicenter Study in Thailand.
AB  - Here we investigated CD44 protein expression and its polymorphisms in patients
      with chronic gastritis, precancerous gastric lesions, and gastric cancer; and we
      evaluated our result with the risk of CD44 protein expression and
      clinicopathological characteristics. Our results obtained by analyzing 162
      gastric cancer patients, 125 chronic gastritis, and 165 precancerous gastric
      lesions from three study centers in Thailand showed that CD44 expression was
      significantly higher in patients with precancerous gastric lesions and gastric
      cancer while patients with chronic gastritis were negative for CD44 staining (p =
      0.036). We further observed the significant association of variant genotype;
      gastric cancer patients carrying AG or GG of CD44 rs187116 had more increased
      risk of CD44 expression than wild-type (WT) carriers (AG: odds ratio (OR) = 5.67;
      95% CI = 1.57-7.23; p = 0.024 and GG: OR = 8.32; 95% CI = 2.94-11.42; p = 0.016),
      but no significant difference in the risk of CD44 expression due to polymorphism
      in patients with precancerous gastric lesions. Our results suggested that CD44
      expression could be used as a marker for the prediction of gastric cancer
      development, particularly in patients with precancerous gastric lesions carrying
      AG or GG, who were selected to surveillance follow-up for gastric cancer
      prevention.

PMID- 29445740
TI  - Correlation between Pathological Characteristics and Young's Modulus Value of
      Spastic Gastrocnemius in a Spinal Cord Injury Rat Model.
AB  - The goal of the present study were (1) to investigate the pathological
      characteristics of gastrocnemius muscle (GM) and quantitatively assess GM tissue
      stiffness in rat models with spinal cord injury (SCI) and (2) to explore the
      correlation between pathological characteristics changes and Young's modulus
      value of GM. 24 Sprague Dawley male rats were allocated into normal control
      groups and SCI model subgroups, respectively. GM stiffness was assessed with
      shear wave sonoelastography technology. All GMs were further analyzed by
      pathological examinations. GM weights were decreased, the ratio of type I fibers
      was decreased, and the ratio of type II fibers was increased in the GM in the
      model group. MyHC-I was decreased, while MyHC-II was increased according to the
      electrophoretic analysis in model subgroups. The elastic modulus value of GM was
      increased in the model group. A significant negative correlation was found
      between Young's modulus value of GM and the ratio of type I fibers of GM in model
      subgroup. Our studies showed that the stiffness of GM is correlated with
      pathological characteristics during the initial stages of SCI in rats. We also
      identified shear wave sonoelastography technology as a useful tool to assess GM
      stiffness in SCI rat models.

PMID- 29445741
TI  - PSBinder: A Web Service for Predicting Polystyrene Surface-Binding Peptides.
AB  - Polystyrene surface-binding peptides (PSBPs) are useful as affinity tags to build
      a highly effective ELISA system. However, they are also a quite common type of
      target-unrelated peptides (TUPs) in the panning of phage-displayed random peptide
      library. As TUP, PSBP will mislead the analysis of panning results if not
      identified. Therefore, it is necessary to find a way to quickly and easily
      foretell if a peptide is likely to be a PSBP or not. In this paper, we describe
      PSBinder, a predictor based on SVM. To our knowledge, it is the first web server
      for predicting PSBP. The SVM model was built with the feature of optimized
      dipeptide composition and 87.02% (MCC = 0.74; AUC = 0.91) of peptides were
      correctly classified by fivefold cross-validation. PSBinder can be used to
      exclude highly possible PSBP from biopanning results or to find novel candidates
      for polystyrene affinity tags. Either way, it is valuable for biotechnology
      community.

PMID- 29445739
TI  - Antifungal Compounds against Candida Infections from Traditional Chinese
      Medicine.
AB  - Infections caused by Candida albicans, often refractory and with high morbidity
      and mortality, cause a heavy burden on the public health while the current
      antifungal drugs are limited and are associated with toxicity and resistance.
      Many plant-derived molecules including compounds isolated from traditional
      Chinese medicine (TCM) are reported to have antifungal activity through different
      targets such as cell membrane, cell wall, mitochondria, and virulence factors.
      Here, we review the recent progress in the anti-Candida compounds from TCM, as
      well as their antifungal mechanisms. Considering the diverse targets and
      structures, compounds from TCM might be a potential library for antifungal drug
      development.

PMID- 29445742
TI  - Relationship between Undescended Testis Position and Prevalence of Testicular
      Appendices, Epididymal Anomalies, and Patency of Processus Vaginalis.
AB  - Objectives: To assess the incidence of testicular appendices (Tas), epididymal
      anomalies (EAs), and processus vaginalis (PV) patency in patients with
      undescended testis (UT) according to testicular position and to compare them with
      human fetuses. Methods: We studied 85 patients (108 testes) with cryptorchidism
      and compared the features with those of 15 fetuses (30 testes) with scrotal
      testes. We analyzed the relationships among the testis and epididymis, patency of
      PV, and the presence of TAs. We used the Chi-square test for statistical analysis
      (p < 0.05). Results: In 108 UT, 72 (66.66%) had PV patent, 67 (62.03%) had TAs,
      and 39 (36.12%) had EAs. Of the 108 UT, 14 were abdominal (12.96%; 14 had PV
      patency, 9 TAs, and 7 EAs); 81 were inguinal (75%; 52 had PV patency, 45 TAs, and
      31 EAs), and 13 were suprascrotal (12.03%; 6 had PV patency, 13 TAs, and 1 EAs).
      The patency of PV was more frequently associated with EAs (p = 0.00364). The EAs
      had a higher prevalence in UT compared with fetuses (p = 0.0005). Conclusions:
      Undescended testis has a higher risk of anatomical anomalies and the testes
      situated in abdomen and inguinal canal have a higher risk of presenting patency
      of PV and EAs.

PMID- 29445743
TI  - Assessment of Correlation between Intravoxel Incoherent Motion Diffusion Weighted
      MR Imaging and Dynamic Contrast-Enhanced MR Imaging of Sacroiliitis with
      Ankylosing Spondylitis.
AB  - The relationships between IVIM and DCE-MRI parameters in AS are not clear. We
      explore the correlation between intravoxel incoherent motion (IVIM) diffusion
      weighted imaging (DWI) and dynamic contrast-enhanced (DCE) parameters obtained on
      MR images in patients with ankylosing spondylitis (AS). Forty-four patients with
      AS were prospectively examined using a 1.5-T MR system. IVIM DWI was performed
      with 11 b values (range, 0-800 s/mm2) for all patients. The correlation
      coefficients between IVIM and DCE-MRI parameters were analyzed using Spearman's
      method. Our results showed that intra- and interobserver reproducibility were
      excellent to relatively good (ICC = 0.804-0.981; narrow width of 95% limits of
      agreement). Moderate positive correlations were observed between pure molecular
      diffusion (Ds) and maximum enhancement (ME) and relative enhancement (RE) (r  = 
      0.700, P < 0.001; r = 0.607, P < 0.001, resp.). Perfusion-related diffusion (Df)
      showed negative moderate correlation with ME (r  =  -0.608, P < 0.001). However,
      no correlation was observed between perfusion fraction (f) and any parameters of
      ME, RE, TTP, and BE (r = -0.093-0.213; P > 0.165). In conclusion, the IVIM
      parameters, especially f, might play a critical role in detecting the progression
      of AS, because it can provide more perfusion information compared with DCE-MRI;
      besides the IVIM MRI is a noninvasive method.

PMID- 29445744
TI  - Simvastatin Ameliorates PAK4 Inhibitor-Induced Gut and Lung Injury.
AB  - P21 activated kinase 4 (PAK4), a key regulator of cytoskeletal rearrangement and
      endothelial microparticles (EMPs), is released after lipopolysaccharide (LPS)
      stimulation. In addition, it participates in LPS-induced lung injury. In this
      study, forty-eight Sprague Dawley (SD) rats were divided into two groups,
      including PAK4 inhibitor (P) and PAK4 inhibitor + simvastatin (P + S) treatment
      groups. All rats were given PAK4 inhibitor (15 mg/kg/d) orally. Immediately after
      PAK4 inhibitor administration, simvastatin was injected intraperitoneally to P +
      S group animals at 20 mg/kg/day. Then, treatment effects on the intestinal
      mucosal barrier and lung injury caused by PAK4 inhibitor and simvastatin were
      assessed. The results showed that gut Zonula Occludens- (ZO-) 1, PAK4, mitogen
      activated protein kinase 4 (MPAK4), and CD11c protein levels were reduced, while
      plasma endotoxin levels were increased after administration of PAK4 inhibitor.
      Furthermore, compared with normal rats, wet-to-dry (W/D) values of lung tissues
      and circulating EMP levels were increased in the treatment group, while PAK4 and
      CD11c protein amounts were reduced. Therefore, in this lung injury process
      induced by PAK4 inhibitor, the protective effects of simvastatin were reflected
      by intestinal mucosal barrier protection, inflammatory response regulation via
      CD11c+ cells, and cytoskeleton stabilization. In summary, PAK4 is a key regulator
      in the pathophysiological process of acute lung injury (ALI) and can be a useful
      target for ALI treatment.

PMID- 29445745
TI  - Comment on "Responders to Platelet-Rich Plasma in Osteoarthritis: A Technical
      Analysis".

PMID- 29445746
TI  - Bone Response to Two Dental Implants with Different Sandblasted/Acid-Etched
      Implant Surfaces: A Histological and Histomorphometrical Study in Rabbits.
AB  - Background: Scientific evidence in the field of implant dentistry of the past 20
      years established that titanium rough surfaces have shown improved
      osseointegration rates. In a majority of dental implants, the surface
      microroughness was obtained by grit blasting and/or acid etching. The aim of the
      study was to evaluate in vivo two different highly hydrophilic surfaces at
      different experimental times. Methods: Calcium-modified (CA) and SLActive
      surfaces were evaluated and a total of 18 implants for each type of surface were
      positioned into the rabbit articular femoral knee-joint in a split model
      experiment, and they were evaluated histologically and histomorphometrically at
      15, 30, and 60 days of healing. Results: Bone-implant contact (BIC) at the two
      implant surfaces was significantly different in favor of the CA surface at 15
      days (p = 0.027), while SLActive displayed not significantly higher values at 30
      (p = 0.51) and 60 days (p = 0.061). Conclusion: Both implant surfaces show an
      intimate interaction with newly formed bone.

PMID- 29445747
TI  - Rhizospheric Bacillus subtilis Exhibits Biocontrol Effect against Rhizoctonia
      solani in Pepper (Capsicum annuum).
AB  - This study aimed at evaluating the ability of SL-44 to control Rhizoctonia solani
      and promote pepper (Capsicum annuum) growth. Strain SL-44 was isolated from plant
      rhizosphere and the pot experiment results indicated that the dry and fresh
      weights of pepper in SL-44 and Rhizoctonia solani (S-R) treatment were 45.5% and
      54.2% higher than those in Rhizoctonia solani (R) treatment and 18.2% and 31.8%
      higher than those in CK (control, noninoculation) treatment. The plant height in
      S-R treatment increased by 14.2% and 9.0% compared with those in the R and CK
      treatments, respectively. In vitro antagonism assay showed that SL-44 exhibited
      strong antifungal activity against the mycelial growth of Rhizoctonia solani,
      with an inhibition rate of 42.3%. The amount of phosphorus dissolved by SL-44
      reached 60.58 mg.L-1 in broth and 7.5 MUg.mL-1 IAA were secreted by SL-44. Strain
      SL-44 inhibited the growth of R. solani and improved biomass of pepper plants.
      Mass exchange and information transmission between the pepper plants and SL-44
      mutually promoted their development. Bacillus subtilis SL-44 has a great
      potential as biocontrol agent against Rhizoctonia solani on pepper plants.

PMID- 29445748
TI  - Oxidation Resistance of the Sulfur Amino Acids: Methionine and Cysteine.
AB  - Sulfur amino acids are a kind of amino acids which contain sulfhydryl, and they
      play a crucial role in protein structure, metabolism, immunity, and oxidation.
      Our review demonstrates the oxidation resistance effect of methionine and
      cysteine, two of the most representative sulfur amino acids, and their
      metabolites. Methionine and cysteine are extremely sensitive to almost all forms
      of reactive oxygen species, which makes them antioxidative. Moreover, methionine
      and cysteine are precursors of S-adenosylmethionine, hydrogen sulfide, taurine,
      and glutathione. These products are reported to alleviate oxidant stress induced
      by various oxidants and protect the tissue from the damage. However, the
      deficiency and excess of methionine and cysteine in diet affect the normal growth
      of animals; thereby a new study about defining adequate levels of methionine and
      cysteine intake is important.

PMID- 29445749
TI  - Impact of Chestnut and Quebracho Tannins on Rumen Microbiota of Bovines.
AB  - The use of phytogenic dietary additives is being evaluated as a means to improve
      animal productivity. The effect of tannins seems to be the influence not only
      directly on the digestive process through binding of dietary proteins but also
      indirectly over their effects on gastrointestinal microbiota. High-throughput
      sequencing of 16S rRNA gene was used to analyze the impact of dietary
      supplementation with a blend of chestnut and quebracho tannins on the rumen
      microbiota of Holstein steers. Bacterial richness was lower in tannins treated
      animals, while the overall population structure of rumen microbiota was not
      significantly disturbed by tannins. The ratio of the phyla Firmicutes and
      Bacteroidetes, a parameter associated with energy harvesting function, was
      increased in tannins supplemented animals, essentially due to the selective
      growth of Ruminococcaceae over members of genus Prevotella. Fibrolytic,
      amylolytic, and ureolytic bacterial communities in the rumen were altered by
      tannins, while methanogenic archaea were reduced. Furthermore, ruminal pH was
      significantly higher in animals supplemented with tannins than in the control
      group, while urease activity exhibited the opposite pattern. Further work is
      necessary to assess the relation between tannins impact on rumen microbiota and
      alteration of rumen fermentation parameters associated with bovine performance.

PMID- 29445750
TI  - The Association between Monocyte Surface CD163 and Insulin Resistance in Patients
      with Type 2 Diabetes.
AB  - Aim: To investigate the association between monocyte CD163 and insulin resistance
      in patients with type 2 diabetes. Methods: One hundred sixty-six patients with
      type 2 diabetes without inflammatory or chronic kidney disease were recruited.
      The monocyte CD163 levels were measured by flow cytometry and soluble CD163
      (sCD163) by ELISA. Insulin resistance was evaluated by the index of the
      homeostasis model assessment (HOMA-R). Results: The median sCD163 and monocyte
      CD163 expression levels were 582.9 (472.4-720.0) ng/ml and 6061 (4486-7876) mean
      fluorescent intensity (MFI), respectively. In a simple regression analysis,
      monocyte CD163 was inversely correlated with log [HOMA-R] (r = -0.257, p =
      0.010), and sCD163 was positively correlated with log [HOMA-R] (r = 0.198, p =
      0.042). In multiple regression analyses, monocyte CD163 was an independent
      contributor to log [HOMA-R] (beta = -0.220, p = 0.020) even after adjustment of
      various clinical factors for HOMA-R (R2 = 0.281, p = 0.001), whereas sCD163 was
      not. Conclusions: Monocyte surface CD163 expression levels were more
      significantly associated with insulin resistance than sCD163 in patients with
      type 2 diabetes, suggesting a novel pathophysiological role of CD163.

PMID- 29445751
TI  - Circulating Nesfatin-1 Levels and Type 2 Diabetes: A Systematic Review and Meta
      Analysis.
AB  - The role of nesfatin-1 in glucose homeostasis has been investigated previously.
      However, although numerous studies have examined the relationships between
      circulating nesfatin-1 levels and type 2 diabetes, the conclusions are
      contradictory. We aimed to probe the relationship between circulating nesfatin-1
      levels and type 2 diabetes by meta-analysis. Seven studies including 328 type 2
      diabetes patients and 294 control subjects were included. Although there was no
      obvious difference in circulating nesfatin-1 levels between patients with type 2
      diabetes and the control group (MD = -0.04; 95% CI = -0.32 to -0.23), subgroup
      analysis showed higher nesfatin-1 levels in newly diagnosed type 2 diabetes
      patients (MD = 0.59; 95% CI = 0.45 to 0.74) and significantly lower nesfatin-1
      levels in type 2 diabetes patients receiving antidiabetic treatment (MD = -0.26;
      95% CI = -0.33 to -0.20). In conclusion, the analysis supports a relationship
      between circulating nesfatin-1 levels and type 2 diabetes, where newly diagnosed
      type 2 diabetes was associated with an elevated Nesfatin-1 level, and type 2
      diabetes patients receiving antidiabetic treatment showed lower circulating
      nesfatin-1 levels.

PMID- 29445752
TI  - Improvement in Neuropathy Specific Quality of Life in Patients with Diabetes
      after Vitamin D Supplementation.
AB  - Objective: To assess the effect of vitamin D supplementation on neuropathy
      specific quality of life (NeuroQoL) in patients with painful diabetic neuropathy.
      Methods: This prospective, open label study was conducted between June 2012 and
      April 2013. Patients with symptomatic diabetic neuropathy were given a single
      dose of 600,000 IU intramuscular vitamin D, and NeuroQol was assessed at baseline
      and at five follow-up visits every 4 weeks. Results: Of 143 participants, 41.3%
      were vitamin D deficient (vitamin D < 20 ng/ml). Treatment with vitamin D
      resulted in a significant increase in 25(OH)D (P < 0.0001) and a significant
      improvement in the NeuroQoL subscale score for emotional distress (P = 0.04),
      with no significant change in the other NeuroQoL domains of painful symptoms and
      paresthesia, loss of temperature and touch sensation, unsteadiness, limitation in
      daily activities, and interpersonal problems. There was a significant reduction
      in patient perception about foot problems on QoL of "quite a lot" (P < 0.05) and
      "very much" (P < 0.0001) with a significant reduction in the baseline response of
      having a "poor" QoL from 5.2% to 0.7% (P < 0.0001) and an increase in the
      response of an "excellent QoL" from 1.5% to 7.4% (P < 0.0001). Conclusion:
      Vitamin D is effective in improving quality of life in patients with painful
      diabetic neuropathy.

PMID- 29445753
TI  - Treatments for Severe Cutaneous Adverse Reactions.
AB  - Severe cutaneous adverse reaction (SCAR) is life-threatening. It consists of
      Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with
      eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous
      pustulosis (AGEP), and generalized bullous fixed drug eruptions (GBFDE). In the
      past years, emerging studies have provided better understandings regarding the
      pathogenesis of these diseases. These diseases have unique presentations and
      distinct pathomechanisms. Therefore, theoretically, the options of treatments
      might be different among various SCARs. However, due to the rarity of these
      diseases, sufficient evidence is still lacking to support the best choice of
      treatment for patients with SCAR. Herein, we will provide a concise review with
      an emphasis on the characteristics and treatments of each SCAR. It may serve as a
      guidance based on the current best of knowledge and may shed light on the
      directions for further investigations.

PMID- 29445755
TI  - Immunomodulatory Effect of Flavonoids of Blueberry (Vaccinium corymbosum L.)
      Leaves via the NF-kappaB Signal Pathway in LPS-Stimulated RAW 264.7 Cells.
AB  - Objective: This study aimed to explore the immunoregulatory effect of flavonoids
      of blueberry (Vaccinium corymbosum L.) leaves (FBL). Methods: The flavonoids of
      blueberry leaves were prepared with 70% ethanol and were identified by
      ultraperformance liquid chromatography/quadrupole-time-of-flight mass
      spectrometry (UPLC/Q-Tof-MS). The immunoregulatory effect and possible regulatory
      mechanisms of FBL were investigated in lipopolysaccharide- (LPS-) induced RAW
      264.7 cells. Results: According to the results of UPLC/Q-Tof-MS, nine flavonoids
      of blueberry leaves were identified. FBL showed a significant reduction in the
      production of TNF-alpha in LPS-stimulated RAW 264.7 cells. FBL significantly
      decreased the expression of NF-kappaB p65 and P-NF-kappaB p65 in LPS-induced RAW
      264.7 cells in a dose-dependent manner. Conclusion: Our study showed the
      immunoregulatory effect of FBL through the suppression of TNF-alpha via the NF
      kappaB signal pathway.

PMID- 29445757
TI  - Alteration of Immune-Mechanisms by Human Microbiota and Development and
      Prevention of Human Diseases.

PMID- 29445754
TI  - Fundamentals and Methods for T- and B-Cell Epitope Prediction.
AB  - Adaptive immunity is mediated by T- and B-cells, which are immune cells capable
      of developing pathogen-specific memory that confers immunological protection.
      Memory and effector functions of B- and T-cells are predicated on the recognition
      through specialized receptors of specific targets (antigens) in pathogens. More
      specifically, B- and T-cells recognize portions within their cognate antigens
      known as epitopes. There is great interest in identifying epitopes in antigens
      for a number of practical reasons, including understanding disease etiology,
      immune monitoring, developing diagnosis assays, and designing epitope-based
      vaccines. Epitope identification is costly and time-consuming as it requires
      experimental screening of large arrays of potential epitope candidates.
      Fortunately, researchers have developed in silico prediction methods that
      dramatically reduce the burden associated with epitope mapping by decreasing the
      list of potential epitope candidates for experimental testing. Here, we analyze
      aspects of antigen recognition by T- and B-cells that are relevant for epitope
      prediction. Subsequently, we provide a systematic and inclusive review of the
      most relevant B- and T-cell epitope prediction methods and tools, paying
      particular attention to their foundations.

PMID- 29445756
TI  - Modulation of Tumor-Associated Macrophages (TAM) Phenotype by Platelet-Activating
      Factor (PAF) Receptor.
AB  - Platelet-activating factor (PAF) plays an important role in the pathogenesis of
      several types of tumors. The biological effects of PAF are mediated by the PAF
      receptor (PAFR), which can be expressed by tumor cells and host cells that
      infiltrate the tumor microenvironment. In the present study, we investigated the
      role of PAFR expressed by leukocytes that infiltrate two types of tumors, one
      that expresses PAFR (TC-1 carcinoma) and another that does not express the
      receptor (B16F10 melanoma) implanted in mice that express the receptor or not
      (PAFR KO). It was found that both tumors grew significantly less in PAFR KO than
      in wild-type (WT) mice. Analysis of the leukocyte infiltration shown in PAFR KO
      increased the frequency of neutrophils (Gr1+) and of CD8+ lymphocytes in B16F10
      tumors and of CD4+ lymphocytes in TC-1 tumors. PAFR KO also had a higher
      frequency of M1-like (CD11c+) and lower M2-like (CD206+) macrophages infiltrated
      in both tumors. This was confirmed in macrophages isolated from the tumors that
      showed higher iNOS, lower arginase activity, and lower IL10 expression in PAFR KO
      tumors than WT mice. These data suggest that in the tumor microenvironment,
      endogenous PAF-like activity molecules bind PAFR in macrophages which acquire an
      M2-like profile and this promotes tumor growth.

PMID- 29445758
TI  - Macrophage Polarization in Cerebral Aneurysm: Perspectives and Potential Targets.
AB  - Cerebral aneurysms (CAs) have become a health burden not only because their
      rupture is life threatening, but for a series of devastating complications left
      in survivors. It is well accepted that sustained chronic inflammation plays a
      crucial role in the pathology of cerebral aneurysms. In particular, macrophages
      have been identified as critical effector cells orchestrating inflammation in
      CAs. In recent years, dysregulated M1/M2 polarization has been proposed to
      participate in the progression of CAs. Although the pathological mechanisms of
      M1/M2 imbalance in CAs remain largely unknown, recent advances have been made in
      the understanding of the molecular basis and other immune cells involving in this
      sophisticated network. We provide a concise overview of the mechanisms associated
      with macrophage plasticity and the emerging molecular targets.

PMID- 29445759
TI  - Impact of the Polymorphism rs9264942 near the HLA-C Gene on HIV-1 DNA Reservoirs
      in Asymptomatic Chronically Infected Patients Initiating Antiviral Therapy.
AB  - Several genome-wide association studies have identified a polymorphism located 35
      kb upstream of the coding region of HLA-C gene (rs9264942; termed -35 C/T) as a
      host factor significantly associated with the control of HIV-1 viremia in
      untreated patients. The potential association of this host genetic polymorphism
      with the viral reservoirs has never been investigated, nor the association with
      the viral control in response to the treatment. In this study, we assess the
      influence of the polymorphism -35 C/T on the outcome of virus burden in 183
      antiretroviral-naive HIV-1-infected individuals who initiated antiviral treatment
      (study STIR-2102), analyzing HIV-1 RNA viremia and HIV-1 DNA reservoirs. The
      rs9264942 genotyping was investigated retrospectively, and plasma levels of HIV-1
      RNA and peripheral blood mononuclear cell- (PBMC-) associated HIV-1 DNA were
      compared between carriers and noncarriers of the protective allele -35 C before
      antiretroviral therapy (ART), one month after ART and at the end of the study (36
      months). HIV-1 RNA and HIV-1 DNA levels were both variables significantly
      different between carriers and noncarriers of the allele -35 C before ART. HIV-1
      DNA levels remained also significantly different one month posttherapy. However,
      this protective effect of the -35 C allele was not maintained after long-term
      ART.

PMID- 29445760
TI  - Corneal functional optical zone under monocular and binocular assessment.
AB  - Background: In this retrospective randomized case series, we compared bilateral
      symmetry between OD and OS eyes, intercorneal differences and Functional Optical
      Zone (FOZ) of the corneal aberrations. Methods: Sixty-seven normal subjects (with
      no ocular pathology) who never had any ocular surgery were bilaterally evaluated
      at Augenzentrum Recklinghausen (Germany). In all cases, standard examinations and
      corneal wavefront topography (OPTIKON Scout) were performed. The OD/OS bilateral
      symmetry was evaluated for corneal wavefront aberrations, and FOZ-values were
      evaluated from the Root-Mean-Square (RMS) of High-Order Wavefront-Aberration
      (HOWAb). Moreover, correlations of FOZ, spherical equivalent (SE), astigmatism
      power, and cardinal and oblique astigmatism for binocular vs. monocular, and
      binocular vs. intercorneal differences were analyzed. Results: Mean FOZ was 6.56
      +/- 1.13 mm monocularly, 6.97 +/- 1.34 mm binocularly, and 7.64 +/- 1.30 mm
      intercorneal difference, with all strongly positively correlated, showing that
      the diameter of glare-free vision is larger in binocular than monocular
      conditions. Mean SE was 0.78 +/- 1.30 D, and the mean astigmatism power
      (magnitude) was 0.46 +/- 0.52 D binocularly. The corresponding monocular values
      for these metrics were 0.78 +/- 1.30 D and 0.53 +/- 0.53 D respectively. SE,
      astigmatism magnitude, cardinal astigmatism component, and FOZ showed a strong
      correlation and even symmetry; and oblique astigmatism component showed odd
      symmetry indicating Enantiomorphism between the left and right eye. Conclusions:
      These results confirm OD-vs.-OS bilateral symmetry (which influences binocular
      summation) of HOWAb, FOZ, defocus, astigmatism power, and cardinal and oblique
      astigmatism. Binocular Functional Optical Zone calculated from corneal wavefront
      aberrations can be used to optimize refractive surgery design.

PMID- 29445761
TI  - Oxidative Stress Assays (arsenite and tBHP) in Caenorhabditis elegans.
AB  - Cells and organisms face constant exposure to reactive oxygen species (ROS),
      either from the environment or as a by-product from internal metabolic processes.
      To prevent cellular damage from ROS, cells have evolved detoxification
      mechanisms. The activation of these detoxification mechanisms and their
      downstream responses represent an overlapping defense response that can be
      tailored to different sources of ROS to adequately adapt and protect cells. In
      this protocol, we describe how to measure the sensitivity to oxidative stress
      from two different sources, arsenite and tBHP, using the nematode C. elegans.

PMID- 29445762
TI  - Distribution and Seasonal Activity of Phlebotominae Sand Flies in Yazd and Its
      Outskirts, Center of Iran.
AB  - Background: Phlebotominae sand flies are the main vectors of leishmaniasis and
      some other diseases. Materials and Methods: Using sticky traps, sand flies were
      collected fortnightly from outdoors and indoors areas of selected sites. Results:
      A total of 2032 specimens (498 in the city and 1534 in the outskirts of Yazd)
      belonging to 11 species were collected. The activity of sand flies started in
      early-April and ended in mid-November. There were two peaks of activity in the
      end of April and mid-September. Phlebotomus sergenti and P. papatasi were the
      most abundant species in the city and outskirts of Yazd city, respectively. Other
      species were P. salehi, P. ansarii, P. kazerouni, P. caucasicus, P. andrejevi, P.
      alexandri, P. mongolensis, Sergentomyia sintoni, and S. palestinensis.
      Conclusion: In comparison to some other parts of Iran, the extended period
      between two peaks suggests that the larvae to adult development of sand fly were
      delayed by the higher temperature of the summer months in Yazd province.

PMID- 29445763
TI  - Corrigendum to "Topical Colchicine Gel versus Diclofenac Sodium Gel for the
      Treatment of Actinic Keratoses: A Randomized, Double-Blind Study".
AB  - [This corrects the article DOI: 10.1155/2016/5918393.].

PMID- 29445764
TI  - Quantified Coexpression Analysis of Central Amygdala Subpopulations.
AB  - Molecular identification and characterization of fear controlling circuitries is
      a promising path towards developing targeted treatments of fear-related
      disorders. Three-color in situ hybridization analysis was used to determine
      whether somatostatin (SOM, Sst), neurotensin (NTS, Nts), corticotropin-releasing
      factor (CRF, Crf), tachykinin 2 (TAC2, Tac2), protein kinase c-delta (PKC-delta,
      Prkcd), and dopamine receptor 2 (DRD2, Drd2) mRNA colocalize in male mouse
      amygdala neurons. Expression and colocalization was examined across capsular
      (CeC), lateral (CeL), and medial (CeM) compartments of the central amygdala. The
      greatest expression of Prkcd and Drd2 were found in CeC and CeL. Crf was
      expressed primarily in CeL, while Sst-, Nts-, and Tac2-expressing neurons were
      distributed between CeL and CeM. High levels of colocalization were identified
      between Sst, Nts, Crf, and Tac2 within the CeL, while little colocalization was
      detected between any mRNAs within the CeM. These findings provide a more detailed
      understanding of the molecular mechanisms that regulate the development and
      maintenance of fear and anxiety behaviors.

PMID- 29445765
TI  - In Vivo Observation of Structural Changes in Neocortical Catecholaminergic
      Projections in Response to Drugs of Abuse.
AB  - Catecholaminergic (dopamine and norepinephrine) projections to the cortex play an
      important role in cognitive functions and dysfunctions including learning,
      addiction, and mental disorders. While dynamics of glutamatergic synapses have
      been well studied in such contexts, little is known regarding catecholaminergic
      projections, owing to lack of robust methods. Here we report a system to monitor
      catecholaminergic projections in vivo over the timeframes that such events occur.
      Green fluorescent protein (GFP) expression driven by tyrosine hydroxylase
      promoter in a transgenic mouse line enabled us to perform two-photon imaging of
      cortical catecholaminergic projections through a cranial window. Repetitive
      imaging of the same axons over 24 h revealed the highly dynamic nature of
      catecholaminergic boutons. Surprisingly, administration of single high dose
      methamphetamine (MAP) induced a transient increase in bouton volumes. This new
      method opens avenues for longitudinal in vivo evaluation of structural changes at
      single release sites of catecholamines in association with physiology and
      pathology of cortical functions.

PMID- 29445766
TI  - Ventral and Dorsal Pathways Relate Differently to Visual Awareness of Body
      Postures under Continuous Flash Suppression.
AB  - Visual perception includes ventral and dorsal stream processes. However, it is
      still unclear whether the former is predominantly related to conscious and the
      latter to nonconscious visual perception as argued in the literature. In this
      study upright and inverted body postures were rendered either visible or
      invisible under continuous flash suppression (CFS), while brain activity of human
      participants was measured with functional MRI (fMRI). Activity in the ventral
      body-sensitive areas was higher during visible conditions. In comparison,
      activity in the posterior part of the bilateral intraparietal sulcus (IPS) showed
      a significant interaction of stimulus orientation and visibility. Our results
      provide evidence that dorsal stream areas are less associated with visual
      awareness.

PMID- 29445767
TI  - Serotonin Differentially Regulates L5 Pyramidal Cell Classes of the Medial
      Prefrontal Cortex in Rats and Mice.
AB  - The prefrontal cortex receives a dense serotonergic innervation that plays an
      important role in its regulation. However, how serotonin regulates different
      pyramidal and interneuron cell classes in this area is incompletely understood.
      Previous work in rats has shown that serotonin differentially regulates two
      classes of pyramidal cells in layer 5. It excites one class by activating 5-HT2A
      receptors, whereas it more subtly modulates the integrative properties of the
      other by co-activating 5-HT1A and 5-HT2A receptors. Here we have used
      electrophysiological recordings, combined with retrograde labeling and
      morphological reconstruction, to show that the first cell class corresponds to
      long range corticofugal neurons and the second corresponds to intratelencephalic
      neurons. These results suggest that, in rats, serotonin facilitates subcortical
      output while more subtly modulating cortico-cortical and cortico-striatal output.
      Interestingly, these results obtained in rats differ from those previously
      reported for mouse prefrontal cortex. Therefore we reinvestigated the effects of
      serotonin in mice and confirmed that serotonin predominantly activates inhibitory
      5-HT1A receptors on long-range corticofugal cells. Thus serotonin exerts opposite
      effects on these cells in rats and mice. Finally, we determined whether cortical
      serotonin responsiveness in mice is regulated during development. Serotonin
      elicited predominantly depolarizing inward current responses during the early
      postnatal period, whereas inhibitory 5-HT1A receptor-mediated responses did not
      become evident until the end of the second postnatal week. These results reveal
      commonalities as well as unexpected differences in the serotonergic regulation of
      long-range corticofugal and intratelencephalic neurons of layer 5 in rat and
      mouse.

PMID- 29445768
TI  - HsTRPA of the Red Imported Fire Ant, Solenopsis invicta, Functions as a
      Nocisensor and Uncovers the Evolutionary Plasticity of HsTRPA Channels.
AB  - Solenopsis invicta, the red imported fire ant, represents one of the most
      devastating invasive species. To understand their sensory physiology, we
      identified and characterized their Hymenoptera-specific (Hs) TRPA channel,
      SiHsTRPA. Consistent with the sensory functions of SiHsTRPA, it is activated by
      heat, an electrophile, and an insect repellent. Nevertheless, SiHsTRPA does not
      respond to most of the honey bee ortholog (AmHsTRPA)-activating compounds. The
      jewel wasp ortholog (NvHsTRPA) is activated by these compounds even though it
      outgroups both AmHsTRPA and SiHsTRPA. Characterization of AmHsTRPA/SiHsTRPA
      chimeric channels revealed that the amino acids in the N terminus, as well as
      ankyrin repeat 2 (AR2) of AmHsTRPA, are essential for the response to camphor.
      Furthermore, amino acids in ARs 3 and 5-7 were specifically required for the
      response to diallyl disulfide. Thus, amino acid substitutions in the
      corresponding domains of SiHsTRPA during evolution would be responsible for the
      loss of chemical sensitivity. SiHsTRPA-activating compounds repel red imported
      fire ants, suggesting that SiHsTRPA functions as a sensor for noxious compounds.
      SiHsTRPA represents an example of the species-specific modulation of orthologous
      TRPA channel properties by amino acid substitutions in multiple domains, and
      SiHsTRPA-activating compounds could be used to develop a method for controlling
      red imported fire ants.

PMID- 29445769
TI  - Prefrontal theta-Burst Stimulation Disrupts the Organizing Influence of Active
      Short-Term Retrieval on Episodic Memory.
AB  - Dorsolateral prefrontal cortex (DLPFC) is thought to organize items in working
      memory and this organizational role may also influence long-term memory. To
      causally test this hypothesized role of DLPFC in long-term memory formation, we
      used theta-burst noninvasive stimulation (TBS) to modulate DLPFC involvement in a
      memory task that assessed the influence of active short-term retrieval on later
      memory. Human subjects viewed three objects on a grid and then either actively
      retrieved or passively restudied one object's location after a brief delay. Long
      term memory for the other objects was assessed after a delay to evaluate the
      beneficial role of active short-term retrieval on subsequent memory for the
      entire set of object locations. We found that DLPFC TBS had no significant
      effects on short-term memory. In contrast, DLPFC TBS impaired long-term memory
      selectively in the active-retrieval condition but not in the passive-restudy
      condition. These findings are consistent with the hypothesized contribution of
      DLPFC to the organizational processes operative during active short-term
      retrieval that influence long-term memory, although other regions that were not
      stimulated could provide similar contributions. Notably, active-retrieval and
      passive-restudy conditions were intermixed, and therefore nonspecific influences
      of stimulation were well controlled. These results suggest that DLPFC is causally
      involved in organizing event information during active retrieval to support
      coherent long-term memory formation.

PMID- 29445770
TI  - Subthalamic Neural Activity Patterns Anticipate Economic Risk Decisions in
      Gambling.
AB  - Economic decision-making is disrupted in individuals with gambling disorder, an
      addictive behavior observed in Parkinson's disease (PD) patients receiving
      dopaminergic therapy. The subthalamic nucleus (STN) is involved in the inhibition
      of impulsive behaviors; however, its role in impulse control disorders and
      addiction is still unclear. Here, we recorded STN local field potentials (LFPs)
      in PD patients with and without gambling disorder during an economic decision
      making task. Reaction times analysis showed that for all patients, the decision
      whether to risk preceded task onset. We compared then for both groups the STN LFP
      preceding high- and low-risk economic decisions. We found that risk avoidance in
      gamblers correlated with larger STN LFP low-frequency (<12-Hz) fluctuations
      preceding task onset. In particular, the amplitude of low-frequency LFP
      fluctuations carried significant information about future decisions. Decisions of
      patients not affected by gambling disorder were instead not correlated with
      pretask STN LFP. Our results suggest that STN activity preceding task onset
      affects risk decisions by preemptively inhibiting attraction to high but unlikely
      rewards in favor of a long-term payoff.

PMID- 29445771
TI  - Biomimetic Rotated Lamellar Plywood Motifs by Additive Manufacturing of Metal
      Alloy Scaffolds for Bone Tissue Engineering.
AB  - Additive manufacturing presents opportunities to treat bone defects using
      biomimetic tissue scaffolds. Past investigations have explored modulating
      scaffold mechanical properties through varying materials and geometric motifs.
      Herein, we applied the rotated plywood structure of bone tissue to a 3D printed
      scaffold with the goal of improving mechanical performance compared to an
      orthogonal mesh design commonly used in tissue scaffold applications. The
      scaffolds were subjected to uniaxial compression followed by scanning electron
      microscopy and microcomputer tomography. The uniaxial compression test was
      characterized through elastic modulus (mean 1.32 GPa biomimetic, 0.196 GPa
      orthogonal, p < 0.001), ultimate compressive strength (mean 16.546 MPa
      biomimetic, 6.309 MPa orthogonal design, p < 0.001), and ultimate compressive
      strain values (4.867% biomimetic, 9.000% orthogonal, p < 0.005). Correlation of
      microfracture imaging to bulk scaffold mode of failure suggest that utilizing the
      biomimetic plywood design not only improved mechanical performance, but also
      reduced asymmetrtic buckling, plastic deformation, and fracture propagation
      similar to bone tissue.

PMID- 29445772
TI  - A Review of Evidence Based Treatments for Transgender Youth Diagnosed with Social
      Anxiety Disorder.
AB  - In addition to the high prevalence of gender dysphoria among transgender youth,
      this population is at greater risk of suffering from additional mental health
      disorders, including social anxiety disorder, compared to their cisgender peers.
      Cognitive behavioral therapy (CBT) has been established as an effective form of
      treatment for social anxiety disorder. It is recommended that therapists modify
      and adapt CBT when working with minority groups such as transgender youth to
      ensure that the treatment is efficacious and culturally sensitive. However,
      literature assessing the efficacy of CBT for transgender youth with mental health
      issues is scant. As a result, there is no empirical literature on effective
      treatment for transgender youth who meet criteria for social anxiety disorder
      alone or youth who meet criteria for social anxiety disorder and gender
      dysphoria. This literature review aims to identify current research related to
      prevalence of mental health disorders in transgender youth, the current
      literature on adaptations of cognitive behavioral techniques, and the need for
      treatment research on adaptation of CBT for transgender individuals, specifically
      those with social anxiety disorder and gender dysphoria.

PMID- 29445773
TI  - Leveraging tuberculosis case relative locations to enhance case detection and
      linkage to care in Swaziland.
AB  - Background: In Swaziland, as in many high HIV/TB burden settings, there is not
      information available regarding the household location of TB cases for
      identifying areas of increased TB incidence, limiting the development of targeted
      interventions. Data from "Butimba", a TB REACH active case finding project, was
      re-analyzed to provide insight into the location of TB cases surrounding Mbabane,
      Swaziland. Objective: The project aimed to identify geographical areas with high
      TB burdens to inform active case finding efforts. Methods: Butimba implemented
      household contact tracing; obtaining landmark based, informal directions, to
      index case homes, defined here as relative locations. The relative locations were
      matched to census enumeration areas (known location reference areas) using the
      Microsoft Excel Fuzzy Lookup function. Of 403 relative locations, an enumeration
      area reference was detected in 388 (96%). TB cases in each census enumeration
      area and the active case finders in each Tinkhundla, a local governmental region,
      were mapped using the geographic information system, QGIS 2.16. Results: Urban
      Tinkhundla predictably accounted for most cases; however, after adjusting for
      population, the highest density of cases was found in rural Tinkhundla. There was
      no correlation between the number of active case finders currently assigned to
      the 7 Tinkhundla surrounding Mbabane and the total number of TB cases (Spearman
      rho = -0.57, p = 0.17) or the population adjusted TB cases (Spearman rho = 0.14,
      p = 0.75) per Tinkhundla. Discussion: Reducing TB incidence in high-burden
      settings demands novel analytic approaches to study TB case locations. We
      demonstrated the feasibility of linking relative locations to more precise
      geographical areas, enabling data-driven guidance for National Tuberculosis
      Programs' resource allocation. In collaboration with the Swazi National
      Tuberculosis Control Program, this analysis highlighted opportunities to better
      align the active case finding national strategy with the TB disease burden.

PMID- 29445774
TI  - An evaluation of immunization services, using the reaching every district
      criteria, in two districts of Gujarat, India.
AB  - Background: Immunizations are considered the most successful and cost-effective
      public health interventions employed today. While immunization coverage in India
      has improved dramatically in the last decade, areas of very low coverage persist.
      The University of Michigan School of Public Health and the Indian Institute of
      Public Health Gandhinagar collaborated to document strengths and weaknesses of
      immunization service delivery in two districts in India. Methods: This report
      describes a qualitative assessment of clinic level immunization service delivery
      in ten primary health centers (PHCs) located in two districts of Gujarat, India.
      Assessment criteria were derived from the Reaching Every District (RED) strategy
      that is intended to provide a framework for delivering childhood immunizations.
      Staff from the PHCs were interviewed in April 2013. Results: Interviews revealed
      several barriers to immunization service delivery including: 1) Vaccine and
      supply stockouts; 2) Hard to reach communities; 3) Unreliable Internet access; 4)
      Cold chain equipment malfunctions; 5) Inconsistently maintained and utilized
      immunization records and registries. Conclusions: Immunization service delivery
      is a complex process that can encounter barriers at many stages. A RED-based
      evaluation of the vaccine delivery system in Gujarat, India identified several
      points where the system was performing sub-optimally and possible solutions to
      successfully address these challenges.

PMID- 29445775
TI  - Torsion bottle, a very simple, reliable, and cheap tool for a basic scoliosis
      screening.
AB  - Background: One of the reasons that make scoliosis a disease that scares so much
      the parents is its specific characteristic of being difficult to detect on its
      onset.The aim of this paper is to check the possible usefulness of a simple tool
      (the torsion bottle) that has been developed with the aim to offer an instrument
      for home use by parents but also for screening purposes in the low-income
      countries. Methods: Study design: retrospective analysis to evaluate intra
      operator reliability of the tools and inter-operator repeatability using the
      torsion bottle.For the first and the second part of the study, 35 subjects were
      measured.The goal of the first experiment was to evaluate the reliability of the
      torsion bottle to identify all individuals who experienced a thoracic or lumbar
      prominence equal or greater than 7 degrees .The secondary aim was to verify the
      reliability of blinded inter-operator assessments, performed with the torsion
      bottle by two physiotherapists on the same patients. Results: The reliability of
      the assessments of the torsion bottle has been performed with the Kappa statistic
      to evaluate the measurement agreement.The results have shown that the intra
      operator reliability of the tool is very high between the measurements collected
      with the scoliometer(r) and those collected with the torsion bottle (kappa =
      0.9278; standard error = 0.7094).The data of the second part of the study show
      that the inter-operator reliability is good (kappa = 0.7988; standard error
      0.1368). Conclusion: The collected data showed that the torsion bottle revealed
      itself as an efficient tool to execute a basic screening to identify the presence
      of a prominence in a significant group of adolescents.

PMID- 29445776
TI  - Retinal nerve fiber layer sector-specific compromise in relapsing and remitting
      multiple sclerosis.
AB  - Objective: To evaluate quadrant and sector retinal nerve fiber layer (RNFL)
      thickness and total macular volume (TMV) in relapsing-remitting multiple
      sclerosis (RR-MS) patients. Methods: Optical coherence tomography measures of
      RNFL and TMV were studied in 321 eyes without prior optic neuritis (ON) (MS
      unaffected), 151 eyes with prior ON (MS affected), and 148 healthy control eyes.
      Results: Mean RNFL thickness was significantly lower in the MS affected and MS
      unaffected groups relative to the control group (p < 0.0001). RNFL thicknesses in
      the superior, inferior, and temporal quadrants were significantly reduced in MS
      unaffected (113 +/- 15 MUm, 119 +/- 17 MUm, 63 +/- 13 MUm) (p < 0.001) and MS
      affected groups (99 +/- 19 MUm, 103 +/- 21 MUm, 51 +/- 13 MUm) (p < 0.0001)
      compared with that in controls (120 +/- 14 MUm, 128 +/- 15 MUm, 69 +/- 8 MUm,
      respectively). TMV was significantly reduced in both the MS affected and MS
      unaffected groups compared with that in the controls (p < 0.0001). Conclusion:
      Quadrant, sector, and PMB RNFL thicknesses are significant individual measures in
      RR-MS for both affected and unaffected eyes and may prove valuable in future
      investigations including biomarker and outcomes research.

PMID- 29445777
TI  - (Z)-4-Chloro-N-{3-[(4-chlorophenyl)sulfonyl]-2,3-dihydrobenzo[d]thiazol-2
      ylidene}benzene-sulfonamide.
AB  - The title compound, C19H12Cl2N2O4S3, is related to a ditosylated 2
      iminobenzothiazole with the two methyl groups on the two phenyl rings replaced by
      chlorine. There is a weak intramolecular pi-pi contact between the two phenyl
      rings, with a centroid-to-centroid distance of 4.004 (2) A. The dihedral angle
      between the rings is 9.96 (13) degrees . An intramolecular C-H?O hydrogen bond
      stabilizes the molecular conformation.

PMID- 29445778
TI  - NADPH Oxidase-4 Driven Cardiac Macrophage Polarization Protects Against
      Myocardial Infarction-Induced Remodeling.
AB  - The reactive oxygen species-generating enzyme NADPH oxidase 4 (Nox4) is up
      regulated in the heart after myocardial infarction (MI). Mice with cardiomyocyte
      targeted Nox4 overexpression (TG) displayed increased macrophages in the heart at
      baseline, with skewing toward an M2 phenotype compared with wild-type controls
      (WT). After MI, TG mice had a higher proportion of M2 macrophages along with
      higher survival, decreased cardiac remodeling, and better contractile function
      than wild-type mice. The post-MI increase in cardiac matrix metalloproteinase-2
      activity was substantially blunted in TG mice. These results indicate that
      cardiomyocyte Nox4 modulates macrophage polarization toward an M2 phenotype,
      resulting in improved post-MI survival and remodeling, likely through the
      attenuation of cardiac matrix metalloproteinase-2 activity.

PMID- 29445779
TI  - Wireless Sensor-Dependent Ecological Momentary Assessment for Pediatric Asthma
      mHealth Applications.
AB  - Pediatric asthma is a prevalent chronic disease condition that can benefit from
      wireless health systems through constant symptom management. In this paper, we
      propose a smart watch based wireless health system that incorporates wireless
      sensing and ecological momentary assessment (EMA) to determine an individual's
      asthma symptoms. Since asthma is a multifaceted disease, this approach provides
      individualized symptom assessments through various physiological and
      environmental wireless sensor based EMA triggers specific to common asthma
      exacerbations. Furthermore, the approach described here improves compliance to
      use of the system through insightful EMA scheduling related to sensor detected
      environmental and physiological changes, as well as the patient's own schedule.
      After testing under several real world conditions, it was found that the system
      is sensitive to both physiological and environmental conditions that would cause
      asthma symptoms. Furthermore, the EMA questionnaires that were triggered based on
      these changes were specific to the asthma trigger itself, allowing for invaluable
      context behind the data to be collected.

PMID- 29445780
TI  - Actinide-based MOFs: a middle ground in solution and solid-state structural
      motifs.
AB  - In this review, we highlight how recent advances in the field of actinide
      structural chemistry of metal-organic frameworks (MOFs) could be utilized towards
      investigations relative to efficient nuclear waste administration, driven by the
      interest towards development of novel actinide-containing architectures as well
      as concerns regarding environmental pollution and nuclear waste storage. We
      attempt to perform a comprehensive analysis of more than 100 crystal structures
      of the existing An (U,Th)-based MOFs to establish a correlation between
      structural density and wt% of actinide and bridge structural motifs common for
      natural minerals with ones typically observed in the solution chemistry of
      actinides. In addition to structural considerations, we showcase the benefits of
      MOF modularity and porosity towards the stepwise building of hierarchical
      material complexity and the capture of nuclear fission products, such as
      technetium and iodine. We expect that these facets not only contribute to the
      fundamental science of actinide chemistry, but also could foreshadow pathways for
      more efficient nuclear waste management.

PMID- 29445781
TI  - Membrane bound COMT isoform is an interfacial enzyme: general mechanism and new
      drug design paradigm.
AB  - The enzyme catechol-O-methyltransferase (COMT) has water soluble (S-COMT) and
      membrane associated (MB-COMT), bitopic, isoforms. Of these MB-COMT is a drug
      target in relation to the treatment of Parkinson's disease. Using a combination
      of computational and experimental protocols, we have determined the substrate
      selection mechanism specific to MB-COMT. We show: (1) substrates with preferred
      affinity for MB-COMT over S-COMT orient in the membrane in a fashion conducive to
      catalysis from the membrane surface and (2) binding of COMT to its cofactor
      ADOMET induces conformational change that drives the catalytic surface of the
      protein to the membrane surface, where the substrates and Mg2+ ions, required for
      catalysis, are found. Bioinformatics analysis reveals evidence of this mechanism
      in other proteins, including several existing drug targets. The development of
      new COMT inhibitors with preferential affinity for MB-COMT over S-COMT is now
      possible and insight of broader relevance, into the function of bitopic enzymes,
      is provided.

PMID- 29445783
TI  - The construction of fluorescent heteropore covalent organic frameworks and their
      applications in spectroscopic and visual detection of trinitrophenol with high
      selectivity and sensitivity.
AB  - Two fluorescent covalent organic frameworks (COFs) which bear two kinds of pores
      with different sizes and shapes have been synthesized. The heteropore COFs
      exhibit spectroscopic and color changes to 2,4,6-trinitrophenol (TNP) with
      extremely high selectivity and sensitivity, which makes them excellent
      macroscopic chemosensors for the selective detection of TNP.

PMID- 29445785
TI  - A signal-on, colorimetric determination of deoxyribonuclease I activity utilizing
      the photoinduced synthesis of gold nanoparticles.
AB  - A simple, colorimetric method is developed for the determination of
      deoxyribonuclease I (DNase I) activity based on the novel finding that DNase I
      can promote the photoinduced synthesis of gold nanoparticles (AuNPs). In the
      absence of DNase I, a phosphorothioate (PS) DNA probe remains intact and captures
      Au(iii) through a strong Au-thiol interaction, which prevents the photoinduced
      synthesis of AuNPs, leaving the sample in a colorless state. On the other hand,
      in the presence of DNase I, the PS DNA probe is cleaved into small fragments that
      are removed via a simple purification process. The resulting solution, after the
      incubation with HAuCl4 and threonine (Thr), forms AuNPs by UV light irradiation
      with the aid of Thr which acts as a catalyst for the Au(iii) reduction process.
      As a result, a red-colored suspension is produced. By monitoring the color
      changes of the samples with the naked eye, the DNase I activity was conveniently
      determined. In addition, the clinical utility of this simple, yet highly
      efficient colorimetric strategy was verified by reliably quantifying the DNase I
      activities in a bovine urine sample. Importantly, the working principle designed
      for the determination of DNase I activity was successfully expanded for the
      detection of target nucleic acids, ensuring the universal applicability of the
      developed assay system.

PMID- 29445786
TI  - Amplified polarization properties of electrospun nanofibers containing
      fluorescent dyes and helical polymer.
AB  - Nanofibers with the cationic fluorescent molecules, 1-pyrenemethylamine
      hydrochloride (PyrMA) and alpha,beta,gamma,delta-tetrakis(1-methylpyridinium-4
      yl)porphyrin p-toluenesulfonate (TMPyP), in the presence of complementary anionic
      chiral polysaccharide, hyaluronic acid (HA) and transparent polymer, polyethylene
      oxide (PEO) were successfully prepared using an electrospinning technique. The
      results showed that the fluorescence spectra of electrospun nanofibers (ENFs) of
      PEO-HA-PyrMA exhibit a higher amount of pyrene excimer emission when the
      [PyrMA]/[HA] ratio was increased from 0.5 to 1, while the concentration of TMPyP
      had no remarkable effect on the fluorescence of the PEO-HA-TMPyP ENFs. From
      circular dichroism (CD) characterization, the ENFs of both dyes exhibit stronger
      intensities in the apparent CD spectra upon increasing the dye ratio. Moreover,
      they also showed higher CD intensities when compared with those of solutions and
      thin films prepared using other methods. The apparent CD in this work was proved
      to mainly originate from linear dichroism (LD) and linear birefringence (LB)
      obtained by macroscopic alignment along the electrospinning process. These
      results suggest the advantages of molecular orientation via electrospinning,
      together with chirality induction by incorporation of a chiral HA polymer. The
      enhancement of these polarization properties provides great possibilities for
      improving fluorescent-chiral nanofibers for further optoelectronic applications.

PMID- 29445787
TI  - Nanoparticles based on glycyrrhetinic acid modified porphyrin for photodynamic
      therapy of cancer.
AB  - Self-assembled small molecules, as a novel form of drug presentation, have
      splendid capabilities for water stability and cell endocytosis. Photodynamic
      therapy (PDT) is regarded as a promising cancer treatment because it is less
      invasive and has fewer side effects. In this work, an amphiphilic glycyrrhetinic
      acid-porphyrin conjugate (TPP-GA) was designed and synthesized, and this could
      self-assemble into nanoparticles (TPP-GA NPs) in water. The morphology of the TPP
      GA NPs was observed using transmission electron microscopy (TEM) and their
      stability in water was revealed by dynamic light scattering (DLS). The PDT effect
      of the TPP-GA NPs was confirmed by means of in vitro experiment, after
      photostability verification. It could be conceived that the application of TPP-GA
      NPs for PDT is a feasible choice and this work shows progress in the self
      assembly of amphiphilic small organic molecules.

PMID- 29445789
TI  - Hierarchical CoO/MnCo2O4.5 nanorod arrays on flexible carbon cloth as high
      performance anode materials for lithium-ion batteries.
AB  - A facile synthetic route is presented to fabricate highly ordered three
      dimensional hierarchical CoO/MnCo2O4.5 nanorod arrays on carbon cloth (CC) as a
      high performance anode material for lithium ion batteries (LIBs). Inheriting the
      merits from the CC substrate and the special hierarchical architecture, as well
      as the interfacial and synergistic effects between CoO nanorods and MnCo2O4.5
      nanosheets, the as-prepared product exhibits outstanding electrochemical
      performance in terms of high reversible capacity, cycling stability, and rate
      capability. Electrochemical characterization depicts that the hierarchical
      CoO/MnCo2O4.5 nanorod electrode can retain a high reversible capacity of about
      1183 mA h g-1 at 200 mA-1 for the second cycle and a high rate capacity of 657 mA
      h g-1 at 1000 mA-1. After 120 cycles, a reversible capacity of 1030 mA h g-1 at
      200 mA-1 can be maintained without obvious decay. These results demonstrate that
      the hierarchical CoO/MnCo2O4.5 nanorod array on CC is a promising candidate as an
      anode material for LIBs with superior properties.

PMID- 29445790
TI  - Green polymerizable deep eutectic solvent (PDES) type conductive paper for
      origami 3D circuits.
AB  - We report a green fabrication of conductive paper based on in situ polymerization
      of polymerizable deep eutectic solvents (PDESs) through a screen printing
      process. By pre-designed circuit paths and careful integration, on-demand
      input/output 3D circuits can be achieved, showing its flexibility to origami
      electronics.

PMID- 29445791
TI  - An Fe(TCNQ)2 nanowire array on Fe foil: an efficient non-noble-metal catalyst for
      the oxygen evolution reaction in alkaline media.
AB  - It is highly desirable to develop efficient and durable oxygen evolution reaction
      (OER) electrocatalysts. Herein, we report the in situ development of an Fe
      (tetracyanoquinodimethane)2 nanowire array on Fe foil (Fe(TCNQ)2/Fe) via a
      solution immersion method. As a non-noble-metal OER electrocatalyst, such
      Fe(TCNQ)2/Fe needs an overpotential of only 340 mV to drive a geometrical
      catalytic current density of 10 mA cm-2 in 1.0 M KOH. Notably, it also shows
      strong long-term electrochemical durability capable of maintaining its catalytic
      activity for at least 110 h.

PMID- 29445792
TI  - Understanding receptor-mediated endocytosis of elastic nanoparticles through
      coarse grained molecular dynamic simulation.
AB  - For nanoparticle (NP)-based drug delivery platforms, the elasticity of the NPs
      has a significant influence on their blood circulation time and cellular uptake
      efficiency. However, due to the complexity of the endocytosis process and the
      inconsistency in the definition of elasticity for NPs in experiments, the
      understanding about the receptor-mediated endocytosis process of elastic NPs is
      still limited. In this work, we developed a coarse-grained molecular dynamics
      (CGMD) model for elastic NPs. The energy change of the elastic NPs can be
      precisely controlled by the bond, area, volume and bending potentials of this
      CGMD model. To represent liposomes with different elasticities, we systematically
      varied the bending rigidity of elastic NPs in CGMD simulations. Additionally, we
      changed the radius of the elastic NPs to explore the potential size effect.
      Through virtual nano-indentation tests, we found that the effective stiffness of
      elastic NPs was determined by their bending rigidity and size. Afterwards, we
      investigated the receptor-mediated endocytosis process of elastic NPs with
      different sizes and bending rigidities. We found that the membrane wrapping of
      soft NPs was faster than that of the stiff ones at the early stage, due to the NP
      deformation induced large contact area between the NPs and the membrane. However,
      because of the large energy penalties induced by the NP deformation, the membrane
      wrapping speed of soft NPs slows down during the late stage. Eventually, the soft
      NPs are wrapped less efficiently than the stiff ones during the membrane wrapping
      process. Through systematic CGMD simulations, we found a scaling law between the
      cellular uptake efficiency and the phenomenal bending rigidity of elastic NPs,
      which agrees reasonably well with experimental observations. Furthermore, we
      observed that the membrane wrapping efficiencies of soft and stiff NPs with large
      sizes were close to each other, due to the stronger ligand-receptor binding force
      and smaller difference in the stiffness of elastic NPs. Our computational model
      provides an effective tool to investigate the receptor-mediated endocytosis of
      elastic NPs with well controlled mechanical properties. This study can also be
      applied to guide the design of NP-based drug carriers with high efficacy, by
      utilizing their elastic properties.

PMID- 29445793
TI  - A reaction of [2,6-(tBu2PO)2C6H3]NiSCH2Ph with BH3.THF: borane mediated C-S bond
      cleavage.
AB  - C-S bond activation of thiophenols and mercaptans is of great importance but has
      rarely been reported. In this paper we report the C-S bond cleavage of the
      thiolato ligand of [2,6-(tBu2PO)2C6H3]NiSCH2Ph (1) mediated by BH3.THF. The
      treatment of 1 with an excess amount of BH3.THF in THF at room temperature
      afforded the borohydride complex [2,6-(tBu2PO)2C6H3]Ni(eta2-BH4) (2) as the only
      product. The reaction of 1 with 2 equiv. of BH3.THF in THF at room temperature
      for 48 h produced the hydride complex [2,6-(tBu2PO)2C6H3]NiH (3) and the mercapto
      complex [2,6-(tBu2PO)2C6H3]NiSH (5). As a new complex, 5 was also independently
      synthesized by a salt metathesis reaction of the corresponding chloride complex
      with NaSH and fully characterized by multinuclear NMR, FTIR, HRMS, X-ray
      crystallography and elemental analysis. A possible mechanism for the formation of
      5 was proposed. It was supposed that 5 formed through BH3 mediated C-S bond
      cleavage of the thiolato ligand of 1. The result would initiate further studies
      on the transition metal catalyzed borane mediated C-S bond activation of
      mercaptans.

PMID- 29445794
TI  - High-pressure dissociation of selenium and tellurium.
AB  - Pressure-induced molecular dissociation provides significant insights into
      chemical bonding, governing the physical properties of molecular solids. Here the
      typical molecular solids, selenium and tellurium, have been explored
      experimentally to unearth the process of pressure-induced molecular dissociation.
      Before molecular dissociation, both commensurately and incommensurately modulated
      structures have been observed in these two elements. Upon compression, the
      successive commensurate-incommensurate phase transitions are proved by the soft
      amplitude (AMP) mode. The fitted critical pressure suggests that the molecular
      dissociation of Te is inferred to occur at 26.1 GPa in agreement with our XRD and
      Raman data. The current precise structural studies before pressure-induced
      molecular dissociation demonstrated in the elements selenium and tellurium will
      help in clarifying the mechanisms of molecular dissociation in related molecular
      solids.

PMID- 29445795
TI  - Zwitterionic peptide-capped gold nanoparticles for colorimetric detection of Ni2+
      .
AB  - Zwitterionic nanoparticles are typically utilized as nanoprobes and delivery
      vehicles in nanomedicine and therapeutics due to their resistance to
      interferences. Their high stability also shows great potential to be applied in
      sensing applications. Here, we report a selective, sensitive and rapid
      colorimetric sensing of nickel ions (Ni2+) using zwitterionic polypeptide,
      EKEKEKPPPPC (EK)3, capped gold nanoparticles (AuNP-(EK)3). By taking advantage of
      the alternate carboxylic (-COOH)/amine (-NH2) groups, the zwitterionic peptide
      can function dually by being able to sense metal ions and maintain colloidal
      stability. Ni2+ can trigger the aggregation of the AuNP-(EK)3 nanoprobe, which
      results in a red-to-purple color change of the AuNP-(EK)3 solution. Our 40 nm
      AuNP-(EK)3 nanoprobe can detect Ni2+ as low as 34 nM within 15 min with a linear
      range of 60-160 nM, and is stable in soil, urine and water samples. We
      demonstrate that the aggregation mechanism of the nanoprobe is due to the
      interactions between the -NH2 group of glutamic acid at the N-terminus of the
      peptide and Ni2+, and the aggregation process is reversible. Furthermore, the
      slight modification of two amino acid sequences at the N-terminus allows the
      nanoprobe to retain its stability, even in a high ionic strength medium. We
      believe that by adjusting or extending the peptide sequences, new metal ion
      selective peptides could be created.

PMID- 29445796
TI  - Synthesis and characterization of an iron complex bearing a hemilabile NNN-pincer
      for catalytic hydrosilylation of organic carbonyl compounds.
AB  - A low-coordinate iron(ii) complex (CztBu(PztBu)2)Fe[N(SiMe3)2], 1 bearing an NNN
      pincer ligand was prepared and fully characterized. Intramolecular C-H activation
      on the 5-position of a pyrazole at elevated temperatures was observed. Complex 1
      was found to be an efficient and chemoselective pre-catalyst for the
      hydrosilylation of organo carbonyl substrates.

PMID- 29445797
TI  - Spectroscopy as a tool to detect multinuclear Cu(ii)-triethanolamine complexes in
      aqueous solution.
AB  - Complexes of Cu(ii) with triethanolamine (TEA) are widely used in aqueous
      precursor solutions of Cu-based catalysts and metal oxides such as YBa2Cu3O7
      delta superconductors. An outstanding question is whether such complexes are
      multinuclear in solution. Here, we use various spectroscopic techniques to
      unmistakably prove the existence of such multimers. Firstly, we introduce an
      original approach based on NMR spectroscopy and the Evans method that establishes
      the existence of multimers in aqueous solution at pH 4 and higher, and allows
      precise monitoring of the formation of these complexes with increasing pH.
      Secondly, we use extended X-ray absorption fine structure (EXAFS) spectroscopy to
      show that a Cu-Cu interaction exists at pH 9.5, which is not observed in acidic
      (pH 2) solutions. Finally, NMRD measurements reveal additional structural
      information regarding the multinuclear complexes. Knowledge concerning the nature
      of Cu(ii)-TEA complexes in solution is of great relevance in view of the design
      of speciation models to predict the stability of copper triethanolamine-based
      precursor solutions.

PMID- 29445798
TI  - Solvation-controlled lithium-ion complexes in a nonflammable solvent containing
      ethylene carbonate: structural and electrochemical aspects.
AB  - The structural and electrochemical properties of lithium-ion solvation complexes
      in a nonflammable organic solvent, tris(2,2,2-trifluoroethyl)phosphate (TFEP)
      containing ethylene carbonate (EC), were investigated using vibrational
      spectroscopic and electrochemical measurements. Based on quantitative Raman and
      infrared (IR) spectral analysis of the Li bis(trifluoromethanesulfonyl)amide
      (TFSA) salt in TFEP + EC electrolytes, we successfully evaluated the individual
      solvation numbers of EC (nEC), TFEP (nTFEP), and TFSA- (nTFSA) in the first
      solvation sphere of the Li-ion. We found that the nEC value linearly increased
      with increasing EC mole fraction (xEC), whereas the nTFEP and nTFSA values
      gradually decreased with increasing nEC. The ionic conductivity and viscosity
      (Walden plots) indicated that mainly Li+TFSA- ion pairs formed in neat TFEP (xEC
      = 0). This ion pair gradually dissociated into positively charged Li-ion
      complexes as xEC increased, which was consistent with the Raman/IR spectroscopy
      results. The redox reaction corresponding to an insertion/desertion of Li-ion
      into/from the graphite electrode occurred in the LiTFSA/TFEP + EC system at xEC
      >= 0.25. The same was not observed in the lower xEC cases. We discussed the
      relation between Li-ion solvation and electrode reaction behaviors at the
      molecular level and proposed that nEC plays a crucial role in the electrode
      reaction, particularly in terms of solid electrolyte interphase formation on the
      graphite electrode.

PMID- 29445799
TI  - DNA nanodevices monitored with fluorogenic looped-out 2-aminopurine.
AB  - We report several DNA nanodevices monitored with fluorogenic looped-out 2
      aminopurine. It is found that looped-out 2-AP, an analogue of adenine, in split
      parallel G-quadruplexes, triplexes and duplexes always shows much higher
      fluorescence intensity than that in single- or double-stranded DNAs, due to the
      weaker quenching effects derived from the reduced base stacking environments.
      Taking advantage of these traits, we introduce a new strategy to monitor the
      behaviours of DNA nanodevices via the fluorescence signal output by utilizing
      changes in the base stacking environment of 2-AP. As proof-of-principle
      experiments, two nanoplatforms for detecting disease genes, as well as a triplex
      nanoswitch, are constructed and monitored by fluorogenic looped-out 2-AP,
      illustrating that fluorogenic looped-out 2-AP holds great promise for reading the
      behaviours of diverse DNA nanodevices. Compared with conventional fluorescence
      labelling, looped-out 2-AP as a reporter shows good photostability and can be
      quenched by base-pairing, thereby providing an efficient quencher-free
      methodology for monitoring DNA nanodevices.

PMID- 29445800
TI  - Acoustic separation in plastic microfluidics for rapid detection of bacteria in
      blood using engineered bacteriophage.
AB  - A more effective treatment of bacteremia requires a diagnostic platform that is
      both sensitive, accurate and rapid. Currently, clinical laboratory techniques
      require growth of bacteria prior to diagnosis, take days to complete, and leave
      empiric therapy and broad spectrum antibiotics as the only option at the onset of
      treatment. In order to bypass this growth requirement, we engineered a system
      that purifies bacteria from blood to improve performance in a bacteriophage-based
      luminescence assay. To perform the purification, we used acoustophoresis in
      plastic microfluidic chips, enabling future development into a low cost point-of
      care system. Acoustophoresis achieves differential separation on the basis of
      size differences between bacteria and blood cells. We show isolation of three
      known pathogen species, including members of both Gram-negative and positive
      bacteria from blood, and show isolation at clinically relevant concentrations.
      Using the device as a preparation step prior to the bacteriophage-based
      luminescence assay, we demonstrate a 33-fold improvement in limit of detection,
      compared with the unpurified sample, achieving a limit of detection of 6
      bacteria.

PMID- 29445801
TI  - Liquid crystal self-assembly of upconversion nanorods enriched by depletion
      forces for mesostructured material preparation.
AB  - Monodisperse rod-like colloidal particles are known for spontaneously forming
      both nematic and smectic liquid crystal phases, but their self-assembly was
      typically exploited from the fundamental soft condensed matter physics
      perspective. Here we demonstrate that depletion interactions, driven by non
      adsorbing polymers like dextran and surfactants, can be used to enrich the self
      organization of photon-upconversion nanorods into orientationally ordered nematic
      and smectic-like membrane colloidal superstructures. We study thermodynamic phase
      diagrams and demonstrate polarization-dependent photon upconversion exhibited by
      the ensuing composites, which arises from the superposition of unique properties
      of the solid nanostructures and the long-range ordering enabled by liquid
      crystalline self-organization. Finally, we discuss how our method of utilizing
      self-assembly due to the steric and electrostatic interactions, along with
      attractive depletion forces, can enable technological uses of lyotropic colloidal
      liquid crystals and mesostructured composite materials enabled by them, even when
      they are formed by anisotropic nanoparticles with relatively small aspect ratios.

PMID- 29445802
TI  - Pulsatile plasma filtration and cell-free DNA amplification using a water-head
      driven point-of-care testing chip.
AB  - We demonstrate a microfiltration chip that separates blood plasma by using water
      head-driven pulsatile pressures rather than any external equipment and use it for
      on-chip amplification of nucleic acids. The chip generates pulsatile pressures to
      significantly reduce filter clogging without hemolysis, and consists of an
      oscillator, a plasma-extraction pump, and filter units. The oscillator
      autonomously converts constant water-head pressure to pulsatile pressure, and the
      pump uses the pulsatile pressure to extract plasma through the filter. Because
      the pulsatile pressure can periodically clear blood cells from the filter
      surface, filter clogging can be effectively reduced. In this way, we achieve
      plasma extraction with 100% purity and 90% plasma recovery at 15% hematocrit.
      During a 10 min period, the volume of plasma extracted was 43 MUL out of a 243
      MUL extraction volume at 15% hematocrit. We also studied the influence of the
      pore size and diameter of the filter, blood loading volume, oscillation period,
      and hematocrit level on the filtration performance. To demonstrate the utility of
      our chip for point-of-care testing (POCT) applications, we successfully
      implemented on-chip amplification of a nucleic acid (miDNA21) in plasma filtered
      from blood. We expect our chip to be useful not only for POCT applications but
      also for other bench-top analysis tools using blood plasma.

PMID- 29445803
TI  - Poly(vinylidene fluoride)/poly(3-methylthiophene) core-shell nanocomposites with
      improved structural and electronic properties of the conducting polymer
      component.
AB  - We report significant improvements in the structure and electronic properties of
      a poly(3-alkylthiophene) representative, namely poly(3-methylthiophene) (P3MT),
      when it is synthesized in the presence of submicron electroactive poly(vinylidene
      fluoride) (PVDF) particles. The applied template oxidative synthesis leads to the
      formation of the PVDF/P3MT composite consisting of core-shell particles. The
      shells are constituted with a monolayer of 20-40 nm nanoparticles of the doped
      P3MT (P3MT-Cl) precipitated at the surface of the spherical PVDF cores. This
      morphology differs strongly from the hierarchical one of the neat P3MT
      synthesized without PVDF particles. In the latter case, 20-60 nm P3MT
      nanoparticles form ~200 nm aggregates, which, in turn, are arranged in a few
      micrometer agglomerates. Furthermore, we demonstrate that compared to the neat
      polymer, doped P3MT in the shells of the composite is characterized with higher
      effective conjugation length, regioregularity of the molecular structure,
      improved intrachain packing order and lower bipolaron/polaron ratio. These
      features of the PVDF/P3MT composite strongly suggest applicability of this
      material in various electronic devices. As a proof of concept, we report on an
      improved sensing performance of the PVDF/P3MT-Cl composite compared with the neat
      P3MT-Cl in detection of several volatile organic compounds known as markers for
      some diseases and toxic substances. We have discovered that the maximal
      improvement in the sensor response magnitude corresponds to the case when the
      values of the analyte electronegativity and polythiophene work function are
      close. We associate this behavior with a higher surface dipole component of the
      work function of the PVDF/P3MT-Cl composite compared to that of the neat
      conducting polymer.

PMID- 29445804
TI  - One-dimensional hydrogen bonding networks of bis-hydroxylated diamantane formed
      inside double-walled carbon nanotubes.
AB  - 1,6-Bis(hydroxymethyl)diamantane spontaneously aligns inside double-walled carbon
      nanotubes. The encapsulated molecules form a one-dimensional network within the
      double-walled carbon nanotubes through hydrogen bonding that leads to a highly
      dense filling as compared to unfunctionalized diamantane. Improving the
      encapsulation yields of precursors via functionalization is crucial to prepare
      novel one-dimensional materials.

PMID- 29445805
TI  - Transition of surface phase of cobalt oxide during CO oxidation.
AB  - In situ/operando studies of a heterogeneous catalyst are particularly valuable
      for achieving a fundamental understanding of catalytic mechanisms at a molecular
      level by establishing a correlation between the observed catalytic performance
      and the corresponding surface chemistry during catalysis. Herein, CO oxidation on
      cobalt oxides was studied via ambient pressure X-ray photoelectron spectroscopy
      (AP-XPS). During CO oxidation on CoO in the temperature range of 140-180  degrees
      C, the active surface phase of CoO progressively transforms to Co3O4. Kinetic
      studies of CO oxidation on the surface phase CoO at 80-120  degrees C and on the
      formed Co3O4 at 160-220  degrees C show that CoO and Co3O4 exhibit different
      activation barriers: 49.3 kJ mol-1 for CoO and 36.9 kJ mol-1 for Co3O4. This
      study demonstrates the transition of the active surface phase of a transition
      metal oxide-based catalyst under catalytic conditions with no change in the bulk
      phase of the catalyst.

PMID- 29445806
TI  - Intercalation of metformin into montmorillonite.
AB  - Metformin hydrochloride is an extensively used antidiabetic drug that according
      to the results reported here is able to spontaneously intercalate layered
      silicates like the montmorillonite clay mineral following an ion-exchange
      mechanism. The adsorption isotherm from water solutions shows a great affinity of
      metformin towards the clay mineral, which can retain about thrice the exchange
      capacity of the clay. The adsorbed excess was easily removed by washing with
      water, leading to an intercalation compound that contains 93 meq of metformin per
      100 g of montmorillonite, matching the CEC value of this clay. The intercalated
      metformin is arranged in the interlayer space as a monolayer of monoprotonated
      molecules, which remain strongly entrapped within the solid. These new hybrid
      materials were characterized by elemental chemical analysis, XRD, FTIR, TG-DTA,
      and NMR. We preliminary evaluated the use of the metformin-montmorillonite
      intercalation compound as a drug delivery system, determining the liberation
      kinetics of metformin at diverse pH values that mimic the gastrointestinal tract.
      Although the release rate was not totally slowed down, the system seems promising
      in view of further optimization for drug delivery applications.

PMID- 29445807
TI  - Base free N-alkylation of anilines with ArCH2OH and transfer hydrogenation of
      aldehydes/ketones catalyzed by the complexes of eta5-Cp*Ir(iii) with
      chalcogenated Schiff bases of anthracene-9-carbaldehyde.
AB  - The condensation of anthracene-9-carbaldehyde with 2
      (phenylthio/seleno)ethylamine results in Schiff bases [PhS(CH2)2C[double bond,
      length as m-dash]N-9-C14H9](L1) and [PhSe(CH2)2C[double bond, length as m-dash]N
      9-C14H9] (L2). On their reaction with [(eta5-Cp*)IrCl(MU-Cl)]2 and CH3COONa at 50
      degrees C followed by treatment with NH4PF6, iridacycles, [(eta5-Cp*)Ir(L
      H)][PF6] (1: L = L1; 2: L = L2), result. The same reaction in the absence of
      CH3COONa gives complexes [(eta5-Cp*)Ir(L)Cl][PF6] (3-4) in which L = L1(3)/L2(4)
      ligates in a bidentate mode. The ligands and complexes were authenticated with HR
      MS and NMR spectra [1H, 13C{1H} and 77Se{1H} (in the case of L2 and its complexes
      only)]. Single crystal structures of L2 and half sandwich complexes 1-4 were
      established with X-ray crystallography. Three coordination sites of Ir in each
      complex are covered with eta5-Cp* and on the remaining three, donor atoms present
      are: N, S/Se and C-/Cl-, resulting in a piano-stool structure. The moisture and
      air insensitive 1-4 act as efficient catalysts under mild conditions for base
      free N-alkylation of amines with benzyl alcohols and transfer hydrogenation (TH)
      of aldehydes/ketones. The optimum loading of 1-4 as a catalyst is 0.1-0.5 mol%
      for both the activations. The best reaction temperature is 80  degrees C for
      transfer hydrogenation and 100  degrees C for N-alkylation. The mercury poisoning
      test supports a homogeneous pathway for both the reactions catalyzed by 1-4. The
      two catalytic processes are most efficient with 3 followed by 4 > 1 > 2. The
      mechanism proposed on the basis of HR-MS of the reaction mixtures of the two
      catalytic processes taken after 1-2 h involves the formation of an alkoxy and
      hydrido species. The real catalytic species proposed in the case of iridacycles
      results due to the loss of the Cp* ring.

PMID- 29445808
TI  - Multi-spectrometer calibration transfer based on independent component analysis.
AB  - Calibration transfer is indispensable for practical applications of near infrared
      (NIR) spectroscopy due to the need for precise and consistent measurements across
      different spectrometers. In this work, a method for multi-spectrometer
      calibration transfer is described based on independent component analysis (ICA).
      A spectral matrix is first obtained by aligning the spectra measured on different
      spectrometers. Then, by using independent component analysis, the aligned
      spectral matrix is decomposed into the mixing matrix and the independent
      components of different spectrometers. These differing measurements between
      spectrometers can then be standardized by correcting the coefficients within the
      independent components. Two NIR datasets of corn and edible oil samples measured
      with three and four spectrometers, respectively, were used to test the
      reliability of this method. The results of both datasets reveal that spectra
      measurements across different spectrometers can be transferred simultaneously and
      that the partial least squares (PLS) models built with the measurements on one
      spectrometer can predict that the spectra can be transferred correctly on
      another.

PMID- 29445809
TI  - Lithium doping on 2D squaraine-bridged covalent organic polymers for enhancing
      adsorption properties: a theoretical study.
AB  - Lithium modification, especially quantitative and oriented doping, is an
      effective way to enhance the adsorption properties of covalent organic frameworks
      (e.g., CO2 and H2). Two-dimensional squaraine-bridged covalent organic polymers
      (SQ-COPs), with quantitative and oriented Li-doped open oxygen sites of the
      squaric-acid unit, are investigated for their CO2 capture properties by using
      first-principles calculation combined with grand canonical Monte Carlo (GCMC)
      simulation. It is found that owing to the strong affinity of Li atoms to the
      squaraine units of SQ-COPs, the gas adsorption capacity in SQ-COP-Li increased to
      3 times more than those of the pristine SQ-COPs. In particular, since the Li-O
      bonds between squaraine units and Li atoms can enhance the electrostatic
      interaction between the framework and CO2, the adsorption amount of CO2 in SQ-COP
      Li reaches an extremely high capacity of 83.4 and 202.0 mmol g-1 at 298 K and 100
      bar for 1-Li (SQ-COP-1-Li) and 3-Li (SQ-COP-3-Li), respectively. Such a high CO2
      uptake means that 3-Li outperforms the best 3D COF (COF-05) materials so far
      reported, and is even twice that of MOF-177 and IRMOF-10. Even at 30 bar and 298
      K, the CO2 uptake values of 49.2 mmol g-1 of 1-Li and 61.5 mmol g-1 of 3-Li are
      far higher than 29.7 mmol g-1 of Li-doped COF-102 and 42.0 mmol g-1 of Li-doped
      COF-105. Moreover, the selectivity of CO2/H2 and CO2/CH4 in 1-Li reaches 19 and
      5.4 at 273 K, and 10.3 and 3.6 at 298 K, respectively. Therefore, such Li-doped
      SQ-COPs might be an environmentally friendly candidate for high CO2 capture.
      Furthermore, the possible synthesis pathways of SQ-COP-Li are investigated, and
      it is indicated that the use of lithium di-isopropylamide and lithium naphthalene
      as dopants is energetically favorable. The findings in this work are expected to
      provide new ideas for metal doping and extended applications of functionalized
      materials.

PMID- 29445811
TI  - Metal-free synthesis of imidazole by BF3.Et2O promoted denitrogenative
      transannulation of N-sulfonyl-1,2,3-triazole.
AB  - BF3.Et2O promoted metal-free denitrogenative transannulation of N-sulfonyl-1,2,3
      triazole was reported. Rather than transition metals, BF3.Et2O was employed for
      the first time to promote the formation of alpha-diazoimines from N-sulfonyl
      1,2,3-triazoles in nitriles, leading to the synthesis of various imidazoles. The
      protocol tolerates a broad range of functional groups and could also be applied
      to the late-stage modification of bioactive molecules, demonstrating the
      potential of this protocol in organic synthesis. A plausible mechanism was
      proposed.

PMID- 29445812
TI  - 3D cellular structures and co-cultures formed through the contactless magnetic
      manipulation of cells on adherent surfaces.
AB  - A magnet array is employed to manipulate diamagnetic cells that are contained in
      paramagnetic medium to demonstrate for the first time the contactless bioprinting
      of three-dimensional (3D) cellular structures and co-cultures of breast cancer
      MCF-7 and endothelial HUVEC at prescribed locations on tissue culture treated
      well plates. Sequential seeding of different cell lines and the spatial
      displacement of the magnet array creates co-cultured cellular structures within a
      well without using physically intrusive well inserts. Both monotypic and co
      culture experiments produce morphologically rich 3D cell structures that are
      otherwise absent in regular monolayer cell cultures. The magnetic contactless
      bioprinting of cells provides further insight into cell behaviour, invasion
      strategies and transformations that are useful for potential applications in drug
      screening, 3D cell culture formation and tissue engineering.

PMID- 29445813
TI  - An insight into the origin of room-temperature ferromagnetism in SnO2 and Mn
      doped SnO2 quantum dots: an experimental and DFT approach.
AB  - SnO2 and Mn-doped SnO2 single-phase tetragonal crystal structure quantum dots
      (QDs) of uniform size with control over dopant composition and microstructure
      were synthesized using the high pressure microwave synthesis technique. On a
      broader vision, we systematically investigated the influence of dilute Mn ions in
      SnO2 under the strong quantum confinement regime through various experimental
      techniques and density functional theoretical (DFT) calculations to disclose the
      physical mechanism governing the observed ferromagnetism. DFT calculations
      revealed that the formation of the stable (001) surface was much more
      energetically favorable than that of the (100) surface, and the formation energy
      of the oxygen vacancies in the stable (001) surface was comparatively higher in
      the undoped SnO2 QDs. X-ray photoelectron spectroscopy (XPS) and first-principles
      modeling of doped QDs revealed that the lower doping concentration of Mn favored
      the formation of MnO-like (Mn2+) structures in defect-rich areas and the higher
      doping concentration of Mn led to the formation of multiple configurations of Mn
      (Mn2+ and Mn3+) in the stable surfaces of SnO2 QDs. Electronic absorption spectra
      indicated the characteristic spin allowed ligand field transitions of Mn2+ and
      Mn3+ and the red shift in the band gap. DFT calculations clearly indicated that
      only the substitutional dopant antiferromagnetic configurations were more
      energetically favorable. The gradual increase of magnetization at a low level of
      Mn-doping could be explained by the prevalence of antiferromagnetic manganese
      vacancy pairs. Higher concentrations of Mn led to the appearance of ferromagnetic
      interactions between manganese and oxygen vacancies. The increase in the
      concentration of metallic dopants caused not just an increase in the total
      magnetic moment of the system but also changed the magnetic interactions between
      the magnetic moments on the metal ions and oxygen. The present study provides new
      insight into the fundamental understanding of the origin of ferromagnetism in
      transition metal-doped QDs.

PMID- 29445814
TI  - Anisotropic flexible transparent films from remaining wood microstructures for
      screen protection and AgNW conductive substrate.
AB  - Flexible transparent conductive films or substrates prepared from plastics or
      cellulose are widely used in optoelectronic devices. However, all of these films
      or substrates are fabricated by complex and expensive methods, which consume much
      energy and time. In this work, we report for the first time a remarkably facile
      and effective approach for fabricating flexible transparent films directly from
      wood. The resulting films exhibit an array of exceptional optical and mechanical
      properties. The well-aligned cell structures in natural wood are maintained
      during delignification, leading to anisotropic films with high transparency (~90%
      transmittance). These anisotropic films with well-aligned cell structures show
      mechanical tensile strengths higher than those of the original wood, and can be
      used as screen protection films for cellphones. Furthermore, ultrathin, highly
      transparent, and outstandingly conductive films have been prepared from such
      films and silver nanowires (AgNWs) using the Meyer technique. A conductive film
      with an optimal area density (341 mg m-2) of AgNWs showed outstanding synergistic
      properties, with a transmittance of 80% and a sheet resistance of 11 Omega sq-1,
      equal to the conductivity of ITO. Of importance here is that the low-cost
      anisotropic transparent wood film shows promising potential for electronics
      applications in solar cells, flexible displays, and other products.

PMID- 29445815
TI  - Collisions of noble gas atoms with graphene and a graphene nanodome.
AB  - The collisions of noble gas atoms with graphene and a graphene nanodome were
      investigated by employing first principles molecular dynamics calculations. By
      analyzing the electron-related properties of the collision process, the atom
      dynamics and the deformation of the graphene/nanodome, our results show a
      difference between the elastic properties of the nanodome and graphene.
      Generally, the nanodome can more easily revert to its initial conformation. The
      final kinetic energy, Ef, of the atom that collides with the nanodome is larger
      than the Ef of the atom that collides with graphene. In addition, the
      relationship between the initial kinetic energy of the atom, Ek0, and its
      corresponding proportion of energy loss, chi, is linear (except for the Kr atom).
      Our research will probably contribute to the investigation of the 2D materials'
      mechanical properties and their surface morphology. Moreover, due to its novel
      mechanical properties, the graphene nanodome is an extraordinary nano
      architecture which can be employed to protect nano-devices from damage and
      injury.

PMID- 29445816
TI  - Organocatalytic asymmetric Michael/hemiacetalization/acyl transfer reaction of
      alpha-nitroketones with o-hydroxycinnamaldehydes: synthesis of 2,4-disubstituted
      chromans.
AB  - An organocatalytic asymmetric cascade Michael/hemiketalization/acyl transfer
      reaction between o-hydroxycinnamaldehydes and alpha-nitroketones is developed.
      Prolinol TMS ether catalyst in combination with benzoic acid was found to be the
      most effective for this reaction which proceeds through an equilibrium of lactols
      to provide a single diastereomer of enantiopure 2,4-disubstituted chromans.

PMID- 29445820
TI  - A drastic influence of the anion nature and concentration on high pressure
      intrusion-extrusion of electrolyte solutions in Silicalite-1.
AB  - High pressure intrusion-extrusion of concentrated solutions of sodium salts in a
      pure-silica MFI-type zeolite (Silicalite-1) was studied for potential
      applications in mechanical energy absorption and storage. It was discovered that
      the anion nature has a drastic influence on the behavior and the energetic
      performances of "Silicalite-1 - concentrated Na+X- solution" systems, where X =
      Cl-, Br-, I-, NO2-, NO3-, ClO4- and CrO42-. In the case of NaNO2, NaClO4,
      Na2CrO4, and NaI a combination of bumper and shock-absorber behaviors with a
      partial irreversible solution intrusion was observed, whereas a fully reversible
      spring behavior is demonstrated for the intrusion-extrusion of NaBr, NaCl and
      NaNO3 solutions. In comparison with water, the intrusion pressure increases for
      all the solutions except for NaClO4 one. The irreversibility of intrusion
      decreases with a dilution rate, and the behavior of the corresponding systems
      with diluted solutions becomes very close. The variation of the system behavior
      and intrusion pressure values can be related to a different affinity of the
      corresponding anions for the pores of Silicalite-1. The samples before and after
      intrusion-extrusion experiments were characterized using several structural and
      physicochemical methods (XRD, TGA, solid-state NMR, and N2 physisorption), but no
      significant structural difference was observed.

PMID- 29445823
TI  - Mixed-matrix materials using metal-organic polyhedra with enhanced compatibility
      for membrane gas separation.
AB  - Discrete metal-organic polyhedra (MOPs) containing copper(ii), palladium(ii), and
      iron(ii) nodes were synthesized as fillers for mixed-matrix materials (MMMs) with
      a polyvinylidine fluoride (PVDF) polymer phase and contrasted against an MMM
      containing a metal-organic framework, MOF-5. When a given MOP was soluble in the
      precursor solutions, the resulting MMMs were thin, flexible, and homogeneous
      based on microscopy and SEM imaging. Analogous MMM formation using either
      insoluble MOPs or the inherent insoluble MOF-5 showed a higher degree of phase
      separation and inhomogeneity. Even when a MOP was not fully soluble, a
      significant particle size decrease was observed in contrast to the MOF-5
      materials wherein the crystallites remained largely intact. This is a consequence
      of solubilizing the MOP fillers into the polymer solvent. The crystallinity and
      thermal stabilities of the MMMs were compared to pure PVDF using powder X-ray
      diffraction, and differential scanning calorimetry, indicating that the
      incorporation of MOPs both decreased overall crystallinity as well as increased
      thermal stability. In addition, MMMs containing PdMOP and FeMOP showed improved
      gas permeabilities relative to pure PVDF for H2, N2, CH4, and CO2, with the 10
      wt% FeMOP membrane more selective for CO2 over N2 and H2.

PMID- 29445821
TI  - Phase equilibrium and physical properties of biobased ionic liquid mixtures.
AB  - Protic ionic liquid crystals (PILCs) obtained from natural sources are promising
      compounds due to their peculiar properties and sustainable appeal. However,
      obtaining PILCs with higher thermal and mechanical stabilities for product and
      process design is in demand and studies on such approaches using this new IL
      generation are still scarce. In this context, this work discloses an alternative
      way for tuning the physicochemical properties of ILCs by mixing PILs. New binary
      mixtures of PILs derived from fatty acids and 2-hydroxy ethylamines have been
      synthesized here and investigated through the characterization of the solid-solid
      [liquid crystal]-liquid thermodynamic equilibrium and their rheological and
      critical micellar concentration profiles. The mixtures presented a marked
      nonideal melting profile with the formation of solid solutions. This work
      revealed an improvement of the PILCs' properties based on a significant increase
      in the ILC temperature domain and the obtainment of more stable mesophases at
      high temperatures when compared to pure PILs. In addition, mixtures of PILs also
      showed significant changes in their non-Newtonian and viscosity profile up to 100
      s-1, as well as mechanical stability over a wide temperature range. The
      enhancement of the physicochemical properties of PILs here disclosed by such an
      approach leads to more new possibilities of their industrial application at high
      temperatures.

PMID- 29445824
TI  - Understanding Bacterial Antibiotic Resistance and Pathogenicity Through
      Investigating Bacterial Membrane Proteins.

PMID- 29445825
TI  - Microglial IL-1beta progressively increases with duration of alcohol consumption.
AB  - Chronic alcohol abuse leads to severe brain damage. Although the underlying
      neuropathological processes are largely unknown, recent studies show that chronic
      alcohol consumption leads to neuroinflammation and may result in
      neurodegeneration and impaired neuronal connectivity. Long-term alcohol
      consumption promotes the production of pro-inflammatory cytokines, such as TNF
      alpha and IL-1beta, and activates microglia cells in the brain. As it has not yet
      been investigated to what extent these processes dependent on the duration of
      alcohol consumption or whether microglia are source of pro-inflammatory cytokines
      in vivo, this study investigated the expression of the pro-inflammatory cytokine,
      IL-1beta, in microglia at different time points in mice chronically exposed to
      alcohol. In the present study, we exposed mice to 2, 6, and 12 months of alcohol
      consumption, and using immunohistochemistry, analyzed the expression of the
      microglial marker, Iba1, together with the pro-inflammatory cytokine IL-1beta in
      several cortical regions. Moreover, we investigated the effect of pro
      inflammatory activation of microglia on neuronal density. We found that alcohol
      drinking progressively enhanced IL-1beta expression in microglia, which was
      paralleled with an overall increased microglial density after long-term alcohol
      consumption. However, we did not find changes in the neuronal density or cortical
      volume after long-term alcohol consumption. These data show that 12 months of
      alcohol drinking leads to a pro-inflammatory activation of microglia, which may
      contribute to impaired neuronal connectivity in the cortex. Anti-inflammatory
      drug treatment during or after chronic alcohol consumption may thus provide a
      strategy for restoring brain homeostasis.

PMID- 29445827
TI  - RE: "Predictors for uroseptic shock in patients who undergo minimally invasive
      percutaneous nephrolithotomy".

PMID- 29445826
TI  - Genome-Based Comparison of Clostridioides difficile: Average Amino Acid Identity
      Analysis of Core Genomes.
AB  - Infections due to Clostridioides difficile (previously known as Clostridium
      difficile) are a major problem in hospitals, where cases can be caused by
      community-acquired strains as well as by nosocomial spread. Whole genome
      sequences from clinical samples contain a lot of information but that needs to be
      analyzed and compared in such a way that the outcome is useful for clinicians or
      epidemiologists. Here, we compare 663 public available complete genome sequences
      of C. difficile using average amino acid identity (AAI) scores. This analysis
      revealed that most of these genomes (640, 96.5%) clearly belong to the same
      species, while the remaining 23 genomes produce four distinct clusters within the
      Clostridioides genus. The main C. difficile cluster can be further divided into
      sub-clusters, depending on the chosen cutoff. We demonstrate that MLST, either
      based on partial or full gene-length, results in biased estimates of genetic
      differences and does not capture the true degree of similarity or differences of
      complete genomes. Presence of genes coding for C. difficile toxins A and B
      (ToxA/B), as well as the binary C. difficile toxin (CDT), was deduced from their
      unique PfamA domain architectures. Out of the 663 C. difficile genomes, 535
      (80.7%) contained at least one copy of ToxA or ToxB, while these genes were
      missing from 128 genomes. Although some clusters were enriched for toxin
      presence, these genes are variably present in a given genetic background. The CDT
      genes were found in 191 genomes, which were restricted to a few clusters only,
      and only one cluster lacked the toxin A/B genes consistently. A total of 310
      genomes contained ToxA/B without CDT (47%). Further, published metagenomic data
      from stools were used to assess the presence of C. difficile sequences in blinded
      cases of C. difficile infection (CDI) and controls, to test if metagenomic
      analysis is sensitive enough to detect the pathogen, and to establish strain
      relationships between cases from the same hospital. We conclude that metagenomics
      can contribute to the identification of CDI and can assist in characterization of
      the most probable causative strain in CDI patients.

PMID- 29445828
TI  - The neural circuits of number and letter copying: an fNIRS study.
AB  - In our daily lives, we are constantly exposed to numbers and letters. However, it
      is still under debate how letters and numbers are processed in the brain, while
      information on this topic would allow for a more comprehensive understanding of,
      for example, known influences of language on numerical cognition or neural
      circuits shared by numerical cognition and language processing. Some findings
      provide evidence for a double dissociation between numbers and letters, with
      numbers being represented in the right and letters in the left hemisphere, while
      the opposing view suggests a shared neural network. Since processing may depend
      on the task, we address the reported inconsistencies in a very basic symbol
      copying task using functional near-infrared spectroscopy (fNIRS). fNIRS data
      revealed that both number and letter copying rely on the bilateral middle and
      left inferior frontal gyri. Only numbers elicited additional activation in the
      bilateral parietal cortex and in the left superior temporal gyrus. However, no
      cortical activation difference was observed between copying numbers and letters,
      and there was Bayesian evidence for common activation in the middle frontal gyri
      and superior parietal lobules. Therefore, we conclude that basic number and
      letter processing are based on a largely shared cortical network, at least in a
      simple task such as copying symbols. This suggests that copying can be used as a
      control condition for more complex tasks in neuroimaging studies without
      subtracting stimuli-specific activation.

PMID- 29445829
TI  - [Treatment of latent hypothyroidism in the elderly : Thyroid hormone replacement
      for untreated older adults with subclinical hypothyroidism (TRUST)].

PMID- 29445830
TI  - Bone health assessment in older people with or without muscle health impairment.
AB  - : This study investigated the relationship between muscle and bone status in
      elderly individuals. Our results suggested links between sarcopenia and
      osteoporosis; impairment in muscle status (i.e., muscle mass, muscle strength,
      and physical performance) is associated with deterioration in bone mass and
      texture subsequently leading to an increased risk of fracture. INTRODUCTION:
      Accumulating evidence has shown associations between sarcopenia and osteoporosis,
      but existing studies face inconsistencies in the clinical definition of both
      conditions. Thus, we sought to investigate bone health among older individuals
      with or without muscle health impairment. METHODS: We conducted an analysis of
      cross-sectional data available from the Sarcopenia and Physical Impairment with
      Advancing Age (SarcoPhAge) study. Sarcopenia was diagnosed according to the
      European Working Group on Sarcopenia in Older People (EWGSOP) (i.e., a low muscle
      mass plus either low muscle strength or low physical performance). Muscle mass
      and areal bone mineral density (aBMD) were determined using dual-energy X-ray
      absorptiometry (DEXA). Muscle strength was assessed using a hand dynamometer, and
      physical performance was assessed with the Short Physical Performance Battery
      test. Using the cutoff limits proposed by the EWGSOP, we have classified women in
      the "low SMI group" when its value was < 5.50 kg/m2, in the "low muscle strength
      group" when strength was < 20 kg, and in the "low physical performance group"
      when SPPB < 8 points. The thresholds of < 7.26 kg/m2 (for SMI), < 30 kg (for
      muscle strength), and SPPB < 8 points were used for men. The 10-year fracture
      risk was obtained using the FRAX(r) tool. Moreover, bone texture was determined
      using the trabecular bone score (TBS) method. RESULTS: The study sample consisted
      of 288 older subjects aged 74.7 +/- 5.7 years, and 59.0% of the subjects were
      women. Sarcopenia was diagnosed in 43 individuals (14.9%), and osteoporosis was
      diagnosed in 36 subjects (12.5%). Moreover, aBMD values were, most of the time,
      lower in older men and women with muscle impairment (i.e., low muscle mass, low
      muscle strength, and low physical performance). For these subjects, we also noted
      a higher probability of fracture. When comparing bone quality, there were no
      significant differences in the TBS values between sarcopenic and non-sarcopenic
      older men and women or between those with low and high muscle mass. However, when
      controlling for confounders (i.e., age, BMI, number of co-morbidities, smoking
      status, and nutritional status), TBS values were lower in older women with low
      muscle strength (p = 0.04) and in older men with low physical performance (p =
      0.01). CONCLUSIONS: Our study showed interrelationships between components of
      sarcopenia and osteoporosis, with older subjects with muscle impairment having
      poorer bone health.

PMID- 29445832
TI  - Analytical challenges in sports drug testing.
AB  - Analytical chemistry represents a central aspect of doping controls. Routine
      sports drug testing approaches are primarily designed to address the question
      whether a prohibited substance is present in a doping control sample and whether
      prohibited methods (for example, blood transfusion or sample manipulation) have
      been conducted by an athlete. As some athletes have availed themselves of the
      substantial breadth of research and development in the pharmaceutical arena,
      proactive and preventive measures are required such as the early implementation
      of new drug candidates and corresponding metabolites into routine doping control
      assays, even though these drug candidates are to date not approved for human use.
      Beyond this, analytical data are also cornerstones of investigations into
      atypical or adverse analytical findings, where the overall picture provides ample
      reason for follow-up studies. Such studies have been of most diverse nature, and
      tailored approaches have been required to probe hypotheses and scenarios reported
      by the involved parties concerning the plausibility and consistency of statements
      and (analytical) facts. In order to outline the variety of challenges that doping
      control laboratories are facing besides providing optimal detection capabilities
      and analytical comprehensiveness, selected case vignettes involving the follow-up
      of unconventional adverse analytical findings, urine sample manipulation,
      drug/food contamination issues, and unexpected biotransformation reactions are
      thematized.

PMID- 29445831
TI  - Using a sequential explanatory mixed method to evaluate the therapeutic window of
      opportunity for initiating osteoporosis treatment following fragility fractures.
AB  - : Interventions targeting patients with recent fragility fracture and their
      physician were most successful at initiating osteoporosis treatment during the
      first 12 months. This window of opportunity had already closed after 1 year. The
      reasons for declining or accepting the intensive intervention were explored in
      patients still untreated at 12 months. INTRODUCTION: A fragility fracture (FF)
      event identifies patients most likely to benefit from osteoporosis treatment.
      Nonetheless, most FF patients go untreated. Our objective was to determine how
      long an incident FF remains a strong incentive to initiate osteoporosis
      treatment. METHODS: A total of 1086 men and women over age 50 with a recent FF
      event were assigned to either standard care (SC), to minimal (MIN), or intensive
      (INT) interventions targeting patients and their family physician to initiate
      osteoporosis treatment. Inpatients with FF (mainly hip) evaluated by
      rheumatologists were also included in a specialized group (SPE; n = 324). At 1
      year, untreated patients in both the SC and the MIN groups were offered an INT
      intervention. The cohort was followed through 48 months. A qualitative analysis
      of patient-centered decision-making associated with initiation of treatment was
      conducted. RESULTS: In MIN and INT groups, osteoporosis treatment was initiated
      in 41.0 and 54.3% of untreated patients by 12 months, respectively, compared to
      68.4% in SPE and 18.9% in SC groups; initiation rates drastically dropped
      thereafter. Over 4863 patient-years of follow-up, the rates of new FF were 3.4
      per 100 patient-years, without significant differences between patients with
      initial major or minor FF, nor between control or intervention groups. Failure by
      patients and physicians to recognize FF as a sign of underlying bone disease
      contributed the most to lack of treatment. CONCLUSION: While incident FFs are an
      ideal opportunity for starting osteoporosis treatment, 1 year later, the
      therapeutic window of opportunity has already closed.

PMID- 29445833
TI  - Functionalized Au@Ag-Au nanoparticles as an optical and SERS dual probe for
      lateral flow sensing.
AB  - Lateral flow assay strips (LFASs) with Au nanoparticles (NPs) have been widely
      used as a probe for biomarkers in point-of-care testing; however, there still
      remain challenges in detection sensitivity and quantitative analysis. In this
      study, we developed a surface-enhanced Raman scattering (SERS)-based LFAS for
      quantitative analysis of a biomarker in the low concentration range. Moreover,
      apart from conventional Au NPs, three other types of citrate-capped Au-Ag
      bimetallic NPs: Au core with Ag shell NPs (Au@Ag NPs), rattle-like Au core in Ag
      Au shell NPs (Au@Ag-Au NPs) and Ag-Au NPs were prepared and functionalized, and
      their solution-based SERS activities were comprehensively studied by experimental
      measurement and theoretical analysis. The results clearly indicated that the
      citrate-capped Au@Ag-Au NPs exhibited the highest SERS activity among the probes
      tested. Au@Ag-Au NPs were used as both optical and SERS probes in a SERS-based
      LFAS. In the presence of the analyte at high concentrations, a purple color
      appeared in the test zone. Highly sensitive and quantitative analysis was
      realized by measurement of SERS signals from the test lines. One of the most
      specific markers for cardiac injury, cardiac troponin I (cTnI), was chosen as the
      detection model. The detection limit of the SERS-based LFAS for cardiac troponin
      I was 0.09 ng/mL, lowered by nearly 50 times compared with visual results, and
      could be further lowered by optimization. These results demonstrated that the
      SERS-based LFAS using citrate-capped Au@Ag-Au NPs as probes can be a powerful
      tool for highly sensitive and quantitative detection of biomarkers. Graphical
      abstract A surface-enhanced Raman scattering (SERS)-based lateral flow assay
      strip using rattle-like Au core in Ag-Au shell (Au@Ag-Au) nanoparticles as probes
      was developed for quantitative analysis of a biomarker, with a detection limit
      nearly 50 times lower than that of visual assessment. C control line, T test
      line.

PMID- 29445834
TI  - The combination of 2,5-dihydroxybenzoic acid and 2,5-dihydroxyacetophenone
      matrices for unequivocal assignment of phosphatidylethanolamine species in
      complex mixtures.
AB  - Unequivocal assignment of phospholipid peaks in complex mixtures is difficult if
      only the m/z values but no tandem mass spectrometry (MS/MS) data are available.
      This is usually the case for matrix-assisted laser/desorption ionization time-of
      flight (MALDI-TOF) MS imaging experiments and the analysis has normally to be
      performed without prior separation. Another problem might be the often matrix
      induced loss of one methyl group in phosphatidylcholine (PC) species, which makes
      them detectable as negative ions becoming isomers of some
      phosphatidylethanolamines (PEs). Selected lipid mixtures of known compositions
      were investigated by negative ion MALDI-TOF MS and various imaging experiments.
      In addition to common matrices such as 2,5-dihydroxybenzoic acid (DHB) and 9
      aminoacridine (9-AA), different binary matrices, including 2,5
      dihydroxyacetophenone (2,5-DHAP) as matrix additive to DHB, were tested to probe
      their performance in both ionization modes. Beside artificial PC and PE mixtures
      of known compositions, egg yolk and liver extracts as well as cryosections from
      liver and pancreas tissue were selected as biologically relevant systems. The
      majority of the binary MALDI matrices used here leads to the loss of a methyl
      group from PC in the negative ion mode, which makes the clear identification of
      PE species ambiguous. However, this problem does not apply if a mixture of DHB
      and 2,5-DHAP is used. Therefore, the application of DHB/2,5-DHAP as matrix is a
      simple method to unequivocally identify PEs even in complex mixtures and tissue
      sections as negative ions and without the necessity to separate the individual
      lipid classes prior to MS detection. Graphical abstract Many common MALDI
      matrices (such as 9-AA) induce the loss of a methyl group from PC rendering the
      PC detectable as negative ion. These ions (m/z 744.6 in the upper trace)
      represent isomers of typical PE species. It will be shown that this problem can
      be avoided if mixtures between DHB and 2,5-DHAP are applied. At these conditions,
      POPC is exclusively detectable as a matrix adduct with DHB (at m/z 912.6, lower
      trace) and does not interfere with PE. This approach can also be used in MALDI MS
      imaging.

PMID- 29445835
TI  - Application and evaluation of a high-resolution mass spectrometry screening
      method for veterinary drug residues in incurred fish and imported aquaculture
      samples.
AB  - The ability to detect chemical contaminants, including veterinary drug residues
      in animal products such as fish, is an important example of food safety analysis.
      In this paper, a liquid chromatography high-resolution mass spectrometry (LC
      HRMS) screening method using a quadrupole-Orbitrap instrument was applied to the
      analysis of veterinary drug residues in incurred tissues from aquacultured
      channel catfish, rainbow trout, and Atlantic salmon and imported aquacultured
      products including European eel, yellow croaker, and tilapia. Compared to
      traditional MS methods, the use of HRMS with nontargeted data acquisition and
      exact mass measurement capability greatly increased the scope of compounds that
      could be monitored simultaneously. The fish samples were prepared for analysis
      using a simple efficient procedure that consisted of an acidic acetonitrile
      extraction followed by solid phase extraction cleanup. Two different HRMS
      acquisition programs were used to analyze the fish extracts. This method detected
      and identified veterinary drugs including quinolones, fluoroquinolones,
      avermectins, dyes, and aminopenicillins at residue levels in fish that had been
      dosed with those compounds. A metabolite of amoxicillin, amoxicillin diketone,
      was also found at high levels in catfish, trout, and salmon. The method was also
      used to characterize drug residues in imported fish. In addition to confirming
      findings of fluoroquinolone and sulfonamide residues that were found by
      traditional targeted MS methods, several new compounds including 2-amino
      mebendazole in eel and ofloxacin in croaker were detected and identified.
      Graphical Abstract Aquacultured samples are analyzed with a high-resolution mass
      spectrometry screening method to detect and identify unusual veterinary drug
      residues including ofloxacin in an imported fish.

PMID- 29445836
TI  - Bone Loss After Romosozumab/Denosumab: Effects of Bisphosphonates.
AB  - Romosozumab and denosumab are monoclonal antibodies for the treatment of
      osteoporosis. Both have a rapid offset of effect resulting in loss of bone
      density (BMD) gained on-treatment and, in some cases, multiple vertebral
      fractures following treatment cessation. We recently reported disappointing
      results from transitioning patients from denosumab to intravenous zoledronate at
      the time the next denosumab injection is due. The present report re-assesses the
      role of bisphosphonates following the use of denosumab. In the FRAME trial,
      osteoporotic women were randomized to romosozumab or placebo for 1 year, then
      both groups were provided with open-label denosumab for the subsequent 2 years.
      In women completing this study at our center, we offered treatment with either
      oral or intravenous bisphosphonates. In the eleven women opting for intravenous
      treatment, zoledronate was given after a median delay of 65 days from trial-end,
      in the hope that this might increase skeletal uptake of the drug and, thereby,
      its efficacy to maintain bone density. In these women, spine BMD was 17.3% above
      baseline at trial-end, and still 12.3% above baseline a year later, a 73% (CI:
      61%, 85%) retention of the treatment benefit. The comparable BMD figures for the
      total hip were 10.7 and 9.2% above baseline, a 87% (CI: 77%, 98%) retention of
      treatment effect. In contrast, those not receiving treatment after the conclusion
      of the FRAME trial lost 80-90% of the BMD gained on-trial in the following 12
      months. Women treated with risedronate showed an intermediate response. In the
      zoledronate group, mean PINP 6 months post-FRAME was 23 +/- 4 ug/L and at 12
      months it was 47 +/- 8 ug/L, suggesting that repeat zoledronate dosing is needed
      at 1 year to maintain the BMD gains. In conclusion, delaying administration of
      intravenous bisphosphonate when transitioning from short-term denosumab appears
      to increase the extent to which the gains in BMD are maintained.

PMID- 29445837
TI  - Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone
      Disorders.
AB  - Alkaline phosphatases (APs) remove the phosphate (dephosphorylation) needed in
      multiple metabolic processes (from many molecules such as proteins, nucleotides,
      or pyrophosphate). Therefore, APs are important for bone mineralization but
      paradoxically they can also be deleterious for other processes, such as vascular
      calcification and the increasingly known cross-talk between bone and vessels. A
      proper balance between beneficial and harmful activities is further complicated
      in the context of chronic kidney disease (CKD). In this narrative review, we will
      briefly update the complexity of the enzyme, including its different isoforms
      such as the bone-specific alkaline phosphatase or the most recently discovered
      B1x. We will also analyze the correlations and potential discrepancies with
      parathyroid hormone and bone turnover and, most importantly, the valuable recent
      associations of AP's with cardiovascular disease and/or vascular calcification,
      and survival. Finally, a basic knowledge of the synthetic and degradation
      pathways of APs promises to open new therapeutic strategies for the treatment of
      the CKD-Mineral and Bone Disorder (CKD-MBD) in the near future, as well as for
      other processes such as sepsis, acute kidney injury, inflammation, endothelial
      dysfunction, metabolic syndrome or, in diabetes, cardiovascular complications.
      However, no studies have been done using APs as a primary therapeutic target for
      clinical outcomes, and therefore, AP's levels cannot yet be used alone as an
      isolated primary target in the treatment of CKD-MBD. Nonetheless, its diagnostic
      and prognostic potential should be underlined.

PMID- 29445838
TI  - Psychedelics and related drugs: therapeutic possibilities, mechanisms and
      regulation.

PMID- 29445839
TI  - Vocalization as a novel endpoint of atypical attachment behavior in 2,3,7,8
      tetrachlorodibenzo-p-dioxin-exposed infant mice.
AB  - Mammalian attachment behaviors, such as crying, are essential for infant survival
      by receiving food, protection, and warmth from caregivers. Ultrasonic
      vocalization (USV) of infant rodents functions to promote maternal proximity.
      Impaired USV emission has been reported in mouse models of autism spectrum
      disorder, suggesting that USV is associated with higher brain function. In utero
      and lactational dioxin exposure is known to induce higher brain function
      abnormalities in adulthood; however, whether perinatal dioxin exposure affects
      behavior during infancy is unclear. Therefore, we studied the impact of dioxin
      exposure on USV emission in infant mice born to dams treated with 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD; 0.6 or 3.0 ug/kg) on gestational day 12.5. On
      postnatal days 3-9, USVs of the offspring were recorded for 1 min using a
      microphone in a sound-attenuated chamber. The total USV and mean call durations
      in infant mice exposed to 3.0 ug/kg, but not 0.6 ug/kg, were shorter than those
      in the control mice. In addition, the percentages of complicated call types
      (i.e., chevron and wave) in mice exposed to 3.0 ug/kg were decreased. Dioxin
      induced gene expression changes occurred in the brains of mice exposed to 3.0
      ug/kg; however, body weight, motor activity, and vocal fold structure were not
      significantly affected. These results suggest that infant USV is a useful
      behavioral endpoint in developmental neurotoxicity assessment that may be used to
      evaluate effects of chemical exposure on the infant-caregiver interaction.

PMID- 29445840
TI  - [Serious adverse events in clinical trials with TAVR and SAVR].
AB  - BACKGROUND: The expansion of the transcatheter aortic valve replacement (TAVR)
      indication towards patients with intermediate surgical risk (Ref. Society of
      Thoracic Surgeons, STS, score) was analyzed. The aim was to investigate if the
      complication rates particularly with respect to TAVR and surgical aortic valve
      replacement (SAVR) concerning patients with intermediate risk are comparable.
      METHODS: An analysis of serious adverse events (SAEs) and complication rates in
      clinical trials with TAVR and SAVR of these patients in comparison with high
      surgical risk patients was performed with the scientific literature and in the
      Federal Institute for Drugs and Medical Devices (Bundesinstitut fur Arzneimittel
      und Medizinprodukte, BfArM) database (2012-2017). RESULTS: In several studies for
      intermediate-risk TAVR patients the published data showed that some complication
      rates (e. g. mortality) are comparable or better than for intermediate-risk SAVR
      patients. The analysis of the BfArM database in study 1 (TAVR) resulted in a
      lower all-cause mortality for intermediate-risk patients (0.9% at 30 days and
      7.3% at 1 year post-procedure) than concerning high-risk patients (5.2% at 30
      days and 15.7% at 1 year post-procedure). In study 1 the cardiovascular mortality
      was altogether 11.5% at 4 years post-procedure (9.2% for intermediate and 13.4%
      for high-risk patients), in study 2 (patients with high-risk) at 4 years it was
      15.5% in the TAVR group with slightly lower cardiovascular mortality for SAVR
      patients with 14.8%. CONCLUSION: In the analysis TAVR interventions have
      favorable incidences concerning mortality (all-cause and cardiovascular) for
      intermediate-risk patients. Recently, a transcatheter aortic heart valve with
      this expanded risk indication received a CE label for the first time in Europe;
      however, the results of larger clinical studies are relevant for the evaluation
      (e. g. long-term function over more than 5 years) of TAVR valves for intermediate
      risk patients.

PMID- 29445842
TI  - [Rare diseases in dentistry and oral medicine : Report on the 2017 first national
      congress].
AB  - On November 25, the first national congress for rare diseases in dentistry and
      oral medicine under the auspices of ACHSE e. V. and Orphanet was held in
      Muenster. With speakers from the field of medicine, dentistry, politics, patient
      advocacy groups, self-help groups and persons concerned, a platform for exchange
      between physicians and patients on an equal footing was offered to the
      participants. At the end of each of the 12 lectures, more than 300 national and
      international guests discussed the various issues and perspectives related to the
      topic of rare diseases in dentistry and oral medicine. Besides the different
      presentations focusing on dentistry, neuropediatrics, and human genetics, the
      existing centers for rare diseases, sources of information, European reference
      networks, and the national action plan for people with rare diseases were the
      subjects of intensive discussion. The patient perspective was also considered.
      From now on the congress shall be held in Muenster biennially.

PMID- 29445841
TI  - Folding and assembly defects of pyruvate dehydrogenase deficiency-related
      variants in the E1alpha subunit of the pyruvate dehydrogenase complex.
AB  - The pyruvate dehydrogenase complex (PDC) bridges glycolysis and the citric acid
      cycle. In human, PDC deficiency leads to severe neurodevelopmental delay and
      progressive neurodegeneration. The majority of cases are caused by variants in
      the gene encoding the PDC subunit E1alpha. The molecular effects of the variants,
      however, remain poorly understood. Using yeast as a eukaryotic model system, we
      have studied the substitutions A189V, M230V, and R322C in yeast E1alpha
      (corresponding to the pathogenic variants A169V, M210V, and R302C in human
      E1alpha) and evaluated how substitutions of single amino acid residues within
      different functional E1alpha regions affect PDC structure and activity. The
      E1alpha A189V substitution located in the heterodimer interface showed a more
      compact conformation with significant underrepresentation of E1 in PDC and
      impaired overall PDC activity. The E1alpha M230V substitution located in the
      tetramer and heterodimer interface showed a relatively more open conformation and
      was particularly affected by low thiamin pyrophosphate concentrations. The
      E1alpha R322C substitution located in the phosphorylation loop of E1alpha
      resulted in PDC lacking E3 subunits and abolished overall functional activity.
      Furthermore, we show for the E1alpha variant A189V that variant E1alpha
      accumulates in the Hsp60 chaperonin, but can be released upon ATP
      supplementation. Our studies suggest that pathogenic E1alpha variants may be
      associated with structural changes of PDC and impaired folding of E1alpha.

PMID- 29445843
TI  - Realignment surgery in adult spinal deformity : Prevalence and risk factors for
      proximal junctional kyphosis.
AB  - Although surgical techniques pertaining to adult spinal deformity (ASD) have
      advanced over the last decade, proximal junctional kyphosis (PJK) is still a
      complication following surgery for ASD that continues to significantly challenge
      clinicians. This article aimed to report on the prevalence of PJK as well as
      enhance understanding of surgically modifiable and non-modifiable risk factors of
      PJK to guide management of this postoperative complication of ASD. As the
      understanding of the pathogenesis as well as surgical modifications aimed at
      reducing the incidence of PJK have advanced, so too should clinicians' ability to
      implement more patient-specific operative plans and improve outcomes following
      realignment surgery for ASD.

PMID- 29445844
TI  - Accuracy of genomic selection to predict maize single-crosses obtained through
      different mating designs.
AB  - KEY MESSAGE: Testcross is the worst mating design to use as a training set to
      predict maize single-crosses that would be obtained through full diallel or North
      Carolina design II. Even though many papers have been published about genomic
      prediction (GP) in maize, the best mating design to build the training population
      has not been defined yet. Such design must maximize the accuracy given
      constraints on costs and on the logistics of the crosses to be made. Hence, the
      aims of this work were: (1) empirically evaluate the effect of the mating
      designs, used as training set, on genomic selection to predict maize single
      crosses obtained through full diallel and North Carolina design II, (2) and
      identify the possibility of reducing the number of crosses and parents to compose
      these training sets. Our results suggest that testcross is the worst mating
      design to use as a training set to predict maize single-crosses that would be
      obtained through full diallel or North Carolina design II. Moreover, North
      Carolina design II is the best training set to predict hybrids taken from full
      diallel. However, hybrids from full diallel and North Carolina design II can be
      well predicted using optimized training sets, which also allow reducing the total
      number of crosses to be made. Nevertheless, the number of parents and the crosses
      per parent in the training sets should be maximized.

PMID- 29445845
TI  - Prospective randomised controlled trial of written supplement to verbal
      communication of results to patients at the time of flexible cystoscopy.
AB  - PURPOSE: This trial assessed if written information on procedural findings and
      subsequent treatment improved understanding and reduced anxiety among patients
      undergoing day case flexible cystoscopy (FC). METHODS: Participants completed pre
      and post-procedure questionnaires self-rating anxiety and feeling well informed
      on 5-point Likert scales. Supplemental written information was provided after FC
      to half the patients on a standardized template, according to randomized
      allocation. Comparisons between the groups were undertaken using the Wilcoxon
      test. RESULTS: Two hundred patients were recruited, with 171 evaluable
      questionnaires (83 from written group). The distribution of age, sex and prior
      FC, as well as the pre-procedure self-assessment of anxiety and understanding,
      was similar between the two groups. Patients receiving written information
      reported feeling better informed, with median (range) Likert score of 5 (4-5)
      compared to 4 (1-5) out of 5 (p < 0.0001) and less anxious (score 1 [1-4]
      compared to 2 [1-5] out of 5, p < 0.005), although all except four patients had
      an accurate understanding of the information provided (p = NS). CONCLUSIONS:
      Written information at the time of FC leads to patients feeling better informed
      and less anxious, although verbal information alone appears to lead to an
      adequate understanding. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12616000288426.

PMID- 29445847
TI  - Correction to: Cryptosporidium Spp. Contamination in Perna perna Mussels Destined
      for Human Consumption in Southeastern Rio de Janeiro, Brazil.
AB  - The original version of this article unfortunately contained a mistake.

PMID- 29445846
TI  - Prostatic artery embolization for benign prostatic obstruction: assessment of
      safety and efficacy.
AB  - PURPOSE: Prostatic artery embolization (PAE) has seen a recent increase in
      interest as a treatment for men with benign prostatic obstruction (BPO). The
      appeal of this intervention lies in reported reduction in morbidity and its
      minimally invasive nature. The purpose of this review is to assess the safety and
      efficacy of PAE as a new treatment in BPO and explore risks surrounding its
      performance. METHODS: A review of the literature was performed. Medical databases
      searched included PubMed, EMBASE, and Cochrane databases, limited to English,
      peer-reviewed articles. Search terms included prostatic artery embolization,
      lower urinary tracts symptoms, minimally invasive therapies, interventional
      radiology prostate, and benign prostatic hyperplasia. Articles were screened by
      two independent reviewers for content on development, methods, outcomes, and
      complications of PAE. RESULTS: Suitability of patients to undergo PAE depends on
      review of patient history, pre-procedure visualisation of appropriate vascular
      anatomy and clinical parameters. Despite this selection of candidates favourable
      for procedural success, PAE is not without risk of complications, some of which
      can significantly affect patient quality of life. CONCLUSIONS: Although initial
      findings show promise regarding safety and efficacy of PAE in improving symptom
      and quality-of-life scores, further investigation is required to establish
      durability of effect and the appropriate use of this experimental modality. There
      is currently limited robust evidence for the beneficial outcomes of PAE. Long
      term follow-up studies will add to the evidence base to help further assess the
      feasibility of this procedure as an alternative to TURP.

PMID- 29445848
TI  - Characterization and Local Emission Sources for Ammonia in an Urban Environment.
AB  - Ammonia levels were evaluated in the urban environment of Madrid City, Spain. A
      total of 110 samplers were distributed throughout the city. Vehicle traffic
      density, garbage containers and sewers were identified as local emission sources
      of ammonia. The average ammonia concentrations were 4.66 +/- 2.14 ug/m3 (0.39
      11.23 ug/m3 range) in the winter and 5.30 +/- 1.81 ug/m3 (2.33-11.08 ug/m3 range)
      in the summer. Spatial and seasonal variations of ammonia levels were evaluated.
      Hotspots were located in the south and center of Madrid City in both winter and
      summer seasons, with lower ammonia concentrations located in the north (winter)
      and in the west and east (summer). The number of representative points that were
      needed to establish a reliable air quality monitoring network for ammonia was
      determined using a combined clustering and kriging approach. The results
      indicated that 40 samplers were sufficient to provide a reliable estimate for
      Madrid City.

PMID- 29445849
TI  - Tissue-Specific Antioxidative Responses and Cadmium Accumulation in Silurus
      meridionalis Under Chronic Waterborne Cadmium Exposure.
AB  - In this study, the oxidative damage, antioxidative responses and cadmium (Cd)
      accumulation in juvenile Silurus meridionalis were studied, after S. meridionalis
      were exposed to 0 (control), 62.5, 125, 250 and 500 ug Cd/L for 56 days. Cd
      accumulation, malondialdehyde, superoxide dismutase (SOD), catalase, glutathione
      (GSH) and total antioxidant capacity (T-AOC) were determined in gill, liver,
      kidney and intestine tissues. The results showed that the Cd accumulation in S.
      meridionalis was dose-dependent and tissue-specific, with the highest Cd content
      in the kidney, followed by the liver, gill, and intestine. Waterborne Cd stress
      in S. meridionalis was expressed as tissue-specific oxidative damage and
      antioxidant responses in gill, liver, kidney and intestine tissues. Waterborne Cd
      exposure induced the most significant oxidative damage in the gill, followed by
      the liver and kidney, while the intestine showed no sensitivity to waterborne Cd
      exposure. The antioxidants, such as SOD in the liver, kidney and intestine, as
      well as T-AOC and GSH in the gill, liver and kidney, were sensitive to waterborne
      Cd exposure.

PMID- 29445850
TI  - Factors associated with household food insecurity and depression in pregnant
      South African women from a low socio-economic setting: a cross-sectional study.
AB  - PURPOSE: Food insecurity has been linked with maternal depression in low-income
      settings. Few studies have looked at factors associated with both food insecurity
      and maternal depression as outcomes. This study aimed to assess factors
      associated with food insecurity and depression in a sample of pregnant South
      African women. METHODS: We conducted a cross-sectional study at a Midwife
      Obstetric Unit in a low-income suburb in Cape Town. Pregnant women attending the
      clinic for their first antenatal visit were invited to participate. The shortened
      form of the US Household Food Security Survey Module was used to measure food
      insecurity. The Expanded Mini-International Neuropsychiatric Interview was used
      to diagnose depression, anxiety, alcohol and drug dependence, and assess for
      suicidal ideation and behaviour. Logistic regression modelling was conducted to
      explore factors associated with food insecurity and depression in separate
      models. RESULTS: We found that 42% of households were food insecure and that 21%
      of participants were depressed (N = 376). The odds of being food insecure were
      increased in women with suicidal behaviour (OR = 5.34; 95% CI 1.26-22.57), with
      depression (4.27; 1.43-12.70) and in those with three or more children (3.79;
      1.25-11.55). The odds of depression was greater in women who were food insecure
      (5.30; 1.63-17.30), substance dependent (15.83; 1.31-191.48) or diagnosed with an
      anxiety disorder (5.04; 1.71-14.82). CONCLUSIONS: Food insecurity and depression
      are strongly associated in pregnant women. The relationship between food
      insecurity and depression is complex and requires further investigation.
      Interventions that improve both food security and mental health during the
      perinatal period are likely to benefit the physical and mental well-being of
      mothers and children.

PMID- 29445851
TI  - Beta cell extracellular vesicle miR-21-5p cargo is increased in response to
      inflammatory cytokines and serves as a biomarker of type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Improved biomarkers are acutely needed for the detection of
      developing type 1 diabetes, prior to critical loss of beta cell mass. We
      previously demonstrated that elevated beta cell microRNA 21-5p (miR-21-5p) in
      rodent and human models of type 1 diabetes increased beta cell apoptosis. We
      hypothesised that the inflammatory milieu of developing diabetes may also
      increase miR-21-5p in beta cell extracellular vesicle (EV) cargo and that
      circulating EV miR-21-5p would be increased during type 1 diabetes development.
      METHODS: MIN6 and EndoC-betaH1 beta cell lines and human islets were treated with
      IL-1beta, IFN-gamma and TNF-alpha to mimic the inflammatory milieu of early type
      1 diabetes. Serum was collected weekly from 8-week-old female NOD mice until
      diabetes onset. Sera from a cross-section of 19 children at the time of type 1
      diabetes diagnosis and 16 healthy children were also analysed. EVs were isolated
      from cell culture media or serum using sequential ultracentrifugation or ExoQuick
      precipitation and EV miRNAs were assayed. RESULTS: Cytokine treatment in beta
      cell lines and human islets resulted in a 1.5- to threefold increase in miR-21
      5p. However, corresponding EVs were further enriched for this miRNA, with a three
      to sixfold EV miR-21-5p increase in response to cytokine treatment. This
      difference was only partially reduced by pre-treatment of beta cells with Z-VAD
      FMK to inhibit cytokine-induced caspase activity. Nanoparticle tracking analysis
      showed cytokines to have no effect on the number of EVs, implicating specific
      changes within EV cargo as being responsible for the increase in beta cell EV miR
      21-5p. Sequential ultracentrifugation to separate EVs by size suggested that this
      effect was mostly due to cytokine-induced increases in exosome miR-21-5p.
      Longitudinal serum collections from NOD mice showed that EVs displayed
      progressive increases in miR-21-5p beginning 3 weeks prior to diabetes onset. To
      validate the relevance to human diabetes, we assayed serum from children with new
      onset type 1 diabetes compared with healthy children. While total serum miR-21-5p
      and total serum EVs were reduced in diabetic participants, serum EV miR-21-5p was
      increased threefold compared with non-diabetic individuals. By contrast, both
      serum and EV miR-375-5p were increased in parallel among diabetic participants.
      CONCLUSIONS/INTERPRETATION: We propose that circulating EV miR-21-5p may be a
      promising marker of developing type 1 diabetes. Additionally, our findings
      highlight that, for certain miRNAs, total circulating miRNA levels are distinct
      from circulating EV miRNA content.

PMID- 29445852
TI  - [Patient education for adults with atopic dermatitis according to the ARNE
      concept].
AB  - Atopic dermatitis (AD) represents a chronic inflammatory skin disease showing a 1
      year prevalence of 2-3% during adulthood. In a national randomized, controlled
      multicenter study initiated by the "Arbeitsgemeinschaft Neurodermitisschulung im
      Erwachsenenalter" (ARNE, Working Group on Educational Training for Adults with
      Atopic Dermatitis) a program for structured patient education conducted by a
      multiprofessional team was developed and evaluated. At 1-year follow-up, coping
      behavior with respect to itch (assessed by the "Juckreiz-Kognitions-Fragebogen",
      p < 0.001) and in quality of life (Skindex-29, p < 0.001) significantly improved
      in patients who had participated in this 12 h patient educational program (n =
      168) compared to the waiting control group (n = 147). Moreover, the training led
      to a significantly greater reduction in disease severity (SCORAD Index, p <
      0.001). In this first randomized, controlled multicenter study on effects of
      patient education in adulthood AD, significant beneficial effects on both
      psychosocial parameters and the disease severity could be demonstrated.

PMID- 29445853
TI  - Xylo- and arabinoxylooligosaccharides from wheat bran by endoxylanases,
      utilisation by probiotic bacteria, and structural studies of the enzymes.
AB  - Xylooligosaccharides (XOS) and arabinoxylooligosaccharides (AXOS) were produced
      from the insoluble arabinoxylan fraction of pretreated wheat bran by
      endoxylanases. The glycoside hydrolase (GH) family 10 xylanases GsXyn10A from
      Geobacillus stearothermophilus and RmXyn10A-CM from Rhodothermus marinus produced
      the AXOS A3X, A2XX and A2 + 3XX in addition to XOS. RmXyn10A-CM also produced XA2
      + 3XX due to its non-conserved aglycone region accommodating additional arabinose
      substitutions in subsite +2. The GH11 enzymes, Pentopan from Thermomyces
      lanuginosus and NpXyn11A from Neocallimastix patriciarum had minor structural
      differences affecting hydrogen bonds in subsites -3 and +3, with similar
      hydrolysis profiles producing XA3XX as major AXOS and minor amounts of XA2XX but
      different ratios of X3/X2. In vitro analysis of the prebiotic properties of
      (A)XOS produced by Pentopan revealed nearly complete uptake of X2 and X3 by the
      probiotic bacteria Lactobacillus brevis and Bifidobacterium adolescentis. In
      contrast to previous reports, the GH43 arabinofuranosidase BaAXHd-3 from B.
      adolescentis cleaved alpha-1,3-linked arabinose on some single substituted AXOS.

PMID- 29445854
TI  - Constrained minimization problems for the reproduction number in meta-population
      models.
AB  - The basic reproduction number ([Formula: see text]) can be considerably higher in
      an SIR model with heterogeneous mixing compared to that from a corresponding
      model with homogeneous mixing. For example, in the case of measles, mumps and
      rubella in San Diego, CA, Glasser et al. (Lancet Infect Dis 16(5):599-605, 2016.
      https://doi.org/10.1016/S1473-3099(16)00004-9 ), reported an increase of 70% in
      [Formula: see text] when heterogeneity was accounted for. Meta-population models
      with simple heterogeneous mixing functions, e.g., proportionate mixing, have been
      employed to identify optimal vaccination strategies using an approach based on
      the gradient of the effective reproduction number ([Formula: see text]), which
      consists of partial derivatives of [Formula: see text] with respect to the
      proportions immune [Formula: see text] in sub-groups i (Feng et al. in J Theor
      Biol 386:177-187, 2015.  https://doi.org/10.1016/j.jtbi.2015.09.006 ; Math Biosci
      287:93-104, 2017.  https://doi.org/10.1016/j.mbs.2016.09.013 ). These papers
      consider cases in which an optimal vaccination strategy exists. However, in
      general, the optimal solution identified using the gradient may not be feasible
      for some parameter values (i.e., vaccination coverages outside the unit
      interval). In this paper, we derive the analytic conditions under which the
      optimal solution is feasible. Explicit expressions for the optimal solutions in
      the case of [Formula: see text] sub-populations are obtained, and the bounds for
      optimal solutions are derived for [Formula: see text] sub-populations. This is
      done for general mixing functions and examples of proportionate and preferential
      mixing are presented. Of special significance is the result that for general
      mixing schemes, both [Formula: see text] and [Formula: see text] are bounded
      below and above by their corresponding expressions when mixing is proportionate
      and isolated, respectively.

PMID- 29445855
TI  - [Treatment strategy for early stage rectal cancer (T1 carcinoma)].
AB  - BACKROUND: A common consensus for the definition for early rectal cancer does not
      exist. This item is used in cases of histological findings including pTis, pT1 or
      pT2 tumors. The term early rectal cancer is not mentioned in the German S3
      guidelines on colorectal cancer. The pTis tumors are located at the mucosa level
      of the intestinal wall and they have nearly no tendency to develop metastases but
      pT2 tumors have a high risk of local metastases; therefore, the term early rectal
      cancer is not adequate for pT2 tumors. OBJECTIVE: This focus of this article is
      exclusively on pT1 rectal cancer. Following the histological definition, pT1
      tumors of the rectum are located at the level of the mucosa and submucosa of the
      intestinal wall. CONCLUSION: With respect to the nature of the tumor (e.g. size,
      grading, invasion of lymphatic and/or blood vessels, Kikuchi classification)
      local methods (endoscopic procedure, surgical techniques) or radical resections
      are recommended. Tumor budding is of increasing interest and importance.
      Depending on the severity of the tumor budding classification (bd1-bd3) there is
      an association with a more frequent occurrence of lymph node metastases and
      should therefore be taken into consideration in treatment decisions in the
      future.

PMID- 29445856
TI  - [Rare cause of epigastric pain with spontaneous improvement without previous
      abdominal surgery].

PMID- 29445857
TI  - Superior and Anterior Hyoid Displacement During Swallowing in Non-Dysphagic
      Individuals.
AB  - The Dynamic Swallow Study (DSS) is a methodology used to objectively and
      quantitatively assess swallowing kinematics during Videofluoroscopic Swallow
      Studies (VFSS). No DSS normative data exist delineating superior and anterior
      hyoid displacement (Hsup and Hant, respectively), nor the ratio between Hsup and
      Hant (SAratio). The aims of this study were to (1) establish normative data for
      Hsup, Hant, and SAratio and (2) assess the effects of age, sex, and bolus size on
      these measures in non-dysphagic patients, within the context of DSS. VFSSs were
      reviewed for consecutive elderly (>= 65 years) and non-elderly (< 65 years) male
      and female non-dysphagic patients. Measurements of Hsup, Hant, and SAratio were
      made using a novel measurement methodology within the context of the Dynamic
      Swallow Study (DSS) protocol. Statistical analysis was performed to establish
      interaction effects and main effects of age, sex, and bolus size on Hsup, Hant,
      and SAratio. Descriptive statistics (mean +/- standard deviations) are outlined
      for Hsup, Hant, and SAratio. Hsup was significantly effected by bolus size and
      age. Additionally, a significant three-way interaction of age, sex, and bolus
      size was observed. Hant was significantly effected by bolus size and sex, but no
      two- or three-way interactions were present. Neither bolus size, age, nor sex
      significantly effected SAratio. Age, sex, and bolus size normative data were
      established for Hsup, Hant, and SAratio for VFSS kinematic analysis. By outlining
      these measures, one can more thoroughly evaluate the areas of specific swallowing
      impairment, better determine the therapy targets, and track changes over time.

PMID- 29445858
TI  - L-Thyroxine intake as a potential risk factor for the development of fatigue in
      breast cancer patients undergoing chemotherapy.
AB  - PURPOSE: L-Thyroxine is one of the most commonly prescribed drugs and accordingly
      used by many breast cancer patients with thyroid disorders. Hence, potential
      interactions of chemotherapy with L-thyroxine, possibly contributing to fatigue,
      would be of high clinical relevance. Therefore, we investigated fatigue and
      underlying pathways in L-thyroxine-using breast cancer patients during
      chemotherapy. METHODS: Thyroid-stimulating hormone (TSH), L-triiodothyronine
      (T3), and diurnal salivary cortisol patterns were analyzed in breast cancer
      patients in the beginning and at the end of adjuvant chemotherapy within the
      control group (n = 41) of a randomized exercise intervention trial. Additionally,
      relationships in the exercising group (n = 45) as well as in healthy women (n =
      25) were explored. Regression and mediation analyses were performed. RESULTS: L
      Thyroxine use was significantly associated with lower TSH (median = 0.33 mU/l,
      interquartile range = (0.15-0.48)), whereas patients not using L-thyroxine had
      TSH comparable to healthy women (0.51 mU/l (0.37-0.74)). T3 significantly
      declined during chemotherapy in L-thyroxine users but not in non-users. However,
      the group difference failed statistical significance. L-Thyroxine treatment was
      significantly associated with increased physical fatigue during chemotherapy (p =
      0.004) in the non-exercising group. This association appeared to be partly
      mediated by TSH. Further, TSH appeared to affect fatigue partly via increased
      cortisol levels. In the exercise group, there was no significant association
      between L-thyroxine and fatigue. CONCLUSIONS: L-Thyroxine treatment during
      chemotherapy might result in hormonal dysregulations that can contribute to
      increased physical fatigue. Therefore, breast cancer patients on L-thyroxine
      treatment may need special monitoring of their thyroid levels and of fatigue
      during chemotherapy and should be encouraged to exercise. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01106820.

PMID- 29445859
TI  - A new species of Stilestrongylus (Nematoda, Heligmonellidae) from the Atlantic
      Forest of Misiones, Argentina, parasitic in Euryoryzomys russatus (Cricetidae,
      Sigmodontinae).
AB  - A new species of Heligmonellidae (Trichostrongylina, Heligmosomoidea),
      Stilestrongylus kaaguyporai n. sp. is described from the small intestine of
      Euryoryzomys russatus (Rodentia, Cricetidae, Sigmodontinae) from the Argentine
      Atlantic Forest, in the Misiones province. The new species was found at Campo
      Anexo Manuel Belgrano, Reserva de Vida Silvestre Urugua-i and Parque Provincial
      Urugua-i, with a prevalence of 73% in 15 hosts examined. Stilestrongylus includes
      24 Neotropical species, all parasitic in rodents, mostly Sigmodontinae.
      Stilestrongylus kaaguyporai n. sp. can be differentiated from its congeners by
      the following characters: caudal bursa dissymmetrical with right lobe larger and
      pattern of type1-4 in both lobes, rays 6 not forming a lateral trident with rays
      4 and 5, rays 8 with dissymmetrical pathway, genital cone hypertrophied with a
      conspicuous hood-like projection and females with a marked dorso-ventral torsion
      of the posterior end. This report is the second record of a Stilestrongylus
      species in E. russatus, increasing to nine the number of parasitic species known
      from this host.

PMID- 29445860
TI  - Origin and initiation mechanisms of neuroblastoma.
AB  - Neuroblastoma is an embryonal malignancy that affects normal development of the
      adrenal medulla and paravertebral sympathetic ganglia in early childhood.
      Extensive studies have revealed the molecular characteristics of human
      neuroblastomas, including abnormalities at genome, epigenome and transcriptome
      levels. However, neuroblastoma initiation mechanisms and even its origin are long
      standing mysteries. In this review article, we summarize the current knowledge
      about normal development of putative neuroblastoma sources, namely
      sympathoadrenal lineage of neural crest cells and Schwann cell precursors that
      were recently identified as the source of adrenal chromaffin cells. A plausible
      origin of enigmatic stage 4S neuroblastoma is also discussed. With regard to the
      initiation mechanisms, we review genetic abnormalities in neuroblastomas and
      their possible association to initiation mechanisms. We also summarize evidences
      of neuroblastoma initiation observed in genetically engineered animal models, in
      which epigenetic alterations were involved, including transcriptomic upregulation
      by N-Myc and downregulation by polycomb repressive complex 2. Finally, several in
      vitro experimental methods are proposed that hopefully will accelerate our
      comprehension of neuroblastoma initiation. Thus, this review summarizes the state
      of-the-art knowledge about the mechanisms of neuroblastoma initiation, which is
      critical for developing new strategies to cure children with neuroblastoma.

PMID- 29445861
TI  - Bovine neutrophils in health and disease.
AB  - Bovine neutrophils have similarities to those of other species with respect to
      mechanisms of their activation and migration into tissue, modulation of immune
      responses and the balance between microbial killing and host tissue damage.
      However, bovine neutrophils have biochemical and functional differences from
      those of other species, which may yield insights about the comparative biology of
      neutrophils. Neutrophils play protective and harmful roles in the infectious
      diseases of cattle that occur at times of transition: respiratory disease in beef
      calves recently arrived to feedlots and mastitis and other diseases of
      postparturient dairy cows. An important research focus is the mechanisms by which
      risk factors for these diseases affect neutrophil function and thereby lead to
      disease and the prospect of genetic or pharmacologic improvement of disease
      resistance. Further, in keeping with the One Health paradigm, cattle can be
      considered a model for studying the role of neutrophils in naturally occurring
      diseases caused by host-adapted pathogens and are thus an intermediary between
      studies of mouse models and investigations of human disease. Finally, the study
      of bovine neutrophils is important for agriculture, to understand the
      pathogenesis of these production-limiting diseases and to develop novel methods
      of disease prevention that improve animal health and reduce the reliance on
      antimicrobial use.

PMID- 29445862
TI  - Hydrodynamic performance of a single-use aerated stirred bioreactor in animal
      cell culture: applications of tomography, dynamic gas disengagement (DGD), and
      CFD.
AB  - The hydrodynamics of gas-liquid two-phase flow in a single-use bioreactor were
      investigated in detail both experimentally and numerically. Electrical resistance
      tomography (ERT) and dynamic gas disengagement (DGD) combined with computational
      fluid dynamics (CFD) were employed to assess the effect of the volumetric gas
      flow rate and impeller speed on the gas-liquid flow field, local and global gas
      holdup values, and Sauter mean bubble diameter. From the results obtained from
      DGD coupled with ERT, the bubble sizes were determined. The experimental data
      indicated that the total gas holdup values increased with increasing both the
      rotational speed of impeller and volumetric gas flow rate. Moreover, the analysis
      of the flow field generated inside the aerated stirred bioreactor was conducted
      using CFD results. Overall, a more uniform distribution of the gas holdup was
      obtained at impeller speeds >= 100 rpm for volumetric gas flow rates >= 1.6 * 10
      5 m3/s.

PMID- 29445863
TI  - Use of biological disease modifying antirheumatic drugs in rheumatoid arthritis
      in Austria from 2008 to 2011 : A retrospective analysis of 72% of the population.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory
      joint disease. On a national level in Austria, there are currently no data
      available on how often and which biological disease modifying antirheumatic drugs
      (bDMARDs) are prescribed in patients with RA. The aim of the present study was to
      explore prescription patterns of bDMARDs in RA in Austria with a focus on drug
      survival. METHODS: A retrospective data analysis of bDMARD courses of individual
      patients with RA that were extracted from the databases of nine Austrian health
      insurance funds covering 6.1 million (72%) insured people in a 4-year observation
      period from January 2008 to December 2011. Only patients with first prescriptions
      of bDMARDs were included. All patients with diagnoses other than RA were
      excluded. RESULTS: A total of 2906 first prescriptions of bDMARDs were included
      in the present analysis and 19.35% of RA patients were on bDMARDs in Austria
      taking into account a prevalence of RA of 0.5%. Tocilizumab showed the longest
      drug survival after 1 year (73.2%), followed by abatacept which had the longest
      drug survival after 2 (68.2%) and 3 years (65.2%). The most frequent second
      bDMARDs switched to were adalimumab (n = 109, 26%), tocilizumab (n = 83, 20%) and
      etanercept (n = 82, 20%) and 37% of biological DMARDs were prescribed as
      monotherapy (ranging from 33% with infliximab to 46% with tocilizumab).
      CONCLUSIONS: Our analysis is based on the largest health care database available
      in Austria. Tocilizumab and abatacept showed the longest drug survival.
      Adalimumab, tocilizumab and etanercept were the most frequent DMARDs switched to.
      Of interest was the high number of bDMARD monotherapies.

PMID- 29445864
TI  - Playing to your skills: a randomised controlled trial evaluating a dedicated
      video game for minimally invasive surgery.
AB  - BACKGROUND: Video gaming demands elements of visual attention, hand-eye
      coordination and depth perception which may be contiguous with laparoscopic skill
      development. General video gaming has demonstrated altered cortical plasticity
      and improved baseline/acquisition of minimally invasive skills. The present study
      aimed to evaluate for skill acquisition associated with a commercially available
      dedicated laparoscopic video game (Underground) and its unique (laparoscopic
      like) controller for the Nintendo(r)Wii UTM console. METHODS: This single-blinded
      randomised controlled study was conducted with laparoscopically naive student
      volunteers of limited (< 3 h/week) video gaming backgrounds. Baseline
      laparoscopic skills were assessed using four basic tasks on the Virtual Reality
      (VR) simulator (LAP MentorTM, 3D systems, Colorado, USA). Twenty participants
      were randomised to two groups; Group A was requested to complete 5 h of video
      gaming (Underground) per week and Group B to avoid gaming beyond their normal
      frequency. After 4 weeks participants were reassessed using the same VR tasks.
      Changes in simulator performances were assessed for each group and for intergroup
      variances using mixed model regression. RESULTS: Significant inter- and
      intragroup performances were present for the video gaming and controls across
      four basic tasks. The video gaming group demonstrated significant improvements in
      thirty-one of the metrics examined including dominant (p <= 0.004) and non
      dominant (p < 0.050) instrument movements, pathlengths (p <= 0.040), time taken
      (p <= 0.021) and end score [p <= 0.046, (task-dependent)]. The control group
      demonstrated improvements in fourteen measures. The video gaming group
      demonstrated significant (p < 0.05) improvements compared to the control in five
      metrics. Despite encouraged gameplay and the console in participants' domiciles,
      voluntary engagement was lower than directed due to factors including: game
      enjoyment (33.3%), lack of available time (22.2%) and entertainment distractions
      (11.1%). CONCLUSION: Our work revealed significant value in training using a
      dedicated laparoscopic video game for acquisition of virtual laparoscopic skills.
      This novel serious game may provide foundations for future surgical developments
      on game consoles in the home environment.

PMID- 29445865
TI  - Risk of recurrence in a homogeneously managed pT3-differentiated thyroid
      carcinoma population.
AB  - BACKGROUND: International guidelines for the management of differentiated thyroid
      cancers are based on the 7th TNM classification: pT3 tumors are defined as
      differentiated thyroid cancers (DTCs) measuring more than 4 cm in their greatest
      dimension that are limited to the thyroid or any tumor with minimal
      extrathyroidal extension (ETE; sternothyroid muscle or perithyroid soft tissues).
      Differences in clinicohistological features and prognosis among patients with pT3
      tumors remain controversial, and studies regarding pT3 subgroups are lacking.
      OBJECTIVE: To analyze the prognosis of four subgroups of pT3 DTCs (papillary,
      PTC; or follicular, FTC). DESIGN AND SETTING: The data of patients who underwent
      surgery for pT3 DTC between 1978 and 2015 in a surgical department specialized in
      endocrine surgery were reviewed. Patients were classified into four groups as
      follows: the pT3a (<= 10 mm with ETE), pT3b (10-40 mm with ETE), pT3c (> 40 mm
      without ETE), and pT3d groups (> 40 mm with ETE). Recurrence-free survival (RFS)
      was analyzed using the Kaplan-Meier method. RESULTS: One thousand eighty-eight
      patients with pT3 DTC were included, of whom 311 (29%) had pT3a; 548 (50%), pT3b;
      165 (15%), pT3c; and 64 (6%), pT3d. For the 916 patients with lymph node (LN)
      dissection, metastatic LNs were more frequent in the pT3b and pT3d groups (61 and
      61%, respectively) than in the other groups (44% pT3a and 10% pT3c; p < 0.001).
      During the median follow-up period of 9 years (range, 2-38 years), recurrence
      occurred in 169 patients with T3 tumors (16%), including 18 with pT3a (6%), 100
      with pT3b (18%), 20 with pT3c (12%), and 31 with pT3d (48%). In a multivariate
      analysis, LN metastases (< 0.0001), extranodal extension (p = 0.03), FTC (vs.
      PTC) (p = 0.006), pT3b (p = 0.016), and pT3d (p = 0.047) were associated with an
      increased risk of recurrence. The 5-year RFS rates were 94.5, 82.2, 91.1, and
      50.3% for the pT3a, pT3b, pT3c, and pT3d groups, respectively (p < 0.01).
      CONCLUSION: Except for microcarcinoma, the risk of LN involvement is high and
      similar for the DTC patients with minimal ETE, regardless of the size of the
      tumor. The association of a tumor size of > 4 cm and ETE are associated with a
      poor prognosis and should justify the classification of these cases as a high
      risk group. Other pT3 patients with no LN metastases could be individualized as a
      low-risk group.

PMID- 29445866
TI  - Second primary colorectal cancer among endometrial cancer survivor: shared
      etiology and treatment sequelae.
AB  - PURPOSE: To evaluate the incidence of colon cancer as a second primary cancer
      (CCSPC) and the survival outcomes of women with and without CCSPC after the
      diagnosis of endometrial cancer (EC). METHODS: The standardized incidence ratio
      (SIR) of CCSPC and survival outcomes of EC survivors with and without CCSPC were
      analyzed using data from January 1 1993 to December 31 2011, obtained from the
      Korea Central Cancer Registry. RESULTS: Of 14,797 EC survivors, 147 (0.99%)
      developed CCSPC after an average interval of 5.5 years. The SIR of CCSPC among EC
      survivors was 2.56, higher than that of colon cancer in the general population.
      The SIR of CCSPC was highest for the ascending (3.77), followed by the transverse
      (3.45), descending colon (2.06), and rectum (1.99). The risk of a proximal site
      of CCSPC was high, especially within 5 years after the diagnosis of EC in the
      ascending (SIR, 4.37) and transverse (4.91) colon, and in young survivors (< 60
      years) in the ascending (5.19) and transverse (3.82) colon. The 5- and 10-year
      overall survival rates were 84.8 and 80.4% among survivors with EC only and 89.2
      and 76.3% for survivors with CCSPC, respectively. CONCLUSIONS: The risk of CCSPC
      among EC survivors increases especially in the proximal colon in young survivors.
      These results could be used for surveillance and counseling of EC survivors.

PMID- 29445867
TI  - Sustained effects of neurofeedback in ADHD: a systematic review and meta
      analysis.
AB  - Neurofeedback (NF) has gained increasing interest in the treatment of attention
      deficit/hyperactivity disorder (ADHD). Given learning principles underlie NF,
      lasting clinical treatment effects may be expected. This systematic review and
      meta-analysis addresses the sustainability of neurofeedback and control treatment
      effects by considering randomized controlled studies that conducted follow-up
      (FU; 2-12 months) assessments among children with ADHD. PubMed and Scopus
      databases were searched through November 2017. Within-group and between-group
      standardized mean differences (SMD) of parent behavior ratings were calculated
      and analyzed. Ten studies met inclusion criteria (NF: ten studies, N = 256;
      control: nine studies, N = 250). Within-group NF effects on inattention were of
      medium effect size (ES) (SMD = 0.64) at post-treatment and increased to a large
      ES (SMD = 0.80) at FU. Regarding hyperactivity/impulsivity, NF ES were medium at
      post-treatment (SMD = 0.50) and FU (SMD = 0.61). Non-active control conditions
      yielded a small significant ES on inattention at post-treatment (SMD = 0.28) but
      no significant ES at FU. Active treatments (mainly methylphenidate), had large ES
      for inattention (post: SMD = 1.08; FU: SMD = 1.06) and medium ES for
      hyperactivity/impulsivity (post: SMD = 0.74; FU: SMD = 0.67). Between-group
      analyses also revealed an advantage of NF over non-active controls [inattention
      (post: SMD = 0.38; FU: SMD = 0.57); hyperactivity-impulsivity (post: SMD = 0.25;
      FU: SMD = 0.39)], and favored active controls for inattention only at pre-post
      (SMD = - 0.44). Compared to non-active control treatments, NF appears to have
      more durable treatment effects, for at least 6 months following treatment. More
      studies are needed for a properly powered comparison of follow-up effects between
      NF and active treatments and to further control for non-specific effects.

PMID- 29445869
TI  - Guidelines for management of rheumatic diseases in developing countries from
      basics to real-world situation: relevance, need, and processes for development.
AB  - Guidelines or recommendations help to provide uniform standards in medical
      practice. The development of guidelines requires adherence to pre-defined norms
      prescribed by different international organizations such as the European League
      against Rheumatism (EULAR). We searched Pubmed and LILACS to identify published
      papers in five major rheumatic diseases (rheumatoid arthritis, systemic lupus
      erythematosus, spondyloarthropathies, osteoarthritis, and scleroderma) from
      different countries based on their economic prosperity and could find a lack of
      published literature from most economically weaker regions. Similarly, published
      guidelines in these rheumatic diseases were sparse from Asia and Africa, which
      are economically developed to a lesser extent than other regions of the world.
      Considering differing economic realities driving patient care in different
      regions of the world, unique challenges in certain geographic areas such as
      musculoskeletal manifestations of infectious diseases like leprosy and
      tuberculosis, as well as distinct risk of malignancies and other comorbid
      conditions, National Rheumatology societies should work towards developing more
      guidelines for rheumatic diseases from regions such as Asia and Africa, while
      following strictly the prescribed norms for the same. With a paucity of
      guidelines for such regions currently, an alternative (although less preferable)
      suggestion would be that major international societies, whose guidelines are
      widely read and followed the world over, should consider inputs from experts from
      diverse regions of the world while developing these guidelines.

PMID- 29445868
TI  - Induction of systemic resistance in tomato against Botrytis cinerea by N-decanoyl
      homoserine lactone via jasmonic acid signaling.
AB  - MAIN CONCLUSION: N-decanoyl-homoserine lactone activates plant systemic
      resistance against Botrytis cinerea in tomato plants, which is largely dependent
      on jasmonic acid biosynthesis and signal transduction pathways. Rhizosphere
      bacteria secrete N-acylated-homoserine lactones (AHLs), a type of specialized
      quorum-sensing signal molecule, to coordinate their population density during
      communication with their eukaryotic hosts. AHLs behave as low molecular weight
      ligands that are sensed by plants and promote the host's resistance against
      foliar pathogens. In this study, we report on N-decanoyl-homoserine lactone
      (DHL), which is a type of AHL that induces systemic immunity in tomato plants and
      protects the host organism against the necrotrophic fungus Botrytis cinerea. Upon
      DHL treatment, tomato endogenous jasmonic acid (JA) biosynthesis (rather than
      salicylic acid biosynthesis) and signal transduction were significantly
      activated. Strikingly, the DHL-induced systemic resistance against B. cinerea was
      blocked in the tomato JA biosynthesis mutant spr2 and JA signaling gene-silenced
      plants. Our findings highlight the role of DHL in systemic resistance against
      economically important necrotrophic pathogens and suggest that DHL-induced
      immunity against B. cinerea is largely dependent on the JA signaling pathway.
      Manipulation of DHL-induced resistance is an attractive disease management
      strategy that could potentially be used to enhance disease resistance in diverse
      plant species.

PMID- 29445870
TI  - Extralevator versus standard abdominoperineal excision in locally advanced rectal
      cancer: a retrospective study with long-term follow-up.
AB  - PURPOSE: To analyze the results of abdominoperineal excisions (APE) for locally
      advanced rectal cancer at our institution before and after the adoption of
      extralevator abdominoperineal excision (ELAPE) with a special reference to long
      term survival. METHODS: A retrospective cohort study conducted in a tertiary
      referral center. All consecutive patients operated for locally advanced (TNM
      classification T3-4) rectal cancer with APE in 2004-2009 were compared to
      patients with similar tumors operated with ELAPE in 2009-2016. RESULTS: Forty-two
      ELAPE and 27 APE patients were included. Circumferential resection margin (CRM)
      was less than 1 mm (R1-resection) in 10 (24%) of ELAPE patients and 11 (41%) of
      APE patients (p = 0.1358). Intraoperative perforation (IOP) occurred in 4 (10%)
      patients and 6 (22%) patients in ELAPE and APE groups, respectively (p = 0.1336).
      There were 3 (7%) local recurrences (LRs) in ELAPE group and 5 (19%) in APE (p =
      0.2473). There were no statistical differences in adverse events, overall
      survival, or disease-free survival between ELAPE and APE groups. CONCLUSIONS: We
      found a non-significant tendency to lower rates of IOP and positive CRM as well
      as lower rate of LR in the ELAPE group. Long-term survival and adverse events did
      not differ between the groups. ELAPE is beneficial for the surgeon in offering
      better vicinity to the perineal area and better work ergonomics. These technical
      aspects and the clinically very important tendency to lower rate of LR support
      the use of ELAPE technique in spite of the lack of survival benefit.

PMID- 29445871
TI  - Are we doing too much?: local excision before radical surgery in early rectal
      cancer.
AB  - PURPOSE: In early rectal cancer cases, the use of local excision is increasing.
      The general indication for local excision is based on the preoperative stage, but
      there is often a discrepancy between pre and postoperative stages. We sought to
      determine the indications for local excision in T1 rectal adenocarcinoma patients
      by comparing the preoperative clinical and postoperative pathological stages. A
      second aim was to compare the oncologic outcomes between local excision and
      radical resection. METHODS: Between 2004 and 2014, 152 T1 rectal adenocarcinoma
      patients were enrolled. We divided the subjects into two groups, local excision
      and radical resection, depending on the modality of treatment the patients
      initially received. The group of patients who underwent radical resection was
      subsequently subdivided into "excisable" and "non-excisable" groups based on the
      postoperative pathology. RESULTS: Of 152 patients, 28 patients (18.4%) underwent
      local excision, while 124 patients (81.6%) underwent radical resection. Of 124
      patients, in clinically suspected T2 or less and N0 (93) cases, 50 patients
      (53.8%) needed treatment beyond local excision, and local excision was sufficient
      for 43 patients (46.2%). The 3-year overall survival (p = 0.393) and 3-year
      disease-free survival (p = 0.076) between the local excision and radical
      resection groups showed no significant difference. CONCLUSIONS: The clinical T
      stage was overestimated in more than half of the cases. Therefore, if cT1/2
      tumors with cN0 are suspected preoperatively, local excision is initially
      recommended and will allow for determination of underlying pathology. The
      clinician can then decide whether to monitor or intervene with radical resection.

PMID- 29445872
TI  - Bowman layer transplantation: 5-year results.
AB  - PURPOSE: The purpose of this study was to evaluate the 5-year clinical results of
      isolated Bowman layer (BL) transplantation in the treatment of advanced
      keratoconus. METHODS: In this prospective, single-center, interventional case
      series at a tertiary referral center, 20 eyes of 17 patients with advanced
      keratoconus underwent BL transplantation, i.e. an isolated Bowman layer graft was
      positioned into a manually dissected mid-stromal pocket. Scheimpflug-based
      corneal tomography measurements, best corrected spectacle and contact lens visual
      acuities (BSCVA and BCLVA), endothelial cell density, and complications were
      evaluated up to 5 years after surgery. RESULTS: Measured simulated and maximum
      keratometry (Kmean and Kmax) values were stable up to 5 years after surgery (P =
      .310 and P = .195 for 5 years compared to 1 month follow-up, respectively),
      following an initial decrease from pre- to 1 month postoperatively (P < .001
      each). Mean LogMAR BSCVA remained stable (P > .99), after an initial improvement
      from pre- to 12 months postoperatively (P = .007). Mean BCLVA did not change from
      preoperative to 5 years postoperatively (P = .219). During all postoperative
      follow-ups, mean densitometry values were higher than preoperatively (P < .001).
      A corneal hydrops occurred in one eye at 4.5 years postoperatively; no other
      postoperative complications were observed. Kaplan-Meier analysis showed an
      estimated success rate of 84% at 5 years postoperatively. Endothelial cell
      density remained stable from before to 5 years after surgery (P = .319).
      CONCLUSIONS: After early postoperative corneal flattening, topographies were
      stable up to 5 years after BL transplantation, preserving BCLVA and contact lens
      tolerance, potentially allowing long term postponement of penetrating or deep
      anterior lamellar keratoplasty.

PMID- 29445873
TI  - Maturation of the [Ni-4Fe-4S] active site of carbon monoxide dehydrogenases.
AB  - Nickel-containing enzymes are diverse in terms of function and active site
      structure. In many cases, the biosynthesis of the active site depends on
      accessory proteins which transport and insert the Ni ion. We review and discuss
      the literature related to the maturation of carbon monoxide dehydrogenases (CODH)
      which bear a nickel-containing active site consisting of a [Ni-4Fe-4S] center
      called the C-cluster. The maturation of this center has been much less studied
      than that of other nickel-containing enzymes such as urease and NiFe hydrogenase.
      Several proteins present in certain CODH operons, including the nickel-binding
      proteins CooT and CooJ, still have unclear functions. We question the conception
      that the maturation of all CODH depends on the accessory protein CooC described
      as essential for nickel insertion into the active site. The available literature
      reveals biological variations in CODH active site biosynthesis.

PMID- 29445874
TI  - New evidence of predation on humans by cookiecutter sharks in Kauai, Hawaii.
AB  - The feeding patterns of species of large sharks on human corpses are well
      documented in the literature however, that of smaller sharks are less known. This
      may introduce uncertainty in the medicolegal conclusions. For that reason,
      accurate identification of patterns of shark predation is very relevant,
      specifically in areas bordered by the sea. In the case described here, an
      unidentified lesion was noted on the body of a victim of a scuba diving accident
      off the island of Kauai, in Hawaii. The aim of this study was to identify the
      origin of the lesion and investigate its potential to inform on the context of
      death and/or decomposition. The original outline of the lesion was digitally
      reconstructed to enable the collection of measurements which were compared with
      the literature and interpreted with an interdisciplinary approach. This approach
      permitted to determine that the macroscopic appearance and dimensions of the
      lesion (major axis = 3.53 cm) were consistent with a bitemark of a cookiecutter
      shark (Isistius brasiliensis). It was further determined that the bitemark was
      incomplete and that the specimen involved had a total length of about 24 cm and
      was likely to be a juvenile. This is the second report in the published
      literature of cookiecutter bitemarks on humans in the Hawaiian waters. This study
      brings new evidence-based insights into the interactions between cookiecutter
      sharks and human remains in marine environments and provides a valuable
      contribution to the knowledge base on the topic.

PMID- 29445875
TI  - Interference screw insertion angle has no effect on graft fixation strength for
      insertional Achilles tendon reconstruction.
AB  - PURPOSE: To compare the effect of two interference screw insertion angles on the
      biomechanical properties of the insertional Achilles tendon (IAT) reconstruction.
      METHODS: Nine matched pairs of fresh-frozen human cadaveric Achilles tendon
      specimens were randomized to two groups with interference screw insertion angles
      of 60 degrees  and 120 degrees . The IAT reconstruction was performed by fixing
      the graft tendon with the interference screw. Each specimen was loaded to
      failure. The load at failure, stiffness, and mode of failure were documented.
      Differences in load at failure and stiffness were analysed. RESULTS: There was no
      statistically significant difference between the 60 degrees  and 120 degrees 
      groups for failure load (149.137 +/- 20.836 versus 155.428 +/- 28.343 N,
      respectively, n.s.) and stiffness (14.523 +/- 2.824 N/mm versus 14.727 +/- 2.192
      N/mm, respectively, n.s.). The most common mode of failure was the graft pulling
      out of the bone tunnel when the screw broke. CONCLUSIONS: Graft fixation at two
      different interference screw insertion angles for IAT reconstruction exhibited
      equivalent biomechanical performance. When performing this procedure, surgeons
      may choose the interference screw insertion angle based on personal preference.

PMID- 29445876
TI  - Toxicity of PEG-Coated CoFe2O4 Nanoparticles with Treatment Effect of Curcumin.
AB  - In this work, CoFe2O4 nanoparticles coated with polyethylene glycol (PEG) were
      successfully synthesized via a hydrothermal technique. Morphological studies of
      the samples confirmed the formation of polycrystalline pure-phase PEG-CoFe2O4
      nanoparticles with sizes of about 24 nm. Toxicity induced by CoFe2O4
      nanoparticles was investigated, and biological assays were performed to check the
      toxicity effects of CoFe2O4 nanoparticles. Moreover, the healing effect of
      toxicity induced in living organisms was studied using curcumin and it was found
      that biochemical indexes detoxified and improved to reach its normal level after
      curcumin administration. Thus, PEG-coated CoFe2O4 synthesized through a
      hydrothermal method can be utilized in biomedical applications and curcumin,
      which is a natural chemical with no side effects, can be used for the treatment
      of toxicity induced by the nanoparticles in living organisms.

PMID- 29445877
TI  - Sodium lactate improves renal microvascular thrombosis compared to sodium
      bicarbonate and 0.9% NaCl in a porcine model of endotoxic shock: an experimental
      randomized open label controlled study.
AB  - BACKGROUND: Sodium lactate seemed to improve fluid balance and avoid fluid
      overload. The objective of this study was to determine if these beneficial
      effects can be at least partly explained by an improvement in disseminated
      intravascular coagulation (DIC)-associated renal microvascular thrombosis.
      METHODS: Ancillary work of an interventional randomized open label controlled
      experimental study. Fifteen female "Large White" pigs (2 months old) were
      challenged with intravenous infusion of E. coli endotoxin. Three groups of five
      animals were randomly assigned to receive different fluids: a treatment group
      received sodium lactate 11.2% (SL group); an isotonic control group received 0.9%
      NaCl (NC group); a hypertonic control group, with the same amount of osmoles and
      sodium than SL group, received sodium bicarbonate 8.4% (SB group). Glomerular
      filtration rate (GFR) markers, coagulation and inflammation parameters were
      measured over a 5-h period. Immediately after euthanasia, kidneys were withdrawn
      for histological study. Statistical analysis was performed with nonparametric
      tests and the Dunn correction for multiple comparisons. A p < 0.05 was considered
      significant. RESULTS: The direct immunofluorescence study revealed that the
      percentage of capillary sections thrombosed in glomerulus were significantly
      lesser in SL group [5 (0-28) %] compared to NC [64 (43-79) %, p = 0.01] and SB
      [64 (43-79), p = 0.03] groups. Alterations in platelet count and fibrinogen level
      occurred earlier and were significantly more pronounced in both control groups
      compared to SL group (p < 0.05 at 210 and 300 min). The increase in thrombin
      antithrombin complexes was significantly higher in NC [754 (367-945) MUg/mL; p =
      0.03] and SB [463 (249-592) MUg/mL; p = 0.03] groups than in SL group [176 (37
      265) MUg/mL]. At the end of the experiment, creatinine clearance was
      significantly higher in SL group [55.46 (30.07-67.85) mL/min] compared to NC
      group [1.52 (0.17-27.67) mL/min, p = 0.03]. CONCLUSIONS: In this study, we report
      that sodium lactate improves DIC-associated renal microvascular thrombosis and
      preserves GFR. These findings could at least partly explain the better fluid
      balance observed with sodium lactate infusion.

PMID- 29445878
TI  - Feasibility of intraoperative detection of sentinel lymph nodes with 89-zirconium
      labelled nanocolloidal albumin PET-CT and a handheld high-energy gamma probe.
AB  - BACKGROUND: PET/CT lymphoscintigraphy using 89Zr-nanocolloidal albumin has the
      potential to improve the preoperative identification of sentinel lymph nodes
      (SLNs), especially if located in the near proximity of the primary tumour. This
      study aims to demonstrate the feasibility of PET/CT lymphoscintigraphy followed
      by intraoperative detection of 89Zr-nanocolloidal albumin containing SLNs with
      the use of a handheld high-energy gamma probe. METHODS: PET/CT lymphoscintigraphy
      was performed after peritumoural injection of 89Zr-nanocolloidal albumin in five
      patients with oral cavity carcinoma planned for surgical resection. SLN biopsy
      procedure was performed 18 h later. SLNs were detected using detailed information
      of PET/CT and the high-energy gamma probe. RESULTS: In all patients, SLNs were
      identified on PET/CT lymphoscintigraphy. Intraoperative detection using the high
      energy gamma probe was possible in 10 of 13 SLNs, at a short distance from the
      SLN. CONCLUSIONS: This study demonstrates that intraoperative detection of SLNs
      containing 89Zr-nanocolloidal albumin using a handheld high-energy gamma probe is
      feasible, but its clinical use and sensitivity seem to be limited. TRIAL
      REGISTRATION: CCMO NL37222.092.11.

PMID- 29445879
TI  - Role of Thioredoxin in Age-Related Hypertension.
AB  - PURPOSE OF REVIEW: Although the roles of oxidant stress and redox perturbations
      in hypertension have been the subject of several reviews, role of thioredoxin
      (Trx), a major cellular redox protein in age-related hypertension remains
      inadequately reviewed. The purpose of this review is to bring readers up-to-date
      with current understanding of the role of thioredoxin in age-related
      hypertension. RECENT FINDINGS: Age-related hypertension is a major underlying
      cause of several cardiovascular disorders, and therefore, intensive management of
      blood pressure is indicated in most patients with cardiovascular complications.
      Recent studies have shown that age-related hypertension was reversed and remained
      lowered for a prolonged period in mice with higher levels of human Trx (Trx-Tg).
      Additionally, injection of human recombinant Trx (rhTrx) decreased hypertension
      in aged wild-type mice that lasted for several days. Both Trx-Tg and aged wild
      type mice injected with rhTrx were normotensive, showed increased NO production,
      decreased arterial stiffness, and increased vascular relaxation. These studies
      suggest that rhTrx could potentially be a therapeutic molecule to reverse age
      related hypertension in humans. The reversal of age-related hypertension by
      restoring proteins that have undergone age-related modification is conceptually
      novel in the treatment of hypertension. Trx reverses age-related hypertension via
      maintaining vascular redox homeostasis, regenerating critical vasoregulatory
      proteins oxidized due to advancing age, and restoring native function of proteins
      that have undergone age-related modifications with loss-of function. Recent
      studies demonstrate that Trx is a promising molecule that may ameliorate or
      reverse age-related hypertension in older adults.

PMID- 29445881
TI  - Study of salivary and serum vaspin and total antioxidants in anorexia nervosa.
AB  - OBJECTIVES: Patients with anorexia nervosa (AN) are primarily at high risk of
      multiple somatic complications, including oral diseases. In recent years, a
      number of new molecules that may play a potentially important role in AN progress
      and prognosis have been identified in saliva, but their exact roles are still
      poorly understood. Two such group of substances are antioxidants and vaspin. The
      purpose of this observational, cross-sectional study was to measure both the
      salivary and serum total antioxidant status (TAS), and vaspin (VASP)
      concentrations of patients with AN in comparison to an average population.
      MATERIAL AND METHODS: Ninety subjects participated (30 patients with AN, 60
      matched healthy control subjects). A clinical examination was made, and blood and
      salivary samples were taken during the acute stage of AN (BMI < 15 kg/m2) in the
      first week of hospitalization. Enzyme immunoassay (ELISA) suitable for measuring
      VASP and colorimetric assay for TAS were used. RESULTS: Anorexic patients had
      significant reductions in salivary flow, TAS, and an elevation in VASP levels in
      their saliva and serum. Significant correlations between TAS, VASP, salivary
      flow, and nutritional status were detected. CONCLUSION: Determination of TAS and
      VASP in combined biological material confirmed that saliva might be a reliable
      non-invasive source of information for potent nutritional biomarkers. CLINICAL
      RELEVANCE: Our findings suggest that VASP cannot be excluded, as its increased
      concentration in saliva is an adaptive mechanism in reduced TAS, one resulting
      from diminished salivary secretion. It is therefore worth conducting further
      research aimed at recognizing the role of TAS and VASP in the saliva of
      underweight patients.

PMID- 29445882
TI  - Procedure rates performed by emergency medicine residents: a retrospective
      review.
AB  - BACKGROUND: The purpose of our study is to investigate rates of individual
      procedures performed by residents in our emergency medicine (EM) residency
      program. Different programs expose residents to different training environments.
      Our hypothesis is that ultrasound examinations are the most commonly performed
      procedure in our residency. METHODS: The study took place in an academic level I
      trauma center with multiple residency and fellowship programs including surgery,
      surgical critical care, trauma, medicine, pulmonary/critical care, anesthesiology
      and others. Also, the hospital provides a large emergency medical services
      program providing basic and advanced life support and critical care transport,
      which is capable of performing rapid sequence intubation. Each EM residency
      class, except for the first 2 months of the inaugural class, used New Innovations
      to log procedures. New Innovations is an online database for tracking residency
      requirements, such as procedures and hours. For the first 3 months, procedures
      were logged by hand on a log sheet. In addition, our department has a wireless
      electronic system (Qpath) for recording and logging ultrasound images. These logs
      were reviewed retrospectively without any patient identifiers. Actual procedures
      and simulation procedures were combined for analysis as they were only logged
      separately halfway through the study period. Procedures were summed and the
      average procedure rate per resident per year was calculated. RESULTS: In total,
      66 full resident years were analyzed. Overall, ultrasound was the most commonly
      performed procedure, with each resident performing 125 ultrasounds per year.
      Removing "resuscitations," the second most common was endotracheal intubation,
      performed 28.91 times per year, and third most was laceration repair, which was
      performed 17.39 times per year. Our lowest performed procedure was thoracentesis,
      which was performed on average 0.11 times per resident per year. CONCLUSIONS:
      Residents performed a variety of procedures each year. Ultrasound examinations
      were the most frequent procedure performed. The number of ultrasound procedures
      performed may reflect the changing training landscape and influence future
      Accreditation Council of Graduate Medical Education requirements.

PMID- 29445880
TI  - The headache under-response to treatment (HURT) questionnaire, an outcome measure
      to guide follow-up in primary care: development, psychometric evaluation and
      assessment of utility.
AB  - BACKGROUND: Headache disorders are both common and burdensome but, given the many
      people affected, provision of health care to all is challenging. Structured
      headache services based in primary care are the most efficient, equitable and
      cost-effective solution but place responsibility for managing most patients on
      health-care providers with limited training in headache care. The development of
      practical management aids for primary care is therefore a purpose of the Global
      Campaign against Headache. This manuscript presents an outcome measure, the
      Headache Under-Response to Treatment (HURT) questionnaire, describing its
      purpose, development, psychometric evaluation and assessment for clinical
      utility. The objective was a simple-to-use instrument that would both assess
      outcome and provide guidance to improving outcome, having utility across the
      range of headache disorders, across clinical settings and across countries and
      cultures. METHODS: After literature review, an expert consensus group drawn from
      all six world regions formulated HURT through item development and item reduction
      using item-response theory. Using the American Migraine Prevalence and Prevention
      Study's general-population respondent panel, two mailed surveys assessed the
      psychometric properties of HURT, comparing it with other instruments as external
      validators. Reliability was assessed in patients in two culturally-contrasting
      clinical settings: headache specialist centres in Europe (n = 159) and primary
      care centres in Saudi Arabia (n = 40). Clinical utility was assessed in similar
      settings (Europe n = 201; Saudi Arabia n = 342). RESULTS: The final instrument,
      an 8-item self-administered questionnaire, addressed headache frequency,
      disability, medication use and effect, patients' perceptions of headache
      "control" and their understanding of their diagnoses. Psychometric evaluation
      revealed a two-factor model (headache frequency, disability and medication use;
      and medication efficacy and headache control), with scale properties apparently
      stable across disorders and correlating well and in the expected directions with
      external validators. The literature review found few instruments linking
      assessment to clinical advice or suggested actions: HURT appeared to fill this
      gap. In European specialist care, it showed utility as an outcome measure across
      headache disorders. In Saudi Arabian primary care, HURT (translated into Arabic)
      was reliable and responsive to clinical change. CONCLUSIONS: With demonstrated
      validity and clinical utility across disorders, cultures and settings, HURT is
      available for clinical and research purposes.

PMID- 29445883
TI  - Neurological Complications of Acute and Chronic Otitis Media.
AB  - PURPOSE OF REVIEW: The aim of this study is to discuss the symptoms, diagnosis,
      and management of the neurologic complications of acute and chronic otitis media.
      RECENT FINDINGS: Antibiotic therapy has greatly reduced the frequency of
      complications of otitis media. However, it is of vital importance to remain aware
      of the possible development of neurologic complications. There is a trend toward
      less severe presenting symptoms including otorrhea, headache, nausea, and fever,
      with altered mental status and focal neurologic deficits presenting later. In
      order to reduce morbidity, early deployment of a multidisciplinary approach with
      prompt imaging and laboratory studies is imperative to guide appropriate
      management. Complications of acute and chronic otitis media may present with
      neurologic signs and symptoms. It is important to recognize the possible otitic
      origin of such complications to ensure proper management and to decrease overall
      morbidity and mortality.

PMID- 29445884
TI  - Acute kidney injury epidemiology, risk factors, and outcomes in critically ill
      patients 16-25 years of age treated in an adult intensive care unit.
AB  - BACKGROUND: Most studies of acute kidney injury (AKI) have focused on older
      adults, and little is known about AKI in young adults (16-25 years) that are
      cared for in an adult intensive care unit (ICU). We analyzed data from a large
      single-center ICU database and defined AKI using the Kidney Disease Improving
      Global Outcomes criteria. We stratified patients 16-55 years of age into four age
      groups for comparison and used multivariable logistic regression to identify
      associations of potential susceptibilities and exposures with AKI and mortality.
      RESULTS: AKI developed in 52.6% (n = 8270) of the entire cohort and in 39.8% of
      the young adult age group (16-25 years). The AUCs for the age categories were
      similar at 0.754, 0.769, 0.772, and 0.770 for the 16-25-, 26-35-, 36-45-, and 45
      55-year age groups, respectively. For the youngest age group, diabetes (OR 1.89;
      95% CI 1.09-3.29), surgical reason for admission (OR 1.79; 95% CI 1.44-2.23),
      severity of illness (OR 1.02; 95% CI 1.02-1.03), hypotension (OR 1.13; 95% CI
      1.04-1.24), and certain medications (vancomycin and calcineurin inhibitors) were
      all independently associated with AKI. AKI was a significant predictor for longer
      length of stay, ICU mortality, and mortality after discharge. CONCLUSIONS: AKI is
      a common event for young adults admitted to an adult tertiary care center ICU
      with an associated increased length of stay and risk of mortality. Potentially
      modifiable risk factors for AKI including medications were identified for all
      stratified age groups.

PMID- 29445886
TI  - Infinite dilution activity coefficient from SMD calculations: accuracy and
      performance for predicting liquid-liquid equilibria.
AB  - Prediction of liquid-liquid phase equilibria is an important goal in the physical
      chemistry of solutions. Quantum chemistry methods, combined with a dielectric
      continuum description of the solvent, has received attention as a first principle
      approach. In this work, the performance of the continuum solvation model based on
      density (SMD) for prediction of gammainfinity in binary liquid mixtures, using 46
      values of gammainfinity, was evaluated. We found the mean uncertainty of RTln
      gammainfinity to be 0.92 kcal mol-1. Based on the calculated gammainfinity and
      the two parameters of the Redlich-Kister expansion, we calculated the liquid
      liquid phase equilibria. Based on 26 values of solubility, an uncertainty of 0.66
      was found in the logarithm of molar fraction of the smallest component in each
      phase. Our results suggest this approach can be used for fast and semi
      quantitative prediction of phase behavior. More reliable predictions could be
      obtained with improvements in the SMD model. Graphical abstract Prediction of
      liquid-liquid phase equilibria?.

PMID- 29445885
TI  - The Interplay of Lipids, Lipoproteins, and Immunity in Atherosclerosis.
AB  - PURPOSE OF REVIEW: Atherosclerosis is an inflammatory disorder of the arterial
      wall, in which several players contribute to the onset and progression of the
      disease. Besides the well-established role of lipids, specifically cholesterol,
      and immune cell activation, new insights on the molecular mechanisms underlying
      the atherogenic process have emerged. RECENT FINDINGS: Meta-inflammation, a
      condition of low-grade immune response caused by metabolic dysregulation,
      immunological memory of innate immune cells (referred to as "trained immunity"),
      cholesterol homeostasis in dendritic cells, and immunometabolism, i.e., the
      interplay between immunological and metabolic processes, have all emerged as new
      actors during atherogenesis. These observations reinforced the interest in
      directly targeting inflammation to reduce cardiovascular disease. The novel
      acquisitions in pathophysiology of atherosclerosis reinforce the tight link
      between lipids, inflammation, and immune response, and support the benefit of
      targeting LDL-C as well as inflammation to decrease the CVD burden. How this will
      translate into the clinic will depend on the balance between costs (monoclonal
      antibodies either to PCSK9 or to IL-1beta), side effects (increased incidence of
      death due to infections for anti-IL-1beta antibody), and the benefits for
      patients at high CVD risk.

PMID- 29445887
TI  - Lung volumes and lung volume recruitment in ARDS: a comparison between supine and
      prone position.
AB  - BACKGROUND: The use of positive end-expiratory pressure (PEEP) and prone position
      (PP) is common in the management of severe acute respiratory distress syndrome
      patients (ARDS). We conducted this study to analyze the variation in lung volumes
      and PEEP-induced lung volume recruitment with the change from supine position
      (SP) to PP in ARDS patients. METHODS: The investigation was conducted in a
      multidisciplinary intensive care unit. Patients who met the clinical criteria of
      the Berlin definition for ARDS were included. The responsible physician set basal
      PEEP. To avoid hypoxemia, FiO2 was increased to 0.8 1 h before starting the
      protocol. End-expiratory lung volume (EELV) and functional residual capacity
      (FRC) were measured using the nitrogen washout/washin technique. After the
      procedures in SP, the patients were turned to PP and 1 h later the same
      procedures were made in PP. RESULTS: Twenty-three patients were included in the
      study, and twenty were analyzed. The change from SP to PP significantly increased
      FRC (from 965 +/- 397 to 1140 +/- 490 ml, p = 0.008) and EELV (from 1566 +/- 476
      to 1832 +/- 719 ml, p = 0.008), but PEEP-induced lung volume recruitment did not
      significantly change (269 +/- 186 ml in SP to 324 +/- 188 ml in PP, p = 0.263).
      Dynamic strain at PEEP decreased with the change from SP to PP (0.38 +/- 0.14 to
      0.33 +/- 0.13, p = 0.040). CONCLUSIONS: As compared to supine, prone position
      increases resting lung volumes and decreases dynamic lung strain.

PMID- 29445888
TI  - Addressing Molecular Diagnosis of Occupational Allergies.
AB  - PURPOSE OF REVIEW: Numerous clinically relevant allergenic molecules enhance the
      performance of specific (s) IgE tests and improve the specificity of allergy
      diagnosis. This review aimed to summarize our current knowledge of the high
      molecular-weight allergens involved in the development of occupational asthma and
      rhinitis and to critically analyze the contribution of component-resolved
      diagnosis in the management of these conditions. RECENT FINDINGS: There is a lack
      of standardization and validation for most available extracts of occupational
      agents, and assessment of sIgE reactivity to occupational allergen components has
      been poorly investigated, with the notable exception of natural rubber latex
      (NRL) and wheat flour. In the case of NRL, the application of recombinant single
      allergens and amplification of natural extracts with stable recombinant allergens
      improved the test sensitivity. IgE-sensitization profile in patients with baker's
      asthma showed great interindividual variation, and extract-based diagnostic is
      still recommended. For other occupational allergens, it remains necessary to
      evaluate the relevance of single allergen molecules for the sensitization induced
      by occupational exposure. Progress has been made to characterize occupational
      allergens especially NRL and wheat, although there is still an unmet need to
      increase the knowledge of occupational allergens, to include standardized tools
      into routine diagnostic, and to evaluate their usefulness in clinical practice.

PMID- 29445889
TI  - Clinical significance of circulating tumor cells from lung cancer patients using
      microfluidic chip.
AB  - Circulating tumor cells (CTCs) exist in the peripheral blood and have an
      important role in the disease development, tumor metastasis and clinical
      surveillance, especially in the process of metastasis. However, the technology of
      detecting CTCs still had a large challenge since they were rare in the peripheral
      blood. Here, we developed a size-based microfluidic chip, which contained array
      and filter channel array that could enrich CTCs from blood samples more quickly
      and conveniently. Combined with clinical specimen, we analyzed CTCs in 200 lung
      cancer patients by this microfluidic chip. The microfluidic device has high
      specificity and sensitivity in detecting CTCs (86.0% sensitivity and 98%
      specificity). Furthermore, the number of CTCs showed a increasing trend according
      to the stage of the disease (the mean number of I stage 5.0 +/- 5.121 versus II
      stage 8.731 +/- 6.36 versus III stage 16.81 +/- 9.556 versus IV stage 28.72 +/-
      17.39 cells/mL, P < 0.05). The number of CTCs was concurrent with the condition
      of pathological type and metastasis patients. Compared to conventional markers
      like CEA, CY211, SCC, CTCs showed a higher positive rate in diagnosed patients.
      The advanced microfluidic device could capture tumor cells without reliance on
      cell surface expression markers and provide a fast, convenient, economical method
      in detecting CTCs, thereby offering potential to design effective and
      individualized cancer therapies.

PMID- 29445890
TI  - Benign endometrial proliferations mimicking malignancies: a review of problematic
      entities in small biopsy specimens.
AB  - Benign proliferations that mimic malignancies are commonly encountered during the
      course of assessment of small and fragmented endometrial samples. Although
      benign, endometrial epithelial metaplasias often coexist with premalignant or
      malignant lesions causing diagnostic confusion. The difficulty with mucinous
      metaplasia lies in its distinction from atypical mucinous glandular
      proliferations and mucinous carcinomas, which are associated with significant
      interobserver variability. Papillary proliferation of the endometrium is commonly
      associated with hormonal drugs and endometrial polyps and is characterised by
      papillae with fibrovascular cores covered by epithelial cells without cytologic
      atypia. They are classified into simple or complex papillary proliferations
      depending on the architectural complexity and extent of proliferation. Complex
      papillary proliferations are associated with a high risk of concurrent or
      subsequent hyperplasia with atypia/carcinoma. Papillary proliferations may have
      coexisting epithelial metaplasias and, most commonly, mucinous metaplasia and
      syncytial papillary change. Those with striking mucinous metaplasia overlap
      morphologically with papillary mucinous metaplasia. The latter has been proposed
      as a precursor of endometrial mucinous carcinoma. Misinterpreting the Arias
      Stella reaction as a malignant or premalignant lesion is more likely to occur if
      the pathologist is unaware that the patient is pregnant or on hormonal drugs.
      Endometrial hyperplasia with secretory changes may occasionally be difficult to
      distinguish from the torturous and crowded glands of a late secretory
      endometrium. Endometrial polyps may have abnormal features that can be
      misinterpreted as endometrial hyperplasia or Mullerian adenosarcoma. Awareness of
      these benign endometrial proliferations and their common association with
      hormonal medication or altered endogenous hormonal levels will help prevent the
      over-diagnosis of premalignant and malignant lesions.

PMID- 29445892
TI  - Performance evaluation of nonhomogeneous hospitals: the case of Hong Kong
      hospitals.
AB  - Throughout the world, hospitals are under increasing pressure to become more
      efficient. Efficiency analysis tools can play a role in giving policymakers
      insight into which units are less efficient and why. Many researchers have
      studied efficiencies of hospitals using data envelopment analysis (DEA) as an
      efficiency analysis tool. However, in the existing literature on DEA-based
      performance evaluation, a standard assumption of the constant returns to scale
      (CRS) or the variable returns to scale (VRS) DEA models is that decision-making
      units (DMUs) use a similar mix of inputs to produce a similar set of outputs. In
      fact, hospitals with different primary goals supply different services and
      provide different outputs. That is, hospitals are nonhomogeneous and the standard
      assumption of the DEA model is not applicable to the performance evaluation of
      nonhomogeneous hospitals. This paper considers the nonhomogeneity among hospitals
      in the performance evaluation and takes hospitals in Hong Kong as a case study.
      An extension of Cook et al. (2013) [1] based on the VRS assumption is developed
      to evaluated nonhomogeneous hospitals' efficiencies since inputs of hospitals
      vary greatly. Following the philosophy of Cook et al. (2013) [1], hospitals are
      divided into homogeneous groups and the product process of each hospital is
      divided into subunits. The performance of hospitals is measured on the basis of
      subunits. The proposed approach can be applied to measure the performance of
      other nonhomogeneous entities that exhibit variable return to scale.

PMID- 29445891
TI  - Immunohistochemical analysis and prognostic significance of PD-L1, PD-1, and CD8+
      tumor-infiltrating lymphocytes in Ewing's sarcoma family of tumors (ESFT).
AB  - Ewing's sarcoma family of tumors (ESFT) are aggressive neoplasms with scant tumor
      infiltrating lymphocytes. We analyzed the immunohistochemical (IHC) expression of
      PD-L1 and PD-1 and their prognostic significance in clinically localized
      neoplasms in a cohort of 370 ESFT. Slides prepared from tissue microarrays were
      stained for PD-L1, PD-1, and CD8. Membranous/cytoplasmic staining over 5% of
      tumor cells was regarded as positive for PD-L1 and PD-1. Prognostic analysis was
      done considering only clinically localized tumors (n = 217). PD-L1 expression was
      present in 19% of ESFT, while PD-1 was expressed in 26%. Forty-eight percent of
      tumors were negative and 12% were positive for both PD-L1 and PD-1. Metastatic
      tumors displayed higher expression of PD-L1 (p < 0.0001). Histological subtypes
      were not correlated with PD-L1 or PD-1 positivity. ESFT with elevated
      proliferation index (Ki-67) were associated with higher PD-L1 expression (p =
      0.049). Regarding prognosis, no significant association was found between PD-L1
      expression and progression-free survival (PFS) or overall survival (OS), whereas
      lack of PD-1 expression in tumor cells was correlated with both poor PFS (p =
      0.02) and poor OS (p = 0.004). Tumor-infiltrating CD8(+) T lymphocytes were
      observed in 15.4% of ESFT with informative results (347 tumors). No correlation
      was found between tumor-infiltrating CD8(+) T lymphocytes and ESFT histological
      subtypes, tumor location, or PD-1 and PD-L1 expression, nor with PFS (p = 0.473)
      or OS (p = 0.087). PD-L1 expression was not significantly related to prognosis.
      PD-1 was expressed in 26% of ESFT tumor cells and may have prognostic and
      therapeutic implications. CD8 expression in tumor-infiltrating lymphocytes was
      not related to prognosis.

PMID- 29445893
TI  - Nestin expression is differently regulated between odontoblasts and the
      subodontoblastic layer in mice.
AB  - The Nestin gene encodes type VI intermediate filament and is known to be
      expressed in undifferentiated cells during neurogenesis and myogenesis. To
      regulate Nestin expression, the first or second intron enhancer is activated in a
      tissue-dependent manner, for example, the former in mesodermal cells and the
      latter in neural stem cells. Although Nestin has also been used as a
      differentiation marker for odontoblasts during tooth development, how Nestin
      expression is regulated in odontoblasts remains unclear. Therefore, this study
      aimed to compare the expression patterns of Nestin-GFP (green fluorescent
      protein) with that of endogenous Nestin in developing teeth of Nestin-EGFP
      (enhanced GFP) transgenic mice, in which the second intron enhancer is connected
      with the EGFP domain, at postnatal 7d, 3w, and 8w. Immunohistochemical and in
      situ hybridization analyses revealed that endogenous Nestin protein and Nestin
      mRNA were intensely expressed in differentiated odontoblasts, while GFP
      immunoreactivity, which reflects the activity of Nestin second intron enhancer
      mediated transcription, was mainly observed in the subodontoblastic layer. These
      results indicate that the first intron enhancer may be activated in
      differentiated odontoblasts. Intriguingly, Nestin-GFP expression in the
      subodontoblastic layer was found to be restricted to the coronal pulp of molars,
      which is susceptible to tooth injuries. Because the subodontoblastic layer serves
      as a reservoir of newly differentiated odontoblast-like cells upon exogenous
      stimuli to dentin, our findings suggest that the original odontoblasts and
      regenerated odontoblast-like cells may differently regulate Nestin expression.

PMID- 29445894
TI  - Sparse QSAR modelling methods for therapeutic and regenerative medicine.
AB  - The quantitative structure-activity relationships method was popularized by
      Hansch and Fujita over 50 years ago. The usefulness of the method for drug design
      and development has been shown in the intervening years. As it was developed
      initially to elucidate which molecular properties modulated the relative potency
      of putative agrochemicals, and at a time when computing resources were scarce,
      there is much scope for applying modern mathematical methods to improve the QSAR
      method and to extending the general concept to the discovery and optimization of
      bioactive molecules and materials more broadly. I describe research over the past
      two decades where we have rebuilt the unit operations of the QSAR method using
      improved mathematical techniques, and have applied this valuable platform
      technology to new important areas of research and industry such as nanoscience,
      omics technologies, advanced materials, and regenerative medicine. This paper was
      presented as the 2017 ACS Herman Skolnik lecture.

PMID- 29445895
TI  - On reprogramming of tumor cells metabolism: detection of glycogen in the cell
      lines of hepatocellular origin with various degrees of dedifferentiation.
AB  - The reprogramming of cancer cells includes shifts in glucose and glycogen
      metabolism. The aim of our work was to check the ability of forming glycogen
      grains in hepatocellular tumor cell lines of various dedifferentiation levels. We
      studied the monolayer culture established in vitro after explanting cells from
      rat ascites Zajdela hepatoma strain C (ZH-C) as a "parental" line and its five
      daughter clonal sublines: the holoclonal sublines 3H, 5F, 6H and the meroclonal
      ones 1E, 9C, which possess, respectively, the properties of cancer stem-like
      cells (CSLCs) and cancer progenitor-like cells (CPLCs). Besides, we studied four
      permanent cell lines of a rat hepatoma HTC, two murine hepatomas BWTG3 and MH
      22a, and human hepatoblastoma HepG2. We used normal rat hepatocytes as positive
      control cells that form glycogen. We estimated relative cell dedifferentiation
      levels of the studied lines via analysis of cell morphology, morphometry and
      motility character on stained cell preparations and lifetime video files.
      Glycogen in the cells was detected using a Schiff type Au-SO2 reagent. All
      studied hepatocellular tumor lines were not of equal dedifferentiation level as
      manifested by different nucleus-to-cytoplasm ratio, by epithelium-like or
      fibroblast-like morphology, by tight or loosen intercellular contacts, by cell
      migration of collective or individual types. Glycogen fluorescence of uneven
      intensity was observed in all normal rat hepatocytes, but only in some cell
      groups or in single cells of hepatocellular tumor lines. The large or small
      fluorescent grains were found not only in relatively less dedifferentiated
      parental ZH-C line, BWTG3 and HepG2 lines, but also in moderately
      dedifferentiated 1E and HTC lines and even in severely dedifferentiated 3H, 5F
      and 6H sublines, as well as in the islets of the rat ascites hepatoma induced in
      vivo by the injection of 3H cells (the tumor-initiating cells). On the other
      hand, MH-22 and 9C lines, being relatively less and moderately dedifferentiated,
      showed no glycogen fluorescence. Thus, in 10 tumor cell lines of hepatocellular
      origin, an ability to reserve glycogen manifested no obvious dependency on their
      dedifferentiation level. Glycogen grains were detected in some cells even of the
      severely dedifferentiated lines: in single CSLCs of holoclonal ZH sublines grown
      in vitro and in a majority of tumor-initiating cells derived from ascites
      hepatoma in vivo. We suggest that dynamic changes in glycogen formation in CSLCs
      and tumor-initiating cells might be of importance for their dedifferentiation,
      self-renewal in vitro, survival and metastasis in vivo. The role of glycogen in
      maintaining viability and metastasis of tumor cells is to be further studied.

PMID- 29445896
TI  - GLP-1 Receptor Agonists and Cardiovascular Disease: a Meta-Analysis of Recent
      Cardiac Outcome Trials.
AB  - PURPOSE: The aim of this study is to examine the cardioprotective properties of
      Glucagon-like peptide-1 receptor agonist, a class of antihyperglycemic therapy,
      via meta-analysis of four recently published cardiovascular outcomes trials.
      METHODS: Meta-analysis was performed pooling data from the ELIXA, LEADER, SUSTAIN
      6 and EXSCEL trials. A random effects model was used to generate risk ratio with
      95% confidence interval for cardiovascular and safety outcomes. RESULTS: A total
      of 33,457 patients were included in the meta-analysis. Based on the study, GLP-1R
      agonists significantly reduced all-cause mortality (RR 0.89; 95% CI 0.82 to 0.96)
      and cardiovascular mortality (RR 0.88; 95% CI 0.80 to 0.97) when compared to
      placebo. When long-acting agents were analyzed alone, reduction in major adverse
      cardiac events (RR 0.88; 95% CI 0.81 to 0.97) and non-fatal strokes (RR 0.87; 95%
      CI 0.76 to 0.99) also showed significance. CONCLUSION: Overall, GLP-1R agonists
      appear to have cardioprotective properties likely via modification of metabolic
      parameters such as glycemic control, weight loss, and improvement in blood
      pressure. Additional studies are warranted to compare cardiovascular outcomes
      among the different agents.

PMID- 29445897
TI  - BrdU/EdU dual labeling to determine the cell-cycle dynamics of defined cellular
      subpopulations.
AB  - Measuring the mean duration of synthesis-phase (Ts) and of the total cell-cycle
      (Tc) within progenitor cell populations can provide important insights into the
      biology governing these cells. Rather than a passive process that shows little
      variability across cellular contexts, the cell-cycle is instead highly regulated.
      For example, in the rodent forebrain, Ts is selectively lengthened in radial
      glial progenitor cells undergoing symmetric versus asymmetric division. This
      lengthening is thought to minimize the potential for copying errors that can
      occur during DNA replication. Manipulating cell-cycle duration can also affect
      cell fate, demonstrating that in certain circumstances cell-cycle duration is an
      instructive process. Currently, cell-cycle length is typically measured using
      either cumulative labeling with a single thymidine analogue, or via dual
      thymidine analogue labeling approaches. However, these methods are often time
      consuming and inefficient. Here, using the embryonic mouse cerebral cortex as a
      model system, we describe a simplified dual thymidine analogue protocol using
      BrdU and EdU that can be used to measure Ts and Tc. The advantage of this
      protocol over cumulative labeling approaches is that only a single time-point is
      required for measurement. An additional benefit of this protocol over existing
      dual-analog approaches (CldU/IdU) is the antibody-free detection of EdU and the
      acid-free detection of BrdU, processes allowing for the parallel use of specific
      antibodies so as to measure the cell-cycle in immunologically defined cellular
      subpopulations.

PMID- 29445898
TI  - Knowledge, Attitudes and Barriers to Human Papillomavirus (HPV) Vaccine Uptake
      Among an Immigrant and Refugee Catch-Up Group in a Western Canadian Province.
AB  - Vaccination is a key strategy to prevent cervical cancer in developed countries.
      Lower uptake of human papillomavirus (HPV) vaccine among new immigrants and
      refugees has been documented, although exploration of underlying reasons remains
      an understudied area. Semi-structured interviews with eleven immigrant women
      (ages 18-26 years) were conducted to understand their knowledge, attitudes and
      barriers regarding HPV vaccination in a western Canadian province. Participants
      had limited knowledge about HPV and the vaccine. Most women perceived that their
      risk of HPV was low, however expressed willingness to receive the vaccine if it
      were recommended by their physician. Greater efforts are needed to increase
      knowledge about HPV among immigrant and refugee women and support for physicians
      to discuss and offer vaccination to this underserved population.

PMID- 29445899
TI  - Aquarium Trade Supply-Chain Losses of Marine Invertebrates Originating from Papua
      New Guinea.
AB  - A major difficulty in managing live organism wildlife trade is often the reliance
      on trade data to monitor exploitation of wild populations. Harvested organisms
      that die or are discarded before a point of sale are regularly not reported. For
      the global marine aquarium trade, identifying supply-chain losses is necessary to
      more accurately assess exploitation from trade data. We examined quality control
      rejections and mortality of marine invertebrates (Asteroidea, Gastropoda,
      Malacostraca, Ophiuroidea) moving through the Papua New Guinea marine aquarium
      supply-chain, from fisher to importer. Utilizing catch invoices and exporter
      mortality records we determined that, over a 160 day period, 38.6% of the total
      invertebrate catch (n = 13,299 individuals) was lost before export. Supply-chain
      losses were divided among invertebrates rejected in the quality control process
      (11.5%) and mortality of the accepted catch in transit to, and during holding at,
      an export facility (30.6%). A further 0.3% died during international transit to
      importers. We quantified supply-chain losses for the ten most fished species
      which accounted for 96.4% of the catch. Quality control rejections (n = 1533)
      were primarily explained by rejections of oversized invertebrates (83.2% of
      rejections). We suggest that enforceable size limits on species prone to size
      based rejections and elimination of village-based holding of invertebrates would
      reduce losses along the Papua New Guinea supply-chain. This case study
      underscores that low mortality during international transit may mask large losses
      along supply-chains prior to export and exemplifies the limitations of trade data
      to accurately monitor exploitation.

PMID- 29445900
TI  - Clinical interpretation of pathogenic ATM and CHEK2 variants on multigene panel
      tests: navigating moderate risk.
AB  - Comprehensive genomic cancer risk assessment (GCRA) helps patients, family
      members, and providers make informed choices about cancer screening, surgical and
      chemotherapeutic risk reduction, and genetically targeted cancer therapies. The
      increasing availability of multigene panel tests for clinical applications allows
      testing of well-defined high-risk genes, as well as moderate-risk genes, for
      which the penetrance and spectrum of cancer risk are less well characterized.
      Moderate-risk genes are defined as genes that, when altered by a pathogenic
      variant, confer a 2 to fivefold relative risk of cancer. Two such genes included
      on many comprehensive cancer panels are the DNA repair genes ATM and CHEK2, best
      known for moderately increased risk of breast cancer development. However, the
      impact of screening and preventative interventions and spectrum of cancer risk
      beyond breast cancer associated with ATM and/or CHEK2 variants remain less well
      characterized. We convened a large, multidisciplinary, cross-sectional panel of
      GCRA clinicians to review challenging, peer-submitted cases of patients
      identified with ATM or CHEK2 variants. This paper summarizes the inter
      professional case discussion and recommendations generated during the session,
      the level of concordance with respect to recommendations between the academic and
      community clinician participants for each case, and potential barriers to
      implementing recommended care in various practice settings.

PMID- 29445901
TI  - Geology and geochemistry of the Atacama Desert.
AB  - The Atacama Desert, the driest of its kind on Earth, hosts a number of unique
      geological and geochemical features that make it unlike any other environment on
      the planet. Considering its location on the western border of South America,
      between 17 and 28  degrees S, its climate has been characterized as arid to
      hyperarid for at least the past 10 million years. Notably dry climatic conditions
      of the Atacama Desert have been related to uplift of the Andes and are believed
      to have played an important role in the development of the most distinctive
      features of this desert, including: (i) nitrates and iodine deposits in the
      Central Depression, (ii) secondary enrichment in porphyry copper deposits in the
      Precordillera, (iii) Li enrichment in salt flats of the Altiplano, and (iv) life
      in extreme habitats. The geology and physiography of the Atacama Desert have been
      largely shaped by the convergent margin present since the Mesozoic era. The
      geochemistry of surface materials is related to rock geochemistry (Co, Cr, Fe,
      Mn, V, and Zn), salt flats, and evaporite compositions in endorheic basins (As,
      B, and Li), in addition to anthropogenic activities (Cu, Mo, and Pb). The
      composition of surface water is highly variable, nonetheless in general it
      presents a circumneutral pH with higher conductivity and total dissolved solids
      in brines. Major water constituents, with the exception of HCO3-, are generally
      related to the increase of salinity, and despite the fact that trace elements are
      not well-documented, surface waters of the Atacama Desert are enriched in As, B,
      and Li when compared to the average respective concentrations in rivers
      worldwide.

PMID- 29445902
TI  - Natural product diversity of actinobacteria in the Atacama Desert.
AB  - The Atacama Desert of northern Chile is considered one of the most arid and
      extreme environment on Earth. Its core region was described as featuring "Mars
      like" soils that were at one point deemed too extreme for life to exist. However,
      recent investigations confirmed the presence of diverse culturable
      actinobacteria. In the current review, we discuss a total of 46 natural products
      isolated to date representing diverse chemical classes characterized from
      different actinobacteria isolated from various locations in the Atacama Desert.
      Their reported biological activities are also discussed.

PMID- 29445903
TI  - Movement Kinematics Dynamically Modulates the Rolandic ~ 20-Hz Rhythm During Goal
      Directed Executed and Observed Hand Actions.
AB  - This study investigates whether movement kinematics modulates similarly the
      rolandic alpha and beta rhythm amplitude during executed and observed goal
      directed hand movements. It also assesses if this modulation relates to the
      corticokinematic coherence (CKC), which is the coupling observed between cortical
      activity and movement kinematics during such motor actions.
      Magnetoencephalography (MEG) signals were recorded from 11 right-handed healthy
      subjects while they performed or observed an actor performing the same repetitive
      hand pinching action. Subjects' and actor's forefinger movements were monitored
      with an accelerometer. Coherence was computed between acceleration signals and
      the amplitude of alpha (8-12 Hz) or beta (15-25 Hz) oscillations. The coherence
      was also evaluated between source-projected MEG signals and their beta amplitude.
      Coherence was mainly observed between acceleration and the amplitude of beta
      oscillations at movement frequency within bilateral primary sensorimotor (SM1)
      cortex with no difference between executed and observed movements. Cross
      correlation between the amplitude of beta oscillations at the SM1 cortex and
      movement acceleration was maximal when acceleration was delayed by ~ 100 ms, both
      during movement execution and observation. Coherence between source-projected MEG
      signals and their beta amplitude during movement observation and execution was
      not significantly different from that during rest. This study shows that
      observing others' actions engages in the viewer's brain similar dynamic
      modulations of SM1 cortex beta rhythm as during action execution. Results support
      the view that different neural mechanisms might account for this modulation and
      CKC. These two kinematic-related phenomena might help humans to understand how
      observed motor actions are actually performed.

PMID- 29445904
TI  - Changes in density spectral array of bilateral BIS during carotid external
      compression in cardiac surgery.

PMID- 29445905
TI  - Correction to: The oxygen reserve index (ORI): a new tool to monitor oxygen
      therapy.
AB  - In the original publication of the article, the authors have realized an error in
      Fig. 1. The corrected version of Fig. 1 is given below.

PMID- 29445906
TI  - The Neuropsychological Consequences of Armed Conflicts and Torture.
AB  - PURPOSE OF REVIEW: At any point in time, there are hundreds of armed conflicts
      throughout the world. Neuropsychological disorders are a major cause of morbidity
      during and after armed conflicts. Conditions such as closed and open head
      injuries, acute stress disorder, post-traumatic stress disorder, depression,
      anxiety, and psychosis are prevalent among survivors. Herein, we summarize
      information on the various forms of torture, the resultant neuropsychological
      pathology, and treatment strategies to help survivors. RECENT FINDINGS:
      Strategies to address the needs of individuals who experienced neuropsychological
      trauma due to armed conflicts and torture include pharmacological and
      psychological interventions. The former includes antidepressant, antianxiety, and
      antipsychotic medications. The latter includes narrative exposure therapy and
      trauma-focused cognitive-behavioral therapy. Neuropsychological disorders are
      major causes of morbidity among survivors of armed conflicts and torture.
      Treatment strategies must be affordable, applicable across cultures, and
      deliverable by individuals who understand the victims' psychosocial and ethnic
      background.

PMID- 29445907
TI  - Management of Serrated Polyps of the Colon.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize the management of
      serrated colorectal polyps (SPs), with a particular focus on the most common
      premalignant SP, sessile serrated adenoma or polyp (SSA/P). These lesions present
      a challenge for endoscopists with respect to detection and resection, and are
      also susceptible to pathologic misdiagnosis. RECENT FINDINGS: Patients with
      SSA/Ps are at an increased risk of future colorectal neoplasia, including
      advanced polyps and cancer. Reasonable benchmarks for SP detection rates are 5-7%
      for SSA/Ps and 10-12% for proximal SPs. Certain endoscopic techniques such as
      chromoendoscopy, narrow band imaging, water immersion, and wide-angle viewing may
      improve SSA/P detection. Emerging endoscopic techniques such as underwater
      polypectomy, suction pseudopolyp technique, and piecemeal cold snare polypectomy
      are helpful tools for the endoscopist's armamentarium for removing SSA/Ps. Proper
      orientation of SSA/P specimens can improve the accuracy of pathology readings.
      Patients with confirmed SSA/Ps and proximal HPs should undergo surveillance at
      intervals similar to what is recommended for patients with conventional adenomas.
      Patients with SSA/Ps may also be able to lower their risk of future polyps by
      targeting modifiable risk factors including tobacco and alcohol use and high-fat
      diets. NSAIDs and aspirin appear to be protective agents. SPs and SSA/Ps in
      particular are important colorectal cancer precursors that merit special
      attention to ensure adequate detection, resection, and surveillance.

PMID- 29445909
TI  - The relationship among preconception depression, anxiety, and social support of
      the reproductive-aged women in China.
AB  - The reproductive-aged women have to face physiological and psychological
      challenges as long as they plan to conceive. However, most previous studies
      focused on depression and anxiety during pregnancy. This study aimed to
      investigate the association among preconception depression, anxiety, and social
      support of the Chinese reproductive-aged women. Nine-hundred five reproductive
      aged women who planned to conceive for the first or second time in the next three
      months were recruited through the Maternity and Child Healthcare Hospital and
      Obstetrics and Gynecology Hospital from three provinces in China. Social Support
      Rating Scale, Self-Rating Depression Scale, and Self-Rating Anxiety Scale were
      used in this study. The hierarchical regression model was employed to examine the
      prediction effect of the three sub-dimensions of social support on preconception
      depression and anxiety. Of the reproductive-aged women, 25.86 and 13.04% had
      preconception depression and anxiety symptoms. Nearly all reproductive-aged women
      had moderate and high social support before pregnancy. The significant
      differences in depression and anxiety among different levels of occupation and
      monthly income were found. For depression and anxiety, objective support, support
      availability, and subjective support simultaneously entered into the model still
      could significantly explain 5.9 and 6.7% of variations after controlling for the
      demographic variables, respectively. According to this study, there were
      significant correlations among preconception depression, anxiety, and social
      support. And objective support, support availability, and subjective support
      could negatively predict preconception depression and anxiety. Attaching
      importance to the preconception mental health and social support can provide
      effective scientific support for helping women fully understand and effectively
      use the social resources, and scientifically prepare for pregnancy.

PMID- 29445908
TI  - Gender Differences in Epidemiology, Pathophysiology, and Treatment of
      Hypertension.
AB  - PURPOSE OF REVIEW: This review aims to examine gender differences in both the
      epidemiology and pathophysiology of hypertension and to explore gender
      peculiarities on the effects of antihypertensive agents in decreasing BP and CV
      events. RECENT FINDINGS: Men and women differ in prevalence, awareness, and
      control rate of hypertension in an age-dependent manner. Studies suggest that sex
      hormones changes play a pivotal role in the pathophysiology of hypertension in
      postmenopausal women. Estrogens influence the vascular system inducing
      vasodilatation, inhibiting vascular remodeling processes, and modulating the
      renin-angiotensin aldosterone system and the sympathetic system. This leads to a
      protective effect on arterial stiffness during reproductive age that is
      dramatically reversed after menopause. Data on the efficacy of antihypertensive
      therapy between genders are conflicting, and the underrepresentation of aged
      women in large clinical trials could influence the results. Therefore, further
      clinical research is needed to uncover potential gender differences in
      hypertension to promote the development of a gender-oriented approach to
      antihypertensive treatment.

PMID- 29445910
TI  - 1H, 13C and 15N resonance assignment of domain 1 of trans-activation response
      element (TAR) RNA binding protein isoform 1 (TRBP2) and its comparison with that
      of isoform 2 (TRBP1).
AB  - TAR RNA binding protein (TRBP) is a double-stranded RNA binding protein involved
      in various biological processes like cell growth, development, death, etc. The
      protein exists as two isoforms TRBP2 and TRBP1. TRBP2 contains additional 21
      amino acids at its N-terminus, which are proposed to be involved in its membrane
      localization, when compared to TRBP1. The resonance assignment (19-228) of the
      double-stranded RNA binding domains (dsRBD 1 and 2) of TRBP2 has been reported
      earlier. Here, we report 1H, 13C and 15N resonance assignment for dsRBD1 of TRBP2
      (1-105) containing the additional N-terminal residues. This assignment will
      provide deeper insights to understand the effect of these residues on the
      structure and dynamics of TRBP2 and would therefore help in further elucidating
      the differences in the role of these isoforms.

PMID- 29445911
TI  - High prevalence of HCV (GT4)-related TSH abnormality among 13402 Egyptian
      patients treated with direct acting antiviral therapy.
AB  - BACKGROUND: HCV is associated with several extra hepatic diseases including
      thyroid dysfunction. This study aims at evaluating prevalence of thyroid
      dysfunction and its possible predictors in a large cohort of HCV GT4-infected
      patients, and the role of thyroid dysfunction as a predictor of response in the
      setting of direct acting antivirals (DAAs). METHODS: Patients registered on the
      web-based registry system to receive therapy for chronic HCV in Beheira
      governorate viral hepatitis specialized treatment center affiliated to the
      National committee for control of viral hepatitis (NCCVH), Ministry of health,
      Egypt in the period from January 2015 to October 2016. Their data were exported
      and analyzed for the prevalence of thyroid dysfunction and its associated
      variables. RESULTS: Out of 13,402 patients, 2833 (21.1%) had elevated TSH level >
      4.5 mIU/l (hypothyroidism). Female gender (62.7%), older age, higher FIB4, AST,
      and BMI and lower albumin were significantly associated with elevated TSH level
      on univariate analysis, while liver stiffness measured by fibroscan was not
      significantly associated. On the other hand, 466 patients (3.5%) showed low TSH
      level < 0.4 mIU/l (hyperthyroidism). Older age (median 52 years) and male gender
      (51.5%) were the only significantly associated variables. No association was
      found between SVR and baseline TSH level. Follow-up of 236 patients after SVR
      revealed improvement in TSH level in 80% of them. CONCLUSION: Hypothyroidism is
      prevalent in patients with chronic HCV GT4, and is influenced by patient gender
      and age. Pretreatment TSH does not affect SVR after DAAs. Despite limited data
      SVR achievement after DAAs improves thyroid dysfunction.

PMID- 29445912
TI  - Plasma elemental responses to red meat ingestion in healthy young males and the
      effect of cooking method.
AB  - PURPOSE: Elemental deficiencies are highly prevalent and have a significant
      impact on health. However, clinical monitoring of plasma elemental responses to
      foods remains largely unexplored. Data from in vitro studies show that red meat
      (beef) is a highly bioavailable source of several key elements, but cooking
      method may influence this bioavailability. We therefore studied the postprandial
      responses to beef steak, and the effects of two different cooking methods, in
      healthy young males. METHODS: In a randomized cross-over controlled trial,
      healthy males (n = 12, 18-25 years) were fed a breakfast of beef steak (270 +/-
      20 g) in which the meat was either pan-fried (PF) or sous-vide (SV) cooked.
      Baseline and postprandial blood samples were collected and the plasma
      concentrations of 15 elements measured by inductively coupled plasma-mass
      spectrometry (ICP-MS). RESULTS: Concentrations of Fe and Zn changed after meal
      ingestion, with plasma Fe increasing (p < 0.001) and plasma Zn decreasing (p <
      0.05) in response to both cooking methods. The only potential treatment effect
      was seen for Zn, where the postprandial area under the curve was lower in
      response to the SV meal (2965 +/- 357) compared to the PF meal (3190 +/- 310; p <
      0.05). CONCLUSIONS: This multi-element approach demonstrated postprandial
      responsiveness to a steak meal, and an effect of the cooking method used. This
      suggests the method would provide insight in future elemental metabolic studies
      to evaluate responses to meat-based meals, including longer-term interventions in
      more specifically defined cohorts to clearly establish the role of red meat as an
      important source of elements.

PMID- 29445913
TI  - Dietary pattern associated with selenoprotein P and MRI-derived body fat volumes,
      liver signal intensity, and metabolic disorders.
AB  - PURPOSE: The association of complex dietary patterns with circulating
      selenoprotein P (SELENOP) levels in humans is unknown. In a general population
      sample, we aimed to identify a dietary pattern explaining inter-individual
      variation in circulating SELENOP concentrations and to study this pattern in
      relation to prevalent diabetes, metabolic syndrome (MetS), MRI-determined total
      volumes of visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, and
      liver signal intensity/fatty liver disease. METHODS: In this cross-sectional
      study, serum SELENOP levels were measured in 853 individuals. In a subsample of
      553 participants, whole-body MRI was performed to assess body fat distribution
      and liver fat. Dietary intake was assessed by a self-administered food frequency
      questionnaire and the dietary pattern identified using reduced-rank regression
      (RRR). Multivariable linear and logistic regressions were used to investigate
      associations between dietary pattern score and metabolic traits. RESULTS:
      Characterized by high intake of fruit, vegetables and antioxidant beverages, the
      RRR-derived dietary pattern displayed inverse associations with VAT, SAT, MetS,
      and prevalent diabetes in multivariable-adjusted restricted cubic splines. Each
      unit increase in dietary pattern score was associated with 31% higher SELENOP
      levels, 12% lower VAT (95% CI: - 19%; - 5%), 13% (95% CI: - 20%; - 6%) lower SAT
      values and 46% (95% CI: 27%; 60%) and 53% (95% CI: 22%; 72%) lower odds of having
      MetS or diabetes, respectively. No meaningful relations were observed between the
      dietary pattern and liver traits. CONCLUSIONS: Our observations propose diet
      related regulation in SELENOP levels and that the identified dietary pattern is
      inversely related to VAT, SAT, MetS, and prevalent diabetes.

PMID- 29445914
TI  - Interaction between dietary acrylamide intake and genetic variants for estrogen
      receptor-positive breast cancer risk.
AB  - PURPOSE: The association between dietary acrylamide intake and estrogen receptor
      positive (ER+) breast cancer risk in epidemiological studies is inconsistent. By
      analyzing gene-acrylamide interactions for ER+ breast cancer risk, we aimed to
      clarify the role of acrylamide intake in ER+ breast cancer etiology. METHODS: The
      prospective Netherlands Cohort Study on diet and cancer includes 62,573 women,
      aged 55-69 years. At baseline, a random subcohort of 2589 women was sampled from
      the total cohort for a case-cohort analysis approach. Dietary acrylamide intake
      of subcohort members (n = 1449) and ER+ breast cancer cases (n = 844) was
      assessed with a food frequency questionnaire. We genotyped single nucleotide
      polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems,
      oxidative stress and DNA repair. Multiplicative interaction between acrylamide
      intake and SNPs was assessed with Cox proportional hazards analysis, based on
      20.3 years of follow-up. RESULTS: Unexpectedly, there was a statistically non
      significant inverse association between acrylamide and ER+ breast cancer risk
      among all women but with no clear dose-response relationship, and no association
      among never smokers. Among the results for 57 SNPs and 2 gene deletions,
      rs1056827 in CYP1B1, rs2959008 and rs7173655 in CYP11A1, the GSTT1 gene deletion,
      and rs1052133 in hOGG1 showed a statistically significant interaction with
      acrylamide intake for ER+ breast cancer risk. CONCLUSIONS: This study did not
      provide evidence for a positive association between acrylamide intake and ER+
      breast cancer risk. If anything, acrylamide was associated with a decreased ER+
      breast cancer risk. The interaction with SNPs in CYP1B1 and CYP11A1 suggests that
      acrylamide may influence ER+ breast cancer risk through sex hormone pathways.

PMID- 29445915
TI  - Correction to: Association of main folate metabolic pathway gene polymorphisms
      with neural tube defects in Han population of Northern China.
AB  - The original version of this article unfortunately contained an error.

PMID- 29445916
TI  - Bottom-of-sulcus focal cortical dysplasia presenting as epilepsia partialis
      continua multimodality characterization including 7T MRI.
AB  - INTRODUCTION: Bottom-of-sulcus focal cortical dysplasias are an under recognized,
      surgically treatable cause of focal epilepsy. Resection can dramatically reduce
      the seizure burden for children with refractory epilepsy, or eliminate seizures
      altogether. MATERIAL AND METHODS: We report the case and present the results of
      multimodality evaluation of a 15-year-old young man who presented with long
      standing partial epilepsy affecting his right leg, which over the years became
      refractory to therapy. RESULTS: High-resolution 3T MRI images acquired as a
      dedicated epilepsyprotocol were initially interpreted as unremarkable. On further
      review by an experienced specialist aware of clinical and electroencephalographic
      findings, a subtle focal cortical dysplasia was identified at the bottom of a
      sulcus near the medial aspect of the left precentral gyrus. After confirmation of
      the extent of the lesion with PET and ultra-high field 7T MRI, the patient
      underwent cortical mapping and focal resection and remains free of seizures.
      COCLUSIONS: This case emphasizes the need for a multidisciplinary approach to the
      evaluation of refractory focal epilepsy in children and highlights the potential
      role of ultra-high field 7T MRI in identifying the often subtle causative
      anatomic abnormalities.

PMID- 29445917
TI  - Thirty-day outcome in pediatric epilepsy surgery.

PMID- 29445918
TI  - Persistent craniopharyngeal canal, bilateral microphthalmia with colobomatous
      cysts, ectopic adenohypophysis with Rathke cleft cyst, and ectopic
      neurohypophysis: case report and review of the literature.
AB  - INTRODUCTION: Persistent craniopharyngeal canal (PCC) is a rare anomaly of the
      base of the skull. PCC is defined as a well-corticated osseous canal, extending
      from the roof of the nasopharynx to the base of the sella over the course of the
      sphenoid corpus. We reported a PCC case with unique associations. The magnetic
      resonance imaging findings are discussed. CASE PRESENTATION: We report a case of
      a 2-year-old boy with persistent craniopharyngeal canal, bilateral microphtalmia
      with large colobomatous cyst, and ectopic adenohypophysis with Rathke cleft cyst.
      He also has ectopic neurohypophysis and optic atrophy. CONCLUSION: The presence
      of orbital and optic tract malformations, craniofacial and intracranial
      anomalies, and tumors can accompany craniopharyngeal canals (CCs). MRI is helpful
      in the evaluation of PCC and associated anomalies in these patients.

PMID- 29445919
TI  - Appraisal of clinical practice guidelines on the management of hypothyroidism in
      pregnancy using the Appraisal of Guidelines for Research and Evaluation II
      instrument.
AB  - PURPOSE: This study aimed to systematically evaluate the quality of guidelines
      for the management of hypothyroidism in pregnancy. METHOD: Systematic searches
      were conducted to identify hypothyroidism in pregnancy guidelines published in
      electronic databases and developers' websites. Four reviewers independently
      evaluated eligible guidelines using the Appraisal of Guidelines for Research and
      Evaluation II (AGREE II) instrument. Agreement among reviewers was measured using
      the intraclass correlation coefficient (ICC). The number of recommendations,
      strength of recommendations, and levels of evidence were determined. The software
      used for analysis was SPSS version 12.0. RESULTS: Nine guidelines met the
      inclusion criteria and were appraised. The scope and purpose (65%) and clarity of
      presentation (70%) domains achieved relatively high scores, whereas the
      stakeholder involvement (41%), rigor of development (33%), applicability (36%),
      and editorial independence (31%) domains yielded low scores. The American Thyroid
      Association (ATA) guideline ranked the highest, whereas the 2012 Chinese Society
      of Endocrinology (CSE) guideline ranked the lowest among all the guidelines. The
      British Thyroid Association (BTA) and ATA guidelines were strongly recommended as
      dependable and helpful references to aid clinical decisions for medical
      providers, whereas the CSE guideline was not recommended. Most recommendations of
      the guidelines were relatively consistent. However, the nine guidelines varied
      with respect to their recommendations on thyroid scanning, dose of levothyroxine
      (L-T4) treatment, and target thyroid-stimulating hormone(TSH) level of L-T4
      therapy. CONCLUSIONS: The quality of the guidelines on the management of
      hypothyroidism in pregnancy is highly variable. Additionally, these guidelines
      need significant improvement, especially in the rigor of development and
      applicability domains. Some improvements should be made to promote the
      development and implementation of guidelines, for example, conducting a
      comprehensive search strategy to include more potential evidence and establishing
      a standard grading system to evaluate the quality of evidence.

PMID- 29445921
TI  - Spontaneous Regression and Resolution of Breast Implant-Associated Anaplastic
      Large Cell Lymphoma: Implications for Research, Diagnosis and Clinical
      Management.
AB  - BACKGROUND: First described in 1997, breast implant-associated anaplastic large
      cell lymphoma (BIA-ALCL) was recognised by the World Health Organisation in 2016
      as a specific disease. It typically presents as a late seroma-containing
      atypical, monoclonal T cells which are CD30+ and anaplastic lymphoma kinase
      negative. Until recently, it was thought that the disease was very rare. However,
      it is being diagnosed increasingly frequently with 56 cases confirmed in
      Australia by September 2017 and the estimated incidence revised from 1 in 300,000
      to between 1 in 1000 and 1 in 10,000 patients with bilateral implants. There is
      debate about the spectrum of BIA-ALCL. According to the current WHO
      classification, BIA-ALCL is a cancer in all cases. Treatment guidelines require
      that it is treated urgently with a minimum of bilateral removal of implants and
      capsulectomies. Whilst acknowledging the disease has been under diagnosed in the
      past, with some notable exceptions the BIA-ALCL literature has given scant
      attention to the epidemiological evidence. Now that it is known that the disease
      may occur in up to 1 in 1000 patients with a median of 7.5 years from
      implantation to diagnosis, understanding it in its epidemiological context is
      imperative. The epidemiology of cancer and lymphoma in women with breast implants
      strongly suggests that most patients do not have a cancer that will inevitably
      progress without treatment but instead a self-limiting lympho-proliferative
      disorder. Although the possibility of spontaneous regression has been raised and
      the observation made that treatment delay did not seem to increase the risk of
      spread, the main objection to the lympho-proliferative hypothesis has been the
      lack of documented cases of spontaneous regression or resolution. Because all
      cases currently are considered malignant and treated urgently, only case report
      evidence, interpreted in the proper epidemiological context, is likely to be
      available to challenge this thinking. METHODS AND RESULTS: New observations and
      interpretation of the epidemiology of BIA-ALCL are made. These are supported by
      the presentation of two cases, which to the best of our knowledge comprise the
      first documented evidence of spontaneous regression and spontaneous resolution of
      confirmed BIA-ALCL. CONCLUSIONS: The epidemiology of the disease strongly
      suggests that the vast majority of cases are not a cancer that will inevitably
      progress without treatment. The findings presented in the manuscript provide
      supportive clinical evidence. Consequently, an alternative view of BIA-ALCL with
      implications for research, diagnosis and clinical management needs to be
      considered. 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- 29445920
TI  - Phylogenetic Diversity and In Vitro Susceptibility Profiles of Human Pathogenic
      Members of the Fusarium fujikuroi Species Complex Isolated from South India.
AB  - Availability of molecular methods, gene sequencing, and phylogenetic species
      recognition have led to rare fungi being recognized as opportunistic pathogens.
      Fungal keratitis and onychomycosis are fairly common mycoses in the tropics,
      especially among outdoor workers and enthusiasts. The frequently isolated
      etiological agents belong to genera Candida, Aspergillus, and Fusarium. Within
      the genus Fusarium, known to be recalcitrant to prolonged antifungal treatment
      and associated with poor outcome, members of the Fusarium solani species complex
      are reported to be most common, followed by members of the Fusarium oxysporum SC
      and the Fusarium fujikuroi SC (FFSC). Morphological differentiation among the
      various members is ineffective most times. In the present study, we describe
      different species of the FFSC isolated from clinical specimen in south India. All
      twelve isolates were characterized up to species level by nucleic acid sequencing
      and phylogenetic analysis. The molecular targets chosen were partial regions of
      the internal transcribed spacer rDNA region, the panfungal marker and translation
      elongation factor-1alpha gene, the marker of choice for Fusarium speciation.
      Phylogenetic analysis was executed using the Molecular Evolutionary Genetics
      Analysis software (MEGA7). In vitro susceptibility testing against amphotericin
      B, voriconazole, posaconazole, natamycin, and caspofungin diacetate was performed
      following the CLSI M38-A2 guidelines for broth microdilution method. The twelve
      isolates of the FFSC were F. verticillioides (n = 4), F. sacchari (n = 3), F.
      proliferatum (n = 2), F. thapsinum (n = 1), F. andiyazi (n = 1), and F.
      pseudocircinatum (n = 1). To the best of our knowledge, this is the first report
      of F. andiyazi from India and of F. pseudocircinatum as a human pathogen
      worldwide. Natamycin and voriconazole were found to be most active agents
      followed by amphotericin B. Elderly outdoor workers figured more among the
      patients and must be recommended protective eye wear.

PMID- 29445922
TI  - Education on the Business of Plastic Surgery During Training: A Survey of Plastic
      Surgery Residents.
AB  - BACKGROUND: Entrepreneurial skills are important for physicians, especially
      plastic surgeons. Nevertheless, these skills are not typically emphasized during
      residency training. OBJECTIVE: Evaluate the extent of business training at
      plastic surgery residency programs as well as means of enhancing business
      training. METHODS: A 6-question online survey was sent to plastic surgery program
      directors for distribution to plastic surgery residents. Responses from residents
      at the PGY2 level and above were included for analysis. Tables were prepared to
      present survey results. RESULTS: Hundred and sixty-six residents including 147
      PGY2 and above residents responded to our survey. Only 43.5% reported inclusion
      of business training in their plastic surgery residency. A majority of residents
      reported they do not expect on graduation to be prepared for the business aspects
      of plastic surgery. Additionally, a majority of residents feel establishment of a
      formal lecture series on the business of plastic surgery would be beneficial.
      CONCLUSIONS: Results from our survey indicate limited training at plastic surgery
      programs in necessary business skills. Plastic surgery residency programs should
      consider incorporating or enhancing elements of business training in their
      curriculum. 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- 29445924
TI  - Correction to: The use of PIPAC (pressurized intraperitoneal aerosol
      chemotherapy) in gynecological oncology: a statement by the Arbeitsgemeinschaft
      Gynaekologische Onkologie (AGO) Kommission Ovar, AGO Study Group, North-Eastern
      German Society of Gynaecologic Oncology (NOGGO), AGO Austria and AGO Switzerland.
AB  - The title of the article has been published incorrectly. The correct title is
      given below.

PMID- 29445923
TI  - Inpatient outcomes of preterm infants receiving omega-3 enriched lipid emulsion
      (SMOFlipid): an observational study.
AB  - : Neonatal units have started to switch from using conventional soy-based to
      alternate lipid emulsions, like SMOFlipid. SMOFlipid has been associated with an
      improvement in biochemical parameters and delays progression of parenteral
      nutrition-associated liver disease (PNALD). This retrospective epoch study aimed
      to compare clinically relevant neonatal outcomes in preterm infants (< 32 weeks),
      receiving SMOFlipid versus Intralipid. We compared clinical outcomes in two
      epochs-epoch 1 (Intralipid, October 2013-June 2015) versus epoch 2 (SMOFlipid,
      July 2015-March 2017). Primary outcome studied was mortality and rates of severe
      neonatal morbidities. Univariate and multivariate regression was conducted to
      determine risk for mortality and PNALD. A total of 222 infants (epoch 1, 123
      versus epoch 2, 99) were included in the study. A higher incidence of late onset
      sepsis (56 versus 30%, p < 0.005) was observed in epoch 1. There was no
      significant difference in mortality or rates of any other severe neonatal
      morbidity. The type of lipid emulsion did not have a significant effect on
      mortality or PNALD on regression analysis. CONCLUSION: Use of SMOFlipid as the
      primary lipid emulsion seems to have minimal effect on rates of clinically
      important neonatal outcomes; however, long-term effects need to be further
      evaluated. What is Known: * Many neonatal units have started replacing
      traditional soy-based lipid formulations with SMOFlipid (omega-3 enriched lipid
      emulsion), as the primary lipid component in parenteral nutrition for preterm
      infants. * While there is evidence associating improved liver function and
      balanced essential fatty acid levels in infants receiving SMOFlipid, there is a
      lack of evidence evaluating relevant clinical outcomes in infants receiving
      SMOFlipid versus traditional lipid formulations. What is New: * The influence of
      SMOFlipid on a series of clinical outcomes in an at-risk preterm population is
      presented. * SMOFlipid appears to be well tolerated in preterm infants with
      minimal side effects, and some growth benefits seen.

PMID- 29445925
TI  - Tubal restorative surgery for hydrosalpinges in women due to in vitro
      fertilization.
AB  - OBJECTIVE: The study was carried out to clarify the IVF outcome after
      laparoscopic neosalpingostomy for infertile patients affected by hydrosalpinx
      stage III. MATERIALS AND METHODS: From January 2010 to June 2015, 91 subjects of
      hydrosalpinx stage III were treated in out center by laparoscopic surgery before
      IVF cycle. 43 underwent neosalpingostomy (group 1) and the remaining 48 underwent
      salpingestomy (group 2). We compared these patients and their IVF outcomes after
      two different surgical techniques. RESULTS: There were no significant differences
      between the two groups, except a higher number of patients with bilaterial
      hydrosalpinges was noted in the neosalpingostomy group (79.1% vs. 56.3%,
      respectively). 25 patients with neosalpingostomy and 29 with salpingectomy
      achieved pregnancy by IVF. The ongoing pregnancy rate per cycle in group 1 and
      group 2 was 51.1 and 47.2%, respectively. Two cases of ampullary ectopic
      pregnancies were noted in group 1 and one case of right tube interstitial
      pregnancy in group 2. No significant difference was observed in live birth rate
      between the groups (48.9% vs. 45.3%, respectively). CONCLUSIONS: The outcomes of
      IVF after neosalpingostomy were matchable with salpingectomy. For patients desire
      to preserve fallopian tubes, we recommend laparoscopic neosalpingostomy as an
      alternative choice to manage moderate hydrosalpinx before IVF.

PMID- 29445927
TI  - Advantage of 18F-PSMA-1007 over 68Ga-PSMA-11 PET imaging for differentiation of
      local recurrence vs. urinary tracer excretion.

PMID- 29445926
TI  - Single versus double-balloon catheters for the induction of labor of singleton
      pregnancies: a meta-analysis of randomized and quasi-randomized controlled
      trials.
AB  - OBJECTIVE: To compare the efficacy of single- versus double-balloon catheter (SBC
      vs. DBC) for cervical ripening and labor induction with an unfavorable cervix.
      METHODS: Systematic review and meta-analysis of randomized controlled trials
      (RCTs) or quasi-RCTs (qRCT) regarding the use of SBC or DBC for labor induction
      of live singleton cephalic pregnancies (>= 35 weeks) of any parity with an unripe
      cervix (Bishop score <= 6). Nine research databases were searched for original
      articles published in all languages up to November 2017 comparing both devices
      for labor induction. Five RCTs and one qRCT were included. Primary outcome
      measures were time from intervention (device placement) to birth time, vaginal
      delivery and cesarean section rates, and maternal satisfaction with the
      procedure. Risk of bias was evaluated with the Cochrane tool. Random effects
      models were used to combine data for meta-analyses. Summary measures were
      reported as mean differences and risk ratios (RR) with 95% confidence intervals.
      RESULTS: Regardless of parity, pooled analyses of the six trials (n = 1060 women)
      found that mean intervention to birth time, vaginal delivery and cesarean section
      rates, and maternal satisfaction to the procedure were similar for both studied
      groups (SBC vs. DBC). CONCLUSION: Measured primary outcome measures were similar
      regardless of the type of device used for labor induction of singleton
      pregnancies.

PMID- 29445928
TI  - Efficacy and safety of trastuzumab, lapatinib, and paclitaxel neoadjuvant
      treatment with or without prolonged exposure to anti-HER2 therapy, and with or
      without hormone therapy for HER2-positive primary breast cancer: a randomised,
      five-arm, multicentre, open-label phase II trial.
AB  - BACKGROUND: Dual blockade of HER2 promises increased pathological complete
      response (pCR) rate compared with single blockade in the presence of chemotherapy
      for HER2-positive (+) primary breast cancer. Many questions remain regarding
      optimal duration of treatment and combination impact of endocrine therapy for
      luminal HER2 disease. METHODS: We designed a randomised phase II, five-arm study
      to evaluate the efficacy and safety of lapatinib and trastuzumab (6 weeks)
      followed by lapatinib and trastuzumab plus weekly paclitaxel (12 weeks)
      with/without prolongation of anti-HER2 therapy prior to chemotherapy (18 vs. 6
      weeks), and with/without endocrine therapy in patients with HER2+ and/or
      oestrogen receptor (ER)+ disease. The primary endpoint was comprehensive pCR
      (CpCR) rate. Among the secondary endpoints, pCR (yT0-isyN0) rate, safety, and
      clinical response were evaluated. RESULTS: In total, 215 patients were enrolled;
      212 were included in the full analysis set (median age 53.0 years; tumour size =
      T2, 65%; and tumour spread = N0, 55%). CpCR was achieved in 101 (47.9%) patients
      and was significantly higher in ER- patients than in ER+ patients (ER- 63.0%, ER+
      36.1%; P = 0.0034). pCR with pN0 was achieved in 42.2% of patients (ER- 57.6%,
      ER+ 30.3%). No significant difference was observed in pCR rate between prolonged
      exposure groups and standard groups. Better clinical response outcomes were
      obtained in the prolongation phase of the anti-HER2 therapy. No surplus was
      detected in pCR rate by adding endocrine treatment. No major safety concern was
      recognised by prolonging the anti-HER2 treatment or adding endocrine therapy.
      CONCLUSIONS: This study confirmed the therapeutic impact of lapatinib,
      trastuzumab, and paclitaxel therapy for each ER- and ER+ subgroup of HER2+
      patients. Development of further strategies and tools is required, particularly
      for luminal HER2 disease.

PMID- 29445929
TI  - Prevalence of Leptospira serogroup-specific antibodies in cattle associated with
      reproductive problems in endemic states of India.
AB  - In this study, the seroprevalence and distribution of Leptospira in dairy cattle
      in endemic states of India were investigated in association with reproductive
      problems of the cattle. A total of 373 cattle serum samples from 45 farms in
      Maharashtra, Gujarat, Andhra Pradesh, Telangana, Karnataka, Tamil Nadu, Punjab,
      Haryana, Chhattisgarh, Sikkim and Uttarakhand states were collected from animals
      with a history of reproductive disorders like abortion, repeat breeding,
      anoestrus and endometritis, and also from apparently healthy animals. These
      samples were screened for Leptospira serogroup-specific antibodies by microscopic
      agglutination test (MAT) using a panel of 18 live reference serovar antigens. The
      seropositivity of 70.51% (263/373, 95% CI 0.65 to 0.75) was associated with
      reproductive problems (chi2 = 55.71, p < 0.01) and sampled states (chi2 = 32.99,
      p < 0.01) and independent of apparently healthy animals (chi2 = 15.6, p > 0.10)
      and age groups of cattle (chi2 = 0.91, p > 0.10). Further, the odds (risk
      relation) of reproductive disorders was 5.29 compared to apparently healthy
      animals (0.25 odds). The frequency distribution of predominant serogroup-specific
      Leptospira antibodies were determined against the serovars: Hardjo (27.76%),
      Pyrogenes (18.63%), Canicola and Javanica (17.49%), Hebdomadis (17.11%), Shermani
      and Panama (16.73%), Djasiman (16.35%), Tarassovi, Grippotyphosa and Pomona
      (15.97%), Icterohaemorrhagiae (15.59%), Copenhageni (14.83%), Australis (13.69%),
      Kaup and Hurstbridge (10.65%), Bankinang (10.27%) and Bataviae (9.51%). In
      conclusion, dairy cattle have a role in maintaining important several serovars
      besides well-known Hardjo serovar in endemic states of India and warrant
      mitigating measures to reduce the incidence of cattle leptospirosis including
      need for an intensive surveillance programme, preventive vaccination and control
      strategies.

PMID- 29445931
TI  - A rare case of pelvic bone duplication.
AB  - Iliac bone malformations are rare and result from early disturbance of the
      genetic and epigenetic processes that come together to form the pelvic girdle. We
      report the case of a 5-month-old boy found to have a duplication of the ilium and
      describe the likely causes of this very rare malformation.

PMID- 29445930
TI  - ZBTB17 loss-of-function mutation contributes to familial dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is a common primary myocardial disease leading to
      congestive heart failure, arrhythmia and sudden cardiac death. Increasing studies
      demonstrate substantial genetic determinants for DCM. Nevertheless, DCM is of
      substantial genetic heterogeneity, and the genetic basis for DCM in most patients
      remains unclear. The present study was sought to investigate the association of a
      genetic variant in the ZBTB17 gene with DCM. A cohort of 158 unrelated patients
      with idiopathic DCM and a total of 230 unrelated, ethnically matched healthy
      individuals used as controls were recruited. The coding exons and splicing
      boundaries of ZBTB17 were sequenced in all study participants. The functional
      effect of the mutant ZBTB17 was characterized by a dual-luciferase reporter assay
      system. A novel heterozygous ZBTB17 mutation, p.E243X, was discovered in an index
      patient. Genetic scan of the mutation carrier's available relatives showed that
      the mutation was present in all affected family members but absent in unaffected
      family members. Analysis of the proband's pedigree revealed that the mutation co
      segregated with DCM, which was transmitted in an autosomal dominant pattern with
      complete penetrance. The nonsense mutation was absent in the 460 control
      chromosomes. Functional assays demonstrated that the truncated ZBTB17 protein had
      no transcriptional activity as compared with its wild-type counterpart. This
      study firstly associates ZBTB17 loss-of-function mutation with enhanced
      susceptibility to DCM in humans, which provides novel insight into the molecular
      mechanism underpinning DCM, implying potential implications for genetic
      counseling and personalized management of DCM.

PMID- 29445932
TI  - Fibrodysplasia ossificans progressiva: a current review of imaging findings.
AB  - OBJECTIVE: Fibrodysplasia ossificans progressiva is a rare genetic disorder
      characterized by congenital skeletal deformities and soft tissue masses that
      progress to heterotopic ossification. Deformities of the great toes are
      distinctive, and heterotopic ossification in the soft tissues follows an expected
      anatomic and temporal pattern. In addition to heterotopic ossification,
      osteochondromata, middle ear ossification, demyelination, lymphedema, and venous
      thrombosis are characteristic. Awareness of this constellation of findings is
      important to early diagnosis and surveillance. CONCLUSIONS: Recognition of the
      imaging manifestations of fibrodysplasia ossificans progressiva is imperative to
      early diagnosis in order to appropriately direct patient care and preclude
      unnecessary biopsies or surgical procedures.

PMID- 29445933
TI  - Multimodality imaging of subacromial impingement syndrome.
AB  - Subacromial impingement syndrome results from irritation of the tendons of the
      rotator cuff muscles in the subacromial space and may manifest as a range of
      pathologies. However, subacromial impingement is a dynamic condition for which
      imaging reveals predisposing factors but no pathognomonic indicators. Also, the
      usual imaging features of subacromial impingement may be seen in symptomatic and
      asymptomatic patients. Therefore, imaging is able to detect tears and describe
      the risk factors of impingement but cannot confirm subacromial impingement.
      Radiographs allow assessment of the morphology of the acromion and its lateral
      extension by means of the acromial index and the critical shoulder angle, which
      may increase in cases of subacromial impingement. Ultrasound is necessary to
      evaluate a tendon tear and is the only tool that provides dynamic information,
      which is essential to assessing dynamic conditions. Magnetic resonance imaging
      (MRI) allows the assessment of associated intraarticular abnormalities, joint
      effusion, and bone marrow edema. The objective of this article is to provide an
      overview of the pathophysiology and clinical manifestations of subacromial
      impingement and discuss recent advances in the imaging of subacromial impingement
      and the role of radiography, ultrasound, and MRI in differentiating normal from
      pathologic findings.

PMID- 29445934
TI  - Serum Surfactant Protein Levels in Patients Admitted to the Hospital with Acute
      COPD Exacerbation.
AB  - Surfactant proteins (SPs) have been studied in COPD patients as biomarkers of
      disease severity and as predictive factors of unfavorable outcomes. The aim of
      this exploratory study was to evaluate serum levels of SP-A, SP-B, SP-C, and SP-D
      in patients with COPD both during AECOPD and in stability and to test their
      possible associations with disease severity and with the development of new
      exacerbation events. 20 consecutive COPD patients hospitalized for AECOPD were
      included. Serum SP levels were measured on admission, at discharge, and on
      stability. SP-A levels were significantly lower both on admission and at
      discharge in patients with early relapse compared to those with late or no
      relapse (29.2 +/- 9.1 vs. 43.9 +/- 16.9 ng/ml, p = 0.037, and 24.3 +/- 2.8 vs.
      39.3 +/- 14.2 ng/ml, p = 0.011, respectively). SP-B levels were found to have a
      trend to be higher at discharge and significantly higher on stability in patients
      experiencing an early relapse compared to those with late or no relapse (52.5 +/-
      31.6 vs. 31.4 +/- 32.3 ng/ml, p = 0.052 and 64.8 +/- 32.6 vs. 32.8 +/- 25.6
      ng/ml, p = 0.024, respectively). Finally, the ROC analysis showed that serum SP
      A, SP-B, and SP-C levels at discharge, seemed to be significant predictors of
      early relapse. Our conclusion is that serum levels of SPs might be related to
      disease outcomes in COPD patients.

PMID- 29445935
TI  - Readmission Due to Exacerbation of COPD: Associated Factors.
AB  - OBJECTIVES: To compare characteristics of patients readmitted after discharge by
      chronic obstructive pulmonary disease (COPD) exacerbation with those who were not
      readmitted and to identify factors associated with readmission risk. PATIENTS AND
      METHODS: We randomly selected a group of 40 COPD patients with high frequency of
      readmissions (HFR), who had >= 2 admissions by COPD exacerbation within 30 days
      after the last admission in 2015, and another group of 40 COPD patients with low
      frequency of readmissions (LFR), with 0-1 admissions in that period. RESULTS:
      Patients of the HFR group, compared to those in LFR group, were more frequently
      males (p = 0.009), older (p = 0.022), had a higher degree of dyspnea (p = 0.044),
      worse lung function (p = 0.049), belonged more frequently to exacerbator
      emphysema phenotype (p < 0.001), and had a higher frequency of diabetes (p =
      0.049). The variables independently associated with increased risk of HFR were
      sex (OR 0.06, 95% CI 0.01-0.63, in women in relation to males), exacerbator
      emphysema phenotype (OR 28.61, 95% CI 3.59 compared to non-exacerbator
      phenotype), complications during hospitalization (OR 0.09, 95% CI 0.01-0.62,
      compared with those without complications), destabilized heart failure (OR 5.25,
      95% CI 1.11-24.75, compared to those who did not), and length of hospital stay
      (OR 0.79, 95% CI 0.65-0.95, per day). CONCLUSIONS: Chronic obstructive pulmonary
      disease patients with HFR are more frequently male, older, have worse dyspnea,
      lower lung function, belong more frequent to exacerbator emphysema phenotype, and
      more frequently diabetics. The variables that continued to be independent
      predictors of HFR in the multivariate analysis were sex, phenotype, occurrence of
      complications during admission, destabilized heart failure, and length of
      hospital stay.

PMID- 29445936
TI  - Pulmonary Arterial Hemodynamic Assessment by a Novel Index in Systemic Sclerosis
      Patients: Pulmonary Pulse Transit Time.
AB  - OBJECTIVES: Systemic sclerosis (SSc) is a chronic, inflammatory, and autoimmune
      connective tissue disease that is associated with vascular lesions, and fibrosis
      of the skin and visceral organs. Cardiac complications may occur as a secondary
      effect of SSc as a result of pulmonary arterial hypertension and interstitial
      lung disease. The objective of this study was to assess whether the pulmonary
      pulse transit time (pPTT) could serve as a diagnostic marker for pulmonary
      arterial alterations in patients with SSc, prior to development of pulmonary
      hypertension. METHODS: Twenty-five SSc patients as a study group and 25 age- and
      sex-matched healthy volunteers for the control group were recruited to the study.
      Right ventricle function parameters, such as tricuspid annular plane systolic
      excursion (TAPSE), estimated pulmonary artery systolic pressure (ePASP), right
      ventricular dimensions, right ventricle fractional area changes, and myocardial
      perfusion index (MPI) were measured and calculated. Pulmonary pulse transit time
      was defined as the time interval between the R-wave peak in the ECG and the
      corresponding peak late systolic pulmonary vein flow velocity. RESULTS: Right
      ventricle myocardial performance index (RVMPI) and eSPAP were significantly
      higher in the SSc group than the controls (p = 0.032, p = 0.012, respectively).
      Pulmonary pulse transit time and TAPSE was shorter in the patients with SSc (p =
      0.006, p = 0.015, respectively). In correlation analysis, pPTT was inversely
      correlated with RVMPI (r = - 0.435, p = 0.003), eSPAP (r = - 0.434, p = 0.003),
      and disease duration (r = - 0.595, p = 0.003). Conversely, it positively
      correlated with TAPSE (r = 0.345, p = 0.022). CONCLUSION: pPTT was found to be
      shorter in SSc patients. pPTT might serve as a surrogate marker of pulmonary
      hemodynamics in patients with SSc, even prior to the development of pulmonary
      hypertension.

PMID- 29445937
TI  - Secondary Hemophagocytic Syndrome Associated with COG6 Gene Defect: Report and
      Review.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disease
      that is characterized by proliferation and infiltration of hyperactivated
      macrophages and T-lymphocytes. Clinically, it is characterized by prolonged
      fever, hepatosplenomegaly, hypertriglyceridemia, hypofibrinogenemia,
      pancytopenia, and hemophagocytosis in the bone marrow, spleen, or lymph nodes. It
      can be classified as primary if it is due to a genetic defect, or secondary if it
      is due to a different etiology such as severe infection, immune deficiency
      syndrome, rheumatological disorder, malignancy, and inborn errors of metabolism
      such as galactosemia, multiple sulfatase deficiency, lysinuric protein
      intolerance, Gaucher disease, Niemann-Pick disease, Wolman disease, propionic
      acidemia, methylmalonic acidemia, biotinidase deficiency, cobalamin C defect,
      galactosialidosis, Pearson syndrome, and long-chain 3-hydroxyacyl-CoA
      dehydrogenase (LCHAD) deficiency. For the first time in the literature, we report
      on a 5-year-old girl diagnosed with a Component of Oligomeric Golgi Complex 6
      (COG6) gene defect complicated by HLH. Finally, we review the literature on
      inborn errors of metabolism associated with HLH and compare the previously
      reported patients of COG6 gene defect with our patient.

PMID- 29445938
TI  - Mental Health of Homeless Youth: Moderation by Peer Victimization and Teacher
      Support.
AB  - The link between youth homelessness and mental health functioning was examined
      using state population-representative 2015 Youth Risk Behavior Survey (YRBS)
      data. The moderating role of victimization and perceived teacher support also was
      examined. Consistent with hypotheses, results indicated that homelessness was
      associated with greater mental health challenges, more victimization, and less
      teacher support. The association between homelessness and mental health was not
      moderated by perceived teacher support. However, victimization experiences served
      as a moderator such that more victimization exacerbated the effect of
      homelessness on mental health challenges. This study supports the utility of the
      YRBS for gaining understanding of the experiences and needs of youth experiencing
      homelessness and adds to the growing literature on predictors of individual
      differences in mental health functioning of these vulnerable youth.

PMID- 29445939
TI  - A comparison of two models for breast cancer mortality for women with ductal
      carcinoma in situ: an SEER-based analysis.
AB  - BACKGROUND: Approximately 1% of patients with ductal carcinoma in situ (DCIS)
      will die of breast cancer within 10 years. Women who develop an invasive breast
      cancer after DCIS have a much greater risk of dying than those who do not and it
      is often stated that these deaths are a consequence of metastases from the
      invasive in-breast recurrence. This progression is the result of a two-step
      process: first local invasive recurrence and then spread beyond the breast. A
      large proportion of women who die of DCIS have no record of invasive recurrence.
      We used SEER data and a simulation approach to test whether the actual mortality
      data are consistent with the two-step model. METHODS: First, we constructed
      Kaplan-Meier mortality curves for all patients with pure DCIS and with small node
      negative invasive breast cancers in the Surveillance, Epidemiology and End
      Results (SEER) registries database (1998-2014). We then constructed, through
      simulation, theoretical breast cancer mortality curves. To model the two-step
      scenario, we applied the annual incidence rates of incident invasive cancer
      following DCIS and of death from invasive cancer after DCIS to a theoretical
      cohort of 100,000 women. RESULTS: The observed 15-year breast cancer-specific
      mortality rate for patients with pure DCIS in the SEER database was 2.0%. The
      expected mortality for DCIS patients (assuming a two-step process) was only 1.1%
      at 15 years. Assuming the mortality rates following DCIS were one-half of those
      observed for patients with small invasive breast cancers, the expected mortality
      at 15 years post-DCIS was 2.1%. CONCLUSIONS: In the SEER database, we observed
      far more deaths from DCIS than would be expected under a model where all deaths
      from breast cancer occur amongst women who experience an invasive local
      recurrence. This lends support to the hypothesis that DCIS mortality is not
      restricted to those women who experience an in-breast invasive cancer and that
      DCIS has properties similar to small invasive breast cancers.

PMID- 29445941
TI  - Population norms for the EQ-5D-3L: a cross-country analysis of population surveys
      for 20 countries.
AB  - This study provides EQ-5D population norms for 20 countries (N = 163,838), which
      can be used to compare profiles for patients with specific conditions with data
      for the average person in the general population in a similar age and/or gender
      group. Descriptive EQ-5D data are provided for the total population, by gender
      and by seven age groups. Provided index values are based on European VAS for all
      countries, based on TTO for 11 countries and based on VAS for 10 countries.
      Important differences exist in EQ-5D reported health status across countries
      after standardizing for population structure. Self-reported health according to
      all five dimensions and EQ VAS generally decreased with increasing age and was
      lower for females. Mean self-rated EQ VAS scores varied from 70.4 to 83.3 in the
      total population by country. The prior living standards (GDP per capita) in the
      countries studied are correlated most with the EQ VAS scores (0.58), while
      unemployment appeared to be significantly correlated in people over the age of 45
      only. A country's expenditure on health care correlated moderately with higher
      ratings on the EQ VAS (0.55). EQ-5D norms can be used as reference data to assess
      the burden of disease of patients with specific conditions. Such information, in
      turn, can inform policy-making and assist in setting priorities in health care.

PMID- 29445940
TI  - Differences in breast cancer incidence among young women aged 20-49 years by
      stage and tumor characteristics, age, race, and ethnicity, 2004-2013.
AB  - PURPOSE: Younger women diagnosed with breast cancer have poorer prognoses and
      higher mortality compared to older women. Young black women have higher incidence
      rates of breast cancer and more aggressive subtypes than women of other
      races/ethnicities. In this study, we examined recent trends and variations in
      breast cancer incidence among young women in the United States. METHODS: Using
      2004-2013 National Program of Cancer Registries and Surveillance, Epidemiology,
      and End Results Program data, we calculated breast cancer incidence rates and
      trends and examined variations in stage, grade, and tumor subtype by age and
      race/ethnicity among young women aged 20-49 years. RESULTS: The majority of
      breast cancer cases occurred in women aged 40-44 and 45-49 years (77.3%). Among
      women aged < 45 years, breast cancer incidence was highest among black women.
      Incidence trends increased from 2004 to 2013 for Asian or Pacific Islander (API)
      women and white women aged 20-34 years. Black, American Indian or Alaska Native,
      and Hispanic women had higher proportions of cases diagnosed at later stages than
      white and API women. Black women had a higher proportion of grade III-IV tumors
      than other racial/ethnic groups. Across all age groups, incidence rates for
      triple-negative breast cancer were significantly higher in black women than women
      of other races/ethnicities, and this disparity increased with age. CONCLUSIONS:
      Breast cancer among young women is a highly heterogeneous disease. Differences in
      tumor characteristics by age and race/ethnicity suggest opportunities for further
      research into personal and cultural factors that may influence breast cancer risk
      among younger women.

PMID- 29445942
TI  - Market structure and competition in the healthcare industry : Results from a
      transition economy.
AB  - The present paper provides first empirical evidence on the relationship between
      market size and the number of firms in the healthcare industry for a transition
      economy. We estimate market-size thresholds required to support different numbers
      of suppliers (firms) for three occupations in the healthcare industry in a large
      number of distinct geographic markets in Slovakia, taking into account the
      spatial interaction between local markets. The empirical analysis is carried out
      for three time periods (1995, 2001 and 2010) which characterise different stages
      of the transition process. Our results suggest that the relationship between
      market size and the number of firms differs both across industries and across
      periods. In particular, we find that pharmacies, as the only completely
      liberalised market in our dataset, experience the largest change in competitive
      behaviour during the transition process. Furthermore, we find evidence for
      correlation in entry decisions across administrative borders, suggesting that
      future market analysis should aim to capture these regional effects.

PMID- 29445944
TI  - Diagnosis and treatment of anti-myelin oligodendrocyte glycoprotein antibody
      positive optic neuritis.
AB  - Anti-myelin-oligodendrocyte glycoprotein (MOG) antibody positive optic neuritis
      has been established as a new subset of optic neuropathy. Anti-MOG antibodies are
      usually measured by cell-based assay. Patients with anti-MOG antibody positive
      optic neuritis respond well to steroid therapy, and, while visual acuity outcomes
      are favorable, significant visual field defects remain. Furthermore, patients who
      are anti-MOG antibody positive have higher rates of recurrence compared to
      antibody negative patients. Based on these findings, anti-MOG antibody positive
      patients with optic neuritis have the characteristics of good visual outcomes,
      residual visual field defects, and high risk of recurrence. Tests for anti-MOG
      antibody are useful for the diagnosis and treatment of optic neuritis.

PMID- 29445943
TI  - Impact of the clinical use of ROCK inhibitor on the pathogenesis and treatment of
      glaucoma.
AB  - Rho-associated protein kinase (ROCK), a ubiquitously expressed signaling
      messenger and downstream effector of Rho, is activated by several bioactive
      factors in the aqueous humor (AH). Rho-ROCK signaling regulates a wide spectrum
      of fundamental cellular events, including cell adhesion, motility, proliferation,
      differentiation, and apoptosis. Previous studies, including our own, found that
      ROCK inhibitor lowers intraocular pressure (IOP) via a direct effect on the
      conventional AH outflow pathway, by regulation of contractile properties,
      fibrotic activity, and permeability of the trabecular meshwork (TM) and Schlemm's
      canal (SC) tissues, influencing extracellular matrix (ECM) production. Recently,
      a novel ROCK inhibitor, ripasudil, has been introduced in Japan. Other ROCK
      inhibitors are now in clinical trials as new IOP-lowering drugs for glaucoma
      patients. To date, ripasudil, administered together with other glaucoma
      medications, has proved safe and efficient in lowering IOP as well as additional
      effects such as prostaglandin analogs, beta-blockers, and carbonic anhydrase
      inhibitors, all of which help lower IOP by different mechanisms. In addition, we
      found that long-term treatment with ripasudil exerted an additional IOP-lowering
      effect, especially in eyes with high IOP, suggesting that late-onset remodeling
      of the ECM in glaucomatous eyes may elicit mild and delayed changes in IOP
      levels. ROCK inhibitors have also shown several additional effects, including
      increased retinal blood flow, direct protection of neurons against various types
      of stress, and regulation of wound healing; these benefits may potentially be
      useful in glaucoma treatment.

PMID- 29445945
TI  - Spectral domain optical coherence tomography and fundus autofluorescence findings
      in cytomegalovirus retinitis in HIV-infected patients.
AB  - PURPOSE: To assess the usefulness of spectral domain optical coherence tomography
      (SD-OCT) and fundus autofluorescence (FAF) findings in cytomegalovirus (CMV)
      retinitis. STUDY DESIGN: Observational case series. METHODS: Thirteen eyes of 11
      human immunodeficiency virus (HIV)-positive patients with CMV retinitis underwent
      full ophthalmologic examinations, SD-OCT, and 4 eyes of 4 patients underwent FAF.
      FAF images included short-wavelength autofluorescence (SW-AF) and near-infrared
      autofluorescence (IR-AF). CMV retinitis was classified into proposed categories
      of acute, subacute, remission, and recurrent; the acute stage was further
      subdivided into initial, early, and late stages. RESULTS: In the initial stage,
      vertical structural disruption of all retinal layers was observed by SD-OCT, and
      FAF showed hyperautofluorescence on SW-AF and hypoautofluorescence on IR-AF. In
      the early stage, SD-OCT showed significant retinal thickening; cells and debris
      from the retinal surface to the vitreous; enlarged vessels with/without thickened
      vessel walls; and highly complicated serous retinal detachment. In the late to
      subacute stage, features observed included rhegmatogenous retinal detachment with
      shrinking posterior hyaloid membrane and waving from the ellipsoid zone to the
      retinal pigment epithelium. In remission, FAF findings were hypoautofluorescence
      on SW-AF and hyperautofluorescence on IR-AF. CONCLUSION: Although the number of
      examined eyes was limited, SD-OCT and FAF provide new information in various
      stages of CMV retinitis in patients with HIV infection that is not obtainable by
      conventional examination and which may be of great benefit when screening for the
      initial stage of CMV retinitis.

PMID- 29445946
TI  - Paravertebral tumours of the cervicothoracic junction extending into the
      mediastinum: surgical strategies in a no man's land.
AB  - PURPOSE: Cervicothoracic paravertebral neoplasms extending into the mediastinum
      pose a surgical challenge due the complex regional anatomy, their biological
      nature, rarity and surgeon's unfamiliarity with the region. We aim to define a
      surgical access framework addressing the aforementioned complexities whilst
      achieving oncological clearance. METHODS: We carried out a retrospective review
      of 28 consecutive patients operated in two tertiary referral centres between 1998
      and 2015. Pathology was located paravertebrally from C6 to T4 with superior
      mediastinum invasion. Patients were operated jointly by a spinal and a thoracic
      surgeon. RESULTS: Tumours were classified according to subclavian fossa
      involvement as anteromedial, anterolateral and posterior and according to
      histology in benign nerve sheath tumour group (n = 10) and malignant bone or soft
      tissue tumours (n = 18). Three surgical routes were utilised: (1) median
      sternotomy (n = 11), (2) anterior cervical transsternal approach (n = 7) and (3)
      high posterolateral thoracotomy (n = 10). Resection was en bloc with wide margins
      in 22 cases, marginally complete in 3 and incomplete in 3. Complications included
      Horner's syndrome (n = 3), infection (n = 2) and transient neurological deficit
      (n = 4). In the nerve sheath tumour group, no recurrence or reoperation took
      place with a median follow-up of 4.5 years. In the malignant bone and soft tissue
      group, 96% of the patients were alive at 1 year, 67% at 2 years and 33% at 5
      years. No vascular injuries or operative related deaths were observed.
      CONCLUSIONS: Classification of cervicothoracic paravertebral neoplasms with
      mediastinal extension according to the relationship with the subclavicular fossa
      and dual speciality involvement allows for a structured surgical approach and
      provides minimal morbidity/maximum resection and satisfactory oncological
      outcomes. These slides can be retrieved under Electronic Supplementary Material.

PMID- 29445947
TI  - Bone graft materials for posterolateral fusion made simple: a systematic review.
AB  - BACKGROUND: Iliac crest has long been the gold standard for lumbar fusion, but
      concerns over donor site morbidity have led to a wide variety of bone graft
      substitutes. Despite prolific research, a general consensus is yet to be reached
      on bone graft materials that lead to optimal fusion. PURPOSE: The purpose of this
      review is to evaluate the current literature for bone graft material options that
      maximize fusion rate in posterolateral lumbar fusion surgery. DESIGN: Systematic
      Review. METHODS: A PRISMA-compliant systematic review of PubMed, EMBASE, and the
      Web of Science was conducted. Included studies were published from January 2000
      to July 2015, were clinical human research studies involving available autograft,
      allograft, or synthetic bone graft options in posterolateral lumbar spine fusion,
      and reported radiographic fusion rate as a primary end outcome. This research had
      no funding source and the authors have no conflicts to declare. RESULTS: 81
      articles underwent full-text review, and 48 were included in this study. 18
      studies assessed fusion rate by plain radiographs alone (37.5%), while 6 used CT
      scan (12.5%), and 24 used both (50.0%). 45 studies looked at ICBG in conjunction
      with LAG (29), BCP(1), APC (2), BMPs (6), or DBM (1). Aggregate mean fusion rates
      among these ranged from 68.0 to 91.5%. 22 studies evaluated fusion rates of LAG,
      either isolated (3) or combined with ceramic extenders (8), DBM (4), BMP (1), BMA
      (4), APC (1), or ICBG(1). Aggregate mean fusion rate ranged from 75 to 95.5%.
      With the exception of studies involving allograft (mean fusion rate 40.0%), the
      mean fusion rate for all other graft combinations exceeded 70.0%. CONCLUSIONS:
      While our results find that LAG+BMA provided highest fusion rate, most material
      options analyzed in this study provide comparable fusion outcomes. The ideal
      graft option must incorporate a combination of materials with osteoconductive,
      osteoinductive, and osteogenic properties. Our results represent the robust and
      dynamic nature of the current state of lumbar graft technology. These slides can
      be retrieved under Electronic Supplementary Material.

PMID- 29445948
TI  - Intraspinal neural axis abnormalities in severe spinal deformity: a 10-year MRI
      review.
AB  - PURPOSE: Documents indicated that the average prevalence of intraspinal neural
      axis abnormalities (INAAs) in presumed idiopathic scoliosis (PIS) patients was
      about 17.7%. However, paucity study focuses on the incidence of INAAs in severe
      spinal deformity (SSDs). In this study, we investigate the incidence of
      intraspinal neural axis abnormalities (IINAAs) and the clinical relevance in SSD
      at a single center. METHODS: All the patients with SSDs admitted for spinal
      surgery were evaluated from 2003 to 2014. INCLUSION CRITERIA: patients who
      present with coronal Cobb over 90 degrees  (and/or the sagittal Cobb >= 90
      degrees ); patients with whole spine magnetic resonance imaging (MRI) done
      preoperatively; and patients with documented clinical findings preoperatively.
      EXCLUSION CRITERIA: ankylosing spondylitis, adult onset scoliosis, scoliosis
      secondary to bone destruction, and spinal dysraphism. RESULTS: 101 patients
      fulfilled the criteria were included. 43 patients were detected with INAAs
      (42.6%, 43/101). The most common INAAs was syrinx (S) (16/43, 37.2%). Of which,
      43.7% (7/16), 37.5% (6/16), and 18.7% (3/16) were spindle, slit, and swelling
      types, respectively. Most of them were located in thoracic (6/16, 37.5%) and
      cervical (5/16, 31.3%) region. MRI revealed Chiari malformation with
      syringomyelia (C + S) in ten patients (10/43, 23.2%), Chiari malformation (C) in
      6 patients (6/43, 13.9%) and others in 11 patients (11/43, 25.6%). As to the
      etiology, most patients with INAAs were PIS (34/43, 79.1%). On clinical
      examination, 16 of 101 patients (16/101, 15.8%) had abnormal neurologic signs. 15
      of 16 patients (15/16, 93.7%) with abnormal neurologic signs had INAAs on MRI. On
      the other hand, 28 of 43 patients (28/43, 65.1%) with INAAs on MRI presented
      neurologically intact. 28 of 85 patients (28/85, 32.9%) with neurologically
      intact were detected with INAAs on MRI. CONCLUSION: The incidence of INAAs in
      SSDs was 42.6%. 65.1% of them present intact neurologic status. The most common
      neural anomaly was syrinx. Preoperative whole spine MRI must be beneficial for
      SSDs even in the absence of neurological findings. These slides can be retrieved
      under Electronic Supplementary Material.

PMID- 29445949
TI  - Postoperative K-line conversion from negative to positive is independently
      associated with a better surgical outcome after posterior decompression with
      instrumented fusion for K-line negative cervical ossification of the posterior
      ligament.
AB  - PURPOSE: Addition of posterior instrumented fusion to laminoplasty (posterior
      decompression with instrumented fusion: PDF) can improve the surgical outcome of
      patients with K-line (-) cervical ossification of the longitudinal ligament
      (OPLL) compared with laminoplasty alone. We sought to elucidate the factors that
      are significantly associated with a better outcome after PDF for K-line (-) OPLL.
      METHODS: The present study included 38 patients who underwent PDF for K-line (-)
      OPLL and were followed up for at least 1 year after surgery. Clinical outcome was
      assessed using Japanese Orthopedic Association (JOA) scores for cervical
      myelopathy and the recovery rate was calculated. Patients who belonged to the
      upper quartile of all the patients according to rank order of the JOA score
      recovery rate were considered to have a good outcome. The correlations between
      good outcome, patient factors and imaging assessments were analyzed
      statistically. RESULTS: Univariate analyses showed that postoperative conversion
      of K-line from (-) to (+) (p = 0.004), no increase in the sagittal vertical axis
      from the center of gravity of the head to C7 (p = 0.07), and a lower grade of
      preoperative intramedullary T2-signal intensity (p = 0.03) were candidates for
      the association. Stepwise logistic regression analysis revealed that
      postoperative K-line conversion from (-) to (+) is an independent factor that is
      significantly associated with a better surgical outcome (p = 0.04). CONCLUSION:
      Postoperative K-line conversion from (-) to (+) is a factor independently
      associated with a better surgical outcome. These slides can be retrieved under
      Electronic Supplementary material.

PMID- 29445950
TI  - The importance of proximal femoral angle on sagittal balance and quality of life
      in children and adolescents with high-grade lumbosacral spondylolisthesis.
AB  - PURPOSE: Previous studies did not specifically assess the influence of proximal
      femoral angle (PFA) on sagittal balance in high-grade spondylolisthesis (HGS). In
      addition, the relationship between PFA and quality of life (QOL) remains unknown.
      This study determines if increased PFA is associated with decreased QOL and
      sagittal balance in lumbosacral HGS. METHODS: This retrospective case-control
      study was performed on a cohort of 56 normal subjects and 42 patients with HGS.
      Initially, PFA was measured twice by 3 raters in a random subset of 30 subjects
      (15 normal and 15 HGS) to determine the intrarater and interrater reliability of
      the measurement technique. PFA was then measured for all subjects. For the 42
      patients with HGS, QOL was assessed from the SRS-22 questionnaire, in addition to
      the evaluation of the spino-pelvic balance. RESULTS: The intrarater and
      interrater intraclass correlation coefficients for the measurement of PFA were,
      respectively, 0.951 and 0.958, suggesting excellent reliability. PFA was
      significantly higher in HGS patients (8.3 degrees  +/- 6.7 degrees ; range - 5
      degrees  to 24 degrees ) when compared to normal subjects (3.0 degrees  +/- 3.1
      degrees ; range - 6 degrees  to 10 degrees ). The PFA in HGS was 5.6 degrees  +/-
      5.6 degrees  (range - 5 degrees  to 18 degrees ), 8.9 degrees  +/- 6.7 degrees 
      (range - 2 degrees  to 24 degrees ), and 14.0 degrees  +/- 6.0 degrees  (range 7
      degrees -23 degrees ) in type 4 (balanced pelvis), type 5 (unbalanced
      pelvis/balanced spine), and type 6 (unbalanced pelvis and spine) subjects,
      respectively. There were, respectively, 23.5% (4/17), 26.3% (5/19), and 83.3%
      (5/6) of HGS patients with abnormal PFA >= 10 degrees  in type 4, type 5, and
      type 6 subgroups. Increased PFA in HGS patients was related with deteriorating
      self-image, pain, function and total SRS-22 score, as well as with increasing
      pelvic tilt and decreasing sacral slope. CONCLUSION: A PFA >= 10 degrees  is
      proposed as a criterion to define abnormal PFA. PFA was increased in HGS and
      increased along with deteriorating sagittal balance and QOL. PFA is a clinically
      relevant parameter of sagittal balance, and can be useful in the evaluation and
      management of patients with HGS.

PMID- 29445951
TI  - Full endoscopic lumbar interbody fusion (FELIF): technical note.
AB  - PURPOSE: Interbody fusion by open discectomy is the usual treatment for
      degenerative lumbar disease but requires a relatively long recovery period.
      Prevalent several interbody fusion methods have shown limitations by its own
      character. Full endoscopic lumbar interbody fusion (FELIF) has advantages in
      direct decompression of pathology with minimal invasive technique. We report
      novel technique of endoscopic fusion method through full guided with endoscopic
      view monitoring system. METHODS: The authors provide an introduction of FELIF
      technique followed by a description of the technical steps with discussion on its
      indications and advantages. In particular, tips to shorten operation time,
      simplify technical steps, and avoid complications are also presented.
      CONCLUSIONS: FELIF is a safe and effective interbody fusion option to decompress
      the lumbar exiting nerve root and ventral side of dura directly with minimal
      invasive situation. These slides can be retrieved under Electronic Supplementary
      Material.

PMID- 29445952
TI  - (a,k)-Anonymous Scheme for Privacy-Preserving Data Collection in IoT-based
      Healthcare Services Systems.
AB  - The widely use of IoT technologies in healthcare services has pushed forward
      medical intelligence level of services. However, it also brings potential privacy
      threat to the data collection. In healthcare services system, health and medical
      data that contains privacy information are often transmitted among networks, and
      such privacy information should be protected. Therefore, there is a need for
      privacy-preserving data collection (PPDC) scheme to protect clients (patients)
      data. We adopt (a,k)-anonymity model as privacy pretection scheme for data
      collection, and propose a novel anonymity-based PPDC method for healthcare
      services in this paper. The threat model is analyzed in the client-server-to-user
      (CS2U) model. On client-side, we utilize (a,k)-anonymity notion to generate
      anonymous tuples which can resist possible attack, and adopt a bottom-up
      clustering method to create clusters that satisfy a base privacy level of (a1,k1)
      anonymity. On server-side, we reduce the communication cost through
      generalization technology, and compress (a1,k1)-anonymous data through an UPGMA
      based cluster combination method to make the data meet the deeper level of
      privacy (a2,k2)-anonymity (a1 >= a2, k2 >= k1). Theoretical analysis and
      experimental results prove that our scheme is effective in privacy-preserving and
      data quality.

PMID- 29445953
TI  - Competition between abiogenic Al3+ and native Mg2+, Fe2+ and Zn2+ ions in protein
      binding sites: implications for aluminum toxicity.
AB  - Abiogenic aluminum has been implicated in some health disorders in humans.
      Protein binding sites containing essential metals (mostly magnesium) have been
      detected as targets for the "alien" Al3+. However, the acute toxicity of aluminum
      is very low. Although a substantial body of information has been accumulated on
      the biochemistry of aluminum, the underlying mechanisms of its toxicity are still
      not fully understood. Several outstanding questions remain unanswered: (1) Why is
      the toxicity of aluminum, unlike that of other "alien" metal cations, relatively
      low? (2) Apart from Mg2+ active centers in proteins, how vulnerable are other
      essential metal binding sites to Al3+ attack? (3) Generally, what factors do
      govern the competition between 'alien" Al3+ and cognate divalent metal cations in
      metalloproteins under physiologically relevant conditions? Here, we endeavor to
      answer these questions by studying the thermodynamic outcome of the competition
      between Al3+ and a series of biogenic metal cations, such as Mg2+, Fe2+ and Zn2+,
      in model protein binding sites of various structures, compositions, solvent
      exposure and charge states. Density functional theory calculations were employed
      in combination with polarizable continuum model computations. For the first time,
      the presence of different Al3+ soluble species at physiological pH was properly
      modeled in accordance with experimental observations. The results suggest that a
      combination of concentration and physicochemical factors renders the Al3+ -> M2+
      (M = Mg, Fe, Zn) substitution and subsequent metalloenzyme inhibition a low
      occurrence event at ambient pH: the more active aluminum species, [Al(H2O)6]3+,
      presents in very minute quantities at physiological conditions, while the more
      abundant soluble aluminum hydrate, {[Al(OH-)4](H2O)2}-, appears to be
      thermodynamically incapable of substituting for the native cation.

PMID- 29445954
TI  - Normal boundary intersection applied as multivariate and multiobjective
      optimization in the treatment of amoxicillin synthetic solution.
AB  - Amoxicillin is a useful antibiotic to combat bacterial infections. However, this
      drug can cause serious problems when discarded in waterways due to its great
      bioaccumulation potential. This compound can be treated via advanced oxidation
      processes (AOPs), which are capable of converting amoxicillin into carbon dioxide
      and water. In this context, the use of ozone as an oxidizer has excelled in
      amoxicillin degradation. This paper aims at treating a synthetic solution of
      amoxicillin (0.1 g L-1) in a reactor with ozone bubbling. A Design of Experiment
      (DoE) with a response surface known as Central Composite Design (CCD) was used to
      optimize the treatment process. In addition, a Normal Boundary Intersection (NBI)
      method was used in the construction of a Pareto boundary chart. Results after 1-h
      treatment showed a reduction of 53% of the initial organic matter from a designed
      model using factors, such as pH, ozone generator power, and O3 flow. A model was
      built from the CCD with score of 0.9929. Thus, the model was able to represent
      the real scenario with confidence.

PMID- 29445955
TI  - Fifty shades of white: how white feather brightness differs among species.
AB  - White colouration is a common and important component of animal visual signalling
      and camouflage, but how and why it varies across species is poorly understood.
      White is produced by wavelength-independent and diffuse scattering of light by
      the internal structures of materials, where the degree of brightness is related
      to the amount of light scattered. Here, we investigated the morphological basis
      of brightness differences among unpigmented pennaceous regions of white body
      feathers across 61 bird species. Using phylogenetically controlled comparisons of
      reflectance and morphometric measurements, we show that brighter white feathers
      had larger and internally more complex barbs than duller white feathers. Higher
      brightness was also associated with more closely packed barbs and barbules,
      thicker and longer barbules, and rounder and less hollow barbs. Larger species
      tended to have brighter white feathers than smaller species because they had
      thicker and more complex barbs, but aquatic species were not significantly
      brighter than terrestrial species. As similar light scattering principals affect
      the brightness of chromatic signals, not just white colours, these findings help
      broaden our general understanding of the mechanisms that affect plumage
      brightness. Future studies should examine how feather layering on a bird's body
      contributes to differences between brightness of white plumage patches within and
      across species.

PMID- 29445956
TI  - High Performance of PEDOT:PSS/n-Si Solar Cells Based on Textured Surface with
      AgNWs Electrodes.
AB  - Hybrid heterojunction solar cells (HHSCs) have gained extensive research and
      attention due to simple device structure and low-cost technological processes.
      Here, HHSCs are presented based on a highly transparent conductive polymer
      poly(3,4ethylenedioxythiophene):poly(styrenesulfonate)(PEDOT:PSS) directly spin
      coated on an n-type crystalline silicon with microscale surface textures, which
      are prepared by traditional chemical etching. We have studied interface
      properties between PEDOT:PSS and textured n-Si by varying coating conditions.
      Final power conversion efficiency (PCE) could arrive at 8.54% by these simple
      solution-based fabrication processes. The high conversion efficiency is
      attributed to the fully conformal contact between PEDOT:PSS film and textured
      silicon. Furthermore, the reflectance of the PEDOT:PSS layer on textured surface
      is analyzed by changing film thickness. In order to improve the performance of
      the device, silver nanowires were employed as electrodes because of its better
      optical transmittance and electrical conductivity. The highest PCE of 11.07% was
      achieved which displayed a 29.6% enhancement compared with traditional silver
      electrodes. These findings imply that the combination of PEDOT:PSS film and
      silver nanowire transparent electrodes pave a promising way for realizing high
      efficiency and low-cost solar cells.

PMID- 29445958
TI  - Histopathological and Behavioral Assessments of Aging Effects on Stem Cell
      Transplants in an Experimental Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) displays cognitive and motor symptoms following the
      initial injury which can be exacerbated by secondary cell death. Aging
      contributes significantly to the morbidity of TBI, with higher rates of negative
      neurological and behaviors outcomes. In the recent study, young and aged animals
      were injected intravenously with human adipose-derived mesenchymal stem cells
      (hADSCs) (Tx), conditioned media (CM), or vehicle (unconditioned media) following
      TBI. The beneficial effects of hADSCs were analyzed using various molecular and
      behavioral techniques. More specially, DiR-labeled hADSCs were used to observe
      the biodistribution of the transplanted cells. In addition, a battery of behavior
      tests was conducted to evaluate the neuromotor function for each treatment group
      and various regions of the brain were analyzed utilizing Nissl, hematoxylin and
      eosin (H&E), and human nuclei (HuNu) staining. Finally, flow cytometry was also
      performed to determine the levels of various proteins in the spleen. Here, we
      discuss the protocols for characterizing the histopathological and behavioral
      effects of transplanted stem cells in an animal model of TBI, with an emphasis on
      the role of aging in the therapeutic outcomes.

PMID- 29445957
TI  - Treating Immune-Related Epilepsy.
AB  - PURPOSE OF REVIEW: This review explores different treatment modalities for immune
      mediated epilepsy, including epilepsy caused by autoantibodies as well as
      epilepsy in the context of systemic autoimmune disease. RECENT FINDINGS:
      Autoimmune epilepsy is an increasingly recognized entity. Conventional treatments
      for epilepsy, such as antiseizure medications and epilepsy surgery, are less
      successful in treating epilepsy caused by autoimmune disease. Immunomodulatory
      therapies such as corticosteroids, intravenous immunoglobulin, and plasma
      exchange are generally more successful in treating immune-mediated epilepsy than
      conventional epilepsy therapies. Autoimmune epilepsy should be considered as a
      possible etiology for patients with frequent seizures of unknown etiology. The
      response to immunotherapies is often promising, particularly in patients with
      antibodies to neuronal cell surface antigens.

PMID- 29445959
TI  - Methods for Monitoring Autophagy in Silkworm Organs.
AB  - In holometabolous insects, various larval organs are remodeled by autophagy
      during metamorphosis. Although moths and butterflies are among the first animal
      models in which this self-eating process was described, only in recent years
      autophagy has been analyzed in detail in these insects. In particular, the
      silkworm Bombyx mori, which represents a well-studied model among Lepidoptera,
      provides a wide repertoire of cellular and molecular tools useful for studying
      the occurrence of autophagy and for evaluating its role in postembryonic
      development. Here, we describe some morphological, biochemical, and molecular
      methods to monitor autophagy in silkworm organs.

PMID- 29445960
TI  - Is percutaneous kyphoplasty the better choice for minimally invasive treatment of
      neurologically intact osteoporotic Kummell's disease? A comparison of two
      minimally invasive procedures.
AB  - PURPOSE: The purpose of this study was to compare and evaluate the safety and
      efficacy of percutaneous vertebroplasty at a hyperextension position (PVPHP) and
      percutaneous kyphoplasty at a hyperextension position (PKPHP) for the treatment
      of osteoporotic Kummell's disease. METHODS: This study was a retrospective,
      single-centre study. There were 35 patients with osteoporotic Kummell's disease
      who were analyzed. Twenty-two of them underwent PVPHP and the other 13 patients
      underwent PKPHP from January 2013 to January 2015. The volume of bone cement
      injection and operation costs were compared. We compared the visual analogue
      score (VAS) and vertebral Cobb's angle at pre-operation, the second day after
      operation, and the final follow-up. We compared the Oswestry disability index
      (ODI) score at the pre-operation and the final follow-up. RESULTS: There were no
      significant differences in gender, age, course of disease, bone mineral density
      (BMD), and mean follow-up time between the two groups (P > 0.05). Regarding the
      costs of the operation, the PKPHP group was significantly higher than the PVPHP
      group (P < 0.05). Compared with the pre-operation (P < 0.05), the post-operative
      ODI score, VAS, and Cobb's angle of the two groups were improved significantly.
      Even though the correction of Cobb's angle in the PKPHP group was slightly better
      than the PVPHP position group, there were no significant differences between two
      groups (P > 0.05). At the final follow-up, the Cobb's angle was increased in both
      groups, but there was no significant difference (P > 0.05). There was no
      significant difference in the bone cement leakage rate between the two groups (P
      > 0.05). CONCLUSION: For the treatment of Kummell's disease, PVPHP and PKPHP are
      both safe and effective, but PVPHP is more economical and can be considered a
      preferred method of treatment.

PMID- 29445961
TI  - Application of combined porous tantalum scaffolds loaded with bone morphogenetic
      protein 7 to repair of osteochondral defect in rabbits.
AB  - PURPOSE: Porous tantalum (PT) has been widely used in orthopaedic applications
      for low modulus of elasticity, excellent biocompatibility, and the
      microstructures similar to cancellous bone. In order to improve the biological
      activity of PT, biologically active factors can be combined with the material.
      The purpose of this study was to investigate if bone morphogenetic protein 7 (BMP
      7) modifications could enhance the repairing of cartilage of PT in osteochondral
      defect in medial femoral condyle of rabbits. METHODS: A cylindrical osteochondral
      defect model was created on the animal medial femoral condyle of and filled as
      follows: PT modified with BMP-7 for MPT group, non-modified PT for the PT group,
      while no implants were used for the blank group. The regenerated osteochondral
      tissue was assessed and analyzed by histological observations at four, eight and
      16 weeks post-operation and evaluated in an independent and blinded manner by
      five different observers using a histological score. Osteochondral and
      subchondral bone defect repair was assessed by micro-CT scan at 16 weeks post
      operation, while the biomechanical test was performed at 16 weeks post-operation.
      RESULTS: Briefly, higher overall histological score was observed in the MPT group
      compared to PT group. Furthermore, more new osteochondral tissue and bone formed
      at the interface and inside the inner pores of scaffolds of the MPT group
      compared to PT group. Additionally, the micro-CT data suggested that the new bone
      volume fractions and the quantity and quality of trabecular bone, as well as the
      maximum release force of the bone, were higher in the MPT group compared to PT
      group. CONCLUSIONS: We demonstrated that the applied modified PT with BMP-7
      promotes excellent subchondral bone regeneration and may serve as a novel
      approach for osteochondral defects repair.

PMID- 29445962
TI  - Impact of surgical case order on peri-operative outcomes for total joint
      arthroplasty.
AB  - INTRODUCTION: There is growing support in the literatures that peri-operative
      outcomes are adversely affected by surgical case order in some certain surgical
      procedures. This study aimed to examine if similar phenomenon is also shared in
      total joint arthroplasty (TJA). METHODS: A total of 6548 joints (5183 patients)
      treated with primary TJA by a total of five surgeons at our institution from
      December 2011 to December 2015 were retrospectively reviewed in this study.
      Demographic data, operative duration, blood loss, peri-operative adverse events,
      medical cost, and length of hospital stay were collected and analyzed. Logistic
      regression was used to determine risk factors for adverse events. RESULTS: Of the
      6548 cases in this cohort, 1643 TJAs were classified as first round cases, 1744
      TJAs were second round cases, 1600 TJAs were third round cases, and 1561 TJAs
      were fourth or later round cases. Mean operating time was shorter in the
      intermediate cases (45.0 vs. 41.0 vs. 41.8 vs. 54.1 min, P < 0.01). Peri
      operative arthroplastic adverse events were increased in later surgical cases
      (2.07% vs. 2.18% vs. 3.06% vs. 4.87%, P < 0.01). Later case order (OR = 1.40 [95%
      CI: 1.22-1.61], P < 0.01) was a significant risk factor of arthroplastic adverse
      events. Patients undergoing TJA later in the day were more likely to have longer
      length of stay and higher cost than earlier cases. Peri-operative systemic
      complications and blood loss did not significantly differ between groups.
      CONCLUSION: Surgical case order is an independent risk factor for arthroplastic
      adverse events in TJA. TJA procedures performed later in the day have a higher
      risk for arthroplastic adverse events, but not for systematic adverse events.
      Significantly increased operative time, higher cost, and longer LOS were noted
      for fourth or later TJA cases. Data in our study reveals that performing more
      than three TJAs within a single day may imply compromised outcomes.

PMID- 29445963
TI  - Incomplete pure sensory stroke due to a pontine lacune.

PMID- 29445964
TI  - Different Methods for Modelling Severe Hypoglycaemic Events: Implications for
      Effectiveness, Costs and Health Utilities.
AB  - BACKGROUND: Clinical trials report severe hypoglycaemic events as the number of
      patients with at least one event out of the total randomised or number of events
      for a given total exposure. Different network meta-analysis models have been used
      to analyse these different data types. OBJECTIVE: This aim of this article was to
      establish the impact of using the different models on effectiveness, costs and
      health utility estimates. METHODS: We analysed a dataset used in a recent network
      meta-analysis of severe hypoglycaemic events conducted to inform National
      Institute for Health and Care Excellence recommendations regarding basal insulin
      choice for patients with type 1 diabetes mellitus. We fitted a model with a
      binomial likelihood reporting odds ratios (using a logit link) or hazard ratios
      (complementary log-log link), a model with a Poisson likelihood reporting hazard
      ratios and a shared-parameter model combining different types of data. We
      compared the results in terms of relative effects and resulting cost and
      disutility estimates. RESULTS: Relative treatment effects are similar regardless
      of which model or scale is used. Differences were seen in the probability of
      having an event on the baseline treatment with the logit model giving a baseline
      probability of 0.07, the complementary log-log 0.17 and the Poisson 0.29. These
      translate into differences of up to L110 in the yearly cost of a hypoglycaemic
      event and 0.004 in disutility. CONCLUSION: While choice of network meta-analysis
      model does not have a meaningful impact on relative effects for this outcome,
      care should be taken to ensure that the baseline probabilities used in an
      economic model are accurate to avoid misrepresenting costs and effects.

PMID- 29445965
TI  - Traumatic subarachnoid hemorrhage related to ophthalmic artery avulsion: a case
      report.
AB  - We present a case of ophthalmic artery (OA) traumatic avulsion, leading to a post
      traumatic subarachnoid hemorrhage (SAH) with ventricular blood invasion and
      hydrocephalus, mimicking an internal carotid aneurysm rupture. This is the third
      case of such an event reported in literature and the first without orbital
      fractures and optic nerve avulsion. Conservative treatment was sufficient for the
      avulsion, but surgery was needed for the coexisting eye luxation. Traumatic OA
      avulsion is a rare but possible event and should be suspected in case of basal
      cisterns SAH, evidence of orbital trauma and CT angiogram or angiographic absence
      of opacification of the OA.

PMID- 29445966
TI  - Thoracic ossification of ligamentum flavum manifesting holocord syringomyelia:
      case report.
AB  - It has been reported that syringomyelia is rarely associated with degenerative
      spinal disorders, but the case of holocord syringomyelia is never reported. We
      here present a case of a 59-year-old woman with right shoulder pain, dysesthesia
      of the right hand, and gait disturbance. Radiographically, examinations of the
      spine demonstrated holocord syringomyelia with ossification of ligamentum flavum
      at T2/3 level. Holocord syringomyelia was reduced remarkably after posterior
      decompression at the T2/3 level, and her symptoms also improved. We speculated
      that holocord syringomyelia might have developed due to craniospinal pressure
      dissociation caused by focal compression of dural sac from extradural
      degenerative change.

PMID- 29445967
TI  - The use of free nonvascularized fibular graft in the induced membrane technique
      to manage post-traumatic bone defects.
AB  - PURPOSE: The aim of the present study is to assess the results of free
      nonvascularized fibular graft in the induced membrane technique to manage bone
      defects. MATERIALS AND METHODS: Fifteen patients with segmental skeletal defects
      were treated by the induced membrane technique using free nonvascularized fibular
      graft. The ages ranged from 20 to 48 years with an average of 32 years. The cause
      of the defects was post-traumatic bone loss in all cases. The defects were
      located in the distal femur in nine cases, proximal tibia in two cases and middle
      third of the tibia in four cases. The defects ranged from 5 to 14 cm with an
      average of 8 cm. All cases were treated by the induced membrane technique in two
      stages. Autogenous cancellous bone graft and free nonvascularized fibular graft
      were used to fill the defect in the second stage of surgery. RESULTS: All cases
      healed without additional procedures after the second stage except in two cases.
      The time-to-bone union ranged from 4 to 13 months with an average of 7 months.
      After physiotherapy, all cases regained good range of ankle and knee movements
      except two cases. The complications included nonunion of the graft in two cases,
      deep wound infection in one case, and chronic pain along the iliac crest in one
      case. No cases were complicated by implant failure or refracture. CONCLUSION: The
      use of free nonvascularised fibular graft in the induced membrane technique
      reduces the time of healing and improves the final outcome.

PMID- 29445968
TI  - Arthroscopic direct meniscal extrusion reduction: surgical tips to reduce
      persistent meniscal extrusion in meniscal root repair.
AB  - Meniscal extrusion (ME) is defined as extension of the meniscal margin by at
      least 3 mm beyond the tibial margin. The main purpose of meniscal root repair is
      to restore the anatomy and function of the meniscus. Therefore, the reduction in
      the ME is one of the important objective outcomes. Nevertheless, the reduced
      meniscal extrusion was obtained in limited patients after meniscal root repair.
      This technical note described the arthroscopic direct meniscal extrusion
      reduction as surgical tips to reduce persistent meniscal extrusion in posterior
      meniscal root repair.

PMID- 29445970
TI  - Flower palate ultrastructure of the carnivorous plant Genlisea hispidula Stapf
      with remarks on the structure and function of the palate in the subgenus Genlisea
      (Lentibulariaceae).
AB  - In the genus Genlisea as well as in its sister genus Utricularia, the palate
      probably plays a key role in providing the colour, mechanical and olfactory
      stimuli to attract insect pollinators and to guide them to the generative
      structures and the nectary spur. However, information about the micro-morphology
      of the palate of Genlisea is scarce. This study aims to examine the structure of
      the palate in Genlisea hispidula in detail as well as the palate from other five
      species from the subgenus Genlisea. In particular, its aim is to ascertain
      whether these palates function as an area for the osmophores in the flower or
      whether they produce nectar. We showed that the palate in all of the species that
      were examined was the glandular type and that it had capitate, glandular
      trichomes, which had a similar general architecture across the species that were
      examined. No nectar secretion was observed on the palates. The ultrastructure of
      the palate trichomes showed that the palate glandular trichomes most probably
      function as scent glands that produce an olfactory stimulus for flower
      pollinators.

PMID- 29445969
TI  - The best cited articles of the European Journal of Orthopaedic Surgery and
      Traumatology (EJOST): a bibliometric analysis.
AB  - European Journal of Orthopaedic Surgery and Traumatology (EJOST) was founded in
      1991. It was initially named as Orthopedie-Traumatologie, and since then it is
      dedicated in sharing knowledge and new evidence in the field of orthopaedics.
      Within 28 volumes and 157 issues, it has published 3218 scientific articles. In
      the early years of its distribution, published articles were in French, while the
      last two decades EJOST only hosts English articles between its pages. By the very
      beginning of its launch, it has been publishing high-quality research articles in
      all orthopaedic subspecialties and has gradually become one of the leading
      journals in its specific subject area. The aim of this study was to identify,
      analyse and categorize the most frequently cited articles, published by EJOST
      since its launch.

PMID- 29445971
TI  - Progesterone PLGA/mPEG-PLGA Hybrid Nanoparticle Sustained-Release System by
      Intramuscular Injection.
AB  - PURPOSE: To prepare sustained-release PLGA/mPEG-PLGA hybrid nanoparticles of
      progesterone (PRG), and evaluate the descending required administration dosage in
      vivo. METHODS: PRG hybrid nanoparticles (PRG H-NPs) based on PLGA/mPEG-PLGA were
      compared with PRG nanoparticles (PRG-NPs) of pure PLGA as the matrix and PRG-oil
      solutions. Nanoparticles (NPs) were formed by the method of nanoemulsion, and the
      pharmacokinetics of the sustained-release PRG H-NPs in male Sprague dawley (SD)
      rats were investigated. The rats were randomly divided into four groups, each
      group received: single dose of PRG H-NPs (14.58 mg/kg, i.m.) and PRG-NPs (14.58
      mg/kg, i.m.), repeated dosing for 7 days of PRG-oil (2.08 mg/kg, i.m.) solution
      (Oil-L) and a higher dosage of PRG-oil (6.24 mg/kg, i.m.) solution (Oil-H),
      respectively. RESULTS: In the pharmacokinetic test, the PRG H-NPs exhibited a
      comparatively good sustained-release effect against the PRG-NPs without mPEG-PLGA
      and PRG-oil solution. The pharmacokinetic parameters of the PRG H-NPs, PRG-NPs,
      Oil-L and Oil-H were AUC0-t(ng.h.mL-1) 8762.1, 1546.1, 1914.5, and 12,138.9, t1/2
      (h)52.7, 44.1, 8.4 and 44.6 respectively. CONCLUSIONS: Owing to the modification
      of PEG, PRG H-NPs can act as safe delivery platforms for sustained-release of
      drugs with a lower dosage required.

PMID- 29445972
TI  - Design and validation of an osteochondral bioreactor for the screening of
      treatments for osteoarthritis.
AB  - Bioreactors are systems that can be used to monitor the response of tissues and
      cells to candidate drugs. Building on the experience developed in the creation of
      an osteochondral bioreactor, we have designed a new 3D printed system, which
      allows optical access to the cells throughout testing for in line monitoring.
      Because of the use of 3D printing, the fluidics could be developed in the third
      dimension, thus maintaining the footprint of a single well of a typical 96 well
      plate. This new design was optimized to achieve the maximum fluid transport
      through the central chamber, which corresponds to optimal nutrient or drug
      exposure. This optimization was achieved by altering each dimension of the
      bioreactor fluid path. A physical model for optimized drug exposure was then
      created and tested.

PMID- 29445973
TI  - Is heart rate response a reliable marker of adenosine-induced coronary hyperemia?
AB  - Introduction Growing evidence supports ischemia-guided management of chest pain,
      with invasive and non-invasive tests reliant upon achieving adenosine-induced
      coronary hyperemia (defined as increased blood flow to an organ's perfusion bed).
      In the non-invasive setting, surrogate markers of hyperemia, such as increases in
      heart rate, are often used, despite not being formally validated. We tested
      whether heart rate and other non-invasive indices are reliable markers of
      coronary hyperemia. Methods The first part involved Doppler flow-based validation
      of the best pressure-wire markers of hyperemia in 53 patients. Subsequently,
      using these validated pressure-derived parameters, 265 pressure-wire traces were
      analysed to determine whether heart rate and other non-invasive parameters
      correlated with hyperemia. Results In the flow derivation cohort, the best
      determinant of hyperemia came from having 2 out of 3 of: (1) Ventriculisation of
      the distal pressure waveform, (2) disappearance of distal dicrotic pressure
      notch, (3) separation of mean aortic and distal pressures. Within the 244
      patients demonstrating hyperemia, non-invasive markers of hyperemia, such as
      change in heart rate (p = 0.77), blood pressure (p = 0.60) and rate-pressure
      product (p = 0.86), were poor correlates of coronary hyperemia, with only 37.3%
      demonstrating a >= 10% increase in heart rate that is commonly used to adjudge
      adenosine-induced hyperemia in the non-invasive setting. Conclusions We
      demonstrate, by correlation with Doppler-flow data, a validated method of
      identifying coronary hyperemia within the catheter laboratory using the pressure
      wire. We subsequently show that non-invasive parameters, such as heart rate
      change, are poor predictors of coronary hyperemia during stress imaging protocols
      that rely upon achieving adenosine-induced hyperemia.

PMID- 29445974
TI  - Impact of acquisition and interpretation on total inter-observer variability in
      echocardiography: results from the quality assurance program of the STAAB cohort
      study.
AB  - Variability related to image acquisition and interpretation is an important issue
      of echocardiography in clinical trials. Nevertheless, there is no broadly
      accepted standard method for quality assessment of echocardiography in clinical
      research reports. We present analyses based on the echocardiography quality
      assurance program of the ongoing STAAB cohort study (characteristics and course
      of heart failure stages A-B and determinants of progression). In 43 healthy
      individuals (mean age 50 +/- 14 years; 18 females), duplicate echocardiography
      scans were acquired and mutually interpreted by one of three trained sonographers
      and an EACVI certified physician, respectively. Acquisition (AcV), interpretation
      (InV), and inter-observer variability (IOV; i.e., variability between the
      acquisition-interpretation sequences of two different observers), were determined
      for selected M-mode, B-mode, and Doppler parameters. We calculated Bland-Altman
      upper 95% limits of absolute differences, implying that 95% of measurement
      differences were smaller/equal to the given value: e.g. LV end-diastolic volume
      (mL): 25.0, 25.0, 27.9; septal e' velocity (cm/s): 3.03, 1.25, 3.58. Further, 90,
      85, and 80% upper limits of absolute differences were determined for the
      respective parameters. Both, acquisition and interpretation, independently and
      sizably contributed to IOV. As such, separate assessment of AcV and InV is likely
      to aid in echocardiography training and quality-assurance. Our results further
      suggest to routinely determine IOV in clinical trials as a comprehensive measure
      of imaging quality. The derived 95, 90, 85, and 80% upper limits of absolute
      differences are suggested as reproducibility targets of future studies, thus
      contributing to the international efforts of standardization in quality
      assurance.

PMID- 29445975
TI  - Factors of U.S. Hospitals Associated with Improved Profit Margins: An
      Observational Study.
AB  - BACKGROUND: Hospitals face financial pressure from decreased margins from
      Medicare and Medicaid and lower reimbursement from consolidating insurers.
      OBJECTIVES: The objectives of this study are to determine whether hospitals that
      became more profitable increased revenues or decreased costs more and to examine
      characteristics associated with improved financial performance over time. DESIGN:
      The design of this study is retrospective analyses of U.S. non-federal acute care
      hospitals between 2003 and 2013. SUBJECTS: There are 2824 hospitals as subjects
      of this study. MAIN MEASURES: The main measures of this study are the change in
      clinical operating margin, change in revenues per bed, and change in expenses per
      bed between 2003 and 2013. KEY RESULTS: Hospitals that became more profitable had
      a larger magnitude of increases in revenue per bed (about $113,000 per year [95%
      confidence interval: $93,132 to $133,401]) than of decreases in costs per bed
      (about - $10,000 per year [95% confidence interval: - $28,956 to $9617]), largely
      driven by higher non-Medicare reimbursement. Hospitals that improved their
      margins were larger or joined a hospital system. Not-for-profit status was
      associated with increases in operating margin, while rural status and having a
      larger share of Medicare patients were associated with decreases in operating
      margin. There was no association between improved hospital profitability and
      changes in diagnosis related group weight, in number of profitable services, or
      in payer mix. Hospitals that became more profitable were more likely to increase
      their admissions per bed per year. CONCLUSIONS: Differential price increases have
      led to improved margins for some hospitals over time. Where significant price
      increases are not possible, hospitals will have to become more efficient to
      maintain profitability.

PMID- 29445976
TI  - An equivalence study of interview platform: Does videoconference technology
      impact medical school acceptance rates of different groups?
AB  - Web-based interviewing may be an effective element of a medical school's larger
      approach to promotion of holistic review, as recommended by the Association of
      American Medical Colleges, by facilitating the feasibility of including rural and
      community physicians in the interview process. Only 10% of medical schools offer
      videoconference interviews to applicants and little is known about the impact of
      this interview modality on the admissions process. This study investigated the
      impact of overall acceptance rates using videoconference interviews and face-to
      face interviews in the medical school selection process using an equivalence
      trial design. The University of New Mexico School of Medicine integrated a
      videoconferencing interview option for community and rural physician interviewers
      in a pseudo-random fashion during the 2014-2016 admissions cycles. Logistic
      regression was conducted to examine whether videoconference interviews impacted
      acceptance rates or the characteristics of accepted students. Demographic,
      admissions and diversity factors were analyzed that included applicant age, MCAT
      score, cumulative GPA, gender, underrepresented in medicine, socioeconomic status
      and geographic residency. Data from 752 interviews were analyzed. Adjusted rates
      of acceptance for face-to-face (37.0%; 95% CI 28.2, 46.7%) and videoconference
      (36.1%; 95% CI 17.8, 59.5%) interviews were within an a priori +/- 5% margin of
      equivalence. Both interview conditions yielded highly diverse groups of admitted
      students. Having a higher medical college admission test score, grade point
      average, and self-identifying as disadvantaged increased odds of admission in
      both interview modalities. Integration of the videoconference interview did not
      impact the overall acceptance of a highly diverse and qualified group of
      applicants, and allowed rural and community physicians to participate in the
      medical school interview process as well as allowed campus faculty and medical
      student committee members to interview remotely.

PMID- 29445977
TI  - A Brief History of Biochemical Genetics' 50 Years and a Reflection About Past and
      Present Research Directions.

PMID- 29445978
TI  - Positive Developmental Changes after Transition to High School: Is Retrospective
      Growth Correlated with Measured Changes in Current Status of Personal Growth?
AB  - The transition to high school is generally considered as a stressful turning
      point in adolescent development, but some students experience personal growth
      (i.e., positive developmental changes) through that experience. It is important
      to examine the mechanism behind such positive changes to understand various
      developmental patterns of adolescents during the transition. However, the concept
      of growth in this research area remains unexplored. Some researchers have
      questioned whether retrospective, self-reported growth reflects actual positive
      changes in the perception of personal growth. We elaborated on the concept of
      growth after high school transition by examining whether retrospective appraisal
      of personal growth after transition to high school is correlated with measured
      change in growth. Two hundred and sixty-two Japanese adolescents (aged 14-16
      years, 50% girls) participated in surveys right before and right after
      transition. We assessed five domains of growth, including improved relating to
      others, identification of new possibilities, increased sense of personal
      strength, spiritual growth, and greater appreciation of life. The results showed
      that retrospective assessment of growth and measured change during transition
      were positively associated, provided the adolescents reported the transition as
      an important turning point in their lives. Adolescents who experienced salient
      positive changes across the transition were more likely to engage in intrusive
      and deliberate rumination and social support than adolescents who reported fewer
      changes. In summary, retrospective growth covaried with measured change only when
      adolescents perceived the transition as impactful in their lives.

PMID- 29445979
TI  - Hispanic Immigrant Father Involvement with Young Children in the United States: A
      Comparison with US-Born Hispanic and White non-Hispanic Fathers.
AB  - Objectives Fathering is known to foster child development and health, yet
      evidence on Hispanic immigrant fathers' involvement with their young children is
      sparse. This study assessed disparities in pregnancy intendedness and father
      involvement with children ages 0-4 among Hispanic immigrant co-resident fathers
      versus two reference groups: US-born Hispanic and US-born White fathers. We
      hypothesized that differentials in involvement were associated with socioeconomic
      and cultural factors. Methods Using 2011-2013 data from the National Survey of
      Family Growth (N = 598), we performed bivariate, logistic and linear regression
      analyses to assess disparities in pregnancy intendedness and five father
      involvement outcomes (physical care, warmth, outings, reading and discipline).
      The models controlled for socio-economic, structural, health and cultural
      covariates. Results Pregnancy intendedness did not differ significantly between
      Hispanic immigrant fathers and the two reference groups. Compared with US-born
      Hispanics, unadjusted models showed that immigrant fathers were less likely to
      engage in physical care, warmth and reading, (p <= 0.05) though the differences
      were attenuated when controlling for covariates. Hispanic immigrant fathers were
      less likely than US-born White fathers to engage in each of the father
      involvement outcomes (p <= 0.05), with the disparity in reading to their child
      persisting even after controlling for all covariates. Conclusions for Practice We
      found marked socio-economic and cultural differences between Hispanic immigrant
      and US-born Hispanic and White fathers which contribute to disparities in father
      involvement with their young children. Hispanic immigrant status is an important
      determinant of involved fathering and should be taken into account when planning
      public health policies and programs.

PMID- 29445980
TI  - Challenges and Facilitators to Promoting a Healthy Food Environment and
      Communicating Effectively with Parents to Improve Food Behaviors of School
      Children.
AB  - Background Childhood obesity is a major public health concern and families play
      an important role. Improving strategies to reach parents and directing tailored
      nutrition education to them is needed. Purpose To investigate the challenges and
      facilitators to promoting a healthy environment at home and to identify
      communication preferences to inform intervention strategies for effectively
      reaching low-income urban minority families. Procedure Semi-structured focus
      group interviews were conducted with four groups involving 16 low-income urban
      parents (94% female; 88% Hispanic/Latino, 12% African American) of elementary
      school children. Interviews were transcribed and analyzed applying Social
      Cognitive Theory and using in-vivo coding. Main Findings The most common barriers
      to parents providing healthy foods to their children were accommodating child
      preferences and familial opposition. Parents showed intentionality to engage in
      healthy behaviors, and often shared procedural knowledge for reaching health
      goals. The analyses of desired communication channels yielded major preferences:
      tailored information, information provided through multiple mediums, appropriate
      duration/frequency of messages, and presented from a voice of authority.
      Conclusion and Implication While parents expressed desires to be healthy, the
      home food environment presented substantial challenges. Multi-media supports such
      as workshops, flyers, and text messaging may be useful to facilitate the sharing
      of information to minimize the tensions between intentionality and reaching
      desired goals to be healthy. Some parents thought that information received
      through text messaging could be easily shared and would act as a voice of
      authority to support child behavior change.

PMID- 29445981
TI  - The Impact of Food Insecurity on the Home Emotional Environment Among Low-Income
      Mothers of Young Children.
AB  - Objectives Household stressors, such as food insecurity, contribute to the home
      emotional environment and negatively affect child development. Little research on
      this topic has been conducted among very young children. This study aimed to
      examine the relationship between food insecurity and the home emotional
      environment, as well the extent to which the relationship may be mediated by
      maternal symptoms of depression. Frequency of praise, affection, and discipline
      of young children by mothers were examined as markers of the home emotional
      environment. Methods Data were collected in a cross-sectional study of mothers of
      children under the age of five (N = 4231). Logistic regression was used to assess
      the relationship between level of food security and frequency of praise and
      discipline of children. Mediation analysis using the KHB method was conducted to
      test whether maternal mental health mediated the relationship between food
      insecurity and each outcome. Results Low and very low food security were
      significantly associated with higher odds of disciplining children with high
      frequency. Controlling for all covariates, frequency of praise was not
      significantly associated with level of household food insecurity. Differences in
      praise and discipline frequency were found by language of interview, maternal
      education, and employment. Conclusions for Practice Parent-child interactions,
      specifically related to discipline, are related to food insecurity. Further
      research should consider cultural patterns and mechanisms behind the relationship
      between food insecurity and the home environment. Household stressors begin
      affecting children at young ages, and early intervention is essential to prevent
      further negative sequelae as children grow older.

PMID- 29445982
TI  - Care Coordination: Empowering Families, a Promising Practice to Facilitate
      Medical Home Use Among Children and Youth with Special Health Care Needs.
AB  - Introduction This paper describes the care coordination training program and
      results of an evaluation from its pilot in seven states. Despite the importance
      of practice-based care coordination, only 42.3% of children with special health
      care needs (CYSHCN) met all needed components of care coordination as defined by
      the Maternal Child Health Bureau. Recognizing that children with medically
      complex conditions often have lower rates of achieving care coordination within a
      medical home, the Region 4 Midwest Genetics Collaborative worked with families to
      develop a training to empower families in care coordination. The Care
      Coordination: Empowering Families(CCEF) training provides families with the
      knowledge, tools, and resources to engage with health, education and family
      support systems. This article gives an overview of the training and comprehensive
      evaluation. Methods Participants were family caregivers of children with genetic
      conditions and other special health care needs recruited in one of seven pilot
      states. Evaluation data were collected from 190 participants prior to and
      immediately following the training. An additional follow-up assessment one full
      year post training was completed by 80 participants (a response rate of 42%).
      Results Families who attended the training report being the primary source of
      care coordination for their children and 83.7% see their role in their child's
      healthcare changing as a result of the training. The findings suggest that peer
      support and communication with providers increased as a result of the training
      over the course of the study. The data suggest that the training impacted how the
      family interacts with the child's doctor, including initiating conversations to
      prepare their child for transition to adult health care. Further, families report
      system-level improvements 1 year later compared to the pre-training assessment.
      Discussion CCEF training is a promising practice for facilitating medical home
      use among CYSHCN.

PMID- 29445983
TI  - Impact of the pulmonary vein orifice area assessed using intracardiac
      echocardiography on the outcome of radiofrequency catheter ablation for atrial
      fibrillation.
AB  - PURPOSE: The purposes of this study were to investigate pulmonary vein cross
      sectional orifice area (PV-CSOA) using intracardiac echocardiography (ICE) and to
      determine its association with atrial fibrillation (AF) recurrence after
      radiofrequency catheter ablation (RFCA). METHODS: We studied 77 patients
      undergoing initial RFCA for AF (55 paroxysmal and 22 persistent AF patients, mean
      age 61 +/- 12 years, 59 men). The PV-CSOA was measured in each patient and
      expressed as an index divided by the body surface area-left superior (LSPV-CSOA),
      left inferior (LIPV-CSOA), right superior (RSPV-CSOA), and right inferior (RIPV
      CSOA). RESULTS: After a mean follow-up of 21 +/- 14 months, 61 patients
      maintained sinus rhythm (non-recurrence group) and AF recurred in 16 patients
      (recurrence group). The LSPV-CSOA index was significantly greater in the
      recurrence group compared with the non-recurrence group (146 +/- 41 vs. 126 +/-
      30 mm2/m2, p = 0.04). A Cox regression multivariate analysis revealed that the
      LSPV-CSOA was the independent predictor of AF recurrence (HR 1.02, 95% CI 1.01
      1.04, p = 0.01). The LSPV-CSOA cutoff value of 154 mm2/m2 predicts AF recurrence
      with 50% positive predictive value and 89% negative predictive value.
      CONCLUSIONS: The present study suggests that ICE can be used as an alternative
      imaging tools for assessing the PV-CSOA during RFCA and that the LSPV-CSOA index
      was a useful independent predictor of AF recurrence after RFCA.

PMID- 29445984
TI  - Impact of antibiotic prophylaxis on catheter-associated urinary tract infections
      during atrial fibrillation ablation.
AB  - PURPOSE: Urinary catheter placement is common during atrial fibrillation (AF)
      ablation when performed under general anesthesia. Whether patients undergoing AF
      ablation would benefit from prophylactic antibiotics is unknown. METHODS:
      Patients undergoing AF ablation in a single center from December 2011 until June
      2016 were included. All patients received urinary catheters and general
      anesthesia. After June 2014, patients received antibiotic prophylaxis with a
      single dose of oral nitrofurantoin and a catheter insertion checklist performed
      prior to urinary catheter placement. The intervention group (group B) was
      compared to the pre-intervention group (group A) for development of the primary
      outcome. A multivariable logistic regression was performed to determine if any of
      the covariates were associated with catheter-associated urinary tract infection
      (CAUTI) development. RESULTS: There were 452 patients who underwent AF ablation
      during the analysis period (212 in group A and 240 in group B). The average
      patient age was 60 years (range 23-85) and 70% of the patients were male.
      Utilizing an intention to treat approach, there was a significantly lower
      incidence of CAUTI in the intervention group compared to controls (4.7 vs. 0.83%;
      OR 0.18, p = 0.029). There were no significant differences between the groups
      with respect to urinary tract infection risk factors or catheter duration.
      CONCLUSION: An intervention consisting of a single dose of nitrofurantoin in
      addition to performance of a catheter insertion checklist prior to urinary
      catheter insertion decreased CAUTI by 80% in patients undergoing AF ablation.
      Such interventions may be beneficial to reduce CAUTI in this group of patients.

PMID- 29445985
TI  - Acute pericarditis following second-generation cryoballoon ablation for atrial
      fibrillation.
AB  - PURPOSE: Acute pericarditis is a minor complication following atrial fibrillation
      (AF) ablation procedures. The aim of the study was to evaluate the incidence and
      clinical aspects of pericarditis following cryoballoon (CB) ablation of AF
      investigating a possible association with procedural characteristics and a
      possible relationship with post-ablation recurrences. METHODS: Four hundred fifty
      consecutive patients (male 73%, age 59.9 +/- 11.2 years) with drug-resistant
      paroxysmal AF who underwent CB ablation as index procedure were enrolled.
      Exclusion criteria were any contraindication for the procedure including the
      presence of intracavitary thrombus and uncontrolled heart failure and
      contraindications to general anesthesia. RESULTS: Acute pericarditis following CB
      ablation occurred in 18 patients (4%) of our study population. Pericardial
      effusion occurred in 14 patients (78%) and was mild/moderate. The total number of
      cryoapplications and the total freeze duration were significantly higher in
      patients with pericarditis compared with those without (respectively, p = 0.0006
      and p = 0.01). Specifically, the number of applications and freeze duration in
      right inferior pulmonary vein were found significantly higher in patients with
      pericarditis (p = 0.007). The recurrence rate did not significantly differ
      between the two study groups (respectively, 16.7 vs 18.1%; p = 0.9). CONCLUSIONS:
      The incidence of acute pericarditis following CB ablation in our study population
      accounted for 4% and was associated with both total freezing time and number of
      cryoapplications. The clinical course was favorable in all these patients and the
      occurrence of acute pericarditis did not affect the outcome during the follow-up
      period.

PMID- 29445986
TI  - Pain threshold and temporomandibular function in systemic sclerosis: comparison
      with psoriatic arthritis.
AB  - The aim of the study was to evaluate whether a reduced pain threshold is
      associated with increased temporomandibular dysfunction in systemic sclerosis
      (SSc) compared to psoriatic arthritis (PsA) and healthy controls. Ninety subjects
      participated in the study (30 SSc, 30 PsA, and 30 healthy controls). The Helkimo
      index was used to evaluate temporomandibular dysfunction. Digital palpation was
      performed at the temporomandibular joint (TMJ) surface and at the superficial
      masseter muscle (SMM) and pain intensity was recorded on a visual analog scale
      (VAS), while pain pressure threshold (PPT) was measured at the same sites through
      a pressure algometer. PPT scores were lower in SSc patients compared to PsA
      patients and controls. In addition, the average Helkimo index score, measuring
      the degree of TMJ dysfunction, was higher in SSc compared to PsA and controls. A
      significant inverse correlation was observed between every PPT score, and both
      Helkimo index and VAS palpation in SSc and PsA. Both the range of motion and all
      the other pain-related subdomains of the Helkimo index score (pain on movement,
      pain palpation TMJ and pain palpation muscle) were significantly worse in SSc
      compared to PsA, while no significant differences were observed in the TMJ
      function subdomain. In SSc patients, the skin score was directly associated with
      the range of motion subdomain of the Helkimo index. Our results confirm that TMJ
      function is impaired in SSc; further longitudinal studies are needed to assess
      the role of pain threshold in the assessment of limitations in TMJ function and
      to identify an objective marker of therapeutic response.

PMID- 29445987
TI  - The complete genome sequence of CrRV-Ch01, a new member of the family
      Rhabdoviridae in the parasitic copepod Caligus rogercresseyi present on farmed
      Atlantic salmon (Salmo salar) in Chile.
AB  - We have determined the complete genome sequence of a new rhabdovirus, tentatively
      named Caligus rogercresseyi rhabdovirus Ch01 (CrRV-Ch01), which was found in the
      parasite Caligus rogercresseyi, present on farmed Atlantic salmon (Salmo salar)
      in Chile. The genome encodes the five canonical rhabdovirus proteins in addition
      to an unknown protein, in the order N-P-M-U (unknown)-G-L. Phylogenetic analysis
      showed that the virus clusters with two rhabdoviruses (Lepeophtheirus salmonis
      rhabdovirus No9 and Lepeophtheirus salmonis rhabdovirus No127) obtained from
      another parasitic caligid, Lepeophtheirus salmonis, present on farmed Atlantic
      salmon on the west coast of Norway.

PMID- 29445988
TI  - Viral shedding and clinical status of feline-norovirus-infected cats after
      reinfection with the same strain.
AB  - Norovirus (NoV) infection is the most common cause of acute gastroenteritis in
      humans of all ages worldwide. When cats are experimentally infected with feline
      norovirus (FNoV), they develop symptoms of acute gastroenteritis. Therefore, FNoV
      infection may serve as an animal model for the disease caused by human norovirus
      infection. In this study, we examined whether FNoV of cats infected with
      genogroup GVI are protected from reinfection with the same strain. The blood anti
      FNoV IgG level was inversely correlated with the viral load in stool samples and
      the clinical score of FNoV-infected cats, but complete prevention of reinfection
      was not observed. These findings were similar to the results of a reinfection
      experiment with NoV in human volunteers.

PMID- 29445989
TI  - Relevance of sleep quality on caregiver burden in Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder which affects the
      quality of life of patient and their family. Sleep disorders appear in 80-90% of
      PD patients and have a great impact on the PD well-being. We examined the
      relationship of patients' sleep quality and depression on burden, mood, quality
      of life, and quality of sleep of their caregivers. A multicenter, regional
      (Veneto), observational, cross-sectional study that included 55 patient-caregiver
      pairs was conducted. Patients were assessed using Parkinson's Disease Sleep Scale
      (PDSS) and Epworth Sleepiness Scale (ESS) for sleep disorders, Beck Depression
      Inventory (BDI) as a measure of depression, and Parkinson's Disease Questionnaire
      (PDQ-39) as a measure of quality of life. Caregivers were evaluated by the
      Caregiver Burden Inventory (CBI) a measure of burden, BDI, SF-36 Health Survey as
      measures of HRQoL, and Medical Outcomes Study-Sleep Scale (MOS-SS) for quality of
      sleep. CBI, HRQoL, MOS-SS, and BDI scores displayed no association with patients'
      age, cognition (Mini Mental State Examination (MMSE) and Frontal Assessment
      Battery (FAB)), disease duration, and Hoehn and Yahr (H&Y), and UPDRS III scales
      whereas were significantly correlated with patients' quality of sleep,
      depression, and quality life. CBI and HRQoL were also associated respectively
      with patients' ESS and L-dopa daily dose. This study underscores the presence of
      a significant relationship between patient and caregiver quality of life.
      Interestingly, sleep quality and depression rather than motor disability best
      predicted caregivers' well-being.

PMID- 29445990
TI  - Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in
      inflammatory corneal neovascularization.
AB  - Inflammation in the normally immune-privileged cornea can initiate a pathologic
      angiogenic response causing vision-threatening corneal neovascularization.
      Inflammatory pathways, however, are numerous, complex and are activated in a time
      dependent manner. Effective resolution of inflammation and associated
      angiogenesis in the cornea requires knowledge of these pathways and their time
      dependence, which has, to date, remained largely unexplored. Here, using a model
      of endogenous resolution of inflammation-induced corneal angiogenesis, we
      investigate the time dependence of inflammatory genes in effecting capillary
      regression and the return of corneal transparency. Endogenous capillary
      regression was characterized by a progressive thinning and remodeling of
      angiogenic capillaries and inflammatory cell retreat in vivo in the rat cornea.
      By whole-genome longitudinal microarray analysis, early suppression of VEGF
      ligand-receptor signaling and inflammatory pathways preceded an unexpected later
      phase preferential activation of LXR/RXR, PPARalpha/RXRalpha and STAT3 canonical
      pathways, with a concurrent attenuation of LPS/IL-1 inhibition of RXR function
      and Wnt/beta-catenin signaling pathways. Potent downstream inflammatory cytokines
      such as Cxcl5, IL-1beta, IL-6 and Ccl2 were concomitantly downregulated during
      the remodeling phase. Upstream regulators of the inflammatory pathways included
      Socs3, Sparc and ApoE. A complex and coordinated time-dependent interplay between
      pro- and anti-inflammatory signaling pathways highlights a potential anti
      inflammatory role of LXR/RXR, PPARalpha/RXRalpha and STAT3 signaling pathways in
      resolving inflammatory corneal angiogenesis.

PMID- 29445991
TI  - Rainbow trout (Oncorhynchus mykiss) anesthesia with myrcene: efficacy and
      physiological responses in comparison with eugenol.
AB  - The aim of the present study was to investigate anesthetic efficacy of myrcene in
      rainbow trout (Oncorhynchus mykiss) along with the fish biochemical response to
      anesthesia in comparison with eugenol. In the first experiment, 240 fish were
      stocked in 12 tanks and acclimatized to experimental conditions for 2 weeks.
      Then, the fish of each tank were subjected to one concentration of either eugenol
      (12, 20, 30, 50, 80, and 130 MUL/L) or myrcene (100, 150, 200, 300, 400, and 500
      MUL/L) concentrations. Induction time of and recovery time from anesthesia were
      recorded for each fish separately. Using these results, desired concentrations to
      induce anesthesia within 60, 180, 300, and 600 s were determined, being 81, 30,
      19, and 10 MUL/L eugenol and 531, 251, 177, and 111 MUL/L myrcene. In the second
      experiment, 96 fish were stocked in 8 tanks. Six fish were netted from each tank
      and exposed to the calculated eugenol or myrcene concentrations. Blood samples
      were taken after the fish reached anesthesia. The results showed that there was
      no significant difference in serum lactate, alanine transaminase, and alkaline
      phosphatase. Increase in the induction time of anesthesia resulted in increased
      serum glucose with no significant difference between the anesthetics. Increase in
      induction time of anesthesia led to increase in serum lactate dehydrogenase
      activity in the eugenol-anesthetized fish and aspartate transaminase activity in
      myrcene-anesthetized fish. In conclusion, myrcene is capable to anesthetize
      rainbow trout, but at higher concentrations compared to eugenol. In addition,
      biochemical analysis showed that increase in induction time of anesthesia leads
      to hyperglycemia and increase in AST and LDH activities depending on anesthetic
      type.

PMID- 29445992
TI  - The functional genomics laboratory: functional validation of genetic variants.
AB  - Currently, one of the main challenges in human molecular genetics is the
      interpretation of rare genetic variants of unknown clinical significance. A
      conclusive diagnosis is of importance for the patient to obtain certainty about
      the cause of the disease, for the clinician to be able to provide optimal care to
      the patient and to predict the disease course, and for the clinical geneticist
      for genetic counseling of the patient and family members. Conclusive evidence for
      pathogenicity of genetic variants is therefore crucial. This review gives an
      introduction to the problem of the interpretation of genetic variants of unknown
      clinical significance in view of the recent advances in genetic screening, and
      gives an overview of the possibilities for functional tests that can be performed
      to answer questions about the function of genes and the functional consequences
      of genetic variants ("functional genomics") in the field of inborn errors of
      metabolism (IEM), including several examples of functional genomics studies of
      mitochondrial disorders and several other IEM.

PMID- 29445993
TI  - Unintended Consequences of Evidence-Based Treatment Policy Reform: Is
      Implementation the Goal or the Strategy for Higher Quality Care?
AB  - This study examined patterns of evidence-based treatment (EBT) delivery following
      a county-wide EBT reform initiative. Data were gathered from 60 youth and their
      21 providers, who were instructed to deliver therapy as they normally would under
      the EBT initiative. Results showed limited applicability of county-supported EBTs
      to this service sample, and that most youth did not receive traditional delivery
      of EBTs. Findings suggest that it may be unrealistic to expect providers to
      deliver EBTs with fidelity with all clients, and that EBT implementation may be
      best thought of as a strategy for improving mental health services rather than a
      goal.

PMID- 29445994
TI  - Estimation of Posturographic Trajectory Using k-Nearest Neighbors Classifier in
      Patients with Rheumatoid Arthritis and Osteoarthritis.
AB  - Rheumatoid arthritis (RA) and osteoarthritis (OA) are common rheumatic diseases
      and account for a significant percentage of disability. Posturography is a method
      that assesses postural stability and quantitatively evaluates postural sways. The
      objective of this study was to estimate posturographic trajectories applying
      pattern recognition algorithms. To this end, k-nearest neighbors (k-NN)
      classifier was used to differentiate between healthy subjects and patients with
      OA and RA. The following parameters of trajectories were computed: radius of
      sways, developed area, total length, and two directional components of sways:
      length of left-right and forward-backward motions. Posturographic tests were
      applied with eyes open and closed, and with biofeedback control. We found that in
      RA, the radius of sways, the trajectory area, and the biofeedback coordination
      were related to the patients' condition. The trajectory dynamics in OA patients
      were smaller compared to those in RA patients. The smallest misclassification
      errors were observed after feature selection in the biofeedback test compared
      with the eyes open and closed tests. We conclude that the estimation of
      posturographic trajectory with k-NN classifier could be helpful in monitoring the
      condition of RA patients.

PMID- 29445995
TI  - Long-Term Exposure to Ambient Air Pollution in Childhood-Adolescence and Lung
      Function in Adulthood.
AB  - The aim of the study was to evaluate the effect of air pollution in the dwelling
      place during childhood-adolescence on respiratory function in early adulthood.
      The study was conducted in 220 female and 160 male university undergraduates in
      the cities of Cracow and Wroclaw in Poland and consisted of spirometry to assess
      lung function. The subjects' exposure to pollution during childhood-adolescence
      was assessed from the data acquired by the Polish Chief Inspectorate for
      Environmental Protection. We found differences in all spirometry variables
      depending on benz[a]piren exposure, in FVC% and FEV1/%FVC depending on PM2.5
      content, and in FVC% depending on NO2 content. Statistically significant
      differences in spirometry variables were also found in relation to the degree of
      urbanization of the place of living during the early life period in question. The
      higher the urbanization, the higher is FEV1% and FCV%, and the lower FEV1/%FVC.
      Additionally, undergraduates of Cracow University had worse lung function
      compared to those of Wroclaw University. In conclusion, air pollution in the
      dwelling place during childhood-adolescence has an impact on lung function in
      early adulthood, independently of the current exposure to pollutants.

PMID- 29445996
TI  - Baker's Asthma: Is the Ratio of Rye Flour-Specific IgE to Total IgE More Suitable
      to Predict the Outcome of Challenge Test Than Specific IgE Alone.
AB  - Usually the diagnosis of baker's asthma is based on specific inhalation challenge
      with flours. To a certain extent the concentration of specific IgE to flour
      predicts the outcome of challenge test in bakers. The aim of this study was to
      evaluate whether the ratio of specific IgE (sIgE) to total IgE (tIgE) improves
      challenge test prediction in comparison to sIgE alone. Ninety-five bakers with
      work-related respiratory symptoms were challenged with rye flour. Total IgE,
      sIgE, and the sIgE/tIgE ratio were determined. Receiver operator characteristic
      (ROC) plots including the area under the curve (AUC) were calculated using the
      challenge test as gold-standard. Total IgE and sIgE concentrations, and their
      ratio were significantly higher in bakers with a positive challenge test than in
      those with a negative one (p < 0.0001, p < 0.0001, and p = 0.023, respectively).
      In ROC analysis, AUC was 0.83 for sIgE alone, 0.79 for tIgE, and 0.64 for the
      ratio. At optimal cut-offs, tIgE, sIgE, and the ratio reached a positive
      predicted value (PPV) of 95%, 84% and 77%, respectively. In conclusion,
      calculating the ratio of rye flour-sIgE to tIgE failed to improve the challenge
      test prediction in our study group.

PMID- 29445997
TI  - Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma: A Case Report
      Documenting the Potential for Very Late Tumor Recurrence.
AB  - Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma is a
      peculiar sinonasal tract tumor that demonstrates features of both a surface
      derived and salivary gland carcinoma. Implicit in its name, this tumor has a
      consistent association with high-risk HPV, particularly type 33. It was first
      described in 2013 under the designation of HPV-related carcinoma with adenoid
      cystic carcinoma-like features. However, since its initial description additional
      cases have emerged which demonstrate a wide morphologic spectrum and relatively
      indolent clinical behavior. Herein we report our experience with a case of HPV
      related multiphenotypic sinonasal carcinoma that was initially classified as
      adenoid cystic carcinoma in the 1980s. The patient recurred after a 30-year
      disease free interval. RNA in situ hybridization confirmed the presence of high
      risk HPV in both her recurrence and her initial tumor in the 1980s, which allowed
      for reclassification as HPV-related multiphenotypic sinonasal carcinoma. Our case
      adds to the literature of this relatively newly described entity and supports the
      indolent clinical behavior of this neoplasm but also demonstrates a potential for
      very late local recurrence.

PMID- 29445998
TI  - Regarding the Use of the Term "Cementum" in Pathologic Proliferations.

PMID- 29445999
TI  - The S190R mutation in the hemagglutinin protein of pandemic H1N1 2009 influenza
      virus increased its pathogenicity in mice.
AB  - Human influenza viruses preferentially bind to sialic acid-alpha2,6-galactose
      (SAalpha2,6Gal) receptors, which are predominant in human upper respiratory
      epithelia, whereas avian influenza viruses preferentially bind to SAalpha2,3Gal
      receptors. However, variants with amino acid substitutions around the receptor
      binding sites of the hemagglutinin (HA) protein can be selected after several
      passages of human influenza viruses from patients' respiratory samples in the
      allantoic cavities of embryonated chicken eggs. In this study, we detected an egg
      adapted HA S190R mutation in the pandemic H1N1 virus 2009 (pdmH1N1), and
      evaluated the effects of this mutation on receptor binding affinity and
      pathogenicity in mice. Our results revealed that residue 190 is located within
      the pocket structure of the receptor binding site. The single mutation to
      arginine at position 190 slightly increased the binding affinity of the virus to
      the avian receptor and decreased its binding to the long human alpha2,6-linked
      sialic acid receptor. Our study demonstrated that the S190R mutation resulted in
      earlier death and higher weight loss in mice compared with the wild-type virus.
      Higher viral titers at 1 dpi (days post infection) and diffuse damage at 4 dpi
      were observed in the lung tissues of mice infected with the mutant virus.

PMID- 29446000
TI  - See One, Do One, Teach One: A Practical Course on Methods in Mammary Gland
      Biology.

PMID- 29446001
TI  - Canakinumab treatment in renal transplant recipients with familial Mediterranean
      fever.
AB  - Colchicine is the first-line treatment for familial Mediterranean fever (FMF),
      preventing both inflammatory attacks as well as the development of amyloidosis in
      the majority of the patients. However approximately 5-10% of patients are
      colchicine resistant/intolerant. Side effects of colchicine are more prominent in
      renal transplant recipients due to interaction with immunosuppressive drugs. Anti
      interleukin (IL)-1 drugs (anakinra, canakinumab and rilonacept) have emerged as
      the most promising drugs in the treatment of colchicine-resistant and/or
      intolerant FMF. There are no existing reports in the literature on canakinumab
      use in renal transplant recipients with FMF. We report here the efficacy and
      safety of canakinumab in three renal transplant recipients who achieved a
      complete clinical response with elimination of attacks and normalization of serum
      C-reactive protein (CRP) levels without significant side effects. This highlights
      the advantage of use of this drug in this setting, which has a better
      tolerability compared to anakinra.

PMID- 29446002
TI  - Genomic characterization of the first oral avian papillomavirus in a colony of
      breeding canaries (Serinus canaria).
AB  - Papillomaviruses are non-enveloped, DNA viruses that infect skin and mucosa of a
      wide variety of vertebrates, causing neoplasias or simply persisting
      asymptomatically. Avian papillomaviruses, with six fully sequenced genomes, are
      the second most studied group after mammalian papillomaviruses. In this study, we
      describe the first oral avian papillomavirus, detected in the tongue of a dead
      Yorkshire canary (Serinus canaria) and in oral swabs of the same bird and other
      two live canaries from an aviary in Madrid, Spain. Its genome is 8,071 bp and
      presents the canonical papillomavirus architecture with six early (E6, E7, E1,
      E9, E2, E4) and two late open reading frames (L1 and L2) and a long control
      region between L1 and E6. This new avian papillomavirus L1 gene shares a 64%
      pairwise identity with FcPV1 L1, so it has been classified as a new species
      (ScPV1) within the Ethapapillomavirus genus. Although the canary died after
      showing breathing problems, there is no evidence that the papillomavirus caused
      those symptoms so it could be part of the oral microbiota of the birds. Hence,
      future investigations are needed to evaluate the clinical relevance of the virus.

PMID- 29446004
TI  - A comparative study of three small-field detectors for patient specific
      stereotactic arc dosimetry.
AB  - This paper examines the difference in patient specific dosimetry using three
      different detectors of varying active volume, density and composition, for
      quality assurance of stereotactic treatments. A PTW 60017 unshielded electron
      diode, an Exradin W1 scintillator, and a PTW 31014 PinPoint small volume
      ionisation chamber were setup in a Lucy 3D QA phantom, and were positioned at the
      isocentre of an Elekta Axesse, with beam modulator collimator, using Exactrac and
      a HexaPODTM couch. Dose measurements were acquired for 43 stereotactic arcs, and
      compared to BrainLAB iPlan version 3.0.0 treatment planning system (TPS)
      calculations using a pencil beam algorithm. It was found that for arcs with field
      sizes [Formula: see text] mm, the properties of a detector have minimal impact on
      the measured doses, with all three detectors agreeing with the TPS (to within
      5%). However, for field sizes [Formula: see text] mm, only the scintillator was
      found to yield results to within 5% of the TPS. The dose discrepancies were found
      to increase with decreasing field size. It is recommended that for field sizes
      [Formula: see text] mm, a water equivalent dosimeter like the Exradin W1
      scintillator be used in order to minimise detector composition perturbations in
      the measured doses.

PMID- 29446005
TI  - Assessing Oral Cancer Awareness Among Dental Students.
AB  - The aim of this study was to assess oral cancer awareness among undergraduate
      dental students in Marmara University Faculty of Dentistry. A validated
      questionnaire which tested oral cancer awareness was given to third- and fifth
      year students of the dental faculty of Marmara University. A total of 198
      students participated in this survey. Knowledge of oral cancer risk factors and
      diagnosis procedures, dentistry student's attitude towards oral cancers,
      management practice regarding oral cancer, and oral cancer information sources
      were assessed using 25 questions. The data were analyzed with IBM SPSS Statistics
      22.0 program. Among 198 participant dentistry students, there were 99 (50%) third
      grade and 99 (50%) fifth-grade students. The largest number of the third- and
      last-grade students identified tobacco (98%) and alcohol usage (87.4%), prior
      oral cancer lesions (94.9%), viral infections (91.9%), UV exposure (94.4%), betel
      quid chewing (84.8%), older age (62.1%), and low consumption of fruit and
      vegetables (85.4%). Both groups showed higher scores in indicating squamous cell
      carcinoma as the most common form of oral cancer (p < 0.05); yet, third-grade
      students performed significantly higher scores in indicating erythroplakia and
      leukoplakia for most likely to be precancerous (p = 0.001; p < 0.05). This study
      highlighted the importance of improved educational methods for dentistry on oral
      cancer detection and prevention.

PMID- 29446003
TI  - Development of a 'ready-to-use' tool that includes preventability, for the
      assessment of adverse drug events in oncology.
AB  - Background Adverse drug events (ADEs) occur frequently in oncology and justify
      continuous assessment and monitoring. There are several methods for detecting
      them, but the trigger tool method seems the most appropriate. Although a generic
      tool exists, its use for ADEs in oncology has not been convincing. The
      development of a focused version is therefore necessary. Objective To provide an
      oncology-focused trigger tool that evaluates the prevalence, harm, and
      preventability in a standardised method for pragmatic use in ADE surveillance.
      Setting Hospitals with cancer care in France. Method The tool has been
      constructed in two steps: (1) constitution of an oncology-centred list of ADEs;
      30 pharmacists/practitioners in cancer care from nine hospitals selected a list
      of ADEs using a method of agreement adapted from the RAND/UCLA Appropriateness
      Method; and (2) construction of three standardised dimensions for the
      characterisation of each ADE (including causality, severity, and preventability).
      Main outcome measure The main outcome measure was validation of the tool,
      including preventability criteria. Results The tool is composed of a final list
      of 15 ADEs. For each ADE, a 'reviewer form' has been designed and validated by
      the panel. It comprises (1) the trigger(s), (2) flowcharts to guide the reviewer,
      (3) criteria for grading harm, and (4) a standardised assessment of
      preventability with 6-14 closed sentences for each ADE in terms of therapeutic
      management and/or prevention of side-effects. Conclusion A complete 'ready-to
      use' tool for ADE monitoring in oncology has been developed that allows the
      assessment of three standardised dimensions.

PMID- 29446006
TI  - Exploring the chemical space of peptides for drug discovery: a focus on linear
      and cyclic penta-peptides.
AB  - Peptide and peptide-like structures are regaining attention in drug discovery.
      Previous studies suggest that bioactive peptides have diverse structures and may
      have physicochemical properties attractive to become hit and lead compounds.
      However, chemoinformatic studies that characterize such diversity are limited.
      Herein, we report the physicochemical property profile and chemical space of four
      synthetic linear and cyclic combinatorial peptide libraries. As a case study, the
      analysis was focused on penta-peptides. The chemical space of the peptide and N
      methylated peptides libraries was compared to compound data sets of
      pharmaceutical relevance. Results indicated that there is a major overlap in the
      chemical space of N-methylated cyclic peptides with inhibitors of protein-protein
      interactions and macrocyclic natural products available for screening. Also,
      there is an overlap between the chemical space of the synthetic peptides with
      peptides approved for clinical use (or in clinical trials), and to other approved
      drugs that are outside the traditional chemical space. Results further support
      that synthetic penta-peptides are suitable compounds to be used in drug discovery
      projects.

PMID- 29446007
TI  - Significance of early detection of acute kidney function worsening among
      outpatients having CKD using automatic calculation system for the rate of eGFR
      decline.
AB  - BACKGROUND: To retard progression of chronic kidney disease (CKD) and reduce end
      stage kidney disease, it is important to detect acute kidney function worsening
      on CKD (AW-CKD) immediately and bring back their kidney functions to baselines by
      appropriate treatment. However, in general outpatient practice, it is difficult
      to detect the change in the slope of estimated glomerular filtration rate (eGFR).
      METHODS: We made automatic calculation system for the rate of eGFR decline
      (DeltaeGFR), and retrospectively observed the situation of AW-CKD among
      outpatients, who had visited all clinical departments of Steel Memorial Hirohata
      Hospital between May and August 2016, using the system. The patients with
      DeltaeGFR over 20 mL/min/1.73 m2/year were classified into "Detected cases", who
      were immediately detected AW-CKD by the attending physicians, and "Not detected
      cases". For each stratum of DeltaeGFR, subsequent eGFR recovery rates between two
      groups were compared. RESULTS: Among 6719 outpatients, 865 had CKD stages G3-5
      and of which 196 had DeltaeGFR over 20 mL/min/1.73 m2/year. We revealed that, in
      cases of DeltaeGFR over 30 mL/min/1.73 m2/year, eGFR recovery rates in "Detected
      cases" were significantly higher than those in "Not detected cases" (103.2 vs
      43.9%, p < 0.001). There were no differences in the clinical backgrounds except
      kidney function between two groups. CONCLUSION: In general outpatient practice, a
      substantial number of AW-CKD was latent. It is expected to improve kidney
      prognoses of outpatients having CKD through immediately detecting the patients,
      whose DeltaeGFR over 30 mL/min/1.73 m2/year using the system and alerting the
      attending physicians on the electronic medical record.

PMID- 29446008
TI  - Enhanced resistance to citrus canker in transgenic mandarin expressing Xa21 from
      rice.
AB  - Genetic engineering approaches offer an alternative method to the conventional
      breeding of Citrus sp. 'W. Murcott' mandarin (a hybrid of 'Murcott' and an
      unknown pollen parent) is one of the most commercially important cultivars grown
      in many regions around the world. Transformation of 'W. Murcott' mandarin was
      achieved by direct DNA uptake using a protoplast transformation system. DNA
      construct (pAO3), encoding Green Fluorescent Protein (GFP) and the cDNA of Xa21,
      a Xanthomonas resistance gene from rice, was used to transform protoplasts of 'W.
      Murcott' mandarin. Following citrus protoplast culture and regeneration,
      transformed micro calli were microscopically designated via GFP expression,
      physically isolated from non-transformed tissue, and cultured on somatic
      embryogenesis induction medium. More than 150 transgenic embryos were recovered
      and from them, ten transgenic lines were regenerated and cultured on rooting
      medium for shoot elongation. Transgenic shoots were micrografted and established
      in the greenhouse with 3-5 replicates per line. The insertion of Xa21 and GFP was
      confirmed by PCR and southern blot analysis. GFP expression was verified by
      fluorescence microscopy and western blot analysis revealed expression of Xa21
      although it was variable among transgenic lines, as shown by RT-qPCR. Transgenic
      plants challenged with the citrus canker pathogen by syringe inoculation showed a
      reduction in lesion number and bacterial populations within lesions compared to
      non-transgenic control plants. Transgenic 'W. Murcott' mandarin lines with
      improved canker resistance via protoplast transformation from embryogenic callus
      with the Xa21 gene from rice are being evaluated under field conditions to
      validate the level of resistance.

PMID- 29446009
TI  - The ethics of separating conjoined twins: two arguments against.
AB  - I argue that the separation of conjoined twins in infancy or early childhood is
      unethical (rare exceptions aside). Cases may be divided into three types: both
      twins suffer from lethal abnormalities, only one twin has a lethal abnormality,
      or neither twin does. In the first kind of case, there is no reason to separate,
      since both twins will die regardless of treatment. In the third kind of case, I
      argue that separation at an early age is unethical because the twins are likely
      to achieve an irreplaceably good quality of life-the goods of conjoinment-that
      separation takes away. Evaluation of this possibility requires maturation past
      early childhood. Regarding the second type, I point out that with conceivable but
      unrecorded exceptions, these cases will consistently involve sacrifice
      separation. I present an argument that sacrifice separation is unethical, but in
      some cases a moral dilemma may exist in which separation and refraining from
      separation are both unethical. Perhaps in such cases a decision can be made on
      non-moral grounds; however, the possibility of such a decision serves not to
      mitigate but to underscore the fact that the separation is unethical. My
      conclusion, which applies to all three types of cases, is that it is unethical to
      separate conjoined twins before their developing personalities give some reliable
      indication as to whether they desire separation and whether they will achieve
      those goods of conjoinment.

PMID- 29446010
TI  - Phosphaturic mesenchymal tumors: what an endocrinologist should know.
AB  - Tumor-induced osteomalacia (TIO), also known as "oncogenic osteomalacia", is a
      rare cause of osteomalacia. TIO often has an insidious onset characterized
      clinically by progressive muscle weakness and bone pain with fractures. The
      hallmark biochemical finding is a persistent low serum phosphorus concentration
      due to renal phosphate wasting. The vast majority of cases of TIO result from
      production of the phosphaturic hormone fibroblast growth factor 23 (FGF23) by a
      histologically distinctive mesenchymal tumor, termed "phosphaturic mesenchymal
      tumor" (PMT). Circulating FGF23 induces internalization of renal sodium/phosphate
      co-transporters resulting in reduced proximal tubular phosphate reabsorption.
      FGF23 also inhibits production of 1alpha,25-dihydroxyvitamin D which is
      inappropriately low or normal in the context of hypophosphatemia. Diagnosis is
      often delayed owing to the rarity of the condition and an underappreciation for
      the role of phosphorus as a cause for the constellation of symptoms. Primary
      treatment for TIO is identification of the offending tumor and surgical removal.
      However, these tumors are notoriously difficult to find, precluding the
      opportunity for a curative surgery in many. In such cases, phosphate and
      calcitriol therapy is used to improve symptoms and heal the osteomalacia.
      Recently, molecular genetic studies have shown recurrent genetic events in PMT,
      including the novel fusions FN1-FGFR1 and less commonly FN1-FGF1. These fusion
      events are hypothesized to result in autocrine/paracrine signaling loops within
      the tumor, spurring tumorigenesis. This review will cover the clinical features,
      imaging characteristics, pathologic features, molecular genetic aspects, and
      therapy of PMT, with a brief discussion of other neoplasms that may cause TIO.

PMID- 29446011
TI  - Continuously sustained elimination of iodine deficiency: a quarter of a century
      success in the Islamic Republic of Iran.
AB  - BACKGROUND: Iodine deficiency and related disorders were very common in Iran
      prior to 1996, when universal salt iodization (USI) was implemented and in 2000
      Iran was declared iodine deficiency disorders (IDD) free. The aim of this study
      was to evaluate the adequacy of iodine intake by Iranian households in all 30
      provinces of Iran, a quarter of a century after the intervention. METHODS: A
      total of 18,000 school-aged children (8-10 years with mean 8.7 +/- 1 year) were
      included in this study. Urine samples were collected from all children for
      measurement of urinary iodine excretion and 1800, 210 and 3000 salt samples were
      randomly collected from the family kitchen, production site of 73 salt factories
      and distribution circles of 30 provinces, respectively. RESULTS: The median
      urinary iodine concentration (UIC) of participants was 161 MUg/L. The proportion
      of children with UIC of, 20-49, 50-99 and >= 100 MUg/L were 10.3, 15.9 and 73.7%,
      respectively. The mean (+/- SD) and median salt iodine values were 28.2 (+/-
      12.6) and 31.7 ppm, at the production site, and 31.5 (+/- 13.6) and 29.6 ppm at
      the distribution circles, respectively. About 80% of factory salts had more than
      20 ppm iodine. 98% of households consumed iodized salt, 80% had appropriate salt
      storage, and 83% of the household salts contained >= 20 ppm. CONCLUSIONS: Based
      on the results of this study, Iranian populations are consuming adequate iodine.
      The well-maintained and monitored USI program has improved the dietary iodine
      intakes of the population, and the country has achieved all criteria of a well
      controlled IDD program.

PMID- 29446013
TI  - Chronic graft-specific cell-mediated immune response toward candidate xenogeneic
      biomaterial.
AB  - Despite rabbits becoming an increasingly popular animal model, a flow cytometry
      panel that combines T cell markers (CD3, CD4, CD8, CD25, FOXP3) with a method for
      monitoring proliferation is lacking in this species. It has been shown that the
      rabbit model can be used to identify xenoantigens within bovine pericardium (BP),
      a common biological heart valve replacement material; however, these methods rely
      on monitoring the humoral immune response. The development of a rabbit T cell
      proliferation assay has utility in monitoring graft-specific cell-mediated immune
      responses toward bovine pericardium. Isolation and culture conditions were
      optimized to avoid cell death, red blood cell contamination, and non-specific
      proliferation. Effect of cell culture and stimulation on distribution and
      intensity of T cell markers was analyzed and compared between cells isolated from
      naive and BP-immunized rabbits. Submaximal levels (0.25 MUg/mL) of concavalin A
      were used to stimulate proliferation toward BP extract, with resultant
      proliferation compared between naive and BP-immunized rabbits. Density
      stratification followed by ammonium potassium chloride (ACK) lysis yielded the
      greatest number of viable peripheral blood mononuclear cells with the least
      amount of erythrocyte contamination. Flat-bottomed plates were necessary to
      reduce non-specific proliferation in culture. T cells responded appropriately to
      maximal mitogenic stimulation (5 MUg/mL concavalin A). Interestingly,
      immunization increased the intensity of FOXP3 in T regulatory cells compared to
      cells from naive animals. With addition of submaximal levels of concavalin A, T
      cells from immunized rabbits proliferated in response to BP protein extract,
      while cells from naive rabbits did not. In immunized rabbits, not only did more
      CD4+ T cells proliferate in response to BP re-stimulation, but the intensity of
      CD25 was increased indicating cell activation. This research provides a
      functional cell-mediated screening assay for assessment of BP-based biomaterials
      in rabbits, overcoming the limitations of previous humoral immune system-based
      assessments of biomaterial antigenicity in this important experimental animal
      species.

PMID- 29446014
TI  - Breast Cancer Survivors Report Similar Concerns Related to Return to Work in
      Developed and Developing Nations.
AB  - Aim To determine whether breast cancer survivors (BCS) at work following the
      diagnosis and/or treatment of breast cancer, in a rapidly developing country such
      as China experience similar to return to work challenges as reported in nations
      with established return to work (RTW) policy and procedures for employees with
      cancer. Methods Semi-structured interviews were conducted with 16 BCS who
      returned to work following diagnosis and/or primary cancer treatment. An
      Interpretative Phenomenological Analysis was used to investigate responses.
      Results Three recurring themes emerged: (1) challenges at work related to
      residual effects of diagnosis and/or primary treatment; (2) positive and negative
      responses from employers and/or supervisors; and (3) positive and negative
      responses from co-workers/colleagues. Although several participants experienced a
      high level of workplace support, there was a subgroup that did report challenges
      related to symptom burden, cognitive limitations, and both positive and negative
      responses by employers and co-workers were reported. Conclusions Findings
      indicate similar challenges in BCS who RTW during and/or following cancer
      treatment in both rapidly developing and developed nations. Results suggest that
      regardless of the existence of workplace policies and practices related to RTW
      for workers with a history of cancer, a subgroup of BCS experience similar
      challenges when returning to work. These findings highlight the international
      nature of RTW challenges and suggest the need for more global efforts to develop
      and evaluate workplace interventions to assist with these similarities.

PMID- 29446012
TI  - A meta-analysis of the effects of antidepressants on cognitive functioning in
      depressed and non-depressed samples.
AB  - A thorough understanding of the cognitive effects of antidepressant medications
      is essential given their frequency of use. This meta-analysis was conducted to
      investigate whether antidepressants differentially affect the various domains of
      cognitive functioning for depressed and non-depressed participants. An electronic
      search of PsycInfo, Medline and Google Scholar was conducted for all journal
      articles published between January 1998 and January 2017. Thirty-three studies
      were included enabling calculation of Hedges' g using a random effects model for
      the cognitive domains of divided attention, executive function, expressive
      language, immediate memory, perceptual motor skills, processing speed, recent
      memory, sustained attention, visuospatial-constructional skills and working
      memory. Results revealed that overall, antidepressants have a modest, positive
      effect on divided attention, executive function, immediate memory, processing
      speed, recent memory and sustained attention for depressed participants.
      Selective serotonin reuptake inhibitors (SSRI's) were found to have the greatest
      positive effect on cognition for depressed participants, as compared to the other
      classes of antidepressants analysed. Antidepressants did not significantly affect
      cognitive function in non-depressed participants.

PMID- 29446016
TI  - Removal of organochlorine pesticides from lindane production wastes by
      electrochemical oxidation.
AB  - This study is focused on the effective removal of recalcitrant pollutants
      hexaclorocyclohexanes (HCHs, isomers alpha, beta, gamma, and delta) and
      chlorobenzenes (CBs) present in a real groundwater coming from a landfill of an
      old lindane factory. Groundwater is characterized by a total organic carbon (TOC)
      content of 9 mg L-1, pH0 = 7, conductivity = 3.7 mS cm-1, high salt concentration
      (SO42-, HCO3-, Cl-), and ferrous iron in solution. The experiments were performed
      using a BDD anode and a carbon felt (CF) cathode at the natural groundwater pH
      and without addition of supporting electrolyte. The complete depletion of the
      four HCH isomers and a mineralization degree of 90% were reached at 4-h
      electrolysis with a current intensity of 400 mA, the residual TOC (0.8 mg L-1)
      corresponding mainly to formic acid. A parallel series reaction pathway was
      proposed: HCHs and CBs are transformed into chlorinated and hydroxylated
      intermediates that are rapidly oxidized to non-toxic carboxylic acids and/or
      mineralized, leading to a rapid decrease in solution pH.

PMID- 29446017
TI  - Transformation of heavy metal fractionation under changing environments: a case
      study of a drainage system in an e-waste dismantling community.
AB  - The change in environmental conditions during the transportation of contaminated
      soil and sediment was expected to affect the transformation of heavy metal
      fractionation. This study disclosed the serious contamination of copper (Cu),
      lead (Pb), and zinc (Zn) in the sewer sediment of an e-waste dismantling
      community in Thailand which may be caused by flushed contaminated soil and e
      waste fragments. Two environmental conditions were simulated to observe the
      transformation of heavy metal fractionation. The anoxic sewer condition was
      induced using high substrate and sulfate in a closed container. The aeration of
      anoxic contaminated sediment was applied to simulate the transformation to an
      oxidative environment. The BCR sequential extraction was applied for heavy metal
      fractionation in this study. The study results exhibited that when heavy metal
      contaminated soil was transferred into this induced anoxic condition,
      fractionation was redistributed based on the chemical change of system that tends
      to be associated into F3 (oxidizable fraction) > F2 (reducible fraction) > F1
      (acid soluble/exchangeable fraction). Cu exhibited the outstanding capability
      association to F3. The iron sulfide was not observed as usual due to its lower
      capability than Cu, Pb, and Zn. When contaminated sediment was transported to a
      more oxidative environment, the heavy metals fractionation would be redistributed
      again among those new environment media. It is noteworthy that F3 of Cu was
      stable even in oxic conditions. F2 of Fe was not developed by this oxic
      condition, possibly because its dehydration process was limited. The
      redistribution under an oxic environment became F1 > F2 > F3 indicating their
      more available form. This transformation was imperative and should be taken into
      account in heavy metal contaminated site management and control.

PMID- 29446015
TI  - Synthetic polymeric biomaterials for wound healing: a review.
AB  - Wounds are of a variety of types and each category has its own distinctive
      healing requirements. This realization has spurred the development of a myriad of
      wound dressings, each with specific characteristics. It is unrealistic to expect
      a singular dressing to embrace all characteristics that would fulfill generic
      needs for wound healing. However, each dressing may approach the ideal
      requirements by deviating from the 'one size fits all approach', if it conforms
      strictly to the specifications of the wound and the patient. Indeed, a functional
      wound dressing should achieve healing of the wound with minimal time and cost
      expenditures. This article offers an insight into several different types of
      polymeric materials clinically used in wound dressings and the events taking
      place at cellular level, which aid the process of healing, while the biomaterial
      dressing interacts with the body tissue. Hence, the significance of using
      synthetic polymer films, foam dressings, hydrocolloids, alginate dressings, and
      hydrogels has been reviewed, and the properties of these materials that conform
      to wound-healing requirements have been explored. A special section on bioactive
      dressings and bioengineered skin substitutes that play an active part in healing
      process has been re-examined in this work.

PMID- 29446018
TI  - Green synthesis of silver nanoparticles using Piper nigrum: tissue-specific
      bioaccumulation, histopathology, and oxidative stress responses in Indian major
      carp Labeo rohita.
AB  - The aim of the present investigation is to assess the sublethal toxicity of
      biologically synthesized silver nanoparticles (Ag NPs) in Indian major carp Labeo
      rohita. Ag NPs used in the study were synthesized by using AgNO3 with aqueous
      leaf extract of Piper nigrum. Median lethal concentration (LC50) of synthesized
      Ag NPs was determined for 96 h (25 MUg/L); 2.5 MUg/L (1/10th LC50) and 5 MUg/L
      (1/5th LC50) were taken as sublethal concentrations to evaluate the toxicity for
      35 days. The results of the TEM, SEM, and EDX analyses revealed that Ag NPs were
      considerably accumulated in the gill, liver, and kidney of fish at both
      concentrations (2.5 and 5 MUg/L). Consequently, the activity of the antioxidant
      enzymes, SOD and CAT, was significantly (P < 0.05) decreased in the gill, liver,
      and kidney when compared to the control group during the study period. However,
      lipid peroxidase (LPO) activity in the gill, liver, and kidney was significantly
      (P < 0.05) increased, and the result concluded a possible sign of free radical
      induced oxidative stress in Ag NP-exposed fish than the sham-exposed individuals.
      The histopathological study also confirmed the alterations such as degeneration
      of lamella, lifting of lamellar epithelium, hepatic necrosis, pyknotic nuclei,
      increased intracellular space, and shrinkage of glomerulus elicited by Ag NPs in
      the gill, liver, and kidney of Labeo rohita with two different concentrations.
      The findings of the present study revealed that green synthesis of Ag NPs from
      Piper nigrum at sublethal concentrations leads to accumulation of Ag, oxidative
      stress, and histopathological alterations in the target organs of the fish, Labeo
      rohita.

PMID- 29446019
TI  - Evaluation of vulnerable PM2.5-exposure individuals: a repeated-measure study in
      an elderly population.
AB  - Numerous studies have shown that elderly people are susceptible to high-level
      particles with aerodynamic diameter <= 2.5 MUm (PM2.5) exposure. However, not all
      elderly people exposed to PM2.5 suffer from diseases. In this study, we aim to
      establish a method to predict the vulnerable PM2.5-exposure individuals among
      elderly population. Fourteen elderly people were recruited from May 8 to July 4,
      2016, in Nanjing, China. Ten physiological indicators were repeatedly measured
      for 15 times. Liner mixed-effects model, principal component analysis (PCA), and
      PM2.5 lag score were used to estimate the effects of PM2.5 on blood pressure,
      pulse, and lung function. As a result, each quartile increase of ambient PM2.5
      was significantly associated with increased pulse (P < 0.05 for lag0, 1, 4, 0-1,
      0-2, 0-3, and 0-5 days), decreased blood pressure (P < 0.05 for lag4 and 0-3
      days), and decreased lung function (P < 0.05 for lag0, 1, 0-1, and 0-2 days)
      among the 14 elderly people. In terms of pulse or lung function, three elderly
      people were considered as vulnerable PM2.5-exposure individuals. No vulnerable
      individual was found for blood pressure. Blood pressure, pulse, and lung function
      could be affected by high-level PM2.5 exposure in elderly people. This method for
      screening three elderly people may provide a new insight on identifying the
      vulnerable PM2.5-exposure individuals.

PMID- 29446020
TI  - Achieving an extraordinary high organic and hydraulic loadings with good
      performance via an alternative operation strategy in a multi-stage constructed
      wetland system.
AB  - In this study, a high organic loading rate of 58-146 g BOD5/m2 day with a
      hydraulic loading rate (HLR) of 1.63 m3/m2 day and retention time (RT) of 16 h
      was achieved to maximize the treatment capacity of a four-stage alum sludge-based
      constructed wetland (CW) system. An alternative operation strategy, i.e., the
      first stage anaerobic up-flow and the remaining stage tidal flow with effluent
      recirculation, was investigated to achieve the goal with good treatment
      performance of 82% COD, 91% BOD5, 92% SS, 94% NH4-N, and 82% TN removal. Two
      kinetic models, i.e., first-order model and Monod plus continuous stirred-tank
      reactor (CSTR) flow model, were employed for predicting the removal dynamics. The
      results showed that the tidal flow strategy enhances oxygen transport and
      diffusion, thus improving reduction of organics and NH4-N. Effluent recirculation
      could further increase elimination of organics by extending the interaction time
      and also benefit the denitrification process. In addition, denitrification could
      be further enhanced by anaerobic up-flow in the first stage.

PMID- 29446021
TI  - Characteristics and mechanisms of cadmium adsorption from aqueous solution using
      lotus seedpod-derived biochar at two pyrolytic temperatures.
AB  - Herein, biochar derived from lotus seedpods, as an effective adsorbent, was
      prepared by pyrolysis method at 300 and 600  degrees C. The physicochemical
      characteristics and cadmium adsorption properties were studied systematically by
      batch adsorption experiments, FTIR, SEM-EDX, XRD, and XPS. Cd adsorption onto
      lotus seedpod-derived biochar was better fitted using Freundlich isotherm and
      pseudo-second-order model. Adsorption capacity of biochar produced at 300 and 600
      degrees C was 31.69 and 51.18 mg g-1, respectively. The Cd adsorption capacity
      of biochar was related to its characteristics determined by pyrolysis
      temperature, including carbonization, surface area, surface morphology, and
      surface functional groups. Cd adsorption on lotus seedpod-derived biochar
      revealed that adsorption was controlled by multiple mechanisms including surface
      complexation, ion exchange, surface precipitation, and Cd-pi interaction. This
      study showed that lotus seedpod-derived biochar is an effective and
      environmentally friendly adsorbent for water treatment.

PMID- 29446022
TI  - Removal of MCs by Bi2O2CO3: adsorption and the potential of photocatalytic
      degradation.
AB  - Microcystins (MCs) is a kind of hepatotoxin, which is the secondary metabolite of
      cyanobacteria. Bi2O2CO3 (BOC) is a kind of cheap and nontoxic semiconductor
      material. BOC was synthetized by solvothermal method and then microcystin-LR (MC
      LR) and microcystin-RR (MC-RR) were removed by BOC, through adsorption and
      photocatalytic degradation. When the dosage of BOC is 6 g/L, the MC-LR and MC-RR
      in the natural water sample can be completely adsorbed in 30 min and then after
      12 h irradiation, MC-LR and MC-RR were photocatalytically degraded by BOC.

PMID- 29446023
TI  - Comparing the adsorption mechanism of Cd by rice straw pristine and KOH-modified
      biochar.
AB  - Biochar was considered as an effective and novel sorbent for cadmium (Cd)
      adsorption from aqueous solution. In this study, the adsorption isotherm
      investigations were conducted to examine the effect of biochar produced via
      pyrolysis from rice straw on removing aqueous Cd before and after modification by
      2 M KOH solution. Langmuir and Freundlich adsorption isotherms can preferably
      describe the adsorption process. Results showed that the highest adsorption
      capacity of pristine rice straw biochar was 12.17 mg g-1. The chemically modified
      rice straw biochar showed greater Cd adsorption capacity of 41.9 mg g-1, which
      was more than three times that of pristine biochar. Increase of surface area and
      changes of porous structure, especially the functional groups on the surface of
      modified biochar, were the major contributors to its more efficient adsorption of
      Cd. The possible mechanisms for Cd adsorption by biochar mainly involve (1)
      surface precipitation by forming insoluble Cd compounds in alkaline condition and
      (2) ion exchange for Cd with exchangeable cations in the biochar, such as calcium
      ions, which were confirmed by FTIR, XRD, SEM, and zeta potential determination.

PMID- 29446024
TI  - Pharmaceuticals and detergents in hospital and urban wastewater: comparative
      monitoring, treatment, and assessment of impacts.

PMID- 29446025
TI  - Healing potential of Adiantum capillus-veneris L. plant extract on bisphenol A
      induced hepatic toxicity in male albino rats.
AB  - Bisphenol A (BPA) is a widely used environmental pollutant in the production of
      plastics but causes hepatotoxicity in mammals. In the present study, we studied
      the BPA-induced oxidative stress in rats and ameliorative potential of Adiantum
      capillus-veneris L. plant. It was concluded that the BPA can reduce the body and
      liver weight, increase in biochemical levels of alanine aminotransferase (ALT)
      and aspartate aminotransferase (AST), total bilirubin, and disturb the normal
      hepatic physiology, histology, and metabolism. Additionally, liver histology
      shows hepatic necrosis, congestion, and vacuolization in exposed individuals. In
      contrast, simultaneous exposure of A. capillus-veneris and BPA showed declining
      trend in serum biomarker levels and normal histopathological structures. We
      conclude that the A. capillus-veneris plant is antioxidant in nature and can
      reduce the BPA-induced toxicity. These findings are very helpful to understand
      the BPA-induced hepatic toxicity and ameliorative potential of A. capillus
      veneris plant and are of great importance in risk assessment of xenobiotics.

PMID- 29446026
TI  - Potentially useful elements (Al, Fe, Ga, Ge, U) in coal gangue: a case study in
      Weibei coal mining area, Shaanxi Province, northwestern China.
AB  - Coal gangue has become one of the largest industrial solid waste in China, but it
      is also a kind of reserve resources. Representative coal gangue samples from
      different coal mines (mainly in Permo-Carboniferous and Jurassic) in Weibei area
      in Shaanxi Province are collected, and potentially useful elements (Al, Fe, Ga,
      Ge, U) in coal gangue are analyzed. The results show that the reserves of Al and
      Fe in Chinese coal gangue are 262 million tons and 196 million tons,
      respectively, based on the geometric mean values of Al2O3 (15.18%, weight
      percent) and Fe2O3 (6.24%, weight percent). Meanwhile, the crude reserves
      estimation of Ga, Ge, and U are 55,282, 6867, and 32,981 tons, respectively,
      based on the weighted mean contents of Ga, Ge, and U in coal gangue at 17.55,
      2.18, and 10.47 mg/kg, respectively. Furthermore, Ga and Al contents in quite a
      large number of coal gangue mines exceed the cutoff value, which has a prospect
      of development and utilization from coal gangue. The policy implications from
      this study may include that (1) recycling of useful elements in Chinese coal
      gangue should be treated as an integral part of sustainable development with
      professional legislations and (2) establishing a basic database of coal gangue
      and authoritative system with relevant departments for solid waste management may
      effectively improve comprehensive utilization of coal gangue in the future.

PMID- 29446028
TI  - Ridge sowing of sunflower (Helianthus annuus L.) in a minimum till system
      improves the productivity, oil quality, and profitability on a sandy loam soil
      under an arid climate.
AB  - Sunflower (Helianthus annuus L.) is a major oilseed crop grown for its edible oil
      across the globe including Pakistan. In Pakistan, the production of edible oil is
      less than the required quantity; the situation is being worsened with the
      increasing population. Thus, there is dire need to grow those sunflower genotypes
      which perform better under a given set of agronomic practices. In this 2-year
      study, we compared four sunflower genotypes, viz., Armoni, Kundi, Sinji, and S
      278 for their yield potential, oil contents, fatty acid composition, and
      profitability under three sowing methods, viz., bed sowing, line sowing, and
      ridge sowing and two tillage system, viz., plow till and minimum till. Among the
      sunflower genotypes, the genotype Armoni produced the highest plant height,
      number of leaves, head diameter, 1000-achene weight, and achene yield; the oil
      contents and oleic acid were the highest in genotype Sinji. Among the sowing
      methods, the highest number of leaves per plant, head diameter, number of achenes
      per head, achene yield, and oil contents were recorded in ridge sowing. Among the
      tillage systems, the highest head diameter 16. 2 cm, 1000-achene weight (57.2 g),
      achene yield (1.8 t ha-1), oil contents (35.2%), and oleic acid (15.2%) were
      recorded in minimum till sunflower. The highest net benefits and benefit to cost
      ratio were recorded in minimum till ridge sown Armoni genotype. In conclusion,
      the genotype Armoni should be grown on ridges to achieve the highest achene
      yield, oil contents, and net profitability.

PMID- 29446027
TI  - Review of the methods for determination of reactive oxygen species and suggestion
      for their application in advanced oxidation induced by dielectric barrier
      discharges.
AB  - Advanced oxidation processes (AOPs) particularly non-thermal plasmas based on
      electrical discharges have been widely investigated for water and wastewater
      treatment. Dielectric barrier discharges (DBDs) generate large amounts of
      selective and non-selective reactive oxygen species (ROS) such as ozone, hydrogen
      peroxide, atomic oxygen, superoxide molecular anions and hydroxyl radicals,
      having been proved to be efficient for water decontamination among various forms
      of electrical discharge systems. The detection and quantification methods of
      these oxygen species in non-thermal plasmas have been reviewed. However, their
      application in dielectric barrier discharge has not been well studied. It is
      therefore imperative to summarise the various detection and quantification
      methods for oxygen-based species determination in AOPs, aqueous systems and non
      thermal plasma processes. Thereafter, reviewed methods are suggested for the
      determination of ROS in DBD configurations to understand the consumption trend of
      these oxidants during treatment of water effluents and to evaluate the
      performance of the treatment reactor configuration towards the degradation of
      targeted pollutants.

PMID- 29446029
TI  - Using network to enhance the insights on correlation and pollution assessment of
      co-occurring metals in marine sediments, the East China Sea.
AB  - In this study, sediment samples were collected from 24 sites in the East China
      Sea (ECS) to investigate the distribution characteristics, co-occurrence
      correlations, and ecological risks of metals. In surface sediments, metals
      presented a homologous banding distribution pattern decreasing seaward with
      distance. With network analysis, it indicated metals in this area might directly
      derive from the coastal river inputs. According to geo-accumulation indexes
      (Igeo), Cd was classified as moderate pollution at 58% sites, far above other
      metals. In addition, the potential ecological risk index (RI) was clustered with
      the ecological risk (ER) of Cd, which was regarded as considerable or high-risk
      level for most coastal stations. Thus Cd pollution in the ESC sediment should be
      paid more attention. In sum, the visualization of statistical analyses combined
      with geochemical approaches could reveal the potential sources of contaminants
      and ecological risks, thus facilitate the pollution evaluation in marine
      sediments.

PMID- 29446030
TI  - Slow progression of renal failure in a child with infantile cystinosis.
AB  - Cystinosis is a rare autosomal recessive lysosomal transport disorder,
      characterized by the accumulation of the aminoacid cystine and progressive
      dysfunction of several organs. Kidneys are severely affected, and the most
      frequent form, infantile nephropathic cystinosis, presents with growth failure in
      infancy, renal Fanconi syndrome and end-stage renal disease by the first decade
      of life. We report of a girl with infantile nephropathic cystinosis that has
      reached adolescence without the need of renal replacement therapy and without
      extrarenal manifestations despite her delayed diagnosis and treatment initiation.
      The girl with this intermediate phenotype was found to have compound
      heterozygosity of one known (1015G > A) and one novel (587_588insA) mutation in
      CTNS gene. Our case points to the wide clinical presentation of infantile
      nephropathic cystinosis and suggest that long-term outcome is not always ominous
      as generally thought.

PMID- 29446031
TI  - Correction to: Injuries in Field Hockey Players: A Systematic Review.
AB  - Page 1: The listing of the author names and affiliations, which previously read.

PMID- 29446032
TI  - Attention-deficit/hyperactivity disorder, joint hypermobility-related disorders
      and pain: expanding body-mind connections to the developmental age.
AB  - Attention-deficit/hyperactivity disorder (ADHD) and generalized joint
      hypermobility (JH) are two separated conditions, assessed, and managed by
      different specialists without overlapping interests. Recently, some researchers
      highlighted an unexpected association between these two clinical entities. This
      happens in a scenario of increasing awareness on the protean detrimental effects
      that congenital anomalies of the connective tissue may have on human health and
      development. To review pertinent literature to identify possible connections
      between ADHD and GJH, special emphasis was put on musculoskeletal pain and
      syndromic presentations of GJH, particularly the hypermobile Ehlers-Danlos
      syndrome. A comprehensive search of scientific databases and references lists was
      conducted, encompassing publications based on qualitative and quantitative
      research. Impaired coordination and proprioception, fatigue, chronic pain, and
      dysautonomia are identified as potential bridges between ADHD and JH. Based on
      these findings, a map of the pathophysiological and psychopathological pathways
      connecting both conditions is proposed. Although ADHD and JH are traditionally
      separated human attributes, their association may testify for the dyadic nature
      of mind-body connections during critical periods of post-natal development. Such
      a mixed picture has potentially important consequences in terms of disability and
      deserves more clinical and research attention.

PMID- 29446033
TI  - Climate Change, Foodborne Pathogens and Illness in Higher-Income Countries.
AB  - PURPOSE OF REVIEW: We present a review of the likely consequences of climate
      change for foodborne pathogens and associated human illness in higher-income
      countries. RECENT FINDINGS: The relationships between climate and food are
      complex and hence the impacts of climate change uncertain. This makes it
      difficult to know which foodborne pathogens will be most affected, what the
      specific effects will be, and on what timescales changes might occur. Hence, a
      focus upon current capacity and adaptation potential against foodborne pathogens
      is essential. We highlight a number of developments that may enhance preparedness
      for climate change. These include the following: Adoption of novel surveillance
      methods, such as syndromic methods, to speed up detection and increase the
      fidelity of intervention in foodborne outbreaks Genotype-based approaches to
      surveillance of food pathogens to enhance spatiotemporal resolution in tracing
      and tracking of illness Ever increasing integration of plant, animal and human
      surveillance systems, One Health, to maximise potential for identifying threats
      Increased commitment to cross-border (global) information initiatives (including
      big data) Improved clarity regarding the governance of complex societal issues
      such as the conflict between food safety and food waste Strong user-centric
      (social) communications strategies to engage diverse stakeholder groups The
      impact of climate change upon foodborne pathogens and associated illness is
      uncertain. This emphasises the need to enhance current capacity and adaptation
      potential against foodborne illness. A range of developments are explored in this
      paper to enhance preparedness.

PMID- 29446034
TI  - Molecular genetic diversity of Gongylonema neoplasticum (Fibiger & Ditlevsen,
      1914) (Spirurida: Gongylonematidae) from rodents in Southeast Asia.
AB  - More than a dozen Gongylonema spp. (Spirurida: Spiruroidea: Gongylonematidae)
      have been described from a variety of rodent hosts worldwide. Gongylonema
      neoplasticum (Fibiger & Ditlevsen, 1914), which dwells in the gastric mucosa of
      rats such as Rattus norvegicus (Berkenhout) and Rattus rattus (Linnaeus), is
      currently regarded as a cosmopolitan nematode in accordance with global
      dispersion of its definitive hosts beyond Asia. To facilitate the reliable
      specific differentiation of local rodent Gongylonema spp. from the cosmopolitan
      congener, the genetic characterisation of G. neoplasticum from Asian Rattus spp.
      in the original endemic area should be considered since the morphological
      identification of Gongylonema spp. is often difficult due to variations of
      critical phenotypical characters, e.g. spicule lengths and numbers of caudal
      papillae. In the present study, morphologically identified G. neoplasticum from
      114 rats of seven species from Southeast Asia were selected from archived survey
      materials from almost 4,500 rodents: Thailand (58 rats), Cambodia (52 rats), Laos
      (three rats) and Philippines (one rat). In addition, several specimens from four
      rats in Indonesia were used in the study. Nucleotide sequences of the ribosomal
      RNA gene (rDNA) (5,649 bp) and the cytochrome c oxidase subunit 1 gene (cox1)
      (818 bp) were characterised. The rDNA showed little nucleotide variation,
      including the internal transcribed spacer (ITS) regions. The cox1 showed 24
      haplotypes, with up to 15 (1.83%) nucleotide substitutions regardless of parasite
      origin. Considering that Rattus spp. have been shown to originate from the
      southern region of Asia and G. neoplasticum is their endogenous parasite, it is
      reasonable to propose that the present study covers a wide spectrum of the
      genetic diversity of G. neoplasticum, useful for both the molecular genetic
      speculation of the species and the molecular genetic differentiation of other
      local rodent Gongylonema spp. from the cosmopolitan congener.

PMID- 29446035
TI  - Sorting Through the Safety Data Haystack: Using Machine Learning to Identify
      Individual Case Safety Reports in Social-Digital Media.
AB  - INTRODUCTION: There is increasing interest in social digital media (SDM) as a
      data source for pharmacovigilance activities; however, SDM is considered a low
      information content data source for safety data. Given that pharmacovigilance
      itself operates in a high-noise, lower-validity environment without objective
      'gold standards' beyond process definitions, the introduction of large volumes of
      SDM into the pharmacovigilance workflow has the potential to exacerbate issues
      with limited manual resources to perform adverse event identification and
      processing. Recent advances in medical informatics have resulted in methods for
      developing programs which can assist human experts in the detection of valid
      individual case safety reports (ICSRs) within SDM. OBJECTIVE: In this study, we
      developed rule-based and machine learning (ML) models for classifying ICSRs from
      SDM and compared their performance with that of human pharmacovigilance experts.
      METHODS: We used a random sampling from a collection of 311,189 SDM posts that
      mentioned Roche products and brands in combination with common medical and
      scientific terms sourced from Twitter, Tumblr, Facebook, and a spectrum of news
      media blogs to develop and evaluate three iterations of an automated ICSR
      classifier. The ICSR classifier models consisted of sub-components to annotate
      the relevant ICSR elements and a component to make the final decision on the
      validity of the ICSR. Agreement with human pharmacovigilance experts was chosen
      as the preferred performance metric and was evaluated by calculating the Gwet AC1
      statistic (gKappa). The best performing model was tested against the Roche global
      pharmacovigilance expert using a blind dataset and put through a time test of the
      full 311,189-post dataset. RESULTS: During this effort, the initial strict rule
      based approach to ICSR classification resulted in a model with an accuracy of 65%
      and a gKappa of 46%. Adding an ML-based adverse event annotator improved the
      accuracy to 74% and gKappa to 60%. This was further improved by the addition of
      an additional ML ICSR detector. On a blind test set of 2500 posts, the final
      model demonstrated a gKappa of 78% and an accuracy of 83%. In the time test, it
      took the final model 48 h to complete a task that would have taken an estimated
      44,000 h for human experts to perform. CONCLUSION: The results of this study
      indicate that an effective and scalable solution to the challenge of ICSR
      detection in SDM includes a workflow using an automated ML classifier to identify
      likely ICSRs for further human SME review.

PMID- 29446036
TI  - Mindfulness Approaches and Weight Loss, Weight Maintenance, and Weight Regain.
AB  - PURPOSE OF REVIEW: There is an urgent need for effective weight management
      techniques, as more than one third of US adults are overweight or obese.
      Recommendations for weight loss include a combination of reducing caloric intake,
      increasing physical activity, and behavior modification. Behavior modification
      includes mindful eating or eating with awareness. The purpose of this review was
      to summarize the literature and examine the impact of mindful eating on weight
      management. RECENT FINDINGS: The practice of mindful eating has been applied to
      the reduction of food cravings, portion control, body mass index, and body
      weight. Past reviews evaluating the relationship between mindfulness and weight
      management did not focus on change in mindful eating as the primary outcome or
      mindful eating as a measured variable. This review demonstrates strong support
      for inclusion of mindful eating as a component of weight management programs and
      may provide substantial benefit to the treatment of overweight and obesity.

PMID- 29446038
TI  - Preoperative evaluation of the elderly surgical patient and anesthesia challenges
      in the XXI century.
AB  - Universally recognized goals of preoperative anesthesia assessment are the
      evaluation of patient's health status to define the entity of the surgical risk,
      and the anticipation of possible complications while optimizing and planning
      preventive strategies. Data obtained by Comprehensive Geriatric Assessment (CGA)
      and frailty evaluation are of extreme usefulness in surgical risk evaluation in
      older patients and in the decision about surgery. It is from the team-based
      discussion of such results that the most appropriate treatment can be
      individuated, surgery invasiveness and duration critically analyzed and if needed
      modified, and the best perioperative strategy carefully tailored. These data
      should thus be used as reference points not only in preoperative assessment but
      also in planning the perioperative course, from pre-habilitation to adequate
      intraoperative management to complications prevention and care continuity after
      discharge. It is from such a far-seeing approach that issues emerged from
      preoperative evaluation can really contribute to decision-making about surgery in
      the elderly.

PMID- 29446037
TI  - Developing Healthy Food Preferences in Preschool Children Through Taste Exposure,
      Sensory Learning, and Nutrition Education.
AB  - PURPOSE OF REVIEW: The present review was undertaken in order to summarize and
      evaluate recent research investigating taste exposure, sensory learning, and
      nutrition education interventions for promoting vegetable intake in preschool
      children. RECENT FINDINGS: Overall, taste exposure interventions yielded the best
      outcomes for increasing vegetable intake in early childhood. Evidence from
      sensory learning strategies such as visual exposure and experiential learning
      also show some success. While nutrition education remains the most common
      approach used in preschool settings, additional elements are needed to strengthen
      the educational program for increasing vegetable intake. There is a substantial
      gap in the evidence base to promote vegetable intake in food fussy children. The
      present review reveals the relative importance of different intervention
      strategies for promoting vegetable intake. To strengthen intervention effects for
      improving vegetable intake in preschool children, future research could consider
      integrating taste exposure and sensory learning strategies with nutrition
      education within the preschool curriculum.

PMID- 29446039
TI  - ADHD-juvenile bipolar disorder: mimics and chameleons!

PMID- 29446040
TI  - Significance of continuous rotavirus and norovirus surveillance in Indonesia.
AB  - BACKGROUND: Diarrhea significantly contributes to the global burden of diseases,
      particularly in developing countries. Rotavirus and norovirus are the most
      dominant viral agents responsible for diarrheal disease globally. The aim of this
      review was to conduct a comprehensive assessment of rotavirus and norovirus study
      in Indonesia. DATA SOURCES: Articles about rotavirus and norovirus surveillance
      in Indonesia were collected from databases, including PubMed and Google Scholar.
      Manual searching was performed to identify additional studies. Furthermore,
      relevant articles about norovirus diseases were included. RESULTS: A national
      surveillance of rotavirus-associated gastroenteritis has been conducted for
      years, resulting in substantial evidence about the high burden of the diseases in
      Indonesia. In contrast, norovirus infection received relatively lower attention
      and very limited data are available about the incidence and circulating
      genotypes. Norovirus causes sporadic and epidemic gastroenteritis globally. It is
      also emerging as a health problem in immunocompromised individuals. During post
      rotavirus vaccination era, norovirus potentially emerges as the most frequent
      cause of diarrheal diseases. CONCLUSIONS: Our review identifies knowledge gaps in
      Indonesia about the burden of norovirus diseases and the circulating genotypes.
      Therefore, there is a pressing need to conduct national surveillance to raise
      awareness of the community and national health authority about the actual burden
      of norovirus disease in Indonesia. Continuing rotavirus surveillance is also
      important to assess vaccine effectiveness and to continue tracking any
      substantial changes of circulating rotavirus genotypes.

PMID- 29446041
TI  - Characteristic findings of high-grade cervical intraepithelial neoplasia or more
      on magnifying endoscopy with narrow band imaging.
AB  - BACKGROUND: Colposcopy, which is a standard modality for diagnosing cervical
      intraepithelial neoplasia (CIN), can have limited accuracy owing to poor
      visibility. Flexible magnifying endoscopy with narrow band imaging (ME-NBI) has
      excellent diagnostic accuracy for early gastrointestinal neoplasms and is
      expected to be highly useful for CIN diagnosis. This study aimed to determine the
      characteristic findings and evaluate the diagnostic ability of ME-NBI for lesions
      >= CIN 3. METHODS: A well-designed prospective diagnostic case series conducted
      at multiple tertiary-care centers. A total of 24 patients who underwent cervical
      conization with a preoperative diagnosis of high-grade squamous cell
      intraepithelial lesions (HSILs) or lesions >= CIN 3 were enrolled. Prior to
      conization, still images and video of ME-NBI were captured to investigate the
      cervical lesions. The images were reviewed based on histological examination of
      the resected specimens. RESULTS: The NBI-ME images revealed the following
      abnormal findings: (1) light white epithelium (l-WE), (2) heavy white epithelium
      (h-WE), and (3) atypical intra-epithelial papillary capillary loop (IPCL).
      Pathological examination of the resected specimens confirmed cervical lesions >=
      CIN 3 in 21 patients. The ME-NBI findings were classified into four groups: l-WE,
      l-WE with atypical IPCL, h-WE, and h-WE with atypical IPCL, at rates of 0, 23.8,
      9.5, and 66.7%, respectively. Additionally, all 3 patients with micro-invasive
      carcinoma showed a strong irregularity of IPCLs. CONCLUSION: The lesions >= CIN 3
      demonstrated characteristic ME-NBI findings of h-WE alone, or l-/h-WE with
      atypical micro-vessels. This study indicates that ME-NBI may have novel value for
      CIN diagnosis.

PMID- 29446042
TI  - The clinical features of squamous cell lung carcinoma with sensitive EGFR
      mutations.
AB  - BACKGROUND: The process of selecting patients on the basis of epidermal growth
      factor receptor (EGFR) mutations would likely result in a patient population with
      greater sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, EGFR
      mutation status is not routinely examined in patients with squamous cell lung
      cancer (Sq) because of the low incidence of EGFR mutations and the poor clinical
      response to EGFR-TKIs. METHODS: We retrospectively reviewed the clinical features
      of patients at our hospital with Sq who carried EGFR-TKI-sensitive EGFR mutations
      and assessed their responses to EGFR-TKIs. RESULTS: EGFR mutation status was
      tested in 23 of 441 patients with Sq (5.2%) admitted to our hospital during the
      study period. An EGFR mutation (exon 19 deletion 3, L858R 2) was identified in
      five of the 23 patients (21.7%), all of whom were female never-smokers. Of these
      five patients, four (4/9; 44.4%) were in the normal lung group, one (1/12; 8.3%)
      was in the emphysematous lung group, and none (0/2; 0%) in the fibrotic lung
      group. Two of these five patients with the EGFR mutation received gefitinib and
      two received afatinib. Although the two patients who were treated with gefitinib
      did not respond well to treatment (stable disease, 1 patient; progressive
      disease, 1 patient), the two patients who were treated with afatinib showed a
      good response (partial response, 2 patients). CONCLUSION: The administration of
      afatinib to Sq patients after selecting patients using the EGFR mutation test
      based on their underlying pulmonary disease and smoking status would likely
      result in a population with a greater sensitivity to afatinib.

PMID- 29446043
TI  - Long-term outcomes of postoperative taxane/platinum chemotherapy for early stage
      cervical cancer: a retrospective study.
AB  - BACKGROUND: Taxane/platinum (TP)-based combination chemotherapy is standard for
      the treatment of metastatic or recurrent cervical cancer. The aim of this study
      was to investigate the efficacy of postoperative TP therapy in early stage
      cervical cancer. METHODS: A retrospective review of patients with FIGO IB-IIB
      stage cervical cancer who were treated with radical hysterectomy and displayed
      surgical-pathological risk factors was performed. 122 patients were identified
      between 2003 and 2012. Survival was analyzed by Kaplan-Meier method and compared
      by the log-rank test. The Cox proportional hazards model was used to investigate
      predictors of survival. RESULTS: The median follow-up period was 82.4 months. The
      postoperative adjuvant therapy was TP in 82 (67.2%) patients, other
      chemotherapies in 10 (8.2%), radiotherapy (RT) in 25 (20.5%), and no further
      therapy (NFT) in 5 (4.1%). Survival was analyzed using 4 subgroups according to
      the postoperative adjuvant therapy. The estimated 5-year overall survival was
      95.1% in the TP group, 90.0% in the other chemotherapy group, 78.9% in the RT
      group, and 100% in the NFT group. No significant difference of survival was
      observed in the subgroups. However, when analyzing only patients who displayed
      high-risk factors, non-TP adjuvant therapy (including RT and other
      chemotherapies) was independently associated with shorter survival on
      multivariate analysis. In the TP group, multivariate analysis revealed that a
      positive surgical margin was a significant predictor of shorter survival.
      CONCLUSIONS: Postoperative TP is effective in patients with surgically treated
      early stage cervical cancer. In these populations, a positive surgical margin
      could be associated with poor prognosis.

PMID- 29446044
TI  - Electrophysiological correlates of encoding processes in a full-report visual
      working memory paradigm.
AB  - Why are some visual stimuli remembered, whereas others are forgotten? A
      limitation of recognition paradigms is that they measure aggregate behavioral
      performance and/or neural responses to all stimuli presented in a visual working
      memory (VWM) array. To address this limitation, we paired an
      electroencephalography (EEG) frequency-tagging technique with two full-report VWM
      paradigms. This permitted the tracking of individual stimuli as well as the
      aggregate response. We recorded high-density EEG (256 channel) while participants
      viewed four shape stimuli, each flickering at a different frequency. At
      retrieval, participants either recalled the location of all stimuli in any order
      (simultaneous full report) or were cued to report the item in a particular
      location over multiple screen displays (sequential full report). The individual
      frequency tag amplitudes evoked for correctly recalled items were significantly
      larger than the amplitudes of subsequently forgotten stimuli, regardless of
      retrieval task. An induced-power analysis examined the aggregate neural
      correlates of VWM encoding as a function of items correctly recalled. We found
      increased induced power across a large number of electrodes in the theta, alpha,
      and beta frequency bands when more items were successfully recalled. This effect
      was more robust for sequential full report, suggesting that retrieval demands can
      influence encoding processes. These data are consistent with a model in which
      encoding-related resources are directed to a subset of items, rather than a model
      in which resources are allocated evenly across the array. These data extend
      previous work using recognition paradigms and stress the importance of encoding
      in determining later VWM retrieval success.

PMID- 29446045
TI  - Effects of extracellular orotic acid on acute contraction-induced adaptation
      patterns in C2C12 cells.
AB  - Dietary administration of orotic acid (OA), an intermediate in the pyrimidine
      biosynthetic pathway, is considered to provide a wide range of beneficial
      effects, including cardioprotection and exercise adaptation. Its mechanisms of
      action, when applied extracellularly, however, are barely understood. In this
      study, we evaluated potential effects of OA on skeletal muscle using an in vitro
      contraction model of electrically pulse-stimulated (EPS) C2C12 myotubes. By
      analyzing a subset of genes representing inflammatory, metabolic, and structural
      adaptation pathways, we could show that OA supplementation diminishes the EPS
      provoked expression of inflammatory transcripts (interleukin 6, Il6; chemokine (C
      X-C Motif) ligand 5, Cxcl5), and attenuated transcript levels of nuclear receptor
      subfamily 4 group A member 3 (Nr4A3), early growth response 1 (Egr1), activating
      transcription factor 3 (Atf3), and fast-oxidative MyHC-IIA isoform (Myh2). By
      contrast, OA had no suppressive effect on the pathogen-provoked inflammatory gene
      response in skeletal muscle cells, as demonstrated by stimulation of C2C12
      myotubes with bacterial LPS. In addition, we observed a suppressive effect of OA
      on EPS-induced phosphorylation of AMP-activated protein kinase (AMPK), whereas
      EPS-triggered phosphorylation/activation of the mammalian target of rapamycin
      (mTOR) was not affected. Finally, we demonstrate that OA positively influences
      glycogen levels in EP-stimulated myotubes. Taken together, our results suggest
      that in skeletal muscle cells, OA modulates both the inflammatory and the
      metabolic reaction provoked by acute contraction. These results might have
      important clinical implications, specifically in cardiovascular and exercise
      medicine.

PMID- 29446046
TI  - Anti-neovascularization effects of DMBT in age-related macular degeneration by
      inhibition of VEGF secretion through ROS-dependent signaling pathway.
AB  - Choroidal neovascularization (CNV) is the hallmark of late-staged wet age-related
      macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a key
      component in the development and progression of wet AMD. DMBT, 6,6'-bis(2,3
      dimethoxybenzoyl)-alpha,alpha-D-trehalose, had been proved that it could suppress
      tumor angiogenesis and metastasis by inhibiting production of VEGF. But the
      effects of DMBT on CNV were not known. This study was to investigate effects and
      mechanisms of DMBT on CNV in vitro and in vivo. Results showed that DMBT could
      inhibit migration and tube formation of RF/6A cells under ARPE-19 hypoxia
      conditioned medium. DMBT could reduce lesion area in laser-induced CNV model
      mice. ELISA and Western blotting assay showed that DMBT markedly inhibited
      secretion of VEGF in vitro and in vivo. Furthermore, DMBT restrained ROS level
      under hypoxia via suppressing Nrf2/HO-1 pathway. DMBT effectively suppressed
      hypoxia-induced the up-regulation of p-Akt, p-NF-kappaB, and HIF-1alpha. These
      results suggest that DMBT can inhibit CNV by down-regulation of VEGF in retina
      through Akt/NF-kappaB/HIF-1alpha and ERK/Nrf2/HO-1/HIF-1alpha pathway. DMBT might
      be a promising lead molecule for anti-CNV and serve as a therapeutic agent to
      inhibit CNV.

PMID- 29446047
TI  - Epigallocatechin gallate suppresses hepatic cholesterol synthesis by targeting
      SREBP-2 through SIRT1/FOXO1 signaling pathway.
AB  - This study aims to explore the effect of epigallocatechin gallate (EGCG) on blood
      lipids, liver lipids, and cholesterol synthesis in hyperlipidemic rats. SREBP-2
      transgenic rats were used to investigate the transcriptional level of SREBP-2
      regulated by SIRT-1/FOXO1 and the molecular mechanism of rate-limiting enzyme
      HMGCR that affects cholesterol synthesis. Rat models of hyperlipidemia were
      established and administered EGCG. Cholesterol synthesis was observed. Enzyme
      linked immunosorbent assay was used to determine serum triglyceride (TG), total
      cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C), free fatty acid (FFA), superoxide dismutase
      (SOD), malondialdehyde (MDA), and T-AOC contents. Hematoxylin-eosin staining and
      oil red O staining were utilized to observe the histological changes in the
      liver. Biochemical method was applied to measure serum ALT and AST changes.
      Western blot assay and qRT-PCR were employed to detect the changes in SIRT1/FOXO1
      pathway-related proteins, cholesterol synthesis-related genes, and SREBP-2. EGCG
      50 mg/kg could obviously decrease the liver weight and liver coefficient, reduce
      serum TG, TC, LDL-C, and FFA levels (P < 0.05), and increase serum HDL-C levels
      in hyperlipidemic rats. EGCG could diminish hyperlipidemia-induced liver injury
      and reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) levels. Oil red O staining results demonstrated that the number of red
      lipid droplets in hepatocytes reduced to varying degrees, especially high-dose
      EGCG. EGCG remarkably diminished MDA content in the liver with
      hypercholesterolemia and increased T-AOC and SOD activity. In the model group,
      SIRT1 expression increased, and FOXO1 expression decreased. EGCG activated SIRT1
      and increased FOXO1 expression, whose expression trend was consistent with the
      fenofibrate group. HMGCR, FDPS, SS, and ABCA1 expression increased, and ACAT2
      expression noticeably reduced in SREBP-2+/+ transgenic rats. EGCG could reverse
      the expression trend of each gene. Simultaneously, EGCG increased FOXO1
      expression, and decrease SREBP-2 expression; however, no significant changes in
      these expression were found in SREBP-2-/- rats. EGCG can alleviate liver injury
      and oxidative stress in hyperlipidemic rats. EGCG can activate SIRT1, activate
      FOXO1 protein, regulate SREBP-2 protein, and inhibit hepatic cholesterol
      synthesis.

PMID- 29446049
TI  - ?

PMID- 29446048
TI  - Adiponectin and colon cancer: evidence for inhibitory effects on viability and
      migration of human colorectal cell lines.
AB  - Adiponectin (Acrp30) is an adipokine widely studied for its beneficial metabolic
      and anti-inflammatory properties. Colorectal cancer is among the most common
      cancers worldwide. The aim of present study was to explore the effects of Acrp30
      on both CaCo-2 and HCT116 colorectal cancer cells in terms of viability,
      oxidative stress, and apoptosis. In addition, since colorectal cancer represents
      a typical inflammation-related cancer, we investigated whether Acrp30 treatment
      modifies the migration and the expression of crucial proteins in the EMT
      transition. Finally, we analyzed the expression of cytokines in CaCo-2 cells. We
      found that Acrp30 reduces the survival rate of both CaCo-2 and HCT116 cells
      through induction of apoptosis and oxidative stress already after 24 h of
      treatment. In addition, wound-healing assay indicated that Acrp30 exposure
      statistically inhibits CaCo-2 and HCT116 cell migration. Western blot analysis
      performed on E-cadherin and vimentin, two EMT crucial markers in carcinogenesis,
      indicated that Acrp30 does not influence EMT transition. Finally, we found a
      reduction of mRNA levels corresponding to the anti-inflammatory IL-10 cytokine
      together with an increase of the pro-inflammatory IL-6 and IL-8 cytokines. This
      study provides new insight into Acrp30 molecular effects on colorectal cancer
      cells. Indeed, even if further studies are necessary to clarify the precise role
      of Acrp30 in colorectal cancer, our data strongly suggest that Acrp30 negatively
      regulates cell survival and migration in association with induction of oxidative
      stress and regulation of cytokines expression in both CaCo-2 and HCT116
      colorectal cells.

PMID- 29446050
TI  - Coping Mechanisms for Psychosomatic Symptoms among Aging Roman Catholic German
      priests.
AB  - To identify and investigate coping mechanisms and other factors which may impact
      upon the psychosomatic symptoms of aging German Roman Catholic priests. A cross
      sectional study was conducted among 499 aging German Roman Catholic priests with
      standardized questionnaires: Brief Symptom Inventory, Coping Inventory Stressful
      Situations, and Religious Coping Scale. Task-Oriented Coping exhibited a
      significant difference between the two groups. Multiple regression analyses
      indicated that psychosomatic symptoms could be best predicted by means of Task
      Oriented Coping mechanisms, identification with priesthood, and by a low Negative
      Religious Coping. The success of adaptive coping processes for older clergy may
      depend on how they employ strategies, strengthen their spiritual dimensions, and
      manage important psychosocial aspects of aging. In our sample, Depression and
      Somatization are explained best by Emotion-Oriented Coping. It is desirable for
      aging priests to be aware of protective factors like Role Identification, Task
      Oriented Coping, and low Negative Religious Coping, which may be helpful in
      improving their psychological well-being.

PMID- 29446051
TI  - Face and content validity of Xperience Team Trainer: bed-side assistant training
      simulator for robotic surgery.

PMID- 29446052
TI  - Correction to: PK-PD Compass: bringing infectious diseases pharmacometrics to the
      patient's bedside.
AB  - The original version of this article contained incorrect Supplementary Files. The
      correct Supplementary Files are published with this erratum.

PMID- 29446054
TI  - Upregulation of Pro-inflammatory Cytokine Expression Following Chronic
      Paracetamol Treatment in Astrocyte.
AB  - The present study aimed to investigate the effect of APAP treatment on the
      expression of pro-inflammatory cytokines in the astrocytes. The mouse astrocyte
      cells (C8-D1A) were treated with APAP at the concentration of 100 MUM for 24 h,
      16 and 28 days. The expressions of pro-inflammatory cytokines and NF-kB were
      determined using western blot analysis. Furthermore, the expression and
      localization of phosphorylation of NF-kB were detected by immunohistochemical and
      immunofluorescent analysis. The ultrastructure of C8-D1A cells was as well
      monitored. The results revealed that acute APAP treatment (24 h) had no effect on
      the expression of pro-inflammatory cytokines and pNF-kB. This treatment did not
      alter the ultrastructure of C8-D1A cells when compared with those in the control
      cells. However, the results obtained from the study on chronic APAP-treated cells
      (16 and 28 days) showed the different effect of APAP treatment. The results
      obtained from western blot analysis showed the increment of pro-inflammatory
      cytokine (IL-1beta and TNF-alpha) expressions and the activation of NF-kB
      signaling pathway. Nuclear translocation of pNF-kB and alteration of several cell
      structures were well observed in the C8-D1A cells with chronic APAP treatment.
      The results obtained from this study suggest that chronic APAP treatment can
      induce an upregulation of pro-inflammatory cytokines (IL-1beta and TNFalpha) in
      astrocytes. This alteration implies the involvement of the activation of NF-kB
      signaling pathway.

PMID- 29446053
TI  - Systems pharmacological analysis of mitochondrial cardiotoxicity induced by
      selected tyrosine kinase inhibitors.
AB  - Tyrosine kinase inhibitors (TKIs) are targeted therapies rapidly becoming favored
      over conventional cytotoxic chemotherapeutics. Our study investigates two FDA
      approved TKIs, DASATINIB; indicated for IMATINIB-refractory chronic myeloid
      leukemia, and SORAFENIB; indicated for hepatocellular carcinoma and advanced
      renal cell carcinoma. Limited but crucial evidence suggests that these agents can
      have cardiotoxic side effects ranging from hypertension to heart failure. A
      greater understanding of the underlying mechanisms of this cardiotoxicity are
      needed as concerns grow and the capacity to anticipate them is lacking. The
      objective of this study was to explore the mitochondrial-mediated cardiotoxic
      mechanisms of the two selected TKIs. This was achieved experimentally using
      immortalized human cardiomyocytes, AC16 cells, to investigate dose- and time
      dependent cell killing, along with measurements of temporal changes in key
      signaling proteins involved in the intrinsic apoptotic and autophagy pathways
      upon exposure to these agents. Quantitative systems pharmacology (QSP) models
      were developed to capture the toxicological response in AC16 cells using protein
      dynamic data. The developed QSP models captured well all the various trends in
      protein signaling and cellular responses with good precision on the parameter
      estimates, and were successfully qualified using external data sets. An interplay
      between the apoptotic and autophagic pathways was identified to play a major role
      in determining toxicity associated with the investigated TKIs. The established
      modeling platform showed utility in elucidating the mechanisms of cardiotoxicity
      of SORAFENIB and DASATINIB. It may be useful for other small molecule targeted
      therapies demonstrating cardiac toxicities, and may aid in informing alternate
      dosing strategies to alleviate cardiotoxicity associated with these therapies.

PMID- 29446055
TI  - Which Costs Matter? Costs Included in Economic Evaluation and their Impact on
      Decision Uncertainty for Stable Coronary Artery Disease.
AB  - BACKGROUND: Variation exists in the resource categories included in economic
      evaluations, and National Institute for Health and Care Excellence (NICE)
      guidance suggests the inclusion only of costs related to the index condition or
      intervention. However, there is a growing consensus that all healthcare costs
      should be included in economic evaluations for Health Technology Assessments
      (HTAs), particularly those related to extended years of life. OBJECTIVE AND
      METHODS: We aimed to quantify the impact of a range of cost categories on the
      adoption decision about a hypothetical intervention, and uncertainty around that
      decision, for stable coronary artery disease (SCAD) based on a dataset comprising
      94,966 patients. Three costing scenarios were considered: coronary heart disease
      (CHD) costs only, cardiovascular disease (CVD) costs and all costs. The first two
      illustrate different interpretations of what might be regarded as related costs.
      RESULTS: Employing a 20-year time horizon, the highest mean expected incremental
      cost was when all costs were included (L2468) and the lowest when CVD costs only
      were included (L2377). The probability of the treatment being cost effective,
      estimating health opportunity costs using a ratio of L30,000 per quality-adjusted
      life-year (QALY), was different for each of the CHD (70%) costs, CVD costs (73%)
      and all costs (56%) scenarios. The results concern a hypothetical intervention
      and are illustrative only, as such they cannot necessarily be generalised to all
      interventions and diseases. CONCLUSIONS: Cost categories included in an economic
      evaluation of SCAD impact on estimates of both cost effectiveness and decision
      uncertainty. With an aging and co-morbid population, the inclusion of all
      healthcare costs may have important ramifications for the selection of healthcare
      provision on economic grounds.

PMID- 29446057
TI  - In Vitro Evaluation of Probiotic Potential of Lactic Acid Bacteria Isolated from
      Yunnan De'ang Pickled Tea.
AB  - This study aimed to investigate the probiotic potential of lactic acid bacteria
      (LAB) strains isolated from De'ang pickled tea, a traditional food consumed by
      the De'ang nationality of Yunnan, China. Twenty-six LAB strains isolated from
      De'ang pickled tea were subjected to identification based on 16S rRNA gene
      sequence analysis. Twenty-four belonged to Lactobacillus plantarum, one belonged
      to Enterococcus casseliflavus, and one belonged to Lactobacillus acidophilus.
      Eighteen out of 26 LAB strains which showed a higher capability to tolerate
      simulated gastrointestinal juices were chosen to further evaluate their probiotic
      properties. Varied adhesive abilities and auto-aggregative capacities of selected
      LAB strains were dependent on species and even strains. All tested LAB strains
      were resistant to kanamycin, streptomycin, gentamycin, and vancomycin and
      sensitive to tetracycline and chloramphenicol. Ten out of the 18 strains are
      resistant to ampicillin, and the remaining strains are sensitive to ampicillin; 4
      out of the 18 strains showed resistance to erythromycin. Compared to reference
      strain Lactobacillus rhamnosus strain GG, these LAB strains had a greater or
      comparative antimicrobial activity against Salmonella typhimurium or Escherichia
      coli. In contrast, eight out of the 18 strains suppressed growth of Shigella
      flexneri. Two L. plantarum strains, ST and STDA10, not only exhibited good
      probiotic properties but also showed a good ability of scavenging DPPH and ABTS+.
      This study suggests that L. plantarum ST and STDA10 could be used as potential
      probiotics applied in functional foods.

PMID- 29446056
TI  - Hypothesis: structural heterogeneity of the unfolded proteins originating from
      the coupling of the local clusters and the long-range distance distribution.
AB  - We propose a hypothesis that explains two apparently contradicting observations
      for the heterogeneity of the unfolded proteins. First, the line confocal method
      of the single-molecule Forster resonance energy transfer (sm-FRET) spectroscopy
      revealed that the unfolded proteins possess broad peaks in the FRET efficiency
      plot, implying the significant heterogeneity that lasts longer than milliseconds.
      Second, the fluorescence correlation method demonstrated that the unfolded
      proteins fluctuate in the time scale shorter than 100 ns. To formulate the
      hypothesis, we first summarize the recent consensus for the structure and
      dynamics of the unfolded proteins. We next discuss the conventional method of the
      sm-FRET spectroscopy and its limitations for the analysis of the unfolded
      proteins, followed by the advantages of the line confocal method that revealed
      the heterogeneity. Finally, we propose that the structural heterogeneity formed
      by the local clustering of hydrophobic residues modulates the distribution of the
      long-range distance between the labeled chromophores, resulting in the broadening
      of the peak in the FRET efficiency plot. A clustering of hydrophobic residues
      around the chromophore might further contribute to the broadening. The proposed
      clusters are important for the understanding of protein folding mechanism.

PMID- 29446058
TI  - Erratum to: Bacterial Filamentous Appendages Investigated by Solid-State NMR
      Spectroscopy.

PMID- 29446059
TI  - The novel involvement of podocyte autophagic activity in the pathogenesis of
      lupus nephritis.
AB  - BACKGROUND: Lupus nephritis (LN) is one of the most common and severe
      complications in Systemic lupus erythematosus patients, and the mechanism
      underlining the pathogenesis of LN is still unknown. Autophagy plays vital roles
      in maintaining cell homeostasis and is involved in the pathogenesis of many
      diseases. In this study, we investigated the role of autophagy in the progression
      of LN. METHODS: Autophagic activities in podocytes of both LN patients (Class IV
      and V) and mice were evaluated. Podocytes were observed by electron microscopy,
      and autophagic activity was evaluated by immunofluorescence staining and western
      blot analysis. Apoptotic activity was evaluated by immunohistochemistry, TUNEL
      assays and flow cytometric analysis. RESULTS: Significantly greater podocyte
      injury and discrepant autophagic levels were observed in LN patients.
      Differentiated mouse podocytes in the LN group showed reduced nephrin expression
      and increased apoptosis, as well as significantly higher levels of apoptosis
      related proteins (cleaved caspase-3 and Bax). In the mice LN group, the increased
      number of autophagosomes was accompanied by increased LC3-II/LC3-I ratios and
      decreased p62, suggesting increased autophagic and apoptotic activity in
      podocytes. Blockade of autophagic activity by 3-MA or siRNA-mediated silencing of
      Atg5 resulted in decreases in LC3-II/LC3-I ratios, podocyte apoptosis and damage
      in the mice LN group. Futhermore, Rapamycin treatment increased LC3-II/LC3-I
      ratios, and enhanced LN-induced apoptosis in podocyte from modal animal.
      CONCLUSIONS: This study demonstrates that autophagic activity of podocytes is a
      crucial factor in renal injury by directly affecting the function of podocyte;
      thus, inhibiting this activity during the early stages of LN is implicated as a
      potential therapeutic strategy for delaying the progression of LN. Also, clinical
      application in LN needs to consider patients' pathological type and drugs'
      comprehensive effectiveness.

PMID- 29446060
TI  - Effect of adding midazolam to bupivacaine during rectus sheath block: a
      randomised controlled trial.
AB  - BACKGROUND: Various adjuvants have been tried to improve quality and increase
      duration of local anaesthetics during various nerve blocks. We aimed to evaluate
      the effect of adding midazolam to bupivacaine on rectus sheath (RS) block in
      patients undergoing umbilical or epigastric hernia repair. METHODS: In all, 60
      adult patients were divided into two equal groups, each group included 30
      patients. Group I received 20 ml of bupivacaine hydrochloride 0.25% + midazolam
      50 MUg/kg in 2 ml saline 0.9% (Midazolam group, n = 30), whereas Group II
      received 20 ml of bupivacaine hydrochloride 0.25% + 2 ml saline (Control group, n
      = 30) for RS block on each side. The primary outcome was post-operative 48 h
      morphine consumption, whereas secondary outcomes included analgesia duration,
      post-operative pain, as evaluated by visual analogue scale (VAS) for pain scoring
      at 1, 2, 6, 12, 24 and 48 h post-operatively, reported post-operative nausea and
      or vomiting (PONV), somnolence or any adverse drug reactions. RESULTS: The
      current study showed that addition of midazolam to bupivacaine for RS blockade
      provided good analgesia as evidenced by a statistically significant less morphine
      consumption in the post-operative 48 h [11.2 (5.3-18.3) vs. 25.9 (15.2-31.0) mg,
      P = 0.002], longer duration of analgesia, lower VAS during post-operative 48 h,
      lower incidence of PONV, somnolence and pruritus. CONCLUSION: Midazolam addition
      to bupivacaine for RS blockade provided adjuvant analgesia as supported by less
      morphine consumption, longer duration of analgesia, and lower VAS score.

PMID- 29446061
TI  - Viewpoints of dentists on the use of bisphosphonates in rheumatology patients.
AB  - OBJECTIVES: Alhough typically prescribed in oncology, bisphosphonates (BPs) are
      also employed in rheumatology, particularly for the treatment of osteoporosis,
      sometimes resulting in complications, such as osteonecrosis of the jaw. Because
      of different opinions between rheumatologists and dentists on BP use, this study
      aimed to assess the views of dentists regarding administration of BPs in
      rheumatology. METHODS: A questionnaire was sent to 880 dentists from the Auvergne
      region of France to determine their views on BP treatment. RESULTS: We obtained
      382 (43.4%) responses and analysed 376 (58.7% men). In total, 156 (41.5%) of the
      responders analysed had attended an in-service training course (ISTC) on the
      topic. A total of 237 (63.0%) systematically inquired as to whether their
      patients were undergoing BP treatment; this proportion was higher among those who
      had been practicing for fewer than 10 years (P < 0.004). For patients receiving
      BPs, 84.5% of practitioners felt ill at ease about performing dental surgery (n =
      318) and 11% felt ill at ease about performing nonsurgical dental care (n = 41);
      67% stated that their practice differed depending on the method of BP
      administration (per os or intravenously). Overall, 53.7% of practitioners felt
      uncomfortable when asked by a rheumatologist whether a given patient's dental
      status permitted prescription of BP (n = 202). This proportion was higher among
      those who had never attended an ISTC (62.6% vs. 50.7%; P < 0.03). CONCLUSIONS:
      Dentists feel ill at ease providing dental surgery to patients receiving BPs.
      Closer collaboration and better information-sharing between rheumatologists and
      dentists is necessary to facilitate the administration of BPs in rheumatology.

PMID- 29446062
TI  - Predicted MHC peptide binding promiscuity explains MHC class I 'hotspots' of
      antigen presentation defined by mass spectrometry eluted ligand data.
AB  - Peptides that bind to and are presented by MHC class I and class II molecules
      collectively make up the immunopeptidome. In the context of vaccine development,
      an understanding of the immunopeptidome is essential, and much effort has been
      dedicated to its accurate and cost-effective identification. Current state-of-the
      art methods mainly comprise in silico tools for predicting MHC binding, which is
      strongly correlated with peptide immunogenicity. However, only a small proportion
      of the peptides that bind to MHC molecules are, in fact, immunogenic, and
      substantial work has been dedicated to uncovering additional determinants of
      peptide immunogenicity. In this context, and in light of recent advancements in
      mass spectrometry (MS), the existence of immunological hotspots has been given
      new life, inciting the hypothesis that hotspots are associated with MHC class I
      peptide immunogenicity. We here introduce a precise terminology for defining
      these hotspots and carry out a systematic analysis of MS and in silico predicted
      hotspots. We find that hotspots defined from MS data are largely captured by
      peptide binding predictions, enabling their replication in silico. This leads us
      to conclude that hotspots, to a great degree, are simply a result of promiscuous
      HLA binding, which disproves the hypothesis that the identification of hotspots
      provides novel information in the context of immunogenic peptide prediction.
      Furthermore, our analyses demonstrate that the signal of ligand processing,
      although present in the MS data, has very low predictive power to discriminate
      between MS and in silico defined hotspots.

PMID- 29446063
TI  - Direct and Indirect Healthcare Resource Utilization and Costs Among Migraine
      Patients in the United States.
AB  - OBJECTIVE: The goal of this analysis was to provide a contemporary estimate of
      the burden of migraine, incorporating both direct and indirect costs, by
      comparing the costs of migraine patients to a matched group of patients without
      migraine in a large, nationally representative sample of commercially insured
      patients in the United States. BACKGROUND: Previous studies have shown that the
      economic burden of migraine in the United States is substantial for payers,
      patients, and employers. Despite the availability of multiple acute and
      preventive pharmacological treatment options and a relatively stable migraine
      prevalence in the United States, there has been a documented increase in migraine
      related healthcare resource and pharmacy use. Given the frequently disabling
      nature of migraine and its high prevalence, especially during peak productive
      years, and the lack of recent estimates of the burden of migraine, there is a
      need to update the existing literature with more current data. METHODS: This
      retrospective, observational cohort study identified migraine patients in the
      Truven Health Market Scan Research Databases between January 2008 and June 2013.
      Adult patients had 12 months of continuous enrollment before (baseline period)
      and after (follow-up period) the day they received migraine diagnoses and/or
      medications (index) and no diagnosis of HIV or malignancy during the study
      period. The patients with migraine were matched 1:1 to a group of patients
      without migraine on demographic variables and index date. Direct healthcare
      utilization and costs and indirect (absenteeism, short-term disability, and long
      term disability) costs were assessed during the 12-month follow-up period and
      differences between patients with vs without migraine were assessed. Two
      additional multivariable logistic regression analyses were conducted. First, an
      analysis was conducted comparing the odds of having a short-term disability claim
      between patients with and without migraine after controlling for patient
      demographic and clinical characteristics. A second analysis, conducted among the
      migraine patients only, compared the odds of having a short-term disability claim
      between (1) patients treated with acute or preventive migraine medications only
      during the baseline period and patients with no migraine treatment during
      baseline and (2) patients treated with both acute and preventive migraine
      medications during the baseline period and patients with no migraine treatment
      during baseline, after controlling for patient demographic and clinical
      characteristics. RESULTS: Migraine patients had total annual direct plus indirect
      costs that were $8924 (in 2014 United States dollars) higher than those of
      demographically similar individuals without evidence of migraine. Migraine
      patients' mean annual direct all-cause healthcare costs were $6575 higher than
      those of matched patients without migraine ($11,010 [standard deviation =
      $19,663] vs $4436 [standard deviation=$13,081]; P < .01). Total mean annual
      indirect costs were $2350 higher in the migraine cohort than in the matched no
      migraine patients ($11,294 vs $8945. Migraine patients were 2.0 times more likely
      as their nonmigraine counterparts to use opioids (45.5% vs 21.9%; P < .01) and
      among patients with opioid prescriptions, migraine patients had 1.8 times the
      number of opioid prescriptions per patient than did those without migraine (4.9
      [standard deviation = 6.9] vs 2.7 [standard deviation = 4.0]; P < .01). After
      adjusting for baseline demographic and clinical characteristics, migraine
      patients treated with either acute or preventive migraine medications (odds ratio
      = 0.81 [95% confidence interval = 0.72-0.91]; P < .01) or both acute and
      preventive migraine medications during the baseline period (odds ratio = 0.93
      [95% confidence interval = 0.89-0.98]; P < .01) were significantly less likely to
      have short-term disability claims than untreated patients during the follow-up
      period (Migraine patients with either acute or preventive medications only:
      7290/45,632 [16.0%]; with both acute and preventive medications: 3085/14,941
      [20.6%]; untreated patients: 1604/11,169 [14.4%] had a short-term disability
      claim.) However, overall, migraine patients had 1.94 times the odds of having a
      short-term disability claim than their matched counterparts (95% confidence
      interval = 1.83-2.05; P < .01; migraine patients: 11,979/71,742 [16.7%];
      nonmigraine patients: 4801/71,742 [6.7%] had a short-term disability claim).
      CONCLUSIONS: Results from this real-world assessment of the economic burden of
      migraine suggest that migraine imposes a substantial direct and indirect cost
      burden in the United States. Compared to matched nonmigraine patients, migraine
      patients were more likely to have work loss and longer periods of work loss,
      leading to significantly higher indirect costs. Migraine patients also had higher
      levels of healthcare utilization, despite the relatively stable prevalence of
      migraine and the available acute and preventive treatment options for migraine
      management.

PMID- 29446064
TI  - Roles of community pharmacists in improving oral health awareness in Plateau
      State, Northern Nigeria.
AB  - INTRODUCTION: There is poor oral health awareness in Nigeria because of limited
      access to correct information on oral health as well as a lack of oral health
      care providers. The purpose of this study was to describe the roles of community
      pharmacists (CPs) in Plateau State, Northern Nigeria, as sources of oral health
      information in their communities. METHODS: A quantitative cross-sectional study
      on CPs spanning the entire State. Data collection was a survey method using a
      structured paper-based self-administered questionnaire. Analysis, which included
      t-tests and binary logistic regression, was carried out using SPSS ver. 23.
      RESULTS: A one-sample t-test to assess the attitudes of CPs on oral health showed
      that they had a very good disposition towards engaging in oral health services
      [advice, referrals, recommendations and basic treatment (e.g. of pain); mean  =
      4.54, standard deviation  = 0.59, t(111) = 27.8, P < 0.001]. Although CPs
      presently provide some services to patients with oral health problems, 94.7% were
      willing to do more to advance the cause of oral health care. Training of CPs on
      oral health (32%), removal of restrictive policies in the health bill (1.8%) and
      sensitising the public (6.3%) were some suggestions on how to improve these
      services. CONCLUSION: The disposition of CPs towards improving oral health could
      serve as a platform to help propagate oral health care and awareness in their
      communities. Engaging the CPs might help to reduce oral health disparities by
      increasing oral health awareness and improving the quality of life via cost
      effective delivery of pharmacy-based oral health-care services.

PMID- 29446065
TI  - Simulating Variation in Families' Spending across Marketplace Plans.
AB  - OBJECTIVE: To examine variations in premium and cost-sharing across marketplace
      plans available to eligible families. DATA SOURCES: 2011-2012 Medical Expenditure
      Panel Survey (MEPS), 2014 health plan data from healthcare.gov, and the 2011
      Medicare Part D public formulary file. STUDY DESIGN: We identified a nationally
      representative cohort of individuals in the MEPS who would have been eligible for
      marketplace coverage. For each family, we simulated the total out-of-pocket
      payment (premium plus cost-sharing) under each available plan in their county of
      residence, assuming their premarketplace use. DATA COLLECTION/EXTRACTION METHODS:
      Confidential state and county of residence identifiers were merged onto MEPS
      public use files and used to match MEPS families to the plans available in their
      county as reported in the publicly available data from healthcare.gov. PRINCIPAL
      FINDINGS: We found substantial variation in total family health care spending,
      especially premium component, across marketplace plans. This is true even within
      a plan tier of the same minimum actuarial value, and for families eligible for
      subsidies. Variation among families with income below 250 percent of the FPL is
      larger than variation among families with higher income. CONCLUSIONS: Our
      simulations show substantial variations in net premium and out-of-pocket payments
      across marketplace plans, even within a plan tier.

PMID- 29446066
TI  - Resource Use During the Last 6 Months of Life of Individuals Dying with and of
      Alzheimer's Disease.
AB  - OBJECTIVES: To compare resource use during the last 6 months of life of
      individuals diagnosed with Alzheimer's disease (AD) but for whom AD was not
      formally identified as the underlying cause of death (dying with AD) with that of
      those who had AD as underlying cause of death (dying of AD). DESIGN: Full
      population retrospective analysis. SETTING: Belgium. PARTICIPANTS: All Belgian
      decedents in 2012. MEASUREMENTS: We linked participants' healthcare, population,
      and death certificate data. Those who died of AD were selected based on
      underlying cause of death. Those who died with AD were selected using a validated
      algorithm. RESULTS: Individuals who died of AD had less hospital use than those
      who died with AD; were less often admitted to a palliative care unit but received
      palliative home care services slightly more often; and had use of physiotherapy,
      noninvasive ventilation, medical imaging, sedatives, oxygen, and opioids
      comparable with that of those who died with AD. CONCLUSION: During the last 6
      months of life, individuals dying of AD used fewer intensive resources such as
      intensive care unit, cardiopulmonary resuscitation, and invasive ventilation than
      those dying with AD, which suggests the effect of recognition of an end-of-life
      phase. Overall, individuals with AD rarely used palliative care services,
      suggesting a need for more efforts to encourage use of palliative care in
      individuals with AD.

PMID- 29446067
TI  - Headache Linked to Intracranial Hypertension and Hypertrophic Pachymeningitis as
      the Initial and Dominant Presentation of Granulomatosis With Polyangiitis. Case
      Report and Review of the Recent Literature.
AB  - OBJECTIVE: The objective of this article is to report a rare case of headache as
      the initial symptom of granulomatosis with polyangiitis (GPA) and to review the
      recent literature. BACKGROUND: Granulomatosis with polyangiitis is a rare,
      systemic, autoimmune disease of unknown etiology. GPA has a wide spectrum of
      clinical symptomatology, including involvement of the nervous system, even as the
      initial manifestation. Symptoms of the peripheral nervous system used to dominate
      the clinical symptomatology. However, recent reports are focusing increasingly in
      granulomatous lesions of the central nervous system, and especially on the
      increased frequency of patients with hypertrophic pachymeningitis (HP). We report
      the case of a patient with headache linked to intracranial hypertension and
      hypertrophic pachymeningitis as the initial and dominant presentation of GPA and
      we review the recent literature. METHODS: A 54-year-old male, without any related
      medical history developed a severe headache. In the following 2 months, he
      gradually developed hoarseness and diplopia at the left and lower fields of
      vision. A brain MRI revealed wide-spread fattening and meningeal enhancement over
      the left hemisphere and the left cerebellar hemisphere. An endoscopy of the
      pharynx revealed the presence of a tumor-like mass in the left half of the
      nasopharynx. A biopsy showed inflammation with presence of polykaryocyte Langhans
      giant cells. The laboratory testing revealed important albuminuria and
      microhematuria, positive c-ANCA and negative p-ANCA. A diagnosis of GPA was
      established. RESULTS: A steroid treatment was administered initially, which
      improved the headache drastically, followed by the administration of a
      combination of cyclophosphamide and corticosteroid, which led to a gradual
      resolve of the remaining symptomatology. A follow-up brain MRI showed a decrease
      in meningeal enhancement, whereas a second one, 2 years later, was completely
      normal. CONCLUSIONS: HP was considered an extremely rare manifestation of GPA.
      However, recent studies are reporting an increased frequency of HP and are
      distinguishing a granulomatous and a vasculitic phenotype, with different
      localization and relapse rates, that may eventually constitute a different
      clinical spectrum of GPA.

PMID- 29446068
TI  - Model-Informed Drug Development for Ixazomib, an Oral Proteasome Inhibitor.
AB  - Model-informed drug development (MIDD) was central to the development of the oral
      proteasome inhibitor ixazomib, facilitating internal decisions (switch from body
      surface area (BSA)-based to fixed dosing, inclusive phase III trials, portfolio
      prioritization of ixazomib-based combinations, phase III dose for maintenance
      treatment), regulatory review (model-informed QT analysis, benefit-risk of 4 mg
      dose), and product labeling (absolute bioavailability and intrinsic/extrinsic
      factors). This review discusses the impact of MIDD in enabling patient-centric
      therapeutic optimization during the development of ixazomib.

PMID- 29446069
TI  - Accelerated Development of the Dual Orexin Receptor Antagonist ACT-541468:
      Integration of a Microtracer in a First-in-Human Study.
AB  - The orexin system regulates sleep and arousal and is targeted by ACT-541468, a
      new dual orexin receptor antagonist (DORA). Healthy male subjects received a
      single oral dose of 5-200 mg to assess safety, tolerability, pharmacokinetics
      (PK), pharmacodynamics (PD), mass balance, metabolism, and absolute
      bioavailability utilizing a 14 C-labeled, orally and intravenously (i.v.)
      administered microtracer. The drug was safe and well tolerated; the PK profile
      was characterized by quick absorption and elimination, with median time to reach
      maximum concentration (tmax ) of 0.8-2.8 h and geometric mean terminal half-life
      (t1/2 ) of 5.9-8.8 h. Clear dose-related effects on the central nervous system
      were observed at >=25 mg, indicating a suitable PK-PD profile for a sleep
      promoting drug, allowing for rapid onset and duration of action limited to the
      intended use. This comprehensive first-in-human study created a wealth of data,
      while saving resources in drug development.

PMID- 29446070
TI  - A Hospital Based Retrospective Study of Acute Postpartum Headache.
AB  - OBJECTIVE: To describe acute headache diagnoses in women presenting emergently in
      the postpartum period and to determine which factors may be associated with
      secondary vs primary headache. BACKGROUND: Hormonal, vascular, and procedural
      factors elevate the risk for both secondary and primary headache disorders in the
      postpartum period. Differentiating between these can be a diagnostic challenge,
      particularly among the most severe patients referred for urgent neurological
      consultation. METHODS: A single-center retrospective study of consecutive
      postpartum women age >=18 years presenting with acute headache to a large urban
      tertiary-care hospital and receiving neurological consultation. RESULTS: Of 63
      women who presented with acute postpartum headache, 17 (27.0%) were diagnosed
      with a primary headache disorder and 46 (73.0%) were diagnosed with a secondary
      headache disorder. Migraine comprised the majority of primary headache diagnoses
      (76.5%). Secondary headache most commonly featured postdural puncture headache
      (PDPH) (45.7%), postpartum preeclampsia (PEC) (26.1%), and a diverse group of
      cerebrovascular headache disorders (21.7%). Presentation within 24 hours and lack
      of side predominance helped to differentiate PDPH from migraine. However,
      abnormal diagnostic testing was more prevalent in the patients with headache
      secondary to cerebrovascular disorders/PEC. CONCLUSIONS: Nearly three-quarters of
      postpartum women who present with acute onset headache and receiving neurological
      consultation are found to have a secondary headache - with nearly half of the
      secondary headaches attributed to PEC or cerebrovascular headache disorders. The
      absence of a headache history and a clear PDPH description should prompt strong
      consideration for neuroimaging to rule out cerebrovascular etiologies of headache
      as well as close monitoring for signs and symptoms of preeclampsia in women
      presenting with acute severe postpartum headache.

PMID- 29446071
TI  - Indistinguishability tests in the actor-partner interdependence model.
AB  - When considering dyadic data, one of the questions is whether the roles of the
      two dyad members can be considered equal. This question may be answered
      empirically using indistinguishability tests in the actor-partner interdependence
      model. In this paper several issues related to such indistinguishability tests
      are discussed: the difference between maximum likelihood and restricted maximum
      likelihood based tests for equality in variance parameters; the choice between
      the structural equation modelling and multilevel modelling framework; and the use
      of sequential testing rather than one global test for a set of
      indistinguishability tests. Based on simulation studies, we provide guidelines
      for best practice. All different types of tests are illustrated with cross
      sectional and longitudinal data, and corroborated with corresponding R code.

PMID- 29446072
TI  - Sleep in a comparative context: Investigating how human sleep differs from sleep
      in other primates.
AB  - OBJECTIVES: Primates vary in their sleep durations and, remarkably, humans sleep
      the least per 24-hr period of the 30 primates that have been studied. Using
      phylogenetic methods that quantitatively situate human phenotypes within a
      broader primate comparative context, we investigated the evolution of human sleep
      architecture, focusing on: total sleep duration, rapid eye movement (REM) sleep
      duration, non-rapid eye movement (NREM) sleep duration, and proportion of sleep
      in REM. MATERIALS AND METHODS: We used two different Bayesian methods:
      phylogenetic prediction based on phylogenetic generalized least squares and a
      multistate Onrstein-Uhlenbeck (OU) evolutionary model of random drift and
      stabilizing selection. RESULTS: Phylogenetic prediction confirmed that humans
      sleep less than predicted for a primate of our body mass, predation risk, brain
      size, foraging needs, sexual selection, and diet. These analyses further revealed
      that humans pack an unexpectedly higher proportion of REM sleep within a shorter
      overall sleep duration, and do so by reducing NREM sleep (rather than increasing
      REM). The OU model generally confirmed these findings, with shifts along the
      human lineage inferred for TST, NREM, and proportion of REM, but not for REM.
      DISCUSSION: We propose that the risks and opportunity costs of sleep are
      responsible for shorter sleep durations in humans, with risks arising from
      terrestrial sleep involving threats from predators and conspecifics, and
      opportunity costs because time spent sleeping could be used for learning,
      creating material objects, and socializing.

PMID- 29446073
TI  - CCR2-dependent Gr1high monocytes promote kidney injury in shiga toxin-induced
      hemolytic uremic syndrome in mice.
AB  - The hemolytic uremic syndrome (HUS) is a life-threatening disease of the kidney
      that is induced by shiga toxin-producing E.coli. Major changes in the monocytic
      compartment and in CCR2-binding chemokines have been observed. However, the
      specific contribution of CCR2-dependent Gr1high monocytes is unknown. To
      investigate the impact of these monocytes during HUS, we injected a combination
      of LPS and shiga toxin into mice. We observed an impaired kidney function and
      elevated levels of the CCR2-binding chemokine CCL2 after shiga toxin/LPS-
      injection, thus suggesting Gr1high monocyte infiltration into the kidney. Indeed,
      the number of Gr1high monocytes was strongly increased one day after HUS
      induction. Moreover, these cells expressed high levels of CD11b suggesting
      activation after tissue entry. Non-invasive PET-MR imaging revealed kidney injury
      mainly in the kidney cortex and this damage coincided with the detection of
      Gr1high monocytes. Lack of Gr1high monocytes in Ccr2-deficient animals reduced
      neutrophil gelatinase-associated lipocalin and blood urea nitrogen levels.
      Moreover, the survival of Ccr2-deficient animals was significantly improved.
      Conclusively, this study demonstrates that CCR2-dependent Gr1high monocytes
      contribute to the kidney injury during HUS and targeting these cells is
      beneficial during this disease.

PMID- 29446075
TI  - Surface smoothing, decimation, and their effects on 3D biological specimens.
AB  - OBJECTIVE: Smoothing and decimation filters are commonly used to restore the
      realistic appearance of virtual biological specimens, but they can cause a loss
      of topological information of unknown extent. In this study, we analyzed the
      effect of smoothing and decimation on a 3D mesh to highlight the consequences of
      an inappropriate use of these filters. MATERIALS AND METHODS: Topological noise
      was simulated on four anatomical regions of the virtual reconstruction of an
      orangutan cranium. Sequential levels of smoothing and decimation were applied,
      and their effects were analyzed on the overall topology of the 3D mesh and on
      linear and volumetric measurements. RESULTS: Different smoothing algorithms
      affected mesh topology and measurements differently, although the influence on
      the latter was generally low. Decimation always produced detrimental effects on
      both topology and measurements. The application of smoothing and decimation, both
      separate and combined, is capable of recovering topological information.
      CONCLUSION: Based on the results, objective guidelines are provided to minimize
      information loss when using smoothing and decimation on 3D meshes.

PMID- 29446076
TI  - Topical application of glycyrrhetinic acid in the gingival sulcus inhibits
      attachment loss in lipopolysaccharide-induced experimental periodontitis in rats.
AB  - BACKGROUND AND OBJECTIVE: Attachment loss of the junctional epithelium and
      alveolar bone destruction are signs of periodontitis, which is mainly caused by
      an inflammatory response to dental plaque. Glycyrrhetinic acid (GA), a component
      of the licorice herb, has been shown to have important anti-inflammatory
      activities; however, there are no previous reports on the ability of its
      inhibitory effects to prevent periodontal diseases. Hence, in this study, using
      our experimental periodontitis model, we attempted to evaluate whether GA had an
      effect on the prevention of attachment loss and alveolar bone loss. MATERIAL AND
      METHODS: Rats were intraperitoneally immunized with Escherichia coli
      lipopolysaccharide (LPS). The LPS group (n = 5) received 3 topical applications
      of 50 MUg/MUL of LPS followed by one application of the vehicle (propylene
      glycol:ethyl alcohol:phosphate-buffered saline [PBS] = 8:1:1) into the gingival
      sulcus. This protocol was repeated twice per day for 10 days. The low (n = 5) and
      high (n = 5) groups received topical application of LPS and 0.03% or 0.3% GA,
      respectively. The control group received topical application of PBS and vehicle.
      The rats were killed on the 10th day. Attachment loss, alveolar bone level and
      inflammatory cell infiltration were investigated histometrically. The formation
      of immune complexes and infiltration of LPS were evaluated immunohistologically.
      RESULTS: Attachment loss, formation of immune complexes and infiltration of
      inflammatory cells were increased in the LPS group compared with the control
      group, and were completely inhibited in the low and high groups compared with the
      LPS group. The LPS group showed greater alveolar bone destruction compared with
      the control group and GA-treated groups. In addition, invasion of LPS was
      detected in the LPS group, was absent in the control group and was weaker in the
      GA-treated groups than in the LPS group. CONCLUSION: In the present study, we
      showed that GA inhibits periodontal destruction in the rat experimental
      periodontitis model.

PMID- 29446074
TI  - A Hitchhiker's guide to humanized mice: new pathways to studying viral
      infections.
AB  - Humanized mice are increasingly appreciated as an incredibly powerful platform
      for infectious disease research. The often very narrow species tropism of many
      viral infections, coupled with the sometimes misleading results from preclinical
      studies in animal models further emphasize the need for more predictive model
      systems based on human cells rather than surrogates. Humanized mice represent
      such a model and have been greatly enhanced with regards to their immune system
      reconstitution as well as immune functionality in the past years, resulting in
      their recommendation as a preclinical model by the US Food and Drug
      Administration. This review aims to give a detailed summary of the generation of
      human peripheral blood lymphocyte-, CD34+ haematopoietic stem cell- and bone
      marrow/liver/thymus-reconstituted mice and available improved models (e.g.
      myeloid- or T-cell-only mice, MISTRG, NSG-SGM3). Additionally, we summarize human
      tropic viral infections, for which humanized mice offer a novel approach for the
      study of disease pathogenesis as well as future perspectives for their use in
      biomedical, drug and vaccine research.

PMID- 29446077
TI  - Coffee drinking and colorectal cancer and its subsites: A pooled analysis of 8
      cohort studies in Japan.
AB  - Coffee is a rich source of bioactive compounds that have potential
      anticarcinogenic effects. However, it remains unclear whether coffee drinking is
      associated with colorectal cancer. Also, despite different etiological factors
      involved in gut physiology, few studies have investigated this association by
      anatomical site of the lesion. To address these issues, this study examined the
      association between coffee drinking and colorectal cancer in a pooled analysis
      from 8 cohort studies conducted in Japan. Among 320,322 participants followed up
      for 4,503,274 person-years, 6,711 incident colorectal cancer cases were
      identified. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs)
      were estimated using Cox proportional hazards models and then pooled using the
      random effects model. Coffee drinking was not materially associated with
      colorectal cancer risk in men or women (pooled HR 0.92, 95% CI 0.82-1.03 in men
      and pooled HR 0.90, 95% CI 0.76-1.07 in women). Analysis by subsite showed a
      lower risk of colon cancer among female drinkers of >=3 cups coffee/day (pooled
      HR 0.80, 95% CI 0.64-0.99). There was no such association in men. Coffee drinking
      was not associated with risk of rectal cancer in men or women. Results were
      virtually the same among never smokers except for an increased risk of rectal
      cancer associated with frequent coffee consumption. Coffee drinking may be
      associated with lower risk of colon cancer in Japanese women.

PMID- 29446079
TI  - Dietary intake of nutrients involved in one-carbon metabolism and risk of
      urothelial cell carcinoma: A prospective cohort study.
AB  - Nutrients involved in one-carbon metabolism may play a role in carcinogenesis
      through DNA replication, repair and methylation mechanisms. Most studies on
      urothelial cell carcinoma (UCC) have focused on folate. We sought to examine the
      association between B-group vitamins and methionine intake and UCC risk, overall
      and by subtype, and to test whether these associations are different for
      population subgroups whose nutritional status may be compromised. We followed
      participants in the Melbourne Collaborative Cohort Study (N = 41,513) for over 20
      years and observed 500 UCC cases (89% originating in the bladder; superficial:
      279, invasive: 221). Energy-adjusted dietary intakes of B vitamins (B1, B2, B3,
      B5, B6, B8, B9 and B12) and methionine were estimated from a 121-item food
      frequency questionnaire administered at baseline (1990-1994), using the residuals
      method. We used Cox regression models to compute hazard ratios (HRs) of UCC risk
      per standard deviation (SD) of log-transformed nutrient intakes and 95%
      confidence intervals, adjusted for potential confounders. We investigated
      associations by tumor subtype, and tested interactions with sex, country of
      birth, smoking and alcohol drinking. The risk of UCC appeared not to be
      associated with intake of B-group vitamins or methionine, and findings were
      consistent across tumor subtypes and across demographic and lifestyle
      characteristics of the participants. A potential interaction between vitamin B1
      and alcohol drinking was observed (all participants: HR per 1 SD = 0.99 (0.91
      1.09), never drinkers: HR = 0.81 (0.69-0.97), p-interaction = 0.02), which needs
      to be confirmed by other studies. Our findings do not indicate that dietary
      intake of nutrients involved in one-carbon metabolism are associated with UCC
      risk.

PMID- 29446078
TI  - A real-time method to simultaneously measure linear energy transfer and dose for
      proton therapy using organic scintillators.
AB  - PURPOSE: Currently, no detectors are capable of simultaneously measuring dose and
      linear energy transfer (LET) in real time. In this study, we evaluated the
      feasibility of exploiting the difference in the response of various organic
      plastic scintillation detectors to measure LET and dose in therapeutic proton
      beams. The hypothesis behind this work was that the ratio of the responses of
      different scintillators exposed to the same proton beam can be used to obtain a
      LET vs ratio calibration curve that can then be used to infer LET under any other
      measurement conditions. METHODS: We first used similar scintillators with
      different ionization quenching factors. LET values for different irradiation
      conditions were calculated using a validated Monte Carlo model of the proton beam
      line. The quenching factors in the Birks equation for different scintillators as
      a function of LET were obtained from measurements in a 100-MeV pristine proton
      beam. We then used four different organic scintillation materials - polystyrene
      (BCF-12), poly (methyl methacrylate), polyvinyltoluene, and a liquid scintillator
      - for which the LET response varied with regard to not only quenching but also
      differences in material density and relative stopping power. We simultaneously
      exposed the four different organic scintillators and a plane-parallel ion chamber
      to passively scattered proton beams at fluence-averaged LET. Comparisons to the
      expected values obtained from the Monte Carlo simulations were made on the basis
      of both dose and LET. RESULTS: The maximum difference in the quenching factor was
      20%, resulting in a 5% change in LET with a response ratio over a range of 5
      keV/MUm. Among all the scintillators investigated, the ratio of PMMA to BCF-12
      provided the best correlation with LET values and was therefore used to construct
      the LET calibration curve. The expected LET values in the validation set were
      within 2% +/- 6%, which resulted in dose accuracy of 1.5% +/- 5.8% for the range
      of LET values investigated in this work. CONCLUSIONS: We demonstrated the
      feasibility of using the ratio of the light outputs of two organic scintillators
      to simultaneously measure LET and dose in therapeutic proton beams for fluence
      averaged LET values from 0.47 to 1.26 keV/MUm. Further studies are needed to
      verify the response for higher LET values and the reproducibility of this method.

PMID- 29446080
TI  - Allegro giusto: piccolo, bassoon and clarinet set the tempo of vesicle pool
      replenishment.

PMID- 29446081
TI  - Under the weather?-The direct effects of climate warming on a threatened desert
      lizard are mediated by their activity phase and burrow system.
AB  - For ectotherms such as lizards, the importance of behavioural thermoregulation in
      avoiding thermal extremes is well-established and is increasingly acknowledged in
      modern studies of climate warming and its impacts. Less appreciated and
      understood are the buffering roles of retreat sites and activity phase, in part
      because of logistical challenges of studying below-ground activity. Burrowing and
      nocturnal activity are key behavioural adaptations that have enabled a diverse
      range of reptiles to survive extreme environmental temperatures within hot desert
      regions. Yet, the direct impact of recent global warming on activity potential
      has been hypothesised to have caused extinctions in desert lizards, including the
      Australian arid zone skink Liopholis kintorei. We test the relevance of this
      hypothesis through a detailed characterisation of the above- and below-ground
      thermal and hydric microclimates available to, and used by, L. kintorei. We
      integrate operative temperatures with observed body temperatures to construct
      daily activity budgets, including the inference of subterranean behaviour. We
      then assess the likelihood that contemporary and future local extinctions in this
      species, and those of similar burrowing habits, could be explained by the direct
      effects of warming on its activity budget and exposure to thermal extremes. We
      found that L. kintorei spent only 4% of its time active on the surface, primarily
      at dusk, and that overall potential surface activity will be increased, not
      restricted, with climate warming. The burrow system provides an exceptional
      buffer to current and future maximum extremes of temperature (~40 degrees C
      reduction from potential surface temperatures), and desiccation (burrows near
      100% humidity). Therefore, any climate warming impacts on this species are likely
      to be indirect. Our findings reflect the general buffering capacity of
      underground microclimates, therefore, our conclusions for L. kintorei are more
      generally applicable to nocturnal and crepuscular ectotherms, and highlight the
      need to consider the buffering properties of retreat sites and activity phase
      when forecasting climate change impacts.

PMID- 29446082
TI  - Development of a dual-energy computed tomography quality control program:
      Characterization of scanner response and definition of relevant parameters for a
      fast-kVp switching dual-energy computed tomography system.
AB  - PURPOSE: A prototype QC phantom system and analysis process were developed to
      characterize the spectral capabilities of a fast kV-switching dual-energy
      computed tomography (DECT) scanner. This work addresses the current lack of
      quantitative oversight for this technology, with the goal of identifying relevant
      scan parameters and test metrics instrumental to the development of a dual-energy
      quality control (DEQC). METHODS: A prototype elliptical phantom (effective
      diameter: 35 cm) was designed with multiple material inserts for DECT imaging.
      Inserts included tissue equivalent and material rods (including iodine and
      calcium at varying concentrations). The phantom was scanned on a fast kV
      switching DECT system using 16 dual-energy acquisitions (CTDIvol range: 10.3-62
      mGy) with varying pitch, rotation time, and tube current. The circular head
      phantom (22 cm diameter) was scanned using a similar protocol (12 acquisitions;
      CTDIvol range: 36.7-132.6 mGy). All acquisitions were reconstructed at 50, 70,
      110, and 140 keV and using a water-iodine material basis pair. The images were
      evaluated for iodine quantification accuracy, stability of monoenergetic
      reconstruction CT number, noise, and positional constancy. Variance component
      analysis was used to identify technique parameters that drove deviations in test
      metrics. Variances were compared to thresholds derived from manufacturer
      tolerances to determine technique parameters that had a nominally significant
      effect on test metrics. RESULTS: Iodine quantification error was largely
      unaffected by any of the technique parameters investigated. Monoenergetic HU
      stability was found to be affected by mAs, with a threshold under which spectral
      separation was unsuccessful, diminishing the utility of DECT imaging. Noise was
      found to be affected by CTDIvol in the DEQC body phantom, and CTDIvol and mA in
      the DEQC head phantom. Positional constancy was found to be affected by mAs in
      the DEQC body phantom and mA in the DEQC head phantom. CONCLUSION: A streamlined
      scan protocol was developed to further investigate the effects of CTDIvol and
      rotation time while limiting data collection to the DEQC body phantom. Further
      data collection will be pursued to determine baseline values and statistically
      based failure thresholds for the validation of long-term DECT scanner
      performance.

PMID- 29446083
TI  - Development and clinical characterization of a novel 2041 liquid-filled
      ionization chambers array for high-resolution verification of radiotherapy
      treatments.
AB  - PURPOSE: The aim of this study was to present a novel 2041 liquid-filled
      ionization chamber array for high-resolution verification of radiotherapy
      treatments. MATERIALS AND METHODS: The prototype has 2041 ionization chambers of
      2.5 * 2.5 mm2 area filled with isooctane. The detection elements are arranged in
      a central square grid of 43 * 43, totally covering an area of 107.5 * 107.5 mm2 .
      The central inline and cross-line are extended to 227 mm and the diagonals to 321
      mm to be able to perform profile measurements of large fields. We have studied
      stability, pixel response uniformity, dose rate dependence, depth and field size
      dependence and anisotropy. We present results for output factors, tongue-and
      groove, garden fence, small field profiles, irregular fields, and verification of
      dose planes of patient treatments. RESULTS: Comparison with other detectors used
      for small field dosimetry (SFD, CC13, microDiamond) has shown good agreement.
      Output factors measured with the device for square fields ranging from 10 * 10 to
      100 * 100 mm2 showed relative differences within 1%. The response of the detector
      shows a strong dependence on the angle of incident radiation that needs to be
      corrected for. On the other hand, inter-pixel relative response variations in the
      0.95-1.08 range have been found and corrected for. The application of the device
      for the verification of dose planes of several treatments has shown gamma passing
      rates above 97% for tolerances of 2% and 2 mm. The verification of other clinical
      fields, like small fields and irregular fields used in the commissioning of the
      TPS, also showed large passing rates. The verification of garden fence and tongue
      and-groove fields was affected by volume-averaging effects. CONCLUSIONS: The
      results show that the liquid filled ionization chamber prototype here presented
      is appropriate for the verification of radiotherapy treatments with high spatial
      resolution. Recombination effects do not affect very much the verification of
      relative dose distributions. However, verification of absolute dose distributions
      may require normalization to a radiation field which is representative of the
      dose rate of the treatment delivered.

PMID- 29446084
TI  - An assessment of injection site reaction and injection site pain of 1-month and 3
      month long-acting injectable formulations of paliperidone palmitate.
AB  - PURPOSE: To evaluate injection site reactions and pain following paliperidone
      palmitate 1-month (PP1M) and 3-month (PP3M) administration using safety data of
      double-blind (DB), noninferiority study. METHODS: Patients (n = 1,429) with
      schizophrenia, treated with PP1M (50-150 mg-eq, 17-week open-label [OL] phase)
      were randomized to PP1M or PP3M in 48-week DB phase. FINDINGS: PP1M and PP3M
      injections were well tolerated. Incidence of induration, redness, and swelling
      were low in both phases (OL: 9-12%; DB: 7-13%), and were mostly mild in both
      groups. Mean (SD) visual analog scale scores decreased from OL-baseline (22.0
      [21.6]) to DB-baseline (19.5 [20.6] vs. 18.4 [20.4]) and DB-endpoint (15.6 [17.9]
      vs. 15.5 [18.3]). PRACTICE IMPLICATIONS: Injection site reactions and pain were
      low and similar between both treatments, regardless of administration site and
      dose.

PMID- 29446085
TI  - DR4 mediates the progression, invasion, metastasis and survival of colorectal
      cancer through the Sp1/NF1 switch axis on genomic locus.
AB  - The single nucleotide polymorphism (SNP), -397G > T (rs13278062) polymorphism, in
      the promoter of Death Receptor 4 (DR4) had been reported to be associated with a
      significantly increased risk for bladder cancer. However, the association of this
      SNP with the risk of colorectal cancer has not been reported. In this study, we
      performed a case-control study in 1,078 colorectal cancer patients and 1,175
      matched healthy controls to evaluate the association of the potential functional
      genetic variants in DR4 with risk and survival of colorectal cancer. PCR-TaqMan
      were used to genotype the rs13278062, rs1000294 and rs2235126 polymorphisms. We
      found that subjects carrying the rs13278062 GT/TT genotypes had a significantly
      lower risk and increased survival time when compared to the GG genotype. We also
      constructed the rs13278062 GT/TT genotype in SW480 and SW620 cells (rs13278062 is
      GG in both cell lines) with the CRISPR/Cas9 system. Flow cytometry experiments
      showed that the rs13278062 TT genotype promoted apoptosis in colorectal cancer
      cells. In vitro and in vivo experiments established that the rs13278062 G to T
      mutation inhibited carcinogenesis and metastasis of colorectal cancer. Chromatin
      immunoprecipitation (ChIP) assays revealed that the rs13278062 G > T polymorphism
      altered the binding affinity of the transcription factors Sp1/NF1 to the
      rs13278062 mutation region. Immunohistochemistry, western blot, and qPCR
      corroborated that the rs13278062 GT/TT genotypes increased the expression of DR4
      protein in colorectal cancer tissues and cells. In conclusion, these findings
      indicate that DR4 mediated progression, invasion, metastasis and survival of
      colorectal cancer via the Sp1/NF1 switch axis on genomics locus.

PMID- 29446086
TI  - Subchondral bone morphology in the metacarpus of racehorses in training changes
      with distance from the articular surface but not with age.
AB  - The repetitive large loads generated during high-speed training and racing
      commonly cause subchondral bone injuries in the metacarpal condyles of
      racehorses. Adaptive bone modelling leads to focal sclerosis at the site of
      highest loading in the palmar aspect of the metacarpal condyles. Information on
      whether and how adaptive modelling of subchondral bone changes during the career
      of a racehorse is sparse. The aim of this cross-sectional study was to describe
      the changes in subchondral bone micromorphology in the area of highest loading in
      the palmar aspect of the metacarpal condyle in thoroughbred racehorses as a
      function of age and training. Bone morphology parameters derived from micro-CT
      images were evaluated using principal component analysis and mixed-effects linear
      regression models. The largest differences in micromorphology were observed in
      untrained horses between the age of 16 and 20 months. Age and duration of a
      training period had no influence on tissue mineral density, bone volume fraction
      or number and area of closed pores to a depth of 5.1 mm from the articular
      surface in 2- to 4-year-old racehorses in training. Horses with subchondral bone
      injuries had more pores in cross-section compared with horses without subchondral
      bone injuries. Differences in bone volume fraction were due to the volume of less
      mineralised bone. Tissue mineral density increased and bone volume fraction
      decreased with increasing distance from the articular surface up to 5.1 mm from
      the articular surface. Further research is required to elucidate the
      biomechanical and pathophysiological consequences of these gradients of
      micromorphological parameters in the subchondral bone.

PMID- 29446087
TI  - Open Access: Is There a Predator at the Door?

PMID- 29446089
TI  - Morphometric and histopathological evaluation of the effect of grape seed
      proanthocyanidin on alveolar bone loss in experimental diabetes and
      periodontitis.
AB  - OBJECTIVE: Grape seed proanthocyanidine extract (GSPE) is a strong antioxidant
      derived from the grape seeds (Vitis vinifera, Terral J.F.) and has a polyphenolic
      structure with a wide range of biological activity. The aim of the present study
      was to evaluate the effects of GSPE on alveolar bone loss and histopathological
      changes in rats with diabetes mellitus and ligature-induced periodontitis.
      MATERIAL AND METHODS: Forty rats were divided into 6 study groups. Control (C, 6
      rats) group, periodontitis (P, 6 rats) group, diabetes (D, 6 rats) group,
      diabetes and periodontitis (D+P, 6 rats) group, diabetes, periodontitis and 100
      mg/kg/day GSPE (GSPE-100, 8 rats), and diabetes, periodontitis and 200 mg/kg/day
      GSPE (GSPE-200, 8 rats) group. Diabetes mellitus was induced by intraperitoneal
      injection of a single dose of streptozotocin (60 mg/kg). Periodontitis was
      induced via ligation method. Silk ligatures were placed at the mandibular right
      first molars. GSPE was administered by oral gavage. After 30 days, all rats were
      killed. Alveolar bone loss was measured morphometrically via a stereomicroscope.
      For histopathological analyses, Alizarin red staining, and matrix
      metalloproteinase (MMP)-8, vascular endothelial growth factor and hypoxia
      inducible factor (HIF)-1alpha immunohistochemistry were performed. Tartrate
      resistant acid phosphatase-positive osteoclast cells and relative total
      inflammatory cells were also determined. RESULTS: The highest alveolar bone loss
      was observed in the D+P group (P < .05). GSP-200 group decreased alveolar bone
      loss (P < .05). The D+P group had the highest osteoclast counts, but the
      difference was not significant compared to the P, GSPE-100 and GSPE-200 groups (P
      > .05). The inflammation in the D+P group was also higher than the other groups
      (P < .05). The osteoblast numbers increased in the GSPE-100 and GSPE-200 groups
      compared to the P and D+P groups (P < .05). MMP-8 and HIF-1alpha levels were
      highest in the D+P group and GSPE significantly decreased these levels (P < .05).
      CONCLUSION: Within the limits of this animal study, it can be suggested that GSPE
      administration may decrease periodontal inflammation and alveolar bone loss via
      decreasing MMP-8 and HIF-1alpha levels and increase osteoblastic activity in
      diabetic rats with experimental periodontitis.

PMID- 29446090
TI  - Potential lives saved in 73 countries by adopting multi-cohort vaccination of 9
      14-year-old girls against human papillomavirus.
AB  - Up to 2016, low- and middle-income countries mostly introduced routine human
      papillomavirus (HPV) vaccination for just a single age-cohort of girls each year.
      However, high-income countries have reported large reductions in HPV prevalence
      following "catch-up" vaccination of multiple age-cohorts in the year of HPV
      vaccine introduction. We used the mathematical model PRIME to project the
      incremental impact of vaccinating 10- to 14-year-old girls compared to routine
      HPV vaccination only in the same year that routine vaccination is expected to be
      introduced for 9-year-old girls across 73 low- and lower-middle-income countries.
      Adding multiple age-cohort vaccination could increase the number of cervical
      cancer deaths averted by vaccine introductions in 2015-2030 by 30-40% or an
      additional 1.23-1.79 million over the lifetime of the vaccinated cohorts. The
      number of girls needed to vaccinate to prevent one death is 101 in the most
      pessimistic scenario, which is only slightly greater than that for routine
      vaccination of 9-year-old girls (87). These results hold even when assuming that
      girls who have sexually debuted do not benefit from vaccination. Results suggest
      that multiple age-cohort vaccination of 9- to 14-year-old girls could accelerate
      HPV vaccine impact and be cost-effective.

PMID- 29446091
TI  - An evaluation of delay to reinforcement and mand variability during functional
      communication training.
AB  - Children with autism spectrum disorder and other developmental disabilities often
      exhibit invariant responding (i.e., restricted behavioral repertoires), deficits
      in communication, and challenging behavior. Approaches demonstrated in the basic
      and applied literature to increase response variability include extinction, lag
      schedules of reinforcement, and percentile schedules of reinforcement. Results of
      basic studies have also indicated that delays to reinforcement often produce
      increases in response variability. The purpose of the current study was to
      evaluate the effects of a delay to reinforcement on the variability of
      communication responses during functional communication training with individuals
      with developmental disabilities and histories of engaging in challenging
      behavior. Results indicated that delays to reinforcement increased mand
      variability with all four participants with variable effects on challenging
      behavior across participants.

PMID- 29446088
TI  - The Second Visual System of The Tree Shrew.
AB  - This review provides a historical account of the discovery of secondary visual
      pathways (from retina to the superior colliculus to the dorsal thalamus and
      extrastriate cortex), and Vivien Casagrande's pioneering studies of this system
      using the tree shrew as a model. Subsequent studies of visual pathways in the
      tree shrew are also reviewed, beginning with a description of the organization
      and central projections of the tree shrew retina. The organization and
      connectivity of second visual system components that include the retino-recipient
      superior colliculus, tecto-recipient pulvinar nucleus and its projections, and
      the tecto-recipient dorsal lateral geniculate nucleus and its projections are
      detailed. Potential functions of the second visual system are discussed in the
      context of this work and in the context of the behavioral studies that initially
      inspired the secondary visual system concept.

PMID- 29446092
TI  - Association of salivary lactate dehydrogenase level with systemic inflammation in
      a Japanese population.
AB  - BACKGROUND AND OBJECTIVE: Salivary lactate dehydrogenase (LDH) was reported to be
      a useful parameter for the screening of periodontal disease. We performed a cross
      sectional study to verify the usefulness of salivary LDH as a biomarker of
      periodontitis and to investigate the association of severity of periodontitis
      with systemic inflammation by measuring salivary LDH and serum high sensitive C
      reactive protein (hs-CRP) levels in a community-based middle-aged and elderly
      population in Japan. MATERIAL AND METHODS: We recruited 644 men and 1171 women,
      aged 30-79 years, who participated in the Toon Health Study during 2011-15.
      Periodontal condition was assessed by full-mouth examination including mean value
      of probing depth, percentage of probing depth of >=4 mm and >=6 mm, and bleeding
      on probing. Saliva and blood serum samples were collected for measurement of
      salivary LDH level and hs-CRP, respectively. A linear trend across quartiles of
      salivary LDH was calculated using linear regression. Interaction of salivary LDH
      and overweight status (body mass index of >=25 kg/m2 ) was tested using the cross
      product term of log-transformed continuous salivary LDH and overweight status.
      RESULTS: Analysis of covariance adjusted for potential confounders revealed
      strong associations between salivary LDH level and the indicators of periodontal
      condition (P < .01) in both men and women. Sex- and age-adjusted mean values of
      hs-CRP according to salivary LDH quartiles were 0.40, 0.45, 0.45 and 0.50 mg/L (P
      for trend <.01). Although the association was attenuated after further adjustment
      for body mass index, hypertension, diabetes mellitus, dyslipidemia, alcohol
      intake, smoking status and physical activity. When stratified by overweight
      status, the association remained significant in overweight individuals (P = .03).
      The multivariable adjusted odds ratio of hs-CRP level of >=1 mg/L for the highest
      vs lowest quartile of salivary LDH was 1.93 (95% CI, 1.01-3.69) in overweight
      individuals, but not significant in non-overweight individuals. CONCLUSION:
      Salivary LDH appears to be a promising biomarker for the mass screening of
      periodontitis in local community health settings. High salivary LDH levels,
      particularly in overweight individuals might contribute to prevention of
      cardiovascular disease, through measuring systemic inflammatory burdens as well
      as traditional cardiovascular risk factors.

PMID- 29446093
TI  - Effects of neutral and enthusiastic praise on the rate of discrimination
      acquisition.
AB  - Previous research has shown that praise is an effective reinforcer; however, few
      researchers have evaluated whether qualitative differences in praise affect
      responding. The purpose of the current study was to compare the effects of
      neutral, enthusiastic, and no praise on the rate of matching-to-sample
      acquisition during discrete-trial training with adults diagnosed with autism and
      an intellectual disability. In addition, we evaluated preference for neutral,
      enthusiastic, and no praise. All three participants acquired responses slightly
      faster during the enthusiastic praise condition. Preference assessment results
      showed that one participant preferred enthusiastic praise, whereas the two other
      participants showed indiscriminate selections.

PMID- 29446094
TI  - Experimental evidence that density mediates negative frequency-dependent
      selection on aggression.
AB  - Aggression can be beneficial in competitive environments if aggressive
      individuals are more likely to access resources than non-aggressive individuals.
      However, variation in aggressive behaviour persists within populations,
      suggesting that high levels of aggression might not always be favoured. The goal
      of this study was to experimentally assess the effects of population density and
      phenotypic frequency on selection on aggression in a competitive environment. We
      compared survival of two strains of Drosophila melanogaster that differ in
      aggression across three density treatments and five frequency treatments (single
      strain groups, equal numbers of each strain and strains mixed at 3:1 and 1:3
      ratios) during a period of limited resources. While there was no difference in
      survival across single-strain treatments, survival was strongly density
      dependent, with declining survival as density increased. Furthermore, at medium
      and high densities, there was evidence of negative frequency-dependent selection,
      where rare strains experienced greater survival than common strains. However,
      there was no evidence of negative frequency-dependent selection at low density.
      Our results indicate that the benefits of aggression during periods of limited
      resources can depend on the interaction between the phenotypic composition of
      populations and population density, both of which are mechanisms that could
      maintain variation in aggressive behaviours within natural populations.

PMID- 29446095
TI  - Orobanche cernua Loefling Attenuates Ultraviolet B-mediated Photoaging in Human
      Dermal Fibroblasts.
AB  - UV radiation is the primary cause of skin photoaging, which results in an
      increase in matrix metalloproteinases and degradation of collagen. Developing new
      natural antioxidant as photoprotective agents has become a popular area of
      research. Orobanche cernua Loefling is a parasitic plant that is rich in
      phenylethanoid glycosides (PhGs). This study investigated the photoprotective
      effects of the ethanolic extract of Orobanche cernua Loefling (OC) and its
      principal component acteoside on UVB-induced photoaging as well as their
      underlying molecular mechanisms in normal human dermal fibroblasts (NHDFs).
      Biological testing demonstrated that OC and acteoside possessed significant
      photoprotective activities, reducing MMP and IL-6 levels while improving type-I
      procollagen synthesis in UVB-irradiated NHDFs. Further study showed that the
      protective mechanisms were the improvement of transcription factor Nrf2-mediated
      antioxidant defensive system, suppression of MAPK/AP-1 and activation of the TGF
      beta/Smad pathway. Together, our results suggested that OC might be a promising
      antiphotoaging agent against UV radiation-induced skin damage.

PMID- 29446096
TI  - Degradation pattern of a porcine collagen membrane in an in vivo model of guided
      bone regeneration.
AB  - BACKGROUND AND OBJECTIVE: Although collagen membranes have been clinically
      applied for guided tissue/bone regeneration for more than 30 years, their in vivo
      degradation pattern has never been fully clarified. A better understanding of the
      different stages of in vivo degradation of collagen membranes is extremely
      important, considering that the biology of bone regeneration requires the
      presence of a stable and cell/tissue-occlusive barrier during the healing stages
      in order to ensure a predictable result. Therefore, the aim of this study was to
      investigate the degradation pattern of a porcine non-cross-linked collagen
      membrane in an in vivo model of guided bone regeneration (GBR). MATERIAL AND
      METHODS: Decalcified and paraffin-embedded specimens from calvarial defects of
      18, 10-month-old Wistar rats were used. The defects were treated with a double
      layer of collagen membrane and a deproteinized bovine bone mineral particulate
      graft. At 7, 14 and 30 days of healing, qualitative evaluation with scanning
      electron microscopy and atomic force microscopy, and histomorphometric
      measurements were performed. Markers of collagenase activity and bone formation
      were investigated using an immunofluorescence technique. RESULTS: A significant
      reduction of membrane thickness was observed from 7 to 30 days of healing, which
      was associated with progressive loss of collagen alignment, increased collagen
      remodeling and progressive invasion of woven bone inside the membranes. A limited
      inflammatory infiltrate was observed at all time points of healing. CONCLUSION:
      The collagen membrane investigated was biocompatible and able to promote bone
      regeneration. However, pronounced signs of degradation were observed starting
      from day 30. Since successful regeneration is obtained only when cell occlusion
      and space maintenance exist for the healing time needed by the bone progenitor
      cells to repopulate the defect, the suitability of collagen membranes in cases
      where long-lasting barriers are needed needs to be further reviewed.

PMID- 29446097
TI  - Three-dimensional reciprocal space x-ray coherent scattering tomography of two
      dimensional object.
AB  - PURPOSE: X-ray coherent scattering tomography is a powerful tool in
      discriminating biological tissues and bio-compatible materials. Conventional x
      ray scattering tomography framework can only resolve isotropic scattering profile
      under the assumption that the material is amorphous or in powder form, which is
      not true especially for biological samples with orientation-dependent structure.
      Previous tomography schemes based on x-ray coherent scattering failed to preserve
      the scattering pattern from samples with preferred orientations, or required
      elaborated data acquisition scheme, which could limit its application in
      practical settings. Here, we demonstrate a simple imaging modality to preserve
      the anisotropic scattering signal in three-dimensional reciprocal (momentum
      transfer) space of a two-dimensional sample layer. METHODS: By incorporating
      detector movement along the direction of x-ray beam, combined with a tomographic
      data acquisition scheme, we match the five dimensions of the measurements with
      the five dimensions (three in momentum transfer domain, and two in spatial
      domain) of the object. We employed a collimated pencil beam of a table-top copper
      anode x-ray tube, along with a panel detector to investigate the feasibility of
      our method. RESULTS: We have demonstrated x-ray coherent scattering tomographic
      imaging at a spatial resolution ~2 mm and momentum transfer resolution 0.01 A-1
      for the rotation-invariant scattering direction. For any arbitrary, non-rotation
      invariant direction, the same spatial and momentum transfer resolution can be
      achieved based on the spatial information from the rotation-invariant direction.
      The reconstructed scattering profile of each pixel from the experiment is
      consistent with the x-ray diffraction profile of each material. The three
      dimensional scattering pattern recovered from the measurement reveals the
      partially ordered molecular structure of Teflon wrap in our sample. CONCLUSIONS:
      We extend the applicability of conventional x-ray coherent scattering tomography
      to the reconstruction of two-dimensional samples with anisotropic scattering
      profile by introducing additional degree of freedom on the detector. The
      presented method has the potential to achieve low-cost, high-specificity material
      discrimination based on x-ray coherent scattering.

PMID- 29446098
TI  - Safety, efficacy and pharmacokinetics of vedolizumab in patients with
      simultaneous exposure to an anti-tumour necrosis factor.
AB  - BACKGROUND: Data on combination-biologic treatment in (IBD) are still scant. AIM:
      To explore outcomes of patients co-exposed to anti-TNF and vedolizumab. METHODS:
      Patients starting vedolizumab having measurable anti-TNF levels after recently
      stopping adalimumab/infliximab ('VDZ-aTNF' group), were compared with control
      vedolizumab patients in a retrospective 1:2 matched case-control study. RESULTS:
      Seventy-five patients were included (25 VDZ-aTNF, 50 VDZ). Adverse events were
      experienced by 9/25 VDZ-aTNF compared to 13/50 VDZ patients (P = 0.4, follow-up
      14 weeks in all). Week 14 clinical remission was attained in 10/25 (40%) of VDZ
      aTNF patients versus 23/50 (46%) of VDZ patients (OR = 0.8, 95% CI 0.3-2.1, P =
      0.6) and clinical response in 19/25 (76%) versus 39/50 (78%) respectively (OR =
      0.9, 95% CI 0.3-2.7, P = 0.8). Corticosteroid-free remission and corticosteroid
      free response were experienced by 30% and 54%, respectively, of the entire
      cohort, and were similar between the two groups. Vedolizumab drug concentrations
      at week 2, 6 and 14 were similar among VDZ-aTNF and VDZ patients (P > 0.5). Multi
      variable analysis showed independent association of some vedolizumab drug-levels
      time-points with baseline albumin and weight, but not with anti-TNF co-exposure.
      In a prospective study of a separate cohort of patients starting infliximab (n =
      12), the percentage of alpha4beta7+ memory T cells, slightly but nonsignificantly
      increased throughout weeks 0, 2 to 14 (26 +/- 2.3%, 27.8 +/- 2.9%, 29.5 +/- 2.6%
      respectively, P = 0.06). CONCLUSIONS: Vedolizumab/anti-TNF co-exposure did not
      generate new safety signals during 14-weeks induction, nor did it reduce efficacy
      or alter vedolizumab pharmacokinetics. These observations may aid the design of
      future co-biologics trials and also suggest that a deliberate waiting-interval
      between anti-TNF cessation and subsequent vedolizumab initiation may not be
      warranted.

PMID- 29446099
TI  - Mesalazine-induced bullous fixed drug eruption.

PMID- 29446101
TI  - Corrigendum.

PMID- 29446100
TI  - Systemic allergic dermatitis caused by sodium metabisulfite in rectal enemas.

PMID- 29446102
TI  - Phylotype and sequevar of Ralstonia solanacearum which causes bacterial wilt in
      Curcuma alismatifolia Gagnep.
AB  - : Bacterial wilt of Curcuma alismatifolia (Patumma) caused by Ralstonia
      solanacearum is a major disease affecting the quality of rhizome exports.
      Traditionally, R. solanacearum is classified into five races based on differences
      in host range and six biovars based on biochemical properties. Recently a
      classification scheme based on phylotypes and sequevars was presented by the
      scientific community as a tool for determining phylogenetic relationships within
      R. solanacearum. This study used traditional and molecular methods to identify R.
      solanacearum strains from Patumma. All the strains were identified as biovar 4. A
      phylotype-specific multiplex PCR-based phylotyping of all the isolates detected
      the phylotype I-specific amplicon of 144 bp and the R. solanacearum-specific 281
      bp amplicon. Phylogenetic analyses of endoglucanase (egl) sequences clustered all
      three strains of Patumma into phylotype I, sequevar 48 with reference strains M2
      and M6. The study determined that the R. solanacearum strains from Patumma belong
      to biovar 4, phylotype I that originated from Asia, and sequevar 48. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Phylotype and sequevar of Ralstonia solanacearum were
      associated with geographic region and geographic distribution. This is the first
      study to identify phylotype and sequevar of R. solanacearum from Patumma in
      Chiang Mai, Thailand. This will be useful for study of disease epidemiology and
      could help management for control of bacterial wilt diseases in this host.

PMID- 29446104
TI  - Heparin mimetics with anticoagulant activity.
AB  - Heparin, a sulfated polysaccharide belonging to the glycosaminoglycan family, has
      been widely used as an anticoagulant drug for decades and remains the most
      commonly used parenteral anticoagulant in adults and children. However, heparin
      has important clinical limitations and is derived from animal sources which pose
      significant safety and supply problems. The ever growing shortage of the raw
      material for heparin manufacturing may become a very significant issue in the
      future. These global limitations have prompted much research, especially
      following the recent well-publicized contamination scandal, into the development
      of alternative anticoagulants derived from non-animal and/or totally synthetic
      sources that mimic the structural features and properties of heparin. Such
      compounds, termed heparin mimetics, are also needed as anticoagulant materials
      for use in biomedical applications (e.g., stents, grafts, implants etc.). This
      review encompasses the development of heparin mimetics of various structural
      classes, including synthetic polymers and non-carbohydrate small molecules as
      well as sulfated oligo- and polysaccharides, and fondaparinux derivatives and
      conjugates, with a focus on developments in the past 10 years.

PMID- 29446103
TI  - Carfilzomib in relapsed or refractory multiple myeloma patients with early or
      late relapse following prior therapy: A subgroup analysis of the randomized phase
      3 ASPIRE and ENDEAVOR trials.
AB  - We performed analyses of the randomized phase 3 ASPIRE and ENDEAVOR trials to
      investigate the efficacy of carfilzomib among subgroups of relapsed or refractory
      multiple myeloma patients who had early or late disease relapse following
      initiation of the immediately prior therapy. In ASPIRE and ENDEAVOR, patients had
      received 1 to 3 prior lines of therapy. Patients in ASPIRE received carfilzomib,
      lenalidomide, and dexamethasone (KRd) or lenalidomide and dexamethasone (Rd), and
      patients in ENDEAVOR received carfilzomib and dexamethasone (Kd) or bortezomib
      and dexamethasone (Vd). Patients with relapse <=1 year after initiating the most
      recent prior line of therapy were categorized as early relapsers, and patients
      with relapse after >1 year were categorized as late relapsers. The median
      progression-free survival (PFS) in ASPIRE for early relapsers was 21.4 months for
      KRd vs 10.7 months for Rd (hazard ratio [HR]: 0.714; 95% confidence interval
      [CI]: 0.508-1.004; P = 0.0257), and for late relapsers was 29.7 months for KRd vs
      18.2 months for Rd (HR: 0.675; 95% CI: 0.533-0.854; P = 0.0005). The overall
      response rate (ORR) for early relapsers was 83.2% for KRd vs 54.8% for Rd, and
      for late relapsers was 89.0% for KRd vs 69.7% for Rd. The median PFS in ENDEAVOR
      (Kd vs Vd) for early relapsers was 13.9 months vs 5.7 months (HR: 0.598; 95% CI:
      0.423-0.846; P = 0.0017), and for late relapsers was 22.2 months vs 10.2 months
      (HR: 0.486; 95% CI: 0.382-0.620; P < 0.0001). The ORR (Kd vs Vd) for early
      relapsers was 63.4% vs 49.1% and for late relapsers was 81.8% vs 66.8%. In
      conclusion, patients with relapsed or refractory multiple myeloma who received
      carfilzomib-containing regimens had improved PFS and ORR compared with control
      groups, regardless of whether they had an early or late relapse following the
      most recent prior therapy.

PMID- 29446105
TI  - Occupational allergic rhinitis and contact urticaria caused by Gum Arabic in a
      candy factory worker.

PMID- 29446106
TI  - Impact of controlled attenuation parameter on detecting fibrosis using liver
      stiffness measurement.
AB  - BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in
      patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive
      characterisation is of utmost importance. Vibration-controlled transient
      elastography is the non-invasive method of choice; however, recent research
      suggests that steatosis may influence its diagnostic performance. Controlled
      Attenuation Parameter (CAP) added to transient elastography enables simultaneous
      assessment of steatosis and fibrosis. AIM: To determine how to use CAP in
      interpreting liver stiffness measurements. METHODS: This is a secondary analysis
      of data from an individual patient data meta-analysis on CAP. The main exclusion
      criteria for the current analysis were unknown aetiology, unreliable elastography
      measurement and data already used for the same research question. Aetiology
      specific liver stiffness measurement cut-offs were determined and used to
      estimate positive and negative predictive values (PPV/NPV) with logistic
      regression as functions of CAP. RESULTS: Two thousand and fifty eight patients
      fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV,
      51% significant fibrosis >= F2). Youden optimised cut-offs were only sufficient
      for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised
      cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be
      improved slightly through consideration of CAP. PPV for significant fibrosis and
      cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs
      for cirrhosis. CONCLUSIONS: Liver stiffness measurement values below aetiology
      specific cut-offs are very useful for ruling out cirrhosis, and to a lesser
      extent for ruling out significant fibrosis. In the case of the latter, Controlled
      Attenuation Parameter can improve interpretation slightly. Even if cut-offs are
      very high, liver stiffness measurements are not very reliable for ruling in
      fibrosis or cirrhosis.

PMID- 29446107
TI  - Intestinal T-cell lymphoma with enteropathy-associated T-cell lymphoma-like
      features arising in the setting of adult autoimmune enteropathy.
AB  - Enteropathy-associated T-cell lymphoma is regarded as a dismal, late complication
      of coeliac disease, though a single case of T-cell lymphoma with such features
      arising in the setting of autoimmune enteropathy of the adult has been reported
      to date. We aim to describe the case of a 41-year-old woman complaining of severe
      malabsorption syndrome, who was diagnosed with autoimmune enteropathy based on
      the presence of flat intestinal mucosa unresponsive to any dietary restriction
      and positivity for enterocyte autoantibodies. Steroid therapy led to a complete
      recovery of both mucosal and clinical findings over 12 years, when disease
      relapse was accompanied by the appearance of monoclonal rearrangement of T-cell
      receptor-gamma and peculiar T-cell phenotypic abnormalities, leading to a rapid
      transition to an overt T-cell lymphoma with features of the enteropathy
      associated subtype. Despite intensive treatment, the patient developed cerebral
      metastasis and died 9 months later. Our case enhances the concept of enteropathy
      associated T-cell lymphoma as a disease that may arise in the setting of
      enteropathies other than coeliac disease, thus representing a heterogeneous
      entity. Moreover, our observations support the need of a close follow-up of these
      patients, coupled with comprehensive characterization of mucosal biopsies.

PMID- 29446108
TI  - Resilience Analysis of a Remote Offshore Oil and Gas Facility for a Potential
      Hydrocarbon Release.
AB  - Resilience is the capability of a system to adjust its functionality during a
      disturbance or perturbation. The present work attempts to quantify resilience as
      a function of reliability, vulnerability, and maintainability. The approach
      assesses proactive and reactive defense mechanisms along with operational factors
      to respond to unwanted disturbances and perturbation. This article employs a
      Bayesian network format to build a resilience model. The application of the model
      is tested on hydrocarbon-release scenarios during an offloading operation in a
      remote and harsh environment. The model identifies requirements for robust
      recovery and adaptability during an unplanned scenario related to a hydrocarbon
      release. This study attempts to relate the resilience capacity of a system to the
      system's absorptive, adaptive, and restorative capacities. These factors
      influence predisaster and postdisaster strategies that can be mapped to enhance
      the resilience of the system.

PMID- 29446109
TI  - Systematic review: the natural history of alpha-1 antitrypsin deficiency, and
      associated liver disease.
AB  - BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is estimated to affect three
      million people worldwide. It causes liver disease in a proportion of carriers of
      the PiS and PiZ allele due to the formation and retention of polymers within the
      endoplasmic reticulum of hepatocytes. The reason for this selective penetrance is
      not known. Although clinical trials are underway, liver transplantation is the
      only effective treatment for liver disease due to AATD. AIMS: To report the
      prevalence and natural history of liver disease among individuals with AATD, and
      assess the outcomes of liver transplantation through systematic review. METHODS:
      A comprehensive search was conducted across multiple databases. Two independent
      authors selected the articles and assessed bias using the Newcastle-Ottawa Scale.
      Data were pooled for analysis, where comparable outcomes were reported. RESULTS:
      Thirty-five studies were identified related to disease progression and 12 for the
      treatment of AATD. Seven per cent of children were reported to develop liver
      cirrhosis, with 16.5% of individuals presenting in childhood requiring liver
      transplantation. Of those surviving to adulthood, 10.5% had liver cirrhosis and
      14.7% required transplantation. Liver transplantation was the only effective
      treatment reported and outcomes compare favourably to other indications, with 5
      year survival reported as over 90% in children and over 80% in adults.
      DISCUSSION: The clinical course of liver disease in individuals with AATD remains
      poorly understood, but affects about 10% of those with AATD. More research is
      required to identify those patients at risk of developing liver disease at an
      early stage, and to provide alternative treatments to liver transplantation.

PMID- 29446110
TI  - Contact allergy to a meteorite: An interesting consequence of nickel allergy.

PMID- 29446111
TI  - Garment allergy caused by Disperse Blue 360: A new sensitizer.

PMID- 29446112
TI  - Variability in Cross-Domain Risk Perception among Smallholder Farmers in Mali by
      Gender and Other Demographic and Attitudinal Characteristics.
AB  - Previous research has shown that men and women, on average, have different risk
      attitudes and may therefore see different value propositions in response to new
      opportunities. We use data from smallholder farm households in Mali to test
      whether risk perceptions differ by gender and across domains. We model this
      potential association across six risks (work injury, extreme weather, community
      relationships, debt, lack of buyers, and conflict) while controlling for
      demographic and attitudinal characteristics. Factor analysis highlights extreme
      weather and conflict as eliciting the most distinct patterns of participant
      response. Regression analysis for Mali as a whole reveals an association between
      gender and risk perception, with women expressing more concern except in the
      extreme weather domain; however, the association with gender is largely absent
      when models control for geographic region. We also find lower risk perception
      associated with an individualistic and/or fatalistic worldview, a risk-tolerant
      outlook, and optimism about the future, while education, better health, a social
      orientation, self-efficacy, and access to information are generally associated
      with more frequent worry-with some inconsistency. Income, wealth, and time
      poverty exhibit complex associations with perception of risk. Understanding
      whether and how men's and women's risk preferences differ, and identifying other
      dominant predictors such as geographic region and worldview, could help
      development organizations to shape risk mitigation interventions to increase the
      likelihood of adoption, and to avoid inadvertently making certain subpopulations
      worse off by increasing the potential for negative outcomes.

PMID- 29446113
TI  - Use of a Simple, Inexpensive Dual-Modality Phantom as a Learning Tool for
      Magnetic Resonance Imaging-Ultrasound Fusion Techniques.
AB  - We describe an easily constructed, customizable phantom for magnetic resonance
      imaging-ultrasound fusion imaging and demonstrate its role as a learning tool to
      initiate clinical use of this emerging modality. Magnetic resonance imaging
      ultrasound fusion can prove unwieldy to integrate into routine practice. We
      demonstrate real-time fusion with single-sequence magnetic resonance imaging
      uploaded to the ultrasound console. Phantom training sessions allow radiologists
      and sonographers to practice fiducial marker selection and improve efficiency
      with the fusion hardware and software interfaces. Such a tool is useful when the
      modality is first introduced to a practice and in settings of sporadic use, in
      which intermittent training may be useful.

PMID- 29446114
TI  - A Rare Case of Prenatally Diagnosed Arterial Tortuosity.

PMID- 29446115
TI  - Iatrogenic risk factors associated with hospital readmission of elderly patients:
      A matched case-control study using a clinical data warehouse.
AB  - WHAT IS KNOWN: Hospital readmission within 30 days of patient discharge has
      become a standard to judge the quality of hospitalizations. It is estimated that
      14% of the elderly, people over 75 years old or those over 65 with comorbidities,
      are at risk of readmission, of which 23% are avoidable. It may be possible to
      identify elderly patients at risk of readmission and implement steps to reduce
      avoidable readmissions. OBJECTIVE: The aim of this study was to identify
      iatrogenic risk factors for readmission. The secondary objective was to evaluate
      the rate of drug-related readmissions (DRRs) among all readmissions and compare
      it to the rate of readmissions for other reasons. METHODS: We conducted a
      retrospective, matched, case-control study to identify non-demographic risk
      factors for avoidable readmission, specifically DRRs. The study included patients
      hospitalized between 1 September 2014 and 31 October 2015 in an 800-bed
      university hospital. We included patients aged 75 and over. Cases consisted of
      patients readmitted to the emergency department within 30 days of initial
      discharge. Controls did not return to the emergency department within 30 days.
      Cases and controls were matched on sex and age because they are known as
      readmissions risk factors. After comparison of the mean or percentage between
      cases and controls for each variable, we conducted a conditional logistic
      regression. RESULTS: The risk factors identified were an emergency admission at
      the index hospitalization, returning home after discharge, a history of unplanned
      readmissions and prescription of nervous system drugs. Otherwise, 11.4% of the
      readmissions were DRRs, of which 30% were caused by an overdose of
      antihypertensive. The number of drugs at readmission was higher, and potentially
      inappropriate medications were more widely prescribed for DRRs than for
      readmissions for other reasons. WHAT IS NEW AND CONCLUSION: In this matched case
      control retrospective study, after controlling for gender and age, we identified
      the typical profile of elderly patients at risk of readmission. These patients
      had an unplanned admission at the index hospitalization and prescribed nervous
      system drugs at discharge from the index admission; they have a history of
      unplanned readmission within 30 days and return home after discharge.

PMID- 29446116
TI  - Does integrated academic and health education prevent substance use? Systematic
      review and meta-analyses.
AB  - BACKGROUND: Prevention of substance (alcohol, tobacco, illegal/legal drug) use in
      adolescents is a public health priority. As the scope for school-based health
      education is constrained in school timetables, interventions integrating academic
      and health education have gained traction in the UK and elsewhere, though
      evidence for their effectiveness remains unclear. We sought to synthesize the
      effectiveness of interventions integrating academic and health education for the
      prevention of substance use. METHODS: We searched 19 databases between November
      and December 2015, among other methods. We included randomized trials of
      interventions integrating academic and health education targeting school students
      aged 4-18 and reporting substance use outcomes. We excluded interventions for
      specific health-related subpopulations (e.g., children with behavioural
      difficulties). Data were extracted independently in duplicate. Outcomes were
      synthesized by school key stage (KS) using multilevel meta-analyses, for
      substance use, overall and by type. RESULTS: We identified 7 trials reporting
      substance use. Interventions reduced substance use generally in years 7-9 (KS3)
      based on 5 evaluations (d = -0.09, 95% CI [-0.17, -0.01], I2  = 35%), as well as
      in years 10-11 (KS4) based on 3 evaluations (-0.06, [-0.09, -0.02]; I2  = 0%).
      Interventions were broadly effective for reducing specific alcohol, tobacco, and
      drug use in both KS groups. CONCLUSIONS: Evidence quality was highly variable.
      Findings for years 3-6 and 12-13 could not be meta-analysed, and we could not
      assess publication bias. Interventions appear to have a small but significant
      effect reducing substance use. Specific methods of integrating academic and
      health education remain poorly understood.

PMID- 29446118
TI  - Water suppression in the human brain with hypergeometric RF pulses for single
      voxel and multi-voxel MR spectroscopy.
AB  - PURPOSE: To develop and investigate a novel water suppression sequence with
      hypergeometric pulses at 3 T. METHODS: Simulations were used to optimize the
      delays and amplitudes of 5 hypergeometric prepulses, to minimize the residual
      water over a range of T1 and B1 values. Single-voxel data with hypergeometric
      water suppression (HGWS) prepulses were acquired in the centrum semiovale, 2
      parietal regions, and insula of 7 subjects, and compared with VAPOR water
      suppression. Magnetic resonance spectroscopic imaging (MRSI) data using both
      VAPOR and HGWS prepulses were also collected and compared. Water suppression
      performance was calculated as the residual water peak height relative to the
      unsuppressed water peak. MRSI voxel-by-voxel comparison was performed by
      calculating the ratio between HGWS and VAPOR residual water peaks. RESULTS: In
      simulations, HGWS and VAPOR are insensitive to B1 and water T1 variations, but
      with no B1 variation, HGWS has a lower average residual water fraction (0.0033)
      than that of VAPOR (0.0091). In single-voxel acquisitions, HGWS performs better
      than VAPOR in all regions with a 2.3-fold to 5.7-fold lower residual water. In
      MRSI acquisitions, HGWS performs on average 2.3-fold better than VAPOR in 98.9%
      of the voxels. CONCLUSION: HGWS provides better water suppression than VAPOR in
      both single-voxel and multivoxel acquisitions with a shorter sequence duration.

PMID- 29446119
TI  - Pancreaticoduodenal arterial arcades: Their dominance and variations-their
      potential clinical relevance.
AB  - The complex arterial system makes pancreatic interventions technically
      challenging for surgeons, and interventional radiologists. The arterial variants
      may alter tumor resecability, and cause complications in arterial embolization.
      International data on pancreatic blood supply are variable; therefore, we aimed
      to determine the frequency of variants of pancreaticoduodenal (PD) arterial
      arcades. Arteries of human abdominal organ complexes (50) were injected with
      resin mixture, and then corroded. CT scans and three-dimensional reconstructions
      were made; diameters of arcades were measured. Two PD arcades were found in 58%,
      three arcades in 30%, one arcade in three cases, four arcade in one specimen, and
      five arcades in two cases. In the casts with two arches the average diameter was
      1.472 +/- 0.432 mm on the anterior and 1.383 +/- 0.343 mm on the posterior arch.
      Assessing the dominance of the PD arcades, the anterior arch proved to be
      dominant in 52% of the cases, and in 35% the posterior one by the criterion of
      25% cross-section difference. It is advised to analyze the variations and
      dominance on a CT/MR-angiography before local chemotherapy. Furthermore, to
      reveal the arterial variations, a preoperative CT/MR-angiography would provide
      faster recuperation and better postoperative life quality. Clin. Anat. 31:544
      550, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29446120
TI  - A novel case of a brush with discomfort: allergic contact dermatitis caused by
      mercaptobenzothiazole in rubber components of a toothbrush.

PMID- 29446117
TI  - The sociology of cancer: a decade of research.
AB  - Biomedicine is often presented as the driving force behind improvements in cancer
      care, with genomics the latest innovation poised to change the meaning,
      diagnosis, treatment, prevention and lived experience of cancer. Reviewing
      sociological analyses of a diversity of patient and practitioner experiences and
      accounts of cancer during the last decade (2007-17), we explore the experiences
      of, approaches to and understandings of cancer in this period. We identify three
      key areas of focus: (i) cancer patient experiences and identities; (ii) cancer
      risk and responsibilities and (iii) bioclinical collectives. We explore these
      sociological studies of societal and biomedical developments and how sociologists
      have sought to influence developments in cancer identities, care and research. We
      end by suggesting that we extend our understanding of innovations in the fields
      of cancer research to take better account of these wider social and cultural
      innovations, together with patients, activists' and sociologists' contributions
      therein.

PMID- 29446121
TI  - Atrophy of hip abductor muscles is related to clinical severity in a hip
      osteoarthritis population.
AB  - Osteoarthritis mainly affects weight-bearing joints such as the hip and knee and
      is the most common form of arthritis. Greater muscle atrophy with fatty
      infiltration of gluteal muscles and decreased hip abduction strength has
      previously been identified with increasing severity of radiological hip OA.
      However, it is well documented that radiographic findings of OA do not always
      correlate with clinical severity. The aim of this secondary analysis was to
      examine whether atrophy and strength of gluteus maximus (GMax), medius (GMed),
      minimus (GMin), and tensor fascia lata (TFL) is associated with the clinical
      severity of OA. Twenty participants with unilateral hip OA and 20 age- and sex
      matched asymptomatic controls were classified on the basis of clinical severity
      (mild, moderate-severe and asymptomatic groups) using the Oxford hip score.
      Muscle volumes of GMax, GMed, GMin, and TFL were determined using magnetic
      resonance imaging and expressed as asymmetry between limbs. A hand-held
      dynamometer was used to identify hip rotation and abduction strength. Regression
      analyzes were used to identify the association between muscle asymmetry and
      patient-reported severity of hip OA. Both symptomatic groups (mild and moderate
      severe) demonstrated significant asymmetry in GMax (P < 0.01) and GMin (P <
      0.01). GMed asymmetry was associated with only the moderate-severe symptomatic
      group. Hip abduction strength was reduced in both symptomatic groups. Gluteal
      muscle atrophy was associated with the clinical severity of OA. Clinical severity
      could be a useful tool for clinicians interpreting likely gluteal muscle changes
      and planning rehabilitation strategies for hip OA patients. Clin. Anat. 31:507
      513, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29446122
TI  - Pyogenic granuloma-like Kaposi's sarcoma on the first toe.

PMID- 29446123
TI  - Associations between CSF cortisol and CSF norepinephrine in cognitively normal
      controls and patients with amnestic MCI and AD dementia.
AB  - OBJECTIVE: This study evaluated the effects of Alzheimer disease (AD) on the
      relationship between the brain noradrenergic system and hypothalamic pituitary
      adrenocortical axis (HPA). Specifically, relationships between cerebrospinal
      fluid (CSF) norepinephrine (NE) and CSF cortisol were examined in cognitively
      normal participants and participants with AD dementia and amnestic mild cognitive
      impairment (aMCI). We hypothesized that there would a positive association
      between these 2 measures in cognitively normal controls and that this association
      would be altered in AD. METHODS: Four hundred twenty-one CSF samples were assayed
      for NE and cortisol in controls (n = 305), participants with aMCI (n = 22), and
      AD dementia (n = 94). Linear regression was used to examine the association
      between CSF cortisol and NE, adjusting for age, sex, education, and body mass
      index. RESULTS: Contrary to our hypothesis, CSF cortisol and NE levels were not
      significantly associated in controls. However, higher cortisol levels were
      associated with higher NE levels in AD and aMCI participants. Regression
      coefficients +/- standard errors for the change in cortisol per 100-pg/mL
      increase in NE are as follows: controls 0.0 +/- 0.2, P = 1.0; MCI, 1.4 +/- 0.7, P
      = .14; and AD 1.1 +/- 0.4, P = .032. Analysis with MCI and AD participants
      combined strengthened statistical significance (1.2 +/- 0.3, P = .007).
      CONCLUSIONS: Enhanced responsiveness of the HPA axis to noradrenergic stimulatory
      regulation in AD and disruption of the blood brain barrier may contribute to
      these findings. Because brainstem noradrenergic stimulatory regulation of the HPA
      axis is substantially increased by both acute and chronic stress, these findings
      are also consistent with AD participants experiencing higher levels of acute and
      chronic stress.

PMID- 29446124
TI  - Using oral health assessment to predict aspiration pneumonia in older adults.
AB  - OBJECTIVE: To investigate the significance of comprehensive assessment of oral
      health using the revised oral assessment guide (ROAG) in older adults with
      pneumonia. BACKGROUND: Oral health plays a major role in the eating-swallowing
      process. The role of comprehensive assessment of oral health in older adults with
      aspiration pneumonia has not been evaluated in detail. The ROAG is a screening
      tool for comprehensive assessment and has been shown to have a high sensitivity
      and specificity for the assessment of oral health. MATERIALS AND METHODS: We
      retrospectively studied 238 adults with pneumonia, aged 65 years and above, in
      whom the ROAG score had been assessed between December 2014 and June 2016.
      Participants were divided into two groups based on aspiration risk, as defined by
      Marik et al; correlation between the ROAG score and the risk of aspiration was
      evaluated. RESULTS: Two hundred and fifteen adults (90.3%) were found to be at
      aspiration risk. According to the ROAG score, mild-to-moderate and severe oral
      problems were noted in 38 (16.0%) and 200 (84.0%) adults, respectively.
      Aspiration risk was noted in 68.4% and 94.5% of adults with mild-to-moderate and
      severe oral problems, respectively (P < .0001). The area under the receiver
      operating characteristics curve for ROAG to predict aspiration risk was 0.72 (95%
      confidence interval: 0.60-0.84). Furthermore, a high ROAG score was an
      independent predictor of aspiration risk in our study population. CONCLUSION: In
      clinical practice, oral health assessment using ROAG can help predict aspiration
      risk in older adults with pneumonia.

PMID- 29446125
TI  - Feasibility of high spatiotemporal resolution for an abbreviated 3D radial breast
      MRI protocol.
AB  - PURPOSE: To develop a volumetric imaging technique with 0.8-mm isotropic
      resolution and 10-s/volume rate to detect and analyze breast lesions in a
      bilateral, dynamic, contrast-enhanced MRI exam. METHODS: A local low-rank
      temporal reconstruction approach that also uses parallel imaging and spatial
      compressed sensing was designed to create rapid volumetric frame rates during a
      contrast-enhanced breast exam (vastly undersampled isotropic projection [VIPR]
      spatial compressed sensing with temporal local low-rank [STELLR]). The dynamic
      enhanced data are subtracted in k-space from static mask data to increase
      sparsity for the local low-rank approach to maximize temporal resolution. A T1 
      weighted 3D radial trajectory (VIPR iterative decomposition with echo asymmetry
      and least squares estimation [IDEAL]) was modified to meet the data acquisition
      requirements of the STELLR approach. Additionally, the unsubtracted enhanced data
      are reconstructed using compressed sensing and IDEAL to provide high-resolution
      fat/water separation. The feasibility of the approach and the dual reconstruction
      methodology is demonstrated using a 16-channel breast coil and a 3T MR scanner in
      6 patients. RESULTS: The STELLR temporal performance of subtracted data matched
      the expected temporal perfusion enhancement pattern in small and large vascular
      structures. Differential enhancement within heterogeneous lesions is demonstrated
      with corroboration from a basic reconstruction using a strict 10-second temporal
      footprint. Rapid acquisition, reliable fat suppression, and high spatiotemporal
      resolution are presented, despite significant data undersampling. CONCLUSION: The
      STELLR reconstruction approach of 3D radial sampling with mask subtraction
      provides a high-performance imaging technique for characterizing enhancing
      structures within the breast. It is capable of maintaining temporal fidelity,
      while visualizing breast lesions with high detail over a large FOV to include
      both breasts.

PMID- 29446126
TI  - Layer-specific global longitudinal strain reveals impaired cardiac function in
      patients with reversible ischemia.
AB  - AIMS: Two-dimensional speckle tracking echocardiography (2DSTE) detects early
      signs of left ventricular dysfunction; however, it is unknown whether layer
      specific global longitudinal strain (GLS) has incremental value in diagnosis of
      patients with reversible ischemia assessed by single photon emission computed
      tomography (SPECT). METHODS AND RESULTS: Eighty patients with stable angina
      pectoris (SAP), normal left ventricular ejection fraction (LVEF), and no history
      of ischemic heart disease were retrospectively identified to have been examined
      by 2DSTE, SPECT, and coronary angiography (CAG). Patients with a normal SPECT
      constituted the control group, and patients with a positive SPECT were divided
      into patients with or without (true- or false- positive SPECT) significant
      stenosis assessed by CAG. GLS was measured for two myocardial layers (endocardial
      and epicardial) and as well as mid-myocardial GLS. Patients with reversible
      ischemia had significantly lower GLS compared to the control group
      (GLSEndocardial : -19.0 +/- 4.4% vs -21.4 +/- 3.7%, P = .011; GLSEpicardial : 
      14.3 +/- 2.9% vs -16.3 +/- 2.9%, P = .004); GLSMid-myocardial : -16.5 +/- 3.6% vs
      -18.6 +/- 3.2%, P = .006. This difference was even more evident in patients with
      a true-positive SPECT (GLSEndocardial : -18.0 +/- 4.4% vs -21.4 +/- 3.7%, P <
      .001; GLSEpicardial : -13.6 +/- 3.0% vs -16.3 +/- 2.9%, P < .001); GLSMid
      myocardial : -15.6 +/- 3.6% vs -18.6 +/- 3.2%, P < .001. Notably, no significant
      differences existed in patients with a false-positive SPECT. GLSEpicardial was
      the only independent predictor of coronary artery disease. IN CONCLUSION: In
      patients with SAP and preserved LVEF, layer-specific GLS at rest identifies
      patients with reversible ischemia. This seems to be evident only in patients with
      a true-positive SPECT, thus, 2DSTE at rest might improve the diagnostic accuracy
      of a positive SPECT.

PMID- 29446128
TI  - Editorial: restoring therapeutic infliximab drug levels in patients with loss of
      response-pharmacokinetics and anti-drug antibodies as useful guidance tools.

PMID- 29446129
TI  - Editorial: infliximab trough levels and histological healing in ulcerative
      colitis-a step towards personalised biologic therapy.

PMID- 29446127
TI  - Whole-body MRI for metastatic cancer detection using T2 -weighted imaging with
      fat and fluid suppression.
AB  - PURPOSE: To develop a whole-body MRI technique at 3T with improved lesion
      conspicuity for metastatic cancer detection using fast, high-resolution and high
      SNR T2 -weighted (T2 W) imaging with simultaneous fat and fluid suppression.
      THEORY AND METHODS: The proposed dual-echo T2 -weighted acquisition for enhanced
      conspicuity of tumors (DETECT) acquires 4 images, in-phase (IP) and out-of-phase
      (OP) at a short and a long TE using single-shot turbo spin echo. The IP/OP images
      at the short and long TEs are reconstructed using the standard Dixon and shared
      field-map Dixon reconstruction respectively, for robust fat-water separation. An
      adaptive complex subtraction between the 2 TE water-only images achieves fluid
      attenuation. DETECT imaging was optimized and evaluated in whole-body imaging of
      5 healthy volunteers, and compared against diffusion-weighted imaging with
      background suppression (DWIBS) in 5 patients with known metastatic renal cell
      carcinoma. RESULTS: Robust fat-water separation and fluid attenuation were
      achieved using the shared-field-map Dixon reconstruction and adaptive complex
      subtraction, respectively. DETECT imaging technique generated co-registered T2 W
      images with and without fat suppression, heavily T2 W, and fat and fluid
      suppressed T2 W whole-body images in <7 min. Compared to DWIBS acquired in 17
      min, the DETECT imaging achieved better detection and localization of lesions in
      patients with metastatic cancer. CONCLUSION: DETECT imaging technique generates
      T2 W images with high resolution, high SNR, minimal geometric distortions, and
      provides good lesion conspicuity with robust fat and fluid suppression in <7 min
      for whole-body imaging, demonstrating efficient and reliable metastatic cancer
      detection at 3T.

PMID- 29446130
TI  - Editorial: the post-Helicobacter stomach-not the same for cohorts and
      individuals.

PMID- 29446131
TI  - Editorial: the portal hypertension puzzle-spleen stiffness evades validation as
      non-invasive marker of clinically significant portal hypertension.

PMID- 29446132
TI  - Letter: mucosal response in discriminating intestinal tuberculosis from Crohn's
      disease-when to look for it?

PMID- 29446133
TI  - Editorial: are additional tests needed to predict sustained virologic response in
      hepatitis C treated with interferon-free direct-acting antiviral combinations?
      Authors' reply.

PMID- 29446134
TI  - Editorial: biologic therapy for chronic pouchitis - are we beginning to meet the
      unmet need?

PMID- 29446135
TI  - Letter: high oral dose of taurine for portal hypertension in cirrhotic patients
      some clinical pharmacology considerations.

PMID- 29446136
TI  - Editorial: the post-Helicobacter stomach-not the same for cohorts and
      individuals. Authors' reply.

PMID- 29446137
TI  - Letter: mucosal response in discriminating intestinal tuberculosis from Crohn's
      disease-when to look for it? Authors' reply.

PMID- 29446138
TI  - Editorial: sofosbuvir plus daclatasvir for the treatment of hepatitis C-can one
      size fit all?

PMID- 29446139
TI  - Editorial: macrophage activation markers predict prognosis and decompensation in
      patients with cirrhosis-linking gut permeability, inflammation and cirrhosis
      progression.

PMID- 29446140
TI  - Corrigendum.

PMID- 29446141
TI  - Editorial: nocebo effect and switching to biosimilars.

PMID- 29446142
TI  - Corrigendum.

PMID- 29446143
TI  - Editorial: are additional tests needed to predict sustained virologic response in
      hepatitis C treated with interferon-free direct-acting antiviral combinations?

PMID- 29446144
TI  - Animal models of multiple sclerosis: Focus on experimental autoimmune
      encephalomyelitis.
AB  - Multiple sclerosis (MS) is a chronic, progressive disorder of the central nervous
      system (CNS) that affects more than two million people worldwide. Several animal
      models resemble MS pathology; the most employed are experimental autoimmune
      encephalomyelitis (EAE) and toxin- and/or virus-induced demyelination. In this
      review we will summarize our knowledge on the utility of different animal models
      in MS research. Although animal models cannot replicate the complexity and
      heterogeneity of the MS pathology, they have proved to be useful for the
      development of several drugs approved for treatment of MS patients. This review
      focuses on EAE because it represents both clinical and pathological features of
      MS. During the past decades, EAE has been effective in illuminating various
      pathological processes that occur during MS, including inflammation, CNS
      penetration, demyelination, axonopathy, and neuron loss mediated by immune cells.

PMID- 29446145
TI  - Neuronal ceroid lipofuscinosis in Salukis is caused by a single base pair
      insertion in CLN8.
AB  - Neuronal ceroid lipofuscinoses (NCLs) are heterogenic inherited lysosomal storage
      diseases that have been described in a number of species including humans, sheep,
      cattle, cats and a number of different dog breeds, including Salukis. Here we
      present a novel genetic variant associated with the disease in this particular
      breed of dog. In a clinical case, a Saluki developed progressive neurological
      signs, including disorientation, anxiety, difficulties in eating, seizures and
      loss of vision, and for welfare reasons, was euthanized at 22 months of age.
      Microscopy showed aggregation of autofluorescent storage material in the neurons
      of several brain regions and also in the retina. The aggregates showed positive
      staining with Sudan black B and periodic acid Schiff, all features consistent
      with NCL. Whole genome sequencing of the case and both its parents, followed by
      variant calling in candidate genes, identified a new variant in the CLN8 gene: a
      single bp insertion (c.349dupT) in exon 2, introducing an immediate stop codon
      (p.Glu117*). The case was homozygous for the insertion, and both parents were
      heterozygous. A retrospective study of a Saluki from Australia diagnosed with NCL
      identified this case as being homozygous for the same mutation. This is the
      fourth variant identified in CLN8 that causes NCL in dogs.

PMID- 29446146
TI  - CRISPR/Cas9-mediated MSTN disruption and heritable mutagenesis in goats causes
      increased body mass.
AB  - Genetic engineering in livestock has been greatly enhanced through the use of
      artificial programmed nucleases such as the recently emerged clustered regularly
      interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system.
      We recently reported our successful application of the CRISPR/Cas9 system to
      engineer the goat genome through micro-injection of Cas9 mRNA and sgRNAs
      targeting MSTN and FGF5 in goat embryos. The phenotypes induced by edited loss-of
      function mutations of MSTN remain to be evaluated extensively. We demonstrate the
      utility of this approach by disrupting MSTN, resulting in enhanced body weight
      and larger muscle fiber size in Cas9-mediated gene-modified goats. The effects of
      genome modifications were further characterized by H&E staining, quantitative
      PCR, Western blotting and immunofluorescence staining. Morphological and genetic
      analyses indicated the occurrence of phenotypic and genotypic modifications. We
      further provide sufficient evidence, including breeding data, to demonstrate the
      transmission of the knockout alleles through the germline. By phenotypic and
      genotypic characterization, we demonstrated the merit of using the CRISPR/Cas9
      approach for establishing genetically modified livestock with an enhanced
      production trait.

PMID- 29446147
TI  - Successful treatment of chronic intractable pain with risperidone in a patient
      with acquired idiopathic generalized anhidrosis.

PMID- 29446148
TI  - Efficacy of low-dose 5-fluorouracil/cisplatin therapy for invasive extramammary
      Paget's disease.
AB  - Extramammary Paget's disease (EMPD) is one of the cutaneous adenocarcinomas. The
      effective chemotherapy for advanced EMPD has not been established. This study was
      designed to evaluate the efficacy of combination 5-fluorouracil (500 mg/body, 7
      days/week) and cisplatin (5 mg/body 5 days/week) for invasive EMPD. Seventeen
      EMPD patients with multiple metastases who visited our dermatology clinic between
      October 2004 and May 2016 (mean age, 76.9 years; 10 men, seven women) were
      retrospectively analyzed. Eight EMPD patients underwent low-dose 5
      fluorouracil/cisplatin therapy and nine patients chose best supportive care. The
      average number of treatment cycles was 12.3. All patients had a confirmed
      response, four (50%) showed a partial response, two (25%) stable disease and two
      progressive disease. The median times to progression-free and overall survival
      were 25.0 and 77.4 weeks, respectively. There was no severe (grade 3 and 4)
      adverse event. Although not significant, the survival of the patients treated
      with low-dose 5-fluorouracil/cisplatin therapy showed a trend toward improved
      survival as compared with best supportive care (P = 0.08, log-rank test). This
      regimen had low risk and relatively high disease control rate, suggesting that
      this regimen be recommended as one of the treatment options for advanced EMPD.

PMID- 29446149
TI  - Distinction of the GABA 2.29 ppm resonance using triple refocusing at 3 T in
      vivo.
AB  - PURPOSE: To develop 1 H MR spectroscopy that provides distinction of gamma
      aminobutyric acid (GABA) signal at 3 T in vivo. METHODS: Triple-refocusing was
      tailored at 3 T, with numerical simulations and phantom validation, for
      distinction of the GABA 2.29-ppm resonance from the neighboring glutamate
      resonance. The optimization was performed on the inter-RF pulse time delays and
      the duration and carrier frequency of a non-slice-selective RF pulse. The
      optimized triple refocusing was tested in multiple regions in 6 healthy subjects,
      including hippocampus. The in vivo spectra were analyzed with the LCModel using
      in-house basis spectra. After normalization of the metabolite signal estimates to
      water, the metabolite concentrations were quantified with reference to medial
      occipital creatine at 8 mM. RESULTS: A triple-refocusing scheme with optimized
      inter-RF pulse time delays (TE = 74 ms) was obtained for GABA detection. With
      optimized duration (14 ms) and carrier frequency (4.5 ppm) of the non-slice
      selective RF pulse, the triple refocusing gave rise to distinction between the
      GABA 2.29-ppm and glutamate 2.35-ppm signals. The GABA 2.29-ppm signal was
      clearly discernible in spectra in vivo (voxel size 4 to 12 mL; scan times 4.3 to
      17 minutes). With a total of 24 spectra from 6 gray or white matter-dominant
      regions, the GABA concentration was measured to be 0.62 to 1.15 mM (Cramer-Rao
      lower bound of 8 to 14%), and the glutamate level 5.8 to 11.2 mM (Cramer-Rao
      lower bound of 3 to 6%). CONCLUSION: The optimized triple refocusing provided
      distinction between GABA and glutamate signals and permitted direct codetection
      of these metabolites in the human brain at 3 T in vivo.

PMID- 29446150
TI  - Antimicrobial peptide gene expression in periodontitis patients: A pilot study.
AB  - AIM: Antimicrobial peptides (AMPs) are one of the most active components of
      innate immunity and have characteristics that could place them at the heart of
      the pathogenesis of periodontal disease. This study investigated differences in
      the expression of AMP coding genes obtained using a simple harvesting technique,
      gingival smear, between two groups of patients: chronic periodontitis subjects
      versus healthy ones. MATERIALS AND METHODS: Twenty-three patients were enrolled
      in two groups: 12 were diagnosed with moderate or severe generalized chronic
      periodontitis, and 11 were diagnosed as clinically healthy. Gingival smears were
      retrieved and studied using reverse transcription-quantitative PCR (RT-qPCR)
      after mRNA purification. RESULTS: Fifteen gene expressions were obtained using
      real-time RT-qPCR. Three AMP genes, histatin 3 (HTN3), alpha-defensin 4 (DEFA4)
      and lysozyme C (LYZ), presented different expression levels in periodontitis
      patients compared with healthy subjects. The relative expression level of DEFA4
      appeared to be a protective factor against periodontitis. CONCLUSION: Gingival
      smears studied by RT-qPCR may be used to assess the expression of AMPs coding
      genes. A lack of expression of DEFA4 could be a potential indicator of
      periodontitis status.

PMID- 29446151
TI  - Organisational framework and outputs of International medical evacuation in
      Guinea: A need for change.
AB  - The study aims to describe the organizational framework of International Medical
      Evacuation (IME), the profile of persons evacuated, and the associated cost of
      IME in Guinea. This was a descriptive study of IME policy in Guinea. We described
      the politico-structural organization of IME and the profile of patient accessing
      IME through the Ministry of Health (MOH: 2001-2015) and through the National
      Social Security Fund (NSSF: 2011-2015). From 1958 to 1992 since the health system
      was restricted, the country negotiated the free medical treatment with Socialist
      countries. Since 1992, a medical assistance line was included in the sector
      budgets, and IME was officially managed by the MOH and with a parallel system
      existing at the NSSF. With an average cost of US $34 251 per case, cardiovascular
      diseases (20%), Traumatology/Orthopedic diseases (20%), and
      Neurologic/neurosurgery diseases (12.5%) have motivated more than half of 2445
      IME supported by the MOH between 2001 and 2015. With a diagnostic exploration
      (38.7%) as main motivation, the majority of the IMEs (80.0%) endorsed by the NSSF
      (2011-2015) concerned their employees/workers or those of the NSSF's supervisory
      ministry and their families. Despite a strict regulatory framework, the emergence
      and sustainability of parallel IME systems in other departments with different
      procedures than MOH's procedure represent a major weakness/deficiency. The new
      prospects for the free medical treatment of state employees could eventually lead
      to an effective correction of this structural failure if efficiently managed.

PMID- 29446152
TI  - Loss of philological purity: Hybrid vigor or mongrelism?
AB  - Although disparaged by philologists, hybrid words enrich technical and scientific
      vocabularies. They are common, so, like it or not, they are here to stay. On the
      other hand, where there are pre-existing purebred compound or affixed words, they
      should generally be given preference over hybrids. Some adjectives (e.g.,
      laryngeus and sphenoideus) are discussed to illustrate these recommendations.
      Clin. Anat. 31:771-773, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29446153
TI  - Eating fish and farm life reduce allergic rhinitis at the age of twelve.
AB  - BACKGROUND: The prevalence of allergic rhinitis has increased, but the cause of
      this rise is partly unknown. Our aim was to analyse the prevalence, risk factors,
      and protective factors for allergic rhinitis in 12-year-old Swedish children.
      METHODS: Data were collected from a prospective, longitudinal cohort study of
      children born in western Sweden in 2003. The parents answered questionnaires when
      the children were 6 months to 12 years. The response rate at 12 years was 76%
      (3637/4777) of the questionnaires distributed. RESULTS: At the age of 12, 22% of
      children had allergic rhinitis and 57% were boys. Mean age at onset was 7.8
      years, and 55% reported their first symptoms after 8 years. The most common
      trigger factors were pollen (85%), furry animals (34%), and house dust mites
      (17%). A multivariate analysis showed that the adjusted odds ratios and 95%
      confidence intervals for the independent risk factors for allergic rhinitis at 12
      were as follows: parental allergic rhinitis (2.32, 1.94-2.77), doctor-diagnosed
      food allergy in the first year (1.75, 1.21-2.52), eczema in the first year (1.61,
      1.31-1.97), and male gender (1.25, 1.06-1.47). Eating fish once a month or more
      at age of 12 months reduced the risk of allergic rhinitis at 12 years of age
      (0.70, 0.50-0.98) as did living on a farm with farm animals at 4 years (0.51,
      0.32-0.84). Continuous farm living from age 4 to 12 seemed to drive the
      association. CONCLUSIONS: Allergic rhinitis affected > 20% of 12-year-olds, but
      was lower in children who ate fish at 12 months or grew up on a farm with farm
      animals.

PMID- 29446154
TI  - The strategies of alcohol industry SAPROs: Inaccurate information, misleading
      language and the use of confounders to downplay and misrepresent the risk of
      cancer.

PMID- 29446155
TI  - Not just trust: factors influencing learners' attempts to perform technical
      skills on real patients.
AB  - CONTEXT: As part of their training, physicians are required to learn how to
      perform technical skills on patients. The previous literature reveals that this
      learning is complex and that many opportunities to perform these skills are not
      converted into attempts to do so by learners. This study sought to explore and
      understand this phenomenon better. METHODS: A multi-phased qualitative study
      including ethnographic observations, interviews and focus groups was conducted to
      explore the factors that influence technical skill learning. In a tertiary
      paediatric emergency department, staff physician preceptors, residents, nurses
      and respiratory therapists were observed in the delivery and teaching of
      technical skills over a 3-month period. A constant comparison methodology was
      used to analyse the data and to develop a constructivist grounded theory.
      RESULTS: We conducted 419 hours of observation, 18 interviews and four focus
      groups. We observed 287 instances of technical skills, of which 27.5% were
      attempted by residents. Thematic analysis identified 14 factors, grouped into
      three categories, which influenced whether residents attempted technical skills
      on real patients. Learner factors included resident initiative, perceived need
      for skill acquisition and competing priorities. Teacher factors consisted of
      competing priorities, interest in teaching, perceived need for residents to
      acquire skills, attributions about learners, assessments of competency, and
      trust. Environmental factors were competition from other learners, judgement that
      the patient was appropriate, buy-in from team members, consent from patient or
      caregivers, and physical environment constraints. CONCLUSIONS: Our findings
      suggest that neither the presence of a learner in a clinical environment nor the
      trust of the supervisor is sufficient to ensure the learner will attempt a
      technical skill. We characterise this phenomenon as representing a pool of
      opportunities to conduct technical skills on live patients that shrinks to a much
      smaller pool of technical skill attempts. Learners, teachers and educators can
      use this knowledge to maximise the number of attempts learners make to perform
      technical skills on real patients.

PMID- 29446157
TI  - Adverse transfusion reactions in patients with liver disease.

PMID- 29446156
TI  - 3D NIR-II Molecular Imaging Distinguishes Targeted Organs with High-Performance
      NIR-II Bioconjugates.
AB  - Greatly reduced scattering in the second near-infrared (NIR-II) region (1000-1700
      nm) opens up many new exciting avenues of bioimaging research, yet NIR-II
      fluorescence imaging is mostly implemented by using nontargeted fluorophores or
      wide-field imaging setups, limiting the signal-to-background ratio and imaging
      penetration depth due to poor specific binding and out-of-focus signals. A newly
      developed high-performance NIR-II bioconjugate enables targeted imaging of a
      specific organ in the living body with high quality. Combined with a home-built
      NIR-II confocal set-up, the enhanced imaging technique allows 900 um-deep 3D
      organ imaging without tissue clearing techniques. Bioconjugation of two hormones
      to nonoverlapping NIR-II fluorophores facilitates two-color imaging of different
      receptors, demonstrating unprecedented multicolor live molecular imaging across
      the NIR-II window. This deep tissue imaging of specific receptors in live animals
      allows development of noninvasive molecular imaging of multifarious models of
      normal and neoplastic organs in vivo, beyond the traditional visible to NIR-I
      range. The developed NIR-II fluorescence microscopy will become a powerful
      imaging technique for deep tissue imaging without any physical sectioning or
      clearing treatment of the tissue.

PMID- 29446158
TI  - A neuroscience perspective of the gut theory of Parkinson's disease.
AB  - Parkinson's disease is caused by complex interactions between environmental
      factors and a genetic predisposition. Environmental factors include exposure to
      pesticides and toxins, heavy metals and accumulation of iron and/or manganese in
      the brain. However, accumulating evidence indicates that gut-brain health and
      function are impaired in Parkinson's disease, often a decade before motor
      symptoms are diagnosed. We present the gut-brain theory of Parkinson's disease
      and summarise the peripheral and central nervous system pathology,
      gastrointestinal symptoms experienced by many Parkinson's patients, the route by
      which gut-brain dysfunction may occur and changes in gut microbiota that are
      associated with disease expression. Finally, we consider future gut-based
      treatments to prevent or slow down the progression of Parkinson's disease and
      explore whether this knowledge may highlight biomarkers to be included in complex
      algorithms in the future to assess a person's risk of developing Parkinson's
      disease.

PMID- 29446159
TI  - Arginine vasopressin differentially modulates GABAergic synaptic transmission
      onto temperature-sensitive and temperature-insensitive neurons in the rat
      preoptic area.
AB  - The preoptic area (POA) of the hypothalamus, containing temperature-sensitive and
      temperature-insensitive neurons, plays a key role in specific thermoregulatory
      responses. Although arginine vasopressin (AVP) has been shown to induce
      hypothermia by increasing the firing activities of warm-sensitive neurons and
      decreasing those of cold-sensitive and temperature-insensitive neurons, the
      effects of AVP on POA GABAergic transmission remain unknown. Herein, inhibitory
      postsynaptic currents (IPSCs) of temperature-sensitive and temperature
      insensitive neurons in POA slices were recorded using whole-cell patch clamp. By
      monitoring changes in GABAergic transmission during AVP treatment, we showed that
      AVP decreased the amplitudes and frequencies of spontaneous IPSCs in mostly warm
      sensitive neurons and in some temperature-insensitive neurons but increased these
      parameters in other temperature-insensitive neurons. The IPSC amplitude was
      reduced for only cold-sensitive neurons. RT-PCR and Western blot analyses further
      confirmed the POA expression of V1a receptors and GABAA receptors, including the
      subunits alpha1, alpha2, alpha3, beta2, beta3 and gamma2. The effects of AVP on
      IPSCs in temperature-sensitive and temperature-insensitive neurons were dependent
      on G proteins and intracellular Ca2+ . AVP-mediated modulation was associated
      with changes in the kinetic parameters (decay time, 10-90% rise time, half
      width). Together, these results suggest that AVP, acting via V1a receptors but
      not V1b receptors, differentially modulates GABAergic synaptic transmission and
      fine-tunes the firing activities of temperature-sensitive and temperature
      insensitive neurons in the rat POA.

PMID- 29446160
TI  - Protection against summer solar lentigo over-pigmentation with a SPF30 daily
      cream.
AB  - BACKGROUND/PURPOSE: The aim of this study was to measure lentigines' pigmentation
      over a long period of time and evaluate if summer over-pigmentation can be
      avoided by the use a SPF30 day skin cream. METHODS: Seventeen healthy female
      volunteers aged 50 and over and presenting lentigines participated in the study
      from spring to summer. Throughout the study, all subjects applied a SPF30 daily
      skin cream to only one hand. Color measurements of the target lesions were
      performed with a chromameter and with a color-calibrated camera. Target lesions
      were also imaged with in vivo reflectance confocal microscopy (RCM). A specific
      procedure for re-registering the images was developed to ensure that the same
      papillae were measured over time. RESULTS: Both color measurement methods,
      chromametry and color-calibrated camera, showed that lentigines treated over time
      with the SPF30 day skin cream were significantly lighter than the non-treated
      lentigines. The RCM images showed a decrease in the papillary contrast for the
      treated lentigines. CONCLUSION: This study shows that this over-pigmentation can
      be avoided using a SPF30 day skin cream. Moreover, we have demonstrated that very
      fine re-registration of the RCM images is possible and ensures a more robust
      analysis.

PMID- 29446161
TI  - Advancements and Challenges in Multidomain Multicargo Delivery Vehicles.
AB  - Reparative and regenerative processes are well-orchestrated temporal and spatial
      events that are governed by multiple cells, molecules, signaling pathways, and
      interactions thereof. Yet again, currently available implantable devices fail
      largely to recapitulate nature's complexity and sophistication in this regard.
      Herein, success stories and challenges in the field of layer-by-layer, composite,
      self-assembly, and core-shell technologies are discussed for the development of
      multidomain/multicargo delivery vehicles.

PMID- 29446162
TI  - Endoscopic ultrasonography-guided transenteric pancreatic duct drainage without
      cautery for obstructive pancreatitis as a result of ampullary carcinoma.

PMID- 29446163
TI  - Do we have enough evidence for recommending therapeutic plasma exchange for
      patients with natalizumab-associated progressive multifocal leukoencephalopathy?

PMID- 29446164
TI  - Dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid in a patient with
      acquired reactive perforating collagenosis.
AB  - Bullous pemphigoid (BP) is a common autoimmune blistering disorder with unknown
      etiology. Recently, increasing numbers of BP cases which developed under the
      medication with dipeptidyl peptidase-4 inhibitors (DPP4i), widely used
      antihyperglycemic drugs, have been reported in published works. Here, we report a
      case of DPP4i (teneligliptin)-associated BP that developed in a 70-year-old
      Japanese man. Interestingly, the patient had acquired reactive perforating
      collagenosis (ARPC), which is also known to be associated with the onset of BP.
      In the present case, clinical, histopathological and immunological findings
      suggested that DPP4i rather than ARPC was associated with the onset of BP.

PMID- 29446166
TI  - Phototherapy in the neonatal intensive care unit - quantity and quality.

PMID- 29446165
TI  - Synthetic Transient Crosslinks Program the Mechanics of Soft, Biopolymer-Based
      Materials.
AB  - Actin networks are adaptive materials enabling dynamic and static functions of
      living cells. A central element for tuning their underlying structural and
      mechanical properties is the ability to reversibly connect, i.e., transiently
      crosslink, filaments within the networks. Natural crosslinkers, however, vary
      across many parameters. Therefore, systematically studying the impact of their
      fundamental properties like size and binding strength is unfeasible since their
      structural parameters cannot be independently tuned. Herein, this problem is
      circumvented by employing a modular strategy to construct purely synthetic actin
      crosslinkers from DNA and peptides. These crosslinkers mimic both intuitive and
      noncanonical mechanical properties of their natural counterparts. By isolating
      binding affinity as the primary control parameter, effects on structural and
      dynamic behaviors of actin networks are characterized. A concentration-dependent
      triphasic behavior arises from both strong and weak crosslinkers due to emergent
      structural polymorphism. Beyond a certain threshold, strong binding leads to a
      nonmonotonic elastic pulse, which is a consequence of self-destruction of the
      mechanical structure of the underlying network. The modular design also
      facilitates an orthogonal regulatory mechanism based on enzymatic cleaving. This
      approach can be used to guide the rational design of further biomimetic
      components for programmable modulation of the properties of biomaterials and
      cells.

PMID- 29446167
TI  - Reply: Prevalence of maternal alloantibodies in a large teaching hospital and
      their impact on outcomes of fetuses/neonates.

PMID- 29446168
TI  - Hospital nurses' lived experiences of intelligent resilience: A phenomenological
      study.
AB  - AIM AND OBJECTIVES: To explore Iranian hospital nurses' lived experiences of
      intelligent resilience. BACKGROUND: Nurses do high levels of emotional work when
      fulfilling patients' and their family members' complex needs. Intelligent
      resilience can alleviate nurses' stress and enhance their endurance. DESIGN: This
      study was based on the Husserlian descriptive phenomenology. METHODS: A purposive
      sample of ten hospital nurses was drawn from hospitals affiliated with Hamadan
      University of Medical Sciences, Hamadan, Iran. In-depth semi-structured
      interviews were held to collect data. The seven-step data analysis approach
      proposed by Colaizzi was used for the data analysis. In this study, the adherence
      to consolidated criteria for reporting qualitative guidelines has been followed.
      RESULTS: The participating hospital nurses' lived experiences of intelligent
      resilience came into four main themes of patience and wisdom, reverence,
      situational self-control and appealing to religiosity. Each of the four main
      themes included two subthemes which were having peace and wise quietness,
      reverence for the patients, physicians and nurses, distancing themselves from
      stressful situations and displacing staff who cause stress, and the nurse's trust
      in God as well as the patient and his family's trust in God, respectively.
      CONCLUSION: Nurses with intelligent resilience are able to bring peace, reverence
      for others and situational self-control to stressors thereby providing higher
      quality of care to their patients. RELEVANCE TO CLINICAL PRACTICE: Nurses work in
      unstable and stressful conditions. The findings of this study provide better
      understanding about the concept of nurses' intelligent resilience and its
      indicators and attributes.

PMID- 29446169
TI  - Oxygen concentration modulates cellular senescence and autophagy in human
      trophoblast cells.
AB  - PROBLEM: We investigated the effect of oxygen concentrations on cellular
      senescence and autophagy and examined the role of autophagy in human trophoblast
      cells. METHOD OF STUDY: Human first-trimester trophoblast cells (Sw.71) were
      incubated under 21%, 5%, or 1% O2 concentrations for 24 hours. We examined the
      extent of senescence caused using senescence-associated beta-galactosidase (SA
      beta-Gal) and senescence-associated secretory phenotype (SASP) as markers.
      Moreover, we examined the role of autophagy in causing cellular senescence using
      an autophagy inhibitor (3-methyladenine, 3MA). RESULTS: Physiological normoxia
      (5% O2 ) decreased SA-beta-Gal-positive cells and SASP including interleukin-6
      (IL-6) and IL-8 compared with cultured cells in 21% O2 . Pathophysiological
      hypoxia (1% O2 ) caused cytotoxicity, including extracellular release of ATP and
      lactate dehydrogenase, and decreased senescence phenotypes. 3MA-treated
      trophoblast cells significantly suppressed senescence markers (SA-beta-Gal
      positive cells and SASP secretion) in O2 -independent manner. CONCLUSION: We
      conclude that O2 concentration modulates cellular senescence phenotypes
      regulating autophagy in the human trophoblast cells. Moreover, inhibiting
      autophagy suppresses cellular senescence, suggesting that autophagy contributes
      to oxygen stress-induced cellular senescence.

PMID- 29446170
TI  - Magnetic resonance elastography of the lumbar back muscles: A preliminary study.
AB  - Back pain is associated with increased lumbar paraspinal muscle (LPM) stiffness
      identified by manual palpation and strain elastography. Recently, magnetic
      resonance elastography (MRE) has allowed the stiffness of muscle to be
      characterized noninvasively in vivo, providing quantitative 3D stiffness maps
      (elastograms). The aim of this study was to characterize the stiffness (shear
      modulus, SM) of the LPM (multifidus and erector spinae) using MRE. MRE of the
      lumbar region was performed on seven adults in supine position. MRE was acquired
      in three muscular states: relaxed with outstretched legs, stretched with passive
      pelvis flexion, and contracted with outstretched legs and tightened trunk
      muscles. The mean SM was measured within a region of interest manually defined in
      the multifidus, erector spinae, and the entire paraspinal compartment. The
      intermuscular difference and the effects of stretching and contraction were
      assessed by ANOVA and t-tests. At rest, the mean SM of the paraspinal compartment
      was 1.6 +/- 0.2 kPa. It increased significantly with stretching to 1.65 +/- 0.3
      kPa, and with contraction to 2.0 +/- 0.7 kPa. Irrespective of muscular state, the
      erector spinae was significantly stiffer than the multifidus. The multifidus
      underwent proportionally higher stiffness changes from rest to contraction and
      stretching. MRE can be used to measure the stiffness of the LPM in different
      muscular states. We hypothesize that, irrespective of posture, the erector spinae
      behaves as semi-rigid beam, and ensures permanent stiffness of the spine. The
      multifidus behaves as an adaptable muscle that provides segmental flexibility to
      the spine and tunes the spine stiffness. Clin. Anat. 31:514-520, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 29446171
TI  - Retrospective Analysis of Intrathecal Drug Delivery: Outcomes, Efficacy, and Risk
      for Cancer-Related Pain at a High Volume Academic Medical Center.
AB  - OBJECTIVES: Cancer pain is common and difficult to treat, as conservative medical
      management fails in approximately 20% of patients for reasons such as intolerable
      side-effects or failure to control pain. Intrathecal drug delivery systems
      (IDDS), while underutilized, can be effective tools to treat intractable cancer
      pain. This study aims to determine the degree of pain relief, efficacy, and
      safety of patients who underwent IDDS implantation at a multidisciplinary pain
      clinic. MATERIALS AND METHODS: A retrospective review was conducted of patients
      with an intrathecal pain pump implanted for malignant pain. Charts were reviewed
      for demographics, cancer type, pain scores before and after implantation, and
      intrathecal drugs utilized. A Wilcoxon Signed-Rank test was conducted on the
      paired differences of pain scores before and after implant. A regression analysis
      was conducted using a linear model to assess effects of demographic variables on
      change in pain scores. RESULTS: 160 patients were included in analysis. The
      median pain score was 7.1 at time of implantation and 5.0 at one-month
      postimplantation. For patients with both baseline and one-month pain scores
      available, the median decrease in pain was 2.5 (p < 0.0001). Pain scores three
      month postimplantation did not significantly differ from one-month
      postimplantation. Median longevity was 65 days. Five patients had pumps explanted
      due to infection with a median time to pump extraction of 28 days. CONCLUSIONS:
      IDDS has the potential to improve cancer pain in a variety of patients and should
      be strongly considered as an option for those with cancer pain intractable to
      conservative medical management.

PMID- 29446172
TI  - Measuring the prevalence of intradialytic hypotension in a satellite dialysis
      clinic: Are we too complacent?
AB  - AIMS AND OBJECTIVES: To measure the prevalence of symptomatic (S-IDH) and
      asymptomatic intradialytic hypotension (A-IDH) or postdialysis overhydration in a
      satellite haemodialysis clinic in Western Australia. BACKGROUND: Intradialytic
      hypotension is one of the most common side effects of haemodialysis caused by
      ultrafiltration provoking a temporary volume depletion. The prevalence of
      asymptomatic hypotension during dialysis has been rarely reported, but is
      considered to have the same negative consequences as symptomatic hypotension on
      various end organs like the brain and the gastrointestinal tract. DESIGN:
      Observational study on a retrospective 3-month period of nursing recorded fluid
      related adverse events. METHODS: Data collection on the occurrence of S-IDH and A
      IDH during a total of 2,357 haemodialysis treatments in 64 patients. Body weight
      of patients at the time of cessation of treatment was recorded, and patients,
      whose weight exceeded their ideal body weight by at least 0.5 kg, were classified
      as overhydrated. Data analysis was performed using spss version 24 software.
      RESULTS: Symptomatic intradialytic hypotension was the most common adverse event
      measured in this cohort, and occurred during 221 (9.4%) of all treatments,
      whereas asymptomatic intradialytic hypotension occurred in 88 (3.7%) of all
      treatments. The total occurrence of intradialytic hypotension was 13.1%, and
      symptomatic was observed in 30 patients, implying that nearly every second
      patient had at least one symptomatic episode within 3 months. Overhydration
      occurred in a total of 103 (4.4%) of all treatments, and involved 17 patients.
      CONCLUSIONS: Symptomatic and asymptomatic intradialytic hypotension were the most
      commonly observed adverse events in this cohort; overhydration occurrence was
      considerably less common. RELEVANCE TO CLINICAL PRACTICE: The high occurrence of
      hypotension-related events demonstrates that ultrafiltration treatment goals in
      satellite dialysis clinics are sometimes overestimated, resulting in regular
      significant symptomatic episodes for the patient. Raising the awareness of the
      prevalence of IDH amongst renal nurses could be an essential initial step before
      collectively preventative strategies in haemodialysis satellite units are
      implemented.

PMID- 29446173
TI  - Surprise: The classic white seedling 3 mutant in maize lacks plastoquinone-9 but
      can still make carotenoids.

PMID- 29446174
TI  - Comorbid depressive symptoms and self-esteem improve after either cognitive
      behavioural therapy or family-based treatment for adolescent bulimia nervosa.
AB  - This study examined the effect of family-based treatment for bulimia nervosa (FBT
      BN) and cognitive behavioral therapy for adolescents (CBT-A) on depressive
      symptoms and self-esteem in adolescents with BN. Data were collected from 110
      adolescents, ages 12-18, who met Diagnostic and Statistical Manual of Mental
      Disorders-Fourth Edition, text revision criteria for BN or partial BN.
      Participants were randomly assigned to FBT-BN or CBT-A and completed measures of
      depressive symptoms and self-esteem before and after treatment and at 6- and 12
      month follow-up assessments. Depressive symptoms and self-esteem significantly
      improved in both treatments, and neither treatment appeared superior on these
      clinical outcomes. Parents often worry whether FBT-BN addresses comorbid
      depressive symptoms and low self-esteem. Our findings address this concern, as
      they demonstrate that FBT-BN does not differ from CBT-A in improving depressive
      symptoms and self-esteem, and both treatments result in symptom improvement.
      These findings can help clinicians guide families to choose a treatment that
      addresses BN and depressive symptoms and low self-esteem.

PMID- 29446175
TI  - Conceptualizing workplace cyberbullying: Toward a definition for research and
      practice in nursing.
AB  - AIMS: To explore nurses' understandings and perceptions of workplace
      cyberbullying, in order to develop a relevant and meaningful definition of the
      phenomenon for future research and practice. BACKGROUND: Although previous
      research places nurses at an elevated risk of exposure to traditional workplace
      bullying, there is a notable absence of research investigating workplace
      cyberbullying within this profession. Considering the detrimental outcomes
      experienced by the targets of workplace cyberbullying, this is an issue that
      warrants focus. METHODS: Utilizing relevant scenarios as prompts, semi-structured
      interviews were conducted with 16 nurses (practising and in training) to explore
      their understanding of the concept and dynamics of workplace cyberbullying.
      RESULTS: Three high-level themes were identified and discussed: (1) cyber
      specific features that make cyberbullying more damaging than traditional
      bullying; (2) the importance of context; and (3) the work environment factors
      that facilitate the occurrence of workplace cyberbullying. CONCLUSIONS: Our
      refined definition facilitates the investigation of a broader and more inclusive
      range of behaviours that targets may experience as workplace cyberbullying, and
      our findings in general highlight potential antecedents in common with
      traditional workplace bullying. IMPLICATIONS FOR NURSING MANAGEMENT: Given the
      work environment and the challenges faced by the nursing profession, a system
      wide approach to intervention and management is recommended, along with utilizing
      a nursing-specific definition.

PMID- 29446176
TI  - Meningococcal conjugate vaccine safety surveillance in the Vaccine Safety
      Datalink using a tree-temporal scan data mining method.
AB  - PURPOSE: The objective of our study was to conduct a data mining analysis to
      identify potential adverse events (AEs) following MENACWY-D using the tree
      temporal scan statistic in the Vaccine Safety Datalink population and demonstrate
      the feasibility of this method in a large distributed safety data setting.
      METHODS: Traditional pharmacovigilance techniques used in vaccine safety are
      generally geared to detecting AEs based on pre-defined sets of conditions or
      diagnoses. Using a newly developed tree-temporal scan statistic data mining
      method, we performed a pilot study to evaluate the safety profile of the
      meningococcal conjugate vaccine Menactra(r) (MenACWY-D), screening thousands of
      potential AE diagnoses and diagnosis groupings. The study cohort included
      enrolled participants in the Vaccine Safety Datalink aged 11 to 18 years who had
      received MenACWY-D vaccination(s) between 2005 and 2014. The tree-temporal scan
      statistic was employed to identify statistical associations (signals) of AEs
      following MENACWY-D at a 0.05 level of significance, adjusted for multiple
      testing. RESULTS: We detected signals for 2 groups of outcomes: diseases of the
      skin and subcutaneous tissue, fever, and urticaria. Both groups are known AEs
      following MENACWY-D vaccination. We also identified a statistical signal for
      pleurisy, but further examination suggested it was likely a false signal. No new
      MENACWY-D safety concerns were raised. CONCLUSIONS: As a pilot study, we
      demonstrated that the tree-temporal scan statistic data mining method can be
      successfully applied to screen broadly for a wide range of vaccine-AE
      associations within a large health care data network.

PMID- 29446177
TI  - How does retirement affect healthcare expenditures? Evidence from a change in the
      retirement age.
AB  - Using individual-level administrative panel data from Hungary, we estimate causal
      effects of retirement on outpatient and inpatient care expenditures and
      pharmaceutical expenditures. Our identification strategy is based on an increase
      in the official early retirement age of women, using that the majority of women
      retire upon reaching that age. According to our descriptive results, people who
      are working before the early retirement age have substantially lower healthcare
      expenditures than nonworkers, but the expenditure gap declines after retirement.
      Our causal estimates from a two-part (hurdle) model show that the shares of women
      with positive outpatient care, inpatient care, and pharmaceutical expenditures,
      respectively, decrease by 3.0, 1.4, and 1.3 percentage points in the short run
      due to retirement. These results are driven by the relatively healthy, by those
      who spent some time on sick leave and by the less educated. The effect of
      retirement on the size of positive healthcare expenditures is generally not
      significant.

PMID- 29446178
TI  - Health-promoting behaviours of Iranian nurses and its relationship with some
      occupational factors: A cross sectional study.
AB  - AIM: To assess the prevalence of health-promoting behaviours (HPBs) and their
      associations with some occupational factors among nurses. BACKGROUND: Health
      promoting behaviours are significant indicators of health status. Nurses' HPBs
      may have a direct impact on patients' care and safety. METHODS: A descriptive,
      questionnaire design was conducted among nursing staff (n = 136) in a district
      hospital in Iran during 2015. Data was collected using a two-part questionnaire,
      which included the Health Promoting Lifestyle Profile II. Data was analysed using
      the Pearson correlation coefficient, and independent t and ANOVA tests (alpha =
      .05). RESULTS: The stress-management and physical activity dimensions had the
      lowest mean score and health responsibility had the highest. The HPBs of nurses
      with rotating/irregular shifts, contract employment, and low income were
      significantly lower. CONCLUSIONS: Nurses' HPBs should be promoted in the stress
      management and physical activity dimensions. In this regard, contract nurses,
      shift nurses, and low-income nurses are the priorities. IMPLICATIONS FOR NURSING
      MANAGEMENT: Nurse managers should give more attention to promote nurses' HPBs
      especially in the areas of stress management and physical activity through
      implementation of healthy lifestyle programs. Nursing policy makers should give
      attention to permanent recruitment and improving salary as a strategy to improve
      nurses' HPBs.

PMID- 29446179
TI  - Genomic diversity of a nectar yeast clusters into metabolically, but not
      geographically, distinct lineages.
AB  - Both dispersal limitation and environmental sorting can affect genetic variation
      in populations, but their contribution remains unclear, particularly in microbes.
      We sought to determine the contribution of geographic distance (as a proxy for
      dispersal limitation) and phenotypic traits (as a proxy for environmental
      sorting), including morphology, metabolic ability and interspecific
      competitiveness, to the genotypic diversity in a nectar yeast species,
      Metschnikowia reukaufii. To measure genotypic diversity, we sequenced the genomes
      of 102 strains of M. reukaufii isolated from the floral nectar of hummingbird
      pollinated shrub, Mimulus aurantiacus, along a 200-km coastline in California.
      Intraspecific genetic variation showed no detectable relationship with geographic
      distance, but could be grouped into three distinct lineages that correlated with
      metabolic ability and interspecific competitiveness. Despite ample evidence for
      strong competitive interactions within and among nectar yeasts, a full spectrum
      of the genotypic and phenotypic diversity observed across the 200-km coastline
      was represented even at a scale as small as 200 m. Further, more competitive
      strains were not necessarily more abundant. These results suggest that dispersal
      limitation and environmental sorting might not fully explain intraspecific
      diversity in this microbe and highlight the need to also consider other
      ecological factors such as trade-offs, source-sink dynamics and niche
      modification.

PMID- 29446180
TI  - Pigs expressing the human inhibitory ligand PD-L1 (CD 274) provide a new source
      of xenogeneic cells and tissues with low immunogenic properties.
AB  - BACKGROUND: The programmed cell death-1 (PD-1, CD279)/PD-Ligand1 (PD-L1, CD274)
      receptor system is crucial for controlling the balance between immune activation
      and induction of tolerance via generation of inhibitory signals. Expression of PD
      L1 is associated with reduced immunogenicity and renders cells and tissues to an
      immune-privileged/tolerogenic state. METHODS: To apply this concept for clinical
      xenotransplantation, we generated human (h)PD-L1 transgenic pigs and
      characterized expression and biological function of the transgene at the cellular
      level. RESULTS: The hPD-L1 was detected in kidney, heart, and pancreas. In
      addition, peripheral blood mononuclear cells (PBMC), cultured fibroblasts, and
      endothelial cells were hPD-L1 positive (hPD-L1+ ). The hPD-L1 levels were
      increased by the treatment of transgenic cells with human cytokines (eg, TNF
      alpha), suggesting a regulatable mode of transgene expression. Compared to cells
      from wild-type pigs, hPD-L1+ PBMC had a significantly reduced capacity to
      stimulate proliferation of human CD4+ T cells. Moreover, fibroblasts from hPD-L1
      transgenic pigs were partially protected from cell-mediated lysis by human
      cytotoxic effector cells. CONCLUSIONS: These data indicate a low immunogenic,
      immune-protected status of cells from hPD-L1 transgenic pigs. The integration of
      the hPD-L1 concept into existing multi-transgenic pigs is promising to achieve
      long-term survival of porcine xenografts in non-human primate recipients.

PMID- 29446181
TI  - 51st Annual Conference of Physiology and Pathology, of Reproduction and 43rd
      Mutual Conference of Veterinary and Human Reproductive Medicine Hannover, 21st -
      23rd of February 2018. 51.

PMID- 29446182
TI  - Catheter ablation of ventricular arrhythmias with QRS morphology resembling that
      of aortic sinus cusp arrhythmias: Significance of mapping the left pulmonary
      sinus cusp.
AB  - BACKGROUND: There is a close anatomical relationship between aortic sinus cusp
      (ASC) and the left pulmonary sinus cusp (LPSC). PURPOSE: The study was to
      investigate the significance of mapping and ablation of LPSC for ventricular
      arrhythmias (VAs) with QRS morphology resembling that of ASC arrhythmias.
      METHODS: In 33 consecutive patients undergoing successful catheter ablation of
      idiopathic VAs with ASC arrhythmia-like QRS morphology, LPSC was mapped
      carefully. RESULTS: Among the 33 patients studied, QRS morphology resembled that
      of arrhythmias of either right or left coronary cusp (LCC or RCC) origin in 17
      and 16 patients, respectively. Out of 12 arrhythmias with the earliest potential
      in LCC during left-sided mapping, an earlier potential in LPSC than in LCC was
      recorded in 2 arrhythmias, the same earliest potential in LPSC as in LCC was
      recorded in 6 arrhythmias, and 5 (42%) were finally ablated successfully in LPSC
      using the reversed U curve. Out of 16 arrhythmias with the earliest potential in
      the RCC during left-sided mapping, an earlier potential in LPSC than in RCC was
      recorded in 4 arrhythmias, the same earliest potential in LPSC as in RCC was
      recorded in 3 arrhythmias, and 4 (25%) were finally ablated successfully in LPSC
      using the reversed U curve. CONCLUSIONS: For VAs with ASC arrhythmia-like QRS
      morphology, mapping in LPSC could have unique electrophysiologic characteristics,
      and some of them could be eliminated in LPSC using reversed U curve.

PMID- 29446183
TI  - Comparison of detergent-based decellularization protocols for the removal of
      antigenic cellular components in porcine aortic valve.
AB  - BACKGROUND: Various detergent-based protocols are used to remove cells and
      cellular debris in porcine aortic valve (PAV). However, the removal of antigenic
      cellular components has not been thoroughly elucidated to date. In this study, we
      used 4 detergent-based protocols to decellularize PAVs and aimed to evaluate
      their effects on removing antigenic cellular components. METHODS: Porcine aortic
      valves were decellularized using sodium dodecyl sulfate (SDS), SDS in combination
      with sodium deoxycholate (SDS/SD), Triton X-100, and Triton X-100 in combination
      with SD (Triton X-100/SD), respectively. Untreated PAVs were used as controls.
      Immunohistochemical and SDS-polyacrylamide gel electrophoresis (SDS-PAGE)
      analyses were performed to determine the removal of antigenic protein components.
      Histological, biochemical, and biomechanical analyses were performed to determine
      the preservation and mechanical properties of the extracellular matrix. PAV
      tissues were implanted subcutaneously in Sprague Dawley rats to evaluate the host
      immune response. Implanted PAVs were taken out at the indicated time points for
      histological and immunohistochemical examinations. RESULTS: All 4 protocols
      effectively removed the membrane antigenic proteins major histocompatibility
      complex I molecule and galactose-alpha-1,3 galactose. The SDS/SD protocol was the
      most effective method to remove the cytoplasmic cytoskeletal proteins, vimentin
      and alpha-SMA, and SDS alone partly removed vimentin protein. The SDS/SD protocol
      was the most effective method to remove nuclear DNA with residual DNA below 50
      ng/mg, followed by the SDS protocol with residual DNA of 74.9 ng/mg. The SDS
      protocol was the most effective method to remove proteins ranged from 10 to 55
      kDa, followed by the SDS/SD protocol. SDS and SDS/SD PAV implants attracted fewer
      neutrophils in vivo on postoperative day 3. The infiltration of macrophages and T
      lymphocytes was significantly lower in SDS and SDS/SD implants on days 14 and day
      28. All of the decellularized protocols that were examined greatly reduced the
      contents of collagen, elastin, and glycosaminoglycan compared to controls.
      Biomechanical analysis revealed significant differences in ultimate tensile
      strength and Young's modulus between control PAVs and decellularized PAVs
      generated using SDS, SDS/SD, Triton X-100, or Triton X-100/SD. CONCLUSIONS: These
      results indicated that SDS-based protocols more effectively removed antigenic
      cellular components compared to Triton X-100-based protocols. These results are
      clinically significant because complete removal of antigenic determinants is
      critical to decrease adverse immune-mediated and inflammatory responses to a PAV
      when used in xenogeneic application.

PMID- 29446184
TI  - Microwave-Assisted, Asymmetric Synthesis of 3-Amino-2,3-Dihydrobenzofuran
      Flavonoid Derivatives from Chalcones.
AB  - A route to access 3-amino-2,3-dihydrobenzofurans that utilizes microwave-assisted
      organic synthesis to rapidly generate analogues has been developed. The route
      begins with an acid-catalyzed, microwave-assisted aldol condensation to generate
      chalcone intermediates, followed by a Corey-Bakshi-Shibata reduction and
      subsequent Sharpless asymmetric epoxidation to access stereoisomeric
      epoxyalcohols. The final step is a one-pot, microwave-assisted, regioselective,
      acid-catalyzed epoxide opening with various amines followed by an intramolecular
      nucleophilic aromatic substitution reaction to generate the 3-amino-2,3
      dihydrobenzofurans. This route provides ready access to stereochemically and
      structurally diverse analogues of these flavonoid scaffolds. Additionally, a
      pilot library was synthesized, and the biological activity diversity of the
      chalcones and dihydrobenzofurans was explored in human carcinoma cell lines.

PMID- 29446185
TI  - Chart validation of inpatient ICD-9-CM administrative diagnosis codes for acute
      myocardial infarction (AMI) among intravenous immune globulin (IGIV) users in the
      Sentinel Distributed Database.
AB  - BACKGROUND: The Sentinel Distributed Database (SDD) is a large database of
      patient-level administrative health care records, primarily derived from
      insurance claims and electronic health records, and is sponsored by the US Food
      and Drug Administration for medical product safety evaluations. Acute myocardial
      infarction (AMI) is a common study endpoint for drug safety studies that rely on
      health records from the SDD and other administrative databases. PURPOSE: In this
      chart validation study, we report on the positive predictive value (PPV) of
      inpatient International Classification of Diseases, Ninth Revision, Clinical
      Modification AMI administrative diagnosis codes (410.x1 and 410.x0) in the SDD.
      METHODS: As part of an assessment of thromboembolic adverse event risk following
      treatment with intravenous immune globulin, charts were obtained for 103
      potential post-intravenous immune globulin AMI cases. Charts were abstracted by
      trained nurses and physician-adjudicated based on prespecified diagnostic
      criteria. RESULTS: Acute myocardial infarction status could be determined for 89
      potential cases. The PPVs for the inpatient AMI diagnoses recorded in the SDD
      were 75% overall (95% CI, 65-84%), 93% (95% CI, 78-99%) for principal-position
      diagnoses, 88% (95% CI, 72-97%) for secondary diagnoses, and 38% (95% CI, 20-59%)
      for position-unspecified diagnoses (eg, diagnoses originating from separate
      physician claims associated with an inpatient stay). Of the confirmed AMI cases,
      demand ischemia was the suspected etiology more often for those coded in
      secondary or unspecified positions (72% and 40%, respectively) than for principal
      position AMI diagnoses (21%). CONCLUSIONS: The PPVs for principal and secondary
      AMI diagnoses were high and similar to estimates from prior chart validation
      studies. Position-unspecified diagnosis codes were less likely to represent true
      AMI cases.

PMID- 29446186
TI  - Longterm persistence and nonrecurrence of depression treatment in Germany: a four
      year retrospective follow-up using linked claims data.
AB  - OBJECTIVES: To measure persistence and nonrecurrence of depression treatment and
      investigate potential risk factors. METHODS: We retrospectively observed a closed
      cohort of insurees with new-onset depression treatment in 2007 and without most
      psychiatric comorbidity for 16 quarters (plus one to ascertain discontinuation).
      We linked inpatient/outpatient/drug-data per person and quarter. Person-quarters
      containing specified depression services were classified as depression-treatment
      person-quarters (DTPQ). We defined longterm-DTPQ-persistence as 16 + 1 continuous
      DTPQ and longterm-DTPQ-nonrecurrence as 12 continuous quarters without DTPQ and
      used multivariate logistic regression to explore associations with these
      outcomes. RESULTS: Within first 16 quarters, 28,348 patients' first period (total
      time) persisted for a mean/median 5.4/3 (8.7/8) quarters. Fourteen percent had
      longterm-DTPQ-persistence, associated (p < .05) with baseline hospital (odds
      ratio, OR = 1.80), psychotherapy/specialist-interview and antidepressants (OR =
      1.81), age (years, OR = 1.03), unemployment (OR = 1.21), retirement (OR = 1.31),
      and insured as a dependent (OR = 1.32). Thirty-four percent had longterm-DTPQ
      nonrecurrence, associated with psychotherapy/specialist-interview (OR = 1.40),
      antidepressants (OR = 0.54), female sex (OR = 0.84), age (years, OR = 0.99),
      retirement (OR = 1.18), and insured as a dependent (OR = 0.88). Women differed
      for episodic and not chronic treatment. CONCLUSION: Treatment measures compared
      to survey's symptoms measures. We suggest further research on "treatment-free
      time." Antidepressants(-) and psychotherapy/specialist-interview(+) were
      significantly associated with longterm-DTPQ-nonrecurrence. This was presumably
      moderated by possible short-time/low-dosage antidepressants use(-) and selective
      therapy assignment(+). Sample selectivity limited data misclassification.

PMID- 29446187
TI  - 4-Fluorophenyl 3-nitro-2-pyridinesulfenate as a practical protecting agent for
      amino acids.
AB  - We report a new protecting agent (1, Npys-OPh(pF)) for 3-nitro-2-pyridine (Npy)
      sulfenylation of amino, hydroxy, and thiol functional groups. Several Npys
      phenoxides were synthesized from Npys chloride (Npys-Cl) and phenols in the
      presence of base in 1-step reaction, and their ability for Npy-sulfenylation was
      evaluated. As a result, 1 was selected as a new Npy-sulfenylation agent with
      advantages including improved physicochemical stability, more controllable
      reactivity, and easier handling than the conventional protecting agent Npys-Cl.

PMID- 29446188
TI  - Synergistic Photoredox Catalysis and Organocatalysis for Inverse Hydroboration of
      Imines.
AB  - The first catalytic inverse hydroboration of imines with N-heterocyclic carbene
      (NHC) boranes has been realized by means of cooperative organocatalysis and
      photocatalysis. This catalytic combination provides a promising platform for
      promoting NHC-boryl radical chemistry under sustainable and radical-initiator
      free conditions. The highly important functional-group compatibility and possible
      application in late-stage hydroborations represent an important step forward to
      an enhanced alpha-amino organoboron library.

PMID- 29446189
TI  - Parents' experiences of neonatal transfer. A meta-study of qualitative research
      2000-2017.
AB  - Transfers of critically ill neonates are frequent phenomena. Even though parents'
      participation is regarded as crucial in neonatal care, a transfer often means
      that parents and neonates are separated. A systematic review of the parents'
      experiences of neonatal transfer is lacking. This paper describes a meta-study
      addressing qualitative research about parents' experiences of neonatal transfer.
      Through deconstruction and reflections of theories, methods, and empirical data,
      the aim was to achieve a deeper understanding of theoretical, empirical,
      contextual, historical, and methodological issues of qualitative studies
      concerning parents' experiences of neonatal transfer over the course of this meta
      study (2000-2017). Meta-theory and meta-method analyses showed that caring,
      transition, and family-centered care were main theoretical frames applied and
      that interviewing with a small number of participants was the preferred data
      collection method. The meta-data-analysis showed that transfer was a scary,
      unfamiliar, and threatening experience for the parents; they were losing familiar
      context, were separated from their neonate, and could feel their parenthood
      disrupted. We identified 'wavering and wandering' as a metaphoric representation
      of the parents' experiences. The findings add knowledge about meta-study as an
      approach for comprehensive qualitative research and point at the value of meta
      theory and meta-method analyses.

PMID- 29446190
TI  - Entropy-Driven Diastereoselectivity Improvement in the Paterno-Buchi Reaction of
      1-Naphthyl Aryl Ethenes with a Chiral Cyanobenzoate through Remote Alkylation.
AB  - The precise stereocontrol of photocycloaddition reactions is still a significant
      challenge owing to their mechanistic complexity and the involvement of highly
      reactive and short-lived intermediates. Attempts have hitherto been made through
      structural modifications, mostly by introducing steric conflicts, to increase the
      difference between the enthalpic barriers. Herein, we show that entropy plays a
      crucial role in influencing the diastereoselectivity of a Paterno-Buchi reaction.
      Remote meta alkylation of the donor caused nominal changes in its photophysical
      properties as well as those of the exciplexes derived thereof. Nevertheless, the
      diastereomeric excess of the oxetane product was greatly improved by about 40 %.
      This enhancement, which is not accompanied by any significant changes in the
      photophysical properties, is difficult to rationalize by conventional enthalpic
      control concepts based on repulsive steric and/or attractive intermolecular
      interactions as well as electronic perturbations. Differential activation
      parameters and compensatory enthalpy-entropy relationships revealed that the
      diastereoselectivity enhancement is not simply enthalpic but also entropic in
      origin.

PMID- 29446191
TI  - Speech understanding in noise in elderly adults: the effect of inhibitory control
      and syntactic complexity.
AB  - BACKGROUND: Previous research has suggested that speech perception in elderly
      adults is influenced not only by age-related hearing loss or presbycusis but also
      by declines in cognitive abilities, by background noise and by the syntactic
      complexity of the message. AIMS: To gain further insight into the influence of
      these cognitive as well as acoustic and linguistic factors on speech perception
      in elderly adults by investigating inhibitory control as a listener
      characteristic and background noise type and syntactic complexity as input
      characteristics. METHODS & PROCEDURES: Phoneme identification was measured in
      different noise conditions and in different linguistic contexts (single words,
      sentences with varying syntactic complexity). Additionally, inhibitory control
      was measured using a visual stimulus-response matching task. Fifty-one adults
      participated in this study, including elderly adults with age-related hearing
      loss (n = 9) and with normal hearing (n = 17), and a control group of normal
      hearing younger adults (n = 25). OUTCOMES & RESULTS: The analysis revealed that
      elderly adults with normal hearing and with hearing loss were less likely to
      identify successfully phonemes in single words than younger normal hearing
      controls. In the context of sentences, only elderly adults with hearing loss had
      a lower odds of correct phoneme perception than the control group. Additionally,
      in elderly adults with hearing loss, phoneme-in-sentence perception was linked to
      age-related declines in inhibitory control. In all participants, phoneme
      identification in sentences was influenced by both noise type and syntactic
      complexity. CONCLUSIONS & IMPLICATIONS: Inhibitory control and syntactic
      complexity might play a significant role in speech perception, especially in
      elderly listeners. These factors might also influence the results of clinical
      assessments of speech perception. Testing procedures thus need to be selected and
      their results interpreted carefully with these influences in mind.

PMID- 29446192
TI  - Increasing the autotrophic growth of Chlorella USTB-01 via the control of
      bacterial contamination by Bdellovibrio USTB-06.
AB  - AIMS: (i) To obtain and identify the predatory bacteria for the control of
      contaminated bacteria and to promote the autotrophic growth of Chlorella USTB-01.
      (ii) To identify and measure the different cell numbers in microalgal culture
      using flow cytometer. METHODS AND RESULTS: A predatory bacterial strain was
      isolated using Escherichia coli BL21 as a sole prey host, which was identified as
      Bdellovibrio USTB-06 by the analysis of 16S rDNA sequence. A flow cytometer was
      successfully used to identify and measure the cell numbers of Chlorella USTB-01,
      the contaminated bacteria and Bdellovibrio USTB-06 simultaneously in the
      autotrophic culture of Chlorella USTB-01 according to the identification of the
      different cell sizes. With the addition of Bdellovibrio USTB-06 at initial 104
      plaque-forming units per ml, the contaminated bacteria severely decreased by
      about five counts (in log10  CFU per ml) and the growth of Chlorella USTB-01 was
      greatly increased by 37.0% compared with those of control respectively.
      CONCLUSIONS: Bdellovibrio USTB-06 could effectively promote the growth of
      Chlorella USTB-01 via the killing of the contaminated bacteria. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Our study reveals a good biotechnology method to increase
      the growth of Chlorella USTB-01 which is very important in the industry of
      microalgal culture.

PMID- 29446193
TI  - Impact of nonintrusive clinical decision support systems on laboratory test
      utilization in a large academic centre.
AB  - BACKGROUND: The near-universal prevalence of electronic health records (EHRs) has
      made the utilization of clinical decision support systems (CDSS) an integral
      strategy for improving the value of laboratory ordering. Few studies have
      examined the effectiveness of nonintrusive CDSS on inpatient laboratory
      utilization in large academic centres. METHODS: Red blood cell folate, hepatitis
      C virus viral loads and genotypes, and type and screens were selected for study.
      We incorporated the appropriate indications for these labs into text that
      accompanied the laboratory orders in our hospital's EHR. Providers could proceed
      with the order without additional clicks. An interrupted time-series analysis was
      performed, and the primary outcome was the rate of tests ordered on all inpatient
      medicine floors. RESULTS: The rate of folate tests ordered per monthly admissions
      showed no significant level change at the time of the intervention with only a
      slight decrease in rate of 0.0109 (P = .07). There was a 43% decrease in the rate
      of hepatitis C virus tests per monthly admissions immediately after the
      intervention with a decrease of 0.0135 tests per monthly admissions (P = .02).
      The rate of type and screens orders per patient days each month had a significant
      downward trend by 0.114 before the intervention (P = .04) but no significant
      level change at the time of the intervention or significant change in rate after
      the intervention. DISCUSSION: Our study suggests that nonintrusive CDSS should be
      evaluated for individual laboratory tests to ensure only effective alerts
      continue to be used so as to avoid increasing EHR fatigue.

PMID- 29446194
TI  - Rhodium-Catalyzed Arylation of Cyclopropenes Based on Asymmetric Direct
      Functionalization of Three-Membered Carbocycles.
AB  - A variety of highly diastereo- and enantiomerically enriched arylcyclopropanes is
      obtained through the asymmetric rhodium-catalyzed arylation reaction of achiral
      nonfunctionalized cyclopropene derivatives with commercially available aryl
      boronic acids in the presence of (R,S)-Josiphos.

PMID- 29446195
TI  - Attachment and therapeutic alliance in psychological therapy for people with
      recent onset psychosis who use cannabis.
AB  - We examine associations between client attachment style and therapeutic alliance
      in a 3-arm randomized controlled trial of brief motivational interviewing and
      cognitive-behavioural therapy compared with longer term motivational interviewing
      and cognitive-behavioural therapy or standard care alone. Client self-report
      measures of attachment style were completed at baseline, and both clients and
      therapists in the treatment arms of the trial completed alliance measures 1 month
      into therapy. We found that insecure-anxious attachment was positively associated
      with therapist-rated alliance, whereas clients with insecure-avoidant attachment
      were more likely to report poorer bond with therapist. There was no evidence that
      client attachment significantly predicted clinical or substance misuse outcomes
      either directly or indirectly via alliance. Nor evidence that the length of
      therapy offered interacted with attachment to predict alliance.

PMID- 29446196
TI  - Laboratory maintenance does not alter ecological and physiological patterns among
      species: a Drosophila case study.
AB  - Large comparative studies in animal ecology, physiology and evolution often use
      animals reared in the laboratory for many generations; however, the relevance of
      these studies hinges on the assumption that laboratory populations are still
      representative for their wild living conspecifics. In this study, we investigate
      whether laboratory-maintained and freshly collected animal populations are
      fundamentally different and whether data from laboratory-maintained animals are
      valid to use in large comparative investigations of ecological and physiological
      patterns. Here, we obtained nine species of Drosophila with paired populations of
      laboratory-maintained and freshly collected flies. These species, representing a
      range of ecotypes, were assayed for four stress-tolerance, two body-size traits
      and six life-history traits. For all of these traits, we observed small
      differences in species-specific comparisons between field and laboratory
      populations; however, these differences were unsystematic and laboratory
      maintenance did not eclipse fundamental species characteristics. To investigate
      whether laboratory maintenance influence the general patterns in comparative
      studies, we correlated stress tolerance and life-history traits with
      environmental traits for the laboratory-maintained and freshly collected
      populations. Based on this analysis, we found that the comparative physiological
      and ecological trait correlations are similar irrespective of provenience. This
      finding is important for comparative biology in general because it validates
      comparative meta-analyses based on laboratory-maintained populations.

PMID- 29446197
TI  - Epithelial-mesenchymal transition and plasticity in the developmental basis of
      cancer and fibrosis.

PMID- 29446199
TI  - Light-Dependent Cytoplasmic Recruitment Enhances the Dynamic Range of a Nuclear
      Import Photoswitch.
AB  - Cellular signal transduction is often regulated at multiple steps to achieve more
      complex logic or precise control of a pathway. For instance, some signaling
      mechanisms couple allosteric activation with localization to achieve high signal
      to noise. Here, we create a system for light-activated nuclear import that
      incorporates two levels of control. It consists of a nuclear import photoswitch,
      light-activated nuclear shuttle (LANS), and a protein engineered to
      preferentially interact with LANS in the dark, Zdk2. First, Zdk2 is tethered to a
      location in the cytoplasm that sequesters LANS in the dark. Second, LANS
      incorporates a nuclear localization signal (NLS) that is sterically blocked from
      binding to the nuclear import machinery in the dark. If activated with light,
      LANS both dissociates from its tethered location and exposes its NLS, which leads
      to nuclear accumulation. We demonstrate that this coupled system improves the
      dynamic range of LANS in mammalian cells, yeast, and Caenorhabditis elegans and
      provides tighter control of transcription factors that have been fused to LANS.

PMID- 29446200
TI  - Stabilizing and Organizing Bi3 Cu4 and Bi7 Cu12 Nanoclusters in Two-Dimensional
      Metal-Organic Networks.
AB  - Multinuclear heterometallic nanoclusters with controllable stoichiometry and
      structure are anticipated to possess promising catalytic, magnetic, and optical
      properties. Heterometallic nanoclusters with precise stoichiometry of Bi3 Cu4 and
      Bi7 Cu12 can be stabilized in the scaffold of two-dimensional metal-organic
      networks on a Cu(111) surface through on-surface metallosupramolecular self
      assembly processes. The atomic structures of the nanoclusters were resolved using
      scanning tunneling microscopy and density functional theory calculations. The
      nanoclusters feature highly symmetric planar hexagonal shapes and core-shell
      charge modulation. The clusters are arranged as triangular lattices with a
      periodicity that can be tuned by choosing molecules of different size. This work
      shows that on-surface metallosupramolecular self-assembly creates unique
      possibilities for the design and synthesis of multinuclear heterometallic
      nanoclusters.

PMID- 29446201
TI  - Transposable elements shape the human proteome landscape via formation of cis
      acting upstream open reading frames.
AB  - Transposons are major drivers of mammalian genome evolution. To obtain new
      insights into the contribution of transposons to the regulation of protein
      translation, we here examined how transposons affected the genesis and function
      of upstream open reading frames (uORFs), which serve as cis-acting elements to
      regulate translation from annotated ORFs (anORFs) located downstream of the uORFs
      in eukaryotic mRNAs. Among 39,786 human uORFs, 3,992 had ATG trinucleotides of a
      transposon origin, termed "transposon-derived upstream ATGs" or TuATGs.
      Luciferase reporter assays suggested that many TuATGs modulate translation from
      anORFs. Comparisons with transposon consensus sequences revealed that most TuATGs
      were generated by nucleotide substitutions in non-ATG trinucleotides of
      integrated transposons. Among these non-ATG trinucleotides, GTG and ACG were
      converted into TuATGs more frequently, indicating a CpG methylation-mediated
      process of TuATG formation. Interestingly, it is likely that this process
      accelerated human-specific upstream ATG formation within transposon sequences in
      5' untranslated regions after divergence between human and nonhuman primates.
      Methylation-mediated TuATG formation seems to be ongoing in the modern human
      population and could alter the expression of disease-related proteins. This study
      shows that transposons have potentially been shaping the human proteome landscape
      via cis-acting uORF creation.

PMID- 29446202
TI  - Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and
      cognitive behaviors.
AB  - Inhibitory interneurons mediate the gating of synaptic transmission and modulate
      the activities of neural circuits. Disruption of the function of inhibitory
      networks in the forebrain is linked to impairment of social and cognitive
      behaviors, but the involvement of inhibitory interneurons in the cerebellum has
      not been assessed. We found that Cadherin 13 (Cdh13), a gene implicated in autism
      spectrum disorder and attention-deficit hyperactivity disorder, is specifically
      expressed in Golgi cells within the cerebellar cortex. To assess the function of
      Cdh13 and utilize the manipulation of Cdh13 expression in Golgi cells as an entry
      point to examine cerebellar-mediated function, we generated mice carrying Cdh13
      floxed alleles and conditionally deleted Cdh13 with GlyT2::Cre mice. Loss of
      Cdh13 results in a decrease in the expression/localization of GAD67 and reduces
      spontaneous inhibitory postsynaptic current (IPSC) in cerebellar Golgi cells
      without disrupting spontaneous excitatory postsynaptic current (EPSC). At the
      behavioral level, loss of Cdh13 in the cerebellum, piriform cortex and
      endopiriform claustrum have no impact on gross motor coordination or general
      locomotor behaviors, but leads to deficits in cognitive and social abilities.
      Mice lacking Cdh13 exhibit reduced cognitive flexibility and loss of preference
      for contact region concomitant with increased reciprocal social interactions.
      Together, our findings show that Cdh13 is critical for inhibitory function of
      Golgi cells, and that GlyT2::Cre-mediated deletion of Cdh13 in non-executive
      centers of the brain, such as the cerebellum, may contribute to cognitive and
      social behavioral deficits linked to neurological disorders.

PMID- 29446203
TI  - Rooming-in for new mother and infant versus separate care for increasing the
      duration of breastfeeding.

PMID- 29446204
TI  - An up to 17-year follow-up retrospective analysis of a minimally invasive,
      flapless approach: 18 945 implants in 7783 patients.
AB  - BACKGROUND: This study investigates gender, age, jaw, implant position, loading
      protocol (immediate vs delayed), smoking, and type of surgery (punch vs flap) as
      influential factors of implant survival in a large patient collective. PURPOSE:
      To evaluate the survival rates of implants in patients using a mucoperiosteal
      punch for flapless implantation in the majority of cases in order to evaluate its
      medical efficacy and safety. MATERIALS AND METHODS: Between 1994 and 2015 all
      patients with complete data treated at the Wienerberg Dental Clinic, Vienna,
      Austria, were included and statistically analyzed in Cox proportional hazard (PH)
      models. As patients with multiple implants were included, a clustering term was
      added to the Cox PH model to respect pooled failures in patients. RESULTS: Of the
      initial 24 282 ANKYLOS/Dentsply implants placed in 8137 patients a total of 7783
      patients with 18 945 implants were finally included. The mean follow-up was 2.8
      +/- 3.2 up to 17.9 years. Cumulative survival rates (CSRs) after 1, 3, 5, and 10
      years were 98.5%, 97.7%, 96.7%, and 93.0%, respectively. Of these, 17 517 (92.5%)
      implants were placed minimally invasive via a flapless approach by use of the ATP
      Punch with comparable survival rates as observed for flap surgery. The Cox PH
      models proved smoking (hazard ratio [HR] = 2.2) and implant position as
      significant factors of implant survival. In the maxilla, canines and third molars
      were identified as low risk sites in comparison to the most frequently implanted
      first premolar site. In the mandible, the central incisor and second premolar
      were identified as high-risk sites, the canine as low risk site in comparison to
      the most frequently placed first molar site. CONCLUSION: The analyzed data
      concludes the safety and medical efficacy of the ATP-Punch. The CSRs using this
      flapless technique are comparable to the classic surgical flap approach.

PMID- 29446205
TI  - Surgeon-led prostate cancer lymph node staging: pathological outcomes stratified
      by robot-assisted dissection templates and patient selection.
AB  - OBJECTIVES: To evaluate the perioperative, pathological, and oncological outcomes
      from surgeon-led pathological staging of pelvic lymph node (LN) metastases at the
      time of robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Over
      the 6-year period of 2006-2012, three distinct pelvic LN dissection (PLND)
      strategies were used in chronological order at a single cancer referral hospital.
      Strategies were characterised by both an omission of PLND (pNx) vs inclusion
      decision threshold, and standard vs extended templates for patients selected for
      PLND. The three cohorts included: (i) omission vs standard template (04/2006
      10/2007), for dominant Gleason score 4-5 or a prostate-specific antigen (PSA)
      level of >10 ng/mL; (ii) omission/standard vs extended template (11/2007
      12/2010), for dominant Gleason score 4-5, PSA level of >10 ng/mL, any single core
      >7 mm, or >3 ipsilateral positive cores; and (iii) extended template with minimal
      exceptions (01/2011-08/2012). Standard outcomes data compared included: Clavien
      Dindo complication rates, LN metrics (yield, percentage positive), and
      biochemical recurrence (BCR). A novel metric comprised 'pNx regret': the rate of
      pNx patients upgraded/upstaged. Exploratory analyses included selection criteria
      for reduced PLND templates, i.e. low-yield subsets. RESULTS: Standard PLND
      yielded 8-10 LNs and a positive-LN yield of 2.2-6.2%. The addition of an extended
      PLND (E-PLND) significantly increased the yield to 14-20 LNs and the positive-LN
      yield to 17.4-18.4% (both P < 0.001). E-PLND had the highest impact on the
      percentage of positive LNs (%pN1) for high-risk disease (9.3 vs 32.8%, P =
      0.002), modest for intermediate risk (4.2 vs 10.9%, P = 0.003), and minimal
      impact on low risk disease (4.1 vs 0%, P = 0.401). The combined strategies of
      setting a very low threshold for E-PLND and sending separate LN packets increased
      the LN yields (18 vs 24, P < 0.001), but did not significantly change the
      observed %pN1 rates by clinical risk group (P = 0.975). Efforts to reduce the
      need for E-PLND included omission by clinical criteria, but resulting in 'pNx
      regret' in 16-19%. A third of patients with unilateral disease and positive LNs
      were found to have contralateral disease. A subset of men with minimal biopsy
      volume Gleason score 4 + 3 had pN1 rates after E-PLND of three of 14 (21%)
      compared to minimal biopsy volume Gleason score 3 + 4 pN1 rates after E-PLND of 0
      of 31. E-PLND takes about twice as long to perform but with no statistically
      significant difference in complications (5.0 vs 6.0%, P = 0.511). The 5-year BCR
      rates were higher for E-PLND, given the selection criteria, but not different for
      overall survival. CONCLUSIONS: The net benefit of E-PLND remains uncertain, and
      therapeutic impact will probably require a randomised trial, given the strong
      selection criteria. E-PLND contributes to oncological staging in a significant
      number of high- and intermediate-risk patients, and should be bilateral.
      Immediate concerns include longer operative times, but no higher complication
      rates.

PMID- 29446206
TI  - Regression equations to estimate the 2-min walk distance in an adult Asian
      population aged 40-75 years.
AB  - BACKGROUND AND OBJECTIVE: There is increased use of the 2-min walk test (2MWT) to
      assess functional exercise capacity. However, the distance achieved during this
      test may be difficult to interpret in the absence of reference values from a
      local population. Regression equations to estimate the 2-min walk distance (2MWD)
      only exist for American and Brazilian populations. The objective of this study
      was to develop regression equations to estimate the 2MWD in Malaysian adults who
      were free from major health problems. METHODS: Eighty-seven adults (43 males;
      mean +/- SD age: 57.1 +/- 9.6 years) performed two 2MWT using a standardized
      protocol. Heart rate (HR) was recorded every 30 s during the test. Stepwise
      multiple regression analysis was performed using age, gender, height, weight and
      change in HR (DeltaHR) as independent variables, and better of the two 2MWD as
      the dependent variable. A second regression equation, without DeltaHR, was
      planned if DeltaHR was retained as one of the predictors of the 2MWD in the first
      equation. RESULTS: The better of the two 2MWD was 200 +/- 34 m. Males walked 33
      +/- 6 m further than females (P < 0.001). The two regression equations were 196 -
      1.1 * age, years + 1.0 * DeltaHR, bpm + 31.2 * gender (R2 = 0.73) and 279 - 1.7 *
      age, years + 35.9 * gender (R2 = 0.47) with females = 0 and males = 1.
      CONCLUSION: The equations derived in this study may facilitate the interpretation
      of the 2MWD in clinical populations in Malaysia, as well as in countries with
      similar cultural backgrounds to Malaysia.

PMID- 29446207
TI  - VEGF mitigates histone-induced pyroptosis in the remote liver injury associated
      with renal allograft ischemia-reperfusion injury in rats.
AB  - Clinical evidence has indicated a possible link between renal injury and remote
      liver injury. We investigated whether extracellular histone mediates remote
      hepatic damage after renal graft ischemia-reperfusion injury, while vascular
      endothelial growth factor (VEGF) is protective against remote hepatic injury. In
      vitro, hepatocyte HepG2 cultures were treated with histone. In vivo, the Brown
      Norway renal graft was stored in 4 degrees C preservation solution for 24 hours
      and then transplanted into a Lewis rat recipient; blood samples and livers from
      recipients were harvested 24 hours after surgery. Prolonged cold ischemia in
      renal grafts enhanced liver injury 24 hours after engraftment. Caspase-1, ASC,
      NLRP3, and AIM2 expressions in hepatocyte, CD68+ -infiltrating macrophages,
      tissue, and serum interleukin-1beta and -18 were greatly elevated, indicating
      that pyroptosis occurred in the liver and resulted in acute liver functional
      impairment. Blocking the caspase-1 pathway decreased the number of necrotic
      hepatocytes. VEGF treatment suppressed the hepatocyte pyroptosis and liver
      function was partially restored. Our data suggested that renal allograft ischemia
      reperfusion injury is likely associated with acute liver damage due to hepatocyte
      pyroptosis induced by histone and such injury may be protected by VEGF
      administration. VEGF, therefore, may serve as a new strategy against other remote
      organ injuries related to renal transplantation.

PMID- 29446209
TI  - Effect of the iChoose Kidney decision aid in improving knowledge about treatment
      options among transplant candidates: A randomized controlled trial.
AB  - We previously developed a mobile- and web-based decision aid (iChoose Kidney)
      that displays individualized risk estimates of survival and mortality, for the
      treatment modalities of dialysis versus kidney transplantation. We examined the
      effect of iChoose Kidney on change in transplant knowledge and access to
      transplant in a randomized controlled trial among patients presenting for
      evaluation in three transplant centers. A total of 470 patients were randomized
      to standard transplantation education (control) or standard education plus
      iChoose Kidney (intervention). Change in transplant knowledge (primary outcome)
      among intervention versus control patients was assessed using nine items in pre-
      and postevaluation surveys. Access to transplant (secondary outcome) was defined
      as a composite of waitlisting, living donor inquiries, or transplantation. Among
      443 patients (n = 226 intervention; n = 216 control), the mean knowledge scores
      were 5.1 +/- 2.1 pre- and 5.8 +/- 1.9 postevaluation. Change in knowledge was
      greater among intervention (1.1 +/- 2.0) versus control (0.4 +/- 1.8) patients (P
      < .0001). Access to transplantation was similar among intervention (n = 168;
      74.3%) versus control patients (n = 153; 70.5%; P = .37). The iChoose Kidney
      decision aid improved patient knowledge at evaluation, but did not impact
      transplant access. Future studies should examine whether combining iChoose Kidney
      with other interventions can increase transplantation. (Clinicaltrials.gov
      NCT02235571).

PMID- 29446208
TI  - Study rationale, design, and pretransplantation alloantibody status: A first
      report of Clinical Trials in Organ Transplantation in Children-04 (CTOTC-04) in
      pediatric heart transplantation.
AB  - Anti-HLA donor-specific antibodies are associated with worse outcomes after organ
      transplantation. Among sensitized pediatric heart candidates, requirement for
      negative donor-specific cytotoxicity crossmatch increases wait times and
      mortality. However, transplantation with positive crossmatch may increase
      posttransplantation morbidity and mortality. We address this clinical challenge
      in a prospective, multicenter, observational cohort study of children listed for
      heart transplantation (Clinical Trials in Organ Transplantation in Children-04
      [CTOTC-04]). Outcomes were compared among sensitized recipients who underwent
      transplantation with positive crossmatch, nonsensitized recipients, and
      sensitized recipients without positive crossmatch. Positive crossmatch recipients
      received antibody removal and augmented immunosuppression, while other recipients
      received standard immunosuppression with corticosteroid avoidance. This first
      CTOTC-04 report summarizes study rationale and design and relates
      pretransplantation sensitization status using solid-phase technology. Risk
      factors for sensitization were explored. Of 317 screened patients, 290 were
      enrolled and 240 underwent transplantation. Core laboratory evaluation
      demonstrated that more than half of patients were anti-HLA sensitized. Greater
      than 80% of sensitized patients had class I (with or without class II) HLA
      antibodies, and one-third of sensitized patients had at least 1 HLA antibody with
      median fluorescence intensity of >=8000. Logistic regression models demonstrated
      male sex, weight, congenital heart disease history, prior allograft, and
      ventricular assist device are independent risk factors for sensitization.

PMID- 29446210
TI  - Lead exposure reduces sperm quality and DNA integrity in mice.
AB  - Toxicity of lead on male reproductive functions has raised wide public concern as
      environmental lead contamination remains common worldwide. Conflicting and
      controversial data are available regarding effects of lead on male fertility.
      More importantly, our knowledge on effects of lead on sperm DNA integrity is
      significantly limited. Thus, further studies should focus on this issue. In the
      current study, adult male mice were exposed to a series of lead acetate
      concentrations in drinking water for six weeks. Following administration, lead
      levels in blood, testicles, and epididymis were measured, and potential changes
      in morphology of testis and epididymis due to lead exposure were identified. We
      also analyzed sperm parameters, including sperm density, viability, motility, and
      morphology, to evaluate quality of sperm collected from epididymis. Especially,
      hypothetical influence of lead on sperm DNA integrity was also evaluated by
      terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling,
      alkaline comet assay, and sperm chromatin structure assay. Lead exposure possibly
      exerted no effect on growth of mice because these animals acquired similar body
      weight gain during the experimental period. However, high lead concentrations
      (0.5% and 1%) in drinking water affected sperm motility and increased percentage
      of spermatozoa with abnormal morphology. In groups treated with 0.25%, 0.5%, and
      1% lead acetate, percentages of sperm cells showing DNA breaks and chromatin
      structure damage significantly increased. Altogether, lead exposure not only
      exhibits adverse effects on sperm physiological parameters, but also impairs DNA
      structure and integrity. These effects may lead to significant decline in male
      fertility.

PMID- 29446198
TI  - Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2
      mutations.
AB  - The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been
      reported in single populations, with the majority of reports focused on White in
      Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2
      (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351
      families with BRCA2 mutations ascertained from 69 centers in 49 countries on six
      continents. This study comprehensively describes the characteristics of the 1,650
      unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations
      identified in the CIMBA database. We observed substantial variation in mutation
      type and frequency by geographical region and race/ethnicity. In addition to
      known founder mutations, mutations of relatively high frequency were identified
      in specific racial/ethnic or geographic groups that may reflect founder mutations
      and which could be used in targeted (panel) first pass genotyping for specific
      populations. Knowledge of the population-specific mutational spectrum in BRCA1
      and BRCA2 could inform efficient strategies for genetic testing and may justify a
      more broad-based oncogenetic testing in some populations.

PMID- 29446211
TI  - The benefit sharing vision of H3Africa.
AB  - One of the central ethical tenets of research in developing countries is the
      sponsor's obligation to benefit host participants and communities. Two known
      models of benefits provision dominate the ethical discourse of research in
      developing countries. The first model, known as the "reasonable availability,"
      endorses the obligation to provide interventions proven to be effective at the
      end of a study. This contrasts with the second model, known as "fair benefits,"
      which endorses other forms of benefits that host communities may deem as fair
      beyond those derived directly from the study's findings. This paper explores a
      third benefit model consistent with the writings of the Human Hereditary and
      Health in Africa (H3Africa) research initiative. The H3Africa-a North-South
      collaborative initiative predicated by U.S. National Institutes of Health, the
      Wellcome Trust and the African Society of Human Genetics upholds a benefit model
      that endorses capacity building as the primary obligation of its research agenda.
      This is evident by the endorsement of mechanisms to strengthen capacity building
      in its research projects. While capacity building remains a plausible means of
      improving the expertise, quality and independence of research in Africa,
      sustainable measures are needed to realizing the full potential for African-led
      research on the continent.

PMID- 29446212
TI  - Free dialysis in Nepal: Logistical challenges explored.
AB  - Nepal's Ministry of Health began offering free lifetime hemodialysis (HD) in
      2016. There has been a large growth in renal replacement therapy (RRT) services
      offered in Nepal since 2010, when the last known data on the subject was
      published. In 2016, 42 HD centers existed (223% increase since 2010) serving 1975
      end stage renal disease patients (303% increase since 2010); 36 nephrologists
      were registered (200% increase since 2010), 12 were trained in transplantation,
      and 790 transplants had been performed to date. We estimate the incidence of end
      stage renal disease to be 2900 patients (100 per million population). With an
      annual cost of approximately US$2300 per dialysis patient, offering free dialysis
      could potentially cost the government US$6.7 million per year, suggesting that
      2.1% of the annual health budget would be allocated to 0.01% of the population.
      The geographic zone surrounding the capital city, Kathmandu, contains 50% of HD
      centers, but only 14.5% of Nepal's population. Forty-eight percent of the
      population lives within zones without HD service, therefore infrastructure
      challenges exist in providing equitable access to RRT. The aim of this article is
      to summarize the current statistics of RRT in Nepal.

PMID- 29446213
TI  - Osteopontin is essential for IL-1beta production and apoptosis in peri
      implantitis.
AB  - BACKGROUND AND PURPOSE: Peri-implantitis is caused by a cascade of host and
      microbial factors leading to an oral inflammatory disease. The inflammation
      proliferates into supporting tissues surrounding implants and may finally lead to
      a complete loss of osseointegration. Being a phosphorylated glycoprotein secreted
      by immunocompetent cells, osteopontin (OPN) is involved in the differentiation of
      odontoblast-like cells during pulpal healing following tooth transplantation and
      the secretion of type I collagen in reparative dentin. But the production and
      function of OPN in peri-implantitis has not been thoroughly evaluated. MATERIALS
      AND METHODS: Peri-implant crevicular fluid (PICF) was collected from 28 healthy
      implants patients and 28 peri-implantitis patients to determine the expression of
      OPN in response to the inflammation of peri-implantitis by Western-blot, Enzyme
      linked immunosorbent assay (ELISA), and immunofluorescence staining. THP-1
      macrophages infected by Porphyromonas gingivalis were chosen to reveal the
      production and function of OPN in peri-implantitis by immunofluorescence
      staining, quantitative polymerase chain reaction (RT-PCR), and Western-blot.
      RESULTS: Results showed that OPN increased in most PICF of peri-implantitis
      patients and in THP-1 macrophages stimulated with P. gingivalis. The expression
      of OPN in response to P. gingivalis decreased at mRNA and protein levels when
      exposed to either the lectin-type oxidized LDL receptor 1 (LOX-1) neutralizing
      antibody or inhibitor pretreatment in THP-1 macrophages. P. gingivalis induces
      OPN through the Erk1/2 MAPK dependent pathway. OPN neutralization decreased
      interleukin 1 beta (IL-1beta) expression on P. gingivalis infection, and the
      lower IL-1beta mRNA and protein levels were rescued by human osteopontin
      recombinant protein (rhOPN) in THP-1 macrophages. RhOPN suppressed P. gingivalis
      induced apoptosis of the mitochondrial pathway in THP-1 macrophage. CONCLUSIONS:
      Overall, the results of this study provide insight into the essential roles of
      OPN for IL-1beta production and apoptosis in peri-implantitis, as supported by
      the evidence from the study of patient's PICF and cell culture experiments.

PMID- 29446214
TI  - New developments in India concerning the policy of passive euthanasia.
AB  - Euthanasia and assisted dying are illegal in India according to Sections 306 and
      309 of the Indian Penal Code (IPC), and Article 21 of the Constitution of India.
      There have been a number of cases where the Indian High Courts and Indian Supreme
      Court issued differing verdicts concerning the right to life and the right to
      die. Nevertheless, on 7 March 2011, a paradigm shift happened as a result of the
      Indian Supreme Court's judgment on involuntary passive euthanasia in the case of
      Aruna Shanbaug. In its judgment, the Supreme Court requested the government to
      prepare a law on euthanasia. Accordingly, the 241st Report of the Law Commission
      of India proposed a bill to permit passive euthanasia. In May 2016 the Ministry
      of Health and Family Welfare (MOHFW) issued the draft bill for public comment in
      order to create an informed decision. The Indian people are divided on the issue
      of euthanasia. The majority of the scientific community welcome it, while some
      religious groups oppose it. Hindus, in general, express both supporting and
      opposing views on euthanasia, whereas, Christians and Muslims have hardened their
      opposition against it. The Supreme Court judgment and the Report of the Law
      Commission pave the way for the development of new policies pertaining to passive
      euthanasia by the central government of India. Once such legislation is passed,
      passive euthanasia may, and probably will, have an enormous impact on the
      cultural, political, public and medical spheres of India in the near future.

PMID- 29446215
TI  - Elevated success of multispecies bacterial invasions impacts community
      composition during ecological succession.
AB  - Successful microbial invasions are determined by a species' ability to occupy a
      niche in the new habitat whilst resisting competitive exclusion by the resident
      community. Despite the recognised importance of biotic factors in determining the
      invasiveness of microbial communities, the success and impact of multiple
      concurrent invaders on the resident community has not been examined. Simultaneous
      invasions might have synergistic effects, for example if resident species need to
      exhibit divergent phenotypes to compete with the invasive populations. We used
      three phylogenetically diverse bacterial species to invade two compositionally
      distinct communities in a controlled, naturalised in vitro system. By initiating
      the invader introductions at different stages of succession, we could disentangle
      the relative importance of resident community structure, invader diversity and
      time pre-invasion. Our results indicate that multiple invaders increase overall
      invasion success, but do not alter the successional trajectory of the whole
      community.

PMID- 29446216
TI  - Bipolar II should only exist if we can actually study treatments of it.
      Otherwise, what purpose does it serve?

PMID- 29446217
TI  - Clinical staging model in offspring of parents with bipolar disorder: a
      systematic review.
AB  - OBJECTIVE: We sought to systematically review the literature on the psychiatric
      risk of offspring of parents with bipolar disorder (OPBD) using a developmental
      psychopathology framework. The review also sought to establish the utility of
      clinical stage modelling as a framework for identifying precursor disorders to
      later onset of bipolar disorder (BD) in OPBD. METHODS: A systematic search was
      performed using EMBASE, PsychINFO and Medline. Reference lists of included
      studies and previous reviews were also searched. Studies were included if they
      reported diagnostic outcomes for child, adolescent and young adult offspring of
      parents diagnosed with BD. RESULTS: Twenty-six studies were identified
      representing 21 individual cohorts. The review identified that OBPD present as a
      high-risk group for a range of mood and non-mood disorders in childhood,
      adolescence and young adulthood. The trajectory of risk was from non-mood
      disorders in childhood via non-bipolar mood disorders in early adolescence
      towards mania/hypomania in late adolescence and early adulthood. From a clinical
      staging perspective, childhood anxiety disorders were associated with later onset
      of BD. Recurrent substance use disorder was identified as a risk in OPBD during
      late adolescence and early adulthood. Quality ratings indicated that studies were
      methodologically robust. CONCLUSIONS: Our review provides evidence for a
      developmental psychopathology trajectory of precursor risks to BD in OPBD. There
      is support for clinical stage modelling as a conceptual framework for
      understanding developmental risk in OPBD and as a tool for developing early and
      individualized intervention strategies.

PMID- 29446218
TI  - Influence of grandparents on the dietary intake of their 2-12-year-old
      grandchildren: A systematic review.
AB  - AIM: Grandparents are assuming increased child-caregiving responsibilities, which
      potentially influences the dietary intake of grandchildren. The aim of this
      systematic review is to determine the influence of grandparental care on the
      dietary intake, food-related behaviours, food choices and weight status of their
      preschool and school-aged grandchildren. METHODS: Six electronic health databases
      were searched in January 2017. Inclusion criteria were publication in English
      language, peer-reviewed journal between 2000 and 2017; children aged 2-12 years;
      study outcomes included child dietary intake/weight status, grandparent nutrition
      knowledge/beliefs or grandparent/parent feeding practices. Included studies were
      appraised for quality and bias. The review was registered with PROSPERO, number
      CRD42016047518. RESULTS: Sixteen studies were identified in the review, published
      between 2007 and 2016, with 15 assessed as moderate or high quality. Nine studies
      reported grandparental child feeding attitudes and behaviours that are considered
      to negatively influence child dietary intake, while three studies identified
      positive influences. Seven studies identified that differences in child feeding
      attitudes and behaviours between parents and grandparents created conflict and
      tensions between caregivers, often resulting in poor feeding practices.
      Statistically significant positive associations (odds ratio 1.47-1.72) between
      grandparent cohabitation and increased rates of child overweight and obesity were
      found in four studies. CONCLUSIONS: Grandparents in caregiving roles may
      negatively influence the dietary intake and weight status of their grandchildren.
      More rigorous, targeted studies are required to further define the mechanisms by
      which grandparents' knowledge, attitudes and feeding behaviours may influence
      child dietary intake. This review suggests that grandparents may be an important
      audience to target in future child nutrition interventions.

PMID- 29446219
TI  - Hypertension in a resource-limited setting: Is it associated with end organ
      damage in older adults in rural Tanzania?
AB  - Few data from sub-Saharan Africa exist on the effects of hypertension on the
      organs of the human body. We aimed to establish the prevalence of hypertensive
      end organ damage (EOD) in an elderly cohort of Tanzanians. The population aged 70
      years and over of 2 villages in northern Tanzania (n = 246), had blood pressure
      (BP) data available from 2010 and 2013, and underwent in-depth follow-up for
      markers of hypertensive EOD in 2016. Assessment included ankle-brachial pressure
      index, lying-standing BP, electrocardiogram, and mid-stream urine dip. Sustained
      hypertension (those with hypertension at all 3 assessments) was found in 129
      (52.4% subjects). Of the entire cohort, 13.9% had left ventricular hypertrophy
      and 26.4% had peripheral arterial disease, both of which were associated with
      sustained hypertension, although orthostatic hypotension, stroke, proteinuria,
      and arterial stiffening were not. Further investigation, particularly in younger
      age groups, is merited if hypertension-associated morbidity is to be controlled.

PMID- 29446220
TI  - Density-dependent survival varies with species life-history strategy in a
      tropical forest.
AB  - Species coexistence in diverse communities likely results from multiple
      interacting factors. Mechanisms such as conspecific negative density dependence
      (CNDD) and varying life-history strategies related to resource partitioning are
      known to influence plant fitness, and thereby community composition and
      diversity. However, we have little understanding of how these mechanisms interact
      and how they vary across life stages. Here, we document the interaction between
      CNDD and life-history strategy, based on growth-mortality trade-offs, from
      seedling to adult tree for 47 species in a tropical forest. Species' life-history
      strategies remained consistent across stages: fast-growing species had higher
      mortality than slow-growing species at all stages. In contrast, mean CNDD was
      strongest at early life stages (i.e. seedling, sapling). Fast-growing species
      tended to suffer greater CNDD than slow-growing species at several, but not all
      life stages. Overall, our results demonstrate that coexistence mechanisms
      interact across multiple life stages to shape diverse tree communities.

PMID- 29446221
TI  - Stereodivergent Evolution of Artificial Enzymes for the Michael Reaction.
AB  - Enzymes are valuable biocatalysts for asymmetric synthesis due to their exacting
      stereocontrol. Changing the selectivity of an existing catalyst for new
      applications is, however, challenging. Here we show that, in contrast, the
      stereoselectivity of an artificial enzyme created by design and directed
      evolution is readily tunable. We engineered a promiscuous artificial retro
      aldolase into four stereocomplementary catalysts for the Michael addition of a
      tertiary carbanion to an unsaturated ketone. Notably, this selectivity is also
      preserved with alternative Michael nucleophiles. Complete stereodiversification
      of other designer enzymes should similarly be possible by extension of these
      approaches.

PMID- 29446222
TI  - Engineering controls in veterinary oncology: A survey of 148 ACVIM board
      certified oncologists and environmental surveillance in 20 specialty hospitals.
AB  - Engineering controls (EC, facility and equipment barriers between hazards and
      people) are used to avoid exposure to chemotherapy drugs. In this study, American
      College of Veterinary Internal Medicine board-certified veterinary oncologists
      were surveyed about their use of containment primary EC (C-PEC) and supplemental
      EC (closed system transfer devices, CSTD). The survey was completed by 148 (38%)
      of practicing diplomates. All used EC. Both C-PEC and CSTD were used at 92% of
      hospitals; however, US Pharmacopoeial Convention Chapter <800> (USP <800>)
      standards were met at only 19% of hospitals and oncologists did not know the type
      of C-PEC at 18% of hospitals. Next, surface contamination and EC use were
      assessed with environmental surveillance for carboplatin, cyclophosphamide,
      doxorubicin, and vincristine in 20 veterinary specialty hospitals using a
      commercially available kit. No contamination with carboplatin, doxorubicin, or
      vincristine was detected, however, there was contamination with cyclophosphamide
      at 4 hospitals. Based on this study, most veterinary oncologists use C-PEC and
      CSTD, but few meet USP <800> standards. Current measures appear effective for
      preventing contamination with IV drugs, but additional measures are needed for
      oral drugs.

PMID- 29446223
TI  - Evolution and development of scyphozoan jellyfish.
AB  - Scyphozoan jellyfish, or scyphomedusae, are conspicuous members of many ocean
      ecosystems, and have large impacts on human health and industry. Most
      scyphomedusae are the final stage in a complex life cycle that also includes two
      intermediate stages: the larval planula and benthic polyp. In species with all
      three life-cycle stages, the metamorphosis of a polyp into a juvenile
      scyphomedusa (ephyra) is termed strobilation, and polyps can produce one ephyra
      (termed monodisc strobilation) or many ephyrae (termed polydisc strobilation). In
      contrast to species with planula, polyp and medusa stages, a handful of
      scyphozoan species possess modified life cycles with reduced or absent stages.
      The evolutionary patterns associated with strobilation and life-cycle type have
      not been thoroughly investigated, and many studies of ephyra development and
      strobilation induction are not yet synthesized. Herein, I place the development
      of scyphomedusae in an evolutionary context. I first review the current
      evolutionary hypotheses for Scyphozoa. Next, I review what is known about
      scyphomedusa development across a broad diversity of species, including the first
      signs of strobilation, the formation of strobila segments, and the morphogenesis
      of ephyrae. I then review cases where the canonical scyphozoan life cycle has
      been modified, and take advantage of phylogenetic hypotheses to place these
      observations in an evolutionary context. I show that the evolution of monodisc
      strobilation occurred at least twice, and that the loss of intermediate life
      cycle stages occurred several times independently; by contrast, the reduction of
      the medusa stage appears to have occurred within a single clade. I then briefly
      review the major natural cues of strobilation induction. Finally, I summarize
      what is currently known about the molecular mechanisms of strobilation induction
      and ephyra development. I conclude with suggestions for future directions in the
      field.

PMID- 29446224
TI  - Comparative effects of small intestinal glucose on blood pressure, heart rate,
      and noradrenaline responses in obese and healthy subjects.
AB  - Meal consumption leads to an increase in sympathetic output to compensate for
      hemodynamic changes and maintain blood pressure (BP). Obesity is associated with
      a blunting of the sympathetic response to meal ingestion, but interpretation of
      studies investigating these responses is compromised by their failure to account
      for the rate of gastric emptying, which is an important determinant of
      postprandial cardiovascular and sympathetic responses and, in both health and
      obesity, exhibits a wide interindividual variation. We sought to determine the
      effects of intraduodenal glucose infusion, bypassing gastric emptying, on BP,
      heart rate (HR), and noradrenaline responses in obese and healthy control
      subjects. 12 obese subjects (age 36.6 +/- 3.9 years, body mass index (BMI) 36.1
      +/- 1.3 kg/m2 ) and 23 controls (age 27.8 +/- 2.4 years, BMI 22.4 +/- 0.5 kg/m2 )
      received intraduodenal infusions of glucose at 1 or 3 kcal/min, or saline, for 60
      min (t = 0-60 min), followed by intraduodenal saline (t = 60-120 min). BP and HR
      were measured with an automatic cuff, and blood samples collected for measurement
      of plasma noradrenaline. Intraduodenal glucose at 1 kcal/min was associated with
      a fall in diastolic BP in the control subjects only (P < 0.01), with no change in
      systolic BP, HR or noradrenaline in either group. In both groups, intraduodenal
      glucose at 3 kcal/min was associated with a fall in diastolic (P < 0.01), but not
      systolic, BP, and rises in HR (P < 0.001) and plasma noradrenaline (P < 0.01),
      with no difference in responses between the groups. We conclude that
      cardiovascular and sympathetic responses to intraduodenal glucose infusion are
      comparable between obese and control subjects, and dependent on the rate of
      glucose delivery.

PMID- 29446225
TI  - Impact of ureteral stricture and treatment choice on long-term graft survival in
      kidney transplantation.
AB  - We aimed to evaluate the influence of urological complications occurring within
      the first year after kidney transplantation on long-term patient and graft
      outcomes, and sought to examine the impact of the management approach of ureteral
      strictures on long-term graft function. We collected data on urological
      complications occurring within the first year posttransplant. Graft survivals,
      patient survival, and rejection rates were compared between recipients with and
      without urological complications. Male gender of the recipient, delayed graft
      function, and donor age were found to be significant risk factors for urological
      complications after kidney transplantation (P < .05). Death censored graft
      survival analysis showed that only ureteral strictures had a negative impact on
      long-term graft survival (P = .0009) compared to other complications. Death
      censored graft survival was significantly shorter in kidney recipients managed
      initially with minimally invasive approach when compared to the recipients with
      no stricture (P = .001). However, graft survival was not statistically different
      in patients managed initially with open surgery (P = .47). Ureteral strictures
      following kidney transplantation appear to be strongly negatively correlated with
      long-term graft survival. Our analysis suggests that kidney recipients with
      ureteral stricture should be managed initially with open surgery, with better
      long-term graft survival.

PMID- 29446226
TI  - Towards donor lung recovery-gene expression changes during ex vivo lung perfusion
      of human lungs.
AB  - We and others have demonstrated that acellular normothermic ex vivo lung
      perfusion of high-risk donor lungs can result in posttransplant outcomes
      equivalent to that of contemporaneous lung transplantation using standard donor
      lungs. However, the mechanism of this effect remains unclear. Given the
      restoration of cellular metabolic activity during normothermic perfusion, one
      possibility is that of lung healing via natural innate recovery mechanisms. We
      explored this by examining the gene expression changes occurring in human lungs
      during ex vivo lung perfusion. Human lungs clinically rejected for
      transplantation were perfused for 12 hours of EVLP with biopsies taken at the
      start, at 1 hour, at 3 hours, and then every 3 hours thereafter to 12 hours.
      Temporal changes were identified in 2585 genes using the Short Time-series
      Expression Miner and used for pathway analysis. Despite increases in endothelial
      markers of inflammation, circulating leukocyte cell-specific gene expression fell
      over 12 hours of ex vivo lung perfusion (EVLP), suggesting an interrupted
      inflammation response secondary to washout of circulating leukocytes. Analysis of
      these gene changes suggests lung recovery follows specific stages: cellular
      death, cellular preservation, cellular reorganization, and cellular invasion.
      EVLP may improve posttransplant lung function by washout of leukocytes and
      facilitating innate mechanisms of repair.

PMID- 29446227
TI  - Application of nanoperlite as a new natural sorbent in the preconcentration of
      three organophosphorus pesticides by microextraction in packed syringe coupled
      with gas chromatography and mass spectrometry.
AB  - A rapid, low-cost, and simple method is proposed based on a miniaturized solid
      phase extraction named microextraction in packed syringe coupled with gas
      chromatography and mass spectrometry for the preconcentration and determination
      of some organophosphorous pesticides including diazinon, ethion, and malathion.
      For the first time, natural nanoperlite is used as a safe sorbent. Based on this
      technique, the analytes are adsorbed on the solid phase and then eluted by a
      desorbing solvent. The influence of some important parameters such as the
      solution pH, type, and volume of the organic desorption solvent on the
      microextraction efficiency of the selected pesticide technique is investigated.
      The proposed method showed a good linearity in the range of 1.0-35.0 MUg/L for
      ethion and 0.4-30.0 MUg/L for both diazinon and malathion. The limits of
      detection in the range of 0.1-0.38 MUg/L were obtained using the selected ion
      monitoring mode of the mass spectrometer. The reproducibility of the method was
      found to be in the range of 2.8-8.9% for the studied pesticides. To evaluate the
      matrix effect, the developed method is also applied to the preconcentration and
      determination of the selected pesticides in real water samples.

PMID- 29446229
TI  - Biogeographical distribution of bacterial communities in Changbai Mountain,
      Northeast China.
AB  - The broad-leaved and Korean pine mixed forest in Changbai Mountain, China is an
      important component of boreal forest; the area is sensitive to global climate
      change. To understand spatial distribution patterns of soil bacterial community
      along elevation, we analyzed the soil bacterial community diversity and
      composition along an elevational gradient of 699-1177 m in a primitive Korean
      pine forest in Changbai Mountain using the high-throughput sequencing. In total,
      149,519 optimized sequences were obtained. Bacterial Shannon index increased
      along elevation from 699 m to 937 m and started to decrease at the elevation of
      1,044 m, showing a humpback curve along elevation. Evenness (ACE index) and
      richness (Chao index) of the soil bacterial community both decreased with
      elevation (the highest values of 770 and 762 at 699 m and the lowest values of
      548 and 539 at 1,177 m, respectively), all the indices are significantly
      different between elevations. Bacterial composition at phylum and genus levels
      had some differences between elevations, but the dominant bacterial populations
      were generally consistent. Beta-diversity analysis showed a distance-decay
      pattern of bacterial community similarity at different samples. Soil physical and
      chemical properties explained 70.78% of the variation in bacterial community
      structure (soil pH explained 19.95%), and elevational distance only explained
      8.42%. In conclusion, the contemporary environmental disturbances are the
      critical factors in maintaining the bacterial spatial distribution compared with
      historical contingencies.

PMID- 29446230
TI  - Tentative novel lyssavirus in a bat in Finland.
AB  - A tentative novel member of the genus Lyssavirus, designated as Kotalahti bat
      lyssavirus, was detected in a Brandt's bat (Myotis brandtii) in Finland. Based on
      phylogenetic analysis, the virus differs from other known lyssaviruses, being
      closely related to Khujand virus, Aravan virus, Bokeloh bat lyssavirus and
      European bat lyssavirus 2.

PMID- 29446231
TI  - Estimating the burden of influenza-associated hospitalizations and deaths in
      Chile during 2012-2014.
AB  - BACKGROUND: Influenza is a vaccine preventable disease that causes important
      morbidity and mortality worldwide. Estimating the burden of influenza disease is
      difficult. However, there are some methods based in surveillance data and
      laboratory testing that can be used for this purpose. OBJECTIVES: Estimating the
      burden of serious illness from influenza by means of hospitalization and death
      records during the period between 2012 and 2014, and using information from
      Severe Acute Respiratory Illness (SARI) surveillance. METHODS: To estimate the
      Chilean rate of influenza-associated hospitalizations and deaths, we applied the
      influenza positivity of respiratory samples tested in six SARI surveillance
      sentinel hospitals to the hospitalizations and deaths from the records with ICD
      10 codes from influenza and pneumonia. RESULTS: Annually, 5320 people are
      hospitalized for influenza and 447 die for this cause. The annual influenza
      associated hospitalization rate for the period was 71.5/100 000 person-year for
      <5 years old, 11.8/100 000 person-year for people between 5 and 64 years old; and
      156.0/100 000 person-year for >=65 years. The annual mortality rate for the
      period was 0.08/100 000 person-year for <5 years; 0.3/100 000 person-year for
      people between 5 and 64 years; and 22.8/100 000 person-year for >=65 years.
      CONCLUSIONS: This is the first study of influenza burden in Chile. Every year an
      important quantity of hospitalizations and deaths result from influenza
      infection. In countries in temperate zones, it is important to know the burden of
      influenza in order to prepare the health care network and to assess preventive
      intervention currently in practice and the new ones to implementing.

PMID- 29446232
TI  - Bmal1 knockdown suppresses wake and increases immobility without altering orexin
      A, corticotrophin-releasing hormone, or glutamate decarboxylase.
AB  - OBJECTIVE: To determine the effect of Bmal1 knockdown (KD) on sleep, activity,
      immobility, hypothalamic levels of orexin, corticotrophin-releasing hormone
      (CRH), and GABAergic glutamate decarboxylase (GAD). METHODS: We used Bmal1 siRNA,
      or control siRNA intracerebroventricular (ICV) injection to knock down Bmal1 in
      C57BL/6 mice. Sleep polysomnography, wheel-running activity, and tail suspension
      test were performed. Polysomnographic (PSG) recordings in both groups were
      preceded by ICV injection made during both the light phase and the dark phase. We
      also measured brain orexin A and CRH using an ELISA and measured GAD using
      immunoblotting. RESULTS: Compared with control group, Bmal1 KD group had reduced
      wheel activity and increased immobility. Compared with control, the Bmal1 KD
      group had reduced wheel activity and increased immobility. During the first 24
      hours after treatment, we observed that control siRNA induced a much greater
      increase in sleep during the dark phase, which was associated with lower orexin
      levels. However, beginning 24 hours after treatment, we observed an increase in
      sleep and a decrease in time spent awake during the dark phase in the Bmal1 KD
      group. These changes were not associated with changes in brain levels of orexin
      A, CRH, or GAD. CONCLUSION: Bmal1 KD led to reduced activity, increased
      immobility, and dramatic reduction in time spent awake as well as an increase in
      sleep during the dark phase. Early after injection, there was a slight change in
      sleep but brain levels of orexin, CRH, and GAD remain unchanged. Control siRNA
      also affected sleep associated with changes in orexin levels.

PMID- 29446233
TI  - Annual estimates of the burden of seasonal influenza in the United States: A tool
      for strengthening influenza surveillance and preparedness.
AB  - BACKGROUND: Estimates of influenza disease burden are broadly useful for public
      health, helping national and local authorities monitor epidemiologic trends, plan
      and allocate resources, and promote influenza vaccination. Historically,
      estimates of the burden of seasonal influenza in the United States, focused
      mainly on influenza-related mortality and hospitalization, were generated every
      few years. Since the 2010-2011 influenza season, annual US influenza burden
      estimates have been generated and expanded to include estimates of influenza
      related outpatient medical visits and symptomatic illness in the community.
      METHODS: We used routinely collected surveillance data, outbreak field
      investigations, and proportions of people seeking health care from survey results
      to estimate the number of illnesses, medical visits, hospitalizations, and deaths
      due to influenza during six influenza seasons (2010-2011 through 2015-2016).
      RESULTS: We estimate that the number of influenza-related illnesses that have
      occurred during influenza season has ranged from 9.2 million to 35.6 million,
      including 140 000 to 710 000 influenza-related hospitalizations. DISCUSSION:
      These annual efforts have strengthened public health communications products and
      supported timely assessment of the impact of vaccination through estimates of
      illness and hospitalizations averted. Additionally, annual estimates of influenza
      burden have highlighted areas where disease surveillance needs improvement to
      better support public health decision making for seasonal influenza epidemics as
      well as future pandemics.

PMID- 29446228
TI  - Integrins promote axonal regeneration after injury of the nervous system.
AB  - Integrins are cell surface receptors that form the link between extracellular
      matrix molecules of the cell environment and internal cell signalling and the
      cytoskeleton. They are involved in several processes, e.g. adhesion and migration
      during development and repair. This review focuses on the role of integrins in
      axonal regeneration. Integrins participate in spontaneous axonal regeneration in
      the peripheral nervous system through binding to various ligands that either
      inhibit or enhance their activation and signalling. Integrin biology is more
      complex in the central nervous system. Integrins receptors are transported into
      growing axons during development, but selective polarised transport of integrins
      limits the regenerative response in adult neurons. Manipulation of integrins and
      related molecules to control their activation state and localisation within axons
      is a promising route towards stimulating effective regeneration in the central
      nervous system.

PMID- 29446234
TI  - A natural antioxidant, tannic acid mitigates iron-overload induced hepatotoxicity
      in Swiss albino mice through ROS regulation.
AB  - Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups,
      is abundantly present in various medicinal plants. Previously TA has been
      investigated for its antimicrobial and antifungal properties. Being a large
      polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent
      antioxidant activities against reactive oxygen species (ROS), reactive nitrogen
      species (RNS) and as iron chelator in vitro thereby mitigating iron-overload
      induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in
      Swiss albino mice to induce iron-overload triggered hepatotoxicity, followed by
      oral administration of TA for remediation. After treatment, liver, spleen, and
      blood samples were processed from sacrificed animals. The liver iron, serum
      ferritin, serum markers, ROS, liver antioxidant status, and liver damage
      parameters were assessed, followed by histopathology and protein expression
      studies. Our results show that TA is a prominent ROS and RNS scavenger as well as
      iron chelator in vitro. It also reversed the ROS levels in vivo and restricted
      the liver damage parameters as compared to the standard drug, desirox. Moreover,
      this natural polyphenol exclusively ameliorates the histopathological and
      fibrotic changes in liver sections reducing the iron-overload, along with
      chelation of liver iron and normalization of serum ferritin. The protective role
      of TA against iron-overload induced apoptosis in liver was further supported by
      changed levels of caspase 3, PARP as well as Bax/BCl-2 ratio. Thus, TA can be
      envisaged as a better orally administrable iron chelator to reduce iron-overload
      induced hepatotoxicity through ROS regulation.

PMID- 29446235
TI  - Quantitative evaluation of the performance of different deformable image
      registration algorithms in helical, axial, and cone-beam CT images using a mobile
      phantom.
AB  - The goal of this project is to investigate quantitatively the performance of
      different deformable image registration algorithms (DIR) with helical (HCT),
      axial (ACT), and cone-beam CT (CBCT). The variations in the CT-number values and
      lengths of well-known targets moving with controlled motion were evaluated. Four
      DIR algorithms: Demons, Fast-Demons, Horn-Schunck and Lucas-Kanade were used to
      register intramodality CT images of a mobile phantom scanned with different
      imaging techniques. The phantom had three water-equivalent targets inserted in a
      low-density foam with different lengths (10-40 mm) and moved with adjustable
      motion amplitudes (0-20 mm) and frequencies (0-0.5 Hz). The variations in the CT
      number level, volumes and shapes of these targets were measured from the spread
      out of the CT-number distributions. In CBCT, most of the DIR algorithms were able
      to produce the actual lengths of the mobile targets; however, the CT-number
      values obtained from the DIR algorithms deviated from the actual CT-number of the
      targets. In HCT, the DIR algorithms were successful in deforming the images of
      the mobile targets to the images of the stationary targets producing the CT
      number values and lengths of the targets for motion amplitudes <20 mm. Similarly
      in ACT, all DIR algorithms produced the actual CT-number values and lengths of
      the stationary targets for low-motion amplitudes <15 mm. The optical flow-based
      DIR algorithms such as the Horn-Schunck and Lucas-Kanade performed better than
      the Demons and Fast-Demons that are based on attraction forces particularly at
      large motion amplitudes. In conclusion, most of the DIR algorithms did not
      reproduce well the CT-number values and lengths of the targets in images that
      have artifacts induced by large motion amplitudes. The deviations in the CT
      number values and variations in the volume of the mobile targets in the deformed
      CT images produced by the different DIR algorithms need to be considered
      carefully in the treatment planning for accurate dose calculation dose coverage
      of the tumor, and sparing of critical structures.

PMID- 29446236
TI  - Help me if you can: Psychological distance and help-seeking intentions in
      employee-supervisor relations.
AB  - Social support at work is considered useful in treating job-related stress, and
      supervisors' emotional support has been found to be the most effective source of
      support at work. But an understanding of what elements make employees use
      supervisors as a source of emotional support is lacking. The present qualitative
      study included in-depth interviews with 24 teachers and 12 principals and a focus
      group with 12 school counsellors. The findings pointed at 2 groups of
      determinants of subordinates' intentions of asking socioemotional help from
      supervisors. The structural-organizational factors included low formalization
      structure, supportive and open work climate, shared goals, and manager's
      professional expertise; the dyadic factors included quality of relationship and
      demographic similarity. The determinants reflected different dimensions of
      psychological distance forming a close construal level that played a central part
      in employees' viewing the supervisor as an accessible socioemotional resource.
      The role of construal fit is discussed.

PMID- 29446237
TI  - Going through the motions: incorporating movement analyses into disease research.
AB  - Though epidemiology dates back to the 1700s, most mathematical representations of
      epidemics still use transmission rates averaged at the population scale,
      especially for wildlife diseases. In simplifying the contact process, we ignore
      the heterogeneities in host movements that complicate the real world, and
      overlook their impact on spatiotemporal patterns of disease burden. Movement
      ecology offers a set of tools that help unpack the transmission process, letting
      researchers more accurately model how animals within a population interact and
      spread pathogens. Analytical techniques from this growing field can also help
      expose the reverse process: how infection impacts movement behaviours, and
      therefore other ecological processes like feeding, reproduction, and dispersal.
      Here, we synthesise the contributions of movement ecology in disease research,
      with a particular focus on studies that have successfully used movement-based
      methods to quantify individual heterogeneity in exposure and transmission risk.
      Throughout, we highlight the rapid growth of both disease and movement ecology
      and comment on promising but unexplored avenues for research at their overlap.
      Ultimately, we suggest, including movement empowers ecologists to pose new
      questions, expanding our understanding of host-pathogen dynamics and improving
      our predictive capacity for wildlife and even human diseases.

PMID- 29446238
TI  - Bacterial microleakage at the abutment-implant interface, in vitro study.
AB  - INTRODUCTION: In implant rehabilitation, a microspace is created at the abutment
      implant interface (AII). Previous research has shown that oral microbiome can
      proliferate in this microspace and affect periimplant tissues, causing
      inflammation in peri-implant tissues. Preventing microbial leakages through the
      AII is therefore an important goal in implantology. OBJECTIVE: To determine the
      presence of marginal bacterial microleakage at the AII according to the torque
      applied to the prosthetic implant in vitro. MATERIAL AND METHODS: Twenty-five
      Ticare Inhex internal conical implants (MG Mozo-Grau, Valladolid, Espana) were
      connected to a prosthetic abutment using torques of <10, 10, 20, 30, and 30 N and
      then sealed. The samples were submitted to cycles of occlusal loads and
      thermocycling, then one sample of each group was observed by micro TC, while the
      rest were mounted on devices according to the bacterial leakage model with
      Porphyromonas gingivalis. RESULTS: Bacterial leakage was observed only in the <10
      and 10 N torque samples, and the same groups presented poor abutment/implant
      adjustment as determined by micro-CT. CONCLUSION: The different torques applied
      to the abutment-implant system condition the bacterial leakage at the implant
      interface. No microleakage was observed at 20 and 30 N.

PMID- 29446239
TI  - Authors' reply re: Medical therapy for preventing recurrent endometriosis after
      conservative surgery: a cost-effectiveness analysis.

PMID- 29446241
TI  - Is it time to move towards non-invasive prenatal screening for Down syndrome and
      screening for pre-eclampsia?

PMID- 29446242
TI  - Evaluation and validation of an ion mobility quadrupole time-of-flight mass
      spectrometry pesticide screening approach.
AB  - An ion mobility quadrupole time-of-flight mass spectrometry-based pesticide
      suspect screening methodology was developed and validated covering 20 plant
      derived food matrices deriving from six commodity groups of different complexity
      according to the actual European Commission document SANTE/11813/2017 applying a
      QuEChERS sample preparation protocol. The method combines ultra-performance
      liquid chromatography, traveling wave ion mobility, and quadrupole time-of-flight
      mass spectrometry. Besides the determination of the physicochemical property
      collision cross-section and the establishment of a corresponding scientific
      suspect screening database comprising 280 pesticides for several pesticides,
      different protomers, sodium adducts, as well as dimers were identified in ion
      mobility spectrometry traces. Additionally, collision cross-section values were
      included in the validation requirements regarding chromatography and mass
      spectrometry for the detection of pesticides. A collision cross-section value
      window was analyzed within a tolerable error of +/-2%. For this cross-matrix
      validation, screening detection limits were determined at concentration levels of
      0.100 mg/kg (84% of the original pesticide scope), 0.010 mg/kg (56%), and 0.001
      mg/kg (21%). By application of ion mobility spectrometry, the compound
      identification was improved due to independence of commodity of concern and
      concentration levels of analyte molecules, as false assignments are reduced by
      application of a collision cross-section range.

PMID- 29446244
TI  - Systematic review of the use of Statistical Process Control methods to measure
      the success of pressure ulcer prevention.
AB  - Successful prevention of pressure ulcers is the end product of a complex series
      of care processes including, but not limited to, the assessment of vulnerability
      to pressure damage; skin assessment and care; nutritional support; repositioning;
      and the use of beds, mattresses, and cushions to manage mechanical loads on the
      skin and soft tissues. The purpose of this review was to examine where and how
      Statistical Process Control (SPC) measures have been used to assess the success
      of quality improvement initiatives intended to improve pressure ulcer prevention.
      A search of 7 electronic bibliographic databases was performed on May 17th, 2017,
      for studies that met the inclusion criteria. SPC methods have been reported in 9
      publications since 2010 to interpret changes in the incidence of pressure ulcers
      over time. While these methods offer rapid interpretation of changes in incidence
      than is gained from a comparison of 2 arbitrarily selected time points pre- and
      post-implementation of change, more work is required to ensure that the clinical
      and scientific communities adopt the most appropriate SPC methods.

PMID- 29446243
TI  - Reproductive health in women following abdominal organ transplant.
AB  - Fertility is commonly impaired in women with end-stage kidney and liver disease,
      although most women will have restoration of fertility within 1 year of
      transplant. Family planning is therefore critical to discuss with reproductive
      aged transplant recipients in the early posttransplant period, in order to ensure
      timely initiation of contraception, and optimal timing for conception. For women
      seeking pregnancy, the risks to the mother, graft, and baby should be discussed,
      including evaluation of immunosuppression safety and potential for adjusting
      medications prior to conception. With an increasing number of transplant patients
      now breastfeeding, immunosuppression safety in lactation continues to carry great
      importance.

PMID- 29446245
TI  - Differential metabolic effects of constant moderate versus high intensity
      interval training in high-fat fed mice: possible role of muscle adiponectin.
AB  - Exercise regimens may have differing effects in the presence of obesity. In
      addition to being fat derived, adiponectin has recently been described as a
      myokine that regulates insulin sensitivity, which may link to exercise-related
      metabolic benefits in obesity. Whether skeletal muscle adiponectin varies in
      different exercise modalities is unclear. This study investigated the comparative
      effects of 10 weeks of endurance constant-moderate intensity exercise (END) with
      high intensity interval training (HIIT), on metabolic outcomes, including muscle
      adiponectin in a mouse model of diet-induced obesity. Ten-week-old male C57BL/6
      mice were fed a high-fat diet (HFD) (45% FAT) or standard CHOW diet ab libitum
      and underwent one of three training regimes: (1) no exercise, (2) END, or (3)
      HIIT (8 bouts of 2.5 min with eight periods of rest of 2.5 min) for 10 weeks (3 *
      40 min sessions/week). Chow-fed mice acted as controls. Compared with HFD alone,
      both training programs similarly protected against body weight gain (HFD = 45 +/-
      2; END = 37 +/- 2; HIIT = 36 +/- 2 g), preserved lean/fat tissue mass ratio (HFD
      = 0.64 +/- 0.09; END = 0.34 +/- 0.13; HIIT = 0.33 +/- 0.13), and improved blood
      glucose excursion during an insulin tolerance test (HFD = 411 +/- 54; END = 350
      +/- 57; HIIT = 320 +/- 66 arbitrary units [AU]). Alterations in fasting glycemia,
      insulinemia, and AST/ALT ratios were prevented only by END. END, but not HIIT
      increased skeletal muscle adiponectin mRNA (14-fold; P < 0.05) and increased
      protein content of high molecular weight (HMW) adiponectin (3.3-fold), whereas
      HIIT induced a milder increase (2.4-fold). Compared with HFD, neither END nor
      HIIT altered circulating low (LMW) or high (HMW) molecular weight adiponectin
      forms. Furthermore, only END prevented the HFD downregulation of PGC1alpha (P <
      0.05) mRNA levels downstream of muscle adiponectin. These data show that
      different training programs affect muscle adiponectin to differing degrees.
      Together these results suggest that END is a more effective regimen to prevent
      HFD-induced metabolic disturbances in mice.

PMID- 29446246
TI  - Improvement of cardiomyocyte function by in vivo hexarelin treatment in
      streptozotocin-induced diabetic rats.
AB  - Diabetic cardiomyopathy is characterized by diastolic and systolic cardiac
      dysfunction, yet no therapeutic drug to specifically treat it. Hexarelin has been
      demonstrated to improve heart function in various types of cardiomyopathy via its
      receptor GHS-R. This experiment aims to test the effect of hexarelin on
      cardiomyocytes under experimental diabetes. Streptozotocin (STZ, 65 mg/kg)
      induced diabetic rat model was employed with vehicle injection group as control.
      Daily hexarelin (100 MUg/kg) treatment was performed for 2 weeks after 4-week STZ
      induced diabetes. Cardiomyocytes were isolated by enzyme treatment under O2 
      saturated perfusion for single-cell shortening, [Ca2+ ]i transient, and
      electrophysiology recordings. GHS-R expression and apoptosis-related signaling
      proteins Bax, Bcl-2, caspase-3 and 9, were assessed by western blot. Experimental
      data demonstrated a reduced cell contraction and relaxation in parallel with
      depressed rise and fall of [Ca2+ ]i transients in diabetic cardiomyocytes.
      Hexarelin reversed the changes in both contraction and [Ca2+ ]i . Action
      potential duration and transient outward potassium current (Ito ) density were
      dramatically increased in diabetic cardiomyocytes and hexarelin treatment reverse
      such changes. Upregulated GHS receptor (GHS-R) expression was observed in both
      control and diabetic groups after hexarelin treatment, which also caused
      antiapoptotic changes of Bax, Bcl-2, caspase-3 and 9 expression. In STZ-induced
      diabetic rats, hexarelin is able to improve cardiomyocyte function through
      recovery of Ito K+ currents, intracellular Ca2+ homeostasis and antiapoptotic
      signaling pathways.

PMID- 29446247
TI  - Molecular diagnostic techniques in cytopathology: From the bench to the patient's
      bedside.
AB  - Molecular techniques are increasingly used in everyday practice for patient
      diagnosis and also to guide therapy. Their application in cytological specimens
      can allow a more cost-effective management with fewer risks. However,
      standardized protocols are needed to guarantee accurate and reproducible results.
      We herein report five practical examples of the application of ancillary
      techniques in cytopathology and review the literature on the issue, highlighting
      the practical aspects of sample management.

PMID- 29446248
TI  - Cytological features of small cell carcinoma of the ovary-hypercalcemic
      type/malignant ovarian rhabdoid tumor in ascitic fluid.

PMID- 29446249
TI  - Serological responses to revaccination against HBV in HIV-positive patients born
      in the era of nationwide neonatal HBV vaccination.
AB  - BACKGROUND: Serological responses to revaccination against hepatitis B virus
      (HBV) are unclear in HIV-positive adults who had undergone neonatal HBV
      vaccination and whose antibodies against HBV had waned in the era of combination
      antiretroviral therapy (cART). METHODS: Between 2000 and 2017, 666 HIV-positive
      men who have sex with men (MSM) who were born after 1986, when nationwide
      neonatal HBV vaccination programme was implemented in Taiwan, were included for
      analyses. A serological response was defined when a hepatitis B surface antibody
      (anti-HBs) titre >=10 mIU/mL was measured 4-24 weeks after the third dose of HBV
      vaccination. RESULTS: During the study period, 295 (48.7%) HIV-positive MSM (mean
      age, 23.2 years) who had lost HBV seroprotection were eligible for revaccination;
      171 (58.0%) received at least 1 dose (20-MUg) of HBV vaccine and 116 (39.3%)
      completed the 3-dose schedule. The serological response rate to 3 doses of HBV
      revaccination was 74.0% and the rate of high-titre response (anti-HBs titre >=100
      mIU/mL) was 46.0%. The CD4 count before the first dose (per 50-cell/MUL
      increment, adjusted odds ratio, 1.14; 95% confidence interval, 1.01-1.29) was
      positively associated with the serological response. The incident rate of HBV
      infection was 9.2 per 1000 person-years of follow-up among the patients who were
      non-responders after revaccination. CONCLUSIONS: Despite HBV vaccination in the
      neonatal period, the serological response rate to HBV revaccination in HIV
      positive MSM was modest and could wane rapidly. Regular testing of anti-HBs
      should be integrated into the HIV care despite cART containing HBV-active agents.

PMID- 29446250
TI  - How do Small Groups Promote Behaviour Change? An Integrative Conceptual Review of
      Explanatory Mechanisms.
AB  - BACKGROUND: Small groups are used to promote health, well-being, and personal
      change by altering members' perceptions, beliefs, expectations, and behaviour
      patterns. An extensive cross-disciplinary literature has articulated and tested
      theories explaining how such groups develop, function, and facilitate change. Yet
      these theoretical understandings are rarely applied in the development,
      description, and evaluation of health-promotion, group-based, behaviour-change
      interventions. METHODS: Medline database, library catalogues, search engines,
      specific journals and reference lists were searched for relevant texts. Texts
      were reviewed for explanatory concepts or theories describing change processes in
      groups, which were integrated into the developing conceptual structure. This was
      designed to be a parsimonious conceptual framework that could be applied to
      design and delivery. RESULTS: Five categories of interacting processes and
      concepts were identified and defined: (1) group development processes, (2)
      dynamic group processes, (3) social change processes, (4) personal change
      processes, and (5) group design and operating parameters. Each of these
      categories encompasses a variety of theorised mechanisms explaining individual
      change in small groups. CONCLUSION: The final conceptual model, together with the
      design issues and practical recommendations derived from it, provides a practical
      basis for linking research and theory explaining group functioning to optimal
      design of group-based, behaviour-change interventions.

PMID- 29446251
TI  - A novel technique for en bloc kidney transplantation from infant donors with
      extremely low body weight by using the distal abdominal aorta as an outflow
      tract.
AB  - Pediatric kidney donors remain underutilized due to the high risk of
      postoperative thrombosis. To address this problem, we developed a novel en bloc
      kidney transplantation technique using donor thoracic aorta and the distal
      abdominal aorta as inflow and outflow tracts, respectively. Briefly, eight
      kidneys from deceased infant donors under five months old and with low body
      weight (1.9-4.9 kg) were transplanted en bloc into four pediatric and four adult
      patients. The donor's common iliac artery or external iliac artery was
      anastomosed to the recipient's distal external iliac artery or inferior
      epigastric artery, respectively, as an outflow tract. Recipients received
      basiliximab or antithymocyte globulin as induction therapy followed by
      tacrolimus, mycophenolate mofetil, and prednisone but without prophylactic
      anticoagulation. Delayed graft function was observed in one patient but was
      reversed at 90 days posttransplant. Two patients had urine leakage, which was
      cured by conservative treatment. Two recipients developed lung infections that
      eventually cleared. No patients experienced posttransplant vascular thrombosis.
      After 1-1.5 years of follow-up, all patients are well and have normal serum
      creatinine levels. In conclusion, this novel en bloc kidney transplantation
      technique using a modified arterial inflow and outflow tract can prevent vascular
      thrombosis and provide adequate graft function.

PMID- 29446252
TI  - What is the effect of exercise on wound healing in patients with venous leg
      ulcers? A systematic review.
AB  - Standard best practice for the treatment of venous leg ulcers (VLUs) is
      compression bandaging of the lower leg to reduce hydrostatic pressure. There is
      considerable variation in reported healing rates when using this gold-standard
      approach; therefore, a systematic and robust evaluation of other interventions is
      required. Exercise interventions, in addition to standard compression therapy,
      could improve wound-healing time and prevent their recurrence. We have conducted
      a systematic review to examine the effects of exercise on wound characteristics,
      including time to heal, size and recurrence, pain, quality of life, adverse
      events, and economic outcomes. This review was registered with PROSPERO
      2016:CRD42016046407. A systematic search of Ovid Medline, Ovid EMBASE, Ovid
      CINAHL, The Cochrane Library, PsycINFO, Web of Science, and PEDro was conducted
      on January 30, 2017, for randomised control trials to examine the effects of
      exercise on time to heal, size and recurrence, pain, quality of life, adverse
      events, and economic outcomes. Six studies met the inclusion criteria, but all
      had design flaws leading to biases, most commonly performance and selective
      reporting bias. Three studies compared a progressive resistance exercise
      programme (PREG) plus compression with compression alone for a period of 12
      weeks. Low-quality evidence indicates the following: possibly no difference in
      the proportion of ulcers healed (risk ratio [RR] 1.14, 95% CI 0.71 to 1.84, I2
      36%; 3 trials, 116 participants); probably no difference in quality of life (mean
      difference [MD] 3 points better on 100 point scale with exercise, 95% CI -1.89 to
      7.89, 1 trial, 59 participants); possible increase in the risk of adverse events
      with exercise (OR 1.32, 95% CI 0.95 to 1.85, 1 RCT, 40 participants); and no
      difference in ankle range of motion and calf muscle pump. Evidence was downgraded
      due to susceptibility to bias and imprecision. Recurrence, pain, and economic
      outcomes were not measured in these trials, and time to healing was measured but
      not fully reported in 1 trial. We are uncertain of the effects of other
      interventions (community-based exercise and behaviour modification, ten thousand
      steps, supervised vs unsupervised exercise) due to the availability of low- or
      very low-quality evidence only from single trials. The review highlights the need
      for further research, with larger sample sizes, to properly address the
      significance of the effect of exercise on VLU wound characteristics.

PMID- 29446253
TI  - Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing
      cell EMT via MAPK signaling.
AB  - Surgical results for intrahepatic cholangiocarcinoma (ICC) remain unsatisfactory
      due to the high rate of recurrence. Here, we investigated that the expression and
      roles of tripartite motif-containing protein 44 (TRIM44) in human ICCs. Firstly,
      TRIM44 expression was analyzed in several kinds of cancers by referring to public
      Oncomine database, and the expressions of TRIM44 mRNA and protein were tested in
      ICC and corresponding paratumorous tissues. Secondly, functions and mechanisms of
      TRIM44 in ICC cells were further evaluated by TRIM44 interference and cDNA
      transfection. Finally, the prognostic role of TRIM44 was assessed by Kaplan-Meier
      and Cox regression. We found that TRIM44 expression was upregulated in ICC
      tissues compared with corresponding paratumorous tissues, which were consistent
      with the results from the public cancer database. Knockdown of TRIM44 repressed
      the invasion and migration of ICC cells, while increased the ICC cell apoptosis.
      Additionally, high level of TRIM44 was shown to induce ICC cell epithelial to
      mesenchymal transition (EMT). Mechanistically, a high level of TRIM44 was found
      to activate MAPK signaling, and a MEK inhibitor, AZD6244, reversed cell EMT and
      apoptosis endowed by TRIM44 overexpression. Clinically, TRIM44 expression was
      positively associated with large tumor size (P = 0.035), lymphatic metastasis (P
      = 0.008) and poor tumor differentiation (P = 0.036). Importantly, patients in
      TRIM44high group had shorter overall survival and higher cumulative rate of
      recurrence than patients in TRIM44low group. Our results suggest elevated TRIM44
      promotes ICC development by inducing cell EMT and apoptosis resistance, and
      TRIM44 is a valuable prognostic biomarker and promising therapeutic target of
      ICC.

PMID- 29446254
TI  - Heart failure: a weak link in CHA2 DS2 -VASc.
AB  - AIMS: In atrial fibrillation, stroke risk is assessed by the CHA2 DS2 -VASc
      score. Heart failure is included in CHA2 DS2 -VASc, but the rationale is
      uncertain. Our objective was to test if heart failure is a risk factor for
      stroke, independent of other risk factors in CHA2 DS2 -VASc. METHODS AND RESULTS:
      We studied 300 839 patients with atrial fibrillation in the Swedish Patient
      Register 2005-11. Three definitions of heart failure were used in order to assess
      the robustness of the results. In the main analysis, heart failure was defined by
      a hospital discharge diagnosis of heart failure as first or second diagnosis and
      a filled prescription of a diuretic within 3 months before index + 30 days. The
      second definition counted first or second discharge diagnoses <1 year before
      index + 30 days and the third definition any heart failure diagnosis in open or
      hospital care before index + 30 days. Associations with outcomes were assessed
      with multivariable Cox analyses. Patients with heart failure were older (80.5 vs.
      74.0 years, P < 0.001) and had higher CHA2 DS2 -VASc score (4.4 vs. 2.7, P <
      0.001). The 1 year incidence of ischaemic stroke without warfarin was 4.4% with
      heart failure and 3.1% without. Adjustment for the cofactors in CHA2 DS2 -VASc
      eradicated the difference in stroke risk between patients with and without heart
      failure (hazard ratio 1.01 with 95% confidence interval 0.96-1.05). The area
      under the receiver operating characteristic curve for CHA2 DS2 -VASc was not
      improved by points for heart failure. CONCLUSIONS: A clinical diagnosis of heart
      failure was not an independent risk factor for stroke in patients with atrial
      fibrillation, which may have implications for anticoagulation management.

PMID- 29446255
TI  - Potential genetic markers for nonsyndromic oral clefts in the Brazilian
      population: A systematic review and meta-analysis.
AB  - BACKGROUND: Although various genes and genomic regions were described as of
      susceptibility for nonsyndromic oral clefts (NOC), recent reports have
      demonstrated significant interethnic variations in the genetic predisposition, a
      situation that affects the Brazilian population, one of the most admixed
      populations in the world. Therefore, the purpose of this review was to describe
      the available information on genetic risk markers for NOC in the Brazilian
      population. METHODS: A systematic search of the literature was performed using
      LILACS, LIVIVO, PubMed, Scopus, and Web of Science databases, and studies that
      investigated genetic susceptibility markers for NOC in the Brazilian population
      were retrieved. Markers with enough statistical data were subjected to meta
      analysis using random- or fixed-effects model with odds ratio (OR) and 95%
      confidence intervals (95% CI) as effect measures. RESULTS: Forty-nine studies
      conducted since 1999 were found, and in these 114 markers were evaluated
      throughout case-control or family-based approaches. Most of the studies were
      conducted with patients affected by nonsyndromic cleft lip with or without cleft
      palate (NSCL +/- P), and 79 markers (69.3%) were evaluated by a single study
      only. Meta-analysis was performed with nine markers, and the most promising
      results were obtained for IRF6 (rs642961), 8q24 (rs987525 and rs1530300) and
      MTHFR (rs1801133), which were associated with increased risk for NSCL +/- P, and
      for BMP4 (rs17563) that showed a protective effect for NSCL +/- P. CONCLUSION: A
      large number of genetic markers distributed in several genes/loci was associated
      with NOC in the Brazilian population, but in general the original studies
      included limited number of samples and unsatisfactory protocols. The classical
      risk markers located in IRF6 and 8q24 showed promising results as well as
      rs1801133 in MTHFR and rs17563 in BMP4, and they should be validated in larger
      and multicenter studies taking in consideration the variations in the
      miscegenation of Brazilian population.

PMID- 29446256
TI  - Using a Vancomycin PBPK Model in Special Populations to Elucidate Case-Based
      Clinical PK Observations.
AB  - Simultaneous changes in several physiological factors may contribute to the large
      pharmacokinetic (PK) variability of vancomycin. This study was designed to
      systematically characterize the effects of multiple physiological factors to the
      altered PK of vancomycin observed in special populations. A vancomycin
      physiologically based pharmacokinetic (PBPK) model was developed as a PK
      simulation platform to quantitatively assess the effects of changes in
      physiologies to the PK profiles. The developed model predicted the concentration
      time profiles in healthy adults and diseased patients. The implementation of
      developmental changes in both renal and non-renal elimination pathways to the
      pediatric model improved the predictability of vancomycin clearance. Simulated PK
      profiles with a 50% decrease in cardiac output (peak plasma concentration (Cmax
      ), 59.9 ng/mL) were similar to those observed in patients before bypass surgery
      (Cmax , 55.1 ng/mL). The PBPK modeling of vancomycin demonstrated its potential
      to provide mechanistic insights into the altered disposition observed in patients
      who have changes in multiple physiological factors.

PMID- 29446257
TI  - Utilization of direct smears of thyroid fine-needle aspirates for ancillary
      molecular testing: A comparison of two proprietary testing platforms.
AB  - BACKGROUND: Ancillary molecular testing has been recommended for thyroid fine
      needle aspirates (FNA) with indeterminate cytologic diagnoses. Rosetta Genomics
      and Interpace Diagnostics have developed assays that can utilize direct smears as
      the testing substrate. METHODS: A retrospective study of indeterminate thyroid
      FNAs with known histologic follow-up was performed. One Diff-Quik-stained smear
      and one Papanicolaou-stained smear with similar cellularity (at least 60-100
      lesional cells) from each case were sent to Rosetta and Interpace, respectively,
      for analysis. The results were directly compared and correlated with the final
      histopathology. Neither company was aware of the follow-up histologic findings in
      these cases. RESULTS: A total of 10 thyroid FNAs were identified from our 2015
      files. The cytologic diagnoses included follicular lesion of undetermined
      significance (FLUS, n = 5), follicular neoplasm/suspicious for follicular
      neoplasm (FN/SFN, n = 4), and suspicious for malignancy (SM, n = 1). Of the seven
      cases with benign histology, six smears were classified as benign by the
      RosettaGX microRNA classifier, and one case was designated as suspicious. Five
      cases were negative by both ThyGenX oncogene panel and ThyraMIR microRNA
      classifier. One case was negative by ThyGenX and positive on follow-up ThyraMIR,
      and one case was positive for KRAS mutation and positive on ThyraMIR. Both the
      RosettaGX and ThyGenX/ThyraMIR tests demonstrated positive results for the three
      histologically malignant cases. CONCLUSION: This study demonstrates that two
      molecular testing platforms performed equally well using our stained direct
      smears. Both molecular tests revealed a 100% negative predictive rate. RosettaGX
      showed a 75% positive predictive value in comparison to 60% for ThyGenX/ThyraMIR.

PMID- 29446258
TI  - Corrigendum.

PMID- 29446259
TI  - Corrigendum.

PMID- 29446260
TI  - QM/MM Studies on Photoisomerization Dynamics of Azobenzene Chromophore Tethered
      to a DNA Duplex: Local Unpaired Nucleobase Plays a Crucial Role.
AB  - The photoresponsive azobenzene-tethered DNAs have received growing experimental
      attention because of their potential applications in biotechnology and
      nanotechnology; however, little is known about the initial photoisomerization of
      azobenzene in these systems. Herein we have employed quantum mechanics/molecular
      mechanics (QM/MM) methods to explore the photoisomerization dynamics of an
      azobenzene-tethered DNA duplex. We find that in the S1 state the trans-cis
      photoisomerization path is much steeper in DNA than in vacuo, which makes the
      photoisomerization much faster in the DNA environment. This acceleration is
      primarily caused by complex steric interactions between azobenzene and the nearby
      unpaired thymine nucleobase, which also change the photoisomerization mechanism
      of azobenzene in the DNA duplex.

PMID- 29446261
TI  - Enhanced linear-array photoacoustic beamforming using modified coherence factor.
AB  - Photoacoustic imaging (PAI) is a promising medical imaging modality providing the
      spatial resolution of ultrasound imaging and the contrast of optical imaging. For
      linear-array PAI, a beamformer can be used as the reconstruction algorithm. Delay
      and-sum (DAS) is the most prevalent beamforming algorithm in PAI. However, using
      DAS beamformer leads to low-resolution images as well as high sidelobes due to
      nondesired contribution of off-axis signals. Coherence factor (CF) is a weighting
      method in which each pixel of the reconstructed image is weighted, based on the
      spatial spectrum of the aperture, to mainly improve the contrast. We demonstrate
      that the numerator of the formula of CF contains a DAS algebra and propose the
      use of a delay-multiply-and-sum beamformer instead of the available DAS on the
      numerator. The proposed weighting technique, modified CF (MCF), has been
      evaluated numerically and experimentally compared to CF. It was shown that MCF
      leads to lower sidelobes and better detectable targets. The quantitative results
      of the experiment (using wire targets) show that MCF leads to for about 45% and
      40% improvement, in comparison with CF, in the terms of signal-to-noise ratio and
      full-width-half-maximum, respectively.

PMID- 29446262
TI  - Lens implementation on the GATE Monte Carlo toolkit for optical imaging
      simulation.
AB  - Optical imaging techniques are widely used for in vivo preclinical studies, and
      it is well known that the Geant4 Application for Emission Tomography (GATE) can
      be employed for the Monte Carlo (MC) modeling of light transport inside
      heterogeneous tissues. However, the GATE MC toolkit is limited in that it does
      not yet include optical lens implementation, even though this is required for a
      more realistic optical imaging simulation. We describe our implementation of a
      biconvex lens into the GATE MC toolkit to improve both the sensitivity and
      spatial resolution for optical imaging simulation. The lens implemented into the
      GATE was validated against the ZEMAX optical simulation using an US air force
      1951 resolution target. The ray diagrams and the charge-coupled device images of
      the GATE optical simulation agreed with the ZEMAX optical simulation results. In
      conclusion, the use of a lens on the GATE optical simulation could improve the
      image quality of bioluminescence and fluorescence significantly as compared with
      pinhole optics.

PMID- 29446263
TI  - Pulsed terahertz imaging of breast cancer in freshly excised murine tumors.
AB  - This paper investigates terahertz (THz) imaging and classification of freshly
      excised murine xenograft breast cancer tumors. These tumors are grown via
      injection of E0771 breast adenocarcinoma cells into the flank of mice maintained
      on high-fat diet. Within 1 h of excision, the tumor and adjacent tissues are
      imaged using a pulsed THz system in the reflection mode. The THz images are
      classified using a statistical Bayesian mixture model with unsupervised and
      supervised approaches. Correlation with digitized pathology images is conducted
      using classification images assigned by a modal class decision rule. The
      corresponding receiver operating characteristic curves are obtained based on the
      classification results. A total of 13 tumor samples obtained from 9 tumors are
      investigated. The results show good correlation of THz images with pathology
      results in all samples of cancer and fat tissues. For tumor samples of cancer,
      fat, and muscle tissues, THz images show reasonable correlation with pathology
      where the primary challenge lies in the overlapping dielectric properties of
      cancer and muscle tissues. The use of a supervised regression approach shows
      improvement in the classification images although not consistently in all tissue
      regions. Advancing THz imaging of breast tumors from mice and the development of
      accurate statistical models will ultimately progress the technique for the
      assessment of human breast tumor margins.

PMID- 29446264
TI  - [Assessment of non-carcinogenic risk for the health of the child population under
      the consumption of drinking water].
AB  - In the article there are given results of the evaluation of non-carcinogenic
      risks for the health of the child population residing in different areas
      (districts) of the city of Kazan with the aim of the subsequent comprehensive
      assessment of the pollutants in drinking water. Assessment of the risk for the
      human health was performed correspondingly to with the P 2.1.10.1920-04 for oral
      route of exposure in accordance to the chemical composition of drinking water
      with account for the standard and regional factors of the exposure. The results
      of the risk assessment under the consumption of drinking tap water by the child
      population with localized place of residence permit to reveal areas with a high
      level of health risk in the city. The screening assessment of carcinogenic risk
      due to the consumption of chemicals with drinking water revealed differences in
      regional and standard values of the exposure factors. This affects both on the
      value of the chronic average daily intake of chemical contaminants in drinking
      water and the level of risk under the consumption of drinking water by the child
      population.

PMID- 29446265
TI  - [Introduction of hazard analysis and critical control points (HACCP) principles
      at the flight catering food production plant].
AB  - In the article there is considered the quality control and safety system
      implemented in the one of the largest flight catering food production plant for
      airline passengers and flying squad. The system for the control was based on the
      Hazard Analysis And Critical Control Points (HACCP) principles and developed
      hygienic and antiepidemic measures. There is considered the identification of
      hazard factors at stages of the technical process. There are presented results of
      the analysis data of monitoring for 6 critical control points over the five-year
      period. The quality control and safety system permit to decline food
      contamination risk during acceptance, preparation and supplying of in-flight
      meal. There was proved the efficiency of the implemented system. There are
      determined further ways of harmonization and implementation for HACCP principles
      in the plant.

PMID- 29446266
TI  - [Regional features of food standards and health risks associated with chemical
      contamination of food].
AB  - In the article there are presented results of a study of the balance of food
      consumption by the population of the Voronezh region, the assessment of the level
      of contamination of food products and both carcinogenic and non-carcinogenic and
      public health risk caused by this contamination. There was evaluated the level of
      nutrition-dependent diseases. A special feature of this study is a comparative
      analysis of data obtained during the two five-year periods of 1995-1999 and 2010
      2014, that permitted to reveal changes in food consumption, the dynamics of
      morbidity rate associated with the nutritional factor.

PMID- 29446267
TI  - Skin irritation from a facial mask in Class III malocclusion: evaluation of
      individual silicone chin cups in a group of 100 children.
AB  - BACKGROUND: Reverse headgear (a facial mask) is one of the most frequently used
      interceptive orthodontic devices in patients with Class III malocclusion. It is a
      simple device but may present some drawbacks related to pressure on the skin
      generated by the forehead and chin supports linked to the maxillary intraoral
      appliance by elastics. This can cause injury to the chin and lips. METHODS:
      Patients between 7 and 8 years of age were selected from the Unit of Pediatric
      Dentistry. Orthopedic therapy with a rapid palatal expander and reverse headgear
      was prescribed for all subjects. The patients were divided into two groups: those
      who used a facial mask without a silicone chin cup and those who used a facial
      mask with a silicone chin cup. RESULTS: Two-hundred subjects including 90 male
      patients and 110 female patients were enrolled. The groups that used a facial
      mask with and without a silicone chin cup included 100 patients each. The
      percentage of subjects without irritation was significantly greater in the group
      with a silicone chin cup than in the group without a silicone chin cup.
      CONCLUSIONS: The authors propose a simple and effective solution to prevent skin
      irritation on the chin caused by a facial mask. A chin mask is a custom solution
      that can prevent injury to the chin during treatment when coupled with facial
      mask therapy.

PMID- 29446268
TI  - Tooth color changes and sensitivity in patients undergoing dental bleaching with
      10% hydrogen peroxide using customized trays or strips: a randomized clinical
      trial.
AB  - BACKGROUND: This paper aimed to compare the tooth color changes and sensitivity
      in patients undergoing dental bleaching with 10% hydrogen peroxide using
      customized trays or strips as delivering systems. METHODS: A total of 50 patients
      aged between 18-30 years old were assigned into two groups (N.=25) according to
      the bleaching treatment: tray (TB) or strips (SB). For both techniques, the
      patients underwent a 30-minute application of 10% hydrogen peroxide twice a day
      for seven days. Tooth color was evaluated before, 3 and 7 days of treatment, and
      14 days after bleaching using a tooth color shade guide (VITA(r) shade). Tooth
      sensitivity was assessed using the Visual Analogue Scale (VAS). The values
      obtained from the color changes and tooth sensitivity were statistically analyzed
      (alpha=5%). RESULTS: For both groups, there was a significant difference on the
      tooth color before and after bleaching (P<0.001), although there was no
      significant difference between them (P=0.4215). The SB group exhibited a lower
      frequency of sensitivity (50.2%) compared to the TB group (70.2%) (P<0.001).
      However, the highest number of individuals reporting score 1 of sensitivity was
      found in the SB group (37.3%) compared to the TB group (20.9%) (P<0.001). For the
      other scores, there were no differences between the SB and TB groups, with
      results of 9.8% and 8.4% for score 2 (P=0.744) and 2.7% and 0.5% for score 3
      (P=0.122). CONCLUSIONS: The bleaching effect of 10% hydrogen peroxide is not
      influenced by the delivering system (tray or strips). Even though the technique
      with strips was associated to a lower frequency of dental sensitivity, the peak
      level of pain was greater when compared to the technique using trays.

PMID- 29446269
TI  - A self-report joint damage and musculoskeletal disorders data among dentists: a
      cross-sectional study.
AB  - BACKGROUND: Musculoskeletal disorders (MSD) are an occupational health problem
      that demands a high cost and may also reduce the quality of life and productivity
      of the dentists. The aim of this study was to evaluate the prevalence of MSD and
      its association with self-reported joint damage in dentists from Sao Paulo
      (Brazil). METHODS: This was a cross-sectional study performed from two self
      administered questionnaires - the Nordic Musculoskeletal Questionnaire and the
      other containing demographic and occupational data - in 6072 dentists. Between
      April and May 2014, 5885 questionnaires were distributed via e-mail through Sao
      Paulo Regional Board of Dentistry (CRO-SP) and 187 in Congress and public
      offices. Multivariable logistic regression was used to assess the association
      between explanatory variables (sex, age, level of education, duration of practice
      in years, number of patients seen per day, previous receipt of information about
      ergonomics, physical activity, and the presence of joint damage) and MSD.
      RESULTS: Two hundred eighty-six valid questionnaires were returned. The
      prevalence of MSD was 63.6% (N.=182). Multivariable logistic regression showed
      that only the factor of self-reported joint damage has a significant association
      with MSD (OR 0.001; 95% CI: 0.000-0.007). Concerning the self-reported joint
      damage (60.1%), the carpal tunnel syndrome was the most frequent (13.2%).
      CONCLUSIONS: The prevalence of MSD in dentists from Sao Paulo is high, and carpal
      tunnel syndrome is the most common self-reported joint damage.

PMID- 29446270
TI  - A comparative evaluation of APF gel, CPP/ACP paste alone and in combination with
      carbon dioxide laser on human enamel resistance to acid solubility using atomic
      absorption spectrometry: an in-vitro study.
AB  - BACKGROUND: The aim of this study was to compare the effects of acidulated
      phosphate fluoride (APF) gel, calcium phosphopeptide-amorphous calcium phosphate
      (CPP/ACP) paste alone and in combination with CO2 laser on the resistance of
      enamel to acid solubility. METHODS: Ninety enamel sections were obtained from 15
      extracted teeth and were randomly assigned to six groups: 1) control group; 2)
      APF group; 3) CPP-ACP group; 4) CO2 laser group; 5) APF + CO2 group; and 6) CPP
      ACP + CO2 group. The specimens were individually demineralized in 0.1 M lactic
      acid solution with adjusted pH of 4.8 for 24h at 37 oC. The acid solubility was
      determined using atomic absorption spectrometry. Statistical analysis was done
      using one-way ANOVA and Tukey-Kramer post hoc test (P<0.05). RESULTS: The average
      extent of calcium ion released (ppm) was estimated as follow: group 1: 6.974+/
      1.757, group 2: 5.363+/-1.383, group 3: 6.962+/-1.489, group 4: 6.890+/-1.560,
      group 5: 4.803+/-1.080 and group 6: 6.789+/-1.218. Based on the between-group
      comparison results, group 2 and group 5 showed significant differences with the
      other groups. CONCLUSIONS: Under the studied conditions, only, the APF group
      alone and in combination with CO2 laser could decrease enamel acid solubility.

PMID- 29446271
TI  - An unusual presentation of subacute necrotizing sialadenitis.

PMID- 29446272
TI  - [The system of the quality control and the safety of baby food, the prospects of
      its development].
AB  - In the article there is considered the substantiation of raise demands to the
      chemical composition of children's food and indices of their safety, with taking
      into account the immaturity of metabolic and physiological processes and
      limitations of "depot" of nutrients in babies. Based on research results of
      leading experts in the field of children's nutritiology and according to the
      recommendations of the Codex Alimentarius of the Commission of FAO/WHO, ESPGHAN
      Committee on Nutrition, the EFSA recommendations and EUDirectives there were
      specified requirements for the ingredient composition, content of essential
      components and indices of the nutritional value of substitutes for human milk and
      functional products for the nutrition of infants of the first year of life. There
      are shown stages of the development of the Russian system of hygienic
      requirements for baby food, and the direction of its harmonization with
      international and European standards, particularly for substitutes for human milk
      and products of dietary therapeutic and dietary preventive nutrition for babies.
      There are considered aspects of the introduction ofproducts and weaning food
      dishes into the food ration of infants. There is presented the classification
      ofproducts of children's food and the assortment of each group of weaning foods.
      There is provided the modern legislative framework in the field of the quality
      and safety for infant nutrition. There was shown the difference between domestic
      legislation and regulatory framework of the EurAsEC Customs Union of the European
      countries in the field offood products safety for children older three years.
      There are presented proposals on the creation of the single regulatory base
      within the framework of the EurAsEC Customs Union for control the quality and
      safety of all the baby foods.

PMID- 29446273
TI  - [Hygienic substantiation of application of functional dairy products in the
      prevention of macro- and micronutrient deficiency].
AB  - Based on the study of actual nutrition and availability of macroelements there
      was found that adult population of the city of Omsk was established to refer to
      the group at risk for the development of micronutrient deficiency associated with
      low content of a set of essential elements (copper, zinc, calcium, selenium) in
      the ration, being prior for correction.There was executed the hygienic
      substantiation developed the fermented acid milk bioproduct of a functional
      purpose "Bifidin" enriched with micronutrients, prior for the population of the
      Omsk region. Introduction of this bio-product into the ration allows to
      effectively correct disorders of the mineral status, that was manifested in a
      decline in the proportion of patients with insufficiency of calcium (from 37.9 to
      24.1%; p = 0.013), copper (from 51.7 to 25.9%; p = 0.004), selenium (from 96.6 to
      84.5%; p = 0.026), zinc (from 58.6 to 48.3% of the subjects; p = 0.264). Upon the
      completion of the prophylactic course (intake "Bifidin" of 200 ml for 60 days),
      there was noted the gain in the concentration in hair: calcium (by 24.4%;
      p=0.441), zinc (by 8.0%; p=0.0008), copper (by 8.8%; p < 0.001), selenium (by
      41.5%; p < 0.001). There was established the efficacy of the use of bio-product
      "Bifidin" enriched with micronutrients for the improvement of the structure of
      nutrition and element status of the adult population of the city of Omsk. There
      was justified the extensive use of dairy products enriched with micronutrients
      both for the reduction of the prevalence of microelementoses and the improvement
      of the nutritional status.

PMID- 29446274
TI  - [The method of multicomponent determination of herbicides of various chemical
      classes in water].
AB  - In the work there are considered results of the development of the multicomponent
      method of measurement of concentration of herbicides of various chemical nature
      under their joint presence in the water. There was justified the optimality of
      application of HPLC-DAD (the working wavelength of 240 nm) for the determination
      of levels of 10 active ingredients of herbicides of class of sulfonylurea
      (metsulfuron-methyl, nikosulfuron, sulfometuron-methyl, thifensulfuron-methyl,
      triflusulfuron-methyl), imidazolinone (imazapyr, imazethapyr), 2,6-Bis[(4,6
      dimethoxy-2- pyrimidinyl)oxy]benzoic acid (bispyribac acid), triazol-pyrimidines
      (Penoxsulam), a benzoylpyrazole compound (Topramenzone). For the concentrating
      and cleaning of samples of water there were used cartridges for solid-phase
      extraction of Oasis HLB - the macro porous copolymer made on the basis of the
      balanced ratio of 2 monomers - lipophilic divinylbenzene and hydrophilic N
      vinylpirrolidone. The range of the detected concentrations in water was volatile
      between 0.0005 and 0.005 mg/L, values of standard deviation vary in the range of
      1.8-3.9%. Chlorine-containing acidic herbicides were analyzed by the method of GC
      ECD and GC-MS (IE) after preliminary converting of compounds into flying
      derivatives with the use of diazomethane. Satisfactory extraction of substances
      from a water sample may be achieved by classical extraction in the system "liquid
      liquid" with the application of Methyl tert-butyl ester. For cleaning of the
      derivatized sample there were used cartridges for solid-phase extraction on the
      basis of silica gel. The range of the determination of 9 active ingredients
      referring to classes of phenoxy-acetic acid (2,4- D, MCPA), pyridinecarboxylic
      (aminopyiralid, picloram, clopyralid), benzoic acids (dicamba),
      benzothiadiazinone (bentazone), biphenyl ester (acifluorfen) and a
      chloroacetamide (acetochlor) - 0.0001-0.001 mg/L, SD values vary in the range of
      1.8-33%.

PMID- 29446275
TI  - [Determination of polioksin B in the air environment and in washouts from skin of
      operators by HPLC].
AB  - Polyoxin B being an effective inhibitor of synthesis of chitin of the cell wall
      of many phytopathogenic fungi, is recommended as a fungicide for control of
      phytopathogenic organisms that cause damage to crop. For the determination of the
      exposure of employees working with pesticides there was developed the method of
      the measurement of concentrations of polyoxin B in air of working area,
      atmospheric air of populated areas and washouts from the operators ' integuments,
      based on high performance liquid chromatography with ultraviolet detector
      (detection wavelength of270 nm), including sampling air environment in the
      sorption tube ORBO-44, filled with sorbent XAD-2, extraction of the sorbent with
      polyoxin by a mixture of carbinol-water (in a ratio of 95:5,on volume), washout
      from the surface of the skin with ethyl alcohol by way of washing, concentrating,
      quantitative chromatographic analysis. Lower limits of the quantification
      ofpolyoxin B in the air ofworking area - 0.2 mg/m at the aspiration of 2 dm of
      air, atmospheric air - 0.016 mg/m at the aspiration of 25 dm of air, in washouts
      from the operators' integuments - 0.4 pg/wash, the linear range of the defined
      concentrations accounted for of 0.2 - 2.4 pg/cm, the total error of measurement
      of the concentrations of polyoxin B in air is 17%; in washouts from the
      operators' integuments - 16%. The developed method was approbated for the
      determination of polyoxin in samples of air of working zone, atmospheric air
      within the sanitary gap, washouts from the operators ' integuments and air drift
      samples taken under processing of roses in the hothouse and in the monitoring of
      the phytosanitary condition of the plants every other day after treatment.

PMID- 29446277
TI  - [Hygienic assessment of atmospheric air in the areas with different degrees of
      the development of the road-traffic complex].
AB  - The paper presents the results of a study of the qualitative composition and
      quantity of pollutants in atmospheric air in the course of operational wear of
      the road surface, braking system and tire treads of automobiles. On the basis of
      field research in samples ofatmospheric air ofthe city of St. Petersburg there
      were identified compounds of heavy metals andpolycyclic aromatic hydrocarbons
      (PAHs). There was established the dependence of the level of air pollution on
      traffic flows in locations of the city. Pollutants were shown to enter the air
      environment mainly in the form offine dust particles. There was justified the
      need for the control ofproducts of wear the road traffic complex in the hygienic
      assessment of the quality of ambient air ofmegalopises.

PMID- 29446276
TI  - [Determination of residual amounts of chlorothalonil in peaches: problems of gas
      chromatographic identification with the use of electron capture detector].
AB  - In the work there are presented results of studies on the validation of the gas
      chromatographic (GC) methodfor the determination of chlorothalonil residue
      amounts in peaches with the use of electron capture detector (ECD). For the
      analytical control there was selected such stone fruit crop as the peach,
      referring to the crops, the most contaminated with residue amounts ofpesticides.
      There was justified the necessity of the inclusion in the procedure of the
      detection of the method of confirmation, based on mass spectrometry detection
      (MSD) (the type of ionization - electron impact). The significant source of the
      obtaining of incorrect data in the identification with the use of ECD of ions are
      shown to be phthalates, visualized in the chromatogram as intense and/or broad
      peaks. Mass spectra of compounds of the class ofphthalates are characterized by
      the dominant peak of the ion with the value of (mass/ charge) 149, just on this
      peak the detection of low molecular weight phthalates occurs in various matrices,
      on the spectrum there are also recorded typical ions corresponding to fragments
      of radical residues. The combination of the use of various types of the detection
      allows to prove that the revealed response (detector signal) is caused just by
      the analyte, but not the impurities, and optionally to optimize chromatographic
      conditions towards to the obtaining reliable results. The lower limit of the
      quantitation of chlorothalonil in peach fruits accounts for 0.01 mg/kg,
      determined with a signal/noise ratio of 10. The range of measured concentrations
      is volatile between 0.01-0.1 mg/kg, recovery rate of chlorothalonil from samples
      of peaches, established according to results of the analysis of model samples
      with the introduction of the substance in four points along the detection range,
      was 84-102%, the SD value of the repeatability varies in the range of 2.0-5.8%.

PMID- 29446278
TI  - [Hygienic assessment of conditions of the exploitation of facilities of the urban
      drainage system].
AB  - The aim of the study was the hygienic characteristics of the location of sewage
      pumping stations (SPSs) in the residential area of the city and the assessment of
      working conditions for the staff. The features of the technological process at
      the SPSs resulted in the formation of specific working conditions characterized
      by the presence of a cooling microclimate, noise production, technological
      vibration, air pollution by microorganisms. The assessment of working conditions
      has allowed to refer them to the 3 class (harmful working conditions) of the 2
      and 3 degree. Preventive measures for SPSs should include the use of equipment
      for cleaning the air of working zone, having a combined odourremoving and
      microbicidal action; the automation of the labor process; the installation of
      additional equipment for filtering air circulating in workplaces and emitting
      into the atmosphere; provision of sealing equipment with the use of noise
      insulating materials.

PMID- 29446279
TI  - [Microbiological monitoring of opportunistic Enterobacteriaceae of the Lena
      river].
AB  - The aim is the study of the circulation, biological activity, persistent
      potential and genotypic characteristics of opportunistic Enterobacteriaceae of
      microbial community of the Lena River which is the one of the largest sources of
      water in Russia and Siberia. Gram-negative component of microbial community in
      the Lena River was mainly represented by Enterobacteriaceae (80%), including
      dominated Escherichia (dominant class) and Enterobacter and Klebsiella
      (subdominant class). In conditions of anthropogenic pollution there is a
      reorganization of microbial community of the Lena River in the direction of the
      increase in the proportion of opportunistic pathogens, their species diversity;
      there is a change of the biological activity of microorganisms, gains of share of
      strains characterized by antilysozyme activity, hemolytic activity, production
      DNase, phosphatase. The parameters of system "lysozyme-antilysozyme" are
      changing, the frequency of the occurrence of bacteria with antilysozyme activity
      is increasing. This shows the restructurization of the microbial community of
      water objects. Microorganisms of water objects in territories of anthropogenic
      pollution are characterized by multiple antibiotic resistance. The proportion of
      gram-negative opportunistic Enterobacteriaceae in microbial communities of water
      ecosystems determines the potential danger of water objects and the impact on the
      level of antibiotic resistance of bacteria. Opportunistic Enterobacteriaceae of
      microbial community of the Lena River near the city of Yakutsk are characterized
      by the presence of genetic determinants of pathogenicity (hlyA and sfaG). This is
      indicative of their potential epidemiological relevance. Microorganisms with high
      biological activity are markers of their epidemiological danger.

PMID- 29446281
TI  - [Environmental pollution with fluoride compounds and their influence on children
      health].
AB  - Data of hygienic studies of air and soil during last 20 years have confirmed
      their correlating relationship with the general morbidity and a group of
      musculoskeletal diseases in children living in cities with the technogenic
      pollution of the environment. Their bones were established to grow unevenly and
      disproportionally, in 76% of children there have been violations in the
      development and growth of bones. The results of X-ray examination of hand bones
      in children and adolescents in the Irkutsk and Shelekhov cities are presented.
      Significant differences in morbidity patterns among children and adolescents
      including an increased incidence of musculoskeletal diseases by 5.6 in children
      and by 12 in adolescents have been revealed.

PMID- 29446280
TI  - [An assessment of the immune status of the children population as a marker of
      technogenic pollution of the environment].
AB  - This article describes results of the immunological study of school-aged children
      residing in cities with different levels of the technogenic air pollution.
      Children from cities with the highest level of the technogenic pollution had a
      high number of immature neutrophils (band cells) and eosinophils. The children
      living in these ecologically unfavorable areas have presented a reduction of T
      cell antigen receptor CD3, CD4, CD8, CD20, CD16, CD95. This indicates to that
      both T-cell and B-cell immunity is suppressed. The decline of the phagocytic
      function in neutrophils indicates to the suppression of the nonspecific host
      defense mechanisms also.

PMID- 29446282
TI  - [The evaluation of immunoregulatory markers in the course of neurointoxication by
      mercury over the post-exposure period].
AB  - There was executed the examination of patients with occupational chronic mercury
      intoxication in the post-exposure period after the exposure to metallic mercury
      vapor. 47 persons with an established diagnosis of chronic mercury intoxication
      (HMI) passed the laboratory and immunological examination in the period of
      exposure to metallic mercury vapor in a production environment. The average age
      of men accounted for 49.2+/-1.2 years. The experience of work in hazardous
      working conditions amounted of 21.65+/-1.61 years (1 observation). All these same
      cases were observed in the institute clinic again after 5 years (2 observation)
      and 10 years (3 observation). A control group of healthy men consisted of 47
      cases included persons of representative both age and general work experience,
      without a professional route of contact with hazardous substances. The level of
      such cytokines as IL-1beta, IL-2, IL-4, IL-6, TNF-a, INF-y and neurotropic IgG
      class antibodies directed to proteins of the nervous tissue (NF-200, GFAP, MBP, B
      dependent Ca-channel, Glu-R, DA-R, R-GABA, Ser-R, R-Chol, DNA, B2GP) in serum
      were determined by enzyme linked immunosorbent assay. There was established the
      gain in the imbalance of inflammatory mediators and production ofneural
      antibodies in dynamics after the termination of the production in conditions of
      metallic mercury vapors. Revealed features of the regulatory relationship between
      the level of cytokines and the severity of the autoimmune process were shown to
      contribute to the maintenance and progression of neurodegenerative processes.
      There was recommended the identification of immunoregulatory markers (IL-1beta,
      IL-4, TNF-a, NF-AT to 200, GFAP, S-100) as an additional criteria for the
      diagnosis of health disorders in operating and monitoring the course of the
      progredient professional mercury intoxication.

PMID- 29446283
TI  - Adjuvant Therapy in Resected Melanoma.

PMID- 29446284
TI  - [Clinical, biochemical and allergological indices characterizing occupational
      diseases of the bronchial and pulmonary system in employees at aluminium
      production].
AB  - There are many harmful factors that possess a damaging impact on the body of
      employees at aluminum production. It leads to the development of bronchial asthma
      (BA), chronic nonobstructive bronchitis (CNB) and chronic obstructive pulmonary
      disease (COPD). The pathogenesis of these disorders, as well as sensitizing
      effect offluorine in the aluminum production is not fully understood. The purpose
      of this work was to study the characteristics of laboratory indices in patients
      with occupational diseases of the respiratory system. In workers of aluminum
      production with the diagnosis of occupational diseases of respiratory system (15
      patients with a diagnosis of asthma, 30 CNB cases, 20 COPD patients) we evaluated
      the content of total protein, total cholesterol, high density lipoprotein
      cholesterol (HDLC), total calcium, phosphorus, ceruloplasmin, hematological
      indices and performed emigration of leukocytes braking test (TTEEL). Clinical and
      biochemical profile ofpersons with occupational asthma was characterized by a low
      level of total calcium and ceruloplasmin, a high concentration of phosphorus in
      the blood serum and inhibition of leukocyte emigration in the test with sodium
      fluoride. For aluminum production CNB workers characteristic active
      proatherogenic process was pronounced by a decrease in the HDLC level and an
      increase in atherogenic index; higher hematocrit value and concentration of
      erythrocytes, and more than 50% of cases of sensitization to the presence of
      sodium fluoride. COPD cases had occupational lower average concentration of
      hemoglobin in the erythrocyte, total protein in serum, as well as polymorphic
      variant response to sodium fluoride in the form of a depression and activation of
      leucocytes emigration.

PMID- 29446285
TI  - Adjuvant Therapy in Resected Melanoma.

PMID- 29446286
TI  - [Formation of working conditions and the problems of hygienic assessment of
      industrial environmental factors in railway tunnels].
AB  - Tunnels are an integral part of the ways and artificial constructions of the
      railway. Objective assessment of working conditions is important, because current
      regulations fail to allow to give a definite hygienic assessment of some factors
      of the production environment of the tunnels. Objective: to reveal the
      peculiarities of the formation of working conditions in railway tunnels with the
      subsequent hygienic assessment for the development of preventive measures.
      Measurement of the factors of working process and working environment is carried
      out with the use of the certified equipment for the approved the hygienic and
      sanitary-chemical methods in workplaces in tunnels of the East-Siberian railway.
      Specific conditions were shown to be formed due to constructive solutions,
      climate and geographical location, the length of railway tunnels, the composition
      of the rocks through which the tunnel, the nature of the maintenance tunnels,
      ventilation system, repetition rate and type of passing rolling stock. All
      employees from occupational groups from examined tunnels were established to be
      exposed to high concentrations of aerosols with predominantly fibrogenic action,
      noise levels, adverse climate (low positive and negative temperatures, high
      relative humidity and mobility of air), the lack of natural lighting, low levels
      of artificial light, hard exertion of labor (dynamic physical load, working
      position, the slopes of the body, movement in space). Additionally, high levels
      of the vibration, nonionizing and ionizing radiation were typical for jobs of the
      Baikal and the North-Muya tunnel. There is proposed the algorithm of hygienic
      assessment of the microclimate, light environment at the working places depending
      on the time of the works in the underground conditions and constructional
      features of tunnels, methods of accounting personnel dose rates from natural
      sources.

PMID- 29446287
TI  - Adjuvant Therapy in Resected Melanoma.

PMID- 29446288
TI  - Adjuvant Therapy in Resected Melanoma.

PMID- 29446289
TI  - [The impact of harmful occupational factors on the morbidity rate of workers of
      the railway-car repair plant].
AB  - The rail transport is the one of the leading sectors of the national economy.
      More than 50% of the employees of the enterprises of the railway complex work
      under the unfavourable impact of hazardous and dangerous substances and
      occupational factors. In the literature issues of working conditions and health
      of employees of railway carrepairing plant are hardly highlighted. The aim of the
      study is the evaluation of the morbidity rate shaped under the influence of
      harmful occupational factors for the elaboration of preventive measures. In the
      work there were used generally accepted methods of hygienic studies, analysis of
      morbidity rate with temporary disability (TD), according to records of periodic
      medical examinations, occupational prevalence. The railway car-repairing plant
      was established to be characterized by the complex of harmful factors of the
      working environment and labor process: noise, local vibration, industrial
      aerosols of complex composition, chemicals, low light, hardness of the labor
      process. The levels of incidence with temporal disability in the studied groups,
      depending on the work seniority in the harmful labor conditions, significantly
      decrease with the experience from 5 to 9 years and increase with the experience
      more than 10 years. Executed in-depth analysis as of the both morbidity rate and
      TD, as well results of periodic medical examinations of workers of main shops
      shows that overall indices of the morbidity rate and TD are significantly higher
      than in the comparison group; levels of the morbidity rate and TD in the observed
      groups significantly decline depending on the length of service in hazardous
      working conditions with a length of the experience offrom 5 to 9 years and
      increase with the increase in the length of experience of 10 years or more. In
      the structure of morbidity and TD leading positions are occupied by diseases of
      the respiratory system, musculoskeletal system and connective tissue, circulatory
      system and digestive system, diseases of the eye and its appendages. The health
      damage risk coefficients in the studied groups of workers and the average losses
      of working time due to the morbidity with TD per 1 employee in all shops are
      higher than those in the comparison group. The level of the occupational
      morbidity rate is very low. Harmful working conditions contribute to the
      development of general and occupationally related diseases.

PMID- 29446290
TI  - [Hygienic assessment of toxic dust factor at the aluminium smelter in Eastern
      Siberia].
AB  - There is presented the assessment of priority toxic matters in the air of working
      zone for basic occupations of aluminum smelting by electrolysis. There are
      presented results of different production technologies. There are presented the
      results of the physical-chemical analysis of the morphology and composition of
      produced toxic-dust complexes.

PMID- 29446291
TI  - Mepolizumab for Eosinophilic COPD.

PMID- 29446292
TI  - Mepolizumab for Eosinophilic COPD.

PMID- 29446293
TI  - [The impact of the long-term exposure of industrial aerosols on clinical and
      functional indices of the broncho-pulmonary system in aluminum smelter workers].
AB  - It was found that the appearance of respiratory diseases among workers was
      established to be associated with the impact of aerosols with the complex
      chemical composition, exceeding corresponding MAC. Among respiratory diseases in
      workers there were detected predominantly chronic non-obstructive bronchitis -
      59.15%, and chronic obstructive pulmonary disease (COPD) - in 35.2% of cases. In
      the analysis of spirometric indices of examined patients the vast majority
      (76.3%) of them showed disturbances of the bronchial patency of mild to moderate
      degree of the pronouncement. As a result of the implementation offlexible
      bronchoscopy there was established the presence of a diffuse lesion of bronchi
      with a predominance of subatrophic and atrophic processes in the mucosa. It was
      found that under the increase of the concentration of HF in the air of industrial
      premises the probability of bronchial obstruction and deterioration of the
      tracheobronchial patency in aluminum smelter workers was established to elevate.

PMID- 29446294
TI  - [Assessment of carcinogenic risks to workers of the main enterprises of the
      Irkutsk region].
AB  - The purpose of research is the assessment of the individual cancer risk (ICR) for
      workers of the basic occupations in key branches of industry of the Irkutsk
      region. There was executed the calculation of ICR levels for workers of the basic
      occupations of the aircraft industry, aluminum smelters and vinyl chloride
      production plants. The estimation of the exposure for workers was carried out
      according to long-term time-weighted average concentrations in the air of the
      working area, for the population - on annual average concentrations in the
      ambient air. To assess the risk that is not associated with the profession, the
      dose was calculated for the period of life (70 years). When calculating the
      toxicant doses in the working area there were used the "standard" indices
      ofpulmonary ventilation for adults, body weight, the work experience in the
      contact with carcinogens of 30 years, the number of days in the contact of 240,
      the duration of the working time 8 or 12 hours (in accordance with the working
      hours) duration. ICR for the Irkutsk population amounted of 3.08E-04, in
      Shelekhov - 4.8E-05, Sayansk - 1.1E-05. The amount of risk depends on the content
      offormaldehyde in all territories and chromium VI in cities of Irkutsk and
      Shelekhov. ICR for workers of basic occupations of studied plants in dozens of
      times are higher than for the urban population. Priority carcinogens are:
      chromium VI, nickel, formaldehyde, silicon dioxide -for the aircraft plant
      employees; 1,2-dichloretan, vinyl chloride - for the workers of vinyl chloride
      production plant; benzopyrene - for the aluminum smelter workers.

PMID- 29446295
TI  - Diuretic Treatment in Heart Failure.

PMID- 29446296
TI  - Diuretic Treatment in Heart Failure.

PMID- 29446297
TI  - Diuretic Treatment in Heart Failure.

PMID- 29446298
TI  - [Clinical and neurophysiological peculiarities of health disorders in workers in
      dependence on the vinyl chloride exposure load].
AB  - Results of the clinical and neurophysiological examinations of 42 workers with
      operating history at the chemical plant exposed to vinyl chloride (VC) are
      presented. The purpose of research was the identification ofpeculiarities of
      clinical manifestations and disorders of the functional activity of the brain in
      workers at the vinyl chloride production, with taking into account the exposure
      toxic load (ETL). There were made clinical and electroencephalographic
      examinations with the detection of cognitive evoked potentials (CEP) and
      statistical analysis of results with the use of the Mann-Whitney U-test, Fisher's
      F-test, calculation of Spearman's correlation coefficient. The features in
      clinical picture of the pathology of the nervous system were detected in the form
      of asthenic disorders with cognitive impairment and autonomic dysfunction
      syndrome. There was established the increase in the cognitive impairment rate (p
      = 0.03), the decline in a-EEG activity (p = 0.01) and the worsening of indices of
      the amplitude (p = 0.011) and latency (p = 0,05) of CEP in extremely high level
      of ETL in comparison with same indices in the group with moderately high ETL. In
      the first group there was revealed a statistically significant exceedance of the
      frequency of hypertension - by 1.6 times, skin diseases - by 9 times, chronic
      subatrophic rhino-pharyngitis by 1.4 times in comparison with cases from the
      second group. In the group with moderately high level of ETL there was
      established the statistically significant inverse correlationship between the ETL
      and the index of P300 amplitude from the left side (r = -0.38, p = 0.019) and in
      the group with extremely high level ETL - between ETL and index of the beta2 -
      rhythm (r = - 0.73, p = 0.0008).

PMID- 29446299
TI  - Correction to "A Never-Ending Story of Per- and Polyfluoroalkyl Substances
      (PFASs)?"

PMID- 29446300
TI  - Mineralogical Evidence of Galvanic Corrosion in Drinking Water Lead Pipe Joints.
AB  - Galvanic corrosion as a mechanism of toxic lead release into drinking water has
      been under scientific debate in the U.S. for over 30 years. Visual and
      mineralogical analysis of 28 lead pipe joints, excavated after 60+ years from
      eight U.S. water utilities, provided the first direct view of three distinct
      galvanic corrosion patterns in practice: (1) no evidence of galvanic corrosion;
      (2) galvanic corrosion with lead cathode; (3) galvanic corrosion with lead anode.
      Pattern 3 is consistent with empirical galvanic series (lead -> brass -> copper
      in order of increasing nobility) and poses the greatest risk of Pb exposure.
      Pattern 2 is consistent with galvanic battery reversion. The identification of
      copper-sulfate minerals (Pattern 2), and lead-sulfate and lead-chloride minerals
      (Pattern 3) in galvanic zones illustrated the migration of chloride and sulfate
      toward the anode. Geochemical modeling confirmed the required pH drop from the
      bulk water level to at least pH 3.0-4.0 (Pattern 2) and pH < 5.5 (Pattern 3) in
      order to form these minerals. Despite joints being over 60 years old, galvanic
      zones in Pattern 3 were active and possibly posed an important source of lead to
      drinking water. Importantly, Pattern 3 was not observed in samples from systems
      representing water qualities favoring PbO2 formation.

PMID- 29446301
TI  - Plasmon Waveguiding in Nanowires.
AB  - Nanowires supporting propagating surface plasmons can function as nanowaveguides
      to realize the light guiding with field confinement beyond the diffraction limit,
      providing fundamental building blocks for nanophotonic integrated circuits. This
      review covers the recent developments of plasmon waveguiding in nanowires, mainly
      including plasmon waveguiding in metal nanowires, coupling of nanowire plasmons
      and emitters, hybrid nanowire waveguides and plasmonic gain, and nanowire
      photonic devices. We first introduce the main techniques for fabricating metal
      nanowires, the plasmon modes in metal nanowires and the excitation/detection
      methods. We then discuss the fundamental properties of plasmon propagation and
      emission, including zigzag, chiral and spin-dependent propagation, mode
      conversion, loss and propagation length, group velocity, terminal emission, and
      leaky radiation. Then the interactions between nanowires and emitters are
      reviewed, especially the coupling of single nanowires and single quantum
      emitters. Finally, we briefly introduce the hybrid nanowire waveguide composed of
      a semiconductor nanowire and a metal film with an intervening thin insulator and
      highlight a few nanophotonic devices based on plasmonic nanowire networks or
      plasmonic-photonic hybrid nanowire structures.

PMID- 29446302
TI  - Life Cycle Assessment of Connected and Automated Vehicles: Sensing and Computing
      Subsystem and Vehicle Level Effects.
AB  - Although recent studies of connected and automated vehicles (CAVs) have begun to
      explore the potential energy and greenhouse gas (GHG) emission impacts from an
      operational perspective, little is known about how the full life cycle of the
      vehicle will be impacted. We report the results of a life cycle assessment (LCA)
      of Level 4 CAV sensing and computing subsystems integrated into internal
      combustion engine vehicle (ICEV) and battery electric vehicle (BEV) platforms.
      The results indicate that CAV subsystems could increase vehicle primary energy
      use and GHG emissions by 3-20% due to increases in power consumption, weight,
      drag, and data transmission. However, when potential operational effects of CAVs
      are included (e.g., eco-driving, platooning, and intersection connectivity), the
      net result is up to a 9% reduction in energy and GHG emissions in the base case.
      Overall, this study highlights opportunities where CAVs can improve net energy
      and environmental performance.

PMID- 29446303
TI  - COMPLICATIONS OF LOWER EXTREMITY HEMATOMAS IN PATIENTS WITH PRE-INJURY WARFARINE
      USE.
AB  - INTRODUCTION: The aim of this paper is to ascertain the number of patients with
      pre-injury warfarin use who developed lower extremity hematomas treated in our
      facility, to analyse the data, used treatment methods and outcomes in these
      patients. PATIENTS AND METHODS: We performed a retrospective review, identifying
      all the patients with pre-injury Warfarin use admitted with hematoma or full
      thickness skin loss in the ten years period from January 2006 to December 2015.
      RESULTS: Overall 9 women and 2 men with mean age of 72 years were identified. All
      the injuries were sustained in a domestic setting. Except of one female patient
      primarily admitted to our department, all patients had been hospitalized
      primarily in local/regional hospitals for an average period of 32.6 days. All the
      patients transferred to our department required surgical wound closure. The mean
      wound surface area was 136.3cm2 (range 45-525). The duration of hospital stay was
      15 days in average. DISCUSSION: The data obtained were compared with the results
      and findings of similar studies and were discussed. CONCLUSION: The results
      achieved in the present study showed the beneficial effect of used treatment
      methods based on the surgical wound closure techniques during hospital stay of
      the patients. Clinicians, first contact physicians, and also patients alone need
      to be aware of the vulnerability of this group of patients. The consequences of
      even minor lower extremity trauma can be serious, with development of a very
      complex chronic wound that is difficult to manage.

PMID- 29446304
TI  - SURGICAL CORRECTION OF LABIA MINORA HYPERTROPHY, A PERSONAL TECHNIQUE.
AB  - BACKGROUND: Labia minora hypertrophy is a congenital or acquired condition in
      which both labia minora (or more rarely only one) protrude beyond the edge of the
      labia majora. The authors present a surgical technique of volumetric reduction of
      hypertrophic labia minora, associated with lipofilling of the labia majora.
      METHODS: Between 2005 and 2014, 27 patients underwent surgical reduction of labia
      minora, as described by Altier and Rouzier. The indications for surgical
      treatment varied and were as follows: interference with sexual intercourse; poor
      hygiene; difficulty wearing tight-fitting pants; difficulty while performing
      sporting activities such as cycling; aesthetic complaints. The surgical resection
      was associated with fat graft injection in labia majora in order to protect and
      cover the labia minora. The mean follow up was 1 year. RESULTS: The labia majora,
      increased in volume and firmness, cover and protect the labia minora slightly
      hypertrophic or surgically reduced. All patients reported an improvement in
      comfort, aesthetic appearance, when wearing close-fitting clothes and an
      improvement in their sexuality. In one case we recorded a "recurrence", with an
      increase of dimensions in width of labia minora, still lower than the
      preoperative situation but greater than the immediate postop. CONCLUSIONS: The
      reduction of labia minora hypertrophy with conservative techniques allows
      achieving excellent results in terms of aesthetics and functionality. The simple
      lipofilling of labia majora allows preserving and protecting the labia minora
      through a volumetric increase of the labia majora.

PMID- 29446305
TI  - SUTURE VERSUS FIBRIN GLUE MICRONEURAL ANASTOMOSIS OF THE FEMORAL NERVE IN SPRAGUE
      DEWLY RAT MODEL. A COMPARATIVE EXPERIMENTAL ASSESSMENT OF THE CLINICAL,
      HISTOLOGICAL AND STATISTICAL FEATURES.
AB  - INTRODUCTION: Peripheral nerve injury is a frequently encountered clinical
      problem that leads to functional losses at the long-term. Although microsurgical
      repair has been introduced to clinical practice in peripheral nerve injuries,
      unsatisfactory outcomes regarding functional recovery in target organ cause an
      increasing interest on studies about nerve injury and biology of the recovery in
      nerve injuries1. MATERIAL AND METHODS: Sciatic nerves of seventy adult Sprague
      Dewly rats were transected and primary anastomosis was performed. Rats were then
      divided into three groups: Control group, while 30 rats were repaired with
      sutures, and the remaining 30 were repaired with fibrin glue. After 30 days the
      rats were sacrified and the sciatic nerves were investigated histologically with
      morphometrical and statistical analyses. RESULTS: In microsurgical nerve repair,
      suture placement has been thought to cause hindrance to the sprouting axons and
      compress the blood supply to the fascicles, thereby impairing the regeneration of
      the transected nerve ends after repair, with possible neuroma formation. On the
      other hand, fibrin glue is a simple, effective technique, less time consuming
      than suturing. Another advantage of this suture-free technique is that it avoids
      injuring the axon with needles, and the lack of foreign bodies minimizes the
      inflammatory reaction. CONCLUSION: We recommend using fibrin glue as it
      demonstrates less inflammatory reaction, less scar tissue formation, it is less
      time consuming and provides better outcomes.

PMID- 29446306
TI  - INTRAOPERATIVE FAT GRAFTING INTO THE PECTORALIS AND LATISSIMUS DORSI MUSCLES
      NOVEL MODIFICATION OF AUTOLOGOUS BREAST RECONSTRUCTION WITH EXTENDED LATISSIMUS
      DORSI FLAP.
AB  - BACKGROUND: The latissimus dorsi flap is a reliable and one of the most commonly
      used methods of both immediate and delayed breast reconstruction. Its
      disadvantage is the limited volume of transferred tissue. The authors present
      their experience with the use of extended latissimus dorsi flap associated with
      immediate fat grafting into the pectoralis and latissimus dorsi muscles for
      secondary breast reconstruction. METHODS: From 2013 to 2016, 14 patients
      underwent secondary unilateral total breast reconstruction with extended
      latissimus dorsi flap associated with primary fat grafting into the pectoralis
      major and latissimus dorsi muscles. Fat was injected under visual control between
      muscle fibers. Fat injected into the pectoralis muscle formed an apparent bulging
      - autoprosthesis. RESULTS: Mean patient age was 48.2 years (range, 34 to 64
      years). Mean injected fat volume was 86.4 ml (range, 50 to 160 ml) and majority
      of this volume was injected into the pectoralis muscle. All flaps healed
      uneventfully and no fat grafting-related complications were observed. The most
      common complication was donor site seroma, which occurred in 57.1%. Results of
      postoperative ultrasound examination were evaluated. Incidence and the size of
      oil cysts and fat necroses were significantly lower in muscular layer in
      comparison with the subcutaneous layer of the reconstructed breast. CONCLUSIONS:
      Immediate fat transfer into the pectoralis and latissimus dorsi muscle increases
      the breast volume during the reconstruction with extended latissimus dorsi flap
      avoiding implant-related complications when abdominal tissue is not available.
      Pectoralis and latissimus dorsi muscles were shown as reliable and safe
      recipients for fat grafting.

PMID- 29446307
TI  - HAS A GLOMUS TUMOR ALWAYS A QUICK DIAGNOSIS?
AB  - INTRODUCTION: Glomus tumor is a rare and benign vascular tumor. Although symptoms
      specific for this tumor are quite clear, there is still a delay between the onset
      of symptoms, diagnosis and subsequent surgical therapy. The authors monitor the
      time from the onset of symptoms to the diagnosis and management of the problems.
      MATERIAL AND METHODS: Between 2004-2012, a total of 5 patients were diagnosed
      with subungual glomus tumor in the area of the distal phalanges of the hand. It
      involved 3 women and 2 men with the mean age of 32.2 years (26-47 years). During
      the first examination, we monitored the duration of symptoms, number and
      specialty of the doctors who examined the patient, and what examinations were
      performed. When the cold test was positive, MRI was performed and the patients
      were indicated for surgical revision. Tissue samples in all patients were
      histologically examined. Patients were followed for 2 years. RESULTS: It was
      found that the patients had clinical symptoms for an average of 2.4 years. In our
      group, the patients were examined by an average of 5.4 physicians (3-9
      physicians). On examination before surgery, three patients reported changes in
      the nail bed and two patients reported no change. When following the patients 2
      years after the surgery, relapse occurred in one patient and it was treated with
      reoperation. During regular follow-up 2 years after the surgery, 4 patients were
      without nail deformity. In one patient, there was resulting nail deformity.
      Relapse occurred in only one case. DISCUSSION: Because the glomus tumor is a rare
      lesion, occurring most frequently in the nail bed, early diagnosis is still a
      problem. Even in literature, we encounter a similar time frame from the onset of
      symptoms until the final diagnosis of 1.9 to 8 years. CONCLUSION: Although
      clinical signs and problems concerning the glomus tumor are very obvious, there
      still remains a long time for diagnosis. It would certainly be most beneficial
      for patients with persistent symptoms not to be referred to different
      specialists, but directly to a department that specializes in hand surgery.

PMID- 29446308
TI  - CURRENT CONCEPTS IN PERIPHERAL NERVE INJURY REPAIR.
AB  - Even though reconstructive surgery of the nerves underwent significant progress
      due to experimental and clinical research over the past 40 years, injuries to the
      peripheral nerves still remain a great challenge for microsurgery. Literature
      results of these procedures are often evaluated as very good but the final result
      is often characterized by an achievement of only a useful and not full function,
      which is rather rare. It is not only a simple suture; the success is also based
      on functional regeneration and interconnection of the nerve fibres. This is
      limited by correct surgical technique, the age of the patient, delay from the
      time of injury and the mechanism or localization of the injury. Some injuries
      even now remain untreatable (such as the most severe brachial plexus injuries or
      long traction injuries of the peroneal nerve). Apart from standard neurolysis and
      epi- or perineural suture with or without nerve grafts, distal nerve transfers
      (in case of proximal injuries) and end-to-side neurorrhaphy (mainly in trauma of
      sensitive nerves) have recently been frequently used. The future is however based
      on influence of nerve regeneration at the cellular level using substances with
      growth potential. The main prerequisite of successful surgery is however early
      indication of surgical revision in a specialized centre.

PMID- 29446309
TI  - SUBACUTE ARTERIAL BLEEDING AFTER SIMULTANEOUS MASTOPEXY AND BREAST AUGMENTATION
      WITH IMPLANTS: CASE REPORT.
AB  - Breast augmentation with implants is one of the most commonly performed plastic
      surgery procedures. The goal of the operation is to increase the size, shape or
      fullness of the breast. It is accomplished by placing silicone, saline or
      alternative composite breast implants under the chest muscles, fascia or the
      mammary gland. This type of operation is no exception with regards to concerning
      the occurrence of complications. The most common early complications include an
      infectious process, a seroma, and a hematoma, and the late ones include capsular
      contracture, reoperation, implant removal, breast asymmetry, and a rupture or
      deflation of the implant. The authors present a case of subacute arterial
      bleeding after simultaneous mastopexy and breast augmentation with silicone
      implants in a 27-year-old woman. The patient complained of worsening swelling and
      pain in the right breast. The patient denied having had any traumas.
      Ultrasonography indicated 2.5 cm heterogeneous fluid collections around the
      implant. Therefore, revision surgery was performed, and a hematoma of 650 mL was
      removed. Hemorrhage from a branch of the internal mammary artery was found. After
      the revision, the implant was returned to the lodge. The postoperative period was
      uneventful. This case report presents a description of a subacute hematoma after
      simultaneous mastopexy and breast augmentation with silicone implants, which is
      an extremely rare complication in aesthetic surgery.

PMID- 29446310
TI  - AUTOLOGOUS FAT TRANSFER, BREAST LIPOMODELLING AND FAT TRANSFER TO THE FACE:
      CURRENT GOLD STANDARDS AND EMERGING NEW DATA.
AB  - Autologous fat transfer techniques have experienced tremendous boom in the recent
      years. Plastic surgeons use these techniques to enhance both the features of the
      face and of the body. Over the years, controversies concerning fat harvesting,
      fat processing and fat injection came up. The authors of this review article
      describe their own experience with fat harvesting, processing and injection and
      show some of their own results. In addition, they discuss contemporary data from
      literature regarding the use and complications of fat grafting to the most common
      areas treated with fat grafting: breast and face.

PMID- 29446311
TI  - A practical approach to incorporating Twitter in a college course.

PMID- 29446312
TI  - Interactive laboratory classes enhance neurophysiological knowledge in Thai
      medical students.
AB  - Interactive laboratory class (ILC) is a two-way communication teaching method
      that encourages students to correlate laboratory findings with materials from
      lectures. In Thai medical education, active learning methods are uncommon. This
      paper aims to establish 1) if ILCs would effectively promote physiology learning;
      2) if effectiveness would be found in both previously academically high
      performing and low-performing students; and 3) the acceptability of ILCs to Thai
      medical students as a novel learning method. Two hundred seventy-eight second
      year medical students were recruited to this study. We conducted three ILC
      sessions, which followed corresponding lectures. We carried out multiple-choice
      pre- and post-ILC assessments of knowledge and compared by repeated-measures
      ANOVA and unpaired t-test. Subgroup analysis was performed to compare high
      performance (HighP) and low-performance (LowP) students. After the ILCs,
      participants self-rated their knowledge and satisfaction. Post-ILC test scores
      increased significantly compared with pre-ILC test scores in all three sessions.
      Mean scores of each post-ILC test increased significantly from pre-ILC test in
      both LowP and HighP groups. More students self-reported a "very high" and "high"
      level of knowledge after ILCs. Most students agreed that ILCs provided more
      discussion opportunity, motivated their learning, and made lessons more
      enjoyable. As an adjunct to lectures, ILCs can enhance knowledge in medical
      students, regardless of previous academic performance. Students perceived ILC as
      useful and acceptable. This study supports the active learning methods in
      physiology education, regardless of cultural context.

PMID- 29446313
TI  - Digital chalk-talk videos improve knowledge and satisfaction in renal physiology.
AB  - The authors began a curriculum reform project to improve the experience in a
      Renal Physiology course for first-year medical students. Taking into account both
      the variety of learning preferences among students and the benefits of student
      autonomy, the authors hypothesized that adding digital chalk-talk videos to
      lecture notes and live lectures would improve student knowledge, course
      satisfaction, and engagement. The authors measured performance on the renal
      physiology exam before (the traditional curriculum) and for 2 yr after
      implementation of the new curriculum. During the traditional and subsequent
      years, students took a Q-sort survey before and after the Renal Physiology
      course. Satisfaction was assessed based on ranked statements in the Q sort, as
      well as through qualitative analysis of student commentary. Compared with the
      traditional curriculum, mean scores on the renal physiology final exam were
      higher after implementation of the new curriculum: 65.3 vs. 74.4 ( P < 0.001)
      with year 1 and 65.3 vs. 79.4 ( P < 0.001) in the second year. After the new
      curriculum, students were more likely to agree with the statement, "I wish other
      courses were taught like this one." Qualitative analysis revealed how the video
      based curriculum improved student engagement and satisfaction. Adding digital
      chalk-talk videos to a traditional Renal Physiology course that included active
      learning led to improved exam performance and high levels of student
      satisfaction. Other preclinical courses in medical school may benefit from such
      an intervention.

PMID- 29446314
TI  - Improving physiology learning and understanding by adding outreach activities to
      the teaching: report of the IUPS and ADInstruments Teaching Workshop 2017.

PMID- 29446315
TI  - Left ventricular volume analysis as a basic tool to describe cardiac function.
AB  - The heart is often regarded as a compression pump. Therefore, determination of
      pressure and volume is essential for cardiac function analysis. Traditionally,
      ventricular performance was described in terms of the Starling curve, i.e.,
      output related to input. This view is based on two variables (namely, stroke
      volume and end-diastolic volume), often studied in the isolated (i.e.,
      denervated) heart, and has dominated the interpretation of cardiac mechanics over
      the last century. The ratio of the prevailing coordinates within that paradigm is
      termed ejection fraction (EF), which is the popular metric routinely used in the
      clinic. Here we present an insightful alternative approach while describing
      volume regulation by relating end-systolic volume (ESV) to end-diastolic volume.
      This route obviates the undesired use of metrics derived from differences or
      ratios, as employed in previous models. We illustrate basic principles concerning
      ventricular volume regulation by data obtained from intact animal experiments and
      collected in healthy humans. Special attention is given to sex-specific
      differences. The method can be applied to the dynamics of a single heart and to
      an ensemble of individuals. Group analysis allows for stratification regarding
      sex, age, medication, and additional clinically relevant covariates. A
      straightforward procedure derives the relationship between EF and ESV and
      describes myocardial oxygen consumption in terms of ESV. This representation
      enhances insight and reduces the impact of the metric EF, in favor of the end
      systolic elastance concept advanced 4 decades ago.

PMID- 29446316
TI  - Impact of the INBRE summer student mentored research program on undergraduate
      students in Arkansas.
AB  - The Institutional Development Award (IDeA) program, housed within the National
      Institute for General Medical Sciences, administers the Networks of Biomedical
      Research Excellence (INBRE) as a strategic mission to broaden the geographic
      distribution of National Institutes of Health (NIH) funding within the United
      States. Undergraduate summer student mentored research programs (SSMRP) are a
      common feature of INBRE programs and are designed to increase undergraduate
      student interest in research careers in the biomedical sciences. Little
      information is available about student perspectives on how these programs impact
      their choices relative to education and careers. Therefore, we conducted
      qualitative interviews with 20 participants from the Arkansas INBRE SSMRP in the
      years 2002-2012. Each telephone interview lasted 30-45 min. An interview guide
      with a broad "grand tour" question was used to elicit student perspectives on
      SSMRP participation. Interviews were digitally recorded, then transcribed
      verbatim, and the transcript checked for accuracy. Content analysis and constant
      comparison were used to identify nine themes that were grouped into three
      temporal categories: before, during, and after the SSMRP experience. Students
      viewed the experience as positive and felt it impacted their career choices. They
      emphasized the value of mentoring in the program, and some reported maintaining a
      relationship with the mentor after the summer experience ended. Students also
      valued learning new laboratory and presentation skills and felt their research
      experience was enhanced by meeting students and scientists with a wide range of
      career interests. These data suggest that the Arkansas INBRE and the NIH IDeA
      program are successfully meeting the goal of increasing interest in research
      among undergraduates.

PMID- 29446318
TI  - Cardiovascular Risk Factors in Airline Pilots.
AB  - The health of an airline pilot is imperative to the safe travels of millions of
      people worldwide. Medical providers evaluate the cardiovascular risks for airline
      pilots and the medical requirements to obtain and maintain licensure as an
      airline pilot. It is the role of the occupational health nurse practitioner to
      evaluate and reduce the risk of cardiovascular disease in this population.

PMID- 29446317
TI  - Credentialing of radiotherapy centres in Australasia for TROG 09.02 (Chisel), a
      Phase III clinical trial on stereotactic ablative body radiotherapy of early
      stage lung cancer.
AB  - OBJECTIVE: A randomised clinical trial comparing stereotactic ablative body
      radiotherapy (SABR) with conventional radiotherapy for early stage lung cancer
      has been conducted in Australia and New Zealand under the auspices of the
      TransTasman Radiation Oncology Group (NCT01014130). We report on the technical
      credentialing program as prerequisite for centres joining the trial. METHODS:
      Participating centres were asked to develop treatment plans for two test cases to
      assess their ability to create plans according to protocol. Dose delivery in the
      presence of inhomogeneity and motion was assessed during a site visit using a
      phantom with moving inserts. RESULTS: Site visits for the trial were conducted in
      16 Australian and 3 New Zealand radiotherapy facilities. The tests with low
      density inhomogeneities confirmed shortcomings of the AAA algorithm for dose
      calculation. Dose was assessed for a typical treatment delivery including at
      least one non-coplanar beam in a stationary and moving phantom. This end-to-end
      test confirmed that all participating centres were able to deliver stereotactic
      ablative body radiotherapy with the required accuracy while the planning study
      demonstrated that they were able to produce acceptable plans for both test cases.
      CONCLUSION: The credentialing process documented that participating centres were
      able to deliver dose as required in the trial protocol. It also gave an
      opportunity to provide education about the trial and discuss technical issues
      such as four-dimensional CT, small field dosimetry and patient immobilisation
      with staff in participating centres. Advances in knowledge: Credentialing is an
      important quality assurance tool for radiotherapy trials using advanced
      technology. In addition to confirming technical competence, it provides an
      opportunity for education and discussion about the trial.

PMID- 29446319
TI  - Dual-energy CT iodine maps as an alternative quantitative imaging biomarker to
      abdominal CT perfusion: determination of appropriate trigger delays for
      acquisition using bolus tracking.
AB  - OBJECTIVE: Quantitative evaluation of different bolus tracking trigger delays for
      acquisition of dual energy (DE) CT iodine maps as an alternative to CT perfusion.
      METHODS: Prior to this retrospective analysis of prospectively acquired data,
      DECT perfusion sequences were dynamically acquired in 22 patients with pancreatic
      carcinoma using dual source CT at 80/140 kVp with tin filtration. After
      deformable motion-correction, perfusion maps of blood flow (BF) were calculated
      from 80 kVp image series of DECT, and iodine maps were calculated for each of the
      34 DECT acquisitions per patient. BF and iodine concentrations were measured in
      healthy pancreatic tissue and carcinoma. To evaluate potential DECT acquisition
      triggered by bolus tracking, measured iodine concentrations from the 34 DECT
      acquisitions per patient corresponding to different trigger delays were assessed
      for correlation to BF and intergroup differences between tissue types depending
      on acquisition time. RESULTS: Average BF measured in healthy pancreatic tissue
      and carcinoma was 87.6 +/- 28.4 and 38.6 +/- 22.2 ml/100 ml min-1, respectively.
      Correlation between iodine concentrations and BF was statistically significant
      for bolus tracking with trigger delay greater than 0 s (rmax = 0.89; p < 0.05).
      Differences in iodine concentrations between healthy pancreatic tissue and
      carcinoma were statistically significant for DECT acquisitions corresponding to
      trigger delays of 15-21 s (p < 0.05). CONCLUSION: An acquisition window between
      15 and 21 s after exceeding bolus tracking threshold shows promising results for
      acquisition of DECT iodine maps as an alternative to CT perfusion measurements of
      BF. Advances in knowledge: After clinical validation, DECT iodine maps of
      pancreas acquired using bolus tracking with appropriate trigger delay as
      determined in this study could offer an alternative quantitative imaging
      biomarker providing functional information for tumor assessment at reduced
      patient radiation exposure compared to CT perfusion measurements of BF.

PMID- 29446320
TI  - Inhibition of mucin secretion via glucocorticoid-induced regulation of calcium
      related proteins in mouse lung.
AB  - Calcium is important for physiological functioning in many tissues and is
      essential in mucus secretion and muscle contraction. Intracellular concentrations
      of calcium are regulated by calcium-related proteins, such as transient receptor
      potential cation channel subfamily V member 4 (TRPV 4), TRPV6, Calbindin-D9k
      (CaBP-9k), sodium-calcium exchanger (NCX1), and plasma membrane Ca2+ ATPase 1
      (PMCA1). In this study, the relationship between secretion of pulmonary mucus and
      calcium regulation was investigated. To confirm the effect of steroid hormones,
      immature mice were injected with estrogen (E2) or progesterone (P4), and mature
      mice were injected with dexamethasone (DEX). Subsequently, the location and
      expression of TRPV4, TRPV6, CaBP-9k, NCX1, and PMCA1 in lung tissue were
      examined. Periodic acid-Schiff staining was performed to investigate functional
      aspects of the protein expression. There were no significant differences in
      calcium-related gene expression in E2- and P4-treated mice, but TRPV4, NCX1, and
      PMCA1 were increased in DEX-treated mice and were recovered by RU486 treatment.
      DEX induces the expression of calcium-related proteins through the glucocorticoid
      receptor-mediated pathway and may involve decreased mucin secretion in the
      bronchiole. TRPV4, TRPV6, CaBP-9k, NCX1, and PMCA1 were specifically expressed in
      Clara and alveolar type 2 cells of mouse lung. CC10, a marker of Clara cells, was
      decreased by DEX. In addition, mucin secretion, which is a functional aspect of
      this cell, was also decreased by DEX treatment. Control of calcium-related gene
      expression may affect the control of mucus secretion in the lung. Such a control
      mechanism can form the basis of studies into diseases such as inflammation
      attributable to mucus secretion abnormalities, coughing, and respiratory
      disorders and distress.

PMID- 29446321
TI  - Pulmonary IL-1beta expression in early life causes permanent changes in lung
      structure and function in adulthood.
AB  - Chorioamnionitis, mechanical ventilation, oxygen therapy, and postnatal infection
      promote inflammation in the newborn lung. The long-term consequences of pulmonary
      inflammation during infancy have not been well characterized. The aim of this
      study was to examine the impact of inflammation during the late saccular to
      alveolar stages of lung development on lung structure and function in adulthood.
      To induce IL-1beta expression in the pulmonary epithelium of mice with a
      tetracycline-inducible human IL-1beta transgene, doxycycline was administered via
      intraperitoneal injections to bitransgenic pups and their littermate controls on
      postnatal days (PN) 0, 0.5, and 1. Lung structure, inflammation, and airway
      reactivity were studied in adulthood. IL-1beta production in early life resulted
      in increased numbers of macrophages and neutrophils on PN21, but inflammation
      subsided by PN42. Permanent changes in alveolar structure, i.e., larger alveoli
      and thicker alveolar walls, were present from PN21 to PN84. Lack of alveolar
      septation thus persisted after IL-1beta production and inflammation had ceased.
      Early IL-1beta production caused goblet cell hyperplasia, enhanced calcium
      activated chloride channel 3 (CLCA3) protein expression, and increased airway
      reactivity in response to methacholine on PN42. Lymphoid follicles were present
      adjacent to small airways in the lungs of adult bitransgenic mice, and levels of
      the B cell chemoattractant CXC-motif ligand (CXCL) 13 were elevated in the lungs
      of bitransgenic mice compared with controls. In conclusion, IL-1beta-induced
      pulmonary inflammation in early life causes a chronic lung disease in adulthood.

PMID- 29446323
TI  - Conners 3-Self-Report Scale: An empirical support to the dimensionality of the
      content scales.
AB  - The Conners' Rating Scales are one of the most used instruments for attention
      deficit/hyperactivity disorder (ADHD). Nonetheless, in the latest edition, the
      Inattention scale was not statistically supported. This study examined the
      dimensionality of the Italian version of the Conners 3-Self-Report scale testing
      both a five-factor structure including Inattention and a four-factor model
      combining Inattention and Learning Problems. Moreover, the generalizability of
      the detected structure through measurement invariance was verified. The Italian
      version of the scale was completed by 971 children (53% males, mean age: 12.76
      years) randomly split in a calibration sample ( n = 464) and a validation sample
      ( n = 507). Confirmatory factor analyses detected a five-factor structure (i.e.
      Inattention, Hyperactivity/Impulsivity, Learning Problems, Defiance/Aggression,
      and Family Relations), and measurement invariance was confirmed. Findings
      provided statistical evidence for the Inattention subscale, supporting the
      Conners 3-Self-Report Scale as effectively aimed to assess the two dimensions of
      ADHD and its main comorbid difficulties.

PMID- 29446322
TI  - BOLD MRI to evaluate early development of renal injury in a rat model of
      diabetes.
AB  - Objective To investigate changes in renal oxygenation levels by blood-oxygenation
      level dependent (BOLD)-magnetic resonance imaging (MRI), and to evaluate BOLD-MRI
      for detecting early diabetic renal injury. Methods Seventy-five rats, with
      unilateral nephrectomy, were randomly divided into streptozotocin-induced
      diabetes mellitus (DM, n = 65) and normal control (NC, n = 10) groups. BOLD-MRI
      scans were performed at baseline (both groups) and at 3, 7, 14, 21, 28, 35, 42,
      49, 56, 63 and 70 days (DM only). Renal cortical (C) and medullary (M) R2*
      signals were measured and R2* medulla/cortex ratio (MCR) was calculated. Results
      DM-group CR2* and MR2* values were significantly higher than NC values following
      diabetes induction. R2* values increased gradually and peaked at day 35 (CR2*,
      33.95 +/- 0.34 s-1; MR2*, 43.79 +/- 1.46 s-1), then dropped gradually (CR2*,
      33.17 +/- 0.69 s-1; MR2*, 41.61 +/- 0.95 s-1 at day 70). DM-group MCR rose
      gradually from 1.12 to 1.32 at day 42, then decreased to 1.25 by day 70.
      Conclusions BOLD-MRI can be used to non-invasively evaluate renal hypoxia and
      early diabetic renal injury in diabetic rats. MCR may be adopted to reflect
      dynamic changes in renal hypoxia.

PMID- 29446325
TI  - Behaviour change techniques in physical activity interventions for men with
      prostate cancer: A systematic review.
AB  - Physical activity interventions can improve prostate cancer survivors' health.
      Determining the behaviour change techniques used in physical activity
      interventions can help elucidate the mechanisms by which an intervention
      successfully changes behaviour. The purpose of this systematic review was to
      identify and evaluate behaviour change techniques in physical activity
      interventions for prostate cancer survivors. A total of 7 databases were searched
      and 15 studies were retained. The studies included a mean 6.87 behaviour change
      techniques (range = 3-10), and similar behaviour change techniques were
      implemented in all studies. Consideration of how behaviour change techniques are
      implemented may help identify how behaviour change techniques enhance physical
      activity interventions for prostate cancer survivors.

PMID- 29446324
TI  - Hepatocellular carcinoma surveillance with ultrasound-cost-effectiveness, high
      risk populations, uptake.
AB  - Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the
      second cause of cancer-related deaths worldwide. In most cases, it is diagnosed
      in patients with identified risk factors, mainly cirrhosis from all causes. These
      patients are candidates for a surveillance program that, depending on guidelines,
      involves regular liver ultrasound alone or combined with serum markers. These
      programs have been shown to improve the oncological outcome by detecting earlier
      stage tumors and providing patients with potentially curative treatment and
      improved survival. Yet, the level of evidence supporting these guidelines remains
      limited. This review article presents an overview of the evidence supporting
      surveillance programs for hepatocellular carcinoma, in particular the efficacy,
      cost-effectiveness, and consequences of this approach for patient survival.
      Western and Eastern guideline recommendations are described and discussed.

PMID- 29446327
TI  - Changes in Life Expectancy From 2006 to 2015 in Suzhou, East China: Contributions
      of Age- and Cause-Specific Mortality.
AB  - This study was designed to estimate the contribution of age- and disease-specific
      mortality, particularly that attributable to chronic noncommunicable diseases and
      at-birth life expectancy (LE) in Suzhou, East China, between 2006 and 2015. In
      total, data on 427 290 deaths were analyzed. From 2006 to 2015, the at-birth LE
      increased from 78.92 years to 82.87 years in Suzhou. A decrease in all-cause age
      specific death rates contributed to an increase of 1.98 years. The decreased
      death rates attributable to noncommunicable diseases including cerebrovascular
      diseases, cancer, heart disease, and respiratory diseases resulted in an
      increased LE of 1.37 years, which was particularly pronounced among people aged
      65 years and older. However, the prevalence of cancer in those aged 45 to 74
      years, particularly gastric, liver, and esophageal cancers, contributed the most
      to the increase in LE. These data may be useful for public health communications.

PMID- 29446328
TI  - Contribution of EEG signals to brain-machine interfaces.

PMID- 29446329
TI  - Response to "Contribution of EEG signals to brain-machine interfaces".

PMID- 29446330
TI  - Effectiveness in Regular Practice of Collaborative Care for Depression Among
      Adolescents: A Retrospective Cohort Study.
AB  - OBJECTIVE: Depression is common among adolescents, but many lack ready access to
      mental health services. Integrated models of care for depression are needed,
      along with evidence to support their use in regular practice. The authors
      examined the effectiveness of an ongoing collaborative care program for depressed
      adolescents embedded in a busy primary care practice. METHODS: This retrospective
      cohort study assessed EMERALD (Early Management and Evidence-based Recognition of
      Adolescents Living with Depression), a collaborative care program. All patients
      ages 12-17 and age 18 and still in high school with a score of >=10 on the nine
      item Patient Health Questionnaire for Adolescents (PHQ-9A) and without a
      diagnosis of bipolar disorder were eligible. The sample included 162 EMERALD
      participants and 499 similarly eligible non-EMERALD patients. Outcomes were six
      month remission of depression (score <5) and six-month treatment response (>50%
      reduction from baseline) as measured by the PHQ-9A. Analyses included logistic
      regression and propensity score matching to adjust for differences in demographic
      factors and number of contacts-observations. RESULTS: After propensity score
      matching, EMERALD patients had better adjusted rates of depression remission (11
      percentage points higher, p=.035) and treatment response (14 percentage points
      higher, p<.001) than comparison patients. Results from primary analyses were as
      conservative as or more conservative than results from all sensitivity analyses
      tested. CONCLUSIONS: Collaborative care for adolescents in regular practice led
      to better remission and treatment response than usual care. Future studies could
      examine which groups might benefit most and flexible payment models to support
      these services.

PMID- 29446331
TI  - The Case for Severe Mental Illness as a Disparities Category.
AB  - Extensive evidence documents that people with severe mental illness have higher
      rates of morbidity and mortality compared with the general population and receive
      lower-quality and higher-cost health care. These trends, at least in part, stem
      from discrimination, exclusion, widespread stigma, and criminalization of
      individuals with mental illness. As such, severe mental illness should receive
      formal, national recognition as a disparities category. Such a designation would
      have multiple important implications in health policy, services and quality
      research, and advocacy.

PMID- 29446333
TI  - Delays in Seeking General Medical Services and Measurable Abnormalities Among
      Individuals With Serious Mental Illness.
AB  - OBJECTIVE: The study explored the association of delays in seeking general
      medical care with elevated blood pressure and metabolic abnormalities among
      individuals with serious mental illness. METHODS: Association of delays in
      medical care with blood pressure, serum hemoglobin A1c (HbA1C), and lipids was
      assessed among patients at two inner-city community mental health centers.
      RESULTS: Of 271 participants, 62% reported delays in seeking general medical care
      due to attitudinal and financial barriers. Care delay was associated with
      abnormalities in measured blood pressure (adjusted odds ratio [AOR]=2.14, p=.029)
      and HbA1c (AOR=3.18, p=.026). Care delay was not associated with abnormalities in
      lipid profiles. CONCLUSIONS: This study found that delays in seeking general
      medical care are common and are associated with clinical markers linked with
      common medical conditions. The results may help to explain the elevated morbidity
      and mortality associated with serious mental illness.

PMID- 29446332
TI  - General Medical, Mental Health, and Demographic Risk Factors Associated With
      Suicide by Firearm Compared With Other Means.
AB  - OBJECTIVE: Mitigation of suicide risk by reducing access to lethal means, such as
      firearms and potentially lethal medications, is a highly recommended practice. To
      better understand groups of patients at risk of suicide in medical settings, the
      authors compared demographic and clinical risk factors between patients who died
      by suicide by using firearms or other means with matched patients who did not die
      by suicide (control group). METHODS: In a case-control study in 2016 from eight
      health care systems within the Mental Health Research Network, 2,674 suicide
      cases from 2010-2013 were matched to a control group (N=267,400). The association
      between suicide by firearm or other means and medical record information on
      demographic characteristics, general medical disorders, and mental disorders was
      assessed. RESULTS: The odds of having a mental disorder were higher among cases
      of suicide involving a method other than a firearm. Fourteen general medical
      disorders were associated with statistically significant (p<.001) greater odds of
      suicide by firearm, including traumatic brain injury (TBI) (odds ratio
      [OR]=23.53), epilepsy (OR=3.17), psychogenic pain (OR=2.82), migraine (OR=2.35),
      and stroke (OR=2.20). Fifteen general medical disorders were associated with
      statistically significant (p<.001) greater odds of suicide by other means, with
      particularly high odds for TBI (OR=7.74), epilepsy (OR=3.28), HIV/AIDS (OR=6.03),
      and migraine (OR=3.17). CONCLUSIONS: Medical providers should consider targeting
      suicide risk screening for patients with any mental disorder, TBI, epilepsy, HIV,
      psychogenic pain, stroke, and migraine. When suicide risk is detected, counseling
      on reducing access to lethal means should include both firearms and other means
      for at-risk groups.

PMID- 29446334
TI  - Leveraging Behavioral Health Expertise: Practices and Potential of the Project
      ECHO Approach to Virtually Integrating Care in Underserved Areas.
AB  - This column describes Project ECHO (Extension for Community Healthcare Outcomes),
      a teleconsultation, tele-education, telementoring model for enhancing primary
      care treatment of underserved patients with complex medical conditions. Numerous
      centers have adapted ECHO to support primary care treatment of behavioral health
      disorders. Preliminary evidence for behavioral health ECHO programs suggests
      positive impacts on providers, treatment planning, and emergency department
      costs. ECHO has the potential to improve access to effective and cost-effective
      behavioral health care by virtually integrating behavioral health knowledge and
      support in sites where specialty providers are not available. Patient-level
      outcomes research is critical.

PMID- 29446335
TI  - Implementing Illness Management and Recovery Within Assertive Community
      Treatment: A Pilot Trial of Feasibility and Effectiveness.
AB  - OBJECTIVE: In a pilot feasibility and effectiveness study, illness management and
      recovery (IMR), a curriculum-based program to help people with serious mental
      illness pursue personal recovery goals, was integrated into assertive community
      treatment (ACT) to improve participants' recovery and functioning. METHODS: A
      small-scale cluster randomized controlled design was used to test implementation
      of IMR within ACT teams in two states. Eight high-fidelity ACT teams were
      assigned to provide IMR (ACT+IMR; four teams) or standard ACT services (ACT only;
      four teams). Clinical outcomes from 101 individuals with schizophrenia-spectrum
      or bipolar disorders were assessed at baseline, six months, and one year.
      RESULTS: Exposure to IMR (session attendance and module completion) varied
      between the ACT+IMR teams, with participants on one team having significantly
      less exposure. Results from intent-to-treat analyses showed that participants in
      ACT+IMR demonstrated significantly better outcomes with a medium effect size at
      follow-up on clinician-rated illness self-management. A nonsignificant, medium
      effect size was found for one measure of functioning, and small effect sizes were
      observed for client-rated illness self-management and community integration.
      Session and module completion predicted better outcomes on four of the 12-month
      outcome measures. CONCLUSIONS: Findings support the feasibility of implementing
      IMR within ACT teams. Although there were few significant findings, effect sizes
      on some variables in this small-scale study and the dose-response relationships
      within ACT+IMR teams suggest this novel approach could be promising for improving
      recovery for people with serious mental illness. Further large-scale studies
      utilizing a hybrid effectiveness-implementation design could provide a promising
      direction in this area.

PMID- 29446336
TI  - Using Telehealth to Implement Cognitive-Behavioral Therapy.
AB  - Behavioral health issues are common among patients with comorbid medical
      conditions but often go unrecognized or untreated, resulting in worse clinical
      outcomes and avoidable medical expenditures. This column describes an innovative
      telehealth solution that includes proactive and targeted patient identification
      and engagement and nationwide delivery of a technology-enabled, standardized, and
      evidence-based behavioral health program delivered via phone or video. A
      retrospective before-after evaluation of the program demonstrated national reach,
      high patient satisfaction, and significant reductions in symptoms of depression,
      anxiety, and stress.

PMID- 29446337
TI  - A Hierarchical Framework for Evaluation and Informed Decision Making Regarding
      Smartphone Apps for Clinical Care.
AB  - With thousands of smartphone apps targeting mental health, it is difficult to
      ignore the rapidly expanding use of apps in the treatment of psychiatric
      disorders. Patients with psychiatric conditions are interested in mental health
      apps and have begun to use them. That does not mean that clinicians must support,
      endorse, or even adopt the use of apps, but they should be prepared to answer
      patients' questions about apps and facilitate shared decision making around app
      use. This column describes an evaluation framework designed by the American
      Psychiatric Association to guide informed decision making around the use of
      smartphone apps in clinical care.

PMID- 29446339
TI  - The rs1527483, but not rs3212018, CD36 polymorphism associates with linoleic acid
      detection and obesity in Czech young adults.
AB  - Recent evidence has raised the possibility of the existence of a sixth taste
      modality - that is, taste for fat - which is mediated by lingual CD36 and plays a
      role in obesity. Consequently, the genetic polymorphism of CD36 has been shown to
      be associated with altered oro-sensory detection of dietary lipids. In the
      present study, we investigated the relationship between oro-sensory perception of
      linoleic acid (LA), two CD36 polymorphisms (rs1527483 and rs3212018), obesity
      parameters and craving habits for dietary lipids in young Czech adults. We also
      sequenced 5 and 6 exons of CD36 to trace out any new mutation that might be
      responsible for the difference in taste perception. We observed that craving for
      dietary lipids was correlated with anthropometric parameters (P<0.05) and LA
      detection threshold (P=0.033). The participants with the CC genotype of the
      rs1527483 polymorphism had lower BMI (P=0.011), waist circumference (P=0.005),
      waist:height ratio (P=0.010) and higher sensitivity for LA (P=0.037) than the
      participants with the CT and TT genotypes. Interestingly, we did not observe any
      association between the rs3212018 polymorphism and the studied parameters.
      Moreover, we did not observe any mutation in exons 5 and 6 of the CD36 gene in
      these subjects. Finally, we can state that rs1527483, but not rs3212018, is
      associated with high body weight in young Czech subjects.

PMID- 29446340
TI  - Identification of vitamin B12 deficiency in vegetarian Indians.
AB  - The prevalence of a sub-clinical vitamin B12 deficiency in the vegetarians is
      high. Total serum vitamin B12 concentration alone does not reliably reflect
      vitamin B12 status. Holotranscobalamin (holo-TC) II is a bioactive B12 fraction
      promoting specific uptake of B12 by cells and the circulating concentration
      reflects the intake of B12, whereas total homocysteine (tHcy) indicates the
      metabolic ability. In this study, we investigated the diagnostic value of
      circulating holo-TC, B12, folate and homocysteine in vegetarians who were at risk
      of B12 deficiency. B12-related biomarkers were measured in 119 young, healthy
      graduate vegetarians. None was folate deficient. As per reported definition, half
      were B12 deficient; 70 % of males and 50 % of females had low plasma holo-TC
      concentrations; and 92 % of males and half of females had hyperhomocysteinaemia.
      None had any clinical signs of B12 deficiency. Receiver operating characteristic
      curve analysis demonstrated similar AUC at the B12 concentration of 100 and 150
      pmol/l when holo-TC (0.777 and 0.784) and homocysteine (0.924 and 0.928) were
      used as variables. Cut-off value of 100 pmol/l resulted in the highest
      sensitivity of 77.78 % and specificity of 71.05 % with a predictive value of 19.6
      pmol/l for holo-TC and a sensitivity of 82.72 % and specificity of 89.7 % with a
      predictive value of 21.7 umol/l for homocysteine. The combination of B12, holo-TC
      and tHcy improves the diagnostic accuracy at these cut-offs, and we suggest that
      for the young Indian vegetarians the cut-off for plasma B12 and holotrancobalamin
      is 100 pmol/l and 19.6 pmol/l, respectively, and for homocysteine it is 17.6
      (females) and 27 umol/l (males) for identifying B12 deficiency.

PMID- 29446341
TI  - Emergency Management and Preparedness Training for Youth (EMPTY): The Results of
      the First Swedish Pilot Study.
AB  - OBJECTIVE: To examine the impact of a simulation training in raising a group of
      young students' personal and situational awareness in disasters and emergencies.
      METHODS: In total, 25 young students participated in two simulation scenarios
      representing two actual events, fire, and shooting, using a combination of two
      validated simulation training (Emergency Management and Preparedness Training for
      Youth [EMPTY]). The changes in their knowledge and awareness were evaluated by
      using questionnaires and the whole simulation was evaluated by three independent
      observers and a reference group. RESULTS: New concepts of emergency management,
      for example, evacuation, and barricading, could be trained in a safe environment.
      There was a significant increase in students' personal and situational awareness
      and their active engagement in the management of emergencies. CONCLUSION: EMPTY
      could raise the youth basic knowledge and ability to understand the concept of
      preparedness by being mentally prepared, available for collaboration, gaining a
      higher confidence, understanding the physical and psychological consequences of a
      major incident and the importance of their own safety. (Disaster Med Public
      Health Preparedness. 2018; page 1 of 4).

PMID- 29446342
TI  - Effects of oral supplementation with Spirulina and Chlorella on growth and
      digestive health in piglets around weaning.
AB  - Weaning of piglets is associated with important changes in gut structure and
      function resulting from stressful events such as separation from the sow, moving
      to a new facility and dietary transition from a liquid to a solid feed. This may
      result in post-weaning diarrhoea and a decrease in feed intake and growth. In
      humans, the cyanobacterium Spirulina platensis (SP) and the freshwater microalga
      Chlorella vulgaris (CV) are known for their beneficial health effects. This study
      aimed to determine the effects of early oral administration of Spirulina and
      Chlorella in piglets on mucosal architecture and cytokine expression in the
      intestine around weaning, and consequences on growth performance and diarrhoea
      incidence. The experiment was conducted on 108 suckling piglets of 14 days of age
      (initial BW=4.9+/-0.7 kg) and weaned at 28 days of age (day 0). Animals received
      orally 385 mg/kg BW per day of SP or CV, or water (negative control (NC)) during
      4 weeks from day -14 to day 14 and their growth performance was measured daily.
      After weaning, growth, feed intake and diarrhoea incidence were measured daily.
      Intestinal morphology and functionality were assessed at day -1, day 2, and day
      14. During the suckling period, average daily gain (ADG) in SP piglets was
      higher, resulting in a higher weaning BW compared to NC and CV piglets (P0.10).
      Shorter ileal villi were measured in SP and CV piglets than in NC piglets
      (P<0.05). Cytokine expression did not differ between treatments in response to
      weaning. At day 14, IL-8 expression in the ileum was higher in SP piglets, while
      IL-1beta expression in the jejunum was higher in CV piglets (P<0.05). This study
      shows that Spirulina administration around weaning alleviates diarrhoea in weaned
      piglets, without marked modulation of local inflammation.

PMID- 29446344
TI  - Genotype characterization of livestock and human cystic echinococcosis in
      Mazandaran province, Iran.
AB  - Echinococcus granulosus is a helminth from the family Taeniidae, which causes
      cystic echinococcosis (CE) in humans and diverse livestock around the world. The
      identification of existing genotypes in different regions is a major step towards
      the prevention and establishment of control programmes for the disease. This
      study aimed to detect CE genotypes using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) of the internal transcribed spacer-1
      (ITS1) gene and sequencing of the cytochrome c oxidase subunit 1 (Cox1) gene in
      isolates from the central part of Mazandaran province, northern Iran. Forty
      isolates were collected from sheep, 17 from cattle and 6 from human formalin
      fixed paraffin-embedded tissues (FFPE). The ITS1 and Cox1 genes were successfully
      amplified by PCR in 41 and 42 samples, respectively. PCR-RFLP and sequencing
      showed that all isolates had the G1-G3 genotypes in this study. Out of 31
      isolates subjected to sequencing for the Cox1 gene, 80.7% had the G1 genotype. G2
      (16.1%) and G3 (3.2%) genotypes were observed in five sheep and one cattle
      samples, respectively. Five human isolates were also sequenced for the ITS1 gene,
      which showed that all samples belonged to the G1 genotype. Ten haplotypes were
      determined among the isolates by alignment analysis of the Cox1 gene. In summary,
      this study demonstrated that G1 was the dominant genotype circulating between
      humans and livestock in the studied region. Furthermore, high genotypic diversity
      among the CE isolates was observed.

PMID- 29446345
TI  - Phase transition of intermetallic TbPt at high temperature and high pressure.
AB  - Here we present synchrotron-based x-ray diffraction experiments combined with
      diamond anvil cell and laser heating techniques on the intermetallic rare earth
      compound TbPt (Pnma and Z  =  4) up to 32.5 GPa and ~1800 K. The lattice
      parameters of TbPt exhibit continuous compression behavior up to 18.2 GPa without
      any evidence of phase transformation. Pressure-volume data were fitted to a third
      order Birch-Murnaghan equation of state with V 0  =  175.5(2) A3, [Formula: see
      text]  =  110(5) GPa and [Formula: see text]  =  3.8(7). TbPt exhibits
      anisotropic compression with beta a   >  beta b   >  beta c and the ratio of
      axial compressibility is 2.50:1.26:1.00. A new monoclinic phase of TbPt assigned
      to the Pc or P2/c space group was observed at 32.5 GPa after laser heating at
      ~1800 K. This new phase is stable at high pressure and presented a quenchable
      property on decompression to ambient conditions. The pressure-volume relationship
      is well described by the second-order Birch-Murnaghan equation of state, which
      yields V 0  =  672(4) A3, [Formula: see text]  =  123(6) GPa, which is about ~14%
      more compressible than the orthorhombic TbPt. Our results provide more
      information on the structure and elastic property view, and thus a better
      understanding of the physical properties related to magnetic structure in some
      intermetallic rare earth alloys.

PMID- 29446343
TI  - Cost-utility analysis of antiviral use under pandemic influenza using a novel
      approach - linking pharmacology, epidemiology and heath economics.
AB  - Simulation models are used widely in pharmacology, epidemiology and health
      economics (HEs). However, there have been no attempts to incorporate models from
      these disciplines into a single integrated model. Accordingly, we explored this
      linkage to evaluate the epidemiological and economic impact of oseltamivir dose
      optimisation in supporting pandemic influenza planning in the USA. An HE decision
      analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic
      transmission model simulating the impact of pandemic influenza with low virulence
      and low transmissibility and, high virulence and high transmissibility. The cost
      utility analysis was from the payer and societal perspectives, comparing
      oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time
      horizon. Model parameters were derived from published studies. Outcomes were
      measured as cost per quality-adjusted life year (QALY) gained. Sensitivity
      analyses were performed to examine the integrated model's robustness. Under both
      pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg
      BID led to a significant reduction of influenza episodes and influenza-related
      deaths, translating to substantial savings of QALYs. Overall drug costs were
      offset by the reduction of both direct and indirect costs, making these two
      interventions cost-saving from both perspectives. The results were sensitive to
      the proportion of inpatient presentation at the emergency visit and patients'
      quality of life. Integrating PK/PD-EPI/HE models is achievable. Whilst further
      refinement of this novel linkage model to more closely mimic the reality is
      needed, the current study has generated useful insights to support influenza
      pandemic planning.

PMID- 29446346
TI  - Alkali-corrosion synthesis and excellent DSSC performance of novel jujube-like
      hierarchical TiO2 microspheres.
AB  - Novel jujube-like hierarchical TiO2 microspheres (HTMs) were synthesized by an
      alkali-corrosion process of titanium phosphate (Ti2O3(H2PO4)2 . 2H2O)
      microspheres. The hierarchical titanium phosphate microsphere (HTPM)
      intermediates consisting of nanoflakes with a thickness of 20 nm were firstly
      prepared by a facile hydrothermal method. After reacting with diluted NaOH at low
      temperature and atmospheric pressure, followed by subsequent acid washing and a
      calcination process, the HTPM intermediates were transformed to TiO2 with the
      microsphere morphology well retained, while the nanoflakes became porous, and
      some new nanowires were formed between the nanoflakes. Finally, HTMs consisting
      of porous nanoflakes and nanowires were obtained. The possible growth mechanisms
      of HTPMs and HTMs are discussed. The HTMs demonstrate high specific surface area
      and excellent light-scattering ability. The performance of the dye sensitized
      solar cells (DSSCs) of the HTMs synthesized under different conditions is
      studied, and a total conversion efficiency of up to 8.93% was obtained. The
      improved DSSC performance was attributed to the enhanced dye loading, light
      scattering, and charge transporting ability of the HTMs with a unique
      hierarchical nanostructure.

PMID- 29446347
TI  - Ray's Awareness. Radiation Health Effects Made Easy with Professor Dee and Doctor
      Hay.

PMID- 29446348
TI  - The effect of air stable n-doping through mild plasma on the mechanical property
      of WSe2 layers.
AB  - Two-dimensional transition metal dichalcogenides have been widely applied to
      electronic and optoelectronic device owing to their remarkable material
      properties. Many studies present the platform for regulating the contact
      resistance via various doping schemes. Here, we report the alteration of
      mechanical properties of few top layers of the WSe2 flake which are processed by
      air stable n-doping of N2O with a constant gas flow through mild plasma and
      present better manufacturability and friability. The single-line nanoscratching
      experiments on the WSe2 flakes with different doping time reveal that the
      manufacturable depths are positively correlated with the exposure time at a
      certain range and tend to be stable afterwards. Meanwhile, material
      characterization by x-ray photoelectron spectroscopy confirms that the alteration
      of mechanical properties is owing to the creation of Se vacancies and
      substitution of O atoms, which breaks the primary molecular structure of the WSe2
      flakes. The synchronous Kelvin probe force microscopy and topography results of
      ROI nanoscratching of a stepped WSe2 sample confirmed that the depth of the
      degenerate doping is five layers, which was consistent with the single-line
      scratching experiments. Our results reveal the interrelationship of the
      mechanical property, chemical bonds and work function changes of the doped WSe2
      flakes.

PMID- 29446349
TI  - Origin of noise in liquid-gated Si nanowire troponin biosensors.
AB  - Liquid-gated Si nanowire field-effect transistor (FET) biosensors are fabricated
      using a complementary metal-oxide-semiconductor-compatible top-down approach. The
      transport and noise properties of the devices reflect the high performance of the
      FET structures, which allows label-free detection of cardiac troponin I (cTnI)
      molecules. Moreover, after removing the troponin antigens the structures
      demonstrate the same characteristics as before cTnI detection, indicating the
      reusable operation of biosensors. Our results show that the additional noise is
      related to the troponin molecules and has characteristics which considerably
      differ from those usually recorded for conventional FETs without target
      molecules. We describe the origin of the noise and suggest that noise
      spectroscopy represents a powerful tool for understanding molecular dynamic
      processes in nanoscale FET-based biosensors.

PMID- 29446350
TI  - Image charge models for accurate construction of the electrostatic self-energy of
      3D layered nanostructure devices.
AB  - Efficient analytical image charge models are derived for the full spatial
      variation of the electrostatic self-energy of electrons in semiconductor
      nanostructures that arises from dielectric mismatch using semi-classical
      analysis. The methodology provides a fast, compact and physically transparent
      computation for advanced device modeling. The underlying semi-classical model for
      the self-energy has been established and validated during recent years and
      depends on a slight modification of the macroscopic static dielectric constants
      for individual homogeneous dielectric regions. The model has been validated for
      point charges as close as one interatomic spacing to a sharp interface. A brief
      introduction to image charge methodology is followed by a discussion and
      demonstration of the traditional failure of the methodology to derive the
      electrostatic potential at arbitrary distances from a source charge. However, the
      self-energy involves the local limit of the difference between the electrostatic
      Green functions for the full dielectric heterostructure and the homogeneous
      equivalent. It is shown that high convergence may be achieved for the image
      charge method for this local limit. A simple re-normalisation technique is
      introduced to reduce the number of image terms to a minimum. A number of
      progressively complex 3D models are evaluated analytically and compared with high
      precision numerical computations. Accuracies of 1% are demonstrated. Introducing
      a simple technique for modeling the transition of the self-energy between
      disparate dielectric structures we generate an analytical model that describes
      the self-energy as a function of position within the source, drain and gated
      channel of a silicon wrap round gate field effect transistor on a scale of a few
      nanometers cross-section. At such scales the self-energies become large
      (typically up to ~100 meV) close to the interfaces as well as along the channel.
      The screening of a gated structure is shown to reduce the self-energy relative to
      un-gated nanowires.

PMID- 29446351
TI  - Dynamical quantum phase transitions: a review.
AB  - Quantum theory provides an extensive framework for the description of the
      equilibrium properties of quantum matter. Yet experiments in quantum simulators
      have now opened up a route towards the generation of quantum states beyond this
      equilibrium paradigm. While these states promise to show properties not
      constrained by equilibrium principles, such as the equal a priori probability of
      the microcanonical ensemble, identifying the general properties of nonequilibrium
      quantum dynamics remains a major challenge, especially in view of the lack of
      conventional concepts such as free energies. The theory of dynamical quantum
      phase transitions attempts to identify such general principles by lifting the
      concept of phase transitions to coherent quantum real-time evolution. This review
      provides a pedagogical introduction to this field. Starting from the general
      setting of nonequilibrium dynamics in closed quantum many-body systems, we give
      the definition of dynamical quantum phase transitions as phase transitions in
      time with physical quantities becoming nonanalytic at critical times. We
      summarize the achieved theoretical advances as well as the first experimental
      observations, and furthermore provide an outlook to major open questions as well
      as future directions of research.

PMID- 29446352
TI  - Deep learning for hybrid EEG-fNIRS brain-computer interface: application to motor
      imagery classification.
AB  - OBJECTIVE: Brain-computer interface (BCI) refers to procedures that link the
      central nervous system to a device. BCI was historically performed using
      electroencephalography (EEG). In the last years, encouraging results were
      obtained by combining EEG with other neuroimaging technologies, such as
      functional near infrared spectroscopy (fNIRS). A crucial step of BCI is brain
      state classification from recorded signal features. Deep artificial neural
      networks (DNNs) recently reached unprecedented complex classification outcomes.
      These performances were achieved through increased computational power, efficient
      learning algorithms, valuable activation functions, and restricted or back-fed
      neurons connections. By expecting significant overall BCI performances, we
      investigated the capabilities of combining EEG and fNIRS recordings with state-of
      the-art deep learning procedures. APPROACH: We performed a guided left and right
      hand motor imagery task on 15 subjects with a fixed classification response time
      of 1 s and overall experiment length of 10 min. Left versus right classification
      accuracy of a DNN in the multi-modal recording modality was estimated and it was
      compared to standalone EEG and fNIRS and other classifiers. MAIN RESULTS: At a
      group level we obtained significant increase in performance when considering
      multi-modal recordings and DNN classifier with synergistic effect. SIGNIFICANCE:
      BCI performances can be significantly improved by employing multi-modal
      recordings that provide electrical and hemodynamic brain activity information, in
      combination with advanced non-linear deep learning classification procedures.

PMID- 29446353
TI  - Dermoscopy - Not just for diagnosis and not just for Dermatologists !

PMID- 29446354
TI  - Study of Adherence Pattern of Antidepressants in Patients with Depression.
AB  - Background Depression is one of the leading psychiatric disorders of the world
      affecting a person's mood, physical health and behavior. It is not permanent and
      is neither a character flaw nor a lack in discipline for a person to be ashamed
      of. It is a disorder that is reliably diagnosed and successfully treated.
      Antidepressants are the standard and the most efficacious approach to treating
      people with depression. However, adherence to treatment is necessary for
      achieving effectiveness. The result of nonadherence is severe and may cause
      therapeutic failure resulting in poor quality of life. Objective To determine the
      medication adherence pattern in patients with depression and assess the factors
      associated with non-adherence to the prescribed antidepressant therapy. Method
      Patients meeting the inclusion criteria who were diagnosed with depression were
      taken for the study. Informed consent was taken from the patients or from their
      relatives in case of their incapability. They were then interviewed using
      structured questionnaire. Result Among the 60 patients included in the study, 78%
      of them were females. Most of the patients 43% (n=26) were prescribed with
      atypical antidepressants. Less number (37%) of the patients were adherent to the
      antidepressant therapy. 68% of the females were non adherent. 82% of housewives
      were not adherent to therapy. Forgetfulness was the main reason for missing dose
      in majority (50%) of the nonadherent patients. Conclusion Majority of the
      patients with depression were non-adherent to medication. Forgetfulness was the
      major reason for missing dose in these patients.

PMID- 29446355
TI  - Incidence and Associated Risk Factors of Postoperative Sore Throat in Tertiary
      Care Hospital.
AB  - Background Postoperative sore throat is a relatively minor complaint but a
      frequent postoperative complication of anesthesia. The incidence of postoperative
      sore throat varies from 0-50% in most research studies, but some report the
      incidence is as high as 51-100% following general anesthesia. Objective The aim
      of this study was to obtain the incidence and determine the associated risk
      factors of postoperative sore throat in tertiary care hospital. Method Three
      hundred and seventy six patients who underwent various surgeries under general
      anesthesia in Dhulikhel Hospital during a four month period were included. Using
      a predesigned questionnaire with follow up after 24-30 hours after extubation,
      data was collected. Sore throat was identified using a four point scale (0-3).
      Result Overall incidence of postoperative sore throat was 50.8%. Patient with
      airway device endotracheal tubes had the highest incidence (52.2%, 176 of 337),
      and patient with i-gel had a lower incidence of sore throat (33.3%, 7 of 21).
      Female patients reported more sore throat than male, more common with older age
      group and duration of anesthesia more than two hours. Increased incidence of
      postoperative sore throat was not associated with the type of surgery, number of
      intubation attempts, category of personnel performing airway managementr and use
      of oropharyngeal airway. Conclusion Postoperative sore throat is a common
      complication of airway instrumentation in general anesthesia that can lead to
      discomfort. The overall incidence of postoperative sore throat in this study was
      50.8%. Endotracheal tube, female patients and increased duration of anesthesia
      were associated with increased postoperative sore throat rates.

PMID- 29446356
TI  - Pattern of Self-medication in Undergraduate Students at BP Koirala Institute of
      Health Sciences.
AB  - Background Self-medication is a growing health problem. It may lead to wastage of
      resources, emergence of antimicrobial resistance, adverse drug reactions and
      prolonged suffering. Little has been reported on the extent of self-medication
      practiced in medical students in Nepal. Objective To study the pattern, reason
      and perception of self-medication among undergraduate students. Method A cross
      sectional study was conducted among all undergraduate students at BP Koirala
      Institute of Health Sciences, Dharan, Nepal between April and May, 2015. After
      obtaining ethical clearance, pre-validated questionnaire was used to collect
      data. The date were analyzed and presented as frequency and percentage using SPSS
      version 11.5. Result Total of 520 students participated in the study with a mean
      age of 21.2+/-1.7 years. Prevalence of self-medication was found to be 48.3%.
      Most common cause for self-medication was common cold (53.3%). Nonsteroidal anti
      inflammatory drugs (78.9%) were the most commonly used medicine for self
      medication. The students commonly approached their seniors (50.2%) for the drug
      information. The most common adverse drug reaction experienced by the students
      was drowsiness (50.9%). Approximately one third of the students (33.2%) used to
      prescribe medicines to others. More than half of the students (53.8%) opined that
      self-medication is a part of self-care. Around one-fifth of the students (21.5%)
      students opined that self-medication is recommended by WHO. Conclusion Self
      medication is commonly practiced by undergraduate students. Nearly one third of
      the students also prescribe medicines to others. Nonsteroidal anti-inflammatory
      drugs are the most commonly used medicine as self-medication. The students need
      to be educated regarding appropriate safe-medication.

PMID- 29446357
TI  - To Access the Role of Serum Procalcitonin in Predicting the Severity of Acute
      Pancreatitis.
AB  - Background Acute Pancreatitis remains a common disorder with devastating
      consequences in severe form of disease. In this study we assessed serum
      procalcitonin for early prediction of severity of acute pancreatitis and compared
      it with multiple scoring systems and biomarkers. Objective This is a prospective
      comparative study in which 125 patients with diagnosis of acute pancreatitis were
      enrolled. All blood samples and imaging studies were obtained within 24-72 hours
      of admission and the severity was predicted. Method This is a prospective
      comparative study in which 125 patients with diagnosis of acute pancreatitis were
      enrolled. All blood samples and imaging studies were obtained within 24-72 hours
      of admission and the severity was predicted. Result Acute pancreatitis was graded
      severe in 54 patients and mild in 71 patients as per the Atlanta criteria.
      Receiver operating characteristic curve showed the area under curve of serum
      procalcitonin was higher (area under curve: 0.887, Confidence interval: 0.825
      0.948) compared to computed tomography severity index scoring system (Area under
      curve: 0.841, Confidence interval: 0.771-0.911), Ranson's score (Area under
      curve: 0.796, Confidence interval: 0.715-0.876) and C-reactive protein (Area
      under curve: 0.717, Confidence interval: 0.628-0.8.7) in predicting the severity
      of acute pancreatitis. The best cut-off value of serum procalcitonin to predict
      severe acute pancreatitis was 0.9 ng/ml with 92.6% sensitivity, 80.3%
      specificity. The accuracy of serum procalcitonin (85.6%) was better than computed
      tomography severity index score (73.6 %), Ranson's score (76.8%) and C-reactive
      protein (64.8%). Conclusion Multifactorial scoring systems are complex and hard
      to use in clinical basis. Serum procalcitonin can be used as a promising single
      biomarker, easily done in all setup with better accuracy. And it is comparable to
      computed tomography severity index and Ranson's scores in earlier prediction of
      severity of acute pancreatitis.

PMID- 29446358
TI  - Clinical Profile of Diabetic Ketoacidosis in Adults in Dhulikhel Hospital.
AB  - Background Diabetic ketoacidosis is one of the life-threatening acute
      complications of diabetes mellitus. Despite the improvements in diabetic care, it
      remains a major clinical problem in clinical practice. Objective To assess the
      clinical and laboratory profile of adults with diabetic ketoacidosis in Dhulikhel
      hospital. Method This is a descriptive cross-sectional study including adult
      patients admitted in Dhulikhel hospital from July 2014 to July 2016 with the
      diagnosis of diabetic ketoacidosis according to the guidelines of American
      diabetes association. The hospital records of these patients were reviewed for
      their clinical and biochemical profiles. Result Forty eight patients fulfilled
      the criteria of diabetic ketoacidosis and were included in the study. Seventy
      three percent of patients had type 2 diabetes mellitus. Twenty three percent of
      the patients were cases of newly diagnosed diabetes mellitus. Polyuria and
      polydipsia as presenting complaint was more common in patients with type 1
      diabetes mellitus (p=0.002) whereas fever was more common in type 2 diabetes
      mellitus patients (p=0.03). Majority of patients had normal serum sodium and
      potassium level. Forty two percent of the patients have high serum urea level and
      just over one third had high serum creatinine level. The most common
      precipitating factor of diabetic ketoacidosis for patients with type 1 diabetes
      mellitus was omission of insulin whereas in type 2 diabetic patients was
      infection. Conclusion Diabetic ketoacidosis is complication of both type 1 and
      type 2 diabetes mellitus. High degree of suspicion is needed for early detection
      of this life threatening condition especially in patients without history of
      diabetes mellitus.

PMID- 29446359
TI  - Evaluation of Risk Factors for Laryngopharyngeal Reflux among Sikkimese
      Population.
AB  - Background Laryngopharyngeal reflux is a global health problem and is associated
      with a huge economic burden and decreased quality of life. Studies describing the
      epidemiology of laryngopharyngeal reflux are sparse in India and south east Asia.
      This study becomes significant as it is being conducted in Sikkimese population
      who resides in high altitude have a different lifestyle. Objective To evaluate
      the risk factors for laryngopharyngeal reflux among Sikkimese origin. Method
      Patients of Sikkimese origin visiting Ear Nose Throat outpatient department Were
      administered with validated questionnaire. The patients were further subjected to
      validate Reflux symptom Index score. Indirect laryngoscopy was performed to
      calculate reflux finding score. Presence of laryngopharyngeal reflux was
      identified with patients having reflux symptom index and reflux finding score of
      greater or equal to 13 or more and 7 or more. Result Out of 200 subjects
      analysed, there were 77(38.5%) male and 123(61.5%) female. Heartburn and
      regurgitation were the most common symptom among the masses. Hoarseness and
      frequent throat clearance were the commonest laryngopharyngeal reflux symptoms.
      Various risk factors were computed as mentioned in the results column. Conclusion
      Study on the above mentioned population differed from rest of the country in
      terms of dietary habits. Fermented food was found to be one of the important risk
      factor for the development of laryngopharyngeal reflux in the sikkimise
      population.

PMID- 29446360
TI  - Factors Influencing Brain Drain among Nepalese Nurses.
AB  - Background Brain drain means migration of technically skilled people from one
      country to another country. Migration of health workers including nurses are the
      result of interplay of many push and pull factors. Push factors are those
      conditions that influence the nurses' decision to leave their own country.
      Conversely, pull factors are those conditions in a given country that attract
      nurses, influencing their movement to that country. Objective The objective of
      this study was to identify push and pull factors of brain drain among the
      Nepalese nurses. Method Descriptive cross sectional study was done among 228
      Nepalese nurses working in five different countries in 2016 by using quota
      sampling technique. A self administered questionnaire consisting of structured
      four-point Likert scale was designed to collect information on push and pull
      factors of brain drain. Descriptive and inferential statistics were computed
      using SPSS version 16. Result Many of brain drained nurses had ranked very
      important push factor was personal ambition (72.8%) and very important pull
      factor was better job and career opportunity (77.2%). Majority of nurses working
      in Nepal had ranked very important push factor was lack of job and career
      opportunity (86.0%) and pull factor was better job and career opportunity
      (85.1%). All push and pull factors were significantly associated with brain
      drain. Conclusion Most of the Nepalese nurses were forced to go abroad due to
      personal ambition, followed by low salary, and lack of job and career
      opportunity. Nurse migration out of Nepal is likely to persist and even increase
      if underlying factors aren't properly resolved.

PMID- 29446361
TI  - Outcome of Patients with Meningitis and Encephalitis at Tertiary Care Hospital in
      Eastern Nepal.
AB  - Background There are several etiologies of meningitis and encephalitis which must
      be considered in any patient presenting with fever, headache, neck stiffness and
      vomiting. Bacterial meningitis and viral encephalitis are medical emergencies and
      need urgent attention and treatment. Any delay in diagnosis and treatment has
      been shown to increase morbidity and mortality. Some of the survivors also have
      neurological sequel with a need for long term physical and occupational
      rehabilitation. Objective To find out common causes of meningitis, encephalitis,
      predictors of outcome, early and late complications of meningitis and
      encephalitis at Tertiary Care Hospital in Eastern Nepal. Method It is a
      prospective study which was conducted at Nobel Medical College Teaching Hospital
      from April 2015 to March 2016. Result A total of 52 patients participated in the
      study. Bacterial meningitis was the most common type of neuroinfection (40.4%)
      followed by tubercular meningitis (27%), viral encephalitis (17.3%) and viral
      meningitis (15.4%). Pneumococcus was the most common identified cause of
      meningitis accounting for 28.9% of bacterial meningitis. Japanese encephalitis
      was the most common identifiable cause of encephalitis accounting for 33% of
      cases. Low Glasgow Coma Scale at admission was significantly associated with
      worse neurological outcome (P<0.001). Similarly, high white blood cell count in
      blood was associated with worse neurological outcome (P=0.001). Conclusion
      Meningitis and encephalitis are neurological emergency. Prompt diagnosis and
      treatment is needed to improve survival. Neurological sequel is common after
      those infections which require long term rehabilitation.

PMID- 29446362
TI  - A Survey on Oral Health and Practice of Nepalese in Areas Affected by Earthquake
      in 2015.
AB  - Background Understanding post-earthquake oral health indicators is essential for
      developing oral health interventions of the victims. Presumably, due to a
      geographic difficulty, there has been no investigation to reveal the oral health
      status of individuals after the Gorkha earthquake in Nepal. Objective The main
      objective was to determine the oral health and practice of Nepalese affected by
      earthquake in April-May, 2015. Method The epidemiological cross sectional study
      was done at 5 different districts (Sindhupalchok, Dadhing, Bhaktapur, Kathmandu
      and Kavre) of Nepal from September till November, 2015. Altogether 500 subjects
      aged form 16 to 80 years of age living in the transitional shelters community
      were included in earthquake-affected areas. Different parameters were studied
      from past and present medical and dental problems, habits, oral hygiene habits.
      DMFT, gingival index, periodontal index were studied and correlation was studied
      among them. Result It shows that 98% of the participants had plaque and 96.4% of
      the participants had calculus. Mean decayed was 9, mean missing was 4 and mean
      filling was 1. 22.60% of the participants had score 0, 34.8% had score 1, 34% had
      score 2 and 8.60% had score 3 of mean gingivitis index. 10% of the participants
      showed score 0, 36% showed score 1, 35% showed score 2, 10.2% showed score 3 and
      8.2% showed score 4 of mean periodontal index. Moreover, significant correlation
      was observed among DMFT index, gingival index and periodontal index (p<0.001).
      Conclusion The oral health care practice, oral hygiene habits, nutritional intake
      of the people have been affected in the earthquake affected areas. It showed high
      caries index, gingival index and periodontal index in earthquake affected people
      suggesting further efforts are needed for an oral health improvement. Data from
      this study may be used as basic information for oral health planning and future
      steps in oral health care preventive and therapeutic programs.

PMID- 29446363
TI  - Histopathological Analysis of Non-Neoplastic Superficial Lymphadenopathies.
AB  - Background Lymphadenopathies are the clinical manifestation of enlargement of
      lymph nodes which are a common occurrence and are processes of lymph nodes in
      response to a variety of exogenous and endogenous stimulants. The vast majority
      of enlarged lymph nodes are non- neoplastic. Objective The objective of the study
      is to analyze the spectrum of non-neoplastic lesions of superficial
      lymphadenopathies with their histomorphological features. Method This was a
      retrospective hospital based study done in the department of Pathology. All cases
      of superficial lymph node biopsies received during a period of 7 years were
      retrieved and divided into 2 broad categories: neoplastic and non-neoplastic. The
      latter group is the material for the present study. The diagnosis was made on
      morphological basis. Result Of all the 268 superficial lymph node biopsies, 25.4%
      (68 cases) were neoplastic and 74.6% (200 cases) were non-neoplastic. The non
      neoplastic cases were further categorized into non-infectious 60.5% (121 cases)
      and infectious 39.5% (79 cases). Neck node (70%) was the most common site of
      involvement. There were 102 male and 98 female patients with male to female ratio
      1.04:1. The age range of the patients was 2 years to 83 years with a mean of
      27.16 years and most common being 11-20 years 29% (58 cases). Majority of the
      cases were non-specific reactive lymphadenitis 84.3% (102 cases) followed by
      tuberculosis 36.5% (73 cases). Conclusion The major cause for the superficial
      lymphadenopathy was found to be non-neoplastic etiology with slight male
      predominance. Reactive lymphadenitis was the leading cause unlike the studies
      done in other Asian and Tropical countries where tuberculosis was more common.

PMID- 29446364
TI  - Characterization of Seasonal Influenza Virus Type and Subtypes Isolated from
      Influenza Like Illness Cases of 2012.
AB  - Background Seasonal influenza is one of the increasing public health burdens in
      Nepal. Objective The objective of this study was to isolate and characterize the
      influenza virus type and subtypes of Nepal. Method A total of 1536 throat swab
      specimens were collected from January to December 2012. Total ribonucleic acid
      was extracted using Qiagen viral nucleic acid extraction kit and polymerase chain
      reaction assay was performed following the US; CDC Real-time PCR protocol. Ten
      percent of positive specimens were inoculated onto Madin-Darby Canine Kidney
      cells. Isolates were characterized by using reference ferret antisera. Result Of
      the total specimens (n=1536), influenza virus type A was detected in 196 (22%)
      cases; of which 194 (99%) were influenza A (H1N1) pdm09 and 2 (1 %) were
      influenza A/H3 subtype. Influenza B was detected in 684 (76.9%) cases. Influenza
      A (H1N1) pdm09, A/H3 and influenza B virus were antigenically similar to the
      recommended influenza virus vaccine candidate of the year 2012. Although sporadic
      cases of influenza were observed throughout the year, peak was observed during
      July to November. Conclusion Similar to other tropical countries, A (H1N1) pdm09,
      A/H3 and influenza B viruses were co-circulated in Nepal.

PMID- 29446365
TI  - Determination of Sex from the Foramen Magnum using 3DCT: A Nepalese Study.
AB  - Background Identification is of utmost importance in any medicolegal
      investigation with sex determination being one of the principle indicators of
      identity. Sexing of bones becomes easy when the skeletal remains are complete.
      However, the problem arises when the bones are fragmented. Many researchers have
      undertaken several studies in different populations to determine the sex with
      reasonable accuracy using numerous measurements of the skull including those of
      the foramen magnum. Objective The present study was aimed to find the sexual
      dimorphism of the foramen magnum in the Nepalese population by analyzing the
      antero-posterior length, transverse diameter and area of the foramen magnum.
      Method The antero-posterior length and transverse diameter of the foramen magnum
      were measured using three-dimensional computed tomography (3DCT) images of the
      head in a cohort of 100 Nepalese subjects. Radinsky's and Teixeria's formulae
      were used to calculate the area of the foramen magnum. Discriminate function
      analysis was used to analyze sex differences. Result Mean values of antero
      posterior length and transverse diameter of the foramen magnum in males were
      higher than in females. The mean of the area calculated using Radinsky's formula
      was smaller than that calculated by Teixeira's formula and the areas calculated
      were higher in males. The measurements of the foramen magnum and the areas
      calculated showed significant difference (p<0.001) between males and females.
      Discriminate function analysis for the measurements of the foramen magnum and the
      areas calculated showed high predictability for both the sexes. Discriminate
      function analysis showed a maximum predictability of 75%. Conclusion Considering
      the percent of predictability of sex from the various variables related to the
      foramen magnum in the Nepalese population, it can be concluded that its
      restricted applicability in forensic investigations should be constrained to
      cases of fragmentary skull bases.

PMID- 29446366
TI  - Incidence and Pattern of Impaction of Mandibular Third Molars : A Single
      Institutional Experience in Nepal.
AB  - Background Impacted teeth are those that have erupted or are partially erupted
      and will not assume a normal arch relationship with opposing and adjacent teeth
      and tissues. Objective To evaluate the incidence and pattern of mandibular
      impacted third molars in patients of Dhulikhel Hospital. Method A retrospective
      study was conducted from March 2016 to November 2016 and reviewed 581
      orthopantomograms and clinical records of patients who presented to the
      Department of Oral and Maxillofacial Surgery. The angulation of impaction was
      measured using Winter's classification and the level and position of impacted
      third molar was recorded using Pell and Gregory classification system. The
      etiology for extraction was recorded from previous clinical records. Result In
      this study, incidence of impaction was more prevalent in females. The most common
      pattern of impaction was mesioangular followed by horizontal, vertical,
      distoangular and others. The most common cause of extraction was caries in the
      third molar. There was no significant difference between the pattern of impaction
      in the right and left sides of the mandible. Conclusion Classifications of
      impacted mandibular third molars can be effectively used to predict the surgical
      difficulty and to evaluate the risk of postoperative complications. Therefore,
      this study highlights the importance of evaluation of pattern, type and class of
      impaction in Nepalese population giving a high clinical significance.

PMID- 29446367
TI  - Computed Tomographic Evaluation of Craniocerebral Trauma in Dhulikhel Hospital.
AB  - Background Craniocerebral trauma is common health problem in emergency department
      of any hospital. CT is commonly indicated to to rule out any significant
      intracranial abnormalities in these patients, so that timely intervention of the
      significant intracranial pathologies can be done. Objective The study is done to
      evaluate CT findings of head injury patients in Dhulikhel Hospital. Method This
      prospective hospital based study was done in Department of Radiology of Dhulikhel
      Hospital in the period of January 2015 to December 2015. CT findings of the head
      trauma patients undergoing CT in the Department of Radiology were reviewed and
      analysed. Result The study was done in 484 patients, 165 female and 319 male
      patients. Mean age of the patients was 30.87 +/- 19.25 years. Among them 205
      patients showed abnormal CT findings, scalp injury being the commonest one,
      followed by skull fracture. 60 patients showed abnormal intracranial findings.
      There was significant correlation of skull fracture and abnormal intracranial
      findings in this study. Conclusion This study provided the normal and abnormal CT
      findings in head of the craniocerebral trauma patients in Dhulikhel Hospital.
      Abnormal CT findings were predominantly extra-cranial and were overlapping with
      intracranial abnormal findings.

PMID- 29446368
TI  - Awareness and Knowledge of Oral Cancer among Medical Students in Kathmandu
      University School of Medical Sciences.
AB  - Background Oral cancer is a major public health problem worldwide. It has high
      mortality rates and chances of survival is relatively superior when detected
      early. Lack of knowledge and awareness about oral cancer among medical students
      may contribute to delay in diagnosis and treatment. Objective To assess awareness
      and knowledge of oral cancer among medical students. Method A cross-sectional
      study conducted among 286 students by Department of Otorhinolaryngology and Head
      & Neck surgery, Kathmandu University School of Medical sciences between July to
      August 2016. A questionnaire with questions on socio-demographic profile,
      awareness and knowledge of oral cancer was used. Independent sample t test and
      Pearson Chi-square tests were used for statistical analysis. Result Out of 329
      students approached, 286 participated in the study yielding a response rate of
      86.9%. Symptoms of oral cancer as reported were ulceration in mouth (92.3%), oral
      bleeding (85.0%),whitish or reddish patch (84.3%), halitosis (75.5%) and swelling
      in neck (74.5%), trismus (69.2%), numbness (67.1%), loosening of teeth (49.3%)
      and tooth sensitivity (41.6%). The perceived risk factors were smoking (97.2%),
      tobacco chewing (96.5%), chronic irritation (86.7%), immunodeficiency (83.9%),
      poor oral hygiene (88.5%), human papilloma virus infection (82.5%), dietary
      factors (81.1%), alcohol (79.4%), ill-fitting dentures (72.4%), hot spicy food
      (65.4%) and hot beverages (58.0%). Significant differences were found between pre
      clinical and clinical students for knowledge of risk factors, signs and symptoms
      of oral cancer (p<0.001). Conclusion There is deficiency of knowledge among
      medical students about some aspects of oral cancer. Active involvement while
      examining patients and taking biopsies of malignant and premalignant lesions may
      help in improving students' knowledge about oral cancer.

PMID- 29446369
TI  - Diabetic Retinopathy Awareness among Diabetic Patients Attending COMS-TH.
AB  - Background Diabetic retinopathy (DR) is one of the leading causes of blindness in
      Nepal. Objective The main objective of the study is to know the awareness of
      diabetic retinopathy among new cases of diabetes mellitus (DM) attending the
      college of medical science- teaching hospital, Bharatpur, Nepal. Method All the
      diabetic cases referred for ophthalmic consultation and also referred outpatient
      department cases from other departments to ophthalmic outpatient department was
      carried out. Detailed demographics of the subjects and their awareness of
      potential ocular problems from diabetes mellitus were noted. Result Total one
      hundred and thirty-one patients were enrolled during the study period from 15
      November 2016 to 15 May 2017. Brahmin 39.69% and 19.08% Mongolian were the most
      predominant ethnical group. The predominant group of patients were housewives
      (41.22%) then followed by service (19.85%), business (13.74%), agriculture
      (12.21%), others (12.98%). Among 36.64% of the literate patients, 19.85% had
      passed school level, 9.92% had passed intermediate level, 88.55% were aware of
      Diabetic retinopathy. Among them majority 88.55% were referred by physician.
      Family history were present in 35.68% and fundus evaluation was done for the
      first time in almost half of diabetic cases (64.12%) and diabetic retinopathy was
      found in 32.06% of total cases in right eye and 30.53% of total cases in left
      eye. Conclusion Along with the awareness, routine dilated fundoscopy is mandatory
      for slight threating stage of retinopathy and to reduce the burden of blindness
      from diabetic retinopathy in Nepal.

PMID- 29446370
TI  - Correlation between Preoperative High Resolution Computed Tomography (CT)
      Findings with Surgical Findings in Chronic Otitis Media (COM) Squamosal Type.
AB  - Background The exact role of High resolution computed tomography (HRCT) temporal
      bone in preoperative assessment of Chronic suppurative otitis media atticoantral
      disease still remains controversial. Objective To evaluate the role of high
      resolution computed tomography temporal bone in Chronic suppurative otitis media
      atticoantral disease and to compare preoperative computed tomographic findings
      with intra-operative findings. Method Prospective, analytical study conducted
      among 65 patients with chronic suppurative otitis media atticoantral disease in
      Department of Radiodiagnosis, Kathmandu University Dhulikhel Hospital between
      January 2015 to July 2016. The operative findings were compared with results of
      imaging. The parameters of comparison were erosion of ossicles, scutum, facial
      canal, lateral semicircular canal, sigmoid and tegmen plate along with extension
      of disease to sinus tympani and facial recess. Sensitivity, specificity, negative
      predictive value, positive predictive values were calculated. Result High
      resolution computed tomography temporal bone offered sensitivity (Se) and
      specificity (Sp) of 100% for visualization of sigmoid and tegmen plate erosion.
      The performance of HRCT in detecting malleus (Se=100%, Sp=95.23%), incus
      (Se=100%,Sp=80.48%) and stapes (Se=96.55%, Sp=71.42%) erosion was excellent. It
      offered precise information about facial canal erosion (Se=100%, Sp=75%), scutum
      erosion (Se=100%, Sp=96.87%) and extension of disease to facial recess and sinus
      tympani (Se=83.33%,Sp=100%). high resolution computed tomography showed
      specificity of 100% for lateral semicircular canal erosion (Sp=100%) but with low
      sensitivity (Se=53.84%). Conclusion The findings of high resolution computed
      tomography and intra-operative findings were well comparable except for lateral
      semicircular canal erosion. high resolution computed tomography temporal bone
      acts as a road map for surgeon to identify the extent of disease, plan for
      appropriate procedure that is required and prepare for potential complications
      that can be encountered during surgery.

PMID- 29446371
TI  - Regarding "Haemolytic Effects of Hypo-osmotic Salt Solutions on Human
      Erythrocytes" in Kathmandu University Medical Journal 2011;34(2):35-9.

PMID- 29446372
TI  - Regarding "Ultrasound Guided Femoral Nerve Block to Provide Analgesia for
      Positioning Patients with Femur Fracture Before Subarachnoid Block: Comparison
      with Intravenous Fentanyl" in Kathmandu University Medical Journal 2016;54(2):125
      9.

PMID- 29446373
TI  - Gene-environment Interaction: The Causes of High Obesity Incidence.
AB  - Urbanization has provided experimental settings for testing the interactive
      relationship between genetic background and changes in lifestyle and dietary
      patterns. The concept of gene-environment interaction was described by epidemic
      of obesity along with urbanization. Genome-wide association has identified
      several genes such as melanocortin-4 receptor that associates with environmental
      influences of obesity. Gene environment (GxE) interaction refers to modification
      by an environmental factor of the effect of a genetic variant on a phenotypic
      trait. GxE interactions can serve to modulate the adverse effects of a risk
      allele, or can exacerbate the genotype-phenotype relationship and increase risk.

PMID- 29446374
TI  - Subtotal Petrosectomy and Cochlear Implant Placement in Otologic Presentation of
      "Wegener's Granulomatosis".
AB  - Granulomatosis with polyangitis is a rare granuloma forming necrotizing
      vasculitis, which involves mainly the respiratory tract and renal system.
      Otologic involvement may occur primarily as chronic serous otitis media and
      chronic silent mastoiditis with conductive hearing loss and may rarely lead to
      sensorineural hearing loss requiring cochlear implantation. This case describes a
      patient with granulomatous poylangitis with profound sensorineural hearing loss
      who underwent subtotal petrosectomy with cochlear implantation.

PMID- 29446375
TI  - Upper Gastrointestinal Bleeding in Aluminium Phosphide Poisoning.
AB  - Aluminium phosphide is one of the most common poisons used for suicide in an
      agricultural country like India. Death is usually due to myocarditis which occurs
      within few hours of ingestion. There are many late complications reported in
      medical literature, however toxic effects on the gastrointestinal system,
      particularly corrosive action leading to massive haemorrhage is rarely reported.
      A 30 year old male developed upper gastrointestinal bleeding on the second day
      after consumption of aluminium phosphide. An exploratory laprotomy was done
      followed by adhesinolysis, gastrostomy closure with feeding jejunostomy and
      drainage. He died after eight days of ingestion. The autopsy findings of this
      rarely reported case along with review of literature on corrosive action of
      Aluminium Phosphide is discussed.

PMID- 29446376
TI  - Platelet Rich Fibrin in Management of Complex Endoperio Cases.
AB  - Endo-perio lesions have been a dilemma to the dental practitioner. Both tissues
      share the same anatomical origin. Sometimes exact etiological passage of disease
      process cannot be traced; nevertheless traditional and newer treatment modalities
      must be employed to ensure best treatment possibilities. Patient reported with
      pain and pus exudates in upper left anterior region. Past dental history revealed
      no history of trauma. Initial examination revealed draining sinus with respect to
      22. However, no Caries and pockets could be detected. Tooth was nonresponsive to
      vitality test. Patient symptoms did not relieve even two months after completion
      of RCT. Apical surgery was planned. Apicectomy was done and osseous defect was
      filled with PRF coagulum. Patient was followed up every three months and showed
      complete resolution of all symptoms. Radiographs showed complete resolution of
      osseous defect in nine months. PRF can be used to enhance bone augmentation in
      treatment of periapical defects as a potential treatment alternative for faster
      healing.

PMID- 29446377
TI  - Therapeutic Effects of a Long-Acting Cholinergic Receptor Blocker, Tiotropium
      Bromide, on Asthma.
AB  - BACKGROUND The aim of this study was to evaluate the therapeutic effects of
      tiotropium bromide on asthma. MATERIAL AND METHODS A total of 160 patients with
      moderate persistent asthma were randomly divided into 4 groups (n=40): the 3
      control groups were given fluticasone propionate aerosol (group A), salmeterol
      fluticasone propionate inhalant (group B), and tiotropium bromide inhalation
      powder combined with salmeterol-fluticasone propionate inhalant (group C),
      respectively, and the experimental group received tiotropium bromide inhalation
      powder combined with fluticasone propionate aerosol (group D) and salbutamol was
      used to relieve symptoms when necessary. RESULTS After 8 weeks of treatment, the
      pulmonary function of group D, which was significantly better than those of group
      A (P<0.05), was similar to those of groups B and C (P>0.05). Group D had
      significantly better asthma control test scores and nighttime symptom scores than
      in group A (P<0.05), without significant differences from those of group B or
      group C (P>0.05). The number of times salbutamol was used to alleviate symptoms
      was significantly different (P<0.05) between group D and group A (P<0.05), as
      well as between group C and group D (P<0.05). Groups D and B had similar results
      (P>0.05). IL-13 levels in induced sputum had significant differences (P<0.05).
      The levels in group D, which were higher than those of groups A and B (P<0.05),
      were similar to those of group C (P>0.05). CONCLUSIONS Tiotropium bromide
      combined with fluticasone propionate improved the respiratory function and
      quality of life, and is a new therapy for moderate, persistent asthma.

PMID- 29446378
TI  - Freezing on a sphere.
AB  - The best understood crystal ordering transition is that of two-dimensional
      freezing, which proceeds by the rapid eradication of lattice defects as the
      temperature is lowered below a critical threshold. But crystals that assemble on
      closed surfaces are required by topology to have a minimum number of lattice
      defects, called disclinations, that act as conserved topological charges-consider
      the 12 pentagons on a football or the 12 pentamers on a viral capsid. Moreover,
      crystals assembled on curved surfaces can spontaneously develop additional
      lattice defects to alleviate the stress imposed by the curvature. It is therefore
      unclear how crystallization can proceed on a sphere, the simplest curved surface
      on which it is impossible to eliminate such defects. Here we show that freezing
      on the surface of a sphere proceeds by the formation of a single, encompassing
      crystalline 'continent', which forces defects into 12 isolated 'seas' with the
      same icosahedral symmetry as footballs and viruses. We use this broken symmetry
      aligning the vertices of an icosahedron with the defect seas and unfolding the
      faces onto a plane-to construct a new order parameter that reveals the underlying
      long-range orientational order of the lattice. The effects of geometry on
      crystallization could be taken into account in the design of nanometre- and
      micrometre-scale structures in which mobile defects are sequestered into self
      ordered arrays. Our results may also be relevant in understanding the properties
      and occurrence of natural icosahedral structures such as viruses.

PMID- 29446379
TI  - Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression.
AB  - Enhanced bursting activity of neurons in the lateral habenula (LHb) is essential
      in driving depression-like behaviours, but the cause of this increase has been
      unknown. Here, using a high-throughput quantitative proteomic screen, we show
      that an astroglial potassium channel (Kir4.1) is upregulated in the LHb in rat
      models of depression. Kir4.1 in the LHb shows a distinct pattern of expression on
      astrocytic membrane processes that wrap tightly around the neuronal soma.
      Electrophysiology and modelling data show that the level of Kir4.1 on astrocytes
      tightly regulates the degree of membrane hyperpolarization and the amount of
      bursting activity of LHb neurons. Astrocyte-specific gain and loss of Kir4.1 in
      the LHb bidirectionally regulates neuronal bursting and depression-like symptoms.
      Together, these results show that a glia-neuron interaction at the perisomatic
      space of LHb is involved in setting the neuronal firing mode in models of a major
      psychiatric disease. Kir4.1 in the LHb might have potential as a target for
      treating clinical depression.

PMID- 29446380
TI  - Pulsating aurora from electron scattering by chorus waves.
AB  - Auroral substorms, dynamic phenomena that occur in the upper atmosphere at night,
      are caused by global reconfiguration of the magnetosphere, which releases stored
      solar wind energy. These storms are characterized by auroral brightening from
      dusk to midnight, followed by violent motions of distinct auroral arcs that
      suddenly break up, and the subsequent emergence of diffuse, pulsating auroral
      patches at dawn. Pulsating aurorae, which are quasiperiodic, blinking patches of
      light tens to hundreds of kilometres across, appear at altitudes of about 100
      kilometres in the high-latitude regions of both hemispheres, and multiple patches
      often cover the entire sky. This auroral pulsation, with periods of several to
      tens of seconds, is generated by the intermittent precipitation of energetic
      electrons (several to tens of kiloelectronvolts) arriving from the magnetosphere
      and colliding with the atoms and molecules of the upper atmosphere. A possible
      cause of this precipitation is the interaction between magnetospheric electrons
      and electromagnetic waves called whistler-mode chorus waves. However, no direct
      observational evidence of this interaction has been obtained so far. Here we
      report that energetic electrons are scattered by chorus waves, resulting in their
      precipitation. Our observations were made in March 2017 with a magnetospheric
      spacecraft equipped with a high-angular-resolution electron sensor and
      electromagnetic field instruments. The measured quasiperiodic precipitating
      electron flux was sufficiently intense to generate a pulsating aurora, which was
      indeed simultaneously observed by a ground auroral imager.

PMID- 29446383
TI  - Coordinate international Earth observations for maximum impact.

PMID- 29446381
TI  - Ketamine blocks bursting in the lateral habenula to rapidly relieve depression.
AB  - The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted
      enormous interest in mental health research owing to its rapid antidepressant
      actions, but its mechanism of action has remained elusive. Here we show that
      blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the
      lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in
      rat and mouse models of depression. LHb neurons show a significant increase in
      burst activity and theta-band synchronization in depressive-like animals, which
      is reversed by ketamine. Burst-evoking photostimulation of LHb drives behavioural
      despair and anhedonia. Pharmacology and modelling experiments reveal that LHb
      bursting requires both NMDARs and low-voltage-sensitive T-type calcium channels
      (T-VSCCs). Furthermore, local blockade of NMDAR or T-VSCCs in the LHb is
      sufficient to induce rapid antidepressant effects. Our results suggest a simple
      model whereby ketamine quickly elevates mood by blocking NMDAR-dependent bursting
      activity of LHb neurons to disinhibit downstream monoaminergic reward centres,
      and provide a framework for developing new rapid-acting antidepressants.

PMID- 29446382
TI  - A spin-orbital-entangled quantum liquid on a honeycomb lattice.
AB  - The honeycomb lattice is one of the simplest lattice structures. Electrons and
      spins on this simple lattice, however, often form exotic phases with non-trivial
      excitations. Massless Dirac fermions can emerge out of itinerant electrons, as
      demonstrated experimentally in graphene, and a topological quantum spin liquid
      with exotic quasiparticles can be realized in spin-1/2 magnets, as proposed
      theoretically in the Kitaev model. The quantum spin liquid is a long-sought
      exotic state of matter, in which interacting spins remain quantum-disordered
      without spontaneous symmetry breaking. The Kitaev model describes one example of
      a quantum spin liquid, and can be solved exactly by introducing two types of
      Majorana fermion. Realizing a Kitaev model in the laboratory, however, remains a
      challenge in materials science. Mott insulators with a honeycomb lattice of spin
      orbital-entangled pseudospin-1/2 moments have been proposed, including the 5d
      electron systems alpha-Na2IrO3 (ref. 5) and alpha-Li2IrO3 (ref. 6) and the 4d
      electron system alpha-RuCl3 (ref. 7). However, these candidates were found to
      magnetically order rather than form a liquid at sufficiently low temperatures,
      owing to non-Kitaev interactions. Here we report a quantum-liquid state of
      pseudospin-1/2 moments in the 5d-electron honeycomb compound H3LiIr2O6. This
      iridate does not display magnetic ordering down to 0.05 kelvin, despite an
      interaction energy of about 100 kelvin. We observe signatures of low-energy
      fermionic excitations that originate from a small number of spin defects in the
      nuclear-magnetic-resonance relaxation and the specific heat. We therefore
      conclude that H3LiIr2O6 is a quantum spin liquid. This result opens the door to
      finding exotic quasiparticles in a strongly spin-orbit-coupled 5d-electron
      transition-metal oxide.

PMID- 29446384
TI  - Find drugs that delay many diseases of old age.

PMID- 29446385
TI  - Brainpower boost for birds in large groups.

PMID- 29446386
TI  - Don't jump to conclusions about climate change and civil conflict.

PMID- 29446389
TI  - Deluge of astronomical data will soon hit South Africa.

PMID- 29446390
TI  - US science agency will require universities to report sexual harassment.

PMID- 29446387
TI  - On the trail of invasive cells in breast cancer.

PMID- 29446388
TI  - Train PhD students to be thinkers not just specialists.

PMID- 29446392
TI  - Trump science budget sows confusion.

PMID- 29446394
TI  - The quantum internet has arrived (and it hasn't).

PMID- 29446391
TI  - Watch your language.

PMID- 29446395
TI  - A guide to juggling fieldwork and pregnancy.

PMID- 29446396
TI  - Tree rings reveal increased fire risk for southwestern US.

PMID- 29446397
TI  - Corrections.

PMID- 29446398
TI  - The two faces of a magnetic honeycomb.

PMID- 29446399
TI  - US bill illustrates how conservation triage can lead to extinctions.

PMID- 29446400
TI  - Japanese photo of Rosalind Franklin unearthed.

PMID- 29446401
TI  - Working memory freed from the past.

PMID- 29446405
TI  - Spaceflight success, harassment policy and ancestry research.

PMID- 29446404
TI  - Wild primates threaten efforts to wipe out skin disease.

PMID- 29446407
TI  - SpaceX ignites big dreams.

PMID- 29446408
TI  - Burst firing sets the stage for depression.

PMID- 29446409
TI  - Better management of groundwater needed in Pakistan.

PMID- 29446410
TI  - Teach young scientists the importance of societal impact for research.

PMID- 29446412
TI  - From proposals to snarks: the messages that scientists sneak into their papers.

PMID- 29446411
TI  - The origin of pulsating auroras.

PMID- 29446413
TI  - Corrigendum to "Biomarker MicroRNAs for Diagnosis of Oral Squamous Cell Carcinoma
      Identified Based on Gene Expression Data and MicroRNA-mRNA Network Analysis".
AB  - [This corrects the article DOI: 10.1155/2017/9803018.].

PMID- 29446414
TI  - Air promoted annulation of thiophenols with alkynes leading to benzothiophenes.
AB  - Air promoted intermolecular annulation of thiophenols with alkynes, leading to
      complex benzothiophenes, is reported. This atom-economical reaction is performed
      in the absence of any catalyst, chemical oxidant and additive. Only a solvent and
      an air atmosphere were required. A plausible radical involved mechanism is
      proposed.

PMID- 29446416
TI  - Copper-catalyzed aerobic cyclizations of tetrahydroisoquinolines with
      bromoketones and alkenes for the synthesis of 5,6-dihydropyrrolo[2,1
      a]isoquinolines.
AB  - A new copper-catalyzed oxidative cyclization protocol was developed for the
      synthesis of 5,6-dihydropyrrolo[2,1-a]isoquinolines via a three-component
      reaction of tetrahydroisoquinolines with bromoketones and electron-deficient
      alkenes with air as a terminal oxidant. A variety of functional groups survived
      under the reaction conditions and the target products were obtained in good
      yields. This reaction features such advantages as eco-friendly reaction
      conditions, a simplified operation process and a broad substrate scope.

PMID- 29446415
TI  - Highly sensitive and selective multidimensional resistive strain sensors based on
      a stiffness-variant stretchable substrate.
AB  - Highly stretchable strain sensors that are capable of collecting complex multi
      axial, multidimensional strain information in real time are crucial in practical
      applications for human motion detection. Here we present a highly sensitive and
      selective multidimensional resistive strain sensor based on a monolithic
      integration of a stiffness-variant stretchable substrate and sensing film
      comprising a cross-shaped silver nanowire percolation network in a single device.
      The multidimensional strain sensor efficiently distinguishes strains in various
      directions with a large gauge factor (GF) of >20 and a wide strain-detectable
      range of up to 60%. The sensor also features a maximum difference in GF between
      the x- and y-axes of >20 and long-term performance stability for up to 500 strain
      cycles. The practicality of the sensor as a human motion detector is demonstrated
      by attaching it directly to a part of the human body and measuring the
      multidimensional strains that occur during motions in real time.

PMID- 29446417
TI  - An efficient synthesis of 16H-dibenzo[2,3:6,7][1,4]oxazepino[5,4-b]quinazolin-16
      ones via an Ullmann reaction catalyzed by CuI.
AB  - CuI functions as a mild Lewis acid catalyst to promote the condensation and
      cyclization reaction of 2-amino-N-(2-hydroxyphenyl)benzamide and 2
      bromobenzaldehyde to build the quinazoline moiety first. With the addition of
      Cs2CO3, it also can catalyse the subsequent intramolecular Ullmann type reaction
      to give 16H-dibenzo[2,3:6,7][1,4]oxazepino[5,4-b]quinazolin-16-ones in good
      yields.

PMID- 29446418
TI  - Carbon nanotube aerogel-CoS2 hybrid catalytic counter electrodes for enhanced
      photovoltaic performance dye-sensitized solar cells.
AB  - The carbon nanotube aerogel (CNA) with an ultra-low density, three-dimensional
      network nanostructure, superior electronic conductivity and large surface area is
      being widely employed as a catalytic electrode and catalytic support.
      Impressively, dye-sensitized solar cells (DSSCs) assembled with a CNA counter
      electrode (CE) achieved a maximum power conversion efficiency (PCE) of 8.28%,
      which exceeded that of the conventional platinum (Pt)-based DSSC (7.20%) under
      the same conditions. Furthermore, highly dispersed CoS2 nanoparticles endowed
      with excellent intrinsic catalytic activity were hydrothermally incorporated to
      form a CNA-supported CoS2 (CNA-CoS2) CE, which was due to the large number of
      catalytically active sites and sufficient connections between CoS2 and the CNA.
      The electrocatalytic ability and stability were systematically evaluated by
      cyclic voltammetry (CV), electrochemical impedance spectra (EIS) and Tafel
      polarization, which confirmed that the resultant CNA-CoS2 hybrid CE exhibited a
      remarkably higher electrocatalytic activity toward I3- reduction, and faster ion
      diffusion and electron transfer than the pure CNA CE. Such cost-effective DSSCs
      assembled with an optimized CNA-CoS2 CE yielded an enhanced PCE of 8.92%,
      comparable to that of the cell fabricated with the CNA-Pt hybrid CE reported in
      our published literature (9.04%). These results indicate that the CNA-CoS2 CE can
      be considered as a promising candidate for Pt-free CEs used in low-cost and high
      performance DSSCs.

PMID- 29446419
TI  - A semi-permanent and durable nanoscale-crack-based sensor by on-demand healing.
AB  - Although sensitivity and durability are desirable in a sensor, both of them
      cannot be easily achieved. Site-specific and effective signal acquisition on the
      limited area of a sensor inevitably allows fatigue accumulation and
      contamination. For example, an ultrasensitive nanoscale-crack-based sensor for
      detecting a mechanical stimulus with tremendous sensitivity (a gauge factor
      greater than 2000 under 2% strain), yet limited durability (up to a few thousand
      stretching cycles in tensile tests) has been presented previously. Herein, we
      suggest a simple yet robust nanoscale-crack-based sensor that achieves remarkable
      durability through the use of a self-healable polymer. The self-healable polymer
      helps the crack gap recover and maintain high stability for 1 million cycles
      under 2% strain. Moreover, site-specific recovery with infrared light irradiation
      was demonstrated with monolithic arrayed sensors. The proposed strategy provides
      a unique solution to achieving highly enhanced durability and high
      mechanosensitivity, which are typically incompatible.

PMID- 29446420
TI  - Newly synthesized quercetin derivatives as corrosion inhibitors for mild steel in
      1 M HCl: combined experimental and theoretical investigation.
AB  - To evaluate the corrosion inhibition efficacy of the derivatives of naturally
      available organics, mono and di-4-((2-hydroxyethyl)piperazin-1-yl)methyl
      derivatives of quercetin, a flavonoid, have been synthesized. Their potential as
      anti-corrosive agents is assessed for mild steel in 1 M HCl employing the weight
      loss technique as well as electrochemical methods. Comparing the rate of
      corrosion in uninhibited and inhibited solutions as a function of temperature,
      the thermodynamic parameters of adsorption of these derivatives on mild steel
      surfaces and the kinetic parameters of the corrosion process are evaluated. These
      parameters together with information derived from electrochemical methods are
      further used to ascertain the mechanism of corrosion and mode of adsorption of
      inhibitors with intricate detail. Density functional theory (DFT) calculations
      were employed to explain the relative corrosion inhibition propensity between the
      studied mono and di quercetin derivatives. Molecular dynamics (MD) simulations
      were carried out to obtain the interaction energy between the inhibitor molecules
      and the metal surface. Results show that both derivatives, acting as mixed-type
      inhibitors, exert profound anti-corrosive influence (around 95% inhibition
      efficiency at 1 mM concentration at 313 K). Theoretical studies suggest that the
      trihydroxy chromone ring and dihydroxy phenyl ring of quercetin maintain a planar
      orientation with respect to each other and are adsorbed on the metal surface
      (mostly chemisorption).

PMID- 29446421
TI  - A monoanionic NNNN-type macrocyclic ligand for electropositive metal centers.
AB  - The coordination of a mono(amido) triamine macrocyclic ligand Me3TACD derived
      from cyclen (1,4,7,10-tetraazacyclododecane or [12]aneN4) toward electropositive
      metal centers is surveyed. This NNNN-type monoanionic macrocyclic ligand is
      capable of stabilizing a variety of metal coordination environments that are
      commonly not amenable to stable coordination spheres. Metal complexes supported
      by Me3TACD include hydrides, hydrocarbyls, silyls, and amides. Protection of one
      hemisphere of a large metal center allows, as in the case of metallocene
      scaffolds for early transition metals, deaggregation and control of reactivity.

PMID- 29446422
TI  - Basic photophysical analysis of a thermally activated delayed fluorescence
      copper(i) complex in the solid state: theoretical estimations from a polarizable
      continuum model (PCM)-tuned range-separated density functional approach.
AB  - A quantitative understanding of photophysical processes is fundamental for
      designing novel thermally activated delayed fluorescence (TADF) materials. Taking
      a Cu(pop)(pz2Bph2) crystal as a typical TADF molecular model, we computed the
      conversion and decay rates of the first excited singlet state (S1) and triplet
      state (T1) at different temperatures by employing the thermal vibration
      correlation function (TVCF) approach. For the consideration of the solid-state
      environment, a methodology, which is based on the combination of a nonempirical,
      optimally tuned range-separated hybrid functional with the polarizable continuum
      model, was applied. Our calculated results are in excellent agreement with the
      experimentally available data. It is found that the reverse intersystem crossing
      (RISC) from T1 to S1 proceeds at a rate of kRISC = 6.34 * 105 s-1 and can compete
      with the radiative decay rate (k = 3.29 * 103 s-1) and nonradiative intersystem
      crossing rate (k = 1.48 * 102 s-1) of T1 at 300 K. This implies that the S1 state
      can be repopulated from the T1 state, TADF should be observed and the TADF decay
      time was found to be tau (300 K) = 9.68 MUs by fitting calculations. In addition,
      the calculations indicate that the free rotation of the phenylene ring in the pop
      ligand can provide an important channel to energy conversion between T1 and S1.
      But, at a low temperature of T < 100 K, the situation will experience a larger
      change. The RISC rate becomes very small, kRISC ? k or kISC, and it cannot induce
      an occurrence of delayed fluorescence. As a consequence, Cu(pop)(pz2Bph2) is a
      highly attractive candidate for applications of TADF.

PMID- 29446423
TI  - Computational investigation on DNA sequencing using functionalized graphene
      nanopores.
AB  - Fast, low-cost and reliable DNA sequencing is one of the most desirable
      innovations in recent years, which can pave the way for high throughput, label
      free and inexpensive personalized genome sequencing techniques. Although graphene
      based nanopore devices hold great promise for next-generation DNA sequencing, it
      is still a challenging problem to detect different DNA sequences efficiently and
      accurately. In the present work, the translocation of four homogeneous DNA
      strands (i.e., poly(A)20, poly(C)20, poly(G)20, and poly(T)20) through the
      functionalized graphene nanopores is investigated by all-atom molecular dynamic
      simulations. Interestingly, it is found that the four types of bases could be
      identified by different ionic currents when they pass through the hydrogenated
      and hydroxylated pores. For the hydrogenated nanopore, the difference in the
      ionic current for the four bases is mainly attributed to the different
      electrostatic interactions between the base and the ion. For the hydroxylated
      nanopore, apart from the electrostatic interactions, the position of a nucleotide
      inside the nanopore and the dwell time of an ion around the nucleotide also play
      an important role in the ionic current. The present study could be helpful to
      better design a novel device for DNA sequencing in the future.

PMID- 29446424
TI  - Adsorption of amphiphilic graft copolymers in solvents selective for the grafts
      on a lyophobic surface: a coarse-grained simulation study.
AB  - The sorption of graft copolymers on surfaces attractive only for the backbone and
      its effect on the conformational behavior of adsorbed/desorbed chains in solvents
      good for the grafts and poor for the backbone was studied by coarse-grained
      computer simulations. It was found that the sorption and conformational behavior
      are very complex and are results of an intricate interplay of solvent quality
      (polymer-solvent interactions) and solvent strength (polymer-surface vs. solvent
      surface interactions). Increasing grafting density and length of grafts protect
      the backbone against adsorption, but the behavior is non-trivial. A decrease in
      solvent quality promotes the adsorption, because it lowers the overall
      solubility, but the backbone collapses and the probability of backbone-surface
      contacts decreases, which simultaneously hinders the adsorption. The results of
      simulations are presented in the form of phase diagrams depicting the decisive
      features of the conformational and sorption behavior.

PMID- 29446425
TI  - Electronic structure calculations and nonadiabatic dynamics simulations of
      excited-state relaxation of Pigment Yellow 101.
AB  - Pigment Yellow 101 (PY101) is widely used as a typical pigment due to its
      excellent excited-state properties. However, the origin of its photostability is
      still elusive. In this work, we have systematically investigated the
      photodynamics of PY101 by performing combined electronic structure calculations
      and trajectory-based nonadiabatic dynamics simulations. On the basis of the
      results, we have found that upon photoexcitation to the S1 state, PY101 undergoes
      an essentially barrierless excited-state intramolecular single proton transfer
      generating an S1 keto species. In the keto region, there is an energetically
      accessible S1/S0 conical intersection that funnels the system to the S0 state
      quickly. In the S0 state, the keto species either goes back to its trans-enol
      species through a ground-state reverse hydrogen transfer or arrives at the cis
      keto region. In addition, we have found an additional excited-state decay channel
      for the S1 enol species, which is directly linked to an S1/S0 conical
      intersection located in the enol region. This mechanism has also been confirmed
      by our dynamics simulations, in which about 54% of the trajectories decay to the
      S0 state via the enol S1/S0 conical intersection; while the remaining ones employ
      the keto S1/S0 conical intersection. The gained mechanistic information helps us
      understand the photostability of the PY101 chromophore and its variants with the
      same molecular scaffold.

PMID- 29446426
TI  - Time dependent aggregation induced emission enhancement and the study of
      molecular packing in closely related azo-phenol BODIPY species.
AB  - Fluorescent azo-phenol BODIPYs (1-3) have been obtained by the substituent (
      OCH3/-CH3) directed synthesis of ortho (L1) and para (L2-L3) azo-phenol
      aldehydes. These display aggregation caused quenching (ACQ, 1) and aggregation
      induced emission enhancement (AIEE, 2 and 3) depending on the position of azo
      relative to the phenolic hydroxyl group. An intriguing time dependent
      morphological transition from nanospheres to ordered nanorods and subsequent
      emission changes in AIEE active azo-phenol BODIPYs have been successfully
      realized by time dependent fluorescence, scanning electron (SEM), transmission
      electron (TEM) and fluorescence optical microscopy (FOM) studies. The existence
      of one-dimensional (1D) nanorods as ultimate species in these compounds (2-3) has
      been supported by crystal packing patterns. Diverse aggregated forms and
      hierarchical nanostructures have been related to variable extents of fluorescence
      enhancement. The plausible charge transfer process and its role in AIEE have been
      supported by DFT studies.

PMID- 29446427
TI  - Nickel(iii)-mediated oxidative cascades from a thiol-bearing nickel(ii) precursor
      to the nickel(iv) product.
AB  - A nickel(ii) complex, Ni(HPS2)2 (1) that contains two pendant thiols, is rapidly
      aerobically oxidized in the presence of an amine to produce a diamagnetic
      nickel(iv) complex, Ni(PS2)2 (2). This process was investigated spectroscopically
      at a temperature of -80  degrees C. Absorption spectra revealed that the
      deprotonation of one pendant thiol of 1 triggers an oxidative cascade; EPR
      findings indicate that single-spin species comprised of nickel(iii) intermediates
      are produced in the reaction solution. Possible reaction routes were examined by
      DFT calculations, in which an energy profile indicates that (i) a self-driven
      formation of 2 favors a sequential proton/electron transfer pathway; (ii)
      kinetically trapped nickel(iii) intermediates may respond to the specificity of
      the coordination of 2 in a cis-form. The overall findings help one to rationalize
      how a nickel(ii) precursor can be oxidized by O2 to a higher oxidation state.

PMID- 29446428
TI  - p-Type conductivity of hexagonal boron nitride as a dielectrically tunable
      monolayer: modulation doping with magnesium.
AB  - Hexagonal boron nitride (h-BN) is the widest band gap 2D material (>6 eV), which
      has attracted extensive attention. For exploring potential applications in
      optoelectronic devices, electrical conductivity modulation (n or p type) is of
      extreme importance. Here, we report the achievement of a large-scale and high
      quality h-BN monolayer with p-type conductivity by modulation doping of Mg using
      a low pressure chemical vapor deposition method. A large-scale monolayer h-BN
      (>10 inches) was grown by using a wound Cu foil roll on a multi-prong quartz
      fork. Magnesium nitride is used as a dopant precursor in a separate line due to
      its appropriate melting point and decomposition temperature. Density functional
      theory calculations revealed that the acceptor level introduced by Mg is almost
      pinned into the valence band and the activated holes are highly delocalized into
      the surrounding h-BN lattices. The h-BN:Mg monolayer showed a p-type conductivity
      with a considerable surface current of over 12 MUA and a hole density of 1.7 *
      1014 cm-2. The dielectrically tunable h-BN monolayer makes the fabrication of
      advanced 2D optoelectronic devices in short wavelength possible.

PMID- 29446429
TI  - Optical nano-biosensing interface via nucleic acid amplification strategy:
      construction and application.
AB  - Modern optical detection technology plays a critical role in current clinical
      detection due to its high sensitivity and accuracy. However, higher requirements
      such as extremely high detection sensitivity have been put forward due to the
      clinical needs for the early finding and diagnosing of malignant tumors which are
      significant for tumor therapy. The technology of isothermal amplification with
      nucleic acids opens up avenues for meeting this requirement. Recent reports have
      shown that a nucleic acid amplification-assisted modern optical sensing interface
      has achieved satisfactory sensitivity and accuracy, high speed and specificity.
      Compared with isothermal amplification technology designed to work completely in
      a solution system, solid biosensing interfaces demonstrated better performances
      in stability and sensitivity due to their ease of separation from the reaction
      mixture and the better signal transduction on these optical nano-biosensing
      interfaces. Also the flexibility and designability during the construction of
      these nano-biosensing interfaces provided a promising research topic for the
      ultrasensitive detection of cancer diseases. In this review, we describe the
      construction of the burgeoning number of optical nano-biosensing interfaces
      assisted by a nucleic acid amplification strategy, and provide insightful views
      on: (1) approaches to the smart fabrication of an optical nano-biosensing
      interface, (2) biosensing mechanisms via the nucleic acid amplification method,
      (3) the newest strategies and future perspectives.

PMID- 29446430
TI  - Highly stable SnO2-Fe2O3-C hollow spheres for reversible lithium storage with
      extremely long cycle life.
AB  - SnO2-Fe2O3-C triple-shell hollow nano-spheres are fabricated by combining the
      template-based sol-gel coating technique and hydrothermal method, and their
      electrochemical performance as an anode for lithium ion batteries (LIBs) is
      investigated, particularly focusing on their structural stability and long term
      cyclability. To accomplish this, same-sized SnO2 solid spheres, Fe2O3 solid
      spheres, SnO2-Fe2O3 solid spheres, SnO2-Fe2O3-C solid spheres, SnO2 hollow
      spheres and SnO2-Fe2O3 hollow spheres are prepared in a similar manner and their
      cyclic performances are compared. It is found that the as-synthesized 80 nm-sized
      SnO2-Fe2O3-C hollow sphere electrode exhibits an extraordinary reversible
      capacity (1100 mA h g-1 after 100 cycles at 200 mA g-1) and excellent long cycle
      stability (475 mA h g-1 after 1000 cycles at 2000 mA g-1), which are attributed
      to the Fe-enhanced reversibility of the Li2O reduction reaction, high electrical
      conductivity, high Li+ ion mobility, and structural stability of the carbon
      coated triple-shell hollow spheres.

PMID- 29446431
TI  - Highly diastereoselective oxa-[3+3] cyclization with C,N-cyclic azomethine imines
      via the copper-catalyzed aerobic oxygenated C[double bond, length as m-dash]C
      bond of indoles.
AB  - Herein, a copper-catalyzed highly diastereoselective aerobic oxygenated [3+3]
      cyclization of 3-substituted indoles with C,N-cyclic azomethine imines using
      oxygen as the sole oxidant under mild conditions has been developed. This
      protocol provides a simple and convenient approach for constructing [2,3]-fused
      indoline O-heterocycles bearing two pharmaceutically intriguing parts,
      tetrahydroisoquinoline and indoline. Good yields and excellent
      diastereoselectivity under mild reaction conditions were observed.

PMID- 29446432
TI  - Serum albumin hydrogels in broad pH and temperature ranges: characterization of
      their self-assembled structures and nanoscopic and macroscopic properties.
AB  - We report extended pH- and temperature-induced preparation procedures and explore
      the materials and molecular properties of different types of hydrogels made from
      human and bovine serum albumin, the major transport protein in the blood of
      mammals. We describe the diverse range of properties of these hydrogels at three
      levels: (1) their viscoelastic (macroscopic) behavior, (2) protein secondary
      structure changes during the gelation process (via ATR-FTIR spectroscopy), and
      (3) the hydrogel fatty acid (FA) binding capacity and derive from this the
      generalized tertiary structure through CW EPR spectroscopy. We describe the
      possibility of preparing hydrogels from serum albumin under mild conditions such
      as low temperatures (notably below albumin's denaturation temperature) and
      neutral pH value. As such, the proteins retain most of their native secondary
      structure. We find that all the combined data indicate a two-stage gelation
      process that is studied in detail. We summarize these findings and the explored
      dependences of the gels on pH, temperature, concentration, and incubation time by
      proposing phase diagrams for both HSA and BSA gel-states. As such, it has become
      possible to prepare gels that have the desired nanoscopic and macroscopic
      properties, which can, in future, be tested for, e.g., drug delivery
      applications.

PMID- 29446433
TI  - Asymmetric synthesis of trans-4,5-disubstituted gamma-butyrolactones involving a
      key allylboration step. First access to (-)-nicotlactone B and (-)-galbacin.
AB  - An efficient asymmetric synthesis of trans-4,5-disubstituted gamma-butyrolactones
      from aldehydes and enantioenriched gamma-carbamate alkenylboronates is reported.
      The cornerstone of this strategy is the implementation of sequential [3,3]-allyl
      cyanate rearrangement/allylboration/nucleophilic addition/cyclisation reactions.
      Diverse gamma-butyrolactones such as the flavouring compounds, (+)-trans-whiskey
      lactone and (+)-trans-cognac lactone, as well as an advanced intermediate towards
      the first synthesis of natural products, (-)-nicotlactone B and (-)-galbacin,
      have thus been obtained.

PMID- 29446434
TI  - Thermal conversion of primary alcohols to disulfides via xanthate intermediates:
      an extension to the Chugaev elimination.
AB  - Primary alcohols are converted into dialkyl disulfides via heating in situ
      generated O-alkyl S-difluoro(ethoxycarbonyl)methyl xanthates from ethyl
      bromodifluoroacetate and potassium xanthates, prepared from primary alcohols and
      carbon disulfide in the presence of KOH. The reaction mechanism is suggested as
      an alkyl C[1,3] shift followed by a radical mechanism. This extends to the
      Chugaev elimination which yields olefins. The current research provides easy
      access to dialkyl disulfides from commercially available primary alkanols.

PMID- 29446435
TI  - Aromatically functionalized pseudo-crown ethers with unusual solvent response and
      enhanced binding properties.
AB  - Conformational flexibility in the host's structure is often considered
      detrimental to its binding. Flexible pseudo-crown ethers with aromatic
      donor/acceptor groups at the chain ends, however, displayed enhanced binding
      affinity and selectivity, particularly when the direct binding interactions were
      compromised by unfavorable solvents.

PMID- 29446436
TI  - The WITS Atlas: A Black Southern African dental atlas for permanent tooth
      formation and emergence.
AB  - : Current dental maturity charts, such as the widely applied London atlas, do not
      take into consideration advanced tooth emergence and formation patterns observed
      in children of African ancestry. The result is inaccurate age estimation in
      Southern Africa, a region where there is great forensic and anthropological need
      for reliable age estimation. OBJECTIVES: To develop a population-specific atlas
      of permanent tooth emergence and formation for age estimation of Black Southern
      Africans. MATERIALS AND METHODS: Using data from a cross-sectional study of 642
      school children aged 5-20 years, panoramic radiographs taken during routine
      dental examination in a mobile treatment van were analyzed using the Demirjian
      method of eight (A-H) tooth formation stages. Tables of the stages of tooth
      development for each tooth, including the third molars, were generated separately
      for age cohorts and by sex. The most frequently occurring (modal) stage of tooth
      formation was considered the signature developmental stage for the age. The
      relationship of the third molar occlusal surfaces with occlusal tables on the
      radiographs were checked and compared with the findings recorded during intra
      oral examination. RESULTS: Comparison with the London atlas shows that at age 9.5
      years, the canine and premolar emergence are at least one year ahead and the
      third molar formation completes four years earlier in the WITS Atlas. DISCUSSION:
      Similarities in advancement in tooth formation and emergence across sub-Saharan
      Africa suggest that the WITS Atlas can be used for those populations as well.

PMID- 29446437
TI  - Effects of total fat intake on bodyweight in children.
AB  - BACKGROUND: As part of efforts to prevent childhood overweight and obesity, we
      need to understand the relationship between total fat intake and body fatness in
      generally healthy children. OBJECTIVES: To assess the effects of total fat intake
      on measures of weight and body fatness in children and young people not aiming to
      lose weight. SEARCH METHODS: For this update we revised the previous search
      strategy and ran it over all years in the Cochrane Library, MEDLINE (Ovid),
      MEDLINE (PubMed), and Embase (Ovid) (current to 23 May 2017). No language and
      publication status limits were applied. We searched the World Health Organization
      International Clinical Trials Registry Platform and ClinicalTrials.gov for
      ongoing and unpublished studies (5 June 2017). SELECTION CRITERIA: We included
      randomised controlled trials (RCTs) in children aged 24 months to 18 years, with
      or without risk factors for cardiovascular disease, randomised to a lower fat
      (30% or less of total energy (TE)) versus usual or moderate-fat diet (greater
      than 30%TE), without the intention to reduce weight, and assessed a measure of
      weight or body fatness after at least six months. We included prospective
      analytical cohort studies in these children if they related baseline total fat
      intake to weight or body fatness at least 12 months later. We duplicated
      inclusion decisions and resolved disagreement by discussion with other authors.
      DATA COLLECTION AND ANALYSIS: We extracted data on participants, interventions or
      exposures, controls and outcomes, and trial or cohort quality characteristics, as
      well as data on potential effect modifiers, and assessed risk of bias for all
      included studies. We extracted outcome data using the following time point
      ranges, when available: RCTs: baseline to six months, six to 12 months, one to
      two years, two to five years and more than five years; cohort studies: baseline
      to one year, one to two years, two to five years, five to 10 years and more than
      10 years. We planned to perform random-effects meta-analyses with relevant
      subgrouping, and sensitivity and funnel plot analyses where data allowed. MAIN
      RESULTS: We included 24 studies comprising three parallel-group RCTs (n = 1054
      randomised) and 21 prospective analytical cohort studies (about 25,059 children
      completed). Twenty-three were conducted in high-income countries. No meta
      analyses were possible, since only one RCT reported the same outcome at each time
      point range for all outcomes, and cohort studies were too heterogeneous.For the
      RCTs, concerns about imprecision and poor reporting limited our confidence in our
      findings. In addition, the inclusion of hypercholesteraemic children in two
      trials raised concerns about applicability. Lower versus usual or modified total
      fat intake may have made little or no difference to weight over a six- to twelve
      month period (mean difference (MD) -0.50 kg, 95% confidence interval (CI) -1.78
      to 0.78; 1 RCT; n = 620; low-quality evidence), nor a two- to five-year period
      (MD -0.60 kg, 95% CI -2.39 to 1.19; 1 RCT; n = 612; low-quality evidence).
      Compared to controls, lower total fat intake (30% or less TE) probably decreased
      BMI in children over a one- to two-year period (MD -1.5 kg/m2, 95% CI -2.45 to 
      0.55; 1 RCT; n = 191; moderate-quality evidence), with no other differences
      evident across the other time points (two to five years: MD 0.00 kg/m2, 95% CI 
      0.63 to 0.63; 1 RCT; n = 541; greater than five years; MD -0.10 kg/m2, 95% CI 
      0.75 to 0.55; 1 RCT; n = 576; low-quality evidence). Lower fat intake probably
      slightly reduced total cholesterol over six to 12 months compared to controls (MD
      -0.15 mmol/L, 95% CI -0.24 to -0.06; 1 RCT; n = 618; moderate-quality evidence),
      but may make little or no difference over longer time periods. Lower fat intake
      probably slightly decreased low-density lipoprotein (LDL) cholesterol over six to
      12 months (MD -0.12 mmol/L, 95% CI -0.20 to -0.04; 1 RCT; n = 618, moderate
      quality evidence) and over two to five years (MD -0.09, 95% CI -0.17 to -0.01; 1
      RCT; n = 623; moderate-quality evidence), compared to controls. However, lower
      total fat intake probably made little or no difference to HDL-C over a six- to 12
      month period (MD -0.03 mmol/L, 95% CI -0.08 to 0.02; 1 RCT; n = 618; moderate
      quality evidence), nor a two- to five-year period (MD -0.01 mmol/L, 95% CI -0.06
      to 0.04; 1 RCT; n = 522; moderate-quality evidence). Likewise, lower total fat
      intake probably made little or no difference to triglycerides in children over a
      six- to 12-month period (MD -0.01 mmol/L, 95% CI -0.08 to 0.06; 1 RCT; n = 618;
      moderate-quality evidence). Lower versus usual or modified fat intake may make
      little or no difference to height over more than five years (MD -0.60 cm, 95% CI 
      2.06 to 0.86; 1 RCT; n = 577; low-quality evidence).Over half the cohort analyses
      that reported on primary outcomes suggested that as total fat intake increases,
      body fatness measures may move in the same direction. However, heterogeneous
      methods and reporting across cohort studies, and predominantly very low-quality
      evidence, made it difficult to draw firm conclusions and true relationships may
      be substantially different. AUTHORS' CONCLUSIONS: We were unable to reach firm
      conclusions. Limited evidence from three trials that randomised children to a
      lower total fat intake (30% or less TE) versus usual or modified fat intake, but
      with no intention to reduce weight, showed small reductions in body mass index,
      total- and LDL-cholesterol at some time points with lower fat intake compared to
      controls, and no consistent differences in effects on weight, high-density
      lipoprotein (HDL) cholesterol or height. Associations in cohort studies that
      related total fat intake to later measures of body fatness in children were
      inconsistent and the quality of this evidence was mostly very low. Twenty-three
      out of 24 included studies were conducted in high-income countries, and may not
      be applicable in low- and middle-income settings. High-quality, longer-term
      studies are needed, that include low- and middle-income settings and look at both
      possible benefits and risks.

PMID- 29446438
TI  - Three-dimensional (3D) geometric morphometric analysis of human premolars to
      assess sexual dimorphism and biological ancestry in Australian populations.
AB  - OBJECTIVES: This study aimed to investigate size and shape variation of human
      premolars between Indigenous Australians and Australians of European ancestry,
      and to assess whether sex and ancestry could be differentiated between these
      groups using 3D geometric morphometrics. MATERIALS AND METHODS: Seventy dental
      casts from each group, equally subdivided by sex, were scanned using a structured
      light scanner. The 3D meshes of upper and lower premolars were processed using
      geometric morphometric methods. Seventy-two landmarks were recorded for upper
      premolars and 50 landmarks for lower premolars. For each tooth type, two-way
      ANOVA was used to assess group differences in centroid size. Shape variations
      were explored using principal component analysis and visualized using 3D
      morphing. Two-way Procrustes ANOVA was applied to test group differences for
      ancestry and sex, and a "leave-one-out" discriminant function was applied to
      assess group assignment. RESULTS: Centroid size and shape did not display
      significant difference between the sexes. Centroid size was larger in Indigenous
      Australians for upper premolars and lower second premolars compared to the
      Australians of European ancestry. Significant shape variation was noted between
      the two ancestral groups for upper premolars and the lower first premolar.
      Correct group assignment of individual teeth to their ancestral groups ranged
      between 80.0 and 92.8% for upper premolars and 60.0 and 75.7% for lower
      premolars. DISCUSSION: Our findings provide evidence of significant size and
      shape variation in human premolars between the two ancestral groups. High
      classification rates based on shape analysis of upper premolars highlight
      potential application of geometric morphometrics in anthropological,
      bioarcheological and forensic contexts.

PMID- 29446439
TI  - Vision screening for correctable visual acuity deficits in school-age children
      and adolescents.
AB  - BACKGROUND: Although the benefits of vision screening seem intuitive, the value
      of such programmes in junior and senior schools has been questioned. In addition
      there exists a lack of clarity regarding the optimum age for screening and
      frequency at which to carry out screening. OBJECTIVES: To evaluate the
      effectiveness of vision screening programmes carried out in schools to reduce the
      prevalence of correctable visual acuity deficits due to refractive error in
      school-age children. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials
      Register) (2017, Issue 4); Ovid MEDLINE; Ovid Embase; the ISRCTN registry;
      ClinicalTrials.gov and the ICTRP. The date of the search was 3 May 2017.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs), including
      cluster-randomised trials, that compared vision screening with no vision
      screening, or compared interventions to improve uptake of spectacles or
      efficiency of vision screening. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened search results and extracted data. Our pre-specified
      primary outcome was uncorrected, or suboptimally corrected, visual acuity deficit
      due to refractive error six months after screening. Pre-specified secondary
      outcomes included visual acuity deficit due to refractive error more than six
      months after screening, visual acuity deficit due to causes other than refractive
      error, spectacle wearing, quality of life, costs, and adverse effects. We graded
      the certainty of the evidence using GRADE. MAIN RESULTS: We identified seven
      relevant studies. Five of these studies were conducted in China with one study in
      India and one in Tanzania. A total of 9858 children aged between 10 and 18 years
      were randomised in these studies, 8240 of whom (84%) were followed up between one
      and eight months after screening. Overall we judged the studies to be at low risk
      of bias. None of these studies compared vision screening for correctable visual
      acuity deficits with not screening.Two studies compared vision screening with the
      provision of free spectacles versus vision screening with no provision of free
      spectacles (prescription only). These studies provide high-certainty evidence
      that vision screening with provision of free spectacles results in a higher
      proportion of children wearing spectacles than if vision screening is accompanied
      by provision of a prescription only (risk ratio (RR) 1.60, 95% confidence
      interval (CI) 1.34 to 1.90; 1092 participants). The studies suggest that if
      approximately 250 per 1000 children given vision screening plus prescription only
      are wearing spectacles at follow-up (three to six months) then 400 per 1000 (335
      to 475) children would be wearing spectacles after vision screening and provision
      of free spectacles. Low-certainty evidence suggested better educational
      attainment in children in the free spectacles group (adjusted difference 0.11 in
      standardised mathematics score, 95% CI 0.01 to 0.21, 1 study, 2289 participants).
      Costs were reported in one study in Tanzania in 2008 and indicated a relatively
      low cost of screening and spectacle provision (low-certainty evidence). There was
      no evidence of any important effect of provision of free spectacles on
      uncorrected visual acuity (mean difference -0.02 logMAR (95% CI adjusted for
      clustering -0.04 to 0.01) between the groups at follow-up (moderate-certainty
      evidence). Other pre-specified outcomes of this review were not reported.Two
      studies explored the effect of an educational intervention in addition to vision
      screening on spectacle wear. There was moderate-certainty evidence of little
      apparent effect of the education interventions investigated in these studies in
      addition to vision screening, compared to vision screening alone for spectacle
      wearing (RR 1.11, 95% CI 0.95 to 1.31, 1 study, 3177 participants) or related
      outcome spectacle purchase (odds ratio (OR) 0.84, 95% CI 0.55 to 1.31, 1 study,
      4448 participants). Other pre-specified outcomes of this review were not
      reported.Three studies compared vision screening with ready-made spectacles
      versus vision screening with custom-made spectacles. These studies provide
      moderate-certainty evidence of no clinically meaningful differences between the
      two types of spectacles. In one study, mean logMAR acuity in better and worse eye
      was similar between groups: mean difference (MD) better eye 0.03 logMAR, 95% CI
      0.01 to 0.05; 414 participants; MD worse eye 0.06 logMAR, 95% CI 0.04 to 0.08;
      414 participants). There was high-certainty evidence of no important difference
      in spectacle wearing (RR 0.98, 95% CI 0.91 to 1.05; 1203 participants) between
      the two groups and moderate-certainty evidence of no important difference in
      quality of life between the two groups (the mean quality-of-life score measured
      using the National Eye Institute Refractive Error Quality of Life scale 42 was
      1.42 better (1.04 worse to 3.90 better) in children with ready-made spectacles (1
      study of 188 participants). Although none of the studies reported on costs
      directly, ready-made spectacles are cheaper and may represent considerable cost
      savings for vision screening programmes in lower income settings. There was low
      certainty evidence of no important difference in adverse effects between the two
      groups. Adverse effects were reported in one study and were similar between
      groups. These included blurred vision, distorted vision, headache,
      disorientation, dizziness, eyestrain and nausea. AUTHORS' CONCLUSIONS: Vision
      screening plus provision of free spectacles improves the number of children who
      have and wear the spectacles they need compared with providing a prescription
      only. This may lead to better educational outcomes. Health education
      interventions, as currently devised and tested, do not appear to improve
      spectacle wearing in children. In lower-income settings, ready-made spectacles
      may provide a useful alternative to expensive custom-made spectacles.

PMID- 29446440
TI  - Mechanical implications of the mandibular coronoid process morphology in
      Neandertals.
AB  - OBJECTIVES: Among the diagnostic features of the Neandertal mandible are the
      broad base of the coronoid process and its straight posterior margin. The
      adaptive value of these (and other) anatomical features has been linked to the
      Neandertal's need to cope with a large gape. The present study aims to test this
      hypothesis with regard to the morphology of the coronoid process. MATERIALS AND
      METHODS: This admittedly simple, intuitive hypothesis was tested here via a
      comparative finite-element study of the primitive versus modified state of the
      coronoid process, using two-dimensional models of the mandible. RESULTS: Our
      simulations demonstrate that a large gape has an unfavorable effect on the
      primitive state of the coronoid process: the diagonal, almost horizontal,
      component of the temporalis muscle resultant (relative to the long axis of the
      coronoid process) bends the process in the sagittal plane. Furthermore, we show
      that the modification of the coronoid process morphology alone reduces the
      process' bending in a wide gape increasing the compression to tension ratio.
      DISCUSSION: These results provide indirect evidence in support of the hypothesis
      that the modification of the coronoid process in Neandertals is necessary for
      enabling their mandible to cope with a large gape.

PMID- 29446441
TI  - OsPIN2, which encodes a member of the auxin efflux carrier proteins, is involved
      in root elongation growth and lateral root formation patterns via the regulation
      of auxin distribution in rice.
AB  - Auxin flow is important for different root developmental processes such as root
      formation, emergence, elongation and gravitropism. However, the detailed
      information about the mechanisms regulating the auxin flow is less well
      understood in rice. We characterized the auxin transport-related mutants, Ospin
      formed2-1 (Ospin2-1) and Ospin2-2, which exhibited curly root phenotypes and
      altered lateral root formation patterns in rice. The OsPIN2 gene encodes a member
      of the auxin efflux carrier proteins that possibly regulates the basipetal auxin
      flow from the root tip toward the root elongation zone. According to DR5-driven
      GUS expression, there is an asymmetric auxin distribution in the mutants that
      corresponded with the asymmetric cell elongation pattern in the mutant root tip.
      Auxin transport inhibitor, N-1-naphthylphthalamic acid and Ospin2-1 Osiaa13
      double mutant rescued the curly root phenotype indicating that this phenotype
      results from a defect in proper auxin distribution. The typical curly root
      phenotype was not observed when Ospin2-1 was grown in distilled water as an
      alternative to tap water, although higher auxin levels were found at the root tip
      region of the mutant than that of the wild-type. Therefore, the lateral root
      formation zone in the mutant was shifted basipetally compared with the wild-type.
      These results reflect that an altered auxin flow in the root tip region is
      responsible for root elongation growth and lateral root formation patterns in
      rice.

PMID- 29446442
TI  - Characterization of source plasma from self-identified vaccinated or convalescent
      donors during the 2009 H1N1 pandemic.
AB  - BACKGROUND: Influenza immune globulin, manufactured from plasma of convalescent
      or vaccinated donors has been proposed as a potential therapy for severe
      influenza. In 2009, a program was initiated to collect plasma from donors who
      self-identified as having had H1N1 influenza or having received the H1N1 pandemic
      vaccine. The goal of this study was to determine the efficiency of donor
      screening by self-identification without antibody testing, and to evaluate
      demographic predictors of high-titer donations. STUDY DESIGN AND METHODS: Plasma
      samples from self-identified or control donors were randomly selected to evaluate
      hemagglutination inhibition (HAI) antibody responses. HAI titers were correlated
      with donor age, gender, location, and influenza exposure history. RESULTS: Both
      self-identified vaccinated and convalescent donor groups had higher geometric
      mean titers (GMTs) against A/California/07/2009 (H1N1) virus compared to the
      control donors (39.9, 24, and 8.5, respectively). The proportion of samples with
      titers >=64 in vaccinated, convalescent, and control donors were 54%, 37%, and
      10%, respectively. Donations with titers <=16 were predominant in control donors
      (80%) and substantial in convalescent (47%) and vaccinated (40%) donors. Titers
      did not correlate with donor age, gender, or geographical location. GMTs for
      vaccinated donors were significantly higher than for convalescent donors and in
      both groups significantly higher than in the control. CONCLUSION: Targeted
      collection of plasma containing high levels of anti-influenza antibodies from
      self-identified donors was effective, but could be further improved by reducing
      the number of low-titer donations. More selective donor screening and/or testing
      for influenza antibodies could increase the potency of an influenza antibody-rich
      immune globulin (FLUIGIV).

PMID- 29446443
TI  - Association of killer cell immunoglobulin-like receptors with spontaneous
      clearance of hepatitis C virus in the Chinese population.
AB  - BACKGROUND: Natural killer (NK) cells are critical components in innate immune
      response to viral infection. Killer cell immunoglobulin-like receptors (KIRs) are
      involved in regulating the balance of activation or inhibitory function of NK
      cells. However, the association of KIRs with the spontaneous clearance of
      hepatitis C virus (HCV) remains unclear in the Chinese population. STUDY DESIGN
      AND METHODS: A total of 407 HCV-seropositive voluntary blood donors were
      recruited, including 203 with spontaneous viral clearance and 204 with chronic
      infection. The presence of KIR genes was detected individually by polymerase
      chain reaction with sequence-specific primers. Data of HLA and interleukin-28B
      (IL28B) genotypes were extracted from our previous study. RESULTS: Our results
      showed that KIR2DL2, 2DS2, 2DL2/2DL3, and 2DL5A-/2DL5B+ were more frequent in
      subjects with HCV clearance than those with chronic infection (odds ratio [OR],
      1.640, p = 0.034; OR, 1.664, p = 0.032; OR, 1.636, p = 0.040; and OR, 2.601, p =
      0.012, respectively). Multivariate logistic regression analysis showed that
      KIR2DL5A-/2DL5B+ associated with HCV clearance (OR, 2.448, p = 0.027),
      independent of sex, IL28B, and other KIRs. In contrast, KIR2DL3/2DL3 (OR, 0.610,
      p = 0.034) as well as 2DL3/2DL3+HLA-C1 or C1C1 (OR, 0.580, p = 0.017; and OR,
      0.639, p = 0.025, respectively) was found associated with chronic HCV infection.
      The presence of the homozygous KIR2DL3 with or without its HLA ligand increased
      the OR of developing chronic HCV infection in the context of IL28B. CONCLUSIONS:
      In this study we identified KIR2DL5A-/2DL5B+ associated with HCV spontaneous
      clearance, while KIR2DL3/2DL3, 2DL3/2DL3+HLA-C1, or C1C1 associated with chronic
      infection. Our study highlighted the fact that the roles of KIR and KIR-HLA
      contributed to the control of HCV infection by innate immune responses.

PMID- 29446445
TI  - Lenograstim 5 ug/kg is not superior to biosimilar filgrastim 10 ug/kg in lymphoma
      patients undergoing peripheral blood stem cell mobilization after chemotherapy:
      preliminary results from a prospective randomized study.
AB  - BACKGROUND: Randomized trials comparing chemomobilization efficiency between
      lenograstim and biosimilar filgrastim are lacking. Our previous retrospective
      study suggested that lenograstim could be more effective than biosimilar
      filgrastim when used at the same conventional dosage (5 ug/kg) only in lymphoma
      patients undergoing peripheral blood stem cell mobilization. We planned a
      prospective randomized study comparing lenograstim 5 ug/kg with biosimilar
      filgrastim 10 ug/kg to verify the hypothesis of lenograstim superiority even at
      half the dosage (stress test). Herein we report data after enrolling 60% of
      planned patients. STUDY DESIGN AND METHODS: From October 2014 to November 2017, a
      total of 42 of 70 planned patients with lymphoma were randomly assigned to
      receive lenograstim 5 ug/kg (21) or biosimilar filgrastim 10 ug/kg (21). Patients
      were stratified according to treatment line at the time of mobilization (1 or
      >=2). Primary endpoint was the rate of achievement of the CD34+ cell collection
      target dose (>= 4 * 106 /kg). An improvement by 23% was expected to validate the
      hypothesis of lenograstim superiority. RESULTS: The two cohorts were balanced for
      all the baseline features. We observed an identical rate of patients able to
      reach the targeted CD34+ cell dose and of mobilization failures (90.4 and 4.8% in
      both cohorts) and a perfect equivalence in any of the secondary collection
      outcomes. The hypothesis of lenograstim superiority was not corroborated at
      interim analysis. CONCLUSION: Lenograstim at conventional dosage has failed to
      demonstrate its superiority over biosimilar filgrastim at double the dosage at
      interim analysis in their first head-to-head trial.

PMID- 29446444
TI  - Extracorporeal photopheresis as second-line therapy for patients with acute graft
      versus-host disease: does the number of cells treated matter?
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) has demonstrated efficacy as
      second-line treatment for steroid-refractory (SR) acute graft-versus-host disease
      (aGVHD). The aim of our study was to analyze whether the amount of ECP-treated
      cells in patients with SR, aGVHD has an impact on response at 1 month. STUDY
      DESIGN AND METHODS: Data on white blood cells, lymphocytes, monocytes,
      mononuclear cells, and neutrophils, including absolute counts and counts per
      kilogram of body weight in ECP products from patients with aGVHD, were collected.
      For each cell population, the median dose per single ECP and the cumulative doses
      collected during the first week and the first month of treatment were compared
      with the response to ECP. RESULTS: In total, 99 patients underwent 1215 ECP
      procedures. Overall response was defined as a complete response if all signs of
      aGVHD resolved or a partial response if greater than 50% resolution was reached
      without other, additional immunosuppression. An overall response was obtained by
      75% of patients, including 53% complete responses. Univariate analysis showed a
      correlation of lymphocytes and mononuclear cells/kg body weight for a single
      procedure and overall response. In logistic regression analysis, no tested
      variable had an influence on response. In receiver operating characteristic curve
      analysis, cutoffs of 8.4 * 106 /kg body weight lymphocytes and 13.9 * 106 /kg
      body weight mononuclear cells were associated with an overall response to ECP at
      1 month with 75% sensitivity. CONCLUSION: Our results in patients with steroid
      refractory aGVHD confirm that response rates to ECP are high and that certain
      cutoff values for lymphocytes and mononuclear cells/kg body weight in each
      individual procedure can predict an overall response to ECP at 1 month.

PMID- 29446446
TI  - Telemedicine in otolaryngology outpatient setting-single Center Head and Neck
      Surgery experience.
AB  - OBJECTIVES/HYPOTHESIS: We present our experience with telemedicine visits in an
      otolaryngology outpatient setting within our institution's Center for Head and
      Neck Surgery. STUDY DESIGN: Retrospective chart review. METHODS: A review of
      telemedicine outpatient encounters examining patient demographics, visit type,
      and wait times was conducted. Internet-based navigation applications were used to
      calculate travel distance and estimate commute time to our clinic. Patient survey
      responses were reviewed. RESULTS: Two hundred fifty telemedicine encounters were
      reviewed between December 2015 and June 2017. The average age of patients was 50
      years (range, 4-87 years). Patients waited an average of 10 minutes for their
      telemedicine appointments and avoided an average estimated commute time of 78
      minutes (64 miles). The majority of visits were postoperative encounters (70%).
      Clinical follow-up of recent results or nonpostoperative complaints accounted for
      the remaining 30% of visits. All patients were offered a post-telemedicine
      survey, and 78 (31%) completed the survey. Of the respondents, 95% of patients
      reported that they were satisfied with their visit. Among patients who were
      dissatisfied, wait time and technical issues were cited as reasons. CONCLUSIONS:
      With appropriate patient selection, telemedicine is an effective way to safely
      conduct outpatient clinic visits while maintaining high patient satisfaction. It
      can be particularly useful for institutions with large catchment areas to
      minimize travel times and increase ease of communication. LEVEL OF EVIDENCE: 4.
      Laryngoscope, 128:2072-2075, 2018.

PMID- 29446448
TI  - Knowledge translation in transfusion medicine. Part 2: Selecting the knowledge
      and identifying the barriers.

PMID- 29446447
TI  - Individualized prediction of seizure relapse and outcomes following antiepileptic
      drug withdrawal after pediatric epilepsy surgery.
AB  - The objective of this study was to create a clinically useful tool for
      individualized prediction of seizure outcomes following antiepileptic drug
      withdrawal after pediatric epilepsy surgery. We used data from the European
      retrospective TimeToStop study, which included 766 children from 15 centers, to
      perform a proportional hazard regression analysis. The 2 outcome measures were
      seizure recurrence and seizure freedom in the last year of follow-up. Prognostic
      factors were identified through systematic review of the literature. The
      strongest predictors for each outcome were selected through backward selection,
      after which nomograms were created. The final models included 3 to 5 factors per
      model. Discrimination in terms of adjusted concordance statistic was 0.68 (95%
      confidence interval [CI] 0.67-0.69) for predicting seizure recurrence and 0.73
      (95% CI 0.72-0.75) for predicting eventual seizure freedom. An online prediction
      tool is provided on www.epilepsypredictiontools.info/ttswithdrawal. The presented
      models can improve counseling of patients and parents regarding postoperative
      antiepileptic drug policies, by estimating individualized risks of seizure
      recurrence and eventual outcome.

PMID- 29446449
TI  - Opioid prescribing patterns among otolaryngologists: Crucial insights among the
      medicare population.
AB  - OBJECTIVES/HYPOTHESIS: There has been growing recognition of the roles
      prescription drug misuse and diversion play in facilitating the ongoing opioid
      epidemic. Our objective was to evaluate opioid prescription patterns among
      practicing otolaryngologists. STUDY DESIGN: Retrospective review of a CMS
      database. METHODS: Medicare Part D beneficiary data (2015) were accessed for a
      list of otolaryngologists. Opioid prescription rates, amount, and supply were
      calculated. Factors including board certification, experience, gender, and
      location were obtained for the 9,068 unique otolaryngologists represented in this
      dataset. RESULTS: In 2015, otolaryngologists wrote 133,779 opioid prescriptions
      for 922,806 days (6.9 days/per prescription). The majority was for hydrocodone
      acetaminophen (64.0%). Most otolaryngologists (51.2%) prescribed <= 10 opioids;
      6.1% offered > 50 opioid prescriptions. Men wrote more prescriptions on average.
      Opioid prescription rates were greatest in the Midwest (4.6%) and least in the
      Northeast (1.8%), and the highest/lowest rates were in Delaware (8.6%) and New
      York (1.3%). Midcareer (11 -20 years) otolaryngologists were most likely to write
      >50 prescriptions. The opioid prescription rate declined with greater experience.
      CONCLUSIONS: Opioid prescriptions written by otolaryngologists may play a
      significant role in the availability of these agents, as otolaryngologists wrote
      nearly 1 million days worth of opioids to Medicare beneficiaries in 2015.
      Although the majority of otolaryngologists write fewer than 11 prescriptions
      annually, those writing more prescriptions also write lengthier courses. There is
      significant geographic variation in prescribing patterns, highlighting a lack of
      consensus, and midcareer otolaryngologists are more aggressive in offering
      opioids. These findings highlight an urgent need for strengthening educational
      resources aimed at minimizing unnecessary prescriptions. LEVEL OF EVIDENCE: NA.
      Laryngoscope, 128:1576-1581, 2018.

PMID- 29446450
TI  - Comparison of physical chewing measures to consumer typed Mouth Behavior.
AB  - : The purpose of this study was to investigate the hypotheses that when presented
      with foods that could be chewed in different ways, (1) are participants jaw
      movements and chewing sequence measures correlated with Mouth Behavior (MB)
      group, as measured by the JBMB typing tool? (2) can MB group membership can be
      predicted from jaw movement and chewing sequence measures? One hundred subjects
      (69 female and 31 male, mean age 27 +/- 7.7 years) were given four different
      foods (Mentos, Walkers, Cheetos Puffs, Twix) and video recordings of their jaw
      movements made. Twenty-nine parameters were calculated on each chewing sequence
      with 27 also calculated for the first half and second half of chewing sequence.
      Subjects were assigned to a MB group using the JBMB typing tool which gives four
      MB groups ("Chewers," "Crunchers," "Smooshers," and "Suckers"). The differences
      between individual chewing parameters and MB group were assessed with analysis of
      variance which showed only small differences in average chewing parameters
      between the MB groups. By using discriminant analysis, it was possible to
      partially discriminate between MB groups based on changes in their chewing
      parameters between foods with different material properties and stages of the
      chewing. A 19-variable model correctly predicted 68% of the subjects' membership
      of a MB group. This partially confirms our first hypothesis that when presented
      with foods that could be chewed in different ways participants will use a chewing
      sequence and jaw movements that correlate with their MB as measured by the JBMB
      typing tool. PRACTICAL APPLICATIONS: The way consumers chew their food has an
      impact on their texture perception of that food. While there is a wide range of
      chewing behaviors between consumers, they can be grouped into broad categories to
      better target both product design and product testing by sensory panel. In this
      study, consumers who were grouped on their texture preference (MB group) had jaw
      movements, when chewing a range of foods, which partially reflected group
      membership. Therefore, while MB group membership could not be predicted from jaw
      movement measurements, there were similarities in jaw movements within the
      members of the groups. A better understanding of how jaw movement during chewing
      relates to consumer sensory perception would aid in new solid product design with
      controlled textural attributes.

PMID- 29446451
TI  - Practical data collection and extraction for big data applications in
      radiotherapy.
AB  - The capture of high-quality treatment data and outcomes is necessary in order to
      learn from our clinical experiences with big data analytics. In radiotherapy,
      there are several practical challenges to overcome. Practical aspects of data
      collection are discussed pointing to a need for a culture change in clinical
      practice to one that captures structured patient-related data in routine care in
      a prospective manner. Radiation dosimetry and the contoured anatomy must also be
      captured routinely to represent the best estimate of delivered radiation. The
      quality and integrity present in the data are critical which poses opportunities
      to introduce electronic validity checking to improve them. Similarly, data
      completeness and methods and technology to improve the efficiency and sufficiency
      of data capture can be introduced. In the manuscript, the types of clinical data
      are discussed including patient reports, images, biospecimens, treatments, and
      symptom management. With a data-driven culture, the realization of a learning
      health system is possible unlocking the potential of big data and its influence
      on clinical decision-making and hypothesis generation.

PMID- 29446452
TI  - Development of Children's Use of External Reminders for Hard-to-Remember
      Intentions.
AB  - This study explored under what conditions young children would set reminders to
      aid their memory for delayed intentions. A computerized task requiring
      participants to carry out delayed intentions under varying levels of cognitive
      load was presented to 63 children (aged between 6.9 and 13.0 years old). Children
      of all ages demonstrated metacognitive predictions of their performance that were
      congruent with task difficulty. Only older children, however, set more reminders
      when they expected their future memory performance to be poorer. These results
      suggest that most primary school-aged children possess metacognitive knowledge
      about their prospective memory limits, but that only older children may be able
      to exercise the metacognitive control required to translate this knowledge into
      strategic reminder setting.

PMID- 29446453
TI  - A Semiempirical Approach to the Determination of Daily Erythemal Doses.
AB  - The maintenance of ground-based instruments to measure the incidence of
      ultraviolet radiation (UVR) from the Sun demands strict and well-developed
      procedures. A piece of equipment can be out of service for a couple of weeks or
      months for calibration, repair or even the improvement of the facilities where it
      has been set up. However, the replacement of an instrument in such circumstances
      can be logistically and financially prohibitive. On the other hand, the lack of
      data can jeopardize a long-term experiment. In this study, we introduce a
      semiempirical approach to the determination of the theoretical daily erythemal
      dose (DEDt ) for periods of instrumental absence in a tropical site. The approach
      is based on 5 years of ground-based measurements of daily erythemal dose (DED)
      linearly correlated with parameters of total ozone column (TOC) and reflectivity
      (RPC ) from the Ozone Monitoring Instrument (OMI) and the cosine of solar zenith
      angle at noon (SZAn ). Seventeen months of missing ground-based data were
      replaced with DEDt , leading to a complete 5-year series of data. The lowest and
      the highest values of typical DED were 2411 +/- 322 J m-2 (1sigma) (winter) and
      5263 +/- 997 J m-2 (summer). The monthly integrated erythemal dose (mED) varied
      from 59 kJ m-2 (winter) to 162 kJ m-2 (summer). Both of them depended mainly on
      cos(SZAn ) and RPC . The 12-month integrated erythemal dose (12-ED) ranged from
      1350 kJ m-2 to 1546 kJ m-2 , but it can depend significantly on other atmospheric
      parameter (maybe aerosols) not explicitly considered here.

PMID- 29446454
TI  - Rituximab as a therapeutic consideration for refractory eosinophilic fasciitis.

PMID- 29446455
TI  - Uncultivated stromal vascular fraction is equivalent to adipose-derived stem and
      stromal cells on porous polyurethrane scaffolds forming adipose tissue in vivo.
AB  - OBJECTIVES/HYPOTHESIS: To find an alternative approach to contemporary techniques
      in tissue augmentation and reconstruction, tissue engineering strategies aim to
      involve adipose-derived stem and stromal cells (ASCs) harboring a strong
      differentiation potential into various tissue types such as bone, cartilage, and
      fat. STUDY DESIGN: Animal research. METHODS: The stromal vascular fraction (SVF)
      was used directly as a cell source to provide a potential alternative to
      contemporary ASC-based adipose tissue engineering. Seeded in TissuCol fibrin, we
      applied ASCs or SVF cells to porous, degradable polyurethane (PU) scaffolds.
      RESULTS: We successfully demonstrated the in vivo generation of volume-stable,
      well-vascularized PU-based constructs containing host-derived mature fat pads.
      Seeded human stem cells served as modulators of host-cell migration rather than
      differentiating themselves. We further demonstrated that preliminary culture of
      SVF cells was not necessary. CONCLUSIONS: Our results bring adipose tissue
      engineering, together with automated processing devices, closer to clinical
      applicability. The time-consuming and cost-intensive culture and induction of the
      ASCs is not necessary. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E206-E213, 2018.

PMID- 29446456
TI  - Lack of mitochondrial thioredoxin o1 is compensated by antioxidant components
      under salinity in Arabidopsis thaliana plants.
AB  - In a changing environment, plants are able to acclimate to new conditions by
      regulating their metabolism through the antioxidant and redox systems involved in
      the stress response. Here, we studied a mitochondrial thioredoxin in wild-type
      (WT) Arabidopis thaliana and two Attrxo1 mutant lines grown in the absence or
      presence of 100 mM NaCl. Compared to WT plants, no evident phenotype was observed
      in the mutant plants under control condition, although they had higher number of
      stomata, loss of water, nitric oxide and carbonyl protein contents as well as
      higher activity of superoxide dismutase (SOD) and catalase enzymes than WT
      plants. Under salinity, the mutants presented lower water loss and higher
      stomatal closure, H2 O2 and lipid peroxidation levels accompanied by higher
      enzymatic activity of catalase and the different SOD isoenzymes compared to WT
      plants. These inductions may collaborate in the maintenance of plant integrity
      and growth observed under saline conditions, possibly as a way to compensate the
      lack of TRXo1. We discuss the potential of TRXo1 to influence the development of
      the whole plant under saline conditions, which have great value for the agronomy
      of plants growing under unfavorable environment.

PMID- 29446457
TI  - Toward a multifactorial model of expertise: beyond born versus made.
AB  - The debate over the origins of individual differences in expertise has raged for
      over a century in psychology. The "nature" view holds that expertise reflects
      "innate talent"-that is, genetically determined abilities. The "nurture" view
      counters that, if talent even exists, its effects on ultimate performance are
      negligible. While no scientist takes seriously a strict nature-only view of
      expertise, the nurture view has gained tremendous popularity over the past
      several decades. This environmentalist view holds that individual differences in
      expertise reflect training history, with no important contribution to ultimate
      performance by innate ability ("talent"). Here, we argue that, despite its
      popularity, this view is inadequate to account for the evidence concerning the
      origins of expertise that has accumulated since the view was first proposed. More
      generally, we argue that the nature versus nurture debate in research on
      expertise is over-or certainly should be, as it has been in other areas of
      psychological research for decades. We describe a multifactorial model for
      research on the nature and nurture of expertise, which we believe will provide a
      progressive direction for future research on expertise.

PMID- 29446458
TI  - Clinical criteria for CT scan evaluation of upper digestive tract fishbone.
AB  - OBJECTIVES: To establish clinical criteria for performing computed tomography
      scan for suspected upper digestive tract fishbone. METHODS: This is a prospective
      study of all adult patients referred to the otolaryngology emergency department
      at our medical center for suspected fishbone in the upper digestive tract after
      no fishbone was seen on physical examination. The patients were divided into two
      groups: 1) The first was a high clinical suspicion group, which included patients
      with at least one of the following criteria: drooling, accumulation of saliva in
      the sinus piriformis, fever, referral 24 hours after the ingestion with
      worsening/continuing symptoms, and readmission. These patients underwent
      nonenhanced CT scan (NECT) of the neck. 2) The second was a low clinical
      suspicion group, which included patients discharged with no NECT performed. These
      patients were followed at 1 week and 3 months. RESULTS: One hundred and fourteen
      patients were included in the study; the median age was 41 years. Half of the
      patients arrived at the emergency department within 7 hours. There were no false
      negatives. The negative predictive value and sensitivity were 100%. Positive
      predictive value and specificity were 28.5% and 65%, respectively. Referral to
      the emergency department 24 hours after the ingestion with continuing symptoms
      had the highest false positive rate. CONCLUSIONS: Our clinical criteria score for
      excluding foreign body fishbone in the upper aerodigestive tract was established.
      According to this score, a NECT can be spared in about 75% of all cases, thus
      reducing unnecessary ionizing radiation, stay at the emergency department, and
      costs with a very high NPV of almost 99%. LEVEL OF EVIDENCE: 4. Laryngoscope,
      2467-2472, 2018.

PMID- 29446460
TI  - A multivariate ecogeographic analysis of macaque craniodental variation.
AB  - OBJECTIVES: To infer the ecogeographic conditions that underlie the evolutionary
      diversification of macaques, we investigated the within- and between-species
      relationships of craniodental dimensions, geography, and environment in extant
      macaque species. We studied evolutionary processes by contrasting
      macroevolutionary patterns, phylogeny, and within-species associations. MATERIALS
      AND METHODS: Sixty-three linear measurements of the permanent dentition and skull
      along with data about climate, ecology (environment), and spatial geography were
      collected for 711 specimens of 12 macaque species and analyzed by a multivariate
      approach. Phylogenetic two-block partial least squares was used to identify
      patterns of covariance between craniodental and environmental variation.
      Phylogenetic reduced rank regression was employed to analyze spatial clines in
      morphological variation. RESULTS: Between-species associations consisted of two
      distinct multivariate patterns. The first represents overall craniodental size
      and is negatively associated with temperature and habitat, but positively with
      latitude. The second pattern shows an antero-posterior tooth size contrast
      related to diet, rainfall, and habitat productivity. After controlling for
      phylogeny, however, the latter dimension was diminished. Within-species analyses
      neither revealed significant association between morphology, environment, and
      geography, nor evidence of isolation by distance. DISCUSSION: We found evidence
      for environmental adaptation in macaque body and craniodental size, primarily
      driven by selection for thermoregulation. This pattern cannot be explained by the
      within-species pattern, indicating an evolved genetic basis for the between
      species relationship. The dietary signal in relative tooth size, by contrast, can
      largely be explained by phylogeny. This cautions against adaptive interpretations
      of phenotype-environment associations when phylogeny is not explicitly modelled.

PMID- 29446462
TI  - Fostering international collaboration to achieve the Sustainable Development
      Goals by mobilizing resources -My experience in the World Health Organization
      Nursing and Midwife Scholar Programme.

PMID- 29446459
TI  - The challenge of converting Gram-positive-only compounds into broad-spectrum
      antibiotics.
AB  - Multidrug resistant Gram-negative bacterial infections are on the rise, and there
      is a lack of new classes of drugs to treat these pathogens. This drug shortage is
      largely due to the challenge of finding antibiotics that can permeate and persist
      inside Gram-negative species. Efforts to understand the molecular properties that
      enable certain compounds to accumulate in Gram-negative bacteria based on
      retrospective studies of known antibiotics have not been generally actionable in
      the development of new antibiotics. A recent assessment of the ability of >180
      diverse small molecules to accumulate in Escherichia coli led to predictive
      guidelines for compound accumulation in E. coli. These "eNTRy rules" state that
      compounds are most likely to accumulate if they contain a nonsterically
      encumbered ionizable Nitrogen (primary amines are the best), have low Three
      dimensionality (globularity <= 0.25), and are relatively Rigid (rotatable bonds
      <= 5). In this review, we look back through 50+ years of antibacterial research
      and 1000s of derivatives and assess this historical data set through the lens of
      these predictive guidelines. The results are consistent with the eNTRy rules,
      suggesting that the eNTRy rules may provide an actionable and general roadmap for
      the conversion of Gram-positive-only compounds into broad-spectrum antibiotics.

PMID- 29446463
TI  - Keeping eyes wide open: a commentary on Sibandze & Scafide (2017) 'Among nurses,
      how does education level impact professional values? A systematic review'.

PMID- 29446461
TI  - A method for red blood cell biotinylation in a closed system.
AB  - BACKGROUND: Several circumstances require the accurate measurement of red blood
      cell (RBC) survival and clearance, such as determination of posttransfusion
      recovery of stored RBCs to investigate the effect of new additive solutions. To
      this end, biotin as a marker of RBCs to track donor RBCs in the blood of the
      recipient has been used in many studies. However, so far only experimental,
      nonvalidated, biotin-labeled red cell concentrates (RCCs) are transfused. The
      goal of this study was to produce a standardized biotin-labeled RCC product in a
      fast, simple, and sterile manner that can be used for clinical research and for
      the evaluation of new blood products according to Good Practice Guidelines (GPG)
      for blood establishments. STUDY DESIGN AND METHODS: RCC fractions were labeled
      with two different concentrations of biotinylation reagent in a closed system, to
      prevent bacterial contamination of the end product. Using flow cytometry, the
      reproducibility and robustness of the biotin labeling was assessed, as well as
      the stability of the biotin label on the (un-)irradiated RCC fraction.
      Additionally, parameters such as phosphatidylserine (PS) exposure, sodium (Na),
      potassium (K), free hemoglobin, adenosine triphosphate (ATP), pH, and morphology
      were determined prior to and after biotin labeling to rule out detrimental
      effects of the labeling procedure on the RCC. RESULTS: Our data show that RCCs
      can be labeled under sterile conditions in a closed system with two different
      biotinylation reagent concentrations, without affecting the biological activity.
      CONCLUSION: An easy, rapid (<2 hr), and robust method was developed to
      manufacture biotin-labeled RCCs for clinical research compliant to GPG.

PMID- 29446464
TI  - Nurse advocacy and protection of older people.

PMID- 29446465
TI  - The importance of ICN Workforce Forums and the development of our profession.

PMID- 29446467
TI  - Morphological integration in the gorilla, chimpanzee, and human neck.
AB  - OBJECTIVES: Although integration studies are important to understand the
      evolution of organisms' traits across phylogenies, vertebral integration in
      primates is still largely unexplored. Here we describe and quantify patterns of
      morphological integration and modularity in the subaxial cervical vertebrae (C3
      C7) in extant hominines incorporating the potential influence of size. MATERIALS
      AND METHODS: Three-dimensional landmarks were digitized on 546 subaxial cervical
      vertebrae from 141 adult individuals of Gorilla gorilla, Pan troglodytes, and
      Homo sapiens. Integration and modularity, and the influence of size effects, were
      quantified using geometric morphometric approaches. RESULTS: All subaxial
      cervical vertebrae from the three species show a strong degree of integration.
      Gorillas show the highest degree of integration; conversely, humans have the
      lowest degree of integration. Analyses of allometric regression residuals show
      that size is an important factor promoting integration in gorillas, with lesser
      influence in chimpanzees and almost no effect in humans. DISCUSSION: Results
      point to a likely ancestral pattern of integration in non-human hominines,
      whereby the degree of integration decreases from cranial to caudal positions.
      Humans deviate from this pattern in the cranialmost (C3) and, to a lesser extent,
      in the caudalmost (C7) vertebrae, which are less integrated. These differences
      can be tentatively related to the emergence of bipedalism due to the presence of
      modern human-like C3 in australopiths, which still preserve a more chimpanzee
      like C7.

PMID- 29446468
TI  - Prevalence of occult hepatitis B in a population from the Brazilian Amazon
      region.
AB  - In the present study, we evaluated the prevalence of occult hepatitis B (OBI) in
      a population from the Brazilian Amazon region, identify circulating genotypes,
      and mutations in the S gene. One hundred eighty-one patients with negative
      serology for HBsAg and anti-HBs and positive serology for anti-HBc participated
      in the study. Detection of viral DNA, genotyping by sequencing, and analysis of
      nucleotide sequences to detect possible mutations were performed. HBV DNA was
      detected in 14.36% of the patients. Genotyping revealed genotype A in 88.46% of
      HBV DNA-positive subjects, with subgenotype A1 being the most prevalent (78.26%)
      followed by subgenotype A2 (21.74%). Genotype F was detected in 11.54% (all of
      them subgenotype F2). Amino acid substitutions were observed in the amplified S
      gene in individuals with OBI compared to HBsAg-positive individuals (evident
      infection). In conclusion, the results show a high prevalence of OBI in the
      population studied, with a pattern of genotypes A and F that circulate in the
      Brazilian Amazon region. Amino acid substitutions were detected in part of the S
      gene in patients with OBI. Further studies on the molecular epidemiology of HBV
      in this region are important to identify patients considered healthy but who are
      potential transmitters of the disease.

PMID- 29446469
TI  - Clinical trials in allergen immunotherapy: current concepts and future needs.
AB  - Allergen immunotherapy (AIT) is a safe, effective treatment for allergic
      rhinoconjunctivitis and allergic asthma. However, AIT's clinical effect is still
      contested-primarily due to heterogeneity in clinical trial designs, study
      populations, therapeutic formulations, and efficacy criteria. After discussing
      current concepts and unmet needs, an international panel of experts made several
      recommendations: (i) explore and validate definitions for (clinical) responders
      in AIT trials; (ii) use of well-documented, standardized provocation tests prior
      to inclusion of subjects with relevant diseases in AIT trials; (iii) monitoring
      neo-sensitizations and occurrence of new allergy in extended AIT trials, and
      exclusion of polyallergic participants; (iv) validation of allergen exposure
      chambers with regard to natural exposure; (v) in studies of seasonal allergies,
      focus on peak exposure but also consider organizing two parallel, geographically
      distinct but otherwise identical trials; (vi) discuss adaptive trial designs with
      the regulatory authorities; (vii) use e-health and m-health technologies to
      capture more information on individual exposure to allergens; (viii) initiate
      research on potential psychological, biochemical, immune, neural, and even
      genomic markers of the placebo response; (ix) identify trial designs and primary
      endpoints that will give children with allergies easier, faster access to AIT
      formulations; and (x) promote and apply standardized methods for reporting
      systemic and local adverse events. The latest technologies and trial designs may
      provide novel, ethical ways of reducing bias and heterogeneity in AIT clinical
      trials. There is scope for physicians, patient organizations, companies, and
      regulators to improve clinical trials in AIT and, ultimately, to provide patients
      with better treatments.

PMID- 29446470
TI  - HEV and HAV seroprevalence in men that have sex with men (MSM): An update from
      Milan, Italy.
AB  - Hepatitis E virus (HEV) is a feco-orally transmitted pathogen and one of the most
      common cause of acute hepatitis worldwide. Recent studies in developed countries
      suggested that a direct human-to-human contact such as for sexually transmitted
      diseases may play a significant role in the HEV spread. The aim of this study was
      to investigate the seroprevalence of HEV and HAV in a group of MSM, including
      subjects HIV, and Treponema infected, in Milan, Italy. The overall anti HEV IgG
      seroprevalence in MSM was 10.2% (65/636), instead in the control group the
      detection rate was 5.2% (15/288) (P < 0.05); the anti HAV seroprevalence was
      42.8% in MSM, when in the control group the positivity rate was 29.2% (P < 0.05).
      The rate of coinfection HEV/HAV was 14.6% in MSM and 1% in control group (P <
      0.05). In the future, sexual history, HIV status, and STI risk might address
      specific investigations to prevent spread of pathogens such HEV in MSM, before
      becoming a substantial public health problem like for HAV outbreaks.

PMID- 29446471
TI  - Randomised clinical trial of patient satisfaction with traditional and simplified
      complete dentures.
AB  - To clinically evaluate the patient satisfaction and associated costs of dentures
      made using a simplified procedure that eliminates assembly on the articulator and
      dentures made with the conventional technique. Single-blind randomised clinical
      trial. Forty edentulous patients were randomly divided into 2 groups. One group
      received dentures made using the conventional method (CG), and the other using a
      simplified technique (SG) that omits the use of functional impressions (with
      modelling compound and ZOE impression paste) and an articulator to assemble the
      models. Overall patient satisfaction was assessed at 3 and 6 months by means of a
      Numerical Rating Scale (NRS). The comparisons were made using a repeated measures
      ANOVA (P = .05). No significant differences were found in terms of the
      satisfaction stated by the patients or the quality of the prosthesis evaluated by
      a professional among the dentures made using the traditional (n = 17) and
      simplified (n = 21) techniques. The rehabilitation of an edentulous patient with
      a simplified technique for the preparation of a total prosthesis is a feasible,
      more economical alternative and accepted by most patients.

PMID- 29446472
TI  - Hantavirus induced cardiopulmonary syndrome: A public health concern.
AB  - Hantavirus cardiopulmonary syndrome is characterized by pulmonary capillary
      leakage and alveolar flooding, resulting in 50% mortality due to fulminant
      hypoxic respiratory failure. In addition, depression of cardiac function ensues,
      which complicates the picture with cardiogenic shock. Early diagnosis and
      appropriate use of extracorporeal membrane oxygenation (ECMO) are amongst the
      lifesaving interventions in this fatal illness. However, a recent case report
      demonstrates that implementation of high volume continuous hemofilteration along
      with protective ventilation reverses the cardiogenic shock within few hours in
      hantavirus infected patients. This review article is focused on the recent
      advances in clinical features, diagnosis, management, epidemiology, and
      pathogenesis of hantavirus induced cardiopulmonary syndrome. It provides
      information for clinicians to help in correct diagnosis during the early stages
      of viral infection that could improve the prognosis of this viral illness.

PMID- 29446473
TI  - A case of Kaposi varicelliform eruption progressing to herpes simplex virus
      hepatitis in an immunocompetent patient.

PMID- 29446474
TI  - Between hope and hopelessness: COPD patients' and their family members'
      experiences of interacting with healthcare providers - a qualitative longitudinal
      study.
AB  - BACKGROUND: Patient-family-healthcare provider interaction seems important for
      patients with chronic obstructive pulmonary disease (COPD) and their family
      members' self-management practices. Because the need for support might be
      enhanced after a hospitalisation, it might be beneficial to explore this
      interaction further in follow-up health care. AIM: To explore the meaning of
      patients' and their family members' experiences of interacting with healthcare
      providers to their daily self-management over time. METHODS: Participant
      observations and in-depth interviews were conducted repeatedly with 10 patients
      and seven family members during follow-up visits at hospital and at the
      participants' homes between 2014 and 2016. A phenomenological-hermeneutical
      approach was used to interpret the data. RESULTS: 'Between hope and hopelessness'
      involved frustrations, concerns and doubts, all of which could relate to the
      interaction with healthcare providers. 'Seeking support from healthcare
      services', 'navigating between healthcare providers' and 'collaborating with
      healthcare providers at home' could entail opportunities to strengthen self
      management and hope; however, it could also entail reduced faith in getting the
      right help and hopelessness. CONCLUSION: During a period of transition after
      hospitalisation, available and well-coordinated healthcare services, and
      alliances with healthcare professionals are crucial to COPD patients and their
      family members in terms of their self-management, hope and well-being.

PMID- 29446475
TI  - An audit of compliance with tuberculosis screening prior to treatment with
      biologics in psoriasis.

PMID- 29446476
TI  - The role of human papillomavirus in laryngeal cancer in Southern China.
AB  - To delineate the role of human papillomavirus (HPV) in laryngeal cancer in
      Southern Chinese, a retrospective cross-sectional study was conducted in a major
      otorhinolaryngology referral center in Hong Kong. Eighty-five Chinese patients
      with histology-confirmed laryngeal squamous cell carcinoma (LSCC) diagnosed
      between 2005 and 2010 were examined for the status of HPV by PCR, and the
      expression of p16 and p53 by immunohistochemistry. The HPV, p16 and p53 findings
      were correlated with clinicopathological features, recurrence and 5-year
      survival. HPV DNA was detected in one patient (1.2%, 95%CI: 0.2-6.4%) who had
      glottic cancer and harbored HPV-6. Overexpression of p16 and p53 were detected in
      11 (12.9%) and 47 (55.3%) cases, respectively. Recurrence occurred in 22.4% of
      patients at a median of 13 months. The 5-year overall survival and disease
      specific survival were 55.7% and 72.4%, respectively. Overexpression of p16 or
      p53 was not associated with clinicopathological features, recurrence or overall
      survival. HPV plays a limited role in laryngeal cancer in Hong Kong Southern
      Chinese. In contrast to oropharyngeal cancer, p16 cannot be used as a surrogate
      marker for oncogenic involvement of HPV and cannot predict survival in laryngeal
      cancer.

PMID- 29446478
TI  - Touch.

PMID- 29446477
TI  - ATP sensitive K+ channel subunits (Kir6.1, Kir6.2) are the candidate mediators
      regulating ameliorating effects of pulsed magnetic field on aortic contractility
      in diabetic rats.
AB  - Diabetes mellitus is a metabolic disease that causes increased morbidity and
      mortality in developed and developing countries. With recent advancements in
      technology, alternative treatment methods have begun to be investigated in the
      world. This study aims to evaluate the effect of pulsed magnetic field (PMF) on
      vascular complications and contractile activities of aortic rings along with
      Kir6.1 and Kir6.2 subunit expressions of ATP-sensitive potassium channels (KATP )
      in aortas of controlled-diabetic and non-controlled diabetic rats. Controlled
      diabetic and non-controlled diabetic adult male Wistar rats were exposed to PMF
      for a period of 6 weeks according to the PMF application protocol (1 h/day;
      intensity: 1.5 mT; consecutive frequency: 1, 10, 20, and 40 Hz). After PMF
      exposure, body weight and blood glucose levels were measured. Then, thoracic
      aorta tissue was extracted for relaxation-contraction and Kir6.1 and Kir6.2
      expression experiments. Blood plasma glucose levels, body weight, and aortic ring
      contraction percentage decreased in controlled-diabetic rats but increased in non
      controlled diabetic rats. PMF therapy repressed Kir6.1 mRNA expression in non
      controlled diabetic rats but not in controlled diabetic rats. Conversely, Kir6.2
      mRNA expressions were repressed both in controlled diabetic and non-controlled
      diabetic rats by PMF. Our findings suggest that the positive therapeutic effects
      of PMF may act through (KATP ) subunits and may frequently occur in insulin-free
      conditions. Bioelectromagnetics. 39:299-311, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29446479
TI  - A quantitative evaluation with an innovative wireless bio-impedance device to
      check improvement of limb lymphedema after receiving two-site vascularized lymph
      node transfer simultaneously in a patient.

PMID- 29446480
TI  - The correlation of TNF alpha levels with the lipid profile of dengue patients.
AB  - Immunological factors, such as cytokines, have been proposed as a cause of
      changes in the lipid profile of dengue patients. We studied whether serum lipid
      levels and serum TNF-alpha levels are associated in a group of dengue patients
      from an endemic region in the Northwest of Mexico. We found statistically
      important differences in the serum lipid profile and the TNF-alpha levels of
      dengue patients compared with the control group, were observed. However, TNF
      alpha levels did not correlate with the lipid profile of dengue patients.

PMID- 29446481
TI  - Clinical parameters of ovarian hyperstimulation syndrome following different
      hormonal triggers of oocyte maturation in IVF treatment.
AB  - OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic
      condition, predominantly related to the hormone used to induce oocyte maturation
      during IVF treatment. Kisspeptin is a hypothalamic neuropeptide that has recently
      been demonstrated to safely trigger final oocyte maturation during IVF treatment
      even in women at high risk of OHSS. However, to date, the safety of kisspeptin
      has not been compared to current hormonal triggers of oocyte maturation. DESIGN:
      We conducted a retrospective single-centre cohort study investigating symptoms
      and clinical parameters of early OHSS in women at high risk of OHSS (antral
      follicle count or total number of follicles on day of trigger >=23) triggered
      with human chorionic gonadotrophin (hCG) (n = 40), GnRH agonist (GnRHa; n = 99)
      or kisspeptin (n = 122) at Hammersmith Hospital IVF unit, London, UK (2013-2016).
      RESULTS: Clinical Parameters of OHSS: Median ovarian volume was larger following
      hCG (138 ml) than GnRHa (73 ml; P < .0001), and in turn kisspeptin (44 ml; P <
      .0001). Median ovarian volume remained enlarged 20-fold following hCG, 8-fold
      following GnRHa and 5-fold following kisspeptin compared to prestimulation
      ovarian volumes. Mean (+/-SD) ascitic volumes were lesser following GnRHa (9 +/-
      44 ml) and kisspeptin (5 +/- 8 ml) than hCG (62 +/- 84 ml; P < .0001). Symptoms
      of OHSS were most frequent following hCG and least frequent following kisspeptin.
      Diagnosis of OHSS: The odds ratio for OHSS diagnosis was 33.6 (CI 12.6-89.5)
      following hCG and 3.6 (CI 1.8-7.1) following GnRHa, when compared to kisspeptin.
      CONCLUSION: Triggering oocyte maturation by inducing endogenous gonadotrophin
      release is preferable to the use of exogenous hCG in women at high risk of OHSS.

PMID- 29446482
TI  - Oncogenesis as a Selective Force: Adaptive Evolution in the Face of a
      Transmissible Cancer.
AB  - Similar to parasites, malignant cells exploit the host for energy, resources and
      protection, thereby impairing host health and fitness. Although cancer is
      widespread in the animal kingdom, its impact on life history traits and
      strategies have rarely been documented. Devil facial tumour disease (DFTD), a
      transmissible cancer, afflicting Tasmanian devils (Sarcophilus harrisii),
      provides an ideal model system to monitor the impact of cancer on host life
      history, and to elucidate the evolutionary arms-race between malignant cells and
      their hosts. Here we provide an overview of parasite-induced host life history
      (LH) adaptations, then both phenotypic plasticity of LH responses and changes in
      allele frequencies that affect LH traits of Tasmanian devils in response to DFTD
      are discussed. We conclude that akin to parasites, cancer can directly and
      indirectly affect devil LH traits and trigger host evolutionary responses.
      Consequently, it is important to consider oncogenic processes as a selective
      force in wildlife.

PMID- 29446483
TI  - Adenovirus types associated with severe respiratory diseases: A retrospective 4
      year study in Kuwait.
AB  - Human adenovirus (HAdV) infection can result in a severe respiratory disease. The
      aim of this study was to identify HAdV types detected in patients hospitalized
      for severe respiratory illness. The study population consisted of 743 patients
      with severe respiratory disease admitted to four major hospitals in Kuwait
      between January 2013 and December 2016. Respiratory specimens were
      retrospectively screened for 20 respiratory viruses by real-time PCR. The HAdV
      hexon gene was amplified and directly sequenced, and HAdV types were identified
      by performing Bayesian phylogenetic analysis. HAdV DNA was detected in 27 (3.6%)
      patients, with peaks in November and March. Most patients were infants and young
      children suffering from pneumonia or acute bronchiolitis. The detected HAdV types
      were C1, C2, C5, B3, and B7. Clusters of HAdV C1, C2, and C5 were observed with
      high posterior probability. All patients infected with HAdV C5 and 50% of
      patients infected with HAdV C2 or B7 were admitted to the intensive care unit
      (ICU). Co-infection with other viruses was detected in 44.4% of patients. The
      most common co-infecting virus was rhinovirus (HRV). HAdV/HRV co-infection was
      detected in two children who presumably developed disseminated HAdV infection and
      died. This is the first report describing the circulation of HAdV types
      associated with severe outcomes in Kuwait. These findings highlight the need for
      a national surveillance system to monitor changes in predominant HAdV types and
      increased numbers of severe respiratory infections.

PMID- 29446484
TI  - Head position affects the direction of occlusal force during tapping movement.
AB  - Despite numerous reports describing the relationship between head position and
      mandibular movement in human subjects, the direction and magnitude of force at
      the occlusal contacts have not been investigated in relation to head position.
      The objective was to investigate the effect of head position on the direction of
      occlusal force while subjects performed a tapping movement. Twenty-three healthy
      adult subjects were asked to sit on a chair with their back upright and to
      perform 15 tapping movements in five different head positions: natural head
      position (control); forward; backward; and right and left rolled. The direction
      and magnitude of force were measured using a small triaxial force sensor. The
      Wilcoxon signed-rank test and Bonferroni test were used to compare head positions
      in each angle of the anteroposterior axis direction and the lateral axis
      direction with respect to the superior axis. The force element in the
      anteroposterior axis shifted to the forward direction in the head position
      pitched backward, compared with control, pitched forward and rolled left
      positions (P = .02, <.01 and <.01, respectively). The force direction in the
      lateral axis with the head position rolled to the right or left shifted to the
      left and right directions, respectively, compared with those in the other
      positions (P < .05). Results of this study suggest that the head should be
      maintained in a position in which a stable tapping movement can be performed in a
      relaxed position without anteroposterior and lateral loading.

PMID- 29446485
TI  - Effects of glucosamine supplements on painful temporomandibular joint
      osteoarthritis: A systematic review.
AB  - The purpose of this study was to systematically review the literature for studies
      that assessed the effects of glucosamine supplements (GS) on pain and maximum
      mouth opening (MMO) restriction compared to other therapies, placebo or no
      intervention on painful temporomandibular joint osteoarthritis (TMJ OA).
      Randomised controlled trials were selected in a two-phase process. Seven
      electronic databases, in addition to three grey literature databases, were
      searched. Risk of bias was assessed using the Cochrane Collaboration's tool for
      assessing risk of bias in randomised trials. Twelve potentially eligible studies
      were identified, from which three were finally included. Furthermore, two were
      categorised at low risk and one at high risk of bias. Intervention groups were
      treated with glucosamine-sulphate, while controls were treated with placebo or
      ibuprofen. In two studies, GS were equally effective regarding pain reduction and
      mouth opening improvement compared to ibuprofen taken two or three times a day
      over 12 weeks; however, one study did not find significant differences in follow
      up evaluations concerning these clinical variables in both glucosamine and
      placebo groups administered over six weeks. There is very low evidence regarding
      GS therapeutic effects on TMJ OA. Considering a follow-up of 12 weeks, GS were as
      effective as ibuprofen taken two or three times a day. However, over six weeks of
      medication intake, GS were not superior to placebo. Still, included studies
      presented major drawbacks, and therefore, conclusions must be interpreted with
      caution.

PMID- 29446487
TI  - TM2D3 rs675436 or FGFR2 rs755793 polymorphisms and susceptibility to Epstein-Barr
      virus-associated tumors in Chinese Han population.
AB  - Epstein-Barr virus (EBV) is etiologically linked to nasopharyngeal carcinoma,
      lymphoma, and gastric carcinoma. The aim of this study was to assess the
      association of TM2 domain containing 3 (TM2D3) and fibroblast growth factor
      receptor 2 (FGFR2) SNPs rs675436 and rs755793 with susceptibility to EBV
      associated tumors in Chinese Han population. Genomic DNA of 415 patients with
      cancer and 99 healthy controls was assessed using a MALDI-TOF mass spectrometer,
      and was genotyped in EBV-associated/-negative gastric cancer (EBVa/nGC), EBV
      associated/-negative nasopharyngeal carcinoma (EBVa/nNPC), EBV-associated/
      negative lymphoma (EBVa/nL), and normal controls (NC). The chi-squared (chi2 )
      test or Fisher's exact test was used to compare all results and P < 0.05 was
      considered statistically significant. The results showed that the G-allele of
      rs675436 was less prevalent in EBVaGC as than in the other groups, while the T
      allele was more prevalent in EBVaGC (EBVaGC vs EBVnGC: P = 0.005, OR = 10.522,
      95%CI = 1.377-80.376; EBVaGC vs NC: P = 0.005, OR = 10.637, 95%CI = 1.392
      81.263). Interestingly, the distribution of the genotype and allele frequencies
      of rs675436 was significantly different between EBVaGC and EBVaNPC. Neither the
      genotype nor allele frequency of rs755793 was statistically different between any
      two groups (P > 0.05). These findings indicated that the TT genotype and T allele
      frequencies of rs675436 were associated with an increased risk of EBVaGC, while
      allele A or G of rs755793 had no effect on the occurrence of EBV-associated
      tumors in Chinese Han population.

PMID- 29446486
TI  - Interleukin-17A participates in podocyte injury by inducing IL-1beta secretion
      through ROS-NLRP3 inflammasome-caspase-1 pathway.
AB  - Studies show that the Th17/IL-17A axis plays an important role in the
      pathogenesis of kidney diseases. Previously, we also showed that IL-17A may play
      a role in the pathogenesis of primary nephrotic syndrome; however, the underlying
      mechanism(s) is unclear. The aim of this study was to explore the molecular
      mechanism of IL-17A-inducing podocyte injury in vitro. In this study, the NLRP3
      inflammasome activation and the morphology of podocytes were detected by Western
      blot and immunofluorescence. The results showed that podocytes persistently
      expressed IL-17A receptor and that NLRP3 inflammasome in these cells was
      activated upon exposure to IL-17A. Also, activity of caspase-1 and secretion of
      IL-1beta increased in the presence of IL-17A. In addition, IL-17A disrupted
      podocyte morphology by decreasing expression of podocin and increasing expression
      of desmin. Blockade of intracellular ROS or inhibition of caspase-1 prevented
      activation of the NLRP3 inflammasome, thereby restoring podocyte morphology.
      Taken together, the results suggest that IL-17A induces podocyte injury by
      activating the NLRP3 inflammasome and IL-1beta secretion and contributes to
      disruption of the kidney's filtration system.

PMID- 29446488
TI  - Spatial trends in a biomagnifying contaminant: Application of amino acid compound
      specific stable nitrogen isotope analysis to the interpretation of bird mercury
      levels.
AB  - Levels of biomagnifying contaminants are greatest in high-trophic level biota
      (e.g., predatory birds such as gulls). Gull eggs have been used to assess
      contaminant spatial patterns and sources, but such assessments must consider how
      organism trophic position may influence spatial inferences. Stable nitrogen
      isotopes (delta15 N) in bulk tissue are routinely used in this context. However,
      bulk delta15 N values are only useful if spatial differences in baseline delta15
      N values are considered. Amino acid compound-specific stable nitrogen isotope
      analysis can generate estimates of baseline delta15 N values and trophic position
      from the same sample. In the present study, eggs (n = 428) of California (Larus
      californicus), herring (Larus argentatus smithsonianus), and ring-billed (Larus
      delawarensis) gulls were used to assess spatial patterns in mercury (Hg)
      availability in 12 western Canadian lakes located over 14 degrees of latitude,
      with amino acid compound-specific stable isotope analysis adjustment of egg Hg
      levels for trophic position. Mean trophic position-adjusted egg Hg levels
      (micrograms per gram, dry wt) were greatest at sites in receiving waters of the
      Athabasca River (X- = 0.70) compared to southern (X- = 0.39) and northern (X- =
      0.50) regions. Research is required to investigate factors (e.g., local Hg
      released as a result of human activities, processes influencing Hg methylation)
      which may be responsible for greater Hg availability in the lower Athabasca River
      basin. However, it is clear that amino acid compound-specific stable isotope
      analysis is a valuable tool for assessing contaminant spatial patterns. Environ
      Toxicol Chem 2018;37:1466-1475. (c) 2018 SETAC.

PMID- 29446489
TI  - Alcohol attenuates anti-HCV function of IFN-lambda1 through up-regulation of
      PLASy expression in human hepatic cells.
AB  - Alcohol could compromise the anti-hepatitis C virus (HCV) function of interferon
      alpha (IFN-alpha). However, little information is available about the effect of
      alcohol on interferon-lambda (IFN-lambda, type III IFN), a novel candidate for
      development of therapy for HCV infection. Huh7 cells were infected with HCV JFH-1
      virus, then treated with alcohol, and/or IFN-lambda1. RT-PCR and Western blot
      were used to detect the levels of HCV and key cellular factors. Overexpression or
      silencing expression was performed to verify the role of key factors in alcohol
      attenuated anti-HCV function of IFN-lambda1. Alcohol treatment compromised anti
      HCV effect of IFN-lambda1 in HCV JFH-1-infected Huh7 cells, evidenced by the
      significantly increased levels of HCV RNA, and HCV core protein in alcohol-/IFN
      lambda1-treated cells compared to cells with IFN-lambda1 treatment alone.
      Investigation of the mechanisms responsible for the alcohol action revealed that
      alcohol enhanced the expression of protein inhibitor of activated STAT (PIASy).
      Overexpression of PIASy compromised anti-HCV ability of IFN-lambda1, whereas
      silencing expression of PIASy partly restored the alcohol-attenuated anti-HCV
      effect of IFN-lambda1. More importantly, overexpression of PIASy significantly
      down-regulated the level of IFN-lambda1-indcued phosphorylation of STAT1 (p
      STAT1), an important adaptor in IFN-lambda pathway, as well as reduced the
      expression of IFN-lambda1-induced IFN-stimulated genes 56 (ISG56), and myxovirus
      resistance 1 (Mx1), two antiviral effectors in in IFN-lambda pathway. These
      findings indicate that alcohol, through inducing the expression of negative
      regulator in IFN-lambda pathway, inhibits IFN-lambda-mediated anti-HCV action in
      human hepatic cells, which may lead to the poor efficacy of IFN-lambda-based
      therapy against HCV infection.

PMID- 29446490
TI  - A 3-dimensional-printed patient-specific guide system for minimally invasive
      plate osteosynthesis of a comminuted mid-diaphyseal humeral fracture in a cat.
AB  - OBJECTIVE: To report the use of a 3-dimensional (3D)-printed patient-specific
      reduction guide system to facilitate minimally invasive plate osteosynthesis
      (MIPO) of a humeral fracture in a cat. STUDY DESIGN: Case report. ANIMALS: A 9
      year-old male neutered domestic short hair cat weighing 4.4 kg. METHODS: A 9-year
      old male domestic short hair cat was presented with a comminuted, mid-diaphyseal
      left humeral fracture. Computed tomographic data were processed to yield 3D mesh
      representations of both humeri and subsequently manipulated in computer-aided
      design software. The mirrored, intact humerus was used as a template for
      appropriate spatial orientation of the major proximal and distal fracture
      fragments. Patient-specific Ellis pin orientation guides and a reduction guide
      were designed and 3D printed. The guide system was used intraoperatively to align
      the major fracture fragments before application of locking internal fixation via
      standard MIPO surgical portals. RESULTS: Internal fixation of the fracture
      resulted in appropriate bone alignment. Recovery was uncomplicated, with early
      return to normal limb function and radiographic evidence of advanced fracture
      healing after 4 months. CONCLUSION: A 3D-printed patient-specific reduction guide
      system facilitated accurate alignment of a comminuted humeral fracture during
      MIPO without intraoperative imaging.

PMID- 29446491
TI  - Characterization of morphological conversion of Helicobacter pylori under
      anaerobic conditions.
AB  - Helicobacter pylori (H. pylori), a gram-negative microaerophilic bacterial
      pathogen that colonizes the stomachs of more than half of all humans, is linked
      to chronic gastritis, peptic ulcers and gastric cancer. Spiral-shaped H. pylori
      undergo morphologic conversion to a viable but not culturable coccoid form when
      they transit from the microaerobic stomach into the anaerobic intestinal tract.
      However, little is known about the morphological and pathogenic characteristics
      of H. pylori under prolonged anaerobic conditions. In this study, scanning
      electron microscopy was used to document anaerobiosis-induced morphological
      changes of H. pylori, from helical to coccoid to a newly defined fragmented form.
      Western blot analysis indicated that all three forms express certain pathogenic
      proteins, including the bacterial cytotoxin-associated gene A (CagA), components
      of the cag-Type IV secretion system (TFSS), the blood group antigen-binding
      adhesin BabA, and UreA (an apoenzyme of urease), almost equally. Similar urease
      activities were also detected in all three forms of H. pylori. However, in
      contrast to the helical form, bacterial motility and TFSS activity were found to
      have been abrogated in the anaerobiosis-induced coccoid and fragmented forms of
      H. pylori. Notably, it was demonstrated that some of the anaerobiosis-induced
      fragmented state cells could be converted to proliferation-competent helical
      bacteria in vitro. These results indicate that prolonged exposure to the
      anaerobic intestine may not eliminate the potential for H. pylori to revert to
      the helical pathogenic state.

PMID- 29446492
TI  - Bayesian reconstruction of the evolutionary history and cross-species transition
      of variola virus and orthopoxviruses.
AB  - Variola virus (VARV), the causative agent of smallpox, is an exclusively human
      virus belonging to the genus Orthopoxvirus, which includes many other viral
      species covering a wide range of mammal hosts, such as vaccinia, cowpox,
      camelpox, taterapox, ectromelia, and monkeypox virus. The tempo and mode of
      evolution of Orthopoxviruses were reconstructed using a Bayesian phylodynamic
      framework by analysing 80 hemagglutinin sequences retrieved from public
      databases. Bayesian phylogeography was used to estimate their putative ancestral
      hosts. In order to estimate the substitution rate, the tree including all of the
      available Orthopoxviruses was calibrated using historical references dating the
      South American variola minor clade (alastrim) to between the XVI and XIX century.
      The mean substitution rate determined by the analysis was 6.5 * 10-6
      substitutions/site/year. Based on this evolutionary estimate, the time of the
      most recent common ancestor of the genus Orthopoxvirus was placed at about 10 000
      years before the present. Cowpox virus was the species closest to the root of the
      phylogenetic tree. The root of VARV circulating in the XX century was estimated
      to be about 700 years ago, corresponding to about 1300 AD. The divergence between
      West African and South American VARV went back about 500 years ago (falling
      approximately in the XVI century). A rodent species is the most probable
      ancestral host from which the ancestors of all the known Orthopoxviruses were
      transmitted to the other mammal host species, and each of these species
      represented a dead-end for each new poxvirus species, without any further inter
      specific spread.

PMID- 29446493
TI  - Anti-donor antibody induction following intramuscular injections of allogeneic
      mesenchymal stromal cells.
AB  - Allogeneic mesenchymal stromal cells (allo-MSC) are a promising "off-the-shelf"
      therapy with anti-inflammatory and pro-repair properties. This study investigated
      humoral immune responses to intramuscular (IM) injections of allo-MSC. Total and
      isotype-specific anti-donor IgG and donor-specific complement-mediated lysis were
      determined in sera from healthy mice 2 weeks after single or repeated IM
      injections of fully mismatched-MHC allo-MSC with comparison to mice receiving
      syngeneic MSC, allogeneic splenocytes or saline. In mice subjected to hind limb
      ischemia (HLI), anti-donor IgG was analyzed following IM allo-MSC injection with
      and without administration of the T-cell immunosuppressant tacrolimus. Recipients
      of single and repeated IM allo-MSC developed readily-detectable anti-donor IgG.
      Serum anti-donor IgG levels were similar to those of allo-splenocyte recipients
      but had higher IgG1/IgG2a ratio and variable capacity for complement-mediated
      lysis of donor cells. The induced anti-donor IgG bound readily to allo-MSC and
      this binding was increased following allo-MSC pretreatment with interferon gamma.
      In mice with HLI, IM injection of allo-MSC into the ischemic limb was also
      associated with induction of anti-donor IgG but this was abrogated by tacrolimus
      (FK-506). The results indicate that allo-MSC are inherently immunogenic when
      delivered intramuscularly to healthy and ischemic mouse hind limb, but induce an
      IgG1-skewed humoral response that is suppressed by tacrolimus.

PMID- 29446494
TI  - Prepared for surgery - Communication in nurses' preoperative consultations with
      patients undergoing surgery for colorectal cancer after a person-centred
      intervention.
AB  - AIMS AND OBJECTIVES: To describe preoperative communication after a person
      centred intervention in nurses' consultations with patients undergoing surgery
      for colorectal cancer. BACKGROUND: Patients all over the world scheduled for
      surgery are referred to preoperative consultations with healthcare professionals.
      The goal is to assess the risk of perioperative complications, improving quality
      of care and enabling patients to be prepared for surgery and recovery. A person
      centred intervention was developed, which consisted of an interactive written
      patient education material and person-centred communication. DESIGN: An
      explorative quantitative and qualitative study based on 18 audio-taped
      transcriptions. METHODS: Eighteen patients preoperative nursing consultations at
      three Swedish hospitals were analysed quantitatively regarding structure: words,
      time, phases, questions, discursive space, and qualitatively: topics and how the
      person-centred communication appeared in the consultations. RESULTS: The median
      time for consultations was 27 min (range 13-64 min). The nurses used two-thirds
      of the discursive space in the consultations with the patients. The patient
      education material was used as a support to structure the consultation and
      discuss sensitive and difficult issues. Seven topics were discussed during the
      consultation. Two different approaches to communication were identified: Talking
      with the patient versus Talking to the patient. Talking with the patient (seen as
      person-centred communication) was defined as: listening to the narrative and
      confirming each other, raising difficult topics, seeing each other as persons,
      building on strengths and resources, preparing for surgery and asking open
      questions. CONCLUSION: Ways of communicating influence how the preoperative
      consultation develops. Talking with the patient could be seen as person-centred
      communication in the preoperative care, and when using this approach, the
      intervention purpose of person-centred communication was met. RELEVANCE TO
      CLINICAL PRACTICE: Education in person-centred communication is important for
      nurses to improve their skills in performing preoperative consultations.

PMID- 29446495
TI  - The role of COBRA-LIKE 2 function, as part of the complex network of interacting
      pathways regulating Arabidopsis seed mucilage polysaccharide matrix organization.
AB  - The production of hydrophilic mucilage along the course of seed coat epidermal
      cell differentiation is a common adaptation in angiosperms. Previous studies have
      identified COBRA-LIKE 2 (COBL2), a member of the COBRA-LIKE gene family, as a
      novel component required for crystalline cellulose deposition in seed coat
      epidermal cells. In recent years, Arabidopsis seed coat epidermal cells (SCEs),
      also called mucilage secretory cells, have emerged as a powerful model system for
      the study of plant cell wall components biosynthesis, secretion, assembly and de
      muro modification. Despite accumulating data, the molecular mechanism of COBL
      function remains largely unknown. In the current research, we utilized genetic
      interactions to study the role of COBL2 as part of the protein network required
      for seed mucilage production. Using correlative phenotyping of structural and
      biochemical characteristics, unique features of the cobl2 extruded mucilage are
      revealed, including: 'unraveled' ray morphology, loss of primary cell wall
      'pyramidal' organization, reduced Ruthenium red staining intensity of the
      adherent mucilage layer, and increased levels of the monosaccharides arabinose
      and galactose. Examination of the cobl2cesa5 double mutant provides insight into
      the interface between COBL function and cellulose deposition. Additionally,
      genetic interactions between cobl2 and fei1fei2 as well as between each of these
      mutants to mucilage-modified 2 (mum2) suggest that COBL2 functions independently
      of the FEI-SOS pathway. Altogether, the presented data place COBL2 within the
      complex protein network required for cell wall deposition in the context of seed
      mucilage and introduce new methodology expending the seed mucilage phenotyping
      toolbox.

PMID- 29446496
TI  - The voice of nurses: Novice nurses' first experiences in a clinical setting. A
      longitudinal diary study.
AB  - AIMS AND OBJECTIVES: To gain greater understanding of which personal and
      professional demands novice nurses are confronted with and what can be done to
      improve the transition from novice to professional staff nurse. BACKGROUND:
      Novice nurses are confronted with a lot of physical, emotional and intellectual
      changes in the role-transition process from student nurse to professional staff
      nurse, which are often related to feelings of confusion, uncertainty and stress.
      Few studies have investigated, on a longitudinal basis, the lived experiences of
      novice nurses in the clinical setting. DESIGN: The study adopted a qualitative
      longitudinal approach to investigate the described experiences of novice nurses
      during their first 2 years after graduation. Written diaries were selected for
      optimal data collection. METHODS: A sample of eighteen novice nurses was
      recruited from several wards at a University Medical Center in the Netherlands.
      The inclusion criteria were a Bachelor's degree in nursing, aged under 30, and no
      more than 1 year's work experience. Data were collected from weekly measurements
      from September 2013-September 2014. RESULTS: Eight major themes emerged from the
      diaries (n = 580): relatedness, competence, development, organisational context,
      existential events, goals, autonomy and fit. This study revealed that the need
      for relatedness was by far the most reported theme. Support and positive feedback
      from colleagues appeared to be crucial for novices starting work in a highly
      complex environment. CONCLUSION: This study showed that one of the strategies
      novice nurses use to deal with challenging and existential situations is to share
      their experiences with colleagues. Therefore, novice nurses should always work in
      a safe environment which enables this. RELEVANCE TO CLINICAL PRACTICE:
      Identification of key issues around understanding novice nurses' first clinical
      experiences may help to improve their transition from novice to professional
      staff nurse. The presence and support from supervisors and mentors are inevitable
      to keep novice nurses motivated for the profession.

PMID- 29446497
TI  - Specific Interaction Sites Determine Differential Adsorption of Protein
      Structural Isomers on Nanoparticle Surfaces.
AB  - In biological systems, nanoparticles (NPs) elicit bioactivity upon interaction
      with proteins. As a result of post-translational modification, proteins occur in
      a variety of alternative covalent forms, including structural isomers, which
      present unique molecular surfaces. We aimed at a detailed description of the
      recognition of protein isomeric species by NP surfaces. The transient adsorption
      of isomeric ubiquitin (Ub) dimers by NPs was investigated by solution NMR
      spectroscopy. Lys63- and Lys48-linked Ub2 were adsorbed by large anionic NPs with
      different affinities, whereas the binding strength was similar in the cases of
      smaller particles. After the incorporation of paramagnetic tags into NPs, the
      observed site-resolved paramagnetic footprints provided a high-resolution map of
      the different protein surfaces binding to NPs. The approach described could be
      extended to further protein isoforms and more specialized NP systems to allow
      better control of the interactions between NPs and protein targets.

PMID- 29446498
TI  - Simultaneous G-Quadruplex DNA Logic.
AB  - A fundamental principle of digital computer operation is Boolean logic, where
      inputs and outputs are described by binary integer voltages. Similarly, inputs
      and outputs may be processed on the molecular level as exemplified by synthetic
      circuits that exploit the programmability of DNA base-pairing. Unlike modern
      computers, which execute large numbers of logic gates in parallel, most
      implementations of molecular logic have been limited to single computing tasks,
      or sensing applications. This work reports three G-quadruplex-based logic gates
      that operate simultaneously in a single reaction vessel. The gates respond to
      unique Boolean DNA inputs by undergoing topological conversion from duplex to G
      quadruplex states that were resolved using a thioflavin T dye and gel
      electrophoresis. The modular, addressable, and label-free approach could be
      incorporated into DNA-based sensors, or used for resolving and debugging parallel
      processes in DNA computing applications.

PMID- 29446499
TI  - Magnetic Switching by the In Situ Electrochemical Control of Quasi-Spin-Peierls
      Singlet States in a Three-Dimensional Spin Lattice Incorporating TTF-TCNQ Salts.
AB  - Magnetic phase switching in a coordination polymer is reported, which is
      demonstrated by combining two processes: (A) the pre-organization of
      magnetic/redox-active molecules into a framework, and (B) a post-treatment
      through electrochemical tuning of the pre-organized molecules. A TTF.+ -TCNQ.-
      salt (TTF=tetrathiafulvalene; TCNQ=7,7,8,8-tetracyano-p-quinodimethane) was
      incorporated into a three-dimensional framework with paddlewheel-type dimetal(II,
      II) units ([M2II,II ]; M=Ru with S=1, 1; and Rh with S=0, 2), where the [M2II,II
      ] and TCNQ.- units form the coordinating framework, and TTF.+ is located in the
      pores of framework, forming an irregular pi-stacking alternating column with the
      TCNQ.- in the framework. In 1, the spins of [Ru2II,II ] and TCNQ.- units make a
      magnetic correlation through the framework upon decreasing the temperature from
      300 K, which is, however, suddenly suppressed below 137 K (=Td (1)) by the
      formation of a spin singlet in the TTF.+ -TCNQ.- columns, as seen in the spin
      Peierls transition (Td (2)=200 K). This material was incorporated as a cathode in
      a Li-ion battery (LIB); a long-range ferrimagnetic correlation was formed through
      the three-dimensional [{Ru2II,II }2 TCNQ]- framework at Tc =78 K in the discharge
      process. The reversible magnetic phase switching between the non-volatile
      ferrimagnetic and paramagnetic states, resulting from the local spin tuning of
      quasi-spin-Peierls singlet, is demonstrated through the discharge/charge cycling
      of the LIB.

PMID- 29446500
TI  - Building the foundation to generate a fundamental care standardised data set.
AB  - AIM AND OBJECTIVES: This paper provides an overview of the current state of
      performance measurement, key trends and a methodological approach to leverage in
      efforts to generate a standardised data set for fundamental care. BACKGROUND:
      Considerable transformation is occurring in health care globally with
      organisations focusing on achieving the quadruple aim of improving the experience
      of care, the health of populations, and the experience of providing care while
      reducing per capita costs of health care. In response, healthcare organisations
      are employing performance measurement and quality improvement methods to achieve
      the quadruple aim. Despite the plethora of measures available to health managers,
      there is no standardised data set and virtually no indicators reflecting how
      patients actually experience the delivery of fundamental care, such as nutrition,
      hydration, mobility, respect, education and psychosocial support. CONCLUSIONS:
      Given the linkages of fundamental care to safety and quality metrics, efforts to
      build the evidence base and knowledge that captures the impact of enacting
      fundamental care across the healthcare continuum and lifespan should include
      generating a routinely collected data set of relevant measures. RELEVANCE TO
      CLINICAL PRACTICE: This paper provides an overview of the current state of
      performance measurement, key trends and a methodological approach to leverage in
      efforts to generate a standardised data set for fundamental care. Standardised
      data sets enable comparability of data across clinical populations, healthcare
      sectors, geographic locations and time and provide data about care to support
      clinical, administrative and health policy decision-making.

PMID- 29446501
TI  - alpha-Hydroxy Ketones as Masked Ester Donors in Bronsted Base Catalyzed Conjugate
      Additions to Nitroalkenes.
AB  - The catalyst-controlled enantioselective direct addition reaction of enolizable
      esters and related carboxylic acid derivatives to pi electrophiles remains a
      difficult synthetic transformation. In this study, the suitability of alpha
      hydroxy ketones as ester equivalents capable of being activated by bifunctional
      Bronsted base catalysts in the context of conjugate addition reactions to
      nitroolefins is demonstrated. The scope of the reaction, which affords the
      corresponding Michael adducts with very high stereoselectivity (diastereomeric
      ratio (d.r.) >=95:5, up to 99 % enantiomeric excess (ee)), and its limitations
      are explored, as is the aftermath elaboration of adducts into densely
      functionalized enantioenriched products.

PMID- 29446502
TI  - Alcohol, pattern of drinking and all-cause mortality in Russia, Belarus and
      Hungary: a retrospective indirect cohort study based on mortality of relatives.
AB  - AIMS: To assess the relationship between alcohol intake frequency and mortality
      among males and females in three Eastern European populations, and to estimate
      the additional mortality risk posed by a combination of frequent drinking, binge
      drinking and other hazardous drinking habits. DESIGN: Retrospective cohort study;
      the cohort consisted of close relatives of survey participants. SETTING: Middle
      sized settlements in Russia, Belarus and Hungary. PARTICIPANTS: A total of 124
      150 subjects aged 35-69 years in 1998 and followed-up until 2013. MEASUREMENTS:
      Survey respondents provided information on their mothers, fathers, siblings and
      partners of female respondents. This information, including current vital status
      and dates of birth and death, was used to construct the cohort of relatives.
      Alcohol consumption indices, reported by survey participants, included drinking
      frequency, binge drinking and hazardous drinking [consuming non-beverage and/or
      illicitly-produced alcohol and/or heavy drinking over several days (zapoi in
      Russian)]. FINDINGS: Drinking frequency was associated positively with mortality
      in all three countries and both genders. At each drinking frequency level,
      mortality risk increased among those who also engaged in binge and/or hazardous
      drinking. Regular male drinkers who were also binge drinkers and hazardous
      drinkers had the highest risk of death; their hazard ratios (HR), compared with
      non-binge-non-hazardous occasional drinkers, were 2.56 [95% confidence interval
      (CI) = 2.27-2.88], 2.14 (95% CI = 1.84-2.48) and 2.11 (95% CI = 1.90-2.35) in
      Russia, Belarus and Hungary, respectively. In women, the corresponding HRs (using
      a lower frequency cut-off) were 2.86 (95% CI = 1.99-4.12) in Russia, 3.44 (95% CI
      = 2.17-5.44) in Belarus and 3.01 (95% CI = 2.26-4.01) in Hungary. CONCLUSIONS:
      Drinking frequency is associated positively with mortality among men and women in
      Russia, Belarus and Hungary. The mortality risk is higher among frequent drinkers
      who exhibit binge and hazardous drinking patterns.

PMID- 29446503
TI  - CRISPR/Cas9-mediated mutagenesis of lncRNA1459 alters tomato fruit ripening.
AB  - With the development of high-throughput sequencing, many long non-coding RNAs
      (lncRNAs) have been found to play important roles in diverse biological
      processes. However, the biological functions of most plant lncRNAs are still
      unknown. We have previously discovered a tomato ripening-related lncRNA,
      lncRNA1459. Here, we cloned the full-length lncRNA1459, giving two transcript
      isoforms. In addition, lncRNA1459 exhibited a specific location in the nucleus.
      Furthermore, in order to fully identify the function of lncRNA1459 in tomato
      ripening, loss-of-function mutants of lncRNA1459 were developed using clustered
      regularly interspaced short palindromic repeats (CRISPR)/-associated protein 9
      (Cas9)-induced genome editing technology. Compared with wild-type fruits, the
      tomato ripening process was significantly repressed in lncRNA1459 mutants.
      Ethylene production and lycopene accumulation were largely repressed in
      lncRNA1459 mutants. Additionally, genes related to ethylene and carotenoid
      biosynthesis were distinctly downregulated in lncRNA1459 mutants compared with
      wild-type fruits. Moreover, expression of numerous ripening-related genes was
      changed significantly when lncRNA1459 was knocked out. Expression of potential
      tomato ripening-related lncRNAs was also specifically changed after knocking out
      lncRNA1459. Taken together, these results provide insight into the role of
      lncRNA1459 in tomato fruit ripening.

PMID- 29446504
TI  - Mechanism of Enolate Transfer between Si and Cu.
AB  - Exchange of X (F, Cl, OMe) and a substituted enolate chain between SiMe3 and
      various CuI complexes was examined. Reaction mechanisms pass through a cyclic
      transition state in which the reaction coordinate is associated with rotation of
      the SiMe3 moiety. The dependence of the thermodynamic and kinetic features on the
      nature of the active and ancillary ligands was examined. Formation of copper
      enolate is shown to be favored when stabilized enolates are used. Replacement of
      F by Cl reverses the preference of the reaction. This is associated with the
      small difference between the Cu-Cl and Si-Cl bond energies, in contrast to other
      Si-X bonds, which are systematically stronger than their Cu-X analogues.

PMID- 29446506
TI  - Picomolar-scale compound-specific isotope analyses.
AB  - RATIONALE: We report modifications to compound-specific isotope analyses (CSIA)
      to enable high-precision isotopic analyses of picomoles of carbon for intact
      organic molecules. This sample size is two orders of magnitude below the amounts
      required for commercial systems. The greatly enhanced sensitivity of this system
      expands molecular isotope studies and applications previously prohibited by low
      concentrations and small samples. METHODS: We utilize the resolving power and low
      volumetric flow rates of narrow-bore capillary gas chromatography to improve
      sample transfer efficiency while maintaining narrow peak widths. Post-column peak
      broadening is minimized using a micro-fluidic valve for solvent diversion,
      capillary combustion reactor, narrow-bore capillary transfer lines, and cryogenic
      water trap. The mass spectrometer was fitted with collector amplifiers configured
      to 25 ms response times and a data logger board with firmware capable of rapid
      data acquisition. Carbon dioxide gas was introduced directly into the ion source
      to evaluate the dynamic range of the system and accuracy and precision of carbon
      isotope ratio (delta13 C value) measurements. The accuracy and precision for
      combusted compounds were evaluated using a suite of n-alkanes. RESULTS: For >=30
      pmol carbon introduced directly into the ion source, the mean difference between
      the measured and expected delta13 C values is 0.030/00 (1sigma, n = 57) and the
      standard deviation of replicate measurements is 0.110/00 (1sigma). The CO2 peak
      widths generated by the exponential dilution flask were 250 ms and the peak
      widths produced by combusting n-alkanes were ca 500 ms, less than 25% the width
      of conventional gas chromatography peaks. For a mixture of 15 n-alkanes (n-C16 to
      n-C30 ), the accuracy is 0.30/00 (1sigma) and precision is 0.90/00 (1sigma) for
      replicate delta13 C measurements with 100 pmol carbon per compound on column.
      CONCLUSIONS: The pico-CSIA method described here offers improved chromatographic
      resolution and reduces sample size requirements by two orders of magnitude. These
      advances significantly broaden the available analytical window for CSIA in
      research areas frequently hindered by sample size limitations, such as forensics,
      paleoclimate, astrobiology, and biochemistry.

PMID- 29446505
TI  - ClpC and MecA, components of a proteolytic machine, prevent Spo0A-P-dependent
      transcription without degradation.
AB  - In Bacillus subtilis, a proteolytic machine composed of MecA, ClpC and ClpP
      degrades the transcription factor ComK, controlling its accumulation during
      growth. MecA also inhibits sporulation and biofilm formation by down-regulating
      spoIIG and sinI, genes that are dependent for their transcription on the
      phosphorylated protein Spo0A-P. Additionally, MecA has been shown to interact in
      vitro with Spo0A. Although the inhibitory effect on transcription requires MecA's
      binding partner ClpC, inhibition is not accompanied by the degradation of Spo0A,
      pointing to a previously unsuspected regulatory mechanism involving these
      proteins. Here, we further investigate the MecA and ClpC effects on Spo0A-P
      dependent transcription. We show that MecA inhibits the transcription of several
      Spo0A-P activated genes, but fails to de-repress several Spo0A-P repressed
      promoters. This demonstrates that MecA and ClpC do not act by preventing the
      binding of Spo0A-P to its target promoters. Consistent with this, MecA by itself
      has no effect in vitro on the transcription from PspoIIG while the addition of
      both MecA and ClpC has a strong inhibitory effect. A complex of MecA and ClpC
      likely binds to Spo0A-P on its target promoters, preventing the activation of
      transcription. Thus, components of a degradative machine have been harnessed to
      directly repress transcription.

PMID- 29446507
TI  - Technical determinants of biathlon standing shooting performance before and after
      race simulation.
AB  - The aim of this study was to identify performance-determining factors in biathlon
      standing shooting in rest and after intense exercise. Eight Finnish national- and
      nine junior-team biathletes participated in the study. Participants fired 40
      resting shots (REST) and 2 * 5 competition simulation shots (LOAD) after 5
      minutes of roller skiing at 95% of peak heart rate. Hit percentage, aiming point
      trajectory and postural balance were measured from each shot. Cleanness of
      triggering (ATV, movement of the aiming point 0-0.2 second before the shot) and
      vertical stability of hold (DevY) were the most important components affecting
      shooting performance both in REST (DevY, R = -0.61, P < .01; ATV, R = -0.65, P <
      .01) and in LOAD (DevY, R = -0.50, P < .05; ATV, R = -0.77, P < .001). Postural
      balance, especially in shooting direction, was related to DevY and ATV. Stability
      of hold in horizontal (F(1,15) = 7.025, P < .05) and vertical (F(1,15) = 21.285,
      P < .001) directions, aiming accuracy (F(1,15) = 9.060, P < .01), and cleanness
      of triggering (F(1,15) = 59.584, P < .001) decreased from REST to LOAD,
      accompanied by a decrease in postural balance. National- and junior-team
      biathletes differed only in hit percentage in REST (92 +/- 8% vs 81 +/- 8%, P <
      .05) and left leg postural balance in shooting direction in LOAD (0.31 +/- 0.18
      mm vs 0.52 +/- 0.20 mm, P < .05), and the intense exercise affected the shooting
      technical components similarly in both national and junior groups. Biathletes
      should focus on cleanness of triggering and vertical stability of hold in order
      to improve biathlon standing shooting performance. More stable postural balance
      in shooting direction could help to improve these shooting technical components.

PMID- 29446509
TI  - Recovery without autonomy: Progress forward or more of the same for mental health
      service users?
AB  - In Western nations, the Recovery approach has become a widely accepted philosophy
      and treatment concept in mental health. Yet, community understanding of the
      Recovery approach remains largely unexplored. This study aimed to investigate (i)
      people's awareness of the principles underpinning the Recovery approach in mental
      health, and (ii) the treatment approaches people consider most important, and
      whether these align with the Recovery approach. To achieve these aims, a random
      sample of 1217 Australian adults participated in the National Social Survey (QSS)
      via telephone interview. People's experience with mental health services, the
      importance they place on various treatment approaches, and their awareness of
      principles underpinning the Recovery approach were assessed. Analyses were
      conducted using descriptive statistics. Most participants (94%) agreed that
      'regardless of the severity of symptoms experienced and/or the mental illness
      diagnosis, being diagnosed with a mental illness means there is always hope for a
      meaningful life'. Moreover, most participants considered treatments in line with
      the Recovery approach as important. However, few participants (35%) agreed with
      the principle that 'after diagnosis, the person themselves should direct the long
      term management of their mental illness, rather than a medical professional'.
      Australian people were to some extent aware of the principles underpinning the
      Recovery Approach, particularly with regard to hope, ability to live a meaningful
      life, and the importance of support from family, friends, and others living with
      mental illness. Nonetheless, autonomy was not highly prioritized, with the
      prevailing view that management of mental illness should be directed by the
      medical profession.

PMID- 29446508
TI  - Accelerated T2 mapping combining parallel MRI and model-based reconstruction:
      GRAPPATINI.
AB  - BACKGROUND: Quantitative T2 measurements are sensitive to intra- and
      extracellular water accumulation and myelin loss. Therefore, quantitative T2
      promises to be a good biomarker of disease. However, T2 measurements require long
      acquisition times. PURPOSE: To accelerate T2 quantification and subsequent
      generation of synthetic T2 -weighted (T2 -w) image contrast for clinical research
      and routine. To that end, a recently developed model-based approach for rapid T2
      and M0 quantification (MARTINI) based on undersampling k-space, was extended by
      parallel imaging (GRAPPA) to enable high-resolution T2 mapping with access to T2 
      w images in less than 2 minutes acquisition time for the entire brain. STUDY
      TYPE: Prospective cross-sectional study. SUBJECTS/PHANTOM: Fourteen healthy
      subjects and a multipurpose phantom. FIELD STRENGTH/SEQUENCE: Carr-Purcell
      Meiboom-Gill sequence at a 3T scanner. ASSESSMENT: The accuracy and
      reproducibility of the accelerated T2 quantification was assessed. Validations
      comprised MRI studies on a phantom as well as the brain, knee, prostate, and
      liver from healthy volunteers. Synthetic T2 -w images were generated from
      computed T2 and M0 maps and compared to conventional fast spin-echo (SE) images.
      STATISTICAL TESTS: Root mean square distance (RMSD) to the reference method and
      region of interest analysis. RESULTS: The combination of MARTINI and GRAPPA
      (GRAPPATINI) lead to a 10-fold accelerated T2 mapping protocol with 1:44 minutes
      acquisition time and full brain coverage. The RMSD of GRAPPATINI increases less
      (4.3%) than a 10-fold MARTINI reconstruction (37.6%) in comparison to the
      reference. Reproducibility tests showed low standard deviation (SD) of T2 values
      in regions of interest between scan and rescan (<0.4 msec) and across subjects
      (<4 msec). DATA CONCLUSION: GRAPPATINI provides highly reproducible and fast
      whole-brain T2 maps and arbitrary synthetic T2 -w images in clinically compatible
      acquisition times of less than 2 minutes. These abilities are expected to support
      more widespread clinical applications of quantitative T2 mapping. LEVEL OF
      EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:359-368.

PMID- 29446510
TI  - Use of T1 relaxation time in rotating frame (T1 rho) and apparent diffusion
      coefficient to estimate cerebral stroke evolution.
AB  - BACKGROUND: The major factor for the appropriate treatment strategies for
      ischemia patients is its onset timing. PURPOSE/HYPOTHESIS: To study to evaluate
      the diagnostic accuracy of T1 relaxation time in a rotating frame (T1 rho) and
      apparent diffusion coefficient (ADC) from MRI to estimate ischemia stages. STUDY
      TYPE: Prospective. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: In all, 73
      patients (49 males, aged 29-78 years and 24 females, aged 22-94 years) with
      ischemia were prospectively imaged with T1 rho and diffusion MRI during the
      postischemic period. FIELD STRENGTH/SEQUENCE: 3T/T1 rho and diffusion-weighted
      imaging (DWI). ASSESSMENT: Ischemic parenchyma included tissue with elevated
      signal areas on DWI and correlative hypointense areas on ADC maps. STATISTICAL
      TESTS: The sensitivity of variables to ischemia time was quantified by analyzing
      the respective correlations of these values with onset time. RESULTS: DeltaT1 rho
      (ipsilateral-contralateral differences in T1 rho) (R2  = 0.956) and T1 rhoipsi
      (ipsilateral ischemia T1 rho values) (R2  = 0.941) were elevated in all ischemic
      lesions; these values increased linearly as a function of time, unlike DeltaADC
      (ipsilateral-contralateral differences in ADC) (R2  = -0.410) and ADCipsi
      (ipsilateral ischemia ADC values) (R2  = 0.550). DeltaT1 rho and T1 rhoipsi were
      significantly different between all stages (P < 0.01), except the acute and
      hyperacute stages (P = 0.589 for DeltaT1 rho, P = 0.290 for T1 rhoipsi ,
      respectively), but DeltaADC and ADCipsi only between the late subacute and early
      subacute stages (P < 0.01) and the late subacute and chronic stages (P < 0.01).
      DATA CONCLUSION: These data suggest that T1 rho can provide estimates for the
      ischemic time in patients. T1 rho has the potential to outperform diffusion for
      single-timepoint examination because the T1 rho change during strokes is positive
      and linear. If patients with suspected stroke are scanned by MRI within the
      appropriate timeframe, T1 rho may provide tools for evaluating stroke onset,
      potentially aiding in treatment strategies. LEVEL OF EVIDENCE: 4 Technical
      Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1247-1254.

PMID- 29446511
TI  - Long-term study of tubeless insulin pump therapy compared to multiple daily
      injections in youth with type 1 diabetes: Data from the German/Austrian DPV
      registry.
AB  - OBJECTIVE: To examine glycemic control in youth with type 1 diabetes (T1D) who
      switched from multiple daily injections (MDI) to a tubeless insulin pump (Omnipod
      Insulin Management System, Insulet Corporation, Billerica, Massachusetts)
      compared to patients who continued MDI therapy over a 3-year time period.
      RESEARCH DESIGN AND METHODS: This retrospective analysis of the German/Austrian
      Diabetes Patienten Verlaufsdokumentation registry included data from 263 centers
      and 2529 patients <20 years (n = 660 tubeless insulin pump; n = 1869 MDI) who
      initiated treatment on a tubeless insulin pump as of January 1, 2013 and had 1
      year of data preswitch from MDI and 3 years of data postswitch to a tubeless
      pump. Outcomes included the change in glycated hemoglobin (HbA1c), insulin dose,
      and body mass index (BMI) SD score (SDS). RESULTS: Youth with T1D who switched
      from MDI therapy to a tubeless insulin pump showed better glycemic control at 1
      year compared to patients who continued MDI treatment, adjusted mean +/- SE: 7.5%
      +/- 0.03% (58 mmol/mol) vs 7.7% +/- 0.02% (61 mmol/mol); P < .001, with no
      between-group difference at 2 and 3 years. Total daily insulin dose was lower (P
      < .001) in the tubeless insulin pump group, 0.80 +/- 0.01, 0.81 +/- 0.01, and
      0.85 +/- 0.01 U/kg, vs the MDI group, 0.89 +/- 0.01, 0.94 +/- 0.01, and 0.97 +/-
      0.01 U/kg, at 1, 2, and 3 years, respectively (all P < .001). BMI SDS increased
      in both groups and was not different over time. CONCLUSIONS: Treatment with a
      tubeless insulin pump in youth with T1D was associated with improvements in
      glycemic control compared to MDI after 1 year and appears to be an effective
      alternative to MDI.

PMID- 29446512
TI  - Nursing staff-led behavioural group intervention in psychiatric in-patient care:
      Patient and staff experiences.
AB  - A promising intervention in mental health in-patient care is behavioural
      activation (BA). Interventions based on BA can be used by mental health nurses
      and other staff members. The aim of this study was to evaluate patients' and
      staff members' experiences of a nursing staff-led behavioural group intervention
      in mental health in-patient care. The intervention was implemented at three adult
      acute general mental health in-patient wards in a public hospital setting in
      Sweden. A self-administrated questionnaire, completed by 84 patients and 34
      nurses and nurse assistants, was administered, and nonparametric data analysed
      using descriptive statistics. Our findings revealed that both patients and
      nursing staff ranked nursing care and care environment as important aspects in
      the recovery process. Patients and staff members reported overall positive
      experiences of the group sessions. Patients with higher frequencies of attendance
      and patients satisfied with overall care had a more positive attitude towards the
      intervention. A more positive experience of being a group leader was reported by
      staff members who had been leading groups more than ten times. The most common
      impeding factor during implementation, reported by staff members, was a negative
      attitude to change. Conducive factors were having support from a psychologist and
      the perception that patients were showing interest. These positive experiences
      reported by patients and nursing staff, combined with previous research in this
      field, are taking us one step further in evaluating group sessions based on BA as
      a meaningful nursing intervention in mental health in-patient care.

PMID- 29446513
TI  - A systematic review of clinical supervision evaluation studies in nursing.
AB  - According to the international, extant literature published during the last 20
      years or so, clinical supervision (CS) in nursing is now a reasonably common
      phenomenon. Nevertheless, what appears to be noticeably 'thin on the ground' in
      this body of literature are empirical evaluations of CS, especially those
      pertaining to client outcomes. Accordingly, the authors undertook a systematic
      review of empirical evaluations of CS in nursing to determine the state of the
      science. Adopting the approach documented by Stroup et al. (JAMA, 283, 2000,
      2008), the authors searched for reports of evaluation studies of CS in nursing -
      published during the years 1995 to 2015. Keywords for the search were 'clinical
      supervision', 'evaluation', 'efficacy', 'nursing', and combinations of these
      keywords. Electronic databases used were CINAHL, MEDLINE, PsychLIT, and the
      British Nursing Index. The research evidence from twenty-eight (28) studies
      reviewed is presented, outlining the main findings with an overview of each study
      presented. The following broad themes were identified and are each discussed in
      the study: narrative/anecdotal accounts of positive outcomes for clinical
      supervision, narrative/anecdotal accounts of negative outcomes for clinical
      supervision, empirical positive outcomes reported by supervisee, and empirical
      findings showing no effect by supervisee.

PMID- 29446515
TI  - Long-term monitoring of an amphibian community after a climate change- and
      infectious disease-driven species extirpation.
AB  - Infectious disease and climate change are considered major threats to
      biodiversity and act as drivers behind the global amphibian decline. This is, to
      a large extent, based on short-term studies that are designed to detect the
      immediate and strongest biodiversity responses to a threatening process. What few
      long-term studies are available, although typically focused on single species,
      report outcomes that often diverge significantly from the short-term species
      responses. Here, we report the results of an 18-year survey of an amphibian
      community exposed to both climate warming and the emergence of lethal
      chytridiomycosis. Our study shows that the impacts of infectious disease are
      ongoing but restricted to two out of nine species that form the community,
      despite the fact all species can become infected with the fungus. Climate warming
      appears to be affecting four out of the nine species, but the response of three
      of these is an increase in abundance. Our study supports a decreasing role of
      infectious disease on the community, and an increasing and currently positive
      effect of climate warming. We caution that if the warming trends continue, the
      net positive effect will turn negative as amphibian breeding habitat becomes
      unavailable as water bodies dry, a pattern that already may be underway.

PMID- 29446514
TI  - Giant cell-rich osteosarcoma of the vertebra with murine double minute chromosome
      2- and cyclin-dependent kinase 4-positive and histone H3F3A mutant p.Gly34Trp
      negative immunophenotypes.

PMID- 29446516
TI  - A rare case of uterine tumor resembling ovarian sex-cord tumor with necrosis and
      increased mitotic activity.

PMID- 29446517
TI  - Coumarin Photocaging Groups Modified with an Electron-Rich Styryl Moiety at the 3
      Position: Long-Wavelength Excitation, Rapid Photolysis, and Photobleaching.
AB  - A new class of coumarin photocaging groups modified with an electron-rich styryl
      moiety at the 3-position was constructed. The large pi-conjugated structure and
      stabilization of the carbocation intermediates by electron donors endowed the new
      photocaging groups with excellent long-wavelength absorption, large two-photon
      absorption cross-sections, and high uncaging quantum yields. Moreover, the new
      photocaging groups displayed unique photobleaching properties after photocleavage
      as a result of the intramolecular cyclization rearrangement of a carbocation
      intermediate to form five-membered ring byproducts and block the styryl
      conjugation at the 3-position. These superior properties of the new photocaging
      groups are extremely beneficial for high-concentration samples and thick
      specimens, thus extending the application of photocaging groups in many fields.

PMID- 29446518
TI  - Interwoven histories: Mental health nurses with experience of mental illness,
      qualitative findings from a mixed methods study.
AB  - The effects of mental health nurses' own experience of mental illness or being a
      carer have rarely been researched beyond the workplace setting. This study aimed
      to explore how the experience of mental illness affects mental health nurses'
      lives outside of and inside work. A sample of 26 mental health nurses with
      personal experience of mental illness took part in semistructured interviews.
      Data were analysed thematically using a six-phase approach. The analysis revealed
      the broad context of nurses' experiences of mental illness according to three
      interwoven themes: mental illness as part of family life; experience of accessing
      services; and life interwoven with mental illness. Participants typically
      described personal and familial experience of mental illness across their life
      course, with multiple causes and consequences. The findings suggest that nurses'
      lives outside of work should be taken into account when considering the impact of
      their personal experience of mental illness. Similarly being a nurse influences
      how mental illness is experienced. Treatment of nurses with mental illness should
      account for their nursing expertise whilst recognizing that the context for
      nurses' mental illness could be much broader than the effect of workplace stress.

PMID- 29446519
TI  - A plateau in new onset type 1 diabetes: Incidence of pediatric diabetes in the
      United States Military Health System.
AB  - OBJECTIVES: To describe the incidence and prevalence of type 1 diabetes among
      pediatric dependents of the US Department of Defense. METHODS: The Military
      Health System (MHS) data repository was used to identify pediatric patients (<=17
      years of age) with type 1 diabetes from January 1, 2007 to December 31, 2012.
      Annual incidence, annual prevalence and adjusted incidence were calculated and
      stratified by sex, age group, and region of residence. RESULTS: Within a 6-year
      study period from 2007 to 2012, 5616 pediatric patients with type 1 diabetes were
      identified; 57% male, mean (SD) age of 10.9 (4.2) years. Annual type 1 diabetes
      incidence (per 100 000 persons) over the 5-year time period ranged from 20.7/100
      000 to 21.3/100 000. Incidence for each year was highest in the 10 to 14 years
      age group and ranged from 30.9/100 000 in 2008 to 35.2/100 000 in 2011. Annual
      type 1 diabetes prevalence (per 1000 persons) remained stable throughout the
      study period at 1.5/1000. Adjusted incidence for males was significantly higher
      compared to females (21.0/100 000 vs 18.1/100 000; P = .001). During the study
      period, annual incidence remained steady (test for trend, P = .984). CONCLUSIONS:
      The incidence of type 1 diabetes among children appears to plateau during the
      study period, suggesting a steady state of type 1 diabetes within this pediatric
      population. The MHS provides an accurate and up to date look at incidence of type
      1 diabetes and may reflect broader trends of incidence of pediatric disease for
      the United States as a whole.

PMID- 29446520
TI  - Lenalidomide as a novel therapy for gastrointestinal angiodysplasia in von
      Willebrand disease.
AB  - INTRODUCTION: Lenalidomide is a thalidomide analog with anti-angiogenic
      properties. Previous case reports suggest its efficacy in preventing
      gastrointestinal bleeding (GIB) secondary to angiodysplasia (AD) in hereditary
      haemorrhagic telangiectasia and potentially in reversing AD. We present the first
      case series to explore lenalidomide as a treatment for AD-related GIB in patients
      with von Willebrand disease (VWD). METHODS: A retrospective chart review was
      conducted to include patients with VWD, who were evaluated from 2010 to 2013 and
      who had received lenalidomide to treat recurrent GIB secondary to AD. All
      patients had failed single-agent use of antifibrinolytic agents. Patients were
      observed for at least 2 years on therapy. RESULTS: Five patients (3 males; 68.2
      +/- 4.9 years) with VWD (3 with type 3 and 1 each with types 1 and 2a) and AD
      were found. Sites of AD included the stomach, duodenum, jejunum and colon.
      Lenalidomide was started at 5 mg oral daily. Uptitration to 10 and 15 mg in 1
      patient each was necessary due to recurrence of GIB. The mean number of
      endoscopies performed for control of GIB post lenalidomide was significantly
      lower compared to pretherapy (0.25 vs 5.50; P = .001). Mean bleed-free duration
      on lenalidomide was 12.6 +/- 4.7 months. Three patients have reported no GIB on
      lenalidomide. CONCLUSION: This case series demonstrates significantly reduced
      number of endoscopies and increased bleed-free duration with lenalidomide
      treatment in selected patients with VWD and recurrent GIB from AD. Prospective
      multicenter trials are needed to further define the role of lenalidomide in the
      management of GIB from angiodysplasia and VWD.

PMID- 29446521
TI  - Co-assembly of Polyoxometalates and Zwitterionic Amphiphiles into Supramolecular
      Hydrogels: From Crystalline Fibrillar to Amorphous Micellar Networks.
AB  - Gelation mechanism is of utmost importance to the rational design of
      supramolecular hydrogelators. Although both kinetic and thermodynamic controlled
      self-assembly processes have been widely studied in hydrogels, the formation
      relationship between crystalline and amorphous gel networks still remains
      ambiguous. Herein, a gelation transformation from a kinetic to a thermodynamic
      process was achieved by balancing the rigidity and flexibility of the inorganic
      organic co-assemblies. By using polyoxometalates and zwitterionic amphiphiles,
      the transition morphologies between crystalline and amorphous hydrogel networks
      were evidenced for the first time, as ordered wormlike micelles. Given the
      versatile applications of hydrogels in biological systems and materials science,
      these findings may highlight the potential of inorganic-organic binary
      supramolecular hydrogelators and fill in the blank between kinetic and
      thermodynamic controlled gelation processes.

PMID- 29446522
TI  - A dedifferentiated liposarcoma with inflammatory myofibroblastic tumor-like
      features.

PMID- 29446523
TI  - Safety and tolerability of dapagliflozin, saxagliptin and metformin in
      combination: Post-hoc analysis of concomitant add-on versus sequential add-on to
      metformin and of triple versus dual therapy with metformin.
AB  - The safety of triple oral therapy with dapagliflozin plus saxagliptin plus
      metformin versus dual therapy with dapagliflozin or saxagliptin plus metformin
      was compared in a post-hoc analysis of 3 randomized trials of sequential or
      concomitant add-on of dapagliflozin and saxagliptin to metformin. In the
      concomitant add-on trial, patients with type 2 diabetes on stable metformin
      received dapagliflozin 10 mg/d plus saxagliptin 5 mg/d. In sequential add-on
      trials, patients on metformin plus either saxagliptin 5 mg/d or dapagliflozin 10
      mg/d received dapagliflozin 10 mg/d or saxagliptin 5 mg/d, respectively, as add
      on therapy. After 24 weeks, incidences of adverse events and serious adverse
      events were similar between triple and dual therapy and between concomitant and
      sequential add-on regimens. Urinary tract infections were more common with
      sequential than with concomitant add-on therapy; genital infections were reported
      only with sequential add-on of dapagliflozin to saxagliptin plus metformin.
      Hypoglycaemia incidence was <2.0% across all analysis groups. In conclusion, the
      safety and tolerability of triple therapy with dapagliflozin, saxagliptin and
      metformin, as either concomitant or sequential add-on, were similar to dual
      therapy with either agent added to metformin.

PMID- 29446524
TI  - Impact of blood flow-restricted bodyweight exercise on skeletal muscle
      adaptations.
AB  - This study ascertains the ability of bodyweight blood flow-restricted (BFR)
      exercise training to promote skeletal muscle adaptations of significance for
      muscle accretion and metabolism. Six healthy young individuals (three males and
      three females) performed six weeks of bodyweight BFR training. Each session
      consisted of five sets of sit-to-stand BFR exercise to volitional failure with 30
      second inter-set recovery. Prior to, and at least 72 h after training, muscle
      biopsies were taken from m. vastus lateralis to assess changes in fibre type
      specific cross-sectional area (CSA), satellite cell (SC) and myonuclei content
      and capillarization, as well as mitochondrial protein expression. Furthermore,
      magnetic resonance imaging was used to assess changes in whole thigh muscle CSA.
      Finally, isometric knee extensor muscle strength was evaluated. An increase in
      knee extensor whole muscle CSA was observed at middle and distal localizations
      after training (3.2% and 3.5%, respectively) (P<0.05), and a trend was observed
      towards an increase in type I fibre CSA, whereas muscle strength did not
      increase. Additionally, the number of SCs and myonuclei associated with type I
      fibres increased by 65.7% and 20%, respectively (P<0.05). No significant changes
      were observed in measures of muscle capillarization and mitochondrial proteins.
      In conclusion, six weeks of bodyweight-based BFR exercise promoted myocellular
      adaptations related to muscle accretion, but not metabolic properties. Moreover,
      the study revealed that an appropriate total training volume needs further
      investigation before recommending bodyweight BFR to patient populations.

PMID- 29446526
TI  - The SCN9A channel and plasma membrane depolarization promote cellular senescence
      through Rb pathway.
AB  - Oncogenic signals lead to premature senescence in normal human cells causing a
      proliferation arrest and the elimination of these defective cells by immune
      cells. Oncogene-induced senescence (OIS) prevents aberrant cell division and
      tumor initiation. In order to identify new regulators of OIS, we performed a loss
      of-function genetic screen and identified that the loss of SCN9A allowed cells to
      escape from OIS. The expression of this sodium channel increased in senescent
      cells during OIS. This upregulation was mediated by NF-kappaB transcription
      factors, which are well-known regulators of senescence. Importantly, the
      induction of SCN9A by an oncogenic signal or by p53 activation led to plasma
      membrane depolarization, which in turn, was able to induce premature senescence.
      Computational and experimental analyses revealed that SCN9A and plasma membrane
      depolarization mediated the repression of mitotic genes through a calcium/Rb/E2F
      pathway to promote senescence. Taken together, our work delineates a new pathway,
      which involves the NF-kappaB transcription factor, SCN9A expression, plasma
      membrane depolarization, increased calcium, the Rb/E2F pathway and mitotic gene
      repression in the regulation of senescence. This work thus provides new insight
      into the involvement of ion channels and plasma membrane potential in the control
      of senescence.

PMID- 29446527
TI  - Nonbinary quantification technique accounting for myocardial infarct
      heterogeneity: Feasibility of applying percent infarct mapping in patients.
AB  - BACKGROUND: Binary threshold-based quantification techniques ignore myocardial
      infarct (MI) heterogeneity, yielding substantial misquantification of MI.
      PURPOSE: To assess the technical feasibility of MI quantification using percent
      infarct mapping (PIM), a prototype nonbinary algorithm, in patients with
      suspected MI. STUDY TYPE: Prospective cohort POPULATION: Patients (n = 171) with
      suspected MI referred for cardiac MRI. FIELD STRENGTH/SEQUENCE: Inversion
      recovery balanced steady-state free-precession for late gadolinium enhancement
      (LGE) and modified Look-Locker inversion recovery (MOLLI) T1 -mapping on a 1.5T
      system. ASSESSMENT: Infarct volume (IV) and infarct fraction (IF) were quantified
      by two observers based on manual delineation, binary approaches (2-5 standard
      deviations [SD] and full-width at half-maximum [FWHM] thresholds) in LGE images,
      and by applying the PIM algorithm in T1 and LGE images (PIMT1 ; PIMLGE ).
      STATISTICAL TEST: IV and IF were analyzed using repeated measures analysis of
      variance (ANOVA). Agreement between the approaches was determined with Bland
      Altman analysis. Interobserver agreement was assessed by intraclass correlation
      coefficient (ICC) analysis. RESULTS: MI was observed in 89 (54.9%) patients, and
      185 (38%) short-axis slices. IF with 2, 3, 4, 5SDs and FWHM techniques were 15.7
      +/- 6.6, 13.4 +/- 5.6, 11.6 +/- 5.0, 10.8 +/- 5.2, and 10.0 +/- 5.2%,
      respectively. The 5SD and FWHM techniques had the best agreement with manual IF
      (9.9 +/- 4.8%) determination (bias 1.0 and 0.2%; P = 0.1426 and P = 0.8094,
      respectively). The 2SD and 3SD algorithms significantly overestimated manual IF
      (9.9 +/- 4.8%; both P < 0.0001). PIMLGE measured significantly lower IF (7.8 +/-
      3.7%) compared to manual values (P < 0.0001). PIMLGE , however, showed the best
      agreement with the PIMT1 reference (7.6 +/- 3.6%, P = 0.3156). Interobserver
      agreement was rated good to excellent for IV (ICCs between 0.727-0.820) and fair
      to good for IF (0.589-0.736). DATA CONCLUSION: The application of the PIMLGE
      technique for MI quantification in patients is feasible. PIMLGE , with its
      ability to account for voxelwise MI content, provides significantly smaller IF
      than any thresholding technique and shows excellent agreement with the T1 -based
      reference. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson.
      Imaging 2018.

PMID- 29446528
TI  - Can CT imaging features of ground-glass opacity predict invasiveness? A meta
      analysis.
AB  - BACKGROUND: A meta-analysis was conducted to investigate the diagnostic
      performance of computed tomography (CT) imaging features of ground-glass opacity
      (GGO) to predict invasiveness. METHODS: Two reviewers independently searched
      PubMed, Medline, Web of Science, Cochrane Embase and CNKI for relevant studies.
      CT imaging signs of bubble lucency, speculation, lobulated margin, and pleural
      indentation were used as diagnostic references to discriminate pre-invasive and
      invasive disease. The sensitivity, specificity, diagnostic odds ratio (DOR),
      summary receiver operating characteristic (SROC) curves, and the area under the
      SROC curve (AUC) were calculated to evaluate diagnostic efficiency. RESULTS:
      Twelve studies were finally included. Diagnostic performance ranged from 0.41 to
      0.52 for sensitivity and 0.56 to 0.63 for specificity. The diagnostic positive
      and negative likelihood ratios ranged from 1.03 to 2.13 and 0.52 to 1.05,
      respectively. The DORs of the GGO CT features for discriminating invasive disease
      ranged from 1.02 to 4.00. The area under the ROC curve was also low, with a range
      of 0.60 to 0.67 for discriminating pre-invasive and invasive disease. CONCLUSION:
      The diagnostic value of a single CT imaging sign of GGO, such as bubble lucency,
      speculation, lobulated margin, or pleural indentation is limited for
      discriminating pre-invasive and invasive disease because of low sensitivity,
      specificity, and AUC.

PMID- 29446525
TI  - Laboratory testing for factor VIII and IX inhibitors in haemophilia: A review.
AB  - Inhibitors are antibodies directed against haemophilia treatment products which
      interfere with their function. Factor VIII (FVIII) inhibitors in haemophilia A
      and factor IX (FIX) inhibitors in haemophilia B are significant clinically when
      they require a change in a patient's treatment regimen. Their persistence may
      increase morbidity and mortality. Multiple laboratory tests are now available for
      detecting and understanding inhibitors in haemophilia. Inhibitors are
      traditionally measured by their interference in clotting or chromogenic factor
      assays. They may also be detected using immunologic assays, such as enzyme-linked
      immunosorbent assay or fluorescence immunoassay. Anti-FVIII or anti-FIX
      antibodies of IgG4 subclass best correlate with the presence of functional
      inhibitors. Improvements in inhibitor measurement have been recently introduced.
      Preanalytical heat treatment of patient specimens allows testing of patients
      without delaying treatment. Use of chromogenic and immunologic assays may aid in
      identification of false-positive results, which are frequent among low-titre
      inhibitors. Validated reagent substitutions can be used to reduce assay cost. New
      methods for defining assay positivity and reporting low-titre inhibitors have
      been suggested. Challenges remain in the areas of quality control, assay
      standardization, monitoring of patients undergoing immune tolerance induction
      therapy and testing in the presence of modified and novel treatment products.

PMID- 29446529
TI  - Educational disparities in the associations between self-monitoring of blood
      glucose and glycemic control in type 2 diabetes patients in Xiamen, China.
AB  - BACKGROUND: This study examined the combined effects of self-monitoring of blood
      glucose (SMBG) and educational attainment on glycemic control in type 2 diabetes
      mellitus (T2DM) patients. METHODS: A cross-sectional survey was performed among
      community residents with T2DM. Good glycemic control was defined as HbA1c <7% in
      the most recent measurement. Multivariable logistic regression was used to
      examine associations of glycemic control with SMBG, educational attainment, and
      their combined effects by controlling for certain covariates, with further
      stratification by sex. RESULTS: Complete data were available for 798 patients, of
      which 58.52% had good glycemic control. Higher education and SMBG were associated
      with good glycemic control (P < 0.05). In the SMBG group, tertiary-educated
      patients had the greatest odds of good glycemic control (odds ratios 2.56; 95%
      confidence interval 1.31-4.99). Among those performing SMBG, the odds of good
      glycemic control were higher for those with higher education levels (Ptrend  =
      0.003), whereas there was no clear trend for those not performing SMBG (Ptrend  =
      0.071). For subjects attaining secondary and tertiary education levels, the odds
      of good glycemic control were higher in those performing SMBG, although there was
      no significant difference between the two groups for those with a primary
      education. Glycemic control decreased slightly among males with a primary level
      education, but showed an increasing trend among females with a primary level
      education. CONCLUSIONS: Sex-specific educational disparities exist in the
      association between SMBG and glycemic control. More detailed guidelines for SMBG
      according to a subject's socioeconomic position and sex are required.

PMID- 29446530
TI  - A novel tissue-based beta-catenin gene and immunohistochemical analysis to
      exclude familial adenomatous polyposis among children with hepatoblastoma tumors.
AB  - BACKGROUND: The Wnt/beta-catenin pathway plays a central role in the pathogenesis
      of most hepatoblastomas (HBs), that is, up to 60-80% carry activating CTNNB1
      mutations. HBs can however also be the first manifestation of familial
      adenomatous polyposis (FAP). As this is a severe disease, it is important for the
      patient and related family members to firmly exclude FAP at an early stage.
      Current diagnosis largely depends on APC germline mutation detection on genomic
      DNA, which is associated with 10-20% false-negative results. Here, we establish
      and validate a tissue-based beta-catenin gene and immunohistochemical analysis,
      which complements germline mutation screening to exclude the diagnosis of FAP
      among HB patients. METHODS: Tumor tissues of 18 HB patients, including three FAP
      cases were subjected to CTNNB1 exon 3 mutational analysis and
      immunohistochemistry comparing staining patterns for total and exon 3 specific
      beta-catenin antibodies. RESULTS: Our novel tissue-based method reliably
      identified all three FAP patients. Their tumors were characterized by a wild-type
      exon 3 sequence and a comparable nuclear staining for both antibodies. In
      contrast, the non-FAP tumors carried missense CTNNB1 mutations combined with a
      clearly reduced staining for the exon 3 antibody, or complete loss of staining in
      case of lesions with exon 3 deletions. CONCLUSION: We have successfully
      established and validated a novel beta-catenin gene and immunohistochemical
      diagnostic method, which, when combined with routine germline DNA testing, allows
      the exclusion of the diagnosis of FAP among HB patients.

PMID- 29446531
TI  - A Valorization of White Settler Nationalism? The Canadian Sesquicentennial
      Anniversary.

PMID- 29446532
TI  - Foreword.

PMID- 29446533
TI  - Forms of Capital and Habitus in the Decision to Go on Academic Exchange.
AB  - Although Canadian universities have made internationalization a strategic
      priority, only few Canadian students currently participate in any international
      study opportunities. Drawing on interviews with Canadian students who were about
      to spend some of their undergraduate education abroad as exchange students, or
      had recently returned from a study exchange, we argue that despite the importance
      of relatively high costs associated with international study experiences,
      cultural factors play a more important role in enabling the decision to study
      abroad. Being habitually exposed to travel in one's family, and having been
      encouraged to travel independently as a teenager or young adult emerge as
      important precursors to our participants' decision to take part in study
      exchanges. Although one needs to engage critically with university
      administrators' current preoccupation with internationalization, being exposed to
      an extended time abroad has shown to have positive effects, especially for
      otherwise underprivileged students. Given the exploratory nature of this study,
      we conclude with suggestions for further research aimed at confirming our
      findings and developing policy.

PMID- 29446534
TI  - Habitat Maintenance and Local Economic Ethics in Rural Atlantic Canada.
AB  - Inspired by Jane Jacobs's writing on "habitat maintenance," this paper seeks to
      identify the ethics that sometimes compel rural residents to act in ways that
      preserve their communities in the long run, despite short-term incentives to do
      otherwise. Data from focus groups in four rural Atlantic Canadian communities
      suggest shared ethics around entrepreneurship, market competition, buying local,
      and subsistence, some of which underlie the rural practices and perspectives that
      appear, to some outsiders, as irrational and "backwards." Understanding these
      ethics and the practices they incite as components of habitat maintenance-and
      judging them by their situated pragmatism rather than their fit with the
      placeless ideologies of growth-centric global capitalism and competitiveness
      highlights their rationality and utility. Findings could help direct discussions
      of rural economic development toward notions of prosperity, sustainability, and
      economy that fit better with rural realities.

PMID- 29446535
TI  - Translocality, Network Structure, and Music Worlds: Underground Metal in the
      United Kingdom.
AB  - Translocal music worlds are often defined as networks of local music worlds.
      However, their networked character and more especially their network structure is
      generally assumed rather than concretely mapped and explored. Formal social
      network analysis (SNA) is beginning to attract interest in music sociology but it
      has not previously been used to explore a translocal music world. In this paper,
      drawing upon a survey of the participation of 474 enthusiasts in 148 live music
      events, spread across 6 localities, we use SNA to explore a significant "slice"
      of the network structure of the U.K.'s translocal underground heavy metal world.
      Translocality is generated in a number of ways, we suggest, but one way, the way
      we focus upon, involves audiences traveling between localities to attend gigs and
      festivals. Our analysis of this network uncovers a core-periphery structure
      which, we further find, maps onto locality. Not all live events enjoy equal
      standing in our music world and some localities are better placed to capture more
      prestigious events, encouraging inward travel. The identification of such
      structures, and the inequality they point to, is, we believe, one of several
      benefits of using SNA to analyze translocal music worlds.

PMID- 29446536
TI  - Note on Language Correction in November 2017 issue of Canadian Review of
      Sociology/Revue Canadienne de Sociologie.

PMID- 29446537
TI  - Replacing the Canadianization Generation: An Examination of Faculty Composition
      from 1977 through 2017.
AB  - Amid growing numbers of doctoral graduates entering an increasingly competitive
      global academic job market, concerns about equity in the hiring process and the
      value of the Canadian Ph.D. are mounting. Grounded within the historical context
      of the Canadianization Movement, we examine the doctoral credentials of 4,934 U15
      social science faculty between 1977 and 2017 to understand the ebb and flow of
      incoming and outgoing faculty across the country's academic field. Our trend
      analyses reveal an overall increase in the proportion of Canadian-trained faculty
      hires with the noted exceptions of Canada's top three universities who display a
      strong presence of high-status American-trained faculty throughout. Results from
      the contemporary period, between 1997 and 2017, reveal a time of retirement
      during which outgoing Canadian-trained faculty are replaced with increasing
      proportions of American-trained academics.

PMID- 29446538
TI  - Islamophobia in Canada: Measuring the Realities of Negative Attitudes Toward
      Muslims and Religious Discrimination.
AB  - There has been growing discussion surrounding the phenomenon of Islamophobia in
      Western societies over the last few years. However, in-depth empirical research
      of the prevalence and patterns of prejudice toward Muslims remains scarce,
      especially in the Canadian context. With data from the 2011 Canadian Election
      Study and the 2014 General Social Survey, this study measures the extent to which
      negative feelings toward Muslims are present among the general adult population,
      and the extent to which Muslim Canadians themselves say they have experienced
      discrimination in recent years due to their religion, ethnicity, and culture.

PMID- 29446539
TI  - Corrigendum.

PMID- 29446540
TI  - The Institution of Sociological Theory in Canada.
AB  - Using theory syllabi and departmental data collected for three academic years,
      this paper investigates the institutional practice of theory in sociology
      departments across Canada. In particular, it examines the position of theory
      within the sociological curriculum, and how this varies among universities. Taken
      together, our analyses indicate that theory remains deeply institutionalized at
      the core of sociological education and Canadian sociologists' self-understanding;
      that theorists as a whole show some coherence in how they define themselves, but
      differ in various ways, especially along lines of region, intellectual
      background, and gender; that despite these differences, the classical versus
      contemporary heuristic largely cuts across these divides, as does the strongly
      ingrained position of a small group of European authors as classics of the
      discipline as a whole. Nevertheless, who is a classic remains an unsettled
      question, alternatives to the "classical versus contemporary" heuristic do exist,
      and theorists' syllabi reveal diverse "others" as potential candidates. Our
      findings show that the field of sociology is neither marked by universal
      agreement nor by absolute division when it comes to its theoretical
      underpinnings. To the extent that they reveal a unified field, the findings
      suggest that unity lies more in a distinctive form than in a distinctive content,
      which defines the space and structure of the field of sociology.

PMID- 29446541
TI  - Group-Based Diet and Physical Activity Weight-Loss Interventions: A Systematic
      Review and Meta-Analysis of Randomised Controlled Trials.
AB  - BACKGROUND: Many weight-loss interventions are delivered in groups but evidence
      on their effectiveness, and characteristics associated with effectiveness, is
      limited. We synthesised evidence on (1) design and delivery of group-based weight
      loss interventions; (2) effectiveness; and (3) associations between intervention
      characteristics, change techniques, and effectiveness. METHODS: Five online
      databases were searched to May 2017 for randomised controlled trials (RCTs) of
      group-based diet and/or physical activity interventions for overweight/obese
      adults (BMI >= 25). Intervention characteristics were synthesised narratively.
      Mean differences (MD) in weight loss were calculated using a random-effects meta
      analysis, and sub-group analyses were conducted to identify moderators of
      effectiveness. RESULTS: Forty-seven RCTs reporting 60 evaluations of group-based
      interventions were included. MD in weight loss between intervention and control
      groups was -3.49 [95% CI -4.15, -2.84], -3.44 [-4.23, -2.85], and -2.56 kg [
      3.79, -1.33] at follow-ups closest to 6, 12, and 24 months, respectively.
      Explicitly targeting weight loss, men-only groups providing feedback and dietary
      goals were significantly associated with greater effectiveness (p < .05).
      CONCLUSIONS: Diet and physical activity interventions delivered in groups are
      effective in promoting clinically meaningful weight loss at 12 months.
      Intervention design and effectiveness vary considerably between studies, and
      evidence on what optimises the effectiveness of group-based weight-loss
      interventions remains limited.

PMID- 29446542
TI  - Novel calcitonin gene-related peptide/chitosan-strontium-calcium phosphate
      cement: Enhanced proliferation of human umbilical vein endothelial cells in
      vitro.
AB  - Bone cement materials have some disadvantages, including slow degradation and no
      biological activity, which greatly weakens their clinical application. Therefore,
      the search for a multifunctional bioactive bone cement has become urgent. In this
      study, a novel bone cement sample of calcitonin gene-related peptide
      (CGRP)/chitosan-strontium (Sr)-calcium phosphate cement (CPC) was developed. The
      structure and morphology were observed by scanning electron microscope (SEM). The
      cytotoxicity and proliferation of CGRP/chitosan-Sr-CPC were also measured. The
      expression of CGRP receptor 1 was measured using an immunofluorescence assay.
      Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay
      (ELISA) were employed to quantify the VEGF mRNA and protein levels, respectively.
      Finally, the ability of the material to improve angiogenesis was assessed by
      using human umbilical vein endothelial cells (HUVECs) tube formation assay. The
      results showed that CGRP/Chitosan-Sr-CPC had the characteristics of a good
      orthopedic material without showing cell cytotoxicity to HUVECs. Meanwhile,
      CGRP/chitosan-Sr-CPC could release CGRP and enhance the proliferation of HUVECs
      via CGRP receptors. Moreover, CGRP/chitosan-Sr-CPC significantly upregulated the
      expression of the VEGF gene and protein in HUVECs, which might help improve the
      angiogenesis microenvironment. Besides, CGRP/chitosan-Sr-CPC could significantly
      improve angiogenesis of HUVECs. These findings provide new therapeutic material
      for the treatment of osteoporotic bone injury. (c) 2018 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29446543
TI  - Cyclin dependent kinase inhibitor 2A/B gene deletions are markers of poor
      prognosis in Indian children with acute lymphoblastic leukemia.
AB  - BACKGROUND: Cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) genes are
      implicated in many malignancies including acute lymphoblastic leukemia (ALL).
      These tumor suppressor genes, with a key regulatory role in cell cycle are
      located on chromosome 9p21.3. Previous studies involving CDKN2A/B gene deletions
      have shown mixed associations with survival outcome in childhood ALL. PROCEDURE:
      Hundred and four newly diagnosed children with ALL (1-14 years) were enrolled in
      this study. Genomic DNA from pretreatment bone marrow/peripheral blood samples of
      these children was investigated for copy number alterations in CDKN2A/B genes
      using multiplex ligation dependent probe amplification assay. Immunophenotype
      subtyping and cytogenetic and molecular analysis of ALL was performed at start of
      induction chemotherapy in all children. Children were monitored for response to
      prednisolone (Day 8), complete morphological remission, and minimal residual
      disease at the end of induction. The minimum postinduction follow-up period was 6
      months. RESULTS: CDKN2A/B deletions were seen in 19.8% (18/91) of B lineage acute
      lymphoblastic leukemia (B-ALL) and 38.5% (5/13) of T lineage acute lymphoblastic
      leukemia (T-ALL). Monoallelic CDKN2A/B deletions were found in 61.1% of total
      deletions in B-ALL while all the children with T-ALL harbored biallelic
      deletions. The prevalence of CDKN2A/B gene deletions was found to be
      significantly higher in older children (P = 0.002), in those with higher
      leukocyte count (P = 0.037), and in National Cancer Institute high risk group
      patients (P = 0.001) in the B-ALL subgroup. Hazard ratio was significantly high
      for children with CDKN2A/B deletions in total cohort (P = 0.004). Children with
      CDKN2A/B deletion had significantly lesser event free survival (P = 0.03).
      CONCLUSIONS: CDKN2A/B deletions were significantly more prevalent in T-ALL
      subgroup and were found to have higher hazard ratio and lesser event free
      survival in total cohort in our study.

PMID- 29446545
TI  - From Aqueous Dispersions to Functional Materials: Capillarity and Electrostatic
      Adhesion.
AB  - The author was first acquainted with polymer lattices as model particles for
      studying sedimentation phenomena, evolving towards the elucidation of synthetic
      and natural latex heterogeneity and microchemistry. This brought new elements to
      understand the remarkable mechanical properties of natural rubber, leading to the
      latex route for making nanocomposites. These materials show exceptional
      properties that are largely due to electrostatic adhesion, a concept that had
      been previously presented by Deryagin but was later abandoned. Electrostatic
      adhesion is the outcome of ion partition and self-assembly within drying aqueous
      dispersions, producing co-existing domains with opposite charges. Their
      examination allowed several experimental observations leading to the proposal of
      mechanisms to explain hitherto challenging electrostatic phenomena shown by
      solids and liquids. Water plays a decisive role in all the different phenomena
      described in this account.

PMID- 29446544
TI  - Association between plasma trans-fatty acid concentrations and diabetes in a
      nationally representative sample of US adults.
AB  - BACKGROUND: A diet high in trans-fatty acids (TFA) induces insulin resistance in
      rodent models and primates. However, previous epidemiological studies on the
      association between TFAs, based primarily on self-reported intake from the diet,
      and diabetes in humans have yielded conflicting results. Herein we examined the
      associations of objectively measured plasma TFA concentrations with diabetes in a
      large population-based study among US adults. METHODS: We included 3801
      participants aged >=20 years from the National Health and Nutrition Examination
      Survey 1999-2000 and 2009-10. Four major TFAs, namely palmitelaidic acid (C16:1 n
      7t), elaidic acid (C18:1 n-9t), vaccenic acid (C18:1 n-7t), and linolelaidic acid
      (C18:2 n-6t, 9t), were measured in fasting plasma using gas chromatography-mass
      spectrometry. Diabetes was defined by self-reported physician diagnosis, plasma
      fasting glucose >=126 mg/dL, or HbA1c >=6.5%. RESULTS: After adjustment for other
      major risk factors, the odds ratios (95% confidence intervals) of diabetes
      comparing the highest with lowest quintile of plasma TFAs was 2.19 (1.27-3.79)
      for total TFAs (Ptrend  = 0.01), 2.34 (1.48-3.72) for elaidic acid (Ptrend  =
      0.0004), 1.33 (0.82-2.15) for linolelaidic acid (Ptrend  = 0.18), 1.58 (0.97
      2.58) for palmitelaidic acid (Ptrend  = 0.02), and 1.64 (0.95-2.84) for vaccenic
      acid (Ptrend  = 0.08). In addition, total TFAs, elaidic acid, palmitelaidic acid,
      and vaccenic acid were significantly associated with fasting glucose, fasting
      insulin, the insulin resistance index, and HbA1c. CONCLUSIONS: In a nationally
      representative population, plasma TFAs, in particular elaidic acid, were
      positively associated with diabetes and biomarkers of glucose metabolism.

PMID- 29446546
TI  - De novo variants in Myelin regulatory factor (MYRF) as candidates of a new
      syndrome of cardiac and urogenital anomalies.
AB  - Myelin Regulatory Factor (MYRF) is a transcription factor that has previously
      been associated with the control of the expression of myelin-related genes.
      However, it is highly expressed in human tissues and mouse embryonic tissues
      outside the nervous system such as the stomach, lung, and small intestine. It has
      not previously been reported as a cause of any Mendelian disease. We report here
      two males with Scimitar syndrome [MIM 106700], and other features including
      penoscrotal hypospadias, cryptorchidism, pulmonary hypoplasia, tracheal
      anomalies, congenital diaphragmatic hernia, cleft spleen, thymic involution, and
      thyroid fibrosis. Gross neurologic functioning appears to be within normal
      limits. In both individuals a de novo variant in MYRF was identified using exome
      sequencing. Neither variant is found in gnomAD. Heterozygous variants in MYRF
      should be considered in patients with variants of Scimitar syndrome and
      urogenital anomalies.

PMID- 29446547
TI  - Promoting Ethylene Selectivity from CO2 Electroreduction on CuO Supported onto
      CO2 Capture Materials.
AB  - Cu is a unique catalyst for CO2 electroreduction, since it can catalyze CO2
      reduction to a series of hydrocarbons, alcohols, and carboxylic acids.
      Nevertheless, such Cu catalysts suffer from poor selectivity. High pressure of
      CO2 is considered to facilitate the activity and selectivity of CO2 reduction.
      Herein, a new strategy is presented for CO2 reduction with improved C2 H4
      selectivity on a Cu catalyst by using CO2 capture materials as the support at
      ambient pressure. N-doped carbon (Nx C) was synthesized through high-temperature
      carbonization of melamine and l-lysine. We observed that the CO2 uptake capacity
      of Nx C depends on both the microporous area and the content of pyridinic N
      species, which can be controlled by the carbonization temperature (600-800 
      degrees C). The as-prepared CuO/Nx C catalysts exhibit a considerably higher C2
      H4 faradaic efficiency (36 %) than CuO supported on XC-72 carbon black (19 %), or
      unsupported CuO (20 %). Moreover, there is a good linear relationship between the
      C2 H4 faradaic efficiency and CO2 uptake capacity of the supports for CuO. The
      local high CO2 concentration near Cu catalysts, created by CO2 capture materials,
      was proposed to increase the coverage of CO intermediate, which is favorable for
      the coupling of two CO units in the formation of C2 H4 . This study demonstrates
      that pairing Cu catalysts with CO2 capture supports is a promising approach for
      designing highly effective CO2 reduction electrocatalysts.

PMID- 29446548
TI  - A 12-h combined physical and psychological treatment programme for patients with
      persistent back pain.
AB  - This service evaluation analysed the long-term clinical outcomes, as measured by
      the Pain Self-Efficacy Questionnaire (PSEQ) and Oswestry Disability Index (ODI),
      of a 12-h group-based, multidisciplinary, combined physical and psychological
      treatment programme for patients with persistent back pain in a secondary care
      setting. Between April 2012 and December 2015, 373 patients attended the
      programme, with outcome measures obtained for 272 patients post-treatment. We
      randomly selected 120 patients who had completed treatment, for long-term outcome
      measurement follow-up, and gained outcome measures for 40 patients in total. At a
      median follow-up of 27 months post-treatment, the results demonstrated
      significant improvements in both clinical outcome measures. We conclude that a
      brief combined physical and psychological treatment programme appears to be
      effective at reducing back disability and pain self-efficacy, with improvements
      maintained in the longer term.

PMID- 29446549
TI  - Transition-Metal-Catalyzed Cyanation by Using an Electrophilic Cyanating Agent, N
      Cyano-N-phenyl-p-toluenesulfonamide (NCTS).
AB  - The ability to introduce a nitrile group into a biologically active compound is
      very useful in organic synthesis, owing to the importance of nitrile groups in
      transformations and tuning molecular properties. To date, nucleophilic cyanation
      has been the most used strategy for this purpose, whilst electrophilic cyanation
      reactions are less developed. Recently, the electrophilic cyanation reagent N
      cyano-N-phenyl-p-toluenesulfonamide (NCTS) has received increasing attention,
      owing to its superior properties in terms of safety and practicality. This Focus
      Review summarizes recent progress in transition-metal-catalyzed cyanation
      reactions that use NCTS.

PMID- 29446550
TI  - Impact of workplace violence against nurses' thriving at work, job satisfaction
      and turnover intention: A cross-sectional study.
AB  - AIMS AND OBJECTIVES: To investigate the interrelationships between workplace
      violence, thriving at work and turnover intention among Chinese nurses and to
      explore the action mechanism among these variables. BACKGROUND: Workplace
      violence is a dangerous occupational hazard globally, and it is pervasive in the
      health service industry. As a corollary, workplace violence may produce many
      negative outcomes among nursing staff. Consequently, it hinders nurses'
      professional performance and reduces nursing quality. DESIGN: A cross-sectional
      online survey was conducted. METHODS: A total of 1,024 nurses from 26 cities in
      China were recruited from February-May 2016. An anonymous questionnaire was used
      in this survey. Participants' completed data were collected using a demographics
      form and a 26-item questionnaire consisting of scales addressing workplace
      violence, thriving at work, job satisfaction, subjective well-being and turnover
      intention. To evaluate multivariate relationships, some multiple linear
      hierarchical regression analyses were performed. RESULTS: Workplace violence
      significantly negatively influenced nurses' job satisfaction and thriving at
      work, and significantly positively influenced nurses' turnover intention. Job
      satisfaction significantly predicted thriving at work and turnover intention. Job
      satisfaction not only fully mediated the relationship between workplace violence
      and thriving at work, but also partially mediated the relationship between
      workplace violence and turnover intention. Subjective well-being moderated the
      relationship between workplace violence and job satisfaction and the relationship
      between workplace violence and nurses' turnover intention. CONCLUSIONS: Adverse
      effects of workplace violence were demonstrated in this study. Decreases in job
      satisfaction were a vital mediating factor. The moderating effect of subjective
      well-being was helpful in reducing the harm of workplace violence to nurses and
      in decreasing their turnover intention. RELEVANCE TO CLINICAL PRACTICE: Workplace
      violence and its negative impact on nursing work should not go unnoticed by
      nursing managers. Nurses' subjective well-being is critical in controlling and
      mitigating the adverse effects of workplace violence.

PMID- 29446552
TI  - Nanopore Detection of Single-Molecule Binding within a Metallosupramolecular
      Cage.
AB  - Guest encapsulation is a fundamental property of coordination cages. However,
      there is a paucity of methods capable of quantifying the dynamics of guest
      binding processes. Here, we demonstrate nanopore detection of single-molecule
      binding within metallosupramolecular cages. Real-time monitoring of the ion
      current flowing through a transmembrane alpha-hemolysin nanopore resolved the
      binding of different guests to both cage enantiomers. This enabled the single
      molecule kinetics of guest binding to be quantified, whereas the ordering and
      durations of events were consistent with a guest-exchange mechanism that does not
      involve ligand dissociation. In addition to providing a new approach for single
      molecule interrogation of dynamic supramolecular processes, this work also
      establishes that cage complexes which are too large to enter the nanopore can be
      exploited for detecting small molecules, thus constituting a new class of
      molecular adapter.

PMID- 29446551
TI  - Targeting Murine Mesenchymal Stem Cells to Kidney Injury Molecule-1 Improves
      Their Therapeutic Efficacy in Chronic Ischemic Kidney Injury.
AB  - Mesenchymal stem cells (MSC) have been experimentally used for kidney repair, but
      modest retention limits their efficacy. Cell-surface coating allows modulating
      MSC homing and interaction with target cells. We coated mouse adipose tissue
      derived MSC with antibodies directed against kidney injury molecule-1 (ab-KIM1),
      which is upregulated in injured kidneys, and tested the hypothesis that this
      would enhance their therapeutic effects in ischemic kidney injury. Untreated MSC,
      ab-KIM1-coated MSC (KIM-MSC), or vehicle, were injected systemically into the
      carotid artery of 2-kidneys, 1-clip mice 2 weeks after surgery. MSC retention in
      different organs was explored 24 hours, 48 hours, or 2 weeks after injection.
      Renal volume, perfusion, and oxygenation were studied 2 weeks after injection
      using magnetic resonance imaging in vivo, and renal inflammation, apoptosis,
      capillary density, and fibrosis ex vivo. The ab-KIM1 coating had little effect on
      MSC viability or proliferation. The stenotic kidney showed upregulated KIM1
      expression, selective homing, and greater retention of KIM-MSC compared to
      untreated MSC and compared to other organs. KIM-MSC-injected mice improved renal
      perfusion and capillary density, and attenuated oxidative damage, apoptosis, and
      fibrosis compared to mice treated with vehicle or with native MSC. In conclusion,
      MSC coating with ab-KIM1 increased their retention in the ischemic kidney and
      enhanced their therapeutic efficacy. This novel method may be useful to
      selectively target injured kidneys, and supports further development of
      strategies to enhance cell-based treatment of ischemic kidney injury. Stem Cells
      Translational Medicine 2018;7:394-403.

PMID- 29446553
TI  - Children's moral experiences of crisis management in a child mental health
      setting.
AB  - The experiences of children related to conflict and crisis management in child
      mental health settings, especially those aged 12 and below, have been rarely
      studied. This study examined the moral experiences of children related to
      conflict and crisis management and the related use of restraint and seclusion in
      a child mental health setting. A 5-month focused ethnography using a
      participatory hermeneutic framework was conducted in a day hospital programme for
      children with severe disruptive disorders within a mental health institute.
      Children considered restraints and seclusion could help them feel safe in certain
      instances, for example if another child was being aggressive towards them or in
      exceptional cases to prevent self-injury. However, their own experiences of being
      restrained were predominantly negative, especially if not knowing the reason for
      their use, which they then found unfair. Some of the children emphasized the
      punitive nature of the use of restraints and seclusion, and most children
      disagreed with these practices when used as a punishment. Children's perspectives
      also highlighted the limits of the use of a uniform de-escalation approach by the
      staff to manage crises. Children considered discussing with the staff and
      developing a relationship with them as more helpful in case of a crisis then the
      use of a de-escalation approach or coercive strategies.

PMID- 29446555
TI  - Ge14 Br8 (PEt3 )4 : A Subhalide Cluster of Germanium.
AB  - Heating a metastable solution of GeI Br to room temperature led to the first
      structurally characterized metalloid subhalide cluster Ge14 Br8 (PEt3 )4 (1).
      Furthermore 1 can be seen as the first isolated binary halide cluster on the way
      from GeI Br to elemental germanium, giving insight into the complex reaction
      mechanism of its disproportionation reaction. Quantum chemical calculations
      further indicate that a classical bonding situation is realized within 1 and that
      the last step of the formation of 1 might include the trapping of GeBr2 units.

PMID- 29446554
TI  - Impact of cigarette smoking on the relationship between body mass index and
      insulin: Longitudinal observation from the Bogalusa Heart Study.
AB  - OBJECTIVES: Despite the inverse association between cigarette smoking and body
      mass index (BMI), it is unknown whether the effect of smoking on insulin is
      mediated through decreased BMI. This study aims to examine the temporal
      relationship between BMI and insulin, the impact of smoking on this relationship
      and the mediation effect of BMI on the association between smoking and insulin
      levels. METHODS: The longitudinal cohort consisted of 1121 adults (807 white and
      314 black participants, mean age, 42.0 years at follow-up) for whom BMI and
      fasting insulin were measured twice, with an average follow-up period of 17.1
      years. Cross-lagged panel and mediation analysis models were used to examine the
      temporal relationship between BMI and insulin, and the mediation effect of BMI on
      the smoking-insulin association. RESULTS: Smoking was inversely associated with
      insulin (regression coefficient, -0.073; P = .015 at baseline and -0.121; P <
      .001 at follow-up), adjusting for age, race and gender. After additional
      adjustment for follow-up periods, the cross-lagged path coefficient from BMI to
      insulin (beta, 0.226; P < .001) was significantly greater than that from insulin
      to BMI (beta, -0.029; P = .208), with P < .001 for the difference. The path
      coefficient from BMI to insulin was significantly greater in non-smokers (beta,
      0.273; P < .001) than in smokers (beta, 0.122; P = .046), with P = .013 for the
      difference. The mediation effect of BMI on the smoking-insulin association was
      estimated at 53.4% (P = .030) at baseline and 58.7% (P < .001) at follow-up.
      CONCLUSIONS: These findings suggest that cigarette smoking has a significant
      impact on the one-directional relationship from BMI to insulin. The insulin
      lowering effect of smoking is predominantly mediated through decreased BMI as the
      result of smoking.

PMID- 29446556
TI  - The origins and early elaboration of projectile technology.
AB  - The ability of Homo sapiens to kill prey at a distance is arguably one of the
      catalysts for our current ecological dominance. Many researchers have suggested
      its origins lie in the African Middle Stone Age or the European Middle
      Palaeolithic (~300-30 thousand years ago), but the perishable components of
      armatures rarely preserve. Most research on this subject therefore emphasises
      analysis of armature tip size, shape, and diagnostic impacts or residues. Other
      lines of evidence have included human skeletal anatomy or analyses of the species
      composition of faunal assemblages. Projectile Impact Marks (PIMs) on
      archaeofaunal remains offer an ideal complement to this work, but their potential
      has been restricted mainly to the later Eurasian zooarchaeological record. A
      review of current evidence and approaches shows that systematic PIM research
      could add much to our understanding of early projectile technology, especially in
      Africa.

PMID- 29446557
TI  - European Society for the Study of Human Evolution 2017: old sites, new methods.

PMID- 29446558
TI  - Seventh Annual Meeting of the European Society for the Study of Human Evolution.

PMID- 29446559
TI  - The handaxe reconsidered.
AB  - The Acheulean handaxe is one of the longest-known and longest-surviving artifacts
      of the Palaeolithic and, despite its experimentally tested functionality, is
      often regarded as puzzling. It is unnecessary to invoke a unique-for-mammals
      genetic mechanism to explain the handaxe phenomenon. Instead, we propose that two
      nongenetic processes are sufficient. The first is a set of ergonomic design
      principles linked to the production of sturdy, hand-held cutting tools in the
      context of a knapped-stone technology that lacked hafting. The second is an
      esthetic preference for regular forms with gradual curves and pleasing
      proportions. Neither process is a cultural meme but, operating together in a
      cultural context, they can account for all of the supposedly puzzling time-space
      patterns presented by handaxes.

PMID- 29446560
TI  - Less of a bird's song than a hard rock ensemble.
AB  - Corbey et al. (2016) propose that the Acheulean handaxe was, at least in part,
      under genetic control. An alternative perspective is offered here, focusing on
      the nature of the Acheulean handaxe and the archaeological record, and re
      emphasizing their status as cultural artefacts. This is based on four main
      arguments challenging the proposals of Corbey et al. Firstly, handaxes do not
      have to track environmental variation to be a cultural artefact, given their role
      as a hand-held butchery knife or multi-purpose tool. Secondly, while handaxe
      shapes do cluster around a basic bauplan, there is also significant variability
      in the Acheulean handaxe record, characterized by site-specific modal forms and
      locally expressed, short-lived, idiosyncratic traits. Critically, this
      variability occurs in both time and space, is multi-scalar, and does not appear
      to be under genetic control. Thirdly, handaxes were produced in social contexts,
      within which their makers grew up exposed to the sights and sounds of artefact
      manufacture. Finally, the localized absences of handaxes at different times and
      places in the Lower Paleolithic world is suggestive of active behavioral choices
      and population dynamics rather than genetic controls.

PMID- 29446562
TI  - The 40th meeting of the American Society of Primatologists.

PMID- 29446561
TI  - The role of play objects and object play in human cognitive evolution and
      innovation.
AB  - In this contribution, we address a major puzzle in the evolution of human
      material culture: If maturing individuals just learn their parental generation's
      material culture, then what is the origin of key innovations as documented in the
      archeological record? We approach this question by coupling a life-history model
      of the costs and benefits of experimentation with a niche-construction
      perspective. Niche-construction theory suggests that the behavior of organisms
      and their modification of the world around them have important evolutionary
      ramifications by altering developmental settings and selection pressures. Part of
      Homo sapiens' niche is the active provisioning of children with play objects -
      sometimes functional miniatures of adult tools - and the encouragement of object
      play, such as playful knapping with stones. Our model suggests that salient
      material culture innovation may occur or be primed in a late childhood or
      adolescence sweet spot when cognitive and physical abilities are sufficiently
      mature but before the full onset of the concerns and costs associated with
      reproduction. We evaluate the model against a series of archeological cases and
      make suggestions for future research.

PMID- 29446563
TI  - The Evolution of Evolutionary Anthropology.

PMID- 29446564
TI  - Glycosylation on proteins of the intestine and perimicrovillar membrane of
      Triatoma (Meccus) pallidipennis, under different feeding conditions.
AB  - Trypanosoma cruzi, the causative agent of Chagas disease, interacts with
      molecules in the midgut of its insect vector to multiply and reach the infective
      stage. Many studies suggest that the parasite binds to midgut-specific glycans.
      We identified several glycoproteins expressed in the intestine and
      perimicrovillar membrane (PMM) of Triatoma (Meccus) pallidipennis under different
      feeding conditions. In order to assess changes in protein-linked glycans, we
      performed lectin and immunoblot analyses on glycoprotein extracts from these
      intestinal tissues using well-characterized lectins, and an antibody, which
      collectively recognize a wide range of different glycans epitopes. We observed
      that the amount and composition of proteins and glycoproteins associated with
      different glycans structures changed over time in the intestines and PMM under
      different physiological conditions. PMM extracts contained a wide variety of
      glycoproteins with different sugar residues, including abundant high-mannose and
      complex sialylated glycans. We propose that these molecules could be involved in
      the process of parasite-vector interactions.

PMID- 29446566
TI  - Celebrating milestones and balancing metrics.

PMID- 29446565
TI  - Targeted surgical parathyroidectomy in end-stage renal disease patients and long
      term metabolic control: A single-center experience in the current era.
AB  - BACKGROUND: The long-term results of surgical parathyroidectomy (PTX) in end
      stage renal disease (ESRD) patients are less well known in the modern era of
      newer activated vitamin-D analogs, calcimimetics and intraoperative monitoring of
      parathyroid hormone (PTH). METHODS: We performed a retrospective chart review of
      all ESRD patients undergoing PTX at the University of Mississippi Medical Center
      between January 2005 and August 2011, with follow-up data as available up to 4
      years. All PTXs were performed with intraoperative second-generation PTH
      monitoring and targeted gland size reduction. RESULTS: The cohort (N = 37) was
      relatively young with a mean (+/-SD) age of 48.4 +/- 13.9. 94.6% of the subjects
      were African American and 59.5% female. Preoperatively, 45.9% received cinacalcet
      (CNC) at a mean dose of 63.5 +/- 20.9 mg. The size of the largest removed glands
      measured 1.7 +/- 0.8 cm and almost all (94.6%) glands had hyperplasia on
      histology. The mean length of inpatient stay was 5.5 +/- 2.4 days. Preoperative
      calcium/phosphorus measured 9.6 +/- 1.2/6.6 +/- 1.7 mg/dL with PTH concentrations
      of 1589 +/- 827 pg/mL. Postoperative PTH values measured 145.4 +/- 119.2 pg/mL.
      Preoperative PTH strongly correlated (P < 0.0001) with both alkaline phosphatase
      (ALP) levels (r: 0.596) and the number of inpatient days (r: 0.545), but not with
      CNC administration. Independent predictors for the duration of hospitalization
      were preoperative ALP (beta 0.469; P = 0.001) and age (beta -0.401; P = 0.005)
      (R2 0.45); for postoperative hypocalcemia, age (beta: -0.321; P = 0.006) and
      preoperative PTH (beta: 0.431; P = 0.036) were significant in linear regression
      models with stepwise selection. CONCLUSION: Gland-sparing PTX achieved acceptable
      control of ESRD-associated hyperparathyroidism in most patients from a
      socioeconomically challenged, underserved population of the United States.

PMID- 29446567
TI  - Prognostic value of the index of microcirculatory resistance after percutaneous
      coronary intervention in patients with non-ST-segment elevation acute coronary
      syndrome.
AB  - BACKGROUND: The prognostic value of physiological indices in non-ST-segment
      elevation acute coronary syndrome (NSTE-ACS) patients undergoing percutaneous
      coronary intervention (PCI) is unknown. We investigated the prognostic efficacy
      of physiological indices obtained after PCI in patients with NSTE-ACS. METHODS:
      Eighty-three patients (men: n = 70, age: 63.7 +/- 9.7 years) undergoing PCI for
      NSTE-ACS within 48 hr postadmission were investigated. Fractional flow reserve
      (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance
      (IMR) of the culprit vessels were measured after the completion of PCI. The
      patients were clinically followed up to determine major cardiac adverse events
      (MACE), including death, congestive heart failure requiring hospitalization, and
      remote coronary revascularization. RESULTS: The median FFR, CFR, and IMR values
      were 0.90 (interquartile range [IQR] 0.86-0.95), 2.38 (IQR 1.75-4.17), and 22.9
      (IQR 11.2-31.5), respectively. During a median follow-up of 20.7 months, 19 MACEs
      (22.9%) were documented. No significant difference in baseline patient
      characteristics, except for age, was detected between patients with and without
      MACE. Patients with MACE showed higher IMR and lower CFR than those without (IMR:
      27.2 vs. 16.3; P = 0.001, CFR: 1.82 vs. 2.55; P = 0.04), whereas FFR was not
      significantly different (0.92 vs. 0.89; P = 0.72), irrespective of the MACE
      occurrence. Post-PCI IMR was the only independent predictor of MACE (hazard ratio
      1.033, 95% confidence interval 1.013-1.052, P = 0.001). The MACE-free survival
      was significantly worse in patients with high post-PCI IMR (chi2 7.12; P =
      0.008). CONCLUSION: Post-PCI IMR may help identify patients at high risk for
      subsequent adverse coronary events who require adjunctive therapeutic strategies.

PMID- 29446568
TI  - Making a (cautious) case for expanding reproductive genetic carrier screens:
      Australian researchers report success, and caveats, with a simultaneous panel of
      cystic fibrosis, fragile X syndrome, and spinal muscular atrophy.

PMID- 29446569
TI  - Cover Image, Volume 176A, Number 3, March 2018.
AB  - The cover image, by Kei Tamai et al., is based on the Clinical Report Fetal
      ultrasonographic findings including cerebral hyperechogenicity in a patient with
      non-lethal form of Raine syndrome, DOI: 10.1002/ajmg.a.38598.

PMID- 29446570
TI  - Gratitude, protective buffering, and cognitive dissonance: How families respond
      to pediatric whole exome sequencing in the absence of actionable results.
AB  - Clinical genome and exome sequencing (CGES) may identify variants leading to
      targeted management of existing conditions. Yet, CGES often fails to identify
      pathogenic diagnostic variants and introduces uncertainties by detecting variants
      of uncertain significance (VUS) and secondary findings. This study investigated
      how families understand findings and adjust their perspectives on CGES. As part
      of NIH's Clinical Sequencing Exploratory Research Consortium, children were
      recruited from clinics at the Children's Hospital of Pennsylvania (CHOP) and
      offered exome sequencing. Primary pathogenic and possibly pathogenic, and some
      secondary findings were returned. Investigators digitally recorded results
      disclosure sessions and conducted 3-month follow up interviews with 10
      adolescents and a parent. An interdisciplinary team coded all transcripts.
      Participants were initially disappointed with findings, yet reactions evolved
      within disclosure sessions and at 3-month interviews toward acceptance and
      satisfaction. Families erroneously expected, and prepared extensively, to learn
      about risk for common conditions. During disclosure sessions, parents and
      adolescents varied in how they monitored and responded to each others reactions.
      Several misinterpreted, or overestimated, the utility of findings to attribute
      meaning and achieve closure for the CGES experience. Participants perceived
      testing as an opportunity to improve disease management despite results that did
      not introduce new treatments or diagnoses. Future research may examine whether
      families experience cognitive dissonance regarding discrepancies between
      expectations and findings, and how protective buffering minimizes the burden of
      disappointment on loved ones. As CGES is increasingly integrated into clinical
      care providers must contend with tempering family expectations and
      interpretations of findings while managing complex medical care.

PMID- 29446572
TI  - [The dynamics of the occupational morbidity rate in the Eastern Siberia].
AB  - The dynamics and structure of the occupational morbidity rate in main branches of
      the industry in the Eastern Siberia for the 2000-2015 (on the example of the
      Irkutsk region) is presented in this paper. During the observation period there
      were noted the significant gain in the number of cases of occupational diseases
      registered in such different branches of industry as Coal and Lignite Mining,
      ship and aircraft building, and in some other branches (metallurgical production,
      air transport, pulp production, electric power distribution industry). In the
      structure of the occupational morbidity leading positions are occupied by
      diseases associated with the exposure to physical factors, industrial aerosols,
      physical overload and overexertion of certain organs and systems. The main
      reasons and factors contributing to the gain of the occupational morbidity rate
      are the imperfection of technological processes, working places, personal
      protective equipment and/or their lack, constructive defects of machines and
      equipment, the violation of safety regulations, regimen of the work and rest,
      insufficiently high level of medical and preventive maintenance, delayed making
      of decisions for the rational employment to the workers with the revealed early
      forms of occupational diseases. There pointed out priority directions of the
      prevention the implementation of which will allow to decline the level of the
      occupational morbidity rate. The main directions are the implementation of
      economically caused mechanisms of the interest in the preservation of workers '
      health; implementation of the regional aimed programs; the introduction of new
      processes, equipment and mechanisms meeting modern hygienic requirements; the
      assessment of occupational risk with the creation and implementation of the
      system of monitoring for the dynamics of working conditions and the state of the
      workers ' health for the making corrective management solutions on the
      optimization and elevation of the efficacy and relevance of developed and
      implemented preventive health measures.

PMID- 29446573
TI  - [Modern aspects of the conservation and promotion of health of firefighters].
AB  - On the basis of complex hygienic studies there were determined conditions of the
      work of firefighters in liquidation of foci of fires at the incipient stage,
      identified the complex of toxic substances, their quantitative content in the
      area of the smoke of fires. The analysis of the etiological role of occupational
      factors in the shaping of the morbidity and the physiological and clinical
      manifestations, established indices of the risk for occupational and industrial
      caused pathology have allowed to substantiate the relationship of a number of
      nosological forms associated with working conditions of firefighters. There was
      developed a system of preventive activities for the promotion and preservation of
      the health of firefighters, as well as a conceptual model for monitoring of
      working conditions and state of health.

PMID- 29446574
TI  - [Vibration disease: hygienic and medical aspects].
AB  - The hygienic assessment of working conditions of employees exposed to local
      vibration established that working conditions for employees ofvibration dangerous
      occupations at the aircraft plant according to the degree from a health
      standpoint and hazard are referred to the fourth (dangerous) class of the degree
      of danger that stipulates stable high levels of the morbidity rate. The leading
      factor is a local vibration that results in the consistently high levels of
      occupational morbidity rate. There was shown the efficiency of the use of the
      pulsed magnetic stimulation in the treatment ofpatients with vibration disease
      associated with the exposure to local vibration. For the evaluation of the
      effectiveness of treatment in patients the condition of the central nervous
      system was determined with the use of computer electroencephalography with the
      registration of visual and auditory evoked potentials and somatosensory evoked
      potentials; there was studied the state of the peripheral nerves in arms and legs
      relying upom electromyographic data; there was performed psychological study.
      After the performance of pulse magnetic stimulation in patients diagnosed to have
      the vibration diseases there were observed the improvement in the interaction of
      cortical-subcortical structures and associative areas of the frontal and temporal
      lobes of the brain. After treatment there was noted the shortening of the time of
      the conduction of the afferent wave of the excitation at the level of the
      cervical spinal cord, subcortical structures and the central conduction time.
      There was restored previously reduced the speed of the conduction of the impulse
      via the distal parts of the tibial and median nerve, through the ulnar nerve in
      the area of the elbow joint. There was noted the rise in the average temperature
      on the hands; the decline of thresholds of vibration and pain sensitivity; the
      improvement of indices characterizing of the state of mnestic- attentional and
      psycho-emotional scope of activity.

PMID- 29446575
TI  - [Psychophysiological state of children in conditions of informatization of their
      life activity and intensification of education].
AB  - The transition to a new stage of the development - the information society is an
      objective reality and has an influence on all areas of the activity of the
      society, including the establishment of a child as an object of the hygienic
      research. In conditions of the general informatization of the society, the
      appearance of so-called "clip thinking," explains the maladjustment of
      educational technologies to mechanisms of children ' and teenagers 'perception
      and is confirmed by the growth of the school pathology and the gain in the
      morbidity rate. In the investigation on the example of the educational
      institutions of Irkutsk it was executed the evaluation of the impact of the
      intensification of informatization of education and personal development. For the
      investigation there were formed 2 groups ofpreschools with different levels of
      informatization in the same preschool institution of the central district of the
      city of Irkutsk but in different periods of time. In total there were observed
      211 children aged of 5.5 to 6.5 years. For the study the influence of the
      intensification (and informatization of training there were formed 2 groups of
      small schoolchildren with different levels of intensification (and
      informatization) of education. The total number of cases accountedfor 465
      children aged of 7-9 years. There were suggested methodical approaches to the
      estimation of the health status of the children, with taking into account the
      inevitable influence offactors of informatization and the intensification of
      education. The performed investigations have allowed to reveal the following
      tendencies in the shaping of the psychophysical state of health and development
      of children: an increase of level of informatization of education and personal
      and accomplishment; intensification of learning working; reduction of the
      attention level; imagination and visual divergence; capability to the linear
      differentiation and construction of inferences; fear to fail to meet the
      expectations of surrounding people and low resistance to stress; the increase
      speed of data processing along with fall in quality; the gain in hyperactivity.

PMID- 29446576
TI  - [Ambient air pollution of territories of children preschool institutions by
      emissions of vehicle components and health of children population].
AB  - The aim of this study was the assessment of levels of pollution of territories of
      preschool educational institutions (PEI) by components of vehicle emissions, in
      dependence on their locations relatively to highways with different traffic load
      and, in this regard, the assessment of children health according to the incidence
      on the seeking medical advice. To achieve this goal there were solved following
      tasks: to assess air pollution levels of PEI territories by components of vehicle
      emissions; to evaluate levels and the structure of morbidity rate according to
      seeking medical advice by children attending observed PEI. In the article there
      is presented the evaluation of air pollution levels of the components of vehicle
      emissions territories 4 PEI of the city of Irkutsk located near to highways with
      different intensity the road transport load. The research results were obtained
      with the use of "Methodics for the determination vehicle emissions for summary
      calculations of ambient air pollution in cities", which allows to determine the
      maximum emissions of a moving vehicle per time unit (g/s) for the main combustion
      components and with following use of software "Superhighway -city" to calculate
      surface concentrations of considered pollutants in the surface ambient air layer
      (1 m) in MPC proportions. The highest levels of contamination on the content of
      nitric oxide and benzo- (a)-pyrene (4 and 6,5 MPC respectively) are registered in
      the territories adjacent to the PEI motorways with high load tracking. To assess
      the morbidity rate according to seeking medical advice by children attending PEI
      with different road transport load there were used records from outpatient
      medical cards "Medical card of the child" (f.112/y). Morbidity rate according to
      seeking medical advice was evaluated in dynamics throughout five years and
      calculated per 1000 cases. The total sample size accounted for 670 children. The
      highest morbidity incidence rate levels according both to seeking medical advice
      and the class of respiratory diseases were recorded in PEI located in close
      proximity to the highway with a high load of vehicle transport.

PMID- 29446577
TI  - [Hygienic assessment of intraschool environment in rural and urban secondary
      school institutions].
AB  - The purpose of the research is to assess the intra-environment indices in urban
      and rural secondary schools. In the course of special studies there was given the
      hygienic assessment of the climate, illumination and air quality of classrooms.
      In classrooms in rural schools microclimate indices were established to fail to
      meet hygienic requirements mainly on the temperature and humidity parameters. In
      rural schools, the temperature was decreased to 16-17  degrees C in 19.0 +/- 8.6%
      of classrooms, humidity was elevated to 63.1% in 25.7 +/- 7.4% of classrooms.
      Among urban schools the humidity in 49.6 +/- 4.4% of classrooms reduced to 23.3
      +/- 0.3%, in 20.8 +/- 5.4% of offices it was increased to 71.9 +/- 0.9%. The
      coefficient of the natural illumination in rural schools has been reduced to 0.86
      1.4% in 33.9 +/- 14.2% of classrooms. In 25.1 +/- 2.3% of classrooms in urban
      schools the level of natural light ratio was below the normative values and
      varied in the range of 0.32-1.3%. It is noted that in the offices of informatics
      natural light indices are significantly lower than in the classrooms for core
      subjects. The artificial lighting in urban schools was found to be lower than
      hygienic standards on the desks by 1.9 times, 2.2 times - at the board. There
      were obtained statistically significant handshaking health problems of urban
      schoolchildren due to intraenvironmental factors. The c dimate in surveyed gyms
      in rural schools is different in the low temperature and high humidity. The
      hygienic assessment of the air pollution classrooms' medium was executed for a
      range of chemicals: formaldehyde, carbon monoxide, nitrogen dioxide, sulfur
      dioxide, particulate matter. Concentrations of formaldehyde; nitrogen dioxide,
      suspended solids in the air in classrooms in urban schools appeared to be higher
      than in rural schools. Carbon monoxide concentrations in classrooms in rural
      schools was found to exceed their values in urban schools. The air in classrooms
      of the one of the cities was found to be differed by a specific atmosphere for
      its chemical - hydrogen fluoride, in concentrations exceeding the maximum allowed
      concentration by 3-3.5 times.

PMID- 29446578
TI  - [Characteristics of physical growth of schoolchildren in Mongolia and their
      forming factors].
AB  - The article considers the findings of hygienic assessments of educational
      conditions in urban and rural schools in Mongolia and socio-economic conditions
      of living of schoolchildren and analysis of anthropometric measurements of
      schoolchildren aged of 7-16 years in relation to the assessment of harmonicity of
      their physical development. Hygienic conditions in Mongolian schools are
      characterized by improper organization of the educational - accomplishment
      process, high occupancy rate in classes causing insufficient space for a pupil
      and disconformity of school furniture parameters of school desks and chairs to
      growth and age requirements of pupils. Comparative assessment of socio-economic
      factors revealed (videleno avtorom) that the majority (84.1%) of rural pupils
      reside in uncomfortable houses and gerdwellings, 58.5 % - in large families with
      many children, 46.3 % - in families with poor living conditions. There were
      obtained data about differences in physical development of urban and rural
      schoolchildren pronounced with age by the gain in the number of children with
      disharmonious development and children with lower physical indices of the
      development, delayed by 1-2 years appearance of the crossing of growth and growth
      shift typical for rural children in comparison with their urban counterparts.
      According to results of multivariate regression analysis most significant factors
      for the formation of physical development of school children in descending order
      are academic workload, the place of residence, the number of children in the
      family, uncomfortable living conditions, household income and parent's education.
      In the presence of these factors, the risk of the formation of disharmonious
      physical growth of school children increases by 1.8-2.8 times. The probability of
      the risk offormation of disharmonious physical development of schoolchildren
      living in rural areas was found to be by 2.5 times more than for their urban
      counterparts. The results can be usedfor scientific substantiation and
      development of targeted health measures.

PMID- 29446579
TI  - [Thyroid gland pathology in children population exposed to the combination of
      iodine deficiency and fluoride pollution of environment].
AB  - The article presents results of study of the impact of iodine deficiency and
      technogenic fluoride on the state of the thyroid gland in children. On the
      example of two districts of the city of Bratsk there were executed dynamic
      investigations (2002 and 2012), including the estimation of the pollution of
      ambient air and soil by fluorine compounds, levels of iodine intake by the body,
      the clinical examination of children aged from 5 to 7 years d and interviewing of
      their parents. In the course of the medical examination there were executed:
      physical examination by the pediatrician, endocrinologist, ultrasound examination
      of the thyroid gland, the determination both of serum hormone content by
      radioimmunoassay and urinary excretion offluorine and iodine. Concentrations of
      hydrogen fluoride and a solidfluorides in ambient air led to the accumulation
      offluoride ion in the soil. The iodine entering with drinking water and food, was
      established to provide only 37.5-50% of the daily requirement of iodine.
      Increased fluoride ion content in urine and milk teeth in children is associated
      with the concentrations of the fluorine-containing pollutants in the ambient air
      and soil. The fluoride pollution against the background of the natural iodine
      deficiency was established to increase the frequency of functional and
      morphological disorders of the thyroid gland in children.

PMID- 29446581
TI  - Odontogenic focal infection is a possible trigger of severe Henoch-Schonlein
      purpura nephritis.

PMID- 29446580
TI  - Is there any difference between the symptomatology and clinical findings of viral
      agents causing dehydration?
AB  - BACKGROUND: Acute gastroenteritis is responsible for dehydration in many
      children. The viruses like rotavirus, norovirus, and adenovirus are considered
      the main causative agents of gastroenteritis. The goal of this study is the
      evaluation of the symptoms, clinical findings and hospitalization requirements in
      pediatric patients with dehydration secondary to viral gastroenteritis. METHODS:
      The distribution of age, symptoms, clinical and laboratory findings and
      hospitalization requirements of 156 viral acute gastroenteritis patients with
      moderate dehydration were evaluated retrospectively. Patients were between 3
      months to 16 years of age (mean: 38.7 months). The patients were categorized into
      four groups according to etiological agents as rotavirus, norovirus, adenovirus,
      and mixed infections for the comparison of symptoms, clinical characteristics,
      laboratory results, seasonal distribution, treatment requirements,
      hospitalization unit, and hospitalization period. Age groups were categorized as
      0-24 months, 25-72 months, and >72 months. Clinical characteristics of patients
      were analyzed for hospitalization period as <24 hours, and >=24 hours. RESULTS:
      Moderate-degree dehydration was detected in 156 patients with acute
      gastroenteritis (156/278) caused by rotavirus (60.5%), norovirus (58%) and
      adenovirus (42%) respectively. The common symptoms of all patients were vomiting,
      diarrhea, abdominal pain and malaise, although fever was seen mostly in the
      patients of rotavirus. Aspartat aminotransferase (AST) was elevated in rotavirus
      gastroenteritis (11.5%) more than norovirus (5.4%) and adenovirus (0.8%)
      infections. Elevated blood urea nitrogen (BUN) levels (>20 mg/dL) were shown in
      79.3%, of patients especially in rotavirus (43.8%). CONCLUSIONS: The main agents
      of acute gastroenteritis which caused dehydration were norovirus and rotavirus in
      our patients. Rotavirus was detected in most of the hospitalized patients with
      severe symptoms. AST was prominently elevated in rotavirus gastroenteritis. The
      clinical characteristics and some laboratory findings including hyperglycemia,
      leukocytosis, and elevated AST may be helpful in differentiating rotavirus from
      norovirus gastroenteritis. BUN level was insignificantly elevated in patients
      with rotavirus.

PMID- 29446582
TI  - What is hindering research on psychological aspects of fathers of premature
      infants?

PMID- 29446583
TI  - [Determination of priority unfavorable environmental factors].
AB  - In the Irkutsk region there are recorded high indices of rates of morbidity,
      disability, mortality rate of the working-age population and low levels of life
      expectancy of the population, that is confirmed by ranking position levels among
      the all subjects of the Russian Federation. According to all mentioned indices of
      health the region is inside the top ten unfavorable regions of Russia. In
      relation to the problem in the state of health of the adult population the
      estimation of the causal relationships between environmental factors and certain
      health indices is actual. The list of studiedfactors included health indices that
      characterize the harmful working conditions of the working population and basic
      socioeconomic indices in the region. Estimation of causal-relationship
      relationships was performed with the use of methods of multivariate analysis -
      correlation and multiple linear regression. In the selection offactors for the
      construction of mathematical models of multiple regression there were used
      methods of the analysis of variables variability, pair correlation coefficients
      matrix and sequential switching covariates to eliminate the problems of
      multicollinearity, pre-standardization of indices for the elevation of the
      numerical stability of regression analysis algorithm. As a result of the
      execution of the analysis there were constructed statistical models for the
      dependence in the system variables "environment - public health", which allowed
      to identify the most informative regression models for the adult population
      health according to indices of primary disability of the population, the
      mortality rate and life expectancy of the working age population. According to
      results of the analysis there were identified priority factors affecting on the
      health of the adult population of the Irkutsk region. To these factors there are
      referred the proportion of workplaces failing to meet sanitary standards for
      vibration and 8 socio-economic indices of living standards of the population.

PMID- 29446584
TI  - [Induction of apoptosis in neurons of white rats under exposure of
      nanobiocomposite based on ag (0) nanoparticles and arabinogalactan].
AB  - There are presented results of the immunohistochemical study of neural tissue of
      outbred albino rats exposed for 9 days to the influence of the silver
      nanobiocomposite consisted of silver nanoparticles encapsulated into a matrix of
      a natural polymer - arabinogalactan. The research of albino rats was performed in
      2 stages: half of the rats in each groups were decapitated immediately after the
      exposure (early period) and the rest animals - 6 months after the end of exposure
      (remote period). The impact of the studied substance was proved to cause
      functional changes in cells of the nervous tissue. After the subacute
      administration of the nanobiocomposite - argentum-arabinogalactan (nano-Ag-AG) in
      cells of the nervous tissue of the brain of albino rats the expression of
      apoptotic and anti-apoptotic protein (caspase-3 and bcl-2) was established to be
      changed. The number of normal neurons producing protein caspase-3 sharply
      increases. Herewith the number of immunonegative neurons fairly declines. Along
      with this there is noted the high level of bcl-2 content, one function ofwhich is
      the preclusion ofapoptosis. In preparations there is revealed a significant gain
      in the number of bcl-2 expressing neurons, however, the protective effect of the
      protein is not fully realized, that leads to the significantly increase in the
      content of damaged hyperchromatic cells. The evaluation of results of the
      immunohistochemical study of the nervous tissue of albino rats according to data
      concerning the proteins caspase-3 and bcl-2 expression permits to make a
      conclusion about the capability of nanoargentum encapsulated into polymer matrix
      by passing the blood-brain barrier to induce the triggering apoptosis cascade in
      neurons of the cerebral cortex.

PMID- 29446585
TI  - [Assessment of nutrition of students of educational institutions of the various
      type].
AB  - Among the risk factors that have priority in shaping the health of the
      population, a leading place is held by a rational nutrition. Presented results
      indicate to the absence of a stable group eating regularly, with the rational
      regularity and having all the necessary meals and the recommended food set. In
      the population of the adult people of the city of Irkutsk there is revealed the
      role of the nutritional factor in the formation of morbidity rate level of the
      adult population. It was found that the risk of diseases of the circulatory
      system accounted of 2.5 (95% CI: 2.1-3.6), for infectious and parasitic diseases 
      2.4 (95% CI: 1.7-3.5), for the endocrine system - 2.2 (95% CI: 1.4-3.4), andfor
      the urinary system - 2.3 (95% CI: 1,7-3,0).

PMID- 29446586
TI  - [Cognitive brain-Computer interface and probable aspects of its practical
      application].
AB  - A new type of brain-computer interface was elaborated. It considers a variety of
      brain activity parameters to determine the type of mental operation being
      performed at the moment. The corresponding algorithm previously developed in the
      lab was modified for real-time application. The possibility of interface
      application for cognitive skills training was investigated. In the proposed
      paradigm, as soon as the EEG spectral pattern was adequate for the current task,
      some clue to the solution was presented. As we supposed, such positive
      biofeedback should facilitate memorization of the current brain state. After just
      one learning session, the differences in EEG spectra, corresponding two types of
      tasks, were concentrated in more narrow frequency ranges. It indicates the
      decrease of mental effort. Moreover, the majority of subjects succeeded to solve
      the tasks faster, that's an evidence of efficiency increased. The developed
      interface could be used for the new type of training, based on objective features
      of brain activity.

PMID- 29446587
TI  - [Sources of electrophysiological and foci of hemodynamic brain activity most
      relevant for controlling a hybrid brain-Computer interface based on
      classification of EEG patterns and near-infrared spectrography signals during
      motor imagery].
AB  - The method is described for joint use of electroencephalography and near-infrared
      spectrography for location of sources of electrophysiological and focuses of
      hemodynamic brain activity during motor execution and imagination. The sources of
      electrophysiological and focuses of hemodynamic activity the most relevant for
      controlling the hybrid brain-computer interface based on motor imagery are
      revealed and discussed.

PMID- 29446588
TI  - [Hygiene and the spectral energtic light pattern].
AB  - There are considered methodological bases of multicriteria synthesis of a
      spectral energetic pattern for the evaluation of the excessive share of blue and
      red light in the spectrum of artificial energy sources. The basis of this
      methodology is relied upon on the hygienic approach to the spectrum analysis of
      solar and led light. Relying upon on "photobiological paradox of vision"
      according to M. A. Ostrovsky, conditions of "melanopsin cross" and mechanisms of
      adverse impact of light on vision, all the spectral-energy characteristics of
      solar light were divided into subspaces. The border between them became a
      spectral energy pattern for the evaluation of artificial sources on the security
      of their impact on eye and human health according to criteria of the excessive
      dose of blue or red light. On two examples there was shown the effectiveness and
      clarity of this estimation with the using of the spectral energetic pattern of
      light.

PMID- 29446589
TI  - [The approach to the regulation of mercury according to the content of its
      termoforms in soils and bed loads].
AB  - The article contains the results of the ecological and hygienic diagnostics of
      conditions of lands of areas of different sizes and varying degrees of
      urbanization, located in different agro-climatic conditions of European Russia
      (the southern Astrakhan region, he city of Moscow). Assessments of the state of
      territories use a new approach to rationing of Hg according to quantitative
      ratios of the content of its thermoforms in soils, grounds and alluvium (in litho
      substrate). The method of diagnostics is based on known properties of Hg forms:
      their geochemical activity (migration mobility) and toxicity decline along with
      the increment of the Hg temperature threshold of the release in the process of
      continuous warming up of the litho substrate sample (up to 1100 degrees C).
      Thermoforms are not tied to specific minerals or chemicals and are conditionally
      designated as FR (Free: <180 degrees C), CL (Chloride: 180-250 degrees C), FS and
      CS (physically and chemically sorbed: 250-400 degrees C), SU (Sulfide: 400-500
      degrees C) IS (isomorphic: >500 degrees C) Hg forms. Among forms, also
      conditionally according to complexes of low, medium and high temperature
      variations(FR + CL, FS + CS and SU + IZ, respectively, there are selected groups
      of "mobile", "sustainable" and "inert" forms. For technogenic Hg there is
      characterized the predominance in the sample of "mobile" and to lesser extent
      degree - "stable" thermoforms. The more intensive this predominance is, the
      higher is environmental hazard. The natural accumulation is diagnosed by the
      presence and prevalence of the sum of moderate - and high-temperature inert forms
      of Hg. According to the ratios of Hg content, its forms and groups, as well as
      the density of correlationships between them, 6 indices of the conditions of
      soils and alluvium were developed by ourselves.Main coefficients out of indices
      on informativeness of results of diagnostics are the following factors:
      Endogenous input, Geochemical activity and Hg mobility. With regard to the
      combination of variability in indices, the total amount of Hg, the genesis and
      intensity of its accumulation (natural or anthropogenic), there were also
      developed ranking scales of the ecological and hygienic condition of the land
      areas and surface water bodies. As a result, on the base of such approach to the
      regulation of Hg the information value of assessments of mercury contamination of
      land significantly increased. At the objects of assessments there were identified
      following areas: foci of the manifestation of Hg hypolimnetic emanations on the
      landscape surface - dispersion halos in the areas of the Earth crust fracture
      (the dome of the Astrakhan gas condensate field); environmentally dangerous
      (sometimes even at a low total content of Hg) parts of cities, towns, their
      districts, as well as beds of watercourses and water reservoirs bottom (the Volga
      river valley and delta, the Lefortovo quarter in Moscow). There was also
      diagnosed the threshold of the background distribution of gross Hg content
      detected = 0.2-0.3 mg/kg. Its magnitude is consistent with domestic and abroad
      safe levels of Hg accumulation in soils = 0.3-0.4 mg/kg. The approach provides
      the differentiation of the environmental hazard lands. Technology of the approach
      can be used in the development of normative Document for the diagnosis of
      environmental and sanitary condition of territories in the system of
      Classifications of hazard of waste, in decontamination of territories, water
      areas and land zoning according to the criteria of natural or anthropogenic Hg
      accumulation.

PMID- 29446590
TI  - [Biochemical protective mechanisms in the accumulation of heavy metals in
      organisms].
AB  - At present due to the environmental contamination by heavy metals there is a
      great interest to investigate the processes of their both accumulation in plants
      and toxic effect on biochemical indices. Therefore the objective of this research
      was the analysis of the alteration of the system of antioxidant protection
      ofplants in conditions of soil contamination by copper and zinc. Research object
      were germinants of oat in amount of300 plants in each variant of the experiment.
      For the performance of the experiment, the sand was equally contaminated by
      sulfates of Cu and Zn in concentration of 2 MPC on its gross content in soil. The
      experiment lastedfor 2 weeks. For the implementation of the objective of research
      there was analyzed the contentof both Cu and Zn in plants exposed to soil
      contamination. Additionally there was performed an analysis of as the content of
      lipids peroxidation products, phenols and flavonoids; as well the activity
      ofperoxidase, catalase and photosynthetic system. Under the soil contamination by
      copper and zinc corresponding to 2 MPC the accumulation of heavy metals was
      established to be happening in plants. If compared copper accumulation was higher
      than zinc accumulation that can be explained by the high migration capability of
      zinc. Under combined impact of two metals there was revealed their antagonistic
      interaction. There was established an elevated content of lipids peroxidation
      products in cells as a sequence of the accumulation of heavy metals in plants. As
      a result of the elevation of the content of lipids peroxidation products there
      was revealed a raised activity ofphotosynthetic apparatus and antioxidant system
      (carotenoids, catalase and peroxidase) in the cell. The decrease of the content
      ofphenols and flavonoids is related with the usage of this system of antioxidant
      protection for the neutralization of lipids peroxidation processes.

PMID- 29446591
TI  - [Impact of waste landfills in the Saratov region on the sanitary condition of the
      soil].
AB  - Monitoring of environment in regions of the location of waste landfills includes
      the implementation of the control over a sanitary condition of soils. The main
      origins of the spread ofpollutants into soils are the solid particles from
      aerosol emissions from the functioning of landfills transmitted to surrounding
      territories. Within zones of the impact of three largest waste landfills in the
      Saratov region (Aleksandrovsky, Guselsky in the city of Saratov and Balakovsky in
      the city of Balakovo) there were taken 152 soil samples. According to results of
      the estimation in soil concentration of gross and motile forms of heavy metals of
      the first (Zn, Cd, Ni) and the second danger classes (Cu, Cr, Pb) there was
      performed the analysis of coefficients of danger- K0 and total coefficients
      ofpollution - Zc. There was executed the assessment of both a sanitary and
      hygienic condition of soils and degree of danger ofpollution. The most contrast
      areal features of the distribution of the danger coefficient - Ko in soils are
      characteristic for motile forms of heavy metals. For all three studied objects
      persistently there is stood out the dangerous and areal pollution of soils by
      association of Ni and Cu . The danger ofpollution of soils by gross forms of
      heavy metals is minimum. The coefficient of total pollution of Zc exceeds
      admissible level on motile forms of heavy metals only for the soils surrounding
      the Balakovo landfill. In zones of the impact of waste landfills there are
      located the processed lands with an adverse sanitary and hygienic condition of
      soils. In the region of the Guselsky object soils of the processed agricultural
      grounds are dangerously polluted by motile forms of Ni and Cu. In vicinities of
      the Balakovo waste landfill considerable areas of private gardening enterprises
      are dangerously polluted by the motile forms of Ni, Cu and Zn.

PMID- 29446592
TI  - [Hygienic environmental assessment in the oil-and-gas bearing area on the base of
      cytogenetical and molecular-genetic methods].
AB  - The study have been conducted in settlements located near oilfields of the
      Nizhnevartovsk area, the Khanty-Mansi autonomous district (Russian Federation).
      There were examined 802 persons aged of from 18 to 56 years not proximately
      employed in processes of the oil extraction. Control group was consisted of329
      residents of the north of Tomsk Region living in the area without any polluting
      environment industry. By using such methods of analysis as micronucleus test in
      human buccal cells, the xenobiotic biotransformation of both GSTM1 and GSTT1 gene
      polymorphism, as well as the assessment of oil contamination of local drinking
      water there was executed the hygienic assessment of ecology in the settlements
      located near oil fields. The elevated rate of cytogenetic disorders was
      established to be observed most of all in the residents of this region, as well
      as in persons recently moved to this area. Most significant deviations from the
      control according to the micronucleus test were detected in individuals with the
      GSTM1 (0) /GSTT1(0) genotype. In the control group no such consistent pattern was
      seen.

PMID- 29446593
TI  - [Distribution of bacterial spores in supermarkets].
AB  - This work presents results of the study on the environment prevalence of spores
      of aerobic bacteria, which are of potential danger to human health. The
      investigation of swabs from handles of supermarket trolleys revealed on their
      surface the presence of a large number of spores of unrelated pathogenic bacteria
      carrying as antibiotic resistance genes and the origin of genes protected by
      bacterial spores from harmful environmental conditions as well. The high
      resistance of bacterial spores to antiseptics and disinfectants can be considered
      as the reason for the their accumulation in the environment.

PMID- 29446594
TI  - [Disinfectant compositions on the basis of SAS - Vilagin - water systems].
AB  - The solubility in the SAS - Vilagin - water systems has been investigated at 25 
      degrees S for the purpose of the delivery of liquid disinfectants for various
      surfaces. There are established SAS as effective homogenisers for the stratified
      system "Vilagin - water", not effecting on the bactericidal activity of Vilagin.
      With the aid of the software Optimum there were elaborated compositions in the
      system "Vilagin - Perlastan AL-30-water" which seem to be optimal on both the
      content and disinfectant activity (a degree of disinfecting of 99.99%) mixtures
      in the were developed with the help of computer program Optimum. The pattern of
      the concentrate is presented as: Perlastan AL-30 - 89.1-95.0; Vilagin - 5-10.9;
      water - 0-1.6(mas.%). The efficacy of dermal antiseptics - detergents
      (disinfecting efficiency not less than 60%). Developed gel-like compositions are
      effective in small concentrations in short terms, possess low toxicity,
      multifunctionality, good solubility in water, a long period of storage of
      concentrates.

PMID- 29446595
TI  - [Evaluation of the functional state of the thyroid gland in women residing in the
      ecologically unfavorable Aral Sea region].
AB  - There was executed the clinical examination of 225 women of reproductive age, and
      in all cases there was made blood sampling for the determination of the serum
      level of TSH, free T. Observed cases were divided into three groups: 18-29 years,
      30-39 years, 40-49 years. As a result, a high prevalence of declined thyroid
      function was found to be in the form of subclinical manifested hypothyroidism,
      which exceeds by several times the average incidence of these pathologies in the
      population. It should be noted that the maximum number of women suffering from
      subclinical (21.33% of observed cases), and the manifested hypothyroidism (9.33%
      of the study) was seen in a group of women aged of 18-29 years.

PMID- 29446596
TI  - [Air pollution by particulate matter as the risk factor for the cardiovascular
      diseases].
AB  - In the review there highlighted contemporary concepts about the relation between
      the air pollution by the particulate matter (PM) and human morbidity and
      mortality rate due to cardiovascular diseases. There are considered results of
      the short- and long-term PM impact on the human cardiovascular system in the
      dependence on size, origin, chemical composition, and concentration in the air.
      Authors performed the formalized description of the action and possible effects
      of PM on vascular endothelium presented as an example of systemization.
      Summarizing data respective knowledge collected in the literature were used in
      the article as an example.

PMID- 29446597
TI  - [Complex technology for water and wastewater disinfection and its industrial
      realization in prototype unit].
AB  - Usage of complex automated electrolysis unit for drinking water disinfection and
      wastewater oxidation and coagulation is scoped, its ecological and energy
      efficiency is shown. Properties of technological process of anolyte production
      using membrane electrolysis of brine for water disinfection in municipal
      pipelines and potassium ferrate production using electrochemical dissolution of
      iron anode in NaOH solution for usage in purification plants are listed.
      Construction of modules of industrial prototype for anolyte and ferrate
      production and applied aspects of automation of complex electrolysis unit are
      proved. Results of approbation of electrolytic potassium ferrate for drinking
      water disinfection and wastewater, rain water and environmental water oxidation
      and coagulation are shown.

PMID- 29446598
TI  - [Evaluation of changes in the cortical gait control in post-stroke patients
      induced by the use of the "Regent" soft exoskeleton complex (SEC) by navigated
      transcranial magnetic stimulation].
AB  - The mechanisms underlying the locomotion recovery in poststroke patients remain
      unknown. Navigated transcranial magnetic stimulation (nTMS) is a new method to
      evaluate the functional state of the motor system. Using of the exoskeleton
      complex (EC) allow to correct walking pattern significantly. The aim of this
      study was to evaluate the capability of nTMS to assess changes in gait cortical
      control using EC in poststroke patients. 14 patients suffered subcortical stroke,
      mean age was 53.0 years [49, 62], mean duration of a stroke of 14.2 [7.0; 23.0]
      months were included.  All patients trained with EC for 10 times and also
      received standardized physical therapy.  All patients underwent nTMS, as well as
      clinical assessment using a Fugl-Meyer Scale lower extremity section and 10 m
      walking test before and after trains. A significant decrease of time to walk 10
      meter was observed, while Fugl-Meyer Score remained unchanged.  Patients showed
      the significant reduction of the average latency of motor responses from the
      affected hemisphere and different patterns of size and localization changes in
      both legs' cortical motor areas. Navigates TMS may demonstrate individual
      patterns of changes in cortical representation of leg muscles in post-stroke
      patients with damage of various motor system elements, while using exoskeleton
      complex.  Thus, navigated TMS may be used not only for verification of
      neuroplasticity process, but it may also provide its detailed description.

PMID- 29446599
TI  - [Ecological-hygienic evaluation of the environment of territories being adjacent
      to decultivated uranium mines].
AB  - On the territory of Kazakhstan there are uranium deposits, many ofwhich are in
      mothballed since times of perestroika. Often, the mines are flooded and represent
      a "time-delay bomb". Inside of mines various there are accumulated gases of both
      organic and inorganic nature, periodically thrown out and adversely affecting on
      the health of local populations. The aim of the study was the investigation of
      the state of the environment of Esilsky district of the Akmola region by common
      pollutants and chemicals. As the basic variable for the investigation of ambient
      air there was accepted the maximum one-time concentration of suspended
      substances, phenol, nitrogen dioxide, sulfur dioxide. The results were evaluated
      in relation to the MPC for the analyzed substance in the air according to maximal
      single MPC (MPCms) and daily average MPC (MPCda). The content of metals in the
      water was determined with the use of spectrophotometer PD-303S. Evaluation of the
      results was executed in relation of the MPC of substances in water, by means of
      the comparison with the requirements of Federal standards for drinking water,
      samples from drinking water sources. There were executed calculations of the
      overall index of water pollution (IWVgen), the index of water pollution by heavy
      metals (IWVhm). Chemical analysis of soil was carried out with the use of
      spectrophotometer PD- 303S (Japan), the photometer expert-003 "Ekoniks".
      Evaluation of the results was carried out with the respect to the MPC in the
      soil, the toxicity of all components. Summarizing soil pollution index was
      evaluated for metals contained in the soil at the level of more than or equal to
      1 MAC. The settlement Krasnogorskiy and the village of Kalachi were found to be
      characterized by a low level of air pollution, increased rigidity of drinking
      water exceeded the maximum permissible concentrations of copper by 3.45 times and
      chloride by 1.17 times in the soil cover.

PMID- 29446600
TI  - [Analysis and discussion of seasonal dynamics of indices of chemical composition
      of water from some reservoirs of Uzbekistan].
AB  - The aim of the study was a comparative description and assessment of seasonal
      dynamics of organoleptic characteristics, degree of salinity and chemical
      composition of the water from some reservoirs in Uzbekistan. Organoleptic indices
      and parameters of salinity of water from Kattakurgansky reservoir in the spring
      and summer were established to be practically within the range of MPC. Indices of
      chemical composition of water of the Kattakurgan reservoir were below the upper
      limit of MPC. In water samples of Tuyamuyunsky reservoir organoleptic indices and
      parameters of water salinity in summer were higher than the MPC. Indices of the
      chemical composition of water in the summer time were below upper limits of the
      permissible level, there were noted reliable inter-seasonal differences on the
      content of chlorides and sulfates. Organoleptic indices and the degree of
      mineralization of water samples of Charvaksky reservoir were within the range of
      MPC. All parameters of the chemical composition of water of Charvaksky reservoir
      were lower than the upper MPC limit, regardless of the place of sampling and the
      time of year.

PMID- 29446601
TI  - [Major risk factors and cardiovascular disease prevalence among petrochemical
      workers].
AB  - Objective. Based on the assessment of occupational and non-occupational risk
      factors, development of preventive measures for the reducing of cardiovascular
      diseases (CVD) prevalence among petrochemical workers. Material and Methods. A
      total of 2,634 petrochemical workers have been examined. To identify modified and
      unmodified risk factors for cardiovascular diseases, comprehensive hygienic and
      clinical laboratory studies have been carried out. Results. The obtained results
      have shown a higher riskfor the development of cardiovascular disease among
      operators as compared to metal workers for instrumentation and automation
      repairs. Based on the assessment of risk factors, preventive measures implemented
      at personal and corporative levels have been developed.

PMID- 29446602
TI  - [Hygienic standardization of 2-formylphenoxyethane acid in the air of the working
      zone].
AB  - The toxic properties of 2-formylphenoxyethane acid for hygienic standardization
      in the air of working zone were studied. The substance in the dose equal of DL
      introduced into the stomach for male rats, male and female mice accounted for
      5354, 3698 and 4322 mg/kg. It refers to moderately hazardous substances. No
      significant differences in species and gender sensitivity of animals to the
      substance were noted. It possesses a strong ability to cumulation: C is 2.9. It
      has a marked irritating effect to the mucous membranes of eyes and the moderate
      one - to the skin. Ithas a toxic effect on the liver, kidneys, central nervous
      system. The threshold of acute inhalation effect (Lim) is 120.3 mg/m. At Lim
      level it has no irritating effect on the respiratory tract. The tentative safe
      exposure level of 2-formylphenoxyethane acid in the air of working zone is 1
      mg/m.

PMID- 29446603
TI  - [Hygienic principles of the design of the space and architectural environment of
      kindergartens].
AB  - In the article there are considered current requirements for the design of the
      architectural environment of preschool institutions. These requirements provide
      conditions ofpreservation and promotion of health ofpreschool children. Among
      them are: the association of rooms according to a functional purpose; division of
      children collectives according to the age; rational placement of main rooms for
      the prevention ofpenetration of noise and pollution; ensuring
      convenientfunctional connections between different premises and group rooms and
      the parcel ofpreschool institutions; optimal solution of the light mode; rational
      air and thermal mode. There are made proposals for the expansion of the list of
      hygienic principles of the design of buildings of kindergartens: provision of
      conditions for realization of physical activity of children, the safe use of
      electronic educational equipment, and the creation of the barrier-free
      environment. There was established the insufficiency of areas of group rooms for
      the realization of voluntary motor activity of children in modern kindergartens
      and the need of the revision of the standard of the area of the group room per
      one child.

PMID- 29446604
TI  - [Peculirities of physical development and state of the cardiovascular system in
      young males from various districts of Northeast of Russia].
AB  - The comparative research was carried to study basic indices of physical
      development and cardiovascular system in Aboriginals and north-born Europeans of
      different areas of Russia's northeast (Chukotsky Autonomous District, Magadan
      Region). According to most examined morphofunctional characteristics no
      significant differences were found between the groups of subjects that testify to
      the formation, under the current social conditions, of convergent adaptation
      processes typical for the two ethnic cohorts from the observed areas of residing.
      High percentage of asthenia in body constitution of young residents from Magadan
      Region was common and mostly demonstrated by Aboriginals of the Magadan city.

PMID- 29446605
TI  - [Hygienic estimation of functional reserves and adaptive capabilities of
      students].
AB  - In the article there are presented data on characteristics ofpeculiarities of the
      functional state of medical 1-6 years students of higher educational
      institutions. The results were obtained with the aid of variation pulsometry.
      Students were shown to have typical elevated tone of the sympathetic nervous
      system, especially for students of the 1, 3, 5 and 6 courses, that is confirmed
      by the amplitude mode (AMo), characterizing the sympathetic activity of
      autonomous nervous system (ANS), which is an average of the students 1 year
      accounted for 38.6 +/- 1.89%, for students of the 3 course - 38.5 +/- 1.72%, for
      students of the 5 year (40.9 +/- 3.25 %) and the students of 6 course (46.7 +/-
      2.59%). There was determined the trend to the centralization of the heart rate
      control, as evidenced by a reduced proportion of high-frequency waves (HF) by
      29.2% to 35.2%, exceeding by 3.6 to 14.4 times in waves of the very low frequency
      (VLF) relative to the average standard values; the high proportion of students
      from 41% to 52%, with a mismatch of the sympathetic and parasympathetic
      compartments of the autonomic nervous system in the regulation of biological
      processes of adaptation. For medical students of higher education institutions
      there are typical functional reserves reduced from 20.5 % to 97.6% and a decrease
      in the proportion of students with a satisfactory adaptation by 40.4% from the 1
      to the 6th year.

PMID- 29446606
TI  - [Comparative characteristics of physical development of children and adolescents
      of the 1st and 2nd generation of European natives of the Magadan region].
AB  - In the paper there are presented results of investigations of indices of the
      physical development of male adolescents aged of 11-17 years - residents of the 1
      2 generation from new coming European migrants in the Magadan region during 2008
      2014. There were observed 418 adolescents - representatives of the 1 generation,
      and 463 cases from the 2 generation. Representatives of the 2 generation in the
      initial period (11-12 years) were established to show higher tempos of growth.
      Maximal gains in the body length, body mass, and chest circumference in
      adolescents of the 1 generation occur at the age of 13-14 years, but in the 2
      generation it is seen one year later - at the age of 14-15 years. In adolescents
      of each generation there was noted the high variability of the level of major
      indices of the physical development. However, among representatives of the 1
      generation there is less proportion of cases with normal or average values of
      body length, body mass, and chest circumference along with larger proportion
      ofpersons with diverse deviations, as well deficit as excess in comparison with
      the 2 generation. At the final stage of the puberty age (17 years) more
      adolescents with microsomatic (25%) and disharmonic (38.2%) body constitution
      occur among the subjects from the 1 generation as compared to those of the 2
      generation (19.7% and 28.2%, respectively).

PMID- 29446608
TI  - [First municipal sanitary stations in Russia: history and main activities (to the
      125th anniversary since foundation)].
AB  - First municipal sanitary stations in Russia were founded in 1891 in the cities of
      Moscow and St. Petersburg. They were financed by municipal public self
      governments. With performing essential laboratory tests and studies, stations
      were an important element of the organization of sanitary inspection in cities.
      In the article there is considered the history of the creation offirst sanitary
      stations and main directions of their activity: control in the sphere offood
      trade and in the sphere of municipal water supply.

PMID- 29446607
TI  - [Carbon nanotubes: mechanisms of the action, biological markers and evaluation of
      the (review of literature)].
AB  - The article contains the review and analysis of data on the mechanisms of the
      toxic action of carbon nanotubes (CNTs) on the body and available results of CNT
      toxicological evaluation after inhalation and oral routes of the action.
      Identification of cellular and molecular mechanisms of CNTs toxicity allows to
      justify the list of the most sensitive biochemical toxicity markers that could be
      used for monitoring the occupational effects of CNTs and serve as a promising
      target for the corresponding pharmacological and immunopharmacological
      interventions aimed on specific prophylaxis and therapy of diseases caused by
      CNT. A considerable amount of experimental data obtained in vivo on inhalation
      animal models allows to establish the hygienic standardfor CNT in the air of the
      working area. As to safe levels of the oral route of CNT it needs further study
      for their reliable assessment. The search and selection of sources for the review
      was executed with the use of public databases, including (in order of relevance)
      PubMed, Scopus, Google Scholar, and RISC, for the period from 2004 to 2017.

PMID- 29446609
TI  - [Evaluation of motor neuron excitability in lumbosacral spinal cord:
      Transcutaneous spinal cord stimulation as compared to H-reflex].
AB  - Multisegmental muscle responses (MMR) are reflexes in the leg muscles evoked by
      transcutaneous electrical spinal cord stimulation over the Th11-Th12 vertebrae.
      We have used MMR to evaluate the excitability of lumbosacral motor neurons in
      individuals suffering lower paraplegia. Ten individuals were tested using H
      reflexes and MMR bilaterally before (n 0 = 20) and during 4-weeks course of
      rehabilitation (n=76). The H-reflex and MMR of m. gastrocnemius lateralis were
      obtained in: 15 and 13 cases out of 20, respectively. Both reflexes were recorded
      in 11 and were absent in 3 cases, matched up to 70% of recordings. In dynamic,
      the both methods were 100% reproducible and the responses' amplitude varied in
      similar directions in 67% of records. The data confirm the validity and
      reproducibility of the MMR for evaluation of the motor neurons excitability in
      lumbosacral cord. The H-reflex magnitude shows moderate correlation with MMR in
      m. gastrocnemius lateralis (r = 0.59, p < 0.001), and low correlation with MMR in
      mm. rectus femoris, biceps femoris, and tibialis anterior (r < 0.40, p < 0.001).
      These findings do not allow extrapolate the results from the H-reflex measurement
      on the state of lumbosacral cord. At the same time, measurements of the MMR allow
      estimate simultaneously the excitability of motor pools innervating several
      muscle groups. This makes advantageous to assess the functional state of the
      motor neurons in the lumbosacral spinal cord for clinical and experimental
      studies, including the spinal cord damage.

PMID- 29446610
TI  - Self-Supported Stainless Steel Nanocone Array Coated with a Layer of Ni-Fe
      Oxides/(Oxy)hydroxides as a Highly Active and Robust Electrode for Water
      Oxidation.
AB  - Highly efficient, robust, and cheap water oxidation electrodes are of great
      significance for large-scale production of hydrogen by electrolysis of water.
      Here, a self-supported stainless steel (SS) nanocone array coated with a layer of
      nanoparticulate Ni-Fe oxides/(oxy)hydroxides was fabricated by a facile, low
      cost, and easily scalable two-step process. The construction of a nanocone array
      on the surface of an AISI 304 SS plate by acid corrosion greatly enlarged the
      specific surface area of the substrate, and the subsequent formation of a layer
      of Ni-Fe oxides/(oxy)hydroxides featuring the NiFe2O4 spinel phase on the
      nanocone surface by electrodeposition of [Ni(bpy)3]2+ significantly enhanced the
      intrinsic activity and the stability of the SS-based electrode. The as-prepared
      electrode demonstrated superior activity for the oxygen evolution reaction (OER)
      in 1 M KOH, with 232 and 280 mV overpotentials to achieve 10 and 100 mA cmgeo-2
      current densities, respectively. The high activity of the electrode was
      maintained over 340 h of chronopotentiometric test at 20 mA cmgeo-2, and the
      electrode also showed good stability over 100 h of electrolysis at high current
      density (200 mA cm-2). More important for practical application, the used SS
      based electrode can be easily regenerated with the original OER activity. The
      superior activity of this SS-based electrode stems from synergistic combination
      of high conductivity of the SS substrate, a large electrochemically active
      surface area of the nanocone array, and a uniformly coated nanoparticulate Ni-Fe
      oxide/(oxy)hydroxide layer with an optimal Ni/Fe ratio.

PMID- 29446611
TI  - Lithium-Ion Batteries: Charged by Triboelectric Nanogenerators with Pulsed Output
      Based on the Enhanced Cycling Stability.
AB  - The triboelectric nanogenerator (TENG) has been used to store its generated
      energy into lithium-ion batteries (LIBs); however, the influences of its pulse
      current and high voltage on LIB polarization and dynamic behaviors have not been
      investigated yet. In this paper, it is found that LIBs based on the phase
      transition reaction of the lithium storage mechanism [LiFePO4 (LFP) and Li4Ti5O12
      (LTO) electrodes] are more suitable for charging by TENGs. Thus, the enhanced
      cycling capacity, Coulombic efficiency (nearly 100% for LTO electrode), and
      energy storage efficiency (85.3% for the LFP-LTO electrode) are successfully
      achieved. Moreover, the pulse current has a positive effect on the increase of
      the Li-ion extraction, reducing the charge-transfer resistance ( Rct) for all
      studied electrodes as well (LFP, LiNi0.6Co0.2Mn0.2O2, LTO, and graphite). The
      excellent cyclability, high Coulombic, and energy storage efficiencies
      demonstrated the availability of storing pulsed energy generated by TENGs. This
      research has provided a promising analysis to obtain an enhanced charging
      methodology, which provides significant guidance for the scientific research of
      the LIBs.

PMID- 29446612
TI  - Total Capture, Convection-Limited Nanofluidic Immunoassays Exhibiting
      Nanoconfinement Effects.
AB  - Understanding nanoconfinement phenomena is necessary to develop nanofluidic
      technology platforms. One example of nanoconfinement phenomena is shifts in
      reaction equilibria toward reaction products in nanoconfined systems, which have
      been predicted theoretically and observed experimentally in DNA hybridization.
      Here we demonstrate a convection-limited nanofluidic immunoassay that achieves
      total capture of a target analyte and an apparent shift in the antibody-antigen
      reaction equilibrium due to nanoconfinement. The system exhibits wavefronts of
      the target analyte that propagate along the length of the nanochannel at a
      velocity much slower than that of the carrier fluid. We apply an analytical model
      describing the propagation of these wavefronts to determine the density of
      capture antibody binding sites in the enclosed nanochannel for a known
      concentration of the target analyte. We then use this binding site density to
      estimate the concentration of solutions with 5* and 10* less analyte. Our
      analysis suggests that nanoconfinement results in a preference toward binding of
      the target analyte with the surface-grafted capture antibody, as evidenced by an
      apparent reduction in the equilibrium dissociation constant. Our findings
      motivate the advancement of new biomedical and chemical synthesis technologies by
      leveraging nanoconfinement effects, and demonstrate a useful platform for
      studying the effect of nanoconfinement on chemical systems.

PMID- 29446613
TI  - Hierarchical FeNiP@Ultrathin Carbon Nanoflakes as Alkaline Oxygen Evolution and
      Acidic Hydrogen Evolution Catalyst for Efficient Water Electrolysis and Organic
      Decomposition.
AB  - Efficiency of hydrogen evolution via water electrolysis is mainly impeded by the
      kinetically sluggish oxygen evolution reaction (OER). Thus, it is of great
      significance to develop highly active and stable OER catalyst for alkaline water
      electrolysis or to substitute the more kinetically demanding acidic OER with a
      facile electron-donating reaction such that OER is no longer the bottleneck half
      reaction for either acidic or alkaline water electrolysis. Herein, the
      hierarchical Fe-Ni phosphide shelled with ultrathin carbon networks on Ni foam
      (FeNiP@C) is reported and shows exceptional OER activity and enhanced chemical
      stability in 1 M KOH. This unique electrode provides large active sites, facile
      electron transport pathways, and rapid gas release, resulting in a remarkable OER
      activity that delivers a current density of 100 mA/cm2 at an overpotential of 182
      mV with a Tafel slope of 56 mV/dec. Combining the hydrogen evolution reaction
      with organic pollutant (methylene blue) oxidation, a multifunctional electrolyzer
      for simultaneous cost-effective hydrogen generation and organic pollutant
      decomposition in acid wastewater is proposed. Our strategies in this work provide
      attractive opportunities in energy- and environment-related fields.

PMID- 29446614
TI  - Interpenetrated and Polythreaded CoII-Organic Frameworks as a Supercapacitor
      Electrode Material with Ultrahigh Capacity and Excellent Energy Delivery
      Efficiency.
AB  - Synthesizing kinetically stable coordination polymers (CPs) through ligand
      functionalization can effectively improve their supercapacitive performances.
      Herein, we have successfully synthesized three novel and topological Co-CPs by
      varying the flexible N-donor ligand and inorganic anions, namely, interpenetrated
      [Co(HTATB)( o-bib)].H2O, extended two-dimensional (2D) layered Co(HTATB)( m
      bib).2H2O, and three-dimensional (3D) Co(HTATB)( m-bib), where bib is the
      flexible N-donor bis((1 H-imidazol-1-yl)methyl)benzene linker (where o- and m-
      refer to ortho and meta positions, respectively) ligand and HTATB is the partial
      deprotonation mode from 4,4',4"- s-triazine-2,4,6-triyl-tribenzoic acid. Various
      Co-CPs have been directly applied in the field of supercapacitors. All these
      framework materials exhibit high capacitance, excellent energy delivery
      efficiency, and good cycling performance. For instance, the maximum specific
      capacitance for penetrated 3D networks is 2572 F g-1 at 2.0 A g-1, and the mean
      energy delivery efficiency is up to 92.7% based on the tested current densities.
      Compared with extensional 2D layered and 3D networks, the 3D interpenetrated and
      polythreaded architectures could provide more active sites and thus promote fast
      charging and discharging processes. Furthermore, the Li+ uptake-release abilities
      of the Co-based CPs are also investigated, and the initial discharge capacity
      value for the 3D interpenetrated structures can reach up to 1792 mA h g-1 at a
      current density of 50 mA g-1.

PMID- 29446615
TI  - Leveraging Engineering of Cells for Drug Delivery.
AB  - Cell therapy has become a momentum-gathering treatment strategy for a variety of
      diseases, including cancer, diabetes, hemophilia, and cardiomyopathy. However,
      clinical applications of conventional cell therapies have often been compromised
      by rapid decline in viability and function of the transplanted cells due to host
      recognition and subsequent foreign body rejection. Along this line, cell
      engineering technologies such as cell encapsulation within microcapsules and
      immobilization in porous scaffolds have been implemented to address the
      immunosuppression concerns. As a recent emerging research topic, drawing
      inspiration from the ways that natural cells interact with the body has opened
      new avenues for cell engineering, such as direct modification of whole cells with
      synthetic materials and "top-down" integration of biological membranes with
      micro/nanomaterials, which aim to alleviate immune response while harnessing the
      complex biological functions of cells. In this Account, we summarize our recent
      contribution to the field of cell engineering methodologies, with which we have
      demonstrated their promising applications for cancer immunotherapy, targeted drug
      delivery, and blood glucose regulation. For example, inspired by the inherent
      ability of platelets to accumulate at wound sites and interact with circulating
      tumor cells, we exploited a targeted checkpoint antibody delivery strategy for
      treatment of postsurgical cancer recurrence and metastatic spread by covalent
      binding of platelets' cell surfaces with a monoclonal antibody against programmed
      death ligand 1 (aPDL1). Without interfering with the platelets' surgical-site
      homing property, the conjugated aPDL1 could be triggered to release in the form
      of microparticles after in situ activation. As an extension, we then engineered
      the platelet membrane to cloak nanoparticles for anticancer drug delivery,
      mimicking the targeting capability of the source cells while possessing prolonged
      circulation lifetime and insignificant immunogenicity. At the same time, we also
      found that the subcellular compartment membrane-derived particulates exhibited
      high specificity toward homotypic cells, by which enhanced intracellular drug
      delivery was achieved. Moreover, by taking advantage of the reversible
      interaction between glucose-derivative-modified insulin and the red blood cell
      membrane, we constructed a glucose-responsive smart insulin delivery system for
      long-term maintenance of blood glucose levels within a normal range. Recently, by
      virtue of painless microneedle patches as convenient cell engineering platforms,
      a minimally invasive intradermal antitumor vaccine was invented by integrating
      whole-tumor lysis into near-infrared light-illuminated microneedle patches. The
      microneedle patches also showed promise in combining with conventional cell
      encapsulation techniques, by which an externally positioned beta-cell engineering
      strategy was proposed for diabetes treatment. The results presented in this
      Account demonstrate distinct approaches to the development and application of
      cell engineering strategies for drug delivery.

PMID- 29446617
TI  - Rapid, Stoichiometric, Site-Specific Modification of Aldehyde-Containing Proteins
      Using a Tandem Knoevenagel-Intra Michael Addition Reaction.
AB  - A site-specific modification of aldehyde-containing proteins using a tandem
      Knoevenagel-intra Michael addition reaction was developed. The reaction featured
      fast kinetics (50 M-1 s-1) and favorable stoichiometry. Various functionalities
      could be introduced into the protein with little impact on its function and
      conformation. The reaction was successfully applied in the labeling of living
      cells.

PMID- 29446616
TI  - New Mechanism for Release of Endosomal Contents: Osmotic Lysis via Nigericin
      Mediated K+/H+ Exchange.
AB  - Although peptides, antibodies/antibody fragments, siRNAs, antisense DNAs,
      enzymes, and aptamers are all under development as possible therapeutic agents,
      the breadth of their applications has been severely compromised by their
      inability to reach intracellular targets. Thus, while macromolecules can often
      enter cells by receptor-mediated endocytosis, their missions frequently fail due
      to an inability to escape their entrapping endosomes. In this paper, we describe
      a general method for promoting release of any biologic material from any
      entrapping endosome. The strategy relies on the fact that all nascent endosomes
      contain extracellular (Na+-enriched) medium, but are surrounded by intracellular
      (K+-enriched) fluid in the cytoplasm. Osmotic swelling and rupture of endosomes
      will therefore be facilitated if the flow of K+ down its concentration gradient
      from the cytosol into the endosome can be facilitated without allowing downhill
      flow of Na+ from the endosome into the cytosol. While any K+ selective ionophore
      can promote the K+ specific influx, the ideal K+ ionophore will also exchange
      influxed K+ for an osmotically inactive proton (H+) in order to prevent buildup
      of an electrical potential that would rapidly halt K+ influx. The only ionophore
      that catalyzes this exchange of K+ for H+ efficiently is nigericin. We
      demonstrate here that ligand-targeted delivery of nigericin into endosomes that
      contain an otherwise impermeable fluorescent dye can augment release of the dye
      into the cell cytosol via swelling/bursting of the entrapping endosomes. We
      further show that nigericin-facilitated escape of a folate-targeted luciferase
      siRNA conjugate from its entrapping endosomes promotes rapid suppression of the
      intended luciferase reporter gene. Taken together, we propose that ionophore
      catalyzed entry of K+ into endosomal compartments can promote the release of
      otherwise impermeable contents from their encapsulating endosomes.

PMID- 29446618
TI  - Correction to All-in-One Centrifugal Microfluidic Device for Size-Selective
      Circulating Tumor Cell Isolation with High Purity.

PMID- 29446619
TI  - Synthesis of Cyclic Peptides as Potential Anti-Malarials.
AB  - The results from the synthesis of peptides by Fmoc/SPPS on a 2-CTC resin and then
      lactamization in solution or solid phase for the preparation of cyclopeptides are
      presented. Both procedures allow the synthesis of the desired compounds in good
      to very good yield and with high cyclization efficiency for on-resin
      macrocyclization. In addition, the activities of the corresponding cyclopeptides
      against the chloroquine-resistant K1 strain of Plasmodium falciparum were
      evaluated. Cyclo-Cys(Trt)-Gly-Thr( tBu)-Gly-Cys(Trt)-Gly showed potent in vitro
      and selective activity against this parasite, EC50 = 28 nM.

PMID- 29446620
TI  - Polydopamine-Coated Main-Chain Liquid Crystal Elastomer as Optically Driven
      Artificial Muscle.
AB  - Optically driven active materials have received much attention because their
      deformation and motion can be controlled remotely, instantly, and precisely in a
      contactless way. In this study, we investigated an optically actuated elastomer
      with rapid response: polydopamine (PDA)-coated liquid crystal elastomer (LCE).
      Because of the photothermal effect of PDA coating and thermal responsiveness of
      LCE, the elastomer film contracted significantly with near-infrared (NIR)
      irradiation. With a fixed strain, light-induced actuating stress in the film
      could be as large as 1.5 MPa, significantly higher than the maximum stress
      generated by most mammalian skeletal muscle (0.35 MPa). The PDA-coated LCE films
      could also bend or roll up by surface scanning of an NIR laser. The response time
      of the film to light exposure could be as short as 1/10 of a second, comparable
      to or even faster than that of mammalian skeletal muscle. Using the PDA-coated
      LCE film, we designed and fabricated a prototype of robotic swimmer that was able
      to swim near the water-air interface by performing "swimming strokes" through
      reversible bending and unbending motions induced and controlled by an NIR laser.
      The results presented in this study clearly demonstrated that PDA-coated LCE is a
      promising optically driven artificial muscle, which may have great potential for
      applications of soft robotics and optomechanical coupling devices.

PMID- 29446621
TI  - Oxidative Dehydrogenation on Nanocarbon: Insights into the Reaction Mechanism and
      Kinetics via in Situ Experimental Methods.
AB  - Sustainable and environmentally benign catalytic processes are vital for the
      future to supply the world population with clean energy and industrial products.
      The replacement of conventional metal or metal oxide catalysts with earth
      abundant and renewable nonmetallic materials has attracted considerable research
      interests in the field of catalysis and material science. The stable and
      efficient catalytic performance of nanocarbon materials was discovered at the end
      of last century, and these materials are considered as potential alternatives for
      conventional metal-based catalysts. With its rapid development in the past 20
      years, the research field of carbon catalysis has been experiencing a smooth
      transition from the discovery of novel nanocarbon materials or related new
      reaction systems to the atomistic-level mechanistic understanding on the
      catalytic process and the subsequent rational design of the practical catalytic
      reaction systems. In this Account, we summarize the recent progress in the
      kinetic and mechanistic studies on nanocarbon catalyzed alkane oxidative
      dehydrogenation (ODH) reactions. The paper attempts to extract general concepts
      and basic regularities for carbon catalytic process directing us on the way for
      rational design of novel efficient metal-free catalysts. The nature of the active
      sites for ODH reactions has been revealed through microcalorimetric analysis,
      ambient pressure X-ray photoelectron spectroscopy (XPS) measurement, and in situ
      chemical titration strategies. The detailed kinetic analysis and in situ catalyst
      structure characterization suggests that carbon catalyzed ODH reactions involve
      the redox cycles of the ketonic carbonyl-hydroxyl pairs, and the key
      physicochemical parameters (activation energy, reaction order, and
      rate/equilibrium constants, etc.) of the carbon catalytic systems are proposed
      and compared with conventional transition metal oxide catalysts. The proposal of
      the intrinsic catalytic activity (TOF) provides the possibility for the fair
      comparisons of different nanocarbon catalysts and the consequent structure
      function relation regularity. Surface modification and heteroatom doping are
      proved as the most effective strategies to adjust the catalytic property
      (activity and product selectivity etc.) of the nanocarbon catalysts. Nanocarbon
      is actually a proper candidate platform helping us to understand the classical
      catalytic reaction mechanism better, since there is no lattice oxygen and all the
      catalytic process happens on nanocarbon surface. This Account also exhibits the
      importance of the in situ structural characterizations for heterogeneous
      nanocarbon catalysis. The research strategy and methods proposed for carbon
      catalysts may also shed light on other complicated catalytic systems or fields
      concerning the applications of nonmetallic materials, such as energy storage and
      environment protection etc.

PMID- 29446622
TI  - Hyper-Cross-linked Porous MoS2-Cyclodextrin-Polymer Frameworks: Durable Removal
      of Aromatic Phenolic Micropollutant from Water.
AB  - A reasonable and efficient strategy for the construction of hyper-cross-linked
      porous MoS2-CD-polymer frameworks (MoS2CDPFs) was demonstrated. Here, MoS2
      nanosheets (NSs) can be decorated with amino functionalized beta-cyclodextrin,
      producing a nanoscale structural motif (MoS2@CD) for the synthesis of MoS2CDPFs.
      We demonstrated that CD polymer (CDP) as linker can be uniformly incorporated
      into the frameworks. Except for the pores created between MoS2 NSs, polymer
      doping generates extra interspace between MoS2 NSs and CD monomer. Interestingly,
      the resultant MoS2CDPFs can rapidly sequester aromatic phenolic micropollutant
      bisphenol A (0.1 mM) from water with 93.2% adsorption capacity, which is higher
      than that of MoS2, MoS2@CD, and CDP. The intercalation between MoS2 sheets with
      CDP imparts the frameworks durability in adsorption/desorption of aromatic
      phenolic micropollutants. Remarkably, the removal efficiency reduced only 3%
      after 10 regeneration-reuse cycles. These findings demonstrated that the porous
      MoS2-CD-polymer-based frameworks are promising adsorbents for rapid, flow-through
      water remediation.

PMID- 29446623
TI  - Photocontrolled Coumarin-diphenylalanine/Cyclodextrin Cross-Linking of 1D
      Nanofibers to 2D Thin Films.
AB  - Using coumarin-modified diphenylalanine (CO-FF) and gamma-cyclodextrin (gamma-CD)
      as building blocks, we successfully constructed one-dimensional nanofibers with
      several nanometers in width and tens of micrometers in length. Through the
      photodimerization of coumarin units in CO-FF?gamma-CD complexes, the resultant
      nanofibers could be cross-linked to organic 2D thin films with a lateral
      dimension of tens of micrometers and a thickness of nanometers. The resultant
      thin films exhibited a significant fluorescence enhancement for twisted
      intramolecular charge-transfer (TICT) molecules and effective removal of
      pollutant from water through filtration. This 1D -> 2D morphological conversion
      controlled by light may provide a novel strategy to construct the highly ordered
      nanostructures that can be used as templates for making nanoscaled materials with
      defined sizes and shapes.

PMID- 29446624
TI  - Hydrogen-Assisted Growth of Large-Area Continuous Films of MoS2 on Monolayer
      Graphene.
AB  - We show how control over the chemical vapor deposition (CVD) reaction chemistry
      of molybdenum disulfide (MoS2) by hydrogen addition can enable the direct growth
      of centimeter-scale continuous films of vertically stacked MoS2 monolayer on
      graphene under atmospheric pressure conditions. Hydrogen addition enables longer
      CVD growth times at high temperature by reducing oxidation effects that would
      otherwise degrade the monolayer graphene. By careful control of nucleation
      density and growth time, high-quality monolayer MoS2 films could be formed on
      graphene, realizing all CVD-grown vertically stacked monolayer
      semimetal/semiconducting interfaces. Photoluminescence spectroscopy shows
      quenching of MoS2 by the underlying graphene, indicating a good interfacial
      charge transfer. We utilize the MoS2/graphene vertical stacks as photodetectors,
      with photoresponsivities reaching 2.4 A/W under 135 MUW 532 nm illumination. This
      approach provides insights into the scalable manufacturing of high-quality two
      dimensional electronic and optoelectronic devices.

PMID- 29446625
TI  - Porous Metal-Organic Frameworks with Chelating Multiamine Sites for Selective
      Adsorption and Chemical Conversion of Carbon Dioxide.
AB  - A combination of carbon dioxide (CO2) capture and chemical fixation in a one-step
      process is attractive for chemists and environmentalists. In this work, by
      incorporating chelating multiamine sites to enhance the binding affinity toward
      CO2, two novel metal-organic frameworks (MOFs) [Zn2(L)(2,6
      NDC)2(H2O)].1.5DMF.2H2O (1) and [Cd2(L)(2,6-NDC)2].1.5DMF.2H2O (2) (L = N1-(4-(1
      H-1,2,4-triazole-1-yl)benzyl)- N1-(2-aminoethyl)ethane-1,2-diamine, 2,6-H2NDC =
      2,6-naphthalenedicarboxylic acid, DMF = N, N-dimethylformamide) were achieved
      under solvothermal conditions. Both 1 and 2 possess high selectivity for
      adsorption of CO2 over CH4 at room temperature under atmospheric pressure.
      Moreover, 1 has one-dimensional tubular channels decorated with multiactive sites
      including NH2 groups and coordination unsaturated Lewis acid metal sites, leading
      to efficient catalytic activity for chemical fixation of CO2 by reaction with
      epoxides to give cyclic carbonates under mild conditions.

PMID- 29446626
TI  - Correction to "Direct Electrochemical Measurements of Reactive Oxygen and
      Nitrogen Species in Nontransformed and Metastatic Human Breast Cells".

PMID- 29446627
TI  - Ultrabright and Fluorogenic Probes for Multicolor Imaging and Tracking of Lipid
      Droplets in Cells and Tissues.
AB  - Lipid droplets (LDs) are intracellular lipid-rich organelles that regulate the
      storage of neutral lipids and were recently found to be involved in many
      physiological processes, metabolic disorders, and diseases including obesity,
      diabetes, and cancers. Herein we present a family of new fluorogenic merocyanine
      fluorophores based on an indolenine moiety and a dioxaborine barbiturate
      derivative. These so-called StatoMerocyanines (SMCy) fluoresce from yellow to the
      near-infrared (NIR) in oil with an impressive fluorescence enhancement compared
      to aqueous media. Additionally, SMCy display remarkably high molar extinction
      coefficients (up to 390 000 M-1 cm-1) and high quantum yield values (up to 100%).
      All the members of this new family specifically stain the LDs in live cells with
      very low background noise. Unlike Nile Red, a well-known lipid droplet marker,
      SMCy dyes possess narrow absorption and emission bands in the visible, thus
      allowing multicolor imaging. SMCy proved to be compatible with fixation and led
      to high-quality 3D images of lipid droplets in cells and tissues. Their high
      brightness allowed efficient tissue imaging of adipocytes and circulating LDs.
      Moreover their remarkably high two-photon absorption cross-section, especially
      SMCy5.5 (up to 13 300 GM), as well as their capacity to efficiently fluoresce in
      the NIR region led to two-photon multicolor tissue imaging (liver). Taking
      advantage of the available color palette, lipid droplet exchange between cells
      was tracked and imaged, thus demonstrating intercellular communication.

PMID- 29446628
TI  - Barriers to Rotation in ortho-Substituted Tertiary Aromatic Amides: Effect of
      Chloro-Substitution on Resonance and Distortion.
AB  - Planarity of the amide bond represents one of the most widely recognized
      properties of amides. Herein, we report a combined structural and computational
      study on the effect of ortho-substitution on resonance and barriers to rotation
      in tertiary aromatic amides. We demonstrate that ortho-chloro substitution in a
      class of benzamides that are important from the reactivity and medicinal
      chemistry perspective results in increased barriers to rotation around both the N
      C(O) and C-C(O) axes. The effect of steric hindrance on structures, resonance
      energies, barriers to rotation, and proton affinities is discussed. The present
      study strongly supports the use of ortho-substitution in common benzamides to
      strengthen amidic resonance.

PMID- 29446629
TI  - Microplastics in Swiss Floodplain Soils.
AB  - Microplastics (MPs) are small (<5 mm diameter) but have clear implications for
      the environment. These artificial particles are found in and pose threats to
      aquatic systems worldwide. MPs have terrestrial sources, but their concentrations
      and fates in the terrestrial environment are poorly understood. While global
      plastic production continues to increase, so do the environmental concentrations
      and impacts of MPs. In this first study of MPs in floodplain soils, we developed
      a method for identifying, quantifying, and measuring the sizes of most commonly
      produced MPs in soil by FT-IR microscopy. For small MP (<1 mm) analysis, MP were
      separated by density separation and oxidation of organic matter. In this study we
      analyzed 29 floodplains in Swiss nature reserves associated with catchments
      covering 53% of Switzerland. We found evidence that 90% of Swiss floodplain soils
      contain MPs. The highest MP concentrations were associated with the concentration
      of mesoplastics (5 mm - 2.5 cm diameter), indicating plastic waste as source.
      Furthermore, MP concentration was correlated with the population of the
      catchment. The wide distribution of MPs, their presence in remote unsettled high
      mountain areas, decoupling of MEP and MP compositions, and the dominance of MPs
      by small (<500 MUm diameter) particles, indicate that MPs enter soils via diffuse
      aeolian transport.

PMID- 29446630
TI  - Lanthanum-Doped Hafnium Oxide: A Robust Ferroelectric Material.
AB  - Recently simulation groups have reported the lanthanide series elements as the
      dopants that have the strongest effect on the stabilization of the ferroelectric
      non-centrosymmetric orthorhombic phase in hafnium oxide. This finding confirms
      experimental results for lanthanum and gadolinium showing the highest remanent
      polarization values of all hafnia-based ferroelectric films until now. However,
      no comprehensive overview that links structural properties to the electrical
      performance of the films in detail is available for lanthanide-doped hafnia.
      La:HfO2 appears to be a material with a broad window of process parameters, and
      accordingly, by optimization of the La content in the layer, it is possible to
      improve the performance of the material significantly. Variations of the La
      concentration leads to changes in the crystallographic structure in the bulk of
      the films and at the interfaces to the electrode materials, which impacts the
      spontaneous polarization, internal bias fields, and with this the field cycling
      behavior of the capacitor structure. Characterization results are compared to
      other dopants like Si, Al, and Gd to validate the advantages of the material in
      applications such as semiconductor memory devices.

PMID- 29446632
TI  - Atmospheric Arsenic Deposition in the Pearl River Delta Region, South China:
      Influencing Factors and Speciation.
AB  - This is a comprehensive study on mobilization/speciation and temporal/spatial
      variation of atmospheric arsenic (As) deposition in the Pearl River Delta (PRD)
      region. A set of experimental procedures was established for measuring the
      deposition fluxes of individual As species. The deposition carrying inorganic
      AsIII % was significantly higher than that contained in atmospheric particles.
      Compared with dry deposition, wet deposition was much more harmful to the
      regional ecosystem, as it contributed the majority of bulk deposition (>75%) and
      carried most of the mobilized iAsIII compounds. A stepwise linear regression
      model was utilized to identify the factors influencing total As deposition (wet:
      precipitation and PM2.5, dry: relative humidity, wind speed, and PM10, bulk:
      precipitation, PM2.5, and wind speed). By examining the representativeness of the
      study sites and comparison with the literature data, the statistic models were
      verified to explain the temporal/spatial variation of total As deposition in the
      entire PRD region, where significant seasonal variation was only found for wet
      deposition (wet season > dry season). The annual As load contributed from
      regional atmospheric deposition increased from 2013 to 2015, when the
      contributions of individual cities varied annually.

PMID- 29446631
TI  - Mechanistic Investigation and Multiplexing of Liposome-Assisted Metabolic Glycan
      Labeling.
AB  - Metabolic labeling of glycans with bioorthogonal reporters has been widely used
      for glycan imaging and glycoproteomic profiling. One of the intrinsic limitations
      of metabolic glycan labeling is the lack of cell-type selectivity. The recently
      developed liposome-assisted bioorthogonal reporter (LABOR) strategy provides a
      promising means to overcome this limitation, but the mechanism of LABOR has not
      been investigated in detail. In this work, we performed a mechanistic study on
      LABOR and explored its multiplexing capability. Our studies support an
      endocytosis-salvage mechanism. The ligand-targeted liposomes encapsulating
      azidosugars are internalized into the endosome via the receptor-mediated
      endocytosis. Unlike the conventional drug delivery, LABOR does not rely on the
      endosomal escape pathways. Rather, the liposomes are allowed to enter the
      lysosome, inside which the azidosugars are released from the liposomes. The
      released azidosugars then intercept the salvage pathways of monosaccharides and
      get transported into the cytosol by lysosomal sugar transporters. Based on this
      mechanism, we expanded the scope of LABOR by evaluating a series of ligand
      receptor pairs for targeting sialoglycans in various cell types. Different ligand
      types including small molecules, antibodies, aptamers, and peptides could be
      easily implemented into LABOR. Finally, we demonstrated that the sialoglycans in
      two distinct cell populations in a co-cultured system could be selectively
      labeled with two distinct chemical reporters by performing a multiplexed LABOR
      labeling.

PMID- 29446633
TI  - Molecular Dynamics Study of the Solution Structure, Clustering, and Diffusion of
      Four Aqueous Alkanolamines.
AB  - CO2 sequestration from anthropogenic resources is a challenge to the design of
      environmental processes at a large scale. Reversible chemical absorption by amine
      based solvents is one of the most efficient methods of CO2 removal. Molecular
      simulation techniques are very useful tools to investigate CO2 binding by aqueous
      alkanolamine molecules for further technological application. In the present
      work, we have performed detailed atomistic molecular dynamics simulations of
      aqueous solutions of three prototype amines: monoethanolamine (MEA) as a
      standard, 3-aminopropanol (MPA), 2-methylaminoethanol (MMEA), and 4-diethylamino
      2-butanol (DEAB) as potential novel CO2 absorptive solvents. Solvent densities,
      radial distribution functions, cluster size distributions, hydrogen-bonding
      statistics, and diffusion coefficients for a full range of mixture compositions
      have been obtained. The solvent densities and diffusion coefficients from
      simulations are in good agreement with those in the experiment. In aqueous
      solution, MEA, MPA, and MMEA molecules prefer to be fully solvated by water
      molecules, whereas DEAB molecules tend to self-aggregate. In a range from 30/70
      50/50 (w/w) alkanolamine/water mixtures, they form a bicontinuous phase (both
      alkanolamine and water are organized in two mutually percolating clusters). Among
      the studied aqueous alkanolamine solutions, the diffusion coefficients decrease
      in the following order MEA > MPA = MMEA > DEAB. With an increase of water
      content, the diffusion coefficients increase for all studied alkanolamines. The
      presented results are a first step for process-scale simulation and provide
      important qualitative and quantitative information for the design and engineering
      of efficient new CO2 removal processes.

PMID- 29446634
TI  - Correction to "Hierarchically Patterned Noncovalent Functionalization of 2D
      Materials by Controlled Langmuir-Schaefer Conversion".

PMID- 29446635
TI  - Unmasking Dipole Character of Acyl Ketene Dithioacetals via a Cascade Reaction
      with Arynes: Synthesis of Benzo[b]thiophenes.
AB  - An unusual strategy toward novel substituted benzo[b]thiophenes has been
      developed. The generation of arynes in the presence of acyl ketene dithioacetals
      resulted in a cascade reaction involving [3 + 2] cycloaddition, and a
      dealkylative arylation of a thioether moiety to afford 2,3-disubstuted
      benzo[b]thiophenes. This route represents an expeditious approach to
      benzothiophenes that employs acyl ketene dithioacetals as dipoles.

PMID- 29446636
TI  - Mapping the Extra Solvent Power of Ionic Liquids for Monomers, Polymers, and
      Dry/Wet Globular Single-Chain Polymer Nanoparticles.
AB  - Ionic liquids (ILs) have shown advantages in organic synthesis and catalysis,
      energy storage and conversion, and a variety of pharmaceutical applications.
      Understanding the miscibility behavior of IL/monomer, IL/polymer, and IL/polymer
      nanoparticle mixtures is critical for the use of ILs as green solvents in
      polymerization processes as well as to rationalize recent observations concerning
      the superior solubility of some proteins in ILs when compared to standard
      solvents. In this work, the most relevant results obtained in terms of extended
      three-component Flory-Huggins theory concerning the extra solvent power (ESP) of
      ILs when compared to traditional nonionic solvents for monomeric solutes (Case
      I), linear polymers (Case II), dry (i.e., without IL inside) globular single
      chain polymer nanoparticles (SCNPs) (Case III), and wet (i.e., with IL inside)
      globular SCNPs (Case IV) are presented. Moreover, useful ESP maps are drawn for
      the first time for IL mixtures corresponding to Cases I, II, III, and IV at a
      constant temperature and pressure. Finally, a potential pathway to improve the
      miscibility of nonionic polymers in ILs is proposed.

PMID- 29446637
TI  - alpha-Alkylation of Chiral Sulfinimines for Constructing Quaternary Chiral
      Carbons by Introducing Removable Directing Groups.
AB  - This study developed a facile and efficient synthetic strategy to construct
      quaternary chiral centers at the alpha-position of imines and ketones. High
      regioselectivity and diastereoselectivity were achieved through the synergetic
      effect of electron-withdrawing directing groups and N-tert-butyl sulfinamide as
      chiral auxiliaries. Either of them could be removed under the optimized
      conditions without any epimerization.

PMID- 29446638
TI  - Chiral-at-Metal Rh(III) Complex-Catalyzed Michael Addition of Pyrazolones with
      alpha,beta-Unsaturated 2-Acyl Imidazoles.
AB  - An efficient enantioselective conjugate addition of pyrazolones with alpha,beta
      unsaturated 2-acyl imidazoles catalyzed by chiral-at-metal rhodium complex is
      reported. The corresponding adducts were obtained in good yields (85%-96%) with
      excellent enantioselectivities (up to >99%). This protocol exhibits extraordinary
      reactivity, because of the fact that a complex with as little as 0.05 mol %
      Rh(III) can catalyze the title reaction on a gram-scale with excellent
      enantioselectivity.

PMID- 29446639
TI  - Two-Dimensional Electronic Spectroscopy Reveals Dynamics and Mechanisms of
      Solvent-Driven Inertial Relaxation in Polar BODIPY Dyes.
AB  - In this work, we demonstrate the use of two-dimensional electronic spectroscopy
      (2DES) to study the mechanism and time scale of the femtosecond Stokes shift
      dynamics in molecules characterized by intramolecular charge transfer, such as
      distyryl-functionalized boron dipyrromethene (BODIPY) molecules. The obtained
      results demonstrate that 2DES allows clear and direct visualization of the
      phenomenon. The analysis of the 2D data in terms of 2D frequency-frequency decay
      associated maps provides indeed not only the time scale of the relaxation process
      but also the starting and the final point of the energy flow and the associated
      reorganization energy, identified by looking at the coordinates of a negative
      signature below the diagonal. The sensitivity of the 2DES technique to
      vibrational coherence dynamics also allowed the identification of a possible
      relaxation mechanism involving specific interaction between a vibrational mode of
      the dye and the solvent.

PMID- 29446640
TI  - Asymmetric Total Synthesis of (+)-Majusculoic Acid via a Dimerization
      Dedimerization Strategy and Absolute Configuration Assignment.
AB  - The first total synthesis of (+)-majusculoic acid, the enantiomer of naturally
      occurring antifungal cyclopropane fatty acid (-)-majusculoic acid, was
      accomplished in 13 steps, leading to the assignment of the absolute configuration
      of the natural product. The synthesis featured a ring closing metathesis
      dimerization, a conformationally controlled cyclopropanation, a dedimerization,
      and a bromoolefination.

PMID- 29446641
TI  - Persistent mania following cessation of corticosteroids.
AB  - OBJECTIVES: The aims of this study are to describe two patients whose manic
      symptoms persisted for several months after the cessation of corticosteroids, to
      review the literature and to suggest treatment. METHODS: The presentation of two
      elderly patients with persistent manic symptoms following cessation of
      corticosteroids several months previously afforded the author the opportunity to
      examine them carefully, investigate and treat them. RESULTS: The patients were
      investigated to rule out other causes and were treated with sodium valproate and
      quetiapine (in the second patient). When well, the medications were slowly
      decreased and stopped. Both patients were well at one-year follow-up.
      CONCLUSIONS: Manic symptoms may persist for many months after stopping
      corticosteroids and active treatment is needed to control them.

PMID- 29446642
TI  - Revealing the dual role of gallic acid in modulating ampicillin sensitivity of
      Pseudomonas aeruginosa biofilms.
AB  - AIM: To understand the effects of gallic acid (GA) on ampicillin (Amp) sensitive
      or resistant strain of Pseudomonas sp. and also in modulating the corresponding
      biofilms. METHODOLOGY: The cell viability was determined by broth dilution, dry
      weight and CFU assays. Biofilm formation was measured by crystal violet assay
      while oxygen consumption rate was measured to verify the metabolic status of the
      cells. The membrane damage and drug efflux/accumulation were studied by
      fluorimetric assays. RESULTS: GA transformed the Amp resistant cells, both
      planktonic and biofilms, into highly sensitive one by inducing membrane damage
      and enhancing accumulation of drug, whereas the Amp sensitive cells gained
      resistance against Amp. CONCLUSION: Use of GA as an antimicrobial compound should
      be analyzed more critically depending on the drug dosages, drug sensitivity as
      well as types of bacterial strains being studied.

PMID- 29446643
TI  - Traditional consumption of and rearing edible insects in Africa, Asia and Europe.
AB  - The traditional consumption of edible insects is common in one third of the
      world's population, mostly in Latin America, Africa and Asia. There are over one
      thousand identified species of insects eaten in some stage of their life cycle;
      and they play important roles in ensuring food security. The most common way to
      collect insects are from the wild, which is seasonal with limited availability
      and has an increasing demand resulting in a disruption to the ecosystem. There is
      a growing interest shown in rearing insects for commercial purposes, and an
      industrial scale production will be required to ensure steady supplies.
      Industrial production will need to take into account the living environment of
      insects, the nutritional composition of their feed and the overall efficiency of
      the production system. We provide a short overview on the consumption of and
      rearing insects in Africa, Asia and Europe. For Africa, a snapshot is given for
      Nigeria, Ghana, Central African Republic, Kenya and Uganda, while the following
      countries are reported for Asia: China, Japan, Lao People's Democratic Republic,
      Thailand and Vietnam. In addition, a list of insect species with the highest
      potential for food and feed in the European Union is provided with some reference
      to The Netherlands and Finland. The review concludes that there is need to better
      understand the rearing and farming procedures that will yield high quality edible
      insects in Africa, Asia and Europe.

PMID- 29446644
TI  - An algorithm for managing adults who refuse medical treatment in New South Wales.
AB  - OBJECTIVES: The assessment and management of a patient who refuses medical
      treatment requires clinical skill, and consideration of the relevant law and the
      patient's decision-making capacity. Psychiatrists are often asked to advise in
      these situations. We aimed to develop an algorithm describing the relevant legal
      pathways to assist clinicians, especially psychiatrists, working in New South
      Wales (NSW), Australia. METHODS: We reviewed the academic literature on treatment
      refusal, relevant legislation, judicial rulings and NSW Health policy directives
      and guidelines. We consulted with clinicians and representatives of relevant
      tribunals. RESULTS: We developed an algorithm for managing patients who refuse
      medical treatment in NSW. The algorithm emphases the evaluation of decision
      making capacity and tracks separate pathways depending upon a person's status
      under the Mental Health Act 2007 (NSW). CONCLUSIONS: The algorithm provides a
      clear decision tree for clinicians responding to a patient refusing medical
      treatment in NSW.

PMID- 29446646
TI  - Accuracy of flash glucose monitoring and continuous glucose monitoring
      technologies: Implications for clinical practice.
AB  - Continuous glucose monitoring and flash glucose monitoring technologies measure
      glucose in the interstitial fluid and are increasingly used in diabetes care.
      Their accuracy, key to effective glycaemic management, is usually measured using
      the mean absolute relative difference of the interstitial fluid sensor compared
      to reference blood glucose readings. However, mean absolute relative difference
      is not standardised and has limitations. This review aims to provide a consensus
      opinion on assessing accuracy of interstitial fluid glucose sensing technologies.
      Mean absolute relative difference is influenced by glucose distribution and rate
      of change; hence, we express caution on the reliability of comparing mean
      absolute relative difference data from different study systems and conditions. We
      also review the pitfalls associated with mean absolute relative difference at
      different glucose levels and explore additional ways of assessing accuracy of
      interstitial fluid devices. Importantly, much data indicate that current practice
      of assessing accuracy of different systems based on individualised mean absolute
      relative difference results has limitations, which have potential clinical
      implications. Healthcare professionals must understand the factors that influence
      mean absolute relative difference as a metric for accuracy and look at additional
      assessments, such as consensus error grid analysis, when evaluating continuous
      glucose monitoring and flash glucose monitoring systems in diabetes care. This in
      turn will ensure that management decisions based on interstitial fluid sensor
      data are both effective and safe.

PMID- 29446645
TI  - The relationship of perivascular adipose tissue and atherosclerosis in the aorta
      and carotid arteries, determined by magnetic resonance imaging.
AB  - BACKGROUND AND AIMS: Imaging studies have relied on the 'overall' volumetric
      quantification of perivascular adipose tissue. We sought to assess the
      relationship of circumferential distribution between perivascular adipose tissue
      and adjacent wall thickness of carotid and aortic arteries using dedicated
      magnetic resonance imaging sequences. METHODS: Vessel wall and perivascular
      adipose tissue were acquired using magnetic resonance imaging (1.5 T). Co
      registered images were segmented separately, and measurements of both
      perivascular adipose tissue and vessel wall were obtained along radii of the
      vessel spaced at angles of 5 degrees  each. RESULTS: In total, 29 patients were
      recruited. Perivascular adipose tissue thickness of the aorta was 3.34 +/- 0.79
      mm with specific pattern of 'double peaks' distribution, while carotid
      perivascular adipose tissue had no identifiable pattern with thickness of 0.8 +/-
      0.91 mm. Although statistically significant, the correlation between perivascular
      adipose tissue thickness and wall thickness in carotid arteries with normal (r =
      0.040, p = 0.001) or with abnormal wall thickness (r = -0.039, p = 0.015) was
      merely nominal. Similarly, perivascular adipose tissue of the aorta had very weak
      correlation with normal aortic wall thickness (r = 0.010, p = 0.008) but not with
      the abnormal ones (r = -0.05, p = 0.29). CONCLUSION: Dissociation between the
      spatial distribution of perivascular adipose tissue and arterial wall thickening
      in the aorta and carotid arteries does not support that perivascular adipose
      tissue has a causal role in promoting atherosclerotic plaque via a paracrine
      route. Yet, perivascular adipose tissue functional properties were not examined
      in this study.

PMID- 29446648
TI  - Electromagnetic Field Could Protect SH-SY5Y Cells Against Cisplatin Cytotoxicity,
      But Not MCF-7 Cells.
AB  - Cisplatin [cis-dichlorodiammine platinum (II), CDDP], morphine (Mor), and
      electromagnetic field (EMF) induced oxidative stress. In this study, we tried to
      increase the cytotoxicity of CDDP in combination with Mor and/or EMF in MCF-7 and
      SH-SY5Y cells. Furthermore, we evaluate the expression levels of 11 antioxidant
      genes in both cell lines. We designed four treatments: CDDP alone, "CDDP+Mor,"
      "CDDP+EMF," and "CDDP+Mor+EMF." Serial dilutions of CDDP, Mor (5.0 MUM), and EMF
      (50 Hz, 0.50 mT, "15 min field-on/15 min field-off") were used for estimation of
      relative IC50 values. The mRNA expression levels of antioxidant genes were
      determined by real-time PCR. The IC50 value of CDDP in "CDDP+Mor+EMF" treatment
      was significantly higher than CDDP alone and "CDDP+Mor" treatments in both cell
      lines. Whereas the expression levels of antioxidant genes in the four treatments
      showed similar patterns in MCF-7 cells, in SH-SY5Y cells, most of the antioxidant
      genes showed an upregulation with "CDDP+EMF" and "CDDP+Mor+EMF" treatments.
      Moreover, significant differences in the number of upregulated genes were
      observed between different treatments in SH-SY5Y cells. The molecular mechanism
      of CDDP-reduced cytotoxicity in our designed combinations is probably different
      in MCF-7 and SH-SY5Y cells. CDDP in combination with EMF could protect SH-SY5Y
      cells from the cytotoxicity, whereas it has no significant change in MCF-7 cells.

PMID- 29446649
TI  - How to relieve breathing difficulties in high-temperature conditions for heart
      disease patients.

PMID- 29446650
TI  - Methods for culturing anaerobes from human specimen.
AB  - Anaerobes represent the dominating population in the human gut microbiota and
      play a key role in gut homeostasis. In addition, several anaerobes are now
      considered as probiotics and they remain essential to several processes in the
      field of biotechnology. With the implementation of MALDI-TOF MS in routine
      laboratories, anaerobes are no longer neglected in clinical microbiology, as
      their identification is made easy. However, the isolation and identification of
      anaerobic bacteria, remains time consuming, fastidious and costly. Various
      strategies have been developed, from sampling to culturing human specimens, which
      will be discussed in this paper. Also, particular attention is paid to isolating
      species with special medical importance, as for contribution to the field of
      culturomics.

PMID- 29446647
TI  - Management of Multi-Casualty Incidents in Mountain Rescue: Evidence-Based
      Guidelines of the International Commission for Mountain Emergency Medicine (ICAR
      MEDCOM).
AB  - : Blancher, Marc, Francois Albasini, Fidel Elsensohn, Ken Zafren, Natalie Holzl,
      Kyle McLaughlin, Albert R. Wheeler III, Steven Roy, Hermann Brugger, Mike Greene,
      and Peter Paal. Management of multi-casualty incidents in mountain rescue:
      Evidence-based guidelines of the International Commission for Mountain Emergency
      Medicine (ICAR MEDCOM). High Alt Med Biol. 19:131-140, 2018. INTRODUCTION: Multi
      Casualty Incidents (MCI) occur in mountain areas. Little is known about the
      incidence and character of such events, and the kind of rescue response.
      Therefore, the International Commission for Mountain Emergency Medicine (ICAR
      MEDCOM) set out to provide recommendations for the management of MCI in mountain
      areas. MATERIALS AND METHODS: Details of MCI occurring in mountain areas related
      to mountaineering activities and involving organized mountain rescue were
      collected. A literature search using (1) PubMed, (2) national mountain rescue
      registries, and (3) lay press articles on the internet was performed. The results
      were analyzed with respect to specific aspects of mountain rescue. RESULTS: We
      identified 198 MCIs that have occurred in mountain areas since 1956: 137
      avalanches, 38 ski lift accidents, and 23 other events, including lightning
      injuries, landslides, volcanic eruptions, lost groups of people, and water
      related accidents. DISCUSSION: General knowledge on MCI management is required.
      Due to specific aspects of triage and management, the approach to MCIs may differ
      between those in mountain areas and those in urban settings. CONCLUSIONS:
      Mountain rescue teams should be prepared to manage MCIs. Knowledge should be
      reviewed and training performed regularly. Cooperation between terrestrial rescue
      services, avalanche safety authorities, and helicopter crews is critical to
      successful management of MCIs in mountain areas.

PMID- 29446651
TI  - Mild traumatic brain injury: evaluation of olfactory dysfunction and clinical
      neurological characteristics.
AB  - OBJECTIVE: To evaluate olfactory function and clinical-neurological
      characteristics in a group of patients with mild head trauma. METHODS: A total of
      352 patients with MTBI underwent olfactory function evaluation. The site of head
      trauma, loss of consciousness <20 min, memory loss, subjective presence or
      absence of olfaction and other clinical, neurological and radiological aspects
      were evaluated and compared with the olfactory dysfunction. RESULTS: A total of
      33.5% patients enrolled in the study had an olfactory dysfunction. Eighty-seven
      percent of the patients had a diagnosis of anosmia whereas 13% had a diagnosis of
      hyposmia. Statistical analysis did not show a correlation between radiologically
      detected head lesions and different types of olfactory dysfunction (p > 0.05).
      Besides, no difference between head lesion site and different olfactory
      dysfunction was reported (p = 0.5). Regarding olfactory sub-tests a low detection
      threshold was present in these patients. CONCLUSION: The possibility of olfactory
      dysfunction should be considered in any case of MTBI appears differently than
      expected, a minor head injury causes anosmia much more frequently than hyposmia.

PMID- 29446652
TI  - Developmental regulation of the intestinal FGF19 system in domestic pigs.
AB  - Fibroblast growth factor-19 (FGF19) is an emerging endocrine factor involved in
      the regulation of bile acid homeostasis and energy metabolism in rodents and
      humans. In pigs, however, the FGF19 system remains largely unexplored. This study
      was designed to investigate the developmental regulation of the FGF19 system in
      domestic pigs. Samples of intestinal sections, liver, and plasma were collected
      from 24 pigs ( n = 6) at four developmental stages (birth, preweaning,
      postweaning, and adulthood). In the intestine, expression of the farnesoid X
      receptor (FXR) and FGF19 showed a congruent time- and region-dependent
      regulation, beginning soon after birth to achieve maximal expression in ileum
      during adulthood. The same temporal pattern was followed by the circulating
      concentration of FGF19, and these changes were accompanied by a time-related
      increase in the ileal proportion of bile acids that potently activate FXR.
      Conversely, genes belonging to the FGF19 signaling machinery achieved maximal
      expression in the small intestine at birth to decrease sharply afterward. In the
      liver, gene expression of FGF19 receptors and enzymes involved in bile acid
      biosynthesis paralleled after-birth changes in plasma concentration of this
      enterokine and attained a maximum during postweaning when plasma FGF19 was the
      lowest. Although detectable at birth, the hepatic expression of genes belonging
      to the bile acid-FXR-FGF19 pathway was low before the onset of enteral feeding.
      In summary, the porcine FGF19 system is present from birth, operative before the
      onset of enteral feeding, and regulated in a temporal and section-specific
      manner. NEW & NOTEWORTHY Fibroblast growth factor-19 (FGF19) is an emerging
      endocrine factor. The domestic pig is a translational model of value in
      biomedical research. We show for the first time that in pigs the intestinal FGF19
      system is present from birth, operative before the onset of enteral feeding, and
      regulated in a temporal and section-specific manner. This work identifies pigs as
      a suitable model for investigating the implications of FGF19 signaling within and
      beyond the gut-liver axis.

PMID- 29446654
TI  - Hypouricaemic effects of yoghurt containing Lactobacillus gasseri PA-3 in
      patients with hyperuricaemia and/or gout: A randomised, double-blind, placebo
      controlled study.
AB  - PURPOSE: Lactobacillus gasseri PA-3 (PA-3) has been previously shown to decrease
      serum uric acid (SUA) levels in subjects with increased SUA. In this study, we
      investigated whether PA-3 is also capable of decreasing SUA levels in patients
      with hyperuricaemia and/or gout. METHODS: Twenty-five patients with
      hyperuricaemia and/or gout completed this study. Urate-lowering drugs were
      discontinued for 12 weeks (week -4 to week 8). After flushing of urate-lowering
      drugs for 4 weeks (week 0), patients were randomised equally to receive diets
      containing yoghurt beverages with PA-3 or without PA-3 for a duration of 8 weeks
      (week 8). The intention to treat (ITT) population included all subjects who were
      randomised, and the per-protocol (PP) population included subjects who completed
      the experiment with compliance. We evaluated SUA levels at the end of the study
      as well as changes in SUA levels in comparison to week 0. RESULTS: In both ITT
      and PP analyses, there were no significant differences in SUA levels or in the
      changes in SUA levels compared to week 0 between the two groups. However, in a
      sub-population whose SUA levels at week 0 were within one SD of the mean of the
      whole PP population, changes in SUA levels in the group consuming PA-3-containing
      yoghurt were significantly lower than those of the control group (p = .0378).
      CONCLUSION: PA-3-containing yoghurt improves SUA levels, even in patients with
      hyperuricaemia and/or gout.

PMID- 29446653
TI  - cGAS-mediated autophagy protects the liver from ischemia-reperfusion injury
      independently of STING.
AB  - Liver ischemia-reperfusion (I/R) injury occurs through induction of oxidative
      stress and release of damage-associated molecular patterns (DAMPs), including
      cytosolic DNA released from dysfunctional mitochondria or from the nucleus.
      Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is
      a cytosolic DNA sensor known to trigger stimulator of interferon genes (STING)
      and downstream type 1 interferon (IFN-I) pathways, which are pivotal innate
      immune system responses to pathogen. However, little is known about the role of
      cGAS/STING in liver I/R injury. We subjected C57BL/6 (WT), cGAS knockout (cGAS-/
      ), and STING-deficient (STINGgt/gt) mice to warm liver I/R injury and that found
      cGAS-/- mice had significantly increased liver injury compared with WT or
      STINGgt/gt mice, suggesting a protective effect of cGAS independent of STING.
      Liver I/R upregulated cGAS in vivo and also in vitro in hepatocytes subjected to
      anoxia/reoxygenation (A/R). We confirmed a previously published finding that
      hepatocytes do not express STING under normoxic conditions or after A/R.
      Hepatocytes and liver from cGAS-/- mice had increased cell death and reduced
      induction of autophagy under hypoxic conditions as well as increased apoptosis.
      Protection could be restored in cGAS-/- hepatocytes by overexpression of cGAS or
      by pretreatment of mice with autophagy inducer rapamycin. Our findings indicate a
      novel protective role for cGAS in the regulation of autophagy during liver I/R
      injury that occurs independently of STING. NEW & NOTEWORTHY Our studies are the
      first to document the important role of cGAS in the acute setting of sterile
      injury induced by I/R. Specifically, we provide evidence that cGAS protects liver
      from I/R injury in a STING-independent manner.

PMID- 29446655
TI  - MicroRNAs as molecular targets of quercetin and its derivatives underlying their
      biological effects: A preclinical strategy.
AB  - Quercetin is a well-known flavonoid naturally occurring in most of the plant
      foods and is often found in the human diet. It can act as a potent antioxidant
      and anti-inflammatory agent, and plays significant roles in the prevention of
      various chronic diseases. Recent findings revealed that quercetin could affect
      metabolic traits by regulating certain transcription factors or key proteins
      involved in cellular signal pathways and influencing the expression of functional
      genes along with related regulatory pathway(s), and that microRNAs (miRNAs)
      circulate in body fluids and are involved in post-transcriptional gene silencing
      and regulation of gene expression in various biological processes including
      development, proliferation, metabolism and inflammation. This article reviews the
      studies into the molecular pathways underlying the beneficial bioactivities of
      quercetin and its derivatives, and the modulatory effects of miRNAs by quercetin
      and its derivatives on miRNAs-mediated cellular processes. MicroRNAs as molecular
      targets of quercetin and its derivatives and as predictive biomarkers for early
      diagnosis of the outcome of quercetin-rich diets are highlighted. Current
      limitations and future directions of research on the impact and associated
      mechanism(s) of the synergies between quercetin species and other co-existing
      nutrients/bioactives on the expression of miRNAs as well as the roles of miRNAs
      in overall nutritional control are critically discussed.

PMID- 29446656
TI  - Crohn's Disease Candidate Gene Alleles Predict Time to Progression from
      Inflammatory B1 to Stricturing B2, or Penetrating B3 Phenotype.
AB  - AIM: Crohn's disease (CD) patients are mostly diagnosed with the uncomplicated
      inflammatory form of disease; however, the majority will progress to complicated
      stricturing or penetrating disease over time. It is important to identify
      patients at risk for disease progression at an early stage. The aim of our study
      was to examine the role of 33 candidate CD genes as possible predictors of
      disease progression and their influence on time to progression from an
      inflammatory to a stricturing or penetrating phenotype. METHODS: Patients with an
      inflammatory phenotype at diagnosis were followed for 10 years and 33 CD
      associated polymorphisms were genotyped. To test for association with CD, 449
      healthy individuals were analyzed as the control group. RESULTS: Ten years after
      diagnosis, 39.1% of patients had not progressed beyond an inflammatory phenotype,
      but 60.9% had progressed to complicated disease, with average time to progression
      being 5.91 years. Association analyses of selected single nucleotide
      polymorphisms (SNPs) confirmed associations with CD for 12 SNPs. Furthermore,
      seven loci were associated with disease progression, out of which SNP rs4263839
      in the gene TNFSF15 showed the strongest association with disease progression and
      the frameshift mutation rs2066847 in the gene NOD2 showed the strongest
      association with time to progression. CONCLUSIONS: The results of our study
      identified specific genetic biomarkers as useful predictors of both disease
      progression and speed of disease progression in patients with CD.

PMID- 29446657
TI  - Health Risks among People with Severe Mental Illness in Psychiatric Outpatient
      Settings.
AB  - Life expectancy is greatly reduced in patients with schizophrenia, and
      cardiovascular diseases are a leading cause of mortality. The aim of this cross
      sectional study was to investigate the prevalence of overweight, obesity, and
      cardiovascular disease (CVD) risk and to investigate the relationships between
      self-rated health, sense of coherence, CVD risk, and body mass index (BMI) among
      people with severe mental illness (SMI) in psychiatric outpatient settings.
      Nearly 50% of the participants were exposed to moderate/high risk of CVD and over
      50% were obese. The results showed no statistically relationships between the
      subjective and objective measures (Bayes factor <1) of health. The integration of
      physical health into clinical psychiatric nursing practice is vital.

PMID- 29446658
TI  - Post-concussive symptoms after a mild traumatic brain injury during childhood and
      adolescence.
AB  - OBJECTIVE: Mild traumatic brain injury (mTBI) is common injury during childhood
      and adolescence but the long-term outcomes are poorly understood. This study
      examined post-concussive symptoms and behavioural outcomes in children and
      adolescents up to 24 months post-mTBI. METHOD: Parents of children aged 8-15
      years with mTBI completed the BASC-2 and Rivermead Post-Concussion Symptoms
      Questionnaire at baseline, 1-, 6-, 12- and 24 months post-injury. An age-matched
      traumatic brain injury-free cohort was recruited and assessed at 12- and 24
      months. RESULTS: PCSs decreased significantly over the first 12 months post
      injury. At 12- and 24 months post-injury, the mTBI group reported more PCSs and
      behavioural symptoms compared to controls. Parents of children with mTBI were
      more likely to report >=4 problematic PCS symptoms (28% at both time points)
      compared to controls (7.7% and 1.7% at 12 and 24 months, respectively). The mTBI
      group was 4.63 times more likely to have four or more ongoing PCS symptoms at 12
      months post-injury compared to controls. Headache was the most common acute post
      injury symptom (55%), while the most commonly reported persistent symptoms were
      irritability, frustration, forgetfulness and fatigue. CONCLUSIONS: PCSs are
      common 2 years post-mTBI in childhood or adolescence. Given this, additional
      intervention and support is needed for families post-injury.

PMID- 29446659
TI  - Association Analysis of the Brain-Derived Neurotrophic Factor Gene Val66Met
      Polymorphism and Gender with Efficacy of Antidepressants in the Chinese Han
      Population with Generalized Anxiety Disorder.
AB  - BACKGROUND AND AIM: This study was designed to explore the relationship between
      the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and
      antidepressants' efficacy in the Chinese Han population with generalized anxiety
      disorder (GAD). MATERIALS AND METHODS: We recruited 206 patients who met the
      diagnostic criteria for GAD into the test group, and assigned 209 healthy
      participants to the control group. All participants were genotyped for the BDNF
      Val66Met polymorphism. GAD patients were treated with escitalopram or extended
      release venlafaxine. We used the Hamilton Rating Scale for Anxiety (HAM-A) to
      assess the response to 8-weeks of antidepressant treatment for GAD. RESULTS: We
      did not identify any significant differences in the allelic or genotype
      frequencies of the BDNF Val66Met polymorphism between the test and control group.
      Furthermore, we did not detect any significant difference in the allele or
      genotype frequency of BDNF Val66Met between patients with different treatment
      responses. Finally, we did not detect any significant difference in the HAM-A
      score reduction rate among patients with different genotypes, gender, or
      treatment drugs. CONCLUSIONS: No significant difference was found in the BDNF
      Val66Met polymorphism between patients with GAD and healthy controls, nor was
      this polymorphism significantly associated with antidepressant drug efficacy for
      GAD.

PMID- 29446660
TI  - The role of the daily feeding rhythm in the regulation of the day/night rhythm in
      triglyceride secretion in rats.
AB  - Plasma triglyceride (TG) levels show a clear daily rhythm, however, thus far it
      is still unknown whether this rhythm results from a daily rhythm in TG
      production, TG uptake or both. Previous studies have shown that feeding activity
      affects plasma TG concentrations, but it is not clear how the daily rhythm in
      feeding activity affects plasma TG concentrations. In the present study, we
      measured plasma TG concentrations and TG secretion rates in rats at 6 Zeitgeber
      times to investigate whether plasma TG concentrations and TG secretion show a
      daily rhythm. We found that plasma TG concentrations and TG secretion show a
      significant day/night rhythm. Next, we removed the daily rhythm in feeding
      behavior by introducing a 6-meals-a-day (6M) feeding schedule to investigate
      whether the daily rhythm in feeding behavior is necessary to maintain the daily
      rhythm in TG secretion. We found that the day/night rhythm in TG secretion was
      abolished under 6M feeding conditions. Hepatic apolipoprotein B (ApoB) and
      microsomal TG transfer protein (Mttp), which are both involved in TG secretion,
      also lost their daily rhythmicity under 6M feeding conditions. Together, these
      results indicate that: (1) the daily rhythm in TG secretion contributes to the
      formation of a day/night rhythm in plasma TG levels and (2) a daily feeding
      rhythm is essential for maintaining the daily rhythm in TG secretion.

PMID- 29446661
TI  - Stigma and Spiritual Well-being among People Living with HIV/AIDS in Southern
      Appalachia.
AB  - The Appalachian South is disproportionately affected by HIV/AIDS. Partly due to
      the negative connotation that this disease carries in religiously conservative
      areas, HIV-related stigma remains a critical barrier to HIV care in the South.
      However, spirituality is a well-documented, effective coping mechanism among
      persons living with HIV/AIDS (PLWH). The purpose of this study was to examine the
      relationship between HIV-related stigma and spiritual well-being among a sample
      of PLWH (n = 216) in Appalachian counties of Tennessee and Alabama using the HIV
      Stigma Scale and the Spiritual Well-being Scale. Overall, disclosure of HIV
      status was the most highly reported stigma concern. Women reported higher levels
      of stigma and religious well-being than men. While existential well-being was
      negatively correlated with stigma, no significant overall correlation was found
      between religious well-being and stigma. Our findings reveal the importance of
      defining theology and differentiating between cultural religious conditioning and
      internalized beliefs.

PMID- 29446662
TI  - Parents' Knowledge and Beliefs about the Impact of Exposure to Media Violence on
      Children's Aggression.
AB  - The current study aimed to assess Jordanian parents' knowledge and beliefs about
      the effects of violent media on children's aggressive behavior. A sample of 262
      parents of children aged 6-11 years completed a Media Quotient questionnaire
      about children's media habits, media effects, and children's aggressive behavior.
      Parents reported that their children spend an average of 4.83 h (SD = 2.12)
      watching TV, 3.20 h (SD = 2.29) playing video games, 1.07 h (SD = 0.88) listening
      to music, and only 0.52 min (SD = 0.67) reading for pleasure per day. Parents
      have a moderate level of knowledge about the media effect (M = 15.49, SD =
      3.439). Children of parents who have adequate knowledge about the media effect,
      spend less time watching TV (r = -.355, p < .001), playing video games (r = 
      .265, p < .001), and listening to music (r = -.347, p < .001). Ninety-two percent
      (n = 241) of parents were concerned about the amount of sexual and of violent
      content their children see in movies or on TV. Children who spend more time
      playing video games (r = -.201, p = .004) show aggressive relational behavior.
      This study suggests that increasing parents' knowledge of media of evidence-based
      programs may have a protective effect on children's behavior.

PMID- 29446663
TI  - Editor's presentation.

PMID- 29446666
TI  - The Impact of Climate Change on Raw and Untreated Wastewater Use for Agriculture,
      Especially in Arid Regions: A Review.
AB  - Climate change is one of the major challenges of our time that pose unprecedented
      stress to the environment and threats to human health. The global impacts of
      climate change are vast, spanning from extreme weather events to changes in
      patterns and distribution of infectious diseases. Lack of rainfall associated
      with higher temperatures has a direct influence on agricultural production. This
      is compounded by a growing population forecasted to expand further with
      increasing needs for food and water. All this has led to the increasing use of
      wastewater worldwide. In this review, we more specifically discuss the use of
      untreated wastewater in agriculture in the Middle East and North Africa (MENA)
      countries, the most arid region in the world. This presents challenges for
      agriculture with respect to water availability and increasing wastewater use in
      agri-food chain. This in turn exerts pressures on the safety of food raised from
      such irrigated crops. Current practices in the MENA region indicate that
      ineffective water resource management, lack of water quality policies, and slow
      paced wastewater management strategies continue to contribute to a decline in
      water resources and an increased unplanned use of black and graywater in
      agriculture. Radical actions are needed in the region to improve water and
      wastewater management to adapt to these impacts. In this regard, the 2006 WHO
      guidelines for the use of wastewater contain recommendations for the most
      effective solutions. They provide a step-by-step guide for series of appropriate
      health protection measures for microbial reduction targets of 6 log units for
      viral, bacterial, and protozoan pathogens, but these need to be combined with new
      varieties of crops that are drought and pest resistant. More research into
      economic local treatment procedures for wastewater in the region is warranted.

PMID- 29446667
TI  - Safety of Administering Furosemide During Nuclear Diuretic Renography in Patients
      With Sulfonamide Allergies.
AB  - OBJECTIVE: We reviewed the safety of nuclear diuretic renography with furosemide
      in patients with sulfonamide allergies. The electronic health record was used to
      uncover any drug effects reported within 30 days of diuretic renograms performed
      between January 2009 and December 2015. CONCLUSION: Eighty-three of 1103 (7.5%)
      diuretic renograms were performed on patients with sulfonamide allergies. Two
      instances of minor rash occurred. No serious reactions occurred. Furosemide is
      associated with an extremely low risk of minor reactions in patients with
      sulfonamide allergies.

PMID- 29446668
TI  - Improved Opacification of a Suboptimally Enhanced Pulmonary Artery in Chest CT:
      Experience Using a Dual-Layer Detector Spectral CT.
AB  - OBJECTIVE: The objective of our study was to evaluate the quality of virtual
      monoenergetic imaging (VMI) from dual-layer detector spectral CT and the effect
      of virtual monoenergetic images obtained at low energies on the detection of
      pulmonary embolism (PE) in patients with a suboptimally enhanced pulmonary artery
      on chest CT. MATERIALS AND METHODS: Of 1552 consecutive chest CT examinations
      performed with dual-layer detector spectral CT using a routine protocol with a
      tube voltage of 120 kVp, 79 examinations with suboptimal enhancement of the
      pulmonary artery (i.e., mean attenuation of pulmonary artery <= 180 HU) were
      included. The mean attenuation of the pulmonary artery, noise, contrast-to-noise
      ratio (CNR), and signal-to-noise ratio (SNR) of virtual monoenergetic images
      obtained at 40-200 keV were compared with those of the conventional 120-kVp
      images. The virtual monoenergetic images with the best CNR were compared with the
      120-kVp images with regard to subjective image quality and diagnostic accuracy
      for detecting PE. RESULTS: Sufficient attenuation of the pulmonary artery (> 180
      HU) was obtained using VMI for 78 of the 79 examinations. The noise levels of the
      virtual monoenergetic images were gradually increased with decreasing energy
      level (i.e., kiloelectron volt setting). The CNR and SNR of virtual monoenergetic
      images at 40-65 keV were significantly higher (both, p < 0.001) than the CNR and
      SNR of the 120-kVp images. The CNR was the highest at 40 keV for all cases.
      Diagnostic accuracy for detecting PE was significantly higher for 40-keV images
      (reader 1: AUC = 0.992, p = 0.033; reader 2: AUC = 0.986, p = 0.043) than for 120
      kVp images (reader 1, AUC = 0.911; reader 2, AUC = 0.933). The subjective quality
      was not different between these two images. CONCLUSION: In chest CT examinations
      in which the pulmonary artery is suboptimally enhanced, obtaining virtual
      monoenergetic images at a low energy setting using dual-layer detector spectral
      CT allows sufficient attenuation of the pulmonary artery to be achieved while
      preserving image quality and increasing diagnostic performance for detecting PE.

PMID- 29446669
TI  - Segmental Arterial Mediolysis: Abdominal Imaging of and Disease Course in 111
      Patients.
AB  - OBJECTIVE: The purpose of this study is to identify the imaging characteristics
      of segmental arterial mediolysis (SAM) at presentation and establish the
      longitudinal course of disease. MATERIALS AND METHODS: We retrospectively
      identified patients with SAM at a single institution from 2000 through 2015.
      Diagnosis was based on published guidelines with multidisciplinary consensus.
      Imaging studies obtained at initial evaluation were reviewed to evaluate imaging
      findings and vascular territory distribution. All subsequent follow-up imaging
      studies were reviewed to assess for progression, stability, or regression.
      RESULTS: We identified 111 patients (79 men and 32 women; median age, 51 years)
      who met the diagnostic criteria for SAM. Abdominal pain was the most common
      presentation (74%), followed by flank pain (21%). SAM most commonly affected the
      renal arteries (47%), superior mesenteric artery (46%), celiac trunk (46%),
      hepatic artery (23%), iliac arteries (18%), and splenic artery (14%). The most
      common imaging findings were dissection (86%), aneurysm (57%), beading or webs
      (28%), occlusion (19%), and a rind or wall thickening (15%). The 247 available
      follow-up imaging studies for 97 patients (median follow-up, 12 months) showed
      progression in 19 patients (20%), with either stability or regression observed in
      the remaining patients. CONCLUSION: SAM most commonly affects the renal arteries,
      superior mesenteric artery, and celiac artery. Dissections and aneurysms are the
      most common imaging findings. Follow-up imaging studies show stability or
      regression in most patients.

PMID- 29446670
TI  - Diagnostic Performance of Margin Features in Thyroid Nodules in Prediction of
      Malignancy.
AB  - OBJECTIVE: The purpose of this study was to evaluate thyroid nodule margins for
      specific morphologic features and determine the diagnostic performance of these
      features in differentiating papillary carcinoma from benign thyroid nodules.
      MATERIALS AND METHODS: Nodules measuring 1-3 cm in largest diameter that had been
      evaluated with high-resolution ultrasound (12-18 MHz) and ultrasound-guided
      biopsy with definitive pathologic diagnosis were analyzed. Three blinded board
      certified readers evaluated high-resolution images of each nodule for jagged
      edges, lobulated borders, and curved borders along their margins. Reader
      interpretations were correlated with the pathologic diagnosis to determine the
      diagnostic performance of each feature. A board-certified pathologist analyzed 10
      randomly selected nodules with jagged edges by slide review to evaluate for
      structural correlation with the imaging finding. RESULTS: The diagnostic
      performance of jagged edges in papillary carcinoma of the thyroid was 67.4%
      sensitive and 78.3% specific (odds ratio, 7.44; p < 0.001) for malignancy. Jagged
      edges correlated with infiltrative variant expansion at slide review. Lobulated
      borders had sensitivity of 76.1% and specificity of 60.9% for papillary carcinoma
      (odds ratio, 4.95; p = 0.001) for malignancy. Curved borders were not a
      significant predictor of papillary carcinoma. CONCLUSION: Jagged edges and
      lobulated borders of thyroid nodule margins are statistically significant
      predictors of papillary carcinoma of the thyroid. Jagged edges correlate with
      infiltrative-type expansion and may be useful predictors of more aggressive
      papillary carcinomas.

PMID- 29446671
TI  - Unenhanced MRI as an Alternative to 99mTc-Labeled Dimercaptosuccinic Acid
      Scintigraphy in the Detection of Pediatric Renal Scarring.
AB  - OBJECTIVE: The purpose of this study was to determine whether unenhanced MRI
      without sedation is a feasible substitute for dimercaptosuccinic acid (DMSA)
      scintigraphy in the detection of renal scars in pediatric patients. SUBJECTS AND
      METHODS: Patients scheduled for 99mTc-labeled DMSA scintigraphy for assessment of
      possible renal scars were recruited to undergo unenhanced MRI (free-breathing fat
      suppressed T2-weighted single-shot turbo spin-echo and T1-weighted gradient-echo
      imaging, 13 minutes' total imaging time). Scintigraphic and MRI studies were
      evaluated by two independent blinded specialty-based radiologists. For each
      imaging examination, readers identified scars in upper, middle, and lower kidney
      zones and rated their diagnostic confidence and the quality of each study. The
      scintigraphic readers' consensus score opinion for the presence of scars was
      considered the reference standard. RESULTS: DMSA scintigraphy showed scarring in
      19 of the 78 (24.4%) evaluated zones and MRI in 18 of the 78 (23.1%). The two MRI
      readers found mean sensitivities of 94.7% and 89.5%, identical specificities of
      100%, and diagnostic accuracies of 98.7% and 97.4%. Interobserver agreement was
      98.7% for MRI and 92.3% for DMSA scintigraphy. The MRI readers were significantly
      more confident in determining the absence rather than the presence of scars (p =
      0.02). MRI readers were more likely to rate study quality as excellent (84.6%)
      than were the scintigraphic readers (57.7%) (p = 0.024). CONCLUSION: Unenhanced
      MRI has excellent sensitivity, specificity, diagnostic accuracy, and
      interobserver agreement for detecting renal scars in older children who do not
      need sedation. It may serve as a substitute modality, especially when DMSA is not
      available.

PMID- 29446672
TI  - Choledochal Malformations: Surgical Implications of Radiologic Findings.
AB  - OBJECTIVE: The purpose of this article is to review the relevant pathophysiologic
      features, appearances, and surgical implications of choledochal malformations.
      CONCLUSION: Choledochal malformations, colloquially called choledochal cysts,
      initially described in 1723, have been recategorized multiple times, the most
      widely accepted being the Todani classification based on morphologic features and
      location. Although readily applied to imaging findings, this classification
      system does not correlate well with clinical and surgical management. In 2004,
      Visser and colleagues proposed an alternative that emphasized the etiologic
      factors, imaging appearance, and treatment approach.

PMID- 29446673
TI  - A Systematic Review of Fatigue in Radiology: Is It a Problem?
AB  - OBJECTIVE: The purpose of this study was to review current literature regarding
      radiologist fatigue. MATERIALS AND METHODS: A literature search was performed
      using PubMed. Key words and Medical Subject Heading terms were used to generate
      refined queries with inclusion and exclusion criteria, focusing on fatigue and
      error. Results were selected according to these criteria: examined radiologist
      fatigue and radiologic error stemming from fatigue; experimental results measured
      as accuracy, error, or performance; and peer-reviewed publication. The risk of
      bias was addressed by including both quantitative and qualitative studies.
      RESULTS: Twenty-seven articles were included, mainly primary research articles.
      Common outcome measures included subjective self-reports and tests to measure
      eyestrain. Reaction time was also recorded, accounting for variables such as age
      and experience. One group recommended that guidelines should be implemented
      regarding number of hours worked. Most recommended ergonomic interventions,
      proposing the implementation of tools to measure and standardize fatigue and
      optimize workflow, in conjunction with considering radiologists individually.
      Education in appropriate viewing habits and breaks were also suggested. Only one
      study with seven participants recommended that radiologists should sleep well to
      improve their performance and overall well-being, despite the undeniable evidence
      that radiologists are fatigued. CONCLUSION: Fatigue is present in radiology and
      affects diagnostic accuracy.

PMID- 29446674
TI  - Intravoxel Incoherent Motion MRI of Rectal Cancer: Correlation of Diffusion and
      Perfusion Characteristics With Prognostic Tumor Markers.
AB  - OBJECTIVE: The objective of our study was to evaluate the intravoxel incoherent
      motion (IVIM)-DWI derived parameters and their relationships with tumor
      prognostic markers using 3-T MRI in patients with rectal cancer. SUBJECTS AND
      METHODS: Fifty-two patients with histopathologically proven rectal cancer who
      underwent preoperative pelvic MRI were prospectively enrolled in this study.
      Diffusion and perfusion parameters including the apparent diffusion coefficient
      (ADC), pure diffusion coefficient, perfusion fraction, and pseudodiffusion
      coefficient derived from IVIMDWI were independently measured by two radiologists.
      Comparisons of IVIM-DWI-derived parameters in patients with different tumor
      prognostic markers were made using the independent-samples t test, ANOVA, and
      Mann-Whitney U test. The correlations between IVIM-DWI-derived parameters and
      tumor grade and tumor stage were further evaluated using Spearman correlation
      analysis. Interobserver agreement was evaluated using the intraclass correlation
      coefficient (ICC). RESULTS: Excellent interobserver reproducibility was obtained
      for the IVIM-DWI-derived parameters (range of ICCs with 95% limits of agreement =
      0.9309-0.9948, which is narrow). ADC, pseudodiffusion coefficient, and perfusion
      fraction tended to rise with greater tumor differentiation (r = 0.520, p < 0.001;
      r = 0.447, p = 0.001; r = 0.354, p = 0.010, respectively). The pure diffusion
      coefficient and pseudodiffusion coefficient showed a trend of decreasing with
      increasing tumor stages (r = 0.479, p < 0.001; r = 0.517, p < 0.001). The group
      of patients with extramural vascular invasion (EMVI) showed lower pseudodiffusion
      coefficient values than the group of patients with no EMVI (p < 0.05).
      CONCLUSION: IVIM-DWI-derived parameters in patients with rectal cancer,
      especially the pseudodiffusion coefficient, are associated with tumor grade and
      tumor stage and show statistically significant differences between subjects with
      EMVI and those without EMVI. IVIM-DWI-derived parameters would be helpful in
      predicting tumor aggressiveness and prognosis.

PMID- 29446675
TI  - Colorectal Liver Metastasis: Overview of Treatment Paradigm Highlighting the Role
      of Ablation.
AB  - OBJECTIVE: The objective of this article is to discuss the current treatment
      options for colorectal cancer (CRC) liver metastases and the role of ablation.
      CONCLUSION: A randomized control trial of ablation combined with chemotherapy
      showed improved overall survival compared with chemotherapy alone. Local
      recurrence rates are comparable to those associated with resection when ablative
      margins of more than 5 mm are achieved and target lesions are smaller than 3 cm.
      In patients with unresectable disease, ablation for curative intent should be
      considered.

PMID- 29446676
TI  - Advanced DWI Methods for the Assessment of Ischemic Stroke.
AB  - OBJECTIVE: This commentary discusses recent preclinical research on the potential
      feasibility and benefits of applying advanced DWI methods for the assessment of
      acute stroke. CONCLUSION: A DWI parameter known as kurtosis shows promise in
      helping to identify tissue that is likely salvageable at reperfusion.

PMID- 29446677
TI  - How to Integrate Cell-Free DNA Screening With Sonographic Markers for Aneuploidy:
      An Update.
AB  - OBJECTIVE: The sonologist detects a so-called "soft marker" during approximately
      10% of routine second-trimester anatomy examinations and is often uncertain about
      what further management is appropriate. This article will specifically address
      the management of patients with sonographic markers for six common entities:
      choroid plexus cysts (CPCs), ventriculomegaly (VM), echogenic intracardiac focus
      (EIF), urinary tract dilation (UTD), fetal echogenic bowel (FEB), and femoral and
      humeral shortening. The use of cell-free DNA screening and its relationship to
      these sonographic findings will be reviewed. CONCLUSION: The era of ultrasound
      markers as a screen for fetal aneuploidy is coming to a close. The detection of
      these markers on an ultrasound examination should simply serve as a reminder to
      ensure that the patient was offered cell-free DNA screening or conventional
      analyte screening. Cell-free DNA testing is revolutionizing screening. With
      normal results on a cell-free DNA test, many isolated soft markers-including
      CPCs, EIF, mild rhizomelic limb shortening, and mild pyelectasis-are irrelevant
      from a genetic standpoint. However, further counseling and workup are indicated
      for VM, true FEB, femur or humerus length measurement that is less than 2.5
      percentile value, and pyelectasis to evaluate for the nongenetic associations
      with these findings. Finally, cell-free DNA testing is currently a screening
      test; positive results require definitive diagnostic testing with amniocentesis
      or chorionic villus sampling.

PMID- 29446678
TI  - Interrater Agreement and Diagnostic Accuracy of a Novel Computer-Aided Detection
      Process for the Detection and Prevention of Retained Surgical Instruments.
AB  - OBJECTIVE: The purpose of this study is to evaluate the diagnostic accuracy of a
      process incorporating computer-aided detection (CAD) for the detection and
      prevention of retained surgical instruments using a novel nondeformable
      radiopaque MUTag. MATERIALS AND METHODS: A high-specificity CAD system was
      developed iteratively from a training set (n = 540 radiographs) and a validation
      set (n = 560 radiographs). A novel test set composed of 700 thoracoabdominal
      radiographs (410 with a randomly placed MUTag and 290 without a MUTag) was
      obtained from 10 cadavers embedded with confounding iatrogenic objects. Data were
      analyzed first by the blinded CAD system; radiographs coded as negative (n = 373)
      were then independently reviewed by five blinded radiologists. The reference
      standard was the presence of a MUTag. Sensitivity and specificity were
      calculated. Interrater agreement was assessed with Cohen kappa values. Mean (+/-
      SD) image analysis times were calculated. RESULTS: The high-specificity CAD
      system had one false-positive (sensitivity, 79.5% [326/410]; specificity, 99.7%
      [289/290]). A combination of the CAD system and one failsafe radiologist had
      superior sensitivity (98.5% [404/410] to 100% [410/410]) and specificity (99.0%
      [287/290] to 99.7% [289/290]), with 327 (47%) radiographs not requiring immediate
      radiologist review. Interrater agreement was almost perfect for all radiologist
      pairwise comparisons (kappa = 0.921-0.992). Cumulative mean image analysis time
      was less than one minute (CAD, 29 +/- 2 seconds; radiologists, 26 +/- 16
      seconds). CONCLUSION: The combination of a high-specificity CAD system with a
      failsafe radiologist had excellent diagnostic accuracy in the rapid detection of
      a nondeformable radiopaque MUTag.

PMID- 29446679
TI  - VIDEO: Technique to Restrict the Gore Viatorr Stent-Graft for TIPS Reduction.
AB  - OBJECTIVE: The Viatorr stent-graft (W. L. Gore and Associates), specifically made
      for transjugular intrahepatic portosystemic shunt (TIPS) creation, has
      significantly improved TIPS patency compared with bare metal stents. Post-TIPS
      hepatic encephalopathy (HE), however, remains relatively common after TIPS
      creation. We describe a technique to secondarily restrict a Viatorr stent-graft
      to treat post-TIPS refractory HE and maintain use of the Viatorr device.
      CONCLUSION: We show a simple technique to modify the Viatorr stent-graft for TIPS
      reduction.

PMID- 29446680
TI  - Initial Clinical Experience With an Inducible Magnetic Seed System for
      Preoperative Breast Lesion Localization.
AB  - OBJECTIVE: The purpose of this study is to evaluate a nonradioactive inducible
      magnetic seed system (Magseed, Endomag) for preoperative localization of
      nonpalpable breast lesions. CONCLUSION: All of the 73 seeds placed in the first 4
      months of clinical use were successfully placed and all were successfully
      retrieved intraoperatively. The mean time from seed placement to surgery was 3
      days. Early clinical experience suggests that Magseed is an effective and
      accurate means of preoperative breast lesion localization.

PMID- 29446681
TI  - Coronary CT Angiography: Use in Patients With Chest Pain Presenting to Emergency
      Departments.
AB  - OBJECTIVE: Previously published reports have shown that coronary CT angiography
      (CCTA) is a more efficient method of diagnosis than myocardial perfusion imaging
      (MPI) and stress echocardiography for patients presenting to emergency
      departments (EDs) with acute chest pain. In light of this evidence, the objective
      of this study was to examine recent trends in the use of these techniques in EDs.
      MATERIALS AND METHODS: The nationwide Medicare Part B databases for 2006-2015
      were the data source. The Current Procedural Terminology, version 4, codes for
      CCTA, MPI, and stress echocardiography were selected. Medicare place-of-service
      codes were used to determine procedure volumes in EDs. Medicare specialty codes
      were used to ascertain how many of these examinations were interpreted by
      radiologists, cardiologists, and other physicians as a group. RESULTS: From 2006
      to 2015, there was essentially no change in the number of MPI examinations
      performed in EDs for patients using Medicare (22,342 in 2006, 22,338 in 2015) or
      in the number of stress echocardiograms (3544 in 2006, 3520 in 2015). By
      contrast, the number of CCTA examinations increased rapidly, from 126 in 2006 to
      1919 in 2015 (compound annual growth rate, 35%). Despite this rapid growth,
      patients in EDs underwent 11.6 times as many MPI as CCTA examinations in 2015. In
      that last year of the study, radiologists interpreted 78% of ED MPI and 83% of ED
      CCTA examinations. CONCLUSION: Use of CCTA in EDs has increased rapidly, but far
      more MPI examinations are still being performed. This finding suggests that
      recently acquired evidence is not yet being fully acted upon.

PMID- 29446682
TI  - Fetal Urinary Tract Anomalies: Review of Pathophysiology, Imaging, and
      Management.
AB  - OBJECTIVE: Common fetal anomalies of the kidneys and urinary tract encompass a
      complex spectrum of abnormalities that can be detected prenatally by ultrasound.
      Common fetal anomalies of the kidneys and urinary tract can affect amniotic fluid
      volume production with the development of oligohydramnios or anhydramnios,
      resulting in fetal pulmonary hypoplasia and, potentially, abnormal development of
      other fetal structures. CONCLUSION: We provide an overview of common fetal
      anomalies of the kidneys and urinary tract with an emphasis on sonographic
      patterns as well as pathologic and postnatal correlation, along with brief
      recommendations for postnatal management. Of note, we render an updated
      classification of fetal abnormalities of the kidneys and urinary tract based on
      the presence or absence of associated urinary tract dilation. In addition, we
      review the 2014 classification of urinary tract dilation based on the Linthicum
      multidisciplinary consensus panel.

PMID- 29446683
TI  - Three-Dimensional Radial VIBE Sequence for Contrast-Enhanced Brain Imaging: An
      Alternative for Reducing Motion Artifacts in Restless Children.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of radially
      sampled 3D fat-suppressed T1-weighted gradient-echo sequences (radial volumetric
      interpolated breath-hold examination [radial VIBE]) for contrast-enhanced brain
      MRI of children through comparison with a magnetization-prepared rapid
      acquisition gradient-echo (MP-RAGE) sequence. MATERIALS AND METHODS: Sixty-five
      consecutive contrast-enhanced brain MRI examinations performed with axial MP-RAGE
      and radial VIBE sequences were included. For quantitative analysis, coefficients
      of variation of gray matter and white matter and CSF and relative contrast
      between tissue types (gray matter and white matter, gray matter and CSF, and
      white matter and CSF) for each sequence were calculated. For qualitative
      assessment, motion, pulsation artifacts, overall image quality, and lesion
      conspicuity were retrospectively scored on a 5-point scale. Quantitative and
      qualitative subgroup analyses were performed for patients with serious motion
      artifacts. RESULTS: Images obtained with the radial VIBE sequence had fewer
      motion and pulsation artifacts than those obtained with the MP-RAGE sequence (MP
      RAGE vs radial VIBE motion score, 3.57 +/- 1.00 vs 4.52 +/- 0.51; pulsation
      score, 3.57 +/- 0.60 vs 4.91 +/- 0.21; all p < 0.001). Among 25 images with
      serious motion artifacts, radial VIBE images had significantly higher scores for
      all qualitative parameters, including overall image quality, than did MP-RAGE
      images (overall image quality for MP-RAGE vs radial VIBE, 2.63 +/- 0.82 vs 3.42
      +/- 0.55, p < 0.001). CONCLUSION: The study showed that a radial fat-suppressed
      T1-weighted gradient-echo sequence is a viable alternative to conventional
      cartesian acquisition for contrast-enhanced brain imaging of restless children.

PMID- 29446684
TI  - Acute Nonhemorrhagic Adrenal Infarction in Pregnancy: 10-Year MRI Incidence and
      Patient Outcomes at a Single Institution.
AB  - OBJECTIVE: The purpose of this study was to retrospectively investigate the MRI
      incidence of nonhemorrhagic adrenal infarction in pregnant women undergoing MRI
      evaluation of acute abdominal or flank pain, assess the MRI features
      quantitatively, and report patient outcomes. MATERIALS AND METHODS: All abdominal
      MRI examinations of pregnant women with acute pain at one institution from May
      2005 to April 2015 were reviewed. The adrenals were evaluated for abnormal
      morphologic and signal intensity characteristics described in the literature
      characterizing nonhemorrhagic adrenal infarction and were compared with the
      contralateral adrenal by paired t tests. The findings were correlated with
      clinical presentation. Patient demographics and outcomes were gathered from the
      medical record. RESULTS: Findings of nonhemorrhagic adrenal infarction were
      present in 5 of 379 (1.3%) examinations of four pregnant patients (mean age, 28
      years; range, 20.8-33.9 years; mean gestational age, 26 weeks; range, 16-35
      weeks). MRI features included lengthening (mean, 39.8 versus 21.2 mm) (p = 0.005)
      and increased T2 signal intensity (p = 0.001) of the infarcted adrenal with
      surrounding edema and without T1 signal intensity suggesting hemorrhage. No
      alternative diagnosis was identified. All patients presented with severe acute
      abdominal or flank pain on the same side as the MRI findings, tenderness to
      palpation, and mild leukocytosis. All women delivered healthy infants.
      CONCLUSION: Unilateral nonhemorrhagic adrenal infarction was identified in 1.3%
      of abdominal MRI examinations performed for pregnant women with acute abdominal
      or flank pain. Knowledge of the MRI characteristics of this entity is important
      for recognizing it and may prevent further potentially invasive tests,
      procedures, or missed diagnoses.

PMID- 29446685
TI  - Inactivation of Salmonella and Surrogate Bacteria on Cashews and Macadamia Nuts
      Exposed to Commercial Propylene Oxide Processing Conditions.
AB  - Propylene oxide (PPO), a chemical fumigant, has been validated to reduce
      Salmonella on bulk almonds but has not been evaluated for other tree nuts. There
      is a need to identify nonpathogenic surrogate microorganisms whose inactivation
      is comparable to that of Salmonella to assure effective PPO processing parameters
      in different packaging configurations without introducing Salmonella into the
      pasteurization facility. The objective of this research was to compare the
      reduction of Salmonella and three potential surrogate bacterial strains,
      Enterococcus faecium ATCC 8459, Pediococcus acidilactici ATCC 8042, or
      Staphylococcus carnosus ATCC 51365, on cashews and macadamia nuts processed by
      using PPO. Whole cashews and macadamia nuts were coinoculated with a five-strain
      cocktail of Salmonella and one surrogate, dried to the original water activity of
      0.44 to 0.51 before being packaged in woven polypropylene bags (2.3 kg), and
      shipped overnight in Styrofoam containers under ambient conditions to a
      commercial facility for PPO treatment. Salmonella and surrogates were recovered
      by vigorous shaking in phosphate buffer (1:1, m/v), serial diluted, and plated
      onto tryptic soy agar with an overlay of xylose lysine Tergitol 4 for Salmonella
      or mannitol salt agar or bile esculin azide agar for each surrogate. The mean log
      reductions of Salmonella and each surrogate ( n = 18), within a sample and among
      all trials (three independent), were compared by using a matched pairs t test.
      Reduction in log CFU per gram of Salmonella was significantly greater than that
      of E. faecium on both macadamia nuts (7.3 +/- 0.19 versus 6.4 +/- 0.31) and
      cashews (5.4 +/- 0.15 versus 5.1 +/- 0.25) and significantly greater than P.
      acidilactici on both nuts (7.8 +/- 0.22 versus 6.3 +/- 0.33 on macadamia nuts and
      4.9 +/- 0.22 versus 4.1 +/- 0.25 on cashews). Reduction of S. carnosus exceeded
      that of Salmonella. E. faecium and P. acidilactici may be considered as
      surrogates for Salmonella on whole macadamia nuts and cashews processed by using
      PPO.

PMID- 29446686
TI  - Survey of Foodborne Pathogens, Aerobic Plate Counts, Total Coliform Counts, and
      Escherichia coli Counts in Leafy Greens, Sprouts, and Melons Marketed in the
      United States.
AB  - The objective of this research was to assess the microbiological status of leafy
      greens, sprouts, and melons from U.S. markets. A total of 14,183 samples of leafy
      greens, 2,652 samples of sprouts, and 3,411 samples of melons were collected
      throughout the United States from 2009 to 2014. The samples were analyzed for
      aerobic plate counts, total coliform counts, Escherichia coli counts, and the
      presence and levels of Salmonella, Shigella, Listeria monocytogenes, and Shiga
      toxin-producing E. coli (STEC), depending on the year and type of produce. Among
      the leafy greens, no E. coli O157:H7 or non-O157 STEC were detected from iceberg
      lettuce samples. The overall prevalences of Salmonella, E. coli O157:H7, non-O157
      STEC, and L. monocytogenes in the 14,183 samples of leafy greens were 0.05, 0.01,
      0.07, and 0.11%, respectively. Among sprout samples, no Salmonella or E. coli
      O157:H7 was detected, and the overall prevalences of non-O157 STEC and L.
      monocytogenes were 0.04 and 0.11%, respectively. Among melon samples, no
      Salmonella was detected from cucumbers, no L. monocytogenes was detected from
      cantaloupes, and the overall prevalences of Salmonella and L. monocytogenes were
      0.12 and 0.23%, respectively. L. monocytogenes levels were 0.4 to 1,470 most
      probable number (MPN)/g in leafy greens, 0.36 to 1,100 MPN/g in sprouts, and
      <0.03 to 150 MPN/g in melons, and most positive samples had low levels of these
      pathogens. The isolates from these foods were very diverse genetically. Foodborne
      pathogens, including Salmonella, STEC, and L. monocytogenes, had relatively low
      prevalences in the produce surveyed. Because these foods are usually consumed
      raw, measures should be taken to significantly minimize the presence and levels
      of human pathogens.

PMID- 29446687
TI  - icaA Gene of Staphylococcus aureus Responds to NaCl, Leading to Increased Biofilm
      Formation.
AB  - The objective of this study was to elucidate the role of the icaA gene in biofilm
      formation of Staphylococcus aureus exposed to NaCl. The icaA-deletion mutant of
      S. aureus ATCC 13565 was constructed with the temperature-sensitive plasmid
      pIMAY. Microtiter plate assays were performed to confirm biofilm formation for
      both the wild type and the mutant at 0% (control), 2, 4, and 6% NaCl. The
      microtiter plate assay revealed that biofilm formation by the wild type increased
      ( P < 0.05) as NaCl concentration increased, but biofilm formation of the mutant
      was not affected by NaCl concentration. Biofilm formation by the mutant was lower
      ( P < 0.05) than that by the wild type. These results indicate that icaA plays an
      important role in biofilm formation by S. aureus when the pathogen is exposed to
      NaCl.

PMID- 29446688
TI  - Chronic Thromboembolic Pulmonary Hypertension.

PMID- 29446689
TI  - Platelets and vascular integrity.
AB  - Platelets patrol the vasculature and adhere at sites of vascular damage after
      trauma to limit blood loss. In recent years, however, it has become clear that
      platelets also contribute to pathophysiologic processes such as thrombosis,
      atherosclerosis, stroke, sepsis and many more. An exciting new role for them is
      in non-classical hemostasis to prevent bleeding in the inflamed vasculature.
      Recent studies suggest that GPVI, CLEC-2, integrin alphaIIbbeta3 (GPIIb/IIIa),
      and the content of platelet alpha- and dense granules are important players in
      this process. This review summarizes the current knowledge about how platelets
      prevent vascular integrity during inflammation in the skin, lung, and the
      ischemic brain and their organ-specific role.

PMID- 29446690
TI  - Perineurial-like Cells and EMA Expression in the Suprachoroidal Region of the
      Human Eye.
AB  - The suprachoroidal region of the eye comprises vascular channels, melanocytes,
      and thin fibroblasts with elongated cytoplasm that are positioned directly
      adjacent to the densely collagenous sclera. Morphological similarities between
      these suprachoroidal fibroblasts and arachnoid cells and perineurial cells have
      been recognized, but whether these fibroblasts have a perineurial cell-like
      immunophenotype is not known. To further examine the relationship of these three
      cell types, we investigated the comparative expression of epithelial membrane
      antigen (EMA), the tight junction protein claudin-1, glucose transporter-1 (Glut
      1), and CD34 in suprachoroidal fibroblasts, arachnoid of the optic nerve sheath,
      and perineurium of ciliary nerves in eight human eye specimens. Granular,
      diffuse, and cytoplasmic EMA expression was seen in suprachoroidal fibroblasts,
      but this was not contiguous with the similar pattern of EMA expression in
      adjacent perineurium and arachnoid. CD34 expression in suprachoroidal fibroblasts
      was also seen, similar to arachnoid and perineurium. Claudin-1 and Glut-1 were
      not consistently expressed in suprachoroidal fibroblasts, distinguishing them
      from perineurial cells in particular and suggesting that these fibroblasts do not
      arise directly from adjacent arachnoid or perineurium. Nonetheless, the
      overlapping morphology and protein expression suggest phenotypic similarities in
      these cells that protect and support adjacent retina, optic nerve, and peripheral
      nerve.

PMID- 29446692
TI  - Can bracing help adults with chronic back pain and scoliosis? Short-term results
      from a pilot study.
AB  - BACKGROUND: Adult scoliosis is sometimes associated with back pain. Recently, the
      PeakTM Scoliosis Brace was designed to alleviate pain in adult patients with
      scoliosis. OBJECTIVES: To test the efficacy of the Peak Scoliosis Brace in
      reducing pain in adult scoliosis patients. STUDY DESIGN: Prospective experimental
      cohort study. METHODS: A total of 20 adult females with back pain secondary to
      idiopathic scoliosis were included. Patients were evaluated at baseline
      immediately before starting bracing and after 1 month. The brace had to be worn
      for at least 2 h per day. The outcome measures used were Graphical Rating Scale,
      Roland-Morris Questionnaire, Core Outcome Measurement Index, and Oswestry
      Disability Index. RESULTS: Worst pain, back pain, and leg pain significantly
      improved from 7.15 to 5.85, from 6.55 to 5.25, and from 5.65 to 3.55,
      respectively ( p < 0.05). A total of 75% of patients reported improved worst and
      leg pain, 65% improved back pain, 30% of patients achieved the minimal clinically
      significant difference of 2 points for worst pain, 60% for leg pain, and 25% for
      back pain. Roland-Morris Questionnaire and Core Outcome Measurement Index
      improved ( p < 0.05) and no differences were observed for Oswestry Disability
      Index. CONCLUSION: The Peak Scoliosis Brace led to some improvement of pain at 1
      month in a group of adult women with scoliosis and chronic low back pain. The
      quality of life did not change significantly. Clinical relevance According to our
      data, the Peak Brace is helpful to quickly improve pain in patients with chronic
      low back pain secondary to scoliosis. To achieve this goal, it should be applied
      for at least 2 h per day.

PMID- 29446691
TI  - Early insights into the characteristics and evolution of clinical parameters in a
      cohort of patients prescribed sacubitril/valsartan in Germany.
AB  - OBJECTIVES: This study aimed to provide early insights into sacubitril/valsartan
      (sac/val) prescription patterns and the demographic and clinical characteristics
      of patients prescribed sac/val in primary care and cardiology settings in
      Germany. METHODS: The study used electronic medical records from the German
      IMS(r) Disease Analyzer database. Patients with >=1 prescription for sac/val
      during 1 January-31 December 2016 (n = 1643) were identified and followed up for
      <=12 months from first prescription. Patients with >=1 heart failure (HF)
      diagnosis during the study period, >=1 additional HF diagnosis in the full
      history of the database, and >=1 prescription for an angiotensin-converting
      enzyme inhibitor or angiotensin receptor blocker and a beta-blocker during the
      study period, without a prescription for sac/val (n = 25,264), were included as a
      reference cohort. Changes in clinical parameters in the 12 months before and
      after sac/val initiation were investigated and compared with those from the
      PARADIGM-HF study. RESULTS: The characteristics of patients prescribed sac/val
      more closely resembled those of patients enrolled in PARADIGM-HF (e.g. younger
      age, higher proportion of men than women, lower systolic blood pressure) than
      patients in the reference cohort. Most patients were initiated on the lowest dose
      of sac/val irrespective of clinical setting. Significant decreases (p < 0.001) in
      NT-proBNP and glycated haemoglobin levels were observed following sac/val
      initiation. CONCLUSIONS: Patients prescribed sac/val had similar baseline
      demographics and clinical characteristics to those from PARADIGM-HF, and most
      patients were initiated on the lowest dose. Changes in clinical parameters before
      and after initiation mirrored findings from the PARADIGM-HF study.

PMID- 29446693
TI  - Hyperparathyroidism Mimicking Metastatic Bone Disease: A Case Report and Review
      of Literature.
AB  - Multiple osteolytic lesions are usually associated with metastatic involvement of
      the bone; however, metabolic bone diseases should also be included in the
      differential diagnosis. In this study, we describe a case of primary
      hyperparathyroidism (PHPT) with multiple osteolytic lesions that was diagnosed
      initially as having metastatic bone involvement. The laboratory results showed
      hypercalcemia and raised alkaline phosphatase along with fibrosis in the bone
      marrow biopsy with no increase in tumor markers and normal serum protein
      electrophoresis. The parathyroid hormone levels were high, which pointed toward a
      diagnosis of PHPT. Sestamibi scan revealed uptake at the level of the left
      inferior pole of the thyroid gland, which was suggestive of parathyroid adenoma.
      The possibility of hyperparathyroidism should be kept in mind when a patient
      presents with multiple osteolytic lesions and hypercalcemia.

PMID- 29446694
TI  - Experimental measurement of forces during percutaneous dilatational tracheostomy.
AB  - The measurement of mechanical effects associated with the dilatation phase of a
      percutaneous dilatational tracheostomy is of primary importance to identify the
      causes of major complications associated with this procedure, such as tracheal
      cartilage subluxation or fracture and bleeding. Such information can be very
      useful also for the design of better instruments and procedures. The aim of this
      study was to present a methodology to evaluate mechanical effects of the
      dilatation phase of a percutaneous dilatational tracheostomy on the tracheal
      rings and adjacent anatomical structures. Forces and moments were measured
      through a dilator instrumented with strain gauges. Two surgeons, with different
      levels of expertise, performed the percutaneous dilatational tracheostomy on a
      lifelike reproduction of an adult head, specifically designed for training
      professionals. The modified dilator was effective in measuring forces involved in
      the percutaneous dilatational tracheostomy without affecting the ability of the
      operator to perform the procedure. The main contribution to the insertion of the
      dilator was given by the axial force, defined as the force acting on the handle,
      compressing it (mean and peak force: 48.8 and 88.2 N for Surgeon 1, 31.3 and 82.8
      N for Surgeon 2, respectively). The proposed method was effective in measuring
      differences between procedures performed by surgeons with different amounts of
      experience in terms of duration, forces applied and repeatability. In addition,
      it may have applications for use as a feedback for incorrect positioning or
      excessively variable pressure during the training of surgeons for the execution
      of percutaneous dilatational tracheostomy.

PMID- 29446695
TI  - Weight-shift ability significantly correlates with walking velocity in post-acute
      stroke patients.
AB  - The ability to shift weight toward the paretic leg has been considered an
      essential ability to restore independent walking for post-acute stroke patients.
      However, few data are available regarding the relationship between the weight
      shift ability and gait performance. No clear mechanism has been provided as to
      why and how the weight-shift ability improves walking performance in stroke
      patients. We therefore investigated changes in the weight-shift ability and
      kinematic and kinetic parameters of walking gait in post-stroke patients during
      rehabilitation. Eight male inpatients undergoing rehabilitation for moderate
      hemiplegia participated in this study. Measurements were taken every 4 weeks from
      when the participants were able to walk at least 10 m until they were discharged
      from the hospital. Our results demonstrated a significant overall correlation
      between the weight-shift ability and walking velocity, indicating that the
      improvement in the weight-shift ability toward the paretic leg by lateral tilting
      of the thorax is fundamentally important to improve walking velocity. We also
      found that the upward impulse and vertical ground reaction force exerted by the
      paretic leg were significantly correlated with the walking velocity to cope with
      the downward impulse due to gravity and to allow sufficient time to swing the non
      paretic leg forward during walking. Therefore, improvement in the weight-shift
      ability is crucial for restoration of walking velocity. We believe that weight
      shift training for the paretic leg while instructing the patients to laterally
      tilt the thorax should be advocated as an effective protocol during
      rehabilitation of post-acute stroke inpatients.

PMID- 29446696
TI  - Expression profiles of stress-related genes in islets from donors with
      progressively impaired glucose metabolism.
AB  - It is currently unknown how the islet transcriptional pattern changes as glucose
      metabolism deteriorates and progresses to fulminant type 2 diabetes (T2D). In
      this study, we hypothesized that islets from donors with elevated HbA1c levels,
      but not yet diagnosed with T2D, would show signs of cell stress on a
      transcriptional level. Laser capture microdissection and qPCR arrays including
      330 genes related to mitochondria, oxidative stress, or the unfolded protein
      response were used to extract and analyze islets from organ donors with HbA1c
      <5.5% (37 mmol/mol), elevated HbA1c (6.0-6.5% (42-48 mmol/mol)), high HbA1c
      (>6.5% (48 mmol/mol)) or established T2D. Principal component analysis and
      hierarchical clustering based on the expression of all 330 genes displayed no
      obvious separation of the four different donor groups, indicating that the inter
      donor variations were larger than the differences between groups. However, 44
      genes were differentially expressed (P < 0.05, false discovery rate <30%) between
      islets from donors with HbA1c <5.5% (37 mmol/mol) compared with islets from T2D
      subjects. Twelve genes were differentially expressed compared to control islets
      in both donors with established T2D and donors with elevated HbA1c (6.0-6.5% (42
      48 mmol/mol)). Overexpressed genes were related mainly to the unfolded protein
      response, whereas underexpressed genes were related to mitochondria. Our data on
      transcriptional changes in human islets retrieved by LCM from high-quality
      biopsies, as pre-diabetes progresses to established T2D, increase our
      understanding on how islet stress contributes to the disease development.

PMID- 29446697
TI  - Psychedelics and the essential importance of context.
AB  - Psychedelic drugs are making waves as modern trials support their therapeutic
      potential and various media continue to pique public interest. In this opinion
      piece, we draw attention to a long-recognised component of the psychedelic
      treatment model, namely 'set' and 'setting' - subsumed here under the umbrella
      term 'context'. We highlight: (a) the pharmacological mechanisms of classic
      psychedelics (5-HT2A receptor agonism and associated plasticity) that we believe
      render their effects exceptionally sensitive to context, (b) a study design for
      testing assumptions regarding positive interactions between psychedelics and
      context, and (c) new findings from our group regarding contextual determinants of
      the quality of a psychedelic experience and how acute experience predicts
      subsequent long-term mental health outcomes. We hope that this article can: (a)
      inform on good practice in psychedelic research, (b) provide a roadmap for
      optimising treatment models, and (c) help tackle unhelpful stigma still
      surrounding these compounds, while developing an evidence base for long-held
      assumptions about the critical importance of context in relation to psychedelic
      use that can help minimise harms and maximise potential benefits.

PMID- 29446698
TI  - Radiological fibrosis score is strongly associated with worse survival in
      rheumatoid arthritis-related interstitial lung disease.
AB  - OBJECTIVES: High-resolution computed tomography (HRCT) parenchymal patterns have
      been used to predict prognosis in patients with interstitial lung disease (ILD).
      In idiopathic pulmonary fibrosis, the fibrosis score (i.e. the combined extent of
      reticulation and honeycombing) has been associated with worse survival. This
      study aimed to identify HRCT patterns and patient characteristics that can
      predict poor prognosis in rheumatoid arthritis-related ILD (RA-ILD). METHODS: We
      retrospectively analysed 65 patients with newly diagnosed RA-ILD from 2007 to
      2016 at Kurashiki Central hospital. Using univariate and bivariate Cox regression
      analysis, associations with mortality, were identified. RESULTS: During a median
      follow-up of 56.5 months, 16/65 (24.6%) patients died. Univariate analysis
      identified six significant poor prognostic factors: lower baseline % predicted
      forced vital capacity, total interstitial disease score, reticulation score,
      traction bronchiectasis score, fibrosis score, and definite UIP pattern. Fibrosis
      score remained to be an independently significant poor prognostic factor of
      survival on bivariate analysis. Patients with a fibrosis score >20% had higher
      mortality (HR, 9.019; 95% CI, 2.87-28.35; p < .05). CONCLUSION: This study showed
      that fibrosis score is strongly associated with worse survival in RA-ILD, and
      patients with fibrosis score >20% had a 9.019-fold increased risk of mortality.

PMID- 29446699
TI  - Investigating d-cycloserine as a potential pharmacological enhancer of an
      emotional bias learning procedure.
AB  - The partial N-methyl-D-aspartate receptor agonist d-cycloserine may enhance
      psychological therapies. However, its exact mechanism of action is still being
      investigated. Cognitive bias modification techniques allow isolation of cognitive
      processes and thus investigation of how they may be affected by d-cycloserine. We
      used a cognitive bias modification paradigm targeting appraisals of a stressful
      event, Cognitive Bias Modification-Appraisal, to investigate whether d
      cycloserine enhanced the modification of appraisal, and whether it caused greater
      reduction in indices of psychopathology. Participants received either 250 mg of d
      cycloserine ( n=19) or placebo ( n=19). As a stressor task, participants recalled
      a negative life event, followed by positive Cognitive Bias Modification-Appraisal
      training. Before and after Cognitive Bias Modification-Appraisal, appraisals and
      indices of psychopathology related to the stressor were assessed. Cognitive Bias
      Modification-Appraisal successfully modified appraisals, but d-cycloserine did
      not affect appraisals post-training. There were no post-training group
      differences in frequency of intrusions. Interestingly, d-cycloserine led to a
      greater reduction in distress and impact on state mood from recalling the event,
      and lower distress post-training was associated with fewer intrusions. Therefore,
      d-cycloserine may affect emotional reactivity to recalling a negative event when
      combined with induction of a positive appraisal style, but via a mechanism other
      than enhanced learning of the appraisal style.

PMID- 29446700
TI  - An interview-informed synthesized contingency analysis to inform the treatment of
      challenging behavior in a young child with autism.
AB  - PURPOSE: Experimental Functional analysis (EFA) is considered the "gold standard"
      of behavioural assessment and its use is predictive of treatment success.
      However, EFA has a number of limitations including its lengthy nature, the high
      level of expertise required, and the reinforcement of challenging behaviour. This
      study aimed to further validate a novel interview-informed synthesised
      contingency analysis (IISCA). METHODS: An open-ended interview and brief direct
      observation informed an IISCA for a young boy with autism who engaged in
      challenging behaviour. Resulting data supported the hypothesis that the target
      behaviour was multiply controlled by escape from demands and access to tangible
      items. An intervention comprised of most-to-least prompting, escape extinction,
      differential reinforcement and a high-probability instruction sequence was
      evaluated using a reversal design. RESULTS: This intervention reduced challenging
      behaviour to low levels and resulted in increased compliance. CONCLUSIONS:
      Findings support the status of the IISCA as a valid, practical, and effective
      process for designing function-based interventions.

PMID- 29446702
TI  - How Does Usage of Serotonin Noradrenaline Reuptake Inhibitors Affect Intraocular
      Pressure in Depression Patients?
AB  - PURPOSE: To evaluate anterior segment parameters and intraocular pressure (IOP)
      modifications in patients using serotonin noradrenaline reuptake inhibitors
      (SNRIs) due to major depressive disorder. METHODS: This cross-sectional study
      included 170 eyes of 85 subjects. All subjects were divided into three groups:
      group 1 included 44 healthy control subjects, group 2 included 22 patients
      receiving antidepressants for 1 week to 6 months, and group 3 included 19
      patients receiving antidepressants for >6 months. All subjects underwent a
      detailed ophthalmologic examination, including gonioscopy. Anterior segments of
      all subjects were evaluated with the Scheimpflug system and pupil diameter (PD),
      central corneal thickness, anterior chamber depth (ACD), anterior chamber volume,
      and anterior chamber angle (ACA) measurements were enrolled. RESULTS: The median
      IOP was significantly lower in patients using antidepressants [16.0 (11.0-21.0)
      mmHg] than the control group [17.5 (12.0-21.0) mmHg] (P = 0.041). The PD was
      significantly larger in patients using antidepressants [3.56 (2.29-5.60) mm] than
      the control group [2.95 (2.00-4.40) mm] (P = 0.000). In the study group, PD was
      also significantly larger in patients using SNRIs for >=6 months [3.67 (2.38
      5.08) mm] than <6 months [3.31 (2.29-5.60) mm] (P = 0.000). The median ACD was
      significantly lower in patients using antidepressants for >=6 months [3.21 (2.52
      4.06) mm] than the control group [3.44 (2.63-4.29) mm] (P = 0.000). ACAs were
      measured between 25 degrees  and 55 degrees  by Scheimpflug imaging. CONCLUSIONS:
      Treatment of SNRIs causes mydriasis and decrease in width of ACD. These changes
      may not increase IOP as long as the patient has an open angle. SNRIs lead to
      decrease in IOP particularly in long-term usage.

PMID- 29446701
TI  - Endoscopic Excision of Benign Facial Masses in Children: A Review of Outcomes.
AB  - PURPOSE: Benign masses of the eyebrow and forehead are common in pediatric
      patients and can result in facial asymmetry, discomfort, or super-infection.
      Excision is classically conducted via an incision directly over the mass, which
      can produce sub-optimal cosmesis. Recently, an endoscopic approach using
      pediatric brow-lift equipment has been adopted. We reviewed our center's
      experience with endoscopic removal of benign facial lesions and compared these
      cases with an equivalent series of open cases. MATERIALS AND METHODS: A
      retrospective chart review was conducted to identify pediatric cases of
      endoscopic and open removal of benign eyebrow or forehead lesions at our
      institution from 2009 to 2016. Clinical and cosmetic outcomes were reviewed.
      RESULTS: A total of 40 endoscopic and 25 open cases of excision of benign facial
      lesions in children were identified. For the patients who underwent endoscopic
      excision, the majority (85%) presented with a cyst located at the eyebrow.
      Histologic examination revealed 36 dermoid cysts (90%), 2 epidermal cysts, and 2
      pilomatrixomas. Of the 36 cases with post-operative follow-up, 32 patients (89%)
      had an uncomplicated recovery with good cosmesis. Two patients had an eyebrow
      droop that resolved without intervention. One patient had localized numbness
      overlying the site, but no motor deficits. One patient presented with a recurrent
      dermoid cyst that required open resection. For the patients who underwent open
      excision, the majority (52%) had dermoid cysts located at the eyebrow. Of the 22
      cases with follow-up, 20 of the patients had an uncomplicated recovery (90%).
      Comparing the rate of complications, there was no statistically significant
      difference between the two groups (P = 1.0). CONCLUSION: Endoscopic excision of
      benign forehead and eyebrow lesions in pediatric patients is feasible and yields
      excellent cosmetic results. When compared with open excision, complication rates
      are similar between both approaches and a facial scar can be avoided with an
      endoscopic approach.

PMID- 29446703
TI  - Use of the 5-mm Endoscopic Stapler for Ligation of Fistula in Laparoscopic
      Assisted Repair of Anorectal Malformation.
AB  - OBJECTIVE: Laparoscopic anorectoplasty (LARRP) for the treatment of select
      anorectal malformations has gained popularity due to enhanced visualization of
      the fistula and the ability to place the rectum within the sphincter complex
      while minimizing division of muscles and the perineal incision. However, given
      the technical challenges and reported complications of ligation, a number of
      techniques have been described, including using clips, suture ligation,
      endoloops, or division without closure. We aimed to evaluate fistula closure and
      division for high imperforate anus using a 5-mm stapler (JustRight Surgical,
      Boulder, CO). MATERIALS AND METHODS: A retrospective chart review was performed
      on patients who underwent LAARP for imperforate anus between March 2015 and
      December 2016. RESULTS: Four patients underwent LAARP with division of the
      fistula using the 5-mm stapler. The average age was 3.2 months and average weight
      was 4.5 kg. The location of the fistula was rectoprostatic in 3 cases and
      rectobladder neck in 1 case. There were no complications. CONCLUSION: Division of
      a fistula at or above the level of the prostate can safely and effectively be
      performed with the 5-mm stapler. The stapler allows for division flush with the
      urethra or bladder ergonomically and quickly.

PMID- 29446705
TI  - Prospective Assessment of Rhinovirus Symptoms and Species Recurrence in Children
      With and Without an Acute Wheezing Exacerbation.
AB  - To assess if the difference in species-specific immune response to RV-C
      correlates with a higher frequency of reinfection, shorter time to reinfection,
      or different symptom severity than infections with RV-A or RV-B. Forty-three
      patients were enrolled of which 34 were successfully tracked longitudinally over
      3 months, with nasal swabs and symptom questionnaires provided every 2 weeks to
      identify rhinovirus (RV) strains and the concurrent symptomatology. No difference
      was found in the time to reinfection with an RV species between RV-C and RV-A or
      RV-B (p = 0.866). There was a trend toward more rapid reinfection with the same
      species in RV-C than RV-A (55.1 days vs. 67.9 days), but this failed to reach
      statistical significance (p = 0.105). RV infections were generally associated
      with only minor symptoms, with rhinorrhea being the only significantly associated
      symptom (p = 0.01). RV-C was shown to have higher levels of lethargy and wheeze
      than other RV species. Time to reinfection with subsequent RV is not influenced
      by the species of the preceding RV.

PMID- 29446704
TI  - Effect of sodium molybdate supplementation on high concentrations of Cu in liver
      of yearling bulls.
AB  - AIM: To determine the impact of sodium molybdate treatment, given weekly, on
      concentrations of Cu in liver, activity of liver enzymes, and weight gain over 4
      weeks, in yearling bulls with elevated concentrations of Cu in liver. METHODS:
      The study was carried on two commercial grazing farms in the Otago region of New
      Zealand in yearling Friesian bulls (n=150 on Farm A and n=49 on Farm B) with mean
      concentration of Cu in liver >3,000 umol/kg fresh weight. On Day 0, all animals
      were weighed and half were systematically allocated to treatment with sodium
      molybdate (3 mg/kg liveweight on Farm A and 7 mg/kg liveweight on Farm B); the
      remainder received no treatment (Control). Sodium molybdate was given as a drench
      weekly for 4 weeks and all animals were weighed again on Day 28. Ten animals on
      each farm (five from each treatment group) were systematically selected for blood
      sampling and liver biopsies on Days 0 and 28. Samples were analysed for
      concentrations of Cu in plasma, vitamin B12 in serum, activities of gamma
      glutamyl transferase, aspartate aminotransferase and glutamate dehydrogenase in
      serum, and concentrations of Cu and vitamin B12 in liver. Separate multivariable
      linear models were used to compare the change in outcome variables between Days 0
      and 28 between bulls that had been drenched with sodium molybdate or not.
      RESULTS: On Farm A, mean concentrations of Cu in liver on Day 28, as a percentage
      of concentrations on Day 0, for the control group was 55 (95% CI=40-73)% and for
      the treatment group was 73 (95% CI=43-111)%. On Farm B, the equivalent mean for
      the control group was 75 (95% CI=42-131)% and for the treatment group was 85 (95%
      CI=38-134)%. The multivariable linear models indicated that the changes in
      concentrations of Cu in liver, activities of liver enzymes and weight gain
      between Days 0 and 28 did not differ between the bulls treated or not with sodium
      molybdate (p>0.18). CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with sodium
      molybdate in one bolus at weekly intervals for 4 weeks did not affect
      concentrations of Cu in liver, activity of liver enzymes or weight gain in
      animals with high concentrations of Cu liver on two farms.

PMID- 29446706
TI  - A 3D finite element model of prophylactic vertebroplasty in the metastatic spine:
      Vertebral stability and stress distribution on adjacent vertebrae.
AB  - Background and Objective Patients with metastatically compromised vertebra can
      experience pathologic fracture with relevant neurological complications.
      Vertebroplasty is a low cost procedure and it can potentially prevent neurologic
      impairment if performed at an early stage. The aim of this study is to evaluate
      the effects of prophylactic vertebroplasty on stability of the metastatic spine
      and analyze load distribution at adjacent vertebrae. Setting A 3D finite element
      model of two spinal motion segments (L3-L5) was developed. A central core of
      elements was selected in L4 vertebral body and material properties of a lytic
      metastasis and successively PMMA were assigned. The model was settled in order to
      simulate a non-osteoporotic spine and an osteoporotic spine. Outcome Measures
      Vertebral stability was assessed by the measurement of vertebral bulge (VB) and
      vertebral height (VH) on L4. Load transfer on adjacent vertebrae was evaluated by
      observing the distribution of the von Mises stress on L3 and L5 endplates.
      Results The metastasis increased VB by 424% and VH by 626%, while prophylactic
      vertebroplasty decreased VB and VH by 99% and 95%, respectively, when compared to
      the normal/non-metastatic model. Prophylactic vertebroplasty increased the
      average von Mises stress of L3 lower endplate by 1.33% in the non-osteoporotic
      spine, while it increased to 16% in the osteoporotic model. Conclusions
      Prophylactic vertebroplasty could represent an interesting option to improve
      vertebral strength of metastatically compromised spine without excessively
      increasing the stresses on adjacent vertebrae in non-osteoporotic spine.

PMID- 29446707
TI  - Arsenic, cadmium, and mercury-induced hypertension: mechanisms and
      epidemiological findings.
AB  - Arsenic (As), cadmium (Cd), and mercury (Hg) are toxic elements widely
      distributed in the environment. Exposure to these elements was attributed to
      produce several acute and chronic illnesses including hypertension. The aim of
      this review is to provide a summary of the most frequently proposed mechanisms
      underlying hypertension associated with As, Cd, and Hg exposure including:
      oxidative stress, impaired nitric oxide (NO) signaling, modified vascular
      response to neurotransmitters and disturbed vascular muscle Ca2+ signaling, renal
      damage, and interference with the renin-angiotensin system. Due to the complexity
      of the vascular system, a combination rather than a singular mechanism needs to
      be considered. In addition, epidemiological findings showing the relationship
      between various biomarkers of metal exposure and hypertension are described.
      Given the complex etiology of hypertension, further epidemiological studies
      evaluating the roles of confounding factors such as age, gender, and life style
      are still necessary.

PMID- 29446708
TI  - Does local dynamic stability of kayak paddling technique affect the sports
      performance? A pilot study.
AB  - During competition, kayak athletes must optimally adapt to environmental factors
      (e.g. wind, waves) to achieve peak performance. However, the ability to adapt to
      such perturbations has never been assessed in kayak paddling. Therefore, the aim
      of the current study was to evaluate the local dynamic stability in sports
      technique of youth sprint kayak athletes. In a cross-sectional study, 14 healthy
      male athletes were recruited from an elite youth sprint kayak squad. During an
      incremental kayak ergometer test, mean power, heart rates and local dynamic
      technique stability of hands, arms, trunk and paddle were registered and the
      association with the athletes 2000 m free-water times were estimated using mixed
      models. The 2000 m free-water performance significantly predicted the paddles (p
      = .037) local dynamic stability whereas no association was found for the trunk or
      the upper extremity kinematics. In conclusion, kayak athletes with high
      performance capability over 2000 m paddling depict high local dynamic technique
      stability. This emphasizes the importance of a stable technique for advanced
      kayak skills, especially regarding paddling movements.

PMID- 29446709
TI  - Use aerobic energy expenditure instead of oxygen uptake to quantify exercise
      intensity and predict endurance performance.

PMID- 29446710
TI  - Early versus late cardiac remodeling during right ventricular pressure load and
      impact of preventive versus rescue therapy with endothelin-1 receptor blockers.
AB  - Pulmonary artery banding (PAB) causes right ventricular (RV) dysfunction,
      biventricular fibrosis, and apoptosis, which are attenuated by endothelin-1
      receptor blockade (ERB). Little is known about the time course of remodeling and
      whether early versus late ERB confers improved outcome. PAB was performed in five
      groups of rabbits: Shams, 3-wk PAB (3W), 6-wk PAB (6W), 6-wk PAB + ERB
      administered from day 1 (6WERB1), and 6-wk PAB + ERB administered from day 21
      (6WERB21). Biventricular development of profibrotic molecular signaling,
      fibrosis, apoptosis, and conductance catheter and echocardiography function were
      studied. Thirty-three rabbits [ n = 6-7 per group; 3.00 (0.23) kg, mean (SD)]
      developed half to full systemic RV pressures. Biventricular profibrotic signaling
      and collagen deposition [RV collagen: Shams 3.8 (0.58) vs. 3W 8.69 (2.52) vs. 6W
      8.83 (4.02)%, P < 0.005] and apoptosis [RV: Shams 8.32 (3.2) vs. 3W 55.95 (47.55)
      vs. 6W 38.85 (17.26) apoptotic cells per microfield, P < 0.0005] increased with
      PAB. Early and late ERB attenuated fibrosis [RV: 6WERB1 5.55 (1.18), 6WERB21 5.63
      (0.72)%] and apoptosis [RV: 6WERB1 11.1 (5.25), 6WERB21 20.24 (7.16) apoptotic
      cells per microfield, P < 0.0001 vs. 6W]. RV dimensions progressively increased
      at 3W and 6W and decreased with early ERB [end-diastolic dimensions: Shams 0.4
      (0.13) vs. 3W 0.55 (0.78) vs. 6W 0.78 (0.25) vs. 6WERB1 0.71 (0.26) vs. 6WERB21
      0.49 (0.23) cm, P < 0.05]. Despite increased RV contractility with PAB [RV end
      systolic pressure-volume relationship: Shams 3.76 (1.76) vs. 3W 12.21 (3.44) vs.
      6W 19.4 (6.88) mmHg/ml], biventricular function and cardiac output [Shams 196.1
      (39.73) vs. 3W 149.9 (34.82) vs. 6W 151 (31.69) ml/min] worsened in PAB groups
      and improved with early and late ERB [6WERB1 202.8 (26.8), 6WERB21 194.8 (36.93)
      ml/min, P < 0.05 vs. PAB]. In conclusion, RV pressure overload induces early
      biventricular fibrosis, apoptosis, remodeling, and dysfunction that worsens with
      persistent RV hypertension. This remodeling is attenuated by early and late ERB.
      NEW & NOTEWORTHY Our results in a rabbit model of progressive right ventricular
      (RV) pressure loading indicate that biventricular fibrosis, apoptosis, and
      dysfunction are already present when RV hypertension is reached at 3 wk of
      progressive pulmonary artery banding. These findings worsen with persistent RV
      hypertension to 6 wk and are attenuated with both early and late endothelin-1
      receptor blockade, with some advantages to early therapy. These findings
      highlight the role of endothelin-1 in driving biventricular remodeling secondary
      to RV hypertension and suggest that early therapy with an endothelin-1 receptor
      blocker may be beneficial in attenuating biventricular remodeling but that late
      therapy is also effective.

PMID- 29446711
TI  - Neurophysiological adaptations in the untrained side in conjunction with cross
      education of muscle strength: a systematic review and meta-analysis.
AB  - We reviewed the evidence from randomized controlled trials (RCTs) focusing on the
      neurophysiological adaptations in the untrained side associated with cross
      education of strength (CE) and pooled data into definite effect estimates for
      neurophysiological variables assessed in chronic CE studies. Furthermore, scoping
      directions for future research were provided to enhance the homogeneity and
      comparability of studies investigating the neural responses to CE. The magnitude
      of CE was 21.1 +/- 18.2% (mean +/- SD; P < 0.0001) in 22 RCTs ( n = 467 subjects)
      that measured at least 1 neurophysiological variable in the untrained side,
      including the following: electromyography (EMG; 14 studies); motor evoked
      potential (MEP; 8 studies); short-interval intracortical inhibition (SICI),
      recruitment curve, and M wave (6 studies); cortical silent period (cSP; 5
      studies); interhemispheric inhibition, intracortical facilitation (ICF), and H
      reflex (2 studies); and V wave, short-interval ICF, short-latency afferent
      inhibition, and long-latency afferent inhibition (1 study). Only EMG, MEP, ICF,
      cSP, and SICI could be included in the meta-analysis (18 studies, n = 387). EMG (
      P = 0.26, n = 235) and MEP amplitude ( P = 0.11, n = 145) did not change in the
      untrained limb after CE. cSP duration ( P = 0.02, n = 114) and SICI ( P = 0.001,
      n = 95) decreased in the untrained hemisphere according to body region and type
      and intensity of training. The magnitude of CE did not correlate with changes in
      these transcranial magnetic stimulation (TMS) measures. The design of this meta
      analytical study and the lack of correlations prevented the ability to link
      mechanistically the observed neurophysiological changes to CE. Notwithstanding
      the limited amount of data available for pooling, the use of TMS to assess the
      ipsilateral neurophysiological responses to unilateral training still confirms
      the central neural origin hypothesis of chronic CE induced by strength training.
      However, how these neural adaptations contribute to CE remains unclear.

PMID- 29446712
TI  - Measures of sympathetic and parasympathetic autonomic outflow from heartbeat
      dynamics.
AB  - Reliable and effective noninvasive measures of sympathetic and parasympathetic
      peripheral outflow are of crucial importance in cardiovascular physiology.
      Although many techniques have been proposed to take up this long-lasting
      challenge, none has proposed a satisfying discrimination of the dynamics of the
      two separate branches. Spectral analysis of heart rate variability is the most
      currently used technique for such assessment. Despite its widespread use, it has
      been demonstrated that the subdivision in the low-frequency (LF) and high
      frequency (HF) bands does not fully reflect separate influences of the
      sympathetic and parasympathetic branches, respectively, mainly due to their
      simultaneous action in the LF. Two novel heartbeat-derived autonomic measures,
      the sympathetic activity index (SAI) and parasympathetic activity index (PAI),
      are proposed to separately assess the time-varying autonomic nervous system
      synergic functions. Their efficacy is validated in landmark autonomic maneuvers
      generally employed in clinical settings. The novel measures move beyond the
      classical frequency domain paradigm through identification of a set of
      coefficients associated with a proper combination of Laguerre base functions. The
      resulting measures were compared with the traditional LF and HF power. A total of
      236 ECG recordings were analyzed for validation, including autonomic outflow
      changes elicited by procedures of different nature and temporal variation, such
      as postural changes, lower body negative pressure, and handgrip tests. The
      proposed SAI-PAI measures consistently outperform traditional frequency-domain
      indexes in tracking expected instantaneous autonomic variations, both vagal and
      sympathetic, and may aid clinical decision making, showing reduced intersubject
      variability and physiologically plausible dynamics. NEW & NOTEWORTHY While it is
      possible to obtain reliable estimates of parasympathetic activity from the ECG, a
      satisfying method to disentangle the sympathetic component from HRV has not been
      proposed yet. To overcome this long-lasting limitation, we propose two novel HRV
      based indexes, the sympathetic and parasympathetic activity indexes.

PMID- 29446713
TI  - Mitigation of airways responsiveness by deep inflation of the lung.
AB  - Stretching activated strips of airway smooth muscle (ASM) significantly affects
      both active force and stiffness due to a temporary reduction of the proportion of
      cycling myosin cross bridges that are bound to their actin binding sites. For the
      same reason, stretch applied to ASM in situ by a deep inflation (DI) of the lungs
      is one of the most potent means of reversing bronchoconstriction. When the DI is
      sufficiently large, however, and is applied while bronchoconstriction is in the
      process of developing, the subsequent depression in airway resistance is more
      persistent than can be attributed simply to temporary detachment of ASM cross
      bridges. In the present study, we use a computational model to demonstrate that
      this DI-induced ablation of airway responsiveness can be explained by a dose
      dependent reduction in the number of cross bridges available to bind to actin
      when the ASM in the airway wall is stretched above a critical threshold strain
      and that this disruption of the contractile apparatus recovers over an order of
      magnitude longer time scale than that of the simple reattachment of unbound cross
      bridges. NEW & NOTEWORTHY The mechanisms by which deep inflation of the lung
      reverse bronchoconstriction and affect subsequent airway responsiveness have
      important potential implications for asthma, yet remain controversial. This study
      uses computational modeling to posit a mechanism by which sufficiently vigorous
      inflations applied during active bronchoconstriction not only transiently reverse
      bronchoconstriction, but also reduce subsequent airways responsiveness for a
      period of time. Fitting the model to published data in mice supports this notion.

PMID- 29446714
TI  - Blunted shear-mediated dilation of the internal but not common carotid artery in
      response to lower body negative pressure.
AB  - Shear-mediated dilation in peripheral conduit arteries is blunted with
      sympathetic nervous system (SNS) activation; however, the effect of SNS
      activation on shear-mediated dilation in carotid arteries is unknown. We
      hypothesized that SNS activation reduces shear-mediated dilation in common and
      internal carotid arteries (CCA and ICA, respectively), and this attenuation is
      greater in the ICA compared with the CCA. Shear-mediated dilation in the CCA and
      ICA were measured in nine healthy men (24 +/- 1 yr) with and without SNS
      activation. Shear-mediated dilation was induced by 3 min of hypercapnia (end
      tidal partial pressure of carbon dioxide +10 mmHg from individual baseline); SNS
      activity was increased with lower body negative pressure (LBNP; -20 mmHg). CCA
      and ICA measurements were made using Doppler ultrasound during hypercapnia with
      (LBNP) or without (Control) SNS activation. LBNP trials began with 5 min of LBNP
      with subjects breathing hypercapnic gas during the final 3 min. Shear-mediated
      dilation was calculated as the percent rise in peak diameter from baseline
      diameter. Sympathetic activation attenuated shear-mediated dilation in the ICA
      (Control vs. LBNP, 5.5 +/- 0.7 vs. 1.8 +/- 0.4%, P < 0.01), but not in the CCA
      (5.1 +/- 1.2 vs. 4.2 +/- 1.0%, P = 0.31). Moreover, absolute reduction in shear
      mediated dilation via SNS activation was greater in the ICA than the CCA (-3.6 +/
      0.7 vs. -0.9 +/- 0.8%, P = 0.02). Our data indicate that shear-mediated dilation
      is attenuated during LBNP to a greater extent in the ICA compared with the CCA.
      These results potentially provide insight into the role of SNS activation on
      cerebral perfusion, as the ICA is a key supplier of blood to the brain. NEW &
      NOTEWORTHY We explored the effect of acute sympathetic nervous system (SNS)
      activation on shear-mediated dilation in the common and internal carotid arteries
      (CCA and ICA, respectively) in young healthy men. Our data demonstrate that
      hypercapnia-induced vasodilation of the ICA is attenuated during lower body
      negative pressure to a greater extent than the CCA. These data may provide novel
      information related to the role of SNS activation on cerebral perfusion in
      humans.

PMID- 29446715
TI  - Update in Women's Heart Disease: Prevention and Screening.
AB  - The goal in selecting these recent articles was to help identify literature that
      may change the clinical practice of women's health for internists. Articles were
      identified by reviewing the high-impact medical and women's health journals,
      national guidelines, ACP JournalWise, and NEJM Journal Watch. Cardiovascular (CV)
      disease remains the leading cause of death in women. The emphasis of this review
      is on identifying opportunities for CV risk reduction to prevent disease and on
      early identification of women with preexisting atherosclerotic disease to allow
      for early initiation of medical treatment.

PMID- 29446716
TI  - Overactive Bladder and Lifestyle Factors.

PMID- 29446717
TI  - Activators of Sirtuin-1 and their Involvement in Cardioprotection.
AB  - SIRT1 is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase,
      which removes acetyl groups from many target proteins, such as histone proteins,
      transcription factors and cofactors. SIRT1-catalyzed deacetylation of these
      factors modulates the activity of downstream proteins, thus influencing many
      biological processes. SIRT1 is involved in the regulation of metabolism,
      inflammation, and tumor growth. The activity of this enzyme is related to the
      beneficial health effects of calorie restriction, such as lifespan extension and,
      in particular, the activation of SIRT1 has a positive impact on the
      cardiovascular system. Therefore, SIRT1 is considered as an attractive drug
      target and modulation of SIRT1 may represents a new therapeutic strategy against
      cardiovascular diseases, as small molecules able to activate SIRT1 can be
      considered as cardioprotective agents. In this review, we summarize both natural
      or synthetic compounds developed as SIRT1 activators, with a focus on their
      promising therapeutic applications in cardiovascular pathologies.

PMID- 29446718
TI  - Current Trends and Future Directions of Fluoroquinolones.
AB  - Fluoroquinolones represent an interesting synthetic class of antimicrobial agents
      with broad spectrum and potent activity. Since the discovery of nalidixic acid,
      the prototype of quinolones, several structural modifications to the quinolone
      nucleus have been carried out for improvement of potency, spectrum of activity,
      and to understand their structure activity relationship (SAR). The C-7
      substituent was reported to have a major impact on the activity. Accordingly,
      Substitution at C-7 or its N-4-piperazinyl moiety was found to affect potency,
      bioavailability, and physicochemical properties. Also, it can increase the
      affinity towards mammalian topoisomerases that may shift quinolones from
      antibacterial to anticancer candidates. Moreover, the presence of DNA
      topoisomerases in both eukaryotic and prokaryotic cells makes them excellent
      targets for chemotherapeutic intervention in antibacterial and anticancer
      therapies. Based on this concept, several fluoroquionolones derivatives have been
      synthesized and biologically evaluated as antibacterial, antituberculosis,
      antiproliferative, antiviral and antifungal agents. This review is an attempt to
      focus on the therapeutic prospects of fluoroquinolones with an updated account on
      their atypical applications such as antitubercular and anticancer activities.

PMID- 29446719
TI  - DNA Double Strand Breaks Repair Inhibitors: Relevance as Potential New Anticancer
      Therapeutics.
AB  - DNA Double-strand breaks are considered one of the most lethal form of DNA
      damage. Many effective anticancer therapeutic approaches used chemical and
      physical methods to generate DNA double-strand breaks in the cancer cells. They
      include: IR and drugs which mimetic its action, topoisomerase poisons, some
      alkylating agents or drugs which affected DNA replication process. On the other
      hand, cancer cells are mostly characterized by highly effective systems of DNA
      damage repair. There are two main DNA repair pathways used to fix double-strand
      breaks: NHEJ and HRR. Their activity leads to a decreased effect of chemotherapy.
      Targeting directly or indirectly the DNA double-strand breaks response by
      inhibitors seems to be an exciting option for anticancer therapy and is a part of
      novel trends that arise after the clinical success of PARP inhibitors. These
      trends will provide great opportunities for the development of DNA repair
      inhibitors as new potential anticancer drugs. The main objective of this article
      is to address these new promising advances.

PMID- 29446720
TI  - Electrochemistry of Alzheimer Disease Amyloid Beta Peptides.
AB  - Alzheimer's disease (AD) is a widespread form of dementia that is estimated to
      affect 44.4 million people worldwide. AD pathology is closely related to the
      accumulation of amyloid beta (Abeta) peptides in fibrils and plagues, the small
      oligomeric intermediate species formed during the Abeta peptides aggregation
      presenting the highest neurotoxicity. This review discusses the recent advances
      on the Abeta peptides electrochemical characterization. The Abeta peptides
      oxidation at a glassy carbon electrode occurs in one or two steps, depending on
      the amino acid sequence, length and content. The first electron transfer reaction
      corresponds to the tyrosine Tyr10 amino acid residue oxidation, and the second to
      all three histidine (His6, His13 and His14) and one methionine (Met35) amino acid
      residues. The Abeta peptides aggregation and amyloid fibril formation are
      electrochemically detected via the electroactive amino acids oxidation peak
      currents decrease that occurs in a time dependent manner. The Abeta peptides
      redox behaviour is correlated with changes in the adsorption morphology from
      initially random coiled structures, corresponding to the Abeta peptide monomers
      in random coil or in alpha-helix conformations, to aggregates, protofibrils and
      two types of fibrils, corresponding to the Abeta peptides in a beta-sheet
      configuration, observed by atomic force microscopy. Electrochemical studies of
      Abeta peptides aggregation, mediated by the interaction with metal ions,
      particularly zinc, copper and iron, and different methodologies concerning the
      detection of Abeta peptide biomarkers of AD in biological fluids, using
      electrochemical biosensors, are also discussed.

PMID- 29446721
TI  - Fluorescent Imaging of Amyloid-beta Deposits in Brain: An Overview of Probe
      Development and a Highlight of the Applications for In Vivo Imaging.
AB  - The beta-amyloid (Abeta) plaques presented within the brain parenchyma have been
      widely proved to be one of the hallmarks of Alzheimer's disease (AD). According
      to the amyloid cascade hypothesis, the accumulation of Abeta plaques in the brain
      is intrinsic and fundamental for disease onset, and much research about the early
      diagnosis of AD is based on this. A recent development in Abeta detection has
      focused on the mapping of the molecule events in the brain using an exquisite,
      noninvasive, and inexpensive optical imaging technique, which has stimulated the
      rapid development of Abeta-specific fluorescent probes. Among them, nearinfrared
      (NIR) fluorophores have gained adequate attention due to the weak light
      attenuation in tissues and avoidance from auto-fluorescence of biological matter.
      In this review, we showcase the current developments of fluorescent probes that
      are subject to in vitro or in vivo detection of Abeta plaques in the brain, and
      give an emphasis on the probes used for in vivo twophoton microscopy and NIR
      imaging by highlighting their biological and photochemical properties.

PMID- 29446722
TI  - Herbal compounds with special reference to gastrodin as potential therapeutic
      agents for microglia mediated neuroinflammation.
AB  - BACKGROUND: Activated microglia play a pivotal role neurodegenerative diseases by
      producing a variety of proinflammatory mediators including tumor necrosis factor
      alpha (TNF-alpha), interleukin-1bea (IL-1beta) and nitric oxide (NO) that are
      toxic to neurons and oligodendrocytes. METHODS: In view of the above, suppression
      of microglia mediated neuroinflammation is deemed a therapeutic strategy for
      neurodegenerative diseases. Several potential Chinese herbal extracts have been
      reported to exert neuroprotective effects against neurodegenerative diseases
      targeting specifically at the activated microglia. In this connection, the
      phenolic glucoside gastrodin, a main constituent of the Chinese herbal medicine
      Gastrodia rhizoma, produced widely in the local community exhibits potential
      neuroprotective effects through suppression of neurotoxic proinflammatory
      mediators. RESULTS: Here, we first review the roles of activated microglia in
      different brain diseases. The effects of gastrodin on activated microglia are
      then considered. We have identified gastrodin as a putative therapeutic agent as
      it has been found to suppress microglial activation thus ameliorating
      neuroinflammation. More importantly, gastrodin downregulates the expression of
      renin angiotensin system (RAS) and production of proinflammatory mediators.
      Remarkably, gastrodin promotes Sirtuin 3 (Sirt3) up-regulation and nicotinamide
      adenine dinucleotide phosphate oxidase-2 (NOX-2) down-regulation after ischemic
      hypoxia in activated microglia mediated by AT1 or AT2 receptors which are
      angiotensin II receptors subtypes, indicating a possible molecular link between
      RAS and Sirt3 survival genes. CONCLUSION: This review summarizes the beneficial
      effects of gastrodin acting on activated microglia along with other herbal
      compounds. Its efficacy in neuroprotection is consistent with some common herbal
      products in China.

PMID- 29446723
TI  - Immunomodulatory Effects of Flavonoids in the Prophylaxis and Treatment of
      Inflammatory Bowel Diseases: A Comprehensive Review.
AB  - Inflammatory Bowel Diseases (IBD) comprised of two disorders of idiopathic
      chronic intestinal inflammation that affect about three million people worldwide:
      Crohn's disease and ulcerative colitis. Nowadays, the first-line of treatment for
      patients with mild to moderate symptoms of IBD is comprised of corticosteroids,
      immunosuppressants, antibiotics, and biological agents. Unfortunately, none of
      these drugs are curative, and their long-term use may cause severe side effects
      and complications. Almost 40% of IBD patients use alternative therapies to
      complement the conventional one, and flavonoids are gaining attention for this
      purpose. The biological properties of flavonoids are well documented and their
      antioxidant and anti-inflammatory activities have been arousing attention in the
      scientific community. Flavonoids are the most widely distributed polyphenols in
      plants and fruits, making part of the human diet. Taking into account that all
      ingested flavonoids are expected to exert biological actions at the
      gastrointestinal level, research on the modulatory effect of these compounds in
      IBD is of paramount importance. This review intends to summarize, in an
      integrated and comprehensive form, the effect of flavonoids, both in vitro and in
      vivo, in the different phases of the characteristic IBD inflammatory network.

PMID- 29446724
TI  - Inhibitors of ER aminopeptidase 1 and 2: from design to clinical application.
AB  - Endoplasmic Reticulum aminopeptidase 1 and 2 are two homologous enzymes that help
      generate peptide ligands for presentation by Major Histocompatibility Class I
      molecules. Their enzymatic activity influences the antigenic peptide repertoire
      and indirectly controls adaptive immune responses. Accumulating evidence suggests
      that these two enzymes are tractable targets for the regulation of immune
      responses with possible applications ranging from cancer immunotherapy to
      treating inflammatory autoimmune disease. Here, we review the state-of-the-art in
      the development of inhibitors of ERAP1 and ERAP2 as well as their potential and
      limitations for clinical applications.

PMID- 29446725
TI  - Mapping of Protein-Protein Interactions: Web-Based Resources for Revealing
      Interactomes.
AB  - BACKGROUND: The significant number of protein-protein interactions (PPIs)
      discovered by harnessing concomitant advances in the fields of sequencing,
      crystallography, spectrometry and two-hybrid screening suggests astonishing
      prospects for remodelling drug discovery. The PPI space which includes up to 650
      000 entities is a remarkable reservoir of potential therapeutic targets for every
      human disease. In order to allow modern drug discovery programs to leverage this
      we should be able to discern complete PPI maps associated with a specific
      disorder and corresponding normal physiology. OBJECTIVE: Here, we will review
      community available computational programs for predicting PPIs and web-based
      resources for storing experimentally annotated interactions. METHODS: We compared
      the capacities of prediction tools: iLoops, Struck2Net, HOMCOS, COTH, PrePPI,
      InterPreTS and PRISM to predict recently discovered protein interactions.
      RESULTS: We described sequence-based and structure-based PPI prediction tools and
      addressed their peculiarities. Additionally, since the usefulness of prediction
      algorithms critically depends on the quality and quantity of the experimental
      data they are built on, we extensively discussed community resources for protein
      interactions. We focused on the active and recently updated primary and secondary
      PPI databases, repositories specialized to the subject or species, as well as
      databases that include both experimental and predicted PPIs. CONCLUSION: PPI
      complexes are the basis of important physiological processes and therefore,
      possible targets for cell-penetrating ligands. Reliable computational PPI
      predictions can speed up new target discoveries through prioritization of
      therapeutically relevant protein-protein complexes for experimental studies.

PMID- 29446726
TI  - Metal-organic framework (MOF)-based nanomaterials for biomedical applications.
AB  - Metal-organic frameworks (MOFs) are compounds consisting of metal ions or
      clusters coordinated to organic ligands to form one-, two-, or three-dimensional
      structures. They are a subclass of coordination polymers (CPs), with the special
      feature that they are often porous. The organic ligands are sometimes referred to
      as second building structs. The new porous materials have paid great attention
      because of the variety of advantages such as tunable components, structural
      diversity, high loading performance and favorable biodegradability. In this
      review, we highlighted the recent progress on the drug delivery application of
      MOFs, especially emphasizing the application of pH-responsive delivery as well as
      magnetic-guided drug delivery systems (DDSs). Subsequently, the applications of
      MOFs in magnetic resonance imaging (MRI), optical imaging (OI), X-ray computed
      tomography (CT) imaging and multimodality imaging will be discussed. Finally, we
      will provide an overview for the photodynamic therapy and the toxicity feature of
      MOFs.

PMID- 29446727
TI  - Natural Terpenoids Against Female Breast Cancer: A 5-year Recent Research.
AB  - BACKGROUND: The approval of Taxol(r) in 1993 marked the great entrance of
      terpenoids in the anti-cancer area and this drug is still highly important in the
      treatment of refractory ovarian, breast and other cancers. Over decades, other
      prominent natural terpenoids have become indispensable for the modern
      pharmacotherapy of breast cancer. However, given the rapid evolution of drug
      resistance, effective treatments for advanced breast cancers requiring cytotoxic
      chemotherapy represent a major unmet clinical need. Therefore, innovative agents
      effective in long-term chemotherapy are urgently needed. OBJECTIVE: This review
      examines recent advances/research about natural terpenoids, and their mechanisms
      against female breast cancer over the period covering January 1st, 2012 to
      December 31st, 2016. RESULTS: Carcinogenesis constitutes a multistep process
      wherein each stage is characterized by distinct phenotypic changes. Numerous
      chemicals recorded in this review have been shown to significantly inhibit
      proliferation, migration, apoptosis resistance, tumor angiogenesis or metastasis
      in different breast cancer cells/tumours in vitro and in vivo. Targeting
      simultaneously several or all these aspects/steps of cancer progression could be
      an advantage. In line with this, phytochemicals such as thymoquinone (8),
      costunolide (46), tanshinone IIA (132), triptolide (136), cucurbitacin B (179),
      celastrol (226) and lycopene (238) had caught our attention. CONCLUSION: These
      compounds appear to be promising to overcome breast cancer treatment failure.
      However, despite the interesting activities, additional preclinical
      investigations are needed in further breast cancer cell/tumor models in vitro and
      in vivo.

PMID- 29446728
TI  - Recent advances in the use of metallic nanoparticles with antitumoral action.
AB  - The term cancer represents a set of more than 100 diseases that are caused due to
      an uncontrolled growth of cells; and their subsequent spread to the other tissues
      and organs of the body by a phenomenon, called 'metastasis'. According to the
      estimates provided by the World Health Organization (WHO), cancer is expected to
      account for about 10 million deaths per year by 2020, and 21 million cancer
      cases, which may lead to 13 million deaths by 2030, making cancer as the cause of
      highest mortality in contrast to other diseases. The search for potential
      therapeutics against cancer, which can reduce the side-effects that occur due to
      the difficulty of recognition between cancerous and normal cells, has ever been
      increased. In this view, nanotechnology, especially metallic nanoparticles
      (MNPs), comes to aid in the development of novel therapeutic agents, which may be
      synthesized or modified with the most diverse functional chemical groups; this
      property makes the metallic nanoparticles suitable for conjugation with already
      known drugs or prospective drug candidates. The biocompatibility, relatively
      simple synthesis, size flexibility and easy chemical modification of its surface,
      all make the metallic nanoparticles highly advantageous for opportune diagnosis
      and therapy of cancer. The present article analyzes and reports the anti-tumor
      activities of 78 papers of various metallic nanoparticles, particularly the ones
      containing copper, gold, iron, silver, and titanium in their composition.

PMID- 29446729
TI  - Recent Progress in the Development of Fluorometric Chemosensors to Detect
      Enzymatic Activity.
AB  - Enzymes are a class of macromolecules that function as highly efficient and
      specific biological catalysts requiring only mild reaction conditions. Enzymes
      are essential to maintaining life activities, including promoting metabolism and
      homeostasis, and participating in a variety of physiological functions.
      Accordingly, enzymatic levels and activity are closely related to the health of
      the organism, where enzymatic dysfunctions often lead to corresponding diseases
      in the host. Because of this, diagnosis of certain diseases is based on the
      levels and activity of certain enzymes. Therefore, rapid real-time and accurate
      detection of enzymes in situ is important for diagnosis, monitoring, clinical
      treatment, and pathological studies of disease. Fluorescent probes have unique
      advantages in terms of detecting enzymes, including being simple to use in highly
      sensitive and selective real-time rapid in-situ non-invasive and highly spatial
      resolution visual imaging. However, fluorescent probes are most commonly used to
      detect oxidoreductases, transferases, and hydrolases due to the processes and
      types of enzyme reactions. This paper summarizes the application of fluorescent
      probes to detect these three types of enzymes over the past five years. In
      addition, we introduce the mechanisms underlying detection of these enzymes by
      their corresponding probes.

PMID- 29446730
TI  - Salvaging the ischemic heart: Gi-coupled receptors in mast cells activate a
      PKCepsilon/ALDH2 pathway providing anti-RAS cardioprotection.
AB  - BACKGROUND: Excessive norepinephrine (NE) release in the ischemic heart elicits
      severe and often lethal arrhythmias. Resident cardiac mast cells synthesize and
      store active renin, which is released upon degranulation, causing the activation
      of a local cardiac renin-angiotensin system (RAS) responsible for NE release and
      consequent arrhythmias. Toxic aldehydes, known to be formed by lipid peroxidation
      in ischemia/reperfusion (I/R), have been shown to degranulate mast cells and
      activate a local RAS. OBJECTIVE: To provide an up-to-date description of the
      roles of ischemic preconditioning (IPC) and Gi-coupled receptors in anti-RAS
      cardioprotection. METHODS: Ex-vivo I/R models in cavian and murine hearts, and
      human and murine mast cell lines in vitro. RESULTS: IPC not only drastically
      reduces the injury subsequent to a prolonged ischemic event, but also decreases
      mast cell renin release, thus affording anti-RAS cardioprotection. Similarly,
      activation of Gi-coupled receptors, such as histamine-H4, adenosine-A3 and
      sphingosine-1-phosphate-S1P1 receptors, all expressed at the mast cell surface,
      mimic the cardioprotective anti-RAS effects of IPC. The mechanism of this action
      depends on the sequential activation of a specific isoform of protein kinase C,
      PKCepsilon, and mitochondrial aldehyde dehydrogenase-type 2 (ALDH2). Increased
      ALDH2 enzymatic activity exerts a pivotal role in the sequential inhibition of
      aldehyde-induced mast-cell renin release, prevention of RAS activation, reduction
      of NE release and alleviation of reperfusion arrhythmias. CONCLUSION: These
      recently discovered protective pathways indicate that activation of mast-cell Gi
      coupled receptors and subsequent ALDH2 phosphorylation/activation represent a
      novel therapeutic target for the alleviation of RAS-induced cardiac dysfunctions,
      including ischemic heart disease and congestive heart failure.

PMID- 29446732
TI  - Biomedical Potentialities of Taraxacum officinale-based Nanoparticles
      Biosynthesized Using Methanolic Leaf Extract.
AB  - BACKGROUND: In the present study, the potential of methanolic leaf extract of
      Taraxacum officinale plant as a function of bio-inspired green synthesis for the
      fabrication of silver nanoparticles (AgNPs) has been explored. METHODS: The bio
      reduction of aqueous silver nitrate (AgNO3) solution was confirmed by visually
      detecting the color change from pale yellow to blackish-brown. Maximum absorbance
      was observed at 420 nm due to the presence of characteristic surface Plasmon
      resonance of nano silver by UV-visible spectroscopy. The role of various
      functional groups in the bio-reduction of silver and chemical transformation was
      verified by Fourier transform infrared spectroscopy (FTIR). Scanning electron
      microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) predict the shape
      (rocky, flack type, ellipsoidal, etc.), size (68 nm) and elemental composition
      (Ag as a major constituent) of the biosynthesized AgNPs, respectively. RESULTS:
      Transmission electron microscopy (TEM) analysis further corroborated the
      morphology of the AgNPs. Color mapping and atomic force microscopy (AFM)
      confirmed the nano-sized topography. The dynamic light scattering (DLS) showed
      the charge, stability, and size of the AgNPs. The generated AgNPs presented
      potential antibacterial activities against Gram-positive and Gram-negative
      bacterial strains including Staphylococcus aureus, Escherichia coli, and
      Haemophilus influenzae. The biosynthesized AgNPs also showed antiproliferative
      activity against MCF-7 breast cancer cell line in a dosedependent manner.
      CONCLUSION: In conclusion, results clearly indicate that biosynthesized AgNPs
      could be used as effective nano drug for treating infectious diseases caused by
      multidrug resistant bacterial strains in the near future.

PMID- 29446733
TI  - Current Understanding of Inflammatory Responses in Acute Kidney Injury.
AB  - Acute kidney injury has been a tough complex with increased mortality and
      morbidity. Inflammatory responses, including innate and adaptive immune
      responses, involve in the initiation and development of acute kidney injury,
      especially under the ischemic circumstances. Tubular cells and distinct immune
      cell subgroups play a critical role in the pathogenesis of inflammation. Current
      gene therapies show their benefits in renal repair. Here, we reviewed the renal
      inflammatory infiltration, inflammatory mediators, oxidative stress and potential
      signaling pathways, which give rise to the kidney diseases, in the mechanism of
      acute kidney injury. Recent studies showed diverse insights in understanding the
      pathophysiological process of inflammation related renal injury and provided
      novel clinical targets for ameliorating acute kidney injury by balancing the
      facilitation of repairing and prevention of impairing. Interestingly, antisense
      oligonucleotides of target sequence, local electransfering on solid organ and
      adenovirus-mediated certain gene overexpression have been promising strategies in
      alleviating acute kidney injury.

PMID- 29446735
TI  - Epigenetic Regulation of Regulatory T Cells in Kidney Disease and
      Transplantation.
AB  - Regulatory T (Treg) cells are a kind of immunosuppression cells, which have been
      used to treat autoimmune diseases and induce allograft tolerance in clinical
      trials. While Treg cells based therapy is a promising treatment for kidney
      diseases and an emerging concept for tolerance induction in renal
      transplantation, a better understanding of the functions and biology of Treg
      cells is needed to be able to optimally exploit them. Epigenetics regulation,
      which refers to potentially heritable alterations in gene expression without
      underlying changes of the nucleotide sequence, plays an important role in Treg
      cells induction and maintenance. The expression of Foxp3, the key factor of Treg
      cells, is regulated by DNA methylation, histone modification and post
      transcriptionally modification. Herein, we review the current understanding of
      Treg cells in kidney diseases and transplantation, and discuss the epigenetic
      regulation of Treg cells.

PMID- 29446731
TI  - Vitamin D Receptor: A Novel Therapeutic Target for Kidney Diseases.
AB  - BACKGROUND: Kidney disease is a serious problem that adversely affects human
      health, but critical knowledge is lacking on how to effectively treat established
      chronic kidney disease. Mounting evidence from animal and clinical studies has
      suggested that Vitamin D Receptor (VDR) activation has beneficial effects on
      various renal diseases. METHODS: A structured search of published research
      literature regarding VDR structure and function, VDR in various renal diseases
      (e.g., IgA nephropathy, idiopathic nephrotic syndrome, renal cell carcinoma,
      diabetic nephropathy, lupus nephritis) and therapies targeting VDR was performed
      for several databases. RESULT: Included in this study are the results from 177
      published research articles. Evidence from these papers indicates that VDR
      activation is involved in the protection against renal injury in kidney diseases
      by a variety of mechanisms, including suppression of RAS activation, anti
      inflammation, inhibiting renal fibrogenesis, restoring mitochondrial function,
      suppression of autoimmunity and renal cell apoptosis. CONCLUSION: VDR offers an
      attractive druggable target for renal diseases. Increasing our understanding of
      VDR in the kidney is a fertile area of research and may provide effective weapons
      in the fight against kidney diseases.

PMID- 29446736
TI  - Gene Therapy in Kidney Transplantation: Evidence of Efficacy and Future
      Directions.
AB  - Allograft loss remains a severe clinical problem after kidney transplantation.
      The molecular mechanism of graft loss is a complex process involving T and/or B
      cell activation, inflammation responses, autophagy and apoptosis. Since these
      pathways are involved in immune responses in kidney transplant rejection,
      application of genetic interference to inhibit specific pathways could present an
      effective targeted gene therapy method. Recent studies have successfully
      attempted to use gene therapy to target the key molecules involved in immune
      responses during transplantation. This strategy has the potential to silence
      target genes associated with a variety of diseases, including those that trigger
      allograft loss following organ transplantation. In this review, we have discussed
      evidence of the clinical applicability of gene therapy in kidney transplantation
      based on known associations between kidney diseases and genes participating in
      the underlying mechanisms. The molecules contributing to immune responses and
      inflammatory injury are further highlighted as potential targets in future
      clinical therapy for renal transplantation.

PMID- 29446734
TI  - CX3CL1/CX3CR1 Axis, as the Therapeutic Potential in Renal Diseases: Friend or
      Foe?
AB  - The fractalkine receptor chemokine (C-X3-C motif) receptor 1 (CX3CR1) and its
      highly selective ligand CX3CL1 mediate chemotaxis and adhesion of immune cells,
      which are involved in the pathogenesis and progression of numerous inflammatory
      disorders and malignancies. The CX3CL1/CX3CR1 axis has recently drawn attention
      as a potential therapeutic target because it is involved in the ontogeny,
      homeostatic migration, or colonization of renal phagocytes. We performed a
      Medline/PubMed search to detect recently published studies that explored the
      relationship between the CX3CL1/CX3CR1 axis and renal diseases and disorders,
      including diabetic nephropathy, renal allograft rejection, infectious renal
      diseases, IgA nephropathy, fibrotic kidney disease, lupus nephritis and
      glomerulonephritis, acute kidney injury and renal carcinoma. Most studies
      demonstrated its role in promoting renal pathopoiesis; however, several recent
      studies showed that the CX3CL1/CX3CR1 axis could also reduce renal pathopoiesis.
      Thus, the CX3CL1/CX3CR1 axis is now considered to be a double-edged sword that
      could provide novel perspectives into the pathogenesis and treatment of renal
      diseases and disorders.

PMID- 29446737
TI  - Gene-modified Mesenchymal Stem Cell-based Therapy in Renal Ischemia- Reperfusion
      Injury.
AB  - Acute Kidney Injury (AKI) is a common syndrome in the clinic and has become a
      worldwide public health problem. Renal Ischemia-Reperfusion Injury (IRI) is the
      most common cause of AKI. So far, effective treatment is still lacking for renal
      IRI, resulting in a high mortality rate of AKI. Mesenchymal Stem Cells (MSCs),
      considered as a promising candidate for tissue repair and regenerative medicine
      have aroused an increasing concern in recent years for the capacity of self
      renewal and multi-lineage differentiation. MSC-based therapy has drawn wide
      attention for its therapeutic potential in renal IRI. The administrated MSCs can
      alleviate the renal IRI and improve the renal function for its anti-inflammatory,
      immunomodulation properties. MSCs preferentially migrate into injured sites to
      play the role of tissue repair. Furthermore, MSCs can modify the microenvironment
      to promote the recovery of damaged renal tubular cells via paracrine factors.
      However, the poor kidney-directional homing and poor survival under ischemia
      environment have limited their beneficial effects. Genetic modification is an
      effective approach to increase the therapeutic action of MSCs. MSCs are modified
      with exogenous genes to enhance their innate properties. Here we review the
      current knowledge of gene-modified MSCs, their biological characteristics and
      applications in renal IRI.

PMID- 29446738
TI  - How Do Dendritic Cells Play the Role in Ischemia/Reperfusion Triggered Kidney
      Allograft Rejection.
AB  - In deceased donors, Ischemia/Reperfusion Injury (IRI) is an important cause of
      allograft dysfunction. Prolonged cold and warm ischemia time leads to a high risk
      of early post-transplant complications, including acute and chronic rejection.
      Ischemia not only up-regulates inflammatory cytokines and chemokines, but also
      enhances the expression of MHC-class II and adhesion molecules on epithelial and
      dendritic cells. Moreover, the Danger Associated Molecular Patterns (DAMPs)
      released from stressed or dying cells, not only cause or amplify tissue
      inflammation and trigger tissue repair in response to IRI, but also act as
      adjuvants that enhance DC maturation and potentiate the adaptive immune response.
      In this review, we will also discuss about whether donor or recipient DCs are
      more important in the process of ischemia enhanced acute rejection.

PMID- 29446739
TI  - Role of Complement Properdin in Renal Ischemia-Reperfusion Injury.
AB  - Renal Ischemia-Reperfusion Injury (IRI) is one of the main causes of Acute Kidney
      Injury (AKI), and may lead to chronic kidney disease. The high mortality rate of
      AKI has not changed in the last 5 decades due to non-recognition, nephrotoxin
      exposure, delayed diagnosis and lack of specific intervention. Complement
      activation plays important roles in IRI-induced AKI because of its association
      with immunity, inflammation, cell death and tissue repair. Nevertheless, the role
      of complement properdin, the sole positive regulator of the alternative pathway,
      in IRI-induced AKI has not been well defined. This review evaluates the dynamic
      changes and underlying mechanisms of complement activation with a focus on
      properdin in both in vitro and in vivo models challenged by hypoxia/
      reoxygenation and renal IRI. The multiple actions of properdin associated with
      HMGB1 and caspase-3, apoptosis and inflammation mediators, are discussed in the
      context of immunity, injury and repair at both the early and later stages of AKI.
      The complement activation-independent role of properdin and the effect of
      modulating properdin with or without genotype alteration are also addressed.
      Taking together, these might provide new mechanistic insights that potentially
      benefit timely diagnosis and specific intervention of IRI-induced AKI.

PMID- 29446740
TI  - Role of Immune Cells in Diabetic Kidney Disease.
AB  - Diabetic Kidney Disease (DKD) is one of the major complications of Diabetes
      Mellitus (DM) and is currently the most common cause of End-Stage Renal Disease
      (ESRD) worldwide. Traditionally, DKD is considered a disease which has nothing to
      do with the immune system, and the pathogenesis is mainly characterized to be
      metabolic disturbance. Recent growing evidence indicates immunologic and
      inflammatory mechanisms in the development and progression of DKD. This overview
      of macrophages, dendritic cells, T lymphocytes, B lymphocytes, neutrophils and
      mast cells is closely involved in the pathologic process of DKD, with more
      emphasis on the leucocyte accumulation and related molecular mechanisms.
      Moreover, the potential contributions of these immune cells to renal injury will
      also be discussed. Specifically, these findings help to identify new potential
      therapeutic targets of DKD. Future preclinical and clinical studies might
      translate these exciting findings into clinical applications.

PMID- 29446741
TI  - What's new in Gene Therapy of Hemophilia.
AB  - BACKGROUND: Several methods have been investigated to effectively and safely
      transmit genes that stimulate cells to release therapeutic factor VIII (FVIII)
      and factor IX (FIX) into the circulation of people with hemophilia (PWH).
      OBJECTIVE: To review the role of gene therapy (GT) in PWH. METHODS: A Cochrane
      Library and PubMed (MEDLINE) search related to the role of GT in hemophilia was
      analyzed. RESULTS: The most promising vectors for hemophilia GT are adeno
      associated virus (AAV) and lentivirus. Several gene methods are available to
      lessen risks related to random vector integration and insertional mutagenesis,
      based on designer nucleases or CRISPR/Cas9 (clustered regularly interspaced short
      palindromic repeats/CRISPR associated system). However, off-target issues need to
      be more meticulously and widely evaluated. Some clinical studies on hemophilia B
      based on AAV have obtained transitory or subtherapeutic levels of FIX expression.
      Another problem is possible transitory liver toxicity. Therefore, to reduce
      unintentional immune responses, transitory immunosuppression must be used,
      particularly when administering high-vector doses. Codon-optimized FVIII or FIX
      transgenes are able to promote clotting factor expression levels. The inclusion
      of a hyper-active gain-of-function R338L mutation in the FIX gene (FIX-R338L [FIX
      Padua]) makes the procedure more effective. CONCLUSION: Achieving a safe and
      efficient remedy for hemophilia A and B by means of GT vector engineering needs
      further improvement. No randomized or quasi-randomized clinical trials of GT for
      hemophilia have been found. Given it is in its incipient period, there is need
      for well-designed clinical trials to evaluate the long-term practicability,
      efficacy and risks of GT for PWH.

PMID- 29446742
TI  - Development of an In-vitro Drug Delivery Efficiency Test for a Pulmonary
      Toxicokinetic Pig Study.
AB  - BACKGROUND: Since their appearance on the drugs of abuse market, synthetic
      cannabinoids (SCs) are gaining increasing toxicological relevance. They are
      consumed without knowledge of their toxicokinetic (TK) and toxicodynamic
      properties and human studies are not allowed due to ethical reasons. A controlled
      animal TK study following nebulization of 4-ethylnaphthalene-1-yl-(1-pentylindole
      3-yl)methanone (JWH-210), 2-(4-methoxyphenyl)-1-(1-pentyl-indole-3-yl)methanone
      (RCS-4) as well as Delta9-tetrahydrocannabinol (THC) to pigs should be helpful
      for better interpretation of analytical results in cases of misuse or poisoning.
      As a prerequisite, an in-vitro test system mimicking a ventilated pig had to be
      developed to determine the quantity and reproducibility of which drug dose is
      delivered to the pig lung. METHODS: JWH-210, RCS-4, and THC (1 mg in 2 mL ethanol
      each) were nebulized during ventilation using an ultrasonic nebulizer. The drug
      aerosol was delivered via the inspiratory limb and the endotracheal tube passing
      through a glass fiber filter (n = 6). The drugs were extracted from the filters
      using ethanol and ultrasonication. After several dilution steps and adding an
      internal standard solution, the extracts were analyzed by LC-MS/MS. RESULTS:
      Extraction of the nebulized drugs revealed delivery efficiencies of 78.8 +/- 5.0%
      for JWH-210, 70.5 +/- 6.9% for RCS-4, and 70.8 +/- 7.9% for THC. The loss of
      about 20-30% of the administered dose might be attributable to retention in the
      nebulizer device or adhesion of the aerosol particles to the tube wall.
      CONCLUSION: Nevertheless, regarding delivery efficiencies, the minor standard
      deviations indicate an acceptable reproducibility, suggesting that this
      administration system is suitable for application in TK studies.

PMID- 29446743
TI  - Recent Advances in Antioxidant Cosmeceutical Topical Delivery.
AB  - Antioxidants are among the most important cosmeceuticals, with proven ability of
      inhibiting cellular damage. The topical skin administration of antioxidants is
      essential for minimizing skin aging and achieving better skin protection against
      harmful free radicals. However, their unfavorable physiochemical properties such
      as chemical instability, excessive hydrophilicity or lipophilicity and others
      could be a great obstacle against their skin promising effects as well as their
      delivery to deeper skin layers. These problems could all be remedied through the
      use of delivery carriers. The present review discusses the various delivery
      carriers which were proven successful in improving the beneficial effects of
      antioxidants against skin aging, namely different vesicular systems, lipidic
      systems, polymeric systems and carbon nanotubes, and their applications in
      topical antioxidant delivery.

PMID- 29446744
TI  - Delivery of Peptidic Gonadotropin Releasing Hormone Antagonists.
AB  - GnRH antagonists have several clinical applications in prostate cancer,
      regulation of ovulation induction in females, breast cancer, male contraception
      and others. Antagonists differ from natural GnRH decapeptide in having five or
      more amino acid substitutions, whereas most of the antagonists are available as
      subcutaneous (SC) formula for injection some are formulated as a depot
      formulation for sustained release (e.g., Cetrorelix, Degarelix). Systemic
      delivery of cetrorelix acetate by intratracheal route can be achieved using dry
      powder for inhalation of the adhesive mixture when the powder deposition reaches
      stage four. The oral route for systemic delivery of peptide without its
      degradation can be achieved using gastrointestinal permeation enhancement
      technology GIPET(r) provided by acyline.

PMID- 29446746
TI  - Mechanisms involved in glycemic control promoted by exercise in diabetics.
AB  - INTRODUCTION: Diabetes mellitus is a metabolic disease characterized by high
      glycemic levels for long periods. This disease has a high prevalence in the world
      population, being currently observed an increase in its incidence. This fact is
      mainly due to the sedentary lifestyle and hypercaloric diets. Non-pharmacological
      interventions for glycemic control include exercise, which promotes changes in
      skeletal muscle and adipocytes. Thus, increased glucose uptake by skeletal muscle
      and decreased insulin resistance through modulating adipocytes are the main
      factors that improve glycemic control against diabetes. Conclusio: it was sought
      to elucidate mechanisms involved in the improvement of glycemic control in
      diabetics in front of the exercise.

PMID- 29446745
TI  - Editorial: Nailfold Capillaroscopy in Rheumatology.

PMID- 29446747
TI  - CRISPR/Cas9 Genome Editing: A Promising Tool for Therapeutic Applications of
      Induced Pluripotent Stem Cells.
AB  - BACKGROUND: Induced pluripotent stem cells hold tremendous potential for
      biological and therapeutic applications. The development of efficient
      technologies for targeted genome alteration of stem cells in disease models is a
      prerequisite for utilizing stem cells to their full potential. The revolutionary
      technology for genome editing known as the clustered regularly interspaced short
      palindromic repeat (CRISPR)-associated protein 9 (Cas9) system is recently
      recognized as a powerful tool for editing DNA at specific loci. OBJECTIVE: The
      ease of use of the CRISPR-Cas9 technology will allow us to improve our
      understanding of genomic variation in disease processes via cellular and animal
      models. More recently, this system was modified to repress (CRISPR interference,
      CRISPRi) or activate (CRISPR activation, CRISPRa) gene expression without
      alterations in the DNA, which amplified the scope of applications of CRISPR
      systems for stem cell biology. RESULTS AND CONCLUSION: Here, we highlight latest
      advances of CRISPR-associated applications in human pluripotent stem cells. The
      challenges and future prospects of CRISPR-based systems for human research are
      also discussed.

PMID- 29446749
TI  - The seroprevalence of cystic echinococcosis in a rural normal population,
      southwestern Iran.
AB  - INTRODUCTION: Cystic echinococcosis is a neglected zoonotic disease with
      worldwide distribution, which occurs mainly in pastoral regions. Echinococcus
      granulosus sensu stricto, is the main agent of human infection. Although Iran is
      an endemic area for CE in the Middle East, lack of data regarding the disease
      among rural inhabitants of Khuzestan province in recent years, persuaded us to
      perform the current study. METHODOLOGY: This cross-sectional study was conducted
      in 2016 using simple random sampling method in 15 villages of Shushtar county,
      southwestern Iran. Three hundred and fourteen of rural inhabitants were examined
      using AgB- ELISA test for CE. RESULTS: From the 314 patients included in the
      study, females and males were 244 (77.7%) and 70 (22.3%), respectively. Of these,
      227 (72.3%) were in close contact with dogs, which 173 (70.9%) of them were
      females and 54 (29.1%) were males. ELISA detected three (1%) seropositive cases
      among investigated population. All three positive cases were females and in close
      contact with dogs. Furthermore, the positive cases in the age range of 21-50.
      None of the 70 examined males were positive. CONCLUSIONS: This study is the first
      report of CE in rural areas of Shushtar, Southwest Iran, which indicated
      seroprevalence of CE among rural areas with high prevalence rate of infection
      among females. It seems that the rural population of the region are at the risk
      of exposure to E. granulosus eggs. Therefore, more studies are required to
      evaluate the human CE in all parts of the province using serological and
      ultrasound methods.

PMID- 29446748
TI  - Anti-Oxidants as Chemopreventive Agents in Prostate Cancer: A Gap Between
      Preclinical and Clinical Studies.
AB  - BACKGROUND: Tumor cells may be expressed as a result of oxidative stress. The
      extent of oxidative stress correlates with the aggressive and metastatic potency
      of cancer. OBJECTIVE: One simple way to control prostate cancer is through
      chemoprevention which refers to the administration of natural or synthetic agents
      to block, reverse, or delay the process of carcinogenesis. The most
      chemopreventive agents are antioxidants in nature. METHODS: In this review, we
      summarized the effects of dietary antioxidants with a focus on their molecular
      mechanisms and possible roles in the treatment of prostate cancer cells. We also
      reported the recent outcomes of laboratory and/or clinical trials of antioxidants
      in prostate cancer patients. RESULTS: Numerous pre-clinical studies showed that
      antioxidants protect DNA against being damaged by Reactive Oxygen Species (ROS),
      thereby genetic mutations causing cancer are likely to be prevented. However, the
      clinical trial results showed that antioxidants have yielded mixed outcomes or
      benefitted only a subgroup of the population. CONCLUSION: A greater understanding
      of the molecular events associated with antioxidants will enhance the development
      of treatment and could result in better strategies for the chemoprevention of
      prostate cancer. Recent patents also suggest that anti-oxidant compounds can be
      effective for the prevention and the treatment of prostate cancer.

PMID- 29446750
TI  - Copaiba Oil Decreases Oxidative Stress and Inflammation But not Colon Damage in
      Rats with TNBS-Induced Colitis.
AB  - BACKGROUND: TNBS-induced colitis is an experimental immunopathology in rats that
      shares many features with human inflammatory bowel diseases. Copaiba oleoresin is
      extracted from plants of the genus Copaifera and is shown to reduce inflammation.
      OBJECTIVE: The aim of this study was to investigate the action of copaiba oil (C.
      reticulata Ducke) on inflammation and oxidative status in the distal colon of
      colitic rats. METHODS: Acute and subchronic colitis were induced in Wistar rats
      by an intracolonic enema with 2,4,6-trinitrobenzenesulfonic acid (TNBS). The
      colonic morphology was assessed by histological analysis and the oxidative stress
      parameters were measured in the intestinal homogenate. The liver damage markers
      were measured in the plasma. Control and colitic rats were orally treated either
      with one single dose (acute colitis) of copaiba oil (1.15 g Kg-1) or once a day
      during seven days (subchronic colitis). RESULTS: The intestinal morphology was
      severely modified by acute and subchronic colitis, as indicated by the intramural
      infiltration of polymorphonuclear cells and the increased thickness of all colon
      layers. The levels of TBARS, protein carbonyl groups and reactive oxygen species
      (ROS) were increased in the intestine of colitic rats. Copaiba oil did not
      attenuate the inflammatory damage in acute and subchronic colitis, but it
      decreased the activity of myeloperoxidase, leukocyte infiltration and oxidative
      stress in the colon. The level of plasma bilirubin and the activity of alkaline
      phosphatase were both increased in treated healthy and colitic rats. CONCLUSION:
      Copaiba oil decreased oxidative stress and inflammation but did not prevent
      intestinal damage in the colon of colitic rats. The alterations of plasma markers
      of hepatic damage caused by the oil seem to be associated to its harmful action
      on the liver.

PMID- 29446751
TI  - Molecular mechanism to target the endosomal Mon1-Ccz1 GEF complex to the pre
      autophagosomal structure.
AB  - During autophagy, a newly formed double membrane surrounds its cargo to generate
      the so-called autophagosome, which then fuses with a lysosome after closure.
      Previous work implicated that endosomal Rab7/Ypt7 associates to autophagosomes
      prior to their fusion with lysosomes. Here, we unravel how the Mon1-Ccz1
      guanosine exchange factor (GEF) acting upstream of Ypt7 is specifically recruited
      to the pre-autophagosomal structure under starvation conditions. We find that
      Mon1-Ccz1 directly binds to Atg8, the yeast homolog of the members of the
      mammalian LC3 protein family. This requires at least one LIR motif in the Ccz1 C
      terminus, which is essential for autophagy but not for endosomal transport. In
      agreement, only wild-type, but not LIR-mutated Mon1-Ccz1 promotes Atg8-dependent
      activation of Ypt7. Our data reveal how GEF targeting can specify the fate of a
      newly formed organelle and provide new insights into the regulation of
      autophagosome-lysosome fusion.

PMID- 29446753
TI  - Correction: Measurements and models of electric fields in the in vivo human brain
      during transcranial electric stimulation.

PMID- 29446752
TI  - Allosteric mechanism of the V. vulnificus adenine riboswitch resolved by four
      dimensional chemical mapping.
AB  - The structural interconversions that mediate the gene regulatory functions of RNA
      molecules may be different from classic models of allostery, but the relevant
      structural correlations have remained elusive in even intensively studied
      systems. Here, we present a four-dimensional expansion of chemical mapping called
      lock-mutate-map-rescue (LM2R), which integrates multiple layers of mutation with
      nucleotide-resolution chemical mapping. This technique resolves the core
      mechanism of the adenine-responsive V. vulnificus add riboswitch, a paradigmatic
      system for which both Monod-Wyman-Changeux (MWC) conformational selection models
      and non-MWC alternatives have been proposed. To discriminate amongst these
      models, we locked each functionally important helix through designed mutations
      and assessed formation or depletion of other helices via compensatory rescue
      evaluated by chemical mapping. These LM2R measurements give strong support to the
      pre-existing correlations predicted by MWC models, disfavor alternative models,
      and suggest additional structural heterogeneities that may be general across
      ligand-free riboswitches.

PMID- 29446754
TI  - Highly polarization sensitive photodetectors based on quasi-1D titanium
      trisulfide (TiS3).
AB  - Photodetectors with high polarization sensitivity are in great demand in advanced
      optical communication. Here, we demonstrate that photodetectors based on titanium
      trisulfide (TiS3) are extremely sensitive to polarized light (from visible to the
      infrared), due to its reduced in-plane structural symmetry. By density functional
      theory calculation, TiS3 has a direct bandgap of 1.13 eV. The highest
      photoresponsivity reaches 2500 A W-1. What is more, in-plane optical selection
      caused by strong anisotropy leads to the photoresponsivity ratio for different
      directions of polarization that can reach 4:1. The angle-dependent photocurrents
      of TiS3 clearly display strong linear dichroism. Moreover, the Raman peak at 370
      cm-1 is also very sensitive to the polarization direction. The theoretical
      optical absorption of TiS3 is calculated by using the HSE06 hybrid functional
      method, in qualitative agreement with the observed experimental
      photoresponsivity.

PMID- 29446755
TI  - Classification methods to detect sleep apnea in adults based on respiratory and
      oximetry signals: a systematic review.
AB  - OBJECTIVE: Sleep apnea (SA), a common sleep disorder, can significantly decrease
      the quality of life, and is closely associated with major health risks such as
      cardiovascular disease, sudden death, depression, and hypertension. The normal
      diagnostic process of SA using polysomnography is costly and time consuming. In
      addition, the accuracy of different classification methods to detect SA varies
      with the use of different physiological signals. If an effective, reliable, and
      accurate classification method is developed, then the diagnosis of SA and its
      associated treatment will be time-efficient and economical. This study aims to
      systematically review the literature and present an overview of classification
      methods to detect SA using respiratory and oximetry signals and address the
      automated detection approach. APPROACH: Sixty-two included studies revealed the
      application of single and multiple signals (respiratory and oximetry) for the
      diagnosis of SA. MAIN RESULTS: Both airflow and oxygen saturation signals alone
      were effective in detecting SA in the case of binary decision-making, whereas
      multiple signals were good for multi-class detection. In addition, some machine
      learning methods were superior to the other classification methods for SA
      detection using respiratory and oximetry signals. SIGNIFICANCE: To deal with the
      respiratory and oximetry signals, a good choice of classification method as well
      as the consideration of associated factors would result in high accuracy in the
      detection of SA. An accurate classification method should provide a high
      detection rate with an automated (independent of human action) analysis of
      respiratory and oximetry signals. Future high-quality automated studies using
      large samples of data from multiple patient groups or record batches are
      recommended.

PMID- 29446756
TI  - Plasmon-enhanced scattering and charge transfer in few-layer graphene interacting
      with buried printed 2D-pattern of silver nanoparticles.
AB  - Hybrid structures combing silver nanoparticles and few-layer graphene have been
      synthetized by combining low-energy ion beam synthesis and stencil techniques. A
      single plane of metallic nanoparticles plays the role of an embedded plasmonic
      enhancer located in dedicated areas at a controlled nanometer distance from
      deposited graphene layers. Optical imaging, reflectance and Raman scattering
      mapping are used to measure the enhancement of electronic and vibrational
      properties of these layers. In particular electronic Raman scattering is shown as
      notably efficient to analyze the optical transfer of charge carriers between the
      systems and the presence of intrinsic and extrinsic defects.

PMID- 29446757
TI  - 3D bioprinting mesenchymal stem cell-laden construct with core-shell nanospheres
      for cartilage tissue engineering.
AB  - Cartilage tissue is prone to degradation and has little capacity for self-healing
      due to its avascularity. Tissue engineering, which provides artificial scaffolds
      to repair injured tissues, is a novel and promising strategy for cartilage
      repair. 3D bioprinting offers even greater potential for repairing degenerative
      tissue by simultaneously integrating living cells, biomaterials, and biological
      cues to provide a customized scaffold. With regard to cell selection, mesenchymal
      stem cells (MSCs) hold great capacity for differentiating into a variety of cell
      types, including chondrocytes, and could therefore be utilized as a cartilage
      cell source in 3D bioprinting. In the present study, we utilize a tabletop
      stereolithography-based 3D bioprinter for a novel cell-laden cartilage tissue
      construct fabrication. Printable resin is composed of 10% gelatin methacrylate
      (GelMA) base, various concentrations of polyethylene glycol diacrylate (PEGDA),
      biocompatible photoinitiator, and transforming growth factor beta 1 (TGF-beta1)
      embedded nanospheres fabricated via a core-shell electrospraying technique. We
      find that the addition of PEGDA into GelMA hydrogel greatly improves the printing
      resolution. Compressive testing shows that modulus of the bioprinted scaffolds
      proportionally increases with the concentrations of PEGDA, while swelling ratio
      decreases with the increase of PEGDA concentration. Confocal microscopy images
      illustrate that the cells and nanospheres are evenly distributed throughout the
      entire bioprinted construct. Cells grown on 5%/10% (PEGDA/GelMA) hydrogel present
      the highest cell viability and proliferation rate. The TGF-beta1 embedded in
      nanospheres can keep a sustained release up to 21 d and improve chondrogenic
      differentiation of encapsulated MSCs. The cell-laden bioprinted cartilage
      constructs with TGF-beta1-containing nanospheres is a promising strategy for
      cartilage regeneration.

PMID- 29446758
TI  - Localized thin-section CT with radiomics feature extraction and machine learning
      to classify early-detected pulmonary nodules from lung cancer screening.
AB  - Lung cancer screening aims to detect small pulmonary nodules and decrease the
      mortality rate of those affected. However, studies from large-scale clinical
      trials of lung cancer screening have shown that the false-positive rate is high
      and positive predictive value is low. To address these problems, a technical
      approach is greatly needed for accurate malignancy differentiation among these
      early-detected nodules. We studied the clinical feasibility of an additional
      protocol of localized thin-section CT for further assessment on recalled patients
      from lung cancer screening tests. Our approach of localized thin-section CT was
      integrated with radiomics features extraction and machine learning classification
      which was supervised by pathological diagnosis. Localized thin-section CT images
      of 122 nodules were retrospectively reviewed and 374 radiomics features were
      extracted. In this study, 48 nodules were benign and 74 malignant. There were
      nine patients with multiple nodules and four with synchronous multiple malignant
      nodules. Different machine learning classifiers with a stratified ten-fold cross
      validation were used and repeated 100 times to evaluate classification accuracy.
      Of the image features extracted from the thin-section CT images, 238 (64%) were
      useful in differentiating between benign and malignant nodules. These useful
      features include CT density (p  =  0.002 518), sigma (p  =  0.002 781),
      uniformity (p  =  0.032 41), and entropy (p  =  0.006 685). The highest
      classification accuracy was 79% by the logistic classifier. The performance
      metrics of this logistic classification model was 0.80 for the positive
      predictive value, 0.36 for the false-positive rate, and 0.80 for the area under
      the receiver operating characteristic curve. Our approach of direct risk
      classification supervised by the pathological diagnosis with localized thin
      section CT and radiomics feature extraction may support clinical physicians in
      determining truly malignant nodules and therefore reduce problems in lung cancer
      screening.

PMID- 29446759
TI  - Photoelastic colloidal gel for a high-sensitivity strain sensor.
AB  - Nanoparticles, having the ability to self-assemble into an ordered structure in
      their suspensions, analogous to liquid crystals, have attracted extensive
      attention. Herein, we report a new type of colloidal gel with an ordered crystal
      structure assembled from 1D and 2D nanoparticles. The material has high
      elasticity and, more interestingly, it shows significant photoelasticity. Its
      refractive index can be tuned under external stress and exhibits an ultra-wide
      dynamic range (Deltan) of the order of 10-2. Due to the large Deltan, the
      material shows an extremely high strain sensibility of 720 nm/epsilon, an order
      of magnitude higher than the reported ones.

PMID- 29446760
TI  - Quenching-free fluorescence signal from plastic-fibres in proton dosimetry:
      understanding the influence of Cerenkov radiation.
AB  - The origin of photons emitted in optical fibres under proton irradiation has been
      attributed to either entirely Cerenkov radiation or light consisting of
      fluorescence with a substantial amount of Cerenkov radiation. The source of the
      light emission is assessed in order to understand why the signal from optical
      fibres irradiated with protons is reportedly quenching-free. The present study
      uses the directional emittance of Cerenkov photons in 12 MeV and 20 MeV electron
      beams to validate a Monte Carlo model for simulating the emittance and
      transmission of Cerenkov radiation in optical fibres. We show that fewer than
      0.01 Cerenkov photons are emitted and guided per 225 MeV proton penetrating the
      optical fibre, and that the Cerenkov signal in the optical fibre is completely
      negligible at the Bragg peak. Furthermore, on taking the emittance and guidance
      of both fluorescence and Cerenkov photons into account, it becomes evident that
      the reported quenching-free signal in PMMA-based optical fibres during proton
      irradiation is due to fluorescence.

PMID- 29446761
TI  - 3D printed stretchable capacitive sensors for highly sensitive tactile and
      electrochemical sensing.
AB  - Developments of innovative strategies for the fabrication of stretchable sensors
      are of crucial importance for their applications in wearable electronic systems.
      In this work, we report the successful fabrication of stretchable capacitive
      sensors using a novel 3D printing method for highly sensitive tactile and
      electrochemical sensing applications. Unlike conventional lithographic or
      templated methods, the programmable 3D printing technique can fabricate complex
      device structures in a cost-effective and facile manner. We designed and
      fabricated stretchable capacitive sensors with interdigital and double-vortex
      designs and demonstrated their successful applications as tactile and
      electrochemical sensors. Especially, our stretchable sensors exhibited a
      detection limit as low as 1 * 10-6 M for NaCl aqueous solution, which could have
      significant potential applications when integrated in electronics skins.

PMID- 29446762
TI  - Investigation of growth parameters influence on self-catalyzed ITO nanowires by
      high RF-power sputtering.
AB  - ITO nanowires have been successfully fabricated using a radio-frequency
      sputtering technique with a high RF-power of 250W. The fabrication of the ITO
      nanowires has been optimized through the study of oxygen flow rates, temperatures
      and RF-power. The difference in the morphology of the ITO nanowires prepared by
      using a new target and a used target has been first observed and the mechanism
      for the difference has been discussed in detail. A hollow structure and air voids
      within the nanowires are formed during the process of the nanowire growth. The
      ITO nanowires fabricated by this method has demonstrated good conductivity
      (15Omega/sq) and a transmittance of more than 64% at a wavelength longer than
      550nm after annealing. Furthermore, detailed microstructure studies show that the
      ITO nanowires exhibit a large number of oxygen vacancies. As a result, it is
      expected that they can be useful for the fabrication of gas sensor devices.

PMID- 29446763
TI  - Ferroelectric nanoparticle-embedded sponge structure triboelectric generators.
AB  - We report high-performance triboelectric nanogenerators (TENGs) employing
      ferroelectric nanoparticles (NPs) embedded in a sponge structure. The
      ferroelectric BaTiO3 NPs inside the sponge structure play an important role in
      increasing surface charge density by polarized spontaneous dipoles, enabling the
      packaging of TENGs even with a minimal separation gap. Since the friction
      surfaces are encapsulated in the packaged device structure, it suffers negligible
      performance degradation even at a high relative humidity of 80%. The TENGs also
      demonstrated excellent mechanical durability due to the elasticity and
      flexibility of the sponge structure. Consequently, the TENGs can reliably harvest
      energy even under harsh conditions. The approach introduced here is a simple,
      effective, and reliable way to fabricate compact and packaged TENGs for potential
      applications in wearable energy-harvesting devices.

PMID- 29446764
TI  - Antibodies against glycoprotein 2 display diagnostic advantages over ASCA in
      distinguishing CD from intestinal tuberculosis and intestinal Behcet's disease.
AB  - OBJECTIVES: There is an increasing need to identify reliable biomarkers for
      distinguishing Crohn's disease (CD) from other gastrointestinal disorders sharing
      similar clinical and pathological features. This study aimed at evaluating the
      diagnostic potential of antibodies to zymogen granule glycoprotein GP2 (aGP2) in
      a large, well-defined Chinese cohort with a special focus on their role in
      discriminating CD from intestinal Behcet's disease (BD) and intestinal
      tubercolosis (ITB). METHODS: A total of 577 subjects were prospectively enrolled,
      including 171 patients with CD, 208 patients with ulcerative colitis (UC), 71
      with BD, 57 with ITB and 70 healthy controls (HC). aGP2 and anti-Saccharomyces
      cerevisiae antibodies (ASCA) were determined by ELISA. Perinuclear antineutrophil
      cytoplasmic antibodies were tested by indirect immunofluorescent assay. RESULTS:
      aGP2 IgG and IgA levels were significantly elevated in patients with CD compared
      with those in patients with UC, intestinal BD, and ITB and HC. Conversely, ASCA
      IgG levels were not different between CD and intestinal BD patients, whereas ASCA
      IgA levels did not discriminate CD from intestinal BD and ITB patients. aGP2 IgA
      and IgG displayed a better assay performance (larger areas under the curve) over
      ASCA IgA and IgG in differentiating CD from disease controls (P<0.05). ASCA IgA
      did not discriminate CD from disease controls. aGP2 IgA and/or IgG was
      significantly associated with penetrating disease (B3) and ileal CD (L1)
      (P<0.05), whereas ASCA IgA and/or IgG was not. CONCLUSIONS: In comparison with
      ASCA, aGP2 distinguishes CD from intestinal BD or ITB as disease controls more
      efficiently, aiding in the differential diagnosis of IBD.

PMID- 29446766
TI  - Are whole-exome and whole-genome sequencing approaches cost-effective? A
      systematic review of the literature.
AB  - PURPOSE: We conducted a systematic literature review to summarize the current
      health economic evidence for whole-exome sequencing (WES) and whole-genome
      sequencing (WGS). METHODS: Relevant studies were identified in the EMBASE,
      MEDLINE, Cochrane Library, EconLit and University of York Centre for Reviews and
      Dissemination databases from January 2005 to July 2016. Publications were
      included in the review if they were economic evaluations, cost studies, or
      outcome studies. RESULTS: Thirty-six studies met our inclusion criteria. These
      publications investigated the use of WES and WGS in a variety of genetic
      conditions in clinical practice, the most common being neurological or
      neurodevelopmental disorders. Study sample size varied from a single child to
      2,000 patients. Cost estimates for a single test ranged from $555 to $5,169 for
      WES and from $1,906 to $24,810 for WGS. Few cost analyses presented data
      transparently and many publications did not state which components were included
      in cost estimates. CONCLUSION: The current health economic evidence base to
      support the more widespread use of WES and WGS in clinical practice is very
      limited. Studies that carefully evaluate the costs, effectiveness, and cost
      effectiveness of these tests are urgently needed to support their translation
      into clinical practice.

PMID- 29446765
TI  - Gut Microbiota-Based Therapies for Irritable Bowel Syndrome.
AB  - Irritable bowel syndrome (IBS) is a common, heterogeneous disorder characterized
      by abdominal pain associated with changes in bowel habits. The pathogenesis of
      IBS is multifactorial and may relate to alterations in the gut microbiota,
      changes in visceral sensation and motility, and genetic and environmental
      factors. Administration of systemic antibiotics may increase the risk of IBS by
      altering gastrointestinal homeostasis. Therapeutic interventions for IBS with
      diarrhea that are thought to target alterations in the gut microbiota include the
      nonsystemic antibiotic rifaximin, the medical food serum-derived bovine
      immunoglobulin, prebiotics, probiotics, and dietary modification. SYN-010 is a
      modified-release statin formulation that reduces methane production by
      Methanobrevibacter smithii and is currently in development for the treatment of
      patients with constipation-predominant IBS. Use of these interventions in the
      management of patients with IBS may function to restore a healthy gut microbiota
      and ameliorate symptoms of IBS.

PMID- 29446768
TI  - Vascular cognitive impairment.

PMID- 29446769
TI  - Vascular cognitive impairment.
AB  - The term vascular cognitive impairment (VCI) was introduced around the start of
      the new millennium and refers to the contribution of vascular pathology to any
      severity of cognitive impairment, ranging from subjective cognitive decline and
      mild cognitive impairment to dementia. Although vascular pathology is common in
      elderly individuals with cognitive decline, pure vascular dementia (that is,
      dementia caused solely by vascular pathology) is uncommon. Indeed, most patients
      with vascular dementia also have other types of pathology, the most common of
      which is Alzheimer disease (specifically, the diffuse accumulation of amyloid
      beta plaques and neurofibrillary tangles composed of tau). At present, the main
      treatment for VCI is prevention by treating vascular diseases and other risk
      factors for VCI, such as hypertension and diabetes mellitus. Despite the current
      paucity of disease-modifying pharmacological treatments, we foresee that
      eventually, we might be able to target specific brain diseases to prevent
      cognitive decline and dementia.

PMID- 29446767
TI  - CLAPO syndrome: identification of somatic activating PIK3CA mutations and
      delineation of the natural history and phenotype.
AB  - PURPOSE: CLAPO syndrome is a rare vascular disorder characterized by capillary
      malformation of the lower lip, lymphatic malformation predominant on the face and
      neck, asymmetry, and partial/generalized overgrowth. Here we tested the
      hypothesis that, although the genetic cause is not known, the tissue distribution
      of the clinical manifestations in CLAPO seems to follow a pattern of somatic
      mosaicism. METHODS: We clinically evaluated a cohort of 13 patients with CLAPO
      and screened 20 DNA blood/tissue samples from 9 patients using high-throughput,
      deep sequencing. RESULTS: We identified five activating mutations in the PIK3CA
      gene in affected tissues from 6 of the 9 patients studied; one of the variants
      (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in
      developmental disorders. CONCLUSION: We describe for the first time the presence
      of somatic activating PIK3CA mutations in patients with CLAPO. We also report an
      update of the phenotype and natural history of the syndrome.

PMID- 29446770
TI  - Biomarkers: Extended predictive value of d-dimer.

PMID- 29446771
TI  - Basic research: Epigenetic map of heart development and disease.

PMID- 29446772
TI  - Production of ready-to-use few-layer graphene in aqueous suspensions.
AB  - Graphene has promising physical and chemical properties such as high strength and
      flexibility, coupled with high electrical and thermal conductivities. It is
      therefore being incorporated into polymer-based composites for use in electronics
      and photonics applications. A main constraint related to the graphene development
      is that, being of a strongly hydrophobic nature, almost all dispersions (usually
      required for its handling and processing toward the desired application) are
      prepared in poisonous organic solvents such as N-methyl pyrrolidone or N,N
      dimethyl formamide. Here, we describe how to prepare exfoliated graphite using a
      ball mill. The graphene produced is three to four layers thick and ~500 nm in
      diameter on average, as measured by electron microscopy and Raman spectroscopy;
      can be stored in the form of light solid; and is easily dispersed in aqueous
      media. Our methodology consists of four main steps: (i) the mechanochemical
      intercalation of organic molecules (melamine) into graphite, followed by
      suspension in water; (ii) the washing of suspended graphene to eliminate most of
      the melamine; (iii) the isolation of stable graphene sheets; and (iv) freeze
      drying to obtain graphene powder. This process takes 6-7 or 9-10 d for aqueous
      suspensions and dry powders, respectively. The product has well-defined
      properties and can be used for many science and technology applications,
      including toxicology impact assessment and the production of innovative medical
      devices.

PMID- 29446773
TI  - An experimental toolbox for characterization of mammalian collagen type I in
      biological specimens.
AB  - Collagen type I is the most abundant extracellular matrix protein, and collagen
      type I supramolecular assemblies (e.g., tissue grafts, biomaterials and cell
      assembled systems) are used extensively in tissue engineering and regenerative
      medicine. Many studies, for convenience or economic reasons, do not accurately
      determine collagen type I purity, concentration, solubility and extent of cross
      linking in biological specimens, frequently resulting in erroneous conclusions.
      In this protocol, we describe solubility; normal, reduced and delayed
      (interrupted) SDS-PAGE; hydroxyproline; Sircol collagen and Pierce BCA protein;
      denaturation temperature; ninhydrin/trinitrobenzene sulfonic acid; and
      collagenase assays and assess them in a diverse range of biological samples
      (e.g., tissue samples; purified solutions or lyophilized materials; 3D scaffolds,
      such as sponges and hydrogels; and cell media and layers). Collectively, the
      described protocols provide a comprehensive, yet fast and readily implemented,
      toolbox for collagen type I characterization in any biological specimen.

PMID- 29446774
TI  - Proteome-wide identification of ubiquitin interactions using UbIA-MS.
AB  - Ubiquitin-binding proteins play an important role in eukaryotes by translating
      differently linked polyubiquitin chains into proper cellular responses. Current
      knowledge about ubiquitin-binding proteins and ubiquitin linkage-selective
      interactions is mostly based on case-by-case studies. We have recently reported a
      method called ubiquitin interactor affinity enrichment-mass spectrometry (UbIA
      MS), which enables comprehensive identification of ubiquitin interactors for all
      ubiquitin linkages from crude cell lysates. One major strength of UbIA-MS is the
      fact that ubiquitin interactors are enriched from crude cell lysates, in which
      proteins are present at endogenous levels, contain biologically relevant post
      translational modifications (PTMs) and are assembled in native protein complexes.
      In addition, UbIA-MS uses chemically synthesized nonhydrolyzable diubiquitin,
      which mimics native diubiquitin and is inert to cleavage by endogenous
      deubiquitinases (DUBs). Here, we present a detailed protocol for UbIA-MS that
      proceeds in five stages: (i) chemical synthesis of ubiquitin precursors and click
      chemistry for the generation of biotinylated nonhydrolyzable diubiquitin baits,
      (ii) in vitro affinity purification of ubiquitin interactors, (iii) on-bead
      interactor digestion, (iv) liquid chromatography (LC)-MS/MS analysis and (v) data
      analysis to identify differentially enriched proteins. The computational analysis
      tools are freely available as an open-source R software package, including a
      graphical interface. Typically, UbIA-MS allows the identification of dozens to
      hundreds of ubiquitin interactors from any type of cell lysate, and can be used
      to study cell type or stimulus-dependent ubiquitin interactions. The
      nonhydrolyzable diubiquitin synthesis can be completed in 3 weeks, followed by
      ubiquitin interactor enrichment and identification, which can be completed within
      another 2 weeks.

PMID- 29446775
TI  - Carbon dots with efficient solid-state red-light emission through the step-by
      step surface modification towards light-emitting diodes.
AB  - Carbon dots (CDs) have attracted extensive attention over the past decade due to
      their excellent advantages. However, few attempts have been reported for
      realizing the long-wavelength emission, especially for obtaining efficient solid
      state red emission with high photoluminescence quantum yield (QY). Herein, we
      developed highly red light emitting CDs by the step-by-step surface modifications
      of the nitrogen-doped CDs. By introducing hexadecyltrimethyl ammonium bromide to
      modulate a red CD aqueous solution, the photoluminescence QY increases from 23.2%
      to 43.6%. Furthermore, we dispersed CDs in a PVP matrix for a solid-state film,
      where the solid-state quenching was effectively suppressed, and high QY (41.3%)
      of red light emission was achieved. Taking advantage of the as-prepared red light
      emitting CDs combining with the reported high quantum yield blue and green light
      emitting CDs, we realized UV-pumped WLEDs with tunable correlated color
      temperature from 7879 to 2961 K. Moreover, a high color rendering index (CRI) of
      93 for WLEDs was realized, which is superior than the best records for the
      semiconductor quantum dot based WLEDs. Finally, the red light emitting CDs were
      demonstrated to have promising application as a red color converter in
      traditional YAG-based WLEDs to improve their CCT and CRI.

PMID- 29446776
TI  - Steric control and the mechanism of benzaldehyde oxidation by polypyridyl
      oxoiron(iv) complexes: aromatic versus benzylic hydroxylation of aromatic
      aldehydes.
AB  - The present study describes the first example of the hydroxylation of
      benzaldehydes by synthetic nonheme oxoiron(iv) complexes, where the reactivity,
      chemoselectivity, and mechanism were strongly influenced by the ligand
      environment of the iron center.

PMID- 29446777
TI  - Very high commutation quality factor and dielectric tunability in nanocomposite
      SrTiO3 thin films with Tc enhanced to >300  degrees C.
AB  - We report on nanoengineered SrTiO3-Sm2O3 nanocomposite thin films with the
      highest reported values of commutation quality factor (CQF or K-factor) of >2800
      in SrTiO3 at room temperature. The films also had a large tunability of
      dielectric constant (49%), low tangent loss (tan delta = 0.01) and a Curie
      temperature for SrTiO3 > 300  degrees C, making them very attractive for tunable
      RF applications. The enhanced properties originate from the unique nanostructure
      in the films, with <20 nm diameter strain-controlling Sm2O3 nanocolumns embedded
      in a SrTiO3 matrix. Very large out-of-plane strains (up to 2.6%) and high
      tetragonality (c/a) (up to 1.013) were induced in the SrTiO3. The K-factor was
      further enhanced by adding 1 at% Sc3+ (acceptor) dopant in SrTiO3 to a value of
      3300 with the tangent loss being <=0.01 up to 1000 kV cm-1.

PMID- 29446778
TI  - Ir(iii) complex-based phosphorescence and electrochemiluminescence
      chemodosimetric probes for Hg(ii) ions with high selectivity and sensitivity.
AB  - Mercury, one of the most prevalent toxic metal elements, poses severe risks to
      human health and the environment. Several molecular probes have been developed
      for colorimetric and fluorometric detection of Hg(ii) ions. Nevertheless,
      development of a rapid, selective, and sensitive probe for Hg(ii) ions remains
      important. Herein, we report three Ir(iii) complex-based phosphorescence and
      electrochemiluminescence chemodosimeters for the selective detection of Hg(ii)
      ions. The acetylacetonate ancillary ligand of probe 1 reacts selectively with the
      Hg(ii) ion, inducing phosphorescence enhancement with a concomitant blue-shift.
      Meanwhile, the Hg(ii) ion selectively quenches the phosphorescence of probe 2.
      Probes 1 and 2 showed low detection limits (LOD) of 73 and 160 nM, respectively.
      In addition, the Hg(ii) ion level was successfully monitored by the
      electrochemiluminescence decrement of probe 9 with a good linear correlation
      between 0 and 40 MUM, with a detection limit of 170 pM.

PMID- 29446784
TI  - Clinical comparison between an opaque and a clear pit and fissures sealants: a 12
      month split-mouth, randomized controlled study.
AB  - TRIAL DESIGN: We design a clinical splith-mouth, randomized controlled study, in
      which the retention of an opaque and clear pit and fissures sealants were
      evaluated and their effectiveness compared at 6 and 12 months of follow up. A
      secondary aim was to evaluate the possibility of using a fluorescence based intra
      oral camera through the clear sealant to monitor enamel demineralization.
      METHODS: Consecutive young adolescents with at least two molars with code 0, 1, 2
      caries evidenced following the International Caries Detection and Assessment
      System (ICDAS II) were enrolled. A split-mouth randomized allocation was carried
      out. One skilled operator applied the sealant under 3.5 X magnification. A second
      operator evaluated clinical retention and performed the intra-oral camera
      assessments at 6 and 12 months follow up. RESULTS: A total of 42 patients, (20
      males and 22 females, mean age 14.25) with 176 dental lesions were enrolled. Nine
      patients dropped out accounting for 26 teeth lost during follow up. Overall, a
      total of 150 sealed teeth were evaluated in the study. In 77 cases the clear
      sealant was used, while in 73 the opaque sealant was utilized. The opaque sealant
      rated 100% complete retention at 6 months, and 97.3% at 12 months, while the
      clear selant 91.8% and 85.9% respectively. Demineralization under clear selant
      was registered when sealant partial detachment occurred. CONCLUSIONS: The overall
      retention rate of an opaque sealant was higher than that of a clear sealant after
      12 months of follow-up. This difference may partly be due to difficulty in
      clinical detection of clear sealants during follow-up. Fluorescence based intra
      oral camera seems useful to monitor enamel demineralization in clear sealant.

PMID- 29446785
TI  - Effects of salso-bromo-iodine thermal water in children suffering from otitis
      media with effusion: a randomized controlled pilot study.
AB  - BACKGROUND: Otitis media with effusion (OME) is an ear disorder defined by the
      presence of fluid in the middle ear without signs or symptoms of acute infection.
      The aim of this randomised and controlled pilot study was to evaluate whether the
      treatment with a watery salsobromo- iodine solution, administered by nasal
      douche, could induce ear healing better than isotonic saline in children with
      OME. METHODS: The study was randomized, single-blind, and controlled. Study group
      (40 children) was treated with salso-bromo-iodine thermal water solution and
      Control group (40 children) was treated with isotonic saline; both compounds were
      administered by nasal nebulization with Rinowash nasal douche twice/day for 10
      days a month for 3 consecutive months. Tympanogram and audiometry were performed
      at baseline and after treatment. RESULTS: Salso-bromo-iodine therapy shows better
      and statistically significant trend after treatment when compared to control
      group both for tympanogram results with greater improvement (represented by type
      C tympanogram; p = 0.031) and healing (represented by type A tympanogram; p <
      0.001) and audiometric results, with higher presence of patients with normal
      hearing (p = 0.029) and lower among patients with moderate hypoacusis (p =
      0.014). CONCLUSIONS: The current randomized-controlled pilot study demonstrated
      that watery salso-bromo-iodine solution was effective in the treatment of
      children with OME.

PMID- 29446786
TI  - The synergistic effect between Positivity, socio-demographic factors and smoking
      cessation: results of a cohort study.
AB  - OBJECTIVE: To examine the extent to which a effect does exist between Positivity
      (POS), smoking and socio-demographic factors in determining quitting smoking in
      subjects participating in a Group Counselling Program (GCP) for smoking
      cessation. METHODS: 481 subjects were contacted through a telephone call. A
      logistic regression analysis was carried out. Possible interaction between
      sociodemographic variables and POS level was tested using the Synergism Index
      (SI). RESULTS: For individuals with a POS level over or equal to 3.4 the odds of
      being smoker was significantly higher among females (OR = 1.55), who smoked at
      home (OR = 2.16) and lower if there had children at home (OR = 0.53). For
      individuals with a POS level under 3.4, the only significant variable associated
      with smoking was beinga female (OR = 2.58). As far concerns the synergistic
      effect between the variables considered does exist between POS levels and having
      children at home (SI=1.13) and female gender (SI = 2.8). CONCLUSIONS: The
      synergistic effect between POS and sociodemographic factors adds evidence on the
      use of POS as possible determinants of individual happiness.

PMID- 29446787
TI  - The treatment of femoral fractures in children with cerebral palsy.
AB  - OBJECTIVE: The purpose of this study is to retrospectively evaluate a group of
      children affected by cerebral palsy with a recent femoral fracture, and to
      analyse the results and complications in relation to the treatment used.
      MATERIALS AND METHODS: The analysis was performed on 36 children (21 M, 15 F, 8
      14 years old) with cerebral palsy (7 diplegia, 28 tetraparesis, 1 hemiplegia)
      with a metaphyseal or a diaphyseal femoral fracture. The patients were subdivided
      into two groups according to their Gross Motor Function Classification System
      (GMFCS) level: level 2-3 (9 patients) and level 4-5 (27 patients), evaluating the
      presence of complications and malunions for each group at the end of each follow
      up. RESULTS: The fractures were displaced in 24 patients and nondisplaced in 12
      patients. In 26 cases the treatment involved a closed reduction and
      immobilisation in a long leg hip spica cast for 7 weeks, while in 10 cases the
      treatment involved an open reduction-internal fixation (ORIF) followed by a 3
      week period in a plaster coated fracture bandage. CONCLUSIONS: Taking into
      consideration the maximum possible recovery of function, an ORIF is preferable to
      prevent malunion, particularly in distal metaphysis and distal shaft fractures.
      In the GMFCS level 2-3 patients, surgery has allowed to recover, or at least
      maintain, the pre-fracture functional level, while in patients with GMFCS level 4
      5, it has allowed to reduce the immobilisation times and prevent the development
      of decubitus lesions.

PMID- 29446788
TI  - The potential role of herbal products in the treatment of Parkinson's disease.
AB  - Parkinson's disease (PD) is a multifactorial disorder of the nervous system in
      which there is a progressive loss of dopaminergic neurons. There is a disturbance
      in the movement in PD and these include resting tremors, rigidity, bradykinesia
      or akinesia, disturbance, posture and freezing (motor block). The substantia
      nigra and other parts of the brain are commonly affected. The disorder could be
      related to oxidative stress and there is an important role of reactive oxygen
      species (ROS). A number of herbal products contain active components which are
      known to possess antioxidant action. Hence, the potential role of herbal products
      in treating PD cannot be undermined. In the present narrative review, the main
      aim is to discuss the pathogenesis of PD, define the role of different potential
      herbal extracts on its pathogenesis which may form the basis of treatment. We
      also discuss in detail the active chemical compounds present each herb which are
      effective in the treatment of PD. These herbs include Baicalei, Erythrina
      velutin, Resveratrol, Peganum Harmal, Curcuma longa (Zingiberaceae), Carthamus
      tinctorius L. (Safflower), Pueraria lobate, Juglandis Semen (Walnut), Tianma
      Gouteng Yin (TGY), Lycium barbarum L fruit, Mucuna pruriens (Velvet bean),
      Chunghyuldan (CHD), Paeoniae Alba Radix. The present review may be beneficial for
      designing future drugs for effective treatment of PD.

PMID- 29446789
TI  - Medical advancements: emergency contraception (EC). Medico-legal implications of
      EC on adolescents.
AB  - The article's main focus is documenting what the best options are in order to
      make sure that minors are allowed to play a key role in the management of issues
      arising from the use of emergency contraception. In that regard, there is a lack
      of clean-cut legislative measures and, although there are several legal and
      ethical norms designed to get parents or legal guardians involved in such
      decisions, there seems to be an increasingly widespread tendency to give weight
      to the minor's will, thus acknowledging her decision-making capacity. Lastly, the
      paper's authors undertake a thorough examination as to what the duties of doctors
      are, and the measures that need to be put in place in order to safeguard the
      minor patients' conditions. They arrive at the conclusion that emergency
      contraception is suitable for minors even in absence of the stated consent from
      their parents or guardians, but it is of utmost importance to implement adequate
      measures aimed at the provision of proper care, prevention and education.

PMID- 29446790
TI  - Assisted heterologous fertilization and the right of donorconceived children to
      know their biological origins.
AB  - The paper's main goal is to elaborate on the ethical issues that heterologous
      fertilization has raised as to the right of children thus conceived to find out
      about their origins. Such a quandary revolves around the following questions: Is
      it the right thing to inform the child as to the way he or she was conceived? If
      it is, does said child have a right to know his or her biological parent and
      genetic background too? Authors point out that there is no unanimity of judgment
      among experts, and it is worth weighing all reasons in favor and against
      acknowledging the children's right to full knowledge of their biological parents'
      data. Laws regulating the issue in different countries vary substantially as
      well. Therefore, the authors advocate for shared legislation, centered on the
      children's best interest.

PMID- 29446791
TI  - A Practical Look at Diagnosis and Management of Headaches, Anemia, and Our Role
      as Pediatric Providers.

PMID- 29446792
TI  - Anemia in Childhood.
AB  - Anemia is a pervasive problem in pediatrics and evaluating for it is considered
      part of standard care for all pediatric patients. If left untreated, it can cause
      significant problems for children and many of the detriments can be long lasting.
      Although iron deficiency anemia is the most common form of pediatric anemia, it
      is important to keep the broad differential in mind for those in whom the history
      suggests an alternate diagnosis or who do not respond to standard treatment with
      iron supplementation. This article gives a basic overview of anemia in children
      with a focus on iron deficiency. [Pediatr Ann. 2018;47(2):e42-e47.].

PMID- 29446793
TI  - Headaches in Children.

PMID- 29446794
TI  - Migraine Variants in Children.
AB  - Migraine in children can manifest in ways that are markedly different from adult
      migraines. In children, migraine variants are often unaccompanied by headache and
      include conditions such as cyclic vomiting and abdominal migraine. Children who
      experience these conditions are often thought to have a disorder of the
      gastrointestinal tract, and when evaluation is unremarkable they may be diagnosed
      as having a conversion reaction. Complicated migraines, on the other hand, are
      often accompanied by focal neurological symptoms such as ataxia, hemiparesis, or
      altered level of consciousness that evoke great consternation in the examining
      clinician. Certain episodic syndromes that may hold interest to pediatricians are
      also discussed in this article, mostly to emphasize the ambiguity that still
      surrounds these disorders, such as migraine triggered by trauma. The cardinal
      rule that most of these disorders are diagnoses of exclusion and can only be
      confirmed after extensive evaluation, either by the pediatrician or pediatric
      neurologist, is emphasized. [Pediatr Ann. 2018;47(2):e50-e54.].

PMID- 29446795
TI  - Management of Pediatric Migraine: Current Therapies.
AB  - Migraine is one of the most common neurologic conditions in pediatrics. It can be
      a significant stressor, causing absences from school and interruption of parents'
      work and family schedules. The mainstay of treatment remains educating patients
      about healthy lifestyle practices and the influences of sleep, stressors, and
      hydration on triggering migraine attacks. Psychological therapies such as
      biofeedback or cognitive-behavioral therapy may be beneficial in some patients,
      especially those with prominent psychological comorbidities. New advances in the
      pathophysiology of migraine and additional pediatric approval of abortive therapy
      with triptans have led to significant advances in the management of migraine in
      children. Some challenges to preventive therapy were recently noted with the
      negative results obtained in the Childhood and Adolescent Migraine Prevention
      Study, which compared prescription drugs to placebo. Inherent differences between
      adult and pediatric headaches, with shorter duration of pediatric migraine and
      prominent placebo effect, present recurring challenges for clinicians. [Pediatr
      Ann. 2018;47(2):e55-e60.].

PMID- 29446796
TI  - Posttraumatic Headache.
AB  - After sustaining a concussion or mild traumatic brain injury, headaches are one
      of the most common complaints. The pathophysiologic changes that occur in the
      setting of injury likely contribute to or cause posttraumatic headaches.
      Posttraumatic headaches often present as migraine or tension-type headaches.
      Unlike pain from other types of injuries, headaches following mild traumatic
      brain injury are more likely to persist. Preexisting conditions such as migraine
      and mood disorders may influence posttraumatic headache and complicate
      management. Patients are at high risk to overuse abortive medications and develop
      medication overuse headache. Headache hygiene and early education are essential
      for effective management. Abortive medications include nonsteroidal anti
      inflammatory drugs and triptans. Preventive medications include tricyclic
      antidepressants and antiepileptics. Patients who fail outpatient therapies may
      benefit from referral for intravenous medications in the emergency department.
      Patients with persistent posttraumatic headache may benefit from multimodal
      treatments including physical rehabilitation and pain-focused cognitive
      behavioral therapies. [Pediatr Ann. 2018;47(2):e61-e68.].

PMID- 29446797
TI  - Uncommon Pediatric Primary Headache Disorders.
AB  - Migraine and tension-type headaches are common primary headache disorders
      encountered among children and adolescents presenting to a pediatric clinic. At
      times, children present with a headache with unusual or peculiar features that
      can be alarming and perplexing. These can be in the form of a brief stabbing
      headache with lacrimation in one eye or a continuous headache locked to one side
      of the head or face. These headache syndromes tend to be more common among adults
      but, on occasion, are known to occur or have their onset during childhood. This
      review outlines some of the uncommon primary headache disorders in children and
      adolescents that may be encountered in a pediatric clinic. Knowledge of these
      interesting conditions may avert the need for immediate neurological consultation
      and prevent delays in initiating specific therapy. [Pediatr Ann. 2018;47(2):e69
      e73.].

PMID- 29446798
TI  - Life-Threatening Headaches in Children: Clinical Approach and Therapeutic
      Options.
AB  - Life-threatening headaches in children can present in an apoplectic manner that
      garners immediate medical attention, or in an insidious, more dangerous form that
      may go unnoticed for a relatively long period of time. The recognition of certain
      clinical characteristics that accompany the headache should prompt recognition
      and referral to an institution equipped with neuroimaging facilities, pediatric
      neurosurgeons, and neurologists. Thunderclap headaches, which reach a peak within
      a very short period of time, may be the presenting feature of conditions such as
      arterial dissection, venous sinus thrombosis, and reversible cerebral
      vasoconstriction syndrome, which can be addressed by specific pharmacological
      options instituted in an intensive care setting. On the other hand, subacute to
      chronic headaches that are accompanied by focal neurological signs, such as
      abducens nerve palsy, restriction of upward gaze, or papilledema, may be
      indicative of the need for urgent imaging and neurosurgical referral. [Pediatr
      Ann. 2018;47(2):e74-e80.].

PMID- 29446799
TI  - Autoimmune Hepatitis in Children.
AB  - Autoimmune hepatitis (AIH) is an immune-mediated, inflammatory liver disease.
      Clinical presentation of AIH in children is highly variable. It can present
      acutely, chronically, or silently. There are two main types of AIH-type 1 and
      type 2, which are differentiated and defined by the presence of specific
      autoantibodies. AIH eventually progresses to cirrhosis when left untreated, and
      occasionally even with treatment. AIH must be suspected and excluded in all
      children presenting with signs of acute, prolonged, or severe liver disease. The
      diagnosis of AIH is made by a combination of clinical manifestations, laboratory
      evaluation, histopathology, and the exclusion of other more common liver
      diseases. The best outcome for AIH is dependent on early diagnosis as well as
      early initiation of immunosuppressant therapy. [Pediatr Ann. 2018;47(2):e81
      e86.].

PMID- 29446800
TI  - Biology of Vibrio cholera. Editorial overview.
AB  - In this monographic issue, we have the pleasure to present contributions from six
      of the leading laboratories at the forefront of Vibrio cholerae genetics, ecology
      and evolution, together with a brief tribute by Diego Romero to Doctor Jaime
      Ferran y Clua, a pioneering Spanish bacteriologist who developed the first
      vaccine against this pathogen. V. cholerae is a free-living aquatic bacterium
      that interacts with and infects a variety of organisms. In humans it causes
      cholera, the deadly diarrhoea that was responsible for millions of deaths during
      seven pandemics since 1817, and still thousands every year. The Boucher lab
      presents a study of the ecology, evolution and dispersal of pandemic V. cholerae
      biotypes in relation to environmental reservoirs. They show how both species
      specific and lineage-specific genetic determinants play a role in the ability of
      V. cholerae strains to cause pandemics, having evolved gradually over centuries.
      One of the key aspects that makes a particularly successful pathogen is its
      genomic plasticity. The V. cholerae genome contains a superintegron (SI) that is
      involved in development and dissemination of antibiotic resistance genes among
      diverse bacterial species, permitting population expansion in challenging
      conditions. Escudero and Mazel review the SI as a true hotspot of V. cholerae's
      genomic diversity and low-cost memory of adaptive functions in its complex
      lifestyle and ecology. Another remarkable aspect of V. cholerae 's genetics is
      the presence of two chromosomes. Segregation and division in multi-chromosomal
      becteria is relatively complex, and V. cholerae remains the paradigm. Espinosa
      and colleagues review the cell cycle of V. cholerae , comparing and contrasting
      with that of E. coli . In addition to genome plasticity, V. cholerae uses a
      variety of attack/defence strategies to compete and thrive in different niches,
      through interaction with bacteriophages, bacteria and eukaryotes. The role of
      phages in the life cycle of V. cholerae has been increasingly recognized and
      investigated over the past decade. Andrew Camilli and colleagues take us through
      the exciting evolutionary arms race between V. cholerae and virulent
      bacteriophages, based both on mechanisms of phage resistance in the bacterium and
      a unique phage-encoded CRISPR-Cas system used to counteract this resistance.
      Finally, the authors discuss the impact of these predator-prey dynamics in the
      context of infection, and their use as a strategy to limit cholera transmission
      within a community. In regards to its ability to coexist with other microbes, V.
      cholerae can produce effectors that are either released to the extracellular
      media, or delivered via intimate cell-to-cell contact such as those injected via
      the type VI secretion system (T6SS). The Pukatzki lab reviews the versatility of
      the T6SS to produce different combinations of such effectors, which establishes
      the strains of V. cholerae that can co-exist in the environment. After killing a
      cell, its DNA is released and incorporated by natural competence into other
      living cells, thereby being a potential source of diversification for V.
      cholerae's T6SS effectors. Finally, I revisisit the discovery of non-canonical D
      amino acids, recently identified effectors secreted by V. cholerae which have
      increasingly been shown to be important in enhancing the ability of the bacterium
      to colonize and persist in a particular niche. I focus on recent observations
      that suggest different D-amino acids influence distinct cellular processes in
      bacteria, and dis cuss their role in modulating environmental bacterial
      biodiversity.

PMID- 29446801
TI  - Emergence, ecology and dispersal of the pandemic generating Vibrio cholerae
      lineage.
AB  - Although cholera is an ancient disease that first arose at least half a
      millennium ago, it remains a major health threat globally. Its pandemic form is
      caused by strains from a single lineage of the bacterium Vibrio cholerae. The
      ancestor of this lineage harbored several distinctive characteristics, the most
      notable being the O1 antigen polysaccharide. This lineage generated two biotypes,
      first Classical, responsible for six pandemics, and later El Tor, responsible for
      the seventh and ongoing pandemic. Just as El Tor replaced Classical as the main
      cause of outbreaks in the last fifty years, several variants of El Tor have
      evolved and displaced their predecessors worldwide. Understanding the ecology,
      evolution and dispersal of pandemic V. cholerae is central to studying this
      complex disease with environmental reservoirs. Here, we present recent
      advancements of our knowledge on the emergence and spread of the pandemic
      generating lineage of V. cholerae in the light of established eco-evolutionary
      observations. Specific ecological interactions shape seasonal cholera, playing a
      role in the abundance and distribution of its causative agent. Both species
      specific and lineage-specific genetic determinants play a role in the ability of
      V. cholerae strains to cause pandemics with seasonal outbreaks, having evolved
      gradually over centuries. On the basis of the current understanding, we outline
      future threats and changes in biogeographical and genomic-based investigation
      strategies to combat this global problem.

PMID- 29446802
TI  - Mechanisms of the evolutionary arms race between Vibrio cholerae and Vibriophage
      clinical isolates.
AB  - This review highlights recent findings on the evolutionary arms race between the
      causative agent of cholera Vibrio cholerae and virulent bacteriophages (phages)
      ICP1, ICP2, and ICP3 isolated from cholera patient stool samples. We discuss
      mechanisms of phage resistance such as a unique phage-inhibitory chromosomal
      island and mutations that affect phage receptor expression. We also discuss the
      molecular characterization of ICP1 and its unique CRISPR-Cas system, which it
      uses to combat the phage-inhibitory chromosomal island. The role of phages in the
      life cycle of V. cholerae has been increasingly recognized and investigated in
      the past decade. This article will review hypotheses as to how the predator-prey
      relationship may have an impact on infections within individuals and on the self
      limiting nature of cholera epidemics. In addition, we put forth a strategy of
      using phages as an intervention to reduce household transmission of cholera
      within a community.

PMID- 29446803
TI  - Coordination between replication, segregation and cell division in multi
      chromosomal bacteria: lessons from Vibrio cholerae.
AB  - Bacteria display a highly flexible cell cycle in which cell division can be
      temporally disconnected from the replication/segregation cycle of their genome.
      The accuracy of genetic transmission is enforced by restricting the assembly of
      the cell division apparatus to the low DNA-density zones that develop between the
      regularly spaced nucleoids originating from the concurrent replication and
      segregation of genomic DNA. In most bacteria, the process is simplified because
      the genome is encoded on a single chromosome. This is notably the case in
      Escherichia coli, the most well studied bacterial model organism. However, ~10%
      of bacteria have domesticated horizontally acquired mega-plasmids into extra
      numerous chromosomes. Most of our current knowledge on the cell cycle regulation
      of multi-chromosomal species derives from the study of replication, segregation
      and cell division in Vibrio cholerae, the agent of the deadly epidemic human
      diarrheal disease cholera. A nicety of this model is that it is closely related
      to E. coli in the phylogenetic tree of bacteria. Here, we review recent findings
      on the V. cholerae cell cycle in the context of what was previously known on the
      E. coli cell cycle.

PMID- 29446804
TI  - T6SS intraspecific competition orchestrates Vibrio cholerae genotypic diversity.
AB  - Vibrio cholerae is a diverse species that inhabits a wide range of environments
      from copepods in brackish water to the intestines of humans. In order to remain
      competitive, V. cholerae uses the versatile type-VI secretion system (T6SS) to
      secrete anti-prokaryotic and anti-eukaryotic effectors. In addition to competing
      with other bacterial species, V. cholerae strains also compete with one another.
      Some strains are able to coexist, and are referred to as belonging to the same
      compatibility group. Challenged by diverse competitors in various environments,
      different V. choleare strains secrete different combination of effectors -
      presumably to best suit their niche. Interestingly, all pandemic V. cholerae
      strains encode the same three effectors. In addition to the diversity displayed
      in the encoded effectors, the regulation of V. cholerae also differs between
      strains. Two main layers of regulation appear to exist. One strategy connects
      T6SS activity with behavior that is suited to fighting eukaryotic cells, while
      the other is linked with natural competence - the ability of the bacterium to
      acquire and incorporate extracellular DNA. This relationship between bacterial
      killing and natural competence is potentially a source of diversification for V.
      cholerae as it has been shown to incorporate the DNA of cells recently killed
      through T6SS activity. It is through this process that we hypothesize the
      transfer of virulence factors, including T6SS effector modules, to happen.
      Switching of T6SS effectors has the potential to change the range of competitors
      V. cholerae can kill and to newly define which strains V. cholerae can co-exist
      with, two important parameters for survival in diverse environments.

PMID- 29446805
TI  - Genomic Plasticity of Vibrio cholerae.
AB  - Vibrio cholerae is one of the deadliest pathogens in the history of humankind. It
      is the causative agent of cholera, a disease characterized by a profuse and
      watery diarrhoea that still today causes 95.000 deaths worldwide every year. V.
      cholerae is a free living marine organism that interacts with and infects a
      variety of organisms, from amoeba to humans, including insects and crustaceans.
      The complexity of the lifestyle and ecology of V. cholerae suggests a high
      genetic and phenotypic plasticity. In this review, we will focus on two peculiar
      genomic features that enhance genetic plasticity in this bacterium: the division
      of its genome in two different chromosomes and the presence of the superintegron,
      a gene capture device that acts as a large, low-cost memory of adaptive
      functions, allowing V. cholerae to adapt rapidly.

PMID- 29446806
TI  - Divergent functional roles of D-amino acids secreted by Vibrio cholerae.
AB  - The L-forms of amino acids are used in all kingdoms of life to synthesize
      proteins. However, the bacterium Vibriocholerae, the causative agent of cholera,
      produces D-amino acids which are released to the environment at millimolar
      concentrations. We baptized these D-amino acids as non-canonical D-amino acids
      (NCDAAs) since they are different from those (i.e. D-alanine and D-glutamate)
      normally present in the bacterial cell wall. In V. cholerae, production of NCDAAs
      relies on the BsrV enzyme, a periplasmic broad spectrum racemase. BsrV
      multispecific activity, produces of a wide range of distinct D-amino acids. Using
      a combination of genetics and molecular physiology approaches we have
      demonstrated that NCDAAs target different cellular processes which may function
      as part of a cooperative strategy in vibrio communities to protect non-producing
      members from competing bacteria. Because NCDAA production is widespread in
      bacteria, we anticipate that NCDAAs are relevant modulators of microbial
      subpopulations in diverse ecosystems.

PMID- 29446807
TI  - Peritoneal dialysis: Experience of the Department of Pediatrics of the Hospital
      Charles Nicolle of Tunis.

PMID- 29446808
TI  - Private public partnership: a solution for the development of health system in
      Tunisia.
AB  - In a context of economic difficulties, the Tunisian government is required to
      find solutions to meet the expectations of the population. Health sector is one
      of the critical areas requiring radical reform. The objective of this paper is to
      find the place of public private partnership project in the harmonious
      development of both public and private sectors in Tunisia. Indeed, the Tunisian
      health system consists of two main sectors: the public sector, and the private
      sector, booming since the 90s. Tunisian infrastructure and staff resources
      distribution is characterised by a very significant regional disparity, to the
      detriment of the interior regions, which is more pronounced in the private
      sector. This area, considered innovative and responsive, captures the local
      wealthy clientele, and the foreign highly specialized care seekers. It wins over
      the best healthcare providers, inspite of some reported claims against pricing
      abuses leading to user's lack of confidence. As for the public sector under
      funded, handicapped by red tape and some forms of lack of transparency and
      lobbying, it can not cope with the influx of customers of poor and middle
      classes. The relationship between the two sectors misses often. The current
      challenge in the Tunisian health sector is how can public and private sectors
      combine and harmonize their efforts to achieve common interest objectives. The
      public-private partnership, is a process helping the state to involve private
      investors in the realization of public interest projects and develop long term
      contracts. So, the two sectors will share resources and technical expertise and
      will access to further advantages. However, it is essential to establish clear
      and effective legal and institutional frameworks governing private participation
      in the public sector.

PMID- 29446809
TI  - Cost of common low back pain and lumbar radiculopathy in rheumatologic
      consultation in Lome.
AB  - BACKGROUND: The cost of low back pain was the subject of few studies in black
      Africa. AIM: To assess the cost of common low back pain and lumbar radiculopathy
      in Lome. METHODS: A six months study was realised in the rheumatologic department
      of CHU Sylvanus Olympio. 103 consecutive patients suffering from a common low
      back pain or lumbar radiculopathy were included. To assess direct, indirect and
      non-financial costs they were questioned about their expense during the year.
      RESULTS: Financial cost of common low back pain and lumbar radiculopathy amounted
      to 107.2 $ US (extremes: 5.8 and 726.1 $ US). This amount, quadruple of
      guaranteed minimum wage, felled under two headings: direct cost (56.3 $ US; 53%
      of total sum), indirect cost (50.3 $ US; 47% of total sum). Non-financial cost
      were: disruption in daily activities (94%), impact in emotional and sexual life
      (59%), impact on the family's budget (69%), abandon of family's projects (58%) or
      of leisure (42%). CONCLUSION: In black Africa top priority is given to the fight
      against infectious diseases those cause an important mortality. But common low
      back pain and lumbar radiculopathy, those have social and economic impact, should
      be given more attention.

PMID- 29446810
TI  - Postoperative Endophtalmities: therapeuthic results and Early vitrectomy.
AB  - BACKGROUND: Postoperative endophthalmitis is a public health issue due to its bad
      prognosis; its treatment is both surgical and medical. Classically, surgical
      treatment was done if visual acuity is limited to light perception only. AIM: To
      evaluate therapeutic results Of postoperative endophtalmitieS and to Compare
      therapeutics almost used intravitreal injection of antibiotics versus early
      vitrectomy. METHODS: It's a retrospective comparative study  includIng 120 cases
      of acute postoperative endophthalmitis hospitalized in a referral ophthalmology
      department between July 2007 and June 2013. A comparison was conducted between
      two groups of 24 and 94 patients; the first-line treatment was early vitrectomy
      for the first group and intravitreal antibiotic injection alone for the second
      group. RESULTS: The overall incidence rate was 0.38 %, Streptococcus and
      Staphylococcus Epidermidis where the most common bacterial strain (16 patients
      each). The treatment outcome was very favorable for 11 patients with final visual
      acuity  higher or equal to 2/10, the outcome was intermediate for 43 patients and
      poor for 66 patients because of final visual acuity lower than or equal to 1/20,
      loss of media transparency or anatomical or functional loss of the eye. The
      prognostic factors statistically correlated to treatment outcome where intense
      initial inflammation (p<0.001), high bacterial virulence (p=0.002), bacteria
      culture positive to Streptococcus (p=0.024), a defectuous operative incision (p=
      0.012), age over 80 (p=0.022) and posterior capsule rupture (p=0.013). Early
      vitrectomy group (group1) achieved a higher percentage of good outcome (60% vs
      41.5%,  p=0.098 ). CONCLUSION: Functional result is better in the Vitrectomy
      group than in the antibiotic intravitreal injections group whereas not Statically
      signifiant.

PMID- 29446811
TI  - Nosocomial infections: current situation in a resuscitation-unit.
AB  - BACKGROUND: The nosocomial infection (NI) is defined as an infection that is not
      present or incubating on admission in establishment of care. It can be caused by
      the patient's germs, care personnel or hospital environment. Multidrug resistant
      (MDR) bacteria are particularly common in intensive care units that lead to a
      serious infections and increase morbidity, mortality and cost of care. PURPOSE:
      To identify the epidemiological characteristics of NI, the predisposing factors,
      the antimicrobial sensitivity pattern of isolated bacteria and the impact on
      morbidity and mortality. METHODS: Observational study over the year 2013. All
      infected patients hospitalized for at least 48 hours were included unless
      infection has been documented at admission. The type of sampling and
      bacteriological analyzes were performed based on the infection site according to
      the classification of Coordination Committee for the Fight against Nosocomial
      Infection of 2012. Statistical analysis was performed using the SPSS software 20.
      A p value <0.05 was considered significant. RESULTS: 63 patients were included
      with an average age of 51 years and SAPS II at 38. 95% of included patients were
      ventilated and 100% had a central catheterization. 164 infectious episodes were
      documented. The number of infection episodes per patient was statistically
      correlated with the length of stay. The most common isolated microorganism was
      Acinetobacter baumannii. It remains sensitive to colistin in 87.5% of cases. It
      was noted an emergence of Carbapenemase Producing Enterobacteriaceae (12%). The
      major identified risk factors were: previous organ failure, sepsis and
      catecholamines use (respective OR at 2.72, 2.56 and 2.15). Death was attributed
      to nosocomial infection in 36.6% of cases. CONCLUSION: The incidence of
      nosocomial infections is constantly rising in intensive care units. Pneumonia
      remains the most common infectious site. Contributing factors are an anterior
      organ failure, sepsis and catecholamines use. Approximately, one infected patient
      among three died by nosocomial infection.

PMID- 29446812
TI  - Surgical management of primary crohn's disease. descriptive study about 226
      patients.
AB  - BACKGROUND: The surgery is required in more than 80% of patients with Crohn's
      disease (CD). Studies before confirm the specific genetic variation of CD in the
      Tunisian population compared with the others ethnic groups. AIM: This article
      aims to study the epidemiological, anatomical and therapeutic principles of
      surgical forms of CD in a cohort of Tunisian patients. METHODS: We report a
      retrospective study from January 1998 to September 2010 that studied 226 patients
      originated only from Tunisia (in North Africa), operated on for MC. We had been
      interested in epidemiological, anatomical, clinical, therapeutic, topographic
      progression of the disease, the procedure and the postoperative follow-up.
      RESULTS: The median age was 33 years. The average time between the onset of the
      disease and the surgical procedure was 31 months. The diagnosis of CD was
      established preoperatively in 213 patients (94%). The diagnosis was made
      intraoperatively because of an acute complication in 5 cases (2.2%) and
      postoperatively in 8 cases (3.5%). The most common location was the ileocecal
      junction in 184 cases (81.4%). Achieving the most common was the mixed form
      (stricture and fistula) in 123 cases (54.4%). Operative mortality was 0.04% (n =
      1). Specific morbidity was 8.4% (n = 19). In long term, a surgical recurrence was
      noted in 17 patients (7.5%). In multivariate analysis the independent risk
      factors for surgical recurrence were: smooking (p = 0.012, ORs = 3.57) and post
      operative medical treatment (p = 0.05, ORs = 2.6). CONCLUSIONS: Achieving
      stenosing and fistulizing the ileocecal junction is the most frequent surgical
      form in Crohn's disease. Our series is unique for a lower rate of the
      postoperative recurrence (7.5%).

PMID- 29446813
TI  - Ultrasound monitoring of cervical length in twin Pregnancies.
AB  - BACKGROUND: Preterm delivery is the major cause of adverse outcomes in twin
      pregnancy.  A shortened cervix at 20-24 weeks of amenorrhea is a good predictor
      of preterm birth in asymptomatic patients. However, there are no recommendations
      for serial cervical length measurements for these high risk pregnancies.
      OBJECTIVES: To evaluate the benefits from monthly cervical length monitoring in
      asymptomatic twin pregnancies. METHODS: This was a prospective study. We compared
      two groups of twin pregnancies (groupe 1: patients with a monthly and systematic
      transvaginal ultrasound measurement of the cervical length and groupe2 : patients
      without monitoring of cervical length) in terms of premature labor screening,
      mean gestational age at the diagnosis of preterm labor, time saved by tocolysis
      in case of preterm labor and  mean gestational age at delivery. RESULTS: Ninety
      nine twin pregnancies were included: 35 patients had a systematic, monthly
      cervical length (group1) and 64 women had a traditional prenatal care without
      monitoring of cervical length (group2). A significant relationship between a
      cervical length measured between 22 and 24 weeks of amenorrhea inferior to 30 mm
      and preterm labor with a high specificity (100%) and a high positive predictive
      value (100%). The sensitivity remains average (45%).A significant benefit was
      demonstrated through this systematic ultrasound measurement of cervical length
      for the screening of preterm labor (p=0.018), the time saved by tocolysis
      (p=0.023), as well as the medium gestational age at birth (p=0.046). CONCLUSION:
      Serial cervical length measurements seems to be a significant predictor of early
      preterm birth in asymptomatic twin pregnancies.

PMID- 29446814
TI  - Nerve surgery in obstetric brachial plexus palsy, report of 68 cases.
AB  - BACKGROUND: Obstetric brachial plexus palsy aredue to elongation of the brachial
      plexus during delivery by increasing thedistance between the head and shoulder.
      The majority of paralysis recoverspontaneously, but in some cases, nerve repair
      is necessary. The timing of thisnerve surgery and criteria for its indication are
      topics of discussion in theworld literature.The aim of this study is to
      askdirections and to evaluate the contribution of nerve surgery in improving
      theprognosis of this disease. METHODS: This is a retrospective study thathas
      interested 68 cases of obstetric brachial plexus palsy who needs a nerverepair,
      collected over a 8 year-period (2004 - 2011). We analyzed the musclequotes and
      evaluate the functions of the shoulder, elbow and hand pre and postoperative. A
      minimum 12 months'follow-up was observed. RESULTS: Seventy-eight patients
      werecollected, 33 boys and 35 girls with a 62 days mean age at first
      consultationand a mean birth weight of 4187 grams . The presentation was cephalic
      in 66 cases. Theright side was interested in 66%. Clinically, we reported 50% of
      total brachialplexus palsy and 50% of C5-C6 palsy.The mean age at time of surgery
      was 9 months 10 days. Preoperatively, the shoulder was listed 0 or 1 according to
      Gilbert classification in 70% of cases in the C5-C6 plasy and 90% of the total
      brachial palsy. After a mean follow up of 30 months, the rate was respectively 9%
      and 15%. In 75% of cases of total brachial palsy, the hand was listed 0 according
      to Raimondi scale, while in postoperative, 65% of cases, the hand was listed 2
      and 3 according to Raimondi scale. Nerve rupture was the predominant lesion on
      the C5 and C6 root while fibrosis was predominant on C7, C8 and T1 roots. We
      noted 6 complications including respiratory distress. CONCLUSIONS: The nerve
      repair should not beperformed too early or too late. Too soon, we may operate
      those who can have aspontaneous recovery. Too late, the installation of the
      degeneration of motorendplates and muscle atrophy render unnecessary nerve
      repair. The absence ofbiceps clinical recovery in the 6th month of life and the
      presence of root-wrenching signs represented the absolute surgical indications.
      Its results areencouraging and improve functional outcome.

PMID- 29446815
TI  - Fetoplacental malformations and abnormalities. A retrospective analysis of 398
      cases.
AB  - BACKGROUND: The fetoplacental examination is actually very important and
      sometimes necessary to confirm or correct prenatal diagnosis. AIM: to deduce a
      list of indications of fetoplacental examination and to determine the type and
      frequency of malformations found. METHODS: a retrospective study including 398
      consecutive fetoplacental examinations, including abortions, stillbirths and
      children died perinatally. The cases were referred in the department of pathology
      of the M. Slim Hospital (North Tunis) from 1992 and 2012. RESULTS: The mean
      maternal age was 32,58 years. The average gravidity was 2,65 and the average rate
      was 1,48. Maternal conditions were dominated by preeclampsia. The main indication
      motivating the request for fetoplacental examination was a spontaneous abortion
      in 45,73% of cases. The rate of stillbirths was 15,61% and that of children who
      died in the perinatal period was 13,28%. The sex ratio was 1,4 and the medium
      term was 19,38 SA. 170 fetuses had abnormalities (43,14%). The most frequent
      abnormalities were chromosomal aberrations (27,64%), followed by facial
      abnormalities (25,88%) and central nervous system abnormalities (18,82%). We
      examined 283 placentas, 49% of them contained abnormalities. Ischemic lesions
      were the main placental abnormalities (41%). CONCLUSIONS:   An efficient
      fetopathological examination should be as complete as possible, including
      examination of placenta. Everything must be integrated into a data collection and
      complete clinical information.

PMID- 29446816
TI  - Atrophic tear retinal detachment: clinical characteristics and surgical treatment
      results at long term.
AB  - AIM: to analyse clinical and epidemiological characteristics of atrophic tear
      retinal detachment (ATRD) and evaluate anatomical and functional results.
      METHODS: Retrospective study of 48 cases underwent primary scleral buckling for
      ATRD. Mean follow up was 80,52 months. RESULTS: ATRD represented 7% of all
      reghmatogenous RD. Mean age of patients was 38 years and 7 months. Age was less
      than 40 years in 62,5% of patients. Male predominance was noted. Myopia was noted
      in 67% of cases and 78,12% presented high myopia. Mean delay of consultation was
      7 months ranging from 1 and 60 months. Visual acuity was ranged between light
      perception to 10/10. The AT number in eye varied between1 to 15 (mean 3 tears).
      The seat of AT was preferentially in inferior temporal quadrants than superior
      one. Maculae was detached in 87,5% of cases. All patients underwent scleral
      buckling: longitudinal buckle was performed in 27% of cases, radial sponge was
      put on in 8,3% of eyes and circumferential one was made in 64,5% of cases. Sub
      retinal fluid was punctured in 75% od cases. Retinal reattachment was obtained in
      all cases; after one surgery in 95,83% of cases. Redetachment was observed in 2
      cases: it was linked with unknown AT. Visual acuity was improved in 83,3% of
      cases. It was more than 5/10 in 14,6% of cases. Postoperative hypertonia was
      observed in 18,75% of cases. Choroidal detachment was observed in one case and it
      was resolved spontaneously. Scleral bukle rejection was observed in one case.
      CONCLUSION: ATRD was not associated at posterior vitreous detachment. It was
      observed in young myopic patients. There is a chronic form of retinal detachment
      with many tears. Scleral buckle was the surgical treatment of this type of RD
      with good anatomical prognostic.

PMID- 29446817
TI  - Depression in Tunisian type 2 diabetic patients: prevalence and association to
      glycemic control and to treatment compliance.
AB  - AIM: to study the prevalence of depression in type 2 diabetes and to seek for a
      relationship between glycemic control and treatment adherence. METHODS: This
      cross-sectional study was carried out at the outpatient department of the Tunis
      nutrition institute. A total of 100 diabetic patients followed for Type 2
      diabetes were randomly recruited. We used a structured questionnaire to collect
      patients' socio-demographic, clinical and therapeutic data. The treatment
      adherence was assessed by using MAS, Glycemic control according to blood glucose
      and glycated hemoglobin (HbA1c) levels and depression and anxiety by
      administering a dialectal Arabic validated version of Hospital Anxiety and
      Depression Scale (HAD). Finaly we also used the modules on mood disorders of the
      mini international neuropsychiatric interview (MINI). RESULTS: The prevalence of
      depression in T2DP was 38% according to the HAD scale with severe forms in 18%.
      The anxiety prevalence was 31%. However, 18% of T2DP had anxious-depressive co
      morbidity. According to the MINI, 31% of T2DP had a mood disorder. Dysthymia was
      noted in 14% of cases, an isolated depressive episode in 6%. Depressed T2DP have
      a poor glycemic control than those no depressed. Macro-angiopathy, irregular
      followed-up, poor treatment adherence and unbalanced diet were associated with
      depression. CONCLUSION: The detection of depression related to somatic pathology
      in particular diabetes, seems essential. As a result, depression treatment may
      improve the overall prognosis of the associated somatic diseases.

PMID- 29446818
TI  - Heart involvement in systemic sclerosis.
AB  - INTRODUCTION: Primary and secondary heart involvement in systemic sclerosis are
      important mortality predictors. Aim of this study was to investigate by standard
      echocardiography associated to pulsed-tissue Doppler imaging, six-minute walk
      test (6MWT) and BNP level cardiac manifestation in 30 patients with ScS and to
      establish a strategy to detect and to evaluate this complication. METHODS: This
      was a cross-sectional study conducted over a period of 16 months: a total of 30
      consecutive patients with ScS diagnosed as proposed by the American college of
      Rheumatology and the European League Against Rheumatism 2013 and who were
      hospitalized in Internal Medicine department of Habib Thameur hospital underwent
      cardiac assessment. RESULTS: Twenty-nine patients were female, the mean age of
      diagnosis was 46 years +/- 13,49  [18-71 years]. Echocardiography found left
      ventricular systolic dysfunction (LVSD) on tissue doppler imaging, in 40% of
      cases, it was significantly associated with diffuse ScS (p=0,024), with Scl70
      anti bodies (p=0,043) and interstitial lung disease (p=0,024). However, the left
      ventricular diastolic dysfunction (LVDD) was correlated with a high diastolic
      arterial hypertension (p=0,028), diffuse ScS (0,048), telangiectasia (p=0,029)
      and pulmonary hypertension (p=0,033). Higher systolic pulmonary arterial pressure
      (PAPs) (p=0,029) and higher BNP level (p=0,027) were noted in the group of
      patients with right ventricular systolic dysfunction (RVSD). Patients who had an
      elevated PAPs had: accelerated pulse (p=0,022), a cough (p=0,024), dyspnea III-IV
      (p=0,003), shorter six-minute walk distance (p=0,044), greater Borg score
      (p=0,025) and elevated BNP level (p=0,015). Thus, a positive correlation was
      found between PAPs and BNP (p=0,004, r=+0,53), a negative correlation was noted
      between PAPs and ST (p=0,006, r=-0,49). The ROC curve identified a discriminator
      threshold for ST<11,5cm/s (BNP >=43,5pg/l) and PAPs >35mmHg (BNP >=92pg/l). A
      discriminator value of the 6MWD (>=294m) was recorded for a PAPs >35mmHg. 2000
      3000 salma Conclusion: Left ventricular diastolic impairment was the most
      frequent echographic abnormality in our study. The BNP level and 6MWT are
      sensitive and specific in the detection of an elevation of PAPs.

PMID- 29446819
TI  - Ileoanal J pouch prolapse: a rare complication after restorative coloproctectomy.

PMID- 29446820
TI  - Chronic myeloid leukemia following the treatment of nasopharyngeal carcinoma.

PMID- 29446821
TI  - Malacoplakia mimicking colonic malignancy: A case report.

PMID- 29446822
TI  - Pelvic actinomycosis fistulised to the skin, treated with doxycycline.

PMID- 29446824
TI  - Primary bilateral orbital localization of MALT-type lymphoma in a 77-year-old
      woman.

PMID- 29446823
TI  - A confusing lesion of thyroid papillary carcinoma.

PMID- 29446825
TI  - Phytomedicines (medicines derived from plants) for sickle cell disease.
AB  - BACKGROUND: Sickle cell disease, a common recessively inherited haemoglobin
      disorder, affects people from sub-Saharan Africa, the Middle East, Mediterranean
      basin, Indian subcontinent, Caribbean and South America. It is associated with
      complications and a reduced life expectancy. Phytomedicines (medicine derived
      from plants in their original state) encompass many of the plant remedies from
      traditional healers which the populations most affected would encounter.
      Laboratory research and limited clinical trials have suggested positive effects
      of phytomedicines both in vivo and in vitro. However, there has been little
      systematic appraisal of their benefits. This is an update of a Cochrane Review
      first published in 2004, and updated in 2010, 2013, and 2015. OBJECTIVES: To
      assess the benefits and risks of phytomedicines in people with sickle cell
      disease of all types, of any age, in any setting. SEARCH METHODS: We searched the
      Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials
      Register, the International Standard Randomised Controlled Trial Number Register
      (ISRCTN), the Allied and Complimentary Medicine Database (AMED),
      ClinicalTrials.gov and the World Health Organization (WHO) International Clinical
      Trials Registry Platform (ICTRP).Dates of most recent searches: Cochrane Cystic
      Fibrosis and Genetic Disorders Haemoglobinopathies Trials Register: 10 April
      2017; ISRCTN: 26 July 2017; AMED: 24 August 2017; ClinicalTrials.gov: 02 August
      2017; and the WHO ICTRP: 27 July 2017. SELECTION CRITERIA: Randomised or quasi
      randomised trials with participants of all ages with sickle cell disease, in all
      settings, comparing the administration of phytomedicines, by any mode to placebo
      or conventional treatment, including blood transfusion and hydroxyurea. DATA
      COLLECTION AND ANALYSIS: Both authors independently assessed trial quality and
      extracted data. MAIN RESULTS: Two trials (182 participants) and two
      phytomedicines Niprisan(r) (also known as Nicosan(r)) and Ciklavit(r) were
      included. The Phase IIB (pivotal) trial suggests that Niprisan(r) was effective
      in reducing episodes of severe painful sickle cell disease crisis over a six
      month period (low-quality evidence). It did not affect the risk of severe
      complications or the level of anaemia (low-quality evidence). No serious adverse
      effects were reported. The single trial of Cajanus cajan (Ciklavit(r)) reported a
      possible benefit to individuals with painful crises (low-quality evidence), and a
      possible adverse effect (non-significant) on the level of anaemia (low-quality
      evidence). AUTHORS' CONCLUSIONS: While Niprisan(r) appeared to be safe and
      effective in reducing severe painful crises over a six-month follow-up period,
      further trials are required to assess its role in the management of people with
      sickle cell disease and the results of its multicentre trials are awaited.
      Currently no conclusions can be made regarding the efficacy of Ciklavit(r). Based
      on the published results for Niprisan(r) and in view of the limitations in data
      collection and analysis of both trials, phytomedicines may have a potential
      beneficial effect in reducing painful crises in sickle cell disease. This needs
      to be further validated in future trials. More trials are required on the safety
      and efficacy of phytomedicines used in managing sickle cell disease.

PMID- 29446826
TI  - 1,3,6,7-Tetrahydroxy-8-prenylxanthone ameliorates inflammatory responses
      resulting from the paracrine interaction of adipocytes and macrophages.
AB  - BACKGROUND AND PURPOSE: Chronic inflammation in adipose tissue is critical in the
      onset and development of insulin resistance and type 2 diabetes. Macrophage
      infiltration into adipose tissue and pro-inflammatory polarization play key roles
      in adipose tissue inflammation. The fruit hull of mangosteen (Garcinia
      mangostana) is used in traditional medicine to treat various inflammatory
      diseases. However, its role in regulating adipose tissue inflammation is
      unexplored. This study was designed to identify xanthones from G. mangostana,
      which could ameliorate adipose tissue inflammation. EXPERIMENTAL APPROACH:
      Expressions of inducible NOS, cytokines, chemokines and components of the NF
      kappaB and MAPKs pathways were evaluated using Western blotting,
      immunofluorescence, quantitative real-time PCR or ELISA. The migration of
      macrophages towards adipocytes was tested using Transwell experiments in vitro. A
      murine model of LPS-induced acute inflammation was used to examine effects of
      1,3,6,7-tetrahydroxy-8-prenylxanthone (TPX) on inflammatory responses in adipose
      tissue in vivo. KEY RESULTS: From a series of xanthones isolated from G.
      mangostana, TPX was identified as a potent inhibitor of LPS-induced NO production
      and IL-6 secretion in RAW264.7 macrophages. TPX ameliorated LPS-induced
      inflammatory responses in RAW264.7 macrophages, and TNF-alpha-mediated
      inflammation in 3T3-L1 adipocytes, through inhibiting MAPKs and NF-kappaB
      activation and promoting sirtuin 3 expression. TPX also blocked RAW264.7
      macrophages migration towards 3T3-L1 adipocytes in co-cultures. Furthermore, TPX
      alleviated LPS-induced adipose tissue inflammation in vivo by reducing pro
      inflammatory cytokines and preventing the pro-inflammatory polarization of
      macrophages. CONCLUSIONS AND IMPLICATIONS: Taken together, our results indicate
      that TPX disrupts the inflammatory responses between macrophages and adipocytes,
      and attenuates adipose tissue inflammation.

PMID- 29446827
TI  - Effect of ultrasound dielectric pretreatment on the oxidation resistance of
      vacuum-fried apple chips.
AB  - BACKGROUND: In order to investigate the effect of ultrasound dielectric
      pretreatment on the oxidation resistance of vacuum-fried apple chips, apple
      slices were pretreated at ultrasonic powers of 150, 250 and 400 W for times of
      10, 20 and 30 min before vacuum frying. The quality and oxidation resistance of
      fried apple were evaluated by testing the dielectric properties and comparing the
      moisture content, oil uptake, color, acid value (AV) and peroxide value (PV) of
      apple chips. RESULTS: Ultrasonic treatment significantly changed the dielectric
      properties of apple slices. Moisture and oil contents of apple chips decreased
      with increasing ultrasonic power and time. During storage, the color retention of
      fried apple chips processed by ultrasound was improved. AV and PV values of fried
      apple chips processed by ultrasound were lower, which improved their antioxidant
      properties. CONCLUSION: The results of the present study indicated that
      ultrasound dielectric pretreatment improved not only the quality of vacuum-fried
      apple chips but also their antioxidant properties. (c) 2018 Society of Chemical
      Industry.

PMID- 29446828
TI  - Novel insights on testicular volume and testosterone replacement therapy in
      Klinefelter patients undergoing testicular sperm extraction. A retrospective
      clinical study.
AB  - STUDY QUESTION: To investigate whether sperm recovery is related to clinical
      features, hormone parameters and testosterone replacement therapy (TRT) in
      patients with Klinefelter syndrome (KS). SUMMARY ANSWER: This study provides
      three interesting insights: (i) the probability to retrieve sperm is not related
      to testicular volume; (ii) TRT does not affect sperm retrieval rate (SRR); and
      (iii) reduced levels of LH and FSH represent a negative predictor of sperm
      retrieval in patients with TRT. WHAT IS KNOWN ALREADY: Classical KS shows a
      karyotype with one extra X chromosome in all of somatic cells and clinical
      manifestations characterized by hypergonadotropic hypogonadism and infertility.
      STUDY DESIGN, SIZE AND DURATION: We performed a retrospective cohort study. Data
      from 111 consecutive KS azoospermic patients undergoing testicular sperm
      extraction (TESE) were collected from 2005 to 2016. PARTICIPANTS/MATERIALS,
      SETTING AND METHODS: Data on anthropometric parameters, reproductive hormones and
      testicular volumes were collected. SRR was related to clinical characteristics
      and compared between TRT and untreated patients. MAIN RESULTS AND THE ROLE OF
      CHANCE: A total of 38 patients (34.2%) had successful sperm recovery. The
      comparison of clinical characteristics did not differ between patients with and
      without sperm recovery. Sperm retrieval was successful also in subjects with
      smaller testes. The comparison of SRR in patients with or without TRT was not
      different (33.3% vs 34.6%). In TRT group, LH and FSH levels were significantly
      lower in subjects with no sperm retrieval (P values, respectively, <.05 and
      <.001). LIMITATIONS AND REASONS FOR CAUTION: Well-designed controlled studies are
      necessary to confirm these data aimed to set the best therapeutic approach for
      fertility management in hypogonadal patients with nonmosaic KS. WIDER
      IMPLICATIONS OF THE FINDINGS: Age at TESE, anthropometric measures, testis
      volume, sex hormones levels and semen parameters are not predictive parameters of
      SRR. Among TRT patients, reduced gonadotropin is related to failure in sperm
      retrieval.

PMID- 29446829
TI  - Injection testosterone and adverse cardiovascular events: A case-crossover
      analysis.
AB  - CONTEXT: Exogenous testosterone administration may affect blood clotting,
      polycythaemia, and may increase atherosclerosis, though any association with
      cardiovascular events is unclear. While the literature is inconclusive, some
      studies have suggested testosterone use may increase short-term risk of
      cardiovascular events and stroke, and injection testosterone may convey higher
      risks than other dosage forms. OBJECTIVE: We sought to evaluate the short-term
      cardiovascular risk of receiving injection testosterone. DESIGN: We conducted a
      case-crossover analysis comparing injection testosterone exposure in the 7 days
      prior to an outcome event to referent windows in the past to estimate the acute
      association of cardiovascular outcomes with the receipt of testosterone
      injections. PATIENTS: We identified adult male testosterone users hospitalized
      with myocardial infarction (MI), stroke or a composite of MI, stroke or unstable
      angina in US commercial claims (2000-2013) or Medicare (2007-2010) databases.
      MEASUREMENTS: We identified testosterone use for the patients from pharmacy
      dispensing claims or in-office procedure codes in the insurance billing data.
      RESULTS: We identified 2898 commercially insured men with events and recent
      testosterone use, and 339 from Medicare. Injected testosterone was associated
      with an increased risk of adverse events (composite outcome of myocardial
      infarction, stroke or unstable angina) in the immediate postinjection period for
      the older, Medicare population only: commercial insurance, odds ratios (OR) =
      0.98 (95% confidence intervals [CI]: 0.86-1.12); Medicare, OR = 1.45 (1.07,
      1.98). This association was either greatly attenuated or not present when
      evaluating receipt of any testosterone dosage forms (injection, gel, patch,
      implant): commercial insurance, OR = 1.01 (0.92, 1.11); Medicare, OR = 1.26 (95%
      CI: 0.98-1.63). CONCLUSIONS: Testosterone injections were uniquely associated
      with short-term risk of acute cardio- and cerebrovascular events in older adult
      men following injection receipt.

PMID- 29446830
TI  - Prior ingestion of exogenous ketone monoester attenuates the glycaemic response
      to an oral glucose tolerance test in healthy young individuals.
AB  - KEY POINTS: The recent development of exogenous ketone supplements allows direct
      testing of the metabolic effects of elevated blood ketones without the
      confounding influence of widespread changes experienced with ketogenic diets or
      prolonged fasting. In the present study, we determined the effect of (R)-3
      hydroxybutyl (R)-3-hydroxybutyrate ketone monoester on the glycaemic response and
      insulin sensitivity index during a 2 h oral glucose tolerance test (OGTT) in
      humans. The results obtained show that consuming a ketone monoester supplement 30
      min prior to an OGTT reduced the glycaemic response and markers of insulin
      sensitivity without affecting insulin secretion. The findings of the present
      study provides evidence that ketone supplements could have therapeutic potential
      for future application as a glucose-lowering nutritional supplement. ABSTRACT:
      The main objectives of the present study were: (i) to determine whether acute
      ingestion of ketone monoester (Kme ); (R)-3-hydroxybutyl (R)-3-hydroxybutyrate
      impacts plasma glucose levels during a standardized oral glucose tolerance test
      (OGTT) and (ii) to compare changes in insulin concentrations and estimates of
      insulin sensitivity after acute Kme supplementation. Twenty healthy participants
      (n = 10 males/females) aged between 18 and 35 years took part in a randomized
      cross-over study. After an overnight fast, participants consumed a Kme supplement
      (DeltaG(r); TDeltaS Ltd, UK, Oxford, UK; 0.45 ml kg-1 body weight) or placebo
      (water) 30 min before completing a 75 g OGTT. Blood samples were collected every
      15-30 min over 2.5 h. The participants and study personnel performing the
      laboratory analyses were blinded to the study condition. Kme acutely raised blood
      d-beta-hydroxybutyrate (beta-OHB) to 3.2 +/- 0.6 mm within 30 min with levels
      remaining elevated throughout the entire OGTT. Compared to placebo, Kme
      significantly decreased the glucose area under the curve (AUC; -16%, P = 0.001),
      non-esterified fatty acid AUC (-44%, P < 0.001) and C-peptide incremental AUC (P
      = 0.005), at the same time as improving oral glucose insulin sensitivity index by
      ~11% (P = 0.001). In conclusion, a Kme supplement that acutely increased beta-OHB
      levels up to ~3 mm attenuated the glycaemic response to an OGTT in healthy
      humans. The reduction in glycaemic response did not appear to be driven by an
      increase in insulin secretion, although it was accompanied by improved markers of
      insulin sensitivity. These results suggest that ketone monoester supplements
      could have therapeutic potential in the management and prevention of metabolic
      diseases.

PMID- 29446831
TI  - The importance of key floral bioactive compounds to honey bees for the detection
      and attraction of hybrid vegetable crops and increased seed yield.
AB  - BACKGROUND: Crop breeding programmes generally select for traits for improved
      yield and human consumption preferences. Yet, they often overlook one fundamental
      trait essential for insect-pollinated crops: pollinator attraction. This is even
      more critical for hybrid plants that rely on cross-pollination between the male
      fertile line and the male-sterile line to set seeds. This study investigated the
      role of floral odours for honey bee pollination that could explain the poor seed
      yield in hybrid crops. RESULTS: The key floral bioactive compounds that honey
      bees detect were identified for three vegetable hybrid crops. It was found that
      30% of the variation in bioactive compound quantities was explained by variety.
      Differences in quantities of the bioactive compounds triggered different degrees
      of olfactory response and were also associated with varied appetitive response.
      Correlating the abundance of each bioactive compound with seed yield, it was
      found that aldehydes such as nonanal and decanal can have a strong negative
      influence on seed yield with increasing quantity. CONCLUSION: Using these
      methodologies to identify relevant bioactive compounds associated with honey bee
      pollination, plant breeding programmes should also consider selecting for floral
      traits attractive to honey bees to improve crop pollination for enhanced seed
      yield. (c) 2018 Society of Chemical Industry.

PMID- 29446832
TI  - An assessment of 18 F-FDG PET/CT for thoracic screening and risk stratification
      of pulmonary nodules in multiple endocrine neoplasia type 1.
AB  - CONTEXT: Bronchopulmonary neuroendocrine tumours (bpNETs) and thymic carcinoid
      (ThC) are features of multiple endocrine neoplasia type 1 (MEN 1), and
      surveillance guidelines recommend periodic thoracic imaging. The optimal thoracic
      imaging modality and screening frequency remain uncertain as does the prognosis
      of small lung nodules when identified. OBJECTIVES: To evaluate fluorodeoxyglucose
      positron emission tomography/computed tomography (18 F-FDG PET/CT) for
      identification and prognostic assessment of thoracic lesions in MEN 1. DESIGN:
      Retrospective observational study. SETTING AND PARTICIPANTS: Fifty consecutive
      MEN 1 patients undergoing screening with 18 F-FDG PET/CT at a tertiary referral
      hospital between July 2011 and December 2016. INTERVENTIONS: 18 F-FDG PET/CT.
      OUTCOME MEASURES: Pulmonary and thymic lesion prevalence, size, functional
      characteristics and behaviour. RESULTS: Thirteen patients (26.0%) exhibited
      pulmonary nodules with multiple nodules identified in nine (18.0%). An
      asymptomatic 31 mm FDG-avid ThC was identified in one patient (2%). Of the 13
      patients with pulmonary nodules, four (8.0%) exhibited 13 FDG-avid nodules (mean
      size 10.1 +/- 9.1 mm), and nine (18.0%) demonstrated 26 FDG nonavid nodules (mean
      size 6.9 +/- 5.8 mm). All FDG-avid lesions increased in size vs 11 (42.3%) FDG
      nonavid lesions (P = .0004). For FDG-avid and nonavid nodules, the median
      doubling time was 24.2 months (IQR 11.4-40.7) and 48.6 months (IQR 37.0-72.2),
      respectively. Nodule resection was undertaken in two patients, typical bronchial
      carcinoid diagnosed in one (FDG nonavid) and metastatic renal cell carcinoma in
      the second (FDG avid). CONCLUSION: Thoracic imaging with 18 F-FDG PET/CT
      effectively identifies pulmonary nodules and ThC. FDG-avid pulmonary lesions are
      significantly more likely to progress than nonavid lesions.

PMID- 29446833
TI  - Body fat content, fat distribution and adipocytokine production and their
      correlation with fertility markers in young adult men and women conceived by
      intracytoplasmic sperm injection (ICSI).
AB  - OBJECTIVE: Differences in body fat content during childhood and adolescence have
      been described in offspring conceived by in vitro fertilisation (IVF) and
      intracytoplasmic sperm injection (ICSI). However, data on body fat and its
      distribution as well as on adipocytokine production in young adults conceived by
      ICSI are nonexistent. We investigated if young adult men and women conceived by
      ICSI have a normal body fat patterning and adipocytokine production. DESIGN:
      Cohort study. PATIENTS: One hundred twenty-seven young adults conceived by ICSI
      and 138 peers born after spontaneous conception. MEASUREMENTS: Anthropometric
      parameters (skinfold thickness, hip and waist circumferences), dual X-ray
      absorptiometry (whole body and regional) measurements and adipocytokine levels
      (leptin and adiponectin) were analysed in relation to fertility markers (serum
      anti-Mullerian hormone (AMH) and inhibin B). RESULTS: While at age 18 years, a
      normal body fat distribution and normal leptin and adiponectin production was
      found in both male and female ICSI offspring, young men conceived by ICSI had a
      higher peripheral fat deposition in comparison with spontaneously conceived
      peers. No correlation between AMH and inhibin B with leptin or adiponectin was
      observed. CONCLUSION: While men conceived by ICSI, but not women, had a higher
      peripheral fat deposition, body fat distribution as well as mean levels of
      adipocytokines were not affected by the mode of conception.

PMID- 29446834
TI  - The HDL anti-inflammatory function is impaired in the context of low-normal free
      thyroxine in diabetic and nondiabetic individuals.

PMID- 29446835
TI  - Eudicots from severely phosphorus-impoverished environments preferentially
      allocate phosphorus to their mesophyll.
AB  - Plants allocate nutrients to specific leaf cell types, with commelinoid monocots
      preferentially allocating phosphorus (P) to the mesophyll and calcium (Ca) to the
      epidermis, whereas the opposite is thought to occur in eudicots. However,
      Proteaceae from severely P-impoverished habitats present the same P-allocation
      pattern as monocots. This raises the question of whether preferential P
      allocation to mesophyll cells is a phylogenetically conserved trait, exclusive to
      commelinoid monocots and a few Proteaceae, or a trait that has evolved multiple
      times to allow plants to cope with very low soil P availability. We analysed the
      P-allocation patterns of 16 species from 10 genera, eight families and six orders
      within three major clades of eudicots across different P-impoverished
      environments in Australia and Brazil, using elemental X-ray mapping to
      quantitatively determine leaf cell-specific nutrient concentrations. Many of the
      analysed species showed P-allocation patterns that differed substantially from
      that expected for eudicots. Instead, P-allocation patterns were strongly
      associated with the P availability in the natural habitat of the species,
      suggesting a convergent evolution of P-allocation patterns at the cellular level,
      with P limitation as selective pressure and without a consistent P-allocation
      pattern within eudicots. Here, we show that most eudicots from severely P
      impoverished environments preferentially allocated P to their mesophyll. We
      surmise that this preferential P allocation to photosynthetically active cells
      might contribute to the very high photosynthetic P-use efficiency of species
      adapted to P-impoverished habitats.

PMID- 29446836
TI  - Adverse pregnancy outcomes and future maternal cardiovascular disease.
AB  - Cardiovascular disease (CVD) remains the leading cause of death in women.
      Although traditional risk factors increase later-life CVD, pregnancy-associated
      complications additionally influence future CVD risk in women. Recent guidelines
      for the prevention of CVD in women have added adverse pregnancy outcomes as major
      CVD risk factors. Studies have shown that women with a history of preeclampsia,
      gestational diabetes, preterm delivery, and delivery of a small-for-gestational
      age infant have an increased risk of developing cardiometabolic risk factors and
      subsequent CVD. A history of multiple adverse pregnancy outcomes further
      increases this risk. It has been suggested that these pregnancy complications may
      unmask preexisting elevated CVD risk; however, whether the pathophysiologic
      changes underlying these conditions directly result in long-term cardiovascular
      damage is unclear. The purpose of this review was to highlight the associations
      between adverse pregnancy outcomes and future CVD, and to emphasize the
      importance of considering pregnancy history in assessing a woman's CVD risk.
      Targeted efforts to initiate screening and risk-reduction strategies in women
      with prior history of pregnancy complications, particularly lifestyle
      modification, may help decrease the burden of CVD in women.

PMID- 29446837
TI  - 25-OH-vitamin D, parathyroid hormone, and calcium serum levels in captive common
      marmosets (Callithrix jacchus): Reference values and effect of age, sex, season,
      and closure of long bone epiphyses.
AB  - BACKGROUND: To date, reference values for 25-OH-vitamin D, parathyroid hormone
      (PTH), and calcium in serum of common marmosets (Callithrix jacchus) based on a
      large sample size are not available. METHODS: Serum reference values for these
      parameters were determined and correlated with sex, age, season of sampling, and
      time of long bone epiphyseal closure in captive-housed marmosets. RESULTS AND
      CONCLUSIONS: The 90% reference range for serum 25-OH-vitamin D is 47.40-370.4
      nmol/L, for PTH 2.10-30.51 pmol/L, and for calcium 2.08-2.63 mmol/L. Lower levels
      of vitamin D were measured in fall compared with the other seasons. Levels of PTH
      were higher in males than in females, and calcium levels were lower in younger
      animals compared with older marmosets. No other effects of age, sex, season, or
      timing of growth plate closure were found.

PMID- 29446838
TI  - The Effect of Pyrazolyl Substituents on the Photophysical and Photochemical
      Properties of Pyrazine Derivatives.
AB  - The reaction of 2,5-dibromopyrazine with N-Lithium pyrazolate in a 1:2 ratio
      leads to a mixture of 2-bromo-5-(1H-pyrazol-1-yl)pyrazine (I) and 2,5-di(1H
      pyrazol-1-yl)pyrazine (II). The structures of I and II are highly planar. Two
      absorption bands can be observed for the compounds in the UV-Vis region, having
      epsilon in the order of 104  m-1  cm-1 . TD-DFT computed results support the
      nature of the lower energy absorptions as pipyrazine ->pi*pyrazine transitions,
      including an additional intraligand charge transfer transition for I (pipyrazol 
      >pi*pyrazine ). Upon excitation at 280 or 320 nm, the emission of both compounds
      is almost not affected by solvent polarity or oxygen presence, showing two bands
      for I and one for II in the 350-450 nm region. Emission of II follows a mono
      exponential decay, while I decays following a bi-exponential law, hypothesized
      from pipyrazine ->pi*pyrazine and pipyrazol ->pi*pyrazine transitions.
      Photodegradation of I and II follows a first-order kinetic with constants of 1.18
      * 10-2  min-1 and 0.13 * 10-2  min-1 , respectively. Results suggest that
      photodegradation of I starts with the loose of bromide followed by intermolecular
      pyrazolyl subtraction and ring opening. This path is not available for II, which
      is reflected in its enhanced photostability.

PMID- 29446839
TI  - Siphonaxanthin, a Carotenoid From Green Algae, Inhibits Lipogenesis in
      Hepatocytes via the Suppression of Liver X Receptor alpha Activity.
AB  - Nonalcoholic fatty liver disease (NAFLD) has shown an increasing morbidity in
      recent years. Here, we demonstrated that siphonaxanthin (SPX), a rare marine
      carotenoid, exhibits a strong inhibitory effect on aggravated hepatic lipogenesis
      in vitro and would be a promising candidate in the prevention and alleviation of
      NAFLD in the future. In this study, we conducted a preliminary assessment of the
      effect of SPX on hepatic lipogenesis by using the HepG2 cell line, derived from
      human liver cancer, as a model of the liver. SPX significantly suppressed the
      excess accumulation of triacylglycerol induced by liver X receptor alpha
      (LXRalpha) agonist by downregulating a nuclear transcription factor named sterol
      regulatory element-binding protein-1c and a set of related genes. Moreover, fatty
      acid translocase (CD36) and fatty acid-binding protein-1, which regulates fatty
      acid uptake, also exhibited significant decrease in transcriptional levels.
      Furthermore, we found that SPX blocked LXRalpha activation and would be a
      promising candidate for antagonist of LXRalpha.

PMID- 29446840
TI  - Uncontrolled blood pressure affects atrial remodeling and adverse clinical
      outcome in paroxysmal atrial fibrillation.
AB  - BACKGROUND: To investigate the impact of uncontrolled blood pressure (BP) on left
      atrial (LA) remodeling and clinical outcome after pulmonary vein isolation (PVI)
      in paroxysmal atrial fibrillation (AF). METHODS: One hundred and one symptomatic
      paroxysmal AF patients (85 males, 62.2 +/- 8.4-year-old) who underwent successful
      PVI were classified as follows: group 1 (n = 46), no hypertension (HTN); group 2
      (n = 36), HTN with controlled BP; and group 3 (n = 19), HTN with uncontrolled BP.
      Uncontrolled BP was defined as BP > 140/90 mm Hg. LA dimension was measured by
      echocardiography before and 6 months after PVI. LA wall thickness along the
      ablation line was measured using computed tomography prior to PVI. Cox regression
      analysis was performed for the prediction of recurrence. RESULTS: LA wall
      thickness in groups 2 and 3 was greater than that of group 1, except for the
      anterior right superior pulmonary vein (PV) and posterior left inferior PV.
      Kaplan-Meier analysis revealed a significantly higher recurrence in group 3
      (52.6%). LA dimension only increased in group 3 (38.2 +/- 5.6 mm to 41.3 +/- 6.2
      mm, P = 0.022). At the second procedure, all group 3 recurrent patients showed
      substrate degradation (low voltage area and/or dense scar formation) and required
      substrate modification. Uncontrolled BP was an independent risk factor for
      recurrence (hazard ratio: 2.350, P = 0.033). CONCLUSIONS: HTN induced
      heterogeneous LA hypertrophy regardless of whether HTN was controlled.
      Uncontrolled BP promoted atrial remodeling, and is therefore a strong predictor
      for recurrence of AF after PVI.

PMID- 29446841
TI  - The connection between the breast and heart in a woman: Breast cancer and
      cardiovascular disease.
AB  - Cardiovascular disease remains the leading cause of death in women in the United
      States and is a major public health issue for all women, but it is of increasing
      concern to breast cancer survivors. Advancements in early detection and breast
      cancer therapy have resulted in over 90% of women surviving 5 years past their
      diagnosis of breast cancer. Nonetheless, with increased survivorship from breast
      cancer, there has been an increase in cardiovascular disease in these women. The
      consequences of the treatments for breast cancer may increase the risk for
      cardiovascular disease. Additionally, there is an overlap of risk factors common
      to both breast cancer and cardiovascular disease. The increased risk of
      cardiovascular disease in women who survive breast cancer must be recognized,
      with a focus on the prevention and early detection of cardiovascular disease.

PMID- 29446842
TI  - Epidemiology and Risk Factors for Outpatient-Acquired Catheter-Related
      Bloodstream Infections in Children Receiving Home Parenteral Nutrition.
AB  - BACKGROUND: Few studies have examined the epidemiology and risk factors for the
      development of outpatient-acquired catheter-related bloodstream infections
      (CRBSIs) in children receiving home parenteral nutrition. This study aimed to (1)
      characterize the incidence, clinical presentation, and epidemiology of CRBSIs and
      (2) identify risk factors for CRBSIs in children receiving home parenteral
      nutrition. METHODS: A longitudinal database approved by our Institutional Review
      Board was created to prospectively track CRBSIs in the UCLA pediatric population
      from January to December 2012. Eligible patients included those < 18 years old
      receiving home parenteral nutrition. RESULTS: Thirty of 60 patients (50%) were
      diagnosed with 66 CRBSIs, for an overall CRBSI rate of 3.6 per 1000 catheter
      days. Of the CRBSIs, 73% were due to single microorganisms and 27% were
      polymicrobial. There was a significant difference in median (range) time for
      blood cultures to turn positive depending on type of CRBSIs (p = 0.03), with
      polymicrobial infections detected at 13.4 (8.7-24.3) hours, gram-negative
      infections at 16.5 (9-30.8) hours, and gram-positive infections at 18.9 (8.4
      37.1) hours. The most common presenting symptom was fever (82%), followed by
      gastrointestinal symptoms (42%) and chills (29%). The only significant
      multivariate risk factor for CRBSIs was presence of a feeding tube (2.3-fold
      increase in CRBSI risk, p = 0.04). DISCUSSION: Outpatient-acquired CRBSIs are
      common in children receiving home parenteral nutrition. CRBSIs typically present
      with fever, but are also associated with gastrointestinal and/or respiratory
      symptoms. The presence of feeding tubes may predispose children on home
      parenteral nutrition to developing CRBSIs.

PMID- 29446843
TI  - Characterization of ectopic myelinated nerve fibers in the retina of a cynomolgus
      monkey (Macaca fascicularis).
AB  - We report histopathology of retinal myelination discovered in a cynomolgus
      monkey. It consisted of a uniform population of spindle cells arranged in
      fascicles within the retina at the optic disk. The present case is remarkable in
      that there is a paucity of reports describing myelinated retinal nerve fibers in
      monkeys.

PMID- 29446844
TI  - You've come a long way, baby.

PMID- 29446845
TI  - Simultaneous determination of 10 kinds of biogenic amines in rat plasma using
      high-performance liquid chromatography coupled with fluorescence detection.
AB  - We describe a simple, rapid, selective and sensitive HPLC method coupled with
      fluorescence detection for simultaneous determination of 10 kinds of biogenic
      amines (BAs: tryptamine, 2-phenethylamine, putrescine, cadaverine, histamine, 5
      hydroxytryptamine, tyramine, spermidine, dopamine and spermine). BAs and IS were
      derivated with dansyl chloride. Fluorescence detection (lambdaex /lambdaem =
      340/510 nm) was used. A satisfactory result for method validation was obtained.
      The assay was shown to be linear over the ranges 0.005-1.0 MUg/mL for tryptamine,
      2-phenethylamine and spermidine, 0.025-1.0 MUg/mL for putrescine, 0.001-1.0
      MUg/mL for cadaverine, 0.25-20 MUg/mL for histamine, 0.25-10 MUg/mL for 5
      hydroxytryptamine and dopamine, and 0.01-1.0 MUg/mL for tyramine and spermine.
      The limits of detection and the limits of quantification were 0.3-75.0 ng/mL and
      1.0-250.0 ng/mL, respectively. Relative standard deviations were <=5.14% for
      intra-day and <=6.58% for inter-day precision. The recoveries of BAs ranged from
      79.11 to 114.26% after spiking standard solutions of BAs into a sample at three
      levels. Seven kinds of BAs were found in rat plasma, and the mean values of
      tryptamine, 2-phenethylamine, putrescine, cadaverine, histamine, spermidine and
      spermine determined were 52.72 +/- 7.34, 11.45 +/- 1.56, 162.56 +/- 6.26, 312.75
      +/- 18.11, 1306.50 +/- 116.16, 273.89 +/- 26.41 and 41.51 +/- 2.07 ng/mL,
      respectively.

PMID- 29446846
TI  - Histological immune response patterns in sentinel lymph nodes involved by
      metastatic melanoma and prognostic significance.
AB  - BACKGROUND: To further characterize the micromorphometric immunological pattern
      to metastatic melanoma in sentinel lymph node (SLN) biopsies and completion lymph
      node (CLN) dissections and their relation to 5-year overall survival (OS).
      METHODS: Retrospective cohort of 49 patients from 1996 to 2005 with a positive
      SLN who underwent CLN dissection (CLD) was studied. Micromorphometric
      characteristics included follicular center count (FCC)/profile, sinus
      histiocytosis, metastatic size, tumor infiltrating lymphocytes (intranodal),
      paracortical dendritic cells, germinal center reaction and morphology. Comparison
      of Kaplan-Meier survival curves used the exact log-rank statistic. RESULTS: In
      the high-FCC (n = 5-51) vs the low-FCC (n < 5) lymph nodes, a delayed separation
      occurred at 3 years, with 5-year OS rates being 73% vs 54% in the high- and low
      FCC groups, respectively. Improved survival up to 3 years was also noted in CLDs
      that showed a higher FCC when compared to the prior SLN. Patients with metastatic
      deposits >2 mm had significantly lower 5-year survival (both <.001). CONCLUSIONS:
      Nodal micromorphometric features (ie, FCC) are probably related to host immune
      response to metastasis. Quantitative evaluation of lymphoid follicular centers
      could provide valuable prognostic information to help to stratify patients.

PMID- 29446847
TI  - Lipidomic Analysis: From Archaea to Mammals.
AB  - Lipids are among the most important organic compounds found in all living cells,
      from primitive archaebacteria to flowering plants or mammalian cells. They form
      part of cell walls and constitute cell storage material. Their biosynthesis and
      metabolism play key roles in faraway topics such as biofuel production (third
      generation biofuels produced by microorganisms, e.g. algae) and human diseases
      such as adrenoleukodystrophy, Zellweger syndrome, or Refsum disease. Current
      lipidomic analysis requires fast and accurate processing of samples and
      especially their characterization. Because the number of possible lipids and,
      more specifically, molecular species of lipids is of the order of hundreds to
      thousands, it is necessary to process huge amounts of data in a short time. There
      are two basic approaches to lipidomic analysis: shotgun and liquid chromatography
      mass spectometry. Both methods have their pros and cons. This review deals with
      lipidomics not according to the type of ionization or the lipid classes analyzed
      but according to the types of samples (organisms) under study. Thus, it is
      divided into lipidomic analysis of archaebacteria, bacteria, yeast, fungi, algae,
      plants, and animals.

PMID- 29446848
TI  - Methodological issues in assessing the association between periodontitis and
      caries among adolescents.
AB  - OBJECTIVES: We aimed to investigate the association between dental caries and
      periodontitis among adolescents participating in a case-control study of
      periodontitis. In addition, we compared 2 analytical approaches to estimate the
      association: conventional regression and structural equation modelling (SEM).
      METHODS: Along with periodontal recordings, data were obtained on caries, just as
      subgingival plaque samples were collected. Sociodemographic information was
      collected with a questionnaire. We used factor analyses to express the many
      correlated clinical periodontal dimensions in a smaller number of factors. The
      association between caries (counts of enamel and dentin lesions, or dentin
      lesions only) and periodontitis was tested using negative binomial regression
      with robust variance (conventional regression) and weighted least squares (SEM)
      estimation. RESULTS: Factor analysis revealed 2 different latent periodontal
      variables: "extent" and "severity" of periodontitis. Using conventional
      regression, the "extent" of periodontitis was positively associated with higher
      counts of dentin caries lesions, even after adjustments for maternal education
      and subgingival microbial composition (rate ratio 1.34; 95% CI 1.07-1.68). The
      "severity" of periodontitis was associated with lower counts of enamel and dentin
      caries lesions (rate ratio 0.85 95% CI 0.77-0.92). The SEM revealed a positive
      association between periodontitis "extent" and number of dentin caries lesions
      (coefficient 0.29; P < .0001). The "severity" of periodontitis was negatively
      associated with enamel and dentin caries (coefficient -0.44; P < .0001).
      CONCLUSIONS: We found an association between caries and periodontitis among
      adolescents. The "severity" of periodontitis was negatively associated with
      enamel/dentin caries, whereas the "extent" of periodontitis was positively
      associated with dentin caries irrespective of the analytical approach employed.

PMID- 29446849
TI  - Anxiety and anger of homeless people coping with dental care.
AB  - OBJECTIVES: To reveal and describe from open-ended interviews how homeless people
      in Vancouver interpret, appraise and cope with dental care. METHODS: Audio
      recorded interviews with 25 homeless people (18 men and 7 women; age range: 25-64
      years), purposefully selected for a range of experiences, were transcribed and
      analysed inductively. The process of interpretive description drawing from the
      Behavioral Model for Vulnerable Populations and Lazarus's Theory of Emotions
      identified how participants appraised and coped with dental care. RESULTS: Four
      dominant themes emerged: barriers to care; service use; opinions on dental
      health; and improving dental services. Participants were anxious about the cost
      of dentistry and fearful of dentists. They got emergency dental care with
      difficulty, usually in hospital emergency departments although mostly they
      preferred self-treatment. They acknowledged the importance of dental health but
      felt stigmatized by their homelessness and visibly unhealthy mouths. They wanted
      accessible dental services with financial assistance from government, more
      widespread information about community dental clinics, and, notably among the
      Indigenous participants, less humiliating discrimination from dentists.
      CONCLUSIONS: Homeless people have difficulty coping with dental care. They
      believe that dentistry is frightening, humiliating and expensive, and governments
      are neither sympathetic to their disability nor willing to provide helpful
      information about community dental clinics or sufficient dental benefits for
      their needs.

PMID- 29446850
TI  - Superficial acral fibromyxoma in the heel with new vascular features on
      dermoscopy.
AB  - Superficial acral fibromyxoma (SAFM) is an uncommon mesenchymal soft tissue tumor
      with a predilection for the acral extremites and nail bed involvement. SAFM is
      diagnosed with clinicopathological and immunohistochemical examination. Awareness
      of this rare tumor is important because of amounts of benign and malignant
      neoplasms. We report a case of SAFM in a rare localization in the heel with a new
      finding on dermoscopy.

PMID- 29446851
TI  - Non-commercial vs. commercial clinical trials: a retrospective study of the
      applications submitted to a research ethics committee.
AB  - There are many difficulties in undertaking independent clinical research without
      support from the pharmaceutical industry. In this retrospective observational
      study, some design characteristics, the clinical trial public register and the
      publication rate of noncommercial clinical trials were compared to those of
      commercial clinical trials. A total of 809 applications of drug-evaluation
      clinical trials were submitted from May 2004 to May 2009 to the research ethics
      committee of a tertiary hospital, and 16.3% of trials were noncommercial. They
      were mainly phase IV, multicentre national, and unmasked controlled trials,
      compared to the commercial trials that were mainly phase II or III, multicentre
      international, and double-blind masked trials. The commercial trials were
      registered and published more often than noncommercial trials. More funding for
      noncommercial research is still needed. The results of the research, commercial
      or noncommercial, should be disseminated in order not to compromise either its
      scientific or its social value.

PMID- 29446852
TI  - Isolation of Crithidia spp. from lesions of immunocompetent patients with
      suspected cutaneous leishmaniasis in Iran.
AB  - OBJECTIVE: Leishmania major has been considered as the main etiological agent of
      cutaneous leishmaniasis in Iran. However, there are recent reports about
      existence of Crithidia spp in cutaneous lesions in southern Iran. Therefore, this
      study was designed to decipher some morphological, biological, and molecular
      aspects of this phenomenon. METHODS: Clinical isolates were obtained from 167
      patients with cutaneous ulcers. A set of specific primers based on GAPDH
      (Glyceraldehyde-3-Phosphate Dehydrogenase) gene were used to distinguish between
      Crithidia and Leishmania genera. For molecular analysis, Pulsed Field Gel
      Electrophoresis and Mi-Seq Illumina platform were applied. Then, morphological
      analysis and some biological features (including potential growth at 37  degrees
      C and the ability of infecting mammalian macrophages) were studied. RESULTS: In
      92.8% of clinical cases L. major was the only causative microorganism isolated,
      in 5.4% of cases co-infection of L. major and Crithidia spp. was identified, and
      in 1.8% of lesions only Crithidia spp. were found. CONCLUSION: We isolated
      Crithidia spp. from clinical samples of patients suspected of cutaneous
      leishmaniasis in Iran, indicating that Crithidia spp. are capable of surviving at
      human body temperature and infecting macrophage cells. This raises questions on
      the influence of this phenomenon on pathogenicity, therapeutic outcome, and
      disease control strategies. This article is protected by copyright. All rights
      reserved.

PMID- 29446853
TI  - Preclinical characterization of anlotinib, a highly potent and selective vascular
      endothelial growth factor receptor-2 inhibitor.
AB  - Abrogating tumor angiogenesis by inhibiting vascular endothelial growth factor
      receptor-2 (VEGFR2) has been established as a therapeutic strategy for treating
      cancer. However, because of their low selectivity, most small molecule inhibitors
      of VEGFR2 tyrosine kinase show unexpected adverse effects and limited anticancer
      efficacy. In the present study, we detailed the pharmacological properties of
      anlotinib, a highly potent and selective VEGFR2 inhibitor, in preclinical models.
      Anlotinib occupied the ATP-binding pocket of VEGFR2 tyrosine kinase and showed
      high selectivity and inhibitory potency (IC50 <1 nmol/L) for VEGFR2 relative to
      other tyrosine kinases. Concordant with this activity, anlotinib inhibited VEGF
      induced signaling and cell proliferation in HUVEC with picomolar IC50 values.
      However, micromolar concentrations of anlotinib were required to inhibit tumor
      cell proliferation directly in vitro. Anlotinib significantly inhibited HUVEC
      migration and tube formation; it also inhibited microvessel growth from explants
      of rat aorta in vitro and decreased vascular density in tumor tissue in vivo.
      Compared with the well-known tyrosine kinase inhibitor sunitinib, once-daily oral
      dose of anlotinib showed broader and stronger in vivo antitumor efficacy and, in
      some models, caused tumor regression in nude mice. Collectively, these results
      indicate that anlotinib is a well-tolerated, orally active VEGFR2 inhibitor that
      targets angiogenesis in tumor growth, and support ongoing clinical evaluation of
      anlotinib for a variety of malignancies.

PMID- 29446854
TI  - Overexpression of interleukin-35 in intrahepatic cholangiocarcinoma is a
      prognostic indicator after curative resection.
AB  - Interleukin-35 (IL-35) is implicated in tumorigenesis, but its exact impact on
      intrahepatic cholangiocarcinoma (ICC) is not clear. The aim of the present study
      was to explore the specific effect of IL-35 on patient prognosis. Additionally,
      we formulated an effective prognostic nomogram for ICC patients after curative
      resection. Immunohistochemistry was applied to explore IL-35 expression as well
      as IL-35 receptor (IL-35R) in 102 ICC patients. Results showed that IL-35 was
      highly expressed in ICC tumor tissues and was positively associated with lymph
      node metastasis (LNM), TNM stage and vascular invasion and was an independent
      prognostic factor for patients' overall survival (OS) and recurrence-free
      survival (RFS). High expression of IL-35R (gp130 and IL-12Rbeta2) was also
      observed in ICC cancer tissues, but only gp130 was an independent prognostic
      factor for OS and RFS and was indispensable in IL-35-mediated ICC clinical
      prognosis. The nomogram comprising carcinoembryonic antigen, LNM, IL-35 and gp130
      expression achieved better predictive accuracy compared with TNM stage for OS.
      Our data support that high IL-35 expression correlates with ICC aggressiveness
      and emerges as a valuable biomarker for evaluating ICC progression and prognosis
      in clinical work.

PMID- 29446856
TI  - Thyroid carcinoma producing beta-human chorionic gonadotropin shows different
      clinical behavior.
AB  - Columnar cell variant of papillary thyroid carcinoma (CCV-PTC) is an unusual
      neoplasm, the clinical behavior of which mainly depends on the encapsulation or
      infiltration. Patients with extensive extrathyroidal extension usually have an
      aggressive biological behavior. This study confirmed that beta-human chorionic
      gonadotropin (beta-hCG) secreting invasive CCV-PTC has good prognosis comparing
      with a cohort of follicular cell differentiated thyroid carcinoma. On the
      contrary, positive immunoreaction with beta-hCG was proved in three anaplastic
      thyroid carcinoma patients showing aggressive clinical courses. The
      clinicopathologic characteristics of CCV-PTC and the paraneoplastic syndromes in
      follicular cell differentiated thyroid carcinoma were further summarized using
      literature review.

PMID- 29446855
TI  - Associations Between Enteral Nutrition and Acute Respiratory Infection Among
      Patients in New York Metropolitan Region Pediatric Long-Term Care Facilities.
AB  - BACKGROUND: Pediatric long-term care facilities (pLTCF) serve a complicated and
      resource-intensive patient population with high usage of nutrition support.
      However, the relationship between nutrition support and outcomes among pLTCF
      residents is not well understood. We described this relationship in three
      metropolitan New York pLTCF and a subsample of infants from one of these
      facilities with a feeding disorders unit. METHODS: In this prospective cohort
      study, we used logistic regression to assess relationships between enteral
      nutrition (EN), and acute respiratory infections (ARI) among residents (n = 720,
      50% male, mean age = 5.5 years, mean number comorbidities = 2.1) and infant
      subsample (<1 year, n = 208, 50% male, mean number comorbidities = 2.0). We
      tested these associations in multivariable models controlling for numbers of
      comorbidities and infections. RESULTS: Many residents received nutrition via
      percutaneous (59%) or nasogastric (15%) feeding tubes. In univariate analyses,
      residents receiving EN had more comorbidities. In multivariable analyses, EN was
      associated with ARI (incidence rate ratio = 1.65, p < .001). Among infants in the
      specialized unit, greater risk of ARI was associated only with percutaneous
      (incidence rate ratio = 1.94, p < .01) feeding. EN was associated with lower odds
      of being discharged home (OR = 0.45, p < .01). CONCLUSION: The prevalence of EN,
      complexity of cases, and necessity of long-term EN make nutrition support
      important in pLTCFs. Differences in EN types and adverse outcomes in the infant
      subsample suggest different care is necessary for this subpopulation. Results
      provide context for improving quality of care and clinician/caregiver education
      for this population.

PMID- 29446857
TI  - Infectious risk of biological drugs vs. traditional systemic treatments in
      moderate-to-severe psoriasis: a cohort analysis in the French insurance database.
AB  - The aim of this study was to compare the infectious risk between a group of
      psoriasis patients treated by biological drugs (BD) and a group treated by
      traditional systemic treatments (TST). We built a retrospective observational
      cohort study from the French health insurance database in the Midi-Pyrenees area
      (2.9 million inhabitants, southwest of France) using data from 01/01/2010 to
      12/31/2013. We compared the infectious risk between 'exposed' patients treated
      with BD (adalimumab, etanercept, infliximab, or ustekinumab) and 'unexposed'
      patients treated by TST (phototherapy, acitretin, methotrexate, or cyclosporine).
      We realized a survival analysis on the first infectious event, defined as an anti
      infective drug delivery or a hospital diagnosis of infection. We selected 101
      'exposed' and 788 'unexposed' patients. In our multivariate Cox model, 'exposure'
      did not seem to decrease the time frame of the first infectious event compared
      with 'nonexposure' (HR = 0.94, P = 0.62). Among all treatment, the safest seemed
      to be ustekinumab while the least safe was etanercept. We found factors
      statistically associated with the risk of infection: gender (female vs. male),
      economic deprivation, chronic hepatitis B or C, history of cancer, at least one
      infectious event, and the number of different drugs during the 6-month period
      before the study. We did not find any difference of infective risk between the BD
      and the TST. This result enhances the recent PSONET registries conclusions.

PMID- 29446858
TI  - Enteral Nutrition for Pediatric Crohn's Disease: An Underutilized Therapy.
AB  - Enteral nutrition (EN) for the treatment of Crohn's disease (CD) involves
      administration of a liquid nutrition product, administered orally or through tube
      feeding, while excluding typical dietary components. It is a safe and effective,
      but largely underused, therapy in the United States as a treatment for CD. EN is
      a particularly attractive option for pediatric CD as it avoids side effects of
      corticosteroids, improves growth, and may have a higher likelihood of achieving
      mucosal healing than some traditional medications. However, there are multiple
      real and perceived barriers to its use among providers. A comprehensive approach
      to addressing these barriers to EN may result in its increased use. This paper
      reviews the literature on the efficacy of EN, methods of utilization, and
      potential barriers and solutions to those barriers.

PMID- 29446859
TI  - Dicyanamide Salts that Adopt Smectic, Columnar, or Bicontinuous Cubic Liquid
      Crystalline Mesophases.
AB  - Although dicyanamide (i.e., [N(CN)2 ]- ) has been commonly used to obtain low
      viscosity, halogen-free, room-temperature ionic liquids, liquid-crystalline salts
      containing such anions have remained virtually unexplored. Here we report a
      series of amphiphilic dicyanamide salts that, depending on their structures and
      compositions, adopt smectic, columnar, or bicontinuous cubic thermotropic liquid
      crystalline mesophases, even at room temperature in some cases. Their thermal
      properties were explored by polarized light optical microscopy, differential
      scanning calorimetry, thermogravimetric analysis (including evolved gas
      analysis), and variable-temperature synchrotron X-ray diffraction. Comparison of
      the thermal phase characteristics of these new liquid-crystalline salts featuring
      "V-shaped" [N(CN)2 ]- anions with those of structural analogues containing [SCN]-
      , [BF4 ]- , [PF6 ]- , or [CF3 SO3 ]- anions indicated that not only the size of
      the counterion but also its shape should be considered in the development of
      mesomorphic salts. Collectively, these discoveries may be expected to facilitate
      the design of thermotropic ionic liquid crystals that form inverted-type
      bicontinuous cubic and other sophisticated liquid-crystalline phases.

PMID- 29446860
TI  - Development of a clinical prediction rule for tuberculous meningitis in adults in
      Lima, Peru.
AB  - OBJECTIVES: Diagnosis of tuberculous meningitis (TM) is a challenge in countries
      with a high burden of the disease and constrained resources and clinical
      prediction rules (CPRs) could be of assistance. We aimed at developing a CPR for
      diagnosis of TM in a Latin American setting with high tuberculosis incidence and
      a concentrated HIV epidemic. METHODS: We enrolled adult patients with clinical
      suspicion of TM attending two hospitals in Lima, Peru. We obtained information on
      potential anamnestic, clinical and laboratory predictive findings that are easy
      to collect and promptly available. We independently diagnosed TM according to a
      composite reference standard that included a series of microbiological tests. We
      performed bivariate analysis and constructed a logistic regression model to
      select the predictive findings associated with TM. With the selected predictors
      included in the model, we developed a score-based CPR. We assessed its internal
      validity and diagnostic performance. RESULTS: Of 155 analysed patients, 59 (38%)
      had TM. The CPR we derived includes three predictors: cough for 14 days or more,
      10-500 cells in CSF and adenosine deaminase >= 6 U/l in CSF. It classifies
      patients into high-, moderate- or low-score groups and has an overall area under
      the ROC curve of 0.87. 59% of patients were assigned to either the high- or the
      low-score group, permitting prompt decision-making. In patients in the high-score
      group, it attains a positive likelihood ratio for TM of 10.6 and in patients with
      low scores, a negative likelihood ratio of 0.10. Bootstrap analysis indicated
      high internal validity. CONCLUSION: This CPR could support decision-making in
      patients with clinical suspicion of TM. External validation and further
      assessment of its clinical impact are necessary before application in other
      settings.

PMID- 29446861
TI  - Patterns of Posttraumatic Stress Disorder and Posttraumatic Growth Among
      Adolescents After the Wenchuan Earthquake in China: A Latent Profile Analysis.
AB  - Posttraumatic stress disorder (PTSD) and posttraumatic growth (PTG) often coexist
      in the survivors of traumatic events. The current study examined the coexisting
      patterns of PTSD and PTG using latent profile analysis in a sample of 591
      adolescent survivors of the May 12, 2008 Wenchuan earthquake in China. Logistic
      regression analysis was used to examine the effects of traumatic exposure on
      specific coexisting patterns. A three-class solution characterized by a growth
      group (39.6%), a low symptoms group (10.3%), and a coexistence group (50.1%)
      fitted the data best. Members of the low symptoms group were more likely to be
      male, odds ratio (OR) = 2.67, 95% CI [1.48, 4.81]; and adolescents in the
      coexistence group were more likely to be older, OR = 1.22, 95%CI [1.09, 1.37],
      and to have had experienced serious indirect exposure, OR = 1.07, 95% CI [1.02,
      1.12], and posttraumatic fear, OR = 1.20, 95% CI [1.11, 1.31].

PMID- 29446862
TI  - Primary enteric-type tubulovillous adenocarcinoma arising in the renal pelvis.

PMID- 29446863
TI  - Conservation value of low-productivity forests measured as the amount and
      diversity of dead wood and saproxylic beetles.
AB  - In many managed landscapes, low-productivity land comprises most of the remaining
      relatively untouched areas, and is often over-represented within protected areas.
      The relationship between the productivity and conservational value of a site is
      poorly known; however, it has been hypothesized that biodiversity increases with
      productivity due to higher resource abundance or heterogeneity, and that the
      species communities of low-productivity land are a nested subset of communities
      from more productive land. We tested these hypotheses for dead-wood-dependent
      beetles by comparing their species richness and composition, as well as the
      amount and diversity of dead wood, between low-productivity (potential forest
      growth <1 m3 .ha-1 .yr-1 ) and high-productivity Scots pine-dominated stands in
      Sweden. We included four stand types: stands situated on (1) thin soils and (2)
      mires (both low-productivity), (3) managed stands, and (4) unmanaged stands set
      aside for conservation purposes (both high-productivity). Beetle species richness
      and number of red-listed species were highest in the high-productivity set
      asides. Species richness was positively correlated with the volume and diversity
      of dead wood, but volume appeared to be a better predictor than diversity for the
      higher species richness in set-asides. Beetle species composition was similar
      among stand types, and the assemblages in low-productivity stands were largely
      subsets of those in high-productivity set-asides. However, 11% of all species and
      40% of red-listed species only occurred in high-productivity stands, while no
      species were unique to low-productivity stands. We conclude that low-productivity
      forests are less valuable for conservation than high-productivity forest land.
      Given the generally similar species composition among stand types, a comparable
      conservational effect could be obtained by setting aside a larger area of low
      productivity forest in comparison to the high-productivity. In terms of dead wood
      volumes, 1.8-3.6 ha of low-productivity forest has the same value as 1 ha of
      unmanaged high-productivity forest. This figure can be used to estimate the
      conservation value of low-productivity forests; however, as high-productivity
      forests harbored some unique species, they are not completely exchangeable.

PMID- 29446864
TI  - Sensitive and Specific Guest Recognition through Pyridinium-Modification in
      Spindle-Like Coordination Containers.
AB  - An elaborately designed pyridinium-functionalized octanuclear zinc(II)
      coordination container 1-Zn was prepared through the self-assembly of Zn2+ , p
      tert-butylsulfonylcalix[4]arene, and pyridinium-functionalized angular flexible
      dicarboxylate linker (H2 BrL1). The structure was determined by a single-crystal
      X-ray diffractometer. 1-Zn displays highly sensitive and specific recognition to
      2-picolylamine as revealed by drastic blueshifts of the absorption and emission
      spectra, ascribed to the decrease of intramolecular charge transfer (ICT)
      character of the container and the occurrence of intermolecular charge transfer
      between the host and guest molecules. The intramolecular charge transfer plays a
      key role in the modulation of the electronic properties and is tunable through
      endo-encapsulation of specific guest molecules.

PMID- 29446865
TI  - Guidance on the use of probiotics in clinical practice in children with selected
      clinical conditions and in specific vulnerable groups.
AB  - AIM: The use of probiotics has been covered by many guidelines, position papers
      and evidence-based recommendations, but few have referred to specific patient
      groups or clinical indications. This review summarises recommendations and
      scientifically credited guidelines on the use of probiotics for children with
      selected clinical conditions and provides practice points. METHODS: An expert
      panel was convened by the European Paediatric Association in June 2017 to define
      the relevant clinical questions for using probiotics in paediatric health care
      and review and summarise the guidelines, recommendations, position papers and
      high-quality evidence. RESULTS: The panel found that specific probiotic strains
      were effective in preventing antibiotic-associated and nosocomial diarrhoea,
      treating acute gastroenteritis and treating infantile colic in breastfed infants.
      However, special caution is indicated for premature infants, immunocompromised
      and critically ill patients and those with central venous catheters, cardiac
      valvular disease and short-gut syndrome. This review discusses the safety of
      using probiotics in selected groups of paediatric patients and the quality of the
      available products providing practice points based on proved findings.
      CONCLUSION: Efficacy of probiotics is strain specific. Their benefits are
      currently scientifically proven for their use in selected clinical conditions in
      children and not recommended for certain patient groups.

PMID- 29446867
TI  - Epigallocatechin Gallate Reduces Amyloid beta-Induced Neurotoxicity via
      Inhibiting Endoplasmic Reticulum Stress-Mediated Apoptosis.
AB  - SCOPE: We investigated the role of endoplasmic reticulum (ER) stress in the
      protective effects of EGCG against the neuronal apoptosis in Abeta1-42 -induced
      SH-SY5Y cells and APP/PS1 transgenic mice. METHODS AND RESULTS: Cell viability
      (CCK8 assay), flow cytometry, Hoechst 33258 staining, immunohistochemistry,
      transmission electron microscopy (TEM), and western blotting were used. EGCG
      prevented Abeta1-42-induced toxicity in SH-SY5Y cells, increased cell viability,
      and decreased apoptosis in a dose-dependent manner. In a subsequent mechanism
      study, it was found that this effect contributed to the down-regulation of GRP78,
      CHOP, cleaved-caspase-12 and -3. Moreover, EGCG also reduced the cytotoxicity
      induced by tunicamycin (TM) and thapsigargin (TG), two ER stress activators.
      Consistent with the in vitro study, EGCG inhibited neuronal apoptosis in the
      cortex of APP/PS1 transgenic mice, with the mitigation of ER abnormal
      ultrastructural swelling and the downregulation of ER-stress-associated proteins.
      CONCLUSION: These results indicate that EGCG attenuates the neurotoxicity in
      Alzheimer's disease (AD) via a novel mechanism that involves inhibition of ER
      stress-associated neuronal apoptosis in vitro and in vivo, suggesting the
      tremendous potential of EGCG for use in a nutritional preventive strategy against
      AD.

PMID- 29446868
TI  - Amyloid Polymorphism in the Protein Folding and Aggregation Energy Landscape.
AB  - Protein folding involves a large number of steps and conformations in which the
      folding protein samples different thermodynamic states characterized by local
      minima. Kinetically trapped on- or off-pathway intermediates are metastable
      folding intermediates towards the lowest absolute energy minima, which have been
      postulated to be the natively folded state where intramolecular interactions
      dominate, and the amyloid state where intermolecular interactions dominate.
      However, this view largely neglects the rich polymorphism found within amyloid
      species. We review the protein folding energy landscape in view of recent
      findings identifying specific transition routes among different amyloid
      polymorphs. Observed transitions such as twisted ribbon->crystal or helical
      ribbon->nanotube, and forbidden transitions such helical ribbon->crystal, are
      discussed and positioned within the protein folding and aggregation energy
      landscape. Finally, amyloid crystals are identified as the ground state of the
      protein folding and aggregation energy landscape.

PMID- 29446866
TI  - Tacrolimus concentration to dose ratio in solid organ transplant patients treated
      with fecal microbiota transplantation for recurrent Clostridium difficile
      infection.
AB  - Fecal microbiota transplantation (FMT) is increasingly being performed for
      Clostridium difficile infection in solid organ transplant (SOT) patients;
      however, little is known about the potential pharmacokinetic or pharmacomicrobial
      effects this may have on tacrolimus levels. We reviewed the medical records of 10
      SOT patients from September 2012-December 2016 who were taking tacrolimus at time
      of FMT for recurrent C. difficile infection. We compared the differences in
      tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months
      after FMT. The mean of the differences in C/D ratio calculated as
      (ng/mL)/(mg/kg/d) was -17.65 (95% CI -1.25 to 0.58) (ng/mL)/(mg/kg/d), P-value
      .43 by Wilcoxon signed-rank test. The mean of the differences in C/D ratio
      calculated as (ng/mL)/(mg/d) was -0.33 (95% CI -1.25 to 0.58) (ng/mL)/(mg/d), P
      value .28 by Wilcoxon signed-rank test. Of these patients, 2/10 underwent
      allograft biopsy for allograft dysfunction in the year after FMT, with no
      evidence of allograft rejection on pathology. These preliminary data suggest that
      FMT may not predictably alter tacrolimus levels and support its safety for SOT
      patients however further study in randomized trials is needed.

PMID- 29446869
TI  - Dimensions of the medial wall of the prelacrimal recess.
AB  - BACKGROUND: Addressing anterior maxillary sinus pathology endoscopically that is
      inaccessible with an endoscopic modified medial maxillectomy requires either a
      prelacrimal approach (PLA) or an endoscopic Denker's approach (EDA). The PLA
      involves removing the medial wall of the prelacrimal recess (PLR), which is the
      bone between the pyriform aperture (PA) and nasolacrimal duct (NLD), from nasal
      floor to orbital floor. The PLA preserves the inferior turbinate and NLD, whereas
      both are sacrificed during an EDA. The purpose of this computed tomography (CT)
      based study was to determine the anteroposterior and superoinferior dimensions of
      the medial wall of the PLR. METHODS: One hundred thirty-one triplanar sinus CT
      scans of patients with various rhinologic diseases, but with intact bony PLR
      walls, were reviewed to assess dimensions of the medial wall of the PLR. The
      anteroposterior distances from the PA to the inferior-most, middle, and superior
      most aspects of the NLD were measured. The height from the nasal floor to orbital
      floor was also measured. Combining left and right sides, there were 262
      measurements. RESULTS: The anteroposterior distances between the PA and the NLD
      were as follows: inferior: mean, 8.4 mm (standard error [SE], 0.2; range, 1.9
      14.2); middle: mean, 7.6 mm (SE, 0.2; range, 0-13.6); and superior: mean, 5.5 mm
      (SE, 2.5; range, 0-11.9). The mean height of the medial wall of the PLR was 26.5
      mm (SE, 0.2; range, 18.5-39.9). CONCLUSION: The anteroposterior and
      superoinferior dimensions of the medial wall of the PLR are variable, with the
      anteroposterior dimension being widest inferiorly. Its dimensions should be
      evaluated preoperatively when considering endoscopic approaches to or through the
      anterior maxillary sinus.

PMID- 29446870
TI  - Confinement Effects on the Benzene Orientational Structure.
AB  - Liquids under confinement exhibit different properties compared with their
      corresponding bulk phases, for example, miscibility, phase transitions, and
      diffusion. The underlying cause is the local ordering of molecules, which is
      usually only studied using pure simulation methods. Herein, we derive
      experimentally the structure of benzene confined in MCM-41 using total neutron
      scattering measurements. The study reveals a layering of molecules across a pore,
      and four concentric cylindrical shells can be distinguished for a pore with the
      radius of 18 A. The nanoscale confinement of the liquid has a major effect on the
      spatial and orientational correlations observed between the molecules, when
      compared with the structure of the bulk liquid. These differences are most marked
      for molecules in parallel configurations, and this suggests differences in
      chemical reactivity between the confined and bulk liquids.

PMID- 29446872
TI  - Does selective hormesis impact herbicide resistance evolution in weeds? ACCase
      resistant populations of Alopecurus myosuroides Huds. as a case study.
AB  - BACKGROUND: A field-evolved herbicide-resistant weed population can represent a
      heterogeneous composite of subpopulations that differ in their susceptibility and
      responsiveness to herbicide hormesis. Variable hormesis responsiveness can result
      in selection for and against certain subpopulations under low herbicide doses,
      and this has the potential to contribute to the evolution of resistance. The
      relevance of this hypothesis at practical field rates was studied for two field
      collected acetyl-coenzyme A carboxylase (ACCase) target-site resistant (TSR)
      biotypes of Alopecurus myosuroides Huds. (haplotype Leu1781) exposed to three
      ACCase inhibitors. Herbicide dose responses were evaluated at the population
      level and at different subpopulation levels after the dissection of individual
      plants by herbicide selection and genotyping. RESULTS: The practical field rates
      of fenoxaprop-P were lower than the observed hormetic doses in the resistant
      subpopulation, whereas the field rates of clodinafop and cycloxydim stimulated
      the shoot biomass in different resistant subpopulations by 21-38% above that of
      the control. Because variable dose levels induced hormesis in the different
      subpopulations, the practical field rates showed a significant potential to
      selectively enhance parts of a resistant field population, but did not impact or
      adversely affect other parts of the population. CONCLUSION: As a consequence of
      population heterogeneity, herbicide hormesis may impact resistance evolution in
      weeds at realistic use rates via the selective promotion of individual genotypes.
      However, the practical relevance of this phenomenon may be influenced by many
      factors, such as the herbicidal active ingredient used, as indicated in this
      study. (c) 2018 Society of Chemical Industry.

PMID- 29446871
TI  - Effect of management of organic wastes on inactivation of Brassica nigra and
      Fusarium oxysporum f.sp. lactucae using soil biosolarization.
AB  - BACKGROUND: Soil biosolarization is a promising alternative to conventional
      fumigation. Volatile fatty acids (VFAs) produced in the soil through fermentation
      of amended organic matter can affect pest inactivation during biosolarization.
      The objective was to determine how soil amended with organic wastes that were
      partially stabilized through either composting or anaerobic digestion affected
      the inactivation of Brassica nigra (BN; a weed) and Fusarium oxysporum f. sp.
      lactucae (FOL; a phytopathogenic fungus). RESULTS: The mortality of BN seeds in
      the biosolarized soil was 12% higher than in the solarized soil, although this
      difference was not significant. However, a significant correlation between BN
      mortality and VFA accumulation was observed. The number of FOL colony-forming
      units (CFU) in solarized samples at 5 cm was 34 CFU g-1 of soil, whereas in the
      biosolarized samples levels were below the limit of quantification. At 15 cm,
      these levels were 100 CFU g-1 for solarized samples and < 50 CFU g-1 of soil for
      the biosolarized samples. Amendment addition positively affected the organic
      matter and potassium content after the solarization process. CONCLUSION: The
      organic waste stabilization method can impact downstream biosolarization
      performance and final pest inactivation levels. This study suggests that organic
      waste management practices can be leveraged to improve pest control and soil
      quality. (c) 2018 Society of Chemical Industry.

PMID- 29446873
TI  - Laser stimulating ST36 with optical fiber induce blood component changes in mice:
      a Raman spectroscopy study.
AB  - ST36 is a commonly-used acupoint in traditional Chinese medicine (TCM) for
      treatment of inflammations, pains and gastrointestinal disturbs. For decades, the
      low power laser acupuncture has been widely applied as an alternative therapy to
      traditional metal needle acupuncture and achieved relatively fine therapeutic
      effect for ST36-related symptoms with reduction of uncomfortableness and
      infection risks. However its disadvantages of low penetrativity and lack of
      manipulation skills limit its potential performance. An optical fiber laser
      acupuncture introduced by the previous study combines traditional needling
      acupuncture and the laser stimulation together, making a stronger therapeutic
      effect and showing a potential value in clinical application. To evaluate its
      acupunctural effect on blood, mice are taken as experimental model and Raman
      spectroscopic technique is used to analysis the changes of blood components after
      stimulating on ST36. The results show that both the traditional needling
      acupuncture and optical fiber acupuncture could lead to some spectral changes of
      blood in mice. This study explores the optical fiber acupuncture's effect on
      blood in mice using Raman spectroscopy technique for mechanism of acupuncture
      therapy.

PMID- 29446874
TI  - Transplant recipients are vulnerable to coverage denial under Medicare Part D.
AB  - Transplant immunosuppressants are often used off-label because of insufficient
      randomized prospective trial data to achieve organ-specific US Food and Drug
      Administration (FDA) approval. Transplant recipients who rely on Medicare Part D
      for immunosuppressant drug coverage are vulnerable to coverage denial for off
      label prescriptions, unless use is supported by Centers for Medicare & Medicaid
      Services (CMS)-approved compendia. An integrated dataset including national
      transplant registry data and 3 years of dispensed pharmacy records was used to
      identify the prevalence of immunosuppression use that is both off-label and not
      supported by CMS-approved compendia. Numbers of potentially vulnerable transplant
      recipients were identified. Off-label and off-compendia immunosuppression
      regimens are frequently prescribed (3-year mean: lung 66.5%, intestine 34.2%,
      pancreas 33.4%, heart 21.8%, liver 16.5%, kidney 0%). The annual retail cost of
      these at-risk medications exceeds $30 million. This population-based study of
      transplant immunosuppressants vulnerable to claim denials under Medicare Part D
      coverage demonstrates a substantial gap between clinical practice, current FDA
      approval processes, and policy mandates for pharmaceutical coverage. This
      coverage barrier reduces access to life-saving medications for patients without
      alternative resources and may increase the risk of graft loss and death from
      medication nonadherence.

PMID- 29446875
TI  - Nickel-Catalyzed Umpolung Arylation of Ambiphilic alpha-Bromoalkyl Boronic
      Esters.
AB  - A nickel-catalyzed reductive arylation of ambiphilic alpha-bromoalkyl boronic
      esters with aryl halides is described. This platform provides an unrecognized
      opportunity to promote the catalytic umpolung reactivity of ambiphilic reagents
      with aryl halides, thus unlocking a new cross-coupling strategy that complements
      existing methods for the preparation of densely functionalized alkyl-substituted
      organometallic reagents from simple and readily accessible precursors.

PMID- 29446876
TI  - Ecosystem services rather than designated uses should be the backbone of United
      States Clean Water Act programs.

PMID- 29446878
TI  - Communicating environmental sciences: Public discourse and policy development.

PMID- 29446879
TI  - Sibling rivalry, peace, love, and environmental debate in the 21st century.

PMID- 29446880
TI  - Challenges associated with performing environmental research on titanium dioxide
      nanoparticles in aquatic environments.

PMID- 29446882
TI  - Learned Discourses: Timely Scientific Opinions.

PMID- 29446881
TI  - "Zweckoptimismus" and the Paris process will not save the world from climate
      catastrophe.
AB  - Politicians, government officials, business representatives, and nongovernmental
      climate activists all in various ways emphasize what they see as progress being
      made in the aftermath of the Paris Agreement, even if they continue to warn of
      the dire consequences of business as usual. Indeed, there is no lack of
      encouraging private and public sector initiatives on climate change. Some macro
      trends seem to be moving in the right direction, as well. But, closer scrutiny
      shows that these positive trends are still far from adding up to the necessary
      fundamental shift in the global energy economy. Furthermore, the public may
      greatly overestimate the advancement of renewable solar and wind energy
      technology, which contributes to a false sense of progress and lessens political
      urgency. Without determined and reinvigorated political leadership from the
      European Union (EU), there is little hope that necessary emission reduction goals
      to stay below 2  degrees C above preindustrial levels can be met. The EU has
      driven international climate policy from the beginning of climate negotiations,
      and there is unfortunately no other source of leadership in sight. It will
      require difficult political decisions to be taken sooner rather than later to
      force a much quicker domestic energy transition and to raise financing to help
      developing countries with their own energy transition and adaptation to a rapidly
      warming world. Integr Environ Assess Manag 2018;14:198-201. (c) 2018 SETAC.

PMID- 29446883
TI  - When resistance gene pyramids are not durable-the role of pathogen diversity.

PMID- 29446884
TI  - The Depression Connection. Diabetes and depression are linked. Could stress be
      the culprit?

PMID- 29446885
TI  - Fit O'clock. Timing your workout to avoid blood glucose highs and lows.

PMID- 29446886
TI  - Mind Your Meds Mind your Meds. Forgot to take your meds again? Stay on schedule
      with these tried-and-true tips.

PMID- 29446887
TI  - Out in the Open. Talk to your doctor about your uh-oh health issues.

PMID- 29446888
TI  - Ready to Retire. Planning ahead makes for a smooth transition from nine-to-fiver
      to retiree.
AB  - Many people look forward to retirement after decades of work, while others may
      find themselves there unexpectedly. Either way, it's a big transition. But with a
      little planning, you can protect your health as you move into this new phase of
      life with diabetes.

PMID- 29446889
TI  - Marriage diabetes style. Couples who manage together stay together.

PMID- 29446890
TI  - Building a better pancreas.
AB  - For years, an artificial pancreas was a pipe dream. Now, we're closer than ever
      to systems that will automatically adjust background insulin. Here's what's in
      the works--and what's still to come.

PMID- 29446891
TI  - Learning Curve.

PMID- 29446893
TI  - Diagnosis: Alzheimer's Disease.

PMID- 29446892
TI  - Double diagnosis. How to manage diabetes another life-changing condition.

PMID- 29446894
TI  - The Low-Carb Craze.

PMID- 29446895
TI  - [Effects of locomotor training and functional electrical stimulation on postural
      function in children with severe cerebral palsy].
AB  - Cerebral palsy (CP) considerably impairs the ability to maintain upright stance.
      In the present study the effects of locomotor training and functional electrical
      stimulation (FES) on postural control have been determined in children (n = 27)
      aged 6-12 years with severe CP. The severity level of the CP clinical
      manifestations was determined as 3 according to the Gross Motor Function
      Classification System (GMFCS) classification. All patients participated in 15
      half-hour sessions of mechanic therapy using robot-assisted passive stepping. In
      12 out of 27 children, the locomotion therapy was accompanied with FES.
      Stabilometry and plantography tests were performed before and after the course of
      interventions.  In addition, similar posturographics tests were performed in 23
      healthy children same age. Postural control in children with CP was characterized
      by a forward shift of the center of pressure (COP) projection; higher values of
      the COP trajectory area and length, as weel as by mean amplitude of the COP
      oscillations, and the absence of COP response to the eyes closed condition. After
      treatment, the posturographic characteristics had a tendency to normalization in
      relation to the values obtained in neurologically intact children. The
      improvement was observed in 43% of children without FES and in 75% of children
      which used FES. Analysis of plantograms revealed normalization of footprints in
      children received FES. Thus, it was demonstrated that FES combined with locomotor
      training resulted in the improvement in vertical posture control in children with
      severe CP.

PMID- 29446896
TI  - [Features of Parkinsonian and essential tremor of the human hand].
AB  - Using spectral, wavelet, multifractal, and recurrence analyses we examined the
      features of involuntary shaking (tremor) arising during the performance of a
      given motor task. The task was to maintain the efforts of fingers under isometric
      conditions by a healthy subject, a patient with primary bilateral parkinsonism,
      and a patient with a syndrome of the essential tremor. The physiological tremor
      was characterized by the minimal amplitude, the broad power spectrum, the minimal
      energy of the wavelet spectrum, the maximal degree of multifractality, the
      minimal degree of determinism, and the maximal entropy of recurrence time
      density. In the case of the essential tremor we observed the significant
      enhancement of the wavelet spectrum energy and the decrease of the oscillation
      complexity. It was evident as the appearance of clear peaks in the power spectra,
      the fall in the multifractality degree, the emergence of a quasiperiodic
      structure in the recurrence diagrams, the grow of determinism and the decrease of
      the entropy of recurrence time density. All these trends were enhanced for the
      parkinsonian tremor. The suggested characteristics enable us to estimate the
      degree of deviation of the motor function from the healthy one.

PMID- 29446897
TI  - [Cortical functional connectivity during retention of affective pictures in
      working memory: EEG-source theta coherence analysis].
AB  - A pattern of cortical functional connectivity in the source space was studied in
      a group of right-handed adult participants (N = 44:17 women, 27 men, aged M =
      29.61 +/- 6.45 years) who retained in their working memory (WM) traces of
      realistic pictures of positive, neutral, and negative emotional valence while in
      their working memory (WM) while performing same different task in which
      participants had to compare an etalon picture against a target picture that
      followed after a specified delay. A coherence (COH) between pairs of cortical
      sources chosen in advance according to fMRI data was estimated in the theta
      frequency range for the period of time preceding the etalon stimulus, distinct
      sets of functional links are found. The links of the first type that presumably
      reflect the involvement of sustained attention were between the dorsal anterior
      cingulate cortex, the prefrontal areas, and temporal areas of the right
      hemispheres. When compared to the rest period, links of this type showed
      strengthening not only during the retention period but also during the period
      preceding the etalon picture. The links of the second type presumably reflecting
      a progressive neocortex-to-hippocampus functional integration with increasing
      memory load and strengthened exclusively during retention period. Those links
      were between parietal, temporal and prefrontal cortices in the lateral surface of
      both hemispheres with the additional inclusion of the posterior cingulate cortex
      and the medial parietal cortex in the left hemisphere. An impact of emotional
      valence onto the strength and topography of the functional links of the second
      type was found. In the left hemisphere, an increase in the strength of cortical
      interaction was more pronounced for pictures of positive valence than for
      pictures of either neutral or negative valences. When compared to the pictures of
      neutral valence, the retention of pictorial information of both positive and
      negative valence showed some extraneous integration of the cortical areas for the
      theta rhythm. This finding might be related to the additional load exerted by
      emotionally colored pictures onto the mechanisms of short-time retention of
      visual information.

PMID- 29446898
TI  - [Features of invariant recognition of visual objects in preschool children with
      typical and atypical development].
AB  - We studied the ability of invariant recognition of the form of visual images
      concerning color, size and location of the image in 5-6 year-old children with
      typical and atypical patterns of development.  It was found that the children of
      this age with typical development are able to identify the invariant form of a
      visual object regardless of any changes in its color, size or location.  Children
      with neurodevelopmental disorders have difficulties with identifying the form of
      a visual object when its location is changed among a large number of figures.  In
      children with early infantile autism, we observed different degrees of visual
      perception deficit.  Children with milder forms of autistic disorders have
      difficulties only with recognizing the forms of an image when its location is
      changed; children with more severe forms of disorders, we observed serious
      disability of invariant recognition regardless of the color, size and location of
      images.

PMID- 29446899
TI  - [Visual-manual tracking after long spaceflight].
AB  - This study presents the results of the pre- and postflight clinical and
      physiological examination (CPE) and scientific experiment "Sensory Adaptation-2"
      carried out in Yu.A. Gagarin Research & Test Cosmonaut Training Center.  There
      were examined 14 Russian cosmonauts, crewmembers of long-term international
      spaceflights ISS-28/29 to ISS 36/37, who were in microgravity from 159 to 195
      days. Age of the cosmonauts was 35-50 years. Studies were conducted twice before
      space flight (baseline), and on days R+1(2), R+4(5), and R+8(9) after landing. 
      In the study of visual-manual tracking (VMT), eye movements were recorded by the
      electrooculography method (EOG), hand movements - by a joystick using biological
      visual feedback (on the screen represented the current angle/position of a
      joystick). Examinations were conducted using computerized stimulation programs,
      which were presented on the screen of the hardware-software complex "Sensomotor".
      Examinations of the VMT took place in the dialog mode and included the following
      sections: a) EOG-calibration; b) visual-manual tracking within +/-10 degrees  on
      the screen with blank background (smooth linear and sinusoidal movement of a
      point target with a frequency of 0.16 Hz in the vertical and horizontal
      directions). There were evaluated time, amplitude, and velocity characteristics
      of visual and manual tracking (VT and MT), including the effectiveness (EC) and
      gain (GC) coefficients which were calculated respectively, as the ratio of
      amplitude and velocity of the visual stimulus (target). A study of the vestibular
      function (VF) was performed before and after space flight using videooculography.
      There were assessed static torsion otolith-cervical-ocular reflex, dynamic
      vestibular-cervical-ocular reactions, vestibular reactivity, spontaneous eye
      movements. Study of VF in the first postflight has shown a sharp decrease (up to
      its complete absence) of static vestibular excitability (otolith reflex)
      accompanied by the increased dynamic reactivity of the vestibular system. Study
      of VTM has shown a significant decrease of gain and effectiveness/amplitud of VT
      in the first days postflight, as well as correlation between the parameters of VF
      and MT, between the VF and VT, and no found correlation between parameters of VF
      and MT.  It was found that the conditions of space flight (microgravity) have a
      greater impact on the accuracy of the VT than the accuracy of MT. Full return of
      characteristics of the VMT and VF to the baseline was observed on R+8(9) days
      after space flight.

PMID- 29446900
TI  - [Noise affect to the fragmented contour image recognition].
AB  - We performed a comparison of the results of recognition of fragmented outline
      images in the presence of noise and without it.  Contour images and visual noise
      were synthesized form Gabor elements.  Distances between the Gabor elements in
      contour and in noise were changed and image sizes varied too.  The percentage of
      correct responses was not dependent on the size of the stimuli, but differed for
      the same objects in the noise and without noise.  The percentage of recognition
      was higher for images with lots of turns in case without noise.  The recognition
      in noise was better for contour images having lines with slightly varying
      curvature.  Identification in noise depended on the ration of the distances
      between the elements in noise and in contour.

PMID- 29446901
TI  - [Severity of depressive symptoms and oscillatory responses to emotional facial
      expressions].
AB  - We studies the differences in oscillatory responses to emotional facial
      expressions in 40 subjects with different severity of depressive symptoms (19 men
      and 21 women) aged 18-30 years.  In subjects with low severity of depressive
      symptoms (group 2), the perception of happy facial expressions was marked by
      lower delta synchronization as compared with angry and neutral expressions; in
      subjects with high severity of depressive chronization as compared with angry and
      neutral expression; in subjects with high severity of depressive symptoms (group
      1), the perception of happy faces was marked by higher delta synchronization. 
      Since an increase in delta oscillations is usually observed in aversive
      conditions, we suggest that happy facial expressions are perceived as negative
      stimuli by the subjects of group 1.  The perception of angry facial expressions
      was accompanied by alpha band desynchronization in Group 2 and by alpha
      synchronization in Group 1.  Basing on Klimesch's theory, this effect suggests
      that the subjects of group 1 are initially set up for the perception of negative
      emotional information.  The effect of emotional stimulus category was significant
      in group 2, but not significant in group 1, which is an evidence of disorders in
      the recognition of emotional information in depression-prone individuals.

PMID- 29446903
TI  - President's Page: Be Grateful.

PMID- 29446902
TI  - Turning out the lights for Rural Medicine.

PMID- 29446908
TI  - [Physiological mechanisms of simulated purposeful activities in patients with
      epilepsy].
AB  - We examined 102 patients with symptomatic, cryptogenic, and idiopathic forms of
      epilepsy in order to investigate the physiological mechanisms providing the
      efficiency of purposeful activity in patients with this disease.  Three clusters
      of patients were formed with the use of the Gorbov-Shulte performance test.  The
      patients of "low efficiency" cluster were characterized by the lack of
      habituation mechanisms in the activity of afferent systems and mechanism of motor
      response; the activity rate of stress adaptation systems and the rate of
      intrasystemic tension during the preparation to purposeful activities were higher
      than in patients of "intermediate" and "high performance" clusters.

PMID- 29446909
TI  - [Association between G/A - Polymorphism of EPAS1 gene and the maximal level of
      oxygen consumption in Russian athletes.
AB  - We studied the interrelations between G/A-polymorphism of EPAS 1 gene(rs1867785)
      and macimal oxygen consumption  (VO2max) in Russian male athletes.  There were
      two groups in the study: athletes of different sport specialization (n = 241) and
      nonathletic males (n = 92).  It was found that the frequency of AA and AG
      genotype of EPAS1 gene in the group of athletes was higher (chi2 = 14.16, p =
      0.03).  In the subgroups with average (EPAS1*A 38.1% and EPAS1*G 61.9%) and high
      ((EPAS1*A 41.8% and EPAS1*G 58.2%) VO2max values, the frequency of these alleles
      was significantly different from those in the control group (chi2 = 7.53, p =
      0.006 and chi2 = 6.58, p = 0.01, respectively).  This suggests that higher
      aerobic capacities are caused by the presence of at least one minor A-Allele of
      the EPAS1 gene in the genome of an athlete.

PMID- 29446910
TI  - [Sex differences in the association between 25-hydroxyvitamin D and serum blood
      lipids in health youth.
AB  - Correlations of 25-hydroxyvitamin D, or 25(OH)D, serum concentration with the
      blood levels of total cholesterol (TC), high-density lipoprotein cholesterol,
      triglycerides (TG), and apolipoprotein E were analyzed in young non-overweight
      men (n = 40) and females (n = 61) aged 14-23 having no excess body mass. The
      measured variables have been standardized within each of four locality groups.
      The spearman rank correlation coefficients of 25(OH)D were Rsp = 0.306 (p =
      0.017) with TC in females, and Rsp =-0.372 (p = 0.018).

PMID- 29446911
TI  - [Physiological basis of alcohol-induced skeletal muscle injury].
AB  - Alcohol-induced muscle damage (AIMD) - an umbrella term that includes all forms
      of alcoholic myopathy developing in acute or chronic alcohol intoxication.  The
      most common form of destruction of skeletal muscle in alcoholism is a chronic
      alcoholic myopathy, which develops independently of other manifestations of
      alcoholism, such as polyneuropathy, malabsorption syndrome, liver damage, but can
      be combined with them.  The basis of the destruction of skeletal muscle in
      chronic AIPM is atrophy of muscle fibers.  Mainly affects muscle fiber type II
      with less destruction of type ! fibers.  Currently, the pathogenesis of chronic
      alcoholic myopathy is studied.  The imbalance of protein synthesis and
      proteolysisand increased apoptosis rate are discussed.

PMID- 29446912
TI  - Cathodic Corrosion of a Bulk Wire to Nonaggregated Functional Nanocrystals and
      Nanoalloys.
AB  - A key enabling step in leveraging the properties of nanoparticles (NPs) is to
      explore new, simple, controllable, and scalable nanotechnologies for their
      syntheses. Among "wet" methods, cathodic corrosion has been used to synthesize
      catalytic aggregates with some control over their size and preferential faceting.
      Here, we report on a modification of the cathodic corrosion method for producing
      a range of nonaggregated nanocrystals (Pt, Pd, Au, Ag, Cu, Rh, Ir, and Ni) and
      nanoalloys (Pt50Au50, Pd50Au50, and Ag xAu100- x) with potential for scaling up
      the production rate. The method employs poly(vinylpyrrolidone) (PVP) as a
      stabilizer in an electrolyte solution containing nonreducible cations (Na+,
      Ca2+), and cathodic corrosion of the corresponding wires takes place in the
      electrolyte under ultrasonication. The ultrasonication not only promotes particle
      PVP interactions (enhancing NP dispersion and diluting locally high NP
      concentration) but also increases the production rate by a factor of ca. 5.
      Further increase in the production rate can be achieved through parallelization
      of electrodes to construct comb electrodes. With respect to applications, carbon
      supported Pt NPs prepared by the new method exhibit catalytic activity and
      durability for methanol oxidation comparable or better than the commercial
      benchmark catalyst. A variety of Ag xAu100- x nanoalloys are characterized by
      ultraviolet-visible absorption spectroscopy and high-resolution transmission
      electron microscopy. The protocol for NP synthesis by cathodic corrosion should
      be a step toward its further use in academic research as well as in its practical
      upscaling.

PMID- 29446913
TI  - Optically Active 1D MoS2 Nanobelts.
AB  - Transition metal dichalcogenides can be synthesized in a wide range of
      structures. 1D geometries, including nanotubes and nanowires, are especially
      intriguing due to enhanced light-matter interactions stemming from both the
      thickness and width possessing subwavelength dimensions. In this letter, we
      demonstrate the synthesis of 1D MoS2 nanobelts through chemical vapor deposition
      and examine the mechanism driving the formation of this material. We also report
      enhanced light scattering within these structures. Finally, we investigate the
      phototransistor behavior of MoS2 nanobelts and observed a photoresponsivity
      around 1.5 A/W, an order of magnitude greater than analogous multilayer 2D MoS2
      sheets reported previously.

PMID- 29446914
TI  - Simultaneous Detection of Human C-Terminal p53 Isoforms by Single Template
      Molecularly Imprinted Polymers (MIPs) Coupled with Liquid Chromatography-Tandem
      Mass Spectrometry (LC-MS/MS)-Based Targeted Proteomics.
AB  - Abnormal expression of C-terminal p53 isoforms alpha, beta, and gamma can cause
      the development of cancers including breast cancer. To date, much evidence has
      demonstrated that these isoforms can differentially regulate target genes and
      modulate their expression. Thus, quantification of individual isoforms may help
      to link clinical outcome to p53 status and to improve cancer patient treatment.
      However, there are few studies on accurate determination of p53 isoforms,
      probably due to sequence homology of these isoforms and also their low abundance.
      In this study, a targeted proteomics assay combining molecularly imprinted
      polymers (MIPs) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was
      developed for simultaneous quantification of C-terminal p53 isoforms. Isoform
      specific surrogate peptides (i.e., KPLDGEYFTLQIR (peptide-alpha) for isoform
      alpha, KPLDGEYFTLQDQTSFQK (peptide-beta) for isoform beta, and KPLDGEYFTLQMLLDLR
      (peptide-gamma) for isoform gamma) were first selected and used in both MIPs
      enrichment and mass spectrometric detection. The common sequence KPLDGEYFTLQ of
      these three surrogate peptides was used as single template in MIPs. In addition
      to optimization of imprinting conditions and characterization of the prepared
      MIPs, binding affinity and cross-reactivity of the MIPs for each surrogate
      peptide were also evaluated. As a result, a LOQ of 5 nM was achieved, which was
      >15-fold more sensitive than that without MIPs. Finally, the assay was validated
      and applied to simultaneous quantitative analysis of C-terminal p53 isoforms
      alpha, beta, and gamma in several human breast cell lines (i.e., MCF-10A normal
      cells, MCF-7 and MDA-MB-231 cancer cells, and drug-resistant MCF-7/ADR cancer
      cells). This study is among the first to employ single template MIPs and cross
      reactivity phenomenon to select isoform-specific surrogate peptides and enable
      simultaneous quantification of protein isoforms in LC-MS/MS-based targeted
      proteomics.

PMID- 29446915
TI  - Radially Aligned Hierarchical Nickel/Nickel-Iron (Oxy)hydroxide Nanotubes for
      Efficient Electrocatalytic Water Splitting.
AB  - Designing well-controlled hierarchical structures on micrometer and nanometer
      scales represents one of the most important approaches for upgrading the
      catalytic abilities of electrocatalysts. Although NiFe (oxy)hydroxide has been
      widely studied as a water oxidation catalyst due to its high catalytic capability
      and abundance, its structural manipulation has been greatly restricted due to its
      inherent crystallographic stacking feature. In this work, we report for the first
      time the construction of a nanotube structure of NiFe (oxy)hydroxide with an
      inner Ni-rich layer, which was radially aligned on a macroporous nickel foam.
      Such a hierarchically structured material realized several crucial factors that
      are essential for excellent catalytic behaviors, including abundant catalytic
      sites, a high surface area, efficient ionic and electronic transport, etc., and
      the designed catalyst exhibited competitive electrocatalytic activity for
      reaction of not only oxygen evolution but also hydrogen evolution, which is very
      rare. As a result, this novel material was well-suited for the use as a
      bifunctional catalyst in an integrated water-splitting electrolyzer, which could
      be even driven by a single AA battery or a 1.5 V solar cell, outperforming a
      benchmark catalyst of noble-metal ruthenium-platinum combinations and most state
      of-the-art electrocatalysts. The work provided important suggestions for the
      rational modulation of catalysts with new structures targeted for high
      performance electrodes used in electrochemical applications.

PMID- 29446916
TI  - A Smart DNA Tweezer for Detection of Human Telomerase Activity.
AB  - Reliable and accurate detection of telomerase activity is crucial to better
      understand its role in cancer cells and to further explore its function in cancer
      diagnosis and treatment. Here, we construct a smart DNA tweezer (DT) for
      detection of telomerase activity. The DT is assembled by three specially designed
      single-stranded oligonucleotides: a central strand dually labeled with
      donor/acceptor fluorophores and two arm strands containing overhangs
      complementary to telomerase reaction products (TRPs). It can get closed through
      hybridization with TRPs and get reopen through strand displacement reaction by
      TRPs' complementary sequences. First, under the action of telomerase, telomerase
      binding substrates (TS) are elongated to generate TRPs ended with telomeric
      repeats (TTAGGG) n. TRPs hybridize with the two arm overhangs cooperatively and
      strain DT to closed state, inducing an increased fluorescence resonance energy
      transfer (FRET) efficiency, which is utilized for telomerase activity detection.
      Second, upon introduction of a removal strand (RS) complementary to TRPs, the
      closed DT is relaxed to open state via the toehold-mediated strand displacement,
      inducing a decreased FRET efficiency, which is utilized for determination of TRP
      length distribution. The detection limit of telomerase activity is equivalent to
      141 cells/MUL for HeLa cells, and telomerase-active cellular extracts can be
      differentiated from telomerase-inactive cellular extracts. Furthermore, TRPs
      owning 1, 2, 3, 4, and >=5 telomeric repeats are identified to account for 25.6%,
      20.5%, 15.7%, 12.5%, and 25.7%, respectively. The proposed strategy will offer a
      new approach for reliable, accurate detection of telomerase activity and product
      length distribution for deeper studying its role and function in cancer.

PMID- 29446917
TI  - Mapping the mAb Aggregation Propensity Using Self-Interaction Chromatography as a
      Screening Tool.
AB  - The osmotic second virial coefficient ( B2), which describes protein-protein
      molecular interactions in solution, was determined using self-interaction
      chromatography (SIC) for an IgG1-type mAb across a wide range of solution
      conditions. These data were compared with its time dependent aggregation
      behavior, as determined using size-exclusion chromatography (SEC), and its
      temperature dependent aggregation behavior using dynamic light scattering (DLS)
      over a four-week period (SEC) or overnight (DLS). DLS and SEC gave consistent
      data on aggregation behavior, which correlated well with experimental B2 trends
      across the wide pH (4-9) and NaCl concentration (0-1.0 M) ranges studied. The IgG
      aggregated at pH 4 for 0.5-1.0 M NaCl concentrations and for 0 M NaCl
      concentrations at pH 8. Best stability against aggregation was exhibited for the
      pH range from 5 to 8 at 0.8-1.0 M NaCl. SIC data were able to be classified
      within the one-day solution conditions for aggregation, which were not identified
      for 2-3 weeks in the accelerated SEC stability study. The ability of SIC to
      provide such data rapidly reflects the fundamentally thermodynamic nature of this
      parameter and of the aggregation process itself. Proteins with attractive protein
      protein interactions and negative B2 coefficients in the range -3 to -6 clearly
      exhibit aggregation behavior, while B2 values in the range 0 to 2 showed good
      stability toward aggregation. SIC allows the rapid screening of solution
      conditions for which mAbs will exhibit stability to aggregation while requiring
      90% less time and material compared with that required for a conventional SEC
      aggregation study.

PMID- 29446919
TI  - Evolution of NiO Island Size Distributions during the Oxidation of a Ni-5Cr
      Alloy: Experiment and Modeling.
AB  - The classic models of metal oxidation developed by Wagner and Cabrera and Mott
      presuppose the existence of a planar oxide film and develop expressions for the
      rate at which the film thickens. Missing from those models is a description of
      how that initially planar film forms. Using scanning tunneling microscopy, we
      study the growth of NiO islands on the (100) surface of a Ni-5Cr alloy during the
      oxidation regime where the initial planar film is formed as oxide islands. The
      island height and area distributions as a function of the oxygen exposure in
      Langmuir (1 L = 10-6 Torr s) are measured. Lateral island growth and thickening
      occur as seemingly separate processes, and after a critical thickness of ~0.4 nm
      is achieved, growth is purely in the lateral direction. We develop a surface
      diffusion model for the evolution of the island size distribution that accounts
      for the lateral growth and coalescence of the NiO islands. Our results indicate
      that the oxygen surface diffusion screening length [Formula: see text] controls
      the island evolution. The screening length is found to be 0.3-0.4 nm, which
      suggests that the processes leading to island growth are highly localized to the
      island edge.

PMID- 29446918
TI  - Three- and Two-Photon NIR-to-Vis (Yb,Er) Upconversion from ALD/MLD-Fabricated
      Molecular Hybrid Thin Films.
AB  - We report blue, green, and red upconversion emissions with strongly angular
      dependent intensities for a new type of hybrid (Y,Yb,Er)-pyrazine thin films
      realized using the atomic/molecular layer deposition thin-film fabrication
      technology. The luminescence emissions in our amorphous (Y,Yb,Er)-pyrazine thin
      films of a controllable nanothickness originate from three- and two-photon NIR-to
      vis excitation processes. In addition to shielding the lanthanide ions from
      nonradiative de-excitation, the network of interconnected organic molecules
      serves as an excellent matrix for the Yb3+-to-Er3+ excitation energy transfer.
      This suggests a new approach to achieve efficient upconverting molecular
      materials with the potential to be used for next-generation medical diagnostics,
      waveguides, and surface-sensitive detectors.

PMID- 29446920
TI  - Homogeneous Noncompetitive Luminescent Immunodetection of Small Molecules by
      Ternary Protein Fragment Complementation.
AB  - The homogeneous immunological detection of small molecules at high sensitivity is
      still a daunting task. Here, we tried sensitive noncompetitive detection of small
      peptides based on the open-sandwich immunoassay principle, which was combined
      with a bioluminescent protein-fragment complementation assay (PCA) in vitro.
      Since the detection of antigen-induced approximation of the two antibody variable
      region fragments VH and VL by the standard Nanoluc-based PCA utilizing larger
      (LgBiT) and shorter (SmBiT) fragments was not successful, we decided to further
      split LgBiT into two, yielding smaller N-terminal derivative (LnBiT) and two C
      terminal, 11 residue peptides (LcBiT and SmBiT) corresponding to consecutive beta
      strands, to which VH and VL were each fused and expressed in Escherichia coli
      cells. Through the optimization of reaction conditions and peptide sequence, the
      antigen osteocalcin peptide can be noncompetitively detected with a low
      background signal and limit of detection, yielding a high light emission of 88%
      compared to that of the wild-type enzyme. Since the luminescence of this open
      sandwich bioluminescent immunoassay (OS-BLIA) can be observed with the naked eye,
      it could become the foundation of many point-of-care detection systems.

PMID- 29446921
TI  - Modeling of Pharmaceutical Biotransformation by Enriched Nitrifying Culture under
      Different Metabolic Conditions.
AB  - Pharmaceutical removal could be significantly enhanced through cometabolism
      during nitrification processes. To date, pharmaceutical biotransformation models
      have not considered the formation of transformation products associated with the
      metabolic type of microorganisms. Here we report a comprehensive model to
      describe and evaluate the biodegradation of pharmaceuticals and the formation of
      their biotransformation products by enriched nitrifying cultures. The
      biotransformation of parent compounds was linked to the microbial processes via
      cometabolism induced by ammonium-oxidizing bacteria (AOB) growth, metabolism by
      AOB, cometabolism by heterotrophs (HET) growth, and metabolism by HET in the
      model framework. The model was calibrated and validated using experimental data
      from pharmaceutical biodegradation experiments at realistic levels, taking two
      pharmaceuticals as examples, i.e., atenolol and acyclovir. Results demonstrated
      the good predictive performance of the established biotransformation model under
      different metabolic conditions, as well as the reliability of the established
      model in predicting different pharmaceutical biotransformations. The linear
      positive correlation between ammonia oxidation rate and pharmaceutical
      degradation rate confirmed the major role of cometabolism induced by AOB in the
      pharmaceutical removal. Dissolved oxygen was also revealed to be capable of
      regulating the pharmaceutical biotransformation cometabolically, and the
      substrate competition between ammonium and pharmaceuticals existed especially at
      high ammonium concentrations.

PMID- 29446923
TI  - Ligand-Controlled Regioselective Hydrocarboxylation of Styrenes with CO2 by
      Combining Visible Light and Nickel Catalysis.
AB  - The ligand-controlled Markovnikov and anti-Markovnikov hydrocarboxylation of
      styrenes with atmospheric pressure of CO2 at room temperature using dual visible
      light-nickel catalysis has been developed. In the presence of neocuproine as
      ligand, the Markovnikov product is obtained exclusively, while employing 1,4
      bis(diphenylphosphino)butane (dppb) as the ligand favors the formation of the
      anti-Markovnikov product. A range of functional groups and electron-poor, 
      neutral, as well as electron-rich styrene derivatives are tolerated by the
      reaction, providing the desired products in moderate to good yields. Preliminary
      mechanistic investigations indicate the generation of a nickel hydride (H-NiII)
      intermediate, which subsequently adds irreversibly to styrenes.

PMID- 29446922
TI  - Enantioselective Intermolecular Pd-Catalyzed Hydroalkylation of Acyclic 1,3
      Dienes with Activated Pronucleophiles.
AB  - We report a highly enantioselective Pd-PHOX-catalyzed intermolecular
      hydroalkylation of acyclic 1,3-dienes. Meldrum's acid derivatives and other
      activated C-pronucleophiles, such as beta-diketones and malononitriles, react
      with a variety of aryl- and alkyl-substituted dienes in <=20 h at room
      temperature. The coupled products, obtained in up to 96% yield and 97.5:2.5 er,
      are easily transformed into useful chemical building blocks for downstream
      synthesis.

PMID- 29446924
TI  - Advances in Electroanalytical Chemistry.

PMID- 29446925
TI  - Visible-Light-Driven Photosystems Using Heteroleptic Cu(I) Photosensitizers and
      Rh(III) Catalysts To Produce H2.
AB  - The synthesis of two new heteroleptic Cu(I) photosensitizers (PS),
      [Cu(Xantphos)(NN)]PF6 (NN = biq = 2,2'-biquinoline, dmebiq = 2,2'-biquinoline
      4,4'-dimethyl ester; Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene),
      along with the associated structural, photophysical, and electrochemical
      properties, are described. The biquinoline diimine ligand extends the PS light
      absorbing properties into the visible with a maximum absorption at 455 and 505 nm
      for NN = biq and dmebiq, respectively, in CH2Cl2 solvent. Following
      photoexcitation, both Cu(I) PS are emissive at low energy, albeit displaying
      stark differences in their excited state lifetimes (tauMLCT = 410 +/- 5 (biq) and
      44 +/- 4 ns (dmebiq)). Cyclic voltammetry indicates a Cu-based HOMO and NN-based
      LUMO for both complexes, whereby the methyl ester substituents stabilize the LUMO
      within [Cu(Xantphos)(dmebiq)]+ by ~0.37 V compared to the unsubstituted analogue.
      When combined with H2O, N,N-dimethylaniline (DMA) electron donor, and cis
      [Rh(NN)2Cl2]PF6 (NN = Me2bpy = 4,4'-dimethyl-2,2'-bipyridine, bpy = 2,2'
      bipyridine, dmebpy = 2,2'-bipyridine-4,4'-dimethyl ester) water reduction
      catalysts (WRC), photocatalytic H2 evolution is only observed using the
      [Cu(Xantphos)(biq)]+ PS. Furthermore, the choice of cis-[Rh(NN)2Cl2]+ WRC
      strongly affects the catalytic activity with turnover numbers (TONRh = mol H2 per
      mol Rh catalyst) of 25 +/- 3, 22 +/- 1, and 43 +/- 3 for NN = Me2bpy, bpy, and
      dmebpy, respectively. This work illustrates how ligand modification to carefully
      tune the PS light absorbing, excited state, and redox-active properties, along
      with the WRC redox potentials, can have a profound impact on the photoinduced
      intermolecular electron transfer between components and the subsequent catalytic
      activity.

PMID- 29446926
TI  - Structural Diversity of Coordination Polymers Based on a Heterotopic Ligand:
      Cu(II)-Carboxylate vs Cu(I)-Thiolate.
AB  - Two copper(II)-carboxylate disulfide coordination polymers
      [Cu2((O2CPhS)2)2(H2O)2] n (1, 2) and one copper(I)-thiolate coordination polymer
      [Cu( p-SPhCO2H)] n (3) have been synthesized using either the 4-mercaptobenzoic
      acid (HSPhCO2H) or the 4,4'-dithiodibenzoic acid ((SPhCO2H)2) as ligand. These
      three compounds were characterized by X-ray diffraction, IR, and
      thermogravimetric analyses. Compounds 1 and 2 are polymorphs with the presence,
      for both, of dinuclear paddle-wheel copper(II)-carboxylates. In 1, the adjacent
      dimeric Cu2 units are linked by two (O2CPhS)2 ligands generating a cyclic loop
      chain, and in 2, each pair of Cu (II) atoms is linked by four ligands to create
      2D networks, that are 2-fold interpenetrated. Compound 3 presents a lamellar
      structure, with an exceptional thermal and chemical stability, and exhibits
      intrinsic multiple emission between 485 and 660 nm. The different intensities of
      these bands generate a cyclic luminescence thermochromism from yellow to green to
      yellow.

PMID- 29446927
TI  - Gasoline Particulate Filters as an Effective Tool to Reduce Particulate and
      Polycyclic Aromatic Hydrocarbon Emissions from Gasoline Direct Injection (GDI)
      Vehicles: A Case Study with Two GDI Vehicles.
AB  - We assessed the gaseous, particulate, and genotoxic pollutants from two current
      technology gasoline direct injection vehicles when tested in their original
      configuration and with a catalyzed gasoline particulate filter (GPF). Testing was
      conducted over the LA92 and US06 Supplemental Federal Test Procedure (US06)
      driving cycles on typical California E10 fuel. The use of a GPF did not show any
      fuel economy and carbon dioxide (CO2) emission penalties, while the emissions of
      total hydrocarbons (THC), carbon monoxide (CO), and nitrogen oxides (NOx) were
      generally reduced. Our results showed dramatic reductions in particulate matter
      (PM) mass, black carbon, and total and solid particle number emissions with the
      use of GPFs for both vehicles over the LA92 and US06 cycles. Particle size
      distributions were primarily bimodal in nature, with accumulation mode particles
      dominating the distribution profile and their concentrations being higher during
      the cold-start period of the cycle. Polycyclic aromatic hydrocarbons (PAHs) and
      nitrated PAHs were quantified in both the vapor and particle phases of the PM,
      with the GPF-equipped vehicles practically eliminating most of these species in
      the exhaust. For the stock vehicles, 2-3 ring compounds and heavier 5-6 ring
      compounds were observed in the PM, whereas the vapor phase was dominated mostly
      by 2-3 ring aromatic compounds.

PMID- 29446928
TI  - Comprehensive Mechanistic Insight into Cooperative Lewis Acid/Cp*CoIII-Catalyzed
      C-H/N-H Activation for the Synthesis of Isoquinolin-3-ones.
AB  - The mechanism of B(C6F5)3 promoted Cp*CoIII-catalyzed C-H functionalization was
      investigated in detail employing density functional theory (DFT). The formation
      free energy of every possible species in the multicomponent complex system was
      explored and the optimal active catalyst was screened out. The results uncover
      the role of B(C6F5)3 played in forming active catalyst is from the coordination
      with OAc-, but not from the formation of [I(C6F5)3B]-, and no acceleration effect
      is found in C-H activation as well as the formation of CoIII-carbene
      intermediate. Moreover, present theoretical results elucidate the Cp*CoIII
      catalyzed C-H activation is mediated by imine N-coordination other than general
      proposed the sequence of N-deprotonation directed C-H activation. The metal
      controlled C-H/N-H selectivity was then elucidated by insighting into
      [Cp*CoIIIOAc]+/[Cp*RhIIIOAc]+-catalyzed C-H and N-H activations, respectively.

PMID- 29446929
TI  - Enhanced Reactivity and Electron Selectivity of Sulfidated Zerovalent Iron toward
      Chromate under Aerobic Conditions.
AB  - When zerovalent iron (ZVI) is used in reductive removal of contaminants from
      industrial wastewater, where dissolved oxygen (DO) competes with target
      contaminant for the electrons donated by ZVI, both the reactivity and the
      electron selectivity (ES) of ZVI toward target contaminant are critical. Thus,
      the reactivity and ES of two sulfidated ZVI (S-ZVI) samples, synthesized by ball
      milling with elemental sulfur (S-ZVIbm) and reacting with Na2S (S-ZVINa2S),
      toward Cr(VI) under aerobic conditions were investigated. Sulfidation appreciably
      increased the reactivity of ZVI and the ratio of the rate constants for Cr(VI)
      removal by S-ZVIbm or S-ZVINa2S to their counterparts without sulfur fell in the
      range of 1.4-29.9. ES of S-ZVIbm and S-ZVINa2S toward Cr(VI) were determined to
      be 14.6% and 13.3%, which were 10.7- and 7.5-fold greater than that without
      sulfidation, respectively. This was mainly ascribed to the greater improving
      effect of sulfidation on the reduction rate of Cr(VI) than that of DO by ZVI. The
      improving effects of sulfidation on the performance of ZVI were mainly due to the
      following mechanisms: sulfidation increased the specific surface area of ZVI, the
      FeS x layer facilitated the enrichment of Cr(VI) anions on S-ZVI surface because
      of its anions selective property and favored the electron transfer from Fe0 core
      to Cr(VI) at the surface because of its role as efficient electron conductor.

PMID- 29446930
TI  - Spectroscopic and Structural Characterization of Mn(III)-Alkylperoxo Complexes
      Supported by Pentadentate Amide-Containing Ligands.
AB  - Manganese-alkylperoxo species have been proposed as important intermediates in
      certain enzymatic pathways and are presumed to play a key role in catalytic
      substrate oxidation cycles involving manganese catalysts and peroxide oxidants.
      However, structural and spectroscopic understanding of these intermediates is
      very limited, with only one series of synthetic MnIII-alkylperoxo complexes
      having been reported. In the present study, we describe the formation and
      properties of two new MnIII-alkylperoxo complexes, namely, [MnIII(OO tBu)(dpaq)]+
      and [MnIII(OO tBu)(dpaq2Me)]+, which utilize the anionic, amide-containing
      pentadentate dpaq ligand platform. These complexes were generated by reacting the
      corresponding MnII precursors with a large excess of tBuOOH at -15  degrees C in
      MeCN. In both cases, the corresponding mononuclear MnIII-hydroxo complexes
      [MnIII(OH)(dpaq)]+ and [MnIII(OH)(dpaq2Me)]+ are observed as intermediates en
      route to the MnIII-alkylperoxo adducts. These new MnIII-alkylperoxo complexes
      were characterized by electronic absorption, infrared, and Mn K-edge X-ray
      absorption spectroscopies. Complementary density functional theory calculations
      were also performed to gain insight into their bonding and structural properties.
      Compared to previously reported MnIII-alkylperoxo adducts, the MnIII centers in
      these complexes exhibit significantly altered primary coordination spheres, with
      a strongly donating anionic amide nitrogen located trans to the alkylperoxo
      moiety. This results in MnIII-alkylperoxo bonding that is dominated by sigma
      interactions between the alkylperoxo piip*(O-O) orbital and the Mn d z2 orbital.

PMID- 29446931
TI  - Reactivity of Two-Electron-Reduced Boron Formazanate Compounds with
      Electrophiles: Facile N-H/N-C Bond Homolysis Due to the Formation of Stable
      Ligand Radicals.
AB  - The reactivity of a boron complex with a redox-active formazanate ligand, LBPh2
      [L = PhNNC( p-tol)NNPh], was studied. Two-electron reduction of this main-group
      complex generates the stable, nucleophilic dianion [LBPh2]2-, which reacts with
      the electrophiles BnBr and H2O to form products that derive from ligand
      benzylation and protonation, respectively. The resulting complexes are anionic
      boron analogues of leucoverdazyls. N-C and N-H bond homolysis of these compounds
      was studied by exchange NMR spectroscopy and kinetic experiments. The weak N-C
      and N-H bonds in these systems derive from the stability of the resulting
      borataverdazyl radical, in which the unpaired electron is delocalized over the
      four N atoms in the ligand backbone. We thus demonstrate the ability of this
      system to take up two electrons and an electrophile (E+ = Bn+, H+) in a process
      that takes place on the organic ligand. In addition, we show that the [2e-/E+]
      stored on the ligand can be converted to E* radicals, reactivity that has
      implications in energy storage applications such as hydrogen evolution.

PMID- 29446932
TI  - Separation of Xylene Isomers through Multiple Metal Site Interactions in Metal
      Organic Frameworks.
AB  - Purification of the C8 alkylaromatics o-xylene, m-xylene, p-xylene, and
      ethylbenzene remains among the most challenging industrial separations, due to
      the similar shapes, boiling points, and polarities of these molecules. Herein, we
      report the evaluation of the metal-organic frameworks Co2(dobdc) (dobdc4- = 2,5
      dioxido-1,4-benzenedicarboxylate) and Co2( m-dobdc) ( m-dobdc4- = 4,6-dioxido-1,3
      benzenedicarboxylate) for the separation of xylene isomers using single-component
      adsorption isotherms and multicomponent breakthrough measurements. Remarkably,
      Co2(dobdc) distinguishes among all four molecules, with binding affinities that
      follow the trend o-xylene > ethylbenzene > m-xylene > p-xylene. Multicomponent
      liquid-phase adsorption measurements further demonstrate that Co2(dobdc)
      maintains this selectivity over a wide range of concentrations. Structural
      characterization by single-crystal X-ray diffraction reveals that both frameworks
      facilitate the separation through the extent of interaction between each C8 guest
      molecule with two adjacent cobalt(II) centers, as well as the ability of each
      isomer to pack within the framework pores. Moreover, counter to the presumed
      rigidity of the M2(dobdc) structure, Co2(dobdc) exhibits an unexpected structural
      distortion in the presence of either o-xylene or ethylbenzene that enables the
      accommodation of additional guest molecules.

PMID- 29446933
TI  - Dietary Sodium Butyrate Supplementation Reduces High-Concentrate Diet Feeding
      Induced Apoptosis in Mammary Cells in Dairy Goats.
AB  - Eighteen lactating goats (38.86 +/- 2.06 kg) were randomly allocated to three
      groups. One group was fed a low-concentrate (LC) diet (forage:concentrate = 6:4),
      while the other two groups were fed a high-concentrate (HC) diet
      (forage:concentrate = 4:6) or an HC diet supplemented with sodium butyrate (BHC)
      for 20 weeks. Samples of ruminal fluid, milk, hepatic blood plasma, and mammary
      gland tissue were prepared for the experimental analysis. The lipopolysaccharide
      (LPS) concentration, caspase-3 and -8 enzymatic activity, caspase-3 and -8 mRNA
      expression, and NF-kappaB (p65), phosphorylated-p65, bax, cytochrome c, and
      caspase-3 protein expression were higher in the HC group than those in the LC
      group; however, the levels of these parameters were lower in the BHC group than
      those in the HC group. Moreover, bcl-2 mRNA and protein expression was higher in
      the BHC group than that in the HC or LC groups, and no significant difference was
      observed between the HC and LC groups. Thus, feeding lactating goats an HC diet
      induces apoptosis in mammary cells, and supplementing the diet with sodium
      butyrate reduces the concentrations of LPS and proinflammatory cytokines,
      subsequently attenuating the activation of NF-kappaB and caspase-3 and eventually
      inhibiting apoptosis in mammary cells.

PMID- 29446935
TI  - Amine-Functionalized Al-MOF#@ yxSm2O3-ZnO: A Visible Light-Driven Nanocomposite
      with Excellent Photocatalytic Activity for the Photo-Degradation of Amoxicillin.
AB  - A visible light-driven amine-functionalized Al-based MOF#@ yxSm2O3-ZnO
      nanocomposite (NH2-MOF#@ yxSm2O3-ZnO NCP) was synthesized as an effective
      photocatalyst for AMX degradation in the presence of ultrasound, in which # is
      MOF synthesis conditions from MOFI to MOFXII and x and y stand for the weight
      percentages of Sm2O3-to-ZnO and Sm2O3-ZnO-to-MOF, respectively. The beta-lactam
      antibiotic AMX, which is widely used for treating Gram-positive and Gram-negative
      bacterial infections in both animals and humans, was employed as a model
      pollutant. Using different detection techniques, the synthesized materials were
      characterized. Furthermore, effects of different synthesis methods, ultrasonic
      time, precursor concentration, sonication amplitude, and modulators on the MOFs
      photocatalytic behavior were taken into account. Also, catalytic dose and
      recycling, H2O2 usage, and operating pH effects were investigated. Compared to
      the pure forms of NH2-MOF-53(Al) and Sm2O3-ZnO, the NCPs having the optimal Sm2O3
      ZnO and NH2-MOF-53(Al) contents highly influenced the photocatalytic activity due
      to the synergetic impacts of the high charge mobility and the red shift in the
      NH2-MOF@Sm2O3-ZnO NCPs absorption edge compared to the Sm2O3-ZnO nanoflowers. We
      used a TOC analyzer, UV/vis spectroscopy, and HPLC chromatogram to estimate the
      rate of AMX elimination in water over NH2-MOFXII@307Sm2O3-ZnO NCPs as our optimal
      sample. In addition, after the AMX pollutant degradation, the NH2-MOF@Sm2O3-ZnO
      NCPs were structurally stable and maintained the majority of their photocatalytic
      properties even after five runs of recycling process The NH2-MOFXII@307Sm2O3-ZnO
      NCPs as the superior photocatalysts were more examined and a mechanism for the
      AMX degradation was suggested. As a suggestion, our obtained results can be used
      as a starting point for the preparation of the other heterogeneous MOF-based NCPs
      combined with the Sm2O3-ZnO for a variety of applications such as the
      environmental remediation.

PMID- 29446934
TI  - Guanidinium-Functionalized Interpolyelectrolyte Complexes Enabling RNAi in
      Resistant Insect Pests.
AB  - RNAi-based technologies are ideal for pest control as they can provide species
      specificity and spare nontarget organisms. However, in some pests biological
      barriers prevent use of RNAi, and therefore broad application. In this study we
      tested the ability of a synthetic cationic polymer, poly-[ N-(3
      guanidinopropyl)methacrylamide] (pGPMA), that mimics arginine-rich cell
      penetrating peptides to trigger RNAi in an insensitive animal- Spodoptera
      frugiperda. Polymer-dsRNA interpolyelectrolyte complexes (IPECs) were found to be
      efficiently taken up by cells, and to drive highly efficient gene knockdown.
      These IPECs could also trigger target gene knockdown and moderate larval
      mortality when fed to S. frugiperda larvae. This effect was sequence specific,
      which is consistent with the low toxicity we found to be associated with this
      polymer. A method for oral delivery of dsRNA is critical to development of RNAi
      based insecticides. Thus, this technology has the potential to make RNAi-based
      pest control useful for targeting numerous species and facilitate use of RNAi in
      pest management practices.

PMID- 29446936
TI  - Will We Always Have Paris? CO2 Reduction without the Clean Power Plan.

PMID- 29446937
TI  - Preparation, Structure Evolution, and Metal-Insulator Transition of Na xRhO2
      Crystals (0.25 <= x <= 1).
AB  - The triangular lattice Na xRhO2 contains a 4d Rh element with large spin-orbit
      coupling, and the electron-electron correlation effect is expected to have some
      novel physical properties. Here we report NaRhO2 crystal growth by Na2CO3 vapor
      growth and a series of Na xRhO2 (0.25 <= x <= 1) crystals prepared using the
      chemical desodiation method. Na xRhO2 reveals a layer structure with the space
      group R3 m, and the lattice parameter a evolves from 3.09 to 3.03 A and c from
      15.54 to 15.62 A when x decreases from 1.0 to 0.2. Decreasing potassium
      concentration leads to a contraction of the RhO6 octahedral layers, which may be
      attributed to a higher covalency of Rh-O bonds. More important, the metal
      insulator transition in Na xRhO2 was observed in resistivity along the ab plane.
      The conducting mechanism of Na xRhO2 is strongly dependent on x. Two-dimensional
      variable range hopping (VRH) mechanisms (0.67 <= x <= 1) and metallic behaviors
      (0.42 and 0.47) are observed in temperature-dependent resistivity. The origin of
      this metal-insulator transition was discussed on the basis of the Ioffe-Regel
      criterion. Our work demonstrates the strong correlation between sodium
      concentration and physical properties of Na xRhO2.

PMID- 29446938
TI  - Hypoglycemic Effects of Pyrodextrins with Different Molecular Weights and
      Digestibilities in Mice with Diet-Induced Obesity.
AB  - Pyrodextrin shares some properties of resistant starch, which is metabolically
      beneficial, and has potential applications as a functional food. In this study,
      we report that the oral administration of pyrodextrin (50 mg/kg/d for 7 weeks)
      decreased blood glucose (from 9.18 +/- 1.47 to 7.67 +/- 0.42 mmol/L), serum
      HbA1c, triglycerides, adipocyte size, and body weight (from 24.4 +/- 1.2 to 22.5
      +/- 1.2 g) in mice with high-fat-diet-induced obesity. Western-blotting analysis
      suggested that pyrodextrins decreased intestinal SGLT-1 and GLUT-2 expression to
      ~70 and ~60% of the obese control, respectively, which slowed down glucose
      transportation from the gut into the blood and tentatively improved hepatic
      metabolism. Moreover, the pyrodextrin with a lower molecular weight of 44 kDa, a
      more branched structure, and increased nondigestible starch of 46.2 +/- 0.3%
      showed stronger hypoglycemic activity. This work provides important information
      for developing pyrodextrins as a functional food and dietary supplement for the
      management of obesity and diabetes.

PMID- 29446939
TI  - Particle/Gas Partitioning of Phthalates to Organic and Inorganic Airborne
      Particles in the Indoor Environment.
AB  - The particle/gas partition coefficient Kp is an important parameter affecting the
      fate and transport of indoor semivolatile organic compounds (SVOCs) and resulting
      human exposure. Unfortunately, experimental measurements of Kp exist almost
      exclusively for atmospheric polycyclic aromatic hydrocarbons, with very few
      studies focusing on SVOCs that occur in indoor environments. A specially designed
      tube chamber operating in the laminar flow regime was developed to measure Kp of
      the plasticizer di-2-ethylhexyl phthalate (DEHP) for one inorganic (ammonium
      sulfate) and two organic (oleic acid and squalane) particles. The values of Kp
      for the organic particles (0.23 +/- 0.13 m3/MUg for oleic acid and 0.11 +/- 0.10
      m3/MUg for squalane) are an order of magnitude higher than those for the
      inorganic particles (0.011 +/- 0.004 m3/MUg), suggesting that the process by
      which the particles accumulate SVOCs is different. A mechanistic model based on
      the experimental design reveals that the presence of the particles increases the
      gas-phase concentration gradient in the boundary layer, resulting in enhanced
      mass transfer from the emission source into the air. This novel approach provides
      new insight into experimental designs for rapid Kp measurement and a sound basis
      for investigating particle-mediated mass transfer of SVOCs.

PMID- 29446940
TI  - Ru(II) Compounds: Next-Generation Anticancer Metallotherapeutics?
AB  - Metal based therapeutics are a precious class of drugs in oncology research that
      include examples of theranostic drugs, which are active in both diagnostic,
      specifically imaging, and therapeutics applications. Ruthenium compounds have
      shown selective bioactivity and the ability to overcome the resistance that
      platinum-based therapeutics face, making them effective oncotherapeutic
      competitors in rational drug invention approaches. The development of
      antineoplastic ruthenium therapeutics is of particular interest because ruthenium
      containing complexes NAMI-A, KP1019, and KP1339 entered clinical trials and DW1/2
      is in preclinical levels. The very robust, conformationally rigid organometallic
      Ru(II) compound DW1/2 is a protein kinase inhibitor and presents new Ru(II)
      compound designs as anticancer agents. Over the recent years, numerous strategies
      have been used to encapsulate Ru(II) derived compounds in a nanomaterial system,
      improving their targeting and delivery into neoplastic cells. A new photodynamic
      therapy based Ru(II) therapeutic, TLD-1433, has also entered clinical trials.
      Ru(II)-based compounds can also be photosensitizers for photodynamic therapy,
      which has proven to be an effective new, alternative, and noninvasive oncotherapy
      modality.

PMID- 29446941
TI  - Ni-Catalyzed Regioselective Dicarbofunctionalization of Unactivated Olefins by
      Tandem Cyclization/Cross-Coupling and Application to the Concise Synthesis of
      Lignan Natural Products.
AB  - We disclose a (terpy)NiBr2-catalyzed reaction protocol that regioselectively
      difunctionalizes unactivated olefins with tethered alkyl halides and arylzinc
      reagents. The reaction shows an excellent functional group tolerance (such as
      ketones, esters, nitriles, and halides) and a moderate to good level of
      diastereoselectivity. The current cyclization/cross-coupling also tolerates
      molecules containing base-sensitive racemizable stereocenters, which are
      preserved without racemization during the reaction. This cyclization/cross
      coupling provides a rapid access to (arylmethyl)carbo- and heterocyclic
      scaffolds, which occur widely as structural cores in various natural products and
      bioactive molecules. In order to show synthetic utility and generality, we have
      applied this new method in gram-scale quantities to the concise synthesis of six
      lignan natural products containing three different structural frameworks. We
      further conducted mechanistic investigations with radical probes and selectivity
      studies, which indicated that the current reaction proceeds via a single electron
      transfer (SET) process.

PMID- 29446942
TI  - Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide
      Peroxisome Proliferator Activated Receptor (PPAR) alpha/gamma/delta Triple
      Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate.
AB  - Here, we describe the identification and synthesis of novel indole sulfonamide
      derivatives that activate the three peroxisome proliferator activated receptor
      (PPAR) isoforms. Starting with a PPARalpha activator, compound 4, identified
      during a high throughput screening (HTS) of our proprietary screening library, a
      systematic optimization led to the discovery of lanifibranor (IVA337) 5, a
      moderately potent and well balanced pan PPAR agonist with an excellent safety
      profile. In vitro and in vivo, compound 5 demonstrated strong activity in models
      that are relevant to nonalcoholic steatohepatitis (NASH) pathophysiology
      suggesting therapeutic potential for NASH patients.

PMID- 29446943
TI  - Fe2O3-Promoted Intermolecular Chlorotrifluoromethylthiolation of Alkenes.
AB  - A simple, convenient method for intermolecular chlorotrifluoromethylthiolation of
      alkenes by using a low-cost and more abundant iron catalyst has been developed.
      This protocol provides a straightforward way to synthesize a variety of useful
      SCF3-containing chlorides from a wide range of alkenes, including electron
      deficient, aromatic, and unactivated alkenes. Mechanistic studies indicate that
      this is a free radical transformation, and the stronger electrophilic
      trifluoromethylthiolating reagent CF3SCl was generated in situ under the employed
      conditions. The synthetic applications of this approach were also explored by a
      variety of synthetically useful transformations.

PMID- 29446944
TI  - Magnesium-Promoted Additions of Difluoroenolates to Unactivated Imines.
AB  - Although there are many synthetic methods to produce fluorinated and
      trifluoromethylated organic structures, the construction of difluoromethylated
      compounds remains a synthetic challenge. We have discovered that unactivated
      imines will react with difluoroenolates under exceedingly mild conditions when
      using magnesium salts and organic bases. We have applied this approach to the
      iminoaldol reaction to produce difluoromethylene groups as alpha,alpha-difluoro
      beta-amino-carbonyl groups. This method provides synthetically useful quantities
      of difficult to access alpha,alpha-difluoro-beta-aminoketones without the need of
      protecting groups or the use of activated imines. Moreover, we have applied this
      strategy to create analogues of the dual orexin receptor antagonist, almorexant,
      in only two synthetic steps.

PMID- 29446945
TI  - Statistical Model To Decipher Protein Folding/Unfolding at a Local Scale.
AB  - Protein folding/unfolding can be analyzed experimentally at a local scale by
      monitoring the physical properties of local probes as a function of the
      temperature, for example, the distance between fluorophores or the values of
      chemical shifts of backbone atoms. Here, the analytical Lifson-Roig model for the
      helix-coil transition is modified to analyze local thermal unfolding of the fast
      folder W protein of bacteriophage lambda (gpW) simulated by all-atom molecular
      dynamics (MD) simulations in explicit solvent at 15 different temperatures. The
      protein structure is described by the coarse-grained dihedral angles (gamma) and
      bond angles (theta) built between successive Calpha-Calpha virtual bonds. Each
      (gamma,theta) pair serves as a local probe of protein unfolding. Local native/non
      native states are defined for each pair of (gamma,theta) angles by analyzing the
      free-energy landscapes Delta G(gamma,theta) computed from MD trajectories. The
      three local elementary equilibrium constants of the model are extracted for each
      (gamma,theta) pair along the sequence from MD simulations, and the model
      predictions are compared to the MD data. Using only the local equilibrium
      constants as an input, we show that the local denaturation curves computed from
      the model partition function fit their MD simulated counterparts in a satisfying
      manner without any adjustment. In the model and MD simulations, gpW unfolds
      gradually between 320 and 340 K, with an average native percentage decreasing
      from 0.8 (320 K) to 0.2 (340 K). In the prism of the model, there is no stable
      structure at the local scale in this 20 K unfolding temperature range. The
      enthalpy change upon local unfolding computed from the model and from MD
      trajectories suggests that the unfolded state between 320 and 340 K corresponds
      to a dynamical equilibrium between a large ensemble of constantly changing
      structures. The present results confirm the downhill unfolding of gpW, which does
      not obey a two-state global folding/unfolding model, and shed light on the
      interpretation of local denaturation curves.

PMID- 29446946
TI  - Rapid Convergence of Energy and Free Energy Profiles with Quantum Mechanical Size
      in Quantum Mechanical-Molecular Mechanical Simulations of Proton Transfer in DNA.
AB  - In recent years, a number of quantum mechanical-molecular mechanical (QM/MM)
      enzyme studies have investigated the dependence of reaction energetics on the
      size of the QM region using energy and free energy calculations. In this study,
      we revisit the question of QM region size dependence in QM/MM simulations within
      the context of energy and free energy calculations using a proton transfer in a
      DNA base pair as a test case. In the simulations, the QM region was treated with
      a dispersion-corrected AM1/d-PhoT Hamiltonian, which was developed to accurately
      describe phosphoryl and proton transfer reactions, in conjunction with an
      electrostatic embedding scheme using the particle-mesh Ewald summation method.
      With this rigorous QM/MM potential, we performed rather extensive QM/MM sampling,
      and found that the free energy reaction profiles converge rapidly with respect to
      the QM region size within ca. +/-1 kcal/mol. This finding suggests that the
      strategy of QM/MM simulations with reasonably sized and selected QM regions,
      which has been employed for over four decades, is a valid approach for modeling
      complex biomolecular systems. We point to possible causes for the sensitivity of
      the energy and free energy calculations to the size of the QM region, and
      potential implications.

PMID- 29446947
TI  - "On Water'' Promoted Ullmann-Type C-N Bond-Forming Reactions: Application to
      Carbazole Alkaloids by Selective N-Arylation of Aminophenols.
AB  - The Ullmann-type cross coupling of a variety of aromatic, aliphatic amines with
      aryl halides is reported using a CuI-based catalytic system in combination with
      an easily accessible prolinamide ligand in aqueous media. The method is mild and
      tolerant to air, moisture, and a wide range of functional groups, providing a
      novel way to access a variety of aminated products. Secondary amines like
      heteroaromatic amines and nucleobases have also been used, affording the
      corresponding coupling products in good to excellent yields. Moreover, this
      method has been employed for chemoselective C-N arylation of aminophenols and
      further utilized for the synthesis of carbazole natural products, avoiding the
      protection and deprotection steps.

PMID- 29446948
TI  - A Structure-Activity Relationship Study of Bitopic N6-Substituted Adenosine
      Derivatives as Biased Adenosine A1 Receptor Agonists.
AB  - The adenosine A1 receptor (A1AR) is a potential novel therapeutic target for
      myocardial ischemia-reperfusion injury. However, to date, clinical translation of
      prototypical A1AR agonists has been hindered due to dose limiting adverse
      effects. Recently, we demonstrated that the biased bitopic agonist 1, consisting
      of an adenosine pharmacophore linked to an allosteric moiety, could stimulate
      cardioprotective A1AR signaling in the absence of unwanted bradycardia.
      Therefore, this study aimed to investigate the structure-activity relationship of
      compound 1 biased agonism. A series of novel derivatives of 1 were synthesized
      and pharmacologically profiled. Modifications were made to the orthosteric
      adenosine pharmacophore, linker, and allosteric 2-amino-3-benzoylthiophene
      pharmacophore to probe the structure-activity relationships, particularly in
      terms of biased signaling, as well as A1AR activity and subtype selectivity.
      Collectively, our findings demonstrate that the allosteric moiety, particularly
      the 4-(trifluoromethyl)phenyl substituent of the thiophene scaffold, is important
      in conferring bitopic ligand bias at the A1AR.

PMID- 29446949
TI  - Positive and Negative Allosteric Modulators of N-Methyl-d-aspartate (NMDA)
      Receptors: Structure-Activity Relationships and Mechanisms of Action.
AB  - Excitatory activity in the CNS is predominately mediated by l-glutamate through
      several families of l-glutamate neurotransmitter receptors. Of these, the N
      methyl-d-aspartate receptor (NMDAR) family has many critical roles in CNS
      function and in various neuropathological and psychiatric conditions. Until
      recently, the types of compounds available to regulate NMDAR function have been
      quite limited in terms of mechanism of action, subtype selectivity, and
      biological effect. However, several new classes of NMDAR agents have now been
      identified that are positive or negative allosteric modulators (PAMs and NAMs,
      respectively) with various patterns of NMDAR subtype selectivity. These new
      agents act at several newly recognized binding sites on the NMDAR complex and
      offer significantly greater pharmacological control over NMDAR activity than
      previously available agents. The purpose of this review is to summarize the
      structure-activity relationships for these new NMDAR modulator drug classes and
      to describe the current understanding of their mechanisms of action.

PMID- 29446950
TI  - Isosteric Substitution of 4 H-1,2,4-Triazole by 1 H-1,2,3-Triazole in Isophthalic
      Derivative Enabled Hydrogel Formation for Controlled Drug Delivery.
AB  - In this work, we demonstrated that the simple substitution of the 1,2,4-triazole
      moiety in 5-( 4H-1,2,4-triazol-4-yl)isophthalic acid (5-TIA) by the 1 H-1,2,3
      triazol-5-yl unit enables the preparation of a hydrogelator (click-TIA). In sharp
      contrast to 5-TIA, its isostere click-TIA undergoes self-assembly in water upon
      sonication, leading to the formation of stable supramolecular viscoelastic
      hydrogels with a critical gelation concentration of 6 g/L. Hydrogels made of
      click-TIA as well as hybrid hydrogels made of the mixture click-TIA + 5-TIA
      (molar ratio 1:0.2) were used to compare different properties of the materials
      (i.e., rheological properties, thermal properties, mechanical stability,
      morphology). In terms of toxicity, neither click-TIA nor 5-TIA showed cytotoxic
      effects on cellular viability of HeLa cells up to 2.3 * 10-3 g/L when compared to
      untreated cells incubated with DMSO. Furthermore, the hydrogels were used for the
      encapsulation and in vitro controlled release of oxytetracycline that followed
      first-order kinetics. For the hydrogel made of click-TIA, a maximum drug release
      of ~60% was reached after ~8 h within a pH range between 6.5 and 10. However, the
      release rate was reduced to approximately half of its value at pH values between
      1.2 and 5.0, whereas the use of hybrid hydrogels made of click-TIA + 5-TIA
      allowed to reduce the original rate at pH <= 6.5.

PMID- 29446951
TI  - Palladium Nanoparticle-Catalyzed Stereoretentive Cross-Coupling of Alkenyl
      Sulfides with Grignard Reagents.
AB  - Reaction conditions allowing a stereoretentive cross-coupling of alkenyl sulfides
      with Grignard reagents using ligand-free Pd catalysis are discussed here. The
      presence of an adequately positioned OH function is a key feature that allows a
      Mg-promoted Lewis acid activation of the mercaptide leaving group. This easy to
      implement procedure actually relies on an in situ generation of stable Pd
      nanoparticles by simply mixing Pd2(dba)3, the Grignard reagent, and the vinyl
      sulfide cross-coupling partner in THF. The efficiency of this procedure has been
      demonstrated in a natural product total synthesis context.

PMID- 29446952
TI  - Short, Gram-Scale Syntheses of beta- and gamma-Lycorane Using Two Distinct
      Photochemical Approaches.
AB  - The synthesis of two diastereomeric members of the lycorane alkaloid family is
      reported. Although the routes are quite different in their approach, both involve
      the use of photochemistry as a key step, enabling the synthesis of gram
      quantities in the case of beta-lycorane.

PMID- 29446953
TI  - Visible-Light-Induced External Radical-Triggered Annulation To Access CF2
      Containing Benzoxepine Derivatives.
AB  - A facile and diversified synthesis of functionalized CF2-containing benzoxepine
      derivatives via photoredox catalysis was achieved in this work. This novel
      protocol features broad substrate scope, mild reaction conditions, operational
      simplicity, easy scale-up, and versatile derivatization, which would facilitate
      its practical and broad applications in the construction of valuable and
      synthetically challenging heterocycles.

PMID- 29446954
TI  - Mechanism of Initial Stage of Pore Formation Induced by Antimicrobial Peptide
      Magainin 2.
AB  - Antimicrobial peptide magainin 2 forms pores in lipid bilayers, a property that
      is considered the main cause of its bactericidal activity. Recent data suggest
      that tension or stretching of the inner monolayer plays an important role in
      magainin 2-induced pore formation in lipid bilayers. Here, to elucidate the
      mechanism of magainin 2-induced pore formation, we investigated the effect on
      pore formation of asymmetric lipid distribution in two monolayers. First, we
      developed a method to prepare giant unilamellar vesicles (GUVs) composed of
      dioleoylphosphatidylglycerol (DOPG), dioleoylphosphatidylcholine (DOPC), and lyso
      PC (LPC) in the inner monolayer and of DOPG/DOPC in the outer monolayer. We
      consider that in these GUVs, the lipid packing in the inner monolayer was larger
      than that in the outer monolayer. Next, we investigated the interaction of
      magainin 2 with these GUVs with an asymmetric distribution of LPC using the
      single GUV method, and found that the rate constant of magainin 2-induced pore
      formation, kp, decreased with increasing LPC concentration in the inner
      monolayer. We constructed a quantitative model of magainin 2-induced pore
      formation, whereby the binding of magainin 2 to the outer monolayer of a GUV
      induces stretching of the inner monolayer, causing pore formation. A theoretical
      equation defining kp as a function of magainin 2 surface concentration, X,
      reasonably explains the experimental relationship between kp and X. This model
      quantitatively explains the effect on kp of the LPC concentration in the inner
      monolayer. On the basis of these results, we discuss the mechanism of the initial
      stage of magainin 2-induced pore formation.

PMID- 29446955
TI  - Modeling Gas Flow Dynamics in Metal-Organic Frameworks.
AB  - Modeling fluid flow dynamics in metal organic frameworks (MOFs) is a required
      step toward understanding mechanisms of their activity as novel catalysts,
      sensors, and filtration materials. We adapted a lattice Boltzmann model,
      previously used for studying flow dynamics in meso- and microporous media, to the
      nanoscale dimensions of the MOF pores. Using this model, rapid screening of
      permeability of a large number of MOF structures, in different crystallographic
      directions, is possible. The method was illustrated here on the example of an
      anisotropic MOF, for which we calculated permeability values in different flow
      directions. This method can be generalized to a large class of MOFs and used to
      design MOFs with the desired gas flow permeabilities.

PMID- 29446956
TI  - Carbonyl-Functionalized Cyclazines as Colorants and Air-Stable n-Type
      Semiconductors.
AB  - A series of pi-extended cycl[3,3,2]azines (3) bearing additional carbonyl groups
      were synthesized via aldol condensations. Two strong electron acceptor molecules
      (4 and 5), with low-lying LUMO energy levels of -3.99 and -3.95 eV, respectively,
      were obtained. Organic thin-film transistors (TFTs) based on the cyanated
      cyclazine derivatives 5 were fabricated by vapor deposition, exhibiting
      extraordinarily stable n-type semiconductor character under ambient condition
      with the highest electron mobility of 0.06 cm2 V-1 s-1 consistently for more than
      30 months.

PMID- 29446957
TI  - Vitamin Catalysis: Direct, Photocatalytic Synthesis of Benzocoumarins via (-)
      Riboflavin-Mediated Electron Transfer.
AB  - An operationally simple protocol is disclosed to facilitate entry to benzo-3,4
      coumarins directly from biaryl carboxylic acids without the need for substrate
      prefunctionalization. Complementary to classic lactonization strategies, this
      disconnection relies on the oxidation competence of photoactivated (-)-riboflavin
      (vitamin B2) to generate the heterocyclic core via photoinduced single electron
      transfer. Collectively, the inexpensive nature of the catalyst, ease of
      execution, and absence of external metal additives are a convincing endorsement
      for the incorporation of simple vitamins in contemporary catalysis.

PMID- 29446958
TI  - Density Functional Theory plus Hubbard U Study of the Segregation of Pt to the
      CeO2- x Grain Boundary.
AB  - Grain boundaries (GBs) can be used as traps for solute atoms and defects, and the
      interaction between segregants and GBs is crucial for understanding the
      properties of nanocrystalline materials. In this study, we have systematically
      investigated the Pt segregation and Pt-oxygen vacancies interaction at the ?3
      (111) GB in ceria (CeO2). The Pt atom has a stronger tendency to segregate to the
      ?3 (111) GB than to the (111) and (110) free surfaces, but the tendency is weaker
      than to (112) and (100). Lattice distortion plays a dominant role in Pt
      segregation. At the Pt-segregated-GB (Pt@GB), oxygen vacancies prefer to form
      spontaneously near Pt in the GB region. However, at the pristine GB, oxygen
      vacancies can only form under O-poor conditions. Thus, Pt segregation to the GB
      promotes the formation of oxygen vacancies, and their strong interactions enhance
      the interfacial cohesion. We propose that GBs fabricated close to the surfaces of
      nanocrystalline ceria can trap Pt from inside the grains or other types of
      surface, resulting in the suppression of the accumulation of Pt on the surface
      under redox reactions, especially under O-poor conditions.

PMID- 29446959
TI  - Dissected Nucleus-Independent Chemical Shift Analysis of pi-Aromaticity and
      Antiaromaticity.
AB  - Analysis of the basic pi-aromatic (benzene) and antiaromatic (cyclobutadiene)
      systems by dissected nucleus-independent chemical shifts (NICS) shows the
      contrasting diatropic and paratropic effects, but also reveals subtleties and
      unexpected details.

PMID- 29446960
TI  - Improving adjustment and resilience in children following a disaster: Addressing
      research challenges.
AB  - There is compelling evidence of the potential negative effects of disasters on
      children's adjustment and functioning. Although there is an increasing base of
      evidence supporting the effectiveness of some interventions for trauma following
      disaster, more research is needed, particularly on interventions that can be
      delivered in the early aftermath of disaster as well as those that can address a
      broader range of adjustment difficulties such as bereavement that may be
      experienced by children after a disaster. This article identifies gaps in the
      knowledge of how best to intervene with children following disasters. Key
      challenges in conducting research in disaster contexts, including obtaining
      consent, designing rigorous studies, and obtaining funding quickly enough to
      conduct the study, are discussed. Several strategies hold promise to address
      research challenges in disasters, including using alternative designs (e.g.,
      propensity scores, matched control groups, group-level assignment), working with
      schools and communities, and studying implementation of nontraditional modes of
      intervention delivery. (PsycINFO Database Record

PMID- 29446961
TI  - Psychopathic men: Deficits in general mental ability, not emotion perception.
AB  - Psychopathy is characteristically associated with deficits in emotion perception;
      however, findings surrounding this deficit are actually quite mixed. This is most
      likely due to limitations of study methodology, including the use of tasks with
      unknown or poor psychometric properties, underpowered samples, and a lack of
      control for third variables. We present a study that addressed these limitations.
      A sample of men (n = 339) ranging across the psychopathy continuum, recruited in
      and out of the German prison system, completed three psychometrically validated
      tasks that assessed the ability to perceive facially expressed emotions. Using
      latent variable modeling, we show that deficits in emotion perception ability
      associated with psychopathy are fully attributable to deficits in general mental
      ability. Modeling relations at the manifest level, separately for inmates and
      noninmates, support these conclusions. We conclude that emotion general and
      emotion-specific deficits associated with psychopathy have been exaggerated and
      instead indicate deficits in general mental ability. (PsycINFO Database Record

PMID- 29446962
TI  - Borderline personality features and integration of positive and negative thoughts
      about significant others.
AB  - Taking the bad with the good is a necessity of life, and people who readily
      integrate thoughts of their loved one's flaws with thoughts of their more
      positive attributes maintain more stable, satisfying relationships. Borderline
      personality disorder, however, is often characterized by interpersonal
      perceptions that fluctuate between extremes of good and bad. We used a timed
      judgment task to examine information processing about significant others in
      individuals high in borderline personality features relative to healthy
      individuals and those high in avoidant personality features. In Study 1, when
      judging traits of a liked significant other, same-valence facilitation by
      negative primes (judging negative traits faster than positive traits after a
      negative prime) was significantly stronger in the borderline features group than
      the other two groups, and was inversely associated with self-reports of
      integrated thoughts about significant others. In contrast, same-valence
      facilitation by positive primes (judging positive traits faster than negative
      traits after a positive prime) was significantly stronger in the avoidant
      features group than the other two groups, and inversely associated with self
      esteem. No between-group differences in same-valence facilitation were
      statistically significant when participants judged traits of disliked significant
      others, liked foods, and disliked foods. In Study 2, same-valence facilitation by
      negative primes when judging traits of a liked significant other was
      significantly associated with less integrated positive/negative thoughts about
      that person in a 12-day diary. These results identify an implicit information
      processing pattern relevant to interpersonal difficulties in borderline
      personality disorder. (PsycINFO Database Record

PMID- 29446963
TI  - The effect of data points per x- to y-axis ratio on visual analysts evaluation of
      single-case graphs.
AB  - Research based on single-case designs (SCD) are frequently utilized in
      educational settings to evaluate the effect of an intervention on student
      behavior. Visual analysis is the primary method of evaluation of SCD, despite
      research noting concerns regarding reliability of the procedure. Recent research
      suggests that characteristics of the graphic display may contribute to poor
      reliability and overestimation of intervention effects. This study investigated
      the effect of increasing or decreasing the data points per x- to y-axis ratio
      (DPPXYR) on rater evaluations of functional relation and effect size in SCD data
      sets. Twenty-nine individuals (58.6% male) with experience in SCD were asked to
      evaluate 40 multiple baseline data sets. Two data sets reporting null, small,
      moderate, and large intervention effects (8 total) were modified by manipulating
      the ratio of the x- to y-axis (5 variations), resulting in 40 total graphs.
      Results indicate that raters scored effects as larger as the DPPXYR decreased.
      Additionally, a 2-way within-subjects analysis of variance (ANOVA) revealed a
      significant main effect of DPPXYR manipulation on effect size rating, F(2.11,
      58.98) = 58.05, p < .001, eta2 = .675, and an interaction between DPPXYR
      manipulation and magnitude of effect, F(6.71, 187.78) = 11.45, p < .001, eta2 =
      .29. Overall, results of the study indicate researchers and practitioners should
      maintain a DPPXYR of .14 or larger in the interest of more conservative effect
      size judgments. (PsycINFO Database Record

PMID- 29446964
TI  - Gender and age interact to predict the development of posttraumatic stress
      disorder symptoms following a motor vehicle accident.
AB  - OBJECTIVE: Women have a greater overall risk of developing posttraumatic stress
      disorder (PTSD) than men after exposure to trauma. In addition to gender, other
      sociodemographic factors have been identified as risk factors for PTSD; however,
      research has typically examined these factors separately. Age has been found to
      contribute to the development of psychiatric disorders, and both linear and
      curvilinear relationships have been reported between age and risk of developing
      PTSD. Recent research has suggested that this relationship may vary depending on
      gender. METHOD: We performed a secondary analysis of data from a prospective
      study of 287 (164 men, 123 women) motor vehicle accident (MVA) patients (aged 18
      81) who completed clinical interviews 6 weeks, 6 months, and/or 1 year after an
      MVA. RESULTS: Overall, women developed more severe PTSD symptoms than men;
      however, gender differences were small in the young (18-24 years) and the old (55
      and older) groups. In women, age was not associated with PTSD symptoms at 6 weeks
      and 6 months; however, age was curvilinearly associated with PTSD severity at 1
      year post-MVA such that middle-aged women reported greater symptom severity than
      younger and older women. Prior trauma exposure and social support mediated this
      relationship. In men, PTSD severity was not associated with age, but was related
      to income and social support. CONCLUSIONS: These findings highlight age-based
      subgroups of women at elevated risk for PTSD following a traumatic injury and
      suggest that psychosocial intervention with middle-aged women following trauma
      exposure may help reduce the risk of persistent PTSD symptoms. (PsycINFO Database
      Record

PMID- 29446966
TI  - When divided attention fails to enhance memory encoding: The attentional boost
      effect is eliminated in young-old adults.
AB  - In the Attentional Boost Effect (ABE), images or words presented with to-be
      responded target squares are later recognized more accurately than images or
      words presented with to-be-ignored distractor squares. Surprisingly, previous
      studies investigating the ABE have always examined young participants: thus, the
      question of whether this memory facilitation can be also observed in older adults
      has never been tested. The present study sought to fill this gap by examining
      whether healthy aging modulated the size of the ABE in 4 experiments in which the
      nature of the background stimuli (images vs. words), the length of the encoding
      trials (500 vs. 1,000 ms), and the type of instructions given to participants
      (incidental vs. intentional) were varied. In all cases, the results showed that
      the ABE was robust and significant in younger adults, whereas it was completely
      abolished in older adults. It is suggested that the detection of target squares
      required more attention resources in older than in younger adults, and that these
      resources were subtracted from the encoding of target-associated stimuli; thus,
      reducing or eliminating the ABE in the older group. Alternative explanations are
      also discussed. (PsycINFO Database Record

PMID- 29446967
TI  - Perceived control and frailty: The role of affect and perceived health.
AB  - Mechanisms underlying prospective associations of perceived control with frailty
      and other health outcomes are not well understood. In the present study we used 3
      waves of data from the Health and Retirement Study (N = 2,127) to test potential
      psychological and biological pathways linking perceived control with frailty over
      an 8-year period, and whether 4-year change in control predicts frailty
      independent of initial control. Lower odds of increasing frailty were associated
      with higher initial levels of perceived control (odds ratio [OR] = .74, p < .001,
      95% confidence interval [CI] [.65, .83]) and a more positive change in perceived
      control (OR = .82, p = .006, 95% CI [.73, .92]), independent of the personality
      traits neuroticism and conscientiousness. In cross-lagged mediation models, the
      association of initial perceived control with frailty was partially mediated by
      positive affect, negative affect, and self-rated health, but not C-reactive
      protein or allostatic load. Associations of perceived control with positive and
      negative affect were bidirectional, with mediation in both directions. Initial
      frailty status was not related to 4-year change in perceived control. Perceived
      control may affect frailty risk through influences on affective states as well as
      perceived health. Findings also extend evidence that changes in perceived control
      may be prognostic of future health outcomes in older adults. (PsycINFO Database
      Record

PMID- 29446965
TI  - Associations between coherent neural activity in the brain's value system during
      antismoking messages and reductions in smoking.
AB  - OBJECTIVE: Worldwide, tobacco use is the leading cause of preventable death and
      illness. One common strategy for reducing the prevalence of cigarette smoking and
      other health risk behaviors is the use of graphic warning labels (GWLs). This has
      led to widespread interest from the perspective of health psychology in
      understanding the mechanisms of GWL effectiveness. Here we investigated
      differences in how the brain responds to negative, graphic warning label-inspired
      antismoking ads and neutral control ads, and we probed how this response related
      to future behavior. METHOD: A group of smokers (N = 45) viewed GWL-inspired and
      control antismoking ads while undergoing fMRI, and their smoking behavior was
      assessed before and one month after the scan. We examined neural coherence
      between two regions in the brain's valuation network, the medial prefrontal
      cortex (MPFC) and ventral striatum (VS). RESULTS: We found that greater neural
      coherence in the brain's valuation network during GWL ads (relative to control
      ads) preceded later smoking reduction. CONCLUSIONS: Our results suggest that the
      integration of information about message value may be key for message influence.
      Understanding how the brain responds to health messaging and relates to future
      behavior could ultimately contribute to the design of effective messaging
      campaigns, as well as more broadly to theories of message effects and persuasion
      across domains. (PsycINFO Database Record

PMID- 29446968
TI  - Aging and altruism in intertemporal choice.
AB  - In addition to making decisions about gains and losses that affect only
      ourselves, we often make decisions that affect others. Research on life span
      changes in motivation suggests that altruistic motives become stronger with age,
      but no prior research has examined how altruism affects tolerance for temporal
      delays. Experiment 1 used a realistic financial decision making task involving
      choices for gains, losses, and donations. Each decision required an intertemporal
      choice between a smaller-immediate and a larger-later option. Participants more
      often chose the larger-later option in the context of donations than in the
      context of losses; thus, parting with more of their overall capital when the act
      of doing so benefited a charity. As predicted, the magnitude of this "altruism
      effect" was amplified in older relative to younger adults. This pattern was
      replicated in a second experiment that was conducted online to minimize the
      influence of demand characteristics. Overall, these findings add to the
      literature on an age-related increase in altruism, and are the first to
      demonstrate its effects on intertemporal choice. (PsycINFO Database Record

PMID- 29446969
TI  - Age-related changes in emotional qualities of the social network from middle
      adulthood into old age: How do they relate to the experience of loneliness?
AB  - Research shows that people maintain fewer social ties and social activities when
      they grow older. There appears, however, to be little variation in the average
      loneliness level from middle adulthood into old age. In this study we investigate
      to what extent beneficial changes in emotional qualities of the social network
      (SNW; number of distressing relationships, number of pleasant relationships,
      relationship satisfaction) may help to prevent an age-related increase in
      loneliness. We concentrate in particular on the question as to whether these
      emotional qualities become more relevant for predicting loneliness when people
      grow older. Data for this study comes from 10,900 participants of the German
      Ageing Survey (DEAS) that have been observed over up to 9 years of study. The
      dynamics of emotional qualities of the SNW and loneliness are examined over a
      broad age range of 40 to 84 years by using an accelerated longitudinal data
      design. The results of our analyses suggest that age-related changes in emotional
      qualities of the SNW are marked by both gains and losses. On the one hand, people
      report fewer distressing ties and a higher satisfaction with family relations
      when they grow older. On the other hand, older adults are less satisfied with
      their friendships and acquaintances. The number of pleasant ties demonstrates
      little variation with age. All emotional qualities of the SNW considered in this
      study were found to be relevant for predicting a person's level of loneliness.
      Other than expected, however, predictive effects were similar over age groups.
      (PsycINFO Database Record

PMID- 29446970
TI  - Age differences in emotional responses to monetary losses and gains.
AB  - People of all ages face events that threaten their well-being, but theories of
      aging posit that older adults will cope better. In a gamble with randomly
      assigned losses (vs. gains), older adults reported relatively less negative and
      more positive emotions than younger adults, especially after losses (vs. gains).
      Avoiding preoccupation with negative thoughts was more likely among older (vs.
      younger) adults and was related to less negative emotions after losses (vs.
      gains). A focus on limited time was associated with more positive emotions across
      all participants. Our findings may inform interventions that aim to promote
      emotional well-being across all ages. (PsycINFO Database Record

PMID- 29446971
TI  - Preserved neural event segmentation in healthy older adults.
AB  - An important feature of action understanding is that comprehenders segment the
      perceptual stream into events. Event segmentation dynamically engages a network
      of brain regions that likely play a role in how events are encoded. Here, in a
      sample of older adults, we assessed the relationship between changes in brain
      dynamics during movie watching and event understanding performance. Forty healthy
      older adults and a comparison sample of 12 younger adults passively viewed short
      movies of everyday activities while their brain activity was measured with fMRI.
      Afterward, they segmented the movies into events and performed memory tasks for
      movie content. The older adults engaged a similar event segmentation network
      during movie watching as the younger adults. Individual differences analyses
      revealed that although behavioral measures of event segmentation predicted
      memory, activity in the segmentation network did not. Intersubject correlation
      analyses revealed that normative brain dynamics during viewing in the right
      posterior temporal sulcus and left dorsolateral prefrontal cortex predicted
      better segmentation performance. These data suggest that these regions play an
      important role in event understanding, and also that the event segmentation
      network is preserved in healthy aging. (PsycINFO Database Record

PMID- 29446972
TI  - Editorial.
AB  - This editorial serves as an introduction for the new editorial team of the
      Journal of Comparative Psychology which is shifting from Chief Editor Josep Call
      and Associate Editor Irene Pepperberg to Chief Editor Dorothy Munkenbeck Fragaszy
      and Associate Editor Todd Freeberg. (PsycINFO Database Record

PMID- 29446973
TI  - A new look at play fighting.
AB  - With this issue, the editors inaugurate the Featured Article Essay in the
      Journalof Comparative Psychology. This brief essay, written by one or both of the
      editors, highlights one of the articles in each issue that is found to be
      particularly important, interesting, or innovative. The editors' choice for this
      issue is the article by Pellis and Pellis (2018) about play fighting in gray
      mouse lemurs (Microcebus murinus). (PsycINFO Database Record

PMID- 29446974
TI  - Error reduction in the finite helical axis for knee kinematics.
AB  - Traditionally the FHA is calculated stepwise between data points (sFHA),
      requiring down sampling to achieve a sufficiently large step size to minimize
      error. This paper proposes an alternate FHA calculation approach (rFHA), using a
      unique reference position to reduce error associated with small rotation angles.
      This study demonstrated error reduction using the rFHA approach relative to the
      sFHA approach. Furthermore, the rFHA in the femur is defined at each time point
      providing a continuous representation of joint motion. These characteristics
      enable the rFHA to quantify small differences in knee joint motion, providing an
      excellent measure to quantify knee joint stability.

PMID- 29446975
TI  - Primary adrenal insufficiency due to hereditary apolipoprotein AI amyloidosis:
      endocrine involvement beyond hypogonadism.
AB  - Several mutations in the gene encoding apolipoprotein AI (apoAI) have been
      described as a cause of familial amyloidosis. Individuals with apoAI-derived
      (AApoAI) amyloidosis frequently manifest with liver, kidney, laryngeal, skin and
      myocardial involvement. Although primary hypogonadism (PH) is considered almost
      pathognomonic of this disease, until now, primary adrenal insufficiency (PAI) has
      not been described as a common clinical feature. Here, we report the first
      kindred with AApoAI amyloidosis in which PAI is well-documented. All family
      members with the Leu60_Phe71delins60Val_61Thr heterozygous mutation who were
      regularly followed-up at our centre were considered. Nineteen individuals had the
      confirmed APOA1 deletion/insertion mutation, with detailed medical records
      available in 11 cases. Of these, 6 had PAI and 3 (all males) had PH. Among them,
      one 47-year-old man, not previously diagnosed with PAI, developed adrenal crisis
      after liver transplantation, precipitated by an opportunistic infection.
      Transplantation due to organ failure, which necessitates use of immunosuppressive
      medication such as corticosteroids, is frequently required during the course of
      hereditary amyloidosis. Consequently, PAI can remain masked, being discovered
      only when an adrenal crisis develops. Therefore, according to the present
      evidence, patients with AApoAI amyloidosis should be submitted to regular testing
      of corticotrophin and cortisol levels in order to avoid delaying corticosteroid
      replacement.

PMID- 29446976
TI  - Efficient biosynthesis, analysis, solubility and anti-bacterial activities of
      succinylglycosylated naringenin.
AB  - A novel water-soluble flavonoid with good anti-bacterial activities, naringenin
      6"-succl-7-O-glucoside (7-SGN), was synthesised. It was biotransformed from
      naringenin by Bacillus amyloliquefaciens FJ18 in aqueous miscible organic media,
      and characterised by LC-MS and NMR analysis. The solubility of 7-SGN in water was
      approximately 102 times higher than that of naringenin. These results
      demonstrated that both the water solubility and the anti-bacterial activity of 7
      SGN were significantly improved.

PMID- 29446977
TI  - Establishment, Growth, Proliferation, and Gene Expression of Buffalo (Bubalus
      bubalis) Transgenic Fetal Fibroblasts Containing Human Insulin Gene, and
      Production of Embryos by Handmade Cloning Using These Cells.
AB  - The aim of the present study was to compare transgenic cells, containing human
      insulin gene kept under the control of mammary gland-specific buffalo beta
      lactoglobulin promoter, and their counterparts, that is, nontransgenic cells, for
      examining their potential for the production of embryos following somatic cell
      nuclear transfer (SCNT). The gene construct was delivered into buffalo fetal
      fibroblasts (BFF) by nucleofection following which, the transfected cells were
      selected by culture in the presence of G418 for 3 weeks. Transgene integration
      into BFF genome was confirmed by polymerase chain reaction (PCR) and reverse
      transcriptase PCR. At passage 8-10, the growth rate, cell proliferation rate, and
      quantitative expression of certain genes were compared between transgenic and
      nontransgenic cells. The growth rate and cell proliferation rate was
      significantly lower (p < 0.05) for transgenic than for nontransgenic cells. Using
      quantitative real-time PCR it was found that the expression level of CASPASE 3,
      CASPASE 9, BAX, and P53 was significantly higher (p < 0.05) and that of HDAC1 and
      IGF-1R was significantly lower (p < 0.05) in transgenic compared with
      nontransgenic cells. The differences in the relative expression level of BCL-XL,
      MCL-1, DNMT1, DNMT3a, GDF9, FGF2, and G6PD between the two groups were not
      significant. Furthermore, when the two cell types were used as donor cells for
      production of embryos by handmade cloning, the blastocyst rate was significantly
      lower (p < 0.05) with transgenic (35.69% +/- 1.78%) than with nontransgenic cells
      (48.75% +/- 2.38%). In conclusion, these results indicate that differences were
      present between transgenic and nontransgenic cells, which may affect the
      efficiency of SCNT when used as donor cells.

PMID- 29446978
TI  - Supratentorial extension of large cerebellar pilocytic astrocytoma in adult.
AB  - A Neuroimage of a cerebellar pilocytic astrocytoma with supratentorial extension
      in a 26 year old male illustraiting how slow growing brain tumours expand
      respecting dural but not neural barriers.

PMID- 29446979
TI  - Synovial sarcoma mimicking a thoracic dumbell schwannoma- a case report.
AB  - INTRODUCTION: Synovial sarcoma is a rare mesenchymal malignant neoplasm that
      accounts for less than 10% of soft tissue sarcomas. About 95% of the sarcomas
      occur in the extremities. Primary synovial sarcomas of the spine are a rare tumor
      arising from the paravertebral regions, paraspinal muscles or epidural spaces.
      PURPOSE: To report an atypical radiological presentation of synovial sarcoma of
      the thoracic spine mimicking a nerve sheath tumor in an elderly adult and
      describe the management with review of the literature. CLINICAL PRESENTATION: A
      forty-six-year-old lady presented with clinical features of a thoracic intradural
      extramedullary cord compression at T7 level. She was Nurick grade 4 at
      presentation. MRI of the Thoracic spine with whole spine screening showed a
      contrast enhancing intradural extramedullary tumor at the T7-8 level; the tumor
      was exiting out through the left T7-8 neural foramina with foraminal widening.
      The possibility of a schwannoma was considered. INTERVENTION: She underwent a T7
      8 laminectomy and total excision of the tumor followed by posterior fusion. The
      biopsy was reported as synovial sarcoma. She subsequently underwent radiation and
      chemotherapy. She had marked improvement in her Neurological status and remained
      disease free at six months follow-up. CONCLUSION: Synovial sarcoma of the spine
      is a rare mesenchymal malignant neoplasm. One needs to consider Synovial sarcoma
      as one of the differential diagnosis of intradural tumors of the spine.

PMID- 29446980
TI  - Best Use of Models to Advance the Artificial Pancreas.

PMID- 29446982
TI  - Development of an omentum-cultured oesophageal scaffold reinforced by a 3D
      printed ring: feasibility of an in vivo bioreactor.
AB  - Current treatments of oesophageal diseases, such as carcinoma, congenital
      abnormality or trauma, require surgical intervention and oesophageal
      reconstruction with the stomach, jejunum or colon. However, serious side effects
      are possible with each treatment option. Despite tissue engineering promising to
      be an effective regenerative strategy, no functional solution currently exists
      for oesophageal reconstruction. Here, we developed an omentum-cultured
      oesophageal scaffold reinforced by a 3D-printed ring. The nano-structured
      scaffolds were wrapped into the omentum of rats and orthotopically transplanted
      for the repair of circumferential oesophageal defects two weeks later. The
      artificial oesophagus exhibited complete healing of the surgically created
      circumferential defects by the second week. The integration of the omentum
      cultured oesophageal scaffold and the regenerative tissue remained intact.
      Macroscopically, there was no evidence of a fistula, perforation, abscess
      formation or surrounding soft-tissue necrosis. The omentum-cultured nano
      structure scaffold reinforced by a 3D-printed ring is a more practical model with
      better vascularization for artificial neo-oesophagus reconstruction in a rat
      model.

PMID- 29446981
TI  - Diet Pattern and Respiratory Morbidity in the Atherosclerosis Risk in Communities
      Study.
AB  - RATIONALE: Dietary intake is a potential risk factor for respiratory morbidity in
      adult populations. Few studies capture the effect of dietary patterns,
      representative of the combination of nutrients consumed, on self-reported
      respiratory morbidity in combination with objective measures of lung function.
      OBJECTIVES: To evaluate patterns of dietary intake in relation to respiratory
      morbidity and objective measures of lung function in a U.S. POPULATION:  METHODS:
      The ARIC (Atherosclerosis Risk in Communities) study investigators enrolled
      15,792 participants from four U.S. communities between 1987 and 1989 and
      collected data using a validated food frequency questionnaire to assess diet.
      Principal component analysis was applied, and patterns representative of
      "Western" and "Prudent" diets emerged. We investigated cross-sectional
      associations between dietary patterns and pulmonary assessments that included
      asthma and chronic obstructive pulmonary disease (COPD) diagnosis, respiratory
      symptoms, and lung function. Multivariable Poisson regression models included
      quintiles of dietary patterns and potential confounders. Interaction of dietary
      patterns with obesity, sex, and smoking status was assessed in relation to all
      outcomes. RESULTS: Higher scores in the "Western" dietary pattern (quintile 5 vs.
      quintile 1) were associated with higher prevalence of COPD (prevalence ratio
      [PR], 1.62; 95% confidence ratio [CI], 1.33-1.97), wheeze (PR, 1.37; 95% CI, 1.11
      1.69), cough (PR, 1.32; 95% CI, 1.32-1.59), and phlegm (PR, 1.27; 95% CI, 1.05
      1.54) and lower percent predicted forced expiratory volume in 1 second (FEV1),
      percent predicted forced vital capacity (FVC), and FEV1/FVC ratio. Higher scores
      in the "Prudent" dietary pattern (quintile 5 vs. quintile 1) were associated with
      lower prevalence of COPD (PR, 0.82; 95% CI, 0.70-0.95) and cough (PR, 0.77; 95%
      CI, 0.67-0.89) and higher percent predicted FEV1 and FEV1/FVC ratio. The
      prevalence of asthma was not related to dietary intake. CONCLUSIONS: A "Western"
      dietary pattern was associated with respiratory symptoms, lower lung function,
      and COPD in ARIC participants.

PMID- 29446983
TI  - Multi-Objectivising Combinatorial Optimisation Problems by Means of Elementary
      Landscape Decompositions.
AB  - In the last decade, many works in combinatorial optimisation have shown that, due
      to the advances in multi-objective optimisation, the algorithms from this field
      could be used for solving single-objective problems as well. In this sense, a
      number of papers have proposed multi-objectivising single-objective problems in
      order to use multi-objective algorithms in their optimisation. In this article,
      we follow up this idea by presenting a methodology for multi-objectivising
      combinatorial optimisation problems based on elementary landscape decompositions
      of their objective function. Under this framework, each of the elementary
      landscapes obtained from the decomposition is considered as an independent
      objective function to optimise. In order to illustrate this general methodology,
      we consider four problems from different domains: the quadratic assignment
      problem and the linear ordering problem (permutation domain), the 0-1
      unconstrained quadratic optimisation problem (binary domain), and the frequency
      assignment problem (integer domain). We implemented two widely known multi
      objective algorithms, NSGA-II and SPEA2, and compared their performance with that
      of a single-objective GA. The experiments conducted on a large benchmark of
      instances of the four problems show that the multi-objective algorithms clearly
      outperform the single-objective approaches. Furthermore, a discussion on the
      results suggests that the multi-objective space generated by this decomposition
      enhances the exploration ability, thus permitting NSGA-II and SPEA2 to obtain
      better results in the majority of the tested instances.

PMID- 29446984
TI  - Anticancer Drugs as Antibiofilm Agents in Candida albicans: Potential Targets.
AB  - The human pathogen Candida albicans can grow as a biofilm on host tissues and on
      the surfaces of different prosthetic devices in a patient's body. Various studies
      have reported that biofilms formed by C. albicans are resistant to most of the
      currently used antibiotics including the widely prescribed drug, fluconazole. As
      such, novel strategies for the treatment of drug-resistant biofilms are required.
      Drug repositioning or the use of drugs outside their unique indication has the
      potential to radically change drug development. We have tested 16 anticancer
      drugs for their activities against C. albicans. For the first time, we are
      reporting repositioning of anticancer drugs as potential antibiofilm agents in C.
      albicans. Nine categories of drugs with different chemical modes of action
      effectively inhibited biofilms at a concentration range of 0.25-4 mg/mL,
      establishing their potential for the inhibition of biofilms. Human genes targeted
      by these drugs show significant identity with their homologous genes in C.
      albicans at the amino acid as well as nucleotide levels. This study indicates
      that anticancer drugs could be potential candidates for repositioning as anti
      Candida biofilm agents.

PMID- 29446985
TI  - Comparison of pore water samplers and cryogenic distillation under laboratory and
      field conditions for soil water stable isotope analysis.
AB  - We used pore water samplers (PWS) to sample for isotope analysis (1) only water,
      (2) soil under laboratory conditions, and (3) soil in the field comparing the
      results with cryogenic extraction (CE). In (1) and (2), no significant
      differences between source and water extracted with PWS were detected with a mean
      absolute difference (MAD) always lower than 2 0/00 for delta2H and 1 0/00 for
      delta18O. In (2), CE water was more enriched than PWS-extracted water, with a MAD
      respect to source water of roughly 8 0/00 for delta2H and 4 0/00 for delta18O. In
      (3), PWS water was enriched relative to CE water by 3 0/00 for delta2H and 0.9
      0/00 for delta18O. The latter result may be due to the distinct water portions
      sampled by the two methods. Large pores, easily sampled by PWS, likely retain
      recent, and enriched, summer precipitation while small pores, only sampled by CE,
      possibly retain isotopically depleted water from previous winter precipitation or
      irrigation inputs. Accuracy and precision were greater for PWS relative to CE.
      PWS is therefore suggested as viable tool to extract soil water for stable
      isotope analysis, particularly for soils used in this study (sandy and silty
      loams).

PMID- 29446986
TI  - An Intercenter Comparison of Nasolabial Appearance Including a Center Using
      Nasoalveolar Molding.
AB  - OBJECTIVE: To compare nasolabial appearance outcomes of patients with complete
      unilateral cleft lip and palate (CUCLP) in preadolescence from 4 cleft centers
      including a center using nasoalveolar molding (NAM) and primary nasal
      reconstruction. DESIGN: Retrospective cohort study. SETTING: Four cleft centers
      in North America. PATIENTS: 135 subjects with repaired CUCLP. METHODS: Frontal
      and profile facial pictures were assessed using the Asher-McDade rating scale.
      Intra- and interrater reliability were tested using weighted Kappa statistics.
      Median scores by center were compared with Kruskal-Wallis statistics. RESULTS:
      Intrarater reliability scores were moderate to good. Interrater reliability
      scores were moderate. Significant differences ( P < .05) among centers were
      found. For nasal form, center G (median = 2.83) had better scores than centers C
      and D (C median = 3.33, D median = 3.17). For nose symmetry, center G had better
      scores (median = 2.33) than all other centers (B median = 2.67, C median = 2.83,
      D median = 2.83). For vermillion border, center G had better scores (median =
      2.58) than centers B and C (B median = 3.17, C median = 3.17). For nasolabial
      profile, center G (median score = 2.67) had better scores than center C (median =
      3.00). For total nasolabial score, center G (median = 2.67) had better scores
      than all other centers (B median = 2.83, C median = 3, D median = 2.83).
      CONCLUSION: The protocol followed by center G, the only center that performed NAM
      and primary nasal reconstruction, produced better results in all categories when
      compared to center C, the only center that did not perform presurgical
      orthopedics or lip/nose revisions. When compared to centers that performed
      traditional presurgical orthopedics and surgical revisions (B and D), center G
      was not consistently better in all categories. As with other uncontrolled,
      retrospective intercenter studies, it is not possible to attribute the outcomes
      to a specific protocol component.

PMID- 29446987
TI  - Dexmedetomidine Decreases Postoperative Pain and Narcotic Use in Children
      Undergoing Alveolar Bone Graft Surgery.
AB  - OBJECTIVE: Dexmedetomidine is a parenteral agent that combines the benefits of
      cooperative sedation, anxiolysis, and analgesia without the risks of respiratory
      depression. Off-label use has been reported in children. We have introduced
      dexmedetomidine for use in patients having undergone alveolar bone graft (ABG).
      The objective is to demonstrate the value and safety of postoperative
      dexmedetomidine infusion in a non-ICU setting following ABG. DESIGN: A
      retrospective review was performed on patients who underwent ABG by the senior
      author. Patients were divided into 2 groups: those who received postoperative
      dexmedetomidine and those who received patient-controlled anesthesia. MAIN
      OUTCOME MEASURE(S): The primary study outcome measures included patient
      demographics, adverse events, length of stay, pain scores, and doses of narcotics
      during admission were collected. RESULTS: Inclusion criteria were met by 54
      patients; 39 received dexmedetomidine whereas 15 did not. There were no
      significant differences between groups in age, gender, and length of stay. The
      patients who received dexmedetomidine used oral narcotics less often ( P = .01).
      In addition, more patients reported no pain after surgery ( P = .05) and at the
      time of discharge if they received dexmedetomidine ( P < .01). There were no
      reported adverse effects. CONCLUSIONS: Dexmedetomidine provided superior pain
      control after surgery and at the time of discharge, as well as a significant
      decrease in the use of oral narcotics. In our institution, it has since replaced
      the PCA as a postoperative pain control modality. Absent the risk for respiratory
      depression, dexmedetomidine has demonstrated a safe option for postoperative pain
      control in our focused group of pediatric patients.

PMID- 29446988
TI  - Diagnosing Tongue Base Obstruction in Pierre Robin Sequence Infants: Sleep vs
      Awake Endoscopy.
AB  - OBJECTIVE: To investigate whether awake endoscopy can diagnose base-of-tongue
      obstruction as reliably as sleep endoscopy in infants with Pierre Robin sequence
      (PRS). DESIGN: The study was retrospective with the clinicians blinded to patient
      identity. Endoscopy findings were assessed and measured by the performing
      pediatric otolaryngologist. SETTING: Tertiary care children's hospital. PATIENTS:
      All infants with PRS managed between January 2005 and July 2015 were included.
      There were 141 patients, of which 35 underwent both awake endoscopy (AE) and drug
      induced sleep endoscopy (DISE). INTERVENTIONS: Bedside AE and DISE in the
      operating room. MAIN OUTCOME MEASURES: Presence of moderate or severe base-of
      tongue collapse was assessed. Sensitivity, specificity, and positive likelihood
      ratio of AE findings as well as intertest differences between AE and DISE were
      calculated. RESULTS: AE had 50.0% sensitivity (95% confidence interval [CI] 27.2%
      72.8%) and 86.7% specificity (95% CI 59.5%-98.3%) for detecting base-of-tongue
      obstruction compared to DISE; false negative rate was 50.0% (n = 10). Positive
      likelihood ratio was 3.75 (CI 0.96-14.65). Compared to AE, DISE demonstrated
      significantly more cases of base-of-tongue obstruction ( P = .039). CONCLUSIONS:
      Bedside AE has low sensitivity for detecting base-of-tongue collapse in infants
      with PRS. Because of the substantial false negative rate, AE may not be a
      reliable diagnostic modality for ruling out base-of-tongue obstruction in this
      susceptible population. DISE may be indicated in high-risk patients to avoid
      underdiagnosing upper airway obstruction.

PMID- 29446989
TI  - Comparison of the efficacy of two human fibrinogen concentrates to treat
      dilutional coagulopathy in vitro.
AB  - Both congenital and acquired fibrinogen deficiency can be safely treated with
      administration of fibrinogen concentrate. The aim of this study was to test the
      efficacy of a new fibrinogen product (Fibryga) compared to a licensed product
      (Haemocomplettan) in an in vitro model of dilutional coagulopathy. Ten blood
      specimens from healthy volunteers were diluted 1:1 with balanced crystalloid
      solution and subsequently supplemented with each fibrinogen concentrate at a dose
      replicating in vivo supplementation (50 mg kg-1). Changes in clot firmness
      (FIBTEM and EXTEM assay), as well as changes in the fibrinogen antigen level,
      fibrinogen activity, factor XIII level and fibronectin levels were assessed at
      baseline, after dilution and after adding fibrinogen concentrate. There was no
      significant difference between the drugs in their in vitro ability to improve
      clot firmness in the FIBTEM assay (Fibryga: mean MCF 14.4 mm (SD 3.4 mm) vs.
      Haemocomplettan: MCF 14.1 mm (2.4); p = .584). Fibryga led to significantly
      higher clot firmness in EXTEM MCF: 56.7 mm (3.8) vs. 53.7 mm (3.7); p < .001).
      Distinct differences between FXIII levels (significantly higher in Fibryga; mean
      40.9% (6.2%) vs. 31.0% (6.2%); p < .001) and fibronectin levels (significantly
      higher in Haemocomplettan; mean 0.008 g L-1 (SD 0.002 g L-1) vs. 0.002 g L-1 (SD
      0.002 g L-1; p < .001) were observed between products. This is the first study to
      demonstrate that Fibryga and Haemocomplettan have similar efficacy in improving
      clot firmness in a dilutional hypofibrinogenemia model in vitro.

PMID- 29446990
TI  - Rapid increases in nitrogen oxides are associated with acute myocardial
      infarction: A case-crossover study.
AB  - Aims High concentrations of air pollutants are associated with increased risk for
      myocardial infarction. The European Union has defined statutory limits for air
      pollutants based on upper absolute concentrations. We evaluated the association
      between rapid changes in air pollutants and the risk of myocardial infarction
      independently of absolute concentrations. Methods and results Using a hospital
      based case-crossover study, effects of 24h changes of nitrogen oxides (NOX/2),
      particulate matter (PM10), and ozone on the risk of myocardial infarction was
      assessed in 693 patients. In the overall population, increases of NOX of more
      than 20 ug/m3 within 24 h were associated with an increase in the risk of
      myocardial infarction by up to 121% (odds ratio (OR) 2.21, 95% confidence
      interval (CI) 1.19-4.08). Comparably, rapid increases of NO2 of more than 8 ug/m3
      tended to increase myocardial infarction risk by 73% (OR 1.73, 95% CI 0.91-3.28)
      while myocardial infarction risk decreased by 60% after a decrease of NO2
      concentration of more than 8 ug/m3 (OR 0.4, 95% CI 0.21-0.77), suggesting a close
      to-linear association. While results for ozone concentrations were ambiguous,
      rapid change in PM10 was not associated with myocardial infarction risk.
      Conclusion Dynamics and extent of increase in nitrogen oxide concentrations may
      be an independent risk factor for myocardial infarction. As there are currently
      no European Union statutory limits reflecting this dynamic variation of air
      pollutants on a daily basis, the results urgently call for confirming studies in
      different geographical regions to verify the observations.

PMID- 29446992
TI  - Anticandidal activity of bioinspired ZnO NPs: effect on growth, cell morphology
      and key virulence attributes of Candida species.
AB  - The pathogenicity of Candida species in human is dependent on a variety of
      virulence factor such as adhesion factors, germ tube and hyphal formation,
      secretion of hydrolytic phospholipases and proteinases and drug resistance
      biofilm. ZnO NPs have been synthesized by using leaf extract of Crinum latifolium
      and were characterized by UV-Vis spectrophotometer, FTIR, SEM, EDX and TEM. In
      this study for the first time, potent inhibitory effects of ZnO NPs on principal
      virulence factors of Candida albicans and non-albicans such as germ tube
      formation, secretion of hydrolytic phospholipases and proteinases and biofilm
      formation has been investigated. ZnO NPs remarkably reduced the germ tube
      formation of C. albicans at 1 (86.4%), 0.5 (75.0%), 0.25 (61.4%), 0.125 (34.1%)
      and 0.062 mg/ml (11.4%). ZnO NPs significantly lowered the phospholipase and
      proteinase secretion by 58.8 and 95.2% at 0.25 mg/ml, respectively. CSLM results
      showed that ZnO NPs suppressed biofilm formation up to 85% at 0.25 mg/ml. SEM and
      TEM micrograph showed that ZnO NPs penetrated inside the cell and causes
      extensive damaged in cell wall and cell membrane. Inhibition of Candida growth
      and various virulent factors by ZnO NPs provides an insight towards their
      therapeutic application for the treatment of Candida-associated infections.

PMID- 29446991
TI  - Fluid-structure interaction modeling of aneurysmal arteries under steady-state
      and pulsatile blood flow: a stability analysis.
AB  - Tortuous aneurysmal arteries are often associated with a higher risk of rupture
      but the mechanism remains unclear. The goal of this study was to analyze the
      buckling and post-buckling behaviors of aneurysmal arteries under pulsatile flow.
      To accomplish this goal, we analyzed the buckling behavior of model carotid and
      abdominal aorta with aneurysms by utilizing fluid-structure interaction (FSI)
      method with realistic waveforms boundary conditions. FSI simulations were done
      under steady-state and pulsatile flow for normal (1.5) and reduced (1.3) axial
      stretch ratios to investigate the influence of aneurysm, pulsatile lumen pressure
      and axial tension on stability. Our results indicated that aneurysmal artery
      buckled at the critical buckling pressure and its deflection nonlinearly
      increased with increasing lumen pressure. Buckling elevates the peak stress (up
      to 118%). The maximum aneurysm wall stress at pulsatile FSI flow was (29%) higher
      than under static pressure at the peak lumen pressure of 130 mmHg. Buckling
      results show an increase in lumen shear stress at the inner side of the maximum
      deflection. Vortex flow was dramatically enlarged with increasing lumen pressure
      and artery diameter. Aneurysmal arteries are more susceptible than normal
      arteries to mechanical instability which causes high stresses in the aneurysm
      wall that could lead to aneurysm rupture.

PMID- 29446993
TI  - Pre-Intensive Care Unit Cognitive Status, Subsequent Disability, and New Nursing
      Home Admission among Critically Ill Older Adults.
AB  - RATIONALE: Cognitive impairment is common among older adults, yet little is known
      about the association of pre-intensive care unit cognitive status with outcomes
      relevant to older adults maintaining independence after a critical illness.
      OBJECTIVES: To evaluate whether pre-intensive care unit cognitive status is
      associated with post-intensive care unit disability, new nursing home admission,
      and mortality after a critical illness among older adults. METHODS: In this
      prospective cohort study, 754 persons aged 70 years or more were monitored from
      March 1998 to December 2013 with monthly assessments of disability. Cognitive
      status was assessed every 18 months, using the Mini-Mental State Examination
      (range, 0-30), with scores classified as 28 or higher (cognitively intact), 24-27
      (minimal impairment), and less than 24 (moderate impairment). The primary outcome
      was disability count (range, 0-13), assessed monthly over 6 months after an
      intensive care unit stay. The secondary outcomes were incident nursing home
      admission and time to death after intensive care unit admission. The analytic
      sample included 391 intensive care unit admissions. RESULTS: The mean age was
      83.5 years. The prevalence of moderate impairment, minimal impairment, and intact
      cognition (the comparison group) was 17.3, 46.2, and 36.5%, respectively. In the
      multivariable analysis, moderate impairment was associated with nearly a 20%
      increase in disability over the 6-month follow-up period (adjusted relative risk,
      1.19; 95% confidence interval, 1.04-1.36), and minimal impairment was associated
      with a 16% increase in post-intensive care unit disability (adjusted relative
      risk, 1.16; 95% confidence interval, 1.02-1.32). Moderate impairment was
      associated with more than double the likelihood of a new nursing home admission
      (adjusted odds ratio, 2.37; 95% confidence interval, 1.01-5.55). Survival
      differed significantly across the three cognitive groups (log-rank P = 0.002),
      but neither moderate impairment (adjusted hazard ratio, 1.19; 95% confidence
      interval, 0.65-2.19) nor minimal impairment (adjusted hazard ratio, 1.00; 95%
      confidence interval, 0.61-1.62) was significantly associated with mortality in
      the multivariable analysis. CONCLUSIONS: Among older adults, any impairment (even
      minimal) in pre-intensive care unit cognitive status was associated with an
      increase in post-intensive care unit disability over the 6 months after a
      critical illness; moderate cognitive impairment doubled the likelihood of a new
      nursing home admission. Pre-intensive care unit cognitive impairment was not
      associated with mortality from intensive care unit admission through 6 months of
      follow-up. Pre-intensive care unit cognitive status may provide prognostic
      information about the likelihood of older adults maintaining independence after a
      critical illness.

PMID- 29446995
TI  - Secondary metabolites from the unique bamboo, Melocanna baccifera.
AB  - Phytochemistry of fruits and leaves of the unique bamboo Melocanna baccifera
      resulted in the isolation of 27 secondary metabolites, including 4
      Oxabicyclo[3.2.2]nona-1(7),5,8-triene and Verbacine. Biological activity studies
      of Verbacine revealed it as an inhibitor of acetylcholinesterase and as cytotoxic
      against C6 cancer cells.

PMID- 29446994
TI  - "It's Better in a Group Anyway": Patient Experiences of Group and Individual
      Acupuncture.
AB  - OBJECTIVES: Chronic pain is prevalent, burdensome, and costly, and there are
      ethnic and racial disparities in treatment. Acupuncture is effective and safe,
      but access is limited. Group acupuncture can decrease cost and increase capacity
      by decreasing clinic space needs and increasing patient volume per acupuncturist;
      however, the effectiveness and patient acceptability of group and individual
      session acupuncture have never been directly compared. DESIGN: The Acupuncture
      Approaches to Decrease Disparities in Pain Treatment (AADDOPT-2) study is a
      randomized comparative effectiveness trial of acupuncture for chronic pain.
      Semistructured in-depth interviews were conducted with a subset of patients
      enrolled in the trial. SETTINGS/LOCATION: Outpatient clinics in an urban, low
      income area serving a primarily black and Hispanic population. SUBJECTS:
      Qualitative interviews were conducted with 46 patients; 23 in each arm of the
      AADDOPT-2 study. INTERVENTIONS: Patients were randomized to receive either
      individual acupuncture or acupuncture delivered in a small group. OUTCOME
      MEASURES: Transcripts of the interviews were analyzed using an inductive thematic
      framework to explore and compare the patient experience in group and individual
      settings. RESULTS: Patients in both study arms valued the pain relief, improved
      quality of life, and relaxation experienced during acupuncture. Privacy and mixed
      sex groups were cited as a concern by a minority of patients; however, most of
      those randomized to the group setting noted that these concerns abated after
      initiating treatment. Differences between arms included the depth of the
      relationship with the acupuncturist and misgivings related to the treatment
      space. Group dynamics varied; some groups fostered a supportive, therapeutic
      interaction, while others were more reserved. CONCLUSIONS: Patients in both arms
      valued their acupuncture experience. Participants described both positive and
      negative aspects of the group setting.

PMID- 29446996
TI  - Recent Advances in Therapeutic Genome Editing in China.
AB  - Editing of the genome to correct disease-causing mutations is a promising
      approach for the treatment of human diseases. Recent advances in the development
      of programmable nuclease-based genome editing tools have substantially improved
      the ability to make precise changes in the human genome. Genome editing
      technologies are already being used to correct genetic mutations in affected
      tissues and cells to treat diseases that are refractory to traditional gene
      therapies. Chinese scientists have made remarkable breakthroughs in the field of
      therapeutic genome editing, particularly with the first clinical trial involving
      the clustered regularly interspaced short palindromic repeats-caspase 9 system
      that began in China. Herein, current progress toward developing programmable
      nuclease-based gene therapies is introduced, as well as future prospects and
      challenges in China.

PMID- 29446997
TI  - Double-Dose Adenovirus-Mediated Adjuvant Gene Therapy Improves Liver
      Transplantation Outcomes in Patients with Advanced Hepatocellular Carcinoma.
AB  - The present clinical trial assessed the effect of double-dose administration of
      replication-deficient adenovirus-thymidine kinase and ganciclovir (ADV-TK/GCV) in
      patients with advanced hepatocellular carcinoma (HCC) who underwent liver
      transplantation (LT). Eighty-six patients with single tumor diameters >5 cm or
      multiple tumors with diameters >3 cm each, regardless of vascular invasion, were
      examined over a follow-up period of 61 months. All patients underwent orthotopic
      LT; 43 received LT only, and 43 received LT plus double-dose ADV-TK/GCV gene
      therapy (LT + ADV-TK/GCV). Recurrence-free survival (RFS) and overall survival
      (OS) rates, as well as therapeutic safety, were assessed. The RFS and OS rates in
      LT + ADV-TK/GCV patients at 3 years (55.9% and 60.3%, respectively) were
      significantly higher than those in the LT-only group (13.5% and 19.3%,
      respectively; p < 0.001). LT + ADV-TK/GCV patients without vascular invasion
      showed significant improvement in RFS (73.7%) and OS (68.6%). LT + ADV-TK/GCV
      patients without extrahepatic vascular invasion experienced higher OS versus LT
      only patients. Double-dose ADV-TK/GCV gene therapy combined with LT was safe and
      improved RFS and OS in advanced HCC patients without vascular invasion over the 5
      year follow-up period. The potential to select patients with intrahepatic and
      extrahepatic vascular invasion for LT requires further confirmation.

PMID- 29446998
TI  - Considerations for Clinical Review of Cellular Therapy Products: Perspectives of
      the China Food and Drug Administration Center for Drug Evaluation.
AB  - With increasing numbers of technical developments and clinical studies,
      pioneering cellular/gene therapies are now available that could cure life
      threatening disease. Cellular/gene therapy products are broad-ranging and
      complicated, and thereby bring challenges for clinical review by regulatory
      agencies. This review discusses principles for the clinical review of cellular
      therapy products, including protection of clinical trial populations,
      pharmacodynamics, pharmacokinetics, dose evaluation, clinical efficacy, clinical
      safety, and risk-management plans. Based on these principles, key points in the
      clinical review of chimeric antigen receptor T-cell therapy are also discussed.

PMID- 29446999
TI  - Gene and Cell Therapy in China: Highlighting Excellence in the 21st Century : 21.

PMID- 29447000
TI  - Ghrelin prevents cardiac cell apoptosis during cardiac remodelling post
      experimentally induced myocardial infarction in rats via activation of Raf-MEK1/2
      ERK1/2 signalling.
AB  - CONTEXT: Mechanisms by which ghrelin affords its cardioprotection in mammals
      remained unclear. OBJECTIVE: To examine if ghrelin confers cardio-protection
      during cardiac remodelling post-MI by modulating the RAF-1-MEK1/2-ERK1/2
      signalling pathway. MATERIALS AND METHODS: Rats were divided into control, sham,
      sham + ghrelin, myocardial infarction (MI), and MI + ghrelin groups. Ghrelin (100
      ug/kg) was administered for 21 days, starting one-day post-MI. RESULTS: Ghrelin
      enhanced cardiac contractility and the activities of antioxidant enzymes, lowered
      serum levels of enzyme markers of cardiac dysfunction, and lowered inflammatory
      mediator levels. Ghrelin increased levels of phospho-Raf-1 (Ser338), phospho
      MEK1/2 (Ser217/221), phospho-ERK1/2 (Thr202/Tyr204), and of their downstream
      target p-BAD (Ser112) and inhibited the cleavage of caspase-3. Concomitantly,
      ghrelin prevented the increases in the levels of fibrotic markers, including
      alpha-smooth muscle actin (alpha-SMA), metalloproteinase-9 (MPP-9), and type III
      collagen. CONCLUSION: Post-MI in rats, ghrelin stimulated Raf-1-MEK1/2-ERK1/2-BAD
      signalling in the LV infarct areas, accounting for its anti-apoptotic effect,
      enhancing cardiac function, and inhibiting cardiac fibrosis during cardiac
      remodelling.

PMID- 29447001
TI  - New 2017 American Heart Association and American College of Cardiology guideline
      for hypertension in the adults: major paradigm shifts, but will they help to
      fight against the hypertension disease burden?

PMID- 29447002
TI  - Recent treatment modalities for cardiovascular diseases with a focus on stem
      cells, aptamers, exosomes and nanomedicine.
AB  - Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality
      worldwide. Due to the significant impact of CVD on humans, there is a need to
      develop novel treatment modalities tailored to major classes of cardiac diseases
      including hypertension, coronary artery disease, cardiomyopathies, arrhythmias,
      valvular disease and inflammatory diseases. In this article, we discuss recent
      advancements regarding development of therapeutic strategies based on stem cells,
      aptamers, exosomes, drug-eluting and dissolvable stents, immunotherapy and
      nanomedicine for the treatment of CVD. We summarize current research and clinical
      advances in cardiovascular therapeutics, with a focus on therapies that move
      beyond current oral- or sublingual-based regimens. This review article provides
      insight into current research and future treatment strategies that hold a great
      relevance for future clinical practice in pursuit of improving quality of life of
      patients suffering from CVD.

PMID- 29447003
TI  - A study on the genetic polymorphisms of CYP3A5 among the Orang Asli in Malaysia
      using a next generation sequencing platform.
AB  - BACKGROUND: CYP3A5 is the predominant sub-family of biotransformation enzymes in
      the liver and the genetic variations in CYP3A5 are an important determinant of
      inter-individual and inter-ethnic differences in CYP3A-mediated drug disposition
      and response. AIM: This study aims to investigate the genetic polymorphisms of
      CYP3A5 among the Orang Asli in Peninsular Malaysia using a next generation
      sequencing platform. METHODS: Genomic DNAs were extracted from blood samples of
      the three main Orang Asli tribes and whole-genome sequencing was performed.
      RESULTS: A total of 61 single nucleotide polymorphisms were identified and all
      the SNPs were located in introns except rs15524, which is in the 3'UTR, and 11 of
      these polymorphisms were novel. Two allelic variants and three genotypes were
      identified in the Orang Asli. The major allelic variant was the non-functional
      CYP3A5*3 (66.4%). The percentages of Orang Asli with CYP3A5*3/*3 (47.2%) and
      CYP3A5*1/*3 (38.1%) genotypes are more than twice the percentage of Orang Asli
      with CYP3A5*1/*1 (14.8%) genotype. Almost half of the Orang Asli harboured CYP3A5
      non-expressor genotype (CYP3A5*3/*3). CONCLUSIONS: The predominance of the CYP3A5
      non-expressor genotype among the Orang Asli was unravelled and the findings in
      this study may serve as a guide for the optimisation of pharmacotherapy for the
      Orang Asli community.

PMID- 29447004
TI  - Household food security, and social support as protective factors.

PMID- 29447005
TI  - Human ASIC1a mediates stronger acid-induced responses as compared with mouse
      ASIC1a.
AB  - Acid-sensing ion channels (ASICs) are the major proton receptor in the brain and
      a key mediator of acidosis-induced neuronal injuries in disease. Most of
      published data on ASIC function came from studies performed in mice, and
      relatively little is known about potential differences between human and mouse
      ASICs (hASIC and mASIC, respectively). This information is critical for us to
      better interpret the functional importance of ASICs in human disease. Here, we
      examined the expression of ASICs in acutely resected human cortical tissue.
      Compared with mouse cortex, human cortical tissue showed a similar ratio of
      ASIC1a:ASIC2a expression, had reduced ASIC2b level, and exhibited a higher
      membrane:total ratio of ASIC1a. We further investigated the mechanism for higher
      surface trafficking of hASIC1a in heterologous cells. A single amino acid at
      position 285 was critical for increased N-glycosylation and surface expression of
      hASIC1a. Consistent with the changes in trafficking and current, cells expressing
      hASIC1a or mASIC1a S285P mutant had a higher acid-activated calcium increase and
      exhibited worsened acidotoxicity. These data suggest that ASICs are likely to
      have a larger impact on acidosis-induced neuronal injuries in humans than mice,
      and this effect is, at least in part, a result of more efficient trafficking of
      hASIC1a.-Xu, Y., Jiang, Y.-Q., Li, C., He, M., Rusyniak, W. G., Annamdevula, N.,
      Ochoa, J., Leavesley, S. J., Xu, J., Rich, T. C., Lin, M. T., Zha, X.-M. Human
      ASIC1a mediates stronger acid-induced responses as compared with mouse ASIC1a.

PMID- 29447006
TI  - Retinoic acid signaling promotes the cytoskeletal rearrangement of embryonic
      epicardial cells.
AB  - All- trans-retinoic acid (RA), a vitamin A metabolite, is an important signaling
      molecule required for the proper development of the heart. The epicardium is the
      main source of RA in the embryonic heart, yet the cardiogenic functions of
      epicardial-produced RA are not fully understood. Here, we investigated the roles
      of RA signaling in the embryonic epicardium using in vivo and in vitro models of
      excess or deficiency of RA. Our results suggested that RA signaling facilitates
      the cytoskeletal rearrangement required for the epicardial-to-mesenchymal
      transition of epicardial cells. In vivo treatment with an inhibitor of RA
      synthesis delayed the migration of epicardial-derived precursor cells (EPDCs)
      into the myocardium; the opposite was seen in the case of dehydrogenase/reductase
      superfamily (DHRS)3-deficient embryos, a mouse model of RA excess. Analysis of
      the behavior of epicardial cells exposed to RA receptor agonists or inhibitors of
      RA synthesis in vitro revealed that appropriate levels of RA are important in
      orchestrating the platelet-derived growth factor-induced loss of epithelial
      character, cytoskeletal remodeling, and migration, necessary for the infiltration
      of the myocardium by EPDCs. To understand the molecular mechanisms by which RA
      regulates epicardial cytoskeletal rearrangement, we used a whole transcriptome
      profiling approach, which in combination with pull-down and inhibition assays,
      demonstrated that the Ras homolog gene family, member A (RhoA) pathway is
      required for the morphologic changes induced by RA in epicardial cells.
      Collectively, these data demonstrate that RA regulates the cytoskeletal
      rearrangement of epicardial cells via a signaling cascade that involves the RhoA
      pathway.-Wang, S., Yu, J., Jones, J. W., Pierzchalski, K., Kane, M. A., Trainor,
      P. A., Xavier-Neto, J., Moise, A. R. Retinoic acid signaling promotes the
      cytoskeletal rearrangement of embryonic epicardial cells.

PMID- 29447008
TI  - Extracellular HMGB1 as a therapeutic target in inflammatory diseases.
AB  - INTRODUCTION: High-mobility group box 1 (HMGB1) is a ubiquitous nuclear protein
      that promotes inflammation when released extracellularly after cellular
      activation, stress, damage or death. HMGB1 operates as one of the most intriguing
      molecules in inflammatory disorders via recently elucidated signal and molecular
      transport mechanisms. Treatments based on antagonists specifically targeting
      extracellular HMGB1 have generated encouraging results in a wide number of
      experimental models of infectious and sterile inflammation. Clinical studies are
      still to come. Areas covered: We here summarize recent advances regarding
      pathways for extracellular HMGB1 release, receptor usage, and functional
      consequences of post-translational modifications. The review also addresses
      results of preclinical HMGB1-targeted therapy studies in multiple inflammatory
      conditions and outlines the current status of emerging clinical HMGB1-specific
      antagonists. Expert opinion: Blocking excessive amounts of extracellular HMGB1,
      particularly the disulfide isoform, offers an attractive clinical opportunity to
      ameliorate systemic inflammatory diseases. Therapeutic interventions to regulate
      intracellular HMGB1 biology must still await a deeper understanding of
      intracellular HMGB1 functions. Future work is needed to create more robust assays
      to evaluate functional bioactivity of HMGB1 antagonists. Forthcoming clinical
      studies would also greatly benefit from a development of antibody-based assays to
      quantify HMGB1 redox isoforms, presently assessed by mass spectrometry methods.

PMID- 29447007
TI  - Valsartan attenuates bleomycin-induced pulmonary fibrosis by inhibition of NF
      kappaB expression and regulation of Th1/Th2 cytokines.
AB  - OBJECTIVE: Pulmonary fibrosis (PF) is a chronic respiratory system disease. The
      role of inflammation and angiotensin in the development and progression of PF has
      previously been demonstrated. Alternation in antifibrotic/profibrotic mediators
      and NF-kappaB activation have important roles in PF development. NF-kappaB, a
      nuclear factor, induces the transcription of inflammatory and pro-inflammatory
      cytokines. The aim of this study was to evaluate the effect of valsartan as an
      angiotensin receptor blocker on IL-4, INF-gamma, and NF-kappaB expression in the
      treatment of PF. MATERIALS AND METHODS: Rats were divided into five groups:
      groups I (bleomycin) and II (control) received a single injection of bleomycin
      (7.5 IU/kg) or vehicle, respectively. Groups III-V received valsartan (20, 40,
      and 80 mg/kg, respectively) orally a week before and for 3 weeks after the
      bleomycin injection. Serum levels of IL-4 and INF- gamma were then measured.
      Relative NF-kappaB expression was investigated by real-time PCR. RESULTS:
      Histopathological examination showed the anti-inflammation effect of valsartan.
      Bleomycin significantly increased IL-4 serum level and decreased that of INF
      gamma in the serum. Valsartan could restore their levels to normal. Valsartan
      raised the decreased ratio of INF-gamma/IL-4. Exposure to bleomycin elevated NF
      kappaB expression; and valsartan decreased the increased gene expression.
      DISCUSSION: Valsartan as an angiotensin receptor antagonist presumably by
      blocking angiotensin receptor causes to ameliorated PF, which was at least partly
      due to antifibrotic/profibrotic cytokine regulation and reduced NF-kappaB
      expression. CONCLUSIONS: Valsartan showed a significant protective effect against
      bleomycin-induced PF.

PMID- 29447009
TI  - Operation, hormone therapy and recovery of the patients with severe forms of
      adenomyosis.
AB  - Endometriosis is among the prevalent gynecological diseases and diagnosed in 10%
      of women of reproductive age. Endometriosis/adenomyosis is becoming increasingly
      a health-social problem, which is associated with severe clinical manifestations
      and recurrent disease which has a negative effect on quality of life, women
      ability to work and her reproductive function. This article presents modern
      approaches of drug therapy to treat severe forms of adenomyosis. We have reviewed
      recent major studies in the field of surgical treatment of this disease, analyzed
      the main stages of disease progress and the results of our surgeries. Here, we
      are presenting our own results of long-term post-operative hormonal therapy and
      complex medical treatment.

PMID- 29447010
TI  - Role of breast density measurement in screening for breast cancer.
AB  - Mammographic breast density is an established risk factor for breast cancer and
      significantly reduces the sensitivity of mammography, yet its use within breast
      cancer screening programs in Australia is limited. We provide a contemporary
      snapshot of the role of breast density measurement in screening for breast cancer
      and review the recent evidence for an increasing role of breast density
      measurement as: a predictor of breast cancer risk, a predictor of 'masking', and
      a biomarker to monitor effectiveness of intervention strategies for primary
      prevention or improved breast cancer outcomes.

PMID- 29447011
TI  - The genotoxic and antigenotoxic potential of the methanolic root extract of
      Glycyrrhiza glabra L. on human peripheral blood lymphocytes.
AB  - Glycyrrhiza glabra L. (licorice) is one of the most important medicinal plants,
      which is widely used throughout the world both in traditional and contemporary
      medical industries. This study was undertaken to investigate the potential
      genotoxic activity of G. glabra methanolic root extract, and its possible
      antigenotoxic properties against mitomycin C (MMC)-induced DNA damage in in vitro
      chromosome aberrations (CAs) and cytokinesis-block micronucleus (CBMN) assays in
      human peripheral blood lymphocytes (PBLs). Lymphocytes were treated with 25, 50,
      and 100 ug/ml G. glabra methanolic root extract alone as well as in combination
      with MMC (0.1 ug/ml) for 24 and 48 h treatment periods. It was found that there
      were no statistically significant differences between the negative control and
      the groups treated with all concentrations of G. glabra root extract of alone (p
      > 0.05), demonstrating the absence of genotoxic effects at both 24 and 48 h
      treatment periods. Besides, the co-treatment of G. glabra methanolic root extract
      and MMC significantly decreased the percentage of structural CAs and MN formation
      when compared with the culture treated with MMC alone (p < 0.001). In addition,
      the negative interaction factor (IF) values obtained for all combinations
      represent an antagonistic effect of G. glabra versus MMC. We can state that this
      extract acts as an antagonist and markedly decreased MMC-induced
      cytogenotoxicity. In conclusion, the present results demonstrate that in the
      tested experimental conditions, G. glabra methanolic root extract is not
      genotoxic in cultured human PBLs and has also antigenotoxic activity against MMC,
      which is widely used in chemotherapy against cancer.

PMID- 29447013
TI  - Identification of Three Types of alpha-Thalassemia Deletion, -alpha21.9, 
      alpha2.4, and - -THAI, and Their Frequencies, in One Family in the Population of
      Southern Guangxi Zhuang Autonomous Region, People's Republic of China.
AB  - Different types of deletional alpha-thalassemia (alpha-thal) have been reported
      by researchers in China. This study describes one family carrying -alpha21.9
      (NG_000006.1: g.14373_36299delinsGGGAAGGGTGGGTGGGAATAACAGCTTTT), -alpha2.4
      (NG_000006.1: g.36860_39251del) and - -THAI (Thailand) (NG_000006.1:
      g.10664_44164del) alleles in Guangxi Zhuang Autonomous Region, People's Republic
      of China (PRC), and reports the frequencies of these types in the population of
      this region. The proband was a 4-year-old girl, who screened positive for
      thalassemia, although the thalassemia genotype results were normal when screened
      using the routine kits. Samples of the proband's parents were also collected to
      perform further analyses. Two real-time gap-polymerase chain reaction (gap-PCR)
      systems were designed for separate detection of - -THAI and screening for 
      alpha21.9 and -alpha2.4. The genotype of the proband was -alpha21.9/-alpha2.4,
      and the two variants were inherited from her parents. In the frequency study,
      five - -THAI, four -alpha21.9 and 11 -alpha2.4 positive individuals were detected
      in the 3410 random samples. Thus, allele frequencies of -alpha21.9, - -THAI and 
      alpha2.4 in the population of southern Guangxi were determined as 0.059, 0.073
      and 0.161%, respectively. This is the first report of an individual carrying the 
      alpha21.9/-alpha2.4 genotype, and the first report of the detection of 
      alpha21.9, -alpha2.4 and - -THAI in a single family. The total frequency for
      these alleles was 0.293% in southern Guangxi, suggesting that the thalassemia
      clinical center in this region should utilize a screening kit that allows
      detection of these types of deletions for a more comprehensive evaluation of
      thalassemia risk.

PMID- 29447012
TI  - Structure-activity relationship investigation of tertiary amine derivatives of
      cinnamic acid as acetylcholinesterase and butyrylcholinesterase inhibitors:
      compared with that of phenylpropionic acid, sorbic acid and hexanoic acid.
AB  - In the present investigation, 48 new tertiary amine derivatives of cinnamic acid,
      phenylpropionic acid, sorbic acid and hexanoic acid (4d-6g, 10d-12g, 16d-18g and
      22d-24g) were designed, synthesized and evaluated for the effect on AChE and BChE
      in vitro. The results revealed that the alteration of aminoalkyl types and
      substituted positions markedly influences the effects in inhibiting AChE. Almost
      of all cinnamic acid derivatives had the most potent inhibitory activity than
      that of other acid derivatives with the same aminoalkyl side chain. Unsaturated
      bond and benzene ring in cinnamic acid scaffold seems important for the
      inhibitory activity against AChE. Among them, compound 6g revealed the most
      potent AChE inhibitory activity (IC50 value: 3.64 umol/L) and highest selectivity
      over BChE (ratio: 28.6). Enzyme kinetic study showed that it present a mixed-type
      inhibition against AChE. The molecular docking study suggested that it can bind
      with the catalytic site and peripheral site of AChE.

PMID- 29447014
TI  - Macrophage migration inhibitory factor (MIF) inhibitor, Z-590 suppresses
      cartilage destruction in adjuvant-induced arthritis via inhibition of macrophage
      inflammatory activation.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pleiotropic pro
      inflammatory mediator that is involved in the progression of rheumatoid arthritis
      (RA). Previously, we demonstrated a small molecule compound 3-[(biphenyl-4
      ylcarbonyl) carbamothioyl] amino benzoic acid (Z-590) could inhibit MIF activity
      with docking-based virtual screening and experimental evaluation. METHODS: The
      LPS activated RAW264.7 macrophage cells were used to determine the anti
      inflammatory effects of Z-590 in vitro. A rat adjuvant-induced arthritis (AIA)
      model was used to determine the anti-arthritic effects of Z-590 in vivo. RESULTS:
      MIF inhibitor Z-590 significantly inhibited the production of NO, TNF-alpha and
      IL-6 in LPS-activated RAW 264.7 macrophage cells and markedly inhibited LPS
      induced expression of TNF-alpha, IL-6, inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2). Z-590 also significantly reduced paw edema, serum level
      of TNF-alpha, IL-6 and spleen index in the adjuvant-induced arthritis (AIA) rat
      model. Furthermore, Z-590 markedly ameliorated joint inflammation and articular
      cartilage damage in AIA rat model. CONCLUSION: MIF inhibitor Z-590 possesses
      potent anti-arthritic activity through suppression of macrophage activation, and
      could be a potential therapeutic treatment for RA.

PMID- 29447015
TI  - Optogenetics in cancer drug discovery.
AB  - INTRODUCTION: The discovery and domestication of biomolecules that respond to
      light has taken a light of its own, providing new molecular tools with incredible
      spatio-temporal resolution to manipulate cellular behavior. Areas covered: The
      authors herein analyze the current optogenetic tools in light of their current,
      and potential, uses in cancer drug discovery, biosafety and cancer biology.
      Expert opinion: The pipeline from drug discovery to the clinic is plagued with
      drawbacks, where most drugs fail in either efficacy or safety. These issues
      require the redesign of the pipeline and the development of more
      controllable/personalized therapies. Light is, aside from inexpensive, almost
      harmless if used appropriately, can be directed to single cells or organs with
      controllable penetration, and comes in a variety of wavelengths. Light-responsive
      systems can activate, inhibit or compensate cell signaling pathways or specific
      cellular events, allowing the specific control of the genome and epigenome, and
      modulate cell fate and transformation. These synthetic molecular tools have the
      potential to revolutionize drug discovery and cancer research.

PMID- 29447017
TI  - A data-based hypothesis explicating the observations that "Smoking is associated
      with risk for developing inflammatory bowel disease including late onset
      ulcerative colitis: a prospective study".

PMID- 29447016
TI  - TGF-b1 or hypoxia enhance glucose metabolism and lactate production via HIF1A
      signaling in tendon cells.
AB  - : Purpose/Aim of the study: Healthy tendons are maintained in homeostasis through
      controlled usage of glucose for energy and redox equilibrium. Tendon cell stress
      imposed by overuse injury or vascular insufficiency is accompanied by activation
      of wound healing pathways which facilitate an adaptive response and the
      restoration of homeostasis. To understand this response at the gene expression
      level we have studied the in vivo effects of injected TGF-beta1 in a murine model
      of tendinopathy, as well as treatment of murine tendon explants with either TGF
      beta1 or hypoxia in vitro. METHODS AND RESULTS: We provide evidence (from
      expression patterns and immunohistochemistry) that both in vivo and in vitro, the
      stress response in tendon cells may be metabolically controlled in part by
      glycolytic reprogramming. A major feature of the response to TGF-beta1 or hypoxia
      is activation of the Warburg pathway which generates lactate from glucose under
      normoxia and thereby inhibits mitochondrial energy production. CONCLUSIONS: We
      discuss the likely outcome of this major metabolic shift in terms of the
      potential benefits and damage to tendon and suggest how incorporation of this
      metabolic response into our understanding of initiation and progression of
      tendinopathies may offer new opportunities for diagnosis and the monitoring of
      therapies.

PMID- 29447018
TI  - Summary of numerical analyses for therapeutic uses of laser-activated gold
      nanoparticles.
AB  - The optimal light dose, heat generation, consequent heat spread and an accurate
      thermal damage model, are key components of effective laser therapies. Recent
      advances in nanotechnology offer numerous possibilities on how to increase the
      efficacy of hyperthermia for tumour treatments. Gold nanoparticles are a
      promising candidate towards the achievement of this goal owing to their
      properties for efficiently converting light to heat. In this review, we summarise
      the numerical tools that are available for theoretical studies of gold
      nanoparticle-mediated photo-thermal therapy. The processes that occur in the
      treatments based on light propagation inside biological tissues and the
      subsequent temperature distributions are considered first, followed by evaluation
      of the thermal damage. The fundamental ideas underlying the presented methods are
      described in addition to their applications in photo-thermal therapy and its
      effects. The descriptions of extensively used tools for the characterisation of
      nanoparticles across multiple research fields are also presented for estimating
      the electromagnetic properties of gold nanoparticles (e.g. discrete dipole
      approximations, finite-difference time-domain simulations), the Monte Carlo model
      of light propagation in biological tissues, and the Pennes' bio-heat equation. In
      addition, the Arrhenius damage evaluation and the cumulative effective minutes
      normalisation methods are described. Finally, recent in vivo and in vitro results
      from the rapidly growing field of nanomedicine are presented.

PMID- 29447019
TI  - Lysophosphatidic acid enhanced the osteogenic and angiogenic capability of
      osteoblasts via LPA1/3 receptor.
AB  - Lysophosphatidic acid is a serum-derived growth factor that is involved in wound
      healing. Although in its infancy, a growing body of evidence has demonstrated
      that lysophosphatidic acid exerts a potentially significant role in regulating
      bone cell biology. However, previous studies mainly focused on the osteoinductive
      potential of lysophosphatidic acid, its effects on bone tissue vascularization,
      another essential element during bone regeneration, remains ill-defined so far.
      Here in this study, we examined the effects of lysophosphatidic acid on
      osteogenic differentiation as well as the angiogenesis-inducing capacity of pre
      osteoblasts, a cell population that coordinates osteogenic and angiogenic
      processes in bone regenerating niche. Our results showed that treatment of MC3T3
      E1 pre-osteoblastic cells with lysophosphatidic acid enhanced alkaline
      phosphatase activity and matrix mineralization, demonstrating in vitro
      osteoblastic differentiation. Of particular importance was the finding that
      vascular endothelial growth factor secretion also increased after
      lysophosphatidic acid treatment. Lysophosphatidic acid conditioned media of MC3T3
      E1 cells was capable of promoting angiogenic behavior of endothelial cells, as
      evidenced by stimulating proliferation, migration, and tube formation. Besides,
      inhibition of LPA1/3 receptor abolished lysophosphatidic acid-induced elevation
      of the osteogenic and angiogenic capability of pre-osteoblasts. Our research
      demonstrated the important role of lysophosphatidic acid in coupling osteogenesis
      and angiogenesis during bone remodeling through orchestrating pre-osteoblast
      behavior, and implications therein for novel and effective treatment strategies
      for bone regeneration success.

PMID- 29447020
TI  - Effect of pre-treatment with gonadotropin-releasing hormone analogue GnRH-alpha
      on high-intensity focussed ultrasound ablation for diffuse adenomyosis: a
      preliminary study.
AB  - OBJECTIVES: To evaluate the efficacy and safety of GnRH-alpha pre-treatment with
      HIFU ablation for diffuse adenomyosis. METHODS: From January 2014 to December
      2016, 61 patients were divided into two groups. Twenty-three patients with larger
      uteri received pre-treatment with GnRH-alpha and were then subjected to HIFU, and
      38 patients underwent HIFU alone. The technical parameters included treatment
      time, sonication time, average sonication power, treatment intensity, total
      energy, non-perfusion volume (NPV) and NPV ratio. Intra-, post-procedural
      complaints, the relief rate of dysmenorrhoea and clinical effectiveness were
      followed up. RESULTS: Although the lesion volume in the HIFU + GnRH group was
      larger than in the HIFU-only group, higher NPV, NPVR%, treatment intensity and
      total energy with shorter treatment and sonication times in the HIFU + GnRH group
      were obtained than that in the HIFU-only group. Significant differences were
      evident for NPV, NPVR%, average power, and total intensity energy (p < 0.05), but
      not for other parameters between the two groups (p > 0.05). Although no
      differences in the intra-, post-procedural VAS scores, in the adverse effects and
      in the relief rate or clinical effectiveness were apparent between the two groups
      (p > 0.05), the relief rate was better in the HIFU + GnRH group than that in the
      HIFU group from 6 to 12 months after treatment. Self-comparison of differences
      occurred in the two groups before and after treatment (p < 0.05) and were between
      the two groups after only 6 months (p < 0.05). CONCLUSION: The combination of
      HIFU with GnRH-alpha is more effective than HIFU alone for ablation of diffuse
      adenomyosis. Moreover, the GnRH-alpha pre-treatment with HIFU is safe.

PMID- 29447022
TI  - Correction to: Seyyed Abootorabi et al., The effect of vitamin D supplementation
      on insulin resistance, visceral fat and adiponectin in vitamin D deficient women
      with polycystic ovary syndrome: a randomized placebo-controlled trial.

PMID- 29447023
TI  - Designing a Low-Cost, Single-Supply ECG System for Suppression of Movement
      Artifact from Contaminated Magnetocardiogram.
AB  - Measurement of the late potentials and His-bundle activity is crucial for many
      clinical studies using the noncontact and noninvasive magnetocardiography (MCG)
      technique; these weak signals are extracted by averaging many cardiac cycles
      aligned using the R-peak of the cardiac cycle identified using an
      electrocardiography (ECG) lead. ECG is measured simultaneously with MCG using a
      conventional dual-supply ECG amplifier, which requires either two separate
      batteries or a single battery with a switching voltage inverter circuit for its
      proper operation. The ECG circuitry based on two separate batteries requires a
      relatively large voltage supply (-18 to +18 V). The single-supply (low voltage: 0
      9 V) ECG circuitry may be implemented using a switching voltage inverter;
      however, this mode of operation introduces switching noise in the system. The
      objective of the present work is to overcome these problems by carefully
      designing a low-voltage, single-supply ECG system, which can be used
      simultaneously with the MCG setup without introducing a significant level of
      additional noise in the MCG measurement system.

PMID- 29447024
TI  - Microbiology and clinical outcomes of puerperal sepsis: a prospective cohort
      study.
AB  - The objectives of this study were to determine the identity and antibacterial
      susceptibility profiles of bacteria colonising the female genital tract and blood
      stream and their association with clinical outcomes in women with puerperal
      sepsis. A prospective descriptive cohort study was conducted at two tertiary
      hospitals in Zimbabwe. Endocervical swabs and blood were collected for culture
      and susceptibility testing from 151 consecutive women who met the World Health
      Organisation criteria for puerperal sepsis. Medical records were reviewed for
      assessment of clinical outcomes. The commonest bacterial isolates were
      Escherichia coli (30.6%) and Klebsiella pneumoniae (15.3%). Multidrug-resistant
      organisms (MDRO) accounted for 10.9% of all isolates. MDRO were associated with
      prolonged hospital stay, 23.0 days compared to 10.5 days in women without MDRO (p
      = .009). Puerperal sepsis case fatality rate was 7.3%. Clinical culture
      surveillance to monitor epidemiologic trends, identify MDRO, robust infection
      control strategies and emphasis on rational drug use are recommended. Impact
      statement What is already known? Puerperal sepsis is often a polymicrobial
      infection. Escherichia coli has been reported as a common cause of severe
      maternal sepsis originating from the genital tract. Other bacteria include Group
      A Streptococcus, S. aureus, Streptococcus spp. Klebsiellae spp, Pseudomonas spp.
      and anaerobes. What does this study add? This study confirms Escherichia coli as
      the commonest cause of sepsis in Harare. There is high level resistance to first
      line antibiotic regimens on most Gram-negative isolates from the endocervix among
      women with puerperal sepsis. Emerging resistance to carbapenems is demonstrated.
      MDRO significantly increased length of hospital stay, and there was a clinically
      important trend towards higher rates of pelvic abscess, septic shock, death, need
      for laparotomy and ICU admission specific to puerperal sepsis. What are the
      implications for clinical practice and further research? Clinical culture
      surveillance to monitor epidemiologic trends in conjunction with robust infection
      control strategies and rational drug use may assist in prevention of community
      acquired and nosocomial multidrug-resistant infections.

PMID- 29447021
TI  - Release of pro-inflammatory cytokines from muscle and bone causes tenocyte death
      in a novel rotator cuff in vitro explant culture model.
AB  - PURPOSE: Tendinopathy is a significant clinical problem thought to be associated
      with altered mechanical loading. Explant culture models allow researchers to
      alter mechanical loading in a controlled in vitro environment while maintaining
      tenocytes in their native matrix. However, current models do not accurately
      represent commonly injured tendons, ignoring contributions of associated
      musculature and bone, as well as regional collagen structure. This study details
      the characterization of amouse rotator cuff explant culture model, including
      bone, tendon, and muscle (BTM). MATERIALS AND METHODS: Following harvest, BTM
      explants were maintained in stress-deprived culture for one week and tendon was
      then assessed for changes in cell viability, metabolism, matrix structure and
      content. RESULTS: Matrix turnover occurred throughout culture as manifested in
      both gene expression and biosynthesis, but this did not translate to net changes
      in total collagen or sulfated glycosaminoglycan content. Furthermore, tendon
      structure was not significantly altered throughout culture. However, we found
      significant cell death in BTM tendons after 3 days in culture, which we
      hypothesize is cytokine-induced. Using a targeted multiplex assay, we found high
      levels of pro-inflammatory cytokines released to the culture medium from muscle
      and bone, levels that did cause cell deathin tendon-alone controls. CONCLUSIONS:
      Overall, this model presents an innovative approach to understandingrotator cuff
      injury and tenocyte mechanobiology in a clinically-relevant tendon structure. Our
      model can be a powerful tool to investigate how mechanical and biological stimuli
      can alter normal tendon health and lead to tendon degeneration, and may provide a
      testbed for therapeutics for tendon repair.

PMID- 29447025
TI  - Anal sphincter dysfunction in patients treated with primary radiotherapy for anal
      cancer: a study with the functional lumen imaging probe.
AB  - BACKGROUND: Sphincter-sparing radiotherapy or chemoradiation are standard
      treatments for patients with anal cancer. The ultimate treatment goal is full
      recovery from anal cancer with preserved anorectal function. Unfortunately, long
      term survivors often suffer from severe anorectal symptoms. The aim of the
      present study was to characterize changes in anorectal physiology after
      radiotherapy for anal cancer. METHOD: We included 13 patients (10 women, age 63.4
      +/- 1.9) treated with radiotherapy or chemoradiation for anal cancer and 14
      healthy volunteers (9 women, age 61.4 +/- 1.5). Symptoms were assessed with
      scores for fecal incontinence and low anterior resection syndrome. Anorectal
      physiology was examined with anorectal manometry and the Functional Lumen Imaging
      Probe. RESULTS: Patients had a median Wexner fecal incontinence score of 5 (0-13)
      and a median LARS score of 29 (0-39). Compared to healthy volunteers, patients
      had lower mean (+/-SE) anal -resting (38 +/- 5 vs. 71 +/- 6, p < .001) and 
      squeeze pressures (76 +/- 11 vs. 165 +/- 15, p < .001). Patients also had lower
      anal yield pressure (15.5 +/- 1.3 mmHg vs. 28.0 +/- 2.0 mmHg, p < .001), higher
      distensibility, and lower resistance to flow (reduced resistance ratio of the
      anal canal during distension, q = 5.09, p < .001). No differences were found in
      median (range) rectal volumes at first sensation (70.5 (15-131) vs. 57 (18-132)
      ml, p > .4), urge (103 (54-176) vs. 90 (32-212), p > .6) or maximum tolerable
      volume (173 (86-413) vs. 119.5 (54-269) ml, p > .10). CONCLUSION: Patients
      treated with radiotherapy or chemoradiation for anal cancer have low anal resting
      and squeeze pressures as well as reduced resistance to distension and flow.

PMID- 29447026
TI  - The importance of cluster analysis for enhancing clinical practice: an example
      from irritable bowel syndrome.

PMID- 29447027
TI  - Current knowledge of transient hypothyroxinemia of prematurity: to treat or not
      to treat?
AB  - BACKGROUND: Thyroid hormones (THs) play a critical role in normal maturation of
      the developing brain in the fetus and infant. Continuing advances in neonatal
      medicine have contributed to an increased survival of extremely premature infants
      with neonatal morbidities. In these infants, thyroid system immaturities, as well
      as morbidity-related thyroid dysfunction, contribute to transient
      hypothyroxinemia of prematurity (THOP), which is characterized by very low total
      and free thyroxine and normal or low thyroid-stimulating hormone (TSH) levels.
      REVIEW: Undoubtedly, low levels of THs with elevated TSH are associated with poor
      neurodevelopmental outcome. However, continuing debate exists regarding whether
      THOP is harmful to the developing brain. Moreover, no clear effects of TH
      treatment on neurodevelopmental outcome in preterm infants with THOP have been
      demonstrated. THs could have unpredictable effects if given unnecessarily.
      CONCLUSION: The current recommendation is to treat THOP with TH only if THOP is
      accompanied with TSH elevation.

PMID- 29447028
TI  - Elastase as a potential biomarker for radiation-induced gut wall injury of the
      distal bowel in an experimental mouse model.
AB  - BACKGROUND AND PURPOSE: Traditionally, elastase has been used to study exocrine
      activity of the pancreas in patients with chronic pancreatitis and cystic
      fibrosis, and calprotectin as a marker for gut-wall inflammation in patients with
      inflammatory bowel disease. The aim of the study was to find out whether elastase
      and calprotectin could be used as inflammatory markers for radiation-induced gut
      wall injury of the distal bowel. MATERIAL AND METHODS: Adult male mice were
      exposed to two, three, or four fractions of 6 Gy or 8 Gy irradiation to the
      sigmoid and rectum of the large bowel, using a linear accelerator. Fecal samples
      were collected from mice at 1, 3, and 6 weeks post-irradiation. The fecal levels
      of elastase and calprotectin were analyzed using ELISA. RESULTS: Three and 6
      weeks after irradiation, we found a dose-effect relationship between dose of
      ionizing radiation and the fecal level of elastase; that is significantly higher
      levels of elastase were observed in mice that had received a high irradiation
      dose. We also found that irradiated mice hosted in the same cage had a comparable
      level (either high or low) of elastase. No significant differences were observed
      from the calprotectin data. CONCLUSIONS: We found a clear association between the
      dose of ionizing radiation to the distal colon and the level of elastase in the
      fecal samples.

PMID- 29447030
TI  - The Interview: Make It Work for You.

PMID- 29447029
TI  - Nanosilver and the microbiological activity of the particulate solids versus the
      leached soluble silver.
AB  - Nanosilver (Ag NPs) is currently one of the most commercialized antimicrobial
      nanoparticles with as yet, still unresolved cytotoxicity origins. To date,
      research efforts have mostly described the antimicrobial contribution from the
      leaching of soluble silver, while the undissolved solid Ag particulates are often
      considered as being microbiologically inert, serving only as source of the
      cytotoxic Ag ions. Here, we show the rapid stimulation of lethal cellular
      oxidative stress in bacteria by the presence of the undissolved Ag particulates.
      The cytotoxicity characteristics are distinct from those arising from the leached
      soluble Ag, the latter being locked in organic complexes. The work also
      highlights the unique oxidative stress-independent bacterial toxicity of silver
      salt. Taken together, the findings advocate that future enquiries on the
      antimicrobial potency and also importantly, the environmental and clinical impact
      of Ag NPs use, should pay attention to the potential bacterial toxicological
      responses to the undissolved Ag particulates, rather than just to the leaching of
      soluble silver. The findings also put into question the common use of silver salt
      as model material for evaluating bacterial toxicity of Ag NPs.

PMID- 29447031
TI  - Patient-Physician E-Mail.

PMID- 29447032
TI  - ASCO Clinical Practice Guideline for the Use of Larynx-Preservation Strategies in
      the Treatment of Laryngeal Cancer: Guideline Summary.

PMID- 29447034
TI  - House Committees Hold Hearings on Medicare Payments, Quality Care, and Pay for
      Performance.

PMID- 29447033
TI  - Reimbursement for Preventive Counseling Services.

PMID- 29447035
TI  - Erratum.

PMID- 29447037
TI  - Hiring Employees: Getting the Process Right.

PMID- 29447036
TI  - Byte Back.

PMID- 29447038
TI  - Weekly PLWC Feature Articles.

PMID- 29447039
TI  - Antitrust Law Focus of Second Annual State Society Meeting.

PMID- 29447041
TI  - Do You Have Up-to-Date Coding Books?

PMID- 29447040
TI  - ASCO Advocacy for Coverage of Off-Label Oncology Drug Uses.

PMID- 29447042
TI  - Facilitating a Global Cancer Dialogue.

PMID- 29447043
TI  - Re-engineering the interpretation of electronic fetal monitoring to identify
      reversible risk for cerebral palsy: a case control series.
AB  - BACKGROUND: Even key opinion leaders now concede that electronic fetal monitoring
      (EFM) cannot reliably identify fetal acidemia which many vouch as the only labor
      mediated pathophysiologic precursor for cerebral palsy (CP). We have developed
      the "Fetal Reserve Index" - an algorithm combining five dynamic components of EFM
      (1. Rate, 2. Variability, 3. Accelerations, 4. Decelerations, and 5. Excessive
      uterine activity) considered individually that are combined with the presence of:
      6. maternal, 7. obstetrical, and 8. fetal risk factors. OBJECTIVE: Here, we
      compare this 8-point fetal reserve index (FRI) against the performance of ACOG
      monograph criteria and ACOG Category systems for predicting risk for both CP and
      the need for emergency operative delivery (EOD). We then studied how varied
      management for screen positives (Red zone-defined below) impacts the outcome of
      such cases. STUDY DESIGN: Four hundred twenty term patients were studied: all
      entered labor with normal EFMs and no apparent cause of harm except events of
      labor and delivery. Sixty subsequently developed CP, and 360 were apparently
      normal controls. An FRI, normal on all eight parameters scored 100%, 4 of the 8
      was 50%, etc. We divided cases into Green zone >50%, Yellow 50-26%, and Red
      <=25%. An FRI in the Red zone was considered a positive screen. We then compared
      performance metrics for the three evaluation schemes and differences between
      controls that reached Red against those controls whose worst scores were
      Green/Yellow. RESULTS: For detection of injury during labor, the FRI performed
      much better than the ACOG Category criteria (sensitivity 28%), and Category III
      (45%) (p < .001). All CP cases reached Red zone and were Red for a minimum of 2
      hours (mean = 5.35 hours). Twenty-four% of controls reached Red, but were only
      Red for average of 1 hr. The incidence of low Apgar's, pH, FRI, and Lowest FRI
      increased progressively from Green/Yellow controls to red controls to CP cases.
      Irrespective, CP cases met ACOG Monograph criteria for labor injury less than 50%
      of the time. Only half of CP babies had umbilical artery pH values <7.00, and
      less than 50% showed Category III patterns. The earlier in labor the Red zone was
      reached, the more likely for a baby to develop CP or the mother to require an EOD
      regardless of fetal outcome. Successful intrauterine resuscitations (IR)
      diminished time spent in the Red zone and the need for EODs. CONCLUSIONS: FRI
      shows better discrimination for adverse fetal outcome and EOD than traditional
      EFM interpretation. The Category system is a very poor, subjective screening
      method as the vast majority of CP babies never reach the "action point" result of
      Category III. While reaching the Red zone does not ordain a bad outcome, how it
      is managed, does. Compared to CP cases, Red controls were delivered faster, had
      higher FRIs, and often had prompt management including IR maneuvers, which
      improved the FRI and lowered the risk of EODs even for cases with normal
      outcomes. With further study and validation, the quantitative FRI approach may
      replace the current, very subjective interpretation with a quantitative "lab
      test" approach.

PMID- 29447044
TI  - Improving the health of mental health staff through exercise interventions: a
      systematic review.
AB  - BACKGROUND: Exercise interventions are efficacious in reducing cardiometabolic
      risk and improving symptoms in people with severe mental illness, yet evidence
      guiding the implementation and scalability of such efforts is lacking. Given
      increasing efforts to address the disparity in physical health outcomes facing
      people with a mental illness, novel approaches to increasing adoption of
      effective interventions are required. Exercise interventions targeting mental
      health staff may improve staff health while also creating more positive attitudes
      towards the role of lifestyle interventions for people experiencing mental
      illness. AIMS: We aimed to determine the feasibility, acceptability and
      effectiveness of exercise interventions delivered to staff working in mental
      health services. METHOD: A systematic review was conducted from database
      inception, until November 2017. Studies recruiting staff participants to receive
      an exercise intervention were eligible for inclusion. RESULTS: Five studies met
      the inclusion criteria. Physical health interventions for mental health staff
      were feasible and acceptable with low dropout rates. Reductions in anthropometric
      measures and work-related stress were reported. CONCLUSIONS: Limited evidence
      suggests that exercise interventions targeting mental health staff are feasible
      and acceptable. Further research is required to determine the efficacy of such
      interventions and the impact such strategies may have on staff culture and
      patient outcomes.

PMID- 29447045
TI  - A Four-Channel Electrical Impedance Spectroscopy Module for Cortisol Biosensing
      in Sweat-Based Wearable Applications.
AB  - A four-channel electrochemical impedance spectroscopy (EIS) analyzer module has
      been demonstrated on flexible chemi-impedance sensors fabricated with gold
      electrodes for wearable applications. The module can perform time division
      multiplexed (TDM) impedance measurements on four sensors at 1 kHz. In this work,
      we characterize the system for the detection of cortisol in an ultralow volume (1
      3 uL) of perspired human sweat, sensor performance, and effects during continuous
      cortisol dosing and with pH and temperature variations expected on the surface of
      the skin that would be representative of use conditions as seen by a wearable
      device. Detection of cortisol was shown for concentrations of 1 pg/mL to 200
      ng/mL in both synthetic and perspired human sweat, and output response reported
      as a change in impedance with varying cortisol concentrations. Continuous dose
      testing was performed to demonstrate the stability of the sensors over prolonged
      periods of operation for cortisol concentrations within the physiologically
      relevant range of 10-200 ng/mL reported in human sweat. Temperature and pH
      effects testing was performed for pH range 4-8 and in a temperature chamber for
      the clinical range reported on the surface of human skin: 25-40  degrees C. The
      cortisol sensor demonstrated stability of operation with 7.58% variability under
      these conditions.

PMID- 29447048
TI  - Social media, cyber-aggression and student mental health on a university campus.
AB  - AIM: Information and communication technologies (ICTs) offer immense benefits for
      university students including enhancing engagement and connections with others
      and promoting self-directed and interactive learning. Perceived anonymity and the
      absence of social cues, however, may contribute to risk of interpersonal
      aggression. While extensive research examines bullying in child and adolescent
      educational settings, this study addresses a gap regarding post-secondary
      environments. METHODS: An internet-based survey was provided to 5004 university
      students to examine the nature, extent and consequences of cyber-aggression. The
      survey received a response from 1350 students, a response rate of 28.5%. To
      enable further exploration, nine focus groups and eight individual interviews
      were conducted. RESULTS: This exploratory study found one quarter of respondents
      had a private video or photo shared without their permission and 28% were sent
      angry, vulgar, threatening or intimating messages. Perpetrators were most likely
      to be a friend (50%), another student (20%) or an intimate partner (18%). Focus
      group data revealed risks of ICTs and the need for resources and support to
      address students' wellbeing in the context of cyber-aggression. CONCLUSION: Cyber
      aggression is experienced by a significant minority of university students,
      impacting their sense of wellbeing and mental health.

PMID- 29447047
TI  - Prospective comparative study of 18F-sodium fluoride PET/CT and planar bone
      scintigraphy for treatment response assessment of bone metastases in patients
      with prostate cancer.
AB  - AIM: To compare 18F-sodium fluoride positron emission tomography/computed
      tomography (NaF PET/CT) and 99mTc-labelled diphosphonate bone scan (BS) for the
      monitoring of bone metastases in patients with prostate cancer undergoing anti
      cancer treatment. MATERIAL AND METHODS: Data from 64 patients with prostate
      cancer were included. The patients received androgen-deprivation therapy (ADT),
      next-generation hormonal therapy (NGH) or chemotherapy. The patients had a
      baseline scan and 1-3 subsequent scans during six months of treatment. Images
      were evaluated by experienced nuclear medicine physicians and classified for
      progressive disease (PD) or non-PD according to the Prostate Cancer Working Group
      2 (PCWG-2) criteria. The patients were also classified as having PD/non-PD
      according to the clinical and prostate-specific antigen (PSA) responses. RESULTS:
      There was no difference between NaF PET/CT and BS in the detection of PD and non
      PD during treatment (McNemar's test, p = .18). The agreement between BS and NaF
      PET/CT for PD/non-PD was moderate (Cohen's kappa 0.53, 95% confidence interval
      0.26-0.79). Crude agreement between BS and NaF PET/CT for the assessment of
      PD/non-PD was 86% (89% for ADT, n = 28; 88% for NGH, n = 16, and 80% for
      chemotherapy, n = 20). In most discordant cases, BS found PD when NaF PET/CT did
      not, or BS detected PD on an earlier scan than NaF PET/CT. Biochemical
      progression (27%) occurred more frequently than progression on functional imaging
      (BS, 22% and NaF PET/CT, 14%). Clinical progression was rare (11%), and almost
      exclusively seen in patients receiving chemotherapy. CONCLUSION: There was no
      difference between NaF PET/CT and BS in the detection of PD and non-PD; however,
      BS seemingly detects PD by the PCWG-2 criteria earlier than NaF-PET, which might
      be explained by the fact that NaF-PET is more sensitive at the baseline scan.

PMID- 29447046
TI  - Oral curcumin supplementation improves fine motor function in the middle-aged
      rhesus monkey.
AB  - Aged individuals experience decreased fine motor function of the hand and digits,
      which could result, in part, from the chronic, systemic state of inflammation
      that occurs with aging. Recent research for treating age-related inflammation has
      focused on the effects of nutraceuticals that have anti-inflammatory properties.
      One particular dietary polyphenol, curcumin, the principal curcuminoid of the
      spice turmeric, has been shown to have significant anti-inflammatory effects and
      there is mounting evidence that curcumin may serve to reduce systemic
      inflammation. Therefore, it could be useful for alleviating age-related
      impairments in fine motor function. To test this hypothesis we assessed the
      efficacy of a dietary intervention with a commercially available optimized
      curcumin to ameliorate or delay the effects of aging on fine motor function of
      the hand of rhesus monkeys. We administered oral daily doses of curcumin or a
      control vehicle to 11 monkeys over a 14- to 18-month period in which they
      completed two rounds of fine motor function testing. The monkeys receiving
      curcumin were significantly faster at retrieving a food reward by round 2 of
      testing than monkeys receiving a control vehicle. Further, the monkeys receiving
      curcumin demonstrated a greater degree of improvement in performance on our fine
      motor task by round 2 of testing than monkeys receiving a control vehicle. These
      findings reveal that fine motor function of the hand and digits is improved in
      middle-aged monkeys receiving chronic daily administration of curcumin.

PMID- 29447049
TI  - Impact of acute and subchronic inhalation exposure to PbO nanoparticles on mice.
AB  - Lead nanoparticles (NPs) are released into air from metal processing, road
      transport or combustion processes. Inhalation exposure is therefore very likely
      to occur. However, even though the effects of bulk lead are well known, there is
      limited knowledge regarding impact of Pb NPs inhalation. This study focused on
      acute and subchronic exposures to lead oxide nanoparticles (PbO NPs). Mice were
      exposed to PbO NPs in whole body inhalation chambers for 4-72 h in acute
      experiment (4.05 * 106 PbO NPs/cm3), and for 1-11 weeks in subchronic experiment
      (3.83 * 105 particles/cm3 in lower and 1.93 * 106 particles/cm3 in higher
      exposure group). Presence of NPs was confirmed in all studied organs, including
      brain, which is very important considering lead neurotoxicity. Lead concentration
      gradually increased in all tissues depending on the exposure concentration and
      duration. The most burdened organs were lung and kidney, however liver and brain
      also showed significant increase of lead concentration during exposure.
      Histological analysis documented numerous morphological alterations and tissue
      damage, mainly in lung, but also in liver. Mild pathological changes were
      observed also in kidney and brain. Levels of glutathione (reduced and oxidized)
      were modulated mainly in lung in both, acute and subchronic exposures. Increase
      of lipid peroxidation was observed in kidney after acute exposure. This study
      characterized impacts of short to longer-term inhalation exposure, proved
      transport of PbO NPs to secondary organs, documented time and concentration
      dependent gradual increase of Pb concentration and histopathological damage in
      tissues.

PMID- 29447050
TI  - Added value of cerebro-placental ratio and uterine artery Doppler at routine
      third trimester screening as a predictor of SGA and FGR in non-selected
      pregnancies.
AB  - OBJECTIVES: The objective of this study is to determine the added value of
      cerebroplacental ratio (CPR) and uterine Doppler velocimetry at third trimester
      scan in an unselected obstetric population to predict smallness and growth
      restriction. METHODS: We constructed a prospective cohort study of women with
      singleton pregnancies attended for routine third trimester screening (32+0-34+6
      weeks). Fetal biometry and fetal-maternal Doppler ultrasound examinations were
      performed by certified sonographers. The CPR was calculated as a ratio of the
      middle cerebral artery to the umbilical artery pulsatility indices. Both
      attending professionals and patients were blinded to the results, except in cases
      of estimated fetal weight < p10. The association between third trimester Doppler
      parameters and small for gestational age (SGA) (birth weight <10th centile) and
      fetal growth restriction (FGR) (birth weight below the third centile) was
      assessed by logistic regression, where the basal comparison was a model
      comprising maternal characteristics and estimated fetal weight (EFW). RESULTS: A
      total of 1030 pregnancies were included. The mean gestational age at scan was 33
      weeks (SD 0.6). The addition of CPR and uterine Doppler to maternal
      characteristics plus EFW improved the explained uncertainty of the predicting
      models for SGA (15 versus 10%, p < .001) and FGR (12 versus 8%, p = .03).
      However, the addition of CPR and uterine Doppler to maternal characteristics plus
      EFW only marginally improved the detection rates for SGA (38 versus 34% for a 10%
      of false positives) and did not change the predictive performance for FGR.
      CONCLUSIONS: The added value of CPR and uterine Doppler at 33 weeks of gestation
      for detecting defective growth is poor.

PMID- 29447051
TI  - Targeting crosstalk between Nuclear factor (erythroid-derived 2)-like 2 and
      Nuclear factor kappa beta pathway by Nrf2 activator dimethyl fumarate in
      epileptogenesis.
AB  - : Purpose/Aim: Epilepsy is a complex, chronic neurological disorder characterized
      by increased and abnormal synchronization of neuronal electrical activity, which
      is manifested as seizures. It is associated with many comorbid conditions such as
      depression, anxiety, sleep disorder, psychiatric disorder etc., which
      consequently causes higher mortality rate. The understanding of its cellular and
      molecular mechanism is partial, because of which it remains an ongoing health
      problem, despite the increasing availability of newer antiepileptic drugs.
      Although recurrent seizures are the clinical indication of epilepsy, the disease
      process (epileptogenesis) begins before the onset of the first seizure. This
      dormant phase before the onset of first seizure provides an opportune time window
      for modifying the epileptogenic process by intervening in its progression with an
      appropriate treatment. MATERIAL AND METHODS: Studies have shown that in epilepsy,
      there is a chronic state of oxidative stress and inflammation, which plays a key
      role in epileptic pathogenesis. Various antioxidant mechanisms maintain the redox
      balance in the body by either scavenging or regulating the generation of free
      radicals. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway is a well
      established antioxidant pathway in various diseases such as diabetes, renal
      disease, various neurodegenerative disorders such as Parkinson's disease,
      Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis,
      traumatic brain injury, etc. Results: It has been observed that single-target
      therapies are inefficient in providing anticonvulsant and disease-modifying
      effects in epilepsy. CONCLUSIONS: So, preventing the progression of epilepsy by
      targeting Nrf2-activated antioxidant pathway along with the other established
      antiepileptic pathways can prove beneficial in epilepsy treatment.

PMID- 29447053
TI  - The Voice of the Clinical Practice Committee: More Than a Single Story.

PMID- 29447052
TI  - Commentary: Medicare Options.

PMID- 29447054
TI  - Medicare Assignment and Participation: Excerpts From Practical Tips for the
      Oncology Practice.

PMID- 29447055
TI  - Advanced Microengineered Lung Models for Translational Drug Discovery.
AB  - Lung diseases impose a significant socioeconomic burden and are a leading cause
      of morbidity and mortality worldwide. Moreover, respiratory medicine, unlike
      several other therapeutic areas, faces a disappointingly low number of new
      approved therapies. This is partly due to lack of reliable in vitro or in vivo
      models that can reproduce organ-level complexity and pathophysiological responses
      of human lung. Here, we examine new opportunities in application of recently
      emerged organ-on-chip technology to model human lung alveolus and small airway in
      preclinical drug development and biomarker discovery. We also discuss challenges
      that need to be addressed in coming years to further enhance the physiological
      and clinical relevance of these microsystems, enable their increased
      accessibility, and support their leap into personalized medicine.

PMID- 29447056
TI  - Investigating the psychometric properties of the revised child anxiety and
      depression scale (RCADS) in a non-clinical sample of Irish adolescents.
AB  - BACKGROUND: The psychometric properties of the Revised Child Anxiety and
      Depression Scale (RCADS) have been established cross-culturally, yet psychometric
      evidence is lacking for an English-speaking European population. AIM: This
      research sought to further cross-validate the measure in a non-clinical Irish
      adolescent sample, and to test for gender and age-based differential item
      functioning in depression and anxiety. METHOD: Participants were Irish second
      level school students (N = 345; 164 male; 12-18 years, M =14.97, SD = 1.44).
      Confirmatory factor analysis for categorical data (confirmatory item factor
      analysis) and multiple-indicator multiple-cause (MIMIC) modelling to identify
      items displaying possible metric invariance were conducted. RESULTS: A six-factor
      model fit the data well in both gender samples and both school cycles, as a proxy
      for age samples. Gender-based metric invariance for 5 of 47 items and age-based
      metric invariance for three items were identified. However, the magnitudes were
      small. Internal consistency and validity were also established. CONCLUSIONS:
      While, a number of items demonstrated minor metric invariance, there was no
      evidence that they influenced overall scores meaningfully. The RCADS can
      reasonably be used without adjustment in male and female, younger and older,
      adolescent samples. Findings have implications for the use of the RCADS in an
      English-speaking European population.

PMID- 29447057
TI  - Effect of resin infiltration and microabrasion on the microhardness, surface
      roughness and morphology of incipient carious lesions.
AB  - OBJECTIVE: The effects of resin infiltration and microabrasion on incipient
      carious lesions by surface microhardness, roughness and morphological
      assessments, and resistance to further acid attack of treated lesions were
      evaluated. MATERIAL AND METHODS: Eighty artificially-induced incipient lesions
      were randomly divided into five groups (n = 16): resin infiltration with an
      adhesive resin (Excite F, Ivoclar Vivadent, Schaan, Liechtenstein), resin
      infiltration with a resin infiltrant (Icon, DMG, Hamburg, Germany), microabrasion
      without polishing (Opalustre, Ultradent, South Jordan, UT, USA), microabrasion
      with polishing (Opalustre, Ultradent, Diamond Excel, FGM, Joinville, SC, Brazil),
      and distilled water (control group). All specimens were exposed to
      demineralization for another 10 d. Microhardness, roughness and morphological
      assessments were done at baseline, following initial demineralization, treatment
      and further demineralization. Data were analysed by the Kruskal-Wallis,
      Friedman's and Bonferroni tests (p < .05). RESULTS: Enamel lesions treated with
      resin infiltrant and microabrasion demonstrated similar hardness values, with a
      nonsignificant difference compared with sound enamel. Resin infiltration
      demonstrated lower roughness values than those of microabrasion, and the values
      did not reach the values of sound enamel. Further demineralization for 10 d did
      not affect the hardness but increased the roughness of infiltrated and
      microabraded enamel surfaces. Polishing did not influence the roughness of
      microabraded enamel surfaces. After resin infiltration, porosities on enamel were
      sealed completely. The surface structure was similar to that of the enamel
      conditioning pattern for microabraded enamel lesions. CONCLUSIONS: Within the
      limitations of this study, the icon infiltration and microabrasion technique
      appeared to be effective for improving microhardness. Icon appeared to provide
      reduced roughness, although not equal to sound enamel. Further research is needed
      to elucidate their clinical relevance.

PMID- 29447058
TI  - Training and post-disaster interventions for the psychological impacts on
      disaster-exposed employees: a systematic review.
AB  - BACKGROUND: When organisations are exposed to traumatic situations, such as
      disasters, often staff are not prepared for the potential psychological impact
      which can negatively affect their wellbeing. AIMS: To conduct a systematic review
      of the literature on psychological interventions aimed at improving staff
      wellbeing during or after disasters. METHOD: Four electronic literature databases
      were searched. Reference lists of relevant articles were hand-searched. RESULTS:
      Fifteen articles were included. Five studies suggested that pre-disaster skills
      training and disaster education can improve employee confidence. Ten studies on
      post-disaster interventions revealed mixed findings on the effectiveness of
      psychological debriefing and limited evidence for cognitive behavioural therapy,
      psychoeducation and meditation. CONCLUSIONS: Pre-disaster training and education
      can improve employees' confidence in their ability to cope with disasters. The
      routine use of post-disaster psychological debriefings is not supported; further
      research is needed to determine if debriefing interventions could be useful in
      some circumstances. Further research is needed to provide more evidence on the
      potential positive effects of cognitive behavioural therapy, psychoeducation and
      meditation. More experimental studies on psychological disaster interventions are
      needed.

PMID- 29447059
TI  - Therapeutic potential of Mucuna pruriens (Linn.) on ageing induced damage in
      dorsal nerve of the penis and its implication on erectile function: an
      experimental study using albino rats.
AB  - OBJECTIVE: To study the effect of ethanolic seed extract of Mucuna pruriens on
      damaged dorsal nerve of the penis (DNP) in aged rat in relation to penile
      erection. METHODS: The rats were divided into four groups Young (3 months), Aged
      (24 - 28 months), Aged + M. pruriens, and Young + M. pruriens (200 mg/kg b.w/60
      days) and were subjected to the hypophysial - gonadal axis, nerve conduction
      velocity (NCV), and penile reflex. DNP sections were stained with nitric oxide
      synthase (nNOS), nicotinamide adenine dinucleotide phosphate (NaDPH) diaphorase,
      androgen receptor (AR), and osmium tetroxide. Terminal deoxynucleotidyl
      transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining, electron
      microscopy(EM) and histometric analyses were done. RESULTS: Significant
      disturbance in hypophysial - gonadal axis was noted in aged rat. With reduced
      number of myelinated fibers, diameter, vacuolization, indentation of the myelin
      sheath, and degeneration. nNOS and its cofactor (NaDPH diaphorase) were reduced
      in aged rat DNP. NCV was slow in aged rats and concomitant poor penile reflex was
      also noted. AR showed reduced expression in aged rat DNP when compared to young
      and control groups. TUNEL positive cells were increased in aged rat DNP. These
      pathological changes were remarkably reduced or recovered in M. pruriens treated
      aged rats. CONCLUSIONS: The results indicate a multi-factorial therapeutic
      activity in penile innervations towards sustaining the penile erection in the
      presence of the extract in aged rats and justifying the claim of traditional
      usage.

PMID- 29447060
TI  - Treatment of selective mutism based on cognitive behavioural therapy,
      psychopharmacology and combination therapy - a systematic review.
AB  - BACKGROUND: Selective mutism (SM) is a debilitating childhood anxiety disorder
      characterized by a persistent lack of speech in certain social settings and is
      considered hard to treat. Cognitive behavioral therapy (CBT) and pharmacological
      treatments are the best described treatments in the literature. AIM: To test
      whether there is evidence on treatment based on CBT, medication or a combination
      of these. METHODS: Systematic and critical review of the literature on CBT and/or
      pharmacological treatments of SM. Literature was sought on PubMed, Embase and
      Psycinfo in March 2017. RESULTS: Of the included studies, six examined CBT, seven
      pharmacologic treatment and two a combination of these. Using CBT 53/60 children
      improved symptomatically whilst respectively 55/67 and 6/7 improved using
      pharmacologic- and combination-treatment. CONCLUSION: Pharmacologic treatment and
      especially CBT showed promising results supported by some degree of evidence,
      which combination treatment lacks. Yet small numbers, few RCTs, heterogeneous
      study designs, lack of consistent measures, short treatment and follow-up
      periods, generally limits the evidence. This needs focus in future research.

PMID- 29447062
TI  - Chronic Myelogenous Leukemia: Pregnancy in the Era of Stopping Tyrosine Kinase
      Inhibitor Therapy.

PMID- 29447061
TI  - Models to Predict Hepatitis B Virus Infection Among Patients With Cancer
      Undergoing Systemic Anticancer Therapy: A Prospective Cohort Study.
AB  - Purpose Most patients with cancer are not screened for hepatitis B virus (HBV)
      infection before undergoing anticancer therapy, and optimal screening strategies
      are unknown. We sought to develop selective HBV screening strategies for patients
      who require systemic anticancer therapy. Methods This prospective cohort study
      included adults age >= 18 years with solid or hematologic malignancies who
      received systemic anticancer therapy at a comprehensive cancer center during 2013
      and 2014. Patients underwent hepatitis B surface antigen, hepatitis B core
      antibody, and hepatitis B surface antibody testing, and completed a 19-question
      modified Centers for Disease Control and Prevention (CDC) HBV survey.
      Multivariable models that predict chronic or past HBV infection were developed
      and validated using bootstrapping. Results A total of 2,124 patients (mean age,
      58 +/- 13 years) completed the risk survey and HBV testing. Of these, 54% were
      women; 77% were non-Hispanic white, 11% Hispanic, 8% black, and 4% Asian; and 20%
      had a hematologic malignancy and 80% a solid tumor. Almost 12% were born outside
      the United States. The prevalence was 0.3% for chronic HBV infection and 6% for
      past HBV infection. Significant predictors of positive hepatitis B surface
      antigen or hepatitis B core antibody tests were as follows: men who had sex with
      men, black or Asian race, birthplace outside the United States, parent's
      birthplace outside the United States, household exposure to HBV, age >= 50 years,
      and history of injection drug use. The area under the receiver operating
      characteristic curve of the model on the basis of these seven predictors was 0.79
      (95% CI, 0.73 to 0.82). The modified CDC survey and brief tools with fewer than
      seven questions yielded similar false-negative rates (0% and 0% to 0.7%,
      respectively). Conclusion An internally validated risk tool performed as well as
      the modified CDC survey; however, more than 90% of patients who completed the
      tool would still require HBV testing. Universal HBV testing is more efficient
      than risk-based screening.

PMID- 29447063
TI  - Introduction to the special issue on technology and neuropsychological
      rehabilitation.

PMID- 29447064
TI  - Childhood Origins of Young Adult Environmental Behavior.
AB  - Prospective, longitudinal analyses revealed that over a 12-year period from ages
      6 to 18, individuals who grew up with mothers with more proenvironmental
      attitudes engaged in more proenvironmental behavior as young adults. A similar
      marginal association was uncovered between mothers' proenvironmental behaviors
      and the proenvironmental behavior of their young adult offspring. Maternal
      educational attainment, but not political ideology, was also associated with more
      proenvironmental behavior as children matured. Moreover, childhood time spent
      outdoors was positively associated with increased environmentally responsible
      behavior in young adulthood. Interestingly, one's own childhood proenvironmental
      behavior and attitude, at least as assessed at age 6, bear little on one's
      eventual proenvironmental behavior as a young adult. Finally, among this set of
      childhood factors, maternal education and childhood time spent outdoors were
      independent predictors of positive changes in environmental behavior from early
      childhood to young adulthood.

PMID- 29447065
TI  - Born criminal? Differences in structural, functional and behavioural
      lateralization between criminals and noncriminals.
AB  - Over 100 years ago Lombroso [(1876/2006). Criminal man. Durham: Duke University
      Press] proposed a biological basis for criminality. Based on inspection of
      criminals' skulls he theorized that an imbalance of the cerebral hemispheres was
      amongst 18 distinguishing features of the criminal brain. Specifically, criminals
      were less lateralized than noncriminals. As the advent of neuroscientific
      techniques makes more fine-grained inspection of differences in brain structure
      and function possible, we review criminals' and noncriminals' structural,
      functional, and behavioural lateralization to evaluate the merits of Lombroso's
      thesis and investigate the evidence for the biological underpinning of criminal
      behaviour. Although the body of research is presently small, it appears
      consistent with Lombroso's proposal: criminal psychopaths' brains show atypical
      structural asymmetries, with reduced right hemisphere grey and white matter
      volumes, and abnormal interhemispheric connectivity. Functional asymmetries are
      also atypical, with criminal psychopaths showing a less lateralized cortical
      response than noncriminals across verbal, visuo-spatial, and emotional tasks.
      Finally, the incidence of non-right-handedness is higher in criminal than non
      criminal populations, consistent with reduced cortical lateralization. Thus
      despite Lombroso's comparatively primitive and inferential research methods, his
      conclusion that criminals' lateralization differs from that of noncriminals is
      borne out by the neuroscientific research. How atypical cortical asymmetries
      predispose criminal behaviour remains to be determined.

PMID- 29447066
TI  - Inaugurating Rationalization: Three Field Studies Find Increased Rationalization
      When Anticipated Realities Become Current.
AB  - People will often rationalize the status quo, reconstruing it in an exaggeratedly
      positive light. They will even rationalize the status quo they anticipate,
      emphasizing the upsides and minimizing the downsides of sociopolitical realities
      they expect to take effect. Drawing on recent findings on the psychological
      triggers of rationalization, I present results from three field studies, one of
      which was preregistered, testing the hypothesis that an anticipated reality
      becoming current triggers an observable boost in people's rationalizations. San
      Franciscans rationalized a ban on plastic water bottles, Ontarians rationalized a
      targeted smoking ban, and Americans rationalized the presidency of Donald Trump,
      more in the days immediately after these realities became current compared with
      the days immediately before. Additional findings show evidence for a mechanism
      underlying these behaviors and rule out alternative accounts. These findings
      carry implications for scholarship on rationalization, for understanding protest
      behavior, and for policymakers.

PMID- 29447068
TI  - Microbial Culturomics Broadens Human Vaginal Flora Diversity: Genome Sequence and
      Description of Prevotella lascolaii sp. nov. Isolated from a Patient with
      Bacterial Vaginosis.
AB  - Microbial culturomics is a new subfield of postgenomic medicine and omics
      biotechnology application that has broadened our awareness on bacterial diversity
      of the human microbiome, including the human vaginal flora bacterial diversity.
      Using culturomics, a new obligate anaerobic Gram-stain-negative rod-shaped
      bacterium designated strain khD1T was isolated in the vagina of a patient with
      bacterial vaginosis and characterized using taxonogenomics. The most abundant
      cellular fatty acids were C15:0 anteiso (36%), C16:0 (19%), and C15:0 iso (10%).
      Based on an analysis of the full-length 16S rRNA gene sequences, phylogenetic
      analysis showed that the strain khD1T exhibited 90% sequence similarity with
      Prevotella loescheii, the phylogenetically closest validated Prevotella species.
      With 3,763,057 bp length, the genome of strain khD1T contained (mol%) 48.7 G + C
      and 3248 predicted genes, including 3194 protein-coding and 54 RNA genes. Given
      the phenotypical and biochemical characteristic results as well as genome
      sequencing, strain khD1T is considered to represent a novel species within the
      genus Prevotella, for which the name Prevotella lascolaii sp. nov. is proposed.
      The type strain is khD1T ( = CSUR P0109, = DSM 101754). These results show that
      microbial culturomics greatly improves the characterization of the human
      microbiome repertoire by isolating potential putative new species. Further
      studies will certainly clarify the microbial mechanisms of pathogenesis of these
      new microbes and their role in health and disease. Microbial culturomics is an
      important new addition to the diagnostic medicine toolbox and warrants attention
      in future medical, global health, and integrative biology postgraduate teaching
      curricula.

PMID- 29447069
TI  - After Aylan Kurdi: How Tweeting About Death, Threat, and Harm Predict Increased
      Expressions of Solidarity With Refugees Over Time.
AB  - Viral social media content has been heralded for its power to transform policy,
      but online responses are often derided as "slacktivism." This raises the
      questions of what drives viral communications and what is their effect on support
      for social change. We addressed these issues in relation to Twitter discussions
      about Aylan Kurdi, a child refugee who died en route to the European Union. We
      developed a longitudinal paradigm to analyze 41,253 tweets posted 1 week before
      the images of Aylan Kurdi emerged, the week they emerged, and 10 weeks afterward
      at the time of the Paris terror attacks. Tweeting about death before the images
      emerged predicted tweeting about Aylan Kurdi, and this, sustained by discussion
      of harm and threat, predicted the expression of solidarity with refugees 10 weeks
      later. Results suggest that processes of normative conflict and communication can
      be intertwined in promoting support for social change.

PMID- 29447067
TI  - Regulation of eukaryotic elongation factor 1 alpha (eEF1A) by dynamic lysine
      methylation.
AB  - Lysine methylation is a frequent post-translational protein modification, which
      has been intensively studied in the case of histone proteins. Lysine methylations
      are also found on many non-histone proteins, and one prominent example is
      eukaryotic elongation factor 1 alpha (eEF1A). Besides its essential role in the
      protein synthesis machinery, a number of non-canonical functions have also been
      described for eEF1A, such as regulation of the actin cytoskeleton and the
      promotion of viral replication. The functional significance of the extensive
      lysine methylations on eEF1A, as well as the identity of the responsible lysine
      methyltransferases (KMTs), have until recently remained largely elusive. However,
      recent discoveries and characterizations of human eEF1A-specific KMTs indicate
      that lysine methylation of eEF1A can be dynamic and inducible, and modulates mRNA
      translation in a codon-specific fashion. Here, we give a general overview of
      eEF1A lysine methylation and discuss its possible functional and regulatory
      significance, with particular emphasis on newly discovered human KMTs.

PMID- 29447070
TI  - Reading Your Mind While You Are Reading-Evidence for Spontaneous Visuospatial
      Perspective Taking During a Semantic Categorization Task.
AB  - Recent studies have demonstrated people's propensity to adopt others'
      visuospatial perspectives (VSPs) in a shared physical context. The present study
      investigated whether spontaneous VSP taking occurs in mental space where another
      person's perspective matters for mental activities rather than physical actions.
      Participants sat at a 90 degrees  angle to a confederate and performed a semantic
      categorization task on written words. From the participants' point of view, words
      were always displayed vertically, while for the confederate, these words appeared
      either the right way up or upside down, depending on the confederate's sitting
      position. Participants took longer to categorize words that were upside down for
      the confederate, suggesting that they adopted the confederate's VSP without being
      prompted to do so. Importantly, the effect disappeared if the other's visual
      access was impeded by opaque goggles. This demonstrates that human adults show a
      spontaneous sensitivity to others' VSP in the context of mental activities, such
      as joint reading.

PMID- 29447071
TI  - A social media intervention to improve hypoglycemia management at a multicenter
      hospital: a quality improvement pilot for clinical nurses.
AB  - BACKGROUND: Hypoglycemia poses significant risk to inpatients. Nursing management
      of hypoglycemia is a challenge, despite established best practice guidelines.
      Social media is an effective tool for sharing information and could overcome
      barriers to clinical education at a multicenter hospital. AIMS: The purpose of
      this quality improvement intervention was to create and disseminate social media
      posts about best practices in hypoglycemia management. DESIGN: An unmatched pre
      and post-survey assessed nursing knowledge of hypoglycemia management. METHODS:
      Social media posts were created to visually outline the steps for hypoglycemia
      management over 2 weeks, across a nursing social media platform. We assessed the
      reach of the posts via Facebook and a survey. RESULTS: The posts reached 2962
      users during the first week, and 1491 users the second week. CONCLUSIONS: A
      social media intervention can have a substantial reach and distribute information
      across a multicenter hospital. Additional study is needed to determine what
      factors could support an increase in nursing knowledge through a social media
      campaign.

PMID- 29447072
TI  - Construction and structure studies of DNA-bipyridine complexes as versatile
      scaffolds for site-specific incorporation of metal ions into DNA.
AB  - The facile construction of metal-DNA complexes using 'Click' reactions is
      reported here. A series of 2'-propargyl-modified DNA oligonucleotides were
      initially synthesized as structure scaffolds and were then modified through
      'Click' reaction to incorporate a bipyridine ligand equipped with an azido group.
      These metal chelating ligands can be placed in the DNA context in site-specific
      fashion to provide versatile templates for binding various metal ions, which are
      exchangeable using a simple EDTA washing-and-filtration step. The constructed
      metal-DNA complexes were found to be thermally stable. Their structures were
      explored by solving a crystal structure of a propargyl-modified DNA duplex and
      installing the bipyridine ligands by molecular modeling and simulation. These
      metal-DNA complexes could have wide applications as novel organometallic
      catalysts, artificial ribonucleases, and potential metal delivery systems.

PMID- 29447073
TI  - The benefits and risks of expressing the POT and FOT family of oligopeptide
      transporters in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, all strains possess a gene for the
      evolutionarily conserved POT family peptide transporter, Ptr2; however, the genes
      for a novel FOT family transporter were found only in some wine brewing strains.
      The substrate specificity of the POT and FOT family of transporters was compared.
      Among the naturally occurring oligopeptides that were tested, Lys-Leu and Arg-Phe
      were Ptr2-specific substrates. Artificial dipeptide aspartame was imported
      specifically through the FOT transporter, but the structurally similar Asp-Phe
      was a substrate of both FOT and Ptr2 transporters. Furthermore, only the FOT
      transporter was important for high sensitivity to an antibiotic puromycin. These
      results demonstrate that the POT and FOT family of transporters have distinct
      substrate preferences although both transporters import overlapping dipeptide
      substrates. Having POT and FOT transporters is advantageous for cells to acquire
      nutrients, but also detrimental when these cells are exposed to the toxic
      molecules of their substrates.

PMID- 29447074
TI  - Social cognition in the course of psychosis and its correlation with biomarkers
      in a male cohort.
AB  - INTRODUCTION: Patients diagnosed with schizophrenia display deficits in Theory of
      Mind (ToM) and Emotion Perception (EP) even before the appearance of full-blown
      symptomatology. METHODS: We evaluated ToM and EP in a male cohort consisting of
      25 First Episode Psychosis (FEP) and 16 relapsed schizophrenic patients (CHRON)
      compared to 12 subjects in Ultra-high Risk (UHR) and 23 healthy controls (CTR).
      Furthermore, we measured the levels of Cortisol, Insulin like Growth Factor (IGF
      1), TNF-a, TNF-b and several interleukins as potential biomarkers. RESULTS:
      Deficits in EP and ToM were found in FEP, CHRON patients and UHR subjects
      compared to CTR. The impairments in these two domains seem to follow different
      patterns in the course of psychosis. EP was more impaired in subjects with a
      longer history of symptomatology whereas there was no statistically significant
      difference regarding ToM. On the other hand IL-4 was the only biomarker
      correlated to ToM and EP scores in two different samples of our study.
      CONCLUSION: Social Cognition (SC) domains are impaired in patients with psychosis
      as well as in UHR subjects compared to healthy controls. There are differences in
      the progress of ToM and EP deficits in the course of psychosis. Interleukins as
      IL-4 could correlate to SC.

PMID- 29447075
TI  - Propionibacterium acnes Has Low Susceptibility to Chlorhexidine Digluconate.
AB  - BACKGROUND: The skin bacterium Propionibacterium acnes has been reported to be
      responsible for surgical site infections (SSIs). Skin disinfection before surgery
      therefore is of the utmost importance in the prevention of SSIs caused by skin
      bacteria. METHODS: We assessed the susceptibility of clinical isolates of two
      skin bacteria, P. acnes and Staphylococcus epidermidis, to disinfectants.
      RESULTS: The range of chlorhexidine digluconate (CHG) minimum inhibitory
      concentrations (MICs) for P. acnes isolates was 0.25-1 mcg/mL. Furthermore, the
      minimum bactericidal concentrations (MBCs) for a range of disinfectants were
      determined to evaluate their rapid bactericidal activity. The MBC range of CHG
      against the P. acnes isolates was 4,096->32,768 mcg/mL (MBC80 16,384 mcg/mL)
      after one minute of exposure and 1,024-32,768 mcg/mL (MBC80 8,192 mcg/mL) after
      five minutes, indicating that some strains required a CHG MBC higher than the
      commercial concentration of 2% (20,000 mcg/mL). In contrast, the MBCs of
      glutaraldehyde, sodium hypochlorite, povidone-iodine, ethanol, benzalkonium
      chloride, and olanexidine gluconate were all sufficiently lower than their
      commercial concentrations. In S. epidermidis, the MBC range of CHG was 128-1,024
      mcg/mL at one minute of exposure and 4-8 mcg/mL at five minutes. CONCLUSIONS:
      Different skin bacteria have different susceptibilities to disinfectants. To
      prevent SSIs, the selected disinfectant agent and the disinfection time should
      have bactericidal activity toward all the bacteria that pose a risk of infection.

PMID- 29447076
TI  - A double-blind, placebo-controlled, randomised clinical study of the effect of
      pork collagen peptide supplementation on atherosclerosis in healthy older
      individuals.
AB  - We examined whether baPWV could be affected by pork collagen peptide (CP)
      ingestion. Seventy subjects were randomized into two groups (2.5 g/day CP and 2.5
      g/day placebo). A significant reduction in baPWV was observed in the CP group
      compared to the placebo group. This study demonstrated that pork CP may
      contribute to the prevention of atherosclerosis in elderly.

PMID- 29447078
TI  - Effects of Peutz-Jeghers syndrome (PJS) causing missense mutations L67P, L182P,
      G242V and R297S on the structural dynamics of LKB1 (Liver kinase B1) protein.
AB  - The liver kinase B1 (LKB1) is encoded by LKB1 gene. Several pathogenic mutations
      of LKB1 causing Peutz-Jeghers syndrome and also cancers in breast, gastric,
      pancreas, and colon have been reported. The present study is focused to analyze
      the effects on the structural dynamics of LKB1 caused by the 4 pathogenic
      missense mutations (L67P, L182P, G242V, and R297S), which are reported to reduce
      the catalytic activity. In this study, the structural changes of LKB1 in apo- and
      in heterotrimeric complex (LKB1-STRADalpha-MO25alpha) form with wild and mutated
      LKB1 are investigated using all atomistic molecular dynamic simulation. The
      present study reveals that these four mutations initiate local structural
      distortions and the solvent accessibility of the surrounding regions of ATP
      binding pocket such as glycine-rich loop, alphaB and alphaC loop, activation and
      catalytic loops. The mutations of L67P, L182P, and G242 V induce distortions of
      the secondary structure of beta1-beta3 sheets, pi - pi interaction (observed
      between Phe204 of LKB1 and Phe243 of MO25alpha), and increase the helical
      properties (both helical twist and length) of the adjacent alphaH-helix,
      respectively. The active kinase features like the conformation of catalytic and
      activation loops, salt bridge and, finally, the formation of stable R- and C
      hydrophobic spines are also found to be perturbed by these mutations. Hence, the
      observed mutation-induced structural distortions fail to coordinate the essential
      binding nature of LKB1 with STRADalpha and MO25alpha, which eventually affects
      the native function of LKB1. These observations are in line with the
      experimentally reported reduced kinase activity of LKB1.

PMID- 29447077
TI  - Identification of proteins that bind to the neuroprotective agent neoechinulin A.
AB  - Neoechinulin A is an indole alkaloid with several biological activities. We
      previously reported that this compound protects neuronal PC12 cells from
      cytotoxicity induced by the peroxynitrite generator 3-morpholinosydnonimine (SIN
      1), but the target proteins and precise mechanism of action of neoechinulin A
      were unclear. Here, we employed a phage display screen to identify proteins that
      bind directly with neoechinulin A. Our findings identified two proteins,
      chromogranin B and glutaredoxin 3, as candidate target binding partners for the
      alkaloid. QCM analyses revealed that neoechinulin A displays high affinity for
      both chromogranin B and glutaredoxin 3. RNA interference-mediated depletion of
      chromogranin B decreased the sensitivity of PC12 cells against SIN-1. Our results
      suggested chromogranin B is a plausible target of neoechinulin A.

PMID- 29447079
TI  - Flucloxacillin-induced hypokalaemia: a case report.
AB  - OBJECTIVE AND IMPORTANCE: Flucloxacillin is a narrow-spectrum beta-lactam
      antibiotic with activity against penicillinase producing staphylococci and
      streptococci. Severe hypokalaemia is an uncommon, but serious adverse effect in
      patients treated with penicillin derivates. CLINICAL PRESENTATION: We report a
      case of severe hypokalaemia in a patient treated with high dose intravenous
      flucloxacillin. CONCLUSION: This case report highlights the importance of
      monitoring electrolytes during treatment with high dose flucloxacillin. If severe
      hypokalaemia is noted during treatment, this should be considered in the
      differential diagnosis.

PMID- 29447080
TI  - Improved lower extremity pedaling mechanics in individuals with stroke under
      maximal workloads.
AB  - Background Individuals with stroke present with motor control deficits resulting
      in the abnormal activation and timing of agonist and antagonist muscles and
      inefficient movement patterns. The analysis of pedaling biomechanics provides a
      window into understanding motor control deficits, which vary as a function of
      workload. Understanding the relationship between workload and motor control is
      critical when considering exercise prescription during stroke rehabilitation.
      Objectives To characterize pedaling kinematics and motor control processes under
      conditions in which workload was systematically increased to an eventual patient
      specific maximum. Methods A cohort study was conducted in which 18 individuals
      with chronic stroke underwent a maximal exertion cardiopulmonary exercise test on
      a stationary cycle ergometer, during which pedaling torque was continuously
      recorded. Measures of force production, pedaling symmetry, and pedaling
      smoothness were obtained. Results Mean Torque increased significantly (p < 0.05)
      for both legs from initial to terminal workloads. Mean torque Symmetry Index,
      calculated for down and upstroke portions of the pedaling action, improved from
      0.37(0.29) to 0.29(0.35) during downstroke (p = 0.007), and worsened during the
      upstroke: -0.37(0.38) to -0.62(0.46) (p < 0.001) from initial to terminal
      workloads. Low Torque Duration improved from initial to terminal workloads,
      decreasing from 121.1(52.9) to 58.1(39.6) degrees (p < 0.001), respectively.
      Smoothness of pedaling improved significantly from initial to terminal workloads
      (p < 0.001). Conclusions Improved pedaling kinematics at terminal workloads
      indicate that individuals with stroke demonstrate improved motor control with
      respect to the timing, sequencing, and activation of hemiparetic lower extremity
      musculature compared to lower workloads. Therapeutic prescription involving
      higher resistance may be necessary to sufficiently engage and activate the
      paretic lower extremity.

PMID- 29447081
TI  - Is neuropathic pain associated with cardiac sympathovagal activity changes in
      patients with breast cancer?
AB  - Objective Heart rate variability (HRV) is a good indicator of the autonomic
      nervous system (ANS) activity. A few studies have been conducted recently and
      have shown a relationship between reduced HRV and conditions that lead to
      neuropathic pain (NP). In this study, we aimed to investigate whether NP is
      associated with changes in cardiac sympathovagal activity in patients with breast
      cancer (BC). Methods We used the Leeds Assessment of Neuropathic Symptoms and
      Signs (LANSS) questionnaire to evaluate NP in 70 patients with BC. The patients
      were subjected to a 24-h Holter ECG monitorization to determine heart rate
      variability (HRV). Standard deviation (SD) of the normal-to-normal RR intervals
      (SDNN), SD of the mean of the RR intervals (SDAAN), mean of the SD of the NN
      interval (SDNN Index), low-frequency component/high-frequency component ratio
      (LF/HF), and the mean heart rate of the patients were recorded. Results According
      to the LANSS questionnaire, 18 (25.7%) of the patients were classified as NP (+).
      The SDNN (P = 0.001), SDAAN (P = 0.003), and SDDN index (P = 0.007) were
      significantly lower in patients with NP than in patients without NP, whereas
      LF/HF ratio (P = 0.000) and mean heart rate were found to be significantly higher
      in patients with NP (P = 0.006). Conclusion According to our findings, NP (+)
      patients with BC had increased cardiac sympathetic activity, which was suggested
      to be associated with increased cardiovascular morbidity and mortality.

PMID- 29447082
TI  - Radiologic Measurement of Brain Swelling in Patients with Large Hemispheric
      Infarctions During Targeted Temperature Management.
AB  - Brain herniation is most often the result of severe brain swelling and can
      rapidly lead to death or brain death. We retrospectively identified radiologic
      indicators to evaluate the effects of targeted temperature management (TTM) on
      the extent of cerebral edema and determine the cutoff values that best predict
      TTM outcomes in patients with large hemispheric infarction. We retrospectively
      reviewed brain computed tomography (CT) scans of 21 patients with large
      hemispheric infarctions, who were treated with TTM. We excluded 4 patients whose
      CT scans were inadequate for evaluation, which left 17 patients. We divided the
      patients into success and failure groups. TTM failure was defined as death or the
      need for decompressive hemicraniectomy (DHC) after TTM. Infarction size was
      measured as the total restricted area in diffusion-weighted imaging that was
      performed on admission. CT scans were obtained on the first and second days after
      TTM initiation and then every 2 days. We measured septum pellucidum shifts (SPS)
      and pineal gland shifts (PGS) on CT scans. The median time from symptom onset to
      TTM initiation was 14.5 hours. Ten patients were successfully treated with TTM,
      six patients died, and one patient underwent a DHC. Initial infarction sizes were
      not significantly different between the success and failure groups (p = 0.529),
      but the SPS and PGS at 36-72 hours after TTM initiation were (mean SPS: 5.0 vs.
      14.9 mm, p = 0.001; mean PGS: 2.3 vs. 7.9 mm, p = 0.001). The sensitivity and
      negative predictive value for TTM failure caused by cerebral edema (SPS >=9.25 mm
      and PGS >=3.70 mm) at 36-72 hours after TTM initiation were both 100%. The SPS
      and PGS on CT scans taken 36-72 hours after TTM initiation may help to estimate
      the effect of TTM on cerebral edema and guide further treatment.

PMID- 29447084
TI  - Binding site identification of anticancer drug gefitinib to HSA and DNA in the
      presence of five different probes.
AB  - This study was carried out to evaluate the binding interaction of gefitinib (GEF)
      with human serum albumin (HSA) and calf thymus DNA (ct-DNA) using fluorescence,
      UV-Visible, zeta potential measurements and molecular docking methods in order to
      understand its pharmacokinetic mechanism. By increasing the temperature, a steady
      decrease in Stern-Volmer quenching constants was observed for HSA binding
      properties; this indicates a static type of fluorescence quenching. Negative
      values were calculated for Gibbs free energy (DeltaG), enthalpy (DeltaH), and
      entropy (DeltaS) changes, indicating that the reaction is spontaneous and
      enthalpy-driven. Probe competitive experimental results showed that GEF contains
      the same binding site as warfarin and are consistent with modeling results. The
      zeta potential of the HSA increased with increasing GEF, which represents the
      presence of electrostatic interactions in the system. DNA binding properties were
      investigated in the presence of three probes. The experimental results showed
      that by increasing GEF to DNA-AO (acridine-orange) and DNA-MB (methylene-blue)
      system, the fluorescence intensity and absorbance spectra had no considerable
      change. Furthermore, with the addition of GEF to DNA, the zeta potential
      decreased gradually, indicating that the hydrophobic interaction between the GEF
      and the bases of DNA is the major factor. Thus, GEF can bind to DNA via a groove
      binding mode. It was also found that GEF entered into the minor groove in the A-T
      rich region of DNA fragment and bind via van der-Waals forces and three H-bond
      with double strands of DNA. This is in good agreement with experimental results.

PMID- 29447083
TI  - In complete SCI patients, long-term functional electrical stimulation of
      permanent denervated muscles increases epidermis thickness.
AB  - Our studies have shown that atrophic Quadriceps muscles from spinal cord injury
      patients suffering with permanent denervation-induced atrophy and degeneration of
      muscle fibers, were almost completely rescued to normal size after two years of
      home-based functional electrical stimulation (h-bFES). Because we used surface
      electrodes to stimulate the muscle, we wanted to know how the skin was affected
      by the treatments. Here, we report preliminary data from histological morphometry
      of Hematoxylin-Eosin-stained paraffin-embedded skin sections harvested from the
      legs of three SCI patients before and after two years of h-bFES. Despite the
      heterogeneity of gender and time from SCI, comparing pre vs post h-bFES in these
      three SCI patients, the data show that: (1) In one subject skin biopsies from
      both the right and left leg experienced a statistically significant increase in
      thickness of the epidermis after two years of H-bFES; (2) In the other two
      subjects, one leg showed a significant increase in epidermis thickness, while in
      the other leg there was either small positive or negative non-significant changes
      in epidermis thickness; and (3) more importantly, comparison of grouped data from
      the three subjects shows that there was a significant 28% increase in the
      thickness of the epidermis in response to two years of h-bFES rehabilitation. In
      conclusion, the three educational cases show a long-term positive modulation of
      epidermis thickness after two years of h-bFES, thus extending to skin the
      positive results previously demonstrated in skeletal muscle, specifically, a
      substantial recovery of muscle mass and contractile function after long-term h
      bFES.

PMID- 29447085
TI  - Paritaprevir/ritonavir/ombitasvir plus dasabuvir in HIV/HCV-coinfected patients
      with genotype 1 in real-life practice.
AB  - Background Data on the efficacy, safety, and concomitant use with other drugs of
      the combination ritonavir-boosted paritaprevir/ombitasvir plus dasabuvir (PrOD)
      in HIV/HCV-coinfected patients in real life are limited. The objectives of this
      study were to analyze these topics in HIV/HCV-coinfected subjects bearing HCV
      genotype 1 (GT1). Methods One hundred and eighty-two HIV/HCV-coinfected patients
      with GT1 (87 1a, 71 1b, 23 other) treated with PrOD, plus ribavirin (RBV) in 119
      cases, in routine clinical practice were analyzed. The main variable of efficacy
      was sustained virological response (SVR) 12 weeks after completing therapy in an
      intention-to-treat (ITT) analysis and that of safety treatment discontinuation
      because of adverse effects. Factors associated with SVR were analyzed with a
      modified ITT (mITT) strategy. Results One hundred and seventy-two (94%) patients
      attained SVR, 3 (2%) experienced a relapse and two (1%) discontinued therapy due
      to adverse events. The rates of SVR in subjects with GT 1a and 1b by mITT were,
      respectively, 97% and 98%. Sixty-five (98%) out of 66 patients with cirrhosis and
      107 (98%) out of 110 (p = 1) non-cirrhotics achieved SVR. Fifty-five (95%)
      patients on concomitant darunavir therapy developed SVR vs. 117 (99%) (p = 0.105)
      of those without DRV. RBV dose was reduced in 13 (11%) patients and permanently
      discontinued in 2 (2%), with no impact on SVR. Conclusions PrOD is highly
      effective and well tolerated in HIV/HCV-coinfected patients with GT1 in routine
      clinical practice. RBV is often required. However, RBV dose reduction or
      discontinuation is uncommonly needed and do not impair the SVR rate.

PMID- 29447086
TI  - Vitamin D down-regulates the expression of some Th17 cell-related cytokines, key
      inflammatory chemokines, and chemokine receptors in experimental autoimmune
      encephalomyelitis.
AB  - OBJECTIVES: A spectrum of immunomodulatory properties was attributed to vitamin D
      (VD). Here, the VD effects on expression of some Th17 cell- related cytokines,
      chemokines and chemokine receptors were investigated in experimental autoimmune
      encephalomyelitis (EAE). METHODS: One group of C57BL/6 mice, considered as
      healthy group, was treated with phosphate buffered saline (PBS). EAE was induced
      in other three groups and treated from day +3 to +30 with PBS, olive oil (VD
      vehicle) or 200 ng of VD. At day 31, the expression of interleukin-17 (IL-17), IL
      23, chemokine (C-C motif) ligand 20 (CCL20), CCL22, CC chemokine receptor 4
      (CCR4) and CCR6 in spinal cord and serum IL-17 and IL-23 levels were measured by
      real-time PCR and ELISA, respectively. RESULTS: The expression of IL-17, IL-23
      P19, IL-23 P40, CCL20, CCL22 and CCR4 in spinal cord and serum IL-17 and IL-23
      levels in PBS-administrated EAE mice were significantly increased compared with
      healthy group. In EAE mice treated with VD, the expression of aforementioned
      parameters was significantly reduced in comparison with PBS-administrated EAE
      mice. CONCLUSION: VD down-regulates the expression of some inflammatory
      cytokines, chemokines and chemokine receptors in EAE mice. The possible
      therapeutic potential of VD in multiple sclerosis can be considered in future
      investigation.

PMID- 29447087
TI  - A preliminary survey of Chlamydia psittaci genotypes from native and introduced
      birds in New Zealand.
AB  - AIM: To describe the Chlamydia psittaci genotypes in samples from native and
      introduced birds from New Zealand by analysis of the sequence variation of the
      ompA gene. METHODS: DNA was extracted from samples collected from a non-random
      sample of birds; either swabs from live asymptomatic birds or birds with clinical
      signs, or formalin-fixed, paraffin-embedded (FFPE) samples from historical post
      mortem cases. The presence of C. psittaci in all samples had been confirmed using
      a quantitative PCR assay. The C. psittaci ompA gene was amplified and sequenced
      from samples from 26 native and introduced infected birds comprising 12 different
      species. These sequences were compared to published available C. psittaci
      genotypes. RESULTS: Genotypes A and C of C. psittaci were identified in the
      samples. Genotype A was identified in samples from nine birds, including various
      native and introduced species. Genotype C was identified in samples from 16
      different waterfowl species, and a mixed infection of both genotypes was found in
      a kaka (Nestor meridionalis). In native birds, C. psittaci infection was
      confirmed in seven new host species. CONCLUSIONS AND CLINICAL RELEVANCE: Two
      genotypes (A and C) of C. psittaci were found in samples from a wider range of
      both native and introduced species of birds in New Zealand than previously
      reported. Both genotypes have been globally associated with significant disease
      in birds and humans. These initial results suggest the host range of C. psittaci
      in New Zealand birds is under-reported. However, the prevalence of C. psittaci
      infection in New Zealand, and the associated impact on avian and public health,
      remains to be determined. There are biosecurity implications associated with the
      importation of birds to New Zealand if there is a limited diversity of C.
      psittaci genotypes present.

PMID- 29447088
TI  - Increasing incidence and survival of head and neck cancers in Denmark: a nation
      wide study from 1980 to 2014.
AB  - BACKGROUND: The purpose of the study was to determine trends in age-adjusted
      incidence rates (AAIR) and survival probability in head and neck cancers (HNCs)
      in the Danish population from 1980 to 2014. MATERIAL AND METHODS: All patients
      registered with HNC in the nationwide Danish Cancer Registry from 1980 to 2014
      were included. We evaluated the AAIR per 100,000 and the average annual percent
      change (AAPC). The relative survival probability at 5 years was calculated in
      relation to gender, anatomical location and histology, and we constructed age
      period-cohort models of incidence. RESULTS: About 34,606 patients were included
      (64.7% men). The AAIR increased from 9.1 per 100,000 in 1980 to 17.4 per 100,000
      in 2014 with an AAPC of 2.1%. The greatest incidence increase was observed in
      oropharyngeal cancer (AAPC: 5.4%) followed by hypopharyngeal cancer (AAPC: 4.2%).
      Adenocarcinomas had the highest AAPC (5.0%) followed by squamous cell carcinomas
      (AAPC: 2.0%). The AAPC was significantly higher in women (2.4%) compared with men
      (1.6%). For all HNC patients, the relative survival at 5 years rose significantly
      from 49.0% in 1980-1984 to 62.4% in 2010-2014. Women had a significantly higher
      survival than men with a relative survival of 61.7% compared to 50.0% in men.
      Laryngeal cancer had the best survival probability of cancers in the upper
      aerodigestive tract with hypopharyngeal cancer having the poorest survival.
      CONCLUSION: This nation-wide study showed a significant rise in incidence of HNC
      for men and women along with a significant increase in relative survival.
      Oropharyngeal cancer had the highest increase in incidence followed by
      hypopharyngeal cancer which showed the poorest survival of HNCs.

PMID- 29447089
TI  - Aflibercept Versus Bevacizumab and/or Ranibizumab for Recurrent Macular Edema
      Secondary to Central Retinal Vein Occlusion.
AB  - PURPOSE: To compare functional and anatomic outcomes of treatment with
      intravitreal aflibercept versus bevacizumab and/or ranibizumab in patients with
      recurrent macular edema (ME) secondary to central retinal vein occlusion (CRVO).
      METHODS: Retrospective, comparative case series of patients with recurrent ME in
      the setting of CRVO. Patients with recurrent ME received treatment with
      aflibercept (Group 1, G1) or bevacizumab and/or ranibizumab (Group 2, G2).
      Primary outcome measures were best-corrected visual acuity (BCVA) and central
      foveal thickness (CFT). RESULTS: Of the 20 eyes (20 patients) with recurrent ME
      included in the study, 9 received aflibercept (G1) and 11 received bevacizumab
      and/or ranibizumab (G2). Median BCVA at recurrence of ME and at most recent
      follow-up was 20/60 (G1) and 20/80 (G2) and 20/40 (G1) and 20/50 (G2, P > 0.05
      for all comparisons), respectively. Median CFT at recurrence of ME and at most
      recent follow-up was 492 MUm (G1) and 448 MUm (G2) and 291 MUm (G1) and 295 MUm
      (G2, P > 0.05 for all comparisons), respectively. Complete resolution of ME for
      at least 4 months was found in 78% (G1) and 55% (G2) of patients with a median
      injection free interval of 11 (G1) and 13 (G2) months (P > 0.05). CONCLUSIONS: In
      patients with recurrent ME secondary to CRVO, there was improvement in BCVA and
      CFT in all groups, although patients treated with aflibercept showed a trend
      toward better anatomical outcomes decreased need for recurrent injections.

PMID- 29447091
TI  - Obesity in pregnancy: a comparison of four national guidelines.
AB  - BACKGROUND: Obesity in pregnancy has become one of the most important challenges
      in obstetrical care given its prevalence and potential adverse impact on both
      mother and fetus. The primary objective of this descriptive review is to identify
      common themes and distinctions within the current recommendations for maternal
      obesity in the most updated version of four published national guidelines.
      METHODS: We reviewed the following guidelines for obesity in pregnancy: American
      College of Obstetricians and Gynecologists (ACOG) 2015, Royal Australian and New
      Zealand College of Obstetricians and Gynecologists (RANZCOG) 2013, Royal College
      of Obstetrics and Gynecology (RCOG) 2010, and Society of Obstetrics and
      Gynecologists of Canada (SOGC) 2010. RESULTS: There were no major contradictions
      between the guidelines, however, variations did exist. Recognition of overweight
      and obese populations prenatally was uniformly emphasized, so that appropriate
      nutrition and exercise counseling could be provided prior to pregnancy. Obesity
      in pregnancy was consistently defined as a body mass index of 30 kg/m2 or more,
      and weight gain recommendations were in line with the Institute of Medicine
      guidelines. Counseling patients regarding the specific maternal and fetal
      complications in pregnancy, delivery, and postpartum which are associated with
      obesity was consistently emphasized. Most guidelines recommended early screening
      for gestational diabetes, however, specific details were not provided. All
      guidelines stressed the importance of available resources in clinics and the
      operating room specific to the obese population. Disparities were found regarding
      recommendations for high-dose folic acid, vitamin D supplementation, and low-dose
      aspirin. Thromboprophylaxis is a matter of debate, with most guidelines
      recommending use on an individual patient basis. CONCLUSIONS: In general, the
      guidelines emphasized the importance of counseling women regarding the risks
      associated with obesity in pregnancy, and stressed the necessity of screening for
      these adverse outcomes. Initiatives to develop common terminology and reporting
      of outcomes in women's health are important for the development of cohesive and
      uniform recommendations for patient care. Disparities existed with respect to
      management strategies and where the further research and systematic reviews
      should be targeted, to allow clinicians to provide an appropriate obstetrical
      care pathway for obese women.

PMID- 29447092
TI  - Evolution of muscular fatigue in periscapular and rotator cuff muscles during
      isokinetic shoulder rotations.
AB  - To this day, how shoulder muscles react to a strong fatigue stimulus during
      dynamic shoulder rotations remains unknown. The aims of this study were to assess
      the effect of repeated maximal internal-external isokinetic shoulder rotations on
      shoulder strength and muscle activity. Twenty-four individuals completed a 50
      repetition fatiguing isokinetic protocol while electromyography was recorded on
      eleven muscles of the shoulder girdle. Time-frequency transformation and an ANOVA
      model using statistical parametric mapping methods were used to analyze shifts in
      instantaneous median frequency (MDF) between each 10-repetition Blocks. Peak
      torques decreased in both internal and external rotation (P < 0.01) by 24.8% on
      average which indicated the presence of fatigue. Significant decrease in MDF (P <
      0.01) was observed for pectoralis, middle deltoid, upper, middle and lower
      trapezius, infraspinatus and subscapularis muscles. The observed fatigue to the
      periscapular and rotator cuff muscles suggests that shoulder stability could be
      compromised during repeated shoulder rotations, which could underlie the
      increased risk of scapular dyskinesis and shoulder impingement during fatiguing
      tasks. The present study provides a deeper understanding on the manifestations of
      fatigue within muscles of the shoulder girdle and the results could be applied
      toward improvements in athlete shoulder injury prevention and rehabilitation
      programs.

PMID- 29447093
TI  - Drug-Addicted Oncology Practice: The Drug Test.
AB  - PURPOSE: The buy-and-bill model of pharmaceuticals has been an economic reality
      for medical oncology practices for more than 30 years. Infusion services, once
      just a supportive service, grew exponentially in most practices between 1991 and
      2000, to the point at which revenue from these services created a high, which
      made all things possible, including care of underinsured or uninsured patients.
      This altered state was further enhanced in the early part of this past decade
      when the introduction of high-cost chemotherapeutics and biologic agents created
      the euphoria of big business and a true dollar distortion for even the smallest
      oncology practice. RESULTS: In 2005, government and payer intervention forced
      average wholesale price to average sales price conversion to reduce the drug
      effect. Concurrently, payer scrutiny of utilization and medical necessity with
      further dose reductions, equating to margins, led many practices to experience
      painful drug withdrawal symptoms. Despite the enormous financial risk for
      unreimbursed expense and acknowledged spiraling decline of drug margins of
      greater than 30% since 2002, the seductive possibility of a financial fix keeps
      the practices hooked. CONCLUSION: Many practices will make poor financial choices
      and will gamble with their financial health by consuming precious resources to
      support the habit. We propose the drug test: Run your practice financials without
      drugs. Can you cover the total practice expense without drugs? If not, determine
      your level of dependency on the drug margin, and adjust your service lines and
      salaries accordingly. We issue the following warning: Drug dependencies may be
      hazardous to the financial health of your organization.

PMID- 29447094
TI  - Reduction in Chemotherapy Mixing Errors Using Six Sigma: Illinois CancerCare
      Experience.
AB  - PURPOSE: Chemotherapy mixing errors (CTMRs), although rare, have serious
      consequences. Illinois CancerCare is a large practice with multiple satellite
      offices. The goal of this study was to reduce the number of CTMRs using Six Sigma
      methods. PATIENTS AND METHODS: A Six Sigma team consisting of five participants
      (registered nurses and pharmacy technicians [PTs]) was formed. The team had 10
      hours of Six Sigma training in the DMAIC (ie, Define, Measure, Analyze, Improve,
      Control) process. Measurement of errors started from the time the CT order was
      verified by the PT to the time of CT administration by the nurse. Data collection
      included retrospective error tracking software, system audits, and staff surveys.
      RESULTS: Root causes of CTMRs included inadequate knowledge of CT mixing
      protocol, inconsistencies in checking methods, and frequent changes in staffing
      of clinics. Initial CTMRs (n = 33,259) constituted 0.050%, with 77% of these
      errors affecting patients. The action plan included checklists, education, and
      competency testing. The postimplementation error rate (n = 33,376, annualized)
      over a 3-month period was reduced to 0.019%, with only 15% of errors affecting
      patients. Initial Sigma was calculated at 4.2; this process resulted in the
      improvement of Sigma to 5.2, representing a 100-fold reduction. Financial
      analysis demonstrated a reduction in annualized loss of revenue (administration
      charges and drug wastage) from $11,537.95 (Medicare Average Sales Price) before
      the start of the project to $1,262.40. CONCLUSION: The Six Sigma process is a
      powerful technique in the reduction of CTMRs.

PMID- 29447095
TI  - Quantitative Analysis of Operating Room Inventory Management Practices at a
      Tertiary Cancer Center.
AB  - PURPOSE: In Ontario, health care spending has grown to 45% of total government
      expenditures. In a public health care system, changes in demographics and the
      emergence of innovative technologies challenge our ability to adapt to evolving
      patient needs. To maintain a high standard of clinical effectiveness, there is a
      need to identify opportunities to improve health care delivery. This study was
      structured to meet the following objectives: to understand the operating room
      (OR) inventory practices at a tertiary academic hospital, to mathematically model
      this process to ascertain service levels based on changes in inventory and
      demand, and to define the appropriate level of reusable inventory for open and
      laparoscopic colorectal surgery. METHODS: We retrospectively reviewed OR
      throughput for all cases of colorectal cancer from January 1, 2010, to January
      31, 2011. The process flow of OR instrumentation was studied to understand delays
      in the provision of inventory. Combining total surgeries performed with surgeon
      specific instrument preferences generated daily instrument demand. We fitted
      parametric demand distributions for two instrument sets for major colon
      resections. Markovian models were used to estimate the distribution of available
      inventory and the likelihood of insufficient instruments on any given day.
      RESULTS: We reviewed 1,458 cases, 39.5% of which involved major open surgery,
      whereas 26.2% involved laparoscopic surgery. Demand for open and laparoscopic
      instrument sets was observed to fit binomial (20, 0.15) and Poisson (1.41)
      distributions, respectively. On the basis of these curves, we estimated the
      probability distribution of the in-stock inventory and, subsequently, the
      probability that demand would exceed supply on any given day ( Table 1 ). In
      particular, with 10 open and six laparoscopic sets currently owned by the
      institution, the probabilities that there would be insufficient inventory were
      3.02% and 2.17%, respectively. [Table: see text] Conclusion: This analysis will
      guide purchasing decisions based on desired service levels and forecasted changes
      in demand. Furthermore, by ensuring that demand is being serviced, this analysis
      will help to curb loss of revenue, decrease wait times, and limit potential
      patient morbidity. Strategic purchasing can also reduce excessive inventory and
      therefore minimize shrinkage and obsolescence and increase working capital and
      institutional flexibility.

PMID- 29447096
TI  - Countering the Misincentivization of Cancer Medicine by Real-Time Personal
      Professional Education.
AB  - PURPOSE: In the United States, public and private payer misincentivization of
      medical care and the invisibility of costs to the consumers of that care have
      conspired to create unsustainable growth in health care expenditure that
      undermines our economy, diminishes our productivity, and limits our international
      competitiveness. Cancer medicine provides a small yet salient example. On
      average, Medicare reimburses oncologists 6% above the average acquisition price
      for essential anticancer agents and supportive therapies. The costs of these
      agents vary across a stunning five orders of magnitude, from a few dollars to
      more than $400,000 per course of treatment. The profitability to providers varies
      across approximately four orders of magnitude, from cents to thousands of dollars
      per treatment. National guidelines (National Comprehensive Cancer Network [NCCN],
      American Society of Clinical Oncology [ASCO]) help providers select the most
      effective therapies without regard for cost. METHODS: We created an oncologist-to
      oncologist professional education program to help cancer physicians optimally use
      expensive long-acting white blood cell growth factors, in accordance with these
      national guidelines. We then compared their use across a population of
      approximately 97,000 Medicare members before and after our intervention. Baseline
      use was recorded over two consecutive quarters (2009 to 2010). In March 2010, our
      oncologists initiated real-time discussions with the oncologists of 22 separate
      groups if these agents were ordered for use with regimens that placed patients at
      less than 10% risk of febrile neutropenia, according to NCCN guidelines. Neither
      NCCN nor ASCO recommend the routine use of these agents in this low-risk group.
      The care of 82 such patients was thoroughly discussed in the following 6 months.
      RESULTS: The monthly costs for these agents decreased by more than 50% by the
      final month of our intervention, although savings began immediately, reducing
      costs by more than $150,000 per quarter. No episode of febrile neutropenia was
      recorded in any patient in the intervention group. These savings generalize to
      the entire Medicare population at $30 million each month. CONCLUSION: We conclude
      that personal, oncologist-to-oncologist, real-time professional education will
      favorably modify oncologic prescribing behavior and can do so with significant
      immediate savings at no risk to patients with cancer.

PMID- 29447097
TI  - Wise Investment? Modeling Industry Profitability and Risk of Targeted
      Chemotherapy for Incurable Solid Cancers.
AB  - PURPOSE: Pharmaceutical development involves substantial financial risk. This
      risk, rising development costs, and the promotion of continued research and
      development have been cited as major drivers in the progressive increase in drug
      prices. Currently, cost-effective analyses are being used to determine the value
      of treatment. However, cost-effective analyses practically function as a
      threshold for value and do not directly address the rationale for drug prices. We
      set out to create a functional model for industry price decisions and clarify the
      minimum acceptable profitability of new drugs. METHODS: Assuming that industry
      should only invest in profitable ventures, we employed a linear cost-volume
      profit breakeven analysis to equate initial capital investment and risk and post
      drug-approval profits, where drug development represents the bulk of investment.
      A Markov decision analysis model was also used to define the relationships
      between investment events risk. A systematic literature search was performed to
      determine event probabilities, clinical trial costs, and total expenses as inputs
      into the model. Disease-specific inputs, current market size across regions, and
      lengths of treatment for cancer types were also included. RESULTS: With
      development of single novel chemotherapies costing from $802 to $1,042 million
      (2002 US dollars), pharmaceutical profits should range from $4.3 to $5.2 billion,
      with an expected rate of return on investment of 11% annually. However,
      diversification across cancer types for chemotherapy can reduce the minimum
      required profit to less than $3 billion. For optimal diversification, industry
      should study four tumor types per drug; however, nonprofit organizations could
      tolerate eight parallel development tracks to minimize the risk of development
      failure. Assuming that pharmaceutical companies hold exclusive rights for drug
      sales for only 5 years after market approval, the minimum required profit per
      drug per month per patient ranges from $294 for end-stage lung cancer to $3,231
      for end-stage renal cell carcinoma. CONCLUSION: Pharmaceutical development in
      oncology is costly, with substantial risk, but is also highly profitable. Minimum
      acceptable profits per drug per month of treatment per patient vary with
      prevalence of disease, but they should be less than $5,000 per month of treatment
      in the developed world. Minimum acceptable profits may be lower for treatments
      with additional efficacy in the earlier stages of a tumor type. However, this
      type of event could not be statistically modeled.

PMID- 29447098
TI  - Achieving Meaningful Use and Operational Efficiency.
AB  - PURPOSE: The Centers for Medicare and Medicaid Services (CMS), through the
      Electronic Health Record (EHR) Incentive Program, are providing incentive
      payments to eligible professionals as they demonstrate meaningful use of
      certified EHR technology. Eligible professionals can receive up to $44,000 over a
      5-year period for Medicare participation if they successfully demonstrate the
      ability to automatically generate, transmit, and meet thresholds for specific
      reporting elements from the EHR. Meeting the meaningful use requirement involves
      a reorganization of workflow within the clinical setting so that the data
      elements necessary to produce the relevant measurements are documented in the
      electronic medical record (EMR) as they are delivered. A by-product of this is
      operational efficiency improvement in three areas: coordination of data input
      throughout the care team to reduce or remove bottlenecks, assignment of
      responsibility for specific activity, and real-time objective monitoring of the
      work process. METHODS: Using the reporting system functionality of a certified
      EMR deployed in a two-physician medical oncology practice at the New London
      Cancer Center, the objective measurement of the ability of each of the eligible
      providers in the clinic to improve their individual MU scores was tracked.
      Analysis of the progress of each provider revealed gaps. Process issues were
      identified by work group: secretaries, laboratory preparation and phlebotomy
      staff, nurses, and clinicians. The designated physician leader met with each
      group to discuss the sections relevant to that particular group. RESULTS: By
      discovering and addressing work processes that were not utilizing the ability of
      the EHR to capture and document (ie, meaningful use of the EHR), rapid progress
      that affected all of the eligible providers and all patients cared for was made.
      Changes resulted in increased clarity of clinical and administrative
      responsibilities during patient processing and clinical care provision.
      Meaningful use attestation was completed in 14 weeks. CONCLUSION: Completion of
      the documentation necessary to meet the requirements of the EHR Incentive Program
      led to the discovery of systemic inefficiencies in administrative and clinical
      workflows. Addressing these bottlenecks, along with using the reporting
      capability of the EHR to measure the impact of workflow changes, enabled the
      administrative and care teams to make changes quickly and effectively. The
      certified EHR provided guidance and status-reporting capabilities that allowed
      the practice to achieve the meaningful use requirement.

PMID- 29447099
TI  - Keeping Pace With Oral Chemotherapy.
AB  - PURPOSE: Although the rising number of oral chemotherapy agents offers many
      patients with cancer a more convenient and less invasive treatment option
      compared with infusion therapy, multiple risks and challenges have been
      identified with the oral regimen, including dosing errors, drug interactions, and
      nonadherence or overadherence. Until recently, cancer care providers had
      maintained a considerable amount of control, including the certainty that the
      right drug was being administered in the right dose, via the right route, at the
      right time, and to the right patient-all of which were meticulously documented in
      patient records. In contrast, oral chemotherapy takes much of the control out of
      the clinician's hands and places tremendous responsibility on the patient,
      raising a number of adherence and control issues. Studies regarding oral hormonal
      therapy for breast cancer have described adherence rates ramping down from 83% to
      77% within the first 2 years of therapy. These figures continue to decrease over
      time to a range of 50% to 64% within 4 to 5 years. On the basis of these data and
      a literature review, we developed a program to promote adherence to oral
      anticancer protocols. METHODS: Our team took a proactive, team-focused approach
      and established protocols at a time when oral chemotherapies were still at a low
      volume. In addition to infrastructures, policies, and procedures promoting
      collaborative communications among physicians, nurses, and pharmacists, we
      developed an in-depth educational component that provides the linchpin for
      ensuring an effective oral chemotherapy program. Our program focuses on three key
      pillars: education, communication, and follow-up. Our project team first
      conducted an inclusive review of available literature, with the objective of
      designing processes that would help our program directly address existing risks
      and challenges. Then we introduced concepts for the formalized program to our
      cancer center physicians, whose support was paramount to successful
      implementation. The next step was to start the program with a mandatory in
      service for all clinical staff, which included a presentation of the research
      evidence that prompted the creation of this model for oral chemotherapy. To
      enhance patient understanding, our team provides printed materials,
      individualized calendars, and in some cases preloaded pillboxes to assist
      patients. Concurrently, our nurses provide weekly telephone intervention for the
      second and third months and monthly phone interventions thereafter. Communication
      is key to the success of the program. This includes the use of a translation
      service to ensure effective communication with all non-English-speaking patients.
      We intervene early for those patients with financial barriers and offer a variety
      of referrals and resources for emotional, nutritional, and patient support
      services, including transportation issues. RESULTS: Since the inception of the
      program, the in-service has been incorporated into our new employee orientation.
      At the same time, a growing number of cancer center physicians are embracing the
      program. The program has received the attention of the Oncology Roundtable, which
      developed a Webinar around the topic, and been described in a feature article in
      an oncology journal. Finally, our team has been tapped to educate other
      pharmacists regarding oral agents, toxicity profiles, and safe handling.
      CONCLUSION: By combining safeguards, patient education strategies, intensive
      follow-up, and a system of effective checks and balances, our center is taking
      significant steps to maximize patient safety and oral chemotherapy treatment
      effectiveness, while keeping pace with the rapidly occurring changes in oncology
      practice.

PMID- 29447100
TI  - Extending Oncology Clinical Services to Rural Areas of Texas Via Teleoncology.
AB  - : Abstracts Purpose: For patients in rural Texas, accessing cancer specialists is
      quite challenging. Texas has many remote areas without community-based cancer
      care, requiring patients to travel long distances for specialized cancer
      professional consultations and services. An anticipated shortage of medical
      oncology expertise will exacerbate this situation. The advent of telemedicine
      tools has created an opportunity to easily extend specialized cancer services to
      underserved populations of patients with cancer in Texas. However, more research
      is needed to explore how well telemedicine tools will be accepted and used by
      both patients and oncologists alike. Data suggesting that teleoncology services
      are well accepted and liked by patients and health care professionals would
      provide a basis for expanding this method of delivering care. If effective,
      telemedicine tools could help patients with cancer in rural Texas, and throughout
      the United States, access the same quality of cancer care as their counterparts
      living in urban areas. METHODS: This pilot study will compare the effectiveness
      and reliability of remote oncologic clinical evaluations conducted via a
      telemedicine application with the traditional method of onsite evaluations in a
      private practice setting in rural East Texas. Patient and physician satisfaction
      with the clinical consultations and their perceptions of the telemedicine
      application will be assessed using a questionnaire administered at the conclusion
      of the clinical meetings. RESULTS: Initial results indicate high patient and
      physician satisfaction scores as well as high reliability and adequacy of the
      equipment and technology being used. CONCLUSION: Both patients and physicians are
      highly satisfied with the quality of teleoncology examinations and express
      openness to this method of delivering care.

PMID- 29447101
TI  - Development by a Large Integrated Health Care System of an Objective Methodology
      for Evaluation of Medical Oncology Service Sites.
AB  - PURPOSE: Aurora Health Care (AHC) is the largest health care system in Wisconsin,
      with 14 acute care hospitals. In early 2010, a group of 18 medical oncologists
      became affiliated with AHC. This affiliation added 13 medical oncology infusion
      clinics to our existing 12 sites. In the era of health care reform and declining
      reimbursement, we need an objective method and criteria to evaluate our 25
      outpatient medical oncology sites. We developed financial, clinical, and
      strategic tools for the evaluation and management of our cancer subservice lines
      and outpatient sites. The key to our success has been the direct involvement of
      stakeholders with a vested interest in the services in the selection of the
      criteria and evaluation process. METHODS: We developed our objective metrics for
      evaluation based on strategic, financial, operational, and patient experience
      criteria. Strategic criteria included: population trends, full-time equivalent
      (FTE) medical oncologists/primary care physicians, FTE radiation oncologists, FTE
      oncologic surgeons, new annual cases of patients with cancer, and market share
      trends. Financial criteria per site included: physician work relative value
      units, staff FTE by type, staff salaries, and profit and loss. Operational
      criteria included: facility by type (clinic v hospital based), hours of
      operation, and facility detail (eg, No. of chairs, No. of procedure and
      examination rooms, square footage). Patient experience criteria included: nursing
      model primary/nurse navigators, multidisciplinary support at site, Press Ganey
      (South Bend, IN; health care performance improvement company) results, and
      employee engagement score. RESULTS: The outcome of our data analysis has resulted
      in the development of recommendations for AHC senior leadership and geographic
      market leadership to consider the consolidation of four sites (phase one, four
      sites; phase two, two sites) and priority strategic sites to address capacity
      issues that limit growth. The recommendations if implemented would result in
      significant cost savings, currently being quantified as a result of consolidation
      and improved efficiency. A reinvestment of these cost savings would be required
      to address facility expansion and program enhancement to maximize patient
      centered expert care consistently across all of our remaining sites of service.

PMID- 29447102
TI  - 2012 Electronic Prescribing Incentive Program.

PMID- 29447103
TI  - Blood sample contamination by glucose-containing solutions: effects and
      identification.

PMID- 29447104
TI  - Non-beta-haemolytic variants of Streptococcus pyogenes: a challenge for the
      microbiology laborator.

PMID- 29447105
TI  - Multi-muscle electrical stimulation and stand training: Effects on standing.
AB  - OBJECTIVE: To examine the biomechanical and neuromuscular effects of a
      longitudinal multi-muscle electrical stimulation (submaximal intensities)
      training of the lower limbs combined with/without activity-based stand training,
      on the recovery of stability and function for one individual with spinal cord
      injury (SCI). DESIGN: Single-subject, longitudinal study. SETTING:
      Neuroplasticity laboratory. PARTICIPANT: A 34-year-old male, with sensory- and
      motor-complete SCI (C5/C6). INTERVENTIONS: Two consecutive interventions: 61
      hours of supine, lower-limb ES (ES-alone) and 51 hours of ES combined with stand
      training using an overhead body-weight support system (ST + ES). OUTCOME
      MEASURES: Clinical measures, trunk stability, and muscle activity were assessed
      and compared across time points. Trunk Stability Limit (TSL) determined
      improvements in trunk independence. RESULTS: Functional clinical values increased
      after both interventions, with further increases post ST + ES. Post ES-alone,
      trunk stability was maintained at 81% body-weight (BW) loading before failure;
      post ST + ES, BW loading increased to 95%. TSL values decreased post ST + ES
      (TSLA/P=54.0 kg.cm, TSLM/L=14.5 kg.cm), compared to ES-alone (TSLA/P=8.5 kg.cm,
      TSLM/L=3.9 kg.cm). Trunk muscle activity decreased post ST + ES training,
      compared to ES-alone. CONCLUSION: Neuromuscular and postural trunk control
      dramatically improved following the multi-muscle ES of the lower limbs with stand
      training. Multi-muscle ES training paradigm of the lower limb, using traditional
      parameters, may contribute to the functional recovery of the trunk.

PMID- 29447107
TI  - Vitamin D status and risk of dementia and Alzheimer's disease: A meta-analysis of
      dose-response.
AB  - OBJECTIVE: We aimed to test the dose-response association of serum 25(OH)D and
      risk of dementia and Alzheimer's disease (AD). METHODS: We performed a systematic
      search of PubMed and Scopus from database inception up to September 2017.
      Longitudinal cohort studies reporting risk estimates of incident dementia or AD
      in the general population, and for three or more quantitative categories of serum
      25(OH)D were included. Pooled hazard ratios (HRs) were calculated using fixed
      effects/random-effects models. RESULTS: Seven prospective cohort studies and one
      retrospective cohort study (total n = 28,354) involving 1953 cases of dementia
      and 1607 cases of AD were included. The pooled HRs of dementia and AD were 1.09
      (95%CI: 0.95, 1.24) and 1.19 (95%CI: 0.96, 1.41) for vitamin D insufficiency (10
      20 ng/ml), and 1.33 (95%CI: 1.08, 1.58) and 1.31 (95%CI: 0.98, 1.65) for
      deficiency (<10 ng/ml), respectively. The lower risk of dementia was observed at
      serum 25(OH)D of ~25 ng/ml, whereas the risk of AD decreased continuously along
      with the increase of serum 25(OH)D up to ~35 ng/ml. CONCLUSION: Higher levels of
      serum 25(OH)D was associated with a lower risk of dementia and AD, but we have no
      conclusive evidence regarding serum 25(OH)D levels of >35 ng/ml.

PMID- 29447108
TI  - Introducing a simple model system for binding studies of known and novel
      inhibitors of AMPK: a therapeutic target for prostate cancer.
AB  - Prostate cancer (PC) is one of the leading cancers in men, raising a serious
      health issue worldwide. Due to lack of suitable biomarker, their inhibitors and
      the platform for testing those inhibitors result in poor prognosis of PC. AMP
      activated protein kinase (AMPK) is a highly conserved protein kinase found in
      eukaryotes that is involved in growth and development, and also acts as a
      therapeutic target for PC. The aim of the present study is to identify novel
      potent inhibitors of AMPK and propose a simple cellular model system for
      understanding its biology. Structural modelling and MD simulations were performed
      to construct and refine the 3D models of Dictyostelium and human AMPK. Binding
      mechanisms of different drug compounds were studied by performing molecular
      docking, molecular dynamics and MM-PBSA methods. Two novel drugs were isolated
      having higher binding affinity over the known drugs and hydrophobic forces that
      played a key role during protein-ligand interactions. The study also explored the
      simple cellular model system for drug screening and understanding the biology of
      a therapeutic target by performing in vitro experiments.

PMID- 29447106
TI  - Challenges of site-specific selenocysteine incorporation into proteins by
      Escherichia coli.
AB  - Selenocysteine (Sec), a rare genetically encoded amino acid with unusual chemical
      properties, is of great interest for protein engineering. Sec is synthesized on
      its cognate tRNA (tRNASec) by the concerted action of several enzymes. While all
      other aminoacyl-tRNAs are delivered to the ribosome by the elongation factor Tu
      (EF-Tu), Sec-tRNASec requires a dedicated factor, SelB. Incorporation of Sec into
      protein requires recoding of the stop codon UGA aided by a specific mRNA
      structure, the SECIS element. This unusual biogenesis restricts the use of Sec in
      recombinant proteins, limiting our ability to study the properties of
      selenoproteins. Several methods are currently available for the synthesis
      selenoproteins. Here we focus on strategies for in vivo Sec insertion at any
      position(s) within a recombinant protein in a SECIS-independent manner: (i)
      engineering of tRNASec for use by EF-Tu without the SECIS requirement, and (ii)
      design of a SECIS-independent SelB route.

PMID- 29447109
TI  - Sepsis 2018: Definitions and Guideline Changes.
AB  - BACKGROUND: Sepsis is a global healthcare issue and continues to be the leading
      cause of death from infection. Early recognition and diagnosis of sepsis is
      required to prevent the transition into septic shock, which is associated with a
      mortality rate of 40% or more. DISCUSSION: New definitions for sepsis and septic
      shock (Third International Consensus Definitions for Sepsis and Septic Shock
      [Sepsis-3]) have been developed. A new screening tool for sepsis (quick
      Sequential Organ Failure Assessment [qSOFA]) has been proposed to predict the
      likelihood of poor outcome in out-of-intensive care unit (ICU) patients with
      clinical suspicion of sepsis. The Surviving Sepsis Campaign Guidelines were
      recently updated and include greater evidence-based recommendations for treatment
      of sepsis in attempts to reduce sepsis-associated mortality. This review
      discusses the new Sepsis-3 definitions and guidelines.

PMID- 29447110
TI  - Time- and polarity-dependent proteomic changes associated with homeostatic
      scaling at central synapses.
AB  - In homeostatic scaling at central synapses, the depth and breadth of cellular
      mechanisms that detect the offset from the set-point, detect the duration of the
      offset and implement a cellular response are not well understood. To understand
      the time-dependent scaling dynamics we treated cultured rat hippocampal cells
      with either TTX or bicucculline for 2 hr to induce the process of up- or down
      scaling, respectively. During the activity manipulation we metabolically labeled
      newly synthesized proteins using BONCAT. We identified 168 newly synthesized
      proteins that exhibited significant changes in expression. To obtain a temporal
      trajectory of the response, we compared the proteins synthesized within 2 hr or
      24 hr of the activity manipulation. Surprisingly, there was little overlap in the
      significantly regulated newly synthesized proteins identified in the early- and
      integrated late response datasets. There was, however, overlap in the functional
      categories that are modulated early and late. These data indicate that within
      protein function groups, different proteomic choices can be made to effect early
      and late homeostatic responses that detect the duration and polarity of the
      activity manipulation.

PMID- 29447112
TI  - Evidence that cell surface localization of serine protease activity facilitates
      cleavage of the protease activated receptor CDCP1.
AB  - The cellular receptor CUB domain containing protein 1 (CDCP1) is commonly
      elevated and functionally important in a range of cancers. CDCP1 is cleaved by
      serine proteases at adjacent sites, arginine 368 (R368) and lysine 369 (K369),
      which induces cell migration in vitro and metastasis in vivo. We demonstrate that
      membrane localization of serine protease activity increases efficacy of cleavage
      of CDCP1, and that both secreted and membrane anchored serine proteases can have
      distinct preferences for cleaving at CDCP1-R368 and CDCP1-K369. Approaches that
      disrupt membrane localization of CDCP1 cleaving serine proteases may interfere
      with the cancer promoting effects of CDCP1 proteolysis.

PMID- 29447113
TI  - The AGO proteins: an overview.
AB  - Small RNAs govern almost every biological process in eukaryotes associating with
      the Argonaute (AGO) proteins to form the RNA-induced silencing complex (mRISC).
      AGO proteins constitute the core of RISCs with different members having variety
      of protein-binding partners and biochemical properties. This review focuses on
      the AGO subfamily of the AGOs that are ubiquitously expressed and are associated
      with small RNAs. The structure, function and role of the AGO proteins in the cell
      is discussed in detail.

PMID- 29447111
TI  - Free light chains of immunoglobulins in patients with systemic sclerosis:
      correlations with lung involvement and inflammatory milieu.
AB  - AIM: Humoral immunity and B cells are thought to play an important role in the
      pathophysiology of the systemic sclerosis (SSc). The production of free light
      chains (FLC) of immunoglobulins is abnormally high in several pathological
      autoimmune conditions and reflects B cell activation. Furthermore, FLCs
      demonstrated different biological activities including their capability to
      modulate the immune system, proteolytic activity and complement cascade
      activation. The aims of this study are to determine the FLC levels in patients
      with SSc compared with healthy controls (HC) and to study their possible
      association with organ involvement and disease characteristics. METHODS: Sixty
      five patients with SSc and 20 HC were studied. Clinical and immunological
      inflammatory characteristics were assessed for all the patients with SSc. kappa
      FLC and lambda-FLC, interleukin 6 (IL-6) and B cell activating factor levels were
      measured. RESULTS: The mean serum kappa-FLC levels and FLC ratio were
      significantly higher in patients with SSc compared with HC, while the serum
      lambda-FLC levels were comparable.The levels of FLC were comparable in patients
      with diffuse skin disease and limited skin involvement, while kappa-FLC levels
      were increased in patients with restrictive lung (forced vital capacity (FVC)
      <80%) disease (26.4+/-7.4 mg/L) when compared with patients with FVC >=80%
      (19.6+/-7.3 mg/L, P=0.009). In patients with SSc, the levels of serum kappa-FLC
      level directly correlated with the IL-6 levels (R=0.3, P=0.001) and disease
      activity (R=0.4, P=0.003). CONCLUSIONS: FLC levels are elevated in SSc and high
      levels are associated with lung involvement and with a higher degree of
      inflammation, supporting a possible role of B cell activation in the
      pathophysiology of the disease.

PMID- 29447114
TI  - Higher D-lactate levels are associated with higher prevalence of small dense low
      density lipoprotein in obese adolescents.
AB  - BACKGROUND: Childhood obesity is associated with insulin resistance (IR),
      increased levels of small dense low-density lipoprotein (sd-LDL) as well as with
      augmented hepatic de novo lipogenesis, which implies increased triose phosphate
      fluxes that may lead to increased methylglyoxal (MG) and its catabolic end
      product D-lactate. We hypothesized that obese adolescents have increased D
      lactate serum levels associated with high incidence of sd-LDL. METHODS: This is a
      cross-sectional study where the anthropometric characteristics, atherogenic
      dyslipidemia complex, sd-LDL (Lipoprint, Quantimetrix) and D-lactate (kinetic
      enzymatic analysis) were explored in 30 lean vs. 30 obese adolescents (16 females
      and 14 males per group) without metabolic syndrome (MetS). Endothelial function
      by flow-mediated dilation (FMD, by ultrasound) and arterial lesion by carotid
      intima media thickness (CIMT, by ultrasound) were also measured. RESULTS: The
      mean age of participants was 16.8 +/- 1.4 years. Obese adolescents had a body
      mass index of 32.7 +/- 3.8 vs. 21.8 +/- 2.1 in lean participants. The obesity
      group showed higher D-lactate levels: 6.2 +/- 3.0 vs. 4.5 +/- 2.5 MUmol/L, higher
      levels of insulin: 15 (9.6-23.5) vs. 7.9 (6.5-10.5) MUIU/mL; triglyceride (TG):
      1.46 (1.1-1.8) vs. 0.84 (0.6-1.2) mmol/L; non-high-density lipoprotein
      cholesterol (NON-HDL-C): 2.8 +/- 0.9 vs. 2.3 +/- 0.7 mmol/L; total cholesterol
      (TC)/HDL-C) index: 2.9 +/- 0.7 vs. 2.4 +/- 0.5; TG/HDL-C index: 2.2 (1.5-2.8) vs.
      1.1 (0.8-1.8); %LDL-3: 4.2 +/- 4.07 vs. 1.9 +/- 2.7; smaller LDL size: 270.6 +/-
      3 vs. 272.2 +/- 1.1 A. D-lactate correlated positively with LDL-2: r = 0.44 and
      LDL-3 (sd-LDL): r = 0.49 and negatively with large LDL-1: r = -0.48 and LDL size:
      r = -0.46; (p<0.05, p<0.01, p<0.001 and p<0.0001, respectively). Obese
      adolescents showed higher CIMT: 0.51 +/- 0.08 vs. 0.46 +/- 0.08 mm and lower FMD:
      20.3% +/- 6.7% vs. 26.0% +/- 9.3%. CONCLUSIONS: Obese adolescents display
      subclinical signs of IR and endothelial dysfunction. Higher serum sd-LDL levels
      correlated positively with D-lactate levels. These findings suggest an
      association between atherogenic dyslipoproteinemia and whole body MG fluxes
      already detectable in apparently healthy obese adolescents.

PMID- 29447115
TI  - Anti-streptavidin antibodies mimicking heterophilic antibodies in thyroid
      function tests.

PMID- 29447116
TI  - Amyloid toxicity in Alzheimer's disease.
AB  - A major feature of Alzheimer's disease (AD) pathology is the plaque composed of
      aggregated amyloid-beta (Abeta) peptide. Although these plaques may have harmful
      properties, there is much evidence to implicate soluble oligomeric Abeta as the
      primary noxious form. Abeta oligomers can be generated both extracellularly and
      intracellularly. Abeta is toxic to neurons in a myriad of ways. It can cause pore
      formation resulting in the leakage of ions, disruption of cellular calcium
      balance, and loss of membrane potential. It can promote apoptosis, cause synaptic
      loss, and disrupt the cytoskeleton. Current treatments for AD are limited and
      palliative. Much research and effort is being devoted to reducing Abeta
      production as an approach to slowing or preventing the development of AD. Abeta
      formation results from the amyloidogenic cleavage of human amyloid precursor
      protein (APP). Reconfiguring this process to disfavor amyloid generation might be
      possible through the reduction of APP or inhibition of enzymes that convert the
      precursor protein to amyloid.

PMID- 29447117
TI  - On the high-lift characteristics of a bio-inspired, slotted delta wing.
AB  - A bio-inspired, slotted delta wing was abstracted from a multi-vane propulsor
      geometry ubiquitous in nature, and analysed to investigate aerodynamic
      performance during acceleratory and steady-state motions. Evolutionary
      convergence of slotted geometries in nature suggests an aerodynamic benefit in
      manoeuvrability, as exemplified in the fins and wings of a broad range of extant
      and extinct swimmers and flyers, respectively. Through direct force measurements
      and stereoscopic particle image velocimetry, it was found that the abstracted,
      slotted geometry exhibited a region of steady-state lift and drag enhancement at
      angles of attack greater than 25 degrees  when compared to a reference profile
      based on a delta-wing plate. At an angle of attack of 30 degrees , the lift and
      drag measured on the abstracted model were 15.3% and 17.0% higher than the delta
      wing model, respectively. In contrast, these shapes showed little difference in
      performance during an acceleration-from-rest manoeuvre. It was found that the
      secondary and tertiary vanes of the abstraction encouraged the formation of
      additional leading-edge vorticity. The formation of these additional leading-edge
      vortices was confirmed by an increase in streamwise circulation measured near
      each effective leading edge along the length of the chord. As such, this
      configuration provides lift augmentation appropriate for the development of high
      performance control surfaces.

PMID- 29447118
TI  - Fluorescence properties of Yb3+-Er3+ co-doped phosphate glasses containing silver
      nanoparticles.
AB  - Er3+-Yb3+ co-doped phosphate glasses containing silver nitrate (SN), were
      fabricated. Transmission electron microscopy (TEM) and x-ray photoelectron
      spectroscopy (XPS) analyses were used to evidence the nucleation and presence of
      silver nanoparticles (SNP). The basic parameters of the glasses were inspected by
      means of absorption and fluorescence spectra, and fluorescence lifetimes under
      excitation at 916 nm (in-band of Yb3+), and at 406 nm (in-band of surface plasmon
      resonance given by the presence of SNP). The spectra as well as estimates for the
      basic parameters defining the lasing/amplifying potential of the glasses were
      studied as a function of SN concentration. The experimental results indicate that
      by increasing the SN content an enhancement of Er3+/Yb3+ fluorescence takes
      place.

PMID- 29447119
TI  - Pharmacological approach to increasing the retention of radiation-induced gamma
      H2AX foci using phosphatase inhibitors: significance in radiation biodosimetry.
AB  - In a scenario of accidental mass radiation exposure transportation and analysis
      of samples may take some time, resulting in loss of biomarker information over
      this period. The present study aims to use phosphatase inhibitors for longer
      retention of focal signals to adopt gamma-H2AX as a biodosimetric biomarker for
      the management of early triage. Peripheral blood lymphocytes isolated from
      healthy individuals were irradiated in vitro with x-rays and gamma-H2AX foci were
      analysed using fluorescent microscopy and flow cytometric methods. Further, the
      effect of protein phosphatase 2A inhibitors such as calyculin A, fostriecin and
      okadiac acid on the retention of foci was studied. Fluorescent microscopy was
      found to be a more sensitive method than flow cytometry. Calyculin A showed
      significant retention of focal signals at 6 h with 1.5-fold increased retention
      compared to radiation alone; this may prove beneficial in early triage management
      because of a better dose approximation.

PMID- 29447120
TI  - Quasiparticle scattering in type-II Weyl semimetal MoTe2.
AB  - The electronic structure of type-II Weyl semimetal molybdenum ditelluride (MoTe2)
      is studied by using scanning tunneling microscopy and density functional theory
      calculations. Through measuring energy-dependent quasiparticle interference (QPI)
      patterns with a cryogenic scanning tunneling microscope, several characteristic
      features are found in the QPI patterns. Two of them arise from the Weyl semimetal
      nature; one is the topological Fermi arc surface state and the other can be
      assigned to be a Weyl point. The remaining structures are derived from the
      scatterings relevant to the bulk electronic states. The findings lead to further
      understanding of the topological electronic structure of type-II Weyl semimetal
      MoTe2.

PMID- 29447121
TI  - P3HT-graphene bilayer electrode for Schottky junction photodetectors.
AB  - We have investigated the effect of a poly (3-hexylthiophene-2.5-diyl)(P3HT)
      graphene bilayer electrode on the photoresponsivity characteristics of Si-based
      Schottky photodetectors. P3HT, which is known to be an electron donor and absorb
      light in the visible spectrum, was placed on CVD grown graphene by dip-coating
      method. The results of the UV-vis and Raman spectroscopy measurements have been
      evaluated to confirm the optical and electronic modification of graphene by the
      P3HT thin film. Current-voltage measurements of graphene/Si and P3HT-graphene/Si
      revealed rectification behavior confirming a Schottky junction formation at the
      graphene/Si interface. Time-resolved photocurrent spectroscopy measurements
      showed the devices had excellent durability and a fast response speed. We found
      that the maximum spectral photoresponsivity of the P3HT-graphene/Si photodetector
      increased more than three orders of magnitude compared to that of the bare
      graphene/Si photodetector. The observed increment in the photoresponsivity of the
      P3HT-graphene/Si samples was attributed to the charge transfer doping from P3HT
      to graphene within the spectral range between near-ultraviolet and near-infrared.
      Furthermore, the P3HT-graphene electrode was found to improve the specific
      detectivity and noise equivalent power of graphene/Si photodetectors. The
      obtained results showed that the P3HT-graphene bilayer electrodes significantly
      improved the photoresponsivity characteristics of our samples and thus can be
      used as a functional component in Si-based optoelectronic device applications.

PMID- 29447122
TI  - 18F-FDG production procedures as a source of eye lens exposure to radiation.
AB  - Decreasing the individual dose limit of exposure to ionizing radiation to the eye
      lenses means verifying the need for routine monitoring of the eye lenses of
      workers exposed to ionizing radiation, including those employed in facilities
      producing radiopharmaceuticals based on short-lived isotopes. This work analyzes
      the exposure of the eye lenses of employees of centers that produce the isotopes
      for positron emission tomography, in particular fluorine-18. It takes into
      account the employment structure and work system of the discussed centers,
      including in terms of changing the dose limit of exposure to the eye lenses. This
      work complements the paper by Wrzesien (2018 Australas. Phys. Eng. Sci. Med.
      submitted) , which focused on the exposure of workers' hands to ionizing
      radiation in radiopharmaceutical production centers. Measurements were carried
      out using high-sensitivity thermoluminescence detectors (LiF: Mg, Cu, P-MCP-N).
      The measurements covered 17 employees. Our results show that the highest values
      of personal dose equivalent Hp(3) were recorded for the 18F-FDG quality control
      personnel and nurses who injected the radiopharmaceutical in the patients. In the
      group of nurses, the maximum daily does Hp(3) reached a value close to 200 MUSv.
      For staff who performed the quality control of the 18F-FDG, the maximum daily
      dose of Hp(3) exceeded 200 MUSv. The estimated annual exposure of the eye lenses
      of workers in these two occupational groups may exceed the new dose limit (20
      mSv/year). Results of this study indicate the need for optimization of the
      procedures related to quality control of radiopharmaceuticals and the injection
      of 18F-FDG in patients.

PMID- 29447123
TI  - Fast and controlled fabrication of porous graphene oxide: application of AFM
      tapping for mechano-chemistry.
AB  - This paper describes a novel method to fabricate porous graphene oxide (PGO) from
      GO by exposure to oxygen plasma. Compared to other methods to fabricate PGO
      described so far, e.g. the thermal and steam etching methods, oxygen plasma
      etching method is much faster. We studied the development of the porosity with
      exposure time using atomic force microscopy (AFM). It was found that the
      development of PGO upon oxygen-plasma exposure can be controlled by tapping mode
      AFM scanning using a Si tip. AFM tapping stalls the growth of pores upon further
      plasma exposure at a level that coincides with the fraction of sp2 carbons in the
      GO starting material. We suggest that AFM tapping procedure changes the bond
      structure of the intermediate PGO structure, and these stabilized PGO structures
      cannot be further etched by oxygen plasma. This constitutes the first report of
      tapping AFM as a tool for local mechano-chemistry.

PMID- 29447124
TI  - Spin crossover and high spin filtering behavior in Co-Pyridine and Co-Pyrimidine
      molecules.
AB  - We present a theoretical study on a series of cobalt complexes, which are
      constructed with cobalt atoms and pyridine/pyrimidine rings, using density
      functional theory. We investigate the structural and electric transport
      properties of spin crossover (SCO) Co complex with two spin states, namely low
      spin configuration [LS] and high-spin configuration [HS]. Energy analyses of the
      two spin states imply that the SCO Co-Pyridine2 and Co-Pyrimidine2 complexes may
      display a spin transition process accompanied by a geometric modification driven
      by external stimuli. A nearly perfect spin filtering effect is observed in the Co
      Pyrimidine2 complex with [HS] state. In addition, we also discover the contact
      dependent transmission properties of Co-Pyridine2. These findings indicate that
      SCO Co complexes are promising materials for molecular spintronic devices.

PMID- 29447125
TI  - The digital revolution.

PMID- 29447126
TI  - Impact of orientation on dimensional accuracy of 3D-printed orthodontic models.

PMID- 29447127
TI  - CAD/CAM software for three-dimensional printing.

PMID- 29447128
TI  - Incorporating three-dimensional printing in orthodontics.

PMID- 29447129
TI  - Digital workflows in orthodontics.

PMID- 29447130
TI  - Virtually eliminating undercuts in Invisalign's ClinCheck.

PMID- 29447133
TI  - Computerised training improves cognitive performance in chronic pain: a
      participant-blinded randomised active-controlled trial with remote supervision.
AB  - Chronic pain is associated with reduced efficiency of cognitive performance, and
      few studies have investigated methods of remediation. We trialled a computerised
      cognitive training protocol to determine whether it could attenuate cognitive
      difficulties in a chronic pain sample. Thirty-nine adults with chronic pain (mean
      age = 43.3, 61.5% females) were randomised to an 8-week online course (3
      sessions/week from home) of game-like cognitive training exercises, or an active
      control involving watching documentary videos. Participants received weekly
      supervision by video call. Primary outcomes were a global neurocognitive
      composite (tests of attention, speed, and executive function) and self-reported
      cognition. Secondary outcomes were pain (intensity; interference), mood symptoms
      (depression; anxiety), and coping with pain (catastrophising; self-efficacy).
      Thirty participants (15 training and 15 control) completed the trial. Mixed model
      intention-to-treat analyses revealed significant effects of training on the
      global neurocognitive composite (net effect size [ES] = 0.43, P = 0.017), driven
      by improved executive function performance (attention switching and working
      memory). The control group reported improvement in pain intensity (net ES = 0.65,
      P = 0.022). Both groups reported subjective improvements in cognition (ES = 0.28,
      P = 0.033) and catastrophising (ES = 0.55, P = 0.006). Depression, anxiety, self
      efficacy, and pain interference showed no change in either group. This study
      provides preliminary evidence that supervised cognitive training may be a viable
      method for enhancing cognitive skills in persons with chronic pain, but transfer
      to functional and clinical outcomes remains to be demonstrated. Active control
      results suggest that activities perceived as relaxing or enjoyable contribute to
      improved perception of well-being. Weekly contact was pivotal to successful
      program completion.

PMID- 29447131
TI  - DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade.
AB  - Synthetic lethality is an efficient mechanism-based approach to selectively
      target DNA repair defects. Excision repair cross-complementation group 1 (ERCC1)
      deficiency is frequently found in non-small-cell lung cancer (NSCLC), making this
      DNA repair protein an attractive target for exploiting synthetic lethal
      approaches in the disease. Using unbiased proteomic and metabolic high-throughput
      profiling on a unique in-house-generated isogenic model of ERCC1 deficiency, we
      found marked metabolic rewiring of ERCC1-deficient populations, including
      decreased levels of the metabolite NAD+ and reduced expression of the rate
      limiting NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT).
      We also found reduced NAMPT expression in NSCLC samples with low levels of ERCC1.
      These metabolic alterations were a primary effect of ERCC1 deficiency, and caused
      selective exquisite sensitivity to small-molecule NAMPT inhibitors, both in vitro
      - ERCC1-deficient cells being approximately 1,000 times more sensitive than ERCC1
      WT cells - and in vivo. Using transmission electronic microscopy and functional
      metabolic studies, we found that ERCC1-deficient cells harbor mitochondrial
      defects. We propose a model where NAD+ acts as a regulator of ERCC1-deficient
      NSCLC cell fitness. These findings open therapeutic opportunities that exploit a
      yet-undescribed nuclear-mitochondrial synthetic lethal relationship in NSCLC
      models, and highlight the potential for targeting DNA repair/metabolic crosstalks
      for cancer therapy.

PMID- 29447132
TI  - Role of GPCR (mu-opioid)-receptor tyrosine kinase (epidermal growth factor)
      crosstalk in opioid-induced hyperalgesic priming (type II).
AB  - Repeated stimulation of mu-opioid receptors (MORs), by an MOR-selective agonist
      DAMGO induces type II priming, a form of nociceptor neuroplasticity, which has 2
      components: opioid-induced hyperalgesia (OIH) and prolongation of prostaglandin
      E2 (PGE2)-induced hyperalgesia. We report that intrathecal antisense knockdown of
      the MOR in nociceptors, prevented the induction of both components of type II
      priming. Type II priming was also eliminated by SSP-saporin, which destroys the
      peptidergic class of nociceptors. Because the epidermal growth factor receptor
      (EGFR) participates in MOR signaling, we tested its role in type II priming. The
      EGFR inhibitor, tyrphostin AG 1478, prevented the induction of prolonged PGE2
      induced hyperalgesia, but not OIH, when tested out to 30 days after DAMGO.
      However, even when repeatedly injected, an EGFR agonist did not induce
      hyperalgesia or priming. A phosphopeptide, which blocks the interaction of Src,
      focal adhesion kinase (FAK), and EGFR, also prevented DAMGO-induced prolongation
      of PGE2 hyperalgesia, but only partially attenuated the induction of OIH.
      Inhibitors of Src and mitogen-activated protein kinase (MAPK) also only
      attenuated OIH. Inhibitors of matrix metalloproteinase, which cleaves EGF from
      membrane protein, markedly attenuated the expression, but did not prevent the
      induction, of prolongation of PGE2 hyperalgesia. Thus, although the induction of
      prolongation of PGE2-induced hyperalgesia at the peripheral terminal of
      peptidergic nociceptor is dependent on Src, FAK, EGFR, and MAPK signaling, Src,
      FAK, and MAPK signaling is only partially involved in the induction of OIH.

PMID- 29447134
TI  - Histone deacetylase 5 (HDAC5) regulates neuropathic pain through SRY-related HMG
      box 10 (SOX10)-dependent mechanism in mice.
AB  - A strong link between histone deacetylases (HDACs) and nociceptive
      hypersensitivity has been indicated in different pain models. However, the
      underlying molecular and cellular mechanisms remain elusive. Here, we discovered
      that partial sciatic nerve ligation-induced mechanical allodynia and thermal
      hyperalgesia in mice were associated with increased mRNA and protein expressions
      of HDAC5 (a member of class IIa HDACs) and SRY-related HMG-box 10 (SOX10) in the
      ipsilateral lumbar dorsal horn. Gene knockdown of spinal HDAC5 or SOX10
      attenuated partial sciatic nerve ligation-induced nociceptive hypersensitivity,
      companied with decrease of spinal neuronal sensitization markers, namely
      phosphorylated-Erk, phosphorylated-GluN1 (ser896), and c-Fos. Conversely,
      overexpression of spinal HDAC5 or SOX10 by lentiviruses in naive mice not only
      induced pain-like behaviors but also increased the expression of these spinal
      neuronal sensitization markers. Of note, in contrast to its conventional
      deacetylation effect to silence gene expression, overexpression of HDAC5 not only
      enhanced SOX10 expression but also induced nociceptive hypersensitivity in naive
      mice, which were reversed by SOX10 gene knockdown. Chromatin-immunoprecipitation
      assay further confirmed a novel nonhistone modulation function of HDACs on SOX10
      expression, that is, HDAC5 regulates SOX10 by binding to the promoter region of
      Sox10 gene. In conclusion, this study for the first time demonstrates that HDAC5
      regulates spinal neuronal sensitization in neuropathic pain by upregulating
      modulating SOX10 expression. Thus, interventions that reduce HDAC5/SOX10
      expression may represent promising avenues in the treatment of neuropathic pain.

PMID- 29447135
TI  - Introduction to the PAIN supplement on neuropathic pain.

PMID- 29447136
TI  - Individualized neuropathic pain therapy based on phenotyping: are we there yet?
AB  - Patients with the same neuropathic pain disorder may have completely different
      sensory signs and symptoms yet receive the same medicinal treatment. New concepts
      suggest that patient stratification according to their pain mechanisms, reflected
      in their sensory phenotype, could be promising to implement an individualized
      therapy in neuropathic pain. Retrospective classification of patients according
      to their sensory phenotype showed predictive validity and reliability for
      treatment response in certain subgroups of patients. Recent prospective studies
      using stratification based on sensory phenotypes confirm this concept. In this
      article, we review the recent accomplishments towards an individualized
      pharmacological treatment of neuropathic pain.

PMID- 29447137
TI  - Emerging therapies for neuropathic pain: new molecules or new indications for old
      treatments?
AB  - Neuropathic pain represents a highly unmet medical need because most of the
      available treatments have a modest efficacy or dose-limiting side effects. Hence,
      novel therapeutic perspectives are warranted. Many compounds acting on new pain
      targets are in preclinical or early clinical development. Only few clinical
      trials have suggested their clinical relevance in neuropathic pain. This concerns
      in particular NaV1.7 antagonists and angiotensin type II inhibitors. Another type
      of emerging drug therapy in neuropathic pain is represented by drugs largely used
      for other indications, such as botulinum toxin A and the antiepileptic
      oxcarbazepine, which have recently found to be effective in peripheral
      neuropathic pain. Emerging nondrug medical therapy with promising results in
      neuropathic pain also encompasses noninvasive brain neurostimulation techniques,
      such as repetitive transcranial magnetic stimulation and transcranial direct
      electrical stimulation. In this article, we review emerging medical treatments
      for neuropathic pain that are clinically available or with promising results from
      clinical trials.

PMID- 29447138
TI  - Inflammation in the pathophysiology of neuropathic pain.
AB  - Peripheral nerve injuries and diseases often lead to pain persisting beyond the
      resolution of damage, indicating an active disease-promoting process, which may
      result in chronic pain. This is regarded as a maladaptive mechanism resulting
      from neuroinflammation that originally serves to promote regeneration and
      healing. Knowledge on these physiological and pathophysiological processes has
      accumulated over the last few decades and has started to yield potential
      therapeutic targets. Key players are macrophages, T-lymphocytes, cytokines, and
      chemokines. In the spinal cord and brain, microglia and astrocytes are involved.
      Recently, data have been emerging on the regulation of these players. MicroRNAs
      and other noncoding RNAs have been discussed as potential master switches that
      may link nerve injury, pain, and inflammation. Clinical disorders most intensely
      studied in the context of neuroinflammation and pain are the complex regional
      pain syndrome, polyneuropathies, postherpetic neuralgia, and the fibromyalgia
      syndrome, in which recently a neuropathic component has been described. Research
      from several groups has shown an important role of both proinflammatory and anti
      inflammatory cytokines in neuropathic and other chronic pain states in humans.
      There is ample evidence of an analgesic action of anti-inflammatory cytokines in
      animal models. The interplay of anti-inflammatory cytokines and the nociceptive
      system provides possibilities and challenges concerning treatment strategies
      based on this concept.

PMID- 29447139
TI  - Global burden of neuropathic pain.
AB  - Global burden of disease studies measure the impact of disability and premature
      death resulting from specific diseases and injuries. Recently, these studies have
      highlighted the leading contribution of regional pain conditions (low back pain
      and neck pain in particular) to the global burden of disability. However, to
      date, there has not been a systematic approach to measuring the global burden of
      disease attributable to neuropathic pain (NP) conditions. This article gives a
      brief overview of the concept of burden of disease, the underlying drivers, and
      dynamics of disease burden at a population level and proposes an agenda in
      relation to NP for developing the conceptual and empirical evidence base
      necessary for estimating the global burden of NP.

PMID- 29447140
TI  - Resveratrol Improves Endothelial Progenitor Cell Function through miR-138 by
      Targeting Focal Adhesion Kinase (FAK) and Promotes Thrombus Resolution In Vivo.
AB  - BACKGROUND Endothelial progenitor cells (EPCs) were found to be a potential
      therapeutic choice for low extremity deep vein thrombosis. The aim of our
      research was to investigate the effect of resveratrol (RSV) on EPCs that may
      promote thrombus resolution and its potential pathway. MATERIAL AND METHODS EPCs
      were pretreated with RSV and migration; angiogenesis were evaluated ex vivo.
      Expression of miR-138 and focal adhesion kinase (FAK) was also tested. A murine
      model of venous thrombosis was developed as an in vivo model. The effects of RSV
      treatment on mice with inferior venous thrombosis were evaluated. RESULTS We
      found that RSV increased EPCs migration and tube formation ex vivo. RSV
      significantly inhibited miR-138 expression. Moreover, we demonstrated that FAK
      was a target of miR-138 and revealed that FAK knockdown downregulated migration
      and angiogenesis of RSV-treated EPCs. In addition, RSV-induced EPCs promoted
      thrombus resolution in a murine model of venous thrombosis. CONCLUSIONS We found
      the first evidence that intravenous injection of RSV-treated EPCs enhanced
      thrombus resolution in vivo. RSV exerted its role by reducing miR-138 expression
      and therefore upregulated FAK.

PMID- 29447141
TI  - Interim Estimates of 2017-18 Seasonal Influenza Vaccine Effectiveness - United
      States, February 2018.
AB  - In the United States, annual vaccination against seasonal influenza is
      recommended for all persons aged >=6 months (1). During each influenza season
      since 2004-05, CDC has estimated the effectiveness of seasonal influenza vaccine
      to prevent laboratory-confirmed influenza associated with medically attended
      acute respiratory illness (ARI). This report uses data from 4,562 children and
      adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE
      Network) during November 2, 2017-February 3, 2018. During this period, overall
      adjusted vaccine effectiveness (VE) against influenza A and influenza B virus
      infection associated with medically attended ARI was 36% (95% confidence interval
      [CI] = 27%-44%). Most (69%) influenza infections were caused by A(H3N2) viruses.
      VE was estimated to be 25% (CI = 13% to 36%) against illness caused by influenza
      A(H3N2) virus, 67% (CI = 54%-76%) against A(H1N1)pdm09 viruses, and 42% (CI = 25%
      56%) against influenza B viruses. These early VE estimates underscore the need
      for ongoing influenza prevention and treatment measures. CDC continues to
      recommend influenza vaccination because the vaccine can still prevent some
      infections with currently circulating influenza viruses, which are expected to
      continue circulating for several weeks. Even with current vaccine effectiveness
      estimates, vaccination will still prevent influenza illness, including thousands
      of hospitalizations and deaths. Persons aged >=6 months who have not yet been
      vaccinated this season should be vaccinated.

PMID- 29447142
TI  - Prevalence of Obesity Among Youths by Household Income and Education Level of
      Head of Household - United States 2011-2014.
AB  - Obesity prevalence varies by income and education level, although patterns might
      differ among adults and youths (1-3). Previous analyses of national data showed
      that the prevalence of childhood obesity by income and education of household
      head varied across race/Hispanic origin groups (4). CDC analyzed 2011-2014 data
      from the National Health and Nutrition Examination Survey (NHANES) to obtain
      estimates of childhood obesity prevalence by household income (<=130%, >130% to
      <=350%, and >350% of the federal poverty level [FPL]) and head of household
      education level (high school graduate or less, some college, and college
      graduate). During 2011-2014 the prevalence of obesity among U.S. youths (persons
      aged 2-19 years) was 17.0%, and was lower in the highest income group (10.9%)
      than in the other groups (19.9% and 18.9%) and also lower in the highest
      education group (9.6%) than in the other groups (18.3% and 21.6%). Continued
      progress is needed to reduce disparities, a goal of Healthy People 2020. The
      overall Healthy People 2020 target for childhood obesity prevalence is <14.5%
      (5).

PMID- 29447143
TI  - Notes from the Field: Underreporting of Maternal Hepatitis C Virus Infection
      Status and the Need for Infant Testing - Oregon, 2015.

PMID- 29447144
TI  - QuickStats: Age-Adjusted* Trends in the Prevalence of Herpes Simplex Virus Type 1
      (HSV-1) and Herpes Simplex Virus Type 2 (HSV-2) Among Adolescents and Adults Aged
      14-49 Years - United States, 1999-2000 Through 2015-2016.
AB  - During 2015-2016, the age-adjusted prevalence of HSV-1 was 48.1% among
      adolescents and adults aged 14-49 years (50.9% for females and 45.2% for males).
      Prevalence was higher for females than males in most 2-year periods from 1999
      2000 to 2015-2016. Also during 2015-2016, the age-adjusted prevalence of HSV-2
      for those aged 14-49 years was 12.1% (15.9% among females compared to 8.2% among
      males) and was higher for females than males for all 2-year periods. Prevalence
      significantly declined from 1999-2000 through 2015-2016 for HSV-1 and HSV-2 among
      both males and females.

PMID- 29447145
TI  - Update: Influenza Activity - United States, October 1, 2017-February 3, 2018.
AB  - Influenza activity in the United States began to increase in early November 2017
      and rose sharply from December through February 3, 2018; elevated influenza
      activity is expected to continue for several more weeks. Influenza A viruses have
      been most commonly identified, with influenza A(H3N2) viruses predominating, but
      influenza A(H1N1)pdm09 and influenza B viruses were also reported. This report
      summarizes U.S. influenza activity* during October 1, 2017-February 3, 2018,? and
      updates the previous summary (1).

PMID- 29447146
TI  - Health-Risk Behaviors and Chronic Conditions Among Adults with Inflammatory Bowel
      Disease - United States, 2015 and 2016.
AB  - Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative
      colitis, involves chronic inflammation of the gastrointestinal tract. In 2015, an
      estimated 3.1 million adults in the United States had ever received a diagnosis
      of IBD (1). Nationally representative samples of adults with IBD have been
      unavailable or too small to assess relationships between IBD and other chronic
      conditions and health-risk behaviors (2). To assess the prevalence of health-risk
      behaviors and chronic conditions among adults with and without IBD, CDC
      aggregated survey data from the 2015 and 2016 National Health Interview Survey
      (NHIS). An estimated 3.1 million (unadjusted lifetime prevalence = 1.3%) U.S.
      adults had ever received a diagnosis of IBD. Adults with IBD had a significantly
      lower prevalence of having never smoked cigarettes than did adults without the
      disease (55.9% versus 63.5%). Adults with IBD had significantly higher
      prevalences than did those without the disease in the following categories:
      having smoked and quit (26.0% versus 21.0%; having met neither aerobic nor muscle
      strengthening activity guidelines (50.4% versus 45.2%); reporting <7 hours of
      sleep, on average, during a 24-hour period (38.2% versus 32.2%); and having
      serious psychological distress (7.4% versus 3.4%). In addition, nearly all of the
      chronic conditions evaluated were more common among adults with IBD than among
      adults without IBD. Understanding the health-risk behaviors and prevalence of
      certain chronic conditions among adults with IBD could inform clinical practice
      and lead to better disease management.

PMID- 29447148
TI  - Reasons for Electronic Cigarette Use Among Middle and High School Students -
      National Youth Tobacco Survey, United States, 2016.
AB  - Electronic cigarettes (e-cigarettes) were the most commonly used tobacco product
      among U.S. middle school and high school students in 2016 (1). CDC and the Food
      and Drug Administration (FDA) analyzed data from the 2016 National Youth Tobacco
      Survey (NYTS) to assess self-reported reasons for e-cigarette use among U.S.
      middle school (grades 6-8) and high school (grades 9-12) student e-cigarette
      users. Among students who reported ever using e-cigarettes in 2016, the most
      commonly selected reasons for use were 1) use by "friend or family member"
      (39.0%); 2) availability of "flavors such as mint, candy, fruit, or chocolate"
      (31.0%); and 3) the belief that "they are less harmful than other forms of
      tobacco such as cigarettes" (17.1%). The least commonly selected reasons were 1)
      "they are easier to get than other tobacco products, such as cigarettes" (4.8%);
      2) "they cost less than other tobacco products such as cigarettes" (3.2%); and 3)
      "famous people on TV or in movies use them" (1.5%). Availability of flavors as a
      reason for use was more commonly selected by high school users (32.3%) than by
      middle school users (26.8%). Efforts to prevent middle school and high school
      students from initiating the use of any tobacco product, including e-cigarettes,
      are important to reduce tobacco product use among U.S. youths (2).

PMID- 29447147
TI  - Assisted Reproductive Technology Surveillance - United States, 2015.
AB  - PROBLEM/CONDITION: Since the first U.S. infant conceived with assisted
      reproductive technology (ART) was born in 1981, both the use of ART and the
      number of fertility clinics providing ART services have increased steadily in the
      United States. ART includes fertility treatments in which eggs or embryos are
      handled in the laboratory (i.e., in vitro fertilization [IVF] and related
      procedures). Although the majority of infants conceived through ART are
      singletons, women who undergo ART procedures are more likely than women who
      conceive naturally to deliver multiple-birth infants. Multiple births pose
      substantial risks for both mothers and infants, including obstetric
      complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g)
      infants. This report provides state-specific information for the United States
      (including the District of Columbia and Puerto Rico) on ART procedures performed
      in 2015 and compares birth outcomes that occurred in 2015 (resulting from ART
      procedures performed in 2014 and 2015) with outcomes for all infants born in the
      United States in 2015. PERIOD COVERED: 2015. DESCRIPTION OF SYSTEM: In 1995, CDC
      began collecting data on ART procedures performed in fertility clinics in the
      United States as mandated by the Fertility Clinic Success Rate and Certification
      Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). Data are collected
      through the National ART Surveillance System, a web-based data collection system
      developed by CDC. This report includes data from 52 reporting areas (the 50
      states, the District of Columbia, and Puerto Rico). RESULTS: In 2015, a total of
      182,111 ART procedures (range: 135 in Alaska to 23,198 in California) with the
      intent to transfer at least one embryo were performed in 464 U.S. fertility
      clinics and reported to CDC. These procedures resulted in 59,334 live-birth
      deliveries (range: 55 in Wyoming to 7,802 in California) and 71,152 infants born
      (range: 68 in Wyoming to 9,176 in California). Nationally, the number of ART
      procedures performed per 1 million women of reproductive age (15-44 years), a
      proxy measure of the ART utilization rate, was 2,832. ART use exceeded the
      national rate in 13 reporting areas (California, Connecticut, Delaware, the
      District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire,
      New Jersey, New York, Rhode Island, and Virginia). Nationally, among ART transfer
      procedures in patients using fresh embryos from their own eggs, the average
      number of embryos transferred increased with increasing age of the woman (1.6
      among women aged <35 years, 1.8 among women aged 35-37 years, and 2.3 among women
      aged >37 years). Among women aged <35 years, the national elective single-embryo
      transfer (eSET) rate was 34.7% (range: 11.3% in Puerto Rico to 88.1% in
      Delaware). In 2015, ART contributed to 1.7% of all infants born in the United
      States (range: 0.3% in Puerto Rico to 4.5% in Massachusetts). ART also
      contributed to 17.0% of all multiple-birth infants, 16.8% of all twin infants,
      and 22.2% of all triplets and higher-order infants. The percentage of multiple
      birth infants was higher among infants conceived with ART (35.3%) than among all
      infants born in the total birth population (3.4%). Approximately 34.0% of ART
      conceived infants were twins and 1.0% were triplets and higher-order infants.
      Nationally, infants conceived with ART contributed to 5.1% of all low birthweight
      infants. Among ART-conceived infants, 25.5% had low birthweight, compared with
      8.1% among all infants. ART-conceived infants contributed to 5.3% of all preterm
      (gestational age <37 weeks) infants. The percentage of preterm births was higher
      among infants conceived with ART (31.2%) than among all infants born in the total
      birth population (9.7%). Among singletons, the percentage of ART-conceived
      infants who had low birthweight was 8.7% compared with 6.4% among all infants
      born. The percentage of ART-conceived infants who were born preterm was 13.4%
      among singletons compared with 7.9% among all infants. INTERPRETATION: Multiple
      births from ART contributed to a substantial proportion of all twins, triplets,
      and higher-order infants born in the United States. For women aged <35 years, who
      are typically considered good candidates for eSET, the national average of 1.6
      embryos was transferred per ART procedure. Of the four states (Illinois,
      Massachusetts, New Jersey, and Rhode Island) with comprehensive mandated health
      insurance coverage for ART procedures (i.e., coverage for at least four cycles of
      IVF), three (Illinois, Massachusetts, and New Jersey) had rates of ART use
      exceeding 1.5 times the national rate. This type of mandated insurance coverage
      has been associated with greater use of ART and likely accounts for some of the
      difference in per capita ART use observed among states. PUBLIC HEALTH ACTION:
      Twins account for the majority of ART-conceived multiple births. Reducing the
      number of embryos transferred and increasing use of eSET when clinically
      appropriate could help reduce multiple births and related adverse health
      consequences for both mothers and infants. State-based surveillance of ART might
      be useful for monitoring and evaluating maternal and infant health outcomes of
      ART in states with high ART use.

PMID- 29447149
TI  - Optimizing homeostatic cell renewal in hierarchical tissues.
AB  - In order to maintain homeostasis, mature cells removed from the top compartment
      of hierarchical tissues have to be replenished by means of differentiation and
      self-renewal events happening in the more primitive compartments. As each cell
      division is associated with a risk of mutation, cell division patterns have to be
      optimized, in order to minimize or delay the risk of malignancy generation. Here
      we study this optimization problem, focusing on the role of division tree length,
      that is, the number of layers of cells activated in response to the loss of
      terminally differentiated cells, which is related to the balance between
      differentiation and self-renewal events in the compartments. Using both
      analytical methods and stochastic simulations in a metapopulation-style model, we
      find that shorter division trees are advantageous if the objective is to minimize
      the total number of one-hit mutants in the cell population. Longer division trees
      on the other hand minimize the accumulation of two-hit mutants, which is a more
      likely evolutionary goal given the key role played by tumor suppressor genes in
      cancer initiation. While division tree length is the most important property
      determining mutant accumulation, we also find that increasing the size of
      primitive compartments helps to delay two-hit mutant generation.

PMID- 29447150
TI  - Life cycle synchronization is a viral drug resistance mechanism.
AB  - Viral infections are one of the major causes of death worldwide, with HIV
      infection alone resulting in over 1.2 million casualties per year. Antiviral
      drugs are now being administered for a variety of viral infections, including
      HIV, hepatitis B and C, and influenza. These therapies target a specific phase of
      the virus's life cycle, yet their ultimate success depends on a variety of
      factors, such as adherence to a prescribed regimen and the emergence of viral
      drug resistance. The epidemiology and evolution of drug resistance have been
      extensively characterized, and it is generally assumed that drug resistance
      arises from mutations that alter the virus's susceptibility to the direct action
      of the drug. In this paper, we consider the possibility that a virus population
      can evolve towards synchronizing its life cycle with the pattern of drug therapy.
      The periodicity of the drug treatment could then allow for a virus strain whose
      life cycle length is a multiple of the dosing interval to replicate only when the
      concentration of the drug is lowest. This process, referred to as "drug tolerance
      by synchronization", could allow the virus population to maximize its overall
      fitness without having to alter drug binding or complete its life cycle in the
      drug's presence. We use mathematical models and stochastic simulations to show
      that life cycle synchronization can indeed be a mechanism of viral drug
      tolerance. We show that this effect is more likely to occur when the variability
      in both viral life cycle and drug dose timing are low. More generally, we find
      that in the presence of periodic drug levels, time-averaged calculations of viral
      fitness do not accurately predict drug levels needed to eradicate infection, even
      if there is no synchronization. We derive an analytical expression for viral
      fitness that is sufficient to explain the drug-pattern-dependent survival of
      strains with any life cycle length. We discuss the implications of these findings
      for clinically relevant antiviral strategies.

PMID- 29447151
TI  - Quick tips for creating effective and impactful biological pathways using the
      Systems Biology Graphical Notation.

PMID- 29447153
TI  - A model of risk and mental state shifts during social interaction.
AB  - Cooperation and competition between human players in repeated microeconomic games
      offer a window onto social phenomena such as the establishment, breakdown and
      repair of trust. However, although a suitable starting point for the quantitative
      analysis of such games exists, namely the Interactive Partially Observable Markov
      Decision Process (I-POMDP), computational considerations and structural
      limitations have limited its application, and left unmodelled critical features
      of behavior in a canonical trust task. Here, we provide the first analysis of two
      central phenomena: a form of social risk-aversion exhibited by the player who is
      in control of the interaction in the game; and irritation or anger, potentially
      exhibited by both players. Irritation arises when partners apparently defect, and
      it potentially causes a precipitate breakdown in cooperation. Failing to model
      one's partner's propensity for it leads to substantial economic inefficiency. We
      illustrate these behaviours using evidence drawn from the play of large cohorts
      of healthy volunteers and patients. We show that for both cohorts, a particular
      subtype of player is largely responsible for the breakdown of trust, a finding
      which sheds new light on borderline personality disorder.

PMID- 29447152
TI  - A multiscale modelling approach to assess the impact of metabolic zonation and
      microperfusion on the hepatic carbohydrate metabolism.
AB  - The capacity of the liver to convert the metabolic input received from the
      incoming portal and arterial blood into the metabolic output of the outgoing
      venous blood has three major determinants: The intra-hepatic blood flow, the
      transport of metabolites between blood vessels (sinusoids) and hepatocytes and
      the metabolic capacity of hepatocytes. These determinants are not constant across
      the organ: Even in the normal organ, but much more pronounced in the fibrotic and
      cirrhotic liver, regional variability of the capillary blood pressure, tissue
      architecture and the expression level of metabolic enzymes (zonation) have been
      reported. Understanding how this variability may affect the regional metabolic
      capacity of the liver is important for the interpretation of functional liver
      tests and planning of pharmacological and surgical interventions. Here we present
      a mathematical model of the sinusoidal tissue unit (STU) that is composed of a
      single sinusoid surrounded by the space of Disse and a monolayer of hepatocytes.
      The total metabolic output of the liver (arterio-venous glucose difference) is
      obtained by integration across the metabolic output of a representative number of
      STUs. Application of the model to the hepatic glucose metabolism provided the
      following insights: (i) At portal glucose concentrations between 6-8 mM, an intra
      sinusoidal glucose cycle may occur which is constituted by glucose producing
      periportal hepatocytes and glucose consuming pericentral hepatocytes, (ii)
      Regional variability of hepatic blood flow is higher than the corresponding
      regional variability of the metabolic output, (iii) a spatially resolved
      metabolic functiogram of the liver is constructed. Variations of tissue
      parameters are equally important as variations of enzyme activities for the
      control of the arterio-venous glucose difference.

PMID- 29447154
TI  - Examining the controllability of sepsis using genetic algorithms on an agent
      based model of systemic inflammation.
AB  - Sepsis, a manifestation of the body's inflammatory response to injury and
      infection, has a mortality rate of between 28%-50% and affects approximately 1
      million patients annually in the United States. Currently, there are no therapies
      targeting the cellular/molecular processes driving sepsis that have demonstrated
      the ability to control this disease process in the clinical setting. We propose
      that this is in great part due to the considerable heterogeneity of the clinical
      trajectories that constitute clinical "sepsis," and that determining how this
      system can be controlled back into a state of health requires the application of
      concepts drawn from the field of dynamical systems. In this work, we consider the
      human immune system to be a random dynamical system, and investigate its
      potential controllability using an agent-based model of the innate immune
      response (the Innate Immune Response ABM or IIRABM) as a surrogate, proxy system.
      Simulation experiments with the IIRABM provide an explanation as to why
      single/limited cytokine perturbations at a single, or small number of, time
      points is unlikely to significantly improve the mortality rate of sepsis. We then
      use genetic algorithms (GA) to explore and characterize multi-targeted control
      strategies for the random dynamical immune system that guide it from a
      persistent, non-recovering inflammatory state (functionally equivalent to the
      clinical states of systemic inflammatory response syndrome (SIRS) or sepsis) to a
      state of health. We train the GA on a single parameter set with multiple
      stochastic replicates, and show that while the calculated results show good
      generalizability, more advanced strategies are needed to achieve the goal of
      adaptive personalized medicine. This work evaluating the extent of interventions
      needed to control a simplified surrogate model of sepsis provides insight into
      the scope of the clinical challenge, and can serve as a guide on the path towards
      true "precision control" of sepsis.

PMID- 29447155
TI  - Prevalence of trachoma in school children in the Marajo Archipelago, Brazilian
      Amazon, and the impact of the introduction of educational and preventive measures
      on the disease over eight years.
AB  - Trachoma is the leading infectious cause of blindness in the world and is
      associated with precarious living conditions in developing countries. The aim of
      the present study was to evaluate the prevalence of trachoma in three
      municipalities of the Marajo Archipelago, located in the state of Para, Brazil.
      In 2008, 2,054 schoolchildren from the public primary school system of the urban
      area of the region and their communicants were clinically examined; in 2016,
      1,502 schoolchildren were examined. The positive cases seen during the clinical
      evaluation were confirmed by direct immunofluorescence (DIF) laboratory tests.
      The presence of antibodies against the genus Chlamydia was evaluated by indirect
      immunofluorescence (IIF), and the serotypes were determined by
      microimmunofluorescence (MIF). In 2008, the prevalence of trachoma among
      schoolchildren was 3.4% (69 cases) and it was more frequent in children between
      six and nine years of age and in females; among the communicants, a prevalence of
      16.5% was observed. In 2016, three cases of trachoma were diagnosed (prevalence
      of 0.2%), found only in the municipality of Soure. The results of the present
      study showed that in 2008, trachoma had a low prevalence (3.4%) among
      schoolchildren in the urban area of Marajo Archipelago; eight years after the
      first evaluation and the introduction of control and prevention measures (SAFE
      strategy), there was a drastic reduction in the number of cases (0.2%),
      demonstrating the need for constant monitoring and effective measures for the
      elimination of trachoma.

PMID- 29447157
TI  - An inconclusive study comparing the effect of concrete and abstract descriptions
      of belief-inconsistent information.
AB  - Linguistic bias is the differential use of linguistic abstraction (as defined by
      the Linguistic Category Model) to describe the same behaviour for members of
      different groups. Essentially, it is the tendency to use concrete language for
      belief-inconsistent behaviours and abstract language for belief-consistent
      behaviours. Having found that linguistic bias is produced without intention or
      awareness in many contexts, researchers argue that linguistic bias reflects,
      reinforces, and transmits pre-existing beliefs, thus playing a role in belief
      maintenance. Based on the Linguistic Category Model, this assumes that concrete
      descriptions reduce the impact of belief-inconsistent behaviours while abstract
      descriptions maximize the impact of belief-consistent behaviours. However, a key
      study by Geschke, Sassenberg, Ruhrmann, and Sommer [2007] found that concrete
      descriptions of belief-inconsistent behaviours actually had a greater impact than
      abstract descriptions, a finding that does not fit easily within the linguistic
      bias paradigm. Abstract descriptions (e.g. the elderly woman is athletic) are, by
      definition, more open to interpretation than concrete descriptions (e.g. the
      elderly woman works out regularly). It is thus possible that abstract
      descriptions are (1) perceived as having less evidentiary strength than concrete
      descriptions, and (2) understood in context (i.e. athletic for an elderly woman).
      In this study, the design of Geschke et al. [2007] was modified to address this
      possibility. We expected that the differences in the impact of concrete and
      abstract descriptions would be reduced or reversed, but instead we found that
      differences were largely absent. This study did not support the findings of
      Geschke et al. [2007] or the linguistic bias paradigm. We encourage further
      attempts to understand the strong effect of concrete descriptions for belief
      inconsistent behaviour.

PMID- 29447156
TI  - West Nile and St. Louis encephalitis viral genetic determinants of avian host
      competence.
AB  - West Nile virus (WNV) and St. Louis encephalitis (SLEV) virus are enzootically
      maintained in North America in cycles involving the same mosquito vectors and
      similar avian hosts. However, these viruses exhibit dissimilar viremia and
      virulence phenotypes in birds: WNV is associated with high magnitude viremias
      that can result in mortality in certain species such as American crows (AMCRs,
      Corvus brachyrhynchos) whereas SLEV infection yields lower viremias that have not
      been associated with avian mortality. Cross-neutralization of these viruses in
      avian sera has been proposed to explain the reduced circulation of SLEV since the
      introduction of WNV in North America; however, in 2015, both viruses were the
      etiologic agents of concurrent human encephalitis outbreaks in Arizona,
      indicating the need to re-evaluate host factors and cross-neutralization
      responses as factors potentially affecting viral co-circulation. Reciprocal
      chimeric WNV and SLEV viruses were constructed by interchanging the pre-membrane
      (prM)-envelope (E) genes, and viruses subsequently generated were utilized herein
      for the inoculation of three different avian species: house sparrows (HOSPs;
      Passer domesticus), house finches (Haemorhous mexicanus) and AMCRs. Cross
      protective immunity between parental and chimeric viruses were also assessed in
      HOSPs. Results indicated that the prM-E genes did not modulate avian replication
      or virulence differences between WNV and SLEV in any of the three avian species.
      However, WNV-prME proteins did dictate cross-protective immunity between these
      antigenically heterologous viruses. Our data provides further evidence of the
      important role that the WNV / SLEV viral non-structural genetic elements play in
      viral replication, avian host competence and virulence.

PMID- 29447158
TI  - Interaction between nitric oxide and renal alpha1-adrenoreceptors mediated
      vasoconstriction in rats with left ventricular hypertrophyin Wistar Kyoto rats.
AB  - Left ventricular hypertrophy (LVH) is associated with decreased responsiveness of
      renal alpha1-adrenoreceptors subtypes to adrenergic agonists. Nitric oxide donors
      are known to have antihypertrophic effects however their impact on responsiveness
      of renal alpha1-adrenoreceptors subtypes is unknown. This study investigated the
      impact of nitric oxide (NO) and its potential interaction with the responsiveness
      of renal alpha1-adrenoreceptors subtypes to adrenergic stimulation in rats with
      left ventricular hypertrophy (LVH). This study also explored the impact of NO
      donor on CSE expression in normal and LVH kidney. LVH was induced using
      isoprenaline and caffeine in drinking water for 2 weeks while NO donor (L
      arginine, 1.25g/Lin drinking water) was given for 5 weeks. Intrarenal
      noradrenaline, phenylephrine and methoxamine responses were determined in the
      absence and presence of selective alpha1-adrenoceptor antagonists, 5-
      methylurapidil (5-MeU), chloroethylclonidine (CeC) and BMY 7378. Renal cortical
      endothelial nitric oxide synthase mRNA was upregulated 7 fold while that of
      cystathione gamma lyase was unaltered in the NO treated LVH rats (LVH-NO) group
      compared to LVH group. The responsiveness of renal alpha1A, alpha1B and alpha1D
      adrenoceptors in the low dose and high dose phases of 5-MeU, CEC and BMY7378 to
      adrenergic agonists was increased along with cGMP in the kidney of LVH-NO group.
      These findings suggest that exogenous NO precursor up-regulated the renal
      eNOS/NO/cGMP pathway in LVH rats and resulted in augmented alpha1A, alpha1B and
      alpha1D adrenoreceptors responsiveness to the adrenergic agonists. There is a
      positive interaction between H2S and NO production in normal animals but this
      interaction appears absent in LVH animals.

PMID- 29447159
TI  - A comprehensive and quantitative comparison of text-mining in 15 million full
      text articles versus their corresponding abstracts.
AB  - Across academia and industry, text mining has become a popular strategy for
      keeping up with the rapid growth of the scientific literature. Text mining of the
      scientific literature has mostly been carried out on collections of abstracts,
      due to their availability. Here we present an analysis of 15 million English
      scientific full-text articles published during the period 1823-2016. We describe
      the development in article length and publication sub-topics during these nearly
      250 years. We showcase the potential of text mining by extracting published
      protein-protein, disease-gene, and protein subcellular associations using a named
      entity recognition system, and quantitatively report on their accuracy using gold
      standard benchmark data sets. We subsequently compare the findings to
      corresponding results obtained on 16.5 million abstracts included in MEDLINE and
      show that text mining of full-text articles consistently outperforms using
      abstracts only.

PMID- 29447160
TI  - Modeling the interactions of sense and antisense Period transcripts in the
      mammalian circadian clock network.
AB  - In recent years, it has become increasingly apparent that antisense transcription
      plays an important role in the regulation of gene expression. The circadian clock
      is no exception: an antisense transcript of the mammalian core-clock gene PERIOD2
      (PER2), which we shall refer to as Per2AS RNA, oscillates with a circadian period
      and a nearly 12 h phase shift from the peak expression of Per2 mRNA. In this
      paper, we ask whether Per2AS plays a regulatory role in the mammalian circadian
      clock by studying in silico the potential effects of interactions between Per2
      and Per2AS RNAs on circadian rhythms. Based on the antiphasic expression pattern,
      we consider two hypotheses about how Per2 and Per2AS mutually interfere with each
      other's expression. In our pre-transcriptional model, the transcription of Per2AS
      RNA from the non-coding strand represses the transcription of Per2 mRNA from the
      coding strand and vice versa. In our post-transcriptional model, Per2 and Per2AS
      transcripts form a double-stranded RNA duplex, which is rapidly degraded. To
      study these two possible mechanisms, we have added terms describing our
      alternative hypotheses to a published mathematical model of the molecular
      regulatory network of the mammalian circadian clock. Our pre-transcriptional
      model predicts that transcriptional interference between Per2 and Per2AS can
      generate alternative modes of circadian oscillations, which we characterize in
      terms of the amplitude and phase of oscillation of core clock genes. In our post
      transcriptional model, Per2/Per2AS duplex formation dampens the circadian rhythm.
      In a model that combines pre- and post-transcriptional controls, the period,
      amplitude and phase of circadian proteins exhibit non-monotonic dependencies on
      the rate of expression of Per2AS. All three models provide potential explanations
      of the observed antiphasic, circadian oscillations of Per2 and Per2AS RNAs. They
      make discordant predictions that can be tested experimentally in order to
      distinguish among these alternative hypotheses.

PMID- 29447161
TI  - Mycobacterium tuberculosis complex genotypes circulating in Nigeria based on
      spoligotyping obtained from Ziehl-Neelsen stained slides extracted DNA.
AB  - METHODS: All State TB control programmes in Nigeria were requested to submit 25
      50 smear-positive Ziehl-Neelsen (ZN) stained slides for screening during 2013
      2014. DNA was extracted from 929 slides for spoligotyping and drug-resistance
      analysis using microbead-based flow-cytometry suspension arrays. RESULTS:
      Spoligotyping results were obtained for 549 (59.1%) of 929 samples. Lineage 4
      Cameroon sublineage (L4.6.2) represented half of the patterns, Mycobacterium
      africanum (L5 and L6) represented one fifth of the patterns, and all other
      lineages, including other L4 sublineages, represented one third of the patterns.
      Sublineage L4.6.2 was mostly identified in the north of the country whereas L5
      was mostly observed in the south and L6 was scattered. The spatial distribution
      of genotypes had genetic geographic gradients. We did not obtain results enabling
      the detection of drug-resistance mutations. CONCLUSION/SIGNIFICANCE: We present
      the first national snapshot of the M. tuberculosis spoligotypes circulating in
      Nigeria based on ZN slides. Spoligotyping data can be obtained in a rapid and
      high-throughput manner with DNA extracted from ZN-stained slides, which may
      potentially improve our understanding of the genetic epidemiology of TB.

PMID- 29447162
TI  - Early experiences mediate distinct adult gene expression and reproductive
      programs in Caenorhabditis elegans.
AB  - Environmental stress during early development in animals can have profound
      effects on adult phenotypes via programmed changes in gene expression. Using the
      nematode C. elegans, we demonstrated previously that adults retain a cellular
      memory of their developmental experience that is manifested by differences in
      gene expression and life history traits; however, the sophistication of this
      system in response to different environmental stresses, and how it dictates
      phenotypic plasticity in adults that contribute to increased fitness in response
      to distinct environmental challenges, was unknown. Using transcriptional
      profiling, we show here that C. elegans adults indeed retain distinct cellular
      memories of different environmental conditions. We identified approximately 500
      genes in adults that entered dauer due to starvation that exhibit significant
      opposite ("seesaw") transcriptional phenotypes compared to adults that entered
      dauer due to crowding, and are distinct from animals that bypassed dauer.
      Moreover, we show that two-thirds of the genes in the genome experience a 2-fold
      or greater seesaw trend in gene expression, and based upon the direction of
      change, are enriched in large, tightly linked regions on different chromosomes.
      Importantly, these transcriptional programs correspond to significant changes in
      brood size depending on the experienced stress. In addition, we demonstrate that
      while the observed seesaw gene expression changes occur in both somatic and
      germline tissue, only starvation-induced changes require a functional GLP-4
      protein necessary for germline development, and both programs require the
      Argonaute CSR-1. Thus, our results suggest that signaling between the soma and
      the germ line can generate phenotypic plasticity as a result of early
      environmental experience, and likely contribute to increased fitness in adverse
      conditions and the evolution of the C. elegans genome.

PMID- 29447164
TI  - Modern Sunni-Shia conflicts and their neglected tropical diseases.

PMID- 29447163
TI  - Paternal lineage early onset hereditary ovarian cancers: A Familial Ovarian
      Cancer Registry study.
AB  - Given prior evidence that an affected woman conveys a higher risk of ovarian
      cancer to her sister than to her mother, we hypothesized that there exists an X
      linked variant evidenced by transmission to a woman from her paternal grandmother
      via her father. We ascertained 3,499 grandmother/granddaughter pairs from the
      Familial Ovarian Cancer Registry at the Roswell Park Cancer Institute observing
      892 informative pairs with 157 affected granddaughters. We performed germline X
      chromosome exome sequencing on 186 women with ovarian cancer from the registry.
      The rate of cancers was 28.4% in paternal grandmother/granddaughter pairs and
      13.9% in maternal pairs consistent with an X-linked dominant model (Chi-square
      test X2 = 0.02, p = 0.89) and inconsistent with an autosomal dominant model (X2 =
      20.4, p<0.001). Paternal grandmother cases had an earlier age-of-onset versus
      maternal cases (hazard ratio HR = 1.59, 95%CI: 1.12-2.25) independent of BRCA1/2
      status. Reinforcing the X-linked hypothesis, we observed an association between
      prostate cancer in men and ovarian cancer in his mother and daughters (odds
      ratio, OR = 2.34, p = 0.034). Unaffected mothers with affected daughters produced
      significantly more daughters than sons (ratio = 1.96, p<0.005). We performed
      exome sequencing in reported BRCA negative cases from the registry. Considering
      age-of-onset, one missense variant (rs176026 in MAGEC3) reached chromosome-wide
      significance (Hazard ratio HR = 2.85, 95%CI: 1.75-4.65) advancing the age of
      onset by 6.7 years. In addition to the well-known contribution of BRCA, we
      demonstrate that a genetic locus on the X-chromosome contributes to ovarian
      cancer risk. An X-linked pattern of inheritance has implications for genetic risk
      stratification. Women with an affected paternal grandmother and sisters of
      affected women are at increased risk for ovarian cancer. Further work is required
      to validate this variant and to characterize carrier families.

PMID- 29447165
TI  - Comparison of three data mining models for prediction of advanced schistosomiasis
      prognosis in the Hubei province.
AB  - BACKGROUND: In order to better assist medical professionals, this study aimed to
      develop and compare the performance of three models-a multivariate logistic
      regression (LR) model, an artificial neural network (ANN) model, and a decision
      tree (DT) model-to predict the prognosis of patients with advanced
      schistosomiasis residing in the Hubei province. METHODOLOGY/PRINCIPAL FINDINGS:
      Schistosomiasis surveillance data were collected from a previous study based on a
      Hubei population sample including 4136 advanced schistosomiasis cases. The
      predictive models use LR, ANN, and DT methods. From each of the three groups, 70%
      of the cases (2896 cases) were used as training data for the predictive models.
      The remaining 30% of the cases (1240 cases) were used as validation groups for
      performance comparisons between the three models. Prediction performance was
      evaluated using area under the receiver operating characteristic curve (AUC),
      sensitivity, specificity, and accuracy. Univariate analysis indicated that 16
      risk factors were significantly associated with a patient's outcome of prognosis.
      In the training group, the mean AUC was 0.8276 for LR, 0.9267 for ANN, and 0.8229
      for DT. In the validation group, the mean AUC was 0.8349 for LR, 0.8318 for ANN,
      and 0.8148 for DT. The three models yielded similar results in terms of accuracy,
      sensitivity, and specificity. CONCLUSIONS/SIGNIFICANCE: Predictive models for
      advanced schistosomiasis prognosis, respectively using LR, ANN and DT models were
      proved to be effective approaches based on our dataset. The ANN model
      outperformed the LR and DT models in terms of AUC.

PMID- 29447166
TI  - A molecular basis behind heterophylly in an amphibious plant, Ranunculus
      trichophyllus.
AB  - Ranunculus trichophyllus is an amphibious plant that produces thin and
      cylindrical leaves if grown under water but thick and broad leaves if grown on
      land. We found that such heterophylly is widely controlled by two plant hormones,
      abscisic acid (ABA) and ethylene, which control terrestrial and aquatic leaf
      development respectively. Aquatic leaves produced higher levels of ethylene but
      lower levels of ABA than terrestrial leaves. In aquatic leaves, their distinct
      traits with narrow shape, lack of stomata, and reduced vessel development were
      caused by EIN3-mediated overactivation of abaxial genes, RtKANADIs, and
      accompanying with reductions of STOMAGEN and VASCULAR-RELATED NAC-DOMAIN7 (VDN7).
      In contrast, in terrestrial leaves, ABI3-mediated activation of the adaxial
      genes, RtHD-ZIPIIIs, and STOMAGEN and VDN7 established leaf polarity, and stomata
      and vessel developments. Heterophylly of R.trichophyllus could be also induced by
      external cues such as cold and hypoxia, which is accompanied with the changes in
      the expression of leaf polarity genes similar to aquatic response. A closely
      related land plant R. sceleratus did not show such heterophyllic responses,
      suggesting that the changes in the ABA/ethylene signaling and leaf polarity are
      one of key evolutionary steps for aquatic adaptation.

PMID- 29447167
TI  - Activating attachments enhances heart rate variability.
AB  - Although activating mental representations of attachment figures is beneficial
      for psychological health, there is a paucity of knowledge of the underlying
      mechanisms. We investigated how priming attachment figures may modulate
      parasympathetic stress response. Participants (N = 62) with varying degrees of
      attachment security underwent a cold pressor test, and then imagined an
      attachment or non-attachment figure. Heart rate variability was assessed
      throughout the study. Participants with low avoidant attachment levels displayed
      less negative affect and greater heart rate variability following the attachment
      prime than those who imagined the non-attachment prime. This beneficial effect of
      attachment priming was not observed in participants with high avoidant attachment
      levels. These findings highlight that activating attachment representations can
      enhance the parasympathetic stress response in people with secure attachment
      styles, and provides one explanation for the psychological benefits of attachment
      proximity.

PMID- 29447168
TI  - Quantitative proteome profile of water deficit stress responses in eastern
      cottonwood (Populus deltoides) leaves.
AB  - Drought stress is a recurring feature of world climate and the single most
      important factor influencing agricultural yield worldwide. Plants display highly
      variable, species-specific responses to drought and these responses are
      multifaceted, requiring physiological and morphological changes influenced by
      genetic and molecular mechanisms. Moreover, the reproducibility of water deficit
      studies is very cumbersome, which significantly impedes research on drought
      tolerance, because how a plant responds is highly influenced by the timing,
      duration, and intensity of the water deficit. Despite progress in the
      identification of drought-related mechanisms in many plants, the molecular basis
      of drought resistance remains to be fully understood in trees, particularly in
      poplar species because their wide geographic distribution results in varying
      tolerances to drought. Herein, we aimed to better understand this complex
      phenomenon in eastern cottonwood (Populus deltoides) by performing a detailed
      contrast of the proteome changes between two different water deficit experiments
      to identify functional intersections and divergences in proteome responses. We
      investigated plants subjected to cyclic water deficit and compared these
      responses to plants subjected to prolonged acute water deficit. In total, we
      identified 108,012 peptide sequences across both experiments that provided
      insight into the quantitative state of 22,737 Populus gene models and 8,199
      functional protein groups in response to drought. Together, these datasets
      provide the most comprehensive insight into proteome drought responses in poplar
      to date and a direct proteome comparison between short period dehydration shock
      and cyclic, post-drought re-watering. Overall, this investigation provides novel
      insights into drought avoidance mechanisms that are distinct from progressive
      drought stress. Additionally, we identified proteins that have been associated as
      drought-relevant in previous studies. Importantly, we highlight the RD26
      transcription factor as a gene regulated at both the transcript and protein
      level, regardless of species and drought condition, and, thus, represents a key,
      universal drought marker for Populus species.

PMID- 29447169
TI  - Occurrence of measles in a country with elimination status: Amplifying measles
      infection in hospitalized children due to imported virus.
AB  - The Republic of Korea declared measles elimination in 2006. However, a measles
      outbreak occurred in 2013. This study aimed to identify the epidemiological
      characteristics of the sources of infection and the pattern of measles
      transmission in 2013 in South Korea. We utilized surveillance data,
      epidemiological data, immunization registry data, and genetic information. We
      describe the epidemiological characteristics of all measles case patients (sex,
      age distribution, vaccination status, sources of infection) as well as details of
      the outbreak (the pattern of transmission, duration, mean age of patients, and
      generation time). In 2013, a total of 107 measles cases were notified. Most
      patients were infants (43.0%) and unvaccinated individuals (60.7%). We identified
      4 imported and 103 import-related cases. A total of 105 cases were related to
      four outbreaks that occurred in Gyeongnam, northern Gyeonggi, southern Gyeonggi,
      and Seoul. The predominant circulating genotype was B3 type, which was identified
      in the Gyeongnam, northern Gyeonggi, and southern Gyeonggi outbreaks. The B3 type
      had not been in circulation in South Korea in the previous 3 years; virologic
      evidence suggests that these outbreaks were import-related. Most measles cases in
      South Korea have been associated with imported measles virus. Although Korea has
      maintained a high level of herd immunity, clustering of susceptible people can
      cause such measles outbreaks.

PMID- 29447170
TI  - Imported endemic mycoses in Spain: Evolution of hospitalized cases, clinical
      characteristics and correlation with migratory movements, 1997-2014.
AB  - Endemic mycoses are systemic fungal infections. Histoplasmosis is endemic in all
      temperate areas of the world; coccidioidomycosis and paracoccidioidomycosis are
      only present in the American continent. These pathogens are not present in Spain,
      but in the last years there has been an increase of reported cases due to
      migration and temporary movements. We obtained from the Spanish hospitals records
      clinical and demographic data of all hospitalized cases between 1997 and 2014.
      There were 286 cases of histoplasmosis, 94 of Coccidioidomycosis and 25 of
      paracoccidioidomycosis. Overall, histoplasmosis was strongly related to HIV
      infection, as well as with greater morbidity and mortality. For the other
      mycoses, we did not find any immunosuppressive condition in most of the cases.
      Although we were not able to obtain data about clinical presentation of all the
      cases, the most frequently found was pulmonary involvement. We also found a
      temporal correlation between the Spanish population born in endemic countries and
      the number of hospitalized cases along this period. This study reflects the
      importance of imported diseases in non-endemic countries due to migratory
      movements.

PMID- 29447172
TI  - Knowledge, attitude and associated factors among primary school teachers
      regarding refractive error in school children in Gondar city, Northwest Ethiopia.
AB  - INTRODUCTION: Refractive error is an important cause of correctable visual
      impairment in the worldwide with a global distribution of 1.75% to 20.7% among
      schoolchildren. Teacher's knowledge about refractive error play an important role
      in encouraging students to seek treatment that helps in reducing the burden of
      visual impairment. OBJECTIVE: To determine knowledge, attitude and associated
      factors among primary school teachers regarding refractive error in school
      children in Gondar city. METHODS: Institution based cross-sectional study was
      conducted on 565 primary school teachers in Gondar city using pretested and
      structured self-administered questionnaire. For processing and analysis, SPSS
      version 20 was used and variables which had a P value of <0.05 in the
      multivariable analysis were considered as statistically significant. RESULT: A
      total of 565 study subjects were participated in this study with a mean age of
      42.05 +/- 12.01 years. Of these study participants 55.9% (95% CI: 51.9, 59.8) had
      good knowledge and 57.2% (95% CI: 52.9, 61.4) had favorable attitude towards
      refractive error. History of spectacle use [AOR = 2.13 (95% CI: 1.32, 3.43)],
      history of eye examination [AOR = 1.67 (95% CI: 1.19, 2.34)], training on eye
      health [AOR = 1.94 (95% CI; 1.09, 3.43)] and 11-20 years of experience [AOR =
      2.53 (95% CI: 1.18, 5.43)] were positively associated with knowledge. Whereas
      being male [AOR = 2.03 (95% CI: 1.37, 3.01)], older age [AOR = 3.05 (95% CI:
      1.07, 8.72)], 31-40 years of experience [AOR = 0.23 (95% CI: 0.07, 0.72)],
      private school type [AOR = 1.76 (95% CI: 1.06, 2.93)] and 5th -8th teaching
      category [AOR = 1.54 (95% CI: 1.05, 2.24)] were associated with attitude.
      CONCLUSION: Knowledge and attitude of study subjects were low which needs
      training of teachers about the refractive error.

PMID- 29447171
TI  - Brca2, Pds5 and Wapl differentially control cohesin chromosome association and
      function.
AB  - The cohesin complex topologically encircles chromosomes and mediates sister
      chromatid cohesion to ensure accurate chromosome segregation upon cell division.
      Cohesin also participates in DNA repair and gene transcription. The Nipped-B-Mau2
      protein complex loads cohesin onto chromosomes and the Pds5-Wapl complex removes
      cohesin. Pds5 is also essential for sister chromatid cohesion, indicating that it
      has functions beyond cohesin removal. The Brca2 DNA repair protein interacts with
      Pds5, but the roles of this complex beyond DNA repair are unknown. Here we show
      that Brca2 opposes Pds5 function in sister chromatid cohesion by assaying
      precocious sister chromatid separation in metaphase spreads of cultured cells
      depleted for these proteins. By genome-wide chromatin immunoprecipitation we find
      that Pds5 facilitates SA cohesin subunit association with DNA replication origins
      and that Brca2 inhibits SA binding, mirroring their effects on sister chromatid
      cohesion. Cohesin binding is maximal at replication origins and extends outward
      to occupy active genes and regulatory sequences. Pds5 and Wapl, but not Brca2,
      limit the distance that cohesin extends from origins, thereby determining which
      active genes, enhancers and silencers bind cohesin. Using RNA-seq we find that
      Brca2, Pds5 and Wapl influence the expression of most genes sensitive to Nipped-B
      and cohesin, largely in the same direction. These findings demonstrate that Brca2
      regulates sister chromatid cohesion and gene expression in addition to its
      canonical role in DNA repair and expand the known functions of accessory proteins
      in cohesin's diverse functions.

PMID- 29447173
TI  - Dynamic changes of SETD2, a histone H3K36 methyltransferase, in porcine oocytes,
      IVF and SCNT embryos.
AB  - SETD2 (SET domain containing protein 2) acts as a histone H3 lysine 36 (H3K36)
      specific methyltransferase and may play important roles in active gene
      transcription in human cells. However, its expression and role in porcine oocytes
      and preimplantation embryos are not well understood. Here, we used
      immunofluorescence and laser scanning confocal microscopy to examine SETD2
      expression in porcine fetal fibroblasts, oocytes, and preimplantation embryos
      derived from in vitro fertilization (IVF), parthenogenetic activation (PA), and
      somatic cell nuclear transfer (SCNT). In porcine fetal fibroblasts, SETD2
      expression was detected in interphase cells, but not in M (mitotic)-phase cells.
      The SETD2 signal was observed in non-surrounded nucleolus (NSN)-stage oocytes,
      but not in surrounded nucleolus (SN)-, metaphase I (MI)-, or metaphase II (MII)
      stage oocytes. The SETD2 signal was detectable in sperm, and undetectable
      immediately after fertilization, detectable at the 2-cell stage, and peaked at
      the 4-cell stage of IVF embryos in which porcine embryonic genome is activated.
      Similar to the pattern found in IVF embryos, the SETD2 signal was absent from PA
      embryos at the 1-cell stage, but it was detected at the 2-cell stage and
      thereafter maintained to the blastocyst stage. Interestingly, unlike the IVF and
      PA embryos, the SETD2 signal was detected throughout the development of SCNT
      embryos, including at the 1-cell stage. These data suggest that SETD2 may be
      functional for embryonic gene transcription in porcine preimplantation embryos.
      It is further speculated that the aberrant expression of SETD2 at the 1-cell
      stage of porcine SCNT embryos may be a factor in the low efficiency of cloning in
      pig.

PMID- 29447174
TI  - Long-term cardiovascular risk of hypertensive events in emergency department: A
      population-based 10-year follow-up study.
AB  - BACKGROUND: Hypertension-related visits to the emergency department (ED) are
      increasing every year. Thus, ED could play a significant role in detecting
      hypertension and providing necessary interventions. However, it is not known
      whether a hypertensive event observed in the ED is an independent risk factor for
      future major adverse cardiovascular events (MACE). METHODS: A population-based
      observational study was conducted using a nationally representative cohort that
      contained the claim data of 1 million individuals from 2002 to 2013. We included
      non-critical ED visits without any history of MACE, and compared the new
      occurrences of MACE according to the presence of hypertensive events using
      extended Cox regression model. The disease-modifying effect of a follow-up visit
      was assessed by analyzing the interaction between hypertensive event and follow
      up visit. RESULTS: Among 262,927 first non-critical ED visits during the study
      period (from 2004 to 2013), 6,243 (2.4%) visits were accompanied by a
      hypertensive event. The hypertensive event group had a higher risk of having a
      first MACE at 3 pre-specified intervals: 0-3 years (HR, 4.25; 95% CI, 3.83-4.71;
      P<0.001), 4-6 years (HR, 3.65; 95% CI, 3.14-4.24; P<0.001), and 7-10 years (HR,
      3.20; 95% CI, 2.50-4.11; P<0.001). Follow-up visits showed significant disease
      modifying effect at 2 intervals: 0-3 years (HR 0.65, 95% CI, 0.50-0.83) and 4-7
      years (HR 0.68, 95% CI, 0.48-0.95). CONCLUSIONS: A hypertensive event in the ED
      is an independent risk factor for MACE, and follow-up visits after the event can
      significantly modify the risk.

PMID- 29447175
TI  - Modelling human hard palate shape with Bezier curves.
AB  - People vary at most levels, from the molecular to the cognitive, and the shape of
      the hard palate (the bony roof of the mouth) is no exception. The patterns of
      variation in the hard palate are important for the forensic sciences and
      (palaeo)anthropology, and might also play a role in speech production, both in
      pathological cases and normal variation. Here we describe a method based on
      Bezier curves, whose main aim is to generate possible shapes of the hard palate
      in humans for use in computer simulations of speech production and language
      evolution. Moreover, our method can also capture existing patterns of variation
      using few and easy-to-interpret parameters, and fits actual data obtained from
      MRI traces very well with as little as two or three free parameters. When
      compared to the widely-used Principal Component Analysis (PCA), our method fits
      actual data slightly worse for the same number of degrees of freedom. However, it
      is much better at generating new shapes without requiring a calibration sample,
      its parameters have clearer interpretations, and their ranges are grounded in
      geometrical considerations.

PMID- 29447176
TI  - Cost-effectiveness of prenatal food and micronutrient interventions on under-five
      mortality and stunting: Analysis of data from the MINIMat randomized trial,
      Bangladesh.
AB  - INTRODUCTION: Nutrition interventions may have favourable as well as unfavourable
      effects. The Maternal and Infant Nutrition Interventions in Matlab (MINIMat),
      with early prenatal food and micronutrient supplementation, reduced infant
      mortality and were reported to be very cost-effective. However, the multiple
      micronutrients (MMS) supplement was associated with an increased risk of stunted
      growth in infancy and early childhood. This unfavourable outcome was not included
      in the previous cost-effectiveness analysis. The aim of this study is to evaluate
      whether the MINIMat interventions remain cost-effective in view of both
      favourable (decreased under-five-years mortality) and unfavourable (increased
      stunting) outcomes. METHOD: Pregnant women in rural Bangladesh, where food
      insecurity still is prevalent, were randomized to early (E) or usual (U)
      invitation to be given food supplementation and daily doses of 30 mg, or 60 mg
      iron with 400 MUg of folic acid, or MMS with 15 micronutrients including 30 mg
      iron and 400 MUg of folic acid. E reduced stunting at 4.5 years compared with U,
      MMS increased stunting at 4.5 years compared with Fe60, while the combination
      EMMS reduced infant mortality compared with UFe60. The outcome measure used was
      disability adjusted life years (DALYs), a measure of overall disease burden that
      combines years of life lost due to premature mortality (under five-year
      mortality) and years lived with disability (stunting). Incremental cost
      effectiveness ratios were calculated using cost data from already published
      studies. RESULTS: By incrementing UFe60 (standard practice) to EMMS, one DALY
      could be averted at a cost of US$24. CONCLUSION: When both favourable and
      unfavourable outcomes were included in the analysis, early prenatal food and
      multiple micronutrient interventions remained highly cost effective and seem to
      be meaningful from a public health perspective.

PMID- 29447177
TI  - Physician prescribing of opioid agonist treatments in provincial correctional
      facilities in Ontario, Canada: A survey.
AB  - BACKGROUND: Substance use and substance use disorders are common in people who
      experience detention or incarceration in Canada, and opioid agonist treatment
      (OAT) may reduce the harms associated with substance use disorders. We aimed to
      define current physician practice in provincial correctional facilities in
      Ontario with respect to prescribing OAT and to identify potential barriers and
      facilitators to prescribing OAT. METHODS: We invited all physicians practicing in
      the 26 provincial correctional facilities for adults in Ontario to participate in
      an online survey. RESULTS: Twenty-seven physicians participated, with
      representation from most correctional facilities in Ontario. Of participating
      physicians, 52% reported prescribing methadone and 48% reported prescribing
      buprenorphine/naloxone to patients in provincial correctional facilities.
      Nineteen percent of participants reported initiating methadone treatment and 11%
      reported initiating buprenorphine/naloxone for patients in custody. Participants
      identified multiple barriers to initiating OAT in provincial correctional
      facilities including concerns about medication diversion and safety, concerns
      about initiating treatment in patients who are not currently using opioids, lack
      of linkage with community-based providers and the Ministry of Community Safety
      and Correctional Services policy. Identified facilitators to initiating OAT were
      support from institutional health care staff and administrative staff, adequate
      resources for program delivery and access to linkage with community-based OAT
      providers. CONCLUSIONS: This study identifies opportunities to improve OAT
      programs and to improve access to OAT for persons in provincial correctional
      facilities in Ontario.

PMID- 29447178
TI  - Joint ancestry and association test indicate two distinct pathogenic pathways
      involved in classical dengue fever and dengue shock syndrome.
AB  - Ethnic diversity has been long considered as one of the factors explaining why
      the severe forms of dengue are more prevalent in Southeast Asia than anywhere
      else. Here we take advantage of the admixed profile of Southeast Asians to
      perform coupled association-admixture analyses in Thai cohorts. For dengue shock
      syndrome (DSS), the significant haplotypes are located in genes coding for
      phospholipase C members (PLCB4 added to previously reported PLCE1), related to
      inflammation of blood vessels. For dengue fever (DF), we found evidence of
      significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which
      participate in the xenobiotic metabolism signaling pathway. We conducted
      functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the
      coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly,
      only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top
      linking motif in NS5 abolished the nuclear transfer. These observations support
      the existence of differences between serotypes in their cellular dynamics, which
      may contribute to differential infection outcome risk. The contribution of the
      identified genes to the genetic risk render Southeast and Northeast Asian
      populations more susceptible to both phenotypes, while African populations are
      best protected against DSS and intermediately protected against DF, and Europeans
      the best protected against DF but the most susceptible against DSS.

PMID- 29447179
TI  - Isolation and identification of new bacterial stains producing equol from
      Pueraria lobata extract fermentation.
AB  - Equol is a nonsteroidal estrogen that is produced by intestinal bacterial
      metabolism. Equol and equol-producing bacteria have been extensively investigated
      with soybean-based materials under anaerobic condition. In this study, an under
      appreciated plant material, Pueraria lobata, was used to find new bacterial
      strains that produce equol under aerobic conditions. Three new intestinal
      bacteria, CS1, CS2, and CS3, were isolated, and internal transcribed spacer
      analysis revealed that belonging to genus Pediococcus and Lactobacillus. HPLC
      analysis showed that these strains produced equol or its related intermediates
      when fermenting P. lobata extract. In comparison to fermentation of P. lobata
      extract, soybean germ extract was also fermented. While the isolated strains did
      not produce equol in this extract, they produced other equol-related precursors.
      To test the modularity effect of these fermentation mixtures with the newly
      isolated bacteria, MCF-7 cell proliferation assay was performed, which showed
      that all extracts fermented with those strains has a modularity effect.
      Fermenting P. lobata extract with strain CS1 demonstrated the best modularity
      effect.

PMID- 29447180
TI  - Experimental research on the structural instability mechanism and the effect of
      multi-echelon support of deep roadways in a kilometre-deep well.
AB  - We study the structural instability mechanism and effect of a multi-echelon
      support in very-deep roadways. We conduct a scale model test for analysing the
      structural failure mechanism and the effect of multi-echelon support of roadways
      under high horizontal stress. Mechanical bearing structures are classified
      according to their secondary stress distribution and the strength degradation of
      the surrounding rock after roadway excavation. A new method is proposed by
      partitioning the mechanical bearing structure of the surrounding rock into weak,
      key and main coupling bearing stratums. In the surrounding rock, the main bearing
      stratum is the plastic reshaping and flowing area. The weak bearing stratum is
      the peeling layer or the caving part. And the key bearing stratum is the shearing
      and yielding area. The structural fracture mechanism of roadways is considered in
      analysing the bearing structure instability of the surrounding rock, and multi
      echelon support that considers the structural characteristics of roadway bearings
      is proposed. Results of the experimental study indicate that horizontal pressure
      seriously influences the stability of the surrounding rock, as indicated by
      extension of the weak bearing area and the transfer of the main and key bearing
      zones. The falling roof, rib spalling, and floor heave indicate the decline of
      the bearing capacity of surrounding rock, thereby causing roadway structural
      instability. Multi-echelon support is proposed according to the mechanical
      bearing structure of the surrounding rock without support. The redesigned support
      can reduce the scope of the weak bearing area and limit the transfer of the main
      and key bearing areas. Consequently, kilometre-deep roadway disasters, such as
      wedge roof caving, floor heave, and rib spalling, can be avoided to a certain
      degree, and plastic flow in the surrounding rock is relieved. The adverse effect
      of horizontal stress on the vault, spandrel and arch foot decreases. The
      stability of the soft rock surrounding the roadways is maintained.

PMID- 29447181
TI  - Innate immune responses following Kawasaki disease and toxic shock syndrome.
AB  - The pathogenesis of Kawasaki disease (KD) remains unknown and there is
      accumulating evidence for the importance of the innate immune system in
      initiating and mediating the host inflammatory response. We compared innate
      immune responses in KD and toxic shock syndrome (TSS) participants more than two
      years after their acute illness with control participants to investigate
      differences in their immune phenotype. Toxic shock syndrome shares many clinical
      features with KD; by including both disease groups we endeavoured to explore
      changes in innate immune responses following acute inflammatory illnesses more
      broadly. We measured the in vitro production of interferon (IFN)-gamma, tumour
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-1 receptor
      antagonist (IL-1ra), and IL-10 following whole blood stimulation with toll-like
      receptor and inflammasome ligands in 52 KD, 20 TSS, and 53 control participants
      in a case-control study. Analyses were adjusted for age, sex, and unstimulated
      cytokine concentrations. Compared to controls, KD participants have reduced IL
      1ra production in response to stimulation with double stranded RNA (geometric
      mean ratio (GMR) 0.37, 95% CI 0.15, 0.89, p = 0.03) and increased IL-6 production
      in response to incubation with LyovecTM (GMR 5.48, 95% CI 1.77, 16.98, p =
      0.004). Compared to controls, TSS participants have increased IFN-gamma
      production in response to peptidoglycan (GMR 4.07, 95% CI 1.82, 9.11, p = 0.001),
      increased IL-1beta production to lipopolysaccharide (GMR 1.64, 95% CI 1.13, 2.38,
      p = 0.01) and peptidoglycan (GMR 1.61, 95% CI 1.11, 2.33, p = 0.01), and
      increased IL-6 production to peptidoglycan (GMR 1.45, 95% CI 1.10, 1.92, p =
      0.01). Years following the acute illness, individuals with previous KD or TSS
      exhibit a pro-inflammatory innate immune phenotype suggesting a possible
      underlying immunological susceptibility or innate immune memory.

PMID- 29447182
TI  - The impact of EGFR mutations on the incidence and survival of stages I to III
      NSCLC patients with subsequent brain metastasis.
AB  - Previous studies have demonstrated the association between EGFR mutations and
      distant metastasis. However, the association for subsequent brain metastasis (BM)
      in stages I-III non-small cell lung cancer (NSCLC) patients remains inconclusive.
      We conducted a retrospective analysis to clarify the impact of EGFR mutations on
      the incidence of BM and associated survival in patients with stage I-III NSCLC. A
      total of 491 patients screened for EGFR mutations were retrospectively enrolled.
      Brain MRI or CT was used to detect the BM. Cumulative incidence of subsequent BM
      and overall survival (OS) after diagnosis of BM were estimated by the Kaplan
      Meier method and compared using log-rank test. We performed Cox proportional
      hazard regression for predictors of subsequent BM and determinants of OS after
      BM. The cumulative incidence of BM seemed higher in patients harboring EGFR
      mutations than those without EGFR mutations although it did not reach statistical
      significance (hazard ratio [HR] = 1.75, 95% confidence interval [CI] =
      0.73~1.81). After adjusting possible confounders, including age, smoking, stage,
      and tumor size, EGFR mutation became one of the predictors for subsequent BM (HR
      = 1.89, 95% CI = 1.12~3.17, p = 0.017). Though there was no statistical
      difference in survival after BM between patients with EGFR mutations and wild
      type EGFR (median survival: 17.8 vs. 12.2 months, HR = 0.79, 95% CI = 0.45-1.40),
      patients with EGFR 19 deletion (Del) tended to have a longer survival after BM
      than the non-EGFR 19 Del group (median survival: 29.4 vs. 14.3 months, HR 0.58,
      95% CI = 0.32-1.09, p = 0.089). In conclusion, our data suggested EGFR mutation
      to be one of the predictors for subsequent BM in stage I-III patients. Given the
      small sample size, more studies are warranted to corroborate our results.

PMID- 29447183
TI  - A mass-density model can account for the size-weight illusion.
AB  - When judging the heaviness of two objects with equal mass, people perceive the
      smaller and denser of the two as being heavier. Despite the large number of
      theories, covering bottom-up and top-down approaches, none of them can fully
      account for all aspects of this size-weight illusion and thus for human heaviness
      perception. Here we propose a new maximum-likelihood estimation model which
      describes the illusion as the weighted average of two heaviness estimates with
      correlated noise: One estimate derived from the object's mass, and the other from
      the object's density, with estimates' weights based on their relative
      reliabilities. While information about mass can directly be perceived,
      information about density will in some cases first have to be derived from mass
      and volume. However, according to our model at the crucial perceptual level,
      heaviness judgments will be biased by the objects' density, not by its size. In
      two magnitude estimation experiments, we tested model predictions for the visual
      and the haptic size-weight illusion. Participants lifted objects which varied in
      mass and density. We additionally varied the reliability of the density estimate
      by varying the quality of either visual (Experiment 1) or haptic (Experiment 2)
      volume information. As predicted, with increasing quality of volume information,
      heaviness judgments were increasingly biased towards the object's density:
      Objects of the same density were perceived as more similar and big objects were
      perceived as increasingly lighter than small (denser) objects of the same mass.
      This perceived difference increased with an increasing difference in density. In
      an additional two-alternative forced choice heaviness experiment, we replicated
      that the illusion strength increased with the quality of volume information
      (Experiment 3). Overall, the results highly corroborate our model, which seems
      promising as a starting point for a unifying framework for the size-weight
      illusion and human heaviness perception.

PMID- 29447184
TI  - Greenery in the university environment: Students' preferences and perceived
      restoration likelihood.
AB  - A large body of evidence shows that interaction with greenery can be beneficial
      for human stress reduction, emotional states, and improved cognitive function. It
      can, therefore, be expected that university students might benefit from greenery
      in the university environment. Before investing in real-life interventions in a
      university environment, it is necessary to first explore students' perceptions of
      greenery in the university environment. This study examined (1) preference for
      university indoor and outdoor spaces with and without greenery (2) perceived
      restoration likelihood of university outdoor spaces with and without greenery and
      (3) if preference and perceived restoration likelihood ratings were modified by
      demographic characteristics or connectedness to nature in Dutch university
      students (N = 722). Digital photographic stimuli represented four university
      spaces (lecture hall, classroom, study area, university outdoor space). For each
      of the three indoor spaces there were four or five stimuli conditions: (1) the
      standard design (2) the standard design with a colorful poster (3) the standard
      design with a nature poster (4) the standard design with a green wall (5) the
      standard design with a green wall plus interior plants. The university outdoor
      space included: (1) the standard design (2) the standard design with seating (3)
      the standard design with colorful artifacts (4) the standard design with green
      elements (5) the standard design with extensive greenery. Multi-level analyses
      showed that students gave higher preference ratings to the indoor spaces with a
      nature poster, a green wall, or a green wall plus interior plants than to the
      standard designs and the designs with the colorful posters. Students also rated
      preference and perceived restoration likelihood of the outdoor spaces that
      included greenery higher than those without. Preference and perceived restoration
      likelihood were not modified by demographic characteristics, but students with
      strong connectedness to nature rated preference and perceived restoration
      likelihood overall higher than students with weak connectedness to nature. The
      findings suggest that students would appreciate the integration of greenery in
      the university environment.

PMID- 29447185
TI  - Egg turning behavior and incubation temperature in Forster's terns in relation to
      mercury contamination.
AB  - Egg turning behavior is an important determinant of egg hatchability, but it
      remains relatively understudied. Here, we examined egg turning rates and egg
      temperatures in Forster's terns (Sterna forsteri). We used artificial eggs
      containing a data logger with a 3-D accelerometer, a magnetometer, and a
      temperature thermistor to monitor parental incubation behavior of 131 tern nests.
      Overall, adults turned their eggs an average (+/-SD) of 3.8 +/- 0.8 turns h-1,
      which is nearly two times higher than that of other seabirds. Egg turning rates
      increased with nest initiation date. We also examined egg turning rates and egg
      temperatures in relation to egg mercury contamination. Mercury contamination has
      been shown to be associated with reduced egg hatchability, and we hypothesized
      that mercury may decrease egg hatchability via altered egg turning behavior by
      parents. Despite the high variability in egg turning rates among individuals, the
      rate of egg turning was not related to mercury concentrations in sibling eggs.
      These findings highlight the need for further study concerning the potential
      determinants of egg turning behavior.

PMID- 29447186
TI  - Can an experimental white noise task assess psychosis vulnerability in adult
      healthy controls?
AB  - BACKGROUND: This is an extension of a paper published earlier. We investigated
      the association between the tendency to detect speech illusion in random noise
      and levels of positive schizotypy in a sample of 185 adult healthy controls.
      MATERIALS AND METHODS: Subclinical positive, negative and depressive symptoms
      were assessed with the Community Assessment of Psychic Experiences (CAPE);
      positive and negative schizotypy was assessed with the Structured Interview for
      Schizotypy-Revised (SIS-R). RESULTS: Speech illusions were associated with
      positive schizotypy (OR: 4.139, 95% CI: 1.074-15.938; p = 0.039) but not with
      negative schizotypy (OR: 1.151, 95% CI: 0.183-7.244; p = 0.881). However, the
      association of positive schizotypy with speech illusions was no longer
      significant after adjusting for age, sex and WAIS-III (OR: 2.577, 95% CI: 0.620
      10.700; p = 0.192). Speech illusions were not associated with self-reported CAPE
      measures. CONCLUSIONS: The association between schizotypy and the tendency to
      assign meaning in random noise in healthy controls may be mediated by cognitive
      ability and not constitute an independent trait.

PMID- 29447187
TI  - Comparative study on the mechanical mechanism of confined concrete supporting
      arches in underground engineering.
AB  - In order to solve the supporting problem in underground engineering with high
      stress, square steel confined concrete (SQCC) supporting method is adopted to
      enhance the control on surrounding rocks, and the control effect is remarkable.
      The commonly used cross section shapes of confined concrete arch are square and
      circular. At present, designers have no consensus on which kind is more proper.
      To search for the answer, this paper makes an analysis on the mechanical
      properties of the two shapes of the cross-sections. A full-scale indoor
      comparative test was carried out on the commonly used straight-wall semi-circular
      SQCC arch and circular steel confined concrete arch (CCC arch). This test is
      based on self-developed full-scale test system for confined concrete arch. Our
      research, combining with the numerical analysis, shows: (1) SQCC arch is
      consistent with CCC arch in the deformation and failure mode. The largest damages
      parts are at the legs of both of them. (2) The SQCC arch's bearing capability is
      1286.9 kN, and the CCC arch's ultimate bearing capability is 1072.4kN. Thus, the
      SQCC arch's bearing capability is 1.2 times that of the CCC arch. (3) The arches
      are subjected to combined compression and bending, bending moment is the main
      reason for the arch failure. The section moment of inertia of SQCC arch is 1.26
      times of that of CCC arch, and the former is better than the latter in bending
      performance. The ultimate bearing capacity is positively correlated with the size
      of the moment of inertia. Based on the above research, the engineering
      suggestions are as follows: (1) To improve the bearing capacity of the arch, the
      cross-sectional shape of the chamber should be optimized and the arch bearing
      mode changed accordingly. (2) The key damaged positions, such as the arch leg,
      should be reinforced, optimizing the state of force on the arch. SQCC arches
      should be used for supporting in underground engineering, which is under stronger
      influence of the bending moment and non-uniform load on the supporting arches.
      The research results could provide a theoretical basis for the design of confined
      concrete support in underground engineering.

PMID- 29447188
TI  - Comparing deep learning and concept extraction based methods for patient
      phenotyping from clinical narratives.
AB  - In secondary analysis of electronic health records, a crucial task consists in
      correctly identifying the patient cohort under investigation. In many cases, the
      most valuable and relevant information for an accurate classification of medical
      conditions exist only in clinical narratives. Therefore, it is necessary to use
      natural language processing (NLP) techniques to extract and evaluate these
      narratives. The most commonly used approach to this problem relies on extracting
      a number of clinician-defined medical concepts from text and using machine
      learning techniques to identify whether a particular patient has a certain
      condition. However, recent advances in deep learning and NLP enable models to
      learn a rich representation of (medical) language. Convolutional neural networks
      (CNN) for text classification can augment the existing techniques by leveraging
      the representation of language to learn which phrases in a text are relevant for
      a given medical condition. In this work, we compare concept extraction based
      methods with CNNs and other commonly used models in NLP in ten phenotyping tasks
      using 1,610 discharge summaries from the MIMIC-III database. We show that CNNs
      outperform concept extraction based methods in almost all of the tasks, with an
      improvement in F1-score of up to 26 and up to 7 percentage points in area under
      the ROC curve (AUC). We additionally assess the interpretability of both
      approaches by presenting and evaluating methods that calculate and extract the
      most salient phrases for a prediction. The results indicate that CNNs are a valid
      alternative to existing approaches in patient phenotyping and cohort
      identification, and should be further investigated. Moreover, the deep learning
      approach presented in this paper can be used to assist clinicians during chart
      review or support the extraction of billing codes from text by identifying and
      highlighting relevant phrases for various medical conditions.

PMID- 29447189
TI  - Drought response of Mucuna pruriens (L.) DC. inoculated with ACC deaminase and
      IAA producing rhizobacteria.
AB  - Drought is one of the major constraints limiting agricultural production
      worldwide and is expected to increase in the future. Limited water availability
      causes significant effects to plant growth and physiology. Plants have evolved
      different traits to mitigate the stress imposed by drought. The presence of plant
      growth-promoting rhizobacteria (PGPR) could play an important role in improving
      plant performances and productivity under drought. These beneficial
      microorganisms colonize the rhizosphere of plants and increase drought tolerance
      by lowering ethylene formation. In the present study, we demonstrate the
      potential to improve the growth of velvet bean under water deficit conditions of
      two different strains of PGPR with ACCd (1-Aminocyclopropane-1-Carboxylate
      deaminase) activity isolated from rainfed farming system. We compared
      uninoculated and inoculated plants with PGPR to assess: a) photosynthetic
      performance and biomass; b) ACC content and ethylene emission from leaves and
      roots; c) leaf isoprene emission. Our results provided evidence that under
      drought conditions inoculation with PGPR containing the ACCd enzyme could improve
      plant growth compared to untreated plants. Ethylene emission from roots and
      leaves of inoculated velvet bean plants was significantly lower than uninoculated
      plants. Moreover, isoprene emission increased with drought stress progression and
      was higher in inoculated plants compared to uninoculated counterparts. These
      findings clearly illustrate that selected PGPR strains isolated from rainfed
      areas could be highly effective in promoting plant growth under drought
      conditions by decreasing ACC and ethylene levels in plants.

PMID- 29447190
TI  - The incidence and factors of hip fractures and subsequent morbidity in Taiwan: An
      11-year population-based cohort study.
AB  - Hip fractures are a major problem to elder population, but subsequent morbidity
      is unclear about environmental factors and socioeconomic conditions. The study
      aims to investigate the incidence of hip fractures treated by the surgery; to
      compare the sequelae and temporal trends of hip fractures; to evaluate the
      seasonal effects in the subsequent short-term and long-term morbidities after hip
      fractures. A cohort study design is conducted using national health research
      datasets between 2000 and 2010. The ICD-9-CM diagnostic codes were utilized to
      investigate the incidence of hip fractures and the corresponding treatments.
      Hierarchical modeling was used to analyze the factors associated with various
      types of hip fractures. The results indicated that females had a lower incidence
      in the 30-44 age group, but a significantly higher incidence than males among
      those aged 60 years or older (adjusted rates 232.1 vs. 100.3 per 100,000 persons,
      p<0.001). The incidence of hip fractures in the low-income group showed no
      significant difference compared to that in the general population. There was a
      temporal trend of a 8.6% increase in the incidence of all types of hip fractures
      over the period of 2000-2010. A summer-winter variation is observed among the
      elderly. Hip fractures and subsequent morbidity are increasing in Taiwan's aging
      society. Older age, female gender, and time periods were independent risk factors
      for subsequent morbidities after surgical treatment. The result of this study is
      useful to the healthcare policy makers and to raise the public awareness of hip
      fractures.

PMID- 29447191
TI  - Euglena extract suppresses adipocyte-differentiation in human adipose-derived
      stem cells.
AB  - Euglena gracilis Z (Euglena) is a unicellular, photosynthesizing, microscopic
      green alga. It contains several nutrients such as vitamins, minerals, and
      unsaturated fatty acids. In this study, to verify the potential role of Euglena
      consumption on human health and obesity, we evaluated the effect of Euglena on
      human adipose-derived stem cells. We prepared a Euglena extract and evaluated its
      effect on cell growth and lipid accumulation, and found that cell growth was
      promoted by the addition of the Euglena extract. Interestingly, intracellular
      lipid accumulation was inhibited in a concentration-dependent manner.
      Quantitative real-time PCR analysis and western blotting analysis indicated that
      the Euglena extract suppressed adipocyte differentiation by inhibiting the gene
      expression of the master regulators peroxisome proliferator-activated receptor
      gamma (PPARgamma) and one of three CCAAT-enhancer-binding proteins (C/EBPalpha).
      Further Oil Red O staining experiments indicated that the Euglena extract
      inhibited the early stage of adipocyte-differentiation. Consistent with these
      results, we observed that down-regulation of gene expression was involved in the
      early stage of adipogenesis represented by the sterol regulatory element binding
      protein 1 c (SREBP1c), two of three CCAAT-enhancer-binding proteins (C/EBPbeta,
      C/EBPdelta), and the cAMP regulatory element-binding protein (CREB). Taken
      together, these data suggest that Euglena extract is a promising candidate for
      the development of a new therapeutic treatment for obesity.

PMID- 29447192
TI  - Enhancing response coordination through the assessment of response network
      structural dynamics.
AB  - Preparing for intensifying threats of emergencies in unexpected, dangerous, and
      serious natural or man-made events, and consequent management of the situation,
      is highly demanding in terms of coordinating the personnel and resources to
      support human lives and the environment. This necessitates prompt action to
      manage the uncertainties and risks imposed by such extreme events, which requires
      collaborative operation among different stakeholders (i.e., the personnel from
      both the state and local communities). This research aims to find a way to
      enhance the coordination of multi-organizational response operations. To do so,
      this manuscript investigates the role of participants in the formed coordination
      response network and also the emergence and temporal dynamics of the network. By
      analyzing an inter-personal response coordination operation to an extreme
      bushfire event, the networks' and participants' structural change is evaluated
      during the evolution of the operation network over four time durations. The
      results reveal that the coordination response network becomes more decentralized
      over time due to the high volume of communication required to exchange
      information. New emerging communication structures often do not fit the developed
      plans, which stress the need for coordination by feedback in addition to by plan.
      In addition, we find that the participant's brokering role in the response
      operation network identifies a formal and informal coordination role. This is
      useful for comparison of network structures to examine whether what really
      happens during response operations complies with the initial policy.

PMID- 29447194
TI  - Vitro culture of axe-head glochidia in pink heelsplitter Potamilus alatus and
      mechanism of its high host specialists.
AB  - The basal media M199 or MEM was utilized in the classical method of vitro culture
      of glochidia where 1-5% CO2 was required to maintain stable physiological pH for
      completion of non-parasitic metamorphosis. The classical method encounters a
      great challenge to those glochidia which undergo development of visceral tissue
      but significantly increase in size during metamorphosis. The improved in vitro
      culture techniques and classical methods were firstly compared for non-parasitic
      metamorphosis and development of glochidia in pink heelsplitter. Based on the
      improved method, the optimal vitro culture media was further selected from 14
      plasmas or sera, realizing the non-parasitic metamorphosis of axe-head glochidia
      for the first time. The results showed that addition of different plasma (serum)
      had significant effect on glochidial metamorphosis in pink heelsplitter. Only
      glochidia in the skewband grunt and red drum groups could complete metamorphosis,
      the metamorphosis rate in skewband grunt was 93.3+/-3.1% at 24+/-0.5 degrees C,
      significantly higher than in marine and desalinated red drum. Heat-inactivated
      treatment on the plasma of yellow catfish and Barbus capito had significant
      effect on glochidia survival and shell growth. The metamorphosis rate also varied
      among different gravid period, and generally decreased with gravid time. Further
      comparison of free amino acid and fatty acid indicated that the taurine of high
      concentration was the only amino acid that might promote the rapid growth of
      glochidial shell, and the lack of adequate DPA and DHA might be an important
      reason leading to the abnormal foot and visceral development. Combined with our
      results of artificial selection of host fish, we tentatively established the
      mechanism of its host specialists in pink heelsplitter for the first time. This
      is the first report on non-parasite metamorphosis of axe-head glochidia based on
      our improved vitro culture method, which should provide important reference to
      fundamental theory research of glochidia metamorphosis and also benefit for
      better understand of mechanism of host specialists and generalists of Unionidae
      species.

PMID- 29447193
TI  - The quality of instruments to assess the process of shared decision making: A
      systematic review.
AB  - OBJECTIVE: To inventory instruments assessing the process of shared decision
      making and appraise their measurement quality, taking into account the
      methodological quality of their validation studies. METHODS: In a systematic
      review we searched seven databases (PubMed, Embase, Emcare, Cochrane, PsycINFO,
      Web of Science, Academic Search Premier) for studies investigating instruments
      measuring the process of shared decision making. Per identified instrument, we
      assessed the level of evidence separately for 10 measurement properties following
      a three-step procedure: 1) appraisal of the methodological quality using the
      COnsensus-based Standards for the selection of health status Measurement
      INstruments (COSMIN) checklist, 2) appraisal of the psychometric quality of the
      measurement property using three possible quality scores, 3) best-evidence
      synthesis based on the number of studies, their methodological and psychometrical
      quality, and the direction and consistency of the results. The study protocol was
      registered at PROSPERO: CRD42015023397. RESULTS: We included 51 articles
      describing the development and/or evaluation of 40 shared decision-making process
      instruments: 16 patient questionnaires, 4 provider questionnaires, 18 coding
      schemes and 2 instruments measuring multiple perspectives. There is an overall
      lack of evidence for their measurement quality, either because validation is
      missing or methods are poor. The best-evidence synthesis indicated positive
      results for a major part of instruments for content validity (50%) and structural
      validity (53%) if these were evaluated, but negative results for a major part of
      instruments when inter-rater reliability (47%) and hypotheses testing (59%) were
      evaluated. CONCLUSIONS: Due to the lack of evidence on measurement quality, the
      choice for the most appropriate instrument can best be based on the instrument's
      content and characteristics such as the perspective that they assess. We
      recommend refinement and validation of existing instruments, and the use of
      COSMIN-guidelines to help guarantee high-quality evaluations.

PMID- 29447195
TI  - Hydrological and biogeochemical response of the Mediterranean Sea to freshwater
      flow changes for the end of the 21st century.
AB  - We evaluate the changes on the hydrological (temperature and salinity) and
      biogeochemical (phytoplankton biomass) characteristics of the Mediterranean Sea
      induced by freshwater flow modifications under two different scenarios for the
      end of the 21st century. An ensemble of four regional climate model realizations
      using different global circulation models at the boundary and different emission
      scenarios are used to force a single ocean model for the Mediterranean Sea.
      Freshwater flow is modified according to the simulated changes in the
      precipitation rates for the different rivers' catchment regions. To isolate the
      effect resulting from a change in freshwater flow, model results are evaluated
      against a 'baseline' simulation realized assuming a constant inflow equivalent to
      climatologic values. Our model results indicate that sea surface salinity could
      be significantly altered by freshwater flow modification in specific regions and
      that the affected area and the sign of the anomaly are highly dependent on the
      used climate model and emission scenario. Sea surface temperature and
      phytoplankton biomass, on the contrary, show no coherent spatial pattern but a
      rather widespread scattered response. We found in open-water regions a
      significant negative relationship between sea surface temperature anomalies and
      phytoplankton biomass anomalies. This indicates that freshwater flow modification
      could alter the vertical stability of the water column throughout the
      Mediterranean Sea, by changing the strength of vertical mixing and consequently
      upper water fertilization. In coastal regions, however, the correlation between
      sea temperature anomalies and phytoplankton biomass is positive, indicating a
      larger importance of the physiological control of growth rates by temperature.

PMID- 29447196
TI  - Nasopharyngeal carriage of Streptococcus pneumoniae among HIV-infected and 
      uninfected children <5 years of age before introduction of pneumococcal conjugate
      vaccine in Mozambique.
AB  - Nasopharyngeal carriage is a precursor for pneumococcal disease and can be useful
      for evaluating pneumococcal conjugate vaccine (PCV) impact. We studied pre-PCV
      pneumococcal carriage among HIV-infected and -uninfected children in Mozambique.
      Between October 2012 and March 2013, we enrolled HIV-infected children age <5
      years presenting for routine care at seven HIV clinics in 3 sites, including
      Maputo (urban-south), Nampula (urban-north), and Manhica (rural-south). We also
      enrolled a random sample of HIV-uninfected children <5 years old from a
      demographic surveillance site in Manhica. A single nasopharyngeal swab was
      obtained and cultured following enrichment in Todd Hewitt broth with yeast
      extract and rabbit serum. Pneumococcal isolates were serotyped by Quellung
      reaction and multiplex polymerase chain reaction. Factors associated with
      pneumococcal carriage were examined using logistic regression. Overall
      pneumococcal carriage prevalence was 80.5% (585/727), with similar prevalences
      among HIV-infected (81.5%, 339/416) and HIV-uninfected (79.1%, 246/311) children,
      and across age strata. Among HIV-infected, after adjusting for recent antibiotic
      use and hospitalization, there was no significant association between study site
      and colonization: Maputo (74.8%, 92/123), Nampula (83.7%, 82/98), Manhica (84.6%,
      165/195). Among HIV-uninfected, report of having been born to an HIV-infected
      mother was not associated with colonization. Among 601 pneumococcal isolates from
      585 children, serotypes 19F (13.5%), 23F (13.1%), 6A (9.2%), 6B (6.2%) and 19A
      (5.2%) were most common. The proportion of serotypes included in the 10- and 13
      valent vaccines was 44.9% and 61.7%, respectively, with no significant
      differences by HIV status or age group. Overall 36.9% (n = 268) of children were
      colonized with a PCV10 serotype and 49.7% (n = 361) with a PCV13 serotype.
      Pneumococcal carriage was common, with little variation by geographic region,
      age, or HIV status. PCV10 was introduced in April 2013; ongoing carriage studies
      will examine the benefits of PCV10 among HIV-infected and-uninfected children.

PMID- 29447198
TI  - EW-7197 eluting nano-fiber covered self-expandable metallic stent to prevent
      granulation tissue formation in a canine urethral model.
AB  - PURPOSE: To evaluate an EW-7197-eluting nanofiber-covered stent (NFCS) for
      suppressing granulation tissue formation after stent placement in a canine
      urethral model. MATERIALS AND METHODS: All experiments were approved by the
      committee of animal research. A total of 12 NFCSs were placed in the proximal and
      distal urethras of six dogs. Dogs were divided into two groups with 3 dogs each.
      The control stent (CS) group received NFCSs and the drug stent (DS) group
      received EW-7197 (1000 MUg)-eluting NFCSs. All dogs were sacrificed 8 weeks after
      stent placement Histologic findings of the stented urethra were compared using
      the Mann-Whitney U test. RESULTS: Stent placement was technically successful in
      all dogs without procedure-related complications. On urethrographic analysis, the
      mean luminal diameter was significantly larger in the DS group than in the CS
      group at 4 and 8 weeks after stent placement (all p < 0.001). On histological
      examination, mean thicknesses of the papillary projection, thickness of
      submucosal fibrosis, number of epithelial layers, and degree of collagen
      deposition were significantly lower in the DS group than in the CS group (all p <
      0.001), whereas the mean degree of inflammatory cell infiltration was not
      significantly different (p > 0.05). CONCLUSION: The EW-7197-eluting NFCS is
      effective and safe for suppressing granulation tissue formation after stent
      placement in a canine urethral model.

PMID- 29447197
TI  - Shotgun proteomics deciphered age/division of labor-related functional
      specification of three honeybee (Apis mellifera L.) exocrine glands.
AB  - The honeybee (Apis mellifera L.) uses various chemical signals produced by the
      worker exocrine glands to maintain the functioning of its colony. The roles of
      worker postcerebral glands (PcGs), thoracic glands (TGs), and mandibular glands
      (MGs) and the functional changes they undergo according to the division of labor
      from nursing to foraging are not as well studied. To comprehensively characterize
      the molecular roles of these glands in workers and their changes according to the
      division of labor of workers, we analyzed the proteomes of PcGs, TGs, and MGs
      from nurse bees and foragers using shotgun proteomics technology. We identified
      approximately 2000 proteins from each of the nurse bee or forager glands and
      highlighted the features of these glands at the molecular level by
      semiquantitative enrichment analyses of frequently detected, gland-selective, and
      labor-selective proteins. First, we found the high potential to produce lipids in
      PcGs and MGs, suggesting their relation to pheromone production. Second, we also
      found the proton pumps abundant in TGs and propose some transporters possibly
      related to the saliva production. Finally, our data unveiled candidate enzymes
      involved in labor-dependent acid production in MGs.

PMID- 29447200
TI  - Discovery of two new species of Crotalaria (Leguminosae, Crotalarieae) from
      Western Ghats, India.
AB  - Two new species of Fabaceae-Papilionoideae are described and illustrated.
      Crotalaria suffruticosa from Karul Ghat region of Maharashtra is morphologically
      close to C. albida and C. epunctata. C. multibracteata from Panhala region of
      Maharashtra resembles C. vestita. C. suffruticosa differs from C. albida and C.
      epunctata in its habit, leaf, inflorescence, callosity, keel type, stigma, style
      morphology and number of seeds/pod. To test if the new species differ from their
      morphologically most similar species, we measured various traits and performed a
      Principal Component Analysis (PCA). This analysis shows that the new species
      differs from similar species in gross morphology for several diagnostic traits
      and showed correlations between the variables or distance among groups and
      estimated the contribution of each character. Phylogenetic analyses were also
      conducted based on nuclear (ITS) and plastid (matK) markers. The analyses
      revealed nucleotide differences between the new species and their close allies
      attributing to their distinctiveness. A map and key including all species of
      Crotalaria from Maharashtra state are provided. Conservation status of the two
      new species have also been assessed.

PMID- 29447199
TI  - Short-term repeated HRV-16 exposure results in an attenuated immune response in
      vivo in humans.
AB  - INTRODUCTION: Naturally, development of adaptive immunity following HRV infection
      affects the immune response. However, it is currently unclear whether or not HRV
      re-exposure within a short time frame leads to an altered innate immune response.
      The "experimental cold model" is used to investigate the pathogenesis of HRV
      infection and allows us to investigate the effects of repeated exposure on both
      local and systemic innate immunity. METHODS: 40 healthy male and female (1:1)
      subjects were nasally inoculated with HRV-16 or placebo. One week later, all
      subjects received HRV-16. Baseline seronegative subjects (n = 18) were included
      for further analysis. RESULTS: Infection rate was 82%. Primary HRV infection
      induced a marked increase in viral load and IP-10 levels in nasal wash, while a
      similar trend was observed for IL-6 and IL-10. Apart from an increase in IP-10
      plasma levels, HRV infection did not induce systemic immune effects nor lower
      respiratory tract inflammation. With similar viral load present during the second
      HRV challenge, IP-10 and IL-6 in nasal wash showed no increase, but gradually
      declined, with a similar trend for IL-10. CONCLUSION: Upon a second HRV challenge
      one week after the first, a less pronounced response for several innate immune
      parameters is observed. This could be the result of immunological tolerance and
      possibly increases vulnerability towards secondary infections.

PMID- 29447201
TI  - Estimation model for habitual 24-hour urinary-sodium excretion using simple
      questionnaires from normotensive Koreans.
AB  - This study was conducted to develop an equation for estimation of 24-h urinary
      sodium excretion that can serve as an alternative to 24-h dietary recall and 24-h
      urine collection for normotensive Korean adults. In total, data on 640 healthy
      Korean adults aged 19 to 69 years from 4 regions of the country were collected as
      a training set. In order to externally validate the equation developed from that
      training set, 200 subjects were recruited independently as a validation set. Due
      to heterogeneity by gender, we constructed a gender-specific equation for
      estimation of 24-h urinary-sodium excretion by using a multivariable linear
      regression model and assessed the performance of the developed equation in
      validation set. The best model consisted of age, body weight, dietary behavior
      ('eating salty food', 'Kimchi consumption', 'Korean soup or stew consumption',
      'soy sauce or red pepper paste consumption'), and smoking status in men, and age,
      body weight, dietary behavior ('salt preference', 'eating salty food', 'checking
      sodium content for processed foods', 'nut consumption'), and smoking status in
      women, respectively. When this model was tested in the external validation set,
      the mean bias between the measured and estimated 24-h urinary-sodium excretion
      from Bland-Altman plots was -1.92 (95% CI: -113, 110) mmol/d for men and -1.51
      (95% CI: -90.6, 87.6) mmol/d for women. The cut-points of sodium intake
      calculated based on the equations were >=4,000 mg/d for men and >=3,500 mg/d for
      women, with 89.8 and 76.6% sensitivity and 29.3 and 64.2% specificity,
      respectively. In this study, a habitual 24-hour urinary-sodium-excretion
      estimation model of normotensive Korean adults based on anthropometric and
      lifestyle factors was developed and showed feasibility for an asymptomatic
      population.

PMID- 29447202
TI  - Nitrogen isotopes suggest a change in nitrogen dynamics between the Late
      Pleistocene and modern time in Yukon, Canada.
AB  - A magnificent repository of Late Pleistocene terrestrial megafauna fossils is
      contained in ice-rich loess deposits of Alaska and Yukon, collectively eastern
      Beringia. The stable carbon (delta13C) and nitrogen (delta15N) isotope
      compositions of bone collagen from these fossils are routinely used to determine
      paleodiet and reconstruct the paleoecosystem. This approach requires
      consideration of changes in C- and N-isotope dynamics over time and their effects
      on the terrestrial vegetation isotopic baseline. To test for such changes between
      the Late Pleistocene and modern time, we compared delta13C and delta15N for
      vegetation and bone collagen and structural carbonate of some modern, Yukon,
      arctic ground squirrels with vegetation and bones from Late Pleistocene fossil
      arctic ground squirrel nests preserved in Yukon loess deposits. The isotopic
      discrimination between arctic ground squirrel bone collagen and their diet was
      measured using modern samples, as were isotopic changes during plant
      decomposition; Over-wintering decomposition of typical vegetation following
      senescence resulted in a minor change (~0-1 0/00) in delta13C of modern Yukon
      grasses. A major change (~2-10 0/00) in delta15N was measured for decomposing
      Yukon grasses thinly covered by loess. As expected, the collagen-diet C-isotope
      discrimination measured for modern samples confirms that modern vegetation
      delta13C is a suitable proxy for the Late Pleistocene vegetation in Yukon
      Territory, after correction for the Suess effect. The N-isotope composition of
      vegetation from the fossil arctic ground squirrel nests, however, is determined
      to be ~2.8 0/00 higher than modern grasslands in the region, after correction for
      decomposition effects. This result suggests a change in N dynamics in this region
      between the Late Pleistocene and modern time.

PMID- 29447203
TI  - Quantification of fetal organ volume and fat deposition following in utero
      exposure to maternal Western Diet using MRI.
AB  - PURPOSE: To examine the feasibility of using MRI to identify differences in liver
      size and fat deposition in fetal guinea pigs exposed to an in utero environment
      influenced by maternal consumption of a Western diet. MATERIALS AND METHODS:
      Female guinea pigs fed either an energy-dense Western Diet (WD), comprised of
      increased saturated fats and simple sugars, or a Control Diet (CD) from weaning
      through pregnancy, underwent MR scanning near term (~ 60 days; term ~ 69 days).
      Maternal weights were collected at mating and at MR scanning. T1-weighted, T2
      weighted, and IDEAL water-fat images were acquired at 3 Tesla. The images were
      used to segment maternal adipose tissue, fetal liver, fetal brain, fetal adipose
      tissue, and total fetal volumes and to measure maternal and fetal hepatic fat
      fractions. RESULTS: Weights of WD sows were lower prior to pregnancy (P = .04),
      however their weight gain over pregnancy did not differ from the CD group (P =
      .98). The WD sows had less total adipose tissue (TAT) at MR scanning (P = .04),
      while hepatic fat content was significantly elevated (P = .04). When controlling
      for litter size, WD fetuses had larger livers (P = .02), smaller brains (P =
      .01), and increased total adipose tissue volume (P = .01) when normalized by
      fetal volume. The WD fetuses also had increased hepatic fat fractions compared to
      CD fetal livers (P < .001). CONCLUSION: Maternal Western Diet consumption prior
      to and during pregnancy induces differences in maternal liver fat content, fetal
      liver volume and liver fat storage, as well as changes in fetal adipose tissue
      deposition that can be measured in utero using MRI.

PMID- 29447204
TI  - Comparison of viral infection in healthcare-associated pneumonia (HCAP) and
      community-acquired pneumonia (CAP).
AB  - BACKGROUND: Although viruses are known to be the second most common etiological
      factor in community-acquired pneumonia (CAP), the respiratory viral profile of
      the patients with healthcare-associated pneumonia (HCAP) has not yet been
      elucidated. We investigated the prevalence and the clinical impact of respiratory
      virus infection in adult patients with HCAP. METHODS: Patients admitted with HCAP
      or CAP, between January and December 2016, to a tertiary referral hospital in
      Korea, were prospectively enrolled, and virus identification was performed using
      reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: Among 452
      enrolled patients (224 with HCAP, 228 with CAP), samples for respiratory viruses
      were collected from sputum or endotracheal aspirate in 430 (95.1%) patients and
      from nasopharyngeal specimens in 22 (4.9%) patients. Eighty-seven (19.2%)
      patients had a viral infection, and the proportion of those with viral infection
      was significantly lower in the HCAP than in the CAP group (13.8% vs 24.6%, p =
      0.004). In both the HCAP and CAP groups, influenza A was the most common
      respiratory virus, followed by entero-rhinovirus. The seasonal distributions of
      respiratory viruses were also similar in both groups. In the HCAP group, the
      viral infection resulted in a similar length of hospital stay and in-hospital
      mortality as viral-bacterial coinfection and bacterial infection, and the CAP
      group showed similar results. CONCLUSIONS: The prevalence of viral infection in
      patients with HCAP was lower than that in patients with CAP, and resulted in a
      similar prognosis as viral-bacterial coinfection or bacterial infection.

PMID- 29447205
TI  - Aggressive fluid accumulation is associated with acute kidney injury and
      mortality in a cohort of patients with severe pneumonia caused by influenza A
      H1N1 virus.
AB  - INTRODUCTION: Fluid accumulation is associated with adverse outcomes such as
      acute kidney injury (AKI) in critically ill patients. This study aimed to
      describe the factors associated with AKI in individuals with influenza A H1N1
      severe pneumonia, and explore the relation of fluid accumulation with AKI and
      mortality. MATERIAL AND METHODS: We reviewed medical records of individuals with
      influenza A H1N1 severe pneumonia and no history of chronic kidney disease,
      attending a national referral center for respiratory diseases between November
      2014 and May 2015. Demographic information, risk factors for AKI, physiologic and
      laboratory data, outcomes and information on fluid intake and output were
      recorded. Categorical variables were compared using the chi-square test.
      Quantitative variables were compared using the Mann-Whitney test. Factors
      associated with AKI and mortality were identified by binary logistic regression.
      Linear models of fluid accumulation rates for individuals and groups were
      estimated using segmented linear regression. RESULTS: Of 60 patients studied, 43
      developed AKI (71.6%). Male gender was protective for AKI (p = 0.019). AKI was
      associated with nephrotoxic drugs (p = 0.016); PEEP>10 cm H2O on admission (p =
      0.031); mortality (p = 0.037); and fluid accumulation >=10% (fluid overload) at
      day 7 of hospitalization (p = 0.00026). Mortality was associated with older age
      (p = 0.009); nephrotoxic drugs (p = 0.034); and higher Pneumonia Severity Index
      score (112 vs. 76, p = 0.008) on admission. The Deceased-AKI group had a higher
      rate of fluid accumulation (expressed as ml/kg/body weight) than the Survivors-No
      AKI group during the study period of 7 days (Survivors-No AKI = 13.31 vs.
      Deceased-AKI = 22.76, p = 0.019). During the highest phase of fluid accumulation,
      the Survivors-No AKI group had a slower rate of fluid accumulation than the
      Survivors-AKI group (14.91 vs. 28.49, p = 0.001). CONCLUSIONS: A high rate of
      fluid accumulation was associated with AKI and mortality. We support the approach
      of resuscitation in acute illness, with an early transition to neutral and then
      negative fluid balances.

PMID- 29447206
TI  - Multiplex CRISPR/Cas9 system impairs HCMV replication by excising an essential
      viral gene.
AB  - Anti-HCMV treatments used in immunosuppressed patients reduce viral replication,
      but resistant viral strains can emerge. Moreover, these drugs do not target
      latently infected cells. We designed two anti-viral CRISPR/Cas9 strategies to
      target the UL122/123 gene, a key regulator of lytic replication and reactivation
      from latency. The singleplex strategy contains one gRNA to target the start
      codon. The multiplex strategy contains three gRNAs to excise the complete
      UL122/123 gene. Primary fibroblasts and U-251 MG cells were transduced with
      lentiviral vectors encoding Cas9 and one or three gRNAs. Both strategies induced
      mutations in the target gene and a concomitant reduction of immediate early (IE)
      protein expression in primary fibroblasts. Further detailed analysis in U-251 MG
      cells showed that the singleplex strategy induced 50% of indels in the viral
      genome, leading to a reduction in IE protein expression. The multiplex strategy
      excised the IE gene in 90% of all viral genomes and thus led to the inhibition of
      IE protein expression. Consequently, viral genome replication and late protein
      expression were reduced by 90%. Finally, the production of new viral particles
      was nearly abrogated. In conclusion, the multiplex anti-UL122/123 CRISPR/Cas9
      system can target the viral genome efficiently enough to significantly prevent
      viral replication.

PMID- 29447207
TI  - Demography of a forest elephant population.
AB  - African forest elephants face severe threats from illegal killing for ivory and
      bushmeat and habitat conversion. Due to their cryptic nature and inaccessible
      range, little information on the biology of this species has been collected
      despite its iconic status. Compiling individual based monitoring data collected
      over 20 years from the Dzanga Bai population in Central African Republic, we
      summarize sex and age specific survivorship and female age specific fecundity for
      a cohort of 1625 individually identified elephants. Annual mortality (average =
      3.5%) and natality (average = 5.3%) were lower and markedly less variable
      relative to rates reported for savanna elephant populations. New individuals
      consistently entered the study system, leading to a 2.5% average annual increase
      in the registered population. Calf sex ratios among known birth did not differ
      from parity. A weak seasonal signal in births was detected suggesting increased
      conceptions during the wet season. Inter-calf intervals and age of primiparity
      were longer relative to savanna elephant populations. Within the population,
      females between the ages of 25-39 demonstrated the shortest inter-calf intervals
      and highest fecundity, and previous calf sex had no influence on the interval.
      Calf survivorship was high (97%) the first two years after birth and did not
      differ by sex. Male and female survival began to differ by the age of 13 years,
      and males demonstrated significantly lower survival relative to females by the
      age of 20. It is suspected these differences are driven by human selection for
      ivory. Forest elephants were found to have one of the longest generation times
      recorded for any species at 31 years. These data provide fundamental
      understanding of forest elephant demography, providing baseline data for
      projecting population status and trends.

PMID- 29447209
TI  - Haplotype-based genome-wide association study identifies loci and candidate genes
      for milk yield in Holsteins.
AB  - Since milk yield is a highly important economic trait in dairy cattle, the genome
      wide association study (GWAS) is vital to explain the genetic architecture
      underlying milk yield and to perform marker-assisted selection (MAS). In this
      study, we adopted a haplotype-based empirical Bayesian GWAS to identify the loci
      and candidate genes for milk yield. A total of 1 092 Holstein cows were sequenced
      by using the genotyping by genome reducing and sequencing (GGRS) method. After
      filtering, 164 312 high-confidence SNPs and 13 476 haplotype blocks were
      identified to use for GWAS. The results indicated that 17 blocks were
      significantly associated with milk yield. We further identified the nearest gene
      of each haplotype block and annotated the genes with milk-associated quantitative
      trait locus (QTL) intervals and ingenuity pathway analysis (IPA) networks. Our
      analysis showed that four genes, DLGAP1, AP2B1, ITPR2 and THBS4, have
      relationships with milk yield, while another three, ARHGEF4, TDRD1 and KIF19,
      were inferred to have potential relationships. Additionally, a network derived
      from the IPA containing one inferred (ARHGEF4) and all four confirmed genes
      likely regulates milk yield. Our findings add to the understanding of identifying
      the causal genes underlying milk production traits and could guide follow up
      studies for further confirmation of the associated genes, pathways and biological
      networks.

PMID- 29447208
TI  - Species-specific regulation of angiogenesis by glucocorticoids reveals
      contrasting effects on inflammatory and angiogenic pathways.
AB  - Glucocorticoids are potent inhibitors of angiogenesis in the rodent in vivo and
      in vitro but the mechanism by which this occurs has not been determined.
      Administration of glucocorticoids is used to treat a number of conditions in
      horses but the angiogenic response of equine vessels to glucocorticoids and,
      therefore, the potential role of glucocorticoids in pathogenesis and treatment of
      equine disease, is unknown. This study addressed the hypothesis that
      glucocorticoids would be angiostatic both in equine and murine blood vessels.The
      mouse aortic ring model of angiogenesis was adapted to assess the effects of
      cortisol in equine vessels. Vessel rings were cultured under basal conditions or
      exposed to: foetal bovine serum (FBS; 3%); cortisol (600 nM), cortisol (600nM)
      plus FBS (3%), cortisol (600nM) plus either the glucocorticoid receptor
      antagonist RU486 or the mineralocorticoid receptor antagonist spironolactone. In
      murine aortae cortisol inhibited and FBS stimulated new vessel growth. In
      contrast, in equine blood vessels FBS alone had no effect but cortisol alone, or
      in combination with FBS, dramatically increased new vessel growth compared with
      controls. This effect was blocked by glucocorticoid receptor antagonism but not
      by mineralocorticoid antagonism. The transcriptomes of murine and equine
      angiogenesis demonstrated cortisol-induced down-regulation of inflammatory
      pathways in both species but up-regulation of pro-angiogenic pathways selectively
      in the horse. Genes up-regulated in the horse and down-regulated in mice were
      associated with the extracellular matrix. These data call into question our
      understanding of glucocorticoids as angiostatic in every species and may be of
      clinical relevance in the horse.

PMID- 29447210
TI  - Functional imaging of the interaction between gut microbiota and the human host:
      A proof-of-concept clinical study evaluating novel use for 18F-FDG PET-CT.
AB  - Recent data comparing germ-free to conventionally-raised mice demonstrated that
      energy homeostasis of colonocytes is dependent on gut microbiota through
      regulation of short chain fatty acids (SCFA) production and glucose utilization.
      We sought to evaluate 18F-FDG PET-CT as a novel technique for functional imaging
      of alterations in glucose metabolism as a result of the interaction between the
      gut microbiota and the human host. We conducted a prospective study in healthy
      humans that underwent 18F-FDG PET-CT and sampling of the gut microbiota before
      and after orally administered broad-spectrum antibiotics. The primary outcomes
      were total and regional physiologic colonic 18F-FDG uptake (measured as the mean
      and max standardized uptake values [SUVmean and SUVmax]). The study demonstrated
      significant increases in physiologic colonic 18F-FDG uptake in all study
      participants following antibiotic treatment and a 4-5log reduction of gut
      bacterial load. The mean increase in SUVmax was 0.63+/-0.37 SD (p = 0.004) and
      the median increase was 0.42 with an IQR of 0.40-0.81. The mean increase in
      SUVmean was 0.31+/-0.24 SD (p = 0.01) and the median increase was 0.41 with an
      IQR of 0.06-0.55. A likely explanation for this phenomenon is a shift in
      colonocyte metabolism to glycolysis due to a shortage of SCFA.

PMID- 29447211
TI  - Malaria severity: Possible influence of the E670G PCSK9 polymorphism: A
      preliminary case-control study in Malian children.
AB  - AIM: Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a hepatic secretory
      protein which promotes the degradation of low-density lipoprotein receptors
      leading to reduced hepatic uptake of plasma cholesterol. Non-synonymous single
      nucleotide polymorphisms in its gene have been linked to hypo- or hyper-
      cholesterolemia, depending on whether they decrease or increase PCSK9 activity,
      respectively. Since the proliferation and the infectivity of Plasmodium spp.
      partially depend on cholesterol from the host, we hypothesize that these PCSK9
      genetic polymorphisms could influence the course of malaria infection in
      individuals who carry them. Here we examined the frequency distribution of one
      dominant (C679X) and two recessive (A443T, I474V) hypocholesterolemic
      polymorphisms as well as that of one recessive hypercholesterolemic polymorphism
      (E670G) among healthy and malaria-infected Malian children. METHODS: Dried blood
      spots were collected in Bandiagara, Mali, from 752 age, residence and ethnicity
      matched children: 253 healthy controls, 246 uncomplicated malaria patients and
      253 severe malaria patients. Their genomic DNA was extracted and genotyped for
      the above PCSK9 polymorphisms using Taqman assays. Associations of genotype
      distributions and allele frequencies with malaria were evaluated. RESULTS: The
      minor allele frequency of the A443T, I474V, E670G, and C679X polymorphisms in the
      study population sample was 0.12, 0.20, 0.26, and 0.02, respectively. For each
      polymorphism, the genotype distribution among the three health conditions was
      statistically insignificant, but for the hypercholesterolemic E670G polymorphism,
      a trend towards association of the minor allele with malaria severity was
      observed (P = 0.035). The association proved to be stronger when allele
      frequencies between healthy controls and severe malaria cases were compared (Odd
      Ratio: 1.34; 95% Confidence Intervals: 1.04-1.83); P = 0.031). CONCLUSIONS:
      Carriers of the minor allele of the E670G PCSK9 polymorphism might be more
      susceptible to severe malaria. Further investigation of the cholesterol
      regulating function of PCSK9 in the pathophysiology of malaria is needed.

PMID- 29447212
TI  - Predicting species emergence in simulated complex pre-biotic networks.
AB  - An intriguing question in evolution is what would happen if one could "replay"
      life's tape. Here, we explore the following hypothesis: when replaying the tape,
      the details ("decorations") of the outcomes would vary but certain "invariants"
      might emerge across different life-tapes sharing similar initial conditions. We
      use large-scale simulations of an in silico model of pre-biotic evolution called
      GARD (Graded Autocatalysis Replication Domain) to test this hypothesis. GARD
      models the temporal evolution of molecular assemblies, governed by a rates matrix
      (i.e. network) that biases different molecules' likelihood of joining or leaving
      a dynamically growing and splitting assembly. Previous studies have shown the
      emergence of so called compotypes, i.e., species capable of replication and
      selection response. Here, we apply networks' science to ascertain the degree to
      which invariants emerge across different life-tapes under GARD dynamics and
      whether one can predict these invariant from the chemistry specification alone
      (i.e. GARD's rates network representing initial conditions). We analysed the
      (complex) rates' network communities and asked whether communities are related
      (and how) to the emerging species under GARD's dynamic, and found that the
      communities correspond to the species emerging from the simulations. Importantly,
      we show how to use the set of communities detected to predict species emergence
      without performing any simulations. The analysis developed here may impact
      complex systems simulations in general.

PMID- 29447213
TI  - Delineating and identifying long-term changes in the whooping crane (Grus
      americana) migration corridor.
AB  - Defining and identifying changes to seasonal ranges of migratory species is
      required for effective conservation. Historic sightings of migrating whooping
      cranes (Grus americana) have served as sole source of information to define a
      migration corridor in the Great Plains of North America (i.e., Canadian Prairies
      and United States Great Plains) for this endangered species. We updated this
      effort using past opportunistic sightings from 1942-2016 (n = 5,055) and more
      recent (2010-2016) location data from 58 telemetered birds (n = 4,423) to
      delineate migration corridors that included 50%, 75%, and 95% core areas. All
      migration corridors were well defined and relatively compact, with the 95% core
      corridor averaging 294 km wide, although it varied approximately +/-40% in width
      from 170 km in central Texas to 407 km at the international border of the United
      States and Canada. Based on historic sightings and telemetry locations, we
      detected easterly movements in locations over time, primarily due to locations
      west of the median shifting east. This shift occurred from northern Oklahoma to
      central Saskatchewan at an average rate of 1.2 km/year (0.3-2.8 km/year).
      Associated with this directional shift was a decrease in distance of locations
      from the median in the same region averaging -0.7 km/year (-0.3--1.3 km/year),
      suggesting a modest narrowing of the migration corridor. Changes in the corridor
      over the past 8 decades suggest that agencies and organizations interested in
      recovery of this species may need to modify where conservation and recovery
      actions occur. Whooping cranes showed apparent plasticity in their migratory
      behavior, which likely has been necessary for persistence of a wetland-dependent
      species migrating through the drought-prone Great Plains. Behavioral flexibility
      will be useful for whooping cranes to continue recovery in a future of uncertain
      climate and land use changes throughout their annual range.

PMID- 29447214
TI  - High efficiency classification of children with autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a wide-ranging collection of developmental
      diseases with varying symptoms and degrees of disability. Currently, ASD is
      diagnosed mainly with psychometric tools, often unable to provide an early and
      reliable diagnosis. Recently, biochemical methods are being explored as a means
      to meet the latter need. For example, an increased predisposition to ASD has been
      associated with abnormalities of metabolites in folate-dependent one carbon
      metabolism (FOCM) and transsulfuration (TS). Multiple metabolites in the FOCM/TS
      pathways have been measured, and statistical analysis tools employed to identify
      certain metabolites that are closely related to ASD. The prime difficulty in such
      biochemical studies comes from (i) inefficient determination of which metabolites
      are most important and (ii) understanding how these metabolites are collectively
      related to ASD. This paper presents a new method based on scores produced in
      Support Vector Machine (SVM) modeling combined with High Dimensional Model
      Representation (HDMR) sensitivity analysis. The new method effectively and
      efficiently identifies the key causative metabolites in FOCM/TS pathways, ranks
      their importance, and discovers their independent and correlative action patterns
      upon ASD. Such information is valuable not only for providing a foundation for a
      pathological interpretation but also for potentially providing an early, reliable
      diagnosis ideally leading to a subsequent comprehensive treatment of ASD. With
      only tens of SVM model runs, the new method can identify the combinations of the
      most important metabolites in the FOCM/TS pathways that lead to ASD. Previous
      efforts to find these metabolites required hundreds of thousands of model runs
      with the same data.

PMID- 29447215
TI  - Maternal high-fat diet associated with altered gene expression, DNA methylation,
      and obesity risk in mouse offspring.
AB  - We investigated maternal obesity in inbred SM/J mice by assigning females to a
      high-fat diet or a low-fat diet at weaning, mating them to low-fat-fed males,
      cross-fostering the offspring to low-fat-fed SM/J nurses at birth, and weaning
      the offspring onto a high-fat or low-fat diet. A maternal high-fat diet
      exacerbated obesity in the high-fat-fed daughters, causing them to weigh more,
      have more fat, and have higher serum levels of leptin as adults, accompanied by
      dozens of gene expression changes and thousands of DNA methylation changes in
      their livers and hearts. Maternal diet particularly affected genes involved in
      RNA processing, immune response, and mitochondria. Between one-quarter and one
      third of differentially expressed genes contained a differentially methylated
      region associated with maternal diet. An offspring high-fat diet reduced overall
      variation in DNA methylation, increased body weight and organ weights, increased
      long bone lengths and weights, decreased insulin sensitivity, and changed the
      expression of 3,908 genes in the liver. Although the offspring were more affected
      by their own diet, their maternal diet had epigenetic effects lasting through
      adulthood, and in the daughters these effects were accompanied by phenotypic
      changes relevant to obesity and diabetes.

PMID- 29447216
TI  - Genome mining of Streptomyces scabrisporus NF3 reveals symbiotic features
      including genes related to plant interactions.
AB  - Endophytic bacteria are wide-spread and associated with plant physiological
      benefits, yet their genomes and secondary metabolites remain largely
      unidentified. In this study, we explored the genome of the endophyte Streptomyces
      scabrisporus NF3 for discovery of potential novel molecules as well as genes and
      metabolites involved in host interactions. The complete genomes of seven
      Streptomyces and three other more distantly related bacteria were used to define
      the functional landscape of this unique microbe. The S. scabrisporus NF3 genome
      is larger than the average Streptomyces genome and not structured for an obligate
      endosymbiotic lifestyle; this and the fact that can grow in R2YE media implies
      that it could include a soil-living stage. The genome displays an enrichment of
      genes associated with amino acid production, protein secretion, secondary
      metabolite and antioxidants production and xenobiotic degradation, indicating
      that S. scabrisporus NF3 could contribute to the metabolic enrichment of soil
      microbial communities and of its hosts. Importantly, besides its metabolic
      advantages, the genome showed evidence for differential functional specificity
      and diversification of plant interaction molecules, including genes for the
      production of plant hormones, stress resistance molecules, chitinases,
      antibiotics and siderophores. Given the diversity of S. scabrisporus mechanisms
      for host upkeep, we propose that these strategies were necessary for its
      adaptation to plant hosts and to face changes in environmental conditions.

PMID- 29447218
TI  - FindPrimaryPairs: An efficient algorithm for predicting element-transferring
      reactant/product pairs in metabolic networks.
AB  - The metabolism of individual organisms and biological communities can be viewed
      as a network of metabolites connected to each other through chemical reactions.
      In metabolic networks, chemical reactions transform reactants into products,
      thereby transferring elements between these metabolites. Knowledge of how
      elements are transferred through reactant/product pairs allows for the
      identification of primary compound connections through a metabolic network.
      However, such information is not readily available and is often challenging to
      obtain for large reaction databases or genome-scale metabolic models. In this
      study, a new algorithm was developed for automatically predicting the element
      transferring reactant/product pairs using the limited information available in
      the standard representation of metabolic networks. The algorithm demonstrated
      high efficiency in analyzing large datasets and provided accurate predictions
      when benchmarked with manually curated data. Applying the algorithm to the
      visualization of metabolic networks highlighted pathways of primary
      reactant/product connections and provided an organized view of element
      transferring biochemical transformations. The algorithm was implemented as a new
      function in the open source software package PSAMM in the release v0.30
      (https://zhanglab.github.io/psamm/).

PMID- 29447217
TI  - Does napping enhance the effects of Cognitive Bias Modification-Appraisal
      training? An experimental study.
AB  - Posttraumatic Stress Disorder (PTSD) is characterised by dysfunctional appraisals
      of the trauma and its consequences including one's own symptoms. Experimental
      studies have shown that Cognitive Bias Modification-Appraisal (CBM-App) training
      can reduce dysfunctional interpretations and analog trauma symptoms. One
      important question is how to enhance the effects of CBM-App. Following work
      suggesting that sleep has beneficial effects on consolidation processes and can
      thus improve learning, the present study investigated whether a brief period of
      sleep (i.e., a nap) enhances the effects of CBM-App. All participants watched a
      stressful movie as an analogue trauma induction. After that, participants
      received either positive or negative CBM-App training. Within each training, half
      of the participants then had a 90-minute nap or watched a neutral movie. Results
      showed that the CBM training induced training-congruent appraisals. Sleep did not
      enhance this effect. Participants who slept, however, experienced fewer intrusive
      memories of the analogue trauma, but this effect was independent of the CBM
      condition. These results provide valuable information about the effects of sleep
      during a 90-minute nap period on encoding of analogue trauma and emotional
      learning in the context of appraisal, and highlight the importance of sleep as a
      focus for continued research.

PMID- 29447219
TI  - Optimization of prophylaxis for hemophilia A.
AB  - BACKGROUND & AIMS: Prophylactic injections of factor VIII reduce the incidence of
      bleeds and slow the development of joint damage in people with hemophilia. The
      aim of this study was to identify optimal person-specific prophylaxis regimens
      for children with hemophilia A. METHODS: Analytic and numerical methods were used
      to identify prophylaxis regimens which maximize the time for which plasma factor
      VIII concentrations exceed a threshold, maximize the lowest plasma factor VIII
      concentrations, and minimize risk of bleeds. RESULTS: It was demonstrated
      analytically that, for any injection schedule, the regimen that maximizes the
      lowest factor VIII concentration involves sharing doses between injections so
      that all of the trough concentrations in a prophylaxis cycle are equal. Numerical
      methods were used to identify optimal prophylaxis schedules and explore the trade
      offs between efficacy and acceptability of different prophylaxis regimens. The
      prophylaxis regimen which minimizes risk of bleeds depends on the person's
      pattern of physical activity and may differ greatly from prophylaxis regimens
      that optimize pharmacokinetic parameters. Prophylaxis regimens which minimize
      risk of bleeds also differ from prophylaxis regimens that are typically
      prescribed. Predictions about which regimen is optimal are sensitive to estimates
      of the effects on risk of bleeds of factor VIII concentration and physical
      activity. CONCLUSION: The methods described here can be used to identify optimal,
      person-specific prophylaxis regimens for children with hemophilia A.

PMID- 29447220
TI  - The relationship between context, structure, and processes with outcomes of 6
      regional diabetes networks in Europe.
AB  - BACKGROUND: While health service provisioning for the chronic condition Type 2
      Diabetes (T2D) often involves a network of organisations and professionals, most
      evidence on the relationships between the structures and processes of service
      provisioning and the outcomes considers single organisations or solo
      practitioners. Extending Donabedian's Structure-Process-Outcome (SPO) model, we
      investigate how differences in quality of life, effective coverage of diabetes,
      and service satisfaction are associated with differences in the structures,
      processes, and context of T2D services in six regions in Finland, Germany,
      Greece, Netherlands, Spain, and UK. METHODS: Data collection consisted of: a)
      systematic modelling of provider network's structures and processes, and b) a
      cross-sectional survey of patient reported outcomes and other information. The
      survey resulted in data from 1459 T2D patients, during 2011-2012. Stepwise linear
      regression models were used to identify how independent cumulative proportion of
      variance in quality of life and service satisfaction are related to differences
      in context, structure and process. The selected context, structure and process
      variables are based on Donabedian's SPO model, a service quality research
      instrument (SERVQUAL), and previous organization and professional level evidence.
      Additional analysis deepens the possible bidirectional relation between outcomes
      and processes. RESULTS: The regression models explain 44% of variance in service
      satisfaction, mostly by structure and process variables (such as human resource
      use and the SERVQUAL dimensions). The models explained 23% of variance in quality
      of life between the networks, much of which is related to contextual variables.
      Our results suggest that effectiveness of A1c control is negatively correlated
      with process variables such as total hours of care provided per year and cost of
      services per year. CONCLUSIONS: While the selected structure and process
      variables explain much of the variance in service satisfaction, this is less the
      case for quality of life. Moreover, it appears that the effect of the clinical
      outcome A1c control on processes is stronger than the other way around, as poorer
      control seems to relate to more service use, and higher cost. The standardized
      operational models used in this research prove to form a basis for expanding the
      network level evidence base for effective T2D service provisioning.

PMID- 29447221
TI  - How does the interaction radius affect the performance of intervention on
      collective behavior?
AB  - The interaction radius r plays an important role in the collective behavior of
      many multi-agent systems because it defines the interaction network among agents.
      For the topic of intervention on collective behavior of multi-agent systems, does
      r also affect the intervention performance? In this paper we study whether it is
      easier to change the convergent heading of the group by adding some special
      agents (called shills) into the Vicsek model when r is larger (or smaller). Two
      kinds of shills are considered: fixed-heading shills (like leaders that never
      change their headings) and evolvable-heading shills (like normal agents but with
      carefully designed initial headings). We know that with the increase of r, two
      contradictory effects exist simultaneously: the influential area of a single
      shill is enlarged, but its influence strength is weakened. Which factor
      dominates? Through simulations and theoretical analysis we surprisingly find that
      r affects the intervention performance differently in different cases: when fixed
      heading shills are placed together at the center of the group, larger r gives a
      better intervention performance; when evolvable-heading shills are placed
      together at the center, smaller r is better; when shills (either fixed-heading or
      evolvable-heading) are distributed evenly inside the group, the effect of r on
      the intervention performance is not significant. We believe these results will
      inspire the design of intervention strategies for many other multi-agent systems.

PMID- 29447222
TI  - Kinetics of PTEN-mediated PI(3,4,5)P3 hydrolysis on solid supported membranes.
AB  - Phosphatidylinositides play important roles in cellular signaling and migration.
      Phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) is an important
      phosphatidylinositide because it acts as a secondary messenger to trigger cell
      movement and proliferation. A high level of PI(3,4,5)P3 at the plasma membrane is
      known to contribute to tumorigenesis. One key enzyme that regulates PI(3,4,5)P3
      levels at the plasma membrane is phosphatase and tensin homologue deleted on
      chromosome 10 (PTEN), which dephosphorylates PI(3,4,5)P3 through hydrolysis to
      form phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). It has been reported that
      PI(4,5)P2 is involved in positive feedback in the PI(3,4,5)P3 hydrolysis by PTEN.
      However, how PI(3,4,5)P3 dephosphorylation by PTEN is regulated, is still under
      debate. How other PI(3,4,5)P3-binding proteins affect the dephosphorylation
      kinetics catalyzed by PTEN also remains unclear. Here, we develop a fluorescent
      protein biosensor approach to study how PI(3,4,5)P3 dephosphorylation is
      regulated by PTEN as well as its membrane-mediated feedback mechanisms. Our
      observation of sigmoidal kinetics of the PI(3,4,5)P3 hydrolysis reaction supports
      the notion of autocatalysis in PTEN function. We developed a kinetic model to
      describe the observed reaction kinetics, which allowed us to i) distinguish
      between membrane-recruitment and allosteric activation of PTEN by PI(4,5)P2, ii)
      account for the influence of the biosensor on the observed reaction kinetics, and
      iii) demonstrate that all of these mechanisms contribute to the kinetics of PTEN
      mediated catalysis.

PMID- 29447223
TI  - Virome and bacteriome characterization of children with pneumonia and asthma in
      Mexico City during winter seasons 2014 and 2015.
AB  - BACKGROUND: Acute asthma exacerbations and pneumonia are important causes of
      morbidity and mortality in children and may coexist in the same children,
      although symptom overlap may lead to difficulties in diagnosis. Microbial and
      viral diversity and differential abundance of either may play an important role
      in infection susceptibility and the development of acute and chronic respiratory
      diseases. OBJECTIVES: To describe the virome and bacteriome present in the upper
      respiratory tract of hospitalized children with a clinical diagnosis of asthma
      and pneumonia during an acute exacerbation and an acute respiratory illness ARI
      episode respectively. METHODS: During the winter seasons of 2013-2014 and 2014
      2015, 134 nasopharyngeal swabs samples of children <15 years of age with ARI
      hospitalized at a referral hospital for respiratory diseases were selected based
      on clinical diagnosis of asthma or pneumonia. The virome and bacteriome were
      characterized using Whole Genome Sequencing (WGS) and in-house bioinformatics
      analysis pipeline. RESULTS: The Asthma group was represented mainly by RV-C, BoV
      1 and RSV-B and the pneumonia group by Bacteriophage EJ-1 and TTMV. TTV was found
      in both groups with a similar amount of reads. About bacterial composition
      Moraxella catarrhalis, Propionibacterium acnes and Acinetobacter were present in
      asthma and Veillonella parvula and Mycoplasma pneumoniae in pneumonia.
      Streptococcus pneumoniae and Haemophilus influenzae were mostly found with both
      asthma and pneumonia. CONCLUSIONS: Our results show a complex viral and bacterial
      composition in asthma and pneumonia groups with a strong association of RV-C
      presence in asthmatic children. We observed Streptococcus pneumoniae and
      Haemophilus influenzae concurrently in both groups.

PMID- 29447224
TI  - Directional freezing for the cryopreservation of adherent mammalian cells on a
      substrate.
AB  - Successfully cryopreserving cells adhered to a substrate would facilitate the
      growth of a vital confluent cell culture after thawing while dramatically
      shortening the post-thaw culturing time. Herein we propose a controlled slow
      cooling method combining initial directional freezing followed by gradual cooling
      down to -80 degrees C for robust preservation of cell monolayers adherent to a
      substrate. Using computer controlled cryostages we examined the effect of cooling
      rates and dimethylsulfoxide (DMSO) concentration on cell survival and established
      an optimal cryopreservation protocol. Experimental results show the highest post
      thawing viability for directional ice growth at a speed of 30 MUm/sec (equivalent
      to freezing rate of 3.8 degrees C/min), followed by gradual cooling of the sample
      with decreasing rate of 0.5 degrees C/min. Efficient cryopreservation of three
      widely used epithelial cell lines: IEC-18, HeLa, and Caco-2, provides proof-of
      concept support for this new freezing protocol applied to adherent cells. This
      method is highly reproducible, significantly increases the post-thaw cell
      viability and can be readily applied for cryopreservation of cellular cultures in
      microfluidic devices.

PMID- 29447225
TI  - Low apolipoprotein A-I levels in Friedreich's ataxia and in frataxin-deficient
      cells: Implications for therapy.
AB  - Friedreich's ataxia (FA) is an autosomal recessive neurodegenerative disorder,
      which results primarily from reduced expression of the mitochondrial protein
      frataxin. FA has an estimated prevalence of one in 50,000 in the population,
      making it the most common hereditary ataxia. Paradoxically, mortality arises most
      frequently from cardiomyopathy and cardiac failure rather than from neurological
      effects. Decreased high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-l)
      levels in the general population are associated with an increased risk of
      mortality from cardiomyopathy and heart failure. However, the pathophysiology of
      heart disease in FA is non-vascular and there are conflicting data on HDL
      cholesterol in FA. Two studies have shown a decrease in HDL-cholesterol compared
      with controls and two have shown there was no difference between FA and controls.
      One also showed that there was no difference in serum Apo-A-I levels in FA when
      compared with controls. Using a highly specific stable isotope dilution mass
      spectrometry-based assay, we demonstrated a 21.6% decrease in serum ApoA-I in FA
      patients (134.8 mg/dL, n = 95) compared with non-affected controls (172.1 mg/dL,
      n = 95). This is similar to the difference in serum ApoA-I levels between non
      smokers and tobacco smokers. Knockdown of frataxin by > 70% in human hepatoma
      HepG2 cells caused a 20% reduction in secreted ApoA-I. Simvastatin, a 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor caused a 200% increase in
      HMG-CoA in the control HepG2 cells with a similar increase in the frataxin
      knockdown HepG2 cells, back to levels found in the control cells. There was a
      concomitant 20% increase in secreted ApoA-I to levels found in the control cells
      that were treated with simvastatin. This study provides compelling evidence that
      ApoA-I levels are reduced in FA patients compared with controls and suggest that
      statin treatment would normalize the ApoA-I levels.

PMID- 29447226
TI  - Barriers and facilitators to antiretroviral therapy adherence among Peruvian
      adolescents living with HIV: A qualitative study.
AB  - AIDS deaths among adolescents are increasing globally. This qualitative study
      investigated the barriers and facilitators to cART adherence among Peruvian
      adolescents living with HIV. Guided by a social ecological model, we analyzed
      transcripts from 24 psychosocial support groups for HIV-positive adolescents aged
      13-17 years and 15 individual, in-depth interviews with cART providers and
      caregivers to identify the barriers and facilitators to cART adherence at the
      individual, family/caregiver and hospital levels. Most barriers and facilitators
      to cART adherence clustered at the individual and family/caregiver levels,
      centering on support provided to adolescents; history of declining health due to
      suboptimal cART adherence; side effects from antiretroviral drugs; and cART
      misinformation. Interventions to support adolescent HIV cART adherence should
      begin at the individual and family/caregiver levels and include an educational
      component. No adolescent living with HIV should die from AIDS in an era of
      accessible cART.

PMID- 29447227
TI  - Probiotic effect of Pichia pastoris X-33 produced in parboiled rice effluent and
      YPD medium on broiler chickens.
AB  - In a previous paper we showed that the yeast Pichia pastoris X-33 grown in
      parboiled rice effluent supplemented with glycerol byproduct from the biodiesel
      industry improved the quality of the effluent. In this paper we show the
      validation of this yeast (PPE) as probiotic for broilers. Its effect on feed
      efficiency and immunomodulation was compared with the same yeast grown in yeast
      peptone dextrose medium (PPY), with Saccharomyces boulardii (SBY) and with the
      controls fed unsupplemented feed (CON). One-day-old female chicks were vaccinated
      against infectious bursal disease (IBD) and the titers of anti-IBD antibodies
      were measured by ELISA. PPE group had the highest mean titres on days 14 and 28
      (p<0,05), and at 28 days, 64% of the animals showed seroconvertion. The PPE group
      also showed the best weight gains at 42 days of age, that, on days 7, 14 and 21
      were 19%, 15%, and 8.7% higher, respectively, than the control group. The best
      feed conversion, 8.2% higher than the control group, was obtained by PPY at 42
      days. Histopathological studies did not detect any undesirable effects in the
      supplemented animals. We concluded that Pichia pastoris X-33 when grown in
      effluents of the rice parboiling industry supplemented with glycerol byproduct
      from the biodiesel has probiotic properties for poultry.

PMID- 29447228
TI  - Chromosomal distribution of pTa-535, pTa-86, pTa-713, 35S rDNA repetitive
      sequences in interspecific hexaploid hybrids of common wheat (Triticum aestivum
      L.) and spelt (Triticum spelta L.).
AB  - Fluorescent in situ hybridization (FISH) relies on fluorescent-labeled probes to
      detect specific DNA sequences in the genome, and it is widely used in cytogenetic
      analyses. The aim of this study was to determine the karyotype of T. aestivum and
      T. spelta hybrids and their parental components (three common wheat cultivars and
      five spelt breeding lines), to identify chromosomal aberrations in the evaluated
      wheat lines, and to analyze the distribution of polymorphisms of repetitive
      sequences in the examined hybrids. The FISH procedure was carried out with four
      DNA clones, pTa-86, pTa-535, pTa-713 and 35S rDNA used as probes. The observed
      polymorphisms between the investigated lines of common wheat, spelt and their
      hybrids was relatively low. However, differences were observed in the
      distribution of repetitive sequences on chromosomes 4A, 6A, 1B and 6B in selected
      hybrid genomes. The polymorphisms observed in common wheat and spelt hybrids
      carry valuable information for wheat breeders. The results of our study are also
      a valuable source of knowledge about genome organization and diversification in
      common wheat, spelt and their hybrids. The relevant information is essential for
      common wheat breeders, and it can contribute to breeding programs aimed at
      biodiversity preservation.

PMID- 29447229
TI  - HIV epidemics in Shenzhen and Chongqing, China.
AB  - OBJECTIVE: Men who have sex with men (MSM) and heterosexuals are the populations
      with the fastest growing HIV infection rates in China. We characterize the
      epidemic growth and age patterns between these two routes from 2004 to 2015 in
      Chongqing and Shenzhen, China. DESIGN AND METHODS: Data were downloaded from the
      National HIV/ AIDS Comprehensive Response Information Management System. For the
      new HIV diagnoses of heterosexuals and MSM in both cities, we estimated the
      growth rates by fitting different sub-exponential models. Heat maps are used to
      show their age patterns. We used histograms to compare these patterns by birth
      cohort. RESULTS: The MSM epidemics grew significantly in both cities. Chongqing
      experienced quadratic growth in HIV reported cases with an estimated growth rate
      of 0.086 per week and a "deceleration rate" of 0.673. HIV reported cases of MSM
      in Shenzhen grew even more drastically with a growth rate of 0.033 per week and
      "deceleration rate" of 0.794. The new infections are mainly affecting the ages of
      18 to 30 in Chongqing and ages of 20 to 35 in Shenzhen. They peaked in early
      1990's and mid-1990's birth cohorts in Chongqing and Shenzhen respectively. The
      HIV epidemic among heterosexuals grew rapidly in both cities. The growth rates
      were estimated as 0.02 and 0.028 in Chongqing and Shenzhen respectively whereas
      the "deceleration rates" were 0.878 and 0.790 in these two places. It affected
      mostly aged 18 to 75 in males and 18 to 65 in females in Chongqing and aged 18 to
      45 in males and 18 to 50 in females in Shenzhen in 2015. In Chongqing, the
      heterosexual female epidemics display two peaks in HIV diagnoses in the birth
      cohorts of early 1950's and early 1980's, with heterosexual male epidemics peaked
      in early 1940's and early 1960's. The heterosexual male and female epidemics
      display higher rates in the birth cohort 1940-1960, than the birth cohort 1960
      1990. It peaked in birth cohorts of 1950's and 1980's in Shenzhen. CONCLUSIONS:
      We revealed striking differences in epidemic growth and age patterns of the HIV
      epidemics in these two cities. Our results may be used to inform age-targeted
      public health policies to curb their epidemic growth.

PMID- 29447231
TI  - Preparedness of lower-level health facilities and the associated factors for the
      outpatient primary care of hypertension: Evidence from Tanzanian national survey.
AB  - INTRODUCTION: Sub-Saharan Africa is experiencing a rapid rise in the burden of
      non-communicable diseases in both urban and rural areas. Data on health system
      preparedness to manage hypertension and other non-communicable diseases remains
      scarce. This study aimed to assess the preparedness of lower-level health
      facilities for outpatient primary care of hypertension in Tanzania. METHODS: This
      study used data from the 2014-2015 Tanzania Service Provision Assessment survey.
      The facility was considered as prepared for the outpatient primary care of
      hypertension if reported at least half (>=50%) of the items listed from each of
      the three domains (staff training and guideline, basic diagnostic equipment, and
      basic medicines) as identified by World Health Organization-Service Availability
      and Readiness Assessment manual. Data were analyzed using Stata 14. An unadjusted
      logistic regression model was used to assess the association between outcome and
      explanatory variables. All variables with a P value < 0.2 were fitted into the
      multiple logistic regression models using a 5% significance level. RESULTS: Out
      of 725 health facilities involved in the current study, about 68% were public
      facilities and 73% located in rural settings. Only 28% of the assessed facilities
      were considered prepared for the outpatient primary care of hypertension. About
      9% and 42% of the assessed facilities reported to have at least one trained staff
      and guidelines for hypertension respectively. In multivariate analysis, private
      facilities [AOR = 2.7, 95% CI; 1.2-6.1], urban location [AOR = 2.2, 95% CI; 1.2
      4.2], health centers [AOR = 5.2, 95% CI; 3.1-8.7] and the performance of routine
      management meetings [AOR = 2.6, 95% CI; 1.1-5.9] were significantly associated
      with preparedness for the outpatient primary care of hypertension. CONCLUSION:
      The primary healthcare system in Tanzania is not adequately equipped to cope with
      the increasing burden of hypertension and other non-communicable diseases. Rural
      location, public ownership, and absence of routine management meetings were
      associated with being not prepared. There is a need to strengthen the primary
      healthcare system in Tanzania for better management of chronic diseases and curb
      their rising impact on health outcomes.

PMID- 29447230
TI  - Propofol induces a metabolic switch to glycolysis and cell death in a
      mitochondrial electron transport chain-dependent manner.
AB  - The intravenous anesthetic propofol (2,6-diisopropylphenol) has been used for the
      induction and maintenance of anesthesia and sedation in critical patient care.
      However, the rare but severe complication propofol infusion syndrome (PRIS) can
      occur, especially in patients receiving high doses of propofol for prolonged
      periods. In vivo and in vitro evidence suggests that the propofol toxicity is
      related to the impaired mitochondrial function. However, underlying molecular
      mechanisms remain unknown. Therefore, we investigated effects of propofol on cell
      metabolism and death using a series of established cell lines of various origins,
      including neurons, myocytes, and trans-mitochondrial cybrids, with defined
      mitochondrial DNA deficits. We demonstrated that supraclinical concentrations of
      propofol in not less than 50 MUM disturbed the mitochondrial function and induced
      a metabolic switch, from oxidative phosphorylation to glycolysis, by targeting
      mitochondrial complexes I, II and III. This disturbance in mitochondrial electron
      transport caused the generation of reactive oxygen species, resulting in
      apoptosis. We also found that a predisposition to mitochondrial dysfunction,
      caused by a genetic mutation or pharmacological suppression of the electron
      transport chain by biguanides such as metformin and phenformin, promoted propofol
      induced caspase activation and cell death induced by clinical relevant
      concentrations of propofol in not more than 25 MUM. With further experiments with
      appropriate in vivo model, it is possible that the processes to constitute the
      molecular basis of PRIS are identified.

PMID- 29447232
TI  - Hepatitis B virus genotypes A1, A2 and E in Cape Verde: Unequal distribution
      through the islands and association with human flows.
AB  - Hepatitis B virus (HBV) diversity has not been previously studied in Cape Verde.
      The archipelago was discovered in 1460 by Portuguese explorers, who brought
      African slaves to colonise the islands. In this study, we investigated the HBV
      characteristics from 183 HBsAg-positive Cape Verdean individuals. Phylogenetic
      analysis of the pre-S/S region and the full-length genomes revealed 54 isolates
      with HBV/A1 (57%), 21 with HBV/A2 (22%), 19 with HBV/E (20%), and one with HBV/D
      (1%). HBV genotypes and subgenotypes were unequally distributed through the
      islands. In Sao Vicente, the main northern island, most isolates (84%) belonged
      to the African-originated HBV/A1, with the remaining isolates belonging to
      HBV/A2, which is prevalent in Europe. Interestingly, the HBV/A1 isolates from Sao
      Vicente were closely related to Brazilian sequences into the Asian-American
      clade, which suggests the dissemination of common African ancestors through slave
      trade. In contrast, in Santiago and nearby southern islands, where a recent
      influx from different populations circulates, a higher diversity of HBV was
      observed: HBV/A1 (40%); HBV/E (32%); HBV/A2 (28%); and HBV/D (1%). HBV/E is a
      recent genotype disseminated in Africa that was absent in the era of the slave
      trade. African and European human flows at different times of the history may
      explain the HBV diversity in Cape Verde. The possible origin and specifics of
      each HBV genotype circulating in Cape Verde are discussed.

PMID- 29447233
TI  - Notch signaling inhibitor DAPT provides protection against acute craniocerebral
      injury.
AB  - Notch signaling pathway is involved in many physiological and pathological
      processes. The gamma-secretase inhibitor DAPT inhibits Notch signaling pathway
      and promotes nerve regeneration after cerebral ischemia. However, neuroprotective
      effects of DAPT against acute craniocerebral injury remain unclear. In this
      study, we established rat model of acute craniocerebral injury, and found that
      with the increase of damage grade, the expression of Notch and downstream protein
      Hes1 and Hes5 expression gradually increased. After the administration of DAPT,
      the expression of Notch, Hes1 and Hes5 was inhibited, apoptosis and oxidative
      stress decreased, neurological function and cognitive function improved. These
      results suggest that Notch signaling can be used as an indicator to assess the
      severity of post-traumatic brain injury. Notch inhibitor DAPT can reduce
      oxidative stress and apoptosis after acute craniocerebral injury, and is a
      potential drug for the treatment of acute craniocerebral injury.

PMID- 29447235
TI  - The dominance of introspective measures and what this implies: The example of
      environmental attitude.
AB  - The behavioral sciences, including most of psychology, seek to explain and
      predict behavior with the help of theories and models that involve concepts
      (e.g., attitudes) that are subsequently translated into measures. Currently, some
      subdisciplines such as social psychology focus almost exclusively on measures
      that demand reflection or even introspection when administered to persons. We
      argue that such a focus hinders progress in explaining behavior. One major reason
      is that such an exclusive focus on reflections results in common method bias,
      which then produces spurious relations, or in other words, low discriminant
      validity. Without the valid measurement of theoretical concepts, theoretical
      assumptions cannot be tested, and hence, theory development will be hampered. We
      argue that the use of a greater variety of methods would reduce these problems
      and would in turn foster theory building. Using a representative sample of N =
      472 participants (age: M = 51.0, SD = 17.7; 54% female), we compared the validity
      of a classical introspective attitude measure (i.e., the New Ecological Paradigm)
      with that of an alternative attitude measure (i.e., the General Ecological
      Behavior scale). The latter measure, which was based on self-reported behavior,
      showed substantially better validity that we argue could aid theory development.

PMID- 29447234
TI  - Folic acid derived-P5779 mimetics regulate DAMP-mediated inflammation through
      disruption of HMGB1:TLR4:MD-2 axes.
AB  - High mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP)
      protein that mediates inflammatory responses after infection or injury.
      Previously, we reported a peptide inhibitor of HMGB1 (P5779) that acts by
      directly interrupting HMGB1/MD-2 binding. Here, fingerprint similarity search and
      docking studies suggest folic acid derived-drugs function as P5779 mimetopes.
      Molecular dynamic (MD) simulation studies demonstrate that folic acid mimics the
      binding of P5779 at the TLR4 and MD-2 intersection. In surface plasmon resonance
      (SPR) studies, these drugs showed direct binding to TLR4/MD-2 but not HMGB1.
      Furthermore, these P5779 mimetopes inhibit HMGB1 and MD-2 binding and suppress
      HMGB1-induced TNF release in human macrophages in the nanomolar range. We assert
      from our findings that their demonstrated anti-inflammatory effects may be
      working through TLR4-dependent signaling.

PMID- 29447236
TI  - The influence of a change in the meniscus cross-sectional shape on the medio
      lateral translation of the knee joint and meniscal extrusion.
AB  - OBJECTIVE: The purpose of this study was to evaluate the influence of a change in
      the meniscus cross sectional shape on its position and on the biomechanics of a
      knee joint. METHODS: One main finite element model of a left knee joint was
      created on the basis of MRI images. The model consisted of bones, articular
      cartilages, menisci and ligaments. Eight variants of this model with an increased
      or decreased meniscus height were then prepared. Nonlinear static analyses with a
      fixed flexion/extension movement for a compressive load of 1000 N were performed.
      The additional analyses for those models with a constrained medio-lateral
      relative bone translation allowed for an evaluation of the influence of this
      translation on a meniscus external shift. RESULTS: It was observed that a
      decrease in the meniscus height caused a decrease in the contact area, together
      with a decrease in the contact force between the flattened meniscus and the
      cartilage. For the models with an increased meniscus height, a maximal value of
      force acting on the meniscus in a medio-lateral direction was obtained. The
      results have shown that the meniscus external shift was approximately
      proportional to the meniscus slope angle, but that relationship was modified by a
      medio-lateral relative bone translation. It was found that the translation of the
      femur relative to the tibia may be dependent on the geometry of the menisci.
      CONCLUSIONS: The results have suggested that a change in the meniscus geometry in
      the cross sectional plane can considerably affect not only the meniscal external
      shift, but also the medio-lateral translation of the knee joint as well as the
      congruency of the knee joint.

PMID- 29447238
TI  - Ex situ cultivation protocol for Cystoseira amentacea var. stricta (Fucales,
      Phaeophyceae) from a restoration perspective.
AB  - Due to multiple impacts, Cystoseira forests are experiencing a significant
      decline, which is affecting the ecosystem services they provide. Despite
      conservation efforts, there is an urgent need to develop best practices and large
      scale restoration strategies. To implement restoration actions, we developed an
      ex situ protocol for the cultivation of Cystoseira. amentacea var. stricta, aimed
      at reducing the time needed for laboratory culture, thus avoiding prolonged
      maintenance and minimizing costs. Specifically, we tested the effects of
      temperature, light and substratum on settlement and growth of early life stages
      using a factorial experiment. Temperature (20 and 24 degrees C) and photoperiod
      (15L:9D) were selected to reflect the conditions experienced in the field during
      the reproductive period. Two light intensities (125 and 250 MUmol photons m-2s-1)
      were selected to mimic the condition experienced in the absence of canopy (i.e.
      barren-higher light intensity) or in the understory (lower light intensity)
      during gamete release. The tested substrata were flat polished pebbles and rough
      clay tiles. The release of gametes and the successive survival and development of
      embryo and germlings were followed for two weeks. Regardless of the culture
      conditions, rougher tiles showed higher zygote settlement, but the substrata did
      not affect the successive development. Zygote mortality after one week averaged
      50% and at the end of the second week, embryonic survival was higher under lower
      light and temperature conditions, which also determined the growth of larger
      embryos.

PMID- 29447237
TI  - Pathophysiological and neurobehavioral characteristics of a propionic acid
      mediated autism-like rat model.
AB  - Autism spectrum disorder (ASD) is induced by complex hereditary and environmental
      factors. However, the mechanisms of ASD development are poorly understood. The
      purpose of this study was to identify standard indicators of this condition by
      comparing clinical, pathophysiological, and neurobehavioral features in an autism
      like animal model. A total of 22 male Sprague-Dawley rats were randomly divided
      into control and 500 mg/kg propionic acid (PPA)-treated groups. Rats were
      subjected to behavioral tests, gene expression analyses, and histological
      analyses to detect pathophysiological and neurobehavioral alterations.
      Exploratory activity and non-aggressive behavior were significantly reduced in
      PPA-treated rats, whereas enhanced aggressive behavior during adjacent
      interactions was observed on day 14 after PPA administration. To evaluate gene
      expression after PPA administration, we analyzed hippocampal tissue using reverse
      transcription PCR. Glial fibrillary acidic protein was augmented in the PPA
      treated group on day 14 after appearance of ASD-like behaviors by PPA
      administration, whereas octamer-binding transcription factor 4 expression was
      significantly decreased in the PPA-treated group. Histological evaluation
      revealed significantly reduced diameter and layer thickness of granule cells in
      PPA-treated rats compared with control rats. We conclude that PPA administration
      induced abnormal neural cell organization, which may have led to autism-like
      neurobehaviors, including increased aggressive behavior, reduced exploratory
      activity, and isolative and passive behaviors.

PMID- 29447239
TI  - Coaxial technique-promoted diagnostic accuracy of CT-guided percutaneous cutting
      needle biopsy for small and deep lung lesions.
AB  - Coaxial technique is extensively applied to facilitate percutaneous lung lesion
      biopsy. However, the impact of coaxial technique on diagnostic accuracy remains
      undecided. We reviewed 485 patients who underwent percutaneous CT-guided needle
      biopsies of lung lesions in our hospital. All of these biopsies were performed
      using either a cutting needle alone (n = 268) or a cutting needle combined with a
      coaxial needle (n = 217). The diagnostic accuracy and complications resulting
      from the two techniques were then compared. The diagnostic accuracies of the two
      techniques were comparably high, at 98.2% (with coaxial technique) and 95.9%
      (without coaxial technique), p = 0.24. Subgroup analysis discovered that for
      patients with lesions measuring < 1.5 cm and needle path length >= 4 cm, the
      coaxial technique achieved a higher diagnostic accuracy (95.5% vs. 72.7%, p =
      0.023). The biopsy was well tolerated in all of the patients. Pneumothorax
      occurred less often in patients who were biopsied with the coaxial technique (19
      versus 43, p = 0.024). Thus, the application of the coaxial technique could
      improve diagnostic accuracy in patients with small and deep lung lesions, and
      could reduce the risk of pneumothorax. The combined use of cutting needles with
      coaxial needles is the preferred technique for performing percutaneous CT-guided
      lung biopsies.

PMID- 29447240
TI  - B cell subset distribution is altered in patients with severe periodontitis.
AB  - Several studies have recently highlighted the implication of B cells in
      physiopathogenesis of periodontal disease by showing that a B cell deficiency
      leads to improved periodontal parameters. However, the detailed profiles of
      circulating B cell subsets have not yet been investigated in patients with severe
      periodontitis (SP). We hypothesised that an abnormal distribution of B cell
      subsets could be detected in the blood of patients with severe periodontal
      lesions, as already reported for patients with chronic inflammatory diseases as
      systemic autoimmune diseases. Fifteen subjects with SP and 13 subjects without
      periodontitis, according to the definition proposed by the CDC periodontal
      disease surveillance work group, were enrolled in this pilot observational study.
      Two flow cytometry panels were designed to analyse the circulating B and B1 cell
      subset distribution in association with the RANKL expression. A significantly
      higher percentage of CD27+ memory B cells was observed in patients with SP. Among
      these CD27+ B cells, the proportion of the switched memory subset was
      significantly higher. At the same time, human B1 cells, which were previously
      associated with a regulatory function (CD20+CD69-CD43+CD27+CD11b+), decreased in
      SP patients. The RANKL expression increased in every B cell subset from the SP
      patients and was significantly greater in activated B cells than in the subjects
      without periodontitis. These preliminary results demonstrate the altered
      distribution of B cells in the context of severe periodontitis. Further
      investigations with a larger cohort of patients can elucidate if the analysis of
      the B cell compartment distribution can reflect the periodontal disease activity
      and be a reliable marker for its prognosis (clinical trial registration number:
      NCT02833285, B cell functions in periodontitis).

PMID- 29447241
TI  - Selective targeting of tumor associated macrophages in different tumor models.
AB  - Tumor progression largely depends on the presence of alternatively polarized (M2)
      tumor-associated macrophages (TAMs), whereas the classical M1-polarized
      macrophages can promote anti-tumorigenic immune responses. Thus, selective
      inhibition of M2-TAMs is a desirable anti-cancer approach in highly resistant
      tumor entities such as hepatocellular carcinoma (HCC) or breast cancer. We here
      examined whether a peptide that selectively binds to and is internalized by in
      vitro-differentiated murine M2 macrophages as compared to M1 macrophages, termed
      M2pep, could be used to selectively target TAMs in HCC and breast carcinoma. We
      confirmed selectivity of M2pep for in vitro M2 polarized macrophages. Upon
      incubation of suspended mixed 4T1 tumor cells with M2pep, high amounts of the
      TAMs were found to be associated with M2pep, whereas in mixed tumor cell
      suspensions from two HCC mouse models, M2pep showed only low-degree binding to
      TAMs. M2pep also showed low-degree targeting of liver macrophages. This indicates
      that the TAMs in different tumor entities show different targeting of M2pep and
      that M2pep is a very promising approach to develop selective M2-TAM-targeting in
      tumor entities containing M2-TAMs with significant amounts of the so far elusive
      M2pep receptor(s).

PMID- 29447242
TI  - A novel ligand on astrocytes interacts with natural cytotoxicity receptor NKp44
      regulating immune response mediated by NK cells.
AB  - NK cells play important role in immunity against pathogens and cancer. NK cell
      functions are regulated by inhibitory and activating receptors binding
      corresponding ligands on the surface of target cells. NK cells were shown to be
      recruited to the CNS following several pathological conditions. NK cells could
      impact CNS physiology by killing glial cells and by secreting IFN-gamma.
      Astrocytes are intimately involved in immunological and inflammatory events
      occurring in the CNS and reactive astrogliosis is a key feature in HIV-associated
      neurocognitive disorders. There is little data on NK-astrocyte interactions and
      ligands expressed on astrocytes that could impact NK cell function. Natural
      cytotoxicity receptors (NCRs) play a critical role in the cytolytic function of
      NK cells. Among the NCRs, NKp44 is unique in expression and signal transduction.
      NKp44 is expressed only upon activation of NK cells and it can mediate both
      activating and inhibitory signals to NK cells. Here, we have studied the
      expression and function of natural cytotoxicity receptor NKp44 upon NK-astrocytes
      interactions in the presence or absence of an HIV peptide (HIV-3S peptide) shown
      to induce NK cell killing of CD4+ T cells during HIV-infection. Using a fusion
      protein consisting of the extracellular domain of NKp44 fused to Fc portion of
      human IgG, we determined the expression of a novel ligand for NKp44 (NKp44L) on
      astrocytes. Incubation of astrocytes with HIV-3S peptide downregulated NKp44L
      expression on astrocytes implicating protection from NK mediated killing. Thus,
      our study showed that NKp44 have a protective effect on astrocytes from NK cell
      mediated killing during HIV infection and impact astrocyte role in HAND.

PMID- 29447243
TI  - Differences in the intestinal microbiota between uninfected piglets and piglets
      infected with porcine epidemic diarrhea virus.
AB  - Porcine epidemic diarrhea, a disastrous gastrointestinal disease, causes great
      financial losses due to its high infectivity, morbidity and mortality in suckling
      piglets despite the development and application of various vaccines. In this
      study, high-throughput sequencing was used to explore differences in the
      intestinal microbiota between uninfected piglets and piglets infected with
      porcine epidemic diarrhea virus (PEDV). The results revealed that the small
      intestinal microbiota of suckling piglets infected with PEDV showed low diversity
      and was dominated by Proteobacteria (49.1%). Additionally, the composition of the
      small intestinal microbiota of sucking piglets infected with PEDV showed marked
      differences from that of the uninfected piglets. Some of the taxa showing
      differences in abundance between uninfected piglets and piglets infected with
      PEDV were associated with cellular transport and catabolism, energy metabolism,
      the biosynthesis of other secondary metabolites, and amino acid metabolism as
      determined through the prediction of microbial function based on the bacterial
      16S rRNA gene. Therefore, adjusting the intestinal microbiota might be a
      promising method for the prevention or treatment of PEDV.

PMID- 29447244
TI  - Influence of hiatal hernia and male sex on the relationship between alcohol
      intake and occurrence of Barrett's esophagus.
AB  - BACKGROUND: The association of alcohol intake with the incidence of Barrett's
      esophagus (BE) has been inconsistent. Although hiatal hernia and male sex are
      well-known risk factors of BE, its effect on the association of alcohol intake
      with the incidence of BE remains unknown. AIM: To investigate whether the
      influence of alcohol intake on the occurrence of BE might differ depending on
      male sex and presence of hiatal hernia. METHODS: We utilized a database of 8031
      patients that underwent upper endoscopy for health screening in a prospective,
      multicenter, cohort study (the Upper Gastro Intestinal Disease study). The
      incidence of endoscopic columnar-lined esophagus (eCLE; endoscopically diagnosed
      BE) was the outcome variable. Multivariable logistic regression analysis was
      conducted to assess the association between alcohol intake and eCLE stratified by
      male sex and hiatal hernia, adjusting for clinical features and other potential
      confounders. RESULTS: Alcohol intake (>=20 g/day) showed a marginally significant
      association with the incidence of eCLE in participants without hiatal hernia (0
      vs. >=20 g/day; odds ratio [OR], 1.62; 95% confidence interval [CI], 0.92-2.85, P
      = 0.09) but not in participants with hiatal hernia (0 vs. >=20/day; OR, 0.99; 95%
      CI, 0.59-1.65; P = 0.95). Furthermore, alcohol intake (>=20 g/day) was
      significantly associated with the incidence of eCLE in male participants without
      hiatal hernia (0 vs. >=20 g/day; OR, 1.98; 95% CI, 1.04-4.03; P = 0.04) but not
      in female participants without hiatal hernia (0 vs. >=20 g/day; OR, 0.47; 95% CI,
      0.03-2.37; P = 0.42). CONCLUSIONS: The effect of alcohol intake on the incidence
      of eCLE might be associated with hiatal hernia status and male sex.

PMID- 29447245
TI  - Adverse obstetric outcomes during delivery hospitalizations complicated by
      suicidal behavior among US pregnant women.
AB  - OBJECTIVE: The effects of suicidal behavior on obstetric outcomes remain
      dangerously unquantified. We sought to report on the risk of adverse obstetric
      outcomes for US women with suicidal behavior at the time of delivery. METHODS: We
      performed a cross-sectional analysis of delivery hospitalizations from 2007-2012
      National (Nationwide) Inpatient Sample. From the same hospitalization record,
      International Classification of Diseases codes were used to identify suicidal
      behavior and adverse obstetric outcomes. Adjusted odds ratios (aOR) and 95%
      confidence intervals (CI) were obtained using logistic regression. RESULTS: Of
      the 23,507,597 delivery hospitalizations, 2,180 were complicated by suicidal
      behavior. Women with suicidal behavior were at a heightened risk for outcomes
      including antepartum hemorrhage (aOR = 2.34; 95% CI: 1.47-3.74), placental
      abruption (aOR = 2.07; 95% CI: 1.17-3.66), postpartum hemorrhage (aOR = 2.33; 95%
      CI: 1.61-3.37), premature delivery (aOR = 3.08; 95% CI: 2.43-3.90), stillbirth
      (aOR = 10.73; 95% CI: 7.41-15.56), poor fetal growth (aOR = 1.70; 95% CI: 1.10
      2.62), and fetal anomalies (aOR = 3.72; 95% CI: 2.57-5.40). No significant
      association was observed for maternal suicidal behavior with cesarean delivery,
      induction of labor, premature rupture of membranes, excessive fetal growth, and
      fetal distress. The mean length of stay was longer for women with suicidal
      behavior. CONCLUSION: During delivery hospitalization, women with suicidal
      behavior are at increased risk for many adverse obstetric outcomes, highlighting
      the importance of screening for and providing appropriate clinical care for women
      with suicidal behavior during pregnancy.

PMID- 29447246
TI  - Fried food intake and risk of nonfatal acute myocardial infarction in the Costa
      Rica Heart Study.
AB  - Economic development in middle-income countries has led to a noticeable rise in
      the availability of commercial deep fried foods and lifestyles that require
      eating meals "on the go" and outside of the home. Yet, data from these countries
      where fried foods were traditionally prepared at home are scarce, despite several
      studies showing the potential adverse effects of fried food consumption on risk
      for heart disease. We aimed to examine whether consumption of fried foods inside
      or outside of the home is associated with an increased risk of myocardial
      infarction (MI) among Hispanic/Latinos living in Costa Rica. Participants were
      incident cases of a first acute MI (n = 2,154) and randomly selected controls
      matched for age, sex, and residence (n = 2,154). After adjustment for traditional
      cardiovascular risk factors, including history of diabetes, history of
      hypertension, smoking, abdominal obesity, income, educational years, occupation,
      alcohol intake, dietary intakes of saturated fatty acid, fiber intake, and total
      energy intake, the multivariable-adjusted odds ratio (OR, 95% CI) for risk of MI
      were 1.00 (reference), 1.02 (0.86-1.21), 1.26 (0.81-1.95), and 1.58 (1.08-2.30)
      for intake of fried foods outside of the home <1/week, 1-3/week, 4-6/week, and
      1/day, respectively (P trend = 0.02); and 1.00, 0.81 (0.65-1.00), 0.81 (0.61
      1.09), and 0.93 (0.72-1.19), respectively (P for trend = 0.65) for intake of
      fried foods inside the home. The data suggest that consumption of fried foods
      outside of the home, a practice that has been associated with economic
      development, could have adverse effects on cardiovascular disease.

PMID- 29447247
TI  - Differences between fellow eyes of acute and chronic primary angle closure
      (glaucoma): An ultrasound biomicroscopy quantitative study.
AB  - PURPOSE: To compare various biometric parameters between fellow eyes of acute
      primary angle closure (glaucoma) [APAC(G)] and fellow eyes of chronic primary
      angle closure (glaucoma) [CPAC(G)]. METHODS: Ultrasound biomicroscopy
      examinations were performed on 47 patients with unilateral APAC(G) and 41
      patients with asymmetric CPAC(G) before laser peripheral iridotomy and
      pilocarpine treatment. Anterior chamber depth and width (ACD and ACW), lens vault
      (LV), iris curvature (IC), iris root distance (IRD), trabecular-ciliary process
      distance (TCPD), iris-ciliary process distance (ICPD), trabecular-ciliary angle
      (TCA), and other biometric parameters were compared between fellow eyes of
      APAC(G) and fellow eyes of CAPC(G). RESULTS: Compared with fellow eyes of
      CPAC(G), fellow eyes of APAC(G) had smaller ACD (P < 0.001), ACW (P = 0.007),
      TCPD (P = 0.016), ICPD (P = 0.008), and TCA (P = 0.006), as well as larger LV (P
      = 0.002), IC (P = 0.012), and IRD (P = 0.003). On multivariate logistic
      regression analyses, a 0.1 mm decrease in ACD (odds ratio [OR]: 0.705, 95%CI:
      0.564-0.880, P = 0.002), ICPD (OR: 0.557, 95%CI: 0.335-0.925, P = 0.024), and a
      0.1 mm increase in IRD (OR: 2.707, 95%CI: 1.025-7.149, P = 0.045), was
      significantly associated with occurrence of acute angle closures. CONCLUSIONS:
      Fellow eyes of APAC(G) had smaller anterior segment dimensions, higher LV, more
      posterior iris insertion, greater IC, and more anteriorly rotated ciliary body
      compared with fellow eyes of CPAC(G). ACD, ICPD, and IRD were the three most
      important parameters that distinguish eyes predisposed to APAC(G) or CPAC(G).

PMID- 29447248
TI  - Effect of park prescriptions with and without group visits to parks on stress
      reduction in low-income parents: SHINE randomized trial.
AB  - INTRODUCTION: Exposure to nature may reduce stress in low-income parents. This
      prospective randomized trial compares the effect of a physician's counseling
      about nature with or without facilitated group outings on stress and other
      outcomes among low-income parents. MATERIALS AND METHODS: Parents of patients
      aged 4-18 years at a clinic serving low-income families were randomized to a
      supported park prescription versus independent park prescription in a 2:1 ratio.
      Parents in both groups received physician counseling about nature, maps of local
      parks, a journal, and pedometer. The supported group received additional phone
      and text reminders to attend three weekly family nature outings with free
      transportation, food, and programming. Outcomes measured in parents at baseline,
      one month and three months post-enrollment included: stress (using the 40-point
      Perceived Stress Scale [PSS10]); park visits per week (self-report and
      journaling); loneliness (modified UCLA-Loneliness Scale); physical activity (self
      report, journaling, pedometry); physiologic stress (salivary cortisol); and
      nature affinity (validated scale). RESULTS: We enrolled 78 parents, 50 in the
      supported and 28 in the independent group. One-month follow-up was available for
      60 (77%) participants and three-month follow up for 65 (83%). Overall stress
      decreased by 1.71 points (95% CI, -3.15, -0.26). The improvement in stress did
      not differ significantly by group assignment, although the independent group had
      more park visits per week (mean difference 1.75; 95% CI [0.46, 3.04], p =
      0.0085). In multivariable analysis, each unit increase in park visits per week
      was associated with a significant and incremental decrease in stress (change in
      PSS10-0.53; 95% CI [-0.89, -0.16]; p = 0.005) at three months. CONCLUSION: While
      we were unable to demonstrate the additional benefit of group park visits, we
      observed an overall decrease in parental stress both overall and as a function of
      numbers of park visits per week. Paradoxically the park prescription without
      group park visits led to a greater increase in weekly park visits than the group
      visits. To understand the benefits of this intervention, larger trials are
      needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02623855.

PMID- 29447250
TI  - Correction: STING expression and response to treatment with STING ligands in
      premalignant and malignant disease.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187532.].

PMID- 29447249
TI  - A paralogous pair of mammalian host restriction factors form a critical host
      barrier against poxvirus infection.
AB  - Host restriction factors constitute a formidable barrier for viral replication to
      which many viruses have evolved counter-measures. Human SAMD9, a tumor suppressor
      and a restriction factor for poxviruses in cell lines, is antagonized by two
      classes of poxvirus proteins, represented by vaccinia virus (VACV) K1 and C7. A
      paralog of SAMD9, SAMD9L, is also encoded by some mammals, while only one of two
      paralogs is retained by others. Here, we show that SAMD9L functions similarly to
      SAMD9 as a restriction factor and that the two paralogs form a critical host
      barrier that poxviruses must overcome to establish infection. In mice, which
      naturally lack SAMD9, overcoming SAMD9L restriction with viral inhibitors is
      essential for poxvirus replication and pathogenesis. While a VACV deleted of both
      K1 and C7 (vK1L-C7L-) was restricted by mouse cells and highly attenuated in
      mice, its replication and virulence were completely restored in SAMD9L-/- mice.
      In humans, both SAMD9 and SAMD9L are poxvirus restriction factors, although the
      latter requires interferon induction in many cell types. While knockout of SAMD9
      with Crispr-Cas9 was sufficient for abolishing the restriction for vK1L-C7L- in
      many human cells, knockout of both paralogs was required for abolishing the
      restriction in interferon-treated cells. Both paralogs are antagonized by VACV
      K1, C7 and C7 homologs from diverse mammalian poxviruses, but mouse SAMD9L is
      resistant to the C7 homolog encoded by a group of poxviruses with a narrow host
      range in ruminants, indicating that host species-specific difference in
      SAMD9/SAMD9L genes serves as a barrier for cross-species poxvirus transmission.

PMID- 29447251
TI  - Attention to fat- and thin-related words in body-satisfied and body-dissatisfied
      women before and after thin model priming.
AB  - Understanding the cognitive processes underlying body dissatisfaction provides
      important information on the development and perpetuation of eating pathology.
      Previous research suggests that body-dissatisfied women process weight-related
      information differently than body-satisfied women, but the precise nature of
      these processing differences is not yet understood. In this study, eye-gaze
      tracking was used to measure attention to weight-related words in body
      dissatisfied (n = 40) and body-satisfied (n = 38) women, before and after
      exposure to images of thin fashion models. Participants viewed 8-second displays
      containing fat-related, thin-related, and neutral words while their eye fixations
      were tracked and recorded. Based on previous research and theory, we predicted
      that body-dissatisfied women would attend to fat-related words more than body
      satisfied women and would attend to thin-related words less. It was also
      predicted that exposure to thin model images would increase self-rated body
      dissatisfaction and heighten group differences in attention. The results
      indicated that body-dissatisfied women attended to both fat- and thin-related
      words more than body-satisfied women and that exposure to thin models did not
      increase this effect. Implications for cognitive models of eating disorders are
      discussed.

PMID- 29447252
TI  - Low-back electromyography (EMG) data-driven load classification for dynamic
      lifting tasks.
AB  - OBJECTIVE: Numerous devices have been designed to support the back during lifting
      tasks. To improve the utility of such devices, this research explores the use of
      preparatory muscle activity to classify muscle loading and initiate appropriate
      device activation. The goal of this study was to determine the earliest time
      window that enabled accurate load classification during a dynamic lifting task.
      METHODS: Nine subjects performed thirty symmetrical lifts, split evenly across
      three weight conditions (no-weight, 10-lbs and 24-lbs), while low-back muscle
      activity data was collected. Seven descriptive statistics features were extracted
      from 100 ms windows of data. A multinomial logistic regression (MLR) classifier
      was trained and tested, employing leave-one subject out cross-validation, to
      classify lifted load values. Dimensionality reduction was achieved through
      feature cross-correlation analysis and greedy feedforward selection. The time of
      full load support by the subject was defined as load-onset. RESULTS: Regions of
      highest average classification accuracy started at 200 ms before until 200 ms
      after load-onset with average accuracies ranging from 80% (+/-10%) to 81% (+/
      7%). The average recall for each class ranged from 69-92%. CONCLUSION: These
      inter-subject classification results indicate that preparatory muscle activity
      can be leveraged to identify the intent to lift a weight up to 100 ms prior to
      load-onset. The high accuracies shown indicate the potential to utilize intent
      classification for assistive device applications. SIGNIFICANCE: Active assistive
      devices, e.g. exoskeletons, could prevent back injury by off-loading low-back
      muscles. Early intent classification allows more time for actuators to respond
      and integrate seamlessly with the user.

PMID- 29447253
TI  - Combined impairments in vision, hearing and cognition are associated with greater
      levels of functional and communication difficulties than cognitive impairment
      alone: Analysis of interRAI data for home care and long-term care recipients in
      Ontario.
AB  - OBJECTIVES: The objective of the current study was to understand the added
      effects of having a sensory impairment (vision and/or hearing impairment) in
      combination with cognitive impairment with respect to health-related outcomes
      among older adults (65+ years old) receiving home care or residing in a long-term
      care (LTC) facility in Ontario, Canada. METHODS: Cross-sectional analyses were
      conducted using existing data collected with one of two interRAI assessments, one
      for home care (n = 291,824) and one for LTC (n = 110,578). Items in the
      assessments were used to identify clients with single sensory impairments (e.g.,
      vision only [VI], hearing only [HI]), dual sensory impairment (DSI; i.e., vision
      and hearing) and those with cognitive impairment (CI). We defined seven mutually
      exclusive groups based on the presence of single or combined impairments.
      RESULTS: The rate of people having all three impairments (i.e., CI+DSI) was 21.3%
      in home care and 29.2% in LTC. Across the seven groups, individuals with all
      three impairments were the most likely to report loneliness, to have a reduction
      in social engagement, and to experience reduced independence in their activities
      of daily living (ADLs) and instrumental ADLs (IADLs). Communication challenges
      were highly prevalent in this group, at 38.0% in home care and 49.2% in LTC. In
      both care settings, communication difficulties were more common in the CI+DSI
      group versus the CI-alone group. CONCLUSIONS: The presence of combined sensory
      and cognitive impairments is high among older adults in these two care settings
      and having all three impairments is associated with higher rates of negative
      outcomes than the rates for those having CI alone. There is a rising imperative
      for all health care professionals to recognize the potential presence of hearing,
      vision and cognitive impairments in those for whom they provide care, to ensure
      that basic screening occurs and to use those results to inform care plans.

PMID- 29447254
TI  - Loop diuretics are associated with greater risk of sarcopenia in patients with
      non-dialysis-dependent chronic kidney disease.
AB  - INTRODUCTION: Sarcopenia, the age-related loss of muscle mass and function,
      frequently accompanies chronic kidney disease. The aim of this study was to
      clarify the prevalence and the risk factors for sarcopenia among patients with
      non-dialysis-dependent chronic kidney disease (NDD-CKD), focusing on the use of
      drugs. METHODS: We conducted a cross-sectional analysis on a cohort of 260
      patients with NDD-CKD in a university hospital, recruited between June 2016 and
      March 2017. We extracted data on patient gender, age, cause of chronic kidney
      disease, use of drugs, and comorbidities that could potentially affect the
      prevalence of sarcopenia. Sarcopenia was diagnosed using the criteria of the
      Asian Working Group for Sarcopenia. Logistic regression analysis was performed to
      analyze the association of each factor on the prevalence of sarcopenia. RESULTS:
      25.0% of our study subjects had sarcopenia. Multivariable analysis revealed that
      an increased risk of sarcopenia was significantly associated with age, male
      gender, body mass index, diabetes mellitus, and loop diuretic use (odds ratio,
      4.59: 95% confidence interval, 1.81-11.61: P-value 0.001). CONCLUSIONS: In our
      cohort, the prevalence of sarcopenia in patients with NDD-CKD was high, and
      diuretics use, particularly loop diuretic use, was suggested to be a risk factor
      of sarcopenia. Although loop diuretics are commonly used in patients with CKD,
      careful consideration of the risk of sarcopenia may be necessary.

PMID- 29447255
TI  - Hydroxyethyl starch for volume expansion after subarachnoid haemorrhage and renal
      function: Results of a retrospective analysis.
AB  - BACKGROUND: Hydroxyethyl starch (HES) was part of "triple-H" therapy for
      prophylaxis and therapy of vasospasm in patients with subarachnoid haemorrhage
      (SAH). The European Medicines Agency restricted the use of HES in 2013 due to an
      increase of renal failure in critically ill patients receiving HES compared to
      crystalloid fluids. The occurrence of renal insufficiency in patients with SAH
      due to HES is still uncertain. The purpose of our study was to evaluate whether
      there was an association with renal impairment in patients receiving HES after
      subarachnoid haemorrhage. METHODS: Medical records of all non-traumatic SAH
      patients treated at the Departments of Anaesthesiology and Neurosurgery,
      University Hospital of Leipzig, Germany, between January 2009 and December 2014
      were analysed. Patients received either HES 6% and/or 10% (HES group, n = 183) or
      exclusively crystalloids for fluid therapy (Crystalloid group, n = 93). Primary
      outcome was the incidence of acute kidney injury. RESULTS: The study groups had
      similar characteristics except for initial SAPS scores, incidence of vasospasm
      and ICU length of stay. Patients receiving HES fulfilled significantly more often
      SIRS (systemic inflammatory response syndrome) criteria. 24.6% (45/183) of the
      patients in the HES group had acute kidney injury (KDIGO 1-3) at any time during
      their ICU stay compared to 26.9% (25/93) in the crystalloid group (p = 0.679).
      Only few patients needed renal replacement therapy with no significant difference
      between groups (Crystalloid group: 4.3%; HES group: 2.2%; p = 0.322). The
      incidence of vasospasm was increased in the HES group when compared to the
      crystalloid group (33.9% vs. 17.2%; p = 0.004). CONCLUSION: In the presented
      series of patients with non-traumatic SAH we found no significant association
      between HES therapy and the incidence of acute kidney injury. Treatment without
      HES did not worsen patient outcome.

PMID- 29447256
TI  - Modulation of neural circuits underlying temporal production by facial
      expressions of pain.
AB  - According to the Scalar Expectancy Theory, humans are equipped with a biological
      internal clock, possibly modulated by attention and arousal. Both emotions and
      pain are arousing and can absorb attentional resources, thus causing distortions
      of temporal perception. The aims of the present single-event fMRI study were to
      investigate: a) whether observation of facial expressions of pain interferes with
      time production; and b) the neural network subserving this kind of temporal
      distortions. Thirty healthy volunteers took part in the study. Subjects were
      asked to perform a temporal production task and a concurrent gender
      discrimination task, while viewing faces of unknown people with either pain
      related or neutral expressions. Behavioural data showed temporal underestimation
      (i.e., longer produced intervals) during implicit pain expression processing;
      this was accompanied by increased activity of right middle temporal gyrus, a
      region known to be active during the perception of emotional and painful faces.
      Psycho-Physiological Interaction analyses showed that: 1) the activity of middle
      temporal gyrus was positively related to that of areas previously reported to
      play a role in timing: left primary motor cortex, middle cingulate cortex,
      supplementary motor area, right anterior insula, inferior frontal gyrus,
      bilateral cerebellum and basal ganglia; 2) the functional connectivity of
      supplementary motor area with several frontal regions, anterior cingulate cortex
      and right angular gyrus was correlated to the produced interval during painful
      expression processing. Our data support the hypothesis that observing emotional
      expressions distorts subjective time perception through the interaction of the
      neural network subserving processing of facial expressions with the brain network
      involved in timing. Within this frame, middle temporal gyrus appears to be the
      key region of the interplay between the two neural systems.

PMID- 29447257
TI  - Access to health insurance coverage among sub-Saharan African migrants living in
      France: Results of the ANRS-PARCOURS study.
AB  - BACKGROUND: Migrants' access to care depends on their health insurance coverage
      in the host country. We aimed to evaluate in France the dynamic and the
      determinants of health insurance coverage acquisition among sub-Saharan migrants.
      METHODS: In the PARCOURS life-event retrospective survey conducted in 2012-2013
      in health-care facilities in the Paris region, data on health insurance coverage
      (HIC) each year since arrival in France has been collected among three groups of
      sub-Saharan migrants recruited in primary care centres (N = 763), centres for HIV
      care (N = 923) and for chronic hepatitis B care (N = 778). Year to year, the
      determinants of the acquisition and lapse of HIC were analysed with mixed-effects
      logistic regression models. RESULTS: In the year of arrival, 63.4% of women and
      55.3% of men obtained HIC. But three years after arrival, still 14% of women and
      19% of men had not obtained HIC. HIC acquisition was accelerated in case of HIV
      or hepatitis B infection, for migrants arrived after 2000, and for women in case
      of pregnancy and when they were studying. Conversely, it was slowed down in case
      of lack of a residency permit and lack of financial resources for men. In
      addition, women and men without residency permits were more likely to have lost
      HIC when they had one. CONCLUSION: In France, the health insurance system aiming
      at protecting all, including undocumented migrants, leads to a prompt access to
      HIC for migrants from sub-Saharan Africa. Nevertheless, this access may be
      impaired by administrative and social insecurities.

PMID- 29447258
TI  - The time-series behavior of neutrophil-to-lymphocyte ratio is useful as a
      predictive marker in non-small cell lung cancer.
AB  - BACKGROUND: Nivolumab improves the survival of advanced non-small cell lung
      cancer (NSCLC), but a significant number of patients still fail to benefit from
      this treatment. In this study, we evaluated the efficacy of the time-series
      behavior of neutrophil-to-lymphocyte ratio (NLR) in a complete blood count from
      advanced NSCLC patients as a predictive marker of the anticancer effect of
      nivolumab. METHODS: We performed a retrospective review of medical records and
      collected data on patients with advanced NSCLC treated with nivolumab as second-
      and further-line treatments from December 2015 to March 2017. The NLRs were
      calculated before each treatment cycle for four cycles. These parameters were
      tested for its association with the overall survival (OS), progression-free
      survival (PFS) and time to treatment failure (TTF). RESULTS: Nineteen patients
      were treated with nivolumab. Stratified by the response to nivolumab, the median
      OS was 2.8 months in progressive disease (PD) and 14.0 months in non-PD (p =
      0.002). Before discontinuation of PD or toxicity, an NLR is rising from baseline
      in 5 out of 7 patients with PD and all of 4 patients with discontinuation due to
      toxicity. Patients with an >30% increase in NLR were associated with a
      significantly shorter TTF compared with those with stable or decrease in NLR both
      after first cycle (p = 0.014) and second cycle (p < 0.001). CONCLUSIONS: The NLR
      is suggested to be useful not only as a prognostic marker but also as a
      predictive marker for treatment with nivolumab. Further prospective study is
      warranted to develop a predictive algorithm to detect PD cases as early as
      possible by focusing the time-series behavior of NLR.

PMID- 29447259
TI  - Medical professionalism of foreign-born and foreign-trained physicians under
      close scrutiny: A qualitative study with stakeholders in Germany.
AB  - Hospitals in Germany employ increasing numbers of foreign-born and foreign
      trained (FB&FT) physicians. Studies have investigated how FB&FT physicians
      experience their professional integration into the German healthcare system,
      however, the perspectives of stakeholders working with and shaping the work
      experiences of FB&FT physicians in German hospitals have so far been neglected.
      This study explores relevant stakeholders' opinions and attitudes towards FB&FT
      physicians-which likely influence how these physicians settle in-and how these
      opinions were formed. We conducted a qualitative interview study with 25
      stakeholders working in hospitals or in health policy development. The interviews
      were analyzed within a constructivist research paradigm using methods derived
      from Grounded Theory (situational analysis as well as open, axial and selective
      coding). We found that stakeholders tended to focus on problems in FB&FT
      physicians' work performance. Participants criticized FB&FT physicians' work for
      deviating from presumably shared professional standards (skill or knowledge and
      behavioral standards). The professional standards invoked to justify problem
      focused statements comprised the definition of an ideal behavior, attitude or
      ability and a tolerance range that was adapted in a dynamic process. Behavior
      falling outside the tolerance range was criticized as unacceptable, requiring
      action to prevent similar deviations in the future. Furthermore, we derived three
      strategies (minimization, homogenization and quality management) proposed by
      participants to manage deviations from assumed professional standards by FB&FT
      physicians. We critically reflect on the social processes of evaluation and
      problematization and question the legitimacy of professional standards invoked.
      We also discuss discriminatory tendencies visible in evaluative statements of
      some participants as well as in some of the strategies proposed. We suggest it
      will be key to develop and implement better support strategies for FB&FT
      physicians while also addressing problematic attitudes within the receiving
      system to further professional integration.

PMID- 29447260
TI  - Optimal dose reduction algorithm using an attenuation-based tube current
      modulation method for cone-beam CT imaging.
AB  - To reduce the radiation dose given to patients, a tube current modulation (TCM)
      method has been widely used in diagnostic CT systems. However, the TCM method has
      not yet been applied to a kV-CBCT system on a LINAC machine. The purpose of this
      study is to investigate if a TCM method would be desirable in a kV-CBCT system
      for image-guided radiation therapy (IGRT) or not. We have developed an
      attenuation-based TCM method using prior knowledge from planning CT images of
      patients. The TCM method can provide optimized dose reductions without degrading
      image quality for kV-CBCT imaging. Here, we investigate whether or not our
      suggested TCM method is desirable to use in kV-CBCT systems to confirm and revise
      the exact position of a patient for IGRT. Patients go through diagnostic CT scans
      for RT planning; therefore, using information from prior CT images can enable
      estimations of the total X-ray attenuation through a patient's body in a CBCT
      setting for radiation treatment. Having this planning CT image allows to use the
      proposed TCM method in RT. The proposed TCM method provides a minimal amount of
      current for each projection, as well as total current, required to reconstruct
      the current modulated CBCT image with an image quality similar to that of CBCT.
      After applying a calculated TCM current for each projection, projection images
      were acquired and the current modulated CBCT image was reconstructed using a FDK
      algorithm. To validate the proposed approach, we used a numerical XCAT phantom
      and a real ATOM phantom and evaluated the performance of the proposed method via
      visual and quantitative image quality metrics. The organ dose due to imaging
      radiation was calculated in both cases and compared using the GATE simulation
      toolkit. As shown in the quantitative evaluation, normalized noise and SSIM
      values of the TCM were similar to those of conventional CBCT images. In addition,
      the proposed TCM method yielded comparable image quality to that of conventional
      CBCT images for both simulations and experimental studies as organ doses were
      decreased. We have successfully demonstrated the feasibility and dosimetric merit
      of a prototypical TCM method for kV-CBCT via simulations and experimental study.
      The results indicate that the proposed TCM method and overall framework can be a
      viable option for CBCT imaging that utilizes an optimal dose reduction without
      degrading image quality. Thus, this method reduces the probability for side
      effects due to radiation exposure.

PMID- 29447261
TI  - Relationship between serum bilirubin levels and cardiovascular disease.
AB  - We tested the hypothesis that higher levels of bilirubin, a bile pigment with
      antioxidant properties, are associated with a decreased risk of cardiovascular
      disease (CVD). This study analyzed data from the Korean Health and Genome Study
      to examine the association between serum total bilirubin (TB) on CVD and CVD
      death. Serum TB was measured in a total of 8,844 subjects (4,196 males and 4,648
      females) and evaluated for the development of new onset CVD from 2001 to 2012
      (mean 8.1 years of follow-up). During the follow-up period, 689 cases of incident
      CVD (7.8%) were identified, and the prevalence of metabolic syndrome (MetS) at
      baseline was 26.1%. The prevalence of MetS decreased across bilirubin tertile
      categories. In addition to MetS itself, individual components of MetS
      significantly decreased with increased bilirubin tertiles. Moreover, the
      incidence of CVD decreased across bilirubin tertile categories. The hazard ratios
      (HRs) for developing coronary heart disease (CHD, HR 0.769, 95% CI 0.655-1.000)
      and CVD death (HR 0.513, 95% CI 0.267-0.985) was significantly lower in the
      highest tertile group (> 0.63 mg/dL) in comparison to the lowest tertile group (<
      0.44 mg/dL) after adjusting for all confounding variables. In the present
      longitudinal study, a significant negative relationship was demonstrated between
      baseline bilirubin levels and incident CHD and CVD death.

PMID- 29447262
TI  - Long-term use of cover crops and no-till shift soil microbial community life
      strategies in agricultural soil.
AB  - Reducing tillage and growing cover crops, widely recommended practices for
      boosting soil health, have major impacts on soil communities. Surprisingly little
      is known about their impacts on soil microbial functional diversity, and
      especially so in irrigated Mediterranean ecosystems. In long-term experimental
      plots at the West Side Research and Extension Center in California's Central
      Valley, we characterized soil microbial communities in the presence or absence of
      physical disturbance due to tillage, in the presence or absence of cover crops,
      and at three depths: 0-5, 5-15 and 15-30 cm. This characterization included qPCR
      for bacterial and archaeal abundances, DNA sequencing of the 16S rRNA gene, and
      phylogenetic estimation of two ecologically important microbial traits (rRNA gene
      copy number and genome size). Total (bacterial + archaeal) diversity was higher
      in no-till than standard till; diversity increased with depth in no-till but
      decreased with depth in standard till. Total bacterial numbers were higher in
      cover cropped plots at all depths, while no-till treatments showed higher numbers
      in 0-5 cm but lower numbers at lower depths compared to standard tillage. Trait
      estimates suggested that different farming practices and depths favored
      distinctly different microbial life strategies. Tillage in the absence of cover
      crops shifted microbial communities towards fast growing competitors, while no
      till shifted them toward slow growing stress tolerators. Across all treatment
      combinations, increasing depth resulted in a shift towards stress tolerators.
      Cover crops shifted the communities towards ruderals-organisms with wider
      metabolic capacities and moderate rates of growth. Overall, our results are
      consistent with decreasing nutrient availability with soil depth and under no
      till treatments, bursts of nutrient availability and niche homogenization under
      standard tillage, and increases in C supply and variety provided by cover crops.
      Understanding how agricultural practices shift microbial abundance, diversity and
      life strategies, such as presented here, can assist with designing farming
      systems that can support high yields, while enhancing C sequestration and
      increasing resilience to climate change.

PMID- 29447263
TI  - Insurance status and cancer treatment mediate the association between
      race/ethnicity and cervical cancer survival.
AB  - Cervical cancer outcomes remain poor among disadvantaged populations, including
      ethnic minorities, low-income, and underinsured women. The aim of this study was
      to evaluate the mechanisms that underlie the observed association between
      race/ethnicity and cervical cancer survival. We identified 13,698 women, ages 21
      to 64 years, diagnosed with stages I-III primary cervical cancer between 2007
      2013 in Surveillance, Epidemiology, and End Results (SEER). Multivariable Cox
      proportional hazards regression models evaluated associations between
      race/ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Other) and
      cervical cancer-specific mortality. We conducted mediation analysis to calculate
      the mediation proportion and its 95% confidence interval. Non-Hispanic black
      women had an increased risk of cervical cancer-specific mortality (HR: 1.23, 95%
      CI: 1.08-1.39), and Hispanic women a decreased risk of dying from their disease
      (HR: 0.82, 95% CI: 0.72-0.93), compared with non-Hispanic white. The estimated
      proportion of excess cervical cancer mortality for non-Hispanic black women
      relative to non-Hispanic white women that was mediated by insurance was 18.6% and
      by treatment was 47.2%. Furthermore, non-Hispanic black women were more likely to
      receive radiation and less likely to receive surgery for early-stage disease. In
      this population-based study we found that some of the excess cervical cancer
      specific mortality for non-Hispanic black women is mediated by factors such as
      insurance status and treatment. These findings suggest that enhancing existing
      insurance coverage and ensuring equal and adequate treatment in all women may be
      a key strategy for improving cervical cancer outcomes.

PMID- 29447264
TI  - Ebselen alleviates testicular pathology in mice with Zika virus infection and
      prevents its sexual transmission.
AB  - Despite the low case fatality, Zika virus (ZIKV) infection has been associated
      with microcephaly in infants and Guillain-Barre syndrome. Antiviral and vaccine
      developments against ZIKV are still ongoing; therefore, in the meantime,
      preventing the disease transmission is critical. Primarily transmitted by Aedes
      species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice
      lacking interferon-alpha/beta and -gamma receptors to study the testicular
      pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively
      damaged mouse testes, increased testicular oxidative stress as indicated by the
      levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4,
      spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines
      including IL-1beta, IL-6, and G-CSF. We then evaluated the potential role of the
      antioxidant ebselen (EBS) in alleviating the testicular pathology with ZIKV
      infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative
      stress, leucocyte infiltration and production of pro-inflammatory response.
      Furthermore, it improved testicular pathology and prevented the sexual
      transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is
      currently in clinical trials for various diseases. ZIKV infection could be on the
      list for potential use of EBS, for alleviating the testicular pathogenesis with
      ZIKV infection and preventing its sexual transmission.

PMID- 29447266
TI  - Engineered resistance to Nosema bombycis by in vitro expression of a single-chain
      antibody in Sf9-III cells.
AB  - Nosema bombycis is a destructive, obligate intracellular parasite of the Bombyx
      mori. In this study, a single-chain variable fragment (scFv) dependent technology
      is developed for the purpose of inhibiting parasite proliferation in insect
      cells. The scFv-G4, which we prepared from a mouse G4 monoclonal antibody, can
      target the N. bombycis spore wall protein 12 (NbSWP12). Indirect
      immunofluorescence assays showed that NbSWP12 located mainly on the outside of
      the N. bombycis cytoskeleton, although some of it co-localized with beta-tubulin
      in the meront-stage of parasites. When meront division began, NbSWP12 became
      concentrated at both ends of each meront. Western blotting showed that scFv-G4
      could express in Sf9-III cells and recognized native NbSWP12. The transgenic Sf9
      III cell line showed better resistance than the controls when challenged with N.
      bombycis, indicating that NbSWP12 is a promising target in this parasite and this
      scFv dependent strategy could be a solution for construction of N. bombycis
      resistant Bombyx mori.

PMID- 29447265
TI  - Dynamic remodeling of lipids coincides with dengue virus replication in the
      midgut of Aedes aegypti mosquitoes.
AB  - We describe the first comprehensive analysis of the midgut metabolome of Aedes
      aegypti, the primary mosquito vector for arboviruses such as dengue, Zika,
      chikungunya and yellow fever viruses. Transmission of these viruses depends on
      their ability to infect, replicate and disseminate from several tissues in the
      mosquito vector. The metabolic environments within these tissues play crucial
      roles in these processes. Since these viruses are enveloped, viral replication,
      assembly and release occur on cellular membranes primed through the manipulation
      of host metabolism. Interference with this virus infection-induced metabolic
      environment is detrimental to viral replication in human and mosquito cell
      culture models. Here we present the first insight into the metabolic environment
      induced during arbovirus replication in Aedes aegypti. Using high-resolution mass
      spectrometry, we have analyzed the temporal metabolic perturbations that occur
      following dengue virus infection of the midgut tissue. This is the primary site
      of infection and replication, preceding systemic viral dissemination and
      transmission. We identified metabolites that exhibited a dynamic-profile across
      early-, mid- and late-infection time points. We observed a marked increase in the
      lipid content. An increase in glycerophospholipids, sphingolipids and fatty acyls
      was coincident with the kinetics of viral replication. Elevation of glycerolipid
      levels suggested a diversion of resources during infection from energy storage to
      synthetic pathways. Elevated levels of acyl-carnitines were observed, signaling
      disruptions in mitochondrial function and possible diversion of energy
      production. A central hub in the sphingolipid pathway that influenced
      dihydroceramide to ceramide ratios was identified as critical for the virus life
      cycle. This study also resulted in the first reconstruction of the sphingolipid
      pathway in Aedes aegypti. Given conservation in the replication mechanisms of
      several flaviviruses transmitted by this vector, our results highlight
      biochemical choke points that could be targeted to disrupt transmission of
      multiple pathogens by these mosquitoes.

PMID- 29447267
TI  - Tricked or trapped-Two decoy mechanisms in host-pathogen interactions.

PMID- 29447268
TI  - Circulating small non-coding RNAs reflect IFN status and B cell hyperactivity in
      patients with primary Sjogren's syndrome.
AB  - BACKGROUND: Considering the important role of miRNAs in the regulation of post
      transcriptional expression of target genes, we investigated circulating small non
      coding RNAs (snc)RNA levels in patients with primary Sjogren's syndrome (pSS). In
      addition we assessed if serum sncRNA levels can be used to differentiate patients
      with specific disease features. METHODS: Serum RNA was isolated from 37 pSS
      patients as well as 21 patients with incomplete Sjogren's Syndrome (iSS) and 17
      healthy controls (HC) allocated to two independent cohorts: discovery and
      validation. OpenArray profiling of 758 sncRNAs was performed in the discovery
      cohort. Selected sncRNAs were measured in the validation cohort using single
      assay RT-qPCR. In addition, unsupervised hierarchical clustering was performed
      within the pSS group. RESULTS: Ten sncRNAs were differentially expressed between
      the groups in the array. In the validation cohort, we confirmed the increased
      expression of U6-snRNA and miR-661 in the iSS group as compared to HC. We were
      unable to validate differential expression of any miRNAs in the pSS group.
      However, within this group several miRNAs correlated with laboratory parameters.
      Unsupervised clustering distinguished three clusters of pSS patients. Patients in
      one cluster showed significantly higher serum IgG, prevalence of anti-SSB
      autoantibodies, IFN-score, and decreased leukocyte counts compared to the two
      other clusters. CONCLUSION: We were unable to identify any serum sncRNAs with
      differential expression in pSS patients. However, we show that circulating miRNA
      levels are associated with disease parameters in pSS patients and can be used to
      distinguish pSS patients with more severe B cell hyperactivity. As several of
      these miRNAs are implicated in the regulation of B cells, they may play a role in
      the perpetuation of the disease.

PMID- 29447269
TI  - Correction: Viable adhered Staphylococcus aureus highly reduced on novel
      antimicrobial sutures using chlorhexidine and octenidine to avoid surgical site
      infection (SSI).
AB  - [This corrects the article DOI: 10.1371/journal.pone.0190912.].

PMID- 29447270
TI  - Correction: Hospitalizations due to unintentional transport injuries among
      Aboriginal population of British Columbia, Canada: Incidence, changes over time
      and ecological analysis of risk markers.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0191384.].

PMID- 29447272
TI  - Reduced translucency and the addition of black patterns increase the catch of the
      greenhouse whitefly, Trialeurodes vaporariorum, on yellow sticky traps.
AB  - The greenhouse whitefly Trialeurodes vaporariorum (Westwood) (Hemiptera:
      Aleyrodidae) is a pest of a wide range of vegetable and ornamental crops in
      greenhouses around the world. Yellow sticky traps are highly attractive to flying
      adults and so are frequently used to monitor the pest. Our aim was to test
      whether changes in trap translucency or the addition of printed black patterns
      could increase the catch on yellow sticky traps in greenhouses. Field trials were
      carried out in commercial crops of strawberry and tomato under glass over three
      years. Reduced trap translucency increased trap catches by a factor of 1.5 to 7.0
      and the catch increased significantly for both females and males. Spectrometer
      measurements showed that the increased catch was consistent with an increased
      landing stimulus from a colour opponency mechanism i.e. the ratio of energy from
      500-640 nm to the energy from 300-500 nm. Printed black patterns increased trap
      catches on specific types of trap, by a factor of 1.4 to 2.3, and the catch
      increased significantly for both females and males. The patterns increased trap
      catch on moderately translucent traps, but decreased trap catch on less
      translucent traps. The evidence points to a contrast/edge effect of pattern, but
      laboratory experiments are needed to clarify this. Exploitation of these
      translucency and pattern effects could improve the efficacy of yellow traps for
      monitoring and mass trapping in crops.

PMID- 29447271
TI  - Parents' knowledge, beliefs, and acceptance of the HPV vaccination in relation to
      their socio-demographics and religious beliefs: A cross-sectional study in
      Thailand.
AB  - Thailand has one of the world's highest prevalence of cervical cancer, mainly
      caused by the human papillomavirus (HPV). HPV infections can successfully be
      prevented by vaccination, which is available at a cost but not yet implemented in
      the national vaccination program. Parents play a critical role in deciding
      whether to vaccinate their child against HPV. Thus, the aim was to examine the
      association between parents' knowledge, beliefs, and acceptance of the HPV
      vaccination for their daughters, considering their socio-demographics and
      religious beliefs. A cross-sectional design was used among three schools in
      Thailand: Nakorn Phatom province (suburban) and Bangkok (urban). Parents of 9-12
      year-old daughters completed the questionnaires, guided by the Health Belief
      Model. In total, 359 parents completed the questionnaires; of those, 301 were
      included in the final analyses. The ordinary least squares (OLS) regression
      analysis showed that background knowledge of HPV and the HPV vaccine was
      positively related to knowledge of HPV and cervical cancer. For beliefs,
      knowledge was positively associated with susceptibility (i.e., parents' perceived
      risk of an HPV infection/ related disease), severity, and benefit. However,
      knowledge was not significantly related to barriers. For acceptance, higher
      susceptibility and benefit were related to higher acceptance, and greater
      knowledge was associated with higher acceptance. Thus, we found associations
      between parents' knowledge, beliefs, and acceptance of the HPV vaccination for
      their daughters, considering their socio-demographics and religious beliefs.
      Parents, who reported religion as important, as opposed to those who did not,
      were more favorable toward the HPV vaccination. Four out of ten mothers had never
      undergone a cervical cancer screening, but most had accepted previous childhood
      vaccinations for their daughters. The overall acceptance of the vaccine was high,
      and we believe our results are promising for future implementation of the HPV
      vaccination in the national childhood vaccination program in Thailand.

PMID- 29447273
TI  - Molecular epidemiology and drug sensitivity pattern of Mycobacterium tuberculosis
      strains isolated from pulmonary tuberculosis patients in and around Ambo Town,
      Central Ethiopia.
AB  - INTRODUCTION: Tuberculosis (TB) is caused by M. tuberculosis complex and remains
      a major global public health problem. The epidemic remains a threat to sub
      Saharan Africa, including Ethiopia, with further emergence of drug resistant TB.
      We investigated the drug sensitivity pattern and molecular epidemiology of
      mycobacterial strains isolated from pulmonary TB patients in and around Ambo town
      in Oromia Region, Central Ethiopia. METHODS: A cross-sectional study was
      conducted involving 105 consecutive new smear positive pulmonary TB patients
      diagnosed at Ambo Hospital and surrounding Health Centers between May 2014 and
      March 2015 upon informed consent. Sputum samples were cultured on Lowenstein
      Jensen (LJ) media using standard techniques to isolate mycobacteria. Region of
      difference 9 (RD9)-based polymerase chain reaction (PCR) and spoligotyping was
      employed for the identification of the isolates at species and strain levels. The
      spoligotype patterns were entered into the SITVIT database to determine Octal and
      SIT (Spoligotyping International Typing) numbers for each strain. The sensitivity
      of the isolates to isoniazid (INH), rifampicin (RIF), ethambutol (ETB) and
      streptomycin (STM) was evaluated on LJ-medium with the indirect proportion
      method. RESULTS: Cultures were positive in 86/105 (82%) of newly diagnosed smear
      positive pulmonary TB cases. All of the 86 isolates were confirmed as M.
      tuberculosis. The majority (76.7%) of them were clustered into seven groups while
      the rest (23.3%) appeared unique. The most predominant Spoligotypes were SIT53
      and SIT149, consisting of 24.4% and 20.9% of the isolates, respectively.
      Assigning of the isolates to family using SPOTCLUST software revealed that 45.3%
      of the isolates belonged to T1, 23.3% to T3 and 13% to CAS family. The majority
      (76.7%) of the M. tuberculosis isolates were susceptible to all the four drugs.
      Any resistance to any one of the four drugs was detected in 23.3% of the
      isolates. The highest proportion of any resistance was observed against isoniazid
      (9.3%) and ethambutol (7%). There was only a single case (1.2%) of multidrug
      resistant/rifampicin resistant (MDR/RR) TB. CONCLUSION: The majority of the
      isolates were clustered suggesting on-going active transmission in the study
      area. Mono resistance is relatively prevalent while the magnitude of MDR/RR-TB
      was found to be lower than in previous studies.

PMID- 29447274
TI  - Health literacy of hospital patients using a linguistically validated Croatian
      version of the Newest Vital Sign screening test (NVS-HR).
AB  - The Newest Vital Sign (NVS) is a simple, quick and accurate screening test for
      health literacy (HL). It has been validated for different languages but, to date,
      not for the Croatian language. The aim of this study was to develop a
      linguistically validated Croatian version of the NVS and to use it at a later
      stage in a pilot study of health literacy assessment of hospital patients in
      Croatia. A full linguistic validation procedure was applied, including forward
      and backward translation, expert panel review, cognitive interview with 10
      respondents from general population, and full involvement in the procedure of one
      of the screening test developers, the lead author of the NVS-UK version. HL
      testing on 100 hospital patients (55% women, median age 63.5 years) revealed 58%
      of patients had less than adequate HL level (scores less than 4), and mean NVS
      total score was 3.34. A positive significant association was observed between HL
      and educational level (p = 0.002). A high percentage of patients (92%) did not
      object to being tested for HL by their primary care physician or in hospital, and
      99% of patients would recommend HL testing among patients in general. The
      respondents' positive views on HL testing and mean completion time of 4 minutes
      indicate that the Croatian version of the NVS (NVS-HR) could be recommended for
      use in both clinical and research settings in Croatia.

PMID- 29447275
TI  - Correction: Hong Kong Hospital Authority resource efficiency evaluation: Via a
      novel DEA-Malmquist model and Tobit regression model.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184211.].

PMID- 29447277
TI  - Correction: Generation of G protein-coupled receptor antibodies differentially
      sensitive to conformational states.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187306.].

PMID- 29447276
TI  - Mesenchymal stem cell-derived exosomes have altered microRNA profiles and induce
      osteogenic differentiation depending on the stage of differentiation.
AB  - Human mesenchymal stem cell (hMSC)-derived exosomes have shown regenerative
      effects, but their role in osteogenesis and the underlying mechanism are yet to
      be determined. In this study, we examined the time-course secretion of exosomes
      by hMSCs during the entire process of osteogenic differentiation. Exosomes
      derived from hMSCs in various stages of osteogenic differentiation committed
      homotypic cells to differentiate towards osteogenic lineage, but only exosomes
      from late stages of osteogenic differentiation induced extracellular matrix
      mineralisation. Exosomes from expansion and early and late stages of osteogenic
      differentiation were internalised by a subpopulation of hMSCs. MicroRNA profiling
      revealed a set of differentially expressed exosomal microRNAs from the late stage
      of osteogenic differentiation, which were osteogenesis related. Target prediction
      demonstrated that these microRNAs enriched pathways involved in regulation of
      osteogenic differentiation and general mechanisms how exosomes exert their
      functions, such as "Wnt signalling pathway" and "endocytosis". Taken together,
      the results show that MSCs secrete exosomes with different biological properties
      depending on differentiation stage of their parent cells. The exosomal cargo
      transferred from MSCs in the late stage of differentiation induces osteogenic
      differentiation and mineralisation. Moreover, it is suggested that the regulatory
      effect on osteogenesis by exosomes is at least partly exerted by exosomal
      microRNA.

PMID- 29447278
TI  - An increasing trend of rural infections of human influenza A (H7N9) from 2013 to
      2017: A retrospective analysis of patient exposure histories in Zhejiang
      province, China.
AB  - BACKGROUND: Although investigations have shown that closing live poultry markets
      (LPMs) is highly effective in controlling human influenza A (H7N9) infections,
      many of the urban LPMs were shut down, but rural LPMs remained open. This study
      aimed to compare the proportional changes between urban and rural infections in
      the Zhejiang province from 2013 to 2017 by analyzing the exposure histories of
      human cases. METHODS: All laboratory-confirmed cases of H7N9 from 2013 (the first
      wave) to 2017 (the fifth wave) in the Zhejiang province of China were analyzed.
      Urban and rural infections were defined based on the locations of poultry
      exposure (direct and indirect) in urban areas (central towns) and rural areas
      (towns and villages on the outskirts of cities). A Chi-square trend test was used
      to compare the proportional trend between urban and rural infections over time
      and logistic regression was used to obtain the odds ratio by years. RESULTS: From
      2013 to 2017, a statistically significant trend in rural infections was observed
      (p <0.01). The incremental odds ratio by years of rural infections was 1.59 with
      95% confidence intervals of 1.34 to 1.86. Each year, significant increases in the
      proportion of live poultry transactions in LPMS and poultry processing plants
      were detected in conjunction with an increased proportion of urban and rural
      infections. CONCLUSION: The empirical evidence indicated a need for heightened
      infection control measures in rural areas, such as serving rural farms and
      backyards as active surveillance points for the H7N9 virus. Other potential
      interventions such as the vaccination of poultry and extending the closure of
      LPMs to the provincial level require further careful investigations.

PMID- 29447280
TI  - Practice makes the deficiency of global motion detection in people with pattern
      related visual stress more apparent.
AB  - AIMS: Pattern-related visual stress (PRVS) refers to the perceptual difficulties
      experienced by some individuals when exposed to high contrast striped patterns.
      People with PRVS were reported to have reduced sensitivity to global motion at
      baseline testing and the difference disappears at a second estimate. The present
      study was to investigate the effect of practice on global motion threshold in
      adults with and without PRVS. METHODS: A total of 101 subjects were recruited and
      the Wilkins & Evans Pattern Glare Test was used to determine if a subject had
      PRVS. The threshold to detect global motion was measured with a random dot
      kinematogram. Each subject was measured 5 times at the first visit and again a
      month later. Receiver operating characteristic (ROC) curve analysis was applied
      to show the agreement between the two tests. RESULTS: Twenty-nine subjects were
      classified as having PRVS and 72 were classified as normal. At baseline, the
      threshold to detect global motion was significantly higher in subjects with PRVS
      (0.832 +/- 0.098 vs. 0.618 +/- 0.228, p < 0.001). After 5 sessions, the
      difference between the normal and subjects with PRVS increased (0.767 +/- 0.170
      vs. 0.291 +/- 0.149, p < 0.001). In ROC analysis, the area under the curve (AUC)
      improved from 0.792 at baseline to 0.964 at the fifth session. After a one-month
      break, the difference between normal and subjects with PRVS was still significant
      (0.843 +/- 0.169 vs. 0.407 +/- 0.216, p < 0.001) and the AUC was 0.875.
      CONCLUSION: The ability to detect global motion is impaired in persons with PRVS
      and the difference increased after additional sessions of practice.

PMID- 29447279
TI  - Regulatory T cells in retroviral infections.
AB  - Tight regulation of immune responses is not only critical for preventing
      autoimmune diseases but also for preventing immunopathological damage during
      infections in which overactive immune responses may be more harmful for the host
      than the pathogen itself. Regulatory T cells (Tregs) play a critical role in this
      regulation, which was discovered using the Friend retrovirus (FV) mouse model.
      Subsequent FV studies revealed basic biological information about Tregs,
      including their suppressive activity on effector cells as well as the molecular
      mechanisms of virus-induced Treg expansion. Treg suppression not only limits
      immunopathology but also prevents complete elimination of pathogens contributing
      to chronic infections. Therefore, Tregs play a complex role in the pathogenesis
      of persistent retroviral infections. New therapeutic concepts to reactivate
      effector T-cell responses in chronic viral infections by manipulating Tregs also
      came from work with the FV model. This knowledge initiated many studies to
      characterize the role of Tregs in HIV pathogenesis in humans, where a complex
      picture is emerging. On one hand, Tregs suppress HIV-specific effector T-cell
      responses and are themselves targets of infection, but on the other hand, Tregs
      suppress HIV-induced immune hyperactivation and thus slow the infection of
      conventional CD4+ T cells and limit immunopathology. In this review, the basic
      findings from the FV mouse model are put into perspective with clinical and basic
      research from HIV studies. In addition, the few Treg studies performed in the
      simian immunodeficiency virus (SIV) monkey model will also be discussed. The
      review provides a comprehensive picture of the diverse role of Tregs in different
      retroviral infections and possible therapeutic approaches to treat retroviral
      chronicity and pathogenesis by manipulating Treg responses.

PMID- 29447281
TI  - Peptidic inhibitors of insulin-degrading enzyme with potential for dermatological
      applications discovered via phage display.
AB  - Insulin-degrading enzyme (IDE) is an atypical zinc-metalloendopeptidase that
      hydrolyzes insulin and other intermediate-sized peptide hormones, many of which
      are implicated in skin health and wound healing. Pharmacological inhibitors of
      IDE administered internally have been shown to slow the breakdown of insulin and
      thereby potentiate insulin action. Given the importance of insulin and other IDE
      substrates for a variety of dermatological processes, pharmacological inhibitors
      of IDE suitable for topical applications would be expected to hold significant
      therapeutic and cosmetic potential. Existing IDE inhibitors, however, are
      prohibitively expensive, difficult to synthesize and of undetermined toxicity.
      Here we used phage display to discover novel peptidic inhibitors of IDE, which
      were subsequently characterized in vitro and in cell culture assays. Among
      several peptide sequences tested, a cyclic dodecapeptide dubbed P12-3A was found
      to potently inhibit the degradation of insulin (Ki = 2.5 +/- 0.31 MUM) and other
      substrates by IDE, while also being resistant to degradation, stable in
      biological milieu, and highly selective for IDE. In cell culture, P12-3A was
      shown to potentiate several insulin-induced processes, including the
      transcription, translation and secretion of alpha-1 type I collagen in primary
      murine skin fibroblasts, and the migration of keratinocytes in a scratch wound
      migration assay. By virtue of its potency, stability, specificity for IDE, low
      cost of synthesis, and demonstrated ability to potentiate insulin-induced
      processes involved in wound healing and skin health, P12-3A holds significant
      therapeutic and cosmetic potential for topical applications.

PMID- 29447282
TI  - Addition of m6A to SV40 late mRNAs enhances viral structural gene expression and
      replication.
AB  - Polyomaviruses are a family of small DNA tumor viruses that includes several
      pathogenic human members, including Merkel cell polyomavirus, BK virus and JC
      virus. As is characteristic of DNA tumor viruses, gene expression in
      polyomaviruses is temporally regulated into an early phase, consisting of the
      viral regulatory proteins, and a late phase, consisting of the viral structural
      proteins. Previously, the late transcripts expressed by the prototypic
      polyomavirus simian virus 40 (SV40) were reported to contain several adenosines
      bearing methyl groups at the N6 position (m6A), although the precise location of
      these m6A residues, and their phenotypic effects, have not been investigated.
      Here, we first demonstrate that overexpression of the key m6A reader protein
      YTHDF2 induces more rapid viral replication, and larger viral plaques, in SV40
      infected BSC40 cells, while mutational inactivation of the endogenous YTHDF2
      gene, or the m6A methyltransferase METTL3, has the opposite effect, thus
      suggesting a positive role for m6A in the regulation of SV40 gene expression. To
      directly test this hypothesis, we mapped sites of m6A addition on SV40
      transcripts and identified two m6A sites on the viral early transcripts and
      eleven m6A sites on the late mRNAs. Using synonymous mutations, we inactivated
      the majority of the m6A sites on the SV40 late mRNAs and observed that the
      resultant viral mutant replicated more slowly than wild type SV40. Alternative
      splicing of SV40 late mRNAs was unaffected by the reduction in m6A residues and
      our data instead suggest that m6A enhances the translation of viral late
      transcripts. Together, these data argue that the addition of m6A residues to the
      late transcripts encoded by SV40 plays an important role in enhancing viral gene
      expression and, hence, replication.

PMID- 29447283
TI  - Gp96 deficiency affects TLR4 functionality and impairs ERK and p38
      phosphorylation.
AB  - Gp96 is an endoplasmic reticulum chaperone for multiple protein substrates. Its
      lack in intestinal macrophages of Crohn's disease (CD) patients is correlated
      with loss of tolerance against the host gut flora. Gp96 has been stablished to be
      an essential chaperone for Toll-like receptors (TLRs). We studied the impact of
      gp96-knockdown on TLR-function in macrophages. TLR2 and TLR4 expression was only
      decreased but not abolished when gp96 was knocked-down in cell lines, whereas in
      a monocyte/macrophage specific knock-out mouse model (LysMCre) TLR4 was
      abolished, while TLR2 was still present. Lipopolysaccharide (LPS)-induced NF
      kappaB activation was still observed in the absence of gp96, and gp96-deficient
      macrophages were able to up-regulate surface TLR4 upon LPS treatment, suggesting
      that there is another chaperone involved in the folding of TLR4 upon stress
      responses. Moreover, LPS-dependent pro-inflammatory cytokines were still
      expressed, although to a lesser extent in the absence of gp96, which reinforces
      the fact that gp96 is involved in regulating signaling cascades downstream of
      TLR4 are impaired upon loss of gp96. In addition, we have also found a reduced
      phosphorylation of ERK and p38 kinases and an impaired response upon CSF1R
      activation in gp96 deficient macrophages. Our findings indicate that the loss of
      gp96 not only impairs TLR4 signaling, but is also associated with a diminished
      phosphorylation of ERK and mitogen-activated stress kinases resulting in an
      impaired signalling through several receptors, including CSF1R.

PMID- 29447286
TI  - Modeling nearshore-offshore exchange in Lake Superior.
AB  - Lake Superior's ecosystem includes distinct nearshore and offshore food webs
      linked by hydrodynamic processes that transport water and tracers along and
      across shore. The scales over which these processes occur and their sensitivity
      to increasing summer surface temperatures are not well understood. This study
      investigated horizontal mixing between nearshore and offshore areas of Lake
      Superior over the 10-year period from 2003 to 2012 using a realistically forced
      three-dimensional numerical model and virtual tracers. An age tracer was used to
      characterize the time scales of horizontal mixing between nearshore areas of the
      lake where water depth is less than 100 m and deeper areas. The age of water in
      nearshore areas increased and decreased in an annual cycle corresponding to the
      lake's dimictic cycle of vertical mixing and stratification. Interannual
      variability of mixing in the isothermal period was significantly correlated to
      average springtime wind speed, whereas variability during the stratified season
      was correlated to the average summer surface temperature. Dispersal of a passive
      tracer released from nine locations around the model lake's perimeter was more
      extensive in late summer when stratification was established lakewide than in
      early summer. The distribution of eddies resolved in the model reflected
      differences between the early and late summer dispersal patterns. In the eastern
      part of the lake dispersal was primarily alongshore, reflecting counterclockwise
      coastal circulation. In the western part of the lake, cross-shore mixing was
      enhanced by cross-basin currents.

PMID- 29447285
TI  - Murine cytomegalovirus degrades MHC class II to colonize the salivary glands.
AB  - Cytomegaloviruses (CMVs) persistently and systemically infect the myeloid cells
      of immunocompetent hosts. Persistence implies immune evasion, and CMVs evade CD8+
      T cells by inhibiting MHC class I-restricted antigen presentation. Myeloid cells
      can also interact with CD4+ T cells via MHC class II (MHC II). Human CMV (HCMV)
      attacks the MHC II presentation pathway in vitro, but what role this evasion
      might play in host colonization is unknown. We show that Murine CMV (MCMV) down
      regulates MHC II via M78, a multi-membrane spanning viral protein that captured
      MHC II from the cell surface and was necessary although not sufficient for its
      degradation in low pH endosomes. M78-deficient MCMV down-regulated MHC I but not
      MHC II. After intranasal inoculation, it showed a severe defect in salivary gland
      colonization that was associated with increased MHC II expression on infected
      cells, and was significantly rescued by CD4+ T cell loss. Therefore MCMV requires
      CD4+ T cell evasion by M78 to colonize the salivary glands, its main site of long
      term shedding.

PMID- 29447284
TI  - Influenza interaction with cocirculating pathogens and its impact on
      surveillance, pathogenesis, and epidemic profile: A key role for mathematical
      modelling.
AB  - Evidence is mounting that influenza virus interacts with other pathogens
      colonising or infecting the human respiratory tract. Taking into account
      interactions with other pathogens may be critical to determining the real
      influenza burden and the full impact of public health policies targeting
      influenza. This is particularly true for mathematical modelling studies, which
      have become critical in public health decision-making. Yet models usually focus
      on influenza virus acquisition and infection alone, thereby making broad
      oversimplifications of pathogen ecology. Herein, we report evidence of influenza
      virus interactions with bacteria and viruses and systematically review the
      modelling studies that have incorporated interactions. Despite the many studies
      examining possible associations between influenza and Streptococcus pneumoniae,
      Staphylococcus aureus, Haemophilus influenzae, Neisseria meningitidis,
      respiratory syncytial virus (RSV), human rhinoviruses, human parainfluenza
      viruses, etc., very few mathematical models have integrated other pathogens
      alongside influenza. The notable exception is the pneumococcus-influenza
      interaction, for which several recent modelling studies demonstrate the power of
      dynamic modelling as an approach to test biological hypotheses on interaction
      mechanisms and estimate the strength of those interactions. We explore how
      different interference mechanisms may lead to unexpected incidence trends and
      possible misinterpretation, and we illustrate the impact of interactions on
      public health surveillance using simple transmission models. We demonstrate that
      the development of multipathogen models is essential to assessing the true public
      health burden of influenza and that it is needed to help improve planning and
      evaluation of control measures. Finally, we identify the public health,
      surveillance, modelling, and biological challenges and propose avenues of
      research for the coming years.

PMID- 29447288
TI  - Climate change and the northern elephant seal (Mirounga angustirostris)
      population in Baja California, Mexico.
AB  - The Earth's climate is warming, especially in the mid- and high latitudes of the
      Northern Hemisphere. The northern elephant seal (Mirounga angustirostris) breeds
      and haul-outs on islands and the mainland of Baja California, Mexico, and
      California, U.S.A. At the beginning of the 21st century, numbers of elephant
      seals in California are increasing, but the status of Baja California populations
      is unknown, and some data suggest they may be decreasing. We hypothesize that the
      elephant seal population of Baja California is experiencing a decline because the
      animals are not migrating as far south due to warming sea and air temperatures.
      Here we assessed population trends of the Baja California population, and climate
      change in the region. The numbers of northern elephant seals in Baja California
      colonies have been decreasing since the 1990s, and both the surface waters off
      Baja California and the local air temperatures have warmed during the last three
      decades. We propose that declining population sizes may be attributable to
      decreased migration towards the southern portions of the range in response to the
      observed temperature increases. Further research is needed to confirm our
      hypothesis; however, if true, it would imply that elephant seal colonies of Baja
      California and California are not demographically isolated which would pose
      challenges to environmental and management policies between Mexico and the United
      States.

PMID- 29447287
TI  - Strain-specific quantification of root colonization by plant growth promoting
      rhizobacteria Bacillus firmus I-1582 and Bacillus amyloliquefaciens QST713 in non
      sterile soil and field conditions.
AB  - Bacillus amyloliquefaciens QST713 and B. firmus I-1582 are bacterial strains
      which are used as active ingredients of commercially-available soil application
      and seed treatment products Serenade(r) and VOTiVO(r), respectively. These
      bacteria colonize plant roots promoting plant growth and offering protection
      against pathogens/pests. The objective of this study was to develop a qPCR
      protocol to quantitate the dynamics of root colonization by these two strains
      under field conditions. Primers and TaqMan(r) probes were designed based on
      genome comparisons of the two strains with publicly-available and unpublished
      bacterial genomes of the same species. An optimized qPCR protocol was developed
      to quantify bacterial colonization of corn roots after seed treatment. Treated
      corn seeds were planted in non-sterile soil in the greenhouse and grown for 28
      days. Specific detection of bacteria was quantified weekly, and showed stable
      colonization between ~104-105 CFU/g during the experimental period for both
      bacteria, and the protocol detected as low as 103 CFU/g bacteria on roots. In a
      separate experiment, streptomycin-resistant QST713 and rifampicin-resistant I
      1582 strains were used to compare dilution-plating on TSA with the newly
      developed qPCR method. Results also indicated that the presence of natural
      microflora and another inoculated strain does not affect root colonization of
      either one of these strains. The same qPCR protocol was used to quantitate root
      colonization by QST713 and I-1582 in two corn and two soybean varieties grown in
      the field. Both bacteria were quantitated up to two weeks after seeds were
      planted in the field and there were no significant differences in root
      colonization in either bacteria strain among varieties. Results presented here
      confirm that the developed qPCR protocol can be successfully used to understand
      dynamics of root colonization by these bacteria in plants growing in growth
      chamber, greenhouse and the field.

PMID- 29447289
TI  - Correlates of self-harm and suicide attempts in justice-involved young people.
AB  - The purpose of this study was to ascertain the prevalence and correlates of self
      harm among young people in detention in Australia. The sample included 215 (177
      male; 38 female) young people who were in youth detention in the state of
      Victoria, Australia. Participants were administered a series of questionnaires
      related to self-harm, mental health, socio-environmental experiences and
      behaviours. Overall, one-third (33%) of the sample reported previous self-harm
      and 12% reported at least one suicide attempt. In a multivariate logistic
      regression analysis, a history of childhood trauma, contact with mental health
      services, and low educational interest significantly increased the likelihood of
      self-harm. Young people who reported a suicide attempt scored significantly
      higher on the measure of childhood trauma than did youth who had engaged in non
      suicidal self-harm. Findings demonstrate a strong connection between childhood
      traumatic experiences and suicidal behaviours for youth in detention. Trauma
      histories and mental health concerns must be considered when identifying youth at
      increased risk of self-harm.

PMID- 29447290
TI  - A neonatal murine model for evaluation of enterovirus E HY12 virus infection and
      pathogenicity.
AB  - BACKGROUNDS: HY12 viruses are enteroviruses recently isolated from cattle
      characterized by severe respiratory and digestive disease with high morbidity and
      mortality in China. While the viruses exhibit unique biological and molecular
      characters distinct from known enterovirus E, the pathogenicity and viral
      pathogenesis remains largely unknown. METHODS: Neonatal mice of Balb/C, ICR, and
      Kunming strain are infected with HY12 to determine the susceptible mouse strain.
      The minimal infection dose, the virus infection routes, the pathogenicity and
      tissue tropism for HY12 were determined by infecting susceptible mice with HY12
      viruses, and confirmed by different approaches including virus isolation and
      recovery, virus detection, histopathology, and immunohistochemistry. RESULTS: A
      murine model for HY12 infection was successfully established and employed to
      investigate the pathogenicity of HY12 viruses. ICR mouse strain is the most
      susceptible strain for HY12 infection with a minimal infective dose as
      2*106TCID50/mouse. HY12 viruses have the capability of infecting ICR suckling
      mice via all infection routes including intranasal administration, oral
      administration, intraperitoneal injection, subcutaneous injection, and
      intramuscular injection, which are confirmed by the isolation and recovery of
      viruses from HY12-infected mice; detection of viruses by RT-PCR; observations of
      pathological lesions and inflammatory cell infiltrations in the intestine, lung,
      liver, and brain; uncovering of HY12 virus antigens in majority of tissues,
      especially in intestine, lung, and infected brain of mice by immunohistochemistry
      assay. CONCLUSIONS: A neonatal murine model for HY12 infection is successfully
      established for determining the susceptible mouse strain, the minimal infective
      dose, the infection route, the viral pathogenicity and the tropism of HY12, thus
      providing an invaluable model system for elucidating the pathogenesis of HY12
      viruses and the elicited immunity.

PMID- 29447292
TI  - Correction: Gait parameters are differently affected by concurrent smartphone
      based activities with scaled levels of cognitive effort.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185825.].

PMID- 29447291
TI  - Associations between physician home visits for the dying and place of death: A
      population-based retrospective cohort study.
AB  - BACKGROUND: While most individuals wish to die at home, the reality is that most
      will die in hospital. AIM: To determine whether receiving a physician home visit
      near the end-of-life is associated with lower odds of death in a hospital.
      DESIGN: Observational retrospective cohort study, examining location of death and
      health care in the last year of life. SETTING/PARTICIPANTS: Population-level
      study of Ontarians, a Canadian province with over 13 million residents. All
      decedents from April 1, 2010 to March 31, 2013 (n = 264,754). RESULTS: More than
      half of 264,754 decedents died in hospital: 45.7% died in an acute care hospital
      and 7.7% in complex continuing care. After adjustment for multiple factors
      including patient illness, home care services, and days of being at home
      receiving at least one physician home visit from a non-palliative care physician
      was associated with a 47% decreased odds (odds-ratio, 0.53; 95%CI: 0.51-0.55) of
      dying in a hospital. When a palliative care physician specialist was involved,
      the overall odds declined by 59% (odds ratio, 0.41; 95%CI: 0.39-0.43). The same
      model, adjusting for physician home visits, showed that receiving palliative home
      care was associated with a similar reduction (odds ratio, 0.49; 95%CI: 0.47
      0.51). CONCLUSION: Location of death is strongly associated with end-of-life
      health care in the home. Less than one-third of the population, however, received
      end-of-life home care or a physician visit in their last year of life, revealing
      large room for improvement.

PMID- 29447293
TI  - The enzymatic processing of alpha-dystroglycan by MMP-2 is controlled by two
      anchoring sites distinct from the active site.
AB  - Dystroglycan (DG) is a membrane receptor, belonging to the dystrophin
      glycoprotein complex (DGC) and formed by two subunits, alpha-dystroglycan (alpha
      DG) and beta-dystroglycan (beta -DG). The C-terminal domain of alpha-DG and the N
      terminal extracellular domain of beta -DG are connected, providing a link between
      the extracellular matrix and the cytosol. Under pathological conditions, such as
      cancer and muscular dystrophies, DG may be the target of metalloproteinases MMP-2
      and MMP-9, contributing to disease progression. Previously, we reported that the
      C-terminal domain alpha-DG (483-628) domain is particularly susceptible to the
      catalytic activity of MMP-2; here we show that the alpha-DG 621-628 region is
      required to carry out its complete digestion, suggesting that this portion may
      represent a MMP-2 anchoring site. Following this observation, we synthesized an
      alpha-DG based-peptide, spanning the (613-651) C-terminal region. The analysis of
      the kinetic and thermodynamic parameters of the whole and the isolated catalytic
      domain of MMP-2 (cdMMP-2) has shown its inhibitory properties, indicating the
      presence of (at least) two binding sites for the peptide, both located within the
      catalytic domain, only one of the two being topologically distinct from the
      catalytic active groove. However, the different behavior between whole MMP-2 and
      cdMMP-2 envisages the occurrence of an additional binding site for the peptide on
      the hemopexin-like domain of MMP-2. Interestingly, mass spectrometry analysis has
      shown that alpha-DG (613-651) peptide is cleavable even though it is a very poor
      substrate of MMP-2, a feature that renders this molecule a promising template for
      developing a selective MMP-2 inhibitor.

PMID- 29447295
TI  - Progress toward national estimates of police use of force.
AB  - This research builds on three decades of effort to produce national estimates of
      the amount and rate of force used by law enforcement officers in the United
      States. Prior efforts to produce national estimates have suffered from poor and
      inconsistent measurements of force, small and unrepresentative samples, low
      survey and/or item response rates, and disparate reporting of rates of force. The
      present study employs data from a nationally representative survey of state and
      local law enforcement agencies that has a high survey response rate as well as a
      relatively high rate of reporting uses of force. Using data on arrests for
      violent offenses and the number of sworn officers to impute missing data on uses
      of force, we estimate a total of 337,590 use of physical force incidents among
      State and local law enforcement agencies during 2012 with a 95 percent confidence
      interval of +/- 10,470 incidents or +/- 3.1 percent. This article reports the
      extent to which the number and rate of force incidents vary by the type and size
      of law enforcement agencies. Our findings demonstrate the willingness of a large
      proportion of law enforcement agencies to voluntarily report the amount of force
      used by their officers and the relative strengths and weaknesses of the Law
      Enforcement Management and Administrative Statistics (LEMAS) program to produce
      nationally representative information about police behavior.

PMID- 29447294
TI  - Evidence of sex-bias in gene expression in the brain transcriptome of two
      populations of rainbow trout (Oncorhynchus mykiss) with divergent life histories.
AB  - Sex-bias in gene expression is a mechanism that can generate phenotypic variance
      between the sexes, however, relatively little is known about how patterns of sex
      bias vary during development, and how variable sex-bias is between different
      populations. To that end, we measured sex-bias in gene expression in the brain
      transcriptome of rainbow trout (Oncorhynchus mykiss) during the first two years
      of development. Our sampling included from the fry stage through to when O.
      mykiss either migrate to the ocean or remain resident and undergo sexual
      maturation. Samples came from two F1 lines: One from migratory steelhead trout
      and one from resident rainbow trout. All samples were reared in a common garden
      environment and RNA sequencing (RNA-seq) was used to estimate patterns of gene
      expression. A total of 1,716 (4.6% of total) genes showed evidence of sex-bias in
      gene expression in at least one time point. The majority (96.7%) of sex-biased
      genes were differentially expressed during the second year of development,
      indicating that patterns of sex-bias in expression are tied to key developmental
      events, such as migration and sexual maturation. Mapping of differentially
      expressed genes to the O. mykiss genome revealed that the X chromosome is
      enriched for female upregulated genes, and this may indicate a lack of dosage
      compensation in rainbow trout. There were many more sex-biased genes in the
      migratory line than the resident line suggesting differences in patterns of gene
      expression in the brain between populations subjected to different forces of
      selection. Overall, our results suggest that there is considerable variation in
      the extent and identity of genes exhibiting sex-bias during the first two years
      of life. These differentially expressed genes may be connected to developmental
      differences between the sexes, and/or between adopting a resident or migratory
      life history.

PMID- 29447296
TI  - Correction: Perimenopause and emergence of an Alzheimer's bioenergetic phenotype
      in brain and periphery.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185926.].

PMID- 29447297
TI  - Development of a decision aid for cardiopulmonary resuscitation and invasive
      mechanical ventilation in the intensive care unit employing user-centered design
      and a wiki platform for rapid prototyping.
AB  - BACKGROUND: Upon admission to an intensive care unit (ICU), all patients should
      discuss their goals of care and express their wishes concerning life-sustaining
      interventions (e.g., cardiopulmonary resuscitation (CPR)). Without such
      discussions, interventions that prolong life at the cost of decreasing its
      quality may be used without appropriate guidance from patients. OBJECTIVES: To
      adapt an existing decision aid about CPR to create a wiki-based decision aid
      individually adapted to each patient's risk factors; and to document the use of a
      wiki platform for this purpose. METHODS: We conducted three weeks of ethnographic
      observation in our ICU to observe intensivists and patients discussing goals of
      care and to identify their needs regarding decision making. We interviewed
      intensivists individually. Then we conducted three rounds of rapid prototyping
      involving 15 patients and 11 health professionals. We recorded and analyzed all
      discussions, interviews and comments, and collected sociodemographic data. Using
      a wiki, a website that allows multiple users to contribute or edit content, we
      adapted the decision aid accordingly and added the Good Outcome Following
      Attempted Resuscitation (GO-FAR) prediction rule calculator. RESULTS: We added
      discussion of invasive mechanical ventilation. The final decision aid comprises
      values clarification, risks and benefits of CPR and invasive mechanical
      ventilation, statistics about CPR, and a synthesis section. We added the GO-FAR
      prediction calculator as an online adjunct to the decision aid. Although three
      rounds of rapid prototyping simplified the information in the decision aid, 60%
      (n = 3/5) of the patients involved in the last cycle still did not understand its
      purpose. CONCLUSIONS: Wikis and user-centered design can be used to adapt
      decision aids to users' needs and local contexts. Our wiki platform allows other
      centers to adapt our tools, reducing duplication and accelerating scale-up.
      Physicians need training in shared decision making skills about goals of care and
      in using the decision aid. A video version of the decision aid could clarify its
      purpose.

PMID- 29447298
TI  - Effects of voluntary running exercise on bone histology in type 2 diabetic rats.
AB  - The incidence of obesity in children and adolescents, which may lead to type 2
      diabetes, is increasing. Exercise is recommended to prevent and improve diabetes.
      However, little is known about the bone marrow environment at the onset of
      diabetes in the young, and it is unclear whether exercise training is useful for
      maintaining bone homeostasis, such as mechanical and histological properties.
      Thus, this study clarified the histological properties of bone and whether
      exercise contributes to maintaining bone homeostasis at the onset of type 2
      diabetes in rats. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF; n
      = 21) rats as a diabetic model and Long-Evans Tokushima Otsuka (LETO; n = 18)
      rats as a control were assigned randomly to four groups: the OLETF sedentary
      group (O-Sed; n = 11), OLETF exercise group (O-Ex; n = 10), LETO sedentary group
      (L-Sed; n = 9), and LETO exercise group (L-Ex; n = 9). All rats in the exercise
      group were allowed free access to a steel running wheel for 20 weeks (5-25 weeks
      of age). In the glucose tolerance test, blood glucose level was higher in the O
      Sed group than that in the L-Sed and L-Ex groups, and was markedly suppressed by
      the voluntary running exercise of O-Ex rats. The energy to fracture and the two
      dimensional bone volume at 25 weeks of age did not differ significantly among the
      groups, though the maximum breaking force and stiffness were lower in OLETF rats.
      However, bone marrow fat volume was greater in O-Sed than that in L-Sed and L-Ex
      rats, and was markedly suppressed by wheel running in the O-Ex rats. Our results
      indicate that exercise has beneficial effects not only for preventing diabetes
      but also on normal bone remodeling at an early age.

PMID- 29447299
TI  - Effects of breast stimulation for spontaneous onset of labor on salivary oxytocin
      levels in low-risk pregnant women: A feasibility study.
AB  - OBJECTIVES: This preliminary study aimed to 1) determine changes in the salivary
      oxytocin (OT) level during breast stimulation for promoting the spontaneous onset
      of labor in low-risk term pregnancies, and 2) clarify the feasibility of the
      breast stimulation intervention protocol in terms of practicality and
      acceptability. METHODS: We used a single arm trial design. Sixteen low-risk
      pregnant women between 38 and 40 weeks of gestation with cephalic presentation
      participated. They performed breast stimulation for 3 days with an attendant
      midwife in a single maternity hospital. Each breast was stimulated for 15 minutes
      for a total of 1 hour per day. Saliva was collected 10 minutes before the
      intervention and 15, 30, 60, 75, and 90 minutes after the intervention, yielding
      18 samples per woman. RESULTS: Among a total of 282 saliva samples from the 16
      participants, OT level was measured in 142 samples (missing rate: 49.6%). The
      median OT level showed the highest values on day 3 of the breast stimulation,
      with a marked increase 30 min after the intervention. In the mixed models after
      multiple imputation for missing data, the OT level on the first day of
      intervention was significantly lower than that on the third day of intervention.
      Fatigue from breast stimulation decreased on subsequent days, and most of the
      women (75%) felt no discomfort with the protocol. Uterine hyperstimulation was
      not observed. CONCLUSION: Following a 3-day breast stimulation protocol for
      spontaneous onset of labor, the mean OT level showed the highest values on day 3.
      The breast stimulation intervention protocol showed good feasibility in terms of
      practicality and acceptability among the pregnant women. Additional large-scale
      studies are warranted to confirm the protocol's effectiveness.

PMID- 29447300
TI  - Explaining suicide attempt with personality traits of aggression and impulsivity
      in a high risk tribal population of India.
AB  - INTRODUCTION: Suicide is a spectrum of behavior including suicide ideation and
      suicidal attempt and is undoubtedly the outcome of the interaction of several
      factors. The role of two main constructs of human nature, aggression and
      impulsivity, has been discussed broadly in relation to suicide, as endophenotypes
      or traits of personality, in research and in clinical practice across diagnoses.
      The objective of our study was to assess impulsive and aggressive behaviors among
      primitive people of the Idu Mishmi tribe, who are known for high suicide
      completer and attempter rates. METHODS: The study group was comprised of 177
      unrelated Idu Mishmi participants divided into two sets: 39 suicide attempters
      and 138 non-attempters. Data on demographic factors and details of suicide
      attempts were collected. Participants completed a set of instruments for
      assessment of aggression and impulsivity traits. RESULTS: In the Idu Mishimi
      population we screened (n = 177), 22.03% of the individuals had attempted
      suicide, a high percentage. The suicide attempters also showed a significant sex
      difference: 35.9% were male and 64.10% were female (p = .002*). The suicide
      attempters (A) scored significantly higher than non-attempters (NA) on aggression
      (A = 23.93,NA = 18.46) and impulsivity (A = 75.53,NA = 71.59, with p value =
      0.05). The trait impulsiveness showed a significantly higher difference (F (1,
      117) = 7.274) in comparison to aggression (F (1, 117) = 2.647), suggesting a
      profound role of impulsiveness in suicide attempts in the Idu Mishmi population.
      Analysis of sub-traits of aggression and impulsivity revealed significant
      correlations between them. Using different models, multivariate logistic
      regression implied roles of gender (OR = 1.079 (0.05)) and impulsiveness (OR =
      3.355 (0.013)) in suicide attempts. CONCLUSION: Results demonstrate that gender
      and impulsivity are strong risk factors for suicide attempts in the Idu Mishmi
      population.

PMID- 29447302
TI  - In Throwers With Posterior Instability, Rotator Cuff Tears Are Common but Do Not
      Affect Surgical Outcomes.
AB  - In a previous study, compared with throwing athletes with superior labral
      anterior posterior (SLAP) tears, those with concomitant SLAP tears and rotator
      cuff tears (RCTs) had significantly poorer outcome scores and return to play.
      Posterior shoulder instability also occurs in throwing athletes, but no studies
      currently exist regarding outcomes of these patients with concomitant RCTs. The
      authors hypothesized that throwing athletes treated with arthroscopic
      capsulolabral repair for posterior shoulder instability with coexistent rotator
      cuff pathology would have poorer outcome scores and return to play. Fifty-six
      consecutive throwing athletes with unidirectional posterior shoulder instability
      underwent arthroscopic capsulolabral repair. Preoperative and postoperative
      patient-centered outcomes of pain, stability, function, range of motion,
      strength, and American Shoulder and Elbow Surgeons Shoulder (ASES) scores, as
      well as return to play, were evaluated. Patients with and without rotator cuff
      pathology were compared. Forty-three percent (24/56) of throwing athletes had
      rotator cuff pathology in addition to posterior capsulolabral pathology. All RCTs
      were debrided. At a mean of 3 years, there were no differences in preoperative
      and postoperative patient-centered outcomes between those with and without RCTs.
      Return-to-play rates showed no between-group differences; 92% (22/24) of athletes
      with concomitant RCTs returned to sport (P = .414), and 67% (16/24) returned to
      the same level (P = .430). Arthroscopic capsulolabral reconstruction is
      successful in throwing athletes with RCTs treated with arthroscopic debridement.
      Unlike the previous study evaluating throwers outcomes after surgical treatment
      for concomitant SLAP tears and RCTs, the authors found no difference in patient
      reported outcome measures or return to play for throwing athletes with
      concomitant posterior shoulder instability and RCTs. In throwing athletes with
      concomitant posterior instability and RCTs, arthroscopic posterior capsulolabral
      repair with rotator cuff debridement is successful.

PMID- 29447303
TI  - Arthroscopic Anterior Ankle Decompression Is Successful in National Football
      League Players.
AB  - Anterior ankle impingement is a frequent cause of pain and disability in athletes
      with impingement of soft-tissue or osseous structures along the anterior margin
      of the tibiotalar joint during dorsiflexion. In this study, we hypothesized that
      arthroscopic decompression of anterior ankle impingement would result in
      significant, reliable, and durable improvement in pain and range of motion (ROM),
      and would allow National Football League (NFL) players to return to their
      preoperative level of play. We reviewed 29 arthroscopic ankle debridements
      performed by a single surgeon. Each NFL player underwent arthroscopic debridement
      of pathologic soft tissue and of tibial and talar osteophytes in the anterior
      ankle. Preoperative and postoperative visual analog scale (VAS) pain scores,
      American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, and ankle
      ROM were compared; time to return to play (RTP), events missed secondary to
      surgery, and complications were recorded. All athletes returned to the same level
      of NFL play at a mean (SD) of 8.4 (4.1) weeks after surgery and continued playing
      for a mean (SD) of 3.43 (2.57) years after surgery. Mean (SD) VAS pain scores
      decreased significantly (P < .001), to 0.38 (0.89) from 4.21 (1.52). Mean (SD)
      active ankle dorsiflexion increased significantly (P < .001), to 18.86 degrees 
      (2.62 degrees ) from 8.28 degrees  (4.14 degrees ). Mean (SD) AOFAS hindfoot
      scores increased significantly (P < .001), to 97.45 (4.72) from 70.62 (10.39).
      Degree of arthritis (r = 0.305) and age (r = 0.106) were poorly correlated to
      time to RTP. In all cases, arthroscopic debridement of anterior ankle impingement
      resulted in RTP at the same level at a mean of 2 months after surgery. There were
      significant improvements in VAS pain scores, AOFAS hindfoot scores, and ROM.
      Arthroscopic debridement of anterior ankle impingement relieves pain, restores
      ROM and function, and results in reliable RTP in professional football players.

PMID- 29447304
TI  - Shoulder Arthroplasty in Cases of Significant Bone Loss: An Overview.

PMID- 29447305
TI  - Pseudo-Pedicle Heterotopic Ossification From Use of Recombinant Human Bone
      Morphogenetic Protein 2 (rhBMP-2) in Transforaminal Lumbar Interbody Fusion
      Cages.
AB  - We conducted a study to determine the common characteristics of patients who
      developed radiculopathy symptoms and corresponding heterotopic ossification (HO)
      from transforaminal lumbar interbody fusions (TLIF) using recombinant human bone
      morphogenetic protein 2 (rhBMP-2). HO can arise from a disk space with rhBMP-2
      use in TLIF. Formation of bone around nerve roots or the thecal sac can cause a
      radiculopathy with a consistent pattern of symptoms. We identified 38 patients
      (26 males, 12 females) with a mean (SD) age of 50.8 (7.5) years who developed
      radiculopathy symptoms and corresponding HO from TLIF with rhBMP-2 in the disk
      space between 2002 and 2015. To document this complication and improve its
      recognition, we recorded common patterns of symptom development and radiologic
      findings: specifically, time from implantation of rhBMP-2 to symptom development,
      consistency with side of TLIF placement, and radiologic findings. Radicular pain
      generally developed a mean (SD) of 3.8 (1.0) months after TLIF with rhBMP-2.
      Development of radiculopathy symptoms corresponded to consistent "pseudo-pedicle"
      like HO. In all 38 patients, HO arising from the annulotomy site showed a
      distinct pseudo-pedicle pattern encompassing nerve roots and the thecal sac. In
      addition, development of radiculopathy symptoms and corresponding HO appear to be
      independent of amount of rhBMP-2. HO resulting from TLIF with rhBMP-2 in the disk
      space is a pain generator and a recognizable complication that can be diagnosed
      by assessment of symptoms and computed tomography characteristics.

PMID- 29447301
TI  - Esophageal squamous cell carcinoma with low mitochondrial copy number has
      mesenchymal and stem-like characteristics, and contributes to poor prognosis.
AB  - Alterations in mitochondrial DNA (mtDNA) copy numbers in various human cancers
      have been studied, but any such changes in esophageal squamous cell carcinoma
      (ESCC) are not established. In the present study, we investigated the correlation
      of mtDNA copy number with clinicopathologic features, prognosis, and malignant
      potential of ESCC. MtDNA copy numbers of resected specimens from 80 patients
      treated with radical esophagectomy were measured by quantitative real-time PCR
      analyses. Human ESCC cells, TE8 and TE11, were cultured, and depletion of mtDNA
      content was induced by knockdown of mitochondrial transcription factor A
      expression or treatment with ethidium bromide. The mRNA and protein expression,
      proliferation, invasion, and cell cycle were investigated. The results showed
      that the mtDNA copy number of cancerous portions was 56.0 (37.4-234.5) percent
      that of non-cancerous parts and significantly lower (p<0.01). Low mtDNA copy
      number in resected cancerous tissues was significantly correlated with
      pathological depth of tumor invasion (p = 0.045) and pathological stage (p =
      0.025). Patients with lower mtDNA copy number had significantly poorer 5-year
      overall survival compared to patients with higher levels (p<0.01). The mtDNA
      depleted TE8 and TE11 cells had morphological changes and proliferated more
      slowly than control cells under normoxia but proliferated at almost the same rate
      under hypoxic conditions. In mtDNA-depleted cells, E-cadherin mRNA expression was
      decreased, and N-cadherin, vimentin, zeb-1, and cd44 mRNA expression was
      increased. Immunoblotting and flow cytometry analysis also showed downregulated E
      cadherin and upregulated N-cadherin and CD44 protein in mtDNA-depleted cells.
      Moreover, mtDNA-depleted cells had enhanced invasion, migration, and sphere
      formation abilities, and the cell cycle arrest at G0/G1 phase was induced in
      these cells. These results suggested that mtDNA-depleted ESCC cells had
      mesenchymal characteristics, cancer stemness, and tolerance to hypoxia, which
      played important role in cancer progression. In conclusion, a low copy number of
      mtDNA is associated with tumor progression in ESCC.

PMID- 29447306
TI  - Knotless Tape Suture Fixation of Quadriceps Tendon Rupture: A Novel Technique.
AB  - Quadriceps tendon ruptures disrupt the extensor mechanism of the knee and require
      urgent surgical management. Traditional repair techniques have had mixed
      biomechanical and clinical results risking weakness and extensor lag. We describe
      a novel technique using tape suture and knotless anchors, which has performed
      superiorly during biomechanical testing and yielded terrific early clinical
      results.

PMID- 29447307
TI  - Clinical and Histologic Evaluations of Immediately Placed SLA Dental Implants.
AB  - The goal of this investigation was to evaluate the bone-to-implant contact (BIC)
      of dental implants placed into fresh extraction sockets without pre-existing
      periapical pathology. When the extraction sites exhibited a gap distance of > 2
      mm, autogenous bone harvested from surrounding surgical sites was grafted to fill
      that gap with no barrier membranes. All implants were clinically stable and
      successful at 6 months postoperative. The histologic examination demonstrated an
      average of 66.2% BIC for all five immediately placed dental implants. The results
      of this study provided sufficient histologic and histomorphometric knowledge to
      support immediate dental implant placement in carefully selected clinical
      scenarios.

PMID- 29447308
TI  - Simplified Protocol for Relining Provisional Prosthesis on Natural Abutments: A
      Technical Note.
AB  - This article describes a simplified technique for relining provisional prostheses
      on natural abutments that can be applied to this specific type of tooth
      preparation with feather-edge finish line. Starting from a diagnostic wax-up, a
      provisional fixed restoration is constructed, containing all the correct
      structural information. This includes the controlled depth of the prosthetic
      margin into the gingival sulcus, the emergence profile, and the area from the
      emergence profile to the gingival third. Chair time is saved during the clinical
      procedures because the finishing and polishing steps are shortened, and the
      resulting provisional restoration is precise and highly biocompatible. This
      technique allows for a simple and quick relining and finishing procedure and for
      the delivery of an esthetic and biocompatible provisional restoration.

PMID- 29447309
TI  - Single-Tooth Replacement Using Dental Implants Supporting All-Ceramic and Metal
      Based Reconstructions: Results at 18 Months of Loading.
AB  - The aim of this study was to compare customized zirconia and titanium abutments
      with respect to survival rates and technical, biologic, and esthetic outcomes. A
      total of 28 patients with single implants were randomly assigned to 12 customized
      zirconia (test, AC) and 16 customized titanium (control, MC) abutments.
      Technical, biologic, and esthetic outcomes were assessed after a mean follow-up
      time of 18 months. No biologic complications were observed, and no statistical
      difference for the bone-to-implant distance was found at 18 months (AC -0.05 +/-
      0.51 mm vs MC -0.28 +/- 0.77 mm; P = .40). A similar discoloration of the peri
      implant mucosa was observed (DeltaEAC 9.6 +/- 5.4, DeltaEMC 7.6 +/- 5.3; P =
      .46). The mean papilla score values evaluation presented no statistically
      significant differences between the test and control groups (AC 2.07 +/- 0.94, MC
      1.96 +/- 0.84). At 18 months, reconstructions based on zirconia and titanium
      abutments exhibited similar survival rates and similar clinical outcomes.

PMID- 29447310
TI  - Retrospective Evaluation of Factors Related to the Outcomes of Regenerative
      Therapy for Implants Affected by Peri-implantitis.
AB  - The aim of this retrospective study was to examine the histories of 100 patients
      with 170 implants that were consecutively treated and reported in a previous
      study to identify which patient and implant factors might have affected the
      outcomes of therapy. Patient factors included history of periodontitis,
      hypertension, cardiac problems, rheumatoid arthritis, smoking, and penicillin
      allergy. Implant factors included whether the prosthesis was cemented or screw
      retained and initial bone loss (<= 50% or > 50% of implant length). Frequency of
      maintenance visits (<= 3 months or > 3 months) were recorded, as was patient age
      (<= 60 years or > 60 years). On the patient level, only postoperative maintenance
      (<= 3 months) showed a statistically significant effect on radiographic bone gain
      (RBG) compared to patients with > 3 months maintenance frequency. Nondiabetic
      patients showed a trend toward soft tissue gain. On an implant level, screw
      retained prostheses demonstrated a statistically significant RBG compared to
      those with cement-retained prostheses. Significant favorable differences were
      seen in all outcomes when evaluating presurgical bone level loss (> 50% of the
      implant length). Further studies with larger groups of patients are necessary to
      substantiate the findings in this report.

PMID- 29447311
TI  - A Simplified Approach for Restoration of Worn Dentition Using the Full Mock-up
      Concept: Clinical Case Reports.
AB  - Treatment of tooth wear has increased over the last two decades. However, the
      treatments involved have not been satisfactory to most patients, nor have they
      achieved the expected goal on some worn teeth. New approaches have emerged to
      reconstruct full arches in a minimally invasive way that take advantage of
      developments in the field of adhesive dentistry. These new concepts constitute a
      revolution in dentistry and their application requires adapted techniques and
      training. The purpose of this article is to suggest a precise and reproducible
      method that simplifies the treatment of worn dentition. A wax-up and a mock-up
      are primarily used to design the esthetic outcome and then used as a guide for
      the preparation of anterior teeth or the occlusal surfaces of posterior teeth.
      This not only provides the exact new vertical dimension of occlusion but serves
      as a guide for precisely controlling occlusal preparation simultaneously with
      buccal preparation. The classical cavity design for a partial bonded restoration
      on posterior worn dentition is also reviewed. The authors believe that during the
      preparation of the occlusal surfaces of the posterior teeth surfaces, the
      marginal ridges must be preserved to reduce the biologic cost and mechanical
      stress leading to fracture. A new type of thin and reduced restoration called
      tabletop is presented.

PMID- 29447312
TI  - The Bone Core Technique for the Augmentation of Limited Bony Defects: Five-Year
      Prospective Study with a New Minimally Invasive Technique.
AB  - The aim of this study was to evaluate a new minimally invasive surgical technique
      for the reconstruction of critical-size bony defect with local harvested bone
      core with simultaneous implant placement. In a prospective study, 186
      consecutively treated patients were included and controlled clinically and
      radiologically for at least 5 years postoperative. Every patient presented a bony
      defect affecting the buccal, lingual, or palatal wall. In all cases, the alveolar
      crest was wide enough to allow implant placement inside the bony contours. During
      implant bed preparation, a trephine bur (3.5 mm external diameter and 2.5 mm
      internal diameter) was used to harvest a bone core from the socket. After implant
      insertion, the buccal/palatal/lingual bony defect was grafted with bone chips
      covered with the bone core stabilized through compression with microscrews. After
      3 months of healing, the implants and the grafted bone were exposed and the width
      of the grafted area was measured. After prosthetic restoration, the patients were
      recalled regularly. A total of 223 grafted sites were documented. Minor primary
      healing complications were observed in 3 sites (1.4%), all in smoker patients,
      and were treated locally without any influence on the prognosis. All other sites
      healed uneventfully. In 19 cases (4.4%), exposure of the screw heads was detected
      1 to 3 months postoperatively without any inflammation or consequences for the
      grafted bone. The average width of the reconstructed area at the end of the
      grafting procedure was 2.4 +/- 0.8 mm, and at the reentry, 2.1 +/- 0.6 mm. There
      was a difference of remodeling between bone cores grafted totally inside or
      partially outside the bony contours. Bone cores grafted completely inside the
      bony contours demonstrated no resorption at 3 months postoperative, while bone
      cores grafted partially outside the bony contours in most cases showed partial
      resorption of the bone outside the bony contours. After 3 months of healing, all
      223 implants had achieved primary healing and osseointegration and were restored
      after an average time of 4 months. No implant failed during the control period.
      According to this study, the use of an autogenous bone core harvested during the
      implant bed preparation is a simple and safe method for the reconstruction of
      small bone defects.

PMID- 29447313
TI  - Double Duplicate Technique for CAD/CAM Full-Arch Immediate Loading: A Technical
      Description and Case Report.
AB  - Full-arch fixed implant-supported prostheses have shown high biologic success
      rates after long-term follow-up, along with technical and prosthetic
      complications. Adequate planning is necessary for immediate implant occlusal
      loading in a completely edentulous maxilla or mandible. For totally edentulous
      patients, the main prosthetic problem is the transfer of diagnostic information
      to the master cast when an immediate loading approach is used. The aim of this
      clinical case report is to illustrate a new prosthetic protocol for immediate
      implant loading in edentulous or potentially edentulous patients. This innovative
      procedure can successfully guide the clinician step by step in a predictable way
      from diagnosis to delivery of an immediately loaded implant-supported full-arch
      rehabilitation.

PMID- 29447314
TI  - Restoration of Periodontally Compromised Dentitions Using Telescopic Full-Arch
      Retrievable Prosthesis Supported by Tooth-Implant Combination: A Long-Term
      Retrospective Study.
AB  - Advanced periodontal disease is often associated with severe loss of tooth
      support, necessitating prosthetic rehabilitation to restore function and
      esthetics. For tooth-supported restorations, periodontally compromised teeth may
      need to be extracted due to early failure from functional overload. For
      tooth/implant-supported restorations, implants can be used to reduce the overload
      on teeth and to avoid tooth extraction, bone augmentation, or other risks
      associated with implant placement. The aim of this retrospective study was to
      evaluate the long-term outcomes of full-arch, retrievable, telescopic-retained
      prostheses (TRPs) on teeth and implants according to survival rate analyses and
      technical and biologic complications in full-mouth rehabilitation of
      periodontally compromised dentitions. A total of 18 periodontally compromised
      patients (7 women, 11 men) with a mean age of 46.8 years (SD: 6.3 years; range:
      32 to 64 years) were selected to receive supplementary implants with the aim of
      extensive prosthetic support in combined tooth/implant TRPs and annually
      evaluated for technical and/or biologic failures/complications. After a follow-up
      period of 15 years, all prostheses were in function. Complication rates were low,
      and maintenance services were limited to minor interventions. Combined
      tooth/implant TRPs improve prosthetic support and offer successful function over
      the long term in patients with periodontally compromised dentition.

PMID- 29447315
TI  - Failed Blade Implant After 25 Years in Function: Case Description and Histologic
      Analysis.
AB  - This report describes a failed blade implant after 25 years in function in the
      left maxilla and the results of histologic analysis of peri-implant tissues. The
      blade was retrieved, and histologic findings revealed that it was not
      osseointegrated despite being successfully in function for so many years. The
      long-term function of blade implants without osseointegration can be attributed
      to biotolerance exhibited by the implant rather than actual osseointegration.

PMID- 29447316
TI  - Peri-Implant Mucosal Creeping: Two Case Reports.
AB  - While creeping attachment in natural teeth has been reported in the literature
      for decades, the same phenomenon around dental implants is a new concept. This
      article describes two implant cases treated with free gingival autograft with
      follow-up at 18 and 30 months. Progressive coronal creeping of the mucosal margin
      was observed covering the implant and abutment surfaces postoperatively. This
      report demonstrates that mucosal creeping around implants may occur after peri
      implant plastic surgical procedures, further improving the final outcomes of
      therapy.

PMID- 29447317
TI  - Evaluation of Bone Stability and Esthetic Results After Immediate Implant
      Placement Using a Novel Synthetic Bone Substitute in the Anterior Zone: Results
      After 12 Months.
AB  - The aim of this study was to assess bone and soft tissue changes after tooth
      extraction and immediate implant insertion in the anterior maxilla. A novel
      synthetic bone graft (VivOss, Straumann) was used to fill the gap between the
      implant surface and the alveolar bone. Implants with a reduced diameter compared
      to the size of the socket were used. A fixed or removable provisional restoration
      was provided immediately after implant placement. Cone beam computed tomography
      (CBCT) scans were taken to evaluate bone changes, showing minor variations after
      12 months of follow-up. To evaluate soft tissue changes, clinical vertical
      measurements were performed. Based on the results obtained from 15 implants
      placed in 14 patients, it can be concluded that the use of an immediate implant
      in combination with a synthetic bone graft and immediate provisionalization seems
      to be a predictable treatment option with satisfactory esthetic results after 1
      year.

PMID- 29447318
TI  - Management of Multiple Gingival Recessions with the VISTA Technique: An 18-Month
      Clinical Case Series.
AB  - The purpose of the present study was to evaluate the efficacy of the vestibular
      incision subperiosteal tunnel access (VISTA) technique with collagen membrane,
      bioactive glass, and platelet-rich fibrin. A total of 22 systemically and
      periodontally healthy subjects with multiple gingival recession defects (Miller
      Class I and II) in the maxillary esthetic zone were enrolled in the study. The
      primary outcome measures were mean root coverage and alteration in gingival
      thickness. There were no surgical complications; however, one patient reported
      swelling of the upper lip area on the first postoperative day, which resolved
      spontaneously. A statistically significant increase in gingival thickness (0.45
      mm) and 94.17% +/- 8.42% mean root coverage was observed at 18 months. Within the
      limitations of this study, it was concluded that the VISTA technique augmented
      with collagen membrane, bioactive glass, and platelet-rich fibrin is a
      predictable modality in multiple recession management.

PMID- 29447319
TI  - Squamous Cell Carcinoma of the Gingiva Mimicking Periodontal Disease: A
      Diagnostic Challenge and Therapeutic Dilemma.
AB  - A case of squamous cell carcinoma of the gingiva (GSCC) in the left anterior
      maxilla in a 64-year-old woman that was treated for almost 5 years as suspected
      periodontal lesion prior to establishing the final diagnosis of oral cancer is
      presented in this case report. GSCCs have a variable clinical appearance, ranging
      from an exophytic mass to ulcerative lesions. They have been reported to pose a
      diagnostic challenge and are not infrequently initially misdiagnosed as
      periodontal disease. A delay in diagnosis and extraction of teeth in the vicinity
      of GSCCs has been demonstrated to increase the risk for lymph node metastasis and
      thus result in a lower 5-year survival rate. To avoid misdiagnosis and delay of
      the appropriate treatment, a proper histopathologic evaluation is mandatory
      whenever an incisional biopsy is performed. Furthermore, referral to a specialist
      in oral medicine or oral and maxillofacial surgery is indicated when a gingival
      lesion is nonresponsive to treatment, recurring, or rapidly growing in size.

PMID- 29447320
TI  - A Pilot Study on the Efficacy of a Treatment Algorithm to Detoxify Dental Implant
      Surfaces Affected by Peri-implantitis.
AB  - This in vitro pilot study was performed to determine whether a treatment
      algorithm including mechanical debridement, followed by air powder abrasion with
      glycine, followed by citric acid conditioning with vigorous flushing of the
      surface with sterile water after each step, is capable of decontaminating an
      infected implant surface. A total of 14 dental implants that were deemed hopeless
      due to advanced peri-implantitis were extracted. Of these, 6 implants served as
      tests and had their exposed surfaces treated with the decontamination protocol, 6
      served as untreated controls, and 2 were mechanically treated only, followed by
      rubbing the surface with sterile saline. All implants were placed in culture with
      human osteoprogenitor cells for 72 hours, and evaluation was performed using
      scanning electron microscopy. The 6 test implants all demonstrated attachment and
      proliferation of the normal human osteoprogenitor cells on their prior exposed
      and decontaminated surfaces. All of the untreated control and the mechanically
      debrided, sterile water-treated implants failed to demonstrate this same success.
      The results suggest that this protocol can decontaminate an implant surface
      affected by peri-implantitis. Further studies are warranted to determine if this
      technique would demonstrate similar success over a greater number of implants and
      whether this outcome may occur in humans.

PMID- 29447321
TI  - Decision Tree for Vertical Ridge Augmentation.
AB  - Vertical ridge augmentation (VRA) procedures before or during dental implant
      placement are technically challenging and often encounter procedure-related
      complications. To minimize complications and promote success, a literature search
      was conducted to validate procedures used for VRA. A decision tree based on the
      amount of additional ridge height needed (< 4, 4 to 6, or > 6 mm) was then
      developed to improve the procedure-selection process. At each junction, the
      clinician is urged to consider anatomical, clinical, and patient-related factors
      influencing treatment outcomes. This decision tree guides selection of the most
      appropriate treatment modality and sequence for safe, predictable management of
      the vertically deficient ridge in implant therapy.

PMID- 29447322
TI  - Fixed Conometric Retention with CAD/CAM Conic Coupling Abutments and
      Prefabricated Syncone Caps: A Case Series.
AB  - The conometric retention system was proposed and described as a predictable
      alternative to retain fixed implant-supported complete dentures and, more
      recently, to retain fixed partial restorations. Currently available studies
      describe a technique based on the Ankylos (Dentsply) implant system and stock
      conic coupling abutments. The purpose of this case series study is therefore to
      demonstrate the possibility of using Atlantis computer-aided design/computer
      assisted manufacture technology to produce Conus abutments (Dentsply) and using
      the fixed conometric retention with other implant brands for which appropriate
      stock conic coupling abutments are not available.

PMID- 29447323
TI  - Clinically Oriented Patient Maintenance Protocol: A Clinical Consensus of
      Experts.
AB  - The aim of the present survey was to define the most appropriate recall regimen
      and professional maintenance care protocol, identifying the main relative issues,
      based on a consensus of experts with long-term clinical experience. The survey
      consisted of 14 clinically relevant focused questions. The answers of each expert
      were aggregated to formulate clinical recommendations. The maintenance care
      protocol must be individually determined and a baseline condition identified. The
      recall frequency must have a specific periodicity, and bone levels must be
      radiographically checked at least every 2 years, unless specific needs require a
      shorter interval.

PMID- 29447324
TI  - Accuracy and Usefulness of CBCT in Periodontology: A Systematic Review of the
      Literature.
AB  - A systematic literature review was performed regarding the accuracy and
      usefulness of cone beam computed tomography (CBCT) in the field of
      periodontology. A total of 580 articles were identified, of which 13 met the
      inclusion criteria. Results showed a high accuracy of CBCT in visualizing
      periodontal structures and the demonstrated the usefulness of CBCT in
      regenerative periodontal surgery of maxillary molars. It remains questionable
      whether this gain of additional information actually leads to a better clinical
      outcome in periodontal treatment. Currently, the use of CBCT in periodontology
      should be restricted to complex periodontal cases, particularly those involving
      maxillary molars.

PMID- 29447325
TI  - Long-term results after restoring nasal tip support using auricular cartilage as
      an intercrural columellar strut graft: the "I-Beam" technique.
AB  - BACKGROUND: The lack of nasal tip support resulting in poor protection and
      projection of the nose is a common cause of nasal obstruction and cosmetic
      impairment. Although septal cartilage is preferred for restoration of nasal tip
      support, there is often not enough septal cartilage available. We describe an
      intercrural columellar strut graft in a circumferential soft tissue pocket: the I
      Beam technique. METHODOLOGY: In this cohort study over an 8-year period the
      clinical and biometrical long-term results after restoration of nasal tip support
      with an autologous auricular cartilage graft, the I-Beam technique, is evaluated.
      RESULTS: Out of the 72 consecutive septorhinoplasties with the I-Beam technique,
      we studied 66 patients in the median long-term follow-up of 89 months. In all
      patients a significant improvement in nasal tip projection was found. A
      functional improvement in nasal breathing was achieved in 86%. The overall
      satisfaction with the I-Beam graft was of 83%. No deterioration in smell
      perception was found after surgery. CONCLUSIONS: The I-Beam technique using back
      to-back sutured autologous auricular cartilage is a safe and effective technique
      and gives long-term structural support and enhances tip projection.

PMID- 29447326
TI  - Prospective study on the outcome of the sphenoid drill out procedure.
AB  - BACKGROUND: Chronic sphenoid sinusitis refractory to both medical therapy and
      sphenoidotomy requires a more extended intervention based on the principles of
      salvage surgery. Our aim is to describe the sphenoid drill out technique as a
      sphenoid salvage intervention and to outline its implications on clinical outcome
      and quality of life. METHODOLOGY: 12 patients with chronic sphenoiditis
      undergoing a sphenoid drill out procedure were examined by nasal endoscopy
      preoperatively and postoperatively for one year. Preoperative and postoperative
      quality of life questionnaires (RSOM-31 and SF-36) were obtained. RESULTS: All
      but one patient had a completely patent neostium without scar formation. No major
      complications occurred after this procedure. All patients reported at least an
      improvement of their symptoms, 50% of patients were even symptom free at one year
      after surgery. The median postoperative RSOM-31 score was significantly lower
      than the preoperative score. Both the physical component summary (PCS) and the
      mental component summary (MCS) of the SF-36 score improved significantly. None of
      the patients needed a revision procedure. CONCLUSION: Sphenoid drill out is a
      safe and effective technique with a high success rate. In patients with chronic
      sphenoid sinusitis refractory to medical therapy and surgery it could be a valid
      alternative to revision sphenoidotomy.

PMID- 29447327
TI  - ?
AB  - BACKGROUND: The lack of nasal tip support resulting in poor protection and
      projection of the nose is a common cause of nasal obstruction and cosmetic
      impairment. Although septal cartilage is preferred for restoration of nasal tip
      support, there is often not enough septal cartilage available. We describe an
      intercrural columellar strut graft in a circumferential soft tissue pocket: the I
      Beam technique. METHODOLOGY: In this cohort study over an 8-year period the
      clinical and biometrical long-term results after restoration of nasal tip support
      with an autologous auricular cartilage graft, the I-Beam technique, is evaluated.
      RESULTS: Out of the 72 consecutive septorhinoplasties with the I-Beam technique,
      we studied 66 patients in the median long-term follow-up of 89 months. In all
      patients a significant improvement in nasal tip projection was found. A
      functional improvement in nasal breathing was achieved in 86%. The overall
      satisfaction with the I-Beam graft was of 83%. No deterioration in smell
      perception was found after surgery. CONCLUSIONS: The I-Beam technique using back
      to-back sutured autologous auricular cartilage is a safe and effective technique
      and gives long-term structural support and enhances tip projection.

PMID- 29447328
TI  - Cardiac surgery in adult patients with remitted or active malignancies: a review
      of preoperative screening, surgical management and short- and long-term
      postoperative results.
AB  - Candidate patients for cardiac surgery procedures with a history of malignancies
      and antitumour therapy or with an active cancer and on antineoplastic treatment
      are increasingly common in daily practice. Oncological therapy can lead to
      cardiovascular injury and, therefore, has the potential for impacting operative
      risks and surgical strategies. This means that a number of considerations are
      essential to take into account prior to cardiac surgery. These include the type
      of cancer, previous cardiotoxicity or concomitant antitumour therapy,
      reversibility or irreversibility of such complications, the interaction between
      cancer disease course and extracorporeal circulation, the need for associated
      surgery and the impact of cancer on early and long-term outcomes. Adequate
      preoperative evaluation of cardiovascular abnormalities potentially related to
      antineoplastic therapy and proper diagnostic workup of other conditions linked to
      the type of cancer (e.g. haematological disorders and lung dysfunction) are
      therefore of paramount importance for appropriate surgical decision-making.
      Careful evaluation of the association of cardiovascular disease to be treated and
      the prognosis of remitted or active cancer should be established to enhance the
      prediction of early, medium and long-term outcomes and for a more correctly
      informed patient. Furthermore, if the prognosis of operated patients appears
      unfavourable, then alternative therapeutic strategies can be applied without
      significant delay. The aim of this review is to give an overview of factors that
      should be considered in adult patients who are undergoing, or have undergone,
      treatment for oncological indications who are candidates for cardiac surgery.

PMID- 29447329
TI  - Randomised phase III trial of vinflunine plus capecitabine versus capecitabine
      alone in patients with advanced breast cancer previously treated with an
      anthracycline and resistant to taxane.
AB  - Background: Capecitabine is an approved standard therapy for anthracycline- and
      taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine
      has demonstrated single-agent activity in phase II studies in this setting and
      activity and tolerability when combined with capecitabine. We compared the
      combination of vinflunine plus capecitabine (VC) with single-agent capecitabine.
      Patients and methods: Patients with locally recurrent/metastatic BC previously
      treated or resistant to an anthracycline and resistant to taxane therapy were
      randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine
      [825 mg/m2 twice daily (b.i.d.), days 1-14] every 3 weeks (q3w) or single-agent
      oral capecitabine (1250 mg/m2 b.i.d., days 1-14) q3w. The primary end point was
      progression-free survival (PFS) assessed by an independent review committee. The
      study had 90% power to detect a 30% improvement in PFS. Results: Overall, 770
      patients were randomised. PFS was significantly longer with VC than with
      capecitabine alone [hazard ratio, 0.84, 95% confidence interval (CI), 0.71-0.99;
      log-rank P = 0.043; median 5.6 versus 4.3 months, respectively]. Median overall
      survival was 13.9 versus 11.7 months with VC versus capecitabine alone,
      respectively (hazard ratio, 0.98; 95% CI, 0.83-1.15; log-rank P = 0.77). No
      difference in quality of life was observed between the two treatment arms. The
      most common adverse events (NCI CTCAE version 3.0) in the combination arm were
      haematological and gastrointestinal. Grade 4 neutropenia was more frequent with
      VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2%
      versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3:
      4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both
      arms (grade 3: 1% versus 0.3%). Conclusions: Vinflunine combined with
      capecitabine demonstrated a modest improvement in PFS and an acceptable safety
      profile compared with capecitabine alone in patients with anthracycline- and
      taxane-pretreated locally recurrent/metastatic BC. ClinicalTrials.gov:
      NCT01095003.

PMID- 29447330
TI  - Is central lung tumour location really predictive for occult mediastinal nodal
      disease in (suspected) non-small-cell lung cancer staged cN0 on 18F
      fluorodeoxyglucose positron emission tomography-computed tomography?
AB  - OBJECTIVES: Current guidelines recommend preoperative invasive mediastinal
      staging in centrally located tumours with negative mediastinum on positron
      emission tomography-computed tomography, based on a 20-30% prevalence of occult
      mediastinal disease (pN2-3). However, a uniform definition of central tumour
      location is lacking. Our objective was to determine the best definition in
      predicting occult pN2-3. METHODS: A single-institution database was queried for
      patients with (suspected) non-small-cell lung cancer staged cN0 after positron
      emission tomography-computed tomography and referred to invasive staging and/or
      primary surgery. We evaluated 5 definitions: inner 1/3, inner 2/3, contact with
      bronchovascular structures, <=2 cm from bronchus or endobronchial visualization.
      RESULTS: Between 2005 and 2015, 813 patients were eligible (cT1: 42%, cT2: 28%,
      cT3: 17% and cT4: 11%). Invasive mediastinal staging and resection were performed
      in 30% and 97% of patients, respectively. Any nodal upstaging (pN+) was found in
      21% of patients, of whom pN2-3 was found in 8%. Central tumour location
      demonstrated 4 times higher odds for any pN+ [for inner 1/3 vs outer 2/3, odds
      ratio 3.90 (95% confidence interval 2.24-6.77), P < 0.001], whereas no
      significantly different odds was observed for pN2-3. The discriminative ability
      for pN+ was not significantly different between the several definitions.
      CONCLUSIONS: The prevalence of occult pN2-3 was only 8% when modern fusion
      positron emission tomography-computed tomography imaging pointed at clinical N0
      non-small-cell lung cancer. None of the 5 verified definitions of centrality was
      predictive for occult pN2-3. However, each definition of centrality was related
      to any pN+ at a prevalence of 21%, without significant differences in
      discriminative ability between definitions. These data question whether
      indication for preoperative invasive mediastinal staging should be based on
      centrality alone.

PMID- 29447331
TI  - Evaluation of coronary artery disease after computed tomography angiography.

PMID- 29447332
TI  - The impact of the maternal-foetal environment on outcomes of surgery for
      congenital heart disease in neonates.
AB  - OBJECTIVES: Pregnancies with congenital heart disease in the foetus have an
      increased prevalence of pre-eclampsia, small for gestational age and preterm
      birth, which are evidence of an impaired maternal-foetal environment (MFE).
      METHODS: The impact of an impaired MFE, defined as pre-eclampsia, small for
      gestational age or preterm birth, on outcomes after cardiac surgery was evaluated
      in neonates (n = 135) enrolled in a study evaluating exposure to environmental
      toxicants and neuro-developmental outcomes. RESULTS: The most common diagnoses
      were transposition of the great arteries (n = 47) and hypoplastic left heart
      syndrome (n = 43). Impaired MFE was present in 28 of 135 (21%) subjects, with
      small for gestational age present in 17 (61%) patients. The presence of an
      impaired MFE was similar for all diagnoses, except transposition of the great
      arteries (P < 0.006). Postoperative length of stay was shorter for subjects
      without an impaired MFE (14 vs 38 days, P < 0.001). Hospital mortality was not
      significantly different with or without impaired MFE (11.7% vs 2.8%, P = 0.104).
      However, for the entire cohort, survival at 36 months was greater for those
      without an impaired MFE (96% vs 68%, P = 0.001). For patients with hypoplastic
      left heart syndrome, survival was also greater for those without an impaired MFE
      (90% vs 43%, P = 0.007). CONCLUSIONS: An impaired MFE is common in pregnancies in
      which the foetus has congenital heart disease. After cardiac surgery in neonates,
      the presence of an impaired MFE was associated with lower survival at 36 months
      of age for the entire cohort and for the subgroup with hypoplastic left heart
      syndrome.

PMID- 29447333
TI  - Corrigendum: Alcohol Use in Adolescence and Later Working Memory: Findings From a
      Large Population-Based Birth Cohort.

PMID- 29447334
TI  - The ideal use of dogs in medicine.

PMID- 29447337
TI  - An analysis of patients requiring unifocalization revision following midline
      unifocalization for pulmonary atresia with ventricular septal defect and major
      aortopulmonary collaterals.
AB  - OBJECTIVES: Midline unifocalization has been developed for the surgical treatment
      of pulmonary atresia with ventricular septal defect and major aortopulmonary
      collateral arteries. All patients will eventually require reoperation because of
      the presence of a conduit, and some patients may also require revision of the
      distal unifocalized bed. The purpose of this study was to analyse the need for
      unifocalization revision following midline unifocalization. METHODS: This was a
      retrospective review of 241 patients who underwent midline unifocalization for
      the treatment of pulmonary atresia with ventricular septal defect and major
      aortopulmonary collateral arteries. Two hundred and four (85.4%) patients had a
      single-stage complete repair, whereas 37 patients had a unifocalization and
      placement of a central shunt. Seventy-eight patients have subsequently undergone
      reoperations at our institution, including 44 operations that required
      unifocalization revision. These 44 patients were compared with the 191 operative
      survivors who did not require revision. RESULTS: An analysis of risk factors for
      requiring unifocalization revision included the following: (i) single-stage
      complete repair versus unifocalization and shunt (14.7% vs 37.8%, P < 0.001),
      (ii) right ventricle to aortic pressure ratio at the initial repair (0.33 +/-
      0.07 vs 0.44 +/- 0.08, P < 0.001) and (iii) absence of central pulmonary arteries
      (32.8% vs 13.4%, P < 0.001). CONCLUSIONS: Data demonstrate that 44 of 241 (18%)
      patients who underwent midline unifocalization have subsequently required
      revision of their unifocalization. The need for unifocalization revision was
      associated with 3 factors, all of which were known at the time of discharge from
      the initial unifocalization. These data suggest that potentially higher risk
      patients should be monitored more closely than their lower risk counterparts.

PMID- 29447335
TI  - Condition-dependent generation of aquaporin-4 antibodies from circulating B cells
      in neuromyelitis optica.
AB  - Autoantibodies to aquaporin-4 (AQP4) are pathogenic in neuromyelitis optica
      spectrum disorder (NMOSD). However, it is not known which B cells are the major
      contributors to circulating AQP4 antibodies nor which conditions promote their
      generation. Our experiments showed CD19+CD27++CD38++ circulating ex vivo antibody
      secreting cells did not produce AQP4 antibodies under several culture conditions.
      To question whether other cells in circulation were capable of AQP4 antibody
      production, B cells were differentiated into antibody-secreting cells in vitro.
      Unfractionated peripheral blood mononuclear cells, isolated from 12 patients with
      NMOSD and a wide range of serum AQP4 antibody levels (91-26 610 units), were
      cultured with factors that mimicked established associations of NMOSD including T
      cell help, concurrent infections and cytokines reported to be elevated in NMOSD.
      Overall, the in vitro generation of CD19+CD27++CD38++ cells across several
      culture conditions correlated closely with the total IgG secreted (P < 0.0001, r
      = 0.71), but not the amount of AQP4 antibody. AQP4 antibody production was
      enhanced by CD40-ligand (P = 0.005), and by interleukin-2 plus toll-like receptor
      stimulation versus interleukin-21-predominant conditions (P < 0.0001), and did
      not require antigen. Across NMOSD patients, this in vitro generation of AQP4
      antibodies correlated well with serum AQP4 antibody levels (P = 0.0023, r =
      0.81). To understand how early within B cell lineages this AQP4 specificity was
      generated, purified B cell subsets were activated under these optimized
      conditions. Naive pre-germinal centre B cells (CD19+CD27-IgD+) differentiated to
      secrete AQP4 antibodies as frequently as post-germinal centre cells (CD19+CD27+).
      Taken together, these human cell-culture experiments demonstrate that preformed B
      cells, rather than ex vivo circulating antibody-secreting cells, possess AQP4
      reactivity. Their differentiation and AQP4 antibody secretion is preferentially
      driven by select cytokines and these cells may make the dominant contribution to
      serum AQP4 antibodies. Furthermore, as AQP4-specific B cells can derive from
      likely autoreactive naive populations an early, pre-germinal centre loss of
      immunological tolerance appears present in some patients with NMOSD. This study
      has implications for understanding mechanisms of disease perpetuation and for
      rational choice of immunotherapies in NMOSD. Furthermore, the in vitro model
      presents an opportunity to apply condition-specific approaches to patients with
      NMOSD and may be a paradigm to study other antibody-mediated
      diseases.awy010media15732448284001.

PMID- 29447338
TI  - Exposure-Lag-Response in Longitudinal Studies: Application of Distributed-Lag
      Nonlinear Models in an Occupational Cohort.
AB  - Prolonged exposures can have complex relationships with health outcomes, as
      timing, duration, and intensity of exposure are all potentially relevant. Summary
      measures such as cumulative exposure or average intensity of exposure may not
      fully capture these relationships. We applied penalized and unpenalized
      distributed-lag nonlinear models (DLNMs) with flexible exposure-response and lag
      response functions in order to examine the association between crystalline silica
      exposure and mortality from lung cancer and nonmalignant respiratory disease in a
      cohort study of 2,342 California diatomaceous earth workers followed during 1942
      2011. We also assessed associations using simple measures of cumulative exposure
      assuming linear exposure-response and constant lag-response. Measures of
      association from DLNMs were generally higher than those from simpler models. Rate
      ratios from penalized DLNMs corresponding to average daily exposures of 0.4 mg/m3
      during lag years 31-50 prior to the age of observed cases were 1.47 (95%
      confidence interval (CI): 0.92, 2.35) for lung cancer mortality and 1.80 (95% CI:
      1.14, 2.85) for nonmalignant respiratory disease mortality. Rate ratios from the
      simpler models for the same exposure scenario were 1.15 (95% CI: 0.89, 1.48) and
      1.23 (95% CI: 1.03, 1.46), respectively. Longitudinal cohort studies of prolonged
      exposures and chronic health outcomes should explore methods allowing for
      flexibility and nonlinearities in the exposure-lag-response.

PMID- 29447340
TI  - Dysfunction of DNA damage-inducible transcript 4 in the decidua is relevant to
      the pathogenesis of preeclampsia.
AB  - Preeclampsia (PE) is a pregnancy-related disorder that occurs after 20 weeks of
      gestation and affects 3-5% of all human pregnancies worldwide. However, the
      pathogenesis of PE still remains poorly understood. A deficiency in
      decidualization is considered a contributing factor to the development of PE. The
      DNA damage inducible transcript 4 (DDIT4) gene encodes a protein whose main
      function is inhibiting mammalian target of rapamycin (mTOR) under stress, and
      several studies have demonstrated that its expression promotes tumor cell
      apoptosis. Our previous RNA-Seq results showed that DDIT4 is significantly
      decreased in the decidua of PE women. Here, we aimed to define the role of DDIT4
      in human decidualization and its relationship with PE. The results indicated that
      DDIT4 was markedly decreased in the decidua of severe PE compared with those from
      uncomplicated pregnancies. The expression of DDIT4 in human endometrial stromal
      cell (hESC) line and primary hESCs was up-regulated during decidualization.
      Knockdown DDIT4 in hESCs and primary hESCs caused a significant reduction in the
      transcription of decidualization markers, insulin-like growth factor binding
      protein 1 (IGFBP1) and prolactin (PRL). In addition, silencing DDIT4 caused up
      regulated p-mTOR and p-p70s6k and reduced apoptosis, whereas rapamycin, an
      inhibitor of mTOR, reversed the result of apoptosis. Moreover, the expression of
      cleaved-caspase 3 in severe PE was significantly lower than that of uncomplicated
      pregnancies, which was unfavorable for trophoblast invasion. Our data suggest
      that DDIT4 is critical for normal decidualization and the apoptosis of decidual
      cells. DDIT4 deficiency is likely involved in the development of PE.

PMID- 29447339
TI  - Integrated microRNA and mRNA network analysis of the human myometrial
      transcriptome in the transition from quiescence to labor.
AB  - We conducted integrated transcriptomics network analyses of miRNA and mRNA
      interactions in human myometrium to identify novel molecular candidates
      potentially involved in human parturition. Myometrial biopsies were collected
      from women undergoing primary Cesarean deliveries in well-characterized clinical
      scenarios: (1) spontaneous term labor (TL, n = 5); (2) term nonlabor (TNL, n =
      5); (3) spontaneous preterm birth (PTB) with histologic chorioamnionitis (PTB
      HCA, n = 5); and (4) indicated PTB nonlabor (PTB-NL, n = 5). RNAs were profiled
      using RNA sequencing, and miRNA-target interaction networks were mined for key
      discriminatory subnetworks. Forty miRNAs differed between TL and TNL myometrium,
      while seven miRNAs differed between PTB-HCA vs. PTB-NL specimens; six of these
      were cross-validated using quantitative PCR. Based on the combined sequencing
      data, unsupervised clustering revealed two nonoverlapping cohorts that differed
      primarily by absence or presence of uterine quiescence, rather than gestational
      age or original clinical cohort. The intersection of differentially expressed
      miRNAs and their targets predicted 22 subnetworks with enriched representation of
      miR-146b-5p, miR-223-3p, and miR-150-5p among miRNAs, and of myocyte enhancer
      factor-2C (MEF2C) among mRNAs. Of four known MEF2 transcription factors,
      decreased MEF2A and MEF2C expression in women with uterine nonquiescence was
      observed in the sequencing data, and validated in a second cohort by quantitative
      PCR. Immunohistochemistry localized MEF2A and MEF2C to myometrial smooth muscle
      cells and confirmed decreased abundance with labor. Collectively, these results
      suggest altered MEF2 expression may represent a previously unrecognized process
      through which miRNAs contribute to the phenotypic switch from quiescence to labor
      in human myometrium.

PMID- 29447341
TI  - ChemDistiller: an engine for metabolite annotation in mass spectrometry.
AB  - Motivation: High-resolution mass spectrometry permits simultaneous detection of
      thousands of different metabolites in biological samples; however, their
      automated annotation still presents a challenge due to the limited number of
      tailored computational solutions freely available to the scientific community.
      Results: Here, we introduce ChemDistiller, a customizable engine that combines
      automated large-scale annotation of metabolites using tandem MS data with a
      compiled database containing tens of millions of compounds with pre-calculated
      'fingerprints' and fragmentation patterns. Our tests using publicly and
      commercially available tandem MS spectra for reference compounds show retrievals
      rates comparable to or exceeding the ones obtainable by the current state-of-the
      art solutions in the field while offering higher throughput, scalability and
      processing speed. Availability and implementation: Source code freely available
      for download at https://bitbucket.org/iAnalytica/chemdistillerpython.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29447342
TI  - Diagnosing coronary artery disease after a positive coronary computed tomography
      angiography: the Dan-NICAD open label, parallel, head to head, randomized
      controlled diagnostic accuracy trial of cardiovascular magnetic resonance and
      myocardial perfusion scintigraphy.
AB  - Aims: Perfusion scans after coronary computed tomography angiography (CCTA) in
      patients with suspected coronary artery disease (CAD) may reduce unnecessary
      invasive coronary angiographies (ICAs). However, the diagnostic accuracy of
      perfusion scans after primary CCTA is unknown. The aim of this study was to
      determine the diagnostic accuracy of cardiac magnetic resonance (CMR) and
      myocardial perfusion scintigraphy (MPS) against ICA with fractional flow reserve
      (FFR) in patients suspected of CAD by CCTA. Methods and results: Included were
      consecutive patients (1675) referred to CCTA with symptoms of CAD and
      low/intermediate risk profile. Patients with suspected CAD based on CCTA were
      randomized 1:1 to CMR or MPS followed by ICA with FFR. Obstructive CAD was
      defined as FFR <= 0.80 or > 90% diameter stenosis by visual assessment. After
      initial CCTA, 392 patients (23%) were randomized; 197 to CMR and 195 to MPS.
      Perfusion scans and ICA were completed in 292 patients (CMR 148, MPS 144). Based
      on the ICA, 117/292 (40%) patients were classified with CAD. Sensitivity,
      specificity, negative predictive value (NPV), and positive predictive value (PPV)
      for CMR were 41%, 95% CI [28-54], 84% [75-91], 62% [45-78], and 68% [58-76],
      respectively. For the MPS group 36% [24-50], 94% [87-98], 81% [61-93], and 68%
      [59-76], respectively. Conclusion: Patients with low/intermediate CAD risk and a
      positive CCTA scan represent a challenge to perfusion techniques indicated by the
      low sensitivity of both CMR and MPS with FFR as a reference. The mechanisms
      underlying this discrepancy need further investigation.

PMID- 29447343
TI  - Reply to Rescigno et al.

PMID- 29447344
TI  - The balance between short-term and long-term outcomes of bilateral internal
      thoracic artery skeletonization in coronary artery bypass surgery: a propensity
      matched cohort study.
AB  - OBJECTIVES: There is growing interest in the use of bilateral internal thoracic
      arteries (BITAs) for myocardial revascularization. This study sought to compare
      the balance between early benefits and long-term outcomes of skeletonized or non
      skeletonized conduits and to determine whether differences in outcomes are
      affected by other patient risk factors. METHODS: BITAs were used in 1504 cases
      with either SK or NSK conduits. Propensity matching was completed using 22
      covariates identifying 441 pairs of patients. The primary outcomes are the
      sternal wound infection in the short term and the composite outcome of all-cause
      mortality, myocardial infarction, revascularization and congestive heart failure.
      Outcomes were assessed using paired analysis techniques and Cox proportional
      hazards regression models stratified using the matched pairs. RESULTS: Incidences
      of in-hospital mortality and perioperative myocardial infarction were similar in
      both groups. There were fewer sternal wound infections in the SK group (5.4 vs
      9.1%, P = 0.033). Homogeneity testing of the relative risk estimates confirmed
      that there was a protective effect of skeletonization in men that was not
      demonstrated in women (P = 0.020). SK had a protective effect in diabetics not
      seen in non-diabetics (P = 0.048). The composite outcome of all-cause mortality,
      myocardial infarction, revascularization and congestive heart failure at a median
      of 5.6 years was comparable in both groups (hazard ratio 0.81, 95% confidence
      interval 0.57-1.15). CONCLUSION: Skeletonization results in better perioperative
      outcomes and comparable cardiac outcomes in patients undergoing BITA with the
      greatest benefit in men and patients with chronic obstructive pulmonary disease.

PMID- 29447345
TI  - The BioCyc collection of microbial genomes and metabolic pathways.
AB  - BioCyc.org is a microbial genome Web portal that combines thousands of genomes
      with additional information inferred by computer programs, imported from other
      databases and curated from the biomedical literature by biologist curators.
      BioCyc also provides an extensive range of query tools, visualization services
      and analysis software. Recent advances in BioCyc include an expansion in the
      content of BioCyc in terms of both the number of genomes and the types of
      information available for each genome; an expansion in the amount of curated
      content within BioCyc; and new developments in the BioCyc software tools
      including redesigned gene/protein pages and metabolite pages; new search tools; a
      new sequence-alignment tool; a new tool for visualizing groups of related
      metabolic pathways; and a facility called SmartTables, which enables biologists
      to perform analyses that previously would have required a programmer's
      assistance.

PMID- 29447346
TI  - Penalized estimation of complex, non-linear exposure-lag-response associations.
AB  - We propose a novel approach for the flexible modeling of complex exposure-lag
      response associations in time-to-event data, where multiple past exposures within
      a defined time window are cumulatively associated with the hazard. Our method
      allows for the estimation of a wide variety of effects, including potentially
      smooth and smoothly time-varying effects as well as cumulative effects with leads
      and lags, taking advantage of the inference methods that have recently been
      developed for generalized additive mixed models. We apply our method to data from
      a large observational study of intensive care patients in order to analyze the
      association of both the timing and the amount of artificial nutrition with the
      short term survival of critically ill patients. We evaluate the properties of the
      proposed method by performing extensive simulation studies and provide a
      systematic comparison with related approaches.

PMID- 29447347
TI  - Cultural adaptation of an evidence-based lifestyle intervention for diabetes
      prevention in Chinese women at risk for diabetes: results of a randomized trial.
AB  - Background: The prevalence of both obesity and type 2 diabetes has been on the
      rise in China. This randomized controlled trial was conducted to test the
      feasibility and effectiveness of an evidence-based diabetes prevention program in
      Yuci, Shanxi Province, China from 2012 to 2014. Methods: Women with pre-diabetes,
      ages 25-65 y, were assigned randomly to a comparison (n=75) or 6-mo lifestyle
      intervention condition (n=109). Weight, fasting glucose, hemoglobin A1c and self
      reported diet and physical activity were measured at baseline, 6 mo and 12 mo.
      Results: All measures except fasting glucose improved favorably in both
      comparison and intervention participants at the 6- and 12-mo follow-ups.
      Participants in the intervention group lost more weight (-0.91 kg, p<0.05) and
      had a lower body mass index (-0.39 kg/m2, p<0.05) than the comparison group at
      follow-up. A total of 31.6% (31/98) and 16.2% (11/68) of the participants in the
      intervention and comparison groups, respectively, achieved the weight loss goal
      of 5% at follow-up. There was no significant group difference in outcome measures
      at the 12-mo follow-up. Participants in the intervention group also showed
      favorable changes in self-reported diet and physical activity measures.
      Conclusions: A lifestyle intervention to prevent diabetes in at-risk women in
      community health centers in China is feasible and acceptable but effect sizes
      were small.

PMID- 29447349
TI  - Aging: the next cardiovascular disease?

PMID- 29447348
TI  - Transcriptome analysis reveals intermittent fasting-induced genetic changes in
      ischemic stroke.
AB  - Genetic changes due to dietary intervention in the form of either calorie
      restriction (CR) or intermittent fasting (IF) are not reported in detail until
      now. However, it is well established that both CR and IF extend the lifespan and
      protect against neurodegenerative diseases and stroke. The current research aims
      were first to describe the transcriptomic changes in brains of IF mice and,
      second, to determine whether IF induces extensive transcriptomic changes
      following ischemic stroke to protect the brain from injury. Mice were randomly
      assigned to ad libitum feeding (AL), 12 (IF12) or 16 (IF16) h daily fasting. Each
      diet group was then subjected to sham surgery or middle cerebral artery occlusion
      and consecutive reperfusion. Mid-coronal sections of ipsilateral cerebral tissue
      were harvested at the end of the 1 h ischemic period or at 3, 12, 24 or 72 h of
      reperfusion, and genome-wide mRNA expression was quantified by RNA sequencing.
      The cerebral transcriptome of mice in AL group exhibited robust, sustained up
      regulation of detrimental genetic pathways under ischemic stroke, but activation
      of these pathways was suppressed in IF16 group. Interestingly, the cerebral
      transcriptome of AL mice was largely unchanged during the 1 h of ischemia,
      whereas mice in IF16 group exhibited extensive up-regulation of genetic pathways
      involved in neuroplasticity and down-regulation of protein synthesis. Our data
      provide a genetic molecular framework for understanding how IF protects brain
      cells against damage caused by ischemic stroke, and reveal cellular signaling and
      bioenergetic pathways to target in the development of clinical interventions.

PMID- 29447350
TI  - Soil protists: a fertile frontier in soil biology research.
AB  - Protists include all eukaryotes except plants, fungi and animals. They are an
      essential, yet often forgotten, component of the soil microbiome. Method
      developments have now furthered our understanding of the real taxonomic and
      functional diversity of soil protists. They occupy key roles in microbial
      foodwebs as consumers of bacteria, fungi and other small eukaryotes. As parasites
      of plants, animals and even of larger protists, they regulate populations and
      shape communities. Pathogenic forms play a major role in public health issues as
      human parasites, or act as agricultural pests. Predatory soil protists release
      nutrients enhancing plant growth. Soil protists are of key importance for our
      understanding of eukaryotic evolution and microbial biogeography. Soil protists
      are also useful in applied research as bioindicators of soil quality, as models
      in ecotoxicology and as potential biofertilizers and biocontrol agents. In this
      review, we provide an overview of the enormous morphological, taxonomical and
      functional diversity of soil protists, and discuss current challenges and
      opportunities in soil protistology. Research in soil biology would clearly
      benefit from incorporating more protistology alongside the study of bacteria,
      fungi and animals.

PMID- 29447351
TI  - Research versus practice in quality improvement? Understanding how we can bridge
      the gap.
AB  - The gap between implementers and researchers of quality improvement (QI) has
      hampered the degree and speed of change needed to reduce avoidable suffering and
      harm in health care. Underlying causes of this gap include differences in goals
      and incentives, preferred methodologies, level and types of evidence prioritized
      and targeted audiences. The Salzburg Global Seminar on 'Better Health Care: How
      do we learn about improvement?' brought together researchers, policy makers,
      funders, implementers, evaluators from low-, middle- and high-income countries to
      explore how to increase the impact of QI. In this paper, we describe some of the
      reasons for this gap and offer suggestions to better bridge the chasm between
      researchers and implementers. Effectively bridging this gap can increase the
      generalizability of QI interventions, accelerate the spread of effective
      approaches while also strengthening the local work of implementers. Increasing
      the effectiveness of research and work in the field will support the knowledge
      translation needed to achieve quality Universal Health Coverage and the
      Sustainable Development Goals.

PMID- 29447352
TI  - Improvement of emergency department patient flow using lean thinking.
AB  - Objective: To apply lean thinking in triage acuity level-3 patients in order to
      improve emergency department (ED) throughtput and waiting time. Design: A
      prospective interventional study. Setting: An ED of a tertiary care hospital.
      Participants: Triage acuity level-3 patients. Intervention(s): To apply lean
      techniques such as value stream mapping, workplace organization, reduction of
      wastes and standardization by the frontline staff. Main Outcome Measure(s): Two
      periods were compared: (i) pre-lean: April-September, 2015; and (ii) post-lean:
      April-September, 2016. Variables included: median process time (time from
      beginning of nurse preparation to the end of nurse finalization after doctor
      disposition) of both discharged and transferred to observation patients; median
      length of stay; median waiting time; left without being seen, 72-h revisit and
      mortality rates, and daily number of visits. There was no additional staff or bed
      after lean implementation. Results: Despite an increment in the daily number of
      visits (+8.3%, P < 0.001), significant reductions in process time of discharged
      (182 vs 160 min, P < 0.001) and transferred to observation (186 vs 176 min, P <
      0.001) patients, in length of stay (389 vs 329 min, P < 0.001), and in waiting
      time (71 vs 48 min, P < 0.001) were achieved after lean implementation. No
      significant differences were registered in left without being seen rate (5.23% vs
      4.95%), 72-h revisit rate (3.41% vs 3.93%), and mortality rate (0.23% vs 0.15%).
      Conclusion: Lean thinking is a methodology that can improve triage acuity level-3
      patient flow in the ED, resulting in better throughput along with reduced waiting
      time.

PMID- 29447353
TI  - Association of strategic management with vaccination in the terms of
      globalization.
AB  - Globalization is having an ever growing impact on the field of vaccine production
      and distribution in the world and domestically. In this article we examine the
      impact of taking a strategic approach to vaccination programmes by all the
      relevant actors: WHO, UNICEF, national immunization programmes, and vaccine
      manufacturers and distributors. The review of the relevant literature indicates
      that there are commonalities to the worldwide vaccination programmes. A
      comparative analysis of various vaccination strategies recommended by WHO and the
      immunization calendars of certain European countriesis made as well as an
      analysis of the Serbian vaccination programme. New and more expensive vaccines
      will continue to appear on the market in increasingly short periods of time.

PMID- 29447354
TI  - CREB3 regulatory factor -mTOR-autophagy regulates goat endometrial function
      during early pregnancy.
AB  - In domestic ruminants, a receptive endometrium is crucial for successful
      pregnancy. Although many essential molecular modulators and pathways have been
      identified during early pregnancy, the precise mechanisms regulating goat
      endometrial function remains largely unknown. Here, we describe a novel regulator
      during early pregnancy, whereby hormones increased CREB3 regulatory factor
      (CREBRF) expression and act as a potential activator of autophagy in endometrial
      epithelial cells (EECs) via the mTOR pathway. Our results showed that knockdown
      of CREBRF via shCREBRF hampered EECs proliferation by S-phase cell cycle arrest
      and significantly inhibited endometrial function. We also reported that CREBRF
      mTOR-autophagy pathway plays a vital role in regulating endometrial function,
      with a blockade of the mTOR by rapamycin demonstrating the regulatory function on
      prostaglandin (PGs) secretion and cell attachment in EECs. Moreover, chloroquine
      pretreatment also proved the above conclusion. Collectively, our findings provide
      new insight into the molecular mechanisms of goat endometrial function and
      indicate that the CREBRF-mTOR-autophagy pathway plays a central role in PGs
      secretion and cell attachment.

PMID- 29447355
TI  - A recurrent de novo missense mutation in UBTF causes developmental
      neuroregression.

PMID- 29447356
TI  - Barriers to the availability and accessibility of controlled medicines for
      chronic pain in Africa.
AB  - Africans endure a high burden of pain and suffering from HIV/AIDS and cancer, yet
      receive a meager amount of the world's pain medication. This tragedy occurs
      needlessly, given that inexpensive, effective and easily administered
      interventions are available. WHO has a 'three-step analgesic ladder' framework
      for managing cancer pain. This widely adopted clinical practice guideline is an
      integral part of palliative care programs and has also been applied to non-cancer
      pain. However, untreated pain is a major public health problem due to the
      discordance between scientific evidence and public policy. Historically, the
      International Narcotics Board has taken an unbalanced prohibitionist approach to
      international drug control that has emphasized suppressing controlled substances
      over making them available for medical and scientific purposes. The procurement
      process for controlled pain medications in most African countries is a morass of
      restrictions that make it exceedingly difficult for patients to obtain these
      drugs. Often, these restrictions arise in part from a misunderstanding of
      addiction and dependence on opiates. The result has been widespread 'opiophobia'
      among African policy makers and physicians. A host of factors have misaligned the
      analgesic pharmaceutical supply chain. Taken together, access to medically
      necessary controlled substance in sub-Saharan Africa is suboptimal.

PMID- 29447357
TI  - Analysis of cluster-randomized test-negative designs: cluster-level methods.
AB  - Intervention trials of vector control methods often require community level
      randomization with appropriate inferential methods. For many interventions, the
      possibility of confounding due to the effects of health-care seeking behavior on
      disease ascertainment remains a concern. The test-negative design, a variant of
      the case-control method, was introduced to mitigate this issue in the assessment
      of the efficacy of influenza vaccination (measured at an individual level) on
      influenza infection. Here, we introduce a cluster-randomized test-negative design
      that includes randomization of the intervention at a group level. We propose
      several methods for estimation and inference regarding the relative risk (RR).
      The inferential methods considered are based on the randomization distribution
      induced by permuting intervention assignment across two sets of randomly selected
      clusters. The motivating example is a current study of the efficacy of randomized
      releases of Wolbachia-infected Aedes aegypti mosquitoes to reduce the incidence
      of dengue in Yogyakarta City, Indonesia. Estimation and inference techniques are
      assessed through a simulation study.

PMID- 29447358
TI  - Factors associated with maternal utilization of health facilities for delivery in
      Ethiopia.
AB  - Background: As a signatory of the Millennium Development Goals, Ethiopia has made
      significant achievements towards meeting the maternal mortality related goals
      since 1990. Despite that, the country is still experiencing unacceptably high
      maternal mortality rates, and challenges to improving the coverage and
      utilisation of health facility delivery services which represent a key strategy
      to combat maternal mortality. Currently, there is limited evidence on the factors
      associated with health facility delivery in Ethiopia. Therefore, the objective of
      this study was to identify the correlates of facility delivery among urban and
      rural women in Ethiopia. Methods: This was a cross-sectional study based on data
      from the 2011 Ethiopian Demographic and Health Survey. Participants were 7540
      women aged between 15 and 49 years with a history of at least one birth. The
      outcome variable was place of delivery. Data were analyzed using bivariate and
      multivariable regression techniques. Results: The overall prevalence of health
      facility delivery was 17.1% (1447/7540). In the multivariable regression
      analysis, education, wealth status, frequency of antenatal care visits and
      mother's age at first birth were found to be significantly associated with
      women's choice of place of delivery. Among urban women, those who had primary and
      secondary/higher level education had increased odds of delivering at a health
      facility compared with those without formal education. Those who were from the
      richest households had higher odds of delivering at a health facility compared
      with those in the lowest class. In urban and rural areas, compared with those who
      had no ANC visits, those who had at least four visits also had increased odds of
      delivering at a health facility. In the urban areas, those who were over 18 years
      old at their first childbirth had significantly higher odds of choosing to
      deliver at a health facility. Conclusion: Findings show that the prevalence of
      healthy facility delivery in Ethiopia is remarkably low. Addressing the
      sociodemographic and wealth inequities can help promote the utilisation of
      facility delivery in both urban and rural areas. Policy-makers should consider
      improving access to education as a strategy to meet maternal health related goals
      and treat education as a multipronged strategy. Providing free healthcare access
      could be one strategy to achieve the universal coverage of essential maternal
      healthcare services.

PMID- 29447359
TI  - ACTN3 genotype and physical function and frailty in an elderly Chinese
      population: the Rugao Longevity and Ageing Study.
AB  - Objective: To examine the associations of the actinin alpha 3 gene (ACTN3) R577X
      polymorphism with physical performance and frailty in an older Chinese
      population. Methods: Data from 1,463 individuals (57.8% female) aged 70-87 years
      from the Rugao Longevity and Ageing Study were used. The associations between
      R577X and timed 5-m walk, grip strength, timed Up and Go test, and frailty index
      (FI) based on deficits of 23 laboratory tests (FI-Lab) were examined. Analysis of
      variance and linear regression models were used to evaluate the genetic effects
      of ACTN3 R577X on physical performance and FI-Lab. Results: The XX and RX
      genotypes of the ACTN3 R557X polymorphism accounted for 17.1 and 46.9%,
      respectively. Multivariate regression analysis revealed that in men aged 70-79
      years, the ACTN3 577X allele was significantly associated with physical
      performance (5-m walk time, regression coefficient (beta) = 0.258, P = 0.006;
      grip strength, beta = -1.062, P = 0.012; Up and Go test time beta = 0.368, P =
      0.019). In women aged 70-79 years, a significant association between the ACTN3
      577X allele and the FI-Lab score was observed, with a regression coefficient of
      beta = 0.019 (P = 0.003). These findings suggest an age- and gender-specific X
      additive model of R577X for 5-m walk time, grip strength, Up and Go Test time,
      and FI-Lab score. Conclusion: The ACTN3 577X allele is associated with an age-
      and sex-specific decrease in physical performance and an increase in frailty in
      an older population.

PMID- 29447360
TI  - Allocation of Treatment Responsibility in Adolescents With Epilepsy: Associations
      With Cognitive Skills and Medication Adherence.
AB  - Objectives: To describe allocation of treatment responsibility (ATR) in
      adolescents with epilepsy, investigate associations between cognitive skills and
      ATR, and examine whether ATR for antiepileptic drugs (AEDs) predicted
      electronically monitored adherence. Method: Sixty adolescents with epilepsy and
      their caregivers completed the Allocation of Treatment Responsibility Scale and a
      battery of self-report measures. Medical chart review data and electronically
      monitored AED adherence were collected for 1 year. Descriptive data assessed ATR
      for caregivers and adolescents; multivariate hierarchical regressions tested
      associations between variables. Results: ATR for labs and clinic appointments was
      greatest for caregivers, while ATR for AEDs was more likely to be shared between
      caregiver and adolescent. Poorer attention was associated with greater caregiver
      responsibility for AEDs. Greater caregiver responsibility for AEDs was associated
      with higher electronically monitored adherence over 12 months. Conclusions: In
      adolescents with epilepsy, caregivers are responsible for most treatment tasks,
      although responsibility for taking medication was shared with the adolescent.
      Greater caregiver responsibility for medication results in better long-term AED
      adherence. ATR is an important construct that warrants further attention in
      research and clinical practice, especially in the context of transition and
      health outcomes in pediatric epilepsy.

PMID- 29447361
TI  - Laryngeal squamous cell papilloma is highly associated with human papillomavirus.
AB  - Objective: To delineate the association between characteristics of adult-onset
      laryngeal squamous cell papilloma and human papillomavirus (HPV) infection.
      Methods: Clinical records and paraffin-embedded specimens of 77 papilloma
      patients who had been treated between 1998 and 2014 were collected. Of the 77
      cases, 34 were identified in the larynx, 28 in the oral cavity and 15 in the
      oropharynx. Specimens were investigated by polymerase chain reaction (PCR) to
      detect HPV 6, 11, 16, 18, 31, 33, 35, 52b and 58, and immunohistochemical (IHC)
      staining for anti-p16INK4a antibody. Results: In 21 cases (61.8%) with laryngeal
      squamous cell papilloma, various types of HPV were detected: 14 cases (41.2%)
      were positive of high-risk HPV, 18 (52.9%) were positive of low-risk HPV and 11
      (32.4%) were positive of both high-risk HPV and low-risk HPV. Younger patients
      (<60 years) showed a higher rate of HPV infection than older patients. Among the
      34 cases with laryngeal papilloma, no malignant transformation was observed
      during the study period. With IHC staining, positive expression of p16 was
      observed in 20 cases (58.8%). HPV infection and p16-expression were associated
      with the pathological finding of koilocytosis. Only four cases (14.3%) showed HPV
      positivity in the oral cavity, and none of the 15 oropharyngeal cases were
      positive for HPV, and none of the oral cavity and oropharyngeal cases showed
      koilocytosis. Results of HPV-PCR and p16-IHC staining were significantly
      correlated each other. Conclusions: HPV infection is frequently associated with
      laryngeal squamous cell papilloma, and koilocytosis is a characteristic
      pathological finding. To the best of our knowledge, this is the first report
      which have described infections with multiple HPV types in laryngeal papilloma.

PMID- 29447362
TI  - EQ-5D-Y for the assessment of health-related quality of life among Taiwanese
      youth with mild-to-moderate chronic kidney disease.
AB  - Objective: To assess if health-related quality of life (HRQOL) of children with
      chronic kidney disease (CKD) and different comorbid conditions can be identified
      based on the EQ-5D child-friendly version (EQ-5D-Y). Design: Prospective cross
      sectional study. Setting: A tertiary care medical center in Taiwan. Study
      participants: All CKD patients aged 7-18 years treated at the center between May
      2014 and December 2016. Main Outcome Measures: HRQOL assessment was done using EQ
      5D-Y. Spearman correlation tests were used for construct validity of the
      traditional Chinese version of EQ-5D-Y. Test-retest reliability was determined
      through Cohen's kappa values and intraclass correlation coefficients (ICC).
      Laboratory results and CKD-related morbid conditions were ascertained and
      assessed their associations with HRQOL score using multivariate linear
      regression. Results: Of 68 participants, 53 of them completed two HRQOL
      assessments of HRQOL at least 6-month. Cross-sectional analysis revealed fair to
      moderate correlations between EQ visual analogue score and patient
      characteristics. Older children at assessment (P < 0.01), girls (P = 0.03) and
      presence of mineral bone disorders had a significantly negative impact on HRQOL.
      Children self-reported EQ-5D-Y dimensions were found to be fairly to highly
      reliable (kappa = 0.2 to 0.8), except for 'pain/discomfort' and
      'anxiety/depression'. Conclusions: The EQ-5D-Y discriminated among children with
      different level of CKD-related clinical burden, but the psychometric properties
      may be limited in some HRQOL dimensions. Further research will need to address
      factors that may threaten validity and reliability data provided by children and
      adolescents.

PMID- 29447363
TI  - Noise reduction in CCD measurements by improving the quality of dark-reference
      images.
AB  - This publication is a systematic investigation of the effect the improvement of
      dark-reference images has on the resulting bright-field images. For this, data
      were acquired with three different charge-coupled device cameras attached to two
      different transmission electron microscopes. Multi-frame acquisitions and methods
      to correct x-ray noise are introduced and quantified as options to improve the
      dark-reference images. Furthermore, the influence of x-ray noise on transmission
      electron microscopy measurements is discussed and observations on its composition
      are shared.

PMID- 29447364
TI  - Salzburg Global Seminar Session 565-'Better Health Care: how do we learn about
      improvement?'
AB  - A fundamental question for the field of healthcare improvement is the extent to
      which the results achieved can be attributed to the changes that were implemented
      and whether or not these changes are generalizable. Answering these questions is
      particularly challenging because the healthcare context is complex, and the
      interventions themselves tend to be complex and multi-dimensional. The Salzburg
      Global Seminar Session 565-'Better Health Care: How do we learn about
      improvement?' was convened to address questions of attribution, generalizability
      and rigor, and to think through how to approach these concerns in the field of
      quality improvement. The Salzburg Global Seminar Session 565 brought together 61
      leaders in improvement from 22 countries, including researchers, evaluators and
      improvers. The primary conclusion that resulted from the session was the need for
      evaluation to be embedded as an integral part of the improvement. We have invited
      participants of the seminar to contribute to writing this supplement, which
      consists of eight articles reflecting insights and learning from the Salzburg
      Global Seminar. This editorial serves as an introduction to the supplement. The
      supplement explains results and insights from Salzburg Global Seminar Session
      565.

PMID- 29447365
TI  - Cohort Profile: The Quebec Birth Cohort on Immunity and Health (QBCIH).

PMID- 29447367
TI  - Endometrial natural killer (NK) cells reveal a tissue-specific receptor
      repertoire.
AB  - STUDY QUESTION: Is the natural killer (NK) cell receptor repertoire of
      endometrial NK (eNK) cells tissue-specific? SUMMARY ANSWER: The NK cell receptor
      (NKR) expression profile in pre-pregnancy endometrium appears to have a unique
      tissue-specific phenotype, different from that found in NK cells in peripheral
      blood, suggesting that these cells are finely tuned towards the reception of an
      allogeneic fetus. WHAT IS KNOWN ALREADY: NK cells are important for successful
      pregnancy. After implantation, NK cells encounter extravillous trophoblast cells
      and regulate trophoblast invasion. NK cell activity is amongst others regulated
      by C-type lectin heterodimer (CD94/NKG2) and killer cell immunoglobulin-like
      (KIR) receptors. KIR expression on decidual NK cells is affected by the presence
      of maternal HLA-C and biased towards KIR2D expression. However, little is known
      about NKR expression on eNK cells prior to pregnancy. STUDY DESIGN SIZE,
      DURATION: In this study, matched peripheral and menstrual blood (a source of
      endometrial cells) was obtained from 25 healthy females with regular menstrual
      cycles. Menstrual blood was collected during the first 36 h of menstruation using
      a menstrual cup, a non-invasive technique to obtain endometrial cells.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: KIR and NKG2 receptor expression on eNK
      cells was characterized by 10-color flow cytometry, and compared to matched pbNK
      cells of the same female. KIR and HLA-C genotypes were determined by PCR-SSOP
      techniques. Anti-CMV IgG antibodies in plasma were measured by chemiluminescence
      immunoassay. MAIN RESULTS AND THE ROLE OF CHANCE: KIR expression patterns of eNK
      cells collected from the same female do not differ over consecutive menstrual
      cycles. The percentage of NK cells expressing KIR2DL2/L3/S2, KIR2DL3, KIR2DL1,
      LILRB1 and/or NKG2A was significantly higher in eNK cells compared to pbNK cells,
      while no significant difference was observed for NKG2C, KIR2DL1/S1, and KIR3DL1.
      The NKR repertoire of eNK cells was clearly different from pbNK cells, with eNK
      cells co-expressing more than three NKR simultaneously. In addition, outlier
      analysis revealed 8 and 15 NKR subpopulation expansions in eNK and pbNK cells,
      respectively. In contrast to the pbNK cell population, the expansions present in
      the eNK cell population were independent of CMV status and HLA-C genotype.
      Moreover, the typical NKG2C imprint induced by CMV infection on pbNK cells was
      not observed on eNK cells from the same female, suggesting a rapid local turnover
      of eNK cells and/or a distinct licensing process. LIMITATIONS REASONS FOR
      CAUTION: Based on our previous work and the parameters studied here, menstrual
      blood-derived eNK cells closely resemble biopsy-derived eNK cells. However,
      sampling is not done at the exact same time during the menstrual cycle, and
      therefore we cannot exclude some, as yet undetected, differences. WIDER
      IMPLICATIONS OF THE FINDINGS: Our data reveals that NK cells in the pre
      implantation endometrium appear to have a dedicated tissue-specific phenotype,
      different from NK cells in peripheral blood. This may indicate that eNK cells are
      finely tuned to receive an allogeneic fetus. Studying the endometrial NKR
      repertoire of women with pregnancy related problems could provide clues to
      understand the pathogenesis of pregnancy complications. STUDY FUNDING/COMPETING
      INTEREST(S): No external funding was obtained for the present study. None of the
      authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: NA.

PMID- 29447368
TI  - Venovenous malformation developed prior to a Kawashima operation in a patient
      with an interrupted inferior vena cava.
AB  - An 11-month-old girl with an unbalanced atrioventricular septal defect,
      coarctation of the aorta and an interrupted inferior vena cava with hemiazygos
      continuation post-surgical status of coarctation repair and pulmonary artery
      banding underwent a Kawashima operation. Severe hypoxia occurred immediately
      after she was weaned from cardiopulmonary bypass, which was successfully resolved
      by the ligation of the hemiazygos vein. Postoperative enhanced computed
      tomography detected significant venovenous malformation from the hemiazygos vein
      to the left renal vein.

PMID- 29447366
TI  - Parent-of-Origin-Dependent Gene Expression in Male and Female Schistosome
      Parasites.
AB  - Schistosomes are the causative agents of schistosomiasis, a neglected tropical
      disease affecting over 230 million people worldwide. Additionally to their major
      impact on human health, they are also models of choice in evolutionary biology.
      These parasitic flatworms are unique among the common hermaphroditic trematodes
      as they have separate sexes. This so-called "evolutionary scandal" displays a
      female heterogametic genetic sex-determination system (ZZ males and ZW females),
      as well as a pronounced adult sexual dimorphism. These phenotypic differences are
      determined by a shared set of genes in both sexes, potentially leading to
      intralocus sexual conflicts. To resolve these conflicts in sexually selected
      traits, molecular mechanisms such as sex-biased gene expression could occur, but
      parent-of-origin gene expression also provides an alternative. In this work we
      investigated the latter mechanism, that is, genes expressed preferentially from
      either the maternal or the paternal allele, in Schistosoma mansoni species. To
      this end, transcriptomes from male and female hybrid adults obtained by strain
      crosses were sequenced. Strain-specific single nucleotide polymorphism (SNP)
      markers allowed us to discriminate the parental origin, while reciprocal crosses
      helped to differentiate parental expression from strain-specific expression. We
      identified genes containing SNPs expressed in a parent-of-origin manner
      consistent with paternal and maternal imprints. Although the majority of the SNPs
      was identified in mitochondrial and Z-specific loci, the remaining SNPs found in
      male and female transcriptomes were situated in genes that have the potential to
      explain sexual differences in schistosome parasites. Furthermore, we identified
      and validated four new Z-specific scaffolds.

PMID- 29447369
TI  - Mandatory Change From Surgical Skull Caps to Bouffant Caps Among Operating Room
      Personnel Does Not Reduce Surgical Site Infections in Class I Surgical Cases: A
      Single-Center Experience With More Than 15 000 Patients.
AB  - BACKGROUND: Surgical site infections (SSIs) are noteworthy and costly
      complications. New recommendations from a national organization have urged the
      elimination of traditional surgeon's caps (surgical skull caps) and mandated the
      use of bouffant caps to prevent SSIs. OBJECTIVE: To report SSI rates for >15 000
      class I (clean) surgical procedures 13 mo before and 13 mo after surgical skull
      caps were banned at a single site with 25 operating rooms. METHODS: SSI data were
      acquired from hospital infection control monthly summary reports from January
      2014 to March 2016. Based on a change in hospital policy mandating obligatory use
      of bouffant caps since February 2015, data were categorized into nonbouffant and
      bouffant groups. Monthly and cumulative infection rates for 13 mo before (7513
      patients) and 13 mo after (8446 patients) the policy implementation were
      collected and analyzed for the groups, respectively. RESULTS: An overall increase
      of 0.07% (0.77%-0.84%) in the cumulative rate of SSI in all class I operating
      room cases and of 0.03% (0.79%-0.82%) in the cumulative rate of SSI in all spinal
      procedures was noted. However, neither increase reached statistical significance
      (P > .05). The cumulative rate of SSI in neurosurgery craniotomy/craniectomy
      cases decreased from 0.95% to 0.75%; this was also not statistically significant
      (P = 1.00). CONCLUSION: National efforts at improving healthcare performance are
      laudable but need to be evidence based. Guidelines, especially when applied in a
      mandatory fashion, should be assessed for effectiveness. In this large, single
      center series of patients undergoing class I surgical procedures, elimination of
      the traditional surgeon's cap did not reduce infection rates.

PMID- 29447370
TI  - Management of gout by UK rheumatologists: a British Society for Rheumatology
      national audit.
AB  - Objectives: To assess the concordance of gout management by UK rheumatologists
      with evidence-based best-practice recommendations. Methods: Data were collected
      on patients newly referred to UK rheumatology out-patient departments over an 8
      week period. Baseline data included demographics, method of diagnosis, clinical
      features, comorbidities, urate-lowering therapy (ULT), prophylaxis and blood
      tests. Twelve months later, the most recent serum uric acid level was collected.
      Management was compared with audit standards derived from the 2006 EULAR
      recommendations, 2007 British Society for Rheumatology/British Health
      Professionals in Rheumatology guideline and the National Institute for Health and
      Care Excellence febuxostat technology appraisal. Results: Data were collected for
      434 patients from 91 rheumatology departments (mean age 59.8 years, 82% male).
      Diagnosis was crystal-proven in 13%. Of 106 taking a diuretic, this was
      reduced/stopped in 29%. ULT was continued/initiated in 76% of those with one or
      more indication for ULT. One hundred and fifty-eight patients started
      allopurinol: the starting dose was most commonly 100 mg daily (82%); in those
      with estimated glomerular filtration rate <60 ml/min the highest starting dose
      was 100 mg daily. Of 199 who started ULT, prophylaxis was co-prescribed for 94%.
      Fifty patients started a uricosuric or febuxostat: 84% had taken allopurinol
      previously. Of 44 commenced on febuxostat, 18% had a history of heart disease. By
      12 months, serum uric acid levels ?360 and <300 MUmol/l were achieved by 45 and
      25%, respectively. Conclusion: Gout management by UK rheumatologists concords
      well with guidelines for most audit standards. However, fewer than half of
      patients achieved a target serum uric level over 12 months. Rheumatologists
      should help ensure that ULT is optimized to achieve target serum uric acid levels
      to benefit patients.

PMID- 29447371
TI  - Getting shops to voluntarily stop selling cheap, strong beers and ciders: a time
      series analysis evaluating impacts on alcohol availability and purchasing.
AB  - Background: 'Reducing the Strength' (RtS) is a public health initiative
      encouraging retailers to voluntarily stop selling cheap, strong beers/ciders
      (>=6.5% alcohol by volume). This study evaluates the impact of RtS initiatives on
      alcohol availability and purchasing in three English counties with a combined
      population of 3.62 million people. Methods: We used a multiple baseline time
      series design to examine retail data over 29 months from a supermarket chain that
      experienced a two-wave, area-based role out of RtS: initially 54 stores (W1),
      then another 77 stores (W2). We measured impacts on units of alcohol sold
      (primary outcome: beers/ciders; secondary outcome: all alcoholic products),
      economic impacts on alcohol sales and substitution effects. Results: We observed
      a non-significant W1 increase (+3.7%, 95% CI: -11.2, 21.0) and W2 decrease (
      6.8%, 95% CI: -20.5, 9.4) in the primary outcome. We observed a significant W2
      decrease in units sold across all alcohol products (-10.5%, 95% CI: -19.2, -0.9).
      The direction of effect between waves was inconsistent for all outcomes,
      including alcohol sales, with no evidence of substitution effects. Conclusions:
      In the UK, voluntary RtS initiatives appear to have little or no impact on
      reducing alcohol availability and purchase from the broader population of
      supermarket customers.

PMID- 29447372
TI  - Small Fiber Polyneuropathy Is Prevalent in Patients Experiencing Complex Chronic
      Pelvic Pain.
AB  - Objective: To demonstrate the prevalence of small fiber polyneuropathy (SFPN) in
      patients with refractory chronic pelvic pain (CPP). Design: Retrospective study
      of prospective database. Subjects: Participants were complex CPP patients
      recruited from subspecity referral clinics defined as those who were refractory
      to initial treatment and/or exhibited comorbid pain syndromes at initial
      presentation. Methods: Comprehensive treatment history for CPP was obtained, and
      participants referred as above; 3-mm punch biopsies were obtained of the lower
      extremity and sent to diagnostic reference labs to evaluate for SFPN. The
      reported lab sensitivity and specificity for SFPN are 78-92% and 65-90%,
      respectively. Results: Twenty-five of 39 patients (64%) were positive for SFPN.
      Comorbid conditions noted in our population included gastroesophageal reflux
      disease (46%), migraine (38%), irritable bowel syndrome (33%), lower back pain
      (33%), fibromyalgia (38%), endometriosis (15%), interstitial cystitis (18%),
      vulvodynia (5%), and other chronic pain syndromes (36%). Conclusions: The
      prevalence of SFPN in our specialty referral patients with complex CPP is
      remarkably high vs published general population prevalence data (53/100,000).
      Identification of SFPN in this complex population shifts the focus from undefined
      syndromes to symptom complexes with linked potentially treatable mechanisms
      (e.g., SFPN, central sensitization). Most CPP patients with SFPN are undiagnosed.
      Considering the diagnosis may expand treatment options beyond conventional or so
      called adjuvant analgesics. Treatment may expand to therapies such as IV
      lidocaine, IVIG, or other immunomodulatory options. In addition, the value to the
      patient of receiving a diagnosis for a multisystem or refractory pain syndrome,
      often attributed to negative psychologic factors, cannot be underestimated.
      Identifying SFPN should be contemplated in CPP patients who present with
      multisystem pain or who have not responded to initial evaluation and management.

PMID- 29447374
TI  - Spectrum of Pediatric Tuberculosis in a Tertiary Care Setting in South India.
AB  - Background: Pediatric tuberculosis (TB) is often underdiagnosed with poor
      estimate of its true burden. Availability of Xpert MTB/RIF assay enhances
      diagnostic capacity of pediatric TB. Methods: A 3-year retrospective review of
      hospital records was done for all children diagnosed with confirmed and
      unconfirmed TB. Comparison was made between intrathoracic, single-site
      extrathoracic and disseminated TB. Results: In total, 274 children had TB with
      130 (47.4%) having confirmed TB. Pulmonary (23.4%), lymph node (23%) and central
      nervous system (12.8%) TB were the three commonest forms. HIV TB coinfection was
      2.9%. Mycobacterial culture was positive in 90 (32.8%) and XPert MTB/RIF in 85
      patients (31%). Mycobacterial confirmation was obtained in 45 (56.3%)
      intrathoracic TB, 69 (45.4%) extrathoracic TB and 16 (38.1%) disseminated TB.
      Correlation between positive Xpert and mycobacterial culture was poor (kappa
      0.38). Rifampicin resistance was present in 25 (19.2%) of the 130
      microbiologically confirmed TB. Conclusion: Extrathoracic TB is common in
      children. Mycobacterial confirmation in pediatric TB is improved with use of
      Xpert.

PMID- 29447373
TI  - Coupling the core of the anticancer drug etoposide to an oligonucleotide induces
      topoisomerase II-mediated cleavage at specific DNA sequences.
AB  - Etoposide and other topoisomerase II-targeted drugs are important anticancer
      therapeutics. Unfortunately, the safe usage of these agents is limited by their
      indiscriminate induction of topoisomerase II-mediated DNA cleavage throughout the
      genome and by a lack of specificity toward cancer cells. Therefore, as a first
      step toward constraining the distribution of etoposide-induced DNA cleavage sites
      and developing sequence-specific topoisomerase II-targeted anticancer agents, we
      covalently coupled the core of etoposide to oligonucleotides centered on a
      topoisomerase II cleavage site in the PML gene. The initial sequence used for
      this 'oligonucleotide-linked topoisomerase inhibitor' (OTI) was identified as
      part of the translocation breakpoint of a patient with acute promyelocytic
      leukemia (APL). Subsequent OTI sequences were derived from the observed APL
      breakpoint between PML and RARA. Results indicate that OTIs can be used to direct
      the sites of etoposide-induced DNA cleavage mediated by topoisomerase IIalpha and
      topoisomerase IIbeta. OTIs increased levels of enzyme-mediated cleavage by
      inhibiting DNA ligation, and cleavage complexes induced by OTIs were as stable as
      those induced by free etoposide. Finally, OTIs directed against the PML-RARA
      breakpoint displayed cleavage specificity for oligonucleotides with the
      translocation sequence over those with sequences matching either parental gene.
      These studies demonstrate the feasibility of using oligonucleotides to direct
      topoisomerase II-mediated DNA cleavage to specific sites in the genome.

PMID- 29447375
TI  - Coupling individual kernel-filling processes with source-sink interactions into
      GREENLAB-Maize.
AB  - Background and Aims: Failure to account for the variation of kernel growth in a
      cereal crop simulation model may cause serious deviations in the estimates of
      crop yield. The goal of this research was to revise the GREENLAB-Maize model to
      incorporate source- and sink-limited allocation approaches to simulate the dry
      matter accumulation of individual kernels of an ear (GREENLAB-Maize-Kernel).
      Methods: The model used potential individual kernel growth rates to characterize
      the individual potential sink demand. The remobilization of non-structural
      carbohydrates from reserve organs to kernels was also incorporated. Two years of
      field experiments were conducted to determine the model parameter values and to
      evaluate the model using two maize hybrids with different plant densities and
      pollination treatments. Detailed observations were made on the dimensions and dry
      weights of individual kernels and other above-ground plant organs throughout the
      seasons. Key Results: Three basic traits characterizing an individual kernel were
      compared on simulated and measured individual kernels: (1) final kernel size; (2)
      kernel growth rate; and (3) duration of kernel filling. Simulations of individual
      kernel growth closely corresponded to experimental data. The model was able to
      reproduce the observed dry weight of plant organs well. Then, the source-sink
      dynamics and the remobilization of carbohydrates for kernel growth were
      quantified to show that remobilization processes accompanied source-sink dynamics
      during the kernel-filling process. Conclusions: We conclude that the model may be
      used to explore options for optimizing plant kernel yield by matching maize
      management to the environment, taking into account responses at the level of
      individual kernels.

PMID- 29447376
TI  - The relationship between depression and biologic treatment response in rheumatoid
      arthritis: An analysis of the British Society for Rheumatology Biologics
      Register.
AB  - Objective: To investigate the relationship between depressive symptoms and
      treatment response and disease activity in RA over a 1-year follow-up. Methods:
      Data from the British Society for Rheumatology Biologics Register were used,
      representing 18 421 RA patients receiving biologic treatment. Depressive symptoms
      were identified through one of three assessments: reporting a history of
      depression, the Medical Outcomes Survey 36-item Short Form or the EuroQol five
      dimension scale. Logistic regression analyses examined the relationship between
      baseline depressive symptoms and odds of good treatment response by 1 year.
      Multilevel models addressed the association between baseline depressive symptoms
      and disease activity outcomes over 1-year follow-up, adjusting for age, gender,
      disease duration, comorbidities and baseline disease activity and physical
      disability. Results: Depression symptoms at biologic treatment initiation were
      associated with 20-40% reduced odds of achieving a good treatment response at 1
      year. Depressive symptoms at baseline also associated with reduced improvement in
      disease activity over the course of follow-up. Patients with a history of
      depression or reporting symptoms of depression according to the EuroQol five
      dimension scale showed reduced improvement in tender and swollen joints, patient
      global assessment and ESR over 1-year follow-up. Patients with depression
      symptoms according to the 36-item Short Form showed reduced improvement in tender
      and swollen joints, but not ESR or patient global assessment. Conclusion:
      Experiencing symptoms of depression at the start of biologics treatment may
      reduce the odds of achieving a good treatment response, and reduce improvement in
      disease activity over time. Depression should be managed as part of routine
      clinical care to optimize treatment outcomes.

PMID- 29447378
TI  - Trace metal metabolism in plants.
AB  - Many trace metals are essential micronutrients, but also potent toxins. Due to
      natural and anthropogenic causes, vastly different trace metal concentrations
      occur in various habitats, ranging from deficient to toxic levels. Therefore, one
      focus of plant research is on the response to trace metals in terms of uptake,
      transport, sequestration, speciation, physiological use, deficiency, toxicity,
      and detoxification. In this review, we cover most of these aspects for the
      essential micronutrients copper, iron, manganese, molybdenum, nickel, and zinc to
      provide a broader overview than found in other recent reviews, to cross-link
      aspects of knowledge in this very active research field that are often seen in a
      separated way. For example, individual processes of metal usage, deficiency, or
      toxicity often were not mechanistically interconnected. Therefore, this review
      also aims to stimulate the communication of researchers following different
      approaches, such as gene expression analysis, biochemistry, or biophysics of
      metalloproteins. Furthermore, we highlight recent insights, emphasizing data
      obtained under physiologically and environmentally relevant conditions.

PMID- 29447377
TI  - Behavioral and neural indices of affective coloring for neutral social stimuli.
AB  - Emotional processing often continues beyond the presentation of emotionally
      evocative stimuli, which can result in affective biasing or coloring of
      subsequently encountered events. Here, we describe neural correlates of affective
      coloring and examine how individual differences in affective style impact the
      magnitude of affective coloring. We conducted functional magnetic resonance
      imaging in 117 adults who passively viewed negative, neutral and positive
      pictures presented 2 s prior to neutral faces. Brain responses to neutral faces
      were modulated by the valence of preceding pictures, with greater activation for
      faces following negative (vs positive) pictures in the amygdala, dorsomedial and
      lateral prefrontal cortex, ventral visual cortices, posterior superior temporal
      sulcus, and angular gyrus. Three days after the magnetic resonance imaging scan,
      participants rated their memory and liking of previously encountered neutral
      faces. Individuals higher in trait positive affect and emotional reappraisal
      rated faces as more likable when preceded by emotionally arousing (negative or
      positive) pictures. In addition, greater amygdala responses to neutral faces
      preceded by positively valenced pictures were associated with greater memory for
      these faces 3 days later. Collectively, these results reveal individual
      differences in how emotions spill over onto the processing of unrelated social
      stimuli, resulting in persistent and affectively biased evaluations of such
      stimuli.

PMID- 29447379
TI  - Acute exercise is not cardioprotective and may induce apoptotic signalling in
      heart surgery: a randomized controlled trial.
AB  - OBJECTIVES: During open-heart surgery, the myocardium experiences ischaemia
      reperfusion injury. A single bout of moderate, 30-min exercise induces
      preconditioning and protects the heart from ischaemia-reperfusion injury in rats,
      but this has never been investigated in humans. We aimed to investigate whether 1
      bout of moderate exercise 24 h prior to surgery protects against mitochondrial
      and cardiac damage. METHODS: Patients scheduled for elective coronary artery
      bypass were eligible for this pilot study. Twenty were included and randomized to
      the treadmill exercise group (the EX group, n = 10) 24 h preoperatively or to
      standard presurgical procedures (control n = 10). Right atrial (RA) and left
      ventricular (LV) biopsies were collected immediately before and as long as
      possible after aortic cross-clamping to assess the primary outcome of
      mitochondrial respiration by respirometry, in addition to reactive oxygen species
      production by fluorometry and apoptotic transcripts. Cardiac troponin T and
      creatine kinase myocardial brain were measured in plasma at arrival, before
      surgery and 6 and 24 h postoperatively. RESULTS: Mitochondrial respiration was
      lower in the EX group after surgery in the LV (Complex I -22%, P < 0.05 and
      maximal -23%, P < 0.05) and the right atrium (Complex I -25%, P < 0.05).
      Transcript level of the apoptosis-related marker caspase 3 was increased 1.5-fold
      in the LV prior to surgery in the EX group when compared with the control group,
      P < 0.05. Cardiac troponin T was 45% higher in the EX group than in the control
      group 6 h postoperatively (P = 0.03), although not significant when corrected for
      aortic cross-clamping time. CONCLUSIONS: Results indicate that exercise did not
      precondition the heart against surgery-related damage. Exercise may render the
      myocardium and mitochondria more vulnerable to perioperative damage. Clinical
      trials registration number: NCT00218985
      (https://clinicaltrials.gov/ct2/show/NCT00218985).

PMID- 29447380
TI  - Sirtuins in gamete biology and reproductive physiology: emerging roles and
      therapeutic potential in female and male infertility.
AB  - BACKGROUND: Sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases that
      catalyze post-translational modifications of proteins. Together, they respond to
      metabolic challenges, inflammatory signals or hypoxic/oxidative stress, and are
      associated with aging and longevity. The role of Sirtuins in the regulation of
      fertility emerged in 2003 when a defective reproductive phenotype was observed in
      SIRT1-null mice. Although studies on Sirtuins in reproductive biology have been
      increasing in the last years, a recent comprehensive update on this issue is
      still lacking. OBJECTIVE AND RATIONALE: This review is aimed to provide knowledge
      on the activation mechanism and cellular role of Sirtuins and to give an update
      of the rapid development of Sirtuin research in female and male reproduction
      under physiological and pathological conditions. The final goal is to assess
      whether strategies aimed to improve Sirtuin expression or activity could have
      therapeutic potential for infertility associated with polycystic ovarian syndrome
      (PCOS), endometriosis, diabetes, xenobiotic stress and aging. SEARCH METHODS: The
      MEDLINE database was examined for peer-reviewed original articles. The following
      keywords were searched: 'Sirtuin', 'ovary', 'oocyte', 'ovarian follicle',
      'embryo', 'endometrium', 'sperm' and 'testis'. These keywords were combined with
      other search phrases relevant to the topic. OUTCOMES: Our knowledge of Sirtuins
      in reproductive functions has grown exponentially over the last few years. The
      majority of the work carried out so far has focused on SIRT1 with a prevalence of
      studies on female reproduction. Numerous studies have provided evidence that down
      regulation of SIRT1 is associated with physiological or pathological reduction of
      ovarian reserve. SIRT1 has also been shown to regulate proliferation and
      apoptosis in granulosa cells whereas SIRT3 was found to promote luteinisation.
      Biochemical modulation of Sirtuin activity has led to discoveries of the roles of
      SIRT1, SIRT2, SIRT3 and SIRT6 in improving the competence of oocytes grown or
      matured in vitro in humans and animal models. Recently, SIRT1, SIRT2 and SIRT3
      have emerged as protectors of oocyte against postovulatory aging. Transgenic
      models provide strong evidence that SIRT1 is involved in spermatogenesis by
      influencing specific functions of male germ cell, Sertoli cells and Leydig cells.
      When our attention moves to post-fertilization events, maternally derived SIRT3
      appears crucial in the protecting early embryos against stress conditions.
      Finally, increasing SIRT1 activity may have the potential to ameliorate fertility
      in PCOS, diabetes, endometriosis, xenobiotic stress and aging. Overall, these
      effects have been ascribed to Sirtuin-mediated regulation of energy homoeostasis,
      mitochondrial biogenesis, chromatin remodelling and protection against oxidative
      stress. WIDER IMPLICATIONS: The present review provides challenges and
      opportunities to stimulate research and exploit Sirtuin-based signalling as
      diagnostic tools and potential targets for therapeutic applications in
      reproductive medicine.

PMID- 29447381
TI  - DNA mismatch repair and oligonucleotide end-protection promote base-pair
      substitution distal from a CRISPR/Cas9-induced DNA break.
AB  - Single-stranded oligodeoxyribonucleotide (ssODN)-mediated repair of CRISPR/Cas9
      induced DNA double-strand breaks (DSB) can effectively be used to introduce small
      genomic alterations in a defined locus. Here, we reveal DNA mismatch repair (MMR)
      activity is crucial for efficient nucleotide substitution distal from the Cas9
      induced DNA break when the substitution is instructed by the 3' half of the
      ssODN. Furthermore, protecting the ssODN 3' end with phosphorothioate linkages
      enhances MMR-dependent gene editing events. Our findings can be exploited to
      optimize efficiencies of nucleotide substitutions distal from the DSB and imply
      that oligonucleotide-mediated gene editing is effectuated by templated break
      repair.

PMID- 29447382
TI  - Randomized Controlled Trial of Acupuncture for Women with Fibromyalgia: Group
      Acupuncture with Traditional Chinese Medicine Diagnosis-Based Point Selection.
AB  - Background: Group acupuncture is a growing and cost-effective method for
      delivering acupuncture in the United States and is the practice model in China.
      However, group acupuncture has not been tested in a research setting. Objective:
      To test the treatment effect of group acupuncture vs group education in persons
      with fibromyalgia. Design: Random allocation two-group study with repeated
      measures. Setting: Group clinic in an academic health center in Portland, Oregon.
      Subjects: Women with confirmed diagnosis of fibromyalgia (American College of
      Radiology 1990 criteria) and moderate to severe pain levels. Methods: Twenty
      treatments of a manualized acupuncture treatment based on Traditional Chinese
      Medicine diagnosis or group education over 10 weeks (both 900 minutes total).
      Weekly Revised Fibromyalgia Impact Questionnaire (FIQR) and Global Fatigue Index
      at baseline, five weeks, and 10 weeks and a four-week follow-up were assessed.
      Results: Thirty women were recruited, with 78% reporting symptoms for longer than
      10 years. The mean attendance was 810 minutes for acupuncture and 861 minutes for
      education. FIQR total, FIQR pain, and Global Fatigue Index all had clinically and
      statistically significant improvement in the group receiving acupuncture at end
      of treatment and four weeks post-treatment but not in participants receiving
      group education between groups. Conclusions: Compared with education, group
      acupuncture improved global symptom impact, pain, and fatigue. Furthermore, it
      was a safe and well-tolerated treatment option, improving a broader proportion of
      patients than current pharmaceutical options.

PMID- 29447385
TI  - Response to Mikel.

PMID- 29447384
TI  - Antimicrobial Prophylaxis with Combat-Related Open Soft-Tissue Injuries.
AB  - Introduction: All Department of Defense (DoD) guidance documents recommend
      cefazolin or clindamycin as post-trauma antibiotic prophylaxis for open soft
      tissue injuries. Although not advocated, some patients with open soft-tissue
      injuries also received expanded Gram-negative coverage (EGN) prophylaxis based on
      the judgment of front-line trauma providers. During the study period, revised
      guidelines in 2011/2012 re-emphasized recommendations for using cefazolin or
      clindamycin, and stewardship efforts in the DoD trauma community aimed to reduce
      the practice of adding EGN to guideline-recommended antibiotic prophylaxis. Our
      objective was to examine antibiotic utilization among wounded military personnel
      with open extremity soft-tissue injuries over a 5-yr period and assess the impact
      on infectious outcomes in patients who received EGN prophylaxis versus guideline
      directed prophylaxis. Methods: The study population included military personnel
      with open extremity soft-tissue injuries sustained in Iraq and Afghanistan (2009
      2014) who transferred to participating hospitals in the USA following medical
      evacuation. The analysis was restricted to patients who were hospitalized for at
      least seven days at a U.S. facility and excluded those who sustained open
      fractures. Post-trauma antibiotic prophylactic regimens were defined as narrow if
      they followed recommended guidance (e.g., IV cefazolin or clindamycin) or EGN
      coverage when the narrow regimen also included fluoroquinolones and/or
      aminoglycosides. Intravenous amoxicillin-clavulanate, which is commonly used at
      non-U.S. coalition theater hospitals, was also classified as narrow because it
      conformed to coalition antibiotic prophylaxis guidelines. This study was approved
      by the Infectious Disease Institutional Review Board of the Uniformed Services
      University of the Health Sciences. Results: A total of 287 wounded personnel with
      open soft-tissue injuries were assessed, of which 212 (74%) received narrow
      prophylaxis and 75 (26%) received EGN coverage (p < 0.001). Among patients in the
      narrow prophylaxis group, 81% were given cefazolin and/or clindamycin, while 19%
      received amoxicillin-clavulanate. In the EGN group, 88% and 12% received a
      fluoroquinolone and aminoglycoside, respectively. Use of EGN coverage
      significantly declined during the study period from 39% in 2009-2010 to 11% in
      2013-2014 (p < 0.001). Approximately 3% of patients who received a narrow regimen
      developed an extremity skin and soft-tissue infection, while there were no skin
      and soft-tissue infections among patients in the EGN coverage group. Nonetheless,
      this was not a significant difference (p = 0.345). In addition, the proportion of
      non-extremity infections was not significantly different between narrow and EGN
      regimen groups (11% and 15%, respectively). There were also no significant
      differences between the narrow and EGN regimen groups related to duration of
      hospitalization (median of 19 versus 20 d). Conclusion: Use of non-guideline
      directed EGN-based post-trauma antibiotic prophylaxis does not improve infectious
      outcomes nor does it shorten hospital stay.

PMID- 29447383
TI  - Super-resolution imaging identifies PARP1 and the Ku complex acting as DNA double
      strand break sensors.
AB  - DNA double-strand breaks (DSBs) are fatal DNA lesions and activate a rapid DNA
      damage response. However, the earliest stage of DSB sensing remains elusive.
      Here, we report that PARP1 and the Ku70/80 complex localize to DNA lesions
      considerably earlier than other DSB sensors. Using super-resolved fluorescent
      particle tracking, we further examine the relocation kinetics of PARP1 and the
      Ku70/80 complex to a single DSB, and find that PARP1 and the Ku70/80 complex are
      recruited to the DSB almost at the same time. Notably, only the Ku70/80 complex
      occupies the DSB exclusively in the G1 phase; whereas PARP1 competes with the
      Ku70/80 complex at the DSB in the S/G2 phase. Moreover, in the S/G2 phase, PARP1
      removes the Ku70/80 complex through its enzymatic activity, which is further
      confirmed by in vitro DSB-binding assays. Taken together, our results reveal
      PARP1 and the Ku70/80 complex as critical DSB sensors, and suggest that PARP1 may
      function as an important regulator of the Ku70/80 complex at the DSBs in the S/G2
      phase.

PMID- 29447386
TI  - Kick.it: The development of an evidence-based smoking cessation smartphone app.
AB  - Currently, the evidence for mobile health (mHealth) smoking cessation
      interventions is limited and heterogeneous, warranting the need for innovative
      rigorously developed solutions. The aim of this study was to describe the
      development of a smoking cessation smartphone application (app) developed using
      evidence-based principles. The app (Kick.it) was designed using the Intervention
      Mapping framework, incorporating an extensive literature review and qualitative
      study, in combination with the Behavioural Change Taxonomy v1, the Theoretical
      Domains Framework, and the Persuasive System Design framework. Kick.it provides
      quit smoking education, skills training, motivational content and self-regulation
      functionality for smokers, as well as their social support network. By logging
      cravings and cigarettes smoked, users will create their own smoking profile,
      which will be used to provide tailored interventions. It hosts a social network
      to allow 24/7 social support and provides in-app tools to help with urges to
      smoke. The app aims to motivate smokers to retry if they slip-up or relapse,
      allowing them to learn from previous smoking cessation attempts. Rather than
      basing the app on a singular behavioral change approach, Kick.it will use
      elements stemming from a variety of behavioral approaches by combining methods of
      multiple psychological theories. The use of best-practice intervention
      development frameworks in conjunction with evidence-based behavioral change
      techniques is expected to result in a smartphone app that has an optimal chance
      of helping people to quit smoking.

PMID- 29447388
TI  - Enhancing protein fold determination by exploring the complementary information
      of chemical cross-linking and coevolutionary signals.
AB  - Motivation: Elucidation of protein native states from amino acid sequences is a
      primary computational challenge. Modern computational and experimental
      methodologies, such as molecular coevolution and chemical cross-linking mass
      spectrometry allowed protein structural characterization to previously intangible
      systems. Despite several independent successful examples, data from these
      distinct methodologies have not been systematically studied in conjunction. One
      challenge of structural inference using coevolution is that it is limited to
      sequence fragments within a conserved and unique domain for which sufficient
      sequence datasets are available. Therefore, coupling coevolutionary data with
      complimentary distance constraints from orthogonal sources can provide additional
      precision to structure prediction methodologies. Results: In this work, we
      present a methodology to combine residue interaction data obtained from
      coevolutionary information and cross-linking/mass spectrometry distance
      constraints in order to identify functional states of proteins. Using a
      combination of structure-based models (SBMs) with optimized Gaussian-like
      potentials, secondary structure estimation and simulated annealing molecular
      dynamics, we provide an automated methodology to integrate constraint data from
      diverse sources in order to elucidate the native conformation of full protein
      systems with distinct complexity and structural topologies. We show that cross
      linking mass spectrometry constraints improve the structure predictions obtained
      from SBMs and coevolution signals, and that the constraints obtained by each
      method have a useful degree of complementarity that promotes enhanced fold
      estimates. Availability and implementation: Scripts and procedures to implement
      the methodology presented herein are available at
      https://github.com/mcubeg/DCAXL. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29447387
TI  - Ezh2 promotes clock function and hematopoiesis independent of histone
      methyltransferase activity in zebrafish.
AB  - EZH2 is a subunit of polycomb repressive complex 2 (PRC2) that silences gene
      transcription via H3K27me3 and was shown to be essential for mammalian liver
      circadian regulation and hematopoiesis through gene silencing. Much less,
      however, is known about how Ezh2 acts in live zebrafish. Here, we show that
      zebrafish ezh2 is regulated directly by the circadian clock via both E-box and
      RORE motif, while core circadian clock genes per1a, per1b, cry1aa and cry1ab are
      down-regulated in ezh2 null mutant and ezh2 morphant zebrafish, and either
      knockdown or overexpression of ezh2 alters locomotor rhythms, indicating that
      Ezh2 is required for zebrafish circadian regulation. In contrast to its canonical
      silencing function, zebrafish Ezh2 up-regulates these key circadian clock genes
      independent of histone methyltransferase activity by directly binding to key
      circadian clock proteins. Similarly, Ezh2 contributes to hematopoiesis by
      enhancing expression of hematopoietic genes such as cmyb and lck. Together, our
      findings demonstrate for the first time that Ezh2 acts in both circadian
      regulation and hematopoiesis independent of silencing PRC2.

PMID- 29447389
TI  - Survival of adults with systemic autoimmune rheumatic diseases and pulmonary
      arterial hypertension after lung transplantation.
AB  - Objectives: Pulmonary arterial hypertension (PAH) is a major cause of morbidity
      and mortality in adults with systemic autoimmune rheumatic diseases (ARDs). The
      aim of this study was to determine whether adults with ARDs and PAH on right
      sided heart catheterization (ARD-PAH) have increased mortality following lung
      transplantation compared with those with PAH not due to an ARD. Methods: We
      conducted a retrospective cohort study of 93 adults with ARD-PAH and 222 adults
      with PAH who underwent lung transplantation in the USA between 4 May 2005 and 9
      March 2015 using data from the United Network for Organ Sharing. We examined
      associations between diagnosis and survival after lung transplantation using
      stratified Cox models adjusted for potential confounding recipient factors.
      Results: Among adults undergoing lung transplantation in the USA, we did not
      detect a difference in the multivariable-adjusted mortality rate between those
      with ARD-PAH and those with PAH [hazard ratio 0.75 (95% CI 0.47, 1.19)].
      Conclusion: The presence of an ARD was not associated with increased mortality
      after lung transplantation in adults with PAH.

PMID- 29447390
TI  - Pold3 is required for genomic stability and telomere integrity in embryonic stem
      cells and meiosis.
AB  - Embryonic stem cells (ESCs) and meiosis are featured by relatively higher
      frequent homologous recombination associated with DNA double strand breaks (DSB)
      repair. Here, we show that Pold3 plays important roles in DSB repair, telomere
      maintenance and genomic stability of both ESCs and spermatocytes in mice. By
      attempting to generate Pold3 deficient mice using CRISPR/Cas9 or transcription
      activator-like effector nucleases, we show that complete loss of Pold3 (Pold3-/-)
      resulted in early embryonic lethality at E6.5. Rapid DNA damage response and
      massive apoptosis occurred in both outgrowths of Pold3-null (Pold3-/-)
      blastocysts and Pold3 inducible knockout (iKO) ESCs. While Pold3-/- ESCs were not
      achievable, Pold3 iKO led to increased DNA damage response, telomere loss and
      chromosome breaks accompanied by extended S phase. Meanwhile, loss of Pold3
      resulted in replicative stress, micronucleation and aneuploidy. Also, DNA repair
      was impaired in Pold3+/- or Pold3 knockdown ESCs. Moreover, Pold3 mediates DNA
      replication and repair by regulating 53BP1, RIF1, ATR and ATM pathways.
      Furthermore, spermatocytes of Pold3 haploinsufficient (Pold3+/-) mice with
      increasing age displayed impaired DSB repair, telomere shortening and loss, and
      chromosome breaks, like Pold3 iKO ESCs. These data suggest that Pold3 maintains
      telomere integrity and genomic stability of both ESCs and meiosis by suppressing
      replicative stress.

PMID- 29447392
TI  - Activity-dependent functions of non-electrical glial cells.
AB  - Electrical activity is essential for brain function. However, neurons, the
      electrically active cells, are less numerous than the non-electrical glial cells
      in the central nervous system. The non-electrical components modify the function
      of neural circuits, depending on the electrical neuronal activity, by wrapping
      synapses, myelinating axons and phagocytozing the neuronal components. Moreover,
      recent evidence has suggested that they contribute to neurological and
      psychiatric disease by regulating neuronal circuits, ultimately affecting their
      behaviour. In this review, we highlight the physiological functions of glial
      cells, particularly the electrical activity-dependent processes, to provide
      further insight into their role in brain function.

PMID- 29447391
TI  - Comparative analysis of epidermal differentiation genes of crocodilians suggests
      new models for the evolutionary origin of avian feather proteins.
AB  - The epidermis of amniotes forms a protective barrier against the environment and
      the differentiation program of keratinocytes, the main cell type in the
      epidermis, has undergone specific alterations in the course of adaptation of
      amniotes to a broad variety of environments and lifestyles. The epidermal
      differentiation complex (EDC) is a cluster of genes expressed at late stages of
      keratinocyte differentiation in both sauropsids and mammals. In the present study
      we identified and analyzed the crocodilian equivalent of the EDC. The gene
      complement of the EDC of both the American alligator and the saltwater crocodile
      were determined by comparative genomics, de novo gene prediction and
      identification of EDC transcripts in published transcriptome data. We found that
      crocodilians have an organization of the EDC similar to that of their closest
      living relatives, the birds, with which they form the clade Archosauria. Notable
      differences include the specific expansion of a subfamily of EDC genes in
      crocodilians and the loss of distinct ancestral EDC genes in birds.
      Identification and comparative analysis of crocodilian orthologs of avian feather
      proteins suggest that the latter evolved by cooption and sequence modification of
      ancestral EDC genes, and that the amplification of an internal highly cysteine
      enriched amino acid sequence motif gave rise to the feather component Epidermal
      Differentiation Cysteine Rich Protein (EDCRP) in the avian lineage. Thus,
      sequence diversification of EDC genes contributed to the evolutionary divergence
      of the crocodilian and avian integuments.

PMID- 29447393
TI  - Disruption of SPT23 results in increased heat sensitivity due to plasma membrane
      damage in Pichia pastoris.
AB  - The ability to adapt to environmental changes is a necessary strategy for cell
      survival. Spt23 is responsible for regulation of Delta-9 desaturase expression in
      Pichia pastoris. Disruption of SPT23 leads to a remarkable decrease in cellular
      unsaturated fatty acids. In this study, we found that deletion of SPT23 resulted
      in growth defects under high temperature culture conditions and heat treatment
      induced the expression of SPT23. By measuring expression changes of heat shock
      proteins, protein levels and cellular localization of Hsf1, it was revealed that
      the sensitivity of spt23Delta to high temperature was independent of the heat
      shock response. Addition of the osmotic stabilizer sorbitol can restore the
      growth defects of spt23Delta under heat conditions. In addition, loss of SPT23
      led to increased plasma membrane permeability, decreased plasma membrane
      integrity, depolarization, ergosterol synthesis defects and cell wall component
      disorder, which suggested that the sensitivity to heat treatment in spt23Delta
      was due to plasma membrane damage. Taken together, our results give new insights
      into the relationship between Spt23 and high temperature environmental stress.

PMID- 29447395
TI  - Characteristics and Outcomes of Coronavirus Infection in Children: The Role of
      Viral Factors and an Immunocompromised State.
AB  - Background: Immunocompromised children might be predisposed to serious infections
      from human coronaviruses (HCoVs), including strains OC43, NL63, HKU1, and 229E;
      however, the virologic and clinical features of HCoV infection in
      immunocompromised children have not been compared to those in
      nonimmunocompromised children. Methods: We retrospectively analyzed a cohort of
      children who presented to Seattle Children's Hospital and in whom HCoV was
      detected by a multiplex respiratory polymerase chain reaction assay of a nasal
      sample between October 2012 and March 2016. Lower respiratory tract disease
      (LRTD) was defined as possible or definite infiltrate seen in chest imaging, need
      for oxygen, or abnormal lung examination in conjunction with a physician
      diagnosis of LRTD. We used logistic regression modeling to evaluate risk factors
      for LRTD and LRTD that necessitated oxygen use (severe LRTD), including an
      immunocompromised state, in children with HCoV infection. Results: The median
      ages of 85 immunocompromised and 1152 nonimmunocompromised children with HCoV
      infection were 6.3 and 1.6 years, respectively. The prevalence of LRTD and of
      severe LRTD did not differ greatly between the immunocompromised and
      nonimmunocompromised patients (22% vs 26% [LRTD] and 15% vs 11% [severe LRTD],
      respectively); however, in a multivariable model, an immunocompromised state was
      associated with an increased likelihood of severe LRTD (adjusted odds ratio, 2.5
      [95% confidence interval, 1.2-4.9]; P = .01). Younger age, having an underlying
      pulmonary disorder, and the presence of respiratory syncytial virus were also
      associated with LRTD or severe LRTD in multivariable models. The risks of LRTD or
      severe LRTD did not differ among the children with different HCoV strains.
      Conclusions: The presence of a copathogen and host factors, including an
      immunocompromised state, were associated with increased risk for severe LRTD.
      Recognizing risk factors for severe respiratory illness might assist in risk
      stratification.

PMID- 29447394
TI  - Human La binds mRNAs through contacts to the poly(A) tail.
AB  - In addition to a role in the processing of nascent RNA polymerase III
      transcripts, La proteins are also associated with promoting cap-independent
      translation from the internal ribosome entry sites of numerous cellular and viral
      coding RNAs. La binding to RNA polymerase III transcripts via their common UUU
      3'OH motif is well characterized, but the mechanism of La binding to coding RNAs
      is poorly understood. Using electromobility shift assays and cross-linking
      immunoprecipitation, we show that in addition to a sequence specific UUU-3'OH
      binding mode, human La exhibits a sequence specific and length dependent poly(A)
      binding mode. We demonstrate that this poly(A) binding mode uses the canonical
      nucleic acid interaction winged helix face of the eponymous La motif, previously
      shown to be vacant during uridylate binding. We also show that cytoplasmic, but
      not nuclear La, engages poly(A) RNA in human cells, that La entry into polysomes
      utilizes the poly(A) binding mode, and that La promotion of translation from the
      cyclin D1 internal ribosome entry site occurs in competition with cytoplasmic
      poly(A) binding protein (PABP). Our data are consistent with human La functioning
      in translation through contacts to the poly(A) tail.

PMID- 29447397
TI  - Barriers and facilitators of diabetes services in Nepal: a qualitative
      evaluation.
AB  - For the past three decades, the burden of diabetes in Nepal has been steadily
      increasing, with an estimated 3% annual increase since the year 2000. Although
      the burden is increasing, the methods of addressing the challenge have remained
      largely unchanged. This study sought to assess the current state of diabetes
      services provided by health facilities and to identify the major barriers that
      people with diabetes commonly face in Nepal. For this qualitative study, we
      selected five health facilities of varying levels and locations. At each site, we
      employed three unique methods: a process evaluation of the diabetes treatment and
      prevention services available, in-depth interviews with patients and focus group
      discussions with community members without diabetes. We used thematic analysis to
      analyse the data. Our findings were organized into the five categories of the
      Ecological Model: Individual, Interpersonal, Organizational, Community and Public
      Policy. Sub-optimal knowledge and behaviors of patients often contributed to poor
      diabetes management, especially related to diet control, physical activity and
      initiation of drug treatment. Social support was often lacking. Organizational
      challenges included health provider shortages, long wait times, high patient
      loads and minimal time available to spend with patients, often resulting in
      incomprehensive care. Public policy challenges include limited services in rural
      settings and financial burden. The scarcity of financial and human resources for
      health in Nepal often results in the inability of the current healthcare system
      to provide comprehensive prevention and management services for chronic diseases.
      A multilevel, coordinated approach is necessary to address these concerns. In the
      short-term, adding community-based supplementary solutions outside of the
      traditional hospital-based model could help to increase access to affordable
      services.

PMID- 29447398
TI  - Secular Trends in the Physical Fitness of United States Army Infantry Units and
      Infantry Soldiers, 1976-2015.
AB  - Introduction: The purpose of this investigation was to examine changes over time
      in the physical fitness of the United States (US) Army infantry. A systematic
      review was conducted to identify and analyze articles and databases that reported
      on physical characteristics (height, weight, and body mass index) and/or Army
      Physical Fitness Test (APFT) scores of male infantrymen or men in infantry units.
      Materials and Methods: The National Library of Medicine's PubMed and the Defense
      Technical Information Center were searched using specific keywords. Reference
      lists of obtained articles, specific author searches, contact with authors, and
      secondary analysis of available databases enhanced the search. Studies and
      databases were selected if they involved infantry soldiers or soldiers in
      infantry units and provided a quantitative assessment of at least one physical
      characteristic or APFT measure. Average values for each measure were obtained,
      plotted by the year of data collection, and fitted to linear regression models.
      Results: Thirty-one articles and five available databases met the review criteria
      encompassing years 1976-2015. Regression analysis suggested a small temporal
      increase in height for infantry soldiers (2%) and soldiers in infantry units
      (1%). Body weight and body mass index increased over the period (9-15%) in both
      groups. APFT performance of infantry soldiers was generally higher than that of
      infantry units. There was little change in APFT performance over the period for
      infantry soldiers. For soldiers in infantry units, push-up performance changed
      little over time, whereas sit-up performance increased (8%) and two-mile run
      performance decreased (8%). Conclusion: Over the surveyed period, body weight and
      body mass index increased in US Army infantry soldiers and soldier in infantry
      units. Infantry soldier performance on the APFT appears to have been maintained
      over the period. For soldiers in infantry units, there has been a small
      improvement in sit-up performance, but lower two-mile run performance.

PMID- 29447396
TI  - RNA-DNA hybrids promote the expansion of Friedreich's ataxia (GAA)n repeats via
      break-induced replication.
AB  - Expansion of simple DNA repeats is responsible for numerous hereditary diseases
      in humans. The role of DNA replication, repair and transcription in the expansion
      process has been well documented. Here we analyzed, in a yeast experimental
      system, the role of RNA-DNA hybrids in genetic instability of long (GAA)n
      repeats, which cause Friedreich's ataxia. Knocking out both yeast RNase H
      enzymes, which counteract the formation of RNA-DNA hybrids, increased (GAA)n
      repeat expansion and contraction rates when the repetitive sequence was
      transcribed. Unexpectedly, we observed a similar increase in repeat instability
      in RNase H-deficient cells when we either changed the direction of transcription
      replication collisions, or flipped the repeat sequence such that the (UUC)n run
      occurred in the transcript. The increase in repeat expansions in RNase H
      deficient strains was dependent on Rad52 and Pol32 proteins, suggesting that
      break-induced replication (BIR) is responsible for this effect. We conclude that
      expansions of (GAA)n repeats are induced by the formation of RNA-DNA hybrids that
      trigger BIR. Since this stimulation is independent of which strand of the repeat
      (homopurine or homopyrimidine) is in the RNA transcript, we hypothesize that
      triplex H-DNA structures stabilized by an RNA-DNA hybrid (H-loops), rather than
      conventional R-loops, could be responsible.

PMID- 29447399
TI  - The Relationship Between Soldier Performance on the Two-Mile Run and the 20-m
      Shuttle Run Test.
AB  - Background: The 20-m shuttle run test (MSRT) is a common field test used to
      measure aerobic fitness in controlled environments. The U.S. Army currently
      assesses aerobic fitness with the two-mile run (TMR), but external factors may
      impact test performance. The aim of this study is to examine the relationship
      between the Army Physical Fitness Test TMR performance and the MSRT in military
      personnel. Methods: A group of 531 (403 males and 128 females) active duty
      soldiers (age: 24.0 +/- 4.1 years) performed the MSRT in an indoor facility.
      Heart rate was monitored for the duration of the test. Post-heart rate and age
      predicted maximal heart rate were utilized to determine near-maximal performance
      on the MSRT. The soldiers provided their most recent Army Physical Fitness Test
      TMR time (min). A Pearson correlation and multiple linear regression analyses
      were performed to examine the relationship between TMR time (min) and MSRT score
      (total number of shuttles completed). The study was approved by the Human Use
      Review Committee at the U.S. Army Research Institute of Environmental Medicine,
      Natick, Massachusetts. Findings: A significant, negative correlation exists
      between TMR time and MSRT score (r = -0.75, p < 0.001). Sex and MSRT score
      significantly predicted TMR time (adjusted R2 = 0.65, standard error of estimate
      = 0.97, p < 0.001) with a 95% ratio limits of agreement of +/-12.6%. The
      resulting equation is: TMR = 17.736-2.464 * (sex) - 0.050 * (MSRT) - 0.026 *
      (MSRT * sex) for predicted TMR time. Males equal zero, females equal one, and
      MSRT score is the total number of shuttles completed. Discussion: The MSRT is a
      strong predictor of the TMR and should be considered as a diagnostic tool when
      assessing aerobic fitness in active duty soldiers.

PMID- 29447400
TI  - Prevalence and Clinical Correlation of Superficial Fungal Foot Infection in Thai
      Naval Rating Cadets.
AB  - Background: Superficial fungal foot infection is one of the most important
      dermatological diseases currently affecting military personnel. Many Thai naval
      rating cadets are found to suffer from superficial fungal foot infections and
      their sequels. Objective: To investigate prevalence, potent risk factors,
      responding pathogens and clinical correlation of superficial fungal foot
      infection in Thai naval rating cadets training in Naval rating school, Sattahip,
      Thailand. Materials and Methods: This cross-sectional study was performed in
      August 2015. Validated structured questionnaire was used regarding information
      about behaviors and clinical symptoms. Quality of life was assessed by
      Dermatology Quality of Life Index (DLQI) questionnaire and clinical presentation
      demonstrated by Athlete's foot severity score (AFSS). Laboratory investigations
      including direct microscopic examination and fungal culture were performed and
      recorded. All of the participants were informed and asked for their consent.
      Results: A total of 788 Thai naval rating cadets with a mean age of 19 yr were
      enrolled. There were 406 (51.5%) participants suspected of fungal skin infection
      from questionnaire screening. After clinical examination, 303 participants
      (38.5%) were found to have foot lesions (AFSS >=1). Superficial fungal foot
      infection was diagnosed with microscopic examination and fungal culture in 57
      participants, giving a point prevalence of 7.2%. Tinea pedis was diagnosed in 54
      participants with the leading causative organism being Trichophyton
      mentagrophytes (52.8%). Other 3 participants were diagnosed as cutaneous
      candidiasis. Wearing combat shoes more than 8 h was found to be a predisposing
      factor (p = 0.029), taking a shower less than two times a day (p = 0.008), and
      wearing sandals during shower (p = 0.055) was found to be protective against
      infection. Most fungal feet infection cases noticed their feet abnormalities (p <
      0.001) including scales (p < 0.001), vesicles (p = 0.003) and maceration at
      interdigital web spaces (p < 0.001). Mean DLQI in superficial fungal foot
      infection cases was 3.35. Participants who had foot lesions (AFSS >=1) were
      concerned of their foots unpleasant odor demonstrated significantly higher mean
      DLQI than those without odor (4.2 vs. 2.28; p < 0.001). Conclusion: Superficial
      fungal foot infection is found as 7.2% of naval rating cadets. Wearing combat
      shoes more than 8 h was found to be a predisposing factor. In addition to skin
      manifestations including scales, vesicles, and maceration, superficial fungal
      foot infection also exhibited an unpleasant foot odor which affected quality of
      life. Self-foot-examination and life style modification should be promoted to
      prevent fungal infection.

PMID- 29447401
TI  - RaMWAS: fast methylome-wide association study pipeline for enrichment platforms.
AB  - Motivation: Enrichment-based technologies can provide measurements of DNA
      methylation at tens of millions of CpGs for thousands of samples. Existing tools
      for methylome-wide association studies cannot analyze datasets of this size and
      lack important features like principal component analysis, combined analysis with
      SNP data and outcome predictions that are based on all informative methylation
      sites. Results: We present a Bioconductor R package called RaMWAS with a full set
      of tools for large-scale methylome-wide association studies. It is free, cross
      platform, open source, memory efficient and fast. Availability and
      implementation: Release version and vignettes with small case study at
      bioconductor.org/packages/ramwas Development version at
      github.com/andreyshabalin/ramwas. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29447402
TI  - Intraoperative Endotracheal Cuff Pressure Study: How Education and Availability
      of Manometers Help Guide Safer Pressures.
AB  - Introduction: Endotracheal intubation is a medical procedure that is often
      indicated in both the perioperative and critical care environments. Cuffed
      endotracheal tubes (ETT) allow for safer and more efficient delivery of positive
      pressure ventilation, as well as create a barrier to reduce the risk of micro
      aspiration and anesthetic pollution in the operating room environment. Over
      inflation of the endotracheal cuff can lead to serious and harmful sequelae. This
      study aimed to assess if departmental education paired with ready access to a
      manometer to assess cuff pressure would result in an improvement in the
      proportion of ETT cuff pressures in the goal range. Materials and Methods: A
      quality improvement study was conducted at the San Antonio Military Medical
      Center (SAMMC; Department of Defense hospital in San Antonio, TX). The initiative
      was divided into three key periods: pre-implementation, implementation, and post
      implementation. During the pre-implementation period, ETT cuff pressures were
      obtained to assess the baseline state of ETT cuff pressures for patients in the
      operating room; the proportion of in-range (20-30 cmH2O) pressures was
      calculated. During the implementation phase, operating rooms were equipped with
      manometers and anesthesia departmental education was performed regarding the use
      of the manometers. Three months later, post-implementation cuff pressures were
      measured in the OR, and the proportion of in-range pressures was again
      calculated. Results: The pre-implementation data showed an average cuff pressure
      of 48.92 cmH2O and a median of 38.5 cmH2O. Of the 100 pre-implementation
      pressures, 20 were in the goal range. Post-implementation data had an average
      cuff pressure of 41.96 cmH2O and a median of 30 cmH2O. A chi-squared test of
      pressures in the safe range from the pre-implementation versus post
      implementation values yielded a highly significant p-value of 0.0003. Conclusion:
      The data from this study clearly demonstrated a statistically significant
      improvement in the proportion of in-range cuff pressures following the quality
      improvement initiative. This study supports the use of department-wide education
      and the availability of manometers in each OR to yield safer cuff pressures for
      intubated patients. This study did not aim to determine an optimal ETT cuff
      pressure, but utilized data already available to determine a safe cuff pressure.
      Further research needs to be performed to assess whether routine monitoring of
      cuff pressure results in improved patient outcomes.

PMID- 29447403
TI  - Assessment of data quality and reporting systems for underserved populations: the
      case of integrated community case management programs in Nigeria.
AB  - Decision makers are searching for reliable data and best practices to support the
      implementation and scale-up of the integrated community case management (iCCM)
      programs in underserved areas to reduce under-five mortality in low-income
      countries. This study assesses data quality and reporting systems of the World
      Health Organization supported Rapid Access Expansion program implementing iCCM in
      Abia and Niger States, Nigeria. This cross-sectional study used data from 16
      primary health facilities in both states. Data were collected through review of
      registers and monthly summary reports of 140 community-oriented resource persons
      (CORPs), assessments of the five dimensions of the data reporting systems and 46
      key informant interviews with stakeholders. Data quality was assessed by
      availability, completeness and consistency. Each component of the reporting
      system was assessed on a 3-point scale (weak, satisfactory and strong). Results
      show that both the structure, functions and capabilities, as well as data
      collection and reporting tools dimensions of the reporting system were strong,
      scoring (2.80, 2.73) for Abia and (2.88, 2.75) for Niger, respectively. Data
      management processes and links with national reporting system components scored
      low 2 s, indicating fair strength. Data availability, completeness and
      consistency were found to be good, an indication of adequate training and
      supervision of CORPs and community health extension workers. Indicator
      definitions and reporting guidelines were the weakest dimension of the system due
      to lack of data reporting guidelines in both states. In conclusion, the results
      indicate satisfactory data reporting systems and good quality data during early
      implementation of iCCM programs in the two states. Hence, countries planning to
      adopt and implement iCCM programs should first develop structures, establish
      national standardized tools for collecting and reporting data, provide for
      adequate training and supervision of community health workers and develop
      reporting guidelines for all reporting levels to ensure data quality.

PMID- 29447404
TI  - Personal network characteristics and body mass index: the role of education among
      Black Americans.
AB  - Background: Personal (i.e. egocentric) network characteristics are associated
      with health outcomes, including overweight and obesity. Previous research
      suggests educational attainment may interact with network characteristics to
      buffer these relationships. Limited research has examined the personal network
      characteristics of Black Americans, who have increased risk of overweight and
      obesity. The purpose of the current study was to examine associations between
      network characteristics and body mass index (BMI), and whether educational
      attainment modified these associations among Black Americans. Methods: In 2014,
      using respondent-driven sampling, we recruited 430 adult residents of eight low
      income neighborhoods in Greenville, SC. Self-administered questionnaires assessed
      structural and compositional characteristics (i.e. size, density) of respondents'
      personal networks, socio-demographic characteristics, and health-related
      behaviors and conditions. Multilevel regression models with robust sandwich
      estimation accounted for clustering within respondent chains. Results: Among
      Black adults overall, network density-the number of connections among network
      members-was positively associated with BMI. Higher education moderated this
      relationship; among Black adults with a college degree, higher network density
      was inversely associated with BMI. Conclusions: Our data suggest low educational
      attainment may reflect more homogenous and less resourceful networks. Multiple
      pathways are discussed for how education interacts with network density on BMI
      among Black Americans.

PMID- 29447405
TI  - The representation of vulnerable populations in quality improvement studies.
AB  - Purpose: A mapping review to quantify representation of vulnerable populations,
      who suffer from disparity and often inequitable healthcare, in quality
      improvement (QI) research. Data sources: Studies published in 2004-2014 inclusive
      from Medline, Embase and Cochrane databases for English language research with
      the terms 'quality improvement' or 'quality control' or 'QI' and 'plan-do-study
      act' or 'PDSA' in the years 2004-2014 inclusively. Study selection: Published
      clinical research that was a QI-themed, as identified by its declared search
      terms, MESH terms, abstract or title. Data extraction: Three reviewers identified
      the eligible studies independently. Excluded were publications that were not
      trials, evaluations or analyses. Results of data synthesis: Of 2039 results, 1660
      were eligible for inclusion. There were 586 (33.5%) publications that targeted a
      specific vulnerable population: children (184, 10.54%), mental health patients
      (125, 7.16%), the elderly (100, 5.73%), women (57, 3.27%), the poor (30, 1.72%),
      rural residents (29, 1.66%), visible minorities (27, 1.55%), the terminally ill
      (17, 0.97%), adolescents (16, 0.92%) and prisoners (1 study). Seventy-four
      articles targeted two or more vulnerable populations, and 11 targeted three
      population categories. On average, there were 158 QI research studies published
      per year, increasing from 69 in 2004 to 396 in 2014 (R2 = 0.7, P < 0.001). The
      relative representation of vulnerable populations had a mean of 33.58% and was
      stable over the time period (standard deviation (SD) = 5.9%, R2 = 0.001). Seven
      countries contributed to over 85% of the publications targeting vulnerable
      populations, with the USA contributing 62% of the studies. Conclusions: Over 11
      years, there has been a marked increase in QI publications. Roughly one-third of
      all published QI research is on vulnerable populations, a stable proportion over
      time. Nevertheless, some vulnerable populations are under-represented. Increased
      education, resources and attention are encouraged to improve the health of
      vulnerable populations through focused QI initiatives.

PMID- 29447406
TI  - Using structural equation modelling to jointly estimate maternal and fetal
      effects on birthweight in the UK Biobank.
AB  - Background: To date, 60 genetic variants have been robustly associated with
      birthweight. It is unclear whether these associations represent the effect of an
      individual's own genotype on their birthweight, their mother's genotype, or both.
      Methods: We demonstrate how structural equation modelling (SEM) can be used to
      estimate both maternal and fetal effects when phenotype information is present
      for individuals in two generations and genotype information is available on the
      older individual. We conduct an extensive simulation study to assess the bias,
      power and type 1 error rates of the SEM and also apply the SEM to birthweight
      data in the UK Biobank study. Results: Unlike simple regression models, our
      approach is unbiased when there is both a maternal and a fetal effect. The method
      can be used when either the individual's own phenotype or the phenotype of their
      offspring is not available, and allows the inclusion of summary statistics from
      additional cohorts where raw data cannot be shared. We show that the type 1 error
      rate of the method is appropriate, and that there is substantial statistical
      power to detect a genetic variant that has a moderate effect on the phenotype and
      reasonable power to detect whether it is a fetal and/or a maternal effect. We
      also identify a subset of birthweight-associated single nucleotide polymorphisms
      (SNPs) that have opposing maternal and fetal effects in the UK Biobank.
      Conclusions: Our results show that SEM can be used to estimate parameters that
      would be difficult to quantify using simple statistical methods alone.

PMID- 29447407
TI  - The Feasibility of Venovenous ECMO at Role-2 Facilities in Austere Military
      Environments.
AB  - Introduction: Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been
      gaining use to bridge the recovery from acute respiratory distress syndrome
      (ARDS) refractory to conventional treatment. However, these interventions are
      often limited to higher echelons of military care. We present a case of lung
      salvage from severe ARDS in an Afghani soldier with VV-ECMO at a Role-2 (R2)
      facility in an austere military environment in Afghanistan. Case: A 25-year-old
      Afghani soldier presented to an R2 facility with blast lung injury and multiple
      penetrating injuries following an explosion. The patient underwent immediate
      damage control laparotomy. The abdomen was left open for subsequent washouts and
      ongoing resuscitation. Due to his ineligibility for evacuation and worsening
      ARDS, despite 5 d of conventional ventilation strategies, he was started on VV
      ECMO. The patient had immediate improvements in oxygenation, which continued for
      10 d. Moreover, he underwent three transportations to the operating room without
      accidental decannulation or disruption of the VV-ECMO device. Despite significant
      improvements, the patient expired on postoperative day 15, due to an overwhelming
      intra-abdominal sepsis. Conclusion: As future advancements are sought, VV-ECMO
      may become a consideration for casualties with severe ARDS at the point of injury
      and at lower echelons of military care.

PMID- 29447409
TI  - Surgical Duration and Potential Bias Can Affect Analgesic Outcomes Following
      Dexamethasone Use in Peripheral Nerve Blocks.

PMID- 29447408
TI  - Survival advantage of planned haemodialysis over peritoneal dialysis: a cohort
      study.
AB  - Background: Previous studies comparing the outcomes in haemodialysis (HD) with
      those in peritoneal dialysis (PD) have yielded conflicting results. Methods: The
      aim of the study was to compare the survival of planned HD versus PD patients in
      a cohort of adult incident patients who started renal replacement therapy (RRT)
      between 2006 and 2008 in the nationwide REIN registry (Reseau Epidemiologie et
      Information en Nephrologie). Patients who started RRT in emergency or stopped RRT
      within 2 months were excluded. Adjusted Cox models, propensity score matching and
      marginal structural models (MSMs) were used to compensate for the lack of
      randomization and provide causal inference from longitudinal data with time
      dependent treatments and confounders including transplant censorship, modality
      change over time and time-varying covariates. Results: Among a total of 13 767
      dialysis patients, 13% were on PD at initiation of RRT and 87% were on HD. The
      median survival times were 53.5 months or 4.45 years and 38.6 months or 3.21
      years for patients starting on HD and PD, respectively. Regardless of the model
      used, there was a consistent advantage in terms of survival for HD patients:
      hazard ratio (HR) 0.76 [95% confidence interval (95% CI) 0.69-0.84] with the Cox
      model using propensity score; HR 0.67 (95% CI 0.62-0.73) in the Cox model with
      censorship for each treatment change; and HR 0.82 (95% CI 0.69-0.97) with MSMs.
      However, MSMs tended to reduce the survival gap between PD and HD patients.
      Conclusion: This large cohort study using various statistical methods to minimize
      the bias appears to demonstrate a better survival in planned HD than in PD.

PMID- 29447410
TI  - Practical recommendations for the evaluation of improvement initiatives.
AB  - A lack of clear guidance for funders, evaluators and improvers on what to include
      in evaluation proposals can lead to evaluation designs that do not answer the
      questions stakeholders want to know. These evaluation designs may not match the
      iterative nature of improvement and may be imposed onto an initiative in a way
      that is impractical from the perspective of improvers and the communities with
      whom they work. Consequently, the results of evaluations are often controversial,
      and attribution remains poorly understood. Improvement initiatives are iterative,
      adaptive and context-specific. Evaluation approaches and designs must align with
      these features, specifically in their ability to consider complexity, to evolve
      as the initiative adapts over time and to understand the interaction with local
      context. Improvement initiatives often identify broadly defined change concepts
      and provide tools for care teams to tailor these in more detail to local
      conditions. Correspondingly, recommendations for evaluation are best provided as
      broad guidance, to be tailored to the specifics of the initiative. In this paper,
      we provide practical guidance and recommendations that funders and evaluators can
      use when developing an evaluation plan for improvement initiatives that seeks to:
      identify the questions stakeholders want to address; develop the initial program
      theory of the initiative; identify high-priority areas to measure progress over
      time; describe the context the initiative will be applied within; and identify
      experimental or observational designs that will address attribution.

PMID- 29447412
TI  - Service Models for Urgent and Emergency Psychiatric Care: An Overview.
AB  - There is variation in the way mental health services respond to urgent and
      emergency presentations, with few evidence-based models reported in the
      literature, and no agreed on best practice models. To inform the development of
      urgent and emergency psychiatric care models, a literature review was performed.
      The review sought to identify strengths and critiques of varying models, evidence
      gaps, and areas for future research. After review, significant variation was
      found in the design and scope of urgent and emergency care models. Most models
      are either community or hospital based, with few integrated models that span
      community and hospital care. The development of integrated models has the
      potential to reduce service duplication and support a shift toward provision of
      least restrictive care. The overall evidence base of urgent and emergency care
      models is limited, with few studies in the area, and there is a need for further
      research. [Journal of Psychosocial Nursing and Mental Health Services, 56(8), 23
      30.].

PMID- 29447411
TI  - The assessment of nailfold capillaries: comparison of dermoscopy and nailfold
      videocapillaroscopy.

PMID- 29447413
TI  - Effects of a Staff Training Intervention on Seclusion Rates on an Adult Inpatient
      Psychiatric Unit.
AB  - The current article presents the effects of a 90-minute staff training
      intervention aimed at reducing inpatient psychiatric seclusion rates through
      strengthened staff commitment to seclusion alternatives and improved de
      escalation skills. The intervention occurred at an 18-bed adult inpatient
      psychiatric unit whose seclusion rates in 2015 were seven times the national
      average. Although the project's primary outcome compared patient seclusion rates
      before and after the intervention, anonymous staff surveys measured several
      secondary outcomes. Seclusion rates were reduced from a 6-month pre-intervention
      average of 2.95 seclusion hours per 1,000 patient hours to a 6-month post
      intervention average of 0.29 seclusion hours per 1,000 patient hours, a 90.2%
      reduction. Completed staff surveys showed significant staff knowledge gains, non
      significant changes in staff attitudes about seclusion, non-significant changes
      in staff de-escalation skill confidence, and use of the new resource sheet by
      only 17% of staff. The key study implication is that time-limited, focused staff
      training interventions can have a measurable impact on reducing inpatient
      seclusion rates. [Journal of Psychosocial Nursing and Mental Health Services,
      56(6), 23-30.].

PMID- 29447414
TI  - Women With Dissociative Identity Disorder Who Experience Intimate Partner
      Violence.
AB  - Women with dissociative identity disorder (DID) are significantly more likely
      than other women to experience intimate partner violence (IPV). The purpose of
      this qualitative investigation was to explicate the experiences of women with DID
      who experience IPV and describe how they cope. Grounded theory was used to
      conduct this investigation. Purposive sampling was used to recruit participants
      (N = 5) for face-to-face, semi-structured interviews. Verbatim transcripts were
      coded and categorized, and reflective memos were developed to explicate
      substantive categories. Women with DID used coping strategies that were
      consistent with their diagnoses, such as switching and dissociating. These coping
      mechanisms reflect past self-preservation strategies that were developed in
      association with severe childhood maltreatment. Women with DID who experienced
      IPV sought to mitigate and safeguard themselves from danger using strategies they
      developed as maltreated children. Nurses can use these findings to better
      recognize and understand the motivations and behaviors of women with DID who
      experience IPV. [Journal of Psychosocial Nursing and Mental Health Services,
      56(5), 26-32.].

PMID- 29447415
TI  - Motivational Interviewing to Increase Outpatient Attendance for Adolescent
      Psychiatric Patients.
AB  - Motivational interviewing (MI) is a therapeutic technique that has been
      demonstrated to increase adherence to various treatment regimens. Nonattendance
      at outpatient appointments is associated with read-mission to psychiatric
      hospitals. The purpose of the current study was to examine the effectiveness of
      MI in promoting treatment adherence and increasing pediatric attendance rates at
      patients' first follow-up appointment after inpatient admission. A sample of 111
      patients discharged from one of two child and adolescent units at an urban,
      inpatient psychiatric hospital in Southwestern Pennsylvania participated in the
      MI discharge process. Compared to hospital population data from 1 month prior to
      the current study, the MI discharge process demonstrated an increase of
      approximately 10% in attendance at the scheduled follow-up appointments and a
      decrease of approximately 4% in cancellations and no-show appointments. It was
      concluded that particularly for adolescents, MI may be a valuable treatment
      approach grounded in partnerships with health care providers, patients, and
      families to enhance outpatient appointment attendance. [Journal of Psychosocial
      Nursing and Mental Health Services, 56(6), 31-35.].

PMID- 29447416
TI  - Managing Opioid Use Disorder and Co-Occurring Posttraumatic Stress Disorder Among
      Veterans.
AB  - Support and safety measures are essential for Veterans admitted to acute
      psychiatric units with co-occurring posttraumatic stress disorder (PTSD) and
      opioid use disorder (OUD) to avoid unpleasant withdrawal symptoms. A human
      patient simulator was used to train clinicians to recognize opioid withdrawal
      symptoms. Clinicians were educated to assess for opioid withdrawal symptoms using
      the Clinical Opiate Withdrawal Scale. Knowledge was evaluated via pre/posttest.
      All participants' (N = 12) posttest scores improved. Participants self-rated
      their perception of clinical knowledge and practice skills as higher
      postintervention. Veterans indicated decreased concern about opioid withdrawal
      symptoms and increased perception that symptoms were adequately evaluated and
      treated by clinicians. Overall, the intervention appeared to enhance the
      provision of quality care in Veterans with OUD and co-occurring PTSD on an acute
      inpatient psychiatric unit. [Journal of Psychosocial Nursing and Mental Health
      Services, 56(6), 36-42.].

PMID- 29447418
TI  - Woman With Rare Cause of Rectal Bleeding.

PMID- 29447417
TI  - Primary Central Nervous System Lymphoma-PART 1: Epidemiology, Diagnosis, Staging,
      and Prognosis.
AB  - Primary central nervous system (CNS) lymphoma is a rare CNS neoplasm. Its highest
      incidence is in the elderly and the immunocompromised. The initial steps in
      establishing a diagnosis involve CNS imaging. Familiarity with the clinical
      presentation is important in order to limit the risk of a nondiagnostic biopsy.
      In addition to confirming the diagnosis, it is wise to evaluate for extra-CNS
      disease. There are important differences in the presentation and evaluation of
      immunocompetent patients and those of immunocompromised patients; we will
      delineate these in this review. Appropriate initial clinical evaluations
      facilitate optimal therapeutic management for patients with primary CNS lymphoma.
      This is of particular importance because primary CNS lymphoma is a potentially
      curable disease, despite the high likelihood of recurrence.

PMID- 29447419
TI  - Fear of Cancer Recurrence: A Practical Guide for Clinicians.
AB  - With increasing cancer survival, fear of cancer recurrence (FCR) is becoming a
      prominent clinical issue. FCR is prevalent, distressing, and long-lasting, and
      can negatively impact patients' quality of life, use of health services, and
      adherence to follow-up recommendations. Novel targeted therapies may increase
      risk of FCR because of longer treatment duration and follow-up, increased
      prognostic precision, and omission of treatment based on genomic status.
      Oncologists can assess and screen for FCR using validated measures; provide
      adequate information about prognosis, signs and symptoms of recurrence, and
      behavioral strategies for risk reduction and follow-up; and warn patients and
      families that FCR may be an issue in survivorship. It is important to normalize
      FCR and encourage patients to discuss it if it is a concern. Patients with severe
      FCR should be referred to psycho-oncology staff, who can apply some of the novel
      psychotherapeutic interventions that have emerged to address this condition.

PMID- 29447420
TI  - Point: Weighing the Risks and Benefits of Neoadjuvant Therapy in Resectable
      Pancreatic Cancer. Early, Aggressive Neoadjuvant Therapy Is Appropriate in
      Selected Patients.

PMID- 29447421
TI  - Counterpoint: Weighing the Risks and Benefits of Neoadjuvant Therapy in
      Resectable Pancreatic Cancer. Neoadjuvant Therapy Should Not Be Used as Part of
      Standard Clinical Practice.

PMID- 29447422
TI  - Improving Childhood Cancer Survivor Care Through Web-Based Platforms.
AB  - Survivors of childhood cancer are at increased risk for late effects of cancer
      therapy, but evidence suggests that adherence to follow-up care is suboptimal.
      Here, we review the barriers to adherence, including those unique to childhood
      cancer survivors, and the rationale for distribution of a survivorship care plan.
      We also discuss advantages and potential limitations of delivering survivorship
      care plans via web-based platforms, and describe the unique features of one of
      these platforms, Passport for Care. A baseline survey directed toward survivors
      and conducted through Passport for Care found that a significant proportion of
      survivors are unaware of their specific health risks resulting from cancer and
      its treatment, and compared with their parents, are less afraid of the risks of
      recurrence and of cancer therapy-associated late effects (n = 528). Web-based
      platforms such as Passport for Care have enormous potential for improving access
      to health information, as well as for enhancing patient, family caregiver, and
      healthcare provider awareness of both risks of late effects and recommended
      surveillance. Results from this survey also suggest the potential utility of
      leveraging these tools to conduct additional research on consenting survivors.

PMID- 29447423
TI  - NK cells inhibit anti-Mycobacterium bovis BCG T cell responses and aggravate
      pulmonary inflammation in a direct lung infection mouse model.
AB  - Tuberculosis remains a threat to public health. The major problem for curing this
      disease is latent infection, of which the underlying mechanisms are still not
      fully understood. Previous studies indicate that natural killer (NK) cells do not
      play a role in inhibiting the growth of Mycobacterium tuberculosis in the lung,
      and recent studies have revealed that NK cells regulate the adaptive immunity
      during mycobacterial infection. By using a mouse model of direct lung infection
      with Mycobacterium bovis bacillus Calmette-Guerin (BCG), we found that the
      presence of NK cells postponed the priming and activation of T cells after BCG
      infection. In addition, depletion of NK cells before infection alleviated
      pulmonary pathology. Further studies showed that NK cells lysed BCG-infected
      macrophages in an NKG2D dependent manner. Thus, NK cells did not play a direct
      role in control BCG, but aggravated the pulmonary inflammation and impaired anti
      BCG T cell immunity, likely through killing BCG-infected macrophages. Our results
      may have important implications for the design of immune therapy to treat
      tuberculosis.

PMID- 29447425
TI  - Response to: Association between duration of oral contraceptive use and risk of
      hypertension: A meta-analysis: Methodological and statistical issues.

PMID- 29447424
TI  - Experimental and Theoretical Identification of the Origin of Magnetic Anisotropy
      in Intermediate Spin Iron(III) Complexes.
AB  - The complexes [FeLN2S2 X] [in which LN2S2 =2,2'-(2,2'-bipryridine-6,6'
      diyl)bis(1,1'-diphenylethanethiolate) and X=Cl, Br and I], characterized
      crystallographically earlier and here (Fe(L)Br), reveal a square pyramidal
      coordinated FeIII ion. Unusually, all three complexes have intermediate spin
      ground states. Susceptibility measurements, powder cw X- and Q-band EPR spectra,
      and zero-field powder Mossbauer spectra show that all complexes display distinct
      magnetic anisotropy, which has been rationalized by DFT calculations.

PMID- 29447426
TI  - A coiled-coil protein is required for coordination of karyokinesis and
      cytokinesis in Toxoplasma gondii.
AB  - Toxoplasma gondii is a unicellular eukaryotic pathogen that belongs to the
      Apicomplexa phylum, which encompasses some of the deadliest pathogens of medical
      and veterinary importance. The centrosome is key to the organisation and
      coordination of the cell cycle and division of apicomplexan parasites. The T.
      gondii centrosome possesses a particular bipartite structure (outer and inner
      cores). One of the main roles of the centrosome is to ensure proper coordination
      of karyokinesis. However, how these 2 events are coordinated is still unknown in
      T. gondii, for which the centrosome components are poorly described. To gain more
      insights into the biology and the composition of the T. gondii centrosome, we
      characterised a protein that resides at the interface of the outer and inner core
      centrosomes. TgCep530 is a large coiled-coil protein with an essential role in
      the survival of the parasite. Depletion of this protein leads to the accumulation
      of parasites lacking nuclei and disruption of the normal cell cycle. Lack of
      TgCep530 results in a discoordination between the nuclear cycle and the budding
      cycle that yields fully formed parasites without nuclei. TgCep530 has a crucial
      role in the coordination of karyokinesis and cytokinesis.

PMID- 29447427
TI  - Vestibulo-ocular reflex gain values in the suppression head impulse test of
      healthy subjects.
AB  - OBJECTIVE: To assess whether there are differences in vestibulo-ocular reflex
      (VOR) gain for suppression head impulse (SHIMP) and head impulse (HIMP) video
      head impulse test paradigms, and if so, what are their causes. METHODS:
      Prospective multicenter observational double-blind nonrandomized clinical study
      was performed by collecting 80 healthy subjects from four reference hospitals.
      SHIMP data was postprocessed to eliminate impulses in which early SHIMP saccades
      were detected. Differences between HIMP and SHIMP VOR gain values were
      statistically evaluated. Head impulse maximum velocity, gender, age, direction of
      impulse, and hospital center were considered as possible influential factors.
      RESULTS: A small significant statistical difference between HIMP and SHIMP VOR
      gain values was found on repeated measures analysis of variance (-0.05 +/- 0.006,
      P < 0.001). Optimized linear model showed a significant influence of age variable
      on the observed differences for HIMP and SHIMP gain values and did not find
      influence between gain values differences and maximum head impulse velocity. Both
      HIMP and SHIMP VOR gain values were significant lower (-0.09, P < 0.001) when the
      impulses were performed to the left side. CONCLUSION: We had observed a
      difference in SHIMP and HIMP gain values not adequately explained by known gain
      modification factors. The persistence of this slight but significant difference
      indicates that there are more factors causing lower SHIMP VOR gain values. This
      difference must to be considered in further studies as well as in the clinical
      SHIMP testing protocols. We hypothesized that VOR phasic response inhibition
      could be the underlying cause of this difference. LEVEL OF EVIDENCE: 2b.
      Laryngoscope, 128:2383-2389, 2018.

PMID- 29447428
TI  - UV-B radiation delays flowering time through changes in the PRC2 complex activity
      and miR156 levels in Arabidopsis thaliana.
AB  - UV-B is a high-energy component of the solar radiation perceived by the plant and
      induces a number of modifications in plant growth and development, including
      changes in flowering time. However, the molecular mechanisms underlying these
      changes are largely unknown. In the present work, we demonstrate that Arabidopsis
      plants grown under white light supplemented with UV-B show a delay in flowering
      time, and this developmental reprogramming is mediated by the UVR8 photoreceptor.
      Using a combination of gene expression analyses and UV-B irradiation of different
      flowering mutants, we gained insight into the pathways involved in the observed
      flowering time delay in UV-B-exposed Arabidopsis plants. We provide evidence that
      UV-B light downregulates the expression of MSI1 and CLF, two of the components of
      the polycomb repressive complex 2, which in consequence drives a decrease in
      H3K27me3 histone methylation of MIR156 and FLC genes. Modification in the
      expression of several flowering time genes as a consequence of the decrease in
      the polycomb repressive complex 2 activity was also determined. UV-B exposure of
      flowering mutants supports the involvement of this complex in the observed delay
      in flowering time, mostly through the age pathway.

PMID- 29447429
TI  - Arterial stiffness and subendocardial viability ratio in patients with peripheral
      arterial disease.
AB  - Arterial stiffening is a hallmark of the aging process and atherosclerosis,
      including peripheral arterial disease (PAD). We investigated the associations
      between carotid-femoral pulse wave velocity (c-fPWV), augmentation index
      corrected for heart rate (Aix@HR75), ankle brachial index (ABI), and
      subendocardial viability ratio (SEVR), an indicator of cardiac perfusion. The c
      fPWV, Aix@HR75, and SEVR was estimated using applanation tonometry. The ankle
      systolic pressure measurements for the calculation of the ABI were obtained using
      an 8-mHz Doppler probe. The study group included 555 subjects, mean age 63 +/- 11
      years (248 PAD (ABI < 1.0), and 307 non-PAD (ABI >= 1.0 <= 1.3). After the
      stepwise selection process in both PAD and non-PAD patients SEVR was not related
      to c-fPWV and ABI (P = .154; P = .156) and (P = .101; P = .402), respectively. In
      PAD patients, SEVR was negatively related to Aix@HR75 (P < .0001) and aortic PP
      (P = .0005). In conclusion, arterial stiffness is associated with non-invasive
      indices of myocardial perfusion in PAD patients, suggesting a potential
      pathophysiological link for increased cardiovascular events.

PMID- 29447431
TI  - Sulfur Hydrogen Bonding in Isolated Monohydrates: Furfuryl Mercaptan versus
      Furfuryl Alcohol.
AB  - The hydrogen bonds involving sulfur in the furfuryl mercaptan monohydrate are
      compared with the interactions originating from the hydroxyl group in furfuryl
      alcohol. The dimers with water were created in a supersonic jet expansion and
      characterized using microwave spectroscopy and supporting molecular orbital
      calculations. In furfuryl alcohol-water, a single isomer is observed, in which
      the water molecule forms an insertion complex with two simultaneous hydrogen
      bonds to the alcohol (O-H???Ow ) and the ring oxygen (Ow -H???Or ). When the
      alcohol is replaced by a thiol group in furfuryl mercaptan-water, two isomers are
      observed, with the thiol group preferentially behaving as proton donor to water.
      The first isomer is topologically equivalent to the alcohol analog but the
      stronger hydrogen bond is now established by water and the ring oxygen, assisted
      by a thiol S-H???Ow hydrogen bond. In the second isomer the sulfur group accepts
      a proton from water, forming a Ow -H???S hydrogen bond. Binding energies for the
      mercaptan-water dimer are predicted around 12 kJ mol-1 weaker than in the alcohol
      hydrate (B3LYP-D3(BJ)). The non-covalent interactions in the furfuryl dimers are
      dominantly electrostatic according to a SAPT(0) energy decomposition, but with
      increasing dispersion components in the mercaptan dimers, which are larger for
      the isomer with the weaker Ow -H???S interaction.

PMID- 29447432
TI  - Association between duration of oral contraceptive use and risk of hypertension:
      A meta-analysis, methodological and statistical issues.

PMID- 29447430
TI  - Aucubin protects against pressure overload-induced cardiac remodelling via the
      beta3 -adrenoceptor-neuronal NOS cascades.
AB  - BACKGROUND AND PURPOSE: Aucubin, the predominant component of Eucommia ulmoides
      Oliv., has been shown to have profound effects on oxidative stress. As oxidative
      stress has previously been demonstrated to contribute to acute and chronic
      myocardial injury, we tested the effects of aucubin on cardiac remodelling and
      heart failure. EXPERIMENTAL APPROACH: Initially, H9c2 cardiomyocytes and neonatal
      rat cardiomyocytes pretreated with aucubin (1, 3, 10, 25 and 50 MUM) were
      challenged with phenylephrine. Secondly, the transverse aorta was constricted in
      C57/B6 and neuronal NOS (nNOS)-knockout mice, then aucubin (1 or 5 mg.kg-1 body
      weight day-1 ) was injected i.p. for 25 days. Hypertrophy was evaluated by
      assessing morphological changes, echocardiographic parameters, histological
      analyses and hypertrophic markers. Oxidative stress was evaluated by examining
      ROS generation, oxidase activity and NO generation. NOS expression was determined
      by Western blotting. KEY RESULTS: Aucubin effectively suppressed cardiac
      remodelling; in mice, aucubin substantially inhibited pressure overload-induced
      cardiac hypertrophy, fibrosis and inflammation, whereas knocking out nNOS
      abolished these cardioprotective effects of aucubin. Blocking or knocking down
      the beta3 -adrenoceptor abolished the protective effects of aucubin in vitro.
      Furthermore, aucubin enhanced the protective effects of a beta3 -adrenoceptor
      agonist in vitro by increasing cellular cAMP levels, whereas treatment with an
      adenylate cyclase (AC) inhibitor abolished the cardioprotective effects of
      aucubin. CONCLUSIONS AND IMPLICATIONS: Aucubin suppresses oxidative stress during
      cardiac remodelling by increasing the expression of nNOS in a process that
      requires activation of the beta3 -adrenoceptor/AC/cAMP pathway. These findings
      suggest that aucubin could have potential as a treatment for cardiac remodelling
      and heart failure.

PMID- 29447433
TI  - A Step into the Future: Applications of Nanoparticle Enzyme Mimics.
AB  - We describe elementary concepts, up-to-date developments, and perspectives of the
      emerging field of nanoparticle enzyme mimics (so-called "nanozymes") at the
      interface of chemistry, biology, materials, and nanotechnology. The design and
      synthesis of functional enzyme mimics is a long-standing goal of biomimetic
      chemistry. Metal complexes, polymers and engineered biomolecules capturing the
      structure of natural enzymes or their active centers have been made to achieve
      high rates and enhanced selectivities. Still, the design of new "artificial
      enzymes" that are not related to proteins but with capacity of production and
      stability at industrial level, remains a goal. Inorganic nanoparticles bear this
      potential. Although it seems counterintuitive to compare nanoparticles and
      natural enzymes because they appear very different they share many common
      features: nano-size, irregular shape, and rich surface chemistry. These features
      enable nanomaterials to mimic reactions of natural enzymes. Representative
      examples with biomedical and environmental applications are given.

PMID- 29447435
TI  - Asymmetric dimethylarginine levels are associated with augmentation index across
      naive untreated patients with different hypertension phenotypes.
AB  - Asymmetric dimethylarginine (ADMA) is a robust marker of endothelial dysfunction
      in patients with essential hypertension. We investigated ADMA levels and their
      association with vascular damage in untreated hypertension. We enrolled
      consecutive patients with untreated, recently diagnosed hypertension and age
      matched normotensive individuals. 24-hour blood pressure, central hemodynamics,
      and arterial stiffness were recorded. A total of 311 individuals were studied:
      165 with essential hypertension, 50 with masked hypertension, 25 with white-coat
      hypertension, and 71 normotensive individuals. ADMA levels significantly
      correlated with aortic augmentation index (AIx75) (r = .156, P = .006), aortic
      pulse pressure (r = .153, P = .007) and marginally with carotid-femoral pulse
      wave velocity (r = .110, P = .051), as well as with diastolic office BP. In the
      multivariate model, aortic AIx75 and age were the only statistically significant
      predictors of ADMA. This is the largest study to document an independent
      association between ADMA and aortic AIx75 but not with other indices of arterial
      stiffness.

PMID- 29447434
TI  - Alterations in melatonin and 5-HT signalling in the colonic mucosa of mice with
      dextran-sodium sulfate-induced colitis.
AB  - BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is characterized by
      pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in
      mucosal 5-HT (serotonin) signalling occur in animal models of colitis and in
      humans suffering from IBD. Melatonin is co-released with 5-HT from the mucosa and
      has a wide variety of actions in the GI tract. Here, we examined how melatonin
      signalling is affected by colitis and determined how this relates to 5-HT
      signalling. EXPERIMENTAL APPROACH: Using electroanalytical approaches, we
      investigated how 5-HT release, reuptake and availability as well as melatonin
      availability are altered in dextran sodium sulfate (DSS)-induced colitis in mice.
      Studies were conducted to explore if melatonin treatment during active colitis
      could reduce the severity of colitis. KEY RESULTS: We observed an increase in 5
      HT and a decrease in melatonin availability in DSS-induced colitis. A significant
      reduction in 5-HT reuptake was observed in DSS-induced colitis animals. A
      reduction in the content of 5-HT was observed, but no difference in tryptophan
      levels were observed. A reduction in deoxycholic acid-stimulated 5-HT
      availability and a significant reduction in mechanically-stimulated 5-HT and
      melatonin availability were observed in DSS-induced colitis. Orally or rectally
      administered melatonin once colitis was established did not significantly
      suppress inflammation. CONCLUSION AND IMPLICATIONS: Our data suggest that DSS
      induced colitis results in a reduction in melatonin availability and an increase
      in 5-HT availability, due to a reduction/loss of tryptophan hydroxylase 1 enzyme,
      5-HT content and 5-HT transporters. Mechanosensory release was more susceptible
      to inflammation when compared with chemosensory release.

PMID- 29447436
TI  - Synthesis of a Helical Bilayer Nanographene.
AB  - A rigid, inherently chiral bilayer nanographene has been synthesized as both the
      racemate and enantioenriched M isomer (with 93 % ee) in three steps from
      established helicenes. This folded nanographene is composed of two hexa-peri
      hexabenzocoronene layers fused to a [10]helicene, with an interlayer distance of
      3.6 A as determined by X-ray crystallography. The rigidity of the helicene linker
      forces the layers to adopt a nearly aligned AA-stacked conformation, rarely
      observed in few-layer graphene. By combining the advantages of nanographenes and
      helicenes, we have constructed a bilayer system of 30 fused benzene rings that is
      also chiral, rigid, and remains soluble in common organic solvents. We present
      this as a molecular model system of bilayer graphene, with properties of interest
      in a variety of potential applications.

PMID- 29447437
TI  - J-Shaped Association Between Postoperative Levothyroxine Dosage and Fracture Risk
      in Thyroid Cancer Patients: A Retrospective Cohort Study.
AB  - Long-term administration of supraphysiologic dosages of levothyroxine can have
      detrimental effect on the bone. We aimed to investigate fracture incidence among
      post-thyroidectomy thyroid cancer patients compared with a matched comparison
      group, and explore the association between levothyroxine dosage and fracture
      risk. From the Korean National Health Insurance database, virtually all thyroid
      cancer patients who received thyroidectomy in Korea from January 1, 2004 to
      December 31, 2012 were included. Matched subjects were selected by 1:1 propensity
      score matching. Cox proportional hazards regression analysis was used to
      determine relative risk of osteoporotic fracture. Of 185,956 thyroid cancer
      patients identified, fracture events were observed in 1096 subjects (0.56%) over
      a mean 4.35 years of follow-up. Compared to the matched comparison group, thyroid
      cancer patients had no elevated risk of osteoporotic fracture (hazard ratio [HR]
      1.03; 95% confidence interval [CI], 0.94 to 1.12); however, the highest dosage
      group (>=170 MUg/day) showed significantly higher risk (HR 1.25; 95% CI, 1.07 to
      1.45), while the second quartile dosage group (115-144 MUg/day) showed lower risk
      (HR 0.71; 95% CI, 0.59 to 0.84) compared to a matched comparison group. When the
      second quartile dosage group was considered as reference, increased fracture risk
      was observed in those who took either lower (first quartile: adjusted HR 1.31;
      95% CI, 1.08 to 1.59) or higher dosage of levothyroxine (third quartile: adjusted
      HR 1.50; 95% CI, 1.26 to 1.79; fourth quartile: adjusted HR 1.79; 95% CI, 1.51 to
      2.13). Thyroid cancer patients were more likely to be treated with osteoporosis
      medication (HR 1.22; 95% CI, 1.18 to 1.26) than the matched comparison group.
      Both high and low dosage of levothyroxine treatment was associated with a higher
      risk for fractures in a J-shaped dose-dependent manner in post-thyroidectomy
      patients. Future studies are needed to determine how to optimize thyroid
      stimulating hormone (TSH) suppression and how to screen and manage fracture risk.
      (c) 2018 American Society for Bone and Mineral Research.

PMID- 29447438
TI  - Serum uric acid is associated with incidence of heart failure with preserved
      ejection fraction and cardiovascular events in patients with arterial
      hypertension.
AB  - The objective of the present study was to evaluate clinical implications of serum
      uric acid (UA) on the progression of heart failure with preserved ejection
      fraction (HFpEF) in hypertensive patients. A total of 1009 adult patients with
      left ventricular hypertrophy and suspected left ventricular diastolic dysfunction
      were enrolled at our hospital from January 2008 to December 2011. With a median
      follow-up of 7.2 years, 136 (13.2%) patients developed new-onset HFpEF and 151
      (15.0%) had major adverse cardiovascular events (MACEs). Compared with the lowest
      UA tertile of UA (<302 MUmol L-1 ), subjects in the highest tertile (>367 MUmol L
      1 ) had a higher risk of developing new-onset HFpEF (HR: 1.761, 95% CI: 1.119
      2.772, P = .015) as well as MACEs (HR: 1.664, 95% CI: 1.086-2.547, P = .019). Our
      findings indicate that hyperuricemia is associated with detrimental effects in
      terms of the incidence of new-onset HFpEF as well as MACEs in hypertensive
      patient.

PMID- 29447439
TI  - Threshold value of home pulse pressure predicting arterial stiffness in patients
      with type 2 diabetes: KAMOGAWA-HBP study.
AB  - This cross-sectional multicenter study was designed to evaluate the threshold
      value of home pulse pressure (PP) and home systolic blood pressure (SBP)
      predicting the arterial stiffness in 876 patients with type 2 diabetes. We
      measured the area under the receiver-operating characteristic curve (AUC) and
      estimated the ability of home PP to identify arterial stiffness using Youden
      Index defined cut-off point. The arterial stiffness was measured using the
      brachial-ankle pulse wave velocity (baPWV). AUC for arterial stiffness in morning
      PP was significantly greater than that in morning SBP (P < .001). AUC for
      arterial stiffness in evening PP was also significantly greater than that in
      evening SBP (P < .001). The optimal cut-off points for morning PP and evening PP,
      which predicted arterial stiffness, were 54.6 and 56.9 mm Hg, respectively. Our
      findings indicate that we should pay more attention to increased home PP in
      patients with type 2 diabetes.

PMID- 29447440
TI  - Stroke volume and proteinuria in obesity-related glomerulopathy: potential role
      in pathogenesis and choice of antihypertensive regimen.

PMID- 29447441
TI  - Design factors of femur fracture fixation plates made of shape memory alloy based
      on the Taguchi method by finite element analysis.
AB  - This study proposed a way to design femur fracture fixation plates made of shape
      memory alloy based on computed tomography (CT) images of Korean cadaveric femurs.
      To this end, 3 major design factors of femur fracture fixation plates
      (circumference angle, thickness, and inner diameter) were selected based on the
      contact pressure when a femur fracture fixation plate was applied to a cylinder
      model using the Taguchi method. Then, the effects of the design factors were
      analyzed. It was shown that the design factors were statistically significant at
      a level of p = 0.05 concerning the inner diameter and the thickness. The factors
      affecting the contact pressure were inner diameter, thickness, and circumference
      angle, in that order. Particularly, in the condition of Case 9 (inner diameter 27
      mm, thickness 2.4 mm, and circumference angle 270 degrees ), the max. average
      contact pressure was 21.721 MPa, while the min. average contact pressure was
      3.118 MPa in Case 10 (inner diameter 29 mm, thickness 2.0 mm, and circumference
      angle 210 degrees ). When the femur fracture fixation plate was applied to the
      cylinder model, the displacement due to external sliding and pulling forces was
      analyzed. As a result, the displacement in the sliding condition was at max. 3.75
      times greater than that in the pulling condition, which indicated that the
      cohesion strength between the femur fracture fixation plate and the cylinder
      model was likely to be greater in the pulling condition. When a human femur model
      was applied, the max. average contact pressure was 10.76 MPa, which was lower
      than the yield strength of a human femur (108 MPa). In addition, the analysis of
      the rib behaviors of the femur fracture fixation plate in relation to the
      recovery effect of the shape memory alloy showed that the rib behaviors varied
      depending on the arbitrarily curved shapes of the femur sections.

PMID- 29447442
TI  - Phenolic Group of alpha-Tocopherol Anchors at the Lipid-Water Interface of Fully
      Saturated Membranes.
AB  - alpha-Tocopherol is considered to carry on a very important role as an
      antioxidant for membranes and lipoproteins and other biological roles as membrane
      stabilizers and bioactive lipids. Given its essential role, it is very important
      to fully understand its location in the membrane. In this work, the vertical
      location of vitamin E in saturated membranes has been studied using biophysical
      techniques. Small- and wide-angle X-ray diffraction experiments show that alpha
      tocopherol alters the water layer between bilayers in both 1,2-dimyristoyl- sn
      glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl- sn-glycero-3-phosphocholine
      (DPPC), indicating its proximity to this surface. The quenching of the intrinsic
      fluorescence of alpha-tocopherol indicates a low quenching efficiency by
      acrylamide and a higher quenching by 5-doxyl-PC than by 9- and 16-doxyl-PC. These
      results suggest that in both DMPC and DPPC membranes, the chromanol ring is not
      far away from the surface of the membrane but within the bilayer. 1H nuclear
      Overhauser enhancement spectroscopy magic-angle spinning-nuclear magnetic
      resonance studies showed that alpha-tocopherol is localized in a similar manner
      in DMPC and DPPC membranes, with the chromanol ring embedded in the upper part of
      the hydrophobic bilayer. Using attenuated total reflection-Fourier transform
      infrared spectroscopy, it was observed that the tail chain of alpha-tocopherol
      lies nearly parallel to the acyl chains of DMPC and DPPC. Taking these results
      together, it was concluded that in both DMPC and DPPC, the hydroxyl group of the
      chromanol ring will establish hydrogen bonding with water on the membrane
      surface, and the main axis of the alpha-tocopherol molecule will be perpendicular
      to the bilayer plane.

PMID- 29447443
TI  - Inhibitor Bound Dengue NS2B-NS3pro Reveals Multiple Dynamic Binding Modes.
AB  - Dengue virus poses a significant global health threat as the source of
      increasingly deleterious dengue fever, dengue hemorrhagic fever, and dengue shock
      syndrome. As no specific antiviral treatment exists for dengue infection,
      considerable effort is being applied to discover therapies and drugs for
      maintenance and prevention of these afflictions. The virus is primarily
      transmitted by mosquitoes, and infection occurs following viral endocytosis by
      host cells. Upon entering the cell, viral RNA is translated into a large
      multisubunit polyprotein which is post-translationally cleaved into mature,
      structural and nonstructural (NS) proteins. The viral genome encodes the enzyme
      to carry out cleavage of the large polyprotein, specifically the NS2B-NS3pro
      cofactor-protease complex-a target of high interest for drug design. One class of
      recently discovered NS2B-NS3pro inhibitors is the substrate-based trifluoromethyl
      ketone containing peptides. These compounds interact covalently with the active
      site Ser135 via a hemiketal adduct. A detailed picture of the intermolecular
      protease/inhibitor interactions of the hemiketal adduct is crucial for rational
      drug design. We demonstrate, through the use of protein- and ligand-detected
      solution-state 19F and 1H NMR methods, an unanticipated multibinding mode
      behavior of a representative of this class of inhibitors to dengue NS2B-NS3pro.
      Our results illustrate the highly dynamic nature of both the covalently bound
      ligand and protease protein structure, and the need to consider these dynamics
      when designing future inhibitors in this class.

PMID- 29447444
TI  - Methodology for the Preparation and Validation of Plutonium Age Dating Materials.
AB  - The present work describes a method for the preparation and validation of
      plutonium age dating reference materials. The test samples prepared in this
      context could be used to validate experimental protocols for determining the
      production date of plutonium via the 234U/238Pu, 235U/239Pu, 236U/240Pu, and
      241Am/241Pu chronometers. The starting material was prepared using reactor-grade
      plutonium, which was purified using a dedicated method to guarantee high Pu
      recovery, while maximizing U and Am separation efficiencies. The U and Am
      separation factors were determined by the addition of high-amounts of 233U and
      243Am spikes and their remeasurement in the final product. The prepared material
      is intended for quality control and assessment of method performance in nuclear
      forensics and safeguards.

PMID- 29447445
TI  - Electronic Exchange and Correlation in van der Waals Systems: Balancing Semilocal
      and Nonlocal Energy Contributions.
AB  - Short-range correlations in motion of electrons in matter are captured well by
      semilocal exchange-correlation (XC) functionals in density functional theory
      (DFT), but long-range correlations are neglected in such models and must be
      treated by van der Waals (vdW) dispersion methods. Whereas the effective range of
      distances at which fluctuations are correlated is usually explicit in the vdW
      models, the complementary range of semilocal functionals can be observed only
      implicitly, requiring an introduction of empirical damping functions to couple
      the semilocal and nonlocal contributions to the XC energy. We present a
      comprehensive study of the interplay between these short-range and long-range
      energy contributions in eight semilocal functionals (LDA, PBE, TPSS, SCAN, PBE0,
      B3LYP, SCAN0, M06-L) and three vdW models (MBD, D3, VV10) on noncovalently bonded
      organic dimers (S66*8), molecular crystals (X23), and supramolecular complexes
      (S12L), as well as on a series of graphene-flake dimers, covering a range of
      intermolecular distances and binding energies (0.5-130 kcal/mol). The binding
      energy profiles of many of the DFT+vdW combinations differ both quantitatively
      and qualitatively, and some of the qualitative differences are independent of the
      choice of the vdW model, establishing them as intrinsic properties of the
      respective semilocal functionals. We find that while the SCAN+vdW method yields a
      narrow range of binding-energy errors, the effective range of SCAN depends on
      system size, and we link this behavior to the specific dependence of SCAN on the
      electron localization function alpha around alpha = 1. Our study provides a
      systematic procedure to evaluate the consistency of semilocal XC functionals when
      paired with nonlocal vdW models and leads us to conclude that nonempirical
      generalized-gradient and hybrid functionals are currently among the most balanced
      semilocal choices for vdW systems.

PMID- 29447446
TI  - Online Proteolysis and Glycopeptide Enrichment with Thermoresponsive Porous
      Polymer Membrane Reactors for Nanoflow Liquid Chromatography-Tandem Mass
      Spectrometry.
AB  - In this Article, we have reported a fully automated online method to carry out
      proteolysis and glycopeptide enrichment in sequence for nanoflow liquid
      chromatography-tandem mass spectrometry (nLC-ESI-MS/MS) analysis. By implementing
      two serial thermoresponsive porous polymer membrane reactors (TPPMRs), in which
      the TPPM could be immobilized either with trypsin for proteolysis or with lectins
      for glycopeptide enrichment, the entire pretreatment procedure can be performed
      online in about an hour. The TPPM was fabricated by coating polystyrene-maleic
      anhydride- N-isopropylacrylamide (PS-MAn-PNIPAm), which was synthesized by
      reversible addition-fragmentation chain transfer polymerization, on a Nylon
      sheet. Because of the thermoresponsive nature of PNIPAm, it formed micelle
      cavities and changed its morphology at elevated temperatures, resulting in
      enhanced interactions between the enzyme or lectins and the proteins/peptides
      flowing through the membrane. The performances of the TPPMs were evaluated by
      varying the temperature conditions and the amount of standard proteins, showing
      that both proteolysis and glycopeptide enrichment with online deglycosylation
      were highly efficient at 37  degrees C. The developed online serial TPPMRs-nLC
      ESI-MS/MS method was applied to the human plasma sample (1.5 MUL) and a total of
      262 N-glycopeptides could be identified from 155 glycoproteins. Thus, the present
      work demonstrates a fully automated high speed analytical protocol for online
      proteolysis and glycopeptide enrichment, which is extremely useful for analyzing
      small amounts of the proteome samples.

PMID- 29447447
TI  - DL_MG: A Parallel Multigrid Poisson and Poisson-Boltzmann Solver for Electronic
      Structure Calculations in Vacuum and Solution.
AB  - The solution of the Poisson equation is a crucial step in electronic structure
      calculations, yielding the electrostatic potential-a key component of the quantum
      mechanical Hamiltonian. In recent decades, theoretical advances and increases in
      computer performance have made it possible to simulate the electronic structure
      of extended systems in complex environments. This requires the solution of more
      complicated variants of the Poisson equation, featuring nonhomogeneous dielectric
      permittivities, ionic concentrations with nonlinear dependencies, and diverse
      boundary conditions. The analytic solutions generally used to solve the Poisson
      equation in vacuum (or with homogeneous permittivity) are not applicable in these
      circumstances, and numerical methods must be used. In this work, we present
      DL_MG, a flexible, scalable, and accurate solver library, developed specifically
      to tackle the challenges of solving the Poisson equation in modern large-scale
      electronic structure calculations on parallel computers. Our solver is based on
      the multigrid approach and uses an iterative high-order defect correction method
      to improve the accuracy of solutions. Using two chemically relevant model
      systems, we tested the accuracy and computational performance of DL_MG when
      solving the generalized Poisson and Poisson-Boltzmann equations, demonstrating
      excellent agreement with analytic solutions and efficient scaling to ~109
      unknowns and 100s of CPU cores. We also applied DL_MG in actual large-scale
      electronic structure calculations, using the ONETEP linear-scaling electronic
      structure package to study a 2615 atom protein-ligand complex with routinely
      available computational resources. In these calculations, the overall execution
      time with DL_MG was not significantly greater than the time required for
      calculations using a conventional FFT-based solver.

PMID- 29447448
TI  - Gendered racism and the sexual and reproductive health of Black and Latina Women.
AB  - OBJECTIVE: To understand health disparities, it is important to use an
      intersectional framework that examines unique experiences of oppression faced by
      particular groups due to their intersecting identities and social positions
      linked to societal structures. We focus on Black and Latina women and their
      experiences with 'gendered racism' - unique forms of oppression due to the
      intersection of race/ethnicity and gender - to foster understanding of
      disparities between Black and Latina versus White women in sexual and
      reproductive health outcomes in the U.S. Specifically, we focus on stereotype
      related gendered racism (ongoing discrimination and stereotype threat based on
      historically-rooted stereotypes about Black and Latina women's sexuality and
      motherhood) and birth control-related mistrust (ongoing mistrust of the
      government and medical system related to birth control due to historical and
      current abuses). DESIGN: We analyzed data from two survey studies with adult
      women in New York (Study 1: paper-and-pencil community data collection, N = 135,
      Mage = 43.35) and across the U.S. (Study 2: online data collection, N = 343, Mage
      = 29.49) who were currently pregnant or had at least one child and identified as
      Black, Latina, or White. RESULTS: Black and Latina women reported greater
      frequency of and concern over stereotype-related gendered racism (F(3,131) =
      17.90, p < .001 Study 1; F(3,339) = 22.23, p < .001 Study 2) and greater birth
      control-related mistrust (F(3,131) = 7.55, p < .001 Study 1; F(3,339) = 17.32, p
      < .001 Study 2) than White women did. In turn, stereotype-related gendered racism
      was positively associated with pregnancy-specific stress (beta = .40, p < .001
      Study 1; beta = .33, p < .001 Study 2), and birth control-related mistrust was
      negatively associated with sexual relationship power (beta = -.19, p = .002 Study
      2), which are factors known to contribute to birth outcomes and sexual risk,
      respectively. CONCLUSION: Findings suggest that gendered racism may play an
      important role in existing racial/ethnic disparities in women's sexual and
      reproductive health outcomes, and interventions addressing gendered racism at
      multiple levels are needed to promote health equity.

PMID- 29447449
TI  - Prognostic and Pathogenic Role of Angiopoietin-1 and -2 in Pneumonia.
AB  - RATIONALE: During pneumonia, pathogen-host interaction evokes inflammation and
      lung barrier dysfunction. Tie2 activation by angiopoietin-1 reduces, whereas Tie2
      blockade by angiopoietin-2 increases, inflammation and permeability during
      sepsis. The role of angiopoietin-1/-2 in pneumonia remains unidentified.
      OBJECTIVES: To investigate the prognostic and pathogenic impact of angiopoietins
      in regulating pulmonary vascular barrier function and inflammation in bacterial
      pneumonia. METHODS: Serum angiopoietin levels were quantified in pneumonia
      patients of two independent cohorts (n = 148, n = 395). Human postmortem lung
      tissue, pneumolysin- or angiopoietin-2-stimulated endothelial cells, isolated
      perfused and ventilated mouse lungs, and mice with pneumococcal pneumonia were
      investigated. MEASUREMENTS AND MAIN RESULTS: In patients with pneumonia,
      decreased serum angiopoietin-1 and increased angiopoietin-2 levels were observed
      as compared with healthy subjects. Higher angiopoietin-2 serum levels were found
      in patients with community-acquired pneumonia who died within 28 days of
      diagnosis compared with survivors. Receiver operating characteristic analysis
      revealed improved prognostic accuracy of CURB-65 for 28-day survival, intensive
      care treatment, and length of hospital stay if combined with angiopoietin-2 serum
      levels. In vitro, pneumolysin enhanced endothelial angiopoietin-2 release,
      angiopoietin-2 increased endothelial permeability, and angiopoietin-1 reduced
      pneumolysin-evoked endothelial permeability. Ventilated and perfused lungs of
      mice with angiopoietin-2 knockdown showed reduced permeability on pneumolysin
      stimulation. Increased pulmonary angiopoietin-2 and reduced angiopoietin-1 mRNA
      expression were observed in Streptococcus pneumoniae-infected mice. Finally,
      angiopoietin-1 therapy reduced inflammation and permeability in murine pneumonia.
      CONCLUSIONS: These data suggest a central role of angiopoietin-1/-2 in pneumonia
      evoked inflammation and permeability. Increased angiopoietin-2 serum levels
      predicted mortality and length of hospital stay, and angiopoietin-1 may provide a
      therapeutic target for severe pneumonia.

PMID- 29447453
TI  - In silico genome-wide identification and characterization of the glutathione S
      transferase gene family in Vigna radiata.
AB  - Plant glutathione S-transferases (GSTs) are integral to normal plant metabolism
      and biotic and abiotic stress tolerance. The GST gene family has been
      characterized in diverse plant species using molecular biology and bioinformatics
      approaches. In the current study, in silico analysis identified 44 GSTs in Vigna
      radiata. Of the total 44 GSTs identified, chromosomal locations of 31 GSTs were
      confirmed. The pI value of GST proteins ranged from 5.10 to 9.40. The predicted
      molecular weights ranged from 13.12 to 50 kDa. Subcellular localization analysis
      revealed that all GSTs were predominantly localized in the cytoplasm. The active
      site amino acids were confirmed to be serine in tau, phi, theta, zeta, and TCHQD;
      cysteine in lambda, DHAR, and omega; and tyrosine in EF1G. The gene architecture
      conformed to the two-exon/one-intron and three-exon/two-intron organization in
      the case of tau and phi classes, respectively. MEME analysis identified 10
      significantly conserved motifs with the width of 8-50 amino acids. The motifs
      identified were either specific to a specific GST class or were shared by
      multiple GST classes. The results of the current study will be of potential
      importance in the characterization of the GST gene family in V. radiata, an
      economically important leguminous crop.

PMID- 29447458
TI  - E-Cadherin Loss Accelerates Tumor Progression and Metastasis in a Mouse Model of
      Lung Adenocarcinoma.
AB  - Metastatic disease is the primary cause of death of patients with lung cancer,
      but the mouse models of lung adenocarcinoma do not accurately recapitulate the
      tumor microenvironment or metastatic disease observed in patients. In this study,
      we conditionally deleted E-cadherin in an autochthonous lung adenocarcinoma mouse
      model driven by activated oncogenic Kras and p53 loss. Loss of E-cadherin
      significantly accelerated lung adenocarcinoma progression and decreased survival
      of the mice. Kras;p53;E-cadherin mice had a 41% lung tumor burden, invasive grade
      4 tumors, and a desmoplastic stroma just 8 weeks after tumor initiation. One
      hundred percent of the mice developed local metastases to the lymph nodes or
      chest wall, and 38% developed distant metastases to the liver or kidney. Lung
      adenocarcinoma cancer cell lines derived from these tumors also had high
      migratory rates. These studies demonstrate that the Kras;p53;E-cadherin mouse
      model better emulates the tumor microenvironment and metastases observed in
      patients with lung adenocarcinoma than previous models and may therefore be
      useful for studying metastasis and testing new lung cancer treatments in vivo.

PMID- 29447460
TI  - The curvilinear relationship of early-life adversity and successful aging: the
      mediating role of mental health.
AB  - OBJECTIVES: The steeling effect suggests that early-life adversity can have a
      beneficial impact later in life. However, little is known about its underlying
      mechanisms and long-term outcomes . The study aimed to examine the role of early
      life adversity (ELA) on successful aging, and whether this relationship can be
      explained by mental and physical health. METHOD: Socio-demographics, early-life
      adversity (ELA), individual quality of life (iQoL), and mental and physical
      health of 270 individuals (Mage = 66.82 years, 71.5% female) were assessed.
      Polynomial regressions and mediation analyses were conducted. RESULTS:
      Significant inverse U-shaped associations were found between ELA and iQoL (beta =
      -.59, p = .005) and between ELA and mental health (beta = -.64, p = .002), but
      not between ELA and physical health. Furthermore, mental health significantly
      mediated the relationship between ELA and iQoL (b = -.84, BCa CI [-1.66, -.27]).
      CONCLUSION: Highest level of individual quality of life (i.e. successful aging)
      was related to a moderate amount of ELA. Additionally, mental health
      significantly mediated this relationship. These findings suggest that some amount
      of ELA could be beneficial for successful aging. Resource-focused interventions
      are needed to improve health and promote successful aging for an underdetected,
      at-risk subgroup with low early-life adversity.

PMID- 29447462
TI  - Exploring talk about sexuality and living gay social lives among Chinese and
      South Asian gay and bisexual men in Auckland, New Zealand.
AB  - OBJECTIVE: To identify ways Chinese and South Asian gay and bisexual men living
      in Auckland talk about issues related to sexuality and experiences of living 'gay
      social lives.' Results will be available to inform health policy and practice.
      DESIGN: A qualitative design with individual interviews and thematic analysis was
      used. Semi-structured digitally recorded interviews were undertaken with 27
      Chinese and 17 South Asian gay and bisexual men living in Auckland. RESULTS: Four
      themes in the data related to talk about sexuality and living gay social lives
      are reported: (a) 'Happy in my skin': Being gay is Ok! (b) 'To come out or not':
      Managing sexual identity, (c) 'Places to go, people to see': Connecting with
      others, and (d) 'What's wrong with being Asian': Tolerating discrimination.
      CONCLUSION: There are many similarities in the ways these men talked about their
      identity and sexuality that can be usefully considered by health policy makers
      and service planners. The concept of gay (and bisexual) sexuality had some
      salience for the men interviewed, despite the adoption and acknowledgement of
      same-sex identity being a relatively new phenomenon in some Asian countries. This
      supports the use of these terms in local health interventions. However, as these
      men closely managed their gay identity and typically had not disclosed their
      sexuality to others, including healthcare professionals, interventions to address
      the skills and comfort of healthcare providers in addressing sexuality in
      clinical settings appear warranted to facilitate optimal healthcare. These men
      are not well connected with others and this has implications for HIV health
      promotion that is based on creating cultural norms among networks to encourage
      safe sex. Discrimination results in many Chinese and South Asian gay and bisexual
      men disengaging from connecting with others and should be addressed.

PMID- 29447463
TI  - The Functional Correlate of the Loss of Terminal Bronchioles in Chronic
      Obstructive Pulmonary Disease.

PMID- 29447461
TI  - Genetic Ablation of p16INK4a Does Not Protect against Cellular Senescence in
      Mouse Models of Chronic Obstructive Pulmonary Disease/Emphysema.
AB  - Cigarette smoke (CS) affects DNA damage and cellular senescence signaling
      pathways in the pathogenesis of chronic obstructive pulmonary disease (COPD).
      p16INK4a (p16: a cyclin-dependent kinase inhibitor) is a key marker of cellular
      senescence, which is induced by CS in lung cells. It is thought that removal of
      p16 attenuates premature aging by removing senesced cells. However, the role of
      p16 in CS-induced stress-induced premature senescence (SIPS) and senescence
      associated secretory phenotype (SASP) during the development of COPD/emphysema is
      not known. We hypothesize that p16 regulates cellular senescence and DNA
      damage/repair molecular signaling targets during chronic CS-induced inflammation
      and airspace enlargement in mouse models of COPD. We used p16 global knockout
      (KO) and p16 lung epithelial cell-specific KO (p16CreCC10) mice to determine
      whether p16 removal in lung epithelium augments or protects against cellular
      senescence (SIPS and SASP) in chronic CS- and elastase-induced development of
      COPD/emphysema in mice. p16 KO mice exposed to chronic CS and p16 lung epithelial
      cell-specific KO mice exposed to elastase did not show attenuation of lung
      inflammation, altered lung function, or airspace enlargement. p16 KO and
      p16CreCC10 exposed to CS and elastase showed increases in lung senescence
      associated beta-galactosidase activity. Thus, removal of p16-positive cells did
      not protect against airspace enlargement and decline in lung function induced in
      COPD mouse models. Our findings suggest that p16 is not the only key player
      associated with CS-induced cellular senescence phenotypes (SIPS and SASP),
      decline in lung function, and airspace enlargement in COPD/emphysema.

PMID- 29447464
TI  - Intense pressure on the Royal Hobart Hospital after psychiatric bed cuts.

PMID- 29447469
TI  - Tricin isolated from Allium atroviolaceum potentiated the effect of docetaxel on
      PC3 cell proliferation: role of miR-21.
AB  - For more effectiveness and overcoming the drug resistance Chemotherapy agents,
      the combination treatment is raised. Flavonoids with different anti-cancer
      effects are an appropriate choice as lead compounds. Over expressed MiR-21 in
      prostate cancer is associated with metastasis and drug resistance to chemotherapy
      with Docetaxel. In this study, the anticancer effect of 4', 5, 7-Trihydroxy-3',
      5'-dimethoxyflavone (Tricin) was investigated with Docetaxel on PC3 cell line.
      Tricin was initially isolated from the Allium atroviolaceum by column
      chromatography and recrystallization method. The chemical structure of isolate
      was elucidated by spectroscopic techniques. IC50 of Tricin and Docetaxel were
      assessed 117.5 +/- 4.4 MUM and 0.1 +/- 0.02 nM by MTT assay, respectively.
      Analysis of results indicates the synergistic effect of combination therapy on
      decreased proliferation. MiR-21 in treated cells with Tricin significantly
      decreased compared to control cells. So, Tricin can be effective in the reduction
      of metastasis and drug resistance of Docetaxel.

PMID- 29447471
TI  - Anti-infection silver nanoparticle immobilized biomaterials facilitated by argon
      plasma grafting technology.
AB  - Many research groups have attained slow, persistent, continuous release of silver
      ions through careful experimental design using existing methods. Such methods
      effectively kill planktonic bacteria and therefore prevent surface adhesion of
      pathogens. However, the resultant modified coatings cannot provide long-term
      antibacterial efficacy due to sustained anti-microbial release. In this study,
      the anti-infection activity of AgNP immobilized biomaterials was evaluated,
      facilitated by argon plasma grafting technology and activated by bacterial
      colonization. The modified materials generated in this study showed excellent
      specificity and were active against both Gram-positive and Gram-negative biofilm
      forming bacteria, including methicillin-resistant Staphylococcus aureus,
      Staphylococcus epidermidis, and Escherichia coli. The anti-infection biomaterials
      developed in this study demonstrate several attractive advantages in comparison
      to traditional anti-bacterial surfaces loaded with antibiotics or other types of
      antibacterial agents and include (1) broad spectrum of activity against
      antibiotic resistant bacteria, (2) the unlikelihood of bacterial resistance, (3)
      specificity, (4) biocompatibility, and (5) stability.

PMID- 29447472
TI  - Viable Cell Culture Banking for Biodiversity Characterization and Conservation.
AB  - Because living cells can be saved for indefinite periods, unprecedented
      opportunities for characterizing, cataloging, and conserving biological diversity
      have emerged as advanced cellular and genetic technologies portend new options
      for preventing species extinction. Crucial to realizing the potential impacts of
      stem cells and assisted reproductive technologies on biodiversity conservation is
      the cryobanking of viable cell cultures from diverse species, especially those
      identified as vulnerable to extinction in the near future. The advent of in vitro
      cell culture and cryobanking is reviewed here in the context of biodiversity
      collections of viable cell cultures that represent the progress and limitations
      of current efforts. The prospects for incorporating collections of frozen viable
      cell cultures into efforts to characterize the genetic changes that have produced
      the diversity of species on Earth and contribute to new initiatives in
      conservation argue strongly for a global network of facilities for establishing
      and cryobanking collections of viable cells.

PMID- 29447473
TI  - Impact of Micronutrients on the Immune Response of Animals.
AB  - Vitamins and minerals (micronutrients) play an important role in regulating and
      shaping an immune response. Deficiencies generally result in inadequate or
      dysregulated cellular activity and cytokine expression, thereby affecting the
      immune response. Decreased levels of natural killer, granulocyte, and phagocytic
      cell activity and T and B cell proliferation and trafficking are associated with
      inadequate levels of micronutrients, as well as increased susceptibility to
      various adverse health conditions, including inflammatory disorders, infection,
      and altered vaccine efficacy. In addition, most studies of micronutrient
      modulation of immune responses have been done in rodents and humans, thus
      limiting application to the health and well-being of livestock and companion
      animals. This exploratory review elucidates the role of vitamins and minerals on
      immune function and inflammatory responses in animals (pigs, dogs, cats, horses,
      goats, sheep, and cattle), with reference to rodents and humans.

PMID- 29447474
TI  - Introduction.

PMID- 29447475
TI  - The Divergent Genomes of Teleosts.
AB  - Boasting nearly 30,000 species, teleosts account for half of all extant
      vertebrates and approximately 98% of all ray-finned fish species
      (Actinopterygii). Teleosts are also the largest and most diverse group of
      vertebrates, exhibiting an astonishing level of morphological, physiological, and
      behavioral diversity. Previous studies had indicated that the teleost lineage has
      experienced an additional whole-genome duplication event. Recent comparative
      genomic analyses of teleosts and other bony vertebrates using spotted gar (a
      nonteleost ray-finned fish) and elephant shark (a cartilaginous fish) as
      outgroups have revealed several divergent features of teleost genomes. These
      include an accelerated evolutionary rate of protein-coding and nucleotide
      sequences, a higher rate of intron turnover, loss of many potential cis
      regulatory elements and shorter conserved syntenic blocks. A combination of these
      divergent genomic features might have contributed to the evolution of the amazing
      phenotypic diversity and morphological innovations of teleosts.

PMID- 29447477
TI  - Inhibition of the lethality of Shiga-like toxin-1 by functional gold
      nanoparticles.
AB  - Escherichia coli O157:H7 is a pathogen, which can generate Shiga-like toxins
      (SLTs) and cause hemolytic-uremic syndrome. Foodborne illness outbreaks caused by
      E. coli O157:H7 have become a global issue. Since SLTs are quite toxic, effective
      medicines that can reduce the damage caused by SLTs should be explored. SLTs
      consist of a single A and five B subunits, which can inhibit ribosome activity
      for protein synthesis and bind with the cell membrane of host cells,
      respectively. Pigeon ovalbumin (POA), i.e. a glycoprotein, is abundant in pigeon
      egg white (PEW) proteins. The structure of POA contains Gal-alpha(1->4)-Gal
      beta(1->4)-GlcNAc ligands, which have binding affinity toward the B subunit in
      SLT type-1 (SLT-1B). POA immobilized gold nanoparticles (POA-Au NPs) can be
      generated by reacting PEW proteins with aqueous tetrachloroauric acid in one-pot.
      The generated POA-Au NPs have been demonstrated to have selective trapping
      capacity toward SLT-1B previously. Herein, we explore that POA-Au NPs can be used
      as protective agents to neutralize the toxicity of SLT-1 in SLT-1-infected model
      cells. The results show that the cells can be completely rescued when a
      sufficient amount of POA-Au NPs is used to treat the SLT-1-infected cells within
      1 h.

PMID- 29447476
TI  - Sequencing and characterization of lncRNAs in the breast muscle of Gushi and
      Arbor Acres chickens.
AB  - Chicken muscle quality is one of the most important factors determining the
      economic value of poultry, and muscle development and growth are affected by
      genetics, environment, and nutrition. However, little is known about the
      molecular regulatory mechanisms of long non-coding RNAs (lncRNAs) in chicken
      skeletal muscle development. Our study aimed to better understand muscle
      development in chickens and thereby improve meat quality. In this study, Ribo
      Zero RNA-Seq was used to investigate differences in the expression profiles of
      muscle development related genes and associated pathways between Gushi (GS) and
      Arbor Acres (AA) chickens. We identified two muscle tissue specific expression
      lncRNAs. In addition, the target genes of these lncRNAs were significantly
      enriched in certain biological processes and molecular functions, as demonstrated
      by Gene Ontology (GO) analysis, and these target genes participate in five
      signaling pathway, as revealed by an analysis of the Kyoto Encyclopedia of Genes
      and Genomes (KEGG) database. Taken together, these data suggest that different
      lncRNAs might be involved in regulating chicken muscle development and growth and
      provide new insight into the molecular mechanisms of lncRNAs.

PMID- 29447478
TI  - Dendritic platforms for biomimicry and biotechnological applications.
AB  - Dendrimers, commonly referred to as polymeric trees, offer endless opportunities
      for biotechnological and biomedical applications. By controlling the type,
      length, and molecular weight of the core, branches and end groups, respectively,
      the chemical functionality and topology of dendrimeric archetypes can be
      customized which further can be applied to achieve required solubility,
      biodegradability, diagnosis and other applications. Given the physicochemical
      variability of the dendrimers and their hybrids, this review attempts to discuss
      a full spectrum of recent advances and strides made by these "perfectly designed
      structures". An extensive biotech/biomimicry application profiling of dendrimers
      is provided with focus on complex archetypical designs such as protein biomimicry
      (angiogenic inhibitors, regenerative hydroxyapatite and collagen) and
      biotechnology applications. In terms of biotechnological advances, dendrimers
      have provided distinctive advantages in the fields of biocatalysis, microbicides,
      artificial lights, mitochondrial function modulation, vaccines, tissue
      regeneration and repair, antigen carriers and even biosensors. In addition, this
      review provides overview of the extensive chemo-functionalization opportunities
      available with dendrimers which makes them a perfect candidate for forming drug
      conjugates, protein hybrids, bio mimics, lipidic derivatives, metal deposits and
      nanoconjugates thereby making them the most multifunctional platforms for diverse
      biotechnological applications.

PMID- 29447479
TI  - Two new lignans from Horsfieldia kingii.
AB  - Two new dibenzylbutyrolactol lignans and three known dibenzylbutyrolactone
      lignans were isolated from the twigs and leaves of Horsfieldia kingii. Their
      structures were elucidated by spectroscopic analysis. Cytotoxicity evaluation of
      these compounds against five human tumour lines showed no inhibitory effects.

PMID- 29447480
TI  - Intramuscular Distribution of the Abducens Nerve in the Lateral Rectus Muscle for
      the Management of Strabismus.
AB  - AIMS: To elucidate the intramuscular distribution and branching patterns of the
      abducens nerve in the lateral rectus (LR) muscle so as to provide anatomical
      confirmation of the presence of compartmentalization, including for use in
      clinical applications such as botulinum toxin injections. METHODS: Thirty whole
      mount human cadaver specimens were dissected and then Sihler's stain was applied.
      The basic dimensions of the LR and its intramuscular nerve distribution were
      investigated. The distances from the muscle insertion to the point at which the
      abducens nerve enters the LR and to the terminal nerve plexus were also measured.
      RESULTS: The LR was 46.0 mm long. The abducens nerve enters the muscle on the
      posterior one-third of the LR and then typically divides into a few branches
      (average of 1.8). This supports a segregated abducens nerve selectively
      innervating compartments of the LR. The intramuscular nerve distribution showed a
      Y-shaped ramification with root-like arborization. The intramuscular nerve course
      finished around the middle of the LR (24.8 mm posterior to the insertion point)
      to form the terminal nerve plexus. This region should be considered the optimal
      target site for botulinum toxin injections. We have also identified the presence
      of an overlapping zone and communicating nerve branches between the neighboring
      LR compartments. CONCLUSION: Sihler's staining is a useful technique for
      visualizing the entire nerve network of the LR. Improving the knowledge of the
      nerve distribution patterns is important not only for researchers but also
      clinicians to understand the functions of the LR and the diverse pathophysiology
      of strabismus.

PMID- 29447481
TI  - Regularity changes of the retinal nerve fiber layer and macular ganglion cell
      complex in patients with the amnestic mild cognitive impairment.
AB  - : Purpose/aim: We investigated the regularity changes of the retinal nerve fiber
      layer (RNFL) and macular ganglion cell complex (mGCC) of the amnestic mild
      cognitive impairment (aMCI) patients in this prospective cohort study. MATERIALS
      AND METHODS: Twenty-four aMCI patients and 30 health controls, who are more than
      60 years old, were recruited into the study. The RNFL and the mGCC average
      thickness were measured with Fourier-domain optical coherence tomography (FD
      OCT). RESULTS: Compared with that in the controls, the intraocular pressure (IOP)
      was significantly lower in the aMCI patients. A significant decrease in RNFL
      thickness in superior temporal, temporal upper (TU), and temporal upper and lower
      (TL) (TU+TL) quadrants was found in the aMCI patients than in the controls. The
      average thickness of the mGCC was also significantly thinner in the aMCI patients
      than in the controls. CONCLUSIONS: Retinal degeneration in the aMCI patients
      detected by OCT together with lower IOP may indicate disease pathological
      progression.

PMID- 29447482
TI  - Role of vitamin A supplementation in prevention of bronchopulmonary dysplasia in
      extremely low birth weight neonates: a systematic review of randomized trials.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is one of the most common
      consequence of extreme prematurity (<28 weeks of gestation). BPD affects
      approximately 55% of extremely low birth weight (ELBW) neonates. AIMS: The aim of
      this systematic review is to evaluate the role of vitamin A supplementation in
      prevention of BPD in ELBW neonates. METHOD: The literature search was done for
      various randomized control trial (RCT) by searching the Cochrane Central Register
      of Controlled Trials (CENTRAL), PubMed, EMBASE, and ongoing clinical trials.
      RESULTS: This review included two RCTs that fulfilled inclusion criteria. There
      were statistically significant reduction in the incidence of BPD (oxygen
      requirement at 36 weeks of postmenstrual age (PMA)) (relative risk (RR) 0.88;
      95%CI 0.77-0.99; p = .04; NNTB 14) and borderline significant reduction in
      combined outcomes of mortality/BPD (oxygen requirement at 36 weeks of PMA) (RR
      0.90; 95%CI 0.82-1.00; p = .05). However, oxygen requirement at 28 days of life
      and combined outcome of mortality/BPD (oxygen requirement at 28 days of life)
      were not statistically significant. CONCLUSIONS: The role of vitamin A
      supplementation in the prevention of BPD is supported by the current evidences.
      However, due to limited number of studies, current evidences are not sufficient
      which can translate into routine clinical practice. We need large high-quality
      trials, with sufficient power to reliably assess clinically relevant differences
      in outcomes.

PMID- 29447483
TI  - The art of recovery: outcomes from participatory arts activities for people using
      mental health services.
AB  - BACKGROUND: There is a growing evidence base for the use of participatory arts
      for the purposes of health promotion. In recent years, recovery approaches in
      mental healthcare have become commonplace in English speaking countries amongst
      others. There are few studies that bring together these two fields of practice.
      AIMS: The two aims of this study were (a) to investigate the validity of the
      CHIME framework for characterising the experience of Participatory Arts and (b)
      to use the CHIME framework to investigate the relationship between participatory
      arts and mental health recovery. METHOD: The study employed a two-phase
      methodology: a rapid review of relevant literature followed by secondary analysis
      of qualitative data collected from 38 people who use mental health service who
      took part in participatory arts activities designed to improve mental health.
      RESULTS: Each of the recovery processes identified by CHIME are present in the
      qualitative research literature as well as in the data of the secondary analysis.
      CONCLUSIONS: Participatory arts activities produce outcomes which support
      recovery, specifically including enhancing connectedness and improving hope. They
      can be recommended to people living with mental health problems.

PMID- 29447484
TI  - Cationic DDA/TDB liposome as a mucosal vaccine adjuvant for uptake by dendritic
      cells in vitro induces potent humoural immunity.
AB  - The cationic dimethyldioctadecylammonium/trehalose 6,6,9-dibehenate (DDA/TDB)
      liposome is as a strong adjuvant system for vaccines, with remarkable
      immunostimulatory activity. The mucosal administration of vaccines is a potential
      strategy for inducing earlier and stronger mucosal immune responses to infectious
      diseases. In this study, we assessed whether the intranasal administration of
      cationic DDA/TDB liposomes combined with influenza antigen A (H3N2) can be used
      as a highly efficacious vaccine to induce mucosal and systemic antibody
      responses. Confocal laser scanning microscopy and a flow-cytometric analysis
      showed that the uptake of the cationic DDA/TDB liposome carrier was significantly
      higher than that of neutral 1,2-distearoyl-sn-glycero-3
      phosphocholine/cholesterol (DSPC/Chol) or cationic 1,2-dioleoyl-3
      trimethylammonium-propane/3beta-(N-[N',N'-dimethylaminoethane]-carbamoyl
      (DOTAP/DC-Chol) liposomes. Our results indicate that the cationic DDA/TDB
      liposome is more effective in facilitating its uptake by dendritic cells (DCs) in
      vitro than the DSPC/Chol or DOTAP/DC-Chol liposome. DCs treated with DDA/TDB
      liposomes strongly expressed CD80, CD86, and MHC II molecules, whereas those
      treated with DSPC/Chol or DOTAP/DC-Chol liposomes did not. C57BL/6 mice
      intranasally immunized with H3N2-encapsulating cationic DDA/TDB liposomes had
      significantly higher H3N2-specific s-IgA levels in their nasal wash fluid than
      those treated with other formulations. The DDA/TDB liposomes also simultaneously
      enhanced the serum IgG IgG2a, IgG1, and IgG2b antibody responses. In summary,
      DDA/TDB liposomes effectively facilitated their uptake by DCs and DCs maturation
      in vitro, and induced significantly higher mucosal IgA, systemic IgG, IgG1, and
      IgG2b antibody titres than other formulations after their intranasal
      administration in vivo. These results indicate that DDA/TDB liposomes are a
      promising antigen delivery carrier for clinical antiviral applications.

PMID- 29447485
TI  - Should women be screened for osteoporosis at midlife?
AB  - Osteoporosis and associated fractures are common in women after midlife and will
      increase as the population ages. Osteoporosis-related fractures cause a
      significant increase in morbidity and mortality. Osteoporosis decreases the
      quality of life and productivity of many older women, with an increasing burden
      on health-care resources. Future risk of fracture can be managed by evidence
      based interventions. It is thus appropriate to estimate the future risk of
      fracture in all women at the age of 50 years or at menopause, whichever occurs
      first. This can be achieved in a non-invasive fashion by targeted clinical
      history-taking. The future risk of fracture can be quantified using computerized
      models that integrate all risk factors, with or without dual-energy X-ray
      absorptiometry (DXA). Individuals found to be at increased risk of fracture need
      also to be assessed by DXA and, in the absence of lateral vertebral assessment,
      also by conventional X-ray imaging. All women should be screened by DXA at the
      age of 65 years, if not done before that time. At the age of 50, all women should
      be informed about a bone-friendly lifestyle.

PMID- 29447486
TI  - The Development of Mid-Wavelength Photoresponsivity in the Mouse Retina.
AB  - PURPOSE: Photoreceptors in the mouse retina express much of the molecular
      machinery necessary for phototransduction and glutamatergic transmission prior to
      eye opening at postnatal day 13 (P13). Light responses have been observed
      collectively from rod and cone photoreceptors via electroretinogram recordings as
      early as P13 in mouse, and the responses are known to become more robust with
      maturation, reaching a mature state by P30. Photocurrents from single rod outer
      segments have been recorded at P12, but no earlier, and similar studies on cone
      photoreceptors have been done, but only in the adult mouse retina. In this study,
      we wanted to document the earliest time point in which outer retinal
      photoreceptors in the mouse retina begin to respond to mid-wavelength light.
      METHODS: Ex-vivo electroretinogram recordings were made from isolated mouse
      retinae at P7, P8, P9, P10, and P30 at seven different flash energies (561 nm).
      The a-wave was pharmacologically isolated and measured at each developmental time
      point across all flash energies. RESULTS: Outer-retinal photoreceptors generated
      a detectable response to mid-wavelength light as early as P8, but only at
      photopic flash energies. a-wave intensity response curves and kinetic response
      properties are similar to the mature retina as early as P10. CONCLUSION: These
      data represent the earliest recorded outer retinal light responses in the rodent.
      Photoreceptors are electrically functional and photoresponsive prior to eye
      opening, and much earlier than previously thought. Prior to eye opening, critical
      developmental processes occur that have been thought to be independent of outer
      retinal photic modulation. However, these data suggest light acting through outer
      retinal photoreceptors has the potential to shape these critical developmental
      processes.

PMID- 29447487
TI  - Perianal Crohn's disease - association with significant inflammatory activity in
      proximal small bowel segments.
AB  - OBJECTIVES: Perianal Crohn's disease (CD) prevalence varies according to the
      disease location, being particularly frequent in patients with colonic
      involvement. We aimed to evaluate small bowel involvement and compare small bowel
      capsule endoscopy findings and inflammatory activity between patients with and
      without perianal disease. MATERIALS AND METHODS: Retrospective single-center
      study including 71 patients - all patients with perianal CD (17 patients) who
      performed a small bowel capsule endoscopy were included, and non-perianal CD
      patients were randomly selected (54 patients). Clinical and analytical variables
      at diagnosis were reviewed. Statistical analysis was performed with SPSS v21.0
      and a two-tailed p value <.05 was defined as indicating statistical significance.
      RESULTS: Patients had a median age of 30 +/- 16 years with 52.1% females.
      Perianal disease was present in 23.9%. Patients with perianal disease had
      significantly more relevant findings (94.1% vs 66.6%, p = .03) and erosions
      (70.6% vs 42.6%, p = .04), however, no differences were found between the two
      groups regarding ulcer, villous edema and stenosis detection. Overall, patients
      with perianal disease had more frequently significant small bowel inflammatory
      activity, defined as a Lewis Score >=135 (94.1% vs 64.8%, p = .03), and higher
      Lewis scores in the first and second tertiles (450 +/- 1129 vs 0 +/- 169, p = .02
      and 675 +/- 1941 vs 0 +/- 478, p = .04, respectively). No differences were found
      between the two groups regarding third tertile inflammatory activity assessed
      with the Lewis Score. CONCLUSION: Patients with perianal CD have significantly
      higher inflammatory activity in the small bowel, particularly in proximal small
      bowel segments, when compared with patients without perianal disease.

PMID- 29447488
TI  - Long-term effects of Lee Silverman Voice Treatment on daily voice use in
      Parkinson's disease as measured with a portable voice accumulator.
AB  - This study examines the effects of an intensive voice treatment focusing on
      increasing voice intensity, LSVT LOUD(r) Lee Silverman Voice Treatment, on voice
      use in daily life in a participant with Parkinson's disease, using a portable
      voice accumulator, the VoxLog. A secondary aim was to compare voice use between
      the participant and a matched healthy control. Participants were an individual
      with Parkinson's disease and his healthy monozygotic twin. Voice use was
      registered with the VoxLog during 9 weeks for the individual with Parkinson's
      disease and 2 weeks for the control. This included baseline registrations for
      both participants, 4 weeks during LSVT LOUD for the individual with Parkinson's
      disease and 1 week after treatment for both participants. For the participant
      with Parkinson's disease, follow-up registrations at 3, 6, and 12 months post
      treatment were made. The individual with Parkinson's disease increased voice
      intensity during registrations in daily life with 4.1 dB post-treatment and 1.4
      dB at 1-year follow-up compared to before treatment. When monitored during
      laboratory recordings an increase of 5.6 dB was seen post-treatment and 3.8 dB at
      1-year follow-up. Changes in voice intensity were interpreted as a treatment
      effect as no significant correlations between changes in voice intensity and
      background noise were found for the individual with Parkinson's disease. The
      increase in voice intensity in a laboratory setting was comparable to findings
      previously reported following LSVT LOUD. The increase registered using ambulatory
      monitoring in daily life was lower but still reflecting a clinically relevant
      change.

PMID- 29447489
TI  - Compulsory Use of the Backboard is Associated with Increased Frequency of
      Thoracolumbar Imaging.
AB  - BACKGROUND: Backboards have been shown to cause pain in uninjured patients. This
      may alter physical exam findings, leading emergency department (ED) providers to
      suspect a spinal injury when none exists resulting in additional imaging of the
      thoracolumbar spine. New York had previously employed a "Spinal Immobilization"
      protocol that included compulsory backboard application for all patients with
      suspected spinal injuries. In 2015, New York instituted a new "Spinal Motion
      Restriction" protocol that made backboard use optional for these patients. The
      objective of this study was to determine if this protocol change was associated
      with decreased backboard utilization and ED thoracolumbar spine imaging. METHODS:
      This was a retrospective before-and-after chart review of subjects transported by
      a single emergency medical services (EMS) agency to one of four EDs for emergency
      calls dispatched as motor vehicle collisions (MVC). EMS and ED data were included
      for all calls within a 6-month interval before and after the protocol change. The
      protocol change was implemented in the second half of 2015. Subject demographics,
      backboard use, and spine imaging were reviewed for the intervals January-June
      2015 and January-June 2016. RESULTS: There were 818 subjects in the before period
      and 796 subjects in the after period. Subjects were similar in terms of gender,
      age and type of MVC in both periods. A backboard was utilized for 440 (54%)
      subjects in the before period and 92 (12%) subjects in the after period (p <
      0.001). ED thoracic spine imaging was performed on 285 (35%) subjects in the
      before period, and 235 (30%) subjects in the after period (p = 0.02). ED lumbar
      spine imaging was performed for 335 (41%) subjects in the before period, and 281
      (35%) subjects in the after period (p = 0.02). CONCLUSION: A shift from a spinal
      immobilization protocol to a spinal motion restriction protocol was associated
      with a decrease in backboard utilization by EMS providers and a decrease in
      thoracolumbar spine imaging by ED providers.

PMID- 29447490
TI  - Combined effects of artificial dermis and vascular endothelial growth factor
      concentration gradient on wound healing in diabetic porcine model.
AB  - Wounds in patients with diabetes mellitus are one of the most prevalent impaired
      wounds in the world. Vascular endothelial growth factor (VEGF) is one of the most
      important proangiogenic mediators. Artificial dermal (AD) such as Pelnac(r) has
      been shown, in humans and animal models, a great therapeutic potential in full
      thickness skin wounds. We attempt to promote the wound healing in diabetic
      porcine models through combined use of AD and constant concentration of VEGF or
      VEGF concentration gradient. We created full-thickness excisional wounds in
      diabetic animal models. Analyzed the healing process through images, histology
      and immunohistochemistry. Results show that the combination of AD and
      concentration gradient of VEGF could provide an appropriate angiogenesis, improve
      granulation formation, increase epithelization and maintain the VEGF levels of
      the wound bed. Eventually accelerate the direct healing of diabetic wounds or
      make good preparation for secondary skin graft.

PMID- 29447491
TI  - Association between Th1/Th2 immune imbalance and obesity in women with or without
      polycystic ovary syndrome.
AB  - OBJECTIVES: This study aimed to investigate the Th1/Th2 cells in peripheral blood
      of PCOS patients, and assess the potential correlation between Th1/Th2 imbalance
      and obesity. METHODS: Thirty-nine PCOS patients and 23 age-matched controls were
      enrolled. The PBMCs were obtained before pharmacological intervention in women
      with or without PCOS. The profiles of Th1 (IFN-gamma) and Th2 (IL-4) cytokines of
      CD3+CD- T lymphocyte subsets were analyzed by flow cytometry. Plasma sex hormones
      including E2, T, FSH, LH, and FINS, FPG were measured, together with BMI, WC,
      LH/FSH, E2/T and HOMA-IR index being calculated. Association between Th1/Th2
      imbalance and BMI, WC were evaluated. RESULTS: The proportion of Th1 cells and
      Th1/Th2 ratio were significantly higher in PCOS patients than those in controls,
      accompanied by elevated T, LH, LH/FSH, FINS, HOMA-IR index and reduced E2/T. The
      Th1/Th2 ratio was increased when BMI and WC were enhanced in PCOS. Moreover, the
      significant difference of Th1/Th2 ratio was observed between WC subgroups of
      PCOS. CONCLUSIONS: It is concluded that Th1 type immunity is predominant in
      systemic immunization of PCOS patients. Th1/Th2 immune imbalance is connected
      with obesity, especially abdominal obesity, and may be one of the underlying
      mechanism for the pathogenesis of PCOS.

PMID- 29447492
TI  - Physiotherapists' management of challenging situations in guiding people with
      rheumatoid arthritis to health-enhancing physical activity.
AB  - OBJECTIVES: To explore strategies used by physiotherapists (PTs) in guiding
      people with rheumatoid arthritis to health-enhancing physical activity (HEPA) in
      a group setting during a 1-year intervention study. METHODS: Exploratory design
      with qualitative video analysis performed in three steps. Eleven female PTs were
      video recorded while leading support group sessions aiming at facilitating HEPA
      (twice-weekly exercise sessions at public gyms and 150 weekly minutes of
      moderately intense aerobic physical activity). RESULTS: Three categories of
      challenging situations emerged. They occurred when the HEPA intervention
      participants reported barriers to performing physical activity, when they
      neglected to use the planning tool for physical activity as intended in the
      program, and when they received negative results from physical capacity tests.
      PTs used different strategies to manage these challenges, with main focus either
      on information-giving, corresponding to a traditional health professional
      approach, or utilizing group resources by organizing participation. CONCLUSIONS:
      This study provides detailed descriptions of PTs' clinical behavior in video
      recorded sessions. The results imply that motivated PTs can, despite their
      biomedical and practitioner-focused training, learn to adapt their communication
      strategies to different situations, altering between traditional information
      giving and utilizing group resources by organizing participation.

PMID- 29447493
TI  - Vitamin D and ferritin correlation with chronic neck pain using standard
      statistics and a novel artificial neural network prediction model.
AB  - AIM: Despite the high prevalence of chronic neck pain, there is limited consensus
      about the primary etiology, risk factors, diagnostic criteria and therapeutic
      outcome. Here, we aimed to determine if Ferritin and Vitamin D are modifiable
      risk factors with chronic neck pain using slandered statistics and artificial
      intelligence neural network (ANN). METHODS: Fifty-four patients with chronic neck
      pain treated between February 2016 and August 2016 in King Abdullah University
      Hospital and 54 patients age matched controls undergoing outpatient or minor
      procedures were enrolled. Patients and control demographic parameters, height,
      weight and single measurement of serum vitamin D, Vitamin B12, ferritin, calcium,
      phosphorus, zinc were obtained. An ANN prediction model was developed. RESULTS:
      The statistical analysis reveals that patients with chronic neck pain have
      significantly lower serum Vitamin D and Ferritin (p-value <.05). 90% of patients
      with chronic neck pain were females. Multilayer Feed Forward Neural Network with
      Back Propagation(MFFNN) prediction model were developed and designed based on
      vitamin D and ferritin as input variables and CNP as output. The ANN model output
      results show that, 92 out of 108 samples were correctly classified with 85%
      classification accuracy. CONCLUSIONS: Although Iron and vitamin D deficiency
      cannot be isolated as the sole risk factors of chronic neck pain, they should be
      considered as two modifiable risk. The high prevalence of chronic neck pain,
      hypovitaminosis D and low ferritin amongst women is of concern. Bioinformatics
      predictions with artificial neural network can be of future benefit in
      classification and prediction models for chronic neck pain. We hope this initial
      work will encourage a future larger cohort study addressing vitamin D and iron
      correction as modifiable factors and the application of artificial intelligence
      models in clinical practice.

PMID- 29447495
TI  - Erratum.

PMID- 29447494
TI  - High dose vitamin D supplementation can improve menstrual problems, dysmenorrhea,
      and premenstrual syndrome in adolescents.
AB  - Vitamin D has a crucial role in female reproduction, possibly through its effects
      on calcium homeostasis, cyclic sex steroid hormone fluctuations, or
      neurotransmitter function. We have assessed the effects of vitamin D
      supplementation on dysmenorrhea and premenstrual syndrome (PMS) in adolescents.
      In this study, 897 adolescent girls living in Mashhad and Sabzevar, Iran,
      received nine high-dose vitamin D supplements (as 50,000 IU/week of
      cholecalciferol) and were followed up over 9 weeks. We evaluated the effect of
      vitamin D supplementation on individuals in four categories: those with only PMS;
      individuals with only dysmenorrhea; subjects with both PMS and dysmenorrhea and
      normal subjects. The prevalence of PMS after the intervention fell from 14.9% to
      4.8% (p < .001). Similar results were also found for the prevalence of subjects
      with dysmenorrhea (35.9% reduced to 32.4%), and in subjects with both PMS and
      dysmenorrhea (32.7% reduced 25.7%). Vitamin D supplementation was associated with
      a reduction in the incidence of several symptoms of PMS such as backache and
      tendency to cry easily as well as decrement in pain severity of dysmenorrhea (p <
      .05). High dose vitamin D supplementation can reduce the prevalence of PMS and
      dysmenorrhea as well as has positive effects on the physical and psychological
      symptoms of PMS.

PMID- 29447496
TI  - Cancer.Net.

PMID- 29447497
TI  - Planet Cancer: A Community of Young Adults With Cancer.

PMID- 29447498
TI  - The Clinical Practice Committee: A Look Ahead.

PMID- 29447499
TI  - Concurrent Infusions.
AB  - Clarification of the appropriate use of the concurrent drug administration code.

PMID- 29447500
TI  - Financial Management in Oncology Practice, Part 2: Billing and Collections.
AB  - It pays off to learn how to code accurately and how to make sure that what you
      legitamately earned is billed correctly and collected on time.

PMID- 29447501
TI  - Principles of Safe Practice Using an Oncology EHR System for Chemotherapy
      Ordering, Preparation, and Administration, Part 1 of 2.
AB  - An outline of broad principles that should be considered when integrating an
      electronic health record, and in particular, a chemotherapy ordering module, into
      practice.

PMID- 29447502
TI  - Erratum.

PMID- 29447503
TI  - The effects of all-trans retinoic acid on estrogen receptor signaling in the
      estrogen-sensitive MCF/BUS subline.
AB  - Estrogen receptor alpha (ERalpha) and retinoic acid receptors (RARs) play
      important and opposite roles in breast cancer growth. While exposure to ERalpha
      agonists such as 17beta-estradiol (E2) is related to proliferation, RAR agonists
      such as all-trans retinoic acid (AtRA) induce anti-proliferative effects.
      Although crosstalk between these pathways has been proposed, the molecular
      mechanisms underlying this interplay are still not completely unraveled. The aim
      of this study was to evaluate the effects of AtRA on ERalpha-mediated signaling
      in the ERalpha positive cell lines MCF7/BUS and U2OS-ERalpha-Luc to investigate
      some of the possible underlying modes of action. To do so, this study assessed
      the effects of AtRA on different ERalpha-related events such as ERalpha-mediated
      cell proliferation and gene expression, ERalpha-coregulator binding and ERalpha
      subcellular localization. AtRA-mediated antagonism of E2-induced signaling was
      observed in the proliferation and gene expression studies. However, AtRA showed
      no remarkable effects on the E2-driven coregulator binding and subcellular
      distribution of ERalpha. Interestingly, in the absence of E2, ERalpha-mediated
      gene expression, ERalpha-coregulator binding and ERalpha subcellular mobilization
      were increased upon exposure to micromolar concentrations of AtRA found to
      inhibit cell proliferation after long-term exposure. Nevertheless, experiments
      using purified ERalpha showed that direct binding of AtRA to ERalpha does not
      occur. Altogether, our results using MCF7/BUS and U2OS-ERalpha-Luc cells suggest
      that AtRA, without being a direct ligand of ERalpha, can indirectly interfere on
      basal ERalpha-coregulator binding and basal ERalpha subcellular localization in
      addition to the previously described crosstalk mechanisms such as competition of
      ERs and RARs for DNA binding sites.

PMID- 29447504
TI  - Resources Available When Dealing With Commercial Payers.

PMID- 29447505
TI  - Working Smarter Toward Quality Care.

PMID- 29447506
TI  - What Our Leaders Are Reading.

PMID- 29447507
TI  - The HIPAA Security Regulations.

PMID- 29447508
TI  - Spotlight on the Association of Northern California Oncologists.

PMID- 29447509
TI  - David Brailer Aims to Bring Down Barriers to EHRs: Says Oncologists Can Help.

PMID- 29447510
TI  - PLWC Expands Psychological Content in Coping Section.

PMID- 29447511
TI  - Efficient Staffing Patterns.

PMID- 29447512
TI  - The Multiple Myeloma Research Foundation: Educating the Myeloma Community on
      Recent Treatment Innovations.

PMID- 29447513
TI  - Q&A From ASCO's Coding and Reimbursement Hotline.
AB  - This column provides oncology practitioners and their staff with important
      information about reimbursement, coding, coverage, and regulatory policies.
      Questions for future issues should be sent to practice@asco.org or by calling the
      coding and reimbursement hotline at 703-299-1050.

PMID- 29447514
TI  - The American Society of Hematology: Advancing Knowledge and Treatment of Blood
      Disorders.

PMID- 29447515
TI  - American Cancer Society.

PMID- 29447517
TI  - Q&A From ASCO's Coding and Reimbursement Hotline.

PMID- 29447516
TI  - Mind the Gap.

PMID- 29447518
TI  - Effective Volunteer Leadership: ASCO State Affiliates Share Their Stories.

PMID- 29447519
TI  - Colorectal Cancer: The Cancer Research and Prevention Foundation's Dialogue for
      Action.

PMID- 29447520
TI  - CMS Scales Back Physician Voluntary Reporting Program.

PMID- 29447522
TI  - New Look for PLWC: Site Redesign Features Even More Information for Your
      Patients.

PMID- 29447521
TI  - Pay-for-Performance Programs in the Private Sector.

PMID- 29447523
TI  - Clinical Trials Participation Awards Presented to Practices in Dallas, Cedar
      Rapids, and Miami Beach.

PMID- 29447524
TI  - Employer or Coworker: Staffing Issues for Hospital-Based Physicians.

PMID- 29447525
TI  - What to Look for in the Second Half of the 109th Congress.

PMID- 29447526
TI  - PLWC Expands Resources.

PMID- 29447527
TI  - CancerCare: Help and Hope in a Time of Crisis.

PMID- 29447528
TI  - Society of Gynecologic Oncologists.

PMID- 29447529
TI  - Erratum.

PMID- 29447530
TI  - State Society Meetings and Compliance With CME Sponsorship Rules: ASCO Can Help.

PMID- 29447531
TI  - Medical Errors: Focusing More on What and Why, Less on Who.

PMID- 29447532
TI  - Getting Involved: Advocating Locally for National Impact.

PMID- 29447533
TI  - Principles and Tactics of Negotiation.

PMID- 29447534
TI  - Skilled Nursing Facility Consolidated Billing.

PMID- 29447535
TI  - Electronic Health Records for the Practicing Oncologist: 2007 Update on ASCO's
      Role.

PMID- 29447536
TI  - Electronic Health Records: How the New Stark Law and Anti-Kickback Rules May Help
      Speed Adoption.

PMID- 29447537
TI  - Planning for Success.

PMID- 29447538
TI  - Staff Recognition and Appreciation.

PMID- 29447539
TI  - Multidisciplinary Clinics in Oncology: The Hidden Pitfalls.

PMID- 29447540
TI  - Multidisciplinary Care in the Community Setting.

PMID- 29447541
TI  - JTC-801 exerts anti-proliferative effects in human osteosarcoma cells by inducing
      apoptosis.
AB  - BACKGROUND: The research of G protein-coupled receptors (GPCRs) is a promising
      strategy for drug discovery. In cancer therapy, there is a need to discover novel
      agents that can inhibit proliferation and induce apoptosis in cancer cells. JTC
      801 is a novel GPCR antagonist with the function of reversing pain and anxiety
      symptoms. This study aims to investigate the antitumor effects of JTC-801 on
      human osteosarcoma cells (U2OS) and elucidate the underlying mechanism. MATERIALS
      AND METHODS: The Cell Counting Kit-8 assay was used to detect the viability of
      U2OS cells treated with JTC-801 in vitro. The cell apoptosis was evaluated using
      a flow cytometry assay with Annexin V-FITC/PI double staining. The inhibitory
      effect of JTC-801 on invasion and migration of U2OS cells were determined by the
      Transwell assays. Western blot assay was performed to measure the levels of
      proteins related to cell apoptosis and its mechanism. RESULTS: The JTC-801
      significantly decreased the viability of U2OS cells (p < .05) as a result of its
      anti-proliferative effect through induction of apoptosis associated with
      activation of BAX, Caspase-3 and down-regulating BCL-2 expression. The invasive
      and migratory cells were obviously reduced after JTC-801 treatment (p < .05).
      Further, the phosphorylated AKT, mTOR and active p70 S6 protein kinase in the
      PI3K/AKT signaling pathway were obviously lessened in the JTC-801 treated U2OS
      group (p < .05). CONCLUSIONS: JTC-801 may exert osteosarcoma cell growth
      inhibition by promoting cell apoptosis, through PI3K/AKT signaling pathway
      participation.

PMID- 29447543
TI  - Unusual sleep experiences and dissociation as mediators between sleep quality and
      proneness to hallucinations in a nonclinical population sample: a preliminary
      study.
AB  - INTRODUCTION: The purpose of this study was to examine the relationship of sleep
      quality to proneness to hallucinations and the mediating role of dissociation and
      unusual sleep experiences in a nonclinical sample. METHODS: One hundred and
      seventy-seven participants completed a questionnaire on sleep quality, a
      dissociative experiences scale, an unusual sleep experiences scale and a
      hallucination proneness scale. RESULTS: The results showed a significant positive
      association between quality of sleep and hallucination proneness, dissociation
      and unusual sleep experiences, and that dissociation and unusual sleep
      experiences fully mediated between sleep quality and hallucination proneness.
      CONCLUSIONS: Our study highlights the importance of variables related to sleep
      quality and unusual sleep experiences and dissociation in understanding
      hallucinations, and the importance of taking these variables into consideration
      in designing intervention directed at reducing distress caused by hallucinations.

PMID- 29447542
TI  - Predictors for orthopaedic surgery in patients with rheumatoid arthritis: results
      from a retrospective cohort study of 1010 patients diagnosed from 1972 to 2009
      and followed up until 2015.
AB  - OBJECTIVES: To investigate how patient characteristics, time of diagnosis, and
      treatment affect the need for orthopaedic surgery in patients with rheumatoid
      arthritis (RA). METHOD: We reviewed the medical history of 1544 patients
      diagnosed with RA at Haukeland University Hospital in Bergen, Norway, from 1972
      to 2009, of whom 1010 (mean age 57 years, 69% women) were included in the present
      study. Relevant orthopaedic procedures were obtained from the Norwegian
      Arthoplasty Register and the hospital's administrative patient records. In total,
      693 procedures (joint synovectomies 22%, arthrodeses 21%, prostheses 41%, and
      forefoot procedures 12%) were performed in 315 patients. Survival analyses were
      completed to evaluate the impact of different factors such as age, gender,
      radiographic changes, and year of diagnosis, on the risk of undergoing surgery.
      RESULTS: Patients diagnosed in 1972-1985 and 1986-1998 had a relative risk of
      undergoing surgery of 2.4 and 2.2 (p < 0.001), respectively, compared to patients
      diagnosed in 1999-2009. Radiographic changes at diagnosis and female gender were
      also significant risk factors. Anti-rheumatic medication was significantly
      different in the three time periods. CONCLUSION: Patients with a diagnosis in the
      early years had a greatly increased risk of having orthopaedic surgery performed.
      This is probably due to the year of diagnosis being a proxy for the type and
      intensity of medical treatment.

PMID- 29447544
TI  - 'Asking' but Not 'Screening': Assessing Physicians' and Nurses' Substance-Related
      Clinical Behaviors.
AB  - BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) is a
      promising public health approach for problematic substance use. A core component
      of SBIRT is the use of formal screening tools to categorize a patient's likely
      level of risk in order to provide an appropriately-matched service. Training in
      formal screening is included in many SBIRT training programs, but infrequently is
      emphasized. OBJECTIVES: To assess pre-training levels of SBIRT-related clinical
      behaviors, including screening, this study examined a secondary dataset collected
      from internal medicine residents and graduate nurse practitioner students.
      METHODS: Learners (n = 117) completed 13 self-report items assessing use of SBIRT
      related behaviors. Researchers used exploratory factor analysis to identify
      underlying concepts in the questionnaire, then used mixed ANOVA to compare mean
      frequency of utilization of each factor (asking, screening, and intervening) by
      academic program. RESULTS: Learners reported asking about substance use
      frequently, intervening some of the time, and infrequently using formal screening
      tools. Interaction and between-academic-program effects were significant but
      small. CONCLUSIONS: Prior to SBIRT training, most clinical practitioners reported
      asking patients about substance use, but few reported regularly using formal
      substance use screening tools. This may have implications for the importance of
      SBIRT training as part of curricular work, and for the internal content foci of
      SBIRT curricula.

PMID- 29447546
TI  - Cancer Prevention Policy Statement Reaffirms ASCO's Antitobacco Stand.

PMID- 29447547
TI  - Personal Finance Management for New Oncologists: Part 1.
AB  - The first article in a two-part series about balancing expenses when you have
      just started a practice.

PMID- 29447545
TI  - Effects of wearing lower leg compression sleeves on locomotion economy.
AB  - The purpose of this investigation was to assess the effect of compression sleeves
      on muscle activation cost during locomotion. Twenty-two recreationally active men
      (age: 25 +/- 3 years) ran on a treadmill at four different speeds (ordered
      sequence of 2.8, 3.3, 2.2, and 3.9 m/s). The tests were performed without
      (control situation, CON) and while wearing specially designed lower leg
      compression sleeves (SL). Myoelectric activity of five lower leg muscles
      (tibialis anterior, fibularis longus, lateral and medial head of gastrocnemius,
      and soleus) was captured using Surface EMG. To assess muscle activation cost, the
      cumulative muscle activity per distance travelled (CMAPD) of the CON and SL
      situations was determined. Repeated measures analyses of variance were performed
      separately for each muscle. The analyses revealed a reduced lower leg muscle
      activation cost with respect to test situation for SL for all muscles (p < 0.05,
      etap2 > 0.18). The respective significant reductions of CMAPD values during SL
      ranged between 4% and 16% and were largest at 2.8 m/s. The findings presented
      point towards an improved muscle activation cost while wearing lower leg
      compression sleeves during locomotion that have potential to postpone muscle
      fatigue.

PMID- 29447548
TI  - A Healthier New Year: Cancer Prevention Information for Your Patients.

PMID- 29447549
TI  - The Genetic Information Nondiscrimination Act: A First Step Toward Protecting
      Americans From Misuse of Genetic Information.
AB  - GINA prohibits health insurers from using an individual's genetic information to
      determine eligibility for insurance or premiums for insurance. Proponents believe
      it will offer protection against discrimination on the basis of genetic
      information, as well as protection against discrimination in employment.

PMID- 29447550
TI  - Generational Differences Among Oncologists: Shaping the Future of Practice.
AB  - According to ASCO's recent workforce study, more than half of today's practicing
      oncologists will be age 65 years or older by the year 2020. As these physicians
      are replaced by a new generation of doctors, what will oncology practice look
      like?

PMID- 29447551
TI  - ASCO Policy Statement Highlights Oncologist's Role in Providing Cancer Prevention
      Services.
AB  - An ASCO Policy Statement has been issued on cancer prevention in an effort to
      heighten awareness of the integral role of oncologists in providing cancer
      prevention services.

PMID- 29447552
TI  - National Coalition for Cancer Survivorship: Advocacy for Quality Cancer Care.

PMID- 29447554
TI  - Cancer.Net: A New Name for ASCO's Patient Information Website.

PMID- 29447553
TI  - Understanding the Finances of Oncology Practice, Part 1.

PMID- 29447555
TI  - Medicare Coding Edits New and Old.

PMID- 29447556
TI  - State Oncology Societies: The Annual Meeting Booth and Accompanying Activities.

PMID- 29447557
TI  - Sink or Swim.

PMID- 29447558
TI  - Succession Planning.

PMID- 29447560
TI  - Marketing the Community Oncology Practice.

PMID- 29447559
TI  - The Use of Practice Consultants.

PMID- 29447561
TI  - Effects of induced sad mood on facial emotion perception in young and older
      adults.
AB  - Older adults perceive less intense negative emotion in facial expressions
      compared to younger counterparts. Prior research has also demonstrated that mood
      alters facial emotion perception. Nevertheless, there is little evidence which
      evaluates the interactive effects of age and mood on emotion perception. This
      study investigated the effects of sad mood on younger and older adults'
      perception of emotional and neutral faces. Participants rated the intensity of
      stimuli while listening to sad music and in silence. Measures of mood were
      administered. Younger and older participants' rated sad faces as displaying
      stronger sadness when they experienced sad mood. While younger participants
      showed no influence of sad mood on happiness ratings of happy faces, older adults
      rated happy faces as conveying less happiness when they experienced sad mood.
      This study demonstrates how emotion perception can change when a controlled mood
      induction procedure is applied to alter mood in young and older participants.

PMID- 29447562
TI  - Overloaded and overlooked: Improving resident advisors' self-care.
AB  - OBJECTIVE: The purpose of this viewpoint is to discuss the lack of research on
      resident advisor (RA) self-care and how behavioral interventions can be used in
      housing programs to educate and improve RA self-care. It is essential for live-in
      housing staff (both professional and paraprofessional) to learn how to develop
      appropriate strategies that target problem behaviors to improve self-care. An
      overview of the RA position, the effects of increased demands (i.e., burnout),
      and the research on self-care behavioral interventions are discussed. Lastly, the
      call to use behavioral interventions within housing programs to educate RAs on
      self-care awareness and improve and monitor their health behaviors to prevent
      burnout and psychological distress is provided.

PMID- 29447565
TI  - 2006 Update of ASCO Recommendations for the Use of Tumor Markers in
      Gastrointestinal Cancer.

PMID- 29447564
TI  - ASCO 2006 Update of the Breast Cancer Follow-Up and Management Guideline in the
      Adjuvant Setting.

PMID- 29447566
TI  - The American Society of Pediatric Hematology/Oncology.

PMID- 29447568
TI  - Employment Contracts: What to Look for.

PMID- 29447567
TI  - What's New With ASCO.org ?

PMID- 29447569
TI  - Performance Evaluations: Honesty Is the Best Policy.

PMID- 29447570
TI  - The Lung Cancer Alliance.

PMID- 29447571
TI  - Patient Guides Help Your Patients Understand ASCO Clinical Practice Guidelines.

PMID- 29447572
TI  - Promising Projects Garner First Awards From the State Affiliate Grant Program.

PMID- 29447573
TI  - The Means Lead to (and justify) the End.

PMID- 29447574
TI  - CAC Network Meeting 2006 Addresses New Initiatives, Current Challenges in
      Medicare Coverage.

PMID- 29447575
TI  - Transitioning to Medicare Administrative Contractors.

PMID- 29447576
TI  - Fending off Cuts to Medicare Imaging Payments.

PMID- 29447577
TI  - The New National Provider Identifier.

PMID- 29447578
TI  - Navigating the Clinical Trial Billing Maze.

PMID- 29447579
TI  - Double gene targeting PCR assay for the detection of Crocodylus porosus in
      commercial products.
AB  - The demand for crocodile meat is quickly growing because of its exotic and
      organoleptic appeal and also the low content of cholesterol and lipids. Moreover,
      crocodile oil and blood have been used in alternative medicines for treating
      asthma and several other ailments since ancient times. Furthermore, crocodile
      hides have great demand in leather industries. All of these have collectively
      contributed to the extensive hunting, illegal trading and consequent decline of
      crocodiles in most parts of the world. To keep space with the growing demands,
      some crocodile species such as Crocodylus porosus have been raised in farms and
      its commercial trades have been legalised. However, demand for wild crocodiles in
      foods and medicines has continued in high gear. Recently, several DNA-based
      methods have been proposed for crocodile detection, but those assays are based on
      single gene and longer-sized amplicon targets that break down during extensive
      processing. To address this gap, here we developed and validated a highly stable
      double gene targeted multiplex PCR assay for the identification of C. porosus
      materials in commercial products. The assay involved two short sites from C.
      porosus atp6 (77 bp) and cytb (127 bp) genes and a universal internal control (99
      bp) for eukaryotes. The PCR primers were cross-tested against 18 species and
      validated under pure and mixed matrices under extensive boiling, autoclaving and
      microwave cooking conditions. Finally, it was used to identify five crocodile
      based commercial products. The lower limits of detection for atp6 and cytb genes
      were 0.001 ng and 0.01 ng DNA, respectively, in pure meat and 1% under mixed
      matrices. Some inherent features, such as 77-127 bp amplicon sizes, exceptional
      stability and superior sensitivity, suggested the assay could be used for the
      identification of C. porosus in any forensic specimen.

PMID- 29447580
TI  - HPLC/PDA determination of carminic acid and 4-aminocarminic acid using relative
      molar sensitivities with respect to caffeine.
AB  - To accurately determine carminic acid (CA) and its derivative 4-aminocarminic
      acid (4-ACA), a novel, high-performance liquid chromatography with photodiode
      array detector (HPLC/PDA) method using relative molar sensitivity (RMS) was
      developed. The method requires no analytical standards of CA and 4-ACA; instead
      it uses the RMS values with respect to caffeine (CAF), which is used as an
      internal standard. An off-line combination of 1H-quantitative nuclear magnetic
      resonance spectroscopy (1H-qNMR) and HPLC/PDA was able to precisely determine the
      RMSs of CA274nm/CAF274nm and 4-ACA274nm/CAF274nm. To confirm the performance of
      the HPLC/PDA method using RMSs, the CA and 4-ACA contents in test samples were
      tested using four different HPLC-PDA instruments and one HPLC-UV. The relative
      standard deviations of the results obtained from five chromatographs and two
      columns were less than 2.7% for CA274nm/CAF274nm and 1.1% for 4
      ACA274nm/CAF274nm. The 1H-qNMR method was directly employed to analyse the CA and
      4-ACA contents in test samples. The differences between the quantitative values
      obtained from both methods were less than 5% for CA and 3% for 4-ACA. These
      results demonstrate that the HPLC/PDA method using RMSs to CAF is a simple and
      reliable quantification method that does not require CA and 4-ACA certified
      reference materials.

PMID- 29447581
TI  - Integrating Models of Diffusion and Behavior to Predict Innovation Adoption,
      Maintenance, and Social Diffusion.
AB  - This study documents an investigation into the adoption and diffusion of eave
      tubes, a novel mosquito vector control, during a large-scale scientific field
      trial in West Africa. The diffusion of innovations (DOI) and the integrated model
      of behavior (IMB) were integrated (i.e., innovation attributes with attitudes and
      social pressures with norms) to predict participants' (N = 329) diffusion
      intentions. The findings showed that positive attitudes about the innovation's
      attributes were a consistent positive predictor of diffusion intentions: adopting
      it, maintaining it, and talking with others about it. As expected by the DOI and
      the IMB, the social pressure created by a descriptive norm positively predicted
      intentions to adopt and maintain the innovation. Drawing upon sharing research,
      we argued that the descriptive norm may dampen future talk about the innovation,
      because it may no longer be seen as a novel, useful topic to discuss. As
      predicted, the results showed that as the descriptive norm increased, the
      intention to talk about the innovation decreased. These results provide broad
      support for integrating the DOI and the IMB to predict diffusion and for efforts
      to draw on other research to understand motivations for social diffusion.

PMID- 29447583
TI  - The profile of a life-saving researcher.
AB  - Research requires different attitudes and skill sets. We should encourage our
      medical students to contribute to research in their own way.

PMID- 29447582
TI  - Clinical characteristics and quality of life in Chinese patients with Parkinson's
      disease beyond 20 years.
AB  - Background The number of Parkinson's disease (PD) patients with disease duration
      of more than 20 years (long disease duration PD, LPD) is on the rise. Objectives
      This study aims to describe the clinical profiles and the quality of life (QoL)
      of LPD patients from a cohort of the Chinese population. Methods We compared 71
      LPD subjects to 60 PD patients who died less than 20 years after the onset of PD
      (control PD, CPD). A regression model was constructed to assess the determinants
      for 20 years survival and the QoL of LPD patients. Results Compared to CPD
      patients, LPD patients exhibited a younger age at disease onset, higher total
      levodopa equivalent daily dose applications, more frequent motor complications,
      lower annual change in Unified PD Rating Scale (UPDRS) III score, as well as
      lower scores for 'sleep/fatigue' and 'mood/apathy' domains and higher score for
      'sexual dysfunction' domain in the Non-Motor Symptom Scale (NMSS) (p < 0.05).
      Multivariate regression analyses indicated that a younger age at disease onset
      (OR = 0.520, 95%CI = 0.295-0.919, p = 0.024), lower annual change in UPDRS III
      score (OR = 0.009, 95%CI = 0.001-0.246, p = 0.005) and lower 'cardiovascular'
      score (OR = 0.552, 95%CI = 0.319-0.955, p = 0.034) were associated with 20-year
      survival, while UPDRS III (beta = 0.320, p < 0.001) and NMSS (beta = 0.549, p <
      0.001) scores were associated with the PD Questionnaire 39 score in LPD.
      Conclusions The age at disease onset, rate of PD deterioration, and
      cardiovascular symptoms are the potential determinants for 20-year survival with
      PD. Both motor and non-motor disturbances contribute to the reduced QoL of LPD
      patients.

PMID- 29447584
TI  - A Longitudinal Qualitative Analysis of the Lived Experience of the Recovery
      Process in Opioid-Dependent Patients Post-Detoxification.
AB  - : The aim of the study was to gain an in-depth understanding of opioid-dependent
      patients' lived experiences post-detoxification. METHOD: The study employed a
      naturalistic, observational longitudinal design, involving baseline screening and
      tracking of patients post-detoxification, with follow-up interviews at three,
      six, and nine months to observe specific processes of interest. This in-depth
      investigation of patients at four points was new within an Irish context and
      novel throughout the literature. FINDINGS: Recovery was seen as a process that
      was not always linear, and lapse and relapse were viewed as part of this process.
      Patients had great insight into "risk factors for relapse," information and
      knowledge gained over several years and many treatment episodes. Furthermore, the
      findings illustrate the role insight plays in any learning and growth experience
      and the emphasis that is placed upon it within the treatment journey; insight is
      a fundamental underpinning to any real growth and development. The current
      article argues that insight merits a more explicit role in the model of recovery
      capital.

PMID- 29447585
TI  - Service seeking experiences of college-aged sexual and intimate partner violence
      victims with a mental health and/or behavioral disability.
AB  - OBJECTIVE: To examine mental health service experiences following sexual violence
      (SV) and intimate partner violence (IPV) victimization among college women with a
      disability. PARTICIPANTS: College women (n = 27, ages 19 to 24) with a disability
      who experienced at least one SV/IPV occurrence; interviewed July/August 2016.
      METHODS: Qualitative study using in-depth interviews, with thematic analysis.
      RESULTS: Women tended to wait several months (or did not seek care at all)
      following SV/IPV, because they downplayed their experience (e.g., not wanting to
      label an experience as "rape"). Those seeking services primarily did so because
      of escalating mental health concerns. Among service seekers, women were satisfied
      when professionals validated their experiences/concerns; and were dissatisfied
      when faced with extended wait time for care and/or professionals unskilled with
      SV/IPV and mental health. However, women still sought care following negative
      experiences. CONCLUSIONS: Improved access to integrated care for SV/IPV and
      mental health, along with skilled professionals, is essential.

PMID- 29447586
TI  - A longitudinal study of interest and membership in a fraternity, rape myth
      acceptance, and proclivity to perpetrate sexual assault.
AB  - OBJECTIVE: This study explored the relation between interest and membership in a
      fraternity and acceptance of sexual violence (eg, rape myth acceptance,
      proclivity to perpetrate sexual aggression) among first year college men.
      PARTICIPANTS: A total of 315 men were surveyed before their first year of college
      (June-August 2010) and again at 4 time points over the next year. METHODS:
      Participants responded to measures of rape myth acceptance and proclivity to
      perpetrate sexual aggression. RESULTS: Interested members scored higher on
      proclivity to perpetrate sexual aggression and some rape myths than noninterested
      nonmembers; interested nonmembers scored in between the 2 groups. CONCLUSIONS:
      Results highlight the importance of considering both fraternity membership and
      interest in joining a fraternity, as well as examining individual rape myths, in
      studies of fraternity membership and sexual violence.

PMID- 29447587
TI  - A photochemically induced fluorescence based flow-through optosensor for
      screening of nitenpyram residues in cruciferous vegetables.
AB  - One of the most used agrochemicals in agricultural production, nitenpyram (NTP),
      has been determined by using a flow-through optosensing device based on
      Photochemically Induced Fluorescence detection. The combination of both
      methodologies allows, on one hand, a quick on-line photodegradation of NTP and,
      on the other hand, the preconcentration, quantification and desorption of the
      fluorescent photoproduct generated when retained on Sephadex QAE-A25 as solid
      support, which was monitored at 295 and 362 nm for excitation and emission,
      respectively. The proposed analytical method presents a detection limit of 500 pg
      mL-1 by using Multicommutated Flow Injection Analysis. Recovery experiments were
      carried out in different kinds of cruciferous vegetables at or below the MRL
      established in Japan, demonstrating that this method combines advantages of
      simplicity, high sensibility and high selectivity, fulfilling the requirements
      for its application in quality control. Results obtained in the analysis of real
      samples were in good agreement with those provided by a reference HPLC method.

PMID- 29447588
TI  - Psychotherapy Termination Practices with Older Adults: Impact of Patient and
      Therapist Characteristics.
AB  - OBJECTIVES: The aims of this study were to survey clinicians' opinions regarding
      psychotherapy practices in mutual termination with a specified population
      (depressed older adult outpatients) and to examine the patient and therapist
      characteristics that may influence such practices. METHODS: We surveyed
      psychologists' (N = 96) psychotherapy termination practices, using a hypothetical
      depressed older adult as a referent, to assess consensus on the appropriateness
      of various guidelines to termination and to examine whether these differ as a
      function of patient and therapist characteristics. RESULTS: Several practices
      were generally agreed to be "extremely appropriate" when terminating
      psychotherapy with older adults, including collaborating to determine the end
      date of treatment and discussing patient growth. Data also indicate that patient
      factors, such as personality pathology, and therapist factors, such as having an
      Integrative theoretical orientation were associated with differential endorsement
      of termination practices. Identification as a geropsychologist or working
      regularly with older adults were associated with a more cautious approach to
      termination. CONCLUSIONS: There is substantial consensus regarding many
      approaches to termination, but modifications might be appropriate depending on
      patient characteristics. CLINICAL IMPLICATIONS: Clinicians agree on a set of
      fundamental termination practices when working with older adults, but modify
      these based on orientation and diagnosis.

PMID- 29447589
TI  - Do student service members/veterans experience worse mental health stigma than
      their peers? A comparative study in a national sample.
AB  - OBJECTIVES: Examine differences in mental health treatment-related stigma in
      student service members and veterans (SSM/Vs) and peers from 57 post-secondary
      institutions across the United States. METHODS: In total, 909 SSM/Vs and 1818
      demographically- and institutionally-matched non-SSM/Vs completed assessments of
      stigma-related barriers to mental health service utilization as part of the
      Healthy Minds Study between 2011 and 2015. RESULTS: When compared to non-SSM/V
      peers, SSM/Vs reported more mental health treatment-related stigma toward help
      seekers and less confidence in the helpfulness of therapy/counseling and
      psychotropic medications. However, effect sizes were small in magnitude (ds = .10
      to .16), and depressed students in both groups reported greater stigma.
      CONCLUSIONS: SSM/Vs experience greater treatment-related stigma than non-SSM/V
      peers, which may deter service use in many cases. However, differences in stigma
      were small and other under-studied barriers to help-seeking may apply to the
      substantive subset of SSM/Vs and non-SSM/Vs who may benefit from utilizing
      available services.

PMID- 29447590
TI  - Correction to: Li, X., Li, W., Shi, Mo, Luo, Qin, Yang and Mo, Is serum bilirubin
      associated with the severity of Guillain-Barre syndrome?

PMID- 29447591
TI  - Characterization of a partial-body irradiation model with oral cavity shielding
      in nonhuman primates.
AB  - PURPOSE: Characterization of a novel partial-body irradiation (PBI) shielding
      strategy in nonhuman primates (NHP; rhesus macaques), aimed at protecting the
      oral cavity, with respect to various gastrointestinal acute radiation syndrome
      (GI-ARS) syndrome parameters as well as buccal ulceration development. MATERIALS
      AND METHODS: NHPs were irradiated using a Cobalt-60 gamma source, in a single
      uniform dose, ranging from 9-13 Gy and delivered at 0.60-0.80 Gy min-1. Animals
      were either partially shielded via oral cavity shielding (PBIOS) or underwent
      total-body irradiation (TBI). RESULTS: Clinical manifestations of GI-ARS, and
      also radiation-induced hematology and clinical chemistry changes, following PBIOS
      were comparable to the PBI NHP GI-ARS model utilizing shielding of the distal
      pelvic limbs and were significantly milder than TBI at similar radiation doses.
      Nadir citrulline levels were comparable between PBIOS and TBI but signs of
      recovery appeared earlier in PBIOS-treated animals. The PBIOS model prevented
      oral mucositis, whereas the TBI model presented buccal ulcerations at all tested
      radiation dose levels. CONCLUSIONS: Taken together, these results suggest that
      the PBIOS model is a suitable alternative to traditional PBI. For GI-ARS
      investigations requiring orally administered medical countermeasures, PBIOS
      confers added value due to the prevention of oral mucositis over traditional PBI.

PMID- 29447600
TI  - Does self-help increase rates of help seeking for student mental health problems
      by minimizing stigma as a barrier?
AB  - OBJECTIVE: This study examined whether self-help (books, websites, mobile apps)
      increases help seeking for mental health problems among college students by
      minimizing stigma as a barrier. PARTICIPANTS AND METHODS: A survey was conducted
      with 200 college students reporting elevated distress from February to April
      2017. RESULTS: Intentions to use self-help were low, but a significant portion of
      students unwilling to see mental health professionals intended to use self-help.
      Greater self-stigma related to lower intentions to seek professional help, but
      was unrelated to seeking self-help. Similarly, students who only used self-help
      in the past reported higher self-stigma than those who sought professional
      treatment in the past. Although stigma was not a barrier for self-help, alternate
      barriers were identified. CONCLUSIONS: Offering self-help may increase rates of
      students receiving help for mental health problems, possibly by offering an
      alternative for students unwilling to seek in-person therapy due to stigma
      concerns.

PMID- 29447601
TI  - Examining the influence of gender and sexual motivation in college hookups.
AB  - OBJECTIVE: Hooking up is common in college, and has been linked to heavy
      drinking. Hookups have positive as well as negative consequences, and thus the
      motivations for hooking up are complex. Yet, little research has focused on these
      motivations. The present study examined the role that gender and drinking
      patterns play in the relationship between sexual motivation and penetrative
      hookups. PARTICIPANTS: Heavy drinking college students (N = 396) completed online
      surveys between September/October 2009. METHOD: Sexual motivation, alcohol, and
      hooking up were assessed. RESULTS: Enhancement motives and drinking frequency
      predicted more frequent oral and vaginal sex when hooking up, while peer and
      partner motives predicted anal sex. Men endorsed greater enhancement motives,
      peer motives, and hookup oral and vaginal sex. For men, coping motives predicted
      oral and vaginal sex and peer motives predicted anal sex. CONCLUSIONS: Results
      provide greater insight into the reasons why college students engage in
      penetrative hookups.

PMID- 29447612
TI  - Urban college student self-report of hookah use with health care providers.
AB  - OBJECTIVE: This study's purpose was to describe urban college students'
      communication about hookah with health care providers. PARTICIPANTS: Participants
      included a random sample of undergraduate urban college students and health care
      providers. METHODS: Students surveyed determined the epidemiology of hookah use
      in this population, how many health care providers asked about hookah, and how
      many students admitted hookah use to a physician. RESULTS: Of 375 students
      surveyed, 78 (20.8%) had never tried it, 284 (75.7%) had smoked hookah at least
      once, and 64 students (22.6%) were classified as frequent hookah smokers. Only 15
      (4.7%) reported a health care provider asking about hookah during visits, whereas
      36 (12.7%) admitted their hookah use to a health care provider. CONCLUSION:
      Hookah use was found to be highly prevalent among students in one urban
      university. This study supports the hypothesis that few health care providers
      broach the topic with patients. Additional research on health consequences of
      hookah use, education, and improved screening is warranted.

PMID- 29447613
TI  - "Who'll do all these if I'm not around?": Bonding social capital and health and
      well-being of inpatients.
AB  - PURPOSE: Although social capital influences health-related decisions and
      behavioural patterns in many developing countries, minimal attention has been
      paid to the nuances of its effect on healthcare. This paper examines how bonding
      social capital affects healthcare delivery for inpatients in Ghana. METHODS: Semi
      structured in-depth interviews were used and thematic analysis method employed to
      analyse the data. Interviews were conducted with health professionals and
      relatives and close friends of inpatients in three public health facilities in
      Ashanti region. RESULTS: Relatives and close friends of inpatients were a
      critical source of instrumental support such as provision of meals, laundry
      services, running errands and financial assistance as well as emotional support.
      These functions-that were both 'expected' and 'encouraged'- reduced the burden on
      the health facilities, which apparently had limited resources to offer adequate
      care. However, the relatives of inpatients sometimes inadvertently obstructed
      efficient healthcare delivery through actions such as extending 'unapproved'
      alternative care to patients. Moreover, the process of contributing towards
      health and well-being of the sick exposed the relatives to health risks due to
      poor living conditions. CONCLUSION: A well-defined and befitting role must be
      devised for at least an immediate social relation of inpatients to improve the
      positive effects of bonding social capital on healthcare delivery.

PMID- 29447615
TI  - Insights into structural features of HDAC1 and its selectivity inhibition
      elucidated by Molecular dynamic simulation and Molecular Docking.
AB  - Histone deacetylases (HDACs) are a family of proteins whose main function is the
      removal of acetyl groups from lysine residues located on histone and non-histone
      substrates, which regulates gene transcription and other activities in cells.
      HDAC1 dysfunction has been implicated in cancer development and progression;
      thus, its inhibition has emerged as a new therapeutic strategy. Two additional
      metal binding sites (Site 1 and Site 2) in HDACs have been described that are
      primarily occupied by potassium ions, suggesting a possible structural role that
      affects HDAC activity. In this work, we explored the structural role of potassium
      ions in Site 1 and Site 2 and how they affect the interactions of compounds with
      high affinities for HDAC1 (AC1OCG0B, Chlamydocin, Dacinostat and Quisinostat) and
      SAHA (a pan-inhibitor) using molecular docking and molecular dynamics (MD)
      simulations in concert with a Molecular-Mechanics-Generalized-Born-Surface-Area
      (MMGBSA) approach. Four models were generated: one with a potassium ion (K+) in
      both sites (HDAC1k), a second with K+ only at site 1 (HDAC1ks1), a third with K+
      only at site 2 (HDAC1ks2) and a fourth with no K+ (HDAC1wk). We found that the
      presence or absence of K+ not only impacted the structural flexibility of HDAC1,
      but also its molecular recognition, consistent with experimental findings. These
      results could therefore be useful for further structure-based drug design studies
      addressing new HDAC1 inhibitors.

PMID- 29447616
TI  - Predictors of positive development in first-year college students.
AB  - OBJECTIVE: Emerging adulthood is an important phase in the transition to
      adulthood. Emerging adults experience minimal social control and incomplete
      development of executive functioning leaving this age-group at risk for misusing
      this newfound independence. Hence, it is important to understand pathways to
      support positive development (PD) outcomes. In this study, we examined the
      relationship between participation in civically engaged learning and PD among
      first-year college students. PARTICIPANTS: First-year college students (N = 225)
      were surveyed during the 2012-2013 academic year. METHODS: Students were surveyed
      on measures of PD and engaged learning prior to the beginning (initial survey)
      and at the end of the first year (final survey) of their undergraduate education.
      Stepwise linear regression was used to examine the influence of engaged learning
      on PD outcomes. RESULTS: Engaged learning during the academic year predicted
      flourishing and students' civic frequency. Also, faith-affiliation and parents'
      civic frequency contributed to students' civic frequency. CONCLUSIONS: Our
      interpretation of the findings suggests that engaged learning and family role
      modeling may promote PD among first-year undergraduate students.

PMID- 29447614
TI  - Adherence and perceived barriers to oral antiviral therapy for chronic hepatitis
      B.
AB  - BACKGROUND: Globally, of the 248 million people chronically infected with the
      hepatitis B virus (HBV), 74 million reside in China. Five oral nucleot(s)ide
      analogs (NUCs) have been approved for the treatment of chronic hepatitis B (CHB)
      in China. OBJECTIVES: The aims of this study were to determine rates of adherence
      to NUC therapy in patients with CHB, to identify the self-perceived barriers to
      adherence, and to examine the factors associated with adherence. METHODS:
      Questionnaire-based interviews were administered among Chinese patients with CHB
      at hepatology clinics of a tertiary hospital in the city of Wuhan, China. Adults
      aged 18 years or older prescribed with NUCs were recruited and interviewed to
      complete a 27-item questionnaire in a private setting, and adherence was measured
      using the Morisky Medication Adherence Scale (MMAS-8). RESULTS: Among 369
      participants, only 16.5% had high adherence (score of 8), 32.2% had medium
      adherence (score of 6 to <8), and 51.2% were measured with low adherence (score
      of <6). A logistic regression model was used to determine the factors associated
      with medication adherence. Significant predictors of high adherence consisted of
      urban residency, non-cirrhotic status, not using prescribed pills other than HBV
      medications, and reminders from family members. The five most common reasons for
      skipping NUCs were that medication(s) are expensive (48.7%), forgetfulness
      (45.1%), have experienced or worry about potential side effects (19.8%), do not
      want others to know about my medication(s) usage (18.5%), and ran out of pills
      and do not have time to refill (15.9%). CONCLUSIONS: This study revealed that
      adherence rates to oral antiviral therapy were far from optimal. This finding
      should generate public attention, and it would be beneficial for interventional
      programs to target Chinese patients from rural regions, as well as patients with
      low socioeconomic status, cirrhosis, and taking multiple medications.

PMID- 29447617
TI  - Experience with Event Timing Does not Alter Emergent Timing: Further Evidence for
      Robustness of Event and Emergent Timing.
AB  - Although, event and emergent timings are thought of as mutually exclusive,
      significant correlations between tapping and circle drawing (Baer, Thibodeau,
      Gralnick, Li, & Penhune, 2013 ; Studenka, Zelaznik, & Balasubramaniam, 2012 ;
      Zelaznik & Rosenbaum, 2010 ) suggest that emergent timing may not be as robust as
      once thought. We aimed to test this hypothesis in both a younger (18-25) and
      older (55-100) population. Participants performed one block of circle drawing as
      a baseline, then six blocks of tapping, followed by circle drawing. We examined
      the use of event timing. Our hypothesis that acute experience with event timing
      would bias an individual to use event timing during an emergent task was not
      supported. We, instead, support the robustness of event and emergent timing as
      independent timing modes.

PMID- 29447618
TI  - Long-term impacts of college sexual assaults on women survivors' educational and
      career attainments.
AB  - OBJECTIVE: To examine the well-documented mental and physical health problems
      suffered by undergraduate women sexually assaulted while on campus with an
      exploration of how the trauma impacts a survivor's lifetime education trajectory
      and career attainment. PARTICIPANTS: In November and December 2015, researchers
      recruited US participants using an online crowdsourcing tool and a Listserv for
      sexual violence prevention and response professionals. METHODS: Of 316 women who
      completed initial screening, 89 qualified to complete a Qualtrics survey. Eighty
      one participants completed the online survey, and 32 participated in phone
      interviews. RESULTS: Ninety-one percent of the participants reported health
      problems related to the assault that they attributed to difficulties they faced
      in their attainment of their education and career goals. CONCLUSIONS: The
      findings suggest the importance of simultaneously examining the effects of human
      capital losses and mental and physical health problems attributed to the costly
      public health problem of campus sexual assault.

PMID- 29447619
TI  - Autism spectrum disorder traits in typically developing emerging adults and
      associated parenting: A person-centered approach.
AB  - Research on parenting children with autism spectrum disorder (ASD) indicates
      these children receive parenting tailored to their condition. However, little is
      known about ASD in adulthood, especially in emerging adults at college, and how
      they are parented. The current study examined how emerging adults in a non
      clinical typically-developing sample differed in their current perceptions of
      parenting as a function of ASD traits. Participants completed questionnaires
      about their current perceptions of parenting and self-reported ASD traits.
      Parenting characteristics assessed included parenting style, discipline, parent
      child relationship quality, and parental distress. Results indicated that higher
      levels of self-reported ASD traits were associated with increasingly ineffective
      parenting characteristics including lower authoritative style, harsher
      discipline, poorer parent-child relationship quality (e.g., lower involvement),
      and higher parental distress. Researchers are encouraged to extend ASD research
      into adulthood by validating diagnostic methods with adults and investigating
      processes in adulthood that have been well-established in the childhood ASD
      literature.

PMID- 29447620
TI  - Using smartphones to collect daily sexual behavior data from college students.
AB  - OBJECTIVE: Our objectives were to measure reporting differences between sexual
      behavior data from daily diary and retrospective estimates and to assess the
      utility of using smartphones to collect sexual behavior data from a college
      student population. PARTICIPANTS: Eighty-six participants (68 women, 18 men)
      completed the study. METHODS: For 30 days during the Spring 2017 semester,
      participants received prompts to participate in daily diaries about their
      previous day's sexual behavior on their smartphones. Participants then
      retrospectively reported their past 30 days of sexual behavior and provided
      feedback on the process of receiving daily diaries on their smartphones. RESULTS:
      We found that college students overreported their sexual behavior on the
      retrospective survey compared to their daily diary reports (ps < .001; Cohen's ds
      >= 1.51). Participants provided positive and constructive feedback. CONCLUSIONS:
      Using smartphones to administer daily diaries is a promising technique for
      obtaining reliable sexual behavior data from college students.

PMID- 29447621
TI  - College students' use of technology to communicate with romantic partners about
      sexual health issues.
AB  - OBJECTIVE: To examine college students' technology-assisted sexual communication
      perceptions and practices alongside their beliefs about the effectiveness of face
      to-face (F-t-F) sexual communication. PARTICIPANTS: 144 college students at a
      private university in the Northeast, U.S., completed a survey in October 2016.
      METHOD: A cross-sectional online survey examined how college students use text
      messaging and private social media messaging to communicate with romantic
      partners about sexual health issues. RESULTS: Students who have communicated with
      romantic partners via technology reported being likely to do so again in the
      future, to perceive the effectiveness of technology-assisted sexual communication
      to be comparable to F-t-F sexual communication, and to be confident in their
      ability to initiate sexual communication with romantic partners via F-t-F
      communication. CONCLUSIONS: College students may see text messaging and social
      media messaging as useful for sexual communication, which has important
      implications for college health professionals who wish to promote frequent,
      effective sexual communication.

PMID- 29447622
TI  - Online readiness assessment for Smoke- and Tobacco-free campus policies.
AB  - OBJECTIVE: Develop and test an online survey to assess campus readiness to adopt
      smoke- and tobacco-free (SF/TF) policies. PARTICIPANTS: Key informants (N = 18)
      at four campuses in Kentucky without a SF/TF policy recruited April 2015.
      METHODS: Cross-sectional design. The survey assessed six dimensions: knowledge
      about SF/TF policies; leadership for campus policy; resources for policy
      development; campus climate surrounding tobacco issues; existing tobacco
      policies; and political climate for campus policy development. Dimension raw
      scores were rescaled to range from 0-1 and summed to determine overall stage of
      readiness (0-6). RESULTS: Political climate was highest dimension across all
      campuses (0.83-1.0). Knowledge dimension ranked lowest (0.0-0.50). Overall
      readiness scores ranged from 2.53-3.94; two campuses in preplanning and two in
      preparation. CONCLUSIONS: Development of the online measure is timely considering
      the impetus to implement SF/TF policies. Findings reinforce that campuses are at
      varying stages of implementing these policies, and stage-based interventions are
      necessary.

PMID- 29447623
TI  - Community health workers on a college campus: Effects on influenza vaccination.
AB  - OBJECTIVE: To assess the impact of a campus community health worker program
      (HealthPALs) on student influenza vaccination. PARTICIPANTS: Undergraduate
      students at a northeastern US university (enrollment 6650), influenza seasons
      2011-2012 through 2015-2016. METHODS: Study design: Difference-in-differences
      analysis of student vaccination at campus dormitory influenza clinics during
      intervention vs. baseline. INTERVENTION: In the first intervention year,
      HealthPALs conducted in-person peer outreach at several campus dormitory flu
      clinics. Subsequent years, HealthPALs conducted an enhanced intervention, with
      the addition of a personalized, dormitory-specific social media campaign
      appealing to students' community identity. RESULTS: The initial intervention
      increased vaccinations by 66% (IRR = 1.66, 95%CI 1.39-1.97) at intervention
      clinics relative to control. The enhanced intervention increased vaccinations by
      85% (IRR = 1.85, 95%CI 1.75-1.96). CONCLUSION: Community health workers can be a
      highly effective, low-cost strategy for increasing influenza vaccination among
      college students. This model could also be used to address other campus health
      challenges where student engagement is key.

PMID- 29447624
TI  - Substance use among students in Thailand.
AB  - This study explored substance use prevalence, level of risk, and associated
      factors, especially related to binge drinking. A cross-sectional study was
      conducted among 306 students using questionnaires and the Alcohol, Smoking, and
      Substance Involvement Screening Test-Youth screening tool. The associations
      between binge drinking and risk factors were analyzed by generalized linear
      models. Our results showed current prevalence rates of alcohol, tobacco, and
      drugs use were 56.9%, 22.9%, and 2.3%, respectively. Multivariate analyses showed
      that being a binge drinker was significantly associated with low self-efficacy,
      high sensation seeking, moderate to high smoking risk, and low grade point
      average.

PMID- 29447625
TI  - Predicting help-seeking behavior: The impact of knowing someone close who has
      sought help.
AB  - OBJECTIVES: This study sought to replicate and extend research on social
      facilitators of college student's help seeking for psychological problems.
      PARTICIPANTS: We collected data on 420 ethnically diverse college students at a
      large public university (September 2008-May 2010). METHODS: Students completed a
      cross-sectional online survey. RESULTS: We found that students who were aware of
      close others' (eg, family, friends) help seeking were two times more likely to
      have sought formal (eg, psychologist) and informal (eg, clergy) help themselves.
      Tests of moderation revealed the incremental effect (ie, controlling for help
      seeking attitudes, internalizing symptoms, cultural demographics) of close
      others' formal help seeking was strong and significant for men (R2 = 0.112),
      while it was negligible and nonsignificant for women (R2 = .002). CONCLUSIONS: We
      discuss the importance for students-particularly men-to learn about close others'
      help seeking for facilitating their own help seeking during times of distress.

PMID- 29447626
TI  - Psoriasis and wound healing outcomes: A retrospective cohort study examining
      wound complications and antibiotic use.
AB  - Little is known about wound healing in psoriasis. We performed a cohort study
      examining differences in wound healing complications between patients with and
      without psoriasis. Psoriasis patients with traumatic wounds were matched 1:3 to
      non-psoriasis patients with traumatic wounds based on age, gender, and body mass
      index (BMI). We examined theincidence of wound complications including infection,
      necrosis, and hematoma as well as incident antibiotic use within three months
      following diagnosis of a traumatic wound. The study included 164 patients with
      traumatic wounds, comprised of 41 patients with psoriasis matched to 123 patients
      without psoriasis. No statistically significant differences were detected in the
      incidence of overall wound complications between wound patients with psoriasis
      and wound patients without psoriasis (14.6% versus. 13.0%, HR 1.18, CI 0.39
      3.56). After adjustment for diabetes, peripheral vascular disease, and smoking,
      no statistically significant differences were detected in the incidence of
      overall wound complications between patients with and without psoriasis (HR 1.11,
      CI 0.34-3.58). Specifically, the adjusted rates of antibiotic use were not
      significantly different between those with and without psoriasis (HR 0.65, CI
      0.29-1.46). The incidence of wound complications following traumatic wounds of
      the skin was found to be similar between patients with and without psoriasis.

PMID- 29447627
TI  - Lynch Syndrome and Muir-Torre Syndrome: An update and review on the genetics,
      epidemiology, and management of two related disorders.
AB  - Hereditary Nonpolyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome,
      is an autosomal dominant, tumor predisposing disorder usuallycaused by germline
      mutations in mismatch repair (MMR) genes. A subset of HNPCC, Muir-Torre Syndrome
      (MTS) also involves MMR gene defects and is generally accepted as a variant of
      HNPCC. MTS is typicallycharacterized by at least one visceral malignancy and one
      cutaneous neoplasm of sebaceous differentiation, with or without
      keratoacanthomas. In either version of the disorder, nonfunctional MMR systems
      lead tothe loss of genomic integrity, marked commonly by mismatches in repetitive
      DNA sequences, resulting in microsatellite instabilities. Deleterious nucleotide
      alterations ultimately drive the process of tumorigenesis in both HNPCC and MTS.
      The following article reviews the epidemiology, genetics, clinical presentation,
      and management of HNPCC and its MTS variant.

PMID- 29447628
TI  - Sexual side effects of 5-alpha-reductase inhibitors finasteride and dutasteride:
      A comprehensive review.
AB  - The 5-alpha-reductase inhibitors finasteride and dutasteride are frequently used
      in the treatment of androgenetic alopecia and benign prostatichyperplasia. These
      drugs are effective at reducing levels of dihydrotestosterone, the primary
      androgen responsible for the pathogenesis of both these conditions. However,
      finasteride and dutasteride have also been shown to produce an increase in the
      incidence of sexual dysfunction, namely, impotence, decreased libido, and
      ejaculation disorder. The purpose of this study is to review the existing medical
      literature with regard to the sexual side effects of 5-alpha-reductase inhibitor
      therapy. This review is an extensive look at the sexual effects of 5-alpha
      reductase inhibitors and compares outcomes for finasteride versus dutasteride in
      addition to comparing sexualside effects for each of the different dosages
      prescribed of finasteride and dutasteride.

PMID- 29447629
TI  - Wilderness dermatology: mountain exposures.
AB  - Exploring the mountains is a highly rewarding past time; however, certain high
      altitude exposures can lead to dermatologic manifestations. In this review
      article, the authors will describe cold, solar, and severe weather that one may
      experience when spending time outdoors. Factors such as increased ultraviolet
      radiation, temperature extremes, and low partial pressure of oxygen, along with
      human physiologic parameters also contribute to disease severity and
      presentation. This review article will address the diagnosis, treatment, and
      prevention of high-altitude dermatology exposures.

PMID- 29447630
TI  - Metformin as an adjunct therapy for the treatment of moderate to severe acne
      vulgaris.
AB  - The purpose of this literature review is to evaluate the use of metformin as an
      adjunct therapy in the treatment of moderate-to-severe acne in those not
      diagnosed with polycystic ovary syndrome (PCOS) or androgen excess. The authors
      conducted independent literature searches. Results were limited to clinical
      trials and randomized controlled trials. Studies with participants diagnosed with
      moderateto-severe acne vulgaris taking metformin versus placebo or other active
      treatment were included;studies with participants diagnosed with PCOS or androgen
      excess were excluded. The authors found three studies consistent with the search
      guidelines that evaluated the effects of metformin as adjunct therapy in moderate
      to severe acne vulgaris. In eachstudy, metformin was an effective adjunct therapy
      in the treatment of moderate-to-severe acne vulgaris.

PMID- 29447631
TI  - Does daily folic acid supplementation reduce methotrexate efficacy?
AB  - Methotrexate is a mainstay treatment for autoimmune and inflammatory conditions
      in the field of Dermatology. However, in some patients, its use is associated
      with significant side effects and toxicity. Folate supplementation with either
      folic acid or folinic acid often mitigates side effects and reduces the incidence
      of systemic toxicity related to methotrexate. Although the value of methotrexate
      is clear, debate remains about folate supplementation. There is little agreement
      about the proper dosing or frequency of folate supplementation as many believe
      that daily folate supplementation can reduce methotrexate efficacy. Although
      daily use of folic acid does not appear to affect methotrexate efficacy, dosing
      of folinic acid close to methotrexate administration may hinder methotrexate
      efficacy. Therefore, folic acid should be used daily with methotrexate to
      ameliorate side effects, whereas folinic acid should only be used for
      methotrexate toxicity.

PMID- 29447632
TI  - Greater distance to an academic medical center is associated with poorer melanoma
      prognostic factors: The University of Colorado Experience.
AB  - INTRODUCTION: Numerous studies report a correlation between distance to
      diagnostic provider in an academic medical center and poorer prognosis ofdisease.
      Limited research on this topic exists with respect to melanoma. METHODS: This was
      a retrospective chart review of 1,463 adults (>=18 years) initially diagnosed
      with melanoma between 2006-2016. Associations between distance traveled and
      Breslow depth and presence of metastatic disease were assessed via cumulative and
      binary logistic regression models, adjusting for patient and tumor
      characteristics. RESULTS: Subjects traveling >=50 miles had 58% greater odds of
      having an increased Breslow depth than those traveling less than that distance
      (OR: 1.58; 95% CI: 1.24-2.01; p<0.0001), and had four times the odds of
      presenting with metastatic disease (OR: 4.04; 95% CI: 3.00-5.46; p<0.0001).
      DISCUSSION: We highlight the correlation between increased distance to our
      academic medical center with greater Breslow depths and the presence ofmetastatic
      disease at presentation. CONCLUSION: Future studies assessing other factors and
      regional differences that limit access to diagnosis might help improve screening
      efforts to prevent poorer prognosis for patients in these areas.

PMID- 29447633
TI  - Modernizing dermatology interest groups in medical school: Certificate programs.
AB  - This commentary addresses the increasingly competitive nature of applying to
      dermatology residency programs and how both interest groups in medical schools
      and their dermatology departments can help to better prepare applicants. As
      previous literature argued that dermatology has been underemphasized in medical
      school curricula, we propose five fundamental options that interest groups can
      implement in order to offer increased exposure to our field in medical training.
      Furthermore, with therecent trend of many schools conferring certificates in
      various specialized concentrations, we also discuss interest groups pioneering
      certificate-grantingprograms in dermatology competency. The pros and cons of
      having a recognized certificate program in dermatology are presented.

PMID- 29447634
TI  - Pityriasis lichenoides-like drug reaction: A clinical histopathologic study of 10
      cases.
AB  - BACKGROUND: Lymphomatoid drug reactions can mimic endogenous T and B cell
      lymphoproliferative diseases. OBJECTIVES: We present a novel form of cutaneous
      drug reaction with features of pityriasis lichenoides (PL), a recognized form of
      T cell dyscrasia. METHODS: Ten cases were studied where a cutaneous eruption
      exhibiting semblance to PL within a few weeks to months after starting a
      particular drug. RESULTS: The patient cohort comprised 7 females and 3 males with
      the mean age of 60 years. Widely distributederythematous cutaneous lesions were
      present in 6 cases whereas a more localized distribution was seen in three cases.
      The most frequently implicated drugsassociated with the eruption were
      antidepressants and statins. Histologic examination showed a morphologic picture
      identical to PL including marked epitheliotropism of mildly atypical lymphocytes,
      psoriasiform epidermal hyperplasia, dyskeratosis, hemorrhage, and a thick
      parakeratotic scale. Therewas a significant reduction in the expression of CD7
      and CD62L amid the T cells. Regression of the eruption occurred in all cases
      excluding one. CONCLUSION: Thefindings conform the categorization of this process
      as a form of T-cell dyscrasia albeit one that is reversible, dependent on the
      drug withdrawal. The limitationof our study includes the retrospective design of
      the study.

PMID- 29447635
TI  - Sublamina densa-type linear IgA bullous dermatosis with IgA autoantibodies
      specific for type VII collagen: a case report and clinicopathological review of
      32 cases.
AB  - Linear IgA bullous dermatosis (LABD) is a rare autoimmune bullous disorder
      characterized by linear deposits of IgA at the basement membrane zone(BMZ) and/or
      by circulating IgA anti-BMZ antibodies. Comparing with other immuno-bullous
      diseases, LABD represents a heterogeneous disease entitywith diversity of
      pathogenic IgA autoantibodies to different hemidesmosomal antigens and an
      association with malignancies and occasional drug use. We herein present an 82
      year-old Japanese man with LABD, whose indirect immunofluorescence using 1M NaCl
      split skin showed positive staining for IgA at the dermal side alone.
      Fluorescence overlay antigen mapping using laser scanning confocal microscopy
      (FOAM-LSCM) was employed to examine the in vivo bound patient's IgA, which was
      specific for type VII collagen (COL7), a prominent antigen of the sublamina
      densa. One year later, he developed malignant lymphoma, suggesting the diagnosis
      of paraneoplastic LABD. We reviewed 32 cases of sublamina-densa type LABD with
      anti-COL7 IgA antibodies thus far reported in the literature to compare the
      clinicopathological characteristics of this rare disease variant and emphasize
      that COL7 is the main autoantigen in sublamina densa disease.

PMID- 29447636
TI  - A diagnostically challenging case of CD8+ primary cutaneous gamma/delta T-cell
      lymphoma.
AB  - Primary cutaneous gamma/delta T-cell lymphoma (PCgammadeltaTCL) is a rare form of
      cutaneous lymphoma characterized by abnormal clonal proliferation of mature,
      activated gamma-delta T cells expressing the gammadelta heterodimer of the T-cell
      receptor (TCR). As an entity, PCgammadeltaTCL has recently undergone diagnostic
      revision since its introduction in the 2008 WHO classification of cutaneous
      lymphomas and confirmedin 2016. Nonetheless, diagnosis remains difficult both
      clinically and histologically, given its broad range of clinical manifestations
      and immunohistochemical phenotypes. Herein, we present a rare case of CD8+
      PCgammadeltaTCL with a discussion highlighting theheterogeneity within this
      entity.

PMID- 29447637
TI  - Crohn disease-associated neutrophilic urticarial dermatosis: report and
      literature review of neutrophilic urticarial dermatosis.
AB  - Neutrophilic urticarial dermatosis (NUD) is a useful diagnostic term for
      urticarial lesions that are less pruritic and more painful than conventional
      urticaria. The histopathologic features include neutrophilic infiltrates in the
      interstitial dermis with a higher density than idiopathic urticaria. NUD has been
      associated with several systemic conditions, which are predominantly autoimmune
      and autoinflammatory in nature. A woman with Crohn disease who developed NUD is
      described. Literature reports of other conditions in which neutrophilic
      urticarial dermatosis have been observed are also reviewed and summarized. NUD
      has not only been described in the setting of inflammatory bowel disease, but
      also in patients who have systemic lupus erythematosus, adult-onset Still
      disease, and IgA gammopathy. NUD is usually associated with an underlying
      disease. Therapeutic agents that target neutrophils (such as dapsone and
      colchicine) and antagonists to interleukin-1 receptor (such as anakinra) may be
      effective modalities for affected patients. NUD can be added to the list of
      dermatologic manifestations associated with systemic inflammation, particularly
      inflammatory bowel disease.

PMID- 29447638
TI  - Pediatric pustular psoriasis responsive to cyclosporine bridged to etanercept: A
      treatment approach.
AB  - Pustular psoriasis occurs rarely in children but can present with acute toxicity
      requiring inpatient admission. For the best approach, medical providers should
      have an evidence based and systematic treatment algorithm in their armamentarium.
      Toillustrate this point, we describe a 13-year-old girl who was admitted with
      generalized pustular psoriasis and who responded dramatically to "wet wrap"
      therapy and cyclosporine bridged to etanercept. Using this case example, we
      highlight the three most important considerations in any patient with new onset
      pustularpsoriasis: avoidance of disease complications, acute "rescue" therapy,
      and maintenance therapy.

PMID- 29447639
TI  - A patient case highlighting the myriad of cutaneous adverse effects of prolonged
      use of hydroxyurea.
AB  - BACKGROUND: Hydroxyurea is an antimetabolite primarily used to treat
      myeloproliferative disorders, and chronic treatment is associated with many
      cutaneous adverse effects ranging in severity from ichthyosis to aggressive
      nonmelanoma skin cancer. CASE PRESENTATION: We report a 67-year-oldman with a
      history of polycythemia vera who was referred for management of progressively
      worsening dorsal hand lesions. The patient presented withhyperpigmentation,
      ichthyosis, plantar keratoderma, dermatomyositis-like eruptions, two squamous
      cell carcinomas, and actinic keratoses. The adversereactions observed were
      acknowledged to be related to chronic hydroxyurea use. The patient underwent Mohs
      excision of the squamous cell carcinomas and thehydroxyurea was promptly
      discontinued; subsequent cutaneous improvement of the dermatomyositislike lesions
      ensued. Another clinically suspicious aggressive squamous cell carcinoma was
      suspected and the patient was referred to the plastic surgery department for
      complete excision because of the size of the lesion. The patient remains on
      periodic dermatology follow up. CONCLUSIONS: We report a case that exemplifies
      the cutaneous adverse effects of chronic hydroxyurea therapy. Although many cases
      improve after drug discontinuation, strict photoprotection and ongoing
      surveillance are indicated given the recently proposed premalignant potential of
      dermatomyositis-like eruptions and the aggressive nature of hydroxyurea-induced
      nonmelanoma skin cancer.

PMID- 29447640
TI  - Classic form of eosinophilic pustular folliculitis in an immunocompetent girl:
      rapid and complete resolution after low-dose oral indomethacin treatment.
AB  - Eosinophilic pustular folliculitis (EPF) is a rare noninfectious pruritic
      dermatosis, first described by Ise and Ofuji in 1965. We report the case of a 15
      year oldimmunocompetent girl that presented with a widespread papulopustular
      eruption four days after her arrival in Japan. The clinical diagnosis of the
      classicform of EPF was confirmed by histological examination of the lesional skin
      that revealed an intense, mainly eosinophilic, dermal infiltrate within and
      aroundpilosebaceous units. Oral administration of lowdose indomethacin (25
      mg/day) led to a complete resolution of the eruption within 6 weeks without
      causing any side effects. The patient is presently completing a 15-month follow
      up and remains free ofrelapses. To the best of our knowledge, it is the first
      time that low-dose oral indomethacin is reported to be capable of causing a rapid
      and complete resolutionof the classic form of EPF.

PMID- 29447641
TI  - Flame figures in linear IgA bullous dermatosis: a novel histopathologic finding.
AB  - BACKGROUND: Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal
      blistering disease usually with a neutrophil rich inflammatory infiltrate, and
      characterized by linear IgA deposition at the basement membrane zone (BMZ), and
      neutrophil predominant dermal inflammation. We report a case of LABD with
      numerous eosinophils and flame figure formation, a unique histopathologic finding
      not previously reported. A 69-year-old woman presented with a rapidly
      progressive, intensely pruritic rash over forearms, breasts, axillae, hips, and
      thighs. Thelesions were comprised of annular vesicles and bullae with hemorrhagic
      crusts and erosions. The clinical differential diagnosis included bullous
      pemphigoid(BP), LABD, and epidermolysis bullosa aquisita (EBA). RESULTS: A biopsy
      from a bullous plaque on the wrist revealed a subepidermal blister with
      neutrophils and numerous eosinophils with flame figure formation.Direct
      immunofluorescent (DIF) microscopy revealed linear deposition of IgA at the BMZ.
      CONCLUSIONS: Although unusual, the combined findings supported a diagnosis of
      LABD. Increased eosinophils may be associated with drug-induced LABD and may
      explain the numerous eosinophils in our case. It is important to be aware of this
      finding as the pathology may easily be misdiagnosed as BP, or possibly
      bullousWells syndrome. This case emphasizes that combined clinical, pathologic,
      and DIF findings are essential in the diagnosis of bullous dermatoses.

PMID- 29447642
TI  - Is it just a psoriasiform dermatitis?
AB  - Bazex syndrome (BS) is a rare paraneoplastic syndrome most frequently associated
      with squamous cell carcinomas of the upper aerodigestive tractand other tumours.
      Characteristically, cutaneous lesions precede the diagnosis of malignancy. We
      report a 72-year-old patient with 1-year history of acral dermatitis. The
      diagnosis of BS was based on the presence of psoriasiform acral dermatitis and
      the evidence of two simultaneous tumors (prostate adenocarcinoma and
      undifferentiated carcinoma ofthe submandibular gland). It is important to have
      this syndrome in mind since cutaneous features usually precede an underlying
      neoplasm.

PMID- 29447643
TI  - A case of leukocytoclastic vasculitis caused by novel anticoagulant rivaroxaban.
AB  - Cutaneous leukocytoclastic vasculitis (LCV) is type of small vessel vasculitis
      that commonly presents as palpable purpura involving the lower extremities and
      buttocks. Approximately half of cases are idiopathic, but the disease may be
      triggered by infection, drug reaction, inflammatory disease, or other causes. We
      report a case of leukocytoclastic vasculitis secondary to the novel anticoagulant
      rivaroxaban (Xarelto(r)).

PMID- 29447644
TI  - Cutaneous metastasis to the scalp as the primary presentation of colorectal
      adenocarcinoma.
AB  - Eruptaneous metastasis is an uncommon presentation of colorectal adenocarcinoma
      that can occur years after diagnosis of the primary cancer or manifest as the
      first sign of malignancy. It is essential to diagnose these metastases
      immediately, as this late-stage development carries a poor prognosis. The scalp
      is one of the less common sites for skin metastases and nodules may be mistaken
      for benign entities. In this case report, we report on the case of a 61-year-old
      woman with CREST syndrome who presented with a cutaneous metastasis to the scalp
      as the first sign ofcolorectal adenocarcinoma.

PMID- 29447645
TI  - Vulvar metastatic Crohn disease: clinical, histopathological and ultrasonographic
      findings.
AB  - Metastatic Crohn disease (MCD) is an unusual type of cutaneous Crohn disease
      characterized by skin lesions separated from the lesions of the gastrointestinal
      tract. The diagnosis of MCD is essentially histological,showing noncaseating
      granulomas in the dermis and subcutaneous fat tissue. We report a case of MCD
      with vulvar involvement and clinical, histopathological, and ultrasonographic
      findings of this disease.

PMID- 29447646
TI  - Lichen amyloidosis of the scalp and forehead.
AB  - Lichen amyloidosis is a subtype of primary localized cutaneous amyloidosis
      (PLCA), which presents as discrete, firm, closely-set 1-3mm, dome-shapedbrown
      papules commonly involving the anterior aspect of shins and extensor surfaces of
      forearms. We present a case of an otherwise healthy man in his 30s with solitary
      facial involvement of lichen amyloidosis, which is very uncommon.

PMID- 29447647
TI  - Association of pemphigus and systemic corticosteroid use with comorbid health
      disorders: A case-control study.
AB  - BACKGROUND: Pemphigus is a group of debilitating autoimmune blistering disorders
      associated with painful blisters of the skin and/or mucous membranes.
      Identification and management of the comorbiditiesof pemphigus is critically
      important to minimize morbidity and decrease mortality. OBJECTIVE: To identify
      the comorbid health conditions of pemphigus vulgaris. METHODS: This was a case
      control study of 130 cases of pemphigus verified by a clinical and laboratory
      diagnosis and 390 age and sex-matched controls with complete follow-up at a large
      metropolitanquaternary care medical center. RESULTS: Pemphigus vulgaris and its
      treatments were significantly associated with type 2 diabetes mellitus (adjusted
      odds ratio [95% confidence interval]: 5.68 [2.93-11.02]), hypertension (2.15
      [1.25-3.71]), osteopenia (10.07 [3.72-27.25]), osteoporosis (4.19 [1.50-11.73]),
      cataracts (7.00 [1.81-27.07]), insomnia (15.00 [1.75-128.39]), and benign
      prostatic hyperplasia (6.84 [1.79-26.18]). A history of taking systemic
      corticosteroids was found in 76% of pemphigus vulgaris patients. There were
      significant statistical interactions between pemphigus vulgaris and a history of
      using systemic corticosteroids as predictors of diabetes mellitus type 2,
      hypertension, osteoporosis, and insomnia. CONCLUSIONS: Safer and more effective
      systemic treatment options are needed for pemphigus to minimize iatrogenic
      complications of disease.

PMID- 29447648
TI  - Dermatology Medical Education: A Multicenter Survey Study of the Undergraduate
      Perspective of the Dermatology Clinical Clerkship.
AB  - BACKGROUND/AIMS: Limited data are available regarding the undergraduate
      dermatology clinical clerkship curriculum in the United States. Our primaryaim is
      to assess medical students' perspectives of the dermatology clinical clerkship.
      METHODS: A multicenter survey study was conducted, which included four California
      dermatology academic programs. A 17-item questionnaire was designed to
      investigate medical student perception with regard tothe overall educational
      value of the various teaching aspects of the dermatology clinical clerkship.
      RESULTS: A total of 152 medical student surveys were completed. Over half of the
      medical students felt proficient in diagnosing the most commondermatologic
      conditions. Eighty-seven percent of medical students were very satisfied with the
      dermatology clerkship. Ninety-one percent of students felt the length of the
      clerkship was appropriate. CONCLUSIONS: The vast majority of medical students
      reported a high level of proficiency in the treatment and diagnosis of common
      skin disorders. In contrast, our findings suggest that medical students may not
      begaining sufficient hands-on experience in conducting certain dermatologic
      procedures following the dermatology clerkship. Overall, medical
      studentperception of the dermatology clinical clerkship was mostly positive.

PMID- 29447649
TI  - A national cross-sectional analysis of dermatology away rotations using the
      Visiting Student Application Service database.
AB  - The highly competitive nature of the dermatology match requires applicants to
      undertake a variety of measures in the hopes of securing a residency position.
      Among the opportunities available to applicants is the chance to participate in
      away or "audition" rotations during their final year of undergraduate medical
      education. Away rotations are now performed by a majority of medical students
      applying into dermatology, but littleresearch has been done to describe the
      nature of this opportunity for interested applicants. An analysis of all
      dermatology electives offered in the Visiting Student Application Service (VSAS)
      database wasperformed. Results indicate that students have the option to pursue
      electives in a variety of subjects offered by 100 sponsoring institutions spread
      across a wide geographic distribution. Although manyopportunities exist, this
      analysis sheds light on several areas for improving the quality of this
      experience for interested applicants, including providing more electives in
      advanced subject matter, permitting more flexibility in scheduling, and promoting
      wider participation in VSAS.

PMID- 29447650
TI  - Characteristics of research tracks in dermatology residency programs: a national
      survey.
AB  - Pursuing research is encouraged in dermatology residency programs. Some programs
      offer specific research or investigative tracks. Currently, there is little data
      on the structure or scope of research tracks in dermatology residency programs.
      An anonymous online survey was distributed to the Association of Professors of
      Dermatology listserve in 2016. Program directors of dermatology residency
      programs in the United States were asked to participate and 38 of the 95 program
      directors responded. The survey results confirmed that a 2+2 research track,
      which is two years of clinical training followed by two years of research, was
      the most common investigator trackmodel and may promote an academic career at the
      resident's home institution. Further studies will help determine the most
      effective research track models to promote long-term outcomes.

PMID- 29447651
TI  - Elective time during dermatology residency: A survey of residents and program
      directors.
AB  - Elective time during residency training provides residents with exposure to
      different subspecialties. This opportunity gives residents the chance tonurture
      growth in particular areas of interest and broaden their knowledge base in
      certain topics in dermatology by having the chance to work withexperts in the
      field. The purpose of this study was to assess the views of residency program
      directors and dermatology residents on the value of elective time through a cross
      sectional survey. An eight-questionIRB exempt survey was sent out to 113
      residency program directors via email through the American Professors of
      Dermatology (APD) program director listserv. Program directors were asked to
      forward a separate set of 9 questions to their residents. The majority of
      programs that responded allowed for some elective time within their schedule,
      often duringthe PGY 4 (3rd year of dermatology training), but the amount of time
      allowed widely varied among many residency programs. Overall, residents and
      program directors agree that elective is important in residencytraining, but no
      standardization is established across programs.

PMID- 29447652
TI  - Pyoderma gangrenosum, acne, and suppurative hidradenitis syndrome in end-stage
      renal disease successfully treated with adalimumab.
AB  - PASH syndrome (pyoderma gangrenosum, acne, and suppurative hidradenitis) forms
      part of the spectrum of autoinflammatory diseases. We report an unusual case of
      PASH syndrome in a patient with end-stagerenal disease (ESRD) who was
      successfully treated with the tumor necrosis factor inhibitor, adalimumab. The
      case underscores the challenges associatedwith the treatment of PASH syndrome as
      well as the ongoing search to establish a genetic basis for the syndrome. Renal
      impairment has been reported in association with pyoderma gangrenosum but has
      notbeen described in PASH syndrome. We believe this to be the first reported case
      of a patient who developed PASH syndrome in the setting of ESRD.

PMID- 29447653
TI  - Rituximab and intravenous immunoglobulin as alternatives to long-term systemic
      corticosteroids in the treatment of pemphigus: a single center case series of 63
      patients.
AB  - Rituximab and intravenous immunoglobulin [IVIg] have recently emerged as
      effective treatments for pemphigus refractory to corticosteroids [CS]. This case
      series sought to compare the clinical, serologic,and adverse effects of CS, IVIg,
      and rituximab in patients with pemphigus. A retrospective review of 63 patients
      with pemphigus vulgaris (PV), pemphigus foliaceus (PF), or paraneoplastic
      pemphigus (PNP)was performed. Clinical remission (CR), serologic remission (SR),
      and adverse effects were evaluated. Three study groups were compared: patients
      treated with systemic CS, refractory patients treated withIVIg, and refractory
      patients treated with rituximab. The overall number of adverse effects was not
      significantly different between the groups but those observed in patients treated
      with systemic CS weremore severe. CR was less likely in the patients treated with
      systemic CS than in patients treated with IVIg or rituximab, P-value = 0.000467.
      SR was more likely in patients treated with systemic CS or rituximab thanin
      patients treated with IVIg, P-value = 0.002118. These results suggest that the
      clinical efficacy of IVIg is not correlated with an expected concomitant SR.
      Frequently reserved for refractory pemphigus,IVIg and rituximab are significantly
      more likely to produce clinical remission than systemic CS therapy, suggesting
      their utility as first-line treatments.

PMID- 29447654
TI  - Papular mucinosis, or localized lichen myxedematosis (LM) (discrete papular
      type).
AB  - Lichen myxedematosus is condition characterized by localized areas of dermal
      deposition of mucin, presenting with firm papules localized to few areas of the
      body. The condition needs to be excluded from scleromyxedema, which, in addition
      to the firm papular eruption, has areas of induration and is usually associated
      with a monoclonal gammopathyand systemic symptoms. We present a 62-year-old woman
      with a several-year history of asymptomatic, firm papules over the face and arms
      with no evidence of thyroid disease or a monoclonal gammopathy,which is
      consistent with a diagnosis of localized lichen myxedematosus, the discrete
      papular variant. The patient is being treated with a topical
      calcineurininhibitor.

PMID- 29447655
TI  - Epidermolysis bullosa acquisita.
AB  - Epidermolysis bullosa acquisita (EBA) is a rare, acquired subepidermal blistering
      disease. EBA is characterized by autoantibodies to collagen VII,which serves to
      link the epidermis to the dermis. The two most common presentations of EBA are
      classical noninflammatory EBA and bullous pemphigoid-like EBA. Diagnosis of EBA
      can be challenging as it sharesclinical and histopathologic features with other
      blistering diseases. Treatment is often recalcitrant and will often necessitate
      multiple therapies. We presenta case of a thirty-six-year-old Chinese man with
      EBA and review the literature.

PMID- 29447656
TI  - Local heat urticaria.
AB  - We present a 38-year-old woman with local heat urticaria confirmed by heat
      provocation testing. Heat urticaria is a rare form of physical urticaria that
      istriggered by exposure to a heat source, such as hot water or sunlight. Although
      it is commonly localized and immediate, generalized and delayed onset forms
      exist. Treatment options include antihistamines and heat desensitization. A
      brisk, mechanical stroke elicited a linear wheal. Five minutes after exposure to
      hot water, she developed well-demarcated,erythematous blanching wheals that
      covered the distal forearm and entire hand.

PMID- 29447657
TI  - Generalized hyperhidrosis secondary to presumed eccrine gland dysfunction with
      possible apocrine metaplasia.
AB  - We present a 57 year-old man presented with generalized hyperhidrosis and
      widespread, smooth, flesh colored papules on the torso and
      extremities.Histological examination from multiple biopsies demonstrated
      morphologic alteration of the eccrine glands with an apocrine phenotype,
      suggesting eitherapocrine metaplasia or the presence of "apoeccrine glands." The
      morphologic similarities between eccrine, apocrine, and apoeccrine as they relate
      to ourpatient's histologic findings are discussed. We consider secondary causes
      of generalized hyperhidrosis, which may also play a role in this patient's
      presentation. Treatment and further workup are discussed, whilemanagement of this
      patient remains in progress.

PMID- 29447658
TI  - Primary anetoderma with undifferentiated connective tissue disease.
AB  - Anetoderma is a rare benign elastolytic disorder that is characterized by focal
      loss of elastin fibers on histopathology and is often recalcitrant to treatment.
      We present a case of a patient with a 20-year history of pruritic and painful
      hyperpigmented atrophic papules clustered on the neck, axillae, inframammary
      folds, and right medial thigh. Although the histopathologyof her axillary lesions
      was consistent with anetoderma, her clinical presentation is unusual given the
      extent of involvement, reported pain and pruritus, and sharp demarcation of the
      distribution. The diagnosticuncertainty of this case led to added difficulty in
      management of a disease that is already notoriously difficult to treat and may
      significantly impact patient's quality of life.

PMID- 29447659
TI  - Paraneoplastic Pemphigus in a 34-year-old.
AB  - Paraneoplastic Pemphigus (PNP) is a rare and often fatal autoimmune mucocutaneous
      blistering disease associated with an underlying malignancy. It is thought to be
      caused by antibodies to tumor antigenscross-reacting with epithelial antigens,
      specifically desmosomal and hemidesmosomal antigens. There are at least five
      clinical morphologic variants of PNP, with the earliest and most consistent
      finding beingsevere stomatitis. Diagnosis of PNP requires direct
      immunofluorescence of perilesional skin and indirect immunofluorescence.
      Treatment of PNP is difficult and largely limited to glucocorticoids, steroid
      sparing immunomodulators, rituximab and intravenous immunoglobulin (IVIG).
      Despite therapies, prognosis is poor. We report a case of paraneoplastic
      pemphigus in a 34-year old male with severe stomatitis and lichenplanus-like
      cutaneous lesions.

PMID- 29447660
TI  - Expanded carrier screening: what the reproductive endocrinologist needs to know.
AB  - Expanded carrier screening refers to identification of carriers of single-gene
      disorders outside of traditional screening guidelines. New genetic testing
      technologies allow for such screening at costs that are comparable to single-gene
      testing. There is a high degree of variability among genetic testing laboratories
      as to the inclusion of different disorders, some of which have mild or
      unpredictable phenotypes. This review discusses the pros and cons of using
      expanded carrier screening in the preconceptional patient and reviews guidelines
      currently endorsed by professional organizations.

PMID- 29447661
TI  - Ethical quandaries around expanded carrier screening in third-party reproduction.
AB  - Although current screening methods of gamete donors are capable of reducing the
      incidence of genetic anomalies in donor offspring below general population
      levels, targeted screening for a large number of conditions (expanded carrier
      screening or ECS) could be considered as part of the routine selection procedure
      for gamete donors. There are, however, important drawbacks to its practical
      implementation. Excluding all carriers of severe recessive monogenic pediatric
      disorders would disqualify virtually all donors, and other approaches negatively
      affect cost (and therefore access), present dilemmas in regard to disclosure of
      genetic findings, and/or overburden the intended parents. In all of the scenarios
      considered, adequate genetic counseling will be of central importance. Besides
      looking at benefits and drawbacks of possible ways of implementing ECS, we also
      examine whether a moral obligation exists to adopt ECS at all and on whose
      shoulders such an alleged obligation would rest: policymakers, medical staff at
      fertility clinics, sperm and egg banks, the intended parents? We argue that given
      the small risk reduction brought about by ECS, the possible negative effects of
      its implementation, and the absence of widespread preconception carrier screening
      in the general population, it is inconsistent to argue that there is a moral
      obligation to perform ECS in the context of donor conception. Finally,
      implications for the donors are discussed.

PMID- 29447662
TI  - Cell-free DNA for the detection of fetal aneuploidy.
AB  - Screening for fetal aneuploidy via cell-free DNA was described more than two
      decades ago and has been used clinically by obstetric providers in the United
      States for more than 5 years. Cell-free DNA affords excellent detection of fetal
      Down syndrome and other common aneuploidies and thus is sought by patients and
      providers. However, owing to the source of the DNA and the nature of the
      screening test, scenarios may arise that require expert counseling about complex
      issues regarding fetal and maternal health, test interpretation, and management.
      It is essential that infertility specialists understand the specific issues
      related to the strengths and limitations of this screening test, especially in
      light of expanded genetic testing of embryos.

PMID- 29447664
TI  - Prevention of in vitro fertilization twins should focus on maximizing single
      embryo transfer versus twins are an acceptable complication of in vitro
      fertilization.

PMID- 29447663
TI  - Prenatal diagnosis by chromosomal microarray analysis.
AB  - Chromosomal microarray analysis (CMA) is performed either by array comparative
      genomic hybridization or by using a single nucleotide polymorphism array. In the
      prenatal setting, CMA is on par with traditional karyotyping for detection of
      major chromosomal imbalances such as aneuploidy and unbalanced rearrangements.
      CMA offers additional diagnostic benefits by revealing sub-microscopic imbalances
      or copy number variations that are too small to be seen on a standard G-banded
      chromosome preparation. These submicroscopic imbalances are also referred to as
      microdeletions and microduplications, particularly when they include specific
      genomic regions that are associated with clinical sequelae. Not all
      microdeletions/duplications are associated with adverse clinical phenotypes and
      in many cases, their presence is benign. In other cases, they are associated with
      a spectrum of clinical phenotypes that may range from benign to severe, while in
      some situations, the clinical significance may simply be unknown. These scenarios
      present a challenge for prenatal diagnosis, and genetic counseling prior to
      prenatal CMA greatly facilitates delivery of complex results. In prenatal
      diagnostic samples with a normal karyotype, chromosomal microarray will diagnose
      a clinically significant subchromosomal deletion or duplication in approximately
      1% of structurally normal pregnancies and 6% with a structural anomaly. Pre-test
      counseling is also necessary to distinguish the primary differences between the
      benefits, limitations and diagnostic scope of CMA versus the powerful but limited
      screening nature of non-invasive prenatal diagnosis using cell-free fetal DNA.

PMID- 29447665
TI  - Preparation of molecularly imprinted polymer nanobeads for selective sensing of
      carboxylic acid vapors.
AB  - The detection and discrimination of volatile carboxylic acid components, which
      are the main contributors to human body odor, have a wide range of potential
      applications. Here, a quartz crystal microbalance (QCM) sensor array based on
      molecularly imprinted polymer (MIP) nanobeads is developed for highly sensitive
      and selective sensing of typical carboxylic acid vapors, namely: propionic acid
      (PA), hexanoic acid (HA) and octanoic acid (OA). The MIP nanobeads were prepared
      by precipitation polymerization with methacrylic acid (MAA) as a functional
      monomer, trimethylolproane trimethacrylate (TRIM) as a crosslinker, and
      carboxylic acids (PA, HA and OA) as the template molecules. The precipitation
      polymerization resulted in nano-sized (150-200 nm) polymer beads with a regular
      shape. The polymerization conditions were optimized to give a functional monomer,
      crosslinker, and template ratio of 1:1:2. We investigated the imprinting effect
      using both QCM and GC/MS measurements comparing vapor absorption characteristics
      between the imprinted and non-imprinted (NIP) nanobeads. A four-channel QCM
      sensory array based on the NIP and the three types of MIP nanobeads was
      fabricated for sensing the three types of carboxylic acid vapor at concentrations
      on the ppm level. The output of the sensor array was analyzed by both a non
      supervised method (principle component analysis: PCA) and supervised method
      (linear discrimination analysis: LDA). LDA showed a better discrimination ability
      than PCA. A 96%-classification rate was achieved by applying leave-one-out cross
      validation to the LDA model. The high sensitivity and selectivity of the sensor
      array was attributed to the imprinting effect of the nano-sized polymer beads.
      The developed MIP nanobeads, together with other types of MIPs, show promise as
      materials for artificial receptors in vapor and odorant sensing.

PMID- 29447666
TI  - Trace determination of antimony by hydride generation atomic absorption
      spectrometry with analyte preconcentration/atomization in a dielectric barrier
      discharge atomizer.
AB  - Atomization conditions for antimony hydride in the plasma atomizer based on a
      dielectric barrier discharge (DBD) with atomic absorption spectrometric detection
      were optimized. Argon was found as the best discharge gas under a flow rate of 50
      mL min- 1 while the DBD power was optimum at 30 W. Analytical figures of merit
      including interference study of As, Se and Bi have been subsequently investigated
      and the results compared to those found in an externally heated quartz tube
      atomizer (QTA). The limit of detection (LOD) reached in DBD (0.15 ng mL-1 Sb) is
      comparable to that observed in QTA (0.14 ng mL-1 Sb). Finally, possibility of Sb
      preconcentration by stibane in situ trapping in a DBD atomizer was studied. For
      trapping time of 300 s, the preconcentration efficiency and LOD, respectively,
      were 103 +/- 2% and 0.02 ng mL-1.

PMID- 29447667
TI  - Feature expansion by a continuous restricted Boltzmann machine for near-infrared
      spectrometric calibration.
AB  - A modified algorithm for training a restricted Boltzmann machine (RBM) has been
      devised and demonstrated for improving the results for partial least squares
      (PLS) calibration of wheat and meat by near-infrared (NIR) spectroscopy. In all
      cases, the PLS calibrations improved by using the abstract features generated
      from the RBM so long as the nonlinear mapping increased the dimensionality. The
      evaluations were validated using bootstrapped Latin partitions (BLPs) with 5
      bootstraps and 3-Latin partitions which proved useful because of the statistical
      learning and random initial conditions of the RBM networks. By using a noise
      decay parameter, initial large amounts of noise could be used and the benefits of
      simulated annealing achieved as the noise level is slowly decreased. This paper
      demonstrates for the first time that using abstract features and enlarging the
      spectral data can improve the calibration results and exemplifies the Copiosity
      Principle. Two NIR reference datasets were evaluated. The first set of wheat
      spectra was calibrated for protein concentration and the second set of meat
      spectra was calibrated for moisture, fat, and protein concentration. The RBM
      feature extraction improved the linearity of the models and reduced embedded
      noise. The RBM also can help eliminate some difficult spectral preprocessing
      stages such as variable alignment and feature selection. RBMs benefit from
      derivative preprocessing of the NIR spectra or other preprocessing that enhances
      the differences among the spectra.

PMID- 29447668
TI  - A simple and automated sample preparation system for subsequent halogens
      determination: Combustion followed by pyrohydrolysis.
AB  - A simple and automated system based on combustion followed by a pyrohydrolysis
      reaction was proposed for further halogens determination. This system was applied
      for digestion of soils containing high (90%) and also low (10%) organic matter
      content for further halogens determination. The following parameters were
      evaluated: sample mass, use of microcrystalline cellulose and heating time. For
      analytes absorption, a diluted alkaline solution (6 mL of 25 mmol L-1 NH4OH) was
      used in all experiments. Up to 400 mg of soil with high organic matter content
      and 100 mg of soil with low organic matter content (mixed with 400 mg of
      cellulose) could be completely digested using the proposed system. Quantitative
      results for all halogens were obtained using less than 12 min of sample
      preparation step (about 1.8 min for sample combustion and 10 min for
      pyrohydrolysis). The accuracy was evaluated using a certified reference material
      of coal and spiked samples. No statistical difference was observed between the
      certified values and results obtained by the proposed method. Additionally, the
      recoveries obtained using spiked samples were in the range of 98-103% with
      relative standard deviation values lower than 5%. The limits of quantification
      obtained for F, Cl, Br and I for soil with high (400 mg of soil) and low (100 mg
      of soil) organic matter were in the range of 0.01-2 MUg g-1 and 0.07-59 MUg g-1,
      respectively. The proposed system was considered as a simple and suitable
      alternative for soils digestion for further halogens determination by ion
      chromatography and inductively coupled plasma mass spectrometry techniques.

PMID- 29447669
TI  - Highly sensitive glucose sensor based on monodisperse palladium nickel/activated
      carbon nanocomposites.
AB  - Glucose enzyme biosensors have been used for a variety of applications such as
      medical diagnosis, bioprocess engineering, beverage industry and environmental
      scanning etc. and there is still a growing interest in glucose sensors. For this
      purpose, addressed herein, as a novel glucose sensor, highly sensitive activated
      carbon (AC) decorated monodisperse nickel and palladium alloy nanocomposites
      modified glassy carbon electrode (Ni-Pd@AC/GCE NCs) have been synthesized by in
      situ reduction technique. Raman Spectroscopy (RS), X-ray Photoelectron
      Spectroscopy (XPS), X-ray Diffraction (XRD), Transmission Electron Microscopy
      (TEM), cyclic voltammetry (CV) and chronoamperometry (CA) were used for the
      characterization of the prepared non-enzymatic glucose sensor. The characteristic
      sensor properties of the Ni-Pd@AC/GCE electrode were compared with Ni-Pd NCs/GCE,
      Ni@AC/GCE and Pd@AC/GCE and the results demonstrate that the AC is very effective
      in the enhancement of the electrocatalytic properties of sensor. In addition, the
      Ni-Pd@AC/GCE nanocomposites showed a very low detection limit of 0.014 MUM, a
      wide linear range of 0.01 mM-1 mM and a very high sensitivity of 90 mA mM-1 cm-2.
      Furthermore, the recommended sensor offer the various advantageous such as facile
      preparation, fast response time, high selectivity and sensitivity. Lastly,
      monodisperse Ni-Pd@AC/GCE was utilized to detect glucose in real sample species.

PMID- 29447670
TI  - Rapid screening of basic colorants in processed vegetables through mass
      spectrometry using an interchangeable thermal desorption electrospray ionization
      source.
AB  - Thermal desorption electrospray ionization/mass spectrometry (TD-ESI-MS)
      employing a quickly interchangeable ionization source is a relatively new ambient
      ionization mass spectrometric technique that has had, to date, only a limited
      number of applications related to food safety control. With reallocation of
      resources, this direct-analysis technique has had wider use in food analysis when
      operated in dual-working mode (pretreatment-free qualitative screening and
      conventional quantitative confirmation) after switching to an ambient ionization
      source from a traditional atmospheric pressure ionization source. Herein, we
      describe the benefits and challenges associated with the use of a TD-ESI source
      to detect adulterants in processed vegetables (PVs), as a proof-of-concept for
      the detection of basic colorants. While TD-ESI can offer direct qualitative
      screening analyses for PVs with detection capabilities lower than those provided
      with liquid chromatography/UV detection within 30 s, the use of TD-ESI for semi
      quantification is applicable only for homogeneous food matrices.

PMID- 29447671
TI  - Label-free and sensitive microRNA detection based on a target recycling
      amplification-integrated superlong poly(thymine)-hosted copper nanoparticle
      strategy.
AB  - Poly(thymine)-hosted copper nanoparticles (poly T-CuNPs) have emerged as a
      promising label-free fluorophore for bioanalysis, but its application in RNA
      related studies is still rarely explored. Herein, by utilizing duplex-specific
      nuclease (DSN) as a convertor to integrate target recycling mechanism into
      terminal deoxynucleotidyl transferase (TdT)-mediated superlong poly T-CuNPs
      platform, a specific and sensitive method for microRNA detection has been
      developed. In this strategy, a 3'-phosphorylated DNA probe can hybridize with
      target RNA and then be cut by DSN to produce 3'-hydroxylated fragments, which can
      be further tailed by TdT with superlong poly T for fluorescent CuNPs synthesis.
      As proof of concept, an analysis of let-7d was achieved with a good linear
      correlation between 20 and 1000 pM (R2 = 0.9965) and a detection limit of 20 pM.
      Moreover, both homologous and heterologous microRNAs were also effectively
      discriminated. This strategy might pave a brand-new way for designing label-free
      and sensitive microRNA assays.

PMID- 29447672
TI  - Formulation of DNA chimera templates: Effects on emission behavior of silver
      nanoclusters and sensing.
AB  - Single strand DNA (ssDNA) chimeras consisting of a silver nanoclusters-nucleating
      sequence (NC) and an aptamer are widely employed to synthesize functional silver
      nanoclusters (AgNCs) for sensing purpose. Despite its simplicity, this chimeric
      templated AgNCs often leads to undesirable turn-off effect, which may suffer from
      false positive signals caused by interference. In our effort to elucidate how the
      relative position of NC and aptamer affects the fluorescence behavior and sensing
      performance, we systematically formulated these NC and aptamer regions at
      different position in a DNA chimera. Using adenosine aptamer as a model, we
      tested the adenosine-induced optical response of each design. We also
      investigated the effect of linker region connecting NC and aptamer, as well as
      different NC sequence on the sensing performance. We concluded that locating NC
      sequence at 5'-end exhibited the best response, with immediate fluorescence
      enhancement observed over a wide linear range (1-2500 MUM). Our experimental
      findings help to explain the emission behavior and sensing performance of
      chimeric conjugates of AgNCs, providing an important means to formulate a better
      aptasensor.

PMID- 29447673
TI  - A regenerated "turn on" fluorescent probe for sulfide detection in live cells and
      read samples based on dihydroxyhemicyanine-Cu2+ dye.
AB  - A novel "turn-on" fluorescence probe (HHC)2-Cu2+ for sulfide (S2-) was
      synthesized and characterized based on dihydroxyhemicyanine-Cu2+ complex. The
      probe displayed high sensitivity and selectivity for S2- over other analytes,
      including biothiols, NaCN, reactive oxygen species (ROS) and reactive nitrogen
      species (RNS) in aqueous solution, which was attributed to the large association
      constant and the fast kinetics of precipitation of CuS. The probe (HHC)2-Cu2+ can
      be regenerated and reversibly detected with S2- with a remarkable red-fluorescent
      change by alternating the addition of S2- and Cu2+. Fluorescent spectra of (HHC)2
      Cu2+ toward S2- showed a high selectivity, a good linearity, a low limit of
      detection at 0.12 MUM, a rapid response time (less than 30 s), and a wide pH
      range of 7-10. Importantly, the probe was successfully applied to detect the low
      level of S2- in waste water samples, corrupt blood samples, and living cells.

PMID- 29447674
TI  - Green-modified micellar liquid chromatography for isocratic isolation of some
      cardiovascular drugs with different polarities through experimental design
      approach.
AB  - Bilayer pseudo-stationary phase micellar liquid chromatography (MLC) was
      developed for simultaneous isocratic isolation of hydrochlorothiazide, as a basic
      polar (hydrophilic) cardiovascular drug, as well as triamterene and losartan
      potassium, as acidic-nonpolar (hydrophobic) cardiovascular drugs. Utilizing a
      deep eutectic solvent (DES), as a novel green mobile phase additive in
      combination with acetonitrile (ACN) and acetic acid (ACA), drastically improved
      the chromatographic behavior of the drugs. Concentration of sodium dodecyl
      sulphate (SDS), as well as volume percentages of ACN, DES, and ACA were optimized
      by using a central composite design. The optimal composition of the mobile phase
      (0.12 mol L-1 SDS, 5% ACN, 4% DES, and 2% ACA) was chosen through the
      desirability function. The chromatographic peaks of both hydrophilic and
      hydrophobic drugs, respectively, emerged at high and low retention time values in
      the shortest total analysis time of 20 min (at a flow rate of 2 mL min-1).
      Analytical characterization of the developed approach was investigated through
      Food and Drug Administration (FDA) guidelines. Applicability of the method was
      evaluated by analysing of human plasma samples which were directly injected into
      the system.

PMID- 29447675
TI  - Quantitative determination of non-lactose milk oligosaccharides.
AB  - A method for the determination of non-lactose oligosaccharides (NLO) in milk
      using liquid chromatography has been developed. Oligosaccharides were labelled
      with a fluorescent tag, 2-aminobenzamide (2AB), and were identified by comparison
      of their retention times to those of oligosaccharide standards, their mass (as
      measured by mass spectrometry) and their fragmentation patterns in the mass
      spectrometer. The concentrations of the NLO in milk have been determined using 2
      different approaches: (1) by preparing a calibration curve using genuine
      standards of each oligosaccharide. (2) by preparing a calibration curve using
      maltotriose as a universal standard for all NLO, and assuming all 2AB labelled
      oligosaccharides give an equimolar response in the detector. The accuracy of the
      method was assessed by spike-recovery experiments. Using genuine NLO standards
      for calibration, recoveries were in the range 96-114%. Using maltotriose as a
      universal calibrant, recoveries were in the range 86-120%. Method precision was
      assessed by determining the relative standard deviation of the results under
      repeatability (RSD(r)) and intermediate reproducibility (RSD(iR)) conditions. In
      most cases RSD(r) and RSD(iR) were below 5% irrespective of calibration method,
      but increased when NLO levels were close to LoQ.

PMID- 29447676
TI  - Referral patterns to an osteoporosis clinic for dermatology patients undergoing
      prolonged corticosteroid therapy.

PMID- 29447677
TI  - An open-label exploratory study evaluating the efficacy and safety of ingenol
      mebutate gel 0.05% for the treatment of verruca vulgaris.

PMID- 29447678
TI  - Frontal fibrosing alopecia and cutaneous comorbidities: A potential relationship
      with rosacea.

PMID- 29447679
TI  - The microbial flora of taxane therapy-associated nail disease in cancer patients.

PMID- 29447680
TI  - Satisfaction with care and likelihood to recommend ratings attributed to
      dermatology trainees.

PMID- 29447681
TI  - A cross-sectional study of YouTube videos about atopic dermatitis.

PMID- 29447682
TI  - To fee or not to fee? The ethical issues of concierge medicine/dermatology.

PMID- 29447683
TI  - The ethics of medical marijuana in dermatology.

PMID- 29447684
TI  - Crown vessels and follicular white dot: New dermoscopic findings in a case of
      solitary reticulohistiocytoma.

PMID- 29447685
TI  - Response to: "Maintenance of Certification: A grandfatherly ethical analysis".

PMID- 29447686
TI  - Reply to: "The microbial flora of taxane therapy-associated nail disease in
      cancer patients".

PMID- 29447687
TI  - In response to Lebwohl et al, "Psychiatric adverse events during treatment with
      brodalumab: Analysis of psoriasis clinical trials".

PMID- 29447688
TI  - Reply to: "Psychiatric adverse events during treatment with brodalumab: Analysis
      of psoriasis clinical trials".

PMID- 29447689
TI  - Botulinum Neurotoxins: Still a Privilege of Clostridia?
AB  - Botulinum neurotoxins (BoNTs) are potent bacterial toxins mostly produced by
      genetically diverse clostridial strains. Recently, BoNT variants have been
      reported in non-clostridial strains. In this issue of Cell Host & Microbe, Zhang
      et al. (2018) describe a novel BoNT in Entecoccus faecium.

PMID- 29447690
TI  - Autophagy: Suicide Prevention Hotline for the Gut Epithelium.
AB  - Autophagy is genetically associated with inflammatory bowel disease (IBD);
      however, its role remains unclear in disease pathogenesis. Three recent studies
      reveal a novel cytoprotective role of autophagy during viral, bacterial, and
      protozoan-triggered IBD (Burger et al., 2018; Matsuzawa-Ishimoto et al., 2017;
      Pott et al., 2018).

PMID- 29447691
TI  - A Balancing Act: PGRPs Preserve and Protect.
AB  - How does the immune system maintain a balance between preserving a beneficial
      microbiome and protecting against pathogens while also inducing effective, yet
      not damaging, responses? In this issue of Cell Host & Microbe, Charroux et al.
      (2018) reveal that, in Drosophila, this task is performed by three isoforms of
      PGRP-LB, a peptidoglycan-hydrolyzing amidase.

PMID- 29447692
TI  - Less Is Best in the Convergent Evolution of Typhoidal Salmonella.
AB  - Related works in this issue of Cell Host & Microbe (Bronner et al., 2018) and in
      a recent issue of Cell Reports (Hiyoshi et al., 2018) demonstrate how loss-of
      function mutations in butyrate utilization and lipopolysaccharide O-antigen
      processing contribute to evasion of innate host defenses and the convergent
      evolution of distinct typhoidal Salmonella lineages.

PMID- 29447693
TI  - Infectious Scarring: Setting the Trigger for Intestinal Inflammation.
AB  - The initiating factors that trigger inflammatory bowel disease (IBD) are poorly
      understood. In a recent paper, Yang et al. (2017) demonstrate that IBD-like
      syndrome in mice can develop as a consequence of recurrent pathogen infection.
      Pathogenic triggering of inflammatory disease is a re-emerging concept that has
      significant therapeutic implications.

PMID- 29447694
TI  - An Additive Sugar Helps the C. diff Go Round.
AB  - Outbreaks of hypervirulent strains of Clostridium difficile began to be reported
      in healthcare facilities worldwide around 20 years ago. Concurrently, trehalose
      became a common additive used by the global food industry. A new study provides
      evidence that these two observations are a linked phenomenon (Collins et al.,
      2018).

PMID- 29447695
TI  - Cervicovaginal Microbiota and Reproductive Health: The Virtue of Simplicity.
AB  - Cervicovaginal microbiota play a critical role in women's health and reproductive
      outcomes. Despite being one of the simplest commensal bacterial communities in
      the human body, we are only beginning to appreciate its complex dynamic nature
      and important role in host immune modulation. In this review, we discuss the
      "optimal" cervicovaginal bacterial community composition, the impact of
      microbiota on gynecologic and obstetric outcomes, and the hurdles to developing a
      deeper mechanistic understanding of the function of the cervicovaginal
      microbiome. We then describe efforts to durably alter microbial composition in
      this compartment by promotion of Lactobacillus colonization with probiotics,
      modulation of vaginal pH, hormonal administration, and the eradication of
      pathogenic bacteria with antibiotics. Finally, we draw on lessons learned from
      the deeply investigated gut microbiome to suggest future avenues of research into
      host-pathogen interactions in the female genital tract.

PMID- 29447696
TI  - Strain Tracking Reveals the Determinants of Bacterial Engraftment in the Human
      Gut Following Fecal Microbiota Transplantation.
AB  - Fecal microbiota transplantation (FMT) from healthy donor to patient is a
      treatment for microbiome-associated diseases. Although the success of FMT
      requires donor bacteria to engraft in the patient's gut, the forces governing
      engraftment in humans are unknown. Here we use an ongoing clinical experiment,
      the treatment of recurrent Clostridium difficile infection, to uncover the rules
      of engraftment in humans. We built a statistical model that predicts which
      bacterial species will engraft in a given host, and developed Strain Finder, a
      method to infer strain genotypes and track them over time. We find that
      engraftment can be predicted largely from the abundance and phylogeny of bacteria
      in the donor and the pre-FMT patient. Furthermore, donor strains within a species
      engraft in an all-or-nothing manner and previously undetected strains frequently
      colonize patients receiving FMT. We validated these findings for metabolic
      syndrome, suggesting that the same principles of engraftment extend to other
      indications.

PMID- 29447697
TI  - Herpes Simplex Virus 1 VP22 Inhibits AIM2-Dependent Inflammasome Activation to
      Enable Efficient Viral Replication.
AB  - The AIM2 inflammasome is activated by DNA, leading to caspase-1 activation and
      release of pro-inflammatory cytokines interleukin 1beta (IL-1beta) and IL-18,
      which are critical mediators in host innate immune responses against various
      pathogens. Some viruses employ strategies to counteract inflammasome-mediated
      induction of pro-inflammatory cytokines, but their in vivo relevance is less well
      understood. Here we show that the herpes simplex virus 1 (HSV-1) tegument protein
      VP22 inhibits AIM2-dependent inflammasome activation. VP22 interacts with AIM2
      and prevents its oligomerization, an initial step in AIM2 inflammasome
      activation. A mutant virus lacking VP22 (HSV-1DeltaVP22) activates AIM2 and
      induces IL-1beta and IL-18 secretion, but these responses are lost in the absence
      of AIM2. Additionally, HSV-1DeltaVP22 infection results in diminished viral
      yields in vivo, but HSV-1DeltaVP22 replication is largely restored in AIM2
      deficient mice. Collectively, these findings reveal a mechanism of HSV-1 evasion
      of the host immune response that enables efficient viral replication in vivo.

PMID- 29447699
TI  - A Case of Death Resulting from the Complications of a Rudimentary Uterine Horn
      Pregnancy.

PMID- 29447698
TI  - Genetic Ablation of Butyrate Utilization Attenuates Gastrointestinal Salmonella
      Disease.
AB  - Salmonella enterica serovar (S.) Typhi is an extraintestinal pathogen that
      evolved from Salmonella serovars causing gastrointestinal disease. Compared with
      non-typhoidal Salmonella serovars, the genomes of typhoidal serovars contain
      various loss-of-function mutations. However, the contribution of these genetic
      differences to this shift in pathogen ecology remains unknown. We show that the
      ydiQRSTD operon, which is deleted in S. Typhi, enables S. Typhimurium to utilize
      microbiota-derived butyrate during gastrointestinal disease. Unexpectedly,
      genetic ablation of butyrate utilization reduces S. Typhimurium epithelial
      invasion and attenuates intestinal inflammation. Deletion of ydiD renders S.
      Typhimurium sensitive to butyrate-mediated repression of invasion gene
      expression. Combined with the gain of virulence-associated (Vi) capsular
      polysaccharide and loss of very-long O-antigen chains, two features
      characteristic of S. Typhi, genetic ablation of butyrate utilization abrogates S.
      Typhimurium-induced intestinal inflammation. Thus, the transition from a
      gastrointestinal to an extraintestinal pathogen involved discrete genetic
      changes, providing insights into pathogen evolution and emergence.

PMID- 29447700
TI  - Un cas de deces decoulant des complications d'une grossesse dans une corne
      uterine rudimentaire.

PMID- 29447701
TI  - Mullerian Anomaly With Pelvic Pain.

PMID- 29447702
TI  - Anomalie mullerienne avec douleur pelvienne.

PMID- 29447703
TI  - The Importance to Exclude the Existence of a Rudimentary Uterine Horn in Women
      with Unicornuate Uterus.

PMID- 29447704
TI  - L'importance d'ecarter l'existence d'une corne uterine rudimentaire chez les
      femmes presentant un uterus unicorne.

PMID- 29447705
TI  - Excerpts from the World Medical Literature.

PMID- 29447706
TI  - La Litterature Medicale Mondiale.

PMID- 29447707
TI  - Questioning Some Recommendations in the Umbilical Cord Blood Guideline.

PMID- 29447709
TI  - Letter to the Editor: Female Nutrition.

PMID- 29447708
TI  - Author Response: Delayed Cord Clamping and Umbilical Cord Blood Collection.

PMID- 29447710
TI  - Author Response: Guideline Clarification.

PMID- 29447711
TI  - No. 355-Physiologic Basis of Pain in Labour and Delivery: An Evidence-Based
      Approach to its Management.
AB  - OBJECTIVE: To review the evidence relating to nonpharmacological approaches in
      the management of pain during labour and delivery. To formulate recommendations
      for the usage of nonpharmacological approaches to pain management. OPTIONS:
      Nonpharmacological methods available for pain management during labour and
      delivery exist. These should be included in the counselling and care of women.
      EVIDENCE: PubMed and Medline were searched for articles in French and English on
      subjects related to "breastfeeding," "pain," "epidural," "anaesthesia,"
      "analgesia," "labour," "labor," and combined with "gate control theory,"
      "alternative therapies," "massage," "position," "mobility," "TENS," "bathing,"
      "DNIC," "acupuncture," "acupressure," "sterile water injection," "higher center,"
      "control mind," "cognitive structuring," "holistic health," "complementary
      therapy(ies)," "breathing," "relaxation," "mental imagery," "visualization,"
      "mind focusing," "hypnosis," "auto-hypnosis," "sophrology," "mind and body
      interventions," "music," "odors," "biofeedback," "Lamaze," "Bonapace," "prenatal
      training," "gymnastic," "chanting," "haptonomy," "environment," "transcutaneous
      electrical stimulus-stimulation," "antenatal education," "support," "continuous
      support," "psychosocial support," "psychosomatic medicine," "supportive care,"
      "companion," "intrapartum care," "nurse," "midwife(ves)," "father," "doula,"
      "caregiver," " hormones," "oxytocin," "endorphin," "prolactin," "catecholamine,"
      "adrenaline," and "noradrenaline" from 1990 to December 2015. Additional studies
      were identified by screening reference lists from selected studies and from
      expert suggestions. No language restrictions were applied. VALIDATION METHODS:
      The quality of the evidence is rated using the criteria described in the Report
      of the Canadian Task Force on Preventive Health Care. Recommendations for
      practice are ranked according to the method described in this report. BENEFITS,
      RISKS, AND COST: The nonpharmacological method encourages an incremental approach
      to pain management that contributes to reduced interventions through optimal use
      of the woman's neurophysiologic and endocrine resources and a better
      understanding of the physiology of stress and pain during labour. GUIDELINE
      UPDATE: The guideline will be reviewed 5 years after publication to decide
      whether all of part of the guideline should be updated. However, if important new
      evidence is published prior to the 5-year cycles, the review process may be
      accelerated for a more rapid update of some recommendations. SPONSORS: This
      guideline was developed with resources funded by The Society of Obstetricians and
      Gynaecologists of Canada. SUMMARY STATEMENTS: RECOMMENDATIONS.

PMID- 29447712
TI  - N degrees  355-Fondements physiologiques de la douleur pendant le travail et
      l'accouchement: approche de soulagement basee sur les donnees probantes.

PMID- 29447713
TI  - Correction.

PMID- 29447714
TI  - Correction.

PMID- 29447715
TI  - No 163- Prise en charge gynecologique et obstetricale des femmes presentant une
      coagulopathie hereditaire.

PMID- 29447716
TI  - No. 186-Conservative Management of Urinary Incontinence.
AB  - OBJECTIVE: To outline the evidence for conservative management options for
      treating urinary incontinence. OPTIONS: Conservative management options for
      treating urinary incontinence include behavioural changes, lifestyle
      modification, pelvic floor retraining, and use of mechanical devices. OUTCOMES:
      To provide understanding of current available evidence concerning efficacy of
      conservative alternatives for managing urinary incontinence; to empower women to
      choose continence therapies that have benefit and that have minimal or no harm.
      EVIDENCE: The Cochrane Library and Medline (1966 to 2005) were searched to find
      articles related to conservative management of incontinence. Review articles were
      appraised. VALUES: The quality of evidence is rated, and recommendations are made
      using the criteria described by the Canadian Task Force on Preventive Health
      Care. BENEFITS, HARMS, COSTS: Evidence for the efficacy of conservative
      management options for urinary incontinence is strong. These options can be
      advocated as primary interventions with minimal or no harm to women.
      RECOMMENDATIONS: 

PMID- 29447717
TI  - No 186-Prise en charge conservatrice de l'incontinence urinaire.

PMID- 29447718
TI  - No. 240-Cytomegalovirus Infection in Pregnancy.
AB  - OBJECTIVES: To review the principles of prenatal diagnosis of congenital
      cytomegalovirus (CMV) infection and to describe the outcomes of the affected
      pregnancies. OUTCOMES: Effective management of fetal infection following primary
      and secondary maternal CMV infection during pregnancy. Neonatal signs include
      intrauterine growth restriction (IUGR), microcephaly, hepatosplenomegaly,
      petechiae, jaundice, chorioretinitis, thrombocytopenia and anemia, and long-term
      sequelae consist of sensorineural hearing loss, mental retardation, delay of
      psychomotor development, and visual impairment. These guidelines provide a
      framework for diagnosis and management of suspected CMV infections. EVIDENCE:
      Medline was searched for articles published in English from 1966 to 2009, using
      appropriate controlled vocabulary (congenital CMV infection) and key words
      (intrauterine growth restriction, microcephaly). Results were restricted to
      systematic reviews, randomized controlled trials/controlled clinical trials, and
      observational studies. Searches were updated on a regular basis and incorporated
      into the guideline. Grey (unpublished) literature was identified through
      searching the websites of health technology assessment and health technology
      assessment-related agencies, clinical practice guideline collections, clinical
      trial registries, and national and international medical specialty societies.
      RECOMMENDATIONS: The quality of evidence reported in this document has been
      assessed using the evaluation of evidence criteria in the Report of the Canadian
      Task Force on Preventive Health Care (Table 1).

PMID- 29447719
TI  - No 240-Infection a cytomegalovirus pendant la grossesse.

PMID- 29447720
TI  - No. 257-Ultrasonographic Cervical Length Assessment in Predicting Preterm Birth
      in Singleton Pregnancies.
AB  - OBJECTIVES: To review (1) the use of ultrasonographic-derived cervical length
      measurement in predicting preterm birth and (2) interventions associated with a
      short cervical length. OUTCOMES: Reduction in rates of prematurity and/or better
      identification of those at risk, as well as possible prevention of unnecessary
      interventions. EVIDENCE: Published literature was retrieved through searches of
      PubMed and The Cochrane Library up to December 2009, using appropriate controlled
      vocabulary and key words (preterm labour, ultrasound, cervix, incompetent cervix,
      transvaginal, transperineal, cervical length, fibronectin). Results were
      restricted to general and systematic reviews, randomized controlled
      trials/controlled clinical trials, and observational studies. There were no date
      or language restrictions. Grey (unpublished) literature was identified through
      searching the websites of health technology assessment and health technology
      assessment-related agencies, clinical practice guideline collections, clinical
      trial registries, and national and international medical specialty societies.
      VALUES: The evidence and this guideline were reviewed by the Diagnostic Imaging
      Committee and the Maternal Fetal Medicine Committee of the Society of
      Obstetricians and Gynaecologists of Canada, and the recommendations were made
      according to the guidelines developed by The Canadian Task Force on Preventive
      Health Care (Table 1). BENEFITS, HARMS, AND COSTS: Preterm birth is a leading
      cause of perinatal morbidity and mortality. Use of the ultrasonographic technique
      reviewed in this guideline may help identify women at risk of preterm birth and,
      in some circumstances, lead to interventions that may reduce the rate of preterm
      birth. SPONSORS: The Society of Obstetricians and Gynaecologists of Canada
      SUMMARY STATEMENTS: RECOMMENDATIONS.

PMID- 29447721
TI  - No 257-Recours a l'evaluation echographique de la longueur cervicale pour predire
      l'accouchement preterme dans le cadre de grossesses monofoetales.

PMID- 29447722
TI  - No. 276-Management of Group B Streptococcal Bacteriuria in Pregnancy.
AB  - OBJECTIVE: To provide information regarding the management of group B
      streptococcal (GBS) bacteriuria to midwives, nurses, and physicians who are
      providing obstetrical care. OUTCOMES: The outcomes considered were neonatal GBS
      disease, preterm birth, pyelonephritis, chorioamnionitis, and recurrence of GBS
      colonization. EVIDENCE: Medline, PubMed, and the Cochrane database were searched
      for articles published in English to December 2010 on the topic of GBS
      bacteriuria in pregnancy. Bacteriuria is defined in this clinical practice
      guideline as the presence of bacteria in urine, regardless of the number of
      colony-forming units per mL (CFU/mL). Low colony counts refer to <100 000 CFU/mL,
      and high (significant) colony counts refer to >=100 000 CFU/mL. Results were
      restricted to systematic reviews, randomized controlled trials, and relevant
      observational studies. Searches were updated on a regular basis and incorporated
      in the guideline to February 2011. Grey (unpublished) literature was identified
      through searching the websites of health technology assessment and health
      technology assessment-related agencies, clinical practice guideline collections,
      clinical trial registries, and national and international medical specialty
      societies. VALUES: Recommendations were quantified using the evaluation of
      evidence guidelines developed by the Canadian Task Force on Preventive Health
      Care (Table). BENEFITS, HARMS, AND COSTS: The recommendations in this guideline
      are designed to help clinicians identify pregnancies in which it is appropriate
      to treat GBS bacteriuria to optimize maternal and perinatal outcomes, to reduce
      the occurrences of antibiotic anaphylaxis, and to prevent increases in antibiotic
      resistance to GBS and non-GBS pathogens. No cost-benefit analysis is provided.
      RECOMMENDATIONS: 

PMID- 29447723
TI  - No 276-Prise en charge de la bacteriurie a streptocoques du groupe B pendant la
      grossesse.

PMID- 29447724
TI  - No. 127-The Evaluation of Stress Incontinence Prior to Primary Surgery.
AB  - OBJECTIVE: To provide clinical guidelines for the evaluation of women with stress
      urinary incontinence prior to primary anti-incontinence surgery. OPTIONS: The
      modalities of evaluation range from basic pelvic examination through to the use
      of adjuncts including ultrasound and urodynamic testing. OUTCOMES: These
      guidelines provide a comprehensive approach to the preoperative evaluation of
      urinary incontinence to ensure that excessive evaluation is avoided without
      sacrificing diagnostic accuracy. EVIDENCE: Published opinions of experts,
      supplemented by evidence from clinical trials, where appropriate. VALUES: The
      quality of the evidence is rated using the criteria described by the Canadian
      Task Force on the Periodic Health Examination. BENEFITS, HARMS, AND COSTS:
      Comprehensive evaluation of women considering surgery to treat urinary
      incontinence is essential to rule out causes of incontinence that may not be
      amenable to surgical treatment. Simplifying the evaluation minimizes the
      discomfort and embarrassment potentially experienced by women. RECOMMENDATIONS:
      VALIDATION: These guidelines have been approved by the Urogynaecology Committee
      and the Executive and Council of The Society of Obstetricians and Gynaecologists
      of Canada.

PMID- 29447725
TI  - No 127-Evaluation de l'incontinence d'urine a l'effort en vue d'une intervention
      chirurgicale primaire.

PMID- 29447726
TI  - No. 129-Exercise in Pregnancy and the Postpartum Period.
AB  - OBJECTIVE: To design Canadian guidelines advising obstetric care providers of the
      maternal, fetal, and neonatal implications of aerobic and strength-conditioning
      exercises in pregnancy. OUTCOMES: Knowledge of the impact of exercise on
      maternal, fetal, and neonatal morbidity, and of the maternal measures of fitness.
      EVIDENCE: MEDLINE search from 1966 to 2002 for English language articles related
      to studies of maternal aerobic and strength conditioning in a previously
      sedentary population, maternal aerobic and strength conditioning in a
      previouslyactive population, impact of aerobic and strength conditioning on early
      and late pregnancy outcomes, and impact of aerobic and strength conditioning on
      neonatal outcomes, as well as for review articles and meta-analyses related to
      exercise in pregnancy. VALUES: The evidence collected was reviewed by the Society
      of Obstetricians and Gynaecologists of Canada (SOGC Clinical Practice Obstetrics
      Committee) with representation from the Canadian Society for Exercise Physiology,
      and quantified using the evaluation of evidence guidelines developed by the
      Canadian Task Force on the Periodic Health Exam. RECOMMENDATIONS: VALIDATION:
      This guideline has been approved by the SOGC Clinical Practice Obstetrics
      Committee, the Executive and Council of SOGC, and the Board of Directors of the
      Canadian Society for Exercise Physiology. SPONSORS: This guideline has been
      jointly sponsored by The Society of Obstetricians and Gynaecologists of Canada
      and the Canadian Society for Exercise Physiology.

PMID- 29447727
TI  - No 129-L'exercice physique pendant la grossesse et le postpartum.
AB  - OBJECTIF: Enoncer une directive canadienne visant a informer les fournisseurs de
      soins obstetricaux des repercussions, pour la mere, le foetus et le nouveau-ne,
      des exercices de conditionnement aerobique et musculaire pendant la grossesse.
      ReSULTATS ATTENDUS: Effets sur la morbidite maternelle, foetale et neonatale et
      mesures de la forme physique maternelle. PREUVES: Une recherche sur MEDLINE des
      articles, publies en anglais de 1966 a 2002, appartenant aux categories suivantes
      : etudes sur le conditionnement aerobique et musculaire chez des femmes ne
      faisant pas jusque-la d'exercice et chez des femmes actives avant leur grossesse,
      ainsi que des etudes sur les repercussions du conditionnement aerobique et
      musculaire sur les issues precoces et tardives de la grossesse ou sur les issues
      neonatales; rapports de synthese et meta-analyses portant sur l'exercice pendant
      la grossesse. VALEURS: Les resultats recueillis ont ete revus par la Societe des
      obstetriciens et gynecologues du Canada (Comite de la pratique clinique -
      obstetrique), avec la participation de la Societe canadienne de physiologie de
      l'exercice, et ils ont ete classes suivant les criteres d'evaluation des preuves
      etablis par le Groupe de travail canadien sur l'examen de sante periodique.
      RECOMMANDATIONS: VALIDATION: Cette directive a ete approuvee par le Comite de
      pratique clinique - obstetrique de la SOGC, par le Comite executif et par le
      Conseil de la SOGC, ainsi que par le Conseil d'administration de la Societe
      canadienne de physiologie de l'exercice. PARRAINe PAR: la Societe des
      obstetriciens et gynecologues du Canada et par la Societe canadienne de
      physiologie de l'exercice.

PMID- 29447728
TI  - No. 148-Guidelines for Operative Vaginal Birth.
AB  - OBJECTIVE: To provide guidelines for operative vaginal birth in the management of
      the second stage of labour. OPTIONS: Non-operative techniques, episiotomy, and
      Caesarean section are compared to operative vaginal birth. OUTCOME: Reduced fetal
      and maternal morbidity and mortality. EVIDENCE: MEDLINE and Cochrane databases
      were searched using the key words ''vacuum" and "birth" as well as "forceps" and
      "birth" for literature published in English from january 1970 to June 2004. The
      level of evidence and quality of rec-ommendations made are described using the
      Evaluation of Evidence from the Canadian Task Force on the Periodic Health
      Examination. RECOMMENDATIONS: VALIDATION: The Clinical Practice Obstetrics
      Committee and Executive and Council of the Society of Obstetricians and
      Gynaecologists of Canada approved these guidelines.

PMID- 29447729
TI  - No 148-Directive clinique sur l'accouchement vaginal operatoire.

PMID- 29447730
TI  - No. 163-Gynaecological and Obstetric Management of Women With Inherited Bleeding
      Disorders.
AB  - OBJECTIVE: The prevalence of bleeding disorders, notably von Willebrand disease
      (vWD), among adult women with objectively documented menorrhagia is consistently
      reported to be 10% to 20% and is even higher in adolescents presenting with
      menorrhagia. OPTIONS: Diagnostic tools and specific medical and, where
      appropriate, surgical alternatives to management are reviewed and evidence-based
      recommendations presented. EVIDENCE: A MEDLINE search of the English literature
      between January 1975 and November 2003 was performed using the following key
      words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital
      bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives,
      medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal.
      Recommendations from other society guidelines were reviewed. VALUES: The quality
      of evidence reported in this document has been described USing the Evaluation of
      Evidence criteria outlined in the Report of the Canadian Task Force on the
      Preventive Health Exam (Table 1).13 RECOMMENDATIONS.

PMID- 29447732
TI  - Left Ventricular Noncompaction: From Physiologic Remodeling to Noncompaction
      Cardiomyopathy.

PMID- 29447731
TI  - Genetics, Clinical Features, and Long-Term Outcome of Noncompaction
      Cardiomyopathy.
AB  - BACKGROUND: The clinical outcomes of noncompaction cardiomyopathy (NCCM) range
      from asymptomatic to heart failure, arrhythmias, and sudden cardiac death.
      Genetics play an important role in NCCM. OBJECTIVES: This study investigated the
      correlations among genetics, clinical features, and outcomes in adults and
      children diagnosed with NCCM. METHODS: A retrospective multicenter study from 4
      cardiogenetic centers in the Netherlands classified 327 unrelated NCCM patients
      into 3 categories: 1) genetic, with a mutation in 32% (81 adults; 23 children) of
      patients; 2) probably genetic, familial cardiomyopathy without a mutation in 16%
      (45 adults; 8 children) of patients; or 3) sporadic, no family history, without
      mutation in 52% (149 adults; 21 children) of patients. Clinical features and
      major adverse cardiac events (MACE) during follow-up were compared across the
      children and adults. RESULTS: MYH7, MYBPC3, and TTN mutations were the most
      common mutations (71%) found in genetic NCCM. The risk of having reduced left
      ventricular (LV) systolic dysfunction was higher for genetic patients compared
      with the probably genetic and sporadic cases (p = 0.024), with the highest risk
      in patients with multiple mutations and TTN mutations. Mutations were more
      frequent in children (p = 0.04) and were associated with MACE (p = 0.025). Adults
      were more likely to have sporadic NCCM. High risk for cardiac events in children
      and adults was related to LV systolic dysfunction in mutation carriers, but not
      in sporadic cases. Patients with MYH7 mutations had low risk for MACE (p = 0.03).
      CONCLUSIONS: NCCM is a heterogeneous condition, and genetic stratification has a
      role in clinical care. Distinguishing genetic from nongenetic NCCM complements
      prediction of outcome and may lead to management and follow-up tailored to
      genetic status.

PMID- 29447733
TI  - Stroke Risk in Patients With Reduced Ejection Fraction After Myocardial
      Infarction Without Atrial Fibrillation.
AB  - BACKGROUND: Stroke can occur after myocardial infarction (MI) in the absence of
      atrial fibrillation (AF). OBJECTIVES: This study sought to identify risk factors
      (excluding AF) for the occurrence of stroke and to develop a calibrated and
      validated stroke risk score in patients with MI and heart failure (HF) and/or
      systolic dysfunction. METHODS: The datasets included in this pooling initiative
      were derived from 4 trials: CAPRICORN (Effect of Carvedilol on Outcome After
      Myocardial Infarction in Patients With Left Ventricular Dysfunction), OPTIMAAL
      (Optimal Trial in Myocardial Infarction With Angiotensin II Antagonist Losartan),
      VALIANT (Valsartan in Acute Myocardial Infarction Trial), and EPHESUS (Eplerenone
      Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study);
      EPHESUS was used for external validation. A total of 22,904 patients without AF
      or oral anticoagulation were included in this analysis. The primary outcome was
      stroke, and death was treated as a "competing risk." RESULTS: During a median
      follow-up of 1.9 years (interquartile range: 1.3 to 2.7 years), 660 (2.9%)
      patients had a stroke. These patients were older, more often female, smokers, and
      hypertensive; they had a higher Killip class; a lower estimated glomerular
      filtration rate; and a higher proportion of MI, HF, diabetes, and stroke
      histories. The final stroke risk model retained older age, Killip class 3 or 4,
      estimated glomerular filtration rate <=45 ml/min/1.73 m2, hypertension history,
      and previous stroke. The models were well calibrated and showed moderate to good
      discrimination (C-index = 0.67). The observed 3-year event rates increased
      steeply for each sextile of the stroke risk score (1.8%, 2.9%, 4.1%, 5.6%, 8.3%,
      and 10.9%, respectively) and were in agreement with the expected event rates.
      CONCLUSIONS: Readily accessible risk factors associated with the occurrence of
      stroke were identified and incorporated in an easy-to-use risk score. This score
      may help in the identification of patients with MI and HF and a high risk for
      stroke despite their not presenting with AF.

PMID- 29447734
TI  - Risk Scores-Medical Derivatives.

PMID- 29447736
TI  - Long-Term Outcomes of Post-Operative Atrial Fibrillation: Guilty as Charged.

PMID- 29447735
TI  - New-Onset Atrial Fibrillation After PCI or CABG for Left Main Disease: The EXCEL
      Trial.
AB  - BACKGROUND: There is limited information on the incidence and prognostic impact
      of new-onset atrial fibrillation (NOAF) following percutaneous coronary
      intervention (PCI) and coronary artery bypass grafting (CABG) for left main
      coronary artery disease (LMCAD). OBJECTIVES: This study sought to determine the
      incidence of NOAF following PCI and CABG for LMCAD and its effect on 3-year
      cardiovascular outcomes. METHODS: In the EXCEL (Evaluation of XIENCE Versus
      Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization)
      trial, 1,905 patients with LMCAD and low or intermediate SYNTAX scores were
      randomized to PCI with everolimus-eluting stents versus CABG. Outcomes were
      analyzed according to the development of NOAF during the initial hospitalization
      following revascularization. RESULTS: Among 1,812 patients without atrial
      fibrillation on presentation, NOAF developed at a mean of 2.7 +/- 2.5 days after
      revascularization in 162 patients (8.9%), including 161 of 893 (18.0%) CABG
      treated patients and 1 of 919 (0.1%) PCI-treated patients (p < 0.0001). Older
      age, greater body mass index, and reduced left ventricular ejection fraction were
      independent predictors of NOAF in patients undergoing CABG. Patients with versus
      without NOAF had a significantly longer duration of hospitalization, were more
      likely to be discharged on anticoagulant therapy, and had an increased 30-day
      rate of Thrombolysis In Myocardial Infarction major or minor bleeding (14.2% vs.
      5.5%; p < 0.0001). By multivariable analysis, NOAF after CABG was an independent
      predictor of 3-year stroke (6.6% vs. 2.4%; adjusted hazard ratio [HR]: 4.19; 95%
      confidence interval [CI]: 1.74 to 10.11; p = 0.001), death (11.4% vs. 4.3%;
      adjusted HR: 3.02; 95% CI: 1.60 to 5.70; p = 0.0006), and the primary composite
      endpoint of death, MI, or stroke (22.6% vs. 12.8%; adjusted HR: 2.13; 95% CI:
      1.39 to 3.25; p = 0.0004). CONCLUSIONS: In patients with LMCAD undergoing
      revascularization in the EXCEL trial, NOAF was common after CABG but extremely
      rare after PCI. The development of NOAF was strongly associated with subsequent
      death and stroke in CABG-treated patients. Further studies are warranted to
      determine whether prophylactic strategies to prevent or treat atrial fibrillation
      may improve prognosis in patients with LMCAD who are undergoing CABG. (Evaluation
      of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main
      Revascularization [EXCEL]; NCT01205776).

PMID- 29447738
TI  - Surrogate Endpoints for Pulmonary Hypertension Management and Trial Design:
      Moving in the Right Direction.

PMID- 29447737
TI  - Pulmonary Arterial Hypertension-Related Morbidity Is Prognostic for Mortality.
AB  - BACKGROUND: Registry data suggest that disease progression in pulmonary arterial
      hypertension (PAH) is indicative of poor prognosis. However, the prognostic
      relevance of PAH-related morbidity has not been formally evaluated in randomized
      controlled trials. OBJECTIVES: The purpose of these analyses was to assess the
      impact of morbidity events on the risk of subsequent mortality using the landmark
      method and data from the SERAPHIN and GRIPHON studies. METHODS: For each study,
      the risk of all-cause death up to the end of the study was assessed from the
      landmark time point (months 3, 6, and 12) according to whether a patient had
      experienced a primary endpoint morbidity event before the landmark. Each analysis
      was conducted using data from all patients who were available for survival follow
      up at the landmark. RESULTS: In the SERAPHIN study, on the basis of the 3-month
      landmark time point, patients who experienced a morbidity event before month 3
      had an increased risk of death compared with patients who did not (hazard ratio
      [HR]: 3.39; 95% confidence interval [CI]: 1.94 to 5.92). In the GRIPHON study, on
      the basis of the 3-month landmark time point, there was also an increased risk
      with a HR of 4.48; (95% CI: 2.98 to 6.73). Analyses based on 6-month and 12-month
      landmarks also showed increased risk in patients who experienced morbidity
      events, albeit with a reduced HR. CONCLUSIONS: These results demonstrate the
      prognostic relevance of PAH-related morbidity as defined in the SERAPHIN and
      GRIPHON studies, highlighting the importance of preventing disease progression in
      patients with PAH and supporting the clinical relevance of SERAPHIN and GRIPHON
      morbidity events. (Study of Macitentan [ACT-064992] on Morbidity and Mortality in
      Patients With Symptomatic Pulmonary Arterial Hypertension [SERAPHIN];
      NCT00660179; Selexipag [ACT-293987] in Pulmonary Arterial Hypertension [GRIPHON];
      NCT01106014).

PMID- 29447740
TI  - T1 Mapping of the Remote Myocardium: When Normal Is Not Normal.

PMID- 29447739
TI  - Native T1 and ECV of Noninfarcted Myocardium and Outcome in Patients With
      Coronary Artery Disease.
AB  - BACKGROUND: Coronary artery disease (CAD) remains the major cause of cardiac
      morbidity and mortality worldwide, despite the advances in treatment with
      coronary revascularization and modern antiremodeling therapy. Risk stratification
      in CAD patients is primarily based on left ventricular volumes, ejection fraction
      (LVEF), risk scores, and the presence and extent of late gadolinium enhancement
      (LGE). The prognostic role of T1 mapping in noninfarcted myocardium in CAD
      patients has not yet been determined. OBJECTIVES: This study sought to examine
      prognostic significance of native T1 mapping of noninfarcted myocardium in
      patients with CAD. METHODS: A prospective, observational, multicenter
      longitudinal study of consecutive patients undergoing routine cardiac magnetic
      resonance imaging with T1 mapping and LGE. The primary endpoint was all-cause
      mortality. Major adverse cardiocerebrovascular events (MACCE) (cardiac mortality,
      nonfatal acute coronary syndrome, stroke, and appropriate device discharge) are
      also reported. RESULTS: A total of 34 deaths and 71 MACCE (n = 665, males n =
      424, median age [interquartile range] 57 [22] years; 64%; median follow-up period
      of 17 [11] months) were observed. Native T1 and extracellular volume were
      univariate predictors of outcome. Native T1 and LGE were stronger predictors of
      survival and MACCE compared with extracellular volume, LVEF, cardiac volumes, and
      clinical scores (p < 0.001). Native T1 of noninfarcted myocardium was the sole
      independent predictor of all-cause mortality (chi-square = 21.7; p < 0.001),
      which was accentuated in the absence of LGE or LVEF <=35%. For MACCE, native T1
      and LGE extent were joint independent predictors (chi-square = 25.6; p < 0.001).
      CONCLUSIONS: Characterization of noninfarcted myocardium by native T1 is an
      important predictor of outcome in CAD patients, over and above the traditional
      risk stratifiers. The current study's results provide a basis for a novel risk
      stratification model in CAD based on a complementary assessment of noninfarcted
      myocardium and post-infarction scar, by native T1 mapping and LGE, respectively.

PMID- 29447741
TI  - The Burden of Iron Deficiency in Heart Failure: Therapeutic Approach.
AB  - Heart failure (HF) is highlighted by its burdening symptom-limited exercise
      capacity and recurrent hospitalizations. Despite substantial advances regarding
      disease-modifying drugs in HF with reduced ejection fraction, additional
      therapeutic strategies to improve quality of life are invaluable. Currently, iron
      deficiency (ID) is overwhelmingly recognized in over 30% to 50% of patients with
      stable chronic HF, which worsens prognosis. The established pathophysiological
      mechanisms of progressive HF may be intertwined with increasing myocardial iron
      scarcity, wherein one begets the other. Most importantly, ID constitutes a novel
      target for symptom relief in carefully selected patients. In this regard,
      intravenous iron may be a safe and efficacious intervention, potentially reducing
      HF hospitalizations. We discuss the evidence and gaps in knowledge concerning
      iron therapy in HF and propose a practical, comprehensive, clinically oriented
      algorithm for timely adequate iron replenishment in different clinical scenarios.
      Finally, we further debate imperative decision-making before intervention and the
      drawbacks of such a strategy.

PMID- 29447742
TI  - A Comparative Analysis of Current Lipid Treatment Guidelines: Nothing Stands
      Still.
AB  - Lipid treatment guidelines have continued to evolve as new evidence emerges. We
      sought to review similarities and differences of 5 lipid treatment guidelines
      from the American College of Cardiology/American Heart Association, Canadian
      Cardiovascular Society, European Society for Cardiology/European Atherosclerosis
      Society, U.S. Preventive Services Task Force, and U.S. Veterans
      Affairs/Department of Defense. All guidelines utilize rigorous evidentiary
      review, highlight statin therapy for primary and secondary prevention of
      atherosclerotic cardiovascular disease, and emphasize a clinician-patient risk
      discussion. However, there are differences in statin intensities, use of risk
      estimators, treatment of specific patient subgroups, and consideration of safety
      concerns. Clinicians should understand these similarities and differences in
      current and future guideline recommendations when considering if and how to treat
      their patients with statin therapy.

PMID- 29447743
TI  - A Hybrid Model for Advanced Structural Heart Disease Training Programs: The
      Attending-Fellow-in-Training Model.

PMID- 29447744
TI  - Awareness of Heart Attack Signs and Symptoms and Calling 9-1-1 Among U.S. Adults.

PMID- 29447745
TI  - Takotsubo Syndrome Associated With Structural Brain Alterations of the Limbic
      System.

PMID- 29447746
TI  - High Proportions of Coexisting Aortic Dilations Call for Total Aortic Scan.

PMID- 29447747
TI  - Impact of Physical Activity and Fitness in Metabolically Healthy Obesity.

PMID- 29447748
TI  - Metabolically Healthy Obese and Cardiovascular Diseases: A Phenotype
      Misunderstanding.

PMID- 29447749
TI  - Plasma Sphingolipidome as a Surrogate for Human Metabolic Heath.

PMID- 29447750
TI  - Preventive Health Care Should Focus on Modifiable Cardiovascular Risk Factors,
      Not Obesity Alone.

PMID- 29447751
TI  - Reply: Is Metabolically Healthy Obesity a Harmless Condition?

PMID- 29447752
TI  - RETRACTED: The revised stratigraphy of the hominin-bearing site of Kromdraai
      (Gauteng, South Africa) and associated perspectives.
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy). This article has been
      retracted at the request of the co-Editors-in-Chief and the authors. The Results
      and Discussion of this article duplicate significant parts of book chapter "A
      revised stratigraphy of Kromdraai", published by L.B., R.M., R.C., F.T. and J.B.
      in Braga, J. and Thackeray, J.F. (Eds.), "Kromdraai. A Birthplace of Paranthropus
      in the Cradle of Humankind" (2016, SUN MeDIA MeTRO, pp. 31-47),
      https://doi.org/10.18820/9781928355076. One of the conditions of submission of a
      paper to Journal of Human Evolution is that authors declare explicitly that that
      their work is original and has not been published previously. Reuse of any data
      should be appropriately cited. As such this article represents an abuse of the
      scientific publishing system. The scientific community takes a very strong view
      on this matter and apologies are offered to readers of the journal that this was
      not detected during the submission process.

PMID- 29447753
TI  - Kinematics of the anthropoid os centrale and the functional consequences of
      scaphoid-centrale fusion in African apes and hominins.
AB  - In most primates, the os centrale is interposed between the scaphoid, trapezoid,
      trapezium, and head of the capitate, thus constituting a component of the wrist's
      midcarpal complex. Scaphoid-centrale fusion is among the clearest morphological
      synapomorphies of African apes and hominins. Although it might facilitate knuckle
      walking by increasing the rigidity and stability of the radial side of the wrist,
      the exact functional significance of scaphoid-centrale fusion is unclear. If
      fusion acts to produce a more rigid radial wrist that stabilizes the hand and
      limits shearing stresses, then in taxa with a free centrale, it should anchor
      ligaments that check extension and radial deviation, but exhibit motion
      independent of the scaphoid. Moreover, because the centrale sits between the
      scaphoid and capitate (a major stabilizing articulation), scaphoid-centrale
      mobility should correlate with scaphocapitate mobility in extension and radial
      deviation. To test these hypotheses, the centrale's ligamentous binding was
      investigated via dissection in Pongo and Papio, and the kinematics of the
      centrale were quantified in a cadaveric sample of anthropoids (Pongo sp., Ateles
      geoffroyi, Colobus guereza, Macaca mulatta, and Papio anubis) using a computed
      tomography-based method to track wrist-bone motion. Results indicate that the
      centrale rotates freely relative to the scaphoid in all taxa. However, centrale
      mobility is only correlated with scaphocapitate mobility during extension in
      Pongo-possibly due to differences in overall wrist configuration between apes and
      monkeys. If an extant ape-like wrist characterized early ancestors of African
      apes and hominins, then scaphoid-centrale fusion would have increased midcarpal
      rigidity in extension relative to the primitive condition. Although
      biomechanically consistent with a knuckle-walking hominin ancestor, this assumes
      that the trait evolved specifically for that biological role, which must be
      squared with contradictory interpretations of extant and fossil hominoid
      morphology. Regardless of its original adaptive significance, scaphoid-centrale
      fusion likely presented a constraint on early hominin midcarpal mobility.

PMID- 29447754
TI  - Strontium isotopic aspects of Paranthropus robustus teeth; implications for
      habitat, residence, and growth.
AB  - The strontium isotopic ratio 87Sr/86Sr has been studied in the Sterkfontein
      Valley of South Africa to infer both habitat usage and residence for a number of
      early hominins. This paper examines the existing 87Sr/86Sr data collectively
      derived from three studies of Paranthropus robustus teeth with the aim of
      exploring whether the dataset as a whole may provide deeper insight into habitat,
      mobility, and growth for this species. 87Sr/86Sr from seven Swartkrans Member I
      third molars varies in a well defined narrow range, and while some canines were
      consistent with this range, a number of P. robustus canines and first and second
      molars were not, and therefore represent individuals who had arrived from other
      localities. A first and third molar 87Sr/86Sr was found to differ in TM1517c, the
      holotype P. robustus specimen from Kromdraai, suggesting this individual had
      moved to the locality sometime after the first molar and before the third molar
      had completely mineralized. While early forming teeth vary widely, the relatively
      low variation and absence of exogenous 87Sr/86Sr in third molars suggest that
      these teeth mineralized relatively late when compared to life history events
      bearing on higher primate residence patterns. The implications for further study
      of habitat, residence, and growth are discussed.

PMID- 29447755
TI  - Maturation is prolonged and variable in female chimpanzees.
AB  - Chimpanzees are important referential models for the study of life history in
      hominin evolution. Age at sexual maturity and first reproduction are key life
      history milestones that mark the diversion of energy from growth to reproduction
      and are essential in comparing life history trajectories between chimpanzees and
      humans. Yet, accurate information on ages at these milestones in wild chimpanzees
      is difficult to obtain because most females transfer before breeding. Precise age
      at first birth is only known from a relatively small number of non-dispersing
      individuals. Moreover, due to small sample sizes, the degree to which age at
      maturation milestones varies is unknown. Here we report maturation milestones and
      explore sources of variance for 36 wild female chimpanzees of known age,
      including eight dispersing females born in Gombe National Park, Tanzania. Using
      Kaplan-Meier survival analysis, including censored intervals, we find an average
      age of 11.5 years (range 8.5-13.9) at sexual maturity and 14.9 years (range 11.1
      22.1) at first birth. These values exceed previously published averages for wild
      chimpanzees by one or more years. Even in this larger sample, age at first birth
      is likely underestimated due to the disproportionate number of non-dispersing
      females, which, on average, give birth two years earlier than dispersing females.
      Model selection using Cox Proportional Hazards models shows that age at sexual
      maturity is delayed in females orphaned before age eight years and those born to
      low-ranking mothers. Age at first birth is most delayed in dispersing females and
      those orphaned before age eight years. These data provide improved estimates of
      maturation milestones in a population of wild female chimpanzees and indicate the
      importance of maternal factors in development.

PMID- 29447756
TI  - The biomechanical significance of the frontal sinus in Kabwe 1 (Homo
      heidelbergensis).
AB  - Paranasal sinuses are highly variable among living and fossil hominins and their
      function(s) are poorly understood. It has been argued they serve no particular
      function and are biological 'spandrels' arising as a structural consequence of
      changes in associated bones and/or soft tissue structures. In contrast, others
      have suggested that sinuses have one or more functions, in olfaction,
      respiration, thermoregulation, nitric oxide production, voice resonance,
      reduction of skull weight, and craniofacial biomechanics. Here we assess the
      extent to which the very large frontal sinus of Kabwe 1 impacts on the mechanical
      performance of the craniofacial skeleton during biting. It may be that the
      browridge is large and the sinus has large trabecular struts traversing it to
      compensate for the effect of a large sinus on the ability of the face to resist
      forces arising from biting. Alternatively, the large sinus may have no impact and
      be sited where strains that arise from biting would be very low. If the former is
      true, then infilling of the sinus would be expected to increase the ability of
      the skeleton to resist biting loads, while removing the struts might have the
      opposite effect. To these ends, finite element models with hollowed and infilled
      variants of the original sinus were created and loaded to simulate different
      bites. The deformations arising due to loading were then compared among different
      models and bites by contrasting the strain vectors arising during identical
      biting tasks. It was found that the frontal bone experiences very low strains and
      that infilling or hollowing of the sinus has little effect on strains over the
      cranial surface, with small effects over the frontal bone. The material used to
      infill the sinus experienced very low strains. This is consistent with the idea
      that frontal sinus morphogenesis is influenced by the strain field experienced by
      this region such that it comes to lie entirely within a region of the cranium
      that would otherwise experience low strains. This has implications for
      understanding why sinuses vary among hominin fossils.

PMID- 29447757
TI  - Using the covariation of extant hominoid upper and lower jaws to predict dental
      arcades of extinct hominins.
AB  - Upper and lower jaws are well represented in the fossil record of mammals and are
      frequently used to diagnose species. Some hominin species are only known by
      either their maxillary or mandibular morphology, and in this study, we explore
      the possibility of predicting their complementary dental arcade shape to aid the
      recognition of conspecific specimens in the fossil record. To this end, we apply
      multiple multivariate regression to analyze 3D landmark coordinates collected on
      associated upper and lower dental arcades of extant Homo, Pan, Gorilla, Pongo,
      and Hylobates. We first study the extant patterns of variation in dental arcade
      shape and quantify how accurate predictions of complementary arcades are. Then we
      explore applications of this extant framework for interpreting the fossil record
      based on two fossil hominin specimens with associated upper and lower jaws, KNM
      WT 15000 (Homo erectus sensu lato) and Sts 52 (Australopithecus africanus), as
      well as two non-associated specimens of Paranthropus boisei, the maxilla of OH 5
      and the Peninj mandible. We find that the shape differences between the
      predictions and the original fossil specimens are in the range of variation
      within genera or species and therefore are consistent with their known affinity.
      Our approach can provide a reference against which intraspecific variation of
      extinct species can be assessed. We show that our method predicts arcade shapes
      reliably even if the target shape is not represented in the reference sample. We
      find that in extant hominoids, the amount of within-taxon variation in dental
      arcade shape often overlaps with the amount of between-taxon shape variation.
      This implies that whereas a large difference in dental arcade shape between two
      individuals typically suggests that they belong to different species or even
      genera, a small shape difference does not necessarily imply conspecificity.

PMID- 29447758
TI  - Nasolacrimal anatomy and haplorhine origins.
AB  - Computed tomography X-ray imaging of the internal face in well-preserved primate
      fossil crania permits reconstruction of the nature of their nasal anatomy,
      including some soft-tissue features. These features are diagnostic of the primate
      suborder Haplorhini, and allow reevaluation of the phylogenetic status of several
      purported early members of the group. Here we examine the nasolacrimal morphology
      of a broad sample of extant primates, as well as a number of Paleogene fossils.
      The extant sample confirms the distinctiveness of the two suborders. Of the
      fossils studied, only Shoshonius cooperi from the late-early Eocene exhibits
      evidence of a haplorhine nose. This suggests that the haplorhine oronasal complex
      may have evolved before the postorbital septum, and strengthens the claim that
      Shoshonius is a close relative of tarsiers and anthropoids. These results
      indicate that Omomyiformes is not a monophyletic group, and that few of its
      members possessed the derived oronasal morphology that characterizes crown
      haplorhines.

PMID- 29447759
TI  - Ecomorphological analysis of bovid mandibles from Laetoli Tanzania using 3D
      geometric morphometrics: Implications for hominin paleoenvironmental
      reconstruction.
AB  - The current study describes a new method of mandibular ecological morphology
      (ecomorphology). Three-dimensional geometric morphometrics (3D GM) was used to
      quantify mandibular shape variation between extant bovids with different feeding
      preferences. Landmark data were subjected to generalized Procrustes analysis
      (GPA), principal components analysis (PCA), and discriminant function analysis
      (DFA). The PCA resulted in a continuum from grazers to browsers along PC1 and DFA
      classified 88% or more of the modern specimens to the correct feeding category.
      The protocol was reduced to a subset of landmarks on the mandibular corpus in
      order to make it applicable to incomplete fossils. The reduced landmark set
      resulted in greater overlap between feeding categories but maintained the same
      continuum as the complete landmark model. The DFA resubstitution and jackknife
      analyses resulted in classification success rates of 85% and 80%, respectively.
      The reduced landmark model was applied to fossil mandibles from the Upper
      Laetolil Beds (~4.3-3.5 Ma) and Upper Ndolanya Beds (~2.7-2.6 Ma) at Laetoli,
      Tanzania in order to assess antelope diet, and indirectly evaluate paleo
      vegetation structure. The majority of the fossils were classified by the DFA as
      browsers or mixed feeders preferring browse. Our results indicate a continuous
      presence of wooded habitats and are congruent with recent environmental studies
      at Laetoli indicating a mosaic woodland-bushland-grassland savanna ecosystem.

PMID- 29447760
TI  - Climatic controls on Later Stone Age human adaptation in Africa's southern Cape.
AB  - Africa's southern Cape is a key region for the evolution of our species, with
      early symbolic systems, marine faunal exploitation, and episodic production of
      microlithic stone tools taken as evidence for the appearance of distinctively
      complex human behavior. However, the temporally discontinuous nature of this
      evidence precludes ready assumptions of intrinsic adaptive benefit, and has
      encouraged diverse explanations for the occurrence of these behaviors, in terms
      of regional demographic, social and ecological conditions. Here, we present a new
      high-resolution multi-proxy record of environmental change that indicates that
      faunal exploitation patterns and lithic technologies track climatic variation
      across the last 22,300 years in the southern Cape. Conditions during the Last
      Glacial Maximum and deglaciation were humid, and zooarchaeological data indicate
      high foraging returns. By contrast, the Holocene is characterized by much drier
      conditions and a degraded resource base. Critically, we demonstrate that systems
      for technological delivery - or provisioning - were responsive to changing
      humidity and environmental productivity. However, in contrast to prevailing
      models, bladelet-rich microlithic technologies were deployed under conditions of
      high foraging returns and abandoned in response to increased aridity and less
      productive subsistence environments. This suggests that posited links between
      microlithic technologies and subsistence risk are not universal, and the
      behavioral sophistication of human populations is reflected in their adaptive
      flexibility rather than in the use of specific technological systems.

PMID- 29447761
TI  - New Neandertal wrist bones from El Sidron, Spain (1994-2009).
AB  - Twenty-nine carpal bones of Homo neanderthalensis have been recovered from the
      site of El Sidron (Asturias, Spain) during excavations between 1994 and 2009,
      alongside ~2500 other Neandertal skeletal elements dated to ~49,000 years ago.
      All bones of the wrist are represented, including adult scaphoids (n = 6),
      lunates (n = 2), triquetra (n = 4), pisiforms (n = 2), trapezia (n = 2),
      trapezoids (n = 5), capitates (n = 5), and hamates (n = 2), as well as one
      fragmentary and possibly juvenile scaphoid. Several of these carpals appear to
      belong to the complete right wrist of a single individual. Here we provide
      qualitative and quantitative morphological descriptions of these carpals, within
      a comparative context of other European and Near Eastern Neandertals, early and
      recent Homo sapiens, and other fossil hominins, including Homo antecessor, Homo
      naledi, and australopiths. Overall, the El Sidron carpals show characteristics
      that typically distinguish Neandertals from H. sapiens, such as a relatively flat
      first metacarpal facet on the trapezium and a more laterally oriented second
      metacarpal facet on the capitate. However, there are some distinctive features of
      the El Sidron carpals compared with most other Neandertals. For example, the
      tubercle of the trapezium is small with limited projection, while the scaphoid
      tubercle and hamate hamulus are among the largest seen in other Neandertals.
      Furthermore, three of the six adult scaphoids show a distinctive os-centrale
      portion, while another is a bipartite scaphoid with a truncated tubercle. The
      high frequency of rare carpal morphologies supports other evidence of a close
      genetic relationship among the Neandertals found at El Sidron.

PMID- 29447762
TI  - The easternmost Middle Paleolithic (Mousterian) from Jinsitai Cave, North China.
AB  - The dispersal of Neanderthals and their genetic and cultural interactions with
      anatomically modern humans and other hominin populations in Eurasia are critical
      issues in human evolution research. Neither Neanderthal fossils nor typical
      Mousterian assemblages have been reported in East Asia to date. Here we report on
      artifact assemblages comparable to western Eurasian Middle Paleolithic
      (Mousterian) at Jinsitai, a cave site in North China. The lithic industry at
      Jinsitai appeared at least 47-42 ka and persisted until around 40-37 ka. These
      findings expand the geographic range of the Mousterian-like industries at least
      2000 km further to the east than what has been previously recognized. This
      discovery supplies a missing part of the picture of Middle Paleolithic
      distribution in Eurasia and also demonstrates the makers' capacity to adapt to
      diverse geographic regions and habitats of Eurasia.

PMID- 29447763
TI  - Scaling of bony canals for encephalic vessels in euarchontans: Implications for
      the role of the vertebral artery and brain metabolism.
AB  - Supplying the central nervous system with oxygen and glucose for metabolic
      activities is a critical function for all animals at physiologic, anatomical, and
      behavioral levels. A relatively proximate challenge to nourishing the brain is
      maintaining adequate blood flow. Euarchontans (primates, dermopterans and
      treeshrews) display a diversity of solutions to this challenge. Although the
      vertebral artery is a major encephalic vessel, previous research has questioned
      its importance for irrigating the cerebrum. This presents a puzzling scenario for
      certain strepsirrhine primates (non-cheirogaleid lemuriforms) that have reduced
      promontorial branches of the internal carotid artery and no apparent alternative
      encephalic vascular route except for the vertebral artery. Here, we present
      results of phylogenetic comparative analyses of data on the cross-sectional area
      of bony canals that transmit the vertebral artery (transverse foramina). These
      results show that, across primates (and within major primate subgroups),
      variation in the transverse foramina helps significantly to explain variation in
      forebrain mass even when variation in promontorial canal cross-sectional areas
      are also considered. Furthermore, non-cheirogaleid lemuriforms have larger
      transverse foramina for their endocranial volume than other euarchontans,
      suggesting that the vertebral arteries compensate for reduced promontorial artery
      size. We also find that, among internal carotid-reliant euarchontans, species
      that are more encephalized tend to have a promontorial canal that is larger
      relative to the transverse foramina. Tentatively, we consider the correlation
      between arterial canal diameters (as a proxy for blood flow) and brain metabolic
      demands. The results of this analysis imply that human investment in brain
      metabolism (~27% of basal metabolic rate) may not be exceptional among
      euarchontans.

PMID- 29447764
TI  - Retraction notice to: The revised stratigraphy of the hominin-bearing site of
      Kromdraai (Gauteng, South Africa) and associated perspectives [J. Human Evol. 114
      (2018) 1-19].

PMID- 29447765
TI  - Movement disorders in children: The need to observe, describe in detail and
      integrate your findings to the global clinical picture.

PMID- 29447766
TI  - Dystonia in childhood: Rising networks.

PMID- 29447767
TI  - Deep brain stimulation in cerebral palsy: Time for dynamism in a static
      encephalopathy.

PMID- 29447768
TI  - Childhood Acute Neuropsychiatric Syndromes...furthering the discussion PANS and
      PANDAS.

PMID- 29447769
TI  - Apixaban following acute coronary syndromes in patients with prior stroke:
      Insights from the APPRAISE-2 trial.
AB  - BACKGROUND AND PURPOSE: Patients with prior stroke are at greater risk for
      recurrent cardiovascular events post-acute coronary syndromes (ACS) and may have
      a different risk/benefit profile with antithrombotic therapy than patients
      without prior stroke. METHODS: We studied 7391 patients with ACS from APPRAISE-2,
      stratified by the presence or absence of prior stroke. Baseline characteristics
      and outcomes of cardiovascular death, myocardial infarction (MI), or stroke were
      compared between groups. Interactions between prior stroke, treatment assignment
      (apixaban vs placebo), and outcomes were tested before and after multivariable
      adjustment with Cox proportional hazards models. RESULTS: A total of 902 patients
      (12%) had prior stroke. Those with prior stroke were older (69 vs 67 years), had
      more hypertension (91% vs 77%), peripheral vascular disease (22% vs18%), and
      impaired renal function (38% vs 30%) but less diabetes (44% vs 48%) than those
      without prior stroke. Patients with prior stroke vs no prior stroke had higher
      unadjusted rates of cardiovascular death (4.8% vs 4.0%), MI (11.2% vs 7.1%), and
      ischemic stroke (3.2% vs 0.9%). Patients with prior stroke assigned to apixaban
      had similar rates of the composite of cardiovascular death, MI, or stroke
      compared with those assigned to placebo (HR 1.39; 95% CI 0.92-2.08). Patients
      without prior stroke assigned to apixaban had similar rates of cardiovascular
      death, MI, or ischemic stroke compared with those assigned to placebo (HR 0.87;
      95% CI 0.73-1.04; P-interaction=.041). Median follow-up was 240 days.
      CONCLUSIONS: Patients with prior stroke are at higher risk for recurrent
      cardiovascular events post-ACS and had a differential risk/benefit profile with
      oral anticoagulation.

PMID- 29447770
TI  - Efficacy and safety of dual antiplatelet therapy after coronary stenting in
      patients with chronic kidney disease.
AB  - BACKGROUND: We compared efficacy and safety of short- (3 or 6 months) versus long
      term (>=12 months) dual antiplatelet therapy (DAPT) after drug-eluting stent
      (DES) implantation, according to the presence of chronic kidney disease (CKD).
      METHODS: Patient-level pooled analysis was performed with 7242 patients (87.2%
      with 2nd generation DES) from 5 randomized controlled trials. RESULTS: In both
      CKD (1273 patients) and non-CKD (5969 patients) population, the rates of patient
      oriented composite outcomes at 1-year (POCO, all-cause death, any myocardial
      infarction [MI], stroke and TIMI major bleeding) were not different between the
      short- and long-term DAPT (hazard ratio [HR] 1.19, 95% confidence interval [CI]
      0.76-1.86, P=.449 in CKD population; HR 1.14, 95% CI 0.83-1.56, P=.434 in non-CKD
      population). The rates of coronary thrombotic events (any MI and
      definite/probable stent thrombosis) also did not differ between short- and long
      term DAPT in either CKD or non-CKD population. As for bleeding events, long-term
      DAPT increased the TIMI major bleeding (HR 2.91, 95% CI 1.31-6.48, P=.009) in non
      CKD population. The similar trend was observed with long-term DAPT in CKD
      population. But it did not reach statistical significance (HR 3.15, 95% CI 0.64
      15.63, P=.160). CONCLUSIONS: The rates of POCO and coronary thrombotic events
      were significantly higher in patients with CKD compared with those without CKD,
      which were not affected by short- or long-term DAPT. Higher bleeding incidence by
      long-term DAPT was only observed in non-CKD patients but not in CKD patients.
      Further large scale studies are warranted to confirm our findings.

PMID- 29447771
TI  - Topographical distribution of perioperative cerebral infarction associated with
      transcatheter aortic valve implantation.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is associated with a
      high incidence of cerebrovascular injury. As these injuries are thought to be
      primarily embolic, neuroprotection strategies have focused on embolic protection
      devices. However, the topographical distribution of cerebral emboli and how this
      impacts on the effectiveness of these devices have not been thoroughly assessed.
      Here, we evaluated the anatomical characteristics of magnetic resonance imaging
      (MRI)-defined cerebral ischemic lesions occurring secondary to TAVI to enhance
      our understanding of the distribution of cardioembolic phenomena. METHODS: Forty
      patients undergoing transfemoral TAVI with an Edwards SAPIEN-XT valve under
      general anesthesia were enrolled prospectively in this observational study.
      Participants underwent brain MRI preprocedure, and 3 +/- 1 days and 6 +/- 1
      months postprocedure. RESULTS: Mean +/- SD participant age was 82 +/- 7 years.
      Patients had an intermediate to high surgical risk, with a mean Society of
      Thoracic Surgeons score of 6.3 +/- 3.5 and EuroSCORE of 18.1 +/- 10.6. Post-TAVI,
      there were no clinically apparent cerebrovascular events, but MRI assessments
      identified 83 new lesions across 19 of 31 (61%) participants, with a median +/-
      interquartile range number and volume of 1 +/- 2.8 lesions and 20 +/- 190 MUL per
      patient. By volume, 80% of the infarcts were cortical, 90% in the posterior
      circulation and 81% in the right hemisphere. CONCLUSIONS: The distribution of
      lesions that we detected suggests that cortical gray matter, the posterior
      circulation, and the right hemisphere are all particularly vulnerable to
      perioperative cerebrovascular injury. This finding has implications for the use
      of intraoperative cerebral embolic protection devices, particularly those that
      leave the left subclavian and, therefore, left vertebral artery unprotected.

PMID- 29447772
TI  - The Optimal Anti-Coagulation for Enhanced-Risk Patients Post-Catheter Ablation
      for Atrial Fibrillation (OCEAN) trial.
AB  - BACKGROUND: The optimal long-term antithrombotic regimen for patients after
      successful catheter-based atrial fibrillation (AF) ablation is not well defined.
      Presently, practice variation exists, and the benefits of oral anticoagulation
      over antiplatelet therapy across the entire spectrum of stroke risk profile
      remain undefined in the postablation population. To date, there are no randomized
      trials to inform clinicians on this therapeutic question. OBJECTIVE: The
      objective was to assess whether rivaroxaban is superior to acetylsalicylic acid
      (ASA) in reducing the risk of clinically overt stroke, systemic embolism, or
      covert stroke among patients without apparent recurrent atrial arrhythmias for at
      least 1 year after their most recent AF ablation procedure. METHODS/DESIGN: A
      prospective, multicenter, open-label, randomized trial with blinded assessment of
      outcomes is under way (NCT02168829). Atrial fibrillation patients with at least 1
      stroke risk factor (as defined by the CHA2DS2-VASc score) and without known
      atrial arrhythmia recurrences for at least 12 months after ablation are
      randomized to rivaroxaban 15 mg or ASA 75-160 mg daily. The primary outcome is a
      composite of clinically overt stroke, systemic embolism, and covert stroke based
      on brain magnetic resonance imaging. Key secondary outcomes include major
      bleeding outcomes, intracranial hemorrhage, transient ischemic attack,
      neuropsychological testing, quality of life, and an economic analysis. Subjects
      will be followed for 3 years. The estimated overall sample size is 1,572 subjects
      (786 per arm). DISCUSSION: The OCEAN trial is a multicenter randomized controlled
      trial evaluating 2 antithrombotic treatment strategies for patients with risk
      factors for stroke after apparently successful AF ablation. We hypothesize that
      rivaroxaban will reduce the occurrence of clinically overt stroke, systemic
      embolism, and covert stroke when compared with ASA alone.

PMID- 29447773
TI  - Percutaneous coronary intervention and antiplatelet therapy in patients with
      atrial fibrillation receiving apixaban or warfarin: Insights from the ARISTOTLE
      trial.
AB  - BACKGROUND: We assessed antiplatelet therapy use and outcomes in patients
      undergoing percutaneous coronary intervention (PCI) during the ARISTOTLE trial.
      METHODS: Patients were categorized based on the occurrence of PCI during follow
      up (median 1.8 years); PCI details and outcomes post-PCI are reported. Of the
      18,201 trial participants, 316 (1.7%) underwent PCI (152 in apixaban group, 164
      in warfarin group). RESULTS: At the time of PCI, 84% (267) were on study drug
      (either apixaban or warfarin). Of these, 19% did not stop study drug during PCI,
      49% stopped and restarted <5 days post-PCI, and 30% stopped and restarted >5 days
      post-PCI. At 30 days post-PCI, 35% of patients received dual -antiplatelet
      therapy (DAPT), 23% received aspirin only, and 13% received a P2Y12 inhibitor
      only; 29% received no antiplatelet therapy. Triple therapy (DAPT + oral
      anticoagulant [OAC]) was used in 21% of patients, 23% received OAC only, 15%
      received OAC plus aspirin, and 9% received OAC plus a P2Y12 inhibitor; 32%
      received antiplatelet agents without OAC. Post-PCI, patients assigned to apixaban
      versus warfarin had numerically similar rates of major bleeding (5.93 vs 6.73
      events/100 patient-years; P = .95) and stroke (2.74 vs 1.84 events/100 patient
      years; P = .62). CONCLUSIONS: PCI occurred infrequently during follow-up. Most
      patients on study drug at the time of PCI remained on study drug in the peri-PCI
      period; 19% continued the study drug without interruption. Antiplatelet therapy
      use post-PCI was variable, although most patients received DAPT. Additional data
      are needed to guide the use of antithrombotics in patients undergoing PCI.

PMID- 29447774
TI  - Percutaneous coronary intervention of lesions with in-stent restenosis: A report
      from the ADAPT-DES study.
AB  - BACKGROUND: There is a paucity of data from large contemporary cohorts of
      patients with in-stent restenosis (ISR) treated with drug-eluting stents (DESs),
      and no studies have examined the impact of high platelet reactivity (HPR) on the
      occurrence of ischemic events after ISR percutaneous coronary intervention (PCI)
      with DESs. We sought to report outcomes after PCI of ISR lesions and its
      association with HPR. METHODS: Patients in the prospective, multicenter ADAPT-DES
      study were stratified according to whether they had ISR versus non-ISR PCI. Two
      year outcomes were compared between the groups using Cox proportional hazards
      models. HPR was defined as on-clopidogrel P2Y12 platelet reaction units >208 as
      measured by the VerifyNow assay; target vessel failure (TVF) was defined as the
      composite of all-cause death, myocardial infarction, or ischemia-driven target
      vessel revascularization. RESULTS: Among the 8,582 patients included in the ADAPT
      DES study, 840 (9.8%) patients underwent successful ISR PCI. ISR PCI was
      independently associated with a higher 2-year risk of TVF (adjusted hazard ratio
      [HR] 1.95; 95% CI 1.68-2.27; P<.001) and stent thrombosis (adjusted HR 1.95; 95%
      CI 1.08-3.51; P=.027) but not bleeding (adjusted HR 0.94; 95% CI 0.73-1.21;
      P=.64). There was no statistical interaction between HPR and ISR versus non-ISR
      PCI in regard to TVF (adjusted Pinteraction=.81). CONCLUSIONS: ISR PCI is
      associated with a considerably higher risk of 2-year adverse ischemic events,
      with HPR conferring similar risk in ISR and non-ISR PCI. More effective
      therapeutic strategies for managing ISR lesions are necessary.

PMID- 29447775
TI  - A population health perspective on a claims and electronic health record-based
      tool to screen for suboptimal medication adherence.

PMID- 29447777
TI  - Cognition and brain changes associated with high-dose atorvastatin: A BOLD
      proposition?

PMID- 29447776
TI  - The relative benefits of claims and electronic health record data for predicting
      medication adherence trajectory.
AB  - BACKGROUND: Healthcare providers are increasingly encouraged to improve their
      patients' adherence to chronic disease medications. Prediction of adherence can
      identify patients in need of intervention, but most prediction efforts have
      focused on claims data, which may be unavailable to providers. Electronic health
      records (EHR) are readily available and may provide richer information with which
      to predict adherence than is currently available through claims. METHODS: In a
      linked database of complete Medicare Advantage claims and comprehensive EHR from
      a multi-specialty outpatient practice, we identified patients who filled a
      prescription for a statin, antihypertensive, or oral antidiabetic during 2011 to
      2012. We followed patients to identify subsequent medication filling patterns and
      used group-based trajectory models to assign patients to adherence trajectories.
      We then identified potential predictors from both claims and EHR data and fit a
      series of models to evaluate the accuracy of each data source in predicting
      medication adherence. RESULTS: Claims were highly predictive of patients in the
      worst adherence trajectory (C=0.78), but EHR data also provided good predictions
      (C=0.72). Among claims predictors, presence of a prior gap in filling of at least
      6 days was by far the most influential predictor. In contrast, good predictions
      from EHR data required complex models with many variables. CONCLUSION: EHR data
      can provide good predictions of adherence trajectory and therefore may be useful
      for providers seeking to deploy resource-intensive interventions. However, prior
      adherence information derived from claims is most predictive, and can supplement
      EHR data when it is available.

PMID- 29447779
TI  - Changes in lipoprotein(a) following bariatric surgery.

PMID- 29447778
TI  - The effect of high-dose atorvastatin on neural activity and cognitive function.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) has not been used to
      assess the effects of statins on the brain. We assessed the effect of statins on
      cognition using standard neuropsychological assessments and brain neural
      activation with fMRI on two tasks. METHODS: Healthy statin-naive men and women
      (48+/-15 years) were randomized to 80 mg/day atorvastatin (n=66; 27 men) or
      placebo (n=84; 48 men) for 6 months. Participants completed cognitive testing
      while on study drug and 2 months after treatment cessation using alternative test
      and task versions. RESULTS: There were few changes in standard neuropsychological
      tests with drug treatment (all P>.56). Total and delayed recall from the Hopkins
      Verbal Learning Test-Revised increased in both groups (P<.05). The Stroop Color
      Word score increased (P<.01) and the 18-Point Clock Test decreased in the placebo
      group (P=.02) after drug cessation. There were, however, small but significant
      group-time interactions for each fMRI task: participants on placebo had greater
      activation in the right putamen/dorsal striatum during the maintenance phase of
      the Sternberg task while on placebo but the effect was reversed after drug
      washout (P<.001). Participants on atorvastatin had greater activation in the
      bilateral precuneus during the encoding phase of the Figural Memory task while on
      drug but the effect was reversed after drug washout (P<.001). CONCLUSION: Six
      months of high dose atorvastatin therapy is not associated with measurable
      changes in neuropsychological test scores, but did evoke transient differences in
      brain activation patterns. Larger, longer-term clinical trials are necessary to
      confirm these findings and evaluate their clinical implications.

PMID- 29447780
TI  - Nonprimary PCI at hospitals without cardiac surgery on-site: Consistent outcomes
      for all?
AB  - BACKGROUND: The CPORT-E trial showed the noninferiority of nonprimary
      percutaneous coronary intervention (PCI) at hospitals without cardiac surgery on
      site (SoS) compared with hospitals with SoS for 6-week mortality and 9-month
      major adverse cardiac events (MACE). However, target vessel revascularization
      (TVR) was increased at non-SoS hospitals. Therefore, we aimed to determine the
      consistency of the CPORT-E trial findings across the spectrum of enrolled
      patients. METHODS: Post hoc subgroup analyses of 6-week mortality and 9-month
      MACE, defined as the composite of death, Q-wave myocardial infarction, or TVR,
      were performed. Patients with and without 9-month TVR and rates of related
      outcomes were compared. RESULTS: There was no interaction between SoS status and
      clinically relevant subgroups for 6-week mortality or 9-month MACE (P for any
      interaction=.421 and .062, respectively). In addition to increased 9-month rates
      of TVR and diagnostic catheterization at hospitals without SoS, non-TVR was also
      increased (2.7% vs 1.9%, P=.002); there was no difference in myocardial
      infarction-driven TVR, non-TVR, or diagnostic catheterization. Predictors of 9
      month TVR included intra-aortic balloon pump use, any index PCI complication, and
      3-vessel PCI, whereas predictors of freedom from TVR included SoS, discharge on a
      P2Y12 inhibitor, and stent implantation. CONCLUSIONS: The noninferiority of
      nonprimary PCI at non-SoS hospitals was consistent across clinically relevant
      subgroups. Elective PCI at an SoS hospital conferred a TVR benefit which may be
      related to a lower rate of referral for diagnostic catheterization for reasons
      other than myocardial infarction.

PMID- 29447781
TI  - Prediction of long-term net clinical outcomes using the TIMI-AF score: Comparison
      with CHA2DS2-VASc and HAS-BLED.
AB  - : The TIMI-AF score was described to predict net clinical outcomes (NCOs) in
      atrial fibrillation (AF) patients receiving warfarin. However, this score derived
      from the ENGAGE AF-TIMI 48 trial, and no external validation exists in real world
      clinical practice. We tested the long-term predictive performance of the TIMI-AF
      score in comparison with CHA2DS2-VASc and HAS-BLED in a 'real-world' cohort of
      anticoagulated AF patients. METHODS: We included 1156 consecutive AF patients
      stable on vitamin K antagonist (INR 2.0-3.0) during 6 months. The baseline risk
      of NCOs (composite of stroke, life-threatening bleeding, or all-cause mortality)
      was calculated using the novel TIMI-AF score. During follow-up, all NCOs were
      recorded and the predictive performance and clinical usefulness of TIMI-AF was
      compared with CHA2DS2-VASc and HAS-BLED. RESULTS: During 6.5 years (IQR 4.3-7.9),
      there were 563 NCOs (7.49%/year). 'Low-risk' (6.07%/year) and 'medium-risk'
      (9.49%/year) patients defined by the TIMI-AF suffered more endpoints that low-
      and medium-risk patients of CHA2DS2-VASc and HAS-BLED (2.37%/year and 4.40%/year
      for low risk; 3.48%/year and 6.39%/year for medium risk, respectively). The
      predictive performance of TIMI-AF was not different from CHA2DS2-VASc (0.678 vs
      0.677, P = .963) or HAS-BLED (0.644 vs 0.671, P = .054). Discrimination and
      reclassification did not show improvement of prediction using the TIMI-AF score,
      and decision curves analysis did not demonstrate higher net benefit. CONCLUSIONS:
      In VKA-experienced AF patients, the TIMI-AF score has limited usefulness
      predicting NCOs over a long-term period of follow-up. This novel score was not
      superior to CHA2DS2-VASc and HAS-BLED identifying low-risk AF patients.

PMID- 29447782
TI  - Comparison of drug-eluting stents and drug-coated balloon for the treatment of
      drug-eluting coronary stent restenosis: A randomized RESTORE trial.
AB  - BACKGROUND: This study sought to evaluate the optimal treatment for in-stent
      restenosis (ISR) of drug-eluting stents (DESs). METHODS: This is a prospective,
      multicenter, open-label, randomized study comparing the use of drug-eluting
      balloon (DEB) versus second-generation everolimus-eluting stent for the treatment
      of DES ISR. The primary end point was in-segment late loss at 9-month routine
      angiographic follow-up. RESULTS: A total of 172 patients were enrolled, and 74
      (43.0%) patients underwent the angiographic follow-up. The primary end point was
      not different between the 2 treatment groups (DEB group 0.15+/-0.49 mm vs DES
      group 0.19+/-0.41 mm, P=.54). The secondary end points of in-segment minimal
      luminal diameter (MLD) (1.80+/-0.69 mm vs 2.09+/-0.46 mm, P=.03), in-stent MLD
      (1.90+/-0.71 mm vs 2.29+/-0.48 mm, P=.005), in-segment percent diameter stenosis
      (34%+/-21% vs 26%+/-15%, P=.05), and in-stent percent diameter stenosis (33%+/
      21% vs 21%+/-15%, P=.002) were more favorable in the DES group. The composite of
      death, myocardial infarction, or target lesion revascularization at 1 year was
      comparable between the 2 groups (DEB group 7.0% vs DES group 4.7%, P=.51).
      CONCLUSIONS: Treatment of DES ISR using DEB or second-generation DES did not
      differ in terms of late loss at 9-month angiographic follow-up, whereas DES
      showed better angiographic results regarding minimal MLD and percent diameter
      stenosis. Both treatment strategies were safe and effective up to 1year after the
      procedure.

PMID- 29447783
TI  - Representation of black patients in randomized clinical trials of heart failure
      with reduced ejection fraction.
AB  - BACKGROUND: Black individuals have a disproportionately higher burden of heart
      failure with reduced ejection fraction (HFrEF) relative to other racial and
      ethnic populations. We conducted a systematic review to determine the
      representation, enrollment trends, and outcomes of black patients in historic and
      contemporary randomized clinical trials (RCTs) for HFrEF. METHODS: We searched
      PubMed and Embase for RCTs of patients with chronic HFrEF that evaluated
      therapies that significantly improved clinical outcomes. We extracted trial
      characteristics and compared them by trial type. Linear regression was used to
      assess trends in enrollment among HFrEF RCTs over time. RESULTS: A total of 25
      RCTs, 19 for pharmacotherapies and 6 (n=9,501) for implantable cardioverter
      defibrillators, were included in this analysis. Among these studies, there were
      78,816 patients, 4,640 black (5.9%), and the median black participation per trial
      was 162 patients. Black race was reported in the manuscript of 14 (56.0%) trials,
      and outcomes by race were available for 12 (48.0%) trials. Implantable cardiac
      defibrillator trials enrolled a greater percentage of black patients than
      pharmacotherapy trials (7.1% vs 5.7%). Overall, patient enrollment among the 25
      RCTs increased over time (P = .075); however, the percentage of black patients
      has decreased (P = .001). Outcomes varied significantly between black and white
      patients in 6 studies. CONCLUSIONS: Black patients are modestly represented among
      pivotal RCTs of individuals with HFrEF for both pharmacotherapies and implantable
      cardioverter defibrillators. The current trend for decreasing black
      representation in trials of HF therapeutics is concerning and must improve to
      ensure the generalizability for this vulnerable population.

PMID- 29447784
TI  - Design of DISCO-Direct or Subacute Coronary Angiography in Out-of-Hospital
      Cardiac Arrest study.
AB  - BACKGROUND: Acute coronary syndrome is a common cause of out-of-hospital cardiac
      arrest (OHCA). In patients with OHCA presenting with ST elevation, immediate
      coronary angiography and potential percutaneous coronary intervention (PCI) after
      return of spontaneous circulation are recommended. However, the evidence for this
      invasive strategy in patients without ST elevation is limited. Observational
      studies have shown a culprit coronary artery occlusion in about 30% of these
      patients, indicating the electrocardiogram's (ECG's) limited sensitivity. The aim
      of this study is to determine whether immediate coronary angiography and
      subsequent PCI will provide outcome benefits in OHCA patients without ST
      elevation. METHODS/DESIGN: We describe the design of the DIrect or Subacute
      Coronary angiography in Out-of-hospital cardiac arrest study (DISCO)-a pragmatic
      national, multicenter, randomized, clinical study. OHCA patients presenting with
      no ST elevation on their first recorded ECG will be randomized to a strategy of
      immediate coronary angiography or to standard of care with admission to intensive
      care and angiography after 3days at the earliest unless the patient shows signs
      of acute ischemia or hemodynamic instability. Primary end point is 30-day
      survival. An estimated 1,006 patients give 80% power (alpha = .05) to detect a
      20% improved 30-day survival rate from 45% to 54%. Secondary outcomes include
      good neurologic recovery at 30days and 6months, and cognitive function and
      cardiac function at 6months. CONCLUSION: This randomized clinical study will
      evaluate the effect of immediate coronary angiography after OHCA on 30-day
      survival in patients without ST elevation on their first recorded ECG.

PMID- 29447786
TI  - High-sensitivity cardiac troponin T, left ventricular function, and outcome in
      non-ST elevation acute coronary syndrome.
AB  - BACKGROUND: Cardiac troponin (cTn) levels reflect infarct size and depressed left
      ventricular ejection fraction (LVEF) in patients with non-ST elevation acute
      coronary syndrome (NSTE-ACS). However, there is very limited information on
      whether cTn measured with a high-sensitivity (hs) assay would provide incremental
      prognostic information to the LVEF in NSTE-ACS patients. METHODS: This was a
      registry-based study (SWEDEHEART registry) investigating 20,652 NSTE-ACS patients
      with available information on hs-cTnT (highest level recorded during the
      hospitalization) and the LVEF estimated using echocardiography. All patients had
      been followed for 1 year. RESULTS: Hs-cTnT levels independently predicted major
      cardiovascular events (MACE) in cohorts with normal, slightly depressed,
      moderately depressed, and severely depressed LVEF. The adjusted hazard ratios in
      these cohorts were 1.18 (95% CI 1.13-1.23), 1.12 (95% CI 1.06-1.18), 1.12 (95% CI
      1.06-1.19), and 1.21 (95% CI 1.13-1.30), respectively. Hs-cTnT levels were
      particularly predictive for cardiovascular mortality and readmission for heart
      failure. Excluding patients with previous cardiac disease did not affect the
      overall interrelations of hs-cTnT and LVEF with MACE. CONCLUSIONS: Hs-cTnT levels
      provide incremental prognostic value independent of the LVEF in patients with
      NSTE-ACS. Hs-cTnT is particularly predictive for MACE in patients with severely
      depressed LVEF but also in those with a normal LVEF. Accordingly, a normal LVEF
      should not be used as an argument not to target patients to thorough workup.

PMID- 29447785
TI  - Association of lipoprotein-associated phospholipase A2 and risk of incident
      atrial fibrillation: Findings from 3 cohorts.
AB  - BACKGROUND: Multiple prospective studies have established an association between
      inflammation and higher risk of atrial fibrillation (AF), but the association
      between lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity and
      incident AF has not been extensively evaluated. METHODS: Using data from 10,794
      Atherosclerosis Risk In Communities (ARIC) study participants aged 53-75 years,
      5,181 Cardiovascular Health Study (CHS) participants aged 65 to 100 years, and
      5,425 Multi-Ethnic Study of Atherosclerosis (MESA) participants aged 45-84 years,
      we investigated the association between baseline Lp-PLA2 levels and the risk of
      developing AF. Incident AF was identified in each cohort by follow-up visit
      electrocardiograms, hospital discharge coding of AF, or Medicare claims data.
      RESULTS: Over a mean of 13.1, 11.5, and 10.0 years of follow-up, 1,439 (13%),
      2,084 (40%), and 615 (11%) incident AF events occurred in ARIC, CHS, and MESA,
      respectively. In adjusted analyses, each SD increment in Lp-PLA2 activity was
      associated with incident AF in both ARIC (hazard ratio [HR] 1.13, 95% CI 1.06
      1.20) and MESA (HR 1.24, 95% CI 1.05-1.46). Each SD increment in Lp-PLA2 mass was
      also associated with incident AF in MESA (HR 1.25, 95% CI 1.11-1.41). No
      significant associations were observed among CHS participants. CONCLUSIONS:
      Although higher Lp-PLA2 mass and activity were associated with development of AF
      in ARIC and MESA, this relationship was not observed in CHS, a cohort of older
      individuals.

PMID- 29447787
TI  - Rationale and design of the comparison between a P2Y12 inhibitor monotherapy
      versus dual antiplatelet therapy in patients undergoing implantation of coronary
      drug-eluting stents (SMART-CHOICE): A prospective multicenter randomized trial.
AB  - BACKGROUND AND RATIONALE: Dual antiplatelet therapy (DAPT) with aspirin and a
      P2Y12 inhibitor reduces thrombotic events in patients undergoing percutaneous
      coronary intervention (PCI), but these benefits come at the expense of increased
      risk of bleeding when compared with aspirin monotherapy. It is unclear whether
      P2Y12 inhibitor monotherapy might maintain anti-ischemic efficacy while reducing
      the bleeding risk compared with DAPT after implantation of the current generation
      of drug-eluting stents (DES). STUDY DESIGN: The SMART-CHOICE trial is a
      prospective, open-label, multi-center, and randomized study designed to test the
      non-inferiority of P2Y12 inhibitor monotherapy compared with aspirin plus a P2Y12
      inhibitor after mandatory 3-month DAPT in patients undergoing PCI with current
      generation DES. A total of 3000 patients will be randomized to 1 of the 2
      antiplatelet treatment strategy groups. Randomization will be stratified by stent
      type (cobalt-chromium everolimus-eluting stents, platinum-chromium everolimus
      eluting stents, and sirolimus-eluting stents with bioresorbable polymer), P2Y12
      inhibitors (clopidogrel, prasugrel, and ticagrelor), clinical presentation (acute
      coronary syndrome and stable ischemic heart disease), and investigational
      centers. The primary end point is a composite of all-cause death, myocardial
      infarction, and cerebrovascular events at 12 months after the index procedure.
      The key secondary end points are definite/probable stent thrombosis defined by
      the Academic Research Consortium, and bleeding defined by Bleeding Academic
      Research Consortium type 2-5. CONCLUSIONS: The SMART-CHOICE trial aims to examine
      the non-inferiority of monotherapy with one of any available oral P2Y12
      inhibitors versus conventional DAPT of an identical P2Y12 inhibitor plus aspirin
      in a broad spectrum of patients receiving representative current-generation DES.

PMID- 29447788
TI  - The influence of febuxostat on coronary artery endothelial dysfunction in
      patients with coronary artery disease: A phase 4 randomized, placebo-controlled,
      double-blind, crossover trial.
AB  - BACKGROUND: The xanthine oxidase (XO) system is a significant source of vascular
      oxidative stress, which is believed to impair endothelial function, an important
      contributor to atherosclerotic disease. We tested whether febuxostat, a potent XO
      inhibitor, improves coronary endothelial function (CEF) in patients with stable
      coronary artery disease (CAD) in a single-center, randomized, placebo-controlled,
      double-blind crossover trial. METHODS: CEF was measured using noninvasive
      magnetic resonance imaging (MRI) assessment of changes in 30 patients with stable
      CAD and baseline impaired CEF. Patients received either febuxostat or placebo for
      6 weeks and then were crossed over to the alternative for an additional 6 weeks.
      MRI-detected changes in coronary flow and in coronary cross-sectional area from
      rest to isometric handgrip exercise, a known endothelial-dependent stressor, were
      measured at the end of each 6 week period. RESULTS: Mean serum urate levels were
      lower at the end of the 6-week febuxostat period (2.9+/-0.8mg/dL) than at the end
      of the 6-week placebo period (5.9+/-0.04, P<.001). However, there were no
      significant differences in any of the CEF parameters measured at the end of the
      febuxostat and placebo periods. CONCLUSIONS: In summary, although XO inhibition
      with febuxostat was well tolerated and lowered serum urate, it did not improve
      the primary end point of the study, CEF measured using MRI after 6 weeks of
      treatment. In conclusion, these findings suggest that short-term inhibition of XO
      does not significantly improve impaired CEF in patients with stable CAD.

PMID- 29447789
TI  - Comprehensive electrocardiogram-to-device time for primary percutaneous coronary
      intervention in ST-segment elevation myocardial infarction: A report from the
      American Heart Association mission: Lifeline program.
AB  - BACKGROUND: Assessing hospital-related network-level primary percutaneous
      coronary intervention (PCI) performance for ST-segment elevation myocardial
      infarction (STEMI) is challenging due to differential time-to-treatment metrics
      based on location of diagnostic electrocardiogram (ECG) for STEMI. METHODS: STEMI
      patients undergoing primary PCI at 588 PCI-capable hospitals in AHA Mission:
      Lifeline (2008-2013) were categorized by initial STEMI identification location:
      PCI-capable hospitals (Group 1); pre-hospital setting (Group 2); and non-PCI
      capable hospitals (Group 3). Patient-specific time-to-treatment categories were
      converted to minutes ahead of or behind their group-specific mean; average time
      to-treatment difference for all patients at a given hospital was termed
      comprehensive ECG-to-device time. Hospitals were then stratified into tertiles
      based on their comprehensive ECG-to-device times with negative values below the
      mean representing shorter (faster) time intervals. RESULTS: Of 117,857 patients,
      the proportion in Groups 1, 2, and 3 were 42%, 33%, and 25%, respectively. Lower
      rates of heart failure and cardiac arrest at presentation are noted within
      patients presenting to high-performing hospitals. Median comprehensive ECG-to
      device time was shortest at -9 minutes (25th, 75th percentiles: -13, -6) for the
      high-performing hospital tertile, 1 minute (-1, 3) for middle-performing, and 11
      minutes (7, 16) for low-performing. Unadjusted rates of in-hospital mortality
      were 2.3%, 2.6%, and 2.7%, respectively, but the adjusted risk of in-hospital
      mortality was similar across tertiles. CONCLUSIONS: Comprehensive ECG-to-device
      time provides an integrated hospital-related network-level assessment of
      reperfusion timing metrics for primary PCI, regardless of the location for STEMI
      identification; further validation will delineate how this metric can be used to
      facilitate STEMI care improvements.

PMID- 29447790
TI  - Fine particulate matter and incident coronary heart disease in the REGARDS
      cohort.
AB  - : Chronic exposure to fine particulate matter (PM2.5) is accepted as a causal
      risk factor for coronary heart disease (CHD). However, most of the evidence for
      this hypothesis is based upon cohort studies in whites, comprised of either only
      males or females who live in urban areas. It is possible that many estimates of
      the effect of chronic exposure to PM2.5 on risk for CHD do not generalize to more
      diverse samples. METHODS: Therefore, we estimated the relationship between
      chronic exposure to PM2.5 and risk for CHD in among participants in the REasons
      for Geographic And Racial Differences in Stroke (REGARDS) cohort who were free
      from CHD at baseline (n=17,126). REGARDS is a sample of whites and blacks of both
      genders living across the continental United States. We fit Cox proportional
      hazards models for time to CHD to estimate the hazard ratio for baseline 1-year
      mean PM2.5 exposure, adjusting for environmental variables, demographics, and
      other risk factors for CHD including the Framingham Risk Score. RESULTS: The
      hazard ratio (95% CI) for a 2.7-MUg/m3 increase (interquartile range) 1-year mean
      concentration of PM2.5 was 0.94 (0.83-1.06) for combined CHD death and nonfatal
      MI, 1.13 (0.92-1.40) for CHD death, and 0.85 (0.73-0.99) for nonfatal MI. We also
      did not find evidence that these associations depended upon overall CHD risk
      factor burden. CONCLUSIONS: Our results do not provide strong evidence for an
      association between PM2.5 and incident CHD in a heterogeneous cohort, and we
      conclude that the effects of chronic exposure to fine particulate matter on CHD
      require further evaluation.

PMID- 29447791
TI  - Re: Are Modic changes associated with intervertebral disc cytokine profiles?

PMID- 29447792
TI  - Diabetes and quality of life in patients with lumbar decompression surgery.

PMID- 29447793
TI  - Clinical role of vitamin D in prognosis of otitis media with effusion.
AB  - OBJECTIVE: To investigate the clinical role of Vitamin D in prognosis of Otitis
      media with effusion. METHODS: This prospective-controlled study was conducted at
      otolaryngology department in Duzce University, Turkey. The study group comprised
      children who were diagnosed with Otitis media with effusion between September
      2016 and February 2017. Control group was conducted with children underwent
      circumcision or inguinal hernia repair operations that confirmed with ENT
      examination they do not have any sign of otitis media. After 3 months of follow
      up without any treatment, unresolved cases who were accepted as chronic otitis
      media with effusion were operated under general anesthesia for ventilation tube
      application. Study and control groups were assessed depending on the serum
      25(OH)Vitamin D levels at the end of 3 months; < 15 ng/mL was accepted as vitamin
      D deficiency. The results were compared with the control group in terms of
      vitamin D levels. Also, subgroup analysis was performed addressing to the
      complete recovery otitis media with effusion and chronic otitis media with
      effusion. RESULTS: One-hundred-seventy-four children with otitis media with
      effusion and 80 control patients were included to the study. One-hundred-eight
      (62%) out of 174 patients with otitis media with effusion was completely
      recovered after a 3-months follow up. Of those 66 out of 174 children, they had
      persistent diseases, underwent ventilation tube insertion after a 3-months follow
      up. The mean 25(OH)Vitamin D level was 18.98 +/- 10.60 in otitis media with
      effusion group and 28.07 +/- 14.10 in control group and the difference was
      statistically significant between the study and control group (p < 0.001).
      Vitamin D deficiency was observed in 33 out of 66 patients (50.0%) in chronic
      otitis media with effusion group whilst 35 out of 108 patients (32.4%) in
      complete recovery otitis media with effusion group (p = 0.021). The rate of
      25(OH)Vitamin D deficiency was 25% in control group which was statistically
      different from chronic otitis media with effusion and recovery chronic otitis
      media with effusion groups (p = 0.006). CONCLUSIONS: This study not only shows
      the relationship between Vitamin D and otitis media with effusion development,
      but also demonstrates the effects of Vitamin D on otitis media with effusion
      prognosis. There is a significant association between 25(OH)Vitamin D deficiency
      and follow-up outcomes of otitis media with effusion.

PMID- 29447794
TI  - Plasticity after pediatric cochlear implantation: Implication from changes in
      peripheral plasma level of BDNF and auditory nerve responses.
AB  - INTRODUCTION: Sensory neural hearing loss could lead to some structural and
      physiological changes in the auditory pathways, such as alteration in the
      expression of neurotrophins. These factors, especially Brain-Derived Neurotrophic
      Factor (BDNF), play an important role in synaptic functions and experience
      related plasticity. Restoring cochlear function after hearing loss is possible
      through cochlear implantation (CI). Evaluation of the blood concentration changes
      of neurotrophins as prerequisites of plasticity could help scientists to
      determine the prognosis of CI as in the candidacy procedure or enhancing
      prosthesis function by adding the exact needed amount of BDNF to the electrode
      array. METHODS: Here we have studied the plasma BDNF concentration before CI
      surgery and 6 months after using CI device in 15 pediatric CI recipients and
      compared this level with changes of BDNF concentration in 10 children who were
      using hearing aid (H.A). In addition, we searched for a possible correlation
      between post-surgery plasma BDNF concentration and electrical compound action
      potential (ECAP) and comfort-level (C-level) thresholds. RESULTS: Plasma BDNF
      concentration in children with CI increased significantly after CI surgery, while
      this difference in H.A group was not significant. Analysis of repeated measures
      of ECAP and C-level thresholds in CI group showed that there were some kinds of
      steadiness during follow- up sessions for ECAP thresholds in basal and E16 of
      middle electrodes, whereas C-level thresholds for all selected electrodes
      increased significantly up to six months follow-up. Interestingly, we did not
      find any significant correlation between post-surgery plasma BDNF concentration
      and ECAP or C-level threshold changes. CONCLUSION: It is concluded that changes
      in C-level threshold and steady state of ECAP thresholds and significant changes
      in BDNF concentration could be regarded as an indicator of experienced-related
      plasticity after CI stimulation.

PMID- 29447795
TI  - Modified approach for pediatric external cricopharyngeal myotomy.
AB  - Pediatric cricopharyngeal achalasia is an uncommon but important cause of
      oropharyngeal dysphagia. Failure of upper esophageal sphincter relaxation is the
      currently understood pathophysiology. Therapies include balloon dilation,
      botulinum toxin injection, and endoscopic or open cricopharyngeal myotomy (CPM).
      Open CPM is usually performed at the posterior midline of the cricopharyngeus and
      can be a risky procedure given concern for esophageal perforation and damage to
      the recurrent laryngeal nerve. Here, we present a novel modified technique for
      open CPM using a superficial anterolateral transection approach in the case of a
      young male with refractory cricopharyngeal achalasia.

PMID- 29447796
TI  - Endoscopic transpterygoid approach to a mass in a child.
AB  - The endoscopic transterygoid approach to the petrous apex is a
      feasible/alternative approach in carefully selected patients with specific
      favorable anatomy, even children. This approach, unlike traditional approaches,
      spares cochlear and vestibular function. We report a case of a six-year-old boy
      with embryonal rhabdomyosarcoma of the petrous apex that was diagnosed via the
      endoscopic transpterygoid approach.

PMID- 29447797
TI  - The anatomic applicability of transcanal endoscopic ear surgery in children.
AB  - OBJECTIVE: The feasibility of TEES in dealing with pediatric middle ear disease
      is still under investigation. The goal of this study was to compare anatomical
      dimensions of the EAC between children and adults, and to analyze the anatomic
      applicability of TEES in children. METHODS: Forty pediatric (18 years old and
      younger) and 20 adult patients who received TB-HRCT to evaluate middle ear
      conditions were enrolled from December 2010 to December 2015. Dimensions
      including the diameters of the EAC orifice, isthmus and tympanic membrane
      annulus, the length of EAC, the height of the middle ear, and the angle between
      tympanic membrane and EAC axis were determined according to the TB-HRCT data.
      RESULTS: The diameters of the EAC orifice and isthmus and length of EAC in the
      pediatric patients were slightly smaller than those in the adult patients. The
      anatomical dimensions of middle ear were similar in both groups. Simple
      regression analysis indicated that the diameters of the EAC orifice and isthmus
      and the length of the EAC were positively correlated with the age of the
      pediatric patients. In the pediatric patients, 67 ears (83.75%) had an EAC
      isthmus diameter larger than 4 mm and are sufficient with a 3-mm endoscope
      manipulation. CONCLUSION: TEES is applicable for most pediatric patients using an
      endoscope with a diameter of 3 mm or smaller. With an appropriate endoscope and
      instruments, TEES is a safe and effective alternative to treat pediatric middle
      ear disease.

PMID- 29447798
TI  - Papillary thyroid carcinoma presenting as acute suppurative thyroiditis: A case
      report and review of the literature.
AB  - Acute suppurative thyroiditis is a rare, potentially life-threatening condition.
      We report the case of a 17-year-old male who initially presented with a thyroid
      abscess. Due to persistent symptoms and lack of evidence for underlying
      predisposing factors, he was followed closely and subsequently diagnosed with
      papillary thyroid cancer. He was successfully managed with surgery. His clinical
      course, radiological evaluation, and pathology reports are presented here along
      with a review of the literature. This case of papillary thyroid cancer highlights
      the need for close follow-up of patients presenting with a thyroid abscess, when
      other predisposing risk factors are not evident.

PMID- 29447799
TI  - Iatrogenic Cushing's syndrome and adrenal insufficiency in infants on intranasal
      dexamethasone drops for nasal obstruction - Case series and literature review.
AB  - The use of intranasal steroid drops for nasal obstruction in infants is common
      practice and can prevent more invasive surgical procedures; however, it is not
      without complication. We describe 2 cases of iatrogenic Cushing's secondary to
      nasal steroids in infants with nasal obstruction, discuss the etiology of this
      unusual complication, and review previous literature reports. While reporting in
      the literature is sparse, these cases highlight the risk of development of
      adrenal insufficiency with usage of nasal steroid drops in infants as well as the
      need for close monitoring of administration and tapering of the drops.
      Additionally, we suggest an approach to the infant with symptomatic nasal
      obstruction that addresses the usage of intranasal steroid drops and emphasizes
      the need for quick tapering and possible endocrine consultation when appropriate.

PMID- 29447800
TI  - Reliability and validity of the Chinese pediatric voice handicap index.
AB  - OBJECTIVES: To evaluate the reliability and validity of the Chinese version of
      pediatric voice handicap index (pVHI). MATERIAL AND METHODS: The original English
      version-pVHI was translated into Chinese. Parents of 52 children with voice
      dysphonia and 43 children with no history or symptoms of voice problems were
      asked to fill the Chinese pVHI questionnaires twice with an interval of 2 weeks.
      GRB (Grade, Roughness, Breathiness) scale was used for perceptual assessment by
      two otolaryngologists and one speech pathologist for each child's voice. The
      internal consistency was assessed using Cronbach's alpha coefficient. Pearson's
      correlation coefficient was used to evaluate the test-retest reliability. The
      Kendall's coefficient of concordance W was used to assess the consistency of GRB
      scores of 3 voice specialists. The nonparametric Mann-Whitney test was used to
      assess the differences between the dysphonia group and controls. The correlation
      between pVHI and GRB scores were assessed using Pearson's correlation
      coefficient. RESULTS: The internal consistency of total score and three subscales
      scores of Chinese pVHI were 0.788-0.944. The test-retest reliability was 0.631
      0.887(P < .001). The pVHI scores of control group significantly were lower than
      the pathological group (P = .000). The GRB scores of 3 voice specialists have an
      excellent consistency (W = 0.694-0.807, P = .000). The pVHI scores positively
      correlated with GRB assessment (P < .01). CONCLUSIONS: The Chinese version of
      pVHI had a good reliability and validity. It can be applicable and useful
      supplementary tool for evaluating parents' perception of their children's
      dysphonia.

PMID- 29447801
TI  - A clinical pathway for the postoperative management of hypocalcemia after
      pediatric thyroidectomy reduces blood draws.
AB  - OBJECTIVES: Postoperative calcium management is challenging following pediatric
      thyroidectomy given potential limitations in self-reporting symptoms and
      compliance with phlebotomy. A protocol was created at our tertiary children's
      institution utilizing intraoperative parathyroid hormone (PTH) levels to guide
      electrolyte management during hospitalization. The objective of this study was to
      determine the effect of a new thyroidectomy postoperative management protocol on
      two primary outcomes: (1) the number of postoperative calcium blood draws and (2)
      the length of hospital stay. STUDY DESIGN: Institutional review board approved
      retrospective study (2010-2016). METHODS: Consecutive pediatric total
      thyroidectomy and completion thyroidectomy +/- neck dissection cases from
      1/1/2010 through 8/5/2016 at a single tertiary children's institution were
      retrospectively reviewed before and after initiation of a new management
      protocol. All cases after 2/1/2014 comprised the experimental group (post
      protocol implementation). The pre-protocol control group consisted of cases prior
      to 2/1/2014. Multivariable linear and Poisson regression models were used to
      compare the control and experimental groups for outcome measure of number of
      calcium lab draws and hospital length of stay. RESULTS: 53 patients were included
      (n = 23, control group; n = 30 experimental group). The median age was 15 years.
      41 patients (77.4%) were female. Postoperative calcium draws decreased from a
      mean of 5.2 to 3.6 per day post-protocol implementation (Rate Ratio = 0.70, p <
      .001), adjusting for covariates. The mean number of total inpatient calcium draws
      before protocol initiation was 13.3 (+/-13.20) compared to 7.2 (+/-4.25) in the
      post-protocol implementation group. Length of stay was 2.1 days in the control
      group and 1.8 days post-protocol implementation (p = .29). Patients who underwent
      concurrent neck dissection had a longer mean length of stay of 2.32 days compared
      to 1.66 days in those patients who did not undergo a neck dissection (p = .02).
      Hypocalcemia was also associated with a longer mean length of stay of 2.41 days
      compared to 1.60 days in patients who did not develop hypocalcemia (p < .01).
      CONCLUSIONS: The number of calcium blood draws was significantly reduced after
      introduction of a standardized protocol based on intraoperative PTH levels. The
      hospital length of stay did not change. Adoption of a standardized postoperative
      protocol based on intraoperative PTH levels may reduce the number of blood draws
      in children undergoing thyroidectomy.

PMID- 29447802
TI  - Effects of maxillary protraction appliances on airway dimensions in growing class
      III maxillary retrognathic patients: A systematic review and meta-analysis.
AB  - OBJECTIVES: The purpose of this study was to assess, through a systematic review
      and meta-analysis, the efficacy of maxillary protraction appliances (MPAs) on
      improving pharyngeal airway dimensions in growing class III patients with
      maxillary retrognathism. METHODS: An electronic search in PubMed, Cochrane
      Library, Web of Science, and EMBASE was until September 2nd, 2017. The
      assessments of methodological quality of the selected articles were performed
      using the Newcastle-Ottawa Scale. Review Manager 5.3 (provided by the Cochrane
      Collaboration) was used to synthesize the effects of MPAs on pharyngeal airway
      dimensions. RESULTS: Following full-text articles evaluation for eligibility, 6
      studies (168 treated subjects and 140 untreated controls) were included in final
      quantitative synthesis and they were all high-quality. Compared to untreated
      control groups, the treatment groups had increased significantly nasopharyngeal
      airway dimensions with the following measurements: PNS-AD1 (fixed: mean
      difference, 1.33 mm, 95% CI, 0.48mm-2.19 mm, P = .002), PNS-AD2 (random: mean
      difference, 1.91 mm, 95% CI, 0.02mm-3.81 mm, P = .05), aerial nasopharyngeal area
      (fixed: mean difference, 121.91 mm2, 95% CI, 88.70 mm2-155.11 mm2, P < .00001)
      and total nasopharyngeal area (fixed: mean difference, 142.73 mm2, 95% CI, 107.90
      mm2-177.56 mm2, P < .00001). Meanwhile, McNamara's upper pharynx dimension
      (fixed: mean difference, 0.96 mm, 95% CI, 0.29mm-1.63 mm, P = .005), which was
      highly related to post-palatal airway dimension, was also improved significantly.
      However, no statistically significant differences in adenoidal nasopharyngeal
      area (P > .05) and McNamara's lower pharynx dimension (P > .05) existed.
      CONCLUSIONS: MPAs can increase post-palatal and nasopharyngeal airway dimensions
      in growing skeletal class III subjects with maxillary retrusion. It may be
      suggested that MPAs have the potential to reduce the risk of obstructive sleep
      apnea syndrome in children with maxillary retrusion by enlarging airway space.

PMID- 29447803
TI  - Maternal knowledge and attitudes to universal newborn hearing screening:
      Reviewing an established program.
AB  - OBJECTIVES: To facilitate early diagnosis of infants with hearing loss, a
      universal newborn hearing screening program (UNHS) has been implemented in Hong
      Kong's public hospitals for over a decade. However, there have been no known
      studies investigating parent attitudes to, and satisfaction with, UNHS since its
      launch in Hong Kong. The present study aimed to investigate knowledge of UNHS as
      well as infant hearing development, and attitudes and satisfaction with UNHS, in
      Hong Kong mothers with newborns. The study was designed to help evaluate and
      improve an established UNHS public hospital program, based on the perspectives of
      service users. METHODS: A researcher-developed questionnaire was administered to
      102 mothers whose newborn had received UNHS in the postnatal wards of a large
      public hospital in Hong Kong. The questionnaire considered parental knowledge of
      UNHS and infant hearing development, attitudes and satisfaction toward public
      hospital UNHS. In the knowledge dimension, parents' preferred time and location
      for pre-test information delivery, interpretation of screening results, and
      knowledge of hearing developmental milestones were surveyed. In addition,
      maternal attitudes to and satisfaction with UNHS screening services, the
      potential impact of UNHS on parent emotions and parent-baby bonding, attitudes
      toward informed consent, and willingness to comply with diagnostic assessment
      referral were also be surveyed. RESULTS: Mean participant scores on knowledge of
      infant hearing development were relatively low (M = 2.59/6.0, SD = 0.90). Many
      mothers also underestimated the potential ongoing risks of hearing impairment in
      babies. Around 80% of mothers thought an infant could not have hearing impairment
      after passing the screening. In addition, one-third of mothers thought a baby
      could not later develop hearing impairment in infancy or childhood. In terms of
      attitudes and satisfaction, participants gave somewhat negative ratings for
      questions regarding receiving sufficient information about the screening (M =
      2.90/5.0, SD = 1.27), screening procedure (M = 2.20/5.0, SD = 1.08), and
      sufficiency of information about results (M = 2.87/5.0, SD = 1.14). Nonetheless,
      participants gave positive ratings concerning whether screening could lead to
      early diagnosis (M = 4.61/5.0, SD = 0.57) and over 95% of mothers supported UNHS
      despite potential for false positive results. Mothers reported a high willingness
      to bring their baby to follow-up assessments if required (M = 4.53/5.0, SD =
      0.56). Participants gave positive ratings for their level of satisfaction with
      the time and location of first UNHS information provision (M = 4.34/5.0, SD =
      0.80) and the way permission was asked for screening the baby (M = 4.04/5.0, SD =
      0.97) but alternative procedures were also recommended. Most recommendations
      focused on providing more information about the test and a more detailed
      explanation of screening results. CONCLUSIONS: The survey results highlighted the
      need to provide more information to parents about infant hearing development to
      support home monitoring for signs of hearing loss after UNHS, as well as more
      detailed explanation and information regarding hearing screening and the
      implications of results to parents. Regardless of location, surveys of this type
      may provide valuable support for UNHS program quality assurance.

PMID- 29447804
TI  - Long-term follow-up with mention of complications in pediatric microvascular
      mandibular reconstruction.
AB  - The fibular free flap has become the gold standard for mandibular reconstruction.
      Despite its vast array of benefits, this procedure has the potential for several
      complications. In the pediatric setting, the immature skeleton sets the stage for
      an increased risk of future skeletal abnormalities, both in the jaw, and in the
      donor site. Herein we describe the case of a toddler who underwent mandibular
      reconstruction using a fibula free flap and, years later, subsequently developed
      ankle instability as a result of residual fibula migration. This indicates the
      need for careful consideration of long-term issues in the growing pediatric
      skeleton prior to surgery.

PMID- 29447805
TI  - Characterization of newborn hearing screening failures in multigestational
      births.
AB  - OBJECTIVE: To define the rate and characterize the type of newborn hearing
      screening failures in multigestational births. METHODS: Retrospective chart
      review of all multigestational births that occurred in a 10-year period (2002
      2012) in which at least one newborn failed newborn hearing screening at two
      tertiary care hospitals in the Northwell Health System. RESULTS: Out of 125,405
      total births, we identified 2961 multigestational births, of which 59 (2.0%)
      newborns failed newborn hearing screening. None of their 66 twin/triplet siblings
      failed their newborn hearing screens. Of 43 newborns that returned for follow-up,
      56.0% (24/43) had confirmed hearing loss, resulting in an overall rate of 0.81%
      in all multigestational newborns with hearing loss. Of 19 infants that passed
      repeat testing, two were judged to need myringotomy tube placement. Twenty-four
      infants had a confirmed hearing loss, 11 of which had sensorineural hearing loss
      (0.37%), and 13 with a conductive or mixed hearing loss (0.44%). CONCLUSIONS: We
      identified a greater than expected risk of conductive hearing loss, not
      attributable to otitis media, than sensorineural hearing loss in this population.
      These observations are consistent with the increased risk of birth defects in
      multigestational births.

PMID- 29447806
TI  - Pediatric Meniere's disease.
AB  - OBJECTIVE: This study adopted an inner ear test battery comprising audiometry,
      and ocular vestibular evoked myogenic potential (oVEMP), cervical VEMP (cVEMP),
      and caloric tests to investigate the sequence of inner ear deficits in pediatric
      Meniere's disease (MD). METHODS: From 2005 to 2016, a total of 24 MD children
      aged <15 years old underwent otoscopy, CT scan, blood test, and an inner ear test
      battery. Nine subjects were males and 15 were females, with mean age of 12 years.
      Right ear was affected in 3 patients, left ear in 5 patients, and both ears in 16
      patients (67%). Eight (33%) of the 24 MD children had positive family history.
      RESULTS: Inner ear deficits in MD children ran from abnormal hearing (25%) to
      abnormal cVEMP (20%), oVEMP (13%), and caloric (12%) tests, exhibiting a
      significantly declining sequence from the cochlea, to the saccule, utricle and
      semicircular canals. Analysis between the laterality and family history revealed
      a significantly positive correlation. CONCLUSION: Pediatric MD is rare,
      accounting for 2.3% prevalence in MD patients. The inner ear deficits in
      pediatric MD showed a significantly declining sequence from the cochlea, to the
      saccule, utricle and semicircular canals, mimicking the sequence in adult MD. One
      third MD children had positive family history, which may explain the high rate of
      bilateral affliction and symmetrical hearing levels on both ears.

PMID- 29447807
TI  - Sialoendoscopy for treatment of juvenile recurrent parotitis: The Brescia
      experience.
AB  - OBJECTIVE: To evaluate the role of sialoendoscopy associated with steroid
      irrigation for juvenile recurrent parotitis (JRP) at a tertiary referral
      hospital. METHODS: Clinical records of patients affected by JRP and treated with
      operative sialoendoscopy between June 2011 and April 2017 were retrospectively
      reviewed. Data on demographics, number of acute episodes per year before and
      after surgery, characteristics of the surgical procedure, hospitalization time,
      and rate of complications were collected. The outcome of the procedure was
      measured by comparing the number of episodes of parotid swelling before and after
      salivary endoscopic treatment. RESULTS: Twenty-three patients for a total of 34
      operative sialoendoscopies were included in the study. Before the surgical
      endoscopic procedure, the mean number of parotid swelling was 10 episodes per
      year. At sialoendoscopy, typical endoscopic findings such as mucous plugs,
      stenosis of the duct, intraductal debris, and pale ductal appearance were
      evident. All patients were discharged on the first postoperative day. A
      significant decrease in the number of swelling episodes per year was observed
      compared to the preoperative rate (p = .0004). Complete resolution of the
      disorder was obtained in 35% of patients. CONCLUSIONS: Operative sialoendoscopy
      with steroid irrigation can be considered a valid therapeutic treatment for JRP.
      The technique is conservative, effective, safe, and, potentially repeatable.
      Short hospitalization time, rapid recovery, absence of peri-operative
      complications, and a high rate of good outcomes are the main advantages of this
      treatment.

PMID- 29447808
TI  - Hold your horses: A comparison of human laryngomalacia with analogous equine
      airway pathology.
AB  - OBJECTIVES: Laryngomalacia is the most common cause of stridor in infants.
      Dynamic airway collapse is also a well-recognised entity in horses and an
      important cause of surgical veterinary intervention. We compare the aetiology,
      clinical features and management of human laryngomalacia with equine dynamic
      airway collapse. METHODS: A structured review of the PubMed, the Ovid Medline and
      the Cochrane Collaboration databases (Cochrane Central Register of Controlled
      Trials, Cochrane Database of Systemic Reviews). RESULTS: There are numerous
      equine conditions that cause dynamic airway collapse defined specifically by the
      anatomical structures involved. Axial Deviation of the Aryepiglottic Folds (ADAF)
      is the condition most clinically analogous to laryngomalacia in humans, and is
      likewise most prevalent in the immature equine airway. Both conditions are
      managed either conservatively, or if symptoms require it, with surgical
      intervention. The operative procedures performed for ADAF and laryngomalacia are
      technically comparable. CONCLUSION: Dynamic collapse of the equine larynx,
      especially ADAF, is clinically similar to human laryngomalacia, and both are
      treated in a similar fashion.

PMID- 29447809
TI  - Difficult airway intubation simulation using Bonfils fiberscope and rigid
      fiberscope for surgical training.
AB  - INTRODUCTION: Pediatric otolaryngologists are frequently called to assist in
      difficult airway management in newborns with Pierre Robin Sequence (PRS) who have
      microretrognathia, glossoptosis, and an anterior larynx. The Bonfils fiberscope
      (BF) is a curved rigid scope designed to provide superior visualization in the
      anterior larynx. OBJECTIVE: (1) to assess whether BF provides an improvement in
      intubation success rate, time to intubation, or airway visualization as compared
      to rigid fiberscope (RF) in a difficult airway simulation setting and (2) to
      determine whether a training program for BF can improve time to intubation
      through practice trials. METHODS: Six right-handed trainees completed five trials
      on each of the three following airway models using the BF and RF: normal anatomy,
      anterior larynx and PRS. The normal larynx model was intubated only with RF. Main
      outcome measures were the time needed for tracheal intubation and Cormack-Lehane
      classification (1-4). RESULTS: The majority of the intubation trials showed a
      statistically significant difference between first and last completion times (p <
      .05) suggesting construct validity. Only the anterior larynx trials with BF did
      not demonstrate an improvement in time to intubation between first and last
      attempts (p < .3125). For the PRS retrognathia model, there was no statistically
      significant difference in time to intubation between using the BF and the RF (p <
      .44); in the anterior larynx model, the RF yielded a faster time to intubation
      than the BF on the final trial attempts (p < .0313). By Cormack-Lehane
      classification measures, laryngeal visualization by the BF was better than RF in
      the PRS manikin (p < .0022) while there was no significant difference in grade
      scores for the anterior larynx manikin (p < .45). All six trainees reported an
      improved visualization of the larynx with the BF compared to the RF for both the
      anterior larynx and PRS manikins; at the end of the trial runs, all participants
      noted an improvement in comfort level using the BF. CONCLUSION: The difficult
      airway simulation model is feasible for surgical training. BF adds superior
      visualization of the anterior larynx in PRS. Otolaryngology training programs may
      include BF as a supplemental tool in addition to RF as a part of the airway
      equipment training since there is significant improvement in time to intubation
      with consecutive practice trials and superior laryngeal visualization.

PMID- 29447810
TI  - No evidence of cholesteatoma in untreated otitis media with effusion in children
      with primary ciliary dyskinesia.
AB  - INTRODUCTION: Primary Ciliary Dyskinesia (PCD) describes a group of inherited
      disorders that result in abnormal ciliary motion leading to mucous stasis.
      Clinical features include almost universally otitis media with effusion (OME),
      particularly in infants. PCD patients provide us with a cohort of patients with
      OME that is not treated with ventilatory tube (VT) insertion as these have been
      shown to result in frequent complications including chronic otorrhoea, early
      extrusion and persistent perforation without significant improvement to hearing
      in the long term. This cohort was used to investigate whether children with PCD
      and OME not treated with VT were predisposed to cholesteatoma formation in the
      setting of a paediatric quaternary referral centre. METHODS: A retrospective
      chart review was performed of all the children attending a multi-disciplinary PCD
      clinic at a national quaternary referral centre with a diagnosis of OME. We
      reviewed otoscopic findings, and audiometry and tympanometry results. We assessed
      the children in four groups: Watchful waiting, hearing aids, VT, and VT and
      hearing aids. RESULTS: One-hundred-and-one of 107 patients included in the study
      had a diagnosis of otitis media with effusion. No child with OME and PCD was
      diagnosed with a cholesteatoma during the follow up period. The only children who
      had insertion of a ventilatory tube were those who had the procedure prior to the
      formal diagnosis of PCD. We found a significant complication rate in the children
      with VT insertion. Hearing improved over time. The prevalence of retraction
      pockets in untreated OME was 1.72% (3 out of 174 ears). CONCLUSIONS: In children
      with PCD, OME is an almost universal finding in younger children, but not in
      adolescents. The study supports the current preference to avoid VT insertion in
      children with PCD as it confers a significantly higher rate of complications. No
      cases of cholesteatoma were found in this cohort of PCD children with OME managed
      without VTs.

PMID- 29447811
TI  - Sensorineural and conductive hearing loss in infants diagnosed in the program of
      universal newborn hearing screening.
AB  - OBJECTIVE: The aim of this study was to analyze infants diagnosed with
      sensorineural or conductive hearing deficit and to identify risk factors
      associated with these defects. MATERIAL AND METHODS: A retrospective analysis of
      infants diagnosed with hearing deficit based on the database of the universal
      newborn hearing screening program and medical records of the patients. RESULTS:
      27 935 infants were covered by the universal neonatal hearing screening program.
      109 (0.39%) were diagnosed with hearing deficit and referred for treatment and
      rehabilitation. 56 (51.4%) children were diagnosed with conductive, 38 (34.9%)
      with sensorineural and 15 (13.8%) with mixed type of hearing deficit. Children
      with sensorineural hearing deficit more frequently suffered from
      hyperbilirubinemia (p < 0.05), while infants with conductive hearing loss were
      more frequently diagnosed with isolated craniofacial anomalies (p < 0.05). The
      prevalence of other risk factors did not differ between the groups. Sensorineural
      hearing deficit occurred almost 3 times more often bilaterally than unilaterally
      (p < 0.05). In other types of hearing deficit, the difference was not
      significant. In children with conductive and mixed type of hearing loss the
      impairment was mainly mild while among those with sensorineural hearing deficit
      in almost 45% it was severe and profound (p < 0.05). When analyzing the
      consistency between hearing screening test by means of otoacoustic emissions and
      the final diagnosis of hearing deficit we found that the highest agreement rate
      was observed in children with sensorineural hearing loss (p < 0.01). CONCLUSIONS:
      The prevalence of most risk factors of hearing deficit was similar in children
      with sensorineural, conductive and mixed type of hearing loss, only
      hyperbilirubinemia seemed to predispose to sensorineural hearing deficit and
      isolated craniofacial malformations seemed to be associated with conductive
      hearing loss. Sensorineural hearing deficit usually occurred bilaterally and was
      severe or profound, while conductive and mixed type of hearing deficit were most
      often of mild degree. Most children with the final diagnosis of sensorineural
      hearing deficit had positive result of hearing screening by means of otoacoustic
      emissions.

PMID- 29447812
TI  - Total serum bilirubin levels and sensorineural hearing loss in the US
      adolescents: NHANES 2007-2010.
AB  - OBJECTIVE: We aimed to investigate whether current levels of total serum
      bilirubin are associated with different subtypes of sensorineural hearing loss
      (SNHL) in adolescents. METHODS: A set of cross-sectional data from the National
      Health and Nutrition Examination Survey (NHANES) (2007-2010) was used. A subset
      of 1404 adolescents was sampled for measurements of total serum bilirubin,
      tympanometry, and average pure tone threshold at low-frequencies (LPTA: 500,
      1000, 2000 Hz) or high-frequencies (HPTA: 3000, 4000, 6000, and 8000 Hz). SNHL
      was defined as the hearing loss that had type A tympanograms with a peak
      admittance of 0.3 ml or greater. Associations between serum bilirubin (square
      root transformed) and different subtypes of SNHL were evaluated using binary or
      multinomial logistic regression models with 4-year sampling weights. The
      bootstrap method was used for estimation of variance and 10-fold cross-validation
      for assessment of overfitting issue. RESULTS: Total serum bilirubin levels were
      found to be associated with any high-frequency (HPTA>15 dB in at least one ear,
      adjusted odds-ratio (ORa)(bootstrap 95% confidence interval) = 3.29(1.31-8.19), p
      = 0.011), but not with any low-frequency (LPTA>15 dB in at least one ear), SNHL
      in the US adolescents. Furthermore, high-frequency SNHL with HPTA>15 dB in both
      ears (bilateral) or HPTA>=25 dB in at least one ear, compared to that with
      HPTA>15 dB in one ear only (unilateral) or HPTA = 15-25 dB in at least one ear,
      had a stronger association with total serum bilirubin levels (ORa = 5.37(1.27
      22.65), p = 0.022 for bilateral; ORa = 2.64(0.84-8.25), p = 0.094 for unilateral;
      ORa = 5.00(0.95-26.58), p = 0.058 for HPTA>=25 dB in at least one ear; as well as
      ORa = 3.06(1.15-8.25), p = 0.025 for HPTA = 15-25 dB in at least one ear). No
      severe overfitting problems were found. CONCLUSION: Our findings suggest that
      current levels of total serum bilirubin may be informative in predicting and/or
      targeting high-frequency SNHL in the US adolescents.

PMID- 29447813
TI  - Long-term outcomes of Universiti Kebangsaan Malaysia Cochlear Implant Program
      among pediatric implantees.
AB  - OBJECTIVES: Cochlear implant (CI) greatly enhances auditory performance as
      compared to hearing aids and has dramatically affected the educational and
      communication outcomes for profoundly deaf children. Universiti Kebangsaan
      Malaysia (UKM) pioneered CI program in 1995 in the South East Asia. We would like
      to report the long-term outcomes of UKM paediatric cochlear implantation in terms
      of: the proportion of children who were implanted and still using the device, the
      children's modes of communication, their educational placements, and their
      functional auditory/oral performance. We also examined the factors that affected
      the outcomes measured. STUDY DESIGN: This was a cross sectional observational
      study. METHODS: Two sets of questionnaires were given to 126 parents or primary
      caregivers of the implantees. The first set of questionnaire contained questions
      to assess the children's usage of CI, their types of education placement, and
      their modes of communication. The second set of questionnaire was the Parent's
      Evaluation Of Aural/Oral Performance of Children (PEACH) to evaluate the
      children's auditory functionality. RESULTS: Our study showed that among the
      implantees, 97.6% are still using their CI, 69.8% communicating orally, and 58.5%
      attending mainstream education. For implantees that use oral communication and
      attend mainstream education, their mean age of implantation is 38 months. This is
      significantly lower compared to the mean age of implantation of implantees that
      use non-oral communication and attend non-mainstream education. Simple logistic
      regression analysis shows age of implantation reliably predicts implantees (N =
      126) would communicate using oral communication with odds ratio of 0.974, and
      also predict mainstream education (N = 118) with odds ratio of 0.967. The median
      score of PEACH rating scale is 87.5% in quiet, and this significantly correlates
      with an earlier age of implantation (r = -0.235 p = 0.048). CONCLUSIONS: UKM
      Cochlear Implant Program has achieved reasonable success among the pediatric
      implantees, with better outcomes seen in those implanted at the age of less than
      4 years old.

PMID- 29447814
TI  - Spontaneous retropharyngeal and mediastinal thoracic duct cyst in an infant with
      respiratory distress.
AB  - Thoracic duct cysts (TDC) within the retropharyngeal space and mediastinum are
      exceedingly rare lesions, with the majority related to trauma or neoplasm. We
      describe a case of an otherwise healthy 8-month-old boy who presented with severe
      respiratory distress, which was found to be caused by a large, spontaneous TDC
      occupying most the retropharyngeal and mediastinal space. To our knowledge, this
      is the youngest patient to date presenting with TDC. Ultimately, his TDC was
      completely resolved with sclerotherapy, however the patient's age and size
      presented unique challenges to his medical management, which we describe below.

PMID- 29447815
TI  - Pre- and post-operative evaluation of the frequency of nocturnal enuresis and
      Modified Pediatric Epworth Scale in pediatric obstructive sleep apnea patients.
AB  - OBJECTIVE: To investigate the beneficial effect of adenotonsillectomy (AT) on
      nocturnal enuresis (NE) in children with adenotonsillar hypertrophy and evaluate
      the Modified Pediatric Epworth Scale (MPES). METHODS: This was a prospective
      study comparing preoperative and postoperative evaluation of the frequency of NE
      and MPES in pediatric obstructive sleep apnea (OSA). A questionnaire on NE
      history was prepared based on the Turkish Enuresis Guidelines. NE histories were
      evaluated pre- and postoperatively on the first month and third month,
      respectively. MPES questions were asked to the parents of all the OSA patients
      pre- and postoperatively, and scores were noted. RESULTS: Eighty-four (84)
      pediatric OSA patients were involved in the study. Preoperatively, 19 patients
      (27%) complained about nocturnal enuresis. After the surgery, 52% of the patients
      with NE had complete resolution of NE (p < 0.001). Postoperatively, the average
      Epworth scores of both groups significantly decreased (p < 0.001). CONCLUSION:
      There is a strong correlation between OSA and NE. In the present study, enuresis
      in pediatric OSA patients significantly decreased after surgery. Also, Epworth
      scores decreased significantly after surgery. In children with nocturnal
      enuresis, the presence of OSA symptoms should be questioned.

PMID- 29447816
TI  - Cochlear implant symmetry via template.
AB  - Current trends in bilateral cochlear implantation (CI) favor a minimally invasive
      subperiosteal pocket technique. Symmetric receiver-stimulator (R/S) placement is
      an important goal for bilateral CI, especially with regard to patient
      satisfaction. In this article, we describe a method easily adopted to achieve
      optimal symmetry. Upon reviewing the Senior Author's 11 bilateral CI cases using
      the direct subperiosteal pocket technique with the proposed "mirror template," we
      found improved symmetry, which translated into high patient and family
      satisfaction regarding the aesthetics of the symmetric R/S placement.

PMID- 29447817
TI  - Mature and immature pediatric head and neck teratomas: A 15-year review at a
      large tertiary center.
AB  - INTRODUCTION: Pediatric head and neck teratomas account for less than 4% of
      congenital teratomas. The distinct presentations and outcomes of mature and
      immature head and neck teratomas have not been well established. OBJECTIVES: To
      review the management and outcomes of pediatric head and neck teratomas. To
      distinguish differences between mature and immature tumors with respect to the
      age at presentation and surgery, tumor size and location, alpha fetoprotein (AFP)
      levels, airway management, and recurrence. METHODS: A 15-year retrospective chart
      review of patients treated for head and neck teratomas at Texas Children's
      Hospital was performed. A total of 20 patients were included. Wilcoxon rank and
      Fisher's exact tests were used for statistical analysis. RESULTS: Immature
      teratomas were associated with both higher AFP levels (80800 ng/ml, p = 0.02) and
      maximum tumor dimensions (14.4 cm, p = 0.0034) than mature teratomas (24400 ng/ml
      and 6.44 cm). Patients with immature tumors were younger at the time of surgical
      resection (19.8 days, p = 0.025) compared to those with mature tumors (348 days).
      89% of immature teratomas involved anterior neck localization compared to 27% for
      mature teratomas (p = 0.0098); 88% of the immature teratomas required an EXIT (Ex
      Utero Intrapartum Treatment) procedure compared with 40% of the mature teratomas
      (p = 0.0656). Recurrence was noted in only two cases: an immature teratoma 51
      months after incomplete resection and a mature teratoma 33 months after complete
      resection. Long-term consequences of surgical resection included cleft palate
      (38.9%), dysphagia (33.3%), facial nerve paresis/paralysis (16.7%) and
      tracheotomy (16.7%). CONCLUSION: Immature teratomas had higher AFP levels, tumor
      dimensions, frequency of anterior neck localization, and requirement of EXIT than
      mature teratomas. Given that there was no significant difference between the
      recurrence rates of immature and mature teratomas, follow-up vigilance should be
      maintained equally regardless of tumor maturity.

PMID- 29447818
TI  - Sirolimus for management of complex vascular anomalies - A proposed dosing
      regimen for very young infants.
AB  - Neonates with vascular anomalies causing airway compromise and other
      complications require early initiation of medical therapy. Sirolimus has emerged
      as a safe and effective treatment, but standard recommendations for dosing start
      at seven months. Guidelines are needed for dosing in very young infants, who have
      reduced hepatic metabolism of sirolimus. We present our experience treating six
      neonates (mean age 14.8 days) with complicated vascular anomalies. Standard
      dosing caused supratherapeutic levels in this population. Our modified dosing
      regimen has resulted in safe therapeutic concentrations. Properly dosed,
      sirolimus is a viable and potentially lifesaving option for neonates with severe
      morbidity from vascular anomalies.

PMID- 29447819
TI  - Lingual tonsillectomy in children with Down syndrome: Is it safe?
AB  - OBJECTIVE: Evaluate peri-operative course and morbidity in children with Down
      syndrome (DS) who underwent a lingual tonsillectomy (LT) for residual obstructive
      sleep apnea (rOSA). METHODS: Retrospective case series for children with DS who
      underwent LT for rOSA from April 2011 to July 2016. Our primary outcomes were
      length of stay, readmission and complications. Surgical effectiveness was
      evaluated by change in the obstructive apnea-hypopnea-index(OAHI) and oxygen
      saturation nadir. RESULTS: Thirty-nine patients underwent LT. The mean length of
      stay was 1.3 days with n = 21(72%) staying one night. One subject (2.6%) had a
      post-operative bleed that did not require operative intervention. No other major
      complications occurred. In terms of effectiveness of surgery, twenty-nine
      children had sufficient data for inclusion. Median OAHI did not appreciably
      change (p = 0.07) from before surgery. Five subjects (17%) were cured of OSA
      (OAHI < 2/hour) and a mix of improvement and worsening was identified. The lowest
      oxygen saturation improved from 78% (SD = 7) before surgery to 82% (SD = 6) after
      surgery (p = 0.003). CONCLUSION: LT has a favorable post-operative course but its
      effectiveness at curing rOSA in the DS population has not been
      established/proven. Further research is indicated to determine optimal surgical
      management for DS children with LTH. LEVEL OF EVIDENCE: 4.

PMID- 29447820
TI  - How does a bilingual environment affect the results in children with cochlear
      implants compared to monolingual-matched children? An Italian follow-up study.
AB  - OBJECTIVES: To compare the results after cochlear implantation achieved by
      monolingual and bilingual deaf children implanted at our Institution, with the
      aim of understanding if there are any differences between the two groups and if
      there is a correlation between the outcomes and some patients' variables.
      METHODS: The study group was composed by 14 bilingual deaf children and the
      control group by the same number of monolingual children implanted at our
      Institution. The control group was obtained by matching to each bilingual child a
      monolingual one with a similar clinical history regarding age at hearing loss
      diagnosis, age at first hearing-aids fitting and age at CI procedure. Children
      received a speech perception and linguistic development evaluation through
      specific structured tests. The linguistic competence of the patients both in
      mainstream and native language was determined by the Student Oral Language
      Observation Matrix (SOLOM). RESULTS: We did not find any statistically
      significant differences between bilingual and monolingual children in speech
      perception outcomes. Nevertheless, we obtained different results concerning
      language skills: bilingual implanted children scored lower at structured language
      tests, even if the difference was not statistically relevant. Bilingual children
      scored significantly lower than monolingual ones at the SOLOM scale for
      linguistic competence. CONCLUSION: The results reported in the present study show
      better language skills after cochlear implant in Italian monolingual cases than
      in bilingual ones. This seems to be related to the condition of bilingualism in
      Italy, mainly related to immigration, and frequently associated with low socio
      economic levels, poor competence in the mainstream language and poor social
      integration, with a suboptimal exposure to the mainstream language and
      difficulties in following the rehabilitative program.

PMID- 29447821
TI  - Genetic analysis of CLDN14 in the Chinese population affected with non-syndromic
      hearing loss.
AB  - OBJECTIVE: The CLDN14 gene, encoding the tight junction protein Claudin-14, has
      been proposed as a candidate causative gene affecting autosomal recessive non
      syndromic hearing loss (ARNSHL). Genetic analysis of nonsynonymous single
      nucleotide variations (nsSNVs) in CLDN14 has been performed in different
      populations. The role of CLDN14 nsSNVs in contributing to hearing loss in Chinese
      populations would be investigated in this study. METHODS: Target screening for
      CLDN14 variations were conducted in 500 unrelated patients diagnosed with non
      syndromic hearing loss (NSHL). RESULTS: No reported pathogenic CLDN14 nsSNVs in
      heterozygote or homozygote were detected in this study, however, we identified 4
      heterozygous nsSNVs [c.11C > T, p.(Thr4Met); c.16G > A, p.(Val6Met); c.68T > C,
      p.(Ile23Thr); c.367A > C, p.(Thr123Pro)] in CLDN14. The 4 nsSNVs are located at
      claudin-14 transmembrane domains, but assessed to be poorly conservative and non
      pathogenic via multiple in silico algorithms. The structure-based analysis also
      suggested that the 4 nsSNVs had less structural and functional impact on claudin
      14. CONCLUSION: Our findings indicated that CLDN14 might not be a major causative
      gene for NSHL in Chinese populations, which would contribute to fully
      understanding the genetic cause of NSHL in the East Asian populations.

PMID- 29447822
TI  - Are validated patient-reported outcomes used on children in pediatric
      otolaryngology? A systematic review.
AB  - OBJECTIVES: Review the pediatric otolaryngology literature to 1) identify studies
      in which children completed patient-reported outcome (PRO) measures and 2)
      appraise the psychometric quality and validity of these PROs as they apply to
      pediatrics. METHODS: In October 2016, a systematic review was performed by two
      reviewers on PubMed/MEDLINE and EMBASE for all otolaryngology-related studies
      that utilized PROs in children. Inclusion criteria included articles that
      required children (age<18) to complete PROs. Exclusion criteria included
      validation studies, reviews, and abstracts. Interreviewer agreement was
      determined using Cohen's kappa. Quality and rigor of validation testing for
      included PROs was determined using the COnsensus-based Standards for selection of
      health status Measurement Instruments. RESULTS: Interrater agreement was very
      good (kappa = 0.91; 95% CI, 0.85-0.98). Out of 316 articles retrieved, 11 met
      inclusion criteria. Eight PROs were identified. Six PROs were tested for validity
      and three of these PROs were tested for validity specifically within children.
      The most frequently utilized PRO was the Pediatric Rhinoconjunctivitis Quality of
      Life Questionnaire. Two studies (18.2%) utilized PROs within the scope of their
      validation. Seven studies (63.6%) used PROs outside the scope of their
      validation. Two studies (18.2%) used non-validated PROs. CONCLUSIONS: Patient
      reported outcomes have become an integral part of research and quality
      improvement. There is a relative paucity of PROs directed towards children in
      pediatric otolaryngology and some studies utilized PROs that were not validated
      or not validated for use in this age group. Future efforts to design and validate
      more instruments may be warranted.

PMID- 29447823
TI  - EXIT (ex utero intrapartum treatment) in a growth restricted fetus with tracheal
      atresia.
AB  - Congenital high airway obstruction syndrome (CHAOS) encompasses a heterogeneous
      group of pathologies leading to poor lung development and difficulty oxygenating
      the newborn after delivery. While previously uniformly fatal, the ex utero
      intrapartum therapy (EXIT) procedure has provided a method to treat these
      patients and provide an airway to potentiate survival. We present a patient
      diagnosed prenatally with CHAOS secondary to tracheal atresia complicated by
      severe intra-uterine growth restriction (IUGR) who was successfully delivered via
      an EXIT procedure at 33-weeks. Multidisciplinary care and planning is paramount.

PMID- 29447824
TI  - Central xanthoma of the mandible associated with hyperlipidemia: A rare
      presentation.
AB  - Xanthoma is a common, self-limiting cutaneous lesion of non-Langerhans cell,
      lipid-laden foamy histiocytes that is often concomitant with hyperlipidemia. The
      intraosseous counterpart is rarely encountered and typically presents as a
      painless, expansile osteolytic process in the context of hyperlipidemia or
      normolipidemia. Only a scant number of gnathic xanthomas have been reported in
      the otolaryngologic literature. We report the clinical, laboratory, radiographic,
      histopathologic, immunohistochemical, and ultrastructural studies of a mandibular
      lesion discovered in an asymptomatic 16-year-old male, and associated with 2
      previously unreported comorbidities, namely hyperlipidemia and vitamin D
      deficiency.

PMID- 29447825
TI  - Profilactic role of simvastatin and mitomycin C in tracheal stenosis after
      tracheal damage: Study in rats.
AB  - OBJECTIVES: We aimed to investigate the prophylactic effect simvastatin of and
      mitomycin C (MMC) on laryngeal and tracheal stenosis in tracheotomised rats by
      histopathological evaluation of laryngotracheal segment. Randomized prospective
      single-blind. MATERIAL AND METHOD: Standard vertical tracheotomy was performed on
      24 rats. Then the animals were randomly divided into three groups as A, B and C.
      In group A 0.4 mg/day once daily mitomycin C was injected to the paratracheal
      region for 14 days. In group B daily 30 mg/kg/day simvastatin was given via
      gavage to rats for 14 days. In group C 2 cc/day intraperitoneal saline given to
      rats and the created control group by 14 days follow up. After 10 days, tracheal
      cannulas were removed. Three weeks later, all animals were euthanized and trachea
      specimens were harvested. The present study investigates the effects of MMC and
      Simvastatin on fibrosis, inflammation, stenosis index and tracheal wall thickness
      in a tracheal injury model. RESULTS: The difference between the groups in terms
      of degree of inflammation scores was statistically insignificant (P = 0,187).
      Differences between the groups were found to be insignificant in terms of the
      preventionof fibrosis (P = 0,993). There was no significant difference between
      groups in terms of stenosis index (P = 0.645). In terms of wall thickness,
      control, simvastatin and mitomycin C groups were statistically different (p =
      0.038). The difference between post-hoc test results was between Mitomycin C and
      control groups (p = 0.036). Maximum wall thickness in the MMC group (0,299 mm)
      was significantly lower compared to the control group (0,382 mm)(P < 0,0001).
      Maximum wall thickness was statistically lower in the simvastatin (0.324 mm)
      group compared with the control group (0.382 mm) (P < 0.0001). There was no
      statistically significant difference between the simvastatin group (0,198 mm) and
      control group (0,200 mm) with respect to minimum wall thickness (P = 0.982).
      Minimum wall thickness was significantly lower in the mitomycin-C group (0,160
      mm) comparison to the control group (0,200 mm) (P < 0.0001). CONCLUSION: It was
      detected that the simvastatin and MMC is not effective in preventing the tracheal
      stenosis, inflammation and fibrosis formation.

PMID- 29447826
TI  - Impact of age on the anatomy of the pediatric pterygopalatine fossa and its
      relationship to the suprazygomatic maxillary nerve block.
AB  - OBJECTIVES: The suprazygomatic maxillary nerve block is associated with improved
      post-operative pain management after select craniofacial surgical procedures.
      This study's objective is to better define the impact of pediatric facial
      skeletal growth on techniques for accessing the pterygopalatine fossa (PPF).
      METHODS: Pediatric patients with prior thin-slice maxillofacial computed
      tomography imaging were identified in an institutional radiology database.
      Aquarius image-processing software (Ver. 4.4.11, TeraRecon, Inc., Foster City,
      CA) was used to measure from the suprazygomatic skin to the greater wing of the
      sphenoid where the needle is then re-oriented in an anterior and inferior
      trajectory allowing it to advance into the PPF. RESULTS: A total of 90 patients
      ranging from 0 to <=18 years of age were included in the study. The mean distance
      from the suprazygomatic skin to the foramen rotundum in patients 0 to <=12 months
      of age and >13 to <=18 years of age was 38.6 (SD +/- 4.7) and 47.1 (SD +/- 3.2)
      mm, respectively (p < .0001). The statistical analysis demonstrated a positive
      correlation between age in years and all of the measured distances (p = .0001).
      With respect to the plane of the needle entry site, the anterior and inferior
      angles required for passage into the PPF in the 0 to <=12 months age group were
      11 (SD +/- 2.1) and 9.0 (SD +/- 2.5) degrees, respectively, compared to those in
      the >13 to <=18 years of age group at 12.4 (SD +/- 1.9) and 12.1 (SD +/- 3.2)
      degrees, respectively. These data reveal that patients in the oldest compared to
      the youngest pediatric age groups require significantly greater needle insertion,
      yet the angles of needle re-orientation are clinically similar between these two
      pediatric age groups varying by up to only 3 degrees . CONCLUSION: As expected,
      the distance from the skin to the foramen rotundum increases significantly with
      age; however, the angles of re-orientation with respect to the original needle
      entry site demonstrated up to only 3 degrees  of variability between the youngest
      and oldest age groups evaluated in this pediatric cohort.

PMID- 29447827
TI  - A novel approach for comparing patterns of foreign body injuries across
      countries: A case study comparing European Countries and Bosnia and Herzegovina.
AB  - OBJECTIVES: The present study aimed at analyzing the characteristics of FB
      injuries from Bosnia and Herzegovina (B&H), a rapidly growing newly
      industrialized country, and to compare them with cases from European countries.
      METHODS: The analysis is based on FB injury cases included in the Susy Safe
      registry. Cases from the Ear-Nose-Throat (ENT) Clinic, University Clinical Center
      of Tuzla (B&H) were compared with cases from European countries participating in
      the Susy Safe project. Multiple Correspondence Analysis (MCA) was performed to
      elucidate differences within a large data set regarding mechanisms and objects
      causing injuries. RESULTS: The results of the MCA showed that the first three
      dimensions explained 43% of the variability. The first dimension was identified
      by children hospitalized for FB ingestion, the second one by children
      hospitalized for FB aspiration (lower airways), and the third one by children
      with an FB in the ear or in the upper airways. The analysis of the median of
      coordinates of factors contributing to each dimension showed that the greatest
      difference between B&H and European countries regarded the third one. Looking at
      the profile of these patients, it might be suggested that the proportion of males
      and females and the type of activity in which they were involved at time of
      injury occurrence are different among the countries considered CONCLUSIONS: This
      study proposes a simple tool for assessing differences among countries in the
      distribution of FB injuries. This case study shows that B&H has different
      patterns of FB injuries in the upper respiratory tract.

PMID- 29447828
TI  - Validity of automated threshold audiometry in school aged children.
AB  - BACKGROUND: Automated hearing tests have the potential to reduce the burden of
      disease amongst learners by introducing such services within the school context.
      METHODS: The aim of the study was to conduct a validation study on normal and
      hearing impaired learners, comparing air and bone conduction automated test
      results to conventional test results in 50 school aged learners (n = 100 ears)
      within a noise controlled school environment using a cross sectional comparative
      study design. The KuduWave 5000 (Emoyo.net) was used in this study. DATA
      ANALYSIS: The spearman's correlation coefficient was calculated to determine test
      retest reliability. The mean and standard deviation (SD) was measured for each
      frequency. The absolute mean difference (AMD) and SD was calculated for both air
      and bone conduction testing at each frequency for automated testing. A paired
      sampled t-test and a one way ANOVA was used to identify any significant
      differences. Alpha was set as 0.05. RESULTS: There was significant correlation
      between thresholds obtained for automated test one and test two for normal
      hearing and hearing impaired group. The spearmans correlation coefficient was
      high (close to +1) for majority of the results for both groups across the
      frequency range. Both air and bone conduction testing across the frequency range
      of 250 Hz-2000 Hz and at 8000 Hz were not statistically signfiicant (p < .005)
      for both groups, however at 4000 Hz for bone conduction testing in the hearing
      impaired group, there was a statisticially signficant difference (p = .003). This
      was attirubted to the variaibilty in bone conduction test results often due to
      force and placement of the bone vibrator. CONCLUSION: The findings indicate that
      automated audiometry can yield relaible results that are comparable to
      conventional test results. Key clinical considerations include extending the
      response time, regular rest periods, improving instructions and comfort levels.

PMID- 29447829
TI  - Custom-Made Titanium Miniplates Associated With Ultrahigh-Molecular-Weight
      Polyethylene Graft in Orthognathic Surgery: An Adjunct to Maxillary Advancement.
AB  - Patients with considerable maxillomandibular anteroposterior discrepancies and
      maxillary hypoplasia require corrective treatment through orthognathic surgery.
      However, in the treatment of severe maxillary retrognathism, it is necessary to
      reconstruct areas of bone deficiency through grafting techniques in addition to
      maxillary advancement using only the Le Fort I osteotomy. Treatment in these
      patients is more challenging and requires high surgical predictability.
      Alloplastic materials often have been used for the reconstruction of poor bone
      contours. Ultrahigh-molecular-weight polyethylene (UHMWPE) is currently an
      excellent filler material for poor bone regions and is a good substitute for
      autografts and other alloplastic materials for its unique properties, including
      high biocompatibility. Insertion of this material in the fixation system
      customized for virtually planned orthognathic surgeries is an innovative
      technique. This report describes the insertion of UHMWPE into custom-made
      titanium miniplates manufactured by computer-aided design and computer-aided
      manufacturing technology for orthognathic surgery consisting of maxillary
      advancement and mandibular retrusion to treat a patient with Crouzon syndrome,
      Class III malocclusion, and severe maxillary retrognathism.

PMID- 29447830
TI  - Syngnathia-Congenital Maxillomandibular fusion: Case Report and Literature
      Review.
AB  - Congenital maxillomandibular fusion is a rare disorder of the craniofacial
      region. Maintenance of the airway and difficulty in feeding are the main concerns
      for such patients. We performed a PubMed search to identify reported cases of
      syngnathia. With reference to the site of fusion and corresponding anomalies, the
      available studies were reviewed. The maxillomandibular fusion can be anterior
      fusion, unilateral or bilateral fusion, and complete fusion. The condition can be
      an isolated problem or associated with a syndrome. The condition requires
      immediate attention because it can be fatal. A case of isolated unilateral
      syngnathia, with the detailed review of the published data, is reported.

PMID- 29447831
TI  - Rhabdomyolysis After Prolonged Surgery: Report of 2 Cases and Review of
      Literature.
AB  - Rhabdomyolysis is a condition in which damaged muscle tissue breaks down and
      intracellular contents, including myoglobin, are released into the circulation.
      This produces a nonspecific clinical syndrome including electrolyte disturbances,
      hypovolemia, metabolic acidosis, coagulopathies, and risk of acute kidney injury.
      Rhabdomyolysis has been reported as a complication of prolonged surgical
      procedures but has rarely been reported in the oral and maxillofacial surgery
      literature. Early diagnosis and treatment of rhabdomyolysis are important to
      avoid long-term complications such as renal failure. We present 2 cases of
      postoperative rhabdomyolysis after prolonged maxillofacial surgical procedures in
      which the patients were managed without long-term sequelae. The pathophysiology,
      risk factors, diagnosis, and treatment of postoperative rhabdomyolysis are
      discussed, with a brief review of the literature.

PMID- 29447832
TI  - Involvement of maternal grandmother and teenage mother in intervention to reduce
      pacifier use: a randomized clinical trial.
AB  - OBJECTIVE: To assess the impact of an intervention for teenage mothers with the
      involvement of maternal grandmothers on the prevalence of pacifier use in the
      first six months of life. METHODS: This randomized clinical trial involved 323
      teenage mothers, allocated to four groups: intervention with teenagers only,
      intervention with teenagers and their mothers, and respective controls. Six
      breastfeeding counseling sessions, including the recommendation to avoid the use
      of a pacifier, were delivered at the maternity ward and subsequently at the
      teenagers' homes, at seven, 15, 30, 60, and 120 days postpartum. Data on infant
      feeding and pacifier use were collected monthly by interviewers blinded to group
      allocation. The impact of the intervention was measured by comparing survival
      curves for pacifier use in the first six months of life and mean time to pacifier
      introduction. RESULTS: The intervention had a significant impact on reducing
      pacifier use only in the group in which grandmothers were involved. In this
      group, the intervention delayed by 64 days the introduction of a pacifier (21-85
      days), compared to 25 days in the group without the participation of grandmothers
      (65-90 days). CONCLUSIONS: The intervention reduced pacifier use in the first six
      months of life and delayed its introduction until beyond the first month when
      grandmothers were involved. The intervention did not have a significant impact
      when only teenage mothers were involved.

PMID- 29447833
TI  - Editorial Comment.

PMID- 29447834
TI  - Reply by Authors.

PMID- 29447835
TI  - Clay eating attenuates lithium-based taste aversion learning in rats: A remedial
      effect of kaolin on nausea.
AB  - Kaolin clay eating has been considered as a marker of nausea in rats, because a
      variety of treatments, which evoke nausea in humans, generate consumption of
      kaolin clay in rats. The present study with two experiments replicated kaolin
      clay ingestion induced by an injection of emetic lithium chloride (LiCl). The
      LiCl injection, however, did not generate eating of wooden objects in rats. The
      present study also provides a new finding that consumption of kaolin clay
      alleviates rats' taste aversion learning caused by an LiCl injection. This
      finding is congruent with the contention that consumption of kaolin clay is not
      only a useful index of, but also an effective remedy for, drug-induced nausea in
      rats.

PMID- 29447836
TI  - Sensory denervation of inguinal white fat modifies sympathetic outflow to white
      and brown fat in Siberian hamsters.
AB  - White adipose tissue (WAT) and brown adipose tissue (BAT) have sympathetic
      nervous system (SNS) and sensory innervations. Previous studies from our
      laboratory revealed central neuroanatomical evidence of WAT sensory and BAT SNS
      crosstalk with double labeling of inguinal WAT (IWAT) sensory and interscapular
      BAT (IBAT) SNS neurons. We previously demonstrated that WAT lipolysis increases
      IBAT temperature, but this effect is absent when IWAT afferents are surgically
      denervated, which severs both sensory and SNS nerves. It is possible that WAT
      sensory feedback can regulate SNS drive to itself and other WAT and BAT depots,
      and thus contribute to the existence of differential SNS outflow to fat during
      different energy challenges. Here we selectively denervated IWAT sensory nerves
      in Siberian hamsters using capsaicin and measured norepinephrine turnover (NETO)
      i.e., SNS drive to WAT and BAT depots, IBAT uncoupling protein 1 (UCP1)
      expression, body mass, fat mass, blood glucose, and food consumed after a 24-h
      cold exposure. IWAT sensory denervation decreased both IWAT and IBAT NETO and
      IBAT UCP1 expression. IWAT sensory denervation, however, increased mesenteric WAT
      (MWAT) NETO after the 24-h cold exposure and did not modify epididymal WAT (EWAT)
      and retroperitoneal WAT (RWAT) NETO compared with respective controls. Body mass,
      fat mass, blood glucose, and food consumed were unchanged across groups. RWAT and
      EWAT mass decreased in capsaicin-injected hamsters, but did not in the vehicle
      hamsters. These results functionally demonstrate the existence of IWAT sensory
      and IBAT SNS crosstalk and that a disruption in this sensory-SNS feedback
      mechanism modifies SNS drive to IWAT, IBAT, and MWAT, but not EWAT and RWAT.

PMID- 29447837
TI  - Analyses of the molecular mechanisms associated with salinity adaption of
      Trachidermus fasciatus through combined iTRAQ-based proteomics and RNA sequencing
      based transcriptomics.
AB  - Osmoregulation mechanism underlying acclimation and adaptation of migratory fish
      to different salinities has been studied for decades. Recently developed
      transcriptomic and proteomic techniques would make it possible to provide more
      reliable data to decipher the mechanism study at a molecular level. Here in this
      study, an integrative analysis of the kidney-specific transcriptome and proteome
      was performed to identify important regulators and pathways involved in salinity
      adaption of roughskin sculpin (Trachidermus fasciatus). Fish were subjected to
      seawater-to-freshwater transfer that was achieved in 24 h, samples were collected
      at 12, 24 and 48 h after the start of the experiment. Time course profiling of
      gene and protein expressions were examined using RNA-seq and iTRAQ methods. A
      total of 1504 differentially expressed genes (DEGs) and 378 differentially
      expressed proteins (DEPs) were identified at the three time points. 66 proteins
      were filtered by correlation of transcriptome and proteome results. When
      comparing the data obtained from the three time points, 12 h exhibited the
      largest number of DEGs and DEPs, suggesting the time course experiment is
      critical to clarify the framework of regulatory genes/proteins in response to
      salinity change. This study provides the first time-course, kidney-specific,
      combined transcriptomic and proteomic profiling associated with salinity adaption
      of Trachidermus fasciatus. The results revealed the possibility of T. fasciatus
      as an experimental animal for osmoregulation studies, showed the powerfulness of
      combining transcriptomic and proteomic approaches to provide molecular insights
      of osmoregulation mechanisms in migratory fish.

PMID- 29447838
TI  - Authors' Response.

PMID- 29447840
TI  - Microbial dormancy and boom-and-bust population dynamics under starvation stress.
AB  - We propose a model for the growth of microbial populations in the presence of a
      rate-limiting nutrient which accounts for the switching of cells to a dormant
      phase at low densities in response to decreasing concentration of a putative
      biochemical signal. We then show that in conditions of nutrient starvation, self
      sustained oscillations can occur, thus providing a natural explanation for such
      phenomena as plankton blooms. However, unlike results of previous studies, the
      microbial population minima do not become unrealistically small, being buffered
      during minima by an increased dormant phase population. We also show that this
      allows microbes to survive in extreme environments for very long periods,
      consistent with observation. The mechanism provides a natural vehicle for other
      such sporadic outbreaks, such as viral epidemics.

PMID- 29447839
TI  - Consensus statement on the need for innovation, transition and implementation of
      developmental neurotoxicity (DNT) testing for regulatory purposes.
AB  - This consensus statement voices the agreement of scientific stakeholders from
      regulatory agencies, academia and industry that a new framework needs adopting
      for assessment of chemicals with the potential to disrupt brain development. An
      increased prevalence of neurodevelopmental disorders in children has been
      observed that cannot solely be explained by genetics and recently pre- and
      postnatal exposure to environmental chemicals has been suspected as a causal
      factor. There is only very limited information on neurodevelopmental toxicity,
      leaving thousands of chemicals, that are present in the environment, with high
      uncertainty concerning their developmental neurotoxicity (DNT) potential. Closing
      this data gap with the current test guideline approach is not feasible, because
      the in vivo bioassays are far too resource-intensive concerning time, money and
      number of animals. A variety of in vitro methods are now available, that have the
      potential to close this data gap by permitting mode-of-action-based DNT testing
      employing human stem cells-derived neuronal/glial models. In vitro DNT data
      together with in silico approaches will in the future allow development of
      predictive models for DNT effects. The ultimate application goals of these new
      approach methods for DNT testing are their usage for different regulatory
      purposes.

PMID- 29447841
TI  - CRISPR/Cas9 generated human CD46, CD55 and CD59 knockout cell lines as a tool for
      complement research.
AB  - BACKGROUND: To prevent unwanted complement activation and subsequent damage,
      complement activation must be tightly regulated on healthy host cells.
      Dysregulation of the complement system contributes to the pathology of diseases
      like Paroxysmal Nocturnal Hemoglobinuria and atypical Hemolytic Uremic Syndrome.
      To investigate complement regulator deficiencies, primary patient cells may be
      used, but access to patient cells may be limited and cells are heterogeneous
      between different patients. To inhibit regulator function on healthy host cells,
      blocking antibodies can be used, though it may be difficult to exclude antibody
      mediated effects. To circumvent these issues, we created single and combined
      complement regulator human knockout cells to be able to in vitro investigate
      complement activation and regulation on human cells. METHODS: CRISPR/Cas9 was
      used to knockout (KO) complement regulatory proteins CD46, CD55 and/or CD59 in
      human HAP1 cells. Single cell derived cell lines were profiled by Sanger
      sequencing and flow cytometry. To confirm the lack of complement regulatory
      function, the cells were exposed to complement in normal human serum and
      subsequently C3 and C4 deposition on the cell surface were detected by using flow
      cytometry. RESULTS: We created single KO cell lines that completely lacked CD46,
      CD55 or CD59. We additionally generated double CD46/CD55, CD46/CD59 and CD55/CD59
      KOs and triple CD46/CD55/CD59 KOs. Upon classical pathway activation, deletion of
      CD46 resulted in increased C3 and C4 deposition, while deleting CD55 mainly
      resulted to increased C3 deposition, confirming their reported function in
      complement regulation. Upon alternative pathway activation, C3 deposition was
      only observed on the triple CD46/CD55/CD59 KO cells and not on any of the other
      cell lines, suggesting that human cells are resistant to spontaneous complement
      activation and suggesting a role for CD59 in C3 regulation. CONCLUSIONS: The
      generation of complement regulator KO cell lines provides a relevant tool for
      future in vitro investigations of complement activation and regulation on human
      cells. Furthermore, these cell lines may also be helpful to evaluate therapeutic
      complement inhibitors and may shed light on novel roles of complement regulatory
      proteins as we here observed for CD59.

PMID- 29447843
TI  - Creativity and cognitive control: Behavioral and ERP evidence that divergent
      thinking, but not real-life creative achievement, relates to better cognitive
      control.
AB  - Two studies used event-related potentials (ERPs) to examine whether and how
      divergent thinking and creative achievement are linked to attentional flexibility
      and cognitive control as indexed by response times and by the amplitude of the
      anterior N2 ERP component. Both experiments used an oddball paradigm in which
      participants viewed hierarchical letter stimuli and identified target letters in
      frequent and rare target trials. The successful identification of targets
      required attentional flexibility when switching levels of attention (from the
      frequent global to the rare local attentional level, or vice-versa). Divergent
      thinkers showed smaller switching times on rare target trials, indicating higher
      levels of attentional flexibility. Furthermore, divergent thinkers engaged
      cognitive control processes more strongly at the moment of the attentional switch
      (and before the response), as indicated by a larger N2 difference between
      frequent and rare targets. In contrast, creative achievement was associated
      neither with the switching times on rare target trials, nor with a larger N2
      difference between frequent and rare targets. All results held when controlling
      for general intelligence. Results from these studies provide evidence that
      divergent thinking is associated with higher attentional flexibility and that
      such attentional flexibility relies on cognitive control processes required when
      disengaging from one level of attention (e.g., global), and shifting to the other
      level of attention (e.g., local).

PMID- 29447842
TI  - Neutrophils drive type I interferon production and autoantibodies in patients
      with Wiskott-Aldrich syndrome.
AB  - BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency
      caused by mutations in Wiskott-Aldrich syndrome protein (WASp), a key regulator
      of cytoskeletal dynamics in hematopoietic cells. A high proportion of patients
      experience autoimmunity caused by a breakdown in T- and B-cell tolerance.
      Moreover, excessive production of type I interferon (IFN-I) by plasmacytoid
      dendritic cells (pDCs) contributes to autoimmune signs; however, the factors that
      trigger excessive innate activation have not been defined. OBJECTIVE: Neutrophil
      extracellular traps (NETs) emerged as major initiating factors in patients with
      diseases such as systemic lupus erythematosus and rheumatoid arthritis. In this
      study we explored the possible involvement of aberrant neutrophil functions in
      patients with WAS. METHODS: We evaluated the expression of a set of granulocyte
      genes associated with NETs in a cohort of patients with WAS and the presence of
      NET inducers in sera. Using a mouse model of WAS, we analyzed NET release by WASp
      null neutrophils and evaluated the composition and homeostasis of neutrophils in
      vivo. By using depletion experiments, we assessed the effect of neutrophils in
      promoting inflammation and reactivity against autoantigens. RESULTS: Transcripts
      of genes encoding neutrophil enzymes and antimicrobial peptides were increased in
      granulocytes of patients with WAS, and serum-soluble factors triggered NET
      release. WASp-null neutrophils showed increased spontaneous NETosis, induced IFN
      I production by pDCs, and activated B cells through B-cell activating factor.
      Consistently, their depletion abolished constitutive pDC activation, normalized
      circulating IFN-I levels, and, importantly, abolished production of
      autoantibodies directed against double-stranded DNA, nucleosomes, and
      myeloperoxidase. CONCLUSIONS: These findings reveal that neutrophils are involved
      in the pathogenic loop that causes excessive activation of innate cells and
      autoreactive B cells, thus identifying novel mechanisms that contribute to the
      autoimmunity of WAS.

PMID- 29447844
TI  - Angiotensin II facilitates GABAergic neurotransmission at postsynaptic sites in
      rat amygdala neurons.
AB  - The central nucleus of the amygdala (CeA) is critical in the regulation of sodium
      appetite. Angiotensin II (Ang II) is important in the generation of sodium
      appetite and may function as a neurotransmitter or modulator to affect the
      synaptic transmission and the excitability of neurons. However, the role of Ang
      II in the CeA remains unclear. In this study, we determined the effects of Ang II
      on the excitatory and inhibitory synaptic inputs to the CeA neurons in brain
      slices with whole-cell patch-clamp recordings. Ang II (0.5-5 MUM) significantly
      potentiated the amplitude of spontaneous GABAergic inhibitory postsynaptic
      currents (IPSCs) in a concentration-dependent manner. Ang II (2 MUM)
      significantly increased the amplitude of miniature GABAergic inhibitory
      postsynaptic currents (mIPSCs) without affecting the frequency. This effect was
      blocked by Ang II type 1 (AT1) receptor antagonist, losartan. One mM guanosine 5'
      O-(-2-thiodiphosphate) (GDP-beta-s) in the pipette internal solution eliminated
      the facilitatory effect of Ang II on GABAergic synaptic transmission. In
      contrast, Ang II had no effect on the spontaneous glutamatergic excitatory
      postsynaptic currents (EPSCs) and did not alter the frequency and amplitude of
      miniature EPSCs at concentrations that facilitated IPSCs. Furthermore, Ang II
      decreased the firing activity of CeA neurons, and this effect was abolished by
      losartan and GDP-beta-s. In addition, Ang II failed to inhibit CeA neurons in the
      presence of bicuculline. These data provide substantial new evidence that Ang II
      inhibits the CeA neurons by facilitation of GABAergic synaptic input efficacy
      through activation of postsynaptic AT1 receptors.

PMID- 29447846
TI  - Keeping cool: Kissing bugs avoid cannibalism by thermoregulating.
AB  - Kissing bugs possess a highly developed thermal sense and when starved, they
      attempt to bite any object which temperature is close to that of a warm-blooded
      host. At each feeding event, these insects take massive meals in just a few
      minutes. One could then expect fed-bugs being heated-up by the ingested warm
      blood and so becoming attractive to starved conspecifics. This is not however the
      case, arising the question about why cannibalism is very rare among these
      insects. Recently, the ability of thermoregulating during feeding has been
      demonstrated in Rhodnius prolixus. These bugs possess a countercurrent heat
      exchanger that cools down the ingested blood, before it reaches the abdomen. We
      hypothesise that avoiding thermal stress is not the only adaptive advantages of
      this mechanism, but could also help avoiding cannibalism. We tested this
      hypothesis by quantifying cannibalism by never-fed first-instar larvae on: (1)
      just-fed 5th instar bugs, (2) artificially heated just-fed bugs, (3) heated or
      (4) non-heated objects of the same size. In line with our hypothesis, non-heated
      just-fed bugs were not attacked by the 1st instar larvae, whereas heated bugs and
      object triggered biting behaviour in starved bugs, which performed either
      cleptohaematophagy or haemolymphagy on heated bugs. We conclude that cannibalism
      triggered by thermal stimuli has been one of the selection pressures that gave
      origin to thermoregulation during feeding on kissing bugs.

PMID- 29447845
TI  - Probing GABAA receptors with inhibitory neurosteroids.
AB  - gamma-aminobutyric acid type A receptors (GABAARs) are important components of
      the central nervous system and they are functionally tasked with controlling
      neuronal excitability. These receptors are subject to post-translational
      modification and also to modulation by endogenous regulators, such as the
      neurosteroids. These modulators can either potentiate or inhibit GABAAR function.
      Whilst the former class of neurosteroids are considered to bind to and act from
      the transmembrane domain of the receptor, the domains that are important for the
      inhibitory neurosteroids remain less clear. In this study, we systematically
      compare a panel of recombinant synaptic-type and extrasynaptic-type GABAARs
      expressed in heterologous cell systems for their sensitivity to inhibition by the
      classic inhibitory neurosteroid, pregnenolone sulphate. Generally, peak GABA
      current responses were inhibited less compared to steady-state currents,
      implicating the desensitised state in inhibition. Moreover, pregnenolone sulphate
      inhibition increased with GABA concentration, but showed minimal voltage
      dependence. There was no strong dependence of inhibition on receptor subunit
      composition, the exception being the rho1 receptor, which is markedly less
      sensitive. By using competition experiments with pregnenolone sulphate and the
      GABA channel blocker picrotoxinin, discrete binding sites are proposed.
      Furthermore, by assessing inhibition using site-directed mutagenesis and receptor
      chimeras comprising alpha, beta or gamma subunits with rho1 subunits, the
      receptor transmembrane domains are strongly implicated in mediating inhibition
      and most likely the binding location for pregnenolone sulphate in GABAARs. This
      article is part of the "Special Issue Dedicated to Norman G. Bowery".

PMID- 29447847
TI  - Perinatal selective serotonin reuptake inhibitor (SSRI) effects on body weight at
      birth and beyond: A review of animal and human studies.
AB  - The long-term impact of selective serotonin reuptake inhibitor (SSRI)
      antidepressant treatment during pregnancy and postpartum on offspring outcomes is
      still not clear. Specifically, perinatal SSRI exposure may have long-term
      consequences for body weight and related health outcomes in the newborn period
      and beyond. This review focuses on the impact of perinatal SSRI exposure on
      weight using human and animal findings. The impact of maternal mood is also
      explored. We propose potential mechanisms for weight changes, including how early
      alterations in serotonin signaling may have implications for weight via changes
      in metabolism and motor development. As the majority of serotonin is in the
      gastrointestinal (GI) system we also speculate that perinatal SSRI exposure might
      alter the brain-gut relationship, via the microbiome, leading to changes in
      feeding behavior and weight.

PMID- 29447848
TI  - Effects of tablet formulation and subsequent film coating on the supersaturated
      dissolution behavior of amorphous solid dispersions.
AB  - The effects of tablet preparation and subsequent film coating with amorphous
      solid dispersion (ASD) particles that were composed of a drug with poor water
      solubility and hydrophilic polymers were investigated. ASD particles were
      prepared with a drug and vinylpyrrolidone-vinyl acetate copolymer (PVPVA) or
      polyvinylpyrrolidone (PVP) at a weight ratio of 1:1 or 1:2 using a melt extrusion
      technique. Tablets were prepared by conventional direct compression followed by
      pan coating. A mathematical model based on the Noyes-Whitney equation assuming
      that stable crystals precipitated at the changeable surface area of the solid
      liquid interface used to estimate drug dissolution kinetics in a non-sink
      dissolution condition. All the ASD particles showed a maximum dissolution
      concentration approximately ten times higher than that of the crystalline drug.
      The ASD particles with PVPVA showed higher precipitation rate with lower polymer
      ratio, while PVP did not precipitate within 960 min regardless of the polymer
      ratio, suggesting the ASD particles of 1:1 drug:PVPVA (ASD-1) were the most
      unstable among the ASD particles considered. The dissolution of a core tablet
      with ASD-1 showed less supersaturation and a much higher precipitation rate than
      those of ASD-1 particles. However, a film-coated tablet or core tablet with a
      trace amount of hydroxypropylmethylcellulose (HPMC) showed a similar dissolution
      profile to that of the ASD-1 particles, indicating HPMC had a remarkable
      precipitation inhibition effect. Overall, these results suggest that tablet
      preparation with ASD may adversely affect the maintenance of supersaturation;
      however, this effect can be mitigated by adding an appropriate precipitation
      inhibitor to the formulation.

PMID- 29447849
TI  - Three-dimensional arterial spin labeling imaging with a DANTE preparation pulse.
AB  - On arterial spin-labeled (ASL) images, areas of bright intravascular signal will
      appear when the post labeling delay time is shorter than arterial transit time.
      Vascular suppression (VS) schemes reduce artefactual bright signal by dephasing
      intravascular labeled spins. However, existing VS methods, such as Motion
      Sensitized Driven-Equilibrium (MSDE), decrease the uniformity of the signal
      intensity distribution and extend the echo time. The purpose of this study is to
      compare VS using a Delays Alternating with Nutation for Tailored Excitation
      (DANTE) preparation pulse, with MSDE for ASL imaging on a flow phantom and
      volunteer data. In the phantom study, the signal decay pattern of moving water
      was similar for both methods. In the volunteer study, the bright intravascular
      signal artifact was decreased by both methods. However right-left differences in
      signal intensity were smaller using DANTE-prepared ASL. The proposed DANTE
      prepared ASL sequence has a vessel suppression effect while maintaining a uniform
      signal intensity distribution. This study indicates that DANTE is a potentially
      useful method for vessel suppression in ASL imaging.

PMID- 29447850
TI  - Impact of baseline CO2 on Blood-Oxygenation-Level-Dependent MRI measurements of
      cerebrovascular reactivity and task-evoked signal activation.
AB  - Neurovascular coupling describes the cascade between neuronal activity and
      subsequent Blood-Oxygenation-Level-Dependent (BOLD) signal increase. Based on
      this premise, the correlation of this BOLD signal increase with a particular
      task, such as finger-tapping, is used to map neuronal activation. This signal
      increase may be dampened in brain areas exhibiting impaired cerebrovascular
      reactivity (BOLD-CVR), leading to false negative activation. Blood-oxygenation
      level-dependent (BOLD) cerebrovascular reactivity (CVR) has also been used to
      optimize task evoked BOLD signal changes. To measure BOLD-CVR, controlled BOLD
      CVR studies have commonly been performed using a preset isocapnic carbon dioxide
      (CO2; ~40 mmHg) baseline, independent of subjects' resting CO2. This arbitrary
      baseline, however, may influence BOLD-CVR measurements. We therefore performed
      BOLD-CVR, as well as BOLD fMRI during a controlled bilateral finger-tapping task
      in two groups of ten subjects: group A at subject's resting CO2 and group B at a
      preset isocapnic CO2 baseline (40 mmHg). Whole brain BOLD-CVR was significantly
      decreased for group B (group A 0.26 (SD 0.05) vs group B 0.16 (SD 0.05), p <
      0.001). For the predefined hand area in the precentral cortex, BOLD-CVR and BOLD
      fMRI signal changes were significantly lower for group B (group A 0.20 (SD 0.04)
      vs group B 0.13 (SD 0.05), p < 0.01; 1.19 (SD 0.31) vs 0.62 (SD 0.37), p <
      0.01).CO2 levels significantly influence both BOLD-CVR and BOLD fMRI
      measurements. Hence, for an accurate interpretation, baseline CO2 levels and BOLD
      CVR should be considered complementary to task evoked BOLD fMRI.

PMID- 29447851
TI  - Advanced flow cytometry techniques for clinical detection.

PMID- 29447852
TI  - Loss of red opsin genes relaxes sexual isolation between skin-colour variants of
      medaka.
AB  - Colour vision is often essential for animals. Fine discrimination of colours
      enhances the ability of animals to find food, predators, or mating partners.
      Using two colour variants of medaka (Oryzias latipes), which mate assortatively
      depending on visual cues (pale grey versus dark orange), we recently established
      red colour-blind strains by knocking out the red opsin (long-wavelength
      sensitive) genes and elucidated that the fish were indeed insensitive to red
      light. In the present study, we investigated the mate choice of these red-blind
      fish. The colour variants with normal colour vision strongly preferred to mate
      with their own strain. The red-blind ones also preferred their own strain; i.e.
      they still mated assortatively. However, their preference was significantly
      weaker than that of fish with normal colour vision. In other words, the red-blind
      fish showed increased sexual interest in the other colour variant. These results
      indicated that reduced sensitivity to red light also reduced their ability to
      discriminate colours. This empirical evidence directly demonstrates that a change
      in cone-opsin repertoire changes mating decision behaviours, which would affect
      gene flow and speciation processes between conspecific colour variants in nature,
      as suggested in other studies.

PMID- 29447853
TI  - A comparator-hypothesis account of biased contingency detection.
AB  - Our ability to detect statistical dependencies between different events in the
      environment is strongly biased by the number of coincidences between them. Even
      when there is no true covariation between a cue and an outcome, if the marginal
      probability of either of them is high, people tend to perceive some degree of
      statistical contingency between both events. The present paper explores the
      ability of the Comparator Hypothesis to explain the general pattern of results
      observed in this literature. Our simulations show that this model can account for
      the biasing effects of the marginal probabilities of cues and outcomes.
      Furthermore, the overall fit of the Comparator Hypothesis to a sample of
      experimental conditions from previous studies is comparable to that of the
      popular Rescorla-Wagner model. These results should encourage researchers to
      further explore and put to the test the predictions of the Comparator Hypothesis
      in the domain of biased contingency detection.

PMID- 29447854
TI  - Risk factors and associated complications for postoperative urinary retention
      after lumbar surgery for lumbar spinal stenosis.
AB  - BACKGROUND CONTEXT: Postoperative urinary retention (POUR) is a very common
      postoperative complication of all surgeries (5%-70%) that may lead to
      complications such as urinary tract infection (UTI), bladder overdistension,
      autonomic dysregulation, and increased postoperative length of stay (LOS). Within
      the field of spine surgery, the reported incidence rate of POUR is highly
      variable (5.6%-38%). Lack of clear stratification of surgical level, spinal
      pathology, and inadequate sample size are major limitations of available studies
      concerning POUR following spine surgery, which may lead to inconsistency in the
      incidence of POUR and the ability to model its occurrence and consequences.
      PURPOSE: This study examines the incidence, predictive factors, and complications
      of POUR in patients undergoing elective posterior lumbar decompression with or
      without fusion for lumbar stenosis to eliminate bias from studying procedures
      done in different anatomical regions and with different approaches. Additionally,
      this study intends to identify the consequences of POUR. STUDY DESIGN AND
      SETTING: A retrospective consecutive cohort analysis was performed to examine
      patients undergoing posterior lumbar decompression who did and did not develop
      POUR. PATIENT SAMPLE: All patients undergoing posterior lumbar decompression with
      or without fusion for lumbar stenosis with claudication from January 2014 through
      December 2015 at our institution were evaluated. Patients under the age of 18 and
      patients with spinal malignancies or infections were excluded. OUTCOME MEASURES:
      Physiological measures included identification of POUR by evidence of reinsertion
      of a Foley catheter, use of straight catheterization postoperatively, or by a
      clear medical diagnosis with pharmacologic treatment. Other physiological
      measures included identification of development of UTI, sepsis, acute kidney
      injury (AKI), surgical site infection (SSI), or readmission within 90 days after
      surgery, as well as LOS and discharge disposition. METHODS: The electronic
      medical record was searched for all patients meeting inclusion and exclusion
      criteria. Postoperative urinary retention was defined as reinsertion of a Foley
      catheter, use of straight catheterization postoperatively, or a clear medical
      diagnosis with pharmacologic treatment. Statistical analysis was performed in R
      statistical software package version 3.3.2. Multiple variable selection
      techniques were used to determine appropriate variables for regression models,
      and logistic models were fit to the development of POUR and postoperative
      complications, whereas a linear regression model was used for LOS. RESULTS: Data
      were collected on 1,592 consecutive patients. Among the sample population, the
      mean age at surgery was 67 (standard deviation 10.1) and 45% of patients were
      women. The incidence rate of POUR was 17.1% (273/1592). Increased age (odds ratio
      [OR]=1.04; 95% confidence interval [CI], 1.02-1.06; p<.001), benign prostatic
      hyperplasia (BPH) (OR=1.92; 95% CI, 1.32-2.78); p<.001), previous AKI (OR=3.29;
      95% CI, 1.11-9.29; p=.025), and previous UTI (OR=1.69; 95% CI, 1.24-2.24; p<.001)
      significantly increased the probability of developing POUR. Factors including
      increased body mass index, coronary artery disease, congestive heart failure,
      diabetes mellitus, chronic obstructive pulmonary disease, tobacco use, and fusion
      were found to be non-significant and were excluded from the model. With respect
      to complications, POUR was found to be associated with development of UTI
      (OR=4.50; 95% CI, 3.14-6.45; p<.001), sepsis (OR=4.05; 95% CI, 1.16-13.55;
      p=.022), increased LOS (p<.001), increased likelihood to be discharged to a
      skilled nursing facility (SNF) (OR of discharge to home=0.44; 95% CI, 0.32-0.62;
      p<.001), and increased risk of readmission within 90 days of the index surgery
      (OR=1.60; 95% CI, 1.11-2.26; p=.009). Development of POUR did not increase the
      risk of developing AKI (OR=2.45; 95% CI, 0.93-6.30; p=.063) or a SSI (OR=1.09;
      95% CI, 0.56-2.02; p=.79). CONCLUSIONS: Overall, POUR was a significant risk
      factor for the development of UTI, sepsis, increased LOS, discharge to a SNF, and
      readmission within 90 days. Surgeons and anesthesiologists should take
      preventative measures against POUR in individuals with increased age, BPH, AKI,
      and UTI within 90 days before surgery, as these factors were found to
      significantly increase the risk of POUR.

PMID- 29447855
TI  - RPA using a multiplexed cartridge for low cost point of care diagnostics in the
      field.
AB  - A point of care device utilising Lab-on-a-Chip technologies that is applicable
      for biological pathogens was designed, fabricated and tested showing sample in to
      answer out capabilities. The purpose of the design was to develop a cartridge
      with the capability to perform nucleic acid extraction and purification from a
      sample using a chitosan membrane at an acidic pH. Waste was stored within the
      cartridge with the use of sodium polyacrylate to solidify or gelate the sample in
      a single chamber. Nucleic acid elution was conducted using the RPA amplification
      reagents (alkaline pH). Passive valves were used to regulate the fluid flow and a
      multiplexer was designed to distribute the fluid into six microchambers for
      amplification reactions. Cartridges were produced using soft lithography of
      silicone from 3D printed moulds, bonded to glass substrates. The isothermal
      technique, RPA is employed for amplification. This paper shows the results from
      two separate experiments: the first using the RPA control nucleic acid, the
      second showing successful amplification from Chlamydia Trachomatis. Endpoint
      analysis conducted for the RPA analysis was gel electrophoresis that showed 143
      base pair DNA was amplified successfully for positive samples whilst negative
      samples did not show amplification. End point analysis for Chlamydia Trachomatis
      samples was fluorescence detection that showed successful detection of 1 copy/MUL
      and 10 copies/MUL spiked in a MES buffer.

PMID- 29447856
TI  - Laparoscopic Sacrohysteropexy in a Woman at 12 Weeks' Gestation.
AB  - STUDY OBJECTIVE: To demonstrate laparoscopic sacrohysteropexy for a case of
      uterine prolapse in a 12 weeks, 3 days pregnant woman. To our knowledge this is
      the first case of laparoscopic sacrohysteropexy performed at 12 weeks of
      gestation to be reported in literature. DESIGN: A step-by-step explanation of the
      surgical procedure (Canadian Task Force classification III). SETTING: Maltepe
      University Hospital. PATIENT: A 37-year-old pregnant woman. INTERVENTION:
      Laparoscopic sacrohysteropexy. Institutional Review Board ruled that approval was
      not required for this study. MEASUREMENTS AND MAIN RESULTS: Uterine prolapse is
      very rare condition, manifesting in an estimated 10 000 to 15 000 pregnancies
      [1]. The management plan must be individualized, and the obstetrician should
      aware of possible complications, such as preterm labor, high incidence of
      abortion, cervical ulceration, and cervical dystocia. In general, bedrest, good
      genital hygiene, and pessary use is recommended. Alternatively, in cases where
      conservative solutions have failed, laparoscopic surgery in the pregnant patient
      may be considered. To date, only 1 case of laparoscopic promontohysteropexy at
      10th weeks of gestation was reported by Pirtea et al [2]. A 37-year-old woman, at
      12 weeks and 3 days of gestation, with stage III pelvic organ prolapse was
      referred to our clinic. Conservative management with pessary failed. The patient
      underwent laparoscopic sacrohysteropexy after written informed consent form was
      obtained. In exploration, uterine manipulation was difficult because of softness
      and large size of the uterus. First, the sigmoid colon was suspended at the
      abdominal wall to gain an adequate surgical field. The promontorium was dissected
      and the parietal peritoneum incised on the right pelvic side wall after ureter
      visualization. A polypropylene mesh was fixed to the cervix at the level of the
      uterosacral ligaments. The other edge of the mesh was fixed at the level of the
      promontory using the Uplift device (Neomedic International, Barcelona, Spain).
      Then, the peritoneum was sutured to cover the mesh. The patient was discharged 2
      days after surgery. At the examination the pelvic floor was detected to be
      normal. The patient delivered a healthy baby weighing 3030 g by cesarean section
      at 38 weeks of gestation. The position of the mesh was controlled during surgery.
      There was no peritoneal fold detected on the cervical part of mesh; however, no
      adhesion was observed. CONCLUSION: Laparoscopic sacrohysteropexy may be an
      alternative and safe approach, if conservative treatment fails, for pelvic organ
      prolapse during pregnancy.

PMID- 29447857
TI  - Estradiol effect on short-term object memory under hypocholinergic condition.
AB  - Estrogens positively affect object recognition memory (ORM). However, whether
      this effect rely on acetylcholine is unknown. Here we investigated if 17beta
      estradiol (E2) would be able to recover ORM deficits in animals with decreased
      expression of the Vesicular Acetylcholine Transporter (VAChT KDHET). We found
      that E2 improved short-term ORM (STM) in VAChT KDHET male and in OVX female
      mutant mice. However, E2 did not recover long-term (LTM) ORM in both sexes. Next,
      we tested whether hippocampal ERs activation could also rescue STM in mutant
      mice. Our results showed that ERalpha seems to be both sufficient and necessary
      for STM consolidation in female VAChT KDHET. Differently, in male, both ERalpha
      and ERbeta activation recovered STM. In addition, we tested whether mRNA level of
      estrogen receptors (ER) is also sensitive to VAChT expression. Female mutant mice
      showed lower levels of ER alpha (ERalpha) mRNA in the hippocampus, while no
      differences in male were observed. Together, our results showed that under
      hypocholinergic function, E2 improve short-term object recognition in both male
      and female. Furthermore, we showed that changes in VAChT expression might
      potentially modulate hippocampal ERalpha expression in a sex-dependent-manner.

PMID- 29447858
TI  - Intrathecal Injection of scAAV9-hIGF1 Prolongs the Survival of ALS Model Mice by
      Inhibiting the NF-kB Pathway.
AB  - Amyotrophic lateral sclerosis (ALS) is a chronic, fatal neurodegenerative
      disorder characterized by the progressive loss of upper and lower motor neurons.
      Currently, there is no effective drug for ALS. Recent studies in ALS model mice
      have shown that insulin-like growth factor-1 (IGF1) may be a promising
      therapeutic drug. We demonstrate that self-complementary adeno-associated virus
      serum type 9 encoding the human IGF1 (scAAV9-hIGF1) could significantly postpone
      the onset and slow down the progression of the disease owning to inhibiting the
      NF-kappaB signaling pathway. Furthermore, the results were supported by
      experiments in which the CRISPR/Cas9 system was used to knock-down IGF1 in ALS
      mice (mIGF1). Our data indicate that IGF1-mediated suppression of NF-kappaB
      activation in microglia is a novel molecular mechanism underlying MN death in
      ALS. It provides new insight into IGF1 and points toward novel therapeutic
      targets of IGF1 in ALS.

PMID- 29447859
TI  - Man With Bumps on His Shin.

PMID- 29447860
TI  - Man With Chest Pain and Lump in Neck.

PMID- 29447861
TI  - Improving the Quality of Emergency Care for Transgender Patients.

PMID- 29447862
TI  - Risk Stratifying Febrile Infants: A Moving Target.

PMID- 29447863
TI  - Best Save for Retirement.

PMID- 29447864
TI  - Choosing Sunshine.

PMID- 29447866
TI  - Clinical Decision Aids or Clinician Gestalt? Hard to Know Which Is Better:
      Answers to the September 2017 Journal Club Questions.

PMID- 29447867
TI  - Male With Sore Throat.

PMID- 29447868
TI  - Infant With a Diffuse Rash and a Fever.

PMID- 29447869
TI  - Hyperactive Child With Chest Pain.

PMID- 29447870
TI  - Ceiling Effect Is Not the Only Effect.

PMID- 29447871
TI  - In reply.

PMID- 29447872
TI  - Comparison of Intravenous Ketorolac at Three Single-Dose Regimens.

PMID- 29447873
TI  - In reply.

PMID- 29447874
TI  - In reply.

PMID- 29447875
TI  - A Commentary: Do alpha2-Adrenergic Agonists Decrease the Symptoms Associated With
      Opioid Withdrawal?

PMID- 29447876
TI  - Elderly Woman With Decreased Right-Sided Vision.

PMID- 29447877
TI  - Adolescent With a Non-Healing Thigh Injury.

PMID- 29447878
TI  - Risk of childhood otitis media with focus on potentially modifiable factors: A
      Danish follow-up cohort study.
AB  - INTRODUCTION: Otitis media is the primary cause of antibiotic prescription in
      children. Two-thirds of all children experience at least one episode of otitis
      media before the age of 7 years. The aim of this study was to characterise the
      attributable effect of several modifiable risk exposures on the risk of >3
      episodes of otitis media at age 18 months and 7 years within a large prospective
      national birth cohort. METHODS: The study used the Danish National Birth Cohort
      comprising information about otitis media and risk exposures from more than
      50,000 mother-child pairs from the period 1996-2002. Logistic regression models
      were used to estimate odds ratios for the risk factors and to calculate the
      population attributable fraction. RESULTS: Short time with breastfeeding, early
      introduction to daycare, cesarean section, and low compliance to the national
      vaccination program were all associated with an increased risk of >3 episodes of
      otitis media at 18 months of age and at 7 years of age. The fraction of children
      with otitis media attributed from breastfeeding lasting for less than 6 months
      was 10%. Introduction to daycare before the age of 12 months attributed with 20%
      of the cases of >3 episodes of otitis media. CONCLUSIONS: Short duration of
      breastfeeding, early introduction into daycare, cesarean section, and low
      compliance with the national vaccination program increased the risk of
      experiencing >3 episodes of otitis media at 18 months, and at 7 years of age.
      These are factors that all can be modulated.

PMID- 29447879
TI  - Parental preferences for the first consultation for microtia.
AB  - OBJECTIVES: The aim of our study was to investigate subjective information
      concerning parental experiences and preferences with regard to the initial
      information that is provided right after the birth of a child with microtia. The
      analysis of these data is intended to help professionals improve the way in which
      such conversations are conducted. As a result, future parents may feel better
      informed and, hence, better fit to cope with challenges they may encounter having
      a child with microtia. METHODS: A self-administered questionnaire was sent to 106
      parents and caretakers of children with microtia who visited the annual
      International Microtia and Atresia Conference in the Netherlands, May 2016.
      RESULTS: Eighty-seven questionnaires were returned (response rate 82%). Results
      revealed that 26% of the participants did not receive any information about the
      condition in the perinatal period. Participants who did receive information right
      after birth were informed by pediatricians and otolaryngolosits in most of the
      cases. Plastic surgeons and maxillofacial surgeons were the less commonly serving
      specialties in this role. A majority of the participants experienced their
      informing consultation as either being "terrible", or "bad". Parents desired more
      information about all domains regarding microtia. Development, clothing and
      appearance, and psychology were believed to be the least important domains.
      CONCLUSIONS: Parents are dissatisfied with several aspects of the initial
      information that is provided right after the birth of a child with microtia. We
      believe that there is a need for correct information and patient- and family
      centered care administered by multiple disciplines.

PMID- 29447880
TI  - Analysis of risk factors associated with unilateral hearing loss in children who
      initially passed newborn hearing screening.
AB  - OBJECTIVE: To analyze 2007 Joint Committee on Infant Hearing (JCIH) risk factors
      in children with confirmed unilateral hearing loss (UHL) who initially passed
      newborn hearing screening. METHODS: Retrospective record review of 16,108 infants
      who passed newborn hearing screening but had one or more JCIH risk factors
      prompting subsequent follow-up through the universal newborn hearing screening
      (UNHS) program in Virginia from 2010 to 2012. The study was reviewed and
      qualified as exempt by the Virginia Commonwealth University Institutional Review
      Board (IRB) and the Virginia Department of Health. RESULTS: Over the 2-year study
      period, 14896 (4.9% of total births) children passed UNHS but had the presence of
      one or more JCIH risk factor. Ultimately, we identified 121 babies from this
      group with confirmed hearing loss (0.7%), with 48 babies (0.2%) showing UHL. The
      most common risk factors associated with the development of confirmed UHL after
      passing the initial screen were neonatal indicators, craniofacial anomalies,
      family history, and stigmata of syndrome associated with hearing loss.
      CONCLUSION: Neonatal indicators and craniofacial anomalies were the categories
      most often found in children with confirmed unilateral hearing loss who initially
      passed their newborn hearing screen. While neonatal indicators were also the most
      common associated risk factor in all hearing loss, craniofacial abnormalities are
      relatively more common in children with UHL who initially passed newborn hearing
      screening. Further studies assessing the etiology underlying the hearing loss and
      risk factor associations are warranted.

PMID- 29447881
TI  - Tympanostomy tubes for serous otitis media and risk of recurrences.
AB  - OBJECTIVES: To determine the value of tympanostomy tubes (TTs) in the management
      of serous otitis media (SOM) and the risk factors for SOM recurrence. METHOD:
      This single-centre cohort study was performed in the University hospital of
      Amiens, France; and concerned 215 under-12 children having undergone at least one
      bilateral TT (Shepard grommet-type) placements for SOM. RESULTS: The mean TT
      retention time was 10 months. SOM recurred in 79 children (62.79%) and thus
      required a second TT placement (bilaterally in 90% of these cases). Overall,
      29.3% of the patients underwent a total of two TT placements, 5.58% underwent
      three placements and 0.93% underwent four placements. After their first-ever TT
      placement, 17 children had complications: 10 cases of otorrhoea (4.6%), 4 cases
      of retraction pocket (1.9%) and 3 perforations of the tympanic membrane (1.4%).
      At last follow-up, the most common complications were tympanosclerosis (6.9%) and
      perforation of the tympanic membrane (6.5%). In a multivariate analysis, the only
      significant risk factors for SOM recurrence were age below 48 months at the time
      of TT placement, and a TT retention time below 9 months. In contrast, a history
      of allergy, gastro-oesophageal reflux, prematurity or passive smoking were not
      significantly associated with recurrence. CONCLUSION: Age at the time of TT
      placement and the TT retention time were significantly associated with SOM
      recurrence. The TT retention time and the number of TT placements were not
      associated with the risk of long-term complications.

PMID- 29447882
TI  - Acute external otitis as debut of acute myeloid leukemia - A case and review of
      the literature.
AB  - Acute leukemia is a well known childhood cancer. The relation between leukemia
      and otological symptoms has long been established but is highly rare as a debut
      symptom of leukemia. External otitis is a common condition affecting many
      children, and most cases are successively treated with topical medicine. Here we
      present a child with acute external otitis later shown to be the debut symptom of
      acute myeloid leukemia, to our knowledge the first specific case described. We
      have reviewed the literature to find red flags for suspicion of severe disease in
      case of acute external otitis.

PMID- 29447883
TI  - Whole exome sequencing identifies a pathogenic mutation in WFS1 in two large
      Chinese families with autosomal dominant all-frequency hearing loss and prenatal
      counseling.
AB  - OBJECTIVES: To identify the pathogenic mutation and provide prenatal counseling
      and diagnosis in two large Chinese families with autosomal dominant all-frequency
      hearing loss. METHODS: Whole exome sequencing technology was used to identify the
      pathogenic mutation of the two families. In addition, 298 patients with sporadic
      hearing loss and 400 normal controls were studied to verify the
      mutation/polymorphism nature of the identified variant. Prenatal diagnosis was
      carried out. RESULTS: A rare missense mutation c.2389G > A (p.D572N) in the
      Wolframin syndrome 1 (WFS1) gene was identified. It was reported in only one
      previous Chinese study, and never in other populations/ethnicities. The mutation
      was also found in one patient with sporadic hearing loss (1/298, 0.3%). A healthy
      baby was born after prenatal diagnosis. CONCLUSION: Our findings strongly suggest
      that the c.2389G > A mutation in WFS1 is associated with all-frequency hearing
      loss, rather than low- or high-frequency loss. So far, the mutation is only
      reported in Chinese. Prenatal diagnosis and prenatal counseling is available for
      these two Chinese families.

PMID- 29447884
TI  - Knowledge and attitudes of early childhood development practitioners towards
      hearing health in poor communities.
AB  - OBJECTIVE: Within the educational sector of low-and middle-income countries
      (LMICs), formal and informal early childhood development (ECD) centers are often
      the first point of contact for majority of children. Since early hearing
      detection services are mostly absent in LMICs, these ECD centers may serve as the
      first point of access to screenings for these children. ECD practitioner
      awareness regarding hearing and hearing loss is essential for the successful
      implementation of hearing screening programs. This study thus investigated the
      current knowledge and attitudes of ECD practitioners towards childhood hearing
      loss in a community representative of typical LMIC contexts. METHOD: Purposive
      sampling was used to identify ECD centers and participants across a community.
      Thereafter, a cross-sectional quantitative survey (23 items) was adminstered
      amongst 82 ECD practitioners. RESULTS: More than 80% of ECD practitioners
      correctly identified genetics and ear infections as etiological factors of
      hearing loss. Gaps in knowledge regarding identification techniques for children
      3-6 years of age and the impact of hearing loss in the classroom were evident.
      ECD personnel's duration of experience had a significant effect on overall
      knowledge and attitude (p < .05; F (1,53) = 8.68). ECD personnel displayed a
      positive attitude towards children receiving a hearing test (88.3%) and almost
      all participants indicated the need for more information regarding hearing loss
      (93.5%). CONCLUSIONS: This study demonstrated a general readiness amongst ECD
      practitioners for the implementation of ECD hearing screening programs in LMICs,
      however additional information and guidelines are needed to improve practitioner
      knowledge and attitudes.

PMID- 29447885
TI  - Pediatric head and neck squamous cell carcinoma: Patient demographics, treatment
      trends and outcomes.
AB  - OBJECTIVES: To examine patient demographics, temporal and treatment trends, and
      survival outcomes of pediatric non-nasopharyngeal head and neck squamous cell
      carcinomas using the National Cancer Database. METHODS: The National Cancer
      Database was queried for pediatric patients (age 0-19 years) diagnosed with
      squamous cell carcinoma of the head and neck (including oral cavity, oropharynx,
      nasal cavity, larynx, hypopharynx, and salivary glands) from 2004 to 2013.
      RESULTS: Of 159 patients identified, the majority had oral cavity SCC (55%).
      There was no discernable change in incidence trends over the study period with
      the number of cases per year ranging from 10 to 20 (R2 = 0.174). The predominant
      treatment regimen for the nasal cavity was trimodality (surgery, radiation, and
      chemotherapy) treatment (29%), chemotherapy and radiation for the oropharynx
      (40%), and surgery alone for salivary gland (47%), oral cavity (44%), and larynx
      (22%). The 5-year overall survival for the entire cohort was 74% and by subsite:
      oral cavity (66%), oropharynx (68%), nasal cavity (75%), and larynx (95%).
      Laryngeal disease had statistically significant longer survival when compared to
      oral cavity (p = .031) or oropharynx (p = .029). CONCLUSION: Although pediatric
      non-nasopharyngeal head and neck squamous cell carcinomas are rare, practitioners
      should be aware of this entity and consider it in the differential diagnosis of
      pediatric malignancies.

PMID- 29447886
TI  - Recurrences of surgery for antrochoanal polyps in children: A systematic review.
AB  - OBJECTIVES: The main purpose was to evaluate the recurrence rate after surgery
      for antrochoanal polyps (ACPs) in children; secondly, we have analyzed the rate
      of recurrence for different types of surgery and the risk factors involved.
      METHODS: We performed a systematic review searching PubMed and MEDLINE databases
      including English-language published studies from June 1989 to October 2017
      regarding surgical treatment of ACPs in children. RESULTS: We included thirteen
      studies, eight were retrospective and five prospective, with 285 participants,
      the mean rate of recurrence after ACPs surgery was 15.0% (95% CI:11.0-20.0).
      Functional endoscopic sinus surgery (FESS) was the main type of surgery used for
      primary cases (75.4%) followed by the combined approach i.e. FESS with a
      transcanine sinusoscopy or mini Caldwell-Luc (14%), the Caldwell-Luc (CWL) (8%)
      and simple polypectomy (SP) (2.8%). Our analysis has demonstrated a significant
      reduction of recurrences using the combined approach 0% (95% CI: 0.0-8.0)
      compared with FESS 17.7% (95% CI: 12.8-23.4) or SP 50% (95% CI:15.7-84.3) (p <
      .05) but no significant differences with CWL 9.1% (95% CI: 1.1-29.2) and others
      surgical approaches (p > .05). The analysis of the possible risk factors involved
      in recurrences are inconclusive. CONCLUSION: Recurrences of ACPs in children are
      still high. The endoscopic sinus surgery is considered the first choice for
      primary treatment, whilst the external approach may be a valid option in case of
      recurrence. It seems that the combined approach could reduce recurrence rates in
      selected patients that cannot be completely managed with endoscopy.

PMID- 29447887
TI  - Thirty-day perioperative outcomes in resection of cervical lymphatic
      malformations.
AB  - INTRODUCTION: Limited information exists regarding short-term morbidity in the
      resection of lymphatic malformations. In order to make informed collaborative
      medical decisions, clinicians and families would benefit from information on 30
      day outcomes and the expected course associated with surgical excision of
      lymphatic malformations. METHODS: A retrospective chart review was conducted to
      develop a case series of patients who underwent resection of lymphatic
      malformation at a pediatric tertiary care center between June 1, 2007 and
      September 30, 2016. Demographic data, disease characteristics, operative details,
      post-operative care, and adverse events in the 30-day post-operative period were
      analyzed. Primary outcomes included facial nerve dysfunction, seroma formation,
      re-admission, and overall rate of any complications. Secondary outcomes included
      operative time, duration of stay, and duration of drain placement. RESULTS: Forty
      nine excisions were performed in 46 patients (21 male, 25 female). Median age was
      5 years. All but 7 cases were performed as the initial primary intervention.
      Median operative time was 96 min (range 22-224). Higher stage lesions (3-5) were
      associated with a longer operative time (p = .03). Median length of stay was 2
      days (range 0-35). Higher stage lesions were associated with an increased length
      of stay (p = .0004). Median duration of drain placement was 2 days (range 0-14),
      and was longer in higher stage lesions (p = .0002). Higher stage lesions (p =
      .002) and cases ultimately found to have residual disease (p = .019) were
      associated with an increased overall rate of complications; there was no
      association between cyst type and rate of complications. Seroma formation (31%)
      and transient facial nerve weakness (26%) were the two most common complications
      observed. There was no association between stage or cyst type and likelihood of
      seroma formation. Seromas resolved after a median duration of 3 months and
      transient facial nerve weakness resolved after a median duration of 2 months. 3
      patients required return to the OR and 1 patient was readmitted. CONCLUSION: The
      overall rate of adverse events after surgical excision of cervical lymphatic
      malformations is relatively low. Increased rates of complications can be expected
      with higher stage. Similarly, for these higher stage lesions, a longer operative
      time, hospital stay, and duration of drain placement can be expected.

PMID- 29447888
TI  - Pathogenesis of chronic rhinosinusitis in patients affected by beta-thalassemia
      major and sickle cell anaemia post allogenic bone marrow transplant.
AB  - OBJECTIVES: Sickle cell anemia (SCA) and beta -thalassemia major are well
      recognized beta-globin gene disorders of red blood cells associated to mortality
      and morbidity included bone morbidities due to ineffective erythropoiesis and
      bone marrow expansion, which affect every part of the skeleton. While there are
      an abundance of described disease manifestations of the head and neck, the manner
      of paranasal sinuses involvement and its relations to beta-thalassemia and SCA
      process was not studied yet. Therefore, the aim of this study was to investigate
      a possible increased risk of rhinosinusitis and the real pathogenetic mechanism
      of it, comparing these two hematological diseases using msCT, gold standard for
      paranasal sinuses evaluation. METHODS: A retrospective analysis of 90 patients
      affected by beta-thalassemia major or SCA (respectively 59 and 31) underwent
      allogeneic bone marrow transplantation (BMT), and 44 control subjects was
      performed. Both patient categories and control group have been subjected to
      hematological and radiological evaluation using 64-multidetector-row CT scanner
      without contrast injection. RESULTS: Statistical analysis reveals that patients
      of the two study groups exhibit a significantly increased risk of sinusitis in
      comparison with the normal controls (RR: 3.55 for beta-thalassemic pediatric
      subjects; RR: 3.35 for SCA pediatric subjects). A significant difference (p <
      0,5) was found between the beta -thalassemic patients on the one side, and SCA
      and control group on the other side, with regard to the evaluation of the typical
      anatomic alteration of maxillary sinus: beta-thalassemic children had significant
      increase in the bone thickness of anterior and lateral sinus walls and
      significant reduction in volume and density compared to SCA patients and control
      group, with normal conditions of these parameters. CONCLUSIONS: In these
      hematological patients, there is an increased incidence of sinonasal infections
      due their therapy-induced immunosuppression post transplantation. In beta
      thalassemic patients, furthermore, the specific anatomical variants play an
      important confounding factor in radiological interpretation of CT images.
      Therefore, a cranio-facial CT scan evaluation could be a useful tool in the
      management of upper airway infections after BMT and should be a routinely exams
      in order to avoid useless surgical or antibiotic approaches.

PMID- 29447889
TI  - Correlations between pediatric obstructive sleep apnea and longitudinal growth.
AB  - OBJECTIVES: Pediatric obstructive sleep apnea has a relatively high prevalence
      and has various negative health and behavioral consequences. Among the various
      complications of pediatric obstructive sleep apnea, growth disturbance is still
      controversial. METHOD: 745 pediatric subjects with obstructive sleep apnea
      diagnosed by in-lab polysomnography were enrolled, after excluding ineligible
      subjects with abnormal growth related factors. Height, weight, and BMI of
      enrolled patients were measured and statistically converted to z-scores, and the
      converted data were analyzed statistically with the polysomnographic results.
      Multiple linear regression were used to analyze the relationships between age,
      gender, z-score for weight, polysomnography results, and z-score for height.
      RESULTS: Patients with higher respiratory related index or lower mean/lowest
      oxygen saturation of PSG showed smaller z-score for height. Mean apnea hypopnea
      index and standard deviation of enrolled patients was 7.46 +/- 12.92, with
      moderate severity. And mean z-score for height and standard deviation was 0.21 +/
      1.15. Apnea hypopnea index, respiratory disturbance index, obstructive apnea
      index, and hypopnea index, respiratory related results of polysomnography, were
      statistically negative correlated with a z-score for height. And mean oxygen
      saturation and lowest oxygen saturation, oxygen saturation results of
      polysomnography, were statistically positive correlated with a z-score for
      height. CONCLUSIONS: Respiratory related results and oxygen saturation results of
      polysomnography show negative and positive correlation with z-score for height.
      Therefore, pediatric obstructive sleep apnea have a negative effect on
      longitudinal growth.

PMID- 29447890
TI  - Outcomes of adenoidectomy-alone in patients less than 3-years old.
AB  - OBJECTIVES: 1. Determine the percentage of patients under the age of 3 undergoing
      adenoidectomy-alone who require subsequent management of residual sleep
      disordered breathing (SDB).2. Characterize complications following adenoidectomy
      and determine if any perioperative factors are associated with intra-operative or
      post-operative complications and outcomes. METHODS: Case series with chart review
      was conducted including children seen at a tertiary care children's hospital
      between 2008 and 2012. Consecutive patients under the age of 3 who underwent
      adenoidectomy-alone were identified by billing codes. After excluding those with
      syndromes, partial adenoidectomies, and those without follow-up, 148 patients
      were included. Predictors of requiring additional surgery for SDB were evaluated
      using log-rank tests or Cox proportional hazards regression. RESULTS: Median age
      at time of initial adenoidectomy was 27.5 months (range 11-36 months) and the
      patient population was comprised of 66.2% males (n = 98/148) and 89.2% Caucasians
      (n = 132/148). 56.5% (n = 74/131) of patients continued to have residual symptoms
      of SDB and 34.5% (n = 51/148) underwent additional surgical intervention.
      Multivariable survival analysis revealed GERD (HR, 6.21; CI, 1.29-29.77, p =
      .022) and tonsil size (HR, 4.07; CI, 1.57-10.51, p = .004) were significant
      predictors of additional surgery in this group of patients under the age of 3.
      There was no observed difference in intra- and post-operative complication rates
      between patients with and without additional operative intervention. CONCLUSIONS:
      Residual SDB symptoms following adenoidectomy in patients less than 3 years of
      age are common and require additional surgery at a high rate. Medical
      comorbidities such as GERD and large tonsil size may help predict the need for
      additional surgery.

PMID- 29447891
TI  - Parents' experiences managing their child's complicated postoperative recovery.
AB  - OBJECTIVE: Tonsillectomy is commonly performed as same-day surgery and parents
      are heavily relied upon for management of children's postoperative recovery. The
      objective of this study was to provide an in-depth description of the experiences
      parents face when managing their child's complicated postoperative recoveries at
      home. METHODS: An exploratory qualitative study at an academic pediatric hospital
      in Eastern Canada was performed. Participants included 12 parents of children
      aged 3-6 years who underwent adeno/tonsillectomy and experienced unexpected
      outcomes or complications during the postoperative recovery period. Parents
      participated in semi-structured interviews within 6 months of their child's
      surgery. Interviews were transcribed verbatim and thematic analysis was used to
      identify themes in the parents' experiences. RESULTS: Parents described
      struggling to make the decision to come back to hospital, that adequate
      information does not prevent emotional difficulties, and feeling somewhat
      responsible for the unexpected outcome or complicated course of recovery.
      Communication with healthcare providers was considered very important in helping
      with the recovery process. CONCLUSION: This research helps to inform healthcare
      professionals about how they might better support families during complicated
      recovery processes. Areas of action may include clear communication, setting
      expectations, and psychosocial support.

PMID- 29447892
TI  - Differences in postoperative maladaptive behavioral changes between partial and
      total tonsillectomy patients.
AB  - INTRODUCTION: Behavioral difficulties associated with sleep-disordered breathing
      (SDB) improve after tonsillectomy, but surgery may lead to the development of
      short-term postoperative maladaptive behavioral changes (PMBCs). These PMBCs have
      not been compared between total and partial tonsillectomy patients. METHODS: SDB
      patients aged 1-6 years undergoing tonsillectomy were recruited. Parent phone
      surveys were conducted at 48-72 hours and 1-2 weeks postoperatively. Parents
      identified PMBCs using the Post-Hospital Behavior Questionnaire (PHBQ), scoring
      changes in behavior compared to baseline. PMBCs were defined by PHBQ scores >0
      and compared by one-tailed t-test. Postoperative pain was categorized as mild,
      moderate, and severe pain using the Parents' Postoperative Pain Measure (PPPM).
      Differences in pain levels were analyzed by Chi-squared test. A p-value <0.05 was
      deemed statistically significant. RESULTS: Seventy-eight children completed the
      study, with 29 total tonsillectomy and 49 partial tonsillectomy patients. At both
      time points after surgery, PHBQ scores were higher in total tonsillectomy
      patients than in partial tonsillectomy patients (3.41 +/- 3.53 versus 1.94 +/-
      2.25 at 2-3 days, p = .013). PMBCs were also more frequent in total than partial
      tonsillectomy patients (76% versus 59% at 2-3 days; 28% versus 7% at 1-2 weeks).
      Meanwhile, distribution of pain levels was similar between both partial and total
      tonsillectomy patients. CONCLUSIONS: Our study indicates that total tonsillectomy
      patients more frequently experience PMBCs than do partial tonsillectomy patients
      despite similar distributions in pain levels postoperatively. This difference in
      PHBQ scores between total and partial tonsillectomy patients should be further
      explored.

PMID- 29447893
TI  - iPhone otoscopes: Currently available, but reliable for tele-otoscopy in the
      hands of parents?
AB  - OBJECTIVES: Tele-otoscopy has been validated for tympanostomy surveillance and
      remote diagnosis when images are recorded by trained professionals. The CellScope
      iPhone Otoscope is a device that may be used for tele-otoscopy and it enables
      parents to record their children's ear examinations and send the films for remote
      physician diagnosis. This study aims to determine the ability to diagnose, and
      the reliability of the diagnosis when utilizing video exams obtained by a parent
      versus video exams obtained by an otolaryngologist. METHODS: Parents of children
      ages 17 years or younger attempted recordings of the tympanic membrane of their
      children with the CellScope after a video tutorial; a physician subsequently used
      the device to record the same ear. Recordings occurred prior to standard
      pediatric otolaryngology office evaluation. Later, a remote pediatric
      otolaryngologist attempted diagnosis solely based on the videos, blinded to
      whether the examination was filmed by a parent or physician. Interrater
      reliability between video diagnosis and original diagnosis on pneumatic otoscopy
      was measured, and objective tympanic membrane landmarks visualized on the films
      were recorded. RESULTS: Eighty ears were enrolled and recorded. There was low
      interrater agreement (k = 0.42) between diagnosis based on parent videos as
      compared with pneumatic otoscopy. There was high agreement (k = 0.71) between
      diagnosis based on physician videos and pneumatic otoscopy. Physician videos and
      parent videos had only slight agreement on objective landmarks identified (k =
      0.087). CONCLUSIONS: iPhone otoscopy provides reliable tele-otoscopy images in
      when used by trained professionals but, currently, images obtained by parents are
      not suitable for use in diagnosis.

PMID- 29447894
TI  - Cochlear implantation in pediatric patients with Cockayne Syndrome.
AB  - Cockayne Syndrome (CS) is a rare, autosomal recessive disorder characterized by a
      spectrum of phenotypic abnormalities, including progressive sensorineural hearing
      loss (SNHL) that involves both peripheral and central components. To date, a
      single series of CS patients undergoing cochlear implant (CI) placement has been
      reported; this study reports on additional previously unreported pediatric CI
      recipients. Subjective benefits were noted early after activation in both
      patients, and speech perception scores improved over time as well, varying from
      42 to 70% (versus 0-12% previously). Thus, we report that cochlear implantation
      in pediatric patients with CS can be effective in the management of progressive
      SNHL.

PMID- 29447895
TI  - Total congenital sternal cleft isolated in a newborn of 20 days: Rare case.
AB  - Sternal clefts are rare malformations, especially in their complete form, which
      results from a lack of fusion of the sternal bars, which is normally done at the
      9th week of intra uterine life. The incomplete form is often associated with
      other malformations of the chest wall, or falling within the framework of a
      polymalformative syndrome, the diagnosis is easy, being done with the inspection
      and the palpation, the paraclinical examinations are useful for confirming the
      diagnosis. We report the case of a total congenital sternal cleft isolated in an
      asymptomatic 20-day-old newborn. Thoracic CT, with threedimensional
      reconstructions, without injection of the contrast product confirmed the
      diagnosis, showing the presence of two hemistonids hypoplastic. The aim of our
      work is to draw attention to this pathology from birth because surgery must be
      undertaken during the first weeks of life to protect the heart and large vessels
      from any trauma, to improve respiratory dynamics and for aesthetic reasons.

PMID- 29447896
TI  - Bony cochlear nerve canal stenosis in pediatric unilateral sensorineural hearing
      loss.
AB  - OBJECTIVES: This study was performed to evaluate the frequency of bony cochlear
      nerve canal (BCNC) stenosis and its clinical significance in pediatric patients
      with unilateral sensorineural hearing loss (SNHL) of unknown etiology. MATERIALS
      AND METHODS: We analyzed the medical records and temporal bone computed
      tomography (CT) results of patients less than 13 years of age with a diagnosis of
      unilateral SNHL of unknown etiology between July 2007 and July 2017. We compared
      the BCNC diameter between both sides and analyzed the age at diagnosis, degree of
      hearing loss, and accompanying inner ear anomalies. RESULTS: In 42 patients, the
      mean age at diagnosis was 7.4 +/- 3.6 years, and the average hearing level in the
      affected ear was 87.9 +/- 20.0 dB HL (decibels hearing level). The average
      diameter of the BCNC was 1.22 +/- 0.75 mm on the affected side and 1.96 +/- 0.52
      mm on the normal side. The most suitable criterion for BCNC stenosis appeared to
      be a diameter of 1.2 mm by the recursive partitioning procedure. With application
      of this criterion, the rate of BCNC stenosis was significantly greater on the
      affected side than on the normal side (52.4% vs. 4.8%, respectively; P < 0.05). A
      narrow internal acoustic canal was found in two patients, and vestibular and
      cochlear anomalies were found in three patients each. CONCLUSIONS: Our results
      suggest that it is reasonable to set a diameter of 1.2 mm as a cutoff for BCNC
      stenosis, and also that BCNC stenosis is a common cause of unilateral SNHL of
      unknown etiology in childhood.

PMID- 29447897
TI  - Pattern of allergic rhinitis among children in Ekiti, Nigeria.
AB  - BACKGROUND: Allergic rhinitis is a chronic and recurrent nasal condition. It is
      often neglected in children with late presentation. This study aimed at
      determining the prevalence, sociodemographic features, comorbid illnesses,
      complications and quality of life in children with allergic rhinitis in the study
      institution. MATERIALS AND METHODS: This is a prospective hospital based study of
      children with allergic rhinitis in Ekiti state university teaching hospital, Ado
      Ekiti. The study was carried out in ENT department over a period of two years
      (between June 2015 to May 2017). Informed consent was obtained from the
      parents/guardian/patients and consented patients were enrolled into the study.
      Data were obtained by pretested interviewers assisted questionnaire. Details of
      their history, physical examination and investigations were carried out and
      findings were documented. All data obtained were descriptively analysed using
      SPSS version 18.0 and presented in simple tables and charts. Ethical clearance
      was sought for and obtained from the ethical committee of the hospital. RESULTS:
      A total of 4341 patients were seen out of which 265 were children with allergic
      rhinitis. Prevalence of allergic rhinitis in children in this study was 6.1%.
      There were 63.0% males with male to female ratio of 2:1. Allergic rhinitis was
      peaked at preschool age group (1-5 years) accounted for 47.9%. A total of 42.3%
      participants were living in urban setting while 57.7% were from rural setting.
      Majorities (40.4%) of the patients were in nursery and parent's major occupation
      was mainly farming in 27.2%. There was positive family history of allergy in
      54.7% patients. Perennial allergic rhinitis were noted in 63.8% patients while
      seasonal allergic rhinitis were noted in 36.2% patients. Major form of allergens
      was inhalant 81.8% and the least form of allergen was ingestant 5.7%. The
      commonest identified trigger factors among the study population were as follows:
      dust, cold weather and smoke which were accounted for 59.6%, 37.4% and 18.9% of
      the study patients respectively. Other noted triggering factors were soap and
      perfume which accounted for 4.2% and 1.1% respectively. Major associated comorbid
      illnesses among the patients were tonsils hypertrophy, adenoid hypertrophy and
      inferior turbinate hypertrophy which accounted for 55.5%, 46.4% and 40.4%
      respectively. Clinical presentations of allergic rhinitis in this study were
      mainly 75.8% nasal blockage, 65.3% runny nose and 8.5% recurrent sneezing.
      Commonest complications of allergic rhinitis were 35.1% pharyngitis, 32.1% otitis
      media and 28.3% headache. Treatment of allergic rhinitis leads to improvement on
      the clinical features in 90.1% patients. No significant improvement in clinical
      features were noticed in 9.8% patients. None of the studied patients reported
      worse clinical condition after treatment of allergic rhinitis. No mortality was
      recorded from allergic rhinitis in this study. CONCLUSION: Allergic rhinitis
      affect all paediatric age group and there were delayed presentation in the
      participants. There were associated comorbid illnesses, complications and
      affectation of quality of life at presentation in majority of the patients.

PMID- 29447898
TI  - Challenges and outcomes of cholesteatoma management in children with Down
      syndrome.
AB  - INTRODUCTION: The high incidence of chronic otitis media with effusion and
      Eustachian tube dysfunction in children with Down syndrome (DS) may predispose
      them to cholesteatoma formation. Establishing the diagnosis, choosing the
      appropriate operative intervention, and post-operative care can be challenging.
      OBJECTIVE: To describe management strategies for cholesteatoma diagnosis,
      surgical treatment, and post-operative management in children with Down syndrome.
      METHODS: Retrospective case series of 14 patients (17 total ears) with Down
      syndrome diagnosed with cholesteatoma over a 9-year period. RESULTS: A total of
      14 patients with cholesteatoma (3 with bilateral disease) were analyzed. Thirteen
      ears (76.5%) had >=2 tympanostomy tubes insertions prior to cholesteatoma
      diagnosis, and otorrhea and hearing loss were the most common presenting
      symptoms. Common pre-operative CT scan findings included mastoid sclerosis and
      ossicular erosion. The average age at first surgery was 9.8 years, and the
      average follow-up was 4.3 years. For acquired cholesteatoma, most ears were
      managed with canal wall up (CWU) approaches, but ultimately 6/15 (40.0%) required
      canal wall down (CWD) approaches. Postoperatively, 3 (20.0%) ears developed new
      tympanic membrane retraction pockets, but no recurrent cholesteatoma. Four
      (26.7%) ears developed recurrent disease, and 3 (20.0%) had residual disease at
      secondary procedures. Ossiculoplasty was performed in 4 ears. Twelve (70.6%) ears
      were rehabilitated with hearing aids or FM systems. CONCLUSIONS: The diagnosis of
      cholesteatoma in Down syndrome was associated with otorrhea, hearing loss, and CT
      scan findings of ossicular erosion and mastoid sclerosis. Most cases were managed
      with CWU surgical approaches. Hearing aid use was common post-operatively.

PMID- 29447899
TI  - Geographic health disparities in the Los Angeles pediatric esophageal foreign
      body population.
AB  - OBJECTIVE: To assess geographical sociodemographic differences in the pediatric
      esophageal foreign body population of Los Angeles. METHODS: We retrospectively
      reviewed the medical records of 128 consecutive pediatric patients at Children's
      Hospital Los Angeles (CHLA) from 2014 to 2017 with a diagnosis of a retained
      foreign body in the esophagus removed by rigid or flexible esophagoscopy.
      Sociodemographic information including zip code of residence was extracted and
      analyzed with Chi-square, Fisher's exact test, and multivariable logistic
      regression. RESULTS: The average age of patients with a retained esophageal
      foreign body in this study was 2.5 years old, 52.3% were male, 91.4% had no past
      medical history, 53.1% were Hispanic, 82.0% had public health insurance, and
      63.3% were transfers from an outside hospital. The most common foreign body
      removed was a coin. There were no significant differences in gender, race, type
      of health insurance, or income between patients that lived within 10 miles of
      CHLA versus farther than 10 miles. On multivariable analysis, zip codes with a
      high volume of esophageal foreign bodies were more likely to be lower income
      neighborhoods. Gender, race, type of health insurance, and distance from CHLA
      were not risk factors for zip codes with a high volume of esophageal foreign
      bodies. CONCLUSION: Geographic areas in the greater Los Angeles community with a
      high volume of retained esophageal foreign bodies requiring endoscopic removal at
      our institution are associated with lower income neighborhoods. Further studies
      should be performed to better understand health disparities within the U.S.
      pediatric esophageal foreign body population.

PMID- 29447900
TI  - Microbiology and antibiotic therapy of subperiosteal orbital abscess in children
      with acute ethmoiditis.
AB  - OBJECTIVE: The objective of this study was to investigate the microbiological
      cultures and the management of acute ethmoiditis complicated by subperiosteal
      orbital abscess (SPOA) in a pediatric population. METHODS: The medical records of
      children under 18 years old was performed in a tertiary referral pediatric center
      from January 2009 to April 2017. Clinical examination, computed tomography scans,
      medical and surgical treatments were reviewed and compared to other studies in
      literature. RESULTS: One hundred and twenty-nine children were hospitalized for
      acute ethmoiditis. Among them, forty eight were complicated by SPOA. The mean age
      of these children were 7 years (range 10 months-16 years). Thirtyfour underwent
      surgical drainage; for the others the medical treatment was sufficient.
      Microbiological samples were obtained during the surgical intervention and were
      contributive in 91% of cases. Streptococcus spp was the most frequently
      encountered bacteria (60% of cases). We also found anaerobic bacteria (12%), and
      Staphylococcus aureus (12%). 94% of children received two intravenous antibiotics
      (a third-generation cephalosporin and metronidazole) for a mean duration of four
      days. Then the oral treatment was based on amoxicillin-clavulanate during about
      8.5 days. All children were cured without sequelae. CONCLUSIONS: For five years
      Streptococcus milleri, Staphylococcus spp and anaerobic bacteria are on the rise
      in acute ethmoiditis complicated by SPOA. That is why antibiotics must be adapted
      to these bacteria even in children under ten years old.

PMID- 29447901
TI  - Hospital cost analysis of children with preseptal cellulitis.
AB  - OBJECTIVE: Hospitalization of the children with preseptal cellulitis creates a
      burden on healthcare costs. This study aimed to analyze the hospital costs for
      preseptal cellulitis and determine the factors contributing. METHODS: Children,
      between 1 and 18 years old, who were admitted to hospital for preseptal
      cellulitis from May 2013 to December 2016 were included in the study. Patients
      were divided into groups by age (under or equal to five years and older than five
      years) and by the presence of sinusitis. Demographics, length of stay and total
      and categorical hospital costs were evaluated retrospectively. RESULTS: The study
      included 54 patients with a mean age of 5 years. Thirty one of the patients were
      under five years of age. The most common symptoms were swelling (94.4%) and
      redness (83.3%) around eye. Among the predisposing factors, sinusitis was the
      most common one (37%). The average length of stay was 4.5 days. Total hospital
      cost of all patients was $11,841. Antibiotic costs (37%) and inpatient floor
      costs (36%) were the greatest expenditures. Between age groups, length of stay
      was longer, and inpatient floor and antibiotic costs were significantly higher in
      the group of >5 years (p = 0.007, p = 0.004 and p = 0.001, respectively). In the
      group with sinusitis, length of stay was longer, and all hospital costs were
      significantly higher compared to the group without sinusitis (p < 0.001). There
      was a strong, positive correlation between length of stay and hospital costs (r =
      0.854, n = 53, p < 0.001). Sinusitis was a significant factor (p < 0.001) for
      longer length of stay, but age was not (p = 0.841). CONCLUSION: Sinusitis was
      found to be an important factor contributing to longer length of stay and higher
      hospital costs for preseptal cellulitis. Oral or ambulatory intravenous
      antimicrobial treatment strategies might decrease the hospital expenditure in
      these patients; however care should be taken in the presence of sinusitis.

PMID- 29447902
TI  - The erythrocyte osmotic resistance test as screening tool for cholesterol-related
      lysosomal storage diseases.
AB  - BACKGROUND: Erythrocyte volume regulation and membrane elasticity are essential
      for adaptation to osmotic and mechanical stress, and life span. Here, we
      evaluated whether defective cholesterol trafficking caused by the rare lysosomal
      storages diseases (LSDs), Niemann-Pick type C (NPC) and Lysosomal acid lipase
      (LAL) deficiency (LALD) impairs these properties. Moreover, we tested whether
      measurements of cholesterol membrane content and osmotic resistance serve as a
      screening test for these LSDs. METHODS: Patients were genotyped for mutations in
      NPC1, NPC2, or LIPA genes. We measured LSD plasma biomarkers and LAL activity.
      Red blood cells (RBC) membrane cholesterol content was evaluated in 73 subjects.
      Osmotic resistance tests (ORT) were conducted in 121 blood samples from LSD
      suspected patients and controls. RESULTS: We did not find statistically
      significant differences between RBC cholesterol content between subjects and
      controls. However, the ORT, particularly at 0.49% (w/v) hypotonic sodium chloride
      solution, revealed a significant higher osmotic resistance in LSDs patients than
      in controls. We established a cut-off value of <=51% of haemolysis with
      sensibility and specificity values of 80% and 70%, respectively. CONCLUSIONS: NPC
      and LALD do not alter cholesterol content in the RBC membrane but increase
      osmotic resistance. Therefore, ORT serves as screening test for the studied LSDs.

PMID- 29447903
TI  - Mass spectrometric identification of bromotryptophan containing conotoxin
      sequences from the venom of C. amadis.
AB  - Four 30 residue conotoxin have been identified from the venom of C. amadis. MS/MS
      analysis of crude venom subjected to global reduction/alkylation yielded
      fragmentation patterns, which permitted searching and matching with a database of
      putative mature toxin sequences obtained from transcriptomic analysis. Of the
      four sequences identified, Am3408(Am6.1b), Am3452(Am6.1c), Am3136(Am6.2a) and
      Am3214(Am6.2b), three contain bromotryptophan residues, while an additional post
      translational modification, gamma carboxylation of glutamic acid, is present in
      Am3408(Am6.1b)/3452(Am6.1c). The conotoxins belong to the O1/O2 gene superfamily
      and possess cysteine framework VI/VII. While, the cysteine patterns show a
      similarity to omega conotoxins, the three C. amadis peptides are highly
      negatively charged and possess a significant content of hydrophobic residues.

PMID- 29447904
TI  - Intraspecific venom variation in southern African scorpion species of the genera
      Parabuthus, Uroplectes and Opistophthalmus (Scorpiones: Buthidae, Scorpionidae).
AB  - Scorpion venoms comprise cocktails of proteins, peptides, and other molecules
      used for immobilizing prey and deterring predators. The composition and efficacy
      of scorpion venoms appears to be taxon-specific due to a coevolutionary arms race
      with prey and predators that adapt at the molecular level. The taxon-specific
      components of scorpion venoms can be used as barcodes for species identification
      if the amount of intraspecific variation is low and the analytical method is
      fast, inexpensive and reliable. The present study assessed the extent of
      intraspecific variation in newly regenerated venom collected in the field from
      geographically separated populations of four southern African scorpion species:
      three buthids, Parabuthus granulatus (Ehrenberg, 1831), Uroplectes
      otjimbinguensis (Karsch, 1879), and Uroplectes planimanus (Karsch, 1879), and one
      scorpionid, Opistophthalmus carinatus (Peters, 1861). Although ion signal
      patterns were generally similar among venom samples of conspecific individuals
      from different populations, MALDI-TOF mass spectra in the mass range m/z 700
      10,000 revealed only a few ion signals that were identical suggesting that
      species identification based on simple venom mass fingerprints (MFPs) will be
      more reliable if databases contain data from multiple populations. In general,
      hierarchical cluster analysis (HCA) of the ion signals in mass spectra was more
      reliable for species identification than counts of mass-identical substances in
      MFPs. The statistical approach revealed conclusive information about
      intraspecific diversity. In combination with a comprehensive database of MALDI
      TOF mass spectra in reflectron mode, HCA may offer a method for rapid species
      identification based on venom MFPs.

PMID- 29447905
TI  - Clinical relevance commentary in response to: The validity and clinical utility
      of the Disabilities of the Arm Shoulder and Hand questionnaire for hand injuries
      in developing country contexts: A systematic review.

PMID- 29447906
TI  - Cell death in neural precursor cells and neurons before neurite formation
      prevents the emergence of abnormal neural structures in the Drosophila optic
      lobe.
AB  - Programmed cell death is a conserved strategy for neural development both in
      vertebrates and invertebrates and is recognized at various developmental stages
      in the brain from neurogenesis to adulthood. To understand the development of the
      central nervous system, it is essential to reveal not only molecular mechanisms
      but also the role of neural cell death (Pinto-Teixeira et al., 2016). To
      understand the role of cell death in neural development, we investigated the
      effect of inhibition of cell death on optic lobe development. Our data
      demonstrate that, in the optic lobe of Drosophila, cell death occurs in neural
      precursor cells and neurons before neurite formation and functions to prevent
      various developmental abnormalities. When neuronal cell death was inhibited by an
      effector caspase inhibitor, p35, multiple abnormal neuropil structures arose
      during optic lobe development-e.g., enlarged or fused neuropils, misrouted
      neurons and abnormal neurite lumps. Inhibition of cell death also induced
      morphogenetic defects in the lamina and medulla development-e.g., failures in the
      separation of the lamina and medulla cortices and the medulla rotation. These
      defects were reproduced in the mutant of an initiator caspase, dronc. If cell
      death was a mechanism for removing the abnormal neuropil structures, we would
      also expect to observe them in mutants defective for corpse clearance. However,
      they were not observed in these mutants. When dead cell-membranes were visualized
      with Apoliner, they were observed only in cortices and not in neuropils. These
      results suggest that the cell death occurs before mature neurite formation.
      Moreover, we found that inhibition of cell death induced ectopic neuroepithelial
      cells, neuroblasts and ganglion mother cells in late pupal stages, at sites where
      the outer and inner proliferation centers were located at earlier developmental
      stages. Caspase-3 activation was observed in the neuroepithelial cells and
      neuroblasts in the proliferation centers. These results indicate that cell death
      is required for elimination of the precursor cells composing the proliferation
      centers. This study substantiates an essential role of early neural cell death
      for ensuring normal development of the central nervous system.

PMID- 29447907
TI  - Wilhelm His' lasting insights into hindbrain and cranial ganglia development and
      evolution.
AB  - Wilhelm His (1831-1904) provided lasting insights into the development of the
      central and peripheral nervous system using innovative technologies such as the
      microtome, which he invented. 150 years after his resurrection of the classical
      germ layer theory of Wolff, von Baer and Remak, his description of the
      developmental origin of cranial and spinal ganglia from a distinct cell
      population, now known as the neural crest, has stood the test of time and more
      recently sparked tremendous advances regarding the molecular development of these
      important cells. In addition to his 1868 treatise on 'Zwischenstrang' (now neural
      crest), his work on the development of the human hindbrain published in 1890
      provided novel ideas that more than 100 years later form the basis for
      penetrating molecular investigations of the regionalization of the hindbrain
      neural tube and of the migration and differentiation of its constituent neuron
      populations. In the first part of this review we briefly summarize the major
      discoveries of Wilhelm His and his impact on the field of embryology. In the
      second part we relate His' observations to current knowledge about the molecular
      underpinnings of hindbrain development and evolution. We conclude with the
      proposition, present already in rudimentary form in the writings of His, that a
      primordial spinal cord-like organization has been molecularly supplemented to
      generate hindbrain 'neomorphs' such as the cerebellum and the auditory and
      vestibular nuclei and their associated afferents and sensory organs.

PMID- 29447908
TI  - Primary lymphedema and other lymphatic anomalies are associated with 22q11.2
      deletion syndrome.
AB  - BACKGROUND: Lymphedema is an abnormal accumulation of interstitial fluid within
      the tissues. Primary lymphedema is caused by aberrant lymphangiogenesis and it
      has been historically classified based on age at presentation. Although most
      cases are sporadic, primary lymphedema may be familial or present in association
      with chromosomal abnormalities and syndromic disorders. To the best of our
      knowledge, primary lymphedema has never been described in patients with 22q11.2
      deletion syndrome. METHODS AND RESULTS: We identified 4 patients with 22q11.2
      deletion syndrome and primary lymphedema via our International 22q11.2 Deletion
      Syndrome Consortium. All patients underwent comprehensive clinical, laboratory
      and imaging assessments to rule out other causes of lymphedema. All patients had
      de novo typical deletions and family histories were negative for lymphedema.
      CONCLUSIONS: We report the novel association of primary lymphedema with 22q11.2
      deletion syndrome. Importantly, animal models demonstrated Tbx1 playing a
      critical role in lymphangiogenesis by reducing Vegfr3 expression in lymphatic
      endothelial cells. Moreover, the VEGFR3 pathway is essential for
      lymphangiogenesis with mutations identified in hereditary primary lymphedema.
      Accordingly, our findings provide a new insight into understanding cellular
      mechanisms of lymphangiogenesis disorders.

PMID- 29447910
TI  - Preventing non-contact ACL injuries in female athletes: What can we learn from
      dancers?
AB  - OBJECTIVES: To investigate the effects of dance experience and movement
      instruction on lower extremity kinematics and muscle activation during a landing
      task. DESIGN: Cross-sectional case control. SETTING: Laboratory setting.
      PARTICIPANTS: 27 female subjects (age 18-25) in 2 groups: dancers (n = 12) and
      non-dancers (n = 15). MAIN OUTCOME MEASURES: Lower extremity biomechanics during
      drop landing were analyzed. Subjects performed drop landings after watching an
      instructional video without verbal instructions (NI), followed by repeat
      assessment after watching the same videos with specific verbal instructions (VI).
      Surface electromyography (EMG) was used to measure the activation of gluteus
      maximus and medius during the deceleration phase of landings. Peak knee and hip
      frontal plane angles during landing were acquired using a 3-D motion capture
      system. RESULTS: Compared to non-dancers, dancers demonstrated generally greater
      gluteus maximus activation and a decreased knee abduction (i.e. valgus) angle
      during drop landing. A significant interaction showed that instruction led to
      increased knee valgus angle in non-dancers but not dancers (p = .014).
      CONCLUSIONS: Our findings suggest that experienced dancers demonstrate safer
      landing strategies compared to recreational athletes. Providing acute movement
      instruction was shown to disrupt the landing mechanics in those with no dance
      training experience.

PMID- 29447909
TI  - Phosphatidylserine-stimulated production of N-acyl-phosphatidylethanolamines by
      Ca2+-dependent N-acyltransferase.
AB  - N-acyl-phosphatidylethanolamine (NAPE) is known to be a precursor for various
      bioactive N-acylethanolamines including the endocannabinoid anandamide. NAPE is
      produced in mammals through the transfer of an acyl chain from certain
      glycerophospholipids to phosphatidylethanolamine (PE) by Ca2+-dependent or 
      independent N-acyltransferases. The epsilon isoform of mouse cytosolic
      phospholipase A2 (cPLA2epsilon) was recently identified as a Ca2+-dependent N
      acyltransferase (Ca-NAT). In the present study, we first showed that two isoforms
      of human cPLA2epsilon function as Ca-NAT. We next purified both mouse recombinant
      cPLA2epsilon and its two human orthologues to examine their catalytic properties.
      The enzyme absolutely required Ca2+ for its activity and the activity was
      enhanced by phosphatidylserine (PS). PS enhanced the activity 25-fold in the
      presence of 1 mM CaCl2 and lowered the EC50 value of Ca2+ >8-fold. Using a PS
      probe, we showed that cPLA2epsilon largely co-localizes with PS in plasma
      membrane and organelles involved in the endocytic pathway, further supporting the
      interaction of cPLA2epsilon with PS in living cells. Finally, we found that the
      Ca2+-ionophore ionomycin increased [14C]NAPE levels >10-fold in [14C]ethanolamine
      labeled cPLA2epsilon-expressing cells while phospholipase A/acyltransferase-1,
      acting as a Ca2+-independent N-acyltransferase, was insensitive to ionomycin for
      full activity. In conclusion, PS potently stimulated the Ca2+-dependent activity
      and human cPLA2epsilon isoforms also functioned as Ca-NAT.

PMID- 29447911
TI  - Fluorescent protein tagged hepatitis B virus capsid protein with long glycine
      serine linker that supports nucleocapsid formation.
AB  - Fusion core proteins of Hepatitis B virus can be used to study core protein
      functions or capsid trafficking. A problem in constructing fusion core proteins
      is functional impairment of the individual domains in these fusion proteins,
      might due to structural interference. We reported a method to construct fusion
      proteins of Hepatitis B virus core protein (HBc) in which the functions of fused
      domains were partially kept. This method follows two principles: (1) fuse
      heterogeneous proteins at the N terminus of HBc; (2) use long Glycine-serine
      linkers between the two domains. Using EGFP and RFP as examples, we showed that
      long flexible G4S linkers can effectively separate the two domains in function.
      Among these fusion proteins constructed, GFP-G4S186-HBc and RFP-G4S47-HBc showed
      the best efficiency in rescuing the replication of an HBV replicon deficient in
      the core protein expression, though both of the two fusion proteins failed to
      support the formation of the relaxed circular DNA. These fluorescent protein
      tagged HBcs might help study related to HBc or capsids tracking in cells.

PMID- 29447912
TI  - Immunogold-agglutination assay for direct detection of HPV-16 E6 and L1 proteins
      from clinical specimens.
AB  - HPV-16 infection is the most common cause of cervical cancer. As HPV-16
      transforms the cell, E6 oncoprotein is over-expressed. Therefore, molecular
      detection of HPV-16 E6 mRNA is now being used for diagnosis and prediction of
      cancer development. Besides detecting E6 mRNA, a rapid lateral flow detecting the
      E6 protein using enzyme immunoassay is also now on market with a sensitivity of
      53.5% for cervical intraepithelial neoplasia (CIN)-3 or more severe (CIN-3+).
      Here, an immunogold-agglutination assay was developed to detect not only HPV-16
      E6 protein but also L1, a major capsid protein found in the productive stage of
      the virus. Evaluation of this test using HPV-16 DNA positive cervical samples
      showed that the HPV-16 E6 immunogold-agglutination assay results correlated well
      with the progression of the cervical lesions, i.e., 10.34% of CIN-1, 68.75% of
      CIN-3 and 80% of cancer (CaCx) and none for healthy normal samples.
      Interestingly, the HPV-16 L1 protein was found in most of the cases with cancer
      indicating the possibility of virion production. Immunogold-agglutination assay
      for E6 protein is simpler, easier to be performed with a sensitivity of 73.1% for
      CIN-3+ suggesting a good method for laboratory diagnostic use.

PMID- 29447913
TI  - Microbiological surveillance of plasmid mediated colistin resistance in human
      Enterobacteriaceae isolates in Romagna (Northern Italy): August 2016-July 2017.
AB  - OBJECTIVES: To start a surveillance program to investigate the possible diffusion
      of mobilized colistin resistance genes in Enterobacteriaceae strains isolated in
      the Unit of Microbiology of the Great Romagna Hub Laboratory. METHODS: All the
      colistin resistant Enterobacteriaceae, isolated from August 1st 2016 to July 31st
      2017, were prospectively evaluated for mcr-1 and mcr-2. Backdated survey of mcr
      3, mcr-4 and mcr-5 was performed on the same group of isolates. Species
      identification was achieved by Vitek MS and the antibiotic susceptibility testing
      was performed both with Vitek-2 and Sensititre systems. Colistin resistant
      isolates were screened by PCR for the presence of the plasmid-mediated colistin
      resistance genes and amplicons were verified by sequencing. All mcr-1 positive
      isolates were subjected to MLST analysis. RESULTS: Over the total of 19053
      isolates belonging to Enterobacteriaceae, 90 were colistin resistant. The
      presence of mcr-1 was detected in 26 Escherichia coli. The overall prevalence of
      mcr-1 was 0.14%. The mcr-1 positive E. coli strains were assigned to 13 distinct
      sequence types (STs) according to MLST. CONCLUSIONS: The prospective
      epidemiological survey carried out in our study gave a glimpse of the plasmid
      mediated colistin resistance dissemination in Romagna. Since the prevalence rate
      of carbapenem resistant Enterobacteriaceae (CRE) in some hospital wards in our
      area is alarming, we underline the importance of a Surveillance Program to
      monitor the spread of the plasmid-mediated colistin resistance genes into MDR
      Gram-negative bacteria.

PMID- 29447915
TI  - Comparing Treatment of Acute Retinal Necrosis With Either Oral Valacyclovir or
      Intravenous Acyclovir.
AB  - PURPOSE: To compare the visual outcomes of patients with acute retinal necrosis
      (ARN) treated initially with intravenous acyclovir vs oral valacyclovir therapy.
      DESIGN: Retrospective, comparative, interventional case series. METHODS: Sixty
      two patients (68 eyes) with ARN, treated at Moorfields Eye Hospital (United
      Kingdom) between 1992 and 2016, were identified through the hospital's electronic
      database. Exclusion criteria included insufficient patient records or follow-up
      (<150 days). Fifty-six patients had unilateral ARN, while 6 had bilateral ARN.
      Patients who received intravenous acyclovir on diagnosis (n = 33) were compared
      with patients treated with oral valacyclovir (n = 29) across outcomes including
      best-corrected visual acuity, retinal detachment, severe vision loss, and other
      complications. The impact of adjunctive intravitreal antiviral and prophylactic
      barrier laser treatment was also assessed. RESULTS: Change in best-corrected
      visual acuity was not significantly different for eyes treated initially with
      intravenous therapy vs oral therapy over 5 years of follow-up data (P = .16).
      There was no difference in the rates of severe vision loss between the 2 groups
      (46% and 59%, respectively, P = .18), or of those eyes retaining good vision (28%
      vs 31%, respectively, P = .80). Retinal detachment occurred in 63% of cases and
      did not differ across treatment groups (62% vs 66%, respectively, P = .67).
      Barrier laser and intravitreal therapy had no effect on retinal detachment rate
      in either group. CONCLUSION: Oral valacyclovir is clinically equivalent to
      intravenous therapy in the management of ARN. Oral valacyclovir as an outpatient
      therapy-with or without intravitreal foscarnet-can therefore be considered as an
      acceptable alternative to inpatient therapy required for intravenous treatment.

PMID- 29447914
TI  - Progression of Primary Open-Angle Glaucoma in Diabetic and Nondiabetic Patients.
AB  - PURPOSE: To compare the rates of visual field (VF) loss and retinal nerve fiber
      layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients with or
      without type 2 diabetes mellitus (DM). DESIGN: Cohort study. METHODS: A total of
      197 eyes (55 eyes of 32 POAG patients with DM in POAG/DM group and 142 eyes of
      111 age-matched POAG patients without DM in POAG/DM- group) were included from
      the Diagnostic Innovations in Glaucoma Study (DIGS). Type 2 DM participants were
      defined by self-report of DM history and use of antidiabetic medication. The
      rates of VF loss and RNFL loss were compared in POAG eyes with and without DM
      using univariate and multivariable mixed-effects models. RESULTS: The median
      (interquartile range) follow-up was 5.7 years (4.0, 6.4). The mean rate of global
      RNFL loss in the POAG/DM group was 2-fold slower than in the POAG/DM- group
      overall (-0.40 MUm/year vs -0.83 MUm/year, respectively P = .01). Although a
      slower rate of VF mean deviation and pattern standard deviation loss was found in
      the POAG/DM group compared to the POAG/DM- group, the difference was not
      statistically significant. CONCLUSIONS: POAG patients with treated type 2 DM, who
      had no detectable diabetic retinopathy, had significantly slower rates of RNFL
      thinning compared to those without diagnosed DM.

PMID- 29447916
TI  - Helix formation and stability in membranes.
AB  - In this article we review current understanding of basic principles for the
      folding of membrane proteins, focusing on the more abundant alpha-helical class.
      Membrane proteins, vital to many biological functions and implicated in numerous
      diseases, fold into their active conformations in the complex environment of the
      cell bilayer membrane. While many membrane proteins rely on the translocon and
      chaperone proteins to fold correctly, others can achieve their functional form in
      the absence of any translation apparatus or other aides. Nevertheless, the
      spontaneous folding process is not well understood at the molecular level. Recent
      findings suggest that helix fraying and loop formation may be important for
      overall structure, dynamics and regulation of function. Several types of membrane
      helices with ionizable amino acids change their topology with pH. Additionally we
      note that some peptides, including many that are rich in arginine, and a
      particular analogue of gramicidin, are able passively to translocate across cell
      membranes. The findings indicate that a final protein structure in a lipid
      bilayer membrane is sequence-based, with lipids contributing to stability and
      regulation. While much progress has been made toward understanding the folding
      process for alpha-helical membrane proteins, it remains a work in progress. This
      article is part of a Special Issue entitled: Emergence of Complex Behavior in
      Biomembranes edited by Marjorie Longo.

PMID- 29447918
TI  - Chemical genetics in tumor lipogenesis.
AB  - Since cancer cells depend on de novo lipogenesis for energy supply, highly active
      membrane biosynthesis and signaling, enhanced fatty acid synthesis is a crucial
      characteristic of cancer cells. Hence, targeting lipogenic enzymes and signaling
      cascades is a very promising approach in developing innovative therapeutic agents
      for the fight against cancer. This review summarizes main aspects of altered
      fatty acid synthesis in cancer cells and emphasizes the power of chemical genetic
      approaches in identifying and analyzing novel anti-cancer drug candidates
      interfering with lipid metabolism.

PMID- 29447917
TI  - Insertion of Dengue E into lipid bilayers studied by neutron reflectivity and
      molecular dynamics simulations.
AB  - The envelope (E) protein of Dengue virus rearranges to a trimeric hairpin to
      mediate fusion of the viral and target membranes, which is essential for
      infectivity. Insertion of E into the target membrane serves to anchor E and
      possibly also to disrupt local order within the membrane. Both aspects are likely
      to be affected by the depth of insertion, orientation of the trimer with respect
      to the membrane normal, and the interactions that form between trimer and
      membrane. In the present work, we resolved the depth of insertion, the tilt
      angle, and the fundamental interactions for the soluble portion of Dengue E
      trimers (sE) associated with planar lipid bilayer membranes of various
      combinations of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1
      palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol (POPG), 1-palmitoyl-2-oleoyl
      sn-glycero-3-phosphoethanolamine (POPE), and cholesterol (CHOL) by neutron
      reflectivity (NR) and by molecular dynamics (MD) simulations. The results show
      that the tip of E containing the fusion loop (FL) is located at the interface of
      the headgroups and acyl chains of the outer leaflet of the lipid bilayers, in
      good agreement with prior predictions. The results also indicate that E tilts
      with respect to the membrane normal upon insertion, promoted by either the
      anionic lipid POPG or CHOL. The simulations show that tilting of the protein
      correlates with hydrogen bond formation between lysines and arginines located on
      the sides of the trimer close to the tip (K246, K247, and R73) and nearby lipid
      headgroups. These hydrogen bonds provide a major contribution to the membrane
      anchoring and may help to destabilize the target membrane.

PMID- 29447919
TI  - Expression of programmed cell death protein 1 (PD-1) and indoleamine 2,3
      dioxygenase (IDO) in the tumor microenvironment and in tumor-draining lymph nodes
      of breast cancer.
AB  - Programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO) are
      both immunosuppressive proteins. Here, we investigated the relationship between
      PD-1 and IDO in the tumor microenvironment (TME) and in tumor-draining lymph
      nodes (TDLNs) in breast cancer patients. First, the protein and mRNA expression
      levels of PD-1 and IDO in 20 frozen tissues were examined using Western blotting
      and real-time polymerase chain reaction. Second, 151 paraffin-embedded breast
      samples and 52 lymph node samples were analyzed by immunohistochemistry. Third,
      correlation and survival data for PD-1 and IDO in 963 breast tumor patients were
      mined using the cBio Cancer Genomics Portal. We found that the protein expression
      level of IDO was significantly increased in frozen tumor tissues (P = .005). From
      paraffin-embedded samples in the TME, PD-1+ cells were only located in the
      stroma, while IDO was expressed in myoepithelial, stromal, and tumor cells. PD-1
      and stromal IDO in the TME showed increased expression in tumors (P< .001 and P <
      .001, respectively). In TDLNs, PD-1+ cells were primarily located in the germinal
      centers (GCs), and IDO+ cells were primarily located in the paracortex. Normal
      lymph nodes expressed PD-1 and IDO at the same level as non-metastatic and
      metastatic lymph nodes (P = .151 and P = .812, respectively). According to
      cBioPortal, the correlation analysis showed that IDO and PD-1 had high
      correlation coefficients (r = 0.83). These findings suggest that there is a
      positive correlation between the expression of PD-1 and IDO and that blocking
      both PD-1 and IDO pathways may represent an attractive therapeutic strategy in
      breast cancer treatment.

PMID- 29447920
TI  - Overexpression of BCAT1 is a prognostic marker in gastric cancer.
AB  - As one form of branched-chain amino-acid transaminase (BCAT) enzymes, It has been
      found that up-regulation of BCAT1 is associated with poor prognosis in numerous
      types of tumors, but studies on the role of BCAT1 expression in gastric cancer
      (GC) are rare. The aims of this study were to detect BCAT1 expression in GC and
      to analyze its association with prognosis of GC patients. Microarray experiments
      were performed on the Affymetrix U133 plus 2.0 GeneChip Array. The protein and
      messenger RNA levels of BCAT1 were validated by immunohistochemistry and real
      time quantitative polymerase chain reaction in GC tissues and adjacent
      noncancerous tissues. Our study shows that the expression of BCAT1 significantly
      increased in human GC. Furthermore, it can also be found that BCAT1
      overexpression was associated with TNM stage (P < .05), local invasion (P < .05),
      Lauren type (P < .05), tumor classification (P < .05), lymph node metastasis (P <
      .05), and presence of distant metastasis (P < .05). Kaplan-Meier survival
      analysis revealed that high BCAT1 expression predicted significantly worse
      overall survival (P < .05), whereas multivariate Cox regression analysis showed
      that BCAT1 affects GC independently. In conclusion, up-regulation of BCAT1
      indicated a poor survival rate of GC and may serve as a useful marker for
      predicting the outcome of patients with GC.

PMID- 29447921
TI  - DNA demethylation of claudin-4 suppresses migration and invasion in laryngeal
      squamous carcinoma cells.
AB  - Claudin-4 (CLDN4) is a member of the claudin transmembrane protein family, which
      consists of integral membrane proteins that are components of the epithelial cell
      tight junctions; these tight junctions regulate movement of solutes and ions
      through the paracellular space. CLDN4 is also a differentiation marker and is
      believed to indicate an epithelial phenotype. However, the role of CLDN4 in
      laryngeal squamous carcinoma is still unclear. Here, we showed that CLDN4
      expression was down-regulated in laryngeal squamous carcinoma tissues and
      negatively correlated with methyl-CpG-binding protein 2. In addition, CLDN4 was
      hypermethylated in HEp-2 cells. DNA demethylation of CLDN4 by 5-aza-2'
      deoxycytidine suppressed migration and invasion of HEp-2 cells, whereas CLDN4
      silencing restored the migration and invasion of HEp-2 cells. Therefore, CLDN4
      plays a key role in laryngeal squamous carcinoma progression.

PMID- 29447922
TI  - Regional lymph node sampling in lung carcinoma: a single institutional and
      national database comparison.
AB  - Assessing regional lymph node metastasis is a key component of lung carcinoma
      staging and prognostication. Recent guidelines have suggested a quality metric of
      10 total regional lymph nodes sampled with each stage I-II primary lung carcinoma
      resection. However, the extent of mediastinal lymph node sampling remains
      controversial. We assessed factors contributing to regional lymph node counts and
      effect on overall patient survival in an institutional cohort of 888 cases and
      the Surveillance, Epidemiology, and End Results national cancer registry (10 856
      cases). The distribution of total lymph node counts in lobectomy and
      pneumonectomy cases was variable with a median of 10 and an interquartile range
      of 7 to 14. Multiple clinical and pathologic factors correlated with total
      regional node counts. Total lymph node counts of at least 10 in the institutional
      cohort did not correlate with significant differences in overall survival as
      compared with node counts of less than 10 (P = .38). In the Surveillance,
      Epidemiology, and End Results database, although 0 regional lymph nodes were
      correlated with reduced overall survival (hazard ratio, 1.47; P < .01), no
      significant difference was detected for 1 to 9 versus at least 10 nodes (P = .8).
      In conclusion, lymph node counts for primary lung carcinoma are driven by
      surgical, pathologic, and biologic variability. We find no evidence for a
      meaningful quality metric of 10 total regional lymph nodes at the institutional
      and national registry levels.

PMID- 29447923
TI  - The significance of tumor budding in T1 colorectal carcinoma: the most reliable
      predictor of lymph node metastasis especially in endoscopically resected T1
      colorectal carcinoma.
AB  - Endoscopic resection is widely recognized as a first-line treatment for T1
      colorectal cancers (CRC), although additional surgical intervention may be
      indicated based on the risk of lymph node (LN) metastasis. However, risk factors
      for LN metastasis in T1 CRC not fully established. We investigated the
      clinicopathological features of T1 CRC and evaluated their association with lymph
      node metastasis in 133 cases of T1 CRC, consisting of 87 cases with first-line
      endoscopic resection (EMR) followed by additional surgery and 46 cases with
      primary surgical resection. Among the total 133 cases, 16 cases (12.0%) showed LN
      metastasis; 13 cases (13/16, 81.25%) were included in endoscopic resection
      cohort. These were all of the non-pedunculated gross type and most of LN+ tumors
      invaded submucosa over 1000 MUm (surgical cohort versus endoscopic resection
      cohort; 3 versus 11). However, there was no statistical difference in the depth
      of submucosal invasion between the LN+ and LN- in both surgical cohort (2799.42
      MUm +/- 401.56 versus 3000.00 MUm +/- 721.69, P = .897) and endoscopic resection
      cohort (2066.55 MUm +/- 142.96 versus 2305.77 MUm +/- 345.62, P = .520).
      Conversely, presence of and a higher number of tumor budding foci were associated
      with an increase in the incidence of LN metastasis in both cohort (P < .0001).
      Positive resection margins as well as absence of adenoma component were also an
      independent predictive factor for lymph node metastasis in 87 cases with first
      line endoscopic resection followed by additional surgery. We found that tumor
      budding was the most reliable LN metastasis predictor in T1 CRC in both
      surgically resected and endoscopic resection specimens.

PMID- 29447924
TI  - New prostate cancer grade grouping system predicts survival after radical
      prostatectomy.

PMID- 29447925
TI  - DJ-1 is a useful biomarker for invasive extrahepatic cholangiocarcinoma.
AB  - We have previously reported that DJ-1 protein is up-regulated in
      cholangiocarcinoma compared with non-neoplastic epithelium of the bile duct in a
      study using liquid-chromatography mass spectrometry-based proteomics. The aim of
      this study was to clarify whether DJ-1 expression offers a biomarker for patients
      with invasive extrahepatic cholangiocarcinoma (EHCC) who undergo surgical
      resection with curative intent. Positive immunohistochemical (IHC) staining of DJ
      1 was significantly more frequent in the cytoplasm of 96 invasive EHCCs (n = 28,
      29.2%) than in that of 66 non-neoplastic epithelial lesions adjacent to invasive
      EHCC (n = 7, 10.6%; P = .006). No significant difference in clinicopathological
      features was evident between invasive EHCC patients with negative (n = 68) and
      positive (n = 28) IHC staining. However, negative IHC staining for DJ-1 in
      cytoplasm was selected as an independent risk factor for adverse prognosis on
      multivariate analysis (P = .004, hazard ratio 2.13, 95% confidence interval 1.28
      3.57). Serum levels of DJ-1 in 16 invasive EHCC patients with metastasis were
      compared with 12 invasive EHCC patients without metastasis. Serum levels of DJ-1
      tended to be higher in 16 patients with metastasis (median, 40.9 ng/ml) than in
      12 patients without (27.6 ng/ml, P = .137). In addition, patients with high serum
      levels (>= 40 ng/ml) of DJ-1 tended to have metastasis more frequently than those
      without (P = .054, Fisher's exact test). We concluded that IHC staining pattern
      and serum level of DJ-1 in patients with invasive EHCC might be predictive of
      prognosis and metastasis, respectively.

PMID- 29447927
TI  - Impact of exposure factor selection on deterministic consumer exposure
      assessment.
AB  - Deterministic exposure assessment has uncertainty about the selection of input
      parameters on the resulting estimates. The purpose of this study was to compare
      inhalation exposures estimated by a specific percentile of each of the three
      exposure factors in deterministic assessment with population exposure. Exposure
      to nine household care products, namely a deodorizer, six cleaning products, and
      two disinfectants were investigated. The population exposures were individually
      calculated for three exposure factors (frequency of use, amount of use, and
      duration of use) from an existing database of 3333 participants representing the
      national population. Deterministic exposure assessment was conducted according to
      various percentiles of exposure factors. 99th percentiles of population exposure
      in all nine consumer products were 1.3-2.4 times greater than the 95th
      percentiles. Inhalation exposures based on the 75th percentiles of each of the
      three exposure factors in deterministic assessment were much lower than the 95th
      percentiles of the population exposure. Deterministic exposure estimates using
      85th to 99th percentiles of each of the three exposure factors were closer to the
      95th percentiles of the population exposure. We concluded that exposure factors
      in deterministic assessment should be greater than the 75th percentile to more
      precisely estimate exposure of at-risk groups.

PMID- 29447926
TI  - The role of physical activity enjoyment in the pathways from the social and
      physical environments to physical activity of early adolescent girls.
AB  - Most girls experience a notable decline in physical activity (PA) in early
      adolescence, increasing their risk for harmful health outcomes. Enjoyment for PA
      (i.e., positive feelings toward PA) is a determinant of PA among girls during
      adolescence and sustained PA throughout adulthood. Previous studies recommended
      increasing girls' PA enjoyment in order to increase their PA, but did not include
      environmental-level strategies for how families, schools, or communities do this.
      To gain insight on such strategies, this study examines the role of PA enjoyment
      as a mediator of social and physical environments to moderate-to-vigorous
      intensity PA of early adolescent girls. Cross-sectional, secondary analyses,
      using structural equation modeling, were conducted on a U.S. national dataset of
      1721 sixth grade girls from the Trial of Activity for Adolescent Girls in 2003.
      Mediation model fit parameters included chi2 (292, N = 1721) = 947.73 p < 0.001,
      CFI = 0.95, RMSEA = 0.04 (90% CI = 0.03, 0.04), and SRMR = 0.037 suggesting
      overall good fit. There were no indirect effects on PA through PA enjoyment from
      the social or physical environmental factors. To PA, there were significant
      direct effects only from social support from friends (beta = 0.15, CI = 0.09,
      0.22). To PA enjoyment, there were significant direct effects from social support
      from family (beta = 0.15, CI = 0.08, 0.23), school climate (teachers beta = 0.15,
      CI = 0.10, 0.21 and boys beta = 0.15, CI = 0.09, 0.20), and neighborhood
      environment (beta = 0.10, CI = 0.04, 0.17). The findings of this study identified
      several direct effects of the social and physical environment on PA enjoyment
      that can begin to inform environmental-level strategies for increasing PA
      enjoyment among early adolescent girls.

PMID- 29447928
TI  - The use of polysulfated polysaccharides heparin like compounds,
      glycosaminoglycans and Vitamin B17 as a possible treatment for prostate cancer.
AB  - Prostate cancer is impacting many men globally. It is a disease that has no
      effective treatment is available in the market. The understanding of the
      biophysical and biochemical aspects of the disease and the mechanism that allow
      it to metastasize is key to finding an effect treatment. Maintenance or
      pretreatment drug as well as a post treatment drug can be effective to avoid or
      delay the disease from appearing. The polysaccharides and monosaccharides
      polymers combined with vitamins can be the ingredient to developing the
      treatment. There are many evidences that investigators examined the individual
      components of the therapy proposed but never a combination of all these
      therapies. The one item that is not discussed is how to formulate the ingredient
      into an effective form which is a proprietary work being conducted currently.
      Nevertheless, the hypothesis seems reasonable to us and worth sharing with the
      scientific community.

PMID- 29447929
TI  - A complex systems approach to cancer prevention.
AB  - Cancer incidence continues to be a major health problem possibly because cancer
      is a complex system comprising many agents that interact in a non-linear manner
      resulting in many possible outcomes. The degree of complexity of a cancer system
      could be vast involving multiple endogenous and exogenous agents interacting with
      the over 10 trillion cells comprising the body. It is hypothesized that the
      practical management of this complexity may be a key to cancer prevention and
      possibly treatment. But the management and resolution of such an immensely
      complex system is difficult and may require a multidisciplinary approach
      including physics, biology, biochemistry and medical science. Research such as in
      systems biology involving large data sets may offer resolution in time, but the
      scale of the task is daunting. In evaluating the hypothesis, this paper proposes
      a method of resolution of the complex cancer system through a proxy in the form
      of the vital body system, energy balance, involved in several cancer processes.
      Although I suggest that the energy balance system is itself complex, it may
      permit access to factors that may be used in limiting cancer initiation. Meta
      analysis related to factors of blood sugar, inflammation, stress and immune
      response reveal that they could be likely candidates for management. Analysis
      also reveals certain devices that may give practical effect to these management
      options. Due to the inherent complexity of a cancer system, multiple devices may
      need to be applied in a combination. The analysis suggests that the low-risk and
      low-cost devices metformin, vitamin D and vitamin C, may prove to be suitable for
      use as a practical cancer prevention strategy. If the presented hypothesis is
      correct, a practical method for prevention or management of cancer may be
      possible. A trial to test the hypothesis is proposed.

PMID- 29447930
TI  - Linked help from bacterial proteins drives autoantibody production in small
      vessel vasculitis.
AB  - The small vessel vasculitides granulomatosis with polyangiitis (GPA) and
      microscopic polyangiitis are associated with autoantibodies to neutrophil
      cytoplasm antigens (ANCA), principally proteinase-3 (PR3) and myeloperoxidase
      (MPO). There is an association between GPA and nasal carriage of Staphylococcus
      aureus. The recent finding that S. aureus produces proteins that bind tightly to
      and block the function of both PR3 and MPO suggests a mechanism for ANCA
      formation. The bacterial protein-autoantigen conjugate is recognised by B cells
      with ANCA specificity, internalised, and the bacterial protein processed and
      presented to T cells with specificity for bacterial peptides. The T cell can then
      provide help to the B cell, allowing class switching, affinity maturation and the
      production of pathogenic ANCA. This mechanism predicts that T cells with this
      specificity will be found in patients, and that the bacterial protein-autoantigen
      conjugate will be particularly efficient at eliciting ANCA production.

PMID- 29447931
TI  - Impulsive mechanisms influencing relapse in alcohol drinking.
AB  - Impulsivity has been related to different features of addictive behaviors.
      Growing data, generated in separated lines of research, suggest that different
      processes underlying impulsivity are associated to relapse in alcohol drinking.
      Considering the evidence, relapse can be understood as an impulsive choice or as
      an impulsive action. In the first case, the return to drinking behavior is a
      consequence of insensitive to delayed consequence, that is, to the discounting of
      delayed rewards. In the second case, relapse is a consequence of failures to
      inhibit prepotent responses. Nevertheless, conditions that control the action of
      each mechanism or their interaction to influence relapse still unknown. We
      hypothesize that both mechanisms interact to produce relapse depending on framing
      effects, the moments of a drinking episode or context. The implication of the
      hypothesis is that relapse prevention strategies need to reduce discounting rate,
      but also to increase behavioral inhibition in the presence of cues related to
      alcohol.

PMID- 29447932
TI  - Determining the venous oxygen reservoir: A novel, hypothetical approach to
      titration of supplemental oxygen in preterm newborns.
AB  - While normal oxygen saturation is commonly thought to be a marker of normal
      oxygenation, cutaneous saturation does not account for the sufficiency of oxygen
      within each cell or that of the system overall. Rather, cutaneous oximetry simply
      defines the saturation of haemoglobin (Hb) with oxygen in a pulsatile vessel.
      Assessment of sufficiency is best determined by measurement of the amount of
      oxygen left over following aerobic respiration. This left over oxygen is 'stored'
      on Hb in the venous compartment and can be calculated as the venous oxygen
      content. We hypothesize that the development of a venous oxygen content or
      saturation reference range in a group of well, uninjured very preterm newborns
      and subsequent application, in a randomised trial, with a structural, functional
      and molecular outcome will resolve the method for assessment of oxygen
      sufficiency in preterms by demonstrating both clinical safety and effectiveness.
      This method could be subsequently used for titration of supplemental oxygen.

PMID- 29447933
TI  - Ultrasound-guided percutaneous electrolysis: A new therapeutic option for mammary
      fistulas.
AB  - Mammary fistula (MF) is a recurrent condition characterised by the draining of
      abscesses around the areola. The best management for MF remains challenging.
      Moreover, the main problem is the high recurrence rate of this disease. MF is
      considered a chronic process. The percutaneous electrolysis (PE) technique
      involves the application of a galvanic current with an ultrasound-guided needle
      to induce ablation and repair of the affected tissue. Good results have been
      obtained with PE in chronic tendinopathies. Below we present a hypothesis that PE
      may be a new therapeutic option for MF.

PMID- 29447934
TI  - Mismatch between GLUTs and glucose levels causes neuronal damage during glucose
      fluctuations.
AB  - Abnormal glucose levels damage the central nervous system, especially in case of
      rapid fluctuations. Even a single episode of glucose reperfusion can result in
      overt impairment of neurons. Oxidative stress plays an important role in this
      process, sharing properties with the pathophysiologic changes of glucose
      neurotoxicity. Glucose transporters (GLUTs) located in the brain are involved in
      direct glucose uptake by neurons. Instead of being insulin-sensitive, these
      transporters are regulated by glucose levels in the extracellular fluid,
      increasing their expression while glucose levels fall, to absorb more glucose.
      Therefore, we hypothesized that mismatch between altered GLUTs and sudden glucose
      level changes is responsible for neuronal damage during glucose fluctuations.
      Modulating hypoglycemia by increasing blood glucose slowly may improve the
      neurological outcomes of hypoglycemia.

PMID- 29447935
TI  - Biofilms busters to improve the detection of Borrelia using PCR.
AB  - Lyme disease is an affection caused by a spirochete infection called Borrelia
      Burgdorferi which may harbor a varied and misleading clinical symptomatology. The
      serology tests commonly used for diagnosis show a wide sensitivity varying from
      34% to 70,5%, leaving many infected patients with false negative tests.
      Alternative techniques such as polymerase chain reaction (PCR) could be helpful
      but not conclusive enough. Using biofilm busters, such as stevia and
      serratiopeptidase, could lead to bacterial blood release, thus increasing the
      spirochete load, making PCR test more sensitive, thus improving the patient's
      diagnosis and management.

PMID- 29447936
TI  - Inducing hypertrophic effects of type I skeletal muscle fibers: A hypothetical
      role of time under load in resistance training aimed at muscular hypertrophy.
AB  - An emerging body of evidence is starting to suggest that the hypertrophy of
      skeletal muscle fibers might be load specific. In other words, it may be that
      resistance training with high loads (i.e., >=60% of 1 repetition maximum [RM])
      emphasizes a greater growth of type II muscle fibers, while resistance training
      with low loads (i.e., <60% of 1RM) might primarily augment hypertrophy of type I
      muscle fibers. Type I and type II muscle fibers possess certain distinct
      characteristics, with type II muscle fibers having faster calcium kinetics,
      faster shortening velocities, and ability to generate more power than type I
      muscle fibers. Alternatively, compared to type II fibers, type I muscle fibers
      have a higher oxidative capacity and a higher fatigue threshold. Due to the lower
      fatigability of type I muscle fibers, it may be hypothesized that a greater time
      under load is necessary to stimulate an accentuated growth of these fibers. An
      increase in time under load can be achieved when training with lower loads (e.g.,
      30% of 1RM) and to momentary muscular failure. The present paper discusses the
      hypothesis that a greater hypertrophy of type I muscle fibers may be induced with
      low load resistance training.

PMID- 29447937
TI  - Splenectomy may have more complications than currently proven.
AB  - The spleen has been one of the least understood major organs for centuries. Its
      significance is relatively well-known today but it seems that all aspects of its
      activities are not fully understood. Persian medicine (PM) has special views on
      the function of spleen; many side effects were reported in PM due to spleen
      dysfunction. On the other hand nowadays splenectomy as a treatment strategy is
      recommended for some disorders and increasing risk of infections is considered as
      the most important long term side effect of that. In this study, we hypothesize
      that splenectomy may have more side effects than currently proven. According to
      PM, spleen is in close connection with liver, cardiovascular system, stomach,
      bone, brain and skin, and that is why any kind of spleen dysfunction leads to
      change in blood viscosity, appetite and bone strength, liver dysfunction, mood
      and skin disorders, cancer formation and fever. Considering this viewpoint it can
      be hypothesized such side effects may also occur after splenectomy. Proven
      complications of splenectomy include hypercoagulated state, cardiovascular events
      and infectious diseases but there is also some evidence about increased risk of
      cancer, skin disease like systemic lupus erythematosus, mood disorder such as
      depression, defective bone formation and impairment of immunity which can be
      considered as different levels of evidence to confirm the hypothesis. But for
      some others such as changes in appetite, there are no studies let alone
      convincing evidence. Future research about theses possible complications may lead
      to novel results.

PMID- 29447938
TI  - Hypothesis: Is there a link between the immune response to Human Herpes Virus
      type 6Alpha (HHV-6Alpha) infection and the interaction network (interactome) of
      the genes encoding the CTSS, PTX3, CHI3L1, Mx1, CXCL16, BIRC3 and BST2 proteins?
AB  - Human Herpes Virus type 6 (HHV-6) is a ubiquitous virus consisting of two viral
      species, HHV-6A and HHV-6B that have been associated with numerous and diverse
      pathologies. As many other viruses HHV-6 modulates the apoptotic machinery of its
      host to subvert immune response to infection, yet the exact mechanisms behind
      this process remain under investigation. The genes encoding the CTSS, PTX3,
      CHI3L1, Mx1, CXCL16, BIRC3 and BST2 proteins have been linked to HHV-6Alpha
      related neurologic diseases whilst also associated with apoptosis. This study
      aimed at the identification and functional analysis of the gene interaction
      network (interactome) of CTSS-PTX3-CHI3L1-Mx1-CXCL16-BIRC3-BST2 so as to evaluate
      the hypothesis of a probable link between the latter and host's immune response
      to HHV-6A infection.

PMID- 29447939
TI  - The cardiovascular robustness hypothesis: Unmasking young adults' hidden risk for
      premature cardiovascular death.
AB  - An undetected high risk for premature death of cardiovascular disease (CVD) among
      individuals with low-to-moderate risk factor levels is an acknowledged obstacle
      to CVD prevention. In this paper, we present the hypothesis that the
      vasculature's robustness against risk factor load will complement conventional
      risk factor models as a novel stratifier of risk. Figuratively speaking,
      mortality risk prediction without robustness scoring is akin to predicting the
      breaking risk of a lake's ice sheet considering load only while disregarding the
      sheet's bearing strength. Taking the cue from systems biology, which defines
      robustness as the ability to maintain function against internal and external
      challenges, we develop a robustness score from the physical parameters that
      comprehensively quantitate cardiovascular function. We derive the functional
      parameters using a recently introduced novel system, VascAssist 2 (iSYMED GmbH,
      Butzbach, Germany). VascAssist 2 (VA) applies the electronic-hydraulic analogy to
      a digital model of the arterial tree, replicating non-invasively acquired pule
      pressure waves by modulating the electronic equivalents of the physical
      parameters that describe in vivo arterial hemodynamics. As the latter is also
      subject to aging-associated degeneration which (a) progresses at inter
      individually different rates, and which (b) affects the biomarker-mortality
      association, we express the robustness score as a correction factor to calendar
      age (CA), the dominant risk factor in all CVD risk factor models. We then propose
      a method for the validation of the score against known time-to-event data in
      reference populations. Our conceptualization of robustness implies that risk
      factor-challenged individuals with low robustness scores will face preferential
      elimination from the population resulting in a significant robustness-CA
      correlation in this strata absent in the unchallenged stratum. Hence, we also
      present an outline of a cross-sectional study design suitable to test this
      hypothesis. We finally discuss the objections that may validly be raised against
      our robustness hypothesis, and how available evidence encourages us to refute
      these objections.

PMID- 29447940
TI  - The relationship between plasma vascular endothelial growth factor and
      erythrocyte 2,3-bisphosphoglycerate: The putative role of chronic hypoxia.
AB  - The non-invasive assessment of chronic tissue hypoxia is difficult. Pulse
      oximetry only allows the peripheral oxygen saturation to be measured, while the
      detection of hyperlactataemia needs to take into account the fact that the
      accumulation of lactic acid may result from several causes other than prolonged
      tissue hypoxia. Arterial blood oxygen measurement is invasive and often does not
      give a good indication of the level of tissue hypoxia. Other suggested methods
      include the use of positron emission tomography, magnetic resonance T2*
      relaxation time measurement, photoacoustics and high-frequency ultrasound. Tissue
      hypoxia leads to increased levels of hypoxia-inducible factor-1alpha, which in
      turn upregulates VEGFA, leading to increased levels of vascular endothelial
      growth factor (VEGF), which promote angiogenesis. Hypoxia lasting for more than a
      few hours is associated with increased synthesis in erythrocytes of 2,3
      bisphosphoglycerate (BPG), a powerful regulator of the allosteric properties of
      haemoglobin, via the Rapoport-Luebering phosphoglycerate cycle. We therefore
      hypothesised that plasma VEGF and erythrocyte BPG levels should be positively
      correlated. Venous blood samples from 34 patients (18 male, mean age (standard
      error) 43.4 (3.2) y) were analysed; plasma VEGF was measured using an enzyme
      linked immunosorbent assay while the erythrocyte BPG was assessed by quantitative
      Fourier transform infrared spectrometry following gel electrophoresis. The
      Pearson product-moment correlation between the two variables was 0.622 (p <
      0.0001). Based on our findings, we suggest that it may be useful to measure both
      erythrocyte BPG and plasma VEGF, together, when assessing chronic hypoxia;
      elevated levels of both are likely to indicate hypoxia.

PMID- 29447941
TI  - Eliminated respiration-coupled oscillations in the brain as a possible link
      between adenotonsillar hypertrophy and cognitive impairment.

PMID- 29447942
TI  - Pathogenesis of idiopathic retinal vasculitis, aneurysms, and neuroretinitis
      (IRVAN) or 'idiopathic retinal arteriolar aneurysms (IRAA)' with macular star.

PMID- 29447943
TI  - Novel mutant of Escherichia coli asparaginase II to reduction of the glutaminase
      activity in treatment of acute lymphocytic leukemia by molecular dynamics
      simulations and QM-MM studies.
AB  - L-Asparaginases (ASNase) belong to a family of amidohydrolases, have both
      asparaginase and glutaminase activity. Acute lymphocytic leukemia (ALL) is an
      outrageous disease worldwide. Bacterial ASNase has been used for the treatment of
      ALL. Glutaminase activity of enzyme causes some side effect and it is not
      essential for anticancer activity. The aim of this study was engineering of
      Escherichia coli asparaginase II to find a mutant with reduced glutaminase
      activity by molecular docking, molecular dynamics (MD) and QM-MM (Quantum
      mechanics molecular dynamics) simulations. Residues with low free energy of
      binding to Asn and high free binding energy to Gln were chosen for mutagenesis.
      Then, a mutant with higher glutaminase free binding energy was selected for
      further studies. Additionally, the MD simulation and QM-MM computation of wild
      type (WT) were employed and the selected mutated ASNase were analyzed and
      discussed. Our data showed that V27T is a good candidate to reduction the
      glutaminase activity, while has no remarkable effect on asparaginase activity of
      the enzyme. The simulation analysis revealed that V27T mutant is more stable than
      WT and mutant simulation was successful completely. QM-MM results confirmed the
      successfulness of our mutagenesis.

PMID- 29447944
TI  - Activation of liver X receptor beta-enhancing neurogenesis ameliorates cognitive
      impairment induced by chronic cerebral hypoperfusion.
AB  - Chronic cerebral hypoperfusion (CCH), a leading cause of various cerebrovascular
      diseases, leads to cognitive dysfunction due to neuron loss and impaired
      neurogenesis. Liver X receptors (LXRs), including LXRalpha and LXRbeta isoforms,
      are crucial for cholesterol metabolism, synaptic plasticity as well as
      neurogenesis. However, it is not clear the potential roles of LXRs in the
      pathogenesis of cognitive impairment induced by CCH. In this study, we
      demonstrated that LXRbeta expression decreased in hippocampus of CCH mice.
      GW3965, a synthetic dual agonist for both LXRalpha and LXRbeta, ameliorated
      impairment of learning and memory in CCH mice by promoting neuronal survival and
      neural stem cells (NSCs) proliferation in dentate gyrus (DG) of CCH mice. The
      proliferative effects of GW3965 were further confirmed in cultured neural
      progenitor cells (NPCs) and showed in a concentration-dependent manner. Moreover,
      GW3965 phosphorylated protein kinase B (Akt) at Ser473 in a time- and
      concentration-dependent manner in NPCs. Furthermore, both LY294002, an inhibitor
      for phosphoinositide-3-kinase (PI3K), and short hairpin RNAs for LXRbeta
      knockdown, abrogated GW3965-induced Akt phosphorylation, and therefore abolished
      GW3965-mediated proliferation-promoting of NPCs. All the data suggested that
      GW3965 ameliorated impaired cognitive functions in CCH by promoting NSC
      proliferation through PI3K/Akt pathway followed LXRbeta activation. This study
      correlates a deficit of LXRbeta in cognitive dysfunction in CCH with impaired
      neurogenesis in hippocampus, and LXRs may serve as a potential therapeutic target
      for chronic cerebral ischemia.

PMID- 29447945
TI  - Salmeterol, agonist of beta2-aderenergic receptor, prevents systemic inflammation
      via inhibiting NLRP3 inflammasome.
AB  - beta2-Aderenergic receptor (beta2AR) agonist, Salmeterol exhibits anti
      inflammatory activities. However, the inhibitory effects of Salmeterol on
      inflammasome activation are elusive and the underlying mechanisms need to be
      explored. In this study, we established inflammatory model in primary bone marrow
      derived macrophages (BMDM) from C57BL/6J mice and beta-arrestin2 knockout (beta
      arrestin2-/-) mice in vitro. In vivo study by LPS intraperitoneally (i.p.) in
      C57BL/6J mice was carried out to ascertain its roles in systemic inflammation. We
      found that Salmeterol (10-10 M-10-7 M) prevented the cleavage of caspase-1 and
      the activation of NLRP3 inflammasome, reduced the release of pro-inflammatory
      cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) in vitro. Blockade of adenosine3',5'cyclic monophosphate (cAMP)/protein
      kinase A (PKA) pathway with cAMP or PKA inhibitors inhibited anti-inflammatory
      effects of Salmeterol only at 10-7 M. Depletion of beta-arrestin2 compromised the
      inhibitory effects of Salmeterol at both 10-10 M and 10-7 M. Salmeterol increased
      the interaction of beta-arrestin2 and NLRP3. In vivo study showed that Salmeterol
      decreased the serum concentrations of pro-inflammatory cytokines IL-1beta and TNF
      alpha, blocked cleavage of caspase-1 and release of IL-1beta in BMDM. These
      findings imply that Salmeterol at low concentrations (10-10 M-10-7 M) shows anti
      inflammatory effect via inhibiting NLRP3 inflammasome. The underlying mechanisms
      is dosage-dependent: Salmeterol at 10-10 M shows anti-inflammatory effects
      through beta-arrestin2 pathway, and 10-7 M Salmeterol inhibits inflammation via
      both classical G-protein coupled receptor (GPCR)/cAMP pathway and beta-arrestin2
      pathway. These results provide new ideas for the future treatment of systemic
      inflammation and other inflammatory diseases.

PMID- 29447946
TI  - Bladder Re-augmentation in Classic Bladder Exstrophy: Risk Factors and
      Prevention.
AB  - OBJECTIVE: To characterize the causes of re-augmentation in patients with classic
      bladder exstrophy (CBE). METHODS: A prospectively maintained institutional
      database of 1327 exstrophy-epispadias complex patients was reviewed for patients
      with CBE who underwent more than 1 augmentation cystoplasty (AC) procedure. Data
      regarding bladder capacities, complications following AC, and reasons for re
      augmentation were evaluated. RESULTS: A total of 166 patients with CBE underwent
      AC. Of these, 67 (40.4%) were included in the control group and 17 (10%) patients
      underwent a re-augmentation. There were several indications for re-augmentation
      including continued small bladder capacity (17 of 17), inadequate bladder necks
      (8 of 17), failed rattail augmentation (2 of 17), stomal incontinence (1 of 17),
      a urethrocutaneous fistula (1 of 17), and an hourglass augmentation (1 of 17). Of
      note, 5 of the 17 patients (29%) had a re-augmentation procedure with a ureteral
      reimplantation. The sigmoid colon was the most commonly used bowel segment in the
      failed initial AC (8 patients), whereas the ileum was the most commonly used
      segment during re-augmentation (12 patients). In the re-augmentation cohort, the
      mean amount of bowel used during the first AC procedure was 12 cm (standard
      deviation [SD] 3.6) compared with 19 cm (SD 5.0) during re-augmentation. The mean
      amount of bowel used for control group augmentations was 20.8 cm (SD 4). The mean
      re-augmentation preoperative bladder capacity of 100 mL (SD 60) immediately
      increased after re-augmentation to 180.8 mL (SD 56.4) (P = .0001). CONCLUSION:
      Bladder re-augmentation is most commonly required in the setting of a small
      bladder capacity after an initial AC, when an insufficient amount of bowel is
      used during the first AC procedure.

PMID- 29447947
TI  - 80-W GreenLight Laser Vaporization Versus Transurethral Resection of the Prostate
      for Treatment of Benign Prostatic Obstruction: 5-Year Outcomes of a Single-center
      Prospective Randomized Trial.
AB  - OBJECTIVE: To assess long term functional and safety follow-up data after 80-W
      GreenLight photoselective vaporization (GL PV) of the prostate and transurethral
      resection of the prostate (TURP). MATERIALS AND METHODS: Prospective randomized
      trial at a single tertiary referral center (Geneva, Switzerland). Patients were
      recruited in the outpatient clinic if they met the criteria for surgical
      treatment of benign prostatic obstruction. At baseline, 238 patients were treated
      either with the 80-W GL PV or monopolar TURP. After 5 years, data were available
      from 105 patients: 44 GL PV patients and 61 TURP patients. The primary outcome
      measure was the International Prostate Symptom Score (IPSS). Secondary outcome
      measures included maximum urinary flow rate (Qmax), postvoidal residual (PVR) and
      reoperation rate. Statistical analyses were performed using Stata 14 (StataCorp).
      RESULTS: After 5 years of follow-up, mean improvements in International Prostate
      Symptom Score, postvoidal residual and maximum urinary flow rate were similar in
      both groups. The re-treatment rate was 14.3% in the GL PV group vs 11.9% in the
      TURP group (P = .9). CONCLUSION: Noninferiority of the GL PV to TURP was
      confirmed in all functional and safety outcomes at 5-year follow-up. GL-PV could
      be a safe surgical alternative for patients suffering from benign prostatic
      obstruction.

PMID- 29447948
TI  - Roles of Ihh signaling in chondroprogenitor function in postnatal condylar
      cartilage.
AB  - Condylar articular cartilage in mouse temporomandibular joint develops from
      progenitor cells near the articulating surface that proliferate, undergo
      chondrogenesis and mature into hypertrophic chondrocytes. However, it remains
      unclear how these processes are regulated, particularly postnatally. Here we
      focused on the apical polymorphic layer rich in progenitors and asked whether the
      phenotype and fate of the cells require signaling by Indian hedgehog (Ihh)
      previously studied in developing long bones. In condyles in newborn mice, the
      apical polymorphic/progenitor cell layer was ~10 cell layer-thick and expressed
      the articular matrix marker Tenascin-C (Tn-C), and the underlying thick cell
      layer expressed Tn-C as well as the chondrogenic master regulator Sox9. By 1
      month, condylar cartilage had gained its full width, but became thinner along its
      main longitudinal axis and displayed hypertrophic chondrocytes. By 3 months,
      articular cartilage consisted of a 2-3 cell layer-thick zone of superficial cells
      and chondroprogenitors expressing both Tn-C and Sox9 and a bottom zone of
      chondrocytes displaying vertical matrix septa. EdU cell tracing in juvenile mice
      revealed that conversion of chondroprogenitors into chondrocytes and hypertrophic
      chondrocytes required about 48 and 72 h, respectively. Notably, EdU injection in
      3 month-old mice labeled both progenitors and maturing chondrocytes by 96 h.
      Conditional ablation of Ihh in juvenile/early adult mice compromised
      chondroprogenitor organization and function and led to reduced chondroprogenitor
      and chondrocyte proliferation. The phenotype of mutant condyles worsened over
      time as indicated by apoptotic chondrocyte incidence, ectopic chondrocyte
      hypertrophy, chondrocyte column derangement and subchondral bone deterioration.
      In micromass cultures of condylar apical cells, hedgehog (Hh) treatment
      stimulated chondrogenesis and alkaline phosphatase (APase) activity, while
      treatment with HhAntag inhibited both. Our findings indicate that the
      chondroprogenitor layer is continuously engaged in condylar growth postnatally
      and its organization and functioning depend on hedgehog signaling.

PMID- 29447949
TI  - Protective effects of Alpinae Oxyphyllae Fructus extracts on lipopolysaccharide
      induced animal model of Alzheimer's disease.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Alpinae Oxyphyllae Fructus (AOF) with warming and
      tonifying the kidney and spleen, anti-salivation, anti-polyuria and anti-diarrhea
      functions is the dried ripe fruits of Alpinia oxyphylla Miq. (Zingiberaceae). As
      a traditional Chinese medicine, its application history is very long. AIMS OF THE
      STUDY: The purpose of our study is to investigate the effects of different
      solvent extracts from AOF on lipopolysaccharide (LPS)-induced animal model of
      Alzheimer's disease (AD) to elucidate the traditional medical theories with
      modern pharmacological methods and provide a reference for further clarifying its
      active components and mechanisms. MATERIALS AND METHODS: The method of stepwise
      screening was adopted in this paper. The animals were divided into 9 groups,
      including control (CT) group, model (MD) group, donepezil (DPZ) group, total
      extract (TT) group, petroleum ether extract (PE) group, chloroform extract (CF)
      group, ethyl acetate extract (EA) group, n-butanol extract (NB) group and water
      extract (WT) group. The anti-amnesic effects of different solvent extracts from
      AOF were measured in LPS-induced memory deficits mice by Y maze test and Morris
      water maze (MWM) test. Hematoxylin eosin (HE) staining was applied to observe
      pathological changes in hippocampus and cerebral cortex tissue of different
      groups. Biochemical indicators including ionized calcium-binding adaptor molecule
      1 (IBA-1), interleukin beta 1 (IL-1beta), Abeta1-42 and hyperphosphorylated tau
      proteins (p-tau) in hippocampus and cortex after treatment with LPS were measured
      according to the manufacturer's instructions of ELISA kits. HPLC was used to
      evaluate the major components of different extracts. RESULTS: It was found that
      successive intragastric administration of AOF (360 mg/kg) extracts for 14 days
      showed different degrees of improvement on LPS-induced AD model as measured by Y
      maze test, Morris water maze test, and Histopathological examination. Moreover,
      the results of ELISA suggested petroleum ether (PE) extracts were worth
      recommending for inhibiting the high level of IBA-1, IL-1beta, Abeta1-42 and p
      tau in hippocampus and cortex after treatment with LPS. CONCLUSIONS: The present
      study demonstrated for the first time that AOF attenuated LPS-induced learning
      and memory impairment, which may be associated with its inhibitory effect on
      neuroinflammation, amyloids-beta (Abeta) deposition and p-tau. This research
      provided a theoretical basis for elucidating the traditional theory of AOF, and
      was also the stepping stone to the next step.

PMID- 29447950
TI  - Ethnobotanical and ethnomedicinal studies in Baluchi tribes: A case study in Mt.
      Taftan, southeastern Iran.
AB  - ETHNOBOTANICAL RELEVANCE: From ancient times, the applied use of herbs has been
      common among indigenous people throughout the world. The present survey is a
      regional ethnobotanical study of Baluchi tribes living in the Mt. Taftan area,
      Sistan and Baluchistan Province, southeastern Iran. The aim of this study was to
      document all traditional knowledge and analyze the medicinal plants used in area
      and also to identify significant plant species for future pharmacological study.
      MATERIALS AND METHODS: Local knowledge was obtained through semi structured and
      open interviews, in which 51 informants were interviewed. Data were analyzed with
      Informant Agreement Relative (IAR) and Frequency of Citation (FC) indices.
      RESULTS: A total number of 106 taxa of medicinal plants were collected from ten
      villages from the surrounding plains and highlands of Mt. Taftan, out of 446
      plant taxa collected or reported as native in the area. Most plants belong to the
      Irano-Turanian phytogeographical region in which Asteraceae (15%), Lamiaceae
      (11%), Fabaceae (8%), Rosaceae (7%), Apiaceae (7%) and Brassicaceae (5%) are
      those predominantly used. The regression analysis shows that families Apiaceae,
      Lamiaceae, Solanaceae and Rosaceae are more highly used as medicinal than species
      rich families such as Asteraceae and Fabaceae, which are the richest families in
      the Iranian flora. The highest FC was recorded for Artemisia spp. (41) and
      Berberis integerrima (40). The highest IAR Index was obtained for stings (0.86),
      followed by disorders in the circulatory system (0.7), dental problems (0.70) and
      injuries (0.69). Comparing our data with major ethnobotanical references in Iran
      revealed that medicinal applications of 34 taxa have not been cited, including
      Hyoscyamus malekianus, a local endemic plant using for ailments of toothache and
      worms. The toxicity of the endemic Semenovia suffruticosa is also reported.
      CONCLUSION: As a result of this study we conclude that Taftan area harbours many
      plant species for which indigenous knowledge provides a background of medicinal
      importance. The high percentage of medicinal plants proportional to the native
      flora is 23.8%, compared to the world percentage of 17.1%, is an indication of
      the rich knowledge and relationship of isolated Baluchi tribes living in Mt.
      Taftan to the local flora growing in their surroundings. This rich knowledge
      should be highly regarded as a cultural and ethnobotanical heritage. Furthermore,
      ethnobotanical results show some weak interrelation between Baluchi tribes living
      in Iran and Pakistan, probably because of a different flora and/or unfavourable
      environmental conditions and perhaps local conflicts which might have reduced
      active cultural exchange.

PMID- 29447951
TI  - Suction electrode recording in locus coeruleus of newborn rat brain slices
      reveals network bursting comprising summated non-synchronous spiking.
AB  - The brainstem locus coeruleus (LC) controling behaviors like arousal, sleep,
      breathing, pain or opioid withdrawal is an established model for spontaneous
      action potential synchronization. Such synchronous 'spiking' might produce an
      extracellular field potential (FP) which is a crucial tool for neural network
      analyses. We found using >=10 MUm tip diameter suction electrodes in newborn rat
      brainstem slices that the LC generates at ~1 Hz a robust rhythmic FP (rFP).
      During distinct rFP phases, LC neurons discharge with a jitter of +/-33 ms single
      spikes that summate to a ~200 ms-lasting population burst. The rFP is abolished
      by blocking voltage-gated Na+ channels with tetrodotoxin (TTX, 50 nM) or gap
      junctions with mefloquine (100 MUM) and activating MU-opioid receptors with [D
      Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin (DAMGO, 1 MUM). Raising superfusate K+ from 3
      to 7 mM either increases rFP rate or transforms its pattern to slower and longer
      multipeak bursts similar to those during early recovery from DAMGO. The results
      show that electrical coupling of neonatal LC neurons does not synchronize their
      spiking as previously proposed. They also indicate that both increased
      excitability (by elevated K+) and recovery from inhibition (by opioids) can
      enhance spike desynchronization to transform the population burst pattern. Both
      observations show that this gap junction-coupled neural network has a more
      complex connectivity than currently assumed. These new findings along with the
      inhibitory drug effects that are in line with previous reports based on single
      neuron recording point out that field potential analysis is pivotal to further
      the understanding of this brain circuit.

PMID- 29447952
TI  - Insulin enhances GABAA receptor-mediated inhibitory currents in rat central
      amygdala neurons.
AB  - Insulin, a pancreatic hormone, can access the central nervous system, activate
      insulin receptors distributed in selective brain regions and affect various
      cellular functions such as neurotransmission. We have previously shown that
      physiologically relevant concentration of insulin potentiates the GABAA receptor
      mediated tonic inhibition and reduces excitability of rat hippocampal CA1
      neurons. The central nucleus of the amygdala (CeA) comprises heterogeneous
      neuronal populations that can respond to hormonal stimulus. Using quantitative
      PCR and immunofluorescent labeling, we report that the mRNA and protein of the
      insulin receptor are abundantly expressed in the rat CeA. The insulin receptor
      mRNA is also detected in the CeA from post-mortem human brain samples.
      Furthermore, our whole-cell patch-clamp recordings show that the application of
      insulin (5 and 50 nM) selectively enhances the frequency and amplitude of
      spontaneous inhibitory postsynaptic currents (sIPSCs) in rat CeA neurons. Our
      findings reveal that GABAergic synaptic transmission is a target in the CeA for
      insulin receptor signaling that may underlie insulin modulation of emotion- and
      feeding-related behaviors.

PMID- 29447954
TI  - The inhibitory effect of levo-tetrahydropalmatine on the methamphetamine-induced
      spatial memory impairment in mice.
AB  - Methamphetamine (METH) administration results in addiction and memory impairment.
      Previous studies have suggested that levo-tetrahydropalmatine (l-THP), an
      alkaloid purified from the Chinese herb Corydalis, attenuates the behavioral
      changes induced by METH. Therefore, in this study, we explored whether l-THP
      could also protect against the METH-induced memory impairment examined using the
      Morris water maze (MWM). We found that low dose of METH (1.0 mg/kg) treated for
      20 consecutive days prior to the MWM experiment impaired spatial memory retention
      but not acquisition in mice. In addition, high dose of METH (10.0 mg/kg) treated
      during the spatial learning phase for five consecutive days impaired both the
      acquisition and retention of spatial memory. Moreover, both of these impairments
      induced by METH were reversed by l-THP treatment, indicating a potential
      protective role of l-THP in METH use.

PMID- 29447953
TI  - Dendrite growth and the effect of ectopic Rheb expression on cortical neurons.
AB  - Ras homology enriched in brain (Rheb) is a GTPase that activates the protein
      kinase mammalian Target of Rapamycin (mTOR). Rheb mutations cause intellectual
      delay and megalencephaly. mTOR hyperactivation causes a constellation of
      neurodevelopmental disorders called "mTOR-opathies" that are frequently
      accompanied by hyperexcitable cortical malformations. Cortical malformations
      within the anterior cingulate cortex (ACC) and somatosensory cortex (SSC)
      frequently colocalize with hyperexcitability. Although Rheb and mTOR are
      implicated in the formation of cortical lesions, seizure activity, and defects in
      neuronal migration, the contribution of Rheb to changes in neuron size and
      dendrite morphology is not well established. Here, in utero electroporation of
      the developing embryonic brain was used to assess soma and dendrite growth in ACC
      and SCC layer II/III neurons. We found that between P0 and P21, neuronal soma
      size increased by 50 and 122 percent in the ACC and SSC, respectively. The
      increased size was accompanied by an increase in the number of basal dendrites
      and enhanced dendrite complexity. As an indicator of the involvement of the mTOR
      pathway in neuron maturation, phosphorylation of the mammalian target of
      rapamycin (mTOR) substrate S6 was identified in migrating cortical neuroblasts
      and maturing neurons. Notably, ectopic expression of Rheb caused cortical
      malformations comprised of ectopically positioned cytomegalic neurons with
      dendrite hypertrophy. This study provides a direct comparison of neuron
      maturation across two cortical regions during development, provides evidence for
      mTOR pathway activity during neuron maturation, and demonstrates that ectopic
      Rheb expression without mutation is sufficient to induce cortical malformations
      with cytomegaly and dendrite hypertrophy.

PMID- 29447955
TI  - PTH (1-34) affects bone turnover governed by osteocytes exposed to fluoride.
AB  - Exposure to fluoride from environmental sources remains an overlooked, but
      serious public health risk. In this study, we looked into the role osteocytes
      play on the mechanism underlying fluoride induced osteopathology. We analyzed
      bone formation and resorption related genes generated by osteocytes that were
      exposed to varied doses of fluoride with and without PTH in vitro.
      Correspondingly, osteogenesis and osteoclastogenesis related genes were also
      investigated in rats exposed to fluoride for 8 weeks, and the PTH(1-34)was
      applied at the last 3 weeks to observe its role in regulating bone turnover upon
      fluoride treatment. The data in vitro indicated that fluoride treatment inhibited
      Sost expression of mRNA and protein and stimulated RANKL mRNA protein expression
      as well as the RANKL/OPG ratio in the primary osteocytes. Single PTH treatment
      played the similar role on expression of these genes and proteins. The PTH
      combined administration enhanced the action of fluoride treatment on RNAKL/OPG
      and SOST/Sclerostin. The up-regulation of RANKL and decreasing of Sost induced by
      fluoride and/or PTH treatment was validated in vivo and suggests that osteocytes
      are a major source of RANKL and Sost, both of which play essential roles in
      fluoride affecting osteogenesis and osteoclastogenesis. Expression of Wnt/beta
      catenin was up-regulated in both in vitro osteocytes treated with high dose of
      fluoride and bone tissue of rats in the presence of fluoride and PTH. In vivo,
      fluoride and single PTH stimulated bone turnover respectively, furthermore, PTH
      combined with low dose of fluoride treatment reinforced the osteogenesis and
      osteoclastogenesis genes expression, however, co-treatment of PTH reversed the
      effect of high dose of fluoride on osteogenesis and osteoclastogenensis related
      factors. In conclusion, this study demonstrated that osteocytes play a key role
      in fluoride activated bone turnover, and PTH participates in the process of
      fluoride modulating SOST/Sclerostin and RANKL expression.

PMID- 29447956
TI  - Pubertal chlorocholine chloride exposure inhibits testicular testosterone
      synthesis by down-regulating steroidogenic enzymes in adult rats.
AB  - Chlorocholine chloride (CCC) is widely used to regulate plant growth.
      Considerable attention has been focused on its reproductive and developmental
      toxicities. In order to investigate the effects of pubertal CCC exposure on
      testicular testosterone (T) synthesis, male SD rats were exposed to CCC by oral
      gavage at doses of 0, 75, 150 and 300 mg/kg bw/day from postnatal day 23 to 70.
      We observed that pubertal CCC exposure lowered the body weight and the mean
      Johnsen's score. The percentage of seminiferous tubules with deciduous
      spermatogenic cells was increased in the 75 and 150 mg/kg bw/day groups. In
      addition, pubertal CCC exposure reduced the testicular absolute weights in the 75
      and 300 mg/kg bw/day groups as well as the sperm motility in epididymides in the
      150 mg/kg bw/day group. A significant decrease of testicular T was observed while
      levels of hypothalamic gonadotropin-releasing-hormone (GnRH) and serum
      luteinizing hormone (LH) were increased. Protein levels of steroidogenic acute
      regulatory (StAR), cholesterol side-chain cleavage enzyme (P450scc) and 3beta
      hydroxysteroid dehydrogenase (3beta-HSD) were decreased. Taken together, these
      results indicate that pubertal CCC exposure in rats might decrease testicular T
      synthesis by suppressing the expression of steroidogenic enzymes, which partially
      lead to an impairment on spermatogenesis.

PMID- 29447957
TI  - The effects of lead exposure on the expression of HMGB1 and HO-1 in rats and PC12
      cells.
AB  - Lead (Pb) is an environmental neurotoxic metal. Chronic exposure to Pb causes
      deficits of learning and memory in children and spatial learning deficits in
      developing rats. In this study we investigated the effects of Pb exposure on the
      expression of HMGB1 and HO-1 in rats and PC12 cells. The animals were randomly
      divided to three groups: control group; low lead exposure group; high lead
      exposure group; PC12 cells were divided into 3 groups: 0 MUM (control group), 1
      MUM and 100 MUM Pb acetate. The results showed that Pb levels in blood and brain
      of Pb exposed groups were significantly higher than that of the control group (p
      < 0.05). The expression of HMGB1 and HO-1 were increased in Pb exposed groups
      than that of the control group (p < 0.05). Moreover, we found that the up
      regulation of HO-1 in Pb exposure environment inhibited the expression of HMGB1.

PMID- 29447958
TI  - Serelaxin as a novel therapeutic opposing fibrosis and contraction in lung
      diseases.
AB  - The most common therapies for asthma and other chronic lung diseases are anti
      inflammatory agents and bronchodilators. While these drugs oppose disease
      symptoms, they do not reverse established structural changes in the airways and
      their therapeutic efficacy is reduced with increasing disease severity. The
      peptide hormone, relaxin, is a Relaxin Family Peptide Receptor 1 (RXFP1) receptor
      agonist with unique combined effects in the lung that differentiates it from
      these existing therapies. Relaxin has previously been reported to have
      cardioprotective effects in acute heart failure as well anti-fibrotic actions in
      several organs. This review focuses on recent experimental evidence of the
      beneficial effects of chronic relaxin treatment in animal models of airways
      disease demonstrating inhibition of airway hyperresponsiveness and reversal of
      established fibrosis, consistent with potential therapeutic benefit. Of
      particular interest, accumulating evidence demonstrates that relaxin can also
      acutely oppose contraction by reducing the release of mast cell-derived
      bronchoconstrictors and by directly eliciting bronchodilation. When used in
      combination, chronic and acute treatment with relaxin has been shown to enhance
      responsiveness to both glucocorticoids and beta2-adrenoceptor agonists
      respectively. While the mechanisms underlying these beneficial actions remain to
      be fully elucidated, translation of these promising combined preclinical findings
      is critical in the development of relaxin as a novel alternative or adjunct
      therapeutic opposing multiple aspects of airway pathology in lung diseases.

PMID- 29447959
TI  - Effects of maturation and advanced glycation on tensile mechanics of collagen
      fibrils from rat tail and Achilles tendons.
AB  - : Connective tissues are ubiquitous throughout the body and consequently affect
      the function of many organs. In load bearing connective tissues like tendon, the
      mechanical functionality is provided almost exclusively by collagen fibrils that
      in turn are stabilized by covalent cross-links. Functionally distinct tendons
      display different cross-link patterns, which also change with maturation, but
      these differences have not been studied in detail at the fibril level. In the
      present study, a custom built nanomechanical test platform was designed and
      fabricated to measure tensile mechanics of individual fibrils from rat tendons.
      The influence of animal maturity (4 vs. 16 week old rats) and functionally
      different tendons (tail vs. Achilles tendons) were examined. Additionally the
      effect of methylglyoxal (MG) treatment in vitro to form advanced glycation end
      products (AGEs) was investigated. Age and tissue type had no significant effect
      on fibril mechanics, but MG treatment increased strength and stiffness without
      inducing brittleness and gave rise to a distinct three-phase mechanical response
      corroborating that previously reported in human patellar tendon fibrils. That age
      and tissue had little mechanical effect, tentatively suggest that variations in
      enzymatic cross-links may play a minor role after initial tissue formation.
      STATEMENT OF SIGNIFICANCE: Tendons are connective tissues that connect muscle to
      bone and carry some of the greatest mechanical loads in the body, which makes
      them common sites of injury. A tendon is essentially a biological rope formed by
      thin strands called fibrils made of the protein collagen. Tendon function relies
      on the strength of these fibrils, which in turn depends on naturally occurring
      cross-links between collagen molecules, but the mechanical influence of these
      cross-links have not been measured before. It is believed that beneficial cross
      linking occurs with maturation while additional cross-linking with aging may lead
      to brittleness, but this study provides evidence that maturation has little
      effect on mechanical function and that age-related cross-linking does not result
      in brittle collagen fibrils.

PMID- 29447960
TI  - Mechanically enhanced nested-network hydrogels as a coating material for
      biomedical devices.
AB  - : Well-organized composite formations such as hierarchical nested-network (NN)
      structure in bone tissue and reticular connective tissue present remarkable
      mechanical strength and play a crucial role in achieving physical and biological
      functions for living organisms. Inspired by these delicate microstructures in
      nature, an analogous scaffold of double network hydrogel was fabricated by
      creating a poly(2-hydroxyethyl methacrylate) (pHEMA) network in the porous
      structure of alginate hydrogels. The resulting hydrogel possessed hierarchical NN
      structure and showed significantly improved mechanical strength but still
      maintained high elasticity comparable to soft tissues due to a mutual
      strengthening effect between the two networks. The tough hydrogel is also self
      lubricated, exhibiting a surface friction coefficient comparable with
      polydimethylsiloxane (PDMS) substrates lubricated by a commercial aqueous
      lubricant (K-Y Jelly) and other low surface friction hydrogels. Additional
      properties of this hydrogel include high hydrophilicity, good biocompatibility,
      tunable cell adhesion and bacterial resistance after incorporation of silver
      nanoparticles. Firm bonding of the hydrogel on silicone substrates could be
      achieved through facile chemical modification, thus enabling the use of this
      hydrogel as a versatile coating material for biomedical applications. STATEMENT
      OF SIGNIFICANCE: In this study, we developed a tough hydrogel by crosslinking
      HEMA monomers in alginate hydrogels and forming a well-organized structure of
      hierarchical nested network (NN). Different from most reported stretchable
      alginate-based hydrogels, the NN hydrogel shows higher compressive strength but
      retains comparable softness to alginate counterparts. This work further
      demonstrated the good integration of the tough hydrogel with silicone substrates
      through chemical modification and micropillar structures. Other properties
      including surface friction, biocompatibility and bacterial resistance were
      investigated and the hydrogel shows a great promise as a versatile coating
      material for biomedical applications.

PMID- 29447961
TI  - A physiologically relevant 3D collagen-based scaffold-neuroblastoma cell system
      exhibits chemosensitivity similar to orthotopic xenograft models.
AB  - : 3D scaffold-based in vitro cell culturing is a recent technological advancement
      in cancer research bridging the gap between conventional 2D culture and in vivo
      tumours. The main challenge in treating neuroblastoma, a paediatric cancer of the
      sympathetic nervous system, is to combat tumour metastasis and resistance to
      multiple chemotherapeutic drugs. The aim of this study was to establish a
      physiologically relevant 3D neuroblastoma tissue-engineered system and explore
      its therapeutic relevance. Two neuroblastoma cell lines, chemotherapeutic
      sensitive Kelly and chemotherapeutic resistant KellyCis83 were cultured in a 3D
      in vitro model on two collagen-based scaffolds containing either
      glycosaminoglycan (Coll-GAG) or nanohydroxyapatite (Coll-nHA) and compared to 2D
      cell culture and an orthotopic murine model. Both neuroblastoma cell lines
      actively infiltrated the scaffolds and proliferated displaying >100-fold
      increased resistance to cisplatin treatment when compared to 2D cultures,
      exhibiting chemosensitivity similar to orthotopic xenograft in vivo models. This
      model demonstrated its applicability to validate miRNA-based gene delivery. The
      efficacy of liposomes bearing miRNA mimics uptake and gene knockdown was similar
      in both 2D and 3D in vitro culturing models highlighting the proof-of-principle
      for the applicability of 3D collagen-based scaffolds cell system for validation
      of miRNA function. Collectively, this data shows the successful development and
      characterisation of a physiologically relevant, scaffold-based 3D tissue
      engineered neuroblastoma cell model, strongly supporting its value in the
      evaluation of chemotherapeutics, targeted therapies and investigation of
      neuroblastoma pathogenesis. While neuroblastoma is the specific disease being
      focused upon, the platform may have multi-functionality beyond this tumour type.
      STATEMENT OF SIGNIFICANCE: Traditional 2D cell cultures do not completely capture
      the 3D architecture of cells and extracellular matrix contributing to a gap in
      our understanding of mammalian biology at the tissue level and may explain some
      of the discrepancies between in vitro and in vivo results. Here, we demonstrated
      the successful development and characterisation of a physiologically relevant,
      scaffold-based 3D tissue-engineered neuroblastoma cell model, strongly supporting
      its value in the evaluation of chemotherapeutics, targeted therapies and
      investigation of neuroblastoma pathogenesis. The ability to test drugs in this
      reproducible and controllable tissue-engineered model system will help reduce the
      attrition rate of the drug development process and lead to more effective and
      tailored therapies. Importantly, such 3D cell models help to reduce and replace
      animals for pre-clinical research addressing the principles of the 3Rs.

PMID- 29447962
TI  - Low molecular weight fucoidan attenuates liver injury via SIRT1/AMPK/PGC1alpha
      axis in db/db mice.
AB  - Non-alcoholic fatty-liver disease (NAFLD), caused by elevated hepatic lipids,
      inflammation and oxidative stress, is the most common liver disease globally. Low
      molecular weight fucoidan (LMWF), a sulfated polysaccharide extracted from brown
      seaweeds, has shown strong anti-inflammatory and antioxidant activities, which
      has not been explored in diabetes-induced NAFLD. Therefore, the present study
      sought to determine whether LMWF protects obese diabetic db/db mice against
      NAFLD. Results showed LMWF administration decreased plasma level of alanine
      aminotransferase, aspartate aminotransferase, total cholesterol, and
      triglyceride, as well as alleviated hepatic accumulation of triglyceride and
      total cholesterol in db/db mice. LMWF also ameliorated hepatic oxidative stress
      by suppressing superoxide production and lipid peroxidation, and increasing
      catalase and superoxide dismutase activity in the liver of db/db mice.
      Furthermore, LMWF down-regulated several pro-inflammatory cytokines and
      transcription factor, and up-regulated the anti-inflammatory adiponectin. These
      changes were accompanied by the activation of hepatic SIRT1/AMPK/PGC1alpha
      signaling with LMWF treatment. In addition, blocking SIRT1 or AMPK by inhibitor
      notably abolished LMWF-elicited protection against palmitic acid-induced
      oxidative stress and inflammation in hepatocytes. These results suggest LMWF
      prevents NAFLD in db/db mice by activation of SIRT1/AMPK/PGC1alpha signaling
      pathway, which prevents lipotoxicity-related oxidative stress and inflammation.
      Therefore, LMWF provides a potential supplementary treatment for obesity/diabetes
      induced NAFLD.

PMID- 29447963
TI  - In vitro and in silico investigation of anthocyanin derivatives as soluble
      epoxide hydrolase inhibitors.
AB  - Anthocyanin derivatives are well-known secondary constituents contained in
      fruits. The inhibitory activity of anthocyanin derivatives toward soluble epoxide
      hydrolase (sEH) was tested for potential applications in the treatment of
      cardiovascular diseases. Anthocyanin derivatives 1-5 showed dose-dependent
      inhibitory activity toward sEH, with IC50 values ranging from 4.3+/-0.2 to 25.3+/
      2.6MUM. Lineweaver-Burk plots showed that all anthocyanin derivatives
      preferentially interacted with allosteric sites instead of active sites as
      noncompetitive (1-3) and mixed (4 and 5) inhibitors. Furthermore, the cavity
      located next to the active site may interact with anthocyanin derivatives (1-5)
      by molecular docking. Among the tested derivatives, (4) bonded with key amino
      acids at two loops around the binding site for 10ns. Finally, anthocyanin
      derivatives (1-5) are potential inhibitors of sEH, and anthocyanin-rich fruits
      may be useful for the targeted treatment of cardiovascular diseases via sEH
      inhibition.

PMID- 29447964
TI  - Botulinum toxin type A relieves sternocleidomastoid muscle fibrosis in congenital
      muscular torticollis.
AB  - Congenital muscular torticollis (CMT) is a neck deformity that involves
      shortening of sternocleidomastoid muscle (SCM) characterized by muscle atrophy
      and interstitial fibrosis. To investigate wheatear Botulinum toxin type A (BTA)
      has anti-fibrotic effects in CMT, we established acquired muscular torticollis
      that mimetics CMT in rabbit by intra-SCM injection of anhydrous alcohol. The
      treatment groups received BTA (2.5units or 5units) injection into the fibrotic
      SCM. The shortening and thickening of SCM were recorded by B-mode ultrasound.
      Changes in Col1A1, Fn, alpha-SMA expression were determined by
      immunohistochemistry. In vitro studies, TGF-beta induced NIH3T3 fibroblasts were
      used to evaluate anti-fibrosis effect of BTA. Expression of the myofibroblast
      marker alpha-SMA and fibrosis markers Col1A1 and Fn were detected by Western
      blotting and quantitative RT-PCR. Our results showed that BTA injection
      attenuated shortening and thickening of fibrotic SCM. Elevated expression of
      Col1A1, Fn, alpha-SMA were confirmed in this fibrotic muscle model but reversed
      after BTA injection. Similar results observed in TGF-beta induced NIH3T3
      fibroblasts in both mRNA and protein levels. In conclusion, our results suggested
      that BTA could be a promising agent against SCM fibrosis in CMT through
      regulating fibroblast and inhibiting myofibroblast differentiation.

PMID- 29447965
TI  - Simple fabrication of Chitosan/Graphene nanoplates composite spheres for
      efficient adsorption of acid dyes from aqueous solution.
AB  - A facile method for the fabrication of crosslinked chitosan/graphene nanoplates
      composite sphere (CS/GNPs) was presented. The obtained samples were characterized
      by transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray
      photoelectron spectroscopic (XPS) and thermogravimetric analysis (TGA). The
      adsorption activities of CS/GNPs for methyl orange (MO) and acid red 1 (AR1) were
      evaluated such as the effect of pH and GNPs content, as well as adsorption
      kinetics and isotherms. In view of practical, the reusability of CS/GNPs was also
      tested. The resulting adsorption capacity for MO is 230.91mgg-1 and 132.94mgg-1
      for AR1, respectively. After saturated adsorption, CS/GNPs can be efficiently
      regenerated and reused with little uptake loss. Therefore, CS/GNPs is the
      apromising adsorbent with non-toxic, efficient, low-cost and easy to prepare for
      the dye removal.

PMID- 29447966
TI  - Molecular insights on the interaction and preventive potential of
      epigallocatechin-3-gallate in Celiac Disease.
AB  - Celiac Disease (CD) is now recognized as a worldwide epidemic. Although a gluten
      free diet usually induces clinical improvements within days or weeks, adhering to
      this routine is still troublesome. Therefore, new solutions are needed for
      quality-of-life improvement of CD patients. The present work intends to bring
      molecular and thermodynamic insights on the ability of green tea epigalhocatechin
      3-gallate (EGCG) to interact and modulate the bioavailability of a major CD
      immunodominant peptide (32-mer). Characterization of peptide binding was assessed
      by means of both 1D and 2D 1H NMR experiments, ITC and Molecular Dynamics
      simulations. Accordingly, EGCG not only exhibits a high reactivity towards the 32
      mer peptide as its binding appears to be entropy-driven and involves two
      sequential binding events, each with different binding strengths. Structural
      rearrangements were also detected during the interaction, contributing to a
      greater stability of the formed complexes. In vitro transepithelial transport
      assays using a Caco-2 cell line model were also performed and highlighted the
      ability of EGCG to significantly reduce the concentration of free peptide in the
      basolateral compartment. Overall, this study provides important evidences
      regarding the structural features and molecular mechanisms by which EGCG could
      interact and potentially modulate the function of some bioactive CD peptides.

PMID- 29447967
TI  - Fabrication and characterization of chitosan conjugated eurycomanone
      nanoparticles: In vivo evaluation of the biodistribution and toxicity in fish.
AB  - Chitosan nanoparticles (CNPs) have been proven considerable delivery agents due
      to their remarkable physicochemical properties. Present study reports the
      fabrication of CNPs by ionic gelation process and their characterization by
      different approaches. The constructed nanoparticles were successfully conjugated
      with eurycomanone with significant entrapment efficiency. Particle size of
      chitosan and chitosan conjugated eurycomanone nanoparticles were 126.2nm and
      130nm respectively. Scanning electron microscopy showed that the particles were
      spherical in shape and well dispersed. Cross-linking between CNPs and
      eurycomanone (CENPs) were confirmed by Fourier-transform infrared (FTIR)
      spectroscopy. Fluorescent nanoparticles were prepared by using Rhodamine-6G dye,
      characterised by SEM and confirmed for conjugation by FTIR. Biodistribution of
      CENPs showed the presence of fluorescent nanoparticles in liver, kidney, testes
      and brain of C. magur. The toxicity of CENPs was evaluated by comparing the
      histological sections of catfish testes collected from treated and control group.
      No signs of toxicity were seen in testes after the delivery of CENPs. Molecular
      docking study revealed high spontaneous binding ability of chitosan with
      eurycomanone and aromatase enzyme. The study reports that CNPs can act as a
      stabilizing agent for eurycomanone formulation and could be a promising approach
      to increase the reproductive performance of the fishes.

PMID- 29447968
TI  - Impact of acidic, water and alkaline extraction on structural features,
      antioxidant activities of Laminaria japonica polysaccharides.
AB  - This study comparatively evaluated the effects of different extraction methods on
      yield, structural features and antioxidant activities of Laminaria japonica (L.
      japonica) polysaccharides. Results showed that acid, water and alkaline extracted
      L. japonica polysaccharides (LJP-CA, LJP-W and LJP-A, respectively) differed
      significantly. Among three polysaccharides, LJP-W showed the highest viscosity
      with high uronic acid content and average molecular weight, whereas LJP-CA showed
      the lowest viscosity with low uronic acid and high sulfate content with moderate
      average molecular weight. LJP-CA was mainly composed of fucose, mannose and
      galactose, but the proportion of glucose was greatly increased in LJP-W and LJP
      A. LJP-W had an even and smooth sheet-like appearance, while LJP-CA and LJP-A
      exhibited irregular and rough fragments or particles with stronger antioxidant
      activities. These results suggest that acid and alkali would propose an improved
      process for polysaccharide preparation from L. japonica and to exploit its
      potential application as a functional ingredient in food application.

PMID- 29447969
TI  - Novel piperonal 1,3,4-thiadiazolium-2-phenylamines mesoionic derivatives:
      Synthesis, tyrosinase inhibition evaluation and HSA binding study.
AB  - A novel series of piperonal mesoionic derivatives (PMI 1-6) was synthesized.
      Tyrosinase inhibition in the presence of PMI-1, -2, -3, -4, -5 and -6 as well as
      human serum albumin (HSA) binding studies with PMI-5 and PMI-6 were done by
      spectroscopic and theoretical methods. The mesoionic compound PMI-5 is the most
      promising tyrosinase inhibitor with a noncompetitive inhibitory mechanism and an
      IC50=124MUmolL-1. In accordance with the kinetic profile, molecular docking
      results show that PMI-5 is able to interact favorably with the tyrosinase active
      site containing the substrate molecule, L-DOPA, interacting with Val-247, Phe-263
      and Val-282 residues. The spectroscopic results for the interaction HSA:PMI-5 and
      HSA:PMI-6 indicated that these mesoionic compounds can associate with HSA in the
      ground state and energy transfer can occur with high probability. The binding was
      moderate, spontaneous and can perturb significantly the secondary structure of
      the albumin. The molecular docking results suggest that PMI-5 and PMI-6 are able
      to be accommodated inside the Sudlow's site I in HSA, interacting with
      hydrophobic and hydrophilic amino acid residues.

PMID- 29447970
TI  - Development of a new paper based nano-biosensor using the co-catalytic effect of
      tyrosinase from banana peel tissue (Musa Cavendish) and functionalized silica
      nanoparticles for voltammetric determination of l-tyrosine.
AB  - In this paper, a new and facile method for the electrochemical determination of l
      tyrosine was designed. First, 3-mercaptopropyl trimethoxysilane-functionalized
      silica nanoparticles were added to a paper disc. Then, the banana peel tissue and
      the mediator potassium hexacyanoferrate were dropped onto the paper,
      respectively. The modified paper disc was placed on the top of the graphite
      screen printed electrode and electrochemical characterization of this biosensor
      was studied by cyclic voltammetry and electrochemical impedance spectroscopy
      methods. The effective parameters like pH, banana peel tissue percentage, and the
      amount of mediator loading were optimized. l-tyrosine measurements were done by
      differential pulse voltammetry with a little sample (3 MUL) for analysis. The
      biosensor showed a linear response for l-tyrosine in the wide concentration range
      of 0.05-600 MUM and a low detection limit about 0.02 MUM because of the co
      catalytic effect of enzyme and nanoparticles. The stability of the biosensor and
      its selectivity were evaluated. This biosensor was applied for the voltammetric
      determination of l-tyrosine in the blood plasma sample. The results of the
      practical application study were comparable with the standard method (HPLC). In
      conclusion, a simple, inexpensive, rapid, sensitive and selective technique was
      successfully applied to the l-tyrosine analysis of the little samples.

PMID- 29447971
TI  - Horseradish peroxidase immobilization by copolymerization into cross-linked
      polyacrylamide gel and its dye degradation and detoxification potential.
AB  - Owing to the ever-increasing environmental and health impacts associated with the
      discharge of dye-based effluents, effective remediation of industrial waste have
      become a top priority for the industrialists and environmental fraternity, around
      the world. Plant-based peroxidases represent a suitable bio-remediating agent for
      the effective treatment of original dyes or dye-based colored wastewater
      effluents. In the present study, horseradish peroxidase was immobilized by
      copolymerization into cross-linked polyacrylamide gel and investigated its
      potential for the degradation and detoxification of an azo dye, methyl orange. In
      the presence of N, N'-methylenebisacrylamide as a cross-linker, polyacrylamide
      gel at 10% concentration furnished >80% of immobilization yield. The surface
      morphology of the control (free enzyme) and immobilized enzyme, i.e., horseradish
      peroxidase cross-linked polyacrylamide gel was characterized using scanning
      electron microscopy. The high yielded horseradish peroxidase cross-linked
      polyacrylamide gel concentration, i.e., 10% was used to develop a packed bed
      reactor and exploited for dye degradation and detoxification purposes. A
      noteworthy level (>90%) of dye degradation was recorded after polyacrylamide gel
      cross-linked horseradish peroxidase-catalyzed reaction in a packed bed
      bioreactor. The biodegradation was further assessed by Fourier-transform infrared
      spectral analysis. The acute toxicity assays demonstrated that enzyme-based bio
      degradation might be used effectively for large-scale environmental remediation
      of dyes and dyes containing wastewater effluents.

PMID- 29447972
TI  - Novel asymmetric chitosan/PVP/nanocellulose wound dressing: In vitro and in vivo
      evaluation.
AB  - The present study was to develop a novel chitosan based symmetric and asymmetric
      bionanocomposite for potential wound dressing application. Chitosan (C)/Poly
      (vinyl pyrrolidone) (P)/nanocellulose (NC) membrane were fabricated by salt
      leaching method with the addition of 3% and 5% wt of nanocellulose. To obtain
      asymmetric material one side of the membrane was coated by stearic acid (S) which
      could form hydrophobic surface and another side acts as a hydrophilic surface.
      Nanocellulose of size 2-10nm was synthesized and characterized by TEM analysis.
      SEM showed the hydrophilic surface of asymmetric bionanocomposite consists of
      porous structure and hydrophobic surface is smooth and homogeneous. The results
      revealed that the Chitosan/PVP/Nanocellulose 3%-Stearic acid (CPNC3%-S) had a
      moderate swelling ratio, porosity, barrier and mechanical properties.
      Incorporation of nanocellulose into chitosan/PVP matrix could enhance the
      antibacterial activity. The hydrophobic surface of the CPNC3%-S bionanocomposite
      shows water repellent and antiadhesion properties towards E. coli bacteria and
      also the hydrophilic surface exhibit excellent antibacterial property and
      cytotoxicity towards bacterial pathogens. In vivo wound healing test shows better
      re-epithelialization and wound contraction compared with control and Chitosan/PVP
      stearic acid (CP-S) bionanocomposite. Asymmetric bionanocomposite
      Chitosan/PVP/Nanocellulose coated with 3%-Stearic acid (CPNC3%-S) exhibited very
      good invitro cytocompatibility and enabled a faster wound healing than symmetric
      dressing, hence showing great potential to be applied as wound dressings.

PMID- 29447973
TI  - Extraction, purification and antioxidation of a polysaccharide from Fritillaria
      unibracteata var. wabuensis.
AB  - Rich polysaccharides were directly observed in the bulbs of Fritillaria
      unibracteata var. wabuensis (FUW) using the periodic acid-Schiff (PAS) method and
      microexamination. An acidic water-soluble heteropolysaccharide (FWPS1-1) was
      isolated from FUW through ethanol precipitation, decoloration, deproteinization,
      dialysis and separation using a DE-52 anion-exchange column and a Sepharose G-150
      gel filtration column. FWPS1-1 (average molecular weight: ~7.44 kDa) has many
      branches and long side chains; holds the triple-helix conformation; was composed
      of mannose (Man), galacturonic acid (GalA), galactose (Gal), xylose (Xyl) and
      arabinose (Ara) with a molar ratio of 2.62:5.59:10.00:0.76:9.38; and features
      side chains that may be composed of Ara, Man, Gal and GalA, while the backbone
      may be composed of Xyl, Ara and Gal. In addition, the backbone of FWPS1-1 mainly
      consists of alpha-type glycosidic bonds. Bioactivity tests in vitro showed that
      the polysaccharide exhibited weak 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      scavenging activity and low ferric reducing antioxidant power (FRAP) but high 2,2
      azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)l (ABTS) radical scavenging
      activity, good Fe(II)-chelating ability and remarkable DNA damage protective
      activity. FWPS1-1 was the first heteropolysaccharide purified from FUW and showed
      good antioxidant activity and DNA protective effect. The results confirmed that
      macromolecule is also bioactive ingredient that requires attention like the small
      molecule active compounds in FUW.

PMID- 29447974
TI  - The U.K. approach to putting patient safety first when receiving non-surgical
      cosmetic therapies: The cosmetic practice standards authority.

PMID- 29447975
TI  - Profiling of novel microRNAs elicited by EV71 and CA16 infection in human
      bronchial epithelial cells using high-throughput sequencing.
AB  - Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are two major etiologic
      agents associated with hand, foot, and mouth disease (HFMD) worldwide. Despite
      that they both belong to the Enterovirus genus of the Picornaviridae family,
      there are many differences in the infection process of these viruses. However,
      the underlying mechanisms have not been elucidated. Multiple studies indicated
      that microRNAs (miRNAs) can play critical roles in the host-pathogen interaction.
      Our previous study reported that EV71 and CA16 infection leads to differential
      expression of miRNAs in human bronchial epithelial (16HBE) cells. Herein, we
      aimed to further explore the expression profile and possible roles of other
      differentially expressed miRNAs in 16HBE cells following EV71 and CA16 infections
      using high-throughput sequencing. We describe 44 novel differentially expressed
      miRNAs in all samples. Among these miRNAs, 7 novel differentially expressed
      miRNAs show an opposite expression trend during the progression of EV71 and CA16
      infections. Subsequently, bioinformatics analyses, including Gene Oncology (GO)
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were used to
      identify the biological processes, molecular functions, cellular components, and
      pathways involved. The top 10 significant GO and Pathway annotations indicated
      that 849 target genes are involved in cell development, such as nervous system
      development, multicellular organism development, and developmental biology.
      Finally, the genes identified in both the GO and Pathway analysis were used to
      construct a co-expression network to further identify the potential function of
      these co-expressed genes. Thus, our data may be beneficial in guiding further
      studies on the molecular mechanism of developmental regulation in HFMD
      pathogenesis caused by EV71 and CA16. In addition, it provided new candidate
      biomarkers or therapeutic targets for HFMD.

PMID- 29447976
TI  - Identification of a novel host protein SINAL10 interacting with GP64 and its role
      in Bombyx mori nucleopolyhedrovirus infection.
AB  - Bombyx mori nucleopolyhedrovirus (BmNPV) is the most important pathogen of Bombyx
      mori, silkworm and causes severe losses in the silk industry. During the virus
      infectious cycle, budded virus (BVs) and occlusion-derived virus (ODVs)
      particles, which have identical genetic content but different phenotypes, are
      produced. The envelope glycoprotein GP64, specific in BVs, is involved in host
      cell receptor binding and is sufficient to mediate membrane fusion during the
      viral entry. However, the host cell factors, interacting with GP64 to mediate BVs
      infection, are still unknown. In this study, a cDNA library of Bombyx mori cells
      (BmN) was constructed and yeast two-hybrid screening was used to identify the
      host cell factors interacting with GP64. One of the eight candidate proteins
      encoded the E3 ubiquitin-protein ligase SINA-like 10 (SINAL10), was further
      confirmed through coimmunoprecipitation assays as novel GP64 binding protein.
      Moreover, overexpression of SINAL10 significantly enhances viral reproduction,
      and conversely, silencing its expression by small interfering RNAs showed
      significant inhibitory effects. Collectively, we demonstrated that SINAL10 is a
      novel GP64-binding protein that stimulates BmNPV proliferation.

PMID- 29447977
TI  - Serratene-type triterpenoids from Palhinhaea cernua.
AB  - Phytochemical investigation of the 95% ethanol extract of the whole plant of
      Palhinhaea cernua afforded five new serratene-type triterpenoids (1-5) together
      with four known analogues (6-9). The structures of the new compounds were
      elucidated by extensive spectroscopic analysis and X-ray crystallographic data.
      Compounds 1-3 triggered apoptosis of Hela-/- cell with EC50 values of 3.49 +/-
      0.05, 0.28 +/- 0.13 and 7.98 +/- 0.03 MUM, respectively.

PMID- 29447978
TI  - The influence of procyanidins isolated from small-leaved lime flowers (Tilia
      cordata Mill.) on human neutrophils.
AB  - Linden flower is a wildly used plant material among patients in the treatment of
      common cold symptoms and mucosa inflammations. However, the structure and
      bioactivity of flavan-3-ol derivatives present in infusions from flowers of Tilia
      cordata have not been studied so far. The aim of current study was to isolate and
      identify main procyanidins present in the flowers of small-leaved lime and to
      evaluate their influence on the inflammatory response of human neutrophils ex
      vivo. The chemical structure of isolated compounds was established by 1D and 2D
      NMR experiments. The bioactivity of obtained compounds was tested in human
      neutrophils model. Cytotoxicity and influence of compounds on apoptosis was
      established by flow cytometry. The levels of produced cytokines were established
      by ELISA after stimulation with lipopolysaccharide (LPS). The inhibition of the
      production of reactive oxygen species was checked by luminol-dependent
      chemiluminescence method after N-formylmethionyl-leucyl-phenylalanine (f-MLP)
      induction. The phytochemical work resulted in the isolation of 10 compounds.
      Compounds were identified as oligomeric procyanidins and their precursor
      epicatechin. The potential anti-inflammatory activity of compounds was evaluated
      in the concentration range 5-20 MUM. All compounds were able to decrease the
      production of ROS from f-MLP-stimulated neutrophils. Most of compounds were able
      to inhibit the LPS-induced release of IL-8. Some trimeric and tetrameric
      derivatives were also able to decrease the production of MIP-1beta. Obtained
      results partially support the traditional usage of infusion from lime flowers in
      the treatment of symptoms of inflammation and irritation of mucosa in common
      cold, pharyngitis and tonsillitis.

PMID- 29447979
TI  - Jatrophanes as promising multidrug resistance modulators: Advances of structure
      activity relationships.
AB  - The phytochemical study of Euphorbia helioscopia afforded euphornin (1) in a
      large amount. Alkaline hydrolysis of 1 using potassium carbonate yielded the main
      product monodeacetyleuphornin (2), whose structural modification at 14-OH gave
      rise to 21 acylated derivatives euphornoate A-U (3-23). Thus, a mini compound
      library of jatrophanes was established to screen for MDR modulators. Biological
      studies clearly demonstrated the effect of C-14 pattern modification in MDR
      reversal activity and several compounds with RF values over 300 fold at 20 MUM
      (6, 16, 20, 22, 23) were thought to be promising MDR modulators. The SARs are
      discussed, which reveal that introduction of an alkyl acyl group bearing 4
      carbons at C-14 or an aryl acyl group with electron donating groups is favorable
      for the activity.

PMID- 29447980
TI  - Megastigmane glycosides from Urena lobata.
AB  - Five new megastigmane glycosides, urenalobasides A-E (1-5), together with 11
      known ones (6-16) were isolated from Urena lobata. Their structures were
      determined by extensive spectroscopic and spectrometric data (1D and 2D NMR, IR,
      and HRESIMS) and calculated electronic circular dichroism method. Compounds 1 and
      2 are two unusual megastigmanes structurally containing a 6/5 fused ring system.
      Compound 3 exhibits inhibition of nitric oxide production in lipopolysaccharide
      (LPS)-stimulated RAW264.7 macrophage cells with IC50 value of 53.7 +/- 1.0 MUM
      (positive control, dexamethasone, IC50 = 16.6 +/- 0.8 MUM).

PMID- 29447981
TI  - Evaluation of in vitro/in vivo anti-diabetic effects and identification of
      compounds from Physalis alkekengi.
AB  - The aims of the present study were to assess the anti-diabetic effects of
      Physalis alkekengi L. (PA) in 3T3-L1 pre-adipocyte cells and HepG2-GFP-CYP2E1
      (E47) cells and in a pre-diabetic rat model, as well as to identify the active
      chemical constituents. The in vitro results showed that PA has a strong anti
      diabetic capacity to relieve oxidative stress and inhibit alpha-glucosidase
      activity. Mechanistic analysis also showed that ethyl acetate extracts of aerial
      parts and fruit of PA (PAG-EA and PAF-EA) enhanced glucose transporter 4
      expression and function as well as enhanced insulin sensitivity by inhibiting the
      expression of cytochrome P450-2E1 (CYP2E1) mRNA and protein. In vivo, PAG-EA and
      PAF-EA significantly decreased the levels of fasting blood glucose and fasting
      insulin, as well as total cholesterol and triglyceride, in the pre-diabetic rats.
      The results from insulin sensitivity index and homeostasis model assessment
      insulin resistance index along with an oral glucose tolerance test also showed
      that PAG-EA and PAF-EA could significantly enhance the insulin sensitivity, which
      confirmed the in vitro findings. Moreover, HPLC-ESI-QTOF-MS analysis identified
      flavonoids, physalins and phenolic acids as the main plant constituents. Our
      findings support the ethnopharmacological use of PA fruit, along with its aerial
      parts, as a strong anti-diabetic agent. The EA fraction, especially the
      constituent polyphenols and flavonoids, may have a good potential to treat
      diabetes.

PMID- 29447982
TI  - Spongian diterpenes from Chinese marine sponge Spongia officinalis.
AB  - 3-Nor-spongiolide A (1), belonging to the extremely rare 3-nor-spongian carbon
      skeleton, and spongiolides A (2) and B (3), having gamma-butenolide instead of
      furan ring as usual for ring D, together with six related known metabolites were
      isolated from South China Sea sponge Spongia officinalis as its metabolic
      components. Their structures were elucidated on the basis of extensive
      spectroscopic analysis. The absolute configurations of three new compounds 1-3
      were determined by ECD calculations.

PMID- 29447983
TI  - Three new abietane-type diterpenoids from the leaves of Indonesian Plectranthus
      scutellarioides.
AB  - Three new diterpenoids, spiroscutelones A-C (1-3), along with known diterpene 4,
      were isolated from the leaves of Plectranthus scutellarioides. Their structures
      were established based on extensive spectroscopic analyses, including MS and NMR
      spectroscopy. Spiroscutelone A (1) represents the first example of an abietane
      type terpenoid skeleton with a cyclobutane moiety linking the B and C rings. Of
      compounds 1-4, spiroscutelone B (2) exhibited the most potent cytotoxicities
      against the three tested human cancer lines [breast (MCF-7), pancreatic (PSN-1),
      and cervical (HeLa)] with IC50 values ranging from 17.9 MUM to 29.8 MUM and low
      cytotoxicity against a lung fibroblast (WI-38) normal cell line.

PMID- 29447984
TI  - Salicin-7-sulfate: A new salicinoid from willow and implications for herbal
      medicine.
AB  - Willow (Salix sp.) is a historically well-known herbal medicine that provided the
      lead compound (salicin) for the discovery of aspirin, one of the most successful
      plant derived drugs in human medicine. During a metabolomics screen of 86 Salix
      species contained in the UK National Willow Collection, we have discovered,
      isolated and fully characterised a new natural salicinoid - salicin-7-sulfate.
      This molecule may have important human pharmacological actions that need to be
      considered in determining the efficacy and safety of willow herbal medicines.

PMID- 29447986
TI  - WITHDRAWN: Research progress of cGAS-STING pathway in infectious diseases.
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- 29447985
TI  - Selected terpenes from leaves of Ocimum basilicum L. induce hemoglobin
      accumulation in human K562 cells.
AB  - Re-expression of fetal hemoglobin (HbF) was proposed as a possible therapeutic
      strategy for beta-haemoglobinopathies. Although several inducers of HbF were
      tested in clinical trials, only hydroxyurea (HU) received FDA approval. Despite
      it produced adequate HbF levels only in half of HU-treated SCD patients, and was
      ineffective at all in beta-thalassemia patients, beneficial effects of this
      approach suggested to continue in this direction identifying further molecules
      capable of inducing HbF. We tested the potential of essential oil isolated from
      Ocimum basilicum L. leaves (ObEO) in inducing hemoglobin biosynthesis. Initially,
      dose-dependent effect and kinetics of hemoglobin accumulation in K562 cells after
      treatment with ObEO were evaluated. ObEO induced dose-dependent hemoglobin
      accumulation superior to hydroxyurea and rapamycin and a strongest gamma-globin
      mRNA expression. Terpenes composition of ObEO was studied by GC-MS. Three main
      constituents, linalool, eugenol and eucalyptol, represented about 75% of total. A
      blend of these three terpenes fully replicated the ObEO's biological effect, thus
      indicating that one of them or all together could be the active ingredients. When
      terpenes were tested individually, eugenol was the only one inducing stable
      hemoglobin accumulation, while eucalyptol and linalool produced only a small
      transient response. However, eugenol potential was strongly enhanced in the
      presence of eucalyptol and linalool, suggesting a synergistic effect on
      hemoglobin accumulation. By these results, the discovery of a new inducer and the
      interesting activity of a blend of major terpenes from ObOE on Hb accumulation
      could have positive fallouts on beta-thalassemia and sickle cells anemia.

PMID- 29447987
TI  - ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus
      Document on the safety of targeted and biological therapies: an infectious
      diseases perspective (Soluble immune effector molecules [II]: agents targeting
      interleukins, immunoglobulins and complement factors).
AB  - BACKGROUND: The present review is part of the ESCMID Study Group for Infections
      in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and
      biological therapies. AIMS: To review, from an Infectious Diseases perspective,
      the safety profile of agents targeting interleukins, immunoglobulins and
      complement factors and to suggest preventive recommendations. SOURCES: Computer
      based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic
      family. CONTENT: Patients receiving interleukin-1 (IL-1) -targeted (anakinra,
      canakinumab or rilonacept) or IL-5-targeted (mepolizumab) agents have a moderate
      risk of infection and no specific prevention strategies are recommended. The use
      of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated
      with a risk increase similar to that observed with anti-tumour necrosis factor
      alpha agents. IL-12/23-targeted agents (ustekinumab) do not seem to pose a
      meaningful risk of infection, although screening for latent tuberculosis
      infection may be considered and antiviral prophylaxis should be given to
      hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents
      (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to
      moderate mucocutaneous candidiasis. Pre-treatment screening for Strongyloides
      stercoralis and other geohelminths should be considered in patients who come from
      areas where these are endemic who are receiving IgE-targeted agents (omalizumab).
      C5-targeted agents (eculizumab) are associated with a markedly increased risk of
      infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal
      vaccination and chemoprophylaxis must be administered 2-4 weeks before initiating
      eculizumab. Patients with high-risk behaviours and their partners should also be
      screened for gonococcal infection. IMPLICATIONS: Preventive strategies are
      particularly encouraged to minimize the occurrence of neisserial infection
      associated with eculizumab.

PMID- 29447989
TI  - Aetiology of lower respiratory tract infection in adults in primary care: a
      prospective study in 11 European countries.
AB  - OBJECTIVES: To describe the role of bacteria (including bacterial resistance),
      viruses (including those recently described) and mixed bacterial-viral infections
      in adults presenting to primary care with lower respiratory tract infection
      (LRTI). METHODS: In all, 3104 adults with LRTI were enrolled, of whom 141 (4.5%)
      had community-acquired pneumonia (CAP), and 2985 matched controls in a
      prospective study in 16 primary care networks in Europe, and followed patients up
      at 28-35 days. We detected Streptococcus pneumoniae and Haemophilus influenzae
      and assessed susceptibility, atypical bacteria and viruses. RESULTS: A potential
      pathogen was detected in 1844 (59%) (in 350 (11%) bacterial pathogens only, in
      1190 (38%) viral pathogens only, and in 304 (10%) both bacterial and viral
      pathogens). The most common bacterial pathogens isolated were S. pneumoniae (5.5%
      overall, 9.2% in CAP patients) and H. influenzae (5.4% overall, 14.2% in CAP
      patients). Less than 1% of S. pneumoniae were highly resistant to penicillin and
      12.6% of H. influenzae were beta-lactamase positive. The most common viral
      pathogens detected were human rhinovirus (20.1%), influenza viruses (9.9%), and
      human coronavirus (7.4%). Influenza virus, human parainfluenza viruses and human
      respiratory syncytial virus as well as human rhinovirus, human coronavirus and
      human metapneumovirus were detected significantly more frequently in LRTI
      patients than in controls. CONCLUSIONS: A bacterial pathogen is identified in
      approximately one in five adult patients with LRTI in primary care, and a viral
      pathogen in just under half, with mixed infections in one in ten. Penicillin
      resistant pneumococci and beta-lactamase-producing H. influenzae are uncommon.
      These new findings support a restrictive approach to antibiotic prescribing for
      LRTI and the use of first-line, narrow-spectrum agents in primary care.

PMID- 29447988
TI  - ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus
      Document on the safety of targeted and biological therapies: an infectious
      diseases perspective (Agents targeting lymphoid cells surface antigens [I]: CD19,
      CD20 and CD52).
AB  - BACKGROUND: The present review is part of the ESCMID Study Group for Infections
      in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and
      biological therapies. AIMS: To review, from an Infectious Diseases perspective,
      the safety profile of agents targeting CD19, CD20 and CD52 and to suggest
      preventive recommendations. SOURCES: Computer-based MEDLINE searches with MeSH
      terms pertaining to each agent or therapeutic family. CONTENT: Although CD19
      targeted agents (blinatumomab or inebilizumab) are not associated with an
      increased risk of infection, they may cause IgG hypogammaglobulinaemia and
      neutropenia. The requirement for prolonged intravenous infusion of blinatumomab
      may increase the risk of catheter-associated bloodstream infections. Infection
      remains the most common non-haematological adverse effect of anti-CD20 monoclonal
      antibodies, including severe respiratory tract infection, hepatitis B virus (HBV)
      reactivation and varicella-zoster virus infection. Screening for chronic or
      resolved HBV infection is recommended for patients receiving anti-CD20 monoclonal
      antibodies. Antiviral prophylaxis should be offered for 12-18 months to hepatitis
      B surface antigen (HBsAg)-positive and HBsAg-negative/anti-hepatitis B core
      antibody (HBc)-positive patients. Anti-Pneumocystis prophylaxis should be
      considered in patients receiving concomitant chemotherapy, particularly steroids.
      Alemtuzumab (anti-CD52) increases the risk of infections, in particular among
      leukaemia and solid organ transplant patients. These populations benefit from
      anti-Pneumocystis prophylaxis, prevention strategies for cytomegalovirus
      infection, and screening for HBV, hepatitis C virus and tuberculosis. Antiviral
      prophylaxis for at least 6-12 months should be provided for HBsAg-positive
      patients. IMPLICATIONS: As there are limited clinical data for many of the
      reviewed agents, special attention must be given to promptly detect and report
      emerging infectious complications.

PMID- 29447990
TI  - Koro in panic disorder: Beyond a culture bound phenomena.

PMID- 29447991
TI  - Severe extrapyramidal syndrome presenting as catatonia: A rare case report.

PMID- 29447992
TI  - Sertraline induced cervical dystonia in a patient of Obsessive Compulsive
      Disorder.

PMID- 29447993
TI  - Restricted and repetitive behaviours in autism spectrum disorder through a
      clinical lens!

PMID- 29447994
TI  - Who eats with family and how often? Household members and work styles influence
      frequency of family meals in urban Japan.
AB  - Family commensality, or meals eaten together with family members, is a key
      practice to understand the socio-cultural organization of eating and family
      lives. Yet empirical evidence is limited outside of western societies, which have
      different household structures, work styles, and socio-cultural constructions of
      the practice. This study examined frequencies of family commensality based on 242
      surveys of Japanese adults aged between 20 and 85 in two metropolitan areas.
      Results showed that family commensality is less frequent not only among those
      living alone, but also among those living with only non-partners including adult
      children, parents, and non-family members, than among those living with partners.
      Full-time employment was associated with late dinner times on weekdays. Later
      weekday dinner times were strongly associated with reduced frequency of dinners
      together. Late dinners have become commonplace among full-time workers in postwar
      Japan, and the peak dinner time in Japan occurs later than in other developed
      countries. Thus, work and lifestyle constraints impacting schedules appear to
      influence the frequency of family commensality. Our results suggest that
      frequencies of family commensality are influenced by co-residents and work styles
      of participants rather than household sizes. The idea that reduction of household
      size drives reduction of family commensality may be biased by previous studies
      conducted in western countries where most people reside in either single or
      nuclear households. Our study highlights complex determinants of family
      commensality, beyond presence of other household members, and demonstrates a need
      for rigorous investigation of family commensality across cultures.

PMID- 29447995
TI  - How effective are messages and their characteristics in changing behavioural
      intentions to substitute plant-based foods for red meat? The mediating role of
      prior beliefs.
AB  - By means of a population-based survey experiment, we analysed the effectiveness
      of two message characteristics - message framing and the refutation of
      misinformation - in persuading respondents to reduce their consumption of red
      meat and increase that of plant-based alternatives. We also tested whether the
      effects of those two message characteristics were moderated by prior beliefs
      about the health and climate impacts of red meat consumption. The data were
      collected with an online survey of the adult population living in Finland (N =
      1279). We found that messages had a small but desired effect on intentions when
      the effect of prior beliefs was taken into account, but that that effect was
      strongly moderated by prior beliefs. In particular, messages changed behavioural
      intentions among the "meat-sceptics" (i.e., those believing relatively strongly
      in the negative health and climate effects of meat consumption) but not among the
      "meat believers" (defined symmetrically). The combination of frames and
      refutation of misinformation were not found to be more effective strategies than
      the provision of information through single-framed, one-sided messages. We found
      limited evidence that the way a message was formulated determined its
      effectiveness in changing behaviours.

PMID- 29447996
TI  - Sleep, food cravings and taste.
AB  - OBJECTIVE: Taste is influenced by factors from our environment, psychology, and
      from our own physiological state. The objective of the study was to determine
      whether sleep influences our sense of taste or our cravings for food. METHOD: 57
      healthy panelists, predominantly of college age, submitted to sleep tracking, and
      subsequently underwent a series of sensory tests, using basic prototypic
      tastants, as well as real foods. Panelists were also evaluated to quantify food
      cravings, using both the Leeds Food Preference Questionnaire, and the Control of
      Eating Questionnaire. RESULTS: Umami (p = 0.025, F = 5.301) and sour (p = 0.037,
      F = 4.591) taste were intensified in those rating sleepiness higher, while this
      group also reported higher implicit wanting for high fat sweet foods (p = 0.011,
      Wald chi-sq = 14.937). Craving for sweet or savory also associated with a number
      of measures of taste response to real foods. CONCLUSIONS: Results imply that a
      lack of sleep may induce cravings for unhealthy foods, and that foods high in
      umami or sour taste may be experienced differently due to alterations in taste
      function. Results imply that feeding behavior may be influenced by a lack of
      sleep, acting at least partially through our sense of taste.

PMID- 29447997
TI  - Multisensory flavor perception: The relationship between congruency,
      pleasantness, and odor referral to the mouth.
AB  - Our hedonic response to a food is determined by its flavor, an inherently
      multisensory experience that extends beyond the mere addition of its odor and
      taste. While congruency is known to be important for multisensory processes in
      general, little is known about its specific role in flavor processing. The aim of
      the present study was to delineate the effects of odor-taste congruency on two
      central aspects of flavor: odor referral (or mislocalization) to the mouth, and
      pleasantness. We further aimed to test whether an eventual effect on pleasantness
      was mediated by odor referral. Aqueous solutions containing odors and tastes were
      prepared to create food-like stimuli with varying degrees of congruency, ranging
      from maximally incongruent to maximally congruent in nine steps. Thirty
      participants reported where they perceived the odors, and how much they liked the
      solutions. Congruency had a positive linear effect both on odor referral to the
      oral cavity and on pleasantness. However, the effect of congruency on
      pleasantness was not mediated by odor referral. These results indicate that as an
      odor-taste mixture approximates a mental representation of a familiar food, its
      components are increasingly merged into one perceptual object sensed in the
      mouth. In parallel, the mixture is evaluated as increasingly pleasant, which
      promotes consumption of familiar foods that have been determined through
      experience to be non-toxic. While the modulatory role of congruency on
      pleasantness and odor referral was confirmed, our results also indicate that
      these effects arise through distinct perceptual mechanisms.

PMID- 29447998
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 receiving PC-FACS, please encourage
      them to join the AAHPM at aahpm.org. Comments from readers are welcomed at pc
      facs@aahpm.org.

PMID- 29447999
TI  - Late heartbeat-evoked potentials are associated with survival after cardiac
      arrest.
AB  - RATIONALE: Cardiac arrest (CA) is a serious condition characterized by high
      mortality rates, even after initial successful resuscitation, mainly due to
      neurological damage. Whether brain-heart communication is associated with outcome
      after CA is unknown. Heartbeat-evoked brain potentials (HEPs) represent
      neurophysiological indicators of brain-heart communication. The aim of this study
      was to address the association between HEPs and survival after CA. METHODS: HEPs
      were calculated from resting EEG/ECG in 55 CA patients 24 h after resuscitation.
      All patients were treated with targeted temperature management and a standardized
      sedation protocol during assessment. We investigated the association between HEP
      amplitude (180-320 ms, 455-595 ms, 860-1000 ms) and 6-month survival. RESULTS:
      Twenty-five of 55 patients (45%) were still alive at 6-month follow-up. Survivors
      showed a higher HEP amplitude at frontopolar and frontal electrodes in the late
      HEP interval than non-survivors. This effect remained significant after
      controlling for between-group differences in terms of age, Fentanyl dose, and
      time lag between resuscitation and EEG assessment. There were no group
      differences in heart rate or heart rate variability. CONCLUSION: Brain-heart
      communication, as reflected by HEPs, is associated with survival after CA. Future
      studies should address the brain-heart axis in CA.

PMID- 29448000
TI  - Bone marrow-derived fibrocytes promote stem cell-like properties of lung cancer
      cells.
AB  - Cancer stem cells (CSCs) represent a minor population that have clonal tumor
      initiation and self-renewal capacity and are responsible for tumor initiation,
      metastasis, and therapeutic resistance. CSCs reside in niches, which are composed
      of diverse types of stromal cells and extracellular matrix components. These
      stromal cells regulate CSC-like properties by providing secreted factors or by
      physical contact. Fibrocytes are differentiated from bone marrow-derived CD14+
      monocytes and have features of both macrophages and fibroblasts. Accumulating
      evidence has suggested that stromal fibrocytes might promote cancer progression.
      However, the role of fibrocytes in the CSC niches has not been revealed. We
      herein report that human fibrocytes enhanced the CSC-like properties of lung
      cancer cells through secreted factors, including osteopontin, CC-chemokine ligand
      18, and plasminogen activator inhibitor-1. The PIK3K/AKT pathway was critical for
      fibrocytes to mediate the CSC-like functions of lung cancer cells. In human lung
      cancer specimens, the number of tumor-infiltrated fibrocytes was correlated with
      high expression of CSC-associated protein in cancer cells. These results suggest
      that fibrocytes may be a novel cell population that regulates the CSC-like
      properties of lung cancer cells in the CSC niches.

PMID- 29448001
TI  - Induced pluripotent stem cells (iPSC)-derived retinal cells in disease modeling
      and regenerative medicine.
AB  - Retinal degenerative disorders are a leading cause of the inherited, irreversible
      and incurable vision loss. While various rodent model systems have provided
      crucial information in this direction, lack of disease-relevant tissue
      availability and species-specific differences have proven to be a major
      roadblock. Human induced pluripotent stem cells (iPSC) have opened up a whole new
      avenue of possibilities not just in understanding the disease mechanism but also
      potential therapeutic approaches towards a cure. In this review, we have
      summarized recent advances in the methods of deriving retinal cell types from
      iPSCs which can serve as a renewable source of disease-relevant cell population
      for basic as well as translational studies. We also provide an overview of the
      ongoing efforts towards developing a suitable in vitro model for modeling retinal
      degenerative diseases. This basic understanding in turn has contributed to
      advances in translational goals such as drug screening and cell-replacement
      therapies. Furthermore we discuss gene editing approaches for autologous repair
      of genetic disorders and allogeneic transplantation of stem cell-based retinal
      derivatives for degenerative disorders with an ultimate goal to restore vision.
      It is pertinent to note however, that these exciting new developments throw up
      several challenges that need to be overcome before their full clinical potential
      can be realized.

PMID- 29448002
TI  - GDF11 expression in the adult rat central nervous system.
AB  - Growth differentiation factor 11 (GDF11), also known as bone morphogenetic
      protein 11 (BMP11), is a member of the transforming growth factor beta (TGF-beta)
      superfamily. Although GDF11 plays pivotal roles during development, including
      anterior/posterior patterning, formation of the kidney, stomach, spleen and
      endocrine pancreas, little information is available for GDF11 expression in the
      adult central nervous system (CNS). We, thus, investigated GDF11 expression in
      the adult rat CNS using immunohistochemistry. GDF11 was intensely expressed in
      most neurons and their axons. Furthermore, we found that astrocytes and ependymal
      cells also express GDF11 protein. These data indicate that GDF11 is widely
      expressed throughout the adult CNS, and its abundant expression in the adult
      brain strongly supports the idea that GDF11 plays important roles in the adult
      brain.

PMID- 29448003
TI  - Increased hippocampal-prefrontal functional connectivity in insomnia.
AB  - Insomnia Disorder (ID) is the second-most common mental disorder and has a far
      reaching impact on daytime functioning. A meta-analysis indicates that, of all
      cognitive domains, declarative memory involving the hippocampus is most affected
      in insomnia. Hippocampal functioning has consistently been shown to be sensitive
      to experimental sleep deprivation. Insomnia however differs from sleep
      deprivation in many aspects, and findings on hippocampal structure and function
      have been equivocal. The present study used both structural and resting-state
      functional Magnetic Resonance Imaging in a larger sample than previously reported
      to evaluate hippocampal volume and functional connectivity in ID. Included were
      65 ID patients (mean age = 48.3 y +/- 14.0, 17 males) and 65 good sleepers (mean
      age = 44.1 y +/- 15.2, 23 males). Insomnia severity was assessed with the
      Insomnia Severity Index (ISI), subjective sleep with the Consensus Sleep Diary
      (CSD) and objective sleep by two nights of polysomnography (PSG). Seed-based
      analysis showed a significantly stronger connectivity of the bilateral
      hippocampus with the left middle frontal gyrus in ID than in controls (p = .035,
      cluster based correction for multiple comparisons). Further analyses across all
      participants moreover showed that individual differences in the strength of this
      connectivity were associated with insomnia severity (ISI, r = 0.371, p = 9.3e-5)
      and with subjective sleep quality (CSD sleep efficiency, r = -0.307, p = .009)
      (all p FDR-corrected). Hippocampal volume did not differ between ID and controls.
      The findings indicate more severe insomnia and worse sleep quality in people with
      a stronger functional connectivity between the bilateral hippocampus and the left
      middle frontal gyrus, part of a circuit that characteristically activates with
      maladaptive rumination and deactivates with sleep.

PMID- 29448004
TI  - Corrigendum to "Energy landscape of the intact and destabilized FMO antennas from
      C. tepidum and the L122Q mutant: Low temperature spectroscopy and modeling study"
      [Biochim. Biophys. Acta Bioenerg. 1859 (2018) 165-173].

PMID- 29448005
TI  - Ratio of muscle mass to fat mass assessed by bioelectrical impedance analysis is
      significantly correlated with liver fat accumulation in patients with type 2
      diabetes mellitus.
AB  - AIMS: Obesity and ectopic fat accumulation are important conditions of type 2
      diabetes mellitus (T2DM). Our aim was to determine whether bioelectrical
      impedance body composition analysis combined with blood test results could
      estimate liver ectopic fat accumulation in patients with treatment-naive T2DM.
      METHODS: Subjects were 119 untreated T2DM patients. Computed tomography scans
      were performed to calculate the liver to spleen attenuation ratio (L/S ratio) as
      a measure of liver fat accumulation, with excess liver fat accumulation defined
      as an L/S ratio <1.0. Elementary body composition was measured by bioelectrical
      impedance analysis using InBody770. RESULTS: The Nagelkerke R2 test showed that
      the muscle mass/fat mass ratio (muscle/fat ratio) was the most suitable variable
      among anthropometric factors and body component indexes for estimating liver fat
      accumulation. The muscle/fat ratio was significantly correlated with the L/S
      ratio (rho = 0.4386, P < 0.0001). Multivariable logistic regression analysis
      showed that the muscle/fat ratio (odds ratio 0.40, 95% confidence interval 0.22
      0.73, P < 0.01) and alanine aminotransferase (odds ratio 1.06, 95% confidence
      interval 1.02-1.10, P < 0.01) were independently and significantly associated
      with liver fat accumulation. In receiver operating characteristic curve analysis,
      the cutoff value of the muscle/fat ratio for excess liver fat accumulation was
      2.34. CONCLUSION: In patients with treatment-naive T2DM, the muscle/fat ratio and
      ALT are useful for estimating the presence of excess liver fat accumulation in
      daily clinical practice.

PMID- 29448006
TI  - Plasma triglycerides as a risk factor for chronic kidney disease in type 2
      diabetes mellitus: Evidence from northeastern Thailand.
AB  - AIMS: To investigate the observational association between plasma triglyceride
      and CKD in patients with T2DM. METHODS: A hospital-based retrospective registry
      was used to obtain data of 3,748 T2DM patients from May 2016 to October 2016.
      Anthropometric measurements and biochemical reports of T2DM patients with CKD
      were obtained by data extraction of medical records. CKD was defined according to
      the estimated glomerular filtration rate (eGFR< 60 mL/min/1.73 m2). Multiple
      logistic regression was used to determine the association between plasma
      triglyceride and CKD. RESULTS: The mean age of the participants was 61.4 +/- 11.0
      years, and a majority of them was female (64%) with poor glycemic control (83%),
      increased plasma triglyceride (51%) and 27% of T2DM patients had CKD. There was a
      significant trend towards deteriorating renal function (lower eGFR) with
      categorically raised triglyceride levels. After controlling for age, sex and
      other confounders, 'borderline high' (adjusted odds ratio (OR): 1.24, 95%
      confidence interval (CI): 1.01-1.54), 'high' (adjusted OR: 1.52, 95% CI: 1.24
      1.85) and 'very high' (adjusted OR: 3.40, 95% CI: 1.94-5.94) triglyceride level
      groups had higher likelihood to have CKD compared to normal triglyceride level.
      CONCLUSION: CKD was associated with a higher level of plasma triglyceride among
      patients with T2DM. These results support the rationale to screen and manage
      increased triglyceride in routine clinical practices among persons with diabetes
      to prevent CKD.

PMID- 29448007
TI  - Dysfunction of CD3-CD16+CD56dim and CD3-CD16-CD56bright NK cell subsets in RR-MS
      patients.

PMID- 29448008
TI  - Insecticidal activity, putative binding proteins and histopathological effects of
      Bacillus thuringiensis Vip3(459) toxin on the lepidopteran pest Ectomyelois
      ceratoniae.
AB  - The carob moth, Ectomyelois ceratoniae, is an important agricultural pest that is
      susceptible to the Vip3(459) protein. The insecticidal activity, evaluated
      against this lepidopteran pest, displayed an LC50 value of about 28 ng/cm2. The
      investigation of the mode of action of this B. thuringiensis protein demonstrated
      that the active form of this toxin bound to putative receptors in the BBMV of E.
      ceratoniae. Ligand blotting experiment proved that Vip3(459) specifically bound
      to two proteins of about 53 and 57 kDa, located on the midgut. This specific
      binding caused perturbations in midgut tissues. The histopathology of 20 midguts
      from Vip3(459)-feeding larvae showed cytoplasm vacuolization, brush border
      membrane destruction, vesicle formation in the apical region and cellular
      disintegration. These findings suggested that B. thuringiensis Vip3(459) could be
      a promising biocontrol agent to eradicate E. ceratoniae and to prevent emergence
      of resistance.

PMID- 29448009
TI  - OpenStreetMap data for alcohol research: Reliability assessment and quality
      indicators.
AB  - There is a growing interest in using OpenStreetMap [OSM] data in health research.
      We evaluate the usefulness of OSM data for researching the spatial availability
      of alcohol, a field which has been hampered by data access difficulties. We find
      OSM data is about 50% complete, which appears adequate for replicating findings
      from other studies using alcohol licensing data. Further, we show how OSM quality
      metrics can be used to select areas with more complete alcohol data. The ease of
      access and use may create opportunities for analysts and researchers seeking to
      understand broad patterns of alcohol availability.

PMID- 29448010
TI  - Improved Outcomes in Management of Hypoplastic Left Heart Syndrome Associated
      With Congenital Diaphragmatic Hernia: an Algorithmic Approach.
AB  - Hypoplastic left heart syndrome (HLHS) is the second most common congenital heart
      disease associated with congenital diaphragmatic hernia (CDH). The reported
      survival rate of neonates with CDH and HLHS is only 1%-5%. We review our
      experience with CDH and HLHS and compare our outcomes with published literature.
      Retrospective review of all neonates with CDH and HLHS at our institution over a
      10-year period was performed. The morphology of cardiac and diaphragm defects,
      clinical course, treatment strategies, and outcomes were reviewed, and an
      algorithmic approach was proposed. Five patients with CDH and HLHS were treated
      between 2006 and 2016. All had mitral stenosis with aortic stenosis. Four
      patients had a left-sided Bochdalek diaphragmatic hernia and 1 patient had a
      large bilateral Morgagni hernia. Two (2/4) of the Bochdalek hernias were
      associated with significant pulmonary hypoplasia and required patch closure of
      the CDH; both were palliated with percutaneous ductal stents and both died. Three
      patients underwent primary Norwood operation followed by repair of less severe
      CDH defect. All 3 patients are currently well and have survived bidirectional
      Glenn anastomosis; one patient is well after Fontan operation. Successful
      palliation of neonates with HLHS and associated CDH is possible in the current
      era. Outcome is determined primarily by the severity of the CDH and the degree of
      associated pulmonary hypoplasia. An algorithmic team approach is helpful in
      management of this difficult group of patients.

PMID- 29448011
TI  - Oceanographic upwelling conditions influence signaling pathways involved in
      muscle growth of intertidal fish.
AB  - Few studies have addressed the impact of the upwelling oceanographical conditions
      on biological processes, such as growth, using a molecular and physiological
      approach. Upwelling conditions are characterized by low temperature seawater and
      high nutrient availability, which represents an ideal opportunity to understand
      how habitat modulates animal performance at different levels of biological
      complexity. We aimed to assess intraspecific variations in weight, oxygen
      consumption, protein content, and key signaling pathways involved in muscle
      growth (protein kinase B (AKT) and extracellular signal-regulated kinase (ERK))
      under experimental trials considering high/low seawater temperatures with
      full/restricted food rations. For this purpose, we studied Girella laevifrons,
      one of the most abundant fish species inhabiting rocky intertidal zones along the
      Eastern South Pacific coasts. Using fish obtained from upwelling (U) and non
      upwelling (NU) zones, we reported that U animals displayed higher growth
      performance during both contrasting trials, with a weight gain (~3 g), lower
      oxygen consumption (~12%), and higher protein contents (~20%). Only ERK showed
      significant differences during the trials (~2-fold downregulation between NU and
      U fish). We also found that U fish increased protein ubiquitination in high water
      temperature and restricted food ration in contrast to NU fish. Our results help
      to elucidate how upwelling conditions may influence fish growth at physiological
      and molecular levels. Still, future analyses are necessary to improve the
      information regarding the impact of U and NU condition on animals, as well as the
      possible applications of this data in the aquaculture industry.

PMID- 29448012
TI  - Clogging in staked-in needle pre-filled syringes (SIN-PFS): Influence of water
      vapor transmission through the needle shield.
AB  - Staked-in needle pre-fillable syringes (SIN-PFS) are a convenient delivery system
      widely established in the growing pharmaceutical market. Under specific storage
      conditions, the needle of PFS containing high concentration drug product (DP)
      solution is prone to clogging, which prevents administration of the liquid. The
      purpose of this study is to clarify the clogging phenomenon of SIN-PFS and to
      elucidate the role of water vapor transmission via the needle shield. The
      presence of liquid within needles is a prerequisite condition for clogging and
      was investigated non-invasively by neutron imaging (NI) to confirm that liquid
      can migrate into the needle under certain processing conditions. The water vapor
      transmission rate (WVTR) of different needle shields was measured and the impact
      of temperature and relative humidity (rH) on the WVTR was investigated on sheets
      with the same composition as used in commercial needle shields. Our study clearly
      showed that the partial vapor pressure difference (DeltaPP) across the needle
      shield is the dominant driving factor for water vapor transmission. A linear
      correlation between DeltaPP and WVTR was found and a model to predict the water
      vapor transmission for PFS under specific storage conditions was developed. The
      impact of the WVTR on needle clogging was confirmed by clogging tests performed
      on SIN-PFS stored under different conditions. Thereby, we clearly show that high
      water loss induced by higher WVTR can be correlated to an increased occurrence of
      needle clogging. In conclusion, the WVTR of the needle shield plays a key role in
      needle clogging and the established WVTR model can be employed to assess the
      clogging risk for product development.

PMID- 29448013
TI  - Antibiotic resistance and molecular characterization of shigella isolates
      recovered from children aged less than 5 years in Manhica, Southern Mozambique.
AB  - The objective of this study was to assess antibiotic resistance and the molecular
      epidemiology of shigella isolates from a case-control study of diarrhoea,
      conducted from 2007 to 2012 in children aged less than 5 years in Manhica
      district, southern Mozambique. All isolates were tested for antimicrobial
      susceptibility using the disc diffusion method. Polymerase chain reaction was
      used to detect different molecular mechanisms of antibiotic resistance.
      Serotyping was performed using specific antisera. The clonal relationship of
      Shigella flexneri and Shigella sonnei was assessed by pulsed-field gel
      electrophoresis (PFGE). Of the 67 shigella isolates analysed, 59 were diarrhoeal
      cases and eight were controls. S. flexneri (70.1%; 47/67) was the most common
      species, followed by S. sonnei (23.9%; 16/67). The most prevalent S. flexneri
      serotypes were 2a (38.3%; 18/47), 6 (19.2%; 9/47) and 1b (14.9%; 7/47). High
      rates of antimicrobial resistance were observed for trimethoprim-sulfametoxazole
      (92.5%; 62/67), tetracycline (68.7%; 46/67), chloramphenicol (53.7%; 36/67) and
      ampicillin (50.7%; 34/67). Multi-drug resistance (MDR) was present in 55.2%
      (37/67) of the isolates and was associated with a case fatality rate of 8.1%
      (3/37). PFGE revealed 22 clones (16 S. flexneri and 6 S. sonnei), among which P1
      (31.9%; 15/47), P9 (17%; 8/47) and P2 (10.6%; 5/47) were the most prevalent
      clones of S. flexneri. In conclusion, S. flexneri was the most prevalent species,
      with MDR isolates mainly belonging to three specific clones (P1, P9 and P2). The
      case fatality rate observed among MDR isolates is a matter of concern, indicating
      the need for appropriate treatment.

PMID- 29448015
TI  - Irregularity and lack of p waves in short tachycardia episodes predict atrial
      fibrillation and ischemic stroke.
AB  - BACKGROUND: Atrial fibrillation (AF) is defined as an irregular supraventricular
      tachycardia (SVT) without p waves, with duration >30 seconds. Whether AF
      characteristics during short SVT episodes predict AF and stroke is not known.
      OBJECTIVE: The purpose of this study was to determine whether irregularity and
      lack of p waves, alone or in combination, during short SVT episodes increase the
      risk of incident AF and ischemic stroke. METHODS: The population-based Malmo Diet
      and Cancer study includes 24-hour ECG screening of 377 AF-free individuals (mean
      age 64.5 years; 43% men) who were prospectively followed for >13 years. There
      were 65 AF events and 25 ischemic stroke events during follow-up. Subjects with
      an SVT episode >=5 beats were identified, and the longest SVT episode was
      assessed for irregularity and lack of p waves. The association between SVT
      classification and AF and stroke was assessed using multivariable adjusted Cox
      regression. RESULTS: The incidence of AF increased with increasing abnormality of
      the SVTs. The risk-factor adjusted hazard ratio for AF was 4.95 (95% confidence
      interval 2.06-11.9; P <.0001) for those with short irregular SVTs (<70 beats)
      without p waves. The incidence of ischemic stroke was highest in the group with
      regular SVT episodes without p waves (hazard ratio 14.2; 95% confidence interval
      3.76-57.6; P <.0001, adjusted for age and sex). CONCLUSION: Characteristics of
      short SVT episodes detected at 24-hour ECG screening are associated with incident
      AF and ischemic stroke. Short irregular SVTs without p waves likely represent
      early stages of AF or atrial myopathy. Twenty-four-hour ECG could identify
      subjects suitable for primary prevention efforts.

PMID- 29448014
TI  - Intrauterine inflammation reduces postnatal neurogenesis in the hippocampal
      subgranular zone and leads to accumulation of hilar ectopic granule cells.
AB  - Prenatal inflammation is associated with poor neurobehavioral outcomes in exposed
      offspring. A common route of exposure for the fetus is intrauterine infection,
      which is often associated with preterm birth. Hippocampal development may be
      particularly vulnerable to an inflammatory insult during pregnancy as this region
      remains highly neurogenic both prenatally and postnatally. These studies sought
      to determine if intrauterine inflammation specifically altered hippocampal
      neurogenesis and migration of newly produced granule neurons during the early
      postnatal period. Microglial and astroglial cell populations known to play a role
      in the regulation of postnatal neurogenesis were also examined. We show that
      intrauterine inflammation significantly reduced hippocampal neurogenesis between
      postnatal days 7 (P7) and P14 as well as decreased granule cell density at P28.
      Ectopic migration of granule cells was observed in LPS-exposed mice at P14, but
      not at P28. Intrauterine inflammation had no effect on hippocampal astrocyte or
      microglia density or on apoptosis rate at the postnatal time points examined.
      Thus, exposure to intrauterine inflammation disrupts early postnatal neurogenesis
      and leads to aberrant migration of newly born granule cells.

PMID- 29448016
TI  - Intestinal immunity suppresses carrying capacity of rats for the model tapeworm,
      Hymenolepis diminuta.
AB  - Hymenolepis diminuta is a parasitic tapeworm of the rat small intestine and is
      recognized as a useful model for the analysis of cestode-host interactions. In
      this study, we analyzed factors affecting the biomass of the tapeworm through use
      of rat strains carrying genetic mutations, namely X-linked severe combined
      immunodeficiency (xscid; T, B and NK cells deficiency), nude (rnu; T cell
      deficiency), and mast cell deficient rats. The worm biomass of F344-xscid rats
      after infection with 5 cysticercoids was much larger than control F344 rats from
      3 to 8 weeks. The biomass of F344-rnu rats was also larger than the controls, but
      was intermediate between F344-xscid and control rats. These observations
      demonstrated that host immunity can control the maximal tapeworm biomass, i.e.,
      carrying capacity, of the rat small intestine. Both T cell and other immune cells
      (B and NK cells) have roles in determining the carrying capacity of tapeworms.
      Total worm biomass and worm numbers in mast cell deficient rats (WsRC-Ws/Ws) were
      not significantly different from control WsRC-+/+ rats after 3 and 6 weeks of
      primary infection. Mast cell deficient rats displayed reinfection resistance for
      worm biomass but not worm expulsion. These findings suggest that the mast cell
      has a role for controlling the biomass of this tapeworm in reinfection alone, but
      does not affect the rate of worm expulsion. Overall, our findings indicate that
      the mast cell is not a major effector cell for the control of the carrying
      capacity of tapeworms. The identity of the major effector cell remains unknown.

PMID- 29448017
TI  - Fetal bovine serum-free cryopreservation methods for clinical banking of human
      adipose-derived stem cells.
AB  - The use of fetal bovine serum (FBS) as a cryopreservation supplement is not
      suitable for the banking of mesenchymal stem cells (MSCs) due to the risk of
      transmission of disease as well as xenogeneic immune reactions in the
      transplanted host. Here, we investigated if human serum albumin (HSA), human
      serum (HS), or knockout serum replacement (KSR) can replace FBS for the
      cryopreservation of MSCs. In addition, we examined the characteristics of MSCs
      after multiple rounds of cryopreservation. Human adipose-derived stem cells
      (ASCs) cryopreserved with three FBS replacements, 9% HSA, 90% HS, or 90% KSR, in
      combination with 10% dimethyl sulfoxide (Me2SO) maintained stem cell properties
      including growth, immunophenotypes, gene expression patterns, and the potential
      to differentiate into adipogenic, osteogenic, and chondrogenic lineages, similar
      to ASCs frozen with FBS. Moreover, the immunophenotype, gene expression, and
      differentiation capabilities of ASCs were not altered by up to four freeze-thaw
      cycles. However, the performance of three or four freeze-thaw cycles
      significantly reduced the proliferation ability of ASCs, as indicated by the
      longer population doubling time and reduced colony-forming unit-fibroblast
      frequency. Together, our results suggest that HSA, HS, or KSR can replace FBS for
      the cryopreservation of ASCs, without altering their stemness, and should be
      processed with no more than two freeze-thaw cycles for clinical approaches.

PMID- 29448018
TI  - Applications of gray-level variation detection method to intracellular ice
      formation.
AB  - Intracellular ice formation (IIF) is the major cause of death in cells subjected
      to freezing. The occurrence of intracellular ice prevents the penetration of
      light into the camera and makes the image dark. Therefore, the gray-level
      variation can reflect the IIF. However, cell deformation is accompanied with IIF,
      especially for larger cells. It is necessary to account this entire phenomenon
      together in a single method. In this paper, the normalized parameter C defined by
      the gray-level variation depending on the displacement was defined to reflect the
      gray-level change of each pixel point in the region of interest of the image. The
      process of IIF of onion epidermal cells and 293T cells was analyzed by this
      method.

PMID- 29448019
TI  - Recovery of black-necked swans, macrophytes and water quality in a Ramsar wetland
      of southern Chile: Assessing resilience following sudden anthropogenic
      disturbances.
AB  - In 2004 migration and mortality for unknown reasons of the herbivorous Black
      necked swan (Cygnus melancorhyphus (Molina, 1782)) occurred within the Rio Cruces
      wetland (southern Chile), a Ramsar Site and nature sanctuary. Before 2004, this
      wetland hosted the largest breeding population of this water bird in the
      Neotropic Realm. The concurrent decrease in the spatial occurrence of the aquatic
      plant Egeria densa Planch. 1849 - the main food source of swans - was proposed as
      a cause for swan migration and mortality. Additionally, post-mortem analyses
      carried out on swans during 2004 showed diminished body weight, high iron loads
      and histopathological abnormalities in their livers, suggesting iron storage
      disease. Various hypotheses were postulated to describe those changes; the most
      plausible related to variations in water quality after a pulp mill located
      upstream the wetland started to operate in February 2004. Those changes cascaded
      throughout the stands of E. densa whose remnants had high iron contents in their
      tissues. Here we present results of a long-term monitoring program of the wetland
      components, which show that swan population abundance, body weights and
      histological liver conditions recovered to pre-disturbance levels in 2012. The
      recovery of E. densa and iron content in plants throughout the wetland, also
      returned to pre-disturbance levels in the same 8-year time period. These results
      show the temporal scale over which resilience and natural restoring processes
      occur in wetland ecosystems of temperate regions such as southern Chile.

PMID- 29448020
TI  - An anaerobic membrane bioreactor - membrane distillation hybrid system for energy
      recovery and water reuse: Removal performance of organic carbon, nutrients, and
      trace organic contaminants.
AB  - In this study, a direct contact membrane distillation (MD) unit was integrated
      with an anaerobic membrane bioreactor (AnMBR) to simultaneously recover energy
      and produce high quality water for reuse from wastewater. Results show that AnMBR
      could produce 0.3-0.5L/g CODadded biogas with a stable methane content of
      approximately 65%. By integrating MD with AnMBR, bulk organic matter and
      phosphate were almost completely removed. The removal of the 26 selected trace
      organic contaminants by AnMBR was compound specific, but the MD process could
      complement AnMBR removal, leading to an overall efficiency from 76% to complete
      removal by the integrated system. The results also show that, due to complete
      retention, organic matter (such as humic-like and protein-like substances) and
      inorganic salts accumulated in the MD feed solution and therefore resulted in
      significant fouling of the MD unit. As a result, the water flux of the MD process
      decreased continuously. Nevertheless, membrane pore wetting was not observed
      throughout the operation.

PMID- 29448021
TI  - Risk assessment of silica nanoparticles on liver injury in metabolic syndrome
      mice induced by fructose.
AB  - This study aims to assess the effects and the mechanisms of silica nanoparticles
      (SiNPs) on hepatotoxicity in both normal and metabolic syndrome mouse models
      induced by fructose. Here, we found that SiNPs exposure lead to improved insulin
      resistance in metabolic syndrome mice, but markedly worsened hepatic ballooning,
      inflammation infiltration, and fibrosis. Moreover, SiNPs exposure aggravated
      liver injury in metabolic syndrome mice by causing serious DNA damage. Following
      SiNPs exposure, liver superoxide dismutase and catalase activities in metabolic
      syndrome mice were stimulated, which is accompanied by significantly increased
      malondialdehyde and 8-hydroxy-2-deoxyguanosine levels as compared to normal mice.
      Scanning electron microscope (SEM) revealed that SiNPs were more readily
      deposited in the liver mitochondria of metabolic syndrome mice, resulting in more
      severe mitochondrial injury as compared to normal mice. We speculated that SiNPs
      induced mitochondrial injury might be the cause of hepatic oxidative stress,
      which further lead to a series of liver lesions as observed in mice following
      SiNPs exposure. Based on these results, it is likely that SiNPs will increase the
      risk and severity of liver disease in individuals with metabolic syndrome.
      Therefore, SiNPs should be used cautiously in food additives and clinical
      settings.

PMID- 29448022
TI  - Photosynthesis and mineralogy of Jania rubens at low pH/high pCO2: A future
      perspective.
AB  - Corallinales (Rhodophyta) are high Mg-calcite macroalgae and are considered among
      the most vulnerable organisms to ocean acidification (OA). These sensitive
      species play fundamental roles in coastal systems as food source and settlement
      promoters as well as being involved in reef stabilization, and water carbonate
      balance. At present only a few studies are focused on erect calcifying macroalgae
      under low pH/high pCO2 and the contrasting results make difficult to predict the
      ecological consequences of the OA on the coralline algae. In this paper the
      physiological reasons behind the resistance of Jania rubens, one of the most
      common calcareous species, to changing ocean pH are analysed. In particular, we
      studied the photosynthetic and mineralogical response of J. rubens after a three
      week transplant in a natural CO2 vent system. The overall results showed that J.
      rubens could be able to survive under predicted pH conditions even though with a
      reduced fitness; nevertheless physiological limits prevent the growth and
      survival of the species at pH6.7. At low pH (i.e. pH7.5), the maximum and
      effective PSII efficiency decreased even if the increase of Rubisco expression
      suggests a compensation effort of the species to cope with the decreased light
      driven products. In these circumstances, a pH-driven bleaching phenomenon was
      also observed. Even though the photosynthesis decreased at low pH, J. rubens
      maintained unchanged the mineralogical composition and the carbonate content in
      the cell wall, suggesting that the calcification process may also have a
      physiological relevance in addition to a structural and/or a protective role.
      Further studies will confirm the hypotheses on the functional and evolutionary
      role of the calcification process in coralline algae and on the ecological
      consequences of the community composition changes under high pCO2 oceans.

PMID- 29448023
TI  - Simulating spatial distribution of coastal soil carbon content using a
      comprehensive land surface factor system based on remote sensing.
AB  - Surface soil carbon content (SCC) in coastal area is affected by complex factors,
      and revealing the SCC spatial distribution is considerably significant for
      judging the quantity of stored carbon and identifying the driving factors of SCC
      variation. A comprehensive land surface factor system (CLSFS) was established; it
      utilized the ecological significances of remote sensing data and included four
      class factors, namely, spectrum information, ecological indices, spatial
      location, and land cover. Different simulation algorithms, including single
      factor regression (SFR), multiple-factor regression (MFR), partial least squares
      regression (PLSR), and back propagation neural network (BPNN), were adopted to
      conduct the surface (0-30cm) SCC mapping in the Yellow River Delta in China, and
      a 10-fold cross validation approach was used to validate the uncertainty and
      accuracy of the algorithms. The results indicated that the mean simulated
      standard deviations were all <0.5g/kg and thus showed a low uncertainty; the mean
      root mean squared errors based on the simulated and measured SCC were 3.88g/kg
      (SFR), 3.85g/kg (PLSR), 3.67g/kg (MFR), and 2.78g/kg (BPNN) with the BPNN
      exhibiting a high accuracy compared to similar studies. The mean SCC was
      17.40g/kg in the Yellow River Delta with distinct spatial heterogeneity; in
      general, the SCC in the alongshore regions, except for estuaries, was low, and
      that in the west of the study area was high. The mean SCCs in farmland
      (18.31g/kg) and wetland vegetation (17.98g/kg) were higher than those in water
      area (16.07g/kg), saltern (15.61g/kg), and bare land (14.71g/kg). Land-sea
      interaction and human activity jointly affected the SCC spatial distribution. The
      CLSFS was proven to have good applicability, and can be widely used in simulating
      the SCC spatial distribution in coastal areas.

PMID- 29448024
TI  - How to avoid eutrophication in coastal seas? A new approach to derive river
      specific combined nitrate and phosphate maximum concentrations.
AB  - Since 1950, increase in nitrogen (N) and phosphorus (P) river loadings in the
      North-East Atlantic (NEA) continental seas has induced a deep change in the
      marine coastal ecosystems, leading to eutrophication symptoms in some areas. In
      order to recover a Good Ecological Status (GES) in the NEA, as required by
      European Water Framework Directive (WFD) and Marine Strategy Framework Directive
      (MSFD), reductions in N- and P-river loadings are necessary but they need to be
      minimal due to their economic impact on the farming industry. In the frame of the
      "EMoSEM" European project, we used two marine 3D ecological models (ECO-MARS3D,
      MIRO&CO) covering the Bay of Biscay, the English Channel and the southern North
      Sea to estimate the contributions of various sources (riverine, oceanic and
      atmospheric) to the winter nitrate and phosphate marine concentrations. The
      various distributed descriptors provided by the simulations allowed also to find
      a log-linear relationship between the 90th percentile of satellite-derived
      chlorophyll concentrations and the "fully bioavailable" nutrients, i.e. simulated
      nutrient concentrations weighted by light and stoichiometric limitation factors.
      Any GES threshold on the 90th percentile of marine chlorophyll concentration can
      then be translated in maximum admissible 'fully bioavailable' DIN and DIP
      concentrations, from which an iterative linear optimization method can compute
      river-specific minimal abatements of N and P loadings. The method has been
      applied to four major river groups, assuming either a conservative (8MUgChlL-1)
      or a more socially acceptable (15MUgChlL-1) GES chlorophyll concentration
      threshold. In the conservative case, maximum admissible winter concentrations for
      nutrients correspond to marine background values, whereas in the lenient case,
      they are close to values recommended by the WFD/MSFD. Both models suggest that to
      reach chlorophyll GES, strong reductions of DIN and DIP are required in the
      Eastern French and Belgian-Dutch river groups.

PMID- 29448025
TI  - Remote sensing of the urban heat island effect in a highly populated urban
      agglomeration area in East China.
AB  - Increasingly urban agglomeration, representing a group of cities with a compact
      spatial organization and close economic links, can rise surface temperature in a
      continuous area due to decreasing distance between cities. Significant progress
      has been made in elucidating surface urban heat island intensity (SUHII) of a
      single city or a few big cities, but the SUHII's patterns remain poorly
      understood in urban agglomeration regions. Using Aqua/Terra MODIS data over 2010
      2015, we examined the SUHII variations and their drivers in Yangtze River Delta
      Urban Agglomeration (YRDUA) of east China. Instead of using the widely-used
      suburban/rural areas as references, this study predicted the unaffected reference
      temperature wall-to-wall from natural forests by a simple planar surface model.
      Results indicated that urbanization warmed the land surface regardless of urban
      area size in YRDUA, with the SUHII clearly larger in the day (2.6+/-0.9 degrees
      C) than night (0.7+/-0.4 degrees C). The SUHII varied markedly by cities, yet the
      largest did not happen in the presumed core cities. Also, the SUHII differed
      greatly in a seasonal cycle, with summer-winter difference of 4.2+/-0.9 degrees C
      and 2.0+/-0.5 degrees C in the day and night, respectively. Particularly, cooling
      effects of urban areas were observed in winter for the majority of cities at
      night. These spatiotemporal patterns depend strongly on the background climate
      (precipitation and air temperature), vegetation activity, surface albedo, and
      population density, with contrast mechanisms during the day and night. Further,
      we showed that ignoring urban agglomeration effect (using suburban/rural areas as
      the unaffected references) would lead to large biases of SUHII estimates in terms
      of magnitude and spatial distribution. Our results emphasize the necessity of
      considering cities altogether when assessing the urbanization effects on climate
      in an urban agglomeration area.

PMID- 29448026
TI  - Characterization and source identification of fine particulate matter in urban
      Beijing during the 2015 Spring Festival.
AB  - The Spring Festival (SF) is the most important holiday in China for family
      reunion and tourism. During the 2015 SF an intensive observation campaign of air
      quality was conducted to study the impact of the anthropogenic activities and the
      dynamic characteristics of the sources. During the study period, pollution
      episodes frequently occurred with 12days exceeding the Chinese Ambient Air
      Quality Standards for 24-h average PM2.5 (75MUg/m3), even 8days with exceeding
      150MUg/m3. The daily maximum PM2.5 concentration reached 350MUg/m3 while the
      hourly minimum visibility was <0.8km. Three pollution episodes were selected for
      detailed analysis including chemical characterization and diurnal variation of
      the PM2.5 and its chemical composition, and sources were identified using the
      Positive Matrix Factorization model. The first episode occurring before the SF
      was characterized by more formation of SO42- and NO3- and high crustal enrichment
      factors for Ag, As, Cd, Cu, Hg, Pb, Se and Zn and seven categories of pollution
      sources were identified, whereby vehicle emission contributed 38% to the PM2.5.
      The second episode occurring during the SF was affected heavily by large-scale
      firework emissions, which led to a significant increase in SO42-, Cl-, OC, K and
      Ba; these emissions were the largest contributor to the PM2.5 accounting for 36%.
      During the third episode occurring after the SF, SO42-, NO3-, NH4+ and OC were
      the major constituents of the PM2.5 and the secondary source was the dominant
      source with a contribution of 46%. The results provide a detailed understanding
      on the variation in occurrence, chemical composition and sources of the PM2.5 as
      well as of the gaseous pollutants affected by the change in anthropogenic
      activities in Beijing throughout the SF. They highlight the need for limiting the
      firework emissions during China's most important traditional festival.

PMID- 29448028
TI  - Humoral immune parameters in serum of gilthead seabream (Sparus aurata L.) after
      induced skin injury.
AB  - Skin lesions contribute to significant rates of morbidity and mortality in fish
      because they permit the entry of pathogens. Different seric immune parameters
      (IgM level, protease, antiprotease, peroxidase and lysozyme) and bactericidal
      activity (against Vibrio harveyi and Photobacterium damsealae) of gilthead
      seabream (Sparus aurata L.) specimens were evaluated after experimentally
      wounding fish in two body locations (above or below the lateral line). The
      results demonstrate that the level of several immune parameters present in fish
      serum (IgM, proteases, peroxidase and bactericidal activity) showed statistically
      significant variations depending on the site of the skin wound and the time post
      wounding (from 0 to 7 days). However, other parameters (such as antiproteases or
      lysozyme) remained unaltered during the experiment and did not differs from the
      values recorded on control fish (non-wounded). The highest activities recorded
      coincided with the inflammatory healing phase. Moreover, many more significant
      variations were observed in fish wounded below the lateral line than in those
      wounded above the lateral line. The present results demonstrate the importance of
      skin integrity in the maintenance of fish body homeostasis.

PMID- 29448029
TI  - MicroRNA-874 inhibits TNF-alpha-induced remodeling in human fetal airway smooth
      muscle cells by targeting STAT3.
AB  - Pro-inflammatory cytokines-induced airway remodeling was a significant feature of
      asthma disease. The aim of the present study was to explore the functional
      significance of miR-874 in tumor necrosis factor (TNF)-alpha-treated human fetal
      airway smooth muscle (fASM) cells. Here, we found that TNF-alpha treatment
      significantly down-regulated the expression of miR-874 in fASM cells. MiR-874
      overexpression markedly inhibited cell viability and migration, suppressed the
      expression of PCNA and Ki67, reduced the expression of collagen I and collagen
      III, decreased the expression and activity of matrix metalloproteinase (MMP)-9
      and MMP-2, and induced an obvious elevation of tissue inhibitors of
      metalloproteinases (TIMPs). In addition, the increased production of interleukin
      (IL)-6, IL-8 and eotaxin induced by TNF-alpha were significantly inhibited by miR
      874 overexpression. Signal transducers and activators of transcription (STAT) 3
      was identified as a direct target of miR-874, and STAT3 overexpression partly
      reversed the protective effects of miR-874 against TNF-alpha-induced airway
      remodeling. Overall, these findings demonstrate that miR-874 inhibits TNF-alpha
      induced remodeling in human fASM cells at least in part by targeting STAT3.

PMID- 29448030
TI  - A SEP tag enhances the expression, solubility and yield of recombinant TEV
      protease without altering its activity.
AB  - Tobacco Etch Virus (TEV) protease is used in the purification of recombinant
      proteins, but its usage is often hampered by solubility issues. Here, we report a
      short, 12-residue solubility enhancing peptide (SEP) tag attached at the C
      terminus of TEV (TEV-C9R). We assessed the effects of the C9R tag on the
      biophysical and biochemical characteristics of TEV. The yield of HPLC purified
      TEV-C9R expressed in E. coli grown in 200 mL LB or TB media was between 10 and 13
      mg, which was up to 6.5 times higher than the yield of the untagged TEV (untagged
      TEV). TEV-C9R was active over a pH range of 5-8, which was wider than that of the
      commonly used thrombin, and it remained active upon incubation at 60  degrees C
      much longer than the untagged-TEV, which aggregated at this temperature. Static
      and dynamic light scattering demonstrated the higher solubility of purified TEV
      C9R. Furthermore, the thermal unfolding of TEV-C9R, as assessed by circular
      dichroism at pH 4.7, was almost perfectly reversible, in contrast to that of
      untagged-TEV, which aggregated at high temperature. These results demonstrate the
      improved biophysical and biochemical characteristics of TEV-C9R originating from
      higher solubility and provide another example of how SEP tags can enhance enzyme
      solubility without altering its activity.

PMID- 29448031
TI  - Phylogeography and population genetic analyses reveal the speciation of the Tuber
      indicum complex.
AB  - Tuber indicum is an ectomycorrhizal ascomycete that produces edible ascocarps.
      Based on a number of specimens with known exact origin, we investigate the
      speciation of the Tuber indicum complex in southwest China. Internal transcribed
      spacer (ITS) and simple sequence repeat (SSR) markers were used in the study.
      Phylogeography and population genetics analyses were combined to detect 31 wild
      populations of the T. indicum complex. Two distinct lineages, Tuber cf. indicum
      and Tuber cf. himalayense, were identified in the T. indicum complex that
      exhibited significant phylogeographic structures and genetic differentiation. The
      characteristics of haplotypes distributing along the river demonstrate that the
      diffusion and modern distribution pattern of species was influenced by river
      expansion. These findings are critical for the protection of the diversity of
      truffles in this region.

PMID- 29448032
TI  - Risedronate reduces postoperative bone resorption after cementless total hip
      arthroplasty: A systematic review and meta-analysis.
AB  - OBJECTIVE: To examine the effects of risedronate for reducing periprosthetic bone
      loss after total hip arthroplasty (THA). METHODS: Two reviewers performed an
      electronic literature search for randomized controlled trial (RCTs) evaluating
      the risedronate in the management of periprosthetic bone loss after primary THA.
      The electronic databases include PubMed, Medline, Embase, Web of Science and the
      Cochrane Library from inception to January 2018. We assessed the risk of bias
      using the Cochrane risk-of-bias tool. STATA 14.0 was used to perform the meta
      analysis. RESULTS: Four RCTs were included in our study. Current meta-analysis
      indicated that postoperative reduciton of periprosthetic BMD in the risedronate
      group was significantly lower than that in the placebo group in zones 1, 2, 3, 4,
      6, and 7. There was no increased risk of adverse effects. CONCLUSION: The
      administration of risedronate was associates with a significantly improved
      periprosthetic BMD after primary THA. No increased risk of adverse events were
      observed. Higher quality RCTs are still required for further research.

PMID- 29448033
TI  - Environmental enrichment decreases avoidance responses in the elevated T-maze and
      delta FosB immunoreactivity in anxiety-related brain regions.
AB  - Environmental enrichment (EE) is an animal management technique, which seems to
      improve adaptation to the experimental conditions of housing in laboratory
      animals. Previous studies have pointed to different beneficial effects of the
      procedure in the treatment of several disorders, including psychiatric conditions
      such as depression. The anxiolytic effects induced by EE, on the other hand, are
      not as clear. In fact, it has been proposed that EE acts as a mild stressor
      agent. To better understand the relationship of EE with anxiety-related
      responses, the present study exposed rats to one week of EE and subsequently
      tested these animals in the inhibitory avoidance and escape tasks of the elevated
      T-maze (ETM). In clinical terms, these responses have been respectively related
      to generalized anxiety and panic disorder. All animals were tested in an open
      field, immediately after the ETM, for locomotor activity assessment.
      Additionally, analysis of delta FosB protein immunoreactivity (FosB-ir) was used
      to map areas activated by EE exposure and plasma corticosterone measurements were
      performed. The results obtained demonstrate that exposure to EE for one week
      impaired avoidance responses, an anxiolytic-like effect, without altering escape
      reactions. Also, in animals submitted to the avoidance task EE exposure decreased
      FosB-ir in the cingulate cortex, dorsolateral and intermediate lateral septum,
      hippocampus (cornus of Ammon), anterior and dorsomedial hypothalamus, medial and
      basolateral amygdala and ventral region of the dorsal raphe nucleus. Although no
      behavioral differences were observed in animals submitted to the escape task, EE
      exposure also decreased FosB-ir in the cingulate cortex, hippocampus (dentate
      gyrus), lateral amygdala, paraventricular, anterior and ventromedial
      hypothalamus, dorsomedial periaqueductal gray and ventral and dorsal region of
      the dorsal raphe. No changes in corticosterone levels, however, were observed.
      These results contribute to a better understanding of the effects of EE on
      anxiety.

PMID- 29448034
TI  - Bombyx mori homolog of tumor suppressor p53 is involved in apoptosis-mediated
      antiviral immunity of B. mori cells infected with nucleopolyhedrovirus.
AB  - Apoptosis is important in antiviral immunity and affects viral multiplication and
      pathogenesis. Here, we showed that Bombyx mori cells transiently expressing B.
      mori homolog of the tumor suppressor p53 (Bm-p53) protein underwent apoptosis
      accompanied by elevated caspase-3-like protease activity and processing of B.
      mori Dronc (Bm-Dronc). RNAi-mediated silencing of bm-p53 expression, which
      significantly diminished accumulation of bm-p53 transcript and Bm-p53 protein,
      prevented apoptosis of B. mori cells infected with a recombinant B. mori
      nucleopolyhedrovirus defective in the anti-apoptotic p35 gene (vBmDeltap35) and
      abolished the activation of caspase-3-like protease and processing of Bm-Dronc.
      Apoptosis in vBmDeltap35-infected B. mori cells is associated with viral DNA
      replication, suggesting involvement of the DNA damage response. The Bm-p53 pro
      apoptotic function is also found in Spodoptera frugiperda and Lymantria dispar
      cells. These results indicate that apoptosis induction in vBmDeltap35-infected B.
      mori cells is a Bm-p53-mediated process promoted by the commencement of viral DNA
      replication.

PMID- 29448035
TI  - Nanomedicines and gene therapy for the delivery of growth factors to improve
      perfusion and oxygenation in wound healing.
AB  - Oxygen plays a key role in wound healing, and hypoxia is a major cause of wound
      healing impairment; therefore, treatments to improve hemodynamics and increase
      wound oxygenation are of particular interest for the treatment of chronic wounds.
      This article describes the roles of oxygen and angiogenesis in wound healing as
      well as the tools used to evaluate tissue oxygenation and perfusion and then
      presents a review of nanomedicines and gene therapies designed to improve
      perfusion and oxygenation and accelerate wound healing.

PMID- 29448036
TI  - Molecular characterisation of multidrug-resistant pneumococcal clones colonising
      healthy children in Merida, Venezuela.
AB  - Genetic mechanisms of resistance, clonal composition and the occurrence of pili
      were analysed in 48 multidrug-resistant (MDR) pneumococci isolated from healthy
      children in Merida, Venezuela. Intermediate resistance to penicillin was related
      to variations in pbp2b and pbp2x. High-level resistance to penicillin as well as
      low susceptibility to cephalosporins and carbapenems were associated with
      alterations in pbp1a, pbp2b and pbp2x. Non-beta-lactam resistance was associated
      with Tn3872, Tn5253, Tn6002 and Tn2010 transposons. Macrolide-resistant strains
      carried ermB or mefE, but not mefA. Tetracycline- and chloramphenicol-resistant
      pneumococci carried tetM and cat, respectively. MDR pneumococci were related to
      six clonal complexes (CCs), largely CC156 or CC15. Limited diversity in
      pbp2a,2b,2x-RFLP profiles within each clone was observed. Conversely, detection
      of non-beta-lactam resistance and transposons revealed clear genetic diversity
      within clones. A group of non-typeable/cpsA-negative pneumococci related to the
      null capsule clade 1 (NCC1) carrying a Tn2009 element was found. Each NCC1
      related strain showed a novel MLST allelic combination and a different
      pbp2a,2b,2x-RFLP profile. PI-1 (pilus type 1 rrgC gene) was present in most of
      the MDR pneumococci and its occurrence was commonly homogeneous within each
      clone. PI-1 was present in all CC242 and CC320 pneumococci, whereas it was absent
      in all CC37, CC81 and NCC1 isolates. CC156 and CC15 isolates showed variations in
      the occurrence of PI-1. Both PI-1 and the islet for pilus type 2 were present in
      CC320 isolates. We provide useful data to follow the evolution of clonal
      composition, mechanisms of antibiotic resistance and the occurrence of pili among
      pneumococci circulating in Merida.

PMID- 29448038
TI  - Molecular and biological characterization of a highly pathogenic Trypanosoma
      cruzi strain isolated from a patient with congenital infection.
AB  - Although many Trypanosoma cruzi (T. cruzi) strains isolated from a wide range of
      hosts have been characterized, there is a lack of information about biological
      features from vertically transmitted strains. We describe the molecular and
      biological characteristics of the T. cruzi VD strain isolated from a congenital
      Chagas disease patient. The VD strain was typified as DTU TcVI; in vitro
      sensitivity to nifurtimox (NFX) and beznidazole (BZ) were 2.88 MUM and 6.19 MUM
      respectively, while inhibitory concentrations for intracellular amastigotes were
      0.24 MUM for BZ, and 0.66 MUM for NFX. Biological behavior of VD strain was
      studied in a mouse model of acute infection, resulting in high levels of
      parasitemia and mortality with a rapid clearence of bloodstream trypomastigotes
      when treated with BZ or NFX, preventing mortality and reducing parasitic load and
      intensity of inflammatory infiltrate in skeletal and cardiac muscle. Treatment
      induced parasitological cure, evaluated after immunossupression were 41% and 35%
      for BZ and NFX treatment respectively, suggesting a partial response to these
      drugs in elimination of parasite burden. This exhaustive characterization of this
      T. cruzi strain provides the basis for inclusion of this strain in a panel of
      reference strains for drug screening and adds a new valuable tool for the study
      of experimental T. cruzi infection.

PMID- 29448039
TI  - Development of siRNA mediated RNA interference and functional analysis of novel
      parasitic nematode-specific protein of Setaria digitata.
AB  - Despite the differences of the host, parasitic nematodes may share commonalities
      in their parasitizing genes. Setaria digitata novel protein (SDNP) is such an
      entity which is parasitic nematode-specific and having sequence similarities with
      those of W. bancrofti, B. malayi, Loa loa and Onchocerca volvulus. Post
      transcriptional gene silencing by siRNA mediated RNA interference (RNAi) is a
      widely used technique in functional genomics. Though the technique has been used
      in several free-living, plant and animal parasitic nematodes, it has not yet been
      tried out for the filarial worm S. digitata. In this study, we developed an
      effective siRNA delivery method by microinjection and utilized the siRNAi tool to
      knockdown SDNP to study the phenotypic and cellular changes associated with the
      interference. qPCR analysis revealed, a significant reduction of SDNP transcript
      levels following siRNA microinjection into S. digitata adult worms. Similarly,
      immunohistochemical staining indicated a reduction of SDNP protein expression.
      Furthermore, worms treated with siRNA showed a significant reduction of
      microfilariae release together with embryonic lethality by arresting an early
      developmental stage compared to non-treated worms. A distinct motility reduction
      was also observed in treated worms compared to non-treated counterparts. This is
      the first report of the amenability of S. digitata to the siRNA induced RNAi. The
      presence of inter-domain linkers of muscle-specific twitchin kinase and calcium
      dependent protein kinase isoform CDPK1 together with what our results revealed
      suggest that SDNP is most likely a protein involved in muscle movement and growth
      and development of the nematode. Hence SDNP has the characteristics of a
      potential drug target.

PMID- 29448037
TI  - Quantifying membrane protein oligomerization with fluorescence cross-correlation
      spectroscopy.
AB  - Fluorescence cross-correlation spectroscopy (FCCS) is an advanced fluorescence
      technique that can quantify protein-protein interactions in vivo. Due to the
      dynamic, heterogeneous nature of the membrane, special considerations must be
      made to interpret FCCS data accurately. In this study, we describe a method to
      quantify the oligomerization of membrane proteins tagged with two commonly used
      fluorescent probes, mCherry (mCH) and enhanced green (eGFP) fluorescent proteins.
      A mathematical model is described that relates the relative cross-correlation
      value (fc) to the degree of oligomerization. This treatment accounts for mismatch
      in the confocal volumes, combinatoric effects of using two fluorescent probes,
      and the presence of non-fluorescent probes. Using this model, we calculate a
      ladder of fc values which can be used to determine the oligomer state of membrane
      proteins from live-cell experimental data. Additionally, a probabilistic
      mathematical simulation is described to resolve the affinity of different dimeric
      and oligomeric protein controls.

PMID- 29448040
TI  - Comparing the therapeutic efficacy of different amphotericin B-carrying delivery
      systems against visceral leishmaniasis.
AB  - Amphotericin B (Amp) has been well-successfully used to treat against Leishmania
      infection, although high toxicity has been found in patients. In the present
      study, Amp was administered in Leishmania infantum-infected BALB/c mice by three
      distinct delivery systems aiming to compare their efficacy against challenge
      infection, as well as their side effects in a murine visceral leishmaniasis (VL)
      model. This product was administered in a Poloxamer P407 (Pluronic(r) F127)-based
      polymeric micelle system (Amp/M), in the Ambisome(r) formulation (Lip-Amp) or in
      a free format (free Amp). Glucantime(r) (Gluc) was used as a comparative drug.
      Aiming to evaluate different endpoints of the treatments, the efficacy of the
      compounds was investigated one and 15-days after the therapeutic regimens,
      determining the parasite load by a limiting dilution assay and a quantitative PCR
      (qPCR) technique, as well as evaluating the immune response generated in the
      infected and treated animals. In the results, Amp/M or Lip-Amp-treated mice
      presented the best outcomes, since significant parasite load reductions were
      found in the evaluated organs, as well as a parasite-specific Th1 immune response
      was observed in the animals. In addition, no hepatic or renal damage was found in
      these mice. On the other hand, free Amp or Gluc induced toxicity in the animals,
      which was associated with a low Th1 immune response. Comparatively, Amp/M was the
      most effective drug in our experimental model, and results showed that the Amp
      carrying system could be considered as a future alternative in studies against
      VL.

PMID- 29448041
TI  - VIP changes during daytime in chicken intrinsic choroidal neurons.
AB  - PURPOSE: Ocular autonomic control is mediated by sympathetic and parasympathetic
      nerve fibres. Their interactions are complemented by primary afferent nerve
      fibers of and intrinsic choroidal neurons (ICN). As the vasodilatative
      neuropeptide, vasoactive intestinal peptide (VIP), is expressed in extrinsic and
      intrinsic ocular neurons, it is of special interest in ophthalmic research. Since
      circadian changes of ocular blood flow are known in humans and birds, this study
      aimed at investigating VIP expression at different daytimes in chicken choroid,
      the preferred model species in ICN research. METHODS: 12 eyes of 12 chickens were
      retrieved, slaughtered at 8.00-9.30 a.m. (n = 6) and 8.00 p.m. (n = 6),
      respectively, and choroidal wholemounts were prepared for immunofluorescence of
      VIP. VIP-positive ICN of both groups were quantified and density of VIP-positive
      axons assessed semi-quantitatively. In 28 additional eyes retrieved in the
      morning (n = 14) and evening (n = 14), choroidal VIP content was determined by
      ELISA. Morning and evening data were analyzed statistically. NADPH-diaphorase
      (NADPH-d, ICN cell marker) was done at additional 12 whole mount choroids of 12
      chicken, retrieved in the morning (n = 6) and evening (n = 6). RESULTS: (1)
      Numbers of VIP positive neurons differed significantly between morning: (239.17
      +/- 113.9) and evening: (550.83 +/- 245.7; p = 0.018). (2) Numbers of VIP
      positive perikarya were significantly more accumulated in the temporal part of
      the choroid in the evening than in the morning (p = 0.026). (3) VIP positive axon
      density was found to be similar throughout the choroid in the morning and
      evening. (4) Number of NADPH-d positive neurons was not significantly different
      between morning (848.8 +/- 399.5) and evening (945.8 +/- 622.1, p > 0.05). (5)
      ELISA demonstrated a significant difference of VIP content (p = 0.012) in tissues
      harvested in the morning (145.41 +/- 43.3 pg/ml) compared to evening (221.44 +/-
      106.3 pg/ml). CONCLUSIONS: As VIP positive axon density was similar in the
      morning and the evening throughout the choroid, PPG and ICN seemed to contribute
      equally to the axon network. Yet, changes in the total choroidal VIP content, the
      numbers of VIP positive perikarya, reflecting the intracellular VIP content, and
      their topographical distribution at two different days-times argue for a
      different status of activation of both neuronal sources in contrast to the equal
      amount of NADPHD-d positive neurons. The higher VIP content in the evening,
      compared to the morning, correlates with a known circadian rhythm of a lower IOP
      and a higher choroidal thickness at night. Thus, these changes may argue for a
      potential role of ICN in the regulation of ocular homeostasis and integrity.

PMID- 29448042
TI  - Quantitative comparisons between optical coherence tomography angiography and
      matched histology in the human eye.
AB  - The aim was to quantitatively compare retinal vascular detail as seen on optical
      coherence tomography angiography (OCTA) and matched histology in the human eye.
      13 normal human donor eyes were used. The central retinal artery was cannulated
      after which human packed red blood cells were perfused through the retinal
      vasculature. Retinal vessels were imaged using a custom-built OCTA device during
      red blood cell perfusion. The eye was subsequently perfused with endothelial cell
      antibodies and the flat-mounted retina studied histologically using a confocal
      scanning laser microscope. Qualitative and quantitative comparisons of retinal
      vascular information as seen on OCTA and histology from the same region of
      interest were performed. Gradable OCTA images were acquired from 4 of 13 eyes
      with mean postmortem-to-OCTA imaging time of 4.5 +/- 1.3 h 23 pairs of OCTA
      histology matched images were evaluated. The retinal arteries and veins had
      similar pixel intensity on OCTA images. The diameter of retinal veins was
      significantly greater than its paired artery on OCTA (P < 0.001). The density of
      vascular structures on OCTA (40.2% +/- 10.1%) was significantly less than matched
      histology (52.1% +/- 9.3%, P < 0.001). Mean capillary diameter on OCTA (10.2 +/-
      2.4 MUm) was significantly greater than histology (8.2 +/- 2.4 MUm; P < 0.001).
      This is the first study to directly compare OCTA against histology from the same
      human eye. OCTA visualizes many of the vascular structures in the human retinal
      circulation but does not exactly match what is seen on histologic examination.

PMID- 29448043
TI  - Estrogen serum concentration affects blood immune cell composition and
      polarization in human females under controlled ovarian stimulation.
AB  - Estrogens modulate the immune system and possess anti-inflammatory properties. In
      line, immune cells express a variety of estrogen receptors (ER) including ER
      alpha and -beta. In the present study, we examined the influence of 17beta
      estradiol (E2) serum concentrations on blood leukocyte composition and their ex
      vivo polarization/activation status by FACS analysis in sub-fertile human females
      under controlled ovarian stimulation (COS). Using a set of cell-type and
      polarization-specific markers, we demonstrate that increased 17beta-estradiol
      (E2) serum concentrations yield an overall increase in leukocytes, neutrophils
      and monocytes but decreased lymphocytes. There was a clear ratio shift towards an
      increase in M2 monocytes with a protective quality and an increase in T-helper
      cells compared to a decrease in cytotoxic T-cells. These data support
      experimental findings and clinical trials, i.e. related to multiple sclerosis and
      other autoimmune-related diseases, that have shown a down-regulation of CD8(+) T
      cells and up-regulation of T-regulatory cells. Further studies have to pinpoint
      to which extent the immune system/-responsiveness of otherwise healthy female
      patients is affected by medium-term systemic E2 variations.

PMID- 29448044
TI  - Safety evaluation of a human chimeric monoclonal antibody that recognizes the
      extracellular loop domain of claudin-2.
AB  - Claudin-2 (CLDN-2), a pore-forming tight junction protein with a tetra
      transmembrane domain, is involved in carcinogenesis and the metastasis of some
      cancers. Although CLDN-2 is highly expressed in the tight junctions of the liver
      and kidney, whether CLDN-2 is a safe target for cancer therapy remains unknown.
      We recently generated a rat monoclonal antibody (mAb, clone 1A2) that recognizes
      the extracellular domains of human and mouse CLDN-2. Here, we investigated the
      safety of CLDN-2-targeted cancer therapy by using 1A2 as a model therapeutic
      antibody. Because most human therapeutic mAbs are IgG1 subtype that can induce
      antibody-dependent cellular cytotoxicity, we generated a human-rat chimeric IgG1
      form of 1A2 (xi-1A2). xi-1A2 activated Fcgamma receptor IIIa in the presence of
      CLDN-2-expressing cells, indicating that xi-1A2 likely exerts antibody-dependent
      cellular cytotoxicity. At 24 h after its intravenous injection, xi-1A2 was
      distributed into the liver, kidney, and tumor tissues of mice bearing CLDN-2
      expressing fibrosarcoma cells. Treatment of the xenografted mice with xi-1A2
      attenuated tumor growth without apparent adverse effects, such as changes in body
      weight and biochemical markers of liver and kidney injury. These results support
      xi-1A2 as the lead candidate mAb for safe CLDN-2-targeted cancer therapy.

PMID- 29448046
TI  - Diurnal variation in admission troponin concentrations in patients with chest
      pain in the emergency department.
AB  - BACKGROUND: Recent studies have suggested that there may be large diurnal
      variation in cardiac troponin T (cTnT) concentrations measured with a high
      sensitive assay. OBJECTIVE: To investigate if clinically relevant diurnal
      variation in cTnT concentrations is present in patients with chest pain in the
      emergency department (ED). METHODS: We included all patients with chest pain, but
      no myocardial infarction (MI), and no other acute condition that may affect
      troponin concentrations in the ED at Karolinska University Hospital, Stockholm,
      Sweden, 2011-2014. Time periods for blood sampling were: 00.00-03.59 am, 04.00
      07.59 am, 08.00-11.59 am, 00.00-03.59 pm, 04.00-07.59 pm, and 08.00-11.59 pm.
      Negative binomial regression models were used to calculate least-square means of
      admission cTnT concentrations with 95% confidence intervals (CIs). RESULTS: A
      total of 19,460 patients were included with a mean age of 54 +/- 16 years.
      Patients who arrived during the night were younger, but other characteristics
      were similar among the time periods. The greatest mean admission cTnT
      concentrations for men (9.0 ng/l, 95% CI, 8.7-9.3), and women (8.0 ng/l, 95% CI,
      7.8-8.2) were found at 08.00-11.59 am. After adjustment for age and estimated
      glomerular filtration rate, no significant diurnal variation in admission cTnT
      concentrations was observed. CONCLUSIONS: In a cohort of unselected patients with
      chest pain, and no acute condition affecting troponin admission concentrations,
      we found no evidence of clinically relevant diurnal variation in admission cTnT
      concentrations. There is no need to take the time point when blood is drawn into
      account in the assessment of admission cTnT concentrations in the ED.

PMID- 29448047
TI  - Genital lubrication: A cue-specific sexual response?
AB  - Women's genital responses are sensitive to the presence and intensity of sexual
      cues, yet some stimulus features (e.g., male vs. female actors, consensual vs.
      non-consensual interactions) have little influence on the magnitude of response-a
      phenomenon called low cue-specificity. Genital responses are typically assessed
      using vaginal photoplethysmography, a measure of vaginal vasocongestion, itself a
      precursor to lubrication. One explanation for low cue-specificity is the
      preparation hypothesis: Women genitally respond to almost all sexual cues because
      lubrication functions to protect genital organs from potential injury should
      vaginal penetration occur. In order to test the preparation hypothesis, both
      vaginal vasocongestion and introital lubrication were assessed in a sample of 20
      women in response to sexually explicit films. While patterns of vasocongestion
      were consistent with low cue-specificity for gender cues and type of sexual
      activity, lubrication was specific to women's most preferred sexual stimulus
      categories. These results are inconsistent with the preparation hypothesis.

PMID- 29448045
TI  - Serum ARCHITECT PIVKA-II reference interval in healthy Chinese adults: Sub
      analysis from a prospective multicenter study.
AB  - BACKGROUND: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) has
      been widely used as a biomarker for liver cancer diagnosis in Japan for decades.
      However, the reference intervals for serum ARCHITECT PIVKA-II have not been
      established in the Chinese population. Thus, this study aimed to measure serum
      PIVKA-II levels in healthy Chinese subjects. METHODS: This is a sub-analysis from
      the prospective, cross-sectional and multicenter study (ClinicalTrials.gov
      Identifier: NCT03047603). A total of 892 healthy participants (777 Han and 115
      Uygur) with complete health checkup results were recruited from 7 regional
      centers in China. Serum PIVKA-II level was measured by ARCHITECT immunoassay. All
      95% reference ranges were estimated by nonparametric method. RESULTS: The
      distribution of PIVKA-II values showed significant difference with ethnicity and
      sex, but not age. The 95% reference range of PIVKA-II was 13.62-40.38 mAU/ml in
      Han Chinese subjects and 15.16-53.74 mAU/ml in Uygur subjects. PIVKA-II level was
      significantly higher in males than in females (P < 0.001). The 95% reference
      range of PIVKA-II was 15.39-42.01 mAU/ml in Han males while 11.96-39.13 mAU/ml in
      Han females. CONCLUSIONS: The reference interval of serum PIVKA-II on the
      Architect platform was established in healthy Chinese adults. This will be
      valuable for future clinical and laboratory studies performed using the Architect
      analyzer. Different ethnic backgrounds and analytical methods underline the need
      for redefining the reference interval of analytes such as PIVKA-II, in central
      laboratories in different countries.

PMID- 29448048
TI  - Scholarly Activity Training During Residency: Are We Hitting the Mark? A National
      Assessment of Pediatric Residents.
AB  - OBJECTIVE: Participation in scholarly activity (SA) is an Accreditation Council
      for Graduate Medical Education requirement. Our previous research with program
      directors (PDs) suggests that pediatric SA training is variable and suboptimal.
      To help programs better meet requirements, our objective was to understand the
      resident perspective regarding SA training, including factors associated with
      satisfaction and productivity. METHODS: We conducted cross-sectional surveys of
      second- and third-year pediatric residents and PDs at 22 diverse programs in
      2016. Surveys assessed resident demographics, career intentions, program
      characteristics, beliefs, barriers, satisfaction, and productivity, defined as SA
      accepted at a regional or national meeting, for publication, or grant funding.
      Data were analyzed using descriptive statistics and multivariable logistic
      regression. RESULTS: A total of 464 (60.2%) of 771 residents and 22 PDs (100%)
      responded. Most residents believed that residents should participate in SA (n =
      380, 81.9%). However, only 37.9% (n = 175) were extremely or very satisfied with
      their training. Residents who reported that training to conduct research
      (adjusted odds ratio [AOR]  = 1.9, 95% confidence interval [CI] 1.1-3.5),
      availability of a research curriculum (AOR = 1.9, 95% CI 1.2-3.1), and adequate
      faculty mentorship (AOR = 2.5, 95% CI 1.6-4.1) were not barriers were more
      satisfied. Protected time was associated with satisfaction (AOR = 1.7, 95% CI 1.1
      2.7). A total of 43.8% of residents (n = 203) were productive. Productivity was
      associated with future plans to conduct research (AOR = 3.3, 95% CI 2.1-5.1).
      CONCLUSIONS: Residents believe SA training is important. Dedicated program
      infrastructure, protected time, and adequate mentorship appear to be crucial to
      improving quality perceptions.

PMID- 29448049
TI  - Gaining Perspectives on Patient and Family Disease Experiences by Storytelling.

PMID- 29448050
TI  - Antimicrobial surfaces to prevent healthcare-associated infections: a systematic
      review - a different view.

PMID- 29448051
TI  - Elasticity and wave velocity in fcc iron (austenite) at elevated temperatures -
      Experimental verification of ab-initio calculations.
AB  - High temperature crystal elasticity constants for face centred cubic austenite
      are important for interpreting the ultrasonic properties of iron and steels but
      cannot be determined by normal single crystal methods. Values of these constants
      have recently been calculated using an ab-initio approach and the present work
      was carried out to test their applicability using laser-ultrasonic measurements.
      Steel samples having a known texture were examined at temperatures between 800 
      degrees C and 1100  degrees C to measure the velocity of longitudinal P-waves
      which were found to be in good agreement with modelled values.

PMID- 29448052
TI  - KIR and HLA ligands demonstrate genetic inheritance diversity in Japanese
      descendants from Parana, Brazil.
AB  - In order to investigate killer immunoglobulin-like receptors (KIR) and their
      ligands, human leukocyte antigen (HLA), diversity in the Brazilian population
      influenced by migrations, unrelated Brazilian Japanese descendants were selected
      and genotyped for the KIR genes and HLA class I allele groups. Genetic
      heterogeneity in Brazil Parana Japanese was observed for KIR genes, whose
      frequency distributions demonstrated similarity with mixed Brazilian populations
      and with the Japanese population, suggesting gene flow. The data contributed to
      the identification of the genetic constitution of the Brazilian population
      influenced by immigrations and two new genotypes were defined.

PMID- 29448053
TI  - Biomarkers of operational tolerance following kidney transplantation - The immune
      tolerance network studies of spontaneously tolerant kidney transplant recipients.
AB  - Studies of kidney transplant recipients who have developed spontaneous and
      sustained tolerance have revealed an association with B cells. Unexpectedly
      tolerant individuals are characterized by increased numbers and frequencies of B
      cells in the blood and increased expression of genes associated with B cells in
      the blood and urine. Comparisons of the B cell repertoires of tolerant
      individuals and those receiving immunosuppression reveal that not only are the B
      cells more numerous but developmental differences result in a repertoire
      comprised of more naive and transitional B cells in the tolerant cohort. B cells
      isolated from tolerant individuals also display functional differences compared
      to those from individuals receiving immunosuppression. Many of these differences
      may serve to suppress alloimmunity. Lastly a significant number of transplant
      recipients receiving standard immunosuppression display B cell-biased patterns of
      gene expression predictive of tolerance or a pro-tolerogenic state.
      Interestingly, this pattern is associated with improved renal allograft function.
      While recent studies have raised the concern that immunosuppressive drugs heavily
      influence B cell-based "signatures of tolerance", a substantial body of work
      suggests that differences in B cells may be a useful tool for identifying
      tolerant kidney transplant recipients or guiding their immunosuppressive
      management.

PMID- 29448054
TI  - RAGE-induced changes in the proteome of alveolar epithelial cells.
AB  - : The receptor for advanced glycation end-products (RAGE) is a pattern
      recognition receptor and member of the immunoglobulin superfamily. RAGE is
      constitutively expressed in the distal lung where it co-localizes with the
      alveolar epithelium; RAGE expression is otherwise minimal or absent, except with
      disease. This suggests RAGE plays a role in lung physiology and pathology. We
      used proteomics to identify and characterize the effects of RAGE on rat alveolar
      epithelial (R3/1) cells. LC-MS/MS identified 177 differentially expressed
      proteins and the PANTHER Classification System further segregated proteins.
      Proteins involved in gene transcription (RNA and mRNA splicing, mRNA processing)
      and transport (protein, intracellular protein) were overrepresented; genes
      involved in a response to stimulus were underrepresented. Immune system processes
      and response to stimuli were downregulated with RAGE knockdown. Western blot
      confirmed RAGE-dependent changes in protein expression for NFkappaB and NLRP3
      that was functionally supported by a reduction in IL-1beta and phosphorylated
      p65. We also assessed RAGE's effect on redox regulation and report that RAGE
      knockdown attenuated oxidant production, decreased protein oxidation, and
      increased reduced thiol pools. Collectively the data suggest that RAGE is a
      critical regulator of epithelial cell response and has implications for our
      understanding of lung disease, specifically acute lung injury. SIGNIFICANCE
      STATEMENT: In the present study, we undertook the first proteomic evaluation of
      RAGE-dependent processes in alveolar epithelial cells. The alveolar epithelium is
      a primary target during acute lung injury, and our data support a role for RAGE
      in gene transcription, protein transport, and response to stimuli. More over our
      data suggest that RAGE is a critical driver of redox regulation in the alveolar
      epithelium. The conclusions of the present work assist to unravel the molecular
      events that underlie the function of RAGE in alveolar epithelial cells and have
      implications for our understanding of RAGE signaling during lung injury. Our
      study was the first proteomic comparison showing the effects of RAGE activation
      from alveolar epithelial cells that constitutively express RAGE and these results
      can affect a wide field of lung biology, pulmonary therapeutics, and proteomics.

PMID- 29448055
TI  - Proteomic characterization of Withaferin A-targeted protein networks for the
      treatment of monoclonal myeloma gammopathies.
AB  - : Withaferin A (WA), a natural steroid lactone from the plant Withania somnifera,
      is often studied because of its antitumor properties. Although many in vitro and
      in vivo studies have been performed, the identification of Withaferin A protein
      targets and its mechanism of antitumor action remain incomplete. We used
      quantitative chemoproteomics and differential protein expression analysis to
      characterize the WA antitumor effects on a multiple myeloma cell model.
      Identified relevant targets were further validated by Ingenuity Pathway Analysis
      and Western blot and indicate that WA targets protein networks that are specific
      for monoclonal gammopathy of undetermined significance (MGUS) and other closely
      related disorders, such as multiple myeloma (MM) and Waldenstrom
      macroglobulinemia (WM). By blocking the PSMB10 proteasome subunit, downregulation
      of ANXA4, potential association with HDAC6 and upregulation of HMOX1, WA puts a
      massive blockage on both proteotoxic and oxidative stress responses pathways,
      leaving cancer cells defenseless against WA induced stresses. These results
      indicate that WA mediated apoptosis is preceded by simultaneous targeting of
      cellular stress response pathways like proteasome degradation, autophagy and
      unfolded protein stress response and thus suggests that WA can be used as an
      effective treatment for MGUS and other closely related disorders. SIGNIFICANCE:
      Multifunctional antitumor compounds are of great potential since they reduce the
      risk of multidrug resistance in chemotherapy. Unfortunately, characterization of
      all protein targets of a multifunctional compound is lacking. Therefore, we
      optimized an SILAC quantitative chemoproteomics workflow to identify the
      potential protein targets of Withaferin A (WA), a natural multifunctional
      compound with promising antitumor properties. To further understand the antitumor
      mechanisms of WA, we performed a differential protein expression analysis and
      combined the altered expression data with chemoproteome WA target data in the
      highly curated Ingenuity Pathway database. We provide a first global overview on
      how WA kills multiple myeloma cancer cells and serve as a starting point for
      further in depth experiments. Furthermore, the combined approach can be used for
      other types of cancer and/or other promising multifunctional compounds, thereby
      increasing the potential development of new antitumor therapies.

PMID- 29448056
TI  - Proteomic analysis of first trimester maternal serum to identify candidate
      biomarkers potentially predictive of spontaneous preterm birth.
AB  - : Spontaneous preterm birth (sPTB) remains a major clinical dilemma; current
      diagnostics and interventions have not reduced the rate of this serious
      healthcare burden. This study characterizes differential protein profiles and
      post-translational modifications (PTMs) in first trimester maternal serum using a
      refined top-down approach coupling two-dimensional gel electrophoresis (2DE) and
      mass spectrometry (MS) to directly compare subsequent term and preterm labour
      events and identify marked protein differences. 30 proteoforms were found to be
      significantly increased or decreased in the sPTB group including 9
      phosphoproteins and 11 glycoproteins. Changes occurred in proteins associated
      with immune and defence responses. We identified protein species that are
      associated with several clinically relevant biological processes, including
      interrelated biological networks linked to regulation of the complement cascade
      and coagulation pathways, immune modulation, metabolic processes and cell
      signalling. The finding of altered proteoforms in maternal serum from pregnancies
      that delivered preterm suggests these as potential early biomarkers of sPTB and
      also possible mediators of the disorder. BIOLOGICAL SIGNIFICANCE: Identifying
      changes in protein profiles is critical in the study of cell biology, and disease
      treatment and prevention. Identifying consistent changes in the maternal serum
      proteome during early pregnancy, including specific protein PTMs (e.g.
      phosphorylation, glycosylation), is likely to provide better opportunities for
      prediction, intervention and prevention of preterm birth. This is the first study
      to examine first trimester maternal serum using a highly refined top-down
      proteomic analytical approach based on high resolution 2DE coupled with mass
      spectrometry to directly compare preterm (<37 weeks) and preterm (>=37 weeks)
      events and identify select protein differences between these conditions. As such,
      the data present a promising avenue for translation of biomarker discovery to a
      clinical setting as well as for future investigation of underlying aetiological
      processes.

PMID- 29448057
TI  - HLA-Matched Sibling versus Unrelated versus Haploidentical Related Donor
      Allogeneic Hematopoietic Stem Cell Transplantation for Patients Aged Over 60
      Years with Acute Myeloid Leukemia: A Single-Center Donor Comparison.
AB  - Haploidentical related donor (HRD) allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) was developed as a valid option for the treatment of
      acute myeloid leukemia (AML) in the absence of a matched donor. However, many
      investigators are reluctant to consider the use of this alternative in elderly
      patients, anticipating high morbidity. Here, we report a single-center comparison
      of HRD versus matched sibling donor (MSD) and unrelated donor (UD) allo-HSCT for
      patients with AML aged >=60 years. Ninety-four patients (MSD: n = 31; UD: n = 30;
      HRD: n = 33) were analyzed. The median age was 65 (range, 60 to 73) years. We
      observed a higher cumulative incidence of grade 3 to 4 acute graft-versus-host
      disease (GVHD) after UD allo-HSCT (MSD versus UD versus HRD: 3% versus 33% versus
      6%, respectively; P = .006). Two-year cumulative incidence of moderate or severe
      chronic GVHD was 17%, 27%, and 16% in the MSD, UD, and HRD groups, respectively
      (P = .487). No difference was observed in the 2-year cumulative incidence of
      relapse or nonrelapse mortality (NRM) (relapse: MSD versus UD versus HRD: 32%
      versus 25% versus 25%, respectively; P = .411; NRM: MSD versus UD versus HRD: 19%
      versus 27% versus 24%, respectively; P = .709). At 2 years, progression-free
      survival, overall survival, and GVHD- and relapse-free survival were 48%, 50%,
      and 39%, respectively, in the MSD group; 48%, 51%, and 23%, respectively, in the
      UD group; and 50%, 52%, and 32%, respectively, in the HRD group, without
      statistically significant differences between the groups. We conclude that HRD
      allo-HSCT is highly feasible and no less efficient than MSD or UD allo-HSCT in
      patients with AML aged >=60 years. Thus, the absence of a HLA-identical donor
      should not limit the consideration of allo-HSCT for the treatment of AML.

PMID- 29448058
TI  - Early Post-Transplant Minimal Residual Disease Assessment Improves Risk
      Stratification in Acute Myeloid Leukemia.
AB  - We studied if the inclusion of early post-stem cell transplantation (SCT) minimal
      residual disease (MRD) assessments improved prognostication in patients with
      acute myeloid leukemia (AML). Two hundred sixty-nine AML patients in
      morphological complete remission (CR) who underwent a first SCT were included if
      they had evaluable pre-SCT MRD assessment by multiparametric flow cytometry. Post
      SCT MRD assessments were performed at days +30, +100, and +180. The primary
      outcome was 1-year relapse incidence (RI). Of 269 patients in CR, 83 (30.8%) had
      detectable MRD pre-SCT. Post-SCT, during routine disease assessment time points,
      9 of 241 evaluable patients (3.7%) at day +30, 6 of 191 evaluable patients (3.1%)
      at day +100, and 4 of 133 evaluable patients (3%) at day +180 were MRD positive
      while in CR. MRD positivity at day +30 predicted the highest risk of relapse at 1
      year (group 1, 1-year RI 78%). Among MRD-negative patients at day +30, either
      adverse risk category by European Leukemia Net (ELN) or intermediate risk who
      were aged >=60 years and/or pre-SCT MRD-positive represented the intermediate
      risk group (group 2, 1-year RI 29%). The remaining patients represented the low
      risk group (group 3, 1-year RI 5%). For patients in CR beyond day +30 post-SCT,
      detectable MRD at any time point predicted impending relapse within 2 months.
      Early post-SCT MRD assessment-combined with pre-SCT MRD assessment, ELN risk
      category, and age-improves risk stratification for relapse in AML patients post
      transplant. Studies aimed at preventing impending relapse in this high-risk
      population are urgently needed.

PMID- 29448059
TI  - Monte Carlo simulation of the relative biological effectiveness and DNA damage
      from a 400 MeV/u carbon ion beam in water.
AB  - A 400 MeV/u carbon ion beam incident on a water phantom was simulated with
      GATE/Geant4 to calculate the energy spectra of 12C and its fragments at various
      depths. Based on the energy spectra, the DNA double strand break (DSB) yields
      from 12C and its fragments were calculated with Monte Carlo Damage Simulation
      (MCDS) code. The relative biological effectiveness (RBE) distributions for 12C
      and its fragments were calculated from the DSB yields. The DNA damages from each
      type of the particles and their contribution to the total DNA damages at various
      depths were calculated from the DSB yields and dose distributions. These
      characteristics of 12C and its fragments are important for understanding the
      corresponding RBEs and the DNA damages. The purpose of this work was to obtain
      the RBEs and the DNA damage distributions of carbon ions and their fragments in
      beams used in radiotherapy by means of simulating the macroscopic phantom and
      microscopic cells. The simulation method can be easily extended by changing some
      parameters.

PMID- 29448060
TI  - A rapid method for the sequential separation of polonium, plutonium, americium
      and uranium in drinking water.
AB  - A new sequential separation method for the determination of polonium and
      actinides (Pu, Am and U) in drinking water samples has been developed that can be
      used for emergency response or routine water analyses. For the first time, the
      application of TEVA chromatography column in the sequential separation of
      polonium and plutonium has been studied. This method utilizes a rapid Fe+3 co
      precipitation step to remove matrix interferences, followed by plutonium
      oxidation state adjustment to Pu4+ and an incubation period of ~ 1 h at 50-60 
      degrees C to allow Po2+ to oxidize to Po4+. The polonium and plutonium were then
      separated on a TEVA column, while separation of americium from uranium was
      performed on a TRU column. After separation, polonium was micro-precipitated with
      copper sulfide (CuS), while actinides were micro co-precipitated using neodymium
      fluoride (NdF3) for counting by the alpha spectrometry. The method is simple,
      robust and can be performed quickly with excellent removal of interferences, high
      chemical recovery and very good alpha peak resolution. The efficiency and
      reliability of the procedures were tested by using spiked samples. The effect of
      several transition metals (Cu2+, Pb2+, Fe3+, Fe2+, and Ni2+) on the performance
      of this method were also assessed to evaluate the potential matrix effects.
      Studies indicate that presence of up to 25 mg of these cations in the samples had
      no adverse effect on the recovery or the resolution of polonium alpha peaks.

PMID- 29448061
TI  - Allocation rules for global donors.
AB  - In recent years, donors such as the Bill and Melinda Gates Foundation have made
      an enormous contribution to the reduction of the global burden of disease. It has
      been argued that such donors should prioritise interventions based on their cost
      effectiveness, that is to say, the ratio of costs to benefits. Against this, we
      argue that the donor should fund not the most cost-effective interventions, but
      rather interventions which are just cost-ineffective for the country, thus
      encouraging the country to contribute its own domestic resources to the fight
      against disease. We demonstrate that our proposed algorithm can be justified
      within the context of a model of the problem as a leader-follower game, in which
      a donor chooses to subsidise interventions which are implemented by a country. We
      argue that the decision rule we propose provides a basis for the allocation of
      aid money which is efficient, fair and sustainable.

PMID- 29448062
TI  - Geological data indicate that the interpretation for the age-calibrated phylogeny
      for the Kurixalus-genus frogs of South, South-east and East Asia (Lv et al.,
      2018) needs to be rethought.
AB  - Recently, Lv et al. (2018) published an age-calibrated phylogenetic tree for the
      Kurixalus frogs, members of which occur across parts of South, South-east and
      East Asia. A clade on Taiwan, represented by Kurixalus idiootocus and the
      Kurixalus eiffingeri species complex, is deemed to have been resident since the
      middle Cenozoic; its closest congeners are in southern Indochina (not in the
      adjacent parts of south-east China), and the split between the two is dated at
      32.8 Ma. Furthermore, a sub-population of Kurixalus eiffingeri is believed to
      have colonized islands in the western Ryukyus c. 13.5 Ma. There is, however, a
      problem with this scenario: the landmass regarded as modern-day Taiwan has
      existed only for 4-5 million years (it results from a young and ongoing tectonic
      plate collision). Assuming the Kurixalus phylogeny and the dating of its
      branchings are correct, then a palaeobiogeographical scenario involving an older,
      alternative land surface with later transfer to Taiwan, possibly involving over
      water dispersal, would reconcile the biology, but testing this may be
      difficult/impossible. If the ages of the nodes in the proposed tree are found to
      be significantly overestimated, the geology and biology might more easily be
      accommodated.

PMID- 29448063
TI  - An ant genus-group (Prenolepis) illuminates the biogeography and drivers of
      insect diversification in the Indo-Pacific.
AB  - The Malay Archipelago and the tropical South Pacific (hereafter the Indo-Pacific
      region) are considered biodiversity hotspots, yet a general understanding of the
      origins and diversification of species-rich groups in the region remains elusive.
      We aimed to test hypotheses for the evolutionary processes driving insect species
      diversity in the Indo-Pacific using a higher-level and comprehensive phylogenetic
      hypothesis for an ant clade consisting of seven genera. We estimated divergence
      times and reconstructed the biogeographical history of ant species in the
      Prenolepis genus-group (Formicidae: Formicinae: Lasiini). We used a fossil
      calibrated phylogeny to infer ancestral geographical ranges utilizing a
      biogeographic model that includes founder-event speciation. Ancestral state
      reconstructions of the ants' ecological preferences, and diversification rates
      were estimated for selected Indo-Pacific clades. Overall, we report that faunal
      interchange between Asia and Australia has occurred since at least 20-25 Ma, and
      early dispersal to the Fijian Basin happened during the early and mid-Miocene
      (ca. 10-20 Ma). Differences in diversification rates across Indo-Pacific clades
      may be related to ecological preference breadth, which in turn may have
      facilitated geographical range expansions. Ancient dispersal routes suggested by
      our results agree with the palaeogeography of the region. For this particular
      group of ants, the rapid orogenesis in New Guinea and possibly subsequent
      ecological shifts may have promoted their rapid diversification and widespread
      distribution across the Indo-Pacific.

PMID- 29448064
TI  - Toxicity of different fatty acids and methyl esters on Culex quinquefasciatus
      larvae.
AB  - The Culex quinquefasciatus mosquito is a vector of several diseases, and its
      control has been performed with synthetic insecticides, which may have human and
      environmental side effects. Thus, the use of new and safe molecules are
      important, and this study evaluated the toxicity of active substances against
      this mosquito. The oleic, linoleic, linolenic, palmitic and stearic acids and
      their respective methyl esters were tested against fourth instar C.
      quinquefasciatus larvae. Oleic, linoleic and linolenic acids had LC50 values of
      8.58, 10.04 and 19.78 mg/L, respectively. Histological analysis showed that these
      three compounds caused cell instability with an increase in the number of
      vesicles in the fat body and in the midgut cells. Based on these results,
      glucose, triglyceride, and protein levels were evaluated after 1 h of acid
      exposure. These compounds decreased in insects treated with linoleic acid.
      Linolenic acid also caused a significant increase in acetylcholinesterase
      activity. These results show that oleic, linoleic, and linoleic acids have a
      lower LC50 for C. quinquefasciatus, affecting its metabolism and the morphology
      of midgut and fat body.

PMID- 29448065
TI  - Impact of non-apnea sleep disorders on diabetic control and metabolic outcome - A
      population-based cohort study.
AB  - OBJECTIVE: There has been a growing recognition that obstructive sleep apnea
      (OSA) could increase the propensity for type 2 diabetes the metabolic syndrome.
      However, studies concerning about the impact of non-apnea sleep disorders (NSD)
      on diabetes control and metabolic outcomes are relatively scarce. Our aim is to
      investigate the impact of non-apnea sleep disorders (NSD) on diabetic control and
      associated metabolic outcomes in patients with type 2 diabetes. METHODS: The data
      were obtained from two nationwide population-based databases for a period 2007 to
      2012. A total 66,992 patients with type 2 diabetes were enrolled and divided into
      two cohorts based on comorbidity with or without a NSD diagnosis, and were
      followed up four years. The primary outcomes were to compare rate of change in
      HbA1c and associated metabolic outcomes during follow-up visits between patients
      with or without NSD. The secondary outcome is to examine whether NSD were
      associated with poor glycemic control of the last clinical records while
      controlling for the baseline HbA1c value. RESULTS: Of the 66,992 patients with
      type 2 diabetes, 14.82% had comorbidity with a NSD. HbA1C decreases were
      significantly lower by 0.04% in the NSD group (P < 0.05), and triglyceride (TG)
      decreases remained significantly lower by 2.53% in the NSD group (P < 0.05).
      Furthermore, patients in the NSD group had an 8% higher risk of poor glycemic
      control (HbA1C >9) (OR = 1.08; 95%CI, 1.01-1.16). CONCLUSION: Our findings
      indicated patients with type 2 diabetes comorbid with NSD had a slower
      improvement in HbA1c compared with the comparison cohort. It may because there
      may exist potential floor effect given those with NSD having significantly lower
      HbA1c values at baseline. On the other hand, the poor diabetic control among
      those with NSD may be also affected by other confounders such as medical
      treatment or interventions. Nevertheless, given the rapidly increasing prevalence
      of metabolic diseases and subsequent complications, the results may highlight the
      importance of sleep in the clinical management of type 2 diabetes.

PMID- 29448066
TI  - Single step purification via magnetic nanoparticles of new broad pH active
      protease from Penicillium aurantiogriseum.
AB  - A new set of applications can be achieved when using high stability proteases.
      Industrially, high costs can be related to production medium and purification
      process. Magnetic nanoparticles have been successfully used for rapid and
      scalable purification. In this work, azocasein were immobilized on magnetite
      nanoparticles and applied in a single step purification of protease produced by
      Penicillium aurantiogriseum using soybean flour medium, and the new purified
      enzyme was characterized. Glutaraldehyde activated nanoparticles were used in
      azocasein immobilization and then incubated with dialyzed 60-80% saline
      precipitation fraction of crude extract for purification. Adsorbents were washed
      7 times (0.1 M NaCl solution) and eluted 3 times (1 M NaCl solution), these final
      elutions contained the purified protease. This protease was purified 55.68-fold,
      retaining 46% of its original activity. Presented approximately 40 kDa on SDS
      PAGE and optimum activity at 45  degrees C and pH 9.0. Maintained over 60% of
      activity from pH 6.0 to 11.0. Kept more than 50% activity from 15 to 55  degrees
      C, did not lose any activity over 48 h at 25  degrees C. Inhibitors assay
      suggested a serine protease with aspartic residues on its active site. Results
      report a successful application of an alternative purification method and novel
      broad pH tolerant protease.

PMID- 29448067
TI  - Antiviral resistance due to deletion in the neuraminidase gene and defective
      interfering-like viral polymerase basic 2 RNA of influenza A virus subtype H3N2.
AB  - BACKGROUND AND OBJECTIVE: Antiviral treatment of influenza virus infections can
      lead to drug resistance of virus. This study investigates a selection of
      mutations in the full genome of H3N2 influenza A virus isolated from a patient in
      treatment with oseltamivir. STUDY DESIGN: Respiratory samples from a patient were
      collected before, during, and after antiviral treatment. Whole genome sequencing
      of the influenza virus by next generation sequencing, and low-frequency-variant
      analysis was performed. Neuraminidase-inhibition tests were performed with
      oseltamivir and zanamivir, and viruses were propagated in sial-transferase gene
      transfected Madin-Darby Canine Kidney cells. RESULTS: A deletion at amino acid
      position 245-248 in the neuraminidase gene occurred after initiation of treatment
      with oseltamivir. The deleted virus had highly reduced inhibition against
      oseltamivir but was sensitive to zanamivir. Nine days after discontinuation of
      oseltamivir treatment the deleted H3N2 virus was still present in the patient.
      After three passages of the deleted virus in cell culture, the deletion was
      retained. Several variant mutations appeared in the other genes of the H3N2
      virus, where most striking were two major out-of-frame deletions in the
      polymerase basic 2 (PB2) gene, indicating defective interfering-like viral RNA.
      CONCLUSIONS: The viruses harboring the 245-248 deletion in the neuraminidase gene
      were still present after discontinuation of oseltamivir treatment and passages in
      cell cultures, indicating a potential risk for transmission of the deleted virus.
      Full genome deep sequencing was useful to reveal variant mutations that might be
      selected due to antiviral treatment, and defective interfering-like viral PB2 RNA
      in the respiratory samples was detected.

PMID- 29448068
TI  - Systems immunology allows a new view on human dendritic cells.
AB  - As the most important antigen-presenting cells, dendritic cells connect the
      innate and adaptive part of our immune system and play a pivotal role in our
      course of action against invading pathogens as well as during successful
      vaccination. Immunologists have therefore studied these cells in great detail
      using flow cytometry-based analyses, in vitro assays and in vivo models, both in
      murine models and in humans. Albeit, sophisticated, classical immunological, and
      molecular approaches were often unable to unequivocally determine the
      subpopulation structure of the dendritic cell lineage and not surprisingly,
      conflicting results about dendritic cell subsets co-existed throughout the last
      decades. With the advent of systems approaches and the most recent introduction
      of -omics approaches on the single cell level combined with multi-colour flow
      cytometry or mass cytometry, we now enter an era allowing us to define cell
      population structures with an unprecedented precision. We will report here on the
      most recent studies applying these technologies to human dendritic cells. Proper
      delineation of and definition of molecular signatures for the different human
      dendritic cell subsets will greatly facilitate studying these cells in the
      future: understanding their function under physiological as well as pathological
      conditions.

PMID- 29448069
TI  - Micro-environmental signals directing human epidermal Langerhans cell
      differentiation.
AB  - Human Langerhans cells (LC) can be generated ex vivo from hematopoietic precursor
      cells in response to cytokines and cell-membrane associated ligands. These in
      vitro differentiation models provided mechanistic insights into the molecular and
      cellular pathways underlying the development of this unique, epithelia-associated
      dendritic cell subset. Notably, the human epidermal microenvironment is fully
      sufficient to induce LC differentiation from hematopoietic progenitors. Hence,
      dissecting the molecular characteristics of the human epithelial/epidermal LC
      niche, and testing defined ligands for their capacity to induce LC
      differentiation, led to a refined molecular model of LC lineage commitment.
      During epidermal ontogeny, spatially and temporally regulated availability of TGF
      beta family members cooperate with other keratinocyte-derived signals, such as E
      cadherin and Notch ligands, for instructing LC differentiation. In this review,
      we discuss the signals known to instruct human hematopoietic progenitor cells and
      myelomonocytic cells to undergo LC lineage commitment. Additionally, the current
      methods for generation of large numbers of human LC-like cells ex vivo in defined
      serum-free media are discussed.

PMID- 29448070
TI  - Human in vivo-differentiated monocyte-derived dendritic cells.
AB  - When entering tissues, monocytes can differentiate into cells that share
      morphological and functional features with either dendritic cells (DC) or
      macrophages. Monocyte-derived DC have been observed in humans at mucosal tissues
      and in inflammatory settings, where they are usually referred to as "inflammatory
      DC". In this chapter, we review recent studies on the characterization of these
      cells in humans. We also discuss nomenclature and examine the criteria defining
      in vivo-differentiated human mo-DC.

PMID- 29448071
TI  - Activating embryonic development in Drosophila.
AB  - The transition from oocyte to embryo marks the onset of development. This process
      requires complex regulation to link developmental signals with profound changes
      in mRNA translation, cell cycle control, and metabolism. This control is
      beginning to be understood for most organisms, and research in the fruit fly
      Drosophila melanogaster has generated new insights. Recent findings have
      increased our understanding of the roles played by hormone and Ca2+ signaling
      events as well as metabolic remodeling crucial for this transition. Specialized
      features of the structure and assembly of the meiotic spindle have been
      identified. The changes in protein levels, mRNA translation, and polyadenylation
      that occur as the oocyte becomes an embryo have been identified together with key
      aspects of their regulation. Here we highlight these important developments and
      the insights they provide on the intricate regulation of this dramatic
      transition.

PMID- 29448072
TI  - A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and
      trastuzumab reference product in HER2-positive early breast cancer treated with
      neoadjuvant-adjuvant treatment: Final safety, immunogenicity and survival
      results.
AB  - BACKGROUND: The equivalent efficacy between SB3, a proposed trastuzumab
      biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast
      pathologic complete response rate after neoadjuvant therapy in patients with
      early or locally advanced human epidermal growth factor receptor 2-positive
      breast cancer was demonstrated in the previous report. Here, we report the final
      safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment.
      PATIENTS AND METHODS: Patients were randomised 1:1 to receive neoadjuvant SB3 or
      TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed
      by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide). Patients then
      underwent surgery, followed by 10 cycles of adjuvant SB3 or TRZ as randomised.
      End-points included safety, immunogenicity, event-free survival (EFS) and overall
      survival through the adjuvant period. RESULTS: Of 875 patients randomised, 764
      (SB3, n = 380; TRZ, n = 384) completed the study. The median follow-up duration
      was 437 days in the SB3 group and 438 days in the TRZ group. The incidence of
      treatment-emergent adverse events was comparable between groups (SB3, 97.5%; TRZ,
      96.1%) during the overall study period. Up to the end of study, the overall
      incidence of antidrug antibody was low in both treatment groups (3 patients
      each). EFS was comparable between groups with a hazard ratio (SB3/TRZ) of 0.94
      (95% confidence interval, 0.59-1.51) and EFS rates at 12 months of 93.7% for SB3
      and 93.4% for TRZ. CONCLUSIONS: Final safety, immunogenicity and survival results
      of this study further support the biosimilarity established between SB3 and TRZ.
      TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149524); EudraCT (2013-004172-35).

PMID- 29448073
TI  - Neurite imaging reveals microstructural variations in human cerebral cortical
      gray matter.
AB  - We present distinct patterns of neurite distribution in the human cerebral cortex
      using diffusion magnetic resonance imaging (MRI). We analyzed both high
      resolution structural (T1w and T2w images) and diffusion MRI data in 505 subjects
      from the Human Connectome Project. Neurite distributions were evaluated using the
      neurite orientation dispersion and density imaging (NODDI) model, optimized for
      gray matter, and mapped onto the cortical surface using a method weighted towards
      the cortical mid-thickness to reduce partial volume effects. The estimated
      neurite density was high in both somatosensory and motor areas, early visual and
      auditory areas, and middle temporal area (MT), showing a strikingly similar
      distribution to myelin maps estimated from the T1w/T2w ratio. The estimated
      neurite orientation dispersion was particularly high in early sensory areas,
      which are known for dense tangential fibers and are classified as granular cortex
      by classical anatomists. Spatial gradients of these cortical neurite properties
      revealed transitions that colocalize with some areal boundaries in a recent multi
      modal parcellation of the human cerebral cortex, providing mutually supportive
      evidence. Our findings indicate that analyzing the cortical gray matter neurite
      morphology using diffusion MRI and NODDI provides valuable information regarding
      cortical microstructure that is related to but complementary to
      myeloarchitecture.

PMID- 29448074
TI  - A probabilistic approach to discovering dynamic full-brain functional
      connectivity patterns.
AB  - Recent research shows that the covariance structure of functional magnetic
      resonance imaging (fMRI) data - commonly described as functional connectivity -
      can change as a function of the participant's cognitive state (for review see
      Turk-Browne, 2013). Here we present a Bayesian hierarchical matrix factorization
      model, termed hierarchical topographic factor analysis (HTFA), for efficiently
      discovering full-brain networks in large multi-subject neuroimaging datasets.
      HTFA approximates each subject's network by first re-representing each brain
      image in terms of the activities of a set of localized nodes, and then computing
      the covariance of the activity time series of these nodes. The number of nodes,
      along with their locations, sizes, and activities (over time) are learned from
      the data. Because the number of nodes is typically substantially smaller than the
      number of fMRI voxels, HTFA can be orders of magnitude more efficient than
      traditional voxel-based functional connectivity approaches. In one case study, we
      show that HTFA recovers the known connectivity patterns underlying a collection
      of synthetic datasets. In a second case study, we illustrate how HTFA may be used
      to discover dynamic full-brain activity and connectivity patterns in real fMRI
      data, collected as participants listened to a story. In a third case study, we
      carried out a similar series of analyses on fMRI data collected as participants
      viewed an episode of a television show. In these latter case studies, we found
      that the HTFA-derived activity and connectivity patterns can be used to reliably
      decode which moments in the story or show the participants were experiencing.
      Further, we found that these two classes of patterns contained partially non
      overlapping information, such that decoders trained on combinations of activity
      based and dynamic connectivity-based features performed better than decoders
      trained on activity or connectivity patterns alone. We replicated this latter
      result with two additional (previously developed) methods for efficiently
      characterizing full-brain activity and connectivity patterns.

PMID- 29448075
TI  - Improving mass-univariate analysis of neuroimaging data by modelling important
      unknown covariates: Application to Epigenome-Wide Association Studies.
AB  - Statistical inference on neuroimaging data is often conducted using a mass
      univariate model, equivalent to fitting a linear model at every voxel with a
      known set of covariates. Due to the large number of linear models, it is
      challenging to check if the selection of covariates is appropriate and to modify
      this selection adequately. The use of standard diagnostics, such as residual
      plotting, is clearly not practical for neuroimaging data. However, the selection
      of covariates is crucial for linear regression to ensure valid statistical
      inference. In particular, the mean model of regression needs to be reasonably
      well specified. Unfortunately, this issue is often overlooked in the field of
      neuroimaging. This study aims to adopt the existing Confounder Adjusted Testing
      and Estimation (CATE) approach and to extend it for use with neuroimaging data.
      We propose a modification of CATE that can yield valid statistical inferences
      using Principal Component Analysis (PCA) estimators instead of Maximum Likelihood
      (ML) estimators. We then propose a non-parametric hypothesis testing procedure
      that can improve upon parametric testing. Monte Carlo simulations show that the
      modification of CATE allows for more accurate modelling of neuroimaging data and
      can in turn yield a better control of False Positive Rate (FPR) and Family-Wise
      Error Rate (FWER). We demonstrate its application to an Epigenome-Wide
      Association Study (EWAS) on neonatal brain imaging and umbilical cord DNA
      methylation data obtained as part of a longitudinal cohort study. Software for
      this CATE study is freely available at
      http://www.bioeng.nus.edu.sg/cfa/Imaging_Genetics2.html.

PMID- 29448076
TI  - Single multi-echo GRE acquisition with short and long echo spacing for
      simultaneous quantitative mapping of fat fraction, B0 inhomogeneity, and
      susceptibility.
AB  - Multi-echo gradient echo (mGRE) sequences have been widely adapted in clinical
      and scientific practice for different purposes to their capability of performing
      Dixon MRI, generating multi-contrast images and extracting multi-parametric maps.
      This work aims to extend mGRE-based techniques for imaging whole head, where
      further technical developments are required due to the co-existence of fat and
      large B0 inhomogeneity in regions such as the skull base and neck. Specifically,
      bipolar mGRE data were acquired with a single sequence that contains both a short
      echo-spacing (DeltaTE) echo train to capture water-fat and B0 phase shifts (for
      proton density fat-fraction (FF) and B0 mapping) and a longer DeltaTE echo train
      (and long echo times) to capture subtle susceptibility variations and R2*
      information. The mGRE images covering the whole head (spatial resolution 1.0 *
      1.0 * 2.0 mm3) were acquired in 5 min. An automated processing pipeline was
      implemented to use the FF and B0 maps determined from the short-TE train to
      compensate for the effects of fat, remove the background phase for whole-head
      quantitative susceptibility mapping, and reduce the difficulty of spatial phase
      unwrapping of the long echo-time data. Data from healthy volunteers imaged on a 3
      T scanner along with phantom validation are presented. Co-registered quantitative
      multi-parametric maps (FF, B0 inhomogeneity, R2*, local frequency shift and
      quantitative susceptibility) and multi-contrast images covering the whole head
      were successfully generated in processing times of several minutes.

PMID- 29448077
TI  - Robust detrending, rereferencing, outlier detection, and inpainting for
      multichannel data.
AB  - Electroencephalography (EEG), magnetoencephalography (MEG) and related techniques
      are prone to glitches, slow drift, steps, etc., that contaminate the data and
      interfere with the analysis and interpretation. These artifacts are usually
      addressed in a preprocessing phase that attempts to remove them or minimize their
      impact. This paper offers a set of useful techniques for this purpose: robust
      detrending, robust rereferencing, outlier detection, data interpolation
      (inpainting), step removal, and filter ringing artifact removal. These techniques
      provide a less wasteful alternative to discarding corrupted trials or channels,
      and they are relatively immune to artifacts that disrupt alternative approaches
      such as filtering. Robust detrending allows slow drifts and common mode signals
      to be factored out while avoiding the deleterious effects of glitches. Robust
      rereferencing reduces the impact of artifacts on the reference. Inpainting allows
      corrupt data to be interpolated from intact parts based on the correlation
      structure estimated over the intact parts. Outlier detection allows the corrupt
      parts to be identified. Step removal fixes the high-amplitude flux jump artifacts
      that are common with some MEG systems. Ringing removal allows the ringing
      response of the antialiasing filter to glitches (steps, pulses) to be suppressed.
      The performance of the methods is illustrated and evaluated using synthetic data
      and data from real EEG and MEG systems. These methods, which are mainly automatic
      and require little tuning, can greatly improve the quality of the data.

PMID- 29448078
TI  - Resin glycosides from the seeds of Ipomoea muricata and their multidrug
      resistance reversal activities.
AB  - Resin glycosides represent an important chemotaxonomic marker of the
      Convolvulaceae family and possess multidrug resistance (MDR) reversal activity.
      In our recent study, nine previously undescribed resin glycosides, Calonyctins B
      J, were isolated from the seeds of Ipomoea muricata. Their structures with the
      absolute configuration were established on the basis of comprehensive
      spectroscopic analysis and chemical methods. Among these, Calonyctins F-I
      possessed a skeleton in which the aglycone moiety and the oligosaccharide core
      were linked by a 3-hydroxy-2-methylbutanoic acid moiety to form a 25-membered
      macrocyclic structure. Calonyctins E, J, and muricatic acid C methyl ester were
      non-cytotoxic but enhanced the cytotoxicity of vincristine by 2.5-407.1 fold at
      25 MUM in KB/VCR cells. Calonyctin E was the most active one.

PMID- 29448079
TI  - Identifying the underlying causes of biological instability in a full-scale
      drinking water supply system.
AB  - Changes in bacterial concentration and composition in drinking water during
      distribution are often attributed to biological (in)stability. Here we assessed
      temporal biological stability in a full-scale distribution network (DN) supplied
      with different types of source water: treated and chlorinated surface water and
      chlorinated groundwater produced at three water treatment plants (WTP).
      Monitoring was performed weekly during 12 months in two locations in the DN. Flow
      cytometric total and intact cell concentration (ICC) measurements showed
      considerable seasonal fluctuations, which were different for two locations. ICC
      varied between 0.1-3.75 * 105 cells mL-1 and 0.69-4.37 * 105 cells mL-1 at two
      locations respectively, with ICC increases attributed to temperature-dependent
      bacterial growth during distribution. Chlorinated water from the different WTP
      was further analysed with a modified growth potential method, identifying primary
      and secondary growth limiting compounds. It was observed that bacterial growth in
      the surface water sample after chlorination was primarily inhibited by phosphorus
      limitation and secondly by organic carbon limitation, while carbon was limiting
      in the chlorinated groundwater samples. However, the ratio of available nutrients
      changed during distribution, and together with disinfection residual decay, this
      resulted in higher bacterial growth potential detected in the DN than at the WTP.
      In this study, bacterial growth was found to be higher (i) at higher water
      temperatures, (ii) in samples with lower chlorine residuals and (iii) in samples
      with less nutrient (carbon, phosphorus, nitrogen, iron) limitation, while this
      was significantly different between the samples of different origin. Thus
      drinking water microbiological quality and biological stability could change
      during different seasons, and the extent of these changes depends on water
      temperature, the water source and treatment. Furthermore, differences in primary
      growth limiting nutrients in different water sources could contribute to
      biological instability in the network, where mixing occurs.

PMID- 29448080
TI  - Can breast characteristics predict upper torso musculoskeletal pain?
AB  - BACKGROUND: Several studies have associated a large breast size with an increased
      prevalence and severity of musculoskeletal pain, particularly pain in the upper
      torso. Despite this evidence, no research has explored whether breast size or
      related characteristics are risk factors for upper torso musculoskeletal pain.
      METHODS: A backward multiple regression analysis was performed to identify
      whether characteristics of the breasts and upper torso, as well as physical
      factors known to be associated with musculoskeletal pain, could predict
      musculoskeletal pain among a cohort of 378 Australian women aged 18 years and
      over who had a wide range of breast sizes. FINDINGS: The model identified that
      breast volume, age and nipple-to-nipple distance predicted 23% of the variance in
      upper torso musculoskeletal pain reported by the participants. INTERPRETATION:
      Women with a larger breast volume, lower age and a greater nipple-to-nipple
      distance were predicted to report a higher upper torso musculoskeletal pain
      score.

PMID- 29448081
TI  - Medial tilting of the joint line in posterior stabilized total knee arthroplasty
      increases contact force and stress.
AB  - BACKGROUND: Kinematically aligned total knee arthroplasty is based on the concept
      to represent the premorbid joint alignment with cruciate-retaining implants,
      characterized by medial tilt and internal rotation. However, kinematic and
      kinetic effects of kinematically aligned total knee arthroplasty with posterior
      stabilized implants is unknown. The purpose of this study was to examine the
      effect of medial tilting of the joint line with posterior-stabilized implants.
      METHODS: A mechanical alignment model, and medial tilt 3 degrees  and 5 degrees 
      models were constructed. Knee kinematics and contact forces were simulated using
      a musculoskeletal computer simulation model. Contact stresses on the tibiofemoral
      joint and the post area were then calculated using finite element analysis.
      FINDINGS: From 0 degrees  to 120 degrees  of knee flexion, greater external
      rotation of the femoral component was observed in medial tilt models (-0.6
      degrees , 1.8 degrees  and 4.2 degrees  in mechanical alignment, medial tilt 3
      degrees  and medial tilt 5 degrees  models, respectively). The peak contact
      stresses on the tibiofemoral joint and the post area at 120 degrees  of knee
      flexion were higher in medial tilt models. The peak contact stresses on the post
      area in medial tilt 3 degrees  and 5 degrees  models were 2.2 and 3.8 times
      greater than that in mechanical alignment model, respectively. INTERPRETATION:
      Medial tilting of the joint line causes greater axial rotation even with
      posterior-stabilized implants, which can represent near-normal kinematics.
      However, medial tilting of the joint line in total knee arthroplasty with
      posterior-stabilized implants may have a higher risk for polyethylene wear at the
      tibiofemoral joint and post area, leading to subsequent component loosening.

PMID- 29448082
TI  - Large enthesophytes in teenage skulls: Mechanical, inflammatory and genetic
      considerations.
AB  - BACKGROUND: The literature implies that large enthesophytes are exclusive to
      genetically predisposed individuals and to Spondyloarthropathies sufferers.
      Accordingly, the aim of this investigation and report was to assess the
      involvement of genetic predisposition, inflammatory and/or mechanical influences
      in the development of large enthesophytes in a sample population of teenagers
      presenting with large enthesophytes emanating from the external occipital
      protuberance. METHODS: Analysis was based on four teenage males (13-16 year-old)
      possessing 14.5-30.5 mm enthesophytes projecting from the external occipital
      protuberance. This study included assessment of radiographs, MRI scans, blood
      work, history, the SF-36 health survey, and the comparison of these data with the
      relevant literature to describe the interrelationships between the presence of
      enlarged external occipital protuberance, forward head protraction, active
      inflammation and/or genetic factors. FINDINGS: Known genetic markers (e.g. HLA
      B27) were not detected by allele-specific primers and both ESR and CRP tests were
      negative. Additionally, MRI analyses failed to detect active localised
      inflammation at the external occipital protuberance and surrounding structures.
      The health survey yielded normal parameters for all participants. All
      participants displayed significantly large Forward Head Protraction values (>40
      mm), and interviews with participants and their parents indicated that concerns
      related to posture were prevalent since early childhood. INTERPRETATION: This
      report suggests that mechanical load has an important role in enthesophyte
      development, irrespective the involvement of inflammatory or genetic factors.

PMID- 29448083
TI  - Sympathetic arousal, but not disturbed executive functioning, mediates the
      impairment of cognitive flexibility under stress.
AB  - Cognitive flexibility emerges from an interplay of multiple cognitive systems, of
      which lexical-semantic and executive are thought to be the most important. Yet
      this has not been addressed by previous studies demonstrating that such forms of
      flexible thought deteriorate under stress. Motivated by these shortcomings, the
      present study evaluated several candidate mechanisms implied to mediate the
      impairing effects of stress on flexible thinking. Fifty-seven healthy adults were
      randomly assigned to psychosocial stress or control condition while assessed for
      performance on cognitive flexibility, working memory capacity, semantic fluency,
      and self-reported cognitive interference. Stress response was indicated by
      changes in skin conductance, hearth rate, and state anxiety. Our analyses showed
      that acute stress impaired cognitive flexibility via a concomitant increase in
      sympathetic arousal, while this mediator was positively associated with semantic
      fluency. Stress also decreased working memory capacity, which was partially
      mediated by elevated cognitive interference, but neither of these two measures
      were associated with cognitive flexibility or sympathetic arousal. Following
      these findings, we conclude that acute stress impairs cognitive flexibility via
      sympathetic arousal that modulates lexical-semantic and associative processes. In
      particular, the results indicate that stress-level of sympathetic activation may
      restrict the accessibility and integration of remote associates and bias the
      response competition towards prepotent and dominant ideas. Importantly, our
      results indicate that stress-induced impairments of cognitive flexibility and
      executive functions are mediated by distinct neurocognitive mechanisms.

PMID- 29448084
TI  - Radiotherapy Controversies and Prospective in Head and Neck Cancer: A Literature
      Based Critical Review.
AB  - In treating head and neck cancer (HNC), the objectives are provided for best
      functional results and minimal risk of serious complications. The choice of
      appropriate management depends primarily on specific site and stage of primary
      tumor at diagnosis. Radiation therapy (RT) with or without concomitant
      chemotherapy represents a classical treatment option. In this review, we provide
      an update of recent research strategies to counteract the existing damage caused
      by RT and highlight clinical trials currently in progress. We discuss the
      challenges in the evaluation of new stage system and RT-related toxicity onset.
      We mainly address the deficiencies and the advantages noted in the current
      treatment era.

PMID- 29448086
TI  - Exposure to diisodecyl phthalate exacerbated Th2 and Th17-mediated asthma through
      aggravating oxidative stress and the activation of p38 MAPK.
AB  - Diisodecyl phthalate (DIDP) is considered to be one of the less toxic phthalates.
      However epidemiological studies suggest that DIDP is associated with the
      occurrence of asthma. The effect of DIDP exposure on allergic asthma and the
      underlying mechanism have not been fully elucidated. Here, mice were exposed to
      DIDP and sensitization with OVA. The results demonstrated that DIDP exposure
      aggravated allergic asthma. Exposure to 15 mg/kg/day DIDP markedly exacerbated
      airway remodeling and promoted airway hyperresponsiveness (AhR). The study
      suggests that exposure to DIDP not only promotes a predominant Th2 response, but
      also induces Th17-type immunity. The induced allergic asthma was accompanied by
      elevation of IgE, an increase in TSLP expression and exacerbation of oxidative
      stress. Inhibition of oxidative stress by Vitamin E effectively alleviated the
      airway remodeling and AhR induced by DIDP and OVA sensitization. Treatment with
      Vitamin E inhibited the Th2 response and the production of TSLP. Blocking the
      activation of p38 MAPK by SB203580 prevented elevation of IL-1beta and IL-17A
      induced by DIDP and OVA sensitization and effectively alleviated Th17 type
      asthmatic lesions. These results suggest that exposure to DIDP exacerbates the
      Th2 and Th17 response through aggravating oxidative stress and activation of the
      p38 MAPK pathway.

PMID- 29448085
TI  - Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship
      to mTOR Signaling.
AB  - Plk2 is a target of p53. Our previous studies demonstrated that with wild-type
      p53, Plk2 impacts mTOR signaling in the same manner as TSC1, and Plk2-deficient
      tumors grew larger than control. Other investigators have demonstrated that Plk2
      phosphorylates mutant p53 in a positive feedback loop. We investigated Plk2's
      tumor suppressor functions in relationship to mTOR signaling. Archival specimens
      from 12 colorectal adenocarcinomas were stained for markers including Plk2,
      phosphorylated mTOR (serine 2448) and ribosomal S6 (Serine 235/236). We show that
      Plk2 is expressed in normal colon, with a punctate staining pattern in
      supranuclear cytoplasm. In colorectal adenocarcinoma, Plk2 demonstrates complete
      or partial loss of expression. Strong expression of phosphorylated mTOR is
      observed in the invasive front. Phosphorylated S6 expression partially correlates
      with phosphorylated mTOR expression but appears more diffuse in some cases. p53
      and Ki67 expression is diffuse, in the subset of cases examined. In order to
      determine whether Plk2 is lost prior to the development of invasive cancer, 8
      colon polyps from 6 patients were evaluated for Plk2 expression. All polyps are
      positive for Plk2. A Cancer Genome Atlas search identified Plk2 mutations to be
      infrequent in colorectal adenocarcinomas. Neither Plk2 methylation (in the gene
      body) nor copy number variations correlated with changes in mRNA expression
      levels. Loss of Plk2 expression along with accentuated expression of
      phosphorylated mTOR and phosphorylated S6 at the invasive front in some
      colorectal carcinomas is consistent with previous findings that an interaction
      between Plk2 and TSC1 / mTOR signaling molecules plays a role in tumor
      suppression. Plk2 protein expression is lost at the same stage in colorectal
      carcinogenesis as p53. The p53 dependence of Plk2 loss and tumor suppressor
      function in relationship to mTOR signaling may have therapeutic implications.

PMID- 29448087
TI  - Assessment of mitochondrial function following short- and long-term exposure of
      human bronchial epithelial cells to total particulate matter from a candidate
      modified-risk tobacco product and reference cigarettes.
AB  - Mitochondrial dysfunction caused by cigarette smoke is involved in the oxidative
      stress-induced pathology of airway diseases. Reducing the levels of harmful and
      potentially harmful constituents by heating rather than combusting tobacco may
      reduce mitochondrial changes that contribute to oxidative stress and cell damage.
      We evaluated mitochondrial function and oxidative stress in human bronchial
      epithelial cells (BEAS 2B) following 1- and 12-week exposures to total
      particulate matter (TPM) from the aerosol of a candidate modified-risk tobacco
      product, the Tobacco Heating System 2.2 (THS2.2), in comparison with TPM from the
      3R4F reference cigarette. After 1-week exposure, 3R4F TPM had a strong inhibitory
      effect on mitochondrial basal and maximal oxygen consumption rates compared to
      TPM from THS2.2. Alterations in oxidative phosphorylation were accompanied by
      increased mitochondrial superoxide levels and increased levels of oxidatively
      damaged proteins in cells exposed to 7.5 MUg/mL of 3R4F TPM or 150 MUg/mL of
      THS2.2 TPM, while cytosolic levels of reactive oxygen species were not affected.
      In contrast, the 12-week exposure indicated adaptation of BEAS-2B cells to long
      term stress. Together, the findings indicate that 3R4F TPM had a stronger effect
      on oxidative phosphorylation, gene expression and proteins involved in oxidative
      stress than TPM from the candidate modified-risk tobacco product THS2.2.

PMID- 29448088
TI  - Antioxidant activity and total phenolic content of ethanolic extract of
      pomegranate peels, juice and seeds.
AB  - Pomegranate (Punica granatum L.) is extensively cultivated in Middle East
      especially in Iran. For centuries, this fruit has been used in Iranian herbal
      medicine. Pomegranate peel, seed and juice contain considerable amounts of
      phenolic compounds and have antioxidant activity. Pomegranate peels, juice and
      seeds from three regions of Natanz, Shahreza, and Doorak were obtained.
      Antioxidant activity, total phenolic, flavonoids, and flavonols contents of
      pomegranate peels, seeds and juices extracts were analyzed. The beta-carotene
      bleaching test and Folin-Ciocalteu method were applied in this study. The
      pomegranate peel extract showed high levels of antioxidant activity in comparison
      to seeds and juices. Doorak peel by 58% had the highest antioxidant activity
      among two other peels. Total phenolics, flavonoids, and flavonols contents of
      pomegranate peel were evaluated much more higher than seeds and juices. The
      significant positive correlation between antioxidant activity and total phenolics
      was reported. According to achieved results, high antioxidant capacity of
      pomegranate especially peel, had shed light to use them as natural food
      preservatives.

PMID- 29448089
TI  - Probabilistic estimates of heterocyclic amines and polycyclic aromatic
      hydrocarbons concentrations in meats and breads applicable to exposure
      assessments.
AB  - Random effect meta-regressions were constructed to estimate concentrations of two
      heterocyclic amines (HCA) and eight polycyclic aromatic hydrocarbons (PAH) in
      meat and breads. Eighteen HCA studies and nine PAH studies of food concentration
      were assembled. Concentration was computed for beef, poultry, pork, and seafood,
      and bread. Fixed effect predictors included cooking time, form of the food,
      cooking method, interaction between form and cooking method, temperature at which
      the food was cooked, fuel of the flame source, percentage of fat, and other
      elements. Meat type was significant to all HCAs but only three of the PAHs.
      Cooking method or an interaction between cooking method and food form was
      significant in all the overall models for each compound, and 80% of models
      created for stratifications of the data based on meat type. Improvement on
      compilations such as the Computerized Heterocyclic Amines Resource for Research
      in Epidemiology of Disease (CHARRED) database comes from inclusion of additional
      studies, PAH compounds, more generalizable food categories, more cooking methods
      (such as smoking), and addition of seafood. Meta-regression allows parameters to
      be estimated with separation of between-study heterogeneity, and extrapolation of
      exposures to more foods. Resulting uncertainty estimates are useful in a
      probabilistic exposure assessment.

PMID- 29448090
TI  - UHPLC-QTOF-MS analysis of bioactive constituents from two Romanian Goji (Lycium
      barbarum L.) berries cultivars and their antioxidant, enzyme inhibitory, and real
      time cytotoxicological evaluation.
AB  - Goji (Lycium barbarum L.) berries are emphasized as healthy food or are used
      widely as dietary supplements. In the present study, the antioxidant and enzyme
      inhibitory activities of berries extracts from two selected Romanian cultivars
      (cv. Erma and cv. Biglifeberry) have been evaluated. UHPLC-QTOF-MS analysis
      results revealed the presence of organic acids, phenolic acids, flavonoids, fatty
      acids (oxylipins), and spermidine derivatives. In particular, cv. Erma showed an
      important tyrosinase-inhibitory effect, whereas, cv. Biglifeberry had a superior
      antioxidant capacity. Particularly, results provided by the CUPRAC assay showed
      the highest antioxidant capacity values (26.91 mg TE/g and 35.41 mg TE/g, for
      'Erma' and 'Biglifeberry', respectively). Toxicological properties of the
      extracts were evaluated with human embryonic kidney cells (HEK-293) using the
      cytotoxicity analysis platform iCELLigence, real-time and label-free impedance
      technology. No cytotoxic effects were observed in a time- and dose-dependent
      manner. Overall, Goji berries are a rich source of bioactive compounds with
      functional properties that need further risk/benefit evaluation when used in
      foods or health-promoting formulations.

PMID- 29448091
TI  - Evidence and prospective of plant derived flavonoids as antiplatelet agents:
      Strong candidates to be drugs of future.
AB  - Platelets are involved in hemostasis, inflammation, and thrombosis processes.
      Following a vascular damage, the endothelium releases protein factors, allowing
      the adhesion of subendothelium to platelets. Then platelets are activated,
      leading to the secretion of biologically-active ligands including thromboxane A2,
      adenosine diphosphate and serotonin. Aspirin, clopidogrel and warfarin are the
      most common drugs used to meet the challenges of platelet aggregation. However,
      these agents face issues with aspirin resistance and bleeding. New
      therapeutically effective and safe agents are therefore strongly needed, and
      natural substances could be ideal candidates. Flavonoids, a chemically diverse
      group of polyphenols, might be important in this regard. Consumption of
      flavonoids is responsible for several health-promoting properties. A number of
      flavonoids have shown outstanding preclinical antiplatelet effects through
      various mechanisms. Flavonoids could provide an ideal approach as templates for
      new, clinically-effective and safe antiplatelet agents due to their inherent
      safety and multiple useful pharmacological hits. This review aims to report data
      from literature regarding flavonoids with antiplatelet activity, with a
      particular focus on possible mechanisms of action, pharmacokinetic profiles and
      overall safety, thus providing a strong rationale for the design of selective and
      well-directed antiplatelet agents of natural origin.

PMID- 29448092
TI  - Investigation on bisphenol A levels in human milk and dairy supply chain: A
      review.
AB  - Bisphenol A (BPA), widely used as additive in food packaging, is an environmental
      and food contaminant that shows a weak estrogenic activity in general population
      and toxicity in the infant population. A temporary tolerable daily intake (t-TDI)
      of 4 MUg/kg bw/day and a migration limit of 0.6 mg/kg in food from plastic
      materials, intended to come in contact with food, were fixed. Dietary milk is
      important in the human diet. The review investigated the contamination levels in
      human milk and along the dairy supply chain. Despite the reported levels are
      generally below the fixed limits, breast milk is considered a continuous low
      level exposure to endocrine-active compounds for infants. In addition, BPA
      residues are detected in milk and dairy products posing a risk to human health.
      BPA enters into milk chain via multiple pathways at various points during milk
      production (e.g., PVC tubing used during the milking process, transfer from bulk
      milk to storage tanks, during milk processing). To prevent or mitigate this
      hazard, a specific TDI for infants is recommended and evaluation of risk factors
      at each phase of the dairy supply chain, in the quality systems, is recommended.

PMID- 29448093
TI  - Probabilistic assessment of dietary exposure to heterocyclic amines and
      polycyclic aromatic hydrocarbons from consumption of meats and breads in the
      United States.
AB  - This probabilistic analysis estimated daily dietary exposures of the US
      population to heterocyclic amines and polycyclic aromatic hydrocarbons from meat
      and some varieties of bread. Mean concentrations for these foods grouped by
      cooking method and food form were combined with consumption data from the
      National Health and Nutritional Examination Survey (NHANES). Mean exposure to
      HCA2 (PhIP + MeIQx), was 565.3 ng/day (95% CrI: 403.73, 726.88), and to PAH8 (sum
      of BaP, ChY, BaA, BkF, BbF, DahA, IP, and BghiP), was 634.8 ng/day (568.38,
      701.15). HCA2 exposures were not significantly different between meat types, but
      multiple differences were found between cooking types. Exposures to PAH8 in the
      mean consumers differed significantly between cooking methods, and were higher
      for beef than poultry (mean difference: 983 ng, 95%CrI: -77.0, 4076.0) and pork
      (990 ng, 95%CrI: 23.7, 4061.8), but not for any other food comparisons. Tradeoffs
      between exposures associated with a typical portion size of potential food
      replacements were also examined. Differences in HCA2 and PAH8 exposure are
      primarily driven by the preparation method rather than the type of meat. These
      findings should be considered in future studies linking PAH and HCA compounds
      with human health impacts.

PMID- 29448094
TI  - The prevalence and antimicrobial resistance of Listeria spp in raw milk and
      traditional dairy products delivered in Yazd, central Iran (2016).
AB  - Listeria monocytogenes is an important foodborne pathogen which its data in
      Iranian dairy products is limited. A total of 545 samples of traditional dairy
      products (raw milk, traditional cheese, traditional butter, traditional curd, and
      traditional ice cream) were collected from traditional dairy shops located in
      Yazd, Iran. L. monocytogenes was isolated, and positive samples were confirmed by
      polymerase chain reaction. Antibiotic sensitivity test was conducted to determine
      the antibiotic resistance. Listeria species were isolated from 11.7% samples.
      4.03% samples were identified as L. monocytogenes, 5.6% as L. innocua, 1.8% as L.
      seeligeri, and 0.18% L. murrayi. All L. monocytogenes isolates were resistant to
      tetracycline, chloramphenicol, penicillin, and amoxicillin/clavulanic acid.
      Consumption of raw milk and its traditional products prepared inadequate heat
      treatment and the lack of appropriate control measures might lead to serious
      health problems. As our results show, the Iranian food safety authorities should
      set up an effective standard to screen all susceptible food for the presence of
      Listeria spp.

PMID- 29448095
TI  - Advances in analytical tools for high throughput strain engineering.
AB  - The emergence of inexpensive, base-perfect genome editing is revolutionising
      biology. Modern industrial biotechnology exploits the advances in genome editing
      in combination with automation, analytics and data integration to build high
      throughput automated strain engineering pipelines also known as biofoundries.
      Biofoundries replace the slow and inconsistent artisanal processes used to build
      microbial cell factories with an automated design-build-test cycle, considerably
      reducing the time needed to deliver commercially viable strains. Testing and
      hence learning remains relatively shallow, but recent advances in analytical
      chemistry promise to increase the depth of characterization possible. Analytics
      combined with models of cellular physiology in automated systems biology
      pipelines should enable deeper learning and hence a steeper pitch of the learning
      cycle. This review explores the progress, advances and remaining bottlenecks of
      analytical tools for high throughput strain engineering.

PMID- 29448096
TI  - AMPK alleviates endoplasmic reticulum stress by inducing the ER-chaperone ORP150
      via FOXO1 to protect human bronchial cells from apoptosis.
AB  - Chronic obstructive pulmonary disease (COPD), is characterized by inflammation of
      airways accompanied by a progressive destruction of lung parenchyma. This process
      is initiated in most cases by cigarette smoking. In this study we investigated
      the role of AMP activated protein kinase (AMPK) in cigarette smoke extract (CSE)
      induced airway epithelial cell apoptosis as a consequence of endoplasmic
      reticulum stress (ER stress). Exposure of human bronchial epithelial cells
      (HBEpC) to CSE resulted in apoptosis as detected using Annexin V-PI flow
      cytometry. However, co-treatment with N1-(beta-d-ribofuranosyl)-5-aminoimidazole
      4-carboxamide (AICAR), a pharmacological activator of AMPK, significantly
      increased cell protection against ER stress-induced apoptosis by upregulating the
      150 kDa oxygen-regulated protein (ORP150), which functions as an ER-associated
      chaperone, with concomitant elevation of FOXO1, a critical transcription factor
      regulating ORP150 expression. Lentiviral silencing of AMPK or FOXO1 using short
      hairpin (sh) RNA resulted in a significant decrease of ORP150 and an elevation of
      CCAAT/enhancer-binding protein-homologous protein (CHOP) resulting in ER stress
      and apoptosis of HBEpC. Together, our results strongly suggest that AMPK can
      activate ORP150 through FOXO1 pathway and confer protection against ER stress
      induced apoptosis of airway epithelial cells following exposure to CSE. Thus,
      AMPK may serve as a likely therapeutic target for clinical and sub-clinical
      interventions in COPD.

PMID- 29448098
TI  - Differences in TLR7/8 activation between monocytes and macrophages.
AB  - The recognition of single-stranded RNA by TLR7/8 leads to the production of NF
      kappaB-mediated cytokines and type I IFNs. However, the role of TLR7/8 activation
      in monocytes and macrophages is still unclear. The aim of this study was to
      investigate the differences in the activation of TLR7/8 between these two cell
      types. Microarray analysis, qRT-PCR and flow cytometry were used to analyse
      TLR7/8 signalling pathways in monocytes and macrophages after stimulation with
      agonists. Our data indicated that TLR8 agonists activated the NF-kappaB- and IRF
      mediated pathways in THP-1 cells, whereas TLR7 agonists did not. However, silent
      TLR8 and enhanced TLR7 expression could increase TLR7-induced NF-kappaB
      activation in monocytes. TLR7 and TLR8 agonists induced NF-kappaB activation but
      no ISG response in PMA-differentiated THP-1 cells. The mRNA levels of pro
      inflammatory cytokine were elevated upon CL075 stimulation in macrophages
      compared to monocytes. Thus, TLR7 and TLR8 might modulate different immune
      responses in monocytes and macrophages.

PMID- 29448097
TI  - Selective degradation of BET proteins with dBET1, a proteolysis-targeting
      chimera, potently reduces pro-inflammatory responses in lipopolysaccharide
      activated microglia.
AB  - Bromodomain and extraterminal (BET) proteins are essential to pro-inflammatory
      gene transcription. The BET family proteins, BRD2, BRD3, BRD4, and testis
      specific BRDT, couple chromatin remodeling to gene transcription, acting as
      histone acetyltransferases, scaffolds for transcription complexes, and markers of
      histone acetylation. To initiate an inflammatory response, cells undergo de novo
      gene transcription requiring histone-modifying proteins to make DNA wrapped
      around histones more or less readily available to transcription complexes.
      Because BET proteins are the gatekeepers of nuclear factor-kappaB (NF-kappaB)
      dependent gene transcription, we hypothesized that degradation of BET proteins,
      particularly BRD2 and BRD4, with the proteolysis-targeting chimera (PROTAC) dBET1
      would dampen the pro-inflammatory response in microglia subjected to
      lipopolysaccharide (LPS) challenge. Degradation of BRD2 and BRD4 was associated
      with significantly reduced expression of several pro-inflammatory genes:
      inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin
      (IL)-1beta, tumor necrosis factor-a (TNF-alpha), IL-6, chemokine (C-C motif)
      ligand 2 (CCL2), and matrix metalloproteinase-9 (MMP-9). This is the first study
      showing that dBET1-mediated targeted degradation of BET proteins robustly dampens
      pro-inflammatory responses in LPS-stimulated microglia. These data suggest that
      BET degradation with dBET1 will likely reduce expression of pro-inflammatory
      genes in in vivo neuroinflammatory models associated with microglial/immune cell
      activation.

PMID- 29448099
TI  - JAB1 regulates CPNE1-related differentiation via direct binding to CPNE1 in HiB5
      hippocampal progenitor cells.
AB  - Copine1 (CPNE1), has tandem C2 domains and an A domain. We previously
      demonstrated that CPNE1 directly induces neuronal differentiation via Protein
      kinase B (AKT) phosphorylation in the hippocampal progenitor cell line, HiB5. To
      better understand its cellular function, we carried out a yeast two-hybrid
      screening to find CPNE1 binding partners. Among the identified proteins, Jun
      activation domain-binding protein 1 (JAB1) appears to directly interact with
      CPNE1. Between CPNE1 and JAB1, the physical interaction was confirmed in vitro
      and in vivo. In addition the specific binding regions of CPNE1 and JAB1 was
      confirmed with truncated mutant assay. Furthermore, our results also demonstrate
      that AKT phosphorylation and expression of the neuronal marker protein are
      increased when JAB1 is overexpressed in CPNE1 high expressed HiB5 cells.
      Moreover, overexpression of both CPNE1 and JAB1 in HiB5 cells effectively
      increased neurite outgrowth. Collectively, our findings suggest that JAB1
      activates the neuronal differentiation ability of CPNE1 through the binding of
      C2A domain in CPNE1 with MPN domain in JAB1.

PMID- 29448100
TI  - Post-ischemic administration of 5-methoxyindole-2-carboxylic acid at the onset of
      reperfusion affords neuroprotection against stroke injury by preserving
      mitochondrial function and attenuating oxidative stress.
AB  - We previously reported that 5-methoxyindole-2-carboxylic acid (MICA) could induce
      preconditioning effect in the ischemic brain of rat. In the present study, we
      addressed the question of whether MICA could also trigger a postconditioning
      effect in ischemic stroke. To this end, MICA (100 mg/kg body weight) was injected
      intraperitoneally at the onset of 24 h reperfusion following 1 h ischemia in rat
      brain. Results indicate that stroked animals treated with MICA showed less brain
      infarction volume than that of vehicle-treated animals. Further experiments
      revealed that brain mitochondrial complexes I and IV showed elevated enzymatic
      activities in MICA treated group and the elevation in complex I activity was
      likely contributed by seemingly enhanced expression of many complex I subunits,
      which was determined by mass spectral peptide sequencing. When compared with
      vehicle-treated rats, the preservation of complexes I and IV activities was shown
      to be accompanied by enhanced mitochondrial membrane potential, increased ATP
      production, and decreased caspase-3 activity. Additional studies also indicate
      the involvement of NQO1 upregulation by the Nrf2 signaling pathway in this MICA
      postconditioning paradigm. Consequently, attenuated oxidative stress in the MICA
      treated group reflected by decrease in H2O2 production and protein carbonylation
      and lipid peroxidation was detected. Taken together, the present study
      demonstrates that MICA can also induce a postconditioning effect in the ischemic
      brain of rat and the underlying mechanism likely involves preservation of
      mitochondrial function, upregulation of cellular antioxidative capacity, and
      attenuation of oxidative stress.

PMID- 29448101
TI  - Neuronal calcium channel alpha1 subunit interacts with AMPA receptor, increasing
      its cell surface localisation.
AB  - Voltage-activated Ca2+ channels (Cav) play critical roles in excitable cells
      including neurons. Unlike the well-defined roles of Cav2 for pre-synaptic
      neurotransmission, the post-synaptic function of Cav2 is unclear. Based on our
      previous study demonstrating the postsynaptic association of the Cav2 with the
      AMPA receptor (AMPA-R), in this study we sought to further analyse the Cav2-AMPA
      R association. We used a step-by-step dissociation of partially purified native
      Cav2-AMPA-R complexes and co-immunoprecipitation of the Cav2-AMPA-R complexes
      expressed in HEK293T cells to demonstrate that the main subunit of Cav, alpha1,
      formed a complex with the AMPA-R without the auxiliary subunits beta,
      alpha2delta, gamma2/3. The alpha1 subunit increased the cell-surface localisation
      of the AMPA-R, which could be a post-synaptic function of the Cav2.

PMID- 29448102
TI  - A universal mini-vector and an annealing of PCR products (APP)-based cloning
      strategy for convenient molecular biological manipulations.
AB  - Currently, the most widely used strategies for molecular cloning are sticky-end
      ligation-based cloning, TA cloning, blunt-end ligation-based cloning and ligase
      independent cloning. In this study we have developed a novel mini-vector pANY1
      which can simultaneously meet the requirements of all these cloning strategies.
      In addition, the selection of appropriate restriction digestion sites is
      difficult in some cases because of the presence of internal sites. In this study,
      an annealing of PCR products (APP)-based sticky-end cloning strategy was
      introduced to avoid this issue. Additionally, false positives occur during
      molecular cloning, which increases the workload of isolating positive clones. The
      plasmid pANY1 contains a ccdB cassette between multiple cloning sites, which
      efficiently avoids these false positives. Therefore, this mini-vector should
      serve as a useful tool with wide applications in biosciences, agriculture, food
      technologies, etc.

PMID- 29448103
TI  - FGF 21 deficiency slows gastric emptying and reduces initial blood alcohol
      concentration in mice exposed to acute alcohol in fasting state.
AB  - Excess alcohol consumption can lead to alcoholic liver disease. Fibroblast growth
      factor 21 (FGF21) is a metabolic regulator with multiple physiologic functions.
      Previous study demonstrated that FGF21 deficiency exacerbated alcohol-induced
      liver injury and exogenous FGF21 administration protected liver from chronic
      alcohol-induced injury. In this study, we aimed to explore the role of FGF21 in
      alcohol metabolism in mice. FGF21 knockout (KO) mice and the wild type(WT)
      control mice were divided into two groups and fasted for 24 h followed by a bonus
      of alcohol treatment at a dose of 5 g/kg body weight via gavage. Serum alcohol
      concentration was measured after gavage at 0.5, 2, 3, 4 and 6 h, respectively. At
      the end, gastric and liver tissues were collected. Serum alcohol concentration of
      KO mice was significantly lower than that of WT at 0.5 h after alcohol expose.
      There were no significant differences in alcohol dehydrogenase (ADH) activity and
      aldehyde dehydrogenase 2 (ALDH2) activity in gastric and liver tissues between WT
      and the KO mice. However, gastric emptying time of KO mice was much longer than
      that of WT mice. In addition, the intestinal permeability and serum GLP-1 level
      of KO mice were significantly higher than that of WT mice. These results suggest
      that FGF21 deficiency slow gastric emptying rate and indirectly influence initial
      alcohol metabolism in mice exposed to acute alcohol. Our findings provide
      additional information for understanding the gastrointestinal mechanism of
      alcoholic liver disease and other alcohol use disorders.

PMID- 29448104
TI  - AIM2 regulates vascular smooth muscle cell migration in atherosclerosis.
AB  - BACKGROUND: Atherosclerosis (AS) is a common pathological basis of various
      cardiovascular and cerebrovascular diseases. Plaque formation is initiated and
      triggered by vascular smooth musclecells (VSMCs) migration in vascular wall,
      which gradually aggravates atherosclerosis progression. Absent in melanoma 2
      (AIM2), a member of HIN-200 family, plays an important role in activating
      inflammasome. However, the role of AIM2 in atherosclerotic plaque progression
      outside of the inflammasome has not yet been reported. METHODS: The potential
      effect and the underlying mechanism of AIM2 were investigated in apoliporotein E
      deficient (ApoE-/-) mice. Murine AIM2 lentivirus, shRNA-AIM2 lentivirus and null
      lentivirus were constructed and injected intravenously into ApoE-/- mice, which
      were fed on a high fat diet. The specific mechanism of AIM2 in vascular smooth
      cells (VSMCs) was explored in vitro. RESULTS: Results showed the aortic
      atherosclerotic lesion area was larger with AIM2 over-expression, and the number
      of smooth muscle cells was enhanced in line with the increased AIM2 levels. AIM2
      overexpression also induced the increasing expression of MMP2. In vitro studies
      revealed that different levels of ox-LDL increased AIM2 expression in a time
      dependent manner. Transwell showed that AIM2 mediated migration in VSMCs. The
      expression of AIM2 can be inhibited when the ROS inhibitor was used.
      Additionally, the overexpression and inhibition of AIM2 significantly affects HG
      induced migration and TGF-beta/SMAD signaling pathway in VSMCs. CONCLUSION: Thus,
      we demonstrated that AIM2 could promote the progression of atherosclerotic plaque
      by increasing migration in VSMCs.

PMID- 29448105
TI  - Casein kinase 2 phosphorylates and stabilizes C/EBPbeta in pancreatic beta cells.
AB  - During the development of type 2 diabetes, endoplasmic reticulum (ER) stress
      leads to pancreatic beta cell failure. CCAAT/enhancer-binding protein (C/EBP)
      beta is highly induced by ER stress and AMP-activated protein kinase (AMPK)
      suppression in pancreatic beta cells, and its accumulation reduces pancreatic
      beta cell mass. We investigated the phosphorylation state of C/EBPbeta under
      these conditions. Casein kinase 2 (CK2) was found to co-localize with C/EBPbeta
      in MIN6 cells. It phosphorylated S222 of C/EBPbeta, a previously unidentified
      phosphorylation site. We found that C/EBPbeta is phosphorylated by CK2 under AMPK
      suppression and ER stress, which are important from the viewpoint of the
      worsening pathological condition of type 2 diabetes, such as decreased insulin
      secretion and apoptosis of pancreatic beta cells.

PMID- 29448106
TI  - Folic acid prevents methotrexate-induced epithelial-mesenchymal transition via
      suppression of secreted factors from the human alveolar epithelial cell line
      A549.
AB  - Methotrexate (MTX) often induces serious lung diseases such as pulmonary
      fibrosis. Although MTX is known to be a folic acid (FA) antagonist, the effect of
      FA on MTX-induced lung injury remains unclear. Recent studies indicate that
      epithelial-mesenchymal transition (EMT) is involved in pulmonary fibrosis. Here,
      we aimed to clarify the effect of FA on MTX-induced EMT in human alveolar
      epithelial cell line A549 using conditioned medium (CM). CM was prepared from the
      supernatants of A549 cells treated with MTX in the absence (CMM) or presence
      (CMMF) of FA. FA suppressed EMT-like morphological changes and elevated
      mRNA/protein expression levels of alpha-smooth muscle actin induced by MTX in
      A549 cells. In addition, CMM induced EMT-like phenotypical changes, whereas CMMF
      had no effect on the phenotype of A549 cells, indicating that FA may suppress MTX
      induced EMT via inhibiting the secretion of certain factors into the supernatant
      of the cells. Furthermore, FA also prevented CMM-induced EMT-like phenotypical
      changes in A549 cells. These findings indicate that FA may be a useful
      pharmaceutical for MTX-induced lung injury.

PMID- 29448107
TI  - Decrease in the cytosolic NADP+-dependent isocitrate dehydrogenase activity
      through porcine sperm capacitation.
AB  - In order to understand the molecular mechanisms involved in the sperm
      capacitation, we have identified the proteins tyrosine-phosphorylated during the
      capacitation especially in conjunction with the regulation of the levels of
      reactive oxygen species (ROS) in sperm. In the present study, the effects of the
      tyrosine phosphorylation of cytosolic NADP+-dependent isocitrate dehydrogenase
      (IDPc) on its catalytic activity and on the levels of ROS in sperm have been
      studied. The tyrosine phosphorylated IDPc showed a significantly lowered
      enzymatic activity. The immunocytochemical analyses using the highly specific
      antisera against IDPc revealed that IDPc was mainly localized to the principal
      piece of the porcine sperm flagellum. As IDPc is one of the major NADPH
      regenerating enzymes in porcine sperm, it is strongly suggested that the decrease
      in IDPc activity is involved in the increased levels of ROS, which results in the
      induction of hyperactivated flagellar movement and capacitation.

PMID- 29448108
TI  - Inhibition of HMGB1 mediates neuroprotection of traumatic brain injury by
      modulating the microglia/macrophage polarization.
AB  - Microglia/Macrophages have a double-edged role in secondary brain damage after
      traumatic brain injury (TBI) depending on polarization toward proinflammatory M1
      or anti-inflammatory M2 phenotypes. Recently, high-mobility group box 1 (HMGB1)
      was found to influence the polarization of macrophages. In this study,
      glycyrrhizin (GL), an inhibitor of HMGB1, was used to investigate whether the
      inhibition of HMGB1 could modulate microglia/macrophage polarization after TBI.
      The results showed that treatment with GL improved the neurological function
      recovery, reduced the lesion volume, and inhibited the release and expression of
      HMGB1 after TBI. In addition, the administration of GL suppressed M1 phenotype
      activation and promoted M2 phenotype activation of microglia/macrophages. In
      conclusion, the results suggested that GL attenuated TBI by inhibiting M1
      phenotype while inducing M2 phenotype activation of microglia/macrophages, at
      least partly through inhibiting HMGB1. Also, targeting HMGB1 to modulate the
      microglia/macrophage polarization should be one potential therapeutic approach
      for TBI.

PMID- 29448109
TI  - HDAC1 regulates the stability of glutamate carboxypeptidase II protein by
      modulating acetylation status of lysine 479 residue.
AB  - Our previous study showed that the level of glutamate carboxypeptidase II (GCPII)
      protein is regulated by valproic acid, a histone deacetylase (HDAC) inhibitor,
      through acetylation of lysine residue in the GCPII protein in human astrocytes, U
      87MG. The present study further investigated which HDAC subtype is involved in
      the acetylation of GCPII. The results revealed that GCPII interacted with HDAC1
      but not with HDAC2, HDAC3, HDAC4, HDAC5, and HDAC6. Overexpression of catalytic
      domain (1-56 aa)-deleted HDAC1, which poorly binds to GCPII, enhanced lysine
      acetylation in GCPII and increased the level of GCPII protein when compared with
      that of the wild-type HDAC1. Further experiments showed that HDAC1 regulated the
      stability of GCPII protein. These data suggest that acetylation of GCPII is
      facilitated by HDAC1, and the acetylated GCPII is more stable than the non
      acetylated GCPII. Additional experiments using siRNA HDAC1 and by HDAC1
      overexpression confirmed the role of HDAC1 in regulating the stability of GCPII
      protein. Further, database search of acetylation and ubiquitination sites showed
      four candidate lysine sites in human GCPII protein that can be both acetylated
      and ubiquitinylated (K207, K479, K491, and K699). Mutation (lysine residues to
      arginine (R)) analysis showed that in the presence of cycloheximide K479R- and
      K491R-hGCPII mutants were less ubiquitinylated and degraded, and decrease in the
      level of GCPII protein by HDAC1 was significantly blocked by K479R mutants. These
      data suggest that K479 is a possible site of acetylation or ubiquitination.
      Furthermore, the results also demonstrate that the stability of GCPII protein is
      regulated by HDAC1 through acetylation at the lysine 479 residue.

PMID- 29448110
TI  - A set of 14 DIP-SNP markers to detect unbalanced DNA mixtures.
AB  - Unbalanced DNA mixture is still a difficult problem for forensic practice. DIP
      STRs are useful markers for detection of minor DNA but they are not widespread in
      the human genome and having long amplicons. In this study, we proposed a novel
      type of genetic marker, termed DIP-SNP. DIP-SNP refers to the combination of
      INDEL and SNP in less than 300bp length of human genome. The multiplex PCR and
      SNaPshot assay were established for 14 DIP-SNP markers in a Chinese Han
      population from Shanxi, China. This novel compound marker allows detection of the
      minor DNA contributor with sensitivity from 1:50 to 1:1000 in a DNA mixture of
      any gender with 1 ng-10 ng DNA template. Most of the DIP-SNP markers had a
      relatively high probability of informative alleles with an average I value of
      0.33. In all, we proposed DIP-SNP as a novel kind of genetic marker for detection
      of minor contributor from unbalanced DNA mixture and established the detection
      method by associating the multiplex PCR and SNaPshot assay. DIP-SNP polymorphisms
      are promising markers for forensic or clinical mixture examination because they
      are shorter, widespread and higher sensitive.

PMID- 29448111
TI  - In silico screening of proteins targeting circulating miRNAs for improved
      diagnosis of multiple myeloma.
AB  - Multiple Myeloma (MM) is a B-cell malignancy, which is characterized by the
      expansion of clonal plasma cells in the bone marrow, leading to abnormal
      accumulation of monoclonal antibodies in circulation. Certain circulating miRNAs
      are deregulated in MM and their differential expression profiles in body fluids
      can be quantified and used to discriminate between the premalignant and malignant
      stages of MM. Our study identifies protein which would show affinity for a
      selected panel of circulating miRNAs deregulated in MM. Human RNA binding
      proteins were identified based on their unique RNA binding domains and their
      interacting probabilities with the panel of miRNAs deregulated in MM. miR-26 was
      used as a negative control for interaction studies. 3-D structure of candidate
      proteins were determined and molecular docking was performed to confirm the
      results. Five RNA binding proteins TROVE2, CUGBP2, DHX8, PUM2 and DKC1 were used
      for molecular docking studies. DKC1 showed significant hydrogen bonding as well
      as remarkable binding affinity values of -17.4 kcal/mol with miR-720 (2 H-bonds),
      -16 kcal/mol with miR-1246 (1 H-bond) and -16.9 kcal/mol with miR-1308 (3 H
      bonds). Identified protein-miRNA interaction could be used to develop an
      economical and reliable ELISA based methodology for improved and sensitive
      diagnosis of MM patients.

PMID- 29448112
TI  - LIF and multiple sclerosis: One protein with two healing properties.

PMID- 29448113
TI  - Face-to-face anti-tobacco intervention lowers cotinine level in asthmatic
      children.

PMID- 29448114
TI  - Safe and effective intradermal influenza vaccine desensitization for delayed
      influenza vaccine allergy.

PMID- 29448115
TI  - Asthma mobile applications: Are they ready for prime time?

PMID- 29448116
TI  - Immunoliposomes in clinical oncology: State of the art and future perspectives.
AB  - Liposomal formulations entrapping a vast number of molecules have improved cancer
      therapies overcoming certain pharmacokinetic (PK) and pharmacodynamic
      limitations, many of which are associated with tumor characteristics. In this
      context, immunoliposomes represent a new strategy that has been widely
      investigated in preclinical cancer models with promising results, although few
      have reached the stage of clinical trials. This contrasts with the emerging
      clinical application of monoclonal antibodies (mAbs). This formulation allows the
      conjugation of different mAbs or antibody derivatives, such as monovalent
      variable fragments Fab', to the polymers covering the surface of liposomes. The
      combination of this targeting strategy together with drug encapsulation in a
      single formulation may contribute to enhance the efficacy of these associated
      agents, reducing their toxicities. In this paper we will consider how factors
      such as particle size, lipid composition and charge, lipid-polymer conjugation,
      method of production and type of ligand for liposome coupling influence the
      efficacy of these formulations. Furthermore, the high inter-individual
      variability in the tumor microenvironment, as well as the poor experimental
      designs for the PK characterization of liposomes, make the establishment of the
      relationship between plasma or tumor concentrations and efficacy difficult. Thus,
      adequate dosing regimens and patient stratification regarding the target
      expression may contribute to enhance the possibility of incorporating these
      immunoliposomes into the therapeutic arsenal for cancer treatments. All these
      issues will be briefly dealt with here, together with a section showing the state
      of the art of those targeted liposomes that are coming up for testing in clinical
      trials. Finally, some insights into future developments such as the combination
      of specificity and controlled release, based on the application of different
      stimuli, for the manipulation of stability and cargo release, will be offered.
      This has been included in order to highlight the new opportunities for targeted
      liposomes, including immunoliposomes.

PMID- 29448117
TI  - Refractory focal epilepsy in a paediatric patient with primary familial brain
      calcification.
AB  - Primary familial brain calcification (PFBC), otherwise known as Fahr's disease,
      is a rare autosomal dominant condition with manifestations of movement disorders,
      neuropsychiatric symptoms, and epilepsy in a minority of PFBC patients. The
      clinical presentation of epilepsy in PFBC has not been described in detail. We
      present a paediatric patient with PFBC and refractory focal epilepsy based on
      seizure semiology and ictal EEG, but with generalized interictal EEG
      abnormalities. The patient was found to have a SLC20A2 mutation known to be
      pathogenic in PFBC, as well as a variant of unknown significance in SCN2A. This
      case demonstrates that the ictal EEG is important for accurately classifying
      epilepsy in affected subjects with PFBC. Further, epilepsy in PFBC may be a
      polygenic disorder.

PMID- 29448118
TI  - Calcium channel blockers as drug repurposing candidates for gestational diabetes:
      Mining large scale genomic and electronic health records data to repurpose
      medications.
AB  - New therapeutic approaches are needed for gestational diabetes mellitus (GDM),
      but must show safety and efficacy in a historically understudied population. We
      studied associations between electronic medical record (EMR) phenotypes and
      genetic variants to uncover drugs currently considered safe in pregnancy that
      could treat or prevent GDM. We identified 129 systemically active drugs
      considered safe in pregnancy targeting the proteins produced from 196 genes. We
      tested for associations between GDM and/or type 2 diabetes (DM2) and 306 SNPs in
      130 genes represented on the Illumina Infinium Human Exome Bead Chip (DM2 was
      included due to shared pathophysiological features with GDM). In parallel, we
      tested the association between drugs and glucose tolerance during pregnancy as
      measured by the glucose recorded during a routine 50-g glucose tolerance test
      (GTT). We found an association between GDM/DM2 and the genes targeted by 11 drug
      classes. In the EMR analysis, 6 drug classes were associated with changes in GTT.
      Two classes were identified in both analyses. L-type calcium channel blocking
      antihypertensives (CCBs), were associated with a 3.18 mg/dL (95% CI -6.18 to 
      0.18) decrease in glucose during GTT, and serotonin receptor type 3 (5HT-3)
      antagonist antinausea medications were associated with a 3.54 mg/dL (95% CI 1.86
      5.23) increase in glucose during GTT. CCBs were identified as a class of drugs
      considered safe in pregnancy could have efficacy in treating or preventing GDM.
      5HT-3 antagonists may be associated with worse glucose tolerance.

PMID- 29448119
TI  - Estimation of hepatic fat fraction using modified Dixon magnetic resonance
      imaging techniques: effect of liver cirrhosis.
AB  - PURPOSE: To evaluate modified Dixon MRI techniques in hepatic fat estimation and
      to assess the effect of cirrhosis. METHODS: 235 patients who underwent liver MRI
      were included. Correlation between modified Dixon techniques with MRS was
      assessed. Accuracy of MR techniques in hepatic fat estimation was calculated, and
      the result was compared between patients with/without liver cirrhosis. RESULTS:
      Correlation between modified Dixon and MRS was better in group without liver
      cirrhosis, and accuracy of modified Dixon method was higher in group without
      liver cirrhosis. CONCLUSIONS: Modified Dixon techniques estimate hepatic fat
      fraction noninvasively, but the result can be influenced by the presence of liver
      cirrhosis.

PMID- 29448120
TI  - Imaging features of malignant abdominal neuroendocrine tumors with rare
      presentation.
AB  - BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (NETs) are rare entities
      arising from neuroendocrine cells in the gastroenteric tract and pancreas. The
      purpose of this article is to present four cases of gastroenteropancreatic NETs
      that featured a challenging diagnosis. CASE PRESENTATION: We report a case series
      of four NETs, each with different features. All NETs were suspected based on
      clinical and biochemical data. The workup of the abnormalities was performed with
      CT, PET or MRI. CONCLUSION: The diagnosis of NETs is challenging and generally
      based on clinical manifestations, blood biochemical tests, imaging techniques,
      and pathology.

PMID- 29448121
TI  - Neonatal distal femoral physeal injury secondary to mechanical trauma of birth: A
      case report.
AB  - Physeal injuries occurring secondary to neonatal birth-related trauma are rare
      entities. Most reported cases of physeal injury involve the distal humerus with
      only a few published case reports of proximal femoral involvement. So far, we
      have found only one reported case of neonatal distal femoral epiphysiolysis
      following Caesarean section. We hereby report a unique case of distal femoral
      physeal injury with at least partial epiphyseal separation following an
      uneventful, spontaneous vaginal delivery. Given the uneventful delivery and no
      known prenatal risk factors, the imaging findings were initially not recognized
      as being secondary to birth-related injury. Nonaccidental trauma and infection
      were considered among the possible etiologies for the clinical and imaging
      findings and a detailed workup for both these entities was performed. Distal
      femoral physeal injury was considered as a diagnosis of exclusion only after both
      initial differential considerations were excluded. The authors hope that a
      knowledge of this entity will facilitate a more accurate differential in cases of
      thigh swelling and hypomobility in the newborn.

PMID- 29448122
TI  - Value of 18F-FET PET in adult brainstem glioma.
AB  - PURPOSE: To investigate 18F-fluoro-ethyl-tyrosine positron emission tomography
      (FET-PET) imaging characteristics of adult brainstem glioma (BSG). MATERIALS AND
      METHODS: FET-PET imaging and progression-free survival (PFS) of 16 adult patients
      with BSG was analyzed (9 high-grade gliomas, 7 low-grade gliomas). SUVmax, TBR,
      and time activity curves of FET-PET were calculated. RESULTS: Progressive gliomas
      had higher SUVmax (3.57 +/- 1.47 vs. 1.60 +/- 0.51; p = 0.003) and TBRmax (3.00
      +/- 1.12 vs. 1.36 +/- 0.33; p = 0.001) than stable gliomas. Kaplan-Meier analysis
      showed longer PFS of tumors with TBRmax < 2.0 compared to tumors with TBRmax >
      2.0 (665 +/- 32 days versus 220 +/- 39 days; p < 0.001). CONCLUSION: FET-PET
      uptake might be associated with disease progression in adult BSG.

PMID- 29448123
TI  - Imaging features of pancreatic metastases: A comparison with pancreatic ductal
      adenocarcinoma.
AB  - PURPOSE: To compare imaging features of pancreatic metastases (PM) with those of
      pancreatic ductal adenocarcinomas (PDAC). METHODS: CT and MR scans of 24 patients
      with 54 PM and 30 patients with PDAC were reviewed to evaluate the imaging
      features, which were compared by using a Chi square test. RESULTS: We found a
      statistically significant difference between PM and PDAC based on location (P <
      0.001), margins (P < 0.001), arterial enhancement (P = 0.004), rim enhancement (P
      < 0.001), pancreatic duct dilatation (P = 0.01), common bile duct dilatation (P =
      0.003), vascular involvement (P = 0.02), parenchymal atrophy (P < 0.001),
      peripancreatic fluid (P = 0.03). CONCLUSION: Imaging features might be helpful to
      differentiate PM from PDAC.

PMID- 29448124
TI  - Anatomy and pathology of the canal of Nuck.
AB  - The canal of Nuck is the female equivalent of the processus vaginalis in the male
      but is less well known than its male counterpart. It is a rare entity not
      commonly encountered by radiologists, particularly in the adult population.
      Knowledge of the embryology and anatomy of the canal of Nuck is essential for
      identification of the various pathologic conditions that may occur in this
      location. Moreover, radiologists should be familiar with this entity to compose
      an appropriate and thorough differential diagnosis of a labial mass/swelling. In
      this review, we discuss both the anatomy and the more common pathology that can
      be encountered within it.

PMID- 29448125
TI  - A critical review of histopathological findings associated with endocrine and non
      endocrine hepatic toxicity in fish models.
AB  - Although frequently examined as a target organ for non-endocrine toxicity,
      histopathological evaluation of the liver is becoming a routine component of
      endocrine disruption studies that utilize various fish species as test subjects.
      However, the interpretation of microscopic liver findings can be challenging,
      especially when attempting to distinguish adverse changes associated with
      endocrine disrupting substances from those caused by systemic or direct hepatic
      toxicity. The purpose of this project was to conduct a critical assessment of the
      available peer-reviewed and grey literature concerning the histopathologic
      effects of reproductive endocrine active substances (EAS) and non-endocrine
      acting substances in the livers of fish models, and to determine if liver
      histopathology can be used to reliably distinguish endocrine from non-endocrine
      etiologies. The results of this review suggest that few compound-specific
      histopathologic liver effects have been identified, among which are estrogen
      agonist-induced increases in hepatocyte basophilia and proteinaceous
      intravascular fluid in adult male teleosts, and potentially, decreased hepatocyte
      basophilia in female fish exposed to substances that possess androgenic, anti
      estrogenic, or aromatase inhibitory activity. This review also used published
      standardized methodology to assess the credibility of the histopathology data in
      each of the 117 articles that reported liver effects of treatment, and
      consequently it was determined that in only 37% of those papers were the data
      considered either highly credible or credible. The outcome of this work
      highlights the value of histopathologic liver evaluation as an investigative tool
      for EAS studies, and provides information that may have implications for EAS
      hazard assessment.

PMID- 29448126
TI  - Sub-lethal effects of herbicides penoxsulam, imazamox, fluridone and glyphosate
      on Delta Smelt (Hypomesus transpacificus).
AB  - Concerns regarding non-target toxicity of new herbicides used to control invasive
      aquatic weeds in the San Francisco Estuary led us to compare sub-lethal toxicity
      of four herbicides (penoxsulam, imazamox, fluridone, and glyphosate) on an
      endangered fish species Delta Smelt (Hypomesus transpacificus). We measured
      17beta-estradiol (E2) and glutathione (GSH) concentrations in liver, and
      acetylcholinesterase (AChE) activity in brain of female and male fish after 6 h
      of exposure to each of the four herbicides. Our results indicate that fluridone
      and glyphosate disrupted the E2 concentration and decreased glutathione
      concentration in liver, whereas penoxsulam, imazamox, and fluridone inhibited
      brain AChE activity. E2 concentrations were significantly increased in female and
      male fish exposed to 0.21 MUM of fluridone and in male fish exposed to 0.46, 4.2,
      and 5300 MUM of glyphosate. GSH concentrations decreased in males exposed to
      fluridone at 2.8 MUM and higher, and glyphosate at 4.2 MUM. AChE activity was
      significantly inhibited in both sexes exposed to penoxsulam, imazamox, and
      fluridone, and more pronounced inhibition was observed in females. The present
      study demonstrates the potential detrimental effects of these commonly used
      herbicides on Delta Smelt.

PMID- 29448127
TI  - Trophic transfer potential of two different crystalline phases of TiO2 NPs from
      Chlorella sp. to Ceriodaphnia dubia.
AB  - Owing to the increase in the usage of titanium dioxide nanoparticles (TiO2 NPs),
      their release into the aquatic environment is inevitable. In the aquatic
      ecosystem, TiO2 NPs can bio-magnify at various trophic levels in the food chain
      through dietary exposure. In the current study, the trophic transfer potential of
      two crystalline phases of TiO2, anatase and rutile nanoparticles (individual as
      well as a binary mixture) has been evaluated in the lake water matrix using algae
      daphnia system. Chlorella sp. and Ceriodaphnia dubia were used as test organisms
      to represent the algae-daphnia food chain of the freshwater ecosystem. Other than
      crystallinity, the effect of irradiation (visible and UV-A) was also investigated
      at the test concentrations, 75, 300, and 1200 MUM. TiO2 NPs treated algal diet
      produced significant mortality only at the test concentrations, 300 and 1200 MUM.
      The type of irradiation and crystallinity doesn't have any impact on the
      mortality of daphnids through the dietary exposure of TiO2 NPs. Comparing the
      mixture with individual NPs, binary mixture induced less mortality on C. dubia
      which signifies the antagonistic effect of NPs when they coexist. Statistical
      modeling confirmed the antagonistic effect of the binary mixture on C. dubia. As
      individual NPs, anatase and rutile forms showed a maximum Ti accumulation under
      UV-A and visible irradiation, respectively. BMF of TiO2 NPs has been in
      validation with the bioaccumulation noted in C. dubia. Individual NPs (75 MUM)
      showed higher BMF value of ~23 under both UV-A (anatase) and visible (rutile)
      irradiation. Individual NPs showing higher BMF confirmed their trophic transfer
      potential in the aquatic food chain, primarily through the diet. In contrast, the
      binary mixture obtained a higher BMF of 1.9 and 0.79 at 75 and 300 MUM under
      visible and UV-A irradiation, respectively. The plausible reason behind this
      decrement was the antagonistic effect of the mixture which significantly reduced
      their Ti bioaccumulation on C. dubia.

PMID- 29448129
TI  - Studies to enhance the hyperpolarization level in PHIP-SAH-produced C13-pyruvate.
AB  - The use of [1-13C]pyruvate, hyperpolarized by dissolution-Dynamic Nuclear
      Polarization (d-DNP), in in vivo metabolic studies has developed quickly, thanks
      to the imaging probe's diagnostic relevance. Nevertheless, the cost of a d-DNP
      polarizer is quite high and the speed of hyperpolarization process is relatively
      slow, meaning that its use is limited to few research laboratories. ParaHydrogen
      Induced Polarization Side Arm Hydrogenation (PHIP-SAH) (Reineri et al., 2015) is
      a cost effective and easy-to-handle method that produces 13C-MR hyperpolarization
      in [1-13C]pyruvate and other metabolites. This work aims to identify the main
      determinants of the hyperpolarization levels observed in C13-pyruvate using this
      method. By dissecting the various steps of the PHIP-SAH procedure, it has been
      possible to assess the role of several experimental parameters whose optimization
      must be pursued if this method is to be made suitable for future translational
      steps. The search for possible solutions has led to improvements in the
      polarization of sodium [1-13C]pyruvate from 2% to 5%. Moreover, these results
      suggest that observed polarization levels could be increased considerably by an
      automatized procedure which would reduce the time required for the work-up
      passages that are currently carried out manually. The results reported herein
      mean that the attainment of polarization levels suitable for the metabolic
      imaging applications of these hyperpolarized substrates show significant promise.

PMID- 29448128
TI  - Hubs in the human fetal brain network.
AB  - Advances in neuroimaging and network analyses have lead to discovery of highly
      connected regions, or hubs, in the connectional architecture of the human brain.
      Whether these hubs emerge in utero, has yet to be examined. The current study
      addresses this question and aims to determine the location of neural hubs in
      human fetuses. Fetal resting-state fMRI data (N = 105) was used to construct
      connectivity matrices for 197 discrete brain regions. We discovered that within
      the connectional functional organization of the human fetal brain key hubs are
      emerging. Consistent with prior reports in infants, visual and motor regions were
      identified as emerging hub areas, specifically in cerebellar areas. We also found
      evidence for network hubs in association cortex, including areas remarkably close
      to the adult fusiform facial and Wernicke areas. Functional significance of hub
      structure was confirmed by computationally deleting hub versus random nodes and
      observing that global efficiency decreased significantly more when hubs were
      removed (p < .001). Taken together, we conclude that both primary and association
      brain regions demonstrate centrality in network organization before birth. While
      fetal hubs may be important for facilitating network communication, they may also
      form potential points of vulnerability in fetal brain development.

PMID- 29448130
TI  - Optimized slice-selective 1H NMR experiments combined with highly accurate
      quantitative 13C NMR using an internal reference method.
AB  - Isotope ratio monitoring by 13C NMR spectrometry (irm-13C NMR) provides the
      complete 13C intramolecular position-specific composition at natural abundance.
      It represents a powerful tool to track the (bio)chemical pathway which has led to
      the synthesis of targeted molecules, since it allows Position-specific Isotope
      Analysis (PSIA). Due to the very small composition range (which represents the
      range of variation of the isotopic composition of a given nuclei) of 13C natural
      abundance values (500/00), irm-13C NMR requires a 10/00 accuracy and thus highly
      quantitative analysis by 13C NMR. Until now, the conventional strategy to
      determine the position-specific abundance xi relies on the combination of irm-MS
      (isotopic ratio monitoring Mass Spectrometry) and 13C quantitative NMR. However
      this approach presents a serious drawback since it relies on two different
      techniques and requires to measure separately the signal of all the carbons of
      the analyzed compound, which is not always possible. To circumvent this
      constraint, we recently proposed a new methodology to perform 13C isotopic
      analysis using an internal reference method and relying on NMR only. The method
      combines a highly quantitative 1H NMR pulse sequence (named DWET) with a 13C
      isotopic NMR measurement. However, the recently published DWET sequence is
      unsuited for samples with short T1, which forms a serious limitation for irm-13C
      NMR experiments where a relaxing agent is added. In this context, we suggest two
      variants of the DWET called Multi-WET and Profiled-WET, developed and optimized
      to reach the same accuracy of 10/00 with a better immunity towards T1 variations.
      Their performance is evaluated on the determination of the 13C isotopic profile
      of vanillin. Both pulse sequences show a 10/00 accuracy with an increased
      robustness to pulse miscalibrations compared to the initial DWET method. This
      constitutes a major advance in the context of irm-13C NMR since it is now
      possible to perform isotopic analysis with high relaxing agent concentrations,
      leading to a strong reduction of the overall experiment time.

PMID- 29448131
TI  - Chirp echo Fourier transform EPR-detected NMR.
AB  - A new ultra-wide band (UWB) pulse EPR method is introduced for observing all
      nuclear frequencies of a paramagnetic center in a single shot. It is based on
      burning spectral holes with a high turning angle (HTA) pulse that excites
      forbidden transitions and subsequent detection of the hole pattern by a chirp
      echo. We term this method Chirp Echo Epr SpectroscopY (CHEESY)-detected NMR. The
      approach is a revival of FT EPR-detected NMR. It yields similar spectra and the
      same type of information as electron-electron double resonance (ELDOR)-detected
      NMR, but with a multiplex advantage. We apply CHEESY-detected NMR in Q band to
      nitroxides and correlate the hyperfine spectrum to the EPR spectrum by varying
      the frequency of the HTA pulse. Furthermore, a selective pi pulse before the HTA
      pulse allows for detecting hyperfine sublevel correlations between transitions of
      one nucleus and for elucidating the coupling regime, the same information as
      revealed by the HYSCORE experiment. This is demonstrated on
      hexaaquamanganese(II). We expect that CHEESY-detected NMR is generally applicable
      to disordered systems and that our results further motivate the development of
      EPR spectrometers capable of coherent UWB excitation and detection, especially at
      higher fields and frequencies.

PMID- 29448132
TI  - MU-Calpain (CAPN1), calpastatin (CAST), and growth hormone receptor (GHR) genetic
      effects on Angus beef heifer performance traits and reproduction.
AB  - Genetic marker effects and type of inheritance are estimated with poor precision
      when minor marker allele frequencies are low. An Angus population was subjected
      to marker assisted selection for multiple years to equalize CAPN1 haplotypes,
      CAST, and GHR genetic marker frequencies. The objective was to estimate the
      pleiotropic effects of these carcass quality oriented markers for body weight,
      reproduction, and first calf performance traits in 174 replacement beef females
      which were managed under 2 post-weaning development protocols. Heifers were
      weighed at 11-, 12-, and 13-mo, at first breeding season pregnancy evaluation,
      and prior to first calving season. Pubertal status was determined at 11-, 12-,
      and 13-mo of age. Antral follicles were counted, reproductive tracts were scored,
      and tract dimensions were measured at 13-mo. Body condition and hip height were
      scored and measured at pregnancy evaluation and prior to calving season. Heifer
      pregnancy and weaning rates and ordinal birth date were recorded. Calf body
      weights at birth and weaning were analyzed. Single df linear contrasts for
      recessive effects of the GHR heterozygous genotype showed significant decreases
      of 2.5-3.6% in 11-, 12-, and 13-mo heifer body weights and heifer weight prior to
      calving. The additive differences between GHR homozygotes were small and not
      significant for all body weights measured but a 1 wk difference in calf birth
      date was significant. For all 13-mo uterine measurements, scores, and antral
      follicle counts, only the CAST dominance contrast for medium antral follicle
      count was significant. The CAPN1 haplotype with a strong additive effect for
      increased beef tenderness also had a significant additive effect on calving date.
      Heifers homozygous for the tender haplotype calved 7.9 days later than heifers
      homozygous for the tough haplotype. Most heifer reproductive traits were not
      significantly affected by CAST and CAPN1 markers that are widely used to improve
      beef tenderness by selection and breeders should not be concerned with how these
      markers affect reproduction and other heifer traits with the possible exception
      of CAPN1 effects on calving date.

PMID- 29448133
TI  - Exposure to the ROCK inhibitor fasudil promotes gliogenesis of neural stem cells
      in vitro.
AB  - Fasudil is a clinically approved Rho-associated protein kinase (ROCK) inhibitor
      that has been used widely to treat cerebral consequences of subarachnoid
      hemorrhage. It is known to have a positive effect on animal models of
      neurological disorders including Parkinson's disease and stroke. However, its
      cellular effect on progenitor populations and differentiation is not clearly
      understood. While recent studies suggest that fasudil promotes the mobilization
      of neural stem cells (NSCs) from the subventricular zone in vivo and promotes the
      differentiation of the C17.2 cerebellar neuroprogenitor line in vitro, it is
      unclear whether fasudil is involved in the differentiation of primary NSCs. Here,
      we tested the effect of fasudil on mouse NSCs in vitro, and observed increased
      gliogenesis in NSCs derived from lateral ventricles. Upon treatment, fasudil
      promoted characteristics of neurogenesis including phenotypic changes in neural
      outgrowth and interkinetic nuclear-like movements as an immediate response, while
      Sox2 expression was maintained and GFAP expression increased. Moreover, the
      gliogenic response to fasudil medium was observed in both early postnatal and
      adult NSC cultures. Taken together, our results show that fasudil promotes the
      differentiation of NSCs into astroglial lineage, suggesting that it could be used
      to develop novel vitro gliogenesis models and regulate differentiation for neural
      repair.

PMID- 29448134
TI  - Enhancing proliferation and optimizing the culture condition for human bone
      marrow stromal cells using hypoxia and fibroblast growth factor-2.
AB  - This study aimed to determine the cellular characteristics and behaviors of human
      bone marrow stromal cells (hBMSCs) expanded in media in a hypoxic or normoxic
      condition and with or without fibroblast growth factor-2 (FGF-2) treatment.
      hBMSCs isolated from the vertebral body and expanded in these four groups were
      evaluated for cellular proliferation/migration, colony-forming units, cell
      surface characterization, in vitro differentiation, in vivo transplantation, and
      gene expression. Culturing hBMSCs using a particular environmental factor
      (hypoxia) and with the addition of FGF-2 increased the cellular proliferation
      rate while enhancing the regenerative potential, modulated the multipotency
      related processes (enhanced chondrogenesis-related processes/osteogenesis, but
      reduced adipogenesis), and increased cellular migration and collagen formation.
      The gene expression levels in the experimental samples showed activation of the
      hypoxia-inducible factor-1 pathway and glycolysis in the hypoxic condition, with
      this not being affected by the addition of FGF-2. The concurrent application of
      hypoxia and FGF-2 could provide a favorable condition for culturing hBMSCs to be
      used in clinical applications associated with bone tissue engineering, due to the
      enhancement of cellular proliferation and regenerative potential.

PMID- 29448135
TI  - The effect of adding Coping Power Program-Sweden to Parent Management Training
      effects and moderators in a randomized controlled trial.
AB  - For children with oppositional defiant disorder (ODD), Parent Management Training
      (PMT) is a recommended treatment in addition to child Cognitive Behavioral
      Therapy (child-CBT). There is however a lack of studies investigating the
      additive effect of group-based child-CBT to PMT for children between 8 and 12
      years. The current study investigated the incremental effect of group-based child
      CBT, based on the Coping Power Program, when added to the Swedish group-based PMT
      program KOMET. Outcomes were child behavior problems, child prosocial behavior,
      parenting skills and the moderating effect of child characteristics. One hundred
      and twenty children 8-12 years with ODD or Disruptive Behavioral Disorder NOS and
      their parents were randomized either to combined child-CBT and PMT (n = 63) or to
      PMT only (n = 57) in Swedish Child- and Adolescent Psychiatric settings.
      Participants were assessed pre- and post-treatment using semi-structured
      interviews and child- and parent ratings. After treatment, behavior problems were
      reduced in both groups. Prosocial behavior were significantly more improved in
      the combined treatment. Parenting skills were improved in both groups. In
      moderator analyses, behavior problems and prosocial behavior improved
      significantly more in the combined treatment compared to PMT only in the group of
      children with high levels of ODD symptoms.

PMID- 29448136
TI  - Improving functional outcomes in women with borderline personality disorder and
      PTSD by changing PTSD severity and post-traumatic cognitions.
AB  - Although functional impairment typically improves during evidence-based
      psychotherapies (EBPs) for borderline personality disorder (BPD), functional
      levels often remain suboptimal after treatment. The present pilot study evaluated
      whether and how integrating PTSD treatment into an EBP for BPD would improve
      functional outcomes. Participants were 26 women with BPD, PTSD, and recent
      suicidal and/or self-injurious behavior who were randomized to receive one year
      of Dialectical Behavior Therapy (DBT) or DBT with the DBT Prolonged Exposure (DBT
      PE) protocol for PTSD. Five domains of functioning were assessed at 4-month
      intervals during treatment and at 3-months post-treatment. DBT + DBT PE was
      superior to DBT in improving global social adjustment, health-related quality of
      life, and achieving good global functioning, but not interpersonal problems or
      quality of life. Results of time-lagged mixed effects models indicated that,
      across both treatments, reductions in PTSD severity significantly predicted
      subsequent improvement in global social adjustment, global functioning, and
      health-related quality of life, whereas reductions in post-traumatic cognitions
      significantly predicted later improvement in all functional outcomes except
      global social adjustment. These findings provide preliminary evidence supporting
      the role of change in PTSD severity and trauma-related cognitions as active
      mechanisms in improving functional outcomes among individuals with BPD and PTSD.

PMID- 29448137
TI  - Differential metabolism of L-phenylalanine in the formation of aromatic volatiles
      in melon (Cucumis melo L.) fruit.
AB  - Studies on the active pathways and the genes involved in the biosynthesis of L
      phenylalanine-derived volatiles in fleshy fruits are sparse. Melon fruit rinds
      converted stable-isotope labeled L-phe into more than 20 volatiles.
      Phenylpropanes, phenylpropenes and benzenoids are apparently produced via the
      well-known phenylpropanoid pathway involving phenylalanine ammonia lyase (PAL)
      and being (E)-cinnamic acid a key intermediate. Phenethyl derivatives seemed to
      be derived from L-phe via a separate biosynthetic route not involving (E)
      cinnamic acid and PAL. To explore for a biosynthetic route to (E)-cinnamaldehyde
      in melon rinds, soluble protein cell-free extracts were assayed with (E)-cinnamic
      acid, CoA, ATP, NADPH and MgSO4, producing (E)-cinnamaldehyde in vitro. In this
      context, we characterized CmCNL, a gene encoding for (E)-cinnamic acid:coenzyme A
      ligase, inferred to be involved in the biosynthesis of (E)-cinnamaldehyde.
      Additionally we describe CmBAMT, a SABATH gene family member encoding a benzoic
      acid:S-adenosyl-L-methionine carboxyl methyltransferase having a role in the
      accumulation of methyl benzoate. Our approach leads to a more comprehensive
      understanding of L-phe metabolism into aromatic volatiles in melon fruit.

PMID- 29448138
TI  - Dual-targeting antitumor hybrids derived from Pt(IV) species and millepachine
      analogues.
AB  - Many strategies have been developed to circumvent the shortcomings of Pt(II)
      based chemotherapy, but the inherent problems still have not been effectively
      resolved. Here we report a new series of dual-targeting Pt(IV) prodrugs,
      conjugates of millepachine analogues with the related Pt(IV) complexes derived
      from cisplatin or oxaliplatin, respectively, which can inhibit tubulin
      polymerization and induce DNA damage. Among them, compound 19 possessed excellent
      antitumor activities against the tested human cancer cell lines, and arrested the
      cell cycle at the G2/M phases and ultimately induced cell apoptosis.
      Interestingly, its low cytotoxicity toward two human normal cells and sensitivity
      toward two cisplatin-resistant cells revealed the possibility for cancer therapy.
      More importantly, 19 displayed excellent antitumor efficacy in the SK-OV-3
      xenograft model better than cisplatin and the corresponding millepachine
      analogue. Our research provided an efficient strategy for multi-targeting
      antitumor drug development.

PMID- 29448139
TI  - Discovery and optimization of 1-(1H-indol-1-yl)ethanone derivatives as CBP/EP300
      bromodomain inhibitors for the treatment of castration-resistant prostate cancer.
AB  - The CREB (cAMP responsive element binding protein) binding protein (CBP) and its
      homolog EP300 have emerged as new therapeutic targets for the treatment of cancer
      and inflammatory diseases. Here we report the identification, optimization and
      evaluation of 1-(1H-indol-1-yl)ethanone derivatives as CBP/EP300 inhibitors
      starting from fragment-based virtual screening (FBVS). A cocrystal structure of
      the inhibitor (22e) in complex with CBP provides a solid structural basis for
      further optimization. The most potent compound 32h binds to the CBP bromodomain
      and has an IC50 value of 0.037 MUM in the AlphaScreen assay which was 2 times
      more potent than the reported CBP bromodomain inhibitor SGC-CBP30 in our hands.
      32h also exhibit high selectivity for CBP/EP300 over other bromodomain-containing
      proteins. Notably, the ester derivative (29h) of compound 32h markedly inhibits
      cell growth in several prostate cancer cell lines including LNCaP, 22Rv1 and
      LNCaP derived C4-2B. Compound 29h suppresses the mRNA expression of full length
      AR (AR-FL), AR target genes and other oncogene in LNCaP cells. 29h also reduces
      the expression of PSA, the biomarker of prostate cancer. CBP/EP300 inhibitor 29h
      represents a promising lead compound for the development of new therapeutics for
      the treatment of castration-resistant prostate cancer.

PMID- 29448140
TI  - Synthesis and structure-activity relationships of asymmetric dimeric beta
      carboline derivatives as potential antitumor agents.
AB  - A series of newly asymmetric dimeric beta-carbolines with a spacer of 4-6
      methylene units between the indole nitrogen and the harmine oxygen were
      synthesized. Structures of all the novel synthesized compounds were confirmed by
      their spectral and analytical studies. All of the synthesized compounds were
      screened for their in vitro cytotoxic activity against nine cancer cell lines.
      The results revealed that compounds 7c, 7o and 7s exhibited the highest cytotoxic
      activities with IC50 values of less than 20 MUM against the tumor cell lines
      tested. Acute toxicities and antitumor efficacies of the selected compounds in
      mice were also evaluated, and compound 7o exhibited potent antitumor activities
      with the tumor inhibition rate of over 40%. The wound healing assay displayed a
      specific impairment in the motility of the HT-29 cells, which suggested the anti
      metastatic potential of compound 7o. Moreover, compound 7o had obvious
      angiogenesis inhibitory effects in the chicken chorioallantoic membrane (CAM)
      assay. Preliminary structure-activity relationship (SAR) analysis indicated that:
      (1) 3-phenylpropyl substituent at the N9-position of the indole ring was the most
      suitable group giving rise to potent cytotoxic agents; (2) the spacer length
      affected the antitumor potencies, and four methylene units were more favorable.

PMID- 29448141
TI  - Biocompatible and biodegradable zeolitic imidazolate framework/polydopamine
      nanocarriers for dual stimulus triggered tumor thermo-chemotherapy.
AB  - Zeolitic imidazolate frameworks (ZIFs) have attracted great interest as pH
      sensitive drug carrier because of high drug loading and intrinsic
      biodegradability. In this work, a biocompatible NIR and pH-responsive drug
      delivery nanoplatform based on ZIFs (PDA-PCM@ZIF-8/DOX) is synthesized for in
      vivo cancer therapy. The biocompatibility of ZIFs is greatly improved by
      polydopamine (PDA) modifying and proved by cytotoxicity and in vivo acute
      toxicity evaluation. The degradability is also regulated in an appropriate rate.
      Due to mild reaction condition of ZIFs, the synthesis and drug loading is
      achieved in one pot with high loading (37.86%) and encapsulation rate (78.76%).
      Meanwhile, PDA acts as a photothermal transfer agent to trigger thermal response
      switch of phase change materials for NIR controlled drug release. Under the dual
      stimulus of NIR and acid environment, the drug release is as high as 78%, while
      only 21% is released without stimulus, showing a remarkable effect of control
      release. In vivo anti-tumor experiments demonstrate the high tumor inhibition
      rate of photothermal-chemotherapy group with a significant synergistic effect.
      The biocompatible and biodegradable drug delivery platform based on ZIFs has
      shown great promise for future clinic cancer therapy.

PMID- 29448142
TI  - Metabolomics facilitates the discrimination of the specific anti-cancer effects
      of free- and polymer-conjugated doxorubicin in breast cancer models.
AB  - Metabolomics is becoming a relevant tool for understanding the molecular
      mechanisms involved in the response to new drug delivery systems. The
      applicability of this experimental approach to cell cultures and animal models
      makes metabolomics a useful tool for establishing direct connections between in
      vitro and in vivo data, thus providing a reliable platform for the
      characterization of chemotherapeutic agents. Herein, we used metabolomic profiles
      based on nuclear magnetic resonance (NMR) spectroscopy to evaluate the
      biochemical pathways involved in the response to a chemotherapeutic anthracycline
      drug (Doxorubicin, Dox) and an N-(2-hydroxypropyl) methacrylamide (HPMA)
      copolymer-conjugated form (HPMA-Dox) in an in vitro cell culture model and an in
      vivo orthotopic breast cancer model. We also used protein expression and flow
      cytometry studies to obtain a better coverage of the biochemical alterations
      associated with the administration of these compounds. The overall analysis
      revealed that polymer conjugation leads to increased apoptosis, reduced
      glycolysis, and reduced levels of phospholipids when compared to the free
      chemotherapeutic drug. Our results represent a first step in the application of
      integrated in vitro and in vivo metabolomic studies to the evaluation of drug
      delivery systems.

PMID- 29448143
TI  - Adsorption force of fibronectin controls transmission of cell traction force and
      subsequent stem cell fate.
AB  - The transmission of cell traction force (CTF) to underlying biomaterials is
      essential for adhered cells to measure and respond to their mechanical
      microenvironment. Given that the protein layer adsorbed on materials lies between
      the cells and materials, we hypothesize that the interfacial strength of protein
      material interfaces (i.e., the adsorption force of proteins, Fad) should have an
      important role in regulating the transmission of CTF. To test this hypothesis,
      rat mesenchymal stem cells (rMSCs) were cultured on poly(dimethyl siloxane)
      (PDMS) substrates with different Fad of fibronectin (FN), and the transmission of
      CTF was observed by immunofluorescence staining of FN and deformation of PDMS. As
      revealed, FN on substrates with low Fad is more liable to be desorbed by CTF,
      which prevents the transmission of CTF to substrates. In contrast, high Fad
      facilitates the transmission of CTF from rMSCs to the FN layer and PDMS
      substrates so that rMSCs can perceive the mechanical properties of substrates. We
      further demonstrated that the divergent transmission of CTF on low and high Fad
      substrates regulates the lineage specifications of rMSCs. Our study confirms the
      important role of Fad in CTF transmission and provides a new perspective to gain
      insights into cell-material interactions and cell fates, which may help to guide
      the design of better biomaterials.

PMID- 29448144
TI  - Nanocements produced from mesoporous bioactive glass nanoparticles.
AB  - Biomedical cements are considered promising injectable materials for bone repair
      and regeneration. Calcium phosphate composition sized with tens of micrometers is
      currently one of the major powder forms. Here we report a unique cement form made
      from mesoporous bioactive glass nanoparticles (BGn). The nanopowder could harden
      in reaction with aqueous solution at powder-to-liquid ratios as low as 0.4-0.5
      (vs. 2.0-3.0 for conventional calcium phosphate cement CPC). The cementation
      mechanism investigated from TEM, XRD, FT-IR, XPS, and NMR analyses was
      demonstrated to be the ionic (Si and Ca) dissolution and then reprecipitation to
      form Si-Ca-(P) based amorphous nano-islands that could network the particles. The
      nanopowder-derived nanocement exhibited high surface area (78.7 m2/g);
      approximately 9 times higher than conventional CPC. The immersion of nanocement
      in simulated body fluid produced apatite nanocrystallites with ultrafine size of
      10 nm (vs. 55 nm in CPC). The ultrafine nanocement adsorbed protein molecules
      (particularly positive charged proteins) at substantial levels; approximately 160
      times higher than CPC. The nanocement released Si and Ca ions continuously over
      the test period of 2 weeks; the Si release was unique in nanocement whereas the
      Ca release was in a similar range to that observed in CPC. The release of ions
      significantly stimulated the responses of cells studied (rMSCs and HUVECs). The
      viability and osteogenesis of rMSCs were significantly enhanced by the nanocement
      ionic extracts. Furthermore, the in vitro tubular networking of HUVECs was
      improved by the nanocement ionic extracts. The in vivo neo-blood vessel formation
      in CAM model was significantly higher by the nanocement implant when compared
      with the CPC counterpart, implying the Si ion release might play a significant
      role in pro-angiogenesis. Furthermore, the early bone forming response of the
      nanocement, based on the implantation in a rat calvarial bone defect,
      demonstrated a sign of osteoinductivity along with excellent osteocondution and
      bone matrix formation. Although more studies remain to confirm the potential of
      nanocement, some of the intriguing physico-chemical properties and the biological
      responses reported herein support the promise of the new 'nanopowder-based
      nanocement' for hard tissue repair and regeneration.

PMID- 29448145
TI  - Concurrent nicotine and tobacco product use among homeless smokers and
      associations with cigarette dependence and other factors related to quitting.
AB  - BACKGROUND: Cigarette smoking rates among homeless adults are exceptionally high,
      contributing to health disparities experienced by this disadvantaged population.
      Concurrent nicotine and tobacco product use have been shown to result in greater
      health problems than cigarette smoking alone, and little is known about the
      rates, motives, and perceived impacts of concurrent use in this group. The
      purpose of this study is to explore concurrent use rates and constructs of
      interest among homeless adult daily smokers and to examine differences between
      concurrent users and non-concurrent users on cigarette dependence, perceived risk
      of smoking, readiness to quit, and the receipt of recent cessation intervention.
      METHODS: Participants (N = 396) were recruited from six homeless-serving agencies
      and/or shelters in Oklahoma City. Enrolled participants completed self-report
      questionnaires. RESULTS: The rate of concurrent use was high -67.2%. Participants
      most frequently endorsed lower cost and a desire to cut down on cigarette smoking
      as motives for concurrent product use. Concurrent users indicated both a greater
      likelihood of developing a smoking-related disease if they did not quit for good
      and a greater number of past year quit attempts relative to non-concurrent users.
      There was no significant difference between concurrent users and non-concurrent
      users on readiness to quit or having received recent smoking cessation
      intervention. CONCLUSION: The need for cessation efforts that account for
      concurrent use for homeless adult smokers is great. Study findings indicate that
      concurrent users are commonly pursuing the reduction or elimination of cigarette
      usage and should be specifically targeted for cessation intervention.

PMID- 29448146
TI  - Corrigendum to "Marijuana and tobacco co-use among a nationally representative
      sample of US pregnant and non-pregnant women: 2005-2014 National Survey on Drug
      Use and Health findings" [Drug Alcohol Depend. 177 (2017) 130-135].

PMID- 29448148
TI  - Large inter-rater variability on EEG-reactivity is improved by a novel
      quantitative method.
AB  - OBJECTIVE: To assess inter-rater agreement on EEG-reactivity (EEG-R) in comatose
      patients and compare it with a quantitative method (QEEG-R). METHODS: Six 30-s
      stimulation epochs (noxious, visual and auditory) were performed during EEG on 19
      neurosurgical and 11 cardiac arrest patients. Six experts analysed EEGs for
      reactivity using their habitual methods. QEEG-R was defined as present if >=2/6
      epochs were reactive (stimulation/rest power ratio exceeding noise level). Three
      months patient outcome was assessed by the Cerebral Performance Category Score
      (CPC) dichotomized in good (1-2) or poor (3-5). RESULTS: Agreement among experts
      on overall EEG-R varied from 53% to 83% (kappa: 0.05-0.64) and reached 100%
      (kappa: 1) between two QEEG-R calculators. For the experts, absence of EEG-R
      yielded sensitivities for poor outcome between 40-85% and specificities between
      20-90%, for QEEG-R sensitivity was 40% (CI: 23-68%) and specificity 100% (CI: 69
      100%). CONCLUSIONS: There is a large inter-rater variation among experts on EEG-R
      assessment in comatose patients. QEEG-R is a promising objective prognostic
      parameter with low inter-rater variation and a high specificity for prediction of
      poor outcome. SIGNIFICANCE: Clinicians should be cautious when using the
      traditional, qualitative method, in particular in end-of-life decisions.
      Implementation of the quantitative method in clinical practice may improve
      reliability of reactivity assessments.

PMID- 29448147
TI  - Acceptance and patterns of personal vaporizer use in Australia and the United
      Kingdom: Results from the International Tobacco Control survey.
AB  - BACKGROUND: This study examined the prevalence and correlates of (1) perceived
      social acceptability of personal vaporizer (PV)/e-cigarette use, and (2) reported
      vaping in public and private places, in the UK and Australia with different
      regulatory environments for PVs. METHODS: Data analyzed come from 2849 smokers
      and recent ex-smokers in the UK and Australia who participated in the 2014 wave
      of the International Tobacco Control Survey. RESULTS: UK respondents were more
      likely to think vaping is socially acceptable than Australians (56.4% vs. 27.9%;
      p < 0.001). Having quit smoking, observing vaping in smoke-free (SF) public
      places, and believing vaping is less harmful than smoking was all significantly
      associated with greater perceived social acceptability of vaping in both
      countries. However, vaping status and that of friends and family were more
      influential in Australia than in the UK. Vaping was reported as much more common
      in private, than public, settings in both countries. UK vapers were more likely
      to report vaping in SF public places (OR = 2.66; 95% CI = 1.5-4.7; p < 0.01) and
      at home (OR = 2.44; 95% CI = 1.5-3.9; p < 0.001), but not in their car when
      controlling for demographic factors and vaping and smoking status. CONCLUSION:
      The acceptability of vaping was greater among those who were more exposed to
      vaping and not just among those with some personal experience of vaping,
      suggesting no strong social barriers to increased use. Vaping in SF public places
      was less common than in homes, and both were more common in the UK than in
      Australia, suggesting some social constraints on use, particularly in Australia.

PMID- 29448149
TI  - Characterization of the stimulus waveforms generated by implantable pulse
      generators for deep brain stimulation.
AB  - OBJECTIVE: To determine the circuit elements required to theoretically describe
      the stimulus waveforms generated by an implantable pulse generator (IPG) during
      clinical deep brain stimulation (DBS). METHODS: We experimentally interrogated
      the Medtronic Activa PC DBS IPG and defined an equivalent circuit model that
      accurately captured the output of the IPG. We then compared the detailed circuit
      model of the clinical stimulus waveforms to simplified representations commonly
      used in computational models of DBS. We quantified the errors associated with
      these simplifications using theoretical activation thresholds of myelinated axons
      in response to DBS. RESULTS: We found that the detailed IPG model generated
      substantial differences in activation thresholds compared to simplified models.
      These differences were largest for bipolar stimulation with long pulse widths.
      Average errors were ~3 to 24% for voltage-controlled stimulation and ~2 to 11%
      for current-controlled stimulation. CONCLUSIONS: Our results demonstrate the
      importance of including basic circuit elements (e.g. blocking capacitors, lead
      wire resistance, electrode capacitance) in model analysis of DBS. SIGNIFICANCE:
      Computational models of DBS are now commonly used in academic research,
      industrial technology development, and in the selection of clinical stimulation
      parameters. Incorporating a realistic representation of the IPG output is
      necessary to improve the accuracy and utility of these clinical and scientific
      tools.

PMID- 29448150
TI  - Right prefrontal cortex specialization for visuospatial working memory and
      developmental alterations in prefrontal cortex recruitment in school-age
      children.
AB  - OBJECTIVE: The right prefrontal cortex (PFC) plays an essential role in active
      processing within visuospatial working memory (VSWM). The aim of this study was
      to examine developmental changes in the recruitment patterns of the PFC during
      visuospatial memory tasks in school-age participants. METHODS: We recruited 80
      school-age children who were classified into three age groups: 7- to 8-year-old,
      9- to 10-year-old, and 11- to 12-year-old children. We used near infrared
      spectroscopy (NIRS) to measure PFC activity during visuospatial memory task.
      Memory stimuli were presented either sequentially or simultaneously. RESULTS: In
      all three groups, right-lateralized PFC activity was observed during sequential
      presentation, suggesting specialization of the right PFC for VSWM. During
      simultaneous presentation, right-lateralized PFC activity was not observed in 7-
      to 8-year-old children or 9- to 10-year-old children. In contrast, PFC activity
      was right-lateralized in 11- to 12-year-old children. CONCLUSIONS: We suggest
      that specialization of the right PFC for VSWM is already present before school
      age, but widely distributed activity in response to visuospatial memory tasks
      changes to more focal activity in VSWM-specific regions during the early school
      years. SIGNIFICANCE: Using NIRS, we showed developmental changes in the
      recruitment patterns of the PFC during visuospatial memory tasks.

PMID- 29448152
TI  - The clinical utility of qualitative electroencephalography during tilt table
      testing - A retrospective study.
AB  - OBJECTIVE: To assess electroencephalography (EEG) changes during tilt table
      testing in syncope and other orthostatic syndromes. METHODS: We retrospectively
      reviewed consecutive tilt table studies with simultaneous EEG from April 2014 to
      May 2016 at our center. All patients had video EEG during tilt table. All
      patients had at least 10 min of head up tilt unless they had syncope or did not
      tolerate the study. Video EEG was interpreted by epileptologists. RESULTS: Eighty
      seven patients met the inclusion criteria. Mean age was 45 years, and 55 were
      women. Seven patients (~8%) had syncope during tilt table, 11 patients (~12%) had
      significant neurogenic orthostatic hypotension and a separate group of 11
      patients (~12%) had significant orthostatic tachycardia. Valsalva responses were
      abnormal in 7 of the 11 patients with orthostatic hypotension, suggesting an
      underlying neurogenic orthostatic hypotension. Visually discernable EEG changes
      were seen in only 3 patients (~43%) who had syncope and in 1 patient (~9%) with
      orthostatic tachycardia. CONCLUSIONS: Qualitative EEG analysis based on visual
      inspection during tilt table study revealed abnormalities in less than half the
      patients with syncope and a very small fraction with orthostatic tachycardia.
      SIGNIFICANCE: Routine qualitative EEG recording might not be clinically useful
      during tilt table studies.

PMID- 29448151
TI  - Functional cortical source connectivity of resting state electroencephalographic
      alpha rhythms shows similar abnormalities in patients with mild cognitive
      impairment due to Alzheimer's and Parkinson's diseases.
AB  - OBJECTIVE: This study tested the hypothesis that markers of functional cortical
      source connectivity of resting state eyes-closed electroencephalographic (rsEEG)
      rhythms may be abnormal in subjects with mild cognitive impairment due to
      Alzheimer's (ADMCI) and Parkinson's (PDMCI) diseases compared to healthy elderly
      subjects (Nold). METHODS: rsEEG data had been collected in ADMCI, PDMCI, and Nold
      subjects (N = 75 for any group). eLORETA freeware estimated functional lagged
      linear connectivity (LLC) from rsEEG cortical sources. Area under receiver
      operating characteristic (AUROC) curve indexed the accuracy in the classification
      of Nold and MCI individuals. RESULTS: Posterior interhemispheric and widespread
      intrahemispheric alpha LLC solutions were abnormally lower in both MCI groups
      compared to the Nold group. At the individual level, AUROC curves of LLC
      solutions in posterior alpha sources exhibited moderate accuracies (0.70-0.72) in
      the discrimination of Nold vs. ADMCI-PDMCI individuals. No differences in the LLC
      solutions were found between the two MCI groups. CONCLUSIONS: These findings
      unveil similar abnormalities in functional cortical connectivity estimated in
      widespread alpha sources in ADMCI and PDMCI. This was true at both group and
      individual levels. SIGNIFICANCE: The similar abnormality of alpha source
      connectivity in ADMCI and PDMCI subjects might reflect common cholinergic
      impairment.

PMID- 29448153
TI  - Projecting future climate change impacts on heat-related mortality in large urban
      areas in China.
AB  - Global climate change is anticipated to raise overall temperatures and has the
      potential to increase future mortality attributable to heat. Urban areas are
      particularly vulnerable to heat because of high concentrations of susceptible
      people. As the world's largest developing country, China has experienced
      noticeable changes in climate, partially evidenced by frequent occurrence of
      extreme heat in urban areas, which could expose millions of residents to summer
      heat stress that may result in increased health risk, including mortality. While
      there is a growing literature on future impacts of extreme temperatures on public
      health, projecting changes in future health outcomes associated with climate
      warming remains challenging and underexplored, particularly in developing
      countries. This is an exploratory study aimed at projecting future heat-related
      mortality risk in major urban areas in China. We focus on the 51 largest Chinese
      cities that include about one third of the total population in China, and project
      the potential changes in heat-related mortality based on 19 different global
      scale climate models and three Representative Concentration Pathways (RCPs). City
      specific risk estimates for high temperature and all-cause mortality were used to
      estimate annual heat-related mortality over two future twenty-year time periods.
      We estimated that for the 20-year period in Mid-21st century (2041-2060) relative
      to 1970-2000, incidence of excess heat-related mortality in the 51 cities to be
      approximately 37,800 (95% CI: 31,300-43,500), 31,700 (95% CI: 26,200-36,600) and
      25,800 (95% CI: 21,300-29,800) deaths per year under RCP8.5, RCP4.5 and RCP2.6,
      respectively. Slowing climate change through the most stringent emission control
      scenario RCP2.6, relative to RCP8.5, was estimated to avoid 12,900 (95% CI:
      10,800-14,800) deaths per year in the 51 cities in the 2050s, and 35,100 (95% CI:
      29,200-40,100) deaths per year in the 2070s. The highest mortality risk is
      primarily in cities located in the North, East and Central regions of China.
      Population adaptation to heat is likely to reduce excess heat mortality, but the
      extent of adaptation is still unclear. Future heat mortality risk attributable to
      exposure to elevated warm season temperature is likely to be considerable in
      China's urban centers, with substantial geographic variations. Climate mitigation
      and heat risk management are needed to reduce such risk and produce substantial
      public health benefits.

PMID- 29448154
TI  - A serine carboxypeptidase-like acyltransferase catalyzes synthesis of indole-3
      acetic (IAA) ester conjugate in rice (Oryza sativa).
AB  - Indole-3-acetic acid (IAA) conjugation is one of mechanisms responsible for
      regulation of free auxin levels in plants. A new member of the serine
      carboxypeptidase-like (SCPL) acyltransferases family from Oryza sativa has been
      cloned and characterized. 1-O-indole-3-acetyl-beta-D-glucose (1-O-IAGlc): myo
      inositol acyltransferase (IAInos synthase) is an enzyme of IAA ester conjugates
      biosynthesis pathway that catalyzes transfer of IAA moiety from 1-O-IAGlc to myo
      inositol forming IA-myo-inositol (IAInos). The OsIAA-At cDNA has been cloned and
      expressed using yeast and bacterial expression systems. Proteins produced in
      Saccharomyces cerevisiae and Escherichia coli contained 483 and 517 amino acids,
      respectively. The enzyme functionally expressed in both expression systems
      exhibits 1-O-IAGlc-dependent acyltransferase activity. Analysis of amino acid
      sequence confirmed that rice IAInos synthase belongs to the SCPL protein family.
      Recombinant IAInos synthases produced in yeast and bacterial expression systems
      have been partially characterized and their properties have been compared to
      those of the native enzyme obtained from 6-days-old rice seedlings by biochemical
      approach. The oligosaccharide component of the protein enzyme is not necessary
      for its catalytic activity. The native enzyme showed the lowest specific activity
      of 5.01 nmol min-1 mg-1 protein, whereas the recombinant enzymes produced in
      yeast and bacteria showed specific activity of 18.75 nmol min-1 mg-1 protein and
      18.09 nmol min-1 mg-1 protein, respectively. The KM values for myo-inositol were
      similar for all three forms of the enzyme: 1.38, 0.83, 1.0 mM for native,
      bacterial and yeast protein, respectively. Both recombinant forms of IAInos
      synthase and the native enzyme also have the same optimal pH of 7.4 and all of
      them are inhibited by phenylmethylsulfonyl fluoride (PMSF), specific inhibitor of
      serine carboxypeptidases.

PMID- 29448155
TI  - Characterization of a SUPERMAN-like Gene, MdSUP11, in apple (Malus * domestica
      Borkh.).
AB  - Arabidopsis SUPERMAN and its family members of its family play important roles in
      plant growth and floral organ development; yet much less is known about their
      functions expanding in apple tree development. Previous work has identified 12
      SUP-like genes in the apple (Malus * domestica Borkh.) genome, and the MdSUP11
      which is expressed in both vegetative and reproductive organs of apple. However,
      the function of MdSUP11 remains obscure. In this study, the beta-glucuronidase
      expression driven by the MdSUP11 native promoter was detected in roots, young
      leaves, and floral organs of transgenic Arabidopsis. In transgenic tobacco,
      overexpression of MdSUP11 lead to dwarfism, aberrant leaf shapes, and
      morphological changes of floral organs. Endogenous concentrations of auxin
      (indole-3-acetic acid), abscisic acid, isopentenyl adenosine and zeatin riboside
      were significantly higher in young MdSUP11-transformed tobacco plants than in non
      transformed plants. Gene expression analysis using real-time quantitative PCR
      showed up-regulation of NtDFR2 and NtANS1 expression in unopened transgenic
      flowers, whereas NtCHS expression was not changed significantly. Together, these
      results suggest that MdSUP11 is associated with apple's vegetative and
      reproductive development. Its overexpression in tobacco affects leaf and flower
      organ development and plant height; potentially by changing NtDFR2 and NtANS1
      expression and endogenous levels of indole-3-acetic acid, cytokinins and abscisic
      acid.

PMID- 29448156
TI  - Improved methane removal in exhaust gas from biogas upgrading process using
      immobilized methane-oxidizing bacteria.
AB  - Methane in exhaust gas from biogas upgrading process, which is a greenhouse gas,
      could cause global warming. The biofilter with immobilized methane-oxidizing
      bacteria (MOB) is a promising approach for methane removal, and the selections of
      inoculated MOB culture and support material are vital for the biofilter. In this
      work, five MOB consortia were enriched at different methane concentrations. The
      MOB-20 consortium enriched at the methane concentration of 20.0% (v/v) was then
      immobilized on sponge and two particle sizes of volcanic rock in biofilters to
      remove methane in exhaust gas from biogas upgrading process. Results showed that
      the immobilized MOB performed more admirable methane removal capacity than
      suspended cells. The immobilized MOB on sponge reached the highest methane
      removal efficiency (RE) of 35%. The rough surface, preferable hydroscopicity,
      appropriate pore size and particle size of support material might favor the MOB
      immobilization and accordingly methane removal.

PMID- 29448157
TI  - In situ surface decoration of Fe3C/Fe3O4/C nanosheets: Towards bi-functional
      activated carbons with supercapacitance and efficient dye adsorption.
AB  - This work reports a bi-functional activated porous carbon (PC) prepared from a
      biomass tofu, with excellent capacities for charge storage and adsorption of
      organic dyes, which is enabled by decorating with Fe3C/Fe3O4/C nanosheets. The in
      situ growth and self-assembly of the nanosheets on the carbon surface are
      achieved by a one-step catalytic carbonization of tofu simultaneously with FeCl3
      and ZnCl2 catalysts. Due to the high surface area and unique iron compounds
      containing and sheet-like structures, the PCs exhibit an electrochemical
      capacitance of 315 F g-1 at 0.5 A g-1 as supercapacitor electrodes, and an
      ultrahigh adsorption capacity of 918 mg g-1 for methylene blue (MB) and 868 mg g
      1 for Rhodamine B (RhB). This study provides a new perspective for understanding
      the effects of surface engineering on increasing charge storage and dye
      adsorption ability of biomass-derived PCs as well as for developing bi-functional
      PCs with novel magnetic properties.

PMID- 29448158
TI  - Despacito: the slow evolutionary changes in plant microRNAs.
AB  - MicroRNAs (miRNAs) are key regulators of gene expression. A handful of miRNAs are
      broadly conserved in land plants, while the majority are lineage specific; this
      review describes the processes by which new miRNAs are hypothesized to have
      emerged. Two major models describe miRNA origins, firstly, de novo emergence via
      inverted duplication of target gene fragments, and secondly, the expansion and
      neofunctionalization of existing miRNA families. The occasional acquisition of
      target sites by previously un-targeted genes adds further dynamism to the process
      by which miRNAs may shift roles during evolution. Additional factors guiding
      miRNA evolution include functional constraints on their length and the importance
      of precursor conservation that is observed in regions above or below the mature
      miRNA duplex; these regions represent recognition sites for components of
      biogenesis machinery and direct precursor processing. Insights into the
      mechanisms of miRNA emergence and divergence are important for understanding
      plant genome evolution and the impact of miRNA regulatory networks.

PMID- 29448159
TI  - Polyploid Arabidopsis species originated around recent glaciation maxima.
AB  - Polyploidy may provide adaptive advantages and is considered to be important for
      evolution and speciation. Polyploidy events are found throughout the evolutionary
      history of plants, however they do not seem to be uniformly distributed along the
      time axis. For example, many of the detected ancient whole-genome duplications
      (WGDs) seem to cluster around the K/Pg boundary (~66Mya), which corresponds to a
      drastic climate change event and a mass extinction. Here, we discuss more recent
      polyploidy events using Arabidopsis as the most developed plant model at the
      level of the entire genus. We review the history of the origin of allotetraploid
      species A. suecica and A. kamchatica, and tetraploid lineages of A. lyrata, A.
      arenosa and A. thaliana, and discuss potential adaptive advantages. Also, we
      highlight an association between recent glacial maxima and estimated times of
      origins of polyploidy in Arabidopsis. Such association might further support a
      link between polyploidy and environmental challenge, which has been observed now
      for different time-scales and for both ancient and recent polyploids.

PMID- 29448160
TI  - Multi-plane, multi-joint lower extremity support moments during a rapid
      deceleration task: Implications for knee loading.
AB  - The principle of lower limb support, and the contribution of hip, knee and ankle
      moments to an overall limb support strategy for an impact-like, rapid
      deceleration movement may help explain individual moment magnitude changes,
      thereby providing insight into how injury might occur or be avoided. Twenty
      subjects performed single limb, impact-like, deceleration landings at three
      different knee flexion angles in the range of 0-25, 25-50 and 50-75 degrees .
      Kinematic and kinetic measures identified hip, knee and ankle moment contribution
      to limb support moments (LSMs) in three planes. Repeated measures ANOVA compared
      LSMs and the contribution of individual joint moments at initial contact (IC) and
      50 ms after. There were no significant differences in the overall LSMs at IC in
      any plane when the deeper knee flexion landings (25-50 degrees  and 50-75 degrees
      ) were compared to the 0-25 degrees  landing position but there were significant
      changes in the 50 ms period after IC. There were greater overall extensor LSMs,
      less resistance to medial opening of the knee and decreased support against
      internal tibia rotation when landing in greater knee flexion. The role of
      individual joint moments changed rapidly in the 50 ms period after initial
      landing; and, the relative contribution of the hip and ankle moments depended on
      the degree of limb flexion at landing. Analyses of individual joint moments
      emphasized the critical role that the hip joint moments have in balancing
      potentially injurious knee moments in all three planes for all three landing
      conditions.

PMID- 29448161
TI  - How does lower limb dominance influence postural control movements during single
      leg stance?
AB  - The main purposes of the current study were to examine bilateral asymmetry in
      postural control during single-leg standing between the dominant and non-dominant
      legs using a novel analysis approach based on principal component analysis (PCA).
      It was hypothesized that the asymmetry might manifest as differences in the
      coordinative structure (control strategies), or as differences in the frequency
      or regularity of corrective interventions of the motor control system. The static
      and dynamic leg dominance of 26 active young adults (14 males and 12 females) was
      determined from their preferred leg for dynamic and for static tasks. Then
      postural movements during one-leg standing were recorded with a standard marker
      based motion capture system and analyzed by a PCA. The coordinative structure of
      postural movements was quantified using the relative variance of the principal
      movement components (PMs). Then the PMs were differentiated to obtain postural
      accelerations, from which two variables characterizing the activity (frequency
      and regularity) of the postural control system were derived. There were no
      differences in the coordinative structure, neither for dynamic nor for static leg
      preference. However, both variables characterizing asymmetries in the postural
      accelerations showed significant differences in specific PMs. Dynamic leg
      dominance yielded more and larger effects than static leg dominance. In the
      opinion of the authors, the PM-specificity of limb dominance agrees with
      principles of movement control derived from optimal feedback control theory. In
      summary, the current study suggests that leg dominance should be considered in
      clinical testing; different effects in different movement components should be
      expected; and one-leg standing should be seen as a dynamic, rather than as a
      static task.

PMID- 29448162
TI  - Cognitive-motor dual-task interference modulates mediolateral dynamic stability
      during gait in post-stroke individuals.
AB  - Gait asymmetry and dynamic balance impairments observed in post-stroke
      individuals increase their risk of fall. Moreover, walking while performing a
      cognitive task (i.e. dual-task) disturbs the control of balance in post-stroke
      individuals. Here we investigated the mediolateral dynamic stability in twenty
      two community-dwelling participants (12 post-strokes and 10 healthy controls)
      while walking in single-task (normal gait) and four different dual-tasks
      (cognitive-motor interference). Positions of the extrapolated center of mass and
      mediolateral widths of both margin of stability and base of support were
      extracted from 35 marker trajectories. Post-stroke participants presented larger
      margin of stability and base of support than controls during single-task (both p
      < 0.01), with a larger margin of stability on the non-paretic side than on the
      paretic side at ipsilateral foot-strike (p < 0.05). No significant effect of the
      dual-task was found between groups. In post-stroke participants, dual-task
      induced slight modification of the mediolateral stability strategy, as the margin
      of stability was not different between the two limbs at foot-strike, and
      significantly reduced the performance in every cognitive task. Post-stroke
      participants increased their dynamic stability in the frontal plane in single
      task by extending their base of support and mainly relying on their non-paretic
      limb. Under cognitive-motor interference (dual-task), post-stroke participants
      prioritized dynamic stability over cognitive performance to ensure a safe
      locomotion. Thus, rehabilitation programs should consider both dynamic balance
      and dual-task training, even at a chronic delay following stroke, to reduce the
      risk of fall in post-stroke individuals.

PMID- 29448163
TI  - Sperm DNA fragmentation: An early and reliable marker of air pollution.
AB  - Environmental factors could have a key role in the continuous and remarkable
      decline of sperm quality observed in the last decades. This study compared the
      seminal parameters and sperm DFI in men living in areas with different levels of
      air pollution. Results demonstrate that both steel plants workers and patients
      living in a high polluted area show a mean percentage of sperm DNA fragmentation
      above 30%, highlighting a clear sperm damage. In this work, two different
      techniques were used to measure sperm DNA damage in patients' groups, finding in
      both cases a high sperm DFI in patients living in polluted areas. We candidate
      sperm DNA fragmentation as a valuable early marker of the presence and harmful
      effects of pollution. We suggest that sperm DNA evaluation could be both an
      indicator of individual health and reproductive capacity, and a suitable datum to
      connect the surrounding environment with its effects.

PMID- 29448164
TI  - The toxicology of indium oxide.
AB  - Indium oxide (In2O3) is a technologically important semiconductor essentially
      used, doped with tin oxide, to form indium tin oxide (ITO). It is poorly soluble
      in all so far tested physiologic media. After repeated inhalation, In2O3
      particles accumulate in the lungs. Their mobilization can cause significant
      systemic exposure over long periods of time. An increasing number of cases of
      severe lung effects (characterized by pulmonary alveolar proteinosis, emphysema
      and/or interstitial fibrosis) in workers of the ITO industry warrants a review of
      the toxicological hazards also of In2O3. The database on acute and chronic
      toxicity/carcinogenicity/genotoxicity/reproductive toxicity as well skin/eye
      irritation and sensitization is very limited or even lacking. Short-term and
      subchronic inhalation studies in rats and mice revealed persistent alveolar
      proteinosis, inflammation and early indicators of fibrosis in the lungs down to
      concentrations of 1 mg/m3. Epidemiological and medical surveillance studies,
      serum/blood indium levels in workers as well as data on the exposure to airborne
      indium concentrations indicate a need for measures to reduce exposure at In2O3
      workplaces.

PMID- 29448165
TI  - 90Y radioembolization dosimetry using a simple semi-quantitative method in
      intrahepatic cholangiocarcinoma: Glass versus resin microspheres.
AB  - INTRODUCTION: There are two different types of 90Y Microspheres, glass and resin,
      in the market for 90Y radioembolization (90Y-RE). This study aimed to investigate
      the dose of radiation delivered through glass vs. resin-based 90Y-RE to
      intrahepatic cholangiocarcinoma (ICC). METHODS: In this retrospective study, 10
      patients with ICC underwent 90Y-RE, five underwent glass (Glass group) and other
      5 resin (Resin group) microspheres. Technetium-99m macro-aggregated albumin (Tc
      99m MAA) shunt study was performed two weeks before 90Y-RE. Within 2 h from 90Y
      RE, Bremsstrahlung SPECT/CT was obtained. Regions of interest (ROIs) were
      segmented around the targeted tumor and the liver. Tumor and liver volumes,
      corresponding radioactive counts, and tumor to liver count ratio were calculated
      using MIM software and compared between Glass and Resin groups. RESULTS: Mean
      hepatopulmonary shunt fraction was 7.1 vs. 6.2% for the Glass and Resin groups (p
      = 0.83), with no extrahepatic activity. There was no difference in the activity
      and tumor uptake of administered Tc-99m MAA between both groups (p = 0.71 and p =
      0.63). Mean administered activity of 90Y in the Glass group was higher than the
      Resin group (73.2 +/- 24.3 vs. 44.5 +/- 18.2 mCi, p < 0.001). The tumor 90Y
      uptake was significantly higher in the Glass group compared to the Resin group
      (41.3% vs. 33.5%, p < 0.001), corresponding to the mean tumor dose of 205.7 +/-
      19.7 vs. 128.9 +/- 10.6 Gy, respectively (p < 0.001). The tumor to normal liver
      parenchyma 90Y dose ratio was significantly higher in the Glass group compared to
      the Resin group, 4.9 +/- 0.7 versus 2.4 +/- 0.3 respectably (p < 0.001).
      CONCLUSIONS: Both 90Y glass and resin-based microsphere 90Y-RE are feasible and
      safe in patients with ICC, while 90Y glass microsphere delivers higher dose of
      90Y to the targeted tumors. ADVANCES IN KNOWLEDGE: While both 90Y glass and resin
      based microsphere yttrium-90 radioembolization are feasible and safe treatment
      options for in patients with intrahepatic cholangiocarcinoma, 90Y glass
      microsphere delivers higher dose of 90Y to the targeted tumors. IMPLICATIONS FOR
      PATIENT CARE: Both of 90Y glass and resin-based microsphere can be safely and
      feasibly used for treatment of intrahepatic cholangiocarcinoma, difference in
      dose of 90Y delivered to the targeted tumors should be clinically considered
      while choosing the microsphere type.

PMID- 29448166
TI  - Insights from population-based analyses of plasma lipids across the allele
      frequency spectrum.
AB  - Plasma lipid levels are heritable quantitative risk factors and therapeutic
      targets for cardiovascular disease. Plasma lipids have been a model for
      translating genetic observations across the allele frequency spectrum to unique
      biological and therapeutic insights. Most large studies to date predominately
      comprised of individuals of European ancestry. This review focuses on
      contemporary evidence from 2016 to 2017 looking at the effect of genetic variants
      on plasma lipid levels across the allele frequency spectrum with incrementally
      larger sample sizes and the contribution of non-European ancestry studies to the
      genetic etiology of plasma lipid levels. To date, over 250 loci have been
      associated with plasma lipid levels and several of these loci have additional
      evidence of association with rare coding variants providing evidence for causal
      genes at the locus.

PMID- 29448167
TI  - Development of graphite carbon nitride based fluorescent immune sensor for
      detection of alpha fetoprotein.
AB  - A novel fluorescent immunosensor for determination of alpha fetoprotein (AFP) in
      serum samples has been developed based on the nano graphite carbon nitride (g
      C3N4) as fluorophore and immunomagnetic beads (MBs) as separation material. The
      bulk g-C3N4 was obtained by thermal polymerization of melamine, and then
      carboxylated and exfoliated to acquire the carboxylated nano g-C3N4 (c-n-g-C3N4),
      which has been characterized and the results showed that it had excellent
      fluorescent properties. The antibodies of AFP (Ab1, Ab2) were conjugated to the
      MBs and the c-n-g-C3N4, respectively. In assay of AFP detection, the magnetic
      part of the immunosensor, MBs-Ab1, would form the sandwich type complex with the
      signal part of the sensor, c-n-g-C3N4-Ab2. The developed immunosensor could
      simplify the process of separation due to the MBs. The results illustrated that
      proposed approach held a good linearity between the fluorescence intensity of the
      sensor and the AFP concentration ranging from 5-600ng/mL with the limit of
      detection as low as 0.43ng/mL, and its spiking recoveries ranged from 98.2% to
      105.9% with RSD from 2.1% to 3.5%. The fabricated fluorescent immunosensor
      possesses the merits of good sensitivity, excellent selectivity, high
      biocompatibility and low cost, and the results provide a novel clue to develop
      immunosensor for determination of the biomarkers in complex matrices.

PMID- 29448168
TI  - Simultaneous determination of Magnolol and Honokiol by amino acid ionic liquid
      synchronous fluorescence spectrometry.
AB  - A novel method based on amino acid ionic liquids (AAILs) as an additive
      synchronous fluorescence spectrometry is proposed for simultaneous determination
      of magnolol (MN) and honokiol (HN) in traditional Chinese medicine Houpu. The
      overlapping fluorescence spectrum of MN and HN could be completely separated in
      the AAILs medium. Experiment parameters (the type and concentration of AAILs, pH
      values and temperature) were discussed. The detection limits of MN and HN reached
      1.46ng/mL, 0.92ng/mL and the recovery rates ranged from 98.6%-100.7%, 99.7%
      100.6%, respectively. This methods was successfully employed for simultaneously
      determination of MN and HN in real samples. No significant differences could be
      found in the results of this method and the pharmacopoeia of People's Republic of
      China 2015 (Ch.P.2015). The experiment mechanisms were discussed by the Gaussian
      simulation and fluorescence quantum yield.

PMID- 29448169
TI  - Molecular spectroscopic features of protein in newly developed chickpea:
      Relationship with protein chemical profile and metabolism in the rumen and
      intestine of dairy cows.
AB  - The first aim of this study was to investigate the nutritional value of crude
      protein (CP) in CDC [Crop Development Centre (CDC), University of Saskatchewan]
      chickpea varieties (Frontier kabuli and Corinne desi) in comparison with a CDC
      barley variety in terms of: 1) CP chemical profile and subfractions; (2) in situ
      rumen degradation kinetics and intestinal digestibility of CP; 2) metabolizable
      protein (MP) supply to dairy cows; and (3) protein molecular structure
      characteristics using advanced molecular spectroscopy. The second aim was to
      quantify the relationship between protein molecular spectral characteristics and
      CP subfractions, in situ rumen CP degradation characteristics, intestinal
      digestibility of CP, and MP supply to dairy cows. Samples (n=4) of each variety,
      from two consecutive years were analyzed. Chickpeas had higher (P<0.01) CP
      content (21.71-22.11 vs 12.96% DM), with higher (P<0.05) soluble CP subfraction
      (59.07-70.27 vs 26.18% CP), and in situ soluble (23.44-25.85 vs 1.30% CP) and
      rumen degradable (RDP; 72.23-72.57 vs 58.48% CP) fractions than barley. The
      potentially slowly rumen degradable (D; 74.14-76.56 vs 93.31% CP) and
      undegradable (RUP; 27.43-27.66 vs 41.52% CP) fractions were lower (P<0.01) in the
      chickpeas than barley. The effective degradability ratio of N to organic matter
      (OM) (36.07-38.44gN/kg OM) of the chickpeas was higher than the optimal for
      achieving optimum microbial CP (MCP) synthesis. The truly digested MCP (64.94
      66.43 vs. 41.43g/kg DM); MP (81.10-83.67 vs 61.0g/kg DM) feed milk value (1.64
      1.70 vs 1.24) was higher in the chickpeas than barley grain. The chickpeas had
      higher (P<0.05) amide I and II peaks area and height, and alpha-helix and beta
      sheet peaks height than barley. Multivariate analysis showed that protein
      molecular spectral data of chickpeas can be distinguished from the barley. The
      two chickpeas did not differ in CP content, and any of the measured in situ
      degradation and molecular spectral characteristics of protein. The content of RUP
      was positively (r=0.94, P<0.01) and that of RDP was negatively (r=-0.94, P<0.01)
      correlated with amide I/II area ratio. The regression analysis showed that the
      content of CP (R2=0.91) D-fraction (R2=0.82), RDP (R2=0.77), RUP (R2=0.77), TDP
      (R2=0.98), MP (R2=0.80), and FMV (R2=0.80) can be predicted from amide II peak
      height. Despite extensive ruminal degradation, chickpea is a good source of MP
      for dairy cows, and molecular spectroscopy can be used to rapidly characterize
      feed protein molecular structures and predict their digestibility and nutritive
      value.

PMID- 29448170
TI  - Study of interaction between ionic liquids and orange G in aqueous solution with
      UV-vis spectroscopy and conductivity meter.
AB  - The interactions between Orange G (OG) with three kinds of ionic liquid
      surfactants (C10mimBF4, C12mimBF4, C16mimBF4) and CTAB were studied with UV-Vis
      spectra and conductivity measurements. The systematic changes in UV-Vis spectra
      with an increase of carbon-chain length may be observed in presence of OG. They
      correspond to CMC of every system, respectively, and the CMCs of four systems
      have exhibit the decrease of CMCs compared to pure surfactant. The binding
      constants are calculated from the results of conductivity measurements in the
      order of C16mimBF4>CTAB>C12mimBF4>C10mimBF4. Furthermore, system behaviors
      presented significant association of complex formation and micelles formation,
      i.e. the change in UV-Vis spectra before and after the formation of micelles in
      mixed systems. In addition, Fourier-transform infrared (FT-IR) spectroscopy and
      1H NMR analysis further confirmed that the complexes are formed by hydrogen bond
      and van der Waal force. These findings could provide scientific guidance for
      extraction and separation of dyes.

PMID- 29448171
TI  - Evaluation of the effect of polymorphism on G-quadruplex-ligand interaction by
      means of spectroscopic and chromatographic techniques.
AB  - Guanine-rich sequences may fold into highly ordered structures known as G
      quadruplexes. Apart from the monomeric G-quadruplex, these sequences may form
      multimeric structures that are not usually considered when studying interaction
      with ligands. This work studies the interaction of a ligand, crystal violet, with
      three guanine-rich DNA sequences with the capacity to form multimeric structures.
      These sequences correspond to short stretches found near the promoter regions of
      c-kit and SMARCA4 genes. Instrumental techniques (circular dichroism, molecular
      fluorescence, size-exclusion chromatography and electrospray ionization mass
      spectrometry) and multivariate data analysis were used for this purpose. The
      polymorphism of G-quadruplexes was characterized prior to the interaction
      studies. The ligand was shown to interact preferentially with the monomeric G
      quadruplex; the binding stoichiometry was 1:1 and the binding constant was in the
      order of 105M-1 for all three sequences. The results highlight the importance of
      DNA treatment prior to interaction studies.

PMID- 29448172
TI  - Analysis of quetiapine in human plasma using fluorescence spectroscopy.
AB  - A simple and sensitive spectrofluorimetric method has been development for the
      assurance of quetiapine fumarate (QTF). The proposed method was utilized for
      measuring the fluorescence intensity of the yellow fluorescent product at 510nm
      (lambdaex 470nm). The fluorescent product has resulted from the nucleophilic
      substitution reaction of QTF with 4-chloro-7-nitrobenzofurazane (NBD-Cl) in
      Mcllvaine buffer (pH7.0). The diverse variables influencing the development of
      the reaction product were deliberately changed and optimized. The linear
      concentration range of the proposed method was of 0.2-2.0MUgml-1.The limits of
      detection and quantitation were 0.05 and 0.17MUgml-1, respectively. The proposed
      method was applied for the assurance of QTF in its tablets without interference
      from basic excipients. In addition, the proposed method was used for in vitro
      analysis of the QTF in spiked human plasma, the percent mean recovery was (n=3)
      98.82+/-1.484%.

PMID- 29448173
TI  - Enhancement of UVB-induced DNA damage repair after a chronic low-dose UVB pre
      stimulation.
AB  - Absorption of solar ultraviolet (UV) radiation by DNA leads to the formation of
      the highly mutagenic cyclobutane pyrimidine dimer (CPD). The mutagenicity of CPD
      is caused, in part, by the fact that their recognition and repair by the
      nucleotide excision repair (NER) pathway is challenging and slow. It has been
      previously shown that a pre-stimulation with genotoxic agents improve NER
      efficiency of CPD, indicating a potential adaptive response of this repair
      pathway. We have pre-treated human dermal fibroblasts with repeated subletal low
      doses of UVB (chronic low-dose of UVB; CLUV) to determine whether it could
      enhance NER capacity to repair CPD. Our results show that CLUV pre-treatment
      greatly enhances CPD repair but have little effect on the repair of another UV
      induced bypirimidine photoproduct, the pyrimidine (6-4) pyrimidone photoproducts
      (6-4 PP). We have determined that the CLUV treatment activates p53 and we found
      an increase of DDB2 and XPC gene expression. This is consistent with an
      increasing level of NER recognition proteins, DDB2 and XPC, we found concentrated
      at the chromatin. This study represents the first demonstration that chronic UVB
      exposure can stimulate NER pathway. Altogether, these results shed light on the
      potential adaptability of the NER by chronic UVB irradiation and the mechanisms
      involved.

PMID- 29448174
TI  - Extracellular vesicles - new players in cell-cell communication in aquatic
      environments.
AB  - Communication between microorganisms in aquatic environments can influence
      ecosystem function and determine the structure and composition of microbial
      populations. This microbial cross talk can be mediated by excretion of
      specialized metabolites or extracellular vesicles (EVs). Recently it has become
      apparent that cells across all domains of life produce EVs that may convey
      specific targeted signals that can modulate cell fate, morphology and
      susceptibility to viruses. The vast majority of knowledge about EVs is derived
      from studies of mammalian tissues, parasitic host-pathogen interactions and model
      bacterial systems. Very little is known about the role of EVs in aquatic
      environments, although they have potential to influence community structure and
      trophic-level interactions. We propose functions and ecological implications of
      communication via EVs in aquatic microbial ecosystems.

PMID- 29448175
TI  - Metals in mangrove ecosystems and associated biota: A global perspective.
AB  - Mangrove forests prevalent along the intertidal regions of tropical and sub
      tropical coastlines are inimitable and dynamic ecosystems. They protect and
      stabilize coastal areas from deleterious consequences of natural disasters such
      as hurricanes and tsunamis. Although there are reviews on ecological aspects,
      industrial uses of mangrove-associated microorganisms and occurrence of
      pollutants in a region-specific manner, there is no exclusive review detailing
      the incidence of metals in mangrove sediments and associated biota in these
      ecosystems on a global level. In this review, mangrove forests have been
      classified in a continent-wise manner. Most of the investigations detail the
      distribution of metals such as zinc, chromium, arsenic, copper, cobalt,
      manganese, nickel, lead and mercury although in some cases levels of vanadium,
      strontium, zirconium and uranium have also been studied. Seasonal, tidal, marine,
      riverine, and terrestrial components are seen to influence occurrence,
      speciation, bioavailability and fate of metals in these ecosystems. In most of
      the cases, associated plants and animals also accumulate metals to different
      extents and are of ecotoxicological relevance. Levels of metals vary in a region
      specific manner and there is disparity in the pollution status of different
      mangrove areas. Protecting these vulnerable ecosystems from metal pollutants is
      important from environmental safety point of view.

PMID- 29448176
TI  - Mechanisms of phloem loading.
AB  - The complex form of higher plants requires continuous, balanced transport of
      nutrients in the phloem. The initial step of transferring sugars, amino acids,
      and other materials from photosynthetic cells to the conducting sieve tubes is
      known as phloem loading. Three phloem loading mechanisms have been described. The
      first involves release of sucrose into the apoplast and subsequent retrieval by
      the phloem. The initial release step in this process is now known to be mediated
      by a new class of transporters, the SWEET proteins. In the other two loading
      mechanisms, polymer trapping and diffusion, sucrose passes into the phloem
      through cytoplasmic channels, the plasmodesmata. Recent models have shed
      additional light on these mechanisms and their ability to sustain the growth of
      even the tallest trees.

PMID- 29448177
TI  - Drought impacts on phloem transport.
AB  - Drought impacts on phloem transport have attracted attention only recently,
      despite the well-established, and empirically verified theories on drought
      impacts on water transport in plants in general. This is because studying phloem
      transport is challenging. Phloem tissue is relatively small and delicate, and it
      has often been assumed not to be impacted by drought, or having insignificant
      impact on plant function or survival compared to the xylem. New evidence,
      however, suggests that drought responses of the phloem might hold the key for
      predicting plant survival time during drought or revival capacity after drought.
      This review summarizes current theories and empirical evidence on how drought
      might impact phloem transport, and evaluates these findings in relation to plant
      survival during drought.

PMID- 29448178
TI  - Modification of the association between antipsychotic treatment response and
      childhood adversity by MMP9 gene variants in a first-episode schizophrenia
      cohort.
AB  - Antipsychotics remain the most effective, and wide used option for ameliorating
      the symptoms of schizophrenia. However, inter-individual differences in treatment
      outcome are vast and suggest a role for genetic and environmental factors in
      affording favourable outcomes. A notable epigenetic relationship which has gained
      considerable traction in recent literature is the way in which the severity of
      childhood trauma can modify associations seen between genetic variation and
      antipsychotic treatment response. A potential mechanism of action which may
      facilitate this relationship is synaptic plasticity. This study investigated the
      role of variants in matrix metallopeptidase 9 (MMP9), a gene involved in synaptic
      plasticity, with treatment outcome considering the severity of childhood trauma
      as an interacting variable. The cohort comprised South African first episode
      schizophrenia patients treated with a single injectable antipsychotic,
      flupenthixol decanoate, monitored over 12 months. Relationships between novel and
      previously described variants, and haplotypes, with antipsychotic treatment
      response were found to be modified when considering childhood trauma as an
      interacting variable. This study provides the first evidence for the involvement
      of polymorphisms within MMP9 and the severity of childhood trauma in
      antipsychotic treatment response, and warrants further investigation into the
      role gene-environment interactions may play in the betterment of antipsychotic
      treatment strategies.

PMID- 29448179
TI  - Elevated neutrophil to lymphocyte ratio in non-affective psychotic adolescent
      inpatients: Evidence for early association between inflammation and psychosis.
AB  - Accumulating data suggest an association between inflammation and schizophrenia
      and related psychosis. While several studies have established this immune
      psychosis association in adult schizophrenia patients, there is very limited data
      associating inflammation with acute psychosis in children and adolescents. The
      ratio between neutrophils and lymphocyte, computed from routine blood counts, has
      been shown to correlate with traditional markers of inflammation, and is
      therefore considered a proxy-marker for inflammation. Here we report elevated
      neutrophil to lymphocyte ratio and total leukocyte count in psychotic adolescent
      inpatients (n = 81, mean age 14.7 years, 52% males) compared to non-psychotic
      adolescent inpatient (n = 285, mean age 15.9 years, 58% males), in a population
      of adolescent inpatients with no affective symptomatology. The elevated
      neutrophil to lymphocyte ratio remained significant after controlling for
      confounders such as age, BMI, smoking and antipsychotic medication. In a subset
      of psychotic adolescent inpatients (n = 20, mean duration between blood test 157
      days), we found significant decrease in neutrophil to lymphocyte ratio at
      clinical remission compared with the acute psychotic state. The results suggest
      that psychosis is associated with peripheral markers of inflammation early in the
      course of psychiatric pathology, and that inflammation may represent a state that
      accompanies psychosis and decreases during clinical remission.

PMID- 29448180
TI  - Feasibility of four wastes to remove heavy metals from contaminated soils.
AB  - Soil washing is one of the permanent techniques to remove heavy metals, and
      washing agent is a key influence factor for this technique, but there is still
      lack of high-efficiency, eco-friendly, and inexpensive agents. In this study,
      four wastes including pineapple peel (PP), soybean straw (SS), broad bean straw
      (BBS) and tea residue (TR) were employed to remove cadmium (Cd), lead (Pb) and
      zinc (Zn) in contaminated soils. The Fourier transform infrared spectroscopy
      (FTIR) analysis indicated that hydroxyl, carboxyl, amine, carbonyl and amide
      groups were involved in the interaction with metal ions by complexation or ion
      exchange. We then investigated the influences of various conditions including
      washing solution concentration, pH, and washing time. The metal removal
      efficiencies with these agents increased as the concentration augmented from 5 to
      80 g L-1, decreased or presented an asymmetric V-shaped curve with increasing pH
      from 2.5 to 7.5, and fit intraparticle diffusion or Elovich model with washing
      time increasing. PP has the highest removals for Cd (90.1%), Pb (18.6%), and Zn
      (15.2%) in soil A, and 85.8, 24.8, and 69.4% in soil B, respectively. The
      relatively high metal removal was mainly attributed to effective removal of the
      exchangeable and acid soluble fractions. Moreover, single washing not only
      lowered the potential ecological risk of the heavy metals, but moderated the
      effects on soil chemical properties. Therefore, PP was a feasible washing agent
      to remediate soils contaminated by heavy metals.

PMID- 29448181
TI  - Effect of beach management policies on recreational water quality.
AB  - When beach water monitoring programs identify poor water quality, the causes are
      frequently unknown. We hypothesize that management policies play an important
      role in the frequency of fecal indicator bacteria (FIB) exceedances (enterococci
      and fecal coliform) at recreational beaches. To test this hypothesis we
      implemented an innovative approach utilizing large amounts of monitoring data (n
      > 150,000 measurements per FIB) to determine associations between the frequency
      of contaminant exceedances and beach management practices. The large FIB database
      was augmented with results from a survey designed to assess management policies
      for 316 beaches throughout the state of Florida. The FIB and survey data were
      analyzed using t-tests, ANOVA, factor analysis, and linear regression. Results
      show that beach geomorphology (beach type) was highly associated with exceedance
      of regulatory standards. Low enterococci exceedances were associated with open
      coast beaches (n = 211) that have sparse human densities, no homeless
      populations, low densities of dogs and birds, bird management policies, low
      densities of seaweed, beach renourishment, charge access fees, employ lifeguards,
      without nearby marinas, and those that manage storm water. Factor analysis and a
      linear regression confirmed beach type as the predominant factor with secondary
      influences from grooming activities (including seaweed densities and beach
      renourishment) and beach access (including charging fees, employing lifeguards,
      and without nearby marinas). Our results were observable primarily because of the
      very large public FIB database available for analyses; similar approaches can be
      adopted at other beaches. The findings of this research have important policy
      implications because the selected beach management practices that were associated
      with low levels of FIB can be implemented in other parts of the US and around the
      world to improve recreational beach water quality.

PMID- 29448182
TI  - Enhanced alumina recovery from secondary aluminum dross for high purity
      nanostructured gamma-alumina powder production: Kinetic study.
AB  - The numerous ecological problems caused by the accumulation of secondary aluminum
      dross (SAD) as a hazardous waste generated in aluminum castings have necessitated
      a need for a sustainable recycling solution. This study proposes a novel and
      green leaching-based process for recovery of nano-alumina as a highly valuable
      material from SAD. The leaching phase was performed at atmospheric pressure and
      low temperature. To obtain optimum conditions for the recovery process, the
      dissolution kinetics and mechanism of SAD in hydrochloric acid were initially
      studied under a given liquid-to-solid ratio of 20 ml/g, various reaction
      temperatures and times. It was found that the dissolution of SAD in HCl was
      controlled by layer diffusion with an apparent activation energy of around 10.49
      kJ/mol. Alumina in the form of a high purity nanostructured powder from SAD was
      then recovered under optimum conditions of 85  degrees C, acid concentration of 5
      mol/l, and reaction time of 120 min by the proposed process. Characterization of
      nano-alumina was performed using X-ray diffractometry (XRD), Fourier transform
      infrared (FTIR) spectroscopy, field emission scanning electron microscopy
      (FESEM), energy-dispersive X-ray spectroscopy (EDAX), and transmission electron
      microscopy (TEM) techniques. The results revealed that the as-produced alumina
      had a nano-crystalline structure, having the crystal size of 15.90 nm and
      consisting mainly of gamma phase. The microstructural studies disclosed the
      aggregations of rounded-corner shaped particles. Also, wet chemical analysis
      showed a purity of more than 98% for the produced alumina.

PMID- 29448183
TI  - Change in metals and arsenic distribution in soil and their bioavailability
      beside old tailing ponds.
AB  - The objectives of this study were to determine the metals and arsenic transfer
      from mining ponds to agricultural and forest soils, and identify the dynamic of
      metal(loid)s in the soil-plant system for a native plant species (Ballota
      hirsuta) in two old mining districts: La Union and Mazarron (Spain). Soils and
      plants from mining ponds and natural and agricultural areas were collected and
      analyzed for soil properties, and chemical partitioning of Cd, Co, Cr, Cu, Fe,
      Mn, Ni, Pb, Zn and As. Results showed that mine, forest and agricultural soils
      were contaminated by As, Cd, Cu, Pb, and Zn. Chemical partitioning revealed
      higher mobility of metals in mining ponds than natural and agricultural soils
      except for Fe and As which were mostly bound to soil matrix due to the
      mineralogical compositions of soils. The accumulation of metal(loid)s in B.
      hirsuta in La Union decreased as Fe > As > Cr > Ni > Cu > Zn > Cd > Mn > Co > Pb
      while in Mazarron was As > Fe > Cr > Pb > Cu > Ni > Co > Mn > Zn > Cd, showing
      that B. hirsuta has high ability to bio-accumulate Fe, As, Cr, Cu and Ni; and Pb
      (in Mazarron), transferring a significant concentration of theses metal(loid)s,
      except Pb, to edible parts without exceeding the toxicity limits for animals.
      Therefore, B. hirsuta could be useful as phytoextractor species for Cr, Cu, As
      and Ni, while it can be used as phytostabilizer species for Zn, Co, Pb and Cd.

PMID- 29448184
TI  - Spontaneous alveolar bone loss after 4NQO exposure in Wistar rats.
AB  - OBJECTIVE: This study evaluated the effect of an experimental carcinogenic, 4
      Nitroquinoline 1-oxide (4NQO), in the spontaneous alveolar bone loss (ABL) in an
      animal model. DESIGN: Twenty-two male Wistar rats were included in this study.
      They were randomly divided into two groups: the control group (n = 10) received
      food and water ad libitum, and the test group (n = 12) receive the same food;
      however, 25 ppm of 4NQO was diluted in the drinking water. All animals were
      euthanized after 20 weeks, and the tongues were removed and analyzed
      macroscopically to determine the presence of oral mucosal lesions. All specimens
      were paraffin-embedded and histological sections were obtained. The microscopic
      analysis was based on routine procedure (haematoxylin and eosin stain). The
      analysis of spontaneous ABL was performed by a calibrated examiner using
      standardized photographs and imaging software. Differences in spontaneous ABL
      were assessed among the three resulting groups: control, 4NQO with oral squamous
      cell carcinoma (OSCC), and 4NQO without OSCC. RESULTS: In the 4NQO-treated group,
      nine animals developed OSCC. The animals in the 4NQO with OSCC group presented
      significantly more spontaneous ABL (0.65 +/- 0.21 mm) than the control group
      (0.34 +/- 0.05) (p < 0.001). The animals in the 4NQO without OSCC group showed a
      mean spontaneous ABL of 0.47 +/- 0.13 mm, which was not statistically significant
      different when compared to the control group (p = 0.096). CONCLUSIONS: It was
      concluded that the presence of OSCC enhanced spontaneous ABL in Wistar rats when
      compared to control animals. Additionally, it was shown that, solely,
      administration of 4NQO may not be considered responsible for alveolar bone
      destruction.

PMID- 29448185
TI  - The effect of parental style on bullying and cyber bullying behaviors and the
      mediating role of peer attachment relationships: A longitudinal study.
AB  - The purpose of the present study was the examination of the longitudinal effect
      of parental style on short-term changes in conventional and cyber forms of
      bullying/victimization, and the investigation of the mediating role of peer
      attachment relationships on this effect. The participants were 861 children and
      adolescents (52% girls, Mage = 11.72 years) attending Cyprus public institutions.
      Students provided information during three measurement points. There was a six
      and a 12 week interval among the three measurement points, respectively. The
      findings of the study indicated that parenting seems to be a significant
      predictor of all forms of bullying/victimization, conventional and cyber, in
      early adolescents, even when accounting for bullying/victimization levels
      eighteen weeks back. More importantly, results showed that the effect of parental
      style on bullying forms was mediated by peer attachment relationships. Results
      are discussed in the light of theoretical and practical implications.

PMID- 29448186
TI  - Cognitive development in children of adolescent mothers: The impact of
      socioeconomic risk and maternal sensitivity.
AB  - BACKGROUND: Adolescent motherhood is accompanied by a constellation of risk
      factors that translate into developmental risk for the off-spring. Socioeconomic
      risk that is associated with adolescent motherhood as well as maternal
      interactive behaviors may contribute to the impact of adolescent motherhood on
      children's developmental outcome. OBJECTIVE: Therefore, the aim of the current
      study was to investigate differences in children's cognitive development between
      children of adolescent and adult mothers in their first two years of life and to
      examine whether socioeconomic risk (e.g. such as educational and financial
      problems) and/or maternal sensitivity mediate developmental differences between
      children of adolescent and adult mothers. METHODS: Adolescent mothers (<21 years;
      N = 64) and adult mothers (>25 years; N = 34) and their infants were included in
      the current study. Child cognitive development and maternal sensitivity were
      assessed at three different time points (T1: mean child age 5.26 months; T2: mean
      child age 14.69 months; T3: mean child age 21.16 months). RESULTS: Children of
      adult mothers showed better cognitive performance at T3 compared to children of
      adolescent mothers but not at T1 and T2. A multiple mediation model including
      socioeconomic risk and maternal sensitivity as serial mediators demonstrated that
      the effect of adolescent motherhood on cognitive development was mediated in a
      causal effect chain with socioeconomic risk negatively affecting maternal
      sensitivity and maternal sensitivity affecting children's cognitive development.
      DISCUSSION: The present findings demonstrate that maternal interactive behaviors
      are not only a simple predictor of cognitive development but may also act as a
      mediator of the association between more distal variables such as socioeconomic
      risk and cognitive development in adolescent mothers. This supports the need to
      promote prevention and intervention programs for adolescent mothers during the
      early postpartum period to reduce socioeconomic problems and enhance maternal
      interactive behaviors.

PMID- 29448187
TI  - Development of the Drooling Infants and Preschoolers Scale (DRIPS) and reference
      charts for monitoring saliva control in children aged 0-4 years.
AB  - OBJECTIVES: To develop and validate a parent questionnaire to quantify drooling
      severity and frequency in young children (the Drooling Infants and Preschoolers
      Scale - the DRIPS). To investigate development of saliva control in typically
      developing young children in the age of 0-4 years. To construct sex-specific
      reference charts presenting percentile curves for drooling plotted for age to
      monitor the development of saliva control in infancy and preschool age. STUDY
      DESIGN: The DRIPS was developed consisting of 20 items to identify severity and
      frequency of drooling during meaningful daily activities. Factor analysis was
      performed to test construct validity. A piecewise logistic regression was
      followed by a piecewise linear regression to construct sex-specific reference
      charts. RESULTS: We obtained 652 completed questionnaires from parents of
      typically developing children. The factor analysis revealed four discriminating
      components: drooling during Activities, Feeding, Non nutritive sucking, and
      Sleep. To illustrate the development of saliva control, eight sex-specific
      reference curves were constructed to plot the scores of the DRIPS by age group,
      at the 15th, 50th, 85th and 97th percentile. About 3-15% of the preschoolers in
      our cohort did not acquire full saliva control at the age of 4 years.
      CONCLUSIONS: With the DRIPS it is possible to validly compare and visualize the
      development of saliva control in an individual infant or preschooler and allow
      clinicians to timely initiate individually targeted interventions if children
      outperform.

PMID- 29448188
TI  - Genotype, phenotype and in silico pathogenicity analysis of HEXB mutations: Panel
      based sequencing for differential diagnosis of gangliosidosis.
AB  - OBJECTIVES: Gangliosidosis is an inherited metabolic disorder causing
      neurodegeneration and motor regression. Preventive diagnosis is the first choice
      for the affected families due to lack of straightforward therapy. Genetic studies
      could confirm the diagnosis and help families for carrier screening and prenatal
      diagnosis. An update of HEXB gene variants concerning genotype, phenotype and in
      silico analysis are presented. PATIENTS AND METHODS: Panel based next generation
      sequencing and direct sequencing of four cases were performed to confirm the
      clinical diagnosis and for reproductive planning. Bioinformatic analyses of the
      HEXB mutation database were also performed. RESULTS: Direct sequencing of HEXA
      and HEXB genes showed recurrent homozygous variants at c.509G>A (p.Arg170Gln) and
      c.850C>T (p.Arg284Ter), respectively. A novel variant at c.416T>A (p.Leu139Gln)
      was identified in the GLB1 gene. Panel based next generation sequencing was
      performed for an undiagnosed patient which showed a novel mutation at c.1602C>A
      (p.Cys534Ter) of HEXB gene. Bioinformatic analysis of the HEXB mutation database
      showed 97% consistency of in silico genotype analysis with the phenotype.
      Bioinformatic analysis of the novel variants predicted to be disease causing. In
      silico structural and functional analysis of the novel variants showed structural
      effect of HEXB and functional effect of GLB1 variants which would provide fast
      analysis of novel variants. CONCLUSIONS: Panel based studies could be performed
      for overlapping symptomatic patients. Consequently, genetic testing would help
      affected families for patients' management, carrier detection, and family
      planning's.

PMID- 29448189
TI  - 3-(E)-Styryl-2H-chromene derivatives as potent and selective monoamine oxidase B
      inhibitors.
AB  - A series of novel 3-(E)-styryl-2H-chromene derivatives were synthesized and their
      monoamine oxidase (MAO) A and B inhibitory activities were evaluated. All
      compounds exhibited no inhibitory activity towards MAO-A at 10 MUM whereas
      compounds 1-5, 7, 9, 11-13, 15 and 16 showed strong inhibitory activity towards
      MAO-B at this concentration. Of these, compound 3, which contains fluorine at R3,
      showed the highest activity (IC50 = 10 nM), and is about 22-fold more potent than
      pargyline (used as a positive control). Quantitative structure-activity
      relationship (QSAR) analyses of 3-(E)-styryl-2H-chromene derivatives were
      conducted using Molecular Operating Environment (MOE). QSAR analyses of 3-(E)
      styryl-2H-chromene derivatives with pIC50 values for MAO-B demonstrated that 140
      descriptors showed significant correlations. The strongly correlated descriptors
      indicated that properties such as molecular shape, size, and hydrophobicity, as
      well as the functional groups, of 3-(E)-styryl-2H-chromene derivatives are
      important for their inhibitory activity. This is the first report identifying 3
      (E)-styryl-2H-chromene derivatives as potent and selective MAO-B inhibitors.
      These results suggest that the 3-(E)-styryl-2H-chromene structure may be a useful
      scaffold for the design and development of novel monoamine oxidase inhibitors.

PMID- 29448190
TI  - Gene expression in Pseudomonas aeruginosa exposed to hydroxyl-radicals.
AB  - Recent studies have shown the efficiency of hydroxyl radicals generated via
      ultraviolet (UV)-based advanced oxidation processes (AOPs) combined with hydrogen
      peroxide (UV/H2O2) as a treatment process in water. The effects of AOP treatments
      on bacterial gene expression was examined using Pseudomonas aeruginosa strain
      PAO1 as a model-organism bacterium. Many bacterial genes are not expressed all
      the time, but their expression is regulated. The regulation is at the beginning
      of the gene, in a genetic region called "promoter" and affects the level of
      transcription (synthesis of messenger RNA) and translation (synthesis of
      protein). The level of expression of the regulated genes can change as a function
      of environmental conditions, and they can be expressed more (induced,
      upregulated) or less (downregulated). Exposure of strain PAO1 to UV/H2O2
      treatment resulted in a major change in gene expression, including elevated
      expression of several genes. One interesting gene is PA3237, which was
      significantly upregulated under UV/H2O2 as compared to UV or H2O2 treatments
      alone. The induction of this gene is probably due to formation of radicals, as it
      is abolished in the presence of the radical scavenger tert-butanol (TBA) and is
      seen even when the bacteria are added after the treatment (post-treatment
      exposure). Upregulation of the PA3237 promoter could also be detected using a
      reporter gene, suggesting the use of such genetic constructs to develop
      biosensors for monitoring AOPs in water-treatment plants. Currently biosensors
      for AOPs do not exist, consequently impairing the ability to monitor these
      processes on-line according to radical exposure in natural waters.

PMID- 29448191
TI  - Novel arrangement for an electro-Fenton reactor that does not require addition of
      iron, acid and a final neutralization stage. Towards the development of a cost
      effective technology for the treatment of wastewater.
AB  - A novel arrangement for an electro-Fenton reactor aimed to treat neutral
      wastewater is presented. The arrangement consists on three-compartments in
      series, two of them packed with a cation exchange resin and one positioned
      between these, containing a polarized activated carbon column where the
      electrochemical generation of the Fenton reagent takes place. While the hydroxyl
      radicals electrochemically produced in-situ, react with the pollutant species
      adsorbed on the activated carbon cathode, the resin compartments administrate and
      collect the iron cation and the hydrated proton species in alternating flow
      direction cycles. The resulting process is a system that does not require acid or
      iron chemical addition to the process while at the same time, renders
      decontaminated water free of iron-dissolved species at neutral pH. The proposed
      electrochemical reactor arrangement is therefore the basis for the design of
      commercially viable electro-Fenton reactors in which the addition and subsequent
      removal of acid and iron chemicals is avoided; two of the currently most limiting
      features for the development of electro-Fenton technology for treating
      wastewater.

PMID- 29448192
TI  - Impact of enzymatic hydrolysis on the quantification of total urinary
      concentrations of chemical biomarkers.
AB  - Human exposure to consumer and personal care products chemicals such as phenols,
      including parabens and other antimicrobial agents, can be assessed through
      biomonitoring by quantifying urinary concentrations of the parent chemical or its
      metabolites, often after hydrolysis of phase II conjugates. Developing suitable
      analytical methods for the concurrent quantification of multiple exposure
      biomarkers is challenging because optimal conditions for the hydrolysis of such
      conjugates (e.g., O-glucuronides, N-glucuronides, sulfates) may differ depending
      on the biomarker. We evaluated the effectiveness of seven commercial hydrolytic
      enzymes to simultaneously hydrolyze N-glucuronides (using the antibacterial
      triclocarban as example compound) and other conjugates (using select phenols and
      parabens as examples) by using on-line solid phase extraction-high performance
      liquid chromatography-isotope dilution-tandem mass spectrometry. Incubation (30
      min, 55  degrees C) with a genetically engineered beta-glucuronidase (IMCS, >=15
      units/MUL urine) hydrolyzed N-glucuronide triclocarban, but did not fully
      hydrolyze the conjugates of phenols and parabens. By contrast, incubation (4 h,
      37  degrees C) with solid beta-glucuronidase (Helix pomatia, Type H-1, >=30
      units/MUL urine) or liquid beta-glucuronidase/arylsulfatase (Helix pomatia, 30
      units/MUL urine [i.e., 30 MUL/100 MUL urine]) in the presence of 100 MUL methanol
      for 100 MUL urine completely hydrolyzed N-glucuronide triclocarban and the
      conjugates of several phenols and parabens, without cleaving the ester bond of
      the parabens to form p-hydroxybenzoic acid. These results highlight the relevance
      of method validation procedures that include optimizing the hydrolysis of phase
      II urinary conjugates (e.g., enzyme type and amount used, reaction time,
      temperature) to quantify accurately and concurrently multiple exposure biomarkers
      for biomonitoring purposes.

PMID- 29448193
TI  - Influence of chloride on the 185 nm advanced oxidation process.
AB  - The use of 185 nm radiation from a conventional low pressure mercury lamp
      generates the hydroxyl radical (OH) from the photolysis of water and offers an
      advanced oxidation process (AOP) for water treatment that does not require
      chemical addition. However, the influence of the water matrix on the process
      differs substantially from that of other ultraviolet and ozone based processes.
      In particular chloride (Cl-), and not water, absorbs the majority of 185 nm
      photons when [Cl-]>20mgL-1 and generates the chlorine atom radical (Cl) as a
      reactive species. Evidence suggests that when Cl- is present, Cl and OH both
      contribute to contaminant degradation to varying extents. Using nonselective
      (carbamazepine) and selective (nitrobenzene) radical probes, as well as
      nonselective (t-butanol), and selective (acetone and acetate) radical scavengers,
      the influence of Cl-, and therefore 185 nm AOP treatment efficiency, is observed
      to strongly depend on four independent second-order radical rate constants.
      Furthermore, ionic strength effects support the assumption that Cl is in
      equilibrium with the relatively nonreactive dichlorine radical anion ().

PMID- 29448194
TI  - Map of impact by acid mine drainage in the river network of The Iberian Pyrite
      Belt (Sw Spain).
AB  - The Iberian Pyrite Belt (IPB), in the southwest of Europe, is characterized by
      high levels of contamination by acid mine drainage (AMD) in a large extent of its
      river network. In this scenario, it is necessary to characterize the degree of
      pollution of the mining leachates in the AMD-generating sources as well as of the
      main receiving watercourses. A map of impact of each basin was developed, based
      on the model proposed by Grande (2011) and the European Directive 98/83/EC that
      defines the quality standards for drinking water. The results indicate that
      practically all the mining leachates exceeded the maximum concentrations
      established by Directive 98/83/CE for Fe and Cd, almost 90% exceeded the limit
      for Mn and 82% for Al. Likewise, Fe, Cd, and Mn caused 'extremely high'
      degradation in most sampled leachates. Similarly, these metals, in addition to
      Pb, produced more pollution in watercourses located downstream of exploitations.

PMID- 29448195
TI  - Factors affecting the 7Be surface concentration and its extremely high
      occurrences over the Scandinavian Peninsula during autumn and winter.
AB  - Relationships between the beryllium-7 activity concentrations in surface air and
      meteorological parameters (temperature, atmospheric pressure, and precipitation),
      teleconnection indices (Arctic Oscillation, North Atlantic Oscillation, and
      Scandinavian pattern) and number of sunspots are investigated using two
      multivariate statistical techniques: hierarchical cluster and factor analysis.
      The beryllium-7 surface measurements over 1995-2011, at four sampling sites
      located in the Scandinavian Peninsula, are obtained from the Radioactivity
      Environmental Monitoring Database. In all sites, the statistical analyses show
      that the beryllium-7 concentrations are strongly linked to temperature. Although
      the beryllium-7 surface concentration exhibits the well-characterised
      spring/summer maximum, our study shows that extremely high beryllium-7
      concentrations, defined as the values exceeding the 90th percentile in the data
      records for each site, also occur over the October-March period. Two types of
      autumn/winter extremes are distinguished: type-1 when the number of extremes in a
      given month is less than three, and type-2 when at least three extremes occur in
      a month. Factor analysis performed for these autumn/winter events shows a weaker
      effect of temperature and a stronger impact of the transport and production
      signal on the beryllium-7 concentrations. Further, the majority of the type-2
      extremes are associated with a very high monthly Scandinavian teleconnection
      index. The type-2 extremes that occurred in January, February and March are also
      linked to sudden stratospheric warmings of the Arctic vortex. Our results
      indicate that the Scandinavian teleconnection index might be a good indicator of
      the meteorological conditions facilitating extremely high beryllium-7 surface
      concentrations over Scandinavia during autumn and winter.

PMID- 29448196
TI  - Bisphenol S induces obesogenic effects through deregulating lipid metabolism in
      zebrafish (Danio rerio) larvae.
AB  - It has been suggested that dramatic increase in obesity may be caused by growing
      exposure to environmental chemicals. In vitro data has suggested bisphenol S
      (BPS), a compound widely used in polycarbonate plastic production, can induce
      lipid accumulation in preadipocytes. However, the mechanisms responsible for BPS
      induced obesity in vivo remain unclear. In this study, we used translucent
      zebrafish (Danio rerio) larvae as a model to investigate the effect of
      environmentally relevant BPS exposure (1, 10, and 100 MUg/L from 2 h to 15 d post
      fertilization) on lipid accumulation, triacylglycerol (TAG) and lipoproteins
      content, and mRNA expression of genes involved in the regulation of lipid
      synthesis, transport, degradation, and storage. We also analyzed activities of
      two enzymes critical to TAG metabolism: lipoprotein lipase and diglyceride
      acyltransferase. Overfed, obese larvae were used as positive control. The results
      indicated that BPS-treated and overfed larvae had much higher TAG levels and
      visceral fat accumulation compared with control. BPS exhibited obesogenic effects
      by interfering with lipid metabolism as evidenced by (a) upregulation of the mRNA
      expression of fasn, acc1, and agpat4 genes encoding enzymes involved in the de
      novo synthesis of TAG in the liver, (b) downregulation of apolipoprotein
      expression, which should reduce TAG transport from the liver, and (c) increase in
      rxralpha expression, which should promote visceral fat accumulation. Our study is
      the first to demonstrate that the obesogenic effects of BPS in zebrafish are
      related to the disruption of TAG metabolism.

PMID- 29448197
TI  - PI3K/AKT signaling pathway involvement in fluoride-induced apoptosis in C2C12
      cells.
AB  - To investigate the mechanisms of fluoride-induced apoptosis, a fluoride-induced
      C2C12 skeletal muscle cell (C2C12 cell) model was established in this study, and
      the viability of the C2C12 cells was measured using an MTT assay. Cell
      morphological changes were observed via haematoxylin and eosin staining and
      transmission electron microscopy. Apoptosis was monitored through Hoechst
      staining. The mRNA and protein expression of PI3K, PDK1, AKT1, BAD, Bcl-2, Bax
      and caspase-9 were detected through real-time PCR and western blotting,
      respectively. The results showed that the survival rates of C2C12 cells decreased
      gradually with an increasing fluoride doses. The C2C12 cell structure was
      seriously damaged by fluoride, presenting with pyknosis, mitochondrial ridge
      disruption and swollen endoplasmic reticulum. Furthermore, the expression of mRNA
      in PI3K, BAD, Bcl-2, Bax and caspase-9 were significantly increased in the
      fluoride group (P < 0.01), while the expression of PDK1 was markedly decreased (P
      < 0.01). The expression of protein in BAD, Bcl-2 and Bax were significantly
      increased in the fluoride group (P < 0.01), while the expression of PDK1 and P
      AKT1 was markedly decreased (P < 0.01). In conclusion, fluoride-induced apoptosis
      in C2C12 cells is related to the PI3K/AKT signaling pathway.

PMID- 29448198
TI  - Assessment of soil metal concentrations in residential and community vegetable
      gardens in Melbourne, Australia.
AB  - Gardening and urban food production is an increasingly popular activity, which
      can improve physical and mental health and provide low cost nutritious food.
      However, the legacy of contamination from industrial and diffuse sources may have
      rendered surface soils in some urban gardens to have metals value in excess of
      recommended guidelines for agricultural production. The objective of this study
      was to establish the presence and spatial extent of soil metal contamination in
      Melbourne's residential and inner city community gardens. A secondary objective
      was to assess whether soil lead (Pb) concentrations in residential vegetable
      gardens were associated with the age of the home or the presence or absence of
      paint. The results indicate that most samples in residential and community
      gardens were generally below the Australian residential guidelines for all tested
      metals except Pb. Mean soil Pb concentrations exceeded the Australian HIL-A
      residential guideline of 300 mg/kg in 8% of 13 community garden beds and 21% of
      the 136 residential vegetable gardens assessed. Mean and median soil Pb
      concentrations for residential vegetable gardens was 204 mg/kg and 104 mg/kg
      (range <4-3341 mg/kg), respectively. Mean and median soil Pb concentration for
      community vegetable garden beds was 102 mg/kg and 38 mg/kg (range = 17-578
      mg/kg), respectively. Soil Pb concentrations were higher in homes with painted
      exteriors (p = 0.004); generally increased with age of the home (p = 0.000); and
      were higher beneath the household dripline than in vegetable garden beds (p =
      0.040). In certain circumstances, the data indicates that elevated soil Pb
      concentrations could present a potential health hazard in a portion of inner-city
      residential vegetable gardens in Melbourne.

PMID- 29448199
TI  - Insights on the criteria of selection of vegetable and mineral dielectric fluids
      used in power transformers on the basis of their biodegradability and toxicity
      assessments.
AB  - Leakage of transformer dielectric fluids is a concern because it may pose a risk
      of environmental contamination. In this study, the deleterious effects of
      vegetable and mineral dielectric fluids in water bodies were investigated using
      biodegradability and acute toxicity tests with Danio rerio and Artemia salina.
      Regarding biodegradability, all four tested vegetable oils (soy, canola,
      sunflower and crambe) were considered as easily biodegradable, presenting
      degradation rates significantly higher than the Lubrax-type mineral fluid. Acute
      toxicity tests were performed in two separate experiments without solution
      renewal. In the first experiment, the organisms were exposed in direct contact to
      different concentrations of vegetable (soy) and mineral (Lubrax) oils. Total soy
      type vegetable oil has a higher toxic effect than Lubrax-type mineral oil. In the
      second experiment, the organisms were exposed to increasing percentages of the
      water-soluble fraction (WSF) of both types of tested oils. The LC50 values for
      the water-soluble fraction of the Lubrax-type mineral oil were about 5 and 8% for
      the Danio rerio and Artemia salina bioindicators, respectively, whereas the
      vegetable oil did not present toxic effect, regardless of its WSF. These results
      have shown that a strict selection of dielectric fluids and monitoring the
      leakage from power transformers is a serious duty of environmental protection
      agencies.

PMID- 29448200
TI  - Influence of ore processing activity on Hg, As and Sb contamination and
      fractionation in soils in a former mining site of Monte Amiata ore district
      (Italy).
AB  - A geochemical study was carried out at the former Abbadia San Salvatore (ASS)
      mining site of the Monte Amiata ore district (Italy). Hg, As and Sb total
      contents and fractionation using a sequential extraction procedure were
      determined in soil and mining waste samples. Ore processing activities provided a
      different contribution to Hg contamination and concentration in soil fractions,
      influencing its behaviour as volatility and availability. Soils of roasting zone
      showed the highest Hg contamination levels mainly due to the deposition of Hg
      released as Hg0 by furnaces during cinnabar roasting. High Hg contents were also
      measured in waste from the lower part of mining dump due to the presence of
      cinnabar. The fractionation pattern suggested that Hg was largely as volatile
      species in both uncontaminated and contaminated soils and mining waste, and
      concentrations of these Hg species increased as contamination increased. These
      findings were in agreement with the fact that the ASS mining site is
      characterized by high Hg concentrations in the air and the presence of Hg0 liquid
      droplets in soil. Volatile Hg species were also prevalent in uncontaminated soils
      likely because the Monte Amiata region is an area characterized by anomalous
      fluxes of gaseous Hg from natural and anthropogenic inputs. At the ASS mining
      site soils were also contaminated by Sb, while As contents were comparable with
      its local background in soil. In all soil and waste samples Sb and As were
      preferentially in residual fraction.

PMID- 29448201
TI  - Trace element dynamics of biosolids-derived microbeads.
AB  - This study focused on quantifying and characterising microbeads in biosolids
      (i.e., treated sewage sludge), and in examining interactions of microbeads with
      trace elements when biosolids are added to soil. Under laboratory conditions,
      batch experiments were conducted to investigate the adsorption of Cu onto pure
      and surface modified microbeads suspended in soil. The ecotoxicity of microbead
      metal complexes to soil microbial activities was also investigated by monitoring
      basal respiration and dehydrogenase activity. Concentrations of the microbeads
      were 352, 146, 324, and 174 particles kg-1 biosolids for <=50, 50-100, 100-250,
      250-1000 MUm size fractions, respectively. The Scanning Electron Microscope (SEM)
      images illustrated wrinkled and fractured surfaces due to degradation. The
      adsorption of dissolved organic matter onto microbeads was confirmed through FT
      IR microscopy, while using Inductively Coupled Plasma Mass Spectrometer (ICP-MS)
      the presence of trace metals including Cd (2.34 ng g-1), Cu (180.64 ng g-1), Ni
      (12.69 ng g-1), Pb (1.17 ng g-1), Sb (14.43 ng g-1), and Zn (178.03 ng g-1) was
      revealed. Surface modified microbeads were capable of adsorbing Cu compared to
      the pure microbeads, which may be attributed to the complexation of Cu with
      dissolved organic matter associated with the microbeads in the matrix. It was
      further revealed that the biosolids derived microbead-metal complexes decreased
      soil respiration (up to ~ 26%) and dehydrogenase activity (up to ~ 39%). Hence,
      microbeads reaching biosolids during wastewater treatment are likely to serve as
      a vector for trace element contamination, transportation, and toxicity when
      biosolids are applied to soil.

PMID- 29448202
TI  - The Correlation Between Serum Chemokines and Clinical Outcome in Patients with
      Advanced Biliary Tract Cancer.
AB  - BACKGROUND: Biliary tract cancers (BTCs) are known to have a dismal prognosis. A
      number of chemokines play important roles in the progress of BTCs. However, the
      serum levels of chemokines in BTCs have not yet been explored. METHODS: The sera
      of healthy donors (n = 8) and patients with BTCs who were enrolled in second line
      sunitinib trials (n = 27) were collected. The concentrations of three kinds of
      chemokines (CXCL5, CXCL8 and CXCL12) were measured using ELISA assay. The median
      concentrations of chemokines were compared between healthy donors and BTC
      patients and the role of chemokines as a prognostic biomarker was examined.
      RESULTS: BTC patients generally had higher serum levels of CXCL5 and CXCL12
      compared to healthy donors. Patients with cholangiocarcinoma showed significantly
      higher levels of serum CXCL12 than patients with gallbladder cancer. In survival
      analysis, only CXCL12 level showed a prognostic impact on overall survival
      (median OS: 6.9 vs. 0.9 months in low CXCL12 vs. high CXCL12, respectively; P =
      .008). High CXCL5 levels were also correlated with poor survival without
      statistical insignificance (median OS: 6.2 vs. 2.0 months in low CXCL5 vs. high
      CXCL5, respectively; P = .070). CONCLUSIONS: There was a significant difference
      in OS according to the level of CXCL12, suggesting that serum CXCL12 levels may
      be a useful surrogate marker for clinical outcome in advanced BTCs.

PMID- 29448203
TI  - Preoperative Anti-Class III beta-Tubulin Antibodies As Relevant Clinical
      Biomarkers in Ovarian Cancer.
AB  - Class III beta-tubulin (TUBB3) overexpression in ovarian cancer (OC) associates
      with poor prognosis. We investigated whether TUBB3 overexpression elicited anti
      TUBB3 antibody production in OC patients and whether these antibodies may have
      diagnostic and prognostic impact. The presence of serum anti-TUBB3 antibodies was
      investigated in 49 untreated OC patients and 44 healthy individuals by an in
      house developed ELISA that used recombinant TUBB3 as the antigen. Receiver
      operating characteristic (ROC) curves were generated to assess the diagnostic
      accuracy of the assay. Anti-TUBB3 antibodies discriminated OC patients and
      healthy individuals with excellent sensitivity and specificity (91.8% and 90.9%,
      respectively). In multivariate analysis, anti-TUBB3 antibody level emerged as an
      independent prognostic factor for progression free and overall survival. The
      ELISA was then optimized using a biotin-labeled TUBB3 C-terminal peptide424-450
      instead of recombinant TUBB3 as the antigen and streptavidin-coated plates. The
      diagnostic role of the anti-TUBB3 antibodies was studied in an independent series
      of 99 OC patients and 80 gynecological benign disease patients. ROC-curve
      analysis showed a valuable diagnostic potential for serum anti-TUBB3 antibodies
      to identify OC patients with higher sensitivity and specificity (95.3% and 97.6%,
      respectively). Overall, our results provide evidence that preoperative anti-TUBB3
      antibody level is a promising diagnostic and prognostic biomarker for the
      management of OC patients.

PMID- 29448204
TI  - Experimental and computational assessment of mycosynthesized CdO nanoparticles
      towards biomedical applications.
AB  - The present study reports the biogenic synthesis of Cadmium Oxide Nanoparticles
      (CdO NPs) using plant pathogenic fungus Nigrospora oryzae culture filtrate.
      Further, the effect of the NPs on the cancer cell line (HeLa) is explored. The
      sample was characterized using Thermogravimetric/Differential Thermal (TG/DTA),
      Powder X-ray Diffraction (XRD), X-ray Photoelectron spectroscopy (XPS), UV
      Visible Diffuse Reflectance Spectroscopy (UV-DRS), Field Emission Transmission
      Electron Microscopy (FE-SEM) with Energy Dispersive X-ray Spectroscopy (EDX),
      High Resolution Transmission Electron Microscopy (HR-TEM) and Selected Area
      Electron Diffraction (SAED) analysis. Antibacterial activity was evaluated
      against both Gram positive and Gram negative bacterial strains and it showed
      maximum activity against Proteus vulgaris. The larvicidal activity was performed
      to evaluate the maximum ability of synthesized CdO NPs against Anopheles
      stephensi. Subsequently, MTT assay also depicted the dose-dependent anticancer
      activity of CdO NPs against cancer cell line (HeLa). Additionally, the inhibitory
      effect of CdO NPs was analyzed through extensive docking with cancerous protein
      agent. Results enlighten that Transketolase protein exhibited high docking score
      of -4.8 k/mol with H-bond interactions found with Lys75 and Asn185 amino acid
      residues. DFT study was performed on CdO to understand the charge transfer
      reaction for the inhibitory mechanism. Convincingly, this study explores the
      understanding of CdO NPs against HeLa cells.

PMID- 29448205
TI  - 6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid attenuates colon
      carcinogenesis via blockade of IL-6 mediated signals.
AB  - In this study, we investigated the in vivo antiproliferative activity of 6,7
      dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (M1) in
      dimethylhydrazine (DMH) induced colorectal carcinoma (CRC) using albino Wistar
      rats. M1 was administered to DMH induced CRC rats at 10 and 25 mg/kg doses for 15
      days. Various physiological, oxidative parameters, histopathology, ELISA, gene
      and protein expression studies were conducted to evaluate the anti-CRC potential
      of M1. The histopathology and biochemical tests indicated the protective action
      of M1 in DMH-induced colon cancer. ELISA confirms that M1 reduced the increased
      concentration of IL-6 more prominently than those of IL-2 and COX-2. Gene
      expression analysis revealed that M1 attenuated the increased mRNA over
      expression of IL-6, JAK2 and STAT3. The result obtained from quantitative western
      blot analysis demonstrated that the CRC condition was produced by the IL-6
      induced activation/phosphorylation of JAK2 and STAT3 and further down-regulated
      with M1 treatment. This evidence was supported well with the application of data
      based mathematical modeling. Applying the fitted model, we predicted the
      quantitative behavior of STAT3 populations not accessible to experimental
      measurement. Later, 1H NMR based serum metabolic profiling was carried out using
      rat sera to investigate the impact of M1 on CRC-induced metabolic alterations. M1
      showed its ability to restore the perturbed metabolites in CRC condition.
      Altogether, our study provided the first time evidence that M1 exhibits anti-CRC
      potential through the blockade of IL-6/JAK2/STAT3 oncogenic signaling.

PMID- 29448206
TI  - Regulation of JAK2/STAT3 and NF-kappaB signal transduction pathways; Veronica
      polita alleviates dextran sulfate sodium-induced murine colitis.
AB  - Ulcerative colitis (UC) is a major inflammatory bowel disease (IBD) has become a
      worldwide emergent disease. Veronica polita (VP) is a medicinal herb that has
      strong antioxidant and anti-inflammatory properties. In the present study, we
      studied the protective effect of VP on dextran sulfate sodium (DSS)-induced
      experimental colitis in mice. Phytochemical screening of VP extract demonstrated
      the presence of high total phenolic and flavonoid contents. Compared with the DSS
      group, VP significantly reduced clinical symptoms with less weight loss, bloody
      stool, shortening of the colon, and the severity of colitis was considerably
      inhibited as evidenced by the reduced disease activity index (DAI) and degree of
      histological damage in the colon and spleen. Also, treatment with VP considerably
      decreased the nitric oxide (NO) and malondialdehyde (MDA) level. VP remarkably
      downregulated the expression of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6), inducible nitric oxide
      synthetase (iNOS) and cyclooxygenase-2 (COX-2) in the colon tissue. Likewise,
      activation of the signal transducer and activator of transcription 3 (STAT3) and
      nuclear factor-kappa B (NF-kappaB) was effectively blocked by VP. Taken together,
      these results demonstrate that VP has an ameliorative effect on colonic
      inflammation mediated by modulation of oxidative stress and inflammatory
      mediators by suppressing the JAK2/STAT3 and NF-kappaB signaling pathways.

PMID- 29448207
TI  - Ferulic acid protects lipopolysaccharide-induced acute kidney injury by
      suppressing inflammatory events and upregulating antioxidant defenses in Balb/c
      mice.
AB  - Sepsis-induced acute kidney injury (AKI) is responsible for 70-80% mortality in
      intensive care patients due to elevated levels of endotoxin, Lipopolysaccharide
      (LPS) caused by gram-negative infections. Ferulic acid (FA), a phenolic
      phytochemical is known for its renal protection on various induced models of
      nephrotoxicity. However, the curative effect of FA in LPS-induced AKI is not well
      studied. This study aimed to investigate the effect of FA on LPS-induced AKI in
      mice model and to understand the protective mechanisms involved, to provide
      evidence for FA in the treatment of AKI. Balb/c mice were treated with FA at 50
      mg/kg and 100 mg/kg dosages after LPS stimulation (10 mg/kg). At the end of the
      intervention, we determined the concentrations of serum creatinine and blood urea
      nitrogen, inflammatory cytokines and histopathological changes in animals. Also,
      the relative protein expression level of TLR4 mediated NF-kappaB signaling
      pathway were studied in kidney tissues. FA treated animals showed upregulation of
      antioxidant defenses and suppression of inflammatory events by inhibiting TLR-4
      mediated NFkappaB activation. However, LPS alone administered group, resulted in
      rapid renal damage with increased levels of blood urea nitrogen and modest
      increase in creatinine; decreased antioxidant defenses and release of
      inflammatory cytokines. The histopathological analysis also revealed the
      protective action of the FA against sepsis induced fibrosis and renal damage. Our
      findings demonstrated that FA exhibits marked protective effects on LPS-induced
      AKI in mice suggesting its chemopotential role for treating AKI in humans.

PMID- 29448208
TI  - Microwave hydrothermal-assisted preparation of novel spinel-NiFe2O4/natural
      mineral composites as microwave catalysts for degradation of aquatic organic
      pollutants.
AB  - In this study, novel spinel-NiFe2O4/natural mineral (sepiolite, diatomite and
      kaolinite) composites were developed using microwave (MW) hydrothermal method,
      and applied in MW-induced catalytic degradation (NiFe2O4/natural mineral/MW) of
      organic pollutants such as sodium dodecyl benzene sulfonate (SDBS), azo fuchsine
      (AF), methyl parathion (MP), and crystal violet (CVL) in solution. Catalytic
      activities of three NiFe2O4/natural mineral composites were compared. The effects
      of material synthesis process parameters such as molar ratios of NiFe2O4 and
      natural mineral, and pH of precursor solutions for synthesizing catalysts, and
      degradation parameters such as MW irradiation time and catalyst reuse cycles were
      also investigated. The principle on NiFe2O4/natural mineral/MW degradation was
      provided. The results reveal that organic pollutants in wastewater can be removed
      completely using NiFe2O4/natural mineral/MW within minutes. NiFe2O4/sepiolite
      shows higher catalytic activity than the others. The calculated degradation rate
      constants are 1.865, 0.672, 0.472, and 0.329 min-1 for SDBS, AF, MP, and CVL,
      respectively, using NiFe2O4/sepiolite/MW system. The performance of
      NiFe2O4/natural mineral can be maintained for three reuse cycles. Active species
      OH, O2-, and h+ play main roles in NiFe2O4/sepiolite/MW degradation. Hence,
      NiFe2O4/sepiolite/MW technology with rapid and cost-effective degradation,
      magnetic separation, and no secondary pollution, demonstrates to be promising in
      treating organic contaminants in wastewater.

PMID- 29448209
TI  - Metagenomic analysis revealed the prevalence of antibiotic resistance genes in
      the gut and living environment of freshwater shrimp.
AB  - Antibiotic resistance disseminating from animals and their environments is a
      public issue that poses significant threats to human health. In the present
      study, the diversity and abundance of antibiotic resistance genes (ARGs) in 15
      samples from the guts and related aquaculture environments (water and sediment)
      of shrimp were investigated. In total, 60 ARGs, 102 ARGs and 67 ARGs primarily
      belonging to 13, 15 and 15 different types were detected in the shrimp gut, pond
      water and sediment samples, respectively. Efflux pump and target modification
      were the predominant resistance mechanisms in all samples. It was found that
      Aeromonas, Yersinia and Clostridium XlVb were significantly correlated with the
      distribution of the ARGs. Besides, the relative abundance of ARGs was positively
      correlated with the levels of mobile genetic elements (MGEs). Moreover, variation
      partitioning analysis showed that MGEs, contributing to 74.46% of the resistome
      variation, played an important role in the affecting of the antibiotic resistome
      than the bacterial communities and their joint effects. Collectively, this study
      provides comprehensive information to better understand the ARG dissemination in
      aquaculture environments and to improve the ecological management of aquatic
      ecosystems.

PMID- 29448210
TI  - Iodate and nitrate transformation by Agrobacterium/Rhizobium related strain DVZ35
      isolated from contaminated Hanford groundwater.
AB  - Nitrate and radioiodine (129I) contamination is widespread in groundwater
      underneath the Central Plateau of the Hanford Site. 129I, a byproduct of nuclear
      fission, is of concern due to a 15.7 million year half-life, and toxicity. The
      Hanford 200 West Area contains plumes covering 4.3 km2 with average 129I
      concentrations of 3.5 pCi/L. Iodate accounts for 70.6% of the iodine present and
      organo-iodine and iodide make up 25.8% and 3.6%, respectively. Nitrate plumes
      encompassing the 129I plumes have a surface area of 16 km2 averaging 130 mg/L. A
      nitrate and iodate reducing bacterium closely related to Agrobacterium, strain
      DVZ35, was isolated from sediment incubated in a 129I plume. Iodate removal
      efficiency was 36.3% in transition cultures, and 47.8% in anaerobic cultures.
      Nitrate (10 mM) was also reduced in the microcosm. When nitrate was spiked into
      the microcosms, iodate removal efficiency was 84.0% and 69.2% in transition and
      anaerobic cultures, respectively. Iodate reduction was lacking when nitrate was
      absent from the growth medium. These data indicate there is simultaneous
      reduction of nitrate and iodate by DVZ35, and iodate is reduced to iodide.
      Results provide the scientific basis for combined nitrogen and iodine cycling
      throughout the Hanford Site.

PMID- 29448211
TI  - An integrated bi-level optimization model for air quality management of Beijing's
      energy system under uncertainty.
AB  - In this study, an interval chance-constrained bi-level programming (ICBP) method
      is developed for air quality management of municipal energy system under
      uncertainty. ICBP can deal with uncertainties presented as interval values and
      probability distributions as well as examine the risk of violating constraints.
      Besides, a leader-follower decision strategy is incorporated into the
      optimization process where two decision makers with different goals and
      preferences are involved. To solve the proposed model, a bi-level interactive
      algorithm based on satisfactory degree is introduced into the decision-making
      processes. Then, an ICBP based energy and environmental systems (ICBP-EES) model
      is formulated for Beijing, in which air quality index (AQI) is used for
      evaluating the integrated air quality of multiple pollutants. Result analysis can
      help different stakeholders adjust their tolerances to achieve the overall
      satisfaction of EES planning for the study city. Results reveal that natural gas
      is the main source for electricity-generation and heating that could lead to a
      potentially increment of imported energy for Beijing in future. Results also
      disclose that PM10 is the major contributor to AQI. These findings can help
      decision makers to identify desired alternatives for EES planning and provide
      useful information for regional air quality management under uncertainty.

PMID- 29448212
TI  - Natural adsorbent based on sawdust for removing impurities in waste lubricants.
AB  - Sawdust was expected to remove impurities in waste lubricant, and was modified
      with sodium hydroxide and triethanolamine, which can ameliorate its surface
      properties and improve its adsorption capacity. The increase of hydroxyl groups,
      the decrease of carbonyl groups and grafting new azyl after modification were
      beneficial for the adsorption of impurities. The surface area of modified sawdust
      is 0.969 m2 g-1, which is nearly 1.39 times as much as raw sawdust. The point of
      zero charge for modified sawdust decreased from 6.75 to 5.68 while the
      crystallinity of modified sawdust increased from 40.35 to 56.16. This research
      discovered that compared with raw sawdust and filter paper, modified sawdust
      possessed superior adsorption performances. The removal percentages for Si, Al,
      Fe, Cu was enhanced from 2.54%, 20.34%, 16.55%, 0.26% to 15.37%, 21.99%, 45.37%,
      4.88%, respectively, while that for oxidation, aromatics, sulphation, soot and
      water was improved by 4.33, 4.69, 0.76, 1.20, 1.28 times at 80  degrees C with
      1000 rpm for 12 h. The research has also explored the optimum adsorption
      conditions (adsorption temperature, adsorption time and rotation rate). The
      modified sawdust showed a stable adsorption capacity for impurities under
      different adsorption conditions.

PMID- 29448213
TI  - Preparation of dumbbell manganese dioxide/gelatin composites and their
      application in the removal of lead and cadmium ions.
AB  - The nano-sized sorbents restrict their practical application in flow-through
      system due to excessive pressure. In this study, dumbbell MnO2/gelatin composites
      were synthesized based on the protein-assisted synthesis technology. Then they
      were immobilized on the amino-modified polymethyl methacrylate (PMMA) plate. SEM,
      TEM, XRD, XPS and FT-IR were employed to study the surface properties and the
      adsorption mechanism of MnO2/gelatin composites. Adsorption experiments for
      Pb(II) and Cd(II) ions were performed to study the adsorption isotherms,
      kinetics, and thermodynamics as well as the influencing factors. The maximum
      adsorption capacities of Pb(II) and Cd(II) ions were 318.7 mg g-1 and 105.1 mg g
      1 respectively. The adsorption process met the pseudo-second-order kinetic model.
      Subsequently, MnO2/gelatin composites modified plates were used to remove the
      heavy metal ions in surface water and wastewater samples. The removal
      efficiencies of Pb(II) ion was changed from 83% (wastewater) to 100% (surface
      water), when the initial concentration was 10 mg L-1. This device exhibited great
      application prospect in the removal of heavy metals taking advantage of its high
      removal efficiency, excellent stability and reusability and ease of operation.

PMID- 29448214
TI  - Nanoscale zero-valent iron-assisted soil washing for the removal of potentially
      toxic elements.
AB  - The present study focuses on soil washing enhancement via soil pretreatment with
      nanoscale zero-valent iron (nZVI) for the remediation of potentially toxic
      elements. To this end, soil polluted with As, Cu, Hg, Pb and Sb was partitioned
      into various grain sizes (500-2000, 125-500 and <125 MUm). The fractions were
      pretreated with nZVI and subsequently subjected, according to grain size, to Wet
      High Intensity Magnetic Separation (WHIMS) or hydrocycloning. The results were
      compared with those obtained in the absence of nanoparticles. An exhaustive
      characterization of the magnetic signal of the nanoparticles was done. This
      provided valuable information regarding potentially toxic elements (PTEs) fate,
      and allowed a metallurgical accounting correction considering the dilution
      effects caused by nanoparticle addition. As a result, remarkable recovery yields
      were obtained for Cu, Pb and Sb, which concentrated with the nZVI in the
      magnetically separated fraction (WHIMS tests) and underflow (hydrocyclone tests).
      In contrast, Hg, concentrated in the non-magnetic fraction and overflow
      respectively, while the behavior of As was unaltered by the nZVI pretreatment.
      All things considered, the addition of nZVI enhanced the efficiency of soil
      washing, particularly for larger fractions (125-2000 MUm). The proposed
      methodology lays the foundations for nanoparticle utilization in soil washing
      operations.

PMID- 29448215
TI  - Synthesis of dual temperature - and pH-responsive yolk-shell nanoparticles by
      conventional etching and new deswelling approaches: DOX release behavior.
AB  - Dual stimuli-responsive yolk-shell nanoparticles with cross-linked poly(acrylic
      acid) (PAA) pH-responsive core and cross-linked poly(2-hydroxyethyl methacrylate)
      (PHEMA) temperature-responsive shell were synthesized via two different methods
      In the first method, silica encapsulated PAA (PAA@SiO2) was used as seed in
      distillation precipitation polymerization (DPP) of HEMA to yield PAA@SiO2@PHEMA
      from which silica layer was etched by HF solution to produce yolk-shell
      PAA@air@PHEMA nanoparticles. In the second method, swollen PAA nanoparticles at
      pH = 10 were used as seeds in emulsion polymerization of HEMA to yield core-shell
      PAA@PHEMA nanoparticles. After dispersion of PAA@PHEMA nanoparticles in acidic
      medium at pH = 2, yolk-shell nanoparticles were formed through deswelling of pH
      responsive cores due to protonation of carboxyl groups. Synthesized nanoparticles
      were characterized using FT-IR, FE-SEM and TEM methods to observe yolk-shell
      nanostructure for both synthesis routes. Stimuli-responsive behavior of the
      nanoparticles was investigated by UV-vis spectrometer where similar behaviors
      were obtained for template-assisted and template-free synthesized yolk-shell
      nanoparticles. Finally, both yolk-shell nanoparticles were examined as potential
      carriers for controlled release of doxorubicin hydrochloride (DOX) anti-cancer
      drug.

PMID- 29448216
TI  - Development of an indolicidin-derived peptide by reducing membrane perturbation
      to decrease cytotoxicity and maintain gene delivery ability.
AB  - Indolicidin (IL) is a cationic antimicrobial peptide and our previous study has
      demonstrated its potential as a cell penetrating peptide (CPP) to promote gene
      delivery. However, the cytotoxicity of IL arisen from its membrane perturbation
      capacity may restrict its clinical application. To promote gene delivery safety
      and efficiency, an almost mirror-symmetric IL derivative, SAP10 (RRWKFFPWRR
      CONH2), was designed in this study. All-atom molecular dynamics (MD) simulations
      were performed to understand the association between SAP10 and model lipid
      bilayers. By comparison with IL, SAP10 with high positively charged density
      resisted its deep insertion into lipid bilayers, which thus reduced its
      perturbation to lipid bilayers and improved biocompatibility. Consequently, we
      further mixed SAP10, polyethylenimine (PEI) and DNA to form the ternary
      nanocomplexes for gene delivery investigation. Both IL and SAP10 weakened the
      interaction between to DNA and PEI, which may be beneficial to promote the
      dissociation of internalized DNA from the carrier molecules. In vitro experiments
      demonstrated that the SAP10-associated ternary nanocomplexes highly promoted the
      transfection efficiency to various cells with low cytotoxicity. The effect of the
      SAP10 on promoting gene delivery was mainly contributed by the adsorbed peptides
      on the nanoparticles rather than the free ones. In particular, the dose of SAP10
      could be increased to broaden the administration window, which ensured its safety
      on transfection. Therefore, our results suggested the argument that the designed
      SAP10 is a safe and an efficient peptide to promote PEI-mediated gene delivery.

PMID- 29448217
TI  - A simple approach for fabrication of optical affinity-based bioanalytical
      microsystem on polymeric PEN foils.
AB  - Herein, we report a novel concept of low-cost flexible platform for fluorescence
      based biosensor. The surface of polyethylene naphthalate (PEN) foil was exposed
      to KrF excimer laser through a photolitographic contact mask. Laser initiated
      surface modification resulted in micro-patterned areas with surface functional
      groups available for localized covalent immobilization of biotin. High affinity
      binding protein (albumin-binding domain (ABD) of protein G, Streptococcus G148)
      recognizing human serum albumin (HSA), genetically fused with streptavidin (SA
      ABDwt), was immobilized on the micro-patterned surface through biotin
      streptavidin coupling. Fluorescently labelled HSA analyte was detected in several
      blocking environments, in 1% bovine serum albumin (BSA) and 6% fetal serum
      albumin (FBS), respectively. We conclude that the presented novel concept enabled
      us to micropattern functional biosensing layers on the surface of PEN foil in a
      fast and easy way. It brings all necessary aspects for continuous roll-to-roll
      fabrication of low-cost optical bioanalytical devices.

PMID- 29448218
TI  - Polymer adhesion predictions for oral dosage forms to enhance drug administration
      safety. Part 1: In vitro approach using particle interaction methods.
AB  - Solid oral dosage forms (SODF) are drug vehicles commonly prescribed by
      physicists in primary and secondary cares, as they are the most convenient for
      the patient and facilitate therapy management. Concerns regarding unintended
      adhesion of SODF during oro-esophageal transit remain, especially in multimorbid
      patients, bedridden patients and patients suffering from dysphagia. Hence, this
      factor should be considered during the development of SODF, and more attention
      should be given on the design of appropriate surface conditions considering
      patients with swallowing problems. The aim of this work was to estimate the low
      mucoadhesion strength of different pharmaceutical polymers frequently used in
      coating technologies, since this property is thought to have impact on the
      mucoadhesive profile of SODF during oro-esophageal transit. In an approach using
      in vitro methods based on particle interactions, polyethylene glycol grades (PEG)
      showed the lowest interaction forces suggesting a more favorable in vivo
      performance than hydroxypropyl methylcellulose (HPMC), which was found to have
      the highest particle interaction. Preference should be given to coating
      formulations with lower concentrations of polymer and grades with low molecular
      weight. In addition, rheological measurements should be adopted when targeting
      poor mucoadhesive polymers.

PMID- 29448219
TI  - Gait & Posture Special Issue: Gait adaptations in response to obstacle type in
      fallers with Parkinson's disease.
AB  - BACKGROUND: Gait impairment places older adults and people with Parkinson's
      disease (PD) at an increased risk of falls when walking over obstacles.
      Increasing the height of obstacles results in greater challenge to balance
      however little is known about the demands encountered when negotiating obstacles
      of greater depth which may be greater for PD who often walk with a short,
      shuffling gait. RESEARCH QUESTION: To describe gait adaptation in older adults
      and people with PD when walking over long and tall obstacles. METHODS: 20 people
      with PD and 13 older adults with a history of falls walked across an instrumented
      walkway under four conditions: level walking, and over a small, long and tall
      obstacle. Differences due to group, step and obstacle type were evaluated using
      General Linear Models. RESULTS: An increased step duration, longer single limb
      support and a wider step (p < .033) were observed when crossing the tall obstacle
      for both older adults and PD. The PD group completed the crossing steps more
      slowly than controls, with a shorter step and longer single limb support (p <
      .043). Obstacle type did not significantly influence step length. SIGNIFICANCE:
      The greatest temporal-spatial adaptations were elicited when participants
      negotiated the tall obstacle. Electing a wider step when crossing the tall
      obstacle was a strategy common to both faller groups (older adults and PD). The
      tall obstacle presented added challenge for PD who spent longer in single limb
      support during the crossing steps compared to controls. The long obstacle did not
      cause a disproportionate change in step length in people with PD, and we suggest
      that the obstacle may have acted as a visual cue in this group.

PMID- 29448220
TI  - Trunk postural balance and low back pain: Reliability and relationship with
      clinical changes following a lumbar stabilization exercise program.
AB  - Lumbar stabilization programs reduce pain and disability, but the mechanisms of
      action underlying this treatment are unknown. Trunk postural control during
      unstable sitting represents a surrogate measure of motor control mechanisms
      involved to maintain the dynamic stability of the spine. This exploratory study
      aimed to determine the reliability of trunk postural control measures over an 8
      week interval, their sensitivity to low back pain status and treatment and their
      relationship with clinical outcomes. Trunk postural control measures were
      determined in patients with low back pain before and after an 8-week lumbar
      stabilization exercise program. Healthy controls were assessed over the same
      interval, but without any treatment, to determine the reliability of the measures
      and act as a control group at baseline. The kinematics of a wobble chair during
      unstable sitting was summarized using different linear and nonlinear measures
      quantifying the quantity and quality of movement, respectively. The reliability
      of the measures was moderate to excellent. The results showed significant
      reduction in pain and disability following the intervention. While no impairment
      at baseline scores was found, some linear and nonlinear measures changed over the
      intervention period among the patient group. However, for nonlinear measures
      only, significant correlations were detected with the change scores of pain and
      disability. The change of measures over the intervention period was likely due to
      learning rather than the intervention as similar alteration was detected in the
      healthy subjects. The results suggest that only the quality (not the quantity) of
      movement may have relationship with pain and disability.

PMID- 29448221
TI  - Trip-specific training enhances recovery after large postural disturbances for
      which there is NO expectation.
AB  - PURPOSE: Informed consent usually provides foreknowledge of experimental methods
      that can potentially increase expectation of stimuli and, therefore, influence
      the response. We determined the effects of increased expectation and trip
      specific training on the recovery response following a treadmill-delivered, trip
      specific disturbance. To deliver unexpected disturbances, subjects were deceived
      during the informed consent process. The primary hypothesis was that the recovery
      response following an expected postural disturbance would be characterized by
      trunk kinematics that have been shown to decrease the likelihood of a fall,
      compared to following an unexpected postural disturbance. We further hypothesized
      that following an unexpected postural disturbance, the recovery response of the
      subjects who had completed a trip-specific training protocol would be more
      biomechanically favorable to recovery compared to those of subjects who had not
      received the training. METHODS: Young adults were randomized into Untrained or
      Trained groups. During the informed consent process, the purpose of the study was
      explained to subjects in both groups as being to determine the effect of trip
      specific training on postural sway while performing an attention-demanding task.
      Untrained subjects completed two trials during which they minimized their
      postural sway. During the second trial, an unexpected disturbance was delivered
      while they performed the attention-demanding task. Trained subjects performed a
      pre-training postural sway trial, followed by the delivery of a series of
      expected, training disturbances. Finally, an unexpected disturbance was delivered
      while they minimized postural sway and performed the attention-demanding task.
      RESULTS: Expectation significantly improved trunk kinematics (p < .05). In
      addition, participation in the trip-specific training protocol following the
      unexpected disturbance the trunk kinematics of the Trained subjects were more
      biomechanically favorable to recovery than those of the Untrained subjects (p <
      .01). CONCLUSION: Improved trunk kinematics following trip-specific training may
      be independent of the extent to which the disturbance is expected.

PMID- 29448222
TI  - A colorimetric broth microdilution method for assessment of Helicobacter pylori
      sensitivity to antimicrobial agents.
AB  - Helicobacter pylori is a major infective etiological agent of the upper
      gastrointestinal tract diseases. The bacterium exhibits resistance to various
      conventional antibiotics, being usually challenging for eradication. Since there
      is an urge to consider alternative therapeutic strategies, the aim of the study
      was to examine selected essential oils of plants belonging to families
      Cupressaceae (Juniperus communis) and Lamiaceae (Hyssopus officinalis, Salvia
      officinalis, Melissa officinalis, Lavandula angustifolia, Ocimum basilicum and
      Thymus serpyllum) against H. pylori, using an improved microdilution broth
      method. The oils were examined in concentration range from 0.03 to 4 MUL/mL. The
      method comprises Brain-heart infusion broth supplemented with yeast extract,
      horse serum and IsoVitaleX. After 3 day incubation, an equal volume of double
      strengthen Christensen's urea was added into each well and incubated for
      additional 4 h. In wells with present H. pylori, the medium changed color from
      yellow to purple, allowing MIC determination even without a microtitre plate
      reader. The microtitre format method is convenient as it is less expensive,
      easier to perform and requires less amount of an anti-H. pylori agent. The
      improved method enhances specificity to H. pylori, as fast urease activity is
      almost an exclusive property of this bacterium. The application of the second
      step incubation with Christensen's urea decreases the possibility of false
      positive/negative results due to contaminant growth or commonly poor H. pylori
      growth. Among the examined oils, J. communis, H. officinalis and O. basilicum
      were not active with the highest applied concentrations, while the most active
      was T. serpyllum, with MIC 2.0-4.0 MUL/mL. This is the first report on essential
      oils activity of T. serpyllum and H. officinalis against H. pylori.

PMID- 29448223
TI  - 2D transition metal carbide MXene as a robust biosensing platform for enzyme
      immobilization and ultrasensitive detection of phenol.
AB  - MXene-Ti3C2, as a new class of two-dimensional (2D) transition metal carbides (or
      nitrides), has been synthesized by exfoliating pristine Ti3AlC2 phases with
      hydrofluoric acid. The SEM and XRD images show that the resultant MXene possesses
      a graphene-like 2D nanostructure. and the surface of MXene has been partially
      terminated with -OH, thus providing a favorable microenvironment for enzyme
      immobilization and retaining their bioactivity and stability. Considering the
      unique metallic conductivity, biocompatibility and good dispersion in aqueous
      phase, the as-prepared MXene was explored as a new matrix to immobilize
      tyrosinase (a model enzyme) for fabricating a mediator-free biosensor for
      ultrasensitive and rapid detection of phenol. The varying electrochemical
      measurements were used to investigate the electrochemical performance of MXene
      based tyrosinase biosensors. The results revealed that the direct electron
      transfer between tyrosinase and electrode could be easily achieved via a surface
      controlled electrochemical process. The fabricated MXene-based tyrosinase
      biosensors exhibited good analytical performance over a wide linear range from
      0.05 to 15.5 MUmol L-1, with a low detection limit of 12 nmol L-1 and a
      sensitivity of 414.4 mA M-1. The proposed biosensing approach also demonstrated
      good repeatability, reproducibility, long-term stability and high recovery for
      phenol detection in real water samples. With those excellent performances, MXene
      with graphene-like structure is proved to be a robust and versatile
      electrochemical biosensing platform for enzyme-based biosensors and biocatalysis,
      and has wide potential applications in biomedical detection and environmental
      analysis.

PMID- 29448224
TI  - A review on electrochemical detection of serotonin based on surface modified
      electrodes.
AB  - Serotonin is one of the important neurotransmitters of our body. It's abnormal
      concentration is associated with multiple disorders and diseases. Sensitive and
      precise electrochemical determination of serotonin is not possible with bare
      working electrodes due to various reasons viz. electro-chemical fouling, presence
      of other biological molecules having similar oxidation potential, and lower
      concentration of serotonin in biological samples. Surface modification of working
      electrode is required for fast, precise, selective, and sensitive detection of
      serotonin. We have extensively reviewed the research approaches where serotonin
      has been sensitively detected using surface modified electrodes in the presence
      of other interfering agents. This review aims at presenting the electrochemical
      detection of serotonin using various surface modified electrodes such as glassy
      carbon, graphite, carbon fiber, diamond, screen printed, ITO, and metal
      electrodes modified with conducting polymers and polyelectrolytes, carbon
      nanomaterials, metal or metal oxide nanoparticles, biological compounds, and
      other conducting materials. The analytical figures of merits of various research
      approaches for detection of serotonin have been compared in the article. The
      properties of material used for surface modification, chemical interactions at
      the interfaces, and electrocatalytic effects of modified surfaces on sensing of
      serotonin have been thoroughly discussed in this review.

PMID- 29448225
TI  - A dye-sensitized solar cell acting as the electrical reading box of an
      immunosensor: Application to CEA determination.
AB  - Monitoring cancer biomarkers in biological fluids has become a key tool for
      disease diagnosis, which should be of easy access anywhere in the world. The
      possibility of reducing basic requirements in the field of electrochemical
      biosensing may open doors in this direction. This work proposes for this purpose
      an innovative electrochemical immunosensing system using a photovoltaic cell as
      an electrical reading box. Immunosensing ensures accuracy, the electrochemical
      ground of the device ensures sensitivity and detectability, and the photovoltaic
      cell drives the system towards electrical autonomy. As proof-of-concept,
      Carcinoembryonic antigen (CEA) was used herein, a cancer biomarker of clinical
      relevance. In brief, a conductive glass with a fluorine doped tin oxide film was
      used as conductive support and modified with anti-CEA by means of a bottom-up
      approach. All stages involved in the biochemical modification of the FTO surface
      were followed by electrochemical techniques, namely electrochemical impedance
      spectroscopy and cyclic voltammetry. This electrode acted as counter electrode of
      a dye-sensitized solar cells, and the electrical output of this cell was
      monitored for the different concentrations of CEA. Under optimized conditions,
      the device displayed a linear behaviour against CEA concentration, from 5 pg/mL
      to 15 ng/mL. The immunosensor was applied to the analysis of CEA in urine from
      healthy individual and spiked with the antigen. Overall, the presented approach
      demonstrates that photovoltaic cells may be employed as an electrical reading box
      of electrochemical biosensors, yielding a new direction towards autonomous
      electrochemical biosensing.

PMID- 29448226
TI  - Insights into the interface effect in Pt@BiOI/ZnO ternary hybrid composite for
      efficient photodegradation of phenol and photogenerated charge transfer
      properties.
AB  - In this work, the ternary hybrid photocatalyst composed of ZnO nanorods with BiOI
      and Pt NPs (denoted as Pt@BiOI/ZnO) was fabricated by a simple three-step method.
      The as-prepared samples were characterized by scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), UV-Vis diffuse reflectance spectrometry
      (DRS) and X-ray photoelectron spectroscopy (XPS), which proved the strong
      interaction has occurred among the Pt, BiOI and ZnO. The phenol degradation test
      showed that the Pt@BiOI/ZnO ternary hybrid composite exhibited the maximum
      photodegradation efficiency of phenol (99.9%) under UV irradiation within 30 min
      compared to Pt/BiOI, BiOI/ZnO binary composites as well as Pt/ZnO. Additionally,
      the transient photovoltage (TPV), steady-state PL spectra and time-resolved PL
      spectra were used to investigate the possible mechanism for photocatalytic
      performance. Our results elaborated that the enhanced photocatalyticactivity was
      mainly attributed to the synergetic effect of Pt/ZnO and BiOI/ZnO interfaces.
      Conversely, the interfacial interaction of Pt/BiOI is little contribution,
      indicating that the effective interfaces design is very important for the
      degradation of phenol in the preparation process of ternary hybrid photocatalyst.
      These findings will contribute to developing high efficiency photocatalysts for
      application in environmental remediation.

PMID- 29448227
TI  - Alignment of nematic liquid crystals decorated with gemini surfactants and
      interaction of proteins with gemini surfactants at fluid interfaces.
AB  - A series of cationic gemini surfactants with diverse chemical structures, that
      is, imidazolium-based gemini surface active ionic liquids (gemini IM-SAILs) with
      different alkyl chain length or spacer length, viz. 1,s-bis(3-alkylimidazolium-1
      yl) ethane bromide ([Cn-s-Cnim]Br2; s = 2, n = 6, 8, 10, 12, 16; n = 12, s = 2,
      4, 6, 10), and quaternary ammonium-based gemini surfactants (gemini QASaa) with
      different symmetries, viz. 1,2-bisalkylquaternary ammonium bromide (m-2-n; m =
      12, 14, 16, n = 8, 10, 12, m + n = 24), were synthesized and utilized to decorate
      aqueous/liquid crystal interfaces (ALI). Initially, the optical response of the
      LCs changed from bright to dark after incubation with gemini IM-SAILs (except [C6
      2-C6im]Br2) or gemini QASaa aqueous solutions, due to the formation of stable
      surfactant monolayers at the ALI. We verify that gemini IM-SAILs with shorter
      spacer or longer hydrophobic chains are more conducive to adsorption onto the
      interface, and gemini IM-SAILs form monolayers more easily than the corresponding
      monomers or gemini QASaa. Interestingly, a dark-to-bright shift in the optical
      image of the LCs subsequently occurred after the fluid interface decorated with
      the gemini surfactants came into contact with Bovine serum albumin (BSA), a
      negatively charged protein in neutral environments, whereas the optical
      appearance of LCs did not change upon addition of two other proteins with
      positive charge (viz. lysozyme and trypsin). Therefore, based on the different
      action mechanisms, a low-cost, label-free, and convenient LC-based sensing
      platform using the gemini surfactant-decorated LC interface was constructed for
      identification of the proteins with opposite charges.

PMID- 29448228
TI  - Enhanced demulsification from aqueous media by using magnetic chitosan-based
      flocculant.
AB  - A series of quaternized chitosan (QC)-grafted magnetic nanoparticles (MNPs) were
      successfully synthesized for demulsification from aqueous environments. Fe3O4
      MNPs were synthesized by using a coprecipitation method, followed by surface
      coating with silica and aminopropyl to form a surface for further grafting of QC
      molecular chains. The synthetic magnetic flocculants were characterized by
      various technologies and their demulsification performances were evaluated in
      detail as a function of dosage, QC grafting ratio (Gq), pH and magnetic field.
      Results showed that pH did not significantly affect oil-water separation
      performance and MNPs with high Gq exhibited enhanced separation efficiency. The
      separation capacity was estimated to be >105 mg of diesel oil/mg of magnetic
      flocculant. Recycling experiment indicated the magnetic flocculant could be
      recycled up to at least 7 cycles at various pH levels. The grafted QC layer
      endowed the hybrid MNPs with permanent positive surface charges, thus allowing
      them to flocculate negatively charged oil droplets via electrostatic patching.
      The magnetic field could not only accelerate the separation of resulting flocs,
      but also remove the MNPs-coated dispersed oil droplets. In conclusion, QC-grafted
      MNPs provide a potentially new technique for developing environmentally friendly
      and highly efficient magnetic flocculant for practical demulsification
      applications.

PMID- 29448229
TI  - Sulfuric acid etching for fabrication of porous MnO2 for high-performance
      supercapacitor.
AB  - We developed a facile and efficient route to prepare highly porous nanostructure
      MnO2 by etching of proton-type layered manganese oxide (H-MnO2) with sulfuric
      acid (H2SO4). Results from TEM images and N2 adsorption showed that H2SO4 etching
      created porous MnO2 with average pore size of about 4 nm and high specific
      surface area (315 m2 g-1). With such porous structure, the obtained MnO2 exhibits
      a high specific capacitance of 253 F g-1 and enhanced rate capability (62.1%
      capacitance retention from 0.5 to 10 A g-1) when comparing with the H-MnO2
      precursor (154 F g-1, 45.5%) and annealed H-MnO2 in the absence of H2SO4 (134 F g
      1, 43.3%). The excellent capacitive properties demonstrate that creation of
      porous structure on H-MnO2 not only provides large ion-accessible surface area
      for efficient charge storage, but also to some extent promotes the kinetics of
      electrochemical reactions.

PMID- 29448230
TI  - Reversible modulation of the redox activity in conducting polymer nanofilms
      induced by hydrophobic collapse of a surface-grafted polyelectrolyte.
AB  - We present the covalent modification of a Pani-like conducting polymer
      (polyaminobenzylamine, PABA) by grafting of a polyelectrolyte brush (poly [2
      (methacryloyloxy)-ethyl-trimethylammonium chloride], PMETAC). As PABA has extra
      pendant amino moieties, the grafting procedure does not affect the backbone
      nitrogen atoms that are implicated in the electronic structure of the conducting
      polymers. Moreover, perchlorate anions interact very strongly with the quaternary
      ammonium pendant groups of PMETAC through ion pairing. Therefore, the grafting
      does not only keep the electroactivity of PABA in aqueous solutions but it adds
      the ion-actuation properties of the PMETAC brush to the modified electrode as
      demonstrated by contact angle measurements and electrochemical methods. In this
      way, the conjugation of the electron transfer properties of the conducting
      polymer with the anion responsiveness of the integrated brush renders perchlorate
      actuation of the electrochemical response. These results constitute a rational
      integration of nanometer-sized polymer building blocks that yields synergism of
      functionalities and illustrate the potentialities of nanoarchitectonics for
      pushing the limits of soft material science into the nanoworld.

PMID- 29448231
TI  - Capacity building of midwifery faculty to implement a 3-years midwifery diploma
      curriculum in Bangladesh: A process evaluation of a mentorship programme.
AB  - When a midwifery diploma-level programme was introduced in 2010 in Bangladesh,
      only a few nursing faculty staff members had received midwifery diploma-level.
      The consequences were an inconsistency in interpretation and implementation of
      the midwifery curriculum in the midwifery programme. To ensure that midwifery
      faculty staff members were adequately prepared to deliver the national midwifery
      curriculum, a mentorship programme was developed. The aim of this study was to
      examine feasibility and adherence to a mentorship programme among 19 midwifery
      faculty staff members who were lecturing the three years midwifery diploma-level
      programme at ten institutes/colleges in Bangladesh. The mentorship programme was
      evaluated using a process evaluation framework: (implementation, context,
      mechanisms of impact and outcomes). An online and face-to-face blended mentorship
      programme delivered by Swedish midwifery faculty staff members was found to be
      feasible, and it motivated the faculty staff members in Bangladesh both to
      deliver the national midwifery diploma curriculum as well as to carry out
      supportive supervision for midwifery students in clinical placement. First, the
      Swedish midwifery faculty staff members visited Bangladesh and provided a two
      days on-site visit prior to the initiation of the online part of the mentorship
      programme. The second on-site visit was five-days long and took place at the end
      of the programme, that being six to eight months from the first visit. Building
      on the faculty staff members' response to feasibility and adherence to the
      mentorship programme, the findings indicate opportunities for future scale-up to
      all institutes/collages providing midwifery education in Bangladesh. It has been
      proposed that a blended online and face-to-face mentorship programme may be a
      means to improving national midwifery programmes in countries where midwifery has
      only recently been introduced.

PMID- 29448232
TI  - Jump-and-return sandwiches: A new family of binomial-like selective inversion
      sequences with improved performance.
AB  - A new family of binomial-like inversion sequences, named jump-and-return
      sandwiches (JRS), has been developed by inserting a binomial-like sequence into a
      standard jump-and-return sequence, discovered through use of a stochastic Genetic
      Algorithm optimisation. Compared to currently used binomial-like inversion
      sequences (e.g., 3-9-19 and W5), the new sequences afford wider inversion bands
      and narrower non-inversion bands with an equal number of pulses. As an example,
      two jump-and-return sandwich 10-pulse sequences achieved 95% inversion at offsets
      corresponding to 9.4% and 10.3% of the non-inversion band spacing, compared to
      14.7% for the binomial-like W5 inversion sequence, i.e., they afforded non
      inversion bands about two thirds the width of the W5 non-inversion band.

PMID- 29448233
TI  - Earth's field NMR detection of oil under arctic ice-water suppression.
AB  - Earth's field NMR has been developed to detect oil trapped under or in Arctic sea
      ice. A large challenge, addressed here, is the suppression of the water signal
      that dominates the oil signal. Selective suppression of water is based on
      relaxation time T1 because of the negligible chemical shifts in the weak earth's
      magnetic field, making all proton signals overlap spectroscopically. The first
      approach is inversion-null recovery, modified for use with pre-polarization. The
      requirements for efficient inversion over a wide range of B1 and subsequent
      adiabatic reorientation of the magnetization to align with the static field are
      stressed. The second method acquires FIDs at two durations of pre-polarization
      and cancels the water component of the signal after the data are acquired. While
      less elegant, this technique imposes no stringent requirements. Similar water
      suppression is found in simulations for the two methods. Oil detection in the
      presence of water is demonstrated experimentally with both techniques.

PMID- 29448235
TI  - The effects of screen media content on young children's executive functioning.
AB  - Children's exposure to screen-based media has raised concerns for many reasons.
      One reason is that viewing particular television content has been shown to
      negatively affect children's executive functioning. Yet, it is unclear whether
      interacting with a touchscreen device affects executive functioning in the same
      way as the television research suggests. In the current study, 96 2- and 3-year
      old children completed executive functioning measures of working memory and
      response inhibition and task switching before and after a brief screen
      intervention consisting of watching an educational television show, playing an
      educational app, or watching a cartoon. Children's ability to delay gratification
      was also assessed. Results indicate that the type of screen intervention had a
      significant effect on executive functioning performance. Children were more
      likely to delay gratification after playing an educational app than after viewing
      a cartoon. In particular instances, children's working memory improved after
      playing the educational app. These findings emphasize that, for young children's
      executive functioning, interactivity and content may be more important factors to
      consider than simply "screen time."

PMID- 29448234
TI  - Gene expression changes in the ventral hippocampus and medial prefrontal cortex
      of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking.
AB  - Binge drinking of alcohol during adolescence is a serious public health concern
      with long-term consequences, including decreased hippocampal and prefrontal
      cortex volume and deficits in memory. We used RNA sequencing to assess the
      effects of adolescent binge drinking on gene expression in these regions. Male
      adolescent alcohol-preferring (P) rats were exposed to repeated binge drinking
      (three 1-h sessions/day during the dark/cycle, 5 days/week for 3 weeks starting
      at 28 days of age; ethanol intakes of 2.5-3 g/kg/session). Ethanol significantly
      altered the expression of 416 of 11,727 genes expressed in the ventral
      hippocampus. Genes and pathways involved in neurogenesis, long-term potentiation,
      and axonal guidance were decreased, which could relate to the impaired memory
      function found in subjects with adolescent alcohol binge-like exposure. The
      decreased expression of myelin and cholesterol genes and apparent decrease in
      oligodendrocytes in P rats could result in decreased myelination. In the medial
      prefrontal cortex, 638 of 11,579 genes were altered; genes in cellular stress and
      inflammatory pathways were increased, as were genes involved in oxidative
      phosphorylation. Overall, the results of this study suggest that adolescent binge
      like alcohol drinking may alter the development of the ventral hippocampus and
      medial prefrontal cortex and produce long-term consequences on learning and
      memory, and on control of impulsive behaviors.

PMID- 29448236
TI  - Sleep problems and suicidal behaviors in college students.
AB  - Using a large sample of college students, objectives were to examine (1) the
      overlap between poor sleep and suicide risk status, (2) whether poor sleep was
      associated with suicide behaviors above and beyond depression, (3) whether sleep
      problems and depression interacted to predict increased suicidal behaviors or
      risk, and (4) which specific components of sleep were uniquely associated with
      suicidal behaviors. Participants were 1700 college students (ages 18-29 years;
      65% female) from two universities who completed measures assessing sleep,
      depressive symptoms, and suicidal behaviors (Suicidal Behaviors Questionnaire
      Revised [SBQ-R], a composite measure including ideation, past attempt, disclosure
      to others, and future likelihood of suicide that includes a cutoff for
      determining participants with suicide risk). Approximately one-quarter (24%) of
      participants were classified with suicide risk. Four-fifths (82.7%) of
      participants classified with suicide risk also met cutoff criteria for sleep
      problems; conversely, almost one-third (31.3%) of the participants classified
      with sleep problems were also classified with suicide risk. Total sleep problems
      remained significantly associated with suicidal behaviors above and beyond
      depressive symptoms, though sleep and depression did not interact to predict
      suicidal behaviors or risk. When considered together and controlling for sex, the
      odds of being classified with suicide risk were 6.54 times greater for
      participants with elevated depressive symptoms and 2.70 times greater for
      participants with sleep problems. Analyses examining specific sleep domains found
      shorter sleep duration, having bad dreams, feeling too cold while sleeping, and
      sleep medication use to each be independently associated with suicidal behaviors.
      Findings add to a growing body of literature linking sleep and suicide in college
      students.

PMID- 29448237
TI  - The effect of multimorbidity on the gap between global and age-comparative self
      rated health scores among the Korean elderly.
AB  - Most of the behavior change models regard perceived health status as a motivation
      for healthy behaviors or chronic disease self-management. The aim of this study
      was to examine the association between the number of chronic diseases and the
      difference between global and age-comparative self-rated health scores (GSRH and
      ASRH). We used national representative survey data pertaining to the elderly in
      2011 from the Korea Institute for Health and Social Affairs. In total, 10,003
      participants (>=60 years old) were selected from those who had completed the
      survey in 2008. Multinomial logistic regression was used to estimate relative
      risk ratios (RRR) with 95% confidence intervals. Demographic factors,
      socioeconomic status, social connection, and healthy life style were adjusted.
      Individuals with many chronic diseases were more likely to have a positive gap,
      resulting in a better ASRH score relative to GSRH (p for trend <0.001): 1-2
      diseases (RRR = 1.30, 95% CI = 1.07-1.57), 3-4 diseases (RRR = 1.90, 95% CI =
      1.55-2.32), and >=5 diseases (RRR = 1.75, 95% CI = 1.39-2.20). In addition, the
      association between the number of chronic diseases and a positive gap varied by
      sex and living area. Our results suggest that a positive gap between GSRH and
      ASRH that indicates an overestimated age-comparative health, was associated with
      the number of chronic diseases. Female or urban-living people had stronger
      associations. Further research is needed to understand how the gap between GSRH
      and ASRH could be an alternative measure of SRH and a predictor of major health
      outcomes.

PMID- 29448239
TI  - Bioaccessibility and bioavailability of environmental semi-volatile organic
      compounds via inhalation: A review of methods and models.
AB  - Semi-volatile organic compounds (SVOCs) present in indoor environments are known
      to cause adverse health effects through multiple routes of exposure. To assess
      the aggregate exposure, the bioaccessibility and bioavailability of SVOCs need to
      be determined. In this review, we discussed measurements of the bioaccessibility
      and bioavailability of SVOCs after inhalation. Published literature related to
      this issue is available for 2,3,7,8-tetrachlorodibenzo-p-dioxin and a few
      polycyclic aromatic hydrocarbons, such as benzo[a]pyrene and phenanthrene. Then,
      we reviewed common modeling approaches for the characterization of the gas- and
      particle-phase partitioning of SVOCs during inhalation. The models are based on
      mass transfer mechanisms as well as the structure of the respiratory system,
      using common computational techniques, such as computational fluid dynamics.
      However, the existing models are restricted to special conditions and cannot
      predict SVOC bioaccessibility and bioavailability in the whole respiratory
      system. The present review notes two main challenges for the estimation of SVOC
      bioaccessibility and bioavailability via inhalation in humans. First, in vitro
      and in vivo methods need to be developed and validated for a wide range of SVOCs.
      The in vitro methods should be validated with in vivo tests to evaluate human
      exposures to SVOCs in airborne particles. Second, modeling approaches for SVOCs
      need to consider the whole respiratory system. Alterations of the respiratory
      cycle period and human biological variability may be considered in future
      studies.

PMID- 29448238
TI  - Parsing the heterogeneity of depression: An exploratory factor analysis across
      commonly used depression rating scales.
AB  - BACKGROUND: Due to the heterogeneity of depressive symptoms-which can include
      depressed mood, anhedonia, negative cognitive biases, and altered activity levels
      researchers often use a combination of depression rating scales to assess
      symptoms. This study sought to identify unidimensional constructs measured across
      rating scales for depression and to evaluate these constructs across clinical
      trials of a rapid-acting antidepressant (ketamine). METHODS: Exploratory factor
      analysis (EFA) was conducted on baseline ratings from the Beck Depression
      Inventory (BDI), the Hamilton Depression Rating Scale (HAM-D), the Montgomery
      Asberg Depression Rating Scale (MADRS), and the Snaith-Hamilton Pleasure Rating
      Scale (SHAPS). Inpatients with major depressive disorder (n = 76) or bipolar
      depression (n = 43) were participating in clinical ketamine trials. The
      trajectories of the resulting unidimensional scores were evaluated in 41 subjects
      with bipolar depression who participated in clinical ketamine trials. RESULTS:
      The best solution, which exhibited excellent fit to the data, comprised eight
      factors: Depressed Mood, Tension, Negative Cognition, Impaired Sleep, Suicidal
      Thoughts, Reduced Appetite, Anhedonia, and Amotivation. Various response patterns
      were observed across the clinical trial data, both in treatment effect (ketamine
      versus placebo) and in degree of placebo response, suggesting that use of these
      unidimensional constructs may reveal patterns not observed with traditional
      scoring of individual instruments. LIMITATIONS: Limitations include: 1) small
      sample (and related inability to confirm measurement invariance); 2) absence of
      an independent sample for confirmation of factor structure; and 3) the treatment
      resistant nature of the population, which may limit generalizability.
      CONCLUSIONS: The empirical identification of unidimensional constructs creates
      more refined scores that may elucidate the connection between specific symptoms
      and underlying pathophysiology.

PMID- 29448240
TI  - Evaluation of production cross-sections for 186Re theranostic radionuclide via
      charged-particle induced reactions on Tungsten.
AB  - 186Re (T1/2 = 89.24 h, [Formula: see text] 346.7 keV, [Formula: see text] ), an
      intense beta-emitter shows great potential to be used as an active material in
      therapeutic radiopharmaceuticals due to its suitable physico-chemical properties.
      186Re can be produced in several ways, however charged-particle induced reactions
      show to be promising towards no carrier added production. In this work,
      production cross-sections of 186Re were evaluated following the light-charged
      particle induced reactions on tungsten. An effective evaluation technique such as
      Simultaneous Evaluation on KALMAN code combined with least squares concept was
      used to obtain the evaluated data together with covariances. Knowledge of the
      underlying uncertainties in evaluated nuclear data, i.e., covariances are useful
      to improve the accuracy of nuclear data.

PMID- 29448241
TI  - Comprehensive analysis of differentially expressed profiles of Alzheimer's
      disease associated circular RNAs in an Alzheimer's disease mouse model.
AB  - Circular RNAs (circRNAs), a novel kind of non-coding RNA, have received
      increasing attention for their involvement in pathogenesis of Alzheimer's disease
      (AD); however, few studies have reported in the characterization and function of
      AD associated circRNAs. Here the expression profiles of circRNAs in 5- and 10
      month-old SAMP8 mice were identified using circRNA microarray and found that 85
      dysregulated circRNAs were observed in 10-month-old SAMP8 versus control mice and
      231 circRNAs exhibited differential expression in 10-month-old SAMP8 versus 5
      month-old SAMP8. One most significantly dysregulated circRNA, mmu_circRNA_017963,
      was select for Gene Oncology (GO) and pathway analysis. The results showed that
      mmu_circRNA_017963 was strongly related with autophagosome assembly, exocytosis,
      apoptotic process, transport and RNA splicing and highly associated with synaptic
      vesicle cycle, spliceosome, glycosaminoglycan and SNARE interactions in vesicular
      transport pathways. Collectively, this study was the first to describe circRNAs
      expression in different ages of SAMP8 and will contribute to the understanding of
      the regulatory roles of circRNAs in AD pathogenesis and provide a valuable
      resource for the diagnosis and therapy of AD.

PMID- 29448244
TI  - miR-499 Ameliorates Podocyte Injury by Targeting Calcineurin in Minimal Change
      Disease.
AB  - BACKGROUND: Podocyte injury is a hallmark of minimal change disease (MCD).
      Calcineurin inhibitors have been widely used in the current treatment of MCD, and
      miR-499 may target calcineurin. We aimed to study the function of miR-499 in MCD
      and test whether miR-499 delivery can improve MCD. METHODS: An MCD mouse model
      was generated using puromycin aminonucleoside (PAN). MiR-499 was delivered using
      lentiviruses. Biochemical indicators including serum albumin, triglyceride,
      cholesterol, and 24-h urine protein were determined. Targets of miR-499 were
      confirmed using reporter gene activity assays. The ultrastructure of podocytes
      was analyzed using transmission electron microscopy. RESULTS: MiR-499
      significantly improved MCD-related symptoms and signs. Foot-process effacement
      was caused by PAN and partially reversed by miR-499. We identified that both
      CnAalpha and CnAbeta were targets of miR-499, and were overexpressed in the
      presence of PAN. However, miR-499 reduced the expression of CnAalpha and CnAbeta,
      leading to a decreased activity of calcineurin signaling in mouse podocytes in
      vitro and in vivo. In addition, miR-499 recovered PAN-induced reduction of cell
      viability. CONCLUSIONS: MiR-499 ameliorated podocyte injury by targeting CnAalpha
      and CnAbeta in a PAN-induced MCD mouse model. Delivery of miR-499 can be a novel
      strategy for MCD treatment.

PMID- 29448242
TI  - The LncRNA EPEL Promotes Lung Cancer Cell Proliferation Through E2F Target
      Activation.
AB  - BACKGROUND/AIMS: Recent studies have revealed that many long non-coding RNAs
      (lncRNAs) play oncogenic or tumor-suppressive roles in various cancers. Lung
      cancer is the leading cause of cancer-related death worldwide, and many lung
      cancer patients frequently relapse after surgery, even those in the early stages.
      However, the oncogenic or tumor-suppressive roles and clinical implications of
      lncRNAs in lung cancer have not been fully elucidated. METHODS: The association
      between an E2F-mediated cell proliferation enhancing lncRNA (EPEL) expression and
      lung cancer patient survival was accessed using public microarray data with
      clinical information. Cancer-related phenotypes were analyzed by the siRNA
      knockdown of EPEL in two lung cancer cell lines. Gene set analysis of gene
      expression data were performed to identify pathways regulated by EPEL. RNA
      immunoprecipitation, RT-qPCR, and ChIP assays were performed to explore the
      functions of selected target genes regulated by EPEL. RESULTS: EPEL, known as
      LOC90768 and MGC45800, was associated with the relapse and survival of lung
      cancer patients and promoted lung cancer cell proliferation through the
      activation of E2F target genes. EPEL knockdown specifically down-regulated the
      expression of cell cycle-related E2F target genes, including Cyclin B1 (CCNB1),
      in lung cancer cells but not that of apoptosis- or metabolism-related E2F target
      genes. EPEL interacted with E2F1 and regulated the expression of the E2F target
      genes by changing the binding efficiency of E2F1 to the E2F target promoters.
      Moreover, the expression levels of EPEL and CCNB1 both alone and in combination
      were robust prognostic markers for lung cancer. CONCLUSIONS: Considering its
      specific effects on cell cycle-related E2F target genes and its significant
      association with the prognosis of lung cancer patients, we suggest that the
      transcriptional regulation of EPEL through E2F target genes is potentially a
      target for the development of novel therapeutic strategies for lung cancer
      patients.

PMID- 29448243
TI  - Impact of Health Authority Control Measures Aimed at Reducing the Illicit Use of
      Anabolic-Androgenic Steroids.
AB  - OBJECTIVE: To evaluate two interventions on anabolic-androgenic-steroids (AAS)
      dispensation in retail pharmacies. MATERIAL AND METHODS: The study was conducted
      in a north-western region of Spain. Data were the AAS supplied by wholesale drug
      distributors to retail pharmacies over a period of 102 months. It is designed as
      an ecological time-series study; the dependent variables were daily defined doses
      per 1,000 inhabitants per day of each drug. The two interventions evaluated were:
      (1) an inspection program intended for those retail pharmacies where there was an
      irregular dispensation and (2) a regulation put forth forcing these pharmacies to
      carry out additional registers. The medications studied were stanozolol,
      nandrolone, methenolone, testosterone and mesterolone. RESULTS: The pre
      intervention use of AAS displayed a rising trend. There was an immediate
      reduction of 30.56% after the first intervention, and a further reduction of
      35.25% after the second. There was a seasonal pattern of use in the pre
      intervention period, pointing to an increased demand at the end of spring and
      beginning of summer. The most abused drugs were stanozolol and nandrolone.
      CONCLUSION: The health actions were very effective, in that they brought about a
      sharp reduction in the illicit use of AAS. These interventions could be applied
      to other drugs in which abuse were detected.

PMID- 29448245
TI  - Does Endothelin-1 Raise or Lower Blood Pressure in Humans?
AB  - : Subject of Review: Gupta et al. [Cell 2017; 170: 522-533] have shown that a
      genetic variant associated with the 5 vascular diseases is a distal regulator of
      endothelin (ET)-1 gene (EDN1) expression. A common single nucleotide polymorphism
      (SNP) in the third intron of the PHACTR1 gene, rs9349379, is the potential
      variant responsible for increased risk of coronary artery disease, and lower risk
      of migraine, carotid dissection, fibromuscular dysplasia, and hypertension. Since
      ET-1 acts through ET type B receptors (ETBR) on endothelial cells to stimulate
      the production of nitric oxide and prostacyclin and induce vasodilation, this may
      contribute to these findings. Second Opinion: However, ET-1 has been demonstrated
      to play a role in experimental and human hypertension. How can enhanced
      transcription of EDN1 and translation leading to increased production of ET-1 by
      endothelial cells play a role in hypertension despite the availability of data
      that suggest a hypotensive action of ET-1? This could depend on the genetic
      background of individuals. In some humans, the increased ET-1 vasoconstrictor
      action on ETAR and ETBR in vascular smooth muscle might predominate over the
      vasodilator effects exerted via endothelial ETBR, thus resulting in elevated
      blood pressure. CONCLUSION: Alternatively, hypertension could be attributed to
      renal actions of ET-1. Either of these pathophysiological actions may explain a
      hypertensive role of ET-1 despite a lower risk of hypertension associated with
      the G allele at rs9349379, the common SNP in the PHACTR1 gene that is a distal
      regulator of EDN1 and leads to an increased expression of ET-1.

PMID- 29448246
TI  - Effect of Mst1 on Endometriosis Apoptosis and Migration: Role of Drp1-Related
      Mitochondrial Fission and Parkin-Required Mitophagy.
AB  - BACKGROUND/AIMS: Mitochondrial homeostasis is implicated in the development and
      progression of endometriosis through poorly defined mechanisms. Mst1 is the major
      growth suppressor related to cancer migration, apoptosis and proliferation.
      However, whether Mst1 is involved in endometriosis apoptosis and migration via
      regulating the mitochondrial function remains to be elucidated. METHODS:
      Expression of Mst1 in endometriosis was examined via western blots. Cellular
      apoptosis was detected via MTT and TUNEL assay. Gain of function assay about Mst1
      was conducted via adenovirus over-expression. Mitochondrial functions were
      evaluated via mitochondrial membrane potential JC-1 staining, ROS flow cytometry
      analysis, mPTP opening assessment and immunofluorescence of HtrA2/Omi. The
      mitophagy activity were examined via western blots and immunofluorescence.
      RESULTS: First, we found that Mst1 was significantly downregulated in the ectopic
      endometrium of endometriosis compared to the normal endometrium. However, the
      recovery of Mst1 function was closely associated with the inability of
      endometrial stromal cells (ESCs) to migrate and survive. A functional study
      indicated that regaining Mst1 enhanced Drp1 post-transcriptional phosphorylation
      at Ser616 and repressed Parkin transcription activity via p53, leading to
      mitochondrial fission activation and mitophagy inhibition. Excessive Drp1-related
      fission forced the mitochondria to liberate HtrA2/Omi into the cytoplasm.
      Moreover, Mst1-induced defective mitophagy evoked cellular oxidative stress,
      energy metabolism and calcium overload. Through excessive mitochondrial fission
      and aberrant mitophagy, Mst1 launched caspase 9-related mitochondrial apoptosis
      and abrogated F-actin/lamellipodium-dependent cellular migration. Notably, we
      also defined NR4A/miR181c as the upstream signal for Mst1 dysfunction in
      endometriosis. CONCLUSION: Collectively, our results comprehensively described
      the important role of the NR4A-miR181c-Mst1 pathway in endometriosis, which
      handled mitochondrial apoptosis and F-actin/ lamellipodium-based migration via
      the regulation of Drp1-related mitochondrial fission and Parkin-required
      mitophagy, with a potential application in endometriosis therapy by limiting ESCs
      migration and promoting apoptosis.

PMID- 29448247
TI  - Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to
      Inhibit Human Renal Cell Carcinoma Cells.
AB  - BACKGROUND/AIMS: Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin
      ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6
      expression and potential function in renal cell carcinoma (RCC). METHODS: MAGEA6
      and AMPK expression in human RCC tissues and RCC cells were tested by Western
      blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in
      human RCC cells. Cell survival and proliferation were tested by MTT assay and
      BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and
      single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was
      established to test RCC cell growth in vivo. RESULTS: MAGEA6 is specifically
      expressed in RCC tissues as well as in the established (786-O and A498) and
      primary human RCC cells. MAGEA6 expression is correlated with AMPKalpha1
      downregulation in RCC tissues and cells. It is not detected in normal renal
      tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted
      shRNA induced AMPK stabilization and activation, which led to mTOR complex 1
      (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by
      AMPKalpha1 shRNA or the dominant negative AMPKalpha1 (T172A), almost reversed
      MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the
      constitutive-active AMPKalpha1 (T172D) mimicked the actions by MAGEA6 shRNA. In
      vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice
      than the control tumors. AMPKalpha1 stabilization and activation as well as
      mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. CONCLUSION:
      MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling.

PMID- 29448248
TI  - LncRNA GAS5 Overexpression Reverses LPS-Induced Inflammatory Injury and Apoptosis
      Through Up-Regulating KLF2 Expression in ATDC5 Chondrocytes.
AB  - BACKGROUND/AIMS: Osteoarthritis (OA) is the most frequently occurring joint
      disease and characterized by degeneration of cartilage. As the unique cell type
      in cartilage, chondrocytes play a crucial role during OA. Our study explored the
      influence of long non-coding RNA (lncRNA) growth arrest-specific transcript 5
      (GAS5) on lipopolysaccharides (LPS)-induced injury in ATDC5 cells. METHODS: Cell
      viability, apoptosis and expression of inflammatory cytokines were all assessed
      to evaluate LPS-induce inflammatory injury. Expression of GAS5 in LPS-induced
      cells was evaluated by qRT-PCR. After cell transfection, effect of abnormally
      expressed GAS5 on LPS-induced inflammatory injury was determined. Then, the
      possible target of GAS5 was screened by bioinformatics and verified by qRT-PCR
      and luciferase activity assay. Together, whether aberrant expression of target
      gene affected the modulation of GAS5 in LPS-induced inflammatory injury was also
      assessed. Finally, the influences of aberrant expressed Kruppel-like factor 2
      (KLF2) on nuclear factor kappaB (NF-kappaB) and Notch pathways were detected by
      Western blot analysis. RESULTS: LPS reduced cell viability and promoted cell
      apoptosis and secretion of inflammatory cytokines, along with down-regulation of
      GAS5. LPS-induced injury was alleviated by GAS5 overexpression while was
      exacerbated by GAS5 silence. KLF2 was predicted and verified as a target of GAS5,
      and GAS5 functioned through regulating expression of KLF2. Besides, aberrant
      expression of KLF2 regulated expressions of key kinases involved in the NF-kappaB
      and Notch pathways. CONCLUSION: GAS5 might ameliorate LPS-induced inflammatory
      injury in ATDC5 chondrocytes by inhibiting the NF-kappaB and Notch signaling
      pathways.

PMID- 29448249
TI  - The Placental Secretome: Identifying Potential Cross-Talk Between Placenta and
      Islet beta-Cells.
AB  - BACKGROUND/AIMS: Insulin-secreting islet beta-cells adapt to the insulin
      resistance associated with pregnancy by increasing functional beta-cell mass, but
      the placental signals involved in this process are not well defined. In the
      current study, we analysed expression of G-protein coupled receptor (GPCR) mRNAs
      in mouse islets and islet GPCR ligand mRNAs in placenta during pregnancy to
      generate an atlas of potential interactions between the placenta and beta-cells
      to inform future functional studies of islet adaptive responses to pregnancy.
      METHODS: Quantative RT-PCR arrays were used to measure mRNA expression levels of:
      (i) 342 GPCRs in islets from non-pregnant mice, and in islets isolated from mice
      on gestational days 12 and 18; (ii) 126 islet GPCR ligands in mouse placenta at
      gestational days 12 and 18. RESULTS: At gestational day 12, a time of rapid
      expansion of the beta-cell mass, 189 islet GPCR mRNAs were quantifiable, while 79
      of the 126 known islet GPCR ligand mRNAs were detectable in placental extracts.
      Approximately half of the quantifiable placental GPCR ligand genes were of
      unknown function in beta-cells. The expression of some islet GPCR and placental
      ligand mRNAs varied during pregnancy, with altered expression of both GPCR and
      ligand mRNAs by gestational day 18. CONCLUSION: The current study has revealed
      numerous potential routes for interaction between the placenta and islets, and
      offers an atlas to inform further functional studies of their roles in adaptive
      responses to pregnancy, and in the regulation of the beta-cell mass.

PMID- 29448250
TI  - Overexpression of Lymphocyte Antigen 6 Complex, Locus E in Gastric Cancer
      Promotes Cancer Cell Growth and Metastasis.
AB  - BACKGROUND/AIMS: Lymphocyte antigen 6 complex, locus E (LY6E) is a member of the
      lymphostromal cell membrane Ly6 superfamily protein. The present study
      investigated the clinical significance and potential biological function of LY6E
      in gastric cancer (GC). METHODS: LY6E mRNA and protein expressions in human GC
      tissues and GC cells were tested. Relationship between LY6E expression and the GC
      patients' clinicopathologic characteristics was analyzed. LY6E was silenced by
      siRNA in the cultured GC cells. RESULTS: The RNA expression microarray profiling
      assay results demonstrated that LY6E mRNA was significantly increased in multiple
      human GC tumor tissues. Immunohistochemistry (IHC) staining analysis revealed
      that 59 of 75 (78.7%) GC specimens were LY6E positive. LY6E over-expression in
      human GC was correlated with the histology grade, AJCC stage, N classification,
      lymphatic invasion, and tumor location. Notably, functional LY6E expression was
      also detected in AGS and other established GC cell lines. LY6E knockdown by
      targeted-siRNA inhibited AGS cell survival and proliferation. Meanwhile, the LY6E
      siRNA induced G1-S cell cycle arrest and apoptosis in AGC cells. Additionally,
      AGC cell migration was also inhibited by LY6E knockdown. Expressions of tumor
      suppressing proteins, including PTEN (phosphatase and tensin homolog) and E
      Cadherin, were increased in LY6E-silenced AGS cells. CONCLUSION: LY6E over
      expression in GC is potentially required for cancer cell survival, proliferation
      and migration.

PMID- 29448252
TI  - Functions and Roles of Long-Non-Coding RNAs in Human Nasopharyngeal Carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is one of the most common cancers originating in
      the nasopharynx and occurring at high frequency in South-eastern Asia and North
      Africa. Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA
      molecules and key regulators of developmental, physiological, and pathological
      processes in humans. Emerging studies have shown that lncRNAs play critical roles
      in tumorgenicity and cancer prognosis. With the development of deep sequencing
      analyses, an extensive amount of functional lncRNAs have been discovered in
      nasopharyngeal carcinoma tissues and cell lines. However, the roles and
      mechanisms of aberrantly expressed lncRNAs in the pathogenesis of NPC are not
      fully understood. In this review, we briefly illustrate the concept,
      identification, functional characterization, and summarize recent advancements of
      biological functions of lncRNAs with heterogeneous mechanistic characterization
      and their involvement in NPC. Then, we describe individual lncRNAs that have been
      associated with tumorgenesis, growth, invasion, cancer stem cell differentiation,
      metastasis, drug resistance and discuss the strategies of their therapeutic
      manipulation in NPC. We also review the emerging insights into the role of
      lncRNAs and their potential as biomarkers and therapeutic targets for novel
      treatment paradigms. Finally, we highlight the up-to-date of clinical information
      involving lncRNAs and future directions in the linking lncRNAs to potential gene
      therapies, and how modifications of lncRNAs can be exploited for prevention and
      treatment of NPC.

PMID- 29448251
TI  - Expression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Human
      Epicardial and Intramyocardial Coronary Arteries of Male Patients Undergoing
      Coronary Artery Bypass Grafting.
AB  - OBJECTIVES: Atherosclerosis is almost absent in intramyocardial coronary
      arteries, while epicardial coronary arteries may show extensive occlusive
      disease. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)
      expression has been implicated in atherogenesis. We aimed to investigate
      differences in arterial wall LOX-1 expression between human epicardial and
      intramyocardial coronary arteries. METHODS: Epicardial and intramyocardial total
      artery wall specimens were obtained from 13 male patients (aged 61.9 +/- 10.3
      years) undergoing coronary artery bypass graft surgery due to 3-vessel coronary
      artery disease. LOX-1 expression was examined by reverse transcription-polymerase
      chain reaction. RESULTS: LOX-1 expression was significantly higher in the
      arterial wall of epicardial coronary arteries compared to intramyocardial
      coronary arteries. The LOX-1/GAPDH ratio was 0.48 +/- 0.07 vs. 0.35 +/- 0.03 (p <
      0.001). CONCLUSIONS: Our findings may partially explain the atheroprotective
      effect of the intramyocardial course since arterial wall LOX-1 expression was
      lower in intramyocardial arteries and higher in epicardial coronary arteries.

PMID- 29448253
TI  - Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral
      Disc Degeneration by Inhibiting NF-kappaB Signalling Pathway.
AB  - BACKGROUND/AIMS: Cartilaginous endplate (CEP) degeneration is an important cause
      for intervertebral disc (IVD) degeneration that leads to low-back pain. The
      identification of compounds that may prevent CEP degeneration is of interest for
      the prevention of IVD degeneration. METHODS: Catabolic protease expression in the
      CEP of disc degeneration patients was first assessed. The toxicity, function and
      underlying mechanism of lycorine (LY) on CEP-derived chondrocytes degeneration
      were assessed in vitro by flow cytometry analysis and western blotting. The
      concentration and function of LY in rat-tail disc-degeneration models were also
      assessed by HPLC (High Performance Liquid Chromatography) quantification and
      histological analysis. RESULTS: In CEP cells, Interleukin (IL)-1beta upregulated
      the expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and
      metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 that is
      critical for the degradation of cartilage extracellular matrix. Interestingly, LY
      suppressed the expression of these enzymes via the inhibition of nuclear factor
      kappaB (NFkappaB) signalling and thus prevented IL-1beta-induced endplate cell
      degeneration in vitro. More importantly, LY also reduced the expression of MMP-3,
      MMP-13, ADAMTS-4 and ADAMTS-5 in CEP and exerted a protective effect on both CEP
      and nucleus pulposus (NP) degeneration. In addition to its inhibitory effect on
      matrix-degrading protease expression, LY treatment also reduced positive
      regulators of proinflammatory cytokines, such as MIF, which can be secreted by
      CEP cells and subsequently target NP cells. CONCLUSION: LY could serve as a
      potential drug for treating IVD disease.

PMID- 29448254
TI  - Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear
      Cells from Active Tuberculosis Patients.
AB  - BACKGROUND/AIMS: Dysregulated expression of circular RNAs (circRNAs) was
      demonstrated to be implicated in many diseases. Here, we aimed to determine
      circRNA profile in peripheral blood mononuclear cells (PBMCs) from active
      tuberculosis (TB) patients to identify novel biomarkers for TB. METHODS:
      Expression profile of circRNAs in PBMCs from 3 active pulmonary TB patients and 3
      healthy controls were analyzed by microarray assay. Six circRNAs were selected
      for validation using real time-quantitative PCR (qRT-PCR) in 40 TB patients and
      40 control subjects. Receiver operating characteristic (ROC) curve was
      constructed to evaluate their values in TB diagnosis. Hsa_circRNA_001937 was
      chosen for further evaluation in an independent cohort consisting of 115 TB, 40
      pneumonia, 40 COPD, 40 lung cancer patients and 90 control subjects. An eight
      month follow up was performed in 20 newly diagnosed TB patients to investigate
      the expression change of hsa_circRNA_001937 after chemotherapy. RESULTS: We
      revealed and confirmed that a number of circRNAs were dysregulated in TB
      patients. Of the six studied physio circRNAs, the levels of hsa_circRNA_001937,
      hsa_circRNA_009024 and hsa_ circRNA_005086 were significantly elevated and
      hsa_circRNA_102101, hsa_circRNA_104964 and hsa_circRNA_104296 were significantly
      reduced in PBMCs from TB patients as compared to healthy controls. ROC curve
      analysis suggested that hsa_circRNA_001937 has the largest area under the curve
      (AUC = 0.873, P<0.001). Hsa_circRNA_001937 was significantly increased in
      patients with TB compared with patients with pneumonia, COPD and lung cancer.
      Hsa_ circRNA_001937 was correlated with TB severity (r = 0.4053, P = 0.010) and
      its expression significantly decreased after treatment. CONCLUSION: This study
      identified a set of deregulated circRNAs in active TB PBMCs, our data also
      suggest that hsa_circRNA_001937 can be used as a potential diagnostic biomarker
      of TB.

PMID- 29448255
TI  - Intrathecal Administration of CXCL1 Enhances Potassium Currents in Microglial
      Cells.
AB  - The functioning of microglial cells inside the central nervous system depends on
      their ion channels expression. Microglia are capable of synthesizing different
      cytokines and chemokines, including CXCL1, and responding to their action via
      specific receptors. In this study, we explore the effect of intrathecal injection
      of CXCL1 on potassium currents, expressed in CX3CR1-Green Fluorescent Protein
      labeled microglia in transgenic mice. The results showed that CXCL1
      hyperpolarized the cells by enhancing inward rectifying potassium currents and
      increasing the membrane area, suggesting an activating effect on microglia.

PMID- 29448256
TI  - Serum Levels of FGF21 and Prediction of Cardiovascular Events.

PMID- 29448257
TI  - Nonbacterial Thrombotic Endocarditis Presenting with Leg Pain and a Left Atrial
      Mass Lesion.
AB  - Systemic lupus erythematosus (SLE) is a major cause of nonbacterial thrombotic
      endocarditis (NBTE) associated with intracardiac sterile vegetations. It is rare
      for vegetations to present as an atrial tumor. This report describes a 48-year
      old female with SLE and antiphospholipid syndrome complicated by recurrent
      thrombosis on anticoagulation. A large left atrial mass lesion was detected on
      echocardiography during a work-up for leg burning. Infective endocarditis could
      not be confirmed, and hence left atrial mass lesion was the most likely
      diagnosis. The patient was managed surgically and the pathology report revealed
      fibrin networks in a pattern similar to that of thrombosis, characteristic of
      NBTE.

PMID- 29448258
TI  - Altered Long Noncoding RNA and Messenger RNA Expression in Experimental
      Intracerebral Hemorrhage - a Preliminary Study.
AB  - BACKGROUND/AIMS: Functional recovery in the chronic phase is a difficult problem
      in intracerebral hemorrhage (ICH) treatment. Long noncoding RNAs (lncRNAs) are
      demonstrated to be involved in central nervous system (CNS) disorders. However,
      the roles of lncRNAs in post-ICH injury and repair are poorly understood,
      especially those that may be attributed to long-term neurological deficit. The
      present study depicted the lncRNA and messenger RNA (mRNA) profile by microarray
      at late stage after an experimental ICH. METHODS: LncRNA and mRNA microarray was
      used to first identify differentially expressed genes. Gene ontology (GO) and the
      Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to
      determine bio-functions and signaling pathways, with which differentially
      expressed genes are most closely related. Quantitative real-time polymerase chain
      reaction (PCR) was used to validate the results of microarray. Finally, the
      lncRNA-mRNA co-expression network was constructed to find the interaction of
      genes. RESULTS: A total of 625 differentially expressed lncRNAs and 826 expressed
      mRNAs were identified. Altered genes were enriched in mitochon-drial matrix, G
      protein coupled receptor signaling pathway, and olfactory transduction, which may
      be associated with ICH-induced pathophysiologic changes in the long term. A co
      expression network profile based on 5 validated differentially expressed lncRNAs
      and 205 interacted mRNAs was composed of 210 nodes and 298 connections.
      CONCLUSION: Mitochondrial matrix, reduced G-protein coupled receptor activity,
      and impaired olfactory transduction may be involved in the sequelae following
      ICH. Further, these dysregulated lncRNAs and mRNAs may be the promising
      therapeutic targets to overcome obstacles in functional recovery following ICH.

PMID- 29448259
TI  - Applicability of Computerized Planimetric Method in Estimating Plaque
      Accumulation and Efficacy of a Cleaning Method for Removable Dental Prostheses.
AB  - PURPOSE: To demonstrate how data collected using the computerized planimetric
      method (CPM) can be analyzed by providing an example in which the amount of
      plaque accumulation and the efficacy of the rotating needles device (RND) in
      cleaning specific parts of partial removable dental prostheses (PRDPs) were
      estimated. MATERIALS AND METHODS: Thirty-four participants wearing a total of 41
      double-crown-retained PRDPs with veneered secondary crowns were included in this
      study. The PRDPs underwent the following steps: preparing the PRDP for
      photography, photography of the PRDP, cleaning the PRDP with the RND, and re
      photography. One trained examiner used a tested CPM to analyze 98 images (49
      before/49 after). Each participant was considered as a statistical unit; thus, if
      the participant had two PRDPs, one was randomly selected for analysis.
      Reliability was tested using intraclass correlation coefficients (ICCs[1, 2]),
      and nonparametric Wilcoxon signed rank test was used for all comparisons.
      RESULTS: The intraclass correlation coefficients (images before/after) for both
      the base and veneer were > 0.9. Wilcoxon signed rank test P value was < .001 for
      the comparison of plaque accumulation on the base and veneer, estimating the
      RND's efficacy on both PRDP parts (before/after) and comparing the RND's efficacy
      on the base and the RND's efficacy on the veneer. CONCLUSIONS: There are
      different ways to analyze data collected via CPM; thus, it is advisable to
      provide an explanation for the choice of modeling. Plaque accumulation was
      significantly greater on the double-crown veneer than on the base. The RND
      efficacy in cleaning the veneer and the base is significant, but more substantial
      in cleaning the base.

PMID- 29448260
TI  - Effect of Coloring of Zirconia Framework and Ceramic Veneer on Adhesion of
      Interfacial Surfaces Determined Using Three-Point Flexural Bonding Strength: An
      In Vitro Study.
AB  - PURPOSE: The aim of this study was to investigate the effect of coloring on the
      interfacial surface adhesion between a zirconia framework and ceramic veneer
      using three-point flexural bonding strength. MATERIALS AND METHODS: A total of 40
      zirconia bars (Zirlux ST1; DE Healthcare) were cut and divided into two groups of
      20 (Groups 1 and 2). The two groups were then further split and divided into four
      groups of 10 each (Groups 1a, 1b, 2a, and 2b). Groups 1a and 1b tested adhesion
      of uncolored zirconia and two different shades of ceramic veneer, and Groups 2a
      and 2b tested adhesion of zirconia colored with two different coloring liquids
      and one shade of ceramic veneer. RESULTS: Some coloring liquids used to color
      zirconia can significantly affect the bond strength between zirconia and the
      veneer, whereas ceramic veneer shades do not influence adhesion. CONCLUSION:
      Bonding strength between zirconia framework and ceramic veneer is affected by the
      coloring of the zirconia.

PMID- 29448261
TI  - Effects of Impression Material, Impression Tray Type, and Type of Partial
      Edentulism on the Fit of Cobalt-Chromium Partial Denture Frameworks on Initial
      Clinical Insertion: A Retrospective Clinical Evaluation.
AB  - PURPOSE: To evaluate the effects of impression material, impression tray type,
      and type of partial edentulism (ie, Kennedy class) on the accuracy of fit of
      cobalt-chromium (Co-Cr) partial removable dental prostheses (PRDP) in terms of
      the number of fabricated frameworks required until the attainment of adequate
      fit. MATERIALS AND METHODS: Electronic case documentations of 120 partially
      edentulous patients provided with Co-Cr PRDP treatment for one or both arches
      were examined. Statistical analyses of data were performed using analysis of
      variance and Tukey honest significant difference test to compare the
      relationships between the different factors and the number of frameworks that
      needed to be fabricated for each patient (alpha = .05). RESULTS: Statistical
      analysis of data derived from 143 records (69 maxillary and 74 mandibular)
      revealed no significant correlation between impression material, tray type, or
      Kennedy class and the number of construction attempts for the pooled or
      individual arch data (P >= .05). CONCLUSION: In PRDP treatment, alginate can be
      chosen as a first-choice material, and metal stock trays can be a preferred
      option for making final impressions to fabricate Co-Cr frameworks.

PMID- 29448262
TI  - Assessment of Location of the Mandibular Canal: Correlation Between Panoramic and
      Cone Beam Computed Tomography Measurements.
AB  - PURPOSE: To compare panoramic and cone beam computed tomography (CBCT)
      determinations of implant-to-mandibular canal (MC) dimensions in mandibular
      regions posterior to the mental foramen and to investigate whether factors such
      as gender, age, region, and vertical dimension influence correlation between the
      two techniques. MATERIALS AND METHODS: A retrospective analysis was carried out
      in 64 consecutive adult patients (42 females, 22 males; average age 57.1 +/- 13.3
      years) in whom 126 implants were positioned in the posterior segment of the
      mandible. Implant sites (first premolar, second premolar, first molar, and second
      molar) were assessed on each panoramic and CBCT radiograph by measuring the
      distance from the inferior border of the implant to the superior border of the
      MC. Binary logistic regression analysis was used to compute the odds ratios (ORs)
      of each implant site for underestimation vs nonunderestimation. Linear regression
      analysis was performed with CBCT dimension as the dependent variable and
      panoramic dimension, gender, and age as the independent variables. RESULTS: The
      mean implant-to-MC dimension was 2.50 +/- 1.31 mm in panoramic radiography and
      2.91 +/- 1.62 mm in CBCT. The OR that an implant at the second molar region
      belonged to the underestimation group was strong (15.1:1) and highly significant
      (P = .011). If a predictive value of .95 was demanded, the implant-to-MC
      dimensions had to be overestimated by 2 mm compared to the predicted CBCT
      dimension. CONCLUSION: This study provides evidence of an underestimation of
      available vertical bone dimensions for implants in the posterior regions of the
      mandible when assessed by panoramic radiography. Use of CBCT is therefore
      recommended for all implant size estimations in this region.

PMID- 29448263
TI  - Comparison of Coronal Tooth Reductions Resulting from Different Crown
      Preparations.
AB  - PURPOSE: The aim of this study was to quantify the coronal tooth structure
      reductions (CTSRs) resulting from a variety of different types of crown
      preparations performed by undergraduate dental students in a simulation clinic
      teaching program. MATERIALS AND METHODS: A total of 76 students each submitted 21
      different crown preparations completed on typodont teeth, which were individually
      weighed and analyzed in relation to whole and sectioned reference teeth to
      calculate the CTSR resulting from each preparation. RESULTS: The largest CTSR
      resulted from preparations for porcelain bonded to zirconia crowns (50.6%),
      followed by those for porcelain bonded to metal (PBM) crowns (44.3%), PBM fixed
      partial dentures (32.8%), shell crowns (32.5%), and full gold crowns (24.6%).
      CONCLUSION: A wide range of CTSRs resulted from the different types of crown
      preparations investigated in this study. The crown preparations performed by the
      undergraduate students produced more conservative coronal reductions than
      comparable crown preparations generated under controlled in vitro conditions.

PMID- 29448264
TI  - Clinical Appraisal of the WAM'X Super Quick Post-and-Core Removal Device.
AB  - This report describes an innovative technique to remove post-and-core
      restorations. The WAM'X Super Quick post removal device permits a secure
      mechanical traction technique that can adapt to variable root angulations.
      Pivoting prongs mounted on forceps allow post removal while preserving the
      ferrule effect to improve resistance to fractures.

PMID- 29448265
TI  - Short-term Postoperative Pain and Swelling Associated with Mini and Standard-Size
      Implants in the Same Patients.
AB  - PURPOSE: To assess short-term postoperative pain and swelling after insertion of
      mini dental implants (MDI) and standard-size implants (SSI) in the same patients
      at different times. MATERIALS AND METHODS: A convenience sample of 42 patients
      (22 females, 20 males; 58 to 73 years old) participated. Half of the participants
      received MDIs first, and the other half received SSIs first. Self-perceived pain
      and swelling at 1, 3, 5, 7, and 10 days postoperative were assessed using a 0-10
      visual analog scale. RESULTS AND CONCLUSION: Flapless MDI insertion led to
      significantly less intense postoperative pain, less intake of analgesics, and
      almost no swelling compared to SSI insertion.

PMID- 29448266
TI  - Zirconia-Reinforced Framework for Maxillary Complete Dentures.
AB  - PURPOSE: This study introduces a newly developed zirconia complete denture (ZrD)
      that incorporates a ceria-stabilized zirconia/alumina nano-composite framework
      fabricated with computer-aided design/computer-aided manufacture (CAD/CAM).
      MATERIALS AND METHODS: Twenty-nine edentulous patients received either a
      maxillary ZrD (n = 10) or a maxillary conventional complete denture (CD) (n =
      19). Patient satisfaction was evaluated before and 12 months after prosthesis
      placement using the McGill Denture Satisfaction Instrument. RESULTS: During
      follow-up periods of up to 2 years, no denture fractures were found in the ZrD or
      CD group. All aspects of patient satisfaction improved, and no significant group
      differences were found. CONCLUSION: Within the limitations of this study, it can
      be concluded that maxillary complete dentures with nano-zirconia frameworks might
      be an alternative prosthetic treatment option.

PMID- 29448267
TI  - A Novel Computer-Aided Design/Computer-Assisted Manufacture Method for One-Piece
      Removable Partial Denture and Evaluation of Fit.
AB  - PURPOSE: To investigate a computer-aided design/computer-aided manufacturing
      (CAD/CAM) process for producing one-piece removable partial dentures (RPDs) and
      to evaluate their fits in vitro. MATERIALS AND METHODS: A total of 15 one-piece
      RPDs were designed using dental CAD and reverse engineering software and then
      fabricated with polyetheretherketone (PEEK) using CAM. The gaps between RPDs and
      casts were measured and compared with traditional cast framework RPDs. RESULTS:
      Gaps were lower for one-piece PEEK RPDs compared to traditional RPDs. CONCLUSION:
      One-piece RPDs can be manufactured by CAD/CAM, and their fits were better than
      those of traditional RPDs.

PMID- 29448273
TI  - ?

PMID- 29448274
TI  - ?

PMID- 29448275
TI  - ?

PMID- 29448276
TI  - ?

PMID- 29448277
TI  - ?

PMID- 29448278
TI  - ?

PMID- 29448279
TI  - ?

PMID- 29448280
TI  - ?

PMID- 29448281
TI  - [Evaluation of Factor Structure and Construct Validity of the 12-Item Short
      Version of the OPD Structure Questionnaire (OPD-SQS) in Psychosomatic Patients].
AB  - BACKGROUND: Screening for personality dysfunction is regarded as increasingly
      important for treatment planning in clinical settings as this allows to determine
      specific clinical pathways in an early stage. Recently, the 12-item OPD Structure
      Questionnaire (OPD-SQS) was developed for this purpose and initial results of the
      factor structure and validity have been published. This study aimed to
      investigate and validate the OPD-SQS in further patient samples beyond the team
      of developers and to provide reference values. METHODS: Data was assessed in
      psychosomatic outpatients (N=565) and inpatients (N=670) at Charite -
      Universitatsmedizin Berlin between 2012 and 2016. To examine the factor structure
      of the OPD-SQS confirmatory factor analyses (CFA) were applied in both samples.
      To evaluate construct validity, a SKID-II-Interview was performed in N=105
      patients and narcissism inventory (NI-90) was completed by N=160 patients. In
      addition, a range of instruments reflecting emotional, social and physical health
      were assessed. Bivariate correlations were performed to analyze relations between
      these instruments and the OPD-SQS. RESULTS: CFAs indicated a good to satisfying
      fit for the proposed model including 3 factors. A Bifactormodel resulted in very
      good modelfit. Analyses of construct validity resulted in high positive
      correlations of OPD-SQS with dimensional SCID-II scores, SKID-II interviews, and
      NI-90 confirming convergent validity. Results for discriminant validity were
      heterogeneous. Medium to high correlations were found with a range of instruments
      including D-CAT (depression), A-CAT (anxiety), S-CAT (stress), and PHQ-15
      (somatic symptoms). Subsequent analyses revealed, that the factor self-perception
      is potentially being influenced by current depression and anxiety. Analyses
      showed only minor differences of correlations between OPD-SQS subscales and other
      instruments. CONCLUSIONS: The OPD-SQS seems to be appropriate for screening of
      personality dysfunction. However, other aspects of psychopathology are gathered
      in addition. Therefore, further investigation of the patients' personality
      structure such as an OPD interview may be added in clinical settings.

PMID- 29448282
TI  - [Significance of Helicobacter pylori Diagnostic in Glaucoma].
AB  - Glaucoma is one of the most common causes for blindness worldwide. Even if some
      risk factors for this disease are known, like increased intraocular pressure or
      increased age, its pathomechanism is still not fully understood. Multiple studies
      recently analyzed the role of a Helicobacter pylori infection in the glaucoma
      pathogenesis. Several studies showed a correlation, while others did not come to
      this conclusion. In summary, it is very likely that a Helicobacter pylori
      infection coincides with an increased risk for a primary open-angle or normal
      tension glaucoma. Still, larger studies, with strict inclusion and exclusion
      criteria, as well as age-matched control groups, are needed to find out if a
      Helicobacter pylori infection really leads to a higher risk for glaucoma.

PMID- 29448283
TI  - [Significance of Endothelin-1 in Glaucoma - a Short Overview].
AB  - This review article is focused on the various facets of possible endothelin's
      role in glaucoma; involvement of endothelin in other ocular, in particular
      vascular, diseases is not specifically discussed. Endothelin is an ubiquitous
      molecule that occurs in practically all ocular tissues. Its primary physiological
      function is regulation of the blood vessel diameter and hence regulation of the
      blood supply in tissues. It is secreted locally, and exerts its effect also
      predominantly locally. This limits the value of venous blood sampling for
      estimation of the endothelin function in a particular patient, or in study
      cohorts as well. Endothelin is involved in the regulation of intraocular
      pressure, in the regulation of blood flow and in activation of retinal and optic
      nerve head astrocytes. All these functions are of high importance when it comes
      to pathogenesis of glaucoma. Possible future directions for glaucoma treatment
      should encompass pharmacological antagonism to endothelin, an avenue which is at
      present hindered by potentially serious side-effects of available endothelin
      antagonists.

PMID- 29448284
TI  - [The Keyrole of Multiomics in the Predictive, Preventive and Personalised Medical
      Approach towards Glaucoma Management].
AB  - Glaucoma is the second leading cause of blindness, with altogether about 70
      million patients registered worldwide. These facts prompt us to reconsider
      currently applied concepts in overall glaucoma management. Innovative strategies
      of predictive, preventive and personalised medicine (PPPM) are expected to
      considerably improve disease prevention and personalised treatment. The
      comprehensive PPPM measures include the application of individualised patient
      profiles, "phenotyping", molecular characterisation of the pre-lesions and
      disease stages, innovative screening programs, patient stratification, early and
      predictive diagnosis, targeted prevention, and the creation of personalised
      treatment algorithms. The main stakeholders are glaucoma-dedicated researchers,
      ophthalmologists, general practitioners, groups at risk, specialised medical
      units, affected patients and their family members, insurances, policy makers, and
      the diagnostic and pharmaceutical industries. Potential beneficiaries include
      these groups as well as society as a whole, due to financial savings in the
      healthcare expected.

PMID- 29448285
TI  - [Risk Factors and Therapeutic Goals for Primary and Secondary Cardiovascular
      Prevention: Significance for the Glaucoma Patient].
AB  - Hypertension, diabetes mellitus and dyslipidaemia are among the most important
      cardiovascular risk factors. In addition, there is an association with the
      development and progression of glaucoma. During the last years, there has been an
      intense discussion concerning optimal treatment goals for these risk factors.
      Recently, the American Heart Association has defined a blood pressure greater
      than 130/80 mmHg as hypertension and the European guidelines will follow this
      definition. These lower blood pressure limits increase the risk for a too strict
      blood pressure treatment with night values, which might be too low for glaucoma
      patients. In contrast, the treatment goals for LDL cholesterol should be as low
      as possible ("the lower the better"). There is a more differentiated picture
      concerning treatment goals for diabetes mellitus. For elderly patients, which is
      the main group of the glaucoma patients, a less intense blood sugar reduction is
      currently recommended with an HbA1c value of above 7%. The present paper
      summarizes the significance of cardiovascular risk factors and the respective
      treatment goals for the therapy of patients with glaucoma.

PMID- 29448286
TI  - [Mitochondrial Dysfunctions and Role of Coenzyme Q10 in Patients with Glaucoma].
AB  - Mitochondrial function is closely linked to numerous aspects of eye health.
      Imbalance between the creation of energy and the development of reactive oxygen
      species (ROS) seems to be the cause of the development of mitochondrial
      dysfunctions. As a result of this energy deficit, the level of oxidative stress
      in the eye tissues increases, leading to numerous ophthalmic impairments. It is
      important to distinguish between primary mitochondrial eye diseases and secondary
      mitochondrial changes. Primary mitochondrial eye diseases, for example Leber's
      hereditary optic atrophy (LHON), retinitis pigmentosa and chronic progressive
      external ophthalmoplegia are caused by direct damage to mitochondrial function
      induced by defective genes, either located on mitochondrial DNA (mtDNA) or the
      DNA of the nucleus (nDNA). In contrast, secondary mitochondrial dysfunctions are
      caused by environmental factors. In recent years, there has been growing evidence
      that mitochondrial dysfunctions play an important role in many common eye
      diseases, such as glaucoma, dry eye, diabetic retinopathy, cataract and age
      related macular degeneration (AMD). This article summarises current knowledge of
      mitochondrial dysfunctions and the role of coenzyme Q10 (CoQ10) as a possible
      treatment option - with a special focus on glaucoma.

PMID- 29448287
TI  - [Significance of Homocysteine in Glaucoma].
AB  - Endothelial dysfunction and vascular dysregulation play a role in the
      multifactorial pathogenesis of glaucomatous optic nerve atrophy.
      Hyperhomocysteinemia is a risk factor for endothelial dysfunction and is
      associated with primary open-angle glaucoma as well as secondary open-angle
      glaucoma in the pseudoexfoliation syndrome. This paper reviews the literature on
      the association between homocysteine metabolism and glaucomatous disease and
      explains the possible role of hyperhomocysteinemia in the pathogenesis and
      progression of glaucoma. We discuss the role of exogenous modifiable risk factors
      for the prevention and therapy of glaucoma, as well as modification of these
      factors by changes in life style, such as weight reduction, changes in nutrition
      and physical activity. The roles of homocysteine in regulating the extracellular
      matrix, vasotoxicity, neurodegeneration, and epigenetics are explained.
      Prevention and therapy of glaucoma by regulation of homocysteine levels are
      discussed.

PMID- 29448288
TI  - [APD in First Graders. Which tests discriminate between normal and impaired
      children?]
AB  - OBJECTIVE: In a controlled group comparison it was shown for 2nd, 3th and 4th
      graders that children with auditory processing disorders (APD) could be
      distinguished from those without (Non-APD) by three to four diagnostic tools. The
      hit rate was 93.6 % resp. 97.5 % 1, 2. The current study investigated whether
      such a separation is also possible in first graders. MATERIAL AND METHODS:
      Performance of 77 first graders in two clinically and diagnostically confirmed
      groups (n = 40 with APD, mean age: 6.93, SD 0.53 yrs; n = 37 Non APD, mean age:
      6.90, SD 0.52 yrs) in 8 auditory processing tests of an eclectic test battery
      were compared (Dichotic Words Test; Phoneme Discrimination and Phoneme
      Identification; Word-Understanding in Background Noise; Binaural Summation Word
      Test; Sound Blending; Auditory Sequential Memory of Digits; Nonword Repetition).
      RESULTS: A differentiation of each clinical group with a multivariate statistical
      tool (discriminant analysis) functioned successfully. Children with APD were
      significantly distinguished from unimpaired children with an accuracy of 94.8 %
      (cross-validated in 92.2 %) via four test variables: (1) Auditory Sequential
      Memory of digits; (2) Phoneme Discrimination; (3) Nonword Repetition; (4) Word
      Understanding in Background Noise. CONCLUSIONS: The quality of the diagnostic a
      priori-grouping using a multivariate statistics (discriminant analysis) could be
      confirmed for first graders too.

PMID- 29448289
TI  - Lessons from pathological analysis of recurrent early esophageal squamous cell
      neoplasia after complete endoscopic radiofrequency ablation.
AB  - BACKGROUND:  Endoscopic radiofrequency ablation (RFA) is a treatment option for
      early esophageal squamous cell neoplasia (ESCN); however, long-term follow-up
      studies are lacking. The risks of local recurrence and "buried cancer" are also
      uncertain. METHODS:  Patients with flat-type ESCN who were treated with balloon
      type +/- focal-type RFA were consecutively enrolled. Follow-up endoscopy was
      performed at 1, 3, and 6 months, and then every 6 months thereafter. Endoscopic
      resection was performed for persistent and recurrent ESCN, and the histopathology
      of resected specimens was assessed. RESULTS:  A total of 35 patients were treated
      with RFA, of whom 30 (86 %) achieved a complete response, three were lost to
      follow-up, and five (14 %) developed post-RFA stenosis. Two patients had
      persistent ESCN and received further endoscopic resection, in which the resected
      specimens all revealed superficial submucosal invasive cancer. Six of the 30
      patients with successful RFA (20 %) developed a total of seven episodes of local
      recurrence (mean size 1.4 cm) during the follow-up period (mean 40.1 months), all
      of which were successfully resected endoscopically without adverse events.
      Histological analysis of the resected specimens revealed that six (86 %) had
      esophageal glandular ductal involvement, all of which extended deeper than the
      muscularis mucosae layer. Immunohistochemistry staining for P53 and Ki67
      suggested a clonal relationship between the ductal involvement and epithelial
      cells. None of the tumors extended out of the ductal structure; no cases of
      cancer buried beneath the normal neosquamous epithelium were found. CONCLUSIONS: 
      Because ductal involvement is not uncommon and may be related to recurrence, the
      use of RFA should be conservative and may not be the preferred primary treatment
      for early ESCN.

PMID- 29448290
TI  - Characterization of Severe Arterial Phase Respiratory Motion Artifact on
      Gadoxetate Disodium-Enhanced MRI - Assessment of Interrater Agreement and
      Reliability.
AB  - PURPOSE:  To assess the interrater agreement and reliability of experienced
      abdominal radiologists in the characterization and grading of arterial phase
      gadoxetate disodium-related respiratory motion artifact on liver MRI. MATERIALS
      AND METHODS:  This prospective multicenter study was initiated by the working
      group for abdominal imaging within the German Roentgen Society (DRG), and
      approved by the local IRB of each participating center. 11 board-certified
      radiologists independently reviewed 40 gadoxetate disodium-enhanced liver MRI
      datasets. Motion artifacts in the arterial phase were assessed on a 5-point
      scale. Interrater agreement and reliability were calculated using the intraclass
      correlation coefficient (ICC) and Kendall coefficient of concordance (W), with p
      < 0.05 deemed significant. RESULTS:  The ICC for interrater agreement and
      reliability were 0.983 (CI 0.973 - 0.990) and 0.985 (CI 0.978 - 0.991),
      respectively (both p < 0.0001), indicating excellent agreement and reliability.
      Kendall's W for interrater agreement was 0.865. A severe motion artifact, defined
      as a mean motion score >= 4 in the arterial phase was observed in 12 patients. In
      these specific cases, a motion score >= 4 was assigned by all readers in 75 % (n
      = 9/12 cases). CONCLUSION:  Differentiation and grading of arterial phase
      respiratory motion artifact is possible with a high level of inter-/intrarater
      agreement and interrater reliability, which is crucial for assessing the
      incidence of this phenomenon in larger multicenter studies. KEY POINTS:   . Inter
      and intrarater agreement for motion artifact scoring is excellent among
      experienced readers.. . Interrater reliability for motion artifact scoring is
      excellent among experienced readers.. . Characterization of severe motion
      artifacts proved feasible in this multicenter study.. CITATION FORMAT: . Ringe
      KI, Luetkens JA, Fimmers R et al. Characterization of Severe Arterial Phase
      Respiratory Motion Artifact on Gadoxetate Disodium-Enhanced MRI - Assessment of
      Interrater Agreement and Reliability. Fortschr Rontgenstr 2017; 190: 341 - 347.

PMID- 29448291
TI  - Subspecialized Radiological Reporting Expedites Turnaround Time of Radiology
      Reports and Increases Productivity.
AB  - INTRODUCTION: To assess the impact of changing from general to subspecialized
      reporting on turnaround time of radiology reports (TAT), the fraction of
      radiology reports available within 24 hours (R< 24 h) and productivity. MATERIALS
      AND METHODS: Reporting workflow in our radiology department was changed from
      general reporting (radiologists report imaging studies of all areas
      [neuroradiological, abdominal, musculoskeletal imaging et cetera]) to
      subspecialized reporting (radiologists solely report imaging studies of their
      subspecialty field [e. g. musculoskeletal]). TAT, R< 24 h and productivity were
      calculated for a 12-month period of general reporting (January-December 2012) and
      compared to a 12-month period of subspecialized reporting (April 2014-March 2015)
      using Mann Whitney U-test, Pearson chi-square test and odds ratios, respectively.
      RESULTS: Report TAT decreased from a median of 17:04 hours (h) during general
      reporting to 3:38 h during subspecialized reporting, resulting in a 4.7-fold
      improvement (p < 0.001). R< 24 h improved significantly from 65 % to 87 % (p <
      0.001). The odds of a radiology report being available < 24 h was 3.6- fold
      higher during subspecialized compared to general reporting. Productivity
      increased from a median of 301 to 376 (reports/full-time radiologist/month) (p =
      0.001). CONCLUSION: Changing the workflow from general to subspecialized
      reporting significantly improved the turnaround time of radiology reports, the
      fraction of radiology reports available within 24 hours and productivity. KEY
      POINTS: . Changing the radiology reporting workflow from general to
      subspecialized reporting is feasible.. . Implementation of subspecialized
      reporting yielded significant improvement of radiology report turnaround time.. .
      Implementation of subspecialized reporting substantially increased the fraction
      of radiology reports available < 24 h.. . Radiologists' productivity increased
      after changing to subspecialized reporting.. CITATION FORMAT: . Stern C, Boehm T,
      Seifert B et al. Subspecialized Radiological Reporting Expedites Turnaround Time
      of Radiology Reports and Increases Productivity. Fortschr Rontgenstr 2018; 190:
      623 - 629.

PMID- 29448293
TI  - ?

PMID- 29448292
TI  - A Trunk Stabilization Exercise Warm-up May Reduce Ankle Injuries in Junior Soccer
      Players.
AB  - The aim of this study was to investigate the efficacy of a trunk stabilization
      exercise warm-up program in reducing the incidence of lower extremity injuries
      among male junior soccer players. Two junior soccer teams participated in this
      study. The intervention (INT) team performed three trunk stabilization exercises
      before practice sessions and games, while a control (CON) team performed their
      usual warm-up without trunk exercises. Both teams engaged in regular soccer
      training and games, and were followed for the incidence of injury. As a result,
      overall injury incidence rates (IRs) were 2.65 injuries/1,000 h and 4.94
      injuries/1,000 h in the INT and CON teams, respectively (incidence rate ratio
      [IRR]=0.54, 95% confidence interval [CI]=0.32-0.89, p=0.013). The IR of acute
      injuries was significantly lower in the INT team (1.91 injuries/1,000 h) than in
      the CON team (4.06 injuries/1,000 h) (IRR=0.47, 95%CI=0.26-0.84, p=0.009).
      Regarding injury sites, the IRs of ankle injuries in the INT team (0.32
      injuries/1,000 h) were significantly lower than that in the CON team (2.28
      injuries/1,000 h) (IRR=0.14, 95%CI=0.04-0.47, p<0.001). These results suggest
      that a warm-up program comprising trunk stabilization exercises alone can prevent
      acute injuries, especially ankle injuries.

PMID- 29448294
TI  - Impact of Multidrug Resistance Protein-4 Inhibitors on Modulating Platelet
      Function and High on-Aspirin Treatment Platelet Reactivity.
AB  - Platelet multidrug resistance protein 4 (MRP4) plays a modulating role on
      platelet activation. Platelet function and thrombus formation are impaired in
      MRP4 knockout mice models, and, among aspirin-treated patients, high on-aspirin
      residual platelet reactivity (HARPR) positively correlates with MRP4 levels. To
      better understand the effects of MRP4 on platelet function, the aim of this
      investigation was to assess the impact of cilostazol-induced inhibition of MRP4
      mediated transport and assess aspirin-induced antiplatelet effects and rates of
      HARPR in human subjects.Cilostazol-dependent inhibition of MRP4-mediated
      transport was assessed with the release of the fluorescent adduct bimane
      glutathione and aspirin entrapment. Effect of Cilostazol on cAMP inhibition was
      evaluated by vasodilator-stimulated phosphoprotein (VASP). Platelet function was
      studied by collagen and TRAP-6-induced platelet aggregation and
      secretion.Cilostazol reduced the release of bimane-glutathione and enhanced
      aspirin entrapment demonstrating an inhibitory effect on MRP4 in platelets. VASP
      phosphorylation was absent until 10 seconds after addition of cilostazol, and
      becomes evident after 30 seconds. An inhibitory effect on platelet aggregation
      and secretion was found in activated platelets, with threshold concentration of
      agonists, 10 seconds after addition of cilostazol, supporting a role of MRP4 on
      platelet function that is cAMP independent. Cilostazol effects were also shown in
      aspirin-treated platelets. A reduction of platelet aggregation and secretion were
      observed in aspirin-treated patients with HARPR.This study supports the role of
      MRP4 on modulating platelet function which occurs through cAMP-independent
      mechanisms. Moreover, inhibition of MRP4 induced by cilostazol enhances aspirin
      induced antiplatelet effects and reduces HARPR.

PMID- 29448295
TI  - Recombinant FXIII (rFXIII-A2) Prophylaxis Prevents Bleeding and Allows for
      Surgery in Patients with Congenital FXIII A-Subunit Deficiency.
AB  - Recombinant factor XIII-A2 (rFXIII-A2) was developed for prophylaxis and
      treatment of bleeds in patients with congenital FXIII A-subunit deficiency.
      mentorTM2 (NCT00978380), a multinational, open-label, single-arm, multiple-dosing
      extension to the pivotal mentorTM1 trial, assessed long-term safety and efficacy
      of rFXIII-A2 prophylaxis in eligible patients (patients with severe [<0.05 IU/mL]
      congenital FXIII subunit A deficiency) aged >=6 years. Patients received 35 IU/kg
      rFXIII-A2 (exact dosing) every 28 +/- 2 days for >=52 weeks. Primary endpoint was
      safety (adverse events including immunogenicity); secondary endpoints were rate
      of bleeds requiring FXIII treatment, haemostatic response after one 35 IU/kg
      rFXIII-A2 dose for breakthrough bleeds and withdrawals due to lack of rFXIII-A2
      efficacy. Steady-state pharmacokinetic variables were also summarized. Elective
      surgery was permitted during the treatment period. Sixty patients were exposed to
      rFXIII-A2; their median age was 26.0 years (range: 7.0-77.0). rFXIII-A2 was well
      tolerated without any safety concerns. No non-neutralizing or neutralizing
      antibodies (inhibitors) against FXIII were detected. Mean annualized bleeding
      rate (ABR) was 0.043/patient-year. Mean spontaneous ABR was 0.011/patient-year.
      No patients withdrew due to lack of efficacy. Geometric mean FXIII trough level
      was 0.17 IU/mL. Geometric terminal half-life was 13.7 days. rFXIII-A2 prophylaxis
      provided sufficient haemostatic coverage for 12 minor surgeries without the need
      for additional FXIII therapy; eight procedures were performed within 7 days of
      the patient's last scheduled rFXIII-A2 dose, and four were performed 10 to 21
      days after the last dose.

PMID- 29448296
TI  - alpha2-Macroglobulin Is a Significant In Vivo Inhibitor of Activated Protein C
      and Low APC:alpha2M Levels Are Associated with Venous Thromboembolism.
AB  - BACKGROUND:  Activated protein C (APC) is a major regulator of thrombin
      formation. Two major plasma inhibitors form complexes with APC, protein C
      inhibitor (PCI) and alpha1-antitrypsin (alpha1AT), and these complexes have been
      quantified by specific enzyme-linked immunosorbent assays (ELISAs). Also,
      complexes of APC with alpha2-macroglobulin (alpha2M) have been observed by
      immunoblotting. Here, we report an ELISA for APC:alpha2M complexes in plasma.
      METHODS:  Plasma samples were pre-treated with dithiothreitol and then with
      iodoacetamide. The detection range of the newly developed APC:alpha2M assay was
      0.031 to 8.0 ng/mL of complexed APC. Following infusions of APC in humans and
      baboons, complexes of APC with alpha2M, PCI and alpha1AT were quantified. These
      complexes as well as circulating APC were also measured in 121 patients with a
      history of venous thromboembolism (VTE) and 119 matched controls. RESULTS:  In
      all the in vivo experiments, alpha2M was a significant APC inhibitor. The VTE
      case-control study showed that VTE patients had significantly lower APC:alpha2M
      and APC levels than the controls (p < 0.001). Individuals in the lowest quartile
      of APC:alpha2M or the lowest quartile of APC had approximately four times more
      VTE risk than those in the highest quartile of APC:alpha2M or of APC. The risk
      increased for individuals with low levels of both parameters. CONCLUSION:  The
      APC:alpha2M assay reported here may be useful to help monitor the in vivo fate of
      APC in plasma. In addition, our results show that a low APC:alpha2M level is
      associated with increased VTE risk.

PMID- 29448298
TI  - Reply to "melanoma pattern of care in ontario: A call for strategic alignment of
      multidisciplinary care)".

PMID- 29448297
TI  - Anticoagulant Preferences and Concerns among Venous Thromboembolism Patients.
AB  - BACKGROUND:  Warfarin and direct oral anticoagulants (DOACs) are used for the
      initial treatment and secondary prevention of venous thromboembolism (VTE), and
      have similar efficacy. Patient concerns and preferences are important
      considerations when selecting an anticoagulant, yet these are not well studied.
      METHODS:  VTE patients (n = 519) were surveyed from online sources
      (clotconnect.org, stoptheclot.org and National Blood Clot Alliance Facebook
      followers [n = 495]) and a haematology clinic in Vermont (n = 24). RESULTS: 
      Patients were 83% females and on average (+/-standard deviation [SD]) 45.7 +/-
      13.1 years; 65% self-reported warfarin as their initial VTE treatment and 35% a
      DOAC. Proportions reporting being extremely concerned about the following
      outcomes were as follows: recurrent VTE 33%, major bleeding 21%, moderate
      bleeding 16% and all-cause death 29%. When asked about oral anticoagulant
      characteristics, patients strongly preferred anticoagulants that are reversible
      (53%), and for which blood drug levels can be monitored (30%). Lower proportions
      agreed with statements that regular blood testing is inconvenient (18%), that
      they are comfortable using the newest drug versus an established drug (15%) and
      that it is difficult to change their diet to accommodate their anticoagulant
      (17%). In multivariable-adjusted models, patients tended to have had as their
      initial treatment, and to currently be taking, the oral anticoagulant option they
      personally preferred. DISCUSSION:  Patients held the greatest concern for
      recurrent VTE and mortality, regardless of which treatment they were prescribed.
      Potential weaknesses of warfarin (e.g., dietary restrictions, regular monitoring)
      were generally not considered onerous, while warfarin's advantages (e.g., ability
      to monitor) were viewed favourably.

PMID- 29448299
TI  - Early and late complications in the reconstructed mandible with free fibula
      flaps.
AB  - BACKGROUND AND OBJECTIVES: Evaluation of mandibular reconstructions with free
      fibula flaps. Identification of factors associated with major recipient site
      complications, that is, necessitating surgical intervention under general
      anaesthesia. METHODS: Seventy-nine reconstructions were included. The following
      factors were analyzed: fixation type, number of osteotomies, site of defect
      (bilateral/unilateral), surgeon, sex, ASA classification, continuous smoking,
      pathological N-stage, age, defect size, flap ischemic time, and postoperative
      radiotherapy. Proportional hazards regression was used to test the effect on the
      time between reconstruction and intervention. RESULTS: Sixty-nine (87%) of the 79
      fibula flaps were successful at the last follow-up. Forty-eight major recipient
      site complications occurred in 41 reconstructions. Nineteen complications
      required surgical intervention within six weeks and were mostly vascular
      problems, necessitating immediate intervention. These early complications were
      associated with defects crossing the midline, with an estimated relative risk of
      5.3 (CI 1.1-20, P = 0.01). Twenty-nine complications required surgical
      intervention more than 6 weeks after the reconstruction. These late complications
      generally occurred after months or years, and were associated with smoking, with
      an estimated relative risk of 2.8 (CI 1.0-8.3, P = 0.05). CONCLUSIONS: Fibula
      flaps crossing the midline have a higher risk of early major recipient site
      complications than unilateral reconstructions. Smoking increases the risk of late
      complications.

PMID- 29448300
TI  - Identification of preoperative factors associated with outcomes following
      surgical management of intra-abdominal recurrent or metastatic GIST following
      neoadjuvant tyrosine kinase inhibitor therapy.
AB  - BACKGROUND: The role of surgical resection in the treatment of patients with
      metastatic/recurrent gastrointestinal stromal tumors (GIST) is unclear. The aim
      of this study was to identify preoperative factors associated with oncologic
      outcomes for recurrent/metastatic GIST after tyrosine kinase inhibitor (TKI)
      therapy. METHODS: We identified 107 patients with metastatic or recurrent GIST
      treated with TKIs and surgical resection (2002-2012). Patients that underwent
      palliative or incomplete resection were excluded. Complete resection was achieved
      in 87 patients which comprise the analytic cohort. Univariate and multivariate
      analyses were conducted to identify risk factors for GIST-specific survival (DSS)
      and time-to-recurrence (TTR). RESULTS: At a median follow-up of 51 months (91
      months for survivors), median DSS was 74 months and TTR was 21 months. By
      univariate analysis, unifocal disease, duration of TKI < 365 days, and no
      evidence of radiographic progression were associated with improved TTR and DSS.
      Multivariate Cox regression demonstrated that evidence of radiographic
      progression was associated with shorter DSS (HR 2.53, 95%CI = 1.27-5.06, P =
      0.008) and increased risk of recurrence (HR 3.33, 95%CI = 1.91-5.82, P < 0.001).
      CONCLUSIONS: Patients with unifocal disease and radiographic evidence of response
      to TKI therapy may achieve improved oncologic outcomes when complete surgical
      resection is achieved following treatment with TKI.

PMID- 29448301
TI  - Histological expression of methionine adenosyl transferase (MAT) 2A as a post
      surgical prognostic surrogate in patients with hepatocellular carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Deregulation of methionine adenosyltransferase (MAT)
      is involved in hepatocarcinogenesis. This study aimed to investigate the
      prognostic implications of the level of histological MAT1A and MAT2A in patients
      with resected hepatocellular carcinoma (HCC). METHODS: A total of 210 patients
      with HCC who underwent curative resection between 2004 and 2011 were included.
      The levels of MAT proteins were immunohistochemically measured. RESULTS: MAT1A
      and MAT2A were over-expressed in 134 (63.8%) and 124 (59.1%) of the 210 tumor
      tissues, respectively. Up-regulation of tumoral MAT1A was independently
      associated with male gender, and inversely related to tumors >5 cm (adjusted odds
      ratios [OR] 2.59, P = 0.008, and OR 0.44, P = 0.012, respectively). Enhanced
      MAT2A expression was significantly related to age >=60 years and serum AFP >200
      ng/mL (OR 0.51, P = 0.030; and OR 2.65, P = 0.003; respectively). Tumoral MAT2A
      over-expression independently predicted an increased rate of recurrence within 1
      year after hepatectomy (adjusted hazard ratio [HR] 2.45, P = 0.012), but that was
      not the case for MAT1A expression (HR 0.90, P = 0.744). High MAT2A was also an
      independent predictor of early recurrence (HR 2.54, P = 0.034) in the subset of
      patients without microvascular invasion (n = 155). CONCLUSIONS: Over-expression
      of MAT2A in HCC may be a useful biomarker for predicting and monitoring tumor
      recurrence, especially early after hepatic resection.

PMID- 29448302
TI  - Retroperitoneal laparoscopic adrenalectomy with transient renal artery occlusion
      for large adrenal tumors (>=8 cm).
AB  - OBJECTIVES: To analyze our experience in retroperitoneal laparoscopic
      adrenalectomy (RLA) with transient renal artery occlusion for large adrenal
      tumors (>=8 cm) and to explore the safety and feasibility of this surgical
      procedure. METHODS: A retrospective cohort study was conducted with a surgical
      data review of 18 patients with large adrenal tumors who underwent RLA with
      transient renal artery occlusion in our hospital. RESULTS: Eighteen patients were
      treated by RLA with transient occlusion of the renal artery, and none were
      converted to open adrenalectomy. The renal artery occlusion time, operative time,
      estimated blood loss, perirenal drainage time, postoperative hospital stay, and
      postoperative drainage were 7.6 +/- 1.0 min, 176.3 +/- 49.7 min, 247.2 +/- 274.1
      mL, 4.1 +/- 1.02 days, 6.3 +/- 1.4 days, and 73.6 +/- 47.9 mL, respectively. No
      severe complications occurred, with the exception of hemodynamic instability in
      one patient with a pheochromocytoma and one transfusion during the operation.
      Only one case of adrenal crisis occurred postoperatively. Pathological
      examination revealed 9 cases of pheochromocytoma, 6 cases of adrenal myelolipoma,
      1 case of adrenal ganglioneuroma, 1 case of hygromata, and 1 case of adrenal
      teratoma. No recurrence or evidence of metastasis was observed during the 7-to-30
      month follow-up period. CONCLUSION: RLA with transient renal artery occlusion is
      a feasible, effective, and safe treatment for large adrenal tumors (>=8 cm).

PMID- 29448304
TI  - Neutrophil: Lymphocyte ratio as a method of predicting complications following
      hepatic resection for colorectal liver metastasis.
AB  - BACKGROUND AND OBJECTIVES: Approximately 30-50% of patients with colorectal
      cancer develop liver metastasis for which liver resection is the only hope for
      potential cure. However, hepatic resection is associated with considerable
      morbidity. The aim was to detect early complications by utilising the neutrophil:
      lymphocyte ratio (NLR). METHODS: We performed a retrospective cohort study of
      patients undergoing hepatic resection at a single institution between 2008 and
      2016. Baseline demographics and complications within 30 days following surgery
      were recorded, with blood tests measured until day 7. Statistical analysis was
      performed using Mann Whitney and ROC analysis. RESULTS: One hundred eighty-eight
      operations were included. 47.3% had an associated complication, of which 31.46%
      were major. The median NLR was 6.31 across the cohort, 5.44 for uncomplicated
      procedures, 7.0 for complications and 10.65 in major complications. Median NLR
      was the best parameter for detecting major complications versus minor
      complications (AUC 0.74) as opposed to lymphocytes (AUC 0.65), neutrophils (AUC
      0.60), and CRP (AUC 0.60). The diagnostic ability of NLR increased further when
      predicting major complications versus an uncomplicated recovery (AUC 0.78), and
      it was the only significant parameter in the early post-operative period on days
      2, 3, and 4 (AUC 0.70, 0.72, and 0.75). CONCLUSIONS: The NLR may have a role in
      predicting complications following hepatic resection for CLM, and with earlier
      detection, potentially improving outcomes.

PMID- 29448305
TI  - Development and validation of a gas chromatography/tandem mass spectrometry
      method for simultaneous quantitation of several antipsychotics in human plasma
      and oral fluid.
AB  - RATIONALE: Antipsychotic drugs are prescription medications used to treat
      psychotic disorders, such as schizophrenia, schizoaffective disorder, or
      psychotic depression. With several antipsychotic drugs currently available all
      over the world, this class of drugs has quickly gained importance in both the
      clinical and forensic context. This work describes the development and validation
      of a methodology for the determination of seven antipsychotic drugs in plasma and
      oral fluid samples. METHODS: The antipsychotic drugs (chlorpromazine, clozapine,
      haloperidol, olanzapine, quetiapine, cyamemazine and, levomepromazine) were
      isolated from 0.2 mL of oral fluid and 0.5 mL of plasma using solid-phase
      extraction (SPE) following analysis by gas chromatography/tandem mass
      spectrometry (GC/MS/MS). The method was validated according to the international
      guidelines in terms of selectivity, linearity, accuracy, precision and recovery.
      RESULTS: The procedure was linear within 2-600 ng/mL (plasma) and 2-400 ng/mL
      (oral fluid), the intervals varying according to the compound; a mean R2 value of
      0.99 was obtained and the calibrator's accuracy (mean relative error) was within
      a +/-15 % interval for all concentrations. The limits of detection ranged from 1
      to 10 ng/mL. Within- and between-run precision and accuracy were acceptable for
      all studied compounds. The extraction efficiency of the process ranged from 79%
      to 95%. The method was applied to authentic specimens. CONCLUSIONS: The described
      method was proven selective and sensitive for the determination of antipsychotics
      in low sample volumes using SPE and GC/MS/MS. This method was considered suitable
      not only for routine analysis of patients undergoing antipsychotic treatment (to
      evaluate compliance), but also in forensic scenarios where the studied compounds
      may be involved. To the best of our knowledge, this is the first work that
      reports the determination of antipsychotic drugs in oral fluid using MS/MS.

PMID- 29448303
TI  - Nomogram predicting the risk of recurrence after curative-intent resection of
      primary non-metastatic gastrointestinal neuroendocrine tumors: An analysis of the
      U.S. Neuroendocrine Tumor Study Group.
AB  - BACKGROUND: The risk of recurrence after resection of non-metastatic gastro
      entero-pancreatic neuroendocrine tumors (GEP-NET) is poorly defined. We
      developed/validated a nomogram to predict risk of recurrence after curative
      intent resection. METHODS: A training set to develop the nomogram and test set
      for validation were identified. The predictive ability of the nomogram was
      assessed using c-indices. RESULTS: Among 1477 patients, 673 (46%) were included
      in the training set and 804 (54%) in y the test set. On multivariable analysis,
      Ki-67, tumor size, nodal status, and invasion of adjacent organs were independent
      predictors of DFS. The risk of death increased by 8% for each percentage increase
      in the Ki-67 index (HR 1.08, 95% CI, 1.05-1.10; P < 0.001). GEP-NET invading
      adjacent organs had a HR of 1.65 (95% CI, 1.03-2.65; P = 0.038), similar to
      tumors >=3 cm (HR 1.67, 95% CI, 1.11-2.51; P = 0.014). Patients with 1-3 positive
      nodes and patients with >3 positive nodes had a HR of 1.81 (95% CI, 1.12-2.87; P
      = 0.014) and 2.51 (95% CI, 1.50-4.24; P < 0.001), respectively. The nomogram
      demonstrated good ability to predict risk of recurrence (c-index: training set,
      0.739; test set, 0.718). CONCLUSION: The nomogram was able to predict the risk of
      recurrence and can be easily applied in the clinical setting.

PMID- 29448306
TI  - ALBI versus Child-Pugh grading systems for liver function in patients with
      hepatocellular carcinoma.
AB  - BACKGROUND: The prognostic performance of the albumin-bilirubin (ALBI) grade in
      hepatocellular carcinoma (HCC) as an objective method of assessing liver function
      was investigated. METHODS: Data from 2099 patients with HCC in Korea were
      collected and analyzed retrospectively. The discriminative performance of ALBI
      grade was compared with Child-Pugh (C-P) grade for different stages or
      treatments. RESULTS: The median follow up duration was 16.2 months (range: 1.0
      124.9). The median survival times were 49.7 months for C-P grade A (65.8%), 12.4
      months for C-P grade B (25.5%), and 4.2 months for C-P grade C (8.6%) (P <
      0.001). The median survival times were 84.2 months for ALBI grade 1 (32.8%), 25.5
      months for ALBI grade 2 (53.5%), and 7.7 months for ALBI grade 3 (13.7%) (P <
      0.001). In early UICC stages, ALBI grade showed better discriminative performance
      than C-P grade. In curative treatments, ALBI grade also showed better
      discriminative performance than C-P grade (Harrell's C: 0.624 (C-P grade) vs
      0.667 [ALBI grade]). CONCLUSIONS: ALBI grade provided better prognostic
      performance in survival analysis and better distribution of the grades than C-P
      grade in HCC, suggesting that ALBI grade could be a good alternative grading
      system for liver function in patients with HCC.

PMID- 29448307
TI  - Histopathological changes resulting from selective internal radiotherapy (SIRT).
AB  - BACKGROUND: Selective internal radiotherapy (SIRT) has emerged as an effective
      therapy for patients with liver malignancies. Here, we report our analysis of
      histopathological changes in tumors and healthy liver tissue after SIRT and liver
      resection. Our main intent was to determine if specific histopathological changes
      occur in tumor and normal liver tissues. METHODS: We identified 17 patients in
      whom SIRT was applied to achieve liver resectability. Samples were taken from the
      resected liver tissue. The tumor, tumor peripheries, and tumor-free tissue were
      examined microscopically. RESULTS: Microspheres were identified in the vascular
      tumor bed, tumor-free liver, and portal tract. More microspheres were detected in
      the tumor than in the healthy liver tissue. When the effects of SIRT were
      analyzed, most patients showed a partial pathological response. Specific
      histopathological changes could not be described. We did not find any typical
      signs of radiation-induced hepatitis in healthy liver tissue. CONCLUSIONS: Our
      findings support the clinical experience of effective tumor control after SIRT
      together with minimal impairment of healthy liver tissue. The observed
      histopathological changes suggest that SIRT might play a role in preoperative
      downsizing of liver malignancies.

PMID- 29448308
TI  - Perioperative outcomes and survival following neoadjuvant stereotactic body
      radiation therapy (SBRT) versus intensity-modulated radiation therapy (IMRT) in
      pancreatic adenocarcinoma.
AB  - BACKGROUND AND OBJECTIVES: To compare outcomes in patients receiving neoadjuvant
      stereotactic body radiation therapy (SBRT) with those receiving intensity
      modulated radiation therapy (IMRT) for pancreatic adenocarcinoma. METHODS: We
      analyzed patients receiving neoadjuvant SBRT for borderline resectable (BRPC) and
      locally advanced pancreatic cancer (LAPC) (2012-2016). Differences in baseline
      characteristics, perioperative outcomes, progression-free survival (PFS), and
      overall survival (OS) were compared. RESULTS: Seventy-five (82.4%) patients
      received SBRT and 16 (17.6%) received IMRT. There were no differences in surgical
      resection rates in the SBRT (n = 38, 50.7%) and IMRT (n = 11, 68.8%) groups (P =
      0.188). Among resected patients, there was no difference in postoperative
      outcomes or pathologic outcomes including lymph node status, margin status,
      lymphovascular and perineural invasion, or pathologic response to neoadjuvant
      treatment (P > 0.05). Among all patients, median PFS and OS were 9.9 and 23.5
      months in the SBRT group, respectively, and 15.3 and 21.8 months in the IMRT
      group, respectively (P > 0.05). Similarly, there was no difference in PFS or OS
      between groups when stratified by BRPC, LAPC, and surgically resected patients (P
      > 0.05). CONCLUSIONS: In the neoadjuvant setting, SBRT and IMRT appear to have
      similar rates of resection, perioperative outcomes, and survival outcomes, but
      additional studies with increased sample size and longer follow up are needed.

PMID- 29448309
TI  - The value of additional bevacizumab in patients with high-risk stroma-high colon
      cancer. A study within the QUASAR2 trial, an open-label randomized phase 3 trial.
AB  - INTRODUCTION: Patients with a high stroma percentage within the primary tumor
      have a poor prognosis. In this study, we investigate whether anti-angiogenic
      therapy might improve survival of patients with a stroma-high profile with
      potentially increased angiogenesis. MATERIALS AND METHODS: Tissue samples of the
      primary tumor of 965 colon cancer patients participating in the QUASAR2 trial
      were analyzed for tumor-stroma ratio (TSR). Stroma-high (>50%) and stroma-low
      (<=50%) groups were evaluated with respect to survival. RESULTS: Disease free
      survival (DFS) was significantly lower in the stroma-high group (HR 1.53, 95%CI
      1.19-1.95, P = 0.001). No difference in DFS was seen with respect to treatment
      with capecitabine alone (CAP) or capecitabine with bevacizumab (CAPBEV) (Stroma
      high HR 1.00, 95%CI 0.69-1.46, P = 0.996; stroma-low HR 1.02, 95%CI 0.75-1.41, P
      = 0.883). A significant difference in survival was seen comparing groups with or
      without vascular invasion (DFS P < 0.001). A correlation between vascular
      invasion and stroma-high was seen (chi2 -test P = 0.043). DISCUSSION AND
      CONCLUSIONS: The TSR confirmed to be a strong prognosticator for disease-free
      survival in a selected high-risk patient population. No benefit was found in
      response to treatment with bevacizumab when stratified for TSR. TSR showed to
      have an additional prognostic value in patients with vascular invasion present in
      the primary tumor.

PMID- 29448310
TI  - Liquid chromatography/mass spectrometry-based plasma metabolic profiling study of
      escitalopram in subjects with major depressive disorder.
AB  - Liquid chromatography-mass spectrometry (LC-MS) method revealed the plasma
      metabolite profiles in major depressive disorder patients treated with
      escitalopram (ECTP) (n = 7). Depression severity was assessed according to the 17
      item Hamilton Depression Rating Scale. Metabolic profiles were derived from major
      depressive disorder subject blood samples collected after ECTP treatment. Blood
      plasma was separated and processed in order to effectively extract metabolites,
      which were then analyzed using LC-MS. We identified 19 metabolites and elucidated
      their structures using LC-tandem MS (LC-MS/MS) combined with elemental
      compositions derived from accurate mass measurements. We further used online H/D
      exchange experiments to verify the structural elucidations of each metabolite.
      Identifying molecular metabolites may provide critical insights into the
      pharmacological and clinical effects of ECTP treatment and may also provide
      useful information informing the development of new antidepressant treatments.
      These detailed plasma metabolite analyses may also be used to identify optimal
      dose concentrations in psychopharmacotherapeutic treatment through drug
      monitoring, as well as forming the basis for response predictions in depressed
      subjects.

PMID- 29448311
TI  - Enhancing decision-making about adjuvant chemotherapy in early breast cancer
      following EndoPredict testing.
AB  - OBJECTIVE: Chemotherapy side-effects can be substantial. There is increasing
      recognition that some oestrogen receptor positive (ER +ve), human epidermal
      growth factor receptor 2 negative (HER2 -ve) patients with breast cancer derive
      no benefit from chemotherapy and experience only iatrogenic harm. Gene expression
      profiling tests help refine recurrence risk and likely chemotherapy benefit.
      EndoPredict(r) is one such test, which classifies risks of distant recurrence as
      low or high in patients treated with surgery and adjuvant endocrine therapy
      alone. We compared treatment decisions pre-test and post-test results, patients'
      anxiety, decisional conflict, and oncologists' confidence about the decisions
      made. METHODS: Fourteen oncologists in 7 UK hospitals saw 149 pts judged to have
      equivocal indications for chemotherapy. Provisional treatment decisions were
      recorded then reconsidered when EPClin results were available. Pre-test and post
      test results, patients completed State/Trait Anxiety Inventories (STAI), and the
      decisional conflict scale. Oncologists also recorded basic clinical details,
      their agreement with, and confidence about treatment decisions. RESULTS: Sixty
      seven percent patients initially prescribed endocrine alone with high risk result
      upgraded to endocrine+chemotherapy (E + C); 83% prescribed E + C and had low risk
      scores, downgraded to E. None of 46 patients initially favouring E alone, who
      were low risk, changed decisions. Oncologists' confidence about decisions was
      significantly increased following the results (P = 0.002). Patients with
      downgraded treatment decisions had significantly lower anxiety scores (P =
      0.045); those upgraded had increased scores (P = 0.001). Overall decisional
      conflict and uncertainty fell significantly post-test (P < 0.022). CONCLUSIONS:
      EndoPredict scores increased oncologists' and patients' decision-making
      confidence, generally improving the matching of risk with therapy decisions.

PMID- 29448312
TI  - Prognostic significance of poorly differentiated clusters and tumor budding in
      colorectal liver metastases.
AB  - BACKGROUND: Histomorphological features have been described as prognostic factors
      after resection of colorectal liver metastases (CLM). The objectives of this
      study were to assess the prognostic significance of tumor budding (TB) and poorly
      differentiated clusters (PDC) among CLM, and their association with other
      prognostic factors. METHODS: We evaluated 229 patients who underwent a first
      resection of CLM. Slides stained by HE were assessed for TB, PDC, tumor border
      pattern, peritumoral pseudocapsule, peritumoral, and intratumoral inflammatory
      infiltrate. Lymphatic and portal invasion were evaluated through D2-40 and CD34
      antibody. RESULTS: Factors independently associated with poor overall survival
      were nodules>4 (P = 0.002), presence of PDC G3 (P = 0.007), portal invasion (P =
      0.005), and absence of tumor pseudocapsule (P = 0.006). Factors independently
      associated with disease-free survival included number of nodules>4 (P < 0.001),
      presence of PDC G3 (P = 0.005), infiltrative border (P = 0.031), portal invasion
      (P = 0.006), and absent/mild peritumoral inflammatory infiltrate (P = 0.002). PDC
      and TB were also associated with histological factors, as portal invasion (TB),
      peritumoral inflammatory infiltration (PDC), infiltrative border, and absence of
      tumor pseudocapsule (TB and PDC). CONCLUSIONS: This is the first study
      demonstrating PDC as a prognostic factor in CLM. TB was also a prognostic factor,
      but it was not an independent predictor of survival.

PMID- 29448314
TI  - Optimal nonlinear filtering using the finite-volume method.
AB  - Optimal sequential inference, or filtering, for the state of a deterministic
      dynamical system requires simulation of the Frobenius-Perron operator, that can
      be formulated as the solution of a continuity equation. For low-dimensional,
      smooth systems, the finite-volume numerical method provides a solution that
      conserves probability and gives estimates that converge to the optimal continuous
      time values, while a Courant-Friedrichs-Lewy-type condition assures that
      intermediate discretized solutions remain positive density functions. This method
      is demonstrated in an example of nonlinear filtering for the state of a simple
      pendulum, with comparison to results using the unscented Kalman filter, and for a
      case where rank-deficient observations lead to multimodal probability
      distributions.

PMID- 29448313
TI  - Causes of plasma column contraction in surface-wave-driven discharges in argon at
      atmospheric pressure.
AB  - In this work we compute the main features of a surface-wave-driven plasma in
      argon at atmospheric pressure in view of a better understanding of the
      contraction phenomenon. We include the detailed chemical kinetics dynamics of Ar
      and solve the mass conservation equations of the relevant neutral excited and
      charged species. The gas temperature radial profile is calculated by means of the
      thermal diffusion equation. The electric field radial profile is calculated
      directly from the numerical solution of the Maxwell equations assuming the
      surface wave to be propagating in the TM_{00} mode. The problem is considered to
      be radially symmetrical, the axial variations are neglected, and the equations
      are solved in a self-consistent fashion. We probe the model results considering
      three scenarios: (i) the electron energy distribution function (EEDF) is
      calculated by means of the Boltzmann equation; (ii) the EEDF is considered to be
      Maxwellian; (iii) the dissociative recombination is excluded from the chemical
      kinetics dynamics, but the nonequilibrium EEDF is preserved. From this analysis,
      the dissociative recombination is shown to be the leading mechanism in the
      constriction of surface-wave plasmas. The results are compared with mass
      spectrometry measurements of the radial density profile of the ions Ar^{+} and
      Ar_{2}^{+}. An explanation is proposed for the trends seen by Thomson scattering
      diagnostics that shows a substantial increase of electron temperature towards the
      plasma borders where the electron density is small.

PMID- 29448315
TI  - Lumping of degree-based mean-field and pair-approximation equations for
      multistate contact processes.
AB  - Contact processes form a large and highly interesting class of dynamic processes
      on networks, including epidemic and information-spreading networks. While
      devising stochastic models of such processes is relatively easy, analyzing them
      is very challenging from a computational point of view, particularly for large
      networks appearing in real applications. One strategy to reduce the complexity of
      their analysis is to rely on approximations, often in terms of a set of
      differential equations capturing the evolution of a random node, distinguishing
      nodes with different topological contexts (i.e., different degrees of different
      neighborhoods), such as degree-based mean-field (DBMF), approximate-master
      equation (AME), or pair-approximation (PA) approaches. The number of differential
      equations so obtained is typically proportional to the maximum degree k_{max} of
      the network, which is much smaller than the size of the master equation of the
      underlying stochastic model, yet numerically solving these equations can still be
      problematic for large k_{max}. In this paper, we consider AME and PA, extended to
      cope with multiple local states, and we provide an aggregation procedure that
      clusters together nodes having similar degrees, treating those in the same
      cluster as indistinguishable, thus reducing the number of equations while
      preserving an accurate description of global observables of interest. We also
      provide an automatic way to build such equations and to identify a small number
      of degree clusters that give accurate results. The method is tested on several
      case studies, where it shows a high level of compression and a reduction of
      computational time of several orders of magnitude for large networks, with
      minimal loss in accuracy.

PMID- 29448316
TI  - Synchronized oscillations and acoustic fluidization in confined granular
      materials.
AB  - According to the acoustic fluidization hypothesis, elastic waves at a
      characteristic frequency form inside seismic faults even in the absence of an
      external perturbation. These waves are able to generate a normal stress which
      contrasts the confining pressure and promotes failure. Here, we study the
      mechanisms responsible for this wave activation via numerical simulations of a
      granular fault model. We observe the particles belonging to the percolating
      backbone, which sustains the stress, to perform synchronized oscillations over
      ellipticlike trajectories in the fault plane. These oscillations occur at the
      characteristic frequency of acoustic fluidization. As the applied shear stress
      increases, these oscillations become perpendicular to the fault plane just before
      the system fails, opposing the confining pressure, consistently with the acoustic
      fluidization scenario. The same change of orientation can be induced by external
      perturbations at the acoustic fluidization frequency.

PMID- 29448317
TI  - Magnetic flux conservation in an imploding plasma.
AB  - The theory of magnetic flux conservation is developed for a subsonic plasma
      implosion and used to describe the magnetic flux degradation in the MagLIF
      concept [S. A. Slutz et al., Phys. Plasmas 17, 056303 (2010)10.1063/1.3333505].
      Depending on the initial magnetic Lewis and Peclet numbers and the electron Hall
      parameter, the implosion falls into either a superdiffusive regime in which the
      magnetization decreases or a magnetized regime in which the magnetization
      increases. Scaling laws for magnetic field, temperature, and magnetic flux losses
      in the hot spot of radius R are obtained for both regimes. The Nernst velocity
      convects the magnetic field outwards, pushing it against the liner and enhancing
      the magnetic field diffusion, thereby reducing the magnetic field compression and
      degrading the implosion performance. However, in the magnetized regime, the core
      of the hot spot becomes magnetically insulated and undergoes an ideal adiabatic
      compression (T~R^{-4/3} compared to T~R^{-2/3} without magnetic field), while the
      detrimental Nernst term is confined to the outer part of the hot spot. Its effect
      is drastically reduced, improving the magnetic flux conservation.

PMID- 29448318
TI  - Original electric-vertex formulation of the symmetric eight-vertex model on the
      square lattice is fully nonuniversal.
AB  - The partition function of the symmetric (zero electric field) eight-vertex model
      on a square lattice can be formulated either in the original "electric" vertex
      format or in an equivalent "magnetic" Ising-spin format. In this paper, both
      electric and magnetic versions of the model are studied numerically by using the
      corner transfer matrix renormalization-group method which provides reliable data.
      The emphasis is put on the calculation of four specific critical exponents,
      related by two scaling relations, and of the central charge. The numerical method
      is first tested in the magnetic format, the obtained dependencies of critical
      exponents on the model's parameters agree with Baxter's exact solution, and weak
      universality is confirmed within the accuracy of the method due to the finite
      size of the system. In particular, the critical exponents eta and delta are
      constant as required by weak universality. On the other hand, in the electric
      format, analytic formulas based on the scaling relations are derived for the
      critical exponents eta_{e} and delta_{e} which agree with our numerical data.
      These exponents depend on the model's parameters which is evidence for the full
      nonuniversality of the symmetric eight-vertex model in the original electric
      formulation.

PMID- 29448319
TI  - Crossover from three-dimensional to two-dimensional systems in the nonequilibrium
      zero-temperature random-field Ising model.
AB  - We present extensive numerical studies of the crossover from three-dimensional to
      two-dimensional systems in the nonequilibrium zero-temperature random-field Ising
      model with metastable dynamics. Bivariate finite-size scaling hypotheses are
      presented for systems with sizes L*L*l which explain the size-driven critical
      crossover from two dimensions (l=const, L->infinity) to three dimensions (l?L
      >infinity). A model of effective critical disorder R_{c}^{eff}(l,L) with a unique
      fitting parameter and no free parameters in the R_{c}^{eff}(l,L->infinity) limit
      is proposed, together with expressions for the scaling of avalanche distributions
      bringing important implications for related experimental data analysis,
      especially in the case of thin three-dimensional systems.

PMID- 29448320
TI  - Characterization of microscopic deformation through two-point spatial correlation
      functions.
AB  - The molecular rearrangements of most fluids under flow and deformation do not
      directly follow the macroscopic strain field. In this work, we describe a
      phenomenological method for characterizing such nonaffine deformation via the
      anisotropic pair distribution function (PDF). We demonstrate how the microscopic
      strain can be calculated in both simple shear and uniaxial extension, by
      perturbation expansion of anisotropic PDF in terms of real spherical harmonics.
      Our results, given in the real as well as the reciprocal space, can be applied in
      spectrum analysis of small-angle scattering experiments and nonequilibrium
      molecular dynamics simulations of soft matter under flow.

PMID- 29448321
TI  - Dynamic instability in the hook-flagellum system that triggers bacterial flicks.
AB  - Dynamical bending, buckling, and polymorphic transformations of the flagellum are
      known to affect bacterial motility, but run-reverse-flick motility of
      monotrichous bacteria also involves the even more flexible hook connecting the
      flagellum to its rotary motor. Although flick initiation has been hypothesized to
      involve either static Euler buckling or dynamic bending of the hook, the precise
      mechanism of flick initiation remains unknown. Here, we find that flicks initiate
      via a dynamic instability requiring flexibility in both the hook and flagellum.
      We obtain accurate estimates of forces and torques on the hook that suggest that
      flicks occur for stresses below the (static) Euler buckling criterion, then
      provide a mechanistic model for flick initiation that requires combined bending
      of the hook and flagellum. We calculate the triggering torque-stiffness ratio and
      find that our predicted onset of dynamic instability corresponds well with
      experimental observations.

PMID- 29448322
TI  - Normal modes of weak colloidal gels.
AB  - The normal modes and relaxation rates of weak colloidal gels are investigated in
      calculations using different models of the hydrodynamic interactions between
      suspended particles. The relaxation spectrum is computed for freely draining,
      Rotne-Prager-Yamakawa, and accelerated Stokesian dynamics approximations of the
      hydrodynamic mobility in a normal mode analysis of a harmonic network
      representing several colloidal gels. We find that the density of states and
      spatial structure of the normal modes are fundamentally altered by long-ranged
      hydrodynamic coupling among the particles. Short-ranged coupling due to
      hydrodynamic lubrication affects only the relaxation rates of short-wavelength
      modes. Hydrodynamic models accounting for long-ranged coupling exhibit a
      microscopic relaxation rate for each normal mode, lambda that scales as l^{-2},
      where l is the spatial correlation length of the normal mode. For the freely
      draining approximation, which neglects long-ranged coupling, the microscopic
      relaxation rate scales as l^{-gamma}, where gamma varies between three and two
      with increasing particle volume fraction. A simple phenomenological model of the
      internal elastic response to normal mode fluctuations is developed, which shows
      that long-ranged hydrodynamic interactions play a central role in the
      viscoelasticity of the gel network. Dynamic simulations of hard spheres that gel
      in response to short-ranged depletion attractions are used to test the
      applicability of the density of states predictions. For particle concentrations
      up to 30% by volume, the power law decay of the relaxation modulus in simulations
      accounting for long-ranged hydrodynamic interactions agrees with predictions
      generated by the density of states of the corresponding harmonic networks as well
      as experimental measurements. For higher volume fractions, excluded volume
      interactions dominate the stress response, and the prediction from the harmonic
      network density of states fails. Analogous to the Zimm model in polymer physics,
      our results indicate that long-ranged hydrodynamic interactions play a crucial
      role in determining the microscopic dynamics and macroscopic properties of weak
      colloidal gels.

PMID- 29448323
TI  - Aspects of diffusion in the stadium billiard.
AB  - We perform a detailed numerical study of diffusion in the E stadium of
      Bunimovich, and propose an empirical model of the local and global diffusion for
      various values of E with the following conclusions: (i) the diffusion is normal
      for all values of E (<=0.3) and all initial conditions, (ii) the diffusion
      constant is a parabolic function of the momentum (i.e., we have inhomogeneous
      diffusion), (iii) the model describes the diffusion very well including the
      boundary effects, (iv) the approach to the asymptotic equilibrium steady state is
      exponential, (v) the so-called random model (Robnik et al., 1997) is confirmed to
      apply very well, (vi) the diffusion constant extracted from the distribution
      function in momentum space and the one derived from the second moment agree very
      well. The classical transport time, an important parameter in quantum chaos, is
      thus determined.

PMID- 29448324
TI  - Scaling properties of dynamical localization in monochromatically perturbed
      quantum maps: Standard map and Anderson map.
AB  - Dynamical localization phenomena of monochromatically perturbed standard map (SM)
      and Anderson map (AM), which are both identified with a two-dimensional
      disordered system under suitable conditions, are investigated by the numerical
      wave-packet propagation. Some phenomenological formula of the dynamical
      localization length valid for wide range of control parameters are proposed for
      both SM and AM. For SM the formula completely agree with the experimental
      formula, and for AM the presence of a new regime of localization is confirmed.
      These formula can be derived by the self-consistent mean-field theory of Anderson
      localization on the basis of a new hypothesis for the cut-off length. Transient
      diffusion in the large limit of the localization length is also discussed.

PMID- 29448325
TI  - Subsystem eigenstate thermalization hypothesis.
AB  - Motivated by the qualitative picture of canonical typicality, we propose a
      refined formulation of the eigenstate thermalization hypothesis (ETH) for chaotic
      quantum systems. This formulation, which we refer to as subsystem ETH, is in
      terms of the reduced density matrix of subsystems. This strong form of ETH
      outlines the set of observables defined within the subsystem for which it
      guarantees eigenstate thermalization. We discuss the limits when the size of the
      subsystem is small or comparable to its complement. In the latter case we outline
      the way to calculate the leading volume-proportional contribution to the von
      Neumann and Renyi entanglment entropies. Finally, we provide numerical evidence
      for the proposal in the case of a one-dimensional Ising spin chain.

PMID- 29448326
TI  - Characterization of maximally random jammed sphere packings. III. Transport and
      electromagnetic properties via correlation functions.
AB  - In the first two papers of this series, we characterized the structure of
      maximally random jammed (MRJ) sphere packings across length scales by computing a
      variety of different correlation functions, spectral functions, hole
      probabilities, and local density fluctuations. From the remarkable structural
      features of the MRJ packings, especially its disordered hyperuniformity,
      exceptional physical properties can be expected. Here we employ these structural
      descriptors to estimate effective transport and electromagnetic properties via
      rigorous bounds, exact expansions, and accurate analytical approximation
      formulas. These property formulas include interfacial bounds as well as universal
      scaling laws for the mean survival time and the fluid permeability. We also
      estimate the principal relaxation time associated with Brownian motion among
      perfectly absorbing traps. For the propagation of electromagnetic waves in the
      long-wavelength limit, we show that a dispersion of dielectric MRJ spheres within
      a matrix of another dielectric material forms, to a very good approximation, a
      dissipationless disordered and isotropic two-phase medium for any phase
      dielectric contrast ratio. We compare the effective properties of the MRJ sphere
      packings to those of overlapping spheres, equilibrium hard-sphere packings, and
      lattices of hard spheres. Moreover, we generalize results to micro- and
      macroscopically anisotropic packings of spheroids with tensorial effective
      properties. The analytic bounds predict the qualitative trend in the physical
      properties associated with these structures, which provides guidance to more time
      consuming simulations and experiments. They especially provide impetus for
      experiments to design materials with unique bulk properties resulting from
      hyperuniformity, including structural-color and color-sensing applications.

PMID- 29448327
TI  - Thin structure of the transit time distributions of open billiards.
AB  - It is known that typical open billiards distribution of transit times is an
      exponentially decaying function, possibly with a power-law tail. In the paper we
      show that on small scales some of such distributions change their appearance.
      These distributions contain a quasiperiodic thin structure, which carries a
      significant amount of information about the system. Origin and properties of this
      structure are discussed.

PMID- 29448328
TI  - Granular response to impact: Topology of the force networks.
AB  - The impact of an intruder on granular matter leads to the formation of mesoscopic
      force networks, which were seen particularly clearly in the recent experiments
      carried out with photoelastic particles [Clark et al., Phys. Rev. Lett. 114,
      144502 (2015)PRLTAO0031-900710.1103/PhysRevLett.114.144502]. These force networks
      are characterized by complex structure and evolve on fast time scales. While it
      is known that total photoelastic activity in the granular system is correlated
      with the acceleration of the intruder, it is not known how the structure of the
      force network evolves during impact, and if there are dominant features in the
      networks that can be used to describe the intruder's dynamics. Here, we use
      topological tools, in particular persistent homology, to describe these features.
      Persistent homology allows quantification of both structure and time evolution of
      the resulting force networks. We find that there is a clear correlation of the
      intruder's dynamics and some of the topological measures implemented. This
      finding allows us to discuss which properties of the force networks are most
      important when attempting to describe the intruder's dynamics. In particular, we
      find that the presence of loops in the force network, quantified by persistent
      homology, is strongly correlated to the deceleration of the intruder. In some
      cases, particularly for the impact on soft particles, the measures derived from
      the persistence analysis describe the deceleration of the intruder even better
      than the total photoelastic activity. We are also able to define an upper bound
      on the relevant time scale over which the force networks evolve.

PMID- 29448329
TI  - Minimum energy dissipation required for a logically irreversible operation.
AB  - According to Landauer's principle, the minimum heat emission required for
      computing is linked to logical entropy, or logical reversibility. The validity of
      Landauer's principle has been investigated for several decades and was finally
      demonstrated in recent experiments by showing that the minimum heat emission is
      associated with the reduction in logical entropy during a logically irreversible
      operation. Although the relationship between minimum heat emission and logical
      reversibility is being revealed, it is not clear how much free energy is required
      to be dissipated for a logically irreversible operation. In the present study, in
      order to reveal the connection between logical reversibility and free energy
      dissipation, we numerically demonstrated logically irreversible protocols using
      adiabatic superconductor logic. The calculation results of work during the
      protocol showed that, while the minimum heat emission conforms to Landauer's
      principle, the free energy dissipation can be arbitrarily reduced by performing
      the protocol quasistatically. The above results show that logical reversibility
      is not associated with thermodynamic reversibility, and that heat is not only
      emitted from logic devices but also absorbed by logic devices. We also formulated
      the heat emission from adiabatic superconductor logic during a logically
      irreversible operation at a finite operation speed.

PMID- 29448330
TI  - Structural behavior of supercritical fluids under confinement.
AB  - The existence of the Frenkel line in the supercritical regime of a Lennard-Jones
      (LJ) fluid shown through molecular dynamics (MD) simulations initially and later
      corroborated by experiments on argon opens up possibilities of understanding the
      structure and dynamics of supercritical fluids in general and of the Frenkel line
      in particular. The location of the Frenkel line, which demarcates two distinct
      physical states, liquidlike and gaslike within the supercritical regime, has been
      established through MD simulations of the velocity autocorrelation (VACF) and
      radial distribution function (RDF). We, in this article, explore the changes in
      the structural features of supercritical LJ fluid under partial confinement using
      atomistic walls. The study is carried out across the Frenkel line through a
      series of MD simulations considering a set of thermodynamics states in the
      supercritical regime (P=5000 bar, 240K<=T<=1500K) of argon well above the
      critical point. Confinement is partial, with atomistic walls located normal to z
      and extending to "infinity" along the x and y directions. In the "liquidlike"
      regime of the supercritical phase, particles are found to be distributed in
      distinct layers along the z axis with layer spacing less than one atomic diameter
      and the lateral RDF showing amorphous-like structure for specific spacings
      (packing frustration) and non-amorphous-like structure for other spacings.
      Increasing the rigidity of the atomistic walls is found to lead to stronger
      layering and increased structural order. For confinement with reflective walls,
      layers are found to form with one atomic diameter spacing and the lateral RDF
      showing close-packed structure for the smaller confinements. Translational order
      parameter and excess entropy assessment confirms the ordering taking place for
      atomistic wall and reflective wall confinements. In the "gaslike" regime of the
      supercritical phase, particle distribution along the spacing and the lateral RDF
      exhibit features not significantly different from that due to normal gas regime.
      The heterogeneity across the Frenkel line, found to be present both in bulk and
      confined systems, might cause the breakdown of the universal scaling between
      structure and dynamics of fluids necessitating the determination of a unique
      relationship between them.

PMID- 29448331
TI  - Fractional dynamics using an ensemble of classical trajectories.
AB  - A trajectory-based formulation for fractional dynamics is presented and the
      trajectories are generated deterministically. In this theoretical framework, we
      derive a new class of estimators in terms of confluent hypergeometric function
      (_{1}F_{1}) to represent the Riesz fractional derivative. Using this method, the
      simulation of free and confined Levy flight are in excellent agreement with the
      exact numerical and analytical results. In addition, the barrier crossing in a
      bistable potential driven by Levy noise of index alpha is investigated. In phase
      space, the behavior of trajectories reveal the feature of Levy flight in a better
      perspective.

PMID- 29448332
TI  - Looking for the optimal rate of recombination for evolutionary dynamics.
AB  - We consider many-site mutation-recombination models of evolution with selection.
      We are looking for situations where the recombination increases the mean fitness
      of the population, and there is an optimal recombination rate. We found two
      fitness landscapes supporting such nonmonotonic behavior of the mean fitness
      versus the recombination rate. The first case is related to the evolution near
      the error threshold on a neutral-network-like fitness landscape, for moderate
      genome lengths and large population. The more realistic case is the second one,
      in which we consider the evolutionary dynamics of a finite population on a rugged
      fitness landscape (the smooth fitness landscape plus some random contributions to
      the fitness). We also give the solution to the horizontal gene transfer model in
      the case of asymmetric mutations. To obtain nonmonotonic behavior for both
      mutation and recombination, we need a specially designed (ideal) fitness
      landscape.

PMID- 29448333
TI  - Absolute and convective instabilities of a film flow down a vertical fiber
      subjected to a radial electric field.
AB  - We consider the motion of a gravity-driven flow down a vertical fiber subjected
      to a radial electric field. This flow exhibits rich dynamics including the
      formation of droplets, or beads, driven by a Rayleigh-Plateau mechanism modified
      by the presence of gravity as well as the Maxwell stress at the interface. A
      spatiotemporal stability analysis is performed to investigate the effect of
      electric field on the absolute-convective instability (AI-CI) characteristics. We
      performed a numerical simulation on the nonlinear evolution of the film to
      examine the transition from CI to AI regime. The numerical results are in
      excellent agreement with the spatiotemporal stability analysis. The blowup
      behavior of nonlinear simulation predicts the formation of touchdown singularity
      of the interface due to the effect of electric field. We try to connect the
      blowup behavior with the AI-CI characteristics. It is found that the
      singularities mainly occur in the AI regime. The results indicate that the film
      may have a tendency to form very sharp tips due to the enhancement of the
      absolute instability induced by the electric field. We perform a theoretical
      analysis to study the behaviors of the singularities. The results show that there
      exists a self-similarity between the temporal and spatial distances from the
      singularities.

PMID- 29448334
TI  - Metastable states and energy flow pathway in square graphene resonators.
AB  - Nonlinear interaction between flexural modes is critical to heat conductivity and
      mechanical vibration of two-dimensional materials such as graphene. Much effort
      has been devoted to understand the underlying mechanism. In this paper, we
      examine solely the out-of-plane flexural modes and identify their energy flow
      pathway during thermalization process. The key is the development of a universal
      scheme that numerically characterizes the strength of nonlinear interactions
      between normal modes. In particular, for our square graphene system, the modes
      are grouped into four classes by their distinct symmetries. The couplings are
      significantly larger within a class than between classes. As a result, the
      equations for the normal modes in the same class as the initially excited one can
      be approximated by driven harmonic oscillators, therefore, they get energy almost
      instantaneously. Because of the hierarchical organization of the mode coupling,
      the energy distribution among the modes will arrive at a stable profile, where
      most of the energy is localized on a few modes, leading to the formation of
      "natural package" and metastable states. The dynamics for modes in other symmetry
      classes follows a Mathieu type of equation, thus, interclass energy flow, when
      the initial excitation energy is small, starts typically when there is a mode
      that lies in the unstable region in the parameter space of Mathieu equation. Due
      to strong coupling of the modes inside the class, the whole class will get energy
      and be lifted up by the unstable mode. This characterizes the energy flow pathway
      of the system. These results bring fundamental understandings to the Fermi-Pasta
      Ulam problem in two-dimensional systems with complex potentials, and reveal
      clearly the physical picture of dynamical interactions between the flexural
      modes, which will be crucial to the understanding of their abnormal contribution
      to heat conduction and nonlinear mechanical vibrations.

PMID- 29448335
TI  - Zealots in the mean-field noisy voter model.
AB  - The influence of zealots on the noisy voter model is studied theoretically and
      numerically at the mean-field level. The noisy voter model is a modification of
      the voter model that includes a second mechanism for transitions between states:
      Apart from the original herding processes, voters may change their states because
      of an intrinsic noisy-in-origin source. By increasing the importance of the noise
      with respect to the herding, the system exhibits a finite-size phase transition
      from a quasiconsensus state, where most of the voters share the same opinion, to
      one with coexistence. Upon introducing some zealots, or voters with fixed
      opinion, the latter scenario may change significantly. We unveil new situations
      by carrying out a systematic numerical and analytical study of a fully connected
      network for voters, but allowing different voters to be directly influenced by
      different zealots. We show that this general system is equivalent to a system of
      voters without zealots, but with heterogeneous values of their parameters
      characterizing herding and noisy dynamics. We find excellent agreement between
      our analytical and numerical results. Noise and herding or zealotry acting
      together in the voter model yields a nontrivial mixture of the scenarios with the
      two mechanisms acting alone: It represents a situation where the global-local
      (noise-herding) competition is coupled to a symmetry breaking (zealots). In
      general, the zealotry enhances the effective noise of the system, which may
      destroy the original quasiconsensus state, and can introduce a bias towards the
      opinion of the majority of zealots, hence breaking the symmetry of the system and
      giving rise to new phases. In the most general case we find two different
      transitions: a discontinuous transition from an asymmetric bimodal phase to an
      extreme asymmetric phase and a second continuous transition from the extreme
      asymmetric phase to an asymmetric unimodal phase.

PMID- 29448336
TI  - Synchronization in networks with heterogeneous coupling delays.
AB  - Synchronization in networks of identical oscillators with heterogeneous coupling
      delays is studied. A decomposition of the network dynamics is obtained by block
      diagonalizing a newly introduced adjacency lag operator which contains the
      topology of the network as well as the corresponding coupling delays. This
      generalizes the master stability function approach, which was developed for
      homogenous delays. As a result the network dynamics can be analyzed by delay
      differential equations with distributed delay, where different delay
      distributions emerge for different network modes. Frequency domain methods are
      used for the stability analysis of synchronized equilibria and synchronized
      periodic orbits. As an example, the synchronization behavior in a system of delay
      coupled Hodgkin-Huxley neurons is investigated. It is shown that the parameter
      regions where synchronized periodic spiking is unstable expand when increasing
      the delay heterogeneity.

PMID- 29448337
TI  - Accurate analytic solution of chemical master equations for gene regulation
      networks in a single cell.
AB  - Studying gene regulation networks in a single cell is an important, interesting,
      and hot research topic of molecular biology. Such process can be described by
      chemical master equations (CMEs). We propose a Hamilton-Jacobi equation method
      with finite-size corrections to solve such CMEs accurately at the intermediate
      region of switching, where switching rate is comparable to fast protein
      production rate. We applied this approach to a model of self-regulating proteins
      [H. Ge et al., Phys. Rev. Lett. 114, 078101 (2015)PRLTAO0031
      900710.1103/PhysRevLett.114.078101] and found that as a parameter related to
      inducer concentration increases the probability of protein production changes
      from unimodal to bimodal, then to unimodal, consistent with phenotype switching
      observed in a single cell.

PMID- 29448338
TI  - Thin film modeling of crystal dissolution and growth in confinement.
AB  - We present a continuum model describing dissolution and growth of a crystal
      contact confined against a substrate. Diffusion and hydrodynamics in the liquid
      film separating the crystal and the substrate are modeled within the lubrication
      approximation. The model also accounts for the disjoining pressure and surface
      tension. Within this framework, we obtain evolution equations which govern the
      nonequilibrium dynamics of the crystal interface. Based on this model, we explore
      the problem of dissolution under an external load, known as pressure solution. We
      find that in steady state, diverging (power-law) crystal-surface repulsions lead
      to flat contacts with a monotonic increase of the dissolution rate as a function
      of the load. Forces induced by viscous dissipation then surpass those due to
      disjoining pressure at large enough loads. In contrast, finite repulsions
      (exponential) lead to sharp pointy contacts with a dissolution rate independent
      of the load and the liquid viscosity. Ultimately, in steady state, the crystal
      never touches the substrate when pressed against it. This result is independent
      from the nature of the crystal-surface interaction due to the combined effects of
      viscosity and surface tension.

PMID- 29448339
TI  - Cooperative behavior of molecular motions giving rise to two glass transitions in
      the same supercooled mesophase of a smectogenic liquid crystal dimer.
AB  - In the present work, a detailed analysis of the glassy behavior and the
      relaxation dynamics of the liquid crystal dimer alpha-(4-cyanobiphenyl-4'-yloxy)
      omega-(1-pyrenimine-benzylidene-4'-oxy) heptane (CBO7O.Py) throughout both
      nematic and smectic-A mesophases by means of broadband dielectric spectroscopy
      has been performed. CBO7O.Py shows three different dielectric relaxation modes
      and two glass transition (T_{g}) temperatures: The higher T_{g} is due to the
      freezing of the molecular motions responsible for the relaxation mode with the
      lowest frequency (MU_{1L}); the lower T_{g} is due to the motions responsible for
      the two relaxation modes with highest frequencies (MU_{1H} and MU_{2}), which
      converge just at their corresponding T_{g}. It is shown how the three modes
      follow a critical-like description via the dynamic scaling model. The two modes
      with lowest frequencies (MU_{1L} and MU_{1H}) are cooperative in the whole range
      of the mesophases, whereas the highest frequency mode (MU_{2}) is cooperative
      just below some crossover temperature. In terms of fragility, at the glass
      transition, the ensemble (MU_{1H}+MU_{2}) presents a value of the steepness index
      and MU_{1L} a different one, meaning that fragility is a property intrinsic to
      the molecular motion itself. Finally, the steepness index seems to have a
      universal behavior with temperature for the dielectric relaxation modes of liquid
      crystal dimers, being almost constant at high temperatures and increasing
      drastically when cooling the compound down to the glass transition from a
      temperature about 3/4T_{NI}.

PMID- 29448340
TI  - Breathing pulses in the damped-soliton model for nerves.
AB  - Unlike the Hodgkin-Huxley picture in which the nerve impulse results from ion
      exchanges across the cell membrane through ion-gate channels, in the so-called
      soliton model the impulse is seen as an electromechanical process related to
      thermodynamical phenomena accompanying the generation of the action potential. In
      this work, account is taken of the effects of damping on the nerve impulse
      propagation, within the framework of the soliton model. Applying the reductive
      perturbation expansion on the resulting KdV-Burgers equation, a damped nonlinear
      Schrodinger equation is derived and shown to admit breathing-type solitary wave
      solutions. Under specific constraints, these breathing pulse solitons become self
      trapped structures in which the damping is balanced by nonlinearity such that the
      pulse amplitude remains unchanged even in the presence of damping.

PMID- 29448341
TI  - Interstitial micelles in binary blends of ABA triblock copolymers and
      homopolymers.
AB  - We investigate triblock-homopolymer blends of types A1BA2/A and A1BA2/B, using a
      lattice Monte Carlo method. While the simulated triblock chains are
      compositionally symmetric in terms of the A-to-B volume ratio, the A1 block is
      significantly shorter than the A2 block. For the pure A1BA2 melt and the A1BA2
      solutions in selective solvent the phase behavior is relatively well known,
      including existence and stability of the interstitial micelles which were
      discovered in previous Monte Carlo simulations. In this paper we study the
      stability of the interstitial micelles as a function of triblock volume fraction
      in selective homopolymers of either type A or type B, using two significantly
      different homopolymer chain lengths. We found that adding selective homopolymer
      of type A shifts the stability of the interstitial micelles into significantly
      higher temperatures. We also obtained, via self-assembly, intriguing new
      nanostructures which can be identified as ordered truncated octahedra. Finally,
      we established that the phase behavior of the triblock-homopolymer blends depends
      relatively weakly on the chain length of the added homopolymer.

PMID- 29448342
TI  - Heterogeneous continuous-time random walks.
AB  - We introduce a heterogeneous continuous-time random walk (HCTRW) model as a
      versatile analytical formalism for studying and modeling diffusion processes in
      heterogeneous structures, such as porous or disordered media, multiscale or
      crowded environments, weighted graphs or networks. We derive the exact form of
      the propagator and investigate the effects of spatiotemporal heterogeneities onto
      the diffusive dynamics via the spectral properties of the generalized transition
      matrix. In particular, we show how the distribution of first-passage times
      changes due to local and global heterogeneities of the medium. The HCTRW
      formalism offers a unified mathematical language to address various diffusion
      reaction problems, with numerous applications in material sciences, physics,
      chemistry, biology, and social sciences.

PMID- 29448343
TI  - Mutual influence of molecular diffusion in gas and surface phases.
AB  - We develop molecular transport simulation methods that simultaneously deal with
      gas- and surface-phase diffusions to determine the effect of surface diffusion on
      the overall diffusion coefficients. The phenomenon of surface diffusion is
      incorporated into the test particle method and the mean square displacement
      method, which are typically employed only for gas-phase transport. It is found
      that for a simple cylindrical pore, the diffusion coefficients in the presence of
      surface diffusion calculated by these two methods show good agreement. We also
      confirm that both methods reproduce the analytical solution. Then, the diffusion
      coefficients for ink-bottle-shaped pores are calculated using the developed
      method. Our results show that surface diffusion assists molecular transport in
      the gas phase. Moreover, the surface tortuosity factor, which is known to be
      uniquely determined by physical structure, is influenced by the presence of gas
      phase diffusion. This mutual influence of gas-phase diffusion and surface
      diffusion indicates that their simultaneous calculation is necessary for an
      accurate evaluation of the diffusion coefficients.

PMID- 29448344
TI  - Multiple eigenmodes of the Rayleigh-Taylor instability observed for a fluid
      interface with smoothly varying density.
AB  - In this article, multiple eigen-systems including linear growth rates and eigen
      functions have been discovered for the Rayleigh-Taylor instability (RTI) by
      numerically solving the Sturm-Liouville eigen-value problem in the case of two
      dimensional plane geometry. The system called the first mode has the maximal
      linear growth rate and is just extensively studied in literature. Higher modes
      have smaller eigen-values, but possess multi-peak eigen-functions which bring on
      multiple pairs of vortices in the vorticity field. A general fitting expression
      for the first four eigen-modes is presented. Direct numerical simulations show
      that high modes lead to appearances of multi-layered spike-bubble pairs, and lots
      of secondary spikes and bubbles are also generated due to the interactions
      between internal spikes and bubbles. The present work has potential applications
      in many research and engineering areas, e.g., in reducing the RTI growth during
      capsule implosions in inertial confinement fusion.

PMID- 29448345
TI  - Route from discreteness to the continuum for the Tsallis q-entropy.
AB  - The existence and exact form of the continuum expression of the discrete
      nonlogarithmic q-entropy is an important open problem in generalized
      thermostatistics, since its possible lack implies that nonlogarithmic q-entropy
      is irrelevant for the continuous classical systems. In this work, we show how the
      discrete nonlogarithmic q-entropy in fact converges in the continuous limit and
      the negative of the q-entropy with continuous variables is demonstrated to lead
      to the (Csiszar type) q-relative entropy just as the relation between the
      continuous Boltzmann-Gibbs expression and the Kullback-Leibler relative entropy.
      As a result, we conclude that there is no obstacle for the applicability of the q
      entropy to the continuous classical physical systems.

PMID- 29448346
TI  - Exceptional points near first- and second-order quantum phase transitions.
AB  - We study the impact of quantum phase transitions (QPTs) on the distribution of
      exceptional points (EPs) of the Hamiltonian in the complex-extended parameter
      domain. Analyzing first- and second-order QPTs in the Lipkin-Meshkov-Glick model
      we find an exponentially and polynomially close approach of EPs to the respective
      critical point with increasing size of the system. If the critical Hamiltonian is
      subject to random perturbations of various kinds, the averaged distribution of
      EPs close to the critical point still carries decisive information on the QPT
      type. We therefore claim that properties of the EP distribution represent a
      parametrization-independent signature of criticality in quantum systems.

PMID- 29448347
TI  - Analyzing a stochastic process driven by Ornstein-Uhlenbeck noise.
AB  - A scalar Langevin-type process X(t) that is driven by Ornstein-Uhlenbeck noise
      eta(t) is non-Markovian. However, the joint dynamics of X and eta is described by
      a Markov process in two dimensions. But even though there exists a variety of
      techniques for the analysis of Markov processes, it is still a challenge to
      estimate the process parameters solely based on a given time series of X. Such a
      partially observed 2D process could, e.g., be analyzed in a Bayesian framework
      using Markov chain Monte Carlo methods. Alternatively, an embedding strategy can
      be applied, where first the joint dynamics of X and its temporal derivative
      X[over ] is analyzed. Subsequently, the results can be used to determine the
      process parameters of X and eta. In this paper, we propose a more direct approach
      that is purely based on the moments of the increments of X, which can be
      estimated for different time-increments tau from a given time series. From a
      stochastic Taylor expansion of X, analytic expressions for these moments can be
      derived, which can be used to estimate the process parameters by a regression
      strategy.

PMID- 29448348
TI  - Quantum work relations and response theory in parity-time-symmetric quantum
      systems.
AB  - In this work, we show that a universal quantum work relation for a quantum system
      driven arbitrarily far from equilibrium extends to a parity-time- (PT-) symmetric
      quantum system with unbroken PT symmetry, which is a consequence of microscopic
      reversibility. The quantum Jarzynski equality, linear response theory, and
      Onsager reciprocal relations for the PT-symmetric quantum system are recovered as
      special cases of the universal quantum work relation in a PT-symmetric quantum
      system. In the regime of broken PT symmetry, the universal quantum work relation
      does not hold because the norm is not preserved during the dynamics.

PMID- 29448349
TI  - Transmission coefficient from generalized Cantor-like potentials and its
      multifractality.
AB  - We study the scattering problem at generalized Cantor-like potentials
      characterized by the expansion rate a and duplication number N, and derive an
      exact formula of transmittance. It was found that the transmittance is expressed
      with Chebyshev polynomials of the second kind, and the multifractality of the
      reflectance varies depending on a and N.

PMID- 29448351
TI  - Experimental investigation of the glass transition of polystyrene thin films in a
      broad frequency range.
AB  - In this study, we investigate the alpha process of a polystyrene thin film using
      inelastic neutron scattering (INS), dielectric relaxation spectroscopy (DRS), and
      thermal expansion spectroscopy (TES). The DRS and TES measurements exhibited a
      decrease in glass transition temperature (T_{g}) with film thickness. On the
      other hand, an increase in T_{g} was observed in INS studies. In order to
      interpret this contradiction, we investigated the temperature dependence of the
      peak frequency (f_{m}) of the alpha process probed by DRS and TES. The
      experiments revealed an increase in the peak frequency (f_{m}) with decreasing
      film thickness in the frequency region. This observation is consistent with the
      observed decrease in T_{g} with thickness. Interestingly, the increase in T_{g}
      with film thickness was confirmed by fitting the temperature dependence
      measurements of the peak frequency with the Vogel-Fulcher-Tammann equation,
      within the frequency region probed by INS. The discrepancy between INS and DRS or
      TES descriptions of the alpha process is likely to be attributed to a decrease in
      the apparent activation energy with film thickness and reduced mobility, due to
      the impenetrable wall effect.

PMID- 29448350
TI  - Role of spatial heterogeneity in the collective dynamics of cilia beating in a
      minimal one-dimensional model.
AB  - Cilia are elastic hairlike protuberances of the cell membrane found in various
      unicellular organisms and in several tissues of most living organisms. In some
      tissues such as the airway tissues of the lung, the coordinated beating of cilia
      induces a fluid flow of crucial importance as it allows the continuous cleaning
      of our bronchia, known as mucociliary clearance. While most of the models
      addressing the question of collective dynamics and metachronal wave consider
      homogeneous carpets of cilia, experimental observations rather show that cilia
      clusters are heterogeneously distributed over the tissue surface. The purpose of
      this paper is to investigate the role of spatial heterogeneity on the coherent
      beating of cilia using a very simple one-dimensional model for cilia known as the
      rower model. We systematically study systems consisting of a few rowers to
      hundreds of rowers and we investigate the conditions for the emergence of
      collective beating. When considering a small number of rowers, a phase drift
      occurs, hence, a bifurcation in beating frequency is observed as the distance
      between rower clusters is changed. In the case of many rowers, a distribution of
      frequencies is observed. We found in particular the pattern of the patchy
      structure that shows the best robustness in collective beating behavior, as the
      density of cilia is varied over a wide range.

PMID- 29448352
TI  - Insensitivity of active nematic liquid crystal dynamics to topological
      constraints.
AB  - Confining a liquid crystal imposes topological constraints on the orientational
      order, allowing global control of equilibrium systems by manipulation of
      anchoring boundary conditions. In this article, we investigate whether a similar
      strategy allows control of active liquid crystals. We study a hydrodynamic model
      of an extensile active nematic confined in containers, with different anchoring
      conditions that impose different net topological charges on the nematic director.
      We show that the dynamics are controlled by a complex interplay between
      topological defects in the director and their induced vortical flows. We find
      three distinct states by varying confinement and the strength of the active
      stress: A topologically minimal state, a circulating defect state, and a
      turbulent state. In contrast to equilibrium systems, we find that anchoring
      conditions are screened by the active flow, preserving system behavior across
      different topological constraints. This observation identifies a fundamental
      difference between active and equilibrium materials.

PMID- 29448353
TI  - Compression-driven jamming of athermal frictionless spherocylinders in two
      dimensions.
AB  - We simulate numerically the compression-driven jamming of athermal, frictionless,
      soft-core spherocylinders in two dimensions, for a range of particle aspect
      ratios alpha. We find the critical packing fraction phi_{J}(alpha) for the
      jamming transition and the average number of contacts per particle z_{J}(alpha)
      at jamming. We find that both are nonmonotonic, with a peak at alpha~1. We find
      that configurations at the compression-driven jamming point are always hypostatic
      for all alpha, with z_{J}<z_{iso}=2d_{f}=6 the isostatic value. We show that, for
      moderately elongated spherocylinders, there is no orientational ordering upon
      athermal compression through jamming. We analyze in detail the eigenmodes of the
      dynamical matrix close to the jamming point for a few different values of the
      aspect ratio, from nearly circular to moderately elongated. We find that there
      are low frequency bands containing N(z_{iso}-z_{J})/2 modes, such that the
      frequencies of these modes vanish as phi->phi_{J}. We consider the extended
      versus localized nature of these low frequency modes, and the extent to which
      they involve translational or rotational motion, and find many low frequency
      sliding modes where particles can move with little rotation. We highlight the
      importance of treating side-to-side contacts, along flat sides of the
      spherocylinder, properly for the correct determination of z_{J}. We note the
      singular nature of taking the alpha->0 limit. We discuss the similarities and
      differences with previous work on jammed ellipses and ellipsoids, to illustrate
      the effects that different particle shapes have on configurations at jamming.

PMID- 29448354
TI  - Shear thinning and shear thickening of a confined suspension of vesicles.
AB  - Widely regarded as an interesting model system for studying flow properties of
      blood, vesicles are closed membranes of phospholipids that mimic the cytoplasmic
      membranes of red blood cells. In this study we analyze the rheology of a
      suspension of vesicles in a confined geometry: the suspension, bound by two
      planar rigid walls on each side, is subject to a shear flow. Flow properties are
      then analyzed as a function of shear rate gamma[over ], the concentration of the
      suspension phi, and the viscosity contrast lambda=eta_{in}/eta_{out}, where
      eta_{in} and eta_{out} are the fluid viscosities of the inner and outer fluids,
      respectively. We find that the apparent (or effective viscosity) of the
      suspension exhibits both shear thinning (decreasing viscosity with shear rate) or
      shear thickening (increasing viscosity with shear rate) in the same concentration
      range. The shear thinning or thickening behaviors appear as subtle phenomena,
      dependant on viscosity contrast lambda. We provide physical arguments on the
      origins of these behaviors.

PMID- 29448355
TI  - Binding constant of cell adhesion receptors and substrate-immobilized ligands
      depends on the distribution of ligands.
AB  - Cell-cell adhesion and the adhesion of cells to tissues and extracellular matrix,
      which are pivotal for immune response, tissue development, and cell locomotion,
      depend sensitively on the binding constant of receptor and ligand molecules
      anchored on the apposing surfaces. An important question remains of whether the
      immobilization of ligands affects the affinity of binding with cell adhesion
      receptors. We have investigated the adhesion of multicomponent membranes to a
      flat substrate coated with immobile ligands using Monte Carlo simulations of a
      statistical mesoscopic model with biologically relevant parameters. We find that
      the binding of the adhesion receptors to ligands immobilized on the substrate is
      strongly affected by the ligand distribution. In the case of ligand clusters, the
      receptor-ligand binding constant can be significantly enhanced due to the less
      translational entropy loss of lipid-raft domains in the model cell membranes upon
      the formation of additional complexes. For ligands randomly or uniformly
      immobilized on the substrate, the binding constant is rather decreased since the
      receptors localized in lipid-raft domains have to pay an energetic penalty in
      order to bind ligands. Our findings help to understand why cell-substrate
      adhesion experiments for measuring the impact of lipid rafts on the receptor
      ligand interactions led to contradictory results.

PMID- 29448356
TI  - Two- and three-point functions at criticality: Monte Carlo simulations of the
      improved three-dimensional Blume-Capel model.
AB  - We compute two- and three-point functions at criticality for the three
      dimensional Ising universality class. To this end, we simulate the improved Blume
      Capel model at the critical temperature on lattices of a linear size up to
      L=1600. As a check, also simulations of the spin-1/2 Ising model are performed.
      We find f_{sigmasigmaepsilon}=1.051(1) and f_{epsilonepsilonepsilon}=1.533(5) for
      operator product expansion coefficients. These results are consistent with but
      less precise than those recently obtained by using the bootstrap method. An
      important ingredient in our simulations is a variance reduced estimator of N
      point functions. Finite size corrections vanish with L^{-Delta_{epsilon}}, where
      L is the linear size of the lattice and Delta_{epsilon} is the scaling dimension
      of the leading Z_{2}-even scalar epsilon.

PMID- 29448357
TI  - Oscillating decorated interfaces in parametrically driven systems.
AB  - Macroscopic systems forced by the temporal modulation of their parameters exhibit
      complex interfaces between symmetric states. Here we investigate the origin of
      the transition from a flat to an oscillating decorated interface. Based on a
      model that describes a magnetic plane under the influence of an oscillating
      magnetic field and an extended Josephson junction under the influence of an
      alternating current, we derive a simple model that accounts for the interface
      dynamics. Analytically this model allows us to reveal that this transition is a
      parametric resonance between the frequencies of interface modes and the forcing.
      Numerical simulations of magnetic systems, extended Josephson junctions, and our
      simplified model show quite good agreement.

PMID- 29448358
TI  - Autonomous quantum Maxwell's demon based on two exchange-coupled quantum dots.
AB  - I study an autonomous quantum Maxwell's demon based on two exchange-coupled
      quantum dots attached to the spin-polarized leads. The principle of operation of
      the demon is based on the coherent oscillations between the spin states of the
      system which act as a quantum iSWAP gate. Due to the operation of the iSWAP gate,
      one of the dots acts as a feedback controller which blocks the transport with the
      bias in the other dot, thus inducing the electron pumping against the bias; this
      leads to the locally negative entropy production. Operation of the demon is
      associated with the information transfer between the dots, which is studied
      quantitatively by mapping the analyzed setup onto the thermodynamically
      equivalent auxiliary system. The calculated entropy production in a single
      subsystem and information flow between the subsystems are shown to obey a local
      form of the second law of thermodynamics, similar to the one previously derived
      for classical bipartite systems.

PMID- 29448359
TI  - Simple analysis of scattering data with the Ornstein-Zernike equation.
AB  - In this paper we propose and explore a method of analysis of the scattering
      experimental data for uniform liquidlike systems. In our pragmatic approach we
      are not trying to introduce by hands an artificial small parameter to work out a
      perturbation theory with respect to the known results, e.g., for hard spheres or
      sticky hard spheres (all the more that in the agreement with the notorious Landau
      statement, there is no physical small parameter for liquids). Instead of it being
      guided by the experimental data we are solving the Ornstein-Zernike equation with
      a trial (variational) form of the interparticle interaction potential. To find
      all needed correlation functions this variational input is iterated numerically
      to satisfy the Ornstein-Zernike equation supplemented by a closure relation. Our
      method is developed for spherically symmetric scattering objects, and our numeric
      code is written for such a case. However, it can be extended (at the expense of
      more involved computations and a larger amount of required experimental input
      information) for nonspherical particles. What is important for our approach is
      that it is sufficient to know experimental data in a relatively narrow range of
      the scattering wave vectors (q) to compute the static structure factor in a much
      broader range of q. We illustrate by a few model and real experimental examples
      of the x-ray and neutron scattering data how the approach works.

PMID- 29448360
TI  - Enhancement of large fluctuations to extinction in adaptive networks.
AB  - During an epidemic, individual nodes in a network may adapt their connections to
      reduce the chance of infection. A common form of adaption is avoidance rewiring,
      where a noninfected node breaks a connection to an infected neighbor and forms a
      new connection to another noninfected node. Here we explore the effects of such
      adaptivity on stochastic fluctuations in the susceptible-infected-susceptible
      model, focusing on the largest fluctuations that result in extinction of
      infection. Using techniques from large-deviation theory, combined with a
      measurement of heterogeneity in the susceptible degree distribution at the
      endemic state, we are able to predict and analyze large fluctuations and
      extinction in adaptive networks. We find that in the limit of small rewiring
      there is a sharp exponential reduction in mean extinction times compared to the
      case of zero adaption. Furthermore, we find an exponential enhancement in the
      probability of large fluctuations with increased rewiring rate, even when holding
      the average number of infected nodes constant.

PMID- 29448361
TI  - Bridges in complex networks.
AB  - A bridge in a graph is an edge whose removal disconnects the graph and increases
      the number of connected components. We calculate the fraction of bridges in a
      wide range of real-world networks and their randomized counterparts. We find that
      real networks typically have more bridges than their completely randomized
      counterparts, but they have a fraction of bridges that is very similar to their
      degree-preserving randomizations. We define an edge centrality measure, called
      bridgeness, to quantify the importance of a bridge in damaging a network. We find
      that certain real networks have a very large average and variance of bridgeness
      compared to their degree-preserving randomizations and other real networks.
      Finally, we offer an analytical framework to calculate the bridge fraction and
      the average and variance of bridgeness for uncorrelated random networks with
      arbitrary degree distributions.

PMID- 29448362
TI  - Dynamic phase transition of the Blume-Capel model in an oscillating magnetic
      field.
AB  - We employ numerical simulations and finite-size scaling techniques to investigate
      the properties of the dynamic phase transition that is encountered in the Blume
      Capel model subjected to a periodically oscillating magnetic field. We mainly
      focus on the study of the two-dimensional system for various values of the
      crystal-field coupling in the second-order transition regime. Our results
      indicate that the present nonequilibrium phase transition belongs to the
      universality class of the equilibrium Ising model and allow us to construct a
      dynamic phase diagram, in analogy with the equilibrium case, at least for the
      range of parameters considered. Finally, we present some complementary results
      for the three-dimensional model, where again the obtained estimates for the
      critical exponents fall into the universality class of the corresponding three
      dimensional equilibrium Ising ferromagnet.

PMID- 29448363
TI  - Finite-element lattice Boltzmann simulations of contact line dynamics.
AB  - The lattice Boltzmann method has become one of the standard techniques for
      simulating a wide range of fluid flows. However, the intrinsic coupling of
      momentum and space discretization restricts the traditional lattice Boltzmann
      method to regular lattices. Alternative off-lattice Boltzmann schemes exist for
      both single- and multiphase flows that decouple the velocity discretization from
      the underlying spatial grid. The current study extends the applicability of these
      off-lattice methods by introducing a finite element formulation that enables
      simulating contact line dynamics for partially wetting fluids. This work
      exemplifies the implementation of the scheme and furthermore presents benchmark
      experiments that show the scheme reduces spurious currents at the liquid-vapor
      interface by at least two orders of magnitude compared to a nodal implementation
      and allows for predicting the equilibrium states accurately in the range of
      moderate contact angles.

PMID- 29448364
TI  - Snap-buckling in asymmetrically constrained elastic strips.
AB  - When a flat elastic strip is compressed along its axis, it is bent in one of two
      possible directions via spontaneous symmetry breaking, forming a cylindrical arc.
      This is a phenomenon well known as Euler buckling. When this cylindrical section
      is pushed in the other direction, the bending direction can suddenly reverse.
      This instability is called "snap-through buckling" and is one of the elementary
      shape transitions in a prestressed thin structure. Combining experiments and
      theory, we study snap-buckling of an elastic strip with one end hinged and the
      other end clamped. These asymmetric boundary constraints break the intrinsic
      symmetry of the strip, generating mechanical behaviors, including largely
      hysteretic but reproducible force responses and switchlike discontinuous shape
      changes. We establish the set of exact analytical solutions to fully explain all
      our major experimental and numerical findings. Asymmetric boundary conditions
      arise naturally in diverse situations when a thin object is in contact with a
      solid surface at one end. The introduction of asymmetry through boundary
      conditions yields new insight into complex and programmable functionalities in
      material and industrial design.

PMID- 29448365
TI  - Improved belief propagation algorithm finds many Bethe states in the random-field
      Ising model on random graphs.
AB  - We first present an empirical study of the Belief Propagation (BP) algorithm,
      when run on the random field Ising model defined on random regular graphs in the
      zero temperature limit. We introduce the notion of extremal solutions for the BP
      equations, and we use them to fix a fraction of spins in their ground state
      configuration. At the phase transition point the fraction of unconstrained spins
      percolates and their number diverges with the system size. This in turn makes the
      associated optimization problem highly non trivial in the critical region. Using
      the bounds on the BP messages provided by the extremal solutions we design a new
      and very easy to implement BP scheme which is able to output a large number of
      stable fixed points. On one hand this new algorithm is able to provide the
      minimum energy configuration with high probability in a competitive time. On the
      other hand we found that the number of fixed points of the BP algorithm grows
      with the system size in the critical region. This unexpected feature poses new
      relevant questions about the physics of this class of models.

PMID- 29448366
TI  - Growth-mediated autochemotactic pattern formation in self-propelling bacteria.
AB  - Bacteria, while developing a multicellular colony or biofilm, can undergo pattern
      formation by diverse intricate mechanisms. One such route is directional movement
      or chemotaxis toward or away from self-secreted or externally employed chemicals.
      In some bacteria, the self-produced signaling chemicals or autoinducers
      themselves act as chemoattractants or chemorepellents and thereby regulate the
      directional movements of the cells in the colony. In addition, bacteria follow a
      certain growth kinetics which is integrated in the process of colony development.
      Here, we study the interplay of bacterial growth dynamics, cell motility, and
      autochemotactic motion with respect to the self-secreted diffusive signaling
      chemicals in spatial pattern formation. Using a continuum model of motile
      bacteria, we show growth can act as a crucial tuning parameter in determining the
      spatiotemporal dynamics of a colony. In action of growth dynamics, while
      chemoattraction toward autoinducers creates arrested phase separation, pattern
      transitions and suppression can occur for a fixed chemorepulsive strength.

PMID- 29448367
TI  - First-passage time for superstatistical Fokker-Planck models.
AB  - The first-passage-time (FPT) problem is studied for superstatistical models
      assuming that the mesoscopic system dynamics is described by a Fokker-Planck
      equation. We show that all moments of the random intensive parameter associated
      to the superstatistical approach can be put in one-to-one correspondence with the
      moments of the FPT. For systems subjected to an additional uncorrelated external
      force, the same statistical information is obtained from the dependence of the
      FPT moments on the external force. These results provide an alternative technique
      for checking the validity of superstatistical models. As an example, we
      characterize the mean FPT for a forced Brownian particle.

PMID- 29448368
TI  - Disentangling the role of athermal walls on the Knudsen paradox in molecular and
      granular gases.
AB  - The nature of particle-wall interactions is shown to have a profound impact on
      the well-known "Knudsen paradox" [or the "Knudsen minimum" effect, which refers
      to the decrease of the mass-flow rate of a gas with increasing Knudsen number Kn,
      reaching a minimum at Kn~O(1) and increasing logarithmically with Kn as Kn
      >infinity] in the acceleration-driven Poiseuille flow of rarefied gases. The
      nonmonotonic variation of the flow rate with Kn occurs even in a granular or
      dissipative gas in contact with thermal walls. The latter result is in
      contradiction with recent work [Alam et al., J. Fluid Mech. 782, 99
      (2015)JFLSA70022-112010.1017/jfm.2015.523] that revealed the absence of the
      Knudsen minimum in granular Poiseuille flow for which the flow rate was found to
      decrease at large values of Kn. The above conundrum is resolved by distinguishing
      between "thermal" and "athermal" walls, and it is shown that, for both molecular
      and granular gases, the momentum transfer to athermal walls is much different
      than that to thermal walls which is directly responsible for the anomalous flow
      rate variation with Kn in the rarefied regime. In the continuum limit of Kn->0,
      the athermal walls are shown to be closely related to "no-flux" ("adiabatic")
      walls for which the Knudsen minimum does not exist either. A possible
      characterization of athermal walls in terms of (1) an effective specularity
      coefficient for the slip velocity and (2) a flux-type boundary condition for
      granular temperature is suggested based on simulation results.

PMID- 29448369
TI  - Three-dimensional instabilities for the flow around a heaving foil.
AB  - This paper investigates the three-dimensional instabilities of the flow past a
      periodically heaving airfoil. By comparison with a pitching foil [Deng et al.,
      Phys. Rev. E 92, 063013 (2015)PLEEE81539-375510.1103/PhysRevE.92.063013], here we
      present distinctive characteristics for the heaving foil, particulary regarding
      its Floquet modes. By increasing the frequency (Sr), or equivalently decreasing
      the amplitude (A_{D}) along the marginal stability curve in the (Sr,A_{D}) phase
      space, the critical Floquet mode emerges sequentially as A, quasiperiodic (QP),
      and B. It is interesting to note that both modes A and B are synchronous with the
      base flow, in contrast to the quasiperiodic mode QP. To further investigate the
      instability across the marginal curve, we fix the frequency at Sr=0.187, of which
      the critical Floquet mode is located in the synchronous regime, while varying
      A_{D} around the critical point. We find that the dominant mode switches from
      mode A to mode B, while mode QP never becomes critical as we increase A_{D}. We
      note that mode S, a subharmonic mode, can also be unstable, which, however, is
      not physically realizable, because the magnitude of its Floquet multiplier is
      always smaller than that of mode B. We have also studied the influence of various
      Reynolds numbers at the same critical point on the marginal stability curve, with
      the results resembling that by varying the amplitude A_{D}.

PMID- 29448370
TI  - Rigorous proof for the nonlocal correlation function in the transverse Ising
      model with ring frustration.
AB  - An unusual correlation function was conjectured by Campostrini et al. [Phys. Rev.
      E 91, 042123 (2015)PLEEE81539-375510.1103/PhysRevE.91.042123] for the ground
      state of a transverse Ising chain with geometrical frustration. Later, we
      provided a rigorous proof for it and demonstrated its nonlocal nature based on an
      evaluation of a Toeplitz determinant in the thermodynamic limit [J. Stat. Mech.
      (2016) 11310210.1088/1742-5468/2016/11/113102]. In this paper, we further prove
      that all the low excited energy states forming the gapless kink phase share the
      same asymptotic correlation function with the ground state. As a consequence, the
      thermal correlation function almost remains constant at low temperatures if one
      assumes a canonical ensemble.

PMID- 29448371
TI  - Decoherence approach to energy transfer and work done by slowly driven systems.
AB  - A main problem, which is met when computing the energy transfer of or work done
      by a quantum system, comes from the fact that the system may lie in states with
      coherence in its energy eigenstates. As is well known, when the so-called
      environment-induced decoherence has happened with respect to a preferred basis
      given by the energy basis, no coherence exists among the energy basis and the
      energy change of the system can be computed in a definite way. I argue that one
      may make use of this property, in the search for an appropriate definition of
      quantum work for a total system that does not include any measuring apparatus. To
      show how this idea may work, in this paper, I study decoherence properties of a
      generic slowly driven system, which is weakly coupled to a huge environment whose
      main body is a complex quantum system. It is shown that decoherence may
      generically happen for such a system.

PMID- 29448372
TI  - Quantum theory for the dynamic structure factor in correlated two-component
      systems in nonequilibrium: Application to x-ray scattering.
AB  - We present a quantum theory for the dynamic structure factors in nonequilibrium,
      correlated, two-component systems such as plasmas or warm dense matter. The
      polarization function, which is needed as the input for the calculation of the
      structure factors, is calculated in nonequilibrium based on a perturbation
      expansion in the interaction strength. To make our theory applicable for x-ray
      scattering, a generalized Chihara decomposition for the total electron structure
      factor in nonequilibrium is derived. Examples are given and the influence of
      correlations and exchange on the structure and the x-ray-scattering spectrum are
      discussed for a model nonequilibrium distribution, as often encountered during
      laser heating of materials, as well as for two-temperature systems.

PMID- 29448373
TI  - Optimal performance of generalized heat engines with finite-size baths of
      arbitrary multiple conserved quantities beyond independent-and-identical
      distribution scaling.
AB  - In quantum thermodynamics, effects of finiteness of the baths have been less
      considered. In particular, there is no general theory which focuses on finiteness
      of the baths of multiple conserved quantities. Then, we investigate how the
      optimal performance of generalized heat engines with multiple conserved
      quantities alters in response to the size of the baths. In the context of general
      theories of quantum thermodynamics, the size of the baths has been given in terms
      of the number of identical copies of a system, which does not cover even such a
      natural scaling as the volume. In consideration of the asymptotic extensivity, we
      deal with a generic scaling of the baths to naturally include the volume scaling.
      Based on it, we derive a bound for the performance of generalized heat engines
      reflecting finite-size effects of the baths, which we call fine-grained
      generalized Carnot bound. We also construct a protocol to achieve the optimal
      performance of the engine given by this bound. Finally, applying the obtained
      general theory, we deal with simple examples of generalized heat engines. As for
      an example of non-independent-and-identical-distribution scaling and multiple
      conserved quantities, we investigate a heat engine with two baths composed of an
      ideal gas exchanging particles, where the volume scaling is applied. The result
      implies that the mass of the particle explicitly affects the performance of this
      engine with finite-size baths.

PMID- 29448374
TI  - Characterizing real-space topology in Rice-Mele model by thermodynamics.
AB  - The thermodynamic quantities which are related to energy-level statistics are
      used to characterize the real-space topology of the Rice-Mele model. Through
      studying the energy spectrum of the model under different boundary conditions, we
      found that the non-normalizable wave function for the infinite domain is reduced
      to the edge state adhered to the boundary. For the finite domain with symmetric
      boundary condition, the critical point for the topological phase transition is
      equal to the inverse of the domain length. In contrast, the critical point is
      zero for the semi-infinite domain. Additionally, the symmetry of the energy
      spectrum is found to be sensitive to the boundary conditions of the Rice-Mele
      model, and the emergence of the edge states as well as the topological phase
      transition can be reflected in the thermodynamic properties. A potentially
      practical scheme is proposed for simulating the Rice-Mele model and detecting the
      relevant thermodynamic quantities in the context of Bose-Einstein condensate.

PMID- 29448375
TI  - Natural extension of fast-slow decomposition for dynamical systems.
AB  - Modeling and parameter estimation to capture the dynamics of physical systems are
      often challenging because many parameters can range over orders of magnitude and
      are difficult to measure experimentally. Moreover, selecting a suitable model
      complexity requires a sufficient understanding of the model's potential use, such
      as highlighting essential mechanisms underlying qualitative behavior or precisely
      quantifying realistic dynamics. We present an approach that can guide model
      development and tuning to achieve desired qualitative and quantitative solution
      properties. It relies on the presence of disparate time scales and employs
      techniques of separating the dynamics of fast and slow variables, which are well
      known in the analysis of qualitative solution features. We build on these methods
      to show how it is also possible to obtain quantitative solution features by
      imposing designed dynamics for the slow variables in the form of specified two
      dimensional paths in a bifurcation-parameter landscape.

PMID- 29448376
TI  - Matrix product algorithm for stochastic dynamics on networks applied to
      nonequilibrium Glauber dynamics.
AB  - We introduce and apply an efficient method for the precise simulation of
      stochastic dynamical processes on locally treelike graphs. Networks with cycles
      are treated in the framework of the cavity method. Such models correspond, for
      example, to spin-glass systems, Boolean networks, neural networks, or other
      technological, biological, and social networks. Building upon ideas from quantum
      many-body theory, our approach is based on a matrix product approximation of the
      so-called edge messages-conditional probabilities of vertex variable
      trajectories. Computation costs and accuracy can be tuned by controlling the
      matrix dimensions of the matrix product edge messages (MPEM) in truncations. In
      contrast to Monte Carlo simulations, the algorithm has a better error scaling and
      works for both single instances as well as the thermodynamic limit. We employ it
      to examine prototypical nonequilibrium Glauber dynamics in the kinetic Ising
      model. Because of the absence of cancellation effects, observables with small
      expectation values can be evaluated accurately, allowing for the study of decay
      processes and temporal correlations.

PMID- 29448377
TI  - Curvature by design and on demand in liquid crystal elastomers.
AB  - The shape of liquid crystalline elastomers (LCEs) with spatial variation in the
      director orientation can be transformed by exposure to a stimulus. Here, informed
      by previously reported analytical treatments, we prepare complex spiral patterns
      imprinted into LCEs and quantify the resulting shape transformation.
      Quantification of the stimuli-induced shapes reveals good agreement between
      predicted and experimentally observed curvatures. We conclude this communication
      by reporting a design strategy to allow LCE films to be anchored at their
      external boundaries onto rigid substrates without incurring internal, mechanical
      mismatch stresses upon actuation, a critical advance to the realization of shape
      transformation of LCEs in practical device applications.

PMID- 29448378
TI  - Memory effects for a stochastic fractional oscillator in a magnetic field.
AB  - The problem of random motion of harmonically trapped charged particles in a
      constant external magnetic field is studied. A generalized three-dimensional
      Langevin equation with a power-law memory kernel is used to model the interaction
      of Brownian particles with the complex structure of viscoelastic media (e.g.,
      dusty plasmas). The influence of a fluctuating environment is modeled by an
      additive fractional Gaussian noise. In the long-time limit the exact expressions
      of the first-order and second-order moments of the fluctuating position for the
      Brownian particle subjected to an external periodic force in the plane
      perpendicular to the magnetic field have been calculated. Also, the particle's
      angular momentum is found. It is shown that an interplay of external periodic
      forcing, memory, and colored noise can generate a variety of cooperation effects,
      such as memory-induced sign reversals of the angular momentum, multiresonance
      versus Larmor frequency, and memory-induced particle confinement in the absence
      of an external trapping field. Particularly in the case without external
      trapping, if the memory exponent is lower than a critical value, we find a
      resonancelike behavior of the anisotropy in the particle position distribution
      versus the driving frequency, implying that it can be efficiently excited by an
      oscillating electric field. Similarities and differences between the behaviors of
      the models with internal and external noises are also discussed.

PMID- 29448379
TI  - Time evolution of intermittency in the passive slider problem.
AB  - How does a steady state with strong intermittency develop in time from an initial
      state which is statistically random? For passive sliders driven by various
      fluctuating surfaces, we show that the approach involves an indefinitely growing
      length scale which governs scaling properties. A simple model of sticky sliders
      suggests scaling forms for the time-dependent flatness and hyperflatness, both
      measures of intermittency and these are confirmed numerically for passive sliders
      driven by a Kardar-Parisi-Zhang surface. Aging properties are studied via a two
      time flatness. We predict and verify numerically that the time-dependent flatness
      is, remarkably, a nonmonotonic function of time with different scaling forms at
      short and long times. The scaling description remains valid when clustering is
      more diffuse as for passive sliders evolving through Edwards-Wilkinson driving or
      under antiadvection, although exponents and scaling functions differ
      substantially.

PMID- 29448380
TI  - Theoretical model of chirality-induced helical self-propulsion.
AB  - We recently reported the experimental realization of a chiral artificial
      microswimmer exhibiting helical self-propulsion [T. Yamamoto and M. Sano, Soft
      Matter 13, 3328 (2017)1744-683X10.1039/C7SM00337D]. In the experiment,
      cholesteric liquid crystal (CLC) droplets dispersed in surfactant solutions swam
      spontaneously, driven by the Marangoni flow, in helical paths whose handedness is
      determined by the chirality of the component molecules of CLC. To study the
      mechanism of the emergence of the helical self-propelled motion, we propose a
      phenomenological model of the self-propelled helical motion of the CLC droplets.
      Our model is constructed by symmetry argument in chiral systems, and it describes
      the dynamics of CLC droplets with coupled time-evolution equations in terms of a
      velocity, an angular velocity, and a tensor variable representing the symmetry of
      the helical director field of the droplet. We found that helical motions as well
      as other chiral motions appear in our model. By investigating bifurcation
      behaviors between each chiral motion, we found that the chiral coupling terms
      between the velocity and the angular velocity, the structural anisotropy of the
      CLC droplet, and the nonlinearity of model equations play a crucial role in the
      emergence of the helical motion of the CLC droplet.

PMID- 29448381
TI  - Wave failure at strong coupling in intracellular Ca^{2+} signaling system with
      clustered channels.
AB  - As an important intracellular signal, Ca^{2+} ions control diverse cellular
      functions. In this paper, we discuss the Ca^{2+} signaling with a two-dimensional
      model in which the inositol 1,4,5-trisphosphate (IP_{3}) receptor channels are
      distributed in clusters on the endoplasmic reticulum membrane. The wave failure
      at large Ca^{2+} diffusion coupling is discussed in detail in the model. We show
      that with varying model parameters the wave failure is a robust behavior with
      either deterministic or stochastic channel dynamics. We suggest that the wave
      failure should be a general behavior in inhomogeneous diffusing systems with
      clustered excitable regions and may occur in biological Ca^{2+} signaling
      systems.

PMID- 29448382
TI  - Relaxation dynamics of maximally clustered networks.
AB  - We study the relaxation dynamics of fully clustered networks (maximal number of
      triangles) to an unclustered state under two different edge dynamics-the double
      edge swap, corresponding to degree-preserving randomization of the configuration
      model, and single edge replacement, corresponding to full randomization of the
      Erdos-Renyi random graph. We derive expressions for the time evolution of the
      degree distribution, edge multiplicity distribution and clustering coefficient.
      We show that under both dynamics networks undergo a continuous phase transition
      in which a giant connected component is formed. We calculate the position of the
      phase transition analytically using the Erdos-Renyi phenomenology.

PMID- 29448383
TI  - Microscopic processes controlling the Herschel-Bulkley exponent.
AB  - The flow curve of various yield stress materials is singular as the strain rate
      vanishes and can be characterized by the so-called Herschel-Bulkley exponent
      n=1/beta. A mean-field approximation due to Hebraud and Lequeux (HL) assumes
      mechanical noise to be Gaussian and leads to beta=2 in rather good agreement with
      observations. Here we prove that the improved mean-field model where the
      mechanical noise has fat tails instead leads to beta=1 with logarithmic
      correction. This result supports that HL is not a suitable explanation for the
      value of beta, which is instead significantly affected by finite-dimensional
      effects. From considerations on elastoplastic models and on the limitation of
      speed at which avalanches of plasticity can propagate, we argue that beta=1+1/(d
      d_{f}), where d_{f} is the fractal dimension of avalanches and d the spatial
      dimension. Measurements of d_{f} then supports that beta~2.1 and beta~1.7 in two
      and three dimensions, respectively. We discuss theoretical arguments leading to
      approximations of beta in finite dimensions.

PMID- 29448384
TI  - Thermal convection in three-dimensional fractured porous media.
AB  - Thermal convection is numerically computed in three-dimensional (3D) fluid
      saturated isotropically fractured porous media. Fractures are randomly inserted
      as two-dimensional (2D) convex polygons. Flow is governed by Darcy's 2D and 3D
      laws in the fractures and in the porous medium, respectively; exchanges take
      place between these two structures. Results for unfractured porous media are in
      agreement with known theoretical predictions. The influence of parameters such as
      the fracture aperture (or fracture transmissivity) and the fracture density on
      the heat released by the whole system is studied for Rayleigh numbers up to 150
      in cubic boxes with closed-top conditions. Then, fractured media are compared to
      homogeneous porous media with the same macroscopic properties. Three major
      results could be derived from this study. The behavior of the system, in terms of
      heat release, is determined as a function of fracture density and fracture
      transmissivity. First, the increase in the output flux with fracture density is
      linear over the range of fracture density tested. Second, the increase in output
      flux as a function of fracture transmissivity shows the importance of
      percolation. Third, results show that the effective approach is not always valid,
      and that the mismatch between the full calculations and the effective medium
      approach depends on the fracture density in a crucial way.

PMID- 29448385
TI  - Anisotropic particles strengthen granular pillars under compression.
AB  - We probe the effects of particle shape on the global and local behavior of a two
      dimensional granular pillar, acting as a proxy for a disordered solid, under
      uniaxial compression. This geometry allows for direct measurement of global
      material response, as well as tracking of all individual particle trajectories.
      In general, drawing connections between local structure and local dynamics can be
      challenging in amorphous materials due to lower precision of atomic positions, so
      this study aims to elucidate such connections. We vary local interactions by
      using three different particle shapes: discrete circular grains (monomers), pairs
      of grains bonded together (dimers), and groups of three bonded in a triangle
      (trimers). We find that dimers substantially strengthen the pillar and the degree
      of this effect is determined by orientational order in the initial condition. In
      addition, while the three particle shapes form void regions at distinct rates, we
      find that anisotropies in the local amorphous structure remain robust through the
      definition of a metric that quantifies packing anisotropy. Finally, we highlight
      connections between local deformation rates and local structure.

PMID- 29448386
TI  - Theoretical analysis of the distribution of isolated particles in totally
      asymmetric exclusion processes: Application to mRNA translation rate estimation.
AB  - The Totally Asymmetric Exclusion Process (TASEP) is a classical stochastic model
      for describing the transport of interacting particles, such as ribosomes moving
      along the messenger ribonucleic acid (mRNA) during translation. Although this
      model has been widely studied in the past, the extent of collision between
      particles and the average distance between a particle to its nearest neighbor
      have not been quantified explicitly. We provide here a theoretical analysis of
      such quantities via the distribution of isolated particles. In the classical form
      of the model in which each particle occupies only a single site, we obtain an
      exact analytic solution using the matrix ansatz. We then employ a refined mean
      field approach to extend the analysis to a generalized TASEP with particles of an
      arbitrary size. Our theoretical study has direct applications in mRNA translation
      and the interpretation of experimental ribosome profiling data. In particular,
      our analysis of data from Saccharomyces cerevisiae suggests a potential bias
      against the detection of nearby ribosomes with a gap distance of less than
      approximately three codons, which leads to some ambiguity in estimating the
      initiation rate and protein production flux for a substantial fraction of genes.
      Despite such ambiguity, however, we demonstrate theoretically that the
      interference rate associated with collisions can be robustly estimated and show
      that approximately 1% of the translating ribosomes get obstructed.

PMID- 29448387
TI  - Pressure evolution and deformation of confined granular media during pneumatic
      fracturing.
AB  - By means of digital image correlation, we experimentally characterize the
      deformation of a dry granular medium confined inside a Hele-Shaw cell due to air
      injection at a constant overpressure high enough to deform it (from 50 to 250
      kPa). Air injection at these overpressures leads to the formation of so-called
      pneumatic fractures, i.e., channels empty of beads, and we discuss the typical
      deformations of the medium surrounding these structures. In addition we simulate
      the diffusion of the fluid overpressure into the medium, comparing it with the
      Laplacian solution over time and relating pressure gradients with corresponding
      granular displacements. In the compacting medium we show that the diffusing
      pressure field becomes similar to the Laplace solution on the order of a
      characteristic time given by the properties of the pore fluid, the granular
      medium, and the system size. However, before the diffusing pressure approaches
      the Laplace solution on the system scale, we find that it resembles the Laplacian
      field near the channels, with the highest pressure gradients on the most advanced
      channel tips and a screened pressure gradient behind them. We show that the
      granular displacements more or less always move in the direction against the
      local pressure gradients, and when comparing granular velocities with pressure
      gradients in the zone ahead of channels, we observe a Bingham type of rheology
      for the granular paste (the mix of air and beads), with an effective viscosity
      MU_{B} and displacement thresholds ?[over ?]P_{c} evolving during mobilization
      and compaction of the medium. Such a rheology, with disorder in the displacement
      thresholds, could be responsible for placing the pattern growth at moderate
      injection pressures in a universality class like the dielectric breakdown model
      with eta=2, where fractal dimensions are found between 1.5 and 1.6 for the
      patterns.

PMID- 29448388
TI  - Patterning of a cohesionless granular layer under pure shear.
AB  - The response of a thin layer of granular material to an external pure shear
      imposed at its base is investigated. The experiments show that, even for
      noncohesive materials, the resulting deformation of the material is
      inhomogeneous. Indeed, a novel smooth pattern, consisting of a periodic
      modulation of the shear deformation of the free surface, is revealed by an image
      correlation technique. These observations are in contrast with the previous
      observation of the fracture pattern in cohesive granular materials subjected to
      stretching. For cohesive materials, the instability is due to the weakening of
      the material which results from the rupture of capillary bridges that bond the
      grains to one another. For noncohesive materials, the rupture of the capillary
      bridges cannot be invoked anymore. We show that the instability results from the
      decrease of friction on shearing. PACS: 89.75.Kd: Pattern formation in complex
      systems; 83.60.Uv: Rheology: fracture; 45.70.Qj: Pattern formation in granular
      matter.

PMID- 29448389
TI  - Development of an efficient gas kinetic scheme for simulation of two-dimensional
      incompressible thermal flows.
AB  - In this work, an efficient gas kinetic scheme is presented for simulation of two
      dimensional incompressible thermal flows. In the scheme, the macroscopic
      governing equations for mass, momentum, and energy conservation are discretized
      by the finite volume method and the numerical fluxes at the cell interface are
      reconstructed by the local solution of the Boltzmann equation. To compute these
      fluxes, two distribution functions are involved. One is the circular function,
      which is used to calculate the numerical fluxes of mass and momentum equations.
      Due to the incompressible limit, the circle at the cell interface can be
      approximately considered to be symmetric so that the expressions for the
      conservative variables and numerical fluxes at the cell interface can be given
      explicitly and concisely. Another one is the D2Q4 model, which is utilized to
      compute the numerical flux of the energy equation. By following the process for
      derivation of numerical fluxes of mass and momentum equations, the numerical flux
      of the energy equation can also be given explicitly. The accuracy, efficiency,
      and stability of the present scheme are validated by simulating several thermal
      flow problems. Numerical results showed that the present scheme can provide
      accurate numerical results for incompressible thermal flows at a wide range of
      Rayleigh numbers with less computational cost than that needed by the thermal
      lattice Boltzmann flux solver (TLBFS), which has been proven to be more efficient
      than the thermal lattice Boltzmann method (TLBM).

PMID- 29448390
TI  - Kullback-Leibler divergence measure of intermittency: Application to turbulence.
AB  - For generic systems exhibiting power law behaviors, and hence multiscale
      dependencies, we propose a simple tool to analyze multifractality and
      intermittency, after noticing that these concepts are directly related to the
      deformation of a probability density function from Gaussian at large scales to
      non-Gaussian at smaller scales. Our framework is based on information theory and
      uses Shannon entropy and Kullback-Leibler divergence. We provide an extensive
      application to three-dimensional fully developed turbulence, seen here as a
      paradigmatic complex system where intermittency was historically defined and the
      concepts of scale invariance and multifractality were extensively studied and
      benchmarked. We compute our quantity on experimental Eulerian velocity
      measurements, as well as on synthetic processes and phenomenological models of
      fluid turbulence. Our approach is very general and does not require any
      underlying model of the system, although it can probe the relevance of such a
      model.

PMID- 29448391
TI  - Relationship between the mechanisms of gamma rhythm generation and the magnitude
      of the macroscopic phase response function in a population of excitatory and
      inhibitory modified quadratic integrate-and-fire neurons.
AB  - Gamma oscillations are thought to play an important role in brain function.
      Interneuron gamma (ING) and pyramidal interneuron gamma (PING) mechanisms have
      been proposed as generation mechanisms for these oscillations. However, the
      relation between the generation mechanisms and the dynamical properties of the
      gamma oscillation are still unclear. Among the dynamical properties of the gamma
      oscillation, the phase response function (PRF) is important because it encodes
      the response of the oscillation to inputs. Recently, the PRF for an inhibitory
      population of modified theta neurons that generate an ING rhythm was computed by
      the adjoint method applied to the associated Fokker-Planck equation (FPE) for the
      model. The modified theta model incorporates conductance-based synapses as well
      as the voltage and current dynamics. Here, we extended this previous work by
      creating an excitatory-inhibitory (E-I) network using the modified theta model
      and described the population dynamics with the corresponding FPE. We conducted a
      bifurcation analysis of the FPE to find parameter regions which generate gamma
      oscillations. In order to label the oscillatory parameter regions by their
      generation mechanisms, we defined ING- and PING-type gamma oscillation in a
      mathematically plausible way based on the driver of the inhibitory population. We
      labeled the oscillatory parameter regions by these generation mechanisms and
      derived PRFs via the adjoint method on the FPE in order to investigate the
      differences in the responses of each type of oscillation to inputs. PRFs for PING
      and ING mechanisms are derived and compared. We found the amplitude of the PRF
      for the excitatory population is larger in the PING case than in the ING case.
      Finally, the E-I population of the modified theta neuron enabled us to analyze
      the PRFs of PING-type gamma oscillation and the entrainment ability of E and I
      populations. We found a parameter region in which PRFs of E and I are both purely
      positive in the case of PING oscillations. The different entrainment abilities of
      E and I stimulation as governed by the respective PRFs was compared to direct
      simulations of finite populations of model neurons. We find that it is easier to
      entrain the gamma rhythm by stimulating the inhibitory population than by
      stimulating the excitatory population as has been found experimentally.

PMID- 29448392
TI  - Ordering transitions of weakly anisotropic hard rods in narrow slitlike pores.
AB  - The effect of strong confinement on the positional and orientational ordering is
      examined in a system of hard rectangular rods with length L and diameter D (L>D)
      using the Parsons-Lee modification of the second virial density-functional
      theory. The rods are nonmesogenic (L/D<3) and confined between two parallel hard
      walls, where the width of the pore (H) is chosen in such a way that both planar
      (particle's long axis parallel to the walls) and homeotropic (particle's long
      axis perpendicular to the walls) orderings are possible and a maximum of two
      layers is allowed to form in the pore. In the extreme confinement limit of H<=2D,
      where only one-layer structures appear, we observe a structural transition from a
      planar to a homeotropic fluid layer with increasing density, which becomes
      sharper as L->H. In wider pores (2D<H<3D) planar order with two layers,
      homeotropic order, and even combined bilayer structures (one layer is
      homeotropic, while the other is planar) can be stabilized at high densities.
      Moreover, first-order phase transitions can be seen between different structures.
      One of them emerges between a monolayer and a bilayer with planar orders at
      relatively low packing fractions.

PMID- 29448393
TI  - Localized instabilities and spinodal decomposition in driven systems in the
      presence of elasticity.
AB  - We study numerically and analytically the instabilities associated with phase
      separation in a solid layer on which an external material flux is imposed. The
      first instability is localized within a boundary layer at the exposed free
      surface by a process akin to spinodal decomposition. In the limiting static case,
      when there is no material flux, the coherent spinodal decomposition is recovered.
      In the present problem, stability analysis of the time-dependent and nonuniform
      base states as well as numerical simulations of the full governing equations are
      used to establish the dependence of the wavelength and onset of the instability
      on parameter settings and its transient nature as the patterns eventually coarsen
      into a flat moving front. The second instability is related to the Mullins
      Sekerka instability in the presence of elasticity and arises at the moving front
      between the two phases when the flux is reversed. Stability analyses of the full
      model and the corresponding sharp-interface model are carried out and compared.
      Our results demonstrate how interface and bulk instabilities can be analyzed
      within the same framework which allows us to identify and distinguish each of
      them clearly. The relevance for a detailed understanding of both instabilities
      and their interconnections in a realistic setting is demonstrated for a system of
      equations modeling the lithiation and delithiation processes within the context
      of lithium ion batteries.

PMID- 29448394
TI  - Attenuation of slow (10-40 eV) electrons in soft nanoparticles: Size matters in
      argon clusters.
AB  - Electron attenuation due to inelastic and elastic scattering in condensed media
      can often be described in terms of the effective attenuation length (EAL) of the
      electron. The EAL is thus an important parameter for describing electron
      transport processes as exemplified by dissipation of energy following radiolysis.
      Focusing on electrons at low electron kinetic energies (10-40 eV) in condensed
      argon, we determine EAL from x-ray photoelectron spectra of argon nanoparticles
      and compare to values obtained from valence ionization in thin argon films as
      well as from gas-phase electron-scattering data. EAL determined from argon
      clusters shows variation with cluster size. Moreover, the values are
      significantly lower than those obtained in valence-ionization studies and from
      scattering data. Our results corroborate recent x-ray photoelectron spectroscopy
      based determination of EALs of water showing large differences to the EALs
      determined by other methods in amorphous ice at low kinetic energies of the
      photoelectron [Y.-I. Suzuki, K. Nishizawa, N. Kurahashi, and T. Suzuki, Phys.
      Rev. E 90, 010302 (2014)PLEEE81539-375510.1103/PhysRevE.90.010302], underlining
      that care must be taken when using EAL values from other sources for core-level
      electrons.

PMID- 29448395
TI  - Disordered multihyperuniformity derived from binary plasmas.
AB  - Disordered multihyperuniform many-particle systems are exotic amorphous states
      that allow exquisite color sensing capabilities due to their anomalous
      suppression of density fluctuations for distinct subsets of particles, as
      recently evidenced in photoreceptor mosaics in avian retina. Motivated by this
      biological finding, we present a statistical-mechanical model that rigorously
      achieves disordered multihyperuniform many-body systems by tuning interactions in
      binary mixtures of nonadditive hard-disk plasmas. We demonstrate that
      multihyperuniformity competes with phase separation and stabilizes a clustered
      phase. Our work provides a systematic means to generate disordered
      multihyperuniform solids, and hence lays the groundwork to explore their
      potentially unique photonic, phononic, electronic, and transport properties.

PMID- 29448396
TI  - Measuring the equations of state in a relaxed magnetohydrodynamic plasma.
AB  - We report measurements of the equations of state of a fully relaxed
      magnetohydrodynamic (MHD) laboratory plasma. Parcels of magnetized plasma, called
      Taylor states, are formed in a coaxial magnetized plasma gun, and are allowed to
      relax and drift into a closed flux conserving volume. Density, ion temperature,
      and magnetic field are measured as a function of time as the Taylor states
      compress and heat. The theoretically predicted MHD and double adiabatic equations
      of state are compared to experimental measurements. We find that the MHD equation
      of state is inconsistent with our data.

PMID- 29448397
TI  - Critical phenomena in quasi-two-dimensional vibrated granular systems.
AB  - The critical phenomena associated to the liquid-to-solid transition of quasi-two
      dimensional vibrated granular systems is studied using molecular dynamics
      simulations of the inelastic hard sphere model. The critical properties are
      associated to the fourfold bond-orientational order parameter chi_{4}, which
      measures the level of square crystallization of the system. Previous experimental
      results have shown that the transition of chi_{4}, when varying the vibration
      amplitude, can be either discontinuous or continuous, for two different values of
      the height of the box. Exploring the amplitude-height phase space, a transition
      line is found, which can be either discontinuous or continuous, merging at a
      tricritical point and the continuous branch ends in an upper critical point. In
      the continuous transition branch, the critical properties are studied. The
      exponent associated to the amplitude of the order parameter is beta=1/2, for
      various system sizes, in complete agreement with the experimental results.
      However, the fluctuations of chi_{4} do not show any critical behavior, probably
      due to crossover effects by the close presence of the tricritical point. Finally,
      in quasi-one-dimensional systems, the transition is only discontinuous, limited
      by one critical point, indicating that two is the lower dimension for having a
      tricritical point.

PMID- 29448398
TI  - Editorial: A Tale of Two Anniversaries: 125 Years of the Physical Review and 25
      Years of Physical Review E.

PMID- 29448399
TI  - Probabilistic low-rank factorization accelerates tensor network simulations of
      critical quantum many-body ground states.
AB  - We provide evidence that randomized low-rank factorization is a powerful tool for
      the determination of the ground-state properties of low-dimensional lattice
      Hamiltonians through tensor network techniques. In particular, we show that
      randomized matrix factorization outperforms truncated singular value
      decomposition based on state-of-the-art deterministic routines in time-evolving
      block decimation (TEBD)- and density matrix renormalization group (DMRG)-style
      simulations, even when the system under study gets close to a phase transition:
      We report linear speedups in the bond or local dimension of up to 24 times in
      quasi-two-dimensional cylindrical systems.

PMID- 29448400
TI  - Out-of-time-order fluctuation-dissipation theorem.
AB  - We prove a generalized fluctuation-dissipation theorem for a certain class of out
      of-time-ordered correlators (OTOCs) with a modified statistical average, which we
      call bipartite OTOCs, for general quantum systems in thermal equilibrium. The
      difference between the bipartite and physical OTOCs defined by the usual
      statistical average is quantified by a measure of quantum fluctuations known as
      the Wigner-Yanase skew information. Within this difference, the theorem describes
      a universal relation between chaotic behavior in quantum systems and a nonlinear
      response function that involves a time-reversed process. We show that the theorem
      can be generalized to higher-order n-partite OTOCs as well as in the form of
      generalized covariance.

PMID- 29448401
TI  - Publisher's Note: Linear relaxation in large two-dimensional Ising models [Phys.
      Rev. E 93, 022113 (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.93.022113.

PMID- 29448402
TI  - Nonreciprocity in the dynamics of coupled oscillators with nonlinearity,
      asymmetry, and scale hierarchy.
AB  - In linear time-invariant dynamical and acoustical systems, reciprocity holds by
      the Onsager-Casimir principle of microscopic reversibility, and this can be
      broken only by odd external biases, nonlinearities, or time-dependent properties.
      A concept is proposed in this work for breaking dynamic reciprocity based on
      irreversible nonlinear energy transfers from large to small scales in a system
      with nonlinear hierarchical internal structure, asymmetry, and intentional strong
      stiffness nonlinearity. The resulting nonreciprocal large-to-small scale energy
      transfers mimic analogous nonlinear energy transfer cascades that occur in nature
      (e.g., in turbulent flows), and are caused by the strong frequency-energy
      dependence of the essentially nonlinear small-scale components of the system
      considered. The theoretical part of this work is mainly based on action-angle
      transformations, followed by direct numerical simulations of the resulting system
      of nonlinear coupled oscillators. The experimental part considers a system with
      two scales-a linear large-scale oscillator coupled to a small scale by a
      nonlinear spring-and validates the theoretical findings demonstrating
      nonreciprocal large-to-small scale energy transfer. The proposed study promotes a
      paradigm for designing nonreciprocal acoustic materials harnessing strong
      nonlinearity, which in a future application will be implemented in designing
      lattices incorporating nonlinear hierarchical internal structures, asymmetry, and
      scale mixing.

PMID- 29448403
TI  - Entrance and escape dynamics for the typical set.
AB  - According to the asymptotic equipartition property, sufficiently long sequences
      of random variables converge to a set that is typical. While the size and
      probability of this set are central to information theory and statistical
      mechanics, they can often only be estimated accurately in the asymptotic limit
      due to the exponential growth in possible sequences. Here we derive a time
      inhomogeneous dynamics that constructs the properties of the typical set for all
      finite length sequences of independent and identically distributed random
      variables. These dynamics link the finite properties of the typical set to
      asymptotic results and allow the typical set to be applied to small and transient
      systems. The main result is a geometric mapping-the triangle map-relating
      sequences of random variables of length n to those of length n+1. We show that
      the number of points in this map needed to quantify the properties of the typical
      set grows linearly with sequence length, despite the exponential growth in the
      number of typical sequences. We illustrate the framework for the Bernoulli
      process and the Schlogl model for autocatalytic chemical reactions and
      demonstrate both the convergence to asymptotic limits and the ability to
      reproduce exact calculations.

PMID- 29448404
TI  - Lattice Wigner equation.
AB  - We present a numerical scheme to solve the Wigner equation, based on a lattice
      discretization of momentum space. The moments of the Wigner function are
      recovered exactly, up to the desired order given by the number of discrete
      momenta retained in the discretization, which also determines the accuracy of the
      method. The Wigner equation is equipped with an additional collision operator,
      designed in such a way as to ensure numerical stability without affecting the
      evolution of the relevant moments of the Wigner function. The lattice Wigner
      scheme is validated for the case of quantum harmonic and anharmonic potentials,
      showing good agreement with theoretical results. It is further applied to the
      study of the transport properties of one- and two-dimensional open quantum
      systems with potential barriers. Finally, the computational viability of the
      scheme for the case of three-dimensional open systems is also illustrated.

PMID- 29448405
TI  - Generalized thermalization for integrable system under quantum quench.
AB  - We investigate equilibration and generalized thermalization of the quantum
      Harmonic chain under local quantum quench. The quench action we consider is
      connecting two disjoint harmonic chains of different sizes and the system jumps
      between two integrable settings. We verify the validity of the generalized Gibbs
      ensemble description for this infinite-dimensional Hilbert space system and also
      identify equilibration between the subsystems as in classical systems. Using
      Bogoliubov transformations, we show that the eigenstates of the system prior to
      the quench evolve toward the Gibbs Generalized Ensemble description. Eigenstates
      that are more delocalized (in the sense of inverse participation ratio) prior to
      the quench, tend to equilibrate more rapidly. Further, through the phase space
      properties of a generalized Gibbs ensemble and the strength of stimulated
      emission, we identify the necessary criterion on the initial states for such
      relaxation at late times and also find out the states that would potentially not
      be described by the generalized Gibbs ensemble description.

PMID- 29448406
TI  - Hypostatic jammed packings of frictionless nonspherical particles.
AB  - We perform computational studies of static packings of a variety of nonspherical
      particles including circulo-lines, circulo-polygons, ellipses, asymmetric dimers,
      dumbbells, and others to determine which shapes form packings with fewer contacts
      than degrees of freedom (hypostatic packings) and which have equal numbers of
      contacts and degrees of freedom (isostatic packings), and to understand why
      hypostatic packings of nonspherical particles can be mechanically stable despite
      having fewer contacts than that predicted from naive constraint counting. To
      generate highly accurate force- and torque-balanced packings of circulo-lines and
      cir-polygons, we developed an interparticle potential that gives continuous
      forces and torques as a function of the particle coordinates. We show that the
      packing fraction and coordination number at jamming onset obey a masterlike form
      for all of the nonspherical particle packings we studied when plotted versus the
      particle asphericity A, which is proportional to the ratio of the squared
      perimeter to the area of the particle. Further, the eigenvalue spectra of the
      dynamical matrix for packings of different particle shapes collapse when plotted
      at the same A. For hypostatic packings of nonspherical particles, we verify that
      the number of "quartic" modes along which the potential energy increases as the
      fourth power of the perturbation amplitude matches the number of missing contacts
      relative to the isostatic value. We show that the fourth derivatives of the total
      potential energy in the directions of the quartic modes remain nonzero as the
      pressure of the packings is decreased to zero. In addition, we calculate the
      principal curvatures of the inequality constraints for each contact in circulo
      line packings and identify specific types of contacts with inequality constraints
      that possess convex curvature. These contacts can constrain multiple degrees of
      freedom and allow hypostatic packings of nonspherical particles to be
      mechanically stable.

PMID- 29448407
TI  - Matrix product solution of a left-permeable two-species asymmetric exclusion
      process.
AB  - We study a two-species partially asymmetric exclusion process where the left
      boundary is permeable for the "slower" species but the right boundary is not. We
      find a matrix product solution for the stationary state and the exact stationary
      phase diagram for the densities and currents. By calculating the density of each
      species at the boundaries, we find further structure in the stationary phases. In
      particular, we find that the slower species can reach and accumulate at the far
      boundary, even in phases where the bulk density of these particles approaches
      zero.

PMID- 29448408
TI  - Energy dissipation in a friction-controlled slide of a body excited by random
      motions of the foundation.
AB  - We study a friction-controlled slide of a body excited by random motions of the
      foundation it is placed on. Specifically, we are interested in such quantities as
      displacement, traveled distance, and energy loss due to friction. We assume that
      the random excitation is switched off at some time (possibly infinite) and show
      that the problem can be treated in an analytic, explicit, manner. Particularly,
      we derive formulas for the moments of the displacement and distance, and also for
      the average energy loss. To accomplish that we use the Pugachev-Sveshnikov
      equation for the characteristic function of a continuous random process given by
      a system of SDEs. This equation is solved by reduction to a parametric Riemann
      boundary value problem of complex analysis.

PMID- 29448409
TI  - Ultrasonic measurements of the bulk flow field in foams.
AB  - The flow field of moving foams is relevant for basic research and for the
      optimization of industrial processes such as froth flotation. However, no
      adequate measurement technique exists for the local velocity distribution inside
      the foam bulk. We have investigated the ultrasound Doppler velocimetry (UDV),
      providing the first two-dimensional, non-invasive velocity measurement technique
      with an adequate spatial (10mm) and temporal resolution (2.5Hz) that is
      applicable to medium scale foam flows. The measurement object is dry aqueous foam
      flowing upward in a rectangular channel. An array of ultrasound transducers is
      mounted within the channel, sending pulses along the main flow axis, and
      receiving echoes from the foam bulk. This results in a temporally and spatially
      resolved, planar velocity field up to a measurement depth of 200mm, which is
      approximately one order of magnitude larger than those of optical techniques. A
      comparison with optical reference measurements of the surface velocity of the
      foam allows to validate the UDV results. At 2.5Hz frame rate an uncertainty below
      15 percent and an axial spatial resolution better than 10mm is found. Therefore,
      UDV is a suitable tool for monitoring of industrial processes as well as the
      scientific investigation of three-dimensional foam flows on medium scales.

PMID- 29448410
TI  - Multispecies exclusion process with fusion and fission of rods: A model inspired
      by intraflagellar transport.
AB  - We introduce a multispecies exclusion model where length-conserving probabilistic
      fusion and fission of the hard rods are allowed. Although all rods enter the
      system with the same initial length l=1, their length can keep changing, because
      of fusion and fission, as they move in a step-by-step manner towards the exit.
      Two neighboring hard rods of lengths l_{1} and l_{2} can fuse into a single rod
      of longer length l=l_{1}+l_{2} provided l<=N. Similarly, length-conserving
      fission of a rod of length l^{'}<=N results in two shorter daughter rods. Based
      on the extremum current hypothesis, we plot the phase diagram of the model under
      open boundary conditions utilizing the results derived for the same model under
      periodic boundary condition using mean-field approximation. The density profile
      and the flux profile of rods are in excellent agreement with computer
      simulations. Although the fusion and fission of the rods are motivated by similar
      phenomena observed in intraflagellar transport (IFT) in eukaryotic flagella, this
      exclusion model is too simple to account for the quantitative experimental data
      for any specific organism. Nevertheless, the concepts of "flux profile" and
      "transition zone" that emerge from the interplay of fusion and fission in this
      model are likely to have important implications for IFT and for other similar
      transport phenomena in long cell protrusions.

PMID- 29448411
TI  - Kinetic theory for strongly coupled Coulomb systems.
AB  - The calculation of dynamical properties for matter under extreme conditions is a
      challenging task. The popular Kubo-Greenwood model exploits elements from
      equilibrium density-functional theory (DFT) that allow a detailed treatment of
      electron correlations, but its origin is largely phenomenological; traditional
      kinetic theories have a more secure foundation but are limited to weak ion
      electron interactions. The objective here is to show how a combination of the two
      evolves naturally from the short-time limit for the generator of the effective
      single-electron dynamics governing time correlation functions without such
      limitations. This provides a theoretical context for the current DFT-related
      approach, the Kubo-Greenwood model, while showing the nature of its corrections.
      The method is to calculate the short-time dynamics in the single-electron
      subspace for a given configuration of the ions. This differs from the usual
      kinetic theory approach in which an average over the ions is performed as well.
      In this way the effective ion-electron interaction includes strong Coulomb
      coupling and is shown to be determined from DFT. The correlation functions have
      the form of the random-phase approximation for an inhomogeneous system but with
      renormalized ion-electron and electron-electron potentials. The dynamic structure
      function, density response function, and electrical conductivity are calculated
      as examples. The static local field corrections in the dielectric function are
      identified in this way. The current analysis is limited to semiclassical
      electrons (quantum statistical potentials), so important quantum conditions are
      excluded. However, a quantization of the kinetic theory is identified for broader
      application while awaiting its detailed derivation.

PMID- 29448412
TI  - Subordinated stochastic processes with aged operational time.
AB  - In this paper, subordinated stochastic processes are considered, where the
      renewal process acting as the operational time. It is assumed that the
      observation of the process begins at a certain time after the start of the
      renewal process. A recurrence formula was derived for calculating the multipoint
      probability density functions of the aged renewal process. Two-point correlation
      functions for certain subordinated stochastic processes, particularly for the
      generalized Ornstein-Uhlenbeck process, were calculated. A model of relaxation in
      a disordered medium with traps and obstacles is proposed.

PMID- 29448413
TI  - Electrohydrodynamic instability of premixed flames under manipulations of dc
      electric fields.
AB  - We report an electrohydrodynamic instability in a premixed stagnation flame under
      manipulations of a dc electric field. This instability occurs when the electric
      field strength is at a certain value below the breakdown threshold, which is 0.75
      kV/cm in the experimental setup. Above this value the flame front suddenly
      transits from a substrate-stabilized near-flat shape to a nozzle-stabilized
      conical surface, accompanied by a jump in the electric current through the flame
      field. At the transition moment, the flame spontaneously propagates upstream to
      the nozzle while the flow velocity at the upstream of the flame front decreases
      to zero, as revealed by high-speed photographs and PIV measurements. These
      phenomena indicate a transient balance between the fluid inertia and the electric
      body force around the instability threshold. A quantitative model suggests that
      the flame instability can be explained by a positive feedback loop, where the
      electric field applies a nonuniform electric body force, pulling the flame front
      upstream, and the pulled flame front in turn enhances the local electric body
      force. The electrohydrodynamic instability occurs when the electric pulling is
      strong enough and both the growth rates and the magnitudes of the electric body
      force on flame exceed those of the fluid dynamic pressure.

PMID- 29448414
TI  - Higher-order corrections to the effective potential close to the jamming
      transition in the perceptron model.
AB  - In view of the results achieved in a previously related work [A. Altieri, S.
      Franz, and G. Parisi, J. Stat. Mech. (2016) 093301]10.1088/1742
      5468/2016/09/093301, regarding a Plefka-like expansion of the free energy up to
      the second order in the perceptron model, we improve the computation here
      focusing on the role of third-order corrections. The perceptron model is a simple
      example of constraint satisfaction problem, falling in the same universality
      class as hard spheres near jamming and hence allowing us to get exact results in
      high dimensions for more complex settings. Our method enables to define an
      effective potential (or Thouless-Anderson-Palmer free energy), namely a coarse
      grained functional, which depends on the generalized forces and the effective
      gaps between particles. The analysis of the third-order corrections to the
      effective potential reveals that, albeit irrelevant in a mean-field framework in
      the thermodynamic limit, they might instead play a fundamental role in
      considering finite-size effects. We also study the typical behavior of
      generalized forces and we show that two kinds of corrections can occur. The first
      contribution arises since the system is analyzed at a finite distance from
      jamming, while the second one is due to finite-size corrections. We nevertheless
      show that third-order corrections in the perturbative expansion vanish in the
      jamming limit both for the potential and the generalized forces, in agreement
      with the isostaticity argument proposed by Wyart and coworkers. Finally, we
      analyze the relevant scaling solutions emerging close to the jamming line, which
      define a crossover regime connecting the control parameters of the model to an
      effective temperature.

PMID- 29448415
TI  - Drive-induced delocalization in the Aubry-Andre model.
AB  - Motivated by the recent experiment by Bordia et al. [Nat. Phys. 13, 460
      (2017)NPAHAX1745-247310.1038/nphys4020], we study the single particle
      delocalization phenomena of the Aubry-Andre (AA) model subjected to periodic
      drives. In two distinct cases we construct an equivalent classical description to
      illustrate that the drive-induced delocalization phenomena stems from an
      instability and the onset of chaos in the underlying dynamics. In the first case
      we analyze the delocalization and the thermalization in a time modulated AA
      potential with respect to driving frequency and demonstrate that there exists a
      threshold value of the amplitude of the drive. In the next example, we show that
      the periodic modulation of the phase of the hopping amplitude induced by a gauge
      field leads to an unusual effect on delocalization with a nonmonotonic dependence
      on the driving frequency. Within a window of such a driving frequency a
      delocalized Floquet band with a mobility edge appears, exhibiting multifractality
      in the spectrum as well as in the Floquet eigenfunctions. Finally, we explore the
      effect of interaction and discuss how the results of the present analysis can be
      tested experimentally.

PMID- 29448416
TI  - Obtaining amplitude-modulated bursting by multiple-frequency slow parametric
      modulation.
AB  - Amplitude-modulated bursting (AMB), characterized by oscillations appearing in
      the envelope of the active phase of bursting, is a novel class of bursting
      rhythms reported recently. The present paper aims to report a simple and
      effective method, i.e., the multiple-frequency slow parametric modulation (MFSPM)
      method, for obtaining such a bursting pattern. We show that the MFSPM can be well
      controlled so that it may exhibit multiple continuous ups and downs in the active
      area. Then, the amplitude of the traced active state alternates between increases
      and decreases accordingly, which leads to oscillations in the envelope of the
      active phase, and AMB is thus created. Based on this, the route to AMB by the
      MFSPM is presented. The validity of the approach is demonstrated by several
      examples. The proposed approach does not depend on specific systems or
      bifurcations and thus is a general method.

PMID- 29448417
TI  - Magneto-optic dynamics in a ferromagnetic nematic liquid crystal.
AB  - We investigate dynamic magneto-optic effects in a ferromagnetic nematic liquid
      crystal experimentally and theoretically. Experimentally we measure the
      magnetization and the phase difference of the transmitted light when an external
      magnetic field is applied. As a model we study the coupled dynamics of the
      magnetization, M, and the director field, n, associated with the liquid
      crystalline orientational order. We demonstrate that the experimentally studied
      macroscopic dynamic behavior reveals the importance of a dynamic cross-coupling
      between M and n. The experimental data are used to extract the value of the
      dissipative cross-coupling coefficient. We also make concrete predictions about
      how reversible cross-coupling terms between the magnetization and the director
      could be detected experimentally by measurements of the transmitted light
      intensity as well as by analyzing the azimuthal angle of the magnetization and
      the director out of the plane spanned by the anchoring axis and the external
      magnetic field. We derive the eigenmodes of the coupled system and study their
      relaxation rates. We show that in the usual experimental setup used for measuring
      the relaxation rates of the splay-bend or twist-bend eigenmodes of a nematic
      liquid crystal one expects for a ferromagnetic nematic liquid crystal a mixture
      of at least two eigenmodes.

PMID- 29448418
TI  - Memory effects in active particles with exponentially correlated propulsion.
AB  - The Ornstein-Uhlenbeck particle (OUP) model imagines a microscopic swimmer
      propelled by an active force which is correlated with itself on a finite time
      scale. Here we investigate the influence of external potentials on an ideal
      suspension of OUPs, in both one and two spatial dimensions, with particular
      attention paid to the pressure exerted on "confining walls." We employ a
      mathematical connection between the local density of OUPs and the statistics of
      their propulsion force to demonstrate the existence of an equation of state in
      one dimension. In higher dimensions we show that active particles generate a
      nonconservative force field in the surrounding medium. A simplified far-from
      equilibrium model is proposed to account for OUP behavior in the vicinity of
      potentials. Building on this, we interpret simulations of OUPs in more
      complicated situations involving asymmetrical and spatially curved potentials,
      and characterize the resulting inhomogeneous stresses in terms of competing
      active length scales.

PMID- 29448419
TI  - General relations between the power, efficiency, and dissipation for the
      irreversible heat engines in the nonlinear response regime.
AB  - We derive the general relations between the maximum power, maximum efficiency,
      and minimum dissipation for the irreversible heat engine in a nonlinear response
      regime. In this context, we use the minimally nonlinear irreversible model and
      obtain the lower and upper bounds of the above relations for the asymmetric
      dissipation limits. These relations can be simplified further when the system
      possesses the time-reversal symmetry or antisymmetry. We find that our results
      are the generalization of various such relations obtained earlier for different
      heat engines.

PMID- 29448420
TI  - Low-noise phase of a two-dimensional active nematic system.
AB  - We consider a collection of self-driven apolar particles on a substrate that
      organize into an active nematic phase at sufficiently high density or low noise.
      Using the dynamical renormalization group, we systematically study the two
      dimensional fluctuating ordered phase in a coarse-grained hydrodynamic
      description involving both the nematic director and the conserved density field.
      In the presence of noise, we show that the system always displays only quasi-long
      ranged orientational order beyond a crossover scale. A careful analysis of the
      nonlinearities permitted by symmetry reveals that activity is dangerously
      irrelevant over the linearized description, allowing giant number fluctuations to
      persist although now with strong finite-size effects and a nonuniversal scaling
      exponent. Nonlinear effects from the active currents lead to power-law
      correlations in the density field, thereby preventing macroscopic phase
      separation in the thermodynamic limit.

PMID- 29448421
TI  - Cross-diffusion-induced subharmonic spatial resonances in a predator-prey system.
AB  - In this paper we investigate the complex dynamics originated by a cross-diffusion
      induced subharmonic destabilization of the fundamental subcritical Turing mode in
      a predator-prey reaction-diffusion system. The model we consider consists of a
      two-species Lotka-Volterra system with linear diffusion and a nonlinear cross
      diffusion term in the predator equation. The taxis term in the search strategy of
      the predator is responsible for the onset of complex dynamics. In fact, our model
      does not exhibit any Hopf or wave instability, and on the basis of the linear
      analysis one should only expect stationary patterns; nevertheless, the presence
      of the nonlinear cross-diffusion term is able to induce a secondary instability:
      due to a subharmonic spatial resonance, the stationary primary branch bifurcates
      to an out-of-phase oscillating solution. Noticeably, the strong resonance between
      the harmonic and the subharmonic is able to generate the oscillating pattern
      albeit the subharmonic is below criticality. We show that, as the control
      parameter is varied, the oscillating solution (subT mode) can undergo a sequence
      of secondary instabilities, generating a transition toward chaotic dynamics.
      Finally, we investigate the emergence of subT-mode solutions on two-dimensional
      domains: when the fundamental mode describes a square pattern, subharmonic
      resonance originates oscillating square patterns. In the case of subcritical
      Turing hexagon solutions, the internal interactions with a subharmonic mode are
      able to generate the so-called "twinkling-eyes" pattern.

PMID- 29448422
TI  - Solitons as candidates for energy carriers in Fermi-Pasta-Ulam lattices.
AB  - Currently, effective phonons (renormalized or interacting phonons) rather than
      solitary waves (for short, solitons) are regarded as the energy carriers in
      nonlinear lattices. In this work, by using the approximate soliton solutions of
      the corresponding equations of motion and adopting the Boltzmann distribution for
      these solitons, the average velocities of solitons are obtained and are compared
      with the sound velocities of energy transfer. Excellent agreements with the
      numerical results and the predictions of other existing theories are shown in
      both the symmetric Fermi-Pasta-Ulam-beta lattices and the asymmetric Fermi-Pasta
      Ulam-alphabeta lattices. These clearly indicate that solitons are suitable
      candidates for energy carriers in Fermi-Pasta-Ulam lattices. In addition, the
      root-mean-square velocity of solitons can be obtained from the effective phonons
      theory.

PMID- 29448423
TI  - Analytic expressions for electron-ion temperature equilibration rates from the
      Lenard-Balescu equation.
AB  - In this work, we elucidate the mathematical structure of the integral that arises
      when computing the electron-ion temperature equilibration time for a homogeneous
      weakly coupled plasma from the Lenard-Balescu equation. With some minor
      approximations, we derive an analytic formula, requiring no input Coulomb
      logarithm, for the equilibration rate that is valid for moderate electron-ion
      temperature ratios and arbitrary electron degeneracy. For large temperature
      ratios, we derive the necessary correction to account for the coupled-mode
      effect, which can be evaluated very efficiently using ordinary Gaussian
      quadrature.

PMID- 29448424
TI  - Multiplex recurrence networks.
AB  - We have introduced a multiplex recurrence network approach by combining
      recurrence networks with the multiplex network approach in order to investigate
      multivariate time series. The potential use of this approach is demonstrated on
      coupled map lattices and a typical example from palaeobotany research. In both
      examples, topological changes in the multiplex recurrence networks allow for the
      detection of regime changes in their dynamics. The method goes beyond classical
      interpretation of pollen records by considering the vegetation as a whole and
      using the intrinsic similarity in the dynamics of the different regional
      vegetation elements. We find that the different vegetation types behave more
      similarly when one environmental factor acts as the dominant driving force.

PMID- 29448425
TI  - Publisher's Note: Stochastic efficiency of an isothermal work-to-work converter
      engine [Phys. Rev. E 96, 042130 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.96.042130.

PMID- 29448426
TI  - Gross domestic product growth rates as confined Levy flights: Towards a unifying
      theory of economic growth rate fluctuations.
AB  - A model that combines economic growth rate fluctuations at the microscopic and
      macroscopic levels is presented. At the microscopic level, firms are growing at
      different rates while also being exposed to idiosyncratic shocks at the firm and
      sector levels. We describe such fluctuations as independent Levy-stable
      fluctuations, varying over multiple orders of magnitude. These fluctuations are
      aggregated and measured at the macroscopic level in averaged economic output
      quantities such as GDP. A fundamental question is thereby to what extent
      individual firm size fluctuations can have a noticeable impact on the overall
      economy. We argue that this question can be answered by considering the Levy
      fluctuations as embedded in a steep confining potential well, ensuring nonlinear
      mean-reversal behavior, without having to rely on microscopic details of the
      system. The steepness of the potential well directly controls the extent to which
      idiosyncratic shocks to firms and sectors are damped at the level of the economy.
      Additionally, the theory naturally accounts for business cycles, represented in
      terms of a bimodal economic output distribution and thus connects two so far
      unrelated fields in economics. By analyzing 200 years of U.S. gross domestic
      product growth rates, we find that the model is in good agreement with the data.

PMID- 29448427
TI  - Robust thresholdlike effect of internal noise on stochastic resonance in an
      organic field-effect transistor.
AB  - The application of noise to a nonlinear system can have the effect of increasing
      the signal transmission of the system through the phenomenon of stochastic
      resonance (SR). This paper presents an analytical characterization of the
      dependence of the signal transmission performance of an organic field-effect
      transistor (OFET) on external noise. Similarly to the threshold of a nonlinear
      system, the additive internal noise of the system can be used to control the
      emergence of SR. Internal noise or the addition of random numbers to the system
      enables one to observe the SR phenomenon in an OFET under an intrinsically
      nonresonant condition. Internal noise plays a thresholdlike role, but it
      functions in a different manner. The fluctuations in performance due to external
      noise become smaller when the effect of internal noise becomes dominant compared
      with that of the threshold. In conclusion, it is found that internal noise plays
      a robust thresholdlike role with respect to variations in external noise
      intensity.

PMID- 29448428
TI  - Polariton solitons and nonlinear localized states in a one-dimensional
      semiconductor microcavity.
AB  - This paper presents numerical studies of cavity polariton solitons (CPSs) in a
      resonantly pumped semiconductor microcavity with an imbedded spatial defect. In
      the bistable regime of the well-known homogeneous polariton condensate, with
      proper incident wave vector and pump strength, bright and/or dark cavity solitons
      can be found in the presence of a spatially confined potential. The minimum pump
      strength required to observe the CPSs or nonlinear localized states in this
      parametric pump scheme is therefore reported.

PMID- 29448429
TI  - Partial entropic stabilization of lattice Boltzmann magnetohydrodynamics.
AB  - The entropic lattice Boltzmann algorithm of Karlin et al. [Phys. Rev. E 90,
      031302 (2014)PLEEE81539-375510.1103/PhysRevE.90.031302] is partially extended to
      magnetohydrodynamics, based on the Dellar model of introducing a vector
      distribution for the magnetic field. This entropic ansatz is now applied only to
      the scalar particle distribution function so as to permit the many problems
      entailing magnetic field reversal. A 9-bit lattice is employed for both particle
      and magnetic distributions for our two-dimensional simulations. The entropic
      ansatz is benchmarked against our earlier multiple relaxation lattice-Boltzmann
      model for the Kelvin-Helmholtz instability in a magnetized jet. Other two
      dimensional simulations are performed and compared to results determined by more
      standard direct algorithms: in particular the switch over between the Kelvin
      Helmholtz or tearing mode instability of Chen et al. [J. Geophys. Res.: Space
      Phys. 102, 151 (1997)JGREA20148-022710.1029/96JA03144], and the generalized
      Orszag-Tang vortex model of Biskamp-Welter [Phys. Fluids B 1, 1964
      (1989)PFBPEI0899-822110.1063/1.859060]. Very good results are achieved.

PMID- 29448430
TI  - Social dilemmas in multistrategy evolutionary potential games.
AB  - The nature of social dilemmas is studied in n-strategy evolutionary potential
      games on a square lattice with nearest-neighbor interactions and the logit rule.
      For symmetric games with symmetric payoff matrices there are no dilemmas because
      of the coincidence of individual and common interests. The dilemmas are caused by
      the antisymmetric parts of the self- and cross-dependent payoff components if it
      modifies the preferred Nash equilibrium. The contentment of players and the
      emergence of dilemmas in the preferred Nash equilibria are illustrated on some
      two-dimensional cross sections of the parameter space.

PMID- 29448431
TI  - Structural stability of nonlinear population dynamics.
AB  - In population dynamics, the concept of structural stability has been used to
      quantify the tolerance of a system to environmental perturbations. Yet, measuring
      the structural stability of nonlinear dynamical systems remains a challenging
      task. Focusing on the classic Lotka-Volterra dynamics, because of the linearity
      of the functional response, it has been possible to measure the conditions
      compatible with a structurally stable system. However, the functional response of
      biological communities is not always well approximated by deterministic linear
      functions. Thus, it is unclear the extent to which this linear approach can be
      generalized to other population dynamics models. Here, we show that the same
      approach used to investigate the classic Lotka-Volterra dynamics, which is called
      the structural approach, can be applied to a much larger class of nonlinear
      models. This class covers a large number of nonlinear functional responses that
      have been intensively investigated both theoretically and experimentally. We also
      investigate the applicability of the structural approach to stochastic dynamical
      systems and we provide a measure of structural stability for finite populations.
      Overall, we show that the structural approach can provide reliable and tractable
      information about the qualitative behavior of many nonlinear dynamical systems.

PMID- 29448432
TI  - Effect of particle stiffness on contact dynamics and rheology in a dense granular
      flow.
AB  - Dense granular flows have been well described by the Bagnold rheology, even when
      the particles are in the multibody contact regime and the coordination number is
      greater than 1. This is surprising, because the Bagnold law should be applicable
      only in the instantaneous collision regime, where the time between collisions is
      much larger than the period of a collision. Here, the effect of particle
      stiffness on rheology is examined. It is found that there is a rheological
      threshold between a particle stiffness of 10^{4}-10^{5} for the linear contact
      model and 10^{5}-10^{6} for the Hertzian contact model above which Bagnold
      rheology (stress proportional to square of the strain rate) is valid and below
      which there is a power-law rheology, where all components of the stress and the
      granular temperature are proportional to a power of the strain rate that is less
      then 2. The system is in the multibody contact regime at the rheological
      threshold. However, the contact energy per particle is less than the kinetic
      energy per particle above the rheological threshold, and it becomes larger than
      the kinetic energy per particle below the rheological threshold. The distribution
      functions for the interparticle forces and contact energies are also analyzed.
      The distribution functions are invariant with height, but they do depend on the
      contact model. The contact energy distribution functions are well fitted by Gamma
      distributions. There is a transition in the shape of the distribution function as
      the particle stiffness is decreased from 10^{7} to 10^{6} for the linear model
      and 10^{8} to 10^{7} for the Hertzian model, when the contact number exceeds 1.
      Thus, the transition in the distribution function correlates to the contact
      regime threshold from the binary to multibody contact regime, and is clearly
      different from the rheological threshold. An order-disorder transition has
      recently been reported in dense granular flows. The Bagnold rheology applies for
      both the ordered and disordered states, even though the rheological constants
      differ by orders of magnitude. The effect of particle stiffness on the order
      disorder transition is examined here. It is found that when the particle
      stiffness is above the rheological threshold, there is an order-disorder
      transition as the base roughness is increased. The order-disorder transition
      disappears after the crossover to the soft-particle regime when the particle
      stiffness is decreased below the rheological threshold, indicating that the
      transition is a hard-particle phenomenon.

PMID- 29448433
TI  - Casimir amplitudes in topological quantum phase transitions.
AB  - Topological phase transitions constitute a new class of quantum critical
      phenomena. They cannot be described within the usual framework of the Landau
      theory since, in general, the different phases cannot be distinguished by an
      order parameter, neither can they be related to different symmetries. In most
      cases, however, one can identify a diverging length at these topological
      transitions. This allows us to describe them using a scaling approach and to
      introduce a set of critical exponents that characterize their universality class.
      Here we consider some relevant models of quantum topological transitions
      associated with well-defined critical exponents that are related by a quantum
      hyperscaling relation. We extend to these models a finite-size scaling approach
      based on techniques for calculating the Casimir force in electromagnetism. This
      procedure allows us to obtain universal Casimir amplitudes at their quantum
      critical points. Our results verify the validity of finite-size scaling in these
      systems and confirm the values of the critical exponents obtained previously.

PMID- 29448434
TI  - Three-body correlations and conditional forces in suspensions of active hard
      disks.
AB  - Self-propelled Brownian particles show rich out-of-equilibrium physics, for
      instance, the motility-induced phase separation (MIPS). While decades of studying
      the structure of liquids have established a deep understanding of passive
      systems, not much is known about correlations in active suspensions. In this work
      we derive an approximate analytic theory for three-body correlations and forces
      in systems of active Brownian disks starting from the many-body Smoluchowski
      equation. We use our theory to predict the conditional forces that act on a
      tagged particle and their dependence on the propulsion speed of self-propelled
      disks. We identify preferred directions of these forces in relation to the
      direction of propulsion and the positions of the surrounding particles. We
      further relate our theory to the effective swimming speed of the active disks,
      which is relevant for the physics of MIPS. To test and validate our theory, we
      additionally run particle-resolved computer simulations, for which we explicitly
      calculate the three-body forces. In this context, we discuss the modeling of
      active Brownian swimmers with nearly hard interaction potentials. We find very
      good agreement between our simulations and numerical solutions of our theory,
      especially for the nonequilibrium pair-distribution function. For our analytical
      results, we carefully discuss their range of validity in the context of the
      different levels of approximation we applied. This discussion allows us to study
      the individual contribution of particles to three-body forces and to the emerging
      structure. Thus, our work sheds light on the collective behavior, provides the
      basis for further studies of correlations in active suspensions, and makes a step
      towards an emerging liquid state theory.

PMID- 29448435
TI  - Shear-stress fluctuations and relaxation in polymer glasses.
AB  - We investigate by means of molecular dynamics simulation a coarse-grained polymer
      glass model focusing on (quasistatic and dynamical) shear-stress fluctuations as
      a function of temperature T and sampling time Deltat. The linear response is
      characterized using (ensemble-averaged) expectation values of the contributions
      (time averaged for each shear plane) to the stress-fluctuation relation MU_{sf}
      for the shear modulus and the shear-stress relaxation modulus G(t). Using 100
      independent configurations, we pay attention to the respective standard
      deviations. While the ensemble-averaged modulus MU_{sf}(T) decreases continuously
      with increasing T for all Deltat sampled, its standard deviation deltaMU_{sf}(T)
      is nonmonotonic with a striking peak at the glass transition. The question of
      whether the shear modulus is continuous or has a jump singularity at the glass
      transition is thus ill posed. Confirming the effective time-translational
      invariance of our systems, the Deltat dependence of MU_{sf} and related
      quantities can be understood using a weighted integral over G(t).

PMID- 29448436
TI  - Nonparametric weighted stochastic block models.
AB  - We present a Bayesian formulation of weighted stochastic block models that can be
      used to infer the large-scale modular structure of weighted networks, including
      their hierarchical organization. Our method is nonparametric, and thus does not
      require the prior knowledge of the number of groups or other dimensions of the
      model, which are instead inferred from data. We give a comprehensive treatment of
      different kinds of edge weights (i.e., continuous or discrete, signed or
      unsigned, bounded or unbounded), as well as arbitrary weight transformations, and
      describe an unsupervised model selection approach to choose the best network
      description. We illustrate the application of our method to a variety of
      empirical weighted networks, such as global migrations, voting patterns in
      congress, and neural connections in the human brain.

PMID- 29448437
TI  - Turbulent stagnation in a Z-pinch plasma.
AB  - The ion kinetic energy in a stagnating plasma was previously determined by Kroupp
      et al. [Phys. Rev. Lett. 107, 105001 (2011)PRLTAO0031
      900710.1103/PhysRevLett.107.105001] from Doppler-dominated line shapes augmented
      by measurements of plasma properties and assuming a uniform-plasma model.
      Notably, the energy was found to be dominantly stored in hydrodynamic flow. Here
      we advance a new description of this stagnation as supersonically turbulent. Such
      turbulence implies a nonuniform density distribution. We demonstrate how to
      reanalyze the spectroscopic data consistent with the turbulent picture and show
      that this leads to better concordance of the overconstrained spectroscopic
      measurements, while also substantially lowering the inferred mean density.

PMID- 29448438
TI  - Fourier heat conduction as a strong kinetic effect in one-dimensional hard-core
      gases.
AB  - For a one-dimensional (1D) momentum conserving system, intensive studies have
      shown that generally its heat current autocorrelation function (HCAF) tends to
      decay in a power-law manner and results in the breakdown of the Fourier heat
      conduction law in the thermodynamic limit. This has been recognized to be a
      dominant hydrodynamic effect. Here we show that, instead, the kinetic effect can
      be dominant in some cases and leads to the Fourier law for finite-size systems.
      Usually the HCAF undergoes a fast decaying kinetic stage followed by a long
      slowly decaying hydrodynamic tail. In a finite range of the system size, we find
      that whether the system follows the Fourier law depends on whether the kinetic
      stage dominates. Our Rapid Communication is illustrated by the 1D hard-core gas
      models with which the HCAF is derived analytically and verified numerically by
      molecular dynamics simulations.

PMID- 29448439
TI  - Modeling the complexity of acoustic emission during intermittent plastic
      deformation: Power laws and multifractal spectra.
AB  - Scale-invariant power-law distributions for acoustic emission signals are
      ubiquitous in several plastically deforming materials. However, power-law
      distributions for acoustic emission energies are reported in distinctly different
      plastically deforming situations such as hcp and fcc single and polycrystalline
      samples exhibiting smooth stress-strain curves and in dilute metallic alloys
      exhibiting discontinuous flow. This is surprising since the underlying
      dislocation mechanisms in these two types of deformations are very different. So
      far, there have been no models that predict the power-law statistics for
      discontinuous flow. Furthermore, the statistics of the acoustic emission signals
      in jerky flow is even more complex, requiring multifractal measures for a proper
      characterization. There has been no model that explains the complex statistics
      either. Here we address the problem of statistical characterization of the
      acoustic emission signals associated with the three types of the Portevin-Le
      Chatelier bands. Following our recently proposed general framework for
      calculating acoustic emission, we set up a wave equation for the elastic degrees
      of freedom with a plastic strain rate as a source term. The energy dissipated
      during acoustic emission is represented by the Rayleigh-dissipation function.
      Using the plastic strain rate obtained from the Ananthakrishna model for the
      Portevin-Le Chatelier effect, we compute the acoustic emission signals associated
      with the three Portevin-Le Chatelier bands and the Luders-like band. The so
      calculated acoustic emission signals are used for further statistical
      characterization. Our results show that the model predicts power-law statistics
      for all the acoustic emission signals associated with the three types of Portevin
      Le Chatelier bands with the exponent values increasing with increasing strain
      rate. The calculated multifractal spectra corresponding to the acoustic emission
      signals associated with the three band types have a maximum spread for the type C
      bands and decreasing with types B and A. We further show that the acoustic
      emission signals associated with Luders-like band also exhibit a power-law
      distribution and multifractality.

PMID- 29448440
TI  - Thermodynamics and computation during collective motion near criticality.
AB  - We study self-organization of collective motion as a thermodynamic phenomenon in
      the context of the first law of thermodynamics. It is expected that the coherent
      ordered motion typically self-organises in the presence of changes in the
      (generalized) internal energy and of (generalized) work done on, or extracted
      from, the system. We aim to explicitly quantify changes in these two quantities
      in a system of simulated self-propelled particles and contrast them with changes
      in the system's configuration entropy. In doing so, we adapt a thermodynamic
      formulation of the curvatures of the internal energy and the work, with respect
      to two parameters that control the particles' alignment. This allows us to
      systematically investigate the behavior of the system by varying the two control
      parameters to drive the system across a kinetic phase transition. Our results
      identify critical regimes and show that during the phase transition, where the
      configuration entropy of the system decreases, the rates of change of the work
      and of the internal energy also decrease, while their curvatures diverge.
      Importantly, the reduction of entropy achieved through expenditure of work is
      shown to peak at criticality. We relate this both to a thermodynamic efficiency
      and the significance of the increased order with respect to a computational path.
      Additionally, this study provides an information-geometric interpretation of the
      curvature of the internal energy as the difference between two curvatures: the
      curvature of the free entropy, captured by the Fisher information, and the
      curvature of the configuration entropy.

PMID- 29448441
TI  - Criticality of O(N) symmetric models in the presence of discrete gauge
      symmetries.
AB  - We investigate the critical properties of the three-dimensional antiferromagnetic
      RP^{N-1} model, which is characterized by a global O(N) symmetry and a discrete
      Z_{2} gauge symmetry. We perform a field-theoretical analysis using the Landau
      Ginzburg-Wilson (LGW) approach and a numerical Monte Carlo study. The LGW field
      theoretical results are obtained by high-order perturbative analyses of the
      renormalization-group flow of the most general Phi^{4} theory with the same
      global symmetry as the model, assuming a gauge-invariant order-parameter field.
      For N=4 no stable fixed point is found, implying that any transition must
      necessarily be of first order. This is contradicted by the numerical results that
      provide strong evidence for a continuous transition. This suggests that gauge
      modes are not always irrelevant, as assumed by the LGW approach, but they may
      play an important role to determine the actual critical dynamics at the phase
      transition of O(N) symmetric models with a discrete Z_{2} gauge symmetry.

PMID- 29448442
TI  - Publisher's Note: Relaxation-type nonlocal inertial-number rheology for dry
      granular flows [Phys. Rev. E 96, 062909 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.96.062909.

PMID- 29448443
TI  - Two-length-scale turbulence model for self-similar buoyancy-, shock-, and shear
      driven mixing.
AB  - The three-equation k-L-a turbulence model [B. Morgan and M. Wickett, Three
      equation model for the self-similar growth of Rayleigh-Taylor and Richtmyer
      Meshkov instabilities, Phys. Rev. E 91, 043002 (2015)PLEEE81539
      375510.1103/PhysRevE.91.043002] is extended by the addition of a second length
      scale equation. It is shown that the separation of turbulence transport and
      turbulence destruction length scales is necessary for simultaneous prediction of
      the growth parameter and turbulence intensity of a Kelvin-Helmholtz shear layer
      when model coefficients are constrained by similarity analysis. Constraints on
      model coefficients are derived that satisfy an ansatz of self-similarity in the
      low-Atwood-number limit and allow the determination of model coefficients
      necessary to recover expected experimental behavior. The model is then applied in
      one-dimensional simulations of Rayleigh-Taylor, reshocked Richtmyer-Meshkov,
      Kelvin-Helmholtz, and combined Rayleigh-Taylor-Kelvin-Helmholtz instability
      mixing layers to demonstrate that the expected growth rates are recovered
      numerically. Finally, it is shown in the case of combined instability that the
      model predicts a mixing width that is a linear combination of Rayleigh-Taylor and
      Kelvin-Helmholtz mixing processes.

PMID- 29448444
TI  - Stress distribution in two-dimensional silos.
AB  - Simulations of a polydispersed two-dimensional silo were performed using
      molecular dynamics, with different numbers of grains reaching up to 64 000,
      verifying numerically the model derived by Janssen and also the main assumption
      that the walls carry part of the weight due to the static friction between grains
      with themselves and those with the silo's walls. We vary the friction
      coefficient, the radii dispersity, the silo width, and the size of grains. We
      find that the Janssen's model becomes less relevant as the the silo width
      increases since the behavior of the stresses becomes more hydrostatic. Likewise,
      we get the normal and tangential stress distribution on the walls evidencing the
      existence of points of maximum stress. We also obtained the stress matrix with
      which we observe zones of concentration of load, located always at a height
      around two thirds of the granular columns. Finally, we observe that the size of
      the grains affects the distribution of stresses, increasing the weight on the
      bottom and reducing the normal stress on the walls, as the grains are made
      smaller (for the same total mass of the granulate), giving again a more
      hydrostatic and therefore less Janssen-type behavior for the weight of the
      column.

PMID- 29448445
TI  - Collective excitability in a mesoscopic neuronal model of epileptic activity.
AB  - At the mesoscopic scale, the brain can be understood as a collection of
      interacting neuronal oscillators, but the extent to which its sustained activity
      is due to coupling among brain areas is still unclear. Here we address this issue
      in a simplified situation by examining the effect of coupling between two
      cortical columns described via Jansen-Rit neural mass models. Our results show
      that coupling between the two neuronal populations gives rise to stochastic
      initiations of sustained collective activity, which can be interpreted as
      epileptic events. For large enough coupling strengths, termination of these
      events results mainly from the emergence of synchronization between the columns,
      and thus it is controlled by coupling instead of noise. Stochastic triggering and
      noise-independent durations are characteristic of excitable dynamics, and thus we
      interpret our results in terms of collective excitability.

PMID- 29448446
TI  - Origin and scaling of chaos in weakly coupled phase oscillators.
AB  - We discuss the behavior of the largest Lyapunov exponent lambda in the incoherent
      phase of large ensembles of heterogeneous, globally coupled, phase oscillators.
      We show that the scaling with the system size N depends on the details of the
      spacing distribution of the oscillator frequencies. For sufficiently regular
      distributions lambda~1/N, while for strong fluctuations of the frequency spacing
      lambda~lnN/N (the standard setup of independent identically distributed variables
      belongs to the latter class). In spite of the coupling being small for large N,
      the development of a rigorous perturbative theory is not obvious. In fact, our
      analysis relies on a combination of various types of numerical simulations
      together with approximate analytical arguments, based on a suitable stochastic
      approximation for the tangent space evolution. In fact, the very reason for
      lambda being strictly larger than zero is the presence of finite-size
      fluctuations. We trace back the origin of the logarithmic correction to a weak
      synchronization between tangent and phase-space dynamics.

PMID- 29448447
TI  - Nonuniversal and anomalous critical behavior of the contact process near an
      extended defect.
AB  - We consider the contact process near an extended surface defect, where the local
      control parameter deviates from the bulk one by an amount of lambda(l)
      lambda(infinity)=Al^{-s}, with l being the distance from the surface. We
      concentrate on the marginal situation s=1/nu_{?}, where nu_{?} is the critical
      exponent of the spatial correlation length, and study the local critical
      properties of the one-dimensional model by Monte Carlo simulations. The system
      exhibits a rich surface critical behavior. For weaker local activation rates
      A<A_{c}, the phase transition is continuous, having an order-parameter critical
      exponent, which varies continuously with A. For stronger local activation rates
      A>A_{c}, the phase transition is of mixed order: the surface order parameter is
      discontinuous; at the same time the temporal correlation length diverges
      algebraically as the critical point is approached, but with different exponents
      on the two sides of the transition. The mixed-order transition regime is
      analogous to that observed recently at a multiple junction and can be explained
      by the same type of scaling theory.

PMID- 29448448
TI  - High-speed broadband elastic actuator in water using induced-charge electro
      osmosis with a skew structure.
AB  - An artificial cilium using ac electro-osmosis (ACEO) is attractive because of its
      large potentiality for innovative microfluidic applications. However, the ACEO
      cilium has not been probed experimentally and has a shortcoming that the working
      frequency range is very narrow. Thus, we here propose an ACEO elastic actuator
      having a skew structure that broadens a working frequency range and
      experimentally demonstrate that the elastic actuator in water can be driven with
      a high-speed (~10 Hz) and a wide frequency range (~0.1 to ~10 kHz). Moreover, we
      propose a simple self-consistent model that explains the broadband characteristic
      due to the skew structure with other characteristics. By comparing the
      theoretical results with the experimental results, we find that they agree fairly
      well. We believe that our ACEO elastic actuator will play an important role in
      microfluidics in the future.

PMID- 29448449
TI  - Unsupervised machine learning account of magnetic transitions in the Hubbard
      model.
AB  - We employ several unsupervised machine learning techniques, including
      autoencoders, random trees embedding, and t-distributed stochastic neighboring
      ensemble (t-SNE), to reduce the dimensionality of, and therefore classify, raw
      (auxiliary) spin configurations generated, through Monte Carlo simulations of
      small clusters, for the Ising and Fermi-Hubbard models at finite temperatures.
      Results from a convolutional autoencoder for the three-dimensional Ising model
      can be shown to produce the magnetization and the susceptibility as a function of
      temperature with a high degree of accuracy. Quantum fluctuations distort this
      picture and prevent us from making such connections between the output of the
      autoencoder and physical observables for the Hubbard model. However, we are able
      to define an indicator based on the output of the t-SNE algorithm that shows a
      near perfect agreement with the antiferromagnetic structure factor of the model
      in two and three spatial dimensions in the weak-coupling regime. t-SNE also
      predicts a transition to the canted antiferromagnetic phase for the three
      dimensional model when a strong magnetic field is present. We show that these
      techniques cannot be expected to work away from half filling when the "sign
      problem" in quantum Monte Carlo simulations is present.

PMID- 29448450
TI  - Nonlinear excitation of the ablative Rayleigh-Taylor instability for all wave
      numbers.
AB  - Small-scale perturbations in the ablative Rayleigh-Taylor instability (ARTI) are
      often neglected because they are linearly stable when their wavelength is shorter
      than a linear cutoff. Using two-dimensional (2D) and three-dimensional (3D)
      numerical simulations, it is shown that linearly stable modes of any wavelength
      can be destabilized. This instability regime requires finite amplitude initial
      perturbations and linearly stable ARTI modes to be more easily destabilized in 3D
      than in 2D. It is shown that for conditions found in laser fusion targets, short
      wavelength ARTI modes are more efficient at driving mixing of ablated material
      throughout the target since the nonlinear bubble density increases with the wave
      number and small-scale bubbles carry a larger mass flux of mixed material.

PMID- 29448451
TI  - Erratum: Physics of giant electromagnetic pulse generation in short-pulse laser
      experiments [Phys. Rev. E 91, 043106 (2015)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.91.043106.

PMID- 29448452
TI  - Connection between nonlinear energy optimization and instantons.
AB  - How systems transit between different stable states under external perturbation
      is an important practical issue. We discuss here how a recently developed energy
      optimization method for identifying the minimal disturbance necessary to reach
      the basin boundary of a stable state is connected to the instanton trajectory
      from large deviation theory of noisy systems. In the context of the one
      dimensional Swift-Hohenberg equation, which has multiple stable equilibria, we
      first show how the energy optimization method can be straightforwardly used to
      identify minimal disturbances-minimal seeds-for transition to specific attractors
      from the ground state. Then, after generalizing the technique to consider
      multiple, equally spaced-in-time perturbations, it is shown that the instanton
      trajectory is indeed the solution of the energy optimization method in the limit
      of infinitely many perturbations provided a specific norm is used to measure the
      set of discrete perturbations. Importantly, we find that the key features of the
      instanton can be captured by a low number of discrete perturbations (typically
      one perturbation per basin of attraction crossed). This suggests a promising new
      diagnostic for systems for which it may be impractical to calculate the
      instanton.

PMID- 29448453
TI  - Electroneutral models for dynamic Poisson-Nernst-Planck systems.
AB  - The Poisson-Nernst-Planck (PNP) system is a standard model for describing ion
      transport. In many applications, e.g., ions in biological tissues, the presence
      of thin boundary layers poses both modeling and computational challenges. In this
      paper, we derive simplified electroneutral (EN) models where the thin boundary
      layers are replaced by effective boundary conditions. There are two major
      advantages of EN models. First, it is much cheaper to solve them numerically.
      Second, EN models are easier to deal with compared to the original PNP system;
      therefore, it would also be easier to derive macroscopic models for cellular
      structures using EN models. Even though the approach used here is applicable to
      higher-dimensional cases, this paper mainly focuses on the one-dimensional
      system, including the general multi-ion case. Using systematic asymptotic
      analysis, we derive a variety of effective boundary conditions directly
      applicable to the EN system for the bulk region. This EN system can be solved
      directly and efficiently without computing the solution in the boundary layer.
      The derivation is based on matched asymptotics, and the key idea is to bring back
      higher-order contributions into the effective boundary conditions. For Dirichlet
      boundary conditions, the higher-order terms can be neglected and the classical
      results (continuity of electrochemical potential) are recovered. For flux
      boundary conditions, higher-order terms account for the accumulation of ions in
      boundary layer and neglecting them leads to physically incorrect solutions. To
      validate the EN model, numerical computations are carried out for several
      examples. Our results show that solving the EN model is much more efficient than
      the original PNP system. Implemented with the Hodgkin-Huxley model, the
      computational time for solving the EN model is significantly reduced without
      sacrificing the accuracy of the solution due to the fact that it allows for
      relatively large mesh and time-step sizes.

PMID- 29448454
TI  - Uniaxial and biaxial structures in the elastic Maier-Saupe model.
AB  - We perform statistical mechanics calculations to analyze the global phase diagram
      of a fully connected version of a Maier-Saupe-Zwanzig lattice model with the
      inclusion of couplings to an elastic strain field. We point out the presence of
      uniaxial and biaxial nematic structures, depending on temperature T and on the
      applied stress sigma. Under uniaxial extensive tension, applied stress favors
      uniaxial orientation, and we obtain a first-order boundary along which there is a
      coexistence of two uniaxial paranematic phases, and which ends at a simple
      critical point. Under uniaxial compressive tension, stress favors biaxial
      orientation; for small values of the coupling parameters, the first-order
      boundary ends at a tricritical point, beyond which there is a continuous
      transition between a paranematic and a biaxially ordered structure. For some
      representative choices of the model parameters, we obtain a number of analytic
      results, including the location of critical and tricritical points and the line
      of stability of the biaxial phase.

PMID- 29448455
TI  - Triviality of the ground-state metastate in long-range Ising spin glasses in one
      dimension.
AB  - We consider the one-dimensional model of a spin glass with independent Gaussian
      distributed random interactions, which have mean zero and variance 1/|i
      j|^{2sigma}, between the spins at sites i and j for all i?j. It is known that,
      for sigma>1, there is no phase transition at any nonzero temperature in this
      model. We prove rigorously that, for sigma>3/2, any translation-covariant Newman
      Stein metastate for the ground states (i.e., the frequencies with which distinct
      ground states are observed in finite-size samples in the limit of infinite size,
      for given disorder) is trivial and unique. In other words, for given disorder and
      asymptotically at large sizes, the same ground state, or its global spin flip, is
      obtained (almost) always. The proof consists of two parts: One is a theorem
      (based on one by Newman and Stein for short-range two-dimensional models), valid
      for all sigma>1, that establishes triviality under a convergence hypothesis on
      something similar to the energies of domain walls and the other (based on older
      results for the one-dimensional model) establishes that the hypothesis is true
      for sigma>3/2. In addition, we derive heuristic scaling arguments and rigorous
      exponent inequalities which tend to support the validity of the hypothesis under
      broader conditions. The constructions of various metastates are extended to all
      values sigma>1/2. Triviality of the metastate in bond-diluted power-law models
      for sigma>1 is proved directly.

PMID- 29448456
TI  - Flow of colloidal suspensions through small orifices.
AB  - In this work, we numerically study a dense colloidal suspension flowing through a
      small outlet driven by a pressure drop using lattice-Boltzmann methods. This
      system shows intermittent flow regimes that precede clogging events. Several
      pieces of evidence suggest that the temperature controls the dynamic state of the
      system when the driving force and the aperture size are fixed. When the
      temperature is low, the suspension's flow can be interrupted during long time
      periods, which can be even two orders of magnitude larger than the system's
      characteristic time (Stokes). We also find that strong thermal noise does not
      allow the formation of stable aggregate structures avoiding extreme clogging
      events, but, at the same time, it randomizes the particle trajectories and
      disturbs the advective particle flow through the aperture. Moreover, examining
      the particle velocity statistics, we obtain that in the plane normal to the
      pressure drop the colloids always move as free particles regardless of the
      temperature value. In the pressure drop direction, at high temperature the
      colloids experience a simple balance between advective and diffusive transport,
      but at low temperature the nature of the flow is much more complex, correlating
      with the occurrence of very long clogging events.

PMID- 29448457
TI  - Exact law for homogeneous compressible Hall magnetohydrodynamics turbulence.
AB  - We derive an exact law for three-dimensional (3D) homogeneous compressible
      isothermal Hall magnetohydrodynamic turbulence, without the assumption of
      isotropy. The Hall current is shown to introduce new flux and source terms that
      act at the small scales (comparable or smaller than the ion skin depth) to
      significantly impact the turbulence dynamics. The law provides an accurate means
      to estimate the energy cascade rate over a broad range of scales covering the
      magnetohydrodynamic inertial range and the sub-ion dispersive range in 3D
      numerical simulations and in in situ spacecraft observations of compressible
      turbulence. This work is particularly relevant to astrophysical flows in which
      small-scale density fluctuations cannot be ignored such as the solar wind,
      planetary magnetospheres, and the interstellar medium.

PMID- 29448459
TI  - Announcement: Corrections in Physical Review publications.

PMID- 29448458
TI  - Mechanical stress as a regulator of cell motility.
AB  - The motility of a cell can be triggered or inhibited not only by an applied force
      but also by a mechanically neutral force couple. This type of loading,
      represented by an applied stress and commonly interpreted as either squeezing or
      stretching, can originate from extrinsic interaction of a cell with its
      neighbors. To quantify the effect of applied stresses on cell motility we use an
      analytically transparent one-dimensional model accounting for active myosin
      contraction and induced actin turnover. We show that stretching can polarize
      static cells and initiate cell motility while squeezing can symmetrize and arrest
      moving cells. We show further that sufficiently strong squeezing can lead to the
      loss of cell integrity. The overall behavior of the system depends on the two
      dimensionless parameters characterizing internal driving (chemical activity) and
      external loading (applied stress). We construct a phase diagram in this parameter
      space distinguishing between static, motile, and collapsed states. The obtained
      results are relevant for the mechanical understanding of contact inhibition and
      the epithelial-to-mesenchymal transition.

PMID- 29448460
TI  - Correlation versus randomization of jerky flow in an AlMgScZr alloy using
      acoustic emission.
AB  - Jerky flow in solids results from collective dynamics of dislocations which gives
      rise to serrated deformation curves and a complex evolution of the strain
      heterogeneity. A rich example of this phenomenon is the Portevin-Le Chatelier
      effect in alloys. The corresponding spatiotemporal patterns showed some universal
      features which provided a basis for a well-known phenomenological classification.
      Recent studies revealed peculiar features in both the stress serration sequences
      and the kinematics of deformation bands in Al-based alloys containing fine
      microstructure elements, such as nanosize precipitates and/or submicron grains.
      In the present work, jerky flow of an AlMgScZr alloy is studied using statistical
      analysis of stress serrations and the accompanying acoustic emission. As in the
      case of coarse-grained binary AlMg alloys, the amplitude distributions of
      acoustic events obey a power-law scaling which is usually considered as evidence
      of avalanchelike dynamics. However, the scaling exponents display specific
      dependences on the strain and strain rate for the investigated materials. The
      observed effects bear evidence to a competition between the phenomena of
      synchronization and randomization of dislocation avalanches, which may shed light
      on the mechanisms leading to a high variety of jerky flow patterns observed in
      applied alloys.

PMID- 29448461
TI  - Publisher's Note: Inverse Ising problem in continuous time: A latent variable
      approach [Phys. Rev. E 96, 062104 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.96.062104.

PMID- 29448462
TI  - Stochastic quantum thermodynamics, entropy production, and transport properties
      of a bosonic system.
AB  - The transport properties of a bosonic chain have been calculated by placing the
      ends of the chain in contact with thermal and particle reservoirs at different
      temperatures and chemical potentials. The contact with the reservoirs is
      described by the use of a quantum Fokker-Planck-Kramers equation, which is a
      canonical quantization of the classical Fokker-Planck-Kramers equation. From the
      quantum equation we obtain equations for the covariances of the creation and
      annihilation boson operators and solve them in the stationary state for small
      interactions. From the covariances we determine the Onsager coefficients and in
      particular the conductance, which was found to be finite for any chain size
      leading to an infinite conductivity and the absence of Fourier's law.

PMID- 29448463
TI  - Effective equilibrium states in mixtures of active particles driven by colored
      noise.
AB  - We consider the steady-state behavior of pairs of active particles having
      different persistence times and diffusivities. To this purpose we employ the
      active Ornstein-Uhlenbeck model, where the particles are driven by colored noises
      with exponential correlation functions whose intensities and correlation times
      vary from species to species. By extending Fox's theory to many components, we
      derive by functional calculus an approximate Fokker-Planck equation for the
      configurational distribution function of the system. After illustrating the
      predicted distribution in the solvable case of two particles interacting via a
      harmonic potential, we consider systems of particles repelling through inverse
      power-law potentials. We compare the analytic predictions to computer simulations
      for such soft-repulsive interactions in one dimension and show that at linear
      order in the persistence times the theory is satisfactory. This work provides the
      toolbox to qualitatively describe many-body phenomena, such as demixing and
      depletion, by means of effective pair potentials.

PMID- 29448464
TI  - Group-wave resonances in nonlinear dispersive media: The case of gravity water
      waves.
AB  - The dynamics of coherent nonlinear wave groups is shown to be drastically
      different from the classical scenario of weakly nonlinear wave interactions. The
      coherent groups generate nonresonant (bound) waves which can be synchronized with
      other linear waves. By virtue of the revealed mechanism, the groups may emit
      waves with similar or different lengths, which propagate in the same or opposite
      direction.

PMID- 29448465
TI  - Universal scaling and nonlinearity of aggregate price impact in financial
      markets.
AB  - How and why stock prices move is a centuries-old question still not answered
      conclusively. More recently, attention shifted to higher frequencies, where
      trades are processed piecewise across different time scales. Here we reveal that
      price impact has a universal nonlinear shape for trades aggregated on any
      intraday scale. Its shape varies little across instruments, but drastically
      different master curves are obtained for order-volume and -sign impact. The
      scaling is largely determined by the relevant Hurst exponents. We further show
      that extreme order-flow imbalance is not associated with large returns. To the
      contrary, it is observed when the price is pinned to a particular level. Prices
      move only when there is sufficient balance in the local order flow. In fact, the
      probability that a trade changes the midprice falls to zero with increasing
      (absolute) order-sign bias along an arc-shaped curve for all intraday scales. Our
      findings challenge the widespread assumption of linear aggregate impact. They
      imply that market dynamics on all intraday time scales are shaped by correlations
      and bilateral adaptation in the flows of liquidity provision and taking.

PMID- 29448466
TI  - Level crossings and excess times due to a superposition of uncorrelated
      exponential pulses.
AB  - A well-known stochastic model for intermittent fluctuations in physical systems
      is investigated. The model is given by a superposition of uncorrelated
      exponential pulses, and the degree of pulse overlap is interpreted as an
      intermittency parameter. Expressions for excess time statistics, that is, the
      rate of level crossings above a given threshold and the average time spent above
      the threshold, are derived from the joint distribution of the process and its
      derivative. Limits of both high and low intermittency are investigated and
      compared to previously known results. In the case of a strongly intermittent
      process, the distribution of times spent above threshold is obtained
      analytically. This expression is verified numerically, and the distribution of
      times above threshold is explored for other intermittency regimes. The numerical
      simulations compare favorably to known results for the distribution of times
      above the mean threshold for an Ornstein-Uhlenbeck process. This contribution
      generalizes the excess time statistics for the stochastic model, which find
      applications in a wide diversity of natural and technological systems.

PMID- 29448467
TI  - Lattice Boltzmann model for high-order nonlinear partial differential equations.
AB  - In this paper, a general lattice Boltzmann (LB) model is proposed for the high
      order nonlinear partial differential equation with the form
      ?_{t}phi+?_{k=1}^{m}alpha_{k}?_{x}^{k}Pi_{k}(phi)=0 (1<=k<=m<=6), alpha_{k} are
      constant coefficients, Pi_{k}(phi) are some known differential functions of phi.
      As some special cases of the high-order nonlinear partial differential equation,
      the classical (m)KdV equation, KdV-Burgers equation, K(n,n)-Burgers equation,
      Kuramoto-Sivashinsky equation, and Kawahara equation can be solved by the present
      LB model. Compared to the available LB models, the most distinct characteristic
      of the present model is to introduce some suitable auxiliary moments such that
      the correct moments of equilibrium distribution function can be achieved. In
      addition, we also conducted a detailed Chapman-Enskog analysis, and found that
      the high-order nonlinear partial differential equation can be correctly recovered
      from the proposed LB model. Finally, a large number of simulations are performed,
      and it is found that the numerical results agree with the analytical solutions,
      and usually the present model is also more accurate than the existing LB models
      [H. Lai and C. Ma, Sci. China Ser. G 52, 1053 (2009)1672-179910.1007/s11433-009
      0149-3; H. Lai and C. Ma, Phys. A (Amsterdam) 388, 1405 (2009)PHYADX0378
      437110.1016/j.physa.2009.01.005] for high-order nonlinear partial differential
      equations.

PMID- 29448468
TI  - Memory-induced resonancelike suppression of spike generation in a resonate-and
      fire neuron model.
AB  - The behavior of a stochastic resonate-and-fire neuron model based on a reduction
      of a fractional noise-driven generalized Langevin equation (GLE) with a power-law
      memory kernel is considered. The effect of temporally correlated random activity
      of synaptic inputs, which arise from other neurons forming local and distant
      networks, is modeled as an additive fractional Gaussian noise in the GLE. Using a
      first-passage-time formulation, in certain system parameter domains exact
      expressions for the output interspike interval (ISI) density and for the survival
      probability (the probability that a spike is not generated) are derived and their
      dependence on input parameters, especially on the memory exponent, is analyzed.
      In the case of external white noise, it is shown that at intermediate values of
      the memory exponent the survival probability is significantly enhanced in
      comparison with the cases of strong and weak memory, which causes a resonancelike
      suppression of the probability of spike generation as a function of the memory
      exponent. Moreover, an examination of the dependence of multimodality in the ISI
      distribution on input parameters shows that there exists a critical memory
      exponent alpha_{c}~0.402, which marks a dynamical transition in the behavior of
      the system. That phenomenon is illustrated by a phase diagram describing the
      emergence of three qualitatively different structures of the ISI distribution.
      Similarities and differences between the behavior of the model at internal and
      external noises are also discussed.

PMID- 29448470
TI  - Optimal design of tweezer control for chimera states.
AB  - Chimera states are complex spatio-temporal patterns which consist of coexisting
      domains of spatially coherent and incoherent dynamics in systems of coupled
      oscillators. In small networks, chimera states usually exhibit short lifetimes
      and erratic drifting of the spatial position of the incoherent domain. A tweezer
      feedback control scheme can stabilize and fix the position of chimera states. We
      analyze the action of the tweezer control in small nonlocally coupled networks of
      Van der Pol and FitzHugh-Nagumo oscillators, and determine the ranges of optimal
      control parameters. We demonstrate that the tweezer control scheme allows for
      stabilization of chimera states with different shapes, and can be used as an
      instrument for controlling the coherent domains size, as well as the maximum
      average frequency difference of the oscillators.

PMID- 29448469
TI  - Regulating positioning and orientation of mitotic spindles via cell size and
      shape.
AB  - Proper location of the mitotic spindle is critical for chromosome segregation and
      the selection of the cell division plane. However, how mitotic spindles sense
      cell size and shape to regulate their own position and orientation is still
      largely unclear. To investigate this question systematically, we used a general
      model by considering chromosomes, microtubule dynamics, and forces of various
      molecular motors. Our results show that in cells of various sizes and shapes,
      spindles can always be centered and oriented along the long axis robustly in the
      absence of other specified mechanisms. We found that the characteristic time of
      positioning and orientation processes increases with cell size. Spindles sense
      the cell size mainly by the cortical force in small cells and by the cytoplasmic
      force in large cells. In addition to the cell size, the cell shape mainly
      influences the orientation process. We found that more slender cells have a
      faster orientation process, and the final orientation is not necessarily along
      the longest axis but is determined by the radial profile and the symmetry of the
      cell shape. Finally, our model also reproduces the separation and repositioning
      of the spindle poles during the anaphase. Therefore, our work provides a general
      tool for studying the mitotic spindle across the whole mitotic phase.

PMID- 29448471
TI  - Generation of anisotropy in turbulent flows subjected to rapid distortion.
AB  - A computational tool for the anisotropic time-evolution of the spectral velocity
      correlation tensor is presented. We operate in the linear, rapid distortion limit
      of the mean-field-coupled equations. Each term of the equations is written in the
      form of an expansion to arbitrary order in the basis of irreducible
      representations of the SO(3) symmetry group. The computational algorithm for this
      calculation solves a system of coupled equations for the scalar weights of each
      generated anisotropic mode. The analysis demonstrates that rapid distortion
      rapidly but systematically generates higher-order anisotropic modes. To maintain
      a tractable computation, the maximum number of rotational modes to be used in a
      given calculation is specified a priori. The computed Reynolds stress converges
      to the theoretical result derived by Batchelor and Proudman [Quart. J. Mech.
      Appl. Math. 7, 83 (1954)QJMMAV0033-561410.1093/qjmam/7.1.83] if a sufficiently
      large maximum number of rotational modes is utilized; more modes are required to
      recover the solution at later times. The emergence and evolution of the
      underlying multidimensional space of functions is presented here using a 64-mode
      calculation. Alternative implications for modeling strategies are discussed.

PMID- 29448472
TI  - Permutation glass.
AB  - The field of disordered systems in statistical physics provides many simple
      models in which the competing influences of thermal and nonthermal disorder lead
      to new phases and nontrivial thermal behavior of order parameters. In this paper,
      we add a model to the subject by considering a disordered system where the state
      space consists of various orderings of a list. As in spin glasses, the disorder
      of such "permutation glasses" arises from a parameter in the Hamiltonian being
      drawn from a distribution of possible values, thus allowing nominally "incorrect
      orderings" to have lower energies than "correct orderings" in the space of
      permutations. We analyze a Gaussian, uniform, and symmetric Bernoulli
      distribution of energy costs, and, by employing Jensen's inequality, derive a
      simple condition requiring the permutation glass to always transition to the
      correctly ordered state at a temperature lower than that of the nondisordered
      system, provided that this correctly ordered state is accessible. We in turn find
      that in order for the correctly ordered state to be accessible, the probability
      that an incorrectly ordered component is energetically favored must be less than
      the inverse of the number of components in the system. We show that all of these
      results are consistent with a replica symmetric ansatz of the system. We conclude
      by arguing that there is no distinct permutation glass phase for the simplest
      model considered here and by discussing how to extend the analysis to more
      complex Hamiltonians capable of novel phase behavior and replica symmetry
      breaking. Finally, we outline an apparent correspondence between the presented
      system and a discrete-energy-level fermion gas. In all, the investigation
      introduces a class of exactly soluble models into statistical mechanics and
      provides a fertile ground to investigate statistical models of disorder.

PMID- 29448473
TI  - Enhanced diffusion with abnormal temperature dependence in underdamped space
      periodic systems subject to time-periodic driving.
AB  - We present a study of the diffusion enhancement of underdamped Brownian particles
      in a one-dimensional symmetric space-periodic potential due to external symmetric
      time-periodic driving with zero mean. We show that the diffusivity can be
      enhanced by many orders of magnitude at an appropriate choice of the driving
      amplitude and frequency. The diffusivity demonstrates abnormal (decreasing)
      temperature dependence at the driving amplitudes exceeding a certain value. At
      any fixed driving frequency Omega normal temperature dependence of the
      diffusivity is restored at low enough temperatures, T<T_{TAD}(Omega)-in contrast
      with the problem with constant external driving. At fixed temperature at small
      driving frequency the diffusivity either slowly decreases with Omega, or (at
      stronger driving) goes through a maximum near Omega_{2}, the reciprocal
      superdiffusion regime termination time. At high frequencies, between Omega_{2}
      and a fraction of the oscillation frequency at the potential minimum, the
      diffusivity is shown to decrease with Omega according to a power law, with the
      exponent related to the transient superdiffusion exponent. This behavior is found
      similar for the cases of sinusoidal in time and piecewise constant periodic
      ("square") driving.

PMID- 29448474
TI  - Generic first-order phase transitions between isotropic and orientational phases
      with polyhedral symmetries.
AB  - Polyhedral nematics are examples of exotic orientational phases that possess a
      complex internal symmetry, representing highly nontrivial ways of rotational
      symmetry breaking, and are subject to current experimental pursuits in colloidal
      and molecular systems. The classification of these phases has been known for a
      long time; however, their transitions to the disordered isotropic liquid phase
      remain largely unexplored, except for a few symmetries. In this work, we utilize
      a recently introduced non-Abelian gauge theory to explore the nature of the
      underlying nematic-isotropic transition for all three-dimensional polyhedral
      nematics. The gauge theory can readily be applied to nematic phases with an
      arbitrary point-group symmetry, including those where traditional Landau methods
      and the associated lattice models may become too involved to implement owing to a
      prohibitive order-parameter tensor of high rank or (the absence of) mirror
      symmetries. By means of exhaustive Monte Carlo simulations, we find that the
      nematic-isotropic transition is generically first-order for all polyhedral
      symmetries. Moreover, we show that this universal result is fully consistent with
      our expectation from a renormalization group approach, as well as with other
      lattice models for symmetries already studied in the literature. We argue that
      extreme fine tuning is required to promote those transitions to second-order
      ones. We also comment on the nature of phase transitions breaking the O(3)
      symmetry in general cases.

PMID- 29448475
TI  - First-passage times in renewal and nonrenewal systems.
AB  - Fluctuations in stochastic systems are usually characterized by full counting
      statistics, which analyzes the distribution of the number of events taking place
      in the fixed time interval. In an alternative approach, the distribution of the
      first-passage times, i.e., the time delays after which the counting variable
      reaches a certain threshold value, is studied. This paper presents the approach
      to calculate the first-passage time distribution in systems in which the analyzed
      current is associated with an arbitrary set of transitions within the Markovian
      network. Using this approach, it is shown that when the subsequent first-passage
      times are uncorrelated, there exist strict relations between the cumulants of the
      full counting statistics and the first-passage time distribution. On the other
      hand, when the correlations of the first-passage times are present, their
      distribution may provide additional information about the internal dynamics of
      the system in comparison to the full counting statistics; for example, it may
      reveal the switching between different dynamical states of the system.
      Additionally, I show that breaking of the fluctuation theorem for first-passage
      times may reveal the multicyclic nature of the Markovian network.

PMID- 29448476
TI  - Colloidal particle electrorotation in a nonuniform electric field.
AB  - A model to study the dynamics of colloidal particles in nonuniform electric
      fields is proposed. For an isolated sphere, the conditions and threshold for
      sustained (Quincke) rotation in a linear direct current (dc) field are
      determined. Particle dynamics becomes more complex with increasing electric field
      strength, changing from steady spinning around the particle center to time
      dependent orbiting motion around the minimum field location. Pairs of particles
      exhibit intricate trajectories, which are a combination of translation, due to
      dielectrophoresis, and rotation, due to the Quincke effect. Our model provides a
      basis to study the collective dynamics of many particles in a general electric
      field.

PMID- 29448477
TI  - Stability of a giant connected component in a complex network.
AB  - We analyze the stability of the network's giant connected component under impact
      of adverse events, which we model through the link percolation. Specifically, we
      quantify the extent to which the largest connected component of a network
      consists of the same nodes, regardless of the specific set of deactivated links.
      Our results are intuitive in the case of single-layered systems: the presence of
      large degree nodes in a single-layered network ensures both its robustness and
      stability. In contrast, we find that interdependent networks that are robust to
      adverse events have unstable connected components. Our results bring novel
      insights to the design of resilient network topologies and the reinforcement of
      existing networked systems.

PMID- 29448478
TI  - Effect of risk perception on epidemic spreading in temporal networks.
AB  - Many progresses in the understanding of epidemic spreading models have been
      obtained thanks to numerous modeling efforts and analytical and numerical
      studies, considering host populations with very different structures and
      properties, including complex and temporal interaction networks. Moreover, a
      number of recent studies have started to go beyond the assumption of an absence
      of coupling between the spread of a disease and the structure of the contacts on
      which it unfolds. Models including awareness of the spread have been proposed, to
      mimic possible precautionary measures taken by individuals that decrease their
      risk of infection, but have mostly considered static networks. Here, we adapt
      such a framework to the more realistic case of temporal networks of interactions
      between individuals. We study the resulting model by analytical and numerical
      means on both simple models of temporal networks and empirical time-resolved
      contact data. Analytical results show that the epidemic threshold is not affected
      by the awareness but that the prevalence can be significantly decreased.
      Numerical studies on synthetic temporal networks highlight, however, the presence
      of very strong finite-size effects, resulting in a significant shift of the
      effective epidemic threshold in the presence of risk awareness. For empirical
      contact networks, the awareness mechanism leads as well to a shift in the
      effective threshold and to a strong reduction of the epidemic prevalence.

PMID- 29448479
TI  - Exact solution of a ratchet with switching sawtooth potential.
AB  - We consider the flashing potential ratchet model with general asymmetric
      potential. Using Bloch functions, we derive equations which allow for the
      calculation of both the ratchet's flux and higher moments of distribution for
      rather general potentials. We indicate how to derive the optimal transition rates
      for maximal velocity of the ratchet. We calculate explicitly the exact velocity
      of a ratchet with simple sawtooth potential from the solution of a system of 8
      linear algebraic equations. Using Bloch functions, we derive the equations for
      the ratchet with potentials changing periodically with time. We also consider the
      case of the ratchet with evolution with two different potentials acting for some
      random periods of time.

PMID- 29448480
TI  - Quantum thermodynamics from the nonequilibrium dynamics of open systems: Energy,
      heat capacity, and the third law.
AB  - In a series of papers, we intend to take the perspective of open quantum systems
      and examine from their nonequilibrium dynamics the conditions when the physical
      quantities, their relations, and the laws of thermodynamics become well defined
      and viable for quantum many-body systems. We first describe how an open-system
      nonequilibrium dynamics (ONEq) approach is different from the closed combined
      system +  environment in a global thermal state (CGTs) setup. Only after the open
      system equilibrates will it be amenable to conventional thermodynamics
      descriptions, thus quantum thermodynamics (QTD) comes at the end rather than
      assumed in the beginning. The linkage between the two comes from the reduced
      density matrix of ONEq in that stage having the same form as that of the system
      in the CGTs. We see the open-system approach having the advantage of dealing with
      nonequilibrium processes as many experiments in the near future will call for.
      Because it spells out the conditions of QTD's existence, it can also aid us in
      addressing the basic issues in quantum thermodynamics from first principles in a
      systematic way. We then study one broad class of open quantum systems where the
      full nonequilibrium dynamics can be solved exactly, that of the quantum Brownian
      motion of N strongly coupled harmonic oscillators, interacting strongly with a
      scalar-field environment. In this paper, we focus on the internal energy, heat
      capacity, and the third law. We show for this class of physical models, amongst
      other findings, the extensive property of the internal energy, the positivity of
      the heat capacity, and the validity of the third law from the perspective of the
      behavior of the heat capacity toward zero temperature. These conclusions obtained
      from exact solutions and quantitative analysis clearly disprove claims of
      negative specific heat in such systems and dispel allegations that in such
      systems the validity of the third law of thermodynamics relies on quantum
      entanglement. They are conceptually and factually unrelated issues. Entropy and
      entanglement will be the main theme of our second paper on this subject matter.

PMID- 29448481
TI  - Packing of sedimenting equiaxed dendrites.
AB  - The packing of free-floating crystal grains during solidification has a strong
      impact on the phase-change process as well as on the structure and the defects in
      the solidified material. The packing fraction is affected by the particular
      dendritic morphology of the grains and by their low inertia resulting from the
      small density difference between solid and liquid. Understanding the grain
      packing phenomenon during metal alloy solidification is not experimentally
      possible since packing is coupled to many other phenomena. We therefore
      investigate the packing of equiaxed dendrites on a model system, consisting of
      fixed-shape nonconvex model particles sedimenting in conditions hydrodynamically
      similar to those encountered in solidifying metals. We perform numerical
      simulations by a discrete-element model and experiments with transparent liquids
      in a sedimentation column. The combination of experiments and simulations enables
      us to determine the packing fraction as a function of (i) the grain morphology,
      expressed by a shape parameter, and (ii) the hydrodynamic conditions, expressed
      by the particle Stokes number.

PMID- 29448482
TI  - Phase-coexisting patterns, horizontal segregation, and controlled convection in
      vertically vibrated binary granular mixtures.
AB  - We report patterns consisting of coexistence of synchronous and asynchronous
      states [for example, a granular gas co-existing with (i) bouncing bed, (ii)
      undulatory subharmonic waves, and (iii) Leidenfrost-like states] in experiments
      on vertically vibrated binary granular mixtures in a Hele-Shaw cell. Most
      experiments have been carried out with equimolar binary mixtures of glass and
      steel balls of same diameter by varying the total layer height (F) for a range of
      shaking acceleration (Gamma). All patterns as well as the related phase diagram
      in the (Gamma,F) plane have been reproduced via molecular dynamics simulations of
      the same system. The segregation of heavier and lighter particles along the
      horizontal direction is shown to be the progenitor of such phase-coexisting
      patterns as confirmed in both experiment and simulation. At strong shaking we
      uncover a partial convection state in which a pair of convection rolls is found
      to coexist with a Leidenfrost-like state. The crucial role of the relative number
      density of two species on controlling the buoyancy-driven granular convection is
      demonstrated. The onset of horizontal segregation can be explained in terms of an
      anisotropic diffusion tensor.

PMID- 29448483
TI  - Stochastic and superharmonic stochastic resonances of a confined overdamped
      harmonic oscillator.
AB  - The dynamics of many soft condensed matter and biological systems is affected by
      space limitations, which produce some peculiar effects on the systems' stochastic
      resonance (SR) behavior. In this study, we propose a model where SR can be
      observed: a confined overdamped harmonic oscillator that is subjected to a
      sinusoidal driving force and is under the influence of a multiplicative white
      noise. The output response of the system is a periodic signal with harmonic
      frequencies that are odd multiples of the driving frequency. We verify the
      amplitude resonances at the driving frequencies and superharmonic frequencies
      that are equal to three, five, and seven times the driving frequency, using a
      numerical method based on the stochastic Taylor expansion. The synergistic effect
      of the multiplicative white noise, constant boundaries, and periodic driving
      force that can induce a SR in the output amplitude at the driving and
      superharmonic frequencies is found. The SR phenomenon found in this paper is
      sensitive to the driving amplitude and frequency, inherent potential parameter,
      and boundary width, thus leading to various resonance conditions. Therefore, the
      mechanism found could be beneficial for the characterization of these confined
      systems and could constitute an important tool for controlling their basic
      properties.

PMID- 29448484
TI  - Rolling and aging in temperature-ramp soft adhesion.
AB  - Immediately before adsorption to a horizontal substrate, sinking polymer-coated
      colloids can undergo a complex sequence of landing, jumping, crawling, and
      rolling events. Using video tracking, we studied the soft adhesion to a
      horizontal flat plate of micron-size colloids coated by a controlled molar
      fraction f of the poly(lysine)-grafted-poly(N-isopropylacrylamide) (PLL-g-PNIPAM)
      which is a temperature-sensitive polymer. We ramp the temperature from below to
      above T_{c}=32+/-1^{?}C, at which the PNIPAM polymer undergoes a transition,
      triggering attractive interaction between microparticles and surface. The
      adsorption rate, the effective in-plane (x-y) diffusion constant, and the average
      residence time distribution over z were extracted from the Brownian motion
      records during last seconds before immobilization. Experimental data are
      understood within a rate-equations-based model that includes aging effects and
      includes three populations: the untethered, the rolling, and the arrested
      colloids. We show that preadsorption dynamics casts a characteristic scaling
      function alpha(f) proportional to the number of available PNIPAM patches met by
      soft contact during Brownian rolling. In particular, the increase of in-plane
      diffusivity with increasing f is understood: The stickiest particles have the
      shortest rolling regime prior to arrest, so that their motion is dominated by the
      untethered phase.

PMID- 29448485
TI  - Temperature anisotropy at equilibrium reveals nonlocal entropic contributions to
      interfacial properties.
AB  - Density gradient theory for fluids has played a key role in the study of
      interfacial phenomena for a century. In this work, we revisit its fundamentals by
      examining the vapor-liquid interface of argon, represented by the cut and shifted
      Lennard-Jones fluid. The starting point has traditionally been a Helmholtz energy
      functional using mass densities as arguments. By using rather the internal energy
      as starting point and including the entropy density as an additional argument,
      following thereby the phenomenological approach from classical thermodynamics,
      the extended theory suggests that the configurational part of the temperature has
      different contributions from the parallel and perpendicular directions at the
      interface, even at equilibrium. We find a similar anisotropy by examining the
      configurational temperature in molecular dynamics simulations and obtain a
      qualitative agreement between theory and simulations. The extended theory shows
      that the temperature anisotropy originates in nonlocal entropic contributions,
      which are currently missing from the classical theory. The nonlocal entropic
      contributions discussed in this work are likely to play a role in the description
      of both equilibrium and nonequilibrium properties of interfaces. At equilibrium,
      they influence the temperature- and curvature-dependence of the surface tension.
      Across the vapor-liquid interface of the Lennard Jones fluid, we find that the
      maximum in the temperature anisotropy coincides precisely with the maximum in the
      thermal resistivity relative to the equimolar surface, where the integral of the
      thermal resistivity gives the Kapitza resistance. This links the temperature
      anisotropy at equilibrium to the Kapitza resistance of the vapor-liquid interface
      at nonequilibrium.

PMID- 29448486
TI  - Thermal properties of vortices on curved surfaces.
AB  - We use Monte Carlo simulations to study the finite temperature behavior of
      vortices in the XY model for tangent vector order on curved backgrounds. Contrary
      to naive expectations, we show that the underlying geometry does not affect the
      proliferation of vortices with temperature respect to what is observed on a flat
      surface. Long-range order in these systems is analyzed by using two-point
      correlation functions. As expected, in the case of slightly curved substrates
      these correlations behave similarly to the plane. However, for high curvatures,
      the presence of geometry-induced unbounded vortices at low temperatures produces
      the rapid decay of correlations and an apparent lack of long-range order. Our
      results shed light on the finite-temperature physics of soft-matter systems and
      anisotropic magnets deposited on curved substrates.

PMID- 29448487
TI  - Model for the growth and the oscillation of a cavitation bubble in a spherical
      liquid-filled cavity enclosed in an elastic medium.
AB  - Equations are derived that describe the growth and subsequent damped oscillation
      of a cavitation bubble in a liquid-filled cavity surrounded by an elastic solid.
      It is assumed that the nucleation and the growth of the bubble are caused by an
      initial negative pressure in the cavity. The liquid is treated as viscous and
      compressible. The obtained equations allow one to model, by numerical
      computation, the growth and the oscillation of the bubble in the cavity and the
      oscillation of the cavity surface. It is shown that the equilibrium radius
      reached by the growing bubble decreases when the absolute magnitude of the
      initial negative pressure decreases. It is also found that the natural frequency
      of the bubble oscillation increases with increasing bubble radius. This result is
      of special interest because in an unbounded liquid, the natural frequency of a
      bubble is known to behave oppositely, namely it decreases with increasing bubble
      radius.

PMID- 29448488
TI  - Lee-Yang zeros and large-deviation statistics of a molecular zipper.
AB  - The complex zeros of partition functions were originally investigated by Lee and
      Yang to explain the behavior of condensing gases. Since then, Lee-Yang zeros have
      become a powerful tool to describe phase transitions in interacting systems.
      Today, Lee-Yang zeros are no longer just a theoretical concept; they have been
      determined in recent experiments. In one approach, the Lee-Yang zeros are
      extracted from the high cumulants of thermodynamic observables at finite size.
      Here we employ this method to investigate a phase transition in a molecular
      zipper. From the energy fluctuations in small zippers, we can predict the
      temperature at which a phase transition occurs in the thermodynamic limit. Even
      when the system does not undergo a sharp transition, the Lee-Yang zeros carry
      important information about the large-deviation statistics and its symmetry
      properties. Our work suggests an interesting duality between fluctuations in
      small systems and their phase behavior in the thermodynamic limit. These
      predictions may be tested in future experiments.

PMID- 29448489
TI  - Spontaneous emergence of rogue waves in partially coherent waves: A quantitative
      experimental comparison between hydrodynamics and optics.
AB  - Rogue waves are extreme and rare fluctuations of the wave field that have been
      discussed in many physical systems. Their presence substantially influences the
      statistical properties of a partially coherent wave field, i.e., a wave field
      characterized by a finite band spectrum with random Fourier phases. Their
      understanding is fundamental for the design of ships and offshore platforms. In
      many meteorological conditions waves in the ocean are characterized by the so
      called Joint North Sea Wave Project (JONSWAP) spectrum. Here we compare two
      unique experimental results: the first one has been performed in a 270 m wave
      tank and the other in optical fibers. In both cases, waves characterized by a
      JONSWAP spectrum and random Fourier phases have been launched at the input of the
      experimental device. The quantitative comparison, based on an appropriate scaling
      of the two experiments, shows a very good agreement between the statistics in
      hydrodynamics and optics. Spontaneous emergence of heavy tails in the probability
      density function of the wave amplitude is observed in both systems. The results
      demonstrate the universal features of rogue waves and provide a fundamental and
      explicit bridge between two important fields of research. Numerical simulations
      are also compared with experimental results.

PMID- 29448490
TI  - Capillary network formation from dispersed endothelial cells: Influence of cell
      traction, cell adhesion, and extracellular matrix rigidity.
AB  - The formation of a functional vascular network depends on biological, chemical,
      and physical processes being extremely well coordinated. Among them, the
      mechanical properties of the extracellular matrix and cell adhesion are
      fundamental to achieve a functional network of endothelial cells, able to fully
      cover a required domain. By the use of a Cellular Potts Model and Finite Element
      Method it is shown that there exists a range of values of endothelial traction
      forces, cell-cell adhesion, and matrix rigidities where the network can
      spontaneously be formed, and its properties are characterized. We obtain the
      analytical relation that the minimum traction force required for cell network
      formation must obey. This minimum value for the traction force is approximately
      independent on the considered cell number and cell-cell adhesion. We quantify how
      these two parameters influence the morphology of the resulting networks (size and
      number of meshes).

PMID- 29448491
TI  - Dynamical characterization of transport barriers in nontwist Hamiltonian systems.
AB  - The turnstile provides us a useful tool to describe the flux in twist Hamiltonian
      systems. Thus, its determination allows us to find the areas where the
      trajectories flux through barriers. We show that the mechanism of the turnstile
      can increase the flux in nontwist Hamiltonian systems. A model which captures the
      essence of these systems is the standard nontwist map, introduced by del Castillo
      Negrete and Morrison. For selected parameters of this map, we show that chaotic
      trajectories entering in resonances zones can be explained by turnstiles formed
      by a set of homoclinic points. We argue that for nontwist systems, if the
      heteroclinic points are sufficiently close, they can connect twin-islands chains.
      This provides us a scenario where the trajectories can cross the resonance zones
      and increase the flux. For these cases the escape basin boundaries are
      nontrivial, which demands the use of an appropriate characterization. We applied
      the uncertainty exponent and the entropies of the escape basin boundary in order
      to quantify the degree of unpredictability of the asymptotic trajectories.

PMID- 29448492
TI  - Carbon Quantum Dots as Fluorescent Probes for Imaging and Detecting Free Radicals
      in C. elegans.
AB  - Uniform and hydrophilic carbon quantum dots (C-QDs) were synthesized by
      calcination and NaOH treatment from an organo-templated zeolite precursor. The
      color of luminescence was determined by the concentration of C-QDs. These
      variable-color C-QDs were applied for the first time in the imaging of
      Caenorhabditis elegans (C. elegans) as a model organism. The effects of C-QDs and
      possible behavioral changes in C. elegans were evaluated under treatment
      conditions. We could clearly observe distribution of C-QDs in C. elegans from the
      fluorescence images. Furthermore, we observed significant and detectable
      fluorescence quenching of the C-QDs by free radicals in C. elegans. Our work
      affirms that C-QDs can be developed as imaging probes and as potential
      fluorescent quantitative probes for detecting free radicals.

PMID- 29448493
TI  - Visually Detecting the Variation of miR-301a Expression Using Gold Nanoparticle
      Beacon.
AB  - It is well known that microRNA-301a plays an important role in many diseases, as
      well as is overexpressed in human colon cancer and affects the process of
      tumorigenesis. Determination of the miR-301a expression provides insight into the
      mechanism of tumor progression. In this study, we designed a special hairpin
      deoxyribonucleic acid (DNA) for miR-301a to functionalize gold nanoparticles,
      which served as a beacon for detecting miR-301a expression. A-quenching
      efficiency up to 90% was achieved. The beacon we designed in this study can
      monitor the precise variation of miR-301a expression in vivo. The strategy
      reported in this study is a promising approach for the measurement of miRNA in
      living cells. Moreover, it has a great potential in the study of drug screening
      and discovery.

PMID- 29448494
TI  - Photocatalytic Degradation of Oxytetracycline by Ternary Mixed Catalyst and
      Toxicity Assessment Using Boar Sperm.
AB  - Response surface methodology was adopted to obtain ternary mixed catalysts of
      TiO2-loaded ZSM-5 zeolite and graphene. Oxytetracycline was used as challenged
      toxicant to evaluate the photocatalytic degradation efficiency of the composites.
      The optimal weight ratio of graphene, TiO2, and ZSM-5 was 1:8:1. The composites
      were characterized by ultraviolet-visible spectroscopy, X-ray diffraction,
      fourier transform infrared, N2 adsorption-desorption isotherms, and transmission
      electron microscope with an energy-dispersive spectroscopy system, etc.
      Synthesized samples showed high stability and strong visible-light absorption
      efficiency. The optimal operating conditions of oxytetracycline photocatalytic
      degradation were achieved over a wide range of pH and temperature. With 0.1 g/L
      of optimal ternary mixed composite, the photocatalytic degradation of
      oxytetracycline was nearly reached completion within 150 min at all treatment
      temperatures at pH 7. Toxicity of degraded oxytetracycline solution was assayed
      by a boar sperm quality model using fluorescent staining and flow cytometry.
      During 180 min of photocatalytic treatment, the degraded oxytetracycline solution
      showed increasing biotoxicity and changed the morphology and function of boar
      sperm, despite not killing them.

PMID- 29448495
TI  - A Facile Hydrothermal Synthesis of Three Dimensional Flower-Like NiO-Thermally
      Reduced Graphene Oxide (trGO) Nanocomposite for Selective Determination of
      Dopamine in Presence of Uric Acid and Ascorbic Acid.
AB  - Three dimensional flower-like NiO-thermally reduced Graphene Oxide (trGO)
      nanocomposite was prepared by a simple hydrothermal method. The morphology and
      structure of the nanocomposite was characterized using Scanning Electron
      Microscope (SEM), Transmission Electron Microscope (TEM), Energy Dispersive X-ray
      (EDX), X-ray Diffraction (XRD) and Fourier Transform Infrared (FTIR)
      spectroscopy. The electrocatalytic oxidation of Dopamine, Ascorbic Acid (AA) and
      Uric Acid (UA) was investigated using Cyclic Voltammetry (CV). The modified
      electrode NiO-trGO/GCE showed good electrocatalytic activity compared to bare
      GCE. The detection of dopamine was carried out using Differential Pulse
      Voltammetry (DPV) wherefrom the Limit of Detection (LOD) and linear range was
      estimated to be 50 nM and 10 MUM to 500 MUM respectively. The selective detection
      of dopamine in presence of UA and AA was carried out. The NiO-trGO/GCE showed
      excellent selectivity for the detection of dopamine in presence of UA. However AA
      was found to interfere in the determination of dopamine. Also, the validity of
      the present sensor was examined in human biological samples.

PMID- 29448496
TI  - Mechanical Property of TiO2 Nano-Tubes Surface Based on the Investigation of
      Residual Stress, Tensile Force and Fluid Flow Shear Stress: For Potential
      Application of Cardiovascular Devices.
AB  - The TiO2 nanotube has been anticipated for potential application for
      cardiovascular implanted devices for its excellent drug loading/release function
      and biocompatibility. However, its mechanical behavior has rarely been studied as
      the cardiovascular devices. The tube length is a crucial factor which not only
      decides the drug loading ability but also influences the devices' mechanical
      behavior. Therefore, in this work, the TiO2 nanotubes with different tube length
      (NT2, NT4 and NT6) were fabricated, and their surface energy, residual stress,
      tensile tolerability and blood flow shear stress tolerability were determined,
      respectively. The results showed that there were no significant difference for
      each film samples on surface energy, tensile tolerability and blood flow shear
      stress tolerability, while NT6 obtained the smallest residual stress. These
      results indicated that longer TiO2 nanotubes not only meant loading more drugs
      but also better mechanical properties for surface modification of cardiovascular
      devices.

PMID- 29448497
TI  - Green Electrospining of Hydroxypropyl Cellulose Nanofibres for Drug Delivery
      Applications.
AB  - Electrospun nanofibers mats are green synthesized using hydroxypropyl cellulose
      (HPC) individually or in conjugation with either poly(vinyl alcohol) (PVA) or
      Polyvinylpyrrolidone (PVP) to enhance the mechanical properties of the nanofibers
      mats. Desirable attributes of the as-obtained nanofibers mats are manifested via
      using SEM, FT-IR, TGA and conventional tools for mechanical and physical
      properties. The obtained data from SEM images demonstrated that the diclofenac
      sodium (DS) loaded nanofibers mats did not provide significant change of the
      morphological structure to the mats. In addition the thermal stability and the
      visual and mechanical properties of PVA or PVP was dramatically enhanced with the
      addition of HPC. The in vitro sustained release of DS drug was controlled when
      loaded into electrospun nanofibers of HPC with either PVA or PVP.

PMID- 29448498
TI  - In Vitro Immune Activation of Raw264.7 Cells by Nanodiamonds with Different
      Surface Chemistry.
AB  - In this study, three commercially available nanodiamonds (NDs) of similar size
      (about 5 nm in diameter) but with different surface chemistry (-COOH, -NH2 and 
      poly(ethylene glycol)) were used to study the toxicity and immune activation of
      Raw264.7 cells. Only ND-PEG is well dispersed in water and cell culture medium
      (about 10 nm in diameter), while ND-COOH and ND-NH2 only showed some aggregation,
      about 50 nm in water and about 100 nm in cell culture medium. The three NDs
      showed different zeta potentials in water but the difference disappeared in cell
      culture medium due to the surface adsorption of the proteins. The ND-PEG did not
      show any obvious signs of cytotoxicity or activation on Raw264.7 cells under
      tested conditions. The ND-COOH and ND-NH2 caused dose-dependent toxicity, with
      the amino group capped NDs being much more toxic compare to those of the
      carboxylic acid group at the same exposure conditions. ND-COOH induced a certain
      immune response in Raw264.7 cells, leading to a higher expression of tumor
      necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), especially with a
      significantly longer incubation time. ND-NH2 also induced significant expression
      of TNF-alpha and IL-6 in Raw264.7 cells at first, but this expression was reduced
      with a longer incubation time due to cell death.

PMID- 29448499
TI  - Sol-Gel Derived Antibacterial Ag-Containing ZnO Films on Biomedical Titanium.
AB  - ZnO and Ag-containing ZnO (ZnO/Ag) films with the Ag/Zn molar ratio of 3.3 and
      9.1%, respectively were sol-gel coated on biomedical titanium for antibacterial
      and bioactive surface modification. X-ray diffraction analysis indicates that ZnO
      peaks increase with the calcination temperature of the samples. Scanning electron
      microscopy and energy dispersive of X-ray analyses reveal Ag-rich white particles
      (300~750 nm) on ZnO/Ag samples that were calcined at 400  degrees C. X-ray
      photoelectron spectroscopy analysis of ZnO/Ag samples shows that Zn and O exist
      as ZnO and Ag presents in metallic state. The coating samples exhibit similar UV
      light-induced hydrophilic conversion behavior. Potentiodynamic polarization test
      in a Ca-free Hank's balanced solution demonstrates better corrosion resistance of
      the coating samples compared with the polished sample. In the in vitro
      bioactivity test using the simulated body fluid, a layer of apatite is gradually
      deposited on the surface of sample ZnO/9Ag after 12 days of soaking. The MTT
      assay test shows that ZnO and ZnO/Ag films have weak compatibility with the L929
      cells. The antibacterial test against E. Coli by the disk diffusion assay reveals
      that antibacterial activity of the coating samples increases with silver content
      of the films.

PMID- 29448500
TI  - Morphological Feature of Pluronic F127 and Its Application in Burn Treatment.
AB  - The morphological features of pluronic F127 at various concentrations were
      investigated and 20% aqueous pluronic F127 solution was chosen for the
      preparation of biomembrane. The pluronic solution was mixed with appropriate
      concentration of excipients such as PVA, Povidon S630, PG, Nipagin, Neomycin and
      Panthenol. The prepared pluronic F127 was thermosensitive, a liquid phase at low
      temperatures (<=10  degrees C) but converting into gel at temperatures above 20 
      degrees C, and formed stable biomembrane at 37  degrees C. The neomycin
      impregnated pluronic membrane suppressed the bacterial growth on agar plate by
      the sustained release of neomycin. The histological images of skin tissue after
      applying pluronic gel to burn injured area on rabbit confirmed that the pluronic
      F127 formulation functioned as a matrix to release drug as well as a biomembrane
      to protect burn injury. Thus, the formulated pluronic F127 may have a potential
      for the application of local treatment on burn injury.

PMID- 29448501
TI  - Hydroxyapatite Coatings Containing Mn and Si on the Oxidized Ti-6Al-4V Alloy for
      Dental Applications.
AB  - The purpose of this study was to investigate hydroxyapatite coatings containing
      Mn and Si on the oxidized Ti-6Al-4V alloy for dental applications. Dental implant
      fixture and Ti-6Al-4V ELI disk were used as substrates for plasma electrolytic
      oxidation (PEO) treatment. PEO treatment was performed at 280 V for 3 min in
      various solutions. The surface morphologies of the specimens after PEO treatment
      were observed with a field-emission scanning electron microscope, energy
      dispersive X-ray spectroscopy, X-ray diffractometer, and Fourier transform
      infrared spectroscopy. The breakdown potential for pore formation depended on the
      added ions in electrolytes. Rough surface with micro-pores was formed after
      plasma discharge in the electrolytes containing Si and Mn ions. The surface
      morphologies of implant fixtures were covered with manganese-silicon compounds,
      as Mn concentration increased. From the XRD analysis, anatase peaks decreased, as
      Mn and Si contents increased. From the results of FT-IR analysis, Si-HA and Mn-HA
      was formed on the implant surface.

PMID- 29448502
TI  - In-Vitro Mechanical Performance Study of Biodegradable Polylactic
      Acid/Hydroxyapatite Nanocomposites for Fixation Medical Devices.
AB  - Osteoconductive, biocompatible, and resorbable organic/inorganic composites are
      most commonly used in fixation medical devices, such as suture anchors and
      interference screws, because of their unique physical and chemical properties.
      Generally, studies on biodegradable composites have focused on their mechanical
      properties based on the composition and the individual roles of organic and
      inorganic biomaterials. In this study, we prepared biodegradable
      organic/inorganic nanocomposite materials using the solvent mixing process and
      conventional molding. We used polylactic acid (PLA) as the matrix and nano-sized
      hydroxyapatite (nano-HAp) as the osteoconductive filler. The content of nano-HAp
      was varied in 0-30 wt% and its influence on the In-Vitro mechanical performance
      of PLA/HAp nanocomposites was evaluated. The In-Vitro mechanical properties of
      nanocomposites were evaluated using standardized tensile and flexural tests after
      different immersion times in simulated body fluid.

PMID- 29448503
TI  - Construction and Characterization of Cell-Penetrating Peptide-Fused Fibroblast
      Growth Factor and Vascular Endothelial Growth Factor for an Enhanced Percutaneous
      Delivery System.
AB  - The exogenous administration of growth factors has been examined for treating
      wounds and such factors serve as cosmetic agents for skin regeneration. However,
      the topical application of growth factors is hampered by their limited
      percutaneous absorption. In this study, we genetically modified basic fibroblast
      growth factor (bFGF) and vascular endothelial growth factor-A (VEGF-A) using a
      cell-penetrating peptide to facilitate their permeation into skin and to avoid
      multiple steps in the chemical or physical modification of biomaterials. Low
      molecular-weight protamine (LMWP)-fused bFGF and VEGF-A (LMWP-bFGF and LMWP-VEGF
      A) were designed by serial polymerase chain reaction (PCR)-mediated addition of
      the LMWP codons onto the bFGF and VEGF-A genes and then produced in Escherichia
      coli. The purified LMWP-bFGF and LMWP-VEGF-A represented >90% of the total
      proteins, as determined by SDS-PAGE and densitometric quantification, and their
      actual molecular weights, determined by mass spectroscopy, were 19,026 and 15,715
      Da, respectively, corresponding to the theoretical values. N-terminal amino acid
      sequencing analyses confirmed the N-terminal conjugation of LMWP to bFGF and VEGF
      A. Immunoblotting analyses using antibodies against bFGF and VEGF-A, together
      with the proliferative effects of LMWP-bFGF and LMWP- VEGF-A on human
      keratinocytes and fibroblasts, demonstrated that the original biological activity
      of each growth factor was not altered by LMWP conjugation. In addition, the LMWP
      conjugation did not induce further cytotoxic effects on the skin cells, while the
      cell membrane-penetrating activities of LMWP-bFGF and LMWP-VEGF-A were
      significantly enhanced compared with the respective unconjugated growth factors.
      These results suggest that LMWP-bFGF and LMWP-VEGF-A can be used as effective
      topical therapeutic or cosmetic agents for skin regeneration and anti-aging
      treatments.

PMID- 29448504
TI  - Antifungal Effect of a Dental Tissue Conditioner Containing Nystatin-Loaded
      Alginate Microparticles.
AB  - In this in vitro study, nystatin-alginate microparticles were successfully
      fabricated to control the release of nystatin from a commercial dental tissue
      conditioner. These nystatin-alginate microparticles were spherical and had a
      slightly rough surface. The microparticles incorporated into the tissue
      conditioner were distributed homogeneously throughout the tissue conditioner
      matrix. The incorporation of the microparticles did not deteriorate the
      mechanical properties of the original material. The agar diffusion test results
      showed that the tissue conditioner containing the microparticles had a good
      antifungal effect against Candida albicans. The nystatin-alginate microparticles
      efficiently controlled the release of nystatin from the tissue conditioner matrix
      over the experimental period of 14 days. Moreover, the nystatin-alginate
      microparticles incorporated in the tissue conditioner showed effective antifungal
      function even at lower concentrations of nystatin. The current study suggests
      that the tissue conditioner containing the nystatin-alginate microparticle
      carrier system has potential as an effective antifungal material.

PMID- 29448505
TI  - Novel beta-TCP Coated Titanium Nanofiber Surface for Enhanced Bone Growth.
AB  - In this study, we examined the effect of beta-tricalcium phosphate (beta-TCP)
      coating on alkali-treated CP Grade II titanium surface via RF magnetron
      sputtering on osteoblast like cell (MC3T3-E1) viability and bone formation in rat
      tibia. The specimens were divided into three groups; commercially pure titanium
      (control group), alkali-treated titanium with nanofiber structure (NF group) and
      beta-TCP coating on alkali-treated titanium with nanofiber structure (TNF group).
      The surface characteristics of specimens were observed under a field emission
      scanning electron microscope (FE-SEM), and contact angle was measured. The cell
      viability was assessed in vitro after 1 day, 3 days and 7 days. Implants of 2.0
      mm diameter and 5.0 mm length were inserted into the tibia of rats. After 4 wks,
      the histomorphometric analysis was performed. Group NF and group TNF showed
      improved hydrophilicity of Ti. Group TNF showed significantly higher cell
      viability (P < 0.05) after 7 days. The bone to implant contact (BIC) ratio of the
      control group, NF group, and TNF group were 32.3%, 35.5%, and 63.9%,
      respectively. The study results suggested that beta-TCP coated alkali-treated
      titanium surface via RF magnetron sputtering might be effective in implant
      dentistry due to enhanced hydrophilicity, improved cell response, and better
      osseointegration.

PMID- 29448506
TI  - Polylactic Acid/Nanostructured Si-Substituted beta-Tricalcium Phosphate
      Composites for Biodegradable Fixation Medical Devices.
AB  - Organic/inorganic biocomposite materials for biodegradable fixation medical
      devices require osteoconductivity, biocompatibility, and adequate mechanical
      properties with biodegradation behavior. The objective of this study was to
      investigate the effect of Si ions substituted in beta-tricalcium phosphate (beta
      TCP) on the mechanical properties of organic/inorganic biocomposites.
      Biodegradable composite materials were prepared with polylactic acid (PLA) as the
      matrix and nano Si-substituted beta-TCP as the osteoconductive filler by solvent
      mixing and conventional molding. The nanostructured Si-substituted beta-TCP
      powders were synthesized by co-precipitation, controlling the quantity of Si
      ions. The amount of nanostructured Si-substituted beta-TCP powders in composites
      was varied in the 0-40 wt% range and the material properties were compared with
      those of pure beta-TCP/PLA composites. The influence of Si ions on the mechanical
      properties of the composites was evaluated by tensile and flexural tests.

PMID- 29448507
TI  - Platinum Nanoparticles Induce Apoptosis on Raw 264.7 Macrophage Cells.
AB  - The cellular effects of platinum nanoparticles (PNP05, average size of 5 nm, and
      PNP30, average size of 30 nm) were investigated on murine leukemia Raw 264.7
      cells. Cells treated with various concentrations of PNPs showed size-dependent
      cytotoxicity in an MTT assay with PNP5 of smaller nanoparticles higher toxicity
      than PNP30. Investigations on cell morphology, Annexin V assay, DNA fragmentation
      and the activity of caspase-3/-7 showed that PNPs induced apoptosis on Raw 264.7
      cells by changing cell morphology and density, increasing cell population in
      apoptosis and causing nucleus fragmentation. Further study on caspase activity by
      Western blotting revealed that the apoptosis was induced by the activation of
      caspase-3 and -7. In addition, PNPs inactivated DNA repair system, generating
      dose-dependent DNA ladder bands on agarose gel electrophoresis. Taken together,
      PNPs triggered cytotoxicity on Raw 264.7 cells by suppressing cell
      growth/survival and inducing apoptosis.

PMID- 29448508
TI  - In Vivo; In Vitro Interaction of Silver Nanoparticles with Leucine Aminopeptidase
      from Human and Plasmodium falciparum.
AB  - There is increasing requirement for the development of new drug protocols against
      malaria, a fatal disease caused by the lethal parasite Plasmodium falciparum.
      Leucine aminopeptidase (Pf LAP) of Plasmodium falciparum, is being pursued as a
      promising target for the discovery of novel antimalarials. The effects of silver
      nanoparticles (AgNPs) against P. falciparum leucine amino-peptidase (Pf LAP) and
      the human homolog (HsLAP) were compared. Pf LAP and HsLAP were expressed in
      Escherichia coli, and AgNPs (3-10 nm) characterized by ultra-violet spectroscopy
      and transmission electron microscopy. Pf LAP indicated a Km of 694 MUM towards
      leucine-p-nitroanilide and a Vmax of 57.9 MUmol.ml-1 . min-1 while HsLAP had a Km
      of 1.6 mM and Vmax of 119.6 MUmol . ml-1 . min-1. On interaction with AgNPs (670
      nM) Pf LAP was selectively inhibited (57.1%; Ki = 610 nM) relative to HsLAP
      (10.8%; Ki = 5.22 MUM). Structural differences between the enzyme variants,
      particularly the orientation and distance of surface Met349 in Pf LAP and Met306
      in HsLAP to the zinc binding sites were significant and may allow for selective
      targeting of Pf LAP by AgNPs. The viability of P. falciparum parasites was
      decreased when exposed to silver nanoparticles, with an IC50 value of 6.96 MUM,
      compared to an IC50 value of 647.7 MUM for human HeLa cells.

PMID- 29448509
TI  - Nicotinic Acid Coated Magnetite Nanorods Evaluation by Lipid Profile Analysis and
      Genetic Tests.
AB  - In our present work some biological tests were carried out to assess the
      biocompatibility of nicotinic acid coated magnetite nanorods. Pure and coated
      nanorods were injected intraperitoneally to cholesterol fed mice with dose values
      of 25, 50 mg/Kg. Investigations were done on treated mice with/without exposure
      to low frequency electromagnetic field (EMF) and samples were collected fourteen
      days post treatment. Toxicological effects were evaluated using Micronucleus and
      DNA fragmentation analysis. The results indicated that low dose (25 mg/Kg)
      nicotinic acid coated nanorods had insignificant toxicological effects in
      comparison to that of control group. Lipid profile analysis and gene expression
      of atheroprotective (eNOS) and atherogenic (p65) genes were also investigated. It
      was found that experimental groups treated with low dose nicotinic acid coated
      magnetite nanorods and exposed to EMF showed interesting alterations in mice
      lipid profile. As a result, an insignificant but slight increase in gene
      expression levels of eNOS and a significant decrease in p65 gene expression were
      observed. Our study suggests that our proposed magnetic nanosystem in combination
      with EMF has good biocompatibility and can be a potential drug precursor with
      therapeutic values.

PMID- 29448510
TI  - Preparation and In Vivo Biodistribution of Ultra-Small Superparamagnetic Iron
      Oxide Nanoparticles with High Magnetic Targeting Response.
AB  - The ultra-small superparamagnetic iron oxide (USPIO) particles with high
      saturation magnetization and good superparamagnetism were prepared by reverse
      micro-emulsions using novel C16E15 as surfactant, which can reduce magnetic
      dipole-dipole interaction, hence decreasing the critical blocking temperature
      (TB). Powder X-ray diffraction (XRD), Infrared spectrum (FT-IR), Transmission
      electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), and Vibrating
      sample magnetometer (VSM) were used to characterize the magnetic particles. The
      higher ratio of Fe2+/Fe3+ caused redundant FeO on the USPIO surface. An in vitro
      approach model for simulating target delivery of USPIO particles to sites of
      interest was developed to illustrate the relationship between magnetic fluid
      retention rate and pole distance. In Vivo targeted interception and magnetic
      targeting bio-distribution of superparamagnetic particles were also investigated
      simultaneously. The results indicated that the USPIO had high ability for
      magnetic focusing in mimetic surrounding tissue surrounding blood vessels under
      the action of pulsed magnetic field. The USPIO nanoparticles will be fundamental
      in biomedical applications.

PMID- 29448511
TI  - Preparation and In Vitro Evaluation of Elastic Nanoliposomes for Topical Delivery
      of Highly Skin-Permeable Growth Factors.
AB  - Percutaneous delivery of growth factors is often used to treat wounds, and for
      cosmetic purposes, as a way of accelerating healing and skin regeneration,
      respectively. However, the therapeutic effects of growth factors are diminished
      by their poor absorption when delivered percutaneously, in addition to their
      rapid degradation by proteinases. To overcome these obstacles, we constructed two
      skin-permeable compounds. Basic fibroblast growth factor (bFGF) and vascular
      endothelial growth factor-A (VEGF-A) were both genetically paired with low
      molecular-weight protamine (LMWP), to yield the compounds LMWP-bFGF and LMWP-VEGF
      A, respectively. The molecular weights and N-terminal amino acid sequences of
      LMWP-bFGF and LMWP-VEGF-A confirmed that the N-terminus-specific conjugation of
      LMWP with bFGF and VEGF-A had been successful. The biological abilities of the
      native factors to stimulate human fibroblast (CCD-986sk) and endothelial cell
      proliferation were preserved. Both compounds significantly promoted wound
      (scratch) recovery and enhanced procollagen type I C-peptide synthesis in CCD
      986sk cells (to levels 184 and 133% those of the native compounds, respectively).
      The LMWP-conjugated growth factors were significantly more permeable than the
      native forms (by 7.29- and 29.22-fold, respectively). Finally, encapsulation of
      the compounds in positively charged elastic nanoliposomes (115 +/- 1.54 nm in
      diameter with a zeta potential of 57.2 +/- 3.05 mV) further improved both
      permeation and stability. Thus, nanoliposomes loaded with LMWP-conjugated growth
      factors are expected to enhance skin regeneration; the materials will find
      applications in wound-healing therapies and anti-wrinkle cosmetics.

PMID- 29448512
TI  - Thymosin beta4 Reduces H2O2 Induced Oxidative Stress in MC3T3-E1 Cells on
      Titanium Surface.
AB  - Thymosin beta4 (Tbeta4) is known to inhibit an inflammatory response and to
      increase the survival of osteoblasts on titanium (Ti) surfaces. Ti is the most
      widely used graft material in dentistry; however, an inflammatory response
      induced following implant placement results in the generation of reactive oxygen
      species (ROS). The oxidative stress from the production of ROS such as nitric
      oxide (NO) and hydrogen peroxide (H2O2) can damage surrounding cells, resulting
      in implant failure by decreasing cell viability. Thus, the aim of this study was
      to determine the biological effects of Tbeta4 on the oxidative stress induced to
      MC3T3-E1 preosteoblasts on the Ti surface. Based on an MTT assay and
      bromodeoxyuridine immunofluorescence staining, Tbeta4 was found to increase the
      proliferation of the H2O2-exposed MC3T3-E1 cells on Ti discs. Reverse
      transcription-polymerase chain reaction and western blot analyses showed that
      Tbeta4 decreased the mRNA and protein expression levels of inducible nitric oxide
      synthase (iNOS) and cyclooxygenase-2 (COX-2) in H2O2-exposed MC3T3-E1 cells on
      the Ti discs. Tbeta4 inhibited the synthesis of intracellular ROS and the
      secretion of NO and prostaglandin E2 (PGE2) from H2O2-exposed MC3T3-E1 cells on
      the Ti discs. In conclusion, Tbeta4 inhibits H2O2-induced iNOS and COX-2
      expression with a decrease in ROS, NO, and PGE2 synthesis, which leads to
      improved cell survival with low cytotoxicity under an oxidative stress condition
      in MC3T3-E1 cells on the Ti surface. This suggests that Tbeta4 may be a crucial
      molecule to reduce oxidative stress-induced cell damage or hypoxia, leading to
      promoted osseointegration on the Ti surface during implant placement.

PMID- 29448514
TI  - Facile One-Pot Synthesis of Graphene Oxide by Sonication Assisted Mechanochemical
      Approach and Its Surface Chemistry.
AB  - Facile one pot synthesis of graphene oxide (GO) by sonication assisted
      mechanochemical approach has been reported here. The amalgamation of
      ultrasonication and mechanical stirring has assisted the synthesis of GO in a
      short time duration of only 4 hours with good reaction yield. The structural
      characterization of GO was performed by X-ray diffraction spectroscopy (XRD),
      Fourier transform infrared spectroscopy (FTIR), UV-Visible spectroscopy and Raman
      spectroscopy. Atomic force microscopic (AFM) analysis manifested the flake like
      morphology of GO with average sheet thickness ~1.5 nm. AFM also provides
      important information about the surface roughness. Transmission electron
      microscope (TEM) analysis gave clear visualization of well exfoliated structure
      of GO in the form of thin flakes. The field emission scanning electron microscope
      (FESEM) analysis revealed a crimpling surface morphology of GO. The average size
      of GO flake as revealed through various morphological as well as light scattering
      techniques was around 3 MUm. Moreover, important surface chemistry of the
      synthesized GO was well ascertained through contact angle analysis, AFM analysis
      and zeta potential analysis.

PMID- 29448513
TI  - Removing Control of Cyclodextrin-Drug Complexes Using High Affinity Molecule.
AB  - Nanostructured supramolecular assemblies with hydrophobic cavities are used for
      improving the solubility, bioavailability, and stability of poorly water soluble
      drugs. In particular, host-guest inclusion using 2-hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) is a typical approach in the pharmaceutical field. In
      this study, celecoxib (CXB), a cyclooxygenase-2 selective nonsteroidal anti
      inflammatory drug (NSAID), was used as the model drug (guest material) and
      effectively incorporated into HP-beta-CD (host material). After forming a
      complete complex of HP-beta-CD and CXB, 1-adamantylamine (ADA) was used to allow
      CXB to be released from the HP-beta-CD in a concentration-dependent manner. This
      was revealed from Fourier-transform infrared spectroscopy and drug dissolution
      studies. Notably, the use of ADA, which is a high-affinity guest molecule, with
      cyclodextrin accelerated the removal of CXB from the host material through the
      exchange of guest molecules. Taken together, the host-guest based approach using
      a second guest molecule is useful for regulating on-demand drug release and could
      therefore be a potential tool for biomedical applications.

PMID- 29448515
TI  - Polyalkylene Glycol Based Lubricants and Tribological Behaviour: Role of Ionic
      Liquids and Graphene Oxide as Additives.
AB  - The polyalkylene glycol (PAG) lubricants are widely used as gear, bearing and
      compressor oils in refrigerant systems. They are designed to provide outstanding
      benefits in terms of efficiency, long oil life, and equipment protection. These
      fully synthetic lubricants have been developed for use under operating conditions
      beyond the capabilities of other synthetic lubricants and mineral oils as their
      characteristic low pour point ensures excellent fluidity at low-temperature. On
      the other hand, the main drawback of PAG oils is the marked hygroscopicity, i.e.,
      they absorb and bind moisture from the ambient air. In this paper, the results
      from tribological testing of PAG oil featuring 46 cSt at 40  degrees C with solid
      (graphene oxide) and liquid (ionic liquids) additives are discussed. Moreover, in
      this study the influence of absorbed moisture from ambient air has been
      investigated. Preliminary experiments with ball-on-flat setup by using
      reciprocatory tribometer tested the response of base oil PAG 46 blended with 1
      Ethyl-3-methylimidazolium acetate or graphene oxide, alternatively. In such a
      way, the individual influence of each additive was questioned. Based on
      preliminary analysis, this research focuses on hybrid formulations to
      substantiate potential improvements of anti-friction and anti-wear PAG 46
      performance over broad range of lubrication regimes. Experimental tests have been
      carried out by using rotational disc tribometer in ball-on-disc configuration.
      Additional experiments after samples exposure to ambient air and ensuing moisture
      absorption were carried out. The results highlight that in most cases limited
      absorbed moisture does not introduce detrimental effects on the tribological
      performances of the tested oil samples: indeed, water content could reduce wear
      of the sliding steel surfaces over the whole testing spectrum and in most of the
      cases the frictional energy dissipation.

PMID- 29448516
TI  - Mesoporous Ga-TiO2: Role of Oxygen Vacancies for the Photocatalytic Degradation
      Under Visible Light.
AB  - Gallium doped mesoporous TiO2 with different weight percentages were synthesized
      by sol-gel method using Pluronic P123 as the structure directing template. The
      physico-chemical properties of all the synthesized catalysts were determined by
      XRD, TEM, SEM-EDAX, N2 adsorption-desorption studies, XPS, UV-vis DRS, FT-IR and
      photoluminescence spectroscopy. 1.0 wt% Ga-TiO2 exhibited the highest
      photocatalytic efficiency among all the synthesized materials under visible light
      due to the high surface area, reduced band gap and suppressed electron-hole
      recombination. Ga3+ ions substitutions for Ti4+ ions in TiO2 lattice created
      oxygen vacancies in TiO2 lattice, which created a defect energy level below the
      conduction band of TiO2 and hence the band gap was reduced. The oxygen vacancy
      defects was playing significant role to improve the adsorption of oxygen
      molecules, hydroxide ions and cationic rhodamine B (RhB) on TiO2 surface in an
      aqueous medium. The lifetime of the charge carriers was also enhanced by trapping
      the photogenerated electrons in oxygen vacancies and transferring them to the
      adsorbed O2 to produce superoxide anion radicals (O-. 2 ). The photo-induced
      holes at valence band reduced the adsorbed OH- ions and produced a large number
      of .OH radicals, which subsequently degraded the RhB. Hence oxygen vacancies
      created by gallium doping on TiO2 enhanced the photocatalytic efficiency for the
      degradation of RhB under visible light.

PMID- 29448517
TI  - Thermal and Mechanical Characterization of Polymeric Foams with Controlled
      Porosity Using Hollow Thermoplastic Spheres.
AB  - Polyurethane (PU) foams with controlled porosity and pore structure are prepared
      via judicious study on expanding process parameters for thermoplastic expandable
      microspheres which are compatible with PU synthetic process. Thermal and
      mechanical properties of PU foams are found to be generally governed by amount of
      the porosity. Thermal conductivity of PU foams with controlled porosity is
      measured at 30  degrees C with transient hot bridge method. The measured thermal
      conductivity of PU foams is estimated using theoretical models, proving the
      formation of spherical pore structures of expandable microspheres in PU matrix
      and serving as an internal porous material.

PMID- 29448518
TI  - Effect of Aspect Ratio on Electrical, Rheological and Glass Transition Properties
      of PC/MWCNT Nanocomposites.
AB  - Since the discovery of carbon nanotubes (CNT), significant research works have
      focused on the application of CNT as conductive filler to polymer nanocomposites
      which can be used in several fields such as electrostatic dissipation (ESD),
      electrostatic painting and electromagnetic interference shielding (EMI
      shielding). However, the main challenge in the large-scale manufacturing of this
      technology is the poor electrical conductivity of polymer nanocomposites produced
      by injection molding process. This study aims to investigate the effect of CNT
      aspect ratio in improving the electrical conductivity of injection molded
      nanocomposites. In this work, three types of multiwall carbon nanotubes with
      different lengths were melt-mixed with polycarbonate in a twin screw extruder
      followed by injection and compression molding. Results show that nanocomposites
      with higher CNT aspect ratio exhibit higher electrical conductivity. Longer
      nanotubes form a stronger conductive network during secondary agglomeration which
      can withstand the high shear forces during injection molding. Higher melt
      viscosity and storage modulus were observed in nanocomposites with higher CNT
      aspect ratio which is attributed to the effective constriction of polymer chains
      by longer nanotubes. It was also found that Tg of the composites increased with
      nanotube aspect ratio and the addition of CNT causes degradation which leads to
      the general Tg depression of polycarbonate.

PMID- 29448519
TI  - Peroxidase-Like Activity of Gold Nanoparticles and Their Gold Staining Enhanced
      ELISA Application.
AB  - We found that the peroxidase-like activity of gold nanoparticles (GNPs) followed
      the Michaelis-Menten kinetic model and was dependent on environmental pH and
      temperature, which was very similar to natural Horseradish Peroxidase (HRP).
      However, unlike HRP, which needs a lower H2O2 concentration with a very narrow
      range to reach a maximum reaction rate and avoid enzyme poisoning, GNPs have very
      high activity, even at an H2O2 concentration two orders of magnitude higher than
      HRP. It was demonstrated that H2O2 treatment could enhance the peroxidase-like
      activity of GNPs, resulting thus in the activity increase in a circular catalytic
      reaction by the reduplicative use of GNPs. It was also found that the peroxidase
      like activity of GNPs responded sensitively to nanoparticle size and surface
      modifications. When used in an immunoassay, GNPs were generally conjugated with
      antibody and blocked with hydrophilic macromolecules to construct a nanoprobe.
      This strongly reduced the peroxidase-like activity and detection sensitivity of
      GNPs, therefore, restricting their use as peroxidase mimetics. We presented a
      novel strategy that combined the nanoprobes with gold staining to expose fresh
      catalytic gold surfaces and obtained a great increase in detection sensitivity.

PMID- 29448520
TI  - Synthesis of Fluorophore Decorated Single-Walled Carbon Nanotubes for In-Vitro
      Cytocompatibility.
AB  - We report rhodamine based fluorophore derivative for the stable dispersion of
      single-walled carbon nanotubes (SWCNTs), which can afford better fluorescent
      label to carbon nanotubes (CNTs). The nanotubes-fluorophore conjugates are
      helpful in achieving stable dispersion in polar and non-polar solvents with
      intense fluorescence. The product was characterized through NMR, Mass
      spectrometry, Raman, XPS, SEM, AFM and Fluorescence measurements. The formation
      of SWCNT-g- Rhodamine was confirmed by the presence of D and G bands in Raman
      spectrum. The alkyl and aryl groups in the range of 14.8, 17.6, 38.1 and 96.3 ppm
      confirms the grafting of the nanocomposite through NMR. The morphological studies
      were carried out intensively for analyzing SWCNTs stable dispersion and the
      results from EDAX measurements shows the elements weight% of C: 35.09 and N: 30.1
      concludes that SWCNTs are completely grafted onto rhodamine derivatives. The
      application of SWCNTs fluorophore conjugates were analyzed by cell viability
      studies using MTT assay and exhibits less toxic compare to other functionalized
      CNTs. The viability of percentage increases with decrease in the concentration of
      SWCNT-COCl with 91.7% of live cells even after 24 h at a concentration of 250 MUg
      for SWCNT-g-Rhodamine. The fluorescent images obtained during viability analysis
      shows enhanced fluorescence for living cells in case of SWCNT-g-Rhodamine
      compared to SWCNT-COCl, which clearly shows the utility of decorating nanotubes
      with fluorophore. This research work further extends its application for
      molecular sensing and other biological process.

PMID- 29448521
TI  - Effect of Ammonium Salts on the Hydrothermal Synthesis of TiO2 Nanocubes for Dye
      Sensitized Solar Cells.
AB  - TiO2 nanocubes were synthesized via hydrolysis condensation of titanium tetra
      isopropoxide (TTIP) in aqueous media, followed by hydrothermal treatment with
      ammonium salts. Various ammonium salts with different alkyl chain such as
      ammonium hydroxide (NH4OH), tetramethylammonium hydroxide (TMAH),
      tetraethylammonium hydroxide (TEAH) and tetrabutylammonium hydroxide (TBAH) were
      investigated. The crystalline phase, shape, and morphology of TiO2 nanocubes were
      studied by XRD, TEM, and SEM analysis. These TiO2 nanocubes were pure anatase
      phase and tended to assemble with well-ordered and close-packed domains. Both
      alkyl chain length of ammonium salts and hydrothermal duration affected the TiO2
      nanocube formation process. The ammonium salts with longer alkyl chain formed
      TiO2 nanocubes in shorter hydrothermal time and offered the smallest particle
      size. The above TiO2 nanocubes were applied as photoanode materials in N719
      anchored dye-sensitized solar cells and one of the cells exhibited the maximum
      power conversion efficiency of 7.85%.

PMID- 29448522
TI  - Effect of Graphene/TiO2 Composite Layer on the Performance of Dye-Sensitized
      Solar Cells.
AB  - Graphene has attracted a lot of attention because of its unique mechanical,
      thermal, electrical and optical properties. In this study, a double layered
      structured photoanode consisting of a graphene/TiO2 composite layer and a TiO2
      nanoparticles (P25) underlayer was developed. The photoelectric properties of as
      prepared double layer structured photoanode were studied with comparison of the
      anatase TiO2 photoanode. Graphene was prepared by reduction of graphene oxide
      (GO) under a hydrothermal conditions and graphenen/TiO2 composite semiconductor
      materials were prepared by mixing graphene into TiO2 paste. The effect of
      graphene contents in graphene/TiO2 composite layer was also investigated. After
      constructing double layer photoanode with proper amount of graphene, the
      photoanode displayed enhanced light and dye adsorption properties with higher
      light harvesting efficiency, lower internal resistances, faster electron
      transport and lower charge recombination rate, which resulted in high current
      density. At the optimum conditions, the DSSC exhibited a Jsc of 15.01 mA cm-2, a
      Voc of 0.72 V, and a FF of 0.66 with the energy conversion efficiency (eta) of
      7.08%, indicating a increase in Jsc and eta respectively than that of DSSC based
      on pure TiO2 photoanode, which gives a Jsc of 13.25 mA cm-2, a Voc of 0.73 V, and
      a FF of 0.62 with a eta of 5.94%. However, the addition of excess graphene in the
      composite layer led to the enhancement of charge recombination, the reduction of
      dye adsorption and the decrease of photoelectric conversion efficiency of DSSCs.
      The graphene/TiO2 composite layer in DSSCs could really enhance its efficiency
      after the amount of graphene was successfully optimized.

PMID- 29448523
TI  - Mimicking the Synaptic Weights and Human Forgetting Curve Using Hydrothermally
      Grown Nanostructured CuO Memristor Device.
AB  - In the present investigation, we have fabricated copper oxide (CuO) thin film
      memristor by employing a hydrothermal method for neuromorphic application. The X
      ray diffraction pattern confirms the films are polycrystalline in nature with the
      monoclinic crystal structure. The developed devices show analog memory and
      synaptic property similar to biological neuron. The size dependent synaptic
      behavior is investigated for as-prepared and annealed CuO memristor. The results
      suggested that the magnitude of synaptic weights and resistive switching voltages
      are dependent on the thickness of the active layer. Synaptic weights are improved
      in the case of the as-prepared device whereas they are inferior for annealed CuO
      memristor. The rectifying property similar to a biological neuron is observed
      only for the as-prepared device, which suggested that as-prepared devices have
      better computational and learning capabilities than annealed CuO memristor.
      Moreover, the retention loss of the CuO memristor is in good agreement with the
      forgetting curve of human memory. The results suggested that hydrothermally grown
      CuO thin film memristor is a potential candidate for the neuromorphic device
      development.

PMID- 29448524
TI  - Effects of Electrode Thickness on Three-Dimensional NiCrAl Metal Foam Cathode for
      Lithium Ion Battery.
AB  - LiFePO4 electrodes using three dimensional NiCrAl alloy metal foam of different
      electrode thickness are prepared. In order to improve the electrochemical and
      cycle-life performance of lithium ion batteries, it is important to optimize the
      electrode thickness and mass loading of active material. As compared to those
      with thick electrode, the cells with thin electrode exhibit high rate performance
      and cycle-life behavior, due to the shorter diffusion length of lithium-ion and
      improved kinetic behavior. Also, cyclic voltammetry curves and electrochemical
      impedance spectroscopy analysis indicate that the redox reaction for the thinner
      electrode occurs much faster, and the charge transfer resistance is much lower.
      The results of same current density (mA cm-2) show that 450 MUm-thickness
      electrode exhibits superior electrochemical and power performance. It is because
      the 300 MUm-thickness electrode which has the lowest mass loading of active
      material meant that it carried the highest current rate, and thicker electrodes
      show higher internal resistance and much poorer kinetic property. Namely,
      electrode thickness and an amount of active material are difference according to
      the intended use.

PMID- 29448525
TI  - Zn2SnO4-Reduced Graphene Oxide Nanohybrids for Visible-Light-Driven
      Photocatalysis.
AB  - Zn2SnO4-reduced graphene oxide photocatalysts were synthesized by using SnCl4
      5H2O, Zn(NO3)2 . 6H2O and graphene oxide via hydrothermal process. The structure,
      morphology, specific surface area and photo response of the as-prepared
      nanocomposites were characterized by X-ray diffraction, Transmission electron
      microscopy, UV-vis diffuse reflectance spectra, Brunauer-emmett-teller surface
      area measurement and Photoluminescence emission spectra. Experimental results
      showed that the Zn2SnO4 nanoparticles, with 20-30 nm a size range, were uniformly
      dispersed on the surfaces of reduced graphene oxide. Moreover, the as-prepared
      Zn2SnO4-reduced graphene oxide photocatalysts exhibited enhanced photocatalytic
      activities for degradation of Rhodamine B compared to those of pure Zn2SnO4. When
      the amount of reduced graphene oxide was 4 wt%, it showed the highest
      photocatalytic efficiency of 99.7% for 240 min, and the photocatalytic efficiency
      was still 98.5% after it was recycled 4 times. It also possessed the band gap of
      2.48 eV and specific surface area of 58.1 m2 g-1.

PMID- 29448526
TI  - Physico-Chemical, Electrochemical and Structural Insights Into Poly(3,4
      ethylenedioxythiophene) Grafted from Molecularly Engineered Multi-Walled Carbon
      Nanotube Surfaces.
AB  - Composites of multi-walled carbon nanotubes (MWCNTs) and poly(3,4
      ethylenedioxythiophene) (PEDOT) are attracting the attention of material
      scientists since more than a decade as potential next-generation optoelectronic
      materials for their peculiar features, arising from the combination of the
      intrinsic electrical, thermal and morphological properties of the two components.
      They are indeed a promising platform for the development of low-cost, portable
      and environmentally friendly electronic devices such as supercapacitors, sensors
      and actuators. Here a novel synthetic strategy for their preparation is
      envisaged, exploiting the possibility to covalently functionalize the external
      surface of MWCNTs with tailored molecular units, starting from which the growth
      of the conjugated polymer can be induced oxidatively. The approach demonstrates
      its value in being able to effectively promote the formation of PEDOT chains in
      direct contact with the surface of MWCNTs, differently from what results when the
      monomer is polymerized in the presence of the pristine carbon nanomaterial. In
      addition, significant differences are found in the physico-chemical properties
      and electrochemical behavior when MWCNT-PEDOT covalent composites are studied in
      comparison to a non-covalent analogue, here illustrated in detail. These
      evidences constitute a starting point for the future development of novel more
      finely tuned functional materials based on MWCNT-PEDOT composites, featuring the
      required optoelectronic properties to precisely target the desired application.

PMID- 29448527
TI  - Novel Synthesis and Characterization Studies of Spinel Nix Co1-x Al2O4 (x = 0.0
      to 1.0) Nano-Catalysts for the Catalytic Oxidation of Benzyl Alcohol.
AB  - Ni-doped cobalt aluminate NixCo1-xAl2O4 (x = 0.0, 0.2, 0.4, 0.6, 0.8 and 1.0)
      spinel nanoparticles were successfully synthesized by a simple microwave
      combustion method using urea as the fuel and as well as reducing agent. X-ray
      powder diffraction (XRD) was confirmed the formation of single phase, cubic
      spinel cobalt-nickel aluminate structure without any other impurities. Average
      crystallite sizes of the samples were found to be in the range of 18.93 nm to
      21.47 nm by Scherrer's formula. Fourier transform infrared (FT-IR) spectral
      analysis was confirmed the corresponding functional groups of the M-O, Al-O and M
      Al-O (M = Co and Ni) bonds of spinel NixCo1-xAl2O4 structure. Scanning electron
      microscope (SEM) and transmission electron microscope (TEM) images was confirmed
      the particle like nanostructured morphology. Energy band gap (Eg) value was
      calculated using UV-Visible diffuse reflectance spectra (DRS) and the Eg values
      increased with increasing Ni2+ dopant from x = 0.2 (3.58 eV) to x = 1.0 (4.15
      eV). Vibrating sample magnetometer (VSM) measurements exposed that undoped and Ni
      doped CoAl2O4 samples have superparamagnetic behavior and the magnetization (Ms)
      values were increased with increasing Ni2+ ions. Spinel NixCo1-xAl2O4 samples has
      been used for the catalytic oxidation of benzyl alcohol into benzaldehyde and was
      found that the sample Ni0.6Co0.4Al2O4 showed higher conversion 94.37% with 100%
      selectivity than other samples, which may be due to the smaller particle size and
      higher surface area.

PMID- 29448528
TI  - Removal of Waterborne Pathogen by Nanomaterial-Membrane Coupling System.
AB  - The waterborne pathogenic viruses threaten human health. And the nanomaterial
      membrane coupling system is promising in virus removal. In this study, phage MS2
      was selected as the model virus to investigate the removal of virus with the
      coupling system. Results revealed that commercial nano TiO2 (Degussa Aeroxide
      P25) showed both of excellent adsorption and photocatalysis performance for virus
      removal compared with nano ZnO, nano Fe3O4, carbon nanotube, graphene, nano Ni
      and Nano TiO2 (anatase). In P25 photocatalysis process, the removal efficiency of
      phage MS2 increased with the increase of P25 concentration (0~1000 mg L-1), virus
      initial concentration (102~106 PFU mL-1), UV irradiation doses (5~120 mJ cm-2)
      and UV light intensity (0.126~0.742 mW cm-2). However, when the P25 concentration
      increased to over 1000 mg L-1, the virus removal efficiency would remain stable
      with the increase of P25 concentration. The nanomaterial-membrane coupling system
      showed excellent performance for virus removal, which was mainly attributed to
      the adsorption and photocatalysis of P25, and the intercept of membrane. When the
      P25 concentration was 100 mg L-1, UV irradiation dose was 20 mJ cm-2 and
      transmembrane pressure was 20 kPa, the phage MS2 removal efficiency could be up
      to 100%.

PMID- 29448529
TI  - Improved Adsorption Performance of alpha-Fe2O3 Modified with Carbon Spheres for
      Cr(VI) Removal from Aqueous Solution.
AB  - Carbons spheres, easily fabricated by glucose hydrolysis, were integrated with
      alpha-Fe2O3 for removing heavy metal from contaminated water. The alpha-Fe2O3
      particles were anchored on the surface of carbon spheres and the combination of
      two components provided more rough surface area, enhancing the adsorption
      performance of alpha-Fe2O3. The removal efficiency of Cr(VI) on alpha
      Fe2O3/carbon spheres was 88% in 240 min, which was 1.93 times higher than that of
      pristine alpha-Fe2O3. The investigation on adsorption kinetics and isotherm
      showed that the pseudo-first-order kinetic and Langmuir isotherm models could
      well fit the experimental data. The adsorption rate was mainly controlled by both
      exterior and interior surface diffusion steps. Adsorption thermodynamics
      investigation proved that the Cr(VI) adsorption on alpha-Fe2O3/carbon spheres was
      an endothermic (93.32 kJ . mol-1) and spontaneous (-3.96 kJ . mol-1) physical
      process. The adsorption capacity was 18.7 mg . g-1 and after recycling five
      times, the decline of adsorption capacity of alpha-Fe2O3/carbon spheres was 7.8%,
      which indicated that the adsorbents could be recycled in the removal of Cr(VI).
      It indicated that the hybridization with carbon spheres could enhance the
      adsorption performance of alpha-Fe2O3, which might be used as convenient
      adsorbent to remove heavy metal in industry.

PMID- 29448530
TI  - Effect of Surface Functionalization on Structural and Optical Properties of
      Luminescent LaF3:Sm Nanoparticles.
AB  - Samarium (Sm3+)-doped LaF3 nanoparticles (NPs) subsequently encapsulated with
      inert crystalline LaF3 and amorphous silica layers were prepared by polyol and
      sol-gel chemical process, respectively. These surface modified core/shell/SiO2
      nanostructured were characterized by X-ray diffraction (XRD), FE-transmission
      electron microscopy (TEM), thermal analysis, FTIR, UV/Vis absorption, bang gap
      energy and photoluminescence spectroscopy. The FETEM, EDX and FTIR spectral
      studies clearly revealed that the silica layer has been formed surrounding the
      core-NPs. Comparative spectral analysis indicated that core/shell/SiO2-NPs
      revealed high solubility in aqueous and non-aqueous solvents. The decrease in
      band gap energy after surface growth of an inert LaF3 and silica shells is
      directly correlated to the increase in grain size. On comparing the emission
      intensity, a significant enhancement was observed after inert layer coating,
      whereas, it suppress after silica encapsulation due to the non-radiative
      transitions. The increase luminescent intensity after inert shell growth
      indicates that a significant amount of non-radiative centers existing on the
      surface of core/shell nanoparticles can be eliminated by the shielding effect of
      LaF3 shells. These observed results indicate that the as-prepared core/shell/SiO2
      NPs could be highly useful in broad photonic based applications such as optical
      sensor/optical bio-probe and light emitting diode.

PMID- 29448531
TI  - Thermal Stability and Flame Retardancy of Polypropylene/NiAl Layered Double
      Hydroxide Nanocomposites.
AB  - NiAl layered double hydroxide (NiAl-LDH) was synthesized by co-precipitation
      method. And sodium dodecyl sulphate (SDS) as modifier was utilized to enlarge the
      d-spacing of NiAl-LDH to obtain SDS-NiAl-LDH. PP/SDS-NiAl-LDH nanocomposites were
      prepared with different amount of SDS- NiAl-LDH and PP by melt intercalation
      method. The results of XRD and TEM confirmed that intercalated and exfoliated
      intercalated structures were formed. Compared with pure PP, PP/SDS- NiAl-LDH
      nanocomposites exhibited high thermal stability and residual to the presence of
      barrier effect of NiAl-LDH layers. Cone calorimetry analysis indicated that
      incorporation of SDS-NiAl-LDH obviously improved flame retardancy and smoke
      suppression properties of PP. With the addition of 5 wt% SDS-NiAl-LDH, the peak
      heat release rate (PHRR), the total heat release (THR) and smoke production rate
      (SPR) peak values reduced 32.4%, 16.0%, and 61.5% compared with those of pure PP,
      which were attributed to the barrier effect and excellent charing performance of
      SDS-NiAl-LDH.

PMID- 29448532
TI  - Fabrication of a Hierarchical TiO2 Microsphere/Carbon Dots Photocatalyst for
      Oxygen Evolution and Dye Degradation Under Visible Light.
AB  - Anatase hierarchical TiO2 microsphere/carbon dots composite (HTM/CDs) was
      fabricated by a facile method for active visible light photocatalysis. The phase,
      morphology, microstructure and optical properties were investigated by X-ray
      diffraction, scanning electronmicroscopy, transmission electron microscopy and UV
      VIS diffuse reflectance spectroscopy respectively. Under visible light
      illumination, the fabricated HTM/CDs composite was exhibited an enhanced photo
      catalytic activity compared to that of pure hierarchical TiO2 microspheres (HTM).
      Such an enhancement in photocatalytic activity can be attributed to an increase
      in the absorption of visible light. The photocatalytic activity was investigated
      by the degradation of a model dyemalachite green (MG) and oxygen production
      through water splitting.We believe that this type of hybrid material could be
      used as a highly active and stable visible light photocatalyst to remove
      pollutants as well as energy production with high performance.

PMID- 29448533
TI  - A Novel Method of Electrical Measurement for Stacking Error in 3D/2.5D
      Integration.
AB  - A novel method for the inspection of the stacking misalignment in three
      dimensional integration circuit (3DIC) by using electrical measurement is
      proposed. The metal line pattern designed in this paper combined with bump-less
      TSV fabrication process can successfully detect the direction and quantity of
      stacking fault. In addition, circuit combined with testing structure can be
      developed and simulated by using the current mirror concept and offered
      measurements with better efficiency.

PMID- 29448534
TI  - Kinetics of Glycerol Steam Reforming for Hydrogen Production Over Ni-Fe-Ce/Al2O3
      Catalysts.
AB  - In this work, we investigated glycerol reaction order and activation energy to
      obtain several kinetic parameters in glycerol steam reforming reaction. Glycerol
      steam reforming for kinetics studies was carried out between 450  degrees C and
      550  degrees C under atmospheric pressure with the glycerol concentration of 12
      30 wt% in fixed-bed reactor. Kinetic parameters were obtained in the kinetically
      controlled reaction area. We also used the initial rate method to avoid effect on
      carbon deposition on surface of a catalyst. The glycerol reaction order and
      activation energy were calculated by power-law method and Arrhenius equation,
      respectively.

PMID- 29448535
TI  - Preparation of Poly(Methyl Methacrylate)/Silica Hybrid Film with Dispersed ZnO
      Quantum Dots.
AB  - Quantum dots have recently been adopted in display devices for color compensation
      with light emitting diodes (LEDs). One of the major limitations in using QDs is
      the thermal instability of photoluminescence (PL) owing to the heat dissipation
      of LEDs. In this study, transparent hybrid films of ZnO quantum dots (QDs)
      dispersed in poly(methyl methacrylate) (PMMA) with silica were prepared, and the
      thermal stability of the fluorescence of the films was investigated. ZnO QDs were
      synthesized by a thermal decomposition process and exhibited a PL emission peak
      at 475 nm with excitation at 320 nm. The ZnO QDs were spherical in shape with an
      average diameter of 3 nm. The PL intensity of the ZnO QD-PMMA films decreased
      with an increase in temperature. With increased silica content in the ZnO QD
      PMMA/silica films, the PL quenching was reduced.

PMID- 29448536
TI  - Catalytic Pyrolysis of Municipal Plastic Film Wastes Over Nanoporous Al-MCM-41.
AB  - A mesoporous material, Al-MCM-41, was applied to the catalytic pyrolysis of
      municipal plastic film waste (MPFW) to produce large amounts of valuable
      hydrocarbons. Compared to non-catalytic pyrolysis, the catalytic pyrolysis of
      MPFW over Al-MCM-41 revealed a lower decomposition temperature and activation
      energy upon thermogravimetric analysis. Heavy aliphatic hydrocarbons, which are
      the major products of non-catalytic pyrolysis, were cracked into small
      hydrocarbons and converted efficiently to aromatic hydrocarbons by catalytic
      pyrolysis over Al-MCM-41. The activity of catalytic conversion was enhanced by
      increasing the catalyst to reactant ratio.

PMID- 29448537
TI  - Immunoreaction-Mediated Aggregation of Gold Nanoparticles for Sensitive and
      Selective Assay of Hepatitis B Surface Antigen.
AB  - A rapid, sensitive and quantitative assay method for Hepatitis B surface antigen
      (HBsAg) is of paramount importance for the drug development and in the diagnosis
      of this disease. Here, we proposed a novel biosensor that sensitively and
      selectively screen Hepatitis B surface antigen. This strategy relies on the cross
      linking aggregation of gold nanoparticles (AuNPs) that were decorated with
      Hepatitis B surface antibody (HBsAb) and Raman reporter 5-thio-nitrobenzoic acid
      (TNB) by Hepatitis B surface antigen. The immune reaction between HBsAb and HBsAg
      offers this strategy high specificity, and the use of AuNPs additionally allows a
      visual and homogeneous assay format, thus permitting improved simplicity and
      throughput of the assays. The selectivity and sensitivity in HBsAg assay were
      achieved with a wide linear response range from 0.5 ng/mL to 50 ng/mL and a
      detection limit of 0.2 ng/mL. The results indicated that this strategy can offer
      a simple, robust and convenient platform for HBsAg analysis and related
      biochemical studies with high sensitivity and selectivity.

PMID- 29448538
TI  - One-Step RF-CVD Method for the Synthesis of Graphene Decorated with Metal and
      Metal Oxide Nanoparticles.
AB  - Bilayer and few layer-graphene (Gr) with noble metal (Ag and Au) and TiO2
      nanoparticles were synthesized using atmospheric pressure radio frequency
      chemical vapor deposition (APRF-CVD). The precursors for the formation of the
      respective nanoparticles were dissolved in ethanol and injected into the APRF-CVD
      containing a Cu foil catalyst at 1000  degrees C. The graphene obtained had a
      blistered morphology similar to bubble-wrap. The bubble-like protrusions on the
      graphene sheet were caused by large nanoparticle clusters (~220 nm) formed below
      the graphene sheets. Smaller nanoparticles (10-80 nm) were also observed on top
      of the graphene sheets. Encapsulation of the nanoparticles with graphene, to
      yield core-shell particles was observed. Similarly, secondary growth of carbon
      nanotubes (CNTs) from the Au nanoparticles was observed. The average full width
      half maxima (FWHM) of 2D bands in the Raman spectra indicate that the graphene
      formed was predominantly bilayer graphene for Gr-TiO2 (55 +/- 1.72 cm-1), and few
      layer graphene for Gr-Ag (76 +/- 22 cm-1) and Gr-Au (88 +/- 4.7 cm-1). Raman
      spectroscopy also showed evidence for the doping of graphene and surface-enhanced
      Raman sensitivity (SERS) in the materials. These electronic properties of
      graphene with nanoparticles are relevant to various applications such as
      optoelectronics, catalysis, chemical and biological sensing.

PMID- 29448539
TI  - Ag@Fe3O4 Core-Shell Surface-Enhanced Raman Scattering Probe for Trace Arsenate
      Detection.
AB  - Developing an effective and reliable method for trace arsenic (As) detection is a
      prerequisite for improving the safety of drinking water. In this paper, we
      designed and prepared Ag@Fe3O4 core-shell nanoparticles (NPs), which were then
      used as Surface-Enhanced Raman Scattering (SERS) probe for trace arsenate (As(V))
      detection. The Ag@Fe3O4 core-shell NPs were prepared by in situ growth of Fe3O4
      NPs on the surface of AgNPs, which can effectively combine the strong adsorption
      ability of Fe3O4 nanoshells to As(V) with high SERS activity of Ag nanocores to
      decrease the detection limit. By use of Ag@Fe3O4 core-shell NPs for As(V)
      detection, the detection limit can be as low as 10 MUg/L, and a good linear
      relationship between the SERS intensity of As(V) and their concentrations in the
      range from 10 to 500 MUg/L was achieved. Furthermore, Ag@Fe3O4 core-shell NPs
      could be regenerated through desorption of As(V) from Fe3O4 nanoshells in NaOH
      solution, and then used for recyclic SERS detection. Therefore, it has been
      demonstrated for the first time that multifunctional Ag@Fe3O4 core-shell SERS
      probe could be applied to realize the highly sensitive and reversible detection
      of As(V).

PMID- 29448540
TI  - Investigation of Electrochemical Studies of Magnesium Ion Conducting Poly(vinyl
      alcohol)-Poly(vinyl pyrrolidone) Based Blend Polymers.
AB  - Polymer blend electrolytes based on magnesium ion conducting PVA-PVP-MgCl2
      polymer were prepared at different compositions by solution casting techniques.
      The prepared films were characterised by various techniques such as XRD and FTIR.
      Amorphous nature and structural coordination of polymer electrolyte were
      confirmed by X-ray diffraction and Fourier transform infrared spectroscopy
      studies. The ionic conductivity of the prepared polymer electrolytes were
      analysed through ac impedance spectroscopy. The highest conductivity was found to
      be in the order of ~10-6 Scm-1 at an ambient temperature for the composition of
      50PVA:50PVP:5 wt% MgCl2. Conductivity versus temperature plot was found to follow
      an Arrhenius nature. The dielectric behaviour and ionic transport properties of
      the polymer electrolytes were also analyzed.

PMID- 29448541
TI  - Preparation of Polyurethane Acrylate Coated Carbon Nanotube Nanocomposites by
      Emulsion Polymerization.
AB  - The aim of this work was to prepare strong and conductive polyurethane acrylate
      nanocomposites. First, urethane prepolymers with different molecular weights and
      hydrophilicities were synthetized. Then, their corresponding polyurethane
      acrylate nanocomposites were prepared by ultrasonically-assisted emulsion
      polymerization in the presence of various ratios of urethane prepolymers and
      acrylate monomers. Thermogravimetric analysis (TGA) and tensile results showed
      that thermal stability and mechanical properties of polyurethane acrylate samples
      are significantly dependent on the molecular weight and hydrophilicity of the
      urethane prepolymer as well as the content of acrylate monomers. Polyurethane
      acrylate sample (i.e., PUAc-2B50) with optimum mechanical properties and thermal
      stability were chosen as matrix to prepare nanocomposites in the presence of
      nanotubes grafted with polymerizable acrylate groups (G-MWNTs). Transmission
      electron microscope (TEM) revealed that the surface of nanotubes is uniformly
      coated with polymer nanoparticles. The nanocomposites containing 3 wt% G-MWNTs
      demonstrated a great modulus up to 374 MPa and excellent strength up to 18.74
      MPa. Meanwhile, they indicated remarkable high electrical and thermal
      conductivities; as the electrical conductivity of the nanocomposites increased by
      more than twelve orders of magnitude, and thermal conductivity reached to 12.5
      times of the neat matrix. The developed nanocomposites hold high potential for
      diverse applications, such as printable electronic devices, nano-sensors, and
      heat/electrical induced shape memory polymers.

PMID- 29448542
TI  - Solvothermal Synthesis of Sphere-Like ZnS Microparticles and Its Visible-Light
      Catalytic Properties.
AB  - The cauliflower-like ZnS microspheres consisting of the nanospheres were prepared
      via one step template-free approach employing a solvothermal process using
      Zn(NO3)2.6H2O and CH4N2S as precursors in the mixture solution. The morphology,
      structure characterization, and crystal structure of the as-prepared ZnS were
      performed by X-ray diffraction, scanning electron microscopy, UV-visible
      absorption, and X-ray photoelectron spectroscopy. The results showed that
      cauliflowerlike ZnS microspheres were prepared under this condition and the size
      of the particles were about 3~5 MUm. In addition, the excellent photocatalytic
      activity and degradation mechanism of ZnS microspheres have been investigated and
      discussed in detail. The degradation of Rhodamine B (RhB) aqueous solution was
      carried out to investigate the visible-light catalytic activity under metal
      halide lamp. The results indicated that different size of ZnS had photocatalytic
      activity to RhB under visible light, and sphere-like ZnS displayed high
      photodegradation efficiency with degradation rate of 98% within 140 min.

PMID- 29448543
TI  - Preliminary Study for Measurement of Shear Stress and Hemocompatibility Using
      Commercialized Lab on a Chip.
AB  - We have investigated the effect of flow rate on shear stress and in turn thrombus
      formation on a lab-on-a-chip with a microchannel that is suitable for cell
      culture and growth. Using a combination of Arduino UNO, Arduino Motor Shield, and
      a SERVO stepper motor, we created a pump system that closely mimics the in vivo
      conditions of the human body. With this system, we achieved continuous flow of
      blood and observed attached platelets at the bottom of the collagen coated
      microslide, confirming that with shear stress, thrombus formation increases.

PMID- 29448544
TI  - Mixed Contaminants Removal Efficiency Using Bio-FeS Nanoparticles.
AB  - Advances in nanotechnology has provided diverse industrial applications including
      an environmental remediation field. In particular, bio-nanotechnology gives
      extended eco-friendly remediation practice. Among diverse bio-nanoparticles
      synthesized by microorganisms, the iron based nanoparticles (NPs) are of great
      interest because of their availability, low cost and toxicity to human health and
      the environment. In this study, iron based nanoparticles were biologically
      synthesized and mineralogically identified. Also, the removal efficiency of mixed
      contaminants, high As(III)-low Cr(VI) and high As(V)-low Cr(VI), using these bio
      nanoparticles were conducted. As a result, biologically synthesized NPs were
      identified as FeS complex and their catalytic capacity showed highly effective to
      immobilize more than 97% of mixed contaminants by adsorption/mineralization.

PMID- 29448545
TI  - Enhanced Photosensing and Photodynamic Treatment of Colon Cancer Cells Using
      Methoxy Poly(ethylene glycol)-Conjugated Chlorin e6.
AB  - Nanophotosensitizer composed of methoxy poly(ethylene glycol) (MePEG) and chlorin
      e6 (Ce6) (abbreviated as Pe6) was synthesized for efficient delivery of Ce6 to
      the colon cancer cells. Pe6 nanophotosensitizer has small diameter less than 100
      nm with spherical shape and core-shell structure. They were activated in aqueous
      solution while Ce6 was quenched due to its poor aqueous solubility. They showed
      no intrinsic cytotoxicity against normal cells and colon cancer cells. Pe6
      nanophotosensitizers showed enhanced cellular uptake, phototoxicity, and reactive
      oxygen species (ROS) generation at in vitro cell culture experiment. Furthermore,
      they showed improved tumor tissue penetration and accumulation in vivo animal
      studies. We suggested Pe6 nanophotosensitizers as an ideal candidate for PDT of
      colon cancer.

PMID- 29448546
TI  - Microbially Induced Formation of Fe Carbonates by Metal-Reducing Bacteria
      Enriched from a CO2 Repository Candidate Site.
AB  - The objectives of this research were to study the microbial diversity of metal
      reducing bacteria enriched from sedimentary rock collected from a CO2 repository
      candidate site and to examine the effect that the bicarbonate concentration had
      on the iron reduction and biomineralization by the cultures. The enriched metal
      reducing bacteria (i.e., JG-3) consisted mostly of Exiguobacterium sp. and
      Shewanella sp., and the microbial reduction of akaganeite (beta-FeOOH), an
      Fe(III) oxyhydroxide, was examined over 7 days of bacterial cultivation at 30 
      degrees C under different concentrations of bicarbonate (0~210 mM). The
      akaganeite (beta-FeOOH) transformed into goethite (alpha-FeOOH) and magnetite
      (Fe3O4) in low HCO-3 buffered medium (<70 mM) and was transformed to magnetite
      and siderite (FeCO3) in high HCO-3 buffered medium (>140 mM). These results
      indicate that metal- reducing bacteria from a deep subsurface environment reduce
      and transform an iron oxyhydroxide to siderite (FeCO3) in HCO-3 buffered medium
      and that microbial iron reduction may accelerate the mineral trapping of CO2 for
      deep geologic sequestration.

PMID- 29448547
TI  - Synthesis of Cu-In-S/ZnS Quantum Dots in Aqueous Phase by Microwave Irradiation.
AB  - Recently various nanomaterials have been prepared using the microwave irradiation
      technology because of its advantages over conventional thermal decomposition
      methods such as the precise control of reaction temperature, lower energy
      consumption, and target-oriented uniform heating. In this study, water-soluble Cu
      In-S/ZnS core/shell quantum dots (QDs) with average size in the range 3.5-3.7 nm
      were successfully synthesized in aqueous phase by microwave irradiation. L
      glutathione and trisodium citrate dihydrate were used as a stabilizer between
      indium and copper ions. A strong photoluminescence (PL) emission peak was
      observed from the QDs prepared in weak acidic conditions. With longer reaction
      times and higher In/Cu ratios, we observed redshift in the PL spectra.

PMID- 29448548
TI  - Nano-Sized Fume Biogas Production from Food Waster Using Semi-Continuous
      Anaerobic Digester.
AB  - In this study, the nano-sized fume biogas production from food waste was
      investigated using lab scale semi-continuous stirred tank reactor (SCSTR) at 35 
      degrees C with 30d HRT and 30L working volume. The mesophilic digestion test was
      performed with three different feed materials (food waste) and food to
      microorganism (F/M) ratios (0.13, 0.34, and 0.27) in the same experiment. The
      results showed that the F/M ratios significantly affected the biogas production
      rate. The highest production rate was obtained at F/M ratio of 0.13. Nano-sized
      fume biogas produced in anaerobic digestion consists of 68.7% CH4, 31.2% CO2 and
      30~200 nm particle. The average nano-sized fume biogas and methane production of
      digester were 29.96 L/Kg versus day-1 and 20.58 L/Kg versus day-1, respectively.
      The CH4 could be calculated as the heat energy 1.85 Kcal/Kg VS day-1. The
      digestion was operated without addition of chemicals or nutrients into the
      system.

PMID- 29448549
TI  - Fabrication and Magnetic Properties of Co2MnAl Heusler Alloys by Mechanical
      Alloying.
AB  - We have applied mechanical alloying (MA) to produce nanocrystalline Co2MnAl
      Heusler alloys using a mixture of elemental Co50Mn25Al25 powders. An optimal
      milling and heat treatment conditions to obtain a Co2MnAl Heusler phase with fine
      microstructure were investigated by X-ray diffraction, differential scanning
      calorimeter and vibrating sample magnetometer measurements. alpha-(Co, Mn, Al)
      FCC phases coupled with amorphous phase are obtained after 3 hours of MA without
      any evidence for the formation of Co2MnAl alloys. On the other hand, a Co2MnAl
      Heusler alloys can be obtained by the heat treatment of all MA samples up to 650 
      degrees C. X-ray diffraction result shows that the average grain size of Co2MnAl
      Heusler alloys prepared by MA for 5 h and heat treatment is in the range of 95
      nm. The saturation magnetization of MA powders decreases with MA time due to the
      magnetic dilution by alloying with nonmagnetic Mn and Al elements. The magnetic
      hardening due to the reduction of the grain size with ball milling is also
      observed. However, the saturation magnetization of MA powders after heat
      treatment increases with MA time and reaches to a maximum value of 105 emu/g
      after 5 h of MA. It can be also seen that the coercivity of 5 h MA sample
      annealed at 650  degrees C is fairly low value of 25 Oe.

PMID- 29448550
TI  - Effect of the Manganese Phosphate Solution with Additive Agent of Tartaric Acid.
AB  - In this study, the correlation between morphology and friction of manganese
      phosphate coating layer with additive agent of tartaric acid by 2, 4, 6 g were
      investigated. The microstructure and morphology of the coatings were studied by
      scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive X
      ray spectroscopy (EDS) and atomic force microscopic (AFM). Potentiodynamic
      polarization test was carried out in order to evaluate the corrosion protection
      properties of manganese phosphate coating in 3.5 wt.% NaCl solution. Also, the
      tribology property of manganese phophate coating was tested by ball-on disk. In
      the results of EDS analysis, coating layer consists of elements such as Mn, P,
      Fe, O, and C. XRD showed that (Mn, Fe)5H2(PO4)4.4H2O in manganese phosphate
      coating layer was formed by the chemical reaction between manganese phosphate and
      elements in SM45C alloy. The corrosion resistance of manganese phosphate coating
      with additive agent was superior than the one without additive agent. Also, in
      the Fe amount in sludge, manganese phosphate coating layer with additive agent
      was observed to be considerably decreased.

PMID- 29448551
TI  - Synthesis and Characterization of Cation-Exchange Fibers with Radiation-Induced
      Grafting of Glycidyl Methacrylate onto Cotton Cellulose.
AB  - Conventional ion exchange beads are used for purification and demineralization of
      water and for various other applications in the chemical synthesis,
      hydrometallurgy, and agricultural industries. However, there are some
      disadvantages associated with ion exchange beads, such as distillation causing
      porosity during solvent removal, pre-swelling of beads to allow for core
      functionalization, and pre-swelling of beads overnight prior to end use. Fibrous
      ion exchange materials have advantages over the conventional ion exchange beads,
      including simplification of the overall preparation. In this study, a cation
      exchange fiber was prepared by a radiation-induced grafting method. Glycidyl
      methacrylate (GMA) was grafted onto cotton cellulose using a pre-irradiation
      method by electronbeam irradiation. Sequential treatment with sulfonic acid was
      performed to react with the cation pollutants. The degree of grafting increased
      up to 812% with the increase of absorbed dose, reaction time and monomer
      concentration. It was found that the sulfonation reaction occurred smoothly with
      10% sodium sulfite solution, and a high 2.0 meq/g ion exchange capacity was
      obtained from 140% GMA-grafted non-woven cotton fabric.

PMID- 29448552
TI  - Plasmonic Screening Effect of Gold Nanoparticles Array on Light Absorption in
      Poly(3-hexyl)Thiophene Thin Film.
AB  - The localized surface plasmon (LSP) photophysical phenomenon occurring in metal
      nanostructures is often presented as a way to effectively couple light into sub
      wavelength-scale photovoltaic devices, which would otherwise suffer from a weak
      light absorption. The simultaneous complementary effect of localized optical
      field depletion receives far less attention. We studied a system consisting of a
      planar gold nanoparticles array (AuNP) deposited at the surface of a
      semiconducting polymer thin film (P3HT). By comparing the UV-vis spectra of P3HT
      with and without the AuNP array, we have estimated that the AuNPs screen the
      optical absorption in the interfacial layer of about 3.8 nm effective thickness
      due the near-field depletion effect. It suggests that the AuNP array may be used
      to practically "hide" a thin semiconductor layer, e.g., in order to tune the
      perceived color of the photovoltaic cell embedded in architecture, or in wearable
      devices.

PMID- 29448553
TI  - Bio-Based PA11/Graphene Nanocomposites Prepared by In Situ Polymerization.
AB  - Bio-based polyamide 11 (PA11)-graphene nanocomposites with different filler
      concentrations (0.25, 0.5, 0.75, 1.5 and 3 wt%) were prepared by In Situ
      polymerization starting from a water dispersed suspension of graphene
      nanoplatelets. The effects of the incorporation of the filler were studied in
      terms of molecular, morphological, thermal and dynamic mechanical properties of
      the final materials. During the crystallization process from the melt, the filler
      induces a notable nucleating effect even if the crystal growth rate tends to
      decrease. The glass transition temperature tends to shift to higher temperatures
      indicating a decrement of the molecular mobility. Thermal stability is enhanced
      confirming a good filler dispersion into the matrix. Mechanical reinforcement,
      investigated by means of a dynamic mechanical thermal analyzer was also
      highlighted. It was observed that a graphene concentration of 0.75 wt% induces
      the highest final performances.

PMID- 29448554
TI  - Conductive Adhesive Based on Mussel-Inspired Graphene Decoration with Silver
      Nanoparticles.
AB  - Decoration with silver nanoparticles was obtained by coating graphene with a
      polydopamine layer, able to induce spontaneous metallic nanoparticles formation
      without any specific chemical interfacial modifier, neither using complex
      instrumentation. The choice of dopamine was inspired by the composition of
      adhesive proteins in mussels, related to their robust attach to solid surfaces.
      The synthesis procedure started from graphite and involved eco-friendly
      compounds, such as Vitamin C and glucose as reducing agent and water as reaction
      medium. Silver decorated graphene was inserted as secondary nanofiller in the
      formulation of a reference conductive adhesive based on epoxy resin and silver
      flakes. A wide characterization of the intermediate materials obtained along the
      step procedure for the adhesive preparation was carried out by several
      techniques. We have found that the presence of nanofiller yields, in addition to
      an improvement of the thermal conductivity (up to 7.6 W/m . K), a dramatic
      enhancement of the electrical conductivity of the adhesive. In particular,
      starting from 3 . 102 S/cm of the reference adhesive, we obtained a value of 4 .
      104 S/cm at a nanofiller concentration of 11.5 wt%. The combined double filler
      conductivity was evaluated by Zallen's model. The effect of the temperature on
      the resistivity of the adhesive has been also studied.

PMID- 29448555
TI  - The Role of Cu2O Mesoporous Spheres in the Removal of Organic Pollutants:
      Photocatalyst or Adsorbent?
AB  - Cuprous oxide (Cu2O) is a kind of functional and promising energy material, which
      has been used as solar cells, adsorbents, and lithium ion battery electrode
      materials. And its mainly application is toward photocatalytic reactivity of
      organics' decomposition under visible light irradiation. However, the real role
      of Cu2O remains debated, for these reports don't give a powerful evidence to
      prove its significant photocatalytic properties. Here, we describe a one-pot
      synthesis method to construct Cu2O mesoporous spheres with large specific surface
      area at room temperature. This mesoporous microstructure is controlled through an
      Ostwald ripening-based dissolved partly process. And Cu2O mesoporous spheres are
      used to study the property of removing organic pollutants. We distinguish the
      real role of Cu2O by carefully measure the reduced portion of photocatalyst or
      adsorbent, while it is reacting with organic pollutants. At last, we find out the
      reason that has caused the concentration of organic pollutants to decrease is
      mainly based on the adsorption property of Cu2O, rather than its photocatalytic
      effect. However, the photocatalytic effect of Cu2O is very low under visible
      light irradiation.

PMID- 29448556
TI  - Facile and Efficient Synthesis of Tetrahydrobenzimidazo [2,1-b]Quinazolin-1(2H)
      One Derivatives Using Bronsted Acidic Ionic Liquid Immobilized on Nanoporous Na+
      Montmorillonite.
AB  - In this work, an efficient and green procedure have been described for the
      synthesis of tetrahydrobenzimidazo[2,1-b]quinazolin-1(2H)-one derivatives using
      nanoporous sodium montmorillonite clay (Na+-MMT) modified with 1-methyl-3
      (trimethoxysilylpropyl)-imidazolium hydrogen sulfate (Na+-MMT-[pmim]HSO4). The
      procedure gave the products in excellent yields in very short reaction times
      under solvent-free condition. Also this catalyst can be reused for six times
      without considerable loss of its catalytic activity.

PMID- 29448557
TI  - Optimization of Resistance Load in 4T-Static Random-Access Memory Cell Based on
      Silicon Nanowire Transistor.
AB  - This study explores optimization of resistance load (R-Load) of four silicon
      nanowire transistor (SiNWT)-based static random-access memory (SRAM) cell. Noise
      margins and inflection voltage of butterfly characteristics with static power
      consumption of SRAM cell are used as limiting factors in this optimization. Range
      of R-Load used in this study was 20-1000 KOmega with Vdd = 1 V. Results indicate
      that optimization depends critically on resistance load value. The optimized
      range of R-Load is 100-200 KOmega.

PMID- 29448558
TI  - Three-Dimensional ZnO Nanostructure Based Gas and Humidity Sensors.
AB  - The ZnO nanostructure environmental sensors were prepared via the three
      dimensional through silicon via (3D-TSV) technique. For 3D-TSV, the diameter and
      length of the Si via were about 200 and 400 MUm, respectively. For nitrogen oxide
      (NO), the measured responses were around ~12, ~16, and ~20% when the
      concentrations of the injected NO gas were 20, 40 and 60 ppm, respectively. For
      humidity and temperature sensing, the measured nanowire current increased
      logarithmically with increasing chamber temperature. The response to relative
      humidity increased with increasing temperature.

PMID- 29448559
TI  - Thermally Deposited Palladium-Tungsten Carbide and Platinum-Tungsten Carbide
      Counter Electrodes for a High Performance Dye-Sensitized Solar Cell Based on
      Organic T-/T2 Electrolyte.
AB  - Tungsten carbide (WC) particles (~1 MUm) were dispersed in DI water and dropped
      onto conductive glass. The resulting WC films were used as dye-sensitized solar
      cell (DSSC) counter electrodes. The performance of the WC DSSC based on the
      organic thiolate/disulfide (T-/T2) electrolyte was ~0.78%. The cell efficiency
      was greatly improved after decorating palladium (Pd) or platinum (Pt)
      nanoparticles on WC particles with a promising efficiency of ~2.15% for Pd-WC
      DSSC and ~4.62% for Pt-WC DSSC. The efficiency improvement of the composited (Pd
      WC and Pt-WC) cells is attributed to co-functioning catalysts, the large
      electrode interfacial area and a low charge-transfer resistance at the
      electrolyte/counter electrode interface.

PMID- 29448560
TI  - Crystal Structure and Antioxidant Activity of 5,6-O-(4-chlorophenyl)-L-Ascorbic
      Acid Synthesized with Nanosolid Superacid.
AB  - The title compound 5,6-O-(4-chlorophenyl)-L-ascorbic acid (C13H11ClO6) was
      synthesized using nanosolid superacid SO2-4/SnO2 as a catalyst and its structure
      was characterized by IR, 1H NMR and single-crystal X-ray diffraction. 1H NMR data
      indicated the product is a mixture of two diastereomer compounds (a(7S) and
      b(7R)). And the crystal of one diastereomer compound a(7S) belongs to
      orthorhombic system, space group P212121 with a = 6.501(4), b = 7.803(5), c =
      25.013(15) A, V 1268.7(13) A3, Z = 4, Dc 1.564g/cm3, MU(Mo-Kalpha) = 0.325 mm-1,
      F(000) = 616, R = 0.0255 and wR(I > 2sigma (I)) = 0.0624. X-ray crystal structure
      data display that the hydrogen bonding interactions observed link the molecules
      to form a three-dimensional system. In addition, 5,6-O-(4-chlorophenyl)-L
      ascorbic acid (CPAA) exhibited strong free-radical scavenging activities in vitro
      against 2,2-diphenyl-1-picrylhydrazyl and superoxide anion. Therefore, CPAA
      should be investigated further as a worthy antioxidant.

PMID- 29448561
TI  - Electrical and Optical Properties of In2O3 Thin Films Deposited on Sapphire
      Substrate.
AB  - In2O3 thin films were prepared on c-plane sapphire substrates using laser
      molecular beam epitaxy technique. The X-ray diffraction (XRD) patterns revealed
      that the In2O3 thin films were highly oriented along the (111) direction. The
      intensity of (222) diffraction peaks mainly depend on growth temperature, and the
      crystallite sizes mainly depend on oxygen pressure. The carrier concentrations
      exhibit a decrease with increasing growth temperature and oxygen pressure,
      meantime, the resistivity increase. The red shift of In2O3 thin films respect to
      that of bulk In2O3 can be explained by defect energy levels formation, the blue
      shift of In2O3 thin films depends on carrier concentration, can be explained by
      Burstein-Moss band-filling effect.

PMID- 29448562
TI  - Microwave Absorption Properties of Uniform Ultra-Long SiC Nanowires.
AB  - The uniform ultra-long SiC nanowires (SiCNWs) were incorporated into the epoxy
      matrix to characterize the morphology effect on their electromagnetic wave
      absorption performance. The ultra-long SiCNWs with lengths of hundreds of
      micrometers were fabricated by chemical vapor deposition technique at 1250 
      degrees C, and have diameters of 10-60 nm with uniform morphologies. The
      microwave absorption performance of SiCNW/epoxy resin composites was investigated
      in the range of 8-18 GHz. Significant absorbing properties were discovered in the
      composites at frequencies of 8-12.4 GHz, comparing with a control sample. The
      slightest reflection loss (RL) value of -0.5 dB was obtained at 15 GHz at a very
      small SiCNWs concentration of 0.05 wt%. The significant absorbing properties of
      the uniform ultra-long SiCNWs at low frequencies can be mainly attributed to
      homogeneous small diameters to reduce the electromagnetic wave reflectance, high
      density interfacial polarization, complex conductive network structure and
      quantum effect.

PMID- 29448563
TI  - Sensing Properties of ZnO Nanoparticles for Detection of 2-Chloroethyl Ethyl
      Sulfide as a Mustard Simulant.
AB  - In this work, we present the fabrication and characterization of a 2-chloroethyl
      ethyl sulfide (2-CEES) gas sensor based on ZnO nanoparticles (NPs) synthesized by
      a hydrothermal method. We confirmed that synthesized ZnO NPs adopt a
      polycrystalline phase. Partially aggregated ZnO-NPs revealed spherical or
      ellipsoidal nanocrystalline particles in a size range of 30-50 nm, as observed by
      field-emission scanning electron microscopy (FE-SEM). The maximum response of the
      ZnO NPs was 15 at 1 ppm 2-CEES concentration, and a low detection limit of 0.4
      ppm was observed at an optimal operating temperature of 250  degrees C. The
      lowest response time was 6 s in 20 ppm at 250  degrees C. The linearity response
      with correlation coefficient (R2) was 0.9887 at 2-CEE concentrations of 0.4-1 ppm
      at the operating temperature of 250  degrees C. The enhanced sensing performance
      and a decrease in the operating temperature were attributed to a high specific
      surface area and more active sites in the ZnO NPs after exposure to 2-CEES.

PMID- 29448564
TI  - Biocompatibility Evaluation of Feldspathic Porcelain with Nano-Sized Silver Ion
      Particles.
AB  - The major failure of dental restorations is caused by dental caries by S. mutans.
      This study evaluated the effect of nanosized silver ions in feldspathic porcelain
      on cytotoxicity and antimicrobial activity. The control group was feldspathic
      porcelain (Noritake EX-3, Kuraray Noritake Dental Inc., Japan) that did not
      contain Ag (silver). The experimental groups were feldspathic porcelain mixed
      with colloidal solutions of nanosized silver ions in mixtures of 5% 10%, 20%,
      30%. Cell activity assays evaluated with osteoblast hFOB 1.19 cells (human Fetal
      Osteoblastic cell line, ATCC(r) CRL- 11372TM) and antimicrobial activity test
      used the streptococcus mutans (S. mutans). According to the observations, the
      addition of Ag to feldspathic porcelain led to increased cell activity and showed
      excellent antibacterial performance. Especially, the feldspathic porcelain with
      30% nanosized Ag ion appeared to have a significant antimicrobial effect, this
      allows for the possibility of various clinical applications for such material,
      including use in dental prosthesis and implants.

PMID- 29448565
TI  - Synthesis and Thermal Stability of Nanocrystalline Tetragonal Zirconia by
      Hydrolysis with Ethylene Diamine.
AB  - Nanocrystalline zirconia with high surface area and pure tetragonal crystalline
      phase was prepared using ethylene diamine (EDA), which acts as both precipitating
      agent and dispersant of the zirconium precursor. The yttria stabilized zirconia
      (Y-TZP) is a very attractive material due to its excellent biocompatibility, high
      fracture toughness, high strength and low wear rates. So zirconyl chloride
      octahydrate (ZrOCl2 . 8H2O) and yttrium chloride hexahydrate (YCl3 . 6H2O) in
      different molar ratios were used as starting solution. The detailed effects of
      various process parameters such as reaction time, concentration of the precursor
      solution, amount of ethylene diamine, and calcination temperature on the
      structural properties of the zirconia powders were investigated. The preparation
      conditions significantly affected the structural stability, crystal size, and
      crystal phase of the final material. Increases in the reaction time and amount of
      ethylene diamine led to a substantial increase of the crystal growth rate, the
      specific surface area, and the tetragonal content of the zirconia.

PMID- 29448566
TI  - Highly Efficient Electrochemical Detection of Phenolic Compounds Utilizing
      Superior Catalytic Activity of Nanohybrids Consisting of Magnetic Nanoparticles
      and Gold Nanoclusters.
AB  - Although Fe3O4 magnetic nanoparticles (MNPs) have gathered particular interest as
      potent peroxidase mimetics, their practical utility has been critically limited
      by their low catalytic activity. Here, we have developed a nanohybrid material to
      significantly enhance the catalytic activity of MNPs by incorporating other
      enzyme mimetics, gold nanoclusters (AuNCs), through electrostatic attraction.
      Owing to the synergistic effect of MNPs and AuNCs, the constructed nanohybrid
      yielded highly enhanced peroxidase-like activity and higher resolution in
      electrochemical detection of H2O2 than bare MNPs. The nanohybrids were also
      successfully applied to detecting phenolic compounds including phenol and cresol,
      producing a concentration-dependent increase of cathodic current. Based on this
      result, we expect that the nanohybrids consisting of AuNCs and MNPs can serve as
      potent peroxidase mimetics for environmental monitoring.

PMID- 29448567
TI  - Naphthalene Derivatives End-Capped with 2-(Diphenylamino)-9,9-Diethylfluorenes
      for Blue Organic Light-Emitting Diodes.
AB  - To investigate the electroluminescent (EL) properties of fluorescent materials
      based on fluorene-substituted naphthalene, multilayered OLEDs with the following
      sequence; indium- tin-oxide (ITO)/N,N'-di(1-naphthyl)-N,N'-diphenyl-(1,1'
      biphenyl)-4,4'-diamine (NPB) (50 nm)/Blue emitting materials (30 nm)/4,7-diphenyl
      1,10-phenanthroline (Bphen) (30 nm)/lithium quinolate (Liq) (2 nm)/Al (100 nm)
      were fabricated using these materials as emitters. These devices exhibited blue
      emissions. Particularly, a device using 7-(1-(1-(2-(diphenylamino)-9,9-diethyl-9H
      fluoren-7- yl)naphthalen-4-yl)naphthalen-4-yl)-9,9-diethyl-N,N-diphenyl-9H
      fluoren-2-amine as a blue emitting material exhibited blue emission with a
      luminous efficiency, a power efficiency, an external quantum efficiency, and CIE
      coordinates of 2.79 cd/A, 1.19 lm/W, 2.30% at 1,000 cd/m2, and (0.14, 0.12) at
      8.0 V, respectively. This study demonstrates that 2-(Diphenylamino)-9,9
      diethylfluorenes endcapped naphthalene derivatives have the excellent properties
      for blue emitting materials for OLEDs.

PMID- 29448568
TI  - The Promoting Role of W in Nickel Based Catalyst for Bi-Reforming.
AB  - In the present study, co-impregnated tungsten and silver onto nickel based
      catalysts have been investigated. The influences caused by tungsten modification
      were inspected by XRD, XPS, TPR and TEM with Elemental Mapping from SEM. the
      result revealed similarity in terms of physicochemical properties. By adding
      trace of tungsten subsidiary to silver, it was able to reach as high performance
      as the catalyst with silver only. The modified catalysts showed enhanced
      stability and reactivity by forming large Al2O3 structure.

PMID- 29448569
TI  - Preparation and Performance Validation of Nano-Perovskite Type for Carbon Dioxide
      Reforming of Methane.
AB  - This paper describes the La0.8Sr0.2NiO3 perovskite-type catalysts supported on
      alpha-Al2O3 that were prepared by polyol method and used as a catalyst for the
      carbon dioxide reforming of methane. The effect of the molar concentration of
      polyvinyl-pyrrolidone (PVP) on the reducibility, structural properties and carbon
      deposition was characterized by XRD, and TGA. The carbon dioxide reforming of
      methane on the catalyst was performed at the different concentration of PVP. At
      the 1 M PVP, main characteristic peaks of perovskite structure were established
      without impurities, thus showing the highest catalytic activity; 87.7% and 92.1%
      in CH4 and CO2 conversion, respectively. After the reaction, carbon deposition
      was 0.4-0.6%, while 6.2% on the existing Ni catalyst, indicating the perovskite
      type catalyst has a superior characteristic preventing it from the carbon
      deposition at the carbon dioxide reforming of methane.

PMID- 29448570
TI  - Study on Endurance and Performance of Impregnated Ruthenium Catalyst for Thruster
      System.
AB  - Performance and endurance of the Ru catalyst were studied for nitrous oxide
      monopropellant thruster system. The thermal decomposition of N2O requires a
      considerably high temperature, which make it difficult to be utilized as a
      thruster propellant, while the propellant decomposition temperature can be
      reduced by using the catalyst through the decomposition reaction with the
      propellant. However, the catalyst used for the thruster was frequently exposed to
      high temperature and high-pressure environment. Therefore, the state change of
      the catalyst according to the thruster operation was analyzed. Characterization
      of catalyst used in the operation condition of the thruster was performed using
      FE-SEM and EDS. As a result, performance degradation was occurred due to the
      volatilization of Ru catalyst and reduction of the specific surface area
      according to the phase change of Al2O3.

PMID- 29448571
TI  - Electrocatalytic Stability of Tin Cathode for Electroreduction of CO2 to Formate
      in Aqueous Solution.
AB  - The electrocatalytic stability of tin (Sn) nanoparticle for electrochemical
      reduction of CO2 to formate was measured using an H-type cell during electrolysis
      for 40 h. The Faradaic efficiency (FE) and partial current density (PCD) of
      formate formation reduced as much as 10% and 13% of the maximum values,
      respectively. To elucidate the decrease in FE and PCD, the changes in the
      morphology, chemical composition, the crystalline structure were investigated.
      The spherical Sn nanoparticles were pulverized after electrolysis. Furthermore,
      the crystal structure of the fresh Sn electrocatalyst was collapsed and changed
      into amorphous phase after 40 h electrolysis. The decrease in FE and PCD of
      formate production on the Sn/CFP electrode could be mainly originated from the
      reduction of the SnOx to Sn on the cathode surface during electrolysis.

PMID- 29448572
TI  - DC Magnetron Sputtered IZTO Thin Films for Organic Photovoltaic Application.
AB  - IZTO20 (In0.6Zn0.2Sn0.2O1.5) ceramic target was prepared from oxide mixture of
      In2O3, ZnO, and SnO2 powders. IZTO20 thin films were then deposited onto glass
      substrate at 400  degrees C by DC magnetron sputtering. The average optical
      transmittance determined by ultraviolet-visible spectroscopy was higher than 85%
      for all films. The minimum resistivity of the annealed IZTO20 thin film was
      approximately 6.1*10-4 Omega.cm, which tended to increase with decreasing indium
      content. Substrate heating and annealing were found to be important parameters
      affecting the electrical and optical properties. An organic photovoltaic (OPV)
      cell was fabricated using the IZTO20 film deposited under the optimized condition
      as an anode electrode and the efficiency of up to 80% compared to that of a
      similar OPV cell using ITO film was observed. Reduction of surface roughness and
      electrical resistivity through annealing treatment was found to contribute to the
      improved efficiency of the OPV cell.

PMID- 29448573
TI  - Sol-Gel Deposited Double Layer TiO2 and Al2O3 Anti-Reflection Coating for Silicon
      Solar Cell.
AB  - In this work, the deposition of double layer ARC on p-type Si solar cells was
      carried out by simple spin coating using sol-gel derived Al2O3 and TiO2
      precursors for the fabrication of crystalline Si solar cells. The first ARC layer
      was created by freshly prepared sol-gel derived Al2O3 precursor using spin
      coating technique and then second ARC layer of TiO2 was deposited with sol-gel
      derived TiO2 precursor, which was finally annealed at 400  degrees C. The double
      layer Al2O3/TiO2 ARC on Si wafer exhibited the low average reflectance of 4.74%
      in the wavelength range of 400 and 1000 nm. The fabricated solar cells based on
      double TiO2/Al2O3 ARC attained the conversion efficiency of ~13.95% with short
      circuit current (JSC) of 35.27 mA/cm2, open circuit voltage (VOC) of 593.35 mV
      and fill factor (FF) of 66.67%. Moreover, the fabricated solar cells presented
      relatively low series resistance (Rs) as compared to single layer ARCs, resulting
      in the high VOC and FF.

PMID- 29448574
TI  - Precipitation of Nickel Oxide on TiO2 Photocatalysts for Enhanced Visible
      Degradation Activity.
AB  - The liquid phase plasma (LPP) synthetic process has been exploited to synthesize
      nickel oxide nanoparticles doped TiO2 photocatalyst (NOTP) that can respond to
      visible light. The physicochemical properties of NOTPs were studied by several
      analysis instruments. The nickel oxide nanoparticles precipitated uniformly on
      the TiO2 powder are mostly NiO. The band gap energy of the NOTP measured was 2.99
      eV, which was smaller than that of bare TiO2, 3.12 eV. The NOTP synthesized in
      this work showed high photoactivity under visible blue light.

PMID- 29448575
TI  - Preparation and Characterization of Conductive Polymer Blends of Polypyrrole and
      Poly(ethylene oxide).
AB  - Conductive polymer blends of polypyrrole (PPy) and poly(ethylene oxide) (PEO)
      were obtained in the form of films and fibers, respectively by solvent casting
      and electrospinning. Different amounts of PPy were introduced in the blends in
      order to study the effect of the conductive polymer on the properties of the
      final material and in particular to elucidate the influence of the different
      morphology on conductivity. The structure and morphology of PPy/PEO blends were
      characterized by wide angle X-ray diffraction (WAXD) and small angle X-ray
      scattering (SAXS), differential scanning calorimetry (DSC) and thermogravimetric
      analysis (TGA) were used to understand the influence of different PPy content on
      thermal behavior and stability, electrospun fibrous mats were examined by
      scanning electron microscopy (SEM). The conductivity of the films and fibrous
      mats was measured and correlation with morphology was highlighted.

PMID- 29448576
TI  - Graphene-Pyrene Nanocomposites Obtained Using Azide Chemistry.
AB  - In this study we describe a simple and fast procedure for the covalent
      functionalization of pristine graphene with a pyrene-terminated alkylazide,
      transformed in a highly reactive radical by thermal activation. The
      functionalized graphene sheets showed enhanced dispersibility in organic solvents
      compared to the pristine ones, thus enhancing their solution processability and
      compatibility with solvents or polymers. The relative improvement of solubility
      estimated form the absorption spectra was ~60% in CHCl3 and ~1200% in THF. The
      obtained materials were characterized by optical absorption spectroscopy,
      photoemission spectroscopy, infrared spectroscopy and X-rays photoelectron
      spectroscopy. The presence of the pyrene photoemitting chromophore in the
      grafting unit allowed to monitor the successful grafting and to confirm the
      effectiveness of the alkylazide to improve graphene solubility even when present
      in small amounts on the graphene surface.

PMID- 29448577
TI  - Formation of Metastable Co-Ni Alloy Nanowires in Electrodeposition.
AB  - The effect of potential on the crystal structure and composition of Co-Ni alloy
      nanowires is studied by XRD, FE-SEM and EDX. The deposited alloy nanowires are
      metastable fcc phase Co84.45Ni15.55 at -3.0 V and stable hcp phase Co80.75Ni19.25
      at -1.6 V. The formation of the metastable fcc alloy nanowires can be attributed
      to smaller critical clusters formed at the high potential, as the smaller
      critical clusters favor fcc structure because of the significant surface energy
      effect. The content of Co inside nanowires increases with increasing potential.
      This can be understood by the polarization curves of depositing Co and Ni
      nanowires, which show that the current density ratio of Ni to Co at -1.6 V (0.88)
      is higher than that at -3.0 V (0.73).

PMID- 29448578
TI  - Oxygen and Acrylic Acid Plasma Treatment on Titanium Mesh for Improving the
      Hydroxyapatite Formation.
AB  - Customized titanium (Ti) meshes were treated with O2 plasma and acrylic acid
      plasmapolymerization (PPAAc). The optimum conditions for PPAAc were as follows:
      20 W, 15 mTorr, and 5 min. Hydroxyapatite formation increased in Ti meshes
      treated with O2 and PPAAc compared with that in untreated Ti meshes. Moreover,
      MC3T3-E1 cells exhibited improved cell spreading, attachment, proliferation in
      PPAAc treated Ti mesh than in untreated Ti mesh. This result revealed that O2 and
      PPAAc surface treatment on Ti mesh was potential tool for improving the bone
      formation on the Ti mesh clinically application.

PMID- 29448579
TI  - Resin Bonding to Type IV Gold Alloy Conditioned with a Novel Mercapto Silane
      System: Effect of Incorporation of a Phosphate Monomer.
AB  - Self-assembled monolayers of thiols have been used to link a range of materials
      to planar gold surfaces or gold nanoparticles in nanoscience and nanotechnology.
      Novel mercapto silane systems are a promising alternative to dental noble metal
      alloys for enhanced resin bonding durability Goldbased alloys for full-cast
      restorations contain various base metal elements, which may bond to acidic
      functional monomers chemically, in addition to noble metal elements. This study
      examined how the additional incorporation of a phosphate monomer (di-2
      hydroxyethyl methacryl hydrogenphosphate, DHP) into novel mercapto silane primer
      systems affected the resin bond strength to a type IV gold alloy pretreated with
      the primers. One of three commercial primers (Alloy Primer and M. L. Primer) and
      three experimental primer systems ((1) blend of gamma
      mercaptopropyltrimethoxysilane (SPS) and gamma-methacryloxypropyltrimethoxysilane
      (MPS) (both 1.0 wt%), (2) 1.0 wt% DHP-containing primer, and (3) blend of SPS,
      MPS, and DHP (each 1.0 wt%)) was applied to the alloy surfaces after
      sandblasting. Resin cylinders (diameter: 2.38 mm) were bonded to the surfaces and
      light-cured. All bonded specimens were stored in water at 37  degrees C for 24 h
      and then half of them additionally water immersed for 7 days (37  degrees C) and
      thermocycled 10,000 times before the shear bond strength test (n = 10). The
      mercapto silane systems (SPS + MPS) were found to show superior resin bonding
      durability to the commercial primers and the only DHP-containing primer,
      regardless of additional incorporation of the phosphate monomer.

PMID- 29448580
TI  - Acrolein Production by Gas-Phase Glycerol Dehydration Using PO4/Nb2O5 Catalysts.
AB  - In this study, modified niobium oxide were prepared to study the addictive
      effects on the catalytic performance for gas-phase glycerol dehydration. The
      catalysts were characterized by N2 adsorption/desorption, XRD, NH3-TPD, FT-IR.
      The amount of phosphoric acid was up to 50 wt% in niobium. As a result, the
      highest glycerol conversion was achieved over 20 wt% PO4/Nb2O5. It indicates that
      the optimal amount of phosphoric acid leads the catalyst to have appropriate
      acidity which is an important factor for gas-phase glycerol dehydration.

PMID- 29448581
TI  - Arsenic Removal of Filters by Heat Treated Mixtures of Yellow Loess and Sand in
      One-Dimensional Column for Real Groundwater Treatment.
AB  - It is described that the arsenic (As) removal in real groundwater by filters in
      one-dimensional (1D) column (30 mm diameter * 240 mm height) using mixtures of
      heat treated yellow loess (YL) and sand is applied with consideration of water
      permeability. The effluent satisfies the concentration of <10 ppb drinking water
      regulation before As saturation with filters. Heat treated mixture of YL and sand
      under 4% H2/96% Ar condition result in higher As removal capacity than heat
      treated one under air atmosphere condition at 500  degrees C for 3 hours. It is
      due to more evolution of Fe3O4 phase in the mixture. In order to increase As
      removal efficiency significantly, alpha-Fe2O3 coated filters on mixture of YL and
      sand by hydrothermal treatment at 100  degrees C for 12 hours are utilized. It
      leads to highly enhanced As removal efficiency with little Fe ions leaching but
      half reduction of effluent rate, appealing as an alternative of practical As
      removal filters.

PMID- 29448582
TI  - Synthesis of Carbon Quantum Dots from Jujubes for Detection of Iron(III) Ions.
AB  - In this work, carbon quantum dots (CQDs) were synthesized from jujubes via a
      hydrothermal process. The as-prepared CQDs have average sizes of about 3.12 nm
      and emit blue photoluminescence (PL) in the range 380-530 nm, depending on the
      excitation wavelength. The functional group compositions and structures of the
      CQDs were investigated via Fourier transform infrared spectroscopy and X-ray
      powder diffraction. Based on these analyses, a linear relationship was obtained
      between the relative fluorescence intensity and concentration of Fe3+ within the
      range of 0 to 200 MUM (R2 = 0.9927). Fe3+ quenched the PL intensity of the CQDs
      more than other heavy metals, which indicates that CQDs can be used effectively
      as an Fe3+ sensing media.

PMID- 29448583
TI  - Preparation of Fe-Carbon Nanocomposite by Pyrolyzing Fe Adsorbed 1,8
      Diamminonaphthalene for the Adsorption of Cr (VI).
AB  - In the present work, a facile method for the preparation of nanocomposite
      adsorbents composed of carbon and iron compounds was demonstrated. The adsorbents
      were produced by pyrolyzing an iron-coordinated 1,8-diaminonaphthalene at various
      temperatures under an N2 stream (FeDN X, where X represents the pyrolysis
      temperatures 600, 700, and 800  degrees C). Prepared FeDNs were employed as
      adsorbents for the removal of Cr (VI). The Cr (VI)-adsorption behavior of FeDNs
      were well-fitted to a Langmuir isotherm model. Among the samples prepared, FeDN
      700 showed the best performance for the removal of Cr (VI). In particular, the
      maximum adsorption capacity of FeDN 700 was evaluated to be 34.81 mg/g. A variety
      of characterizations were carried out to elucidate the relationship between
      physical properties of adsorbents and their adsorption behaviors.

PMID- 29448584
TI  - Field Emission and Electrical Properties of Perovskite.
AB  - We investigate characteristic field emission properties of methyl ammonium mixed
      halide perovskite (CH3NH3PbI3-xClx) and their current change under one laser
      pulse. To analyze these properties, we fabricated inverted-type mixed-halide
      perovskite solar cells which exhibit a device efficiency of 9.31% under A.M 1.5
      condition. Under one laser pulse varying from 420 nm to 580 nm, perovskite layer
      considerably reacted from 420 nm to 440 nm and then gradually decreased in
      current. A turnon field of 5.56 V and a field enhancement factor of 3183 were
      obtained from one spin-coating perovskite layer and in eight times of perovskite
      spin-coating cycles, a turn-on field of 6.70 V and a field enhancement factor of
      5110 were observed.

PMID- 29448585
TI  - Hydrodeoxygenation of Pyrolysis Bio-Oil Over Ni Impregnated Mesoporous Materials.
AB  - The catalytic hydrodeoxygenation (HDO) of bio-oil over Ni-supported mesoporous
      materials was performed using a high pressure autoclave reactor. The actual
      pyrolysis oil of cork oak wood was used as a sample, and Ni/Al-SBA-15 and Ni/Al
      MSU-F were used as catalysts. In addition, supercritical ethanol was added as
      solvent. Both Ni-supported mesoporous catalysts showed efficient HDO reaction
      ability. A higher heating value and pH of bio-oil were achieved by the HDO
      reaction over both catalysts and upgraded bio-oil had a lower viscosity. Compared
      to Ni/Al-MSU-F, Ni/Al- SBA-15 produced more upgraded bio-oil with a lower oxygen
      content and higher heating value via a catalytic HDO process.

PMID- 29448586
TI  - New Yellow Synergist for Stable Pigment Dispersion of Inkjet Ink.
AB  - Minimizing ink droplet and self-dispersed pigment mixture are becoming hot issues
      for high resolution of inkjet printing. New synergist including sulfonic acid
      group of PY-74 was suggested and synthesized. Pigment itself did not show water
      solubility but new synergist, SY-11 exhibited good solubility in water and
      organic solvents such as DMSO and DMF. When aqueous pigment ink was prepared with
      SY-11, storage stability of the ink has been remained for 7 days under
      periodically repeated heating and cooling conditions. Particle size of formulated
      ink was around 150 nm.

PMID- 29448587
TI  - Droplet-Based Microfluidic Reactor for Synthesis of Size-Controlled CdSe Quantum
      Dots.
AB  - CdSe quantum dots (QDs) with a uniform size distribution were synthesized using a
      droplet-based microfluidic reactor. The droplet-based microfluidic reactor
      enabled continuous production of CdSe QDs at a temperature of less than 250 
      degrees C in an extremely shorter reaction time (less than 30 s) when compared
      with the batch reactor. The photoluminescence (PL) and ultraviolet (UV)
      absorption spectra of the CdSe QDs were recorded at different reaction times and
      the size and optical properties of the QDs were discussed. The structure
      morphology and elemental composition of the CdSe QDs were determined using a
      transmission electron microscopy (TEM) and electrondispersive spectroscopy (EDS).
      The size of CdSe QDs prepared using the microfluidic reactor was estimated to be
      from 1.6 to 2.6 nm with an average size of 2.2 nm. This droplet-based
      microfluidic reactor has the potential to be automated system continuous
      synthesis of CdSe QDs.

PMID- 29448588
TI  - Electrochemical Performance of FeSb2-P@C Composites as Anode Materials for
      Lithium-Ion Storage.
AB  - We have synthesized a novel composite material, FeSb2 alloy with red phosphorus
      (P) dispersed in a conductive carbon matrix, using high-energy ball milling
      (HEBM). The introduction of red P into FeSb2 alloy led to a formation of Sb phase
      along with FeSb2 phase due to the difference of binding energy between the
      elements. The morphology and structure were analyzed by transmission electron
      microscopy (TEM) and X-ray diffraction (XRD). The active components (Sb and P)
      react with Li+ ions while inactive element (Fe) and carbon matrix act as a metal
      framework to support the electrochemically active Sb and as a buffer to reduce
      volume change during cycling, respectively. Among electrodes (FeSb2, FeSb2-P,
      FeSb2-P@C), the FeSb2-P@C electrode demonstrated high reversible capacity of 400
      mAh g-1 with a good capacity retention of ~68% at 50 cycles and high rate
      reversible capacity of ~470 mAh g-1 at a current rate of 3000 mA g-1.

PMID- 29448589
TI  - Photocurrent Enhancement of CdSe Quantum-Dot Sensitized Solar Cells Incorporating
      Single-Walled Carbon Nanotubes.
AB  - We demonstrate quantum-dot sensitized solar cells (QDSSCs) which have colloidal
      CdSe quantum dots (TOPO-CdSe) as a sensitizer onto mesoporous TiO2 photoanodes.
      CdS quantum-dot (QD) layer plays a role of buffer layer for direct adsorption of
      TOPO-CdSe. We incorporate single-walled carbon nanotubes with TiO2 photoanode of
      our QDSSCs to facilitate efficient charge transfer. Shortcircuit current
      densities (Jsc) of our QDSSCs are enhanced while other parameters are maintained.
      Furthermore, we apply inert N2 pressure onto our sensitized photoanodes and
      observe 44% of Jsc enhancement with respect to pristine sample. Consequently,
      light-harvesting efficiency of our QDSSCs are increased. Significant series
      resistance reduction is observed from electrochemical impedance spectroscopy,
      indicating better interface contact between TiO2 photoanode and TOPOCdSe QD
      sensitizer are achieved.

PMID- 29448590
TI  - Catalytic Pyrolysis of Korean Pine (Pinus koraiensis) Nut Shell Over Mesoporous
      Al2O3.
AB  - The catalytic pyrolysis of waste Korean pine nut shell (KPNS) over mesoporous
      Al2O3 was investigated by thermogravimetric analysis (TGA) and pyrolyzer-gas
      chromatography/mass spectrometry (Py-GC/MS). TGA results showed that the thermal
      and catalytic pyrolysis of KPNS over mesoporous Al2O3 has the same decomposition
      temperature. On the other hand, the maximum decomposition for the catalytic
      pyrolysis of KPNS over commercial-Al2O3 shifted to a higher temperature. The Py
      GC/MS results indicated that large amounts of oxygen-containing pyrolyzates, such
      as acids, furans, levoglucosan, and phenols, were produced by the non-catalytic
      pyrolysis of KPNS. These oxygen-containing pyrolyzates were upgraded efficiently
      into aromatic hydrocarbons by applying Al2O3 catalysts. Between the two Al2O3
      catalysts, mesoporous Al2O3 showed better performance on the formation of
      aromatic hydrocarbons via the catalytic pyrolysis of KPNS than commercial Al2O3
      because of its uniform larger pores.

PMID- 29448591
TI  - Synthesis of Hollow Iron Oxide Nanospheres and Their Application to Gas Sensors.
AB  - Hollow nanomaterials have attracted great interest because of their many
      applications in catalysis, nanoreactors, drug delivery systems, for lubrication
      and in gas sensors. Here, carbon sphere templates were prepared from glucose
      under hydrothermal conditions to facilitate the synthesis of hollow Fe2O3
      nanospheres. Thermal decomposition of an iron precursor in benzylalcohol with the
      carbon spheres resulted in the deposition of Fe3O4 nanoparticles on the carbon
      sphere templates. The nanoparticles on the carbon surface naturally agglomerate
      and form a dense oxide shell during the calcination step, which produces typical
      Fe2O3 hollow structures. The gas sensing performance of the hollow Fe2O3
      nanospheres was investigated at an operating temperature of 300  degrees C. The
      hollow Fe2O3 nanospheres showed high sensitivity (R = 10.766 at 1 ppm
      formaldehyde) with a linear response to formaldehyde gas concentration in the
      range of 0.8~2.4 ppm, and good selectivity to formaldehyde gas in volatile
      organic compounds, compared to commercial Fe2O3 nanoparticles.

PMID- 29448592
TI  - Comparative Study of Hydrogel-Based Recyclable Photocatalysts.
AB  - A series of hydrogen-based TiO2 photocatalysts were prepared by the simple
      entrapment of TiO2 nanoparticles in different hydrogel matrices using gelation
      processes. The hydrogels, namely, agarose, alginate, and chitosan, were used as
      matrices for TiO2 immobilization. Morphological differences were characterized
      for the three different hybrid gel photocatalysts. The rate of methylene blue
      (MB) photodegradation increased with increasing initial TiO2 dosage in all
      samples. The structural properties of the hydrogels significantly affected the
      diffusion of MB and altered the photocatalytic activities. Among these three
      different hybrid gel photocatalysts, the chitosan-based TiO2 membrane showed
      superior activity to the agarose- and alginate-based TiO2 hybrid gels. In
      addition, chitosan/TiO2 still showed excellent photocatalytic activity after
      being reused in three cycles, suggesting that chitosan/TiO2 is a new potential
      eco-friendly and a cost-effective photocatalyst for wastewater treatment.

PMID- 29448593
TI  - Effect of Applied Current Density on Cavitation-Erosion Characteristics for
      Anodized Al Alloy.
AB  - Surface finishing is as important as selection of material to achieve durability.
      Surface finishing is a process to provide surface with the desired performance
      and features by applying external forces such as thermal energy or stress. This
      study investigated the optimum supply current density for preventing from
      cavitation damages by applying to an anodizing technique that artificially forms
      on the surface an oxide coating that has excellent mechanical characteristics,
      such as hardness, wear resistance. Result of hardness test, the greater hardness
      was associated with greater brittleness, resulting in deleterious
      characteristics. Consequently, under conditions such as the electrolyte
      concentration of 10 vol.%, the processing time of 40 min, the electrolyte
      temperature of 10  degrees C, and the current density of 20 mA/cm2 were
      considered to be the optimum anodizing conditions for improvement of durability
      in seawater.

PMID- 29448594
TI  - Conduction Mechanisms in Polyvinyl Alcohol: CdS/CdS:Cu Nanoparticle Hybrid
      Nanocomposites.
AB  - The electrical conduction mechanisms were investigated for the CdS and Cu-doped
      CdS (CdS:Cu) nanoparticles embedded in polyvinyl alcohol (PVA) (PVA/CdS and
      PVA/CdS:Cu) nanocomposites; synthesized by the chemical Sol Gel method on indium
      tin-oxide (ITO) substrate. X-ray diffraction pattern results show that the
      PVA/CdS nanocomposite is hawleyite-sturcture and PVA/CdS:Cu nanocomposites show
      greenockite-hawelyite mixed structure. The sizes of CdS and CdS:Cu nanoparticles
      were estimated from transmission electron microscopy (TEM) images and are ~4 nm
      and ~10 nm respectively; which were formed inside the PVA polymer layer. The
      devices were fabricated with Ag and ITO as electrodes with PVA/CdS and PVA/CdS:Cu
      nanocomposites as an active layers. The current-voltage (I-V ) relationships
      measurements shows the nature is extended memrisitve features for both PVA/CdS
      and PVA/CdS:Cu nanocomposites. The ION/IOFF ratios are enhanced and become more
      prominent in case of PVA/CdS:Cu nanocomposites device. The resistive switching
      characteristic show Schottky, Trapped-charge limited current (TCLC) and Space
      charge limited conduction (SCLC) mechanisms in Ag/PVA/CdS/ITO device; whereas
      Schottky, Ohmic, TCLC and SCLC were observed in Ag/PVA/CdS:Cu/ITO device.

PMID- 29448595
TI  - Nanostructured Titania Templated by Natural Cellulose Substance: Effect of
      Vanadium-Doping on the Anatase-to-Rutile Phase Transformation.
AB  - Vanadium-doped rutile titania nanomaterial was synthesized by calcination of
      titania/vanadia composite thin gel films pre-coated natural cellulose substance
      (e.g., ordinary filter paper) at a relatively low temperature (600  degrees C). A
      better mixture of titanium and vanadium species is achieved during the layer-by
      layer (LbL) deposition process with cellulose nanofiber as a template, leading to
      more vanadium dopants incorporated in the titania crystal lattices. By sufficient
      vanadium-doping, the phase transformation temperature from anatase to rutile
      phase of titania is decreased effectively. The doping mode and existing state of
      vanadium in the titania nanomaterials and the effect on the anatase-to-rutile
      phase transformation have been studied. This strategy provides a facile and
      effective route to facilitate the phase transformation of various nanostructured
      metal oxides templated by natural cellulose substance through doping appropriate
      functional metal ions in the LbL deposition process.

PMID- 29448596
TI  - Enhanced Power Factor and Increased Conductivity of Aluminum Doped Zinc Oxide
      Thin Films for Thermoelectric Applications.
AB  - We report the structural, electrical and thermopower properties of un-doped and
      Al doped zinc oxide (ZnO) thin films. Al doping was carried out using 25 keV Al+
      implantation with 0.1, 1 and 2% Al into ZnO. X-ray diffraction measurements
      showed that the lattice parameters were larger than the bulk values, which is
      consistent with the incorporation of Al atoms at interstitials. Al doping
      increased the electrical conductivity from 100 (Omegacm)-1 in the un-doped ZnO
      film to 598 (Omegacm)-1 in the 2% Al doped ZnO film. Electron doping by Al
      resulted in an increase in the carrier concentration and it had an advantageous
      effect on the mobility where it was highest for 2% doping. The absolute value of
      the Seebeck coefficient systematically increased for un-doped, 1% and 2% Al doped
      ZnO films where the room temperature values were -50.8, -60.9 and -66.3 MUV/K,
      respectively. The power factor increased significantly from 2.58 * 10-5 W/mK2 in
      un-doped ZnO film to 2.63 * 10-4 W/mK2 in 2% Al doped ZnO film. Our results
      suggest that the ion beam method is a suitable technique to enhance the
      thermoelectric properties of ZnO.

PMID- 29448597
TI  - Enhanced Catalytic Activity, Facile Synthesis and Characterization Studies of
      Spinel Mn-Co Aluminate Nano-Catalysts.
AB  - Undoped and Mn2+ doped CoAl2O4 (MnxCo1-xAl2O4; x = 0.0 to 1.0) spinel
      nanoparticles were successfully synthesized by a microwave heating method using
      glycine as the fuel. X-ray powder diffraction (XRD) was confirmed the cubic
      spinel structure. The average crystallite size of the samples was found to be in
      the range of 16.46 nm to 20.25 nm calculated by Scherrer's formula. The nano
      sized particle-like morphology of the samples was confirmed by high resolution
      scanning electron microscopy (HR-SEM) and transmission electron microscopy (HR
      TEM) analysis. Energy dispersive X-ray (EDX) results showed the pure form of
      spinel aluminate structure. The band gap energy (Eg) of pure CoAl2O4 was
      estimated to be 3.68 eV from UV-Visible diffuse reflectance spectroscopy (DRS),
      and the Eg values increased with increase of Mn2+ ions, due to the smaller grain
      size. The magnetic hysteresis (M-H) loop showed the superparamagnetic nature, and
      the magnetization and coercivity values increased with increasing Mn2+ ions,
      which was confirmed by vibrating sample magnetometer (VSM). All compositions of
      the nano-catalysts were tested as catalyst successfully for the conversion of
      benzyl alcohol into benzaldehyde and observed good catalytic activity.

PMID- 29448598
TI  - Effect of Porous Structure and Acidity of ZSM-5/SBA-15 Catalyst on 1,3,5
      Triisopropylbenzene Cracking Catalytic Activity.
AB  - ZSM-5/SBA-15 composite materials with different acidities and mesoporous system
      formations were successfully synthesized by three-step method. The catalysts were
      characterized by XRD, HR-TEM, BET, EDX and TPD-NH3 methods. It showed that the
      Si/Al molar ratio had effect on the formation and property of materials. Among
      synthesized catalysts with the different Si/Al molar ratios of 30 (HZSC-30), 50
      (HZSC-50), 70 (HZSC-70), HZSC-50 catalyst had better mesoporous system formation
      and acidity. These properties helped this catalyst to have higher catalytic
      activity in 1,3,5-triisopropylbenzene cracking reaction than other studied
      catalysts in term of higher benzene product yield. In comparison to HZSM-5
      microporous material that had the similar Si/Al molar ratio of 50, it showed that
      the formation of mesopore system of HZSC-50 catalyst had a major improvement on
      the cracking catalytic activity.

PMID- 29448599
TI  - Hydroxyapatite Coating on TiO2 Nanotube by Sol-Gel Method for Implant
      Applications.
AB  - The aim of this study was to determine the effect of hydroxyapatite (HA) coating
      on titanium dioxide (TiO2) nanotube by sol-gel process on viability of osteoblast
      like cell (MC3T3-E1) and bone formation in rat tibia. Specimens were divided into
      three groups including commercially pure titanium (control group), TiO2 nanotubes
      (group N), and HA coated TiO2 nanotubes (group HN). Surface characteristics were
      determined using field emission scanning electron microscope (FE-SEM; S-4700,
      Hitachi, Japan) and contact angles were measured. Cell viability was investigated
      in vitro after 1 day, 3 days, and 7 days of incubation. Implants (2.0 mm in
      diameter and 5.0 mm in length) were inserted into the tibia of rats. After 4
      weeks, histomorphometric analysis was performed. Both N and HN groups showed
      enhanced hydrophilicity compared to control group. After 7 days of implantation,
      group HN showed higher cell viability with marginal significance (0.05 < P <
      0.1). Bone to implant contact (BIC) ratio in the control group, group N, and
      group HN were 32.5%, 33.1%, and 43.8%, respectively. Results of this study showed
      that HA coated TiO2 nanotube using sol-gel process could be used to enhance
      hydrophilicity and improve osseointegration of dental implant surface.

PMID- 29448600
TI  - Effects of Aging on Transformation of Biogenic Magnetite Nanoparticles.
AB  - This study examined the microbial synthesis of magnetite and Pd/Zn-substituted
      magnetite using metal-reducing bacteria (Clostridium sp.), and the mineralogical
      characteristics of various types of magnetite formed initially and transformed
      minerals aged for 5 years. XRD, SXRD, and TEM-EDS analyses were used to
      characterize the mineralogy, crystal structure, chemistry, shape, and size
      distribution of the magnetites and transformed minerals. The metal-reducing
      bacteria reduced akaganeite and Pd/Zn-akaganeite to magnetite and Pd/Zn
      substituted magnetite using glucose as an electron donor, respectively. Metal
      substitution of Pd and Zn within the magnetite structure resulted in a decrease
      in the unit-cell parameter of the magnetite crystals. After 5 years, the biogenic
      magnetite showed changes in unit-cell parameters and transformation to siderite
      during prolonged cultivation under anaerobic conditions. These results indicate
      that long-term aging may affect the mineralogical transformation and alter the
      nano-sized crystal structure.

PMID- 29448601
TI  - Probing Amyloid beta and the Antibody Interaction Using Atomic Force Microscopy.
AB  - Amyloid beta (Abeta) peptide is considered to be the critical causative factor in
      the pathogenesis of Alzheimer's disease (AD) because the hydrophilic molecules
      accumulated outside of the neural cells and results in the formation of highly
      toxicity amyloid plaque. In this study, we probed the interaction between Abeta
      and the antibody using atomic force microscopy (AFM). We compared two kinds of
      antibodies which are the antibody for Abeta 1-42 (antibody42) and the antibody
      for Abeta 1-16 (antibody16). To detect the interaction between Abeta and the
      antibodies, the single molecular force spectroscopy was carried out using Abeta
      modified glass substrate and the antibodies modified AFM probes. In the results,
      the single Abeta-antibody42 dissociation constant was estimated to be 5.2 * 10-3
      s-1 and the single Abeta-antibody16 dissociation constant was 2.8*10-2 s-1. The
      Abeta-antibody42 showed 5.3 times longer bond life time compare with Abeta
      antibody16. It suggested that antibody42 is better choice for the Abeta sensor
      development.

PMID- 29448602
TI  - Preparation of Silica Coated Magnetic Nanoparticles for Bioseparation.
AB  - Magnetic nanoparticles have been intensively developed and applied in several
      biomedical applications such as targeted delivery, drug therapy, hyperthermia,
      magnetic resonance imaging and bioseparation etc. This work describes a simple
      and convenient method to synthesize silica coated Fe3O4 nanoparticles which have
      the potential to be used in the bioseparation of fetuin from fetal bovine serum
      and albumin from the egg. In this work, uniform Fe3O4 particles were prepared
      through the one-pot solvothermal process at 200  degrees C for 12 h using a sole
      iron precursor (FeCl3 . 6H2O) and then were coated with SiO2 to prepare silica
      coated Fe3O4 nanoparticles by hydrolysis and condensation of tetraethyl
      orthosilicate in ethanol and H2O medium. We further characterized the synthesized
      Fe3O4 and Fe3O4@SiO2 using XRD, SEM, TEM, FT-IR and VSM to study phase purity,
      morphology, size, functionality and magnetic properties.

PMID- 29448603
TI  - Selective Production of p-Xylene from Dimethylfuran and Ethylene Over Tungstated
      Zirconia Catalysts.
AB  - p-Xylene (PX) is an important large-volume commodity chemical in the
      petrochemical industry. Therefore, research on producing PX from bio-mass-derived
      resources is a considerable interest in relation to future alternative
      technologies. Recently, a new potential route for the direct and selective
      production of bio-based PX was reported, referred to as the Diels-Alder
      cycloaddition of biomassderived 2,5-dimethylfuran (DMF) and ethylene followed by
      the dehydration of an intermediate. Here, we prepared tungstated zirconia (WOx
      ZrO2) materials at different calcination temperatures and times as solid acid
      catalysts for PX production. From structural analyses and measurements of the
      surface acidity, the WOx-ZrO2 was found to be composed of mesopores with high
      surface acidity within the optimum calcination temperature and time range. This
      WOx-ZrO2 catalyst exhibited high catalytic activity upon the cycloaddition of DMF
      with ethylene as compared to commercial beta zeolite and previously reported
      silica-alumina catalysts.

PMID- 29448604
TI  - Catalytic Pyrolysis of Organosolv and Klason Lignin Over Al-SBA-15.
AB  - The catalytic pyrolysis of two types of lignin, organosolv and klason lignin,
      which were extracted from miscanthus, over Al-SBA-15 was carried out using a
      thermogravimetric (TG) analyzer and a pyroyzer-gas chromatography/mass
      spectrometry (Py-GC/MS). Although Al-SBA-15 has weak acidity, the large molecular
      phenolic pyrolyzates of lignin were converted effectively into small molecular
      phenols and aromatic hydrocarbons due to the large pore size of Al-SBA-15.
      Compared to klason lignin, organosolv lignin produced larger amounts of valuable
      chemicals, such as mono-phenol, mono-aromatics, and furans, by catalytic
      pyrolysis over Al-SBA-15.

PMID- 29448605
TI  - Preparation of Mesoporous CuCe-Based Ternary Metal Oxide by Nano-Replication and
      Its Application to Decomposition of Liquid Monopropellant.
AB  - Mesoporous CuCe-based ternary metal oxides were synthesized using KIT-6 as a hard
      template through a nano-casting method. The mesoporous CuCe-based metal oxides
      were applied to the catalytic decomposition of the ammonium dinitramide-based
      liquid monopropellant. The decomposition onset temperature over the meso-CuCe
      ternary metal oxides was much lower than that over the CuCeOx catalyst prepared
      by conventional precipitation method. Higher activity of the meso-CuCe ternary
      metal oxides is attributed to higher surface area and larger pore size of the
      meso-CuCe ternary metal oxides than those of the conventional CuCe oxide. The
      highest activity of meso-CuCeZr catalyst among the meso-CuCe ternary metal oxide
      catalysts is likely due to the highest mesoporosity.

PMID- 29448606
TI  - Study on Surface Damage and Performance Degradation of Impregnated Catalyst in
      Dielectric Barrier Discharge Plasma-Assisted Methane Conversion Processes.
AB  - This paper describes the performance degradation of impregnated catalyst in the
      dielectric barrier discharge (DBD) plasma-assisted methane conversion process. Mn
      and Ni mixed copper-zinc catalysts, and bare gamma-Al2O3 support were exposed to
      the DBD plasma generated at 1 kHz and 9 kV under CH4 direct conversion for 4
      hours. The performance degradation due to the surface damage of the catalyst by
      the plasma was investigated by SEM analysis.

PMID- 29448607
TI  - In-Situ Immobilization of Ni Complex on Amine-Grafted SiO2 for Ethylene
      Polymerization.
AB  - The results on the In-Situ synthesis of Ni complex on amine-grafted SiO2 and its
      ethylene polymerization were explained. SiO2/2NS/(DME)NiBr2 and
      SiO2/3NS/(DME)NiBr2(Ni(II) bromide ethylene glycol dimethyl ether) catalysts were
      active for ethylene polymerization. The highest activity was shown at the
      polymerization temperature of 25  degrees C, and SiO2/2NS/(DME)NiBr2 exhibited
      higher activity than SiO2/3NS/(DME)NiBr2. The PDI values of SiO2/2NS/(DME)NiBr2
      were in the range of 8~18. The aminosilane compounds and Ni were evenly grafted
      and distributed in the silica. It was proposed that DME ligand was mostly removed
      during the supporting process, and only NiBr2 was complexed with the amine group
      of 2NS based on the results of FT-IR and ethylene polymerization.

PMID- 29448608
TI  - Bone-Like Apatite Formation on the Plasma Electrolytic Oxidation-Treated Ti-6Al
      4V Alloy in Solution Containing Si and Mg Ions.
AB  - The bon-like apatite formation on the plasma electrolytic oxidation (PEO)-treated
      Ti-6Al-4V alloy in solution containing Si and Mg ions was studied using various
      experimental techniques. A Ti-6Al-4V ELI disk and implant was used as a substrate
      for PEO. A pulsed DC power supply was used to apply a potential of 280 V in the
      electrolyte for 3 min. To examine the bioactivity, the PEO films formed implant
      specimens were immersed in a simulated body fluid (SBF) for 12 h. PEO-treated
      surface has large micro-pores and small micro-pores, and 5 Mg/Si and 20 Mg/Si
      coated surfaces showed the more small micro-pores than that of CaP coated
      surface. The peaks of the anatase and the hydroxyapatite phases after SBF
      immersion shifted to the left as compared to before SBF immersion. Numbers of
      cells increased, as Mg content increased on the PEO treated surface. Bone-like
      apatite is well formed on the Mg and Si contained surface.

PMID- 29448609
TI  - Pore Shape Changes and Apatite Formation on Zn and Si Ion-Doped HA Films of Ti
      6Al-4V After Plasma Electrolytic Oxidation Treatment.
AB  - In this study, pore shape changes and apatite formation on zinc (Zn) and silicon
      (Si) ion-doped hydroxyapatite (HA) films of Ti-6Al-4V by plasma electrolytic
      oxidation (PEO) treatment has been investigated by several techniques. The PEO
      films and the Ti-6Al-4V surface after immersion in SBF were observed by X-ray
      spectroscopy, field-emission scanning electron microscopy, and energy dispersive
      X-ray spectroscopy. The number of pores decreased as Zn ion concentration
      increased from 5Zn to 10Zn. The maximum size of pores were increased from 5Zn to
      20Zn concentration, whereas, the minimum size of pores decreased. The amount of
      bone-like apatite formation for the 5Zn/5Si sample was higher than those of other
      samples immersed in SBF.

PMID- 29448610
TI  - Evaluation of the Fitness of Glass-Infiltrated Zirconia Core in Maxillary Central
      Incisor.
AB  - The purpose of this study was to evaluate the fitness of zirconia cores according
      to the amount and treated surface of glass infiltration. A maxillary right
      central incisor customized abutment was milled to have a 6 degrees  slope and a 1
      mm deep chamfer margin and was manufactured in an intaglio mold using silicone
      impression material. Fifty-six stone dies were produced by injecting high
      strength dental stone into a mold and then zirconia cores were milled with
      CAD/CAM systems. The control group (Control) used non glass-infiltrated zirconia,
      and the experiment group was divided by one with the glass and distilled water
      ratio of 1:300 and the other with the ratio of 1:100. Each group was divided into
      subgroups by glasstreated surface: external surface infiltration, internal
      surface infiltration, and both surface infiltration. The zirconia cores sintered
      after glass infiltration were attached to the stone dies and then cut.
      Afterwards, the absolute marginal discrepancies and internal gaps of the buccal
      and lingual sides were measured. The buccal absolute marginal discrepancies and
      lingual internal gaps were influenced by the glass infiltration amount (p <
      0.05); while fitness of zirconia core were not affected by the glasstreated
      surface (p > 0.05). As a result of the above experiments, the glass-infiltrated
      zirconia cores showed a clinically acceptable fitness, which is within 120 MUm.
      This means that glass infiltration can be clinically used.

PMID- 29448611
TI  - Electrochemical Deposition of Hydroxyapatite Substituted with Magnesium and
      Strontium on Ti-6Al-4V Alloy.
AB  - In the present study, electrochemical deposition of hydroxyapatite substituted
      with magnesium and strontium on Ti-6Al-4V alloy have investigated. Mg and Sr
      doped HAp was coated using subsequently pulsed electrochemical deposition process
      at 85  degrees C in the solution contained Ca, Mg, Sr, and P ion. The morphology
      of Mg/Sr-HAp formed on implant was investigated using scanning electron
      microscopy and X-ray diffraction. HAp grain size and XRD intensity decreased with
      Mg2+ and Sr2+ ions. The initial current density was changed with addition of Mg
      and Sr ion concentration when the constant voltage was applied to specimens. The
      morphologies and phase of HAp coated layers were affected by the Mg and Sr ion
      concentration. Results suggest that Mg/Sr-HAp layer formed on Ti can be a
      potential candidate for dental materials application.

PMID- 29448612
TI  - Morphology Changes of Plasma Electrolytic Oxidized Ti-6Al-4V Alloy in the
      Electrolytes Containing Sr and Si Ions.
AB  - In this study, morphology changes of plasma electrolytic oxidized (PEO) Ti-6Al-4V
      alloy in the electrolytes containing Sr and Si ions were researched using field
      emission scanning electron microscope, Image J program thin film X-ray
      diffraction, and energy dispersive X-ray spectroscopy. Pulsed DC power supplied
      Ti-6Al-4V alloy was used at a 280 V for 3 minutes in the electrolyte containing
      Sr and Si ions. To determine cell growth, human embryonic kidney cells 293 were
      grown at a density of 2 * 105 cells per 1.0 ml in well plates. The pore size
      decreased, as the content of Sr ion increased, whereas, the number of pores per
      area increased. The Ca/P ratio of PEO treated in electrolyte containing high Sr
      concentration showed the higher than those of in electrolyte containing low Sr
      concentration. The peak of HA is shifted to left side, as the concentration of Sr
      increased. Also, the number of cells increased, as the concentration of Sr
      increased.

PMID- 29448613
TI  - A Study on H2SO4-Treated MxOy Catalysts for Styrenated Phenols by Alkylation of
      Phenol with Styrene.
AB  - Styrenated phenols (SPs) involving very small amount of unreacted phenol and high
      content of di-SP (DSP) were synthesized, which can be used to prepare SP
      alkoxylate. The solid catalyst was prepared by impregnation method. SO2-4 on SO2
      4/MxOy catalyst was introduced from an aqueous 1M-H2SO4 solution. The catalysts
      were characterized by XRD patterns, and FT-IR spectra. The catalytic activity was
      examined by measuring conversion of phenol and styrene in a batch liquid-phase
      reactor. The concentration of phenol, styrene, and SPs were measured by GC with
      capillary column. The optimum synthesis conditions for concentration of sulfuric
      acid solution, catalyst amount of reactants, reaction temperature, and reaction
      time over SO2-4/ZrO2 catalyst were 15 wt%, 15 wt%, 100  degrees C, and 6 hr,
      respectively. At these conditions, conversion of both phenol and styrene were
      almost 100%, and the selectivity of DSP was 52.1%. On the other hand, the optimum
      synthesis conditions over SO2-4/TiO2 catalyst were 10 wt%, 5 wt%, 100  degrees C,
      and 1 hr, respectively, and conversion of both phenol and styrene were almost
      100%, and the selectivity of DSP was 66.1%.

PMID- 29448614
TI  - A Study on Synthesis of Styrenated Phenol Over Al . Ni/SiO2-Supported Catalysts.
AB  - Styrenated phenol was prepared by an alkylation of phenol using NiCl2 and AlCl3
      supported on silica gel. The conversion of phenol and styrene of alkylation
      reaction, and the selectivity of styrenated phenol were investigated. The Al .
      Ni/SiO2 Supported catalyst was used, the conversion of phenol was almost 100%.
      The product was in the form of a mixture of mono-styrenated phenol, di-styrenated
      phenol and tri-styrenated phenol. The styrenated phenol were selectivity of the
      varies depending on the reaction conditions.

PMID- 29448615
TI  - Synthesis of the Molybdenum Precursor for Slurry-Phase Hydrocracking of Heavy
      Oil.
AB  - In this study, Molybdenum precursors were synthesized with butanoic acid,
      hexanoic acid, nonanoic acid, decanoic acid, and undecanoic acid. In order to
      determine chemical structure of Synthesized molybdenum precursors, 1H(13C)-NMR,
      EA and ICP were used pyrolysis properties were measured TGA. The molybdenum
      precursors was used for Hydrocracking of Vacuum R1esidue (VR). It was shown that
      molybdenum nonanoate(3) was shown the lowerst Toluene Insoluble and Gas Product
      about 2.1 and 5.0 percent.

PMID- 29448616
TI  - Flame Retardant Effect of Nano Fillers on Polydimethylsiloxane Composites.
AB  - Polydimethylsiloxane has exceptional fire retardancy characteristics, which make
      it a popular polymer in flame retardancy applications. Flame retardancy of
      polydimethylsiloxane with different nano fillers was studied.
      Polydimethylsiloxane composite fire property varies because of the shape, size,
      density, and chemical nature of nano fillers. In house made carbon and bismuth
      oxide nano fillers were used in polydimethylsiloxane composite. Carbon from
      biochar (carbonised bamboo) and a carbon by-product (carbon soot) were selected.
      For comparative study of nano fillers, standard commercial multiwall carbon nano
      tubes (functionalised, graphitised and pristine) as nano fillers were selected.
      Nano fillers in polydimethylsiloxane positively affects their fire retardant
      properties such as total smoke release, peak heat release rate, and time to
      ignition. Charring and surface ceramization are the main reasons for such
      improvement. Nano fillers in polydimethylsiloxane may affect the thermal mobility
      of polymer chains, which can directly affect the time to ignition. The study
      concludes that the addition of pristine multiwall carbon nano tubes and bismuth
      oxide nano particles as filler in polydimethylsiloxane composite improves the
      fire retardant property.

PMID- 29448617
TI  - Microquantitation of Prostate-Speciflc Antigen by Using Antibody-Conjugated
      Magnetic Microsphere Beads.
AB  - Prostate-specific antigen (PSA) is a glycoprotein that is secreted by prostate
      gland epithelial cells, and elevation of PSA level in serum is often observed
      with prostate cancer or prostate disorders. Therefore, detection of PSA level in
      patient specimens is used as a diagnostic marker when screening of prostate
      cancer. In this study, we developed PSA antibody-conjugated microsphere beads
      that can be used for quantitation of PSA. We optimized the procedure for bead
      preparation and validated the detection analysis by using LNCaP and DU-145
      prostate cancer cell lysates. By applying the procedure, extracellular PSA from
      culture media of LNCaP cells and standard PSA proteins were quantified to assess
      whether the antibody-conjugated microsphere bead can be used to detect trace
      amounts of PSA. The PSA level results obtained by using the antibody-conjugated
      microsphere beads indicate that the procedure is sensitive and quantitative in
      analyzing PSA. Taken together, the results suggest that the method is suitable
      for microquantitation of PSA from patient specimens.

PMID- 29448618
TI  - Estrogenicity of Octyl Glucoside Synthesized by Direct Glucosidation as Non
      Endocrine Disruptive Surfactant.
AB  - The estrogenicity of octyl glucoside was studied with its preparation method
      using microporous zeolites. Its estrogenicity was estimated using E-assay method
      to confirm the possibility as non-endocrine disruptive surfactant. The octyl
      glucoside was synthesized from D-glucose with 1-octanol by direct glucosidation.
      The high conversion of D-glucose was obtained on H-FAU zeolite which has a mild
      acid strength. The conversion and yield were improved with increasing of acid
      site amount of the zeolite catalysts. The octyl glucopyranoside is more
      hydrophilic than nonylphenol and has a high wettability. The octyl glucosides
      represented extremely lower estrogenic cell proliferation compared with
      nonylphenol.

PMID- 29448619
TI  - Improved Dissolution and Oral Bioavailability of Celecoxib by a Dry Elixir
      System.
AB  - The purpose of this study was to develop and evaluate a dry elixir (DE) system
      for enhancing the dissolution rate and oral bioavailability of celecoxib. DE
      system has been used for improving solubility, oral bioavailability of poorly
      water-soluble drugs. The encapsulated drugs or solubilized drugs in the matrix
      are rapidly dissolved due to the co-solvent effect, resting in both an enhanced
      dissolution and bioavailability. DEs containing celecoxib were prepared by spray
      drying method and characterized by morphology, drug/ethanol content, drug
      crystallinity, dissolution rate and oral bioavailability. The ethanol content and
      drug content in DE system could be easily altered by controlling the spraydrying
      conditions. The dissolution profile of celecoxib from DE proved to be much higher
      than that of celecoxib powder due to the nano-structured matrix, amorphous state
      and encapsulated ethanol. The bioavailability of celecoxib from DEs was compared
      with celecoxib powder alone and commercial product (Celebrex(r)) in rats. In
      particular, blood concentrations of celecoxib form DE formulation were much
      greater than those of native celecoxib and market product. The data demonstrate
      that the DE system could provide an useful solid dosage form to enhance the
      solubility, dissolution rate and oral bioavailability of celecoxib.

PMID- 29448620
TI  - Characterization of Pt-Based Catalyst by Consecutive Experiments of Toluene
      Oxidation.
AB  - Catalytic oxidation of toluene was carried out to investigate the effect of
      consecutive run on the catalytic property and performance of 1 wt.% Pt/gamma
      Al2O3 and the reduced 1 wt.% Pt/gamma-Al2O3. The properties were characterized by
      X-ray diffraction (XRD), the Brunauer Emmett Teller (BET) surface area,
      temperature programmed reduction (TPR), and transmission electron microscopy
      (TEM) analyses. In consecutive experiments the second catalytic run resulted in a
      significant increase of the toluene conversion compared to the first catalytic
      run, but the toluene conversion in the third catalytic run was similar to that of
      the second catalytic run. In addition, the reducing treatment of the catalyst led
      to an increase in the catalytic activity. The increasing catalytic activity in
      consecutive runs was dependent on the platinum particle size and the oxidation
      state of the platinum. The increase in platinum particle size during reaction and
      the reduction in the oxidation state of platinum by hydrogen pretreatment were
      responsible for the increase in the catalytic activity.

PMID- 29448621
TI  - Removal of Food Waste Odor Using Nanoporous Carbon Adsorbents.
AB  - The removal of acetaldehyde, which is one of main components of food waste odor
      was investigated using biomass char as a nanoporous carbon absorbent. The biomass
      char adsorbent obtained from the pyrolysis of Geodae-Uksae was modified by the
      water and KOH treatment. The modified char absorbent had a higher acetaldehyde
      removal efficiency than nanoporous CMK-8 possibly due to its high oxygen and
      nitrogen functional groups.

PMID- 29448622
TI  - Asymmetric Bipolar Pulsed dc Sputtered Nanocrystalline VN Coatings for Electrode
      Materials in Lithium Battery.
AB  - Nanocrystalline vanadium nitride (VN) coatings for electrode materials for
      lithium battery with various deposition parameters have been prepared using dc
      and asymmetric bipolar pulsed dc magnetron sputtering. The deposition parameters
      such as pulse frequency and the duty cycle were varied from 0 to 50 kHz and 100
      to 75%, respectively. Microstructural, crystallographic and electrical
      characterizations were performed by FE-SEM, AFM, XRD and 4-point probe method.
      With an increase in pulse frequency, coating microstructure evolved from a porous
      columnar structure to a highly dense one. Single- phase cubic (FCC) VN coatings
      with different preferential orientations were obtained as a function of pulse
      frequency. Minimum resistivity of 108 MUOmega-cm was obtained for the coatings
      deposited at pulse frequency of 25 kHz.

PMID- 29448623
TI  - Asymmetric Bipolar Pulsed dc Sputtered Niobium Nitride Films for Electrode
      Materials in Supercapacitors.
AB  - Niobium nitride (NbN) films were deposited using asymmetric-bipolar pulsed dc
      sputtering at different pulse parameters. Microstructural, electrical and
      mechanical characterizations were performed by FE-SEM, AFM, LCR meter and
      nanoindentator. The results show that pulse frequency has significant effects on
      coating's microstructure, structural and electrical properties of NbN films. With
      an increase in pulse frequency, coating microstructure evolved from a porous
      columnar structure to a highly dense one. Average crystal grain sizes of NbN
      films were decreased from 52.7 nm to 27.5 nm with an increase in pulse frequency.
      The minimum resistivity of 351 MUOmega-cm, the smoothest surface morphology with
      Ra roughness of 0.4 nm and the maximum hardness of 17.4 GPa were obtained for the
      films deposited at pulse frequency of 50 kHz, respectively.

PMID- 29448624
TI  - Innovative Mesoporous Nanosilicas: SBR Nanocomposite for Low Environmental Impact
      Tread Tyre.
AB  - Silica nanoparticles with different aspect ratios (A.R.) were tested as
      reinforcing fillers of styrenebutadiene copolymer (s-SBR) for "green tyres,"
      i.e., tires with lower rolling resistance. A commercial nanosilica with A.R. = 1
      (Aerosil(r) 200) was compared with two nanosilica samples with A.R. = 2 and 4,
      synthesized by means of an innovative process, to ascertain if the filler shape
      was significant to improve the composite properties. In addition, bis
      triethoxysilylpropyltetrasulfide was grafted onto the particles surface, in order
      to obtain more hydrophobic materials and to enhance their dispersion in the
      elastomeric composites: pristine and modified silicas were then compared.
      Grafting extent was evaluated by thermogravimetric analysis. The surface
      properties of silicas were investigated by Fourier transform infrared
      spectroscopy and inverse gas chromatography. s-SBR/silica nanocomposites were
      then prepared and characterized assessing their dynamic-mechanical properties and
      carrying out morphological observations by transmission electron microscopy.

PMID- 29448625
TI  - Aptamers-Based Sensing Strategy for 17beta-Estradiol Through Fluorescence
      Resonance Energy Transfer Between Oppositely Charged CdTe Quantum Dots and Gold
      Nanoparticles.
AB  - A novel aptamers-based fluorescence resonance energy transfer (FRET) assay was
      developed employing the oppositely charged thioglycolic acid-capped CdTe quantum
      dots (TGA-CdTe QDs) and cysteamine-stabilized gold nanoparticles (cysteamine
      AuNPs). The fluorescence of TGA-CdTe QDs was significantly quenched with addition
      of cysteamine-AuNPs via the FRET. The FRET process can be modulated by 17beta
      estradiol in that the specific recognition between 17beta-estradiol and aptamers
      could show different effects on the aptamers-mediated aggregation of cysteamine
      AuNPs, and correspondingly adjust the FRET process. The feasibility of the method
      has been demonstrated by carrying out the detection of 17beta-estradiol with the
      wide linear range from 0.5.ng mL-1 to 150 ng.mL-1 and the low detection limit of
      0.057 ng.mL-1. The established assay exhibited favorable selectivity towards
      17beta-estradiol over other endocrine disrupting compounds and probably
      coexisting chemicals in real samples. Furthermore, the assay has been
      successfully applied to detect 17beta-estradiol in real tap water samples and
      feeds samples with good performance. The results were in full consistence with
      those from HPLC method, indicating the reliability of the detection system. The
      aptamers-based FRET assay is expected to offer a new opportunity for the rapid
      analysis of 17beta-estradiol in real samples.

PMID- 29448626
TI  - Scaffolds Based on Collagen, Hyaluronan and Sericin with Potential Applications
      as Controlled Drug Delivery System.
AB  - Natural proteins have been extensively studied as matrices for tissue
      engineering, due to their excellent biocompatibility and biological properties
      associated with increasing cell proliferation. By generating complex materials,
      cell and tissue functions can be tailored to obtain a specific direction,
      according to the medical needs. The aim of this paper was to obtain scaffolds
      based on collagen, hyaluronan and sericin, with morphology and physical-chemical
      properties adequate for controlled drug delivery systems. In this aim various
      tests were performed: in vitro swelling and degradation studies, Fourier
      Transform Infrared spectroscopy (FT-IR), Scanning Electronic Microscopy (SEM) and
      thermogravimetric analysis. Loading and releasing of ibuprofen is also discussed.
      The results indicate that scaffolds based on collagen, hyaluronan and sericin
      have a porous structure, strength and stability adequate for skin tissue
      engineering. The obtained scaffolds swell, degrade and have controlled drug
      release properties in simulated biological fluids.

PMID- 29448627
TI  - Polysaccharide Functionalized Single Walled Carbon Nanotubes as Nanocarriers for
      Delivery of Curcumin in Lung Cancer Cells.
AB  - Nanoscale drug delivery systems have emerged as promising alternatives to
      overcome the problems associated with by conventional chemotherapy for cancer
      treatment such as poor drug stability and bio-distribution. Herein, we report a
      single walled carbon nanotubes (SWCNTs) based drug delivery system functionalized
      with polysaccharides such as alginate (ALG) and chitosan (CHI), which can be
      loaded with an anticancer drug curcumin (CUR). Modification of SWCNTs renders
      high drug loading efficiency and sustained drug release, imperative for drug
      activity. These were characterized through various tools viz, microscopic
      (transmission electron microscopy, scanning electron microscopy and atomic force
      microscopy) and zeta potential analysis. Incorporation of CUR inside the modified
      SWCNTs was studied through Fourier transform infrared spectroscopy, fluorescence
      and UV-visible spectroscopy. In vitro release studies were conducted to gain an
      insight into the pH-dependent release behavior of the entrapped CUR from modified
      SWCNTs. The anti-cancer potential was further demonstrated using human lung
      adenocarcinoma (A549) cells as a model system. Various cell culture based assays
      were performed to study the ability of released CUR from modified SWCNTs for
      inhibiting the cancer cell proliferation by inducing apoptosis.

PMID- 29448628
TI  - Functionalized Magnetic PLGA Nanospheres for Targeting and Bioimaging of Breast
      Cancer.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) are actively used as highly
      sensitive imaging probes to provide contrast in MRI. In this study, we propose
      the use of SPIONs encapsulated with antibody-conjugated poly(lactic-co-glycolic
      acid) (PLGA) as a potent theragnostic agent. The SPIONs were synthesized by a
      chemical co-precipitation method of ferric and ferrous ions, and subsequently
      encapsulated with PLGA by using an emulsification-diffusion method. Herceptin was
      chemically conjugated to the SPION-encapsulating PLGA nanoparticles to target the
      human epidermal growth factor receptor 2 (Her2/neu) overexpressing breast
      cancers. FACS and MR molecular imaging revealed that the Her2/neu overexpressing
      cell line showed a stronger contrast enhancement than the Her2/neu non-expressing
      cell lines, and the signal intensity of in vivo MR imaging decreased as the
      concentration of Herceptin increased. This strategy of encapsulating SPIONs with
      PLGA will be highly useful in functionalizing magnetic nanoparticles and
      improving the diagnostic and therapeutic efficacy of a wide array of cancer
      treatments.

PMID- 29448629
TI  - Synthesis and Characterization of Calcium Phosphate Ceramic/(Poly(vinyl alcohol)
      Polycaprolactone) Bilayer Nanocomposites-A Bone Tissue Regeneration Scaffold.
AB  - beta Tricalcium phosphate ceramic was used to reinforce nanofibers in composite
      mats produced via electrospinning of poly(vinyl alcohol) (PVA), polycaprolactone
      (PCL) and (PVA: PCL) bilayers. The role of TCP ceramic on morphology of
      nanocomposites, crystalline structure, functional groups and thermal behaviour of
      nanocomposites were characterized by SEM, EDAX, XRD, FTIR and DSC analysis.
      Ultrathin cross-sections of the obtained nanocomposites were morphologically
      investigated with SEM and all fabricated composites consisted of fibers with
      average fiber diameter (AFD) around 100 nm except PCL-TCP fibers having AFD in
      the range of 608 nm. XRD profile presented the main peaks of beta-TCP (JCPDS
      090169 and JCPDS 70-2065). The characteristic absorption bands of TCP were also
      identified by FTIR in all the composites. The thermal stability was enhanced
      after adding TCP filler particles in all the polymer composites. The porosity of
      PCL-TCP was found around 63% and (PVA-PCL: TCP) composite was found to be 58%.
      The biocompatibility of the (PVA-PCL: TCP) composite scaffold has also been
      investigated by culturing MG-63 osteoblast cells on it; primary results showed
      that the cells adhered and proliferated well on the composite scaffold.

PMID- 29448630
TI  - Dynamic and Depth Dependent Nanomechanical Properties of Dorsal Ruffles in Live
      Cells and Biopolymeric Hydrogels.
AB  - The nanomechanical properties of various biological and cellular surfaces are
      increasingly investigated with Scanning Probe Microscopy. Surface stiffness
      measurements are currently being used to define metastatic properties of various
      cancerous cell lines and other related biological tissues. Here we present a
      unique methodology to understand depth dependent nanomechanical variations in
      stiffness in biopolymers and live cells. In this study we have used A2780 and
      NIH3T3 cell lines and 0.5% and 1% Agarose to investigate depth dependent
      stiffness and porosity on nanomechanical properties in different biological
      systems. This analytical methodology can circumvent the issue associated with the
      contribution of substrates on cell stiffness. Here we demonstrate that by
      calculating 'continuous-step-wise-modulus' on force versus distance curves one
      can observe minute variation as function of depth. Due to the presence of
      different kinds of cytoskeletal filament, dissipation of contact force might vary
      from one portion of a cell to another. On NIH3T3 cell lines, stiffness profile of
      Circular Dorsal Ruffles could be observed in form of large parabolic feature with
      changes in stiffness at different depth. In biopolymers like agarose, depending
      upon the extent of polymerization in there can be increase or decrease in
      stiffness due variations in pore size and extent to which crosslinking is taking
      place at different depths. 0.5% agarose showed gradual decrease in stiffness
      whereas with 1% agarose there was slight increase in stiffness as one indents
      deeper into its surface.

PMID- 29448631
TI  - Effects of CdSe and CdSe/ZnS Core/Shell Quantum Dots on Singlet Oxygen Production
      and Cell Toxicity.
AB  - Four types of quantum dots (QDs) with varying emission wavelengths were
      synthesized in this study. The dots included CdSe and CdSe/ZnS core/shell QDs
      with short emission wavelengths of 540 nm and 560 nm, respectively, as well as
      CdSe and CdSe/ZnS core/shell QDs with longer emission wavelengths of 585 nm and
      595 nm, respectively. The ligands on the QD surfaces were exchanged with
      mercaptopropionic acid (MPA) to make them water-soluble. The efficiency of
      singlet oxygen (1O2) production from both CdSe and CdSe/ZnS core/shell QDs was
      highest at a QD concentration of 14 MUg/ml Singlet oxygen production from the
      CdSe QDs was higher than that with the CdSe/ZnS core/shell QDs after 1 h of
      LED470 irradiation. However, the singlet oxygen production of CdSe/ZnS core/shell
      QDs was much higher than that of CdSe QDs at concentrations above 14 MUg/ml. The
      cytotoxicities of both CdSe and CdSe/ZnS core/shell QDs were investigated using
      HeLa cells.

PMID- 29448632
TI  - MPEG-CS/Bmi-1RNAi Nanoparticles Synthesis and Its Targeted Inhibition Effect on
      CD133+ Laryngeal Stem Cells.
AB  - Previous studies have confirmed that CD133+ cells in laryngeal tumor tissue have
      the characteristics of cancer stem cells. Bmi-1 gene expression is central to the
      tumorigenicity of CD133+ cells. In this study, we tried to develop a new siRNA
      carrier system using chitosan-methoxypolyethylene nanoparticles (CS-mPEG-NPs)
      that exhibit higher tumor-targeting ability and enhanced gene silencing efficacy
      in CD133+ tumor stem cells. It is hoped to block the self-renewal and kill the
      stem cells of laryngeal carcinoma. The mPEG-CS-Bmi-1RNAi-NPs were synthesized and
      their characters were checked. The changes in invasion ability and sensitivity to
      radiotherapy and chemotherapy of CD133+Hep-2 tumor cells were observed after Bmi
      1 gene silencing. The mPEG-CS-Bmi-1RNAi-NPs synthesized in this experiment have a
      regular spherical form, a mean size of 139.70 +/-6.40 nm, an encapsulation
      efficiency of 85.21 +/- 1.94%, with drug loading capacity of 18.47 +/- 1.83%, as
      well as low cytotoxicity, providing good protection to the loaded gene, strong
      resistance to nuclease degradation and high gene transfection efficiency. After
      Bmi-1 gene silencing, the invasion ability of CD133+ cells was weakened. Co
      cultured with paclitaxel, the survival rates of CD133+Bmi-1RNAi cells were lower.
      After radiotherapy, the mean growth inhibition rate of CD133+/Bmi-1RNAi cells was
      significantly lower than CD133+ cells. In conclusion, the mPEG-CS nano-carrier is
      an ideal vector in gene therapy, while silencing the Bmi-1 gene can enhance the
      sensitivity of CD133+ tumor stem cells to chemoradiotherapy and abate their
      invasion ability.

PMID- 29448633
TI  - Copolymeric Micelles Loading Curcumin: Preparation, Characterization and In Vitro
      Evaluation.
AB  - Curcumin (Cur) has potent antitumor activity; however, its clinical use is
      limited due to its hydrophobicity and instability at physiological pH. In this
      work, Cur was incorporated into MPEG2K-P(CL-co-LLA) micelles to form the Cur
      loaded micelles with drug loadings from 4.72% to 35.21% depending on the ratios
      of drug to MPEG2K-P(CL-co-LLA). The resulting Cur-loaded micelles were spherical
      with mean hydrodynamic diameters in the range of 28.8 to 58.6 nm, having
      excellent water-solubility and good stability at pH 7.4. The freeze-drying
      powders of the Cur-loaded micelles were easily rehydrated. It was found that Cur
      was slowly released from the micelles with a cumulative drug release percentage
      of 78.11% within 14 days and there was no obvious drug burst release. MTT tests
      showed that, the IC50 values of the Cur-loaded micelles were lower than those of
      free Cur against cancer cells (MDA-MB-231 cells and 4T1 cells). No matter for
      cancer cells (MDA-MB-231 cells and 4T1 cells) or healthy cells (L929 cells), cell
      viabilities were all >90% after incubating with the blank MPEG2K-P(CL-co-LLA)
      micelles, even at very high micelle concentration (up to 1000 MUg/mL), indicating
      the blank micelles were of no or extremely low cytotoxicity per se. The Cur
      loaded micelles were taken up mainly via endocytosis route and the cellular
      uptake on 4T1 cells increased with incubation time. They could induce more cell
      apoptosis compared to free Cur. These results suggested that curcumin-loaded
      MPEG2K-P(CL-co-LLA) micelles may be a potential nanoscale drug delivery system
      for cancer therapy.

PMID- 29448634
TI  - Comparison of the Off-Target Effects Among One-Base to Three-Base Mismatched
      Targets of gRNA Using a Blue to White Assay.
AB  - The present study was designed to test a new strategy for comparing the off
      target effects of CRISPR/cas9 employing a blue/white colony based assay. Eight
      types of AmpR plasmids with matched, one base mismatched, two bases mismatched
      and three bases mismatched targets were constructed. The wild typed alpha peptide
      of the beta-glactosidase gene and some with mutations, chosen as the targets,
      were successfully subcloned into the plasmids in an inframe pattern. The relevant
      gRNA and cas9 were subcloned into the ChloR plasmid. Transformation of the
      plasmid harboring the target gene yielded blue colonies, while white colonies
      formed in the plates following the co-transformation of target gene plasmid and
      the CRISPR/cas9 plasmid. Colonies in different levels of blue color were formed
      from the plasmids having completely matched target and mismatched targets. The
      appearance of different blue levels following the co-transformation of the
      different target plasmid and CRISPR/cas9 plasmid qualitatively indicated the
      effectiveness of the gRNA, while the ratio of the AMP/CL colonies can be used for
      relatively quantitative evaluation. The target and off-target effects among
      different targets of gRNA were differentially identifiable and these effects in
      turn demonstrated the effectiveness of the blue to white assay. Either the
      qualitative or the quantitative analysis of the blue to white depends on the
      final interactions among the target, the cas9 and the gRNA. Clearly, when co
      transformation is replaced by single transformation using a specialized
      nanoparticle containing these three components, the target and off-target effect
      will be more accurately evaluated. Thus, this study provided a model for
      application of nanoparticle in gene editing studies.

PMID- 29448635
TI  - Surface Plasmon Resonance Aptamer Biosensor for Discriminating Pathogenic
      Bacteria Vibrio parahaemolyticus.
AB  - In this paper, whole-bacteria SELEX (WB-SELEX) strategy was adopted to isolate
      specific aptamers against Vibrio parahaemolyticus. Round selection for V.
      parahaemolyticus was conducted 11 rounds, including two negative selection
      rounds. It was determined through real-time PCR amplification and post-SELEX
      experiment. The selected aptmers had high binding property and specificity to V.
      parahaemolyticus. Of 28 aptamers tested, VPCA-apta#1 had the highest binding
      affinity compared to other aptamer candidates obtained. To detect V.
      parahaemolyticus, aptamer based SPR biosensor platform was constructed and
      pathogenic bacteria sensing was conducted in two steps. The first step was to
      construct 5'-biotinylated VPCA-apta#1 binding probe. The second step was to
      incubate V. parahaemolyticus and test microbes in functionalized SA sensor chip
      in parallel. Our platform showed significant activity for detecting and
      discriminating V. parahaemolyticus from other enteric species such as Escherichia
      coli, Listeria monocytogenes, Sigella sonnei, and Vibrio fischeri. This is the
      first report on the use of whole-SELEX to isolate DNA aptamers specific for V.
      parahaemolyticus. We demonstrated the feasibility of using aptamer platform for
      the detection of V. parahaemolyticus in various food supplies. It might be used
      in multiple points of care for diagnosing Vibriosis.

PMID- 29448636
TI  - Fabrication of Polydopamine Coating and Its Application in Glucose Sensor.
AB  - Polydopamine (PDA) film coatings are multifunctional substances because these
      coatings can adhere to nearly all known solid materials. The self-polymerization
      of dopamine in aqueous solution was investigated in this study; PDA films are an
      effective platform for further functionalization similar to the reduction of
      silver ions into silver nanoparticles (NPs). The films provide a new method to
      attach metal NPs on substrates. Through this simple method, glucose sensors based
      on this kind of Ag NPs/ITO exhibited a detection limit of about 10 MUM and
      presented a good sensitivity enough for real use (3-8 mM).

PMID- 29448638
TI  - Delivery of Abscisic Acid to Plants Using Glutathione Responsive Mesoporous
      Silica Nanoparticles.
AB  - An intracellular glutathione (GSH) responsive phytochemical delivery system based
      on thiol gated mesoporous silica nanoparticles (MSNs) was developed and tested on
      the model plant Arabidopsis thaliana. In the present study, monodispersed MSNs
      with particle diameters of ~20 nm and pore sizes of ~2.87 nm were synthesized and
      modified. Abscisic acid (ABA), a key phytohormone, was entrapped in the mesopores
      of MSNs and then the pore entrances of MSNs were covered with decanethiol
      gatekeepers through GSH-cleavable disulfide linkages. An in vitro release test of
      ABA from decanethiol gated MSNs proved that there was efficient loading and
      entrapment of phytochemicals in the absence of a GSH redox trigger. Most
      importantly, in planta experiments demonstrated that GSH-mediated release of ABA
      from the pores of MSNs significantly reduced the leaf stomatal aperture and
      inhibited water loss of treated plants. Moreover, compared with the usage of free
      ABA, the controlled release of the encapsulated phytohormone from MSNs markedly
      prolonged the expression of the ABA inducible marker gene (AtGALK2) and finally,
      improved the drought resistance ability of Arabidopsis seedlings under drought
      stress. Therefore, the concept of using short-chain molecules as gatekeepers to
      encapsulate biomolecules in MSNs was demonstrated. The application of MSNs with
      redox-responsive gatekeepers has been shown in this study to be a potential and
      efficient technique to deliver phytochemicals into plants and release them in a
      controllable fashion.

PMID- 29448637
TI  - Characteristics of Sodium Polyacrylate/Nano-Sized Carbon Hydrogel for Biomedical
      Patch.
AB  - Conductive hydrogels were prepared for biomedical patch in order to improve the
      electrical conductivity. Sodium polyacrylate and nano-sized carbon were mixed and
      fabricated by aqueous solution gelation process in various contents of nano-sized
      carbon with 0.1, 0.5, 1.0 and 2.0 wt%. Sodium polyacrylate/nano-sized carbon
      conductive hydrogels were investigated by molecular structure, surface morphology
      and electrical conductivity. The conductivity of the hydrogel/nano-sized carbon
      conductive hydrogel proved to be 10% higher than conductive hydrogel without nano
      sized carbon. However, it was founded that conductive hydrogels with nano-sized
      carbon content from 0.5 up to 2.0 wt% were remarkably decreased. This may be due
      to the non-uniform distribution of nano-sized carbon, resulting from agglomerates
      of nano-sized carbon. The developed hydrogel is intended for use in the medical
      and cosmetic fields that is applicable to supply micro-current from device to
      human body.

PMID- 29448639
TI  - Temperature Dependent Electron Transport Properties of Gold Nanoparticles and
      Composites: Scanning Tunneling Spectroscopy Investigations.
AB  - Scanning tunneling spectroscopy (STS) is used for investigating variations in
      electronic properties of gold nanoparticles (AuNPs) and its composite with
      urethane-methacrylate comb polymer (UMCP) as function of temperature. Films are
      prepared by drop casting AuNPs and UMCP in desired manner on silicon substrates.
      Samples are further analyzed for morphology under scanning electron microscopy
      (SEM) and atomic force microscopy (AFM). STS measurements performed in
      temperature range of 33  degrees C to 142  degrees C show systematic variation in
      current versus voltage (I-V) curves, exhibiting semiconducting to metallic
      transition/Schottky behavior for different samples, depending upon preparation
      method and as function of temperature. During current versus time (I-t)
      measurement for AuNPs, random telegraphic noise is observed at room temperature.
      Random switching of tunneling current between two discrete levels is observed for
      this sample. Power spectra derived from I-t show 1/f2 dependence. Statistical
      analysis of fluctuations shows exponential behavior with time width tau ~ 7 ms.
      Local density of states (LDOS) plots derived from I-V curves of each sample show
      systematic shift in valance/conduction band edge towards/away from Fermi level,
      with respect to increase in temperature. Schottky emission is best fitted
      electron emission mechanism for all samples over certain range of bias voltage.
      Schottky plots are used to calculate barrier heights and temperature dependent
      measurements helped in measuring activation energies for electron transport in
      all samples.

PMID- 29448640
TI  - Impact of Isolation and Immobilization Layers on the Electro-Mechanical Response
      of Piezoresistive Nano Cantilever Sensors.
AB  - In the last decade, piezoresistive nano cantilever sensors have been extensively
      explored, especially for chemical and biological sensing applications.
      Piezoresistive cantilever sensors are multi-layer structures with different
      constituent materials. Performance of such sensors is a function of their
      geometry and constituent materials. For a fixed material set, the pre-requisite
      for optimizing the performance of a composite piezoresistive cantilever sensor is
      careful geometrical design of its constituent layers. Even though, treatise
      encompasses various designs of such sensors, typically for computational
      simplicity the functional layers i.e., the isolation and immobilization layers
      are neglected in the modeling stages. In this paper, we elucidate the impact of
      the functional layers on the electro-mechanical response of composite
      piezoresistive nano cantilever sensors. Systematic and detailed computations are
      performed using theoretical models and numerical simulations. Results show that
      both the isolation and immobilization layers play a critical role in governing
      the sensor performance. Simulation results depict that compared to a sensor with
      an isolation layer of thickness 100 nm, a sensor without isolation layer has
      36.29% and 42.51% better deflection sensitivity and electrical sensitivity
      respectively. Furthermore, it is found that when an immobilization layer of
      thickness 40 nm is added atop the isolation layer, the deflection sensitivity and
      electrical sensitivity reduces by 12.98% and 15.83% respectively. Through our
      investigation it is shown that the isolation and immobilization layers not only
      play a vital role in determining the stability and electro-mechanical response of
      the sensor but their negligence in the design stages can be detrimental. Apart
      from investigating the impact of the immobilization layer thickness, to model the
      sensor closer to real time operational conditions, we have performed analysis to
      understand the impact of non-uniformity in the immobilization layer thickness and
      non-uniform surface stress loading on the electro-mechanical response of the
      sensor. Results and inferences obtained from this study will help NEMS engineers
      to optimize the performance of piezoresistive nano cantilever sensors and to
      design multi-layer cantilever platform structures for other transducers.

PMID- 29448641
TI  - Characterization of Lateral Structure of the p-i-n Diode for Thin-Film Silicon
      Solar Cell.
AB  - The lateral structure of the p-i-n diode was characterized for thin-film silicon
      solar cell application. The structure can benefit from a wide intrinsic layer,
      which can improve efficiency without increasing cell thickness. Compared with
      conventional thin-film p-i-n cells, the p-i-n diode lateral structure exploited
      direct light irradiation on the absorber layer, one-side contact, and bifacial
      irradiation. Considering the effect of different carrier lifetimes and
      recombinations, we calculated efficiency parameters by using a commercially
      available simulation program as a function of intrinsic layer width, as well as
      the distance between p/i or n/i junctions to contacts. We then obtained excellent
      parameter values of 706.52 mV open-circuit voltage, 24.16 mA/Cm2 short-circuit
      current, 82.66% fill factor, and 14.11% efficiency from a lateral cell (thickness
      = 3 MUm; intrinsic layer width = 53 MUm) in monofacial irradiation mode (i.e.,
      only sunlight from the front side was considered). Simulation results of the cell
      without using rear-side reflector in bifacial irradiation mode showed 11.26%
      front and 9.72% rear efficiencies. Our findings confirmed that the laterally
      structured p-i-n cell can be a potentially powerful means for producing highly
      efficient, thin-film silicon solar cells.

PMID- 29448642
TI  - Nanocomposite Membranes Comprising Crosslinked Polymer Blends of Poly(vinyl
      alcohol)/Poly(styrene sulfonic acid-co-maleic acid) and Fumed Silica
      Nanoparticles.
AB  - Nanocomposite polymer electrolyte membranes comprising a crosslinked polymer
      blend of poly(vinyl alcohol)/poly(styrene sulfonic acid-co-maleic acid) (PVA/PSSA
      co-MA) and fumed silica nanoparticles were prepared for direct methanol fuel cell
      (DMFC) applications. Silica nanoparticles could be incorporated well uniformly in
      the completely miscible system, which can form a three-dimensional network
      structure to achieve the enhancement of mechanical properties as well as the
      additional reduction of methanol permeability. The optimized proton
      conductivities and methanol permeability of the PVA/PSSA-co-MA membrane with
      silica nanoparticles of 10 wt.% were 0.0482 S cm-1 at room temperature and 5.78 *
      10-7 cm2 s-1 at the methanol concentration of 40% (w/w), respectively.

PMID- 29448643
TI  - Effect of Colloidal Medium on the Shelf-Life and Stability of Gold Nanorods
      Prepared by Seed-Mediated Synthesis.
AB  - Gold nanorods (GNRs) owing to their tunable longitudinal surface plasmon
      resonance in tissue transparent near infrared region have potential applications
      (like cancer imaging, surface enhanced Raman spectroscopy, cancer targeting, drug
      delivery and optical hyperthermia) in nanomedicine. Success of these
      diagnosis/therapy options depends on the plasmonic properties of gold nanorods,
      which are influenced by the interaction of GNRs with the colloidal medium. In
      this article, a systematic study is performed to evaluate the effect of colloidal
      medium on shelf life and stability of gold GNRs. As-synthesized GNRs are
      preserved in four aqueous media (deionized water, pluronic F-127, CTAB solution
      and growth solution) and their stability is investigated by closely monitoring
      the changes in the plasmonic signatures by UV-Visible spectroscopy and variation
      in hydrodynamic size by photon correlation spectroscopy for 30 days. As
      synthesized GNRs are most stable in deionized water followed by pluronic F-127,
      CTAB and growth solution. The vast difference in the colloidal stability of GNRs
      in different media is due to the differences in surface driven unzipping of gold
      in these aqueous media.

PMID- 29448644
TI  - Persistent Methyl Orange Degradation Ability of MgAl2O4:(Pr3+,Dy3+)/M-TiO2
      Luminescent Photocatalyst.
AB  - Metal ions (Cr, Ni, Co) doped titania (M-TiO2) coupled with the long after glow
      phosphor MgAl2O4:(Pr3+, Dy3+) particles were synthesized by the sol-gel method,
      with the best mass ratio of MgAl2O4:(Pr3+, Dy3+) to M-TiO2 as 4:6. MgAl2O4:(Pr3+,
      Dy3+)/M-TiO2 had the persistent methyl orange (MO) photocatalytic degradation
      ability and the photocatalytic degradation went on reacting more than 90 min in
      dark after turning off the light. MgAl2O4:(Pr3+, Dy3+) emitted the light as a
      light source in dark which was absorbed by M-TiO2. The differences of
      MgAl2O4:(Pr3+, Dy3+)/Cr-TiO2, MgAl2O4:(Pr3+, Dy3+)/Ni-TiO2 and MgAl2O4:(Pr3+,
      Dy3+)/Co-TiO2 might be attributed to the difference in the metal ions doping. The
      composite MgAl2O4:(Pr3+, Dy3+)/Cr-TiO2 revealed the highest ability of persistent
      photocatalytic degradation methyl orange. Different metal ions doping made the
      TiO2 with different band gap.

PMID- 29448645
TI  - Fabrication of Pd-Pt/ZnO for High Sensitive Gaseous Formaldehyde Sensor.
AB  - In the present work, the successful fabrication of highly sensitive formaldehyde
      sensor based on ZnO doped Pd and Pt nanoparticles. The Pt-Pt/ZnO has been
      synthesized through a simple, facile and rapid method and characterized by
      several techniques. The fabricated Pt-Pt/ZnO exhibited a very high HCHO gas
      sensor response of 289.2 to 10 ppm, good selectivity and experimental detection
      limit of 0.5 ppm at room temperature. Response and recovery times for
      formaldehyde are 96 s and 46 s, respectively, at room temperature. Therefore, Pt
      Pt/ZnO is a promising application in the field of detection of formaldehyde.

PMID- 29448646
TI  - Nanoscale Characterization of Growth of Secondary Phases in Off-Stoichiometric
      CZTS Thin Films.
AB  - The presence of secondary phases is one of the main issues that hinder the growth
      of pure kesterite Cu2ZnSnS4 (CZTS) based thin films with suitable electronic and
      junction properties for efficient solar cell devices. In this work, CZTS thin
      films with varied Zn and Sn content have been prepared by RF-power controlled co
      sputtering deposition using Cu, ZnS and SnS targets and a subsequent
      sulphurization step. Detailed TEM investigations show that the film shows a
      layered structure with the majority of the top layer being the kesterite phase.
      Depending on the initial thin film composition, either about ~1 MUm Cu-rich and
      Zn-poor kesterite or stoichiometric CZTS is formed as top layer. X-ray
      diffraction, Raman spectroscopy and transmission electron microscopy reveal the
      presence of Cu2-xS, ZnS and SnO2 minor secondary phases in the form of
      nanoinclusions or nanoparticles or intermediate layers.

PMID- 29448647
TI  - Preparation and Visible-Light Driven Photocatalytic Properties of CuS/Reduced
      Graphene Oxide Composites.
AB  - The CuS/RGO composites were prepared using a facile one-step solvothermal method.
      The asobtained samples were characterized by X-ray diffraction (XRD), Raman
      spectra, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy
      (SEM), Brunner-Emmet-Teller (BET) measurements and UV-Vis spectrophotometry. The
      results showed that the CuS particles were uniformly dispersed on the surface of
      RGO and electronic migration effect existed between RGO and CuS. The
      photocatalytic activity of CuS/RGO composites was evaluated by the degradation of
      Cationic blue SD-BL, Cationic red X-5GN, Direct blue 86, Reactive blue KN-R,
      Methylene blue and Rhodamine B under visible light irradiation. The
      photocatalytic experiments showed that the CuS/RGO composites exhibited a better
      photocatalytic performance for organic dyes with absence of hydrogen peroxide
      (H2O2) due to the inhibition of recombination of electron-hole pair induced on
      the surface of CuS. The photodegradation ratio of Cationic blue SD-BL, Cationic
      red X-5GN, Direct blue 86, Reactive blue KN-R, Methylene blue and Rhodamine B
      increased to 100%, 95.8%, 99.5%, 87.8%, 100%, 81% after 75 min of irradiation,
      respectively. Moreover, no significant decline of CuS/RGO photocatalyst for
      photodegradation of dyes was observed after five cycles, indicating better
      photostability of the samples. Thus, the CuS/RGO composites could have a
      promising application in wastewater treatment.

PMID- 29448648
TI  - Redistribution of Welding Residual Stresses of Crack Tip Opening Displacement
      Specimen by Local Compression.
AB  - The demand of crack tip opening displacement (CTOD) test which evaluates fracture
      toughness of a cracked material is very important to ensure the stability of
      structure under severe service environment. The validity of the CTOD test result
      is judged using several criterions of the specification standards. One of them is
      the artificially generated fatigue pre-crack length inside the specimen. For
      acceptable CTOD test results, fatigue pre-crack must have a reasonable sharp
      crack front. The propagation of fatigue crack started from the tip of the
      machined notch, which might have propagated irregularly due to residual stress
      field. To overcome this problem, test codes suggest local compression method,
      reversed bending method and stepwise high-R ratio method to reduce the disparity
      of residual stress distribution inside the specimen. In this paper, the relation
      between the degree of local compression and distribution of welding residual
      stress has been analyzed by finite element analyses in order to determine the
      amount of effective local compression of the test piece. Analysis results show
      that initial welding residual stress is dramatically varied three-dimensionally
      while cutting, notch machining and local compressing due to the change of
      internal restraint force. From the simulation result, the authors find that there
      is an optimum amount of local compression to modify regularly for generating
      fatigue pre-crack propagation. In the case of 0.5% compressions of the model
      width is the most effective for uniforming residual stress distribution.

PMID- 29448649
TI  - A Self-Assembly Fluorescence Sensing Platform for Glutathione Detection Based on
      Eco-Friendly Quantum Dots and MnO2 Nanosheets.
AB  - Glutathione (GSH), a thiol-containing tripeptide, has a pivotal role in
      maintaining the normally physiological environment in biology. Here, we report a
      novel self-assembly fluorescence resonance energy transfer (FRET) sensing
      platform for GSH detection by using the environment-friendly Cu:Zn-In-S/ZnS
      quantum dots (QDs) and MnO2 nanosheets. In this assay, fluorescence of Cu:Zn- In
      S/ZnS QDs could be quenched by MnO2 nanosheets based on FRET. Upon the addition
      of GSH, MnO2 nanosheets were reduced into Mn2+ ions because of the rapid redox
      reaction, and consequently the fluorescence of QDs was recovered. A good linear
      relationship was obtained from 1 to 20 MUM for the detection of GSH with a low
      detection limit of 500 nM. Meanwhile, the sensing system also exhibited high
      selectivity against other electrolytes and biomolecules. Moreover, the
      satisfactory results in the determination of GSH in serum samples indicate that
      the assay holds great potential for detecting GSH in biological fluids. This
      method shows many advantages including high sensitivity, short assay time, good
      simplicity as well as label-free and environmental friendly, which is expected to
      facilitate the GSH quantification relating to biological and biomedical studies.

PMID- 29448650
TI  - Synthesis, Spectral and Photophysical Properties of Anthracene Substituted
      Phthalocyanines; A Study as Polyurethane Electrospun Nanofibers.
AB  - We have designed and synthesized novel symmetrical anthracene substituted
      zinc(II), copper(II), cobalt(II) and nickel(II) phthalocyanines (PC1, PC2, PC3
      and PC4) in this work. For this synthesis, we started from base-catalysed
      aromatic displacement reaction of 4-nitrophthalonitrile with 9-hydroxyanthracene.
      The resulting four phthalocyanines (PCs) have been fully characterized by a
      series of spectroscopic methods including electronic absorption, elemental
      analysis, MALDI-TOF mass, and IR spectroscopy. The aggregation behavior of these
      PCs was investigated in different concentrations of chloroform solution. Further
      thermal stability also investigated by TG analysis. Finally we successfully made
      phthalocyanine (PC1) blended polyurethane electrospun (ES) nanofibers.

PMID- 29448651
TI  - Studies on Conducting Polymer Blends: Synthesis and Characterizations of PVA/PVP
      Doped with CaCl2.
AB  - Calcium ion conducting polymer blend electrolyte films based on PVA/PVP complexed
      with CaCl2 have been prepared by solution casting technique. The structural
      changes of the polymer blends have been studied by X-ray diffraction (XRD) and
      Fourier transform infrared (FT-IR) spectroscopy. XRD and FT-IR studies confirmed
      the complex formation of polymer blends. Electrical conductivity was calculated
      with impedance analyzer within the frequency range 42 Hz-1 MHz and in the
      temperature range 303 K-340 K. The higher electrical conductivity value of 1.704
      * 10-4 Scm-1 was observed for 50PVA:50PVP:15 wt% CaCl2 concentration at room
      temperature. The magnitude of electrical conductivity was increased with the
      increase in the salt concentration as well as temperature. The electrical
      permittivity of the polymer films have been studied for various temperatures.

PMID- 29448652
TI  - Forced Convective Heat Transfer of Aqueous Al2O3 Nanofluid Through Shell and Tube
      Heat Exchanger.
AB  - This study presents the forced convective heat transfer of a nanofluid consisting
      of distilled water and different weight concentrations (1 wt% and 2 wt%) of Al2O3
      nanoparticles flowing in a vertical shell and tube heat exchanger under counter
      flow and laminar flow regime with certain constant heat flaxes (at 20  degrees C,
      30  degrees C, 40  degrees C and 50  degrees C). The Al2O3 nanoparticles of about
      50 nm diameter are used in the present study. Stability of aqueous Al2O3
      nanofluids, TEM, thermal conductivity, temperature differences, heat transfer
      rate, T-Q diagrams, LMTD and convective heat transfer coefficient are
      investigated experimentally. Experimental results emphasize the substantial
      enhancement of heat transfer due to the Al2O3 nanoparticles presence in the
      nanofluid. Heat transfer rate for distilled water and aqueous nanofluids are
      calculated after getting an efficient setup which shows 19.25% and 35.82%
      enhancement of heat transfer rate of 1 wt% and 2 wt% aqueous Al2O3 nanofluids as
      compared to that of distilled water. Finally, the analysis shows that though
      there are 27.33% and 59.08% enhancement of 1 wt% Al2O3 and 2 wt% Al2O3
      respectively as compared to that of distilled water at 30  degrees C, convective
      heat transfer coefficient decreases with increasing heat flux of heated fluid in
      this experimental setup.

PMID- 29448653
TI  - Self-Powered Sensors and Flexible Triboelectric Nanogenerator for Powering
      Portable Electronics.
AB  - We report on a flexible triboelectric nanogenerator (FTENG) designed using
      polydimethylsiloxane (PDMS) and aluminium (Al) combinations to convert ambient
      mechanical energy into electrical outputs. An open-circuit output voltage of ~40
      V and short-circuit current density of ~63.6 mA m-2 with power density 0.62 W m-2
      was easily obtained from the FTENG. The harvested mechanical energy is used for
      lighting ~100 light emitting diodes and to operate seven segment display enabling
      prospects for carbon-emission free environment friendly source for powering
      portable electronic devices. We have shown the capability of using the FTENG as
      self-powered weight and pressure sensors. Additionally, flexible design of the
      FTENG extends its application scope for self-powered tactile sensing in
      electronic skin for robotic application. The FTENG is simply designed, cost
      effective, scalable and high-throughput for possible uses in flexible
      electronics, self-powered systems and body sensor networks.

PMID- 29448654
TI  - Fabrication of ACF/GO/PEI Composite for Adsorption of Methyl Orange from Aqueous
      Solution.
AB  - ACF/GO/PEI (activated carbon fiber/graphene oxide/polyethyleneimine) composite
      was fabricated by crosslinking reaction and characterized with Scanning electron
      microscope (SEM), N2 physical adsorption and Fourier transform infrared
      spectroscopy (FTIR). Furthermore, the adsorption behavior of ACF/GO/PEI composite
      for methyl orange (MO) from aqueous solution was investigated. The experimental
      results showed that the specific surface area of ACF/GO/PEI composite is 1013.6
      m2/g and almost the same as that of original ACFs. However, with a larger
      fraction of mesopores, the pore structure of ACF/GO/PEI composite showed a
      significant change in comparison with that of original ACFs. Accordingly,
      ACF/GO/PEI composite indicated more excellent adsorptivity than ACFs. The tests
      also showed the adsorption capacity decreased with the increase in adsorbent mass
      and pH. The adsorption isotherm was fitted using both Langmuir and Freundlich
      adsorption models and the adsorption process was found to be well-described by
      Langmuir model. Moreover, the adsorption kinetics was discussed with pseudo-first
      order, pseudo-second-order and intra-particle diffusion models and the results
      disclosed the kinetic data were well fitted with pseudo-second-order kinetic
      model and the adsorption rate was controlled by intra-particle diffusion and film
      diffusion. Thermodynamic parameters including DeltaG, DeltaH and DeltaS showed
      that the adsorption process was a spontaneous, endothermic and increasing
      randomness process.

PMID- 29448655
TI  - A Facile Photoluminescent Probe for Picric Acid Detection Using Carbon Nanodots
      Prepared by Sichuan Bergamot.
AB  - A facile photoluminescent probe for picric acid (PA) detection was developed
      using photoluminescent carbon nanodots (C-dots), which was obtained from a
      traditional Chinese medicinal material Sichuan Bergamot via a one-step
      hydrothermal method for the first time. The as-prepared photoluminescent C-dots
      show favorable blue color photoluminescence with the maximum emission at 440 nm.
      It has been successfully applied as a photoluminescent probe for the detection of
      PA. This photoluminescent probe exhibits excellent sensitivity and selectivity
      toward PA from 0.4 MUM to 80 MUM with correlation coefficient (r) of 0.9987. The
      limit of detection (LOD) for PA is 82 nM. Furthermore, the proposed C-dots for
      photoluminescent probe detection of PA in real water samples (river water,
      refinery wastewater and pharmaceutical factory wastewater) by adding 5 MUM and 20
      MUM PA with satisfactory recoveries from 99.5% to 101.5%. These novel
      photoluminescent C-dots is promising in environmental analysis of PA.

PMID- 29448656
TI  - Tuneable Physicochemical Properties of Thermally Annealed Graphene Oxide Powder
      and Thin Films.
AB  - The tuneability of oxygen containing groups in graphene oxide (GO) that controls
      physicochemical properties is highly desirable for device applications. In this
      context, the thermally reduced graphene oxide (r-GO) powders and spin coated thin
      films with varying sp2/sp3 carbon network have been prepared using highly
      exfoliated GO (synthesized using modified Hummer's method with an innovative
      conjunction of lyophilisation). The additional step of lyophilisation results in
      the formation of highly exfoliated and monodispersed GO nanosheets as evidenced
      from FESEM, TEM, XRD, and Raman, FT-IR and UV-Vis spectroscopy. Spectroscopic
      analysis revealed the systematic evolution of r-GO with tuneable structural,
      optical and electrical properties as results of varying annealing temperatures
      (100-400  degrees C), due to restoration of sp2 conducting carbon network i.e.,
      the formation of new -C?C- network and Stones-Wales defect. The tuneability of
      physical properties is further corroborated by change in the resistance values,
      as evidenced through the current-voltage characteristics in GO thin film based
      lateral device structures with Ag and Al top contacts. Controlling
      physicochemical properties at relatively low processing temperature warrants the
      utilization of GO and r-GO in various electronic and optoelectronic devices.

PMID- 29448657
TI  - Numerical Analysis of the Temperature Impact on Performance of GaN-Based 460-nm
      Light-Emitting Diode.
AB  - The influence of temperature on the characteristics of a GaN-based 460-nm light
      emitting diode (LED) prepared on sapphire substrate was simulated using the
      SiLENSe and SpeCLED software programs. High temperatures impose negative effects
      on the performance of GaN-based LEDs. As the temperature increases, electrons
      acquire higher thermal energies, and therefore LEDs may suffer more from high
      current loss mechanisms, which in turn causes a reduction in the radiative
      recombination rate in the active region. The internal quantum efficiency was
      reduced by about 24% at a current density of 35 A/cm2, and the
      electroluminescence spectral peak wavelength was redshifted. The LED operated at
      260 K and exhibited its highest light output power of ~317.5 mW at a maximum
      injection current of 350 mA, compared to 212.2 mW for an LED operated at 400 K.
      However, increasing temperature does not cause a droop in efficiency under high
      injection conditions. The peak efficiency at 1 mA of injection current decreases
      more rapidly by ~15% with increasing temperature from 260 to 400 K than the
      efficiency at high injection current of 350 mA by ~11%.

PMID- 29448658
TI  - The Effect of Au/Ag Bimetallic Thin-Films on Surface Plasmon Resonance Properties
      Comparing with Those of Au and Ag Single Thin-Films.
AB  - The surface plasmon resonance (SPR) properties of Au/Ag bimetallic thin-film
      nanostructures were investigated to improve the chemical stability and the figure
      of merit (FOM) in the SPR sensors. The SPR characteristics such as resonance
      angle, extinction ratio, and full width half maximum (FWHM) were calculated by
      the simulation of the finite-difference time-domain method and were measured
      using the laser with a 632.8 nm wavelength in the Kretschmann-Raether
      configuration. The measured resonance angle, extinction ratio, FWHM of Au(20
      nm)/Ag(20 nm) thin-film nanostructure were found to be 44 degrees , 0.8, and 1.4
      degrees , respectively. The FOM values were determined to be 56.9 for Au/Ag
      bimetallic thin-film, 47.9 for Au(50 nm) single thin-film, and 89.1 for Ag(50 nm)
      single thin-film. Also the sensitivity values were about 53.5, 57.0, and 57.8
      degrees /RIU for Au(50 nm), Ag(50 nm), and Au(20 nm)/Ag(20 nm) thin-film
      nanostructures in the SPR sensors, respectively. The SPR properties of Au/Ag
      bimetallic thin-film nanostructures were compared with those of the Au and Ag
      single thin-film nanostructures.

PMID- 29448659
TI  - Development of a Spoke Type Torque Sensor Using Painting Carbon Nanotube Strain
      Sensors.
AB  - This study reports a hub-spoke type joint torque sensor involving strain gauges
      made of multiwalled carbon nanotubes (MWCNT). We developed the novel joint torque
      sensor for robots by means of MWCNT/epoxy strain sensors (0.8 wt%, gauge factor
      2) to overcome the limits of conventional foil strain gauges. Solution mixing
      process was hired to fabricate a liquid strain sensor that can easily be
      installed on any complicated surfaces. We painted the MWCNT/epoxy mixing liquid
      on the hub-spoke type joint torque sensor to form the piezoresistive strain
      gauges. The painted sensor converted its strain into torque by mean of the
      installed hub-spoke structure after signal processing. We acquired sufficient
      torque voltage responses from the painted MWCNT/epoxy strain sensor.

PMID- 29448660
TI  - Evaluation of Weldability for MAG and LASER with Galvannealed Steel.
AB  - Lower-arm, one of the components in automotive suspension module, has been
      fabricated by MAG welding in general which is lap jointed with 2 mm thick
      galvannealed steel sheet (SGAPH440). This welding process produces some problems
      such as significantly much spatters and weld defects of porosity in welded joint,
      which degrades productivity and weldability. Therefore, in order to solve these
      problems, this study has been tried to apply two types of solid wires with
      different chemical composition rate of Si and Mn, in MAG welding process.
      Moreover, the laser welding process has been adopted to fabricate the low-arm and
      compared with those of MAG welding, in terms of mechanical and metallurgical
      characteristics. It was observed that in MAG welded joints, much more spatters
      were occurred in using solid wire with higher Si and Mn contains. The maximum
      tensile-shear strength in laser welded joints was approximately 16.7 kN, which
      was almost equal to that of in MAG welded joints. The microstructure showed
      ferrite and martensite in weld metal in MAG and laser welded joints indicating no
      significantly grain size change.

PMID- 29448661
TI  - Study on Sand Erosion and Tribological Behavior of TiO2 Films Prepared on a Glass
      Surface.
AB  - TiO2 films with one, three or five layers were prepared on a glass surface using
      the sol-gel method. The crystal structure, the surface morphology and the
      thickness of the films were characterized by X-ray diffraction, atomic force
      microscopy and ellipsometry. The tribological properties of the TiO2 films were
      investigated by a tribometer. TiO2 thin films were eroded by sand-air injection.
      The erosion behavior and mechanism of TiO2 thin films in a sandstorm were
      analyzed by scanning electron microscopy. The results showed that the films were
      highly abraded with increased erosion speed and dose of sand. With an increase in
      film layers, the erosion resistance and wear resistance of the TiO2 films
      increased gradually. The erosion mechanism consists of the film being damaged
      mainly from the cutting action of micro-scratches from low angle erosion.
      Alternatively, for high angle erosion, the material is damaged mainly by squeeze
      deformation by the action of erosion. Because of the high strength and toughness
      of the TiO2 thin films, the wear of its coating from high angle erosion is more
      severe than that from low erosion angle.

PMID- 29448662
TI  - How Does Amino Acid Ligand Modulate Au Core Structure and Characteristics in
      Peptide Coated Au Nanocluster?
AB  - The atomic structures and the corresponding physicochemical properties of peptide
      coated Au nanoclusters determine their distinctive biological targeting
      applications. To learn the modulation of amino acid ligand on the atomic
      structure and electronic characteristics of coated Au core is the fundamental
      knowledge for peptide coated Au nanocluster design and construction. Based on our
      recent coated Au nanocluster configuration study (Nanoscale, 2016, 8, 11454), we
      built the typically simplified Au13(Cys-Au-Cys) system to more clearly learn the
      basic modulation information of amino acid ligand on Au core by the density
      functional theory (DFT) calculations. There are two isomers as ligand adjacent
      bonding (Iso1) and diagonal bonding (Iso2) to Au13 cores. The geometry
      optimizations indicate the adjacent bonding Iso1 is more stable than Iso2. More
      important, the Au13 core of Iso1 distorts much more significantly than that of
      Iso2 by Cys-Au-Cys bonding through the root-mean-square deviation (RMSD)
      analysis, which modulate their electronic characteristics in different ways. In
      addition, the frontier molecular orbital results of Au13(Cys-Au-Cys) isomers
      confirm that the Au cores mainly determine the blue shifts of Au13(Cys-Au-Cys)
      systems versus the original Au13 core in their UV-visible absorption spectrum
      studies. The configuration of Au13 core performs deformation under Cys-Au-Cys
      ligand modulation to reach new stability with distinct atomic structure and
      electronic properties, which could be the theory basis for peptide coated AuNCs
      design and construction.

PMID- 29448663
TI  - Enhanced Specific Capacitance of Few-Layer MoS2 Nanosheets via SDBS-Assisted
      Hydrothermal Method.
AB  - Few-layer MoS2 nanosheets have been successfully synthesized by a facile anionic
      surfactantassisted hydrothermal approach. The as-prepared samples are
      characterized by X-ray diffraction (XRD), Raman spectroscopy, scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). It is found that the
      anionic surfactant sodium dodecylbenzene sulfonate (SDBS) plays a crucial role in
      the formation of MoS2 nanosheets with few layers and rich exposed edges. The
      electrochemical performances of the as-prepared samples are evaluated by cyclic
      voltammogram, galvanostatic charge-discharge and electrochemical impedance
      spectroscopy. Compared with the pristine MoS2 without SDBS, the MoS2 nanosheets
      show a high specific capacitance of 223 F g-1 and its capacitance can still
      maintained a stable specific capacitance of 147 F g-1 after 500 cycles at 1 A g
      1. The enhancement in supercapacitors is attributed to few-layer structure and
      exposed active edges, which enables fast electron transportation between the
      electrode and electrolytes. Therefore, the MoS2 nanosheets will be a suitable
      candidate for electrochemical supercapacitor applications.

PMID- 29448664
TI  - Preparation of Partially Unzipped Carbon Nanotube/Ag (PUCNTs/Ag) Nanocomposite
      and Its Application for H2O2 Based Non-Enzymatic Sensor.
AB  - In the present work, the nanocomposite of the silver nanoparticles decorated
      partially unzipped carbon nanotubes (PUCNTs) (PUCNTs/Ag) was fabricated by in
      situ method, and its application as a sensitive non-enzymatic hydrogen peroxide
      (H2O2) sensor was then explored correspondingly. The measurements of transmission
      electron microscopy (TEM), fourier transform infrared (FTIR) spectroscopy and
      ultraviolet visible (UV-vis) absorption spectrum proved that the PUCNTs/Ag
      composite has been successfully prepared and the Ag nanoparticles dispersed on
      the surface of the PUCNTs and entered the inner of unzipped MWCNTs. Cyclic
      voltammetric (CV) measurement indicated that the PUCNTs/Ag nanocomposite showed
      the well-defined redox characteristics in 0.1 M phosphate buffer solution (PBS,
      pH = 7.5), and under the optimized experimental conditions, the current response
      of the as-obtained sensor towards electrochemical oxidation of H2O2 was linear
      with the concentration of H2O2 in the range of 0.0419 mM to 87 mM (R = 0.997) in
      the solution of 0.1 M PBS (pH = 7.5) at the applied potential of 0 V. The
      detection limit was 1 MUM with the sensitivity calculated as 1.115 * 103 MUA . M
      1 . cm-2 and the fast response achieved within 3 s. The constructed non-enzymatic
      sensor is one of the promising candidates due to it's good sensitivity,
      selectivity, and reproducibility.

PMID- 29448665
TI  - Pyrolysis Mechanism of Ionic Liquid Under Microwave Irradiation and the Formation
      of N-Doped Carbon.
AB  - The pyrolysis mechanism of the ionic liquid [BMIm]N(CN)2 under microwave
      irradiation was discussed for the first time. The trimerization of the anion
      N(CN)-2 and the formation of a framework were firstly caused by the microwave
      irradiation. And then the carbonization of the framework occurred when the
      temperature reached 330  degrees C. The pyrolysis product was graphitic
      nitrogendoped carbon and mainly originated from the anion N(CN)-2. The nitrogen
      content and graphitization degree of the nitrogen-doped carbon was relied on the
      pyrolysis temperature.

PMID- 29448666
TI  - Growth of Large-Area 2D MoS2 Arrays at Pre-Defined Locations Using Stencil Mask
      Lithography.
AB  - The growth of MoS2 layers of desired dimensions at predefined locations is
      essential for fabricating opto-electronic devices based solely on MoS2 or on
      hetero-structures based on MoS2. Here we present a new route for patterned growth
      of MoS2 by combining radio frequency (RF) magnetron sputtering, stencil mask
      lithography and vapour phase sulfurization. The present method does not involve
      chemical etchants and organic photoresist and hence provides a simplified process
      of achieving MoS2 patterns. Here, the control over the number of layers (mono,
      few and bulk) of MoS2 is achieved by varying the thickness of Mo films. The
      statistical variation in thickness i.e., number of MoS2 layers within the
      individual patterns is investigated from Raman mappings which revealed the
      uniform growth of 3-4 MoS2 layers. From Kelvin probe force microscopy, the
      surface potential values of MoS2 patterns lie in the range -350 to -370 mV, which
      is consistent with 2D MoS2 layer with thickness of 3-4 layers. The surface
      potential analysis across individual patterns indicates weakly n-type doping of
      few layers MoS2 with Fermi level located ~0.83-0.85 eV below the conduction band
      edge.

PMID- 29448667
TI  - Temperature Dependence of Oxide Semiconductor and Channel Effect of Thin Film
      Transistor.
AB  - ZTO was prepared on SiOC/ITO glass and the electrical characteristics were
      analyzed in accordance with the annealing temperature to research the temperature
      dependence and an amorphous structure. SiOC annealed at 150  degrees C as a gate
      insulator became an amorphous structure. The ZTO annealed at 150  degrees C had
      the capacitance without any variation. However, the capacitance of ZTO on SiOC
      annealed at 150  degrees C was increased due to the reduction of energy loss.
      ZTO/SiOC transistor was observed the ambipolar transfer characteristics with high
      stability and mobility in accordance with the decrement of drain voltages as a
      result of tunneling effect. Therefore it was obtained that the SiOC annealed at
      150  degrees C means the highest Schottky barrier (SB) at the interface of
      ZTO/SiOC as the optimization parameter.

PMID- 29448668
TI  - Effect of the Curved Fin Top Edge on the Electrical Characteristics of FinFETs.
AB  - The effect of the curved fin top edge on the electrical characteristics of
      FinFETs was investigated. The curvature radius of the fin top edge for the
      FinFETs was changed from 0 to 5 nm in order to determine the optimum condition of
      the electrical characteristics for the devices. The on-current level of the
      FinFETs with a curvature radius of 5 nm of fin top edge was 24.45% larger than
      that of the FinFETs with a cuboid fin. The electron current density and the
      electron mobility of the fin top edge for the FinFETs were larger than those for
      the FinFETs with a cuboid fin. The electrical characteristics of the FinFETs with
      a curvature radius of 5 nm for the fin top edge showed the best performance due
      to the largest expansion of the effective channel region.

PMID- 29448669
TI  - Interface State Density and Series Resistance of n-Type Nanocrystalline FeSi2/p
      Type Si Heterojunctions Formed by Utilizing Facing-Target Direct-Current
      Sputtering.
AB  - n-Type nanocrystalline FeSi2/p-type Si heterojunctions were formed by using
      facing-target direct- current sputtering at room temperature. The J-V
      characteristic results revealed that the reverse leakage current is large and the
      response under illumination of near-infrared light is very weak. The capacitance
      voltage-frequency (C-V-f) and conductance-voltage-frequency (G-V-f) measurements
      were carried out at room temperature in order to estimate the series resistance
      (Rs) by using the Nicollian-Brews method and the density of interface state (Nss)
      by using the Hill-Coleman method. By estimation according to the Nicollian-Brews
      method, the Rs value increases with decreasing f value. The Rs values at zero
      bias voltage were 2.07 Omega at 60 kHz and 1.54 Omega at 2 MHz, which are
      consistent with those calculated by using the Cheung's and Norde's methods. The
      obtained Rs should be attributable to the Rs existing in the ohmic contact and
      neutral regions, which is the current-limiting factor for junctions. The nss
      values calculated by using the Hill-Coleman method were 2.70 * 1014 eV-1cm-2 at
      60 kHz and 1.43 * 1013 eV-1cm-2 at 2 MHz. This result revealed the presence of
      interface states at the hetero-interface behaving as a leakage current center and
      a trap center of the photo-generated carrier, which degraded the junction
      properties at room temperature.

PMID- 29448670
TI  - Effects of Heat Treatment on Interfacial Behavior and Bonding Strength of Surface
      Activated Bonding Ti-Al Laminate.
AB  - The surface activated bonding (SAB) method generally has the advantage of high
      bonding strength, low contact resistance, and high microstructural stability at
      room temperature. In this study, Ti-Al laminates were produced by surface
      activated bonding with aluminum and titanium foils. Heat treatment was conducted
      at the temperature range from 200 to 550  degrees C in vacuum. The bonding
      strength Ti-Al laminates was measured by a peel test, and the interfacial
      characteristics were investigated microstructural observation. The results showed
      that the bonding strength was the highest with heat treatment at 400  degrees C,
      microstructure observation revealed that the bonding strength of the Ti-Al
      laminate was influenced by the interfacial characteristics.

PMID- 29448671
TI  - Evolution of Nanostructure Through Thickness of Deoxidized Low-Phosphorous Copper
      by Three-Layer Stack Accumulative Roll-Bonding.
AB  - A nanostructured deoxidized low-phosphorous copper (DLPC) was fabricated by three
      layer stack accumulative roll-bonding process. Three sheets of 1 mm in thickness,
      30 mm in width and 300 mm in length were stacked up and roll-bonded to thickness
      of 1 mm by two-pass cold rolling. The bonded sheet was cut in three pieces of
      same length, then stacked up and roll-bonded to the thickness of 1 mm again. The
      evolution of nanostructure through thickness with three-layer stack ARB were
      investigated in detail. It was found that the microstructure has been evolved
      from a dislocation cell structure to a nano grained structure with the proceeding
      of ARB cycles. The average grain thickness of 45 MUm in initial decreased to 170
      nm after 7 cycles of the ARB. The heterogeneity in microstructure through
      thickness was also largely decreased by the ARB. These results suggest that three
      layer stack ARB is an effective process for a formation of nanostructure of DLPC
      alloy.

PMID- 29448672
TI  - Investigating the Role of Substrate Tin Diffusion on Hematite Based
      Photoelectrochemical Water Splitting System.
AB  - Hematite (alpha-Fe2O3) nanostructures have been extensively studied as photo
      anodes for the conversion of sunlight into chemical fuels by water splitting. A
      number of factors limit the photo-activity of pristine hematite nanostructures,
      including poor electrical conductivity and long penetration depth of light.
      Previous studies have shown that use of tin (Sn) as an n-type dopant can
      substantially enhance the photoactivity of hematite photoanodes by modifying
      their morphological, optical and electrical properties. This article presents
      impedance spectroscopic investigation of interplay between Sn-doping and the
      photoanode performance for photoelectrochemical water splitting using hematite
      nanostructure. Mott-Schottky measurements show that the Sn dopant serves as
      electron donor and increases the donor density of Sn-doped alpha-Fe2O3
      nanostructured layer to 2.39 * 1019 cm-3. Photoelectrochemical impedance
      spectroscopy shows efficient photogenerated charge transfer from hematite to
      electrolyte in Sn-doped alpha-Fe2O3 nanostructure. The Sn-doped alpha-Fe2O3
      nanostructure exhibit a photocurrent density of 1.2 mA/cm2 at 1.4 V versus RHE
      electrode.

PMID- 29448673
TI  - A Phosphine-Free Route to Size-Adjustable CdSe and CdSe/CdS Core-Shell Quantum
      Dots for White-Light-Emitting Diodes.
AB  - The selenium dioxide was used as the precursor to synthesize wide-size-ranged
      CdSe quantum dots (2.4-5.7 nm) via hot-injection route. The CdSe quantum dots are
      featured with high crystalline, monodisperse, zinc blende structure and wide
      emission region (530-635 nm). In order to improve the stability and quantum
      yield, a phosphine-free single-molecular precursor approach is used to obtain
      CdSe/CdS core/shell quantum dots. The CdSe/CdS quantum dots are highly
      fluorescent with quantum yield up to 65%, and persist the good monodispersity and
      high crystallinity. Moreover, the quantum dots white light-emitting-diodes are
      fabricated by using the resultant red emission core/shell quantum dots and
      Y3Al5O12:Ce3+ yellow phosphors as color-conversion layers on a blue InGaN chip.
      The prepared light-emitting-diodes show good performance with CIE-1931
      coordinated of (0.3583, 0.3349), an Ra of 92.9, and a Tc of 4410 K at 20 mA,
      which indicate that the combination of red-emission QDs and yellow phophors as a
      promising approach to obtain warm WLEDs with good color rendering.

PMID- 29448674
TI  - Preparation and Performance of Porous Polymer Electrolytes Doped with Nano-Al2O3.
AB  - Porous polymer electrolytes (PPEs) doped with nano-Al2O3 were prepared by a joint
      application of ultrasonic treatment and control evaporation in vacuum oven. The
      morphology, pore size distribution, thermal, electrochemical and mechanical
      properties of the PPEs were investigated. The porosity distribution of PPEs was
      uniform and their pore size was relatively modest. The total resistance (Rt) of
      PPEs with 10% Al2O3 is only 9 Omega at 80  degrees C. The maximum tensile
      strength of the PPEs membranes reached to 24.43 MPa. The results show that nano
      Al2O3 can improve the comprehensive performance of PPEs without compromising
      their conductivity and diplayed the good application prospects of Al2O3-modified
      PPEs for lithium-ion batteries.

PMID- 29448675
TI  - Broadband UV Excited LaF3:Eu3+ Based Inorganic-Organic Mixed Hybrid Nanoparticles
      for Strong Luminescence.
AB  - Lanthanide ion doped nanoparticles can coordinate with some organic ligands to
      form the inorganic-organic hybrid nanoparticles, which exhibit greatly enhanced
      luminescence as a result of the energy transfer from the organic ligands to the
      lanthanide ions. However, when coordinating with a single type of organic ligand,
      their luminescence excitation spectral bandwidth is still quite limited. In this
      work, Eu3+-doped LaF3 (LaF3:Eu3+) nanoparticles, as the model inorganic material,
      were synthesized using the hydrothermal method. Instead of coordinating with a
      single type of organic ligand as previously studied, the LaF3:Eu3+ nanoparticles
      simultaneously coordinate with both benzoic acid and 2-thenoyltrifluoroacetone to
      form the inorganic-organic mixed hybrid nanoparticles. The mixed hybrid
      nanoparticles possess a broadband excitation spectrum (200~400 nm) which
      perfectly covers the entire ultraviolet (UV) spectral range of the solar
      radiation. By down-converting the UV light to visible light, their broadband UV
      excitation spectrum will be extremely beneficial to the enhancement of the
      conversion efficiency of silicon solar cells.

PMID- 29448676
TI  - A Sensor Based on LiCl/NaA Zeolite Composites for Effective Humidity Sensing.
AB  - LiCl/NaA zeolite composites were successfully prepared by doping 1 wt%, 2 wt%, 5
      wt%, and 8 wt% of LiCl into NaA zeolite. The humidity sensing properties of
      LiCl/NaA composites were investigated among 11% 95% relative humidity (RH). The
      LiCl/NaA composites exhibited better humidity sensing properties than pure NaA
      zeolite. The sensor made by 2 wt% Li-doped NaA zeolite possesses the best
      linearly in the whole RH. These results demonstrate that the LiCl/NaA composites
      have the potential application in humidity sensing.

PMID- 29448677
TI  - Microstructure and Electrochemical Performance of Co3O4 Nanopillars Calcinated at
      Various Temperatures.
AB  - One-dimensional (1D) Co3O4 nanopillars were prepared by a facile hydrothermal
      calcination method, which involved low thermal decomposition of Co(OH)y(CO3)0.5(2
      y) . 11H2O at different temperatures. Microstructure, lithium-storage performance
      and the conductivity of the Co3O4 nanopillars calcined at different temperatures
      were systematically investigated. It was revealed that the calcined temperature
      has an effect on the particle size, crystallinity, and morphology of the Co3O4
      nanopillars, which further influenced its electrochemical performance. It was
      found that when the calcined temperature and time were 450  degrees C and 2 h,
      respectively, the obtained Co3O4 nanopillars with the length of 60-100 nm and
      width of 30-40 nm, presented good lithium-storage performance with a high
      reversible capacity of 805.8 mAh g-1 after 30 cycles at a current density of 100
      mA g-1. In addition, the Co3O4 nanopillars electrode possessed the smallest
      semicircle diameter, which implied that Co3O4 nanopillars presented the lowest
      contact and charge-transfer impedances, originating from its good crystallinity
      and 1D nanocolumnar structure.

PMID- 29448678
TI  - Fabrication and Friction Coefficient of Graphene Oxide Reinforced Hydroxyapatite
      Composite.
AB  - Graphene oxide (GO) reinforced hydroxyapatite (HA) composites with various
      contents of GO (HA/GO-C) were synthesized with addition of cetyltrimethyl
      ammonium bromide (CTAB) by a wetchemical precipitation method using diammonium
      hydrogen phosphate ((NH4)2HPO4) and calcium nitrate (Ca(NO3)2 . 4H2O) as the
      initial reactants, and their structure, morphology, crystallization, specific
      surface area were studied by FT-IR, SEM, Raman spectroscopy, XRD and BET.
      Particularly, the influence of GO addition and appiled load on the friction
      coefficient of the obtained composites was investigated. Also, the influence of
      GO addition on microhardness of the composite was evaluated. The results
      suggested that HA successfully grafted over GO nanosheets whose structure was
      preserved. The layer spacing of HA/GO-C composite was enlarged by addition of
      CTAB in synthesis process. The friction coefficient of the composite gradually
      decreased with increase of GO content in composite and increased with increase in
      applied load. The microhardness of the composites increased with increase of GO
      content. The obtained HA/GO-C composites may have a potential application in
      biomedical engineering.

PMID- 29448679
TI  - The Effect of Precursor Composition on the Structural Properties of
      Nanocrystalline Diamond Films.
AB  - Nanocrystalline diamond (NCD) films were grown by hot filament CVD and the
      precursor composition dependence of the structural properties was examined. Films
      grown at 1 and 2 CH4 Vol% were found to be NCD layers with grain sizes of ~23-25
      nm while films grown at 3-5 Vol% were identified as the mixtures of
      microcrystalline diamond and graphitic phase. The sp2/sp3 bonded carbon ratio in
      the grown films increased as the CH4 content increased up to 3 Vol% and then
      decreased beyond 4 Vol%. Microstructure and deposition rate were also found to be
      affected by the precursor composition and the NCD film grown at 1 CH4 Vol% showed
      a very dense microstructure and the highest deposition rate of ~3 nm/min.

PMID- 29448680
TI  - Near-Infrared to Visible Up-Conversion Luminescence Characteristics of Er, Yb Co
      Doped LaVO4 Phosphors.
AB  - Er3+ and Yb3+ co-doped LaVO4 phosphors were synthesized by the facile solid state
      reaction method. Er3+ ions concentrations were changed from 0.01 to 0.2 mol for
      the fixed Yb3+ ions concentration at 0.15 mol. The crystalline structures of the
      phosphors were investigated by X-ray diffraction (XRD). The composition of the
      phosphors were investigated by X-ray photoelectron spectroscopy (XPS) analysis.
      The photoluminescence emissions based on the blue emission near 466 nm and green
      emission near 553 nm were observed and the highest emission intensity occurred
      for the sample LaVO4:Yb0.15, Er0.20. The green and red up-conversion emissions
      were observed in Er3+, Yb3+ co-doped LaVO4 phosphors under the excitation of 980
      nm laser diode. LaVO3:Yb3+, Er3+ phosphors could be utilized to produce green
      colored LEDs by excitation for infra-red LED.

PMID- 29448681
TI  - Improved Heat Dissipation of High-Power LED Lighting by a Lens Plate with
      Thermally-Conductive Plastics.
AB  - The junction temperature of high-power LED lighting was reduced effectively using
      a lens plate made from a thermally-conductive plastics (TCP). TCP has an
      excellent thermal conductivity, approximately 5 times that of
      polymethylmethacrylate (PMMA). Two sets of high-power LED lighting were designed
      using a multi array LED package with a lens plate for thermal simulation. The
      difference between two models was the materials of the lens plate. The lens
      plates of first and second models were fabricated by PMMA (PMMA lighting) and TCP
      (TCP lighting), respectively. At the lens plate, the simulated temperature of the
      TCP lighting was higher than that of the PMMA lighting. Near the LED package, the
      temperature of the TCP lighting was 2  degrees C lower than that of the PMMA
      lighting. This was well matched with the measured temperature of the fabricated
      lighting with TCP and PMMA.

PMID- 29448683
TI  - Using KrF ELA to Improve Gate-Stacked LaAlO3/ZrO2 Indium Gallium Zinc Oxide Thin
      Film Transistors with Novel Atmospheric Pressure Plasma-Enhanced Chemical Vapor
      Deposition Technique.
AB  - Atmospheric pressure plasma-enhanced chemical vapor deposition (AP-PECVD)
      technique and KrF excimer laser annealing (ELA) were employed for the fabrication
      of indium gallium zinc oxide thin-film transistors (IGZO-TFTs). Device with a 150
      mJ/cm2 laser annealing densities demonstrated excellent electrical
      characteristics with improved on/off current ratio of 4.7*107, high channel
      mobility of 10 cm2/V-s, and low subthreshold swing of 0.15 V/dec. The
      improvements are attributed to the adjustment of oxygen vacancies in the IGZO
      channel to an appropriate range of around 28.3% and the reduction of traps at the
      high-k/IGZO interface.

PMID- 29448682
TI  - Optical Characteristics of Double Layered Plasmonic Structure Using
      Nanopatterning Process.
AB  - A double layered plasmonic device based on transferring technique with
      polystyrene nano-beads is analyzed and demonstrated to increase the sensing
      characteristics of plasmonic sensor system. The double layered plasmonic devices
      are calculated using the three-dimensional finite-difference time-domain method
      for the width and thickness of the nano-hole structures. The double layered
      plasmonic devices with different diameters of the Au nano-hole are fabricated by
      transferring method with commercially available chloromethyl latex with a
      diameter of 0.42 MUm. The optimum sensing characteristic of the proposed
      plasmonic device is obtained with the film and the hole thickness of 15 and 15 nm
      in the 246 nm wide nano-hole size. The best sensitivity of the proposed plasmonic
      sensor is 67.7 degree/RIU when the sensitivity of the conventional plasmonic
      sensor is 42.2 degree/RIU.

PMID- 29448684
TI  - High Temperature Corrosion of TiAlCrSiN Films in N2/0.1%H2S Gas.
AB  - Nanomultilayered TiAlCrSiN film was corroded in N2/0.1%H2S-mixed gas at 900 
      degrees C for 5-300 h. It corroded to TiO2, alpha-Al2O3, and Cr2O3. From the
      early corrosion stage, not only the outward diffusion of Al, Ti, Cr, and Si but
      also the inward migration of oxygen occurred. As the corrosion proceeded, the
      outermost TiO2 layer, outer (Ti-depleted, (Al,Cr)-rich)-oxide layer, inner (Ti
      rich, (Al,Cr)-depleted)-oxide layer, and partially oxidizing innermost film
      formed on the oxygenaffected film.

PMID- 29448685
TI  - Fabrication of Si Micro Mold via Tribo-Nanolithography Using Micro
      Polycrystalline Diamond Cantilever Tool.
AB  - A direct mechanical nanomachining, tribo-nanolithography (TNL), has been
      developed to fabricate micro mold on Si substrate in mechanical milling mode. An
      atomic force microscope (AFM) tip is replaced by a lab-made Si cantilever with a
      polycrystalline diamond (PCD) tool. Mechanical cutting by PCD tool enables simple
      fabrication of micro molds with several tens of nanometers depth. Machined
      cavities of the Si substrate are prepared as a master mold for additional micro
      molding using polydimethylsiloxane (PDMS). Micro cavities are successfully
      duplicated in positive patterns similar to soft lithography. Normal loads of
      cantilever and AFM topographical images are used to discuss micro mold and micro
      molding characteristics.

PMID- 29448686
TI  - Effect of the Spray Distance on the Properties of High Velocity Oxygen-Fuel
      (HVOF) Sprayed WC-12Co Coatings.
AB  - In this study influence of spray distance on the properties of WC-12Co coatings
      deposited by HVOF was investigated. WC-12Co coating was sprayed at spray distance
      of 300, 385 and 450 mm. From microstructure observation, it is confirmed that the
      porosity of coatings increases with increasing the spray distance. The X-ray
      diffraction patterns indicate that the coatings consist of pure WC, W, and Co as
      well as W2C and Co6W6C phases. The increase of the spray distance accelerated the
      decarburization of coatings. From micro hardness tests, it was found that the
      hardness and the fracture toughness decreased with increasing spray distance.
      These mechanical properties would be related with not only porosity but also the
      degree of decarburization.

PMID- 29448687
TI  - The Effect of Tool Profiles on Mechanical Properties of Friction Stir Welded
      Al5052 T-Joints.
AB  - Al5052 T butt joints with two skins (5 mm) and one stringer (3 mm) has been
      successfully welded by friction stir welding (FSW). Notably, this paper has been
      investigated the effect of tool shape on welded formation mechanism and
      mechanical properties. The used shapes of tool pin are two types which are
      cylinder (type 1) and frustum (type 2). Dimension on two types of tool pin shape
      is respectively pin length of 4.7 mm and pin diameter of frustum type of top (5
      mm) and bottom (3 mm). The results of experiment show that inner defects in FSWed
      T-joints increase significantly in accordance with traverse speed. The maximum
      tensile strength of welded joint fabricated using type 1 is equivalent to 85%
      that of the base metal, which is approximately 10% higher than that of type 2.
      Because welded joint of type 1 has more smoothly plastic flow in comparison with
      type 2. Consequently, the results show that type 1 is better appropriate for
      friction stir welded Al5052 T butt joints than type 2.

PMID- 29448688
TI  - Effect of Self-Heating on the Electrical Characteristics of Strained Si FinFETs.
AB  - Self-heating effect (SHE) on the electrical characteristics of fin field-effect
      transistors (FinFETs) model with a strained Si channel was investigated by using
      a three-dimensional simulation tool. Strain was applied from 0.1 to 2.0 GPa by
      changing Si mole fraction of the Si1-xGex. Simulation results showed that the
      drain current of the strained Si FinFETs increased with increasing applied strain
      from 0.5 to 2.0 GPa. The drain current of the FinFETs under strain of 2.0 GPa
      increased up to 20.59 MUA. While the drain current of the FinFETs without a SHE
      increased with increasing strain, the increase of the drain current generating
      from the strain interrupted the applications for the practical device operation
      due to a large SHE. The drain current decreased due to the increased scattering
      resulting from the increased device temperature with an increase in the SHE.

PMID- 29448689
TI  - Effects of the Grain Boundary and Interface Traps on the Electrical
      Characteristics of 3D NAND Flash Memory Devices.
AB  - Three-dimensional (3D) NAND flash memory devices having a poly-silicon channel
      with grain boundaries, the cylindrical macaroni channel being outside the inter
      oxide filler layer and inside the tunneling oxide layer, were evaluated. The
      effects of the grain size, grain boundary trap density, and interface trap
      density at the interfaces between the channel and the oxide layers on the
      electrical characteristics of 3D NAND flash memory devices were investigated. The
      electron density of the channel was changed depending on the grain boundary trap
      density and the position of the grain boundary trap in the channel. The grain
      boundary traps increased the potential barrier and decreased the electron density
      of the channel. The threshold voltage increased with increasing grain boundary
      trap density and interface trap density.

PMID- 29448690
TI  - Characteristics of Nano Grained AA1050/AA5052 Al Sheets Fabricated by
      Accumulative Roll-Bonding.
AB  - Accumulative roll-bonding (ARB) is the most appropriate process for sheet-shaped
      materials because it can be carried out readily by utilizing the conventional
      rolling apparatus. In this study, a nanostructured AA1050/AA5052 Al alloy sheet
      was successfully fabricated by four-layer stack ARB process. The ARB of AA1050
      and AA5052 alloy sheets was performed up to 6 cycles without a lubricant at
      ambient temperature. The sample fabricated by the ARB was a multi-layer aluminum
      alloy sheet in which AA1050 and AA5052 layers are alternately stacked. The layer
      thickness of the each alloy became thinner and elongated to the rolling direction
      with the number of ARB cycles. The grain size decreased with increasing of the
      number of ARB cycles, after 6 cycles it became about 180 nm in thickness. The
      fraction of high angle grain boundaries increased with the number of ARB cycles.
      The tensile strength also increased with the ARB, it reached 305 MPa which is
      about 2.1 times that of the as-received AA1050. The mechanical properties of a
      multi-layer AA1050/AA5052 alloy fabricated by the ARB were compared to those of
      the other materials.

PMID- 29448691
TI  - Grain Refinement of Al-Si-Fe-Cu-Zn-Mn Based Alloy by Al-Ti-B Alloy and Its Effect
      on Mechanical Properties.
AB  - We investigated the effects of Al-5.0wt%Ti-1.0wt%B addition on the microstructure
      and mechanical properties of the as-extruded Al-0.15wt%Si-0.2wt%Fe-0.3wt%Cu
      0.15wt%Zn-0.9wt%Mn based alloys. The Aluminum alloy melt was held at 800  degrees
      C and then poured into a mould at 200  degrees C. Aluminum alloys were hot
      extruded into a rod that was 12 mm in thickness with a reduction ratio of 38:1.
      AlTiB addition to Al-0.15Si-0.2Fe-0.3Cu-0.15Zn-0.9Mn based alloys resulted in the
      formation of Al3Ti and TiB2 intermetallic compounds and grain refinement. With
      increasing of addition AlTiB, ultimate tensile strength increased from 93.38 to
      99.02 to 100.01 MPa. The tensile strength of the as-extruded alloys was improved
      due to the formation of intermetallic compounds and grain refinement.

PMID- 29448692
TI  - Preparation of CaCO3 and CaO Nanoparticles via Solid-State Conversion of Calcium
      Oleate Precursor.
AB  - Calcium carbonate (CaCO3) and monodisperse calcium oxide nanoparticles (CaO NPs)
      are prepared by the calcination of solid-state calcium oleate precursor in air
      condition. The effect of calcination temperature on the synthesis of CaCO3 and
      CaO NPs is examined. The polymorphism is confirmed by X-ray diffraction
      spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), and
      thermogravimetric analysis (TGA). The sample morphologies including their size
      and size distribution are investigated by field emission scanning electron
      microscopy (FESEM). Calcination of calcium oleate between 400 and 550  degrees C
      results in CaCO3 NPs with mean sizes from 82 to 98 nm, whereas monodisperse
      spherical CaO NPs are obtained at 650  degrees C and an average size is estimated
      to be 40 nm. Beyond 650  degrees C, the size of CaO NPs increases with broad size
      distribution. The results of this study provide a novel approach to monodisperse
      CaCO3 and CaO NPs that can be applied in a variety of fundamental and industrial
      fields.

PMID- 29448693
TI  - 3D MnCo2O4.5 Nanorod Arrays on Ni Foam as Binder-Free Anodes for Li-Ion
      Batteries.
AB  - It is a key to develop novel electrode materials with high energy and power
      density for advanced batteries to meet the demand of electric vehicles (EVs).
      Manganese cobalt oxides which can react with a large number of ions from the
      electrolyte for electrochemical energy storage are developing into the promising
      electrode materials. In this work, well-ordered MnCo2O4.5 nanorod arrays (MCO
      NRAs) are prepared on Ni foam by a general route of hydrothermal growth and low
      temperature annealing treatment. The samples deliver a high initial capacity of
      1402.6 mAh g-1 at the current density of 100 mA g-1 and rate capacity of 528 mAh
      g-1 when the current density is improved 10 times as binder-free anodes for Li
      ion batteries (LIBs). After 60 cycles at the current density of 200 mA g-1, the
      MnCo2O4.5 nanorods still achieve 603 mAh g-1 with capacity retention of 66%
      (compared with the second discharge capacity). The superior electrochemical
      properties are due to the fascinating architecture which increases the reaction
      area and structural stability, reduces ion and electron transport distance and
      provides good strain release. Hence, MnCo2O4.5 nanorod arrays are promised as
      advanced anodes for future LIBs with completely meeting the demand of EVs.

PMID- 29448694
TI  - Two Methods for Intercalation of Surfactants into Graphite Oxide.
AB  - The intercalation properties of graphite oxide are important; however, the
      specific processes and mechanisms associated with intercalation have rarely been
      elucidated. In this paper, two types of surfactants, polyvinylpyrrolidone and
      tetradecyltrimethylammonium bromide, were used to thoroughly explore the
      intercalation properties of graphite oxide. The polyvinylpyrrolidone and
      tetradecyltrimethylammonium bromide-intercalated graphite oxide composites were
      synthesized under different conditions and characterized by X-ray diffraction,
      Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray
      energy dispersive spectroscopy, and transmission electron microscopy. It was
      found that polyvinylpyrrolidone could be directly intercalated into the graphite
      oxide layers and tetradecyltrimethylammonium bromide could not effectively react
      with the waterdispersed graphite oxide. With a low quantity of
      polyvinylpyrrolidone, only a part of the graphite oxide was intercalated, and the
      interlayer spacing of the polyvinylpyrrolidone-intercalated composites increased
      as the polyvinylpyrrolidone: graphite oxide mass ratio increased. When the
      graphite oxide was dispersed in a 0.05 N NaOH solution, the
      tetradecyltrimethylammonium bromide rapidly reacted with the graphite oxide,
      while the mixture of polyvinylpyrrolidone and graphite oxide could not be
      effectively separated. The intercalated spacing of the
      tetradecyltrimethylammonium bromideintercalated graphite oxide increased with the
      tetradecyltrimethylammonium bromide: graphite oxide mass ratio, but its
      crystalline structure was not as ordered as the polyvinylpyrrolidone-intercalated
      graphite oxide prepared in the water solution. The infrared spectra of the two
      surfactant-intercalated graphite oxide samples revealed that the
      polyvinylpyrrolidone is bonded to the graphite oxide via hydrogen bonding, while
      the tetradecyltrimethylammonium bromide is bonded via ionic bonding. The
      mechanism analysis indicated that the polyvinylpyrrolidone could directly enter
      the graphite oxide layers in the water solution because of the driving force of
      hydrogen bonding. However, processes such as graphite oxide exfoliation,
      reactions between the graphite oxide and tetradecyltrimethylammonium bromide, and
      reaggregation of the graphite oxide sheets are necessary for the formation of
      tetradecyltrimethylammonium bromide-intercalated graphite oxide.

PMID- 29448695
TI  - Study on Surface and Crystallinity of TiO2 Microspheres as the Photoanode of Dye
      Sensitized Solar Cells.
AB  - In this study, Titanium dioxide (TiO2) microspheres were synthesized by a
      hydrothermal method from the same precursor: titanium sulfate. Two different TiO2
      microspheres with different surface and crystallinity were fabricated by adding
      different additives as the photoanode of dye-sensitized solar cells (DSSCs). The
      growth mechanisms of the TiO2 microspheres were discussed. The effect of surface
      status and the crystallinity of the TiO2 microspheres on the photovoltaic
      characteristic of DSSCs were investigated. It was found that when the TiO2
      microsphere with loose construction and rough surfaces along with better
      crystallinity was applied on photoanode, the DSSC exhibited better photoelectric
      performance than the DSSC with dense TiO2 microsphere photoanode. TiO2
      microsphere with loose construction and rough surface applied to photoanode, the
      DSSC showed photoelectric conversion performance of 3.83% which is 53.8% higher
      than DSSC with dense and smooth TiO2 microsphere photoanode, and it is also
      superior to the DSSC with P25 photoanode.

PMID- 29448696
TI  - Fabrication of TiO2 Nanostructures on Ti3SiC2 Substrate by Anodic Oxidation.
AB  - A TiO2 nanostructure was prepared on a Ti3SiC2 substrate with different water and
      NH4F concentrations in a fluoride-containing ethylene glycol electrolyte via an
      anodization process using the same constant-anodization potentials, anodization
      duration and temperature. The as-prepared samples were characterized by a field
      emission scanning electron microscope equipped with an energy dispersive X-ray
      spectroscope, as well as by X-ray diffraction and X-ray photoelectron
      spectroscopy. The influence of the anodizing parameters and annealing temperature
      on the morphology of the nanostructure and the phase structure was studied. The
      results showed that the scattered TiO2 nanotubes and TiO2 nanoporous films were
      successfully fabricated in the glycol electrolyte containing (3.0 wt%) NH4F +(5.0
      vol%) H2O. The as-prepared samples before calcination were amorphous and could
      transform to the anatase phase at temperatures higher than 500  degrees C. As the
      annealing temperature increased, the crystallization of the anatase phase was
      enhanced, and the rutile phase appeared at 600  degrees C. The as-prepared
      samples mainly consisted of oxides. Ti2O3 and SiO2 oxides were present in
      addition to TiO2.

PMID- 29448697
TI  - Characterization of DDAB/Cholesterol Vesicles and Its Comparison with
      Lipid/Cholesterol Vesicles.
AB  - Vesicles prepared by synthetic surfactant, DDAB (dilauryldimethylammonium
      bromide), were modified with cholesterol and their membrane surface properties of
      the vesicle were characterized through the analyses of fluorescent probes, such
      as Laurdan (6-lauroyl-2-dimethylaminonaphthalene) and DPH (1,6-diphenyl-1,3,5
      hexatriene). The self-assembly of DDAB with cholesterol showed stable vesicle
      structure with a mean diameter of 127 nm through the dynamic light scattering
      analysis. While the DDAB vesicle showed high polarity and high fluidity, the
      modification of the DDAB vesicle with cholesterol lead to the formation of
      "heterogeneous phase" on the vesicle membrane. DDAB:cholesterol = 70:30 vesicle
      showed unique characteristics that represents polar environment but lower
      fluidity. A novel platform for the chemical process in aqueous media can be
      expected by using the artificial surfactant vesicles modified with cholesterol.

PMID- 29448698
TI  - Rapid Macroscopic-Scale Assembly of Ag Nanowires at the Water/Air Interface.
AB  - Rapid macroscopic-scale assembly of Ag nanowires was demonstrated through facile
      self-assembly at the water/air interface. This self-assembly was induced by
      heating due to the surface tension effect and convection. Interestingly, a
      rippled hairstyle superstructure was observed when the aqueous dispersions of
      thinner Ag nanowires were heated. Applying the Euler buckling theory for a set of
      aligned Ag nanowires, it was found that the water surface tension was sufficient
      to bend or buckle these free Ag nanowires trapped between two nanowire stripes,
      which resulted in the formation of the rippled hairstyle superstructure. However,
      the formation of the nanowire stripes was driven by steric repulsion of nanowires
      along with their short-range van der Waals interactions and later lateral
      capillary attraction between large building blocks. Such control over self
      assembly is key for designing hierarchically ordered structures, which opens a
      new opportunity in the exploration of novel properties and the development of new
      applications.

PMID- 29448699
TI  - Synthesis of Nanoscale Fully Stabilized Zirconia Powders by Urea Hydrolysis,
      Sintering and Electrical Characterization.
AB  - Active nanoscale powders of cubic phase zirconia stabilized with yttria,
      gadolinia, and scandia were successfully prepared by urea hydrolysis. Synthetic
      cubic zirconia powders had homogeneous, nanoscale, and less-agglomeration
      characteristics. Dense pellets of grain size about 0.4 MUm exhibited grain
      boundary blocking resistance compared to the high frequency bulk resistance.
      Gadolinium doped system exhibited highest ionic resistivity. Yttria stabilized
      zirconia by urea hydrolysis in this work showed smaller ionic resistivity than
      the sample prepared from the commercial powder.

PMID- 29448700
TI  - UV Photoluminescence of Alumino-Germano-Silicate Glass Optical Fiber Incorporated
      with Gd2O3 Nano-Particles Upon Illumination of Xenon-Lamp.
AB  - Alumino-germano-silicate glass optical fiber incorporated with Gd2O3 nano
      particles (NPs) was developed by using the modified chemical vapor deposition and
      the drawing process. The formation of spherical Gd2O3 NPs in the fiber core with
      average diameter of 10.8 nm was confirmed by the TEM. The distinct absorption
      peaks in the fiber preform appearing in the UV region at 205, 247, 253, 274, and
      312 nm were due to the incorporated Gd2O3 NPs via reorganization of the seven 4f
      electrons into various multiplets of Gd ions. In the case of the optical fiber
      obtained by drawing of the preform at high temperature about 2150  degrees C,
      absorption peaks due to Gd2O3 NPs were found to appear at 383 and 455 nm, which
      were red-shifted from 274 and 312 nm of the preform, respectively, and it may be
      due to increase in the size of Gd2O3 NPs after the drawing process. To
      investigate the photoluminescence (PL) property for UV sensor applications, the
      PL of the fiber was obtained by illumination of the Xenon-lamp. A PL band
      appeared in the wavelength band from 370 nm to 450 nm, centering at about 400 nm,
      which can be attributed to the presence of Gd2O3 NPs embedded in the fiber core.
      It was also found that the PL intensity at 400 nm showed linear dependence with
      the excitation power from 0 to 400 W.

PMID- 29448701
TI  - Up-Conversion Luminescence Properties of LaGaO3:Yb3+, Er3+ Phosphors.
AB  - LaGaO3:Er3+, Yb3+ powder with different Er3+ contents (0.01~0.10 mol) was
      synthesized by a conventional solid-state reaction. The structure, morphology and
      photoluminescence properties of the as-prepared phosphors were characterized by X
      ray diffraction (XRD), scanning electron microscopy (SEM), and fluorescence
      spectrophotometer techniques, respectively. The photoluminescence (PL) emissions
      based on the green emission near 522 and 544 nm were observed and the highest
      emission intensity occurred for the sample LaGaO3:Yb0.15, Er0.07. The green and
      red up-conversion emissions were observed in Er3+, Yb3+ co-doped LaGaO3 phosphors
      under the excitation of 980 nm laser diode.

PMID- 29448702
TI  - Study on Strain Compensation for Multiple-Quantum Well in Infrared Light-Emitting
      Diode Using the InxGa1-xP Strain Barrier.
AB  - Strain compensation for multiple-quantum wells (MQWs) relative to the efficiency
      improvement of infrared light-emitting diodes (IR-LEDs) was investigated through
      the use of an InxGa1-xP strain barrier. The InxGa1-xP barrier, which was inserted
      between the n-confinement and active regions, developed for the reduction of
      lattice-mismatched strains in GaAs/AlGaAs and InGaAs/GaAs MQWs. Through
      photoluminescence, improved intensity was displayed in InGaAs/GaAs MQWs having
      InxGa1-xP strain barriers, with a significant increase in the intensity observed
      at the In0.47GaP strain barrier. This result is attributed to strain compensation
      between the In0.47GaP tensile strain barrier used and the In0.07GaAs compressive
      strain in MQWs. Through results based on InGaAs/GaAs MQWs, the highest output
      power of 6 mW was obtained at the In0.47GaP strain barrier, which shows a
      relative increase of almost 20% as compared to conventional MQWs.

PMID- 29448703
TI  - Exciton Formation Entropy Changes in Transition Metal Dichalcogenide Atomic
      Layers.
AB  - The atomic layers of transition metal dichalcogenides (TMDCs, MX2; M = Mo or W; X
      = S, Se, or Te) are of great interest in the areas of photonics and
      optoelectronics due to the correlation between valley orbital, spin, and optical
      helicity; the compositional tuning of exciton bandgaps in visible and near
      infrared spectra; and the bandgap modification from indirect for bilayer or
      multilayer to direct for monolayer. The derivative of the O'Donnell and Chen
      relation is analyzed as a function of temperature and gives the relationship
      between the change in entropy of exciton formation and the bandgap energy. The
      analysis suggests the change in entropy of exciton formation with higher energy
      phonons (~100 meV) is constant until ~90 K while lower energy phonons (~10 meV)
      approaches a constant value of -2skB between ~250 K and ~300 K where s is the
      strength of electron-phonon interaction and kB is the Boltzmann constant.
      Increased scattering and spontaneous decay probabilities explains the amplified
      electron-phonon interaction when the phonon energy is large. The change in
      exciton formation entropy can be increased ~3-fold while the bandgap is managed
      through the electron-phonon coupling strength.

PMID- 29448704
TI  - Characteristics of the Li-Ni Doped Cobalt Oxide Thin Films Prepared by Pulsed
      Laser Deposition.
AB  - Cobalt oxide spinel thin films doped with Ni and Li were deposited on c-sapphire
      single crystal substrates at various substrate temperatures and oxygen partial
      pressures by pulsed laser deposition. The effects of the doping and processing
      parameters on the crystal structure, electrical and optical properties of cobalt
      oxide base spinel thin films were analyzed by XRD, four point probe and UV
      spectrometry. The electrical conductivity increased with increasing Ni doping
      concentration, x, up to x = 0.7. The thin films grew on the sapphire substrates
      with a strong (111) preferred orientation. Li0.1Ni0.6Co2.3O4 spinel phase
      decomposed to a rock salt phase when the oxygen partial pressure was lower than 5
      mtorr. The electrical conductivity decreased rapidly with the formation of a rock
      salt phase due to the limited charge transfer between the divalent and trivalent
      cations.

PMID- 29448705
TI  - Dimerization of Ethylene to Butenes Over Ordered Mesoporous Silica SBA-15
      Supported Ni-Al Catalysts with Different Morphologies.
AB  - A series of ordered mesoporous silica (OMS) SBA-15 supports with different
      morphologies were prepared by different synthetic methods to investigate the
      effect of the characteristics of the morphology of OMS on the ethylene
      dimerization outcomes. After additions of Ni and Al species into the SBA-15
      support, a dimerization reaction of ethylene was performed using a fixed-bed
      reactor. Rod-type Ni-Al-SBA-15 with a small micron size showed better catalytic
      performance compared to those of the other catalysts. From these catalytic
      results, the particle size and morphology of a SBA-15 support critically
      influenced the catalytic activities and lifetimes of the dimerization catalysts.
      The optimum reaction pathway in the Ni-Al-SBA-15 catalyst enhanced the overall
      catalytic performance due to the suppression of the further oligomerization of
      ethylene and butenes. Moreover, ethylene dimerization was investigated over the
      rod-type Ni-Al-SBA-15 catalyst to discover an optimum reaction condition. The
      maximum yield of butenes was 24.7% at 300  degrees C at 11.5 bar with a WHSV of
      1.5 h-1.

PMID- 29448706
TI  - Visible Light Photocatalytic Performance of In Situ Synthesized Graphite-SiO2
      TiO2 Composite Towards Degradation of Benzene Gas.
AB  - Graphite-SiO2-TiO2 composites with optimum graphite and SiO2 loadings were
      prepared by a facile one-pot chemical route. The structural, morphological and
      physiochemical properties of the samples were investigated by analytical
      techniques. UV-Vis-DRS analysis confirmed light absorbance edge of composites was
      sharply red-shifted to the visible region with increasing graphite and SiO2
      content. The prepared composites showed higher photocatalytic activity towards
      degradation of benzene gas under visible light. The contribution of graphite and
      SiO2 on the enchantment of visible light photocatalytic performance of the
      composites was discussed.

PMID- 29448707
TI  - Surface Roughness of a 3D-Printed Ni-Cr Alloy Produced by Selective Laser
      Melting: Effect of Process Parameters.
AB  - The selective laser melting (SLM) process parameters, which directly determine
      the melting behavior of the metallic powders, greatly affect the nanostructure
      and surface roughness of the resulting 3D object. This study investigated the
      effect of various laser process parameters (laser power, scan rate, and scan line
      spacing) on the surface roughness of a nickel-chromium (Ni-Cr) alloy that was
      three-dimensionally (3D) constructed using SLM. Single-line formation tests were
      used to determine the optimal laser power of 200 W and scan rate of 98.8 mm/s,
      which resulted in beads with an optimal profile. In the subsequent multi-layer
      formation tests, the 3D object with the smoothest surface (Ra = 1.3 MUm) was
      fabricated at a scan line spacing of 60 MUm (overlap ratio = 73%). Narrow scan
      line spacing (and thus large overlap ratios) was preferred over wide scan line
      spacing to reduce the surface roughness of the 3D body. The findings of this
      study suggest that the laser power, scan rate, and scan line spacing are the key
      factors that control the surface quality of Ni-Cr alloys produced by SLM.

PMID- 29448708
TI  - High-Speed Growth of ZnO Nanorods in Preheating Condition Using Microwave
      Assisted Growth Method.
AB  - In this study, we present the microwave-assisted growth (MAG) of ZnO nanorods
      (ZNRs) using a preheating hydrothermal method under tailored preheating and
      postheating growth conditions. The perimeters such as solution concentration,
      preheating time, and postheating time, were changed to optimize ZNR growth and
      the growth was carried out in a domestic 850 watt microwave oven. Preheated
      solution was utilized as an accelerator to increase the aspect ratio of the ZNRs
      and reduce the fabrication time. Because of a long fabrication time and limited
      length in the conventional MAG method, preheating condition was used for
      efficient growth of nanorods through homogeneous nucleation in the solution and
      then heterogeneous nucleation of the formed ZNRs on seeded substrate during
      postheating process. The nanostructures were characterized with scanning electron
      microscopy to look at the morphology and dimensions. Dimensions of ZNRs kept on
      increasing as the molar concentration went higher. Preheating time highly
      affected the morphology, dimensions, and aspect ratio of ZNRs and postheating
      time not only ensured the stability of ZNRs with substrate due to heterogeneous
      nucleation process but also influenced the morphology of ZNRs.

PMID- 29448709
TI  - Cavitation Erosion Behavior of Electroless Ni-P Coating and Optimization of
      Process Parameter Using Analysis of Variance with Orthogonal Array.
AB  - This study investigated the cavitation erosion resistance of electroless Ni-P
      (EN) coated gray cast iron (GCI) in seawater solution. Furthermore, the optimum
      coating design parameters were examined to minimize cavitation erosion damage
      through analysis of variance (ANOVA) based on the L9 orthogonal array. In this
      study, four coating design factors were used: concentration of source of nickel
      (A), concentration of reducer agent (B), deposition temperature (C), and pressure
      of shot peening (D). In accordance with the regulation of the modified ASTM G32,
      the cavitation erosion experiment was conducted for 1 hour in a seawater solution
      to find the optimum design parameters which can minimize the cavitation erosion
      damage. Besides, ANOVA was performed to verify the contribution of each coating
      design parameter. As a result, the concentration of reducer agent among the EN
      process parameters was determined as the most significant factor in the
      cavitation erosion behavior.

PMID- 29448710
TI  - Preparation and Properties of WC-Based Alloy Coatings with Controlled Co and Cr
      via High Velocity Oxy-Fuel Spray Technique.
AB  - WC based alloy coatings included different mass percent of Co and Cr have been
      synthesized on high carbon steel by using a facile high velocity oxy-fuel spray
      method. The mechanical nature of the coating films has been investigated by micro
      vickers hardness and fracture toughness. X-ray diffraction (XRD) and EDX analyses
      indicate that the three different samples (WC-10Co-4Cr, WC-17Co, and WC-12Co)
      consist of pure WC, W, Cr, and Co constituents as well as W2C and Co6W6C phases.
      The SEM and image analysis results show that WC-10Co-4Cr condition has higher
      porosity than those of WC-17Co, and WC-12Co coatings. WC-17Co coating showed the
      highest value in the hardness and fracture toughness test among three different
      samples. The obtained results revealed that the mechanical properties of WC based
      alloy coatings synthesized by a facile high velocity oxy-fuel spray method is
      very sensitive to Co content.

PMID- 29448711
TI  - Investigation of Gate-Stacked In-Ga-Zn-O TFTs with Ga-Zn-O Source/Drain
      Electrodes by Atmospheric Pressure Plasma-Enhanced Chemical Vapor Deposition.
AB  - Atmospheric pressure plasma-enhanced chemical vapor deposition (AP-PECVD) was
      employed for the fabrication of indium gallium zinc oxide thin-film transistors
      (IGZO TFTs) with high transparent gallium zinc oxide (GZO) source/drain
      electrodes. The influence of post-deposition annealing (PDA) temperature on GZO
      source/drain and device performance was studied. Device with a 300  degrees C
      annealing demonstrated excellent electrical characteristics with on/off current
      ratio of 2.13 * 108, saturation mobility of 10 cm2/V-s, and low subthreshold
      swing of 0.2 V/dec. The gate stacked LaAlO3/ZrO2 of AP-IGZO TFTs with highly
      transparent and conductive AP-GZO source/drain electrode show excellent gate
      control ability at a low operating voltage.

PMID- 29448712
TI  - A Simulated Body Fluid Evaluation of TiO2 Barrier Oxide Layer Formed by
      Electrochemical Reaction.
AB  - The modified surface during implantation is considered to be an effective
      strategy to improve high adhesion of bone cell and osseointegration activity. In
      this paper, the TiO2 barrier oxide Layer has been fabricated by using the ion
      characteristic of an electrolytic solution, the surface characteristics have been
      investigated by EDS, XPS, and FE-SEM. From the analysis of the chemical states,
      phosphorus and calcium were observed in the TiO2 barrier layer, which were
      penetrated from the electrolyte into the oxide layer during deposit process. In
      addition, Ca 2p spectrum was identified into two peaks for Ca 2p3/2 and 2p1/2 at
      347.4 and 351.3 eV, which are related to hydroxyapatite. Also, P spectrum was
      confirmed into two peaks for P1/2 and P3/2 levels with binding energy 134.2 and
      133.4 eV, respectively. Thus, the incorporated phosphate species were found
      mostly in the forms of HPO-4, PO-3. From the result of biological evaluation in
      simulated body fluid (SBF), the apatite morphologies were effective for bioactive
      property on the modified surface.

PMID- 29448713
TI  - Study on Microstructure and Mechanical Properties of Al-Li Based Alloys Processed
      by Extrusion.
AB  - Aluminum and its alloys, due to their low density, high specific strength and
      high corrosion resistance amongst various structural materials, are used in a
      wide range of industrial applications for different aqueous solutions. In the
      present study, we studied effects of Ce addition on microstructure and mechanical
      properties of Al-2Li-1Cu-0.8Mg-0.1Zr alloys. The melt was held at 780  degrees C
      for 20 min and poured into a mold. And as-cast Al alloys were hot-extruded into a
      plate that was 4 mm in thickness with a reduction ratio of 14:1. The extruded
      plates were held at 540  degrees C for 4 hr in water quenching to solution
      treatment them. As-extruded Al-2Li-1Cu-0.8Mg-0.1Zr-xCe (x = 0.3, 0.6, 0.9 and 1.2
      wt.%) alloys are composed of Al, AlLi, AlCuLi and Al11Ce3 phases. By increasing
      the Ce content from 0 to 1.2 wt.%, the Al11Ce3 phase is increased, after solution
      treatment the AlLi and AlCuLi phases are decreased. With increasing Ce addition
      from 0 to 1.2 wt.%, the average grain size of the as-extruded Al alloys were
      decreased slightly from 100.7, 113.74, 84.3, 74.7 and 61.7 MUm and ultimate
      tensile strength was decreased slightly from 267.59, 264.92, 237.40, 220.93 and
      207.83 MPa at room temperature. After solution treatment, ultimate tensile
      strength was measured with 205.13, 198.12, 195.50, 198.27 and 208.01 MPa at room
      temperature.

PMID- 29448714
TI  - In Situ Template-Synthesis of Hollow CeO2 Nanobeads in scCO2 with Improved
      Catalytic Activity Towards CO Oxidation.
AB  - A green and robust route by in-situ generation of CeO2 beads around the carbon
      nanotubes (CNTs) in supercritical carbon dioxide (scCO2) was developed in this
      work to synthesize hollow CeO2 nanobeads with improved catalytic activity for CO
      oxidation.

PMID- 29448715
TI  - Investigate on Structure and Optical Properties of ZnO Nanostructures Grown on a
      GaN/r-Sapphire.
AB  - ZnO nanostructures were directly grown on a-GaN/r-sapphire with different growth
      time via aqueous method. Structural and optical properties of the nanostructures
      were investigated by using a variety of techniques including X-ray diffraction
      (XRD), scan electron microscope (SEM), room-temperature photoluminescence (PL),
      and Raman scattering. The results showed the growth mechanism of ZnO
      nanostructures grown on a-GaN is Volmer-Weber (VW) mode, which is due to the high
      interfacial free-energy between a-plane ZnO and GaN. Meanwhile, compressive
      strains were revealed to exist by the optical characterizations. And the
      strengths were found to reduce with increasing growth time.

PMID- 29448716
TI  - Templated Growth of Pd Nanoparticles Using Sputtering Deposition Process and Its
      Catalytic Activities.
AB  - A simple method based on sputtering deposition of Pd onto mesoporous SiO2 (SBA
      15) was employed to produce supported Pd nanoparticles (NPs) that can be used as
      hydrogenation catalysts. The use of sputtering deposition eliminates contaminants
      and avoids additional drawbacks of traditional chemical methods applied to
      prepare heterogeneous supported metal catalysts. A mechanical resonant stirrer
      was used to revolve the SBA-15 powder and ensure homogeneous distribution of the
      Pd NPs over the support. The SBA-15 pores act as templates for Pd NPs and drive
      nanostructure growth. Consequently, the NPs obtained have the same diameter as
      that of the SBA-15 channels (~5 nm) and elongated particles are formed as
      sputtering deposition increases. The SBA-15 supported Pd NPs (Pd NPs/SBA-15) were
      tested in a probe hydrogenation of cyclohexene reaction to evaluate the catalytic
      activity of the Pd NPs. Turnover frequency (TOF) of 2000 min-1 were achieved with
      the lower Pd NPs concentration (0.15 wt%) catalyst.

PMID- 29448717
TI  - Effect of UVB Light Exposure on Tensile Behavior of Carbon Nanotube Sheet.
AB  - The effects of ultraviolet B (UVB) exposure on the tensile behavior of CNT sheet
      was investigated in this study. Two types of CNT sheet, one acid treated and one
      un-treated, were directly exposed to UVB light for 500 hours. The exposure was
      done using a UVB lamp inside a dark chamber under room temperature ambient
      condition. The microstructure of the CNT sheets were studied both prior to and
      after UVB exposure using a scanning electron microscope. Upon completion of the
      exposure duration, the CNT sheet test coupons were tested mechanically in tension
      using a microtester to evaluate the tensile strength and behavior. The results
      were compared to those of the CNT sheet test coupons that were not exposed to UVB
      light. It was observed that the strength of the acid treated CNT sheet decreased
      after UVB exposure while the strength of the un-treated CNT sheet increased.
      Apart from slight changes in stiffness, the overall mechanical behavior with
      increasing applied load did not show much change after the exposure to UVB light.
      The microscopic analysis showed evidences of morphological changes in the CNT
      microstructure upon UVB exposure. These changes supported the change in
      mechanical strength as a result of the UVB exposure.

PMID- 29448718
TI  - Conductance Measurement of Pyrazine Molecular Junction with Cu and Ag Electrodes.
AB  - We have measured the conductance of pyrazine molecular junction contacting with
      Cu and Ag electrodes by using an electrochemical jump-to-contact based scanning
      tunneling microscopy break junction (ECSTM-BJ). While conductance values of 10
      2.8 and 10-3.7 G0 are measured for pyrazineCu electrode, 10-2.1 and 10-3.3 G0 are
      found for pyrazine-Ag contact. The result shows that the conductance of pyrazine
      with Ag electrode is larger than that with Cu electrode, which can contribute to
      the different efficiency of electron transport along the molecular junction
      between Ag and Cu electrodes. The current work shows the important role for the
      electrode material in electron transport.

PMID- 29448719
TI  - Cost-Effective Fabrication of Inner-Porous Micro/Nano Carbon Structures.
AB  - This paper reports the fabrication of a new micro/nano carbon architecture array
      which owns the characteristics of inner-porous, desired conductivity and large
      effective surface area. The micro/nano inner-porous carbon structures were
      fabricated for the first time, with ordinary and cost-effective processes,
      including photolithography, oxygen plasma etching and pyrolysis. Firstly,
      micro/nano hierarchical photoresist structures array was generated through
      photolithography and oxygen plasma etching processes. By introducing a critical
      thin-film spin-coating step, and followed with carefully pyrolyzing process, the
      micro/nano photoresist structures were converted into innerporous carbon
      architectures with good electric connection which connected the carbon structures
      array together. Probably the inner-porous property can be attributed to the
      shrinkage difference between positive thin film and negative photoresist
      structures during pyrolyzing process. It is demonstrated that the simple method
      is effective to fabricate inner-porous carbon structures with good electric
      connection and the carbon structures can be used as electrochemical electrodes
      directly and without the addition of other pyrolysis or film coating processes.
      The electrochemical property of the carbon structures has been explored by cyclic
      voltammetric measurement. Compared with solid carbon microstructures array, the
      cyclic voltammetry curve of inner-porous carbon structures shows greatly enhanced
      current and improved charge-storage capability, indicating great potential in
      micro energy storage devices and bio-devices.

PMID- 29448720
TI  - Probing an Individual Electron Spin State in a Quantum Dot with Spin Bias.
AB  - A quantum dot coupled to two electrodes with spin-dependent splitting of chemical
      potentials (spin bias) is proposed as a detector of an individual electron spin.
      Spin polarized transport properties through the quantum dot have been
      investigated theoretically by means of the nonequilibrium Green's function
      formalism. We found that the direction of current flow is dependent on the
      electronic spin state in quantum dot. Measuring the direction of the current flow
      through the devices, we can determine the direction of the electronic spin state
      in quantum dot. This proposed detector provides a practical and all electrical
      approach to detect the electronic spin state in quantum dot structure.

PMID- 29448721
TI  - Oxidation and Tribological Behavior of Ti-B-C-N-Si Nanocomposite Films Deposited
      by Pulsed Unbalanced Magnetron Sputtering.
AB  - Quinary Ti-B-C-N-Si nanocomposite films were deposited onto AISI 304 substrates
      using a pulsed d.c. magnetron sputtering system. The quinary Ti-B-C-N-Si (5 at.%)
      film showed excellent tribological and wear properties compared with those of the
      Ti-B-C-N films. The steady friction coefficient of 0.151 and a wear rate of 2 *
      10-6 mm3N-1m-1 were measured for the Ti-B-C-N-Si films. The oxidation behavior of
      Ti-B-C-N-Si nanocomposite films was systematically investigated using X-ray
      diffraction (XRD), and thermal analyzer with differential scanning calorimetry
      (DSC) and thermogravimetric analysis (TGA). It is concluded that the addition of
      Si into the Ti-B-C-N film improved the tribological properties and oxidation
      resistance of the Ti-B-C-N-Si films. The improvements are due to the formation of
      an amorphous SiOx phase, which plays a major role in the self-lubricant tribo
      layers and oxidation barrier on the film surface or in the grain boundaries,
      respectively.

PMID- 29448722
TI  - Characterization of Pulse Reverses Electroforming on Hard Gold Coating.
AB  - Effect of pulse reverse current (PRC) method on brass coatings electroplated from
      gold solution was investigated by various plating parameters such as plating
      duration, the anodic duty cycle, the anodic current density and the cathodic
      current density. The reversed current results in a significant change in the
      morphology of electrodeposits, improvement of the overall current efficiency and
      reduction of deposit porosity. With longer pulses, hemispherical surface features
      are generated, while larger grains result from shorter pulse widths. The porosity
      of the plated samples is found to decrease compared with results at the same time
      average plating rate obtained from DC or Pulse plating. A major impediment to
      reducing gold later thickness is the corrosion of the underlying substrate, which
      is affected by the porosity of the gold layer. Both the morphology and the
      hydrogen evolution reaction have significant impact on porosity. PRC plating
      affect hydrogen gold and may oxidize hydrogen produced during the cathodic
      portion of the waveform. Whether the dissolution of gold and oxidation of
      hydrogen occur depends on the type of plating bath and the plating conditions
      adapted. In reversed pulse plating, the amount of excess near-surface cyanide is
      changed after the cathodic current is applied, and the oxidation of gold under
      these conditions has not been fully addressed. The effects of the current
      density, pulse-reverse ratio and brightener concentration of the electroplating
      process were investigated and optimized for suitable performance.

PMID- 29448723
TI  - Preparation of Nanoscale Zinc Oxide-Laponite Composites by Polyvinyl Alcohol
      Polymerization and Usability for Removal of Trichloroethylene in Water.
AB  - Innovative nanoscale ZnO-laponite-polyvinyl alcohol composites (NZLPc) were
      developed as a valid alternative to nanoscale photocatalysts for mineralization
      of chlorinated hydrocarbons without difficulties in recovery of nanoscale
      photocatalyst particles. NZLPc were synthesized by mixing nanoscale ZnO particles
      with laponite in PVA solution, and by crosslinking PVA solution in the presence
      of boric acid (>=1.6 M). Different mixing ratios of the raw materials were
      investigated to develop the stable NZLPc, and X-ray diffraction, scanning
      electron microscopy, energy-dispersive X-ray spectroscopy, and transmission
      electron microscopy characterizations were performed. From the results, a
      3:1:1:10 ratio of ZnO, laponite, PVA, and deionized water by weight was
      appropriate to form spherical NZLPc with high porosities and enhanced mechanical
      strengths. Also, the degradation efficiencies of trichloroethylene were
      significantly improved with both NZLPc and UV irradiation, indicating that ZnO
      mediated heterogeneous photocatalytic degradation occurred. Thus, the proposed
      synthesis of NZLPc paves a way for the economical and effective photocatalytic
      approach to remove the recalcitrant organic compounds in water through the
      multiple reaction processes (i.e., sorption, photolysis, and photocatalysis).

PMID- 29448724
TI  - Environmental Applications of Nano-Sized Recycled Aggregates: The Effect of
      Sterilization and Adsorption.
AB  - To evaluate the sterilize efficiency of nano-sized recycled aggregates (RAs),
      several types of RAs were examined for the purpose of environmental stamping out
      procedure. The poultry (e.g., chicken) was selected as a target livestock of
      epidemic disease, and the blast furnace slag (BFS), fly ash (FA), slaked lime
      (SL), nano-cerium (n-Ce) and shell (Sh) were used as the RAs materials. The
      fermented solution of effective microorganisms (EM) was added to decompose the
      target livestock. Various kinds of lab-scale reactor were operated to examine the
      effects of RAs volume; high and low volume of RAs (e.g., 1.89 w/v% and 1.14 w/v%
      of RA in solution, respectively), and the effects of EM concentration (e.g.,
      concentrated solution (100%) and diluted solution (12.5%)) with tested in
      different reaction time. The number of microorganisms after batch tests was
      counted for the sterilized effects of RAs, and organic matters (e.g., chemical
      oxygen demand (COD)) and inorganic matters (e.g., suspended solids (SS), heavy
      metals and potential ions) were analyzed before and after adsorption process. The
      cases of SL and n-Ce showed high removal of microorganism in the batch of high
      concentrated EM for 20 days. However the other RA materials were less effective
      on the sterilization especially in lower volume of RAs. In diluted EM (e.g.,
      12.5%) tests, most RAs have high sterilization efficiencies in the short periods
      of batch reaction regardless of RAs types, and it was more effective with longer
      reaction time. The BFS and n-Ce exhibited higher surface area than others and
      they adsorbed highly heavy metals in water. The results suggested that the
      concentration of target organism was the most important to determine
      sterilization and adsorption properties of RAs.

PMID- 29448725
TI  - AuAg Bimetallic Non-Alloyed Nanoparticles on SiO2 Spacer Layer for Improved Light
      Absorption in Thin-Film c-Si Solar Cells.
AB  - We present a light trapping structure consisting of gold and silver (AuAg)
      bimetallic non-alloyed nanoparticles (BNNPs) on a silicon dioxide (SiO2) spacer
      layer over crystalline silicon (c-Si) film, designed to improve the absorption of
      thin-film c-Si solar cells. Prior to fabrication of the AuAg BNNPs on the SiO2
      spacer layer, numerical investigations were carried out using electromagnetic
      field simulation following the finite-difference time-domain method. The
      hemispherical Au8Ag8 BNNPs were fabricated and deposited on a 15 nm-thick SiO2
      spacer layer, which enhanced light trapping in the c-Si film over a broad
      wavelength range (450-1100 nm). Specifically, more than 85% of the incident light
      was absorbed in the c-Si film at 620 nm wavelengths due to the strong scattering
      of the Au8Ag8 BNNPs. To the best of our knowledge this is the first case
      presenting such a theoretical calculation and experimental study of the efficient
      light trapping by AuAg BNNPs on space layer for increasing the absorption in thin
      film c-Si solar cells.

PMID- 29448726
TI  - Effects of Intermetallic Compound Formation in Al/Cu Clad Material Fabricated by
      Differential Speed Rolling.
AB  - In this study, the microstructure and mechanical property of Al/Cu clad material
      fabricated by differential speed rolling at room temperature were evaluated. Al
      and Cu plates were prepared and mechanically cladded at a differential speed
      ratio of 2:1 between the upper and lower rolls. Post- heat-treatment was carried
      out after the mechanical cladding at 400  degrees C for 60 min to induce the
      formation of intermetallic compound layers at the bonded interface of Al/Cu. As a
      result, differential speed rolling afforded a soundly cladded interface without
      any defects such as voids and cracks. In addition, intermetallic compound layers
      such as Al4Cu9 and Al2Cu were formed at the mechanically bonded interface during
      post-heat-treatment for 60 min, which led to an increase in Vickers microhardness
      value more than 30% relative to the base material. Therefore, we systematically
      explained the relationship between formation of intermetallic compounds and
      mechanical property of Al/Cu clad materials in this study.

PMID- 29448727
TI  - NH4OH-Oriented and pH-Dependent Growth of ZnO Nanostructures via Microwave
      Assisted Growth Method.
AB  - We proffer NH4OH-oriented and pH-dependent growth of ZnO nanostructures via a
      microwaveassisted growth method. The fabrication of ZnO nanorods (ZNRs),
      nanoflowers (ZNFs), nanostars (ZNSs), and nanotetrapods (ZNTs) is presented.
      NH4OH was used as a mineralizer to change the solution pH for nanostructure
      growth, where temperature and other variables were fixed. Because of an efficient
      heat transfer and facile growth of nanostructures, a domestic microwave oven was
      used to facilitate the nanostructure growth in the span of just 10-15 min. The
      results showed that the growth of ZnO nanostructures was dependent upon the
      number of growth units and ZnO nuclei present in the solution, which ultimately
      depend upon the pH of the solution. At the outset, without the addition of NH4OH,
      the pH of the solution was ~6.8 and the ZNRs were formed in the solution or on a
      seeded substrate which persisted in the pH range of ~6.8-9. An abrupt change in
      the shapes and the types of the nanostructures was observed when the pH was
      boosted beyond 10. A transition from ZNRs to ZNFs was observed at pH 10 and ZNFs
      were formed at pH 11. The solution gave birth to ZNSs and ZNTs when the pH was
      further raised to 12 and 13, respectively.

PMID- 29448729
TI  - Development of Nanofiber Reinforced Double Layered Cabin Air Filter Using Novel
      Upward Mass Production Electrospinning Set Up.
AB  - Recently, numerous researchers are interested in the development of new air
      filter because of air pollution caused by rapid industrialization and
      urbanization. The major concerns in developing air filters are: pressure drop and
      filtration efficiency which are considered significant. As the pressure drop
      increases, the energy consumption becomes high. In this study, we developed a
      novel air filter (polyurethane fiber mat) for nano size filtration using a mass
      production electrospinning, which is expected to enhance filtration efficiency
      and pressure drop effects. To determine the optimal electrospinning conditions
      for filter efficiency, various concentrations (8, 10, 12 wt/wt%) of thermoplastic
      polyurethane were prepared and employed. Scanning electron microscope (SEM) and
      Fourier transform infrared spectroscopy (FT-IR) were used for fiber
      characterization, and finally, efficiency test was conducted to evaluate the
      filter performance of developed nanofiber-based air filter. From this study, it
      could be concluded that optimization by adjusting the polymer concentration and
      electrospinning operating condition was the best efficient alternative method to
      fabricate nano-fibrous air filter system with improved filtration performance.

PMID- 29448728
TI  - Carbon Nanostructure of Diesel Soot Particles Emitted from 2 and 4 Stroke Marine
      Engines Burning Different Fuels.
AB  - Diesel soot particles were sampled from 2-stroke and 4-stroke engines that burned
      two different fuels (Bunker A and C, respectively), and the effects of the engine
      and fuel types on the structural characteristics of the soot particle were
      analyzed. The carbon nanostructures of the sampled particles were characterized
      using various techniques. The results showed that the soot sample collected from
      the 4-stroke engine, which burned Bunker C, has a higher degree of order of the
      carbon nanostructure than the sample collected from the 2-stroke engine, which
      burned Bunker A. Furthermore, the difference in the exhaust gas temperatures
      originating from the different engine and fuel types can affect the nanostructure
      of the soot emitted from marine diesel engines.

PMID- 29448730
TI  - Effects of Fragmented Fe Intermetallic Compounds on Ductility in Al-Si-Mg Alloys.
AB  - Fe is intentionally added in order to form the Fe intermetallic compounds (Fe
      IMCs) during casting. Field emission scanning electron microscope with energy
      dispersive spectrometer (EDS) was conducted to understand microstructural changes
      and chemical composition analyses. The needlelike Fe-IMCs based on two
      dimensional observation with hundreds of micro size are modified to fragmented
      particles with the minimum size of 300 nm through clod rolling with 80% thickness
      reduction. The ratio of Fe:Si on the fragmented Fe-IMCs after 80% reduction is
      close to 1:1, representing the beta-Al5FeSi. The yield and tensile strengths are
      increased with increasing reduction rate. On the other hand, the elongation is
      decreased with the 40% reduction, but slightly increased with the 60% reduction.
      The elongation is dramatically increased over two times for the specimen of 80%
      reduction compared with that of the as-cast. Fracture behavior is strongly
      affected by the morphology and size of Fe-IMCs. The fracture mode is changed from
      brittle to ductile with the microstructure modification of Fe-IMCs.

PMID- 29448731
TI  - Role of the Growth Temperature in MoS2 Growth by Chemical Vapor Deposition.
AB  - In this paper, we discuss the effect of synthesis temperature on the lateral
      growth of MoS2 thin films in chemical vapor deposition. With increasing
      temperature, surface coverage with MoS2 triangular islands is significantly
      improved due to an increase in the density of nuclei and fully continuous MoS2
      thin film is grown when the growth temperature reached 800  degrees C. The MoS2
      triangular islands grown at the temperature from 650 to 750  degrees C are
      monolayer and highly crystalline, whereas the large-area continuous film grown at
      the temperature of 800  degrees C is composed of double-layer or overlapping MoS2
      nanosheets. Our research provides that synthesis temperature is the key to growth
      large area and high quality single crystal MoS2 films.

PMID- 29448732
TI  - Hot Deformation Behavior of Hot-Extruded AA7175 Through Hot Torsion Tests.
AB  - The hot deformation behavior of hot-extruded AA7175 was investigated with flow
      curves and processing maps through hot torsion tests. The flow curves and the
      deformed microstructures revealed that dynamic recrystallization (DRX) occurred
      in the hot-extruded AA7175 during hot working. The failure strain was highest at
      medium temperature. This was mainly influenced by the dynamic precipitation of
      fine rod-shaped MgZn2. The processing map determined the optimal deformation
      condition for the alloy during hot working.

PMID- 29448733
TI  - Quantitative Image Analysis of Carbon Nanostructure of Particles Produced from
      Combustion Process.
AB  - In the present study, the soot particles produced from diffusion flames burning
      biodiesel fuel were thermophoretically sampled and the carbon nanostructure of
      soot particles were imaged using a high resolution transmission electron
      microscopy (HRTEM). The HRTEM images of soot particles were then quantitatively
      analyzed using a digital image processing algorithm developed and implemented as
      part of this work. The HRTEM interpretations with an aid of image processing
      support feasibility of use of the developed image processing technique for carbon
      nanostructure quantification.

PMID- 29448734
TI  - Wear Resistance Properties Reinforcement Using Nano-Al/Cu Composite Coating in
      Sliding Bearing Maintenance.
AB  - Sliding bearing maintenance is crucial for reducing the cost and extending the
      service life. An efficient and practical solution is to coat a restorative agent
      onto the worn/damaged bearings. Traditional pure-copper (Cu) coating results in a
      soft surface and poor abrasion resistance. To address this issue, this paper
      presents a nano-composite repairing coating method. A series of nano-Al/Cu
      coatings were prepared on the surface of 45 steel by composite electro-brush
      plating (EBP). Their micro-hardness was examined by a MHV-2000 Vickers hardness
      tester, and tribological properties by a UMT-2M Micro-friction tester, 3D
      profiler and SEM. Then, the influence of processing parameters such as nano
      particle concentration and coating thickness on the micro-hardness of nano-Al/Cu
      coating was analyzed. The experimental analysis results demonstrate that, when
      the nano-Al particle concentration in electrolyte was 10 g/L, the micro-hardness
      of the composite coating was 1.1 times as much as that of pure-Cu coating. When
      the Al nano-particle concentration in electrolyte was 20 g/L, the micro-hardness
      of the composite coating reached its maximum value (i.e., 231.6 HV). Compared
      with the pure-Cu coating, the hardness and wear resistance of the nano-composite
      coating were increased, and the friction coefficient and wear volume were
      decreased, because of the grain strengthening and dispersion strengthening. The
      development in this work may provide a feasible and effective nano-composite EBP
      method for sliding bearing repair.

PMID- 29448735
TI  - Fabrication of Up-Conversion Phosphor Films on Flexible Substrates Using a
      Nanostructured Organo-Silicon.
AB  - Up-conversion phosphors have attracted considerable attention because of their
      applications in solid-state lasers, optical communications, flat-panel displays,
      photovoltaic cells, and biological labels. Among them, NaYF4 is reported as one
      of the most efficient hosts for infrared to visible photon up-conversion of Yb3+
      and Er3+ ions. However, a low-temperature method is required for industrial scale
      fabrication of photonic and optoelectronic devices on flexible organic
      substrates. In this study, hexagonal beta-NaYF4: 3 mol% Yb3+, 3 mol% Er3+ up
      conversion phosphor using Ca2+ was prepared by chemical solution method. Then, we
      synthesized a nanostructured organo-silicon compound from methyl tri
      methoxysilane and 3-glycidoxy-propyl-trimethoxy-silane. The transmittance of the
      organo-silicon compound was found to be over 90% in the wavelength range of
      400~1500 nm. Then we prepared a fluoride-based phosphor paste by mixing the
      organo-silicon compound with Na(Ca)YF4:Yb3+, Er3+. Subsequently, this paste was
      coated on polyethylene terephthalate, followed by heat-treatment at 120  degrees
      C. The visible emission of the infrared detection card was found to be at 655 nm
      and 661 nm an excitation wavelength of 980 nm.

PMID- 29448736
TI  - Synthesis and Electroluminescence Properties of New Type Multi-Chromophore
      Emitting Materials for Organic Light-Emitting Diodes.
AB  - New three emitting compounds, AK-1, AK-2 and AK-3 including diazocine moiety were
      synthesized through Suzuki-coupling reaction. Physical properties such as
      optical, electroluminescent properties were investigated. UV-visible spectrum of
      AK-1, AK-2 and AK-3 in film state showed maximum 392, 393 and 401 nm. PL spectrum
      of AK-1, AK-2 and AK-3 showed maximum emission wavelength of 472, 473 and 435 nm.
      Three compounds were used as EML in OLED device: ITO/2-TNATA (60 nm)/NPB (15
      nm)/EML (35 nm)/Alq3 (20 nm)/LiF (1 nm)/Al (200 nm). AK-3 OLED device showed
      C.I.E value of (0.18, 0.26) and luminance efficiency of 0.51 cd/A at 10 mA/cm2.
      New derivatives including diazocine moiety were introduced as OLED emitting
      material and the EL efficiency was increased by the proper combination of core
      and side group.

PMID- 29448737
TI  - Synthesis and Electroluminescence Properties of New Dual-Core Derivatives.
AB  - New blue emitting materials based on dual core concept, TP-AF-TP and TP-HAF-TP
      were synthesized through boronylation and Suzuki coupling reactions. In the thin
      film state, TP-AF-TP and TP- HAF-TP exhibited maximum PL values at 445 and 440
      nm, respectively. A non-doped OLED device based on TP-AF-TP and TP-HAF-TP showed
      current efficiency of 3.16 and 2.67 cd/A, respectively. TP-AF-TP exhibited a
      higher EL efficiency than that of TP-HAF-TP.

PMID- 29448738
TI  - Synthesis and Electroluminescent Properties of New Dibenzo-Diazocine Derivatives.
AB  - AK-1NA and AK-2NA based on dibenzo-diazocine and anthracene moieties were
      designed and synthesized. Normalized UV-visible spectra of AK-1NA and AK-2NA in
      film state showed maximum absorption wavelength of 394 and 393 nm. PL spectra of
      AK-1NA and AK-2NA showed maximum emission wavelength of 429 and 444 nm. At a
      current density of 10 mA/cm2, OLED devices of AK-1NA and AK-2NA exhibited
      luminance efficiency of 2.39 and 1.50 cd/A, power efficiency of 1.01 and 0.81
      lm/W. Also, OLED devices of AK-1NA and AK-2NA devices exhibited CIE(x, y ) of
      (0.16, 0.22) and (0.23, 0.42).

PMID- 29448739
TI  - Bandgap Tunability of Transition Metal Dichalcogenide Atomic Layers.
AB  - The temperature-dependent bandgap of transition metal dichalcogenides (TMDCs,
      MX2; M = Mo or W; X = S, Se, or Te) is analyzed using the O'Donnell and Chen
      relation with parameters including the average acoustic phonon energy (<homega>)
      and the electron-phonon coupling strength (s). Wider (narrower) tunability of the
      bandgap results from the larger (smaller) electron-phonon coupling strength for a
      constant acoustic phonon energy. A 1.5 eV bandgap change was observed for weak
      electron-phonon coupling (s = 2) as well as with the strong electron-phonon
      coupling (s = 30). However, the weak electron-phonon coupling leads to a linear
      decrease in the bandgap energy as a function of temperature above ~85 K while the
      strong coupling exhibits similar behavior after ~60 K. Narrower (wider)
      tunability of the bandgap results from the larger (smaller) acoustic phonon
      energy for a constant electron-phonon coupling strength. The slope of negative
      entropy of exciton formation is large (small) at lower (higher) temperature. The
      management of the electron-phonon interaction as well as the average acoustic
      phonon energy indicates the ability to control the bandgap.

PMID- 29448740
TI  - Effect of Intermetallic Compound Formation in Friction Welded Al Alloy Rods.
AB  - This study was carried out to evaluate the development of microstructures and
      mechanical properties on friction welded dissimilar materials with a light
      weight. For this work, Al6063 and Duralumin alloys with a shape of rod were
      selected as experimental materials, and friction welding was performed under
      conditions with a rotation speed of 2,000 RPM, a friction load of 12 kgf/cm2 and
      an upset force of 25 kgf/cm2, respectively. After welding, the microstructural
      analysis such as the grain boundary characteristic distributions and the
      formation of intermetallic compounds was analyzed by electron back-scattering
      diffraction method and transmission electron microscopy, respectively. In
      addition, the evaluation of mechanical properties on welded materials was
      conducted by Vickers microhardness and tensile test. As a result, applying the
      friction welding led to the significant grain refinement from 50 MUm in base
      material to 2 MUm in welded zone, respectively. In case of mechanical properties,
      Vickers micro-hardness and tensile strength of the welded material occupied 81%
      and 96% in fraction relative to the base material, respectively, which was
      attributable to the formation and growth of intermetallic compounds during the
      welding.

PMID- 29448741
TI  - Facile Synthesis and Characterization of Zinc Oxide Nanoparticle on Activated
      Carbon Using Liquid Phase Plasma Method.
AB  - Zinc oxide/activated carbon nanocomposites were synthesized by impregnating zinc
      oxide nanoparticles onto activated carbon powder using liquid phase plasma (LPP)
      method. Zinc oxide nanoparticles on the surface of activated carbon were
      fabricated rapidly by the LPP method due to reducing the zinc ion in aqueous
      solution. The obtained zinc oxide/activated carbon nanocomposites were
      characterized by XPS, HRTEM, and EDS. The amount of zinc oxide nanoparticles
      impregnated increased with increasing initial precursor concentration.
      Approximately 150~300 nm sized spherical shaped nanoparticles were uniformly
      dispersed on the surface of activated carbon powder.

PMID- 29448742
TI  - NO2 Gas Sensing Properties of Nano-Sized WO3 Powders Prepared by a Polyvinyl
      Alcohol Solution Route.
AB  - Nano-sized tungsten oxide (WO3) powder shows excellent sensitivity as a NOx gas
      sensor. The tungsten oxide powders synthesized by polyvinyl alcohol (PVA) polymer
      solution method showed either plates or spheres of tungsten nanoparticles with
      agglomeration. The size of the particles was about 30 nm and the surface areas of
      the powders fell in 10.5~21.5 m2/g. For NO2 gas sensing test, the synthesized WO3
      powders have been operated under various temperatures and gas concentrations. The
      response time, recovery time and stability were strongly depended on the powder
      size and morphology. The nano-sized WO3 powders showed relatively fast response
      and high reproducibility.

PMID- 29448743
TI  - Effects of Mg Addition with Natural Aging Time on Two-Step Aging Behavior in Al
      Mg-Si Alloys.
AB  - Influence of Mg contents with the natural aging (NA) time on the two-step aging
      behavior in Al-Mg-Si alloys is studied. Hardness is gradually increased during NA
      in the 3M4S, whereas dramatic increase of hardness after NA for 3.6 ks is
      confirmed in the 9M4S. Similar peak hardness is confirmed between the two-step
      aged and single aged samples in the 3M4S. It means that there is no negative
      effect of two-step aging. On the other hand, the peak hardness is decreased for
      the naturally-aged sample compared with the single aged one in the 9M4S.
      Formation of Cluster (1) is accelerated by the Mg addition, resulting in the
      negative effect of two-step aging. Meanwhile, the formation of the precipitates
      is accelerated by Mg addition during aging at 170  degrees C. The precipitate
      formed at the peak hardness during aging at 170  degrees C after natural aging
      for 43.2 ks is identified as the beta" phase based on the high resolution
      transmission electron microscope observation.

PMID- 29448744
TI  - The Effects of Dy Addition on Microstructure and Mechanical Properties of the As
      Cast Mg-5Al-3Ca-2Nd Alloys.
AB  - The microstructure of the as-cast Mg-5Al-3Ca-2Nd-xDy alloys consists of alpha-Mg
      matrix, (Mg, Al)2Ca eutectic phase, Al-Nd and Al-Dy intermetallic compounds.
      alpha-Mg matrix morphology was changed from dendritic to equiaxed with the
      increase Dy addition. And grain size was remarkably refined. As Dy content was
      increased, yield strength was improved due to the refined grains and the
      homogeneous distribution of Al-Dy phase.

PMID- 29448745
TI  - Nanostructured Biomass Based Carbon Materials from Beer Lees for Hydrogen
      Storage.
AB  - The present work describes the preparation of carbon materials from beer lees and
      their hydrogen adsorption abilities. Activated carbons (ACs) from beer lees were
      prepared through chemical activation using potassium hydroxide as an activating
      agent. The low temperature nitrogen adsorption isotherm studies on prepared ACs
      were conducted at 77 K to determine their physical properties and adsorption
      energy distribution. The beer lees based carbons have energetically heterogeneous
      surfaces and high surface area ranging from 1927-2408 m2/g. ACs prepared in this
      study show the gravimetric hydrogen adsorption capacity of 2.43-2.92 wt%
      depending on their physical properties.

PMID- 29448746
TI  - Nano Precipitation and Hardening of Die-Quenched 6061 Aluminum Alloy.
AB  - Die quenching is applied to an age-hardenable aluminium alloys to obtain super
      saturated solid solution. The application is advantageous because it can reduce
      number of manufacturing processes, and may increase strength by strain aging. If
      die quenching is realized in forging as well as sheet forming, it may widen
      industrial applicability further. In this study, Al-Mg-Si alloy AA6061 8 mm-thick
      billets were reduced 50% in height without cracks by die-quench forging.
      Supersaturated solid solution was successfully obtained. The die-quenched
      specimen shows higher hardness with nano precipitates at shorter aging time than
      the conventional water-quenched specimen.

PMID- 29448747
TI  - Addition of a Second Metal (Co) to Molybdenum Carbide: Effect of the Doping
      Route.
AB  - Molybdenum carbide is an interesting and versatile material, which has important
      applications in the metal matrix industry as a reinforcement material, as well as
      in the catalytic field. Though many papers suggest different methodologies for
      adding cobalt to the carbide structure aiming either to increase catalytic
      activity or enhancing mechanical proprieties such as ductility, etc. no
      straightforward evaluation is available. In the present paper two doping
      methodologies were studied: via solid state mixture of powders and via wet
      impregnation. Ammonium molybdate [(NH4)2MoO4] and cobalt nitrate [Co(NO3)2.6H2O]
      were used as starting materials and the doping process was carried out before
      carburization reaction. Those materials were characterized by FT-IR, SEM, XRF and
      XRD. The carbo-reduction products' were evaluated on XRD and XRF basis. Doped
      precursors' evaluation showed that the wet impregnated doped materials presented
      smaller particle sizes, were more homogeneous and retained more cobalt than the
      solid state doped ones. However, final products' assessment indicated that the
      solid state methodology was able to retain a greater dopant percentage according
      to XRF evaluation, and XRD data indicated a more intrinsic addition of the dopant
      to the carbide structure. In addition, no significant changes on particle size
      could be attributed to any of the methodologies, both producing Mo2C of
      approximately 30 nm.

PMID- 29448748
TI  - Soluble and Nanoporous Silica Gel-Entrapped C. freundii Methionine gamma-Lyase.
AB  - Methionine gamma-lyase is a pyridoxal 5'-phosphate dependent tetramer that
      catalyzes the alpha,gamma-elimination of methionine in ammonia, methanethiol and
      alpha-ketobutyrate. MGL catalytic power has been exploited as a therapeutic
      strategy to reduce the viability of cancer cells or bacteria. In order to obtain
      a stable enzyme to be delivered at the site of action, MGL can be encapsulated in
      a variety of matrices. As a reference encapsulation strategy we have prepared MGL
      nanoporous wet silica gels. Immobilized MGL gels were characterized with regards
      to activity, stability, absorption, circular dichroism and fluorescence
      properties and compared with soluble MGL. We found that MGL gels exhibit (i)
      spectroscopic properties very similar to MGL in solution, (ii) a higher stability
      with respect to the soluble enzyme and (iii) catalytic activity six-fold lower
      than in solution. These findings prove that MGL encapsulation is a suitable
      strategy for therapeutic applications.

PMID- 29448749
TI  - Nanosized-Particle Dispersion-Strengthened Al Matrix Composites Fabricated by the
      Double Mechanical Alloying Process.
AB  - The objective of this study was to fabricate an Al metal matrix composite
      strengthened by nanosized Al3Ti particles via double mechanical alloying process.
      Several Al-xTi alloys were fabricated, including Al-12%Ti, Al-15%Ti, and Al-12%Ti
      1%Y2O3. The lattice parameter of as-milled state was calculated to be 4.0485 A;
      after a milling time of 540 min, it was 4.0401 A. This decrease was induced by Ti
      solutionizing into the Al matrix. The equivalent size of a coarse Al3Ti particle
      was 200-500 nm after the heat treatment; however, the particles were uniformly
      distributed and were refined through the MA2 process. The particle size of a
      Al3Ti phase was 30 nm or less, and the particles were uniformly distributed.
      These particles remained in a fine state in the matrix without growth and
      coarsening, even after the hot extrusion process. The microstructure of hot
      extruded alloys consisted of a uniform distribution of Al3Ti particles and other
      dispersoids in the Al matrix.

PMID- 29448750
TI  - Evaluation of Acid Etching on Surface Characteristics, Strength and Biological
      Response of Glass-Infiltrated Zirconia.
AB  - This study evaluated the effect of acid etching on surface characteristics,
      flexural strength and osteoblast cell response of glass-infiltrated zirconia.
      Zirconia specimens were divided into six groups: untreated zirconia (Z); glass
      infiltrated zirconia (ZG); glass-infiltrated and sandblasted zirconia (ZGS);
      glass-infiltrated, sandblasted and 5 min acid-etched zirconia (ZGS-E5);
      glassinfiltrated, sandblasted and 15 min acid-etched zirconia (ZGS-E15); glass
      infiltrated, sandblasted and 25 min acid-etched zirconia (ZGS-E25). Surface
      roughness, biaxial flexural strength and MC3T3-E1 cell proliferation were
      evaluated. When increasing etching time, surface roughness significantly
      increased while flexural strength decreased. Cell proliferation rate at day 3 on
      group ZGS-E15 and ZGS-E25 was significantly higher than that of other groups.
      Surface roughness and flexural strength of glass-infiltrated zirconia can be
      controlled by adjusting etching time. Rough surface made by acid etching
      following glass infiltration significantly enhanced osteoblast cell response.
      Glass infiltration improved strength of zirconia but severe acid etching slightly
      reduced strength of zirconia.

PMID- 29448751
TI  - Effect of Zn on Pore Characteristics in Lotus-Type Porous Cu.
AB  - The effect of Zn on pore characteristics in lotus-type porous Cu alloy was
      investigated. The lotustype porous Cu-Zn alloys were fabricated with Zn content
      from 0.01 to 0.1 at% by the centrifugal casting method. The results demonstrated
      that the porosity was rarely affected by Zn content. However, the average pore
      diameter and pore number density of the lotus type porous Cu-Zn alloys were
      significantly affected by the Zn content. The average pore diameter decreased as
      the Zn content increased up to 0.01 at%, and then increased as the Zn content
      increased up to 0.1 at%. In contrast, the variations in the pore number density
      of the lotus-type porous Cu-Zn alloys showed the reversed tendency with respect
      to that of the average pore diameter. The increase in heterogeneous nucleation
      sites for pores attributed to the decreased average pore diameter and the
      increased pore number density.

PMID- 29448752
TI  - Effect of Deposition Height on Nanostructure of Tungsten Oxide Thin Films in
      Flame Vapor Deposition Process.
AB  - Vertically aligned nanostructured tungsten oxide thin films have been found
      useful in many applications due to its intrinsic photonic and electronic
      properties. In this study, we directly prepared vertically aligned nanostructures
      including nanowires and nanotubes grown directly on FTO-coated glass by a newly
      designed flame vapor deposition system. The deposition height was found to be an
      important parameter for the development of thin film morphology. The evolution of
      nanowires and nanotubes with time was investigated. Based on our observation, the
      feasible growth mechanisms of distinct nanostructures were proposed.

PMID- 29448753
TI  - Tailored Pt/TiO2 Photocatalyst with Controllable Phase Prepared via a Modified
      Sol-Gel Process for Dye Degradation.
AB  - Pt/TiO2 photocatalysts with controllable phase were successfully prepared by
      controlling the hydrolysis pH values during the sol-gel process followed by Pt
      photodeposition. The effect of different phases of TiO2 coated with Pt on the
      catalytic properties and the photocatalytic activities were also investigated.
      The characterization results of the synthesis of TiO2 under neutral/alkaline and
      acidic conditions during the hydrolysis step revealed the facile formation of the
      anatase phase and the brookite/rutile phase, respectively. Pt/TiO2 photocatalysts
      prepared at hydrolysis pH values of 2, 7, and 10 had different TiO2 phase
      compositions, but the main crystalline sizes of the photocatalysts were all close
      to 6 nm. The Pt/TiO2 particles prepared at various hydrolysis pH values were all
      spheroidal. The PL results indicated that the anatase/rutile junction of a
      Pt/TiO2 sample had a lower recombination rate than did the anatase phase of
      Pt/TiO2 owing to the longer recombination pathway. However, the anatase phase of
      Pt/TiO2 exhibited better degradation ability than the anatase/rutile junction of
      Pt/TiO2, and the degradation rate decreased with a decrease in the anatase
      composition of TiO2, indicating that anatase composition in the Pt/TiO2 system
      played an important role of enhancing the photocatalytic degradation of Acid Red
      1 dye.

PMID- 29448754
TI  - Adsorption Behavior of Recyclable Magnetites with N-Components for Adsorption of
      Copper Ion.
AB  - Recyclable magnetites with thioureido group (poly-allyl-thiourea/oleic
      acid/magnetite, PAT-adsorbent) and amine functional group (ethylenediamine/methyl
      methacrylate/oleic acid/magnetite, EDA-adsorbent) were synthesized by modifying
      magnetite with oleic acid, methyl methacrylate, allyl thiourea and
      ethylenediamine. PAT-adsorbent and EDA-adsorbent were used and compared for
      adsorption of copper ions in a batch system due to the existence of amino group (
      NH2) both on thioureido group and amine functional group. The kinetics of both
      PAT-adsorbent and EDA-adsorbent were evaluated utilizing pseudo-first-order and
      pseudo-second-order kinetic models. The equilibrium data was analyzed and
      compared using the Langmuir and Freundlich isotherm models. The maximum
      adsorption capacity (Qm) of PAT-adsorbent (19.126 mg g-1) was higher than that of
      EDA-adsorbent (7.096 mg g-1). As compared to EDA-adsorbent the magnetic adsorbent
      (PAT-adsorbent) with good desorption performance (>85% desorption efficiency) and
      easily reuse (>85% recovery by magnetic force) was the important factors for its
      potential practical application.

PMID- 29448755
TI  - Removal of Humic Acid in Water Using Novel Nanomaterials.
AB  - The present study investigates the effectiveness of the photocatalytic
      degradation of humic acid (HA) in aqueous suspensions. Initial batch scale
      experiments and tests performed using the Continuous Flow Photoreactor have
      enabled the close inspection of the performance of the photocatalysts nano TiO2,
      and nano ZnO dispersions. These photocatalysts were used in aqueous dispersions
      employing medium-pressure mercury-vapour lamps emitting UV-A (lambda = 400 nm)
      and UV-C (lambda = 250 nm). Moreover, glass microfibre filters were embedded and
      coated with Laponite RD (synthetic polycrystalline swelling clay) in order to
      produce catalytic films to be used in small scale experiments to remove HA
      through filtration. The findings of this study shows that the HA adsorb highly
      onto the ZnO and TiO2 surface thus initiating photodegradation, the effectiveness
      of which steadily increases with irradiation time along with an increase in the
      biodegradability of HA.

PMID- 29448756
TI  - Ductile Crack Initiation Criterion with Mismatched Weld Joints Under Dynamic
      Loading Conditions.
AB  - Brittle failure of high toughness steel structures tends to occur after ductile
      crack initiation/propagation. Damages to steel structures were reported in the
      Hanshin Great Earthquake. Several brittle failures were observed in beam-to
      column connection zones with geometrical discontinuity. It is widely known that
      triaxial stresses accelerate the ductile fracture of steels. The study examined
      the effects of geometrical heterogeneity and strength mismatches (both of which
      elevate plastic constraints due to heterogeneous plastic straining) and loading
      rate on critical conditions initiating ductile fracture. This involved applying
      the two-parameter criterion (involving equivalent plastic strain and stress
      triaxiality) to estimate ductile cracking for strength mismatched specimens under
      static and dynamic tensile loading conditions. Ductile crack initiation testing
      was conducted under static and dynamic loading conditions using circumferentially
      notched specimens (Charpy type) with/without strength mismatches. The results
      indicated that the condition for ductile crack initiation using the two parameter
      criterion was a transferable criterion to evaluate ductile crack initiation
      independent of the existence of strength mismatches and loading rates.

PMID- 29448757
TI  - Effect of Inductively Coupled Plasma on the Properties of Nanocrystalline
      Vanadium Nitride Films for Corrosion Resistant Surface.
AB  - Single-phase cubic (FCC) vanadium nitride (VN) coatings with different
      preferential orientations and residual stresses were obtained as a function of
      ICP power. Microstructural, crystallographic and mechanical characterizations
      were performed by FE-SEM, AFM, XRD and nanoindentation. The results show that ICP
      has significant effects on coating's microstructure, structural and mechanical
      properties of VN coatings. With an increase in ICP power, coating microstructure
      evolved from a porous columnar structure to a highly dense one. Single-phase
      cubic (FCC) VN coatings with different preferential orientations and residual
      stresses were obtained as a function of ICP power. Average crystal grain sizes of
      single phase cubic VN coatings were decreased from 10.1 nm to 4.0 nm with an
      increase in ICP power. Maximum hardness of 28.2 GPa was obtained for the coatings
      deposited at ICP power of 200 W.

PMID- 29448758
TI  - Pore Characteristics of Lotus-Type Porous Cu-Fe and Cu-Cr Alloys Fabricated by
      Unidirectional Solidification.
AB  - Lotus-type porous Cu-Fe and Cu-Cr with long cylindrical pores was fabricated by
      centrifugal casting under hydrogen atmosphere and the effect of alloying elements
      on pore characteristics of lotus-type porous Cu was investigated. For the lotus
      type porous Cu-Fe alloy, the porosity slightly decreased and the average pore
      diameter slightly increased with increasing Fe content. For the lotus-type porous
      Cu-Cr alloy, the porosity sharply decreased and the average pore diameter
      drastically increased with an increase in the Cr content. From these results, it
      was found that the pore evolution and growth are affected by alloying element and
      this leads to the change in the pore characteristics of lotus-type porous Cu-Fe
      and Cu-Cr alloys.

PMID- 29448759
TI  - Multi c-BN Coatings by r.f Diode Sputtering and Investigation of Wear Behavior.
AB  - Cubic boron nitride (c-BN) films on tool substrates are tendency to delaminate.
      Therefore, many research groups have studied improvement of c-BN synthesis method
      and deposition processes due to many potential applications. In this paper, we
      show that the adhesion property of c-BN layer system can be improved by deposing
      multi c-BN layers. The multi c-BN layers were deposited by r.f (13.56 MHz) diode
      sputtering apparatus on cemented carbide tool substrates with a TiAlN adhesion
      layer. For industrial applications, we performed turning and milling experiments
      under dry and high speed cutting conditions. In this multi c-BN layer system, the
      lifetime of the tool is affected by the physical properties of the substrate and
      coated layers such as substrate grain size, thickness of the TiAlN and first c-BN
      layer and the total number of c-BN layers in this system. Mostly, fine grain size
      substrates showed longer lifetimes of over 4 times than raw one. In the turning
      performance, mono TiAlN layer systems were about two times lower lifetime than
      mono and multi c-BN layer system, moreover, we could be improved adhesion
      property for milling performance on tool substrates with binary multi c-BN layer
      systems under dry and high speed cutting conditions. The new application results
      of the multi c-BN layer system confirm that the high potential of c-BN coatings
      on cutting tools.

PMID- 29448760
TI  - Identification of New Compounds from Sage Flowers (Salvia officinalis L.) as
      Markers for Quality Control and the Influence of the Manufacturing Technology on
      the Chemical Composition and Antibacterial Activity of Sage Flower Extracts.
AB  - Parts of Salvia species such as its flowers and leaves are currently used as a
      culinary herb and for some medicinal applications. To distinguish the different
      sage extracts it is necessary to analyze their individual chemical compositions.
      Their characteristic compounds might be established as markers to differentiate
      between sage flowers and leaf extracts or to determine the manufacturing
      technology and storage conditions. Tri-p-coumaroylspermidine can be detected only
      in flowers and has been described here for Salvia and Lavandula species for the
      first time. Markers for oxidation processes are the novel compounds salviquinone
      A and B, which were generated from carnosol by exposure to oxygen. Caffeic acid
      ethyl ester was established as an indirect marker for the usage of ethanol as
      extraction solvent. The compounds were identified by LC-QTOF-HRESIMS, LC-MS, NMR,
      IR, and single-crystal X-ray diffraction after isolation by semipreparative HPLC.
      Furthermore, sage flower resin showed interesting antibacterial in vitro
      activities against Gram-positive and Gram-negative bacteria.

PMID- 29448761
TI  - Spotlight: A Conversation with Laura Kiessling and Jennifer Doudna.
AB  - ACS Chemical Biology recorded a special podcast, in which Editor-in-Chief Laura
      Kiessling (Massachusetts Institute of Technology) interviews CRISPR investigator
      and former Associate Editor Jennifer Doudna (University of California, Berkeley).
      Listen to the podcast here . A transcript of the interview, which has been
      lightly edited, is published here as part of our Special Issue on the Chemical
      Biology of CRISPR.

PMID- 29448763
TI  - Special Issue on the Chemical Biology of CRISPR.

PMID- 29448764
TI  - Frontiers in CRISPR.
AB  - CRISPR-based approaches to genetic engineering are progressing at a rapid pace
      and present exciting new avenues for science, medicine, and technology. Many of
      the most cutting-edge advances in genome engineering are encompassed in the
      Research Articles, Reviews, and Perspectives in this special issue, often with an
      eye toward future directions for the field. Yet, many questions remain at this
      new frontier. We asked over 100 CRISPR researchers, including our contributing
      authors, for their perspectives on some of the most pressing questions
      surrounding the future of genome engineering and the CRISPR-Cas platform, the
      challenges that lie ahead, and opportunities for chemists and chemical biologists
      to drive creative molecular solutions.

PMID- 29448766
TI  - Escape rate for nonequilibrium processes dominated by strong non-detailed balance
      force.
AB  - Quantifying the escape rate from a meta-stable state is essential to understand a
      wide range of dynamical processes. Kramers' classical rate formula is the product
      of an exponential function of the potential barrier height and a pre-factor
      related to the friction coefficient. Although many applications of the rate
      formula focused on the exponential term, the prefactor can have a significant
      effect on the escape rate in certain parameter regions, such as the overdamped
      limit and the underdamped limit. There have been continuous interests to
      understand the effect of non-detailed balance on the escape rate; however, how
      the prefactor behaves under strong non-detailed balance force remains elusive. In
      this work, we find that the escape rate formula has a vanishing prefactor with
      decreasing friction strength under the strong non-detailed balance limit. We both
      obtain analytical solutions in specific examples and provide a derivation for
      more general cases. We further verify the result by simulations and propose a
      testable experimental system of a charged Brownian particle in electromagnetic
      field. Our study demonstrates that a special care is required to estimate the
      effect of prefactor on the escape rate when non-detailed balance force dominates.

PMID- 29448767
TI  - Crystal nucleation in sedimenting colloidal suspensions.
AB  - Homogeneous crystal nucleation from a metastable hard-sphere colloidal liquid has
      been extensively studied in simulations and experiments. A 12 order of magnitude
      difference between simulated and experimental nucleation rates is observed, the
      origin of which remains a puzzle. Here, we experimentally study crystal
      nucleation at the single particle level in suspensions of hard-sphere-like
      colloids under the influence of sedimentation. We find that sedimentation
      significantly enhances the nucleation rate, but contrary to what was previously
      thought, this is not due to simple density fluctuations, as the nucleation
      barriers become independent of the local density in a sedimentating fluid.
      Instead, we find an enhancement of the local dynamics, which suggests that local
      convective cells are responsible for shear-enhanced crystallization at low volume
      fractions.

PMID- 29448768
TI  - Mobility and settling rate of agglomerates of polydisperse nanoparticles.
AB  - Agglomerate settling impacts nanotoxicology and nanomedicine as well as the
      stability of engineered nanofluids. Here, the mobility of nanostructured fractal
      like SiO2 agglomerates in water is investigated and their settling rate in
      infinitely dilute suspensions is calculated by a Brownian dynamics algorithm
      tracking the agglomerate translational and rotational motion. The corresponding
      friction matrices are obtained using the HYDRO++ algorithm [J. G. de la Torre, G.
      del Rio Echenique, and A. Ortega, J. Phys. Chem. B 111, 955 (2007)] from the
      Kirkwood-Riseman theory accounting for hydrodynamic interactions of primary
      particles (PPs) through the Rotne-Prager-Yamakawa tensor, properly modified for
      polydisperse PPs. Agglomerates are generated by an event-driven method and have
      constant mass fractal dimension but varying PP size distribution, mass, and
      relative shape anisotropy. The calculated diffusion coefficient from HYDRO++ is
      used to obtain the agglomerate mobility diameter dm and is compared with that
      from scaling laws for fractal-like agglomerates. The ratio dm/dg of the mobility
      diameter to the gyration diameter of the agglomerate decreases with increasing
      relative shape anisotropy. For constant dm and mean dp, the agglomerate settling
      rate, us, increases with increasing PP geometric standard deviation sigmap,g
      (polydispersity). A linear relationship between us and agglomerate mass to dm
      ratio, m/dm, is revealed and attributed to the fast Brownian rotation of such
      small and light nanoparticle agglomerates. An analytical expression for the us of
      agglomerates consisting of polydisperse PPs is then derived, us=1
      rhofrhopg3piMUmdm (rhof is the density of the fluid, rhop is the density of PPs,
      MU is the viscosity of the fluid, and g is the acceleration of gravity), valid
      for agglomerates for which the characteristic rotational time is considerably
      shorter than their settling time. Our calculations demonstrate that the commonly
      made assumption of monodisperse PPs underestimates us by a fraction depending on
      sigmap,g and agglomerate mass mobility exponent. Simulations are in excellent
      agreement with deposition rate measurements of fumed SiO2 agglomerates in water.

PMID- 29448769
TI  - Nanobubbles in confined solution: Generation, contact angle, and stability.
AB  - The formation of gas bubbles presents a frequent challenge to microfluidic
      operations, for which fluids are geometrically confined to a microscale space.
      Here, to understand the mechanism of nucleating gas bubbles in microfluidic
      devices, we investigate the formation and stability of nanobubbles in confined
      solutions. Our molecular dynamics simulations show that while pinning of the
      contact line is a prerequisite for the stability of surface nanobubbles in open
      systems that can exchange gas with surrounding environment, in confined
      solutions, stable nanobubbles can exist even without pinning. In supersaturated
      condition, stable bubbles can be found in confined solutions with acute or obtuse
      contact angle, depending on the substrate hydrophobicity. We also demonstrate
      that when open to the bulk solution, the stable nanobubbles in closed systems
      would become unstable unless both supersaturation and pinning of the contact line
      are satisfied. Our results not only shed light on the design of novel
      heterogeneous surfaces for generating nanobubbles in confined space with
      controllable shape and stability but also address the crucial effect of gas
      exchange with the surroundings in determining the stability of nanobubbles.

PMID- 29448770
TI  - Product interactions and feedback in diffusion-controlled reactions.
AB  - Steric or attractive interactions among reactants or between reactants and inert
      crowders can substantially influence the total rate of a diffusion-influenced
      reaction in the liquid phase. However, the role of the product species, which has
      typically different physical properties than the reactant species, has been
      disregarded so far. Here we study the effects of reactant-product and product
      product interactions as well as asymmetric diffusion properties on the rate of
      diffusion-controlled reactions in the classical Smoluchowski-setup for chemical
      transformations at a perfect catalytic sphere. For this, we solve the diffusion
      equation with appropriate boundary conditions coupled by a mean-field approach on
      the second virial level to account for the particle interactions. We find that
      all particle spatial distributions and the total rate can change significantly,
      depending on the diffusion and interaction properties of the accumulated
      products. Complex competing and self-regulating (homeostatic) or self-amplifying
      effects are observed for the system, leading to both decrease and increase in the
      rates, as the presence of interacting products feeds back to the reactant flux
      and thus the rate with which the products are generated.

PMID- 29448771
TI  - Dark states and delocalization: Competing effects of quantum coherence on the
      efficiency of light harvesting systems.
AB  - Natural light harvesting systems exploit electronic coupling of identical
      chromophores to generate efficient and robust excitation transfer and conversion.
      Dark states created by strong coupling between chromophores in the antenna
      structure can significantly reduce radiative recombination and enhance energy
      conversion efficiency. Increasing the number of the chromophores increases the
      number of dark states and the associated enhanced energy conversion efficiency
      yet also delocalizes excitations away from the trapping center and reduces the
      energy conversion rate. Therefore, a competition between dark state protection
      and delocalization must be considered when designing the optimal size of a light
      harvesting system. In this study, we explore the two competing mechanisms in a
      chain-structured antenna and show that dark state protection is the dominant
      mechanism, with an intriguing dependence on the parity of the number of
      chromophores. This dependence is linked to the exciton distribution among
      eigenstates, which is strongly affected by the coupling strength between
      chromophores and the temperature. Combining these findings, we propose that
      increasing the coupling strength between the chromophores can significantly
      increase the power output of the light harvesting system.

PMID- 29448772
TI  - Publisher's Note: "Non-adiabatic quantum reactive scattering in hyperspherical
      coordinates" [J. Chem. Phys. 148, 044116 (2018)].

PMID- 29448773
TI  - A theoretical and experimental benchmark study of core-excited states in
      nitrogen.
AB  - The high resolution near edge X-ray absorption fine structure spectrum of
      nitrogen displays the vibrational structure of the core-excited states. This
      makes nitrogen well suited for assessing the accuracy of different electronic
      structure methods for core excitations. We report high resolution experimental
      measurements performed at the SOLEIL synchrotron facility. These are compared
      with theoretical spectra calculated using coupled cluster theory and algebraic
      diagrammatic construction theory. The coupled cluster singles and doubles with
      perturbative triples model known as CC3 is shown to accurately reproduce the
      experimental excitation energies as well as the spacing of the vibrational
      transitions. The computational results are also shown to be systematically
      improved within the coupled cluster hierarchy, with the coupled cluster singles,
      doubles, triples, and quadruples method faithfully reproducing the experimental
      vibrational structure.

PMID- 29448774
TI  - Incorporating extrinsic noise into the stochastic simulation of biochemical
      reactions: A comparison of approaches.
AB  - The stochastic simulation algorithm (SSA) has been widely used for simulating
      biochemical reaction networks. SSA is able to capture the inherently intrinsic
      noise of the biological system, which is due to the discreteness of species
      population and to the randomness of their reciprocal interactions. However, SSA
      does not consider other sources of heterogeneity in biochemical reaction systems,
      which are referred to as extrinsic noise. Here, we extend two simulation
      approaches, namely, the integration-based method and the rejection-based method,
      to take extrinsic noise into account by allowing the reaction propensities to
      vary in time and state dependent manner. For both methods, new efficient
      implementations are introduced and their efficiency and applicability to
      biological models are investigated. Our numerical results suggest that the
      rejection-based method performs better than the integration-based method when the
      extrinsic noise is considered.

PMID- 29448775
TI  - Molecular simulation of steady-state evaporation and condensation in the presence
      of a non-condensable gas.
AB  - Using molecular dynamics simulations, we study evaporation and condensation of
      fluid Ar in the presence of a non-condensable Ne gas in a nanochannel. The
      evaporation and condensation are driven by the temperature difference, DeltaTL,
      between the evaporating and condensing liquid surfaces. The steady-state
      evaporation and condensation fluxes (JMD) are also affected by the Ne
      concentration, rhoNe, and the nanochannel length. We find that across a wide
      range of DeltaTL and rhoNe, JMD is in good agreement with the prediction from
      Stefan's law and from Schrage relationships. Furthermore, for DeltaTL less than
      ~20% of the absolute average temperature, we find that both steady-state heat and
      mass fluxes are proportional to DeltaTL. This allows us to determine the
      interfacial resistance to the heat and mass transfer and compare it with the
      corresponding resistances in the gas phase. In this context, we derive an
      analytical expression for the effective thermal conductivity of the gas region in
      the nanochannel and the mass transport interfacial resistance equivalent length,
      i.e., the length of the nanochannel for which the resistance to the mass flow is
      the same as the interfacial resistance to the mass flow.

PMID- 29448776
TI  - Employing general fit-bases for construction of potential energy surfaces with an
      adaptive density-guided approach.
AB  - We present an approach to treat sets of general fit-basis functions in a single
      uniform framework, where the functional form is supplied on input, i.e., the use
      of different functions does not require new code to be written. The fit-basis
      functions can be used to carry out linear fits to the grid of single points,
      which are generated with an adaptive density-guided approach (ADGA). A non-linear
      conjugate gradient method is used to optimize non-linear parameters if such are
      present in the fit-basis functions. This means that a set of fit-basis functions
      with the same inherent shape as the potential cuts can be requested and no other
      choices with regards to the fit-basis functions need to be taken. The general fit
      basis framework is explored in relation to anharmonic potentials for model
      systems, diatomic molecules, water, and imidazole. The behaviour and performance
      of Morse and double-well fit-basis functions are compared to that of polynomial
      fit-basis functions for unsymmetrical single-minimum and symmetrical double-well
      potentials. Furthermore, calculations for water and imidazole were carried out
      using both normal coordinates and hybrid optimized and localized coordinates
      (HOLCs). Our results suggest that choosing a suitable set of fit-basis functions
      can improve the stability of the fitting routine and the overall efficiency of
      potential construction by lowering the number of single point calculations
      required for the ADGA. It is possible to reduce the number of terms in the
      potential by choosing the Morse and double-well fit-basis functions. These
      effects are substantial for normal coordinates but become even more pronounced if
      HOLCs are used.

PMID- 29448777
TI  - Laplace transformed MP2 for three dimensional periodic materials using stochastic
      orbitals in the plane wave basis and correlated sampling.
AB  - We present an implementation and analysis of a stochastic high performance
      algorithm to calculate the correlation energy of three-dimensional periodic
      systems in second-order Moller-Plesset perturbation theory (MP2). In particular
      we measure the scaling behavior of the sample variance and probe whether this
      stochastic approach is competitive if accuracies well below 1 meV per valence
      orbital are required, as it is necessary for calculations of adsorption, binding,
      or surface energies. The algorithm is based on the Laplace transformed MP2
      (LTMP2) formulation in the plane wave basis. The time-dependent Hartree-Fock
      orbitals, appearing in the LTMP2 formulation, are stochastically rotated in the
      occupied and unoccupied Hilbert space. This avoids a full summation over all
      combinations of occupied and unoccupied orbitals, as inspired by the work of
      Neuhauser, Rabani, and Baer [J. Chem. Theory Comput. 9, 24 (2013)]. Additionally,
      correlated sampling is introduced, accelerating the statistical convergence
      significantly.

PMID- 29448778
TI  - Remarks on the chemical Fokker-Planck and Langevin equations: Nonphysical
      currents at equilibrium.
AB  - The chemical Langevin equation and the associated chemical Fokker-Planck equation
      are well-known continuous approximations of the discrete stochastic evolution of
      reaction networks. In this work, we show that these approximations suffer from a
      physical inconsistency, namely, the presence of nonphysical probability currents
      at the thermal equilibrium even for closed and fully detailed-balanced kinetic
      schemes. An illustration is given for a model case.

PMID- 29448779
TI  - Flow of quasi-two dimensional water in graphene channels.
AB  - When liquids confined in slit channels approach a monolayer, they become two
      dimensional (2D) fluids. Using molecular dynamics simulations, we study the flow
      of quasi-2D water confined in slit channels featuring pristine graphene walls and
      graphene walls with hydroxyl groups. We focus on to what extent the flow of quasi
      2D water can be described using classical hydrodynamics and what are the
      effective transport properties of the water and the channel. First, the in-plane
      shearing of quasi-2D water confined between pristine graphene can be described
      using the classical hydrodynamic equation, and the viscosity of the water is ~50%
      higher than that of the bulk water in the channel studied here. Second, the flow
      of quasi-2D water around a single hydroxyl group is perturbed at a position of
      tens of cluster radius from its center, as expected for low Reynolds number
      flows. Even though water is not pinned at the edge of the hydroxyl group, the
      hydroxyl group screens the flow greatly, with a single, isolated hydroxyl group
      rendering drag similar to ~90 nm2 pristine graphene walls. Finally, the flow of
      quasi-2D water through graphene channels featuring randomly distributed hydroxyl
      groups resembles the fluid flow through porous media. The effective friction
      factor of the channel increases linearly with the hydroxyl groups' area density
      up to 0.5 nm-2 but increases nonlinearly at higher densities. The effective
      friction factor of the channel can be fitted to a modified Carman equation at
      least up to a hydroxyl area density of 2.0 nm-2. These findings help understand
      the liquid transport in 2D material-based nanochannels for applications including
      desalination.

PMID- 29448781
TI  - Anion photoelectron spectroscopy of deprotonated indole and indoline.
AB  - Anion photoelectron spectra of deprotonated indole have been obtained utilizing
      several photon energies. The slow electron velocity-map imaging spectrum of
      indolide allows for the determination of the electron affinity (EA) of indolyl,
      2.4315 +/- 0.0017 eV. The equilibrium geometry of indolide was shown to minimally
      distort upon photodetachment with only ring distortion vibrational modes of A'
      symmetry becoming significantly excited. Photoelectron spectra of indolide
      accessing the electronic ground state of indolyl displayed a photon energy
      dependence due to electron autodetachment. Combining the EA of indolyl with the
      previous work studying the dissociation energy of H-indolyl allows for a new
      independent measure of DeltaacidH0KoN-Hindole <= 348.7 kcal/mol, which improves
      the previous measurement of the gas phase acidity. The anion photoelectron
      spectrum of deprotonated indoline consisted of a featureless broad band extending
      from ~1.3 eV to 1.7 eV electron binding energy. The congested nature of the
      spectrum is likely due to the presence of multiple isomers of deprotonated
      indoline, including ring-opened structures.

PMID- 29448780
TI  - Semiexperimental and mass-dependent structures by the mixed regression method:
      Accurate equilibrium structure and failure of the Kraitchman method for
      ethynylcyclohexane.
AB  - The mixed regression method for determination of molecular structures is reviewed
      and applied to the investigation of ethynylcyclohexane, using both
      semiexperimental and mass-dependent methods. This methodology provides an
      efficient and computationally affordable route to obtain accurate molecular
      reference data, preventing ill-conditioning in the structural least-squares
      determinations from experimental rotational constants. New supersonic-jet
      microwave measurements are reported to obtain inertial data for the axial and
      equatorial species of ethynylcyclohexane, together with all 13C isotopologues of
      the equatorial form. The semiexperimental equilibrium (reSE) and mass-dependent
      (rm(2)) structures of the molecule are compared with high-level ab initio
      optimizations, showing that both methods deliver compatible structures with
      accuracies of about 0.002 A for bond lengths and 0.2 degrees  for bond angles. We
      confirm that dependable predicates can be obtained for a large variety of bonds.
      Finally, we verify that the substitution method completely fails to determine a
      reliable structure for the title compound.

PMID- 29448782
TI  - Pressure control in interfacial systems: Atomistic simulations of vapor
      nucleation.
AB  - A large number of phenomena of scientific and technological interest involve
      multiple phases and occur at constant pressure of one of the two phases, e.g.,
      the liquid phase in vapor nucleation. It is therefore of great interest to be
      able to reproduce such conditions in atomistic simulations. Here we study how
      popular barostats, originally devised for homogeneous systems, behave when
      applied straightforwardly to heterogeneous systems. We focus on vapor nucleation
      from a super-heated Lennard-Jones liquid, studied via hybrid restrained Monte
      Carlo simulations. The results show a departure from the trends predicted for the
      case of constant liquid pressure, i.e., from the conditions of classical
      nucleation theory. Artifacts deriving from standard (global) barostats are shown
      to depend on the size of the simulation box. In particular, for Lennard-Jones
      liquid systems of 7000 and 13 500 atoms, at conditions typically found in the
      literature, we have estimated an error of 10-15 kBT on the free-energy barrier,
      corresponding to an error of 104-106 s-1sigma-3 on the nucleation rate. A
      mechanical (local) barostat is proposed which heals the artifacts for the
      considered case of vapor nucleation.

PMID- 29448783
TI  - Molecular dynamics simulation of ion mobility in gases.
AB  - A force field molecular dynamics method is developed to directly simulate ion
      drift in buffer gases driven by an electric field. The ion mobility and collision
      cross sections (CCSs) with relevance to ion mobility spectrometry can be obtained
      from the simulated drift velocity in high-density buffer gases (pressure ~50
      bars) and high electric fields (~107 V/m). Compared to trajectory methods, the
      advantage of the molecular dynamics method is that it can simultaneously sample
      the internal dynamic motions of the ion and the ion-gas collisions. For ions with
      less than 100 atoms, the simulated collision cross section values can be
      converged to within +/-1%-2% by running a 100 ns simulation for 5-19 h using one
      computer core. By using a set of element-based Lennard-Jones parameters that are
      not tuned for different atomic types in different molecules, the simulated
      collision cross sections for 15 small molecular ions (number of atoms ranging
      from 17 to 85, mass ranging from 74.1 to 609.4 g/mol) are consistent with
      experimental values: the mean unsigned error is 2.6 A2 for He buffer gas and 4.4
      A2 for N2 buffer gas. The sensitivity of the simulated CCS values to random
      diffusion, drift velocity, electric field strength, temperature, and buffer gas
      density is examined.

PMID- 29448784
TI  - Dirac cone in two dimensional bilayer graphene by intercalation with V, Nb, and
      Ta transition metals.
AB  - Bilayer graphene (BLG) is a semiconductor whose band gap and properties can be
      tuned by various methods such as doping or applying gate voltage. Here, we show
      how to tune electronic properties of BLG by intercalation of transition metal
      (TM) atoms between two monolayer graphene (MLG) using a novel dispersion
      corrected first-principle density functional theory (DFT) approach. We
      intercalated V, Nb, and Ta atoms between two MLG. We found that the symmetry, the
      spin, and the concentration of TM atoms in BLG-intercalated materials are the
      important parameters to control and to obtain a Dirac cone in their band
      structures. Our study reveals that the BLG intercalated with one vanadium (V)
      atom, BLG-1V, has a Dirac cone at the K-point. In all the cases, the present DFT
      calculations show that the 2pz sub-shells of C atoms in graphene and the 3dyz sub
      shells of the TM atoms provide the electron density near the Fermi energy level
      (EF) which controls the material properties. Thus, we show that out-of-plane
      atoms can influence in-plane electronic densities in BLG and enumerate the
      conditions necessary to control the Dirac point. This study offers insight into
      the physical properties of 2D BLG intercalated materials and presents a new
      strategy for controlling the electronic properties of BLG through TM
      intercalation by varying the concentration and spin arrangement of the metals
      resulting in various conducting properties, which include: metal, semi-metal and
      semiconducting states.

PMID- 29448785
TI  - MC-PDFT can calculate singlet-triplet splittings of organic diradicals.
AB  - The singlet-triplet splittings of a set of diradical organic molecules are
      calculated using multiconfiguration pair-density functional theory (MC-PDFT), and
      the results are compared with those obtained by Kohn-Sham density functional
      theory (KS-DFT) and complete active space second-order perturbation theory
      (CASPT2) calculations. We found that MC-PDFT, even with small and systematically
      defined active spaces, is competitive in accuracy with CASPT2, and it yields
      results with greater accuracy and precision than Kohn-Sham DFT with the parent
      functional. MC-PDFT also avoids the challenges associated with spin contamination
      in KS-DFT. It is also shown that MC-PDFT is much less computationally expensive
      than CASPT2 when applied to larger active spaces, and this illustrates the
      promise of this method for larger diradical organic systems.

PMID- 29448786
TI  - Structural relaxation and highly viscous flow.
AB  - The highly viscous flow is due to thermally activated Eshelby transitions which
      transform a region of the undercooled liquid to a different structure with a
      different elastic misfit to the viscoelastic surroundings. A self-consistent
      determination of the viscosity in this picture explains why the average
      structural relaxation time is a factor of eight longer than the Maxwell time. The
      physical reason for the short Maxwell time is the very large contribution of
      strongly strained inherent states to the fluidity (the inverse viscosity). At the
      Maxwell time, the viscous no-return processes coexist with the back-and-forth
      jumping retardation processes.

PMID- 29448787
TI  - Adaptive frozen orbital treatment for the fragment molecular orbital method
      combined with density-functional tight-binding.
AB  - The exactly analytic gradient is derived and implemented for the fragment
      molecular orbital (FMO) method combined with density-functional tight-binding
      (DFTB) using adaptive frozen orbitals. The response contributions which arise
      from freezing detached molecular orbitals on the border between fragments are
      computed by solving Z-vector equations. The accuracy of the energy, its gradient,
      and optimized structures is verified on a set of representative inorganic
      materials and polypeptides. FMO-DFTB is applied to optimize the structure of a
      silicon nano-wire, and the results are compared to those of density functional
      theory and experiment. FMO accelerates the DFTB calculation of a boron nitride
      nano-ring with 7872 atoms by a factor of 406. Molecular dynamics simulations
      using FMO-DFTB applied to a 10.7 MUm chain of boron nitride nano-rings,
      consisting of about 1.2 * 106 atoms, reveal the rippling and twisting of nano
      rings at room temperature.

PMID- 29448788
TI  - Erratum: "Two-structure thermodynamics for the TIP4P/2005 model of water covering
      supercooled and deeply stretched regions" [J. Chem. Phys. 146, 034502 (2017)].

PMID- 29448789
TI  - Three-body dissociation of OCS3+: Separating sequential and concerted pathways.
AB  - Events from the sequential and concerted modes of the fragmentation of OCS3+ that
      result in coincident detection of fragments C+, O+, and S+ have been separated
      using a newly proposed representation. An ion beam of 1.8 MeV Xe9+ is used to
      make the triply charged molecular ion, with the fragments being detected by a
      recoil ion momentum spectrometer. By separating events belonging exclusively to
      the sequential mode of breakup, the electronic states of the intermediate
      molecular ion (CO2+ or CS2+) involved are determined, and from the kinetic energy
      release spectra, it is shown that the low lying excited states of the parent
      OCS3+ are responsible for this mechanism. An estimate of branching ratios of
      events coming from sequential versus concerted mode is presented.

PMID- 29448790
TI  - Benchmarking several van der Waals dispersion approaches for the description of
      intermolecular interactions.
AB  - Seven methods, including three van der Waals density functionals (vdW-DFs) and
      four different variants of the Tkatchenko-Scheffler (TS) methods, are tested on
      the A24, L7, and Taylor et al.'s "blind" test sets. It is found that for these
      systems, the vdW-DFs perform better that the TS methods. In particular, the vdW
      DF-cx functional gives binding energies that are the closest to the reference
      values, while the many-body correction of TS does not always lead to an
      improvement in the description of molecular systems. In light of these results,
      several directions for further improvements to describe van der Waals
      interactions are discussed.

PMID- 29448791
TI  - Energy decomposition analysis for exciplexes using absolutely localized molecular
      orbitals.
AB  - An energy decomposition analysis (EDA) scheme is developed for understanding the
      intermolecular interaction involving molecules in their excited states. The EDA
      utilizes absolutely localized molecular orbitals to define intermediate states
      and is compatible with excited state methods based on linear response theory such
      as configuration interaction singles and time-dependent density functional
      theory. The shift in excitation energy when an excited molecule interacts with
      the environment is decomposed into frozen, polarization, and charge transfer
      contributions, and the frozen term can be further separated into Pauli repulsion
      and electrostatics. These terms can be added to their counterparts obtained from
      the ground state EDA to form a decomposition of the total interaction energy. The
      EDA scheme is applied to study a variety of systems, including some model systems
      to demonstrate the correct behavior of all the proposed energy components as well
      as more realistic systems such as hydrogen-bonding complexes (e.g., formamide
      water, pyridine/pyrimidine-water) and halide (F-, Cl-)-water clusters that
      involve charge-transfer-to-solvent excitations.

PMID- 29448792
TI  - Nanoscale hydrodynamics near solids.
AB  - Density Functional Theory (DFT) is a successful and well-established theory for
      the study of the structure of simple and complex fluids at equilibrium. The
      theory has been generalized to dynamical situations when the underlying dynamics
      is diffusive as in, for example, colloidal systems. However, there is no such a
      clear foundation for Dynamic DFT (DDFT) for the case of simple fluids in contact
      with solid walls. In this work, we derive DDFT for simple fluids by including not
      only the mass density field but also the momentum density field of the fluid. The
      standard projection operator method based on the Kawasaki-Gunton operator is used
      for deriving the equations for the average value of these fields. The solid is
      described as featureless under the assumption that all the internal degrees of
      freedom of the solid relax much faster than those of the fluid (solid elasticity
      is irrelevant). The fluid moves according to a set of non-local hydrodynamic
      equations that include explicitly the forces due to the solid. These forces are
      of two types, reversible forces emerging from the free energy density functional,
      and accounting for impenetrability of the solid, and irreversible forces that
      involve the velocity of both the fluid and the solid. These forces are localized
      in the vicinity of the solid surface. The resulting hydrodynamic equations should
      allow one to study dynamical regimes of simple fluids in contact with solid
      objects in isothermal situations.

PMID- 29448793
TI  - Quantum dynamics of ClH2O- photodetachment: Isotope effect and impact of anion
      vibrational excitation.
AB  - Photodetachment of the ClH2O- anion is investigated using full-dimensional
      quantum mechanics on accurate potential energy surfaces of both the anion and
      neutral species. Detailed analysis of the photoelectron spectrum and the
      corresponding wavefunctions reveals that the photodetachment leads to, in the
      product channel of the exothermic HCl + OH -> Cl + H2O reaction, the formation of
      numerous Feshbach resonances due apparently to slow energy transfer from H2O
      vibrational modes to the dissociation coordinate. These long-lived resonances can
      be grouped into two broad peaks in the low-resolution photoelectron spectrum,
      which is in good agreement with available experiments, and they are assigned to
      the ground and first excited OH stretching vibrational manifolds of H2O complexed
      with Cl. In addition, effects of isotope substitution on the photoelectron
      spectrum were small. Finally, photodetachment of the vibrationally excited ClH2O-
      in the ionic hydrogen bond mode is found to lead to Feshbach resonances with
      higher stretching vibrational excitations in H2O.

PMID- 29448794
TI  - Short-time dynamics of lysozyme solutions with competing short-range attraction
      and long-range repulsion: Experiment and theory.
AB  - Recently, atypical static features of microstructural ordering in low-salinity
      lysozyme protein solutions have been extensively explored experimentally and
      explained theoretically based on a short-range attractive plus long-range
      repulsive (SALR) interaction potential. However, the protein dynamics and the
      relationship to the atypical SALR structure remain to be demonstrated. Here, the
      applicability of semi-analytic theoretical methods predicting diffusion
      properties and viscosity in isotropic particle suspensions to low-salinity
      lysozyme protein solutions is tested. Using the interaction potential parameters
      previously obtained from static structure factor measurements, our results of
      Monte Carlo simulations representing seven experimental lysoyzme samples indicate
      that they exist either in dispersed fluid or random percolated states. The self
      consistent Zerah-Hansen scheme is used to describe the static structure factor,
      S(q), which is the input to our calculation schemes for the short-time
      hydrodynamic function, H(q), and the zero-frequency viscosity eta. The schemes
      account for hydrodynamic interactions included on an approximate level.
      Theoretical predictions for H(q) as a function of the wavenumber q quantitatively
      agree with experimental results at small protein concentrations obtained using
      neutron spin echo measurements. At higher concentrations, qualitative agreement
      is preserved although the calculated hydrodynamic functions are overestimated. We
      attribute the differences for higher concentrations and lower temperatures to
      translational-rotational diffusion coupling induced by the shape and interaction
      anisotropy of particles and clusters, patchiness of the lysozyme particle
      surfaces, and the intra-cluster dynamics, features not included in our simple
      globular particle model. The theoretical results for the solution viscosity, eta,
      are in qualitative agreement with our experimental data even at higher
      concentrations. We demonstrate that semi-quantitative predictions of diffusion
      properties and viscosity of solutions of globular proteins are possible given
      only the equilibrium structure factor of proteins. Furthermore, we explore the
      effects of changing the attraction strength on H(q) and eta.

PMID- 29448795
TI  - Accelerated sampling by infinite swapping of path integral molecular dynamics
      with surface hopping.
AB  - To accelerate the thermal equilibrium sampling of multi-level quantum systems,
      the infinite swapping limit of a recently proposed multi-level ring polymer
      representation is investigated. In the infinite swapping limit, the ring polymer
      evolves according to an averaged Hamiltonian with respect to all possible surface
      index configurations of the ring polymer and thus connects the surface hopping
      approach to the mean-field path-integral molecular dynamics. A multiscale
      integrator for the infinite swapping limit is also proposed to enable efficient
      sampling based on the limiting dynamics. Numerical results demonstrate the huge
      improvement of sampling efficiency of the infinite swapping compared with the
      direct simulation of path-integral molecular dynamics with surface hopping.

PMID- 29448796
TI  - Detection of transient infrared absorption of SO3 and 1,3,2-dioxathietane-2,2
      dioxide [cyc-(CH2)O(SO2)O] in the reaction CH2OO+SO2.
AB  - We recorded time-resolved infrared absorption spectra of transient species
      produced on irradiation at 308 nm of a flowing mixture of CH2I2/O2/N2/SO2 at 298
      K. Bands of CH2OO were observed initially upon irradiation; their decrease in
      intensity was accompanied by the appearance of an intense band at 1391.5 cm-1
      that is associated with the degenerate SO-stretching mode of SO3, two major bands
      of HCHO at 1502 and 1745 cm-1, and five new bands near >1340, 1225, 1100, 940,
      and 880 cm-1. The band near 1340 cm-1 was interfered by absorption of SO2 and
      SO3, so its band maximum might be greater than 1340 cm-1. SO3 in its internally
      excited states was produced initially and became thermalized at a later period.
      The rotational contour of the band of thermalized SO3 agrees satisfactorily with
      the reported spectrum of SO3. These five new bands are tentatively assigned to an
      intermediate 1,3,2-dioxathietane-2,2-dioxide [cyc-(CH2)O(SO2)O] according to
      comparison with anharmonic vibrational wavenumbers and relative IR intensities
      predicted for this intermediate. Observation of a small amount of cyc
      (CH2)O(SO2)O is consistent with the expected reaction according to the potential
      energy scheme predicted previously. SO3+HCHO are the major products of the title
      reaction. The other predicted product channel HCOOH+SO2 was unobserved and its
      branching ratio was estimated to be <5%.

PMID- 29448797
TI  - Laser desorption vs. electrospray of polyyne-threaded rotaxanes: Preventing
      covalent cross-linking and promoting noncovalent aggregation.
AB  - Laser-induced cross-linking of polyynes is successfully hindered when the polyyne
      is encapsulated as part of a rotaxane and therefore protected by a surrounding
      macrocycle. When the rotaxane is electrosprayed, however, noncovalent aggregate
      ions are efficiently formed. Aggregates of considerable size (including more than
      50 rotaxane molecules with masses beyond 100k Da) and charge states (up to 13
      charges and beyond) have been observed. Either protons or sodium cations act as
      the charge carriers. These aggregates are not formed when the individual
      components of the rotaxane, i.e., the macrocycle or the polyyne, are separately
      electrosprayed. This underlines the structural importance of the rotaxane for the
      aggregate formation. Straightforward force field calculations indicate that the
      polyyne thread hinders the folding of the macrocycles, which facilitates the
      bonding interaction between the two components.

PMID- 29448798
TI  - Effect of alkaline metal cations on the ionic structure of cryolite melts: Ab
      initio NpT MD study.
AB  - Ab initio molecular dynamics simulations in an NpT ensemble have been performed
      to study the role of alkaline metal cations (Me = Li, Na, K, Rb) on the structure
      and vibrational properties of melts of Me-cryolites (Me3AlF6) at T = 1300 K. In
      all melts examined in this work, the species AlF52- has been found to be formed
      at the highest abundance [from 58% (Li) to 70% (Na)] among the Al-containing
      anionic clusters. The concentration of clusters AlF4- increases with the size of
      cations while that of anions AlF63- follows the opposite trend and it becomes
      negligible in the melts of the K- and Rb-cryolites. The computed percentage of
      the Al atoms participating in the formation of dimers Al2Fm6-m bridged via common
      F atoms is significant only in the case of Li- and Na-cryolites (16% and 10%,
      respectively) and the formation of even larger aggregates is found to be unlikely
      in all four melts. The percentage of the F atoms that are not bound to Al is ~20%
      in all four melts and the ions formed by Me+ and F- are found to be only short
      lived. Vibrational analysis has been performed using the velocity autocorrelation
      functions computed for the Cartesian and selected internal coordinates describing
      Raman-active symmetric stretching vibrations of different AlFn species. The
      results of vibrational analysis allowed us to identify trends in the variation of
      positions and shapes of peaks corresponding to the anionic fragments AlF4-, AlF52
      , and AlF63- with the size of cations, and these trends are found to be
      consistent with those deduced from the available Raman spectroscopy experiments.
      Our findings represent a new insight into the properties of cryolite melts, which
      will be useful for the interpretation of experimental data.

PMID- 29448799
TI  - Vibrational treatment of the formic acid double minimum case in valence
      coordinates.
AB  - One single full dimensional valence coordinate HCOOH ground state potential
      energy surface accurate for both cis and trans conformers for all levels up to
      6000 cm-1 relative to trans zero point energy has been generated at CCSD(T)
      F12a/aug-cc-pVTZ level. The fundamentals and a set of eigenfunctions complete up
      to about 3120 and 2660 cm-1 for trans- and cis-HCOOH, respectively, have been
      calculated and assigned using the improved relaxation method of the Heidelberg
      multi-configuration time-dependent Hartree package and an exact expression for
      the kinetic energy in valence coordinates generated by the TANA program. The
      calculated trans fundamental transition frequencies agree with experiment to
      within 5 cm-1. A few reassignments are suggested. Our results discard any cis
      trans delocalization effects for vibrational eigenfunctions up to 3640 cm-1
      relative to trans zero point energy.

PMID- 29448800
TI  - Classical coherent two-dimensional vibrational spectroscopy.
AB  - Two-dimensional (2D) ultrafast spectroscopy is a powerful tool for studying the
      electronic and vibrational structures of complex systems. Unfortunately, the
      physical interpretation of these experiments is obscured by conceptual problems
      in classical response theory, i.e., the divergence of classical nonlinear
      response functions. We demonstrate that these difficulties are avoided by
      modeling classical 2D experiments nonperturbatively, illustrating that nonlinear
      spectroscopy and nonlinear response are not synonymous. Numerical simulations
      allow a direct comparison between classical and quantum 2D spectra for simple,
      weakly anharmonic systems relevant to vibrational spectroscopy. We find that
      nonperturbative classical theory-although differing in quantitative details
      accurately captures the key qualitative features of the quantum 2D spectrum,
      including the separation of the signal into wavevector-selected pathways,
      formation of cross peaks between coupled vibrational modes, and coherent beating
      in the signal as a function of waiting time (so-called "quantum beats"). These
      results are discussed in terms of a simple analytical model which captures the
      key physical features of classical 2D spectroscopy and provides a link between
      classical and quantum descriptions. One interesting conclusion from this
      comparison is that the "coherence" observed in ultrafast spectroscopy may (at
      least in vibrational experiments) be understood as a purely classical phenomenon,
      without reference to quantum mechanics.

PMID- 29448801
TI  - Orientation-dependent imaging of electronically excited quantum dots.
AB  - We previously demonstrated that we can image electronic excitations of quantum
      dots by single-molecule absorption scanning tunneling microscopy (SMA-STM). With
      this technique, a modulated laser beam periodically saturates an electronic
      transition of a single nanoparticle, and the resulting tunneling current
      modulation DeltaI(x0, y0) maps out the SMA-STM image. In this paper, we first
      derive the basic theory to calculate DeltaI(x0, y0) in the one-electron
      approximation. For near-resonant tunneling through an empty orbital "i" of the
      nanostructure, the SMA-STM signal is approximately proportional to the electron
      density phiix0,y02 of the excited orbital in the tunneling region. Thus, the SMA
      STM signal is approximated by an orbital density map (ODM) of the resonantly
      excited orbital at energy Ei. The situation is more complex for correlated
      electron motion, but either way a slice through the excited electronic state
      structure in the tunneling region is imaged. We then show experimentally that we
      can nudge quantum dots on the surface and roll them, thus imaging excited state
      electronic structure of a single quantum dot at different orientations. We use
      density functional theory to model ODMs at various orientations, for qualitative
      comparison with the SMA-STM experiment. The model demonstrates that our
      experimentally observed signal monitors excited states, localized by defects near
      the surface of an individual quantum dot. The sub-nanometer super-resolution
      imaging technique demonstrated here could become useful for mapping out the three
      dimensional structure of excited states localized by defects within
      nanomaterials.

PMID- 29448802
TI  - B97-3c: A revised low-cost variant of the B97-D density functional method.
AB  - A revised version of the well-established B97-D density functional approximation
      with general applicability for chemical properties of large systems is proposed.
      Like B97-D, it is based on Becke's power-series ansatz from 1997 and is
      explicitly parametrized by including the standard D3 semi-classical dispersion
      correction. The orbitals are expanded in a modified valence triple-zeta Gaussian
      basis set, which is available for all elements up to Rn. Remaining basis set
      errors are mostly absorbed in the modified B97 parametrization, while an
      established atom-pairwise short-range potential is applied to correct for the
      systematically too long bonds of main group elements which are typical for most
      semi-local density functionals. The new composite scheme (termed B97-3c)
      completes the hierarchy of "low-cost" electronic structure methods, which are all
      mainly free of basis set superposition error and account for most interactions in
      a physically sound and asymptotically correct manner. B97-3c yields excellent
      molecular and condensed phase geometries, similar to most hybrid functionals
      evaluated in a larger basis set expansion. Results on the comprehensive GMTKN55
      energy database demonstrate its good performance for main group thermochemistry,
      kinetics, and non-covalent interactions, when compared to functionals of the same
      class. This also transfers to metal-organic reactions, which is a major area of
      applicability for semi-local functionals. B97-3c can be routinely applied to
      hundreds of atoms on a single processor and we suggest it as a robust
      computational tool, in particular, for more strongly correlated systems where our
      previously published "3c" schemes might be problematic.

PMID- 29448803
TI  - Pitfalls of big data.

PMID- 29448804
TI  - Cognitive behaviour therapy and inflammation: A systematic review of its
      relationship and the potential implications for the treatment of depression.

PMID- 29448805
TI  - Differentiating skull base chordomas and invasive pituitary adenomas with
      conventional MRI.
AB  - Background It is difficult to distinguish between invasive pituitary adenomas
      (IPAs) and skull base chordomas based on tumor location and clinical
      manifestations. Purpose To investigate the value of the apparent diffusion
      coefficient (ADC), T2-weighted (T2W) imaging, and dynamic contrast enhancement
      (DCE) in differentiating skull base chordomas and IPAs. Material and Methods Data
      for 21 patients with skull base chordomas and 27 patients with IPAs involving the
      paranasal sinus were retrospectively reviewed, and all diagnoses were
      pathologically confirmed. Each patient underwent conventional 3.0 T magnetic
      resonance imaging (MRI), including, ADC, T2W imaging, and DCE sequences. Regions
      of interest were drawn in the mass and in normal white matter on ADC maps and T2W
      imaging. The mean ADC, normal ADC, T2W imaging signal intensity (SI), and
      relative T2-weighted (rT2W) imaging values were measured. DCE parameters,
      including types of time signal-intensity curves (TIC), enhancement peak (EP), and
      maximum contrast enhancement ratio (MCER), were calculated. Differences between
      skull base chordomas and IPAs were evaluated using the independent samples t
      test. Receiver operating characteristic (ROC) curve analyses were also performed.
      Results When comparing IPAs and chordomas, there were significant differences in
      mean ADC, normal ADC, rT2W imaging values, TIC, EP, and MCER ( P < 0.01). The
      areas under curves in the ROC analyses for normal ADC, mean ADC, T2W imaging,
      rT2W imaging, TIC, EP, and MCER were 1.0, 0.996, 1.0, 0.81, 0.987, and 0.987,
      respectively. Conclusion ADC, T2W imaging SI, and DCE-related parameters can
      contribute to the differential diagnosis of skull base chordomas and IPAs.

PMID- 29448807
TI  - Editorial Comment on: MRI Displays the Prostatic Cancer Anatomy and Improves the
      Bundles Management Before Robot-Assisted Radical Prostatectomy by Schiavina et
      al.

PMID- 29448806
TI  - Endovascular treatment for the control of active vaginal bleeding from uterine
      cervical cancer treated with radiotherapy.
AB  - Background Endovascular treatment has become a significant therapeutic option for
      the management of intractable bleeding in gynecologic malignancies. However, the
      endovascular treatment types were almost never mentioned when active bleeding
      from different arteries was identified. Purpose To present angiographic details
      and evaluate clinical efficacy of endovascular treatments to control active
      vaginal bleeding in uterine cervical cancer patients treated with radiotherapy.
      Material and Methods In this retrospective study, six, consecutive cervical
      cancer patients treated with radiotherapy who underwent endovascular treatment
      for active vaginal bleeding were included. Angiographic findings, endovascular
      treatment details, and clinical outcomes were obtained. Results Ten endovascular
      procedures were technically successful, in which bleeding arteries were the
      internal iliac artery/its branches (n = 5), external iliac artery (EIA) (n = 3),
      uterine artery (n = 1), and superior rectal artery (n = 1), and bleeding
      manifested as contrast extravasation (n = 6), pseudoaneurysm (n = 1), or both (n
      = 3). Three of the four repeated procedures showed different bleeding sites from
      the primary ones. Stent graft was inserted to preserve the patency of the
      bleeding EIA in two patients. For another EIA rupture, both proximal and distal
      embolization were performed, followed by femoral-to-femoral bypass to preserve
      blood flow. Bleeding control within one month was achieved in 80% (8/10). One
      minor complication, mild transient pelvic pain, occurred in one patient.
      Conclusions Various endovascular treatment was feasible and effective to control
      active vaginal bleeding from cervical cancer. Repeated procedures showed commonly
      different bleeding foci and stent graft insertion was effective for preserving
      the patency of the large bleeding artery.

PMID- 29448808
TI  - Hypertension awareness, treatment and control in Ghana: a cross-sectional study.
AB  - OBJECTIVE: This study assessed the rates of hypertension awareness, treatment and
      control as well as the socio-economic and demographic correlates in Ghana.
      METHODS: This was a cross-sectional study. We used wave 1 of the World Health
      Organization (WHO) Study on global AGEing and adult health (SAGE) conducted
      between 2007and 2008. The sample was 5526 respondents aged 18 years and above.
      Descriptive statistics were used to describe the characteristics of the
      respondents and binary logistic regression was used to determine the correlates
      of hypertension awareness, treatment and control. RESULTS: The hypertension
      prevalence was 58.9%. About 19.0% of the individuals living with hypertension
      were aware of their hypertension; 67.6% of those who were aware of their
      hypertension were treating the condition, and; 11.6% of those who were on
      treatment had their hypertension controlled. Age, place of residence, level of
      education, employment status, ethnicity, and religion were associated with
      hypertension awareness and treatment. None of the factors was associated with
      hypertension control. CONCLUSION: Our study suggests high hypertension prevalence
      in Ghana, with low rates of awareness, treatment and control. Socio-economic and
      demographic factors are essential correlates of hypertension awareness and
      treatment in Ghana. The findings indicate the need to develop pragmatic
      intervention approaches such as rigorous education programs and use of the task
      shifting system, in addressing hypertension and issues related to it.

PMID- 29448809
TI  - Utilizing Machine Learning and Automated Performance Metrics to Evaluate Robot
      Assisted Radical Prostatectomy Performance and Predict Outcomes.
AB  - PURPOSE: Surgical performance is critical for clinical outcomes. We present a
      novel machine learning (ML) method of processing automated performance metrics
      (APMs) to evaluate surgical performance and predict clinical outcomes after robot
      assisted radical prostatectomy (RARP). MATERIALS AND METHODS: We trained three ML
      algorithms utilizing APMs directly from robot system data (training material) and
      hospital length of stay (LOS; training label) (<=2 days and >2 days) from 78 RARP
      cases, and selected the algorithm with the best performance. The selected
      algorithm categorized the cases as "Predicted as expected LOS (pExp-LOS)" and
      "Predicted as extended LOS (pExt-LOS)." We compared postoperative outcomes of the
      two groups (Kruskal-Wallis/Fisher's exact tests). The algorithm then predicted
      individual clinical outcomes, which we compared with actual outcomes (Spearman's
      correlation/Fisher's exact tests). Finally, we identified five most relevant APMs
      adopted by the algorithm during predicting. RESULTS: The "Random Forest-50" (RF
      50) algorithm had the best performance, reaching 87.2% accuracy in predicting LOS
      (73 cases as "pExp-LOS" and 5 cases as "pExt-LOS"). The "pExp-LOS" cases
      outperformed the "pExt-LOS" cases in surgery time (3.7 hours vs 4.6 hours, p =
      0.007), LOS (2 days vs 4 days, p = 0.02), and Foley duration (9 days vs 14 days,
      p = 0.02). Patient outcomes predicted by the algorithm had significant
      association with the "ground truth" in surgery time (p < 0.001, r = 0.73), LOS (p
      = 0.05, r = 0.52), and Foley duration (p < 0.001, r = 0.45). The five most
      relevant APMs, adopted by the RF-50 algorithm in predicting, were largely related
      to camera manipulation. CONCLUSION: To our knowledge, ours is the first study to
      show that APMs and ML algorithms may help assess surgical RARP performance and
      predict clinical outcomes. With further accrual of clinical data (oncologic and
      functional data), this process will become increasingly relevant and valuable in
      surgical assessment and training.

PMID- 29448810
TI  - Safety and effectiveness of zotarolimus-eluting stents for percutaneous coronary
      intervention: a systematic review.
AB  - Drug-eluting stents revolutionized the treatment of coronary artery disease with
      vastly improved outcomes compared with bare metal stents. As stent technology has
      evolved, a wide variety of antiproliferative drugs have been developed to prevent
      stent restenosis and stent thrombosis. The Resolute stent system (Medtronic, CA,
      USA) elutes zotarolimus from a multipolymer blend to prevent early and late stent
      related complications. The Resolute stents have evolved from the initial Resolute
      stent, to the Resolute IntegrityTM and most recently, the Resolute OnyxTM. These
      stents have been studied across a wide range of patients and coronary syndromes.
      They compare similarly in performance to their contemporary second generation
      stents. We present a review of the major trials involving these zotarolimus
      eluting stents.

PMID- 29448811
TI  - Production of a new mucilage compound in Lepidium sativum callus by optimizing in
      vitro growth conditions.
AB  - The mucilage in Lepidium sativum L. is considered a biologically active compound
      with diverse medicinal properties. Different explants (hypocotyls and leaf) were
      transferred to Murashige and Skoog (MS) medium supplemented with twelve different
      plant growth regulator combinations under two different incubations (light and
      dark). The best mucilage production from callus (36.76% g g-1 dry weight) was
      obtained in the MS medium supplemented with 1 mg L-1 of 2, 4-D and 2 mg L-1 of
      BAP under the light condition. The mucilage produced by callus culture was nearly
      three times more than the mucilage yield of the seeds. The glucose, arabinose +
      mannose and galactose were 43.4 (mg g-1 DW), 195.3 (mg g-1 DW) and 86.2 (mg g-1
      DW) in the mucilage originated from seed, callus leaf and callus hypocotyl,
      respectively. The present study proposes an efficient method for producing large
      scales of mucilage with a favorable sugar aimed at food or pharmaceutical
      industries.

PMID- 29448812
TI  - A Qualitative Examination of Parent Engagement in a Family-Based Childhood
      Obesity Program.
AB  - Low parent engagement is frequently identified as a barrier to effective
      implementation of family-based childhood obesity prevention and control programs.
      A more nuanced understanding of factors affecting parent engagement is important
      for improving implementation and, ultimately, program efficacy. This qualitative
      study examined factors influencing parent engagement in a family-based childhood
      obesity prevention and control program. Semistructured interviews informed by the
      health belief model and the transtheoretical model were conducted with 22
      predominantly Latina mothers following the scheduled conclusion of program
      activities. Spanish- and English-language interviews were transcribed, translated
      into English (if Spanish), coded, and summarized using established protocols.
      Differences between parents who attended at least two thirds of program
      activities and those who did not were examined. There were no significant
      demographic differences between parents who did and did not complete two thirds
      of program activities. Findings indicated that differences in parent engagement
      may be at least partially explained by differences in parental motivations for
      participating and in barriers and facilitators, such as children's level of
      support and enthusiasm for the program. Parents were highly satisfied with the
      program content and the community health workers who delivered the program. This
      study adds to emergent literature regarding parents' experiences in family-based
      childhood obesity prevention and control programs. Potential targets for
      improving program engagement are discussed.

PMID- 29448813
TI  - Biofouling in membrane bioreactors: nexus between polyacrylonitrile surface
      charge and community composition.
AB  - The influence of membrane surface charge on biofouling community composition
      during activated sludge filtration in a membrane bioreactor was investigated in
      this study using polyacrylonitrile-based membranes. Membranes with different
      surface properties were synthesized by phase inversion followed by a layer-by
      layer modification. Various characterization results showed that the membranes
      differed only in their surface chemical composition and charge, ie two of them
      were negative, one neutral and one positive. Membrane fouling experiments were
      performed for 40 days and the biofouling communities were analyzed. PCR-DGGE
      fingerprinting indicated selective enrichment of bacterial populations from the
      sludge suspension within the biofilms at any time point. The biofilm community
      composition seemed to change with time. However, no difference was observed
      between the biofilm community of differently charged membranes at specific time
      points. It could be concluded that membrane charges do not play a decisive role
      in the long-term selection of the key bacterial foulants.

PMID- 29448814
TI  - Measuring Prosociality: The Development of a Prosocial Behavioral Intentions
      Scale.
AB  - Prosociality is a critical issue in behavioral research. In this investigation,
      we developed a measure of prosocial behavioral intentions. Qualitative responses
      from two surveys (n = 465) and items from existing measures were used to generate
      a list of prosocial behaviors in which people might intend to engage. We factor
      analyzed responses to these items (n = 319) and retained the most common and
      representative items. The new measure demonstrated adequate internal consistency
      (n = 247, 147; alpha = .81, .83); convergent validity with past prosocial
      behavior (r = .51, .43), moral identity (r = .50, .55), and materialism (r = 
      .30, -.20). The instrument also predicted prosocial behavior while controlling
      for a prior measure of prosocial intentions, Exp(B) = 1.99, Wald = 10.59, p =
      .001, thereby demonstrating incremental predictive validity. This 4-item scale
      could be used across contexts to advance the study of prosociality.

PMID- 29448815
TI  - Topiramate-Induced Acne in a 31-Year-Old Woman: A Case Report.

PMID- 29448816
TI  - Using Cartilage MRI T2-Mapping to Analyze Early Cartilage Degeneration in the
      Knee Joint of Young Professional Soccer Players.
AB  - Objective To evaluate and characterize the appearance of articular cartilage in
      the tibiofemoral joint of young professional soccer players using T2-relaxation
      time evaluation on magnetic resonance imaging (MRI). Design In this study, we
      included 57 male adolescents from the youth academy of a professional soccer
      team. The MRI scans were acquired of the knee joint of the supporting leg. An
      "early unloading" (minute 0) and "late unloading" (minute 28) T2-sequence was
      included in the set of images. Quantitative T2-analysis was performed in the
      femorotibial joint cartilage in 4 slices with each 10 regions of interest (ROIs).
      Statistical evaluation, using Wilcoxon signed-rank tests, was primarily performed
      to compare the T2 values of the "early unloading" and "late unloading." Results
      When comparing "early unloading" with "late unloading," our findings showed a
      significant increase of T2-relaxation times in the weightbearing femoral
      cartilage of the medial ( P < 0.001) and lateral ( P < 0.001) compartment of the
      knee and in the tibial cartilage of the medial compartment ( P < 0.001).
      Conclusion In this study, alterations of the cartilage were found with a maximum
      in the medial condyle where the biomechanical load of the knee joint is highest,
      as well as where most of the chronic cartilage lesions occur. To avoid chronic
      damage, special focus should be laid on this region.

PMID- 29448817
TI  - Treating Severe Knee Osteoarthritis with Combination of Intra-Osseous and Intra
      Articular Infiltrations of Platelet-Rich Plasma: An Observational Study.
AB  - Objective Assessing the therapeutic effects of a combination of intra-articular
      and intra-osseous infiltrations of platelet-rich plasma (PRP) to treat severe
      knee osteoarthritis (KOA) using intra-articular injections of PRP as the control
      group. Design In this observational study, 60 patients suffering from severe KOA
      were treated with intra-articular infiltrations of PRP (IA group) or with a
      combination of intra-osseous and intra-articular infiltrations of PRP (IO group).
      Both groups were matched for sex, age, body mass index, and radiographic severity
      (III and IV degree according to Ahlback scale). Clinical outcome was evaluated at
      2, 6, and 12 months, using the Knee injury and Osteoarthritis Outcome Score
      (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
      questionnaires. Results At 2, 6 and 12 months after treatment, IO group had a
      significant improvement in all KOOS and WOMAC subscales ( P < 0.05). On the
      contrary, patients of the IA group did not improve in any of the scores. Sixteen
      out of 30 IO group patients showed minimal clinically important improvement
      (MCII) whereas 8 out of 30 IA group patients showed this response at 6 months
      (26.7%; 95% CI -0.4 to 49.9; P = 0.037). At 12 months, 14 patients of IO group
      and 5 patients of the IA group showed MCII (30%; 95% CI 4.3 to 51.9; P = 0.013).
      No differences between groups were observed at 2 months. Conclusions PRP intra
      articular injections in severe KOA were not effective and did not provide any
      benefit. Combination of intra-articular and intra-osseous infiltrations of PRP
      was not clinically superior at 2 months, but it showed superior clinical outcomes
      at 6 and 12 months when compared with intra-articular injections of PRP.

PMID- 29448818
TI  - Managing in-hospital quality improvement: An importance-performance analysis to
      set priorities for ST-elevation myocardial infarction care.
AB  - BACKGROUND: A focus on specific priorities increases the success rate of quality
      improvement efforts for broad and complex-care processes. Importance-performance
      analysis presents a possible approach to set priorities around which to design
      and implement effective quality improvement initiatives. Persistent variation in
      hospital performance makes ST-elevation myocardial infarction care relevant to
      consider for importance-performance analysis. AIMS: The purpose of this study was
      to identify quality improvement priorities in ST-elevation myocardial infarction
      care. METHODS: Importance and performance levels of ST-elevation myocardial
      infarction key interventions were combined in an importance-performance analysis.
      Content validity indexes on 23 ST-elevation myocardial infarction key
      interventions of a multidisciplinary RAND Delphi Survey defined importance
      levels. Structured review of 300 patient records in 15 acute hospitals determined
      performance levels. The significance of between-hospital variation was determined
      by a Kruskal-Wallis test. A performance heat-map allowed for hospital-specific
      priority setting. RESULTS: Seven key interventions were each rated as an overall
      improvement priority. Priority key interventions related to risk assessment,
      timely reperfusion by percutaneous coronary intervention and secondary
      prevention. Between-hospital performance varied significantly for the majority of
      key interventions. The type and number of priorities varied strongly across
      hospitals. CONCLUSIONS: Guideline adherence in ST-elevation myocardial infarction
      care is low and improvement priorities vary between hospitals. Importance
      performance analysis helps clinicians and management in demarcation of the
      nature, number and order of improvement priorities. By offering a tailored
      improvement focus, this methodology makes improvement efforts more specific and
      achievable.

PMID- 29448819
TI  - Identifying the inhibition of TIR proteins involved in TLR signalling as an anti
      inflammatory strategy.
AB  - Toll/IL1 receptor (TIR) adaptor proteins continue to be an integral part of Toll
      like receptors' (TLR) signalling involved in inflammation. Signalling is likely
      to be initiated by these TIR adaptors when they are recruited to a TIR-TIR
      interface formed by TLR dimerization. Among these, myeloid differentiation factor
      88 (MyD88), MyD88 adapter-like protein (Mal), TIR domain-containing adaptor
      protein inducing interferon-beta (TRIF) and TRIF-related adaptor molecule (TRAM)
      play pivotal roles at many steps in the signalling events leading to
      inflammation. The presence of the conserved BB loop residues in the TIR domain of
      all these important adaptor proteins make them possible targets for inhibition by
      synthetic compounds. We have designed compounds based on an already known MyD88
      TIR dimerization inhibitor, T6167923, which binds well not only to the original
      target but also to the TIR domains of Mal, TRIF and TRAM. The designed inhibitors
      are based on modifications of the bromophenyl-sulphonyl-thiophenyl-piperazine
      carboxamide series of compounds. We have further suggested modifications in these
      high-affinity compounds for efficient absorption inside the body. Further, a
      pharmacophore model highlighting important structural interaction features has
      been developed. The screened compounds are better in binding to the TIR proteins
      then the parent compound and hence are good starting points for multi-TIR
      inhibition.

PMID- 29448820
TI  - Evaluating the reporting of adverse events in controlled clinical trials
      conducted in 2010-2015 on migraine drug treatments.
AB  - Background In 2008, the International Headache Society published guidelines on
      the "evaluation and registration of adverse events in clinical drug trials on
      migraine". They listed seven recommendations for reporting adverse events in
      randomized controlled trials on migraine. The present study aimed to evaluate
      adherence to these recommendations, and based on the results, to recommend
      improvements. Methods We searched the PubMed/MEDLINE database to identify
      controlled trials on migraine drugs published from 2010 to 2015. For each trial,
      we noted whether five of the recommended parameters were presented. In addition,
      we noted whether adverse events were reported in abstracts. Results We identified
      73 trials; 51 studied acutely administered drugs and 22 studied prophylactic
      drugs for migraine. The number of patients with any adverse events were reported
      in 74% of acute-administration and 86% of prophylactic drug trials. Only 30 (41%)
      of the 73 studies reported adverse events with data in the abstracts, and 27
      (37%) abstracts did not mention adverse events. Conclusion Adverse events, both
      frequency and symptoms, should be reported to allow a fair judgement of
      benefit/tolerability ratio when randomized controlled trials in migraine
      treatment are published. Clinically significant adverse events should be included
      in the abstract of every randomized controlled trial in migraine treatment.

PMID- 29448822
TI  - Ice-liquid isotope fractionation factors for 18O and 2H deduced from the isotopic
      correction constants for the triple point of water.
AB  - The stable isotopes of water are extensively used as tracers in many fields of
      research. For this use, it is essential to know the isotope fractionation factors
      connected to various processes, the most important of which being phase changes.
      Many experimental studies have been performed on phase change fractionation over
      the last decades. Whereas liquid-vapour fractionation measurements are relatively
      straightforward, vapour-solid and liquid-solid fractionation measurements are
      more complicated, as maintaining equilibrium conditions when a solid is involved
      is difficult. In this work, we determine the ice-liquid isotope fractionation
      factors in an indirect way, by applying the Van't Hoff equation. This equation
      describes the relationship of the fractionation factors with isotope-dependent
      temperature changes. We apply it to the recently experimentally determined
      isotope dependences of the triple point temperature of water [Faghihi V, Peruzzi
      A, Aerts-Bijma AT, et al. Accurate experimental determination of the isotope
      effects on the triple point temperature of water. I. Dependence on the 2H
      abundance. Metrologia. 2015;52:819-826; Faghihi V, Kozicki M, Aerts-Bijma AT, et
      al. Accurate experimental determination of the isotope effects on the triple
      point temperature of water. II. Combined dependence on the 18O and 17O
      abundances. Metrologia. 2015;52:827-834]. This results in new values for the 2H
      (deuterium) and 18O fractionation factors for the liquid-solid phase change of
      water, which agree well with existing, direct experimental data [Lehmann M,
      Siegenthaler U. Equilibrium oxygen- and hydrogen-isotope fractionation between
      ice and water. J Glaciol. 1991;37:23-26]. For 2H, the uncertainty is improved by
      a factor of 3, whereas for 18O the uncertainty is similar. Our final results are
      alphaS-L (2H/1H) = 1.02093(13), and alphaS-L (18O/16O) = 1.002909(25), where the
      latter is the weighted average of the previous experimental study and this work.

PMID- 29448823
TI  - Chemical constituents of Genista numidica Spach aerial parts and their
      antimicrobial, antioxidant and antityrosinase activities.
AB  - A previously undescribed triterpenoid saponin, 3-O-[alpha-l-rhamnopyranosyl-(1
      >2)-{beta-d-glucopyranosyl-(1->6)-}beta-d-galactopyranosyl-(1->2)-beta-d
      glucuronopyranosyl]-sophoradiol (1), in addition to twenty-nine known
      constituents (2-30) were isolated from the aerial parts of Genista numidica
      Spach. Structures elucidation was performed by comprehensive 1D- and 2D-NMR
      analyses and HRESIMS. The extracts, fractions and isolated compounds were
      evaluated for their antibacterial, antioxidant and tyrosinase inhibitory
      activities. The experimental findings indicated that genistin (16), isosalipurpol
      (27), and koaburaside (29) have moderate to low antibacterial activity against E.
      faecalis, S. aureus, S. epidermidis and P. aeruginosa bacteria with MICs ranging
      from 31.2 to 125 MUg/mL. Compounds 19 and 27 exhibited a good antiradical
      activity potential (IC50 11.8 and 11.1 MUg/mL, respectively). Only compounds 23,
      27 and 28 exhibited low inhibitory effect against mushroom tyrosinase (IC50 from
      90.2 to 225.6 MUg/mL).

PMID- 29448824
TI  - Influence of Diagnosis and Other Factors on Patients' Expectations of Foot and
      Ankle Surgery.
AB  - BACKGROUND: Many patient factors have been associated with higher or lower
      expectations of orthopedic surgery. In foot and ankle surgery, the diverse
      diagnoses seen may also influence expectations. The aim of this study was to
      investigate the relationship between diagnosis and patients' preoperative
      expectations of elective foot and ankle surgery. METHODS: Two hundred seventy
      eight patients undergoing elective foot or ankle surgery for 1 of 7 common
      diagnoses were enrolled in a prospective cohort study. Preoperative expectations
      were assessed with the Hospital for Special Surgery Foot & Ankle Surgery
      Expectations Survey. Patients also completed the Foot & Ankle Outcome Score,
      Short Form 12, pain visual analog scale, and questionnaires for depressive and
      anxiety symptoms. Demographic and clinical data were collected. Patient factors
      and diagnosis were analyzed using multivariate regression analysis to identify
      independent predictors of higher expectations and determine the effect of
      diagnosis relative to other patient factors on expectations. RESULTS: The
      multivariate regression analysis adjusting for demographics and other clinical
      characteristics showed that diagnosis contributed the most to the model,
      accounting for 10.5% of the variation in expectations survey scores. Patients
      with mid- or hindfoot arthritis ( P < .001), hallux valgus ( P = .001), or hallux
      rigidus ( P = .005) had lower scores (lower expectations) than those with ankle
      instability or osteochondral lesion. In the model, female sex ( P = .001), non
      Caucasian race ( P = .031), and lower scores on the Foot & Ankle Outcome Score
      daily activities subscale ( P = .024) were associated with higher scores.
      CONCLUSIONS: Diagnosis of ankle instability or osteochondral lesion, female sex,
      non-Caucasian race, and lower Foot & Ankle Outcome Score daily activities
      subscale score were all associated with higher expectations. These findings may
      help inform and guide surgeons as they counsel patients preoperatively. LEVEL OF
      EVIDENCE: Level II, cross-sectional study.

PMID- 29448825
TI  - Radiographic Prognostic Factors for Selective Soft Tissue Release After Ponseti
      Failure in Young Pediatric Clubfoot Patients.
AB  - BACKGROUND: Selective soft tissue release (SSTR), which includes a combination of
      abductor hallucis, tibialis posterior, and Achilles lengthening, has been used in
      patients with recurrent clubfoot deformity after Ponseti treatment. The aim of
      this study was to investigate the prognostic factors for recurrence of clubfoot
      deformity after SSTR. METHODS: Consecutive patients with idiopathic clubfoot and
      residual or recurrent deformity after Ponseti treatment underwent SSTR between
      2005 and 2013. The clinical and radiologic characteristics before and after SSTR
      were analyzed. The ability of radiologic factors to predict recurrence of
      clubfoot deformity was assessed using multivariate analysis. Rigid deformities of
      forefoot adduction, and hindfoot varus, and equinus were examined separately.
      Forty-three patients with 64 clubfeet were included. RESULTS: Postoperative
      improvement in the talo-first metatarsal angle on the anteroposterior view, the
      talocalcaneal angle on the lateral view, and the tibiocalcaneal angle on the
      lateral view independently predicted recurrence after SSTR. Additionally, the
      preoperative talocalcaneal angles on the anteroposterior and lateral views were
      also significant predictors, but these angles did not significantly improve after
      SSTR. CONCLUSIONS: SSTR seems to be an effective surgical modality only in milder
      deformities. Among patients with poor talocalcaneal angles, a high percentage
      required further surgery. The present results may be useful for the choice of
      SSTR or more extensive surgery. LEVEL OF EVIDENCE: Level III, retrospective case
      control study.

PMID- 29448826
TI  - Complications of Supine Surgical Achilles Tendon Repair.
AB  - BACKGROUND: Open Achilles tendon surgery with the patient in the supine position
      potentially avoids the complications of the prone position, but the safety and
      viability of the supine position for this procedure are not known. The aim of
      this study was to test the hypothesis that supine positioning for open repair of
      acute Achilles tendon ruptures would be safe, with low wound and neurologic
      complication rates. METHODS: Supine position safety in acute Achilles tendon
      repair was investigated. Consecutive cases of supine Achilles tendon surgical
      repair performed by one surgeon from 2010 to 2015 were retrospectively reviewed.
      Patients were included if they were surgically treated with primary repair in the
      supine position within 15 days of injury and did not undergo concomitant surgery.
      A paramedian incision 1 cm medial to the Achilles sheath was used. Initial chart
      review identified 161 patients who underwent any type of Achilles tendon surgery
      in the supine position, of whom 45 patients met the inclusion criteria. This
      group included 39 men and 6 women with an average age of 41 years (range, 20-66
      years). Median length of follow-up was 116 days (range, 25-1,589 days). Average
      body mass index was 29 kg/m2 (range, 23-36 kg/m2). RESULTS: There were no
      infections, sural nerve injuries, or reruptures. CONCLUSIONS: The supine position
      was safe for primary open Achilles tendon repair, with no wound or neurologic
      complications. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 29448827
TI  - Outcomes After Primary Repair of Insertional Ruptures of the Achilles Tendon.
AB  - BACKGROUND: Achilles tendon insertional sleeve avulsions occur when the Achilles
      distal tendon sleeve ruptures off of its insertion into the calcaneal tuberosity,
      sometimes with a small bony fragment from calcific tendinosis. Little evidence
      exists describing the outcomes and rerupture rate after operative management of
      Achilles tendon sleeve avulsions. METHODS: A retrospective chart review was
      performed to identify patients who sustained an Achilles sleeve avulsion injury
      treated with operative repair between October 2005 and July 2014. A cohort of 16
      patients from the general population and 12 professional athletes were included
      in the study. The primary outcome variable was rerupture of the Achilles tendon
      or need for revision surgery. Secondary outcome variables included the Coughlin
      Satisfaction Scale, visual VR-12, and Foot and Ankle Ability Measure (FAAM).
      RESULTS: In the general population cohort, median follow-up was 8.1 years (range,
      3.2-11.1 years). The median FAAM Activities of Daily Living score was 100 (range,
      42.9-106), and the median FAAM Sports score was 100 (range, 7.1-103.6). The
      median VR-12 Mental Component Score was 66.9 (range, 45.6-71.8), and the median
      VR-12 Physical Component Score was 53 (range, 30.8-57.5). In the cohort of
      professional athletes, preceding insertional Achilles symptoms were present in
      91.7% (11/12) of athletes for more than 9 months prior to rupture. All athletes
      returned to play with an average time of 13.4 months. No patients sustained a
      rerupture in the follow-up period. CONCLUSION: Operative repair of Achilles
      tendon sleeve avulsions was safe and effective with high patient satisfaction and
      good clinical outcomes in patients from the general population. LEVEL OF
      EVIDENCE: Level IV, retrospective case series.

PMID- 29448828
TI  - Role of terminal warm blood cardioplegia in complex congenital heart surgery.
AB  - Introduction Myocardial protection is vital to ensure successful open heart
      surgery. Cardioplegic solution is one method to achieve good myocardial
      protection. Inevitably, ischemia-reperfusion injury occurs with aortic
      crossclamping. Histidine-tryptophan-ketoglutarate solution is a frequently used
      cardioplegia for complex congenital heart surgery. We postulated that addition of
      terminal warm blood cardioplegia before removal of the aortic crossclamp might
      improve myocardial protection. Method A randomized controlled trial was conducted
      on 109 cyanotic patients aged, 1 to 5 years who underwent complex biventricular
      repair. They were divided into a control group of 55 patients who had histidine
      tryptophan-ketoglutarate only and a treatment group of 54 who had histidine
      tryptophan-ketoglutarate with terminal warm blood cardioplegia. Endpoints were
      clinical parameters, troponin I levels, and caspase-3 as an apoptosis marker.
      Results The incidence of low cardiac output syndrome was 34%, with no significant
      difference between groups (35.2% vs. 33.3%, p = 0.84). The incidence of
      arrhythmias in our treatment group was lower compared to the control group (36%
      vs. 12%, p = 0.005). Troponin I and caspase-3 results did not show any
      significant differences between groups. For cases with Aristotle score >= 10,
      weak expression of caspase-3 in the treatment group post-cardiopulmonary bypass
      was lower compared to the control group. Conclusion For complex congenital
      cardiac surgery, the addition of terminal warm blood cardioplegia does not
      significantly improve postoperative clinical or metabolic markers.

PMID- 29448829
TI  - Lung herniation or subcutaneous emphysema after cardiopulmonary resuscitation?

PMID- 29448830
TI  - Pulmonary mucormycosis mimicking an endobronchial mass.
AB  - Mucormycosis is an opportunistic fungal infection that can infect different
      regions of the body. This entity may present in rhinocerebral, pulmonary,
      cutaneous, and disseminated forms. Although pulmonary mucormycosis is usually
      seen as an invasive parenchymal consolidation or cavitation, it may rarely
      present as an endobronchial mass. We describe a case of endobronchial
      mucormycosis in which the fungal mass was completely removed via rigid
      bronchoscopy before medical therapy.

PMID- 29448831
TI  - Pleural drainage using drainage bag for thoracoscopic lobectomy.
AB  - Objective This study was designed to compare the effectiveness and convenience of
      a drainage bag and a chest bottle following thoracoscopic lobectomy. Methods We
      conducted a test to ensure that the drainage bag was characterized by easy
      drainage and an antireflux effect. Thereafter, the drainage bag was used in all
      thoracic operations in our service. To understand the usefulness of the drainage
      bag, a retrospective cohort study enrolled 30 patients who had a drainage bag
      after thoracoscopic lobectomy and compared them with 30 similar patients operated
      on previously who had chest bottles. Variables studied included total drainage
      volume, duration of drainage, complications, and satisfaction of the care
      providers. Results There was no significant difference between the chest bottle
      and drainage bag groups respectively in terms of total drainage (697.5 +/- 89.7
      vs. 614.1 +/- 76.6 mL, p = 0.483) or duration of drainage (4.23 +/- 0.38 vs. 4.43
      +/- 0.38 days, p = 0.713). No device-related complication was observed. After our
      experience with the drainage bag, we abandoned use of the chest bottle. The
      drainage bag was more convenient for patients and promoted early ambulation as
      well improving cost effectiveness. Most care providers preferred to use the
      drainage bag (p = 0.000). Conclusion The drainage bag is superior to the chest
      bottle for postoperative drainage.

PMID- 29448832
TI  - Bland or tumor pulmonary artery stump thrombosis?

PMID- 29448833
TI  - Efficacy and safety of luseogliflozin added to insulin therapy in Japanese
      patients with type 2 diabetes: a multicenter, 52-week, clinical study with a 16
      week, double-blind period and a 36-week, open-label period.
AB  - OBJECTIVE: To evaluate the efficacy and safety of luseogliflozin in Japanese
      patients with type 2 diabetes (T2D) inadequately controlled with insulin
      monotherapy. METHODS: This 52-week multicenter study entailed a 16-week, double
      blind period followed by a 36-week, open-label period. Patients were randomized
      to receive either luseogliflozin 2.5 mg (n = 159) or placebo (n = 74) during the
      double-blind period. All patients who entered the open-label period received
      luseogliflozin. Major efficacy endpoints included the changes from baseline in
      HbA1c, fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and
      bodyweight. Safety assessments included adverse events, laboratory tests and
      vital signs. RESULTS: In the double-blind period, luseogliflozin significantly
      decreased HbA1c (-1.18%), FPG (-42.4 mg/dL), 2 hour PPG (-68.7 mg/dL) and
      bodyweight (-1.27 kg) compared with placebo (all p < .001); these reductions were
      maintained over 52 weeks. The changes from baseline at Week 52 were -1.00%, -35.1
      mg/dL, -68.8 mg/dL and -1.81 kg, respectively (all p < .001). In the placebo
      group, favorable glycemic control and bodyweight reduction were also observed
      after switching to luseogliflozin. Most adverse events were mild in severity.
      During the double-blind period, the incidences of hypoglycemia were 20.8% and
      13.5% in the luseogliflozin and placebo groups, respectively. During the 52 weeks
      of luseogliflozin treatment, the frequency of hypoglycemia was 33.3%, but no
      serious hypoglycemia occurred. The safety profile other than hypoglycemia was
      also acceptable. There were no new safety concerns about luseogliflozin added to
      insulin. CONCLUSION: Luseogliflozin added to insulin therapy significantly
      improved glycemic control with bodyweight reduction and was well tolerated in
      Japanese patients with T2D. CLINICAL TRIAL REGISTRATION: Japan Pharmaceutical
      Information Center (JapicCTI-142582).

PMID- 29448834
TI  - Single-Occupancy Patient Rooms: A Systematic Review of the Literature Since 2006.
AB  - AIM: Our review evaluated both the effects of single-occupancy patient rooms
      (SPRs) on patient outcomes for hospitalized adults and user opinion related to
      SPRs. BACKGROUND: In 2006, a requirement for SPRs in hospitals was instituted in
      the United States. This systematic literature review evaluates research published
      since that time to evaluate the impact of SPRs. METHODS: The review adheres to
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
      Databases searched included MEDLINE, CINAHL, and Scopus. Supplemental searches
      were performed. We included studies reporting patient outcomes or user opinion
      related to SPRs. Appraisal was conducted using a dual appraisal system of
      evidence levels and methodological quality. RESULTS: Forty-three studies
      qualified for appraisal. Three were excluded due to methodological quality (no
      appraisal score). One study was appraised for three individual outcomes (i.e.,
      falls, infections, and user opinion). Eleven studies with low methodological
      quality scores were not included in the narrative synthesis. Overall, 87% of
      studies reported advantages associated with SPRs (some a combination of
      advantages and disadvantages or a combination of advantages and neutral results).
      Outcomes with the best evidence of benefit include communication, infection
      control, noise reduction/perceived sleep quality, and preference/perception.
      CONCLUSION: SPRs seem to result in more advantages than disadvantages. However,
      healthcare is a complex adaptive system, and decisions for 100% SPRs should be
      reviewed alongside related issues, such as necessary workflow modifications, unit
      configuration and other room layout decisions, patient populations, staffing
      models, and inherent trade-offs (e.g., the advantages of privacy compared to
      disadvantage of isolation).

PMID- 29448835
TI  - Here's Some Great Research! Now What? Translating Research Into Practice.

PMID- 29448836
TI  - AAV8 Gene Therapy Rescues the Newborn Phenotype of a Mouse Model of Crigler
      Najjar.
AB  - Adeno-associated viral (AAV) vectors can target the liver, making them an
      attractive platform for gene therapy approaches that require the correction of
      hepatocytes. Crigler-Najjar syndrome is an autosomal recessive disorder of
      bilirubin metabolism that occurs when the liver's uridine diphosphate
      glucuronosyl transferase 1A1 (UGT1A1) enzyme activity is partially or completely
      absent. This syndrome is characterized by elevated bilirubin levels in the blood.
      An AAV8 vector was developed expressing a codon-optimized human version of UGT1A1
      from a liver-specific promoter. High doses of the vector rescued neonatal
      lethality in newborn UGT1 knockout (KO) mice, which serve as a model of Crigler
      Najjar syndrome, and significantly increased survival from 5 to 270 days. Newborn
      UGT1 KO mice treated with AAV had serum total bilirubin levels that were 5.7
      times higher than the levels seen in heterozygous and wild-type mice, likely due
      to dilution of vector genome copies (GC) in the liver resulting from a
      proliferation of hepatocytes during growth of the animal. The elevation in serum
      total bilirubin levels in adult UGT1 KO mice depended on the AAV8 vector dose. At
      doses <1011 GC/mouse, total bilirubin levels returned to those seen in
      phototherapy-rescued UGT1 KO mice. Mice injected with vector at 1011 or 3 * 1011
      GC/mouse had sustained reduced total bilirubin levels throughout the duration of
      the study. When an AAV8 vector was re-administered in mice with elevated total
      bilirubin levels, serum total bilirubin levels decreased to wild-type levels (0.1
      0.3 mg/dL) in mice that received a vector dose of 3 * 1012 GC/kg. Therefore, a
      low-level and likely transient decrease in serum total bilirubin during the first
      days of life is necessary for rescuing the lethal phenotype present in the
      neonatal UGT1 KO mouse. Furthermore, it was possible to ablate the elevated total
      bilirubin levels in adult mice by re-administering an AAV8 vector.

PMID- 29448837
TI  - Restoring tracheal defects in a rabbit model with tissue engineered patches based
      on TGF-beta3-encapsulating electrospun poly(l-lactic acid-co-epsilon
      caprolactone)/collagen scaffolds.
AB  - Long segment tracheal stenosis often has a poor prognosis due to the limited
      availability of materials for tracheal reconstruction. Tissue engineered tracheal
      patches based on electrospun scaffolds and stem cells present ideal solutions to
      this medical challenge. However, the established engineering process is
      inefficient and time-consuming. In our research, to optimize the engineering
      process, core-shell nanofilms encapsulating TGF-beta3 were fabricated as
      scaffolds for tracheal patches. The morphological and mechanical characteristics,
      degradation and biocompatibility of poly(l-lactic acid-co-epsilon
      caprolactone)/collagen (PLCL/collagen) scaffolds with different compositions
      (PLCL:collagen 75:25, 50:50 and 25:75, respectively) were comparatively evaluated
      to determine the preferable compositional ratio. Then the chondrogenesis-inducing
      potential is investigated, and tracheal patches based on electrospun scaffolds
      and bone marrow mesenchymal stem cells (BMSCs) were constructed to restore
      tracheal defects in rabbit models. The results indicated that core-shell
      scaffolds with a PLCL/collagen proportion of 75:25 were eligible for tracheal
      patches. The stable and sustained release of TGF-beta3 from scaffolds could
      efficiently promote the chondrogenic differentiation of BMSCs and shorten the
      incubation time. Tracheal integrity was well maintained for 2 months after
      restoration; meanwhile, re-epithelialization also achieved. In conclusion, TGF
      beta3-encapsulating core-shell electrospun scaffolds with a PLCL/collagen
      proportion of 75:25 could be used to optimize engineering process of tracheal
      patches.

PMID- 29448838
TI  - Novel methotrexate soft nanocarrier/fractional erbium YAG laser combination for
      clinical treatment of plaque psoriasis.
AB  - Psoriasis is a commonly encountered chronic dermatological disease, presenting
      with inflammatory symptoms in patients. Systemic treatment of psoriasis is
      associated with several adverse effects, therefore the development of a
      customized topical treatment modality for psoriasis would be an interesting
      alternative to systemic delivery. The therapeutic modality explored in this
      article was the comparative treatment of psoriatic patients using
      nanoparticulated methotrexate in the form of jojoba oil-based microemulsion with
      or without fractional erbium YAG laser. Assessment parameters included follow-up
      photography for up to 8 weeks of treatment, estimation of the psoriasis severity
      [TES (thickness, erythema, scales)] score, and histopathological skin evaluation.
      The prepared methotrexate microemulsion was clinically beneficial and safe in
      treatment of psoriasis vulgaris. The concomitant use of the fractional laser
      provided improvement in the psoriatic plaques within shorter time duration (3
      weeks compared to 8 weeks of treatment), presenting an alternative topical
      treatment modality for psoriasis vulgaris.

PMID- 29448839
TI  - Role of growth factors and biomaterials in wound healing.
AB  - Wound healing is a biological complex process that involves several cell types
      under the control and regulation of several growth factors and cytokines. There
      have been efforts to study the therapeutic effects of granulocyte-macrophage
      colony-stimulating factor, platelet-derived growth factor, transforming growth
      factor-beta, vascular endothelial growth factor and basic fibroblast growth
      factor on chronic wounds. In addition, the effects of biomaterials such as nano
      fibrous chitin and chitosan have been proven to be effective on wound healing.
      Furthermore, stem cell therapy using adipose-derived stem cells (ASCs) has been
      developed as a new therapeutic method for wound repair and healing. In this
      review, we will summarize the role of stem cells; growth factors and biomaterials
      in wound healing and repair.

PMID- 29448840
TI  - Inverse association between serum albumin and future risk of venous
      thromboembolism: interrelationship with high sensitivity C-reactive protein.
AB  - PURPOSE: We aimed to assess the prospective association of serum albumin with
      venous thromboembolism (VTE) risk and evaluate if the association is independent
      of or modified by inflammation, as measured by high sensitivity C-reactive
      protein (hsCRP). DESIGN: We analysed data of 2176 men aged 42-61 years free from
      VTE in the Kuopio Ischemic Heart Disease study, with serum albumin concentrations
      measured at baseline using Coulter's bromocresol purple colorimetric assays.
      Hazard ratios (HRs) (95% confidence intervals [CI]) were calculated for VTE.
      RESULTS: There were 109 validated cases of VTE recorded during a median follow-up
      of 24.9 years. The risk of VTE increased linearly below a serum albumin
      concentration of ~48 g/l. In Cox regression analysis adjusted for established
      risk factors and other potential confounders, the HR (95% CI) for VTE per 1
      standard deviation lower serum albumin was 1.23 (1.02-1.47). The association
      remained persistent on further adjustment for hsCRP 1.22 (1.01-1.46).
      Furthermore, the association was not modified by hsCRP and persisted on exclusion
      of men with elevated hsCRP levels. CONCLUSIONS: In middle-aged Caucasian men, low
      serum albumin is associated with an increased risk of VTE, consistent with a
      linear dose-response relationship. The association is independent of and not
      modified by inflammation. Key messages   * Serum albumin may be associated with
      future risk of venous thromboembolism (VTE); however, the shape, nature,
      magnitude and consistency of the association is uncertain.   * In a population
      based prospective cohort study, low serum albumin was associated with an
      increased risk of VTE in a linear dose-response manner and this association was
      independent of and not modified by inflammation.   * Serum albumin concentrations
      may play a role in the development of VTE.

PMID- 29448841
TI  - The Association of Serum Iron-Binding Proteins and the Antioxidant Parameter
      Levels in Age-Related Macular Degeneration.
AB  - PURPOSE: Age-related macular degeneration (AMD) is the leading cause of the
      irreversible central visual loss among the elderly in the developed countries.
      Iron is considered a potent generator of the oxidative damage whose levels
      increase with age, potentially exacerbating the age-related diseases. The aim of
      this study was to assess the serum values of iron, and iron-binding proteins
      (transferrin, ferritin, and haptoglobin) in patients with AMD along with the
      parameters of the antioxidant defense: superoxide dismutase (SOD), glutathione
      peroxidase (GPx), glutathione reductase, and total antioxidant status (TAS), in
      order to analyze the possible impact of iron and iron-binding proteins to the
      development of oxidative stress in AMD patients, and the association of the
      selected parameters with the AMD. In addition, the aim was to examine the gender
      differences and calculate the cutoff points of tested parameters that could be
      associated with AMD. MATERIAL AND METHODS: A cross-sectional study included 55
      AMD patients aged 71.7 +/- 7.36 years and 65 aged-matched control subjects aged
      70.25 +/- 6.46 years. RESULTS: Significantly lower ferritin (P = 0.025), SOD (P =
      0.026), GPx (P = 0.019), and TAS (P < 0.004) values were found in patients with
      AMD compared to the controls (P < 0.05). Significant association of GPx < 27
      U/gHb (odds ratio [OR]: 1.13; 95% confidence interval [CI] 0.78-2.10; P = 0.049),
      TAS < 1.25 mmol/L (OR: 5.77; 95% CI 0.98-367.0; P < 0.000), ferritin < 84.8 pg/mL
      (OR: 2.52; 95% CI 1.37-4.62; P = 0.002), and haptoglobin<1.51 g/L (OR: 1.94; 95%
      CI 1.05-3.56; P = 0.031) was found with the AMD. According to receiver operating
      characteristic curve analysis, ferritin concentration <84.8 pg/L, GPx < 27 U/gHb,
      and TAS < 1.25 mmol/L have sufficient predictive ability for AMD. CONCLUSION:
      Significantly reduced capacity of the antioxidant defense system and iron-binding
      storage proteins (ferritin) found in AMD could have an important role in the
      development of increase oxidative stress in AMD patients.

PMID- 29448842
TI  - Knockdown of NRAGE induces odontogenic differentiation by activating NF-kappaB
      signaling in mouse odontoblast-like cells.
AB  - PURPOSE: Neurotrophin receptor-interacting MAGE homologue (Nrage) plays an
      important role in bone development and the metabolism of normal skeletal
      structures. Our previous study showed that Nrage inhibited the odontogenic
      differentiation of mouse dental pulp cells. However, the potential roles and
      mechanism of Nrage in regulating odontogenic differentiation are unknown. The aim
      of this study was to investigate the molecular mechanism of Nrage in odontogenic
      differentiation of mouse odontoblast-like cells. MATERIALS AND METHODS:
      Endogenous expression of Nrage was stably downregulated by lentivirus-mediated
      shRNA. Mineralized nodules formation was detected by alizarin red S staining. Dmp
      1, Dspp, and ALP mRNA and protein levels were detected by qRT-PCR and western
      blotting, respectively. In addition, ALPase activity was detected. Confocal
      microscopy and co-immunoprecipitation (co-IP) were used to analyze the
      interactions between NRAGE and NF-kappaB signaling molecules. An IKK inhibitor
      was also used in the study. RESULTS: NRAGE expression in odontoblasts was
      downregulated during mouse first maxillary molar development. Moreover, NRAGE
      expression was downregulated during odontogenic differentiation of odontoblast
      like cells. NRAGE knockdown significantly upregulated DMP1 and DSP expression,
      increased ALPase activity, and promoted mineralized nodule formation. In
      addition, NRAGE knockdown increased the translocation of NF-kappaB1 to the
      nucleus and phosphorylation levels of p65. Co-IP results showed that NRAGE bound
      to IKKbeta. Most importantly, the promoting effect of Nrage knockdown on
      odontoblastic differentiation was reduced after treatment with an IKK inhibitor.
      CONCLUSIONS: Our data confirmed that NRAGE is an important regulator of
      odontogenic differentiation of odontoblasts by inhibiting the NF-kappaB signaling
      pathway through binding to IKKbeta. ABBREVIATIONS: Nrage: neurotrophin receptor
      interacting MAGE homologue; DSP: dentin sialophospho protein; DMP-1: dentin
      matrix protein-1; BMP: bone morphogenetic protein; Wnt: wingless; NF-kappaB:
      nuclear factor of activated B cells; DAPI: 4',6-diamidino-2-phenylindole; KO:
      knockout; DPCs: dental pulp cells; AA: ascorbic acid; beta-Gly: beta
      glycerophosphate; Dex: dexamethasone; co-IP: co-immunoprecipitation; IkappaB:
      inhibitor of NF-kappaB; IKK: IkappaB kinase.

PMID- 29448844
TI  - Corrigendum.

PMID- 29448843
TI  - Cenicriviroc for the treatment of non-alcoholic steatohepatitis and liver
      fibrosis.
AB  - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) has an increasing
      prevalence worldwide. At present, no specific pharmacotherapy is approved for
      NAFLD. Simple steatosis and nonalcoholic steatohepatitis (NASH) can progress to
      liver fibrosis that is associated with mortality in NAFLD. The recruitment of
      inflammatory monocytes and macrophages via chemokine receptor CCR2 as well as of
      lymphocytes and hepatic stellate cells via CCR5 promote the progression of NASH
      to fibrosis. Areas covered: I summarize preclinical and clinical data on the
      efficacy and safety of the dual CCR2/CCR5 inhibitor cenicriviroc (CVC, also TBR
      652 or TAK-652) for the treatment of NASH and fibrosis. In animal models of liver
      diseases, CVC potently inhibits macrophage accumulation in the liver and
      ameliorates fibrosis. In a phase 2b clinical trial (CENTAUR) on 289 patients with
      NASH and fibrosis, CVC consistently demonstrated liver fibrosis improvement after
      1 year of therapy and had an excellent safety profile, leading to the
      implementation of a phase 3 trial (AURORA). Expert opinion: Preclinical and
      clinical data support the development of CVC as a safe and potent antifibrotic
      agent. However, open questions around CVC are the durability of antifibrotic
      responses, divergent effects on NASH versus fibrosis, potential long-term
      concerns and the expected path to approval.

PMID- 29448845
TI  - A systematic review of economic evaluations of tyrosine kinase inhibitors of
      vascular endothelial growth factor receptors, mammalian target of rapamycin
      inhibitors and programmed death-1 inhibitors in metastatic renal cell cancer.
AB  - INTRODUCTION: The therapeutic categories of tyrosine kinase inhibitors of
      vascular endothelial growth factor receptors, mammalian target of rapamycin
      inhibitors and programmed death-1 inhibitors have transformed the treatment of
      metastatic renal cell cancer. Nevertheless, this comes at an increased cost, in
      tandem with similar fiscal pressures in the broader oncology sector, which may
      jeopardize the sustainability of health systems. Areas covered: To this
      direction, the economic evaluation of these agents is essential for rational and
      efficient decision-making and resource allocation process. The aim of this study
      is to glean, assess and present an outline of the available cost-effectiveness
      studies of these agents in the management of metastatic renal cell cancer. Expert
      Commentary: We concluded that the results of the economic evaluations are
      pertinent, apart from the product under evaluation, to the country setting as
      well.

PMID- 29448846
TI  - Are infectious diseases and microbiology new fields for thermal therapy research?
AB  - Antimicrobial chemotherapy and surgery are classical methods for treating
      infectious diseases. However, there is a need for alternative methods to cure
      infections caused by antibiotic-resistant pathogens, recurrent or chronic
      infections, and unreachable local infections in which the use of drugs or surgery
      is anatomically and physically restricted. Several micro-organisms are known to
      be sensitive to mild hyperthermia, and this sensitivity is one of the potential
      benefits proposed for the host during an episode of fever. Additionally, some
      immunological or biophysical changes occur during hyperthermia. These changes may
      be useful for eliminating thermo-susceptible microbial pathogens using local heat
      therapy. There are several experimental studies proposing the use of hyperthermia
      to treat local infections. The infected organs or tissues may be heated up to a
      temperature that can inhibit invading microorganisms. Here, it is hypothesised
      that local heat therapy may become an alternative or adjuvant method for curing
      local infections. Here, we highlight the potential for local hyperthermia in the
      treatment of bacterial infections caused by thermo-susceptible pathogens in a
      systematic plan. If the proposed thermal-microbiology concepts and local thermal
      therapies can be adapted to clinical microbiology and infectiology, new medical
      fields, such as thermo-microbiology and thermo-infectiology, may be created in
      the future.

PMID- 29448847
TI  - Effect of early cumulus cells removal and early rescue ICSI on pregnancy outcomes
      in high-risk patients of fertilization failure.
AB  - OBJECTIVE: The objective of this retrospective study was to evaluate clinical
      outcomes of early cumulus cells removal and early rescue intracytoplasmic sperm
      injection (ICSI) in high-risk patients of fertilization failure during human in
      vitro fertilization (IVF). METHODS: A total of 5,518 patients were enrolled
      between January 2014 to December 2016. Of which 505 couples performed short
      insemination with >30% fertilization rate were included in short-term IVF group,
      102 patients detected total fertilization failure (TFF) were treated with early
      rescue ICSI (R-ICSI group), and 4911 couples underwent conventional IVF with
      overnight co-incubation of gametes (traditional IVF group). The clinical outcomes
      were analyzed among the three groups. RESULTS: The embryo implantation rates
      (40.34%, 39.78% and 42.42% for traditional, short-term IVF and R-ICSI groups,
      respectively) were comparable in the three groups. The clinical pregnancy rates
      among traditional IVF group, short-term IVF group and R-ICSI group were 57.95%,
      57.03% and 60.78%, respectively, and the difference among three groups didn't
      reach significance. CONCLUSION: The present study indicated that short
      insemination had no detrimental effects on clinical outcomes in human IVF and
      could prevent the occurrence of TFF combined with early rescue ICSI for high-risk
      patients of fertilization failure, which attained acceptable pregnancy outcomes.

PMID- 29448848
TI  - Development and characterization of morin hydrate-loaded micellar nanocarriers
      for the effective management of Alzheimer's disease.
AB  - The aim of this study was to prepare and characterise oral delivery of morin
      hydrate-loaded micellar nanocarriers using Pluronic P127 and Pluronic F123 for
      the effective management of Alzheimer's disease. After administration of
      formulation brain and blood drug concentration were found to be highest for
      optimised morin hydrate-loaded micellar nanocarriers as compared to plain morin
      hydrate. Significant (p < 0.05) reduction in assessed pharmacodynamic parameters
      was observed after administration of morin hydrate-loaded micellar nanocarriers
      as compared to disease control group. Chronic treatment with morin-loaded
      micelles significantly increased the memory in AlCl3 induced Alzheimer's disease
      in Wistar rats.

PMID- 29448849
TI  - Development of small-molecule immune checkpoint inhibitors of PD-1/PD-L1 as a new
      therapeutic strategy for tumour immunotherapy.
AB  - Cancer immunotherapy has been increasingly utilised to treat advanced
      malignancies. The signalling network of immune checkpoints has attracted
      considerable attention. Immune checkpoint inhibitors are revolutionising the
      treatment options and expectations for patients with cancer. The reported
      clinical success of targeting the T-cell immune checkpoint receptors PD-1/PD-L1
      has demonstrated the importance of immune modulation. Indeed, antibodies binding
      to PD-1 or PD-L1 have shown remarkable efficacy. However, antibody drugs have
      many disadvantages, such as their production cost, stability, and immunogenicity
      and, therefore, small-molecule inhibitors of PD-1 and its ligand PD-L1 are being
      introduced. Small-molecule inhibitors could offer inherent advantages in terms of
      pharmacokinetics and druggability, thereby providing additional methods for
      cancer treatment and achieving better therapeutic effects. In this review, we
      first discuss how PD-1/PD-L1-targeting inhibitors modulate the relationship
      between immune cells and tumour cells in tumour immunotherapy. Second, we discuss
      how the immunomodulatory potential of these inhibitors can be exploited via
      rational combinations with immunotherapy and targeted therapy. Third, this review
      is the first to summarise the current clinical and preclinical evidence regarding
      small-molecule inhibitors of the PD-1/PD-L1 immune checkpoint, considering
      features and responses related to the tumours and to the host immune system.

PMID- 29448850
TI  - Treatment changes in patients with psoriasis on etanercept or adalimumab: a
      retrospective chart review.

PMID- 29448851
TI  - Salvage tigecycline in high risk febrile neutropenic patients with hematological
      malignancies: a prospective multicenter study.
AB  - The purpose of this prospective, multi-center study was to examine the efficacy
      and safety of tigecycline as empirical treatment in neutropenic patients with
      hematological malignancies who failed to respond to first-line antibiotics. A
      total of 125 patients with persistent fever (>72 h) despite first-line
      antibiotics received empirical treatment with tigecycline (loading dose of 100
      mg, followed by 50 mg every 12 h). The use of other antimicrobial agents was not
      restricted. Treatment success rate was 68.0%. Subgroup analysis revealed a
      success rate of 73.1% in patients with pneumonia and 35.3% in patients with
      bacteremia. Toxicities were moderate with gastrointestinal symptoms being the
      main side effects. In conclusion, tigecycline-based antibacterial regimen was a
      justifiable empirical treatment in febrile neutropenic patients who failed to
      respond to first-line antibiotics except those with bacteremia. For patients with
      bacteremia, trials on higher-dose of tigecycline are needed.

PMID- 29448852
TI  - Memantine in Japanese patients with moderate to severe Alzheimer's disease: meta
      analysis of multiple-index responder analyses.
AB  - BACKGROUND: Responder analyses assessing clinical worsening have attempted to
      clarify clinically meaningful drug efficacy enhancements in patients with
      Alzheimer's disease (AD). RESEARCH DESIGN AND METHODS: This was a meta-analysis
      of two multicenter, randomized, double-blind, parallel-group, 24-week studies of
      633 Japanese patients with moderate to severe AD receiving memantine 20 mg/day (n
      = 318) or placebo (n = 315). The clinical trial registration number is
      UMIN000026013. RESULTS: Overall odds ratios (OR) for a reduced likelihood of
      clinical worsening (memantine versus placebo) were statistically significant on
      the following individual and combined rating scales: Severe Impairment Battery
      Japanese version (SIB-J, OR 0.52; 95% CI: 0.37, 0.73; p = 0.0001); Behavioral
      Pathology in AD Rating Scale (BEHAVE-AD, OR 0.53; 95% CI: 0.37, 0.75; p =
      0.0003); and SIB-J + Clinician's Interview-Based Impression of Change-plus
      Japanese version (SIB-J + CIBIC-plus-J; OR 0.53; 95% CI: 0.37, 0.77; p = 0.0009).
      A significantly reduced risk of triple worsening was evident in the memantine
      versus placebo group on the combined SIB-J + CIBIC-plus-J + BEHAVE-AD rating
      scales (OR 0.38; 95% CI: 0.22, 0.65; p = 0.0003). CONCLUSIONS: Memantine is a
      viable treatment option for patients with AD presenting not only with cognitive
      impairment, but also with a broader range of symptoms, including the behavioral
      and psychological symptoms of dementia.

PMID- 29448853
TI  - Risk factors for positive margins after wide local excision of cutaneous squamous
      cell carcinoma.
AB  - BACKGROUND AND OBJECTIVES: The standard treatment for cutaneous squamous cell
      carcinoma (cSCC) is wide local excision (WLE). Incomplete tumor excision is
      associated with increased recurrence rates and mortality risk. Risk factors for
      positive margins after WLE of cSCC has been examined in only a few studies. We
      sought to assess the influence of several clinicopathological factors on margin
      status in the largest cSCC population to date. METHODS: We performed a
      retrospective review of records at two skin cancer clinics identifying patients
      with biopsy-proven cSCC who underwent WLE. We mined clinicopathological
      information for eligible subjects including age, gender, lesion location,
      immunosuppression, previous treatment, lesion size, biopsy type, tumor subtype,
      tumor thickness, degree of differentiation, ulceration and perineural invasion.
      RESULTS: A total of 1468 patients were eligible and 117 (8%) had positive margins
      after WLE. Older age at diagnosis (p = .011), lesion location on the head and
      neck (p < .001), previous treatment (p < .001), increased lesion diameter (p <
      .001), invasive subtype (p = .020) or increased tumor thickness (p < .001) were
      statistically significant risk factors for positive surgical margins.
      CONCLUSIONS: Our results present an opportunity to stratify cSCC patients into
      low- or high-risk for incomplete tumor clearance after WLE based on several
      clinicopathological factors. These findings should educate and inform the
      dermatologic surgeon's choice of primary management of cSCC.

PMID- 29448854
TI  - Mental health care providers talk about their experiences preventing suicide in
      people with substance use disorders in South Africa: implications for clinical
      practice.
AB  - OBJECTIVE: This study explored mental health care providers' experiences of
      preventing suicide in people with substance use disorders and their perceptions
      of factors related to clinical practice that contributed to these experiences.
      METHODS: In-depth, semistructured interviews were conducted with 18 mental health
      care providers working in South Africa. Thematic analysis was used to analyse the
      data inductively with Atlas.ti software. RESULTS: Participants described feeling
      hopeless, helpless, powerless and guilty and needed to debrief from their
      experiences of preventing suicide. They perceived their experiences to be related
      to the difficulties of treating substance use disorders, the difficulties of
      assessing and managing suicide risk and how treating substance use might increase
      suicide risk. CONCLUSIONS: The ways in which mental health care providers think
      about suicide and make sense of their experiences affects their perceived
      abilities to prevent suicide. Educating mental health care providers to transcend
      the limitations of risk factor approaches to suicide prevention and utilise
      evidence-based strategies for treating substance use disorders and associated
      problems, may be important to empower them and make them feel competent in
      suicide prevention. Empowering people with substance use disorders may help
      prevent suicide and may require collaboration between mental health care
      providers and allied professionals.

PMID- 29448855
TI  - Acute effects of blood flow restriction on exercise-induced free radical
      production in young and healthy subjects.
AB  - The main purpose of this study was to investigate the acute local and systemic
      effects of low-load resistance exercise (30% 1RM) with partial vascular occlusion
      on exercise-induced free radical production and to compare these effects with
      other established training methods. Fifteen young and healthy males (25 +/- 3
      years) performed the following four sessions in a counterbalanced order on
      separate days: low-load resistance exercise (LI: 30% 1RM), low-load resistance
      exercise with blood flow restriction (LIBR: 30% 1RM), high-load resistance
      exercise (HI: 80% 1RM) and an additional session without exercise but blood flow
      restriction only (BR). Blood samples were obtained 15 min prior to and
      immediately after exercise sessions from the right index finger and first toe. To
      analyze concentrations of reactive oxygen species (ROS), electron paramagnetic
      resonance (EPR) spectroscopy was used. Additionally, mitochondrial ROS production
      was measured by adding inhibitors of electron transport chain complex III. There
      was an increased systemic ROS generation after the LIBR session from 0.837 +/-
      0.093 to 0.911 +/- 0.099 umol/l/min. However, no local or systemic time *
      condition interaction was detected for ROS production. Regarding mitochondrial
      ROS production, results were not different between the conditions. Although the
      low-load resistance exercise session with partial vascular occlusion elicited
      systemic increases of ROS production, no significant changes were seen on a local
      level. We assume that this ROS concentration might not be high enough to induce
      cellular damage but is rather involved in muscle remodulation. However, this
      needs to be confirmed by future research.

PMID- 29448856
TI  - Study of target and non-target interplay in spatial attention task.
AB  - Selective visual attention is the ability to selectively pay attention to the
      targets while inhibiting the distractors. This paper aims to study the targets
      and non-targets interplay in spatial attention task while subject attends to the
      target object present in one visual hemifield and ignores the distractor present
      in another visual hemifield. This paper performs the averaged evoked response
      potential (ERP) analysis and time-frequency analysis. ERP analysis agrees to the
      left hemisphere superiority over late potentials for the targets present in right
      visual hemifield. Time-frequency analysis performed suggests two parameters i.e.
      event-related spectral perturbation (ERSP) and inter-trial coherence (ITC). These
      parameters show the same properties for the target present in either of the
      visual hemifields but show the difference while comparing the activity
      corresponding to the targets and non-targets. In this way, this study helps to
      visualise the difference between targets present in the left and right visual
      hemifields and, also the targets and non-targets present in the left and right
      visual hemifields. These results could be utilised to monitor subjects'
      performance in brain-computer interface (BCI) and neurorehabilitation.

PMID- 29448857
TI  - Therapy-free remission in chronic myeloid leukemia: possible mechanism.

PMID- 29448858
TI  - Long-term results of the AIEOP MH'96 childhood Hodgkin's lymphoma trial and focus
      on significance of response to chemotherapy and its implication in low risk
      patients to avoid radiotherapy.
AB  - Identify a subset of early-stage HL children (GR1) curable with limited
      chemotherapy+/-radiotherapy; improve outcome of intermediate (GR2) and high-risk
      (GR3) patients; establish impact of response to chemotherapy evaluated with
      conventional imaging (CI). One hundred and sixty GR1-patients received 3ABVD +
      involved-field (IF) low-dose (LD) (20 Gy) irradiation if mediastinal mass or
      partial response (PR) after chemotherapy. Eighty-five GR2- and 315 GR3-patients
      received 4 and 6 COPP/ABV + IFRT, respectively. The 63 GR1 patients spared from
      radiotherapy had 15-year survival and EFS of 100 and 84.5%, respectively. The GR2
      and GR3 15-year FFP were 84.7 and 78.6%, respectively. No different prognosis for
      patients in CR or PR evaluated during and after chemotherapy was observed. In
      conclusion, low-risk patients in CR may be successfully treated with radiation
      free, low-intensity chemotherapy. Good, but less satisfactory, results were
      registered in GR2 and GR3. Response evaluated with CI is not a prognostic factor,
      but permits identification of low-risk patients who can avoid radiotherapy.

PMID- 29448859
TI  - Assessment of the external validity of the American Joint Committee on Cancer 8th
      staging system for anal carcinoma.
AB  - BACKGROUND: The current study evaluates the prognostic value of the 8th edition
      of the American Joint Committee on Cancer (AJCC) staging system for patients with
      anal carcinoma. PATIENTS AND METHODS: The Surveillance, Epidemiology and End
      Results (SEER) database (2004-2014) was explored and AJCC 6th and 8th stages were
      formulated. Through Kaplan-Meier analysis, overall survival analyses were
      performed. The Cox regression model (adjusted for age, gender, histology,
      ethnicity, subsite and grade) was calculated for cancer-specific survival and,
      subsequently, pairwise comparisons of hazard ratios were calculated. RESULTS: A
      total of 11,934 anal carcinoma patients were included in the analysis. Overall
      survival was compared according to both AJCC 6th and 8th systems. For both
      staging systems, the p value for the trend in overall survival was significant (p
      < .0001). Nevertheless, for the AJCC 6th system, stage IIIA and IIIB curves were
      overlapping; while for the AJCC 8th system, the median survival for stage IIB was
      lower than the mean survival for stage IIIA (74 months vs. 96 months). Moreover,
      stage IIIB and stage IIIC curves were overlapping. The cause-specific (cancer
      specific) Cox regression hazard was calculated for both staging systems. Pairwise
      hazard ratio comparisons between different AJCC 6th stages were performed and all
      p values for comparisons were significant (p < .05). Pairwise hazard ratio
      comparisons between different AJCC 8th stages were performed and only the
      following comparisons were significant (p < .0001) (I vs. IIA; IIA vs. IIB; IIIC
      vs. IV). The C-statistic (using death from anal carcinoma as the dependent
      variable) for the AJCC 6th staging system was: 0.681 (SE: 0.009; 95% CI: 0.664
      0.698); while the C-statistic for the AJCC 8th staging system was 0.687 (SE:
      0.008; 95% CI: 0.670-0.703). CONCLUSIONS: There is no evidence of significant
      improvement in the AJCC 8th edition compared to AJCC 6th (or 7th) edition in
      terms of overall or cancer-specific survival prediction.

PMID- 29448860
TI  - Therapeutic ionizing radiation induced bone loss: a review of in vivo and in
      vitro findings.
AB  - Radiation therapy is one of the routine treatment modalities for cancer patients.
      Ionizing radiation (IR) can induce bone loss, and consequently increases the risk
      of fractures with delayed and nonunion of the bone in the cancer patients who
      receive radiotherapy. The orchestrated bone remodeling can be disrupted due to
      the affected behaviors of bone cells, including bone mesenchymal stem cells
      (BMSCs), osteoblasts and osteoclasts. BMSCs and osteoblasts are relatively
      radioresistant compared with osteoclasts and its progenitors. Owing to different
      radiosensitivities of bone cells, unbalanced bone remodeling caused by IR is
      closely associated with the dose absorbed. For doses less than 2 Gy,
      osteoclastogenesis and adipogenesis by BMSCs are enhanced, while there are
      limited effects on osteoblasts. High doses (>10 Gy) induce disrupted architecture
      of bone, which is usually related to decreased osteogenic potential. In this
      review, studies elucidating the biological effects of IR on bone cells (BMSCs,
      osteoblasts and osteoclasts) are summarized. Several potential preventions and
      therapies are also proposed.

PMID- 29448861
TI  - Self-retaining barbed suture reduces warm ischemia time during laparoscopic
      partial nephrectomy.
AB  - OBJECTIVE: To evaluate the efficacy and safety of self-retaining barbed suture in
      renorrhaphy during laparoscopic partial nephrectomy by comparing surgical
      outcomes in a prospective randomized manner. MATERIAL AND METHODS: From July 2014
      to July 2015, a total of 60 patients with T1 renal tumor were randomized into two
      equal groups: self-retaining barbed suture (SRBS) and conventional absorbable
      polyglactin suture (non-SRBS group). All patients were treated by retroperitoneal
      laparoscopic partial nephrectomy. One surgeon with high volume experience
      performed all procedures. The patient demographics and perioperative outcomes
      were compared. RESULTS: The patient demographics and tumor characteristics were
      comparable. The mean tumor size and R.E.N.A.L. scores were comparable between the
      two groups. LPN was successfully accomplished in all patients without open
      conversion. The warm ischemia and renorrhaphy times were significantly shorter in
      the SRBS group (18.8 +/- 8.2 vs. 22.9 +/- 7.3 min, P = .04; 10.4 +/- 3.7 vs. 13.8
      +/- 5.6 min, P = .01). The minor complication rate was 13.3% vs. 10.0%, which was
      comparable. No major complication occurred. CONCLUSIONS: The randomized
      controlled trial demonstrates that SRBS for renorrhaphy during retroperitoneal
      laparoscopic partial nephrectomy is safe and efficient. Application of barbed
      suture simplifies the parenchymal repair procedure and reduces warm ischemia time
      in comparison with conventional suture.

PMID- 29448862
TI  - Filgotinib for the treatment of Crohn's disease.
AB  - INTRODUCTION: Inflammatory bowel diseases, such as Crohn's disease (CD) and
      ulcerative colitis (UC), are widespread diseases (with an estimated 2.2 million
      Europeans affected), and even populations previously considered 'low risk' (such
      as Japan and India) are witnessing an increasing incidence. CD is a chronic,
      progressive immunologically driven disease, with an evolution characterized by
      succession of periods of progression and remission. New physiopathological
      pathways are continuously being discovered, the more we understand about how the
      disease appears and progresses, the more targets become available for the
      development of novel therapies. Areas covered: Filgotinib is one of these
      promising new therapies; this article discusses the currently available data. We
      used an exhaustive search of the PubMed database to corroborate information
      regarding its chemical characteristics, and the studies evaluating clinical
      efficacy and safety. Expert opinion: Up to now, the phase-II study evaluating
      Filgotinib yielded very promising results in moderate to severe CD patients, with
      good clinical response, mucosal healing, while having few and moderate adverse
      effects, both in anti-TNF naive and resistant patients. Phase-III studies are
      still ongoing and will help decide whether Filgotinib will be a worthwhile drug
      in the treatment of CD and the best way to use it.

PMID- 29448863
TI  - Mental health literacy, sub-clinical personality disorders and job fit.
AB  - BACKGROUND: This study looked at lay theories of how people with sub-clinical
      personality disorders experience the world of work. AIMS: The aim was to
      investigate the paradox that subclinical and clinical personality disorders are
      seen as beneficial for success, rather than a handicap in certain jobs. METHODS:
      In all, 230 participants read 14 vignettes derived from Oldham and Morris's book
      describing DSMIII personality disorders for a popular audience. Participants were
      invited to suggest what type of work each disordered person may be successful at,
      as well as six ratings of their social adjustment. RESULTS: There was a tendency
      for people to believe those with OCD to be suited to Accountancy, Narcissism and
      Paranoia to General Management, Histrionic PD to being an Actor and Schizotypal
      an Artist. Surprisingly Paranoid and Sadistic people were judged to be good
      managers and Histrionic, Passive Aggressive and Schizotypal the worst. People in
      Cluster C were judged as best managers, but those in Cluster B as better
      adjusted. CONCLUSIONS: Results show that lay people believe that certain "dark
      side" traits associated with personality disorders, particularly dependency and
      OCD, are thought to be beneficial for success, rather than failure, in many jobs.

PMID- 29448864
TI  - Development of a novel 6-DOF parallel mechanism moving platform for investigating
      the effects of multimodal sensory feedback information regarding postural
      stability in humans.
AB  - The purpose of this study was to develop a six-degree-of-freedom parallel
      mechanism moving platform to investigate the effects of multimodal sensory
      feedback information while standing upright. We constructed a custom-designed
      disturbance-applying instrument (DAI) consisting of a support surface suspended
      from eight pneumatic artificial muscles. The posture of the support surface was
      controlled with a proportional-integral-derivative (PID) feedback system using an
      infra-red camera-based real-time 3D motion capture system, and was estimated by
      step and frequency responses. Head trajectories of two healthy subjects were
      recorded to evaluate the effect of the differences in the impedance of the
      support surface during upright standing with their eyes opened/closed. The
      results demonstrated that the step and frequency responses of the DAI were good
      enough to enhance the bodily oscillation and head motion relative to the support
      surface. Indeed, the head-swaying space, using the DAI in a 0.2-Hz air-supplying
      condition during upright standing with their eyes closed, was larger than in the
      other standing condition. These results suggest that the specific medio-lateral
      head swaying was caused by the effects of the multimodal sensory feedback
      information using the DAI. In conclusion, we developed a novel moving platform to
      investigate the effects of multimodal sensory feedback information upon upright
      postural control. The DAI would be particularly valuable to enhance the head
      swaying space during upright standing by changing the impedance of the support
      surface or stimulating the translational and/or rotational sensory feedback
      integration.

PMID- 29448865
TI  - Diagnostic accuracy of three screening questions (3Q/TMD) in relation to the
      DC/TMD in a specialized orofacial pain clinic.
AB  - OBJECTIVE: To determine the diagnostic accuracy of three screening questions
      (3Q/TMD) in relation to the Diagnostic Criteria for Temporomandibular Disorders
      (DC/TMD), in a specialized clinic. MATERIAL AND METHODS: Consecutive patients,
      >18 years, referred with a possible TMD complaint to the Orofacial Pain and
      Dysfunction clinic, Academic Centre for Dentistry Amsterdam, the Netherlands,
      were included in the study. All patients (n = 449; mean age 44 years; 72%
      females), answered the 3Q/TMD and the DC/TMD questionnaire before a DC/TMD
      examination. The 3Q/TMD constitutes of two questions on weekly pain from the jaw,
      face and temple region (Q1), and on function (Q2), and one function-related
      question on weekly catching and/or locking of the jaw (Q3). Q1 and Q2 were
      evaluated in relation to a DC/TMD pain diagnosis and Q3 in relation to a subgroup
      of DC/TMD intra-articular diagnosis, referred to as the reference standard.
      RESULTS: In total, 44% of patients received a pain-related DC/TMD diagnosis and
      33% an intra-articular reference DC/TMD diagnosis. Sensitivity for the two pain
      screening questions was high (0.83-0.94), whereas specificity was low (0.41
      0.55). For the function-related question, sensitivity was low (0.48), whereas
      specificity was high (0.96). CONCLUSIONS: In a specialized pain clinic, the two
      pain questions (Q1, Q2) are positive in most patients with pain-related TMD.
      Therefore, in case of a positive response, further diagnostic procedures for TMD
      pain are warranted. For the functional screening question (Q3), a positive
      response is indicative for an intra-articular DC/TMD diagnosis, while in case of
      a negative outcome, an intra-articular TMD might still be present.

PMID- 29448866
TI  - Multifunctional mesoporous silica nanoparticles as efficient transporters of
      doxorubicin and chlorin e6 for chemo-photodynamic combinatorial cancer therapy.
AB  - A multimodal nanocarrier based on mesoporous silica nanoparticles (MSNs) is
      developed to co-delivery photosensitizer chlorin e6 (Ce6) and chemotherapeutic
      agent doxorubicin (Dox) for cancer combination therapy. Ce6 was covalently
      conjugated with mesoporous silica nanoparticles, which could increase the loading
      efficiency, and allowed for photodynamic therapy. Doxorubicin was loaded into the
      pores of mesoporous silica nanoparticles to afford the dual drug delivery system
      Dox@MSNs-Ce6. These hybrid nanoparticles have an average diameter of about 100 nm
      and slightly negative charge of about -17 mV. The Dox@MSNs-Ce6 nanoparticles
      could efficiently enter into cancer cells. The cellular reactive oxygen species
      level in treated cells increased about 17 times, upon 660 nm light irradiation
      (10 mW/cm2, 2 min). More importantly, Dox@MSNs-Ce6 exhibited excellent
      synergistic effect through combining chemotherapy and photodynamic therapy
      against A549 lung cancer cells. Our work provides an effective strategy for
      anticancer drug delivery and combination therapy.

PMID- 29448867
TI  - Comparison of the knitted silk vascular grafts coated with fibroin sponges
      prepared using glycerin, poly(ethylene glycol diglycidyl ether) and poly(ethylene
      glycol) as porogens.
AB  - Development of a small-diameter artificial vascular graft is urgent because
      existing materials often occlude within a short time. We have shown that small
      diameter vascular graft using Bombyx mori silk fibroin is a potential candidate.
      Silk fibroin grafts are fabricated by coating silk fibroin on the knit tube
      prepared from silk fibroin fibers. However, there is a serious problem that the
      coated silk fibroin portion hardens when alcohol is used for insolubilization of
      the coated silk fibroin. This hardening prevents the desired biodegradation of
      the coated silk fibroin. In this study, we improved the silk fibroin coating
      method of the knit silk fibroin tube. Namely, the silk fibroin sponge coating was
      performed using glycerin, poly(ethylene glycol diglycidyl ether) or poly(ethylene
      glycol). In addition, silk fibroin grafts were prepared avoiding dryness during
      the coating process and were kept in the hydrated state until implantation into
      the abdominal aorta was complete. After implantation of the hydrated silk fibroin
      grafts, grafts were taken out at two weeks or three months, and histopathological
      examination was performed. The grafts coated with three types of silk fibroin
      sponges had a higher tissue infiltration rate than alcohol-treated grafts and
      were superior in the formation of smooth muscle cell and vascular endothelial
      cell remodeling. Biodegradations of the silk fibroin grafts prepared using the
      three types of silk fibroin sponge coatings and alcohol-treated silk fibroin
      grafts were also examined with protease XIV in vitro, and the grafts were
      observed by scanning electron microscopy before and 24 h after biodegradation.
      Faster biodegradations were observed for grafts coated with the three types of
      silk fibroin sponges. 13C solid-state nuclear magnetic resonance studies showed
      that the conformation of the silk fibroin sponge prepared using porogen was a
      random coil with high mobility in the hydrated state. We believe that small
      diameter silk fibroin vascular grafts coated with quick biodegradable silk
      fibroin sponges can be developed based on these findings.

PMID- 29448868
TI  - A Practical Approach to Including Adults Unable to Consent in Research.

PMID- 29448869
TI  - Development and validation of probe drug cocktails for the characterization of
      CYP450-mediated metabolism by human heart microsomes.
AB  - 1. The objective of our study was to develop and validate a cocktail approach to
      allow the simultaneous characterization of various CYP450-mediated oxidations by
      human heart microsomes for nine probe drug substrates, namely, 7-ethoxyresorufin,
      bupropion, repaglinide, tolbutamide, bufuralol, chlorzoxazone, ebastine,
      midazolam and dodecanoic acid. 2. The first validation step was conducted using
      recombinant human CYP450 isoenzymes by comparing activity measured for each probe
      drug as a function of (1) buffer used, (2) selectivity towards specific
      isoenzymes and (3) drug interactions between probes. Activity was all measured by
      validated LC-MSMS methods. 3. Two cocktails were then constituted with seven of
      the nine drugs and subjected to kinetic validation. Finally, all probe drugs were
      incubated with human heart microsomes prepared from ventricular tissues obtained
      from 12 patients undergoing cardiac transplantation. 4. Validated cocktail #1
      including bupropion, chlorzoxazone, ebastine and midazolam was used to
      characterize CYP2B6-, 2E1-, 2J2- and 3A5-mediated metabolism in human hearts. 5.
      Cocktail #2 which includes bufuralol, 7-ethoxyresorufin and repaglinide failed
      the validation step. Substrates in cocktail #2 as well as tolbutamide and
      dodecanoic acid had to be incubated separately because of their physico-chemical
      characteristics (solubility and ionization) or drug interactions. 6. Activity in
      HHM was the highest towards ebastine, chlorzoxazone and tolbutamide.

PMID- 29448870
TI  - A new assessment tool for ulnar drift in patients with rheumatoid arthritis using
      pathophysiological parameters of the metacarpophalangeal joint.
AB  - OBJECTIVES: To establish a new assessment tool for ulnar drift (UD) in rheumatoid
      arthritis (RA). METHODS: We established an observational cohort of 67 patients
      (134 rheumatoid hands) beginning in 2004. Fifty-two patients (100 hands) had
      follow-up in 2009 and 37 patients (63 hands) completed follow-up in 2015. UD was
      evaluated with the Fearnley classification and our scoring method, which assesses
      four parameters of the metacarpophalangeal joint. Cluster analysis using UD
      parameters divided hands into groups. Changes in UD over time, correlation of the
      Fearnley stage and cluster with a functional assessment, and reliability of the
      parameters were analyzed. RESULTS: UD increased and worsened over time according
      to the trend test. A dendrogram indicated five clusters would be appropriate.
      Both the Fearnley classification and cluster were associated with function;
      however, our method related to function more linearly (R-squared: 0.42). We found
      one type of hand in which bone destruction precedes the joint dislocation and one
      type in which joint dislocation progresses with little deviation during UD
      progression. CONCLUSION: Our UD evaluation appeared to be simple and related to
      function. Additionally, it enables dividing UD hands into five stages. Thus, our
      assessment should be beneficial compared to the Fearnley classification in
      considering treatments of UD.

PMID- 29448871
TI  - Interactions of organophosphorus pesticides with solute carrier (SLC) drug
      transporters.
AB  - 1. Organophosphorus pesticides (OPs) are known to interact with human ATP-binding
      cassette drug efflux pumps. The present study was designed to determine whether
      they can also target activities of human solute carrier (SLC) drug transporters.
      2. The interactions of 13 OPs with SLC transporters involved in drug disposition,
      such as organic cation transporters (OCTs), multidrug and toxin extrusion
      proteins (MATEs), organic anion transporters (OATs) and organic anion
      transporting polypeptides (OATPs), were mainly investigated using transporter
      overexpressing cell clones and fluorescent or radiolabeled reference substrates.
      3. With a cut-off value of at least 50% modulation of transporter activity by 100
      uM OPs, OAT1 and MATE2-K were not impacted, whereas OATP1B1 and MATE1 were
      inhibited by two and three OPs, respectively. OAT3 activity was similarly blocked
      by three OPs, and was additionally stimulated by one OP. Five OPs cis-stimulated
      OATP2B1 activity. Both OCT1 and OCT2 were inhibited by the same eight OPs,
      including fenamiphos and phosmet, with IC50 values however in the 3-30 uM range,
      likely not relevant to environmental exposure. 4. These data demonstrated that
      various OPs inhibit SLC drug transporter activities, especially those of OCT1 and
      OCT2, but only when used at high concentrations not expected to occur in
      environmentally-exposed humans.

PMID- 29448873
TI  - Comparison of Self-Reported and Behavioral Pain Assessment Tools in Critically
      Ill Patients.
AB  - BACKGROUND: Self-reported and behavioral pain assessment scales are often used
      interchangeably in critically ill patients due to fluctuations in mental status.
      The correlation between scales is not well elucidated. The purpose of this study
      was to describe the correlation between self-reported and behavioral pain scores
      in critically ill patients. METHODS: Pain was assessed using behavioral and self
      reported pain assessment tools. Behavioral pain tools included Critical Care Pain
      Observation Tool (CPOT) and Behavioral Pain Scale (BPS). Self-reported pain tools
      included Numeric Rating Scale (NRS) and Wong-Baker Faces Pain Scales. Delirium
      was assessed using the confusion assessment method for the intensive care unit.
      Patient preference regarding pain assessment method was queried. Correlation
      between scores was evaluated. RESULTS: A total of 115 patients were included: 67
      patients were nondelirious and 48 patients were delirious. The overall
      correlation between self-reported (NRS) and behavioral (CPOT) pain scales was
      poor (0.30, P = .018). In patients without delirium, a strong correlation was
      found between the 2 BPSs (0.94, P < .0001) and 2 self-reported pain scales (0.77,
      P < .0001). Self-reported pain scale (NRS) and BPS (CPOT) were poorly correlated
      with each other (0.28, P = .021). In patients with delirium, there was a strong
      correlation between BPSs (0.86, P < .0001) and a moderate correlation between
      self-reported pain scales (0.69, P < .0001). There was no apparent correlation
      between self-reported (NRS) and BPSs (CPOT) in patients with delirium (0.23, P =
      .12). Most participants preferred self-reported pain assessment. CONCLUSION: Self
      reported pain scale and BPS cannot be used interchangeably. Current validated
      BPSs may not accurately reflect self-reported pain in critically ill patients.

PMID- 29448872
TI  - Emotional Well-Being and Public Health: Proposal for a Model National Initiative.
AB  - In 2011, the National Prevention, Health Promotion, and Public Health Council
      named mental and emotional well-being as 1 of 7 priority areas for the National
      Prevention Strategy. In this article, we discuss emotional well-being as a
      scientific concept and its relevance to public health. We review evidence that
      supports the association between emotional well-being and health. We propose a
      national emotional well-being initiative and describe its 6 components:
      systematic measurement of emotional well-being, identification of the drivers of
      emotional well-being, formation of partnerships with diverse stakeholders,
      implementation and dissemination of evidence-based interventions to promote
      emotional well-being and its drivers, development of public health messaging, and
      identification of and strategies to address disparities in emotional well-being
      and its drivers. Finally, we discuss ways in which a national emotional well
      being initiative would complement current public health efforts and the potential
      challenges to such an initiative.

PMID- 29448874
TI  - Autobiographical memory functions and posttraumatic stress symptoms across
      adulthood.
AB  - Previous research has documented robust individual differences in the functions
      served by autobiographical memories, and shown that different autobiographical
      memory functions are related to both positive and negative indicators of
      psychological well-being, and that their frequency varies with age. In this
      study, we examined the unique relationship between autobiographical memory
      functions and posttraumatic stress symptoms (PTSS) and whether such relationships
      varied with age across adulthood. A representative sample of 1040 adult Danes (20
      70 years old) reported the frequency with which they recall autobiographical
      memories for different purposes as well as their level of posttraumatic stress
      disorder (PTSD) symptoms. Higher reflective and ruminative functions, as well as
      lower social function, predicted higher levels of PTSS. There were no moderating
      effects of age. The results suggest that although the frequency of various
      autobiographical functions varies throughout the adult years, their association
      with PTSS is similar across adulthood.

PMID- 29448875
TI  - Screening for cognitive impairment in an Australian aged care assessment team as
      part of comprehensive geriatric assessment.
AB  - Accurate detection of mild cognitive impairment (MCI) is important to stratify
      and address risk. Yet, few short cognitive screening instruments are validated
      for this. . In Australia, all clients referred to an Aged Care Assessment Team
      (ACAT) receive comprehensive geriatric assessment (CGA) including the
      Standardized Mini-Mental State Examination (SMMSE). We compared the accuracy of
      the quick mild cognitive impairment (Qmci) screen to the SMMSE in 283
      participants: 195 with dementia, 47 with MCI, and 41 with subjective cognitive
      decline (SCD) in an Australian community-based ACAT. Both had similar accuracy in
      identifying dementia, AUC of 0.86 for the Qmci versus 0.93 for the SMMSE (p =
      0.10), but the Qmci was more accurate than the SMMSE in differentiating MCI from
      SCD, AUC of 0.84 versus 0.71, respectively, p = 0.046. These suggest that the
      new, short (3-5 min) Qmci screenis appropriate for use in an ACAT or other units
      conducting CGA.

PMID- 29448876
TI  - Evaluation of injectable anaesthesia with five medetomidine-midazolam based
      combinations in Egyptian fruit bats ( Rousettus aegyptiacus).
AB  - Egyptian fruit bats are increasingly used as model animals in neuroscience
      research. Our aim was to characterize suitable injectable anaesthesia for this
      species, possibly replacing inhalant anaesthesia, thus minimizing occupational
      health hazards. Eight bats were randomly assigned by a crossover design for
      subcutaneously administered combinations of medetomidine-midazolam with: saline
      (MM-Sal), ketamine (MM-Ket), fentanyl (MM-Fen), morphine (MM-Mor), or butorphanol
      (MM-But). The anaesthetic depth and vital signs were monitored at baseline and
      every 10 min until bats recovered. If after 180 min the bats did not recover,
      atipamezole was administered. Mean induction times were 7-11.5 min with all
      combinations. Twitching during induction was common. All combinations produced
      anaesthesia, with significantly decreased heart rate (from 400 to 200 bpm) and
      respiratory rate (from 120-140 to 36-65 rpm). Arrhythmia and irregular breathing
      patterns occurred. MM-Fen, MM-Mor, and MM-But depressed respiration significantly
      more than MM-Sal. Time to first movement with MM-Ket and MM-But lasted
      significantly longer than with MM-Sal. Recovery time was significantly shorter in
      the MM-Sal (88 min) in comparison to all other treatments, and it was
      significantly longer in the MM-But (159 min), with atipamezole administered to
      four of the eight bats. In conclusion, all five anaesthetic protocols are
      suitable for Egyptian fruit bats; MM-Ket produces long anaesthesia and minimal
      respiratory depression, but cannot be antagonized completely. MM-Fen, MM-Mor, and
      MM-But depress respiration, but are known to produce good analgesia, and can be
      fully antagonized. Administration of atipamezole following the use of MM-But in
      Egyptian fruit bats is recommended.

PMID- 29448877
TI  - A new methodology for the measurement of the root canal curvature and its 3D
      modification after instrumentation.
AB  - OBJECTIVE: In this study, the three-dimensional (3D) modification of root canal
      curvature was measured, after the application of Reciproc instrumentation
      technique, by using cone beam computed tomography (CBCT) imaging and a special
      algorithm developed for the 3D measurement of the curvature of the root canal.
      MATERIALS AND METHODS: Thirty extracted upper molars were selected. Digital
      radiographs for each tooth were taken. Root curvature was measured by using
      Schneider method and they were divided into three groups, each one consisting of
      10 roots, according to their curvature: Group 1 (0 degrees -20 degrees ), Group 2
      (21 degrees -40 degrees ), Group 3 (41 degrees -60 degrees ). CBCT imaging was
      applied to each tooth before and after its instrumentation, and the data were
      examined by using a specially developed CBCT image analysis algorithm. RESULTS:
      The instrumentation with Reciproc led to a decrease of the curvature by 30.23%
      (on average) in all groups. CONCLUSIONS: The proposed methodology proved to be
      able to measure the curvature of the root canal and its 3D modification after the
      instrumentation.

PMID- 29448878
TI  - A method for preventive intervention regarding temporomandibular pain and
      dysfunction.
AB  - OBJECTIVE: Adolescent girls frequently suffer from temporomandibular disorder
      (TMD) symptoms and associated headache. A program aimed at informing about risk
      behavior for TMD symptoms, how to influence harmful habits and about general
      relaxation was tested. MATERIAL AND METHODS: Eighty girls at two high schools, 16
      years of age, with or without symptoms, were invited to the health information on
      two occasions and 60 girls participated. Firstly, a questionnaire regarding
      symptoms and oral parafunctional habits was administrated. Structured information
      was given about the normal anatomy and function of muscles and joints, about the
      occlusion, oral habits and symptoms of orofacial pain/dysfunction and headache.
      General relaxation was instructed and trained. At a three-month follow-up, the
      same questionnaire regarding symptoms as at baseline was completed. RESULT: The
      information provided was perceived as useful and instructive. At the follow-up,
      77% reported that they used what they had learned. Headache once a week or more
      decreased from 49% at baseline to 35% and headache 'never/rarely' changed from
      11% to 25% (p = .002). Reported joint sounds had decreased by the follow-up (p =
      .053), as had the use of chewing gum (p = .002). A majority of the girls
      suggested that the information should be scheduled during school hours.
      CONCLUSION: Health information about the jaw system can influence risk factors
      for TMD symptoms and the frequency of symptoms among adolescent girls.

PMID- 29448879
TI  - Extending access to care across the rural US south: Preliminary results from the
      Alabama eHealth programme.
AB  - Purpose Using a mixed-methods formative evaluation, the purpose of this study was
      to provide a broad overview of the Alabama eHealth programme set-up and initial
      patient outcomes. The Alabama eHealth programme uses telemedicine to provide
      medical care to people living with HIV in rural Alabama. It was led by a
      community-based organisation, Medical Advocacy and Outreach (MAO), and supported
      by AIDS United and the Corporation for National Community Service's Social
      Innovation Fund with matching support from non-federal donors. Methods We
      conducted and transcribed in-depth interviews with Alabama eHealth staff and then
      performed directed content analysis. We also tracked patients' ( n = 240)
      appointment attendance, CD4 counts, and viral loads. Findings Staff described the
      steps taken to establish the programme, associated challenges (e.g., costly,
      inadequate broadband in rural areas), and technology enabling this programme
      (electronic medical records, telemedicine equipment). Of all enrolled patients,
      76% were retained in care, 88% had antiretroviral therapy and 75% had a
      suppressed viral load. Among patients without missing data, 96% were retained in
      care, 97% used antiretroviral therapy and 93% had suppressed viral loads. There
      were no statistically significant demographic differences between those with and
      without missing data. Conclusions Patients enrolled in a telemedicine programme
      evaluation successfully moved through the HIV continuum of care.

PMID- 29448880
TI  - Migration and clinical outcome of mobile-bearing versus fixed-bearing single
      radius total knee arthroplasty.
AB  - Background and purpose - Mobile-bearing total knee prostheses (TKPs) were
      developed in the 1970s in an attempt to increase function and improve implant
      longevity. However, modern fixed-bearing designs like the single-radius TKP may
      provide similar advantages. We compared tibial component migration measured with
      radiostereometric analysis (RSA) and clinical outcome of otherwise similarly
      designed cemented fixed-bearing and mobile-bearing single-radius TKPs. Patients
      and methods - RSA measurements and clinical scores were assessed in 46 randomized
      patients at baseline, 6 months, 1 year, and annually thereafter up to 6 years
      postoperatively. A linear mixed-effects model was used to analyze the repeated
      measurements. Results - Both groups showed comparable migration (p = 0.3), with a
      mean migration at 6-year follow-up of 0.90 mm (95% CI 0.49-1.41) for the fixed
      bearing group compared with 1.22 mm (95% CI 0.75-1.80) for the mobile-bearing
      group. Clinical outcomes were similar between groups. 1 fixed-bearing knee was
      revised for aseptic loosening after 6 years and 2 knees (1 in each group) were
      revised for late infection. 2 knees (1 in each group) were suspected for
      loosening due to excessive migration. Another mobile-bearing knee was revised
      after an insert dislocation due to failure of the locking mechanism 6 weeks
      postoperatively, after which study inclusion was preliminary terminated.
      Interpretation - Fixed-bearing and mobile-bearing single-radius TKPs showed
      similar migration. The latter may, however, expose patients to more complex
      surgical techniques and risks such as insert dislocations inherent to this
      rotating-platform design.

PMID- 29448881
TI  - Outcomes of multitarget therapy using mycophenolate mofetil and tacrolimus for
      refractory or relapsing lupus nephritis.
AB  - Objectives Outcomes of systemic lupus erythematosus (SLE) have significantly
      improved over the years. However, when there is major organ involvement, the
      outcomes can still be unfavorable. Outcomes of multitarget therapy using
      mycophenolate mofetil (MMF) and tacrolimus in patients with SLE who were
      refractory to standard therapy were assessed. Methods We retrospectively reviewed
      the Hanyang BAE lupus cohort to identify patients with biopsy-confirmed lupus
      nephritis (classes III, IV, or V) who failed to either achieve complete response
      with standard induction therapy or those who had a lupus flare after achieving a
      complete response with conventional induction therapy and subsequently were
      switched to multitarget combination therapy with MMF and tacrolimus. Outcomes,
      including renal response, proteinuria, glomerular filtration rate, serum albumin,
      anti-dsDNA antibody level, Systemic Lupus Erythematosus Disease Activity Index
      (SLEDAI), and complements, were assessed at six and 12 months. Results Twenty
      nine patients, including 12 who failed to achieve a complete response at 12
      months after initial conventional induction therapy and 17 with lupus flare after
      achieving a complete response at 12 months and treated with multitarget therapy,
      were included in the analysis. At six months, 53.9% of the patients showed a
      response, with 15.4% of patients showing a complete response and 38.5% of
      patients showing a partial response. At 12 months, 55.5% of patients exhibited a
      response (with complete and partial response in 25.9% and 29.6%, respectively).
      The dosage of steroids was significantly decreased at six months compared with
      baseline and was maintained at 12 months. Proteinuria, anti-double-stranded DNA
      antibody positivity, as well as C3 and C4 levels improved after treatment and
      persisted until 12 months, but were not significant. SLEDAI also improved.
      Outcomes were significantly better in patients who had a complete response but
      later had a flare, resulting in the use of multitarget therapy and achieving a
      subsequent complete response. Conclusions Multitarget therapy with MMF and
      tacrolimus can be a reasonable option in refractory lupus nephritis patients who
      failed to show adequate response to conventional induction therapy or who had
      flares during maintenance therapy. This treatment can help patients achieve a
      renal response and reduce the use of steroids.

PMID- 29448882
TI  - Multitarget therapy of mycophenolate mofetil and cyclosporine A for induction
      treatment of refractory lupus nephritis.
AB  - Standard induction therapy for lupus nephritis (LN) with mycophenolate mofetil
      (MMF) or cyclophosphamide (CYC) is often ineffective. Evidence on rescue
      induction regimens is scarce. We analyzed efficacy and tolerability of
      multitarget immunosuppression with MMF and cyclosporine A (CsA) as induction
      treatment for LN (class III/IV/V) refractory to CYC and/or MMF. We included all
      six refractory LN patients (class IV = 3, class V = 2, class III = 1) from our
      400-patient tertiary Lupus Clinic observed between 2012 and 2015. Four patients
      had previously received pulse CYC. All six received MMF as first or second
      induction therapy and CsA was added once failure to reach remission was
      established. Daily dose of MMF was 2-3 g and CsA was dosed up to 2.6-3.7
      mg/kg/day. Mean proteinuria was reduced from 2407 mg/24 hours at the start of the
      MMF+CsA regimen to 544 mg/day after six months. The mean prednisolone dose was
      reduced from 17.5 to 6 mg/day after six months of MMF+CsA. Four patients achieved
      a complete renal response, one patient had a partial renal response and one
      failed to respond. None of the patients presented with adverse events. These data
      suggest that adding CsA to MMF can induce complete remission of refractory LN and
      is well tolerated.

PMID- 29448883
TI  - Natural Frequencies Do Foster Public Understanding of Medical Tests: Comment on
      Pighin, Gonzalez, Savadori, and Girotto (2016).
AB  - Patients and doctors often need to make decisions based on the results of medical
      tests. When these results are presented in the form of conditional probabilities,
      even doctors find it difficult to interpret them correctly. There is over 20 y of
      research supporting the finding that people are better able to calculate the
      correct positive predictive value of a test when given information in natural
      frequencies, as opposed to conditional probabilities. Natural frequencies are one
      of a few psychological tools that have made it into evidence-based medicine.
      Recently, Pighin and others (Med Decis Making 2016;36:686-91) argued that natural
      frequencies could hinder informed decision making, a critique based on a single
      task and a crude scoring criterion we refer to as the 50%-Split. Our commentary
      addresses these criticisms based on three analyses. First, we show how the 50%
      Split scoring used by Pighin and others misclassifies known errors, such as
      solely attending to the hit rate (true-positive rate) of the test, as strategies
      that support understanding. Second, we reanalyze data from 21 additional problems
      completed by various participant groups to show that their scoring criterion does
      not support their results in 19 out of 21 cases. Third, we apply the mean
      deviation scoring method and show that, when given information in natural
      frequency formats, participants provide estimates that are closer to the correct
      Bayesian solution than for conditional probability formats. In each analysis,
      natural frequencies lead to more correct judgements and therefore promote
      informed decision making relative to conditional probabilities. We welcome
      further discussions of performance metrics that can provide insight into how the
      public and therefore patients understand the implications of medical test
      results.

PMID- 29448884
TI  - Ameliorating the in vivo antimalarial efficacy of artemether using nanostructured
      lipid carriers.
AB  - Cerebral malaria (CM) is a fatal neurological complication of Plasmodium
      falciparum infection that affects children (below five years old) in sub-Saharan
      Africa and adults in South-East Asia each year having the fatality rate of 10
      25%. The survivors of CM also have high risk of long term neurological or
      cognitive deficits. The objective of the present investigation was to develop
      optimised nanostructured lipid carriers (NLCs) of artemether (ARM) for enhanced
      anti-malarial efficacy of ARM. NLCs of ARM were prepared by a combination of high
      speed homogenisation (HSH) and probe sonication techniques. Preliminary
      solubility studies for ARM showed highest solubility in trimyristin (solid
      lipid), capmul MCM NF (liquid lipid) and polysorbate 80 (surfactant). Trimyristin
      and capmul showed superior miscibility at a ratio of 70:30.The optimised NLC
      formulation has the particle size (PS) of: 48.59 +/- 3.67 nm, zeta potential (ZP)
      of: -32 +/- 1.63 mV and entrapment efficiency (EE) of: 91 +/- 3.62%. In vitro
      cell line (human embryonic kidney fibroblast cell line (HEK 293 T)) cytotoxicity
      studies showed that prepared formulation was non-toxic. The results of in vivo
      studies in CM induced mice prevented the recrudescence of parasite after
      administration of NLCs of ARM. Additionally, NLCs of ARM showed better parasite
      clearance, higher survival (60%) in comparison to ARM solution (40%). Also it was
      observed that lesser entrapment of Evans blue stain (prepared in PBS as solution)
      in the NLCs of ARM treated brains of C57BL/6 mice than ARM solution treated mice.
      Hence NLCs of ARM may be a better alternative for improving therapeutic efficacy
      than ARM solution.

PMID- 29448885
TI  - "Recognize Our Humanity": Immigrant Youth Voices on Health Care in Arizona's
      Restrictive Political Environment.
AB  - The "DACAmented Voices in Healthcare" project examined the intersection of
      restrictive immigration policies and health care via photovoice, a participatory
      action research approach, with immigrant youth living in Arizona, who were
      recipients of the Deferred Action for Childhood Arrivals (DACA) program. These
      "DACAmented" youth took part in nine photovoice sessions exploring their health
      care experiences and accessibility to care using documentary photography and
      narratives. They poignantly illustrated their experiences through images
      identifying their main health concerns and strengths, facilitating the
      development of health policy recommendations. This article illustrates the
      thematic findings and discusses policy recommendations and lessons learned from
      presentations to policy makers and health care providers. Findings suggest that
      immigrant youth are knowledgeable of their family's health care needs and hold a
      unique and important position within mixed-status households. Health care
      providers can benefit from the proposed recommendations by building bridges to
      care to address health equity in immigrant communities.

PMID- 29448886
TI  - Augmenting treatment efficiency in exposure therapy for PTSD: a randomized double
      blind placebo-controlled trial of yohimbine HCl.
AB  - The alpha-2 adrenergic receptor antagonist, yohimbine, can facilitate fear
      extinction in animals and humans. One potential mechanism is increased
      noradrenergic activity and associated arousal in the presence of conditioned
      stimuli. Accordingly, yohimbine might augment prolonged exposure (PE) therapy for
      posttraumatic stress disorder (PTSD), where heightened exposure-oriented arousal
      is a theorized driver and empirical predictor of treatment success. A double
      blind placebo-controlled randomized trial (NCT 01031979) piloted yohimbine
      augmentation in 26 males with combat-related PTSD. Participants were given one
      time dose of yohimbine or placebo prior to the first imaginal exposure.
      Subsequently, both arms completed standard PE. The primary outcome was trauma
      cued heart-rate reactivity a week after the drug/exposure visit, a highly
      specified, objective measure sensitive to incremental change. Secondary outcomes
      included arousal during the drug/exposure visit and slope of distress, PTSD, and
      depression over the course of PE. Consistent with hypothesis, yohimbine led to
      higher objective and subjective arousal during the drug/exposure visit and to
      lower trauma-cued heart-rate reactivity one-week later. One dose of yohimbine
      also led to greater between-session habituation and more rapid improvement on
      depression, but not PTSD, over the course of care. Results of this controlled
      pilot indicate support for continued investigation of yohimbine-augmented
      exposure therapy for PTSD.

PMID- 29448887
TI  - Fabrication of iron oxide nanocolloids using metallosurfactant-based
      microemulsions: antioxidant activity, cellular, and genotoxicity toward Vitis
      vinifera.
AB  - The present work aims at the fabrication of iron oxide nanocolloids using
      biocompatible microemulsion and their cytotoxic, genotoxic effect on Vitis
      vinifera plant has been evaluated. The three iron-based metallosurfactant
      complexes were synthesized. Nanosuspensions (Ns) were prepared using
      microemulsion technique and for the purpose, the microemulsion was prepared using
      oleic acid, butanol, tween 80 and as synthesized iron metallosurfactant. In this
      technique, no additional capping agent and/or reducing agent was added. Tween 80
      which is a biocompatible surfactant acted as a reducing agent as well as
      stabilizing for the iron oxide Ns. Characterization of Ns's was done using TEM,
      FESEM, EDX, XRD, AFM, and zeta potential. Mixed type of iron oxide nanoparticles
      i.e. magnetite (Fe3O4), and maghemite (Fe2O3) with a size range of 1-16 nm was
      found to be present in the nanosuspensions prepared from all the three
      precursors. The antioxidant activity of the Fe Ns was also confirmed using DPPH
      assay, with order of activity FeDDA > FeCTAC > FeHEXA. The cellular toxicity of
      Ns was evaluated by observing the morphological changes on V. vinifera plant
      (petiole) using a light microscope. Further, the interactions of iron oxide Ns
      with V. vinifera's DNA (plant-DNA) was assessed using circular dichroism (CD) and
      gel electrophoresis. For the case of FeCTAC Ns, a decrease in the intensity of
      bands was observed indicating fragmentation or adduct formation resulting in DNA
      damage. In the case of FeDDA, a modest decrease in the intensity of bands was
      observed. However, for FeHEXA Ns, complete neutralization of bands was confirmed
      implying maximum damage to the plant DNA. CD, gel electrophoresis and antioxidant
      activity confirmed that FeHEXA Ns were most toxic and FeDDA Ns were safest among
      the three as-fabricated nanosuspensions.

PMID- 29448888
TI  - Cross-Linked Cholecyst-Derived Extracellular Matrix for Abdominal Wall Repair.
AB  - Abdominal wall repair frequently utilizes either nondegradable or biodegradable
      meshes, which are found to stimulate undesirable biological tissue responses or
      which possess suboptimal degradation rate. In this study, a biologic mesh
      prototype made from carbodiimide cross-linked cholecyst-derived extracellular
      matrix (EDCxCEM) was compared with small intestinal submucosa (Surgisis(r)),
      cross-linked bovine pericardium (Peri-Guard(r)), and polypropylene (Prolene(r))
      meshes in an in vivo rabbit model. The macroscopic appearance and stereological
      parameters of the meshes were evaluated. Tailoring the degradation of the EDCxCEM
      mesh prevents untimely degradation, while allowing cellular infiltration and mesh
      remodeling to take place in a slower but predictable manner. The results suggest
      that the cross-linked biodegradable cholecyst-derived biologic mesh results in no
      seroma formation, low adhesion, and moderate stretching of the mesh. In contrast
      to Surgisis, Peri-Guard, and Prolene meshes, the EDCxCEM mesh showed a
      statistically significant increase in the volume fraction (Vv) of collagen (from
      34% to 52.1%) in the central fibrous tissue region at both day 28 and 56. The
      statistically high length density (Lv), of blood vessels for the EDCxCEM mesh at
      28 days was reflected also by the higher cellular activity (high Vv of fibroblast
      and moderate Vv of nuclei) indicating remodeling of this region in the vicinity
      of a slowly degrading EDCxCEM mesh. The lack of mesh area stretching/shrinkage in
      the EDCxCEM mesh showed that the remodeled tissue was adequate to prevent hernia
      formation. The stereo-histological assays suggest that the EDCxCEM delayed
      degradation profile supports host wound healing processes including collagen
      formation, cellular infiltration, and angiogenesis. The use of cross-linked CEM
      for abdominal wall repair is promising.

PMID- 29448889
TI  - Potential of the Moringa oleifera saline extract for the treatment of dairy
      wastewater: application of the response surface methodology.
AB  - In this work, the coagulation/flocculation/sedimentation treatment of dairy
      wastewater samples was investigated through serial factorial designs utilizing
      the saline extract obtained from Moringa oleifera (Moringa) as a coagulant. The
      sedimentation time (ST), pH, Moringa coagulant (MC) dose and concentration of
      CaCl2 have been evaluated through the response surface methodology in order to
      obtain the ideal turbidity removal (TR) conditions. The empirical quadratic
      model, in conjunction with the desirability function, demonstrated that it is
      possible to obtain TRs of 98.35% using a coagulant dose, concentration of CaCl2
      and pH of 280 mg L-1, 0.8 mol L-1 and 9, respectively. The saline extract from
      Moringa presented its best efficiency at an alkaline pH, which influenced the
      reduction of the ST to a value of 25 min. It was verified that the increase in
      the solubility of the proteins in the Moringa stimulated the reduction of the
      coagulant content in the reaction medium, and it is related to the use of calcium
      chloride as an extracting agent of these proteins. The MC proved to be an
      excellent alternative for the dairy wastewater treatment, compared to the
      traditional coagulants.

PMID- 29448890
TI  - Evaluation of hybrid neutralization/biosorption process for zinc ions removal
      from automotive battery effluent by dolomite and fish scales.
AB  - This work focused in the evaluation of Oreochromis niloticus fish scales (FS) as
      biosorbent material in the removal of Zn from a synthetic effluent based on
      automotive battery industry effluent and, further, a hybrid
      neutralization/biosorption process, aiming at a high-quality treated effluent, by
      a cooperative use of dolomite and FS. For this, a physicochemical and
      morphological characterization (i.e. SEM-EDX, FTIR, XRD, and TXRF) was performed,
      which helped to clarify a great heterogeneity of active sites (phosphate,
      carbonate, amide, and hydroxyl) on the biosorbent; also the inorganic
      constituents (apatites) leaching from the FS was identified. Biosorption results
      pointed out to a pH-dependent process due to changes in the functional group's
      anionic character (i.e. electrostatic interactions), where an initial pH = 3
      favored the Zn uptake. Kinetic and equilibrium studies confirmed the
      heterogeneous surface and cooperative sorption, wherein experimental data were
      described by Generalized Elovich kinetic model and the favorable isotherm profile
      by Langmuir-Freundlich isotherm ([Formula: see text] = 15.38 mg g-1 and [Formula:
      see text]). Speciation diagram of Zn species along with the leached species
      demonstrated that, for the studied pH range, the biosorption was the most likely
      phenomena rather than precipitation. Finally, the hybrid
      neutralization/biosorption process showed great potential since both the Zn
      concentration levels and the pH reached the legislation standards (CZn = 4 mg L
      1; pH = 5). Hence, based on the characterization and biosorption results, a
      comprehensive evaluation of the involved mechanisms in such complex system helped
      to verify the prospective of FS biosorbent for the Zn treatment from solution, in
      both individual and hybrid processes.

PMID- 29448891
TI  - Impact of landfill density on transport and hydraulic characteristics of
      recirculated leachate.
AB  - To achieve a uniform water distribution and to promote the stabilization of
      bioreactor landfills, the effects of different density on the transport and
      hydraulic characteristics of recirculated leachate were studied in a Li+ tracer
      experiment. The landfill density was related negatively to the maximum production
      rate of leachate, the percentage of Li+ tracer solution and the cumulative amount
      of Li+ that washed out in the first recirculation round. The cumulative amount of
      Li+ that was washed out accounted for 92.61%, 82.07% and 75.25% of the injection
      volume in three waste columns (1#, 2# and 3#) with landfill densities of 497.5,
      726.4 and 970.1 kg m-3 at the thirtieth recirculation, respectively. The results
      revealed that a greater landfill density yielded a smaller amount of Li+ that was
      washed out per recirculation cycle and the cumulative amount of Li+ washed out,
      and a longer contact time between the waste and leachate. Moreover, waste columns
      1#, 2# and 3# are reactors with a high dispersion and obvious retention zones,
      and their Morrill Dispersion Index (MDI) values were 25.00, 34.51 and 24.55,
      respectively. A short-flow phenomenon is obvious in the reactor with a low
      landfill density. Furthermore, the plug-flow effect is relatively better in the
      reactor with a high landfill density. To achieve a uniform distribution of
      recirculated leachate in the landfill, the MDI of the reactor should be reduced
      combined with other measures, such as pre-crushing and different recirculation
      schemes.

PMID- 29448892
TI  - Examining the role of racism in the risky alcohol use behaviors of black female
      college students.
AB  - OBJECTIVE: This study explores the impact racism has on the drinking behaviors of
      Black college women. Little is known about Black college women's experience of
      racism and the impact racism has on their psychological wellbeing and drinking
      behaviors. The current study fills a gap in our understanding of the role racism
      plays in the risky drinking behavior of Black college women. PARTICIPANTS: 469
      Black college women ages 18-29 were sampled from 8 colleges and universities
      across the US, in 3 waves from December 2014-August 2017. RESULTS: Findings
      suggest that general life stress and perceived racism are significantly
      associated with alcohol use among Black college women. However, only increased
      experiences of racism increase Black college women's engagement in risky
      drinking. CONCLUSIONS: The findings of this study serve as an entry point for a
      more nuanced assessment of stressors among Black college women that may inform
      drinking behaviors in this population.

PMID- 29448893
TI  - Arsenic species in rice and rice-based products consumed by toddlers in
      Switzerland.
AB  - Inorganic arsenic (iAs) is a contaminant present in food, especially in rice and
      rice-based products. Toxicity of arsenic compounds (As) depends on species and
      oxidative state. iAs species, such as arsenite (As(III)) and arsenate (As(V)),
      are more bioactive and toxic than organic arsenic species, like methylarsonic
      acid (MMA(V)) and dimethylarsinic acid (DMA(V)) or arsenosugars and
      arsenobetaine. An ion chromatography-inductively coupled-plasma-mass spectroscopy
      method was developed to separate the four following arsenic anions: As(III),
      As(V), MMA(V) and DMA(V). Sample preparation was done in mild acidic conditions
      to ensure species preservation. The predominant arsenic species found in rice and
      rice-based products, except for rice drinks, was As(III), with 60-80% of the
      total As content, followed by DMA(V) and As(V). MMA(V) was measured only at low
      levels (<3%). Analyses of rice products (N = 105) intended for toddlers,
      including special products destined for infants and toddlers, such as dry form
      baby foods (N = 12) or ready-to-use form (N = 9), were done. It was found in this
      study that there is little or no margin of exposure. Risk assessment, using the
      occurrence data and indicated intake scenarios compared to reference BMDLs as
      established by EFSA, demonstrated toddlers with a high consumption of rice based
      cereals and rice drinks are at risk of high iAs exposure, for which a potential
      health risk cannot be excluded.

PMID- 29448894
TI  - Noninvasive Optical Assessment of Implanted Engineered Tissues Correlates with
      Cytokine Secretion.
AB  - Fluorescence lifetime sensing has been shown to noninvasively characterize the
      preimplantation health and viability of engineered tissue constructs. However,
      current practices to monitor postimplantation construct integration are either
      qualitative (visual assessment) or destructive (tissue histology). We employed
      label-free fluorescence lifetime spectroscopy for quantitative, noninvasive
      optical assessment of engineered tissue constructs that were implanted into a
      murine model. The portable system was designed to be suitable for intravital
      measurements and included a handheld probe to precisely and rapidly acquire data
      at multiple sites per construct. Our model tissue constructs were manufactured
      from primary human cells to simulate patient variability based on a standard
      protocol, and half of the manufactured constructs were stressed to create a range
      of health states. Secreted amounts of three cytokines that relate to cellular
      viability were measured in vitro to assess preimplantation construct health:
      interleukin-8 (IL-8), human beta-defensin 1 (hBD-1), and vascular endothelial
      growth factor (VEGF). Preimplantation cytokine secretion ranged from 1.5 to 33.5
      pg/mL for IL-8, from 3.4 to 195.0 pg/mL for hBD-1, and from 0.1 to 154.3 pg/mL
      for VEGF. In vivo optical sensing assessed constructs at 1 and 3 weeks
      postimplantation. We found that at 1 week postimplantation, in vivo optical
      parameters correlated with in vitro preimplantation secretion levels of all three
      cytokines (p < 0.05). This correlation was not observed in optical measurements
      at 3 weeks postimplantation when histology showed that the constructs had re
      epithelialized, independent of preimplantation health state, supporting the lack
      of a correlation. These results suggest that clinical optical diagnostic tools
      based on label-free fluorescence lifetime sensing of endogenous tissue
      fluorophores could noninvasively monitor postimplantation integration of
      engineered tissues.

PMID- 29448895
TI  - The Outcome of Anticoagulation on Endovenous Laser Therapy for Superficial Venous
      Incompetence.
AB  - OBJECTIVES: The purpose of this study was to evaluate whether anticoagulation
      (warfarin or direct oral inhibitors) affected the success of endovenous
      treatment. METHODS: Patients taking anticoagulation (warfarin or direct oral
      inhibitors) undergoing endovenous treatment in the form of endovenous laser
      ablation (EVLA) were matched against controls for sex, age, leg, and vein. Data
      were collected prospectively between January 2012 and March 2017. The primary
      endpoint was failure of treatment at 6-week postoperative duplex scan. The rates
      of major bleeding, hematoma, endothermal heat-induced thrombosis, venous
      thromboembolism, or pulmonary embolism were also compared between groups.
      RESULTS: Two hundred eighty-four limbs underwent EVLA during the study period. Of
      this, 23/284 (8.1%) procedures were done in patients on anticoagulation. 21/23
      (91.3%) limbs had venous occlusion at follow-up compared with 23/23 (100%) of
      controls ( P = .49). The patient who failed treatment in the anticoagulation
      group had undergone small saphenous vein (SSV) ablation. There was no difference
      in the complication rates between groups. DISCUSSION: This study demonstrates
      that anticoagulation does not affect success rates of EVLA though there was
      higher recanalization rate in patients undergoing SSV ablation. Anticoagulation
      can be continued safely in patients undergoing this procedure.

PMID- 29448896
TI  - Circulating Neutrophil Extracellular Traps Are Elevated in Patients With Deep
      Infiltrating Endometriosis.
AB  - Neutrophil extracellular traps (NETs) have been described to be related to the
      pathogenesis of inflammatory and autoimmune conditions. Endometriosis is
      currently considered a chronic inflammatory condition. Therefore, we performed a
      preliminary case-control study to compare the circulating plasma NET levels in
      patients with surgically confirmed endometriosis (E group, n = 82) and those of
      patients without surgical findings of endometriosis (C group, n = 35). Venous
      blood samples were obtained at the time of surgery. Circulating plasma NET levels
      were assessed as histone-DNA complexes (ie, nucleosomes) by a quantitative
      sandwich enzyme-linked immunosorbent assay. The results were expressed in
      arbitrary units. Circulating plasma NET levels were significantly higher in the E
      group compared with the C group (median [25th; 75th percentiles]): E group: 0.734
      [0.484; 1.363]; C group: 0.541 [0.411; 0.653]; P = .005). The subanalysis of E
      group patients with deep infiltrating endometriosis (DIE group) or without DIE
      (non-DIE group) showed that plasma NET levels were higher in the DIE group ( P =
      .02). No differences were observed in NET levels among patients with and without
      severe pelvic pain or in patients with and without infertility, regardless of the
      presence of endometriotic lesions. Therefore, our study shows significantly
      higher NET levels in patients with endometriosis, which seem to be attributed to
      increased levels in the subgroup of patients with DIE, suggesting that the
      presence of elevated circulating plasma NET levels may reflect an inflammatory
      status in this gynecological condition. Further research is warranted to confirm
      our findings and to assess the exact role of NETs in the pathophysiological
      mechanisms of endometriosis.

PMID- 29448897
TI  - Immunomodulation by food: impact on gut immunity and immune cell function.
AB  - Recent studies have revealed that various food components affect the immune
      response. These components act on various immune cells, and their effects are
      mediated through the intestinal immune system and, in some cases, the intestinal
      microbiota. In this review, we describe the immunomodulating effects of various
      food components, including probiotics, prebiotics, polysaccharides, vitamins,
      minerals, fatty acids, peptides, amino acids and polyphenols. Some of these
      components enhance immune responses, leading to host defense against infection,
      whereas others inhibit immune responses, thus suppressing allergy and
      inflammation.

PMID- 29448898
TI  - A membrane aerated biofilm reactor for sulfide control from anaerobically treated
      wastewater.
AB  - A upflow anaerobic sludge blanket reactor was operated combined to a membrane
      aerated biofilm reactor for sulfate removal and for elemental sulfur reclamation.
      A commercial silicon tube was used as an oxygen delivery diffuser. The process
      achieved high rates of sulfide removal from the liquid phase (90%). The hydrogen
      sulfide removal was influenced by the pH value and at pH value of 7.5, 98% of the
      H2S was removed. The elemental sulfur was observed inside the membrane, with
      content in the biomass of 21%. Through the massive sequencing of the samples, the
      microbial community diversity and the stratification of biomass inside the
      silicon tube was demonstrated, confirming the presence of sulfide-oxidizing
      bacteria on the membrane wall. The most important genera found related to the
      sulfur cycle were Sulfuricurvum, Geovibrio, Flexispira and Sulforospirillum.

PMID- 29448899
TI  - Dietary exposure of the Belgian population to emulsifiers E481 (sodium stearoyl-2
      lactylate) and E482 (calcium stearoyl-2-lactylate).
AB  - A dietary exposure assessment of food emulsifiers E481 (sodium stearoyl-2
      lactylate) and E482 (calcium stearoyl-2-lactylate) in the Belgian population was
      performed. Nationally representative food consumption data from the Belgian
      National Food Consumption Surveys 2004 (BNFCS2004) and 2014 (BNFCS2014) were used
      for calculations. A conservative approach (combining individual food consumption
      data with the maximum permitted level (MPL) of foods (tier 2), was compared with
      more refined estimates (combining individual food consumption data with actual
      concentrations measured in food products available on the Belgian market (tier
      3)). Estimated daily intakes were compared to the acceptable daily intake (ADI)
      of the stearoyl-2-lactylates. The results of tier 2 demonstrated that 92% of the
      children (3-9 years), 53% of the adolescents (10-17 years), 15% of the adults (18
      64 years) and 26% of the elderly (64-98 years) had a potential intake higher than
      the ADI. When replacing the MPL with maximum analysed concentration levels in
      foods, daily intake estimates decreased dramatically. The estimated daily intake
      of the food emulsifiers was below the ADI for all age groups, except for a small
      percentage of children (1.9%) for which the intake exceeded the ADI. The main
      contributors to the exposure of E481 and E482 were bread, rolls and fine bakery
      wares.

PMID- 29448900
TI  - Provision of surgical care in Ethiopia: Challenges and solutions.
AB  - : With the lowest measured rate of surgery in the world, Ethiopia is faced with a
      number of challenges in providing surgical care. The aim of this study was to
      elucidate challenges in providing safe surgical care in Ethiopia, and solutions
      providers have created to overcome them. Semi-structured interviews were
      conducted with 10 practicing surgeons in Ethiopia. Following de-identification
      and immersion into field notes, topical coding was completed with an existing
      coding manual. Codes were adapted and expanded as necessary, and the primary data
      analyst confirmed reproducibility with a secondary analyst. Qualitative analysis
      revealed topics in access to care, in-hospital care delivery, and health policy.
      Patient financial constraints were identified as a challenge to accessing care.
      Surgeons were overwhelmed by patient volume and frustrated by lack of material
      resources and equipment. Numerous surgeons commented on the inadequacy of
      training and felt that medical education is not a government priority. They
      reported an insufficient number of anaesthesiologists, nurses, and support staff.
      Perceived inadequate financial compensation and high workload led to low morale
      among surgeons. Our study describes specific challenges surgeons encounter in
      Ethiopia and demonstrates the need for prioritisation of surgical care in the
      Ethiopian health agenda. ABBREVIATIONS: LCoGS: The Lancet Commission on Global
      Surgery; LMIC: low- and middle-income country.

PMID- 29448901
TI  - The Future of the History of Chemistry.

PMID- 29448902
TI  - The Altmetric Attention Score: What Does It Mean and Why Should I Care?

PMID- 29448903
TI  - Effects of different types of soy sauce on the formation of heterocyclic amines
      in roasted chicken.
AB  - The objective of the study was to determine the effect of different types of soy
      sauce and marinating time on the formation of heterocyclic amines (HCAs) in
      roasted chicken. Chicken breast samples were marinated with sweet, salty, light
      and dark soy sauce at 0, 3, 6 and 12 h (control treatment was the chicken without
      marinade). The concentrations of free amino acids, sugars and creatinine were
      determined before roasting while HCA concentrations were determined after
      roasting. All types of soy sauce significantly increased (p <= 0.05) the
      concentration of HCAs in roasted chicken with increasing marinating time. The
      highest increment of total concentration of HCAs was found in samples marinated
      with light soy sauce (887%) followed by dark (375%), salty (193%) and sweet
      (169%) at 12 h. PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine) showed a
      substantial reduction in samples only momentarily marinated with sweet, salty and
      dark soy sauce (0 h). Free amino acids were found to be more strongly correlated
      with the formation of HCAs than reducing sugars or creatinine.

PMID- 29448904
TI  - Proliferative Lesions of the Endometrium of 50 Four-Toed Hedgehogs ( Atelerix
      albiventris).
AB  - Uteri from 50 four-toed hedgehogs ( Atelerix albiventris) with clinical signs of
      uterine disease were histopathologically examined. Sixteen animals (32%) were
      diagnosed with endometrial hyperplasia, 7 animals (14%) were diagnosed with
      endometrial polyp, and 27 animals (54%) were diagnosed with endometrial
      neoplasia. The mean ages of the animals with endometrial hyperplasia, polyp, and
      neoplasia were 28.7 months, 29.4 months, and 25.2 months, respectively. The
      neoplasms were classified into 7 endometrial mixed tumors, 12 endometrial stromal
      nodules, and 8 endometrial stromal sarcomas. However, the endometrial stromal
      nodules and endometrial stromal sarcomas often developed within or were
      contiguous with an endometrial polyp or mixed tumor. Interestingly, the stromal
      tumors and the stromal components of the endometrial polyp and mixed tumor
      displayed extraendometrial differentiation (eg, into adipocytes, granular cells,
      smooth muscle cells, and osteoid tissue). The endometrial stromal sarcomas
      exhibited severe cellular atypia and invaded subendometrial tissue.
      Immunohistochemical examinations demonstrated that the stromal cells of the
      hyperplastic lesions as well as the neoplastic lesions were positive for CD10,
      the progesterone receptor, and Wilms tumor 1. The four-toed hedgehog develops
      unique uterine neoplasms that are mainly composed of endometrial stromal cells
      and probably arise from endometrial polyps and/or mixed tumors.

PMID- 29448905
TI  - Restoration of sleep using a novel biomimetic protocol for adult OSA: Clinical
      case report.
AB  - Background A sleep study of a 56-year old male with excessive daytime sleepiness
      demonstrated an AHI of 16.4hr-1 with 13% of total sleep time in REM sleep and a
      mean oxygen desaturation (SpO2) of 86%. Clinical presentation On intra-oral
      examination, it was found that the patient had maxillary hypoplasia and bilateral
      torus mandibularis. A 3D cone-beam CT (CBCT) scan was taken, and 28 craniofacial
      parameters were measured. Surgical reduction of the mandibular tori followed by
      biomimetic oral appliance therapy (BOAT) was initiated. After 14 months, a post
      treatment CBCT scan revealed that 70% of parameters measured had improved.
      Therefore, another sleep study was performed with no device in the mouth. This
      follow-up home sleep test demonstrated that the AHI fell to 5.3hr-1hr; with 27%
      REM sleep, and a mean SpO2 of 93% without any device in the mouth. Conclusion
      These findings suggest that BOAT might be able to restore sleep in certain adult
      cases.

PMID- 29448906
TI  - Violence and Abuse in Rural Older Women's Lives: A Life Course Perspective.
AB  - Intimate partner violence in later life includes physical, psychological, sexual,
      and financial abuse. Although some researchers have investigated how women in
      long-term violent partnerships cope with abuse, little is known about the
      history, experiences, and needs of older women who leave abusive relationships.
      From a feminist, life course perspective, we interviewed 10 women who had left
      their abusive partners later in life. We used qualitative methods to analyze the
      data and found four major themes: (a) the women used the past to account for
      abuse in their relationships later in life, (b) recognizing abuse signaled to the
      women to fight back and exit the relationship, (c) financial abuse and
      exploitation affected women's mental and physical health, and (d) rebuilding was
      especially challenging as the women faced their future alone with financial,
      physical, or mental health problems. We conclude that abuse presents lasting and
      unique challenges for older women.

PMID- 29448907
TI  - Disclosure of Sexual Violence Among Girls and Young Women Aged 13 to 24 Years:
      Results From the Violence Against Children Surveys in Nigeria and Malawi.
AB  - Understanding factors that are associated with disclosure of sexual violence (SV)
      is important for the delivery of health services as well as developing strategies
      for prevention and response. The Violence Against Children Surveys were conducted
      in Malawi and Nigeria. We examined the prevalence of SV, help-seeking behaviors,
      and factors associated with disclosure among girls and young women aged 13 to 24.
      The self-reported prevalence of SV was similar in Nigeria (26%) and Malawi (27%).
      Among females who experienced SV, approximately one third (37%) in Nigeria and
      one half (55%) in Malawi ever disclosed their experience of SV. Females in
      Nigeria were significantly more likely to disclose to their parents (31.8%) than
      females in Malawi (9.5%). The most common reason for nondisclosure in Nigeria was
      not feeling a need or desire to tell anyone (34.9%) and in Malawi was
      embarrassment (29.3%). Very close relationships with one or both parents were
      significantly associated with disclosure among Nigerian females (odds ratio [OR]
      = 5.5, 95% confidence interval [CI] = [2.1, 14.6]) but were inversely associated
      with disclosure among Malawian females (OR = 0.05, 95% CI = [0.01, 0.33]).
      Reasons for nondisclosure of SV and factors associated with disclosure among
      females differ in the African nations studied. The stigma associated with shame
      of SV may prevent females from disclosing and thus receiving necessary support
      and health, social, and other services. This study demonstrates a need to reduce
      barriers for disclosure to improve the delivery of health, social, and other
      response services across African nations, as well as to develop culturally
      appropriate strategies for its response.

PMID- 29448908
TI  - The Role of Cultural Factors on Dating Aggression and Delinquency Among Latino
      Youth.
AB  - There is limited research comparatively evaluating delinquency and dating
      aggression among Latino youth. This analysis examines the rates and cultural
      correlates associated with delinquency and dating aggression among Latino youth
      using data from the Dating Violence Among Latino Adolescents study. The study
      surveyed 1,525 Latino adolescents between the ages of 12 and 18 years about past
      year dating aggression perpetration and delinquency. Dating aggression
      perpetration and delinquency rates and relative risk ratios are presented.
      Logistic regression analyses examined the role of cultural factors on the
      perpetration of dating aggression and delinquent behaviors. Results showed that
      cultural factors had differential influence on dating aggression versus
      delinquency. Specifically, victimization, acculturation, and familial support
      were associated with dating aggression whereas only victimization and familial
      support were associated with delinquency. The results provide guidance for
      intervention and prevention efforts with Latino youth, particularly on the need
      for cultural consideration and the supportive role family can play in addressing
      these behaviors.

PMID- 29448909
TI  - A Preliminary Investigation Into a Range of Implicit and Explicit Offense
      Supportive Cognitions in Perpetrators of Physical Intimate Partner Violence.
AB  - The current study assessed a wide range of offense supportive cognitions in
      relation to the perpetration of physical intimate partner violence (IPV). This
      research used both implicit and explicit measures in a U.K. sample of 19 male IPV
      perpetrators recruited from a community-based IPV intervention program and 20 men
      from the community with no history of IPV. The study also explored the ability of
      the implicit measures to differentiate between the two groups. The cognitions
      assessed included gender-role stereotype, attitudes condoning violence against a
      partner, attitudes condoning violence in general, hostile attitudes toward women,
      sense of entitlement in the relationship and over the intimate partner (control
      and dominance), and general sense of entitlement. Participants completed a number
      of established self-report measures and a series of computer-based reaction time
      tasks including two implicit association tests, one go/no-go association task,
      and four sentence judgment tasks. Significant group differences emerged across
      all measures both at the explicit and at the implicit level. Most implicit
      measures had very good discriminatory power, and the combination of all implicit
      measures showed excellent discriminatory power, equal to that of the explicit
      measures combined. These findings suggest that some IPV perpetrators hold offense
      supportive cognitions that may have become fairly well established and have
      started to operate at an automatic level. Implicit measures could be useful tools
      for risk assessment purposes and identification of treatment needs alongside
      already established measures.

PMID- 29448910
TI  - Assessing the Mediating Role of Social Support in Childhood Maltreatment and
      Psychopathology Among College Students in Northern Ireland.
AB  - The detrimental impact of early trauma, particularly childhood maltreatment, on
      mental health is well documented. Although it is understood that social support
      can act as a protective factor toward mental health for children who experience
      such adversity, few studies have addressed the experience of childhood
      maltreatment and the important function of social support in adulthood. The
      current study aimed to assess the mediating role of social support in the
      relationship between childhood experiences of maltreatment and mental health
      outcomes including anxiety, depression, posttraumatic stress disorder (PTSD), and
      problematic alcohol use in a sample of university students ( N = 640) from
      Northern Ireland. Results of binary logistic regression analyses indicated that
      those reporting experiences of childhood maltreatment were at increased odds of
      mental health outcomes of PTSD, anxiety, and depression, but not alcohol use.
      Those reporting greater social support were significantly less likely to report
      on these mental health outcomes. In addition, the indirect paths from childhood
      maltreatment through social support to PTSD, depression, and anxiety were all
      significant, suggesting that social support, particularly family support, is a
      significant mediator of these relationships. Such findings have important
      implications for the social care response to children experiencing maltreatment
      and future support for such children as they transition to adolescence and
      adulthood.

PMID- 29448911
TI  - Investigation of the selectivity of one type of small-molecule inhibitor for
      three Nav channel isoforms based on the method of computer simulation.
AB  - Voltage-gated sodium (Nav) channels play a pivotal role for the changes in
      membrane potential and belong to large membrane proteins that compose four
      voltage sensor domains (VSD1-4). In this study we describe the binding mode and
      selectivity of one of the aryl sulfonamide sodium channel inhibitors, PF
      04856264, for the VSD4s in Nav1.4, Nav1.5 and Nav1.7, respectively, through
      molecular dynamics simulation and enhanced post-dynamics analyses. Our results
      show that there are three binding site regions (BSR1-3) in the combination of the
      ligand and receptors, of which BSR1 and BSR3 contribute to the selectivity and
      affinity of the ligand to the receptor. What's more, the 39th residue (Y39 in
      VSD4hNav1.4/ VSD4hNav1.7 and A39 in VSD4hNav1.5) and N42 in BSR1, the 84th
      residue (L84 in VSD4hNav1.4, T84 in VSD4hNav1.5 and M84 in VSD4hNav1.7) in BSR2
      and the conserved positive charged residues in BSR3 have major contributions to
      the interaction between the ligand and receptor. Further analysis reveals that if
      the 39th residue has a benzene ring structure, the connection of BSR1 and the
      ligand would be much stronger through pi-stacking interaction. On the other hand,
      the strength and number of the hydrogen bonds formed by the ligand and the
      conserved arginines on S4 determine the contribution of BSR3 to the total free
      binding energy. We anticipate this study pave the way for the design of more
      effective and safe treatment for pain that selectively target Nav1.7.

PMID- 29448912
TI  - A variant in the SCN10A enhancer may affect human mechanical pain sensitivity.
AB  - Expression of Nav1.8, encoded by SCN10A, can affect pain transmission and thus
      mediate the human pain phenotype. In the current study, we assessed whether the
      variant rs6801957, located in the SCN10A enhancer region, may have the potential
      to affect human pain. Through dual-luciferase reporter assays in 293T cells, we
      found that the SCN10A enhancer A (Enh-A) increased the activity of the SCN10A
      promoter ( P < 0.05). Additionally, in a cohort of 309 healthy women, mutant
      rs6801957 A/A was found to have a significant association with decreased human
      experimental mechanical pain sensitivity ( P < 0.05). We then found that mutant
      genotype A/A suppressed the increased effect of Enh-A compared with wild-type G/G
      ( P < 0.05). The association between rs6801957 and human experimental mechanical
      pain sensitivity was further validated in a larger cohort of 1005 women ( P <
      0.05). In conclusion, these results demonstrated that the variant rs6801957 and
      Enh-A may affect SCN10A gene expression and play an important role in human
      mechanical pain sensitivity.

PMID- 29448915
TI  - Shear Conditioning of Adipose Stem Cells for Reduced Platelet Binding to
      Engineered Vascular Grafts.
AB  - Conferring antithrombogenicity to tissue-engineered vascular grafts remains a
      major challenge, especially for urgent bypass grafting that excludes approaches
      based on expanding autologous endothelial cells (ECs) that requires weeks of cell
      culture. Adipose-derived stem cells (ASCs) are available from most patients in
      sufficient number for coronary bypass graft seeding and may be effective as
      allogeneic cells. We thus compared the adhesion and platelet binding of human
      ASCs that were shear conditioned with constant and pulsatile shear stress (SS)
      after seeding the cells on a biologically engineered matrix suitable for arterial
      grafts. A monolayer of cells was maintained up to 15 dyn/cm2 constant SS and up
      to 15 dyn/cm2 mean pulsatile SS for 6 days of shear flow. Platelet binding was
      reduced from 83% to 6% of surface area and nitric oxide production was increased
      23-fold with 7.5-15 dyn/cm2 constant SS, but not pulsatile SS, relative to cells
      cultured statically on the matrix for 6 days. The reduction in platelet binding
      varied from no reduction to maximum reduction over a constant shear range of ~2
      to 4 dyn/cm2, respectively. Collectively, the study supports the potential use of
      ASCs to seed the luminal surface of a vascular graft made from this biologically
      engineered matrix to confer an antithrombogenic surface during the development of
      an endothelium from the seeded cells or the surrounding blood and tissue.

PMID- 29448916
TI  - Tensioning of the radioscaphocapitate and long radio-lunate ligaments for dynamic
      radiocarpal instability.
AB  - : During 1994-2003, we treated 20 patients with post-traumatic radial-sided wrist
      pain and dynamic radiocarpal instability. After arthroscopy confirmed no
      disruption of the radioscaphocapitate ligament and an increased laxity of the
      ligament, we passed a strip of the radioscaphocapitate ligament through the long
      radio-lunate ligament. The rationale of this procedure was to increase tension of
      the two ligaments and to close the space of Poirier. Eighteen patients were
      assessed after 1-3.7 years (mean 2.5 years). Four patients were symptom-free and
      11 patients were markedly improved. Fourteen patients were followed for 11-15
      years; four patients were symptom-free and eight patients were markedly improved.
      Two reported unchanged symptoms and none was worse in the follow-up. Based on our
      findings, we suggest a cause of post-traumatic radial-sided wrist pain is laxity
      of the radiocarpal joint. We conclude that our surgical procedure increases
      tension in the radioscaphocapitate and long radio-lunate ligaments and decreases
      wrist pain at rest and during activity. LEVEL OF EVIDENCE: IV.

PMID- 29448914
TI  - Quantitative evaluation to efficacy and safety of therapies for psoriasis: A
      network meta-analysis.
AB  - Therapies treating psoriasis can be categorized into five classes according to
      their mechanism: anti-metabolites (AM), anti-interleukin-12/23 agents (anti
      IL12/23), anti-interleukin-17 agents (anti-IL17), anti-T-cell agent (ANT), and
      anti-tumor necrosis factor-alpha agent (anti-TNF-alpha). This network meta
      analysis (NMA) aimed to give a quantitative and systemic evaluation of safety and
      efficacy for the five kinds of therapies mentioned above. Odds ratios and mean
      differences were calculated to evaluate binary and continuous outcomes,
      respectively. Forest plots were conducted to show the performance of pair-wise
      comparison of above therapies in each outcome, and surface under the cumulative
      ranking curves was given to evaluate the relative ranking of above therapies in
      each outcome. Node splitting was conducted to evaluate the consistency between
      direct and indirect evidence. Direct comparisons from 65 studies (32,352
      patients) were included in this NMA. Our results showed an excellent efficacy of
      anti-IL12/23 and anti-IL17. However, these two therapies and anti-TNF-alpha were
      revealed to have a high possibility to cause adverse effects (AEs) such as
      infections. Additionally, node splitting showed that no inconsistency appeared
      between the direct and indirect comparisons. Anti-IL12/23 was the most
      recommended therapy according to this NMA. Anti-IL17 had similar efficacy to anti
      IL12/23 but should be applied with caution since it has poor performance in
      safety outcomes.

PMID- 29448913
TI  - Role of medullary astroglial glutamine synthesis in tooth pulp hypersensitivity
      associated with frequent masseter muscle contraction.
AB  - Background The mechanisms underlying tooth pulp hypersensitivity associated with
      masseter muscle hyperalgesia remain largely underinvestigated. In the present
      study, we aimed to determine whether masseter muscle contraction induced by daily
      electrical stimulation influences the mechanical head-withdrawal threshold and
      genioglossus electromyography activity caused by the application of capsaicin to
      the upper first molar tooth pulp. We further investigated whether astroglial
      glutamine synthesis is involved in first molar tooth pulp hypersensitivity
      associated with masseter muscle contraction. Methods The first molar tooth pulp
      was treated with capsaicin or vehicle in masseter muscle contraction or sham
      rats, following which the astroglial glutamine synthetase inhibitor methionine
      sulfoximine or Phosphate buffered saline (PBS) was applied. Astroglial activation
      was assessed via immunohistochemistry. Results The mechanical head-withdrawal
      threshold of the ipsilateral masseter muscle was significantly decreased in
      masseter muscle contraction rats than in sham rats. Genioglossus electromyography
      activity was significantly higher in masseter muscle contraction rats than sham
      rats. Glial fibrillary acidic protein-immunoreactive cell density was
      significantly higher in masseter muscle contraction rats than in sham rats.
      Administration of methionine sulfoximine induced no significant changes in the
      density of glial fibrillary acidic protein-immunoreactive cells relative to PBS
      treatment. However, mechanical head-withdrawal threshold was significantly higher
      in masseter muscle contraction rats than PBS-treated rats after methionine
      sulfoximine administration. Genioglossus electromyography activity following
      first molar tooth pulp capsaicin treatment was significantly lower in methionine
      sulfoximine-treated rats than in PBS-treated rats. In the ipsilateral region, the
      total number of phosphorylated extracellular signal-regulated protein kinase
      immunoreactive cells in the medullary dorsal horn was significantly smaller upon
      first molar tooth pulp capsaicin application in methionine sulfoximine-treated
      rats than in PBS-treated rats. Conclusions Our results suggest that masseter
      muscle contraction induces astroglial activation, and that this activation
      spreads from caudal to the obex in the medullary dorsal horn, resulting in
      enhanced neuronal excitability associated with astroglial glutamine synthesis in
      medullary dorsal horn neurons receiving inputs from the tooth pulp. These
      findings provide significant insight into the mechanisms underlying tooth pulp
      hypersensitivity associated with masseter muscle contraction.

PMID- 29448917
TI  - A randomized controlled trial comparing ketorolac and triamcinolone injections in
      adults with trigger digits.
AB  - We assessed the efficacy of ketorolac trometamol injections compared with
      triamcinolone acetonide injections in trigger digits. Patients with trigger
      digits were randomized to receive either ketorolac or triamcinolone. They were
      followed up at 3, 6, 12 and 24 weeks, and monitored for resolution of triggering,
      pain and total active motion. One hundred and twenty-one patients with single
      trigger digits were recruited (59 ketorolac, 62 triamcinolone). At 6 weeks, 54%
      of patients in the triamcinolone group had complete resolution of trigger,
      whereas no patients in the ketorolac group had resolution. At 12 weeks, 58% of
      patients in the triamcinolone group had complete resolution of trigger compared
      with 6.7% in the ketorolac group. At 24 weeks, both groups had comparable rates
      of resolution at 26% and 25%, respectively. Patients in the triamcinolone group
      had significantly better resolution of pain at 3, 6 and 12 weeks. But at 24
      weeks, there was no significant difference in pain between both groups.
      Significantly less flexion deformity was reported at 3 weeks and 6 weeks in the
      triamcinolone group. In the short term, ketorolac was less effective in relieving
      symptoms of trigger digit than triamcinolone. Level of evidence: I.

PMID- 29448918
TI  - Improving psychotherapy effectiveness by addressing the problem of premature
      termination: Introduction to a special section.
AB  - Premature termination appears to be a consistent problem in psychotherapy,
      showing up across client, treatment, and therapist types. As psychotherapy
      researchers and practitioners, it is important that we gain a better
      understanding of this negative psychotherapy event and identify methods for
      reducing its occurrence. This article introduces a special section on premature
      termination in psychotherapy. In addition to briefly introducing the articles
      contained in the special section, this article offers suggestions for future
      research on the topic of premature termination.

PMID- 29448919
TI  - Jasmonic acid facilitates flower opening and floral organ development through the
      upregulated expression of SlMYB21 transcription factor in tomato.
AB  - Plants coordinate the timing of flower opening with pollen and gynoecium
      maturation to achieve successful pollination. However, little is known about how
      the coordination is executed. We found that flower bud development was paused
      immediately before flower opening in a jasmonic acid (JA)-insensitive tomato
      mutant, jai1-1. Phytohormone measurement and RNA analysis in flower buds revealed
      that newly synthesised JA peaked at two days before flower opening and the
      expression of a transcription factor gene SlMYB21 delayed in jai1-1. Buds of
      transgenic tomato plants expressing an artificial repressor, AtMYB24-SRDX, which
      was expected to impede the function of SlMYB21, aborted flower opening and
      resembled those of jai1-1. Furthermore, the AtMYB24-SRDX plants produced abnormal
      pollen grains deficient in germination and pistils that did not support pollen
      tube elongation. We concluded that JA facilitates the expression of SlMYB21,
      which coordinates flower opening, pollen maturation, and gynoecium function in
      tomato.

PMID- 29448920
TI  - The T790M resistance mutation in EGFR is only found in cfDNA from erlotinib
      treated NSCLC patients that harbored an activating EGFR mutation before
      treatment.
AB  - BACKGROUND: Lung cancer patients with an activating mutation in the EGFR
      (epidermal growth factor receptor) can develop resistance to erlotinib treatment,
      which is often mediated by the T790M resistance mutation in EGFR. The
      difficulties in obtaining biopsies at progression make it challenging to
      investigate the appearance of the T790M mutation at progression in large patient
      cohorts. We have used cell free DNA (cfDNA) from patients treated with erlotinib
      to investigate if the development of a T790M mutation coincides with the presence
      of an activating EGFR mutation in the pre-treatment blood sample. METHODS: A
      cohort of 227 NSCLC (non-small cell lung cancer) adenocarcinoma patients was
      treated with erlotinib irrespective of EGFR-mutational status. Blood samples were
      drawn immediately before erlotinib treatment was initiated and again at
      progression. The cobas(r) EGFR Mutation Test v2 designed for cfDNA was used to
      identify 42 EGFR mutations. RESULTS: Of the 227 NSCLC patients, blood samples
      were available from 144 patients both before erlotinib treatment and at
      progression (within 1 month before or after clinical progression). One hundred
      and twenty-eight of the 144 were wild-type EGFR before treatment, and we
      demonstrate that the T790M mutation was not present at progression in any of
      these. In contrast, in the 16 patients with an activating EGFR mutation in the
      pre-treatment blood sample six patients (38%) were identified with a T790M
      mutation in the progression blood sample. CONCLUSION: The T790M resistance
      mutation is only found in the cfDNA of erlotinib-treated NSCLC patients if they
      have an activating EGFR mutation before treatment.

PMID- 29448921
TI  - Evaluation of risk factors for perforated peptic ulcer.
AB  - BACKGROUND: The aim of this study was to evaluate the prediction factors for
      perforated peptic ulcer (PPU). METHODS: At St. Luke's International Hospital in
      Tokyo, Japan, a case control study was performed between August 2004 and March
      2016. All patients diagnosed with PPU were included. As control subjects,
      patients with age, sex and date of CT scan corresponding to those of the PPU
      subjects were included in the study at a proportion of 2 controls for every PPU
      subject. All data such as past medical histories, physical findings, and
      laboratory data were collected through chart reviews. Univariate analyses and
      multivariate analyses with logistic regression were conducted, and receiver
      operating characteristic curves (ROCs) were calculated to show validity.
      Sensitivity analyses were performed to confirm results using a stepwise method
      and conditional logistic regression. RESULTS: A total of 408 patients were
      included in this study; 136 were a group of patients with PPU, and 272 were a
      control group. Univariate analysis showed statistical significance in many
      categories. Four different models of multivariate analyses were conducted, and
      significant differences were found for muscular defense and a history of peptic
      ulcer disease (PUD) in all models. The conditional forced-entry analysis of
      muscular defense showed an odds ratio (OR) of 23.8 (95% confidence interval [CI]:
      5.70-100.0), and the analysis of PUD history showed an OR of 6.40 (95% CI: 1.13
      36.2). The sensitivity analysis showed consistent results, with an OR of 23.8
      366.2 for muscular defense and an OR of 3.67-7.81 for PUD history. The area under
      the curve (AUC) of all models was high enough to confirm the results. However,
      anticoagulants, known risk factors for PUD, did not increase the risk for PPU in
      our study. The conditional forced-entry analysis of anticoagulant use showed an
      OR of 0.85 (95% CI: 0.03-22.3). CONCLUSIONS: The evaluation of prediction factors
      and development of a prediction rule for PPU may help our decision making in
      performing a CT scan for patients with acute abdominal pain.

PMID- 29448922
TI  - A randomised control crossover trial of a theory based intervention to improve
      sun-safe and healthy behaviours in construction workers: study protocol.
AB  - BACKGROUND: Exposure to sunlight can have both positive and negative health
      impacts. Excessive exposure to ultra-violet (UV) radiation from the sun can cause
      skin cancer, however insufficient exposure to sunlight has a detrimental effect
      on production of Vitamin D. In the construction industry there are onsite
      proactive behaviours for safety, but sun-safety remains a low priority. There is
      limited research on understanding the barriers to adopting sun-safe behaviours
      and the association this may have with Vitamin D production. This paper reports a
      protocol for an intervention study, using text messaging in combination with a
      supportive smartphone App. The intervention aims to both reduce UV exposure
      during months with higher UV levels and promote appropriate dietary changes to
      boost Vitamin D levels during months with low UV levels. METHOD/DESIGN:
      Approximately 60 construction workers will be recruited across the United
      Kingdom. A randomised control crossover trial (RCCT) will be used to test the
      intervention, with randomisation at site level - i.e. participants will receive
      both the control (no text messages or supportive App support) and intervention
      (daily text messages and supportive App). Using the Theory of Planned Behaviour
      (TPB) the intervention focuses on supporting sun-safety and healthy dietary
      decisions in relation to Vitamin D intake. The intervention emphasises
      cultivating the perception of normative support in the workplace, increasing
      awareness of control and self-efficacy in taking sun-protective behaviours,
      making healthier eating choices to boost Vitamin D, and tackling stigmas attached
      to image and group norms. Each study epoch will last 21 days with intervention
      text messages delivered on workdays only. The supportive App will provide
      supplementary information about sun protective behaviours and healthy dietary
      choices. The primary outcome measure is 25-hydroxy-Vitamin D [25(OH)D] level
      (obtained using blood spot sampling), which will be taken pre and post control
      and intervention periods. Secondary outcome measures are two-fold, (1) using the
      TPB to detect changes in behaviour, and (2) quantifying UV exposure during the UK
      peak radiation season (April-September) using body-mounted UV sensors.
      DISCUSSION: This study will provide important information about the effectiveness
      of a technology-based intervention to promote sun-safety and healthy behaviours
      in outdoor construction workers. TRIAL REGISTRATION: ISRCTN15888934
      retrospectively registered 15.01.2018.

PMID- 29448923
TI  - Data-driven predictions and novel hypotheses about zoonotic tick vectors from the
      genus Ixodes.
AB  - BACKGROUND: With the resurgence of tick-borne diseases such as Lyme disease and
      the emergence of new tick-borne pathogens such as Powassan virus, understanding
      what distinguishes vectors from non-vectors, and predicting undiscovered tick
      vectors is a crucial step towards mitigating disease risk in humans. We aimed to
      identify intrinsic traits that predict which Ixodes tick species are confirmed or
      strongly suspected to be vectors of zoonotic pathogens. METHODS: We focused on
      the well-studied tick genus Ixodes from which many species are known to transmit
      zoonotic diseases to humans. We apply generalized boosted regression to
      interrogate over 90 features for over 240 species of Ixodes ticks to learn what
      intrinsic features distinguish zoonotic vectors from non-vector species. In
      addition to better understanding the biological underpinnings of tick vectorial
      capacity, the model generates a per species probability of being a zoonotic
      vector on the basis of intrinsic biological similarity with known Ixodes vector
      species. RESULTS: Our model predicted vector status with over 91% accuracy, and
      identified 14 Ixodes species with high probabilities (80%) of transmitting
      infections from animal hosts to humans on the basis of their traits.
      Distinguishing characteristics of zoonotic tick vectors of Ixodes tick species
      include several anatomical structures that influence host seeking behavior and
      blood-feeding efficiency from a greater diversity of host species compared to non
      vectors. CONCLUSIONS: Overall, these results suggest that zoonotic tick vectors
      are most likely to be those species where adult females hold a fecundity
      advantage by producing more eggs per clutch, which develop into larvae that feed
      on a greater diversity of host species compared to non-vector species. These
      larvae develop into nymphs whose anatomy are well suited for more efficient and
      longer feeding times on soft-bodied hosts compared to non-vectors, leading to
      larger adult females with greater fecundity. In addition to identifying novel,
      testable hypotheses about intrinsic features driving vectorial capacity across
      Ixodes tick species, our model identifies particular Ixodes species with the
      highest probability of carrying zoonotic diseases, offering specific targets for
      increased zoonotic investigation and surveillance.

PMID- 29448925
TI  - Insecticide resistance evolution with mixtures and sequences: a model-based
      explanation.
AB  - BACKGROUND: Insecticide resistance threatens effective vector control, especially
      for mosquitoes and malaria. To manage resistance, recommended insecticide use
      strategies include mixtures, sequences and rotations. New insecticides are being
      developed and there is an opportunity to develop use strategies that limit the
      evolution of further resistance in the short term. A 2013 review of modelling and
      empirical studies of resistance points to the advantages of mixtures. However,
      there is limited recent, accessible modelling work addressing the evolution of
      resistance under different operational strategies. There is an opportunity to
      improve the level of mechanistic understanding within the operational community
      of how insecticide resistance can be expected to evolve in response to different
      strategies. This paper provides a concise, accessible description of a flexible
      model of the evolution of insecticide resistance. The model is used to develop a
      mechanistic picture of the evolution of insecticide resistance and how it is
      likely to respond to potential insecticide use strategies. The aim is to reach an
      audience unlikely to read a more detailed modelling paper. The model itself, as
      described here, represents two independent genes coding for resistance to two
      insecticides. This allows the representation of the use of insecticides in
      isolation, sequence and mixtures. RESULTS: The model is used to demonstrate the
      evolution of resistance under different scenarios and how this fits with
      intuitive reasoning about selection pressure. Using an insecticide in a mixture,
      relative to alone, always prompts slower evolution of resistance to that
      insecticide. However, when resistance to both insecticides is considered,
      resistance thresholds may be reached later for a sequence relative to a mixture.
      Increasing the ability of insecticides to kill susceptible mosquitoes
      (effectiveness), has the most influence on favouring a mixture over a sequence
      because one highly effective insecticide provides more protection to another in a
      mixture. CONCLUSIONS: The model offers an accessible description of the process
      of insecticide resistance evolution and how it is likely to respond to
      insecticide use. A simple online user-interface allowing further exploration is
      also provided. These tools can contribute to an improved discussion about
      operational decisions in insecticide resistance management.

PMID- 29448924
TI  - H2O2 mediates ALA-induced glutathione and ascorbate accumulation in the
      perception and resistance to oxidative stress in Solanum lycopersicum at low
      temperatures.
AB  - BACKGROUND: Low temperature is a crucial factor influencing plant growth and
      development. The chlorophyll precursor, 5-aminolevulinic acid (ALA) is widely
      used to improve plant cold tolerance. However, the interaction between H2O2 and
      cellular redox signaling involved in ALA-induced resistance to low temperature
      stress in plants remains largely unknown. Here, the roles of ALA in perceiving
      and regulating low temperature-induced oxidative stress in tomato plants,
      together with the roles of H2O2 and cellular redox states, were characterized.
      RESULTS: Low concentrations (10-25 mg.L- 1) of ALA enhanced low temperature
      induced oxidative stress tolerance of tomato seedlings. The most effective
      concentration was 25 mg.L- 1, which markedly increased the ratio of reduced
      glutathione and ascorbate (GSH and AsA), and enhanced the activities of
      superoxide dismutase, catalase, ascorbate peroxidase, dehydroascorbate reductase,
      and glutathione reductase. Furthermore, gene expression of respiratory burst
      oxidase homolog1 and H2O2 content were upregulated with ALA treatment under
      normal conditions. Treatment with exogenous H2O2, GSH, and AsA also induced plant
      tolerance to oxidative stress at low temperatures, while inhibition of GSH and
      AsA syntheses significantly decreased H2O2-induced oxidative stress tolerance.
      Meanwhile, scavenging or inhibition of H2O2 production weakened, but did not
      eliminate, GSH- or AsA- induced tomato plant tolerance to oxidative stress at low
      temperatures. CONCLUSIONS: Appropriate concentrations of ALA alleviated the low
      temperature-induced oxidative stress in tomato plants via an antioxidant system.
      The most effective concentration was 25 mg.L- 1. The results showed that H2O2
      induced by exogenous ALA under normal conditions is crucial and may be the
      initial step for perception and signaling transmission, which then improves the
      ratio of GSH and AsA. GSH and AsA may then interact with H2O2 signaling,
      resulting in enhanced antioxidant capacity in tomato plants at low temperatures.

PMID- 29448926
TI  - Histologic chorioamnionitis in preterm infants: correlation with brain magnetic
      resonance imaging at term equivalent age.
AB  - BACKGROUND: To explore the associations between histologic chorioamnionitis with
      brain injury, maturation and size on magnetic resonance imaging (MRI) of preterm
      infants at term equivalent age. METHODS: Preterm infants (23-36 weeks'
      gestational age) were recruited into two longitudinal cohort studies. Presence or
      absence of chorioamnionitis was obtained from placental histology and clinical
      data were recorded. MRI at term-equivalent age was assessed for brain injury
      (intraventricular haemorrhage, cysts, signal abnormalities), maturation (degree
      of myelination, gyral maturation) and size of cerebral structures (metrics and
      brain segmentation). Histologic chorioamnionitis was assessed as a predictor of
      MRI variables using linear and logistic regression, with adjustment for
      confounding perinatal variables. RESULTS: Two hundred and twelve infants were
      included in this study, 47 (22%) of whom had histologic chorioamnionitis.
      Histologic chorioamnionitis was associated with higher odds of intraventricular
      haemorrhage (odds ratio [OR] (95% confidence interval [CI]) = 7.4 (2.4, 23.1)),
      less mature gyral maturation (OR (95% CI) = 2.0 (1.0, 3.8)) and larger brain
      volume (mean difference in cubic centimeter (95% CI) of 14.1 (1.9, 26.2)); but
      all relationships disappeared following adjustment for perinatal variables.
      CONCLUSION: Histologic chorioamnionitis was not independently associated with
      IVH, less mature gyral maturation or brain volume at term-equivalent age in
      preterm infants.

PMID- 29448927
TI  - Epidemiological characteristics of malaria from control to elimination in Hubei
      Province, China, 2005-2016.
AB  - BACKGROUND: Hubei Province, China, has been operating a malaria elimination
      programme. This study aimed at investigating the epidemiologic characteristics of
      malaria in Hubei Province (2005-2016) to plan resource allocation for malaria
      elimination. METHODS: Data on all malaria cases from 2005 to 2016 in all counties
      of Hubei Province were extracted from a web-based reporting system. The numbers
      of indigenous and imported cases during the disease control (2005-2010) and
      elimination (2011-2016) stages, as well as their spatiotemporal distribution,
      were compared. RESULTS: A total of 8109 malaria cases were reported from 2005 to
      2016 (7270 and 839 cases during the control and elimination stages,
      respectively). Between 2005 and 2010, indigenous malaria cases comprised the
      majority of total cases (7114/7270; 97.9%), and Plasmodium vivax malaria cases
      accounted for most malaria cases (5572/7270; 76.6%). No indigenous malaria cases
      have been reported in Hubei Province since 2013. Imported malaria cases showed a
      gradually increasing trend from 2011 to 2016, Plasmodium falciparum was the
      predominant species in these cases, and the number of counties with imported
      cases increased from 4 in 2005 to 47 in 2016. During the control and elimination
      stages, the most likely spatial clusters for indigenous cases included 13 and 11
      counties, respectively. However, the cluster of indigenous malaria cases has not
      been identified since September 2011. For imported cases, the most likely cluster
      and three secondary clusters during both stages were identified. CONCLUSIONS:
      Hubei Province has made significant achievements in controlling and eliminating
      malaria; however, the region now faces some challenges associated with the
      increasing number and distribution of imported malaria cases. Priorities for
      malaria elimination should include better management of imported malaria cases,
      prevention of secondary malaria transmission, and ensuring the sustainability of
      malaria surveillance.

PMID- 29448928
TI  - Prevalence of adolescent physical activity-related injuries in sports, leisure
      time, and school: the National Physical Activity Behaviour Study for children and
      Adolescents.
AB  - BACKGROUND: The purpose of this study was to investigate the prevalence of
      adolescent physical activity-related injuries in sports club activities, leisure
      time physical activity and school-based physical activity. The secondary aim was
      to investigate the differences in the prevalence of physical activity -related
      injuries between years 2014 and 2016. In addition, we set out to study the
      associations between age, sex and the frequency of physical activity and injury
      prevalence. METHODS: This cross-sectional study is based on the National Physical
      Activity Behaviour Study for Children and Adolescents (LIITU in Finnish)
      conducted in years 2014 and 2016. The subjects completed an online questionnaire
      in the classroom during school hours. A total of 8406 subjects participated in
      the current study. Out of these, 49% were boys and 51% were girls. The
      proportions of 11-, 13-, and 15-year-olds were 35%, 34% and 31%, respectively.
      RESULTS: In the combined data for 2014 and 2016, injury prevalence was higher in
      sports club activities (46%, 95% CI 44.8-47.8) than in leisure time PA (30%, 95%
      CI, 28.5-30.5) or school-based PA (18%, 95% CI, 17.4-19.1). In leisure time PA,
      the injury prevalence was higher than in school-based PA. In all the three
      settings, injury prevalence was higher in 2016 than in 2014. Frequency of PA was
      associated with a higher risk for PA-related injuries in sports clubs and leisure
      time. CONCLUSIONS: With half of the subjects reporting at least one PA-related
      injury during the past year, results indicate that adolescent PA-related injuries
      are a large-scale problem. There is a worrisome rise in injury prevalence in
      recent years. From a public health standpoint, there is an urgent need to invest
      in injury prevention to reverse this trend.

PMID- 29448929
TI  - Cost-effectiveness analysis of a school-based dental caries prevention program
      using fluoridated milk in Bangkok, Thailand.
AB  - BACKGROUND: This study modelled the cost-effectiveness, from a societal
      perspective, of a program that used fluoridated milk to prevent dental caries in
      children who were 6 years old at the beginning of the program, versus non
      intervention, after 6 years. METHODS: After 6 years, children in the milk
      fluoridation program had a significant (34%) reduction in dental caries
      experience compared to those in the comparison community (i.e., received school
      milk without added fluoride) (DMFS: 1.06 vs. 1.60). RESULTS: This improvement was
      achieved with an investment of Thailand Baht (THB) 5,345,048 over 6 years (or THB
      11.88 per child, per year) (1 US$ = THB(2011) 30.0). When comparing the costs of
      the operation of the program and dental treatment in the test community with
      those of the comparison community, the program resulted in a net societal savings
      of THB 8,177,179 (range 18,597,122 to THB 7,920,711) after 6 years. This
      investment would result in 40,500 DMFS avoided in a community with a childhood
      population of 75,000 [DMFS avoided: 75,000 x (- 0.54)]. CONCLUSIONS: While the
      analysis has inherent limitations due to its dependence on a range of
      assumptions, the results suggest that, from a societal perspective, when compared
      with the non-intervention group, the Bangkok Metropolitan Administration
      intervention appeared to be a more cost-efficient option than current standard
      oral health care.

PMID- 29448930
TI  - A prediction study of warfarin individual stable dose after mechanical heart
      valve replacement: adaptive neural-fuzzy inference system prediction.
AB  - BACKGROUND: It's difficult but urgent to achieve the individualized rational
      medication of the warfarin, we aim to predict the individualized warfarin stable
      dose though the artificial intelligent Adaptive neural-fuzzy inference system
      (ANFIS). METHODS: Our retrospective analysis based on a clinical database,
      involving 21,863 patients from 15 Chinese provinces who receive oral warfarin
      after the heart valve replacement. They were allocated into four groups: the
      external validation group (A group), the internal validation group (B group),
      training group (C group) and stratified training group (D group). We used a
      univariate analysis of general linear models(GLM-univariate) to select the input
      variables and construct two prediction models by the ANFIS with the training and
      stratified training group, and then verify models with two validation groups by
      the mean squared error(MSE), mean absolute error(MAE) and the ideal predicted
      percentage. RESULTS: A total of 13,639 eligible patients were selected, including
      1639 in A group, 3000 in B group, 9000 in C group, and 3192 in D group. Nine
      input variables were selected out and two five-layered ANFIS models were built.
      ANFIS model achieved the highest total ideal predicted percentage 63.7%. In the
      dose subgroups, all the models performed best in the intermediate-dose group with
      the ideal predicted percentage 82.4~ 86.4%, and the use of the stratified
      training group slightly increased the prediction accuracy in low-dose group by
      8.8 and 5.2%, respectively. CONCLUSION: As a preliminary attempt, ANFIS model
      predicted the warfarin stable dose properly after heart valve surgery among
      Chinese, and also proved that Chinese need lower anticoagulation intensity INR
      (1.5-2.5) to warfarin by reference to the recommended INR (2.5-3.5) in the
      developed countries.

PMID- 29448931
TI  - Effects of different extracts of curcumin on TPC1 papillary thyroid cancer cell
      line.
AB  - BACKGROUND: The thyroid gland is one of the largest endocrine glands in the body.
      The vast majority of TCs (> 90%) originate from follicular cells and are defined
      as differentiated thyroid cancers (DTC) and the two histological subtypes are the
      papillary TC with its variants and the follicular TC. Curcumin possesses a wide
      variety of biological functions, and thanks to its properties, it has gained
      considerable attention due to its profound medicinal values (Prasad, Gupta,
      Tyagi, and Aggarwal, Biotechnol Adv 32:1053-1064, 2014). We have undertaken the
      present work in order to define the possible role of curcumin in modulating the
      genetic expression of cell markers and to understand the effectiveness of this
      nutraceutical in modulating the regression of cancer phenotype. METHODS: As a
      template we used the TPC-1 cells treated with the different extracts of turmeric,
      and examined the levels of expression of different markers (proliferative,
      inflammatory, antioxidant, apoptotic). RESULTS: Treatment with the three
      different curcumin extracts displays anti-inflammatory, antioxidant properties
      and it is able to influence cell cycle with slightly different effects upon the
      extracts. Furthermore curcumin is able to influence cell metabolic activity
      vitality. CONCLUSIONS: In conclusion curcumin has the potential to be developed
      as a safe therapeutic but further studies are needed to verify its antitumor
      ability in vivo.

PMID- 29448932
TI  - Interference competition as a key determinant for spatial distribution of
      mangrove crabs.
AB  - BACKGROUND: The spatial distribution of mangrove crabs has been commonly
      associated with tree zonation and abiotic factors such as ground temperature and
      soil granulometry. Conversely, no studies were designed to investigate the role
      of competition for resources and predation in shaping crab distribution in
      mangroves, despite these biotic factors are recognised as key determinants for
      spatial patterns observed in the communities colonising rocky and sandy
      intertidal habitats.We studied floral and faunal assemblages in two zones of a
      Sri Lankan mangrove, a man-made upper intertidal level and a natural eulittoral,
      mid-shore one. Leaf choice experiments were designed to study both feeding rate
      and intra and inter-specific interactions for food of sesarmid crabs in the two
      habitats in order to better understand crab spatial distribution. RESULTS: The
      two intertidal belts differed in terms of floral composition and crab species
      abundance. The eulittoral zone was strongly dominated by Neosarmatium smithi,
      while within the elevated littoral fringe four sesarmids (N. smithi, N.
      asiaticum, N. malabaricum and Muradium tetragonum) were more evenly distributed.
      At both levels, all sesarmids showed to collect significantly more Bruguiera spp.
      and Rhizophora apiculata leaves than Excoecaria agallocha ones. There was no
      temporal segregation in feeding activity among the four species, resulting in a
      high interference competition for leaves. Regardless of the habitat, N. smithi
      was always successful in winning inter-specific fights. CONCLUSIONS: Our results
      showed that the elevated littoral fringe was more crowded with crabs, but was
      less favourable in terms of food availability and environmental conditions. The
      dominance of N. smithi in gathering mangrove leaves suggests that this species
      may segregate the other sesarmids into less favourable habitats. The present data
      strongly suggest for the first time that interference competition for food can
      contribute to shape mangrove crab spatial distribution.

PMID- 29448933
TI  - The curious case of vacuolar ATPase: regulation of signaling pathways.
AB  - The Vacuolar ATPase (V-ATPase) is a proton pump responsible for controlling the
      intracellular and extracellular pH of cells. The structure of V-ATPase has been
      highly conserved among all eukaryotic cells and is involved in diverse functions
      across species. V-ATPase is best known for its acidification of endosomes and
      lysosomes and is also important for luminal acidification of specialized cells.
      Several reports have suggested the involvement of V-ATPase in maintaining an
      alkaline intracellular and acidic extracellular pH thereby aiding in
      proliferation and metastasis of cancer cells respectively. Increased expression
      of V-ATPase and relocation to the plasma membrane aids in cancer modulates key
      tumorigenic cell processes like autophagy, Warburg effect, immunomoduation, drug
      resistance and most importantly cancer cell signaling. In this review, we discuss
      the direct role of V-ATPase in acidification and indirect regulation of signaling
      pathways, particularly Notch Signaling.

PMID- 29448934
TI  - From theoretical concepts to policies and applied programmes: the landscape of
      integration of oral health in primary care.
AB  - BACKGROUND: Despite its importance, the integration of oral health into primary
      care is still an emerging practice in the field of health care services. This
      scoping review aims to map the literature and provide a summary on the conceptual
      frameworks, policies and programs related to this concept. METHODS: Using the
      Levac et al. six-stage framework, we performed a systematic search of electronic
      databases, organizational websites and grey literature from 1978 to April 2016.
      All relevant original publications with a focus on the integration of oral health
      into primary care were retrieved. Content analyses were performed to synthesize
      the results. RESULTS: From a total of 1619 citations, 67 publications were
      included in the review. Two conceptual frameworks were identified. Policies
      regarding oral heath integration into primary care were mostly oriented toward
      common risk factors approach and care coordination processes. In general, oral
      health integrated care programs were designed in the public health sector and
      based on partnerships with various private and public health organizations,
      governmental bodies and academic institutions. These programmes used various
      strategies to empower oral health integrated care, including building
      interdisciplinary networks, training non-dental care providers, oral health
      champion modelling, enabling care linkages and care coordinated process, as well
      as the use of e-health technologies. The majority of studies on the programs
      outcomes were descriptive in nature without reporting long-term outcomes.
      CONCLUSIONS: This scoping review provided a comprehensive overview on the concept
      of integration of oral health in primary care. The findings identified major gaps
      in reported programs outcomes mainly because of the lack of related research.
      However, the results could be considered as a first step in the development of
      health care policies that support collaborative practices and patient-centred
      care in the field of primary care sector.

PMID- 29448935
TI  - Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are
      infrequent in familial colorectal cancer and polyposis.
AB  - Germline mutations in BUB1 and BUB3 have been reported to increase the risk of
      developing colorectal cancer (CRC) at young age, in presence of variegated
      aneuploidy and reminiscent dysmorphic traits of mosaic variegated aneuploidy
      syndrome. We performed a mutational analysis of BUB1 and BUB3 in 456
      uncharacterized mismatch repair-proficient hereditary non-polyposis CRC families
      and 88 polyposis cases. Four novel or rare germline variants, one splice-site and
      three missense, were identified in four families. Neither variegated aneuploidy
      nor dysmorphic traits were observed in carriers. Evident functional effects in
      the heterozygous form were observed for c.1965-1G>A, but not for c.2296G>A
      (p.E766K), in spite of the positive co-segregation in the family. BUB1 c.2473C>T
      (p.P825S) and BUB3 c.77C>T (p.T26I) remained as variants of uncertain
      significance. As of today, the rarity of functionally relevant mutations
      identified in familial and/or early onset series does not support the inclusion
      of BUB1 and BUB3 testing in routine genetic diagnostics of familial CRC.

PMID- 29448936
TI  - Chitinase-3-like 1 is a biomarker of acute kidney injury and mortality in
      paediatric severe malaria.
AB  - BACKGROUND: Chitinase-3-like 1 (CHI3L1) is a glycoprotein elevated in paediatric
      severe malaria, and an emerging urinary biomarker of acute kidney injury (AKI).
      Based on the hypothesis that elevated CHI3L1 levels in malaria are associated
      with disease severity, the relationship between plasma CHI3L1 levels, AKI and
      mortality was investigated in Ugandan children enrolled in a clinical trial
      evaluating inhaled nitric oxide (iNO) as an adjunctive therapy for severe
      malaria. METHODS: Plasma CHI3L1 levels were measured daily for 4 days in children
      admitted to hospital with severe malaria and at day 14 follow up. AKI was defined
      using the Kidney Disease: Improving Global Outcomes consensus criteria. This is a
      secondary analysis of a randomized double-blind placebo-controlled trial of iNO
      versus placebo as an adjunctive therapy for severe malaria. Inclusion criteria
      were: age 1-10 years, and selected criteria for severe malaria. Exclusion
      criteria included suspected bacterial meningitis, known chronic illness including
      renal disease, haemoglobinopathy, or severe malnutrition. iNO was administered by
      non-rebreather mask for up to 72 h at 80 ppm. RESULTS: CHI3L1 was elevated in
      patients with AKI and remained higher over hospitalization (p < 0.0001).
      Admission CHI3L1 levels were elevated in children who died. By multivariable
      analysis logCHI3L1 levels were associated with increased risk of in-hospital
      death (relative risk, 95% CI 4.10, 1.32-12.75, p = 0.015) and all-cause 6 month
      mortality (3.21, 1.47-6.98, p = 0.003) following correction for iNO and AKI.
      Treatment with iNO was associated with delayed CHI3L1 recovery with a daily
      decline of 34% in the placebo group versus 29% in the iNO group (p = 0.012).
      CHI3L1 levels correlated with markers of inflammation (CRP, sTREM-1, CXCL10),
      endothelial activation (Ang-2, sICAM-1) and intravascular haemolysis (LDH, haem,
      haemopexin). CONCLUSIONS: CHI3L1 is a novel biomarker of malaria-associated AKI
      and an independent risk factor for mortality that is associated with well
      established pathways of severe malaria pathogenesis including inflammation,
      endothelial activation, and haemolysis. Trial registration Clinicaltrials.gov,
      NCT01255215. Registered December 7th 2010.

PMID- 29448937
TI  - Engineering chimeric antigen receptor-T cells for cancer treatment.
AB  - Intratumor heterogeneity of tumor clones and an immunosuppressive
      microenvironment in cancer ecosystems contribute to inherent difficulties for
      tumor treatment. Recently, chimeric antigen receptor (CAR) T-cell therapy has
      been successfully applied in the treatment of B-cell malignancies, underscoring
      its great potential in antitumor therapy. However, functional challenges of CAR-T
      cell therapy, especially in solid tumors, remain. Here, we describe cancer
      immunity phenotypes from a clonal-stromal-immune perspective and elucidate
      mechanisms of T-cell exhaustion that contribute to tumor immune evasion. Then we
      assess the functional challenges of CAR-T cell therapy, including cell
      trafficking and infiltration, targeted-recognition and killing of tumor cells, T
      cell proliferation and persistence, immunosuppressive microenvironment and self
      control regulation. Finally, we delineate tumor precision informatics and
      advancements in engineered CAR-T cells to counteract inherent challenges of the
      CAR-T cell therapy, either alone or in combination with traditional therapeutics,
      and highlight the therapeutic potential of this approach in future tumor
      precision treatment.

PMID- 29448938
TI  - Comparative genomic analysis of ten clinical Streptococcus pneumoniae collected
      from a Malaysian hospital reveal 31 new unique drug-resistant SNPs using whole
      genome sequencing.
AB  - BACKGROUND: Streptococcus pneumoniae or pneumococcus is a leading cause of
      morbidity and mortality worldwide, specifically in relation to community-acquired
      pneumonia. Due to the overuse of antibiotics, S. pneumoniae has developed a high
      degree of resistance to a wide range of antibacterial drugs. METHODS: In this
      study, whole genome sequencing (WGS) was performed for 10 clinical strains of S.
      pneumoniae with different levels of sensitivity to standard antibiotics. The main
      objective was to investigate genetic changes associated with antibiotic
      resistance in S. pneumoniae. RESULTS: Our results showed that resistant isolates
      contain a higher number of non-synonymous single nucleotide polymorphisms (SNPs)
      as compared to susceptible isolates. We were able to identify SNPs that alter a
      single amino acid in many genes involved in virulence and capsular polysaccharide
      synthesis. In addition, 90 SNPs were only presented in the resistant isolates,
      and 31 SNPs were unique and had not been previously reported, suggesting that
      these unique SNPs could play a key role in altering the level of resistance to
      different antibiotics. CONCLUSION: Whole genome sequencing is a powerful tool for
      comparing the full genome of multiple isolates, especially those closely related,
      and for analysing the variations found within antibiotic resistance genes that
      lead to differences in antibiotic sensitivity. We were able to identify specific
      mutations within virulence genes related to resistant isolates. These findings
      could provide insights into understanding the role of single nucleotide mutants
      in conferring drug resistance.

PMID- 29448939
TI  - EXPOsOMICS: final policy workshop and stakeholder consultation.
AB  - The final meeting of the EXPOsOMICS project "Final Policy Workshop and
      Stakeholder Consultation" took place 28-29 March 2017 to present the main results
      of the project and discuss their implications both for future research and for
      regulatory and policy activities. This paper summarizes presentations and
      discussions at the meeting related with the main results and advances in exposome
      research achieved through the EXPOsOMICS project; on other parallel research
      initiatives on the study of the exposome in Europe and in the United States and
      their complementarity to EXPOsOMICS; lessons learned from these early studies on
      the exposome and how they may shape the future of research on environmental
      exposure assessment; and finally the broader implications of exposome research
      for risk assessment and policy development on environmental exposures. The main
      results of EXPOsOMICS in relation to studies of the external exposome and
      internal exposome in relation to both air pollution and water contaminants were
      presented as well as new technologies for environmental health research
      (adductomics) and advances in statistical methods. Although exposome research
      strengthens the scientific basis for policy development, there is a need in terms
      of showing added value for public health to: improve communication of research
      results to non-scientific audiences; target research to the broader landscape of
      societal challenges; and draw applicable conclusions. Priorities for future work
      include the development and standardization of methodologies and technologies for
      assessing the external and internal exposome, improved data sharing and
      integration, and the demonstration of the added value of exposome science over
      conventional approaches in answering priority policy questions.

PMID- 29448940
TI  - Comparative analysis of alfalfa (Medicago sativa L.) leaf transcriptomes reveals
      genotype-specific salt tolerance mechanisms.
AB  - BACKGROUND: Soil salinity is an important factor affecting growth, development,
      and productivity of almost all land plants, including the forage crop alfalfa
      (Medicago sativa). However, little is known about how alfalfa responds and adapts
      to salt stress, particularly among different salt-tolerant cultivars. RESULTS:
      Among seven alfalfa cultivars, we found that Zhongmu-1 (ZM) is relatively salt
      tolerant and Xingjiang Daye (XJ) is salt-sensitive. Compared to XJ, ZM showed
      slower growth under low-salt conditions, but exhibited stronger tolerance to salt
      stress. RNA-seq analysis revealed 2237 and 1125 differentially expressed genes
      (DEGs) between ZM and XJ in the presence and absence of salt stress, among which
      many genes are involved in stress-related pathways. After salt treatment,
      compared with the controls, the number of DEGs in XJ (19373) was about four times
      of that in ZM (4833). We also detected specific differential gene expression
      patterns: In response to salt stress, compared with XJ, ZM maintained relatively
      more stable expression levels of genes related to the ROS and Ca2+ pathways,
      phytohormone biosynthesis, and Na+/K+ transport. Notably, several salt resistance
      associated genes always showed greater levels of expression in ZM than in XJ,
      including a transcription factor. Consistent with the suppression of plant growth
      resulting from salt stress, the expression of numerous photosynthesis- and growth
      hormone-related genes decreased more dramatically in XJ than in ZM. By contrast,
      the expression levels of photosynthetic genes were lower in ZM under low-salt
      conditions. CONCLUSIONS: Compared with XJ, ZM is a salt-tolerant alfalfa cultivar
      possessing specific regulatory mechanisms conferring exceptional salt tolerance,
      likely by maintaining high transcript levels of abiotic and biotic stress
      resistance-related genes. Our results suggest that maintaining this specific
      physiological status and/or plant adaptation to salt stress most likely arises by
      inhibition of plant growth in ZM through plant hormone interactions. This study
      identifies new candidate genes that may regulate alfalfa tolerance to salt stress
      and increases the understanding of the genetic basis for salt tolerance.

PMID- 29448941
TI  - Traditional healing practices in rural Bangladesh: a qualitative investigation.
AB  - BACKGROUND: Traditional healing practice is an important and integral part of
      healthcare systems in almost all countries of the world. Very few studies have
      addressed the holistic scenario of traditional healing practices in Bangladesh,
      although these serve around 80% of the ailing people. This study explored
      distinctive forms of traditional healing practices in rural Bangladesh. METHODS:
      During July to October 2007, the study team conducted 64 unstructured interviews,
      and 18 key informant interviews with traditional healers and patients from
      Bhabanipur and Jobra, two adjacent villages in Chittagong district, Bangladesh.
      The study also used participatory observations of traditional healing activities
      in the treatment centers. RESULTS: Majority of the community members, especially
      people of low socioeconomic status, first approached the traditional healers with
      their medical problems. Only after failure of such treatment did they move to
      qualified physicians for modern treatment. Interestingly, if this failed, they
      returned to the traditional healers. This study identified both religious and non
      religious healing practices. The key religious healing practices reportedly
      included Kalami, Bhandai, and Spiritual Healing, whereas the non-religious
      healing practices included Sorcery, Kabiraji, and Home Medicine. Both patients
      and healers practiced self-medication at home with their indigenous knowledge.
      Kabiraji was widely practiced based on informal use of local medicinal plants in
      rural areas. Healers in both Kalami and Bhandari practices resorted to religious
      rituals, and usually used verses of holy books in healing, which required a firm
      belief of patients for the treatment to be effective. Sorcerers deliberately used
      their so-called supernatural power not only to treat a patient but also to cause
      harm to others upon secret request. The spiritual healing reportedly diagnosed
      and cured the health problems through communication with sacred spirits. Although
      the fee for diagnosis was small, spiritual healing required different types of
      treatment instruments, which made the treatment implicitly expensive.
      CONCLUSIONS: Traditional healing was widely practiced as the means of primary
      healthcare in rural areas of Bangladesh, especially among the people with low
      socioeconomic status. The extent of services showed no decline with the
      advancement of modern medical sciences; rather it has increased with the passage
      of time.

PMID- 29448942
TI  - Cold exposure induced oxidative stress and apoptosis in the myocardium by
      inhibiting the Nrf2-Keap1 signaling pathway.
AB  - BACKGROUND: Exposure to cold weather is associated with infaust cardiovascular
      responses, including myocardial infarction and arrhythmias. However, the exact
      mechanisms of these adverse changes in the myocardium under cold stress are
      unknown. This study was designed to investigate the mechanisms of cardiac injury
      induced by cold stress in mice. METHODS: The mice were randomly divided into
      three groups, normal control (no handling), 1-week cold stress and 2-week cold
      stress. We observed physiological changes of the mice and morphological changes
      of myocardium tissues, and we measured the changes of 3'-nitrotyrosine and 4
      hydroxynonenal, the expression levels of superoxide dismutase-1, superoxide
      dismutase-2, Bax, Bad, Bcl-2, Nuclear factor erythroid-derived 2-like 2 (Nrf2)
      and Kelch like-ECH-associated protein 1 (Keap1) in myocardium by western blot.
      Besides, we detected mRNA of superoxide dismutase-1, superoxide dismutase-2, Bax,
      Bad, Bcl-2, Nrf2 and Keap1 by real-time PCR. One-way analysis of variance,
      followed by LSD-t test, was used to compare each variable for differences among
      the groups. RESULTS: Echocardiography analyses demonstrated left ventricle
      dysfunction in the groups receiving cold stress. Histological analyses witnessed
      inflammation, vacuolar and eosinophilic degeneration occurred in left ventricle
      tissues. Western blotting results showed increased 3'-nitrotyrosine and 4
      hydroxynonenal and decreased antioxidant enzymes (superoxide dismutase-1 and
      superoxide dismutase-2) in the myocardium. Expression of Nrf2 and Keap1 followed
      a downward trend under cold exposure, as indicated by western blotting and real
      time PCR. Expression of anti-apoptotic protein Bcl-2 also showed the same trend.
      In contrast, expression of pro-apoptotic proteins Bax and Bad followed an upward
      trend under cold exposure. The results of real-time PCR were consistent with
      those of western blotting. CONCLUSIONS: These findings were very significant,
      showing that cold exposure induced cardiac injury by inhibiting the Nrf2-Keap1
      signaling pathway.

PMID- 29448943
TI  - Cloning and expression of the sucrose phosphorylase gene in Bacillus subtilis and
      synthesis of kojibiose using the recombinant enzyme.
AB  - BACKGROUND: Kojibiose as a prebiotic and inhibitor of alpha-glucosidase exhibits
      potential for a wide range of applications in the food and medicine fields;
      however, large-scale separation and extraction of kojibiose from nature is
      difficult. Sucrose phosphorylase (SPase) can be used for the production of
      kojibiose, and currently, SPase is only heterologously expressed in E. coli,
      making it unsuitable for use in the food industry. However, Bacillus subtilis is
      generally considered to be a safe organism potentially useful for SPase
      expression. RESULTS: Here, for the first time, we heterologously expressed
      Bifidobacterium adolescentis SPase in a food-grade B. subtilis strain. The
      results showed that SPase was efficiently secreted into the extracellular medium
      in the absence of a signal peptide. After culturing the recombinant strain in a 3
      L bioreactor, crude SPase yield and activity reached 7.5 g/L and 5.3 U/mL,
      respectively, the highest levels reported to date. The optimal reaction
      conditions for kojibiose synthesis catalyzed by recombinant SPase were as
      follows: 0.5 M sucrose, 0.5 M glucose, 0.02 Uenzyme/mgall_substrates, pH 7.0, 50 
      degrees C, and 30 h. Furthermore, the substrate-conversion rate reached 40.01%,
      with kojibiose accounting for 104.45 g/L and selectivity for kojibiose production
      at 97%. CONCLUSIONS: Here, we successfully expressed SPase in B. subtilis in the
      absence of a signal peptide and demonstrated its secretion into the extracellular
      medium. Our results indicated high levels of recombinant enzyme expression, with
      a substrate-conversion rate of 40.01%. These results provide a basis for large
      scale preparation of kojibiose by the recombinant SPase.

PMID- 29448944
TI  - Second-line treatment for advanced NSCLC without actionable mutations: is
      immunotherapy the 'panacea' for all patients?
AB  - The therapeutic approach for the second-line treatment of patients with advanced
      non-small cell lung cancer (NSCLC) without actionable mutations has been
      revolutionized by the recent approval of new effective drugs with various
      mechanisms of action, including nintedanib, ramucirumab, nivolumab,
      pembrolizumab, atezolizumab, and afatinib. The recent network meta-analysis of
      Crequit et al. (BMC Medicine, 15:193, 2017) compared the effectiveness and
      tolerability of the second-line treatments for advanced NSCLC with wild-type or
      unknown status for EGFR. The authors found that immunotherapy might be more
      efficacious than the currently recommended treatments. However, their meta
      analysis does not take into account the role of predictive biomarkers - this is
      indeed a crucial point in the decision-making process considering that only a
      fraction of advanced NSCLC patients might derive a long-term benefit from second
      line immunotherapy. The identification of molecular biomarkers that can predict a
      response to immune checkpoints, angiogenesis, and EGFR inhibitors remains an
      important goal of clinical research in order to maximize the benefit of these
      agents and to aid clinicians in the decision-making process.Please see related
      article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0954
      x.

PMID- 29448946
TI  - Correction to: High density marker panels, SNPs prioritizing and accuracy of
      genomic selection.
AB  - CORRECTION TO: BMC GENETICS (2018) 19:4 DOI: 10.1186/S12863-017-0595-2: The
      original version of this article [1], published on 5 January 2018, contained 3
      formatting errors. In this Correction the affected parts of the article are
      shown. The original article has been updated.

PMID- 29448945
TI  - RNA secondary structure profiling in zebrafish reveals unique regulatory
      features.
AB  - BACKGROUND: RNA is known to play diverse roles in gene regulation. The clues for
      this regulatory function of RNA are embedded in its ability to fold into
      intricate secondary and tertiary structure. RESULTS: We report the transcriptome
      wide RNA secondary structure in zebrafish at single nucleotide resolution using
      Parallel Analysis of RNA Structure (PARS). This study provides the secondary
      structure map of zebrafish coding and non-coding RNAs. The single nucleotide
      pairing probabilities of 54,083 distinct transcripts in the zebrafish genome were
      documented. We identified RNA secondary structural features embedded in
      functional units of zebrafish mRNAs. Translation start and stop sites were
      demarcated by weak structural signals. The coding regions were characterized by
      the three-nucleotide periodicity of secondary structure and display a codon base
      specific structural constrain. The splice sites of transcripts were also
      delineated by distinct signature signals. Relatively higher structural signals
      were observed at 3' Untranslated Regions (UTRs) compared to Coding DNA Sequence
      (CDS) and 5' UTRs. The 3' ends of transcripts were also marked by unique
      structure signals. Secondary structural signals in long non-coding RNAs were also
      explored to better understand their molecular function. CONCLUSIONS: Our study
      presents the first PARS-enabled transcriptome-wide secondary structure map of
      zebrafish, which documents pairing probability of RNA at single nucleotide
      precision. Our findings open avenues for exploring structural features in
      zebrafish RNAs and their influence on gene expression.

PMID- 29448947
TI  - Contradictory and weak evidence on the effectiveness of anti-emetics for MTX
      intolerance in JIA-patients.

PMID- 29448948
TI  - Occupational exposure to HIV in a developing country: assessing knowledge and
      attitude of healthcare professional before and after an awareness symposium.
AB  - OBJECTIVE: Health care providers (HCPs) are at risk of occupational exposure to
      HIV infection. In developing world these exposure occur due to general lack of
      awareness, education and structured training of HCPs. The objective of the study
      was to asses if continuing medical education symposium can be used as an
      effective educational tool to improve attitude, awareness and knowledge regarding
      occupational exposure to HIV infection. This quasi-experimental study was
      conducted among HCPs from Karachi, Pakistan. After assessing the baseline
      knowledge, awareness, and attitude by means of pretest; HCPs were reassessed with
      posttest after an education symposium on occupational exposure to HIV infection.
      RESULTS: Among 364 participating HCPs, 14.2% had previous training on post
      exposure prophylaxis. There was an overall statistically significant (P value <
      0.001) improvement in the attitude of the participants. A statistically positive
      improvement in the number of participants giving correct answer was observed in 9
      out of 11 questions (P value < 0.001). The mean score of participants' knowledge
      before intervention was 6.44 +/- 1.84, which improved to 8.82 +/- 2.17. Along
      with the increase in knowledge, a positive change in the attitude regarding
      safety against HIV was observed after the education symposium.

PMID- 29448949
TI  - A standardized framework for representation of ancestry data in genomics studies,
      with application to the NHGRI-EBI GWAS Catalog.
AB  - The accurate description of ancestry is essential to interpret, access, and
      integrate human genomics data, and to ensure that these benefit individuals from
      all ancestral backgrounds. However, there are no established guidelines for the
      representation of ancestry information. Here we describe a framework for the
      accurate and standardized description of sample ancestry, and validate it by
      application to the NHGRI-EBI GWAS Catalog. We confirm known biases and gaps in
      diversity, and find that African and Hispanic or Latin American ancestry
      populations contribute a disproportionately high number of associations. It is
      our hope that widespread adoption of this framework will lead to improved
      analysis, interpretation, and integration of human genomics data.

PMID- 29448950
TI  - Identification and characterization of microRNA in the lung tissue of pigs with
      different susceptibilities to PCV2 infection.
AB  - Porcine circovirus type 2 (PCV2) is the primary cause of post-weaning
      multisystemic wasting syndrome (PMWS) and other PCV-associated diseases.
      According to our previous RNA-sequencing analysis, the differences in the
      susceptibility to PCV2 infection depended on the genetic differences between the
      Laiwu (LW) and Yorkshire * Landrace crossbred (YL) pigs, but the cellular
      microRNA (miRNA) that are differentially expressed between the LW and YL pigs
      before and after PCV2 infection remain to be determined. In this study, high
      throughput sequencing was performed to determine the abundance and differential
      expression of miRNA in lung tissues from PCV2-infected and PCV2-uninfected LW and
      YL pigs. In total, 295 known and 95 novel miRNA were identified, and 23 known and
      25 novel miRNA were significantly differentially expressed in the PCV2-infected
      vs. PCV2-uninfected LW pigs and/or the PCV2-infected vs. PCV2-uninfected YL pigs.
      The expression levels of ssc-miR-122, ssc-miR-192, ssc-miR-451, ssc-miR-486, and
      ssc-miR-504 were confirmed by quantitative real-time PCR (qRT-PCR). Analysis of
      the potential targets of the four up-regulated miRNA (i.e., ssc-miR-122, ssc-miR
      192, ssc-miR-451 and ssc-miR-486) identified pathways and genes that may be
      important for disease resistance. Among the up-regulated miRNA, ssc-miR-122 can
      repress the protein expression and viral DNA replication of PCV2 and down
      regulate the expression of the nuclear factor of activated T-cells 5 (NFAT5) and
      aminopeptidase puromycin sensitive (NPEPPS) by binding to their 3' untranslated
      region (3'UTR) in PK15 cells. Therefore, ssc-miR-122 may indirectly suppress PCV2
      infection by targeting genes related to the host immune system, such as NFAT5 and
      NPEPPS.

PMID- 29448951
TI  - T-ARMS PCR genotyping of SNP rs445709131 using thermostable strand displacement
      polymerase.
AB  - OBJECTIVES: In a recent publication, we reported the successful use of tetra
      primer-amplification refractory mutation system based polymerase chain reaction
      (T-ARMS-PCR) for genotyping of rs445709131-SNP responsible for the bovine
      leukocyte adhesion deficiency (BLAD) in cattle. The SNP is characterized by
      higher GC content of the surrounding region, hence, the previous protocol
      utilized dimethyl sulfoxide as PCR enhancer. Here, the reaction cocktail was
      modified with the use of thermostable strand displacement polymerase (SD
      polymerase) instead of commonly used Taq DNA Polymerase. The amplification
      efficiency, reaction sensitivity, specificity, and need of PCR enhancer in
      reactions containing SD polymerase and Taq polymerase were compared. RESULTS: T
      ARMS-PCR assay is influenced by multiple factors for the correct genotyping
      necessitating extensive optimization at the initial stages. The described
      modification enabled generation of all amplicons by 25 cycles whereas the assay
      with Taq polymerase needed a minimum of 35 cycles. The modified assay amplified
      all amplicons at a wider range of annealing temperature (50-60  degrees C),
      without the addition of dimethyl sulfoxide. The replacement of Taq polymerase
      with SD polymerase may be beneficial in the T-ARMS assay for development of user
      friendly, faster assay which is less affected by the reaction and cyclic
      conditions.

PMID- 29448952
TI  - A survey of workplace violence against physicians in the hospitals, Myanmar.
AB  - OBJECTIVE: Workplace violence in hospitals is recently becoming a major global
      concern in many countries. However, in Myanmar, we have felt that patients and
      their families have rarely made unreasonable complaints in hospitals, and then,
      the purpose of this study is to report the current state of workplace violence in
      hospitals in Myanmar. Participants are 196 physicians (108 males and 88 females)
      in hospitals in Myanmar. RESULTS: A descriptive survey was conducted in regard to
      verbal abuse and physical violence from patients or the people concerned. At the
      results of this study, the percentages of physicians who have encountered verbal
      abuse and those who have encountered physical violence are markedly low (8.7 and
      1.0%, respectively). The present study is the first to report the frequencies of
      verbal abuse and physical violence against physicians in a least developed
      country, and the results of the present study are important in terms of
      discussing workplace violence in hospitals.

PMID- 29448953
TI  - Clinical prevalence of Lewy body dementia.
AB  - BACKGROUND: The prevalence of dementia with Lewy bodies (DLB) and dementia in
      Parkinson's disease (PDD) in routine clinical practice is unclear. Prevalence
      rates observed in clinical and population-based cohorts and neuropathological
      studies vary greatly. Small sample sizes and methodological factors in these
      studies limit generalisability to clinical practice. METHODS: We investigated
      prevalence in a case series across nine secondary care services over an 18-month
      period, to determine how commonly DLB and PDD cases are diagnosed and reviewed
      within two regions of the UK. RESULTS: Patients with DLB comprised 4.6% (95% CI
      4.0-5.2%) of all dementia cases. DLB was represented in a significantly higher
      proportion of dementia cases in services in the North East (5.6%) than those in
      East Anglia (3.3%; chi2 = 13.6, p < 0.01). DLB prevalence in individual services
      ranged from 2.4 to 5.9%. PDD comprised 9.7% (95% CI 8.3-11.1%) of Parkinson's
      disease cases. No significant variation in PDD prevalence was observed between
      regions or between services. CONCLUSIONS: We found that the frequency of clinical
      diagnosis of DLB varied between geographical regions in the UK, and that the
      prevalence of both DLB and PDD was much lower than would be expected in this case
      series, suggesting considerable under-diagnosis of both disorders. The
      significant variation in DLB diagnostic rates between these two regions may
      reflect true differences in disease prevalence, but more likely differences in
      diagnostic practice. The systematic introduction of more standardised diagnostic
      practice could improve the rates of diagnosis of both conditions.

PMID- 29448955
TI  - Analysis of the genetic diversity and mRNA expression level in porcine
      reproductive and respiratory syndrome virus vaccinated pigs that developed short
      or long viremias after challenge.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSv) infection alters the
      host's cellular and humoral immune response. Immunity against PRRSv is multigenic
      and vary between individuals. The aim of the present study was to compare several
      genes that encode for molecules involved in the immune response between two
      groups of vaccinated pigs that experienced short or long viremic periods after
      PRRSv challenge. These analyses include the sequencing of four SLA Class I, two
      Class II allele groups, and CD163, plus the analysis by quantitative realtime qRT
      PCR of the constitutive expression of TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 mRNA
      and other molecules in peripheral blood mononuclear cells.

PMID- 29448954
TI  - New therapeutic strategies to treat human cancers expressing mutant p53 proteins.
AB  - The tumor suppressor p53 plays a critical role to preserve DNA fidelity from
      diverse insults through the regulation of cell-cycle checkpoints, DNA repair,
      senescence and apoptosis. The TP53 is the most frequently inactivated gene in
      human cancers. This leads to the production of mutant p53 proteins that loose
      wild-type p53 tumor suppression functions and concomitantly acquire new oncogenic
      properties among which deregulated cell proliferation, increased chemoresistance,
      disruption of tissue architecture, promotion of migration, invasion and
      metastasis and several other pro-oncogenic activities. Mouse models show that the
      genetic reconstitution of the wild type p53 tumor suppression functions rescues
      tumor growth. This strongly supports the notion that either restoring wt-p53
      activity or inhibiting mutant p53 oncogenic activity could provide an efficient
      strategy to treat human cancers. In this review we briefly summarize recent
      advances in the study of small molecules and compounds that subvert oncogenic
      activities of mutant p53 protein into wt-p53 tumor suppressor functions. We
      highlight inhibitors of signaling pathways aberrantly modulated by oncogenic
      mutant p53 proteins as promising therapeutic strategies. Finally, we consider the
      clinical applications of compounds targeting mutant p53 and the use of currently
      available drugs in the treatment of tumors expressing mutant p53 proteins.

PMID- 29448956
TI  - Immunomodulatory plasticity of mesenchymal stem cells: a potential key to
      successful solid organ transplantation.
AB  - Organ transplantation remains to be a treatment of choice for patients suffering
      from irreversible organ failure. Immunosuppressive (IS) drugs employed to
      maintain the allograft have shown excellent short-term graft survival, but, their
      long-term use could contribute to immunological and non-immunological risk
      factors, resulting in graft dysfunctionalities. Upcoming IS regimes have
      highlighted the use of cell-based therapies, which can eliminate the risk of drug
      borne toxicities while maintaining efficacy of the treatment. Mesenchymal stem
      cells (MSCs) have been considered as an invaluable cell type, owing to their
      unique immunomodulatory properties, which makes them desirable for application in
      transplant settings, where hyper-activation of the immune system is evident. The
      immunoregulatory potential of MSCs holds true for preclinical studies while
      achieving it in clinical studies continues to be a challenge. Understanding the
      biological factors responsible for subdued responses of MSCs in vivo would allow
      uninhibited use of this therapy for countless conditions. In this review, we
      summarize the variations in the preclinical and clinical studies utilizing MSCs,
      discuss the factors which might be responsible for variability in outcome and
      propose the advancements likely to occur in future for using this as a
      "boutique/personalised therapy" for patient care.

PMID- 29448958
TI  - Antigenic and functional profiles of a Lawsonia intracellularis protein that
      shows a flagellin-like trait and its immuno-stimulatory assessment.
AB  - The obligate intracellular Lawsonia intracellularis (LI), the etiological agent
      of proliferative enteropathy (PE), is an economically important disease in the
      swine industry. Due to extreme difficulty of in vitro culture of the pathogen,
      molecular characterization of protein components of LI that are targets of the
      immune system, is difficult; thus, the scientific evidence to drive the
      development of preventive measures is lacking. In this work, we investigated the
      antigenic and functional characteristics of a putative flagellar-associated
      protein, LI0570, using in silico computational approaches for epitope prediction
      and an in vitro protein-based molecular assay. The amino acid sequence of LI0570
      exhibited similarities to flagellar-associated proteins in four different
      bacterial strains. The presence of B cell linear confirmative epitopes of the
      protein predicted by a bioinformatics tool was validated by western blot analysis
      using anti-LI mouse hyperimmune serum, which implied that LI0570 induced
      production of antigen-specific antibodies in vivo. Further, TLR5-stimulating
      activity and IL-8 cytokine expression produced via downstream signaling were
      observed in HEK-BlueTM-hTLR5 cells stimulated with LI0570. This result indicates
      that the LI0570 protein can trigger an innate immune response followed by a T
      cell-related adaptive immune response in an infected host. Collectively, the data
      presented here support that the LI0570 protein which shows the antigenic
      potential could be a useful component of a recombinant vaccine against PE,
      providing progress toward an effective prevention strategy.

PMID- 29448957
TI  - Brain region-specific enhancement of remyelination and prevention of
      demyelination by the CSF1R kinase inhibitor BLZ945.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central
      nervous system (CNS). While multiple effective immunomodulatory therapies for MS
      exist today, they lack the scope of promoting CNS repair, in particular
      remyelination. Microglia play a pivotal role in regulating myelination processes,
      and the colony-stimulating factor 1 (CSF-1) pathway is a key regulator for
      microglia differentiation and survival. Here, we investigated the effects of the
      CSF-1 receptor kinase inhibitor, BLZ945, on central myelination processes in the
      5-week murine cuprizone model by non-invasive and longitudinal magnetic resonance
      imaging (MRI) and histology. Therapeutic 2-week BLZ945 treatment caused a brain
      region-specific enhancement of remyelination in the striatum/cortex, which was
      absent in the corpus callosum/external capsule. This beneficial effect correlated
      positively with microglia reduction, increased oligodendrocytes and astrogliosis.
      Prophylactic BLZ945 treatment prevented excessive demyelination in the corpus
      callosum by reducing microglia and increasing oligondendrocytes. In the external
      capsule oligodendrocytes were depleted but not microglia and a buildup of myelin
      debris and axonal damage was observed. A similar microglial dysfunction in the
      external capsule with an increase of myelin debris was obvious in triggering
      receptor expressed on myeloid cells 2 (TREM2) knock-out mice treated with
      cuprizone. Finally, therapeutic BLZ945 treatment did not change the disease
      course in experimental autoimmune encephalomyelitis mice, a peripherally driven
      neuroinflammation model. Taken together, our data suggest that a short-term
      therapeutic inhibition of the CSF-1 receptor pathway by BLZ945 in the murine
      cuprizone model enhances central remyelination by modulating neuroinflammation.
      Thus, microglia-modulating therapies could be considered clinically for promoting
      myelination in combination with standard-of-care treatments in MS patients.

PMID- 29448960
TI  - Double-negative (CD27-IgD-) B cells are expanded in NSCLC and inversely correlate
      with affinity-matured B cell populations.
AB  - BACKGROUND: The presence of B cells in early stage non-small cell lung cancer
      (NSCLC) is associated with longer survival, however, the role these cells play in
      the generation and maintenance of anti-tumor immunity is unclear. B cells
      differentiate into a variety of subsets with differing characteristics and
      functions. To date, there is limited information on the specific B cell subsets
      found within NSCLC. To better understand the composition of the B cell
      populations found in NSCLC we have begun characterizing B cells in lung tumors
      and have detected a population of B cells that are CD79A+CD27-IgD-. These CD27
      IgD- (double-negative) B cells have previously been characterized as
      unconventional memory B cells and have been detected in some autoimmune diseases
      and in the elderly population but have not been detected previously in tumor
      tissue. METHODS: A total of 15 fresh untreated NSCLC tumors and 15 matched
      adjacent lung control tissues were dissociated and analyzed by intracellular flow
      cytometry to detect the B cell-related markers CD79A, CD27 and IgD. All CD79A+ B
      cells subsets were classified as either naive (CD27-IgD+), affinity-matured
      (CD27+IgD-), early memory/germinal center cells (CD27+IgD+) or double-negative B
      cells (CD27-IgD-). Association of double-negative B cells with clinical data
      including gender, age, smoking status, tumor diagnosis and pathologic
      differentiation status were also examined using the logistic regression analysis
      for age and student's t-test for all other variables. Associations with other B
      cell subpopulations were examined using Spearman's rank correlation. RESULTS: We
      observed that double-negative B cells were frequently abundant in lung tumors
      compared to normal adjacent controls (13 out of 15 cases), and in some cases made
      up a substantial proportion of the total B cell compartment. The presence of
      double-negative cells was also found to be inversely related to the presence of
      affinity-matured B cells within the tumor, Spearman's coefficient of - 0.76.
      CONCLUSIONS: This study is the first to observe the presence of CD27-IgD- double
      negative B cells in human NSCLC and that this population is inversely correlated
      with traditional affinity-matured B cell populations.

PMID- 29448959
TI  - Impaired T cell-mediated hepatitis in peroxisome proliferator activated receptor
      alpha (PPARalpha)-deficient mice.
AB  - BACKGROUND: Peroxisome proliferator activated receptor alpha (PPARalpha), a
      regulator of enzymes involved in beta oxidation, has been reported to influence
      lymphocyte activation. The purpose of this study was to determine whether
      PPARalpha plays a role in T cell-mediated hepatitis induced by Concanavalin A
      (ConA). METHODS: Wild type (wt) or PPARalpha-deficient (PPARalpha-/-) mice were
      treated with ConA (15 mg/kg) by intravenous injection 0, 10 or 24 h prior to
      sacrifice and serum and tissue collection for analysis of tissue injury, cytokine
      response, T cell activation and characterization. RESULTS: Ten and 24 h following
      ConA administration, wt mice had significant liver injury as demonstrated by
      serum transaminase levels, inflammatory cell infiltrate, hepatocyte apoptosis,
      and expression of several cytokines including interleukin 4 (IL4) and interferon
      gamma (IFNgamma). In contrast, PPARalpha-/- mice were protected from ConA-induced
      liver injury with significant reductions in serum enzyme release, greatly reduced
      inflammatory cell infiltrate, hepatocellular apoptosis, and IFNgamma expression,
      despite having similar levels of hepatic T cell activation and IL4 expression.
      This resistance to liver injury was correlated with reduced numbers of hepatic
      natural killer T (NKT) cells and their in vivo responsiveness to alpha
      galactosylceramide. Interestingly, adoptive transfer of either wt or PPARalpha-/-
      splenocytes reconstituted ConA liver injury and cytokine production in lymphocyte
      deficient, severe combined immunodeficient mice implicating PPARalpha within the
      liver, possibly through support of IL15 expression and/or suppression of IL12
      production and not the lymphocyte as the key regulator of T cell activity and
      ConA-induced liver injury. CONCLUSION: Taken together, these data suggest that
      PPARalpha within the liver plays an important role in ConA-mediated liver injury
      through regulation of NKT cell recruitment and/or survival.

PMID- 29448961
TI  - Nuclear receptor agonist-driven modification of inflammation and amyloid
      pathology enhances and sustains cognitive improvements in a mouse model of
      Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is a highly prevalent neurodegenerative
      disorder characterized by pathological hallmarks of beta-amyloid plaque deposits,
      tau pathology, inflammation, and cognitive decline. Treatment remains a clinical
      obstacle due to lack of effective therapeutics. Agonists targeting nuclear
      receptors, such as bexarotene, reversed cognitive deficits regardless of
      treatment duration and age in murine models of AD. While bexarotene demonstrated
      marked efficacy in decreasing plaque levels following short-term treatment,
      prolonged treatment did not modulate plaque burden. This suggested that plaques
      might reform in mice treated chronically with bexarotene and that cessation of
      bexarotene treatment before plaques reform might alter amyloid pathology,
      inflammation, and cognition in AD mice. METHODS: We utilized one-year-old APP/PS1
      mice that were divided into two groups. We treated one group of mice for 2 weeks
      with bexarotene. The other group of mice was treated for 2 weeks with bexarotene
      followed by withdrawal of drug treatment for an additional 2 weeks. Cognition was
      evaluated using the novel-object recognition test either at the end of bexarotene
      treatment or the end of the withdrawal period. We then analyzed amyloid pathology
      and microgliosis at the conclusion of the study in both groups. RESULTS:
      Bexarotene treatment enhanced cognition in APP/PS1 mice similar to previous
      findings. Strikingly, we observed sustained cognitive improvements in mice in
      which bexarotene treatment was discontinued for 2 weeks. We observed a sustained
      reduction in microgliosis and plaque burden following drug withdrawal exclusively
      in the hippocampus. CONCLUSIONS: Our findings demonstrate that bexarotene
      selectively modifies aspects of neuroinflammation in a region-specific manner to
      reverse hippocampal-dependent cognitive deficits in AD mice and may provide
      insight to inform future studies with nuclear receptor agonists.

PMID- 29448963
TI  - Academic medical centers as innovation ecosystems to address population -omics
      challenges in precision medicine.
AB  - While the promise of the Human Genome Project provided significant insights into
      the structure of the human genome, the complexities of disease at the individual
      level have made it difficult to utilize -omic information in clinical decision
      making. Some of the existing constraints have been minimized by technological
      advancements that have reduced the cost of sequencing to a rate far in excess of
      Moore's Law (a halving in cost per unit output every 18 months). The reduction in
      sequencing costs has made it economically feasible to create large data commons
      capturing the diversity of disease across populations. Until recently, these data
      have primarily been consumed in clinical research, but now increasingly being
      considered in clinical decision- making. Such advances are disrupting common
      diagnostic business models around which academic medical centers (AMCs) and
      molecular diagnostic companies have collaborated over the last decade.
      Proprietary biomarkers and patents on proprietary diagnostic content are no
      longer driving biomarker collaborations between industry and AMCs. Increasingly
      the scope of the data commons and biorepositories that AMCs can assemble through
      a nexus of academic and pharma collaborations is driving a virtuous cycle of
      precision medicine capabilities that make an AMC relevant and highly competitive.
      A rebalancing of proprietary strategies and open innovation strategies is
      warranted to enable institutional precision medicine asset portfolios. The scope
      of the AMC's clinical trial and research collaboration portfolios with industry
      are increasingly dependent on the currency of data, and less on patents.
      Intrapeneurial support of internal service offerings, clinical trials and
      clinical laboratory services for example, will be important new points of
      emphasis at the academic-industry interface. Streamlining these new models of
      industry collaboration for AMCs are a new area for technology transfer offices to
      offer partnerships and to add value beyond the traditional intellectual property
      offering.

PMID- 29448964
TI  - Utility of rituximab treatment for exophthalmos, myxedema, and osteoarthropathy
      syndrome resistant to corticosteroids due to Graves' disease: a case report.
AB  - BACKGROUND: Exophthalmos, myxedema, and osteoarthropathy syndrome is a very rare
      condition that is associated with Graves' disease. The presence of dermopathy and
      the involvement of joint/bone tissues indicate that it seems to be related with
      the severity of the autoimmune process. Owing to its low incidence, there is a
      lack of information regarding its treatment and clinical follow-up. Some cases
      improved after use of high doses of steroids; however, some patients do not
      respond to this treatment. Recently, the effectiveness of rituximab for treatment
      of Graves' ophthalmopathy resistant to corticosteroids has been demonstrated.
      However, it has never been used for the treatment of exophthalmos, myxedema, and
      osteoarthropathy syndrome (particularly for the treatment of osteoarticular
      manifestations). CASE PRESENTATION: We present the case of a 54-year-old Mexican
      woman previously treated for Graves' disease who developed post-iodine
      hypothyroidism and exophthalmos, myxedema, and osteoarthropathy that did not
      improve after high doses of steroids (intravenous and oral). Her exophthalmos,
      myxedema, and osteoarthropathy syndrome symptoms improved as early as 6 months
      after treatment with rituximab. CONCLUSION: Exophthalmos, myxedema, and
      osteoarthropathy syndrome is a non-classical presentation of Graves' disease,
      whose clinical manifestations could improve after treatment with rituximab,
      particularly in those patients with lack of response to high doses of
      corticosteroids.

PMID- 29448962
TI  - Non-viral gene delivery systems for tissue repair and regeneration.
AB  - Critical tissue defects frequently result from trauma, burns, chronic wounds
      and/or surgery. The ideal treatment for such tissue loss is autografting, but
      donor sites are often limited. Tissue engineering (TE) is an inspiring
      alternative for tissue repair and regeneration (TRR). One of the current state-of
      the-art methods for TRR is gene therapy. Non-viral gene delivery systems (nVGDS)
      have great potential for TE and have several advantages over viral delivery
      including lower immunogenicity and toxicity, better cell specificity, better
      modifiability, and higher productivity. However, there is no ideal nVGDS for TRR,
      hence, there is widespread research to improve their properties. This review
      introduces the basic principles and key aspects of commonly-used nVGDSs. We focus
      on recent advances in their applications, current challenges, and future
      directions.

PMID- 29448965
TI  - Temporo-spatial dynamics and behavioural patterns of 2012 cholera epidemic in the
      African mega-city of Conakry, Guinea.
AB  - BACKGROUND: Cholera is endemic in Guinea, having suffered consecutive outbreaks
      from 2004 to 2008 followed by a lull until the 2012 epidemic. Here we describe
      the temporal-spatial and behavioural characteristics of cholera cases in Conakry
      during a three-year period, including the large-scale 2012 epidemic. METHODS: We
      used the national and African Cholera Surveillance Network (Africhol)
      surveillance data collected from every cholera treatment centre in Conakry city
      from August 2011 to December 2013. The prevalence of suspect and confirmed
      cholera cases, the case fatality ratio (CFR), and the factors associated with
      suspected cholera were described according to three periods: pre-epidemic (A),
      epidemic 2012 (B) and post epidemic (C). Weekly attack rates and temporal-spatial
      clustering were calculated at municipality level for period B. Cholera was
      confirmed by culture at the cholera national reference laboratory. RESULTS: A
      total of 4559 suspect cases were reported: 66, 4437, and 66 suspect cases in
      periods A, B and C, respectively. Among the 204 suspect cases with culture
      results available, 6%, 60%, and 70% were confirmed in periods A, B, and C,
      respectively. With 0.3%, the CFR was significantly lower in period B than in
      periods A (7.6%) and C (7.1%). The overall attack rate was 0.28% in period B,
      ranging from 0.17% to 0.31% across municipalities. Concomitantly, a cluster of
      cases was identified in two districts in the northern part of Conakry. At 14%,
      rice water stools were less frequent in period A than in period B and C (78% and
      84%). Dehydration (31% vs 94% and 89%) and coma (0.4% vs 3.1% and 2.9%) were
      lower during period B than in periods A and C. The treatment of drinking water
      was less frequent in period A, while there were more reports of recent travel in
      period C. CONCLUSIONS: The epidemic dynamic and the sociological description of
      suspect cases before, during, and after the large-scale epidemic revealed that
      the Vibrio cholerae was already present before the epidemic. However, it appeared
      that infected individuals reacted differently in terms of disease severity as
      well as their access to treated water and travel habits. Such an in-depth
      description of cholera epidemics should be systematically carried out in cholera
      endemic settings in order to prioritize higher risk areas, identify transmission
      factors, and optimize preventive interventions.

PMID- 29448966
TI  - Exosomes taken up by neurons hijack the endosomal pathway to spread to
      interconnected neurons.
AB  - In Alzheimer disease and related disorders, the microtubule-associated protein
      tau aggregates and forms cytoplasmic lesions that impair neuronal physiology at
      many levels. In addition to affecting the host neuron, tau aggregates also spread
      to neighboring, recipient cells where the misfolded tau aggregates, in a manner
      similar to prions, actively corrupt the proper folding of soluble tau, and
      thereby impair cellular functions. One vehicle for the transmission of tau
      aggregates are secretory nanovesicles known as exosomes. Here, we established a
      simple model of a neuronal circuit using a microfluidics culture system in which
      hippocampal neurons A and B were seeded into chambers 1 and 2, respectively,
      extending axons via microgrooves in both directions and thereby interconnecting.
      This system served to establish two models to track exosome spreading. In the
      first model, we labeled the exosomal membrane by coupling tetraspanin CD9 with
      either a green or red fluorescent tag. This allowed us to reveal that
      interconnected neurons exchange exosomes only when their axons extend in close
      proximity. In the second model, we added exosomes isolated from the brains of tau
      transgenic rTg4510 mice (i.e. exogenous, neuron A-derived) to neurons in chamber
      1 (neuron B) interconnected with neuron C in chamber 2. This allowed us to
      demonstrate that a substantial fraction of the exogenous exosomes were
      internalized by neuron B and passed then on to neuron C. This transportation from
      neuron B to C was achieved by a mechanism that is consistent with the hijacking
      of secretory endosomes by the exogenous exosomes, as revealed by confocal, super
      resolution and electron microscopy. Together, these findings suggest that fusion
      events involving the endogenous endosomal secretory machinery increase the
      pathogenic potential and the radius of action of pathogenic cargoes carried by
      exogenous exosomes.

PMID- 29448967
TI  - Facial nerve stimulation in normal pigs and healthy human volunteers:
      transitional development of a medical device for the emergency treatment of
      ischemic stroke.
AB  - BACKGROUND: Magnetic stimulation of the facial nerve has been tested in
      preclinical studies as a new, non-invasive emergency treatment of ischemic stroke
      that acts by increasing cerebral blood flow (CBF). The objective of the studies
      reported herein was to identify minimal stimulation parameters that increase CBF
      in large animals and then test those stimulation parameters in healthy volunteers
      for safety, tolerability, and effectiveness at increasing CBF. This translational
      research is necessary preparation for clinical studies in ischemic stroke
      patients. METHODS: Initial experiments in anesthetized Yorkshire pigs were
      undertaken in order to identify the lowest stimulus power and duration that
      increase CBF. A full 3 * 3 factorial design was used to evaluate magnetic
      stimulation of the facial nerve at various stimulation powers (1.3, 1.6, and 1.9
      Tesla field strength at coil surface) and for various durations (2, 3.5, and 5
      min). CBF was measured with contrast MRI perfusion imaging and the internal
      carotid arteries were assessed with MR angiography. Magnetic facial nerve
      stimulation with parameters identified in the pig study was then applied to 35
      healthy volunteers. Safety was assessed with adverse event reports and by medical
      examination. Tolerability was defined as each volunteer's ability to withstand at
      least 2 min of stimulation. Volunteers could determine the maximum power of
      stimulation they received during a ramp-up period. RESULTS: In pigs, unilateral
      facial nerve stimulation increased CBF by as much as 77% over pre-stimulation
      baseline when administered across a range of 1.3-1.9 Tesla power and for 2- to 5
      min duration. No clear dose-response relationship could be observed across this
      range, but lower powers and durations than these were markedly less effective.
      The effect of a single stimulation lasted 90 min. A second stimulation delivered
      100 min after the first stimulation sustained the increased CBF without evidence
      of tachyphylaxis. In human, bilateral facial nerve stimulation caused only non
      serious adverse events that were limited to the 2-min stimulation period.
      Tolerability was greatly improved by gentle encouragement from the study staff,
      which enabled most volunteers to tolerate 1.6-1.8 Tesla of stimulation power. CBF
      measures taken approximately 10 min after stimulation demonstrated on average a
      32 +/- 6% increase in CBF, with >= 25% increases in CBF occurring in 10 of the 31
      volunteers who had adequate CBF measurements. CONCLUSIONS: The minimal effective
      stimulation parameters defined by increased CBF, as identified in the pig study,
      translated into safe, tolerable, and effective stimulation of healthy volunteers.
      These results support the future development and evaluation of non-invasive
      facial nerve stimulation for the emergency treatment of ischemic stroke. Trial
      Registration retrospectively registered with clinicaltrials.gov NRV_P1_01_15 on
      June 6, 2017.

PMID- 29448968
TI  - Corporate practices and health: a framework and mechanisms.
AB  - BACKGROUND: The Global Burden of Disease estimates that approximately a third of
      deaths worldwide are attributable to behavioural risk factors that, at their
      core, have the consumption of unhealthful products and exposures produced by
      profit driven commercial entities. We use Steven Lukes' three-dimensional view of
      power to guide the study of the practices deployed by commercial interests to
      foster the consumption of these commodities. Additionally, we propose a framework
      to systematically study corporations and other commercial interests as a distal,
      structural, societal factor that causes disease and injury. Our framework offers
      a systematic approach to mapping corporate activity, allowing us to anticipate
      and prevent actions that may have a deleterious effect on population health.
      CONCLUSION: Our framework may be used by, and can have utility for, public health
      practitioners, researchers, students, activists and other members of civil
      society, policy makers and public servants in charge of policy implementation. It
      can also be useful to corporations who are interested in identifying key actions
      they can take towards improving population health.

PMID- 29448970
TI  - Dementia clinical trial implications of mild behavioral impairment.
AB  - The World Alzheimer Report 2016 estimated that 47 million people are living with
      dementia worldwide (Alzheimer's Disease International, 2016). In the inaugural
      World Health Organization Ministerial Conference on Global Action against
      Dementia, six of the top ten research priorities were focused on prevention,
      identification, and reduction of dementia risk, and on delivery and quality of
      care for people with dementia and their carers (Shah et al., 2016). While the
      Lancet Neurology Commission has suggested that even minor advances to delay
      progression or ameliorate symptoms might have substantial financial and societal
      benefits (Winblad et al., 2016), advances have been slow.

PMID- 29448969
TI  - Prevalence of erectile dysfunction and associated factors among diabetic men
      attending the diabetic clinic at Felege Hiwot Referral Hospital, Bahir Dar, North
      West Ethiopia, 2016.
AB  - OBJECTIVE: Even though several scholars have conducted study in different part of
      the world on erectile dysfunction in patients diagnosed with diabetes mellitus,
      it's magnitude vary among their finding with the range between 20 and 90%. This
      study aimed at assessing the prevalence of erectile dysfunction and associated
      factors among diabetic clients. RESULTS: A cross sectional study was conducted
      from January 2016 to March, 2016. Systematic random sampling technique was used.
      Data were collected using a structured questionnaire and level of erectile
      dysfunction was measured using the international index of erectile function. A
      total of 422 diabetic patients were participated with 100% response rate. The
      proportion of erectile dysfunction was 85.5% and it was significantly associated
      with higher age (AOR: 6.46, 95% CI 2.55-16.44) and Diabetic complication (AOR:
      3.97, 95% CI 1.06-17.36). Therefore, screening for ED in diabetic patients,
      particularly for those who are in advanced age and living with DM for more than
      10 years is needed for it's early detection, prevention and management.

PMID- 29448971
TI  - Special Issue on mild behavioral impairment and non-cognitive prodromes to
      dementia.
AB  - This Special Issue provides a systematic examination of the neuropsychiatric
      symptoms (NPS) and non-cognitive prodromes of dementia, with an eye toward
      validating the construct of mild behavioral impairment (MBI).

PMID- 29448972
TI  - Bullying and sexual harassment of junior doctors in New South Wales, Australia:
      rate and reporting outcomes.
AB  - Objective The aim of this study was to describe rates of exposure to bullying and
      sexual harassment in junior doctors in first- or second-year prevocational
      medical training (PGY1 or PGY2 respectively) positions in New South Wales (NSW)
      and the Australian Capital Territory (ACT), and to explore the types of actions
      taken in response.Methods A cross-sectional survey of junior doctors in PGY1 or
      PGY2 positions was undertaken in 2015 and 2016 (n=374 and 440 respectively).
      Thematic analysis was undertaken on free-text responses to describe the reporting
      process and outcomes in more depth.Results The estimated response rate was 17
      20%. Results from both surveys followed almost identical trends. Most respondents
      in 2015 and 2016 reported being bullied (n=203 (54.3%) and 253 (57.5%)
      respectively), 16-19% reported sexual harassment (n=58 and 82 respectively) and
      29% of females reported sexual harassment. Qualitative analysis elucidated
      reasons for not taking action in response to bullying and harassment, including
      workplace normalisation of these behaviours, fear of reprisal and lack of
      knowledge or confidence in the reporting process. For respondents who did take
      action, most reported ineffective or personally harmful outcomes when reporting
      to senior colleagues, including being dismissed or blamed, and an intention not
      to trust the process in the future.Conclusions The findings suggest that
      interventions targeted at the level of junior doctors to improve the culture of
      bullying and harassment in medicine are unlikely to be helpful. Different
      approaches that address the problem in a more systemic way are needed, as is
      further research about the effectiveness of such interventions.What is known
      about the topic? Bullying and sexual harassment are common workplace experiences
      in the medical profession.What does this paper add? Over half the junior doctors
      in the present study experienced bullying and nearly one-fifth experienced sexual
      harassment. Junior doctors are reluctant to speak out, not only for fear of
      reprisal, but also because they do not believe it is worth doing so.What are the
      implications for practitioners? The data confirm a systemic problem of bullying
      in NSW. Primarily focusing on interventions with junior doctors (e.g. resilience
      training) is unlikely to solve the problem. Different and multipronged approaches
      (e.g. raising awareness in senior colleagues and training bystanders to
      intervene) should be tried and studied.

PMID- 29448973
TI  - cAMP response element-binding protein 1 controls porcine ovarian cell
      proliferation, apoptosis, and FSH and insulin-like growth factor 1 response.
AB  - The aim of the present study was to examine the role of cAMP response element
      binding protein (CREB) and its phosphorylation in the regulation of ovarian cell
      proliferation and apoptosis, and of the response of proliferation and apoptosis
      to the upstream hormonal stimulators FSH and insulin-like growth factor (IGF) 1.
      In the first series of experiments, porcine ovarian granulosa cells, transfected
      or not with a gene construct encoding wild-type CREB1 (CREB1WT), were cultured
      with and without FSH (0, 1, 10 or 100ngmL-1). In the second series of
      experiments, these cells were transfected or not with CREB1WT or non
      phosphorylatable mutant CREB1 (CREB1M1) and cultured with and without FSH (0, 1,
      10 or 100ngmL-1) or IGF1 (0, 1, 10 and 100ngmL-1). Levels of total and
      phosphorylated (p-) CREB1, proliferating cell nuclear antigen (PCNA), a marker of
      proliferation, and BAX, a marker of apoptosis, were evaluated by western
      immunoblotting and immunocytochemical analysis. Transfection of cells with
      CREB1WT promoted accumulation of total CREB1 within cells, but p-CREB1 was not
      detected in any cell group. Both CREB1WT and CREB1M1 reduced cell proliferation
      and apoptosis. Addition of 10 and 100ngmL-1 FSH to non-transfected cells promoted
      CREB1 accumulation and apoptosis, whereas cell proliferation was promoted by all
      concentrations of FSH tested. FSH activity was not modified in cells transfected
      with either CREB1WT or CREB1M1. IGF1 at 100ngmL-1 promoted cell proliferation,
      whereas all concentrations of IGF1 tested reduced apoptosis. Transfection with
      either CREB1WT or CREB1M1 did not modify the effects of either FSH or IGF1,
      although CREB1M1 reversed the effect of IGF1 on apoptosis from inhibitory to
      stimulatory. These observations suggest that CREB1 is involved in the
      downregulation of porcine ovarian cell proliferation and apoptosis. The absence
      of visible CREB1 phosphorylation and the similarity between the effects of
      CREB1WT and CREB1M1 transfection indicate that phosphorylation is not necessary
      for CREB1 action on these processes. Furthermore, the observations suggest that
      FSH promotes both ovarian cell proliferation and apoptosis, whereas IGF1 has
      proliferation-promoting and antiapoptotic properties. The effect of FSH on CREB1
      accumulation and the ability of CREB1M1 to reverse the effects of IGF1 on
      apoptosis indicate that CREB1 is a mediator of hormonal activity, but the
      inability of either CREB1WT or CREBM1transfection to modify the primary effects
      of FSH and IGF1 suggest that CREB1 and its phosphorylation do not mediate the
      action of these hormones on ovarian cell proliferation and apoptosis.

PMID- 29448974
TI  - Phyto-oestrogens affect fertilisation and embryo development in vitro in sheep.
AB  - Phyto-oestrogens such as isoflavones are natural compounds that can profoundly
      affect reproductive function. In the present study, we tested whether including
      isoflavone compounds (genistein, biochanin A, formononetin) in the maturation
      medium would affect the outcomes for ovine oocytes in vitro. Each isoflavone
      compound was evaluated at five concentrations (0, 2.5, 5, 10, 25ugmL-1) and the
      entire protocol was repeated four times. Cumulus-oocyte complexes were randomly
      allocated to the treatments, then fertilised and cultured in vitro. Compared with
      control (0ugmL-1), the lower concentrations of isoflavone (2.5, 5 and 10ugmL-1)
      had no detectable effect on the rates of cleavage or embryo development, or on
      embryo total cell counts (TCC). However, the highest concentration (25ugmL-1) of
      all three isoflavones exerted a variety of effects (P<0.05): genistein decreased
      cleavage rate, blastocyst rate and blastocyst efficiency (blastocysts produced
      per 100 oocytes); biochanin A decreased cleavage rate and blastocyst efficiency;
      and formononetin decreased blastocyst rate and blastocyst efficiency. Biochanin A
      (25ugmL-1) reduced embryo TCC specifically at the hatched blastocyst stage
      (P<0.05). We conclude that the presence of isoflavones at 25ugmL-1 during IVM
      decreases the cleavage rate and inhibits blastocyst hatching.

PMID- 29448975
TI  - Analysis of patients with hypomagnesemia using the Japanese Adverse Drug Event
      Report database (JADER).
AB  - PURPOSE: In order to clarify the occurrence of hypomagnesemia in Japan, we
      conducted a database search and analysis using the Japanese Adverse Drug Event
      Report database (JADER). METHODS: Among the cases recorded in JADER between April
      2004 and December 2015, we targeted "hypomagnesemia" and analyzed the patients'
      backgrounds, drug involvement, other adverse events reported with hypomagnesemia,
      the time of hypomagnesemia onset, outcomes, and year when reported. For drugs
      with three or more reports, the signal index was calculated using the Reporting
      Odds Ratio (ROR) method. In addition, the association between hypomagnesemia
      onset and other adverse events was investigated using association analysis.
      RESULTS: The total number of reported hypomagnesemia cases was 201. Males
      accounted for 62.7%, and patients in their sixties formed a large peak. Three or
      more cases were reported for 23 causative drugs, among which anti-EGFR antibody,
      calcineurin inhibitor, platinum antitumor agent and proton pump inhibitor
      accounted for the majority. ROR analysis detected signals for 18 drugs, and an
      association was found between hypomagnesemia and other electrolyte abnormalities
      for those drugs. The median time until onset of hypomagnesemia was classified
      into three patterns: around 10 days, around 30 days, and longer. Analysis of the
      report year revealed an increasing tendency in recent years, although
      increases/decreases were evident depending on fiscal years. CONCLUSION: Our
      survey was able to reveal the factors associated with the occurrence of
      hypomagnesemia.

PMID- 29448976
TI  - In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase
      Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide
      Synthase Activation.
AB  - PURPOSE: In endothelial cells, investigate if the soluble guanylate cyclase (sGC)
      activation or stimulation is able to potentiate the relaxation in vessels.
      METHODS: Aortic and coronary rings with and without endothelium were placed in a
      myograph and cumulative concentration-effect curves for DETA-NO or ataciguat were
      performed. Nitric oxide (NO) were measured by fluorescence or by selective
      electrode in human umbilical endothelial cells (HUVECs) in response to some
      treatments, including ataciguat, 8-Br-cGMP and A23187. RESULTS: The presence of
      the endothelium potentiated the relaxation induced by DETA-NO in aortic and
      coronary rings. In addition, in aortic rings the endothelium potentiated the
      relaxation induced by ataciguat. In the presence of nitric oxide synthase (NOS)
      inhibitor, the endothelium effect was abolished to DETA-NO or ataciguat, in both
      vessels. Ataciguat, 8-Br-cGMP and A23187 were able to induce NO production in
      HUVECs cells. In the presence of NOS inhibitor, the NO production induced by
      ataciguat and 8-Br-cGMP was abolished. CONCLUSIONS: Our results suggest that in
      aortic and coronary rings the endothelium potentiates the relaxation induced by
      activation or stimulation of sGC through a mechanism dependent of NOS activation.
      This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For
      Readers") may comment by clicking on ABSTRACT on the issue's contents page.

PMID- 29448977
TI  - Corrigendum to 'Effects of RG7652, a Monoclonal Antibody Against PCSK9, on Low
      Density Lipoprotein Cholesterol (LDL-C), LDL-C Subfractions, and Inflammatory
      Biomarkers in Patients at High Risk of or with Established Coronary Heart Disease
      (From the Phase 2 EQUATOR Study)' The American Journal of Cardiology 119 (2017)
      1576-1583.

PMID- 29448978
TI  - Effect of Gender on Unplanned Readmissions After Percutaneous Coronary
      Intervention (from the Nationwide Readmissions Database).
AB  - Women who undergo percutaneous coronary intervention (PCI) are at higher risk of
      adverse outcomes compared with men, but it is unknown whether gender affects
      early unplanned rehospitalization. We analyzed 832,753 patients who underwent PCI
      from 2013 to 2014 in the Nationwide Readmissions Database. We compared gender
      differences in incidences, predictors, causes, and cost of unplanned 30-day
      readmissions and examined the effect of co-morbidity. A total of 832,753 men and
      women who survived the index PCI and were not admitted for a planned readmission
      were included in the analysis. Overall, 9.4% of patients had an unplanned
      readmission within 30 days. Thirty-day readmission rates were higher in women
      compared with men (11.5% vs 8.4%, p <0.001) even after multivariate adjustment
      (odds ratio 1.19, 95% confidence interval 1.16 to 1.22, p <0.001), although women
      had significantly lower costs associated with the readmission ($11,927 vs
      $12,758, p <0.001). The cause of readmission for women and men were similar and
      the majority of the readmissions were due to noncardiac causes (58% vs 55%), the
      most common of which were nonspecific chest pain, gastrointestinal disease, and
      infections. In contrast, for cardiac readmissions, women are more likely to be
      readmitted for heart failure (29.64% vs 22.34%), whereas men are more likely to
      be readmitted for coronary artery disease, including angina (33.47% vs 28.54%).
      In conclusion, gender disparities exist in rates of unplanned rehospitalization
      after PCI, where more than 1 in 10 women who undergo PCI are readmitted within 30
      days. Gender differences were not observed for causes of noncardiac readmissions,
      whereas important differences were observed for cardiovascular causes.

PMID- 29448979
TI  - CD103+CD8+ T lymphocytes in non-small cell lung cancer are phenotypically and
      functionally primed to respond to PD-1 blockade.
AB  - CD103+CD8+ tumor infiltrating lymphocytes (TILs) have been linked to prolonged
      survival in various types of cancer including non-small cell lung cancer (NSCLC).
      However, the factors associated with the retention of CD103+CD8+ TILs in lung
      cancer tissues remain largely unknown. Additionally, the contribution of
      CD103+CD8+ TILs to effective PD-1 based immunotherapy has not been fully
      elucidated. In this study, we identified that the expression levels of E-cadherin
      and TGF-beta were significantly correlated with the distribution and the density
      of CD103+ TILs in lung cancer tumor tissues. Unexpectedly, we observed that
      CD103+CD8+ TILs that expressed higher levels of PD-1 co-express Ki-67. Moreover,
      CD103+CD8+ TILs expressed an increased level of T-bet compared to their
      counterparts, indicating these cells may be better armed for immunotherapy.
      Lastly, PD-1 pathway blockade led to a significantly increased production of IFN
      gamma by CD103+CD8+ TILs, suggesting CD103+CD8+ TILs could serve as a predictive
      biomarker for PD-1 based immunotherapy.

PMID- 29448980
TI  - Determination of the optimal cut-off value of serum uric acid concentration in
      patients with acute coronary syndrome.

PMID- 29448981
TI  - Treatment and prevention of invasive pneumococcal disease.
AB  - Invasive pneumococcal disease is a severe infection that mainly affects patients
      with associated comorbidity. The paediatric conjugate vaccination has resulted in
      a change in the adult vaccination strategy. The antibiotic resistance of
      pneumococcus is not currently a severe problem. Nevertheless, the World Health
      Organisation has included pneumococcus among the bacteria whose treatment
      requires the introduction of new drugs, such as ceftaroline and ceftobiprole.
      Although the scientific evidence is still limited, the combination of beta
      lactams and macrolides is recommended as empiric therapy for bacteraemic
      pneumococcal pneumonia.

PMID- 29448982
TI  - Stochastic Gating as a Novel Mechanism for Channel Selectivity.
AB  - An ideal channel, responsible for metabolite fluxes in and out of the cells and
      cellular compartments, is supposed to be selective for a particular set of
      molecules only. However, such a channel has to be wide enough to accommodate
      relatively large metabolites, and, therefore, it allows passage of smaller
      solutes, for example, sodium, potassium, and chloride ions, thus compromising
      membrane's barrier function. Here we show that stochastic gating is able to
      provide a mechanism for the selectivity of wide channels in favor of large
      metabolites. Specifically, applying our recent theory of the stochastic gating
      effect on channel-facilitated transport, we demonstrate that under certain
      conditions gating hinders translocation of fast-diffusing small solutes to a
      significantly higher degree than that of large solutes that diffuse much slower.
      We hypothesize that this can be used by Nature to minimize the shunting effect of
      wide channels with respect to small solutes.

PMID- 29448983
TI  - Ruptured Anastomotic Pseudoaneurysm of the Common Femoral Artery After Wrongful
      Diagnosis of Inguinal Hernia.

PMID- 29448984
TI  - Transanal endoscopic microsurgery treatment of twice recurred tail-gut.

PMID- 29448985
TI  - Complex Perianal Fistula.

PMID- 29448986
TI  - Continuous hemoglobin monitoring in pediatric trauma patients with solid organ
      injury.
AB  - BACKGROUND/PURPOSE: Hemoglobin monitoring is required in pediatric trauma
      patients with solid organ injury. We hypothesized that noninvasive hemodynamic
      monitoring (NIHM) represents an effective, safe alternative to laboratory
      hemoglobin (LabHb) monitoring in clinically stable patients. METHODS: A
      retrospective cohort study was conducted regarding pediatric trauma patients (<18
      years old) with blunt solid organ injury over six consecutive months. Continuous
      NIHM was initiated at the time of admission, and LabHb measurements were obtained
      per institutional guidelines. Measurements were correlated within two hours of
      assessment and patient outcomes were analyzed. RESULTS: Twenty-one patients met
      inclusion criteria and had evaluable data. Blunt trauma was the exclusive
      mechanism of injury, and mean injury severity score was 16.6 for the cohort.
      Bland Altman analysis showed an average deviation of 0.80 g/dL between NIHM and
      LabHb values for all data pairs. Measurement trends were highly correlated in
      patients with stable hemoglobin levels and those requiring blood transfusion.
      CONCLUSIONS: NIHM demonstrated clinically acceptable accuracy when following
      hemoglobin trends in the defined pediatric trauma patient population. Slight
      variances between NIHM and LabHb values were occasionally noted, but did not
      affect clinical management. Continuous NIHM represents a potentially valuable
      adjunct to traditional laboratory hemoglobin monitoring. LEVEL OF EVIDENCE
      RATING: IV.

PMID- 29448987
TI  - The refeeding syndrome. Importance of phosphorus.
AB  - Refeeding syndrome (RS) is a complex disease that occurs when nutritional support
      is initiated after a period of starvation. The hallmark feature is the
      hypophosphataemia, however other biochemical abnormalities like hypokalaemia,
      hypomagnesaemia, thiamine deficiency and disorder of sodium and fluid balance are
      common. The incidence of RS is unknown as no universally accepted definition
      exists, but it is frequently underdiagnosed. RS is a potentially fatal, but
      preventable, disorder. The identification of patients at risk is crucial to
      improve their management. If RS is diagnosed, there is one guideline (NICE 2006)
      in place to help its treatment (but it is based on low quality of evidence). The
      aims of this review are: highlight the importance of this problem in malnourished
      patients, discuss the pathophysiology and clinical characteristics, with a final
      series of recommendations to reduce the risk of the syndrome and facilitate the
      treatment.

PMID- 29448988
TI  - Public awareness and knowledge of stuttering in Japan.
AB  - PURPOSE: To determine laypeople's knowledge and awareness of stuttering in Japan.
      METHODS: A total of 303 respondents, recruited by street sampling, completed a
      questionnaire assessing the prevalence, onset, gender distribution, occurrence in
      different races, cause, treatment, association with intelligence, and
      hereditariness of stuttering. The questionnaire used was a Japanese version of
      that devised by Van Borsel, Verniers, and Bouvry (1999) for use in Belgium.
      RESULTS: Although around half of the respondents had heard or met a stutterer,
      they tended to misunderstand the stuttering; e.g., respondents estimated the
      prevalence of stuttering as high. Knowledge also differed according to age,
      gender, and education level. Specifically, older individuals, females, and
      individuals with higher levels of education tended to have greater knowledge of
      stuttering. In comparing the results of the present study with similar studies
      conducted in Belgium, China, and Brazil, we observed several similarities and
      differences. DISCUSSION: Although most respondents were to some extent familiar
      with stuttering, their overall knowledge of the condition was limited. Certain
      factors could be involved in having knowledge of stuttering, such as one's life
      experience, cultural background, and social attitudes toward stuttering. The
      findings suggest the need for growing knowledge and awareness of stuttering.

PMID- 29448989
TI  - Redefining "bowel regimen": Pharmacologic strategies and nutritional
      considerations in the management of small bowel fistulas.
AB  - Enterocutaneous fistulae (ECF) and enteroatmospheric fistulae (EAF) are difficult
      complications that primarily arise after abdominal surgical procedures.
      Development of an ECF or EAF carries significant mortality and morbidity.
      Effective management of patients with these disease states requires a
      multidisciplinary approach, which includes surgical, pharmacotherapeutic, and
      nutritional interventions. This review focuses on the medical and nutritional
      management of ECF/EAF, providing background on drug agents and nutritional
      strategies that may be helpful in reducing effluent volume, optimizing fistula
      healing, and maintaining nutritional health.

PMID- 29448990
TI  - Open abdomen in liver transplantation.
AB  - INTRODUCTION: Damage control laparotomy with vacuum assisted closure (VAC) is
      used for selective cases in trauma. In liver transplantation, VAC has also been
      applied for management of intra-operative hemorrhage. The primary objective was
      to evaluate peri-operative blood loss and blood product utilization in VAC
      compared to primary abdominal closure (PAC) at the index transplant operation.
      METHODS: Retrospective review of all adults undergoing deceased donor liver
      transplantation (2007-2011) at a single center tertiary care institution.
      RESULTS: 201 deceased donor liver transplantations were performed, with 167 PAC
      and 34 VAC cases. Intra-operative blood loss (4.4L vs 10.7L), cell saver return
      (1399 ml vs 3998 ml), FFP (7.6U vs 15.9U) and PLT requirements (8.5U vs 18.3U),
      were all significantly elevated in VAC compared to PAC. VAC patients had
      significantly increased RBC, FFP, PLT, and total volume requirements during
      initial ICU admission. 30 PAC cases required on demand laparotomy and most
      commonly for post-operative bleeding. CONCLUSION: In liver transplantation,
      application of VAC secondary to massive intra-operative exsanguination was safely
      utilized. Further evaluation is required to identify long-term morbidity and
      mortality.

PMID- 29448992
TI  - Medulloblastoma: A turning point from fundamental advances to improved survival
      and decreased sequelae.

PMID- 29448991
TI  - Paediatric pelvic fractures: A review of 2 cohorts over 22 years.
AB  - AIMS: The aim of this retrospective review was to identify all children that
      presented to our institution with a pelvic or acetabular fracture and to compare
      these children to a previous cohort of paediatric pelvic fractures that we have
      reported. PATIENTS: 53 children under the age of 16 were identified over a ten
      year period. METHODS: We reviewed our trauma database, hospital records and
      radiological imaging to determine the age, gender, fracture pattern, associated
      injuries and management of the pelvic fracture. RESULTS: There were 32 boys and
      21 girls. Mean age of the boys was 8.8 years and the girls 10.7 years. In seven
      children the pelvic fracture was an isolated injury and in the remaining 46
      children, there were 113 additional injuries. 56% of the additional injuries was
      either a fracture/dislocation (37%) or a head injury (19%). Compared to our first
      cohort, we had a larger number of children in the second cohort. Age, sex
      distribution, mechanism of injury was similar in the two groups. In this current
      cohort, use of CT scan imaging was more frequent, there were more unstable pelvic
      fracture patterns identified, ISS scores were higher and mortality was lower.
      CONCLUSION: We have seen more children with more severe injuries, higher ISS
      scores but a lower mortality rate.

PMID- 29448993
TI  - Adjacent level spondylodiscitis in a patient with thoracic spondylodiscitis: A
      case report and review of the literature.
AB  - INTRODUCTION: Adjacent level spondylodiscitis (ALS) after primary surgery for
      thoracic spondylodiscitis is a very rare condition. CASE REPORT: We report the
      case of a 76-year-old man with this pathology. A first posterior minimally
      invasive approach combined with anterior approach to the thoracic spine was
      safely performed for thoracic spondylodiscitis. More than a year later,
      exploration of recurrent symptoms with 18FDG PET scan helped to diagnose ALS.
      Further surgery was performed. At 3-year follow-up examination showed no
      recurrence of the infection. DISCUSSION: ALS should be suspected during recurrent
      symptoms after spinal fusion surgery. Evaluation should be based on the results
      of 18FDG PET scan and surgery. CONCLUSION: Bacterial and histopathological
      analyses combined with an increase of spine fixation and adapted antimicrobial
      therapy are a safe management for ALS.

PMID- 29448994
TI  - Automatic untargeted metabolic profiling analysis coupled with Chemometrics for
      improving metabolite identification quality to enhance geographical origin
      discrimination capability.
AB  - Untargeted metabolic profiling analysis is employed to screen metabolites for
      specific purposes, such as geographical origin discrimination. However, the data
      analysis remains a challenging task. In this work, a new automatic untargeted
      metabolic profiling analysis coupled with a chemometric strategy was developed to
      improve the metabolite identification results and to enhance the geographical
      origin discrimination capability. Automatic untargeted metabolic profiling
      analysis with chemometrics (AuMPAC) was used to screen the total ion
      chromatographic (TIC) peaks that showed significant differences among the various
      geographical regions. Then, a chemometric peak resolution strategy is employed
      for the screened TIC peaks. The retrieved components were further analyzed using
      ANOVA, and those that showed significant differences were used to build a
      geographical origin discrimination model by using two-way encoding partial least
      squares. To demonstrate its performance, a geographical origin discrimination of
      flaxseed samples from six geographical regions in China was conducted, and 18 TIC
      peaks were screened. A total of 19 significant different metabolites were
      obtained after the peak resolution. The accuracy of the geographical origin
      discrimination was up to 98%. A comparison of the AuMPAC, AMDIS, and XCMS
      indicated that AuMPACobtained the best geographical origin discrimination
      results. In conclusion, AuMPAC provided another method for data analysis.

PMID- 29448995
TI  - A stochastic view on column efficiency.
AB  - A stochastic model of transcolumn eddy dispersion along packed beds was derived.
      It was based on the calculation of the mean travel time of a single analyte
      molecule from one radial position to another. The exchange mechanism between two
      radial positions was governed by the transverse dispersion of the analyte across
      the column. The radial velocity distribution was obtained by flow simulations in
      a focused-ion-beam scanning electron microscopy (FIB-SEM) based 3D reconstruction
      from a 2.1 mm * 50 mm column packed with 2 MUm BEH-C18 particles. Accordingly,
      the packed bed was divided into three coaxial and uniform zones: (1) a 1.4
      particle diameter wide, ordered, and loose packing at the column wall (velocity
      uw), (2) an intermediate 130 MUm wide, random, and dense packing (velocity ui),
      and (3) the bulk packing in the center of the column (velocity uc). First, the
      validity of this proposed stochastic model was tested by adjusting the predicted
      to the observed reduced van Deemter plots of a 2.1 mm * 50 mm column packed with
      2 MUm BEH-C18 fully porous particles (FPPs). An excellent agreement was found for
      ui = 0.93uc, a result fully consistent with the FIB-SEM observation (ui =
      0.95uc). Next, the model was used to measure ui = 0.94uc for 2.1 mm * 100 mm
      column packed with 1.6 MUm Cortecs-C18 superficially porous particles (SPPs). The
      relative velocity bias across columns packed with SPPs is then barely smaller
      than that observed in columns packed with FPPs (+6% versus + 7%). uw=1.8ui is
      measured for a 75 MUm * 1 m capillary column packed with 2 MUm BEH-C18 particles.
      Despite this large wall-to-center velocity bias (+80%), the presence of the thin
      and ordered wall packing layer has no negative impact on the kinetic performance
      of capillary columns. Finally, the stochastic model of long-range eddy dispersion
      explains why analytical (2.1-4.6 mm i.d.) and capillary (<400 MUm i.d.) columns
      can all be packed efficiently (1 <hmin< 2) with particles of size larger than 2
      MUm. In contrast, the model predicts that 0.4-1.2 mm i.d. columns and 2.1 mm i.d.
      columns cannot be packed well (hmin>3) with sub-2 MUm particles and with 1 MUm
      particles, respectively.

PMID- 29448997
TI  - Comment on Salt-assisted dispersive liquid-liquid microextraction coupled with
      programmed temperature vaporization gas chromatography-massspectrometry for the
      determination of haloacetonitriles in drinking water.

PMID- 29448996
TI  - Automating data analysis for two-dimensional gas chromatography/time-of-flight
      mass spectrometry non-targeted analysis of comparative samples.
AB  - Non-targeted analysis of environmental samples, using comprehensive two
      dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC
      * GC/ToF-MS), poses significant data analysis challenges due to the large number
      of possible analytes. Non-targeted data analysis of complex mixtures is prone to
      human bias and is laborious, particularly for comparative environmental samples
      such as contaminated soil pre- and post-bioremediation. To address this research
      bottleneck, we developed OCTpy, a PythonTM script that acts as a data reduction
      filter to automate GC * GC/ToF-MS data analysis from LECO(r) ChromaTOF(r)
      software and facilitates selection of analytes of interest based on peak area
      comparison between comparative samples. We used data from polycyclic aromatic
      hydrocarbon (PAH) contaminated soil, pre- and post-bioremediation, to assess the
      effectiveness of OCTpy in facilitating the selection of analytes that have formed
      or degraded following treatment. Using datasets from the soil extracts pre- and
      post-bioremediation, OCTpy selected, on average, 18% of the initial suggested
      analytes generated by the LECO(r) ChromaTOF(r) software Statistical Compare
      feature. Based on this list, 63-100% of the candidate analytes identified by a
      highly trained individual were also selected by OCTpy. This process was
      accomplished in several minutes per sample, whereas manual data analysis took
      several hours per sample. OCTpy automates the analysis of complex mixtures of
      comparative samples, reduces the potential for human error during heavy data
      handling and decreases data analysis time by at least tenfold.

PMID- 29448998
TI  - Cardiac amyloidosis: from clinical suspicion to morphological diagnosis.
AB  - Amyloidosis is a heterogeneous group of diseases characterised by extracellular
      accumulation of amyloid in various tissues and organs of the body, leading to
      alteration and destruction of tissues. Heart involvement is the most important
      prognostic factor in patients with systemic amyloidosis and the diagnosis and
      typing of amyloid must be made properly. The clinical picture shows congestive
      heart failure with predominant right-sided heart failure symptoms in fully
      developed disease, various types of arrhythmias and characteristic
      electrocardiography and echocardiography findings. Blood and urine monoclonal
      protein studies and cardiac biomarkers belong to the spectrum of standard
      laboratory examinations. Cardiac cardiomyopathy is connected with amyloid based
      on immunoglobulin light chains, serum amyloid A, transthyretin, atrial
      natriuretic factor or apolipoprotein A1. In the routine diagnostic algorithm,
      biopsy specimens are examined using special histological staining,
      immunohistochemistry and immunofluorescence; proteomic analysis is only performed
      in specialised centres.

PMID- 29448999
TI  - Quantitative perineural invasion is a prognostic marker in prostate cancer.
AB  - This study aimed to investigate the prognostic value of a quantitative, detailed,
      yet practical analysis of perineural invasion in radical prostatectomy specimens
      in a high-risk prostate cancer cohort. A total of 114 patients with prostate
      cancer who underwent radical prostatectomy between 2000 and 2013 were analysed.
      Using S100 protein immunohistochemistry assisted in the detection of nerves. In
      the area of closest proximity of the tumour to the dorso-lateral margins, nerves
      were counted and the infiltration of nerves was categorised (0-3). Category 0 was
      nerves without immediate tumour-cell-contact. All nerves being fully surrounded
      by tumour (classical perineural carcinosis) were categorised group 3. Two further
      categories discriminated between nerves that were touched either by carcinoma
      cells below 50% of the circumference (category 1) or above (category 2).
      Perineural carcinosis (Pn1) was seen in 61.4% of cases and correlated positively
      with ISUP grades, pT categories and presence of intraductal carcinoma but failed
      significance on Kaplan-Meier analysis. A more quantitative analysis of percentual
      perineural involvement did demonstrate significant survival differences: cases
      with less than one Pn1-positive nerve in 5 high power fields had longer survival
      times. Incomplete perineural involvement (category 1-2) did not have a prognostic
      value, endorsing the current definition of perineural carcinosis as full
      circumferential encasement of a nerve by tumour cells. A quantitative analysis of
      the percentage of nerves positive for perineural invasion has a higher prognostic
      value than the classical dichotomous statement on the mere presence of perineural
      invasion.

PMID- 29449000
TI  - An immunohistochemical and molecular analysis of papillary proliferation of the
      endometrium.
AB  - Papillary proliferations of the endometrium (PPEs) are uncommon lesions that are
      often associated with endometrial polyps. PPEs occasionally precede or co-exist
      with atypical endometrial hyperplasia or adenocarcinoma, but their pathogenesis
      and relationship to endometrial neoplasia is uncertain. In the present study 11
      PPEs, including eight benign papillary proliferations (BPPs) and three complex
      papillary hyperplasias (CPHs) were examined immunohistochemically for expression
      of PAX2, BAF250a, p16, beta-catenin and DNA mismatch repair (MMR) proteins.
      Molecular analysis was also performed on the CPHs using targeted next generation
      sequencing (NGS). All PPEs demonstrated at least one immunohistochemical
      abnormality with altered expression of p16 and PAX2 in nine and seven cases,
      respectively, and beta-catenin in one case. However, none of the cases showed
      loss of BAF250a or MMR protein staining. All CPHs showed KRAS mutations with
      additional mutations in AKT1 and FBXW7 in one case each, and both PIK3CA and
      CTNNB1 in the remaining case. Therefore, PPEs demonstrate immunophenotypical and
      molecular overlap with endometrial endometrioid neoplasia, although loss of
      BAF250a and MMR protein function do not appear to contribute significantly to
      these lesions. KRAS mutations may be important drivers in CPHs but this finding
      needs to be confirmed in larger studies.

PMID- 29449001
TI  - Balance assessment during squatting exercise: A comparison between laboratory
      grade force plate and a commercial, low-cost device.
AB  - Testing balance through squatting exercise is a central part of many
      rehabilitation programs and sports and plays also an important role in clinical
      evaluation of residual motor ability. The assessment of center of pressure (CoP)
      displacement and its parametrization is commonly used to describe and analyze
      squat movement and the laboratory-grade force plates (FP) are the gold standard
      for measuring balance performances from a dynamic view-point. However, the
      Nintendo Wii Balance Board (NWBB) has been recently proposed as an inexpensive
      and easily available device for measuring ground reaction force and CoP
      displacement in standing balance tasks. Thus, this study aimed to compare the
      NWBB-CoP data with those obtained from a laboratory FP during a dynamic motor
      task, such as the squat task. CoP data of forty-eight subjects were acquired
      simultaneously from a NWBB and a FP and the analyses were performed over the
      descending squatting phase. Outcomes showed a very high correlation (r) and
      limited root-mean-square differences between CoP trajectories in anterior
      posterior (r > 0.99, 1.63 +/- 1.27 mm) and medial-lateral (r > 0.98, 1.01 +/-
      0.75 mm) direction. Spatial parameters computed from CoP displacement and ground
      reaction force peak presented fixed biases between NWBB and FP. Errors showed a
      high consistency (standard deviation < 2.4% of the FP outcomes) and a random
      spread distribution around the mean difference. Mean velocity is the only
      parameter which exhibited a tendency towards proportional values. Findings of
      this study suggested the NWBB as a valid device for the assessment and
      parametrization of CoP displacement during squatting movement.

PMID- 29449002
TI  - Shoulder joint kinetics and dynamics during underwater forward arm elevation.
AB  - Aquatic exercises are widely implemented into rehabilitation programs. However,
      both evaluating their mechanical demands on the musculoskeletal system and
      designing protocols to provide progressive loading are difficult tasks. This
      study reports for the first time shoulder joint kinetics and dynamics during
      underwater forward arm elevation performed at speeds ranging from 22.5 to 90
      degrees /s. Net joint moments projected onto anatomical axes of rotation, joint
      power, and joint work were calculated in 18 participants through a novel approach
      coupling numerical fluid flow simulations and inverse dynamics. Joint dynamics
      was revealed from the 3D angle between the joint moment and angular velocity
      vectors, identifying three main functions-propulsion, stabilization, and
      resistance. Speeds <30 degrees /s necessitated little to no power at all, whereas
      peaks about 0.20 W?kg-1 were seen at 90 degrees /s. As speed increased, peak
      moments were up to 61 * higher at 90 than at 22.5 degrees /s, (1.82 +/-
      0.12%BW?AL vs 0.03 +/- 0.01%BW?AL, P < 0.038). This was done at the expense of a
      substantial decrease in the joint moment contribution to joint stability though,
      which goes against the intuition that greater stabilization is required to
      protect the shoulder from increasing loads. Slow arm elevations (<30 degrees /s)
      are advantageous for joint mobility gain at low mechanical solicitation, whereas
      the intensity at 90 degrees /s is high enough to stimulate muscular endurance
      improvements. Simple predictive equations of shoulder mechanical loading are
      provided. They allow for easy design of progressive protocols, either for the
      postoperative shoulder or the conditioning of athlete targeting very specific
      intensity regions.

PMID- 29449003
TI  - Upper partial fibulectomy improves knee biomechanics and function and decreases
      knee pain of osteoarthritis: A pilot and biomechanical study.
AB  - To investigate the change in clinical outcomes and biomechanical properties of
      the knee in response to upper partial fibulectomy. Sixteen patients with medial
      compartment knee osteoarthritis (KOA) underwent upper partial fibulectomy. Visual
      analog scale (VAS) pain, the hospital for special surgery knee score (HSS), hip
      knee-ankle (HKA) angle (measured in the frontal plane), and flexion/extension
      range of motion of the knee were assessed before and up to 6 months after
      surgery. Patients were evaluated for gait parameters and overall peak knee
      adduction moment (KAM). Patient-specific finite element knee models were
      developed to investigate changes in load in response to fibulectomy. Both VAS
      pain and HSS score were significantly improved (P < .001) one day after surgery
      and steadily improved during the subsequent 6 months. HKA angle improved (P =
      .006) immediately and remained stable by 3 months after surgery. A significant
      inverse relationship (R = -0.528, P = .012) between the overall peak KAM
      (decreased by 19.1%) and the HKA (increased by 1.24 degrees  from a more varus to
      more neutral alignment) angle was observed. The minor load supported by the
      fibula preoperatively was spread post-operatively over the cortical bone of the
      tibial shaft. The mean stress in the medial tibial plateau was significantly
      decreased (P < .001), with a portion of the stress transferred to the posterior
      lateral region of the tibial plateau after upper partial fibulectomy. This pilot
      study provides objective 3D gait and plausible biomechanical evidence for the
      improvement in clinical symptoms from partial upper fibulectomy.

PMID- 29449004
TI  - Reply.

PMID- 29449005
TI  - Association between Oxidative Stress, Genetic Factors, and Clinical Severity in
      Children with Sickle Cell Anemia.
AB  - OBJECTIVES: To investigate the associations between several sickle cell disease
      genetic modifiers (beta-globin haplotypes, alpha-thalassemia, and glucose-6
      phosphate dehydrogenase deficiency) and the level of oxidative stress and to
      evaluate the association between oxidative stress and the rates of vaso-occlusive
      events. STUDY DESIGN: Steady-state oxidative and nitrosative stress markers,
      biological variables, genetic modulators, and vaso-occlusive crisis events
      requiring emergency admissions were measured during a 2-year period in 62
      children with sickle cell anemia (58 SS and 4 Sbeta0). Twelve ethnic-matched
      children without sickle cell anemia also participated as healthy controls (AA)
      for oxidative and nitrosative stress level measurement. RESULTS: Oxidative and
      nitrosative stress were greater in patients with sickle cell anemia compared with
      control patients, but the rate of vaso-occlusive crisis events in sickle cell
      anemia was not associated with the level of oxidative stress. The presence of
      alpha-thalassemia, but not glucose-6-phosphate dehydrogenase deficiency or beta
      globin haplotype, modulated the level of oxidative stress in children with sickle
      cell anemia. CONCLUSION: Mild hemolysis in children with alpha-thalassemia may
      limit oxidative stress and could explain the protective role of alpha-thalassemia
      in hemolysis-related sickle cell complications.

PMID- 29449006
TI  - INDESO project: Results from application of remote sensing and numerical models
      for the monitoring and management of Indonesia coasts and seas.

PMID- 29449008
TI  - Tardive dyskinesia: Out of the shadows.
AB  - The approvals of the first two medications, valbenazine and deutetrabenazine, to
      treat tardive dyskinesia have ushered in a new era in neuropsychiatric care.
      Tardive syndromes are defined as delayed onset, persistent movement disorders or
      sensory phenomena that occur in association with exposure to dopamine receptor
      blocking agents (DRBAs). Their underlying pathophysiology remains to be fully
      elucidated, but clinicians can conceptualize tardive syndromes as persistent
      dopamine supersensitivity states. Tardive syndromes can potentially cause
      distress, disfigurement, embarrassment, and dysfunction, and are often permanent.
      Therefore, practitioners who prescribe DRBAs should be aware of this potential,
      carefully assess the risk/benefit ratio when considering the use of these
      medications, and be sure that patients are appropriately informed. Patients on
      DRBAs should be monitored for the development of tardive syndromes, including
      through the use of regularly scheduled Abnormal Involuntary Movement Scale (AIMS)
      (or similar) examinations. Clinicians prescribing DRBAs should be familiar with
      the diagnosis and management of tardive syndromes, and be able to institute
      treatment or refer patients when treatment is appropriate. Future research may
      focus on the potential benefit of earlier introduction of VMAT2 inhibitors to
      delay onset or progression of tardive syndromes. More effective treatments are
      still needed, as are effective, well-tolerated antipsychotics that do not cause
      tardive syndromes.

PMID- 29449007
TI  - Corrigendum to "Argentinean recommendations on the identification of treatment
      failure in relapsing remitting multiple sclerosis patients" [J. Neurol. Sci. 385C
      (2018) 217-224].

PMID- 29449009
TI  - Endemic atypical parkinsonism.

PMID- 29449010
TI  - A brief report of plexiform neurofibroma.
AB  - Plexiform neurofibroma (PNF) is a rare variant of neurofibromatosis type1 (NF-1),
      which histopathologically, is a subtype of benign nerve sheath tumors,
      neurofibromas (NF). It develops as a result of proliferation in all parts of
      peripheral nervous system and can cause the functional damage, deformities, pain,
      considerable mortality, and morbidity and even the increasing risk of malignant
      transformation in some critical cases. Currently, the surgical intervention is
      the treatment of choice for PNF patients, which due to the tumor invasion,
      massive growth, and the chance of postoperative regrowth is not possible. The
      diagnosis of isolated tumor is an uncommon event. Considering the rarity of this
      neoplasm, herein, we describe a case of isolated PNF, so the purpose of this
      presenting is the rarity of recording. We describe a case of isolated plexiform
      neurofibroma presented with 7-year history of a slowly growing postauricular soft
      subcutaneous mass in a 14-year-old boy, which caused the right auricular
      deformity. After initial evaluation by imaging studies, the patient underwent to
      surgical resection of the mass and the diagnosis of plexiform neurofibroma was
      confirmed by histopathologic examination. Surgical excision of the mass had been
      done before which concluded the satisfactory result and based on oncologist
      diagnosis, further intervention such as radiotherapy or chemotherapy was not
      needed. The patient left the hospital with a clinical stability and was suggested
      to continue the regular follow-up. In conclusion, considering neurofibroma (NF)
      as differential diagnosis for subcutaneous masses in head and neck area is
      critical for early diagnosis and treatment procedure.

PMID- 29449011
TI  - EMA recommendation to suspend HES is hazardous.

PMID- 29449013
TI  - Delay in the diagnosis of spinal abscess following epidural analgesia in
      childbirth. When we suspect it?

PMID- 29449012
TI  - Hydroxyethyl starch solutions and patient harm.

PMID- 29449015
TI  - Rapid initiation of guided bone regeneration driven by spatiotemporal delivery of
      IL-8 and BMP-2 from hierarchical MBG-based scaffold.
AB  - Initiation of endogenous repair mechanisms, including key steps of stem cell
      recruitment and cartilage intermediate formation in endochondral ossification, is
      vital to regeneration of large bone defects. To biomimetically promote a rapid
      initiation and ensuing osteogenic stimulation, exogenous chemokine IL-8 and
      growth factor BMP-2 were orchestrated in a mesoporous bioactive glass (MBG)-based
      spatiotemporal delivery system, to achieve a rapid release of IL-8 followed by a
      long-term sustained release of BMP-2. The synergistic effect of IL-8 and BMP-2 on
      initiation stage of bone healing and underlying mechanism were thoroughly
      investigated in vitro and in vivo. Intriguingly, apart from its superiority in
      stem cell recruitment to BMP-2, IL-8 not only endowed a histological "prep-state"
      of endochondral ossification by up-regulating chondrogenic genes and inducing the
      formation of extensive cartilage tissues, facilitating rapid bone transformation
      by BMP-2, but also triggered a cellular "prep-state" with high expression of BMP
      receptors, enhancing the osteoinductivity of BMP-2. With the spatiotemporal
      delivery system, orchestrated signal stimuli of IL-8 and BMP-2 induced a rapid
      initiation including efficient stem cell recruitment and a
      "chondrogenic/osteogenic balance" at the first stage of endochondral
      ossification, and the scaffold facilitated sufficient osteoconductivity, together
      resulting in early extensive bone mineralization and an advanced regeneration
      throughout the repair of large bone defect. We believe this new idea could
      provide insights toward designing bone-repairing biomaterials with higher
      regenerative efficiency.

PMID- 29449014
TI  - Periarticular bone predicts knee osteoarthritis progression: Data from the
      Osteoarthritis Initiative.
AB  - OBJECTIVE: Osteoarthritis (OA) is a disease with a substantial public health
      burden. Quantitative assessments of periarticular bone may be a biomarker capable
      of monitoring early disease progression. The purpose of this study was to
      evaluate whether measures of periarticular bone associate with longitudinal
      structural progression. METHODS: We conducted a 12-18 months longitudinal study
      using the Osteoarthritis Initiative (OAI). Participants received knee dual-energy
      x-ray absorptiometry (DXA), trabecular magnetic resonance (MR) imaging, and x
      rays. Knee DXAs generated proximal tibial medial:lateral periarticular bone
      mineral density (paBMD) measures. Proximal tibial trabecular MR images were
      assessed for trabecular morphometry: apparent bone volume fraction (BVF),
      trabecular number, thickness, and spacing. Weight-bearing x-rays were assessed
      for medial tibiofemoral joint space narrowing (JSN). Chi-squared analyses
      assessed whether periarticular bone measures were predictive of worsening medial
      tibiofemoral JSN, adjusted for age, sex, and BMI. RESULTS: In all, 444
      participants, mean age 64.2 +/- 9.2 years, BMI 29.5 +/- 4.6kg/m2, and 52% male at
      baseline. Medial JSN (radiographic progression) occurred in 40 participants (9%).
      Higher baseline medial:lateral paBMD, apparent BVF, trabecular number and
      thickness, and lower baseline and decreased trabecular spacing were all
      associated with more progression of JSN in the medial compartment. From lowest to
      highest baseline medial:lateral paBMD quartile groups, 2%, 5%, 11%, and 18% had
      medial JSN progression, respectively, between the 36- and 48-month visits, p
      values = 0.001 and 0.002 unadjusted and adjusted. The rate of change in
      medial:lateral paBMD, apparent BVF, and spacing were associated with more medial
      JSN. For rate of medial:lateral paBMD change from lowest to highest quartile, the
      proportion of each group that experienced medial JSN progression were 5%, 5%,
      11%, and 18%, with an unadjusted and adjusted p-value of 0.005. CONCLUSION:
      Baseline and most rates of periarticular bone change associate with knee OA
      structural progression, highlighting the close relationship between subchondral
      bone and JSN. Future studies should focus on developing these measures as
      predictive and pathophysiological biomarkers, and evaluating their deployment in
      clinical trials testing bone-targeted therapeutics.

PMID- 29449016
TI  - Redox-dependent axial ligand replacement and its functional significance in heme
      bound iron regulatory proteins.
AB  - Iron regulatory proteins (IRPs), regulators of iron metabolism in mammalian
      cells, control the translation of proteins involved in iron uptake, storage and
      utilization by binding to specific iron-responsive element (IRE) sequences of
      mRNAs. Two homologs of IRPs (IRP1 and IRP2) have a typical heme regulatory motif
      (HRM), a consensus sequence found in "heme-regulated proteins". However, specific
      heme binding to HRM has been reported only for IRP2, which is essential for
      oxidative modification and loss of binding to target mRNAs. In this paper, we
      confirmed that IRP1 also specifically binds two molar equivalents of heme, and
      found that the absorption and resonance Raman spectra of heme-bound IRP1 were
      quite similar to those of heme-bound IRP2. This shows that the heme environmental
      structures in IRP1 are close to those of proteins using heme as a regulatory
      molecule. Pulse radiolysis experiments, however, clearly revealed an axial ligand
      exchange from Cys to His immediately after the reduction of the heme iron to form
      a 5-coordinate His-ligated heme in heme-bound IRP2, whereas the 5-coordinate His
      ligated heme was not observed after the reduction of heme-bound IRP1. Considering
      that the oxidative modification is only observed in heme-bound IRP2, but not
      IRP1, probably owing to the structural flexibility of IRP2, we propose that the
      transient 5-coordinate His-ligated heme is a prerequisite for oxidative
      modification of heme-bound IRP2, which functionally differentiates heme binding
      of IRP2 from that of IRP1.

PMID- 29449017
TI  - Why Do Hearing Aids Fail to Restore Normal Auditory Perception?
AB  - Hearing loss is a widespread condition that is linked to declines in quality of
      life and mental health. Hearing aids remain the treatment of choice, but,
      unfortunately, even state-of-the-art devices provide only limited benefit for the
      perception of speech in noisy environments. While traditionally viewed primarily
      as a loss of sensitivity, hearing loss is also known to cause complex distortions
      of sound-evoked neural activity that cannot be corrected by amplification alone.
      This Opinion article describes the effects of hearing loss on neural activity to
      illustrate the reasons why current hearing aids are insufficient and to motivate
      the use of new technologies to explore directions for improving the next
      generation of devices.

PMID- 29449018
TI  - [Guide to university hospital careers in dermatology. The GRENT (Graines Engrais
      Tuteurs - Seed Fertilizer Plant stick) Program].

PMID- 29449019
TI  - ?

PMID- 29449020
TI  - ?

PMID- 29449021
TI  - Effect of matrix metalloproteinase 8 inhibitor on resin-dentin bonds.
AB  - OBJECTIVES: This study investigated the effect of matrix metalloproteinase 8 (MMP
      8) on resin-dentin bonds, assessed the mechanical properties of the interfaces
      over time, and discussed the potential application of MMP-8 inhibitor I (MMP8-I)
      as a specific MMP-8 inhibitor to be incorporated into dental adhesives. METHODS:
      The activation and inhibition of MMP-8 was detected by colorimetric assay. After
      1 day, 6 months and 1 year of storage of Control, MMP8-I, and chlorhexidine (CHX)
      groups, the microtensile bond strengths (MUTBS) were used to evaluate the bond
      strength and failure mode distributions, and nanoleakage analysis was used to
      evaluate the minor scattered silver particles. RESULTS: Colorimetric assay showed
      that the activated MMP-8 was enhanced by adhesive procedures, while it was
      inhibited by the additional treatment of MMP8-I or CHX. Compared with the Control
      and CHX groups, the MMP8-I group had significantly higher bond strength and the
      hybrid layer from the MMP8-I-treated dentin exhibited structural integrity of the
      collagen network and decreased silver nitrate penetration after 1 year of
      storage. SIGNIFICANCE: MMP-8 inhibition I protects against the degradation of
      resin-dentin bonds over time, which is better than broad-scale enzyme inhibitor
      CHX. It shows that MMP8-I may be used in dentistry for preventing collagen
      degradation within hybrid layers to extend the longevity of resin-dentin bonds.

PMID- 29449022
TI  - Expression patterns of claudin-5 and its related signals during luteal regression
      in pseudopregnant rats: The enhanced effect of additional PGF treatment.
AB  - To study the expression patterns of claudin-5 and its related signals during
      luteal regression in rats, a sequential PMSG/hCG treatment paradigm was used to
      obtain a single, well-defined generation of corpus luteum (CL). A total of 35
      rats were treated with one PGF or two PGF at an interval of 24 h from day 7 of
      pseudopregnancy to induce CL regression. Serum and ovaries were collected at 0,
      2, 4, 8 or 24 h after one PGF injection (1 PGF), 2 or 24 h after two PGF
      injections (2 PGF). The serum progesterone level was detected by RIA; the ovarian
      expression of claudin-5, the phosphorylations of STAT3 (p-STAT3), Akt (p-Akt),
      ERK1/2 (p-ERK) and p38 MAPK (p-p38) were detected by western blot, real-time PCR
      and IHC. Results showed that serum progesterone (P4) decreased after PGF
      treatment. Claudin-5 mRNA decreased at 4 h and 8 h after 1 PGF and 2 h after 2
      PGF, and claudin-5 protein decreased at 4 h after 1 PGF. p-STAT3 increased at 4 h
      after 1 PGF and 2 h after 2 PGF. p-ERK increased at 2 h after 2 PGF. The level of
      p-Akt decreased at 4 h after 1 PGF. PGF treatment did not alter the
      phosphorylation of p38 MAPK at any time points in this study. IHC results
      revealed that claudin-5 was expressed in the nuclei and cytoplasm of
      steroidogenic cells and in the vessels, while PGF induced-p-STAT3 was expressed
      uniformly in the cytoplasm of luteal steroidogenic cells. In conclusion, PGF
      treatment decreased the expression of claudin-5 and the additional PGF treatment
      enhanced the decrease in claudin-5 mRNA expression and the increases in ERK1/2
      and STAT3 phosphorylation in the corpus luteum of pseudopregnant rats, which will
      contribute new information to the further study of molecular mechanism of luteal
      regression.

PMID- 29449023
TI  - Healthcare-associated infections studies project: An American Journal of
      Infection Control and National Healthcare Safety Network data quality
      collaboration: Location mapping.
AB  - This case study is part of a series centered on the Centers for Disease Control
      and Prevention/National Healthcare Safety Network (NHSN) health care-associated
      infection (HAI) surveillance definitions. This specific case study focuses on
      appropriately mapping locations within an NHSN-enrolled facility. The intent of
      the case study series is to foster standardized application of the NHSN HAI
      surveillance definitions among IPs and encourage accurate determination of HAI
      events. An online survey link is provided where participants may confidentially
      answer questions related to the case study and receive immediate feedback in the
      form of correct answers and explanations and rationales. Details of the case
      study, answers, and explanations have been reviewed and approved by NHSN staff.
      We hope that participants take advantage of this educational offering and thereby
      gain a greater understanding of NHSN HAI surveillance definitions.

PMID- 29449024
TI  - Surrogate Alcohol or Nonbeverage Alcohol Consumption: The Surrogate Alcohol
      Questionnaire (SAQ).
AB  - BACKGROUND: Diagnosis and treatment of alcohol use disorders and their sequelae
      are common clinical questions for the consultation-liaison psychiatrist. At an
      urban, academic medical center, the authors consulted on several patients whose
      consumption of alcohol included nonbeverage forms of alcohol, (described in the
      literature as surrogate alcohols, nonbeverage alcohols, e.g., mouthwash).
      METHODS: The authors describe 4 patients who presented with surrogate alcohol
      consumption. The authors review the clinical issues and literature related to
      surrogate alcohol use. The authors describe the array of substances, which either
      contain ethanol, but are not intended for drinking, or which contain other
      intoxicating alcohols (e.g., methanol), that are consumed in lieu of traditional
      beverage alcohol. Furthermore, the authors discuss standard medical treatment
      interventions for ethanol and non-ethanol based alcohols. The authors propose a
      screening tool, the surrogate alcohol questionnaire, a tool to facilitate better
      recognition of surrogate alcohol use.

PMID- 29449025
TI  - [Prospective, monocentric, uncontrolled study of efficacy, tolerance and
      adherence of cyclosporin 0.1 % for severe dry eye syndrome].
AB  - PURPOSE: To evaluate the efficacy, tolerability and treatment adherence of
      Ikervis(r) (Santen, SAS) (ciclosporine 0.1 %) for first line therapy or following
      treatment with Restasis(r) (Allergan, Inc.) (ciclosporine 0.05 %) for severe dry
      eye syndrome. MATERIAL AND METHODS: A prospective, monocentric, uncontrolled
      study was conducted between January 2012 and March 2015 on 110 eyes of 55
      patients with severe dry eye on first line therapy or previously treated with
      Restasis(r) who required the introduction of Ikervis(r). Patients' quality of
      life was assessed before and after treatment was started using a standardized
      questionnaire (Ocular Surface Disease Index(c) [OSDI]), clinical efficacy was
      quantified at the slit lamp, by measurement of the Break Up time Test (BUT) and
      the Oxford classification. Tolerability and adherence to treatment were measured
      using a simple questionnaire. RESULTS: A total of 72 eyes of 37 patients were
      included. Etiologies of dry eye syndrome were dominated by Sjogren syndrome (32
      %) and severe ocular surface conditions (48 %). The mean age was 57.7 years (+/
      17.45) and mean follow-up was 458 days (+/-292). The mean BUT increased by
      2.043seconds [1.522-2.563] (P<0.0001). Corneal/conjunctival involvement evaluated
      by the Oxford classification was also improved with a difference in level of 1.68
      [1.290-2.071] (P<0.0001). Ocular Surface Disease Index(c) (OSDI) decreased by
      21.7 [16.372-27.024] (P<0.0001). Treatment tolerability was moderate, with more
      than 50 % of patients experiencing pain on instillation. Overall satisfaction
      with treatment was good, with more than 60 % of patients feeling better after
      initiation of treatment. CONCLUSION: Ikervis(r) is an effective treatment of
      severe dry eye. Its indications tend to evolve towards less severe dry eye.
      However, the tolerability profile remains poor, and an improvement in this would
      be desirable.

PMID- 29449026
TI  - Validity of a single PTSD checklist item to screen for insomnia in survivors of
      critical illness.
AB  - BACKGROUND: There is no insomnia screening tool validated in intensive care unit
      (ICU) survivors. OBJECTIVES: To examine the validity of a single item from the
      PTSD checklist-Civilian version (PCL-C) to detect insomnia by Insomnia Severity
      Index (ISI) METHODS: We performed a secondary analysis of data from a
      longitudinal investigation in 120 medical-surgical ICU survivors. At 1 year post
      ICU, patients completed ISI, PCL-C, and Medical Short-Form 12 (SF-12) by
      telephone. A single PCL-C item rates difficulty initiating or maintaining sleep
      over the past month. We compared performance characteristics of this PCL-C item
      to ISI-defined insomnia (ISI >=15). RESULTS: A score of >=3 on the PCL-C sleep
      item exhibited 91% sensitivity and 67% specificity for ISI-defined insomnia (ISI
      >= 15), and it demonstrated construct validity by correlation to related QOL
      indices. CONCLUSIONS: A single PCL-C sleep item score >= 3 is a reasonable screen
      to identify insomnia symptoms in ICU survivors.

PMID- 29449027
TI  - Suberized transport barriers in Arabidopsis, barley and rice roots: From the
      model plant to crop species.
AB  - Water is the most important prerequisite for life and plays a major role during
      uptake and transport of nutrients. Roots are the plant organs that take up the
      major part of water, from the surrounding soil. Water uptake is related to the
      root system architecture, root growth, age and species dependent complex
      developmental changes in the anatomical structures. The latter is mainly
      attributed to the deposition of suberized barriers in certain layers of cell
      walls, such as endo- and exodermis. With respect to water permeability, changes
      in the suberization of roots are most relevant. Water transport or hydraulic
      conductivity of roots (Lpr) can be described by the composite transport model and
      is known to be very variable between plant species and growth conditions and root
      developmental states. In this review, we summarize how anatomical structures and
      apoplastic barriers of roots can diversely affect water transport, comparing the
      model plant Arabidopsis with crop plants, such as barley and rice. Results
      comparing the suberin amounts and water transport properties indicate that the
      common assumption that suberin amount negatively correlates with water and solute
      transport through roots may not always be true. The composition, microstructure
      and localization of suberin may also have a great impact on the formation of
      efficient barriers to water and solutes.

PMID- 29449029
TI  - Development of alcohol expectancies and early alcohol use in children and
      adolescents: A systematic review.
AB  - PURPOSE: Developmental changes in alcohol expectancies (AE) have been proposed to
      lead to alcohol use initiation and later alcohol use in adolescence. This
      systematic review aims to provide longitudinal evidence of the development of AE
      and the relation of AE to alcohol outcomes from childhood to late adolescence (4
      18 years old). METHODS: A computer-assisted search of relevant articles
      identified 1602 studies, of which 43 studies (conducted between 1996 and 2016)
      were selected. RESULTS: First, negative AE decline and positive AE increase in
      early adolescence. Moreover, alcohol use (initiation) seems to strongly influence
      changes in AE. Second, AE predict alcohol use initiation and drinking patterns
      over time. Third, longitudinal predictors of AE could be divided into individual
      predictors (i.e., alcohol-related cognitions, psychopathology, and genetics) and
      environmental predictors (i.e., family, peer, and media influences). Lastly, the
      results indicated that AE function as mediators of the relations between the
      various individual and environmental predictors and adolescent's alcohol use.
      CONCLUSIONS: Alcohol expectancies form an important framework through which
      drinking behavior can be explained over time. Due to the diverse findings on the
      predictors of AE, future longitudinal studies should further clarify the factors
      that are essential in the development of AE and adolescent's later alcohol use.

PMID- 29449028
TI  - ?
AB  - The development and the access to collections of human biological samples is one
      of the major challenges for health research. In recent years, biological resource
      centres (BRCs) have developed in such a way that they provide all activities
      relating to the handling of samples. In this context, France is undoubtedly a
      pioneering country, because most of the biological collections available were
      created on the basis of themed research projects, which involved a particular
      donor phenotype. The round table was an opportunity to emphasise the persistence
      of some pitfalls particularly in relation to ensuring the consistency of
      different regulatory pathways. It also gave the opportunity to question and make
      recommendations on aspects of governance of biological collections and the BRCs,
      to state the challenges linked to scientific and economic valorisation and to
      consider the place of patients and the general public. The development of
      specific education in public health and research is essential to underline that
      these initiatives are necessary for developing new diagnostic and therapeutic
      procedures.

PMID- 29449030
TI  - The frequency of the C9orf72 expansion in a Brazilian population.
AB  - G4C2 hexanucleotide repeat expansions in the C9orf72 gene seem to be the cause of
      numerous cases of amyotrophic lateral sclerosis (ALS) and/or frontotemporal
      dementia (FTD). In this study, we investigated the presence of the G4C2 repeat
      expansion in 463 Brazilian probands, of whom 404 had ALS/motor neuron disease and
      67 FTD, and in 63 healthy controls in the southeastern region of Brazil. The
      highest frequencies of the C9orf72 mutation were in the ALS-FTD group (50% of
      familial and 17.6% of sporadic cases), although it was also present in 5% of pure
      ALS/motor neuron disease patients (11.8% of familial and 3.6% of sporadic cases)
      and in 7.1% of pure familial FTD. Among G4C2 repeat mutation carriers, 68.8% of
      the subjects who developed dementia symptoms were females. This frequency was
      significantly higher than the percentage reached by men with C9orf72 expansion
      who had this phenotype (p = 0.047). No abnormal repeat expansion was found in
      control groups. Inclusion of the C9orf72 genetic test in the molecular panels for
      Brazilian populations with these neurodegenerative diseases should be strongly
      considered.

PMID- 29449031
TI  - Re: Repair of Damaged Ligaments with Tissue Fixation System Minisling Is
      Sufficient to Cure Major Prolapse in All Three Compartments: 5-yr Data.

PMID- 29449032
TI  - Re: Extracorporeal Shock Wave Therapy (ESWT) in Urology: A Systematic Review of
      Outcome in Peyronie's Disease, Erectile Dysfunction, and Chronic Pelvic Pain.

PMID- 29449033
TI  - Overactive Bladder: Advancement or More of the Same.

PMID- 29449034
TI  - Quality of experience during horticultural activities: an experience sampling
      pilot study among older adults living in a nursing home.
AB  - Horticulture was shown to represent a well-being source for older adults,
      encompassing the physical, mental and social domains. Aim of this pilot study was
      to contribute to extant literature through the investigation of the quality of
      experience associated with horticultural versus occupational activities. A group
      of 11 older residents of a nursing home were involved in a crossover study with a
      baseline measure. Participants attended weekly horticultural and occupational
      sessions for two six-week cycles. Experience Sampling Method was administered
      before the program and after each session, to assess participants' levels of
      happiness, concentration, sociability, involvement, challenges and stakes, and
      self-satisfaction. Altogether, 332 self-report questionnaires were collected.
      Findings showed that participants' levels of the cognitive and motivational
      variables increased during both activities, but horticulture was also perceived
      as providing higher challenges and stakes, and improving self-satisfaction.
      Results can have practical implications for well-being promotion among older
      adults through meaningful activity engagement.

PMID- 29449035
TI  - Usage of density analysis based on micro-CT for studying lung injury associated
      with burn-blast combined injury.
AB  - BACKGROUND: Burn-blast combined injury is a kind of injury caused by heat and
      blast at the same time. The lung injury after burn-blast combined injuries is of
      primary importance, and investigation of lung injury is needed in the clinical
      care of patients. Computed tomography (CT) is one of the standard tools used to
      observe the anatomical basis and pathophysiology of acute lung injury. METHODS:
      We applied a method of fast 3D (three-dimensional) reconstruction to calculate
      the density value of the lung injury by CT analysis. Blast-injury group (BL
      group), burn-injury group (B group), burn-blast combined injury group (BBL
      group), and sham control group (C group) were established. Each group had 16
      rats. The three-dimensional images of the lung tissue were obtained at 6h, 24h,
      and 48h according to the CT value. The average density of the whole lung, left
      lung, and right lung were measured. The lung tissues were paraffin-embedded and
      HE stained. Smith scoring was performed according to the pathological findings.
      RESULTS: In the BBL group, the density of the lung tissue was higher than those
      of the BL group and B group (P<0.01). The lung tissue density values at 24h after
      injury were higher than those at 6h and 48h after injury (P<0.01). Pathological
      results confirmed the changes of density analysis of the lung tissue. CONCLUSION:
      The results have indicated that density analysis through a CT scan can be used as
      a way to evaluate lung injury in a burn-blast injury.

PMID- 29449036
TI  - Vitelliform retinopathy associated with breast cancer.

PMID- 29449037
TI  - Impact of light irradiation on preservation and function of mammalian
      spermatozoa.
AB  - Light irradiation has been demonstrated to exert positive effects on gametes, and
      particularly on sperm. In effect, a high number of studies conducted in several
      species, including humans, mice, pigs, cattle and sheep, and using different
      light sources (such as lasers and light-emitting diodes) have demonstrated that
      photo-stimulation increases sperm motility. In addition, other works have shown
      that sperm fertilizing ability both in vitro and in vivo can be increased
      following light irradiation; there are also some evidences pointing out to an
      extend of lifespan of preserved semen. Notwithstanding, no study has reported a
      detrimental effect of visible light on DNA integrity. The mechanisms through
      which light exerts its effects are not completely elucidated, but mounting
      evidence gives cell photosensitizers, especially those present in the
      mitochondria, a vital role. Stimulating these molecules turns into an increase in
      the production of ATP and Ca2+ influx, which contributes to explain the effects
      of light upon spermatozoa. Additionally, the presence of opsins in spermatozoa as
      well as the potential influence of light on the conformation of other proteins
      may also be involved in the sperm response to light. However, there are still a
      significant number of points that need to be addressed and their elucidation may
      contribute to increase the utilization of light irradiation for sperm
      preservation and ART.

PMID- 29449038
TI  - One year daily changes in fecal sexual steroids of two captive female cheetahs
      (Acinonyx jubatus) in Italy.
AB  - The present study evaluated changes of fecal sexual steroids in two female
      cheetahs (Geijsha and Duchessa) in Northern Italy throughout one year. Wet feces
      were collected daily from two sibling animals of the same age, housed with
      conspecific males and managed in the same conditions, and estrogens and
      progestogens concentrations were analyzed by radioimmunoassay (RIA). Evidence of
      ovarian activity based on regular fluctuation in estrogen excretion was
      demonstrated in both females. None of the animals was continuously cycling, as
      follicular activity was interrupted by anestrous periods, during the spring and
      early winter. No significant increases of progestogens were recorded after the
      estrogen peaks, indicating that induced or spontaneous ovulations did not occur
      during the observation period. The wavelet decomposition evidenced the temporal
      pattern of ovarian activity in the two females, underlying throughout the year a
      more pronounced rhythmical ovarian estrogenic activity in Geijsha than in
      Duchessa. However, this statistical approach had a smoothing effect in depicting
      the hormonal patterns and the number of follicular phases might be lower than
      that revealed by the iterative method. In this study, RIA on wet feces performed
      very well to determine sexual steroid concentrations, and an ovarian activity
      interrupted by anestrous periods along the year in captive cheetahs co-housed in
      a small group was demonstrated. More information on estrous behavior of captive
      cheetahs were obtained in this study, but the effects of husbandry and management
      conditions on natural reproductive physiology of this species remain to
      elucidate.

PMID- 29449039
TI  - Clinical guidelines for endoscopic mucosal resection of non-pedunculated
      colorectal lesions.
AB  - This document summarizes the contents of the Clinical Guidelines for the
      Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was
      developed by the working group of the Spanish Society of Digestive Endoscopy
      (GSEED of Endoscopic Resection). This document presents recommendations for the
      endoscopic management of superficial colorectal neoplastic lesions.

PMID- 29449040
TI  - Xenon adsorption on geological media and implications for radionuclide
      signatures.
AB  - The detection of radioactive noble gases is a primary technology for verifying
      compliance with the pending Comprehensive Nuclear-Test-Ban Treaty. A fundamental
      challenge in applying this technology for detecting underground nuclear
      explosions is estimating the timing and magnitude of the radionuclide signatures.
      While the primary mechanism for transport is advective transport, either through
      barometric pumping or thermally driven advection, diffusive transport in the
      surrounding matrix also plays a secondary role. From the study of primordial
      noble gas signatures, it is known that xenon has a strong physical adsorption
      affinity in shale formations. Given the unselective nature of physical
      adsorption, isotherm measurements reported here show that non-trivial amounts of
      xenon adsorb on a variety of media, in addition to shale. A dual-porosity model
      is then discussed demonstrating that sorption amplifies the diffusive uptake of
      an adsorbing matrix from a fracture. This effect may reduce the radioxenon
      signature down to approximately one-tenth, similar to primordial xenon isotopic
      signatures.

PMID- 29449042
TI  - Computed Tomography Imaging of Non-Neoplastic and Neoplastic Benign Gastric
      Disease.
AB  - Gastric disease is a common finding in patients imaged in the emergency
      department, with radiologists encountering more and more benign gastric disease
      on CT. In this case based review, we discuss CT appearance of various benign
      gastric pathology including self-limiting conditions such as gastritis, different
      benign gastric neoplasms, as well as life threatening disorders such as
      perforation, obstruction, and hemorrhage.

PMID- 29449041
TI  - Biomechanical simulation of traumatic brain injury in the rat.
AB  - BACKGROUND: Traumatic brain injury poses an enormous clinical challenge. Rats are
      the animals most widely used in pre-clinical experiments. Biomechanical
      simulations of these experiments predict the distribution of mechanical stress
      and strain across key tissues. It is in theory possible to dramatically increase
      our understanding of traumatic brain injury pathophysiology by correlating stress
      and strain with histological and functional injury outcomes. This review
      summarizes the state of the art in biomechanical simulation of traumatic brain
      injury in the rat. It also places this body of knowledge in the context of the
      wider effort to understand traumatic brain injury in rats and in humans. METHODS:
      Peer-reviewed research articles on biomechanical simulation of traumatic brain
      injury in the rat were reviewed and summarized. FINDINGS: When mathematical
      models of traumatic brain injury in the rat first emerged, they relied on scant
      data regarding biomechanical properties. The data on relevant biomechanical
      properties has increased recently. However, experimental models of traumatic
      brain injury in the rat have also become less homogeneous. New and modified
      models have emerged that are biomechanically distinct from traditional models.
      INTERPRETATION: Important progress in mathematical modeling and measurement of
      biomechanical properties has led to credible, predictive simulations of
      traditional, experimental models of traumatic brain injury in the rat, such as
      controlled cortical impact. However, recent trends such as the increasing
      popularity of closed head models and blast models create new biomechanical
      challenges. Investigators studying rat brain biomechanics must continue to
      innovate to keep pace with these developments.

PMID- 29449043
TI  - The Verigene dilemma: gram-negative polymicrobial bloodstream infections and
      clinical decision making.
AB  - Verigene Blood-Culture Gram-Negative (GN) results in rapid identification of key
      GNs in bloodstream infections. Its use clinically is limited by low sensitivity
      in polymicrobial GN infections and concerns for inappropriate antibiotic
      modification. In a retrospective review of 1003 blood culture sets, the incidence
      of missed GNs was infrequent, <4%, with the potential to negatively impact the
      management of GN BSIs in <2% of cases.

PMID- 29449044
TI  - Emerging pollutants. II International Caparica conference on pollutant toxic ions
      and molecules 2nd PTIM-2017.

PMID- 29449045
TI  - How to measure glucocorticoid receptor's sensitivity in patients with stress
      related psychiatric disorders.
AB  - Stress is a state of derailed homeostasis and a main environmental risk factor
      for psychiatric diseases. Chronic or uncontrollable stress may lead to a
      dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is a common
      feature of stress-related psychiatric disorders. One of the key mechanisms
      underlying a disturbed HPA axis is an impaired function of the glucocorticoid
      receptor (GR) with an enhanced or reduced feedback sensitivity for
      glucocorticoids and subsequently altered concentrations of peripheral cortisol.
      GR function is regulated by a multiprotein complex including the different
      expression of the hsp90 co-chaperone FK 506 binding protein 51 (FKBP5) that may
      be genetically determined or acquired in response to stressful stimuli. Specific
      patterns of a dysregulation of the HPA axis and GR function are found in
      different stress-related psychiatric entities e.g. major depression, job-related
      exhaustion or posttraumatic stress disorder. GR challenge tests like the
      dexamethasone-suppression test (DST), the dexamethasone-corticotropin-releasing
      hormone (dex-CRH) test or most recently the analysis of the dexamethasone-induced
      gene expression are employed to sensitively measure HPA axis activity in these
      disorders. They provide information for a stratification of phenotypic similar
      but neurobiological diverse psychiatric disorders. In this review we present a
      synopsis of GR challenge tests with a focus on the application of the DST, the
      CRH test and the dex-CRH test as well as the dexamethasone-induced gene
      expression in stress-related psychiatric entities.

PMID- 29449046
TI  - [Chordoma cutis, an unusual clinical presentation of a rare neoplasm: Chordoma].
AB  - Chordoma cutis represents an unusual clinical presentation of a rare neoplasm.
      The involvement of skin or sub-cutaneous soft tissues can be the consequence of
      local infiltration or metastasis; the latter may occur several years following
      the initial diagnosis of chordoma and therefore, may pose a diagnosis challenge
      when the clinical history of the patient is unknown. The clinical forms,
      morphology, immuno-histochemical profile and the main differential diagnoses of
      chordoma cutis are presented here through an anatomoclinical case.

PMID- 29449048
TI  - Borrelia burgdorferi sl and tick-borne encephalitis virus coinfection in Eastern
      France.

PMID- 29449047
TI  - Validation and update of a lymph node metastasis prediction model for breast
      cancer.
AB  - PURPOSE: This study aimed to validate and update a model for predicting the risk
      of axillary lymph node (ALN) metastasis for assisting clinical decision-making.
      METHODS: We included breast cancer patients diagnosed at six Dutch hospitals
      between 2011 and 2015 to validate the original model which includes six
      variables: clinical tumor size, tumor grade, estrogen receptor status, lymph node
      longest axis, cortical thickness and hilum status as detected by ultrasonography.
      Subsequently, we updated the original model using generalized linear model (GLM)
      tree analysis and by adjusting its intercept and slope. The area under the
      receiver operator characteristic curve (AUC) and calibration curve were used to
      assess the original and updated models. Clinical usefulness of the model was
      evaluated by false-negative rates (FNRs) at different cut-off points for the
      predictive probability. RESULTS: Data from 1416 patients were analyzed. The AUC
      for the original model was 0.774. Patients were classified into four risk groups
      by GLM analysis, for which four updated models were created. The AUC for the
      updated models was 0.812. The calibration curves showed that the updated model
      predictions were better in agreement with actual observations than the original
      model predictions. FNRs of the updated models were lower than the preset 10% at
      all cut-off points when the predictive probability was less than 12.0%.
      CONCLUSIONS: The original model showed good performance in the Dutch validation
      population. The updated models resulted in more accurate ALN metastasis
      prediction and could be useful preoperative tools in selecting low-risk patients
      for omission of axillary surgery.

PMID- 29449049
TI  - Extended-spectrum beta-lactamase-producing Enterobacteriaceae, national study of
      antimicrobial treatment for pediatric urinary tract infection.
AB  - OBJECTIVE: To evaluate clinical practices for ESBL-producing urinary tract
      infection (UTI) in France. METHODS: We performed an observational, retrospective,
      cross-sectional, hospital-based study in 22 pediatric departments of university
      or secondary care hospitals. We collected data of the last five patients
      presenting with ESBL-producing UTI in 2012 and the physicians' therapeutic
      approach to two case vignettes of acute non-septic ESBL-producing pyelonephritis
      (7-month-old girl) and cystitis (30-month-old girl). The adequacy of the
      therapeutic decision was analyzed by a panel of independent infectious disease
      experts. RESULTS: A total of 80 case patients of ESBL-producing UTI were
      collected: 54 with acute pyelonephritis (mean age: 28 months, female: 66%), of
      whom 98% received an intravenous ESBL-adapted antibiotic treatment and 55% a two
      drug antibiotic therapy. Carbapenems were used in 56% of cases and
      aminoglycosides in 36%. Of the 26 cystitis patients (mean age: 5 years, female:
      73%), 85% were treated with antibiotics, including three intravenously
      (carbapenems=2). For the case vignettes, physicians (n=85) would have treated the
      pyelonephritis patient with carbapenems (76%) and/or aminoglycosides (68%); 71%
      would have used a two-drug antibiotic treatment. The cystitis patient would have
      been treated intravenously by 29% of physicians; 8% would have used a two-drug
      antibiotic treatment, 16% would have prescribed carbapenems, and 11%
      aminoglycosides. Antibiotic treatments were deemed appropriate in 37% of cases.
      CONCLUSIONS: Antimicrobial treatment for ESBL-producing UTI greatly varies, and
      carbapenems are excessively prescribed. Specific guidelines for ESBL infections
      are required.

PMID- 29449050
TI  - A novel truncating mutation in FLNA causes periventricular nodular heterotopia,
      Ehlers-Danlos-like collagenopathy and macrothrombocytopenia.
AB  - INTRODUCTION: Filamin A (FLNA) is located in Xq28, and encodes the actin binding
      protein, filamin A. A mutation in FLNA is the most common cause of
      periventricular nodular heterotopia (PVNH), but a clear phenotype-genotype
      correlation has not been established. Indeed, some patients with a FLNA mutation
      have recently been shown to additionally have Ehlers-Danlos-like collagenopathy
      or macrothrombocytopenia. In an attempt to establish a clearer correlation
      between clinical symptoms and genotype, we have investigated a phenotype that
      involves thrombocytopenia in a patient with a truncation of the FLNA gene. CASE
      REPORT: We present the case of a 4-year-old girl who, at birth, showed a ventral
      hernia. At 2 months of age, she was diagnosed with patent ductus arteriosus (PDA)
      and aortic valve regurgitation. At 11 months, she underwent ligation of the PDA.
      She was also diagnosed with diaphragmatic eventration by a preoperative test. At
      19 months, motor developmental delay was noted, and brain MRI revealed bilateral
      PVNH with mega cisterna magna. Presently, there is no evidence of epilepsy,
      intellectual disability or motor developmental delay. She has chronic, mild
      thrombocytopenia, and a platelet count that transiently decreases after viral
      infection. Dilation of the ascending aorta is progressing gradually. Genetic
      testing revealed a de novo nonsense heterozygous mutation in FLNA (NM_001456.3:
      c.1621G > T; p.Glu541Ter). Immunofluorescence staining of a peripheral blood
      smear showed a lack of filamin A expression in 21.1% of her platelets. These
      filamin A-negative platelets were slightly larger than her normal platelets.
      CONCLUSION: Our data suggests immunofluorescence staining of peripheral blood
      smears is a convenient diagnostic approach to identify patients with a FLNA
      mutation, which will facilitate further investigation of the correlation between
      FLNA mutations and patient phenotype.

PMID- 29449052
TI  - Response to: Bordetella Pertussis in hajj pilgrims.

PMID- 29449051
TI  - Differences in the validity of a visual estimation method for determining
      patients' meal intake between various meal types and supplied food items.
AB  - BACKGROUND & AIMS: The aim of this study was to examine differences in the
      validity of a visual estimation method for determining patients' meal intake
      between various meal types and supplied food items in hospitals and to find
      factors influencing the validity of a visual estimation method. METHODS: There
      are two procedures by which we obtained the information on dietary intake of the
      patients in these hospitals. These are both by visual assessment from the meal
      trays at the time of their clearing, by the attending nursing staff and by
      weighing conducted by researchers. The following criteria are set for the target
      trays: A) standard or therapeutic meals, which are monitored by a doctor, for
      energy and/or protein and/or sodium; B) regular, bite-sized, minced and pureed
      meal texture, and C) half-portion meals. Visual assessment results were tested
      for their validity by comparing with the corresponding results of weighing.
      Differences between these two methods indicated the estimated and absolute values
      of nutrient intake. RESULTS: A total of 255 (76.1%) trays were included in the
      analysis out of the 335 possible trays and the results indicated that the energy
      consumption estimates by visual or weighing procedures are not significantly
      different (412 +/- 173 kcal, p = 0.15). However, the mean protein consumption was
      significantly different (16.3 +/- 6.7 g/tray, p < 0.01) between the two
      procedures. Compared with standard meals (38 +/- 45 kcal, 1.9 +/- 2.5 g/tray),
      raters significantly misestimated the energy and protein intake of half-portion
      meals (78 +/- 65 kcal, 2.8 +/- 2.2 g/tray, p = 0.01) but accurately estimated the
      protein intake of protein controlled meals (0.5 +/- 0.6 g/tray, p = 0.03). Trays
      adding supplied food items were significantly misestimated for energy intake (66
      +/- 58 kcal/tray) compared to trays with no additions (32 +/- 39 kcal/tray, p <
      0.01). Moreover, the results of multivariable analysis demonstrated that supplied
      food items were significantly associated with increased odds of a difference
      between the two methods (OR: 3.84; 95% confidence interval [CI]: 1.07-13.85).
      CONCLUSIONS: There were high correlations between the visual estimation method
      and the weighing method measuring patients' dietary intake for various meal types
      and textures, except for meals with added supplied food items. Nursing staff need
      to be attentive to supplied food items.

PMID- 29449053
TI  - Genetic and epigenetic alterations in the tumour, tumour margins, and normal
      buccal mucosa of patients with oral cancer.
AB  - Despite adequate surgical resection, oral squamous cell carcinoma (OSCC) shows a
      high rate of recurrence and metastasis, which could be explained by the presence
      of molecular alterations in seemingly normal tumour margins and the entire oral
      mucosa. The aims of this study were (1) to assess the presence of gene
      amplification (c-Myc and HER2) and promoter methylation (p14 and p16) in the
      tumours, tumour margins, and unaffected oral mucosa of 40 OSCC patients, and (2)
      to evaluate the possibility of using these alterations as prognostic markers. c
      Myc and HER2 genes were quantified by means of real-time PCR (qPCR), and p14 and
      p16 methylation status was determined by methylation-specific PCR (MSP PCR). All
      tissues examined exhibited molecular alterations in various proportions. Tumour
      tissues, as expected, showed the highest prevalence of alterations, while oral
      mucosa showed the lowest. Multiple alterations (co-alterations) in tumours and
      tumour margins were significantly more frequent than in unaffected oral mucosa
      (P<0.001 and P=0.027, respectively). HER2 amplification in margin tissue
      (P<0.001) and swabs (P=0.013), as well as the existence of three co-alterations
      in margins (P=0.001) and macroscopically unaffected oral mucosa (P<0.001) were
      correlated with shorter disease-specific survival.

PMID- 29449054
TI  - Second generation antipsychotic-induced mitochondrial alterations: Implications
      for increased risk of metabolic syndrome in patients with schizophrenia.
AB  - Metabolic syndrome (MetS) is seen more frequently in persons with schizophrenia
      than in the general population, and these metabolic abnormalities are further
      aggravated by second generation antipsychotic (SGA) drugs. Although the
      underlying mechanisms responsible for the increased prevalence of MetS among
      patients under SGA treatment are not well understood, alterations in mitochondria
      function have been implicated. We performed a comprehensive evaluation of the
      role of mitochondrial dysfunction in the pathophysiology of drug-induced MetS in
      schizophrenia. We found a downregulation in genes encoding subunits of the
      electron transport chain complexes (ETC), enzyme activity, and mitochondrial
      dynamics in peripheral blood cells from patients at high-risk for MetS.
      Additionally, we evaluated several markers of energy metabolism in lymphoblastoid
      cell lines from patients with schizophrenia and controls following exposure to
      antipsychotics. We found that the high-risk drugs clozapine and olanzapine
      induced a general down-regulation of genes involved in the ETC, as well as
      decreased activities of the corresponding enzymes, ATP levels and a significant
      decrease in all the functional parameters of mitochondrial oxygen consumption in
      cells from patients and controls. We also observed that the medium-risk SGA
      quetiapine decreased oxygen consumption and respiratory control ratio in controls
      and patients. Additionally, clozapine and olanzapine induced a downregulation of
      Drp1 and Mfn2 both in terms of mRNA and protein levels. Together, these data
      suggest that an intrinsic defect in multiple components of oxidative metabolism
      may contribute to the increased prevalence of MetS in patients under treatment
      with SGAs known to cause risk for MetS.

PMID- 29449055
TI  - Adjunctive antidepressants in bipolar depression: A cohort study of six- and
      twelve-months rehospitalization rates.
AB  - Although antidepressants (ADs) are widely used in bipolar depression, there is
      weak evidence for their effectiveness and safety in this condition. Furthermore,
      there is a paucity of studies on the risk-benefit ratio of AD maintenance
      treatment in bipolar disorder (BD). We compared rehospitalization rates of
      patients with BD-I depressive episode who were discharged with mood stabilizers
      (MSs) and/or atypical antipsychotics (AAPs) with or without adjunctive AD. Ninety
      eight patients with BD-I who were hospitalized with a depressive episode between
      2005 and 2013 were retrospectively followed for 6-months and 1-year
      rehospitalization rates, as well as time to rehospitalization, according to
      treatment at discharge: MSs and/or AAPs with or without AD. Multivariable
      survival models adjusted for covariates known to influence rehospitalization were
      conducted. Six-months and 1-year rehospitalization rates were significantly lower
      in the adjunctive-AD treatment group compared to the no-AD group (9.2% vs. 36.4%,
      P = .001, power = 0.87 and 12.3% vs. 42.4%, P = .001, power = 0.89,
      respectively). Time to rehospitalization within 6-months and 1-year was
      significantly longer in the adjunctive-AD treatment group (169.9 vs 141 days, P =
      .001 and 335.6 vs 252.3 days, P = .001, respectively). Adjunctive-AD treatment at
      discharge reduced significantly the adjusted risk of rehospitalization within 6
      months (HR = 0.081, 95% CI: 0.016-0.412, P = 0.002) and 1-year (HR = 0.149, 95%
      CI: 0.041-0.536, P = 0.004). Moreover, adjunctive-AD treatment did not increase
      rehospitalization rates of manic episode. In conclusion, adjunctive-AD therapy to
      MS/AAP at discharge from BD-I depressive episode hospitalization is associated
      with a lower rate of and a longer time to rehospitalization during a 1-year
      follow up period.

PMID- 29449056
TI  - Current Practice of Whole Brain Radiotherapy in Metastatic Non-small Cell Lung
      Cancer.

PMID- 29449057
TI  - Prognostic Significance of Human Papilloma Virus and p16 Expression in Patients
      with Vulvar Squamous Cell Carcinoma who Received Radiotherapy.
AB  - AIMS: Human papilloma virus (HPV) has been identified as an aetiological agent in
      a subset of patients with vulvar squamous cell carcinoma (VSCC). The prognostic
      role of HPV status in VSCC patients treated with radiotherapy has not yet been
      determined. We investigated the associations between HPV, p16 and clinical
      outcome in these women. MATERIALS AND METHODS: Patients undergoing potentially
      curative radiation treatment for VSCC at a single institution from 2000 to 2009
      were retrospectively identified. Those who received definitive or peri-operative
      radiotherapy as part of treatment, and who had available pathological specimens,
      were included for analysis. HPV infection was detected using Roche Linear array
      hybridisation and p16 by immunohistochemistry. The locoregional relapse (LRR)
      rate was estimated using a cumulative incidence function to account for competing
      risks. Disease-free survival (DFS) and overall survival were analysed using the
      Kaplan-Meier method. The median follow-up was 4.9 years. RESULTS: Forty patients
      were suitable for analysis, with a median age of 69.5 years. HPV was detected in
      14/40 (35%) patients, HPV16 being the most common serotype (79%). Patients with
      HPV-positive tumours had lower 5 year LRR compared with those with HPV-negative
      tumours (14.3% versus 79.3%, Gray test P = 0.003). Tumour p16 positivity was also
      associated with lower 5 year LRR (15.4% versus 81.2%, Gray test P = 0.002).
      Patients with p16-positive tumours had higher 5 year DFS compared with those with
      p16-negative tumours (62% versus 7%, Log-rank test P = 0.02). CONCLUSIONS: We
      have identified a favourable prognostic group in VSCC, with p16-positive patients
      showing improved outcomes. p16 has the potential to be a predictive marker
      allowing the identification of women more likely to have a favourable response to
      radiotherapy.

PMID- 29449058
TI  - [Epidemiology of lower extremity artery disease].
AB  - It is estimated that more than 200 million individuals are affected by lower
      extremity artery disease (LEAD) worldwide. This prevalence has increased between
      2000 and 2010 by 25%, especially in low/middle income countries. In France, about
      one million people are affected by this condition. Almost two-thirds of patients
      with LEAD are asymptomatic. This explains the interest of the measurement of the
      ankle-brachial index (ABI), an objective and harmless diagnostic tool. An
      ABI<=0.90 is considered as diagnostic for LEAD. The detection of symptomatic LEAD
      requires standardized questionnaires identifying intermittent claudication.
      Epidemiological studies on chronic limb-threatening ischemia (CLTI) - the most
      severe presentation of the disease - are scarce: the prevalence is estimated
      around 0.5-2.0% after the age of 40, mostly affecting elderly people. Similar to
      other atherosclerotic diseases, the risk factors are multiple (genetic factors,
      traditional risk factors, metabolic and inflammatory factors, socioeconomic
      factors), with different weighs of association as compared to coronary artery
      diseases. Due to their high prevalence and strength of association, cigarette
      smoking and hypertension are the most frequent purveyors of this disease in
      population. Diabetes mellitus is a strong risk factor, and its increasing
      prevalence contributes to the global epidemics of LEAD. In claudicants, the 5
      year amputation risk is estimated at 5%, increasing to 25% at one year in case of
      CLTI. However, the main risk is related to general cardiovascular events. It is
      estimated that patients with LEAD present concomitantly coronary and
      cerebrovascular disease in respectively 50% and 20% of cases. The non
      cardiovascular mortality, especially related to cancer, is also higher than in
      general population. Overall, the control of traditional risk factors has a
      beneficial effect both for the limb and general prognosis.

PMID- 29449059
TI  - Benefit of the nivolumab and ipilimumab combination in pretreated advanced
      melanoma.

PMID- 29449060
TI  - The aprosody of schizophrenia: Computationally derived acoustic phonetic
      underpinnings of monotone speech.
AB  - OBJECTIVE: Acoustic phonetic methods are useful in examining some symptoms of
      schizophrenia; we used such methods to understand the underpinnings of aprosody.
      We hypothesized that, compared to controls and patients without clinically rated
      aprosody, patients with aprosody would exhibit reduced variability in: pitch
      (F0), jaw/mouth opening and tongue height (formant F1), tongue front/back
      position and/or lip rounding (formant F2), and intensity/loudness. METHODS:
      Audiorecorded speech was obtained from 98 patients (including 25 with clinically
      rated aprosody and 29 without) and 102 unaffected controls using five tasks: one
      describing a drawing, two based on spontaneous speech elicited through a question
      (Tasks 2 and 3), and two based on reading prose excerpts (Tasks 4 and 5). We
      compared groups on variation in pitch (F0), formant F1 and F2, and
      intensity/loudness. RESULTS: Regarding pitch variation, patients with aprosody
      differed significantly from controls in Task 5 in both unadjusted tests and those
      adjusted for sociodemographics. For the standard deviation (SD) of F1, no
      significant differences were found in adjusted tests. Regarding SD of F2,
      patients with aprosody had lower values than controls in Task 3, 4, and 5. For
      variation in intensity/loudness, patients with aprosody had lower values than
      patients without aprosody and controls across the five tasks. CONCLUSIONS:
      Findings could represent a step toward developing new methods for measuring and
      tracking the severity of this specific negative symptom using acoustic phonetic
      parameters; such work is relevant to other psychiatric and neurological
      disorders.

PMID- 29449061
TI  - C4A mRNA expression in PBMCs predicts the presence and severity of delusions in
      schizophrenia and bipolar disorder with psychosis.
AB  - Altered immune function is an established finding in psychotic disorders such as
      schizophrenia and bipolar disorder with psychosis, though its role in their
      development and progression remains to be understood. Evidence suggests altered
      JAK-STAT1 pathway activity in peripheral blood cells from participants with
      schizophrenia compared to controls. Activation of this pathway leads to increased
      expression of complement component 4A (C4A), which has recently been implicated
      in schizophrenia. Here, we examine mRNA expression of C4A in peripheral blood
      cells from participants with schizophrenia, bipolar disorder and controls. STAT1
      and IRF-1 mRNA expression are included as measures of JAK-STAT1 pathway
      activation in the same participants. Further, we examine the association of each
      genes mRNA expression with clinical symptom measures using the Positive and
      Negative Syndrome Scale (PANSS) and the Psychotic Symptom Rating Scale (PSYRATS).
      We demonstrate that C4A, STAT1 and IRF-1 mRNA expression levels are correlated
      across the entire sample, indicating shared transcriptional regulatory
      mechanisms. Further, we show that C4A mRNA expression alone is positively
      associated with psychotic symptomatology, specifically the presence and severity
      of delusions. These findings are noteworthy given recent findings that
      demonstrate a critical role for complement proteins in synaptic pruning,
      alterations of which are proposed to contribute to psychopathology in psychosis.

PMID- 29449062
TI  - Acoustic and Perceptual Analyses of Adductor Spasmodic Dysphonia in Mandarin
      speaking Chinese.
AB  - OBJECTIVE: The objective of this study was to examine the perceptual structure
      and acoustic characteristics of speech of patients with adductor spasmodic
      dysphonia (ADSD) in Mandarin. STUDY DESIGN: Case-Control Study MATERIALS AND
      METHODS: For the estimation of dysphonia level, perceptual and acoustic analysis
      were used for patients with ADSD (N = 20) and the control group (N = 20) that are
      Mandarin-Chinese speakers. For both subgroups, a sustained vowel and connected
      speech samples were obtained. The difference of perceptual and acoustic
      parameters between the two subgroups was assessed and analyzed. RESULTS: For
      acoustic assessment, the percentage of phonatory breaks (PBs) of connected
      reading and the percentage of aperiodic segments and frequency shifts (FS) of
      vowel and reading in patients with ADSD were significantly worse than controls,
      the mean harmonics-to-noise ratio and the fundamental frequency standard
      deviation of vowel as well. For perceptual evaluation, the rating of speech and
      vowel in patients with ADSD are significantly higher than controls. The
      percentage of aberrant acoustic events (PB, frequency shift, and aperiodic
      segment) and the fundamental frequency standard deviation and mean harmonics-to
      noise ratio were significantly correlated with the perceptual rating in the vowel
      and reading productions. CONCLUSIONS: The perceptual and acoustic parameters of
      connected vowel and reading in patients with ADSD are worse than those in normal
      controls, and could validly and reliably estimate dysphonia of ADSD in Mandarin
      speaking Chinese.

PMID- 29449063
TI  - Comparison of Post-therapy Dysphonic Voices and Normal Voices.
AB  - PURPOSE: The purpose of the present investigation was to compare the voices of
      post-therapy dysphonic participants with participants who have normal voices to
      determine how close the corrected voices approached normal vocal levels. The
      present investigation is a follow-up to the authors' previous research in which
      dysphonic participants, with voices ranging from moderate-to-severe dysphonia,
      were evaluated pre- and post therapy using the Dysphonic Severity Percentage
      scale and the interval scale. METHODS: In the present study, five raters, three
      speech-language pathologists experienced in assessing dysphonia, and two trained
      speech-language pathology college students evaluated 20 participants with normal
      voices under the same two conditions as those of the corrected participants-when
      reading a paragraph aloud and during spontaneous speech. While listening to the
      recordings of the normal voices, the raters tallied any dysphonic syllables
      produced by the participants to obtain a Dysphonic Severity Percentage for both
      paragraph reading and spontaneous speech. The raters also evaluated the normal
      voices on the interval scale. These data were compared with those of the post
      therapy participants, who were evaluated under the same conditions and methods
      pre- and post therapy. RESULTS AND CONCLUSION: The dysphonic participants' voices
      improved significantly post therapy in comparison with their pretherapy result;
      their improvement, however, was not commensurate with the voices of the normal
      participants, and the data showed a significant difference between the two
      groups. Both evaluation scales reflected a high agreement among raters.

PMID- 29449064
TI  - Pain-related psychological issues in hand therapy.
AB  - STUDY DESIGN: Literature review. INTRODUCTION: Pain is a subjective experience
      that results from the modulation of nociception conveyed to the brain via the
      nervous system. Perception of pain takes place when potential or actual noxious
      stimuli are appraised as threats of injury. This appraisal is influenced by one's
      cognitions and emotions based on her/his pain-related experiences, which are
      processed in the forebrain and limbic areas of the brain. Unarguably, patients'
      psychological factors such as cognitions (eg, pain catastrophizing), emotions
      (eg, depression), and pain-related behaviors (eg, avoidance) can influence
      perceived pain intensity, disability, and treatment outcomes. Therefore, hand
      therapists should address the patient pain experience using a biopsychosocial
      approach. However, in hand therapy, a biomedical perspective predominates in pain
      management by focusing solely on tissue healing. PURPOSE OF THE STUDY: This
      review aims to raise awareness among hand therapists of the impact of pain
      related psychological factors. METHODS AND RESULTS: This literature review
      allowed to describe (1) how the neurophysiological mechanisms of pain can be
      influenced by various psychological factors, (2) several evidence-based
      interventions that can be integrated into hand therapy to address these
      psychological issues, and (3) some approaches of psychotherapy for patients with
      maladaptive pain experiences. DISCUSSION AND CONCLUSION: Restoration of sensory
      and motor functions as well as alleviating pain is at the core of hand therapy.
      Numerous psychological factors including patients' beliefs, cognitions, and
      emotions alter their pain experience and may impact on their outcomes. Decoding
      the biopsychosocial components of the patients' pain is thus essential for hand
      therapists.

PMID- 29449065
TI  - Effects of fluoride and epigallocatechin gallate on soft-drink-induced dental
      erosion of enamel and root dentin.
AB  - BACKGROUND/PURPOSE: Fluoride and epigallocatechin gallate (EGCG) have been proven
      to prevent dental caries. The purpose of this study was to evaluate the effects
      of fluoride and EGCG on soft-drink-induced dental erosion in vitro. METHODS:
      Forty enamel and dentin specimens were prepared from extracted human teeth. The
      specimens were divided into 4 groups and treated separately with distilled water
      (as control), 0.5 M sodium fluoride (NF), 400 MUM EGCG (EG), and a solution
      containing 0.5 M NaF and 400 MUM EGCG (FG). Cyclic erosive treatment was
      performed according to the experimental procedures. The specimens were analyzed
      using laser scanning confocal microscopy, scanning electron microscopy, and a
      microhardness tester. The data were analyzed using ANOVA and Bonferroni's post
      hoc test. The significance level was set at 5%. RESULTS: The amount of substance
      loss was lower in the NF and EG groups than in the control group (p < 0.05). The
      erosion-caused substance loss was more pronounced in the dentin than in the
      enamel specimens. Surface microhardness loss was lower in the NF and EG groups
      than in the control group (p < 0.05). The diameter of the dentinal tubule was
      wider in the control group than in the NF and EG groups (p < 0.05). No combined
      effects were observed in the FG group. CONCLUSION: Both fluoride and EGCG are
      effective in preventing soft-drink-induced erosion compared with the control
      group. Fluoride and EGCG may interfere with each other. The mechanisms of the
      anti-erosive effect need to be explored in the future.

PMID- 29449066
TI  - Characteristics of headache in relation to the manifestation of Susac syndrome.
AB  - Susac syndrome is characterized by a clinical triad of encephalopathy, branch
      retinal artery occlusion, and hearing loss. Due to the absence of the whole
      complex of the triad in the majority of cases at disease presentation, the
      syndrome often remains underdiagnosed and untreated. Headache is estimated to
      affect up to 80% of Susac syndrome patients, but the relevance of headache
      characteristics and profile is not yet clear. The proposed diagnostic criteria of
      the European Susac Consortium acknowledge headache as a possible brain
      manifestation if it is new, described as migrainous or oppressive, and precedes
      the other symptoms by not more than 6 months. Herein, a case series of different
      migraine-like headache associations attributed to Susac syndrome is presented and
      discussed in relevance with previously published literature. Our patients
      experienced different presentations of migraine-like headache related with Susac
      syndrome: exacerbation and chronification of headache just before the
      manifestation of the first symptoms of Susac syndrome, the manifestation of
      headache during the first episode of the syndrome, and an increasing frequency of
      headache during the course of the disease. The diagnosis of Susac syndrome in all
      three cases was confirmed by typical clinical symptoms and findings in retinal
      fluorescein angiography, audiometry, and brain magnetic resonance imaging, based
      on the diagnostic criteria of the European Susac Consortium. Based on the
      analysis of our presented cases, we conclude that headache attributed to Susac's
      syndrome is of migraine-like type but could be of different presentations in
      relation to the onset of the syndrome.

PMID- 29449068
TI  - Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and
      autoimmunity.
AB  - Chemokines are mostly known for their chemotactic properties, and less for their
      ability to direct the biological function of target cells, including T cells. The
      current review focuses on a key chemokine named CXCL10 and its role in directing
      the migratory propertied and biological function of CD4+ and CD8+ T cells in the
      context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor
      that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known
      ligands: CXCL9, CXCL10 and CXCL11. Different studies, including those coming form
      our laboratory, indicated that aside of attracting CD8+ and CD4+ effector T cells
      to tumor sites and sites of inflammation CXCL10 directs the polarization and
      potentiates the biological function of these cells. This makes CXCL10 a "key
      driver chemokine" and a valid target for therapy of autoimmune diseases such as
      Inflammatory Bowl's Disease, Multiple Sclerosis, Rheumatoid arthritis and others.
      As for cancer this motivated different groups, including our group to develop
      CXCL10 based therapies for cancer due to its ability to enhance T-dependent anti
      cancer immunity. The current review summarizes these findings and their potential
      translational implication.

PMID- 29449067
TI  - The journey of radiofrequency-assisted liver resection.

PMID- 29449069
TI  - Repercussions of the Great East Japan Earthquake tsunami on ellipsoidal
      Alexandrium cysts (Dinophyceae) in Ofunato Bay, Japan.
AB  - Shellfish aquaculture in Ofunato Bay, Northeast Japan, was seriously damaged by a
      tsunami generated by the Great East Japan Earthquake, March 11th, 2011,
      accompanied by paralytic shellfish poisoning (PSP) outbreaks caused by
      Alexandrium tamarense (Dinophyceae). To understand longer future trends of PSP,
      an investigation was made of the historical occurrence and causes of Alexandrium
      outbreaks after the tsunami. Vertical distributions of Alexandrium cysts in two
      sediment-cores from Ofunato Bay revealed that the sediments above ca. 25 cm were
      eroded, re-suspended and re-deposited, and they included unusually abundant
      Alexandrium cysts. This abundance of cysts was due to re-deposition of older
      sediments by the tsunami. The first Ofunato Bay PSP incident was in 1961 after
      the Chilean Earthquake tsunami and was probably caused by similar unusual blooms
      of Alexandrium germinated from older sediments as the Great East Japan tsunami,
      together with nutrient enrichment because of population increase at the start of
      shellfish aquaculture.

PMID- 29449070
TI  - Physiological effects of marine natural organic matter and metals in early life
      stages of the North Pacific native marine mussel Mytilus trossulus; a comparison
      with the invasive Mytilus galloprovincialis.
AB  - The role of seawater NOM in reducing metal toxicity for marine organisms is not
      well understood. We investigated the effects of five different marine NOMs (two
      autochthonous, one allochthonous, two of mixed origin, at 8 mg C/L), three metals
      (6 MUg Cu/L; 20 MUg Pb/L; 25 MUg Zn/L), and combinations between them, to early
      life stages of Mytilus trossulus (a North Pacific native) in 48-h tests.
      Endpoints were whole body Ca2++Mg2+-ATPase activity, carbonic anhydrase (CA)
      activity and lipid peroxidation. Comparisons were made with previously reported
      tests (identical conditions) on the invasive M. galloprovincialis. Unexposed M.
      trossulus had lower Ca2++Mg2+-ATPase but similar baseline CA activity and lipid
      peroxidation to unexposed M. galloprovincialis. NOMs alone induced increased
      enzyme activities, and increased lipid peroxidation, but the latter did not occur
      with NOMs of mixed origin in M. trossulus. There was no clear difference in the
      sensitivity to various NOMs between species. In M. trossulus, all three metals by
      themselves caused increases in lipid peroxidation, as did many metal-NOM
      combinations. The origin of the NOMs influenced the nature of the responses to
      NOM-metal combinations in both species, but no clear relationship to NOM
      chemistry was apparent. Overall, M. trossulus was more sensitive to metals and
      NOM-metal combinations, with a greater number of significant responses (27 versus
      22 treatment endpoints, out of a total of 72) and a greater proportion of
      negative effects (81% versus 50%) than in M. galloprovincialis. Therefore, marine
      NOMs by themselves, as well as metals by themselves and NOM-metal combinations,
      can induce both positive and negative physiological responses. Lipid peroxidation
      appears to be a particularly common negative response. In future studies, NOM
      quality and mussel species should be considered since native M. trossulus and
      invasive M. galloprovincialis exhibited markedly different responses after
      exposure to the same environmental conditions.

PMID- 29449071
TI  - Do the morphological and functional traits of free-living marine nematodes mirror
      taxonomical diversity?
AB  - The taxonomical structure and diversity of nematode assemblages are the main
      attributes analyzed in ecology, but nematode adaptations to their habitats are
      still understudied. Accordingly, a survey on some known and other newly proposed
      morpho-functional traits was carried out in order to: determine if the morpho
      functional diversity of nematodes mirrors their taxonomical diversity; and assess
      potential nematode adaptations to sediment type and hydrodynamic stress. Morpho
      functional traits were investigated both singularly and together and showed
      significant differences related to these environmental factors. The greatest
      taxonomical and morpho-functional diversity was found in medium-coarse sand (M
      CS) and at an intermedium energy level (IEL). The M-CS and IEL were probably
      richer in micro-habitats and subject to a low selective pressure, hosting
      nematodes with a wide range of adaptations. The mirroring of morpho-functional
      diversity with taxonomical diversity is crucial for the future growth of the use
      of nematodes in biomonitoring. This is because the study of their morpho
      functional traits could reduce the level of work involved and the costs of any
      analyses.

PMID- 29449072
TI  - MERRF Classification: Implications for Diagnosis and Clinical Trials.
AB  - BACKGROUND: Given the etiologic heterogeneity of disease classification using
      clinical phenomenology, we employed contemporary criteria to classify variants
      associated with myoclonic epilepsy with ragged-red fibers (MERRF) syndrome and to
      assess the strength of evidence of gene-disease associations. Standardized
      approaches are used to clarify the definition of MERRF, which is essential for
      patient diagnosis, patient classification, and clinical trial design. METHODS:
      Systematic literature and database search with application of standardized
      assessment of gene-disease relationships using modified Smith criteria and of
      variants reported to be associated with MERRF using modified Yarham criteria.
      RESULTS: Review of available evidence supports a gene-disease association for two
      MT-tRNAs and for POLG. Using modified Smith criteria, definitive evidence of a
      MERRF gene-disease association is identified for MT-TK. Strong gene-disease
      evidence is present for MT-TL1 and POLG. Functional assays that directly
      associate variants with oxidative phosphorylation impairment were critical to
      mtDNA variant classification. In silico analysis was of limited utility to the
      assessment of individual MT-tRNA variants. With the use of contemporary
      classification criteria, several mtDNA variants previously reported as pathogenic
      or possibly pathogenic are reclassified as neutral variants. CONCLUSIONS: MERRF
      is primarily an MT-TK disease, with pathogenic variants in this gene accounting
      for ~90% of MERRF patients. Although MERRF is phenotypically and genotypically
      heterogeneous, myoclonic epilepsy is the clinical feature that distinguishes
      MERRF from other categories of mitochondrial disorders. Given its low frequency
      in mitochondrial disorders, myoclonic epilepsy is not explained simply by an
      impairment of cellular energetics. Although MERRF phenocopies can occur in other
      genes, additional data are needed to establish a MERRF disease-gene association.
      This approach to MERRF emphasizes standardized classification rather than
      clinical phenomenology, thus improving patient diagnosis and clinical trial
      design.

PMID- 29449073
TI  - Healthy minds 0-100 years: Optimising the use of European brain imaging cohorts
      ("Lifebrain").
AB  - The main objective of "Lifebrain" is to identify the determinants of brain,
      cognitive and mental (BCM) health at different stages of life. By integrating,
      harmonising and enriching major European neuroimaging studies across the life
      span, we will merge fine-grained BCM health measures of more than 5000
      individuals. Longitudinal brain imaging, genetic and health data are available
      for a major part, as well as cognitive and mental health measures for the broader
      cohorts, exceeding 27,000 examinations in total. By linking these data to other
      databases and biobanks, including birth registries, national and regional
      archives, and by enriching them with a new online data collection and novel
      measures, we will address the risk factors and protective factors of BCM health.
      We will identify pathways through which risk and protective factors work and
      their moderators. Exploiting existing European infrastructures and initiatives,
      we hope to make major conceptual, methodological and analytical contributions
      towards large integrative cohorts and their efficient exploitation. We will thus
      provide novel information on BCM health maintenance, as well as the onset and
      course of BCM disorders. This will lay a foundation for earlier diagnosis of
      brain disorders, aberrant development and decline of BCM health, and translate
      into future preventive and therapeutic strategies. Aiming to improve clinical
      practice and public health we will work with stakeholders and health authorities,
      and thus provide the evidence base for prevention and intervention.

PMID- 29449074
TI  - Onychomycosis due to dermatophytes species in Iran: Prevalence rates, causative
      agents, predisposing factors and diagnosis based on microscopic morphometric
      findings.
AB  - OBJECTIVE: Onychomycosis (OM) or fungal nail infection is one of the most common
      fungal infections, which is increasingly prevalent. OM is caused by dermatophytes
      spp, yeasts and non-dermatophyte moulds (NDMs). The purpose of this study was to
      identify and determine the prevalence rates, predisposing factors and causative
      agents of OM using clinical symptoms and microscopic morphometric findings.
      MATERIALS AND METHODS: In the present study, 180 patients suspected of OM were
      evaluated by direct microscopy using KOH 20%, culturing in Mycosel and Sabouraud
      dextrose agar media and Olysia software for identifying the causative fungi of
      OM. RESULTS: From 180 referred patients, 118 (65.56%) had OM, of whom 79 (66.94%)
      were positive for infection with dermatophytes spp. Of the 79 cases, the
      commonest age group was 61-70 years (21%) with males being 46 (58.23%) and
      females being 33 (41.77%). Both the fingernail and toenail infections were most
      prevalent in male patients. Sex, diabetes and age above 60 years were significant
      predisposing factors for OM development. DLSO was observed as the only clinical
      pattern of OM and T. rubrum was the commonest dermatophyte isolate (49.34%).
      CONCLUSION: This study showed that T. rubrum was the most common dermatophyte
      agent of OM in Iran.

PMID- 29449076
TI  - Editorial Overview: Growth and development.

PMID- 29449075
TI  - Cardiac transplantation in children with Down syndrome, Turner syndrome, and
      other chromosomal anomalies: A multi-institutional outcomes analysis.
AB  - BACKGROUND: The purpose of this study was to describe the prevalence,
      characteristics, and outcomes in pediatric patients with chromosomal anomalies
      (CA) undergoing orthotopic heart transplantation (OHT). METHODS: A query of the
      database of the Pediatric Health Information System, a large administrative and
      billing database of 43 tertiary children's hospitals, was performed for the Years
      2004 to 2016. Pediatric patients who received OHT were analyzed based on presence
      and type of CA. CA analyzed included: Down syndrome (DS); Turner syndrome
      (TS)/gonadal dysgenesis; conditions due to anomaly of unspecified chromosome;
      autosomal deletion; microdeletion; and autosomal anomaly. Healthcare-associated
      charge analysis during hospitalization for OHT and survival after OHT were
      assessed. RESULTS: A total of 3,080 hospitalizations were identified in which
      OHTs were performed. Of these OHTs, 64 (2.1%) were performed in patients with a
      concomitant diagnosis of CA. The presence of CA did not confer a higher risk of
      in-hospital mortality after OHT (odds ratio 1.2 [0.5 to 3.2], p = 0.651).
      Differences in in-hospital mortality between different types of CA, including DS
      and TS, did not reach statistical significance. Survival at 1-year post-OHT was
      similar in patients with CA compared to those without CA (p = 0.248). Length of
      stay after OHT was longer in patients with CA: 76 (interquartile range [IQR] 76
      to 142 days vs 49 [IQR 21 to 98] days) (p < 0.001), respectively. Overall
      adjusted hospital charges were significantly higher in the CA group: $1.2 million
      (IQR $740,000 to $2.2 million) vs $792,000 (IQR $425,000 to $1.5 million] (p <
      0.001), respectively. CONCLUSIONS: CA is present in ~2% of pediatric patients
      undergoing OHT. The presence of CA was not associated with increased mortality in
      pediatric patients undergoing OHT. Limitations of this study include the small
      number of patients available for analysis and a likely highly selective cohort of
      patients with CA.

PMID- 29449077
TI  - Not All Extracorporeal Shock Wave Therapies Are Equal: A Comment on Ulusoy et al.
      J Foot Ankle Surg 2017;56:762-767.

PMID- 29449078
TI  - [Cacogeusia and ingestion of pine nuts].

PMID- 29449079
TI  - Cost-Effectiveness of Ivabradine in the Treatment of Chronic Heart Failure.
AB  - BACKGROUND: In the Systolic Heart failure treatment with the If inhibitor Trial
      (SHIFT) randomised placebo-controlled trial, ivabradine was shown to reduce
      hospital admissions for worsening heart failure (HF) and deaths due to HF in
      patients with symptomatic systolic HF and an elevated resting heart rate (HR).
      This analysis evaluates the cost effectiveness of adding ivabradine to optimal
      standard HF treatment in patients with a HR>=77 bpm. METHODS: A Markov model was
      developed to assess the impact of ivabradine on mean survival and quality of life
      over a patient's lifetime (10 years). The hospitalisation and death rates were
      calculated using patient-level data from SHIFT. The reduction in quality of life
      due to HF hospitalisations was estimated directly from EQ-5D data collected in
      SHIFT. Australian costs were applied to the resource use from SHIFT. RESULTS: The
      modelled mean increase in survival with ivabradine was 0.115 years. The mean
      increase in quality-adjusted survival was 0.108 years. The average cost of
      ivabradine was A$2957 and the cost savings associated with a reduction in HF
      hospitalisations was A$1344. The cost per quality adjusted life year gained
      (QALYG) was A$14,905. The conservative approach to the modelled evaluation, as
      well as results of the sensitivity analysis, demonstrates that ivabradine is
      likely to be cost-effective in this indication. CONCLUSIONS: The conservative
      approach to the modelled evaluation, as well as results of the sensitivity
      analysis, demonstrates that ivabradine is a cost-effective treatment in the
      Australian setting for HF patients with a HR>=77 bpm on optimal standard therapy
      with a cost per QALYG similar or lower than that for other publicly funded
      treatments.

PMID- 29449080
TI  - Influence of exercise modality on cardiac parasympathetic and sympathetic indices
      during post-exercise recovery.
AB  - OBJECTIVES: This study investigated indirect measures of post-exercise
      parasympathetic reactivation (using heart-rate-variability, HRV) and sympathetic
      withdrawal (using systolic-time-intervals, STI) following upper- and lower-body
      exercise. DESIGN: Randomized, counter-balanced, crossover. METHODS: 13 males (age
      26.4+/-4.7years) performed maximal arm-cranking (MAX-ARM) and leg-cycling (MAX
      LEG). Subsequently, participants undertook separate 8-min bouts of submaximal HR
      matched exercise of each mode (ARM and LEG). HRV (including natural-logarithm of
      root-mean-square-of-successive-differences, Ln-RMSSD) and STI (including pre
      ejection-period, PEP) were assessed throughout 10-min seated recovery. RESULTS:
      Peak-HR was higher (p=0.001) during MAX-LEG (182+/-7beatsmin-1) compared with MAX
      ARM (171+/-12beatsmin-1), while HR (p<0.001) and Ln-RMSSD (p=0.010) recovered
      more rapidly following MAX-ARM. PEP recovery was similar between maximal bouts
      (p=0.106). HR during submaximal exercise was 146+/-7 (LEG) and 144+/-8beatsmin-1
      (LEG) (p=0.139). Recovery of HR and Ln-RMSSD was also similar between submaximal
      modalities, remaining below baseline throughout recovery (p<0.001). PEP was
      similar during submaximal exercise (LEG 70+/-6ms; ARM 72+/-9ms; p=0.471) although
      recovery was slower following ARM (p=0.021), with differences apparent from 1- to
      10-min recovery (p<=0.036). By 10-min post-exercise, PEP recovered to baseline
      (132+/-21ms) following LEG (130+/-21ms; p=0.143), but not ARM (121+/-17ms;
      p=0.001). CONCLUSIONS: Compared with submaximal lower-body exercise, HR-matched
      upper-body exercise elicited a similar recovery of HR and HRV indices of
      parasympathetic reactivation, but delayed recovery of PEP (reflecting sympathetic
      withdrawal). Exercise modality appears to influence post-exercise parasympathetic
      reactivation and sympathetic withdrawal in an intensity-dependent manner. These
      results highlight the need for test standardization and may be relevant to multi
      discipline athletes and in clinical applications with varying modes of exercise
      testing.

PMID- 29449081
TI  - Urinary concentrations of benzophenone-type ultra violet light filters and
      reproductive parameters in young men.
AB  - BACKGROUND: Benzophenone (BP)-type ultraviolet (UV) light filters are chemicals
      frequently added to personal care products, insect repellents, sunscreens, and
      beverage and food packaging to diminish the harmful effects of UV sunlight on
      human skin or foodstuffs. BP-type UV filters have shown negative effects on male
      reproduction function in in vitro and animal models, but human epidemiologic
      studies are limited. The goal of this study was to examine associations between
      urinary concentrations of BP-type UV filters and semen quality and reproductive
      hormone levels. METHODS: This is a cross-sectional study with 215 young
      university students (18-23 years old) recruited between 2010 and 2011 in Southern
      Spain (Murcia Region). All men provided a urine, blood and semen sample on a
      single day. Urinary concentrations of 2,4-dihydroxybenzophenone (BP-1); 2,2',4,4'
      tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2'
      dihydroxy-4-methoxybenzophenone (BP-8) and 4-hydroxybenzophenone (4OH-BP) were
      measured by dispersive liquid-liquid microextraction and ultra-high performance
      liquid chromatography with tandem mass spectrometry detection. Semen quality was
      evaluated by measuring volume, sperm counts, motility and morphology. Serum
      samples were analyzed for reproductive hormones, including follicle-stimulating
      hormone (FSH), luteinizing hormone (LH), testosterone (T), inhibin B and
      estradiol (E2). Associations between urinary concentrations of BP-type UV filters
      and semen quality parameters and reproductive hormone levels were examined using
      linear regression, adjusting for potential confounders. RESULTS: Ninety-seven
      percent of the men had detectable urinary concentrations of at least one of the
      five BP-type UV filters quantified. After adjustment for important covariates
      (body mass index, smoking status and time of blood sample collection), there was
      a significant positive association between urinary BP-1 and BP-3 concentrations
      and serum FSH levels (beta = 0.08, 95%CI: 0.009; 0.15 and beta = 0.04, 95%CI:
      0.0002; 0.08, respectively). Urinary BP-1 concentration was also significantly
      positively associated with T/E2 (beta = 0.04, 95%CI: 0.002; 0.07) and negatively
      with inhibin b/FSH (beta = -0.11, 95%CI: -0.21; -0.006) ratio. No significant
      associations were found between other urinary BP-type UV filters and other
      reproductive hormone levels or between any semen parameters and any of the
      urinary BP-type UV filters quantified. CONCLUSIONS: Our results suggest that, in
      young men, urinary BP-type UV filters may be associated with a modest alteration
      of some reproductive hormones, but the effects we report on reproductive function
      are likely to be small, and of unclear clinical significance. Further research is
      needed to replicate these findings in other male populations.

PMID- 29449082
TI  - Multiple sclerosis or "inflammatory CADASIL?": Case Report and review of the
      literature.
AB  - BACKGROUND: Multiple sclerosis (MS) and CADASIL presenting together is
      exceedingly rare. As more cases of "inflammatory" CADASIL emerge, diagnostic
      challenges for clinicians increase. We report an individual with MS and CADASIL
      presenting with cognitive decline at age 25. She presented with gadolinium
      enhancing lesions on MRI and inflammatory cerebrospinal fluid raising the
      question of whether these patients should be given a diagnosis of "inflammatory
      CADASIL" or both MS and CADASIL. METHODS: A literature review was conducted on
      reports of inflammatory CADASIL or MS and CADASIL, clinical presentations
      including spinal cord lesions and CSF inflammatory markers. RESULTS: Nine cases
      in the literature of individuals with CADASIL and inflammatory presentations were
      found with treatment varying from intravenous steroids to MS immunomodulatory
      therapy. CONCLUSIONS: If individuals with CADASIL present with immune mediated
      inflammatory components they may benefit from immunomodulatory therapy. This is
      discussed with a review of the inflammatory CADASIL/MS cases in the literature
      and report of a case.

PMID- 29449083
TI  - Three-dimensional scapular dyskinesis in hook-plated acromioclavicular
      dislocation including hook motion.
AB  - BACKGROUND: The purpose of this study is to analyze the 3-dimensional scapular
      dyskinesis and the kinematics of a hook plate relative to the acromion after hook
      plated acromioclavicular dislocation in vivo. Reported complications of
      acromioclavicular reduction using a hook plate include subacromial erosion and
      impingement. However, there are few reports of the 3-dimensional kinematics of
      the hook and scapula after the aforementioned surgical procedure. METHODS: We
      studied 15 cases of acromioclavicular dislocation treated with a hook plate and
      15 contralateral normal shoulders using computed tomography in the neutral and
      full forward flexion positions. Three-dimensional motion of the scapula relative
      to the thorax during arm elevation was analyzed using a computer simulation
      program. We also measured the distance from the tip of the hook plate to the
      greater tuberosity, as well as the angular motion of the plate tip in the
      subacromial space. RESULTS: Decreased posterior tilting (22 degrees  +/- 10
      degrees  vs 31 degrees  +/- 8 degrees ) in the sagittal plane and increased
      external rotation (19 degrees  +/- 9 degrees  vs 7 degrees  +/- 5 degrees ) in
      the axial plane were evident in the affected shoulders. The mean values of
      translation of the hook plate and angular motion against the acromion were 4.0 +/
      1.6 mm and 15 degrees  +/- 8 degrees , respectively. The minimum value of the
      distance from the hook plate to the humeral head tuberosity was 6.9 mm during arm
      elevation. CONCLUSIONS: Acromioclavicular reduction using a hook plate may cause
      scapular dyskinesis. Translational and angular motion of the hook plate against
      the acromion could lead to subacromial erosion. However, the hook does not seem
      to impinge directly on the humeral head.

PMID- 29449084
TI  - Paralabral cysts of the shoulder treated with isolated labral repair: effect on
      pain and radiologic findings.
AB  - BACKGROUND: Paralabral cysts emanating from posterosuperior labral tears may
      compress the suprascapular nerve and induce neuropathy. This study prospectively
      assessed patients with labral tears and symptomatic paralabral cysts treated with
      isolated labral repair. Pain relief, time to cyst resolution, reversibility of
      muscular edema, atrophy, fatty infiltration, and bone erosion were evaluated.
      METHODS: Forty-seven patients with symptomatic posterosuperior paralabral cysts
      were treated with isolated labral repair. Magnetic resonance imaging (MRI) was
      repeated 6 and 12 weeks postoperatively or until cyst resolution. In a subgroup
      of 15 patients, MRI was performed the day before the operation, the first
      postoperative day, and at 2 weeks. RESULTS: Median cyst size was 6.8 cm3 (range,
      2.1-88.9; standard deviation [SD], 18.3 cm3). Preoperatively, 20 patients (43%)
      presented clinical muscle atrophy and radiologic edema on MRI, 8 had fatty
      infiltration, and 3 presented bony scapular erosion caused by cyst compression.
      Median time to cyst resolution and regression of muscular edema was 11 weeks
      (range, 3-20; SD, 8.8 weeks) and 14 weeks (range, 3-52; SD 10.6 weeks),
      respectively. Preoperative fatty infiltration grade I and II of the supraspinatus
      and infraspinatus muscles was reduced in two patients. Bony erosions remodeled
      after cyst resolution. Mean pain ratings (1-10 scale) improved from 7.7 (SD, 1.8)
      to 1.3 (SD, 1.3; 95% confidence interval of difference, 5.5-6.8; P < .001).
      CONCLUSION: Labral repair leads to significant pain relief with cyst resolution
      within 2 to 3 months in most patients. Secondary muscle pathology (ie, edema,
      atrophy and fatty infiltration) may be partially or completely reversed. Bony
      erosion caused by cyst compression may be remodeled after cyst resolution.

PMID- 29449085
TI  - The simultaneous isolation of multiple high and low frequent T-cell populations
      from donor peripheral blood mononuclear cells using the major histocompatibility
      complex I-Streptamer isolation technology.
AB  - BACKGROUND: Adoptive transfer of donor-derived T cells can be applied to improve
      immune reconstitution in immune-compromised patients after allogeneic stem cell
      transplantation. The separation of beneficial T cells from potentially harmful T
      cells can be achieved by using the major histocompatibility complex (MHC) I
      Streptamer isolation technology, which has proven its feasibility for the fast
      and pure isolation of T-cell populations with a single specificity. We have
      analyzed the feasibility of the simultaneous isolation of multiple antigen
      specific T-cell populations in one procedure by combining different MHC I
      Streptamers. METHODS: First, the effect of combining different amounts of MHC I
      Streptamers used in the isolation procedure on the isolation efficacy of target
      antigen-specific T cells and on the number of off-target co-isolated
      contaminating cells was assessed. The feasibility of this approach was
      demonstrated in large-scale validation procedures targeting both high and low
      frequent T-cell populations using the Good Manufacturing Practice (GMP)-compliant
      CliniMACS Plus device. RESULTS: T-cell products targeting up to 24 different T
      cell populations could be isolated in one, simultaneous MHC I-Streptamer
      procedure, by adjusting the amount of MHC I- Streptamers per target antigen
      specific T-cell population. Concurrently, the co-isolation of potentially harmful
      contaminating T cells remained below our safety limit. This technology allows the
      reproducible isolation of high and low frequent T-cell populations. However, the
      expected therapeutic relevance of direct clinical application without in vitro
      expansion of these low frequent T-cell populations is questionable. DISCUSSION:
      This study provides a feasible, fast and safe method for the generation of highly
      personalized MHC I-Streptamer isolated T-cell products for adoptive
      immunotherapy.

PMID- 29449086
TI  - Progress in the use of dental pulp stem cells in regenerative medicine.
AB  - The field of tissue engineering is emerging as a multidisciplinary area with
      promising potential for regenerating new tissues and organs. This approach
      requires the involvement of three essential components: stem cells, scaffolds and
      growth factors. To date, dental pulp stem cells have received special attention
      because they represent a readily accessible source of stem cells. Their high
      plasticity and multipotential capacity to differentiate into a large array of
      tissues can be explained by its neural crest origin, which supports applications
      beyond the scope of oral tissues. Many isolation, culture and cryopreservation
      protocols have been proposed that are known to affect cell phenotype,
      proliferation rate and differentiation capacity. The clinical applications of
      therapies based on dental pulp stem cells demand the development of new
      biomaterials suitable for regenerative purposes that can act as scaffolds to
      handle, carry and implant stem cells into patients. Currently, the development of
      xeno-free culture media is emerging as a means of standardization to improve safe
      and reproducibility. The present review aims to describe the current knowledge of
      dental pulp stem cells, considering in depth the key aspects related to the
      characterization, establishment, maintenance and cryopreservation of primary
      cultures and their involvement in the multilineage differentiation potential. The
      main clinical applications for these stem cells and their combination with
      several biomaterials is also covered.

PMID- 29449087
TI  - Two-dimensional correlation spectroscopic studies on coordination between organic
      ligands and Ni2+ ions.
AB  - 3A2g->3T1g(P) transition band of Ni2+ is used to probe the coordination of Ni2+.
      Two-dimensional asynchronous spectra (2DCOS) are generated using the Double
      Asynchronous Orthogonal Sample Design (DAOSD), Asynchronous Spectrum with
      Auxiliary Peaks (ASAP) and Two-Trace Two-Dimensional (2T2D) approaches. Cross
      peaks relevant to the 3A2g->3T1g(P) transition band of Ni2+ are utilized to probe
      coordination between Ni2+ and various ligands. We studied the spectral behavior
      of the 3A2g->3T1g(P) transition band when Ni2+ is coordinated with
      ethylenediaminetetraacetic acid disodium salt (EDTA). The pattern of cross peaks
      in 2D asynchronous spectrum demonstrates that coordination brings about
      significant blue shift of the band. In addition, the absorptivity of the band
      increases remarkably. The interaction between Ni2+ and galactitol is also
      investigated. Although no clearly observable change is found on the 3A2g->3T1g(P)
      transition band when galactitol is introduced, the appearance of cross peak in 2D
      asynchronous spectrum demonstrates that coordination indeed occurs between Ni2+
      and galactitol. Furthermore, the pattern of cross peak indicates that peak
      position, bandwidth and absorptivity of the 3A2g->3T1g(P) transition band of
      Ni(galactitol)x2+ is considerably different from those of Ni(H2O)62+. Thus, 2DCOS
      is helpful to reveal subtle spectral variation, which might be helpful in
      shedding light on the physical-chemical nature of coordination.

PMID- 29449088
TI  - Temperature Modulates Tissue-Specification Program to Control Fruit Dehiscence in
      Brassicaceae.
AB  - Plants respond to diurnal and seasonal changes in temperature by reprogramming
      vital developmental pathways. Understanding the molecular mechanisms that define
      environmental modulation of plant growth and reproduction is critical in the
      context of climate change that threatens crop yield worldwide. Here, we report
      that elevated temperature accelerates fruit dehiscence in members of the
      Brassicaceae family including the model plant Arabidopsis thaliana and important
      crop species. Arabidopsis fruit development is controlled by a network of
      interacting regulatory genes. Among them, the INDEHISCENT (IND) gene is a key
      regulator of the valve-margin tissue that mediates fruit opening, hence
      facilitating fruit dehiscence. We demonstrated that the valve-margin development
      is accelerated at higher temperature and that IND is targeted for thermosensory
      control. Our results reveal that IND upregulation is facilitated via temperature
      induced chromatin dynamics leading to accelerated valve-margin specification and
      dispersal of the seed. Specifically, we show that temperature-induced changes in
      IND expression are associated with thermosensory H2A.Z nucleosome dynamics. These
      findings establish a molecular framework connecting tissue identity with thermal
      sensing and set out directions for the production of temperature-resilient crops.

PMID- 29449089
TI  - Characterization of the lncRNA transcriptome in mESC-derived motor neurons:
      Implications for FUS-ALS.
AB  - Long non-coding RNAs (lncRNAs) are currently recognized as crucial players in
      nervous system development, function and pathology. In Amyotrophic Lateral
      Sclerosis (ALS), identification of causative mutations in FUS and TDP-43 or
      hexanucleotide repeat expansion in C9ORF72 point to the essential role of
      aberrant RNA metabolism in neurodegeneration. In this study, by taking advantage
      of an in vitro differentiation system generating mouse motor neurons (MNs) from
      embryonic stem cells, we identified and characterized the long non-coding
      transcriptome of MNs. Moreover, by using mutant mouse MNs carrying the equivalent
      of one of the most severe ALS-associated FUS alleles (P517L), we identified
      lncRNAs affected by this mutation. Comparative analysis with human MNs derived in
      vitro from induced pluripotent stem cells indicated that candidate lncRNAs are
      conserved between mouse and human. Our work provides a global view of the long
      non-coding transcriptome of MN, as a prerequisite toward the comprehension of the
      still poorly characterized non-coding side of MN physiopathology.

PMID- 29449090
TI  - Clinical and Molecular Characteristics and Burden of Kidney Cancer Among
      Hispanics and Native Americans: Steps Toward Precision Medicine.
AB  - Cancer disparities in Native Americans (NAs) and Hispanic Americans (HAs) vary
      significantly in terms of cancer incidence and mortality rates across geographic
      regions. This review reports that kidney and renal pelvis cancers are unevenly
      affecting HAs and NAs compared to European Americans of non-Hispanic origin, and
      that currently there is significant need for improved data and reporting to be
      able to advance toward genomic-based precision medicine for the assessment of
      such cancers in these medically underserved populations. More specifically, in
      states along the US-Mexico border, HAs and NAs have higher kidney cancer
      incidence rates as well as a higher prevalence of kidney cancer risk factors,
      including obesity and chronic kidney disease. They are also more likely to
      receive suboptimal care compared to European Americans. Furthermore, they are
      underrepresented in epidemiologic, clinical, and molecular genomic studies of
      kidney cancer. Therefore, we maintain that progress in precision medicine for
      kidney cancer care requires an understanding of various factors among HAs and
      NAs, including the real kidney cancer burden, variations in clinical care, issues
      related to access to care, and specific clinical and molecular characteristics.

PMID- 29449091
TI  - Adjuvant Therapies in Nonmetastatic Renal-Cell Carcinoma: A Review of the
      Literature.
AB  - To conduct a review of literature on adjuvant therapy in nonmetastatic renal-cell
      carcinoma (nmRCC) treated with nephrectomy and to describe the efficacy of
      adjuvant agents on cancer control outcomes. A review of the literature was
      performed in January 2018 to identify all studies evaluating adjuvant therapy in
      patients with nmRCC treated with nephrectomy using PubMed, Embase, Medline, and
      Cochrane Library databases. The following keywords were used: adjuvant therapy,
      renal-cell carcinoma, nonmetastatic, targeted molecular therapy, kidney cancer.
      The ClinicalTrials.gov website was queried to identify ongoing trials.
      Traditional adjuvant therapy agents consisted of interferon alpha, interleukin 2,
      autologous tumor cell vaccines, and monoclonal antibodies. None provided survival
      benefit. Three contemporary studies (S-TRAC, ASSURE, and PROTECT) using targeted
      therapy compared sunitinib to placebo (S-TRAC), sunitinib or sorafenib to placebo
      (ASSURE), and pazopanib to placebo (PROTECT), with controversial results. In
      contrast to ASSURE and PROTECT, S-TRAC demonstrated improved disease-free
      survival. Several trials that use checkpoint immunotherapy agents or vascular
      endothelial growth factor receptor tyrosine kinase inhibitors are ongoing. Many
      traditional therapies have shown no success as adjuvant therapy for nmRCC after
      nephrectomy. Targeted adjuvant therapy for nmRCC after nephrectomy showed
      controversial results, and its routine use is not currently endorsed.

PMID- 29449092
TI  - Efficacy of narrow-band imaging for detecting intestinal metaplasia in adult
      patients with symptoms of dyspepsia.
AB  - INTRODUCTION AND OBJECTIVE: Atrophy and intestinal metaplasia are early
      phenotypic markers in gastric carcinogenesis. White light endoscopy does not
      allow direct biopsy of intestinal metaplasia due to a lack of contrast of the
      mucosa. Narrow-band imaging is known to enhance the visibility of intestinal
      metaplasia, to reduce sampling error, and to increase the diagnostic yield of
      endoscopy for intestinal metaplasia in Asian patients. The aim of our study was
      to validate the diagnostic performance of narrow-band imaging using 1.5*
      electronic zoom endoscopy (with no high magnification) to diagnose intestinal
      metaplasia in Mexican patients. MATERIALS AND METHODS: A retrospective cohort
      study was conducted on consecutive patients with dyspeptic symptoms at a private
      endoscopy center within the time frame of January 2015 to December 2016. RESULTS:
      A total of 338 patients (63+/-8.4 years of age, 40% women) were enrolled. The
      prevalence of H. pylori infection was 10.9% and the incidence of intestinal
      metaplasia in the gastric antrum and corpus was 23.9 and 5.9%, respectively.
      Among the patients with intestinal metaplasia, 65.3% had the incomplete type,
      42.7% had multifocal disease, and one third had extension to the gastric corpus.
      Two patients had low-grade dysplasia. The sensitivity of white light endoscopy
      was 71.2%, with a false negative rate of 9.9%. The sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy of narrow-band
      imaging (with a positive light blue crest) were 85, 98, 86.8, 97.7, and 87.2%,
      respectively. CONCLUSION: The prevalence of H. pylori infection and intestinal
      metaplasia in dyspeptic Mexican patients was not high. Through the assessment of
      the microsurface structure and light blue crest sign, non-optical zoom narrow
      band imaging had high predictive values for detecting intestinal metaplasia in
      patients from a general Western setting.

PMID- 29449093
TI  - Fecal microbiota transplantation for severe complicated C. difficile colitis in a
      patient with acquired immunodeficiency syndrome.

PMID- 29449094
TI  - Safety and efficacy of small bowel polypectomy using a balloon-assisted
      enteroscope in pediatric patients with Peutz-Jeghers syndrome.
AB  - INTRODUCTION AND AIMS: Peutz-Jeghers syndrome is an autosomal dominant inherited
      pathology characterized by gastrointestinal hamartomatous polyps, predominantly
      in the small bowel, and pigmented mucocutaneous lesions. Guidelines suggest
      polypectomy with a balloon-assisted enteroscope when polyps are larger than 10mm.
      Complications in adults can be as high as 6.8%, but there is little information
      on pediatric populations. Our aim was to describe the safety and efficacy of
      polypectomy in a group of pediatric patients with Peutz-Jeghers syndrome using
      balloon-assisted enteroscopy. MATERIALS AND METHODS: A retrospective study was
      conducted at the Hospital de Especialidades del Centro Medico Nacional Siglo XXI
      on pediatric patients with Peutz-Jeghers syndrome that required balloon-assisted
      enteroscopy and polypectomy within the time frame of January 2010 and December
      2015. Patients that underwent polypectomy with a push enteroscope were excluded
      from the study. RESULTS: A total of 35 polypectomies were performed on 4 patients
      (female/male: 3/1). The mean age of the patients was 13.7 years (range:11-16).
      Twelve enteroscopies were carried out, 8 of which were anterograde. A single
      balloon enteroscope was used in 7 procedures and a double-balloon enteroscope in
      5. The mean size of the polyps was 1.6cm (range: 1-4cm). A major complication
      (acute pancreatitis) presented in only one case (8.3%). No other major
      complications associated with the procedures were observed. CONCLUSION: Balloon
      assisted enteroscopy with polypectomy in children is a safe and effective
      procedure, with complications similar to those reported in adults.

PMID- 29449096
TI  - Evaluating the Impact of Diabetes Self-Management Education Methods on Knowledge,
      Attitudes and Behaviours of Adult Patients With Type 2 Diabetes Mellitus.
AB  - OBJECTIVES: Diabetes self-management refers to all activities patients undertake
      to care for their illness, promote health and prevent the long- and short-term
      effects of diabetes. This study compared the effectiveness of 2 diabetes self
      management education methods by examining changes in glycated hemoglobin (A1C)
      levels and knowledge, attitudes and behaviours (KABs) after traditional group
      education (TE) or with diabetes conversation maps (CMs). The CMs group was
      postulated to show greater decrease in A1C levels and improved KABs scores
      compared to the TE group. METHODS: A sample of 21 eligible clients from Diabetes
      Care Guelph were randomly assigned into 2 groups: 10 receiving education through
      CMs and 11 through TE. Changes in knowledge and attitude were determined by using
      questionnaires and repeated-measures pretest and post-test design before and
      after the education sessions. Changes in A1C levels were determined by comparing
      values at baseline and at 3 months after receiving diabetes education. Two focus
      groups were conducted to obtain participants' perceptions of the education
      methods and self-reported KAB changes. RESULTS: Significant differences in
      knowledge and attitude score changes were observed from baseline/initial
      education and after 3 months. Both groups had significant decreases in A1C levels
      from baseline to 3 months afterward. Focus groups revealed themes common to both
      groups, such as benefits of early education, the need for multiple lifestyle
      behaviour changes and feelings about social support. CONCLUSIONS: CMs had a
      significant impact and are effective for group education. The changes observed
      may lead to improved diabetes self-management, thus reducing costly health
      complications related to poorly controlled diabetes.

PMID- 29449095
TI  - Relationships between bacteriospermia, DNA integrity, nuclear protamine
      alteration, sperm quality and ICSI outcome.
AB  - : The Aim of this study was to evaluate the effects of bacteriospermia on human
      sperm parameters, nuclear protamines, DNA integrity and ICSI outcome in patients
      enrolled for ICSI treatment. 84 unselected couples consulting in infertility and
      obstetrics clinic and enrolled for ICSI treatment were included in this study.
      The semen specimens were screened bacteriologically; semen and sperm parameters
      were also evaluated according to WHO guidelines. DNA integrity, protamines
      concentration and protamine deficiency were estimated by TUNEL assay, AU-PAGE and
      Chromomycin (CMA3) respectively. The results of this study revealed that 34.52%
      of studied semen samples were infected with bacteria. The isolated bacteria were
      identified as Staphylococcus aureus, Staph. epidermidis, Staph. haemolyticus,
      Escherichia coli, Enterococcus faecalis and Streptococcus agalactiae.
      Bacteriospermia had a significant (p < .010) negative effect on sperm parameters;
      concentration, motility, progressive motility and chromatin condensation.
      Moreover, high DNA fragmentation with low P1 and P2 concentrations were noticed
      in infected patients in comparison to non-infected patients but non-significant.
      Also, the fertilization rate decreased significantly (p < .05) with infected
      patients. IN CONCLUSION: bacteriospermia has significant negative effect on sperm
      quality and fertilization rate in patients who underwent ICSI treatment.

PMID- 29449097
TI  - 'The Unhealthy Other': How vaccine rejecting parents construct the vaccinating
      mainstream.
AB  - To address the phenomenon of vaccine hesitancy and rejection, researchers
      increasingly recognise the need to engage with the social context of parents'
      decision-making. This study examines how vaccine rejecting parents socially
      construct the vaccinating mainstream in opposition to themselves. We analyse
      qualitative data from interviews with parents in Adelaide, South Australia.
      Applying insights from Social Identity Theory (SIT), we show how these parents
      bolster their own sense of identity and self-belief by employing a discourse that
      casts vaccinators as an Unhealthy Other. We demonstrate how the parents identify
      vaccination as a marker of parental conformity to the 'toxic practices of mass
      industrial society', linking it to other ways in which membership of the
      consumerist mainstream requires individuals to 'neglect their health.' This is
      explored through themes of appearance, diet, (over) consumption of
      pharmaceuticals, inadequate parenting values and wilful or misguided ignorance.
      This construction of the Unhealthy Other elevates the self-concept of vaccine
      hesitant and rejecting parents, who see themselves as part of an enlightened, but
      constantly besieged, group of healthy and virtuous parents. It is common for the
      vaccinating mainstream to present vaccine hesitant and rejecting parents as a
      group subject to epistemic closure, groupthink, confirmation bias and over
      confidence in their own expertise. However, vaccine hesitant and rejecting
      parents also see mainstream society as a group-a much larger one-subject to the
      same problems. We suggest the need to mitigate the 'groupness' of vaccination and
      non-vaccination by extending the practice of vaccination to recognisable
      practitioners of holistic health.

PMID- 29449098
TI  - Quantification of human complement factor H binding to asexual malaria blood
      stages by an enzyme-linked immunosorbent assay.
AB  - The human complement system is the most effective defense mechanism of the human
      innate immune system. One major negative regulator of the alternative pathway in
      human blood is complement factor H (FH). It binds to autologous cells and thus,
      prevents complement attack against body-cells or tissues. Various pathogens are
      known to escape complement recognition by recruiting FH to provide protection
      against the host's immune system. This immune evasion mechanism was recently
      qualitatively reported for asexual malaria blood stages. To indirectly evaluate
      the stage-specific potential of FH-receptor proteins as vaccine candidates, we
      quantified the FH molecules bound to the surface of different malaria blood stage
      parasites by Western blot and a commercially available FH-ELISA, which was
      originally designed to measure the FH concentration in human serum. Host-cell
      free merozoites and intracellular mature schizont (here called segmenter) stages
      bind significantly more FH molecules than earlier parasite stages.

PMID- 29449099
TI  - Cost of goods sold and total cost of delivery for oral and parenteral vaccine
      packaging formats.
AB  - Despite limitations of glass packaging for vaccines, the industry has been slow
      to implement alternative formats. Polymer containers may address many of these
      limitations, such as breakage and delamination. However, the ability of polymer
      containers to achieve cost of goods sold (COGS) and total cost of delivery (TCOD)
      competitive with that of glass containers is unclear, especially for cost
      sensitive low- and lower-middle-income countries. COGS and TCOD models for oral
      and parenteral vaccine packaging formats were developed based on information from
      subject matter experts, published literature, and Kenya's comprehensive multiyear
      plan for immunization. Rotavirus and inactivated poliovirus vaccines (IPV) were
      used as representative examples of oral and parenteral vaccines, respectively.
      Packaging technologies evaluated included glass vials, blow-fill-seal (BFS)
      containers, preformed polymer containers, and compact prefilled auto-disable
      (CPAD) devices in both BFS and preformed formats. For oral vaccine packaging, BFS
      multi-monodose (MMD) ampoules were the least expensive format, with a COGS of
      $0.12 per dose. In comparison, oral single-dose glass vials had a COGS of $0.40.
      BFS MMD ampoules had the lowest TCOD of oral vaccine containers at $1.19 per dose
      delivered, and ten-dose glass vials had a TCOD of $1.61 per dose delivered. For
      parenteral vaccines, the lowest COGS was achieved with ten-dose glass vials at
      $0.22 per dose. In contrast, preformed CPAD devices had the highest COGS at $0.60
      per dose. Ten-dose glass vials achieved the lowest TCOD of the parenteral vaccine
      formats at $1.56 per dose delivered. Of the polymer containers for parenteral
      vaccines, BFS MMD ampoules achieved the lowest TCOD at $1.89 per dose delivered,
      whereas preformed CPAD devices remained the most expensive format, at $2.25 per
      dose delivered. Given their potential to address the limitations of glass and
      reduce COGS and TCOD, polymer containers deserve further consideration as
      alternative approaches for vaccine packaging.

PMID- 29449101
TI  - Evaluation of a convenient vaccination schedule against hepatitis B in HIV
      patients with undetectable HIV viral load.
AB  - Vaccination against hepatitis B virus (HBV) is recommended for all HIV-positive
      individuals but the standard schedule is not satisfactory. High or more doses
      have also been studied with variable results. We compared a vaccination schedule
      with a higher dose but fewer shots to the standard scheme (HBVaxPro 40 MUg versus
      Engerix 20 MUg at 0, 1, and 6 months). Of the 63 patients vaccinated with
      HBVaxPro 79%, 65% and 47% seroconverted at month 1, 12 and 24 after vaccination,
      respectively. A total of 137 patients received Engerix and showed lower response
      rates (68%, 53% and 38%, respectively). Anti-HBs titers in the Engerix group were
      also lower with a statistically significant difference. In patients younger than
      55 years HBVaxPro was 3 times more likely to provoke a response compared with
      Engerix (OR = 3, p = 0.006). In conclusion, HBVaxPro 40 MUg at 3 doses could be
      proposed as a more robust and acceptable alternative.

PMID- 29449100
TI  - Hepatitis A vaccination coverage among adolescents (13-17 years) in the United
      States, 2008-2016.
AB  - BACKGROUND: The hepatitis A (HepA) vaccine was recommended by the Advisory
      Committee on Immunization Practices (ACIP) incrementally from 1996 to 1999. In
      2006, HepA vaccine was recommended (1) universally for children aged 12-23
      months, (2) for persons who are at increased risk for infection, or (3) for any
      person wishing to obtain immunity. Catch-up vaccination can be considered.
      OBJECTIVE: To assess HepA vaccine coverage among adolescents and factors
      independently associated with vaccination administration in the US. METHODS: The
      2008-2016 National Immunization Survey-Teen was utilized to determine 1 and >=2
      dose HepA vaccination coverage among adolescents aged 13-17 years. Factors
      associated with HepA vaccine series initiation (1 dose) were determined by
      bivariate and multivariable analyses. Data were stratified by state groups based
      on ACIP recommendation: universal child vaccination recommended since 1999 (group
      1); child vaccination considered since 1999 (group 2); universal child
      vaccination recommendation since 2006 (group 3). RESULTS: In 2016, national
      vaccination coverage for 1 and >=2 doses of HepA vaccine among adolescents was
      73.9% and 64.4%, respectively. Nationally, a 40 percentage point increase in
      vaccination coverage occurred among adolescents born in 1995 compared to
      adolescents born in 2003. Nationally, the independent factors associated with
      increased vaccine initiation was race/ethnicity (Hispanic, American
      Indian/Alaskan Native, Asian), military payment source and provider
      recommendation for HepA vaccination (2008-2013). Living in a suburban or rural
      region, living in poverty (level <1.33-5.03), and absence of state daycare or
      school HepA requirement were common factors associated with decreased likelihood
      of vaccine initiation. CONCLUSIONS: Efforts to increase HepA vaccine coverage in
      adolescents in all regions of the country would strengthen population protection
      from hepatitis A virus (HAV).

PMID- 29449103
TI  - Calcitonin and Omega-3 Fatty Acids Exhibit Antagonistic and Non-Additive Effects
      in Experimental Diabetes.
AB  - Because optimising therapy for the management of diabetes mellitus remains
      challenging, the study investigated the effects of salmon calcitonin (Sct) and/or
      omega-3 fatty acids (N-3 - eicosapentaenoic acid and docosahexaenoic acid-3:2),
      compared to metformin, on selected biochemical parameters in male Wistar rats, in
      an experimental model of diabetes. Forty rats were used for this study. They were
      divided into eight groups of five rats each, which included: Normal control;
      Diabetic (D) control; D + N-3; D + low dose Sct (Sct. Lw); D + high dose Sct
      (Sct. Hi); D + N-3 + Sct.Lw; D + N-3 + Sct.Hi; and D + metformin. Diabetes was
      induced in overnight fasted rats by the administration of streptozotocin (65
      mg/kg b.w., i.p.), 15 min after the administration of nicotinamide (110 mg/kg
      b.w., i.p.). Nine days later, Sct was administered at 2.5 and 5.0 IU/kg b.w./day
      (i.m.), while N-3 and metformin were administered at 200 and 180 mg/kg b.w./day
      (p.o.) respectively, for four weeks. Sct, N-3, and metformin significantly
      reduced total cholesterol, LDL-C, cortisol, c-telopeptide of type 1 collagen, and
      collagen type 2 alpha-1. The combined administration of Sct and N-3 had more
      favorable effects on triglyceride and HDL-C than either monotherapy. Unlike
      metformin and Sct. Hi, N-3 significantly reduced alkaline phosphatase activity.
      Moreover, N-3 significantly suppressed the hypocalcaemic, hyperglycaemic, and
      insulin resistance provoking actions of Sct. Furthermore, N-3 contradicted the
      hepatic glycogen depletion and inhibition of nitric oxide synthesis brought about
      by Sct. In conclusion, N-3 demonstrated antagonistic and non-additive actions
      with Sct. Moreover, the effects of the combined administration of Sct and N-3
      were comparable to that of metformin; therefore, they might be considered as
      therapeutic alternatives in diabetes.

PMID- 29449102
TI  - Anterosuperior anchoring myringoplasty using cyanoacrylate glue can prevent
      packing gelfoam in the middle ear cavity.
AB  - OBJECTIVES: Although a number of methods have been attempted to improve securing
      the graft, packing gelfoam in the middle ear cavity cannot be avoided, which
      could obstruct the tympanic ostium of the Eustachian tube and affect inner ear
      function. Myringoplasty using tissue adhesive has gained traction because tissue
      adhesives can effectively stabilise the graft and act as scaffolding to improve
      the graft uptake. The aim of this prospective study was to explore myringoplasty
      using cyanoacrylate glue with no packing in the middle ear cavity for the repair
      of subtotal tympanic membrane (TM) perforations. METHODS: Between March 2014 and
      November 2015, 71 patients with subtotal TM perforations were randomly and
      prospectively divided into a glue group and a control group. Two securing
      techniques were performed using only cyanoacrylate glue or using only filling
      gelfoam in the middle ear cavity, respectively, during an anterosuperior
      anchoring myringoplasty operated by a single surgeon. RESULTS: At a 6-month
      follow-up, the graft uptake rate was 87% in the glue group and 89% in the control
      group. A significant hearing improvement was found in both groups postoperatively
      when compared to the preoperative values (P<0.05 for both). There was no
      significant difference in the graft uptake rate and hearing improvement between
      the 2 groups (P>0.05). Similar complications were found in each group.
      CONCLUSION: Cyanoacrylate glue is a helpful material for graft stabilisation and
      can substitute for filling gelfoam in the middle ear cavity during anterosuperior
      anchoring myringoplasty for subtotal TM perforation.

PMID- 29449104
TI  - Prefrontal direct current stimulation in hoarding disorder: A case report.

PMID- 29449105
TI  - Comparing cryptomarkets for drugs. A characterisation of sellers and buyers over
      time.
AB  - INTRODUCTION: Cryptomarkets operating on the darknet are a recent phenomenon that
      has gained importance only over the last couple of years (Barratt, 2012).
      However, they now constitute an evolving part of illicit drug markets. Although
      selling and buying a variety of psychoactive substances on the Internet has a
      long history, new technological developments enable systematic drug trading on
      the net.These technological innovations on the Internet allow users to proceed
      with (illicit) drug transactions with almost completely anonymous identities and
      locations. In this paper, we provide a systematic measurement analysis of
      structures and trends on the most popular anonymous drug marketplace, and discuss
      the role of cryptomarkets in drug distribution. METHODS: Data collection and
      analysis include a long-term measurement of the cryptomarket 'AlphaBay', the most
      popular platform during the survey period. By developing and applying a web
      scraping tool, market data was extracted from the marketplace on a daily basis
      during a period of twelve months between September 2015 and August 2016. The data
      was analysed by using business-intelligence software, which allows the linking of
      various data sets. We found 2188 unique vendors offering 11,925 drug items. The
      findings of our long-term monitoring and data analysis are compared over time and
      across marketplaces, offering a detailed understanding of the development of
      revenues generated, characterisation of countries of origin and destination, and
      distribution of vendors and customers over time. RESULTS: We provide a nuanced
      and highly detailed longitudinal analysis of drug trading on the darknet
      marketplace 'AlphaBay', which was the largest cryptomarket in operation. 1) Total
      sales volumes for the 'drugs' section was estimated at approximately USD 94
      million for the period from September 2015 to August 2016. 2) In addition, about
      64% of all sales are made with cocaine-, cannabis-, heroin-, and ecstasy-related
      products. 3) Average selling prices increase over time for categories including
      cannabis and hashish, ecstasy, opioids, psychedelics and stimulants. 4) The five
      most frequent countries of origin as indicated by vendors are the United States,
      United Kingdom, Australia, the Netherlands and Germany. Moreover, it was
      demonstrated that drug distribution on cryptomarkets is conducted at a regional
      rather than global level. 6) Furthermore, 4.88% of vendors made over USD 200,000
      and were responsible for 52.9% of total revenues generated over the period
      analysed. In contrast, 57.51% of vendors managed to sell drug items worth less
      than USD 10,000 within a period of twelve months. The findings suggest that
      'AlphaBay' was a cryptomarket mainly from and for Western industrialised
      countries. In contrast, countries of the global South are neither among the main
      countries of origin nor destination countries.

PMID- 29449106
TI  - Hair analysis in toxicological investigation of drug-facilitated crimes in
      Denmark over a 8-year period.
AB  - Hair can serve as a specimen for identifying past drug exposure. Segmental hair
      analysis may differentiate a single exposure from chronic use. Consequently,
      segmental hair analysis is useful for disclosing a single drug ingestion, as well
      as for determining repeated exposures in drug-facilitated crimes (DFCs). This
      paper presents an overview of toxicological investigations that have used hair
      analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were
      determined for 24 DFC-related drugs and metabolites, including benzodiazepines
      and other hypnotics, antihistamines, opioid analgesics, antipsychotics,
      barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC
      cases following a single or few intakes of chlorprothixene, codeine,
      diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported
      for the first time in forensic toxicology. A literature review on concentrations
      in the published DFC-related hair cases and on concentrations in hair of these
      substances after single and multiple doses is included. These cases demonstrate
      the value of segmental hair analysis in DFCs and facilitate future
      interpretations of results.

PMID- 29449107
TI  - A Model for Manganese interaction with Deinococcus radiodurans proteome network
      involved in ROS response and defense.
AB  - A complex network of regulatory proteins takes part in the mechanism underlying
      the radioresistance of Deinoccocus radiodurans bacterium (DR). The interaction of
      Mn(II) ions with DR-proteins and peptides seems to be responsible for proteins
      protection from oxidative damage induced by Reactive Oxygen Species during
      irradiation. In the present work we describe a combined approach of bioinformatic
      strategies based on structural data and annotation to predict the Mn(II)-binding
      proteins encoded by the genome of DR and, in parallel, the same predictions for
      other bacteria were performed; the comparison revealed that, in most of the
      cases, the content of Mn(II)-binding proteins is significantly higher in
      radioresistant than in radiosensitive bacteria. Moreover, we report the in silico
      protein-protein interaction network of the putative Mn(II)-proteins, remodeled in
      order to enhance the knowledge about the impact of Mn-binding proteins in DR
      ability to protect also DNA from various damaging agents such as ionizing
      radiation, UV radiation and oxidative stress.

PMID- 29449108
TI  - Effect of nitrogen and zinc fertilization on zinc and iron bioavailability and
      chemical speciation in maize silage.
AB  - Agronomic biofortification is one of the main strategies for alleviation of
      micronutrient deficiencies in food and feed. The objective of this study was to
      investigate the effect of N supply on total concentration of Zn and Fe and their
      chemical species in the soluble extracts of maize silage grown under field
      conditions. Total concentrations of Zn, Fe, Cu, Mn, S and P were measured by flow
      injection inductive coupled plasma (ICP) - mass spectrometer (MS). Soluble Fe and
      Zn were extracted and analyzed by size exclusion-inductively coupled plasma mass
      spectrometry. Using the same set-up for total elemental and speciation analysis
      enabled direct quantitative comparison of the detected speciated molecules with
      the total element sample content. N or Zn treatment, except in control plots, did
      not significantly affect concentrations of Zn and Fe in the maize silage and
      grain samples. Significant positive correlation was observed between Zn and Fe
      maize silage (r = 0.64, p < 0.01) and maize grain (r = 0.85, p < 0.01)
      concentrations. N and Zn treatment did not affect solubility of Zn and Fe, while
      available Zn and Fe were affected by increase in Zn soil treatment. Soluble Zn
      was speciated in LMW complexes, while soluble Fe was speciated in MMW and LMW
      complexes.

PMID- 29449109
TI  - Arsenic-containing hydrocarbons disrupt a model in vitro blood-cerebrospinal
      fluid barrier.
AB  - Lipid-soluble arsenicals, so-called arsenolipids, have gained a lot of attention
      in the last few years because of their presence in many seafoods and reports
      showing substantial cytotoxicity emanating from arsenic-containing hydrocarbons
      (AsHCs), a prominent subgroup of the arsenolipids. More recent in vivo and in
      vitro studies indicate that some arsenolipids might have adverse effects on brain
      health. In the present study, we focused on the effects of selected arsenolipids
      and three representative metabolites on the blood-cerebrospinal fluid barrier (B
      CSF-B), a brain-regulating interface. For this purpose, we incubated an in vitro
      model of the B-CSF-B composed of porcine choroid plexus epithelial cells (PCPECs)
      with three AsHCs, two arsenic-containing fatty acids (AsFAs) and three
      representative arsenolipid metabolites (dimethylarsinic acid, thio/oxo
      dimethylpropanoic acid) to examine their cytotoxic potential and impact on
      barrier integrity. The toxic arsenic species arsenite was also tested in this way
      and served as a reference substance. While AsFAs and the metabolites showed no
      cytotoxic effects in the conducted assays, AsHCs showed a strong cytotoxicity,
      being up to 1.5-fold more cytotoxic than arsenite. Analysis of the in vitro B-CSF
      B integrity showed a concentration-dependent disruption of the barrier within 72
      h. The correlation with the decreased plasma membrane surface area (measured as
      capacitance) indicates cytotoxic effects. These findings suggest exposure to
      elevated levels of certain arsenolipids may have detrimental consequences for the
      central nervous system.

PMID- 29449110
TI  - Impact of meteorological parameters on extracted landfill gas composition and
      flow.
AB  - The objective of this study was to investigate the impact of four pre-selected
      meteorological parameters (barometric pressure, wind speed, ambient temperature
      and solar radiation) on recovered landfill gas (LFG) flow, methane (CH4) content
      of the LFG and the recovered CH4 flow by performing statistical correlation tests
      and a visual check on correlations in scatterplots. Meteorological parameters
      were recorded at an on-site weather station, while LFG data were recorded when
      entering the gas engine. LFG CH4 concentration, LFG flow and CH4 flow correlated
      highly with both barometric pressure and changes in barometric pressure, and the
      correlations were statistically significant. A higher correlation was observed
      when studying changes in barometric pressure in comparison to the absolute value
      of barometric pressure. LFG recovery data correlated highly and significantly
      with wind speed during winter, but not during summer. Ambient temperature and
      solar radiation were not major meteorological parameters affecting LFG recovery,
      as low correlation coefficients were observed between these two parameters and
      the LFG recovery data.

PMID- 29449111
TI  - A comparative study of thermophilic and mesophilic anaerobic co-digestion of food
      waste and wheat straw: Process stability and microbial community structure
      shifts.
AB  - Renewable energy recovery from organic solid waste via anaerobic digestion is a
      promising way to provide sustainable energy supply and eliminate environmental
      pollution. However, poor efficiency and operational problems hinder its wide
      application of anaerobic digestion. The effects of two key parameters, i.e.
      temperature and substrate characteristics on process stability and microbial
      community structure were studied using two lab-scale anaerobic reactors under
      thermophilic and mesophilic conditions. Both the reactors were fed with food
      waste (FW) and wheat straw (WS). The organic loading rates (OLRs) were maintained
      at a constant level of 3 kg VS/(m3.d). Five different FW:WS substrate ratios were
      utilized in different operational phases. The synergetic effects of co-digestion
      improved the stability and performance of the reactors. When FW was mono
      digested, both reactors were unstable. The mesophilic reactor eventually failed
      due to volatile fatty acid accumulation. The thermophilic reactor had better
      performance compared to mesophilic one. The biogas production rate of the
      thermophilic reactor was 4.9-14.8% higher than that of mesophilic reactor
      throughout the experiment. The shifts in microbial community structures
      throughout the experiment in both thermophilic and mesophilic reactors were
      investigated. With increasing FW proportions, bacteria belonging to the phylum
      Thermotogae became predominant in the thermophilic reactor, while the phylum
      Bacteroidetes was predominant in the mesophilic reactor. The genus Methanosarcina
      was the predominant methanogen in the thermophilic reactor, while the genus
      Methanothrix remained predominant in the mesophilic reactor. The methanogenesis
      pathway shifted from acetoclastic to hydrogenotrophic when the mesophilic reactor
      experienced perturbations. Moreover, the population of lignocellulose-degrading
      microorganisms in the thermophilic reactor was higher than those in mesophilic
      reactor, which explained the better performance of the thermophilic reactor.

PMID- 29449112
TI  - Production of an innovative biowaste-derived fertilizer: Rapid monitoring of
      physical-chemical parameters by hyperspectral imaging.
AB  - In this work the possibility to apply hyperspectral imaging as a fast and non
      destructive technique for the monitoring of the production process at pilot plant
      scale of an innovative biowaste-derived fertilizer was explored. Different
      mixtures of urban organic waste, farm organic residues, biochar and vegetable
      active principles were selected and utilized in two different European countries,
      Italy and Spain, for the production of the innovative fertilizer. The biowaste
      derived fertilizer samples were collected from the pilot plant piles at different
      curing time and acquired by the hyperspectral imaging device. Spectra have been
      collected in the near infrared wavelength range (1000-1700 nm). Conventional
      analyses were carried out on the same samples in order to find correlations
      between the physical-chemical parameters detected at laboratory scale, and the
      acquired reflectance spectra. The investigated parameters were: pH, electrical
      conductivity, soluble total organic carbon and soluble total nitrogen.
      Hyperspectral data were processed adopting chemometric strategies through the
      application of principal component analysis, for exploratory purposes, and
      partial least squares analysis to establish correlations between spectral
      features and measured physical-chemical parameters. Good correlations, with R2
      ranging between 0.85 and 0.96, were obtained for all the investigated parameters.
      Results showed as the proposed approach, based on hyperspectral imaging, is
      suitable to be adopted for a rapid and non-destructive monitoring of waste
      derived fertilizer production.

PMID- 29449113
TI  - Characterization of the non-metal fraction of the processed waste printed circuit
      boards.
AB  - Electronic waste is one the fastest growing waste streams in the world and waste
      printed circuit boards (PCB) are the most valuable part of this stream due to the
      presence of gold, silver, copper, and palladium. The metal present in PCBs is
      mostly recovered for the market value whereas the nonmetal fractions are often
      ignored. This research explored the characteristics of the non-metal fraction
      (NMF) obtained after the processing of milled waste PCBs with a focus on
      responsible end-of-life solutions, in the form of non-hazardous landfilling or
      incineration. The NMF was characterized using sizing, assaying, loss on ignition,
      calorific value measurement, and thermogravimetric analysis (TGA). The result
      showed that the metal content in the NMF increased with decrease in the particle
      size for most of the metals except antimony and the result from loss on ignition
      (LOI) also showed that over 50% of the coarser fraction represented organic
      matter compared to less than 30% for the finest fraction. The study also showed
      that after the recovery of metals from the waste PCBs, landfill leaching for most
      of the metal is reduced below the environmental limits, with lead being the only
      exception. The lead leachate concentration of 18 mg/L was observed, which
      requires further treatment prior to landfilling. With an energy value of 16 GJ/t,
      the NMF could provide high energy recovery if incinerated but 194 mg/kg of
      hazardous flame retardants present in the NMF might be released if the combustion
      process is not closely monitored.

PMID- 29449114
TI  - Role of rain intensity and soil colloids in the retention of surfactant
      stabilized silver nanoparticles in soil.
AB  - Undisturbed outdoor lysimeters containing arable loamy sand soil were used to
      examine the influence of either heavy rain events (high frequency of high rain
      intensity), steady rain (continuous rainfall of low rain intensity), and natural
      rainfall on the transport and retention of surfactant-stabilized silver
      nanoparticles (AgNP). In addition, the AgNP-soil associations within the Ap
      horizon were analyzed by means of particle-size fractionation, asymmetrical flow
      field-flow fractionation coupled with UV/Vis-detection and inductively coupled
      plasma mass spectrometer (AF4-UV/Vis-ICP-MS), and transmission electron
      microscopy coupled to an energy-dispersive X-ray (TEM-EDX) analyzer. The results
      showed that AgNP breakthrough for all rain events was less than 0.1% of the total
      AgNP mass applied, highlighting that nearly all AgNP were retained in the soil.
      Heavy rain treatment and natural rainfall revealed enhanced AgNP transport within
      the Ap horizon, which was attributed to the high pore water flow velocities and
      to the mobilization of AgNP-soil colloid associations. Particle-size
      fractionation of the soil revealed that AgNP were present in each size fraction
      and therefore indicated strong associations between AgNP and soil. In particular,
      water-dispersible colloids (WDC) in the size range of 0.45-0.1 MUm were found to
      exhibit high potential for AgNP attachment. The AF4-UV/Vis-ICP-MS and TEM-EDX
      analyses of the WDC fraction confirmed that AgNP were persistent in soil and
      associated to soil colloids (mainly composed of Al, Fe, Si, and organic matter).
      These results confirm the particularly important role of soil colloids in the
      retention and remobilization of AgNP in soil. Furthermore, AF4-UV/Vis-ICP-MS
      results indicated the presence of single, homo-aggregated, and small AgNP
      probably due to dissolution.

PMID- 29449115
TI  - Single and combined effects of microplastics and mercury on juveniles of the
      European seabass (Dicentrarchus labrax): Changes in behavioural responses and
      reduction of swimming velocity and resistance time.
AB  - Microplastics and mercury are environmental pollutants of great concern. The main
      goal of the present study was to investigate the effects of these pollutants,
      both individually and in binary mixtures, on the swimming performance of juvenile
      European seabass, Dicentrarchus labrax. Microplastics alone, mercury alone and
      all the mixtures caused significant reduction of the swimming velocity and
      resistance time of fish. Moreover, changes in behavioural responses including
      lethargic and erratic swimming behaviour were observed. These results highlight
      that fish behavioural responses can be used as sensitive endpoint to establish
      the effects of contamination by microplastics and also emphasizes the need to
      assess the combined effects of microplastics and other environmental
      contaminants, with special attention to the effects on behavioural responses in
      fish and other aquatic species.

PMID- 29449117
TI  - Use of Nitrous Oxide in Maternity Care: AWHONN Practice Brief Number 6.

PMID- 29449116
TI  - Chronic impacts of oxytetracycline on mesophilic anaerobic digestion of excess
      sludge: Inhibition of hydrolytic acidification and enrichment of antibiotic
      resistome.
AB  - We evaluated the chronic impact of oxytetracycline (OTC) on performance and
      antibiotic resistance development during the mesophilic anaerobic digestion (AD)
      of antibiotic-containing biomass. Mesophilic AD was conducted in a completely
      stirred tank reactor by constantly feeding municipal excess sludge spiked with
      increasing concentrations of OTC (0-1000 mg L-1) under a solid retention time of
      20 days over a period of 265 days. Results showed that methane generation of
      mesophilic AD was inhibited when the OTC concentration in digested sludge was
      increased to around 18,000 mg kg-1 (OTC dose, 1000 mg L-1), due to the inhibition
      of fermenting and acidogenic bacteria. Metagenomic sequencing and high-throughput
      quantitative PCR analysis demonstrated that tetracycline resistance genes were
      the most dominant type (38.47-43.76%) in the resistome, with tetG, tetX, tetM,
      tetR, tetQ, tetO, and tetL as the dominant resistant subtypes throughout the
      whole experimental period. The relative abundance of these tet genes increased
      from 2.10 * 10-1 before spiking OTC (OTC concentration in digested sludge, 8.97
      mg kg-1) to 2.83 * 10-1 (p < 0.05) after spiking OTC at a dose of 40 mg L-1 (OTC
      concentration in digested sludge, 528.52 mg kg-1). Furthermore, mobile genetic
      elements, including integrons, transposons, and plasmids, were also enriched with
      the increase in OTC dose. Based on partial canonical correspondence analysis, the
      contributions of horizontal (mobile element alteration) and vertical (bacterial
      community shift) gene transfer to antibiotic resistome variation were 29.35% and
      21.51%, respectively. Thus, considering the inhibition of hydrolytic
      acidification and enrichment of antibiotic resistome, mesophilic AD is not
      suggested to directly treat the biomass containing OTC concentration higher than
      200 mg L-1.

PMID- 29449118
TI  - Shot by a Gun ... Missed by a Provider.
AB  - BACKGROUND: Botulism is a paralytic disease caused by the neurotoxin produced by
      Clostridium botulinum. The majority of cases are due to ingestion or injection
      drug use. Wound botulism from traumatic injury is exceedingly rare, with only one
      to two cases reported each year in the United States. CASE REPORT: A 27-year-old
      man presented to the Emergency Department with diplopia, dysphagia, and
      progressive weakness 10 days after sustaining a gunshot wound to his right lower
      leg. He had been evaluated for the same complaints at a different facility the
      day prior and was discharged. His wound appeared well-healing, but a high
      suspicion for wound botulism led to rapid consultation with the state Poison
      Control Center and the Centers for Disease Control and Prevention. The patient
      developed worsening respiratory insufficiency and required mechanical
      ventilation. Expeditious treatment with equine heptavalent botulinum antitoxin
      resulted in significant recovery of strength in 4 days. Serum toxin bioassay
      tested positive for botulinum neurotoxin type A. WHY SHOULD AN EMERGENCY
      PHYSICIAN BE AWARE OF THIS?: Wound botulism now accounts for the majority of
      adult botulism in the United States. It should be considered in any patient with
      signs of neuromuscular disease and a recent injury, even if the wound appears
      uninfected.

PMID- 29449119
TI  - Violence Against Health Care Providers: A Mixed-Methods Study from Karachi,
      Pakistan.
AB  - BACKGROUND: Violence against health care providers (HCPs) remains a significant
      public health problem in developing countries, affecting their performance and
      motivation. OBJECTIVES: To report the quantity and perceived causes of violence
      committed upon HCPs and identify strategies intended to prevent and de-escalate
      it. METHODS: This was a mixed-methods concurrent study design (QUAN-QUAL). A
      structured questionnaire was filled in on-site by trained data collectors for
      quantitative study. Sites were tertiary care hospitals, local nongovernmental
      organizations (NGOs) providing health services, and ambulance services.
      Qualitative data were collected through in-depth interviews and focus group
      discussions at these same sites, as well as with other stakeholders including
      media and law enforcement agencies. RESULTS: One-third of the participants had
      experienced some form of violence in the last 12 months. Verbal violence was
      experienced more frequently (30.5%) than physical violence (14.6%). Persons who
      accompanied patients (58.1%) were found to be the chief perpetrators. Security
      staff and ambulance staff were significantly more likely to report physical
      violence (p = 0.001). Private hospitals and local NGOs providing health services
      were significantly less likely to report physical violence (p = 0.002). HCPs
      complained about poor facilities, heavy workload, and lack of preparedness to
      deal with violence. The deficiencies highlighted predominantly included
      inadequate security and lack of training to respond effectively to violence. Most
      stakeholders thought that poor quality of services and low capacity of HCPs
      contributed significantly to violent incidents. CONCLUSION: There is a great need
      to design interventions that can help in addressing the behavioral,
      institutional, and sociopolitical factors promoting violence against HCPs. Future
      projects should focus on designing interventions to prevent and mitigate violence
      at multiple levels.

PMID- 29449120
TI  - Bilateral Phlegmasia Cerulea Dolens After Warfarin Reversal for Acute Rectal
      Bleeding: A Case Report.
AB  - BACKGROUND: Deep vein thrombosis (DVT) is a common disease that is diagnosed in
      approximately 1 in 1000 adults annually. Extensive DVT can lead to life- or limb
      threatening diagnoses such as phlegmasia cerulea dolens (PCD), phlegmasia alba
      dolens, and venous gangrene. PCD, also known as massive iliofemoral venous
      thrombosis, is rare, and a severe complication of DVT. CASE REPORT: We report a
      case of a 94-year-old bedridden woman with past medical history of dementia,
      hypertension, pulmonary embolism, DVT, and atrial fibrillation. The patient was
      admitted to the hospital for bright red blood per rectum and an elevated
      international normalized ratio (INR) of 5.7. On admission, her dose of warfarin
      was suspended and she was given 4 units of fresh frozen plasma as well as 10 mg
      of i.v. vitamin K. She was discharged home with an INR normalized to 1.3 and
      cessation of her rectal bleeding. At discharge, she was not restarted on
      warfarin, nor was any bridging therapy used. The patient returned to the
      Emergency Department a week later for worsening pain and bluish discoloration of
      her bilateral lower extremities. An ultrasound (US) examination showed that she
      had developed bilateral PCD, after INR reversal. WHY SHOULD AN EMERGENCY
      PHYSICIAN BE AWARE OF THIS?: Emergency physicians commonly care for patients who
      present with acute DVT or treat patients on anticoagulant therapy who require
      cessation of medications or administration of prothrombotic agents to reverse
      bleeding. Cases of extensive clot burden leading to PCD have been reported in the
      literature, however, reports of bilateral PCD secondary to cessation of warfarin
      have been scarce. PCD should be considered carefully as one of the complications
      in warfarin reversal, as it requires immediate attention and surgical
      intervention to prevent limb loss.

PMID- 29449121
TI  - Sleep disorders and Parkinson disease; lessons from genetics.
AB  - Parkinson disease is a common, age-related neurodegenerative disorder, projected
      to afflict millions of individuals in the near future. Understanding its etiology
      and identifying clinical, genetic or biological markers for Parkinson disease
      onset and progression is therefore of major importance. Various sleep-related
      disorders are the most common group of non-motor symptoms in advanced Parkinson
      disease, but they can also occur during its prodromal phase. However, with the
      exception of REM sleep behavior disorder, it is unclear whether they are part of
      the early pathological process of Parkinson disease, or if they develop as
      Parkinson disease advances because of treatments and neurodegeneration
      progression. The advancements in genetic studies in the past two decades have
      generated a wealth of information, and recent genetic studies offer new insight
      on the association of sleep-related disorders with Parkinson disease. More
      specifically, comparing genetic data between Parkinson disease and sleep-related
      disorders can clarify their association, which may assist in determining whether
      they can serve as clinical markers for Parkinson disease risk or progression. In
      this review, we discuss the current knowledge on the genetics of sleep-related
      disorders in Parkinson disease context, and the potential implications on
      research, diagnosis, counseling and treatment.

PMID- 29449122
TI  - Non-pharmacological interventions for improving postpartum maternal sleep: A
      systematic review and meta-analysis.
AB  - Evidence suggests that poor postpartum sleep quality is a risk factor for the
      development of postpartum depression. As such, non-pharmacological interventions
      have been developed to help improve sleep in the postpartum period. The primary
      aims of this systematic review and meta-analysis were to determine if non
      pharmacological interventions improved maternal sleep and to compare the
      effectiveness of different intervention types. Secondary aims included examining
      effects on maternal mood and infant sleep. We searched MEDLINE, EMBASE, CINAHL,
      PsycINFO, and Web of Science from their inceptions to September 2017 and found 15
      eligible studies. Non-pharmacological sleep interventions were found to improve
      subjective reports of maternal sleep (Cohen's d = -0.54, 95%CI = -0.88 to -0.19).
      Massage (Cohen's d = -1.07 95%CI = -1.34 to -0.79) and exercise (Cohen's d = 
      0.82 95%CI = -1.28 to -0.37) interventions had the largest impact on maternal
      sleep quality. Positive effects on nocturnal infant sleep were found for
      interventions overall (Cohen's d = -0.27 95%CI = -0.52 to -0.02) but not for
      maternal depression (Cohen's d = -0.08 95%CI = -0.28 to 0.12). Despite evidence
      suggesting improvements in subjective maternal sleep, more research must be
      conducted on the durability of effects of non-pharmacological interventions using
      objective measures of sleep quality.

PMID- 29449123
TI  - Early Impact of Medicaid Expansion and Quality of Breast Cancer Care in Kentucky.
AB  - BACKGROUND: In January 2014, Kentucky expanded Medicaid coverage to include all
      individuals and families with incomes up to 33% above the federal poverty line.
      This study evaluated the early impact of Medicaid expansion on some aspects of
      the quality of breast cancer care in Kentucky. STUDY DESIGN: The Kentucky Cancer
      Registry was queried for all women aged 20 to 64 years diagnosed with breast
      cancer between 2011 and 2016. Demographic, tumor, and treatment characteristics
      were assessed for each year during this interval. To evaluate the association
      between Medicaid expansion and these parameters, these variables, along with
      quality metrics deriving from said variables, were compared for the years 2011 to
      2013 (pre) and the years 2014 to 2016 (post). RESULTS: Of 13,625 women with
      breast cancer, 11,915 (59.5%) were diagnosed and treated from 2011 to 2013, and
      8,127 (40.5%) were diagnosed and treated from 2014 to 2016. After Medicaid
      expansion, fewer patients were uninsured (3.7% post vs 1.0% pre) and more were
      covered by Medicaid (15.9% post vs 10.9% pre) (p < 0.001). There was increased
      diagnosis of early stage (I and II) breast cancer (p = 0.002) and an increasing
      proportion of women undergoing breast-conservation therapy (p < 0.001). Time from
      diagnosis to operation increased (p < 0.001), time from operation to chemotherapy
      remained unchanged (p = 0.26) and time from operation to radiation decreased (p <
      0.001). CONCLUSIONS: The expansion of Kentucky Medicaid in 2014 has been
      associated with earlier diagnosis and somewhat improved quality of breast cancer
      care, despite a stable disease incidence. Additional improvements in treatment
      expediency will require improvements in patient outreach and healthcare
      infrastructure.

PMID- 29449124
TI  - Investigating PKA-RII specificity using analogs of the PKA:AKAP peptide inhibitor
      STAD-2.
AB  - Generation of the second messenger molecule cAMP mediates a variety of cellular
      responses which are essential for critical cellular processes. In response to
      elevated cAMP levels, cAMP dependent protein kinase (PKA) phosphorylates serine
      and threonine residues on a wide variety of target substrates. In order to
      enhance the precision and directionality of these signaling events, PKA is
      localized to discrete locations within the cell by A-kinase anchoring proteins
      (AKAPs). The interaction between PKA and AKAPs is mediated via an amphipathic
      alpha-helix derived from AKAPs which binds to a stable hydrophobic groove formed
      in the dimerization/docking (D/D) domain of PKA-R in an isoform-specific fashion.
      Although numerous AKAP disruptors have previously been identified that can
      inhibit either RI- or RII-selective AKAPs, no AKAP disruptors have been
      identified that have isoform specificity for RIalpha versus RIbeta or RIIalpha
      versus RIIbeta. As a strategy to identify isoform-specific AKAP inhibitors, a
      library of chemically stapled protein-protein interaction (PPI) disruptors was
      developed based on the RII-selective AKAP disruptor, STAD-2. An alanine was
      substituted at each position in the sequence, and from this library it was
      possible to delineate the importance of longer aliphatic residues in the
      formation of a region which complements the hydrophobic cleft formed by the D/D
      domain. Interestingly, lysine residues that were added to both terminal ends of
      the peptide sequence to facilitate water solubility appear to contribute to
      isoform specificity for RIIalpha over RIIbeta while having only weak interaction
      with RI. This work supports current hypotheses on the mechanisms of AKAP binding
      and highlights the significance of particular residue positions that aid in
      distinguishing between the RII isoforms and may provide insight into future
      design of isoform-selective AKAP disruptors.

PMID- 29449125
TI  - Enhancing the anti-biofilm activity of 5-aryl-2-aminoimidazoles through nature
      inspired dimerisation.
AB  - The increased tolerance of biofilms against disinfectants and antibiotics has
      stimulated research into new methods of biofilm prevention and eradication. In
      our previous work, we have identified the 5-aryl-2-aminoimidazole core as a
      scaffold that demonstrates preventive activity against biofilm formation of a
      broad range of bacterial and fungal species. Inspired by the dimeric nature of
      natural 2-aminoimidazoles of the oroidin family, we investigated the potential of
      dimers of our decorated 5-aryl-2-aminoimidazoles as biofilm inhibitors. A
      synthetic approach towards 2-aminoimidazole dimers linked by an alkyl chain was
      developed and a total of 48 dimers were synthesized. The linkers were introduced
      at two different positions, the N1-position or the N2-position, and the linker
      length and the substitution of the 5-phenyl ring (H, F, Cl, Br) were varied.
      Although, no clear correlation between linker length and biofilm inhibition was
      observed, a strong increase in anti-biofilm activity for almost all N1,N1'-linked
      dimers was obtained, compared to the respective monomers against Salmonella
      Typhimurium, Escherichia coli and Staphylococcus aureus. The N2,N2'-linked
      dimers, having a H- or F-substitution, were also found to show a strong increase
      in anti-biofilm activity compared to the respective monomers against these three
      bacterial species and against Pseudomonas aeruginosa. In addition, the obtained
      growth measurements suggest a broad concentration range with specific biofilm
      inhibition and no effect on the planktonic growth against Salmonella Typhimurium
      and Pseudomonas aeruginosa.

PMID- 29449126
TI  - Thrombelastography Suggests Hypercoagulability in Patients with Renal Dysfunction
      and Intracerebral Hemorrhage.
AB  - BACKGROUND: The objective of this study was to quantify coagulopathy using
      thrombelastography (TEG) in patients with renal dysfunction and intracerebral
      hemorrhage (ICH). METHODS: We reviewed patients admitted with spontaneous ICH
      between November 2009 and May 2015. TEG was performed at the time of admission.
      Creatinine clearance (CCr) was calculated using the Cockroft-Gault equation.
      Patients were divided into 2 groups based on normal (CCr >= 90) or reduced renal
      function (CCr < 90). Multivariable regression models were conducted to compare
      the differences of TEG components. RESULTS: A total of 120 patients were included
      in the analysis. The normal CCr group was younger (56.1 versus 62.3 years, P <
      .01), was more often male (73.6% versus 53.7%, P = .03), and had higher mean
      admission hemoglobin (14.2 versus 13.2 mEq/L, P < .01) than the reduced renal
      function group. The 2 groups were similar with respect to antiplatelet or
      anticoagulant use, coagulation studies, and baseline ICH volume. Following
      multivariate analysis, the reduced renal function group was found to have shorter
      K (1.5 versus 2.2 min, P = 004), increased angle (66 versus 62.2 degrees, P =
      .04), increased MA (67.3 versus 62.3, P = .02), and increased G (11.3 versus 9.9
      dynes/cm2, P = .04) compared with the normal group. Mortality, poor functional
      outcome (modified Rankin Scale score 4-6), hematoma enlargement, hospital length
      of stay, and surgical interventions were not different between the 2 groups.
      CONCLUSIONS: Patients with ICH and reduced CCr display faster clotting rate and
      increased clot strength, suggesting that patients with renal dysfunction present
      with a relatively hypercoagulable state based on TEG parameters thought to
      reflect platelet activity.

PMID- 29449127
TI  - Evaluating the Effect of Six Proton Pump Inhibitors on the Antiplatelet Effects
      of Clopidogrel.
AB  - BACKGROUND AND GOAL: Cytochrome P450 (CYP) enzymes are responsible for the
      conversion of clopidogrel into its active metabolite and the metabolism of proton
      pump inhibitors (PPIs), which may also inhibit CYP enzymes. A current Food and
      Drug Administration advisory suggests avoiding esomeprazole and omeprazole while
      taking clopidogrel because of concerns that PPIs may compromise clopidogrel's
      antiplatelet effects. The objective of the present study was to examine the
      robustness of this interaction using a well-controlled study design in a
      population of participants free of confounders. MATERIALS AND METHODS: Twenty
      eight healthy male participants, with a mean age 24.2 +/- 3.2, were randomized to
      an incomplete crossover design schedule. Participants underwent platelet
      aggregation testing after clopidogrel alone, while on clopidogrel in combination
      with 1 of 3 PPIs (40 mg of pantoprazole, 20 mg of omeprazole, 20 mg of
      rabeprazole, 40 mg of esomeprazole, 30 mg of lansoprazole, or 30 mg of
      dexlansoprazole), and during 1 week of clopidogrel-only washout periods.
      FINDINGS: The median platelet aggregation to adenosine diphosphate during a drug
      free baseline was 10Omega (2.5 interquartile range) of impedance and decreased to
      0Omega on clopidogrel alone. Aggregation did not significantly change with
      concomitant use of PPIs and clopidogrel. CONCLUSION: These data do not
      demonstrate a significant interaction between common individual PPIs and
      clopidogrel in healthy volunteers who respond to clopidogrel alone. This adds
      data to a growing body of evidence indicating that the addition of a PPI may have
      a weak effect on clopidogrel's antiplatelet properties, and may only be relevant
      in specific clinical circumstances.

PMID- 29449128
TI  - Meta-Analysis on the Association between Brain-Derived Neurotrophic Factor
      Polymorphism rs6265 and Ischemic Stroke, Poststroke Depression.
AB  - BACKGROUND: Ischemic stroke is a multifactorial neurologic injury that causes
      mortality and disability worldwide. Poststroke depression is the most important
      neuropsychiatric consequence of stroke. Brain-derived neurotrophic factor is a
      neurotrophin family member that plays key role in regulating neuron survival and
      differentiation. Studies found a polymorphism in brain-derived neurotrophic
      factor gene (rs6265) may associate with the ischemic stroke and poststroke
      depression risk. However, the results are inconclusive and inconsistent. METHODS:
      In the present meta-analysis, the database PubMed, Embase, Cochrane Central
      Register of Controlled Trials, CNKI, and Chinese Biomedical Literature Database
      were searched until July 9, 2017. RESULTS: Seven studies with 1287 cases and 1032
      controls were included for the meta-analysis of ischemic stroke, and five studies
      with 272 cases and 503 controls were included for poststroke depression. The
      results indicated that the GG genotype of brain-derived neurotrophic factor is
      related to a significantly lower risk of ischemic stroke in the homozygous and
      dominant models (odds ratio = .57 and .80, respectively). No significant relation
      was found between rs6265 and poststroke depression. CONCLUSIONS: Thus, brain
      derived neurotrophic factor rs6265 might be recommended as a predictor of
      susceptibility of ischemic stroke. However, the results of this meta-analysis
      should be interpreted with caution because of the heterogeneity between studies
      and low sample size. Further studies are needed to evaluate the associations
      between rs6265 and poststroke depression, especially in Caucasians, with large
      sample size.

PMID- 29449129
TI  - Sub-minimum inhibitory concentrations of ceftazidime inhibit Pseudomonas
      aeruginosa biofilm formation.
AB  - Pseudomonas aeruginosa exhibits the biofilm mode of growth and causes chronic as
      well as acute infections in humans. Several reports have shown that the
      treatments with sub-minimum inhibitory concentrations (sub-MICs) of antimicrobial
      agents influence biofilm formation by P. aeruginosa. The antibiotic ceftazidime
      (CAZ) is used to treat P. aeruginosa infections, but few studies have examined
      the effects of beta-lactams on biofilm formation by P. aeruginosa. In this study,
      we investigated the role of sub-MICs of CAZ in the formation of P. aeruginosa
      biofilms. 1/4 * MIC CAZ reduced the biofilm volume of P. aeruginosa PAO1, as
      quantified by crystal violet staining. The formation of P. aeruginosa PAO1
      biofilms treated with 1/4 * MIC CAZ were observed by confocal laser scanning
      microscopy. They were more heterogeneous than the PAO1 biofilms without CAZ
      treatment. Furthermore, sub-MICs of CAZ inhibited the twitching motility, which
      played an important role in mature biofilm formation. 1/4 * MIC CAZ also reduced
      the gene expressions of lecA, lecB, pel and psl, which mediate the adhesion and
      polysaccharide matrix synthesis of P. aeruginosa. These effects suggest that sub
      MICs of CAZ may affect a number of stages of biofilm formation. Investigating the
      effects of sub-MIC antibiotics on targeted bacterial biofilm may lead to the
      development of future antibiotic treatment modalities.

PMID- 29449130
TI  - The NASA Task Load Index as a measure of overall workload among neonatal,
      paediatric and adult intensive care nurses.
AB  - INTRODUCTION: The NASA Task Load Index (NASA-TLX) is a subjective workload
      assessment scale developed for use in aviation and increasingly applied to
      healthcare. The scale purports to measure overall workload as a single variable
      calculated by summing responses to six items. Since no data address the validity
      of this scoring approach in health care, we evaluated the single factor structure
      of the NASA-TLX as a measure of overall workload among intenisive care nurses.
      METHODS: Confirmatory factor analysis of data from two studies of nurse workload
      in neonatal, paediatric, and adult intensive care units. Study 1 data were
      obtained from 136 nurses in one neonatal intensive care unit. Study 2 data were
      collected from 300 nurses in 17 adult, paediatric and neonatal units. Nurses
      rated their workload using the NASA-TLX's paper version. RESULTS: A single factor
      model testing whether all six items measured a single overall workload variable
      fit least well (RMSEA = 0.14; CFI = 0.91; TLI = 0.85). A second model that
      specified two items as outcomes of overall workload had acceptable fit (RMSEA =
      0.08; CFI = 0.97; TLI = 0.95) while a third model of four items fit best (RMSEA =
      0.06; CFI > 0.99; TLI = 0.99). CONCLUSION: A summed score from four of six NASA
      TLX items appears to most reliably measure a single overall workload variable
      among intensive care nurses.

PMID- 29449131
TI  - The treatment of anti-phospholipid syndrome: A comprehensive clinical approach.
AB  - Anti-phospholipid syndrome (APS) is an acquired pro-thrombotic autoimmune disease
      that predisposes to thrombotic events and/or obstetric complications, in the
      persistent presence of anti-phospholipid antibodies (aPL). Life long moderate
      intensity anticoagulation is the option of choice for aPL-positive patients with
      a previous thrombosis; critical issues concern the management of those with a
      history of arterial event due to the high rate of recurrence. Alternatives
      comprise anti-platelet agents and high-intensity anticoagulation. Low dose
      aspirin (LDASA) and low molecular weight heparin provide the mainstay of the
      treatment of obstetric APS, allowing a birth rate in 70% of cases. The management
      of refractory APS, thrombotic as well as obstetric, is highly debated, but an
      increasing burden of evidence points towards the beneficial effects of multiple
      treatments. Similarly, a management envisaging multiple drugs (anticoagulation,
      steroids, plasma exchange and/or intravenous immunoglobulins) is the most
      effective approach in catastrophic APS. Asymptomatic aPL carriers are at higher
      risk of thrombotic and obstetric complications compared to the general
      population, thus potentially benefitting of a pharmacological intervention. LDASA
      and hydroxychloroquine can be considered as options, in particular in case of
      high risk aPL profile, concomitant cardiovascular risk factors or associated
      autoimmune disease. APS is apparently a simple condition, but its multifaceted
      nature requires a complex and tailored treatment.

PMID- 29449132
TI  - E-cigarettes Associated With Depressed Smoking Cessation: A Cross-sectional Study
      of 28 European Union Countries.
AB  - INTRODUCTION: Electronic cigarettes (e-cigarettes) are often promoted to assist
      with cigarette smoking cessation. In 2016-2017, the relationship between e
      cigarette use and having stopped smoking among ever (current and former) smokers
      was assessed in the European Union and Great Britain by itself. METHODS: Cross
      sectional logistic regression of the association between being a former smoker
      and e-cigarette use was applied to the 2014 Eurobarometer survey of 28 European
      Union countries controlling for demographics. RESULTS: Among all ever smokers,
      any regular ever use of nicotine e-cigarettes was associated with lower odds of
      being a former smoker (unadjusted OR=0.34, 95% CI=0.26, 0.43, AOR=0.43, 95%
      CI=0.32, 0.58) compared with smokers who had never used e-cigarettes. In
      unadjusted models, daily use (OR=0.42, 95% CI=0.31, 0.56); occasional use
      (OR=0.25, 95% CI=0.18, 0.35); and experimentation (OR=0.24, 95% CI=0.19, 0.30) of
      nicotine e-cigarettes were associated with lower odds of being a former smoker
      compared with having never used nicotine-containing e-cigarettes. Comparable
      results were found in adjusted models. Results were similar in Great Britain
      alone. Among current smokers, daily cigarette consumption was 15.6 cigarettes/day
      (95% CI=14.5, 16.7) among those who also used e-cigarettes versus 14.4
      cigarettes/day (95% CI=13.4, 15.4) for those who did not use them (p<0.05).
      CONCLUSIONS: These results suggest that e-cigarettes are associated with
      inhibiting rather than assisting in smoking cessation. On the population level,
      the net effect of the entry of e-cigarettes into the European Union (and Great
      Britain) is associated with depressed smoking cessation of conventional
      cigarettes.

PMID- 29449133
TI  - Evaluation of Medicare's Intensive Behavioral Therapy for Obesity: the BieneStar
      Experience.
AB  - INTRODUCTION: In 2011, the Centers for Medicare and Medicaid Services began to
      reimburse primary care providers for intensive behavior therapy for obesity. This
      study evaluated a Centers for Medicare and Medicaid Services intensive behavior
      therapy for obesity program as implemented in primary care clinics. METHODS: Data
      for this retrospective cohort study were obtained between May 2012 and February
      2015 and statistical analysis was performed in 2017. The sample included 643
      participants who attended at least one BieneStar intensive behavior therapy for
      obesity program session. The primary outcome was weight, and covariates were
      number of sessions, age, race/ethnicity, diagnosis of hypertension and diabetes,
      and type of health insurance. RESULTS: Of 643 participants that initiated the
      BieneStar program, 641 had complete data. The median reduction in weight of
      participants was as follows: those who attended fewer than four sessions, 0 kg
      (95% CI=0, 0.11 kg); between four and eight sessions, 1.1 kg (95% CI=0.86, 1.59
      kg); and more than eight sessions 3.7 kg (95% CI=3.36, 4.55 kg). Medians of
      weight were significantly different between each classification of session
      numbers (p<0.01). Participants lost on average 0.102 kg of weight per session
      attended. CONCLUSIONS: The BieneStar program showed that the weight of
      participants decreased as they attended more sessions. Further studies are needed
      to determine if these results can be reproduced in other office-based primary
      care clinics and the program's impact on chronic disease.

PMID- 29449134
TI  - Characterizing Sexual Violence Victimization in Youth: 2012 National Intimate
      Partner and Sexual Violence Survey.
AB  - INTRODUCTION: Youth sexual violence victimization is an urgent public health
      concern that can lead to a variety of health problems and increased risk for
      victimization during adulthood. Examining the characteristics of early
      victimization and their association with subsequent victimization during
      adulthood may help strengthen primary prevention efforts. METHODS: Data are from
      the 2012 National Intimate Partner and Sexual Violence Survey. Prevalence
      estimates were computed in 2017 for rape and made to sexually penetrate, their
      subtypes, as well as proportions among victims by type of perpetrator. Chi-square
      tests of association were conducted between youth sexual violence victimization
      and the same experiences in adulthood. RESULTS: Approximately 10 million U.S.
      females (8.4%) experienced completed or attempted rape and 1.9 million U.S. males
      (1.6%) were made to penetrate someone during youth. Most victims knew their
      perpetrators. Being raped or made to penetrate during youth was associated with
      increased likelihood of such victimization in adulthood. CONCLUSIONS: Females and
      males experience youth sexual violence victimization at alarming rates. Primary
      prevention efforts with youth are critical to prevent early victimization,
      subsequent victimization in adulthood, and the mental and physical health
      consequences associated with sexual violence victimization.

PMID- 29449135
TI  - Effects of Before-School Physical Activity on Obesity Prevention and Wellness.
AB  - INTRODUCTION: The effects of Build Our Kids Success-a 12-week, 1-hour before
      school physical activity program-on BMI and social-emotional wellness among
      kindergarten to eighth grade students was examined. STUDY DESIGN: This was a
      nonrandomized trial. SETTING/PARTICIPANTS: Participants were from 24 schools in
      Massachusetts; there were 707 children from kindergarten to eighth grade.
      INTERVENTION: Children registered for Build Our Kids Success in 2015-2016
      participated in a 2 days/week or 3 days/week program. Nonparticipating children
      served as controls. MAIN OUTCOME MEASURES: At baseline and 12 weeks, study staff
      measured children's heights/weights; children aged >=8 years completed surveys.
      Main outcomes were 12-week change in BMI z-score, odds of a lower BMI category at
      follow-up, and child report of social-emotional wellness. Analyses were completed
      in March-June 2017. RESULTS: Follow-up BMI was obtained from 67% of children and
      self-reported surveys from 72% of age-eligible children. Children in the 3
      days/week group had improvements in BMI z-score (-0.22, 95% CI= -0.31, -0.14) and
      this mean change was significantly different than the comparison group (-0.17
      difference, 95% CI= -0.27, -0.07). Children in the 3 days/week group also had
      higher odds of being in a lower BMI category at follow-up (OR=1.35, 95% CI=1.12,
      1.62); significantly different than the comparison group (p<0.01). Children in
      the 2 days/week program had no significant changes in BMI outcomes. Children in
      the 3 days/week group demonstrated improvement in their student engagement scores
      (0.79 units, p=0.05) and had nonsignificant improvements in reported peer
      relationships, affect, and life satisfaction versus comparison. The 2 days/week
      group had significant improvements in positive affect and vitality/energy versus
      comparison. CONCLUSIONS: A 3 days/week before-school physical activity program
      resulted in improved BMI and prevented increases in child obesity. Both Build Our
      Kids Success groups had improved social-emotional wellness versus controls. TRIAL
      REGISTRATION: This study is registered at www.clinicaltrials.gov NCT03190135.

PMID- 29449136
TI  - Sexual Orientation Discordance and Nonfatal Suicidal Behaviors in U.S. High
      School Students.
AB  - INTRODUCTION: Studies among adults have documented association between sexual
      orientation discordance and some suicide risk factors. However, studies examining
      sexual orientation discordance and nonfatal suicidal behaviors in youth are rare.
      This study examines the association between sexual orientation discordance and
      suicidal ideation/suicide attempts among a nationally representative sample of
      U.S. high school students. METHODS: Using sexual identity and sex of sexual
      contact measures from the 2015 national Youth Risk Behavior Survey (n=6,790), a
      sexual orientation discordance variable was constructed describing concordance
      and discordance (agreement and disagreement, respectively, between sexual
      identity and sex of sexual contacts). Three suicide-related questions (seriously
      considered attempting suicide, making a plan about how they would attempt
      suicide, and attempting suicide) were combined to create a two-level nonfatal
      suicide risk variable. Analyses were restricted to students who identified as
      heterosexual or gay/lesbian, who had sexual contact, and who had no missing data
      for sex or suicide variables. The association between sexual orientation
      discordance and nonfatal suicide risk was assessed using logistic regression.
      Analyses were performed in 2017. RESULTS: Approximately 4.0% of students
      experienced sexual orientation discordance. High suicide risk was significantly
      more common among discordant students compared with concordant students (46.3% vs
      22.4%, p<0.0001). In adjusted models, discordant students were 70% more likely to
      have had suicidal ideation/suicide attempts compared with concordant students
      (adjusted prevalence ratio=1.7, 95% CI=1.4, 2.0). CONCLUSIONS: Sexual orientation
      discordance was associated with increased likelihood of nonfatal suicidal
      behaviors. Discordant adolescents may experience unique stressors that should be
      considered when developing and implementing suicide prevention programs.

PMID- 29449138
TI  - Driving with drug-resistant and controlled seizures from a patient's perspective:
      Assessment of attitudes and practices.
AB  - BACKGROUND: Driving restrictions in epilepsy are intended to safeguard public and
      personal safety; however, these limitations inhibit socialization, restrict
      employment, and reduce self-esteem in patients with seizures. A large proportion
      of patients with seizures continue to drive, and factors leading to noncompliance
      with driving regulations are poorly understood. Thus, the patients' perspective
      on driving safety is not incorporated into the existing counseling tools on
      driving safety in epilepsy. The present study assessed social, economic, and
      psychological perceptions related to driving restrictions in patients with
      refractory and pharmacotherapy-controlled seizures at the single epilepsy center
      and identified impediments for safe driving. METHODS: Data were obtained from an
      anonymous survey completed by 25 adult patients in the presurgical group (PG)
      with refractory epilepsy and 46 patients in the ambulatory group (AG) with
      confirmed epilepsy which did not meet criteria for refractoriness. The
      questionnaire (administered via Research Electronic Data Capture (REDCap))
      addressed seizure and driving history, knowledge of driving restrictions, and
      social consequences of losing driving privileges. RESULTS: Eighty-seven percent
      of all responders experienced seizures with alteration of awareness; however, 34%
      of patients continued to drive during the time when they were legally restricted,
      and 6% had accidents related to seizures. All responders reported their seizure
      status accurately to the treating physician, and 93% understood state-based
      driving restrictions. The median time from the last seizure was shorter, and the
      duration of last driving restriction was longer in the PG compared with the AG (1
      vs. 20weeks, and 12 vs. 24weeks, respectively). Despite that, the proportions of
      patients driving at the time of survey were not significantly different between
      the two groups. Nearly 80% of all patients stated that driving restrictions
      reduced their quality of life, and 70% believed that these restrictions carry a
      social stigma. Employment was chosen to be the most affected by driving
      restrictions from a list of four social domains by the majority of patients in
      both groups. Notably, the employment rate was 26% higher in the AG compared with
      the PG. The lack of public transportation was regarded as a hurdle by more than
      60% of patients in each group with greater than two-thirds of patients relying on
      other drivers for transportation. CONCLUSIONS: These findings suggest that
      patients with refractory and pharmacotherapy-controlled seizures are similarly
      likely to drive a vehicle, disregarding a practitioner's advice and state
      restrictions. The lack of public transportation is a shared constraint and likely
      leads to reduced compliance with driving regulations. Driving restrictions carry
      social stigma and limit the employment of patients with epilepsy, regardless of
      the refractory seizure status.

PMID- 29449137
TI  - Sex-specific differences in insulin resistance in type 1 diabetes: The CACTI
      cohort.
AB  - OBJECTIVE: To test the hypothesis that multitissue deficits in insulin
      sensitivity are greater among women than men with type 1 diabetes compared to
      respective controls. RESEARCH DESIGN AND METHODS: Three-stage hyperinsulinemic
      euglycemic clamps (4, 8, 40 mU/m2/min) were performed on 41 people with type 1
      diabetes and 47 adults without diabetes (mean +/- SD age 46 +/- 8). Infusions of
      [1-13C]palmitate, [1,1,2,3,3-2H2]glycerol, and [6,6-2H2]glucose isotope tracers
      were used to determine free fatty acid (FFA), glycerol, and glucose kinetics in
      52 of these participants (25 M and 27 W). RESULTS: There was no difference in age
      or BMI by type 1 diabetes status in either sex. Free fatty acid rate of
      appearance (FFA Ra) was higher in both sexes with type 1 diabetes compared to
      those without diabetes during stages 1 and 2. The same was seen with glycerol for
      stages 1 and 2. During stage 3 glucose rate of disappearance (Rd) was lower in
      those with type 1 diabetes among both sexes. All had sex by type 1 diabetes
      interactions with greater deficits in insulin sensitivity in women. While there
      was no sex by diabetes interaction in regards to glucose rate of appearance (Ra),
      those with type 1 diabetes had a higher glucose Ra than those without diabetes.
      CONCLUSIONS: We found that type 1 diabetes affected adipose and skeletal muscle
      insulin sensitivity to a greater extent in women than in men, perhaps
      contributing to the greater relative increase in cardiovascular risk in women
      with type 1 diabetes.

PMID- 29449139
TI  - Problems with access to dental treatment for children with epilepsy.
AB  - INTRODUCTION: Epilepsy is a common medical disorder and due to a variety of
      barriers, people with epilepsy may not have access to needed healthcare services,
      particularly based on their place of residence. OBJECTIVES: The aim of the study
      was to assess access to dental treatment in children and adolescents with
      epilepsy in Lublin Voivodeship. MATERIAL AND METHODS: Clinical and questionnaire
      examinations were performed in 107 children and young people, of both sexes, in
      the ages between 6 and 18years old from the Lublin macroregion. RESULTS: The
      majority (77.57%) of respondents regularly visited a general practitioner. Most
      of the children did not undergo regular dental checkups. Children from the large
      cities significantly more often went to a dentist compared with examinees from a
      small town and from rural areas. According to the respondents 46.73% have
      encountered barriers to dental care of their child. CONCLUSIONS: 

PMID- 29449140
TI  - Effectiveness of a multicomponent self-management intervention for adults with
      epilepsy (ZMILE study): A randomized controlled trial.
AB  - BACKGROUND: The objective of the ZMILE study was to compare the effectiveness of
      a multicomponent self-management intervention (MCI) with care as usual (CAU) in
      adult patients with epilepsy (PWE) over a six-month period. METHODS: Participants
      (PWE & relative) were randomized into intervention or CAU groups. Self-report
      questionnaires were used to measure disease-specific self-efficacy as the primary
      outcome measure and general self-efficacy, adherence, seizure severity, emotional
      functioning, quality of life, proactive coping, and side-effects of antiepileptic
      drugs (AED) as secondary outcome measures. Instruments used at baseline and
      during a six-month follow-up period were the following: disease-specific self
      efficacy (Epilepsy Self-Efficacy Scale [ESES], General Self-Efficacy Scale
      [GSES]); adherence (Medication Adherence Scale [MARS] and Medication Event
      Monitoring System [MEMS]); seizure severity (National Hospital Seizure Severity
      Scale [NHS3]); emotional well-being (Hospital Anxiety and Depression Scale
      [HADS]); quality of life (Quality of Life in Epilepsy [QOLIE-31P]); proactive
      coping (Utrecht Proactive Coping Competence [UPCC]); and side-effects of
      antiepileptic drugs [SIDAED]. Multilevel analyses were performed, and baseline
      differences were corrected by inclusion of covariates in the analyses. RESULTS:
      In total, 102 PWE were included in the study, 52 of whom were in the intervention
      group. On the SIDAED and on three of the quality of life subscales QOLIE-31P, a
      significant difference was found (p<0.05) in the intervention group. Self
      efficacy, however, showed no significant differences between the MCI and the CAU
      groups. None of the other outcome measures showed any significant difference
      between the two groups. SIGNIFICANCE: Although we found no statistically
      significant difference in the primary outcome measure, disease-specific self
      efficacy, this MCI could prove promising, since we found improvement in some
      domains of quality of life in epilepsy scale and a decrease in AED side-effects
      in the MCI group compared with the CAU group.

PMID- 29449141
TI  - Neurometabolites Alteration in the Acute Phase of Mild Traumatic Brain Injury
      (mTBI): An In Vivo Proton Magnetic Resonance Spectroscopy (1H-MRS) Study.
AB  - RATIONALE AND OBJECTIVES: Magnetic resonance spectroscopy is a noninvasive
      imaging technique that allows for reliable assessment of microscopic changes in
      brain cytoarchitecture, neuronal injuries, and neurochemical changes resultant
      from traumatic insults. We aimed to evaluate the acute alteration of
      neurometabolites in complicated and uncomplicated mild traumatic brain injury
      (mTBI) patients in comparison to control subjects using proton magnetic resonance
      spectroscopy (1H magnetic resonance spectroscopy). MATERIAL AND METHODS: Forty
      eight subjects (23 complicated mTBI [cmTBI] patients, 12 uncomplicated mTBI
      [umTBI] patients, and 13 controls) underwent magnetic resonance imaging scan with
      additional single voxel spectroscopy sequence. Magnetic resonance imaging scans
      for patients were done at an average of 10 hours (standard deviation 4.26) post
      injury. The single voxel spectroscopy adjacent to side of injury and noninjury
      regions were analysed to obtain absolute concentrations and ratio relative to
      creatine of the neurometabolites. One-way analysis of variance was performed to
      compare neurometabolite concentrations of the three groups, and a correlation
      study was done between the neurometabolite concentration and Glasgow Coma Scale.
      RESULTS: Significant difference was found in ratio of N-acetylaspartate to
      creatine (NAA/Cr + PCr) (chi2(2) = 0.22, P < .05) between the groups. The sum of
      NAA and N-acetylaspartylglutamate (NAAG) also shows significant differences in
      both the absolute concentration (NAA + NAAG) and ratio to creatine (NAA + NAAG/Cr
      + PCr) between groups (chi2(2) = 4.03, P < .05and (chi2(2) = 0.79, P < .05)). NAA
      values were lower in cmTBI and umTBI compared to control group. A moderate weak
      positive correlation were found between Glasgow Coma Scale with NAA/Cr + PCr (rho
      = 0.36, P < .05 and NAA + NAAG/Cr + PCr (rho = 0.45, P < .05)), whereas a
      moderate correlation was seen with NAA + NAAG (rho = 0.38, P < .05). CONCLUSION:
      Neurometabolite alterations were already apparent at onset of both complicated
      and uncomplicated traumatic brain injury. The ratio of NAA and NAAG has potential
      to serve as a biomarker reflecting injury severity in a quantifiable manner as it
      discriminates between the complicated and uncomplicated cases of mTBI.

PMID- 29449142
TI  - Invited Commentary: Review of "Simulation Training in Interventional Radiology"
      (Mirza and Athreaya).

PMID- 29449143
TI  - Gender Trends in Academic Radiology Publication in the United States Revisited.
AB  - RATIONALE AND OBJECTIVES: Although substantial increases in publications by
      female academic radiologists have appeared over the last several decades, it is
      possible that the rate of increase is decreasing. We examined temporal trends in
      gender composition for full-time radiology faculty, radiology residents, and
      medical students over a 46-year period. METHODS: We examined authorship gender
      trends to determine if the increases in female authorship seen since 1970 have
      been sustained in recent years and whether female radiologists continue to
      publish in proportion to their numbers in academic departments. Original articles
      for selected years in Radiology and in the American Journal of Roentgenology
      between 1970 and 2016 were examined to determine the gender of first,
      corresponding, and last authors. Generalized linear models evaluated (1) changes
      in proportions of female authorship over time and (2) associations between
      proportions of female authorship and female radiology faculty representation.
      RESULTS: While linear increases in first, corresponding, and senior authorships
      were observed for female radiologists from 1970 to 2000, the rate of increase in
      female first and corresponding authorships then changed, with the slope of the
      first author relationship decreasing from 0.81 to 0.34, corresponding to 47%
      fewer female first authors added per year. In contrast, the proportion of female
      last authorship continued to increase at the same rate. The proportion of female
      first authorship was linearly related to the proportion of female radiology
      faculty from 1970 to 2016. CONCLUSIONS: Annual increases in first author academic
      productivity of female radiologists have lessened in the past 16 years, possibly
      related to reductions in the growth of female radiology faculty and trainees. As
      mixed, compared to homogeneous gender, authorship teams are associated with more
      citations, efforts to encourage more women to pursue careers in academic
      radiology could benefit the radiology research community.

PMID- 29449144
TI  - A Dynamic Graph Cuts Method with Integrated Multiple Feature Maps for Segmenting
      Kidneys in 2D Ultrasound Images.
AB  - RATIONALE AND OBJECTIVES: Automatic segmentation of kidneys in ultrasound (US)
      images remains a challenging task because of high speckle noise, low contrast,
      and large appearance variations of kidneys in US images. Because texture features
      may improve the US image segmentation performance, we propose a novel graph cuts
      method to segment kidney in US images by integrating image intensity information
      and texture feature maps. MATERIALS AND METHODS: We develop a new graph cuts
      based method to segment kidney US images by integrating original image intensity
      information and texture feature maps extracted using Gabor filters. To handle
      large appearance variation within kidney images and improve computational
      efficiency, we build a graph of image pixels close to kidney boundary instead of
      building a graph of the whole image. To make the kidney segmentation robust to
      weak boundaries, we adopt localized regional information to measure similarity
      between image pixels for computing edge weights to build the graph of image
      pixels. The localized graph is dynamically updated and the graph cuts-based
      segmentation iteratively progresses until convergence. Our method has been
      evaluated based on kidney US images of 85 subjects. The imaging data of 20
      randomly selected subjects were used as training data to tune parameters of the
      image segmentation method, and the remaining data were used as testing data for
      validation. RESULTS: Experiment results demonstrated that the proposed method
      obtained promising segmentation results for bilateral kidneys (average Dice index
      = 0.9446, average mean distance = 2.2551, average specificity = 0.9971, average
      accuracy = 0.9919), better than other methods under comparison (P < .05, paired
      Wilcoxon rank sum tests). CONCLUSIONS: The proposed method achieved promising
      performance for segmenting kidneys in two-dimensional US images, better than
      segmentation methods built on any single channel of image information. This
      method will facilitate extraction of kidney characteristics that may predict
      important clinical outcomes such as progression of chronic kidney disease.

PMID- 29449145
TI  - Antithrombotic Therapy Following Venous Stenting: International Delphi Consensus.
AB  - OBJECTIVE/BACKGROUND: Deep venous stenting is increasingly used in the treatment
      of deep venous obstruction; however, there is currently no consensus regarding
      post-procedural antithrombotic therapy. The aim of the present study was to
      determine the most commonly used antithrombotic regimens and facilitate global
      consensus. METHODS: An electronic survey containing three clinical scenarios on
      venous stenting for non-thrombotic iliac vein lesions, acute deep vein thrombosis
      (DVT), and post-thrombotic syndrome was distributed to five societies whose
      members included vascular surgeons, interventional radiologists, and
      haematologists. The results of the initial survey (phase 1) were used to produce
      seven consensus statements, which were distributed to the respondents for
      evaluation in the second round (phase 2), along with the results of phase 1.
      Consensus was defined a priori as endorsement or rejection of a statement by >=
      67% of respondents. RESULTS: Phase 1 was completed by 106 experts, who practiced
      in 78 venous stenting centres in 28 countries. Sixty-one respondents (58%
      response rate) completed phase 2. Five of seven statements met the consensus
      criteria. Anticoagulation was the preferred treatment during the first 6-12
      months following venous stenting for a compressive iliac vein lesion. Low
      molecular weight heparin was the antithrombotic agent of choice during the first
      2-6 weeks. Lifelong anticoagulation was recommended after multiple DVTs.
      Discontinuation of anticoagulation after 6-12 months was advised following venous
      stenting for a single acute DVT. No agreement was reached regarding the role of
      long-term antiplatelet therapy. CONCLUSIONS: Consensus existed amongst
      respondents regarding anticoagulant therapy following venous stenting. At
      present, there is no consensus regarding the role of antiplatelet agents in this
      context.

PMID- 29449146
TI  - Efficacy and safety of combination therapy with SGLT2 and DPP4 inhibitors in the
      treatment of type 2 diabetes: A systematic review and meta-analysis.
AB  - BACKGROUND: This review evaluated the efficacy and safety of a combination
      therapy comprising a sodium-glucose cotransporter type 2 inhibitor (SGLT2i) and
      dipeptidyl peptidase-4 inhibitor (DPP4i) in type 2 diabetes. METHODS: A
      literature search through to May 2017 was carried out of PubMed, Embase and the
      Cochrane Central Register of Controlled Trials. Studies were eligible if they
      were randomized controlled trials (RCTs) comparing SGLT2i plus DPP4i
      (SGLT2i/DPP4i) against DPP4i+/-placebo or SGLT2i+/-placebo and published in
      English. The primary outcome was change in HbA1c from baseline. RESULTS: Eight
      RCTs comparing SGLT2i/DPP4i and DPP4i, and five RCTs comparing SGLT2i/DPP4i and
      SGLT2i, with three RCTs involving both comparisons, were included in the present
      review. SGLT2i/DPP4i resulted in a greater mean HbA1c reduction [weighted mean
      difference (WMD]): -0.62%] than did DPP4i alone, which was a much less marked
      reduction (WMD: -0.35%) than with SGLT2i alone. Also, significant differences in
      body weight loss from baseline were observed only with SGLT2i/DPP4i vs. DPP4i,
      but not vs. SGLT2i. The risk of hypoglycaemic events was low and similar between
      treatment groups. When subjects were stratified based on baseline HbA1c, any
      reduction by SGLT2i/DPP4i in relation to DPP4i was proportional to baseline HbA1c
      levels. However, compared with SGLT2i, HbA1c reductions with SGLT2i/DPP4i were
      modest regardless of baseline HbA1c. CONCLUSION: Combination therapy with SGLT2i
      and DPP4i is both efficacious and safe. In particular, a marked additional
      glucose-lowering effect is evident when SGLT2i is combined with or added to
      DPP4i, and not vice versa. However, baseline HbA1c determined the additional
      glucose-lowering effects of SGLT2i in combined treatment with DPP4i.

PMID- 29449147
TI  - Relation between HbA1c and incident cardiovascular disease over a period of 6
      years in the Hong Kong population.
AB  - AIM: The current trend on diabetes management advocates replacing the paradigm
      from a uniform to an individualized patient-centered haemoglobin A1c (HbA1c)
      target, but there is no consensus on the optimal HbA1c level. The study aimed at
      examining the association between HbA1c and the risk of cardiovascular diseases
      (CVD) for diabetic patients with different characteristics, in order to identify
      patient-centered treatment targets. METHODS: A retrospective cohort study was
      conducted on 115,782 Chinese adult primary care patients with type 2 diabetes
      mellitus (DM) but no known CVD history, who were prescribed antidiabetic
      medications in 2010-2011. The cumulative mean HbA1c over a median follow-up
      period of 5.8 years was used to evaluate the relationship between HbA1c and CVD
      incidence using Cox analysis. Subgroup analyses were conducted by stratifying
      different baseline characteristics including gender, age, smoking status,
      diabetes duration, body mass index, Charlson's comorbidity index and DM treatment
      modalities. RESULTS: For patients with a DM duration of<2years, an exponential
      relationship between HbA1c and risk of CVD was identified, suggesting that there
      was no threshold HbA1c level for CVD risk. For other diabetic patients, an HbA1c
      level of 6.8-7.2% was associated with a minimum risk for CVD and a J-shaped
      curvilinear association between HbA1c. The risk of CVD increased in patients with
      HbA1c<6.5% or >=7.5%. CONCLUSION: Among Chinese primary care patients at the
      early (<2years) disease stage, lower HbA1c targets (<6.5%) may be warranted to
      prevent CVD events whilst for all others, excessively lower HbA1c levels may not
      necessarily better and can potentially be harmful.

PMID- 29449149
TI  - Manufacturing Exosomes: A Promising Therapeutic Platform.
AB  - Extracellular vesicles, in particular the subclass exosomes, are rapidly emerging
      as a novel therapeutic platform. However, currently very few clinical validation
      studies and no clearly defined manufacturing process exist. As exosomes progress
      towards the clinic for treatment of a vast array of diseases, it is important to
      define the engineering basis for their manufacture early in the development cycle
      to ensure they can be produced cost-effectively at the appropriate scale. We
      hypothesize that transitioning to defined manufacturing platforms will increase
      consistency of the exosome product and improve their clinical advancement as a
      new therapeutic tool. We present manufacturing technologies and strategies that
      are being implemented and consider their application for the transition from
      bench-scale to clinical production of exosomes.

PMID- 29449150
TI  - [Topical tacrolimus-induced lentigines].

PMID- 29449151
TI  - Multiphase evaluation of contrast-enhanced endoscopic ultrasonography in the
      diagnosis of pancreatic solid lesions.
AB  - BACKGROUND/OBJECTIVES: Time-intensity curve (TIC) under contrast-enhanced EUS (CE
      EUS) allows continuous and quantitative evaluation of targeted area in the
      pancreas. However, TIC is not always available and the procedure is complicated.
      We aimed to propose a simplified method by evaluating multiple phases of CE-EUS
      in the diagnosis of pancreatic solid lesions. METHODS: We retrospectively
      reviewed 210 patients with pancreatic solid lesions including 142 with pancreatic
      ductal cancer (PDAC), 31 with pancreatic neuroendocrine neoplasm, 13 with solid
      pseudopapillary neoplasm and 24 with mass-forming pancreatitis who underwent CE
      EUS and achieved final diagnoses. The CE-EUS images were continuously recorded
      for 60 s, and each image at 20, 40 and 60 s was used for the evaluation. The
      images were classified into three patterns as hypoechoic, hyperechoic and
      isoechoic vascular patterns compared with the surrounding pancreas, and the
      relevance between the multiphase evaluation of CE-EUS and each disease group was
      investigated. RESULTS: In PDAC group, majority of the lesions showed hypovascular
      pattern at 20 or 40 s after injection of contrast medium following early
      enhancement. The sensitivity, specificity and accuracy of PDAC pattern in the
      differentiation of PDAC from other lesions was 83.1%, 86.8% and 84.3%,
      respectively. On histopathological analysis, significant differences were seen in
      histologic types, infiltration (INF), and neural invasion (ne) between those who
      showed PDAC pattern and those who didn't. CONCLUSIONS: Multiphase evaluation of
      CE-EUS is convenient and useful method for the differentiation of pancreatic
      solid lesions which can be alternatively used for TIC.

PMID- 29449152
TI  - Development of the Health and Weight Attitudes Scale.
AB  - OBJECTIVE: To develop and validate an instrument to assess attitudes toward
      Health at Every Size (HAES) principles. METHODS: Survey items were generated
      based on 5 HAES principles. A panel of reviewers was recruited to establish
      content validity. A convenience sample of college students in health education
      was recruited for pilot survey administration. Internal reliability was assessed
      using Cronbach alpha and test-retest reliability was assessed with Pearson
      correlation. RESULTS: Three panelists reviewed the instrument and provided
      feedback for revision. Cronbach alpha for the final instrument was .75 (n = 43)
      at pretest and .78 (n = 53) at posttest, and Pearson correlation was 0.85 (n =
      39), indicating internal consistency and test-retest reliability. CONCLUSIONS AND
      IMPLICATIONS: The instrument was determined to be both a valid and reliable
      instrument to measure HAES attitudes among college students in health education.
      Nutrition educators may find this instrument useful in other settings to assess
      HAES attitudes or as an alternative to other instruments measuring anti-fat
      attitudes.

PMID- 29449153
TI  - Exploring Grandparents' Roles in Young Children's Lifestyle Behaviors and the
      Prevention of Childhood Obesity: An Australian Perspective.
AB  - Childhood obesity remains a significant public health issue. Because lifestyle
      behaviors and weight are established early and track through life stages,
      prevention strategies must commence in the first years of life. Traditionally,
      such strategies target parents or formal child care providers. Yet grandparents
      are increasingly providing care to grandchildren and therefore have an important
      role in their eating and activity behaviors, which creates a major research gap.
      This commentary piece, focusing on the Australian context, argues that it is
      imperative and timely for obesity prevention research to include investigations
      regarding the role of grandparents in the prevention of obesity-related behaviors
      in young children.

PMID- 29449148
TI  - Therapeutic Targeting of Long Non-Coding RNAs in Cancer.
AB  - Long non-coding RNAs (lncRNAs) represent a significant population of the human
      transcriptome. Many lncRNAs exhibit cell- and/or tissue/tumor-specific
      expression, making them excellent candidates for therapeutic applications. In
      this review we discuss examples of lncRNAs that demonstrate the diversity of
      their function in various cancer types. We also discuss recent advances in
      nucleic acid drug development with a focus on oligonucleotide-based therapies as
      a novel approach to inhibit tumor progression. The increased success rates of
      nucleic acid therapeutics provide an outstanding opportunity to explore lncRNAs
      as viable therapeutic targets to combat various aspects of cancer progression.

PMID- 29449154
TI  - Lung in a Box: Ex Vivo Lung Transplantation.

PMID- 29449155
TI  - Opportunity Knocks? The Expansion of Volatile Agent Use in New Clinical Settings.

PMID- 29449157
TI  - Risk of unplanned caesarean birth in Vietnamese-born women in Victoria,
      Australia: A cross-sectional study.
AB  - BACKGROUND: Understanding the prevalence of, and factors associated with,
      caesarean birth among immigrant populations is essential for appropriate
      antenatal and postnatal resource allocation. AIMS: To compare rates of caesarean
      birth between one of the largest immigrant populations of women giving birth in
      Australia (Vietnamese-born women) with those of Australian-born women and
      investigate the odds of unplanned caesarean in these women, controlling for
      maternal characteristics, pregnancy complications and labour management factors.
      METHODS: Cross-sectional analysis of data on singleton births in Victoria,
      Australia; using data from the routinely collected Victorian Perinatal Data
      Collection. Descriptive analyses comparing maternal and obstetric factors for
      Vietnamese-born women with Australian-born women were undertaken. Using the more
      recent nine years of routinely collected data, multivariable logistic regression
      explored the association between unplanned caesarean birth and maternal country
      of birth, adjusted for maternal and obstetric factors, admission status and time
      (n=468,131). This association was also explored for 'standard primiparae'
      (n=69,039). FINDINGS: Planned and unplanned caesarean births increased
      dramatically in both Australian-born and Vietnamese-born women between 1984 and
      2007. After adjustment for obstetric and maternal factors, Vietnamese-born women
      were at greater odds of an unplanned caesarean birth compared to Australian-born
      women (adjusted odds ratio=1.32, 95% confidence interval=1.25-1.40). These
      greater odds were also found among the 'standard primiparae' (adjusted odds
      ratio=1.22, 95% confidence interval=1.07-1.40). CONCLUSION: Factors other than
      clinical risk appear to predispose Vietnamese-born women to unplanned caesarean
      birth. These may include intrapartum communication, length of residence and
      familiarity with care systems, and variations in care practices for Vietnamese
      women.

PMID- 29449156
TI  - Stochastic expression of lactate dehydrogenase A induces Escherichia coli
      persister formation.
AB  - Bacterial persisters are phenotypic variants that survive the treatment of lethal
      doses of growth-targeting antibiotics without mutations. Although the mechanism
      underlying persister formation has been studied for decades, how the persister
      phenotype is switched on and protects itself from antibiotics has been elusive.
      In this study, we focused on the lactate dehydrogenase gene (ldhA) that was
      upregulated in an Escherichia coli persister-enriched population. A survival rate
      assay using an ldhA-overexpressing strain showed that ldhA expression induced
      persister formation. To identify ldhA-mediated persister formation at the single
      cell level, time-lapse microscopy with a microfluidic device was used. Stochastic
      ldhA expression was found to induce dormancy and tolerance against high-dose
      ampicillin treatment (500 MUg/ml). To better understand the underlying mechanism,
      we investigated the relationship between ldhA-mediated persister formation and
      previously reported persister formation through aerobic metabolism repression. As
      a result, ldhA expression enhanced the proton motive force (PMF) and ATP
      synthesis. These findings suggest that ldhA-mediated persister formation pathway
      is different from previously reported persister formation via repression of
      aerobic metabolism.

PMID- 29449158
TI  - The first case of hourglass-like constriction neuropathy of a digital nerve.
AB  - Neuropathies of digital nerves are an infrequent phenomenon and their causes are
      most often mechanical. A rare cause of acute neuropathy is hourglass-like
      fascicular constriction of a nerve due to torsion. Although several cases of
      hourglass-like constriction have been described in the literature, none to our
      knowledge involved digital nerves. In this report, we present the first case of
      hourglass-like constriction of a digital nerve.

PMID- 29449159
TI  - Agenesis, functional deficiency and the common type of the flexor digitorum
      superficialis of the little finger: A meta-analysis.
AB  - Agenesis, functional deficiency and the common type of the flexor digitorum
      superficialis of the little finger are reported in the literature to be highly
      variable with significant discrepancy between clinical and cadaveric frequencies.
      The aim of this systematic review was to generate overall clinical and cadaveric
      weighted frequencies, along with ancestry-based, side-based, sex-based and
      laterality-based frequencies. A systematic literature search identified 34
      studies including 12,213 forearms/hands that met the inclusion criteria.
      Functional deficit of the FDS tendon of the little finger was significantly more
      prevalent among Iranian and Caucasian populations as compared to Indian, East
      African and Chinese populations. The weighted "clinical" frequency of functional
      absence of the FDS tendon of the little finger was 7.45%, while prevalence of the
      common type was 37.5%. The weighted "cadaveric" prevalence of muscle absence of
      the FDS-5 in the forearm was 2.5% while tendon absence in the hands was nil. An
      expanded examination technique proved to be the most accurate test for FDS
      function. In case of injury, inadequate knowledge of different connections or
      substitutions of the FDS-5 could lead to a total loss of flexion of the little
      finger. These findings support the hypothesis of a dual origin of the FDS-5 where
      the muscle portion originates in the forearm, while the tendon portion originates
      in the hand.

PMID- 29449160
TI  - Trans-tendinous flexor digitorum profundus ruptures: Diagnostic and surgical
      challenges.

PMID- 29449161
TI  - Ultrasound Training in Surgical Critical Care Fellowship: A Survey of Program
      Directors.
AB  - OBJECTIVE: Surgical critical care (SCC) fellows are expected to receive training
      in critical care ultrasound (CCUS) but training is sporadic and there is no
      standardized curriculum to guide educators. Previous studies show wide variation
      in CCUS training during fellowship across specialties but SCC has been
      underrepresented. This study was performed to assess SCC program directors' views
      regarding CCUS during fellowship training. DESIGN: Adult SCC program directors
      were surveyed regarding the role of CCUS in fellowship training. This survey
      assessed how CCUS training was performed, perceived barriers to education, and
      importance of specific studies. Survey responses were measured using a Likert
      scale ranging from 5 (strongly agree) to 1 (strongly disagree). SETTING: Web
      based survey. PARTICIPANTS: Adult Surgical Critical Care Fellowship Program
      Directors. RESULTS: A total 67 of 108 (62%) SCC program directors responded to
      the survey. Over 75% felt that CCUS during training should be a priority. Fifteen
      (24.6%) programs required a specific number of ultrasounds to be performed. Five
      programs (7.5%) provided no CCUS training at all. Over 75% felt that training in
      FAST, transthoracic echocardiography, inferior vena cava assessment, and US for
      procedures (line placement, thoracentesis, and paracentesis) were either
      important or very important but experience in transesophageal echocardiography,
      assessment for deep vein thrombosis, and pulmonary US were not important. Lack of
      time (63.8%) and trained faculty (51.2%) were the most cited barriers to
      training. CONCLUSIONS: There is a wide variation in how CCUS training is
      performed during SCC fellowship. SCC programs will need trained faculty,
      appropriate time allocation, and implementation of a standardized curriculum to
      provide consistent and high-quality CCUS education during fellowship.

PMID- 29449162
TI  - Is Video-Based Education an Effective Method in Surgical Education? A Systematic
      Review.
AB  - OBJECTIVE: Visual signs draw more attention during the learning process. Video is
      one of the most effective tool including a lot of visual cues. This systematic
      review set out to explore the influence of video in surgical education. We
      reviewed the current evidence for the video-based surgical education methods,
      discuss the advantages and disadvantages on the teaching of technical and
      nontechnical surgical skills. METHODS: This systematic review was conducted
      according to the guidelines defined in the preferred reporting items for
      systematic reviews and meta-analyses statement. The electronic databases: the
      Cochrane Library, Medline (PubMED), and ProQuest were searched from their
      inception to the 30 January 2016. The Medical Subject Headings (MeSH) terms and
      keywords used were "video," "education," and "surgery." We analyzed all full
      texts, randomised and nonrandomised clinical trials and observational studies
      including video-based education methods about any surgery. "Education" means a
      medical resident's or student's training and teaching process; not patients'
      education. We did not impose restrictions about language or publication date.
      RESULTS: A total of nine articles which met inclusion criteria were included.
      These trials enrolled 507 participants and the total number of participants per
      trial ranged from 10 to 172. Nearly all of the studies reviewed report
      significant knowledge gain from video-based education techniques. The findings of
      this systematic review provide fair to good quality studies to demonstrate
      significant gains in knowledge compared with traditional teaching. Additional
      video to simulator exercise or 3D animations has beneficial effects on training
      time, learning duration, acquisition of surgical skills, and trainee's
      satisfaction. CONCLUSION: Video-based education has potential for use in surgical
      education as trainees face significant barriers in their practice. This method is
      effective according to the recent literature. Video should be used in addition to
      standard techniques in the surgical education.

PMID- 29449163
TI  - Orthopaedic Surgery Residency Rotations and Correlation With Orthopaedic In
      Training Examination Performance.
AB  - OBJECTIVE: The Orthopaedic In-Training Examination (OITE) is administered
      annually and is used to assess medical knowledge of orthopedic surgery residents.
      Beginning in the 2013 to 2014 academic year, the ACGME expanded the postgraduate
      year (PGY)-1 curriculum from 3 to 6 months of orthopedic surgery rotations. The
      purpose of this study is to evaluate the effect of increased PGY-1 orthopedic
      surgery exposure on medical knowledge as measured by the OITE. DESIGN: From 2011
      to 2013, 24 PGY-2 residents completed 3 months of PGY-1 orthopedic training
      (Group 1). From 2014 to 2016, 24 PGY-2 residents completed 6 months of PGY-1
      orthopedic training (Group 2). The effect of an initial PGY-2 pediatrics rotation
      (Sub-group A), compared to a trauma rotation (Sub-group B) was also analyzed. The
      hypothesis of this study is that Group 2 scores higher on the OITE than Group 1.
      Raw percentage and overall percentile scores for all PGY-2 residents from 2011 to
      2016 for the pediatrics subsection, the trauma subsection, and for the overall
      OITE test in our program were recorded. Group 1 versus Group 2, and Sub-group A
      versus Sub-group B were compared (Student's t-test). SETTING: University of
      Minnesota (Institutional, Tertiary); Gillette Children's Hospital (Institutional,
      Tertiary); Regions Hospital (Institutional, Tertiary). PARTICIPANTS: 48 PGY-2
      residents from 2011 to 2016 were included in the study. RESULTS: Group 2 achieved
      higher raw and percentile scores on the OITE during their PGY-2 year than Group
      1. Sub-group B scored higher than Sub-group A on all OITE subsections and
      overall. CONCLUSIONS: This study suggests that raw percentage and percentile OITE
      scores improve with an additional 3 months of orthopedic training in the PGY-1
      year. Clinical exposure, specifically in orthopedic trauma, correlates with
      higher OITE performance in our residency program.

PMID- 29449164
TI  - Patients Taking beta-Blockers Do Not Require Increased Doses of Epinephrine for
      Anaphylaxis.
AB  - BACKGROUND: beta-Blocker use has been associated with increased anaphylaxis
      severity. OBJECTIVE: We aimed to assess for an association between beta-blocker
      use and requirement for more than 1 dose of epinephrine for anaphylaxis
      management. METHODS: We conducted a retrospective observational study of patients
      seen in our emergency department for anaphylaxis between April 2008 and January
      2015. The primary outcome measure was the number of doses of epinephrine.
      Associations with repeat epinephrine administration (>1 vs <=1 dose of
      epinephrine) and associations with any epinephrine administration (>0 vs 0 dose)
      were evaluated using logistic regression models and summarized as odds ratio (OR)
      and 95% CIs. The study was powered to detect a 10% or greater difference in need
      for repeat epinephrine administration between patients who were and were not
      taking beta-blocker medications. RESULTS: Of 789 patient visits with a documented
      medication history included in the study, 63 (8%) required more than 1
      epinephrine dose and 83 (11%) were on beta-blocker therapy. Among patients who
      required more than 1 epinephrine dose, 8 (13%) were taking a beta-blocker,
      compared with 75 patients (10%) who received 0 or 1 dose of epinephrine (OR,
      1.26; 95% CI, 0.58-2.75). Among patients who required at least 1 epinephrine
      dose, 41 (9%) were taking a beta-blocker, compared with 42 patients (12%) who
      received no epinephrine (OR, 0.73; 95% CI, 0.46-1.14). CONCLUSIONS: beta-Blocker
      use may not be clinically significant with regard to the need for epinephrine
      dosing among emergency department patients with anaphylaxis.

PMID- 29449166
TI  - Clinical characteristics and treatment outcomes of pulmonary invasive fungal
      infection among adult patients with hematological malignancy in a medical centre
      in Taiwan, 2008-2013.
AB  - BACKGROUND/PURPOSE: This study was aimed to investigate clinical characteristics
      and treatment outcomes of pulmonary invasive fungal infection (IFI) among
      patients with hematological malignancy. METHODS: All patients with hematological
      malignancy who were treated at a medical centre from 2008 to 2013 were evaluated.
      Pulmonary IFI was classified according to the European Organization for Research
      and Treatment of Cancer 2008 consensus. RESULTS: During the study period, 236
      (11.3%) of 2083 patients with hematological malignancy were diagnosed as
      pulmonary IFI, including 41 (17.4%) proven, 75 (31.8%) probable, and 120 (50.8%)
      possible cases. Among the 116 patients of proven and probable cases of pulmonary
      IFI, aspergillosis alone (n = 90, 77.6%) was predominant, followed by
      cryptococcosis alone (n = 9, 7.8%), and mucormycosis (n = 4, 3.4%). The overall
      incidence of patients with pulmonary IFI was 5.9 per 100 patient-years. The
      highest incidence (per 100 patient-year) was found in patients with acute myeloid
      leukaemia (13.7) followed by acute lymphoblastic leukaemia (11.3), and
      myelodysplastic syndrome/severe aplastic anaemia (6.7). Fourteen (5.9%) of the
      236 patients with pulmonary IFI died within 12 weeks after diagnosis of pulmonary
      IFI. Univariate analysis revealed that elderly age (>65 years) (P = 0.034), lack
      of response to anti-fungal treatment (P < 0.001), and admission to the intensive
      care unit (ICU) (P < 0.001) were predictors of poor prognosis. However, only
      admission to the ICU was an independent predictor of poor prognosis for 12-week
      mortality (P = 0.022) based on multivariate analysis. CONCLUSION: Patients with
      acute leukaemia and myelodysplastic syndrome/severe aplastic anaemia were at high
      risk of pulmonary IFI.

PMID- 29449165
TI  - Spirometry and Impulse Oscillometry in Preschool Children: Acceptability and
      Relationship to Maternal Smoking in Pregnancy.
AB  - BACKGROUND: Comparisons of the technical acceptability of spirometry and impulse
      oscillometry (IOS) and clinical correlations of the measurements have not been
      well studied in young children. There are no large studies focused on African
      American and Hispanic children. OBJECTIVES: We sought to (1) compare the
      acceptability of spirometry and IOS in 3- to 5-year-old children and (2) examine
      the relationship of maternal smoking during pregnancy to later lung function.
      METHODS: Spirometry and IOS were attempted at 4 sites from the Urban
      Environmental and Childhood Asthma Study birth cohort at ages 3, 4, and 5 years
      (472, 471, and 479 children, respectively). We measured forced expiratory flow in
      0.5 s (forced expiratory volume in 0.5 seconds [FEV0.5]) with spirometry and area
      of reactance (AX), resistance and reactance at 5 Hz (R5 and X5, respectively)
      using IOS. RESULTS: Children were more likely to achieve acceptable maneuvers
      with spirometry than with IOS at age 3 (60% vs 46%, P < .001) and 5 years (89% vs
      84%, P = .02). Performance was consistent among the 4 study sites. In children
      without recurrent wheeze, there were strong trends for higher FEV0.5 and lower R5
      and AX over time. Maternal smoking during pregnancy was associated with higher AX
      at ages 4 and 5 years (P < .01 for both years). There was no significant
      difference in FEV0.5 between children with and without in utero exposure to
      smoking. CONCLUSION: There is a higher rate of acceptable maneuvers with
      spirometry compared with IOS, but IOS may be a better indicator of peripheral
      airway function in preschool children.

PMID- 29449167
TI  - What's New in Epidemiology?
AB  - There have been a number of recent advances in the epidemiological study of male
      lower urinary tract symptoms (LUTS). Here, we have reviewed the most novel and
      important literature. Studies assessing the risk factors, natural history as well
      as impact of male LUTS are included, focussing on recent progress in the field.

PMID- 29449168
TI  - Corrigendum to "Characterisation of the sites of DNA damage-induced 53BP1
      phosphorylation catalysed by ATM and ATR" [DNA Repair 6 (2007) 1536-1544].

PMID- 29449169
TI  - Interaction of the Wnt/beta-catenin and RAS-ERK pathways involving co
      stabilization of both beta-catenin and RAS plays important roles in the
      colorectal tumorigenesis.
AB  - Cancer development is usually driven by multiple genetic and molecular
      alterations rather than by a single defect. In the human colorectal cancer (CRC),
      series of mutations of genes are involved in the different stages of
      tumorigenesis. For example, adenomatous polyposis coli (APC) and KRAS mutations
      have been known to play roles in the initiation and progression of the
      tumorigenesis, respectively. However, many studies indicate that mutations of
      these two genes, which play roles in the Wnt/beta-catenin and RAS-extra-cellular
      signal regulated kinase (ERK) pathways, respectively, cooperatively interact in
      the tumorigenesis in several different cancer types including CRC. Both Apc and
      Kras mutations critically increase number and growth rate of tumors although
      single mutation of these genes does not significantly enhance the small
      intestinal tumorigenesis of mice. Both APC and KRAS mutations even result in the
      liver metastasis with inductions of the cancer stem cells (CSCs) markers in a
      mice xenograft model. In this review, we are going to describe the history for
      interaction between the Wnt/beta-catenin and RAS/ERK pathways especially related
      with CRC, and provide the mechanical basis for the cross-talk between the two
      pathways. The highlight of the crosstalk involving the stability regulation of
      RAS protein via the Wnt/beta-catenin signaling which is directly related with the
      cellular proliferation and transformation will be discussed. Activation status of
      GSK3beta, a key enzyme involving both beta-catenin and RAS degradations, is
      regulated by the status of the Wnt/beta-catenin signaling dependent upon
      extracellular stimuli or intracellular abnormalities of the signaling components.
      The levels of both beta-catenin and RAS proteins are co-regulated by the Wnt/beta
      catenin signaling, and these proteins are overexpressed with a positive
      correlation in the tumor tissues of CRC patients. These results indicate that the
      elevation of both beta-catenin and RAS proteins is pathologically significant in
      CRC. In this review, we also will discuss further involvement of the increments
      of both beta-catenin and RAS especially mutant KRAS in the activation of CSCs and
      metastasis. Overall, the increments of beta-catenin and RAS especially mutant
      KRAS by APC loss play important roles in the cooperative tumorigenesis of CRC.

PMID- 29449170
TI  - A case of severe foetal anaemia due to anti-Kell that could not be detected by
      the weekly assessment of middle cerebral artery peak systolic velocity.

PMID- 29449171
TI  - Changes in antimicrobial susceptibility of commonly clinically significant
      isolates before and after the interventions on surgical prophylactic antibiotics
      (SPAs) in Shanghai.
AB  - Surveillances and interventions on antibiotics use have been suggested to improve
      serious drug-resistance worldwide. Since 2007, our hospital have proposed many
      measures for regulating surgical prophylactic antibiotics (carbapenems, third
      gen. cephalosporins, vancomycin, etc.) prescribing practices, like formulary
      restriction or replacement for surgical prophylactic antibiotics and timely
      feedback. To assess the impacts on drug-resistance after interventions, we
      enrolled infected patients in 2006 (pre-intervention period) and 2014 (post
      intervention period) in a tertiary hospital in Shanghai. Proportions of targeted
      pathogens were analyzed: methicillin-resistant Staphylococcus aureus (MRSA),
      vancomycin-resistant Enterococcus spp. (VRE), imipenem-resistant Escherichia coli
      (IREC), imipenem-resistant Klebsiella pneumoniae (IRKP), imipenem-resistant
      Acinetobacter baumannii (IRAB) and imipenem-resistant Pseudomonas aeruginosa
      (IRPA) isolates. Rates of them were estimated and compared between Surgical
      Department, ICU and Internal Department during two periods. The total proportions
      of targeted isolates in Surgical Department (62.44%, 2006; 64.09%, 2014) were
      more than those in ICU (46.13%, 2006; 50.99%, 2014) and in Internal Department
      (44.54%, 2006; 51.20%, 2014). Only MRSA has decreased significantly (80.48%,
      2006; 55.97%, 2014) (p<0.0001). The percentages of VRE and IREC in 3 departments
      were all <15%, and the slightest change were also both observed in Surgical
      Department (VRE: 0.76%, 2006; 2.03%, 2014) (IREC: 2.69%, 2006; 2.63%, 2014). The
      interventions on surgical prophylactic antibiotics can be effective for improving
      resistance; antimicrobial stewardship must be combined with infection control
      practices.

PMID- 29449172
TI  - pMEX01, a 70kb plasmid isolated from Escherichia coli that confers resistance to
      multiple beta-lactam antibiotics.
AB  - Multidrug-resistant microorganisms are of great concern to public health. Genetic
      mobile elements, such as plasmids, are among the most relevant mechanisms by
      which bacteria achieve this resistance. We obtained an Escherichia coli strain
      CM6, isolated from cattle presenting severe diarrheic symptoms in the State of
      Queretaro, Mexico. It was found to contain a 70kb plasmid (pMEX01) with a high
      similarity to the pHK01-like plasmids that were previously identified and
      described in Hong Kong. Analysis of the pMEX01 sequence revealed the presence of
      a blaCTX-M-14 gene, which is responsible for conferring resistance to multiple
      beta-lactam antibiotics. Several genes putatively involved in the conjugative
      transfer were also identified on the plasmid. The strain CM6 is of high
      epidemiological concern because it not only displays resistance to multiple beta
      lactam antibiotics but also to other kinds of antibiotics.

PMID- 29449173
TI  - Exopolysaccharide production from Bacillus velezensis KY471306 using statistical
      experimental design.
AB  - Exopolysaccharide (EPS) biopolymers produced by microorganisms play a crucial
      role in the environment such as health and bio-nanotechnology sectors, gelling
      agents in food and cosmetic industries in addition to bio-flocculants in the
      environmental sector as they are degradable, nontoxic. This study focuses on the
      improvement of EPS production through manipulation of different culture and
      environmental conditions using response surface methodology (RSM). Plackett
      Burman design indicated that; molasses, yeast extract and incubation temperature
      are the most effective parameters. Box-Behnken RSM indicated that; the optimum
      concentration for each parameter was 12% (w/v) for molasses, 6g/L yeast extract
      and 30 degrees C for incubation temperature. The most potent bacterial isolate
      was identified as Bacillus velezensis KY498625. After production, EPS was
      extracted, purified using DEAE-cellulose, identified using Fourier transform
      infrared (FTIR), gel permeation chromatography (GPC) and gas chromatography-mass
      spectroscopy (GC-MS). The result indicated that; it has molecular weight
      1.14*105D consisting of glucose, mannose and galactose.

PMID- 29449174
TI  - Survival of Salmonella spp. in minced meat packaged under vacuum and modified
      atmosphere.
AB  - The effect of different modified atmosphere packaging regimes on the behavior of
      Salmonella spp. on minced meat was studied. Minced meat was experimentally
      contaminated with a Salmonella spp. cocktail (S. Enteritidis, S. Typhimurium, S.
      Infantis and S. Arizonae), packaged under vacuum or modified atmosphere with
      initial headspaces containing 20%O2/50%CO2/30%N2 and 20%O2/30%CO2/50%N2) and
      stored at 3+/-1 degrees C for 12 days. Samples were analyzed for Salmonella spp.,
      viable and lactic acid bacteria count every third day. Salmonella spp. counts
      decreased during storage in all packaging types, with reductions of about
      1.5logCFU/g. A significant difference (p<0.01) was noted between Salmonella spp.
      counts in meat packaged in vacuum and modified atmospheres, although there was no
      significant difference in Salmonella spp. count between meat packaged in 50%CO2,
      and meat packaged in 30%CO2. At the end of the study, there were significant
      differences (p<0.01; p<0.05) in total viable and lactic acid bacterial counts
      between meat packaged in vacuum and modified atmosphere, and the lowest counts
      were noted in meat packaged in modified atmosphere with 50%CO2.

PMID- 29449175
TI  - Study of pandrug and heavy metal resistance among E. coli from anthropogenically
      influenced Delhi stretch of river Yamuna.
AB  - Escalating burden of antibiotic resistance that has reached new heights present a
      grave concern to mankind. As the problem is no longer confined to clinics, we
      hereby report identification of a pandrug resistant Escherichia coli isolate from
      heavily polluted Delhi stretch of river Yamuna, India. E. coli MRC11 was found
      sensitive only to tobramycin against 21 antibiotics tested, with minimum
      inhibitory concentration values >256MUg/mL for amoxicillin, carbenicillin,
      aztreonam, ceftazidime and cefotaxime. Addition of certain heavy metals at higher
      concentrations were ineffective in increasing susceptibility of E. coli MRC11 to
      antibiotics. Withstanding sub-optimal concentration of cefotaxime (10MUg/mL) and
      mercuric chloride (2MUg/mL), and also resistance to their combinatorial use,
      indicates better adaptability in heavily polluted environment through clustering
      and expression of resistance genes. Interestingly, E. coli MRC11 harbours two
      different variants of blaTEM (blaTEM-116 and blaTEM-1 with and without extended
      spectrum activity, respectively), in addition to mer operon (merB, merP and merT)
      genes. Studies employing conjugation, confirmed localization of blaTEM-116, merP
      and merT genes on the conjugative plasmid. Understanding potentialities of such
      isolates will help in determining risk factors attributing pandrug resistance and
      strengthening strategic development of new and effective antimicrobial agents.

PMID- 29449176
TI  - Rubber gloves biodegradation by a consortium, mixed culture and pure culture
      isolated from soil samples.
AB  - An increasing production of natural rubber (NR) products has led to major
      challenges in waste management. In this study, the degradation of rubber latex
      gloves in a mineral salt medium (MSM) using a bacterial consortium, a mixed
      culture of the selected bacteria and a pure culture were studied. The highest 18%
      weight loss of the rubber gloves were detected after incubated with the mixed
      culture. The increased viable cell counts over incubation time indicated that
      cells used rubber gloves as sole carbon source leading to the degradation of the
      polymer. The growth behavior of NR-degrading bacteria on the latex gloves surface
      was investigated using the scanning electron microscope (SEM). The occurrence of
      the aldehyde groups in the degradation products was observed by Fourier Transform
      Infrared Spectroscopy analysis. Rhodococcus pyridinivorans strain F5 gave the
      highest weight loss of rubber gloves among the isolated strain and posses latex
      clearing protein encoded by lcp gene. The mixed culture of the selected strains
      showed the potential in degrading rubber within 30 days and is considered to be
      used efficiently for rubber product degradation. This is the first report to
      demonstrate a strong ability to degrade rubber by Rhodococcus pyridinivorans.

PMID- 29449178
TI  - Comment on: a pilot study of primary care physicians' attitude to weight loss
      surgery in England: are the young more prejudiced?

PMID- 29449177
TI  - Cloning and expression of an endoglucanase gene from the thermotolerant fungus
      Aspergillus fumigatus DBiNU-1 in Kluyveromyces lactis.
AB  - An intronless endoglucanase from thermotolerant Aspergillus fumigatus DBINU-1 was
      cloned, characterized and expressed in the yeast Kluyveromyces lactis. The full
      length open reading frame of the endoglucanase gene from A. fumigatus DBiNU-1,
      designated Cel7, was 1383 nucleotides in length and encoded a protein of 460
      amino acid residues. The predicted molecular weight and the isoelectric point of
      the A. fumigatus Cel7 gene product were 48.19kDa and 5.03, respectively. A
      catalytic domain in the N-terminal region and a fungal type cellulose-binding
      domain/module in the C-terminal region were detected in the predicted polypeptide
      sequences. Furthermore, a signal peptide with 20 amino acid residues at the N
      terminus was also detected in the deduced amino acid sequences of the
      endoglucanase from A. fumigatus DBiNU-1. The endoglucanase from A. fumigatus
      DBiNU-1 was successfully expressed in K. lactis, and the purified recombinant
      enzyme exhibited its maximum activity at pH 5.0 and 60 degrees C. The enzyme was
      very stable in a pH range from 4.0 to 8.0 and a temperature range from 30 to 60
      degrees C. These features make it suitable for application in the paper, biofuel,
      and other chemical production industries that use cellulosic materials.

PMID- 29449179
TI  - The end of family therapy for self-harm, or a new beginning?

PMID- 29449180
TI  - Effectiveness of systemic family therapy versus treatment as usual for young
      people after self-harm: a pragmatic, phase 3, multicentre, randomised controlled
      trial.
AB  - BACKGROUND: Self-harm in adolescents is common and repetition occurs in a high
      proportion of these cases. Scarce evidence exists for effectiveness of
      interventions to reduce self-harm. METHODS: This pragmatic, multicentre,
      randomised, controlled trial of family therapy versus treatment as usual was done
      at 40 UK Child and Adolescent Mental Health Services (CAMHS) centres. We
      recruited young people aged 11-17 years who had self-harmed at least twice and
      presented to CAMHS after self-harm. Participants were randomly assigned (1:1) to
      receive manualised family therapy delivered by trained and supervised family
      therapists or treatment as usual by local CAMHS. Participants and therapists were
      aware of treatment allocation; researchers were masked. The primary outcome was
      hospital attendance for repetition of self-harm in the 18 months after group
      assignment. Primary and safety analyses were done in the intention-to-treat
      population. The trial is registered at the ISRCTN registry, number
      ISRCTN59793150. FINDINGS: Between Nov 23, 2009, and Dec 31, 2013, 3554 young
      people were screened and 832 eligible young people consented to participation and
      were randomly assigned to receive family therapy (n=415) or treatment as usual
      (n=417). Primary outcome data were available for 795 (96%) participants. Numbers
      of hospital attendances for repeat self-harm events were not significantly
      different between the groups (118 [28%] in the family therapy group vs 103 [25%]
      in the treatment as usual group; hazard ratio 1.14 [95% CI 0.87-1.49] p=0.33).
      Similar numbers of adverse events occurred in both groups (787 in the family
      therapy group vs 847 in the treatment as usual group). INTERPRETATION: For
      adolescents referred to CAMHS after self-harm, having self-harmed at least once
      before, our family therapy intervention conferred no benefits over treatment as
      usual in reducing subsequent hospital attendance for self-harm. Clinicians are
      therefore still unable to recommend a clear, evidence-based intervention to
      reduce repeated self-harm in adolescents. FUNDING: National Institute for Health
      Research Health Technology Assessment programme.

PMID- 29449181
TI  - Roux en Y gastric bypass hypoglycemia resolves with gastric feeding or reversal:
      Confirming a non-pancreatic etiology.
AB  - OBJECTIVE: Postprandial hypoglycemia is an infrequent but disabling complication
      of Roux-en-Y gastric bypass (RYGB) surgery. Controversy still exists as to
      whether the postprandial hyperinsulinemia observed is due to inherent changes in
      pancreatic beta-cell mass or function or to reversible alterations caused by RYGB
      anatomy. We aimed to determine if gastric feeding or reversal of RYGB would
      normalize postprandial glucose and hormone excursions in patients with
      symptomatic hypoglycemia. METHODS: We completed a prospective study of six
      patients with severe symptomatic RYGB hypoglycemia who underwent RYGB reversal.
      An additional subject without hypoglycemia who underwent RYGB reversal was also
      studied prospectively. Mixed meal tolerance testing (MTT) was done orally (RYGB
      anatomy), via gastrostomy tube in the excluded stomach in the setting of RYGB,
      and several months after RYGB reversal. RESULTS: All subjects reported
      symptomatic improvement of hypoglycemia after reversal of RYGB. Weight gain after
      reversal was moderate and variable. Postprandial glucose, insulin, and GLP-1
      excursions were significantly diminished with gastric feeding and after reversal.
      Insulin secretion changed proportional to glucose levels and insulin clearance
      increased after reversal. Glucagon/insulin ratios were similar throughout study.
      We further compared the impact of modified sleeve gastrectomy reversal surgery to
      those with restoration of complete stomach and found no significant differences
      in weight regain or in postprandial glucose or hormone levels. CONCLUSIONS:
      Reversal of RYGB is an effective treatment option for severe postprandial
      hypoglycemia. The pathophysiology of this disorder is primarily due to RYGB
      anatomy resulting in altered glucose, gut, and pancreatic hormone levels and
      decreased insulin clearance, rather than inherent beta-cell hyperplasia or
      hyperfunction.

PMID- 29449182
TI  - Early-onset generalized dystonia starting in the lower extremities in a patient
      with a novel ANO3 variant.

PMID- 29449183
TI  - Altered resting-state voxel-level whole-brain functional connectivity in
      depressed Parkinson's disease.
AB  - BACKGROUND: Depression is one of the most common non-motor symptoms in
      Parkinson's disease (PD), but its pathogenesis is still not very clear. Recently,
      degree centrality, a voxel-level whole-brain functional connectivity (FC)
      analysis of resting-state functional magnetic resonance imaging, has provided the
      most promising way to explore the neural network mechanisms underlying depressed
      PD. METHODS: Degree centrality, voxel-wise image and clinical symptoms
      correlation and secondary seed-based FC analyses were performed in twenty-seven
      drug-naive, early stage depressed PD patients, 27 non-depressed PD patients and
      27 healthy controls (HCs) to reveal voxel-level whole-brain FC changes in
      depressed PD. RESULTS: Compared with the HCs, depressed PD and non-depressed PD
      patients shared similar brain degree centrality abnormalities mainly in the basal
      ganglia, insular cortex, motor cortices, default mode network, prefrontal gyrus
      and the cerebellum. However, compared with non-depressed PD, depressed PD showed
      degree centrality abnormalities in the right middle prefrontal gyrus, anterior
      cingulate cortices, supplementary motor cortices and cerebellum lobule VI. The
      right middle prefrontal gyrus degree centrality abnormalities were correlated
      with the clinical depression severity, and using it as a seed, a secondary seed
      based FC analysis further revealed the FC changes in the anterior cingulate
      cortices and the cerebellum lobule VI. CONCLUSIONS: Our findings revealed that
      dysfunction in extensive brain areas were involved in depressed PD, and among
      these regions, the right middle prefrontal gyrus, anterior cingulate cortices and
      the cerebellum may pose as pathogenesis hubs underlying depressed PD.

PMID- 29449184
TI  - Relation of overactive bladder with motor symptoms and dopamine transporter
      imaging in drug-naive Parkinson's disease.
AB  - OBJECTIVES: The aim of the present study was to determine the relation of urinary
      dysfunction with motor symptoms and nigrostriatal neuron loss in drug-naive
      patients with Parkinson's disease (PD). We therefore examined the relation of
      overactive bladder (OAB) symptoms with motor symptoms and striatal dopamine
      transporter (DAT) binding measured by [123-Iodine]-fluoropropyl-2beta
      carbomethoxy-3beta-(4-iodophenylnortropane) dopamine transporter single-photon
      emission computed tomography (123I-FP-CIT SPECT). PATIENTS AND METHODS: Thirty
      one untreated PD patients (12 men and 19 women with a mean age of 71.2 +/- 6.7
      years) were included in this study. Patients were evaluated with overactive
      bladder symptom score (OABSS) and divided into an OAB group and Non-OAB group.
      They underwent clinical assessments and 123I-FP-CIT SPECT imaging. Motor symptoms
      were assessed using Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS:
      The results showed that UPDRS motor score (p = 0.01) and akinetic-rigid score (p
      = 0.002) were higher and that striatal DAT availability (p = 0.01) was lower in
      the OAB group than in the Non-OAB group. However, tremor score, age, and duration
      of PD showed no significant differences between the OAB group and Non-OAB group.
      CONCLUSIONS: Urinary dysfunction in untreated PD is related with increase in
      motor symptoms (especially bradykinesia and axial symptoms) and reduction of
      striatal DAT availability.

PMID- 29449185
TI  - Association of coffee consumption and non-motor symptoms in drug-naive, early
      stage Parkinson's disease.
AB  - OBJECTIVE: Coffee consumption has an inverse association with the risk of
      Parkinson's disease (PD). The aim of this study was to investigate the
      association between coffee consumption and non-motor symptoms (NMSs) in patients
      with PD. METHODS: In this cross-sectional study, we included 196 early-stage,
      treatment-naive PD patients. Coffee consumption history was obtained via semi
      structured interviews. NMSs were assessed using the Non-Motor Symptom assessment
      scale (NMSS). RESULTS: Of the 196 patients with PD, 136 (69.3%) were categorized
      as coffee drinkers and 60 (30.6%) were non-drinkers. Coffee drinkers were
      younger, predominantly male, were younger in age at symptom onset, had lower
      Unified Parkinson's Disease Rating Scale motor and Beck Depression Inventory
      scores, and higher Mini-Mental State Examination scores than non-coffee drinkers.
      After adjustment, coffee drinking was significantly inversely associated with the
      prevalence of lack of motivation, anhedonia, and lack of pleasure, which were
      less frequent in coffee drinkers. Total NMSS scores were lower in coffee drinkers
      than in non-drinkers (p = 0.047). In particular, coffee drinking was
      significantly associated with a reduced severity of the mood/cognition domain of
      NMSS (p = 0.003). After correcting for multiple testing, there were no
      significant differences in the prevalence of NMSs, but there were significant
      differences in the severity of NMSs between coffee drinkers and non-drinkers.
      CONCLUSION: There is a negative association between coffee consumption and the
      severity of the mood/cognition domain of NMSS in patients with PD. Clinicians
      should consider the history of coffee consumption in the assessment of NMSs in
      PD.

PMID- 29449186
TI  - The reorganization of functional architecture in the early-stages of Parkinson's
      disease.
AB  - INTRODUCTION: The study aim was to identify longitudinal abnormalities of
      functional connectivity and its relation with motor disability in early to
      moderately advanced stages of Parkinson's disease patients. METHODS: 3.0T
      structural and resting-state functional MRI was performed in healthy subjects (n
      = 16) and Parkinson's disease patients (n = 16) with mean disease duration of 2.2
      +/- 1.2 years at baseline with a clinical follow-up of 1.5 +/- 0.3 years. Resting
      state fMRI analysis included region-to-region connectivity in correlation with
      UPDRS-III scores and computation of Global Efficiency and Degree Centrality.
      RESULTS: At baseline, patients' connectivity increased between the cerebellum and
      somatomotor network, and decreased between motor regions (Rolandic operculum,
      precentral gyrus, supplementary motor area, postcentral gyrus) and cingulate
      connectivity. At 1.5 years follow-up, connectivity remained altered in the same
      regions identified at baseline. The cerebellum showed additional
      hyperconnectivity within itself and to the caudate nucleus, thalamus and amygdala
      compared to controls. These differences correlated with UPDRS-III scores. Seed
      based connectivity revealed increased involvement of the default mode network
      with precentral gyrus in patients at follow-up investigation. CONCLUSION: Resting
      state fMRI identified marked disturbances of the overall architecture of
      connectivity in Parkinson's disease. The noted alterations in cortical motor
      areas were associated with cerebellar hyperconnectivity in early to moderately
      advanced stages of Parkinson's disease suggesting ongoing attempts of recovery
      and compensatory mechanism for affected functions. The potential to identify
      connectivity alterations in regions related to both motor and attentional
      functions requires further evaluation as an objective marker to monitor disease
      progression, and medical, as well as surgical interventions.

PMID- 29449187
TI  - Cortical atrophy patterns in early Parkinson's disease patients using
      hierarchical cluster analysis.
AB  - INTRODUCTION: Cortical brain atrophy detectable with MRI in non-demented advanced
      Parkinson's disease (PD) is well characterized, but its presence in early disease
      stages is still under debate. We aimed to investigate cortical atrophy patterns
      in a large sample of early untreated PD patients using a hypothesis-free data
      driven approach. METHODS: Seventy-seven de novo PD patients and 50 controls from
      the Parkinson's Progression Marker Initiative database with T1-weighted images in
      a 3-tesla Siemens scanner were included in this study. Mean cortical thickness
      was extracted from 360 cortical areas defined by the Human Connectome Project
      Multi-Modal Parcellation version 1.0, and a hierarchical cluster analysis was
      performed using Ward's linkage method. A general linear model with cortical
      thickness data was then used to compare clustering groups using FreeSurfer
      software. RESULTS: We identified two patterns of cortical atrophy. Compared with
      controls, patients grouped in pattern 1 (n = 33) were characterized by cortical
      thinning in bilateral orbitofrontal, anterior cingulate, and lateral and medial
      anterior temporal gyri. Patients in pattern 2 (n = 44) showed cortical thinning
      in bilateral occipital gyrus, cuneus, superior parietal gyrus, and left
      postcentral gyrus, and they showed neuropsychological impairment in memory and
      other cognitive domains. CONCLUSIONS: Even in the early stages of PD, there is
      evidence of cortical brain atrophy. Neuroimaging clustering analysis is able to
      detect two subgroups of cortical thinning, one with mainly anterior atrophy, and
      the other with posterior predominance and worse cognitive performance.

PMID- 29449188
TI  - Novel homozygous variants in ATCAY, MCOLN1, and SACS in complex neurological
      disorders.
AB  - BACKGROUND: Neurological disorders comprise a large group of clinically and
      genetically heterogeneous disorders, many of which have a genetic cause. In
      addition to a detailed neurological examination, exome sequencing is being
      increasingly used as a complementary diagnostic tool to identify the underlying
      genetic cause in patients with unclear, supposedly genetically determined
      disorders. OBJECTIVE: To identify the genetic cause of a complex movement
      disorder in five consanguineous Pakistani families. METHODS: We included five
      consanguineous Pakistani families with complex recessively inherited movement
      disorders. Clinical investigation including videotaping was carried out in a
      total of 59 family members (4-21 per family) and MRI in six patients. Exome
      sequencing was performed in 4-5 family members per pedigree to explore the
      underlying genetic cause. RESULTS: Patients presented a wide spectrum of
      neurological symptoms including ataxia and/or dystonia. We identified three novel
      homozygous, segregating variants in ATCAY (p.Pro200Profs*20), MCOLN1
      (p.Ile184Thr), and SACS (p.Asn3040Lysfs*4) in three of the families. Thus, we
      were able to identify the likely cause of the disease in a considerable number of
      families (60%) with the relatively simple and nowadays widely available method of
      exome sequencing. Of note, close collaboration of neurologists and geneticists
      was instrumental for proper data interpretation. CONCLUSIONS: We expand the
      phenotypic, genotypic, and ethnical spectrum of mutations in these genes. Our
      findings alert neurologists that rare genetic causes should be considered in
      complex phenotypes regardless of ethnicity.

PMID- 29449190
TI  - Adjuvant therapy for women with high-risk endometrial carcinoma.

PMID- 29449191
TI  - BMI and outcomes in melanoma: more evidence for the obesity paradox.

PMID- 29449189
TI  - Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk
      endometrial cancer (PORTEC-3): final results of an international, open-label,
      multicentre, randomised, phase 3 trial.
AB  - BACKGROUND: Although women with endometrial cancer generally have a favourable
      prognosis, those with high-risk disease features are at increased risk of
      recurrence. The PORTEC-3 trial was initiated to investigate the benefit of
      adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus
      pelvic radiotherapy alone for women with high-risk endometrial cancer. METHODS:
      PORTEC-3 was an open-label, international, randomised, phase 3 trial involving
      103 centres in six clinical trials collaborating in the Gynaecological Cancer
      Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage
      I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular
      space invasion (or both), endometrioid-type stage II or III, or stage I to III
      with serous or clear cell histology. Women were randomly assigned (1:1) to
      receive radiotherapy alone (48.6 Gy in 1.8 Gy fractions given on 5 days per week)
      or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m2
      given during radiotherapy, followed by four cycles of carboplatin AUC5 and
      paclitaxel 175 mg/m2) using a biased-coin minimisation procedure with
      stratification for participating centre, lymphadenectomy, stage of cancer, and
      histological type. The co-primary endpoints were overall survival and failure
      free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression
      analysis for final analysis by intention to treat and adjusted for stratification
      factors. The study was closed on Dec 20, 2013, after achieving complete accrual;
      follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080,
      and ClinicalTrials.gov, number NCT00411138. RESULTS: 686 women were enrolled
      between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in
      the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were
      assigned to radiotherapy. Median follow-up was 60.2 months (IQR 48.1-73.1). 5
      year overall survival was 81.8% (95% CI 77.5-86.2) with chemoradiotherapy versus
      76.7% (72.1-81.6) with radiotherapy (adjusted hazard ratio [HR] 0.76, 95% CI 0.54
      1.06; p=0.11); 5-year failure-free survival was 75.5% (95% CI 70.3-79.9) versus
      68.6% (63.1-73.4; HR 0.71, 95% CI 0.53-0.95; p=0.022). Grade 3 or worse adverse
      events during treatment occurred in 198 (60%) of 330 who received
      chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy
      (p<0.0001). Neuropathy (grade 2 or worse) persisted significantly more often
      after chemoradiotherapy than after radiotherapy (20 [8%] women vs one [1%] at 3
      years; p<0.0001). Most deaths were due to endometrial cancer; in four patients
      (two in each group), the cause of death was uncertain. One death in the
      radiotherapy group was due to either disease progression or late treatment
      complications; three deaths (two in the chemoradiotherapy group and one in the
      radiotherapy group) were due to either intercurrent disease or late treatment
      related toxicity. INTERPRETATION: Adjuvant chemotherapy given during and after
      radiotherapy for high-risk endometrial cancer did not improve 5-year overall
      survival, although it did increase failure-free survival. Women with high-risk
      endometrial cancer should be individually counselled about this combined
      treatment. Continued follow-up is needed to evaluate long-term survival. FUNDING:
      Dutch Cancer Society, Cancer Research UK, National Health and Medical Research
      Council Project Grant and Cancer Australia, L'Agenzia Italiana del Farmaco, and
      Canadian Cancer Society Research Institute.

PMID- 29449192
TI  - Association of body-mass index and outcomes in patients with metastatic melanoma
      treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective,
      multicohort analysis.
AB  - BACKGROUND: Obesity has been linked to increased mortality in several cancer
      types; however, the relation between obesity and survival outcomes in metastatic
      melanoma is unknown. The aim of this study was to examine the association between
      body-mass index (BMI) and progression-free survival or overall survival in
      patients with metastatic melanoma who received targeted therapy, immunotherapy,
      or chemotherapy. METHODS: This retrospective study analysed independent cohorts
      of patients with metastatic melanoma assigned to treatment with targeted therapy,
      immunotherapy, or chemotherapy in randomised clinical trials and one
      retrospective study of patients treated with immunotherapy. Patients were
      classified according to BMI, following the WHO definitions, as underweight,
      normal, overweight, or obese. Patients without BMI and underweight patients were
      excluded. The primary outcomes were the associations between BMI and progression
      free survival or overall survival, stratified by treatment type and sex. We did
      multivariable analyses in the independent cohorts, and combined adjusted hazard
      ratios in a mixed-effects meta-analysis to provide a precise estimate of the
      association between BMI and survival outcomes; heterogeneity was assessed with
      meta-regression analyses. Analyses were done on the predefined intention-to-treat
      population in the randomised controlled trials and on all patients included in
      the retrospective study. FINDINGS: The six cohorts consisted of a total of 2046
      patients with metastatic melanoma treated with targeted therapy, immunotherapy,
      or chemotherapy between Aug 8, 2006, and Jan 15, 2016. 1918 patients were
      included in the analysis. Two cohorts containing patients from randomised
      controlled trials treated with targeted therapy (dabrafenib plus trametinib
      [n=599] and vemurafenib plus cobimetinib [n=240]), two cohorts containing
      patients treated with immunotherapy (one randomised controlled trial of
      ipilimumab plus dacarbazine [n=207] and a retrospective cohort treated with
      pembrolizumab, nivolumab, or atezolizumab [n=331]), and two cohorts containing
      patients treated with chemotherapy (two randomised controlled trials of
      dacarbazine [n=320 and n=221]) were classified according to BMI as normal (694
      [36%] patients), overweight (711 [37%]), or obese (513 [27%]). In the pooled
      analysis, obesity, compared with normal BMI, was associated with improved
      survival in patients with metastatic melanoma (average adjusted hazard ratio [HR]
      0.77 [95% CI 0.66-0.90] for progression-free survival and 0.74 [0.58-0.95] for
      overall survival). The survival benefit associated with obesity was restricted to
      patients treated with targeted therapy (HR 0.72 [0.57-0.91] for progression-free
      survival and 0.60 [0.45-0.79] for overall survival) and immunotherapy (HR 0.75
      [0.56-1.00] and 0.64 [0.47-0.86]). No associations were observed with
      chemotherapy (HR 0.87 [0.65-1.17, pinteraction=0.61] for progression-free
      survival and 1.03 [0.80-1.34, pinteraction=0.01] for overall survival). The
      association of BMI with overall survival for patients treated with targeted and
      immune therapies differed by sex, with inverse associations in men (HR 0.53 [0.40
      0.70]), but no associations observed in women (HR 0.85 [0.61-1.18,
      pinteraction=0.03]). INTERPRETATION: Our results suggest that in patients with
      metastatic melanoma, obesity is associated with improved progression-free
      survival and overall survival compared with those outcomes in patients with
      normal BMI, and that this association is mainly seen in male patients treated
      with targeted or immune therapy. These results have implications for the design
      of future clinical trials for patients with metastatic melanoma and the magnitude
      of the benefit found supports further investigation of the underlying mechanism
      of these associations. FUNDING: ASCO/CCF Young Investigator Award, ASCO/CCF
      Career Development Award, MD Anderson Cancer Center (MDACC) Melanoma Moonshot
      Program, MDACC Melanoma SPORE, and the Dr Miriam and Sheldon G Adelson Medical
      Research Foundation.

PMID- 29449193
TI  - Phase I Trial of Intrathecal Mesenchymal Stem Cell-derived Neural Progenitors in
      Progressive Multiple Sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is an immune-mediated demyelinating disease
      of the central nervous system and is one of the leading causes of disability in
      young adults. Cell therapy is emerging as a therapeutic strategy to promote
      repair and regeneration in patients with disability associated with progressive
      MS. METHODS: We conducted a phase I open-label clinical trial investigating the
      safety and tolerability of autologous bone marrow mesenchymal stem cell-derived
      neural progenitor (MSC-NP) treatment in 20 patients with progressive MS. MSC-NPs
      were administered intrathecally (IT) in three separate doses of up to 1 * 107
      cells per dose, spaced three months apart. The primary endpoint was to assess
      safety and tolerability of the treatment. Expanded disability status scale
      (EDSS), timed 25-ft walk (T25FW), muscle strength, and urodynamic testing were
      used to evaluate treatment response. This trial is registered with
      ClinicalTrials.gov, number NCT01933802. FINDINGS: IT MSC-NP treatment was safe
      and well tolerated. The 20 enrolled subjects completed all 60 planned treatments
      without serious adverse effects. Minor adverse events included transient fever
      and mild headaches usually resolving in <24 h. Post-treatment disability score
      analysis demonstrated improved median EDSS suggesting possible efficacy. Positive
      trends were more frequently observed in the subset of SPMS patients and in
      ambulatory subjects (EDSS <= 6.5). In addition, 70% and 50% of the subjects
      demonstrated improved muscle strength and bladder function, respectively,
      following IT MSC-NP treatment. INTERPRETATION: The possible reversal of
      disability that was observed in a subset of patients warrants a larger phase II
      placebo-controlled study to establish efficacy of IT MSC-NP treatment in patients
      with MS. FUNDING SOURCE: The Damial Foundation.

PMID- 29449196
TI  - Clinical predictors of successful vaginal myomectomy for prolapsed pedunculated
      uterine leiomyoma
AB  - Objective: Uterine leiomyomas are the most common pelvic tumor in women. The
      calculated prevalence of prolapsed pedunculated leiomyoma was 2.5% in patients
      who underwent surgery. Although vaginal removal is safe and effective,
      hysterectomy demand is questionable. We aimed to analyze the association between
      patient characteristics, clinical features of prolapsed pedunculated submucosal
      leiomyoma, and the probability of successful vaginal myomectomy. Material and
      Methods: This study was conducted in 35 women who presented with prolapsed
      pedunculated uterine leiomyoma. Patients were grouped according to the treatment
      procedure, either vaginal myomectomy or hysterectomy. Results: Hysterectomy was
      performed in 14 patients and vaginal myomectomy was performed in 21 women. The
      mean ages and menopausal status were similar. Parity was higher in the
      hysterectomy group (p=0.02). The preoperative hematocrit value of patients
      undergoing vaginal myomectomy was significantly lower (p=0.04). There was no
      significant difference between the groups regarding the largest leiomyoma
      diameter. However, the median calculated leiomyoma volume was lower in the
      vaginal myomectomy group (p=0.04). None of the variables were independently
      associated with successful vaginal myomectomy on multivariable logistic
      regression analysis. Conclusion: The feasibility and choice of vaginal myomectomy
      is associated with low parity, absence of coexisting leiomyoma, high volume of
      leiomyoma estimated via ultrasound measurement, and severe anemia.

PMID- 29449194
TI  - Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous
      Narcolepsy Type 1: Large-scale Study of Antibody Profiling.
AB  - BACKGROUND: Neuropathological findings support an autoimmune etiology as an
      underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy
      type 1 (narcolepsy with cataplexy; sNT1) as well as in Pandemrix influenza
      vaccine-induced narcolepsy type 1 (Pdmx-NT1). The precise molecular target or
      antigens for the immune response have, however, remained elusive. METHODS: Here
      we have performed a comprehensive antigenic repertoire analysis of sera using the
      next-generation phage display method - mimotope variation analysis (MVA). Samples
      from 64 children and adolescents were analyzed: 10 with Pdmx-NT1, 6 with sNT1, 16
      Pandemrix-vaccinated, 16 H1N1 infected, and 16 unvaccinated healthy individuals.
      The diagnosis of NT1 was defined by the American Academy of Sleep Medicine
      international criteria of sleep disorders v3. FINDINGS: Our data showed that
      although the immunoprofiles toward vaccination were generally similar in study
      groups, there were also striking differences in immunoprofiles between sNT1 and
      Pdmx-NT1 groups as compared with controls. Prominent immune response was observed
      to a peptide epitope derived from prostaglandin D2 receptor (DP1), as well as
      peptides homologous to B cell lymphoma 6 protein. Further validation confirmed
      that these can act as true antigenic targets in discriminating NT1 diseased along
      with a novel epitope of hemagglutinin of H1N1 to delineate exposure to H1N1.
      INTERPRETATION: We propose that DP1 is a novel molecular target of autoimmune
      response and presents a potential diagnostic biomarker for NT1. DP1 is involved
      in the regulation of non-rapid eye movement (NREM) sleep and thus alterations in
      its functions could contribute to the disturbed sleep regulation in NT1 that
      warrants further studies. Together our results also show that MVA is a helpful
      method for finding novel peptide antigens to classify human autoimmune diseases,
      possibly facilitating the design of better therapies.

PMID- 29449195
TI  - Neutrophil Microvesicles from Healthy Control and Rheumatoid Arthritis Patients
      Prevent the Inflammatory Activation of Macrophages.
AB  - Microvesicles (MVs) are emerging as a novel means to enact cell-to-cell
      communication in inflammation. Here, we aimed to ascertain the ability of
      neutrophil-derived MVs to modulate target cell behaviour, the focus being the
      macrophage. MVs were generated in response to tumour necrosis factor-alpha, from
      healthy control neutrophils or those from rheumatoid arthritis patients. MVs were
      used to stimulate human monocyte-derived macrophages in vitro, or administered
      intra-articularly in the K/BxN mouse model of arthritis. A macrophage/fibroblast
      like synoviocyte co-culture system was used to study the effects of vesicles on
      the crosstalk between these cells. We demonstrate a direct role for
      phosphatidylserine and annexin-A1 exposed by the MVs to counteract classical
      activation of the macrophages, and promote the release of transforming growth
      factor-beta, respectively. Classically-activated macrophages exposed to
      neutrophil MVs no longer activated fibroblast-like synoviocytes in subsequent co
      culture settings. Finally, intra-articular administration of neutrophil MVs from
      rheumatoid arthritis patients in arthritic mice affected the phenotype of joint
      macrophages. Altogether these data, with the identification of specific MV
      determinants, open new opportunities to modulate on-going inflammation in the
      synovia - mainly by affecting macrophage polarization and potentially also
      fibroblast-like synoviocytes - through the delivery of autologous or heterologous
      MVs produced from neutrophils.

PMID- 29449197
TI  - Letter from a young female physician, Candidate

PMID- 29449198
TI  - A Rare Colonization in Peritoneum After Blunt Abdominal Trauma: S. putrefaciens
      and S. cerevisiae
AB  - BACKGROUND: Shewanella spp. are gram-negative bacteria, saprophytes, and rarely
      pathogenic. Saccharomyces cerevisiae is the well-known yeast used for
      fermentation in industry and molecular biology for research. In humans, it is a
      very rare pathogen which colonizes the digestive tract, and its utility has been
      linked to the treatment and prevention of diarrhea associated with Clostridium
      difficile. CASE REPORT: A 27-year-old male, victim of aggressive, blunt trauma
      with a 4-day history of symptoms was admitted to our surgery unit. Abdominal
      sonography revealed peritoneal fluid in all spaces with fibrin. We performed
      laparotomy and observed perforations on the ileum and general peritonitis with
      pus. Following surgery, patient was admitted to the intensive care unit with
      septic shock. The antibiogram from the peritoneal liquid revealed S. putrefaciens
      and S. cerevisiae. CONCLUSION: Although very rare, S. putrefaciens and S.
      cerevisiae may colonize in the peritoneum after blunt abdominal trauma.

PMID- 29449199
TI  - Implementation of Digital Awareness Strategies to Engage Patients and Providers
      in a Lung Cancer Screening Program: Retrospective Study.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related deaths in the
      United States. Despite mandated insurance coverage for eligible patients, lung
      cancer screening rates remain low. Digital platforms, including social media,
      provide a potentially valuable tool to enhance health promotion and patient
      engagement related to lung cancer screening (LCS). OBJECTIVE: The aim was to
      assess the effectiveness of LCS digital awareness campaigns on utilization of low
      dose computed tomography (LDCT) and visits to institutional online educational
      content. METHODS: A pay-per-click campaign utilizing Google and Facebook targeted
      adults aged 55 years and older and caregivers aged 18 years and older (eg,
      spouses, adult children) with LCS content during a 20-week intervention period
      from May to September 2016. A concurrent pay-per-click campaign using LinkedIn
      and Twitter targeted health care providers with LCS content. Geographic target
      radius was within 60 miles of an academic medical center. Social media data
      included aggregate demographics and click-through rates (CTRs). Primary outcome
      measures were visits to institutional Web pages and scheduled LDCT exams. Study
      period was 20 weeks before, during, and after the digital awareness campaigns.
      RESULTS: Weekly visits to the institutional LCS Web pages were significantly
      higher during the digital awareness campaigns compared to the 20-week period
      prior to implementation (mean 823.9, SD 905.8 vs mean 51, SD 22.3, P=.001). The
      patient digital awareness campaign surpassed industry standard CTRs on Google
      (5.85%, 1108/18,955 vs 1.8%) and Facebook (2.59%, 47,750/1,846,070 vs 0.8%). The
      provider digital awareness campaign surpassed industry standard CTR on LinkedIn
      (1.1%, 630/57,079 vs 0.3%) but not Twitter (0.19%, 1139/587,133 vs 0.25%). Mean
      scheduled LDCT exam volumes per week before, during, and after the digital
      awareness campaigns were 17.4 (SD 7.5), 20.4 (SD 5.4), and 26.2 (SD 6.4),
      respectively, with the difference between the mean number of scheduled exams
      after the digital awareness campaigns and the number of exams scheduled before
      and after the digital awareness campaigns being statistically significant
      (P<.001). CONCLUSIONS: Implementation of the LCS digital awareness campaigns was
      associated with increased visits to institutional educational Web pages and
      scheduled LDCT exams. Digital platforms are an important tool to enhance health
      promotion activities and engagement with patients and providers.

PMID- 29449200
TI  - mHealth Technology and Nurse Health Coaching to Improve Health in Diabetes:
      Protocol for a Randomized Controlled Trial.
AB  - BACKGROUND: Chronic diseases, including diabetes mellitus, are the leading cause
      of mortality and disability in the United States. Current solutions focus
      primarily on diagnosis and pharmacological treatment, yet there is increasing
      evidence that patient-centered models of care are more successful in improving
      and addressing chronic disease outcomes. OBJECTIVE: The objective of this
      clinical trial is to evaluate the impact of a mobile health (mHealth) enabled
      nurse health coaching intervention on self-efficacy among adults with type-2
      diabetes mellitus. METHODS: A randomized controlled trial was conducted at an
      academic health system in Northern California. A total of 300 participants with
      type-2 diabetes were scheduled to be enrolled through three primary care clinics.
      Participants were randomized to either usual care or intervention. All
      participants received training on use of the health system patient portal.
      Participants in the intervention arm received six scheduled health-coaching
      telephone calls with a registered nurse and were provided with an activity
      tracker and mobile application that integrated data into the electronic health
      record (EHR) to track their daily activity and health behavior decisions. All
      participants completed a baseline survey and follow-up surveys at 3 and 9 months.
      Primary and secondary outcomes include diabetes self-efficacy, hemoglobin A1c
      (HbA1c), and quality of life measures. RESULTS: Data collection for this trial,
      funded by the Patient-Centered Outcomes Research Institute, will be completed by
      December 2017. Results from the trial will be available mid-2018. CONCLUSIONS:
      This protocol details a patient-centered intervention using nurse health
      coaching, mHealth technologies, and integration of patient-generated data into
      the EHR. The aim of the intervention is to enhance self-efficacy and health
      outcomes by providing participants with a mechanism to track daily activity by
      offering coaching support to set reasonable and attainable health goals, and by
      creating a complete feedback loop by bringing patient-generated data into the
      EHR. TRIAL REGISTRATION: ClinicalTrials.gov NCT02672176;
      https://clinicaltrials.gov/ct2/show/NCT02672176 (Archived by WebCite at
      http://www.webcitation.org/6xEQXe1M5).

PMID- 29449201
TI  - Peer Coaching Through mHealth Targeting Physical Activity in People With
      Parkinson Disease: Feasibility Study.
AB  - BACKGROUND: Long-term engagement in exercise and physical activity mitigates the
      progression of disability and increases quality of life in people with Parkinson
      disease (PD). Despite this, the vast majority of individuals with PD are
      sedentary. There is a critical need for a feasible, safe, acceptable, and
      effective method to assist those with PD to engage in active lifestyles. Peer
      coaching through mobile health (mHealth) may be a viable approach. OBJECTIVE: The
      purpose of this study was to develop a PD-specific peer coach training program
      and a remote peer-mentored walking program using mHealth technology with the goal
      of increasing physical activity in persons with PD. We set out to examine the
      feasibility, safety, and acceptability of the programs along with preliminary
      evidence of individual-level changes in walking activity, self-efficacy, and
      disability in the peer mentees. METHODS: A peer coach training program and a
      remote peer-mentored walking program using mHealth was developed and tested in 10
      individuals with PD. We matched physically active persons with PD (peer coaches)
      with sedentary persons with PD (peer mentees), resulting in 5 dyads. Using both
      Web-based and in-person delivery methods, we trained the peer coaches in basic
      knowledge of PD, exercise, active listening, and motivational interviewing. Peer
      coaches and mentees wore FitBit Zip activity trackers and participated in daily
      walking over 8 weeks. Peer dyads interacted daily via the FitBit friends mobile
      app and weekly via telephone calls. Feasibility was determined by examining
      recruitment, participation, and retention rates. Safety was assessed by
      monitoring adverse events during the study period. Acceptability was assessed via
      satisfaction surveys. Individual-level changes in physical activity were examined
      relative to clinically important differences. RESULTS: Four out of the 5 peer
      pairs used the FitBit activity tracker and friends function without difficulty. A
      total of 4 of the 5 pairs completed the 8 weekly phone conversations. There were
      no adverse events over the course of the study. All peer coaches were "satisfied"
      or "very satisfied" with the training program, and all participants were
      "satisfied" or "very satisfied" with the peer-mentored walking program. All
      participants would recommend this program to others with PD. Increases in average
      steps per day exceeding the clinically important difference occurred in 4 out of
      the 5 mentees. CONCLUSIONS: Remote peer coaching using mHealth is feasible, safe,
      and acceptable for persons with PD. Peer coaching using mHealth technology may be
      a viable method to increase physical activity in individuals with PD. Larger
      controlled trials are necessary to examine the effectiveness of this approach.

PMID- 29449202
TI  - A Web-Based Psychoeducational Intervention for Adolescent Depression: Design and
      Development of MoodHwb.
AB  - BACKGROUND: Depression is common in adolescence and leads to distress and
      impairment in individuals, families and carers. Treatment and prevention
      guidelines highlight the key role of information and evidence-based psychosocial
      interventions not only for individuals but also for their families and carers.
      Engaging young people in prevention and early intervention programs is a
      challenge, and early treatment and prevention of adolescent depression is a major
      public health concern. There has been growing interest in psychoeducational
      interventions to provide accurate information about health issues and to enhance
      and develop self-management skills. However, for adolescents with, or at high
      risk of depression, there is a lack of engaging Web-based psychoeducation
      programs that have been developed with user input and in line with research
      guidelines and targeted at both the individual and their family or carer. There
      are also few studies published on the process of development of Web-based
      psychoeducational interventions. OBJECTIVE: The aim of this study was to describe
      the process underlying the design and development of MoodHwb (HwbHwyliau in
      Welsh): a Web-based psychoeducation multimedia program for young people with, or
      at high risk of, depression and their families, carers, friends, and
      professionals. METHODS: The initial prototype was informed by (1) a systematic
      review of psychoeducational interventions for adolescent depression; (2) findings
      from semistructured interviews and focus groups conducted with adolescents (with
      depressive symptoms or at high risk), parents or carers, and professionals
      working with young people; and (3) workshops and discussions with a multimedia
      company and experts (in clinical, research, and multimedia work). Twelve
      interviews were completed (four each with young people, parents or carers, and
      professionals) and six focus groups (three with young people, one with parents
      and carers, one with professionals, and one with academics). RESULTS: Key themes
      from the interviews and focus groups were: aims of the program, design and
      content issues, and integration and context of the program. The prototype was
      designed to be person-centered, multiplatform, engaging, interactive, and
      bilingual. It included mood-monitoring and goal-setting components and was
      available as a Web-based program and an app for mobile technologies. CONCLUSIONS:
      MoodHwb is a Web-based psychoeducational intervention developed for young people
      with, or at high risk of, depression and their families and carers. It was
      developed with user input using qualitative methods as well as user-centered
      design and educational and psychological theory. Further research is needed to
      evaluate the effectiveness of the program in a randomized controlled trial. If
      found to be effective, it could be implemented in health, education, youth and
      social services, and charities, to not only help young people but also families,
      carers, friends, and professionals involved in their care.

PMID- 29449203
TI  - Influencing the Conversation About Masculinity and Suicide: Evaluation of the Man
      Up Multimedia Campaign Using Twitter Data.
AB  - BACKGROUND: It has been suggested that some dominant aspects of traditional
      masculinity are contributing to the high suicide rates among Australian men. We
      developed a three-episode documentary called Man Up, which explores the complex
      relationship between masculinity and suicide and encourages men to question
      socially imposed rules about what it means to be a man and asks them to open up,
      express difficult emotions, and seek help if and when needed. We ran a three
      phase social media campaign alongside the documentary using 5 channels (Twitter,
      Facebook, Instagram, YouTube, and Tumblr). OBJECTIVE: This study aimed to examine
      the extent to which the Man Up Twitter campaign influenced the social media
      conversation about masculinity and suicide. METHODS: We used Twitter insights
      data to assess the reach of and engagement with the campaign (using metrics on
      followers, likes, retweets, and impressions) and to determine the highest and
      lowest performing tweets in the campaign (using an aggregated performance measure
      of reactions). We used original content tweets to determine whether the campaign
      increased the volume of relevant Twitter conversations (aggregating the number of
      tweets for selected campaign hashtags over time), and we used a subset of these
      data to gain insight into the main content themes with respect to audience
      engagement. RESULTS: The campaign generated a strong following that was engaged
      with the content of the campaign; over its whole duration, the campaign earned
      approximately 5000 likes and 2500 retweets and gained around 1,022,000
      impressions. The highest performing tweets posted by the host included video
      footage and occurred during the most active period of the campaign (around the
      screening of the documentary). The volume of conversations in relation to
      commonly used hashtags (#MANUP, #ABCMANUP, #LISTENUP, and #SPEAKUP) grew in
      direct relation to the campaign activities, achieving strongest growth during the
      3 weeks when the documentary was aired. Strongest engagement was found with
      content related to help-seeking, masculinity, and expressing emotions. A number
      of followers tweeted personal stories that revealed overwhelmingly positive
      perceptions of the content of the documentary and strongly endorsed its messages.
      CONCLUSIONS: The Man Up Twitter campaign triggered conversations about
      masculinity and suicide that otherwise may not have happened. For some, this may
      have been game-changing in terms of shifting attitudes toward expressing emotions
      and reaching out to others for help. The campaign was particularly effective in
      disseminating information and promoting conversations in real time, an advantage
      that it had over more traditional health promotion campaigns. This sort of
      approach could well be adapted to other areas of mental (and physical) health
      promotion campaigns to increase their reach and effectiveness.

PMID- 29449205
TI  - Infographic. Impact of the Nordic hamstring and hip extension exercises on
      hamstring architecture and morphology: implications for injury prevention.

PMID- 29449204
TI  - National Food, Nutrition, and Physical Activity Survey of the Portuguese General
      Population (2015-2016): Protocol for Design and Development.
AB  - BACKGROUND: The assessment of food consumption data using harmonized
      methodologies at the European level is fundamental to support the development of
      public policies. Portugal is one of the countries with the most outdated
      information on individual food consumption. OBJECTIVE: The objective of this
      study was to describe the design and methodology of the National Food, Nutrition
      and Physical Activity Survey, 2015-2016, developed to collect national and
      regional data on dietary habits, physical activity (PA), and nutritional status,
      in a representative sample of the Portuguese general population (3 months-84
      years). METHODS: Participants were selected by multistage sampling, using the
      National Heath Registry as the sampling frame. Data collection, during 12 months,
      was harmonized according to European guidelines (EU-MENU, European Food Safety
      Authority [EFSA]). Computer-assisted personal interviewing (CAPI) was performed
      on a specific electronic platform synchronized with nutritional composition data
      and considering the FoodEx2 classification system. Dietary assessment was
      performed using 24-hour recalls (two nonconsecutive, 8-15 days apart) or food
      diaries in the case of children aged <10 years, complemented with a food
      propensity questionnaire; PA data (International Physical Activity Questionnaire
      [IPAQ], the Activity Choice Index [ACI], and 4-days PA diaries); sociodemographic
      data, and other health-related data were also collected. RESULTS: A sample of
      6553 individuals completed the first interview, and 5811 participants completed
      two dietary assessments. The participation rate among eligible individuals was
      33.38% (6553/19,635), considering the first interview, and 29.60% (5811/19,635)
      for the participants with two completed interviews (about 40% in children and
      adolescents and 20% in elderly individuals). Results of the survey will be
      disseminated in national and international scientific journals during 2018-2019.
      CONCLUSIONS: The survey will assist policy planning and management of national
      and European health programs on the improvement of nutritional status and risk
      assessment related to food hazards, and the enhancement of PA. The
      infrastructures and data driven from this Survey are a solid basis to the
      development of a future national surveillance system on diet, PA, and other
      health behaviors reproducible over time.

PMID- 29449206
TI  - Infographic. Is lower hip range of motion a risk factor for groin pain in
      athletes? A systematic review with clinical applications.

PMID- 29449207
TI  - Different interventions, same outcomes? Here are four good reasons.

PMID- 29449209
TI  - Don't distract from true issues facing young doctors, BMA tells pay body.

PMID- 29449208
TI  - Everyone with asthma should have a metered dose inhaler and a spacer.

PMID- 29449210
TI  - E-cigarette liquid ingestion: a fast growing accidental issue in children.

PMID- 29449211
TI  - Long-term prognosis after childhood kidney disease.

PMID- 29449212
TI  - Cannabis as an anticonvulsant.

PMID- 29449213
TI  - Inflammatory morphea presenting as a hemifacial acquired port-wine stain.

PMID- 29449214
TI  - Invasive bacterial infections in young afebrile infants with a history of fever.
AB  - OBJECTIVE: To determine the prevalence of invasive bacterial infections (IBI,
      pathogenic bacteria in blood or cerebrospinal fluid) in infants less than 90 days
      old with fever without a source related to the presence or absence of fever on
      arrival to the emergency department (ED). DESIGN: Prospective registry-based
      cohort study. SETTING: Paediatric ED of a tertiary teaching hospital. PATIENTS:
      We included infants less than 90 days old with a history of fever evaluated in
      the ED from 2003 to 2016. MAIN OUTCOMES AND MEASURES: The prevalence of IBI in
      patients with a history of fever who were febrile and afebrile on arrival to the
      ED. RESULTS: We included 2470 infants: 678 afebrile and 1792 febrile when
      evaluated in the ED. Fifty-nine (2.4%) were diagnosed with an IBI (bacteraemia
      46, meningitis 7 and sepsis 6): 16 in the group of afebrile infants with a
      history of fever (2.4%, 95% CI 1.4 to 3.8 vs 43 in the febrile group, 2.4%, 95%
      CI 1.8 to 3.2). Of the 16 afebrile infants with a history of fever diagnosed with
      an IBI, 14 were well appearing. The rate of non-IBI (pathogenic bacteria in urine
      or stools) was similar in both groups (15.5% and 16.7%). CONCLUSIONS: The
      prevalence of IBI in infants <=90 days with a history of fever is similar
      regardless of the presence of fever on the arrival at the ED. The approach to
      infants with a history of fever who are afebrile in the ED should not differ from
      that recommended for infants who are febrile in the ED.

PMID- 29449215
TI  - Trisomy 18: palliative surgical intervention.

PMID- 29449216
TI  - Adjustable delivery of pro-angiogenic FGF-2 by alginate:collagen microspheres.
AB  - Therapeutic induction of blood vessel growth (angiogenesis) in ischemic tissues
      holds great potential for treatment of myocardial infarction and stroke.
      Achieving sustained angiogenesis and vascular maturation has, however, been
      highly challenging. Here, we demonstrate that alginate:collagen hydrogels
      containing therapeutic, pro-angiogenic FGF-2, and formulated as microspheres, is
      a promising and clinically relevant vehicle for therapeutic angiogenesis. By
      titrating the amount of readily dissolvable and degradable collagen with more
      slowly degradable alginate in the hydrogel mixture, the degradation rates of the
      biomaterial controlling the release kinetics of embedded pro-angiogenic FGF-2 can
      be adjusted. Furthermore, we elaborate a microsphere synthesis protocol allowing
      accurate control over sphere size, also a critical determinant of
      degradation/release rate. As expected, alginate:collagen microspheres were
      completely biocompatible and did not cause any adverse reactions when injected in
      mice. Importantly, the amount of pro-angiogenic FGF-2 released from such
      microspheres led to robust induction of angiogenesis in zebrafish embryos similar
      to that achieved by injecting FGF-2-releasing cells. These findings highlight the
      use of microspheres constructed from alginate:collagen hydrogels as a promising
      and clinically relevant delivery system for pro-angiogenic therapy.

PMID- 29449217
TI  - ZFP36L2 is a cell cycle-regulated CCCH protein necessary for DNA lesion-induced S
      phase arrest.
AB  - ZFP36L2 promotes the destruction of AU-rich element-containing transcripts, while
      its regulation and functional significance in cell cycle control are scarcely
      identified. We show that ZFP36L2 is a cell cycle-regulated CCCH protein, the
      abundance of which is regulated post-translationally at the respective stages of
      the cell cycle. Indeed, ZFP36L2 protein was eliminated after release from M
      phase, and ZYG11B-based E3 ligase plays a role in its polyubiquitination in
      interphase. Although ZFP36L2 is dispensable for normal cell cycle progression, we
      found that endogenous ZFP36L2 played a key role in cisplatin-induced S-phase
      arrest, a process in which the suppression of G1/S cyclins is necessary. The
      accumulation of ZFP36L2 was stimulated under DNA replication stresses and altered
      interactions with a subset of RNA-binding proteins. Notably, silencing endogenous
      ZFP36L2 led to impaired cell viability in the presence of cisplatin-induced DNA
      lesions. Thus, we propose that ZFP36L2 is a key protein that controls S-phase
      progression in the case of genome instability.

PMID- 29449218
TI  - Arthroscopic surgery for degenerative knee arthritis and meniscal tears: a
      clinical practice guideline.

PMID- 29449221
TI  - "Muddy waters" surround evidence for opt-out system of organ donation, says
      surgeon.

PMID- 29449220
TI  - NICE recommends kidney cancer drug "likely to be less effective" than current
      treatments after price deal.

PMID- 29449219
TI  - Interventions to reduce sedentary behaviour in 0-5-year-olds: a systematic review
      and meta-analysis of randomised controlled trials.
AB  - AIM OR OBJECTIVE: To evaluate the effectiveness of behavioural interventions that
      report sedentary behaviour outcomes during early childhood. DESIGN: Systematic
      review and meta-analysis. DATA SOURCES: Academic Search Complete, CINAHL
      Complete, Global Health, MEDLINE Complete, PsycINFO, SPORTDiscus with Full Text
      and EMBASE electronic databases were searched in March 2016. ELIGIBILITY CRITERIA
      FOR SELECTING STUDIES: Inclusion criteria were: (1) published in a peer-reviewed
      English language journal; (2) sedentary behaviour outcomes reported; (3)
      randomised controlled trial (RCT) study design; and (4) participants were
      children with a mean age of <=5.9 years and not yet attending primary/elementary
      school at postintervention. RESULTS: 31 studies were included in the systematic
      review and 17 studies in the meta-analysis. The overall mean difference in screen
      time outcomes between groups was -17.12 (95% CI -28.82 to -5.42) min/day with a
      significant overall intervention effect (Z=2.87, p=0.004). The overall mean
      difference in sedentary time between groups was -18.91 (95% CI -33.31 to -4.51)
      min/day with a significant overall intervention effect (Z=2.57, p=0.01). Subgroup
      analyses suggest that for screen time, interventions of >=6 months duration and
      those conducted in a community-based setting are most effective. For sedentary
      time, interventions targeting physical activity (and reporting changes in
      sedentary time) are more effective than those directly targeting sedentary time.
      SUMMARY/CONCLUSIONS: Despite heterogeneity in study methods and results, overall
      interventions to reduce sedentary behaviour in early childhood show significant
      reductions, suggesting that this may be an opportune time to intervene. TRIAL
      REGISTRATION NUMBER: CRD42015017090.

PMID- 29449222
TI  - How many lives are at stake? Assessing 2030 sustainable development goal
      trajectories for maternal and child health.

PMID- 29449223
TI  - GMC pushes for automatic erasure when a doctor is convicted of a serious crime.

PMID- 29449225
TI  - The cannabis paradox.

PMID- 29449224
TI  - Natural killer receptor ligand expression on acute myeloid leukemia impacts
      survival and relapse after chemotherapy.
AB  - Natural killer (NKs) cells provide rapid responses to viral-infected and
      malignant cells, including acute myeloid leukemia (AML) blasts. The balance among
      inhibitory and activating signals, delivered by multiple interactions between
      ligands on target cells and NK receptors, determines the posture of the NK cell
      response to either one of target cell elimination or tolerance. The aim of this
      work was to study the influence of the differential expression of activating and
      inhibitory NK receptor ligands (NKRLs) by leukemic blasts on clinical outcome in
      newly diagnosed AML patients. Leukemic cells and clinical data from 66 patients
      undergoing induction chemotherapy were obtained from the Australasian Leukemia
      Lymphoma Group tissue bank. Expression of 6 activating (MICA, MICAB, CD155,
      CD112, ULBP1, and ULBP2/5/6) and 3 inhibitory (HLA class I, PD-L1, and PD-L2)
      NKRLs was analyzed by flow cytometry. AML blasts displayed heterogeneous
      expression of NKRLs. MICA, CD112, and ULBP1 were most frequently expressed. ULBP1
      expression was significantly associated with improved 2-year overall survival
      (51.4% vs 11.4%), relapse-free survival (42.5% vs 10.0%), and reduced relapse
      (44.1% vs 78.6%). We calculated a net score of activating minus inhibitory
      ligands and demonstrated that the expression of an overall activating NK ligand
      phenotype was associated with superior 2-year overall survival (59.6% vs 24.4%)
      and reduced relapse (31.5% vs 68.2%). Our study provides clinical evidence for
      the role of NK cell-mediated immunoediting against AML, mediated by the
      expression of NKRLs on blasts, and supports investigation into strategies to
      enhance NK cell function to improve outcomes in patients with AML.

PMID- 29449226
TI  - ?

PMID- 29449227
TI  - Prevalence of intestinal parasitic infections among asylum seekers.

PMID- 29449228
TI  - ?

PMID- 29449229
TI  - Acknowledging stigma.

PMID- 29449230
TI  - Correction.

PMID- 29449231
TI  - HeadsUpGuys: Canadian online resource for men with depression.

PMID- 29449232
TI  - New category of opioid-related death.

PMID- 29449233
TI  - Dangerous ideas: Top 3 proposals presented at Family Medicine Forum.

PMID- 29449234
TI  - Fantastic idea: Admit patients to hospital administratively so they can access
      medications.

PMID- 29449235
TI  - Amazing idea: Blind medical school and CaRMS applications of all applicant names
      until interview selections are complete.

PMID- 29449236
TI  - ?

PMID- 29449237
TI  - Will the new opioid guidelines harm more people than they help? Yes.

PMID- 29449238
TI  - Will the new opioid guidelines harm more people than they help? No.

PMID- 29449239
TI  - ?

PMID- 29449240
TI  - ?

PMID- 29449242
TI  - Novel case of maternal and neonatal kratom dependence and withdrawal.

PMID- 29449241
TI  - Simplified guideline for prescribing medical cannabinoids in primary care.
AB  - OBJECTIVE: To develop a clinical practice guideline for a simplified approach to
      medical cannabinoid use in primary care; the focus was on primary care
      application, with a strong emphasis on best available evidence and a promotion of
      shared, informed decision making. METHODS: The Evidence Review Group performed a
      detailed systematic review of 4 clinical areas with the best evidence around
      cannabinoids: pain, nausea and vomiting, spasticity, and adverse events. Nine
      health professionals (2 generalist family physicians, 2 pain management-focused
      family physicians, 1 inner-city family physician, 1 neurologist, 1 oncologist, 1
      nurse practitioner, and 1 pharmacist) and a patient representative comprised the
      Prescribing Guideline Committee (PGC), along with 2 nonvoting members (pharmacist
      project managers). Member selection was based on profession, practice setting,
      location, and lack of financial conflicts of interest. The guideline process was
      iterative through content distribution, evidence review, and telephone and online
      meetings. The PGC directed the Evidence Review Group to address and provide
      evidence for additional questions as needed. The key recommendations were derived
      through consensus of the PGC. The guideline was drafted, refined, and distributed
      to a group of clinicians and patients for feedback, then refined again and
      finalized by the PGC. RECOMMENDATIONS: Recommendations include limiting medical
      cannabinoid use in general, but also outline potential restricted use in a small
      subset of medical conditions for which there is some evidence (neuropathic pain,
      palliative and end-of-life pain, chemotherapy-induced nausea and vomiting, and
      spasticity due to multiple sclerosis or spinal cord injury). Other important
      considerations regarding prescribing are reviewed in detail, and content is
      offered to support shared, informed decision making. CONCLUSION: This simplified
      medical cannabinoid prescribing guideline provides practical recommendations for
      the use of medical cannabinoids in primary care. All recommendations are intended
      to assist with, not dictate, decision making in conjunction with patients.

PMID- 29449243
TI  - Schistosomiasis in a returning international traveler with cyclic fevers and
      diarrhea.

PMID- 29449244
TI  - Fine-needle aspiration biopsy of thyroid nodules: Determining when it is
      necessary.

PMID- 29449246
TI  - We do what we can.

PMID- 29449245
TI  - Selection for family medicine residency training in Canada: How consistently are
      the same students ranked by different programs?
AB  - OBJECTIVE: To examine the consistency of the ranking of Canadian and US medical
      graduates who applied to Canadian family medicine (FM) residency programs between
      2007 and 2013. DESIGN: Descriptive cross-sectional study. SETTING: Family
      medicine residency programs in Canada. PARTICIPANTS: All 17 Canadian medical
      schools allowed access to their anonymized program rank-order lists of students
      applying to FM residency programs submitted to the first iteration of the
      Canadian Resident Matching Service match from 2007 to 2013. MAIN OUTCOME
      MEASURES: The rank position of medical students who applied to more than 1 FM
      residency program on the rank-order lists submitted by the programs. Anonymized
      ranking data submitted to the Canadian Resident Matching Service from 2007 to
      2013 by all 17 FM residency programs were used. Ranking data of eligible Canadian
      and US medical graduates were analyzed to assess the within-student and between
      student variability in rank score. These covariance parameters were then used to
      calculate the intraclass correlation coefficient (ICC) for all programs. Program
      descriptions and selection criteria were also reviewed to identify sites with
      similar profiles for subset ICC analysis. RESULTS: Between 2007 and 2013, the
      consistency of ranking by all programs was fair at best (ICC = 0.34 to 0.39). The
      consistency of ranking by larger urban-based sites was weak to fair (ICC = 0.23
      to 0.36), and the consistency of ranking by sites focusing on training for rural
      practice was weak to moderate (ICC = 0.16 to 0.55). CONCLUSION: In most cases,
      there is a low level of consistency of ranking of students applying for FM
      training in Canada. This raises concerns regarding fairness, particularly in
      relation to expectations around equity and distributive justice in selection
      processes.

PMID- 29449247
TI  - Wanting family medicine without primary care.

PMID- 29449248
TI  - Family Medicine Professional Profile.

PMID- 29449249
TI  - ?

PMID- 29449250
TI  - ?

PMID- 29449251
TI  - Enhanced skills in family medicine: update.

PMID- 29449252
TI  - ?

PMID- 29449253
TI  - ?

PMID- 29449254
TI  - ?

PMID- 29449255
TI  - ?

PMID- 29449256
TI  - Rebuttal: Will the new opioid guidelines harm more people than they help? Yes.

PMID- 29449257
TI  - ?

PMID- 29449258
TI  - ?

PMID- 29449259
TI  - ?

PMID- 29449261
TI  - ?

PMID- 29449260
TI  - ?

PMID- 29449264
TI  - ?

PMID- 29449263
TI  - Patterns of methadone maintenance treatment provision in Ontario: Policy success
      or pendulum excess?
AB  - OBJECTIVE: To describe recent trends and patterns in methadone maintenance
      treatment (MMT) practice regionally and over time in the province of Ontario.
      DESIGN: Population-based descriptive study using health administrative data
      between September 1, 2011, and December 31, 2014. SETTING: Ontario. PARTICIPANTS:
      All active MMT-prescribing physicians and patients receiving MMT in the study
      period. MAIN OUTCOME MEASURES: Characteristics of MMT-prescribing physicians,
      including age, sex, specialty type, practice region, and practice volume;
      characteristics of patients receiving MMT, including age, sex, neighbourhood
      income, and region of residence. RESULTS: Between September 1, 2011, and December
      31, 2014, the number of MMT-prescribing physicians and patients who received MMT
      increased by 26% and 42%, respectively. In 2014, there was a total of 312 MMT
      prescribing physicians and 49 703 patients receiving MMT. In 2014 and on a per
      capita basis, patients receiving MMT were more prevalent in rural regions; and
      within rural regions, there were disproportionately large numbers of young female
      MMT patients residing in low-income neighbourhoods. CONCLUSION: The number of
      physicians prescribing MMT and patients receiving MMT has increased substantially
      between 2011 and 2014, with the largest per capita distribution occurring in
      rural regions and involving young adults. While availability of and access to MMT
      has improved considerably from before 2000 to levels of high use, these
      developments are likely influenced by recent trends in the proliferation of
      prescription opioid misuse across general populations.

PMID- 29449262
TI  - Systematic review of systematic reviews for medical cannabinoids: Pain, nausea
      and vomiting, spasticity, and harms.
AB  - OBJECTIVE: To determine the effects of medical cannabinoids on pain, spasticity,
      and nausea and vomiting, and to identify adverse events. DATA SOURCES: MEDLINE,
      the Cochrane Database, and the references of included studies were searched.
      STUDY SELECTION: Systematic reviews with 2 or more randomized controlled trials
      (RCTs) that focused on medical cannabinoids for pain, spasticity, or nausea and
      vomiting were included. For adverse events, any meta-analysis for the conditions
      listed or of adverse events of cannabinoids was included. SYNTHESIS: From 1085
      articles, 31 relevant systematic reviews were identified including 23 for pain, 5
      for spasticity, 6 for nausea and vomiting, and 12 for adverse events. Meta
      analysis of 15 RCTs found more patients taking cannabinoids attained at least a
      30% pain reduction: risk ratio (RR) of 1.37 (95% CI 1.14 to 1.64), number needed
      to treat (NNT) of 11. Sensitivity analysis found study size and duration affected
      findings (subgroup differences, P <= .03), with larger and longer RCTs finding no
      benefit. Meta-analysis of 4 RCTs found a positive global impression of change in
      spasticity (RR = 1.45, 95% CI 1.08 to 1.95, NNT = 7). Other results were not
      consistently statistically significant, but when positive, a 30% or more
      improvement in spasticity had an NNT of 10. Meta-analysis of 7 RCTs for control
      of nausea and vomiting after chemotherapy found an RR of 3.60 (95% CI 2.55 to
      5.09) with an NNT of 3. Adverse effects caused more patients to stop treatment
      (number needed to harm [NNH] of 8 to 22). Individual adverse events were very
      common, including dizziness (NNH = 5), sedation (NNH = 5), confusion (NNH = 15),
      and dissociation (NNH = 20). "Feeling high" was reported in 35% to 70% of users.
      The GRADE (Grading of Recommendations Assessment, Development and Evaluation)
      evaluation reduced evidence ratings of benefit to low or very low. CONCLUSION:
      There is reasonable evidence that cannabinoids improve nausea and vomiting after
      chemotherapy. They might improve spasticity (primarily in multiple sclerosis).
      There is some uncertainty about whether cannabinoids improve pain, but if they
      do, it is neuropathic pain and the benefit is likely small. Adverse effects are
      very common, meaning benefits would need to be considerable to warrant trials of
      therapy.

PMID- 29449265
TI  - Patients find it easy to select data they don't want to share.

PMID- 29449266
TI  - Fungal liver abscess in an immunocompetent patient who underwent repeated ERCPs
      and subtotal cholecystectomy.
AB  - We report a case of a previously healthy female patient who initially presented
      with fever, jaundice and right upper quadrant pain three days after dilatation
      and stenting of a stricture of the common bile duct (CBD). During an earlier
      admission, the patient had undergone endoscopic retrograde
      cholangiopancreatography (ERCP) having presented with fevers and biliary
      dilatation on ultrasound. The ERCP features were more consistent with Mirizzi's
      Syndrome. The patient subsequently underwent subtotal cholecystectomy and later
      developed a CBD stricture, requiring repeat ERCP and stent insertion. At
      presentation, she had moderately deranged liver function tests and significantly
      elevated inflammatory markers and was found on cross-sectional imaging to have
      developed a liver abscess. Aspiration of the lesion cultured Candida albicans She
      was treated with intravenous antifungals, broad-spectrum antibiotics and further
      aspiration of abscess, which contributed towards her successful recovery. Fungal
      liver abscess should be suspected in immunocompetent patients who undergo ERCP
      and or cholecystectomy.

PMID- 29449268
TI  - Seven days in medicine: 7-13 February 2018.

PMID- 29449267
TI  - Single-Cell Transcriptome Analyses Reveal Endothelial Cell Heterogeneity in
      Tumors and Changes following Antiangiogenic Treatment.
AB  - Angiogenesis involves dynamic interactions between specialized endothelial tip
      and stalk cells that are believed to be regulated in part by VEGF and Dll4-Notch
      signaling. However, our understanding of this process is hampered by limited
      knowledge of the heterogeneity of endothelial cells and the role of different
      signaling pathways in specifying endothelial phenotypes. Here, we characterized
      by single-cell transcriptomics the heterogeneity of mouse endothelial cells and
      other stromal cells during active angiogenesis in xenograft tumors as well as
      from adult normal heart, following pharmacologic inhibition of VEGF and Dll4
      Notch signaling. We classified tumor endothelial cells into three subpopulations
      that appeared to correspond with tip-like, transition, and stalk-like cells.
      Previously identified markers for tip and stalk cells were confirmed and several
      novel ones discovered. Blockade of VEGF rapidly inhibited cell-cycle genes and
      strongly reduced the proportion of endothelial tip cells in tumors. In contrast,
      blockade of Dll4 promoted endothelial proliferation as well as tip cell markers;
      blockade of both pathways inhibited endothelial proliferation but preserved some
      tip cells. We also phenotypically classified other tumor stromal cells and found
      that tumor-associated fibroblasts responded to antiangiogenic drug treatments by
      upregulating hypoxia-associated genes and producing secreted factors involved in
      angiogenesis. Overall, our findings better define the heterogeneity of tumor
      endothelial and other stromal cells and reveal the roles of VEGF and Dll4-Notch
      in specifying tumor endothelial phenotype, highlighting the response of stromal
      cells to antiangiogenic therapies.Significance: These findings provide a
      framework for defining subpopulations of endothelial cells and tumor-associated
      fibroblasts and their rapid changes in gene expression following antiangiogenic
      treatment. Cancer Res; 78(9); 2370-82. (c)2018 AACR.

PMID- 29449269
TI  - Awhina Revolution: A Bayesian Analysis of Undergraduate and Postgraduate
      Completion Rates from a Program for Maori and Pacific Success in STEM
      Disciplines.
AB  - Maori and Pacific students generally do not attain the same levels of tertiary
      success as New Zealanders of European descent, particularly in science,
      technology, engineering, and mathematics (STEM) subjects. Te Ropu Awhina
      (Awhina), an equity initiative at Victoria University of Wellington in New
      Zealand between 1999 and 2015, aimed to produce Maori and Pacific professionals
      in STEM disciplines who contribute to Maori and Pacific community development and
      leadership. A hierarchical Bayesian approach was used to estimate posterior
      standardized completion rates for 3-year undergraduate and 2-year postgraduate
      degrees undertaken by non-Maori-Pacific and Maori-Pacific students. Results were
      consistent with an Awhina effect, that is, Awhina's positive influence on
      (combined) Maori and Pacific success.

PMID- 29449270
TI  - Internship Experiences Contribute to Confident Career Decision Making for
      Doctoral Students in the Life Sciences.
AB  - The Graduate Student Internships for Career Exploration (GSICE) program at the
      University of California, San Francisco (UCSF), offers structured training and
      hands-on experience through internships for a broad range of PhD-level careers.
      The GSICE program model was successfully replicated at the University of
      California, Davis (UC Davis). Here, we present outcome data for a total of 217
      PhD students participating in the UCSF and UC Davis programs from 2010 to 2015
      and 2014 to 2015, respectively. The internship programs at the two sites
      demonstrated comparable participation, internship completion rates, and overall
      outcomes. Using survey, focus group, and individual interview data, we find that
      the programs provide students with career development skills, while increasing
      students' confidence in career exploration and decision making. Internships, in
      particular, were perceived by students to increase their ability to discern a
      career area of choice and to increase confidence in pursuing that career. We
      present data showing that program participation does not change median time to
      degree and may help some trainees avoid "default postdocs." Our findings suggest
      important strategies for institutions developing internship programs for PhD
      students, namely: including a structured training component, allowing
      postgraduation internships, and providing a central organization point for
      internship programs.

PMID- 29449271
TI  - Targeted Therapies for Targeted Populations: Anti-EGFR Treatment for EGFR
      Amplified Gastroesophageal Adenocarcinoma.
AB  - Previous anti-EGFR trials in unselected patients with gastroesophageal
      adenocarcinoma (GEA) were resoundingly negative. We identified EGFR amplification
      in 5% (19/363) of patients at the University of Chicago, including 6% (8/140) who
      were prospectively screened with intention-to-treat using anti-EGFR therapy.
      Seven patients received >=1 dose of treatment: three first-line FOLFOX plus ABT
      806, one second-line FOLFIRI plus cetuximab, and three third/fourth-line
      cetuximab alone. Treatment achieved objective response in 58% (4/7) and disease
      control in 100% (7/7) with a median progression-free survival of 10 months.
      Pretreatment and posttreatment tumor next-generation sequencing (NGS), serial
      plasma circulating tumor DNA (ctDNA) NGS, and tumor IHC/FISH for EGFR revealed
      preexisting and/or acquired genomic events, including EGFR-negative clones, PTEN
      deletion, KRAS amplification/mutation, NRAS, MYC, and HER2 amplification, and
      GNAS mutations serving as mechanisms of resistance. Two evaluable patients
      demonstrated interval increase of CD3+ infiltrate, including one who demonstrated
      increased NKp46+, and PD-L1 IHC expression from baseline, suggesting an immune
      therapeutic mechanism of action. EGFR amplification predicted benefit from anti
      EGFR therapy, albeit until various resistance mechanisms emerged.Significance:
      This paper highlights the role of EGFR inhibitors in EGFR-amplified GEA-despite
      negative results in prior unselected phase III trials. Using serial ctDNA and
      tissue NGS, we identified mechanisms of primary and acquired resistance in all
      patients, as well as potential contribution of antibody-dependent cell-mediated
      cytotoxicity to their clinical benefit. Cancer Discov; 8(6); 696-713. (c)2018
      AACR.See related commentary by Strickler, p. 679This article is highlighted in
      the In This Issue feature, p. 663.

PMID- 29449272
TI  - Differential Clinical Outcomes Between Angiographic Complete Versus Incomplete
      Coronary Revascularization, According to the Presence of Chronic Kidney Disease
      in the Drug-Eluting Stent Era.
AB  - BACKGROUND: There are limited data regarding the prognostic impact of
      angiographic complete revascularization (CR) in patients with chronic kidney
      disease (CKD). We sought to investigate the differential prognostic impact of
      angiographic CR over incomplete revascularization (IR), according to the presence
      of CKD in the drug-eluting stent era. METHODS AND RESULTS: Between 2003 and 2011
      at Samsung Medical Center, consecutive patients with multivessel disease were
      stratified by the presence of CKD (estimated glomerular filtration rate <60
      mL/min per 1.73 m2) and classified according to angiographic CR (residual SYNTAX
      score=0) or IR. Clinical outcomes were compared between angiographic CR and IR,
      stratified by the presence of CKD. Primary outcome was patient-oriented composite
      outcomes (POCO, a composite of all-cause death, myocardial infarction, any
      revascularization) at 3 years. Inverse probability weighting was performed
      between the CR and IR groups. A total of 3224 patients were eligible for
      analysis: 2295 without CKD; 929 with CKD. Among non-CKD patients, angiographic CR
      showed a significantly lower risk of POCO than IR (17.2% versus 21.7%, adjusted
      hazard ratio 0.76, 95% confidence interval, 0.62-0.95, P=0.014), mainly driven by
      a significantly lower risk of any revascularization. Among CKD patients, however,
      angiographic CR was associated with a significantly higher risk of POCO than IR
      (37.7% versus 28.4%, adjusted hazard ratio 1.42, 95% confidence interval, 1.08%
      1.85%, P=0.011), mainly driven by a significantly higher risk of nonfatal target
      vessel myocardial infarction. CONCLUSIONS: Angiographic CR was associated with
      reduced risk of POCO than IR in patients without CKD; however, it was associated
      with a significantly higher risk of POCO and nonfatal myocardial infarction in
      CKD patients.

PMID- 29449273
TI  - Novel Patient-Centered Approach to Facilitate Same-Day Discharge in Patients
      Undergoing Elective Percutaneous Coronary Intervention.
AB  - BACKGROUND: Same-day discharge (SDD) after elective percutaneous coronary
      intervention is safe, less costly, and preferred by patients, but it is usually
      performed in low-risk patients, if at all. To increase the appropriate use of SDD
      in more complex patients, we implemented a "patient-centered" protocol based on
      risk of complications at Barnes-Jewish Hospital. METHODS AND RESULTS: Our
      objectives were as follows: (1) to evaluate time trends in SDD; (2) to compare
      (a) mortality, bleeding, and acute kidney injury, (b) patient satisfaction, and
      (c) hospital costs by SDD versus no SDD (NSDD); and (3) to compare SDD
      eligibility by our patient-centered approach versus Society for Cardiovascular
      Angiography and Interventions guidelines. Our patient-centered approach was based
      on prospectively identifying personalized bleeding, mortality, and acute kidney
      injury risks, with a personalized safe contrast limit and mitigating those risks.
      We analyzed Barnes-Jewish Hospital's National Cardiovascular Data Registry
      CathPCI Registry data from July 1, 2009 to September 30, 2015 (N=1752). SDD
      increased rapidly from 0% to 77% (P<0.001), independent of radial access.
      Although SDD patients were comparable to NSDD patients, SDD was not associated
      with adverse outcomes (0% mortality, 0% bleeds, and 0.4% acute kidney injury).
      Patient satisfaction was high with SDD. Propensity score-adjusted costs were
      $7331 lower/SDD patient (P<0.001), saving an estimated $1.8 million annually.
      Only 16 patients (6.95%) met the eligibility for SDD by Society for
      Cardiovascular Angiography and Interventions guidelines, implying our patient
      centered approach markedly increased SDD eligibility. CONCLUSIONS: With a patient
      centered approach, SDD rapidly increased and was safe in 75% of patients
      undergoing elective percutaneous coronary intervention, despite patient
      complexity. Patient satisfaction was high, and hospital costs were lower. Patient
      centered decision making to facilitate SDD is an important opportunity to improve
      the value of percutaneous coronary intervention.

PMID- 29449274
TI  - Clinical Relevance of Functionally Insignificant Moderate Coronary Artery
      Stenosis Assessed by 3-Vessel Fractional Flow Reserve Measurement.
AB  - BACKGROUND: Understanding of the risk conferred by functionally insignificant
      lesions in multiple coronary vessels is limited. We investigated the prognostic
      implications of coronary artery disease (CAD) based on 3-vessel fractional flow
      reserve (FFR). METHODS AND RESULTS: A total of 1,136 patients underwent FFR
      measurement in the 3 major epicardial arteries. We defined vessels with "Moderate
      CAD" as vessels with FFR, 0.81 to 0.87. Patients were classified into Group 1: No
      apparent CAD (FFR>0.87 in all 3-vessels); Group 2: Single-vessel moderate CAD;
      Group 3: Multivessel moderate CAD; and Group 4: Functionally significant CAD
      (FFR<=0.80) in any vessel. The primary end point was 2-year major adverse cardiac
      events, a composite of cardiac death, myocardial infarction, and ischemia-driven
      revascularization. Forty-three percent of patients had moderate CAD (Group 2:
      403/1136, 35.5%; Group 3: 84/1136, 7.4%). The 2-year risk of major adverse
      cardiac events was not significantly different between patients with single
      vessel moderate CAD and no apparent CAD (2.6 versus 2.6%; HR, 1.1; 95% confidence
      interval, 0.4%-2.8%; P=0.89). However, patients with multivessel moderate CAD
      were at significantly higher risk than Group 1 (7.4 versus 2.6%; hazard ratio,
      3.3; 95% confidence interval, 1.1%-9.8%; P=0.03). The risk of major adverse
      cardiac events in patients with multivessel moderate CAD was comparable to that
      of patients with functionally significant CAD (hazard ratio, 1.2; 95% confidence
      interval, 0.5%-3.0%; P=0.67). In a multivariable regression model, multivessel
      moderate CAD was an independent predictor of greater risk of 2-year major adverse
      cardiac events. CONCLUSIONS: Global physiologic assessment with FFR measurement
      of 3 vessels can identify multivessel moderate CAD. The prognostic implication of
      multivessel moderate CAD appears comparable to that of functionally significant
      CAD. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01621438.

PMID- 29449275
TI  - Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in
      classical Hodgkin lymphoma.
AB  - The rarity of neoplastic cells in the biopsy imposes major technical hurdles that
      have so far limited genomic studies in classical Hodgkin lymphoma (cHL). By using
      a highly sensitive and robust deep next-generation sequencing approach for
      circulating tumor DNA (ctDNA), we aimed to identify the genetics of cHL in
      different clinical phases, as well as its modifications on treatment. The
      analysis was based on specimens collected from 80 newly diagnosed and 32
      refractory patients with cHL, including longitudinal samples collected under ABVD
      (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy and longitudinal
      samples from relapsing patients treated with chemotherapy and immunotherapy.
      ctDNA mirrored Hodgkin and Reed-Sternberg cell genetics, thus establishing ctDNA
      as an easily accessible source of tumor DNA for cHL genotyping. By identifying
      STAT6 as the most frequently mutated gene in ~40% of cases, we refined the
      current knowledge of cHL genetics. Longitudinal ctDNA profiling identified
      treatment-dependent patterns of clonal evolution in patients relapsing after
      chemotherapy and patients maintained in partial remission under immunotherapy. By
      measuring ctDNA changes during therapy, we propose ctDNA as a radiation-free tool
      to track residual disease that may integrate positron emission tomography imaging
      for the early identification of chemorefractory patients with cHL. Collectively,
      our results provide the proof of concept that ctDNA may serve as a novel
      precision medicine biomarker in cHL.

PMID- 29449277
TI  - Modeling Early Postnatal Brain Growth and Development with CT: Changes in the
      Brain Radiodensity Histogram from Birth to 2 Years.
AB  - BACKGROUND AND PURPOSE: The majority of brain growth and development occur in the
      first 2 years of life. This study investigated these changes by analysis of the
      brain radiodensity histogram of head CT scans from the clinical population, 0-2
      years of age. MATERIALS AND METHODS: One hundred twenty consecutive head CTs with
      normal findings meeting the inclusion criteria from children from birth to 2
      years were retrospectively identified from 3 different CT scan platforms.
      Histogram analysis was performed on brain-extracted images, and histogram mean,
      mode, full width at half maximum, skewness, kurtosis, and SD were correlated with
      subject age. The effects of scan platform were investigated. Normative curves
      were fitted by polynomial regression analysis. RESULTS: Average total brain
      volume was 360 cm3 at birth, 948 cm3 at 1 year, and 1072 cm3 at 2 years. Total
      brain tissue density showed an 11% increase in mean density at 1 year and 19% at
      2 years. Brain radiodensity histogram skewness was positive at birth, declining
      logarithmically in the first 200 days of life. The histogram kurtosis also
      decreased in the first 200 days to approach a normal distribution. Direct
      segmentation of CT images showed that changes in brain radiodensity histogram
      skewness correlated with, and can be explained by, a relative increase in gray
      matter volume and an increase in gray and white matter tissue density that occurs
      during this period of brain maturation. CONCLUSIONS: Normative metrics of the
      brain radiodensity histogram derived from routine clinical head CT images can be
      used to develop a model of normal brain development.

PMID- 29449276
TI  - Immune evasion via PD-1/PD-L1 on NK cells and monocyte/macrophages is more
      prominent in Hodgkin lymphoma than DLBCL.
AB  - Much focus has been on the interaction of programmed cell death ligand 1 (PD-L1)
      on malignant B cells with programmed cell death 1 (PD-1) on effector T cells in
      inhibiting antilymphoma immunity. We sought to establish the contribution of
      natural killer (NK) cells and inhibitory CD163+ monocytes/macrophages in Hodgkin
      lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). Levels of PD-1 on NK
      cells were elevated in cHL relative to DLBCL. Notably, CD3-CD56hiCD16-ve NK cells
      had substantially higher PD-1 expression relative to CD3-CD56dimCD16+ cells and
      were expanded in blood and tissue, more marked in patients with cHL than patients
      with DLBCL. There was also a raised population of PD-L1-expressing CD163+
      monocytes that was more marked in patients with cHL compared with patients with
      DLBCL. The phenotype of NK cells and monocytes reverted back to normal once
      therapy (ABVD [doxorubicin 25 mg/m2, bleomycin 10 000 IU/m2, vinblastine 6 mg/m2,
      dacarbazine 375 mg/m2, all given days 1 and 15, repeated every 28 days] or R-CHOP
      [rituximab 375 mg/m2, cyclophosphamide 750 mg/m2 IV, doxorubicin 50 mg/m2 IV,
      vincristine 1.4 mg/m2 (2 mg maximum) IV, prednisone 100 mg/day by mouth days 1-5,
      pegfilgrastim 6 mg subcutaneously day 4, on a 14-day cycle]) had commenced. Tumor
      associated macrophages (TAMs) expressed high levels of PD-L1/PD-L2 within
      diseased lymph nodes. Consistent with this, CD163/PD-L1/PD-L2 gene expression was
      also elevated in cHL relative to DLBCL tissues. An in vitro functional model of
      TAM-like monocytes suppressed activation of PD-1hi NK cells, which was reversed
      by PD-1 blockade. In line with these findings, depletion of circulating monocytes
      from the blood of pretherapy patients with cHL and patients with DLBCL enhanced
      CD3-CD56hiCD16-ve NK-cell activation. We describe a hitherto unrecognized immune
      evasion strategy mediated via skewing toward an exhausted PD-1-enriched CD3
      CD56hiCD16-ve NK-cell phenotype. In addition to direct inhibition of NK cells by
      the malignant B cell, suppression of NK cells can occur indirectly by PD-L1/PD-L2
      expressing TAMs. The mechanism is more prominent in cHL than DLBCL, which may
      contribute to the clinical sensitivity of cHL to PD-1 blockade.

PMID- 29449279
TI  - MRI with DWI for the Detection of Posttreatment Head and Neck Squamous Cell
      Carcinoma: Why Morphologic MRI Criteria Matter.
AB  - BACKGROUND AND PURPOSE: Although diffusion-weighted imaging combined with
      morphologic MRI (DWIMRI) is used to detect posttreatment recurrent and second
      primary head and neck squamous cell carcinoma, the diagnostic criteria used so
      far have not been clarified. We hypothesized that precise MRI criteria based on
      signal intensity patterns on T2 and contrast-enhanced T1 complement DWI and
      therefore improve the diagnostic performance of DWIMRI. MATERIALS AND METHODS: We
      analyzed 1.5T MRI examinations of 100 consecutive patients treated with radiation
      therapy with or without additional surgery for head and neck squamous cell
      carcinoma. MRI examinations included morphologic sequences and DWI (b=0 and
      b=1000 s/mm2). Histology and follow-up served as the standard of reference. Two
      experienced readers, blinded to clinical/histologic/follow-up data, evaluated
      images according to clearly defined criteria for the diagnosis of recurrent head
      and neck squamous cell carcinoma/second primary head and neck squamous cell
      carcinoma occurring after treatment, post-radiation therapy inflammatory edema,
      and late fibrosis. DWI analysis included qualitative (visual) and quantitative
      evaluation with an ADC threshold. RESULTS: Recurrent head and neck squamous cell
      carcinoma/second primary head and neck squamous cell carcinoma occurring after
      treatment was present in 36 patients, whereas 64 patients had post-radiation
      therapy lesions only. The Cohen kappa for differentiating tumor from post
      radiation therapy lesions with MRI and qualitative DWIMRI was 0.822 and 0.881,
      respectively. Mean ADCmean in recurrent head and neck squamous cell
      carcinoma/second primary head and neck squamous cell carcinoma occurring after
      treatment (1.097 +/- 0.295 * 10-3 mm2/s) was significantly lower (P < .05) than
      in post-radiation therapy inflammatory edema (1.754 +/- 0.343 * 10-3 mm2/s);
      however, it was similar to that in late fibrosis (0.987 +/- 0.264 * 10-3 mm2/s, P
      > .05). Although ADCs were similar in tumors and late fibrosis, morphologic MRI
      criteria facilitated distinction between the 2 conditions. The sensitivity,
      specificity, positive and negative predictive values, and positive and negative
      likelihood ratios (95% CI) of DWIMRI with ADCmean < 1.22 * 10-3 mm2/s and precise
      MRI criteria were 92.1% (83.5-100.0), 95.4% (90.3-100.0), 92.1% (83.5-100.0),
      95.4% (90.2-100.0), 19.9 (6.58-60.5), and 0.08 (0.03-0.24), respectively,
      indicating a good diagnostic performance to rule in and rule out disease.
      CONCLUSIONS: Adding precise morphologic MRI criteria to quantitative DWI enables
      reproducible and accurate detection of recurrent head and neck squamous cell
      carcinoma/second primary head and neck squamous cell carcinoma occurring after
      treatment.

PMID- 29449278
TI  - 7T Brain MRS in HIV Infection: Correlation with Cognitive Impairment and
      Performance on Neuropsychological Tests.
AB  - BACKGROUND AND PURPOSE: Validated neuroimaging markers of HIV-associated
      neurocognitive disorder in patients on antiretroviral therapy are urgently needed
      for clinical trials. The purpose of this study was to explore the relationship
      between cognitive impairment and brain metabolism in older subjects with HIV
      infection. It was hypothesized that MR spectroscopy measurements related to
      neuronal health and function (particularly N-acetylaspartate and glutamate) would
      be lower in HIV-positive subjects with worse cognitive performance. MATERIALS AND
      METHODS: Forty-five HIV-positive patients (mean age, 58.9 +/- 5.3 years; 33 men)
      underwent detailed neuropsychological testing and brain MR spectroscopy at 7T.
      Twenty-four subjects were classified as having asymptomatic cognitive impairment,
      and 21 were classified as having symptomatic cognitive impairment. Single-voxel
      proton MR spectra were acquired from 5 brain regions and quantified using LCModel
      software. Brain metabolites and neuropsychological test results were compared
      using nonparametric statistics and Pearson correlation coefficients. RESULTS:
      Differences in brain metabolites were found between symptomatic and asymptomatic
      subjects, with the main findings being lower measures of N-acetylaspartate in the
      frontal white matter, posterior cingulate cortex, and precuneus. In the
      precuneus, glutamate was also lower in the symptomatic group. In the frontal
      white matter, precuneus, and posterior cingulate cortex, NAA and glutamate
      measurements showed significant positive correlation with better performance on
      neuropsychological tests. CONCLUSIONS: Compared with asymptomatic subjects,
      symptomatic HIV-positive subjects had lower levels of NAA and glutamate, most
      notably in the frontal white matter, which also correlated with performance on
      neuropsychological tests. High-field MR spectroscopy offers insight into the
      pathophysiology associated with cognitive impairment in HIV and may be useful as
      a quantitative outcome measure in future treatment trials.

PMID- 29449280
TI  - Prediction of the Multisegment Clot Sign on Dynamic CT Angiography of
      Cardioembolic Stroke.
AB  - BACKGROUND AND PURPOSE: The multisegment clot sign has been observed at the site
      of large-artery occlusion in patients with acute ischemic stroke. This study
      aimed to assess its occurrence rate and relationship with stroke etiologies in
      patients with acute intracranial large-artery occlusion. MATERIALS AND METHODS:
      We included consecutive patients with acute ischemic stroke who had acute
      intracranial large-artery occlusion and underwent perfusion CT within 8 hours
      after stroke onset. The multisegment clot sign was assessed on dynamic CT
      angiography derived from perfusion CT. The stroke etiologies were defined by the
      international Trial of Org 10172 in Acute Stroke Treatment criteria. Poisson
      regression analyses and diagnostic testing were used to investigate the
      relationship between the multisegment clot sign and stroke etiologies. RESULTS:
      Finally, 194 patients with intracranial large-artery occlusion were enrolled.
      According to the Trial of Org 10172 in Acute Stroke Treatment criteria, 110
      (56.7%) patients were diagnosed with cardioembolism; 43 (22.2%), with large
      artery atherosclerosis; and 41 (21.1%), with undetermined etiology. The
      multisegment clot sign was found in 74 (38%) patients. Poisson regression
      analysis showed that the presence of the multisegment clot sign was significantly
      higher in patients with cardioembolism than in those with large-artery
      atherosclerosis (52.7% versus 9.3%; prevalence ratio, 1.53; 95% confidence
      interval, 1.03-2.90; P = .037). For determined etiologies, the sensitivity,
      specificity, and positive and negative predictive values of the multisegment clot
      sign for predicting cardioembolism were 52.7%, 90.7%, 93.5%, and 42.9%,
      respectively. CONCLUSIONS: The presence of the multisegment clot sign on dynamic
      CTA specifically indicates intracranial large-artery occlusion caused by an
      embolism from a cardiac source, which may be useful for acute management and
      secondary prevention of stroke.

PMID- 29449281
TI  - MRI Features of Aquaporin-4 Antibody-Positive Longitudinally Extensive Transverse
      Myelitis: Insights into the Diagnosis of Neuromyelitis Optica Spectrum Disorders.
AB  - BACKGROUND AND PURPOSE: Longitudinally extensive transverse myelitis is a well
      documented spinal manifestation of neuromyelitis optica spectrum disorders,
      however, other forms of nontumorous myelopathy can also manifest as
      longitudinally extensive transverse myelitis. Our aim was to evaluate the MR
      imaging features of aquaporin-4 antibody-positive longitudinally extensive
      transverse myelitis, which is strongly associated with neuromyelitis optica
      spectrum disorders. MATERIALS AND METHODS: We evaluated cervicomedullary junction
      involvement, cord expansion ratios, bright spotty lesions, the number of involved
      segments, skipped lesions, enhancement patterns, and axial distribution patterns
      using spinal MR imaging of 41 patients with longitudinally extensive transverse
      myelitis who underwent aquaporin-4 antibody testing. Univariate logistic
      regression analysis was performed to identify factors associated with aquaporin-4
      antibody seropositivity, which were then used to develop a scoring system for
      diagnosing aquaporin-4 antibody-positive longitudinally extensive transverse
      myelitis. Interrater reliability for cord expansion ratio measurement and bright
      spotty lesions was determined using intraclass correlation coefficients and kappa
      values, respectively. RESULTS: Fifteen patients with longitudinally extensive
      transverse myelitis were aquaporin-4 antibody-positive. Sex (female),
      cervicomedullary junction involvement, a cord expansion ratio of >1.4, and bright
      spotty lesions were significantly associated with aquaporin-4 antibody
      seropositivity. The sensitivity and specificity of the scoring system were 73.3%
      and 96.2%, respectively. The interclass correlation value for the cord expansion
      ratio was 0.78, and the kappa value for bright spotty lesions was 0.61.
      CONCLUSIONS: Our scoring system, based on cervicomedullary junction involvement,
      higher cord expansion ratio, bright spotty lesions, and female sex, can
      facilitate the timely diagnosis of neuromyelitis optica spectrum disorders.

PMID- 29449283
TI  - Clinical Validation of a Predictive Model for the Presence of Cervical Lymph Node
      Metastasis in Papillary Thyroid Cancer.
AB  - BACKGROUND AND PURPOSE: Ultrasound is a standard technique to detect lymph node
      metastasis in papillary thyroid cancer. Cystic changes and microcalcifications
      are the most specific features of metastasis, but with low sensitivity. This
      prospective study compared the diagnostic accuracy of a predictive model for
      sonographic evaluation of lymph nodes relative to the radiologist's standard
      assessment in detecting papillary thyroid cancer metastasis in patients after
      thyroidectomy. MATERIALS AND METHODS: Cervical lymph node sonographic images were
      reported by a radiologist (R method) per standard practice. The same images were
      independently evaluated by another radiologist using a sonographic predictive
      model (M method). A test was considered positive for metastasis if the R or M
      method suggested lymph node biopsy. The result of lymph node biopsy or surgical
      pathology was used as the reference standard. We estimated relative true-positive
      fraction and relative false-positive fraction using log-linear models for
      correlated binary data for the M method compared with the R method. RESULTS: A
      total of 237 lymph nodes in 103 patients were evaluated. Our analysis of relative
      true-positive fraction and relative false-positive fraction included 54 nodes
      with pathologic results in which at least 1 method (R or M) was positive. The M
      method had a higher relative true-positive fraction of 1.46 (95% CI, 1.12-1.91; P
      = .006) and a lower relative false-positive fraction of 0.58 (95% CI, 0.36-0.92;
      P = .02) compared with the R method. CONCLUSIONS: The sonographic predictive
      model outperformed the standard assessment to detect lymph node metastasis in
      patients with papillary thyroid cancer and may reduce unnecessary biopsies.

PMID- 29449284
TI  - Reply.

PMID- 29449282
TI  - A Patient Dose-Reduction Technique for Neuroendovascular Image-Guided
      Interventions: Image-Quality Comparison Study.
AB  - BACKGROUND AND PURPOSE: The ROI-dose-reduced intervention technique represents an
      extension of ROI fluoroscopy combining x-ray entrance skin dose reduction with
      spatially different recursive temporal filtering to reduce excessive image noise
      in the dose-reduced periphery in real-time. The aim of our study was to compare
      the image quality of simulated neurointerventions with regular and reduced
      radiation doses using a standard flat panel detector system. MATERIALS AND
      METHODS: Ten 3D-printed intracranial aneurysm models were generated on the basis
      of a single patient vasculature derived from intracranial DSA and CTA. The
      incident dose to each model was reduced using a 0.7-mm-thick copper attenuator
      with a circular ROI hole (10-mm diameter) in the middle mounted inside the
      Infinix C-arm. Each model was treated twice with a primary coiling intervention
      using ROI-dose-reduced intervention and regular-dose intervention protocols.
      Eighty images acquired at various intervention stages were shown twice to 2
      neurointerventionalists who independently scored imaging qualities (visibility of
      aneurysm-parent vessel morphology, associated vessels, and/or devices used). Dose
      reduction measurements were performed using an ionization chamber. RESULTS: A
      total integral dose reduction of 62% per frame was achieved. The mean scores for
      regular-dose intervention and ROI dose-reduced intervention images did not differ
      significantly, suggesting similar image quality. Overall intrarater agreement for
      all scored criteria was substantial (Kendall tau = 0.62887; P < .001). Overall
      interrater agreement for all criteria was fair (kappa = 0.2816; 95% CI, 0.2060
      0.3571). CONCLUSIONS: Substantial dose reduction (62%) with a live peripheral
      image was achieved without compromising feature visibility during
      neuroendovascular interventions.

PMID- 29449285
TI  - Relationship between Ischemic Injury and Patient Outcomes after Surgical or
      Endovascular Treatment of Ruptured Anterior Communicating Artery Aneurysms.

PMID- 29449286
TI  - Doctors working for medical defence organisation face redundancy.

PMID- 29449287
TI  - Global Influenza Hospital-based Surveillance Network (GIHSN): results of
      surveillance of influenza and other respiratory viruses in hospitalised patients
      in Brazil, 2015.
AB  - BACKGROUND: Influenza-like illness occurs annually worldwide, with peak timing
      and severity varying seasonally, resulting in significant annual mortality.
      OBJECTIVES: There were three objectives: (1) to describe the epidemiological and
      clinical features of hospitalised patients with severe acute respiratory
      infection caused by influenza and other respiratory viruses (ORVs); (2) to report
      the influenza seasonality in the region and (3) to correlate findings of
      influenza circulation and immunisation time in Brazil. PATIENTS/METHODS: This
      study took place in three Brazilian hospitals located in cities with different
      climatic conditions (Curitiba (south), Rio de Janeiro (south-east) and Fortaleza
      (north-east)). Patients presenting with an acute process with indication for
      admission consisting of a predefined set of conditions potentially associated
      with recent influenza infection were enrolled. RESULTS: We screened 1666
      patients, with 595 meeting the inclusion criteria. Influenza viruses and ORVs
      were detected in 6.5% and 59% of patients, respectively. Influenza-positive cases
      fell into the severe spectrum as compared with those with ORVs (30% vs 11%), but
      without any difference in mortality rates. Epidemiological results revealed
      variations in the peak time of influenza infections between north-east
      (Fortaleza) and south (Curitiba) Brazil, basically following the rain period of
      each region. In north-east Brazil, viral circulation was prevalent in the first 4
      months of the year, indicating that the vaccination campaign occurred in a
      postseasonal period, possibly explaining the low effectiveness. CONCLUSIONS: The
      active-surveillance model is a valuable tool for investigating respiratory virus
      impact on hospitalised patients, with influenza-infection monitoring enabling
      implementation of adequate preventive measures.

PMID- 29449288
TI  - Comparing video consultation with inperson assessment for Swedish patients with
      hard-to-heal ulcers: registry-based studies of healing time and of waiting time.
AB  - OBJECTIVES: To investigate differences in ulcer healing time and waiting time
      between video consultation and inperson assessment for patients with hard-to-heal
      ulcers. SETTING: Patients treated at Blekinge Wound Healing Centre, a primary
      care centre covering the whole of Blekinge county (150 000 inhabitants), were
      compared with patients registered and treated according to the Registry of Ulcer
      Treatment, a Swedish national web-based quality registry. PARTICIPANTS: In the
      study for analysing ulcer healing time, the study group consisted of 100 patients
      diagnosed through video consultation between October 2014 and September 2016. The
      control group for analysing healing time consisted of 1888 patients diagnosed
      through inperson assessment during the same period. In the study for analysing
      waiting time, the same study group (n=100) was compared with 100 patients
      diagnosed through inperson assessment. PRIMARY AND SECONDARY OUTCOME MEASURES:
      Differences in ulcer healing time were analysed using the log-rank test.
      Differences in waiting time were analysed using the Mann-Whitney U test. RESULTS:
      Median healing time was 59 days (95% CI 40 to 78) in the study group and 82 days
      (95% CI 75 to 89) in the control group (P<0.001). Median waiting time was 25 days
      (range: 1-83 days) in the study group and 32 days (range: 3-294 days) for
      patients diagnosed through inperson assessment (P=0.017). There were no
      significant differences between the study group and the control group regarding
      age, gender or ulcer size. CONCLUSIONS: Healing time and waiting time were
      significantly shorter for patients diagnosed through video consultation compared
      with those diagnosed through inperson assessment.

PMID- 29449289
TI  - Linkage of Maternity Hospital Episode Statistics data to birth registration and
      notification records for births in England 2005-2014: methods. A population-based
      birth cohort study.
AB  - INTRODUCTION: Maternity Hospital Episode Statistics (HES) data for 2005-2014 were
      linked to birth registration and birth notification data (previously known as NHS
      Numbers for Babies or NN4B) to bring together some key demographic and clinical
      data items not otherwise available at a national level. The linkage algorithm
      that was previously used to link 2005-2007 data was revised to improve the
      linkage rate and reduce the number of duplicate HES records. METHODS: Birth
      registration and notification linked records from the Office for National
      Statistics ('ONS birth records') were further linked to Maternity HES delivery
      and birth records using the NHS Number and other direct identifiers if the NHS
      Number was missing. RESULTS: For the period 2005-2014, over 94% of birth
      registration and notification records were correctly linked to HES delivery
      records. Two per cent of the ONS birth records were incorrectly linked to the HES
      delivery record and 5% of ONS birth records were linked to more than one HES
      delivery record. Therefore, a considerable amount of time was spent in quality
      assuring these files. CONCLUSION: The linkage rate for birth registration and
      notification records to HES delivery records steadily improved from 2005 to 2014
      due to improvement in the quality and completeness of patient identifiers in both
      HES and birth notification data.

PMID- 29449290
TI  - Community-based rehabilitation training after stroke: results of a pilot
      randomised controlled trial (ReTrain) investigating acceptability and
      feasibility.
AB  - OBJECTIVES: To assess acceptability and feasibility of trial processes and the
      Rehabilitation Training (ReTrain) intervention including an assessment of
      intervention fidelity. DESIGN: A two-group, assessor-blinded, randomised
      controlled trial with parallel mixed methods process and economic evaluations.
      SETTING: Community settings across two sites in Devon. PARTICIPANTS: Eligible
      participants were: 18 years old or over, with a diagnosis of stroke and with self
      reported mobility issues, no contraindications to physical activity, discharged
      from National Health Service or any other formal rehabilitation programme at
      least 1 month before, willing to be randomised to either control or ReTrain and
      attend the training venue, possessing cognitive capacity and communication
      ability sufficient to participate. Participants were individually randomised
      (1:1) via a computer-generated randomisation sequence minimised for time since
      stroke and level of functional disability. Only outcome assessors independent of
      the research team were blinded to group allocation. INTERVENTIONS: ReTrain
      comprised (1) an introductory one-to-one session; (2) ten, twice-weekly group
      classes with up to two trainers and eight clients; (3) a closing one-to-one
      session, followed by three drop-in sessions over the subsequent 3 months.
      Participants received a bespoke home-based training programme. All participants
      received treatment as usual. The control group received an exercise after stroke
      advice booklet. OUTCOME MEASURES: Candidate primary outcomes included functional
      mobility and physical activity. RESULTS: Forty-five participants were randomised
      (ReTrain=23; Control=22); data were available from 40 participants at 6 months of
      follow-up (ReTrain=21; Control=19) and 41 at 9 months of follow-up (ReTrain=21;
      Control=20). We demonstrated ability to recruit and retain participants.
      Participants were not burdened by the requirements of the study. We were able to
      calculate sample estimates for candidate primary outcomes and test procedures for
      process and health economic evaluations. CONCLUSIONS: All objectives were
      fulfilled and indicated that a definitive trial of ReTrain is feasible and
      acceptable. TRIAL REGISTRATION NUMBER: NCT02429180; Results.

PMID- 29449291
TI  - Adapting and enhancing PAX Good Behavior Game for First Nations communities: a
      mixed-methods study protocol developed with Swampy Cree Tribal Council
      communities in Manitoba.
AB  - INTRODUCTION: High rates of mental health problems, such as suicidal behaviours,
      among First Nations youth in Canada are a major public health concern. The Good
      Behavior Game (GBG) is a school-based intervention that provides a nurturing
      environment for children and has been shown to promote positive outcomes. PAX
      Good Behavior Game (PAX GBG) is an adaptation and enhancement of the GBG. While
      PAX GBG has been implemented in Indigenous communities, little research exists
      examining the cultural and contextual appropriateness and effectiveness of the
      intervention in First Nations communities. METHODS AND ANALYSIS: The present
      paper describes a protocol of the mixed-methods approach guided by an Indigenous
      ethical engagement model adopted to implement, adapt and evaluate PAX GBG in
      First Nations communities in Manitoba, Canada. First, implementation outcomes
      (eg, acceptability, adoption) of PAX GBG will be evaluated using qualitative
      interviews with teachers, principals and community members from Swampy Cree
      Tribal Council (SCTC) communities. Second, by linking administrative databases to
      programme data from schools in 38 First Nations communities, we will compare PAX
      GBG and control groups to evaluate whether PAX GBG is associated with improved
      mental health and academic outcomes. Third, the qualitative results will help
      inform a cultural and contextual adaptation of PAX GBG called First Nations PAX
      (FN PAX). Fourth, FN PAX will be implemented in a few SCTC communities and
      evaluated using surveys and qualitative interviews followed by the remaining
      communities the subsequent year. ETHICS AND DISSEMINATION: Ethical approval was
      obtained from the University of Manitoba Health Research Ethics Board and will be
      obtained from the Health Information Privacy Committee and respective data
      providers for the administrative database linkages. Dissemination and knowledge
      translation will include community and stakeholder engagement throughout the
      research process, reports and presentations for policymakers and community
      members, presentations at scientific conferences and journal publications.

PMID- 29449292
TI  - Cost-effectiveness of a community-delivered multicomponent intervention compared
      with enhanced standard care of obese adolescents: cost-utility analysis alongside
      a randomised controlled trial (the HELP trial).
AB  - OBJECTIVE: To undertake a cost-utility analysis of a motivational multicomponent
      lifestyle-modification intervention in a community setting (the Healthy Eating
      Lifestyle Programme (HELP)) compared with enhanced standard care. DESIGN: Cost
      utility analysis alongside a randomised controlled trial. SETTING: Community
      settings in Greater London, England. PARTICIPANTS: 174 young people with obesity
      aged 12-19 years. INTERVENTIONS: Intervention participants received 12 one-to-one
      sessions across 6 months, addressing lifestyle behaviours and focusing on
      motivation to change and self-esteem rather than weight change, delivered by
      trained graduate health workers in community settings. Control participants
      received a single 1-hour one-to-one nurse-delivered session providing didactic
      weight-management advice. MAIN OUTCOME MEASURES: Mean costs and quality-adjusted
      life years (QALYs) per participant over a 1-year period using resource use data
      and utility values collected during the trial. Incremental cost-effectiveness
      ratio (ICER) was calculated and non-parametric bootstrapping was conducted to
      generate a cost-effectiveness acceptability curve (CEAC). RESULTS: Mean
      intervention costs per participant were L918 for HELP and L68 for enhanced
      standard care. There were no significant differences between the two groups in
      mean resource use per participant for any type of healthcare contact. Adjusted
      costs were significantly higher in the intervention group (mean incremental costs
      for HELP vs enhanced standard care L1003 (95% CI L837 to L1168)). There were no
      differences in adjusted QALYs between groups (mean QALYs gained 0.008 (95% CI 
      0.031 to 0.046)). The ICER of the HELP versus enhanced standard care was L120 630
      per QALY gained. The CEAC shows that the probability that HELP was cost-effective
      relative to the enhanced standard care was 0.002 or 0.046, at a threshold of L20
      000 or L30 000 per QALY gained. CONCLUSIONS: We did not find evidence that HELP
      was more effective than a single educational session in improving quality of life
      in a sample of adolescents with obesity. HELP was associated with higher costs,
      mainly due to the extra costs of delivering the intervention and therefore is not
      cost-effective. TRIAL REGISTRATION NUMBER: ISRCTN9984011.

PMID- 29449293
TI  - Feasibility, acceptability and effectiveness of an online alternative to face-to
      face consultation in general practice: a mixed-methods study of webGP in six
      Devon practices.
AB  - OBJECTIVES: To evaluate the feasibility, acceptability and effectiveness of webGP
      as piloted by six general practices. METHODS: Mixed-methods evaluation, including
      data extraction from practice databases, general practitioner (GP) completion of
      case reports, patient questionnaires and staff interviews. SETTING: General
      practices in NHS Northern, Eastern and Western Devon Clinical Commissioning
      Group's area approximately 6 months after implementing webGP (February-July
      2016). PARTICIPANTS: Six practices provided consultations data; 20 GPs completed
      case reports (regarding 61 e-consults); 81 patients completed questionnaires; 5
      GPs and 5 administrators were interviewed. OUTCOME MEASURES: Attitudes and
      experiences of practice staff and patients regarding webGP. RESULTS: WebGP uptake
      during the evaluation was small, showing no discernible impact on practice
      workload. The completeness of cross-sectional data on consultation workload
      varied between practices.GPs judged 41/61 (72%) of webGP requests to require a
      face-to-face or telephone consultation. Introducing webGP appeared to be
      associated with shifts in responsibility and workload between practice staff and
      between practices and patients.81/231 patients completed a postal survey (35.1%
      response rate). E-Consulters were somewhat younger and more likely to be employed
      than face-to-face respondents. WebGP appeared broadly acceptable to patients
      regarding timeliness and quality/experience of care provided. Similar problems
      were presented by all respondents. Both groups appeared equally familiar with
      other practice online services; e-consulters were somewhat more likely to have
      used them.From semistructured staff interviews, it appeared that, while largely
      acceptable within practice, introducing e-consults had potential for adverse
      interactions with pre-existing practice systems. CONCLUSIONS: There is potential
      to assess the impact of new systems on consultation patterns by extracting
      routine data from practice databases. Staff and patients noticed subtle changes
      to responsibilities associated with online options. Greater uptake requires good
      communication between practice and patients, and organisation of systems to avoid
      conflicts and misuse. Further research is required to evaluate the full potential
      of webGP in managing practice workload.

PMID- 29449295
TI  - Management of type 2 diabetes mellitus in people with severe mental illness: an
      online cross-sectional survey of healthcare professionals.
AB  - OBJECTIVES: To establish healthcare professionals' (HCPs) views about clinical
      roles, and the barriers and enablers to delivery of diabetes care for people with
      severe mental illness (SMI). DESIGN: Cross-sectional, postal and online survey.
      SETTING: Trusts within the National Health Service, mental health and diabetes
      charities, and professional bodies. PARTICIPANTS: HCPs who care for people with
      type 2 diabetes mellitus (T2DM) and/or SMI in the UK. PRIMARY AND SECONDARY
      OUTCOME MEASURES: The barriers, enablers and experiences of delivering T2DM care
      for people with SMI, informed by the Theoretical Domains Framework. RESULTS:
      Respondents were 273 HCPs, primarily mental health nurses (33.7%) and
      psychiatrists (32.2%). Only 25% of respondents had received training in managing
      T2DM in people with SMI. Univariate analysis found that mental health
      professionals felt responsible for significantly fewer recommended diabetes care
      standards than physical health professionals (P<0.001). For those seeing diabetes
      care as part of their role, the significant barriers to its delivery in the
      multiple regression analyses were a lack of knowledge (P=0.003); a need for
      training in communication and negotiation skills (P=0.04); a lack of optimism
      about the health of their clients (P=0.04) and their ability to manage T2DM in
      people with SMI (P=0.003); the threat of being disciplined (P=0.02); fear of
      working with people with a mental health condition (P=0.01); a lack of service
      user engagement (P=0.006); and a need for incentives (P=0.04). The significant
      enablers were an understanding of the need to tailor treatments (P=0.04) and
      goals (P=0.02) for people with SMI. CONCLUSIONS: This survey indicates that
      despite current guidelines, diabetes care in mental health settings remains
      peripheral. Even when diabetes care is perceived as part of an HCP's role,
      various individual and organisational barriers to delivering recommended T2DM
      care standards to people with SMI are experienced.

PMID- 29449294
TI  - Disease characteristics and management of hospitalised adolescents and adults
      with community-acquired pneumonia in China: a retrospective multicentre survey.
AB  - OBJECTIVES: To describe the clinical characteristics and management of patients
      hospitalised with community-acquired pneumonia (CAP) in China. DESIGN: This was a
      multicentre, retrospective, observational study. SETTING: 13 teaching hospitals
      in northern, central and southern China from 1 January 2014 to 31 December 2014
      PARTICIPANTS: Information on hospitalised patients aged >=14 years with
      radiographically confirmed pneumonia with illness onset in the community was
      collected using standard case report forms. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Resource use for CAP management. RESULTS: Of 14 793 patients screened,
      5828 with radiographically confirmed CAP were included in the final analysis. Low
      mortality risk patients with a CURB-65 score 0-1 and Pneumonia Severity Index
      risk class I-II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients,
      respectively. 21.7% (1111/5130) patients had already achieved clinical stability
      on admission. A definite or probable pathogen was identified only in 12.7%
      (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection
      risk factors received antimicrobial overtreatment regimens. The median duration
      between clinical stability to discharge was 5.0 days with 30-day mortality of
      4.2%. CONCLUSIONS: These data demonstrated the overuse of health resources in CAP
      management, indicating that there is potential for improvement and substantial
      savings to healthcare systems in China. TRIAL REGISTRATION NUMBER: NCT02489578;
      Results.

PMID- 29449296
TI  - GP and parent dissonance about the assessment and treatment of childhood eczema
      in primary care: a qualitative study.
AB  - OBJECTIVES: To compare parents' and clinicians' perspectives on the assessment
      and treatment of children with eczema in primary care. DESIGN: Qualitative
      interview study with purposive and snowball sampling and thematic analysis.
      SETTING: 14 general practices in the UK. PARTICIPANTS: 11 parents of children
      with eczema and 15 general practitioners (GPs) took part in semistructured
      individual interviews. RESULTS: We identified several areas of dissonance between
      parents and GPs. First, parents sought a 'cause' of eczema, such as an underlying
      allergy, whereas GPs looked to manage the symptoms of an incurable condition.
      Second, parents often judged eczema severity in terms of psychosocial impact,
      while GPs tended to focus on the appearance of the child's skin. Third, parents
      sought 'more natural' over-the-counter treatments or complementary medicine,
      which GPs felt unable to endorse because of their unknown effectiveness and
      potential harm. Fourth, GPs linked poor outcomes to unrealistic expectations of
      treatment and low adherence to topical therapy, whereas parents reported
      persisting with treatment and despondency with its ineffectiveness. Consultations
      were commonly described by parents as being dominated by the GP, with a lack of
      involvement in treatment decisions. GPs' management of divergent views varied,
      but avoidance strategies were often employed. CONCLUSIONS: Divergent views
      between parents and clinicians regarding the cause and treatment of childhood
      eczema can probably only be bridged by clinicians actively seeking out opinions
      and sharing rationale for their approach to treatment. Together with assessing
      the psychosocial as well as the physical impact of eczema, asking about current
      or intended use of complementary therapy and involving parents in treatment
      decisions, the management of eczema and patient outcomes could be improved.

PMID- 29449299
TI  - Burning issues for 2018: long term funding of the NHS.

PMID- 29449297
TI  - Delivering safe and effective test-result communication, management and follow
      up: a mixed-methods study protocol.
AB  - INTRODUCTION: The failure to follow-up pathology and medical imaging test results
      poses patient-safety risks which threaten the effectiveness, quality and safety
      of patient care. The objective of this project is to: (1) improve the
      effectiveness and safety of test-result management through the establishment of
      clear governance processes of communication, responsibility and accountability;
      (2) harness health information technology (IT) to inform and monitor test-result
      management; (3) enhance the contribution of consumers to the establishment of
      safe and effective test-result management systems. METHODS AND ANALYSIS: This
      convergent mixed-methods project triangulates three multistage studies at seven
      adult hospitals and one paediatric hospital in Australia.Study 1 adopts
      qualitative research approaches including semistructured interviews, focus groups
      and ethnographic observations to gain a better understanding of test-result
      communication and management practices in hospitals, and to identify patient
      safety risks which require quality-improvement interventions.Study 2 analyses
      linked sets of routinely collected healthcare data to examine critical test
      result thresholds and test-result notification processes. A controlled before-and
      after study across three emergency departments will measure the impact of
      interventions (including the use of IT) developed to improve the safety and
      quality of test-result communication and management processes.Study 3 adopts a
      consumer-driven approach, including semistructured interviews, and the convening
      of consumer-reference groups and community forums. The qualitative data will
      identify mechanisms to enhance the role of consumers in test-management
      governance processes, and inform the direction of the research and the
      interpretation of findings. ETHICS AND DISSEMINATION: Ethical approval has been
      granted by the South Eastern Sydney Local Health District Human Research Ethics
      Committee and Macquarie University. Findings will be disseminated in academic,
      industry and consumer journals, newsletters and conferences.

PMID- 29449300
TI  - Distinct miRNA profile in prognosis of early CTCL.

PMID- 29449298
TI  - Clinical validation of a public health policy-making platform for hearing loss
      (EVOTION): protocol for a big data study.
AB  - INTRODUCTION: The holistic management of hearing loss (HL) requires an
      understanding of factors that predict hearing aid (HA) use and benefit beyond the
      acoustics of listening environments. Although several predictors have been
      identified, no study has explored the role of audiological, cognitive,
      behavioural and physiological data nor has any study collected real-time HA data.
      This study will collect 'big data', including retrospective HA logging data,
      prospective clinical data and real-time data via smart HAs, a mobile application
      and biosensors. The main objective is to enable the validation of the EVOTION
      platform as a public health policy-making tool for HL. METHODS AND ANALYSIS: This
      will be a big data international multicentre study consisting of retrospective
      and prospective data collection. Existing data from approximately 35 000 HA users
      will be extracted from clinical repositories in the UK and Denmark. For the
      prospective data collection, 1260 HA candidates will be recruited across four
      clinics in the UK and Greece. Participants will complete a battery of
      audiological and other assessments (measures of patient-reported HA benefit,
      mood, cognition, quality of life). Patients will be offered smart HAs and a
      mobile phone application and a subset will also be given wearable biosensors, to
      enable the collection of dynamic real-life HA usage data. Big data analytics will
      be used to detect correlations between contextualised HA usage and effectiveness,
      and different factors and comorbidities affecting HL, with a view to informing
      public health decision-making. ETHICS AND DISSEMINATION: Ethical approval was
      received from the London South East Research Ethics Committee (17/LO/0789), the
      Hippokrateion Hospital Ethics Committee (1847) and the Athens Medical Center's
      Ethics Committee (KM140670). Results will be disseminated through national and
      international events in Greece and the UK, scientific journals, newsletters,
      magazines and social media. Target audiences include HA users, clinicians, policy
      makers and the general public. TRIAL REGISTRATION NUMBER: NCT03316287; Pre
      results.

PMID- 29449301
TI  - BRD4: epigenetic origin and target of CTCL.

PMID- 29449303
TI  - Clot structure predicts recurrent thrombosis.

PMID- 29449302
TI  - Only the strong: when antibodies hold on.

PMID- 29449304
TI  - When it rains, it pours.

PMID- 29449305
TI  - Jordans anomaly.

PMID- 29449306
TI  - Genetic landscape of inherited BMF.

PMID- 29449308
TI  - Predicting AID off-targets: A step forward.
AB  - In this issue of JEM, Alvarez-Prado et al. (https://doi.org/10.1084/jem.20171738)
      designed a DNA capture library allowing them to identify 275 genes targeted by
      AID in mouse germinal center B cells. Using the molecular features of these genes
      to feed a machine-learning algorithm, they determined that high-density RNA PolII
      and Spt5 binding-found in 2.3% of the genes-are the best predictors of AID
      specificity.

PMID- 29449307
TI  - RAGE Deletion Confers Renoprotection by Reducing Responsiveness to Transforming
      Growth Factor-beta and Increasing Resistance to Apoptosis.
AB  - Signaling via the receptor of advanced glycation end products (RAGE)-though
      complex and not fully elucidated in the setting of diabetes-is considered a key
      injurious pathway in the development of diabetic nephropathy (DN). We report here
      that RAGE deletion resulted in increased expression of fibrotic markers (collagen
      I and IV, fibronectin) and the inflammatory marker MCP-1 in primary mouse
      mesangial cells (MCs) and in kidney cortex. RNA sequencing analysis in MCs from
      RAGE-/- and wild-type mice confirmed these observations. Nevertheless, despite
      these gene expression changes, decreased responsiveness to transforming growth
      factor-beta was identified in RAGE-/- mice. Furthermore, RAGE deletion conferred
      a more proliferative phenotype in MCs and reduced susceptibility to staurosporine
      induced apoptosis. RAGE restoration experiments in RAGE-/- MCs largely reversed
      these gene expression changes, resulting in reduced expression of fibrotic and
      inflammatory markers. This study highlights that protection against DN in RAGE
      knockout mice is likely to be due in part to the decreased responsiveness to
      growth factor stimulation and an antiapoptotic phenotype in MCs. Furthermore, it
      extends our understanding of the role of RAGE in the progression of DN, as RAGE
      seems to play a key role in modulating the sensitivity of the kidney to injurious
      stimuli such as prosclerotic cytokines.

PMID- 29449310
TI  - Correction: Critical role for Sec22b-dependent antigen cross-presentation in
      antitumor immunity.

PMID- 29449309
TI  - ZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate
      CD8+ T cell fates.
AB  - Long-term immunity depends partly on the establishment of memory CD8+ T cells. We
      identified a counterregulatory network between the homologous transcription
      factors ZEB1 and ZEB2 and the miR-200 microRNA family, which modulates effector
      CD8+ T cell fates. Unexpectedly, Zeb1 and Zeb2 had reciprocal expression patterns
      and were functionally uncoupled in CD8+ T cells. ZEB2 promoted terminal
      differentiation, whereas ZEB1 was critical for memory T cell survival and
      function. Interestingly, the transforming growth factor beta (TGF-beta) and miR
      200 family members, which counterregulate the coordinated expression of Zeb1 and
      Zeb2 during the epithelial-to-mesenchymal transition, inversely regulated Zeb1
      and Zeb2 expression in CD8+ T cells. TGF-beta induced and sustained Zeb1
      expression in maturing memory CD8+ T cells. Meanwhile, both TGF-beta and miR-200
      family members selectively inhibited Zeb2. Additionally, the miR-200 family was
      necessary for optimal memory CD8+ T cell formation. These data outline a
      previously unknown genetic pathway in CD8+ T cells that controls effector and
      memory cell fate decisions.

PMID- 29449311
TI  - Weekly Versus Daily Dipeptidyl Peptidase 4 Inhibitor Therapy for Type 2 Diabetes:
      Systematic Review and Meta-analysis.

PMID- 29449312
TI  - Prevalence and Prognostic Impact of Diabetes in Takotsubo Syndrome: Insights From
      the International, Multicenter GEIST Registry.
AB  - OBJECTIVE: In view of low prevalence rates, diabetes is discussed as a protective
      factor for the occurrence of Takotsubo syndrome (TTS). Furthermore, it was
      associated with improved outcome in a small single-center analysis. Therefore,
      this study assessed the prevalence and prognostic relevance of concomitant
      diabetes in TTS. RESEARCH DESIGN AND METHODS: A total of 826 patients with TTS
      were enrolled in an international, multicenter, registry-based study (eight
      centers in Italy and Germany). All-cause mortality was compared between patients
      with diabetes and patients without diabetes, and the independent predictive value
      of diabetes was evaluated in multivariate regression analysis. RESULTS: The
      prevalence of diabetes was 21.1% (n = 174). TTS patients with diabetes were older
      (P < 0.001), were more frequently male (P = 0.003), had a higher prevalence of
      hypertension (P < 0.001), physical triggers (P = 0.041), and typical apical
      ballooning (P = 0.010), had a lower left ventricular ejection fraction (P =
      0.008), had a higher rate of pulmonary edema (P = 0.032), and had a longer
      hospital stay (P = 0.009). However, 28-day all-cause mortality did not differ
      between patients with diabetes and patients without diabetes (6.4% vs. 5.7%;
      hazard ratio [HR] 1.11 [95% CI 0.55-2.25]; P = 0.772). Longer-term follow-up
      after a median of 2.5 years revealed a significantly higher mortality among TTS
      patients with diabetes (31.4% vs. 16.5%; P < 0.001), and multivariate regression
      analysis identified diabetes as an independent predictor of adverse outcome (HR
      1.66 [95% CI 1.16-2.39]; P = 0.006). CONCLUSIONS: Diabetes is not uncommon in
      patients with TTS, is associated with increased longer-term mortality rates, and
      is an independent predictor of adverse outcome irrespective of additional risk
      factors.

PMID- 29449313
TI  - Impaired thermogenesis and sharp increases in plasma triglyceride levels in
      GPIHBP1-deficient mice during cold exposure.
AB  - Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
      (GPIHBP1), an endothelial cell protein, binds LPL in the subendothelial spaces
      and transports it to the capillary lumen. In Gpihbp1-/- mice, LPL remains
      stranded in the subendothelial spaces, causing hypertriglyceridemia, but how
      Gpihbp1-/- mice respond to metabolic stress (e.g., cold exposure) has never been
      studied. In wild-type mice, cold exposure increases LPL-mediated processing of
      triglyceride-rich lipoproteins (TRLs) in brown adipose tissue (BAT), providing
      fuel for thermogenesis and leading to lower plasma triglyceride levels. We
      suspected that defective TRL processing in Gpihbp1-/- mice might impair
      thermogenesis and blunt the fall in plasma triglyceride levels. Indeed, Gpihbp1-/
      mice exhibited cold intolerance, but the effects on plasma triglyceride levels
      were paradoxical. Rather than falling, the plasma triglyceride levels increased
      sharply (from ~4,000 to ~15,000 mg/dl), likely because fatty acid release by
      peripheral tissues drives hepatic production of TRLs that cannot be processed. We
      predicted that the sharp increase in plasma triglyceride levels would not occur
      in Gpihbp1-/-Angptl4-/- mice, where LPL activity is higher and baseline plasma
      triglyceride levels are lower. Indeed, the plasma triglyceride levels in Gpihbp1
      /-Angptl4-/- mice fell during cold exposure. Metabolic studies revealed increased
      levels of TRL processing in the BAT of Gpihbp1-/-Angptl4-/- mice.

PMID- 29449316
TI  - SNAREing an ARP requires a LIR.
AB  - The fusion of autophagosomes with lysosomes is an obligatory step in the self
      eating process of autophagy. In this issue, Kumar et al. (2018. J. Cell Biol.
      https://doi.org/10.1083/jcb.201708039) identify a protein complex, the
      autophagosome recognition particle (ARP), that chaperones a key SNARE, syntaxin
      17, to the autophagosome membrane. Intriguingly, this protein complex coordinates
      both delivery and membrane insertion as a prelude to fusion.

PMID- 29449314
TI  - Vitamin D, PCOS and androgens in men: a systematic review.
AB  - BACKGROUND: Accumulating evidence from animal and human studies suggests that
      vitamin D is involved in many functions of the reproductive system in both
      genders. AIM: The aim of this review was to provide an overview on the effects of
      vitamin D on polycystic ovary syndrome (PCOS) in women and androgen metabolism in
      men. METHODS: We performed a systematic literature search in PubMed for relevant
      English language publications published from January 2012 until September 2017.
      RESULTS AND DISCUSSION: The vitamin D receptor and vitamin D-metabolizing enzymes
      are found in reproductive tissues of women and men. In women, vitamin D status
      has been associated with several features of PCOS. In detail, cross-sectional
      data suggest a regulatory role of vitamin D in PCOS-related aspects such as
      ovulatory dysfunction, insulin resistance as well as hyperandrogenism. Moreover,
      results from randomized controlled trials (RCTs) suggest that vitamin D
      supplementation may be beneficial for metabolic, endocrine and fertility aspects
      in PCOS. In men, vitamin D status has been associated with androgen levels and
      hypogonadism. Further, there is some evidence for a favorable effect of vitamin D
      supplementation on testosterone concentrations, although others failed to show a
      significant effect on testosterone levels. CONCLUSION: In summary, vitamin D
      deficiency is associated with adverse fertility outcomes including PCOS and
      hypogonadism, but the evidence is insufficient to establish causality. High
      quality RCTs are needed to further evaluate the effects of vitamin D
      supplementation in PCOS women as well as on androgen levels in men.

PMID- 29449317
TI  - It Takes a Village to Move a Hospital: Simulation Improves Intensive Care Team
      Preparedness for a Move to a New Site.
AB  - OBJECTIVES: To evaluate in-situ simulation to prepare a PICU to move to a new,
      redesigned unit. METHODS: The study setting is an academic PICU. This is a cross
      sectional study using in-situ simulations of common PICU admissions.
      Postsimulation, participants completed a survey comparing the perception of
      preparedness pre- and postsimulation (via a 10-point Likert scale). Participants
      were resurveyed 6 months postmove to assess whether effects persisted.
      Qualitative data were obtained via thematic review of the survey comment section
      and from postsimulation debriefing. RESULTS: Response rates were initially 100%
      and 67% at the 6-month follow-up. In the initial phase, all questions had
      statistically significant improvements in post- versus presimulation scores.
      Participants felt better prepared (presimulation: 6.20, postsimulation: 7.90, P <
      .001) and more confident about caring for real patients (presimulation: 5.49,
      postsimulation: 7.41, P < .001). They felt more comfortable working in the new
      unit (presimulation: 5.65, postsimulation: 7.50, P < .001) and better able to
      deliver safe care (presimulation: 5.85, postsimulation: 7.60, P < .001). Six
      months postmove, participants still believed that simulation was helpful (7.43,
      SD: 2.20) and still reported improved team confidence (7.36, SD: 2.11). Only 1 of
      28 participants preferred less simulation. Exercises were described as helpful in
      identifying process and latent patient safety issues. CONCLUSIONS: Our pediatric
      intensive care team found simulations to be beneficial in preparation for
      providing care to critically ill children in a complex new setting. Simulations
      uncovered latent process, personnel, and patient-safety issues that were
      addressed before actual patient care.

PMID- 29449315
TI  - Metaplastic breast cancer in a patient with neurofibromatosis type 1 and somatic
      loss of heterozygosity.
AB  - Metaplastic breast carcinoma (MBC) is rare and has a poor prognosis. Here we
      describe genetic analysis of a 41-yr-old female patient with MBC and
      neurofibromatosis type I (NF1). She initially presented with pT3N1a, grade 3 MBC,
      but lung metastases were discovered subsequently. To identify the molecular cause
      of her NF1, we screened for germline mutations disrupting NF1 or SPRED1,
      revealing a heterozygous germline single-nucleotide variant (SNV) in exon 21 of
      NF1 at c.2709G>A, Chr 17: 29556342. By report, this variant disrupts pre-mRNA
      splicing of NF1 transcripts. No pathogenic mutations were identified in SPRED1 A
      potential association between MBC and NF1 was reported in eight previous cases,
      but none underwent detailed genomics analysis. To identify additional candidate
      germline variants potentially predisposing to MBC, we conducted targeted exome
      sequencing of 279 established cancer-causing genes in a control blood sample,
      disclosing four rare SNVs. Analysis of her breast tumor showed markedly altered
      variant allelic fractions (VAFs) for two (50%) of them, revealing somatic loss of
      heterozygosity (LOH) at germline SNVs. Of these, only the VAF of the pathogenic
      SNV in NF1 was increased in the tumor. Tumor sequencing demonstrated five somatic
      mutations altering TP53, BRCA1, and other genes potentially contributing to
      cancer formation. Because somatic LOH at certain germline SNVs can enhance their
      impacts, we conclude that increased allelic imbalance of the pathogenic SNV in
      NF1 likely contributed to tumorigenesis. Our results highlight a need to assess
      predisposing genetic factors and LOH that can cause rare, aggressive diseases
      such as MBC in NF1.

PMID- 29449320
TI  - Correction: Regulatory Aspects of Optical Methods and Exogenous Targets for
      Cancer Detection.

PMID- 29449318
TI  - Exosomal microRNA-21-5p Mediates Mesenchymal Stem Cell Paracrine Effects on Human
      Cardiac Tissue Contractility.
AB  - RATIONALE: The promising clinical benefits of delivering human mesenchymal stem
      cells (hMSCs) for treating heart disease warrant a better understanding of
      underlying mechanisms of action. hMSC exosomes increase myocardial contractility;
      however, the exosomal cargo responsible for these effects remains unresolved.
      OBJECTIVE: This study aims to identify lead cardioactive hMSC exosomal microRNAs
      to provide a mechanistic basis for optimizing future stem cell-based
      cardiotherapies. METHODS AND RESULTS: Integrating systems biology and human
      engineered cardiac tissue (hECT) technologies, partial least squares regression
      analysis of exosomal microRNA profiling data predicted microRNA-21-5p (miR-21-5p)
      levels positively correlate with contractile force and calcium handling gene
      expression responses in hECTs treated with conditioned media from multiple cell
      types. Furthermore, miR-21-5p levels were significantly elevated in hECTs treated
      with the exosome-enriched fraction of the hMSC secretome (hMSC-exo) versus
      untreated controls. This motivated experimentally testing the human-specific role
      of miR-21-5p in hMSC-exo-mediated increases of cardiac tissue contractility.
      Treating hECTs with miR-21-5p alone was sufficient to recapitulate effects
      observed with hMSC-exo on hECT developed force and expression of associated
      calcium handling genes (eg, SERCA2a and L-type calcium channel). Conversely,
      knockdown of miR-21-5p in hMSCs significantly diminished exosomal procontractile
      and associated calcium handling gene expression effects on hECTs. Western blots
      supported miR-21-5p effects on calcium handling gene expression at the protein
      level, corresponding to significantly increased calcium transient amplitude and
      decreased decay time constant in comparison to miR-scramble control.
      Mechanistically, cotreating with miR-21-5p and LY294002, a PI3K inhibitor,
      suppressed these effects. Finally, mathematical simulations predicted the
      translational capacity for miR-21-5p treatment to restore calcium handling in
      mature ischemic adult human cardiomyocytes. CONCLUSIONS: miR-21-5p plays a key
      role in hMSC-exo-mediated effects on cardiac contractility and calcium handling,
      likely via PI3K signaling. These findings may open new avenues of research to
      harness the role of miR-21-5p in optimizing future stem cell-based
      cardiotherapies.

PMID- 29449321
TI  - Correction: Integrating Models to Quantify Environment-Mediated Drug Resistance.

PMID- 29449322
TI  - Actin retrograde flow controls natural killer cell response by regulating the
      conformation state of SHP-1.
AB  - Natural killer (NK) cells are a powerful weapon against viral infections and
      tumor growth. Although the actin-myosin (actomyosin) cytoskeleton is crucial for
      a variety of cellular processes, the role of mechanotransduction, the conversion
      of actomyosin mechanical forces into signaling cascades, was never explored in NK
      cells. Here, we demonstrate that actomyosin retrograde flow (ARF) controls the
      immune response of primary human NK cells through a novel interaction between
      beta-actin and the SH2-domain-containing protein tyrosine phosphatase-1 (SHP-1),
      converting its conformation state, and thereby regulating NK cell cytotoxicity.
      Our results identify ARF as a master regulator of the NK cell immune response.
      Since actin dynamics occur in multiple cellular processes, this mechanism might
      also regulate the activity of SHP-1 in additional cellular systems.

PMID- 29449324
TI  - STIM1 (c)AMPs up melanogenesis.

PMID- 29449323
TI  - Structural basis of siRNA recognition by TRBP double-stranded RNA binding
      domains.
AB  - The accurate cleavage of pre-micro(mi)RNAs by Dicer and mi/siRNA guide strand
      selection are important steps in forming the RNA-induced silencing complex
      (RISC). The role of Dicer binding partner TRBP in these processes remains poorly
      understood. Here, we solved the solution structure of the two N-terminal dsRNA
      binding domains (dsRBDs) of TRBP in complex with a functionally asymmetric siRNA
      using NMR, EPR, and single-molecule spectroscopy. We find that siRNA recognition
      by the dsRBDs is not sequence-specific but rather depends on the RNA shape. The
      two dsRBDs can swap their binding sites, giving rise to two equally populated,
      pseudo-symmetrical complexes, showing that TRBP is not a primary sensor of siRNA
      asymmetry. Using our structure to model a Dicer-TRBP-siRNA ternary complex, we
      show that TRBP's dsRBDs and Dicer's RNase III domains bind a canonical 19 base
      pair siRNA on opposite sides, supporting a mechanism whereby TRBP influences
      Dicer-mediated cleavage accuracy by binding the dsRNA region of the pre-miRNA
      during Dicer cleavage.

PMID- 29449325
TI  - Quantitative Flow Ratio Identifies Nonculprit Coronary Lesions Requiring
      Revascularization in Patients With ST-Segment-Elevation Myocardial Infarction and
      Multivessel Disease.
AB  - BACKGROUND: The nonculprit lesion (NCL) management in ST-segment-elevation
      myocardial infarction patients with multivessel disease is debated. We sought to
      assess whether quantitative flow ratio (QFR), a noninvasive tool to identify
      potentially flow-limiting lesions, may be reliable in this scenario. METHODS AND
      RESULTS: The present proof-of-concept study is based on a 3-step process: (1)
      identification of the QFR reproducibility in NCLs assessment (cohort A, n=31);
      (2) prospective validation of QFR diagnostic accuracy in respect to fractional
      flow reserve (cohort B, n=45); and (3) investigation of long-term clinical
      outcomes of NCLs stratified according to QFR (cohort C, n=110). A blinded core
      laboratory computed QFR values for all NCLs. Cohort A showed a good correlation
      and agreement between QFR values at index (acute) and at staged (subacute, 3-4
      days later) procedures (r=0.98; 95% confidence interval, 0.96-0.99; mean
      difference, 0.004 [-0.027 to 0.34]). The inter-rater agreement was kappa=0.9. In
      cohort B, fractional flow reserve and QFR identified 16 (33%) and 17 (35%) NCLs
      potentially flow limiting. Sensitivity, specificity, negative, and positive
      predictive values were 88%, 97%, 94%, and 94%. The area under the receiver
      operating characteristics curve was 0.96 (95% confidence interval, 0.89-0.99).
      Finally, in cohort C, we identified 110 ST-segment-elevation myocardial
      infarction patients where at least 1 NCL was left untreated. Patients with NCLs
      showing a QFR value <=0.80 were at higher risk of adverse events (hazard ratio,
      2.3; 95% confidence interval, 1.2-4.5; P=0.01). CONCLUSIONS: In a limited and
      selected study population, our study showed that QFR computation may be a safe
      and reliable tool to guide coronary revascularization of NCLs in ST-segment
      elevation myocardial infarction patients.

PMID- 29449327
TI  - Kyleena - another levonorgestrel IUS.
AB  - A levonorgestrel (LNG) intrauterine system (IUS) known as Kyleena (Bayer PLC)
      received marketing authorisation from the European Medicines Agency in 2016.1 The
      device contains 19.5mg LNG and is licensed for contraception for up to 5 years.
      This is the fourth LNG IUS product to be licensed for use in the UK. The company
      states that Kyleena offers advantages over Mirena and Jaydess LNG IUS devices.2
      Here we consider the evidence for Kyleena.

PMID- 29449326
TI  - Fatty acid synthase mediates EGFR palmitoylation in EGFR mutated non-small cell
      lung cancer.
AB  - Metabolic reprogramming is widely known as a hallmark of cancer cells to allow
      adaptation of cells to sustain survival signals. In this report, we describe a
      novel oncogenic signaling pathway exclusively acting in mutated epidermal growth
      factor receptor (EGFR) non-small cell lung cancer (NSCLC) with acquired tyrosine
      kinase inhibitor (TKI) resistance. Mutated EGFR mediates TKI resistance through
      regulation of the fatty acid synthase (FASN), which produces 16-C saturated fatty
      acid palmitate. Our work shows that the persistent signaling by mutated EGFR in
      TKI-resistant tumor cells relies on EGFR palmitoylation and can be targeted by
      Orlistat, an FDA-approved anti-obesity drug. Inhibition of FASN with Orlistat
      induces EGFR ubiquitination and abrogates EGFR mutant signaling, and reduces
      tumor growths both in culture systems and in vivo Together, our data provide
      compelling evidence on the functional interrelationship between mutated EGFR and
      FASN and that the fatty acid metabolism pathway is a candidate target for
      acquired TKI-resistant EGFR mutant NSCLC patients.

PMID- 29449328
TI  - Cladribine for multiple sclerosis.
AB  - In the UK, there are twelve disease-modifying drugs licensed for various forms of
      multiple sclerosis (MS), of which three are oral therapies. An oral formulation
      of cladribine (Mavenclad - Merck Serono Europe Limited) was recently licensed by
      the European Medicines Agency (EMA) for the treatment of adult patients with
      highly active relapsing MS.1,2 It is claimed to be "an innovatively simple
      approach" for treating this form of MS and "the only disease modifying therapy
      that can deliver and sustain 4 years of disease control with a maximum of 20 days
      oral treatment in the first 2 years."3 Here, we consider the evidence for its use
      in the treatment of highly active relapsing MS.

PMID- 29449330
TI  - Therapeutic Lowering of Lipoprotein(a): A Role for Pharmacogenetics?

PMID- 29449329
TI  - Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2
      THRIVE Study.
AB  - BACKGROUND: Genetic studies have shown lipoprotein(a) (Lp[a]) to be an important
      causal risk factor for coronary disease. Apolipoprotein(a) isoform size is the
      chief determinant of Lp(a) levels, but its impact on the benefits of therapies
      that lower Lp(a) remains unclear. METHODS: HPS2-THRIVE (Heart Protection Study 2
      Treatment of HDL to Reduce the Incidence of Vascular Events) is a randomized
      trial of niacin-laropiprant versus placebo on a background of simvastatin
      therapy. Plasma Lp(a) levels at baseline and 1 year post-randomization were
      measured in 3978 participants from the United Kingdom and China.
      Apolipoprotein(a) isoform size, estimated by the number of kringle IV domains,
      was measured by agarose gel electrophoresis and the predominantly expressed
      isoform identified. RESULTS: Allocation to niacin-laropiprant reduced mean Lp(a)
      by 12 (SE, 1) nmol/L overall and 34 (6) nmol/L in the top quintile by baseline
      Lp(a) level (Lp[a] >=128 nmol/L). The mean proportional reduction in Lp(a) with
      niacin-laropiprant was 31% but varied strongly with predominant apolipoprotein(a)
      isoform size (PTrend=4*10-29) and was only 18% in the quintile with the highest
      baseline Lp(a) level and low isoform size. Estimates from genetic studies suggest
      that these Lp(a) reductions during the short term of the trial might yield
      proportional reductions in coronary risk of ~2% overall and 6% in the top
      quintile by Lp(a) levels. CONCLUSIONS: Proportional reductions in Lp(a) were
      dependent on apolipoprotein(a) isoform size. Taking this into account, the likely
      benefits of niacin-laropiprant on coronary risk through Lp(a) lowering are small.
      Novel therapies that reduce high Lp(a) levels by at least 80 nmol/L (~40%) may be
      needed to produce worthwhile benefits in people at the highest risk because of
      Lp(a). CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique
      identifier: NCT00461630.

PMID- 29449331
TI  - Lipid-Lowering Therapy With Ezetimibe Decreases Spontaneous Atherothrombotic
      Occlusions in a Rabbit Model of Plaque Erosion: A Role of Serum Oxysterols.
AB  - OBJECTIVE: Plaque erosion is increasing its importance as one of the mechanisms
      of acute coronary syndromes in this statin era. However, the clinical efficacy of
      currently used lipid-lowering agents in the prevention of thrombotic
      complications associated with plaque erosion has not been clarified. Therefore,
      we examined the therapeutic effects of ezetimibe or rosuvastatin monotherapy on
      spontaneous atherothrombotic occlusion. APPROACH AND RESULTS: Femoral arteries of
      Japanese white rabbits, fed a high-cholesterol diet, were injured by balloon
      catheter, and then angiotensin II was continuously administrated. In 94% of these
      arteries, spontaneous thrombotic occlusions were observed after 5 weeks (median)
      of balloon injury. Histochemical analyses indicated that the injured arteries had
      similar pathological features to human plaque erosions; (1) spontaneous
      thrombotic occlusion, (2) lack of endothelial cells, and (3) tissue factor
      expression in vascular smooth muscle cells. Ezetimibe (1.0 mg/kg per day), but
      not rosuvastatin (0.6 mg/kg per day), significantly decreased thrombotic
      occlusion of arteries accompanied with accelerated re-endothelialization and the
      decreases of serum oxysterols despite the comparable on-treatment serum
      cholesterol levels. The 7-ketocholesterol inhibited the migration of human
      umbilical vein endothelial cells. Both 7-ketocholesterol and 27
      hydroxycholesterol increased tissue factor expression in cultured rat vascular
      smooth muscle cells. Tissue factor expression was also induced by serum from
      vehicle- or rosuvastatin-treated rabbits, but the induction was attenuated with
      serum from ezetimibe-treated rabbits. CONCLUSIONS: We have established a novel
      rabbit model of spontaneous atherothromobotic occlusion without plaque rupture
      that is feasible to test the therapeutic effects of various pharmacotherapies.
      Ezetimibe may decrease atherothrombotic complications after superficial plaque
      erosion by reducing serum oxysterols.

PMID- 29449332
TI  - Inhibition of Endothelial NOTCH1 Signaling Attenuates Inflammation by Reducing
      Cytokine-Mediated Histone Acetylation at Inflammatory Enhancers.
AB  - OBJECTIVE: Endothelial upregulation of adhesion molecules serves to recruit
      leukocytes to inflammatory sites and appears to be promoted by NOTCH1; however,
      current models based on interactions between active NOTCH1 and NF-kappaB
      components cannot explain the transcriptional selectivity exerted by NOTCH1 in
      this context. APPROACH AND RESULTS: Observing that Cre/Lox-induced conditional
      mutations of endothelial Notch modulated inflammation in murine contact
      hypersensitivity, we found that IL (interleukin)-1beta stimulation induced rapid
      recruitment of RELA (v-rel avian reticuloendotheliosis viral oncogene homolog A)
      to genomic sites occupied by NOTCH1-RBPJ (recombination signal-binding protein
      for immunoglobulin kappa J region) and that NOTCH1 knockdown reduced histone
      H3K27 acetylation at a subset of NF-kappaB-directed inflammatory enhancers.
      CONCLUSIONS: Our findings reveal that NOTCH1 signaling supports the expression of
      a subset of inflammatory genes at the enhancer level and demonstrate how key
      signaling pathways converge on chromatin to coordinate the transition to an infla
      mmatory endothelial phenotype.

PMID- 29449333
TI  - Endothelial Cell Autonomous Role of Akt1: Regulation of Vascular Tone and
      Ischemia-Induced Arteriogenesis.
AB  - OBJECTIVE: The importance of PI3K/Akt signaling in the vasculature has been
      demonstrated in several models, as global loss of Akt1 results in impaired
      postnatal ischemia- and VEGF-induced angiogenesis. The ubiquitous expression of
      Akt1, however, raises the possibility of cell-type-dependent Akt1-driven actions,
      thereby necessitating tissue-specific characterization. APPROACH AND RESULTS:
      Herein, we used an inducible, endothelial-specific Akt1-deleted adult mouse model
      (Akt1iECKO) to characterize the endothelial cell autonomous functions of Akt1 in
      the vascular system. Endothelial-targeted ablation of Akt1 reduces eNOS
      (endothelial nitric oxide synthase) phosphorylation and promotes both increased
      vascular contractility in isolated vessels and elevated diastolic blood pressures
      throughout the diurnal cycle in vivo. Furthermore, Akt1iECKO mice subject to the
      hindlimb ischemia model display impaired blood flow and decreased arteriogenesis.
      CONCLUSIONS: Endothelial Akt1 signaling is necessary for ischemic resolution post
      injury and likely reflects the consequence of NO insufficiency critical for
      vascular repair.

PMID- 29449334
TI  - RGC-32 (Response Gene to Complement 32) Deficiency Protects Endothelial Cells
      From Inflammation and Attenuates Atherosclerosis.
AB  - OBJECTIVE: The objective of this study is to determine the role and underlying
      mechanisms of RGC-32 (response gene to complement 32 protein) in atherogenesis.
      APPROACH AND RESULTS: RGC-32 was mainly expressed in endothelial cells of
      atherosclerotic lesions in both ApoE-/- (apolipoprotein E deficient) mice and
      human patients. Rgc-32 deficiency (Rgc32-/-) attenuated the high-fat diet-induced
      and spontaneously developed atherosclerotic lesions in ApoE-/- mice without
      affecting serum cholesterol concentration. Rgc32-/- seemed to decrease the
      macrophage content without altering collagen and smooth muscle contents or
      lesional macrophage proliferation in the lesions. Transplantation of WT (wild
      type) mouse bone marrow to lethally irradiated Rgc32-/- mice did not alter Rgc32
      /--caused reduction of lesion formation and macrophage accumulation, suggesting
      that RGC-32 in resident vascular cells, but not the macrophages, plays a critical
      role in the atherogenesis. Of importance, Rgc32-/- decreased the expression of
      ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion
      molecule-1) in endothelial cells both in vivo and in vitro, resulting in a
      decrease in TNF-alpha (tumor necrosis factor-alpha)-induced monocyte-endothelial
      cell interaction. Mechanistically, RGC-32 mediated the ICAM-1 and VCAM-1
      expression, at least partially, through NF (nuclear factor)-kappaB signaling
      pathway. RGC-32 directly interacted with NF-kappaB and facilitated its nuclear
      translocation and enhanced TNF-alpha-induced NF-kappaB binding to ICAM-1 and VCAM
      1 promoters. CONCLUSIONS: RGC-32 mediates atherogenesis by facilitating monocyte
      endothelial cell interaction via the induction of endothelial ICAM-1 and VCAM-1
      expression, at least partially, through NF-kappaB signaling pathway.

PMID- 29449335
TI  - Bempedoic Acid Lowers Low-Density Lipoprotein Cholesterol and Attenuates
      Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient (LDLR+/- and LDLR-/
      ) Yucatan Miniature Pigs.
AB  - OBJECTIVE: Bempedoic acid (BemA; ETC-1002) is a novel drug that targets hepatic
      ATP-citrate lyase to reduce cholesterol biosynthesis. In phase 2 studies, BemA
      lowers elevated low-density lipoprotein cholesterol (LDL-C) in
      hypercholesterolemic patients. In the present study, we tested the ability of
      BemA to decrease plasma cholesterol and LDL-C and attenuate atherosclerosis in a
      large animal model of familial hypercholesterolemia. APPROACH AND RESULTS: Gene
      targeting has been used to generate Yucatan miniature pigs heterozygous (LDLR+/-)
      or homozygous (LDLR-/-) for LDL receptor deficiency (ExeGen). LDLR+/- and LDLR-/-
      pigs were fed a high-fat, cholesterol-containing diet (34% kcal fat; 0.2%
      cholesterol) and orally administered placebo or BemA for 160 days. In LDLR+/-
      pigs, compared with placebo, BemA decreased plasma cholesterol and LDL-C up to
      40% and 61%, respectively. In LDLR-/- pigs, in which plasma cholesterol and LDL-C
      were 5-fold higher than in LDLR+/- pigs, BemA decreased plasma cholesterol and
      LDL-C up to 27% and 29%, respectively. Plasma levels of triglycerides and high
      density lipoprotein cholesterol, fasting glucose and insulin, and liver lipids
      were unaffected by treatment in either genotype. In the aorta of LDLR+/- pigs,
      BemA robustly attenuated en face raised lesion area (-58%) and left anterior
      descending coronary artery cross-sectional lesion area (-40%). In LDLR-/- pigs,
      in which lesions were substantially more advanced, BemA decreased aortic lesion
      area (-47%) and left anterior descending coronary artery lesion area (-48%).
      CONCLUSIONS: In a large animal model of LDLR deficiency and atherosclerosis, long
      term treatment with BemA reduces LDL-C and attenuates the development of aortic
      and coronary atherosclerosis in both LDLR+/- and LDLR-/- miniature pigs.

PMID- 29449336
TI  - Dual Anticoagulant and Antiplatelet Therapy for Coronary Artery Disease and
      Peripheral Artery Disease Patients.

PMID- 29449337
TI  - ALK1 Loss Results in Vascular Hyperplasia in Mice and Humans Through PI3K
      Activation.
AB  - OBJECTIVE: ALK1 (activin-receptor like kinase 1) is an endothelial cell
      restricted receptor with high affinity for BMP (bone morphogenetic protein) 9 TGF
      beta (transforming growth factor-beta) family member. Loss-of-function mutations
      in ALK1 cause a subtype of hereditary hemorrhagic telangiectasia-a rare disease
      characterized by vasculature malformations. Therapeutic strategies are aimed at
      reducing potential complications because of vascular malformations, but
      currently, there is no curative treatment for hereditary hemorrhagic
      telangiectasia. APPROACH AND RESULTS: In this work, we report that a reduction in
      ALK1 gene dosage (heterozygous ALK1+/- mice) results in enhanced retinal
      endothelial cell proliferation and vascular hyperplasia at the sprouting front.
      We found that BMP9/ALK1 represses VEGF (vascular endothelial growth factor)
      mediated PI3K (phosphatidylinositol 3-kinase) by promoting the activity of the
      PTEN (phosphatase and tensin homolog). Consequently, loss of ALK1 function in
      endothelial cells results in increased activity of the PI3K pathway. These
      results were confirmed in cutaneous telangiectasia biopsies of patients with
      hereditary hemorrhagic telangiectasia 2, in which we also detected an increase in
      endothelial cell proliferation linked to an increase on the PI3K pathway. In
      mice, genetic and pharmacological inhibition of PI3K is sufficient to abolish the
      vascular hyperplasia of ALK1+/- retinas and in turn normalize the vasculature.
      CONCLUSIONS: Overall, our results indicate that the BMP9/ALK1 hub critically
      mediates vascular quiescence by limiting PI3K signaling and suggest that PI3K
      inhibitors could be used as novel therapeutic agents to treat hereditary
      hemorrhagic telangiectasia.

PMID- 29449338
TI  - Status of Hypertension in China: Results From the China Hypertension Survey, 2012
      2015.
AB  - BACKGROUND: Although the prevalence of hypertension (HTN) continues to increase
      in developing countries, including China, recent data are lacking. A nationwide
      survey was conducted from October 2012 to December 2015 to assess the prevalence
      of HTN in China. METHODS: A stratified multistage random sampling method was used
      to obtain a nationally representative sample of 451 755 residents >=18 years of
      age from 31 provinces in mainland China from October 2012 to December 2015. Blood
      pressure (BP) was measured after resting for 5 minutes by trained staff using a
      validated oscillometric BP monitor. HTN was defined as systolic BP (SBP) >=140 mm
      Hg/or diastolic BP (DBP) >=90 mm Hg or use of antihypertensive medication within
      2 weeks. Pre-HTN was defined as SBP 120 to 139 mm Hg and DBP 80 to 89 mm Hg
      without antihypertensive medication. HTN control was defined as SBP <140 mm Hg
      and DBP<90 mm Hg. In addition, the prevalence of HTN (SBP >=130 or DBP >=80 mm
      Hg) and control rate (SBP <130 and DBP <80 mm Hg) of HTN were also estimated
      according to the 2017 American College of Cardiology/American Heart Association
      High Blood Pressure Guideline. RESULTS: Overall, 23.2% (~244.5 million) of the
      Chinese adult population >=18 years of age had HTN, and another 41.3% (~435.3
      million) had pre-HTN according to the Chinese guideline. There were no
      significant differences of HTN prevalence between urban and rural residents
      (23.4% versus 23.1%, P=0.819). Among individuals with HTN, 46.9% were aware of
      their condition, 40.7% were taking prescribed antihypertensive medications, and
      15.3% had controlled HTN. Calcium channel blockers were the most commonly used
      antihypertensive medication (46.5%) as monotherapy, and 31.7% of treated
      hypertensive patients used >=2 medications. The prevalence of HTN based on the
      2017 American College of Cardiology/American Heart Association guideline was
      twice as high as that based on 2010 Chinese guideline (46.4%), whereas the
      control rate fell to 3.0%. CONCLUSIONS: In China, there is a high prevalence of
      HTN and pre-HTN, and awareness, treatment, and control of HTN were low.
      Management of medical therapy for HTN needs to improve.

PMID- 29449341
TI  - Airway Autoimmune Inflammatory Response (AAIR) Syndrome: An Asthma-Autoimmune
      Overlap Disorder?
AB  - Asthma encompasses numerous phenotypes that may require alternate approaches to
      diagnosis and therapy, particularly for patients whose symptoms remain poorly
      controlled despite escalating treatment. We describe 3 patients with apparent
      asthma who demonstrated unusual findings on cryobiopsy by flexible bronchoscopy
      and responded to therapy directed against autoimmune disease.

PMID- 29449342
TI  - Epilepsy in Children After Pandemic Influenza Vaccination.
AB  - OBJECTIVES: To determine if pandemic influenza vaccination was associated with an
      increased risk of epilepsy in children. METHODS: Information from Norwegian
      registries from 2006 through 2014 on all children <18 years living in Norway on
      October 1, 2009 was used in Cox regression models to estimate hazard ratios for
      incident epilepsy after vaccination. A self-controlled case series analysis was
      used to estimate incidence rate ratios in defined risk periods after pandemic
      vaccination. RESULTS: In Norway, the main period of the influenza A subtype H1N1
      pandemic was from October 2009 to December 2009. On October 1, 2009, 1 154 113
      children <18 years of age were registered as residents in Norway. Of these, 572
      875 (50.7%) were vaccinated against pandemic influenza. From October 2009 through
      2014 there were 3628 new cases of epilepsy (incidence rate 6.09 per 10 000 person
      years). The risk of epilepsy was not increased after vaccination: hazard ratio:
      1.07; 95% confidence interval: 0.94-1.23. Results from the self-controlled case
      series analysis supported the finding of no association between vaccination and
      subsequent epilepsy. CONCLUSIONS: Pandemic influenza vaccination was not
      associated with increased risk of epilepsy. Concerns about pandemic vaccination
      causing epilepsy in children seem to be unwarranted.

PMID- 29449343
TI  - Extrahepatic angiogenesis hinders recovery of portal hypertension and collaterals
      in rats with cirrhosis resolution.
AB  - Liver cirrhosis is characterized by portal hypertension. However, the alteration
      of portal hypertension-related derangements during cirrhosis resolution is not
      well known. The present study aimed to establish animal models with cirrhosis
      resolution and to investigate the relevant changes during this process. Male
      Sprague-Dawley rats were applied. In reverse thioacetamide (rTAA) model, rats
      were randomly allocated into four groups with control, thioacetamide (TAA)
      cirrhosis and rTAA groups that discontinued TAA for 4 or 8 weeks after cirrhosis
      induction. In reverse bile duct ligation (rBDL) model, rats received
      choledochoduodenal shunt surgery upon the establishment of cirrhosis and 4, 8, or
      16 weeks were allowed after the surgery. At the end, portal hypertension-related
      parameters were evaluated. Cirrhosis resolution was observed in rTAA groups.
      Portal pressure (PP) decreased after cirrhosis resolution but remained higher
      than control group (control, TAA, rTAA4, rTAA8 (mmHg): 5.4 +/- 0.3, 12.9 +/- 0.3,
      8.6 +/- 0.4, 7.6 +/- 0.6). Further survey found the increased splanchnic blood
      flow did not reduce during cirrhosis resolution. The extrahepatic pathological
      angiogenesis was not ameliorated (% of mesenteric window area: 1.2 +/- 0.3, 7.3
      +/- 1.1, 8.3 +/- 1.0, 11.3 +/- 2.7). In collateral system, the shunting degree
      reduced while the vessels structure remained. The vascular contractility of all
      systems and nitric oxide (NO) production were normalized. In rBDL series, PP
      decreased in rBDL16 groups but the extrahepatic angiogenesis persisted. In
      conclusion, cirrhosis resolution attenuates but not completely normalizes portal
      hypertension because of persistently high splanchnic inflow and angiogenesis. In
      clinical setting, vascular complications such as varices could persist after
      cirrhosis resolution and further investigation to define the follow-up and
      treatment strategies is anticipated.

PMID- 29449344
TI  - Defeating Major Contaminants in Fe3+- Immobilized Metal Ion Affinity
      Chromatography (IMAC) Phosphopeptide Enrichment.
AB  - Here we demonstrate that biomolecular contaminants, such as nucleic acid
      molecules, can seriously interfere with immobilized metal ion affinity
      chromatography (IMAC)-based phosphopeptide enrichments. We address and largely
      solve this issue, developing a robust protocol implementing methanol/chloroform
      protein precipitation and enzymatic digestion using benzonase, which degrades all
      forms of DNA and RNA, before IMAC-column loading. This simple procedure resulted
      in a drastic increase of enrichment sensitivity, enabling the identification of
      around 17,000 unique phosphopeptides and 12,500 unambiguously localized
      phosphosites in human cell-lines from a single LC-MS/MS run, constituting a 50%
      increase when compared with the standard protocol. The improved protocol was also
      applied to bacterial samples, increasing the number of identified bacterial
      phosphopeptides even more strikingly, by a factor 10, when compared with the
      standard protocol. For E. coli we detected around 1300 unambiguously localized
      phosphosites per LC-MS/MS run. The preparation of these ultra-pure phosphopeptide
      samples only requires marginal extra costs and sample preparation time and should
      thus be adoptable by every laboratory active in the field of phosphoproteomics.

PMID- 29449345
TI  - Antimicrobial activity of a novel bioengineered honey against non-typeable
      Haemophilus influenzae biofilms: an in vitro study.
AB  - The opportunistic pathogen non-typeable Haemophilus influenzae (NTHi) plays an
      important role in many chronic respiratory diseases including otitis media,
      chronic rhinosinusitis, cystic fibrosis and chronic obstructive pulmonary
      disease. Biofilm formation has been implicated in NTHi colonisation, persistence
      of infection and recalcitrance towards antimicrobials. There is therefore a
      pressing need for the development of novel treatment strategies that are
      effective against NTHi biofilm-associated diseases. SurgihoneyRO is a honey-based
      product that has been bioengineered to enable the slow release of H2O2, a
      reactive oxygen species to which H. influenzae is susceptible. Treatment of
      established NTHi biofilms with SurgihoneyRO significantly reduced biofilm
      viability through enhanced H2O2 production and was shown to be more effective
      than the conventional antibiotic co-amoxiclav.

PMID- 29449346
TI  - Shikonin suppresses proliferation and induces apoptosis in endometrioid
      endometrial cancer cells via modulating miR-106b/PTEN/AKT/mTOR signaling pathway.
AB  - Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal
      herb, which exerts anticancer effects in various cancers. However, the molecular
      mechanisms underlying the therapeutic effects of shikonin against endometrioid
      endometrial cancer (EEC) have not yet been fully elucidated. Herein, we
      investigated anticancer effects of shikonin on EEC cells and explored the
      underlying molecular mechanism. We observed that shikonin inhibits proliferation
      in human EEC cell lines in a dose-dependent manner. Moreover, shikonin-induced
      apoptosis was characterized by the up-regulation of the pro-apoptotic proteins
      cleaved-Caspase-3 and Bax, and the down-regulation of the anti-apoptotic protein
      Bcl-2. Microarray analyses demonstrated that shikonin induces many miRNAs'
      dysregulation, and miR-106b was one of the miRNAs being most significantly down
      regulated. miR-106b was identified to exert procancer effect in various cancers,
      but in EEC remains unclear. We first confirmed that miR-106b is up-regulated in
      EEC tissues and cells, and knockdown of miR-106b suppresses proliferation and
      promotes apoptosis. Meanwhile, our results validated that the restored expression
      of miR-106b abrogates the antiproliferative and pro-apoptotic effects of
      shikonin. We also identified that miR-106b targets phosphatase and tensin homolog
      (PTEN), a tumor suppressor gene, which in turn modulates AKT/mTOR signaling
      pathway. Our findings indicated that shikonin inhibits proliferation and promotes
      apoptosis in human EEC cells by modulating the miR-106b/PTEN/AKT/mTOR signaling
      pathway, suggesting shikonin could act a potential therapeutic agent in the EEC
      treatment.

PMID- 29449347
TI  - Association of tumor necrosis factor-alpha (TNF-alpha) gene promoter
      polymorphisms with aggressive and chronic periodontitis in the eastern Indian
      population.
AB  - Background: Periodontitis is a very common inflammatory oral disease. Tumor
      necrosis factor-alpha (TNF-alpha) is a cytokine that has been involved with the
      gingival tissue destruction and remodeling occurrence. We investigated the
      association of single nucleotide polymorphisms (SNPs) in TNF-alpha gene promoter
      region with the susceptibility of aggressive and chronic periodontitis in the
      eastern Indian population.Methods: A total of 397 DNA samples from venous blood
      were isolated. 40 individuals were aggressive periodontitis patients, 157 were
      identified chronic periodontitis patients, and the remaining 200 were healthy
      individuals. Five SNPs of TNF-alpha at promoter region (rs361525, rs1800629,
      rs1799724, rs1800630, and rs1799964) were genotyped by PCR-sequencing in
      periodontitis patients and control subjects.Results: rs1800629 (-308G/A)
      polymorphism was more frequent in both aggressive and chronic periodontitis
      patients compared with the control population, though the allele frequency was
      different only in aggressive periodontitis patients. On the other hand, both the
      genotypic and allelic variation of rs361525 (-238G/A) polymorphism were found
      significantly less frequently in aggressive and chronic periodontitis than in
      controls. The other polymorphisms like rs1799724 (-857C/T) and rs1799964 (
      1031T/C) were significantly different between chronic periodontitis patients and
      control subjects.Conclusion: The findings suggest that the rs1800629 (-308G/A)
      polymorphism of TNF-alpha gene is associated with both aggressive and chronic
      periodontitis while rs1799724 (-857C/T) and rs1799964 (-1031T/C) polymorphisms of
      TNF-alpha gene is associated only with the increased susceptibility to chronic
      periodontitis.

PMID- 29449348
TI  - Mitotic waves in the early embryogenesis of Drosophila: Bistability traded for
      speed.
AB  - Early embryogenesis of most metazoans is characterized by rapid and synchronous
      cleavage divisions. Chemical waves of Cdk1 activity were previously shown to
      spread across Drosophila embryos, and the underlying molecular processes were
      dissected. Here, we present the theory of the physical mechanisms that control
      Cdk1 waves in Drosophila The in vivo dynamics of Cdk1 are captured by a
      transiently bistable reaction-diffusion model, where time-dependent reaction
      terms account for the growing level of cyclins and Cdk1 activation across the
      cell cycle. We identify two distinct regimes. The first one is observed in
      mutants of the mitotic switch. There, waves are triggered by the classical
      mechanism of a stable state invading a metastable one. Conversely, waves in wild
      type reflect a transient phase that preserves the Cdk1 spatial gradients while
      the overall level of Cdk1 activity is swept upward by the time-dependent reaction
      terms. This unique mechanism generates a wave-like spreading that differs from
      bistable waves for its dependence on dynamic parameters and its faster speed.
      Namely, the speed of "sweep" waves strikingly decreases as the strength of the
      reaction terms increases and scales as the powers 3/4, -1/2, and 7/12 of Cdk1
      molecular diffusivity, noise amplitude, and rate of increase of Cdk1 activity in
      the cell-cycle S phase, respectively. Theoretical predictions are supported by
      numerical simulations and experiments that couple quantitative measurements of
      Cdk1 activity and genetic perturbations of the accumulation rate of cyclins.
      Finally, our analysis bears upon the inhibition required to suppress Cdk1 waves
      at the cell-cycle pause for the maternal-to-zygotic transition.

PMID- 29449349
TI  - Reply to Goldfarb et al.: On the heritability and socialization of trust and
      distrust.

PMID- 29449350
TI  - Heritability of trust and distrust remains unknown.

PMID- 29449351
TI  - Regional variation and predictors of over-registration in English primary care in
      2014: a spatial analysis.
AB  - BACKGROUND: There are more people registered with a general practice in England
      than are estimated to be resident in the country. The reasons behind this are not
      fully understood. We investigated the levels of over-registration (or under
      registration) in English primary care, their regional variability and their
      association with population and geographical characteristics. METHODS: This was a
      cross-sectional study using mid-year population estimates for 2014 and general
      practice populations for the same year. We calculated levels of patient
      registration with English primary care, in relation to census-derived population
      estimates, at various geographical levels of interest: regions, clinical
      commissioning groups and lower super output areas (LSOAs, 2011 census derived
      geographical areas of 1500 people on average). We used linear regressions to
      investigate the relationship between levels of registration and area deprivation,
      urbanicity, ethnicity, age, sex and mean distance to practice. RESULTS: The total
      over-registration rate for England was 3.9% (2 097 101 people) but there was wide
      regional variability. London had significantly higher levels of over-registration
      (6.0% and 515 063 people) than other areas in England. Higher levels of over
      registration at the LSOA level were associated with greater proportions of non
      White British residents, women, elderly people and higher levels of social
      deprivation. CONCLUSION: Our findings indicate that high mobility and health need
      may be the underlying causes of over-registrations. The regional variation in
      over-registration, with London being an outlier, points towards potential
      inequalities in resourcing of primary care and the ability of the National Health
      Service to adequately match funding to population need.

PMID- 29449352
TI  - Association between short sleep duration and carotid atherosclerosis modified by
      age in a Chinese community population.
AB  - BACKGROUND AND AIM: Short sleep duration is a risk factor of cardiovascular
      disorder; however, the association between short sleep duration and carotid
      atherosclerosis has not been completely characterised. The aim of this study is
      to investigate the association between short sleep duration and carotid
      atherosclerosis. METHODS: We used the cross-sectional data collected between May
      2014 and July 2014, which were based on a cardiovascular disease cohort study
      including 3798 participants aged 40 years and older who are residents of Beijing,
      China. We used logistic regression models to examine the associations between
      sleep duration and carotid atherosclerosis. RESULTS: After the adjustment of
      covariates, short sleep duration (less than 5 hours per night) was found to be
      associated with carotid atherosclerosis, and it also elevated the risk of, in
      both terms, the increment of prevalence (OR=1.31, P<0.05) and the quantity of
      carotid plaques (OR=1.28, P<0.05). When age was also taken into consideration,
      the largest association, in both terms of prevalence (OR=3.46, P<0.01) and the
      number of carotid plaques (OR=4.23, P<0.01), was found in subjects over the age
      of 60 with short sleep duration. CONCLUSION: In conclusion, sleep duration less
      than 5 hours per night is associated with a higher risk of carotid
      atherosclerosis compared with subjects who sleeps for 5 or over 5 hours per
      night, and the association may be modified by age.

PMID- 29449353
TI  - Ten-Year Clinical Outcome After Circumferential Pulmonary Vein Isolation
      Utilizing the Hamburg Approach in Patients With Symptomatic Drug-Refractory
      Paroxysmal Atrial Fibrillation.
AB  - BACKGROUND: Circumferential pulmonary vein isolation (CPVI) is increasingly
      performed for the treatment of symptomatic drug-refractory paroxysmal atrial
      fibrillation. Long-term data for >10 years after CPVI are sparse. We investigated
      the long-term clinical outcome and progression of paroxysmal atrial fibrillation
      after double-lasso and 3-dimensional electroanatomical mapping-guided CPVI.
      METHODS AND RESULTS: From 2003 to 2004, 161 patients (mean age: 60+/-10 years)
      with symptomatic drug-refractory paroxysmal atrial fibrillation were
      prospectively enrolled and underwent electroanatomical mapping-guided CPVI. Right
      sided and left-sided continuous circular lesions encircling the ipsilateral
      pulmonary veins were placed with irrigated radiofrequency energy. The procedural
      end point was the absence of pulmonary vein spikes 30 minutes after CPVI verified
      by 2 spiral catheters placed within the ipsilateral pulmonary veins (double-lasso
      technique). Major periprocedural complications occurred in 5 of 161 patients
      (3.1%). Follow-up was based on outpatient clinic visits, including Holter-ECGs
      and telephonic interviews. After a single procedure and median follow-up of 129.0
      months (interquartile range, 124.7-133.1 months), stable sinus rhythm was present
      in 53 of 161 (32.9%) patients. Multiprocedural outcome after a mean of 1.73+/-0.9
      procedures and a median follow-up of 123.4 months (interquartile range, 61.0
      131.0 months) resulted in stable sinus rhythm in 101 of 161 patients (62.7%).
      Progression toward persistent atrial fibrillation was observed in 10 of 161
      patients (6.2%). CONCLUSION: Ten-year single-procedural outcome of CPVI in
      patients with paroxysmal atrial fibrillation resulted in stable sinus rhythm in
      32.9% and in 62.7% of patients after multiple procedures. The progression rate to
      persistent AF was remarkably low.

PMID- 29449354
TI  - High-Resolution Infrared Thermography of Esophageal Temperature During
      Radiofrequency Ablation of Atrial Fibrillation.
AB  - BACKGROUND: Catheter ablation for atrial fibrillation has potential to cause
      esophageal thermal injury. Esophageal temperature monitoring during ablation is
      commonly used; however, it has not eliminated thermal injuries, possibly because
      conventional sensors have poor spatial sampling and response characteristics. To
      enhance understanding of temperature dynamics that may underlie esophageal
      injury, we tested a high-resolution, intrabody, infrared thermography catheter to
      continuously image esophageal temperatures during ablation. METHODS AND RESULTS:
      Atrial fibrillation ablation patients were instrumented with a flexible, 9F
      infrared temperature catheter inserted nasally (n=8) or orally (n=8) into the
      esophagus adjacent to the left atrium. Ablation was performed while the infrared
      catheter continuously recorded surface temperatures from 7680 points per second
      circumferentially over a 6-cm length of esophagus. Physicians were blinded to
      temperature data. Endoscopy was performed within 24 hours to document esophageal
      injury. Thermal imaging showed that most patients (10/16) experienced >=1 events
      where peak esophageal temperature was >40 degrees C. Three patients experienced
      temperatures >50 degrees C; and 1 experienced >60 degrees C. Analysis of
      temperature data for each subject's maximum thermal event revealed high gradients
      (2.3+/-1.4 degrees C/mm) and rates of change (1.5+/-1.3 degrees C/s) with an
      average length of esophageal involvement of 11.0+/-5.4 mm. Endoscopy identified 3
      distinct thermal lesions, all in patients with temperatures >50 degrees C; all
      resolved within 2 weeks. CONCLUSIONS: Infrared thermography provided dynamic,
      high-resolution mapping of esophageal temperatures during cardiac ablation.
      Esophageal thermal injury occurred with temperatures >50 degrees C and was
      associated with large spatiotemporal gradients. Additional studies are warranted
      to determine the relationships between thermal parameters and esophageal injury.

PMID- 29449356
TI  - Meet the First Authors.

PMID- 29449355
TI  - Red Alert: Infrared Thermography for Esophageal Monitoring.

PMID- 29449357
TI  - Urinary Prostaglandin Metabolites: An Incomplete Reckoning and a Flush to
      Judgment.

PMID- 29449358
TI  - The Cellular Origin of Activated Fibroblasts in the Infarcted and Remodeling
      Myocardium.

PMID- 29449359
TI  - Pannexin Channel Inhibition: An Evolving Target to Lower Blood Pressure?

PMID- 29449360
TI  - Telomere Length Dynamics and Atherosclerotic Disease.

PMID- 29449361
TI  - David Gutterman: Focusing on the Little Things Leads to Big Discoveries.

PMID- 29449362
TI  - Recognizing the Top Reviewers of 2017 for Circulation Research.

PMID- 29449363
TI  - Approaching Regulatory Approval of Cardiovascular Regenerative Therapy.

PMID- 29449365
TI  - 'Big bang' of B-cell development revealed.
AB  - Earlier studies have identified transcription factors that specify B-cell fate,
      but the underlying mechanisms remain to be revealed. Two new studies by Miyai and
      colleagues (pp. 112-126) and Li and colleagues (pp. 96-111) in this issue of
      Genes & Development provide new and unprecedented insights into the genetic and
      epigenetic mechanisms that establish B-cell identity.

PMID- 29449366
TI  - Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in
      Cardiac Amyloid Disease Associated With Wild-Type Transthyretin.
AB  - BACKGROUND: Wild-type transthyretin amyloidosis (ATTRwt), an underappreciated
      cause of heart failure in older adults, is challenging to diagnose and monitor in
      the absence of validated, disease-specific biomarkers. We examined the prognostic
      use and survival association of serum TTR (transthyretin) concentration in
      ATTRwt. METHODS AND RESULTS: Patients with biopsy-proven ATTRwt were
      retrospectively identified. Serum TTR, cardiac biomarkers, and echocardiographic
      parameters were assessed at baseline and follow-up evaluations. Statistical
      analyses included Kaplan-Meier method, Cox proportional hazard survival models,
      and receiver-operating characteristic curve analysis. Median serum TTR
      concentration at presentation was 23 mg/dL (n=116). Multivariate predictors of
      shorter overall survival were decreased TTR, left ventricular ejection fraction
      and elevated cTn-I (cardiac troponin I); an inclusive model demonstrated superior
      accuracy in 4-year survival prediction by receiver-operating characteristic curve
      analysis (area under the curve, 0.77). TTR values lower than the normal limit,
      <18 mg/dL, were associated with shorter survival (2.8 versus 4.1 years; P=0.03).
      Further, TTR values at 1- and 2-year follow-ups were significantly lower
      (P<0.001) in untreated patients (n=23) compared with those treated with TTR
      stabilizer, diflunisal (n=12), after baseline evaluation. During 2-year follow
      up, unchanged TTR corresponded to increased cTn-I (P=0.006) in untreated
      patients; conversely, the diflunisal-treated group showed increased TTR (P=0.001)
      and stabilized cTn-I and left ventricular ejection fraction at 1 year.
      CONCLUSIONS: In this series of biopsy-proven ATTRwt, lower baseline serum TTR
      concentration was associated with shorter survival as an independent predictor of
      outcome. Longitudinal analysis demonstrated that decreasing TTR corresponded to
      worsening cardiac function. These data suggest that TTR may be a useful
      prognostic marker and predictor of outcome in ATTRwt.

PMID- 29449364
TI  - Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical
      Entity.
AB  - Heart failure and related morbidity and mortality are increasing at an alarming
      rate, in large part, because of increases in aging, obesity, and diabetes
      mellitus. The clinical outcomes associated with heart failure are considerably
      worse for patients with diabetes mellitus than for those without diabetes
      mellitus. In people with diabetes mellitus, the presence of myocardial
      dysfunction in the absence of overt clinical coronary artery disease, valvular
      disease, and other conventional cardiovascular risk factors, such as hypertension
      and dyslipidemia, has led to the descriptive terminology, diabetic
      cardiomyopathy. The prevalence of diabetic cardiomyopathy is increasing in
      parallel with the increase in diabetes mellitus. Diabetic cardiomyopathy is
      initially characterized by myocardial fibrosis, dysfunctional remodeling, and
      associated diastolic dysfunction, later by systolic dysfunction, and eventually
      by clinical heart failure. Impaired cardiac insulin metabolic signaling,
      mitochondrial dysfunction, increases in oxidative stress, reduced nitric oxide
      bioavailability, elevations in advanced glycation end products and collagen-based
      cardiomyocyte and extracellular matrix stiffness, impaired mitochondrial and
      cardiomyocyte calcium handling, inflammation, renin-angiotensin-aldosterone
      system activation, cardiac autonomic neuropathy, endoplasmic reticulum stress,
      microvascular dysfunction, and a myriad of cardiac metabolic abnormalities have
      all been implicated in the development and progression of diabetic
      cardiomyopathy. Molecular mechanisms linked to the underlying pathophysiological
      changes include abnormalities in AMP-activated protein kinase, peroxisome
      proliferator-activated receptors, O-linked N-acetylglucosamine, protein kinase C,
      microRNA, and exosome pathways. The aim of this review is to provide a
      contemporary view of these instigators of diabetic cardiomyopathy, as well as
      mechanistically based strategies for the prevention and treatment of diabetic
      cardiomyopathy.

PMID- 29449367
TI  - Load-Independent Systolic and Diastolic Right Ventricular Function in Heart
      Failure With Preserved Ejection Fraction as Assessed by Resting and Handgrip
      Exercise Pressure-Volume Loops.
AB  - BACKGROUND: Although systolic right ventricular (RV) dysfunction has been shown
      to be a potent predictor for adverse outcomes in patients with heart failure with
      preserved ejection fraction (HFpEF), RV functional abnormalities in the course of
      the syndrome are not well characterized. We, therefore, sought to assess load
      independent and load-dependent systolic and diastolic characteristics of RV
      function in stable outpatients with HFpEF. METHODS AND RESULTS: We invasively
      obtained RV and left ventricular pressure-volume loops in 24 HFpEF patients and 9
      patients without heart failure symptoms with a conductance catheter during basal
      conditions and handgrip exercise. Transient preload reduction was used to
      extrapolate the RV end-systolic elastance and diastolic stiffness constant. HFpEF
      patients and controls showed similar left ventricular and RV dimensions and
      ejection fractions with elevated left ventricular filling pressures. In HFpEF
      patients, invasively determined load-independent RV contractility (P=0.04) and
      load-independent passive RV stiffness constant beta (P<0.01) were elevated.
      Although RV relaxation and cardiac output were similar at baseline, HFpEF
      patients demonstrated a blunted increase in cardiac output under exercise
      (P=0.01) associated with prolonged RV relaxation (P=0.01), decrease in stroke
      volume (P<0.01), higher RV-filling pressures (P<0.01), and a marked increase in
      the end-diastolic pressure-volume relationship (P<0.01). CONCLUSIONS: In
      compensated stages of the HFpEF syndrome, systolic RV function is preserved, but
      diastolic abnormalities with intrinsic RV stiffness and prolonged RV relaxation
      are already present. Impaired diastolic RV reserve contributes to a blunted
      increase in cardiac output during exertion. Because impairments in diastolic
      function seem to be a biventricular phenomenon, RV diastolic dysfunction warrants
      further consideration when characterizing HFpEF patients. CLINICAL TRIAL
      REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT02459626.

PMID- 29449368
TI  - Immunosuppressive Therapy Improves Both Short- and Long-Term Prognosis in
      Patients With Virus-Negative Nonfulminant Inflammatory Cardiomyopathy.
AB  - BACKGROUND: Inflammatory cardiomyopathy (infl-CMP) is characterized by increased
      cardiac inflammation in the absence of viruses, ischemia, valvular disease, or
      other apparent causes. Studies addressing the efficacy of immunosuppressive
      therapy in patients with infl-CMP are sparse. This study retrospectively
      investigates whether immunosuppressive agents on top of heart failure therapy
      according to current guidelines improves cardiac function and long-term outcome
      in patients with infl-CMP. METHODS AND RESULTS: Within the Innsbruck and
      Maastricht Cardiomyopathy Registry, a total of 209 patients fulfilled the
      criteria for infl-CMP using endomyocardial biopsy (>=14 infiltrating inflammatory
      cells/mm2). A total of 110 (53%) patients received immunosuppressive therapy and
      99 (47%) did not. To correct for potential selection bias, 1:1 propensity score
      matching was used on all significant baseline parameters, resulting in a total of
      90 patients per group. Baseline characteristics did not significantly differ
      between both patient groups, reflecting optimal propensity score matching. After
      a median follow-up of 31 (15-47) months, immunosuppressive therapy resulted in an
      improved long-term outcome (eg, heart transplantation-free survival) as compared
      with standard heart failure therapy alone (Log-rank P=0.043; hazard ratio, 0.34
      [95% CI, 0.17-0.92]) and in a significant larger increase of left ventricular
      ejection fraction after a mean of 12 months follow-up, as compared with patients
      receiving standard heart failure treatment only (12.2% versus 7.3%, respectively;
      P=0.036). CONCLUSIONS: To conclude, this study suggests that immunosuppressive
      therapy in infl-CMP patients results in an improved heart transplantation-free
      survival as compared with standard heart failure therapy alone, underscoring the
      urgent need for a large prospective multicenter trial.

PMID- 29449369
TI  - Serum Transthyretin: Predictor of Amyloidosis Outcomes?

PMID- 29449370
TI  - Structural basis for antibody targeting of the broadly expressed microbial
      polysaccharide poly-N-acetylglucosamine.
AB  - In response to the widespread emergence of antibiotic-resistant microbes, new
      therapeutic agents are required for many human pathogens. A non-mammalian
      polysaccharide, poly-N-acetyl-d-glucosamine (PNAG), is produced by bacteria,
      fungi, and protozoan parasites. Antibodies that bind to PNAG and its deacetylated
      form (dPNAG) exhibit promising in vitro and in vivo activities against many
      microbes. A human IgG1 mAb (F598) that binds both PNAG and dPNAG has opsonic and
      protective activities against multiple microbial pathogens and is undergoing
      preclinical and clinical assessments as a broad-spectrum antimicrobial therapy.
      Here, to understand how F598 targets PNAG, we determined crystal structures of
      the unliganded F598 antigen-binding fragment (Fab) and its complexes with N
      acetyl-d-glucosamine (GlcNAc) and a PNAG oligosaccharide. We found that F598
      recognizes PNAG through a large groove-shaped binding site that traverses the
      entire light- and heavy-chain interface and accommodates at least five GlcNAc
      residues. The Fab-GlcNAc complex revealed a deep binding pocket in which the
      monosaccharide and a core GlcNAc of the oligosaccharide were almost identically
      positioned, suggesting an anchored binding mechanism of PNAG by F598. The Fab
      used in our structural analyses retained binding to PNAG on the surface of an
      antibiotic-resistant, biofilm-forming strain of Staphylococcus aureus
      Additionally, a model of intact F598 binding to two pentasaccharide epitopes
      indicates that the Fab arms can span at least 40 GlcNAc residues on an extended
      PNAG chain. Our findings unravel the structural basis for F598 binding to PNAG on
      microbial surfaces and biofilms.

PMID- 29449371
TI  - Biochemical characterization and essentiality of Plasmodium fumarate hydratase.
AB  - Plasmodium falciparum (Pf), the causative agent of malaria, has an iron-sulfur
      cluster-containing class I fumarate hydratase (FH) that catalyzes the
      interconversion of fumarate to malate, a well-known reaction in the tricarboxylic
      acid cycle. In humans, the same reaction is catalyzed by class II FH that has no
      sequence or structural homology with the class I enzyme from Plasmodium Fumarate
      is generated in large quantities in the parasite as a by-product of AMP synthesis
      and is converted to malate by FH and then used in the generation of the key
      metabolites oxaloacetate, aspartate, and pyruvate. Previous studies have
      identified the FH reaction as being essential to P. falciparum, but biochemical
      characterization of PfFH that may provide leads for the development of specific
      inhibitors is lacking. Here, we report on the kinetic characterization of
      purified recombinant PfFH, functional complementation of fh deficiency in
      Escherichia coli, and mitochondrial localization in the parasite. We found that
      the substrate analog mercaptosuccinic acid is a potent PfFH inhibitor, with a Ki
      value in the nanomolar range. The fh gene could not be knocked out in Plasmodium
      berghei when transfectants were introduced into BALB/c mice; however, fh knockout
      was successful when C57BL/6 mice were used as host, suggesting that the
      essentiality of the fh gene to the parasite was mouse strain-dependent.

PMID- 29449372
TI  - Ligand-mediated protein degradation reveals functional conservation among
      sequence variants of the CUL4-type E3 ligase substrate receptor cereblon.
AB  - Upon binding to thalidomide and other immunomodulatory drugs, the E3 ligase
      substrate receptor cereblon (CRBN) promotes proteosomal destruction by engaging
      the DDB1-CUL4A-Roc1-RBX1 E3 ubiquitin ligase in human cells but not in mouse
      cells, suggesting that sequence variations in CRBN may cause its inactivation.
      Therapeutically, CRBN engagers have the potential for broad applications in
      cancer and immune therapy by specifically reducing protein expression through
      targeted ubiquitin-mediated degradation. To examine the effects of defined
      sequence changes on CRBN's activity, we performed a comprehensive study using
      complementary theoretical, biophysical, and biological assays aimed at
      understanding CRBN's nonprimate sequence variations. With a series of recombinant
      thalidomide-binding domain (TBD) proteins, we show that CRBN sequence variants
      retain their drug-binding properties to both classical immunomodulatory drugs and
      dBET1, a chemical compound and targeting ligand designed to degrade bromodomain
      containing 4 (BRD4) via a CRBN-dependent mechanism. We further show that dBET1
      stimulates CRBN's E3 ubiquitin-conjugating function and degrades BRD4 in both
      mouse and human cells. This insight paves the way for studies of CRBN-dependent
      proteasome-targeting molecules in nonprimate models and provides a new
      understanding of CRBN's substrate-recruiting function.

PMID- 29449373
TI  - Tyrosine hydroxylase down-regulation after loss of Abelson helper integration
      site 1 (AHI1) promotes depression via the circadian clock pathway in mice.
AB  - Abelson helper integration site 1 (AHI1) is associated with several
      neuropsychiatric and brain developmental disorders, such as schizophrenia,
      depression, autism, and Joubert syndrome. Ahi1 deficiency in mice leads to
      behaviors typical of depression. However, the mechanisms by which AHI1 regulates
      behavior remain to be elucidated. Here, we found that down-regulation of
      expression of the rate-limiting enzyme in dopamine biosynthesis, tyrosine
      hydroxylase (TH), in the midbrains of Ahi1-knockout (KO) mice is responsible for
      Ahi1-deficiency-mediated depressive symptoms. We also found that Rev-Erbalpha, a
      TH transcriptional repressor and circadian regulator, is up-regulated in the Ahi1
      KO mouse midbrains and Ahi1-knockdown Neuro-2a cells. Moreover, brain and muscle
      Arnt-like protein 1 (BMAL1), the Rev-Erbalpha transcriptional regulator, is also
      increased in the Ahi1-KO mouse midbrains and Ahi1-knockdown cells. Our results
      further revealed that AHI1 decreases BMAL1/Rev-Erbalpha expression by interacting
      with and repressing retinoic acid receptor-related orphan receptor alpha, a
      nuclear receptor and transcriptional regulator of circadian genes. Of note, Bmal1
      deficiency reversed the reduction in TH expression induced by Ahi1 deficiency.
      Moreover, microinfusion of the Rev-Erbalpha inhibitor SR8278 into the ventral
      midbrain of Ahi1-KO mice significantly increased TH expression in the ventral
      tegmental area and improved their depressive symptoms. These findings provide a
      mechanistic explanation for a link between AHI1-related behaviors and the
      circadian clock pathway, indicating an involvement of circadian regulatory
      proteins in AHI1-regulated mood and behavior.

PMID- 29449374
TI  - Time-resolved analysis of amino acid stress identifies eIF2 phosphorylation as
      necessary to inhibit mTORC1 activity in liver.
AB  - Amino acid availability is sensed by GCN2 (general control nonderepressible 2)
      and mechanistic target of rapamycin complex 1 (mTORC1), but how these two sensors
      coordinate their respective signal transduction events remains mysterious. In
      this study we utilized mouse genetic models to investigate the role of GCN2 in
      hepatic mTORC1 regulation upon amino acid stress induced by a single injection of
      asparaginase. We found that deletion of Gcn2 prevented hepatic phosphorylation of
      eukaryotic initiation factor 2alpha to asparaginase and instead unleashed mTORC1
      activity. This change in intracellular signaling occurred within minutes and
      resulted in increased 5'-terminal oligopyrimidine mRNA translation instead of
      activating transcription factor 4 synthesis. Asparaginase also promoted hepatic
      mRNA levels of several genes which function as mTORC1 inhibitors, and these genes
      were blunted or blocked in the absence of Gcn2, but their timing could not
      explain the early discordant effects in mTORC1 signaling. Preconditioning mice
      with a chemical endoplasmic reticulum stress agent before amino acid stress
      rescued normal mTORC1 repression in the liver of Gcn2-/- mice but not in livers
      with both Gcn2 and the endoplasmic reticulum stress kinase, Perk, deleted.
      Furthermore, treating wildtype and Gcn2-/- mice with ISRIB, an inhibitor of PERK
      signaling, also failed to alter hepatic mTORC1 responses to asparaginase,
      although administration of ISRIB alone had an inhibitory GCN2-independent effect
      on mTORC1 activity. Taken together, the data show that activating transcription
      factor 4 is not required, but eukaryotic initiation factor 2alpha phosphorylation
      is necessary to prevent mTORC1 activation during amino acid stress.

PMID- 29449375
TI  - Novosphingobium aromaticivorans uses a Nu-class glutathione S-transferase as a
      glutathione lyase in breaking the beta-aryl ether bond of lignin.
AB  - As a major component of plant cell walls, lignin is a potential renewable source
      of valuable chemicals. Several sphingomonad bacteria have been identified that
      can break the beta-aryl ether bond connecting most phenylpropanoid units of the
      lignin heteropolymer. Here, we tested three sphingomonads predicted to be capable
      of breaking the beta-aryl ether bond of the dimeric aromatic compound
      guaiacylglycerol-beta-guaiacyl ether (GGE) and found that Novosphingobium
      aromaticivorans metabolizes GGE at one of the fastest rates thus far reported.
      After the ether bond of racemic GGE is broken by replacement with a thioether
      bond involving glutathione, the glutathione moiety must be removed from the
      resulting two stereoisomers of the phenylpropanoid conjugate beta-glutathionyl
      gamma-hydroxypropiovanillone (GS-HPV). We found that the Nu-class glutathione S
      transferase NaGSTNu is the only enzyme needed to remove glutathione from both (R)
      and (S)-GS-HPV in N. aromaticivorans We solved the crystal structure of NaGSTNu
      and used molecular modeling to propose a mechanism for the glutathione lyase
      (deglutathionylation) reaction in which an enzyme-stabilized glutathione thiolate
      attacks the thioether bond of GS-HPV, and the reaction proceeds through an enzyme
      stabilized enolate intermediate. Three residues implicated in the proposed
      mechanism (Thr51, Tyr166, and Tyr224) were found to be critical for the lyase
      reaction. We also found that Nu-class GSTs from Sphingobium sp. SYK-6 (which can
      also break the beta-aryl ether bond) and Escherichia coli (which cannot break the
      beta-aryl ether bond) can also cleave (R)- and (S)-GS-HPV, suggesting that
      glutathione lyase activity may be common throughout this widespread but largely
      uncharacterized class of glutathione S-transferases.

PMID- 29449377
TI  - Haploid embryonic stem cells can be enriched and maintained by simple filtration.
AB  - Mammalian haploid embryonic stem cells (haESCs) serve as a powerful tool for
      genetic analyses at both the cellular and organismal levels. However, spontaneous
      diploidization of haESCs limits their use in these analyses. Addition of small
      molecules to the culture medium to control the cell cycle can slow down
      diploidization, but cell-sorting methods such as FACS are still required to
      enrich haploid cells for long-term maintenance in vitro Here, acting on our
      observation that haploid and diploidized cells differ in diameter, we developed a
      simplified filtration method to enrich haploid cells from cultured haESCs. We
      found that regular cell filtration with this system reliably maintained the
      haploidy of mouse haESCs for over 30 passages. Importantly, CRISPR/Cas9-mediated
      knockout and knockin were successfully achieved in the filtered cells, leading to
      stable haploid cell lines carrying the desired gene modifications. Of note, by
      injecting haESCs into metaphase II oocytes, we efficiently obtained live mice
      with the expected genetic traits, indicating that regular filtration maintained
      the functional integrity of haESCs. Moreover, this filtration system was also
      feasible for derivation of mouse haESCs from parthenogenetic haploid blastocysts
      and for human haESC maintenance. In conclusion, we have identified a reliable,
      efficient, and easy-to-handle technique for countering diploidization of haploid
      cells, a major obstacle in haESC applications.

PMID- 29449376
TI  - Structural basis for the glycosyltransferase activity of the Salmonella effector
      SseK3.
AB  - The Salmonella-secreted effector SseK3 translocates into host cells, targeting
      innate immune responses, including NF-kappaB activation. SseK3 is a
      glycosyltransferase that transfers an N-acetylglucosamine (GlcNAc) moiety onto
      the guanidino group of a target arginine, modulating host cell function. However,
      a lack of structural information has precluded elucidation of the molecular
      mechanisms in arginine and GlcNAc selection. We report here the crystal structure
      of SseK3 in its apo form and in complex with hydrolyzed UDP-GlcNAc. SseK3
      possesses the typical glycosyltransferase type-A (GT-A)-family fold and the metal
      coordinating DXD motif essential for ligand binding and enzymatic activity.
      Several conserved residues were essential for arginine GlcNAcylation and SseK3
      mediated inhibition of NF-kappaB activation. Isothermal titration calorimetry
      revealed SseK3's preference for manganese coordination. The pattern of
      interactions in the substrate-bound SseK3 structure explained the selection of
      the primary ligand. Structural rearrangement of the C-terminal residues upon
      ligand binding was crucial for SseK3's catalytic activity, and NMR analysis
      indicated that SseK3 has limited UDP-GlcNAc hydrolysis activity. The release of
      free N-acetyl alpha-d-glucosamine, and the presence of the same molecule in the
      SseK3 active site, classified it as a retaining glycosyltransferase. A glutamate
      residue in the active site suggested a double-inversion mechanism for the
      arginine N-glycosylation reaction. Homology models of SseK1, SseK2, and the
      Escherichia coli orthologue NleB1 reveal differences in the surface electrostatic
      charge distribution, possibly accounting for their diverse activities. This first
      structure of a retaining GT-A arginine N-glycosyltransferase provides an
      important step toward a better understanding of this enzyme class and their roles
      as bacterial effectors.

PMID- 29449378
TI  - Complete Genome Sequences of Six Listeria monocytogenes Sequence Type 9 Isolates
      from Meat Processing Plants in Norway.
AB  - Listeria monocytogenes is a foodborne pathogen that causes the often-fatal
      disease listeriosis. We present here the complete genome sequences of six L.
      monocytogenes isolates of sequence type 9 (ST9) collected from two different meat
      processing facilities in Norway. The genomes were assembled using Illumina and
      Nanopore sequencing data.

PMID- 29449379
TI  - Draft Genome Sequence of the Nitrogen-Fixing and Hormogonia-Inducing
      Cyanobacterium Nostoc cycadae Strain WK-1, Isolated from the Coralloid Roots of
      Cycas revoluta.
AB  - We report here the whole-genome sequence of Nostoc cycadae strain WK-1, which was
      isolated from cyanobacterial colonies growing in the coralloid roots of the
      gymnosperm Cycas revoluta It can provide valuable resources to study the
      mutualistic relationships and the syntrophic metabolisms between the
      cyanobacterial symbiont and the host plant, C. revoluta.

PMID- 29449380
TI  - Annotated Genome Sequences of 16 Lineage 4 Mycobacterium tuberculosis Strains
      from Guatemala.
AB  - Whole-genome sequencing has resulted in new insights into the phylogeography of
      Mycobacterium tuberculosis However, only limited genomic data are available from
      M. tuberculosis strains in Guatemala. Here we report 16 complete genomes of
      clinical strains belonging to the Euro-American lineage 4, the most common
      lineage found in Guatemala and Central America.

PMID- 29449381
TI  - Complete Genome Sequence of Pseudomonas sp. Strain NC02, Isolated from Soil.
AB  - We report here the complete genome sequence of Pseudomonas sp. strain NC02,
      isolated from soil in eastern Massachusetts. We assembled PacBio reads into a
      single closed contig with 132* mean coverage and then polished this contig using
      Illumina MiSeq reads, yielding a 6,890,566-bp sequence with 61.1% GC content.

PMID- 29449382
TI  - Complete Genome Sequence of Escherichia coli ML35.
AB  - We report here the complete genome sequence of Escherichia coli strain ML35. We
      assembled PacBio reads into a single closed contig with 169* mean coverage and
      then polished this contig using Illumina MiSeq reads, yielding a 4,918,774-bp
      sequence with 50.8% GC content.

PMID- 29449383
TI  - Complete Genome Sequence of Methanobrevibacter smithii Strain KB11, Isolated from
      a Korean Fecal Sample.
AB  - The archaeon Methanobrevibacter smithii is a major colonizer of the human gut.
      Methanobrevibacter smithii strain KB11 was newly isolated from a Korean fecal
      sample. Here, we present the complete genome sequence of strain KB11 and a brief
      comparison with that of M. smithii type strain ATCC 35061T.

PMID- 29449384
TI  - Complete Genome Sequences of Five Foot-and-Mouth Disease Viruses of Serotype A
      Isolated from Cattle in Nigeria between 2013 and 2015.
AB  - The complete genome sequences of 5 foot-and-mouth disease viruses of serotype A
      are reported here. These viruses originate from outbreaks in northern Nigeria in
      2013 to 2015 and belong to the A/AFRICA/G-IV lineage.

PMID- 29449385
TI  - Complete Genome Sequences of Enterobacter cancerogenus CR-Eb1 and Enterococcus
      sp. Strain CR-Ec1, Isolated from the Larval Gut of the Greater Wax Moth, Galleria
      mellonella.
AB  - Enterobacter cancerogenus CR-Eb1 and Enterococcus sp. CR-Ec1 were isolated from
      the larval gut of Galleria mellonella, the greater wax moth. Here, we report the
      completed and annotated genome sequences of insect gut-dwelling bacteria.

PMID- 29449386
TI  - Draft Genome Sequence of Lactobacillus rhamnosus NRRL B-442, a Potential
      Probiotic Strain.
AB  - Lactic acid bacteria are known to exhibit probiotic properties through various
      mechanisms, including competitive exclusion, pathogen inhibition, production of
      antimicrobial substances, and maintenance of eubiosis. Here, we present the draft
      genome sequence of a novel probiotic strain, Lactobacillus rhamnosus strain NRRL
      B-442, which exhibits potent antivirulence activity against Salmonella enterica.

PMID- 29449387
TI  - Draft Genome Sequences of Escherichia coli Isolates from India.
AB  - Escherichia coli causes diarrhea and extraintestinal infections in humans and
      animals. Here, we report the draft genome sequences of Escherichia coli strains
      360/16 and 646, isolated from neonatal calves.

PMID- 29449388
TI  - Complete Genome Sequences of Two Vesicular Stomatitis New Jersey Viruses
      Representing the 2012 U.S. Epidemic Strain and Its Closest Relative Endemic
      Strain from Southern Mexico.
AB  - We report here the complete genome sequences of two vesicular stomatitis New
      Jersey virus (VSNJV) field strains isolated from epithelial lesions from
      naturally infected animals in Mexico and the United States. The close
      phylogenetic relationship of these isolates makes them an ideal model for
      assessing potential genetic factors linked with the emergence of VSNJV in the
      United States.

PMID- 29449389
TI  - Draft Reference Genome Sequence of Corynebacterium mastitidis 16-1433, Isolated
      from a Mouse.
AB  - We report here a nearly complete draft genome sequence for a Corynebacterium
      mastitidis isolate from a mouse. The total read coverage is 198*, and the genome
      size is 2,264,319 bp with a 69.04% GC content. This genome complements the only
      other genome available for C. mastitidis, which was obtained from a sheep.

PMID- 29449390
TI  - Analysis of the Complete Genome Sequence of Cucumber mosaic virus Strain K.
AB  - The complete genome sequence of Cucumber mosaic virus strain K was determined by
      deep RNA sequencing. The tripartite genome consists of a 3,382-nucleotide (nt)
      RNA1, a 3,050-nt RNA2, and a 2,218-nt RNA3 segment. Phylogenetic analysis placed
      RNA1 and RNA2 in subgroup IB. However, RNA3 grouped with subgroup IA isolates,
      indicating a likely recombination event.

PMID- 29449391
TI  - Complete Genome Sequence of the First Isolate of Hibiscus Latent Singapore Virus
      Detected in Japan.
AB  - The complete genome sequence of the first Japanese isolate of hibiscus latent
      Singapore virus (HLSV-J) was determined. The genomes of HLSV-J and a reported
      isolate from Singapore had only 86.7% nucleotide identity, while the encoded
      proteins shared amino acid identities of more than 95%.

PMID- 29449392
TI  - Closed Genome Sequence of Phytopathogen Biocontrol Agent Bacillus velezensis
      Strain AGVL-005, Isolated from Soybean.
AB  - We report here the closed and near-complete genome sequence and annotation of
      Bacillus velezensis strain AGVL-005, a bacterium isolated from soybean seeds in
      Brazil and used for phytopathogen biocontrol.

PMID- 29449393
TI  - Full-Length Genome Sequences of Two Chinese Porcine Circovirus Type 3 Strains,
      NWHEB21 and NWHUN2.
AB  - Two porcine circovirus 3 (PCV3) strains, named NWHEB21 and NWHUN2, were
      identified in heart and brain tissues of aborted piglets. Their complete genome
      sequences were sequenced and analyzed to further characterize PCV3 in China and
      worldwide.

PMID- 29449394
TI  - Draft Genome Sequence of Lactobacillus paracasei DUP 13076, Which Exhibits Potent
      Antipathogenic Effects against Salmonella enterica Serovars Enteritidis,
      Typhimurium, and Heidelberg.
AB  - Lactobacillus paracasei DUP 13076 demonstrates antagonistic effects against the
      foodborne pathogens Salmonella enterica serovars Enteritidis, Typhimurium, and
      Heidelberg in coculture and in vitro experiments. Here, we report the draft
      genome sequence of Lactobacillus paracasei DUP 13076, which has a circular
      chromosome of 3,048,314 bp and a G+C content of 46.3%.

PMID- 29449395
TI  - Complete Genome Sequence of the Bacillus pumilus Phage Leo2.
AB  - Bacillus spp. are ubiquitous Gram-positive microbes with many ecological and
      symbiotic interactions and can be pathogens. Phage Leo2 was found to infect a
      Bacillus pumilus strain isolated from soil. The sequence of phage Leo2 revealed
      74 genes; 31% of the genes have associated functions, and 67% of coding regions
      are unidentified open reading frames.

PMID- 29449396
TI  - Draft Genome Sequence of a Pathogenic Vibrio vulnificus Strain Isolated in
      Brazil.
AB  - We describe the draft genome sequence of the clinical Vibrio vulnificus strain
      03_7315, isolated in 2016 from the blood of a diabetic patient who died of
      septicemia after ingestion of seafood. The draft genome, with 4,755,588 bp
      covering two chromosomes, presented 4,434 genes, 4,213 coding sequences, and 117
      pseudogenes.

PMID- 29449397
TI  - Draft Genome Sequence of Listeria monocytogenes Strain CIIMS-PH-1, a Serovar 4b
      Isolate from Infant Septicemia.
AB  - We report here the draft genome sequence of Listeria monocytogenes CIIMS-PH-1, an
      isolate obtained from a 16-day-old infant with septicemia. The draft genome of
      CIIMS-PH-1 consisted of 2,939,183 bp and is a member of sequence type 308, clonal
      complex 1, and lineage I.

PMID- 29449398
TI  - Complete Genome Sequence of the Model Oleaginous Alga Nannochloropsis gaditana
      CCMP1894.
AB  - The model oleaginous alga Nannochloropsis gaditana was completely sequenced using
      a combination of optical mapping and next-generation sequencing technologies to
      generate one of the most complete eukaryotic genomes published to date. The
      assembled genome is 30.7 Mb long.

PMID- 29449399
TI  - Genome Sequences of 12 Pseudomonas lundensis Strains Isolated from the Lungs of
      Humans.
AB  - We report here the first complete genome sequence of a human Pseudomonas
      lundensis isolate, strain AU1044, and the draft genomes of 11 other clinical P.
      lundensis strains, isolated from the lungs of cystic fibrosis patients. The
      genome of strain AU1044 is 4.81 Mb and encodes seven 16S rRNAs.

PMID- 29449400
TI  - Complete Genome Sequence of Rice hoja blanca tenuivirus Isolated from a
      Susceptible Rice Cultivar in Colombia.
AB  - We describe here the complete genome of Rice hoja blanca tenuivirus The sequenced
      isolate was obtained by insect vector transmission from a symptomatic rice sample
      grown in Colombia. Sequence data from the four RNA components were obtained by
      deep sequencing (Illumina), and infections were confirmed by enzyme-linked
      immunosorbent assay and Sanger sequencing.

PMID- 29449401
TI  - Draft Genome Sequence of the Sordariomycete Lecythophora (Coniochaeta) hoffmannii
      CBS 245.38.
AB  - Lecythophora (Coniochaeta) hoffmannii, a soil- and lignocellulose-inhabiting
      sordariomycete (Ascomycota) that can also live as a facultative tree pathogen
      causing soft rot, belongs to the family Coniochaetaceae. The strain CBS 245.38
      sequenced here was assembled into 869 contigs, has a size of 30.8 Mb, and
      comprises 10,596 predicted protein-coding genes.

PMID- 29449402
TI  - High-Quality Draft Genome Sequences of Five Xanthomonas arboricola pv. fragariae
      Isolates.
AB  - Xanthomonas arboricola pv. fragariae was described in 2001 as the causal agent of
      strawberry bacterial leaf blight. We report here the first draft whole-genome
      sequences of five X. arboricola pv. fragariae isolates from Italy and France.

PMID- 29449403
TI  - High-Quality Complete Genome Sequences of Three Bovine Shiga Toxin-Producing
      Escherichia coli O177:H- (fliCH25) Isolates Harboring Virulent stx2 and Multiple
      Plasmids.
AB  - Shiga toxin-producing Escherichia coli (STEC) bacteria are zoonotic pathogens. We
      report here the high-quality complete genome sequences of three STEC O177:H-
      (fliCH25) strains, SMN152SH1, SMN013SH2, and SMN197SH3. The assembled genomes
      consisted of one optical map-verified circular chromosome for each strain, plus
      two plasmids for SMN013SH2 and three plasmids for SMN152SH1 and SMN197SH3,
      respectively.

PMID- 29449404
TI  - Draft Genome Assemblies of Xylose-Utilizing Candida tropicalis and Candida
      boidinii with Potential Application in Biochemical and Biofuel Production.
AB  - Non-albicans Candida species are growing in prominence in industrial
      biotechnology due to their ability to utilize hemicellulose. Here, we present the
      draft genome sequences of an inhibitor-tolerant Candida tropicalis strain (Y6604)
      and Candida boidinii NCAIM Y01308T.

PMID- 29449405
TI  - Draft Genome Sequence of Lactobacillus helveticus ATCC 12046.
AB  - Lactobacillus helveticus is a lactic acid bacterium used traditionally in the
      dairy industry, especially in the manufacture of cheeses. We present here the
      2,141,841-bp draft genome sequence of L. helveticus strain ATCC 12046, a
      potential starter strain for improving cheese production.

PMID- 29449406
TI  - Complete Genome Sequence of Mycobacterium sp. Strain 4858.
AB  - Mycobacterium sp. strain 4858 is a nontuberculous mycobacterium isolated from
      sputum in a Cambodian patient with a pulmonary infection. We report the first
      complete 5.6-Mbp-long genome sequence of Mycobacterium strain 4858, with 68.24%
      GC content, carrying 5,255 protein-coding genes, 47 tRNAs, and 3 rRNA genes.

PMID- 29449407
TI  - Complete Genome Sequences of Five Human Respiratory Syncytial Virus Isolates
      Collected in Brazil.
AB  - Here, we present the complete genome sequences of five human respiratory
      syncytial virus isolates collected from hospitalized infants suffering from acute
      respiratory disease. These are the first five complete genome sequences of human
      respiratory syncytial virus to originate from Brazil.

PMID- 29449408
TI  - Enhancer RNA profiling predicts transcription factor activity.
AB  - Transcription factors (TFs) exert their regulatory influence through the binding
      of enhancers, resulting in coordination of gene expression programs. Active
      enhancers are often characterized by the presence of short, unstable transcripts
      termed enhancer RNAs (eRNAs). While their function remains unclear, we
      demonstrate that eRNAs are a powerful readout of TF activity. We infer sites of
      eRNA origination across hundreds of publicly available nascent transcription data
      sets and show that eRNAs initiate from sites of TF binding. By quantifying the
      colocalization of TF binding motif instances and eRNA origins, we derive a simple
      statistic capable of inferring TF activity. In doing so, we uncover dozens of
      previously unexplored links between diverse stimuli and the TFs they affect.

PMID- 29449409
TI  - A human-specific switch of alternatively spliced AFMID isoforms contributes to
      TP53 mutations and tumor recurrence in hepatocellular carcinoma.
AB  - Pre-mRNA splicing can contribute to the switch of cell identity that occurs in
      carcinogenesis. Here, we analyze a large collection of RNA-seq data sets and
      report that splicing changes in hepatocyte-specific enzymes, such as AFMID and
      KHK, are associated with HCC patients' survival and relapse. The switch of AFMID
      isoforms is an early event in HCC development and is associated with driver
      mutations in TP53 and ARID1A The switch of AFMID isoforms is human-specific and
      not detectable in other species, including primates. Finally, we show that
      overexpression of the full-length AFMID isoform leads to a higher NAD+ level,
      lower DNA-damage response, and slower cell growth in HepG2 cells. The integrative
      analysis uncovered a mechanistic link between splicing switches, de novo NAD+
      biosynthesis, driver mutations, and HCC recurrence.

PMID- 29449410
TI  - Conserved microRNA targeting reveals preexisting gene dosage sensitivities that
      shaped amniote sex chromosome evolution.
AB  - Mammalian X and Y Chromosomes evolved from an ordinary autosomal pair. Genetic
      decay of the Y led to X Chromosome inactivation (XCI) in females, but some Y
      linked genes were retained during the course of sex chromosome evolution, and
      many X-linked genes did not become subject to XCI. We reconstructed gene-by-gene
      dosage sensitivities on the ancestral autosomes through phylogenetic analysis of
      microRNA (miRNA) target sites and compared these preexisting characteristics to
      the current status of Y-linked and X-linked genes in mammals. Preexisting
      heterogeneities in dosage sensitivity, manifesting as differences in the extent
      of miRNA-mediated repression, predicted either the retention of a Y homolog or
      the acquisition of XCI following Y gene decay. Analogous heterogeneities among
      avian Z-linked genes predicted either the retention of a W homolog or gene
      specific dosage compensation following W gene decay. Genome-wide analyses of
      human copy number variation indicate that these heterogeneities consisted of
      sensitivity to both increases and decreases in dosage. We propose a model of
      XY/ZW evolution incorporating such preexisting dosage sensitivities in
      determining the evolutionary fates of individual genes. Our findings thus provide
      a more complete view of the role of dosage sensitivity in shaping the mammalian
      and avian sex chromosomes and reveal an important role for post-transcriptional
      regulatory sequences (miRNA target sites) in sex chromosome evolution.

PMID- 29449412
TI  - Hemodynamic Characteristics in Significant Symptomatic and Asymptomatic Primary
      Mitral Valve Regurgitation at Rest and During Exercise.
AB  - BACKGROUND: In severe asymptomatic primary mitral valve regurgitation without
      risk factors, surgery strategy is controversial. We sought to clarify whether
      being symptomatic corresponds to the hemodynamic burden and reduced exercise
      capacity. A better understanding of this may contribute to optimize timing of
      surgery. METHODS AND RESULTS: Subjects with asymptomatic (New York Heart
      Association functional class I, n=29) or symptomatic (New York Heart Association
      functional class II and III, n=28) significant primary mitral valve regurgitation
      (effective regurgitant orifice, >=0.30 cm2; left ventricular ejection fraction,
      >60%) were included. Right heart catheterization during rest and exercise,
      echocardiography, magnetic resonance imaging, and peak oxygen consumption test
      was performed. Symptomatic subjects had significantly higher pulmonary capillary
      wedge pressure at rest (14+/-4 versus 11+/-3 mm Hg; P=0.003) and at maximal
      exercise (30+/-6 versus 25+/-7 mm Hg; P=0.02) and higher mean pulmonary artery
      pressure (PAP) at rest (22+/-7 versus 18+/-4 mm Hg; P=0.005) and maximal exercise
      (46+/-8 versus 39+/-7 mm Hg; P=0.005) than asymptomatic subjects. Among
      asymptomatic subjects with normal resting value, exercise testing revealed a
      systolic PAP >60 mm Hg in 34%. Also the reverse response with minimal increase in
      pulmonary capillary wedge pressure and mean PAP during exercise was seen,
      especially in asymptomatic subjects. Among symptomatic subjects, we found a
      significant inverse correlation between resting mean PAP and left ventricular
      ejection fraction (r=-0.52; P=0.02) and right ventricular ejection fraction (r=
      0.67; P<0.01). Peak oxygen consumption was equal and normal in both groups and
      correlated with left ventricular stroke volume but not with pulmonary capillary
      wedge pressure. CONCLUSIONS: Symptoms in patients with severe mitral valve
      regurgitation relate to congestion (pulmonary capillary wedge pressure and PAP),
      but not to peak oxygen consumption, which is determined by forward left
      ventricular stroke volume. Exercise testing reveals a higher mitral valve
      regurgitation burden in apparently asymptomatic patients. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02961647.

PMID- 29449411
TI  - Molecular Imaging in Drug Discovery and Development.
AB  - Noninvasive imaging has played an increasing role in the process of
      cardiovascular drug development. This review focuses specifically on the use of
      molecular imaging, which has been increasingly applied to improve and accelerate
      certain preclinical steps in drug development, including the identification of
      appropriate therapeutic targets, evaluation of on-target and off-target effects
      of candidate therapies, assessment of dose response, and the evaluation of drug
      or biological biodistribution and pharmacodynamics. Unlike the case in cancer
      medicine, in cardiovascular medicine, molecular imaging has not been used as a
      primary surrogate clinical end point for drug approval. However, molecular
      imaging has been applied in early clinical trials, particularly in phase 0
      studies, to demonstrate proof-of-concept or to explain variation in treatment
      effect. Many of these applications where molecular imaging has been used in drug
      development have involved the retasking of technologies that were originally
      intended as clinical diagnostics. With greater experience and recognition of the
      rich information provided by in vivo molecular imaging, it is anticipated that it
      will increasingly be used to address the enormous time and costs associated with
      bringing a new drug to clinical launch.

PMID- 29449413
TI  - Hemodynamics in Primary Mitral Regurgitation: Support for and Challenges to the
      Conventional Wisdom.

PMID- 29449416
TI  - Correction: Differential Toxicity in Patients with and without DNA Repair
      Mutations: Phase I Study of Carboplatin and Talazoparib in Advanced Solid Tumors.

PMID- 29449418
TI  - The antiphospholipid syndrome and its 'non-criteria' manifestations.

PMID- 29449419
TI  - Reversible cerebellar oedema secondary to profound hypomagnesaemia.
AB  - Magnesium is the second most abundant intracellular cation. Deficiency can cause
      several neurological complications, including cerebellar syndromes, with various
      MRI findings. These include cerebellar oedema, presumably through a similar
      mechanism to that in posterior reversible encephalopathy syndrome (PRES). People
      particularly vulnerable to deficiency include those with high alcohol
      consumption, excessive loss due to gastrointestinal pathology and those taking
      certain medications, including proton pump inhibitors. We report three patients
      with cerebellar syndromes associated with hypomagnesaemia. These cases support
      the previously reported association between hypomagnesaemia and reversible
      cerebellar dysfunction and illustrate the range of potential presentations. They
      highlight an uncommon but treatable cause of cerebellar ataxia that may present
      to acute neurological liaison services.

PMID- 29449414
TI  - Pathogen Trojan Horse Delivers Bioactive Host Protein to Alter Maize Anther Cell
      Behavior in Situ.
AB  - Small proteins are crucial signals during development, host defense, and
      physiology. The highly spatiotemporal restricted functions of signaling proteins
      remain challenging to study in planta. The several month span required to assess
      transgene expression, particularly in flowers, combined with the uncertainties
      from transgene position effects and ubiquitous or overexpression, makes
      monitoring of spatiotemporally restricted signaling proteins lengthy and
      difficult. This situation could be rectified with a transient assay in which
      protein deployment is tightly controlled spatially and temporally in planta to
      assess protein functions, timing, and cellular targets as well as to facilitate
      rapid mutagenesis to define functional protein domains. In maize (Zea mays),
      secreted ZmMAC1 (MULTIPLE ARCHESPORIAL CELLS1) was proposed to trigger somatic
      niche formation during anther development by participating in a ligand-receptor
      module. Inspired by Homer's Trojan horse myth, we engineered a protein delivery
      system that exploits the secretory capabilities of the maize smut fungus Ustilago
      maydis, to allow protein delivery to individual cells in certain cell layers at
      precise time points. Pathogen-supplied ZmMAC1 cell-autonomously corrected both
      somatic cell division and differentiation defects in mutant Zmmac1-1 anthers.
      These results suggest that exploiting host-pathogen interactions may become a
      generally useful method for targeting host proteins to cell and tissue types to
      clarify cellular autonomy and to analyze steps in cell responses.

PMID- 29449420
TI  - Childhood Stature and Growth in Relation to First Ischemic Stroke or
      Intracerebral Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Attained height, an indicator of genetic potential and
      childhood growth environment, is inversely associated with stroke, but the
      mechanisms are poorly understood. We investigated whether childhood height and
      growth are associated with ischemic stroke (IS) and intracerebral hemorrhage
      (ICH). METHODS: In a cohort of Danish schoolchildren born 1930 to 1989, with
      measured height from 7 to 13 years, we investigated associations of childhood
      stature and growth with risks of adult IS and ICH. Cox proportional hazards
      regressions were performed to estimate hazard ratios (HRs) with CIs separately
      for women and men. RESULTS: Among 311 009 individuals, 10 412 were diagnosed with
      IS and 2546 with ICH. Height at 7 years was inversely and significantly
      associated with IS in both sexes (per z score, equivalent to ~5.2 cm in women and
      5.1 cm in men; women: HR=0.89 [95% CI: 0.87-0.92]; men: HR=0.90 [95% CI: 0.88
      0.92]) and with ICH in men (HR=0.89 [95% CI: 0.84-0.94]) but not in women
      (HR=0.97 [95% CI: 0.91-1.04]). Associations were similar at older childhood ages
      and were stable throughout the study period. No statistically significant
      associations for growth from 7 to 13 years were observed for IS or ICH.
      CONCLUSIONS: Short stature at 7 to 13 years is significantly associated with
      increased risks of IS in both sexes and with ICH in men. Growth during this
      period of childhood is not significantly associated with either of these stroke
      subtypes, suggesting that underlying mechanisms linking height with risks of
      stroke may exert their influence already by early childhood.

PMID- 29449421
TI  - Increased T-helper 17.1 cells in sarcoidosis mediastinal lymph nodes.
AB  - The lung-draining mediastinal lymph nodes (MLNs) are currently widely used to
      diagnose sarcoidosis. We previously reported that T-helper (Th) 17.1 cells are
      responsible for the exaggerated interferon-gamma production in sarcoidosis lungs.
      In this study, we aimed to investigate 1) whether Th17.1 cells are also increased
      in the MLNs of sarcoidosis patients and 2) whether frequencies of the Th17.1
      cells at diagnosis may correlate with disease progression.MLN cells from
      treatment-naive pulmonary sarcoidosis patients (n=17) and healthy controls (n=22)
      and peripheral blood mononuclear cells (n=34) and bronchoalveolar lavage fluid
      (BALF) (n=36) from sarcoidosis patients were examined for CD4+ T-cell subset
      proportions using flow cytometry.Higher proportions of Th17.1 cells were detected
      in sarcoidosis MLNs than in control MLNs. Higher Th17.1 cell proportions were
      found in sarcoidosis BALF compared with MLNs and peripheral blood. Furthermore,
      BALF Th17.1 cell proportions were significantly higher in patients developing
      chronic disease than in patients undergoing resolution within 2 years of clinical
      follow-up.These data suggest that Th17.1 cell proportions in pulmonary
      sarcoidosis can be evaluated as a diagnostic and/or prognostic marker in clinical
      practice and could serve as a new therapeutic target.

PMID- 29449422
TI  - Safety and efficacy of pirfenidone in patients carrying telomerase complex
      mutation.

PMID- 29449423
TI  - The effects of electronic cigarette vapour on the lung: direct comparison to
      tobacco smoke.

PMID- 29449425
TI  - Young and middle-aged adults with airflow limitation according to lower limit of
      normal but not fixed ratio have high morbidity and poor survival: a population
      based prospective cohort study.
AB  - A presumed consequence of using a fixed ratio for the definition of airflow
      limitation (AFL) has been overdiagnosis among older individuals and
      underdiagnosis among younger individuals. However, the prognosis of younger
      individuals with potentially underdiagnosed AFL is poorly described. We
      hypothesised that potential underdiagnosis of AFL at a younger age is associated
      with poor prognosis.We assigned 95 288 participants aged 20-100 years from the
      Copenhagen General Population Study into the following groups: individuals
      without AFL with forced expiratory volume in 1 s (FEV1)/forced vital capacity
      (FVC) >=0.70 and >=lower limit of normal (LLN) (n=78 779, 83%); individuals with
      potentially underdiagnosed AFL with FEV1/FVC >=0.70 and <LLN (n=1056, 1%);
      individuals with potentially overdiagnosed AFL with FEV1/FVC <0.70 and >=LLN
      (n=3088, 3%); and individuals with AFL with FEV1/FVC <0.70 and <LLN (n=12 365,
      13%). We assessed risk of exacerbations, pneumonias, ischaemic heart disease,
      heart failure and all-cause mortality. Median follow-up was 6.0 years (range: 2
      days-11 years).Compared to individuals without AFL, individuals with potentially
      underdiagnosed AFL had an increased risk of morbidity and mortality with age- and
      sex-adjusted hazard ratios (HR) of 2.7 (95% CI: 1.7-4.5) for pneumonias, 2.3 (95%
      CI: 1.2-4.5) for heart failure, and 3.1 (95% CI: 2.1-4.6) for all-cause
      mortality.Young and middle-aged adults with AFL according to LLN but not fixed
      ratio experience increased respiratory and cardiovascular morbidity and early
      death.

PMID- 29449424
TI  - Sex differences in the associations of obstructive sleep apnoea with
      epidemiological factors.
AB  - Despite the well-known male predominance in the prevalence of obstructive sleep
      apnoea (OSA), sex differences in the associations between OSA and a comprehensive
      range of epidemiological factors remain less clear.We examined the prevalence of
      self-reported OSA in 143 326 females (age 48-93 years) from the Nurses' Health
      Study (NHS) and NHS-II and 22 896 males from the Health Professionals Follow-up
      Study (age 65-101 years) in 2012-2013. Multivariable logistic regression was used
      to estimate the sex-specific prevalence odds ratios (pOR) and 95% confidence
      intervals of OSA by demographic, anthropometric, lifestyle and comorbidity
      factors.The overall prevalence of self-reported OSA was 6.4% in females and 13.8%
      in males. After mutual adjustment, the associations of OSA with physical
      inactivity, hypertension and daytime sleepiness were stronger in females, whereas
      the associations with waist circumference and witnessed apnoea were stronger in
      males (p-heterogeneity <0.01). There were qualitative sex differences in the
      associations with age (pOR per 5-year increment in females 0.95, 95% CI 0.94
      0.96, and males 1.04, 1.01-1.08; p-heterogeneity <0.0001) and marital status (pOR
      for married versus other in females 0.85, 95% CI 0.81-0.89, and males 1.11, 0.99
      1.25; p-heterogeneity <0.0001).Substantial sex differences exist in the
      associations with various factors, suggesting sex-specific mechanisms in OSA.

PMID- 29449426
TI  - DNA methylation modules in airway smooth muscle are associated with asthma
      severity.

PMID- 29449427
TI  - Neutrophil extracellular trap formation is regulated by CXCR2 in COPD
      neutrophils.

PMID- 29449428
TI  - A novel piperidine identified by stem cell-based screening attenuates pulmonary
      arterial hypertension by regulating BMP2 and PTGS2 levels.
AB  - Genetic defects in bone morphogenetic protein type II receptor (BMPRII)
      signalling and inflammation contribute to the pathogenesis of pulmonary arterial
      hypertension (PAH). The receptor is activated by bone morphogenetic protein (BMP)
      ligands, which also enhance BMPR2 transcription. A small-molecule BMP upregulator
      with selectivity on vascular endothelium would be a desirable therapeutic
      intervention for PAH.We assayed compounds identified in the screening of BMP2
      upregulators for their ability to increase the expression of inhibitor of DNA
      binding 1 (Id1), using a dual reporter driven specifically in human embryonic
      stem cell-derived endothelial cells. These assays identified a novel piperidine,
      BMP upregulator 1 (BUR1), that increased endothelial Id1 expression with a half
      maximal effective concentration of 0.098 MUmol.L-1 Microarray analyses and
      immunoblotting showed that BUR1 induced BMP2 and prostaglandin-endoperoxide
      synthase 2 (PTGS2) expression. BUR1 effectively rescued deficient angiogenesis in
      autologous BMPR2+/R899X endothelial cells generated by CRISPR/Cas9 and patient
      cells.BUR1 prevented and reversed PAH in monocrotaline rats, and restored BMPRII
      downstream signalling and modulated the arachidonic acid pathway in the pulmonary
      arterial endothelium in the Sugen 5416/hypoxia PAH mouse model.In conclusion,
      using stem cell technology we have provided a novel small-molecule compound which
      regulates BMP2 and PTGS2 levels that might be useful for the treatment of PAH.

PMID- 29449430
TI  - A Critical Role for the Nucleus Reuniens in Long-Term, But Not Short-Term
      Associative Recognition Memory Formation.
AB  - Recognition memory for single items requires the perirhinal cortex (PRH), whereas
      recognition of an item and its associated location requires a functional
      interaction among the PRH, hippocampus (HPC), and medial prefrontal cortex
      (mPFC). Although the precise mechanisms through which these interactions are
      effected are unknown, the nucleus reuniens (NRe) has bidirectional connections
      with each regions and thus may play a role in recognition memory. Here we
      investigated, in male rats, whether specific manipulations of NRe function
      affected performance of recognition memory for single items, object location, or
      object-in-place associations. Permanent lesions in the NRe significantly impaired
      long-term, but not short-term, object-in-place associative recognition memory,
      whereas single item recognition memory and object location memory were
      unaffected. Temporary inactivation of the NRe during distinct phases of the
      object-in-place task revealed its importance in both the encoding and retrieval
      stages of long-term associative recognition memory. Infusions of specific
      receptor antagonists showed that encoding was dependent on muscarinic and
      nicotinic cholinergic neurotransmission, whereas NMDA receptor neurotransmission
      was not required. Finally, we found that long-term object-in-place memory
      required protein synthesis within the NRe. These data reveal a specific role for
      the NRe in long-term associative recognition memory through its interactions with
      the HPC and mPFC, but not the PRH. The delay-dependent involvement of the NRe
      suggests that it is not a simple relay station between brain regions, but,
      rather, during high mnemonic demand, facilitates interactions between the mPFC
      and HPC, a process that requires both cholinergic neurotransmission and protein
      synthesis.SIGNIFICANCE STATEMENT Recognizing an object and its associated
      location, which is fundamental to our everyday memory, requires specific
      hippocampal-cortical interactions, potentially facilitated by the nucleus
      reuniens (NRe) of the thalamus. However, the role of the NRe itself in
      associative recognition memory is unknown. Here, we reveal the crucial role of
      the NRe in encoding and retrieval of long-term object-in-place memory, but not
      for remembrance of an individual object or individual location and such
      involvement is cholinergic receptor and protein synthesis dependent. This is the
      first demonstration that the NRe is a key node within an associative recognition
      memory network and is not just a simple relay for information within the network.
      Rather, we argue, the NRe actively modulates information processing during long
      term associative memory formation.

PMID- 29449429
TI  - Heterogeneous Origins of Human Sleep Spindles in Different Cortical Layers.
AB  - Sleep spindles are a cardinal feature in human NREM sleep and may be important
      for memory consolidation. We studied the intracortical organization of spindles
      in men and women by recording spontaneous sleep spindles from different cortical
      layers using linear microelectrode arrays. Two patterns of spindle generation
      were identified using visual inspection, and confirmed with factor analysis.
      Spindles (10-16 Hz) were largest and most common in upper and middle channels,
      with limited involvement of deep channels. Many spindles were observed in only
      upper or only middle channels, but approximately half occurred in both. In
      spindles involving both middle and upper channels, the spindle envelope onset in
      middle channels led upper by ~25-50 ms on average. The phase relationship between
      spindle waves in upper and middle channels varied dynamically within spindle
      epochs, and across individuals. Current source density analysis demonstrated that
      upper and middle channel spindles were both generated by an excitatory
      supragranular current sink while an additional deep source was present for middle
      channel spindles only. Only middle channel spindles were accompanied by deep low
      (25-50 Hz) and high (70-170 Hz) gamma activity. These results suggest that upper
      channel spindles are generated by supragranular pyramids, and middle channel by
      infragranular. Possibly, middle channel spindles are generated by core
      thalamocortical afferents, and upper channel by matrix. The concurrence of these
      patterns could reflect engagement of cortical circuits in the integration of more
      focal (core) and distributed (matrix) aspects of memory. These results
      demonstrate that at least two distinct intracortical systems generate human sleep
      spindles.SIGNIFICANCE STATEMENT Bursts of ~14 Hz oscillations, lasting ~1 s, have
      been recognized for over 80 years as cardinal features of mammalian sleep. Recent
      findings suggest that they play a key role in organizing cortical activity during
      memory consolidation. We used linear microelectrode arrays to study their
      intracortical organization in humans. We found that spindles could be divided
      into two types. One mainly engages upper layers of the cortex, which are
      considered to be specialized for associative activity. The other engages both
      upper and middle layers, including those devoted to sensory input. The
      interaction of these two spindle types may help organize the interaction of
      sensory and associative aspects of memory consolidation.

PMID- 29449431
TI  - Wilson disease: more than meets the eye.
AB  - Wilson disease is a rare but important disorder of copper metabolism, with a
      failure to excrete copper appropriately into bile. It is a multisystem condition
      with presentations across all branches of medicine. Diagnosis can be difficult
      and requires a high index of suspicion. It should be considered in unexplained
      liver disease particularly where neuropsychiatric features are also present.
      Treatments are available for all stages of disease. A particularly important
      presentation not to overlook is acute liver failure which carries a high
      mortality risk and may require urgent liver transplantation. Here, we provide an
      overview of this complex condition.

PMID- 29449432
TI  - Different Modes of Negative Regulation of Plant Immunity by Calmodulin-Related
      Genes.
AB  - Plant immune responses activated through the perception of microbe-associated
      molecular patterns, leading to pattern-triggered immunity, are tightly regulated.
      This results in low immune responses in the absence of pathogens and a rapid
      return to the resting state following an activation event. Here, we show that two
      CALMODULIN-LIKE genes, CML46 and CML47, negatively regulate salicylic acid
      accumulation and immunity in Arabidopsis (Arabidopsis thaliana). The double
      mutant cml46 cml47 is highly resistant to the pathogen Pseudomonas syringae pv
      maculicola (Pma). The effects of cml46 cml47 on Pma growth are genetically
      additive to that of cbp60a, a known negative regulator in the CALMODULIN-BINDING
      PROTEIN60 (CBP60) family. Transcriptome profiling revealed the effects of cbp60a
      and cml46 cml47 on both common and separate sets of genes, with the majorities of
      these differentially expressed genes being Pma responsive. CBP60g, a positive
      regulator of immunity in the CBP60 family, was found to be transcriptionally
      regulated by CBP60a, CML46, and CML47 Analysis of the flg22-induced mRNA levels
      of CBP60g in cbp60a and cml46 cml47 revealed that cml46 cml47 plants have higher
      induced expression while cbp60a plants retain elevated levels longer than wild
      type plants. Assays for the effect of flg22 treatment on Pma growth showed that
      the effect is stronger in cml46 cml47 plants and lasts longer in cbp60a plants.
      Thus, the expression pattern of CBP60g is reflected in flg22-induced resistance
      to Pma.

PMID- 29449433
TI  - Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra
      stable chronic lymphocytic leukemia with low frequency of driver mutations.
AB  - Despite the recent discovery of recurrent driver mutations in chronic lymphocytic
      leukemia, the genetic factors involved in disease onset remain largely unknown.
      To address this issue, we performed whole-genome sequencing in 11 individuals
      with monoclonal B- cell lymphocytosis, both of the low-count and high-count
      subtypes, and 5 patients with ultra-stable chronic lymphocytic leukemia (>10
      years without progression from initial diagnosis). All three entities were
      indistinguishable at the genomic level exhibiting low genomic complexity and
      similar types of somatic mutations. Exonic mutations were not frequently
      identified in putative chronic lymphocytic leukemia driver genes in all settings,
      including low-count monoclonal B-cell lymphocytosis. To corroborate these
      findings, we also performed deep sequencing in 11 known frequently mutated genes
      in an extended cohort of 28 monoclonal B-cell lymphocytosis/chronic lymphocytic
      leukemia cases. Interestingly, shared mutations were detected between clonal B
      cells and paired polymorphonuclear cells, strengthening the notion that at least
      a fraction of somatic mutations may occur before disease onset, likely at the
      hematopoietic stem cell level. Finally, we identified previously unreported non
      coding variants targeting pathways relevant to B-cell and chronic lymphocytic
      leukemia development, likely associated with the acquisition of the
      characteristic neoplastic phenotype typical of both monoclonal B-cell
      lymphocytosis and chronic lymphocytic leukemia.

PMID- 29449435
TI  - Novel hereditary spherocytosis-associated splice site mutation in the ANK1 gene
      caused by parental gonosomal mosaicism.

PMID- 29449434
TI  - MSH6 haploinsufficiency at relapse contributes to the development of thiopurine
      resistance in pediatric B-lymphoblastic leukemia.
AB  - Survival of children with relapsed acute lymphoblastic leukemia is poor, and
      understanding mechanisms underlying resistance is essential to developing new
      therapy. Relapse-specific heterozygous deletions in MSH6, a crucial part of DNA
      mismatch repair, are frequently detected. Our aim was to determine whether MSH6
      deletion results in a hypermutator phenotype associated with generation of
      secondary mutations involved in drug resistance, or if it leads to a failure to
      initiate apoptosis directly in response to chemotherapeutic agents. We knocked
      down MSH6 in mismatch repair proficient cell lines (697 and UOCB1) and showed
      significant increases in IC50s to 6-thioguanine and 6-mercaptopurine (697: 26-
      and 9-fold; UOCB1: 5- and 8-fold) in vitro, as well as increased resistance to 6
      mercaptopurine treatment in vivo No shift in IC50 was observed in deficient cells
      (Reh and RS4;11). 697 MSH6 knockdown resulted in increased DNA thioguanine
      nucleotide levels compared to non-targeted cells (3070 vs 1722 fmol/MUg DNA) with
      no difference observed in mismatch repair deficient cells. Loss of MSH6 did not
      give rise to microsatellite instability in cell lines or clinical samples, nor
      did it significantly increase mutation rate, but rather resulted in a defect in
      cell cycle arrest upon thiopurine exposure. MSH6 knockdown cells showed minimal
      activation of checkpoint regulator CHK1, gammaH2AX (DNA damage marker) and p53
      levels upon treatment with thiopurines, consistent with intrinsic chemoresistance
      due to failure to recognize thioguanine nucleotide mismatching and initiate
      mismatch repair. Aberrant MSH6 adds to the list of alterations/mutations
      associated with acquired resistance to purine analogs emphasizing the importance
      of thiopurine therapy.

PMID- 29449436
TI  - Mixed-species RNAseq analysis of human lymphoma cells adhering to mouse stromal
      cells identifies a core gene set that is also differentially expressed in the
      lymph node microenvironment of mantle cell lymphoma and chronic lymphocytic
      leukemia patients.
AB  - A subset of hematologic cancer patients is refractory to treatment or suffers
      relapse, due in part to minimal residual disease, whereby some cancer cells
      survive treatment. Cell-adhesion-mediated drug resistance is an important
      mechanism, whereby cancer cells receive survival signals via interaction with
      e.g. stromal cells. No genome-wide studies of in vitro systems have yet been
      performed to compare gene expression in different cell subsets within a co
      culture and cells grown separately. Using RNA sequencing and species-specific
      read mapping, we compared transcript levels in human Jeko-1 mantle cell lymphoma
      cells stably adhered to mouse MS-5 stromal cells or in suspension within a co
      culture or cultured separately as well as in stromal cells in co-culture or in
      separate culture. From 1050 differentially expressed transcripts in adherent
      mantle cell lymphoma cells, we identified 24 functional categories that together
      represent four main functional themes, anti-apoptosis, B-cell signaling, cell
      adhesion/migration and early mitosis. A comparison with previous mantle cell
      lymphoma and chronic lymphocytic leukemia studies, of gene expression differences
      between lymph node and blood, identified 116 genes that are differentially
      expressed in all three studies. From these genes, we suggest a core set of genes
      (CCL3, CCL4, DUSP4, ETV5, ICAM1, IL15RA, IL21R, IL4I1, MFSD2A, NFKB1, NFKBIE,
      SEMA7A, TMEM2) characteristic of cells undergoing cell-adhesion-mediated
      microenvironment signaling in mantle cell lymphoma/chronic lymphocytic leukemia.
      The model system developed and characterized here together with the core gene set
      will be useful for future studies of pathways that mediate increased cancer cell
      survival and drug resistance mechanisms.

PMID- 29449438
TI  - Gene expression signature of the ageing lung: breathing new life into COPD.

PMID- 29449439
TI  - Macrophages and neutrophils: dynamic duo or partners in crime?

PMID- 29449437
TI  - Dynamic clonal progression in xenografts of acute lymphoblastic leukemia with
      intrachromosomal amplification of chromosome 21.
AB  - Intrachromosomal amplification of chromosome 21 is a heterogeneous chromosomal
      rearrangement occurring in 2% of cases of childhood precursor B-cell acute
      lymphoblastic leukemia. These abnormalities are too complex to engineer
      faithfully in animal models and are unrepresented in leukemia cell lines. As a
      resource for future functional and preclinical studies, we have created
      xenografts from the leukemic blasts of patients with intrachromosomal
      amplification of chromosome 21 and characterized them by in-vivo and ex-vivo
      luminescent imaging, flow immunophenotyping, and histological and ultrastructural
      analyses of bone marrow and the central nervous system. Investigation of up to
      three generations of xenografts revealed phenotypic evolution, branching genomic
      architecture and, compared with other B-cell acute lymphoblastic leukemia genetic
      subtypes, greater clonal diversity of leukemia-initiating cells. In support of
      intrachromosomal amplification of chromosome 21 as a primary genetic abnormality,
      it was always retained through generations of xenografts, although we also
      observed the first example of structural evolution of this rearrangement. Clonal
      segregation in xenografts revealed convergent evolution of different secondary
      genomic abnormalities implicating several known tumor suppressor genes and a
      region, containing the B-cell adaptor, PIK3AP1, and nuclear receptor co
      repressor, LCOR, in the progression of B-cell acute lymphoblastic leukemia.
      Tracking of mutations in patients and derived xenografts provided evidence for co
      operation between abnormalities activating the RAS pathway in B-cell acute
      lymphoblastic leukemia and for their aggressive clonal expansion in the xeno
      environment. Bi-allelic loss of the CDKN2A/B locus was recurrently maintained or
      emergent in xenografts and also strongly selected as RNA sequencing demonstrated
      a complete absence of reads for genes associated with the deletions.

PMID- 29449440
TI  - Lung clearance index to monitor treatment response in pulmonary exacerbations in
      preschool children with cystic fibrosis.
AB  - BACKGROUND: Antibiotic treatment for pulmonary symptoms in preschool children
      with cystic fibrosis (CF) varies among clinicians. The lung clearance index (LCI)
      is sensitive to early CF lung disease, but its utility to monitor pulmonary
      exacerbations in young children has not been assessed. OBJECTIVE: We aim to (1)
      understand how LCI changes during lower respiratory tract symptoms relative to a
      recent clinically stable measurement, (2) determine whether LCI can identify
      antibiotic treatment response and (3) compare LCI changes to changes in
      spirometric indices. METHODS: LCI and spirometry were measured at quarterly
      clinic visits over a 12-month period in preschool children with CF. Symptomatic
      visits were identified and classified as treated or untreated. Treatment response
      was estimated using propensity score matching methods. RESULTS: 104 symptomatic
      visits were identified in 78 participants. LCI increased from baseline in both
      treated (mean relative change +23.8% (95% CI 16.2 to 31.4)) and untreated
      symptomatic visits (mean relative change +11.2% (95% CI 2.4 to 19.9)). A
      significant antibiotic treatment effect was observed when LCI was used as the
      outcome measure (average treatment effect -15.5% (95% CI -25.4 to -5.6)) but not
      for z-score FEV1. CONCLUSION: LCI significantly deteriorated with pulmonary
      symptoms relative to baseline and improved with antibiotic treatment. These data
      suggest that LCI may have a role in the routine clinical care of preschool
      children with CF.

PMID- 29449441
TI  - Role of NADPH oxidase-2 and oxidative stress in children exposed to passive
      smoking.
AB  - This study explored oxidative stress, nicotinamide adenine dinucleotide phosphate
      oxidase-2 (Nox2) activity and endothelial function in children exposed or not to
      passive smoking. Compared with controls (n=57), Nox2 activity and isoprostanes
      were higher in children exposed to passive smoking (n=57); conversely, nitric
      oxide (NO) bioavailability and flow-mediated dilation were lower in children
      exposed to passive smoking. A bivariate analysis showed that Nox2 activity
      correlated with flow-mediated dilation, NO bioavailability and isoprostanes. A
      multivariate analysis showed that Nox2 activity was significantly associated with
      serum isoprostanes and cotinine levels; flow-mediated dilation was associated
      with isoprostanes and carotid intima-media thickness.In children exposed to
      passive smoking, Nox2-derived oxidative stress is upregulated and inversely
      associated with impaired artery dilation.

PMID- 29449442
TI  - Design and Rationale of the RIPCORD 2 Trial (Does Routine Pressure Wire
      Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of
      Chest Pain?): A Randomized Controlled Trial to Compare Routine Pressure Wire
      Assessment With Conventional Angiography in the Management of Patients With
      Coronary Artery Disease.
AB  - BACKGROUND: Investigation of anginal chest pain has traditionally involved either
      assessment of the coronary anatomy by angiography or noninvasive testing for
      reversible ischemia. Invasive pressure wire assessment at the time of angiography
      offers information on both anatomy and physiology. Fractional flow reserve-guided
      percutaneous coronary intervention is associated with lower resource utilization
      and improved clinical outcome compared with angiographic guidance alone. However,
      the value of routine fractional flow reserve of all major coronary vessels at the
      time of diagnostic angiography has not been established in a randomized trial
      despite persuasive observational data. A change in practice to routine fractional
      flow reserve assessment of all major vessels during diagnostic angiography would
      require evidence not just of clinical benefit but also of cost effectiveness.
      This randomized trial aims to test that strategy. METHODS AND RESULTS: RIPCORD 2
      (Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary
      Angiography for Diagnosis of Chest Pain?) is an 1100 patient prospective,
      multicenter, randomized trial. Participants are randomized, after initial
      coronary angiography, and in equal proportion, to assessment and management
      according to (1) conventional angiography only or (2) additional routine pressure
      wire assessment in all epicardial vessels of sufficient size to be amenable to
      revascularization. The primary economic outcome measure will be a comparison of
      healthcare costs at 1 year. The primary quality-of-life outcome measure analysis
      will compare patient-reported quality-of-life scores at 1 year. Secondary outcome
      measures include clinical events at 1 year, management strategy (optimal medical
      therapy with or without revascularization), and angina status at 1 year according
      to Canadian Cardiovascular Society angina grade. CONCLUSIONS: The aim of the
      RIPCORD 2 trial is to assess whether a strategy of routine fractional flow
      reserve-guided assessment and management of all major coronary arteries will be
      associated with more effective resource utilization, improved quality of life,
      and better clinical outcome, compared with angiographic guidance alone. CLINICAL
      TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier:
      NCT02892903.

PMID- 29449443
TI  - Sex Differences in Ischemic Heart Disease: Advances, Obstacles, and Next Steps.
AB  - Evolving knowledge of sex-specific presentations, improved recognition of
      conventional and novel risk factors, and expanded understanding of the sex
      specific pathophysiology of ischemic heart disease have resulted in improved
      clinical outcomes in women. Yet, ischemic heart disease continues to be the
      leading cause of morbidity and mortality in women in the United States. The
      important publication by the Institute of Medicine titled "Women's Health
      Research-Progress, Pitfalls, and Promise," highlights the persistent disparities
      in cardiovascular disease burden among subgroups of women, particularly women who
      are socially disadvantaged because of race, ethnicity, income level, and
      educational attainment. These important health disparities reflect
      underrepresentation of women in research, with the resultant unfavorable impact
      on diagnosis, prevention, and treatment strategies in women at risk for
      cardiovascular disease. Causes of disparities are multifactorial and related to
      differences in risk factor prevalence, access to care, use of evidence-based
      guidelines, and social and environmental factors. Lack of awareness in both the
      public and medical community, as well as existing knowledge gap regarding sex
      specific differences in presentation, risk factors, pathophysiology, and response
      to treatment for ischemic heart disease, further contribute to outcome
      disparities. There is a critical need for implementation of sex- and gender
      specific strategies to improve cardiovascular outcomes. This review is tailored
      to meet the needs of a busy clinician and summarizes the contemporary trends,
      characterizes current sex-specific outcome disparities, delineates challenges,
      and proposes transformative solutions for improvement of the full spectrum of
      ischemic heart disease clinical care and research in women.

PMID- 29449444
TI  - Frontiers in Cardiovascular Outcomes Research.

PMID- 29449445
TI  - Evaluation of Penalized-Likelihood Estimation Reconstruction on a Digital Time-of
      Flight PET/CT Scanner for 18F-FDG Whole-Body Examinations.
AB  - The resolution and quantitative accuracy of PET are highly influenced by the
      reconstruction method. Penalized-likelihood estimation algorithms allow for fully
      convergent iterative reconstruction, generating a higher image contrast than
      ordered-subsets expectation maximization (OSEM) while limiting noise. In this
      study, a type of penalized reconstruction known as block-sequential regularized
      expectation maximization (BSREM) was compared with time-of-flight OSEM (TOF
      OSEM). Various strengths of noise penalization factor beta were tested along with
      various acquisition durations and transaxial fields of view (FOVs) with the aim
      of evaluating the performance and clinical use of BSREM for 18F-FDG PET/CT, both
      quantitatively and in a qualitative visual evaluation. Methods: Eleven clinical
      whole-body 18F-FDG PET/CT examinations acquired on a digital TOF PET/CT scanner
      were included. The data were reconstructed using BSREM with point-spread function
      recovery and beta-factors of 133, 267, 400, and 533-and using TOF OSEM with point
      spread function-for various acquisition times per bed position and various FOVs.
      Noise level, signal-to-noise ratio (SNR), signal-to-background ratio (SBR), and
      SUV were analyzed. A masked evaluation of visual image quality, rating several
      aspects, was performed by 2 nuclear medicine physicians to complement the
      analysis. Results: The lowest levels of noise were reached with the highest beta
      factor, resulting in the highest SNR, which in turn resulted in the lowest SBR. A
      beta-factor of 400 gave noise equivalent to TOF OSEM but produced a significant
      increase in SUVmax (11%), SNR (22%), and SBR (12%). BSREM with a beta-factor of
      533 at a decreased acquisition duration (2 min/bed position) was comparable to
      TOF OSEM at a full acquisition duration (3 min/bed position). Reconstructed FOV
      had an impact on BSREM outcome measures; SNR increased and SBR decreased when FOV
      was shifted from 70 to 50 cm. The evaluation of visual image quality resulted in
      similar scores for reconstructions, although a beta-factor of 400 obtained the
      highest mean whereas a beta-factor of 267 was ranked best in overall image
      quality, contrast, sharpness, and tumor detectability. Conclusion: In comparison
      with TOF OSEM, penalized BSREM reconstruction resulted in an increased tumor
      SUVmax and an improved SNR and SBR at a matched level of noise. BSREM allowed for
      a shorter acquisition than TOF OSEM, with equal image quality.

PMID- 29449446
TI  - Improving the Accuracy of Simultaneously Reconstructed Activity and Attenuation
      Maps Using Deep Learning.
AB  - Simultaneous reconstruction of activity and attenuation using the maximum
      likelihood reconstruction of activity and attenuation (MLAA) augmented by time-of
      flight information is a promising method for PET attenuation correction. However,
      it still suffers from several problems, including crosstalk artifacts, slow
      convergence speed, and noisy attenuation maps (MU-maps). In this work, we
      developed deep convolutional neural networks (CNNs) to overcome these MLAA
      limitations, and we verified their feasibility using a clinical brain PET
      dataset. Methods: We applied the proposed method to one of the most challenging
      PET cases for simultaneous image reconstruction (18F-fluorinated-N-3-fluoropropyl
      2-beta-carboxymethoxy-3-beta-(4-iodophenyl)nortropane [18F-FP-CIT] PET scans with
      highly specific binding to striatum of the brain). Three different CNN
      architectures (convolutional autoencoder [CAE], Unet, and Hybrid of CAE) were
      designed and trained to learn a CT-derived MU-map (MU-CT) from the MLAA-generated
      activity distribution and MU-map (MU-MLAA). The PET/CT data of 40 patients with
      suspected Parkinson disease were used for 5-fold cross-validation. For the
      training of CNNs, 800,000 transverse PET and CT slices augmented from 32 patient
      datasets were used. The similarity to MU-CT of the CNN-generated MU-maps (MU-CAE,
      MU-Unet, and MU-Hybrid) and MU-MLAA was compared using Dice similarity
      coefficients. In addition, we compared the activity concentration of specific
      (striatum) and nonspecific (cerebellum and occipital cortex) binding regions and
      the binding ratios in the striatum in the PET activity images reconstructed using
      those MU-maps. Results: The CNNs generated less noisy and more uniform MU-maps
      than the original MU-MLAA. Moreover, the air cavities and bones were better
      resolved in the proposed CNN outputs. In addition, the proposed deep learning
      approach was useful for mitigating the crosstalk problem in the MLAA
      reconstruction. The Hybrid network of CAE and Unet yielded the most similar MU
      maps to MU-CT (Dice similarity coefficient in the whole head = 0.79 in the bone
      and 0.72 in air cavities), resulting in only about a 5% error in activity and
      binding ratio quantification. Conclusion: The proposed deep learning approach is
      promising for accurate attenuation correction of activity distribution in time-of
      flight PET systems.

PMID- 29449447
TI  - Tracers for Fluorescence-Guided Surgery: How Elongation of the Polymethine Chain
      in Cyanine Dyes Alters the Pharmacokinetics of a Dual-Modality c[RGDyK] Tracer.
AB  - The potential of receptor-mediated fluorescence-based image-guided surgery
      tracers is generally linked to the near-infrared emission profile and good
      manufacturing-production availability of fluorescent dyes. Surprisingly, little
      is known about the critical interaction between the structural composition of the
      dyes and the pharmacokinetics of the tracers. In this study, a dual-modality
      tracer design was used to systematically and quantitatively evaluate the
      influence of elongation of the polymethine chain in a fluorescent cyanine dye on
      the imaging potential of a targeted tracer. Methods: As a model system, the
      integrin marker alphavbeta3 was targeted using arginylglycylaspartisc acid [RGD]
      based vectors functionalized with a 111In-diethylenetriaminepentaacetic acid
      (DTPA) chelate and a fluorescent dye: (Cy3-(SO3)methyl-COOH [emission wavelength
      (lambdaem), 580 nm], Cy5-(SO3)methyl-COOH [lambdaem, 680 nm], or Cy7-(SO3)methyl
      COOH [lambdaem, 780 nm]). Tracers were analyzed for differences in photophysical
      properties, serum protein binding, chemical or optical stability, and signal
      penetration through tissue. Receptor affinities were evaluated using saturation
      and competition experiments. In vivo biodistribution (SPECT imaging and
      percentage injected dose per gram of tissue) was assessed in tumor-bearing mice
      and complemented with in vivo and ex vivo fluorescence images obtained using a
      clinical-grade multispectral fluorescence laparoscope. Results: Two carbon-atom
      step variations in the polymethine chain of the fluorescent cyanine dyes were
      shown to significantly influence the chemical and photophysical characteristics
      (e.g., stability, brightness, and tissue penetration) of the hybrid RGD tracers.
      DTPA-Cy5-(SO3)methyl-COOH-c[RGDyK] structurally outperformed its Cy3 and Cy7
      derivatives. Radioactivity-based evaluation of in vivo tracer pharmacokinetics
      yielded the lowest nonspecific uptake and highest tumor-to-background ratio for
      DTPA-Cy5-(SO3)methyl-COOH-c[RGDyK] (13.2 +/- 1.7), with the Cy3 and Cy7 analogs
      trailing at respective tumor-to-background ratios of 5.7 +/- 0.7 and 4.7 +/- 0.7.
      Fluorescence-based assessment of tumor visibility revealed a similar trend.
      Conclusion: These findings underline that variations in the polymethine chain
      lengths of cyanine dyes have a profound influence on the photophysical
      properties, stability, and in vivo targeting capabilities of fluorescent imaging
      tracers. In a direct comparison, the intermediate-length dye (Cy5) yielded a
      superior c[RGDyK] tracer, compared with the shorter (Cy3) and longer (Cy7)
      analogs.

PMID- 29449448
TI  - 6"-18F-Fluoromaltotriose PET Evaluation in Escherichia Coli-Induced Myositis: Is
      There Uptake Saturation in Control?

PMID- 29449450
TI  - The Era of Human Developmental Nephrology.

PMID- 29449449
TI  - Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the
      Cortical Nephrogenic Niche of the Human and Mouse Kidney.
AB  - Cellular interactions among nephron, interstitial, and collecting duct
      progenitors drive mammalian kidney development. In mice, Six2+ nephron progenitor
      cells (NPCs) and Foxd1+ interstitial progenitor cells (IPCs) form largely
      distinct lineage compartments at the onset of metanephric kidney development.
      Here, we used the method for analyzing RNA following intracellular sorting
      (MARIS) approach, single-cell transcriptional profiling, in situ hybridization,
      and immunolabeling to characterize the presumptive NPC and IPC compartments of
      the developing human kidney. As in mice, each progenitor population adopts a
      stereotypical arrangement in the human nephron-forming niche: NPCs capped
      outgrowing ureteric branch tips, whereas IPCs were sandwiched between the NPCs
      and the renal capsule. Unlike mouse NPCs, human NPCs displayed a transcriptional
      profile that overlapped substantially with the IPC transcriptional profile, and
      key IPC determinants, including FOXD1, were readily detected within SIX2+ NPCs.
      Comparative gene expression profiling in human and mouse Six2/SIX2+ NPCs showed
      broad agreement between the species but also identified species-biased expression
      of some genes. Notably, some human NPC-enriched genes, including DAPL1 and
      COL9A2, are linked to human renal disease. We further explored the cellular
      diversity of mesenchymal cell types in the human nephrogenic niche through single
      cell transcriptional profiling. Data analysis stratified NPCs into two main
      subpopulations and identified a third group of differentiating cells. These
      findings were confirmed by section in situ hybridization with novel human NPC
      markers predicted through the single-cell studies. This study provides a
      benchmark for the mesenchymal progenitors in the human nephrogenic niche and
      highlights species-variability in kidney developmental programs.

PMID- 29449451
TI  - Conserved and Divergent Molecular and Anatomic Features of Human and Mouse
      Nephron Patterning.
AB  - The nephron is the functional unit of the kidney, but the mechanism of nephron
      formation during human development is unclear. We conducted a detailed analysis
      of nephron development in humans and mice by immunolabeling, and we compared
      human and mouse nephron patterning to describe conserved and divergent features.
      We created protein localization maps that highlight the emerging patterns along
      the proximal-distal axis of the developing nephron and benchmark expectations for
      localization of functionally important transcription factors, which revealed
      unanticipated cellular diversity. Moreover, we identified a novel nephron
      subdomain marked by Wnt4 expression that we fate-mapped to the proximal mature
      nephron. Significant conservation was observed between human and mouse
      patterning. We also determined the time at which markers for mature nephron cell
      types first emerge-critical data for the renal organoid field. These findings
      have conceptual implications for the evolutionary processes driving the diversity
      of mammalian organ systems. Furthermore, these findings provide practical
      insights beyond those gained with mouse and rat models that will guide in vitro
      efforts to harness the developmental programs necessary to build human kidney
      structures.

PMID- 29449452
TI  - Evolution and Kidney Development: A Rosetta Stone for Nephrology.

PMID- 29449453
TI  - Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.
AB  - Human kidney function is underpinned by approximately 1,000,000 nephrons,
      although the number varies substantially, and low nephron number is linked to
      disease. Human kidney development initiates around 4 weeks of gestation and ends
      around 34-37 weeks of gestation. Over this period, a reiterative inductive
      process establishes the nephron complement. Studies have provided insightful
      anatomic descriptions of human kidney development, but the limited histologic
      views are not readily accessible to a broad audience. In this first paper in a
      series providing comprehensive insight into human kidney formation, we examined
      human kidney development in 135 anonymously donated human kidney specimens. We
      documented kidney development at a macroscopic and cellular level through
      histologic analysis, RNA in situ hybridization, immunofluorescence studies, and
      transcriptional profiling, contrasting human development (4-23 weeks) with mouse
      development at selected stages (embryonic day 15.5 and postnatal day 2). The high
      resolution histologic interactive atlas of human kidney organogenesis generated
      can be viewed at the GUDMAP database (www.gudmap.org) together with three
      dimensional reconstructions of key components of the data herein. At the anatomic
      level, human and mouse kidney development differ in timing, scale, and global
      features such as lobe formation and progenitor niche organization. The data also
      highlight differences in molecular and cellular features, including the
      expression and cellular distribution of anchor gene markers used to identify key
      cell types in mouse kidney studies. These data will facilitate and inform in
      vitro efforts to generate human kidney structures and comparative functional
      analyses across mammalian species.

PMID- 29449454
TI  - Deleting HDAC3 rescues long-term memory impairments induced by disruption of the
      neuron-specific chromatin remodeling subunit BAF53b.
AB  - Multiple epigenetic mechanisms, including histone acetylation and nucleosome
      remodeling, are known to be involved in long-term memory formation. Enhancing
      histone acetylation by deleting histone deacetylases, like HDAC3, typically
      enhances long-term memory formation. In contrast, disrupting nucleosome
      remodeling by blocking the neuron-specific chromatin remodeling subunit BAF53b
      impairs long-term memory. Here, we show that deleting HDAC3 can ameliorate the
      impairments in both long-term memory and synaptic plasticity caused by BAF53b
      mutation. This suggests a dynamic interplay exists between histone
      acetylation/deacetylation and nucleosome remodeling mechanisms in the regulation
      of memory formation.

PMID- 29449455
TI  - The beneficial effect of prior experience on the acquisition of spatial memory in
      rats with CA1, but not large hippocampal lesions: a possible role for schema
      formation.
AB  - Prior experience has been shown to improve learning in both humans and animals,
      but it is unclear what aspects of recent experience are necessary to produce
      beneficial effects. Here, we examined the capacity of rats with complete
      hippocampal lesions, restricted CA1 lesions, or sham surgeries to benefit from
      prior experience. Animals were tested in two different spatial tasks in the
      watermaze, the conventional watermaze task and delayed match-to-position. The two
      lesions impaired performance in both tasks when rats had no prior experience.
      However, when given prior training with one task, CA1 lesions had no effect on
      performance in the other task. In contrast, rats with hippocampal lesions did not
      benefit from prior training. The findings show that prior experience can benefit
      learning even when the previously learned task and a new task are quite
      different. The concept of schema may be useful for understanding the benefits of
      prior experience.

PMID- 29449456
TI  - Place learning overrides innate behaviors in Drosophila.
AB  - Animals in a natural environment confront many sensory cues. Some of these cues
      bias behavioral decisions independent of experience, and action selection can
      reveal a stimulus-response (S-R) connection. However, in a changing environment
      it would be a benefit for an animal to update behavioral action selection based
      on experience, and learning might modify even strong S-R relationships. How
      animals use learning to modify S-R relationships is a largely open question.
      Three sensory stimuli, air, light, and gravity sources were presented to
      individual Drosophila melanogaster in both naive and place conditioning
      situations. Flies were tested for a potential modification of the S-R
      relationships of anemotaxis, phototaxis, and negative gravitaxis by a contingency
      that associated place with high temperature. With two stimuli, significant S-R
      relationships were abandoned when the cue was in conflict with the place learning
      contingency. The role of the dunce (dnc) cAMP-phosphodiesterase and the rutabaga
      (rut) adenylyl cyclase were examined in all conditions. Both dnc1 and rut2080
      mutant flies failed to display significant S-R relationships with two attractive
      cues, and have characteristically lower conditioning scores under most
      conditions. Thus, learning can have profound effects on separate native S-R
      relationships in multiple contexts, and mutation of the dnc and rut genes reveal
      complex effects on behavior.

PMID- 29449459
TI  - How useful are simple clinical features and non-invasive imaging at predicting an
      underlying structural cause of acute intracerebral haemorrhage?

PMID- 29449458
TI  - A Barnes maze for juvenile rats delineates the emergence of spatial navigation
      ability.
AB  - The neural bases of cognition may be greatly informed by relating temporally
      defined developmental changes in behavior with concurrent alterations in neural
      function. A robust improvement in performance in spatial learning and memory
      tasks occurs at 3 wk of age in rodents. We reported that the developmental
      increase of spontaneous alternation in a Y-maze was related to changes in
      temporal dynamics of fast glutamatergic synaptic transmission in the hippocampus.
      We also showed that, during allothetic behaviors in the Y-maze, network
      oscillation power increased at frequency bands known to support spatial learning
      and memory in adults. However, there are no discrete learning and memory phases
      during free exploration in the Y-maze. Thus, we adapted the Barnes maze for use
      with juvenile rats. Following a single platform exposure in dim light on the day
      before training (to encourage exploration), animals were trained on the
      subsequent 2 d in bright light to find a hidden escape box and then underwent a
      memory test 24 h later. During escape training, the older animals learned the
      task in 1 d, while the younger animals required 2 d and did not reach the
      performance of older animals. Long-term memory performance was also superior in
      the older animals. Thus, we have validated the use of the Barnes maze for this
      developmental period and established a timeline for the ontogeny of spatial
      navigation ability in this maze around 3 wk of age. Subsequent work will pair in
      vivo recording of hippocampal oscillations and single units with this task to
      help identify how hippocampal maturation might relate to performance
      improvements.

PMID- 29449457
TI  - The activity of thalamic nucleus reuniens is critical for memory retrieval, but
      not essential for the early phase of "off-line" consolidation.
AB  - Spatial navigation depends on the hippocampal function, but also requires
      bidirectional interactions between the hippocampus (HPC) and the prefrontal
      cortex (PFC). The cross-regional communication is typically regulated by critical
      nodes of a distributed brain network. The thalamic nucleus reuniens (RE) is
      reciprocally connected to both HPC and PFC and may coordinate the information
      flow within the HPC-PFC pathway. Here we examined if RE activity contributes to
      the spatial memory consolidation. Rats were trained to find reward following a
      complex trajectory on a crossword-like maze. Immediately after each of the five
      daily learning sessions the RE was reversibly inactivated by local injection of
      muscimol. The post-training RE inactivation affected neither the spatial task
      acquisition nor the memory retention, which was tested after a 20-d "forgetting"
      period. In contrast, the RE inactivation in well-trained rats prior to the maze
      exposure impaired the task performance without affecting locomotion or appetitive
      motivation. Our results support the role of the RE in memory retrieval and/or
      "online" processing of spatial information, but do not provide evidence for its
      engagement in "off-line" processing, at least within a time window immediately
      following learning experience.

PMID- 29449460
TI  - PFN2 and GAMT as common molecular determinants of axonal Charcot-Marie-Tooth
      disease.
AB  - BACKGROUND: Charcot-Marie-Tooth type 2 (CMT2) neuropathy is characterised by a
      vast clinical and genetic heterogeneity complicating its diagnosis and
      therapeutic intervention. Identification of molecular signatures that are common
      to multiple CMT2 subtypes can aid in developing therapeutic strategies and
      measuring disease outcomes. METHODS: A proteomics-based approach was performed on
      lymphoblasts from CMT2 patients genetically diagnosed with different gene
      mutations to identify differentially regulated proteins. The candidate proteins
      were validated through real-time quantitative PCR and western blotting on
      lymphoblast samples of patients and controls, motor neurons differentiated from
      patient-derived induced pluripotent stem cells (iPSCs) and sciatic nerves of CMT2
      mouse models. RESULTS: Proteomic profiling of patient lymphoblasts resulted in
      the identification of profilin 2 (PFN2) and guanidinoacetate methyltransferase
      (GAMT) as commonly downregulated proteins in different genotypes compared with
      healthy controls. This decrease was also observed at the transcriptional level on
      screening 43 CMT2 patients and 22 controls, respectively. A progressive decrease
      in PFN2 expression with age was observed in patients, while in healthy controls
      its expression increased with age. Reduced PFN2 expression was also observed in
      motor neurons differentiated from CMT2 patient-derived iPSCs and sciatic nerves
      of CMT2 mice when compared with controls. However, no change in GAMT levels was
      observed in motor neurons and CMT2 mouse-derived sciatic nerves. CONCLUSIONS: We
      unveil PFN2 and GAMT as molecular determinants of CMT2 with possible indications
      of the role of PFN2 in the pathogenesis and disease progression. This is the
      first study describing biomarkers that can boost the development of therapeutic
      strategies targeting a wider spectrum of CMT2 patients.

PMID- 29449461
TI  - Neurointerventional surgery: enlightenment in the ischemic, but not the
      hemorrhagic, field.

PMID- 29449463
TI  - Comment on "Selective anaerobic oxidation of methane enables direct synthesis of
      methanol".
AB  - The comment and response concerning the report of oxidation of methane to
      methanol by water (Reports, 5 May 2017, p. 523) do not fully capture the
      implications of thermodynamic limitations. A nonisothermal process in which each
      cycle requires a large temperature swing and permits only substoichiometric
      methane conversion surely could not be carried out on any practical scale.

PMID- 29449462
TI  - Enantioselective C(sp3)-H bond activation by chiral transition metal catalysts.
AB  - Organic molecules are rich in carbon-hydrogen bonds; consequently, the
      transformation of C-H bonds to new functionalities (such as C-C, C-N, and C-O
      bonds) has garnered much attention by the synthetic chemistry community. The
      utility of C-H activation in organic synthesis, however, cannot be fully realized
      until chemists achieve stereocontrol in the modification of C-H bonds. This
      Review highlights recent efforts to enantioselectively functionalize C(sp3)-H
      bonds via transition metal catalysis, with an emphasis on key principles for both
      the development of chiral ligand scaffolds that can accelerate metalation of
      C(sp3)-H bonds and stereomodels for asymmetric metalation of prochiral C-H bonds
      by these catalysts.

PMID- 29449466
TI  - News at a glance.

PMID- 29449464
TI  - Response to Comment on "Selective anaerobic oxidation of methane enables direct
      synthesis of methanol".
AB  - Labinger argues that stepwise reaction of methane with water to produce methanol
      and hydrogen will never be commercially feasible because of its substoichiometric
      basis with respect to the active site and the requirement of a large temperature
      swing. This comment is not touching any new ground, beyond describing the
      thermodynamic feasibility, thermal cycling, and the role of water as discussed
      previously. Most important, it does not have a solid numerical basis.

PMID- 29449465
TI  - Exploration before exploitation.

PMID- 29449467
TI  - Science gets modest reprieve in Trump budget.

PMID- 29449468
TI  - A weight limit emerges for neutron stars.

PMID- 29449469
TI  - Artificial intelligence faces reproducibility crisis.

PMID- 29449470
TI  - U.K. moms are turning parenting into an experiment.

PMID- 29449471
TI  - 'CAMERA' records cell action with new CRISPR tricks.

PMID- 29449472
TI  - Isotope cloud linked to failed neutrino source.

PMID- 29449474
TI  - The carbon harvest.

PMID- 29449473
TI  - The data thugs.

PMID- 29449475
TI  - Is evolution predictable?

PMID- 29449476
TI  - Controlling learning and epilepsy together.

PMID- 29449477
TI  - The value of pollinator species diversity.

PMID- 29449478
TI  - Capsules made from prefabricated thin films.

PMID- 29449479
TI  - The changing face of urban air pollution.

PMID- 29449480
TI  - Chromatin regulation and immune escape.

PMID- 29449481
TI  - Was there ever really a "sugar conspiracy"?

PMID- 29449482
TI  - Salton Sea: Ecosystem in transition.

PMID- 29449483
TI  - Fund the Biological Survey Unit.

PMID- 29449484
TI  - As autonomous vehicles approach.

PMID- 29449485
TI  - Volatile chemical products emerging as largest petrochemical source of urban
      organic emissions.
AB  - A gap in emission inventories of urban volatile organic compound (VOC) sources,
      which contribute to regional ozone and aerosol burdens, has increased as
      transportation emissions in the United States and Europe have declined rapidly. A
      detailed mass balance demonstrates that the use of volatile chemical products
      (VCPs)-including pesticides, coatings, printing inks, adhesives, cleaning agents,
      and personal care products-now constitutes half of fossil fuel VOC emissions in
      industrialized cities. The high fraction of VCP emissions is consistent with
      observed urban outdoor and indoor air measurements. We show that human exposure
      to carbonaceous aerosols of fossil origin is transitioning away from
      transportation-related sources and toward VCPs. Existing U.S. regulations on VCPs
      emphasize mitigating ozone and air toxics, but they currently exempt many
      chemicals that lead to secondary organic aerosols.

PMID- 29449486
TI  - Natural selection and the predictability of evolution in Timema stick insects.
AB  - Predicting evolution remains difficult. We studied the evolution of cryptic body
      coloration and pattern in a stick insect using 25 years of field data,
      experiments, and genomics. We found that evolution is more difficult to predict
      when it involves a balance between multiple selective factors and uncertainty in
      environmental conditions than when it involves feedback loops that cause
      consistent back-and-forth fluctuations. Specifically, changes in color-morph
      frequencies are modestly predictable through time (r2 = 0.14) and driven by
      complex selective regimes and yearly fluctuations in climate. In contrast,
      temporal changes in pattern-morph frequencies are highly predictable due to
      negative frequency-dependent selection (r2 = 0.86). For both traits, however,
      natural selection drives evolution around a dynamic equilibrium, providing some
      predictability to the process.

PMID- 29449487
TI  - Wrapping with a splash: High-speed encapsulation with ultrathin sheets.
AB  - Many complex fluids rely on surfactants to contain, protect, or isolate liquid
      drops in an immiscible continuous phase. Thin elastic sheets can wrap liquid
      drops in a spontaneous process driven by capillary forces. For encapsulation by
      sheets to be practically viable, a rapid, continuous, and scalable process is
      essential. We exploit the fast dynamics of droplet impact to achieve wrapping of
      oil droplets by ultrathin polymer films in a water phase. Despite the violence of
      splashing events, the process robustly yields wrappings that are optimally shaped
      to maximize the enclosed fluid volume and have near-perfect seams. We achieve
      wrappings of targeted three-dimensional (3D) shapes by tailoring the 2D boundary
      of the films and show the generality of the technique by producing both oil-in
      water and water-in-oil wrappings.

PMID- 29449488
TI  - Natural noncanonical protein splicing yields products with diverse beta-amino
      acid residues.
AB  - Current textbook knowledge holds that the structural scope of ribosomal
      biosynthesis is based exclusively on alpha-amino acid backbone topology. Here we
      report the genome-guided discovery of bacterial pathways that posttranslationally
      create beta-amino acid-containing products. The transformation is widespread in
      bacteria and is catalyzed by an enzyme belonging to a previously uncharacterized
      radical S-adenosylmethionine family. We show that the beta-amino acids result
      from an unusual protein splicing process involving backbone carbon-carbon bond
      cleavage and net excision of tyramine. The reaction can be used to incorporate
      diverse and multiple beta-amino acids into genetically encoded precursors in
      Escherichia coli In addition to enlarging the set of basic amino acid components,
      the excision generates keto functions that are useful as orthogonal reaction
      sites for chemical diversification.

PMID- 29449489
TI  - Observation of three-photon bound states in a quantum nonlinear medium.
AB  - Bound states of massive particles, such as nuclei, atoms, or molecules,
      constitute the bulk of the visible world around us. By contrast, photons
      typically only interact weakly. We report the observation of traveling three
      photon bound states in a quantum nonlinear medium where the interactions between
      photons are mediated by atomic Rydberg states. Photon correlation and conditional
      phase measurements reveal the distinct bunching and phase features associated
      with three-photon and two-photon bound states. Such photonic trimers and dimers
      possess shape-preserving wave functions that depend on the constituent photon
      number. The observed bunching and strongly nonlinear optical phase are described
      by an effective field theory of Rydberg-induced photon-photon interactions. These
      observations demonstrate the ability to realize and control strongly interacting
      quantum many-body states of light.

PMID- 29449490
TI  - Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial
      memory.
AB  - Temporal lobe epilepsy (TLE) is characterized by debilitating, recurring seizures
      and an increased risk for cognitive deficits. Mossy cells (MCs) are key neurons
      in the hippocampal excitatory circuit, and the partial loss of MCs is a major
      hallmark of TLE. We investigated how MCs contribute to spontaneous ictal activity
      and to spatial contextual memory in a mouse model of TLE with hippocampal
      sclerosis, using a combination of optogenetic, electrophysiological, and
      behavioral approaches. In chronically epileptic mice, real-time optogenetic
      modulation of MCs during spontaneous hippocampal seizures controlled the
      progression of activity from an electrographic to convulsive seizure. Decreased
      MC activity is sufficient to impede encoding of spatial context, recapitulating
      observed cognitive deficits in chronically epileptic mice.

PMID- 29449491
TI  - Species turnover promotes the importance of bee diversity for crop pollination at
      regional scales.
AB  - Ecologists have shown through hundreds of experiments that ecological communities
      with more species produce higher levels of essential ecosystem functions such as
      biomass production, nutrient cycling, and pollination, but whether this finding
      holds in nature (that is, in large-scale and unmanipulated systems) is
      controversial. This knowledge gap is troubling because ecosystem services have
      been widely adopted as a justification for global biodiversity conservation. Here
      we show that, to provide crop pollination in natural systems, the number of bee
      species must increase by at least one order of magnitude compared with that in
      field experiments. This increase is driven by species turnover and its
      interaction with functional dominance, mechanisms that emerge only at large
      scales. Our results show that maintaining ecosystem services in nature requires
      many species, including relatively rare ones.

PMID- 29449492
TI  - Structures of C1-IgG1 provide insights into how danger pattern recognition
      activates complement.
AB  - Danger patterns on microbes or damaged host cells bind and activate C1, inducing
      innate immune responses and clearance through the complement cascade. How these
      patterns trigger complement initiation remains elusive. Here, we present cryo
      electron microscopy analyses of C1 bound to monoclonal antibodies in which we
      observed heterogeneous structures of single and clustered C1-immunoglobulin G1
      (IgG1) hexamer complexes. Distinct C1q binding sites are observed on the two Fc
      CH2 domains of each IgG molecule. These are consistent with known interactions
      and also reveal additional interactions, which are supported by functional IgG1
      mutant analysis. Upon antibody binding, the C1q arms condense, inducing
      rearrangements of the C1r2s2 proteases and tilting C1q's cone-shaped stalk. The
      data suggest that C1r may activate C1s within single, strained C1 complexes or
      between neighboring C1 complexes on surfaces.

PMID- 29449494
TI  - Got milk, must conference.

PMID- 29449493
TI  - Lipopolysaccharide is transported to the cell surface by a membrane-to-membrane
      protein bridge.
AB  - Gram-negative bacteria have an outer membrane that serves as a barrier to noxious
      agents in the environment. This protective function is dependent on
      lipopolysaccharide, a large glycolipid located in the outer leaflet of the outer
      membrane. Lipopolysaccharide is synthesized at the cytoplasmic membrane and must
      be transported to the cell surface. To understand this transport process, we
      reconstituted membrane-to-membrane movement of lipopolysaccharide by
      incorporating purified inner and outer membrane transport complexes into separate
      proteoliposomes. Transport involved stable association between the inner and
      outer membrane proteoliposomes. Our results support a model in which
      lipopolysaccharide molecules are pushed one after the other in a PEZ dispenser
      like manner across a protein bridge that connects the inner and outer membranes.

PMID- 29449495
TI  - Evaluation of Self-reported Patient Experiences: Insights from Digital Patient
      Communities in Psoriatic Arthritis.
AB  - OBJECTIVE: To evaluate the types of experiences and treatment access challenges
      of patients with psoriatic arthritis (PsA) using self-reported online narratives.
      METHODS: English-language patient narratives reported between January 2010 and
      May 2016 were collected from 31 online sources (general health social networking
      sites, disease-focused patient forums, treatment reviews, general health forums,
      mainstream social media sites) for analysis of functional impairment and 40
      online sources for assessment of barriers to treatment. Using natural language
      processing and manual curation, patient-reported experiences were categorized
      into 6 high-level concepts of functional impairment [social, physical, emotional,
      cognitive, role activity (SPEC-R), and general] and 6 categories to determine
      barriers to treatment access (coverage ineligibility, out-of-pocket cost, issues
      with assistance programs, clinical ineligibility, formulary placement/sequence,
      doctor guidance). The SPEC-R categorization was also applied to 3 validated PsA
      patient-reported outcome (PRO) instruments to evaluate their capacity to collect
      lower-level subconcepts extracted from patient narratives. RESULTS: Of 15,390
      narratives collected from 3139 patients with PsA for exploratory analysis,
      physical concepts were the most common (81.5%), followed by emotional (50.7%),
      cognitive (20.0%), role activity (8.1%), and social (5.6%) concepts. Cognitive
      impairments and disease burden on family and parenting were not recorded by PsA
      PRO instruments. The most commonly cited barriers to treatment were coverage
      ineligibility (51.6%) and high out-of-pocket expenses (31.7%). CONCLUSION:
      Patients often discussed physical and emotional implications of PsA in online
      platforms; some commonly used PRO instruments in PsA may not identify cognitive
      issues or parenting/family burden. Nearly one-third of patients with PsA reported
      access barriers to treatment.

PMID- 29449496
TI  - Patient-reported Outcomes, Resource Use, and Social Participation of Patients
      with Rheumatoid Arthritis Treated with Biologics in Alberta: Experience of
      Indigenous and Non-indigenous Patients.
AB  - OBJECTIVE: To characterize patient-reported outcomes, resource use, and social
      participation during the course of biologic therapy for indigenous and non
      indigenous patients with rheumatoid arthritis (RA). METHODS: Patients initiating
      biologic therapy (2004 to 2012) were characterized longitudinally for patient
      reported outcomes including physical function measured by the Health Assessment
      Questionnaire, EQ-5D, well-being [Medical Outcomes Study Short Form-36 (SF-36)],
      and visual analog scales for pain, fatigue, sleep, stiffness, and patient's
      global assessment. Resource use, participation in activities of daily living, and
      effect of RA on work productivity were also evaluated for change during therapy.
      RESULTS: Indigenous patients (n = 90) presented with significantly worse scores
      for global evaluation, pain, sleep, quality of life, well-being, and physical
      function compared to non-indigenous patients (n = 1400). All patient-reported
      outcomes improved significantly during treatment for patients in both groups, but
      pain, sleep, and SF-36 physical health score changes occurred at slower rates for
      indigenous patients [difference in slopes 0.09 (p = 0.029), 0.08 (p = 0.043), and
      -0.35 (p = 0.03), respectively]. Performance of daily activities was affected for
      50% of indigenous compared to 37% of non-indigenous patients, with more use of
      community services and assistance from others. Employed indigenous patients
      reported twice the number of days being unable to work owing to RA compared to
      employed non-indigenous patients. Of the unemployed indigenous patients, 82%
      indicated they had stopped working because of arthritis, versus 48% of non
      indigenous patients (p < 0.0001). CONCLUSIONS: Indigenous patients have greater
      consequences of RA regarding experienced symptoms, health-related quality of
      life, disruption of performance of activities of daily living, and reduced
      employment participation.

PMID- 29449497
TI  - Rheumatologists' Views and Experiences in Managing Rheumatoid Arthritis in
      Elderly Patients: A Qualitative Study.
AB  - OBJECTIVE: In this qualitative study we analyzed the (1) influence of age,
      comorbidity, and frailty on management goals in elderly patients with RA; (2)
      experiences of rheumatologists regarding the use of the Disease Activity Score at
      28 joints (DAS28) to monitor disease activity; and (3) differences in management
      strategies in elderly patients with RA compared to their younger counterparts.
      METHODS: Rheumatologists were purposively sampled for a semistructured interview.
      Two readers independently read and coded the interview transcripts. Important
      concepts were taxonomically categorized and combined in overarching themes by
      using NVivo 11 software. RESULTS: Seventeen rheumatologists (mean age 44.8 yrs,
      SD 7.7 yrs; 29% male) from 9 medical centers were interviewed. Preserving an
      acceptable level of functioning was the most important management goal in
      patients >= 80 years and in patients with high levels of comorbidity and frailty.
      The DAS28 score less frequently steered the management strategy, because
      rheumatologists commented that comorbidity and an age-related erythrocyte
      sedimentation rate elevation might distort the DAS28 score. Instead, management
      of elderly patients highly depended on comorbidity, frailty, and their subsequent
      effects such as cognitive and physical decline, dependency, and polypharmacy.
      Presence of 1 or more of these factors frequently resulted in a less future
      oriented management approach with less emphasis on the maximal prevention of
      joint erosions. CONCLUSION: The treat-to-target model is not automatically
      adopted in the elderly patient population. Future evidence-based RA management
      recommendations for elderly patients with RA are needed and should account for
      factors such as comorbidity and frailty.

PMID- 29449498
TI  - Early Psoriatic Arthritis Versus Early Seronegative Rheumatoid Arthritis: Role of
      Dermoscopy Combined with Ultrasonography for Differential Diagnosis.
AB  - OBJECTIVE: Exclusion of psoriatic skin/nail lesions is important in
      differentiating early seronegative rheumatoid arthritis (ERA) from early
      polyarticular psoriatic arthritis (EPsA) and such manifestations may go unnoticed
      in atypical or minimally expressed cases. The aim of this study is to assess the
      usefulness of integrated rheumatological-dermatological evaluation in
      highlighting dermatological lesions missed on rheumatological examination and to
      investigate the role of ultrasonography (US) and dermoscopy in improving the
      recognition of subclinical psoriatic findings. METHODS: Patients with a new
      diagnosis of seropositive or seronegative ERA and EPsA with prevalent hands
      involvement were recruited. All were reassessed for the presence of psoriatic
      lesions during an integrated rheumatological-dermatological clinical evaluation
      and underwent hands US and proximal nailfold dermoscopy. RESULTS: Seventy-three
      consecutive subjects were included in the study: 25 with seropositive ERA, 23
      with seronegative ERA, and 25 with EPsA. One-fourth of the subjects initially
      diagnosed as seronegative ERA presented cutaneous or nail psoriasis on integrated
      rheumatological-dermatological evaluation, thereby being reclassified as EPsA.
      The presence of at least 1 extrasynovial feature on hand US and dotted vessels on
      proximal nailfold dermoscopy was significantly associated with EPsA, with a
      sensitivity of 68.0% and 96.0% and a specificity of 88.1% and 83.3% for US and
      dermoscopy, respectively. When used together, specificity for PsA diagnosis
      raised to 90.5%. CONCLUSION: Integrated rheumatological-dermatological clinical
      evaluation may be helpful in identifying patients with EPsA misclassified as
      seronegative ERA. Additionally, US and dermoscopy may be used as supportive tools
      in identifying subclinical psoriatic features, which may come in handy in
      distinguishing EPsA from ERA.

PMID- 29449499
TI  - Clinical Correlates, Outcomes, and Predictors of Inflammatory Ocular Disease
      Associated with Rheumatoid Arthritis in the Biologic Era.
AB  - OBJECTIVE: Inflammatory ocular disease (IOD) is a rare but severe extraarticular
      manifestation of rheumatoid arthritis (ExRA) with high mortality. The aim of our
      study was to examine clinical characteristics of IOD in rheumatoid arthritis (RA)
      and their effect on disease severity and outcomes in recent years. METHODS: A
      retrospective cohort of RA patients with IOD evaluated between 1996 and 2013 was
      assembled and compared to RA comparators without IOD and matched for age, sex,
      and disease duration. RESULTS: We identified 92 patients (69% female; mean age 62
      yrs) with IOD: 33 scleritis, 23 episcleritis, 21 peripheral ulcerative keratitis
      (PUK), 14 uveitis, and 1 with orbital inflammation. The majority of patients with
      scleritis, episcleritis, and PUK was seropositive versus uveitis (> 80% vs 62%, p
      = 0.048). PUK and scleritis were more symptomatic compared to episcleritis and
      uveitis, and often required systemic therapy. Time to resolution was longer in
      scleritis than episcleritis (p = 0.01). PUK, scleritis, and uveitis had severe
      ocular sequelae. Prevalence of severe ExRA (18% vs 4%, p = 0.004) and dry eye
      syndrome (42% vs 26%, p = 0.024) was higher among patients with IOD than
      comparators. The incidence of new ExRA over 5-year followup was also higher among
      cases (29% vs 11%, p = 0.022). Ten-year survival was similar among RA patients
      with and without IOD (66% vs 64%, p = 0.56), with no differences noted among IOD
      subtypes. CONCLUSION: This large single-center study highlights the variable
      presentation and outcomes of IOD in RA. Although ocular complications are
      associated with significant morbidity, it is reassuring that survival among those
      with IOD is now similar to those without ocular disease.

PMID- 29449500
TI  - The Cost-effectiveness of Biannual Serum Urate (SU) Monitoring after Reaching
      Target in Gout: A Health Economic Analysis Comparing SU Monitoring.
AB  - OBJECTIVE: The 2012 American College of Rheumatology gout management guidelines
      recommend monitoring serum urate (SU) every 6 months after target SU has been
      achieved. Our objective was to determine through modeling whether this testing
      would be cost-effective, considering financial cost, quality of life, and
      estimated change in adherence. METHODS: A cost-utility analysis was completed
      with a 3-arm model: (1) no regular urate monitoring; (2) annual urate monitoring;
      and (3) biannual urate monitoring. Inputs to the model for health-related quality
      of life, flare rate, and treatment location were drawn from the medical
      literature and modeled over a lifetime horizon. RESULTS: No monitoring was the
      least costly (Australian$6974) but least effective [13.51 quality-adjusted life
      yrs (QALY)], while annual urate monitoring [A$7117; 13.53 QALY; incremental cost
      effectiveness ratio (ICER) A$13,678/QALY gained] and biannual monitoring [A$7298;
      13.54 QALY; ICER A$15,420 per QALY gained] were both cost-effective alternatives
      in base case analysis. Sensitivity analysis on both an individual component level
      and a probabilistic sensitivity analysis (PSA) demonstrated that the result was
      robust to changes in input variables. An improvement in adherence of >= 3.5% with
      biannual monitoring was all that was required to demonstrate cost-effectiveness.
      In PSA, the probability of biannual monitoring was 78%, no monitoring was 20%,
      and annual monitoring was 2%. CONCLUSION: The results suggest that biannual SU
      monitoring after attaining target SU is the most cost-effective, compared with no
      testing and annual testing.

PMID- 29449501
TI  - Diffusion-weighted Imaging Is a Sensitive and Specific Magnetic Resonance
      Sequence in the Diagnosis of Ankylosing Spondylitis.
AB  - OBJECTIVE: We tested the discriminatory capacity of diffusion-weighted magnetic
      resonance imaging (DWI) and its potential as an objective measure of treatment
      response to tumor necrosis factor inhibition in ankylosing spondylitis (AS).
      METHODS: Three cohorts were studied prospectively: (1) 18 AS patients with Bath
      Ankylosing Spondylitis Disease Activity Index > 4, and erythrocyte sedimentation
      rate > 25 and/or C-reactive protein > 10 meeting the modified New York criteria
      for AS; (2) 20 cases of nonradiographic axial spondyloarthritis (nr-axSpA) as
      defined by the Assessment of Spondyloarthritis international Society (ASAS)
      criteria; and (3) 20 non-AS patients with chronic low back pain, aged between 18
      and 45 years, who did not meet the imaging arm of the ASAS criteria for axSpA.
      Group 1 patients were studied prior to and following adalimumab treatment.
      Patients were assessed by DWI and conventional magnetic resonance imaging (MRI),
      and standard nonimaging measures. RESULTS: At baseline, in contrast to standard
      nonimaging measures, DWI apparent diffusion coefficient (ADC) values showed good
      discriminatory performance [area under the curve (AUC) > 80% for Group 1 or 2
      compared with Group 3]. DWI ADC values were significantly lower posttreatment
      (0.45 +/- 0.433 before, 0.154 +/- 0.23 after, p = 0.0017), but had modest
      discriminating capacity comparing pre- and posttreatment measures (AUC = 68%).
      This performance was similar to the manual Spondyloarthritis Research Consortium
      of Canada (SPARCC) scoring system. CONCLUSION: DWI is informative for diagnosis
      of AS and nr-axSpA, and has moderate utility in assessment of disease activity or
      treatment response, with performance similar to that of the SPARCC MRI score.

PMID- 29449502
TI  - The Crescentic Implication of Renal Outcomes in Proliferative Lupus Nephritis.
AB  - OBJECTIVE: To determine the association between crescents and renal outcomes, and
      the implications on therapeutic choices. METHODS: There were 231 patients with
      biopsy-proven proliferative lupus nephritis (PLN) who were divided into 4 groups:
      59 patients were in the noncrescent group (NC); 59 patients exclusively with
      segmental crescents were in the segmental crescent group (SC); patients with
      circumferential crescents were categorized into 2 groups according to the
      crescentic ratio (C1 had 64 patients with <= 25%, and C2 had 49 patients with >
      25%). Their baseline laboratory tests, histopathological manifestations, and
      outcomes were compared. RESULTS: Remission rates in NC, SC, C1, and C2 groups
      were 92.1%, 85.4%, 95.0%, and 76.1%, respectively. Fewer patients in the C2 group
      achieved complete remission than the other 3 groups. For longterm outcomes
      evaluated by serum creatinine (SCr) doubling or endstage renal disease (ESRD),
      the renal survival rate was lowest in the C2 group (p = 0.003). Including
      clinical and pathological variables in the Cox proportional hazard regression
      model separately, the multivariate analysis revealed that these were independent
      risk factors for SCr doubling or ESRD: baseline SCr (with every 1 mg/dl increase:
      HR = 1.834, 95% CI 1.465-2.296; p < 0.001), hemoglobin (with every 1 g/l
      increase: HR = 0.970, 95% CI 0.947-0.992; p = 0.009), the proportions of cellular
      crescents (with every 1% increase: HR = 1.040, 95% CI 1.015-1.066; p = 0.002) and
      fibrocellular crescents (with every 1% increase: HR = 1.085, 95% CI 1.013-1.163;
      p = 0.020), and severe renal tubular atrophy (HR = 5.348, 95% CI 1.278-22.373; p
      = 0.022). CONCLUSION: PLN with crescents > 25% had worse renal outcomes both in
      short and long terms. Proportions of cellular and fibrocellular crescents were
      independent risk factors for poor renal survival.

PMID- 29449503
TI  - Early Renin-angiotensin System Blockade Improved Short-term and Longterm Renal
      Outcomes in Systemic Lupus Erythematosus Patients with Antiphospholipid
      associated Nephropathy.
AB  - OBJECTIVE: To investigate the renal protective effects of early renin-angiotensin
      aldosterone system (RAAS) blockade with renin-angiotensin system inhibitors
      (RASI) in systemic lupus erythematosus (SLE) patients with antiphospholipid
      associated nephropathy (aPLN). METHODS: Medical data of 57 SLE patients with
      biopsy-proven aPLN were analyzed. Early RAAS blockade was defined as
      administration of RASI within 3 months after kidney biopsy and continued for >=
      12 months. RESULTS: There was no significant difference in demographic data,
      laboratory findings, and renal histology by the time of kidney biopsy, except
      that the RASI group had higher proteinuria levels vs the non-RASI group [5.2 (2.8
      8.8) vs 1.9 (0.6-2.8) g/d, p = 0.005, respectively] and higher prevalence of
      hypertension (75% vs 29%, p = 0.001, respectively). No significant difference
      between the 2 groups was observed in estimated glomerular filtration rate (eGFR),
      mean arterial pressure, and proteinuria level at 12 months after kidney biopsy.
      The improvement ratio of eGFR at 12 months was significantly higher in the RASI
      group versus the non-RASI group [26% (-5 to 86) vs -2% (-20 to 20), p = 0.028,
      respectively], and the rate of change in eGFR beyond 12 months was similar
      between the 2 groups. During a mean followup of 80 months, 4 (23%) patients in
      the non-RASI group and 3 (8%) patients in the RASI group developed kidney disease
      progression. Early RAAS blockade significantly decreased the risk of kidney
      disease progression [HR = 0.11 (0.02-0.59); p = 0.010]. Proteinuria and
      hypertension controls were similar between the 2 groups. CONCLUSION: Early RAAS
      blockade improved the short-term and longterm renal outcomes in SLE patients with
      aPLN. The renal protective effect of RASI was independent of its antihypertensive
      and antiproteinuric effects.

PMID- 29449505
TI  - Detection of Crohn Disease in Patients with Spondyloarthropathy: The SpACE
      Capsule Study.
AB  - OBJECTIVE: Inflammatory bowel disease (IBD) is generally reported to be
      associated with spondylarthropathies (SpA) in 5%-15% of cases. Systematic
      colonoscopic assessment by protocol demonstrated mucosal inflammation
      characteristic of Crohn disease (CD) in up to one-third of patients with SpA.
      Video capsule endoscopy (CE) is a superior diagnostic tool to detect small bowel
      mucosal disease. Our study compared the accuracy of CE to standard colonoscopy
      for detection of inflammatory bowel lesions in patients with SpA, and to describe
      predictors of small bowel inflammation (SBI) in this cohort. METHODS: Prospective
      cross-sectional study of adult patients followed for SpA. Patients were evaluated
      by CE and standard colonoscopy with biopsies. SBI was quantified using the Lewis
      Score. Additional screening tests included fecal calprotectin (FCP), C-reactive
      protein (CRP), and a diagnostic panel of serologic, inflammatory and genetic
      tests (SGI). RESULTS: There were 64 patients recruited (53% female, mean age 42
      +/- 13 yrs). Chronic gastrointestinal (GI) symptoms were present in 57%. CE
      revealed significant SBI in 27/64 (42.2%), compared to 7/64 (10.9%) by standard
      colonoscopy (p = 0.035). Elevated FCP was associated with small bowel CD (OR 4.5,
      95% CI 1.01-19.9; p = 0.042). No correlation was observed with presence of GI
      symptoms, CRP, or SGI results. Finding CD led to a change in management in 65.2%
      of cases. CONCLUSION: CE uncovered SBI consistent with CD in 42.2% of patients
      with SpA, with a significant incremental yield over colonoscopy of 31%. FCP
      levels were significantly correlated with CE results, while GI symptoms and SGI
      results were poor predictors of SBI.

PMID- 29449504
TI  - Response to Tumor Necrosis Factor Inhibition in Male and Female Patients with
      Ankylosing Spondylitis: Data from a Swiss Cohort.
AB  - OBJECTIVE: To investigate sex differences in connection with the effectiveness of
      tumor necrosis factor inhibitors (TNFi) in patients with ankylosing spondylitis
      (AS). METHODS: A total of 440 patients with AS (294 men; 146 women) initiating a
      first TNFi in the prospective Swiss Clinical Quality Management Cohort were
      included. We evaluated the proportion of patients achieving the 20% and 40%
      improvement in the Assessment of Spondyloarthritis international Society criteria
      (ASAS20 and ASAS40) as well as Ankylosing Spondylitis Disease Activity Score
      (ASDAS) improvement and status scores at 1 year. Patients having discontinued
      TNFi were considered nonresponders. Logistic regression analyses were performed
      to adjust for important predictors of response. RESULTS: Compared to men, female
      patients had lower mean C-reactive protein levels, better spinal mobility, and
      more peripheral disease at the start. There was no sex disparity with regard to
      the ASDAS, the Bath Ankylosing Spondylitis Disease Activity and Functional
      indices, and the quality of life. At 1 year, 52% of women and 63% of men achieved
      an ASAS20 response (OR 0.63, 95% CI 0.37-1.07, p = 0.09). An inactive disease
      status (ASDAS < 1.3) was reached by 18% of women and 26% of men (OR 0.65, 95% CI
      0.32-1.27, p = 0.22). These sex differences in response to TNFi were more
      pronounced in adjusted analyses (OR 0.34, 95% CI 0.16-0.71, p = 0.005 for ASAS20
      and OR 0.10, 95% CI 0.03-0.31, p < 0.001 for ASDAS < 1.3) and confirmed for all
      the other outcomes assessed. CONCLUSION: In AS, fewer women respond to TNFi and
      women show a reduced response in comparison to men.

PMID- 29449506
TI  - Whole-body Magnetic Resonance Imaging in Axial Spondyloarthritis: Reduction of
      Sacroiliac, Spinal, and Entheseal Inflammation in a Placebo-controlled Trial of
      Adalimumab.
AB  - OBJECTIVE: To investigate whether adalimumab (ADA) reduces whole-body (WB-)
      magnetic resonance imaging (MRI) indices for inflammation in the entheses,
      peripheral joints, sacroiliac joints, spine, and the entire body in patients with
      axial spondyloarthritis (axSpA). METHODS: An investigator-initiated, randomized,
      placebo-controlled, double-blinded 48-week followup trial included 49 patients
      with axSpA, who had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
      >= 4.0 despite treatment with nonsteroidal antiinflammatory drugs and a clinical
      indication for tumor necrosis factor inhibitor treatment. Patients were
      randomized to subcutaneous ADA 40 mg or placebo every other week for 6 weeks;
      thereafter, all patients received ADA. Conventional MRI and WBMRI were performed
      at weeks 0, 6, 24, and 48. The primary WBMRI endpoint was the proportion of
      patients with an improvement in WBMRI total inflammation index above the smallest
      detectable change (SDC) at Week 6. RESULTS: The primary WBMRI endpoint
      (improvement of SDC > 2.3) was met in 11 (44%) patients in the ADA group and 3
      (13%) patients in the placebo group (p = 0.025, Fisher's exact test). The primary
      conventional MRI endpoint, the minimally important change in Spondyloarthritis
      Research Consortium of Canada Spine MRI Inflammation Index at Week 6, was
      achieved by 9 (36%) patients in the ADA group and 4 (17%) patients in the placebo
      group (p = 0.20). The primary clinical endpoint, BASDAI reduction > 50% or 2.0 at
      Week 24, was attained by 32 (65%) patients. CONCLUSION: ADA provided significant
      reductions in WBMRI indices of peripheral, axial, and whole-body inflammation in
      patients with axSpA. WBMRI is promising for objective assessment and monitoring
      of peripheral and axial disease activity in future clinical trials.

PMID- 29449507
TI  - Rewritable multi-event analog recording in bacterial and mammalian cells.
AB  - We present two CRISPR-mediated analog multi-event recording apparatus (CAMERA)
      systems that use base editors and Cas9 nucleases to record cellular events in
      bacteria and mammalian cells. The devices record signal amplitude or duration as
      changes in the ratio of mutually exclusive DNA sequences (CAMERA 1) or as single
      base modifications (CAMERA 2). We achieved recording of multiple stimuli in
      bacteria or mammalian cells, including exposure to antibiotics, nutrients,
      viruses, light, and changes in Wnt signaling. When recording to multicopy
      plasmids, reliable readout requires as few as 10 to 100 cells. The order of
      stimuli can be recorded through an overlapping guide RNA design, and memories can
      be erased and re-recorded over multiple cycles. CAMERA systems serve as "cell
      data recorders" that write a history of endogenous or exogenous signaling events
      into permanent DNA sequence modifications in living cells.

PMID- 29449509
TI  - Predicting reaction performance in C-N cross-coupling using machine learning.
AB  - Machine learning methods are becoming integral to scientific inquiry in numerous
      disciplines. We demonstrated that machine learning can be used to predict the
      performance of a synthetic reaction in multidimensional chemical space using data
      obtained via high-throughput experimentation. We created scripts to compute and
      extract atomic, molecular, and vibrational descriptors for the components of a
      palladium-catalyzed Buchwald-Hartwig cross-coupling of aryl halides with 4
      methylaniline in the presence of various potentially inhibitory additives. Using
      these descriptors as inputs and reaction yield as output, we showed that a random
      forest algorithm provides significantly improved predictive performance over
      linear regression analysis. The random forest model was also successfully applied
      to sparse training sets and out-of-sample prediction, suggesting its value in
      facilitating adoption of synthetic methodology.

PMID- 29449508
TI  - Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and
      Csm6.
AB  - Rapid detection of nucleic acids is integral for clinical diagnostics and
      biotechnological applications. We recently developed a platform termed SHERLOCK
      (specific high-sensitivity enzymatic reporter unlocking) that combines isothermal
      preamplification with Cas13 to detect single molecules of RNA or DNA. Through
      characterization of CRISPR enzymology and application development, we report here
      four advances integrated into SHERLOCK version 2 (SHERLOCKv2) (i) four-channel
      single-reaction multiplexing with orthogonal CRISPR enzymes; (ii) quantitative
      measurement of input as low as 2 attomolar; (iii) 3.5-fold increase in signal
      sensitivity by combining Cas13 with Csm6, an auxiliary CRISPR-associated enzyme;
      and (iv) lateral-flow readout. SHERLOCKv2 can detect Dengue or Zika virus single
      stranded RNA as well as mutations in patient liquid biopsy samples via lateral
      flow, highlighting its potential as a multiplexable, portable, rapid, and
      quantitative detection platform of nucleic acids.

PMID- 29449510
TI  - Winter color polymorphisms identify global hot spots for evolutionary rescue from
      climate change.
AB  - Maintenance of biodiversity in a rapidly changing climate will depend on the
      efficacy of evolutionary rescue, whereby population declines due to abrupt
      environmental change are reversed by shifts in genetically driven adaptive
      traits. However, a lack of traits known to be under direct selection by
      anthropogenic climate change has limited the incorporation of evolutionary
      processes into global conservation efforts. In 21 vertebrate species, some
      individuals undergo a seasonal color molt from summer brown to winter white as
      camouflage against snow, whereas other individuals remain brown. Seasonal snow
      duration is decreasing globally, and fitness is lower for winter white animals on
      snowless backgrounds. Based on 2713 georeferenced samples of known winter coat
      color-from eight species across trophic levels-we identify environmentally driven
      clinal gradients in winter coat color, including polymorphic zones where winter
      brown and white morphs co-occur. These polymorphic zones, underrepresented by
      existing global protected area networks, indicate hot spots for evolutionary
      rescue in a changing climate.

PMID- 29449511
TI  - CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase
      activity.
AB  - CRISPR-Cas12a (Cpf1) proteins are RNA-guided enzymes that bind and cut DNA as
      components of bacterial adaptive immune systems. Like CRISPR-Cas9, Cas12a has
      been harnessed for genome editing on the basis of its ability to generate
      targeted, double-stranded DNA breaks. Here we show that RNA-guided DNA binding
      unleashes indiscriminate single-stranded DNA (ssDNA) cleavage activity by Cas12a
      that completely degrades ssDNA molecules. We find that target-activated,
      nonspecific single-stranded deoxyribonuclease (ssDNase) cleavage is also a
      property of other type V CRISPR-Cas12 enzymes. By combining Cas12a ssDNase
      activation with isothermal amplification, we create a method termed DNA
      endonuclease-targeted CRISPR trans reporter (DETECTR), which achieves attomolar
      sensitivity for DNA detection. DETECTR enables rapid and specific detection of
      human papillomavirus in patient samples, thereby providing a simple platform for
      molecular diagnostics.

PMID- 29449512
TI  - Outcomes of Advanced Gastric Cancer Patients Treated with at Least Three Lines of
      Systemic Chemotherapy.

PMID- 29449513
TI  - Adolescents and Young Adults With a "Rare" Cancer: Getting Past Semantics to
      Optimal Care for Patients With Germ Cell Tumors.

PMID- 29449514
TI  - [Surgical Anatomy and Principal Techniques for the Endoscopic Hematoma
      Evacuation].

PMID- 29449515
TI  - [Therapeutic Effects of Low-Dose Bevacizumab for the Treatment of Recurrent Brain
      Metastases].
AB  - OBJECTIVE: Molecularly targeted therapy has been adopted to treat a number of
      cancers. Bevacizumab, a recombinant humanized monoclonal antibody against
      vascular endothelial growth factor, is a representative agent used in molecularly
      targeted therapeutic regimens. However, the therapeutic effect of bevacizumab for
      the treatment of brain metastases remains unknown. We report the clinical effects
      of low dose bevacizumab(<=2.5mg/kg/week)to treat recurrent brain metastases.
      METHODS: We retrospectively analyzed patients with brain metastases who had been
      treated with bevacizumab between 2012 and 2016 at our institution. We identified
      clinical characteristics, including age, gender, primary tumor site, dose of
      bevacizumab, therapeutic and adverse effects, and magnetic resonance imaging
      results. The lesions were assessed with the RECIST criteria based on gadolinium
      enhanced T1-weighted, T2-weighted, and FLAIR images. Statistical analysis was
      performed using t-test and Fisher's exact test. RESULTS: The cohort comprised 26
      patients(8 men, 18 women)with a median age of 61 years(range 39-82 years). There
      were no significant clinical differences between the low dose and non-low dose
      groups. Patients in the low dose group did not report any adverse effects from
      bevacizumab. Three patients with brain metastases from colon cancer are
      illustrated to report the clinical course of low dose bevacizumab. CONCLUSION:
      Low dose bevacizumab may be a safe and effective therapeutic option to treat
      recurrent brain metastases from bevacizumab-sensitive cancers.

PMID- 29449516
TI  - [A Case of a Ruptured Cerebral Aneurysm Associated with Microscopic
      Polyangiitis].
AB  - CASE: A 71-year-old woman was receiving dialysis for microscopic
      polyangiitis(MPA). She was transported to the emergency room after developing a
      headache and losing consciousness. She was in a coma and had dense left
      paralysis. Head computed tomography(CT)showed a subarachnoid hemorrhage. Head
      three-dimensional CT angiography showed an aneurysm proximal to the right
      M2(inferior trunk), which was considered as the source of bleeding. We performed
      an emergency aneurysm clipping surgery. However, we placed a permanent clip on
      the arterial wall defect when the clip detached from the parent artery.
      Pathological examination of the aneurysm revealed that the layered structure of
      the artery was damaged because of fibrin degeneration, suggesting that the
      aneurysm was caused by vasculitis. Coma persisted after surgery, and the patient
      was transferred to another hospital. DISCUSSION: We found only one report
      demonstrating an association between a cerebral aneurysm and MPA. Aneurysms
      resulting from vasculitis are common at the periphery, rather than at vessel
      bifurcations. Cyclic inflammatory activity causes progressive destruction of the
      blood vessel wall, further expanding the lumen and forming an aneurysm.
      Therefore, such aneurysms are more fragile than true aneurysms, and are more
      likely to be damaged or detached during surgery, as in the present case. Trapping
      of the parent artery should be considered when the aneurysm is damaged or
      detached. Accordingly, preoperative planning could anticipate the need for
      superficial temporal artery to middle cerebral artery bypass.

PMID- 29449517
TI  - [A Case of Moyamoya Disease with Postoperative Cerebral Hyperperfusion Syndrome
      Followed by Cerebral Infarction due to Watershed Shift].
AB  - The concept of "watershed shift"(WS)has been proposed as a cause of the ischemic
      complications following a superficial temporal artery-middle cerebral artery(STA
      MCA)bypass operation performed for the management of moyamoya disease. Previous
      reports have observed that only 1.2-5.7% of the patients who underwent a bypass
      operation for the management of moyamoya disease developed cerebral infarction
      secondary to the WS phenomenon. To date, the WS phenomenon has not been
      objectively proven on imaging studies. We describe a 39-year-old woman who
      presented with right facial palsy and aphasia. Magnetic resonance imaging
      revealed cerebral infarction in the left frontal lobe secondary to moyamoya
      disease. Three days after undergoing the left STA-MCA bypass procedure, she
      showed deterioration in aphasia secondary to the occurrence of cerebral
      hyperperfusion syndrome(CHPS). Diffusion-weighted imaging(DWI)performed on
      postoperative day(POD)1 and 5 showed no area of high signal intensity. DWI
      performed on POD 8 showed an area of high signal intensity in the deep white
      matter of the left parietal lobe outside the range of the craniotomy.
      Postoperative fusion images of computed tomography angiography and DWI performed
      on POD 8 showed that the blood flow through the MCA from the bypass graft and
      that through the posterior cerebral artery crossed each other at the surface of
      the subcortical infarction. In the present case, the WS could be directly
      confirmed on imaging studies, and the cerebral infarction may have occurred
      secondary to WS concomitant with CHPS. Clinicians need to be aware of the WS
      phenomenon even after performing a direct bypass to treat adults with moyamoya
      disease.

PMID- 29449518
TI  - [The Efficacy of Percutaneous Transluminal Angioplasty and Stenting for Traumatic
      Vertebral Artery Dissection due to Cervical Vertebral Fracture].
AB  - A 73-year-old man was admitted at another hospital after a traffic accident. The
      diagnosis was cervical vertebral fracture. Despite conservative treatment, 5 days
      later he manifested dysarthria due to cerebellar infarction and was transferred
      to our hospital. Imaging studies revealed right vertebral arterial dissection at
      the level of the axial fracture. We performed percutaneous transluminal
      angioplasty with stenting to address his subacute vertebral artery dissection
      prior to treating the cervical vertebral fracture using external fixation. His
      clinical course was good;ischemia did not recur after stenting and his dysarthria
      disappeared upon rehabilitation. Cerebral angiograms obtained 6 months later
      revealed no significant in-stent restenosis. While medical management tends to be
      the first-line treatment of traumatic vertebral artery dissection, percutaneous
      transluminal angioplasty with stenting is necessary before treating other
      traumatic lesions to prevent neurologic events.

PMID- 29449519
TI  - [Supratentorial Meningeal Melanoma with Nevus of Ota:A Case Report].
AB  - We present a rare case of supratentorial meningeal melanoma associated with
      ipsilateral nevus of Ota, and a review of the literature. The patient was a 32
      year-old man with a right-sided nevus of Ota, presenting with unconsciousness.
      His CT and MRI scans revealed an extra axial tumor with dural tail signs; no
      lesion was detected on systemic examination. Intraoperatively, the tumor
      demonstrated black hyperpigmentation and was histologically diagnosed as
      malignant melanoma. Following surgery, he received radiotherapy and chemotherapy.
      For over a year and a half, the patient has shown no recurrence of the lesion.

PMID- 29449520
TI  - [A Case of Hypertrophic Pachymeningitis with Symptomatic Venous Congestion due to
      Sinus Stenosis].
AB  - We report a patient with hypertrophic pachymeningitis and symptomatic stenosis of
      the superior sagittal sinus. A 71-year-old man presented with right hemiparesis,
      sensory-dominant aphasia, and right hemispatial neglect that had been worsening
      over 2 weeks. Computed tomography showed isodense crescent-shaped lesions
      deforming the surface of the left cerebral hemisphere, mimicking a subdural
      hematoma with atypical perifocal edema in the left parietal lobe. Magnetic
      resonance imaging showed diffuse thickening of the dura mater with contrast
      enhancement of his left cerebral hemisphere. Histopathological examination of the
      dural specimen obtained by burr-hole surgery revealed mononuclear inflammatory
      cell infiltration, and he was diagnosed with hypertrophic pachymeningitis.
      Dynamic cerebral angiography showed superior sagittal sinus stenosis with reduced
      venous flow through the left parietal lobe. Administration of high-dose steroid
      therapy led to neurological improvement. In the case of a subdural mass with
      atypical parenchymal edema such as a chronic subdural hematoma, other etiology
      should be taken into consideration.

PMID- 29449521
TI  - [Spontaneous Intracranial Hypotension Presenting with De Novo Orthostatic
      Headache and Subdural Hematoma after Meningeal Biopsy].

PMID- 29449522
TI  - [Endoscopic Trans-ventricular Approach for the Treatment of Symptomatic
      Suprasellar Arachnoid Cyst:A Case Report].

PMID- 29449523
TI  - [(2)Usefulness of Cortico-Cortical Evoked Potential in the Diagnosis of
      Epilepsy].

PMID- 29449524
TI  - Transplant Center Variability in Disparities for African-American Kidney
      Transplant Recipients.
AB  - BACKGROUND Disparities research has traditionally focused on patient-level
      variables to ascertain predominant risk factors driving differences in outcomes
      for African-American (AA) kidney transplant recipients. Our objectives were to
      determine the magnitude and impact of transplant center variability for graft
      outcome disparities. MATERIAL AND METHODS This was a retrospective cohort study
      analyzing 25 years of U.S. national transplant registry data at both the patient
      and center levels using univariate descriptive statistics and multivariable
      modeling. RESULTS A total of 257,024 recipients from 191 centers were analyzed;
      AAs represented 31.1% of recipients. After adjusting for baseline
      characteristics, AAs had 42% higher risk of graft loss (aHR 1.42, 95% CI 1.39 to
      1.45; p<0.001). Center variability for graft outcome disparities in AAs was
      significant (race*center interaction term p<0.05), with the aHRs ranging from 0.5
      to 4.9; 46% of centers demonstrated a non-statistically significant disparity
      (aHR p>0.05) and 25% of centers had a large AA disparity (aHR >1.75). In a more
      recent transplant time period (2000-14), overall racial disparities decreased but
      center-level disparities increased in variability. Center-level factors
      significantly associated with increasing disparity included higher acute
      rejection rates, fewer transplants per year, longer length of stay, lower use of
      calcineurin inhibitors (CNI), and lower living donor rates. CONCLUSIONS There is
      evidence of significant center-level variability in graft outcome disparities for
      AA kidney recipients. Further, there appears to be a number of center-level
      factors associated with this variability, including acute rejection rates, CNI
      use, number of transplants per year, and, in recent years, low living donor
      rates.

PMID- 29449525
TI  - Anterior Approach to En Bloc Resection in Left-Sided Retroperitoneal Sarcoma with
      Adjacent Organ Involvement: A Study of 25 Patients in a Single Center.
AB  - BACKGROUND There is no standard surgical approach for the management of
      retroperitoneal sarcoma. The aim of this clinical study was to describe the
      experience of an anterior approach to en bloc resection in left-sided
      retroperitoneal sarcoma with adjacent organ involvement. MATERIAL AND METHODS
      This retrospective clinical study included 25 patients who were diagnosed with
      left-sided retroperitoneal sarcoma and underwent tumor resection at a single
      center between May 2012 and July 2017. All patients had tumors that were adjacent
      to the left colon, pancreas, left kidney, left adrenal gland, and psoas major;
      some of the tumors were adjacent to the diaphragm, stomach, and small intestine.
      An anterior approach was used to remove the left-sided retroperitoneal tumor with
      the adhesive organs en bloc, an approach that is described in detail. The value
      of this surgical approach was evaluated based on the histopathological findings,
      postoperative complications, and patient follow-up. RESULTS The median number of
      resected organs, in addition to the retroperitoneal tumor, was 8 (range, 6-10).
      Complete macroscopic tumor resection was achieved in 23 cases (92%). Twenty-four
      patients (96%) had tumor infiltration of at least one organ or the surrounding
      fat. Three patients (12%) experienced Grade III and IV postoperative morbidities.
      The one-year disease-free survival rate was 91.3% among patients with
      macroscopically complete resections. The one-year overall survival rate was
      83.2%. CONCLUSIONS In selected patients, left-sided retroperitoneal sarcoma
      associated with local organ involvement can be surgically managed using an
      anterior approach with en bloc resection of adjacent organs.

PMID- 29449526
TI  - Raised Serum Levels of Syndecan-1 (CD138), in a Case of Acute Idiopathic Systemic
      Capillary Leak Syndrome (SCLS) (Clarkson's Disease).
AB  - BACKGROUND Systemic capillary leak syndrome (SCLS) (Clarkson's disease) is a rare
      disorder of unknown etiology, characterized by transient episodes of hypotension,
      and the microvascular leak of fluids into the peripheral tissues, resulting in
      edema. Between 80-90% of patients with SCLS have a concomitant monoclonal
      gammopathy. Although translational in vitro studies have implicated vascular
      endothelial barrier dysfunction in the etiology of SCLS, the etiology and disease
      associations in clinical cases remain unknown. CASE REPORT We report a case of
      SCLS in a 49-year-old woman who initially presented with an upper respiratory
      tract infection, which was complicated by edema and compartment syndromes in the
      extremities that required fasciotomies. Serum levels of the cell surface heparan
      sulfate proteoglycan, syndecan-1 (CD138), a measure of endothelial surface
      glycocalyx (ESG) damage, were measured by enzyme-linked immunoassay (ELISA),
      peaked at up to 500 ng/mL (reference range, 50-100 ng/mL) and normalized on
      disease remission. CONCLUSIONS This case report supports the view that damage to
      the microvascular endothelium, has a role in the pathogenesis of acute SCLS. This
      case also indicated that monitoring serum levels of syndecan-1 (CD138) might be
      used to monitor the progression and resolution of episodes of SCLS.

PMID- 29449527
TI  - TR4 nuclear receptor suppresses HCC cell invasion via downregulating the EphA2
      expression.
AB  - Early studies indicated that testicular nuclear receptor 4 (TR4) could function
      as a suppressor in the transcriptional regulation of the HBV core gene
      expression, which might then influence the development of hepatocellular
      carcinoma (HCC). The direct linkage between TR4 and HCC progression, however,
      remained unclear. Here, via a human clinical sample survey, we found that 13 of
      the 18 HCC patients studied had lower TR4 expression in metastatic lesions than
      in matched primary HCC lesions, suggesting that TR4 may play a negative role in
      HCC metastasis. Results from in vitro cell migration/invasion studied confirmed
      that TR4 could suppress HCC cell migration/invasion. Mechanism dissection
      revealed that TR4 might function through downregulating ephrin type-A receptor 2
      (EphA2) expression at the transcriptional level via direct binding to the TR4REs
      located on the 5' promoter of EphA2 to suppress HCC cell migration/invasion.
      Targeting the EphA2 via EphA2-siRNA partially reversed the enhanced HCC cell
      migration/invasion with confirmed TR4 knockdown. Notably, results from
      preclinical studies using in vivo mouse model with orthotopic xenograft of HCC
      LM3 cells also confirmed the in vitro findings. Taking these findings together,
      preclinical studies using multiple in vitro HCC cell lines and an in vivo mouse
      model all led to the conclusion that TR4 may function as a suppressor of HCC
      metastasis and that targeting this newly identified TR4-EphA2 signaling may
      improve our ability to suppress HCC metastasis.

PMID- 29449528
TI  - ALS-related human cortical and motor neurons survival is differentially affected
      by Sema3A.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by cell death of upper and lower motor neurons (MNs). The cause of MN cell loss
      is not completely understood but involves both cell autonomous and non-cell
      autonomous mechanisms. Numerous molecules have been implicated to be involved in
      the death of MNs. One such candidate is semaphorin 3A (Sema3A). In ALS patients,
      Sema3A was shown to be significantly upregulated in the motor cortex and
      downregulated in the spinal cord. In the mouse, Sema3A was shown to be an axon
      repellent molecule for MNs. Sema3A could also induce death of different neuronal
      types that are also repelled by it, including sensory, sympathetic, retinal, and
      cortical neurons. In contrast, astrocyte-specific knockout of Sema3A results in
      motor neuron cell death, consistent with the idea that Sema3A is a survival
      factor for mouse motor neurons. Here, we tested the response of human cortical
      neurons and spinal cord MNs to Sema3A. We found that Sema3A enhances the survival
      of spinal cord MNs. In contrast, Sema3A reduces the survival of cortical neurons.
      Thus, both upregulation of Sema3A in the cortex, or downregulation in the spinal
      cord of ALS patients is likely to directly contribute to MNs cell loss in ALS
      patients.

PMID- 29449529
TI  - Gambogenic acid inhibits fibroblast growth factor receptor signaling pathway in
      erlotinib-resistant non-small-cell lung cancer and suppresses patient-derived
      xenograft growth.
AB  - Erlotinib resistance causes a high degree of lethality in non-small-cell lung
      cancer (NSCLC) patients. The high expression and activation of several receptor
      tyrosine kinases, such as JAK/STAT3, c-Met, and EGFR, play important roles in
      drug resistance. The development of tyrosine kinase inhibitors is urgently
      required in the clinic. Our previous study found that Gambogenic acid (GNA), a
      small molecule derived from the traditional Chinese medicine herb gamboge,
      induced cell death in several NSCLC cell lines through JAK/STAT3 inhibition. In
      this study, we investigated the mechanism of action of GNA in erlotinib-resistant
      NSCLC and patient-derived cells. The inhibition of GNA on FGFR signaling pathway
      was examined using biochemical kinase assays. NSCLC cell lines (HCC827, HCC827
      Erlotinib-resistant, and H1650) and primary cells from patients with NSCLC with
      clinical resistance to erlotinib were treated with GNA, erlotinib, or their
      combination. Both kinase assays and cell- based assays showed that GNA inhibits
      the phosphorylation of multiple kinases in FGFR signaling pathway in NSCLC. The
      combination of GNA and erlotinib significantly attenuates the tumor growth of
      HCC827 and erlotinib-resistant HCC827 xenografts with low toxicity. Importantly,
      GNA significantly suppresses tumor growth in a lung patient-derived xenograft
      (PDX) model with FGFR fusion and low EGFR expression. Our findings provide
      preclinical evidence for using GNA as an FGFR signaling pathway inhibitor to
      overcome erlotinib resistance in NSCLC treatment or to enhance erlotinib efficacy
      when used as a combined administration.

PMID- 29449530
TI  - The type 2 diabetes-associated HMG20A gene is mandatory for islet beta cell
      functional maturity.
AB  - HMG20A (also known as iBRAF) is a chromatin factor involved in neuronal
      differentiation and maturation. Recently small nucleotide polymorphisms (SNPs) in
      the HMG20A gene have been linked to type 2 diabetes mellitus (T2DM) yet neither
      expression nor function of this T2DM candidate gene in islets is known. Herein we
      demonstrate that HMG20A is expressed in both human and mouse islets and that
      levels are decreased in islets of T2DM donors as compared to islets from non
      diabetic donors. In vitro studies in mouse and human islets demonstrated that
      glucose transiently increased HMG20A transcript levels, a result also observed in
      islets of gestating mice. In contrast, HMG20A expression was not altered in
      islets from diet-induced obese and pre-diabetic mice. The T2DM-associated rs7119
      SNP, located in the 3' UTR of the HMG20A transcript reduced the luciferase
      activity of a reporter construct in the human beta 1.1E7 cell line. Depletion of
      Hmg20a in the rat INS-1E cell line resulted in decreased expression levels of its
      neuronal target gene NeuroD whereas Rest and Pax4 were increased. Chromatin
      immunoprecipitation confirmed the interaction of HMG20A with the Pax4 gene
      promoter. Expression levels of Mafa, Glucokinase, and Insulin were also
      inhibited. Furthermore, glucose-induced insulin secretion was blunted in HMG20A
      depleted islets. In summary, our data demonstrate that HMG20A expression in islet
      is essential for metabolism-insulin secretion coupling via the coordinated
      regulation of key islet-enriched genes such as NeuroD and Mafa and that depletion
      induces expression of genes such as Pax4 and Rest implicated in beta cell de
      differentiation. More importantly we assign to the T2DM-linked rs7119 SNP the
      functional consequence of reducing HMG20A expression likely translating to
      impaired beta cell mature function.

PMID- 29449531
TI  - CAR-T cells: the long and winding road to solid tumors.
AB  - Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered
      the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as
      in liquid tumors for the inability to reach and survive in the microenvironment
      surrounding the neoplastic foci. The intricate net of cross-interactions
      occurring between tumor components, stromal and immune cells leads to an
      ineffective anergic status favoring the evasion from the host's defenses. Our
      goal is hereby to trace the road imposed by solid tumors to CAR-T cells,
      highlighting pitfalls and strategies to be developed and refined to possibly
      overcome these hurdles.

PMID- 29449532
TI  - Senescence-associated secretory factors induced by cisplatin in melanoma cells
      promote non-senescent melanoma cell growth through activation of the ERK1/2-RSK1
      pathway.
AB  - Although targeted therapy and immunotherapy greatly improve the outcome of
      melanoma, drug resistance and low response rates still maintain the
      unsubstitutability of traditional chemotherapy. Cisplatin (CDDP) is widely used
      in different types of tumours with high response rates, but it generally has low
      efficiency in melanoma. The mechanisms underpinning the phenomena are not
      sufficiently understood. Here we demonstrated that various melanoma cell lines
      adopted senescence phenotype after CDDP treatment in contrast to the other types
      of tumour cells. CDDP treatment induced melanoma A375 cells into senescence
      through the sequential activation of the DNA damage response and the P53/P21
      pathway. All the senescent melanoma cells induced by CDDP alone or the
      combination of CDDP and dacarbazine developed robust senescence-associated
      secretory phenotype (SASP), that is, the secretion of multiple cytokines. IL
      1alpha was an early component and an upstream regulator of SASP. Similarly, CDDP
      either alone or combined with dacarbazine could induce melanoma cell senescence
      and SASP in either A375 or B16F10 melanoma xenograft mice. The supernatant of
      senescent A375 cells promoted the growth of normal non-senescent A375 cells and
      enhanced their expression and secretion of IL-8 through the activation of the
      ERK1/2-RSK1 pathway. The transplantation of non-senescent and senescent A375
      cells together into nude mice showed accelerated tumour growth compared with
      transplanting non-senescent cells alone; no tumours developed when transplanting
      senescent cells alone. Following CDDP administration in A375-bearing mice, the
      intratumour injection of neutralisation antibodies targeting the SASP factors IL
      1alpha or IL-8 evidently delayed tumour growth. The results suggest that the CDDP
      induced senescent melanoma cells promote non-senescent cells proliferation
      through the activation of ERK1/2-RSK1 pathway by the SASP factors. Cell
      senescence and concomitant SASP may be the particular mechanisms for melanoma to
      resist chemotherapeutics.

PMID- 29449533
TI  - Non-alcoholic fatty liver disease severity is modulated by transglutaminase type
      2.
AB  - Non-alcoholic fatty liver disease (NAFLD) is one of the most important liver
      diseases worldwide. Currently, no effective treatment is available, and NAFLD
      pathogenesis is incompletely understood. Transglutaminase type 2 (TG2) is a
      ubiquitous enzyme whose dysregulation is implicated in the pathogenesis of
      various human diseases. Here we examined the impact of TG2 on NAFLD progression
      using the high-fat-diet-induced model in both wild-type and TG2-deficient mice.
      Animals were fed with a standard chow diet or a high-fat diet (42% of the energy
      from fat) for 16 weeks. Results demonstrated that the absence of a functional
      enzyme, which causes the impairment of autophagy/mitophagy, leads to worsening of
      disease progression. Data were confirmed by pharmacological inhibition of TG2 in
      WT animals. In addition, the analysis of human liver samples from NAFLD patients
      validated the enzyme's involvement in the liver fat disease pathogenesis. Our
      findings strongly suggest that TG2 activation may offer protection in the context
      of NAFLD, thus representing a novel therapeutic target for tackling the NAFLD
      progression.

PMID- 29449534
TI  - TRIM36, a novel androgen-responsive gene, enhances anti-androgen efficacy against
      prostate cancer by inhibiting MAPK/ERK signaling pathways.
AB  - Hormone therapy drugs, such as bicalutamide and enzalutamide, directed against
      prostate cancer focus on androgen receptor (AR) signaling and are initially
      effective, but the disease progresses to lethality as resistance to these drugs
      develops. A method to prolong the drug response time and improve the drug
      efficacy is still unavailable. TRIM36 was reported as a novel androgen signaling
      target gene and is upregulated in prostate cancer. In this study, we found that
      63.4% (64/95) of PCa in TMA expressed the TRIM36 protein. Interestingly, patients
      with negative TRIM36 expression had a shorter biochemical recurrence-free
      survival. TRIM36 expression was significantly associated with the Gleason score
      (P = 0.005), delayed prostate cancer cell cycle progression and inhibited cell
      proliferation in vitro and in vivo, and these effects were mediated via
      inhibition of the MAPK/ERK phosphorylation pathway. Remarkably, we found that
      rescuing the expression of TRIM36 during anti-androgen therapy could improve the
      drug efficacy. Collectively, TRIM36 is a novel androgen-responsive gene, and it
      dramatically enhanced the efficacy of anti-androgen drugs against prostate
      cancer.

PMID- 29449535
TI  - Norisoboldine, a natural AhR agonist, promotes Treg differentiation and
      attenuates colitis via targeting glycolysis and subsequent
      NAD+/SIRT1/SUV39H1/H3K9me3 signaling pathway.
AB  - Norisoboldine (NOR), a natural aryl hydrocarbon receptor (AhR) agonist, has been
      demonstrated to attenuate ulcerative colitis (UC) and induce the generation of
      Treg cells. Under UC condition, hypoxia widely exists in colonic mucosa, and
      secondary changes of microRNAs (miRs) expressions and glycolysis contribute to
      Treg differentiation. At present, we worked for exploring the deep mechanisms for
      NOR-promoted Treg differentiation in hypoxia and its subsequent anti-UC action
      from the angle of AhR/miR or AhR/glycolysis axis. Results showed that NOR
      promoted Treg differentiation in hypoxia and the effect was stronger relative to
      normoxia. It activated AhR in CD4+ T cells under hypoxic microenvironment;
      CH223191 (a specific AhR antagonist) and siAhR-3 abolished NOR-promoted Treg
      differentiation. Furthermore, the progress of glycolysis, levels of Glut1 and
      HK2, and expression of miR-31 rather than miR-219 and miR-490 in CD4+ T cells
      were downregulated by NOR treatment under hypoxic microenvironment. However, HK2
      plasmid but not miR-31 mimic significantly interfered NOR-enhanced Treg
      polarization. In addition, NOR reduced NAD+ and SIRT1 levels, facilitated the
      ubiquitin-proteasomal degradation of SUV39H1 protein, and inhibited the
      enrichment of H3K9me3 at -1, 201 to -1,500 region of Foxp3 promoter in CD4+ T
      cells under hypoxic microenvironment, which was weakened by HK2 plasmid,
      CH223191, and siAhR-3. Finally, the correlation between NOR-mediated activation
      of AhR, repression of glycolysis, regulation of NAD+/SIRT1/SUV39H1/H3K9me3
      signals, induction of Treg cells, and remission of colitis was confirmed in mice
      with DSS-induced colitis by using CH223191 and HK2 plasmid. In conclusion, NOR
      promoted Treg differentiation and then alleviated the development of colitis by
      regulating AhR/glycolysis axis and subsequent NAD+/SIRT1/SUV39H1/H3K9me3
      signaling pathway.

PMID- 29449536
TI  - Impaired autophagic flux is associated with the severity of trauma and the role
      of A2AR in brain cells after traumatic brain injury.
AB  - Recent studies have shown that after traumatic brain injury (TBI), the number of
      autophagosomes is markedly increased in brain cells surrounding the wound;
      however, whether autophagy is enhanced or suppressed by TBI remains
      controversial. In our study, we used a controlled cortical impact system to
      establish models of mild, moderate and severe TBI. In the mild TBI model, the
      levels of autophagy-related protein 6 (Beclin1) and autophagy-related protein 12
      (ATG12)-autophagy-related protein 5 (ATG5) conjugates were increased, indicating
      the enhanced initiation of autophagy. Furthermore, the level of the autophagic
      substrate sequestosome 1 (SQSTM1) was decreased in the ipsilateral cortex. This
      result, together with the results observed in tandem mRFP-GFP-LC3 adeno
      associated virus (AAV)-infected mice, indicates that autophagosome clearance was
      also increased after mild TBI. Conversely, following moderate and severe TBI,
      there was no change in the initiation of autophagy, and autophagosome
      accumulation was observed. Next, we used chloroquine (CQ) to artificially impair
      autophagic flux in the injured cortex of the mild TBI model and found that the
      severity of trauma was obviously exacerbated. In addition, autophagic flux and
      trauma severity were significantly improved in adenosine A2A receptor (A2AR)
      knockout (KO) mice subjected to moderate TBI. Thus, A2AR may be involved in
      regulating the impairment of autophagic flux in response to brain injury. Our
      findings suggest that whether autophagy is increased after TBI is associated with
      whether autophagic flux is impaired, and the impairment of autophagic flux
      exacerbates the severity of trauma. Furthermore, A2AR may be a target for
      alleviating the impairment in autophagic flux after TBI.

PMID- 29449537
TI  - Predictive and preventive significance of AMPK activation on hepatocarcinogenesis
      in patients with liver cirrhosis.
AB  - Metformin has been demonstrated to prevent hepatocellular carcinoma (HCC).
      Metformin acts mainly by phosphorylation of AMPK. However, the phosphorylation
      status of AMPK and its role in the prediction and prevention of HCC in cirrhotic
      patients remains unclear. The phosphorylation status of AMPK (Thr172) was
      determined by immunostaining in tissue microarrays of 426 cirrhotic liver
      tissues. Low expression of p-AMPK was observed in 94 (22.1%) cases. The median
      follow-up time was 87 months. HCC occurrence probability at 1/3/5/10 years after
      Hassab procedure was 3.1/9.6/13.8/30.6% in patients with p-AMPK low expression
      and 0/0.3/0.3/8% in patients with p-AMPK high expression, respectively. HCC
      occurrence risk was significantly higher in patients with p-AMPK low expression
      in univariable analysis (HR, 6.25; 95% CI: 3.36-11.60; P < 0.001) and
      multivariable analysis (HR, 6.0; 95% CI: 3.24-11.10; P < 0.001). An independent
      external cohort validated the significance of p-AMPK low expression. In addition,
      in vivo experiments demonstrated that AMPK activation status was negatively
      related to HCC occurrence and blocking autophagy by chloroquine counteracted the
      protective effect of AMPK phosphorylation. These results present novel insight
      into a critical predictive role of AMPK activation in hepatocarcinogenesis and
      AMPK activation seems to be a potential target for the prevention of
      hepatocellular carcinoma in patients with liver cirrhosis.

PMID- 29449538
TI  - Downregulation of PERK activity and eIF2alpha serine 51 phosphorylation by mTOR
      complex 1 elicits pro-oxidant and pro-death effects in tuberous sclerosis
      deficient cells.
AB  - Oxidative stress determines cell fate through several mechanisms, among which
      regulation of mRNA translation by the phosphorylation of the alpha (alpha)
      subunit of the translation initiation factor eIF2alpha at serine 51 (eIF2alphaP)
      plays a prominent role. Increased eIF2alphaP can contribute to tumor progression
      as well as tumor suppression. While eIF2alphaP is increased in most cells to
      promote survival and adaptation to different forms of stress, we demonstrate that
      eIF2alphaP is reduced in tuberous sclerosis complex 2 (TSC2)-deficient cells
      subjected to oxidative insults. Decreased eIF2alphaP in TSC2-deficient cells
      depends on reactive oxygen species (ROS) production and is associated with a
      reduced activity of the endoplasmic reticulum (ER)-resident kinase PERK owing to
      the hyper-activation of the mammalian target of rapamycin complex 1 (mTORC1).
      Downregulation of PERK activity and eIF2alphaP is accompanied by increased ROS
      production and enhanced susceptibility of TSC2-deficient cells to extrinsic pro
      oxidant stress. The decreased levels of eIF2alphaP delay tumor formation of TSC2
      deficient cells in immune deficient mice, an effect that is significantly
      alleviated in mice subjected to an anti-oxidant diet. Our findings reveal a
      previously unidentified connection between mTORC1 and eIF2alphaP in TSC2
      deficient cells with potential implications in tumor suppression in response to
      oxidative insults.

PMID- 29449539
TI  - G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain
      independent manner.
AB  - Tumor metastasis is the leading cause of death in patients with advanced gastric
      cancer (GC). Limited therapeutic regimens are available for this condition, which
      is associated with a poor prognosis, and the mechanisms underlying tumor
      metastasis remain unclear. In the present study, increased histone
      methyltransferase G9A expression in GC tissues correlated with advanced stage and
      shorter overall survival, and in vitro and in vivo experiments revealed that G9A
      promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced
      G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances
      G9A expression, and upregulated G9A then forms a transcriptional activator
      complex with P300 and GR, thereby promoting ITGB3 expression induced by
      dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated
      increase in ITGB3 expression was not dependent on the SET domain and
      methyltransferase activity of G9A. This study demonstrates that G9A is an
      independent prognostic marker and promotes metastasis in GC, thus suggesting that
      it may be a tumor biomarker and potential therapeutic target in GC.

PMID- 29449540
TI  - S100A4 promotes lung tumor development through beta-catenin pathway-mediated
      autophagy inhibition.
AB  - Autophagy has emerged as a critical pathway in tumor development. S100A4 plays
      important roles in tumor metastasis, but its role in regulating autophagy has not
      been well characterized. In this study, we found that S100A4 was significantly
      upregulated in lung adenocarcinoma tissues. Clinical investigation demonstrated
      that high expression level of S100A4 was associated with tumor size and advanced
      tumor grades of lung adenocarcinoma patients. Moreover, our results revealed that
      extracellular S100A4 or overexpression of S100A4 inhibited starvation-induced
      autophagy and promoted cell proliferation in lung cancer cells in vitro; whereas
      small interfering RNA (siRNA)-mediated suppression of S100A4 increased autophagy
      and reduced cell viability in both A549 and LLC cells. Additionally, S100A4
      inhibited starvation-induced autophagy to promote tumor cell viability via the
      Wnt pathway. Increased expression of beta-catenin consistently led to a decreased
      LC3-II protein abundance. Further, the inhibitory effect of S100A4 on autophagy
      and its promotion role in cell proliferation was abolished in A549 and LLC cells
      using the receptor for advanced glycation end products (RAGE)-specific inhibitor
      (FPS-ZM1). S100A4-deficient mice showed retarded tumor development. This effect
      was well correlated with increased expression of autophagy markers. Our findings
      demonstrate that S100A4 promotes lung tumor development through inhibiting
      autophagy in a beta-catenin signaling and S100A4 receptor RAGE-dependent manner,
      which provides a novel mechanism of S100A4-associated promotion of tumor
      development.

PMID- 29449541
TI  - Long noncoding RNA MEG3 suppresses liver cancer cells growth through inhibiting
      beta-catenin by activating PKM2 and inactivating PTEN.
AB  - Maternally expressed gene 3 (MEG3) encodes an lncRNA which is suggested to
      function as a tumor suppressor and has been showed to involve in a variety of
      cancers. Herein, our findings demonstrate that MEG3 inhibits the malignant
      progression of liver cancer cells in vitro and in vivo. Mechanistically, MEG3
      promotes the expression and maturition of miR122 which targets PKM2. Therefore,
      MEG3 decreases the expression and nuclear location of PKM2 dependent on miR122.
      Furthermore, MEG3 also inhibits CyclinD1 and C-Myc via PKM2 in liver cancer
      cells. On the other hand, MEG3 promotes beta-catenin degradation through
      ubiquitin-proteasome system dependent on PTEN. Strikingly, MEG3 inhibits beta
      catenin activity through PKM2 reduction and PTEN increase. Significantly, we also
      found that excessive beta-catenin abrogated the effect of MEG3 in liver cancer.
      In conclusion, our study for the first time demonstrates that MEG3 acts as a
      tumor suppressor by negatively regulating the activity of the PKM2 and beta
      catenin signaling pathway in hepatocarcinogenesis and could provide potential
      therapeutic targets for the treatment of liver cancer.

PMID- 29449543
TI  - CSF3R-mutated chronic neutrophilic leukemia: long-term outcome in 19 consecutive
      patients and risk model for survival.

PMID- 29449542
TI  - Long non-coding RNAs in ischemic stroke.
AB  - Stroke is one of the leading causes of mortality and disability worldwide.
      Uncovering the cellular and molecular pathophysiological processes in stroke have
      been a top priority. Long non-coding (lnc) RNAs play critical roles in different
      kinds of diseases. In recent years, a bulk of aberrantly expressed lncRNAs have
      been screened out in ischemic stroke patients or ischemia insulted animals using
      new technologies such as RNA-seq, deep sequencing, and microarrays. Nine specific
      lncRNAs, antisense non-coding RNA in the INK4 locus (ANRIL), metastasis-associate
      lung adenocarcinoma transcript 1 (MALAT1), N1LR, maternally expressed gene 3
      (MEG3), H19, CaMK2D-associated transcript 1 (C2dat1), Fos downstream transcript
      (FosDT), small nucleolar RNA host gene 14 (SNHG14), and taurine-upregulated gene
      1 (TUG1), were found increased in cerebral ischemic animals and/or oxygen-glucose
      deprived (OGD) cells. These lncRNAs were suggested to promote cell apoptosis,
      angiogenesis, inflammation, and cell death. Our Gene Ontology (GO) enrichment
      analysis predicted that MEG3, H19, and MALAT1 might also be related to functions
      such as neurogenesis, angiogenesis, and inflammation through mechanisms of gene
      regulation (DNA transcription, RNA folding, methylation, and gene imprinting).
      This knowledge may provide a better understanding of the functions and mechanisms
      of lncRNAs in ischemic stroke. Further elucidating the functions and mechanisms
      of these lncRNAs in biological systems under normal and pathological conditions
      may lead to opportunities for identifying biomarkers and novel therapeutic
      targets of ischemic stroke.

PMID- 29449544
TI  - PEAK1, acting as a tumor promoter in colorectal cancer, is regulated by the
      EGFR/KRas signaling axis and miR-181d.
AB  - PEAK1 is upregulated in multiple human malignancies and has been associated with
      tumor invasion and metastasis, but little is known about the role of PEAK1 in
      colorectal cancer (CRC) progression. We investigated the expression pattern,
      function and regulatory mechanisms of PEAK1 in CRC. Here, we found that PEAK1 is
      overexpressed in CRC tissues and that high PEAK1 expression predicts poor
      survival in colon cancer but not rectal cancer. Functionally, silencing PEAK1
      inhibits cell proliferation, migration, and invasion in vitro and inhibits the
      growth of tumor xenografts in nude mice. Mechanistic studies revealed that PEAK1
      is induced by epidermal growth factor receptor (EGFR) signaling and that PEAK1 is
      required for KRas-induced CRC cell growth and metastasis. Furthermore, we
      demonstrated that miR-181d directly targets PEAK1. Ectopic expression of miR-181d
      reduces the expression of PEAK1 and inhibits the growth and metastasis of CRC
      cells in vitro. Clinically, miR-181d is downregulated in CRC samples, and low miR
      181d is correlated with poor patient survival. Our study demonstrates the
      importance of PEAK1 in CRC progression and suggests a potential mechanism by
      which increasing PEAK1 expression in CRC might be the result of EGFR/KRas signal
      activation and consequent miR-181d repression.

PMID- 29449545
TI  - Transcriptional repression of DNA repair genes is a hallmark and a cause of
      cellular senescence.
AB  - Cellular senescence response is (i) activated by numerous stresses, (ii) is
      characterized by a stable proliferation arrest, and (iii) by a set of specific
      features. Timely regulated senescence is thought to be beneficial, whereas
      chronic senescence such as during normal or premature aging is deleterious as it
      favors most, if not all, age-related diseases. In this study, using in-house or
      publicly available microarray analyses of transcriptomes of senescent cells, as
      well as analyses of the level of expression of several DNA repair genes by RT
      qPCR and immunoblot, we show that repression of DNA repair gene expression is
      associated with cellular senescence. This repression is mediated by the RB/E2F
      pathway and it may play a causal role in senescence induction, as single DNA
      repair gene repression by siRNA induced features of premature senescence.
      Importantly, activating RB independently of direct DNA damage also results in
      repression of DNA repair genes and in the subsequent induction of DNA damage and
      senescence. The dogma is that DNA damage observed during cellular senescence is
      directly provoked by DNA lesions following genotoxic attack (UV, IR, and ROS) or
      by induction of replicative stress upon oncogenic activation. Our in vitro
      results support a largely unsuspected contribution of the loss of DNA repair gene
      expression in the induction and the accumulation of the DNA damage observed in
      most, if not all, kinds of cellular senescence, and thus in the induction of
      cellular senescence. Further demonstration using in vivo models will help to
      generalize our findings.

PMID- 29449546
TI  - A community approach to mortality prediction in sepsis via gene expression
      analysis.
AB  - Improved risk stratification and prognosis prediction in sepsis is a critical
      unmet need. Clinical severity scores and available assays such as blood lactate
      reflect global illness severity with suboptimal performance, and do not
      specifically reveal the underlying dysregulation of sepsis. Here, we present
      prognostic models for 30-day mortality generated independently by three
      scientific groups by using 12 discovery cohorts containing transcriptomic data
      collected from primarily community-onset sepsis patients. Predictive performance
      is validated in five cohorts of community-onset sepsis patients in which the
      models show summary AUROCs ranging from 0.765-0.89. Similar performance is
      observed in four cohorts of hospital-acquired sepsis. Combining the new gene
      expression-based prognostic models with prior clinical severity scores leads to
      significant improvement in prediction of 30-day mortality as measured via AUROC
      and net reclassification improvement index These models provide an opportunity to
      develop molecular bedside tests that may improve risk stratification and
      mortality prediction in patients with sepsis.

PMID- 29449547
TI  - Inference of field reversed configuration topology and dynamics during Alfvenic
      transients.
AB  - Active control of field reversed configuration (FRC) devices requires a method to
      determine the flux surface geometry and dynamic properties of the plasma during
      both transient and steady-state conditions. The current tomography (CT) method
      uses Bayesian inference to determine the plasma current density distribution
      using both the information from magnetic measurements and a physics model in the
      prior. Here we show that, from the inferred current sources, the FRC topology and
      its axial stability properties are readily obtained. When Gaussian process priors
      are used and the forward model is linear, the CT solution involves non-iterative
      matrix operations and is then ideally suited for deterministic real-time
      applications. Because no equilibrium assumptions are used in this case, inference
      of plasma topology and dynamics up to Alfvenic frequencies then becomes possible.
      Inference results for the C-2U device exhibit self-consistency of motions and
      forces during Alfvenic transients, as well as good agreement with plasma imaging
      diagnostics.

PMID- 29449549
TI  - Author Correction: North Atlantic variability and its links to European climate
      over the last 3000 years.
AB  - In the original version of this Article, the third sentence of the first
      paragraph of the "Changes in the input of polar waters into the Labrador Sea"
      section of the Results originally incorrectly read 'During the spring-summer
      months, after the winter convection has ceased in the Labrador Sea, its northwest
      boundary currents (the EGC and IC) support restratification of the surface ocean
      through lateral transport.' The correct version states 'northeast' instead of
      'northwest'. The fifth sentence of the second paragraph of the same section
      originally incorrectly read "In contrast, in the western section of the Nordic
      Seas, under the presence of warm Atlantic waters of the Norwegian Current, Nps
      was found to calcify deeper in the water column (100-200 m), whereas in the east
      under the influence of the EGC polar waters it calcified closer to the surface at
      a similar depth as Tq23." The correct version states 'eastern' instead of
      'western' and 'west' instead of 'east'.The seventh sentence of the same paragraph
      originally incorrectly read "Small/large differences in Deltadelta18ONps-Tq
      indicating increased/decreased presence of warm and salty Atlantic IC waters vs.
      polar EGC waters in the upper water column, respectively." The correct version
      starts 'Large/small' rather than 'Small/large'.These errors have been corrected
      in both the PDF and HTML versions of the Article.

PMID- 29449550
TI  - Meeting Report: The 8th Barossa Meeting-Cell Signaling in Cancer Medicine in the
      Barossa Valley, Australia.

PMID- 29449552
TI  - Author Correction: How to probe the spin contribution to momentum relaxation in
      topological insulators.
AB  - The original version of this Article contained an error in the spelling of the
      author Benjamin H. Williams, which was incorrectly given as Benjamin H. Willams.
      This has now been corrected in both the PDF and HTML versions of the Article.

PMID- 29449553
TI  - Nuclear factor 90 promotes angiogenesis by regulating HIF-1alpha/VEGF-A
      expression through the PI3K/Akt signaling pathway in human cervical cancer.
AB  - Vascular endothelial growth factor A (VEGF-A), a fundamental component of
      angiogenesis, provides nutrients and oxygen to solid tumors, and enhances tumor
      cell survival, invasion, and migration. Nuclear factor 90 (NF90), a double
      stranded RNA-binding protein, is strongly expressed in several human cancers,
      promotes tumor growth by reducing apoptosis, and increasing cell cycle process.
      The mechanisms by which cervical cancer cells inducing VEGF-A expression and
      angiogenesis upon NF90 upregulation remain to be fully established. We
      demonstrated that NF90 is upregulated in human cervical cancer specimens and the
      expression of NF90 is paralleled with that of VEGF-A under hypoxia. The
      expressions of hypoxia inducible factor-1alpha (HIF-1alpha) and VEGF-A are
      downregulated upon NF90 knockdown, which can be rescued by ectopic expression of
      NF90. Suppression of NF90 decreases the tube formation and cell migration of
      HUVECs. Moreover, the PI3K/Akt signaling pathway participates in the regulation.
      Knockdown of NF90 also reduces the tumor growth and angiogenesis of cervical
      cancer cell line in the mouse xenograft model. Taken together, suppression of
      NF90 in cervical cancer cell lines can decrease VEGF-A expression, inhibit
      angiogenesis, and reduce tumorigenic capacity in vivo.

PMID- 29449551
TI  - Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in
      Trypanosoma and human.
AB  - Spermatogenesis defects concern millions of men worldwide, yet the vast majority
      remains undiagnosed. Here we report men with primary infertility due to multiple
      morphological abnormalities of the sperm flagella with severe disorganization of
      the sperm axoneme, a microtubule-based structure highly conserved throughout
      evolution. Whole-exome sequencing was performed on 78 patients allowing the
      identification of 22 men with bi-allelic mutations in DNAH1 (n = 6), CFAP43 (n =
      10), and CFAP44 (n = 6). CRISPR/Cas9 created homozygous CFAP43/44 male mice that
      were infertile and presented severe flagellar defects confirming the human
      genetic results. Immunoelectron and stimulated-emission-depletion microscopy
      performed on CFAP43 and CFAP44 orthologs in Trypanosoma brucei evidenced that
      both proteins are located between the doublet microtubules 5 and 6 and the
      paraflagellar rod. Overall, we demonstrate that CFAP43 and CFAP44 have a similar
      structure with a unique axonemal localization and are necessary to produce
      functional flagella in species ranging from Trypanosoma to human.

PMID- 29449555
TI  - Intravenous injections of the oncolytic virus M1 as a novel therapy for muscle
      invasive bladder cancer.
AB  - Muscle-invasive bladder cancer (MIBC) is associated with low survival and high
      recurrence rates even in cases in which patients receive systemic treatments,
      such as surgery and chemotherapy. Here, we found that a naturally existing
      alphavirus, namely, M1, selectively kills bladder cancer cells but not normal
      cells, findings supported by our observations of changes in viral replication and
      MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed
      that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive
      bladder cancer cells and high levels in resistant cells. Knocking down ZC3HAV1
      (ZAP), an antiviral factor in ISGs, restores M1 virus reactivity in resistant
      cells, and overexpressing ZAP partially reverses M1 virus-induced decreases in
      cell viability in sensitive cells. In orthotopic MIBC mice, tail vein injections
      of M1 significant inhibit tumor growth and prolong survival period, antitumor
      effects of M1 are stronger than those of the first-line chemotherapy agent
      cisplatin (CDDP). Treated tumors display enhanced cleaved-caspase-3 signals,
      which are representative of cell apoptosis, and decreased Ki-67 signals, which
      are representative of cell proliferation. Moreover, tissue microarray (TMA)
      analyses of clinical tumor specimens revealed that up to 45.6% of cases of MIBC
      presented with low ZAP expression, a finding that is prevalent in advanced MIBC.
      Our results indicate that the oncolytic virus M1 is a novel agent capable of
      functioning as a precise and effective therapy for MIBC.

PMID- 29449554
TI  - Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed
      genes.
AB  - Introduction of synthetic circuits into microbes creates competition between
      circuit and host genes for shared cellular resources, such as ribosomes. This can
      lead to the emergence of unwanted coupling between the expression of different
      circuit genes, complicating the design process and potentially leading to circuit
      failure. By expressing a synthetic 16S rRNA with altered specificity, we can
      partition the ribosome pool into host-specific and circuit-specific activities.
      We show mathematically and experimentally that the effects of resource
      competition can be alleviated by targeting genes to different ribosomal pools.
      This division of labour can be used to increase flux through a metabolic pathway.
      We develop a model of cell physiology which is able to capture these observations
      and use it to design a dynamic resource allocation controller. When implemented,
      this controller acts to decouple genes by increasing orthogonal ribosome
      production as the demand for translational resources by a synthetic circuit
      increases.

PMID- 29449556
TI  - CD1d-dependent immune suppression mediated by regulatory B cells through
      modulations of iNKT cells.
AB  - Regulatory B cells (Breg) express high levels of CD1d that presents lipid
      antigens to invariant natural killer T (iNKT) cells. The function of CD1d in Breg
      biology and iNKT cell activity during inflammation remains unclear. Here we show,
      using chimeric mice, cell depletion and adoptive cell transfer, that CD1d-lipid
      presentation by Bregs induces iNKT cells to secrete interferon (IFN)-gamma to
      contribute, partially, to the downregulation of T helper (Th)1 and Th17-adaptive
      immune responses and ameliorate experimental arthritis. Mice lacking CD1d
      expressing B cells develop exacerbated disease compared to wild-type mice, and
      fail to respond to treatment with the prototypical iNKT cell agonist alpha
      galactosylceramide. The absence of lipid presentation by B cells alters iNKT cell
      activation with disruption of metabolism regulation and cytokine responses. Thus,
      we identify a mechanism by which Bregs restrain excessive inflammation via lipid
      presentation.

PMID- 29449558
TI  - Interventions to enhance the adoption of asthma self-management behaviour in the
      South Asian and African American population: a systematic review.
AB  - South Asian and other minority communities suffer poorer asthma outcomes, have a
      higher rate of unscheduled care and benefit less from most existing self
      management interventions when compared to the majority population. Possible
      reasons for these differences include failure to implement asthma self-management
      strategies, or that strategies implemented were inappropriate for their needs;
      alternatively, they may relate to the minority and/or lower socioeconomic status
      of these populations. We aimed to synthesise evidence from randomised controlled
      trials for asthma self-management in South Asian and Black populations from
      different sociocultural contexts, and identify barriers and facilitators to
      implementing self-management. We systematically searched eight electronic
      databases, and research registers, and manually searched relevant journals and
      reference lists of reviews. Seventeen trials met the inclusion criteria and were
      analysed narratively. We found two culturally targeted interventions compared to
      fifteen culturally modified interventions. Interventions used diverse self
      management strategies; education formed a central component. Interventions in
      South Asian and African-American minority communities were less effective than
      interventions delivered in indigenous populations in South Asia, though the
      latter trials were at higher risk of bias. Education, with continuous
      professional support, was common to most interventions. Facilitators to asthma
      self-management included: ensuring culturally/linguistically appropriate
      education, adapting to learning styles, addressing daily stressors/social support
      and generic self-management strategies. In conclusion, when developing and
      evaluating self-management interventions aimed at different cultures, the
      influence of sociocultural contexts (including whether patients are from a
      minority or indigenous population) can be important for the conceptualisation of
      culture and customisation of self-management strategies.

PMID- 29449557
TI  - Differential patterns of contextual organization of memory in first-episode
      psychosis.
AB  - Contextual information is used to support and organize episodic memory. Prior
      research has reliably shown memory deficits in psychosis; however, little
      research has characterized how this population uses contextual information during
      memory recall. We employed an approach founded in a computational framework of
      free recall to quantify how individuals with first episode of psychosis (FEP, N =
      97) and controls (CON, N = 55) use temporal and semantic context to organize
      memory recall. Free recall was characterized using the Hopkins Verbal Learning
      Test-Revised (HVLT-R). We compared FEP and CON on three measures of free recall:
      proportion recalled, temporal clustering, and semantic clustering. Measures of
      temporal/semantic clustering quantified how individuals use contextual
      information to organize memory recall. We also assessed to what extent these
      measures relate to antipsychotic use and differentiated between different types
      of psychosis. We also explored the relationship between these measures and
      intelligence. In comparison to CON, FEP had reduced recall and less temporal
      clustering during free recall (p < 0.05, Bonferroni-corrected), and showed a
      trend towards greater semantic clustering (p = 0.10, Bonferroni-corrected).
      Within FEP, antipsychotic use and diagnoses did not differentiate between free
      recall accuracy or contextual organization of memory. IQ was related to free
      recall accuracy, but not the use of contextual information during recall in
      either group (p < 0.05, Bonferroni-corrected). These results show that in
      addition to deficits in memory recall, FEP differed in how they organize memories
      compared to CON.

PMID- 29449559
TI  - Downregulation of SREBP inhibits tumor growth and initiation by altering cellular
      metabolism in colon cancer.
AB  - Sterol regulatory element-binding proteins (SREBPs) belong to a family of
      transcription factors that regulate the expression of genes required for the
      synthesis of fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c,
      and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are
      derived from a single gene through the use of alternative transcription start
      sites. Here we investigated the role of SREBP-mediated lipogenesis in regulating
      tumor growth and initiation in colon cancer. Knockdown of either SREBP1 or SREBP2
      decreased levels of fatty acids as a result of decreased expression of SREBP
      target genes required for lipid biosynthesis in colon cancer cells. Bioenergetic
      analysis revealed that silencing SREBP1 or SREBP2 expression reduced the
      mitochondrial respiration, glycolysis, as well as fatty acid oxidation indicating
      an alteration in cellular metabolism. Consequently, the rate of cell
      proliferation and the ability of cancer cells to form tumor spheroids in
      suspension culture were significantly decreased. Similar results were obtained in
      colon cancer cells in which the proteolytic activation of SREBP was blocked.
      Importantly, knockdown of either SREBP1 or SREBP2 inhibited xenograft tumor
      growth in vivo and decreased the expression of genes associated with cancer stem
      cells. Taken together, our findings establish the molecular basis of SREBP
      dependent metabolic regulation and provide a rationale for targeting lipid
      biosynthesis as a promising approach in colon cancer treatment.

PMID- 29449560
TI  - Knockout of zebrafish interleukin 7 receptor (IL7R) by the CRISPR/Cas9 system
      delays retinal neurodevelopment.
AB  - Interleukin 7 receptor (il7r), a transmembrane receptor, belongs to the type I
      cytokine receptor family. Il7r is involved in the pathogenesis of
      neurodegenerative disorders, such as multiple sclerosis. Targeted knockdown of
      il7r leads to delayed myelination, highlighting the potential role of il7r in the
      development of the nervous system. Zebrafish is an ideal model for the study of
      neurogenesis; moreover, the il7r gene is highly conserved between zebrafish and
      human. The aim of the present study was to investigate the novel function of il7r
      in neurogenesis. First, an il7r -/- homozygous mutant line was generated by
      clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9
      (CRISPR/Cas9) technology. Second, the gross development of il7r-/- mutants
      revealed remarkably smaller eyes and delayed retinal neurodifferentiation. Third,
      microarray analysis revealed that genes associated with the phototransduction
      signalling pathway were strongly down-regulated in il7r -/- mutants. Finally, the
      results from behavioural tests indicated that visual function was impaired in
      il7r -/- mutant larvae. Overall, our data demonstrate that a lack of il7r retards
      the development of the retina. Thus, il7r is an essential molecule for
      maintaining normal retinal development in zebrafish.

PMID- 29449548
TI  - Common surgical procedures in pilonidal sinus disease: A meta-analysis, merged
      data analysis, and comprehensive study on recurrence.
AB  - We systematically searched available databases. We reviewed 6,143 studies
      published from 1833 to 2017. Reports in English, French, German, Italian, and
      Spanish were considered, as were publications in other languages if definitive
      treatment and recurrence at specific follow-up times were described in an English
      abstract. We assessed data in the manner of a meta-analysis of RCTs; further we
      assessed non-RCTs in the manner of a merged data analysis. In the RCT analysis
      including 11,730 patients, Limberg & Dufourmentel operations were associated with
      low recurrence of 0.6% (95%CI 0.3-0.9%) 12 months and 1.8% (95%CI 1.1-2.4%)
      respectively 24 months postoperatively. Analysing 89,583 patients from RCTs and
      non-RCTs, the Karydakis & Bascom approaches were associated with recurrence of
      only 0.2% (95%CI 0.1-0.3%) 12 months and 0.6% (95%CI 0.5-0.8%) 24 months
      postoperatively. Primary midline closure exhibited long-term recurrence up to
      67.9% (95%CI 53.3-82.4%) 240 months post-surgery. For most procedures, only a few
      RCTs without long term follow up data exist, but substitute data from numerous
      non-RCTs are available. Recurrence in PSD is highly dependent on surgical
      procedure and by follow-up time; both must be considered when drawing conclusions
      regarding the efficacy of a procedure.

PMID- 29449561
TI  - Discovery of a magnetic conductive interface in PbZr0.2Ti0.8O3 /SrTiO3
      heterostructures.
AB  - Emergent physical properties often arise at interfaces of complex oxide
      heterostructures due to the interplay between various degrees of freedom,
      especially those with polar discontinuities. It is desirable to explore if these
      structures may generate pure and controllable spin currents, which are needed to
      attain unmatched performance and energy efficiency in the next-generation
      spintronic devices. Here we report the emergence of a spin-polarized two
      dimensional electron gas (SP-2DEG) at the interface of two insulators, SrTiO3 and
      PbZr0.2Ti0.8O3. This SP-2DEG is strongly localized at the interfacial Ti atoms,
      due to the interplay between Coulomb interaction and band bending, and can be
      tuned by the ferroelectric polarization. Our findings open a door for engineering
      ferroelectric/insulator interfaces to create tunable ferroic orders for
      magnetoelectric device applications and provide opportunities for designing
      multiferroic materials in heterostructures.

PMID- 29449562
TI  - Chir99021 and Valproic acid reduce the proliferative advantage of Apc mutant
      cells.
AB  - More than 90% of colorectal cancers carry mutations in Apc that drive
      tumourigenesis. A 'just-right' signalling model proposes that Apc mutations
      stimulate optimal, but not excessive Wnt signalling, resulting in a growth
      advantage of Apc mutant over wild-type cells. Reversal of this growth advantage
      constitutes a potential therapeutic approach. We utilised intestinal organoids to
      compare the growth of Apc mutant and wild-type cells. Organoids derived from Apc
      Min/+ mice recapitulate stages of intestinal polyposis in culture. They
      eventually form spherical cysts that reflect the competitive growth advantage of
      cells that have undergone loss of heterozygosity (LOH). We discovered that this
      emergence of cysts was inhibited by Chiron99021 and Valproic acid, which
      potentiates Wnt signalling. Chiron99021 and Valproic acid restrict the growth
      advantage of Apc mutant cells while stimulating that of wild-type cells,
      suggesting that excessive Wnt signalling reduces the relative fitness of Apc
      mutant cells. As a proof of concept, we demonstrated that Chiron99021-treated Apc
      mutant organoids were rendered susceptible to TSA-induced apoptosis, while wild
      type cells were protected.

PMID- 29449564
TI  - Aggregation-fragmentation and individual dynamics of active clusters.
AB  - A remarkable feature of active matter is the propensity to self-organize. One
      striking instance of this ability to generate spatial structures is the cluster
      phase, where clusters broadly distributed in size constantly move and evolve
      through particle exchange, breaking or merging. Here we propose an exhaustive
      description of the cluster dynamics in apolar active matter. Exploiting large
      statistics gathered on thousands of Janus colloids, we measure the aggregation
      and fragmentation rates and rationalize the resulting cluster size distribution
      and fluctuations. We also show that the motion of individual clusters is entirely
      consistent with a model positing random orientation of colloids. Our findings
      establish a simple, generic model of cluster phase, and pave the way for a
      thorough understanding of clustering in active matter.

PMID- 29449563
TI  - Cinacalcet-mediated activation of the CaMKKbeta-LKB1-AMPK pathway attenuates
      diabetic nephropathy in db/db mice by modulation of apoptosis and autophagy.
AB  - Apoptosis and autophagy are harmoniously regulated biological processes for
      maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as
      a metabolic sensor to coordinate cellular survival and function in various
      organs, including the kidney. We investigated the renoprotective effects of
      cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs),
      murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes,
      cinacalcet decreased oxidative stress and apoptosis and increased autophagy that
      were attributed to the increment of intracellular Ca2+ concentration and the
      phosphorylation of Ca2+/calmodulin-dependent protein kinase kinasebeta
      (CaMKKbeta)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including
      the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in
      superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein
      expression. Interestingly, intracellular chelator BAPTA-AM reversed cinacalcet
      induced CaMKKbeta elevation and LKB1 phosphorylation. Cinacalcet reduced
      albuminuria without influencing either blood glucose or Ca2+ concentration and
      ameliorated diabetes-induced renal damage, which were related to the increased
      expression of calcium-sensing receptor and the phosphorylation of CaMKKbeta-LKB1.
      Subsequent activation of AMPK was followed by the activation of peroxisome
      proliferator-activated receptor gamma coactivator-1alpha and phospho-Ser1177eNOS
      nitric oxide, resulting in a decrease in apoptosis and oxidative stress as well
      as an increase in autophagy.Our results suggest that cinacalcet increases
      intracellular Ca2+ followed by an activation of CaMKKbeta-LKB1-AMPK signaling in
      GECs and podocytes in the kidney, which provides a novel therapeutic means for
      type 2 diabetic nephropathy by modulation of apoptosis and autophagy.

PMID- 29449566
TI  - First evidence of an extensive Acheulean large cutting tool accumulation in
      Europe from Porto Maior (Galicia, Spain).
AB  - We describe a European Acheulean site characterised by an extensive accumulation
      of large cutting tools (LCT). This type of Lower Paleolithic assemblage, with
      dense LCT accumulations, has only been found on the African continent and in the
      Near East until now. The identification of a site with large accumulations of
      LCTs favours the hypothesis of an African origin for the Acheulean of Southwest
      Europe. The lithic tool-bearing deposits date back to 293-205 thousand years ago.
      Our chronological findings confirm temporal overlap between sites with clear
      "African" Acheulean affinities and Early Middle Paleolithic sites found elsewhere
      in the region. These complex technological patterns could be consistent with the
      potential coexistence of different human species in south-western Europe during
      the Middle Pleistocene.

PMID- 29449565
TI  - Amphibian chytridiomycosis outbreak dynamics are linked with host skin bacterial
      community structure.
AB  - Host-associated microbes are vital for combatting infections and maintaining
      health. In amphibians, certain skin-associated bacteria inhibit the fungal
      pathogen Batrachochytrium dendrobatidis (Bd), yet our understanding of host
      microbial ecology and its role in disease outbreaks is limited. We sampled skin
      associated bacteria and Bd from Pyrenean midwife toad populations exhibiting
      enzootic or epizootic disease dynamics. We demonstrate that bacterial communities
      differ between life stages with few shared taxa, indicative of restructuring at
      metamorphosis. We detected a significant effect of infection history on metamorph
      skin microbiota, with reduced bacterial diversity in epizootic populations and
      differences in community structure and predicted function. Genome sequencing of
      Bd isolates supports a single introduction to the Pyrenees and reveals no
      association between pathogen genetics and epidemiological trends. Our findings
      provide an ecologically relevant insight into the microbial ecology of amphibian
      skin and highlight the relative importance of host microbiota and pathogen
      genetics in predicting disease outcome.

PMID- 29449567
TI  - Systematic analysis of protein turnover in primary cells.
AB  - A better understanding of proteostasis in health and disease requires robust
      methods to determine protein half-lives. Here we improve the precision and
      accuracy of peptide ion intensity-based quantification, enabling more accurate
      protein turnover determination in non-dividing cells by dynamic SILAC-based
      proteomics. This approach allows exact determination of protein half-lives
      ranging from 10 to >1000 h. We identified 4000-6000 proteins in several non
      dividing cell types, corresponding to 9699 unique protein identifications over
      the entire data set. We observed similar protein half-lives in B-cells, natural
      killer cells and monocytes, whereas hepatocytes and mouse embryonic neurons show
      substantial differences. Our data set extends and statistically validates the
      previous observation that subunits of protein complexes tend to have coherent
      turnover. Moreover, analysis of different proteasome and nuclear pore complex
      assemblies suggests that their turnover rate is architecture dependent. These
      results illustrate that our approach allows investigating protein turnover and
      its implications in various cell types.

PMID- 29449568
TI  - Binge Alcohol Exposure Causes Neurobehavioral Deficits and GSK3beta Activation in
      the Hippocampus of Adolescent Rats.
AB  - Heavy alcohol exposure causes profound damage to the adolescent brain,
      particularly the hippocampus, which underlie some behavioral deficits. However,
      the underlying molecular mechanisms remain inconclusive. The current study sought
      to determine whether binge alcohol exposure affects the hippocampus-related
      behaviors and key signaling proteins that may mediate alcohol neurotoxicity in
      adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and
      doublecortin-positive cells in the hippocampus. Alcohol also induced
      neurodegeneration which was confirmed by ultrastructural analysis by electronic
      microscopy and was accompanied with the activation of microglia. Binge alcohol
      exposure impaired spatial learning and memory which was evaluated by the Morris
      water maze. However, alcohol did not alter the spontaneous locomotor activity
      which was determined by the open field test. GSK3beta is a multi-function
      serine/threonine protein kinase regulating both neuronal survival and
      neurogenesis and plays an important role in various neurodegenerative disorders.
      We have previously shown that GSK3beta is a key mediator of alcohol-induced
      neuron apoptosis in the developing brain. We showed here binge alcohol exposure
      caused GSK3beta activation by inducing dephosphorylation at Ser9 without
      affecting the phosphorylation of Tyr216 in the hippocampus. Thus, GSK3beta may be
      involved in binge alcohol exposure-induced neuronal damage to the adolescent
      hippocampus.

PMID- 29449569
TI  - Threshold driven contagion on weighted networks.
AB  - Weighted networks capture the structure of complex systems where interaction
      strength is meaningful. This information is essential to a large number of
      processes, such as threshold dynamics, where link weights reflect the amount of
      influence that neighbours have in determining a node's behaviour. Despite
      describing numerous cascading phenomena, such as neural firing or social
      contagion, the modelling of threshold dynamics on weighted networks has been
      largely overlooked. We fill this gap by studying a dynamical threshold model over
      synthetic and real weighted networks with numerical and analytical tools. We show
      that the time of cascade emergence depends non-monotonously on weight
      heterogeneities, which accelerate or decelerate the dynamics, and lead to non
      trivial parameter spaces for various networks and weight distributions. Our
      methodology applies to arbitrary binary state processes and link properties, and
      may prove instrumental in understanding the role of edge heterogeneities in
      various natural and social phenomena.

PMID- 29449570
TI  - In-situ visualization of sound-induced otolith motion using hard X-ray phase
      contrast imaging.
AB  - Regarding the basics of ear structure-function relationships in fish, the actual
      motion of the solid otolith relative to the underlying sensory epithelium has
      rarely been investigated. Otolith motion has been characterized based on a few
      experimental studies and on approaches using mathematical modeling, which have
      yielded partially conflicting results. Those studies either predicted a simple
      back-and-forth motion of the otolith or a shape-dependent, more complex motion.
      Our study was designed to develop and test a new set-up to generate experimental
      data on fish otolith motion in-situ. Investigating the basic parameters of
      otolith motion requires an approach with high spatial and temporal resolution. We
      therefore used hard X-ray phase contrast imaging (XPCI). We compared two
      anatomically well-studied cichlid species, Steatocranus tinanti and Etroplus
      maculatus, which, among other features, differ in the 3D shape of their otoliths.
      In a water-filled tank, we presented a pure tone of 200 Hz to 1) isolated
      otoliths embedded in agarose serving as a simple model or 2) to a fish (otoliths
      in-situ). Our new set-up successfully visualized the motion of otoliths in-situ
      and therefore paves the way for future studies evaluating the principles of
      otolith motion.

PMID- 29449571
TI  - An in silico argument for mitochondrial microRNA as a determinant of primary non
      function in liver transplantation.
AB  - Mitochondria have their own genomic, transcriptomic and proteomic machinery but
      are unable to be autonomous, needing both nuclear and mitochondrial genomes. The
      aim of this work was to use computational biology to explore the involvement of
      Mitochondrial microRNAs (MitomiRs) and their interactions with the mitochondrial
      proteome in a clinical model of primary non function (PNF) of the donor after
      cardiac death (DCD) liver. Archival array data on the differential expression of
      miRNA in DCD PNF was re-analyzed using a number of publically available
      computational algorithms. 10 MitomiRs were identified of importance in DCD PNF, 7
      with predicted interaction of their seed sequence with the mitochondrial
      transcriptome that included both coding, and non coding areas of the
      hypervariability region 1 (HVR1) and control region. Considering miRNA regulation
      of the nuclear encoded mitochondrial proteome, 7 hypothetical small proteins were
      identified with homolog function that ranged from co-factor for formation of ATP
      Synthase, REDOX balance and an importin/exportin protein. In silico,
      unconventional seed interactions, both non canonical and alternative seed sites,
      appear to be of greater importance in MitomiR regulation of the mitochondrial
      genome. Additionally, a number of novel small proteins of relevance in
      transplantation have been identified which need further characterization.

PMID- 29449572
TI  - Optimising the decellularization of human elastic cartilage with trypsin for
      future use in ear reconstruction.
AB  - Decellularized scaffolds can induce chondrogenic differentiation of stem cells.
      This study compares different methods to optimise the decellularization of
      auricular cartilage. The process consisted of an initial 12 hour dry freeze thaw
      which froze the cartilage specimens in an empty tube at -20  degrees C. Samples
      were allowed to thaw at room temperature followed by submersion in phosphate
      buffer solution in which they were frozen at -20  degrees C for a 12 hour period.
      They were then allowed to thaw at room temperature as before. Protocol A
      subsequently involved subjecting specimens to both deoxyribonuclease and sodium
      deoxycholate. Protocol B and C were adaptations of this using 0.25% trypsin (7
      cycles) and a 0.5 molar solution of ethylenediaminetetraacetic acid (3 hours for
      each cycle) respectively as additional steps. Trypsin accelerated the
      decellularization process with a reduction in DNA content from 55.4 ng/MUL
      (native) to 17.3 ng/MUL (P-value < 0.05) after 14 days. Protocol B showed a
      faster reduction in DNA content when compared with protocol A. In comparison to
      protocol C after 14 days, trypsin also showed greater decellularization with a
      mean difference of 11.7 ng/MUL (P-value < 0.05). Histological analysis with H&E
      and DAPI confirmed depletion of cells at 14 days with trypsin.

PMID- 29449573
TI  - Nuclear targeting of the betanodavirus B1 protein via two arginine-rich domains
      induces G1/S cell cycle arrest mediated by upregulation of p53/p21.
AB  - The molecular functions of betanodavirus non-structural protein B and its role in
      host cell survival remain unclear. In the present study, we examined the roles of
      specific nuclear targeting domains in B1 localization as well as the effect of B1
      nuclear localization on the cell cycle and host cell survival. The B1 protein of
      the Red spotted grouper nervous necrosis virus (RGNNV) was detected in GF-1
      grouper cells as early as 24 hours post-infection (hpi). Using an EYFP-B1 fusion
      construct, we observed nuclear localization of the B1 protein (up to 99%) in GF-1
      cells at 48 hpi. The nuclear localization of B1 was mediated by two arginine-rich
      nuclear targeting domains (B domain: 46RRSRR51; C domain: 63RDKRPRR70) and domain
      C was more important than domain B in this process. B1 nuclear localization
      correlated with upregulation of p53 and p21(wef1/cip1); downregulation of Cyclin
      D1, CDK4 and Mdm2; and G1/S cell cycle arrest in GF-1 cells. In conclusion,
      nuclear targeting of the RGNNV B1 protein via two targeting domains causes cell
      cycle arrest by up-regulating p53/p21 and down-regulating Mdm2, thereby
      regulating host cell survival.

PMID- 29449574
TI  - Upregulation of FOXM1 in a subset of relapsed myeloma results in poor outcome.

PMID- 29449576
TI  - Lizards ran bipedally 110 million years ago.
AB  - Four heteropod lizard trackways discovered in the Hasandong Formation (Aptian
      early Albian), South Korea assigned to Sauripes hadongensis, n. ichnogen., n.
      ichnosp., which represents the oldest lizard tracks in the world. Most tracks are
      pes tracks (N = 25) that are very small, average 22.29 mm long and 12.46 mm wide.
      The pes tracks show "typical" lizard morphology as having curved digit imprints
      that progressively increase in length from digits I to IV, a smaller digit V that
      is separated from the other digits by a large interdigital angle. The manus track
      is 19.18 mm long and 19.23 mm wide, and shows a different morphology from the
      pes. The predominant pes tracks, the long stride length of pes, narrow trackway
      width, digitigrade manus and pes prints, and anteriorly oriented long axis of the
      fourth pedal digit indicate that these trackways were made by lizards running
      bipedally, suggesting that bipedality was possible early in lizard evolution.

PMID- 29449578
TI  - Probing Conformal Invariant of Non-unitary Two-Dimensional Systems by Central
      Spin Decoherence.
AB  - Universality classes of non-unitary critical theories in two-dimensions are
      characterized by the central charge. However, experimental determination of the
      central charge of a non-unitary critical theory has not been done before because
      of the intrinsic difficulty that complex parameters usually occur in non-unitary
      theory, which is not physical. Here we propose to extract the effective central
      charge of the non-unitary critical point of a two-dimensional lattice model from
      the quantum coherence measurement of a probe spin which is coupled to the lattice
      model. A recent discovery shows that quantum coherence of a probe spin which is
      coupled to a bath is proportional to the partition function of the bath with a
      complex parameter. Thus the effective central charge of a non-unitary conformal
      field theory may be extracted from quantum coherence measurement of a probe spin
      which is coupled to a bath. We have applied the method to the Yang-Lee edge
      singularity of the two-dimensional Ising model and extracted the effective
      central charge of the Yang-Lee edge singularity with good precision and tested
      other predictions of non-unitary conformal field theory. This work paves the way
      for the first experimental observation of the effective central charge of non
      unitary conformal field theory.

PMID- 29449577
TI  - Neutralization of IL-15 abrogates experimental immune-mediated cholangitis in
      diet-induced obese mice.
AB  - Obesity is a global epidemic affecting chronic inflammatory diseases. Primary
      sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that can
      occur as an extraintestinal manifestation of inflammatory bowel disease (IBD).
      Previously we reported that patients with PSC who are obese have a higher risk of
      advanced liver disease. Currently it is unknown how obesity accelerates or
      worsens PSC. We evaluated the progression of PSC in an antigen-driven cholangitis
      mouse model of diet-induced obesity. Obesity was induced in our murine model of
      immune-mediated cholangitis (OVAbil). OVAbil mice were fed standard chow or high
      fat/sucrose diet for twelve weeks followed by induction of biliary inflammation
      by OVA-specific T cell transfer. Histopathological damage in portal tracts was
      scored and serum collected. Neutralizing antibodies against IL-15 were
      administered daily until study termination. Obese mice developed exacerbated
      liver inflammation and damage. Immune cell phenotyping in liver revealed greater
      numbers of neutrophils and CD8+ T cells in obese mice. Higher levels of cytokines
      and chemokines were found in obese mice with cholangitis. Immuno-neutralizing
      antibodies against IL-15 greatly attenuated cholangitis in obese mice. Obesity
      exacerbated experimental PSC in part by overproduction of IL-15. Timely targeting
      of IL-15 may slow the progression of PSC.

PMID- 29449575
TI  - Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions
      form the basis of T-PLL.
AB  - T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T
      cell malignancy. Here we integrated large-scale profiling data of alterations in
      gene expression, allelic copy number (CN), and nucleotide sequences in 111 well
      characterized patients. Besides prominent signatures of T-cell activation and
      prevalent clonal variants, we also identify novel hot-spots for CN variability,
      fusion molecules, alternative transcripts, and progression-associated dynamics.
      The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage
      responses, T-cell receptor/cytokine signaling, and histone modulation. We
      formulate a multi-dimensional model of T-PLL pathogenesis centered around a
      unique combination of TCL1 overexpression with damaging ATM aberrations as
      initiating core lesions. The effects imposed by TCL1 cooperate with compromised
      ATM toward a leukemogenic phenotype of impaired DNA damage processing.
      Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and
      telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic
      insults. As non-genotoxic strategies, synergistic combinations of p53
      reactivators and deacetylase inhibitors reinstate such cell death execution.

PMID- 29449579
TI  - Analysis of Epistasis among QTLs on Heading Date based on Single Segment
      Substitution Lines in Rice.
AB  - Heading date directly determines the planting districts and seasons, and thus
      plays an important role for producing and introducing of varieties. Limited to
      the materials and methodologies, analysis of epistasis still presents an obvious
      challenge. This thesis estimated effectively four types of epistatic components
      among dual QTLs on heading date based on eight single segment substitution lines
      (SSSLs) in rice. The results confirmed that they carried truly with heading date
      QTLs. Eleven pairs of QTLs were with 50.0% of significant epistatic effects, of
      which additive-additive, additive-dominance or dominance-additive, and dominance
      dominance interaction components occupied 40.9%, 50.0% and 59.1%, respectively.
      One QTL always interacted with multiple QTLs in various components. Several
      characteristics of epistasis on heading date were found that 1) different
      epistatic components had almost consistent directions; 2) dominance-dominance
      epistasis was perhaps most important in the four epistatic components; 3)
      epistasis was mostly positive, delaying rice heading; and 4) all epistatic
      components were seasonal sensitive. Two flowering pathways were further confirmed
      via a network constructed among these QTLs. These results have further confirmed
      the prevalence of epistatic interactions, deepened the understanding of genetic
      and flowering mechanism, and excavated several advantageous genes on heading date
      in rice.

PMID- 29449580
TI  - Botulinum neurotoxin-encoding plasmids can be conjugatively transferred to
      diverse clostridial strains.
AB  - Most Group I Clostridium botulinum strains harbor botulinum neurotoxin (bont)
      genes on their chromosome, while some carry these genes (including bont/a,
      bont/b, and bont/f) on large plasmids. Prior work in our laboratory demonstrated
      that Group I BoNT plasmids were mobilized to C. botulinum recipient strains
      containing the Tn916 transposon. Here, we show that Tn916 is nonessential for
      plasmid transfer. Relying on an auxotrophic donor phenotype and a plasmid-borne
      selectable marker, we observed the transfer of pCLJ, a 270 kb plasmid harboring
      two bont genes, from its host strain to various clostridia. Transfer frequency
      was greatest to other Group I C. botulinum strains, but the plasmid was also
      transferred into traditionally nontoxigenic species, namely C. sporogenes and C.
      butyricum. Expression and toxicity of BoNT/A4 was confirmed in transconjugants by
      immunoblot and mouse bioassay. These data indicate that conjugation within the
      genus Clostridium can occur across physiological Groups of C. botulinum,
      supporting horizontal gene transfer via bont-bearing plasmids. The transfer of
      plasmids possessing bont genes to resistant Clostridium spp. such as C.
      sporogenes could impact biological safety for animals and humans. These plasmids
      may play an environmental role in initiating death in vertebrates, leading to
      decomposition and nutrient recycling of animal biomass.

PMID- 29449581
TI  - Dyslipidemia and risk of renal replacement therapy or death in incident pre
      dialysis patients.
AB  - Globally the number of patients on renal replacement therapy (RRT) is rising.
      Dyslipidemia is a potential modifiable cardiovascular risk factor, but its effect
      on risk of RRT or death in pre-dialysis patients is unclear. The aim of this
      study was to assess the association between dyslipidemia and risk of RRT or death
      among patients with CKD stage 4-5 receiving specialized pre-dialysis care, an
      often under represented group in clinical trials. Of the 502 incident pre
      dialysis patients (>18 y) in the Dutch PREPARE-2 study, lipid levels were
      available in 284 patients and imputed for the other patients. During follow up
      376 (75%) patients started RRT and 47 (9%) patients died. Dyslipidemia was
      defined as total cholesterol >=5.00 mmol/L, LDL cholesterol >=2.50 mmol/L, HDL
      cholesterol <1.00 mmol/L, HDL/LDL ratio <0.4, or triglycerides (TG) >=2.25
      mmol/L, and was present in 181 patients and absent in 93 patients. After
      multivariable adjustment Cox regression analyses showed a HR (95% CI) for the
      combined endpoint for dyslipidemia of 1.12 (0.85-1.47), and for high LDL of 1.20
      (0.89-1.61). All other HRs were smaller. In conclusion, we did not find an
      association between dyslipidemia or the separate lipid levels and RRT or death in
      CKD patients on specialized pre-dialysis care.

PMID- 29449582
TI  - Use of ELISpot assay to study HBs-specific B cell responses in vaccinated and HBV
      infected humans.
AB  - Hepatitis B surface antibody (HBsAb) plays a critical role in protecting against
      infection of hepatitis B virus (HBV) and were extensively studied in literature.
      At the same time, the status of hepatitis B surface antigen (HBs)-specific B
      cells in both vaccinated and HBV infected people received limited attention. In
      the current study, we adopted a highly specific B-cell Enzyme Linked ImmunoSpot
      (ELISpot) assay to analyze HBs-specific B cells in various clinical settings:
      healthy individuals with the history of HBV vaccination before and after
      receiving an extra HBV vaccine boost, people chronically infected with HBV (CHB)
      in various clinical stages, with or without a particular type anti-viral
      treatment, or whether receiving a dose of HBV vaccine. In all of these cases, B
      cell ELISpot assay was used effectively in enumerating the frequency of HBs
      specific B cells. While the focus of the current report was to establish the
      utility of this assay for HBV research, a number of interesting observations were
      made in this pilot study based on the profiles and dynamics of HBs-specific B
      cells in various conditions. Such information is useful to guide the future work
      in designing novel therapeutic strategies against CHB.

PMID- 29449583
TI  - Mesoporous silica nanocarriers encapsulated antimalarials with high therapeutic
      performance.
AB  - The use of nanocarriers in drug delivery is a breakeven research and has received
      a clarion call in biomedicine globally. Herein, two newly nano-biomaterials: MCM
      41 encapsulated quinine (MCM-41 ? QN) (1) and 3-phenylpropyl silane
      functionalized MCM-41 loaded QN (pMCM-41 ? QN) (2) were synthesized and well
      characterized. 1 and 2 along with our two already reported nano-antimalarial
      drugs (MCM-41 ? ATS) (3) and 3-aminopropyl silane functionalized MCM-41 contained
      ATS (aMCM-41 ? ATS) (4) were screened in vitro for their activity against P.
      falciparium W2 strain, cytotoxicity against BGM cells and in vivo for their
      activity against Plasmodium bergheiNK65. 1 has the highest antimalarial activity
      in vivo against P. berghei NK65, (ED50: < 0.0625 mg/kg body weight) and higher
      mean survival time compared to the other nano biomaterials or unencapsulated
      drugs at doses higher than 0.0625 mg/kg body weight. This encapsulation strategy
      of MCM-41 ? QN (1) stands very useful and effective in delivering the drug to the
      target cells compared to other delivery systems and therefore, this encapsulated
      drug may be considered for rational drug design.

PMID- 29449584
TI  - CRISPR whole-genome screening identifies new necroptosis regulators and RIPK1
      alternative splicing.
AB  - The necroptotic cell death pathway is a key component of human pathogen defense
      that can become aberrantly derepressed during tissue homeostasis to contribute to
      multiple types of tissue damage and disease. While formation of the necrosome
      kinase signaling complex containing RIPK1, RIPK3, and MLKL has been extensively
      characterized, additional mechanisms of its regulation and effector functions
      likely remain to be discovered. We screened 19,883 mouse protein-coding genes by
      CRISPR/Cas9-mediated gene knockout for resistance to cytokine-induced necroptosis
      and identified 112 regulators and mediators of necroptosis, including 59 new
      candidate pathway components with minimal or no effect on cell growth in the
      absence of necroptosis induction. Among these, we further characterized the
      function of PTBP1, an RNA binding protein whose activity is required to maintain
      RIPK1 protein abundance by regulating alternative splice-site selection.

PMID- 29449585
TI  - Electrical coupling between A17 cells enhances reciprocal inhibitory feedback to
      rod bipolar cells.
AB  - A17 amacrine cells are an important part of the scotopic pathway. Their synaptic
      varicosities receive glutamatergic inputs from rod bipolar cells (RBC) and
      release GABA onto the same RBC terminal, forming a reciprocal feedback that
      shapes RBC depolarization. Here, using patch-clamp recordings, we characterized
      electrical coupling between A17 cells of the rat retina and report the presence
      of strongly interconnected and non-coupled A17 cells. In coupled A17 cells,
      evoked currents preferentially flow out of the cell through GJs and cross
      synchronization of presynaptic signals in a pair of A17 cells is correlated to
      their coupling degree. Moreover, we demonstrate that stimulation of one A17 cell
      can induce electrical and calcium transients in neighboring A17 cells, thus
      confirming a functional flow of information through electrical synapses in the
      A17 coupled network. Finally, blocking GJs caused a strong decrease in the
      amplitude of the inhibitory feedback onto RBCs. We therefore propose that
      electrical coupling between A17 cells enhances feedback onto RBCs by
      synchronizing and facilitating GABA release from inhibitory varicosities
      surrounding each RBC axon terminal. GJs between A17 cells are therefore critical
      in shaping the visual flow through the scotopic pathway.

PMID- 29449586
TI  - Seismic waveform simulation for models with fluctuating interfaces.
AB  - The contrast of elastic properties across a subsurface interface imposes a
      dominant influence on the seismic wavefield, which includes transmitted and
      reflected waves from the interface. Therefore, for an accurate waveform
      simulation, it is necessary to have an accurate representation of the subsurface
      interfaces within the numerical model. Accordingly, body-fitted gridding is used
      to partition subsurface models so that the grids coincide well with both the
      irregular surface and fluctuating interfaces of the Earth. However, non
      rectangular meshes inevitably exist across fluctuating interfaces. This non
      orthogonality degrades the accuracy of the waveform simulation when using a
      conventional finite-difference method. Here, we find that a summation-by-parts
      (SBP) finite-difference method can be used for models with non-rectangular meshes
      across fluctuating interfaces, and can achieve desirable simulation accuracy. The
      acute angle of non-rectangular meshes can be relaxed to as low as 47 degrees .
      The cell size rate of change between neighbouring grids can be relaxed to as much
      as 30%. Because the non-orthogonality of grids has a much smaller impact on the
      waveform simulation accuracy, the model discretisation can be relatively flexible
      for fitting fluctuating boundaries within any complex problem. Consequently,
      seismic waveform inversion can explicitly include fluctuating interfaces within a
      subsurface velocity model.

PMID- 29449588
TI  - Spectral features of the tunneling-induced transparency and the Autler-Townes
      doublet and triplet in a triple quantum dot.
AB  - We theoretically investigate the spectral features of tunneling-induced
      transparency (TIT) and Autler-Townes (AT) doublet and triplet in a triple-quantum
      dot system. By analyzing the eigenenergy spectrum of the system Hamiltonian, we
      can discriminate TIT and double TIT from AT doublet and triplet, respectively.
      For the resonant case, the presence of the TIT does not exhibit distinguishable
      anticrossing in the eigenenergy spectrum in the weak-tunneling regime, while the
      occurrence of double anticrossings in the strong-tunneling regime shows that the
      TIT evolves to the AT doublet. For the off-resonance case, the appearance of a
      new detuning-dependent dip in the absorption spectrum leads to double TIT
      behavior in the weak-tunneling regime due to no distinguished anticrossing
      occurring in the eigenenergy spectrum. However, in the strong-tunneling regime, a
      new detuning-dependent dip in the absorption spectrum results in AT triplet owing
      to the presence of triple anticrossings in the eigenenergy spectrum. Our results
      can be applied to quantum measurement and quantum-optics devices in solid
      systems.

PMID- 29449587
TI  - The Mechanisms of Bushen-Yizhi Formula as a Therapeutic Agent against Alzheimer's
      Disease.
AB  - Bushen-Yizhi prescription (BSYZ) has been an effective traditional Chinese
      medicine (TCM) prescription in treating Alzheimer's disease (AD) for hundreds of
      years. However, the underlying mechanisms have not been fully elucidated yet. In
      this work, a systems pharmacology approach was developed to reveal the underlying
      molecular mechanisms of BSYZ in treating AD. First, we obtained 329 candidate
      compounds of BSYZ by in silico ADME/T filter analysis and 138 AD-related targets
      were predicted by our in-house WEGA algorithm via mapping predicted targets into
      AD-related proteins. In addition, we elucidated the mechanisms of BSYZ action on
      AD through multiple network analysis, including compound-target network analysis
      and target-function network analysis. Furthermore, several modules regulated by
      BSYZ were incorporated into AD-related pathways to uncover the therapeutic
      mechanisms of this prescription in AD treatment. Finally, further verification
      experiments also demonstrated the therapeutic effects of BSYZ on cognitive
      dysfunction in APP/PS1 mice, which was possibly via regulating amyloid-beta
      metabolism and suppressing neuronal apoptosis. In conclusion, we provide an
      integrative systems pharmacology approach to illustrate the underlying
      therapeutic mechanisms of BSYZ formula action on AD.

PMID- 29449589
TI  - Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media
      severity in the Junbo mouse model.
AB  - Otitis Media (OM) is characterized by epithelial abnormalities and defects in
      innate immunity in the middle ear (ME). Although, BPIFA1, a member of the BPI
      fold containing family of putative innate defence proteins is abundantly
      expressed by the ME epithelium and SNPs in Bpifa1 have been associated with OM
      susceptibility, its role in the ME is not well characterized. We investigated the
      role of BPIFA1 in protection of the ME and the development of OM using murine
      models. Loss of Bpifa1 did not lead to OM development. However, deletion of
      Bpifa1 in Evi1Jbo/+ mice, a model of chronic OM, caused significant exacerbation
      of OM severity, thickening of the ME mucosa and increased collagen deposition,
      without a significant increase in pro-inflammatory gene expression. Our data
      suggests that BPIFA1 is involved in maintaining homeostasis within the ME under
      steady state conditions and its loss in the presence of inflammation, exacerbates
      epithelial remodelling leading to more severe OM.

PMID- 29449590
TI  - Lateral Force Microscopy of Interfacial Nanobubbles: Friction Reduction and Novel
      Frictional Behavior.
AB  - Atomic force microscopy is used to conduct single-asperity friction measurements
      at a water-graphite interface. Local mapping of the frictional force, which is
      based on the degree of the cantilever twisting, shows nearly friction-free when a
      tip scans over a nanobubble. Surprisingly, apart from being gapless, the
      associated friction loop exhibits a tilt in the cantilever twisting versus the
      tip's lateral displacement with the slope depending on the loading force. The
      sign of the slope reverses at around zero loading force. In addition, the
      measured normal and lateral tip-sample interactions exhibit unison versus tip
      sample separation. Theoretical analysis, based on the balance of forces on the
      tip originated from the capillary force of the nanobubble and the torsion of the
      cantilever, offers quantitative explanations for both the tilted friction loop
      and the unison of force curves. The analysis may well apply in a wider context to
      the lateral force characterization on cap-shaped fluid structures such as liquid
      droplets on a solid substrate. This study further points to a new direction for
      friction reduction between solids in a liquid medium.

PMID- 29449591
TI  - Familial Risks Between Urolithiasis and Cancer.
AB  - Urolithiasis (UL, urinary tract stone disease) has been reported to increase
      subsequent cancers in the urinary tract. Recently, we showed data that
      surveillance bias may be an important confounder in the reported associations. In
      the present approach we want to address the question of possible cancer risk
      posed by UL mechanistically. Both UL and cancer have strong genetic components
      and we hypothesize that familial association between UL and cancer may be
      plausible. We thus assess familial risks between UL and cancer, hoping to find an
      explanation why UL may pose a risk of cancer. UL patients were identified from
      hospital inpatient and outpatient records and they were organized in families
      based on the Multigeneration Register into which also national cancer data were
      linked. Standardized incidence ratios were calculated for cancer in the offspring
      generation when parents were diagnosed with UL, and conversely for UL when
      parents were diagnosed with cancer. Familial risks between UL and cancer were
      generally small and inconsistent providing no convincing support of genetic
      sharing between UL and cancer. However, bladder UL was associated weakly with
      prostate cancer, and ureter and bladder UL were associated with salivary gland
      cancer. Potential mechanisms for these findings are proposed.

PMID- 29449592
TI  - First evidence for a multienzyme complex of lipid biosynthesis pathway enzymes in
      Cunninghamella bainieri.
AB  - Malic enzyme (ME) plays a vital role in determining the extent of lipid
      accumulation in oleaginous fungi being the major provider of NADPH for the
      activity of fatty acid synthase (FAS). We report here the first direct evidence
      of the existence of a lipogenic multienzyme complex (the lipid metabolon)
      involving ME, FAS, ATP: citrate lyase (ACL), acetyl-CoA carboxylase (ACC),
      pyruvate carboxylase (PC) and malate dehydrogenase (MDH) in Cunninghamella
      bainieri 2A1. Cell-free extracts prepared from cells taken in both growth and
      lipid accumulation phases were prepared by protoplasting and subjected to Blue
      Native (BN)-PAGE coupled with liquid chromatography-tandem mass spectrometry (LC
      MS/MS). A high molecular mass complex (approx. 3.2 MDa) consisting of the above
      enzymes was detected during lipid accumulation phase indicating positive evidence
      of multienzyme complex formation. The complex was not detected in cells during
      the balanced phase of growth or when lipid accumulation ceased, suggesting that
      it was transiently formed only during lipogenesis.

PMID- 29449593
TI  - Hemopexin is required for adult neurogenesis in the subventricular zone/olfactory
      bulb pathway.
AB  - The neural stem cells (NSCs) of the subventricular zone (SVZ) reside within a
      specialized niche critical for neurogenesis. Hemopexin, a plasma glycoprotein,
      has been extensively studied as a heme scavenger at the systemic level. However,
      little is known about its function in the central nervous system, especially in
      neurogenesis. In the present study, we demonstrate that deletion of hemopexin
      leads to neurogenic abnormalities in the SVZ/olfactory bulb (OB) pathway. The
      lateral ventricle is enlarged in hemopexin-deficient mice, and more apoptosis was
      observed in Dcx+ cells. Lineage differentiation of NSCs was also inhibited in the
      SVZ of hemopexin-deficient mice, with more stem cells stayed in an
      undifferentiated, GFAP+ radial glia-like cell stage. Moreover, hemopexin deletion
      resulted in impaired neuroblast migration in the rostral migratory stream.
      Furthermore, exogenous hemopexin protein inhibited apoptosis and promoted the
      migration and differentiation of cultured NSCs. Finally, immunohistochemical
      analysis demonstrated that deletion of hemopexin reduced the number of
      interneurons in the OB. Together, these results suggest a new molecular mechanism
      for the NSC niche that regulates adult neurogenesis in the SVZ/OB pathway. Our
      findings may benefit the understanding for olfactory system development.

PMID- 29449594
TI  - Rapid identification of a stripe rust resistant gene in a space-induced wheat
      mutant using specific locus amplified fragment (SLAF) sequencing.
AB  - Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the
      most devastating diseases of wheat. Resistant cultivars are the preferred
      strategy to control the disease. Space-induced wheat mutant R39 has adult-plant
      resistance (APR) to Pst. Genetic analysis indicated that a single recessive gene,
      designated YrR39, was responsible for the APR of R39 to Pst. Bulked segregant
      analysis (BSA) combined with a SLAF sequencing (SLAF-seq) strategy was used to
      fine-map YrR39 to a 17.39 Mb segment on chromosome 4B. The region was confirmed
      by analysis with simple sequence repeat (SSR) markers. A total of 126 genes were
      annotated in the region and 21 genes with annotations associated with disease
      response were selected for further qRT-PCR analysis. The candidate gene
      Traes_4BS_C868349E1 (annotated as an F-box/LRR-repeat protein) was up-regulated
      after 12, 24, 48, and 96 hours post inoculation with Pst, suggesting it is likely
      involved in the resistance. The current study demonstrated that BSA combined with
      SLAF-seq for SNP discovery is an efficient approach for mapping and identifying
      candidate functional gene.

PMID- 29449595
TI  - Temporal Differentiation of Crop Growth as One of the Drivers of Intercropping
      Yield Advantage.
AB  - Intercropping studies usually focus on yield advantage and interspecific
      interactions but few quantify temporal niche differentiation and its relationship
      with intercropping yield advantage. A field experiment conducted in northwest
      China in 2013 and 2014 examined four intercropping systems (oilseed rape/maize,
      oilseed rape/soybean, potato/maize, and soybean/potato) and the corresponding
      monocultures. Total dry matter data collected every 20 d after maize emergence
      were fitted to logistic models to investigate the temporal dynamics of crop
      growth and interspecific interactions. All four intercropping systems showed
      significant yield advantages. Temporal niche complementarity between intercropped
      species was due to differences in sowing and harvesting dates or the time taken
      to reach maximum daily growth rate or both. Interspecific interactions between
      intercropped species amplified temporal niche differentiation as indicated by
      postponement of the time taken to reach maximum daily growth rate of late
      maturing crops (i.e. 21 to 41 days in maize associated with oilseed rape or
      potato). Growth trajectories of intercropped maize or soybean recovered after the
      oilseed rape harvest to the same values as in their monoculture on a per plant
      basis. Amplified niche differentiation between crop species depends on the
      identity of neighboring species whose relative growth rate is crucial in
      determining the differentiation.

PMID- 29449596
TI  - Heparan sulfates facilitate harmless amyloidogenic fibril formation interacting
      with elastin-like peptides.
AB  - Heparan sulfates (HSs) modulate tissue elasticity in physiopathological
      conditions by interacting with various matrix constituents as tropoelastin and
      elastin-derived peptides. HSs bind also to protein moieties accelerating amyloid
      formation and influencing cytotoxic properties of insoluble fibrils.
      Interestingly, amyloidogenic polypeptides, despite their supposed pathogenic
      role, have been recently explored as promising bio-nanomaterials due to their
      unique and interesting properties. Therefore, we investigated the interactions of
      HSs, obtained from different sources and exhibiting various degree of sulfation,
      with synthetic amyloidogenic elastin-like peptides (ELPs), also looking at the
      effects of these interactions on cell viability and cell behavior using in vitro
      cultured fibroblasts, as a prototype of mesenchymal cells known to modulate the
      soft connective tissue environment. Results demonstrate, for the first time, that
      HSs, with differences depending on their sulfation pattern and chain length,
      interact with ELPs accelerating aggregation kinetics and amyloid-like fibril
      formation as well as self-association. Furthermore, these fibrils do not
      negatively affect fibroblasts' cell growth and parameters of redox balance, and
      influence cellular adhesion properties. Data provide information for a better
      understanding of the interactions altering the elastic component in aging and in
      pathologic conditions and may pave the way for the development of composite
      matrix-based biomaterials.

PMID- 29449597
TI  - Substructure-activity relationship studies on antibody recognition for phenylurea
      compounds using competitive immunoassay and computational chemistry.
AB  - Based on the structural features of fluometuron, an immunizing hapten was
      synthesized and conjugated to bovine serum albumin as an immunogen to prepare a
      polyclonal antibody. However, the resultant antibody indicated cross-reactivity
      with 6 structurally similar phenylurea herbicides, with binding activities
      (expressed by IC50 values) ranging from 1.67 ug/L to 42.71 ug/L. All 6 phenylurea
      herbicides contain a common moiety and three different substitutes. To understand
      how these three different chemical groups affect the antibody-phenylurea
      recognition activity, quantum chemistry, using density function theory (DFT) at
      the B3LYP/6-311++ G(d,p) level of theory, was employed to optimize all phenylurea
      structures, followed by determination of the 3D conformations of these molecules,
      pharmacophore analysis, and molecular electrostatic potential (ESP) analysis. The
      molecular modeling results confirmed that the geometry configuration,
      pharmacophore features and electron distribution in the substituents were related
      to the antibody binding activity. Spearman correlation analysis further
      elucidated that the geometrical and electrostatic properties on the van der Waals
      (vdW) surface of the substituents played a critical role in the antibody
      phenylurea recognition process.

PMID- 29449598
TI  - Health-related quality of life in adolescents and the retinal microvascular
      structure.
AB  - We aimed to investigate whether health-related quality of life (HRQoL) is
      associated with retinal vascular caliber, an indicator of subclinical
      cardiovascular disease risk. 1600 students aged between 11-19 years (821 girls
      and 779 boys) were examined during 2009-2011. Retinal vessel caliber was measured
      from digital retinal images. HRQoL was assessed by the Pediatric Quality of Life
      Inventory (PedsQL). In the overall cohort, each 1-unit increase in PedsQL total
      score and the psychosocial summary score was associated with ~0.05 MUm narrowing
      in retinal arteriolar caliber (multivariable-adjusted p-value = 0.01).
      Participants in the lowest versus highest tertile of PedsQL total score,
      psychosocial summary, social and school item scores had significantly wider
      retinal arteriolar caliber: 161.7 MUm versus 160.2 MUm (p = 0.02); 161.6 MUm
      versus 160.0 MUm (p = 0.02); 161.6 MUm versus 159.9 MUm (p = 0.002); and 161.6
      MUm versus 159.9 MUm (p = 0.01), respectively. Significant interactions (p <
      0.05) were observed between gender and PedsQL total score with retinal arteriolar
      calibre. In boys, inverse associations were observed between PedsQL total score
      (p = 0.01), psychosocial summary (p = 0.01), and social scores (p = 0.01) and
      retinal arteriolar caliber. No significant associations were observed between
      PedsQL scores and retinal vessel caliber in girls. Diminished HRQoL in
      adolescents was independently associated with structural retinal microvascular
      changes.

PMID- 29449599
TI  - Red blood cells are dynamic reservoirs of cytokines.
AB  - Red blood cells (RBCs) have been shown to affect immune function and can induce
      inflammatory responses after transfusion. The transfusion of washed RBCs can
      significantly reduce adverse effects, however, the soluble factors that may
      mediate these effects have not been identified. Previous studies have identified,
      but not quantified, a small number of chemokines associated with RBCs. We
      isolated RBCs from healthy volunteers and quantified of a panel of 48 cytokines,
      chemokines, and growth factors in the lysate, cytosol, and conditioned media of
      these cells using Luminex(r) technology. This analysis revealed that, after
      correcting for white blood cell and platelet contamination, 46 cytokines were
      detected in RBC lysates, and the median concentration in RBCs was 12-fold higher
      than in the plasma. In addition, extensive washing of RBCs, such as that
      performed in proteomics analyses or prior to some RBC transfusions, significantly
      attenuated the release of six cytokines following incubation at 37  degrees C.
      This supports the hypothesis that, alongside its gas exchange function, RBCs play
      a role in cytokine signalling. This discovery may help supplement disease
      biomarker research and may shed light on adverse inflammatory processes that can
      follow RBC transfusion.

PMID- 29449601
TI  - Solar Thermo-coupled Electrochemical Oxidation of Aniline in Wastewater for the
      Complete Mineralization Beyond an Anodic Passivation Film.
AB  - Herein, we report the solar thermal electrochemical process (STEP) aniline
      oxidation in wastewater for totally solving the two key obstacles of the huge
      energy consumption and passivation film in the electrochemical treatment. The
      process, fully driven by solar energy without input of any other energies,
      sustainably serves as an efficient thermoelectrochemical oxidation of aniline by
      the control of the thermochemical and electrochemical coordination. The
      thermocoupled electrochemical oxidation of aniline achieved a fast rate and high
      efficiency for the full minimization of aniline to CO2 with the stability of the
      electrode and without formation of polyaniline (PAN) passivation film. A clear
      mechanism of aniline oxidation indicated a switching of the reactive pathway by
      the STEP process. Due to the coupling of solar thermochemistry and
      electrochemistry, the electrochemical current remained stable, significantly
      improving the oxidation efficiency and mineralization rate by apparently
      decreasing the electrolytic potential when applied with high temperature. The
      oxidation rate of aniline and chemical oxygen demand (COD) removal rate could be
      lifted up to 2.03 and 2.47 times magnification compared to conventional
      electrolysis, respectively. We demonstrate that solar-driven STEP processes are
      capable of completely mineralizing aniline with high utilization of solar energy.
      STEP aniline oxidation can be utilized as a green, sustainable water treatment.

PMID- 29449600
TI  - Glucocorticoids promote apoptosis of proinflammatory monocytes by inhibiting ERK
      activity.
AB  - Glucocorticoids (GCs) are potent anti-inflammatory drugs whose mode of action is
      complex and still debatable. One likely cellular target of GCs are
      monocytes/macrophages. The role of GCs in monocyte survival is also debated.
      Although both granulocyte macrophage-colony stimulating factor (GM-CSF) and
      macrophage-CSF (M-CSF) are important regulators of macrophage lineage functions
      including their survival, the former is often associated with proinflammatory
      functions while the latter is important in lineage homeostasis. We report here
      that the GC, dexamethasone, induces apoptosis in GM-CSF-treated human monocytes
      while having no impact on M-CSF-induced monocyte survival. To understand how GCs,
      GM-CSF, and M-CSF are regulating monocyte survival and other functions during
      inflammation, we firstly examined the transcriptomic changes elicited by these
      three agents in human monocytes, either acting alone or in combination.
      Transcriptomic and Ingenuity pathway analyses found that dexamethasone
      differentially modulated dendritic cell maturation and TREM1 signaling pathways
      in GM-CSF-treated and M-CSF-treated monocytes, two pathways known to be regulated
      by ERK1/2 activity. These analyses led us to provide evidence that the GC
      inhibits ERK1/2 activity selectively in GM-CSF-treated monocytes to induce
      apoptosis. It is proposed that this inhibition of ERK1/2 activity leads to
      inactivation of p90 ribosomal-S6 kinase and Bad dephosphorylation leading in turn
      to enhanced caspase-3 activity and subsequent apoptosis. Furthermore,
      pharmacological inhibition of GC receptor activity restored the ERK1/2 signaling
      and prevented the GC-induced apoptosis in GM-CSF-treated monocytes. Increased
      tissue macrophage numbers, possibly from enhanced survival due to mediators such
      as GM-CSF, can correlate with inflammatory disease severity; also reduction in
      these numbers can correlate with the therapeutic benefit of a number of agents,
      including GCs. We propose that the ERK1/2 signaling pathway promotes survival of
      GM-CSF-treated proinflammatory monocytes, which can be selectively targeted by
      GCs as a novel mechanism to reduce local monocyte/macrophage numbers and hence
      inflammation.

PMID- 29449602
TI  - Diamond FinFET without Hydrogen Termination.
AB  - In this letter we report the first diamond fin field-effect transistor (diamond
      FinFET) without a hydrogen-terminated channel. The device operates with hole
      accumulation by metal-oxide-semiconductor (MOS) structures built on fins to
      maintain effective control of the channel conduction. Devices with 100-nm-wide
      fins were designed and fabricated to ensure that the channel pinched off at zero
      gate bias. The transfer characteristic of FinFET showed a greater than 3000
      on/off ratio, successfully demonstrating the transistor behavior. Devices were
      characterized at room temperature and at 150  degrees C, showing 30 mA/mm current
      density at 150  degrees C, 35 times more than current density at room
      temperature. The diamond FinFET, which leverages the fin concept from the silicon
      industry and the material advance of diamond, enables a new class of diamond
      transistors for applications from digital to power and radio frequency (RF)
      electronics.

PMID- 29449603
TI  - Cinacalcet versus Placebo for secondary hyperparathyroidism in chronic kidney
      disease patients: a meta-analysis of randomized controlled trials and trial
      sequential analysis.
AB  - To assess the efficacy and safety of cinacalcet on secondary hyperparathyroidism
      in patients with chronic kidney disease, Pubmed, Embase, and the Cochrane Central
      Register of Controlled Trials were searched until March 2016. Trial sequential
      analysis (TSA) was conducted to control the risks of type I and II errors and
      calculate required information size (RIS). A total of 25 articles with 8481
      participants were included. Compared with controls, cinacalcet administration did
      not reduce all-cause mortality (RR = 0.97, 95% CI = 0.89-1.05, P = 0.41, TSA
      adjusted 95% CI = 0.86-1.08, RIS = 5260, n = 8386) or cardiovascular mortality
      (RR = 0.95, 95% CI = 0.83-1.07, P = 0.39, TSA-adjusted 95% CI = 0.70-1.26, RIS =
      3780 n = 5418), but it reduced the incidence of parathyroidectomy (RR = 0.48, 95%
      CI = 0.40-0.50, P < 0.001, TSA-adjusted 95% CI = 0.39-0.60, RIS = 5787 n = 5488).
      Cinacalcet increased the risk of hypocalcemia (RR = 8.48, 95% CI = 6.37-11.29, P
      < 0.001, TSA-adjusted 95% CI = 5.25-13.70, RIS = 6522, n = 7785), nausea (RR =
      2.12, 95% CI = 1.62-2.77, P < 0.001, TSA-adjusted 95% CI = 1.45-3.04, RIS = 4684,
      n = 7512), vomiting (RR = 2.00, 95% CI = 1.79-2.24, P < 0.001, TSA-adjusted 95%
      CI = 1.77-2.26, RIS = 1374, n = 7331) and diarrhea (RR = 1.17, 95% CI = 1.05
      1.32, P = 0.006, TSA-adjusted 95% CI = 1.02-1.36, RIS = 8388, n = 6116).
      Cinacalcet did not significantly reduce the incidence of fractures (RR = 0.58,
      95% CI = 0.21-1.59, P = 0.29, TSA-adjusted 95% CI = 0.01-35.11, RIS = 76376, n =
      4053). Cinacalcet reduced the incidence of parathyroidectomy, however, it did not
      reduce all-cause and cardiovascular mortality, and increased the risk of adverse
      events including hypocalcemia and gastrointestinal disorders.

PMID- 29449604
TI  - Intravenous synthetic platelet (SynthoPlate) nanoconstructs reduce bleeding and
      improve 'golden hour' survival in a porcine model of traumatic arterial
      hemorrhage.
AB  - Traumatic non-compressible hemorrhage is a leading cause of civilian and military
      mortality and its treatment requires massive transfusion of blood components,
      especially platelets. However, in austere civilian and battlefield locations,
      access to platelets is highly challenging due to limited supply and portability,
      high risk of bacterial contamination and short shelf-life. To resolve this, we
      have developed an I.V.-administrable 'synthetic platelet' nanoconstruct
      (SynthoPlate), that can mimic and amplify body's natural hemostatic mechanisms
      specifically at the bleeding site while maintaining systemic safety. Previously
      we have reported the detailed biochemical and hemostatic characterization of
      SynthoPlate in a non-trauma tail-bleeding model in mice. Building on this, here
      we sought to evaluate the hemostatic ability of SynthoPlate in emergency
      administration within the 'golden hour' following traumatic hemorrhagic injury in
      the femoral artery, in a pig model. We first characterized the storage stability
      and post-sterilization biofunctionality of SynthoPlate in vitro. The
      nanoconstructs were then I.V.-administered to pigs and their systemic safety and
      biodistribution were characterized. Subsequently we demonstrated that, following
      femoral artery injury, bolus administration of SynthoPlate could reduce blood
      loss, stabilize blood pressure and significantly improve survival. Our results
      indicate substantial promise of SynthoPlate as a viable platelet surrogate for
      emergency management of traumatic bleeding.

PMID- 29449605
TI  - Image Transport Through Meter-Long Randomly Disordered Silica-Air Optical Fiber.
AB  - We present a randomly disordered silica-air optical fiber featuring a 28.5% air
      filling fraction in the structured region, and low attenuation below 1 dB per
      meter at visible wavelengths. The quality of images transported through this
      fiber is shown to be comparable to, or even better than, that of images sent
      through commercial multicore imaging fiber. We demonstrate robust high-quality
      optical image transfer through 90 cm-long fibers with disordered silica-air
      structure, more than an order of magnitude improvement compared to previous
      disordered fiber imaging distances. The effects of variations of wavelength and
      feature size on transported image quality are investigated experimentally.

PMID- 29449606
TI  - Human subarachnoid space width oscillations in the resting state.
AB  - Abnormal cerebrospinal fluid (CSF) pulsatility has been implicated in patients
      suffering from various diseases, including multiple sclerosis and hypertension.
      CSF pulsatility results in subarachnoid space (SAS) width changes, which can be
      measured with near-infrared transillumination backscattering sounding (NIR
      T/BSS). The aim of this study was to combine NIR-T/BSS and wavelet analysis
      methods to characterise the dynamics of the SAS width within a wide range of
      frequencies from 0.005 to 2 Hz, with low frequencies studied in detail for the
      first time. From recordings in the resting state, we also demonstrate the
      relationships between SAS width in both hemispheres of the brain, and investigate
      how the SAS width dynamics is related to the blood pressure (BP). These
      investigations also revealed influences of age and SAS correlation on the
      dynamics of SAS width and its similarity with the BP. Combination of NIR-T/BSS
      and time-frequency analysis may open up new frontiers in the understanding and
      diagnosis of various neurodegenerative and ageing related diseases to improve
      diagnostic procedures and patient prognosis.

PMID- 29449607
TI  - 6-Thioguanine is a noncompetitive and slow binding inhibitor of human
      deubiquitinating protease USP2.
AB  - Ubiquitin-specific protease 2 (USP2) belongs to the family of deubiquitinases
      that can rescue protein targets from proteasomal degradation by reversing their
      ubiquitination. In various cancers, including prostate cancer and ovarian
      carcinoma, upregulation of USP2 leads to an increase in the levels of
      deubiquitinated substrates such as fatty acid synthase, MDM2, cyclin D1 and
      Aurora-A. USP2 thus plays a critical role in tumor cells' survival and therefore
      represents a therapeutic target. Here a leukemia drug, 6-thioguanine, was found
      to be a potent inhibitor of USP2. Enzyme-kinetic and X-ray crystallographic data
      suggest that 6-thioguanine displays a noncompetitive and slow-binding inhibitory
      mechanism against USP2. Our study provides a clear rationale for the clinical
      evaluation of 6-thioguanine for USP2-upregulated cancers.

PMID- 29449608
TI  - Mapping molecular assemblies with fluorescence microscopy and object-based
      spatial statistics.
AB  - Elucidating protein functions and molecular organisation requires to localise
      precisely single or aggregated molecules and analyse their spatial distributions.
      We develop a statistical method SODA (Statistical Object Distance Analysis) that
      uses either micro- or nanoscopy to significantly improve on standard co
      localisation techniques. Our method considers cellular geometry and densities of
      molecules to provide statistical maps of isolated and associated (coupled)
      molecules. We use SODA with three-colour structured-illumination microscopy (SIM)
      images of hippocampal neurons, and statistically characterise spatial
      organisation of thousands of synapses. We show that presynaptic synapsin is
      arranged in asymmetric triangle with the 2 postsynaptic markers homer and PSD95,
      indicating a deeper localisation of homer. We then determine stoichiometry and
      distance between localisations of two synaptic vesicle proteins with 3D-STORM.
      These findings give insights into the protein organisation at the synapse, and
      prove the efficiency of SODA to quantitatively assess the geometry of molecular
      assemblies.

PMID- 29449609
TI  - Kinesthetic stimulation for obstructive sleep apnea syndrome: An "on-off" proof
      of concept trial.
AB  - Obstructive sleep apnea (OSA) occurs when the upper airway narrows or collapses
      due to the loss of upper airway muscle activation at sleep onset. This study
      investigated the effectiveness of triggered kinesthetic stimulation in patients
      with OSA. This proof-of-concept, open-label, multicenter prospective study was
      conducted on 24 patients with severe OSA. During a one night evaluation,
      kinesthetic stimulation was intermittently delivered in 30 minute periods. The
      duration of apneas and hypopneas during Stim on and Stim off periods were
      compared. Five hospital-based university centers in France participated. Sleep
      studies were evaluated by a single scorer at a core laboratory (CHU Grenoble).
      Results show that during the Stim on phases, statistically significant decreases
      in durations of apneas and hypopneas were observed in 56% and 46% of patients,
      respectively. Overall, 75% of patients showed an improvement in apneas or
      hypopneas durations. The mean reduction in durations for patients with a
      significant decrease was 4.86 seconds for apneas and 6.00 seconds for hypopneas.
      This proof of concept study is the first to identify kinesthetic stimulation as a
      potentially effective therapy for OSA. These data justify evaluation in a
      controlled study.

PMID- 29449610
TI  - Phaeophleospora vochysiae Savi & Glienke sp. nov. Isolated from Vochysia
      divergens Found in the Pantanal, Brazil, Produces Bioactive Secondary
      Metabolites.
AB  - Microorganisms associated with plants are highly diverse and can produce a large
      number of secondary metabolites, with antimicrobial, anti-parasitic and cytotoxic
      activities. We are particularly interested in exploring endophytes from medicinal
      plants found in the Pantanal, a unique and widely unexplored wetland in Brazil.
      In a bio-prospecting study, strains LGMF1213 and LGMF1215 were isolated as
      endophytes from Vochysia divergens, and by morphological and molecular
      phylogenetic analyses were characterized as Phaeophleospora vochysiae sp. nov.
      The chemical assessment of this species reveals three major compounds with high
      biological activity, cercoscosporin (1), isocercosporin (2) and the new compound
      3-(sec-butyl)-6-ethyl-4,5-dihydroxy-2-methoxy-6-methylcyclohex-2-enone (3).
      Besides the isolation of P. vochysiae as endophyte, the production of cercosporin
      compounds suggest that under specific conditions this species causes leaf spots,
      and may turn into a pathogen, since leaf spots are commonly caused by species of
      Cercospora that produce related compounds. In addition, the new compound 3-(sec
      butyl)-6-ethyl-4,5-dihydroxy-2-methoxy-6-methylcyclohex-2-enone showed
      considerable antimicrobial activity and low cytotoxicity, which needs further
      exploration.

PMID- 29449611
TI  - Seasonal resource conditions favor a summertime increase in North Pacific diatom
      diazotroph associations.
AB  - In the North Pacific Subtropical Gyre (NPSG), an annual pulse of sinking organic
      carbon is observed at 4000 m between July and August, driven by large diatoms
      found in association with nitrogen fixing, heterocystous, cyanobacteria: Diatom
      Diazotroph Associations (DDAs). Here we ask what drives the bloom of DDAs and
      present a simplified trait-based model of subtropical phototroph populations
      driven by observed, monthly averaged, environmental characteristics. The ratio of
      resource supply rates favors nitrogen fixation year round. The relative fitness
      of DDA traits is most competitive in early summer when the mixed layer is
      shallow, solar irradiance is high, and phosphorus and iron are relatively
      abundant. Later in the season, as light intensity drops and phosphorus is
      depleted, the traits of small unicellular diazotrophs become more competitive.
      The competitive transition happens in August, at the time when the DDA export
      event occurs. This seasonal dynamic is maintained when embedded in a more
      complex, global-scale, ecological model, and provides predictions for the extent
      of the North Pacific DDA bloom. The model provides a parsimonious and testable
      hypothesis for the stimulation of DDA blooms.

PMID- 29449613
TI  - Health-care spending and utilization for children discharged from a neonatal
      intensive care unit.
AB  - OBJECTIVES: To describe health-care spending and utilization for infants
      discharged from the neonatal intensive care unit (NICU). STUDY DESIGN:
      Retrospective cohort analysis of 4973 NICU graduates in the Truven MarketScan
      Medicaid database, with follow-up to the third birthday. Health-care spending and
      utilization after NICU discharge were assessed. Using logistic regression, we
      assessed clinical characteristics associated with hospitalization and emergency
      department (ED) visits. RESULTS: Most (69.5%) post-NICU spending occurred within
      the first year [$33,276 per member per year]. Inpatient care accounted for most
      (71.6%) of the 3-year spending. The percentages of infants with a 1-year
      readmission or ED visit were 36.8% and 63.7%, respectively. Medical technology
      was associated with the highest likelihoods of hospital [aOR 17.8 (95%CI 12.2
      26.0)] and ED use [aOR 2.3 (95%CI 1.8-3.0)]. CONCLUSIONS: Hospital care accounts
      for the majority of spending for NICU graduates. Infants with medical technology
      have the highest risk of hospital and ED use.

PMID- 29449612
TI  - Ixr1 Regulates Ribosomal Gene Transcription and Yeast Response to Cisplatin.
AB  - Ixr1 is a Saccharomyces cerevisiae HMGB protein that regulates the hypoxic
      regulon and also controls the expression of other genes involved in the oxidative
      stress response or re-adaptation of catabolic and anabolic fluxes when oxygen is
      limiting. Ixr1 also binds with high affinity to cisplatin-DNA adducts and
      modulates DNA repair. The influence of Ixr1 on transcription in the absence or
      presence of cisplatin has been analyzed in this work. Ixr1 regulates other
      transcriptional factors that respond to nutrient availability or extracellular
      and intracellular stress stimuli, some controlled by the TOR pathway and PKA
      signaling. Ixr1 controls transcription of ribosomal RNAs and genes encoding
      ribosomal proteins or involved in ribosome assembly. qPCR, ChIP, and 18S and 25S
      rRNAs measurement have confirmed this function. Ixr1 binds directly to several
      promoters of genes related to rRNA transcription and ribosome biogenesis.
      Cisplatin treatment mimics the effect of IXR1 deletion on rRNA and ribosomal gene
      transcription, and prevents Ixr1 binding to specific promoters related to these
      processes.

PMID- 29449614
TI  - Decreased succinate dehydrogenase B in human hepatocellular carcinoma accelerates
      tumor malignancy by inducing the Warburg effect.
AB  - Changes in TCA cycle enzymes or respiratory activity are possible mechanisms of
      aerobic glycolysis that contributes to tumor progression. To clarify whether the
      decrease of succinate dehydrogenase B (SDHB) alters energy metabolism, induces
      the Warburg effect and results in tumor malignancy, SDHB expression was examined
      and modulated in hepatocellular carcinoma (HCC) tissues and cells, respectively.
      SDHB level was often decreased in malignant HCC cells and tissues. Furthermore,
      the reduced SDHB expression was associated with advanced tumor stage and poor
      survival rate. Moreover, silencing of SDHB altered energy metabolism switched
      from aerobic respiration to glycolysis, resulted in the Warburg effect, and
      enhanced cell proliferation and motility. In contrast, the SDHB overexpression
      deregulated bioenergetic metabolism and decreased cell growth and migration. In
      mouse xenograft models, subcutaneous implantation and tail vein injection with
      SDHB knockdown cells resulted in a larger tumor volume and accelerated cancer
      metastasis, respectively. A mutation or decrease in SDHB induced the switch from
      aerobic respiration to glycolysis. This metabolic alteration was associated with
      tumor cell dedifferentiation, proliferation, motility and overall patient
      survival in HCC.

PMID- 29449616
TI  - Big double bubble trouble: in vivo real time demonstration of 'mixed-type bubble'
      and its consequent effects during deep anterior lamellar keratoplasty.

PMID- 29449615
TI  - Improved retinal and visual function following panmacular subthreshold diode
      micropulse laser for retinitis pigmentosa.
AB  - OBJECTIVES: To examine the effect of subthreshold diode micropulse laser (SDM) on
      pattern electroretinography (PERG) and visual function in retinitis pigmentosa
      (RP). METHODS: The records of all patients (pts) undergoing SDM in a
      vitreoretinal subspecialty practice were reviewed. Inclusion criteria included
      the presence of RP evaluated before and after SDM by PERG. As a secondary outcome
      measure, the results of automated omnifield resolution perimetry (ORP) were also
      reviewed. RESULTS: All eyes undergoing SDM for RP were eligible study, including
      26 eyes of 15 pts; seven male and eight female, aged 16-69 (avg. 47) years.
      Retinal function by PERG improved by all indices, with significant improvements
      in the 24 degrees  field signal latency measures; the MagD(uV)/ Mag(uV) ratio (P
      < 0.0001) and the MagD(uV) amplitude (P = 0.0003). ORP significantly improved by
      all indices (p = 0.02-0.002). Average best-corrected chart visual acuities
      improved from 0.6 to 0.4 logMAR units (p = 0.02). There were no adverse treatment
      effects. CONCLUSIONS: SDM significantly improved chart visual acuity, mesopic
      logMAR visual acuity perimetry, and retinal function by PERG in RP without
      adverse treatment effects. Treatment responses indicate a significant capacity
      for rescue of dysfunctional retina. These results suggest that early and periodic
      treatment with SDM might slow disease progression and reduce long-term vision
      loss.

PMID- 29449617
TI  - Publisher Correction: Affinity purification of cell-specific mitochondria from
      whole animals resolves patterns of genetic mosaicism.
AB  - In the version of this Technical Report originally published, chromosome
      representations (indicated by black lines) were missing from Fig. 2a due to a
      technical error. The corrected version of Fig. 2a is shown below. This has now
      been amended in all online versions of the Technical Report.

PMID- 29449618
TI  - Codon based co-occurrence network motifs in human mitochondria.
AB  - The nucleotide polymorphism in the human mitochondrial genome (mtDNA) tolled by
      codon position bias plays an indispensable role in human population dispersion
      and expansion. Herein, genome-wide nucleotide co-occurrence networks were
      constructed using data comprised of five different geographical regions and
      around 3000 samples for each region. We developed a powerful network model to
      describe complex mitochondrial evolutionary patterns among codon and non-codon
      positions. We found evidence that the evolution of human mitochondria DNA is
      dominated by adaptive forces, particularly mutation and selection, which was
      supported by many previous studies. The diversity observed in the mtDNA was
      compared with mutations, co-occurring mutations, network motifs considering codon
      positions as causing agent. This comparison showed that long-range nucleotide co
      occurrences have a large effect on genomic diversity. Most notably, codon motifs
      apparently underpinned the preferences among codon positions for co-evolution
      which is probably highly biased during the origin of the genetic code. Our
      analysis also showed that variable nucleotide positions of different human sub
      populations implemented the independent mtDNA evolution to its geographical
      dispensation. Ergo, this study has provided both a network framework and a codon
      glance to investigate co-occurring genomic variations that are critical in
      underlying complex mitochondrial evolution.

PMID- 29449619
TI  - Chronic ETA antagonist reverses hypertension and impairment of structure and
      function of peripheral small arteries in aortic stiffening.
AB  - Arterial stiffness may contribute to the pathogenesis of hypertension. The goal
      of this study is to elucidate the role of Endothelin-1 (ET-1) in aortic
      stiffening-induced hypertension through ETA receptor activation. An increase in
      aortic stiffness was created by use of a non-constrictive restraint, NCR on the
      abdominal aortic surface. A group of rats underwent aortic NCR or sham operation
      for 12 weeks and were then treated with ETA receptor antagonist BQ-123 for 3
      weeks. We found that 12 weeks of aortic NCR significantly increased pulse and
      mean pressure and altered peripheral flow pattern, accompanied by an increased
      serum ET-1 level (p < 0.05). The increase in aortic stiffness (evidenced by an
      elevated pulse wave velocity) caused hypertrophic structural remodeling and
      decreased arterial compliance, along with an impaired endothelial function in
      peripheral small arteries. BQ-123 treatment only partially attenuated peripheral
      arterial hypertrophy and restored arterial compliance, but completely recovered
      endothelium function, and consequently restored local flow and lowered blood
      pressure. Our findings underscore the hemodynamic coupling between aortic
      stiffening and peripheral arterial vessels and flow dynamics through an ETA
      dependent mechanism. ETA receptor blockade may have therapeutic potential for
      improving peripheral vessel structure and function in the treatment of aortic
      stiffness-induced hypertension.

PMID- 29449620
TI  - Ultra-Broadband Optical Gain in III-Nitride Digital Alloys.
AB  - A novel III-Nitride digital alloy (DA) with ultra-broadband optical gain is
      proposed. Numerical analysis shows a 50-period InN/GaN DA yields minibands that
      are densely quantized by numerous confined states. Interband transitions between
      the conduction and valence minibands create ultra-broadband optical gain spectra
      with bandwidths up to ~1 MUm that can be tuned from the red to infrared. In
      addition, the ultra-broadband optical gain, bandwidth, and spectral coverage of
      the III-Nitride DA is very sensitive to layer thickness and other structural
      design parameters. This study shows the promising potential of the III-Nitride
      DAs with tunable ultra-broadband interband optical gain for use in semiconductor
      optical amplifiers and future III-Nitride photonic integration applications.

PMID- 29449621
TI  - Polygonum aviculare L. extract and quercetin attenuate contraction in airway
      smooth muscle.
AB  - Because of the serious side effects of the currently used bronchodilators, new
      compounds with similar functions must be developed. We screened several herbs and
      found that Polygonum aviculare L. contains ingredients that inhibit the
      precontraction of mouse and human airway smooth muscle (ASM). High K+-induced
      precontraction in ASM was completely inhibited by nifedipine, a selective blocker
      of L-type voltage-dependent Ca2+ channels (LVDCCs). However, nifedipine only
      partially reduced the precontraction induced by acetylcholine chloride (ACH).
      Additionally, the ACH-induced precontraction was partly reduced by pyrazole-3
      (Pyr3), a selective blocker of TRPC3 and stromal interaction molecule (STIM)/Orai
      channels. These channel-mediated currents were inhibited by the compounds present
      in P. aviculare extracts, suggesting that this inhibition was mediated by LVDCCs,
      TRPC3 and/or STIM/Orai channels. Moreover, these channel-mediated currents were
      inhibited by quercetin, which is present in P. aviculare extracts. Furthermore,
      quercetin inhibited ACH-induced precontraction in ASM. Overall, our data indicate
      that the ethyl acetate fraction of P. aviculare and quercetin can inhibit Ca2+
      permeant LVDCCs, TRPC3 and STIM/Orai channels, which inhibits the precontraction
      of ASM. These findings suggest that P. aviculare could be used to develop new
      bronchodilators to treat obstructive lung diseases such as asthma and chronic
      obstructive pulmonary disease.

PMID- 29449622
TI  - Directional preparation of anticoagulant-active sulfated polysaccharides from
      Enteromorpha prolifera using artificial neural networks.
AB  - The sulfated polysaccharides from Enteromorpha prolifera (PE) are a potential
      source of anticoagulant agents. In this study, the PE was degraded by specific
      degradase and five hydrolysis products with different molecular weights were
      prepared. The product of 206 kDa is a kind of high rhamnose-containing
      polysaccharide with sulfate ester (34.29%). It could effectively prolong the
      activated partial thromboplastin time (APTT), which indicated inhibition of the
      intrinsic coagulation pathway. The artificial neural network (ANN) was built to
      realize the directional preparation of anticoagulant-active polysaccharides.
      Based on monitoring glucose concentration on-line, a visualization system of
      enzymatic hydrolysis was developed to simplify the operation of ANN. The model
      could be further applied to predict molecular weights of polysaccharides that
      possess diverse biological activities.

PMID- 29449623
TI  - Targeted disruption of the iNOS gene improves adipose tissue inflammation and
      fibrosis in leptin-deficient ob/ob mice: role of tenascin C.
AB  - BACKGROUND/OBJECTIVES: Obesity is related to a dynamic extracellular matrix (ECM)
      remodeling, which involves the synthesis and degradation of different proteins,
      such as tenascin C (TNC) in the adipose tissue (AT). Given the functional
      relationship between leptin and inducible nitric oxide synthase (iNOS), our aim
      was to analyze the impact of the absence of the iNOS gene in AT inflammation and
      ECM remodeling in ob/ob mice. SUBJECTS/METHODS: The expression of genes involved
      in inflammation and ECM remodeling was evaluated in 10-week-old male double
      knockout (DBKO) mice simultaneously lacking the ob and iNOS genes as well as in
      ob/ob mice classified into three groups [control, leptin-treated (1 mg kg-1 day
      1) and pair-fed]. RESULTS: Leptin deficiency increased inflammation and fibrosis
      in AT. As expected, leptin treatment improved the obesity phenotype. iNOS
      deficiency in ob/ob mice improved insulin sensitivity, AT inflammation, and ECM
      remodeling, as evidenced by lower AT macrophage infiltration and collagen
      deposition, a downregulation of proinflammatory and profibrogenic genes Tnf,
      Emr1, Hif1a, Col6a1, Col6a3, and Tnc, as well as lower circulating TNC levels.
      Interestingly, leptin upregulated TNC expression and release in 3T3-L1
      adipocytes, and iNOS knockdown in 3T3-L1 fat cells produced a significant
      decrease in basal and leptin-induced Tnc expression. CONCLUSIONS: Ablation of
      iNOS in leptin-deficient mice improved AT inflammation and ECM remodeling-related
      genes, attenuating fibrosis, and metabolic dysfunction. The activation of iNOS by
      leptin is necessary for the synthesis and secretion of TNC in adipocytes,
      suggesting an important role of this alarmin in the development of AT
      inflammation and fibrosis.

PMID- 29449624
TI  - A Water Droplet Pinning and Heat Transfer Characteristics on an Inclined
      Hydrophobic Surface.
AB  - A water droplet pinning on inclined hydrophobic surface is considered and the
      droplet heat transfer characteristics are examined. Solution crystallization of
      polycarbonate is carried out to create hydrophobic characteristics on the
      surface. The pinning state of the water droplet on the extreme inclined
      hydrophobic surface (0 degrees  <= delta <= 180 degrees , delta being the
      inclination angle) is assessed. Heat transfer from inclined hydrophobic surface
      to droplet is simulated for various droplet volumes and inclination angles in
      line with the experimental conditions. The findings revealed that the hydrophobic
      surface give rise to large amount of air being trapped within texture, which
      generates Magdeburg like forces between the droplet meniscus and the textured
      surface while contributing to droplet pinning at extreme inclination angles. Two
      counter rotating cells are developed for inclination angle in the range of 0
      degrees  < delta < 20 degrees  and 135 degrees  < delta < 180 degrees ; however,
      a single circulation cell is formed inside the droplet for inclination angle of
      25 degrees  <= delta <= 135 degrees . The Nusselt number remains high for the
      range of inclination angle of 45 degrees  <= delta <= 135 degrees . Convection
      and conduction heat transfer enhances when a single and large circulation cell is
      formed inside the droplet.

PMID- 29449625
TI  - Toll-like receptor 4 modulation influences human neural stem cell proliferation
      and differentiation.
AB  - Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been
      shown to regulate proliferation and differentiation of human neural stem cells
      (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from
      the human telencephalic-diencephalic area of the fetal brain and cultured in
      vitro as neurospheres in compliance with Good Manifacture Procedures (GMP)
      guidelines. Similar batches have been used in recent clinical trials in ALS
      patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD
      2 co-receptors, and TLR4 expression is downregulated upon differentiation.
      Activation of TLR4 signaling by lipopolysaccharide (LPS) has a positive effect on
      proliferation and/or survival while the inverse is observed with TLR4 inhibition
      by a synthetic antagonist. TLR4 activation promotes neuronal and oligodendrocyte
      differentiation and/or survival while TLR4 inhibition leads to increased
      apoptosis. Consistently, endogenous expression of TLR4 is retained by hNSC
      surviving after transplantation in ALS rats or immunocompromised mice, thus
      irrespectively of the neuroinflammatory environment. The characterization of
      downstream signaling of TLR4 in hNSCs has suggested some activation of the
      inflammasome pathway. This study suggests TLR4 signaling as essential for hNSC
      self-renewal and as a novel target for the study of neurogenetic mechanisms.

PMID- 29449626
TI  - Molecular dynamics study of strengthening mechanism of nanolaminated graphene/Cu
      composites under compression.
AB  - Molecular dynamics simulations of nanolaminated graphene/Cu (NGCu) and pure Cu
      under compression are conducted to investigate the underlying strengthening
      mechanism of graphene and the effect of lamella thickness. It is found that the
      stress-strain curves of NGCu undergo 3 regimes i.e. the elastic regime I, plastic
      strengthening regime II and plastic flow regime III. Incorporating graphene
      monolayer is proved to simultaneously contribute to the strength and ductility of
      the composites and the lamella thickness has a great effect on the mechanical
      properties of NGCu composites. Different strengthening mechanisms play main role
      in different regimes, the transition of mechanisms is found to be related to the
      deformation behavior. Graphene affected zone is developed and integrated with
      rule of mixtures and confined layer slip model to describe the elastic properties
      of NGCu and the strengthening effect of the incorporated graphene.

PMID- 29449627
TI  - Measurements of complex refractive index change of photoactive yellow protein
      over a wide wavelength range using hyperspectral quantitative phase imaging.
AB  - A novel optical holographic technique is presented to simultaneously measure both
      the real and imaginary components of the complex refractive index (CRI) of a
      protein solution over a wide visible wavelength range. Quantitative phase imaging
      was employed to precisely measure the optical field transmitted from a protein
      solution, from which the CRIs of the protein solution were retrieved using the
      Fourier light scattering technique. Using this method, we characterized the CRIs
      of the two dominant structural states of a photoactive yellow protein solution
      over a broad wavelength range (461-582 nm). The significant CRI deviation between
      the two structural states was quantified and analysed. The results of both states
      show the similar overall shape of the expected rRI obtained from the Kramers
      Kronig relations.

PMID- 29449628
TI  - Publisher Correction: The transcriptional coactivator TAZ regulates reciprocal
      differentiation of TH17 cells and Treg cells.
AB  - In the version of this article initially published, the institution name for
      affiliation 3 (Maryland Anderson Cancer Center) was incorrect. The correct
      institution is MD Anderson Cancer Center. The error has been corrected in the
      HTML and PDF versions of the article.

PMID- 29449629
TI  - Publisher Correction: Human gammadelta T cells are quickly reconstituted after
      stem-cell transplantation and show adaptive clonal expansion in response to viral
      infection.
AB  - In the version of this article initially published, a source of funding (Deutsche
      Jose Carreras Leukamie-Stiftung e.V. (DJCLS R12/29 to C.K. and I.P.)) was not
      included in the Acknowledgments section. The correct statement is as follows:
      "Supported by Deutsche Forschungsgemeinschaft, (SFB900/B8 to C.K. and I.P.; and
      PR727/4-1 to I.P.), Deutsche Jose Carreras Leukamie-Stiftung e.V. (DJCLS R12/29
      to C.K. and I.P.) and the German Federal Ministry of Education and Research
      (01EO1302 to C.S.-F., C.K. and I.P.)." The error has been corrected in the HTML
      and PDF versions of the article.

PMID- 29449631
TI  - Electrochemical Performance of Supercapacitor with Stacked Copper Foils Coated
      with Graphene Nanoplatelets.
AB  - The energy density of conventional supercapacitors is in the range of 6-10 Wh kg
      1, which has restricted them from many applications that require devices with
      long durations. Herein, we report a method for enhancing the energy density of a
      device through the parallel stacking of five copper foils coated on each side
      with graphene nanoplatelets. Microporous papers immersed in 2 M aqueous sodium
      sulphate were used as separators. With a low contact resistance of 0.05 Omega,
      the supercapacitor yielded an optimum specific energy density and a specific
      power density of 24.64 Wh kg-1 and 402 W kg-1 at 0.8 V, respectively. The working
      potential was increased to 2.4 V when three of the supercapacitors were connected
      in series, forming a tandem device. Its potential for real applications was
      manifested by the ability to light up a light-emitting diode for 40 s after
      charging for 60 s.

PMID- 29449632
TI  - Inducible nitric oxide synthase during the late phase of sepsis is associated
      with hypothermia and immune cell migration.
AB  - Hypothermia is a significant sign of sepsis, which is associated with poor
      prognosis, but few mechanisms underlying the regulation of hypothermia are known.
      Inducible nitric oxide synthase (iNOS) is a key inflammatory mediator of sepsis.
      However, the therapeutic benefit of iNOS inhibition in sepsis is still
      controversial, and requires elucidation in an accurate model system. In this
      study, wild-type (WT) mice showed temperature drops in a biphasic manner at the
      early and late phase of sepsis, and all mice died within 48 h of sepsis. In
      contrast, iNOS-knockout (KO) mice never showed the second temperature drop and
      exhibited improved mortality. Plasma nitric oxide (NO) levels of WT mice
      increased in the late phase of sepsis and correlated to hypothermia. The results
      indicate that iNOS-derived NO during the late phase of sepsis caused vasodilation
      induced hypothermia and a lethal hypodynamic state. The expression of the iNOS
      mRNA was high in the lung of WT mice with sepsis, which reflects the pathology of
      acute respiratory distress syndrome (ARDS). We obtained the results in a modified
      keyhole-type cecal ligation and puncture model of septic shock induced by
      minimally invasive surgery. In this accurate and reproducible model system, we
      transplanted the bone marrow cells of GFP transgenic mice into WT and iNOS-KO
      mice, and evaluated the role of increased pulmonary iNOS expression in cell
      migration during the late phase of sepsis. We also investigated the quantity and
      type of bone marrow-derived cells (BMDCs) in the lung. The number of BMDCs in the
      lung of iNOS-KO mice was less than that in the lung of WT mice. The major BMDCs
      populations were CD11b-positive, iNOS-negative cells in WT mice, and Gr-1
      positive cells in iNOS-KO mice that expressed iNOS. These results suggest that
      sustained hypothermia may be a beneficial guide for future iNOS-targeted therapy
      of sepsis, and that iNOS modulated the migratory efficiency and cell type of
      BMDCs in septic ARDS.

PMID- 29449633
TI  - A competitive cell-permeable peptide impairs Nme-1 (NDPK-A) and Prune-1
      interaction: therapeutic applications in cancer.
AB  - The understanding of protein-protein interactions is crucial in order to generate
      a second level of functional genomic analysis in human disease. Within a cellular
      microenvironment, protein-protein interactions generate new functions that can be
      defined by single or multiple modes of protein interactions. We outline here the
      clinical importance of targeting of the Nme-1 (NDPK-A)-Prune-1 protein complex in
      cancer, where an imbalance in the formation of this protein-protein complex can
      result in inhibition of tumor progression. We discuss here recent functional data
      using a small synthetic competitive cell-permeable peptide (CPP) that has shown
      therapeutic efficacy for impairing formation of the Nme-1-Prune-1 protein complex
      in mouse preclinical xenograft tumor models (e.g., breast, prostate, colon, and
      neuroblastoma). We thus believe that further discoveries in the near future
      related to the identification of new protein-protein interactions will have great
      impact on the development of new therapeutic strategies against various cancers.

PMID- 29449630
TI  - Prime and Boost Vaccination Elicit a Distinct Innate Myeloid Cell Immune
      Response.
AB  - Understanding the innate immune response to vaccination is critical in vaccine
      design. Here, we studied blood innate myeloid cells after first and second
      immunization of cynomolgus macaques with the modified vaccinia virus Ankara. The
      inflammation at the injection site was moderate and resolved faster after the
      boost. The blood concentration of inflammation markers increased after both
      injections but was lower after the boost. The numbers of neutrophils, monocytes,
      and dendritic cells were transiently affected by vaccination, but without any
      major difference between prime and boost. However, phenotyping deeper those cells
      with mass cytometry unveiled their high phenotypic diversity with subsets
      responding differently after each injection, some enriched only after the primary
      injection and others only after the boost. Actually, the composition in
      subphenotype already differed just before the boost as compared to just before
      the prime. Multivariate analysis identified the key features that contributed to
      these differences. Cell subpopulations best characterizing the post-boost
      response were more activated, with a stronger expression of markers involved in
      phagocytosis, antigen presentation, costimulation, chemotaxis, and inflammation.
      This study revisits innate immunity by demonstrating that, like adaptive
      immunity, innate myeloid responses differ after one or two immunizations.

PMID- 29449634
TI  - Self-perceptions from people with Down syndrome in Japan.
AB  - Self-perception of people with Down Syndrome (DS) was originally studied in the
      United States in 2011; this study indicated that 99% of people with DS are happy
      with their lives. In this study, we investigated self-perceptions of people with
      DS in Japan and compared the results to the previous study made in the United
      States. The participants (n = 300) were 12 years old or older and members of
      Japan Down Syndrome Society (JDS). The questionnaire was collected between 30
      October 2015 and 26 November 2015. Of 96(32%) responses, 76 (97%) agreed they are
      happy with their lives. We found that most people with DS in Japan also feel
      positive about themselves and their lives. Along with the start of Non-Invasive
      Prenatal Testing in Japan, DS draws an attention from Japanese people because
      maternal age has been increasing. This has resulted in the growth of the number
      of prenatal tests marketed in Japan. Therefore, we expect our results to be
      relevant to genetic counseling for the couples considering prenatal tests or
      parents raising their children with DS so that they have a clearer image about
      life with DS and can better visualize their life plans.

PMID- 29449635
TI  - Purkinje cells derived from TSC patients display hypoexcitability and synaptic
      deficits associated with reduced FMRP levels and reversed by rapamycin.
AB  - Accumulating evidence suggests that cerebellar dysfunction early in life is
      associated with autism spectrum disorder (ASD), but the molecular mechanisms
      underlying the cerebellar deficits at the cellular level are unclear. Tuberous
      sclerosis complex (TSC) is a neurocutaneous disorder that often presents with
      ASD. Here, we developed a cerebellar Purkinje cell (PC) model of TSC with patient
      derived human induced pluripotent stem cells (hiPSCs) to characterize the
      molecular mechanisms underlying cerebellar abnormalities in ASD and TSC. Our
      results show that hiPSC-derived PCs from patients with pathogenic TSC2 mutations
      displayed mTORC1 pathway hyperactivation, defects in neuronal differentiation and
      RNA regulation, hypoexcitability and reduced synaptic activity when compared with
      those derived from controls. Our gene expression analyses revealed downregulation
      of several components of fragile X mental retardation protein (FMRP) targets in
      TSC2-deficient hiPSC-PCs. We detected decreased expression of FMRP, glutamate
      receptor delta2 (GRID2), and pre- and post-synaptic markers such as synaptophysin
      and PSD95 in the TSC2-deficient hiPSC-PCs. The mTOR inhibitor rapamycin rescued
      the deficits in differentiation, synaptic dysfunction, and hypoexcitability of
      TSC2 mutant hiPSC-PCs in vitro. Our findings suggest that these gene expression
      changes and cellular abnormalities contribute to aberrant PC function during
      development in TSC affected individuals.

PMID- 29449636
TI  - Structural elucidation of a polysaccharide from Flammulina velutipes and its
      immunomodulation activities on mouse B lymphocytes.
AB  - A novel polysaccharide FVPB2 was purified from fruiting bodies of Flammulina
      velutipes. Its structure was elucidated by monosaccharide composition and
      methylation analyses, UV-Visible and FTIR spectroscopy as well as NMR. FVPB2 was
      a homogeneous heteropolysaccharide (molecular weight ~ 1.50 * 104 Da) containing
      D-galactose, D-mannose, L-fucose, and D-glucose at molar ratio of 1.9:1.2:1:2.5.
      In vitro immunomodulatory studies showed FVPB2 induced proliferation of mouse
      spleen lymphocytes in a dose-dependent manner. The levels of IgM and IgG,
      secreted by B cells, increased after FVPB2 treatment. So FVPB2 has potential to
      be a new important immunomodulatory nutraceutical.

PMID- 29449637
TI  - Facile emulsion mediated synthesis of phase-pure diopside nanoparticles.
AB  - Diopside is a common natural pyroxene that is rarely found in a pure state, since
      magnesium is often partially substituted by iron, and other elements (sodium and
      aluminum) are often present. This pyroxene, along with feldspars and olivines, is
      common in concrete. As the prospective license renewal of light water reactors to
      80 years of operation has raised concerns on the effects of radiation in the
      concrete biological shield surrounding the reactors, mineral nanoparticles can be
      valuable to perform amorphization studies to inform predictive models of
      mechanical properties of irradiated concrete. The synthesis of diopside
      nanoparticles was achieved in this study using a reverse-micelle sol-gel method
      employing TEOS, calcium chloride and Mg(MeO)2 in a methanol/toluene solution.
      Tert-butylamine and water were used as hydrolysis agents, and dodecylamine as a
      surfactant. The resulting amorphous precursor was centrifuged to remove organics
      and fired at 800  degrees C. Additional reaction with hydrogen peroxide was used
      to remove amine remnants. TEM and SEM examinations revealed a product comprised
      of 50-100 nm diameter nanoparticles. XRD indicated phase pure diopside and BET
      indicated a surface area of 63.5 m2/g before peroxide treatment, which at a bulk
      density of 3.4 g/cm3 is equivalent to particles with diameter of 28 nm.

PMID- 29449638
TI  - Protection from experimental cerebral malaria with a single intravenous or
      subcutaneous whole-parasite immunization.
AB  - Cerebral malaria is a life-threatening complication of Plasmodia infection and a
      major cause of child mortality in Sub-Saharan Africa. We report that protection
      from experimental cerebral malaria in the rodent model is obtained by a single
      intravenous or subcutaneous whole-parasite immunization. Whole-parasite
      immunization with radiation-attenuated sporozoites was equally protective as
      immunization with non-attenuated sporozoites under chemoprophylaxis. Both
      immunization regimens delayed the development of blood-stage parasites, but
      differences in cellular and humoral immune mechanisms were observed. Single-dose
      whole-parasite vaccination might serve as a relatively simple and feasible
      immunization approach to prevent life-threatening cerebral malaria.

PMID- 29449639
TI  - A hERG mutation E1039X produced a synergistic lesion on IKs together with KCNQ1
      R174C mutation in a LQTS family with three compound mutations.
AB  - Congenital long QT syndrome (LQTS) caused by compound mutations is usually
      associated with more severe clinical phenotypes. We identified a LQTS family
      harboring three compound mutations in different genes (KCNQ1-R174C, hERG-E1039X
      and SCN5A-E428K). KCNQ1-R174C, hERG-E1039X and SCN5A-E428K mutations and/or
      relevant wild-type (WT) cDNAs were respectively expressed in mammalian cells. IKs
      like, IKr-like, INa-like currents and the functional interaction between KCNQ1
      R174C and hERG-E1039X channels were studied using patch-clamp and
      immunocytochemistry techniques. (1) Expression of KCNQ1-R174C alone showed no
      IKs. Co-expression of KCNQ1-WT + KCNQ1-R174C caused a loss-of-function in IKs and
      blunted the activation of IKs in response to isoproterenol. (2) Expression of
      hERG-E1039X alone and co-expression of hERG-WT + hERG-E1039X negatively shifted
      inactivation curves and decelerated the recovery time from inactivation. (3)
      Expression of SCN5A-E428K increased peak INa, but had no effect on late INa. (4)
      IKs and IKr interact, and hERG-E1039X caused a loss-of-function in IKs. (5)
      Immunocytochemical studies indicated that KCNQ1-R174C is trafficking defective
      and hERG-E1039X is defective in biosynthesis/degradation, but the abnormities
      were rescued by co-expression with WT. Thus, KCNQ1-R174C and hERG-E1039X
      disrupted IKs and IKr functions, respectively. The synergistic lesion, caused by
      KCNQ1-R174C and hERG-E1039X in IKs, is very likely why patients showed more
      severe phenotypes in the compound mutation case.

PMID- 29449640
TI  - Corrigendum: Treponema pallidum (syphilis) antigen TpF1 induces angiogenesis
      through the activation of the IL-8 pathway.
AB  - This corrects the article DOI: 10.1038/srep18785.

PMID- 29449641
TI  - A Multifunctional Nanocage-based MOF with Tri- and Tetranuclear Zinc Cluster
      Secondary Building Units.
AB  - A new Zn-cluster based MOF, [Zn21(BTC)11(MU3-OH)3(MU4-O)3(H2O)18].21EtOH (1)
      (H3BTC = 1,3,5-benzenetricarboxylic acid), with two different types of cluster
      nodes has been successfully synthesized from Zn2+ and H3BTC under the
      solvothermal conditions. Single crystal X-ray diffraction studies reveal that 1
      is a 3D trinodal (3,5,6)-c framework which features a large octahedral cage
      organized by nine Zn3O and nine Zn4O clusters SBUs and twenty-four triangular
      BTC3- linkers. The Eu3+/Tb3+-incorporated derivative of 1 with 0.251% Eu3+ and
      0.269% Tb3+ exhibits tunable luminescence from yellow to white and then to blue
      green by changing the excitation wavelength from 308 to 315 nm. Metal ion
      exchange with Cu2+ affords isomorphous Cu-based MOF with enhanced N2 and CO2
      adsorption capacity. In addition, 1 can act as a selective luminescent sensor for
      Cu2+ and Al3+ ions.

PMID- 29449642
TI  - NIT1 suppresses tumour proliferation by activating the TGFbeta1-Smad2/3
      signalling pathway in colorectal cancer.
AB  - NIT1 protein has been reported to be a potential tumour suppressor in tumour
      progression. However, little is known about the specific role of NIT1 in tumour
      development and progression. In this study, we confirmed the specific effects of
      NIT1 in the regulation of colorectal carcinoma cell proliferation. Here, we
      showed that NIT1 was significantly downregulated in colorectal cancer tissues
      compared with that in adjacent normal tissues. The decreased expression of NIT1
      was significantly correlated with poor differentiation and more serosal invasion.
      Functional experiments showed that NIT1 inhibited CRC cell growth both in vitro
      and in vivo. NIT1 induced cell cycle arrest and apoptosis. Furthermore, NIT1
      recruited Smad2/3 to the TGFbeta receptor and activated the TGFbeta-Smad2/3
      pathway by interacting with SARA and SMAD2/3 in CRC. Further study has shown that
      SMAD3 directly binds to the promoter regions of NIT1 and enhances the
      transcription of NIT1. Together, our findings indicate that NIT1 suppresses CRC
      proliferation through a positive feedback loop between NIT1 and activation of the
      TGFbeta-Smad signalling pathway. This study might provide a new promising
      strategy for CRC.

PMID- 29449643
TI  - SIRT2 regulates oxidative stress-induced cell death through deacetylation of c
      Jun NH2-terminal kinase.
AB  - c-Jun NH2-terminal kinases (JNKs) are responsive to stress stimuli and their
      activation regulate key cellular functions, including cell survival, growth,
      differentiation and aging. Previous studies demonstrate that activation of JNK
      requires dual phosphorylation by the mitogen-activated protein kinase kinases.
      However, other post-translational mechanisms involved in regulating the activity
      of JNK have been poorly understood. In this work, we studied the functional
      significance of reversible lysine acetylation in regulating the kinase activity
      of JNK. We found that the acetyl transferase p300 binds to, acetylates and
      inhibits kinase activity of JNK. Using tandem mass spectrometry, molecular
      modelling and molecular dynamics simulations, we found that acetylation of JNK at
      Lys153 would hinder the stable interactions of the negatively charged phosphates
      and prevent the adenosine binding to JNK. Our screening for the deacetylases
      found SIRT2 as a deacetylase for JNK. Mechanistically, SIRT2-dependent
      deacetylation enhances ATP binding and enzymatic activity of JNK towards c-Jun.
      Furthermore, SIRT2-mediated deacetylation favours the phosphorylation of JNK by
      MKK4, an upstream kinase. Our results indicate that deacetylation of JNK by SIRT2
      promotes oxidative stress-induced cell death. Conversely, SIRT2 inhibition
      attenuates H2O2-mediated cell death in HeLa cells. SIRT2-deficient (SIRT2-KO)
      mice exhibit increased acetylation of JNK, which is associated with markedly
      reduced catalytic activity of JNK in the liver. Interestingly, SIRT2-KO mice were
      resistant to acetaminophen-induced liver toxicity. SIRT2-KO mice show lower cell
      death, minimal degenerative changes, improved liver function and survival
      following acetaminophen treatment. Overall, our work identifies SIRT2-mediated
      deacetylation of JNK as a critical regulator of cell survival during oxidative
      stress.

PMID- 29449645
TI  - EGFR-PI3K-PDK1 pathway regulates YAP signaling in hepatocellular carcinoma: the
      mechanism and its implications in targeted therapy.
AB  - The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an
      important role in the carcinogenesis of hepatocellular carcinoma (HCC). However,
      the crosstalk between these two pathways and its implications in targeted therapy
      remains unclear. We found that the activated EGFR signaling could bypass RhoA to
      promote the expression of YAP(Yes-associated protein), the core effector of the
      Hippo signaling, and its downstream target Cyr61. Further studies indicated that
      EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase
      Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and
      MAPK pathways. While YAP knockdown hardly affected the EGFR signaling. In
      addition, EGF could promote the proliferation of HCC cells in a YAP-independent
      manner. Combined targeting of YAP and EGFR signaling by simvastatin and the EGFR
      signaling inhibitors, including the EGFR tyrosine kinase inhibitor (TKI)
      gefitinib, the RAF inhibitor sorafenib and the MEK inhibitor trametinib,
      presented strong synergistic cytotoxicities in HCC cells. Therefore, the EGFR
      PI3K-PDK1 pathway could activate the YAP signaling, and the activated EGFR
      signaling could promote the HCC cell growth in a YAP-independent manner. Combined
      use of FDA-approved inhibitors to simultaneously target YAP and EGFR signaling
      presented several promising therapeutic approaches for HCC treatment.

PMID- 29449644
TI  - Inhibition of the JNK/MAPK signaling pathway by myogenesis-associated miRNAs is
      required for skeletal muscle development.
AB  - Skeletal muscle differentiation is controlled by multiple cell signaling
      pathways, however, the JNK/MAPK signaling pathway dominating this process has not
      been fully elucidated. Here, we report that the JNK/MAPK pathway was
      significantly downregulated in the late stages of myogenesis, and in contrast to
      P38/MAPK pathway, it negatively regulated skeletal muscle differentiation. Based
      on the PAR-CLIP-seq analysis, we identified six elevated miRNAs (miR-1a-3p, miR
      133a-3p, miR-133b-3p, miR-206-3p, miR-128-3p, miR-351-5p), namely myogenesis
      associated miRNAs (mamiRs), negatively controlled the JNK/MAPK pathway by
      repressing multiple factors for the phosphorylation of the JNK/MAPK pathway,
      including MEKK1, MEKK2, MKK7, and c-Jun but not JNK protein itself, and as a
      result, expression of transcriptional factor MyoD and mamiRs were further
      promoted. Our study revealed a novel double-negative feedback regulatory pattern
      of cell-specific miRNAs by targeting phosphorylation kinase signaling cascade
      responsible for skeletal muscle development.

PMID- 29449646
TI  - Assessing cetacean surveys throughout the Mediterranean Sea: a gap analysis in
      environmental space.
AB  - Heterogeneous data collection in the marine environment has led to large gaps in
      our knowledge of marine species distributions. To fill these gaps, models
      calibrated on existing data may be used to predict species distributions in
      unsampled areas, given that available data are sufficiently representative. Our
      objective was to evaluate the feasibility of mapping cetacean densities across
      the entire Mediterranean Sea using models calibrated on available survey data and
      various environmental covariates. We aggregated 302,481 km of line transect
      survey effort conducted in the Mediterranean Sea within the past 20 years by many
      organisations. Survey coverage was highly heterogeneous geographically and
      seasonally: large data gaps were present in the eastern and southern
      Mediterranean and in non-summer months. We mapped the extent of interpolation
      versus extrapolation and the proportion of data nearby in environmental space
      when models calibrated on existing survey data were used for prediction across
      the entire Mediterranean Sea. Using model predictions to map cetacean densities
      in the eastern and southern Mediterranean, characterised by warmer, less
      productive waters, and more intense eddy activity, would lead to potentially
      unreliable extrapolations. We stress the need for systematic surveys of cetaceans
      in these environmentally unique Mediterranean waters, particularly in non-summer
      months.

PMID- 29449647
TI  - The pro-inflammatory phenotype of the human non-classical monocyte subset is
      attributed to senescence.
AB  - Human primary monocytes comprise a heterogeneous population that can be
      classified into three subsets based on CD14 and CD16 expression: classical
      (CD14high/CD16-), intermediate (CD14high/CD16+), and non-classical
      (CD14low/CD16+). The non-classical monocytes are the most pro-inflammatory in
      response to TLR stimulation in vitro, yet they express a remarkably high basal
      level of miR-146a, a microRNA known to negatively regulate the TLR pathway. This
      concurrence of a pro-inflammatory status and a high miR-146a level has been
      associated with cellular senescence in other cell types. Hence, we assessed the
      three monocyte subsets for evidence of senescence, including proliferative
      status, telomere length, cellular ROS levels, and mitochondrial membrane
      potential. Indeed, the non-classical subset exhibited the clearest hallmarks of
      senescence, followed by the intermediate and then the classical subset. In
      addition, the non-classical subset secreted pro-inflammatory cytokines basally in
      vitro. The highly pro-inflammatory nature of the non-classical monocytes could be
      a manifestation of the senescence-associated secretory phenotype (SASP), likely
      induced by a high basal NF-kappaB activity and IL-1alpha production. Finally, we
      observed an accumulation of the non-classical monocytes, in conjunction with
      higher levels of plasma TNF-alpha and IL-8, in the elderly. These factors may
      contribute to inflamm-aging and age-related inflammatory conditions, such as
      atherosclerosis and osteoarthritis. With our new understanding that the non
      classical monocyte subset is a senescent population, we can now re-examine the
      role of this subset in disease conditions where this subset expands.

PMID- 29449648
TI  - The role of disease-linked residue glutamine-913 in support of the structure and
      function of the human electrogenic sodium/bicarbonate cotransporter NBCe1-A.
AB  - Mutations in the sodium bicarbonate cotransporter NBCe1 (SLC4A4) cause proximal
      renal tubular acidosis (pRTA). We recently described a novel pRTA mutation
      p.Gln913Arg (Q913R), inherited in compound heterozygous form with p.Arg510His
      (R510H). Q913R causes intracellular retention of NBCe1 and a 'gain of function'
      Cl- leak. To learn more about the importance of glutamine at position 913, we
      substituted a variety of alternative amino-acid residues (Cys, Glu, Lys, Leu,
      Ser) at position 913. Studying cRNA-injected Xenopus oocytes by voltage clamp, we
      find that most de novo mutants exhibit close-to-normal NBCe1 activity; only Q913K
      expresses a Cl- leak. Studying transiently-transfected, polarised kidney cells by
      fluorescence microscopy we find that most de novo mutants (except Q913E) are
      intracellularly retained. A 3D homology model predicts that Gln913 is located in
      the gating domain of NBCe1 and neighbours the 3D space occupied by another pRTA
      associated residue (Arg881), highlighting an important and conformationally
      sensitive region of NBCe1. We conclude that the intracellular retention of Q913R
      is caused by the loss of Gln at position 913, but that the manifestation of the
      Cl- leak is related to the introduction of Arg at position 913. Our findings will
      inform future studies to elucidate the nature and the consequences of the leak.

PMID- 29449649
TI  - Predicting sex from brain rhythms with deep learning.
AB  - We have excellent skills to extract sex from visual assessment of human faces,
      but assessing sex from human brain rhythms seems impossible. Using deep
      convolutional neural networks, with unique potential to find subtle differences
      in apparent similar patterns, we explore if brain rhythms from either sex contain
      sex specific information. Here we show, in a ground truth scenario, that a deep
      neural net can predict sex from scalp electroencephalograms with an accuracy of
      >80% (p < 10-5), revealing that brain rhythms are sex specific. Further, we
      extracted sex-specific features from the deep net filter layers, showing that
      fast beta activity (20-25 Hz) and its spatial distribution is a main distinctive
      attribute. This demonstrates the ability of deep nets to detect features in
      spatiotemporal data unnoticed by visual assessment, and to assist in knowledge
      discovery. We anticipate that this approach may also be successfully applied to
      other specialties where spatiotemporal data is abundant, including neurology,
      cardiology and neuropsychology.

PMID- 29449650
TI  - The transition from dental school to postgraduate dental foundation training:
      strengthening the interaction between stakeholders.
AB  - This article demonstrates the benefits of collaboration between dental educators
      in undergraduate and postgraduate settings, to facilitate the transition of
      dental students into dental foundation training (DFT). The School of Dental
      Sciences at Newcastle University and Health Education England, working across
      north-east and north Cumbria, have strengthened links by forming a dental
      foundation programme undergraduate liaison group (FPUG) involving all
      stakeholders. The group has shared information between the organisations,
      enhanced stakeholder engagement, and developed several initiatives including
      workshops to help prepare final year students for the transition to DFT. A small
      investment in time has been highly effective, and the formation of a similar
      group merits consideration in other areas of the UK.

PMID- 29449652
TI  - Serious concerns about the General Dental Council's performance and its direction
      of travel.
AB  - There should be tension between a profession and its regulator, it would be odd
      if it were not so, but the level of concern that has been articulated recently by
      some high profile commentators about that relationship has been well beyond what
      I would describe as tension. In this piece I attempt to contextualise my personal
      observations and comments on what is rapidly becoming a serious concern among
      those few of us who have had to deal with the profession: regulator interface at
      the highest level.

PMID- 29449651
TI  - Beyond Streptococcus mutans: clinical implications of the evolving dental caries
      aetiological paradigms and its associated microbiome.
AB  - Aetiological concepts of dental caries have evolved over the years from being
      considered as a disease initiated by nonspecific microorganisms, to being
      regarded as an 'infectious' disease caused by specific bacteria, to the current
      paradigms that emphasise a 'mixed bacterial-ecological approach' as being
      responsible for lesion initiation and pathogenesis. These aetiological paradigms
      are not just intellectual concepts but have important implications on how
      clinicians manage this age-old disease in the twenty-first century. Despite
      evidence-backed recommendations for adopting more biological measures to counter
      the disease, a significant proportion of dentists continue following traditional
      caries management guidelines in their daily clinical practice. This paper will
      review the evolving dental caries aetiological concepts and highlight the current
      evidence for adopting a more ecological approach to caries prevention, risk
      assessment, and treatment.

PMID- 29449653
TI  - CFTR mutation enhances Dishevelled degradation and results in impairment of Wnt
      dependent hematopoiesis.
AB  - Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause
      cystic fibrosis (CF) with a multitude of clinical manifestations. Some CF
      patients develop clinically significant anemia, suggesting that CFTR may regulate
      hematopoiesis. Here, we report that cftr mutant zebrafish model exhibits
      primitive and definitive hematopoietic defects with impaired Wnt signaling. Cftr
      is found to interact, via its PDZ-binding domain (PDZBD), with Dishevelled (Dvl),
      a key component of Wnt signaling required for hematopoietic progenitor
      specification, thus protecting Dvl from Dapper1 (Dpr1)-induced lysosomal
      degradation. Defective hematopoiesis and impaired Wnt signaling in cftr mutant
      can be rescued by overexpression of wild-type or channel function-defective G551D
      mutant CFTR with an intact PDZBD, but not Cftr with mutations in the PDZBD.
      Analysis of human database ( http://r2.amc.nl ) shows that CFTR is positively
      correlated with DVL2 and Wnt-related hematopoietic factors in human blood system.
      The results reveal a previously unrecognized role of CFTR, which is independent
      of its channel function, in regulating DVL degradation and thus Wnt signaling
      required for hematopoiesis in both zebrafish and humans, providing an explanation
      for the anemic phenotype of CF patients.

PMID- 29449655
TI  - Observationally quantified reconnection providing a viable mechanism for active
      region coronal heating.
AB  - The heating of the Sun's corona has been explained by several different
      mechanisms including wave dissipation and magnetic reconnection. While both have
      been shown capable of supplying the requisite power, neither has been used in a
      quantitative model of observations fed by measured inputs. Here we show that
      impulsive reconnection is capable of producing an active region corona agreeing
      both qualitatively and quantitatively with extreme-ultraviolet observations. We
      calculate the heating power proportional to the velocity difference between
      magnetic footpoints and the photospheric plasma, called the non-ideal velocity.
      The length scale of flux elements reconnected in the corona is found to be around
      160 km. The differential emission measure of the model corona agrees with that
      derived using multi-wavelength images. Synthesized extreme-ultraviolet images
      resemble observations both in their loop-dominated appearance and their intensity
      histograms. This work provides compelling evidence that impulsive reconnection
      events are a viable mechanism for heating the corona.

PMID- 29449656
TI  - Ultrasound beam steering of oxygen nanobubbles for enhanced bladder cancer
      therapy.
AB  - New intravesical treatment approaches for bladder cancer are needed as currently
      approved treatments show several side effects and high tumor recurrence rate. Our
      study used MB49 murine urothelial carcinoma model to evaluate oxygen encapsulated
      cellulosic nanobubbles as a novel agent for imaging and ultrasound guided drug
      delivery. In this study, we show that oxygen nanobubbles (ONB) can be propelled
      (up to 40 mm/s) and precisely guided in vivo to the tumor by an ultrasound beam.
      Nanobubble velocity can be controlled by altering the power of the ultrasound
      Doppler beam, while nanobubble direction can be adjusted to different desired
      angles by altering the angle of the beam. Precise ultrasound beam steering of
      oxygen nanobubbles was shown to enhance the efficacy of mitomycin-C, resulting in
      significantly lower tumor progression rates while using a 50% lower concentration
      of chemotherapeutic drug. Further, dark field imaging was utilized to visualize
      and quantify the ONB ex vivo. ONBs were found to localize up to 500 um inside the
      tumor using beam steering. These results demonstrate the potential of an oxygen
      nanobubble drug encapsulated system to become a promising strategy for targeted
      drug delivery because of its multimodal (imaging and oxygen delivery) and
      multifunctional (targeting and hypoxia programming) properties.

PMID- 29449654
TI  - Analysis combining correlated glaucoma traits identifies five new risk loci for
      open-angle glaucoma.
AB  - Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify
      new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG
      cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data
      for intraocular pressure (IOP) and optic disc parameters (the overall meta
      analysis sample size varying between 32,000 to 48,000 participants), which are
      glaucoma-related traits. We identified and independently validated four novel
      genome-wide significant associations within or near MYOF and CYP26A1, LINC02052
      and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9)
      using gene-based tests, and two genetic pathways - "response to fluid shear
      stress" and "abnormal retina morphology" - in pathway-based tests. Interestingly,
      some of the new risk loci contribute to risk of other genetically-correlated eye
      diseases including myopia and age-related macular degeneration. To our knowledge,
      this study is the first integrative study to combine genetic data from OAG and
      its correlated traits to identify new risk variants and genetic pathways,
      highlighting the future potential of combining genetic data from genetically
      correlated eye traits for the purpose of gene discovery and mapping.

PMID- 29449657
TI  - Neural activity induced by visual food stimuli presented out of awareness: a
      preliminary magnetoencephalography study.
AB  - Obesity is a major public health problem in modern society. Appetitive behavior
      has been proposed to be partially driven by unconscious decision-making processes
      and thus, targeting the unconscious cognitive processes related to eating
      behavior is essential to develop strategies for overweight individuals and obese
      patients. Here, we presented food pictures below the threshold of awareness to
      healthy male volunteers and examined neural activity related to appetitive
      behavior using magnetoencephalography. We found that, among participants who did
      not recognize food pictures during the experiment, an index of heart rate
      variability assessed by electrocardiography (low-frequency component power/high
      frequency component power ratio, LF/HF) just after picture presentation was
      increased compared with that just before presentation, and the increase in LF/HF
      was negatively associated with the score for cognitive restraint of food intake.
      In addition, increased LF/HF was negatively associated with increased alpha band
      power in Brodmann area (BA) 47 caused by food pictures presented below the
      threshold of awareness, and level of cognitive restraint was positively
      associated with increased alpha band power in BA13. Our findings may provide
      valuable clues to the development of methods assessing unconscious regulation of
      appetite and offer avenues for further study of the neural mechanisms related to
      eating behavior.

PMID- 29449658
TI  - Subduction of a low-salinity water mass around the Xisha Islands in the South
      China Sea.
AB  - Based on three climatologically observed temperature and salinity datasets (i.e.,
      GDEM-V3, SCSPOD14 and WOA13), this paper reports a low-salinity (~34.32) water
      mass in the subsurface-to-intermediate layer around the Xisha Islands in the
      South China Sea. This water mass mainly subducts from the surface layer into the
      intermediate layer, characterized by a relatively low potential vorticity tongue
      extending from the bottom of mixed layer to the thermocline, and accompanied by a
      thermocline ventilation in spring (especially in April). The potential dynamics
      are the joint effects of negative wind stress curl, and an anticyclonic eddy
      triggered by the inherent topographic effect of the Xisha Islands, reflecting
      that downward vertical motion dominates the subduction. Despite lacking of the
      homogenous temperature and density, the low-salinity water mass is to some extent
      similar to the classic mode water and can be regarded as a deformed mode water in
      the South China Sea.

PMID- 29449659
TI  - Using immunotherapy to boost the abscopal effect.
AB  - More than 60 years ago, the effect whereby radiotherapy at one site may lead to
      regression of metastatic cancer at distant sites that are not irradiated was
      described and called the abscopal effect (from 'ab scopus', that is, away from
      the target). The abscopal effect has been connected to mechanisms involving the
      immune system. However, the effect is rare because at the time of treatment,
      established immune-tolerance mechanisms may hamper the development of
      sufficiently robust abscopal responses. Today, the growing consensus is that
      combining radiotherapy with immunotherapy provides an opportunity to boost
      abscopal response rates, extending the use of radiotherapy to treatment of both
      local and metastatic disease. In this Opinion article, we review evidence for
      this growing consensus and highlight emerging limitations to boosting the
      abscopal effect using immunotherapy. This is followed by a perspective on current
      and potential cross-disciplinary approaches, including the use of smart materials
      to address these limitations.

PMID- 29449661
TI  - Ocean science research is key for a sustainable future.
AB  - Human activity has already affected all parts of the ocean, with pollution
      increasing and fish-stocks plummeting. The UN's recent announcement of a Decade
      of Ocean Science provides a glimmer of hope, but scientists will need to work
      closely with decision-makers and society at large to get the ocean back on track.

PMID- 29449660
TI  - Gut microbiota injury in allogeneic haematopoietic stem cell transplantation.
AB  - Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered to
      be the strongest curative immunotherapy for various malignancies (primarily, but
      not limited to, haematologic malignancies). However, application of allo-HSCT is
      limited owing to its life-threatening major complications, such as graft-versus
      host disease (GVHD), relapse and infections. Recent advances in large-scale DNA
      sequencing technology have facilitated rapid identification of the microorganisms
      that make up the microbiota and evaluation of their interactions with host
      immunity in various diseases, including cancer. This has resulted in renewed
      interest regarding the role of the intestinal flora in patients with
      haematopoietic malignancies who have received an allo-HSCT and in whether the
      microbiota affects clinical outcomes, including GVHD, relapse, infections and
      transplant-related mortality. In this Review, we discuss the potential role of
      intestinal microbiota in these major complications after allo-HSCT, summarize
      clinical trials evaluating the microbiota in patients who have received allo-HSCT
      and discuss how further studies of the microbiota could inform the development of
      strategies that improve outcomes of allo-HSCT.

PMID- 29449662
TI  - Assessment of interaction between maternal polycyclic aromatic hydrocarbons
      exposure and genetic polymorphisms on the risk of congenital heart diseases.
AB  - The major causes of congenital heart diseases (CHDs) are the interactions of
      genetic and environmental factors. We conducted a case-control study in 357
      mothers of CHDs fetuses and 270 control mothers to investigate the association of
      maternal PAHs exposure, AHR, CYP1A1, CYP1A2, CYP1B1 and CYP2E polymorphisms, the
      interaction between PAHs exposure and genetic variants with the risk of CHDs. The
      higher level PAHs exposure was associated with the risk of CHDs (aOR = 2.029, 95%
      CI: 1.266, 3.251) or subtypes. The haplotypes of AHR or CYP1A2 were associated
      with the risk of CHDs: AHR: C-G-A-C: aOR = 0.765; T-A-G-A: aOR = 1.33; CYP1A2: A
      T:aOR = 1.75; C-C: aOR = 0.706. When exposed to higher level PAHs, the risk of
      CHDs among the mothers carrying rs2158041 "C/T or T/T" genotype or rs7811989 "G/A
      or A/A" genotype in AHR was 1.724 (chi2 = 7.209, P = 0.007) or 1.735 (chi2 =
      7.364, P = 0.007) times greater than the aOR in the mothers carrying wild
      genotype. The multiplicative-scale interactions between PAHs exposure and
      polymorphisms of CYP1A2 rs4646425 (P = 0.03) or CYP2E1 rs915908 (P = 0.0238) on
      the risk of CHDs were observed. Our study suggests that maternal AHR
      polymorphisms may modify the association of PAHs exposure with CHDs, CYP1A2 or
      CYP2E1 polymorphisms significantly interact with PAHs exposure on CHDs.

PMID- 29449663
TI  - Quantitative Evaluation of Pain during Electrocutaneous Stimulation using a Log
      Linearized Peripheral Arterial Viscoelastic Model.
AB  - In clinical practice, subjective pain evaluations, e.g., the visual analogue
      scale and the numeric rating scale, are generally employed, but these are limited
      in terms of their ability to detect inaccurate reports, and are unsuitable for
      use in anesthetized patients or those with dementia. We focused on the peripheral
      sympathetic nerve activity that responds to pain, and propose a method for
      evaluating pain sensation, including intensity, sharpness, and dullness, using
      the arterial stiffness index. In the experiment, electrocardiogram, blood
      pressure, and photoplethysmograms were obtained, and an arterial viscoelastic
      model was applied to estimate arterial stiffness. The relationships among the
      stiffness index, self-reported pain sensation, and electrocutaneous stimuli were
      examined and modelled. The relationship between the stiffness index and pain
      sensation could be modelled using a sigmoid function with high determination
      coefficients, where R2 >= 0.88, p < 0.01 for intensity, R2 >= 0.89, p < 0.01 for
      sharpness, and R2 >= 0.84, p < 0.01 for dullness when the stimuli could
      appropriately evoke dull pain.

PMID- 29449664
TI  - Incidence and clinical characteristics of ciguatera fish poisoning in Guadeloupe
      (French West Indies) between 2013 and 2016: a retrospective cases-series.
AB  - This retrospective case study analysed the incidence and symptoms of ciguatera
      fish poisoning (ciguatera) in Guadeloupe (French West Indies) between 2013 and
      2016. Cases attending the emergency departments of the two public hospitals and
      the reports received by the regional health authority in charge of monitoring
      (ARS) were compiled. Two hundred and thirty-four cases of poisoning were
      observed, with a mean annual incidence of 1.47/10,000 (95% CI): 1.29-1.66), i.e 5
      times higher than the previously reported incidence (1996-2006). The main species
      described as being responsible for poisoning were fish from the Carangidae family
      (n = 47) (jack), followed by fish from the Lutjanidae family (n = 27) (snapper),
      Serranidae family (n = 15) (grouper), Sphyraenidae family (n = 12) (barracuda),
      and Mullidae family (n = 12) (goatfish). One case of lionfish ciguatera was
      observed. 93.9% of patients experienced gastrointestinal symptoms, 76.0%
      presented neurological signs (mainly paresthesia, dysesthesia and pruritus) and
      40.3% presented cardiovascular symptoms (bradycardia and/or hypotension). A high
      frequency (61.4%) of hypothermia (body temperature <36.5  degrees C) was
      observed. This study reports for the first time the relatively high frequency of
      cardiac symptoms and low body temperature. The monitoring of ciguatera poisoning
      throughout the Caribbean region must be improved, notably after reef disturbance
      due to Irma and Maria major cyclones.

PMID- 29449665
TI  - Prediction of vaginal birth after cesarean delivery in Chinese parturients.
AB  - There is an urgent need in China to better predict vaginal birth after cesarean
      (VBAC) to face the challenge of the second child policy. We aimed to validate a
      widely used VBAC prediction model (Grobman's model) and a modified version of
      this model in a Chinese population. In this retrospective cohort study, 444 women
      with one cesarean delivery and at least one subsequent attempt for a trial of
      labor in Nanjing, China were included. The considered potential VBAC predictors
      included Grobman's background variables and five new variables. Overall, a total
      of 370 women had VBAC, with a success rate of 83.3%. The new background variables
      "maternal height" and "estimated fetal weight" were considered as two additional
      predictors for VBAC. The AUC of Grobman's model was 0.831 (95%CI = 0.775-0.886)
      while the AUC of our modified model with two new variables added was 0.857
      (sensitivity = 72.2%, specificity = 83.8%). However, the difference between the
      AUC of the two models was not significant (Z = -1.69, P = 0.091). We confirmed
      that Grobman's model was accepted in the Chinese population. A modified model
      that is supplemented with maternal height and estimated fetal weight needs to be
      further studied in the Chinese population.

PMID- 29449666
TI  - Thinning Effects on Biomass and Carbon Stock for Young Taiwania Plantations.
AB  - Forests play an important role as carbon sinks by sequestrating carbon through
      photosynthesis. Thinning treatments have large impacts on carbon storage, in
      addition to strengthening quality and quantity of plantations. This study
      analyzed the effects of different thinning treatments on carbon stocks in both
      individual trees and stands of Taiwania (Taiwania cryptomerioides) plantations.
      Repeated field measurements and allometric equations were used to calculate total
      C storage and sequestration rates of live trees. The results of this study showed
      that the total carbon stock of stands with thinning treatments was less than that
      of the non-thinned stands. The non-thinned 23-year old stands had an estimated
      carbon stock of 96.8 Mg C ha-1, which is higher than the carbon stock found in
      either medium- (84.1 Mg C ha-1) or heavily-thinned (74.7 Mg C ha-1) treatment
      plots of the same age. If the objective of Taiwania plantations was to store
      large amounts of carbon in the young growth stage, without regard to the initial
      rate of storage, a better option is no-thinning. However, the medium thinned
      forests seem to be more promising for carbon sequestration than the no-thinned
      forests if a longer period is considered.

PMID- 29449667
TI  - Identification of G-quadruplex clusters by high-throughput sequencing of whole
      genome amplified products with a G-quadruplex ligand.
AB  - G-quadruplex (G4) is a DNA secondary structure that has been found to play
      regulatory roles in the genome. The identification of G4-forming sequences is
      important to study the specific structure-function relationships of such regions.
      In the present study, we developed a method for identification of G4 clusters on
      genomic DNA by high-throughput sequencing of genomic DNA amplified via whole
      genome amplification (WGA) in the presence of a G4 ligand. The G4 ligand
      specifically bound to G4 structures on genomic DNA; thus, DNA polymerase was
      arrested on the G4 structures stabilised by G4 ligand. We utilised the
      telomestatin derivative L1H1-7OTD as a G4 ligand and demonstrated that the
      efficiency of amplification of the G4 cluster regions was lower than that of the
      non-G4-forming regions. By high-throughput sequencing of the WGA products, 9,651
      G4 clusters were identified on human genomic DNA. Among these clusters, 3,766 G4
      clusters contained at least one transcriptional start site, suggesting that genes
      are regulated by G4 clusters rather than by one G4 structure.

PMID- 29449668
TI  - Rhinovirus 3C protease suppresses apoptosis and triggers caspase-independent cell
      death.
AB  - Apoptosis and programmed necrosis (necroptosis) determine cell fate, and
      antagonize infection. Execution of these complementary death pathways involves
      the formation of receptor-interacting protein kinase 1 (RIPK1) containing
      complexes. RIPK1 binds to adaptor proteins, such as TRIF (Toll-IL-1 receptor
      domain-containing-adaptor-inducing interferon-beta factor), FADD (Fas-associated
      protein with death domain), NEMO (NF-kappaB regulatory subunit IKKgamma), SQSTM1
      (sequestosome 1/p62), or RIPK3 (receptor-interacting protein kinase 3), which are
      involved in RNA sensing, NF-kappaB signaling, autophagosome formation, apoptosis,
      and necroptosis. We report that a range of rhinoviruses impair apoptosis and
      necroptosis in epithelial cells late in infection. Unlike the double-strand (ds)
      RNA mimetic poly I:C (polyinosinic:polycytidylic acid), the exposure of dsRNA to
      toll-like receptor 3 (TLR3) in rhinovirus-infected cells did not lead to
      apoptosis execution. Accordingly, necroptosis and the production of ROS (reactive
      oxygen species) were not observed late in infection, when RIPK3 was absent.
      Instead, a virus-induced alternative necrotic cell death pathway proceeded, which
      led to membrane rupture, indicated by propidium iodide staining. The impairment
      of dsRNA-induced apoptosis late in infection was controlled by the viral 3C
      protease (3Cpro), which disrupted RIPK1-TRIF/FADD /SQSTM1 immune-complexes. 3Cpro
      and 3C precursors were found to coimmuno-precipitate with RIPK1, cleaving the
      RIPK1 death-domain, and generating N-terminal RIPK1 fragments. The depletion of
      RIPK1 or chemical inhibition of its kinase at the N-terminus did not interfere
      with virus progeny formation or cell fate. The data show that rhinoviruses
      suppress apoptosis and necroptosis, and release progeny by an alternative cell
      death pathway, which is controlled by viral proteases modifying innate immune
      complexes.

PMID- 29449669
TI  - Predictive Biomarkers of Gastroesophageal Reflux Disease and Barrett's Esophagus
      in World Trade Center Exposed Firefighters: a 15 Year Longitudinal Study.
AB  - Gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE), which are
      prevalent in the World Trade Center (WTC) exposed and general populations,
      negatively impact quality of life and cost of healthcare. GERD, a risk factor of
      BE, is linked to obstructive airways disease (OAD). We aim to identify serum
      biomarkers of GERD/BE, and assess the respiratory and clinical phenotype of a
      longitudinal cohort of never-smoking, male, WTC-exposed rescue workers presenting
      with pulmonary symptoms. Biomarkers collected soon after WTC-exposure were
      evaluated in optimized predictive models of GERD/BE. In the WTC-exposed cohort,
      the prevalence of BE is at least 6 times higher than in the general population.
      GERD/BE cases had similar lung function, D LCO , bronchodilator response and long
      acting beta-agonist use compared to controls. In confounder-adjusted regression
      models, TNF-alpha >= 6 pg/mL predicted both GERD and BE. GERD was also predicted
      by C-peptide >= 360 pg/mL, while BE was predicted by fractalkine >= 250 pg/mL and
      IP-10 >= 290 pg/mL. Finally, participants with GERD had significantly increased
      use of short-acting beta-agonist compared to controls. Overall, biomarkers
      sampled prior to GERD/BE presentation showed strong predictive abilities of
      disease development. This study frames future investigations to further our
      understanding of aerodigestive pathology due to particulate matter exposure.

PMID- 29449670
TI  - Social inhibition and behavioural flexibility when the context changes: a
      comparison across six primate species.
AB  - The ability to inhibit previously employed strategies and flexibly adjust
      behavioural responses to external conditions may be critical for individual
      survival. However, it is unclear which factors predict their distribution across
      species. Here, we investigated social inhibition and behavioural flexibility in
      six primate species (chimpanzees, bonobos, orangutans, gorillas, capuchin monkeys
      and spider monkeys) differing in terms of phylogenetic relatedness, foraging
      ecology and social organization. Depending on the social context, individuals
      could maximize their food intake by inhibiting the selection of a larger food
      reward in one condition (i.e. inhibition), but not in others, which required them
      to flexibly switching strategies across conditions (i.e. behavioural
      flexibility). Overall, our study revealed inter-specific differences in social
      inhibition and behavioural flexibility, which partially reflected differences in
      fission-fusion dynamics. In particular, orangutans and chimpanzees showed the
      highest level of inhibitory skills, while gorillas and capuchin monkeys showed
      the lowest one. In terms of behavioural flexibility, orangutans and spider
      monkeys were the best performers, while bonobos and capuchin monkeys were the
      worst ones. These results contribute to our understanding that inhibition and
      behavioural flexibility may be linked in more complex ways than usually thought,
      although both abilities play a crucial role in efficient problem solving.

PMID- 29449671
TI  - Identification of juvenility-associated genes in the mouse hepatocytes and
      cardiomyocytes.
AB  - Young individuals possess distinct properties that adults do not. The juvenile
      animals show higher activities for growth, healing, learning and plasticity than
      adults. The machinery for establishing these juvenile properties is not fully
      understood. To better understand the molecular constituents for the above
      properties, we performed a comprehensive transcriptome analysis of differently
      aged cells of mice by high-throughput sequencing and identified the genes
      selectively highly expressed in the young cells. These genes, collectively called
      as juvenility-associated genes (JAGs), show significant enrichments in the
      functions such as alternative splicing, phosphorylation and extracellular matrix
      (ECM). This implies the juvenescence might be achieved by these functions at the
      cell level. The JAG mutations are associated with progeria syndromes and growth
      disorders. Thus, the JAGs might organize the juvenile property of young animals
      and analysis of JAGs may provide scientific and therapeutic approaches toward
      treating the genetic diseases.

PMID- 29449672
TI  - Electromagnetically induced polarization grating.
AB  - Based on electromagnetically induced transparency (EIT), we investigate an all
      optical grating structure to realize polarization-dependent multiple beam
      splitting in the Raman-Nath limit. To optimize the grating performance, higher
      excited state [e.g., nS1/2 (n >= 6)] of ultracold 87Rb atoms is employed to
      construct a five-level Xi-Lambda system sharing one common populated ground
      state. A principal advantage of our proposed scheme is that the sigma+/-
      components of a linearly polarized weak probe field can be decoupled and thus be
      independently diffracted with high efficiency in both one and two dimensions by
      exploiting different quasi-standing waves as the two strong coupling fields in
      the Xi and Lambda configurations. Such an all-optical polarization-sensitive
      operation could greatly enhance the tunability and capacity of all-optical
      multiplexing, interconnecting, and networking in free space for both classical
      and quantum applications.

PMID- 29449674
TI  - Reply to 'Comment on 'Prognostic biomarkers for oral tongue squamous cell
      carcinoma: a systematic review and meta-analysis".

PMID- 29449673
TI  - The predictive and prognostic potential of plasma telomerase reverse
      transcriptase (TERT) RNA in rectal cancer patients.
AB  - BACKGROUND: Preoperative chemoradiotherapy (CRT) followed by surgery is the
      standard care for locally advanced rectal cancer, but tumour response to CRT and
      disease outcome are variable. The current study aimed to investigate the
      effectiveness of plasma telomerase reverse transcriptase (TERT) levels in
      predicting tumour response and clinical outcome. METHODS: 176 rectal cancer
      patients were included. Plasma samples were collected at baseline (before
      CRT=T0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2),
      and 4-8 months after surgery (T3) time points. Plasma TERT mRNA levels and total
      cell-free RNA were determined using real-time PCR. RESULTS: Plasma levels of TERT
      were significantly lower at T2 (P<0.0001) in responders than in non-responders.
      Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels
      independently predicted tumour response, and the prediction model had an area
      under curve of 0.80 (95% confidence interval (CI) 0.73-0.87). Multiple analysis
      demonstrated that patients with detectable TERT levels at T2 and T3 time points
      had a risk of disease progression 2.13 (95% CI 1.10-4.11)-fold and 4.55 (95% CI
      1.48-13.95)-fold higher, respectively, than those with undetectable plasma TERT
      levels. CONCLUSIONS: Plasma TERT levels are independent markers of tumour
      response and are prognostic of disease progression in rectal cancer patients who
      undergo neoadjuvant therapy.

PMID- 29449675
TI  - Comment on 'Prognostic biomarkers for oral tongue squamous cell carcinoma: a
      systematic review and meta-analysis'.

PMID- 29449676
TI  - The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial
      of a complex intervention to reduce time to diagnosis in rural cancer patients in
      Western Australia.
AB  - This corrects the article DOI: 10.1038/bjc.2017.310.

PMID- 29449677
TI  - USP35 regulates mitotic progression by modulating the stability of Aurora B.
AB  - Although approximately 100 deubiquitinating enzymes (DUBs) are encoded in the
      human genome, very little is known about the DUBs that function in mitosis. Here,
      we demonstrate that DUB USP35 functions as a mitotic regulator by controlling the
      protein levels and downstream signaling of Aurora B and the depletion of USP35
      eventually leads to several mitotic defects including cytokinesis failures. USP35
      binds to and deubiquitinates Aurora B, and inhibits the APCCDH1-mediated
      proteasomal degradation of Aurora B, thus maintaining its steady-state levels
      during mitosis. In addition, the loss of USP35 decreases the phosphorylation of
      histone H3-Ser10, an Aurora B substrate. Finally, the transcription factor FoxM1
      promotes the expression of USP35, as well as that of Aurora B, during the cell
      cycle. Our findings suggest that USP35 regulates the stability and function of
      Aurora B by blocking APCCDH1-induced proteasomal degradation, thereby controlling
      mitotic progression.

PMID- 29449678
TI  - Cytoskeleton stability is essential for the integrity of the cerebellum and its
      motor- and affective-related behaviors.
AB  - The cerebellum plays a key role in motor tasks, but its involvement in cognition
      is still being considered. Although there is an association of different
      psychiatric and cognitive disorders with cerebellar impairments, the lack of time
      course studies has hindered the understanding of the involvement of cerebellum in
      cognitive and non-motor functions. Such association was here studied using the
      Purkinje Cell Degeneration mutant mouse, a model of selective and progressive
      cerebellar degeneration that lacks the cytosolic carboxypeptidase 1 (CCP1). The
      effects of the absence of this enzyme on the cerebellum of mutant mice were
      analyzed both in vitro and in vivo. These analyses were carried out
      longitudinally (throughout both the pre-neurodegenerative and neurodegenerative
      stages) and different motor and non-motor tests were performed. We demonstrate
      that the lack of CCP1 affects microtubule dynamics and flexibility, defects that
      contribute to the morphological alterations of the Purkinje cells (PCs), and to
      progressive cerebellar breakdown. Moreover, this degeneration led not only to
      motor defects but also to gradual cognitive impairments, directly related to the
      progression of cellular damage. Our findings confirm the cerebellar implication
      in non-motor tasks, where the formation of the healthy, typical PCs structure is
      necessary for normal cognitive and affective behavior.

PMID- 29449679
TI  - TERT promoter mutation in adult granulosa cell tumor of the ovary.
AB  - The telomerase reverse transcriptase (TERT) gene is highly expressed in stem
      cells and silenced upon differentiation. Cancer cells can attain immortality by
      activating TERT to maintain telomere length and telomerase activity, which is a
      crucial step of tumorigenesis. Two somatic mutations in the TERT promoter (C228T;
      C250T) have been identified as gain-of-function mutations that promote
      transcriptional activation of TERT in multiple cancers, such as melanoma and
      glioblastoma. A recent study investigating TERT promoter mutations in ovarian
      carcinomas found C228T and C250T mutations in 15.9% of clear cell carcinomas.
      However, it is unknown whether these mutations are frequent in other ovarian
      cancer subtypes, in particular, sex cord-stromal tumors including adult granulosa
      cell tumors. We performed whole-genome sequencing on ten adult granulosa cell
      tumors with matched normal blood and identified a TERT C228T promoter mutation in
      50% of tumors. We found that adult granulosa cell tumors with mutated TERT
      promoter have increased expression of TERT mRNA and exhibited significantly
      longer telomeres compared to those with wild-type TERT promoter. Extension cohort
      analysis using allelic discrimination revealed the TERT C228T mutation in 51 of
      229 primary adult granulosa cell tumors (22%), 24 of 58 recurrent adult granulosa
      cell tumors (41%), and 1 of 22 other sex cord-stromal tumors (5%). There was a
      significant difference in overall survival between patients with TERT C228T
      promoter mutation in the primary tumors and those without it (p = 0.00253, log
      rank test). In seven adult granulosa cell tumors, we found the TERT C228T
      mutation present in recurrent tumors and absent in the corresponding primary
      tumor. Our data suggest that TERT C228T promoter mutations may have an important
      role in progression of adult granulosa cell tumors.

PMID- 29449680
TI  - PD-L1 expression in inflammatory myofibroblastic tumors.
AB  - Inflammatory myofibroblastic tumor is a rare mesenchymal tumor occurring at many
      anatomic sites, with a predilection for children and young adults. Often
      indolent, they can be locally aggressive and can metastasize, resulting in
      significant morbidity and mortality. Therapeutic options are often limited. The
      identification of underlying kinase mutations has allowed the use of targeted
      therapy in a subset of patients. Unfortunately, not all tumors harbor mutations
      and resistance to tyrosine kinase inhibitor therapy is a potential problem. We
      hypothesized that these tumors may be amenable to PD-L1 therapy given the immune
      nature of the tumor. PD-L1 expression in inflammatory myofibroblastic tumors has
      not yet been defined. The purpose of this study was to explore PD-L1 expression
      in inflammatory myofibroblastic tumors, as adaptive PD-L1 expression is known to
      enrich for response to anti-PD-1/PD-L1 therapies. Expression of PD-L1 (clone
      SP142) was assessed in 35 specimens from 28 patients. Positivity was defined as
      membranous expression in >=5% of cells and evaluated separately in tumor and
      immune cells. Adaptive vs. constitutive patterns of tumor cell PD-L1 expression
      were assessed. PD-L1 status was correlated with clinicopathologic features. CD8+
      T cell infiltrates were quantified by digital image analysis. ALK status was
      assessed by immunohistochemistry and/or FISH. Twenty-four (69%) tumors had PD
      L1(+) tumor cells and 28 (80%) showed PD-L1(+) immune cells. Most recurrent and
      metastatic tumors (80%) and ALK(-) tumors (88%) were PD-L1(+). Adaptive PD-L1
      expression was present in 23 (96%) of PD-L1(+) tumors, which also showed a three
      four fold increase in CD8+ T cell infiltration relative to PD-L1(-) tumors.
      Constitutive PD-L1 expression was associated with larger tumor size (p = 0.002).
      Inflammatory myofibroblastic tumors show frequent constitutive and adaptive PD-L1
      expression, the latter of which is thought to be predictive of response to anti
      PD-1. These data support further investigation into PD-1/PD-L1 blockade in this
      tumor type.

PMID- 29449681
TI  - Secondary Philadelphia chromosome acquired during therapy of acute leukemia and
      myelodysplastic syndrome.
AB  - The Philadelphia chromosome resulting from t(9;22)(q34;q11.2) or its variants is
      a defining event in chronic myeloid leukemia. It is also observed in several
      types of de novo acute leukemia, commonly in B lymphoblastic leukemia, and rarely
      in acute myeloid leukemia, acute leukemia of ambiguous lineage, and T
      lymphoblastic leukemia. Acquisition of the Philadelphia chromosome during therapy
      of acute leukemia and myelodysplastic syndrome is rare. We reported 19 patients,
      including 11 men and 8 women with a median age of 53 years at initial diagnosis.
      The diagnoses at initial presentation were acute myeloid leukemia (n = 11),
      myelodysplastic syndrome (n = 5), B lymphoblastic leukemia (n = 2), and T
      lymphoblastic leukemia (n = 1); no cases carried the Philadelphia chromosome. The
      Philadelphia chromosome was detected subsequently at relapse, or at refractory
      stage of acute leukemia or myelodysplastic syndrome. Of 14 patients evaluated for
      the BCR-ABL1 transcript subtype, 12 had the e1a2 transcript. In 11 of 14
      patients, the diseases before and after emergence of the Philadelphia chromosome
      were clonally related by karyotype or shared gene mutations. Of 15 patients with
      treatment information available, 7 received chemotherapy alone, 5 received
      chemotherapy plus tyrosine kinase inhibitors, 2 received tyrosine kinase
      inhibitors only, and 1 patient was not treated. Twelve patients had follow-up
      after acquisition of the Philadelphia chromosome; all had persistent/refractory
      acute leukemia. Thirteen of 15 patients died a median of 3 months after the
      emergence of the Philadelphia chromosome. In summary, secondary Philadelphia
      chromosome acquired during therapy is rare, and is associated with the e1a2
      transcript subtype, terminal disease stage, and poor outcome.

PMID- 29449682
TI  - Anatomic and terminological description and processing of breast pathologic
      specimens from oncoplastic large volume displacement surgeries.
AB  - Oncoplastic surgery provides breast cancer patients with greater aesthetic
      satisfaction without compromising disease-free survival or overall survival rate.
      Large volume displacement oncoplastic surgical techniques have become
      increasingly popular as a strategy for improving aesthetic outcomes and extending
      the option of breast conservation therapy. They often involve breast reduction or
      mastopexy reconstructive techniques to facilitate resection of large breast
      volumes on the side of the breast cancer and accompanied with symmetry
      contralateral breast reductions or mastopexies. However, dissection of large
      volume displacement oncoplastic surgical specimens presents unique challenges.
      Compared with traditional mastectomy specimens, they are relatively complicated,
      which requires the pathologist to understand the surgical procedure and the
      anatomy of the specimens. Given this, we introduce the standard anatomical and
      terminological description for the breast pathologic specimens of five large
      volume displacement oncoplastic surgical techniques commonly performed in our
      institution for breast cancer management. The individual surgical specimen is
      composed of one or several components, which include lateral wall, superior
      keyhole, medial wall, lateral wing, inferior pole, and medial wing. We also
      present specimen documentation and sectioning procedures used in our institution.
      The advantages for the patient provided by large volume reduction oncoplastic
      surgery must be supported by proper evaluation of the surgical pathology
      specimen. Therefore, we recommend that each section taken from the oncoplastic
      specimen be labeled as to its specific location in the specimen components.
      Standardized nomenclature and technique will assist pathologists in accurately
      evaluating the surgical margins.

PMID- 29449683
TI  - Adult T-cell leukemia/lymphoma can be indistinguishable from other more common T
      cell lymphomas. The University of Miami experience with a large cohort of cases.
AB  - Adult T-cell leukemia/lymphoma, an aggressive T-cell neoplasm, is causally linked
      to human T-cell lymphotropic virus type 1 and based on this association has a
      distinct geographic distribution. In our United States-based practice, whose
      population is enriched for immigrants from human T-cell lymphotropic virus type 1
      endemic areas, we have identified that a subset of adult T-cell
      leukemia/lymphoma, in the absence of human T-cell lymphotropic virus type 1
      identification, are indistinguishable from other more common T-cell neoplasms. We
      retrospectively gathered serology results for anti-human T-cell lymphotropic
      virus type 1/2 antibody in patients diagnosed with T-cell neoplasms at our
      institution. A total of 220 human T-cell lymphotropic virus type 1/2 positive
      patients with T-cell neoplasms were identified; 199 (91%) were correctly
      classified as adult T-cell leukemia/lymphoma or provisionally as peripheral T
      cell lymphoma (serology testing pending). Twenty-one cases (9%) were initially
      misclassified, including the following: 13 presenting with skin +/- peripheral
      blood involvement and misclassified as mycosis fungoides/Sezary syndrome; 7 with
      lymphomatous disease, absence of leukemic involvement, and diffuse CD30
      expression, misclassified as ALK- negative anaplastic large-cell lymphoma; 1
      thought to represent T-prolymphocytic leukemia with TCL-1 gene rearrangement and
      diffuse marrow involvement. We also present an example of adult T-cell
      leukemia/lymphoma, which mimicked lymphoepithelioid variant of peripheral T-cell
      lymphoma also with diffuse marrow involvement. A subset of adult T-cell
      leukemia/lymphoma can closely mimic a variety of other more common T-cell
      neoplasms. Due to its extreme clinicopathologic heterogeneity, identification of
      adult T-cell leukemia/lymphoma requires a high level of suspicion based on
      patient demographic alone, which should prompt anti-human T-cell lymphotropic
      virus type 1/2 serology testing in all T-cell neoplasms developing in patients of
      appropriate demographic. Absence of high level of suspicion, adult T-cell
      leukemia/lymphoma is easily misclassified.

PMID- 29449684
TI  - Fibroepithelial lesions of the breast: a comprehensive morphological and outcome
      analysis of a large series.
AB  - Mammary fibroepithelial lesions encompass a wide spectrum of tumors ranging from
      an indolent fibroadenoma to potentially fatal malignant phyllodes tumor. The
      criteria used for their classification based on morphological assessment are
      often challenging to apply and there is no consensus as to what constitutes an
      adequate resection margin. We studied a retrospective cohort of 213
      fibroepithelial lesions in 178 patients (80 fibroadenomas with unusual features
      and 133 phyllodes tumors: 63 benign, 41 borderline, and 29 malignant) in order to
      describe the spectrum of changes within each group, with special emphasis on
      margin evaluation. Outcome data were available for 153 fibroepithelial lesions in
      139 patients (median 56 months, range 3-249 months). Positive final margin (tumor
      transected), age < 50 years and a predominantly myxoid stroma were statistically
      significant predictors of local recurrence, while age > 50, stromal overgrowth,
      diffuse marked atypia, necrosis and mitotic index of >= 10 per 10 HPF were
      predictive of distant metastases. Tumors with satellite/bulging nodules were at a
      significantly higher risk to have a final positive resection margin. Our findings
      highlight important aspects of the interpretation and reporting of
      fibroepithelial lesions: the amount of myxoid stroma and the presence of
      satellite nodules are clinically relevant and should be routinely assessed and
      reported; infiltrative border might not be a prerequisite for the diagnosis of
      malignant phyllodes tumor, while the presence of tumor necrosis, massive stromal
      overgrowth or mitotic index of >= 25 per 10 HPF is diagnostic of malignant
      phyllodes tumor. On the other hand, increased mitotic index outside of the range
      of the World Health Organization guidelines in the absence of other worrisome
      features should be treated with caution, as it can be found in benign tumors.

PMID- 29449685
TI  - Cross-cultural adaptation and validation of the "Spinal Cord Injury-Falls Concern
      Scale" in the Italian population.
AB  - STUDY DESIGN: Psychometrics study. OBJECTIVE: The objective of this study was to
      develop an Italian version of the Spinal Cord Injury-Falls Concern Scale (SCI
      FCS) and examine its reliability and validity. SETTING: Multicenter study in
      spinal units in Northern and Southern Italy. The scale also was administered to
      non-hospitalized outpatient clinic patients. METHODS: The original scale was
      translated from English to Italian using the "Translation and Cultural Adaptation
      of Patient-Reported Outcomes Measures" guidelines. The reliability and validity
      of the culturally adapted scale were assessed following the "Consensus-Based
      Standards for the Selection of Health Status Measurement Instruments" checklist.
      The SCI-FCS-I internal consistency, inter-rater, and intra-rater reliability were
      examined using Cronbach's alpha coefficient and the intraclass correlation
      coefficient, respectively. Concurrent validity was evaluated using Pearson's
      correlation coefficient with the Italian version of the short form of the
      Wheelchair Use Confidence Scale for Manual Wheelchair Users (WheelCon-M-I-short
      form). RESULTS: The Italian version of the SCI-FCS-I was administered to 124
      participants from 1 June to 30 September 2017. The mean +/- SD of the SCI-FCS-I
      score was 16.73 +/- 5.88. All SCI-FCS items were either identical or similar in
      meaning to the original version's items. Cronbach's alpha was 0.827 (p < 0.01),
      the inter-rater reliability was 0.972 (p < 0.01), and the intra-rater reliability
      was 0.973 (p < 0.01). Pearson's correlation coefficient of the SCI-FCS-I scores
      with the WheelCon-M-I-short form was 0.56 (p < 0.01). CONCLUSIONS: The SCI-FCS-I
      was found to be reliable and a valid outcome measure for assessing manual
      wheelchair concerns about falling in the Italian population.

PMID- 29449686
TI  - Impact of genetically engineered maize on agronomic, environmental and
      toxicological traits: a meta-analysis of 21 years of field data.
AB  - Despite the extensive cultivation of genetically engineered (GE) maize and
      considerable number of scientific reports on its agro-environmental impact, the
      risks and benefits of GE maize are still being debated and concerns about safety
      remain. This meta-analysis aimed at increasing knowledge on agronomic,
      environmental and toxicological traits of GE maize by analyzing the peer-reviewed
      literature (from 1996 to 2016) on yield, grain quality, non-target organisms
      (NTOs), target organisms (TOs) and soil biomass decomposition. Results provided
      strong evidence that GE maize performed better than its near isogenic line: grain
      yield was 5.6 to 24.5% higher with lower concentrations of mycotoxins (-28.8%),
      fumonisin (-30.6%) and thricotecens (-36.5%). The NTOs analyzed were not affected
      by GE maize, except for Braconidae, represented by a parasitoid of European corn
      borer, the target of Lepidoptera active Bt maize. Biogeochemical cycle parameters
      such as lignin content in stalks and leaves did not vary, whereas biomass
      decomposition was higher in GE maize. The results support the cultivation of GE
      maize, mainly due to enhanced grain quality and reduction of human exposure to
      mycotoxins. Furthermore, the reduction of the parasitoid of the target and the
      lack of consistent effects on other NTOs are confirmed.

PMID- 29449687
TI  - Reproductive endocrinology: Postmenopausal hormone therapy to prevent chronic
      conditions.

PMID- 29449688
TI  - Obesity: Early severe obesity in children.

PMID- 29449690
TI  - Diabetes: Clinical markers of glycaemic response to DPP4 inhibitor therapy.

PMID- 29449689
TI  - Current and emerging therapies for PNETs in patients with or without MEN1.
AB  - Pancreatic neuroendocrine tumours (PNETs) might occur as a non-familial isolated
      endocrinopathy or as part of a complex hereditary syndrome, such as multiple
      endocrine neoplasia type 1 (MEN1). MEN1 is an autosomal dominant disorder
      characterized by the combined occurrence of PNETs with tumours of the
      parathyroids and anterior pituitary. Treatments for primary PNETs include
      surgery. Treatments for non-resectable PNETs and metastases include biotherapy
      (for example, somatostatin analogues, inhibitors of receptors and monoclonal
      antibodies), chemotherapy and radiological therapy. All these treatments are
      effective for PNETs in patients without MEN1; however, there is a scarcity of
      clinical trials reporting the efficacy of the same treatments of PNETs in
      patients with MEN1. Treatment of PNETs in patients with MEN1 is challenging owing
      to the concomitant development of other tumours, which might have metastasized.
      In recent years, preclinical studies have identified potential new therapeutic
      targets for treating MEN1-associated neuroendocrine tumours (including PNETs),
      and these include epigenetic modification, the beta-catenin-wingless (WNT)
      pathway, Hedgehog signalling, somatostatin receptors and MEN1 gene replacement
      therapy. This Review discusses these advances.

PMID- 29449691
TI  - Enhanced release of acid sphingomyelinase-enriched exosomes generates a
      lipidomics signature in CSF of Multiple Sclerosis patients.
AB  - Multiple Sclerosis (MuS) is a complex multifactorial neuropathology, resulting in
      heterogeneous clinical presentation. A very active MuS research field concerns
      the discovery of biomarkers helpful to make an early and definite diagnosis. The
      sphingomyelin pathway has emerged as a molecular mechanism involved in MuS, since
      high levels of ceramides in cerebrospinal fluid (CSF) were related to axonal
      damage and neuronal dysfunction. Ceramides are the hydrolysis products of
      sphingomyelins through a reaction catalyzed by a family of enzymes named
      sphingomyelinases, which were recently related to myelin repair in MuS. Here,
      using a lipidomic approach, we observed low levels of several sphingomyelins in
      CSF of MuS patients compared to other inflammatory and non-inflammatory, central
      or peripheral neurological diseases. Starting by this result, we investigated the
      sphingomyelinase activity in CSF, showing a significantly higher enzyme activity
      in MuS. In support of these results we found high number of total exosomes in CSF
      of MuS patients and a high number of acid sphingomyelinase-enriched exosomes
      correlated to enzymatic activity and to disease severity. These data are of
      diagnostic relevance and show, for the first time, high number of acid
      sphingomyelinase-enriched exosomes in MuS, opening a new window for therapeutic
      approaches/targets in the treatment of MuS.

PMID- 29449692
TI  - The deubiquitinase USP9X promotes tumor cell survival and confers chemoresistance
      through YAP1 stabilization.
AB  - The Yes-associated protein 1 (YAP1), a major downstream effector of the Hippo
      pathway, functions as a transcriptional regulator and has an important role in
      cellular control of organ size and tumor growth. Elevated oncogenic activity of
      YAP1 has been clarified in different types of human cancers, which contributes to
      cancer cell survival and chemoresistance. However, the molecular mechanism of
      YAP1 overexpression in cancer is still not clear. Here we demonstrate that the
      deubiquitination enzyme USP9X deubiquitinates and stabilizes YAP1, thereby
      promoting cancer cell survival. Increased USP9X expression correlates with
      increased YAP1 protein in human breast cancer cell lines and patient samples.
      Moreover, depletion of USP9X increases YAP1 polyubiquitination, which in turn
      elevates YAP1 turnover and cell sensitivity to chemotherapy. Overall, our study
      establishes the USP9X-YAP1 axis as an important regulatory mechanism of breast
      cancer and provides a rationale for potential therapeutic interventions in the
      treatment of breast cancer.

PMID- 29449693
TI  - Tumor cell-intrinsic Tim-3 promotes liver cancer via NF-kappaB/IL-6/STAT3 axis.
AB  - T-cell immunoglobulin and mucin-domain containing-3 (Tim-3), mediating immune
      exhaustion in tumor microenvironment, has become a promising target for tumor
      therapy. However, the exact mechanisms for tumor cell-intrinsic Tim-3 in tumor
      development and its potential contribution in Tim-3-targeted therapy strategy
      have not been elucidated yet. In this study, we showed that human liver cancer
      tissues contained high ratio of Tim-3-expressing hepatocytes, and cytokines rich
      in tumor microenvironment and HBV involved in Tim-3 upregulation in malignant
      hepatocytes. We demonstrated that hepatocyte-specific Tim-3 overexpression
      enhances tumor cell growth, whereas Tim-3 inhibition on malignant hepatocytes by
      anti-Tim-3 antibodies or RNAi suppresses tumor growth both in vitro and in Tim-3
      knockout mice. Mechanistically, the hepatocyte-Tim-3 receptor activates NF-kappaB
      phosphorylation, which in turn stimulates IL-6 secretion and STAT3
      phosphorylation. Our results identify tumor cell-intrinsic functions of Tim-3 in
      tumorigenesis and suggest that blocking Tim-3 in tumor cells might contribute to
      the clinical efficacy of anti-Tim-3 antibody treatment in the future tumor
      therapy.

PMID- 29449694
TI  - Interaction between STAT3 and GLI1/tGLI1 oncogenic transcription factors promotes
      the aggressiveness of triple-negative breast cancers and HER2-enriched breast
      cancer.
AB  - Signal transducer and activator of transcription 3 (STAT3), glioma oncogene
      homolog 1 (GLI1), and truncated GLI1 (tGLI1) are oncogenic transcription factors
      playing important roles in breast cancer. tGLI1 is a gain-of-function GLI1
      isoform. Whether STAT3 physically and/or functionally interacts with GLI1/tGLI1
      has not been explored. To address this knowledge gap, we analyzed 47 node
      positive breast cancer specimens using immunohistochemical staining and found
      that phosphorylated-STAT3 (Y705), GLI1, and tGLI1 are co-overexpressed in the
      majority of triple-negative breast carcinomas (64%) and HER2-enriched (68%)
      breast carcinomas, and in lymph node metastases (65%). Using gene set enrichment
      analysis, we analyzed 710 breast tumors and found that STAT3 activation and
      GLI1/tGLI1 activation signatures are co-enriched in triple-negative subtypes of
      breast cancers and HER2-enriched subtypes of breast cancers, but not in luminal
      subtypes of breast cancers. Patients with high levels of STAT3 and GLI1/tGLI1 co
      activation in their breast tumors had worse metastasis-free survival compared to
      those with low levels. Since these proteins co-overexpress in breast tumors, we
      examined whether they form complexes and observed that STAT3 interacted with both
      GLI1 and tGLI1. We further found that the STAT3-GLI1 and STAT3-tGLI1 complexes
      bind to both consensus GLI1-binding and STAT3-binding sites using chromatin
      immunoprecipitation (ChIP) assay, and that the co-overexpression markedly
      activated a promoter controlled by GLI1-binding sites. To identify genes that can
      be directly co-activated by STAT3 and GLI1/tGLI1, we analyzed three ChIP-seq
      datasets and identified 34 potential target genes. Following validations using
      reverse transcription polymerase chain reaction and survival analysis, we
      identified three genes as novel transcriptional targets of STAT3 and GLI1/tGLI1,
      R-Ras2, Cep70, and UPF3A. Finally, we observed that co-overexpression of STAT3
      with GLI1/tGLI1 promoted the ability of breast cancer cells to form mammospheres
      and that STAT3 only cooperates with tGLI1 in immortalized mammary epithelial
      cells. In summary, our study identified novel physical and functional cooperation
      between two families of oncogenic transcription factors, and the interaction
      contributes to aggressiveness of breast cancer cells and poor prognosis of triple
      negative breast cancers and HER2-enriched breast cancers.

PMID- 29449695
TI  - Arresting of miR-186 and releasing of H19 by DDX43 facilitate tumorigenesis and
      CML progression.
AB  - Cancer-testis (CT) antigens, rarely in normal tissues except testis, are
      expressed in many tumor types. In recent years, DDX43 has been shown to be
      expressed in several malignancies. However, the role of DDX43 during
      tumorigenesis is not well established. In the present study, we explored the
      function of DDX43 in chronic myeloid leukemia (CML). We found that DDX43
      overexpression in CML cell lines enhanced survival and colony formation,
      inhibited cell apoptosis, promoted tumorigenesis, and CML progression. In
      contrast, silencing of DDX43 inhibited cell survival and tumorigenesis.
      Upregulated H19 and downregulated miR-186 were identified in DDX43-transfected
      cells. Furthermore, we demonstrated that miR-186 targeted DDX43, and
      overexpressed miR-186 increased apoptosis and decreased cell survival. We also
      showed that DDX43 regulated the expression of H19 through demethylation and
      silencing H19 inhibited cell survival. Taken together, these results indicate
      that DDX43 provides critical support to the progression of CML by enhancing cell
      survival, colony formation, and inhibiting cell apoptosis, thereby implicating
      DDX43 as a potential therapeutic target in CML.

PMID- 29449698
TI  - Migraine: Migraine - a risk factor for cardiovascular disease?

PMID- 29449697
TI  - Stereochemical identification of glucans by oligothiophenes enables cellulose
      anatomical mapping in plant tissues.
AB  - Efficient use of plant-derived materials requires enabling technologies for non
      disruptive composition analysis. The ability to identify and spatially locate
      polysaccharides in native plant tissues is difficult but essential. Here, we
      develop an optical method for cellulose identification using the structure
      responsive, heptameric oligothiophene h-FTAA as molecular fluorophore.
      Spectrophotometric analysis of h-FTAA interacting with closely related glucans
      revealed an exceptional specificity for beta-linked glucans. This optical, non
      disruptive method for stereochemical differentiation of glycosidic linkages was
      next used for in situ composition analysis in plants. Multi-laser/multi-detector
      analysis developed herein revealed spatial localization of cellulose and
      structural cell wall features such as plasmodesmata and perforated sieve plates
      of the phloem. Simultaneous imaging of intrinsically fluorescent components
      revealed the spatial relationship between cell walls and other organelles, such
      as chloroplasts and lignified annular thickenings of the trachea, with precision
      at the sub-cellular scale. Our non-destructive method for cellulose
      identification lays the foundation for the emergence of anatomical maps of the
      chemical constituents in plant tissues. This rapid and versatile method will
      likely benefit the plant science research fields and may serve the biorefinery
      industry as reporter for feedstock optimization as well as in-line monitoring of
      cellulose reactions during standard operations.

PMID- 29449696
TI  - Snail regulates BMP and TGFbeta pathways to control the differentiation status of
      glioma-initiating cells.
AB  - Glioblastoma multiforme is a brain malignancy characterized by high
      heterogeneity, invasiveness, and resistance to current therapies, attributes
      related to the occurrence of glioma stem cells (GSCs). Transforming growth factor
      beta (TGFbeta) promotes self-renewal and bone morphogenetic protein (BMP) induces
      differentiation of GSCs. BMP7 induces the transcription factor Snail to promote
      astrocytic differentiation in GSCs and suppress tumor growth in vivo. We
      demonstrate that Snail represses stemness in GSCs. Snail interacts with SMAD
      signaling mediators, generates a positive feedback loop of BMP signaling and
      transcriptionally represses the TGFB1 gene, decreasing TGFbeta1 signaling
      activity. Exogenous TGFbeta1 counteracts Snail function in vitro, and in vivo
      promotes proliferation and re-expression of Nestin, confirming the importance of
      TGFB1 gene repression by Snail. In conclusion, novel insight highlights
      mechanisms whereby Snail differentially regulates the activity of the opposing
      BMP and TGFbeta pathways, thus promoting an astrocytic fate switch and repressing
      stemness in GSCs.

PMID- 29449699
TI  - Alzheimer disease: Blood amyloid-beta successfully signals AD.

PMID- 29449701
TI  - Immunotherapy: Direct shot.

PMID- 29449702
TI  - Tumour immunology: NK cells bring in the troops.

PMID- 29449703
TI  - Microbiota: Pathobiont peacekeepers.

PMID- 29449704
TI  - Pleiotropic effects of calcium channel blockers.

PMID- 29449700
TI  - Imaging tau and amyloid-beta proteinopathies in Alzheimer disease and other
      conditions.
AB  - Most neurodegenerative disorders are associated with aggregated protein deposits.
      In the case of Alzheimer disease (AD), extracellular amyloid-beta (Abeta)
      aggregates and intracellular tau neurofibrillary tangles are the two
      neuropathological hallmarks of the disease. Abeta-PET imaging has already been
      approved for clinical use and is being used in clinical trials of anti-Abeta
      therapies both for patient recruitment and as an outcome measure. These studies
      have shown that Abeta accumulation is a protracted process that can extend for
      more than 2 decades before the onset of clinical AD. This Review describes how in
      vivo brain imaging of Abeta pathology has revolutionized the evaluation of
      patients with clinical AD by providing robust and reproducible statements of
      global or regional brain Abeta burden and enabling the monitoring of disease
      progression. The role of selective tau imaging is discussed, focusing on how
      longitudinal tau and Abeta imaging studies might reveal the various effects
      (sequential and/or parallel, independent and/or synergistic) of these proteins on
      progression, cognition and other disease-specific biomarkers of
      neurodegeneration. Finally, imaging studies are discussed in the context of
      elucidating the respective roles of Abeta and tau in AD and in advancing our
      understanding of the relationship and/or interplay between these two
      proteinopathies.

PMID- 29449705
TI  - Comparison between L-type and N/L-type calcium channel blockers in the regulation
      of home blood-pressure variability in elderly hypertensive patients.
AB  - Recent studies suggest that L-type calcium channel blockers (CCBs) contribute to
      reducing blood pressure (BP) variability. We investigated whether inhibition of
      the N-type calcium channel has an additional effect on BP variability by
      comparing the effect of L-type and L/N-type CCBs on home BP variability in
      elderly hypertensive patients. Twenty-six hypertensive patients (>=65 years) were
      subjected to repeated changes with the administration of amlodipine (L-type CCB)
      and cilnidipine (L/N-type CCB) every 2 months. They measured the home BP in the
      morning and evening, and the coefficient of variation (CV) was calculated. We
      measured the brachial-ankle pulse wave velocity (baPWV) and urinary catecholamine
      excretion as an index of the arterial stiffness and sympathetic nerve activity,
      respectively. There was no difference in the effect of both drugs on the CV in
      the morning and evening, while amlodipine was associated with a modestly higher
      pulse rate and lower BP than cilnidipine. By comparing individual patient data
      for the CV with each drug, we found that higher urinary catecholamine excretion
      was associated with the effectiveness of cilnidipine over amlodipine in the BP
      variability in the morning, which was not the case in the evening. In contrast,
      lower baPWV was associated with the effectiveness of amlodipine over cilnidipine
      on BP variability in the evening. Lower baPWV was also associated with lower BP
      variability in the evening. Cilnidipine has a similar capacity as amlodipine in
      reducing home BP variability, but the underlying mechanisms in reducing BP
      variability may differ.

PMID- 29449706
TI  - Pre-pregnancy endothelial dysfunction and birth outcomes: The Coronary Artery
      Risk Development in Young Adults (CARDIA) Study.
AB  - Endothelial dysfunction is a form of subclinical cardiovascular disease that may
      be involved in preterm birth and small-for-gestational-age deliveries. However,
      concentrations of biomarkers of endothelial dysfunction before pregnancy have
      rarely been measured. We hypothesized that higher levels of biomarkers of
      endothelial dysfunction (cellular adhesion molecules and selectins) would be
      associated with odds of preterm birth and/or small-for-gestational-age
      deliveries. We included 235 women from the Coronary Artery Risk Development in
      Young Adults (CARDIA) study who were nulliparous at Y7, reported >=1 live birth
      through Y25, and had >=1 biomarker measured at Y7. We tested for associations
      between individual biomarkers and an averaged z-score representing total
      endothelial dysfunction with preterm birth and/or small-for-gestational-age
      deliveries using Poisson regression, adjusted for demographic and clinical
      characteristics at the exam immediately preceding index birth. At Y7, total
      evidence of  endothelial dysfunction was similar in women who did (n = 59) and
      did not have (n = 176) preterm birth and/or small-for-gestational-age deliveries.
      There was no association between biomarkers of endothelial dysfunction (either
      individual biomarker or total score) with odds of preterm birth and/or small-for
      gestational-age deliveries after adjustment: IRR = 1.01, 95% CI: 0.74, 1.39, p =
      0.93 for total endothelial biomarker score. Associations were not modified by
      race. We conclude that biomarkers of endothelial dysfunction in nulliparous
      women, measured ~3 years before pregnancy, did not identify women at risk for
      preterm birth and/or small-for-gestational-age deliveries. This suggests that the
      maternal endothelial dysfunction that is believed to contribute to these birth
      outcomes may not be detectable before pregnancy.

PMID- 29449707
TI  - Modulation of cardiac stem cell characteristics by metoprolol in hypertensive
      heart disease.
AB  - Cardiac stem cells (CSCs) play a vital role in cardiac remodeling. Uncontrolled
      hypertension leads to cardiac hypertrophy, followed by cardiac failure.
      Pathological remodeling is associated with enhanced oxidative stress. Decreased
      cardiac stem cell efficiency is speculated in heart diseases. Maintaining a
      healthy stem cell population is essential for preventing progressive cardiac
      remodeling. Some anti-hypertensive drugs are cardioprotective. However, the
      effect of these drugs on CSCs has not been investigated. Metoprolol is a
      cardioprotective anti-hypertensive agent. To examine whether metoprolol can
      prevent the deterioration of CSC efficiency, spontaneously hypertensive rats
      (SHRs) were treated with this drug, and the effects on stem cell function were
      evaluated. Six-month-old male SHRs were treated with metoprolol (50 mg * kg-1per
      day) for 2 months. The effectiveness of the treatment at reducing blood pressure
      and reducing hypertrophy was ensured, and the animals were killed. Cardiac stem
      cells were isolated from the atrial tissue, and the effect of metoprolol on stem
      cell migration, proliferation, differentiation, and survival was evaluated by
      comparing the treated SHRs with untreated SHRs and normotensive Wistar rats.
      Compared to the Wistar rats, the SHR rats presented with a decrease in stem cell
      migration and proliferation and an increase in intracellular oxidative stress and
      senescence. Treating SHRs with metoprolol increased CSC migration and
      proliferation potential and stemness retention. Cellular senescence and oxidative
      stress were reduced. The attributes of stem cells from the metoprolol-treated
      SHRs were comparable to those of the Wistar rats. The restoration of stem cell
      efficiency is expected to prevent hypertension-induced progressive cardiac
      remodeling.

PMID- 29449708
TI  - Cancer: Reset your circadian clock.

PMID- 29449709
TI  - Cancer: Fibroblast subtype provides niche for cancer stem cells.

PMID- 29449710
TI  - Oncologists tap the microbiome in bid to improve immunotherapy outcomes.

PMID- 29449711
TI  - Cancer: New path to improving immunotherapy.

PMID- 29449714
TI  - Behavioural neuroscience: In hunt mode.

PMID- 29449713
TI  - Control of synaptic plasticity in deep cortical networks.
AB  - Humans and many other animals have an enormous capacity to learn about sensory
      stimuli and to master new skills. However, many of the mechanisms that enable us
      to learn remain to be understood. One of the greatest challenges of systems
      neuroscience is to explain how synaptic connections change to support maximally
      adaptive behaviour. Here, we provide an overview of factors that determine the
      change in the strength of synapses, with a focus on synaptic plasticity in
      sensory cortices. We review the influence of neuromodulators and feedback
      connections in synaptic plasticity and suggest a specific framework in which
      these factors can interact to improve the functioning of the entire network.

PMID- 29449716
TI  - Neuroimmunology: Dietary salt-induced deficits.

PMID- 29449712
TI  - Imaging structural and functional brain development in early childhood.
AB  - In humans, the period from term birth to ~2 years of age is characterized by
      rapid and dynamic brain development and plays an important role in cognitive
      development and risk of disorders such as autism and schizophrenia. Recent
      imaging studies have begun to delineate the growth trajectories of brain
      structure and function in the first years after birth and their relationship to
      cognition and risk of neuropsychiatric disorders. This Review discusses the
      development of grey and white matter and structural and functional networks, as
      well as genetic and environmental influences on early-childhood brain
      development. We also discuss initial evidence regarding the usefulness of early
      imaging biomarkers for predicting cognitive outcomes and risk of neuropsychiatric
      disorders.

PMID- 29449717
TI  - Reply to Brioude et al.

PMID- 29449718
TI  - Revisiting Wilms tumour surveillance in Beckwith-Wiedemann syndrome with IC2
      methylation loss, reply.

PMID- 29449715
TI  - Leptin and brain-adipose crosstalks.
AB  - Interactions between the brain and distinct adipose depots have a key role in
      maintaining energy balance, thereby promoting survival in response to metabolic
      challenges such as cold exposure and starvation. Recently, there has been renewed
      interest in the specific central neuronal circuits that regulate adipose depots.
      Here, we review anatomical, genetic and pharmacological studies on the neural
      regulation of adipose function, including lipolysis, non-shivering thermogenesis,
      browning and leptin secretion. In particular, we emphasize the role of leptin
      sensitive neurons and the sympathetic nervous system in modulating the activity
      of brown, white and beige adipose tissues. We provide an overview of advances in
      the understanding of the heterogeneity of the brain regulation of adipose tissues
      and offer a perspective on the challenges and paradoxes that the community is
      facing regarding the actions of leptin on this system.

PMID- 29449719
TI  - Incidental inequity.

PMID- 29449720
TI  - Biallelic inactivating variants in the GTPBP2 gene cause a neurodevelopmental
      disorder with severe intellectual disability.
AB  - Congenital neurological disorders are genetically highly heterogeneous. Rare
      forms of hereditary neurological disorders are still difficult to be adequately
      diagnosed. Pertinent studies, especially when reporting only single families,
      need independent confirmation. We present three unrelated families in which whole
      exome sequencing identified the homozygous non-sense variants c.430[C>T];[C>T]
      p.(Arg144*), c.1219[C>T];[C>T] p.(Gln407*) and c.1408[C>T];[C>T] p.(Arg470*) in
      GTPBP2. Their clinical presentations include early onset and apparently non
      progressive motor and cognitive impairment, and thereby overlap with findings in
      a recently described family harbouring a homozygous GTPBP2 splice site variant.
      Notable differences include structural brain abnormalities (e.g., agenesis of the
      corpus callosum, exclusive to our patients), and evidence for brain iron
      accumulation (exclusive to the previously described family). This report confirms
      pathogenicity of biallelic GTPBP2 inactivation and broadens the phenotypic
      spectrum. It also underlines that a potential involvement of brain iron
      accumulation needs clarification. Further patients will have to be identified and
      characterised in order to fully define the core features of GTPBP2-associated
      neurological disorder, but future approaches to molecular diagnosis of
      neurodevelopmental disorders should implement GTPBP2.

PMID- 29449722
TI  - Current usefulness of aspiration cytology (FNAC) in the head and neck diagnosis.
AB  - Background: Fine Needle Aspiration Cytology (FNAC) is a well established and
      widely used method for both a preliminary and sometime final non-invasive
      pathologic diagnosis. FNAC is a simple and inexpensive diagnostic tool and should
      represent the standard of care in developing and resource-poor countries while
      maintaining its diagnostic usefulness in developed and advanced ones. Methods:
      The concordance between preoperative FNAC and final histology was evaluated in
      168 patients operated on at the Otorhinolaryngology Unit, "A. Murri" Hospital,
      Fermo (Italy), from January 2012 to October 2016, including thyroid cases,
      salivary glands and cervical masses. Results: The percentages of correct
      diagnosis provided by FNAC were good in all groups of pathologies and in
      accordance with the mean data of the literature. In particular the kappa
      statistic for the degree of agreement between FNAC and definitive histology (good
      > 0.6 and excellent > 0.8) was 0.74 for the thyroid, 0.83 for the parotid and
      0.71 for both the submandibular and the cervical masses. Discussion: Thy 3 group
      is still the most challenging for a successful FNAC diagnostic prediction.
      Especially in the developed and advanced countries, both the immediate review of
      the smear with its repetition, if needed, and the aspiration performed under
      CT/MRI guidance, when necessary, seem to further empower FNAC diagnostic
      resolution and should be pursued. Being routinely used for more than 40 years,
      FNAC is still a valuable and cost-effective tool to distinguish between cases
      that don't need any treatment, cases to be treated medically and those that
      require surgical excision. In the Authors' opinion every institution should
      periodically review its data in order to monitor and assess the accuracy of its
      diagnostic activity.

PMID- 29449721
TI  - Bi-allelic inactivating variants in the COCH gene cause autosomal recessive
      prelingual hearing impairment.
AB  - Pathogenic variant in COCH are a known cause of DFNA9 autosomal dominant
      progressive hearing loss and vestibular dysfunction with adult onset. Hitherto,
      only dominant nonsynonymous variants and in-frame deletions with a presumed
      dominant negative or gain-of-function effect have been described. Here, we
      describe two brothers with congenital prelingual deafness and a homozygous
      nonsense c.292C>T(p.Arg98*) COCH variant, suggesting a loss-of-function effect.
      Vestibular dysfunction starting in the first decade was observed in the older
      patient. The heterozygous parents and sibling have normal hearing and vestibular
      function, except for the mother, who shows vestibular hyporeflexia and abnormal
      smooth pursuit tests, most likely due to concomitant disease. This is the first
      report of autosomal recessive inheritance of cochlea-vestibular dysfunction
      caused by a pathogenic variant in the COCH gene. An earlier onset of hearing
      impairment and vestibular dysfunction compared to the dominant hearing loss
      causing COCH variants is observed.

PMID- 29449723
TI  - An outbreak of cutaneous leishmaniasis in Modena province (Northern Italy):
      report of 35 cases.
AB  - Canine Leishmaniasis is a disease endemic in many parts of Europe, carried by
      insects of phlebotomous species. Humans are occasional hosts of the parasites.
      Cases of human leishmaniasis have been registered in Italy, particularly in the
      southern and coastal regions. In the period 1997-2016, we collected a series of
      35 patients affected by cutaneous leishmaniasis, uncovered by skin biopsy and
      histological examination, 21 of them found in last 3 years. The patients, 28
      males and 7 female, aged between 19 and 91, resided in a restricted area of
      Northern Italy, and none, but two, had travelled abroad. Lesions presented
      clinically mostly as single nodule or plaque, often ulcerated, and involved
      predominantly head-neck and upper extremities. Histology showed a diffuse,
      granulomatous inflammation including numerous plasma cells. Variable numbers of
      amastigotes were visible, usually in the superficial part of the dermis, in all
      cases but two. In these two cases, highly suspicious by clinico-pathologic
      features, PCR analysis allowed to achieve the correct diagnosis. Our attention
      was then focused on the geographical residence of the patients, that turned out
      to be mostly in the piedmont area, whereas only one lived in the alluvial area
      corresponding to Padana plain. These data underline the diffusion of phlebotomus
      in northern areas of Italy, and particularly on the hills, characterized by a
      type of soil more favorable to vector survival; also, they indicate the
      adaptation of leishmania to hosts other than dogs, such as foxes and small
      rodents. Histology alone resulted sufficient to make diagnosis in most cases, but
      PCR analysis is recommended in those cases showing a suspicious background, in
      absence of amastigotes.

PMID- 29449724
TI  - Angiomyofibroblastoma of the spermatic cord: a case report.
AB  - Angiomyofibroblastoma (AMF) is a rare benign mesenchymal tumor with tendency to
      arise in the lower genital tract of middleaged women, predominately in the vulva.
      A few cases of AMF in males have been reported involving the scrotum, perineum or
      spermatic cord. We report a new case of AMF arising in the right inguinal region
      of a 27-year-old man. The tumor was well-circumscribed, myxoid and measured 30 mm
      in maximum dimension. On microscopic examination, the tumor was composed of
      spindle cells without atypia and with less than one mitosis figure per 10 high
      power fields. Multinucleated cells and mast cells were observed. The stroma was
      myxoid and edematous with abundant capillary-sized blood vessels.
      Immunohistochemical staining showed a strong immunoreactivity for desmin and
      smooth muscle actin. The tumor cells were negative for estrogen receptors and
      focally positive for progesterone receptors with a low proliferative index of
      Ki67 (< 5%). This unusual neoplasm should be distinguished from aggressive
      angiomyxoma and other myxoid malignant tumors.

PMID- 29449725
TI  - Iatrogenic colorectal Kaposi's sarcoma complicating a refractory ulcerative
      colitis in a human immunodeficiency negative-virus patient.
AB  - Kaposi sarcoma is an unusual tumor associated to a human herpes virus-8 infection
      involving the skin or internal organs. Iatrogenic Kaposi's sarcoma often occurs
      in patients receiving immunosuppressive therapy. So far, a few Kaposi's sarcoma
      cases have been reported in the literature associated with inflammatory bowel
      diseases. We report a 53-year-old male diagnosed with a severe refractory
      ulcerative colitis who was treated with corticosteroids and azathioprine. The
      patient underwent a colectomy after the failure of medical treatment.
      Histological examination of the colon showed findings suggestive of Kaposi's
      sarcoma. Immunohistochemistry for human herpes virus-8 was positive in the
      colonic lesions. Correspondence.

PMID- 29449726
TI  - Primary well differentiated neuroendocrine tumor of ovary collides with Mucinous
      borderline tumor in a postmenopausal female: a report of case and review of
      literature.
AB  - Collision tumors represent a coexistence of two adjacent but histologically
      distinct tumors without histologic admixture in an organ. Primary well
      differentiated neuroendocrine tumor of ovary is rare and coexistent borderline
      mucinous tumor makes this association extremely rare. Although these tumors have
      been reported in other organs, its occurrence in ovary is rare. Collision tumor
      comprising primary neuroendocrine tumor of ovary and mucinous borderline tumor is
      an extremely rare occurrence. Here we report a case of this collision tumor in a
      postmenopausal female. H&E and immunohistochemical stains for chromogranin,
      synaptophysin, CDX-2, CK20, CK7 and Ki-67 were performed to confirm the diagnosis
      of collision tumor. Extensive search of literature revealed only a couple of
      cases report so far with this association. Our case is unique for a reason that
      we have reported trabecular variant of neuroendocrine tumor while the previously
      reported cases were insular variant. Management depends on patient's age, desire
      for fertility and disease distribution.

PMID- 29449727
TI  - Adenoid ameloblastoma with dentinoid and cellular atypia: a case report and
      literature review.
AB  - Adenomatoid odontogenic tumor (AOT) is always benign. Given the very rare
      recurrence rate and the zero potential of malignant transformation, authors have
      considered it a hamartoma. Accordingly, 'AOT' is no more than a misnomer. This
      report, however, describes the first recognition of cellular atypia and
      plemorphism in a peripheral orophayrngeal AOT which embraces an ameloblastic
      component. The overall picture was diagnosed, after careful histological and
      immunohitochemical assessment, as a peripheral adenoid ameloblastoma. This find
      may promote a new pathogenetic scenario to the nosology of this debatable lesion.

PMID- 29449728
TI  - Vaginal rhabdomyoma: a case report of an uncommon and misleading neoplasm.
AB  - Vaginal rhabdomyoma is an extremely rare tumor which presents as a vaginal
      polypoid masses. It is essential to differentiate it from benign and malignant
      mimickers so that appropriate therapy may be provided. The present report
      describes a vaginal wall nodule of a symptomatic 24-year-old woman. Local
      excision and subsequent pathological examination were performed. The final
      diagnosis was vaginal rhabdomyoma. The literature is reviewed and differential
      diagnosis are discussed.

PMID- 29449729
TI  - Parotid metastasis of renal cell carcinoma, mimicking primary clear cell
      oncocytoma: report of a case and brief review of the literature.
AB  - Malignancies of the parotid gland are relatively uncommon, accounting for only 3
      6% of all head and neck cancers. Most of them are primary neoplasms, metastases
      are uncommon. Renal cell carcinoma (RCC) represents 3% of adult malignancies, the
      clear cell type comprises up to 70% of all RCC. RCC has an unpredictable behavior
      and the unique potential to metastasize to nearly every organ in the body. Though
      not as frequent, metastatic RCC to the head and neck has been identified in the
      thyroid, salivary glands, skull base, sinuses, pharynx, tonsils, tongue, lip and
      skin. Metastasis to the parotid gland is very rare. Here, we report the case of a
      clear cell type RCC metastatic to the parotid gland and mimicking a primary clear
      cell oncocytoma. Differential diagnoses and a brief review of the literature are
      added.

PMID- 29449730
TI  - Ovarian leiomyoma with myxoid stroma.
AB  - Ovarian smooth muscle tumours are rare. Notable myxoid change in smooth muscle
      tumours is uncommon, and raises diagnostic issues that need to be considered on
      evaluating a spindle cell lesion with notable myxoid change. There is only one
      case of myxoid leiomyoma of the ovary previously reported. We here report a case
      of ovarian leiomyoma with areas of myxoid stroma and discuss the relevant
      differential diagnosis and histological features to be assessed in such a lesion.

PMID- 29449731
TI  - Mixed malignant mullerian tumor with neuroendocrine features in an irradiated
      uterus for cervical carcinoma. A unique association? A morphological,
      immunohistochemisty and ultrastructural study.
AB  - Chemo-radiation represents an effective therapy for carcinoma of the uterine
      cervix. The endometrium may however receive a consistent dose of mutagenic
      radiations and patients may have an increased risk of secondary malignancies.
      Endometrial mixed malignant mullerian tumor (MMMT) is a rare, highly aggressive
      disease, and neuroendocrine features are even rarer. A 68 years old woman
      underwent radio-chemotherapy for a squamous cell carcinoma of the cervix. Follow
      up was uneventful until, eight years after radio-chemotherapy, imaging exams
      detected a diffuse enlargement of the uterine body. Radical hysterectomy revealed
      a multiphasic lesion with both sarcomatous and mixed carcinomatous components.
      The carcinomatous, component presented neuroendocrine histologic and
      ultrastuctural features and an intense expression of neuroendocrine
      immunohistochemistry markers. No residual cervical carcinoma was documented
      (pR0). The patient died of disease after 9 months. Reported cases further
      demonstrate how the irradiation of the uterus for cervical cancer carries a not
      negligible risk of developing a second endometrial cancer. The second cancer may
      develop years after initial therapy and may have aggressive histologic and
      clinical features. This case underlines the importance for a long follow-up in
      women having received radio-chemotherapy alone.

PMID- 29449732
TI  - Gastric metastasis from cervix carcer: a case report.
AB  - Gastric metastasis by solid tumor cancer is a rare event. Concomitant metastases
      to other organs are frequent, so that this condition is often associated to a
      poor prognosis. Upper gastrointestinal bleeding and anemia are the most common
      presenting symptoms. We present the case of a 81 years old women previously
      treated for cervix carcinoma showing later a stomach metastasis. The patient is
      alive and disease free 39 months after salvage gastrectomy. A radical surgery in
      selected patients could be useful for symptom palliation and prolonged survival.

PMID- 29449733
TI  - Dedifferentiated primary mediastinal liposarcoma mimicking a thymic tumor.
AB  - Mediastinal tumors are heterogeneous and the diagnosis depends on their location
      in the mediastinum. The most frequent tumors are germinal tumor, lymphoma and
      thymoma. The clinical and radiological aspects are often not sufficient to orient
      the diagnosis and biopsy is necessary to confirmed it. Here, we present a rare
      case of an anterior mediastinal mass incidentally detected in a 63 years old man
      during assessment for asthma. The lesion was presumptively diagnosed as a thymic
      epithelial tumor based on location and radiological characteristics. Surgical
      biopsy revealed a primary dedifferentiated mediastinal liposarcoma with multiple
      lung metastases.

PMID- 29449734
TI  - Breast granulomatosis with polyangiitis mimicking breast cancer.
AB  - Inflammatory lesions of the breast encompass primary reactive processes and local
      manifestation of systemic diseases. They are very rare and they are generally
      treated without resort to biopsy. Nevertheless they could be clinically challenge
      mimicking malignant process and needing surgery to reach a correct diagnosis.
      Here we describe a rare case of breast granulomatosis with polyangiitis, which
      presented with radiological and clinical alarming features that immediately
      raised the suspicious of malignancy leading to breast-conserving surgery.

PMID- 29449735
TI  - ALK-positive adenocarcinoma of the lung expressing neuroendocrine markers and
      presenting as a "pituitary adenoma".
AB  - We report an ALK-rearranged adenocarcinoma of the lung presenting as a pituitary
      metastasis, clinically simulating a pituitary adenoma. The patient, a 50 year
      old, former-smoking woman was admitted with a Parinaud's syndrome characterized
      by progressive oculomotor impairment of visual verticality, bitemporal
      hemianopsia and nystagmus. Imaging studies showed a sellar tumor and the biopsy
      revealed a TTF-1 and napsin positive lung adenocarcinoma strongly expressing
      synaptophysin and CD56, also harboring ALK rearrangement. A subsequent CT scan
      disclosed the primary lung mass of the left upper lobe. The patient progressed
      after 4 cycles of cisplatin/pemetrexed as first line treatment, but showed a
      partial response and a significant clinical benefit from the combination of
      ceritinib and nivolumab in a phase Ib trial. Despite its central nervous system
      tropism, ALK-rearranged adenocarcinoma manifesting with pituitary gland
      involvement was never reported. Second generation ALK inhibitors seem the best
      therapeutic strategy.

PMID- 29449736
TI  - Adenoid cystic carcinoma: a rare breast carcinoma.
AB  - Adenoid cystic carcinoma is a rare neoplasm accounting for <0.1% of breast
      carcinomas. The mean age of presentation is fifth to sixth decade of life and it
      generally presents as a painful breast lump. The histological features are
      characteristic with cribriform and acinar pattern of basaloid cells. It is triple
      negative tumor with CD117 and p63 positivity and excellent prognosis.

PMID- 29449737
TI  - Unexpected cause for duodenal obstruction: Brunner's gland hyperplasia.
AB  - Brunner's gland hyperplasia is a rare benign lesion arising from the duodenum. It
      is often an incidental finding on endoscopy with the majority of patients being
      asymptomatic. It may also present with various symptoms depending on location and
      tumor size, such as gastrointestinal bleeding, obstruction and abdominal pain. We
      report an unusual case of large Brunner's gland hyperplasia in 72-years old man,
      admitted to hospital for epigastric pain, recurrent vomiting and significantly
      weight loss. Upper endoscopy showed an obstructive submucosis tumour of the bulb.
      Abdominal computed tomography scan revealed a circumferential thickening and
      stenosing mass of the first part of the duodenum leading to severe obstruction.
      Though pre-operative biopsies were negative, imaging studies and endoscopy were
      strongly suggestive of malignancy and the patient underwent
      duodenocephalopancreatectomy. Brunner's gland hyperplasia may have unusual
      presentation, mimicking malignancy. Therefore, extensive pre-operative
      evaluation, including repetitive tumor biopsies, is necessary to avoid radical
      surgical procedure.

PMID- 29449738
TI  - Parotid gland involvement in Heerfordt syndrome: a case report.
AB  - Sarcoidosis is a multisystemic granulomatous disease characterized by the
      presence of noncaseating granulomas, the exact etiology of which is yet to be
      determined. Most of patients show granulomas located in the lungs or in the
      related lymph nodes. However, lesions can affect any organ. Noncaseating
      granulomas are not a pathognomonic sign of sarcoidosis, being observed also in
      other diseases, therefore the diagnosis is often of exclusion. We report a case
      of sarcoidosis with parotid gland involvement in the context of a Heerfordt
      syndrome, discussing about its clinical presentation, pathogenesis, pathology and
      differential diagnosis with other granulomatous diseases.

PMID- 29449739
TI  - Nasal metastasis as the first manifestation of a metachronous bilateral renal
      cell carcinoma.
AB  - Renal cell carcinoma is one of the most common tumours to spread by extranodal
      metastases to the head and neck. Metastatic renal cell carcinoma to the head and
      neck area has been demonstrated mostly in the paranasal sinuses, parotid gland,
      the mandible, larynx and hypopharinx. Renal cell carcinoma should be excluded
      whenever a metastatic lesion is encountered in the head and neck area, even if
      the metastatic lesion is the first clinical presentation. The diagnosis of
      metastatic RCC should be suspected in any patient with even a remote history of
      renal cell carcinoma. We report a case of 79 year old woman with recurrent
      episodes of rhinorrhea, headache, hyposmia and monolateral right epistaxis, with
      a history of RCC. We describe RCC nasal metastases in a metachronous bilateral
      neoplasm, in which a second occult lesion debuted with a homolateral nasal
      metastases, ten years after left nephrectomy.

PMID- 29449740
TI  - Does V600E BRAF mutation predict vinorelbine efficacy? A proof-of-concept from a
      lung micropapillary adenocarcinoma metastatic to the breast.
AB  - BRAF mutations occur in about 3% of all lung adenocarcinomas and V600E missense
      mutation characterizes about half of BRAF-mutated lung adenocarcinomas and is
      significantly associated with micropapillary pattern and shorter disease-free and
      overall survival rates. In this report, we report a challenging case of a patient
      with a metastatic micropapillary adenocarcinoma of the lung harbouring V600E BRAF
      mutation who experienced a surprising protracted clinical response to metronomic
      vinorelbine. The possible association between the V600E BRAF mutation pathway and
      the effective use of vinca alkaloid is discussed.

PMID- 29449741
TI  - Far Ultraviolet Spectroscopy of Old Novae I. V603 Aquila.
AB  - We present the results of a synthetic spectral analysis of the far ultraviolet
      archival IUE, HST and FUSE observations of the fast old nova V603 Aql, obtained
      some 90 years after its 1918 nova outburst. Our analysis utilizes the new Hubble
      FGS parallax distance for this nearly face-on old nova, a high white dwarf mass
      and a low reddening. Our analysis includes non-truncated optically thick
      accretion disks since V603 Aql is neither a polar nor an intermediate polar. Our
      synthetic spectral modeling of the FUSE and HST spectra analyzed separately
      indicate a mass transfer rate [Formula: see text] for the FUSE and HST spectra
      respectively, assuming a WD mass of 1.2M?. The mass accretion rate also depends
      on the assumed WD mass, and increases by a factor of two for a WD mass of 0.8M?.
      Combining the FUSE and HST spectra together lead to the same results. Potential
      implications are discussed.

PMID- 29449742
TI  - Isolation, Separation, and Preconcentration of Biologically Active Compounds from
      Plant Matrices by Extraction Techniques.
AB  - Development of efficient methods for isolation and separation of biologically
      active compounds remains an important challenge for researchers. Designing
      systems such as organomineral composite materials that allow extraction of a wide
      range of biologically active compounds, acting as broad-utility solid-phase
      extraction agents, remains an important and necessary task. Selective sorbents
      can be easily used for highly selective and reliable extraction of specific
      components present in complex matrices. Herein, state-of-the-art approaches for
      selective isolation, preconcentration, and separation of biologically active
      compounds from a range of matrices are discussed. Primary focus is given to novel
      extraction methods for some biologically active compounds including cyclic
      polyols, flavonoids, and oligosaccharides from plants. In addition, application
      of silica-, carbon-, and polymer-based solid-phase extraction adsorbents and
      membrane extraction for selective separation of these compounds is discussed.
      Potential separation process interactions are recommended; their understanding is
      of utmost importance for the creation of optimal conditions to extract
      biologically active compounds including those with estrogenic properties.

PMID- 29449743
TI  - Caregiver's Burden, Coping, and Psycho-Education in Indian Households with Single
      and Multiple-Affected Members with Schizophrenia.
AB  - There is considerable evidence that family psycho-education combined with
      pharmacological intervention for patients with schizophrenia increases family
      understanding of the illness, reduces the familial burden of care, and improves
      patient outcomes. However, no studies have determined whether the burden of care
      is greater for those families with more than one ill member (multiplex) than for
      families with a single-affected individual (simplex), and whether psycho
      educational programs should be adapted to meet the specific needs of multiplex
      families. This study was conducted at a tertiary care postgraduate teaching
      hospital in New Delhi, India. Caregivers in simplex [n = 50] and multiplex
      families [n = 30] were compared with regard to levels of burden, coping, and the
      impact of psycho-education on family functioning. All the caregiver participants
      attended eight bimonthly, psycho-educational intervention sessions. They were
      assessed on the Burden Assessment Schedule (BAS) and the Coping Check List (CCL)
      before and after psycho-education. Caregivers from the multiplex families
      reported significantly more burden on two domains of the BAS, but there were no
      significant differences between the groups with regard to coping on the CCL.
      Following psycho-education, significant improvement occurred in the majority of
      domains of the BAS and the CCL; the effect sizes varied by domain and family
      type. Multiplex families face a greater burden of care compared with simplex
      families. Currently, available psycho-education programs are moderately effective
      for such families.

PMID- 29449744
TI  - Laurdan and Di-4-ANEPPDHQ probe different properties of the membrane.
AB  - Lipid packing is a crucial feature of cellular membranes. Quantitative analysis
      of membrane lipid packing can be achieved using polarity sensitive probes whose
      emission spectrum depends on the lipid packing. However, detailed insights into
      the exact mechanisms that cause the changes in the spectra are necessary to
      interpret experimental fluorescence emission data correctly. Here, we analysed
      frequently used polarity sensitive probes, Laurdan and di-4-ANEPPDHQ, to test
      whether the underlying physical mechanisms of their spectral changes are the same
      and, thus, whether they report on the same physico-chemical properties of the
      cell membrane. Steady-state spectra as well as time-resolved emission spectra of
      the probes in solvents and model membranes revealed that they probe different
      properties of the lipid membrane. Our findings are important for the application
      of these dyes in cell biology.

PMID- 29449745
TI  - The Drawbacks of Project Funding for Epistemic Innovation: Comparing
      Institutional Affordances and Constraints of Different Types of Research Funding.
AB  - Over the past decades, science funding shows a shift from recurrent block funding
      towards project funding mechanisms. However, our knowledge of how project funding
      arrangements influence the organizational and epistemic properties of research is
      limited. To study this relation, a bridge between science policy studies and
      science studies is necessary. Recent studies have analyzed the relation between
      the affordances and constraints of project grants and the epistemic properties of
      research. However, the potentially very different affordances and constraints of
      funding arrangements such as awards, prizes and fellowships, have not yet been
      taken into account. Drawing on eight case studies of funding arrangements in high
      performing Dutch research groups, this study compares the institutional
      affordances and constraints of prizes with those of project grants and their
      effects on organizational and epistemic properties of research. We argue that the
      prize case studies diverge from project-funded research in three ways: 1) a more
      flexible use, and adaptation of use, of funds during the research process
      compared to project grants; 2) investments in the larger organization which have
      effects beyond the research project itself; and 3), closely related, greater
      deviation from epistemic and organizational standards. The increasing dominance
      of project funding arrangements in Western science systems is therefore argued to
      be problematic in light of epistemic and organizational innovation. Funding
      arrangements that offer funding without scholars having to submit a project
      proposal remain crucial to support researchers and research groups to deviate
      from epistemic and organizational standards.

PMID- 29449746
TI  - High-Quality Carbohydrates and Physical Performance: Expert Panel Report.
AB  - While all experts agreed that protein needs for performance are likely greater
      than believed in past generations, particularly for strength training athletes,
      and that dietary fat could sustain an active person through lower-intensity
      training bouts, current research still points to carbohydrate as an indispensable
      energy source for high-intensity performance.

PMID- 29449747
TI  - CONTINUOUS CALIBRATION IMPROVEMENT: LANDSAT 5 THROUGH LANDSAT 8.
AB  - Launched in February 2013, the Operational Land Imager (OLI) on-board Landsat 8
      continues to perform exceedingly well and provides high science quality data
      globally. Several design enhancements have been made in the OLI instrument
      relative to prior Landsat instruments: pushbroom imaging which provides
      substantially improved Signal-to-Noise Ratio (SNR), spectral bandpasses
      refinement to avoid atmospheric absorption features, 12 bit data resolution to
      provide a larger dynamic range that limits the saturation level, a set of well
      designed onboard calibrators to monitor the stability of the sensor. Some of
      these changes such as refinements in spectral bandpasses compared to earlier
      Landsats and well-designed on-board calibrator have a direct impact on the
      improved radiometric calibration performance of the instrument from both the
      stability of the response and the ability to track the changes. The on-board
      calibrator lamps and diffusers indicate that the instrument drift is generally
      less than 0.1% per year across the bands. The refined bandpasses of the OLI
      indicate that temporal uncertainty of better than 0.5% is possible when the
      instrument is trended over vicarious targets such as Pseudo Invariant Calibration
      Sites (PICS), a level of precision that was never achieved with the earlier
      Landsat instruments. The stability measurements indicated by on-board calibrators
      and PICS agree much better compared to the earlier Landsats, which is very
      encouraging and bodes well for the future Landsat missions too.

PMID- 29449748
TI  - Visualizing the context of citations referencing papers published by Eugene
      Garfield: a new type of keyword co-occurrence analysis.
AB  - During Eugene Garfield's (EG's) lengthy career as information scientist, he
      published about 1500 papers. In this study, we use the impressive oeuvre of EG to
      introduce a new type of bibliometric networks: keyword co-occurrences networks
      based on the context of citations, which are referenced in a certain paper set
      (here: the papers published by EG). The citation context is defined by the words
      which are located around a specific citation. We retrieved the citation context
      from Microsoft Academic. To interpret and compare the results of the new network
      type, we generated two further networks: co-occurrence networks which are based
      on title and abstract keywords from (1) EG's papers and (2) the papers citing
      EG's publications. The comparison of the three networks suggests that papers of
      EG and citation contexts of papers citing EG are semantically more closely
      related to each other than to titles and abstracts of papers citing EG. This
      result accords with the use of citations in research evaluation that is based on
      the premise that citations reflect the cognitive influence of the cited on the
      citing publication.

PMID- 29449750
TI  - Are you in top 1% (10/00)?
AB  - A new simple bibliometric indicator is based on the number of highly cited papers
      (as defined by WoS(r)). It can be used to assess individuals, journals and
      universities. Unlike most other citation-based-indicators it equalizes the
      chances of young scientists (vs. their more experienced colleagues) and of
      scientists working in less-popular disciplines. The ranking of scientists based
      on the new indicator is not correlated with the rankings based upon the number of
      citations or on the Hirsch-index.

PMID- 29449749
TI  - Reference publication year spectroscopy (RPYS) of Eugene Garfield's publications.
AB  - Which studies, theories, and ideas have influenced Eugene Garfield's scientific
      work? Recently, the method reference publication year spectroscopy (RPYS) has
      been introduced, which can be used to answer this and related questions. Since
      then, several studies have been published dealing with the historical roots of
      research fields and scientists. The program CRExplorer
      (http://www.crexplorer.net) was specifically developed for RPYS. In this study,
      we use this program to investigate the historical roots of Eugene Garfield's
      oeuvre.

PMID- 29449751
TI  - Betweenness and diversity in journal citation networks as measures of
      interdisciplinarity-A tribute to Eugene Garfield.
AB  - Journals were central to Eugene Garfield's research interests. Among other
      things, journals are considered as units of analysis for bibliographic databases
      such as the Web of Science and Scopus. In addition to providing a basis for
      disciplinary classifications of journals, journal citation patterns span networks
      across boundaries to variable extents. Using betweenness centrality (BC) and
      diversity, we elaborate on the question of how to distinguish and rank journals
      in terms of interdisciplinarity. Interdisciplinarity, however, is difficult to
      operationalize in the absence of an operational definition of disciplines; the
      diversity of a unit of analysis is sample-dependent. BC can be considered as a
      measure of multi-disciplinarity. Diversity of co-citation in a citing document
      has been considered as an indicator of knowledge integration, but an author can
      also generate trans-disciplinary-that is, non-disciplined-variation by citing
      sources from other disciplines. Diversity in the bibliographic coupling among
      citing documents can analogously be considered as diffusion  or differentiation
      of knowledge across disciplines. Because the citation networks in the cited
      direction reflect both structure and variation, diversity in this direction is
      perhaps the best available measure of interdisciplinarity at the journal level.
      Furthermore, diversity is based on a summation and can therefore be decomposed;
      differences among (sub)sets can be tested for statistical significance. In the
      appendix, a general-purpose routine for measuring diversity in networks is
      provided.

PMID- 29449752
TI  - Capturing 'R&D excellence': indicators, international statistics, and innovative
      universities.
AB  - Excellent research may contribute to successful science-based technological
      innovation. We define 'R&D excellence' in terms of scientific research that has
      contributed to the development of influential technologies, where 'excellence'
      refers to the top segment of a statistical distribution based on internationally
      comparative performance scores. Our measurements are derived from frequency
      counts of literature references ('citations') from patents to research
      publications during the last 15 years. The 'D' part in R&D is represented by the
      top 10% most highly cited 'excellent' patents worldwide. The 'R' part is captured
      by research articles in international scholarly journals that are cited by these
      patented technologies. After analyzing millions of citing patents and cited
      research publications, we find very large differences between countries worldwide
      in terms of the volume of domestic science contributing to those patented
      technologies. Where the USA produces the largest numbers of cited research
      publications (partly because of database biases), Switzerland and Israel
      outperform the US after correcting for the size of their national science
      systems. To tease out possible explanatory factors, which may significantly
      affect or determine these performance differentials, we first studied high-income
      nations and advanced economies. Here we find that the size of R&D expenditure
      correlates with the sheer size of cited publications, as does the degree of
      university research cooperation with domestic firms. When broadening our
      comparative framework to 70 countries (including many medium-income nations)
      while correcting for size of national science systems, the important explanatory
      factors become the availability of human resources and quality of science
      systems. Focusing on the latter factor, our in-depth analysis of 716 research
      intensive universities worldwide reveals several universities with very high
      scores on our two R&D excellence indicators. Confirming the above macro-level
      findings, an in-depth study of 27 leading US universities identifies research
      expenditure size as a prime determinant. Our analytical model and quantitative
      indicators provides a supplementary perspective to input-oriented statistics
      based on R&D expenditures. The country-level findings are indicative of
      significant disparities between national R&D systems. Comparing the performance
      of individual universities, we observe large differences within national science
      systems. The top ranking 'innovative' research universities contribute
      significantly to the development of advanced science-based technologies.

PMID- 29449753
TI  - Do younger Sleeping Beauties prefer a technological prince?
AB  - In this paper we investigate recent Sleeping Beauties cited in patents (SB
      SNPRs). We find that the increasing trend of the relative number of SBs stopped
      around 1998. Moreover, we find that the time lag between the publication year of
      the SB-SNPRs and their first citation in a patent is becoming shorter in recent
      years. Our observations also suggest that, on average, in the more recent years
      SBs are awakened increasingly earlier by a 'technological prince' rather than by
      a 'scientific prince'. These observations suggest that SBs with technological
      importance are 'discovered' earlier in an application-oriented context. Then,
      because of this earlier recognized technological relevance, papers may be cited
      also earlier in a scientific context. Thus early recognized technological
      relevance may 'prevent' papers to become an SB. The scientific impact of Sleeping
      Beauties is generally not necessarily related to the technological importance of
      the SBs, as far as measured with number and impact of the citing patents. The
      analysis of the occurrence of inventor-author relations as well as the citation
      years of inventor-author patents suggest that the scientific awakening of
      Sleeping Beauties only rarely occurs by inventor-author self-citation.

PMID- 29449754
TI  - Behavioural and physiological responses of laying hens to automated monitoring
      equipment.
AB  - Automated monitoring of behaviour can offer a wealth of information in
      circumstances where observing behaviour is difficult or time consuming. However,
      this often requires attaching monitoring devices to the animal which can alter
      behaviour, potentially invalidating any data collected. Birds often show
      increased preening and energy expenditure when wearing devices and, especially in
      laying hens, there is a risk that individuals wearing devices will attract
      aggression from conspecifics. We studied the behavioural and physiological
      response of 20 laying hens to backpacks containing monitoring devices fastened
      with elastic loops around the wing base. We hypothesised that backpacks would
      lead to a stress-induced decrease in peripheral temperature, increased preening,
      more aggression from conspecifics, and reduced bodyweights. This was evaluated by
      thermography of the eye and comb (when isolated after fitting backpacks), direct
      observations of behaviour (when isolated, when placed back into the group, and on
      later days), and weighing (before and after each 7-day experimental period). Each
      hen wore a backpack during one of the two experimental periods only and was used
      as her own control. Contrary to our hypothesis, eye temperature was higher when
      hens wore a backpack (No backpack: 30.2  degrees C (IQR: 29.0-30.6) vs. Backpack:
      30.9  degrees C (IQR: 30.0-32.0), P < 0.001). Eye temperature of hens wearing a
      backpack was strongly correlated to the time spent preening (rs = 0.8, P <
      0.001), suggesting that the higher temperatures may have been due to preening
      itself, or to a low head position or decreased heat dissipation when preening
      under the wings. Aggressive behaviour was very rare and no effect of the
      backpacks was found. In line with our hypothesis, backpacks increased preening on
      the day of fitting, both when isolated (No backpack: 0% (IQR: 0-1) vs. Backpack:
      22% (IQR: 1-43), P < 0.01) and when back in the group (No backpack: 0% (IQR: 0
      27) vs. Backpack: 43% (IQR: 5-77), P < 0.001). However, no effect on preening was
      observed 2-7 days afterwards. Other behavioural changes suggested that on the day
      of fitting hens prioritized attempts to (re)move the backpack and were less
      attentive to their surroundings. However, only equipment pecking (i.e., pecking
      the backpack or leg rings) was still affected 2-7 days after fitting (No
      backpack: 0 pecks/hen/minute (IQR: 0-0), vs. Backpack: 0 (IQR: 0-0.07), P <
      0.05). We found no effect of our backpacks on bodyweight. In conclusion, our
      backpacks seem suitable to attach monitoring equipment to hens with only a very
      minor effect on their behaviour after a short acclimation period (<=2 days).

PMID- 29449755
TI  - Catalytic liquefaction of human feces over Ni-Tm/TiO2 catalyst and the influence
      of operating conditions on products.
AB  - In this study, human feces were hydrothermal liquefied and converted into
      biocrude over Ni-Tm/TiO2 catalyst. The influence of catalysts, reaction
      temperature, and holding time on the distribution of products and element content
      of biocrude was assessed. The biocrude yield increased to 53.16% with a reaction
      temperature of 330  degrees C, a holding time of 30 min, and adding Ni-Tm/TiO2
      catalyst while the liquefaction conversion peaked at 89.61%. The biocrude had an
      HHV of 36.64 MJ/kg and was similar to heavy crude oil. The biocrude is rich in
      fatty acid amides, esters, and oxygen-containing-only heteroatom-ring compounds
      as well as some nitrogen-containing heteroatom-ring compounds. The main gaseous
      products were CO2, CH4, and C2H6. Hydrothermal liquefaction over Ni-Tm/TiO2
      catalyst could be a potential method to handle human excrement treatment and
      produce biofuel.

PMID- 29449756
TI  - Fluorescence lifetime microscopy with a time- and space-resolved single-photon
      counting detector.
AB  - We have recently developed a wide-field photon-counting detector (the H33D
      detector) having high-temporal and high-spatial resolutions and capable of
      recording up to 500,000 photons per sec. Its temporal performance has been
      previously characterized using solutions of fluorescent materials with different
      lifetimes, and its spatial resolution using sub-diffraction objects (beads and
      quantum dots). Here we show its application to fluorescence lifetime imaging of
      live cells and compare its performance to a scanning confocal TCSPC approach.
      With the expected improvements in photocathode sensitivity and increase in
      detector throughput, this technology appears as a promising alternative to the
      current lifetime imaging solutions.

PMID- 29449758
TI  - An assessment of forest biomass maps in Europe using harmonized national
      statistics and inventory plots.
AB  - Maps of aboveground forest biomass based on different input data and modelling
      approaches have been recently produced for Europe, opening up the possibility for
      several applications and products not obtainable by summary statistics. However,
      the accuracy assessment of the existing maps is limited by the lack of reference
      data consistent over the study region and representative of the maps cells. Here,
      we used harmonized forest biomass data for 26 European countries derived by
      National Forest Inventories using a common biomass definition and estimator to
      assess four biomass maps. The assessment was performed at regional, national and
      sub-national scales using harmonized statistics derived from almost half million
      ground plot measurements, and at pixel level using a subset of 22,166 plots
      covering most European forest types. The field plots were temporally aligned with
      the maps using growth rates and further screened using an innovative approach
      based on tree cover variability to remove the plots not representative of the map
      cells. The harmonized reference data showed that all maps tended to overestimate
      at low biomass (<100 Mg ha-1) and underestimate at medium - high biomass (>100 Mg
      ha-1), resulting in an overall negative bias (23-43 Mg ha-1 at national level)
      relative to the harmonized estimates. The maps relative errors ranged from 29% to
      40% at national level and increased at higher resolutions, reaching 58-67% at
      pixel level. We also assessed the effect of the harmonization of the national
      statistics and report that the harmonized biomass values present significant
      differences compared to the national estimates for 14 countries, and provide a
      slightly higher stock (+3.8%) at European scale. We show that harmonized and
      representative reference data are essential to properly assess the accuracy of
      biomass maps, and we further identify the factors affecting the maps performance
      and provide indications for their improvements.

PMID- 29449759
TI  - DE NOVO ASYMMETRIC APPROACH TO THE DISACCHARIDE PORTION OF SCH-47554.
AB  - A method for the asymmetric synthesis of the disaccharide portion of SCH-47554
      has been developed in 6 steps. The route is shorter than the reported route to a
      related disaccharide. The route involves the use of the Noyori reduction to
      establish the asymmetry of the d- and l-sugar portion of the molecule.
      Diastereoselective Pd-glycosylation reaction and subsequent post-glycosylation
      transformation are used to establish the remaining stereocenter.

PMID- 29449760
TI  - Pediatric Psychologists' Career Satisfaction: 2015 Society of Pediatric
      Psychology Workforce Survey Results.
AB  - : Little is known about the career satisfaction of pediatric psychologists, who
      specialize in psychological research, teaching, and clinical service in the
      context of pediatric healthcare. As part of the larger Society of Pediatric
      Psychology Workforce Survey and in collaboration with the American Psychological
      Association Center for Workforce Studies, this study aimed to: (1) describe the
      career domains which pediatric psychologists perceive to be important and their
      satisfaction in each domain, and (2) compare satisfaction of pediatric
      psychologists across work settings, number of positions, appointment duration,
      professional roles, career stage, academic rank, and gender. Responses from 336
      pediatric psychologists demonstrated high career satisfaction. Domains of career
      satisfaction that received mean scores indicating high importance include balance
      of work and personal lives, peer/collegial support, and flexibility and choice in
      the workplace, but on average respondents reported being only somewhat satisfied
      in these domains. Total satisfaction scores were significantly higher among
      pediatric psychologists in 9-10 month appointments, primarily research careers,
      and at higher academic ranks, but scores were similar across employment settings
      and genders. To enhance career satisfaction and retention, pediatric
      psychologists may seek additional mentorship or explore new employment roles, and
      administrators and managers may consider adopting workplace policies or making
      environmental changes that could address specific areas of need. Public
      Significance Statement: This study suggests that overall, pediatric psychologists
      are highly satisfied with their employment. However, there may be some important
      aspects of their work that could be more satisfying. The findings have
      implications for identifying professional development strategies that can
      maintain or enhance satisfaction.

PMID- 29449761
TI  - Active Localization and Tracking of Needle and Target in Robotic Image-Guided
      Intervention Systems.
AB  - This paper describes a framework of algorithms for the active localization and
      tracking of flexible needles and targets during image-guided percutaneous
      interventions. The needle and target configurations are tracked by Bayesian
      filters employing models of the needle and target motions and measurements of the
      current system state obtained from an intra-operative imaging system which is
      controlled by an entropy-minimizing active localization algorithm. Versions of
      the system were built using particle and unscented Kalman filters and their
      performance was measured using both simulations and hardware experiments with
      real magnetic resonance imaging data of needle insertions into gel phantoms.
      Performance of the localization algorithms is given in terms of accuracy of the
      predictions and computational efficiency is discussed.

PMID- 29449757
TI  - Why and how the early-life environment affects development of coping behaviours.
AB  - Understanding the ways in which individuals cope with threats, respond to
      challenges, make use of opportunities and mediate the harmful effects of their
      surroundings is important for predicting their ability to function in a rapidly
      changing world. Perhaps one of the most essential drivers of coping behaviour of
      adults is the environment experienced during their early-life development.
      Although the study of coping, defined as behaviours displayed in response to
      environmental challenges, has a long and rich research history in biology, recent
      literature has repeatedly pointed out that the processes through which coping
      behaviours develop in individuals are still largely unknown. In this review, we
      make a move towards integrating ultimate and proximate lines of coping behaviour
      research. After broadly defining coping behaviours (1), we review why, from an
      evolutionary perspective, the development of coping has become tightly linked to
      the early-life environment (2), which relevant developmental processes are most
      important in creating coping behaviours adjusted to the early-life environment
      (3), which influences have been shown to impact those developmental processes (4)
      and what the adaptive significance of intergenerational transmission of coping
      behaviours is, in the context of behavioural adaptations to a fast changing world
      (5). Important concepts such as effects of parents, habitat, nutrition, social
      group and stress are discussed using examples from empirical studies on mammals,
      fish, birds and other animals. In the discussion, we address important problems
      that arise when studying the development of coping behaviours and suggest
      solutions.

PMID- 29449762
TI  - Fast covariance estimation for sparse functional data.
AB  - Smoothing of noisy sample covariances is an important component in functional
      data analysis. We propose a novel covariance smoothing method based on penalized
      splines and associated software. The proposed method is a bivariate spline
      smoother that is designed for covariance smoothing and can be used for sparse
      functional or longitudinal data. We propose a fast algorithm for covariance
      smoothing using leave-one-subject-out cross-validation. Our simulations show that
      the proposed method compares favorably against several commonly used methods. The
      method is applied to a study of child growth led by one of coauthors and to a
      public dataset of longitudinal CD4 counts.

PMID- 29449763
TI  - The history of IFOMPT: paving the way to global leadership in OMPT excellence.

PMID- 29449764
TI  - The effect of manual therapy and neuroplasticity education on chronic low back
      pain: a randomized clinical trial.
AB  - Objective: To determine if a neuroplasticity educational explanation for a manual
      therapy technique will produce a different outcome compared to a traditional
      mechanical explanation. Methods: Sixty-two patients with chronic low back pain
      (CLBP) were recruited for the study. Following consent, demographic data were
      obtained as well as pain ratings for low back pain (LBP) and leg pain (Numeric
      Pain Rating Scale), disability (Oswestry Disability Index), fear-avoidance (Fear
      Avoidance-Beliefs Questionnaire), forward flexion (fingertips-to-floor), and
      straight leg raise (SLR) (inclinometer). Patients were then randomly allocated to
      receive one of two explanations (neuroplasticity or mechanical), a manual therapy
      technique to their lumbar spine, followed by post-intervention measurements of
      LBP, leg pain, forward flexion, and SLR. Results: Sixty-two patients (female 35
      [56.5%]), with a mean age of 60.1 years and mean duration of 9.26 years of CLBP
      participated in the study. There were no statistically significant interactions
      for LBP (p = .325), leg pain (p = .172), and trunk flexion (p = .818) between the
      groups, but SLR showed a significant difference in favor of the neuroplasticity
      explanation (p = .041). Additionally, the neuroplasticity group were 7.2 times
      (95% confidence interval = 1.8-28.6) more likely to improve beyond the MDC on the
      SLR than participants in the mechanical group. Discussion: The results of this
      study show that a neuroplasticity explanation, compared to a traditional
      biomechanical explanation, resulted in a measureable difference in SLR in
      patients with CLBP when receiving manual therapy. Future studies need to explore
      if the increase in SLR correlated to changes in cortical maps of the low back.

PMID- 29449765
TI  - Application of the McKenzie system of Mechanical Diagnosis and Therapy (MDT) in
      patients with shoulder pain; a prospective longitudinal study.
AB  - Objectives: The primary objective was to determine if the pain and function
      response to the McKenzie system of Mechanical Diagnosis and Therapy (MDT) differs
      by MDT classification category at two and four weeks following the start of MDT
      treatment for shoulder complaints. The secondary objective was to describe the
      frequency of discharge over time by MDT classification. Methods: International,
      MDT-trained study collaborators recruited 93 patients attending physiotherapy for
      rehabilitation of a shoulder problem. The Numeric Pain Rating Scale (NPRS) and
      the Upper Extremity Functional Index (UEFI) were collected at the initial
      assessment and two and four weeks after treatment commenced. A two-way mixed
      model analysis of variance with planned pairwise comparisons was performed to
      identify where the differences between MDT classification groups actually
      existed. Results: The Derangement and Spinal classifications had significantly
      lower NPRS scores than the Dysfunction group at week 2 and week 4 (p < 0.05). The
      Derangement and Spinal classifications had significantly higher UEFI scores than
      the Dysfunction group at week 2 and week 4 (p < 0.05). The frequency of discharge
      at week 2 was 37% for both Derangement and Spinal classifications, with no
      discharges for the Dysfunction classification at this time point. The frequency
      of discharge at week 4 was 83, 82 and 15% for the Derangement, Spinal and
      Dysfunction classifications, respectively. Discussion: Classifying patients with
      shoulder pain using the MDT system can impact treatment outcomes and the
      frequency of discharge. When MDT-trained clinicians are allowed to match the
      intervention to a specific MDT classification, the outcome is aligned with the
      response expectation of the classification.Level of Evidence: 2b.

PMID- 29449766
TI  - Directional preference of the wrist: a preliminary investigation.
AB  - Background: Directional preference is a phenomenon that occurs in musculoskeletal
      disorders. It is associated with improved symptomatic and functional outcomes.
      Research has shown a 90% increase in the identification of directional preference
      in the peripheral joints between 2006 and 2012. There is currently no research
      analyzing if predictive variables exist for establishing directional preference.
      Case Description: This report presents 19 consecutive patients with wrist pain.
      These patients were evaluated using a mechanical diagnosis and therapy (MDT)
      based assessment. Patients were classified into the mechanical syndromes
      Derangement, Dysfunction, Postural, and Other. Patients classified with wrist
      Derangement were assessed for the presence of directional preference. Secondary
      analysis of predetermined variables was performed for association with
      directional preference. One case description was included to demonstrate MDT
      assessment, treatment, and clinical reasoning. Results: Of the 19 patients
      evaluated, 15 (79%) were classified as having wrist Derangement. All patients
      with wrist Derangement demonstrated directional preference. Eight movements were
      found to establish directional preference. Each was unique with varying degrees
      of direction, load, and force. Discussion: This report found directional
      preference to be higher (79%) than previously reported values. Historical and
      physical examination findings were analyzed to determine if there were associated
      variables of directional preference. Excessive mechanical stress was found to be
      the most associated factor in predicting directional preference. These findings
      may lead to a greater understanding of peripheral MDT assessment, which may lead
      to increased identification of directional preference and improved patient
      outcomes. Level of Evidence: 4.

PMID- 29449767
TI  - Novel treatment of lateral ankle sprains using the Mulligan concept: an
      exploratory case series analysis.
AB  - Objective: The purpose of this study was to examine the effect of the Mulligan
      Concept (MC) Mobilization with movement (MWM) in the treatment of clinically
      diagnosed acute lateral ankle sprains in competitive athletes. Methods: A
      prospective case series of 5 adolescent patients, ages ranging from 14 to 18
      years (mean = 15.8 +/- 1.64), that suffered an acute lateral ankle sprain (LAS).
      Patients were treated with the MC lateral ankle MWM. Mobilization was directed at
      the distal fibula or, using a modified MWM, 2-3 inches proximal to the distal
      fibula. Using paired t-tests and descriptive statistics (mean and standard
      deviation) results were analyzed. Results: Treatment lasted an average of 9 days
      (mean = 9.2, +/-SD 3.96) from intake to discharge. During that time frame,
      patients reported decreases in pain on the numeric pain rating scale (NRS),
      disability on the Disablement in the Physically Active (DPA) scale and an
      increase in function on the patient-specific functional scale (PSFS); and an
      immediate decrease in pain on the NRS within the first treatment. The minimal
      detectable change for the PSFS and NRS were exceeded from intake to discharge.
      Additionally, the minimally clinical important differences were exceeded on the
      NRS and DPA scale. Discussion: The evidence presented in this Level-4 case series
      supports the use of the MC lateral ankle MWM to treat patients diagnosed with
      acute grade II LAS. Patients in this case series reported immediate decreases in
      pain and immediate increases in function. Therefore, further investigation of the
      MC lateral ankle MWM is warranted.

PMID- 29449768
TI  - Grade-IV inferior glenohumeral mobilization does not immediately alter shoulder
      and scapular muscle activity: a repeated-measures study in asymptomatic
      individuals.
AB  - Objectives: To assess: (1) the presence of any carry-over effect between
      interventions; (2) the immediate effects of inferior shoulder mobilization on
      shoulder and scapular muscle activity; and (3) to compare muscle activity
      response between the control and mobilization conditions. Repeated measures,
      cross-over, pre-post intervention study with sample of convenience. Methods:
      Twenty-two asymptomatic individuals performed 10 repetitions of shoulder
      abduction before and after the control and mobilization, with a dosage of three
      sets of 30-s duration, with grade-IV. The order of intervention was randomized.
      Surface electromyography was used for recording activity of upper and lower
      trapezius; anterior, middle and posterior deltoids; supraspinatus; infraspinatus;
      and serratus anterior. Repeated measures mixed-model analysis of variance was
      used to assess immediate changes in muscle activity levels following inferior
      shoulder mobilization. Statistical parametric mapping (SPM) was used for
      comparing muscle activity waveforms between control and mobilization conditions
      throughout the range of motion. Results: No systematic changes in muscle activity
      levels were found between: (1) baseline and follow-up for each condition, at the
      concentric and eccentric phases of shoulder abduction; (2) control and
      mobilization conditions during the concentric and eccentric phases of shoulder
      abduction. SPM results suggested no differences in muscle activity pattern
      between conditions. Conclusions: Inferior shoulder mobilization did not produce
      immediate effects on shoulder and scapular muscle activity. It is possible that
      the dose used was insufficient to generate an immediate neuromuscular response to
      the mobilization.

PMID- 29449769
TI  - Translational manipulation under anesthesia for patients with frozen shoulder: a
      case series study with five-year health care utilization and post-manipulative
      arthroscopic findings.
AB  - Study Design: Case series study. Objectives: Although there have been no reported
      complications from translational manipulation under anesthesia (tMUA) for
      individuals with adhesive capsulitis (AC) there are no cases reporting surgical
      findings post tMUA. Also, there are no studies evaluating health care utilization
      following tMUA. The purpose of this study was to: (1) report clinical outcomes
      following tMUA, (2) describe relevant health care costs and utilization following
      tMUA, and (3) summarize findings from two cases receiving joint arthroscopy
      following tMUA. Methods: Fourteen Individuals with AC underwent tMUA. Range of
      motion (ROM) and Shoulder Pain and Disability Index (SPADI) values were collected
      at baseline and six weeks follow-up. Shoulder-related health care cost and
      utilization were analyzed for a five-year period following tMUA. Two additional
      patients with AC underwent tMUA followed by arthroscopic assessment for evidence
      of iatrogenic injury. Results: Thirteen patients completed the six-week follow
      up. Mean change scores for ROM and SPADI values were flexion; +38.5 degrees ,
      abduction; +71.1 degrees , external rotation (shoulder abducted); +49.8 degrees ,
      internal rotation (shoulder abducted); +26.6 degrees , SPADI scores; +44.4. 13
      patient records were analyzed for health care utilization. Ten of the 13 patients
      utilized no additional shoulder-related health care. Surgical evaluation revealed
      no evidence of iatrogenic injury. Discussion: Clinical outcomes were similar to
      previous studies. Utilization data indicated that for the majority of patients,
      little shoulder-related health care was utilized. Surgical evaluation provided
      further evidence that tMUA performed by a physical therapist is safe. Future
      research will be required to establish a causal relationship between tMUA and the
      results observed in this study. Level of Evidence: Therapy, Level 4.

PMID- 29449770
TI  - Adverse events following cervical manipulative therapy: consensus on
      classification among Dutch medical specialists, manual therapists, and patients.
AB  - Objectives: To obtain consensus-based agreement on a classification system of
      adverse events (AE) following cervical spinal manipulation. The classification
      system should be comprised of clear definitions, include patients' and
      clinicians' perspectives, and have an acceptable number of categories. Methods:
      Design: A three-round Delphi study. Participants: Thirty Dutch participants
      (medical specialists, manual therapists, and patients) participated in an online
      survey. Procedure: Participants inventoried AE and were asked about their
      preferences for either a three- or a four-category classification system. The
      identified AE were classified by two analysts following the International
      Classification of Functioning, Disability and Health (ICF), and the International
      Classification of Diseases and Related Health Problems (ICD-10). Participants
      were asked to classify the severity for all AE in relation to the time duration.
      Results: Consensus occurred in a three-category classification system. There was
      strong consensus for 16 AE in all severities (no, minor, and major AE) and all
      three time durations [hours, days, weeks]. The 16 AE included anxiety, flushing,
      skin rash, fainting, dizziness, coma, altered sensation, muscle tenderness, pain,
      increased pain during movement, radiating pain, dislocation, fracture, transient
      ischemic attack, stroke, and death. Mild to strong consensus was reached for 13
      AE. Discussion: A consensus-based classification system of AE is established
      which includes patients' and clinicians' perspectives and has three categories.
      The classification comprises a precise description of potential AE in accordance
      with internationally accepted classifications. After international validation,
      clinicians and researchers may use this AE classification system to report AE in
      clinical practice and research.

PMID- 29449771
TI  - The effectiveness of manual physical therapy interventions in pediatric patients
      with anterior hip pain: a retrospective study.
AB  - Objectives: The purposes of this study were to: (1) assess the benefit of adding
      manual therapy (MT) to physical therapy care in pediatric patients with anterior
      hip pain; (2) assess the relative risk of adverse reactions when MT is used; and
      (3) report the types of MT used. Methods: This study was a retrospective chart
      review of patients treated in a hospital-based sports medicine clinic. The charts
      of 201 patients (mean age = 14.23 +/- 2.15 years) met the inclusion criteria and
      were reviewed. Patients were grouped into those who received MT during their
      episode of care, and those who did not. Pain efficiency (change in pain/number of
      visits), number and type of adverse reactions, as well as frequency and type of
      manual therapy interventions used, were the outcomes of interest. Results: The
      mean pain efficiency was significantly less if manual therapy was performed (MT =
      0.60 [95% CI 0.47-0.72], no MT = 0.80 [95% CI 0.71-0.90] p = 0.01). There was no
      significant difference between groups in risk of adverse reactions (MT = 5, no MT
      = 5). The number of visits was significantly different between groups (MT = 9.43
      +/- 3.9 sessions, and no MT = 7.6 +/- 5.2 sessions). Discussion: MT did not
      increase the risk of an adverse reaction in pediatric patients with anterior hip
      pain. While it appears to be a safe intervention, it did not improve pain
      efficiency or patient adherence. Future research should be performed to assess
      the effectiveness of MT, when performed by skilled therapists, in pediatric
      patients with hip pain in a controlled manner.Level of Evidence: 3b.

PMID- 29449772
TI  - Differential examination, diagnosis and management for tingling in toes: fellow's
      case problem.
AB  - Background: The diagnosis of chronic exertional compartment syndrome can be
      challenging as other pathologies involving bone, muscle, nerve and vascular
      structures can mimic the syndrome. The purpose of this Fellow's Case Problem is
      to describe the clinical decision-making and physical therapy differential
      diagnosis regarding a 25-year-old patient with un-resolved neurovascular
      complaints following chronic exertional compartment syndrome surgical release.
      Diagnosis: After surgery, the patient's previous complaint of numbness and
      tingling in the plantar surfaces of her first and second toes of right foot was
      still present. The patient's concordant symptoms in toes were reproduced
      proximally in the lumbar spine and distally in the tarsal tunnel. Discussion: The
      lumbar spine can refer symptoms to the lower extremities and needs to be ruled
      out as the source of the patient's complaint whenever neurovascular symptoms such
      as numbness and tingling are present. The discovery of the relationship of the
      lumbar spine with the tingling in the toes addressed one of the patient's primary
      concerns that was not resolved from the surgery. Level of Evidence: 4.

PMID- 29449773
TI  - Potential Breast Anticancer Drug Targets Revealed by Differential Gene Regulatory
      Network Analysis and Molecular Docking: Neoadjuvant Docetaxel Drug as a Case
      Study.
AB  - Understanding gene-gene interaction and its causal relationship to protein
      protein interaction is a viable route for understanding drug action at the
      genetic level, which is largely hindered by inability to robustly map gene
      regulatory networks. Here, we use biological prior knowledge of family-to-family
      gene interactions available in the KEGG database to reveal individual gene-to
      gene interaction networks that underlie the gene expression profiles of 2 cell
      line data sets, sensitive and resistive to neoadjuvant docetaxel breast
      anticancer drug. Comparison of the topology of the 2 networks revealed that the
      resistant network is highly connected with 2 large domains of connectivity: one
      in which the RAF1 and MAP2K2 genes form hubs of connectivity and another in which
      the RAS gene is highly connected. On the contrary, the sensitive network is
      highly disrupted with a lower degree of connectivity. We investigated the
      interactions of the neoadjuvant docetaxel drug with the protein chains encoded by
      gene-gene interactions that underlie the disruption of the sensitive network
      topology using protein-protein and drug-protein docking techniques. We found that
      the sensitive network is likely to be disrupted by interaction of the neoadjuvant
      docetaxel drug with the DAXX and FGR1 proteins, which is consistent with the
      observed accumulation of cytoplasmic DAXX and overexpression of FGR1 precursors
      in cancer cell lines. This indicates that the DAXX and FGR1 proteins could be
      potential targets for the neoadjuvant docetaxel drug. The work, therefore,
      provides a new route for understanding the effect of the drug mode of action from
      the viewpoint of the change in the topology of gene-gene regulatory networks and
      provides a new avenue for bridging the gap between gene-gene interactions and
      protein-protein interactions which could have deep implications on mainstream
      drug development protocols.

PMID- 29449774
TI  - Reactive Oxygen Species: A Key Constituent in Cancer Survival.
AB  - Background: Cancer is one of the major heterogeneous disease with high morbidity
      and mortality with poor prognosis. Elevated levels of reactive oxygen species
      (ROS), alteration in redox balance, and deregulated redox signaling are common
      hallmarks of cancer progression and resistance to treatment. Mitochondria
      contribute mainly in the generation of ROS during oxidative phosphorylation.
      Elevated levels of ROS have been detected in cancers cells due to high metabolic
      activity, cellular signaling, peroxisomal activity, mitochondrial dysfunction,
      activation of oncogene, and increased enzymatic activity of oxidases,
      cyclooxygenases, lipoxygenases, and thymidine phosphorylases. Cells maintain
      intracellular homeostasis by developing an immense antioxidant system including
      catalase, superoxide dismutase, and glutathione peroxidase. Besides these enzymes
      exist an important antioxidant glutathione and transcription factor Nrf2 which
      contribute in balancing oxidative stress. Reactive oxygen species-mediated
      signaling pathways activate pro-oncogenic signaling which eases in cancer
      progression, angiogenesis, and survival. Concomitantly, to maintain ROS
      homeostasis and evade cancer cell death, an increased level of antioxidant
      capacity is associated with cancer cells. Conclusions: This review focuses the
      role of ROS in cancer survival pathways and importance of targeting the ROS
      signal involved in cancer development, which is a new strategy in cancer
      treatment.

PMID- 29449775
TI  - Prion Proteins Without the Glycophosphatidylinositol Anchor: Potential Biomarkers
      in Neurodegenerative Diseases.
AB  - Prion protein (PrP) is a biomolecule that is involved in neuronal signaling,
      myelinization, and the development of neurodegenerative diseases. In the cell,
      PrP is shed by the ADAM10 protease. This process generates PrP molecules that
      lack glycophosphatidylinositol anchor, and these molecules incorporate into toxic
      aggregates and neutralize toxic oligomers. Due to this dual role, these molecules
      are important biomarkers for neurodegenerative diseases. In this review, we
      present shed PrP as a potential biomarker, with a focus on PrP226*, which may be
      the main biomarker for predicting neurodegenerative diseases in humans.

PMID- 29449777
TI  - A Homogeneous Time-Resolved Fluorescence Immunoassay Method for the Measurement
      of Compound W.
AB  - Objective: Using compound W (a 3,3'-diiodothyronine sulfate [T2S] immuno
      crossreactive material)-specific polyclonal antibodies and homogeneous time
      resolved fluorescence immunoassay assay techniques (AlphaLISA) to establish an
      indirect competitive compound W (ICW) quantitative detection method. Method:
      Photosensitive particles (donor beads) coated with compound W or T2S and rabbit
      anti-W antibody were incubated with biotinylated goat anti-rabbit antibody. This
      constitutes a detection system with streptavidin-coated acceptor particle. We
      have optimized the test conditions and evaluated the detection performance.
      Results: The sensitivity of the method was 5 pg/mL, and the detection range was 5
      to 10 000 pg/mL. The intra-assay coefficient of variation averages <10% with
      stable reproducibility. Conclusions: The ICW-AlphaLISA shows good stability and
      high sensitivity and can measure a wide range of compound W levels in extracts of
      maternal serum samples. This may have clinical application to screen congenital
      hypothyroidism in utero.

PMID- 29449776
TI  - Nkx2-3-A Slippery Slope From Development Through Inflammation Toward
      Hematopoietic Malignancies.
AB  - The development of peripheral lymphoid tissues from the mesoderm is the result of
      a complex convergence combining lymphohematopoietic differentiation with the
      local specification of nonhematopoietic mesenchymal components. Although the
      various transcriptional regulators with fate-determining effects in diversifying
      the mobile leukocyte subsets have been thoroughly studied and identified, the
      tissue-specific determinants promoting the regional differentiation of resident
      mesenchyme are less understood. Of these factors, various members of the NK-class
      Nkx paralogues have emerged as key regulators for the organogenesis of spleen and
      mucosal lymphoid tissues, and recent data have also indicated their involvement
      in various pathological events, including gut inflammation and hematopoietic
      malignancies. Here, we summarize available data on the roles of Nkx2-3 in
      lymphoid tissue development and discuss its possible value as a developmental
      marker and disease-associated pathogenic trait.

PMID- 29449778
TI  - Why Do Those With Long-Term Substance Use Disorders Stop Abusing Substances? A
      Qualitative Study.
AB  - Although a significant proportion of adults recover from substance use disorders
      (SUDs), little is known about how they reach this turning point or why they stop
      using. The purpose of the study was to explore the factors that influence
      reasoning and decision making about quitting substance use after a long-term SUD.
      Semistructured interviews were conducted with 18 participants, each of whom had
      been diagnosed with a SUD and had been abstinent for at least 5 years. A resource
      group of peer consultants in long-term recovery from SUDs contributed to the
      study's planning, preparation, and initial analyses. Participants recalled
      harmful consequences and significant events during their years of substance use.
      Pressure and concern from close family members were important in their initial
      efforts to abstain from substance use. Being able to imagine a different life,
      and the awareness of existing treatment options, promoted hope and further
      reinforced their motivation to quit. Greater focus on why those with SUDs want to
      quit may help direct treatment matching; treatment completion may be more likely
      if the person's reasons for seeking help are addressed.

PMID- 29449780
TI  - Tubular Adenoma of the Breast: A Clinicopathologic Study of a Series of 9 Cases.
AB  - Tubular adenoma of the breast is one of the most rare benign neoplasms,
      accounting for only 0.13% to 1.7% of all breast benign tumors. Little is known
      about this rare neoplasm as the current literature offers only some case reports
      or a few number of small series. The aim of our study is to provide some
      clinicopathologic features of the breast tubular adenoma. We retrospectively
      analyzed at our department of pathology all cases of breast tubular adenomas
      confirmed by immunohistochemistry over a period of 9 years (2009-2017). Nine
      cases of breast tubular adenoma have been recorded, with an average age of 31.44
      years. Five tumors were located at the right side (55.55%), and most cases had
      suspicious aspects on imaging techniques (6 cases out of 9). The diagnosis has
      been made on 5 resected specimens (lumpectomy) and on 4 core needle biopsies. The
      tumor size ranged from 0.9 to 7 cm (mean size of 3.08 cm) and had well
      circumscribed margins with elastic consistency. The histopathologic analysis
      showed a typical pattern of proliferating round and uniform tubules lined by
      regular epithelial cells surrounded by myoepithelial cells, packed in a small
      amount of stroma, highlighted by CD34 immunostaining. Tubular adenoma is a rare
      breast benign neoplasm of young premenopausal women. The radiologic aspects are
      often worrisome and only the histopathologic analysis can achieve the correct
      definitive diagnosis by excluding all potential differential diagnoses.

PMID- 29449779
TI  - Saccharomyces boulardii CNCM I-745 Improves Intestinal Enzyme Function: A Trophic
      Effects Review.
AB  - Several properties of the probiotic medicinal yeast Saccharomyces boulardii CNCM
      I-745 contribute to its efficacy to prevent or treat diarrhoea. Besides
      immunologic effects, pathogen-binding and anti-toxin effects, as well as positive
      effects on the microbiota, S boulardii CNCM I-745 also has pronounced effects on
      digestive enzymes of the brush border membrane, known as trophic effects. The
      latter are the focus of this review. Literature has been reviewed after searching
      Medline and PMC databases. All relevant non-clinical and clinical studies are
      summarized. S. boulardii CNCM I-745 synthesizes and secretes polyamines, which
      have a role in cell proliferation and differentiation. The administration of
      polyamines or S. boulardii CNCM I-745 enhances the expression of intestinal
      digestive enzymes as well as nutrient uptake transporters. The signalling
      mechanisms leading to enzyme activation are not fully understood. However,
      polyamines have direct nucleic acid-binding capacity with regulatory impact. S.
      boulardii CNCM I-745 induces signalling via the mitogen-activated protein kinase
      pathway. In addition, effects on the phosphatidylinositol-3 kinase (PI3K) pathway
      have been reported. As an additional direct effect, S. boulardii CNCM I-745
      secretes certain enzymes, which enhance nutrient acquisition for the yeast and
      the host. The increased availability of digestive enzymes seems to be one of the
      mechanisms by which S. boulardii CNCM I-745 counteracts diarrhoea; however, also
      people with certain enzyme deficiencies may profit from its administration. More
      studies are needed to fully understand the mechanisms of trophic activation by
      the probiotic yeast.

PMID- 29449781
TI  - Whole genome sequencing of multidrug-resistant Salmonella enterica serovar
      Typhimurium isolated from humans and poultry in Burkina Faso.
AB  - Background: Multidrug-resistant Salmonella is an important cause of morbidity and
      mortality in developing countries. The aim of this study was to characterize and
      compare multidrug-resistant Salmonella enterica serovar Typhimurium isolates from
      patients and poultry feces. Methods: Salmonella strains were isolated from
      poultry and patients using standard bacteriological methods described in previous
      studies. The strains were serotype according to Kaufmann-White scheme and tested
      for antibiotic susceptibility to 12 different antimicrobial agents using the disk
      diffusion method. The whole genome of the S. Typhimurium isolates was analyzed
      using Illumina technology and compared with 20 isolates of S. Typhimurium for
      which the ST has been deposited in a global MLST database.The ResFinder Web
      server was used to find the antibiotic resistance genes from whole genome
      sequencing (WGS) data. For comparative genomics, publicly available complete and
      draft genomes of different S. Typhimurium laboratory-adapted strains were
      downloaded from GenBank. Results: All the tested Salmonella serotype Typhimurium
      were multiresistant to five commonly used antibiotics (ampicillin,
      chloramphenicol, streptomycin, sulfonamide, and trimethoprim). The multilocus
      sequence type ST313 was detected from all the strains. Our sequences were very
      similar to S. Typhimurium ST313 strain D23580 isolated from a patient with
      invasive non-typhoid Salmonella (NTS) infection in Malawi, also located in sub
      Saharan Africa. The use of ResFinder web server on the whole genome of the
      strains showed a resistance to aminoglycoside associated with carriage of the
      following resistances genes: strA, strB, and aadA1; resistance to beta-lactams
      associated with carriage of a blaTEM-1B genes; resistance to phenicol associated
      with carriage of catA1 gene; resistance to sulfonamide associated with carriage
      of sul1 and sul2 genes; resistance to tetracycline associated with carriage of
      tet B gene; and resistance to trimethoprim associated to dfrA1 gene for all the
      isolates. Conclusion: The poultry and human isolates were genetically similar
      showing a potential food safety risk for consumers. Our finding of multidrug
      resistant S. Typhimurium ST313 in poultry feces calls for further studies to
      clarify the potential reservoirs of this emerging pathogen.

PMID- 29449782
TI  - Perception of American English vowels by sequential Spanish-English bilinguals.
AB  - Research on American-English (AE) vowel perception by Spanish-English bilinguals
      has focused on the vowels /i/-/i/ (e.g., in sheep/ship). Other AE vowel contrasts
      may present perceptual challenges for this population, especially those requiring
      both spectral and durational discrimination. We used Event-Related Potentials
      (ERPs), MMN (Mismatch Negativity) and P300, to index discrimination of AE vowels
      /alpha/-/v/ by sequential adult Spanish-English bilingual listeners compared to
      AE monolinguals. Listening tasks were non-attended and attended, and vowels were
      presented with natural and neutralized durations. Regardless of vowel duration,
      bilingual listeners showed no MMN to unattended sounds, and P300 responses were
      elicited to /alpha/ but not /v/ in the attended condition. Monolingual listeners
      showed pre-attentive discrimination (MMN) for /alpha/ only; while both vowels
      elicited P300 responses when attended. Findings suggest that Spanish-English
      bilinguals recruit attentional and cognitive resources enabling native-like use
      of both spectral and durational cues to discriminate between AE vowels /alpha/
      and /v/.

PMID- 29449783
TI  - Conducting interactive experiments online.
AB  - Online labor markets provide new opportunities for behavioral research, but
      conducting economic experiments online raises important methodological
      challenges. This particularly holds for interactive designs. In this paper, we
      provide a methodological discussion of the similarities and differences between
      interactive experiments conducted in the laboratory and online. To this end, we
      conduct a repeated public goods experiment with and without punishment using
      samples from the laboratory and the online platform Amazon Mechanical Turk. We
      chose to replicate this experiment because it is long and logistically complex.
      It therefore provides a good case study for discussing the methodological and
      practical challenges of online interactive experimentation. We find that basic
      behavioral patterns of cooperation and punishment in the laboratory are
      replicable online. The most important challenge of online interactive experiments
      is participant dropout. We discuss measures for reducing dropout and show that,
      for our case study, dropouts are exogenous to the experiment. We conclude that
      data quality for interactive experiments via the Internet is adequate and
      reliable, making online interactive experimentation a potentially valuable
      complement to laboratory studies.

PMID- 29449784
TI  - Immaterial and monetary gifts in economic transactions: evidence from the field.
AB  - Reciprocation of monetary gifts is well-understood in economics. In contrast,
      there is little research on reciprocal behavior following immaterial gifts like
      compliments. We narrow this gap and investigate how employees reciprocate after
      receiving immaterial gifts and material gifts over time. We purchase (1) ice
      cream from fast food restaurants, and (2) durum doner, a common lunch snack, from
      independent vendors. Prior to the food's preparation, we either compliment or tip
      the salesperson. We find that salespersons reciprocate compliments with higher
      product weight than in a control treatment. Importantly, this reciprocal behavior
      following immaterial gifts grows over repeated transactions. Tips, in contrast,
      have a stronger level effect which does not change over time.

PMID- 29449785
TI  - A systematic review of burnout among doctors in China: a cultural perspective.
AB  - Background: Numerous studies around the world has already suggested that burnout
      among doctors is a global phenomenon. However, studies for burnout in doctors are
      relatively limited in Chinese communities when compared to the West. As risk
      factors, barriers to intervention and strategies combatting burnout in different
      parts of the world can vary a lot due to different social culture and healthcare
      system, study with a focus at doctors in China from a cultural perspective is a
      worthful endeavor. Methods: Systematic searches of databases were conducted for
      papers published in peer-reviewed journals from 2006 to 2016. Selection criteria
      included practicing doctors in Mainland China and publications written in English
      or Chinese. Keywords searched including "burnout", "doctors" and "China" in 3
      electronic databases has been undergone. Traditional understanding of "work
      attitude" and "doctors' humanity" from ancient Chinese literature has also been
      retrieved. Results: Eleven full papers, including 9302 participants, were
      included in this review. The overall prevalence of burnout symptoms among doctors
      in China ranged from 66.5 to 87.8%. The review suggested that negative impact of
      burnout include association with anxiety symptoms and low job satisfaction at the
      individual doctors' level, and prone to committing medical mistakes affecting
      patient safety and higher turnover intention at the society/organizational level.
      Burnout was higher among doctors who worked over 40 h/week, working in tertiary
      hospitals, on younger age group within the profession (at age 30-40), and with
      negative individual perception to work and life. Conclusions and implications:
      The overall prevalence and adverse impact of burnout among doctors in China echo
      with the findings from Western studies. Young doctors and doctors working in
      tertiary hospitals are more at risk of burnout, probably related to shift of
      social culture related to the loss of medical humanities and a weak primary
      healthcare system. Potential strategies of managing burnout in Chinese doctors
      should therefore take consideration from the Chinese cultural perspective, with
      renaissance of medical humanities and strengthening the primary healthcare system
      in China.

PMID- 29449786
TI  - Impact of the introduction of an endotracheal tube attachment device on the
      incidence and severity of oral pressure injuries in the intensive care unit: a
      retrospective observational study.
AB  - Background: Endotracheal tube (ETT) fasteners such as the AnchorFastTM claim to
      assist with the prevention of oral pressure injuries in intubated patients,
      however evidence to support their clinical efficacy is limited. This
      retrospective observational study aimed to investigate the impact of the
      introduction of the AnchorFastTM device on the incidence of oral pressure
      injuries in mechanically ventilated patients. Methods: Data was collected from
      patient case notes and clinical incident reports for October 2010 to June 2013
      (pre-AnchorFast) and July 2013 to March 2016 (post-AnchorFast). Incidence and
      location of oral pressure injuries associated with securing device, and
      compliance with institutional policies related to reducing oral pressure injuries
      were recorded. Results: Incidence of oral pressure injuries increased from
      1.53/100 intubated patients in the pre-AnchorFast period to 3.73/100 intubated
      patients in the post-AnchorFast period (IRR = 2.43, 95%CI = 1.35-4.38; p =
      0.003). Across both study periods, patients with an ETT secured using
      AnchorFastTM had significantly increased risk of oral pressure injuries (IRR =
      2.03, 95%CI = 1.17-3.51; p = 0.02). There was also a significant difference in
      location of pressure injuries sustained with ETTs secured using cloth tapes
      (53.6% in corner of the mouth) vs. AnchorFastTM (75% on the lips) (p = 0.008).
      Among patients with oral pressure injuries, compliance with institutional
      policies relating to the prevention of pressure injuries was significantly
      greater after the introduction of the AnchorFastTM (9.1% vs 64.5%, p = 0.004).
      Conclusions: The incidence of oral pressure injuries increased significantly
      following the introduction of the AnchorFastTM device. Further research is
      required to establish the reasons for this observed increase to and identify ways
      to reduce the risk of pressure injuries with ETT securement devices.

PMID- 29449787
TI  - Cumulative receiver operating characteristics for analyzing interaction between
      tissue visfatin and clinicopathologic factors in breast cancer progression.
AB  - Background: Visfatin has been reported to be associated with breast cancer
      progression, but the interaction between the visfatin and clinicopathologic
      factors in breast cancer progression status requires further investigation. To
      address this problem, it is better to simultaneously consider multiple factors in
      sensitivity and specificity assays. Methods: In this study, a dataset for 105
      breast cancer patients (84 disease-free and 21 progressing) were chosen.
      Individual and cumulative receiver operating characteristics (ROC) were used to
      analyze the impact of each factor along with interaction effects. Results: In
      individual ROC analysis, only 3 of 13 factors showed better performance for area
      under curve (AUC), i.e., AUC > 7 for hormone therapy (HT), tissue visfatin, and
      lymph node (LN) metastasis. Under our proposed scoring system, the cumulative ROC
      analysis provides higher AUC performance (0.746-0.886) than individual ROC
      analysis in predicting breast cancer progression. Considering the interaction
      between these factors, a minimum of six factors, including HT, tissue visfatin,
      LN metastasis, tumor stage, age, and tumor size, were identified as being highly
      interactive and associated with breast cancer progression, providing potential
      and optimal discriminators for predicting breast cancer progression. Conclusion:
      Taken together, the cumulative ROC analysis provides better prediction for breast
      cancer progression than individual ROC analysis.

PMID- 29449789
TI  - Factors associated with prescribing costs: analysis of a nationwide
      administrative database.
AB  - Objective: All health care systems in the world struggle with rising costs for
      drugs. We sought to explore factors impacting on prescribing costs in a
      nationwide database of ambulatory care in Germany. Factors identified by this
      research can be used for adjustment in future profiling efforts. Methods: We
      analysed nationwide prescription data of physicians having contractual
      relationships with statutory health insurance funds in 2014. Predictor and
      outcome variables were aggregated at the practice level. We performed analyses
      separately for primary care and specialties of cardiology, gastroenterology,
      neurology and psychiatry, pulmology as well as oncology and haematology.
      Bivariate robust regressions and Spearman rank correlations were computed in
      order to find meaningful predictors for our outcome variable prescription costs
      per patient. Results: Median age of patients and proportion of DDD issued were
      substantial predictors for prescription costs per patient in Primary Care,
      Cardiology, and Pulmology with explained variances between 41 and 61%. In
      Neurology and Psychiatry only proportion of patients with polypharmacy >= 2
      quarters was a significant predictor for prescription costs per patient,
      explaining 20% of the variance. For gastroenterologists, oncologists and
      haematologists no stable models could be established. Conclusions: Any analysis
      of prescribing behaviour must take the degree into account to which an individual
      physician or practice is responsible for prescribing patients' medication.
      Proportion of prescriptions/DDDs is an essential confounder for future studies of
      drug prescribing.

PMID- 29449790
TI  - Financial Distress among Pacific Islanders in Southern California.
AB  - Pacific Islanders experience enduring and growing poverty in the United States,
      yet our understanding of their financial distress and needs is limited. Financial
      institutions, government agencies, and community-based organizations in areas
      with large Pacific Islander communities need better information with which to
      develop tailored programs, improve outreach and education, and improve economic
      security for these and other underserved populations. This paper describes the
      results from a unique in-language survey that asked detailed questions regarding
      the financial knowledge, status, and needs of Pacific Islanders, including
      poverty and wealth questions beyond those in the Census, in Los Angeles, Orange,
      and San Diego counties of Southern California.

PMID- 29449788
TI  - RRS1 gene expression involved in the progression of papillary thyroid carcinoma.
AB  - Background: Papillary thyroid carcinoma (PTC) is one of the most frequent
      malignancies of the endocrine system, whose mechanisms of pathogenesis,
      progression and prognosis are still far from being clearly elucidated. Despite an
      increasing body of evidences highlights ribosome biogenesis regulator homolog
      (RRS1) as a ribosome biogenesis protein in yeast and plants, little is known
      about human RRS1 function. Methods: Proliferation, cell cycle and apoptosis of
      PTC cells were assessed following the knockdown of RRS1 expression though MTT,
      colony formation assay, and flow cytometry. Then, transcriptome profiling was
      conducted to explore pathway changes after RRS1 silencing in PTC cells. Receiver
      operating characteristic curve and Youden's index were performed in twenty-four
      thyroid carcinoma samples to assess their potential clinical diagnostic value.
      Results: Firstly, we found that silencing RRS1 significantly reduced cell
      proliferation, inhibited cell cycle, and promoted apoptosis in PTC cell line. The
      result also showed that knock-down of RRS1 could up-regulate genes involving
      apoptosis and metabolism, while, down-regulate genes relative to cell
      proliferation and blood vessel development. Notably, the present study confirmed
      the diagnostic value of RRS1 for thyroid carcinoma in both children and adults.
      Conclusions: In conclusion, these data afford a comprehensive view of a novel
      function of human RRS1 by promoting cell proliferation and could be a potential
      indicator for papillary thyroid carcinoma.

PMID- 29449791
TI  - Influence of acute consumption of caffeine vs. placebo over Bia-derived
      measurements of body composition: a randomized, double-blind, crossover design.
AB  - Background: Bioelectrical impedance analysis (BIA) is often used to estimate
      total body water (TBW), intracellular body water (ICW), extracellular body water
      (ECW), and body fat percentage (BF%). A common restriction for BIA analysis is
      abstinence from caffeine 12-h prior to testing. However, research has yet to
      determine whether the consumption of caffeine influences BIA testing results. The
      purpose of this study was to determine if the consumption of caffeine influences
      BIA-derived BF% and body water values in habitual caffeine users. Methods: Twenty
      apparently healthy males (26.6 +/- 4.1 years) identified as habitual caffeine
      consumers (>= one 95 mg serving per day >= four days per week) participated in
      this study. Participants came to the lab on three occasions, the first visit
      serving as the control (CON) with no supplementation. The remaining two visits
      were performed in a randomized double-blind, cross-over fashion. Participants
      consumed 200 mg of dextrose (PLA) or caffeine (CAF) in capsule form. During each
      visit, seven multi-frequency BIA measurements were conducted before (PRE) and
      after (15-min, 30-min, 45-min, 60-min, 75-min, 90-min) consumption. Results:
      Repeated measures ANOVA revealed BF% for CAF was lower than the CON and PLA
      conditions at PRE and 15-min (p < 0.001, p = 0.004), but not statistically
      significant for the remaining time points (i.e., 30-, 45-, 60-, 75-, and 90-min).
      However, the effect size (ES) of the BF% differences were trivial. The CON, PLA,
      and CAF conditions had higher PRE ICW values than their associated post time
      points (i.e., 15-, 30-, 45-, 60-, 75-, and 90-min). Similar to BF%, ES of the
      mean differences for ICW were trivial. No other differences were observed.
      Conclusion: Caffeine consumption in habitual users produced trivial changes in
      TBW, ECW, ICW, or BF%. Therefore, the pre-testing guidelines for caffeine
      consumption may not be necessary in habitual caffeine consumers.

PMID- 29449792
TI  - Seric concentrations of copper, chromium, manganesum, nickel and selenium in
      aerobic, anaerobic and mixed professional sportsmen.
AB  - Background: The aim of the present study was to determine changes in serum
      concentrations of trace elements Cooper (Cu), Chromiun (Cr), Manganesum (Mn),
      Nickel (Ni) and Selenium (Se) in high-level sportsmen. Methods: Eighty
      professional athletes of different metabolic modalities, were recruited before
      the start of their training period. Thirty one sedentary participants of the same
      geographic area constituted the control group. Cu, Cr, Mn, Ni and Se analysis was
      performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Results:
      Higher concentrations of Cr (p < 0.001), Mn (p < 0.085), and Ni (p < 0.001) were
      found in sportsmen in comparison to controls, inversely, Se values were lower (p
      < 0.001) among sportsmen. When sportsmen were classified by metabolic modalities,
      it was found that aerobic-anaerobic group had higher (p < 0.01) Cu concentrations
      than controls and the other sportsmen. The highest Cr values were found in
      aerobic participants. For Mn, the major levels were found in aerobic and aerobic
      anaerobic groups as well (p < 0.001). The lowest Se levels were found among
      anaerobic sportsmen (p < 0.001). Conclusion: This research showed that daily,
      continuum physical training induced alterations in serum essential minerals
      concentrations, as well as that these changes can be dependent of the exercise
      modality practiced.

PMID- 29449794
TI  - Leveraging annotation-based modeling with Jump.
AB  - The capability of UML profiles to serve as annotation mechanism has been
      recognized in both research and industry. Today's modeling tools offer profiles
      specific to platforms, such as Java, as they facilitate model-based engineering
      approaches. However, considering the large number of possible annotations in
      Java, manually developing the corresponding profiles would only be achievable by
      huge development and maintenance efforts. Thus, leveraging annotation-based
      modeling requires an automated approach capable of generating platform-specific
      profiles from Java libraries. To address this challenge, we present the fully
      automated transformation chain realized by Jump, thereby continuing existing
      mapping efforts between Java and UML by emphasizing on annotations and profiles.
      The evaluation of Jump shows that it scales for large Java libraries and
      generates profiles of equal or even improved quality compared to profiles
      currently used in practice. Furthermore, we demonstrate the practical value of
      Jump by contributing profiles that facilitate reverse engineering and forward
      engineering processes for the Java platform by applying it to a modernization
      scenario.

PMID- 29449793
TI  - Clinical proteomic analysis of scrub typhus infection.
AB  - Background: Scrub typhus is an acute and febrile infectious disease caused by the
      Gram-negative alpha-proteobacterium Orientia tsutsugamushi from the family
      Rickettsiaceae that is widely distributed in Northern, Southern and Eastern Asia.
      In the present study, we analysed the serum proteome of scrub typhus patients to
      investigate specific clinical protein patterns in an attempt to explain
      pathophysiology and discover potential biomarkers of infection. Methods: Serum
      samples were collected from three patients (before and after treatment with
      antibiotics) and three healthy subjects. One-dimensional sodium dodecyl sulphate
      polyacrylamide gel electrophoresis followed by liquid chromatography-tandem mass
      spectrometry was performed to identify differentially abundant proteins using
      quantitative proteomic approaches. Bioinformatic analysis was then performed
      using Ingenuity Pathway Analysis. Results: Proteomic analysis identified 236
      serum proteins, of which 32 were differentially expressed in normal subjects,
      naive scrub typhus patients and patients treated with antibiotics. Comparative
      bioinformatic analysis of the identified proteins revealed up-regulation of
      proteins involved in immune responses, especially complement system, following
      infection with O. tsutsugamushi, and normal expression was largely rescued by
      antibiotic treatment. Conclusions: This is the first proteomic study of clinical
      serum samples from scrub typhus patients. Proteomic analysis identified changes
      in protein expression upon infection with O. tsutsugamushi and following
      antibiotic treatment. Our results provide valuable information for further
      investigation of scrub typhus therapy and diagnosis.

PMID- 29449795
TI  - Foundations for Streaming Model Transformations by Complex Event Processing.
AB  - Streaming model transformations represent a novel class of transformations to
      manipulate models whose elements are continuously produced or modified in high
      volume and with rapid rate of change. Executing streaming transformations
      requires efficient techniques to recognize activated transformation rules over a
      live model and a potentially infinite stream of events. In this paper, we propose
      foundations of streaming model transformations by innovatively integrating
      incremental model query, complex event processing (CEP) and reactive (event
      driven) transformation techniques. Complex event processing allows to identify
      relevant patterns and sequences of events over an event stream. Our approach
      enables event streams to include model change events which are automatically and
      continuously populated by incremental model queries. Furthermore, a reactive rule
      engine carries out transformations on identified complex event patterns. We
      provide an integrated domain-specific language with precise semantics for
      capturing complex event patterns and streaming transformations together with an
      execution engine, all of which is now part of the Viatra reactive transformation
      framework. We demonstrate the feasibility of our approach with two case studies:
      one in an advanced model engineering workflow; and one in the context of on-the
      fly gesture recognition.

PMID- 29449796
TI  - Formalization of the classification pattern: survey of classification modeling in
      information systems engineering.
AB  - Formalization is becoming more common in all stages of the development of
      information systems, as a better understanding of its benefits emerges.
      Classification systems are ubiquitous, no more so than in domain modeling. The
      classification pattern that underlies these systems provides a good case study of
      the move toward formalization in part because it illustrates some of the barriers
      to formalization, including the formal complexity of the pattern and the
      ontological issues surrounding the "one and the many." Powersets are a way of
      characterizing the (complex) formal structure of the classification pattern, and
      their formalization has been extensively studied in mathematics since Cantor's
      work in the late nineteenth century. One can use this formalization to develop a
      useful benchmark. There are various communities within information systems
      engineering (ISE) that are gradually working toward a formalization of the
      classification pattern. However, for most of these communities, this work is
      incomplete, in that they have not yet arrived at a solution with the
      expressiveness of the powerset benchmark. This contrasts with the early smooth
      adoption of powerset by other information systems communities to, for example,
      formalize relations. One way of understanding the varying rates of adoption is
      recognizing that the different communities have different historical baggage.
      Many conceptual modeling communities emerged from work done on database design,
      and this creates hurdles to the adoption of the high level of expressiveness of
      powersets. Another relevant factor is that these communities also often feel,
      particularly in the case of domain modeling, a responsibility to explain the
      semantics of whatever formal structures they adopt. This paper aims to make sense
      of the formalization of the classification pattern in ISE and surveys its history
      through the literature, starting from the relevant theoretical works of the
      mathematical literature and gradually shifting focus to the ISE literature. The
      literature survey follows the evolution of ISE's understanding of how to
      formalize the classification pattern. The various proposals are assessed using
      the classical example of classification; the Linnaean taxonomy formalized using
      powersets as a benchmark for formal expressiveness. The broad conclusion of the
      survey is that (1) the ISE community is currently in the early stages of the
      process of understanding how to formalize the classification pattern,
      particularly in the requirements for expressiveness exemplified by powersets, and
      (2) that there is an opportunity to intervene and speed up the process of
      adoption by clarifying this expressiveness. Given the central place that the
      classification pattern has in domain modeling, this intervention has the
      potential to lead to significant improvements.

PMID- 29449797
TI  - Dual deep modeling: multi-level modeling with dual potencies and its
      formalization in F-Logic.
AB  - An enterprise database contains a global, integrated, and consistent
      representation of a company's data. Multi-level modeling facilitates the
      definition and maintenance of such an integrated conceptual data model in a
      dynamic environment of changing data requirements of diverse applications. Multi
      level models transcend the traditional separation of class and object with
      clabjects as the central modeling primitive, which allows for a more flexible and
      natural representation of many real-world use cases. In deep instantiation, the
      number of instantiation levels of a clabject or property is indicated by a single
      potency. Dual deep modeling (DDM) differentiates between source potency and
      target potency of a property or association and supports the flexible
      instantiation and refinement of the property by statements connecting clabjects
      at different modeling levels. DDM comes with multiple generalization of
      clabjects, subsetting/specialization of properties, and multi-level cardinality
      constraints. Examples are presented using a UML-style notation for DDM together
      with UML class and object diagrams for the representation of two-level user views
      derived from the multi-level model. Syntax and semantics of DDM are formalized
      and implemented in F-Logic, supporting the modeler with integrity checks and rich
      query facilities.

PMID- 29449799
TI  - Markov Switching Model for Quick Detection of Event Related Desynchronization in
      EEG.
AB  - Quick detection of motor intentions is critical in order to minimize the time
      required to activate a neuroprosthesis. We propose a Markov Switching Model (MSM)
      to achieve quick detection of an event related desynchronization (ERD) elicited
      by motor imagery (MI) and recorded by electroencephalography (EEG). Conventional
      brain computer interfaces (BCI) rely on sliding window classifiers in order to
      perform online continuous classification of the rest vs. MI classes. Based on
      this approach, the detection of abrupt changes in the sensorimotor power suffers
      from an intrinsic delay caused by the necessity of computing an estimate of
      variance across several tenths of a second. Here we propose to avoid explicitly
      computing the EEG signal variance, and estimate the ERD state directly from the
      voltage information, in order to reduce the detection latency. This is achieved
      by using a model suitable in situations characterized by abrupt changes of state,
      the MSM. In our implementation, the model takes the form of a Gaussian
      observation model whose variance is governed by two latent discrete states with
      Markovian dynamics. Its objective is to estimate the brain state (i.e., rest vs.
      ERD) given the EEG voltage, spatially filtered by common spatial pattern (CSP),
      as observation. The two variances associated with the two latent states are
      calibrated using the variance of the CSP projection during rest and MI,
      respectively. The transition matrix of the latent states is optimized by the
      "quickest detection" strategy that minimizes a cost function of detection latency
      and false positive rate. Data collected by a dry EEG system from 50 healthy
      subjects, was used to assess performance and compare the MSM with several
      logistic regression classifiers of different sliding window lengths. As a result,
      the MSM achieves a significantly better tradeoff between latency, false positive
      and true positive rates. The proposed model could be used to achieve a more
      reactive and stable control of a neuroprosthesis. This is a desirable property in
      BCI-based neurorehabilitation, where proprioceptive feedback is provided based on
      the patient's brain signal. Indeed, it is hypothesized that simultaneous
      contingent association between brain signals and proprioceptive feedback induces
      superior associative learning.

PMID- 29449798
TI  - DNA-Methylation: Master or Slave of Neural Fate Decisions?
AB  - The pristine formation of complex organs depends on sharp temporal and spatial
      control of gene expression. Therefore, epigenetic mechanisms have been frequently
      attributed a central role in controlling cell fate determination. A prime example
      for this is the first discovered and still most studied epigenetic mark, DNA
      methylation, and the development of the most complex mammalian organ, the brain.
      Recently, the field of epigenetics has advanced significantly: new DNA
      modifications were discovered, epigenomic profiling became widely accessible, and
      methods for targeted epigenomic manipulation have been developed. Thus, it is
      time to challenge established models of epigenetic gene regulation. Here, we
      review the current state of knowledge about DNA modifications, their epigenomic
      distribution, and their regulatory role. We will summarize the evidence
      suggesting they possess crucial roles in neurogenesis and discuss whether this
      likely includes lineage choice regulation or rather effects on differentiation.
      Finally, we will attempt an outlook on how questions, which remain unresolved,
      could be answered soon.

PMID- 29449800
TI  - Robustness and Vulnerability of the Autoregulatory System That Maintains Nuclear
      TDP-43 Levels: A Trade-off Hypothesis for ALS Pathology Based on in Silico Data.
AB  - Abnormal accumulation of TAR DNA-binding protein 43 (TDP-43) in the cytoplasm and
      its disappearance from the nucleus are pathological features of amyotrophic
      lateral sclerosis and frontotemporal dementia (ALS/FTD) and are directly involved
      in the pathogenesis of these conditions. TDP-43 is an essential nuclear protein
      that readily aggregates in a concentration-dependent manner. Therefore, cells
      must strictly maintain an appropriate amount of nuclear TDP-43. In one relevant
      maintenance mechanism, TDP-43 binds to its pre-mRNA and promotes alternative
      splicing, resulting in mRNA degradation via nonsense-mediated mRNA decay. The
      level of nuclear TDP-43 is tightly regulated by these mechanisms, which control
      the amount of mRNA that may be translated. Based on the results of previous
      experiments, we developed an in silico model that mimics the intracellular
      dynamics of TDP-43 and examined TDP-43 metabolism under various conditions. We
      discovered an inherent trade-off in this mechanism between transcriptional
      redundancy, which maintains the robustness of TDP-43 metabolism, and
      vulnerability to specific interfering factors. These factors include an increased
      tendency of TDP-43 to aggregate, impaired nuclear-cytoplasmic TDP-43 transport,
      and a decreased efficiency of degrading abnormal proteins, all of which are
      functional abnormalities related to the gene that causes familial ALS/FTD. When
      these conditions continue at a certain intensity, the vulnerability of the
      autoregulatory machinery becomes apparent over time, and transcriptional
      redundancy enters a vicious cycle that ultimately results in TDP-43 pathology.
      The results obtained using this in silico model reveal the difference in TDP-43
      metabolism between normal and disease states. Furthermore, using this model, we
      simulated the effect of a decrease in TDP-43 transcription and found that this
      decrease improved TDP-43 pathology and suppressed the abnormal propagation of TDP
      43. Therefore, we propose a potential therapeutic strategy to suppress
      transcriptional redundancy, which is the driving force of the pathological
      condition caused by the specific factors described above, in patients with ALS
      presenting with TDP-43 pathology. An ALS animal model exhibiting TDP-43 pathology
      without overexpression of exogenous TDP-43 should be developed to investigate the
      effect of alleviating the transcriptional redundancy of TARDBP.

PMID- 29449801
TI  - Lithium Inhibits GSK3beta and Augments GluN2A Receptor Expression in the
      Prefrontal Cortex.
AB  - Glycogen synthase kinase 3beta (GSK3beta) is a highly conserved serine/threonine
      kinase that has been implicated in both psychiatric and neurodegenerative
      diseases including schizophrenia, bipolar disorder, and Alzheimer's disease;
      therefore regulating its activity has become an important strategy for treatment
      of cognitive impairments in these disorders. This study examines the effects of
      lithium on GSK3beta and its interaction with beta-catenin and NMDA receptors
      within the prefrontal cortex. Lithium, a clinically relevant drug commonly
      prescribed as a mood stabilizer for psychiatric disorders, significantly
      increased levels of phosphorylated GSK3beta serine 9, an inhibitory
      phosphorylation site, and decreased beta-catenin ser33/37/thr41 phosphorylation
      in vitro, indicating GSK3beta inhibition and reduced beta-catenin degradation.
      GluN2A subunit levels were concurrently increased following lithium treatment.
      Similar alterations were also demonstrated in vivo; lithium administration
      increased GSK3beta serine 9 phosphorylation and GluN2A levels, suggesting a
      reduced GSK3beta activity and augmented GluN2A expression. Correspondingly, we
      observed that the amplitudes of evoked GluN2A-mediated excitatory postsynaptic
      currents in mPFC pyramidal neurons were significantly increased following lithium
      administration. Our data suggest that GSK3beta activity negatively regulates
      GluN2A expression, likely by mediating upstream beta-catenin phosphorylation, in
      prefrontal cortical neurons. Furthermore, our biochemical and
      electrophysiological experiments demonstrate that lithium mediates a specific
      increase in GluN2A subunit expression, ultimately augmenting GluN2A-mediated
      currents in the prefrontal cortex.

PMID- 29449802
TI  - SPARC and GluA1-Containing AMPA Receptors Promote Neuronal Health Following CNS
      Injury.
AB  - The proper formation and maintenance of functional synapses in the central
      nervous system (CNS) requires communication between neurons and astrocytes and
      the ability of astrocytes to release neuromodulatory molecules. Previously, we
      described a novel role for the astrocyte-secreted matricellular protein SPARC
      (Secreted Protein, Acidic and Rich in Cysteine) in regulating alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and plasticity at
      developing synapses. SPARC is highly expressed by astrocytes and microglia during
      CNS development but its level is reduced in adulthood. Interestingly, SPARC has
      been shown to be upregulated in CNS injury and disease. However, the role of
      SPARC upregulation in these contexts is not fully understood. In this study, we
      investigated the effect of chronic SPARC administration on glutamate receptors on
      mature hippocampal neuron cultures and following CNS injury. We found that SPARC
      treatment increased the number of GluA1-containing AMPARs at synapses and
      enhanced synaptic function. Furthermore, we determined that the increase in
      synaptic strength induced by SPARC could be inhibited by Philanthotoxin-433, a
      blocker of homomeric GluA1-containing AMPARs. We then investigated the effect of
      SPARC treatment on neuronal health in an injury context where SPARC expression is
      upregulated. We found that SPARC levels are increased in astrocytes and microglia
      following middle cerebral artery occlusion (MCAO) in vivo and oxygen-glucose
      deprivation (OGD) in vitro. Remarkably, chronic pre-treatment with SPARC
      prevented OGD-induced loss of synaptic GluA1. Furthermore, SPARC treatment
      reduced neuronal death through Philanthotoxin-433 sensitive GluA1 receptors.
      Taken together, this study suggests a novel role for SPARC and GluA1 in promoting
      neuronal health and recovery following CNS damage.

PMID- 29449804
TI  - An Early Sensitive Period Induces Long-Lasting Plasticity in the Honeybee Nervous
      System.
AB  - The effect of early experiences on the brain during a sensitive period exerts a
      long-lasting influence on the mature individual. Despite behavioral and neural
      plasticity caused by early experiences having been reported in the honeybee Apis
      mellifera, the presence of a sensitive period in which associative experiences
      lead to pronounced modifications in the adult nervous system is still unclear.
      Laboratory-reared bees were fed with scented food within specific temporal
      windows and were assessed for memory retention, in the regulation of gene
      expression related to the synaptic formation and in the olfactory perception of
      their antennae at 17 days of age. Bees were able to retain a food-odor
      association acquired 5-8 days after emergence, but not before, and showed better
      retention than those exposed to an odor at 9-12 days. In the brain, the odor
      rewarded experiences that occurred at 5-8 days of age boosted the expression
      levels of the cell adhesion proteins neurexin 1 (Nrx1) and neuroligin 2 (Nlg2)
      involved in synaptic strength. At the antennae, the experiences increased the
      electrical response to a novel odor but not to the one experienced. Therefore, a
      sensitive period that induces long-lasting behavioral, functional and structural
      changes is found in adult honeybees.

PMID- 29449805
TI  - Screen Position Preference Offers a New Direction for Action Observation
      Research: Preliminary Findings Using TMS.
AB  - Action observation has been suggested to be an effective adjunct to physical
      practice in motor (re)learning settings. However, optimal viewing conditions for
      interventions are yet to be established. Single-pulse transcranial magnetic
      stimulation (TMS) was used to investigate the effect of two different screen
      positions and participants' screen position viewing preference on the amplitude
      of motor evoked potentials (MEPs) during observation of a ball pinch action.
      Twenty-four participants observed four blocked conditions that contained either a
      dynamic index finger-thumb ball pinch or a static hand holding a ball in a
      similar position on a horizontally or vertically positioned screen. TMS was
      delivered to the hand representation of the left primary motor cortex and MEPs
      were recorded from the first dorsal interosseous muscle of the right hand.
      Initial analysis of the normalized MEP amplitude data showed no significant
      differences between conditions. In a follow-up procedure, participants engaged in
      individual semi-structured interviews and completed a questionnaire designed to
      assess viewing affect and screen position viewing preference. The MEP data were
      subsequently split by screen position preference and re-analyzed using a 2 * 2
      repeated measures ANOVA. Main effects indicated that participants who preferred
      the horizontal screen position (n = 16) demonstrated significantly greater MEP
      amplitudes during observation of the ball-pinch action compared to the static
      hand condition irrespective of screen position, and during the horizontal
      compared to the vertical screen position irrespective of video type. These
      results suggest that ensuring anatomical and perceptual congruency with the
      physical task, alongside consideration of participants' screen position viewing
      preferences, may be an important part of optimizing action observation
      interventions.

PMID- 29449806
TI  - Monitoring Attention in ADHD with an Easy-to-Use Electrophysiological Index.
AB  - Attention deficit hyperactivity disorder (ADHD) involves characteristic
      electroencephalographic (EEG) activity. We developed a single-channel EEG marker
      for attention: the Brain Engagement Index (BEI'). In this study, we evaluated the
      use of BEI' for distinguishing between ADHD patients and controls, and for
      monitoring the effect of pharmacological treatment on ADHD patients. The BEI'
      values of 20 ADHD patients and 10 controls were measured using a 1-min auditory
      oddball paradigm and a continuous performance test (CPT) task. We showed that CPT
      BEI' is trait-specific and separates controls from ADHD patients. At the same
      time, oddball BEI' is state-specific and identifies differences in attention
      level within the two groups of ADHD participants and controls. The oddball BEI'
      also associates with response to treatment, after distinguishing between
      treatment effect and learning/time effect. The combined use of this marker with
      common computerized tests holds promise for research and clinical use in ADHD.
      Further work is required to confirm the results of the present study.

PMID- 29449803
TI  - The Consequences of Preterm Birth and Chorioamnionitis on Brainstem Respiratory
      Centers: Implications for Neurochemical Development and Altered Functions by
      Inflammation and Prostaglandins.
AB  - Preterm birth is a major cause for neonatal morbidity and mortality, and is
      frequently associated with adverse neurological outcomes. The transition from
      intrauterine to extrauterine life at birth is particularly challenging for
      preterm infants. The main physiological driver for extrauterine transition is the
      establishment of spontaneous breathing. However, preterm infants have difficulty
      clearing lung liquid, have insufficient surfactant levels, and underdeveloped
      lungs. Further, preterm infants have an underdeveloped brainstem, resulting in
      reduced respiratory drive. These factors facilitate the increased requirement for
      respiratory support. A principal cause of preterm birth is intrauterine
      infection/inflammation (chorioamnionitis), and infants with chorioamnionitis have
      an increased risk and severity of neurological damage, but also demonstrate
      impaired autoresuscitation capacity and prevalent apnoeic episodes. The brainstem
      contains vital respiratory centers which provide the neural drive for breathing,
      but the impact of preterm birth and/or chorioamnionitis on this brain region is
      not well understood. The aim of this review is to provide an overview of the role
      and function of the brainstem respiratory centers, and to highlight the proposed
      mechanisms of how preterm birth and chorioamnionitis may affect central
      respiratory functions.

PMID- 29449807
TI  - Atrial Natriuretic Peptide Acts as a Neuroprotective Agent in in Vitro Models of
      Parkinson's Disease via Up-regulation of the Wnt/beta-Catenin Pathway.
AB  - In the last decades increasing evidence indicated a crucial role of the Wnt/beta
      catenin signaling in development of midbrain dopaminergic (mDA) neurons. Recently
      dysregulation of this pathway has been proposed as a novel pathomechanism leading
      to Parkinson's disease (PD) and some of the molecules participating to the
      signaling have been evaluated as potential therapeutic targets for PD. Atrial
      natriuretic peptide (ANP) is a cardiac-derived hormone having a critical role in
      cardiovascular homeostasis. ANP and its receptors (NPRs) are widely expressed in
      mammalian central nervous system (CNS) where they could be implicated in the
      regulation of neural development, synaptic transmission and information
      processing, as well as in neuroprotection. Until now, the effects of ANP in the
      CNS have been mainly ascribed to the binding and activation of NPRs. We have
      previously demonstrated that ANP affects the Wnt/beta-catenin signaling in
      colorectal cancer cells through a Frizzled receptor-mediated mechanism. The
      purpose of this study was to investigate if ANP is able to exert neuroprotective
      effect on two in vitro models of PD, and if this effect could be related to
      activation of the Wnt/beta-catenin signaling. As cellular models of DA neurons,
      we used the proliferating or RA-differentiated human neuroblastoma cell line SH
      SY5Y. In both DA neuron-like cultures, ANP is able to positively affect the
      Wnt/beta-catenin signaling, by inducing beta-catenin stabilization and nuclear
      translocation. Importantly, activation of the Wnt pathway by ANP exerts
      neuroprotective effect when these two cellular systems were subjected to
      neurotoxic insult (6-OHDA) for mimicking the neurodegeneration of PD. Our data
      support the relevance of exogenous ANP as an innovative therapeutic molecule for
      midbrain, and more in general for brain diseases for which aberrant Wnt signaling
      seems to be involved.

PMID- 29449808
TI  - Suppressive Effects of Clerodendrum volubile P Beauv. [Labiatae] Methanolic
      Extract and Its Fractions on Type 2 Diabetes and Its Complications.
AB  - Type 2 diabetes is the most prominent of all diabetes types, contributing to
      global morbidity and mortality. Availability and cost of treatment with little or
      no side effect especially in developing countries, remains a huge burden. This
      has led to the search of affordable alternative therapies especially from
      medicinal plants. In this study, the antidiabetic effect of the methanolic
      extract, dichloromethane (DCM), butanol (BuOH) and aqueous fractions of
      Clerodendrum volubile leaves were investigated in type 2 diabetic rats for their
      effect on glucose homeostasis, serum insulin level and hepatic biomarkers, lipid
      profile, pancreatic redox balance and Ca2+ levels, and beta-cell distribution and
      function. The DCM was further fractionated to isolate the active compounds,
      biochanin and 5,7,4'-trimethoxykaempferol. They were investigated for their
      toxicity and ADMET properties, alpha-glucosidase and angiotensin I converting
      enzyme (ACE) inhibitory activities in silico. There were significant (p < 0.05)
      decrease in blood glucose, cholesterol, LDL-C, vLDL-C, triglyceride, AST and ALT
      levels in all treated groups, with DCM fraction showing the best activity. All
      treated rats showed significantly (p < 0.05) improved anti-oxidative activities.
      Treatment with the DCM fraction led to significant (p < 0.05) increased serum
      insulin and pancreatic Ca2+ levels, as well as improved beta-cell distribution
      and function. DCM fraction also showed improved glucose tolerance. DCM fraction
      dose-dependently inhibited ACE activity. The toxicity class of the isolated
      compounds was predicted to be 5. They were also predicted to be potent inhibitors
      of cytochrome P (CYPs) 1A2, 2D6 and 3A4. They docked well with alpha-glucosidase
      and ACE. These results indicate the therapeutic potential of the plant against
      type 2 diabetes, with the DCM fraction being the most potent which may be
      attributed to the isolated flavones. It further suggests antihypertensive
      potentials of the DCM fraction. However, inhibition of CYPs by the flavones may
      suggest caution in usage with other prescribed drugs metabolized by these
      enzymes.

PMID- 29449809
TI  - Digging into Lipid Membrane Permeation for Cardiac Ion Channel Blocker d-Sotalol
      with All-Atom Simulations.
AB  - Interactions of drug molecules with lipid membranes play crucial role in their
      accessibility of cellular targets and can be an important predictor of their
      therapeutic and safety profiles. Very little is known about spatial localization
      of various drugs in the lipid bilayers, their active form (ionization state) or
      translocation rates and therefore potency to bind to different sites in membrane
      proteins. All-atom molecular simulations may help to map drug partitioning
      kinetics and thermodynamics, thus providing in-depth assessment of drug
      lipophilicity. As a proof of principle, we evaluated extensively lipid membrane
      partitioning of d-sotalol, well-known blocker of a cardiac potassium channel
      Kv11.1 encoded by the hERG gene, with reported substantial proclivity for
      arrhythmogenesis. We developed the positively charged (cationic) and neutral d
      sotalol models, compatible with the biomolecular CHARMM force field, and
      subjected them to all-atom molecular dynamics (MD) simulations of drug
      partitioning through hydrated lipid membranes, aiming to elucidate thermodynamics
      and kinetics of their translocation and thus putative propensities for
      hydrophobic and aqueous hERG access. We found that only a neutral form of d
      sotalol accumulates in the membrane interior and can move across the bilayer
      within millisecond time scale, and can be relevant to a lipophilic channel
      access. The computed water-membrane partitioning coefficient for this form is in
      good agreement with experiment. There is a large energetic barrier for a cationic
      form of the drug, dominant in water, to cross the membrane, resulting in slow
      membrane translocation kinetics. However, this form of the drug can be important
      for an aqueous access pathway through the intracellular gate of hERG. This route
      will likely occur after a neutral form of a drug crosses the membrane and
      subsequently re-protonates. Our study serves to demonstrate a first step toward a
      framework for multi-scale in silico safety pharmacology, and identifies some of
      the challenges that lie therein.

PMID- 29449810
TI  - Recent Advances in CNS P2X7 Physiology and Pharmacology: Focus on
      Neuropsychiatric Disorders.
AB  - The ATP-gated P2X7 ion channel is an abundant microglial protein in the CNS that
      plays an important pathological role in executing ATP-driven danger signal
      transduction. Emerging data has generated scientific interest and excitement
      around targeting the P2X7 ion channel as a potential drug target for CNS
      disorders. Over the past years, a wealth of data has been published on CNS P2X7
      biology, in particular the role of P2X7 in microglial cells, and in vivo effects
      of brain-penetrant P2X7 antagonists. Likewise, significant progress has been made
      around the medicinal chemistry of CNS P2X7 ligands, as antagonists for in vivo
      target validation in models of CNS diseases, to identification of two clinical
      compounds (JNJ-54175446 and JNJ-55308942) and finally, discovery of P2X7 PET
      ligands. This review is an attempt to bring together the current understanding of
      P2X7 in the CNS with a focus on P2X7 as a drug target in neuropsychiatric
      disorders.

PMID- 29449811
TI  - HDAC6 Inhibition Promotes Transcription Factor EB Activation and Is Protective in
      Experimental Kidney Disease.
AB  - To contend with the deleterious effects of accumulating misfolded protein
      aggregates or damaged organelles cells rely on a system of quality control
      processes, among them the autophagy-lysosome pathway. This pathway is itself
      controlled by a master regulator transcription factor termed transcription factor
      EB (TFEB). When TFEB localizes to the cell nucleus it promotes the expression of
      a number of genes involved in protein clearance. Here, we set out to determine
      (1) whether TFEB expression is altered in chronic kidney disease (CKD); (2)
      whether inhibition of the cytosolic deacetylase histone deacetylase 6 (HDAC6)
      affects TFEB acetylation and nuclear localization; and (3) whether HDAC6
      inhibition, in turn, alters the natural history of experimental CKD. TFEB mRNA
      and protein levels were observed to be diminished in the kidneys of humans with
      diabetic kidney disease, accompanied by accumulation of the protein aggregate
      adaptor protein p62 in tubule epithelial cells. In cultured NRK-52E cells, HDAC6
      inhibition with the small molecule inhibitor Tubastatin A acetylated TFEB,
      increasing TFEB localization to the nucleus and attenuating cell death. In a rat
      model of CKD, Tubastatin A prevented the accumulation of misfolded protein
      aggregates in tubule epithelial cells, attenuated proteinuria progression,
      limited tubule cell death and diminished tubulointerstitial collagenous matrix
      deposition. These findings point to the common occurrence of dysregulated quality
      control processes in CKD and they suggest that TFEB downregulation may contribute
      to tubule injury in CKD. They also identify a regulatory relationship between
      HDAC6 and TFEB. HDAC6 inhibitors and TFEB activators both warrant further
      investigation as treatments for CKD.

PMID- 29449812
TI  - Calycosin Orchestrates Osteogenesis of Danggui Buxue Tang in Cultured
      Osteoblasts: Evaluating the Mechanism of Action by Omics and Chemical Knock-out
      Methodologies.
AB  - Danggui Buxue Tang (DBT), an ancient Chinese herbal decoction commonly used to
      mitigate menopausal osteoporosis, contains two herbs: Astragali Radix (AR) and
      Angelicae Sinensis Radix (ASR). The exact efficacy of individual chemical(s)
      within DBT, or in any herbal mixture, is hard to be revealed. Calycosin and
      ferulic acid have been reported to be the predominant chemicals found within DBT,
      and its roles in regulating osteoblastic differentiation have been proposed here.
      To probe the roles of calycosin and ferulic acid, these chemicals were
      specifically depleted from the DBT extracts. Here, calycosin-depleted DBT
      (DBTDeltacal) and ferulic acid-depleted DBT (DBTDeltafa), generated by semi
      preparative HPLC, were coupled with RNA-seq and metabolomics analyses to reveal
      the synergistic functions of individual chemicals within a complex herbal
      mixture. The expressions of osteogenic differentiation markers were significantly
      increased under the treatments of DBT and DBTDeltafa. The DBT-induced genes were
      markedly reduced in the absent of calycosin, i.e., DBTDeltacal. In cultured
      osteoblasts, the DBT-activated Wnt/beta-catenin and MAPK/Erk and signaling
      pathways were greatly affected when calycosin was depleted. By metabolomics
      analysis in DBT-treated osteoblasts, the profile of metabolites triggered by
      DBTDeltacal showed distinction to that of DBT and/or DBTDeltafa. Thus, our
      findings indicated that calycosin, rather than ferulic acid, could be an
      indispensable chemical in DBT to orchestrate multi-components of DBT in achieving
      maximal osteogenic properties.

PMID- 29449813
TI  - Non-nucleotide Agonists Triggering P2X7 Receptor Activation and Pore Formation.
AB  - The P2X7 receptor (P2X7R) is a ligand-gated plasma membrane ion channel belonging
      to the P2X receptor subfamily activated by extracellular nucleotides. General
      consensus holds that the physiological (and maybe the only) agonist is ATP.
      However, scattered evidence generated over the last several years suggests that
      ATP might not be the only agonist, especially at inflammatory sites. Solid data
      show that NAD+ covalently modifies the P2X7R of mouse T lymphocytes, thus
      lowering the ATP threshold for activation. Other structurally unrelated agents
      have been reported to activate the P2X7R via a poorly understood mechanism of
      action: (a) the antibiotic polymyxin B, possibly a positive allosteric P2X7R
      modulator, (b) the bactericidal peptide LL-37, (c) the amyloidogenic beta
      peptide, and (d) serum amyloid A. Some agents, such as Alu-RNA, have been
      suggested to activate the P2X7R acting on the intracellular N- or C-terminal
      domains. Mode of P2X7R activation by these non-nucleotide ligands is as yet
      unknown; however, these observations raise the intriguing question of how these
      different non-nucleotide ligands may co-operate with ATP at inflammatory or tumor
      sites. New information obtained from the cloning and characterization of the
      P2X7R from exotic mammalian species (e.g., giant panda) and data from recent
      patch-clamp studies are strongly accelerating our understanding of P2X7R mode of
      operation, and may provide hints to the mechanism of activation of P2X7R by non
      nucleotide ligands.

PMID- 29449814
TI  - Multisite Delayed Feedback for Electrical Brain Stimulation.
AB  - Demand-controlled deep brain stimulation (DBS) appears to be a promising approach
      for the treatment of Parkinson's disease (PD) as revealed by computational, pre
      clinical and clinical studies. Stimulation delivery is adapted to brain activity,
      for example, to the amount of neuronal activity considered to be abnormal. Such a
      closed-loop stimulation setup might help to reduce the amount of stimulation
      current, thereby maintaining therapeutic efficacy. In the context of the
      development of stimulation techniques that aim to restore desynchronized neuronal
      activity on a long-term basis, specific closed-loop stimulation protocols were
      designed computationally. These feedback techniques, e.g., pulsatile linear
      delayed feedback (LDF) or pulsatile nonlinear delayed feedback (NDF), were
      computationally developed to counteract abnormal neuronal synchronization
      characteristic for PD and other neurological disorders. By design, these
      techniques are intrinsically demand-controlled methods, where the amplitude of
      the stimulation signal is reduced when the desired desynchronized regime is
      reached. We here introduce a novel demand-controlled stimulation method,
      pulsatile multisite linear delayed feedback (MLDF), by employing MLDF to modulate
      the pulse amplitude of high-frequency (HF) DBS, in this way aiming at a specific,
      MLDF-related desynchronizing impact, while maintaining safety requirements with
      the charge-balanced HF DBS. Previously, MLDF was computationally developed for
      the control of spatio-temporal synchronized patterns and cluster states in
      neuronal populations. Here, in a physiologically motivated model network
      comprising neurons from subthalamic nucleus (STN) and external globus pallidus
      (GPe), we compare pulsatile MLDF to pulsatile LDF for the case where the smooth
      feedback signals are used to modulate the amplitude of charge-balanced HF DBS and
      suggest a modification of pulsatile MLDF which enables a pronounced
      desynchronizing impact. Our results may contribute to further clinical
      development of closed-loop DBS techniques.

PMID- 29449815
TI  - Combinatorial Codes and Labeled Lines: How Insects Use Olfactory Cues to Find and
      Judge Food, Mates, and Oviposition Sites in Complex Environments.
AB  - Insects, including those which provide vital ecosystems services as well as those
      which are devastating pests or disease vectors, locate their resources mainly
      based on olfaction. Understanding insect olfaction not only from a
      neurobiological but also from an ecological perspective is therefore crucial to
      balance insect control and conservation. However, among all sensory stimuli
      olfaction is particularly hard to grasp. Our chemical environment is made up of
      thousands of different compounds, which might again be detected by our nose in
      multiple ways. Due to this complexity, researchers have only recently begun to
      explore the chemosensory ecology of model organisms such as Drosophila, linking
      the tools of chemical ecology to those of neurogenetics. This cross-disciplinary
      approach has enabled several studies that range from single odors and their
      ecological relevance, via olfactory receptor genes and neuronal processing, up to
      the insects' behavior. We learned that the insect olfactory system employs
      strategies of combinatorial coding to process general odors as well as labeled
      lines for specific compounds that call for an immediate response. These studies
      opened new doors to the olfactory world in which insects feed, oviposit, and
      mate.

PMID- 29449817
TI  - Clinical Factors Associated with Brain Volume Reduction in Systemic Lupus
      Erythematosus Patients without Major Neuropsychiatric Manifestations.
AB  - The aim of the study was to find structural brain changes in systemic lupus
      erythematosus patients without major neuropsychiatric manifestations [non
      neuropsychiatric systemic lupus erythematosus (non-NPSLE)] using quantitative
      magnetic resonance imaging (MRI) and possible associations with clinical
      characteristics. 89 non-NPSLE patients with normal conventional MRI and 84
      healthy controls (HCs) were recruited. The whole brain gray matter volume (GMV)
      and white matter volume (WMV) were calculated for each individual. We found
      obvious GMV and WMV reduction in the systemic lupus erythematosus (SLE) group
      compared with HCs. Female patients showed significant reduction of GMV and WMV
      compared with male patients. Patients treated with immunosuppressive agents (ISA)
      showed less WMV reduction than those without. Cognitive impairment was the most
      common subclinical neuropsychiatric manifestation and had a prevalence of 46.1%.
      Association between WMV reduction with cognitive impairment was found. Thus, we
      concluded that structural brain atrophy could happen even before occurrence of
      obvious neuropsychiatric signs and symptoms and was associated with subclinical
      symptoms such as cognitive impairment. ISA treatment might have a protective
      effect on the brain atrophy. Early treatment might prevent the progressive damage
      to the brain. More studies are needed to fully understand the complicated
      underlying mechanisms of brain atrophy in SLE.

PMID- 29449818
TI  - Is Reading Instruction Evidence-Based? Analyzing Teaching Practices Using T
      Patterns.
AB  - The main goal of this study was to analyze whether primary teachers use evidence
      based reading instruction for primary-grade readers. The study sample consisted
      of six teachers whose teaching was recorded. The observation instrument used was
      developed ad hoc for this study. The recording instrument used was Match Vision
      Studio. The data analysis was performed using SAS, GT version 2.0 E, and THEME.
      The results indicated that the teaching practices used most frequently and for
      the longest duration were: feedback (i.e., correcting the student when reading);
      fluency (i.e., individual and group reading, both out loud and silently, with and
      without intonation); literal or inference comprehension exercises (i.e.,
      summarizing, asking questions); and use of educational resources (i.e., stories,
      songs, poems). Later, we conducted analyses of T-Patterns that showed the
      sequence of instruction in detail. We can conclude that <50% of the teaching
      practices used by the majority of teachers were based on the recommendations of
      the National Reading Panel (NRP). Only one teacher followed best practices. The
      same was the case for instructional time spent on the five essential components
      of reading, with the exception of teacher E., who dedicated 70.31% of class time
      implementing best practices. Teaching practices (i.e., learners' activities)
      designed and implemented to exercise and master alphabetic knowledge and
      phonological awareness skills were used less frequently in the classroom.

PMID- 29449819
TI  - Knowledge Is Power for Medical Assistants: Crystallized and Fluid Intelligence As
      Predictors of Vocational Knowledge.
AB  - Medical education research has focused almost entirely on the education of future
      physicians. In comparison, findings on other health-related occupations, such as
      medical assistants, are scarce. With the current study, we wanted to examine the
      knowledge-is-power hypothesis in a real life educational setting and add to the
      sparse literature on medical assistants. Acquisition of vocational knowledge in
      vocational education and training (VET) was examined for medical assistant
      students (n = 448). Differences in domain-specific vocational knowledge were
      predicted by crystallized and fluid intelligence in the course of VET. A multiple
      matrix design with 3 year-specific booklets was used for the vocational knowledge
      tests of the medical assistants. The unique and joint contributions of the
      predictors were investigated with structural equation modeling. Crystallized
      intelligence emerged as the strongest predictor of vocational knowledge at every
      stage of VET, while fluid intelligence only showed weak effects. The present
      results support the knowledge-is-power hypothesis, even in a broad and more
      naturalistic setting. This emphasizes the relevance of general knowledge for
      occupations, such as medical assistants, which are more focused on learning hands
      on skills than the acquisition of academic knowledge.

PMID- 29449820
TI  - Headache and Alexithymia in Children and Adolescents: What Is the Connection?
AB  - Background: Headache is one of the most common complaints in children and
      adolescents and comorbidity rates are very high and the major associated diseases
      are depression, anxiety, atopic disorders, sleep, and behavioral disorders. In
      recent years, it has been highlighted that difficulties regulating emotions such
      as alexithymia have also been associated with diagnosis of somatization. Methods:
      We carried out a mini review analyzing the relation between alexithymia and
      primary headache (e.g., migraine and tension type headache) in children and
      adolescents by synthesizing the relevant studies in the literature on PubMed,
      PsycINFO, and Google Scholar. Search terms were "alexithymia" combined with the
      "primary headache," "migraine," "tension type headache," "children," and
      "adolescents." Results: All analyzed studies found higher levels of alexithymia
      in children and adolescents with headache than control groups but there are
      different opinions about the relationship between headache and alexithymia. For
      example, some studies suggest that the association between headache and
      alexithymia in children may be due to an incomplete development of emotive
      competency or a general immature cognitive development, instead other studies
      found a correlation between headache symptoms, insecure attachment, and
      alexithymia. There seems to be also differences between children with migraine
      compared to those with tension type headache (TTH). Conclusion: There are some
      studies on adults suffering from headache or migraine and alexithymia, but there
      is only a moderate amount of research on pediatric age with different opinions
      and theories about this relationship. Further studies on children and adolescents
      are necessary to effectively understand this relationship and to help children to
      reduce headache and improve emotional consciousness.

PMID- 29449816
TI  - Economic and Health Predictors of National Postpartum Depression Prevalence: A
      Systematic Review, Meta-analysis, and Meta-Regression of 291 Studies from 56
      Countries.
AB  - Background: Postpartum depression (PPD) poses a major global public health
      challenge. PPD is the most common complication associated with childbirth and
      exerts harmful effects on children. Although hundreds of PPD studies have been
      published, we lack accurate global or national PPD prevalence estimates and have
      no clear account of why PPD appears to vary so dramatically between nations.
      Accordingly, we conducted a meta-analysis to estimate the global and national
      prevalence of PPD and a meta-regression to identify economic, health, social, or
      policy factors associated with national PPD prevalence. Methods: We conducted a
      systematic review of all papers reporting PPD prevalence using the Edinburgh
      Postnatal Depression Scale. PPD prevalence and methods were extracted from each
      study. Random effects meta-analysis was used to estimate global and national PPD
      prevalence. To test for country level predictors, we drew on data from UNICEF,
      WHO, and the World Bank. Random effects meta-regression was used to test national
      predictors of PPD prevalence. Findings: 291 studies of 296284 women from 56
      countries were identified. The global pooled prevalence of PPD was 17.7% (95%
      confidence interval: 16.6-18.8%), with significant heterogeneity across nations
      (Q = 16,823, p = 0.000, I2 = 98%), ranging from 3% (2-5%) in Singapore to 38% (35
      41%) in Chile. Nations with significantly higher rates of income inequality (R2 =
      41%), maternal mortality (R2 = 19%), infant mortality (R2 = 16%), or women of
      childbearing age working >=40 h a week (R2 = 31%) have higher rates of PPD.
      Together, these factors explain 73% of the national variation in PPD prevalence.
      Interpretation: The global prevalence of PPD is greater than previously thought
      and varies dramatically by nation. Disparities in wealth inequality and maternal
      child-health factors explain much of the national variation in PPD prevalence.

PMID- 29449821
TI  - Intentional Forgetting in Organizations: The Importance of Eliminating Retrieval
      Cues for Implementing New Routines.
AB  - To cope with the already large, and ever increasing, amount of information stored
      in organizational memory, "forgetting," as an important human memory process,
      might be transferred to the organizational context. Especially in intentionally
      planned change processes (e.g., change management), forgetting is an important
      precondition to impede the recall of obsolete routines and adapt to new strategic
      objectives accompanied by new organizational routines. We first comprehensively
      review the literature on the need for organizational forgetting and particularly
      on accidental vs. intentional forgetting. We discuss the current state of the art
      of theory and empirical evidence on forgetting from cognitive psychology in order
      to infer mechanisms applicable to the organizational context. In this respect, we
      emphasize retrieval theories and the relevance of retrieval cues important for
      forgetting. Subsequently, we transfer the empirical evidence that the elimination
      of retrieval cues leads to faster forgetting to the forgetting of organizational
      routines, as routines are part of organizational memory. We then propose a
      classification of cues (context, sensory, business process-related cues) that are
      relevant in the forgetting of routines, and discuss a meta-cue called the
      "situational strength" cue, which is relevant if cues of an old and a new routine
      are present simultaneously. Based on the classification as business process
      related cues (information, team, task, object cues), we propose mechanisms to
      accelerate forgetting by eliminating specific cues based on the empirical and
      theoretical state of the art. We conclude that in intentional organizational
      change processes, the elimination of cues to accelerate forgetting should be used
      in change management practices.

PMID- 29449822
TI  - Attachment Patterns and Complex Trauma in a Sample of Adults Diagnosed with
      Gender Dysphoria.
AB  - The current study investigated attachment representations and complex trauma in a
      sample of gender dysphoric adults. Although it has been proven that the
      psychological wellbeing of gender diverse persons is largely mediated by family
      acceptance and support, research on their relationships with parental figures is
      scarce. A total of 95 adults took part in the study. The attachment distribution
      was as follows: 27% secure, 27% insecure and 46% disorganized. Regarding early
      traumas, 56% experienced four or more traumatic forms. Further, gender dysphoric
      adults showed significantly higher levels of attachment disorganization and
      polyvictimisation, relative to controls. Comparisons of subgroups, defined by
      natal gender, showed that trans women, compared to control males, had more
      involving and physically and psychologically abusive fathers, and were more often
      separated from their mothers; trans men, relative to female controls, had more
      involving mothers and were more frequently separated from and neglected by their
      fathers. The research has several implications for treatment, clinical health
      psychology, family support and education.

PMID- 29449823
TI  - Age Differences in Age Perceptions and Developmental Transitions.
AB  - Is 50 considered "old"? When do we stop being considered "young"? If individuals
      could choose to be any age, what would it be? In a sample of 502,548 internet
      respondents ranging in age from 10 to 89, we examined age differences in aging
      perceptions (e.g., how old do you feel?) and estimates of the timing of
      developmental transitions (e.g., when does someone become an older adult?). We
      found that older adults reported older perceptions of aging (e.g., choosing to be
      older, feeling older, being perceived as older), but that these perceptions were
      increasingly younger than their current age. The age to which individuals hope to
      live dramatically increased after age 40. We also found that older adults placed
      the age at which developmental transitions occurred later in the life course.
      This latter effect was stronger for transitions involving middle-age and older
      adulthood compared to transitions involving young adulthood. The current study
      constitutes the largest study to date of age differences in age perceptions and
      developmental timing estimates and yielded novel insights into how the aging
      process may affect judgments about the self and others.

PMID- 29449824
TI  - Reduced Self-Control after 3 Months of Imprisonment; A Pilot Study.
AB  - Background: Prison can be characterized as an impoverished environment
      encouraging a sedentary lifestyle with limited autonomy and social interaction,
      which may negatively affect self-control and executive function. Here, we aim to
      study the effects of imprisonment on self-control and executive functions, and we
      report the change in neuropsychological outcome after 3 months of imprisonment.
      Materials and Methods: Participants were 37 male inmates in a remand prison in
      Amsterdam, Netherlands, who completed six tests of a computerized
      neuropsychological test battery (the Cambridge Automated Neuropsychological Test
      Battery) in the first week of arrival. Participants were retested after 3 months
      of imprisonment. Change in performance was tested using the Wilcoxon Signed-Rank
      test. Results: After 3 months of imprisonment, risk taking significantly
      increased (measured as an increase in the proportion of available points used for
      betting) and attention significantly deteriorated (measured as increased
      variability in reaction times on a sustained attention task), with large to
      medium effect sizes. In contrast, planning significantly improved (measured with
      a task analog to the Tower of London) with a medium effect size. Discussion: Our
      study suggests that 3 months of imprisonment in an impoverished environment may
      lead to reduced self-control, measured as increased risk taking and reduced
      attentional performance. This is a significant and societally relevant finding,
      as released prisoners may be less capable of living a lawful life than they were
      prior to their imprisonment, and may be more prone to impulsive risk-taking
      behavior. In other words, the impoverished environment may contribute to an
      enhanced risk of reoffending.

PMID- 29449826
TI  - A Critical Examination of Subgroup Analyses: The National Acute Spinal Cord
      Injury Studies and Beyond.
AB  - The use of high-dose methylprednisolone for acute spinal cord injury continues to
      be a topic of debate. This controversy largely stems from fundamental issues in
      statistical interpretation of trial data, most notably subgroup analyses. The
      purpose of this review is to discuss important examples of improper subgroup
      analysis and encourage better practices in future research.

PMID- 29449825
TI  - Technologies for Advanced Gait and Balance Assessments in People with Multiple
      Sclerosis.
AB  - Subtle gait and balance dysfunction is a precursor to loss of mobility in
      multiple sclerosis (MS). Biomechanical assessments using advanced gait and
      balance analysis technologies can identify these subtle changes and could be used
      to predict mobility loss early in the disease. This update critically evaluates
      advanced gait and balance analysis technologies and their applicability to
      identifying early lower limb dysfunction in people with MS. Non-wearable (motion
      capture systems, force platforms, and sensor-embedded walkways) and wearable
      (pressure and inertial sensors) biomechanical analysis systems have been
      developed to provide quantitative gait and balance assessments. Non-wearable
      systems are highly accurate, reliable and provide detailed outcomes, but require
      cumbersome and expensive equipment. Wearable systems provide less detail but can
      be used in community settings and can provide real-time feedback to patients and
      clinicians. Biomechanical analysis using advanced gait and balance analysis
      technologies can identify changes in gait and balance in early MS and
      consequently have the potential to significantly improve monitoring of mobility
      changes in MS.

PMID- 29449827
TI  - Sun Exposure across the Life Course Significantly Modulates Early Multiple
      Sclerosis Clinical Course.
AB  - Background: Low vitamin D and/or sun exposure have been associated with increased
      risk of multiple sclerosis (MS) onset. However, comparatively, few studies have
      prospectively examined associations between these factors and clinical course.
      Objectives: To evaluate the association of sun exposure parameters and vitamin D
      levels with conversion to MS and relapse risk in a prospectively monitored cohort
      of 145 participants followed after a first demyelinating event up to 5-year
      review (AusLong Study). Methods: Sun exposure prior to and after onset measured
      by annual questionnaire; ultraviolet radiation (UVR) "load" estimated by location
      of residence over the life course and ambient UVR levels. Serum 25-hydroxyvitamin
      D [25(OH)D] concentrations measured at baseline, 2/3-year, and 5-year review. MS
      conversion and relapse assessed by neurologist assessment and medical record
      review. Results: Over two-thirds (69%) of those followed to 5-year review
      (100/145) converted to MS, with a total of 252 relapses. Higher pre-MS onset sun
      exposure was associated with reduced risk of MS conversion, with internal
      consistency between measures and dose-response relationships. Analogous
      associations were also seen with risk of relapse, albeit less strong. No
      consistent associations were observed between postonset sun exposure and clinical
      course, however. Notably, those who increased their sun exposure during follow-up
      had significantly reduced hazards of MS conversion and relapse. Serum 25(OH)D
      levels and vitamin D supplementation were not associated with conversion to MS or
      relapse hazard. Conclusion: We found that preonset sun exposure was protective
      against subsequent conversion to MS and relapses. While consistent associations
      between postonset sun exposure or serum 25(OH)D level and clinical course were
      not evident, possibly masked by behavior change, those participants who markedly
      increased their sun exposure demonstrated a reduced MS conversion and relapse
      hazard, suggesting beneficial effects of sun exposure on clinical course.

PMID- 29449829
TI  - Effects of Vitamin D Deficiency on Incidence Risk of Gestational Diabetes
      Mellitus: A Systematic Review and Meta-analysis.
AB  - Introduction: Proper nutrition is important for overall health, and it reduces
      healthcare costs associated with malnutrition. Many studies have investigated
      vitamin D deficiency and its role in gestational diabetes and controversial data
      have reported. A comprehensive consideration of articles in this field provides
      the possibility of a general study of this relationship. This meta-analysis is an
      evaluation of the relationship between vitamin D deficiency and gestational
      diabetes. Material and methods: Different databases (such as PubMed, Science
      Information Institute, EmBase, Scopus, and the Cochrane Library) were searched
      for studies and eligible English articles published before February 2017 that
      have reported the risk of gestational diabetes in relation to vitamin D
      deficiency. This relationship was measured using odds ratios (ORs) with a
      confidence interval (CI) of 95%. The influence of each study was measured through
      sensitivity analysis. Funnel plots, Egger regression tests, and the Begg-Mazumdar
      correlation test were used to determine bias or publication bias. STATA (version
      11.2) was used for all analyses. Results: Twenty-six studies were selected as
      eligible for this research and included in the final analysis. In general,
      vitamin D deficiency among mothers may be related to an increased risk of
      gestational diabetes (OR = 1.18; 95% CI, 1.01-1.35; p < 0.001). The serum level
      of 25(OH)D is less meaningful in people with gestational diabetes than in those
      who have normal glucose tolerance. Subgroup analysis showed that the results
      concerning this association may vary with study design but do not change with
      country of origin. Conclusion: Some evidence has shown that vitamin D deficiency
      may increase the risk of gestational diabetes.

PMID- 29449828
TI  - Understanding Spreading Depression from Headache to Sudden Unexpected Death.
AB  - Spreading depression (SD) is a neurophysiological phenomenon characterized by
      abrupt changes in intracellular ion gradients and sustained depolarization of
      neurons. It leads to loss of electrical activity, changes in the synaptic
      architecture, and an altered vascular response. Although SD is often described as
      a unique phenomenon with homogeneous characteristics, it may be strongly affected
      by the particular triggering event and by genetic background. Furthermore, SD may
      contribute differently to the pathogenesis of widely heterogeneous clinical
      conditions. Indeed, clinical disorders related to SD vary in their presentation
      and severity, ranging from benign headache conditions (migraine syndromes) to
      severely disabling events, such as cerebral ischemia, or even death in people
      with epilepsy. Although the characteristics and mechanisms of SD have been
      dissected using a variety of approaches, ranging from cells to human models, this
      phenomenon remains only partially understood because of its complexity and the
      difficulty of obtaining direct experimental data. Currently, clinical monitoring
      of SD is limited to patients who require neurosurgical interventions and the
      placement of subdural electrode strips. Significantly, SD events recorded in
      humans display electrophysiological features that are essentially the same as
      those observed in animal models. Further research using existing and new
      experimental models of SD may allow a better understanding of its core
      mechanisms, and of their differences in different clinical conditions, fostering
      opportunities to identify and develop targeted therapies for SD-related disorders
      and their worst consequences.

PMID- 29449830
TI  - Screening for PPAR Non-Agonist Ligands Followed by Characterization of a Hit, AM
      879, with Additional No-Adipogenic and cdk5-Mediated Phosphorylation Inhibition
      Properties.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of a
      nuclear receptor superfamily and acts as a ligand-dependent transcription factor,
      playing key roles in maintenance of adipose tissue and in regulation of glucose
      and lipid homeostasis. This receptor is the target of thiazolidinediones, a class
      of antidiabetic drugs, which improve insulin sensitization and regulate glycemia
      in type 2 diabetes. Despite the beneficial effects of drugs, such as
      rosiglitazone and pioglitazone, their use is associated with several side
      effects, including weight gain, heart failure, and liver disease, since these
      drugs induce full activation of the receptor. By contrast, a promising activation
      independent mechanism that involves the inhibition of cyclin-dependent kinase 5
      (CDK5)-mediated PPARgamma phosphorylation has been related to the insulin
      sensitizing effects induced by these drugs. Thus, we aimed to identify novel
      PPARgamma ligands that do not possess agonist properties by conducting a mini
      trial with 80 compounds using the sequential steps of thermal shift assay, 8
      anilino-1-naphthalenesulfonic acid fluorescence quenching, and a cell-based
      transactivation assay. We identified two non-agonist PPARgamma ligands, AM-879
      and P11, and one partial-agonist, R32. Using fluorescence anisotropy, we show
      that AM-879 does not dissociate the NCOR corepressor in vitro, and it has only a
      small effect on TRAP coactivator recruitment. In cells, AM-879 could not induce
      adipocyte differentiation or positively regulate the expression of genes
      associated with adipogenesis. In addition, AM-879 inhibited CDK5-mediated
      phosphorylation of PPARgamma in vitro. Taken together, these findings supported
      an interaction between AM-879 and PPARgamma; this interaction was identified by
      the analysis of the crystal structure of the PPARgamma:AM-879 complex and
      evidenced by AM-879's mechanism of action as a putative PPARgamma non-agonist
      with antidiabetic properties. Moreover, we present an optimized assay pipeline
      capable of detecting ligands that physically bind to PPARgamma but do not cause
      its activation as a new strategy to identify ligands for this nuclear receptor.

PMID- 29449831
TI  - Aspergillus terreus Inhibits Growth and Induces Morphological Abnormalities in
      Pythium aphanidermatum and Suppresses Pythium-Induced Damping-Off of Cucumber.
AB  - The study investigated the efficacy of two isolates of Aspergillus terreus (65P
      and 9F) on the growth, morphology and pathogenicity of Pythium aphanidermatum on
      cucumber. In vitro tests showed that the two isolates inhibited the growth of P.
      aphanidermatum in culture. Investigating P. aphanidermatum hyphae close to the
      inhibition zone showed that the hyphae showed abnormal growth and loss of
      internal content. Treating P. aphanidermatum with the culture filtrate (CF) of A.
      terreus resulted in significant rise in cellular leakage of P. aphanidermatum
      mycelium. Testing glucanase enzyme activity by both A. terreus isolates showed a
      significant increase in glucanase activity. This suggests that the cell walls of
      Pythium, which consist of glucan, are affected by the glucanase enzyme produced
      by A. terreus. In addition, Aspergillus isolates produced siderephore, which is
      suggested to be involved in inhibition of Pythium growth. Also, the CFs of 65P
      and 9F isolates significantly reduced spore production by P. aphanidermatum
      compared to the control (P < 0.05). In bioassay tests, the two isolates of A.
      terreus increased the survival rate of cucumber seedlings from 10 to 20% in the
      control seedlings treated with P. aphanidermatum to 38-39% when the biocontrol
      agents were used. No disease symptoms were observed on cucumber seedlings only
      treated with the isolates 65P and 9F of A. terreus. In addition, the A. terreus
      isolates did not have any negative effects on the growth of cucumber seedlings.
      This study shows that isolates of A. terreus can help suppress Pythium-induced
      damping-off of cucumber, which is suggested to be through the effect of A.
      terreus and its glucanase enzyme on P. aphanidermatum mycelium.

PMID- 29449832
TI  - Rhizosphere Competence and Biocontrol Effect of Pseudomonas sp. RU47 Independent
      from Plant Species and Soil Type at the Field Scale.
AB  - Biocontrol inoculants often show inconsistency in their efficacy at field scale
      and the reason for this remains often unclear. A high rhizosphere competence of
      inoculant strains is assumed to be a key factor for successful biocontrol effects
      as the biocontrol strain has to compete with the indigenous microbial community
      in the rhizosphere. It is known that many factors, among them plant species and
      soil type shape the rhizosphere microbial community composition. However,
      microbial community composition in the rhizosphere can also be influenced by the
      presence of a pathogen. We hypothesized that plant species, soil type, and a
      pathogen affect the rhizosphere competence of a biocontrol strain and its
      biocontrol effect against a soil-borne pathogen. To test the hypothesis, we used
      an experimental plot system with three soil types (diluvial sand, alluvial loam,
      loess loam) kept under similar agricultural management at the same field site for
      12 years. We investigate the rhizosphere competence of Pseudomonas sp. RU47 in
      two plant species (potato and lettuce) and its biocontrol effect against
      Rhizoctonia diseases. The colonization density of a rifampicin resistant mutant
      of RU47 in the rhizosphere of both crops was evaluated by plate counts. Bacterial
      community compositions were analyzed by denaturing gradient gel electrophoresis
      (DGGE) of 16S rRNA gene fragments amplified from total community DNA. The
      inoculant RU47 was able to colonize the rhizosphere of both model crops in a
      sufficient density and to reduce disease severity of black scurf on potato and
      bottom rot on lettuce in all three soils. DGGE indicated that RU47 affected the
      bacterial community composition stronger in the rhizosphere of lettuce than in
      the potato rhizosphere. In contrast, the effect of the pathogen Rhizoctonia
      solani on the bacterial community was much stronger in the rhizosphere of potato
      than in the lettuce rhizosphere. A significant effect of RU47 on the Pseudomonas
      specific gacA fingerprints of the rhizosphere was only observed in lettuce in
      alluvial soil. The soil type and plant species independent biocontrol effects of
      RU47 and its minor influence on the indigenous bacterial community composition
      might be important criteria for the registration and use of RU47 as biocontrol
      strain.

PMID- 29449833
TI  - Stem-Loop RNA Hairpins in Giant Viruses: Invading rRNA-Like Repeats and a
      Template Free RNA.
AB  - We examine the hypothesis that de novo template-free RNAs still form
      spontaneously, as they did at the origins of life, invade modern genomes,
      contribute new genetic material. Previously, analyses of RNA secondary structures
      suggested that some RNAs resembling ancestral (t)RNAs formed recently de novo,
      other parasitic sequences cluster with rRNAs. Here positive control analyses of
      additional RNA secondary structures confirm ancestral and de novo statuses of RNA
      grouped according to secondary structure. Viroids with branched stems resemble de
      novo RNAs, rod-shaped viroids resemble rRNA secondary structures, independently
      of GC contents. 5' UTR leading regions of West Nile and Dengue flavivirid viruses
      resemble de novo and rRNA structures, respectively. An RNA homologous with
      Megavirus, Dengue and West Nile genomes, copperhead snake microsatellites and
      levant cotton repeats, not templated by Mimivirus' genome, persists throughout
      Mimivirus' infection. Its secondary structure clusters with candidate de novo
      RNAs. The saltatory phyletic distribution and secondary structure of Mimivirus'
      peculiar RNA suggest occasional template-free polymerization of this sequence,
      rather than noncanonical transcriptions (swinger polymerization,
      posttranscriptional editing).

PMID- 29449834
TI  - Peptidoglycan Recognition Protein 3 Does Not Alter the Outcome of Pneumococcal
      Pneumonia in Mice.
AB  - Pneumococci frequently cause community-acquired pneumonia, a disease with high
      mortality rates, particularly in young children and in the elderly. Endogenous
      antimicrobial peptides and proteins such as PGLYRP3 may contribute to the
      progression and outcome of this disease. Since increasing antibiotic resistant
      strains occur all over the world, these endogenous antimicrobial molecules are
      interesting new targets for future therapies. In this study, the expression
      pattern of PGLYRP3 was analyzed in alveolar epithelial cells, alveolar
      macrophages and neutrophils. Additionally, the function of PGLYRP3 during
      Streptococcus pneumoniae-induced pneumonia was investigated in a murine
      pneumococcal pneumonia model using PGLYRP3KO mice. PGLYRP3 is expressed in all
      selected cell types but pneumococcus-dependent induction of PGLYRP3 was observed
      only in neutrophils and alveolar macrophages. Interestingly, there were no
      significant differences in the bacterial loads within the lungs, the blood or the
      spleens, in the cytokine response, the composition of immune cells and the
      histopathology between wild type and PGLYRP3KO mice. Finally, we could neither
      observe significant differences in the clinical symptoms nor in the overall
      survival. Collectively, PGLYRP3 seems to be dispensable for the antibacterial
      defense during pneumococcal pneumonia.

PMID- 29449835
TI  - ComX-Induced Exoproteases Degrade ComX in Bacillus subtilis PS-216.
AB  - Gram-positive bacteria use peptides as auto-inducing (AI) signals to regulate the
      production of extracellular enzymes (e.g., proteases). ComX is an AI peptide,
      mostly known for its role in the regulation of bacterial competence and
      surfactant production in Bacillus subtilis. These two traits are regulated
      accordingly to the bacterial population size, thus classifying ComX as a quorum
      sensing signal. ComX also indirectly regulates exoprotease production through the
      intermediate transcriptional regulator DegQ. We here use this peptide-based AI
      system (the ComQXPA system) as a model to address exoprotease regulation by ComX
      in biofilms. We also investigate the potential of ComX regulated proteases to
      degrade the ComX AI peptide. Results indicate that ComX indeed induces the
      expression of aprE, the gene for the major serine protease subtilisin, and
      stimulates overall exoprotease production in biofilms of B. subtilis PS-216 and
      several other B. subtilis soil isolates. We also provide evidence that these
      exoproteases can degrade ComX. The ComX biological activity decay is reduced in
      the spent media of floating biofilms with low proteolytic activity found in the
      comP and degQ mutants. ComX biological activity decay can be restored by the
      addition of subtilisin to such media. In contrast, inhibition of metalloproteases
      by EDTA reduces ComX biological activity decay. This suggests that both serine
      and metalloproteases, which are induced by ComX, are ultimately capable of
      degrading this signaling peptide. This work brings novel information on
      regulation of exoproteases in B. subtilis floating biofilms and reveals that
      these proteolytic enzymes degrade the AI signaling peptide ComX, which is also a
      major determinant of their expression in biofilms.

PMID- 29449836
TI  - Changes in Microbial Energy Metabolism Measured by Nanocalorimetry during Growth
      Phase Transitions.
AB  - Calorimetric measurements of the change in heat due to microbial metabolic
      activity convey information about the kinetics, as well as the thermodynamics, of
      all chemical reactions taking place in a cell. Calorimetric measurements of heat
      production made on bacterial cultures have recorded the energy yields of all co
      occurring microbial metabolic reactions, but this is a complex, composite signal
      that is difficult to interpret. Here we show that nanocalorimetry can be used in
      combination with enumeration of viable cell counts, oxygen consumption rates,
      cellular protein content, and thermodynamic calculations to assess catabolic
      rates of an isolate of Shewanella oneidensis MR-1 and infer what fraction of the
      chemical energy is assimilated by the culture into biomass and what fraction is
      dissipated in the form of heat under different limiting conditions. In
      particular, our results demonstrate that catabolic rates are not necessarily
      coupled to rates of cell division, but rather, to physiological rearrangements of
      S. oneidensis MR-1 upon growth phase transitions. In addition, we conclude that
      the heat released by growing microorganisms can be measured in order to
      understand the physiochemical nature of the energy transformation and dissipation
      associated with microbial metabolic activity in conditions approaching those
      found in natural systems.

PMID- 29449837
TI  - Cyclic-di-GMP and oprF Are Involved in the Response of Pseudomonas aeruginosa to
      Substrate Material Stiffness during Attachment on Polydimethylsiloxane (PDMS).
AB  - Recently, we reported that the stiffness of poly(dimethylsiloxane) (PDMS) affects
      the attachment of Pseudomonas aeruginosa, and the morphology and antibiotic
      susceptibility of attached cells. To further understand how P. aeruginosa
      responses to material stiffness during attachment, the wild-type P. aeruginosa
      PAO1 and several isogenic mutants were characterized for their attachment on soft
      and stiff PDMS. Compared to the wild-type strain, mutation of the oprF gene
      abolished the differences in attachment, growth, and size of attached cells
      between soft and stiff PDMS surfaces. These defects were rescued by genetic
      complementation of oprF. We also found that the wild-type P. aeruginosa PAO1
      cells attached on soft (40:1) PDMS have higher level of intracellular cyclic
      dimeric guanosine monophosphate (c-di-GMP), a key regulator of biofilm formation,
      compared to those on stiff (5:1) PDMS surfaces. Consistently, the mutants of fleQ
      and wspF, which have similar high-level c-di-GMP as the oprF mutant, exhibited
      defects in response to PDMS stiffness during attachment. Collectively, the
      results from this study suggest that P. aeruginosa can sense the stiffness of
      substrate material during attachment and respond to such mechanical cues by
      adjusting c-di-GMP level and thus the following biofilm formation. Further
      understanding of the related genes and pathways will provide new insights into
      bacterial mechanosensing and help develop better antifouling materials.

PMID- 29449838
TI  - The Divergence in Bacterial Components Associated with Bactrocera dorsalis across
      Developmental Stages.
AB  - Eco-evolutionary dynamics of microbiotas at the macroscale level are largely
      driven by ecological variables. The diet and living environment of the oriental
      fruit fly, Bactrocera dorsalis, diversify during development, providing a natural
      system to explore convergence, divergence, and repeatability in patterns of
      microbiota dynamics as a function of the host diet, phylogeny, and environment.
      Here, we characterized the microbiotas of 47 B. dorsalis individuals from three
      distinct populations by 16S rRNA amplicon sequencing. A significant deviation was
      found within the larvae, pupae, and adults of each population. Pupae were
      characterized by an increased bacterial taxonomic and functional diversity.
      Principal components analysis showed that the microbiotas of larvae, pupae, and
      adults clearly separated into three clusters. Acetobacteraceae, Lactobacillaceae,
      and Enterobacteriaceae were the predominant families in larval and adult samples,
      and PICRUSt analysis indicated that phosphoglycerate mutases and transketolases
      were significantly enriched in larvae, while phosphoglycerate mutases,
      transketolases, and proteases were significantly enriched in adults, which may
      support the digestive function of the microbiotas in larvae and adults. The
      abundances of Intrasporangiaceae, Dermabacteraceae (mainly Brachybacterium) and
      Brevibacteriaceae (mainly Brevibacterium) were significantly higher in pupae, and
      the antibiotic transport system ATP-binding protein and antibiotic transport
      system permease protein pathways were significantly enriched there as well,
      indicating the defensive function of microbiotas in pupae. Overall, differences
      in the microbiotas of the larvae, pupae, and adults are likely to contribute to
      differences in nutrient assimilation and living environments.

PMID- 29449839
TI  - Long-term Maintenance of CD4 T Cell Memory Responses to Malaria Antigens in
      Malian Children Coinfected with Schistosoma haematobium.
AB  - Polyparasitism is common in the developing world. We have previously demonstrated
      that schistosomiasis-positive (SP) Malian children, aged 4-8 years, are protected
      from malaria compared to matched schistosomiasis-negative (SN) children. The
      effect of concomitant schistosomiasis upon acquisition of T cell memory is
      unknown. We examined antigen-specific T cell frequencies in 48 Malian children
      aged 4-14 to a pool of malaria blood stage antigens, and a pool of schistosomal
      antigens, at a time point during a malaria episode and at a convalescent time
      point ~6 months later, following cessation of malaria transmission. CD4+ T cell
      derived memory responses, defined as one or more significant cytokine (IFN-gamma,
      TNF-alpha, IL-2, and/or IL-17A) responses, was measured to schistoma antigens in
      18/23 SP children at one or both time points, compared to 4/23 SN children (P <
      0.0001). At the time of malaria infection, 12/24 SN children and 15/23 SP
      children (P = 0.29) stimulated with malaria antigens demonstrated memory recall
      as defined by CD4-derived cytokine production. This compares to 7/23 SN children
      and 16/23 SP children (P = 0.009) at the convalescent timepoint. 46.2% of
      cytokine-producing CD4+ T cells expressed a single cytokine after stimulation
      with malaria antigen during the malaria episode. This fell to 40.9% at follow-up
      with a compensatory rise of multifunctional cytokine secretion over time, a
      phenomenon consistent with memory maturation. The majority (53.2-59.5%) of
      responses derived from CD45RA-CD62L- effector memory T cells with little
      variation in the phenotype depending upon the time point or the study cohort. We
      conclude that detectable T cell memory responses can be measured against both
      malaria and schistosoma antigens and that the presence of Schistosoma haematobium
      may be associated with long-term maintenance of T memory to malaria.

PMID- 29449840
TI  - c-Abl-TWIST1 Epigenetically Dysregulate Inflammatory Responses during
      Mycobacterial Infection by Co-Regulating Bone Morphogenesis Protein and miR27a.
AB  - Mycobacteria propelled modulation of host responses is of considerable interest
      in the face of emerging drug resistance. Although it is known that Abl tyrosine
      kinases affect entry and persistence of mycobacteria, mechanisms that couple c
      Abl to proximal signaling pathways during immunity are poorly understood. Loss-of
      function of c-Abl through Imatinib, in a mouse model of tuberculosis or RNA
      interference, identified bone morphogenesis protein (BMP) signaling as its
      cellular target. We demonstrate that c-Abl promotes mycobacterial survival
      through epigenetic modification brought about by KAT5-TWIST1 at Bmp loci. c-Abl
      BMP signaling deregulated iNOS, aggravating the inflammatory balance.
      Interestingly, BMP signaling was observed to have far-reaching effects on host
      immunity, as it attenuated TLR3 pathway by engaging miR27a. Significantly, these
      events were largely mediated via WhiB3 and DosR/S/T but not SecA signaling
      pathway of mycobacteria. Our findings suggest molecular mechanisms of host
      pathways hijacked by mycobacteria and expand our understanding of c-Abl
      inhibitors in potentiating innate immune responses.

PMID- 29449842
TI  - Pan-Influenza A Protection by Prime-Boost Vaccination with Cold-Adapted Live
      Attenuated Influenza Vaccine in a Mouse Model.
AB  - Influenza virus infections continually pose a major public health threat with
      seasonal epidemics and sporadic pandemics worldwide. While currently licensed
      influenza vaccines provide only strain-specific protection, antigenic drift and
      shift occasionally render the viruses resistant to the host immune responses,
      which highlight the need for a vaccine that provides broad protection against
      multiple subtypes. In this study, we suggest a vaccination strategy using cold
      adapted, live attenuated influenza vaccines (CAIVs) to provide a broad, potent,
      and safe cross-protection covering antigenically distinct hemagglutinin (HA)
      groups 1 and 2 influenza viruses. Using a mouse model, we tested different prime
      boost combinations of CAIVs for their ability to induce humoral and T-cell
      responses, and protective efficacy against H1 and H5 (HA group 1) as well as H3
      and H7 (HA group 2) influenza viruses. Notably, even in the absence of antibody
      mediated neutralizing activity or HA inhibitory activity in vitro, CAIVs provided
      a potent protection against heterologous and heterosubtypic lethal challenges in
      vivo. Heterologous combination of prime (H1)-boost (H5) vaccine strains showed
      the most potent cross-protection efficacy. In vivo depletion experiments
      demonstrated not only that T cells and natural killer cells contributed to the
      cross-protection, but also the involvement of antibody-dependent mechanisms for
      the cross-protection. Vaccination-induced antibodies did not enhance the
      infectivity of heterologous viruses, and prime vaccination did not interfere with
      neutralizing antibody generation by the boost vaccination, allaying vaccine
      safety concerns associated with heterogeneity between the vaccines and challenge
      strains. Our data show that CAIV-based strategy can serve as a simple but
      powerful option for developing a "truly" universal influenza vaccine providing
      pan-influenza A protection, which has not been achieved yet by other vaccine
      strategies. The promising results of potency, breadth, and safety demonstrated in
      the mouse model support further studies in higher animal models for clinical
      relevance.

PMID- 29449841
TI  - Langerhans Cells: Sensing the Environment in Health and Disease.
AB  - In the last few decades, our understanding of Langerhans cells (LCs) has
      drastically changed based on novel findings regarding the developmental origin
      and biological functions of these epidermis-specific resident immune cells. It
      has become clear that LCs not only exert pivotal roles in immune surveillance and
      homeostasis but also impact on pathology by either inducing tolerance or
      mediating inflammation. Their unique capabilities to self-renew within the
      epidermis, while also being able to migrate to lymph nodes in order to present
      antigen, place LCs in a key position to sample the local environment and decide
      on the appropriate cutaneous immune response. Exciting new data distinguishing
      LCs from Langerin+ dermal dendritic cells (DCs) on a functional and ontogenic
      level reveal crucial roles for LCs in trauma and various skin pathologies, which
      will be thoroughly discussed here. However, despite rapid progress in the field,
      the exact role of LCs during immune responses has not been completely elucidated.
      This review focuses on what mouse models that have been developed in order to
      enable the study of murine LCs and other Langerin-expressing DCs have taught us
      about LC development and function.

PMID- 29449843
TI  - Insights into the Structural Basis of Antibody Affinity Maturation from Next
      Generation Sequencing.
AB  - Affinity maturation is the process whereby the immune system generates antibodies
      of higher affinities during a response to antigen. It is unique in being the only
      evolutionary mechanism known to operate on a molecule in an organism's own body.
      Deciphering the structural mechanisms through which somatic mutations in antibody
      genes increase affinity is critical to understanding the evolution of immune
      repertoires. Next-generation sequencing (NGS) has allowed the reconstruction of
      antibody clonal lineages in response to viral pathogens, such as HIV-1, which was
      not possible in earlier studies of affinity maturation. Crystal structures of
      antibodies from these lineages bound to their target antigens have revealed, at
      the atomic level, how antibodies evolve to penetrate the glycan shield of
      envelope glycoproteins, and how viruses in turn evolve to escape neutralization.
      Collectively, structural studies of affinity maturation have shown that increased
      antibody affinity can arise from any one or any combination of multiple diverse
      mechanisms, including improved shape complementarity at the interface with
      antigen, increased buried surface area upon complex formation, additional
      interfacial polar or hydrophobic interactions, and preorganization or
      rigidification of the antigen-binding site.

PMID- 29449844
TI  - Commentary: Maintenance of CD8+ T Memory Lymphocytes in the Spleen but Not in the
      Bone Marrow Is Dependent on Proliferation.

PMID- 29449846
TI  - Pemphigus-A Disease of Desmosome Dysfunction Caused by Multiple Mechanisms.
AB  - Pemphigus is a severe autoimmune-blistering disease of the skin and mucous
      membranes caused by autoantibodies reducing desmosomal adhesion between
      epithelial cells. Autoantibodies against the desmosomal cadherins desmogleins
      (Dsgs) 1 and 3 as well as desmocollin 3 were shown to be pathogenic, whereas the
      role of other antibodies is unclear. Dsg3 interactions can be directly reduced by
      specific autoantibodies. Autoantibodies also alter the activity of signaling
      pathways, some of which regulate cell cohesion under baseline conditions and
      alter the turnover of desmosomal components. These pathways include Ca2+,
      p38MAPK, PKC, Src, EGFR/Erk, and several others. In this review, we delineate the
      mechanisms relevant for pemphigus pathogenesis based on the histology and the
      ultrastructure of patients' lesions. We then dissect the mechanisms which can
      explain the ultrastructural hallmarks detectable in pemphigus patient skin.
      Finally, we reevaluate the concept that the spectrum of mechanisms, which induce
      desmosome dysfunction upon binding of pemphigus autoantibodies, finally defines
      the clinical phenotype.

PMID- 29449845
TI  - Regulation of C-Type Lectin Receptor-Mediated Antifungal Immunity.
AB  - Of all the pathogen recognition receptor families, C-type lectin receptor (CLR)
      induced intracellular signal cascades are indispensable for the initiation and
      regulation of antifungal immunity. Ongoing experiments over the last decade have
      elicited diverse CLR functions and novel regulatory mechanisms of CLR-mediated
      signaling pathways. In this review, we highlight novel insights in antifungal
      innate and adaptive-protective immunity mediated by CLRs and discuss the
      potential therapeutic strategies against fungal infection based on targeting the
      mediators in the host immune system.

PMID- 29449847
TI  - Potential Epigenetic Regulation in the Germinal Center Reaction of Lymphoid
      Tissues in HIV/SIV Infection.
AB  - The production of high-affinity and broadly neutralizing antibodies plays a key
      role in the defense against pathogens. These antibody responses require effective
      germinal center (GC) reaction within anatomical niches of GCs, where follicular
      helper T (Tfh) cells provide cognate help to B cells for T cell-dependent
      antibody responses. Emerging evidences indicate that GC reaction in normal state
      and perhaps establishment of latent Tfh cell reservoir in HIV/SIV infection are
      tightly regulated by epigenetic histone modifications, which are responsible for
      activating or silencing chromatin. A better understanding of the mechanisms
      behind GC responses at cellular and molecular levels thus provides necessary
      knowledge for vaccination and immunotherapy. In this review, we discussed the
      epigenetic regulation of GC responses, especially for GC B and Tfh cell under
      normal state or HIV/SIV infection.

PMID- 29449848
TI  - A New Suite of Plasmid Vectors for Fluorescence-Based Imaging of Root Colonizing
      Pseudomonads.
AB  - In the terrestrial ecosystem, plant-microbe symbiotic associations are
      ecologically and economically important processes. To better understand these
      associations at structural and functional levels, different molecular and
      biochemical tools are applied. In this study, we have constructed a suite of
      vectors that incorporates several new elements into the rhizosphere stable, broad
      host vector pME6031. The new vectors are useful for studies requiring multi-color
      tagging and visualization of plant-associated, Gram-negative bacterial strains
      such as Pseudomonas plant growth promotion and biocontrol strains. A number of
      genetic elements, including constitutive promoters and signal peptides that
      target secretion to the periplasm, have been evaluated. Several next generation
      fluorescent proteins, namely mTurquoise2, mNeonGreen, mRuby2, DsRed-Express2 and
      E2-Crimson have been incorporated into the vectors for whole cell labeling or
      protein tagging. Secretion of mTurquoise2 and mNeonGreen into the periplasm of
      Pseudomonas fluorescens SBW25 has also been demonstrated, providing a vehicle for
      tagging proteins in the periplasmic compartment. A higher copy number version of
      select plasmids has been produced by introduction of a previously described repA
      mutation, affording an increase in protein expression levels. The utility of
      these plasmids for fluorescence-based imaging is demonstrated by root
      colonization of Solanum lycopersicum seedlings by P. fluorescens SBW25 in a
      hydroponic growth system. The plasmids are stably maintained during root
      colonization in the absence of selective pressure for more than 2 weeks.

PMID- 29449849
TI  - Comprehensive Cloning of Prunus mume Dormancy Associated MADS-Box Genes and Their
      Response in Flower Bud Development and Dormancy.
AB  - Dormancy Associated MADS-box genes are SVP/MADs-box members and supposed to play
      crucial roles in plant dormancy of perennial species. In Prunus mume, PmDAM6 has
      been previously identified to induce plant dormancy. In the current study, six
      PmDAMs were cloned in P. mume and functionally analyzed in yeast and tobacco to
      detect the roles of the genes paralogous to PmDAM6. The expression patterns
      together with sequence similarities indicate that PmDAMs are divided into two sub
      clades within SVP group. Moreover, PmDAMs are verified to take part in the
      development of different plant organs, specifically the flower buds, in some
      intricate patterns. Furthermore, the PmDAM proteins are found to have special
      functions by forming corresponding protein complex during the development of
      flower bud and induction of dormancy. In particular, when PmDAM1 dominating in
      flower bud in the warm months, the protein complexes are consisted of PmDAM1
      itself or with PmDAM2. With the decrease temperatures in the following months,
      PmDAM6 was found to be highly expressed and gradually changed the complex
      structure to PmDAM6-protein complex due to strong binding tendencies with PmDAM1
      and PmDAM3. Finally, the homodimers of PmDAM6 prevailed to induce the dormancy.
      The results obtained in the current study highlight the functions of PmDAMs in
      the tissue development and dormancy, which provide available suggestions for
      further explorations of protein-complex functions in association with bud growth
      and dormancy.

PMID- 29449850
TI  - Irrigation and Nitrogen Regimes Promote the Use of Soil Water and Nitrate
      Nitrogen from Deep Soil Layers by Regulating Root Growth in Wheat.
AB  - Unreasonably high irrigation levels and excessive nitrogen (N) supplementation
      are common occurrences in the North China Plain that affect winter wheat
      production. Therefore, a 6-yr-long stationary field experiment was conducted to
      investigate the effects of irrigation and N regimes on root development and their
      relationship with soil water and N use in different soil layers. Compared to the
      non-irrigated treatment (W0), a single irrigation at jointing (W1) significantly
      increased yield by 3.6-45.6%. With increases in water (W2, a second irrigation at
      flowering), grain yield was significantly improved by 14.1-45.3% compared to the
      W1 treatments during the drier growing seasons (2010-2011, 2012-2013, and 2015
      2016). However, under sufficient pre-sowing soil moisture conditions, grain yield
      was not increased, and water use efficiency (WUE) decreased significantly in the
      W2 treatments during normal precipitation seasons (2011-2012, 2013-2014, and 2014
      2015). Irrigating the soil twice inhibited root growth into the deeper soil depth
      profiles and thus weakened the utilization of soil water and NO3-N from the deep
      soil layers. N applications increased yield by 19.1-64.5%, with a corresponding
      increase in WUE of 66.9-83.9% compared to the no-N treatment (N0). However, there
      was no further increase in grain yield and the WUE response when N rates exceeded
      240 and 180 kg N ha-1, respectively. A N application rate of 240 kg ha-1
      facilitated root growth in the deep soil layers, which was conducive to
      utilization of soil water and NO3-N and also in reducing the residual NO3-N.
      Correlation analysis indicated that the grain yield was significantly positively
      correlated with soil water storage (SWS) and nitrate nitrogen accumulation (SNA)
      prior to sowing. Therefore, N rates of 180-240 kg ha-1 with two irrigations can
      reduce the risk of yield loss that occurs due to reduced precipitation during the
      wheat growing seasons, while under better soil moisture conditions, a single
      irrigation at jointing was effective and more economical.

PMID- 29449851
TI  - Divergent N Deficiency-Dependent Senescence and Transcriptome Response in
      Developmentally Old and Young Brassica napus Leaves.
AB  - In the spring oilseed rape (OSR) cultivar 'Mozart' grown under optimal N supply
      (NO) or mild N deficiency (NL) the transcriptome changes associated with
      progressing age until early senescence in developmentally old lower canopy leaves
      (leaf #4) and younger higher canopy leaves (leaf #8) were investigated. Twelve
      weeks old NO and NL plants appeared phenotypically and transcriptomically
      identical, but thereafter distinct nutrition-dependent differences in gene
      expression patterns in lower and upper canopy leaves emerged. In NO leaves #4 of
      14-week-old compared to 13-week-old plants, ~600 genes were up- or downregulated,
      whereas in NL leaves #4 ~3000 genes were up- or downregulated. In contrast, in 15
      week-old compared to 13-week-old upper canopy leaves #8 more genes were up- or
      downregulated in optimally N-supplied plants (~2000 genes) than in N-depleted
      plants (~750 genes). This opposing effect of N depletion on gene regulation was
      even more prominent among photosynthesis-related genes (PSGs). Between week 13
      and 14 in leaves #4, 99 of 110 PSGs were downregulated in NL plants, but none in
      NO plants. In contrast, from weeks 13 to 16 in leaves #8 of NL plants only 11
      PSGs were downregulated in comparison to 66 PSGs in NO plants. Different effects
      of N depletion in lower versus upper canopy leaves were also apparent in
      upregulation of autophagy genes and NAC transcription factors. More than half of
      the regulated NAC and WRKY transcription factor, autophagy and protease genes
      were specifically regulated in NL leaves #4 or NO leaves #8 and thus may
      contribute to differences in senescence and nutrient mobilization in these
      leaves. We suggest that in N-deficient plants the upper leaves retain their N
      resources longer than in amply fertilized plants and remobilize them only after
      shedding of the lower leaves.

PMID- 29449852
TI  - Characterization of Sugar Contents and Sucrose Metabolizing Enzymes in Developing
      Leaves of Hevea brasiliensis.
AB  - Sucrose-metabolizing enzymes in plant leaves have hitherto been investigated
      mainly in temperate plants, and rarely conducted in tandem with gene expression
      and sugar analysis. Here, we investigated the sugar content, gene expression, and
      the activity of sucrose-metabolizing enzymes in the leaves of Hevea brasiliensis,
      a tropical tree widely cultivated for natural rubber. Sucrose, fructose and
      glucose were the major sugars detected in Hevea leaves at four developmental
      stages (I to IV), with starch and quebrachitol as minor saccharides. Fructose and
      glucose contents increased until stage III, but decreased strongly at stage IV
      (mature leaves). On the other hand, sucrose increased continuously throughout
      leaf development. Activities of all sucrose-cleaving enzymes decreased markedly
      at maturation, consistent with transcript decline for most of their encoding
      genes. Activity of sucrose phosphate synthase (SPS) was low in spite of its high
      transcript levels at maturation. Hence, the high sucrose content in mature leaves
      was not due to increased sucrose-synthesizing activity, but more to the decline
      in sucrose cleavage. Gene expression and activities of sucrose-metabolizing
      enzymes in Hevea leaves showed striking differences compared with other plants.
      Unlike in most other species where vacuolar invertase predominates in sucrose
      cleavage in developing leaves, cytoplasmic invertase and sucrose synthase
      (cleavage direction) also featured prominently in Hevea. Whereas SPS is normally
      responsible for sucrose synthesis in plant leaves, sucrose synthase (synthesis
      direction) was comparable or higher than that of SPS in Hevea leaves. Mature
      Hevea leaves had an unusually high sucrose:starch ratio of about 11, the highest
      reported to date in plants.

PMID- 29449853
TI  - Targeted Haplotype Comparisons between South African Wheat Cultivars Appear
      Predictive of Pre-harvest Sprouting Tolerance.
AB  - Pre-harvest sprouting (PHS) has been a serious production constraint for over two
      decades, especially in the summer rainfall wheat production regions of South
      Africa. It is a complex genetic trait controlled by multiple genes, which are
      significantly influenced by environmental conditions. This complicates the
      accurate prediction of a cultivar's stability in terms of PHS tolerance. A number
      of reports have documented the presence of major QTL on chromosomes 3A and 4A of
      modern bread wheat cultivars, which confer PHS tolerance. In this study, the SSR
      marker haplotype combination of chromosomes 3A and 4A of former and current South
      African cultivars were compared with the aim to select for improved PHS tolerance
      levels in future cultivars. A total of 101 wheat cultivars, including a
      susceptible cultivar and five international tolerant sources, were used in this
      study. These cultivars and donors were evaluated for their PHS tolerance by
      making use of a rain simulator. In addition, five seeds of each entry were
      planted out into seedling trays and leaf material harvested for DNA isolation. A
      modified CTAB extraction method was used before progressing to downstream PCR
      applications. Eight SSR markers targeted from the well-characterized 3A and 4A
      QTL regions associated with PHS tolerance, were used to conduct targeted
      haplotype analysis. Additionally, recently published KASP SNP markers, which
      identify the casual SNP mutations within the TaPHS1 gene, were used to genotype
      the germplasm. The haplotype marker data and phenotypic PHS data were compared
      across all cultivars and different production regions. A relative change in
      observed phenotypic variation percentage was obtained per marker allele and
      across marker haplotype combinations when compared to the PHS susceptible
      cultivar, Tugela-DN. Clear favorable haplotypes, contributing 40-60% of the
      variation for PHS tolerance, were identified for QTL 3A and 4A. Initial analyses
      show haplotype data appear to be predictive of PHS tolerance status and germplasm
      can now be selected to improve PHS tolerance. These haplotype data are the first
      of its kind for PHS genotyping in South Africa. In future, this can be used as a
      tool to predict the possible PHS tolerance range of a new cultivar.

PMID- 29449854
TI  - Genome-Wide Characterization of bHLH Genes in Grape and Analysis of their
      Potential Relevance to Abiotic Stress Tolerance and Secondary Metabolite
      Biosynthesis.
AB  - Basic helix-loop-helix (bHLH) transcription factors are involved in many abiotic
      stress responses as well as flavonol and anthocyanin biosynthesis. In grapes
      (Vitis vinifera L.), flavonols including anthocyanins and condensed tannins are
      most abundant in the skins of the berries. Flavonols are important phytochemicals
      for viticulture and enology, but grape bHLH genes have rarely been examined. We
      identified 94 grape bHLH genes in a genome-wide analysis and performed Nr and GO
      function analyses for these genes. Phylogenetic analyses placed the genes into 15
      clades, with some remaining orphans. 41 duplicate gene pairs were found in the
      grape bHLH gene family, and all of these duplicate gene pairs underwent purifying
      selection. Nine triplicate gene groups were found in the grape bHLH gene family
      and all of these triplicate gene groups underwent purifying selection. Twenty-two
      grape bHLH genes could be induced by PEG treatment and 17 grape bHLH genes could
      be induced by cold stress treatment including a homologous form of MYC2,
      VvbHLH007. Based on the GO or Nr function annotations, we found three other genes
      that are potentially related to anthocyanin or flavonol biosynthesis: VvbHLH003,
      VvbHLH007, and VvbHLH010. We also performed a cis-acting regulatory element
      analysis on some genes involved in flavonoid or anthocyanin biosynthesis and our
      results showed that most of these gene promoters contained G-box or E-box
      elements that could be recognized by bHLH family members.

PMID- 29449855
TI  - MicroRNA160 Modulates Plant Development and Heat Shock Protein Gene Expression to
      Mediate Heat Tolerance in Arabidopsis.
AB  - Global warming is causing a negative impact on plant growth and adversely impacts
      on crop yield. MicroRNAs (miRNAs) are critical in regulating the expression of
      genes involved in plant development as well as defense responses. The effects of
      miRNAs on heat-stressed Arabidopsis warrants further investigation. Heat stress
      increased the expression of miR160 and its precursors but considerably reduced
      that of its targets, ARF10, ARF16, and ARF17. To study the roles of miR160 during
      heat stress, transgenic Arabidopsis plants overexpressing miR160 precursor a
      (160OE) and artificial miR160 (MIM160), which mimics an inhibitor of miR160, were
      created. T-DNA insertion mutants of miR160 targets were also used to examine
      their tolerances to heat stress. Results presented that overexpressing miR160
      improved seed germination and seedling survival under heat stress. The lengths of
      hypocotyl elongation and rachis were also longer in 160OE than the wild-type (WT)
      plants under heat stress. Interestingly, MIM160 plants showed worse adaption to
      heat. In addition, arf10, arf16, and arf17 mutants presented similar phenotypes
      to 160OE under heat stress to advance abilities of thermotolerance. Moreover,
      transcriptome and qRT-PCR analyses revealed that HSP17.6A, HSP17.6II, HSP21, and
      HSP70B expression levels were regulated by heat in 160OE, MIM160, arf10, arf16,
      and arf17 plants. Hence, miR160 altered the expression of the heat shock proteins
      and plant development to allow plants to survive heat stress.

PMID- 29449856
TI  - Efficient Detection of Long dsRNA in Vitro and in Vivo Using the dsRNA Binding
      Domain from FHV B2 Protein.
AB  - Double-stranded RNA (dsRNA) plays essential functions in many biological
      processes, including the activation of innate immune responses and RNA
      interference. dsRNA also represents the genetic entity of some viruses and is a
      hallmark of infections by positive-sense single-stranded RNA viruses. Methods for
      detecting dsRNA rely essentially on immunological approaches and their use is
      often limited to in vitro applications, although recent developments have allowed
      the visualization of dsRNA in vivo. Here, we report the sensitive and rapid
      detection of long dsRNA both in vitro and in vivo using the dsRNA binding domain
      of the B2 protein from Flock house virus. In vitro, we adapted the system for the
      detection of dsRNA either enzymatically by northwestern blotting or by direct
      fluorescence labeling on fixed samples. In vivo, we produced stable transgenic
      Nicotiana benthamiana lines allowing the visualization of dsRNA by fluorescence
      microscopy. Using these techniques, we were able to discriminate healthy and
      positive-sense single-stranded RNA virus-infected material in plants and insect
      cells. In N. benthamiana, our system proved to be very potent for the spatio
      temporal visualization of replicative RNA intermediates of a broad range of
      positive-sense RNA viruses, including high- vs. low-copy number viruses.

PMID- 29449857
TI  - Plastid Genome Comparative and Phylogenetic Analyses of the Key Genera in
      Fagaceae: Highlighting the Effect of Codon Composition Bias in Phylogenetic
      Inference.
AB  - Fagaceae is one of the largest and economically important taxa within Fagales.
      Considering the incongruence among inferences from plastid and nuclear genes in
      the previous Fagaceae phylogeny studies, we assess the performance of plastid
      phylogenomics in this complex family. We sequenced and assembled four complete
      plastid genomes (Fagus engleriana, Quercus spinosa, Quercus aquifolioides, and
      Quercus glauca) using reference-guided assembly approach. All of the other 12
      published plastid genomes in Fagaceae were retrieved for genomic analyses
      (including repeats, sequence divergence and codon usage) and phylogenetic
      inference. The genomic analyses reveal that plastid genomes in Fagaceae are
      conserved. Comparing the phylogenetic relationships of the key genera in Fagaceae
      inferred from different codon positions and gene function datasets, we found that
      the first two codon sites dataset recovered nearly all relationships and received
      high support. Thus, the result suggested that codon composition bias had great
      influence on Fagaceae phylogenetic inference. Our study not only provides basic
      understanding of Fagaceae plastid genomes, but also illuminates the effectiveness
      of plastid phylogenomics in resolving relationships of this intractable family.

PMID- 29449858
TI  - Exogenous Hydrogen Peroxide Contributes to Heme Oxygenase-1 Delaying Programmed
      Cell Death in Isolated Aleurone Layers of Rice Subjected to Drought Stress in a
      cGMP-Dependent Manner.
AB  - Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that plays a dual
      role in plant cells. Here, we discovered that drought (20% polyethylene glycol
      6000, PEG)-triggered decreases of HO-1 transcript expression and HO activity.
      However, exogenous H2O2 contributed toward the increase in HO-1 gene expression
      and activity of the enzyme under drought stress. Meanwhile, the HO-1 inducer
      hematin could mimic the effects of the H2O2 scavengers ascorbic acid (AsA) and
      dimethylthiourea (DMTU) and the H2O2 synthesis inhibitor diphenyleneiodonium
      (DPI) for scavenging or diminishing drought-induced endogenous H2O2. Conversely,
      the zinc protoporphyrin IX (ZnPPIX), an HO-1-specific inhibitor, reversed the
      effects of hematin. We further analyzed the endogenous H2O2 levels and HO-1
      transcript expression levels of aleurone layers treated with AsA, DMTU, and DPI
      in the presence of exogenous H2O2 under drought stress, respectively. The results
      showed that in aleurone layers subjected to drought stress, when the endogenous
      H2O2 level was inhibited, the effect of exogenous H2O2 on the induction of HO-1
      was enhanced. Furthermore, exogenous H2O2-activated HO-1 effectively enhanced
      amylase activity. Application of 8-bromoguanosine 3',5'-cyclic guanosine
      monophosphate (8-Br-cGMP) (the membrane permeable cGMP analog) promoted the
      effect of exogenous H2O2-delayed PCD of aleurone layers in response to drought
      stress. More importantly, HO-1 delayed the programmed cell death (PCD) of
      aleurone layers by cooperating with nitric oxide (NO), and the delayed effect of
      NO on PCD was achieved via mediation by cGMP under drought stress. In short, in
      rice aleurone layers, exogenous H2O2 (as a signaling molecule) triggered HO-1 and
      delayed PCD via cGMP which possibly induced amylase activity under drought
      stress. In contrast, as a toxic by-product of cellular metabolism, the drought
      generated H2O2 promoted cell death.

PMID- 29449859
TI  - Latitudinal Patterns in European Seagrass Carbon Reserves: Influence of Seasonal
      Fluctuations versus Short-Term Stress and Disturbance Events.
AB  - Seagrass meadows form highly productive and valuable ecosystems in the marine
      environment. Throughout the year, seagrass meadows are exposed to abiotic and
      biotic variations linked to (i) seasonal fluctuations, (ii) short-term stress
      events such as, e.g., local nutrient enrichment, and (iii) small-scale
      disturbances such as, e.g., biomass removal by grazing. We hypothesized that
      short-term stress events and small-scale disturbances may affect seagrass chance
      for survival in temperate latitudes. To test this hypothesis we focused on
      seagrass carbon reserves in the form of starch stored seasonally in rhizomes, as
      these have been defined as a good indicator for winter survival. Twelve Zostera
      noltei meadows were monitored along a latitudinal gradient in Western Europe to
      firstly assess the seasonal change of their rhizomal starch content. Secondly, we
      tested the effects of nutrient enrichment and/or biomass removal on the
      corresponding starch content by using a short-term manipulative field experiment
      at a single latitude in the Netherlands. At the end of the growing season, we
      observed a weak but significant linear increase of starch content along the
      latitudinal gradient from south to north. This agrees with the contention that
      such reserves are essential for regrowth after winter, which is more severe in
      the north. In addition, we also observed a weak but significant positive
      relationship between starch content at the beginning of the growing season and
      past winter temperatures. This implies a lower regrowth potential after severe
      winters, due to diminished starch content at the beginning of the growing season.
      Short-term stress and disturbances may intensify these patterns, because our
      manipulative experiments show that when nutrient enrichment and biomass loss co
      occurred at the end of the growing season, Z. noltei starch content declined. In
      temperate zones, the capacity of seagrasses to accumulate carbon reserves is
      expected to determine carbon-based regrowth after winter. Therefore, processes
      affecting those reserves might affect seagrass resilience. With increasing human
      pressure on coastal systems, short- and small-scale stress events are expected to
      become more frequent, threatening the resilience of seagrass ecosystems,
      particularly at higher latitudes, where populations tend to have an annual cycle
      highly dependent on their storage capacity.

PMID- 29449860
TI  - Adaptive Genetic Divergence Despite Significant Isolation-by-Distance in
      Populations of Taiwan Cow-Tail Fir (Keteleeria davidiana var. formosana).
AB  - Double digest restriction site-associated DNA sequencing (ddRADseq) is a tool for
      delivering genome-wide single nucleotide polymorphism (SNP) markers for non-model
      organisms useful in resolving fine-scale population structure and detecting
      signatures of selection. This study performs population genetic analysis, based
      on ddRADseq data, of a coniferous species, Keteleeria davidiana var. formosana,
      disjunctly distributed in northern and southern Taiwan, for investigation of
      population adaptive divergence in response to environmental heterogeneity. A
      total of 13,914 SNPs were detected and used to assess genetic diversity, FST
      outlier detection, population genetic structure, and individual assignments of
      five populations (62 individuals) of K. davidiana var. formosana. Principal
      component analysis (PCA), individual assignments, and the neighbor-joining tree
      were successful in differentiating individuals between northern and southern
      populations of K. davidiana var. formosana, but apparent gene flow between the
      southern DW30 population and northern populations was also revealed. Fifteen of
      23 highly differentiated SNPs identified were found to be strongly associated
      with environmental variables, suggesting isolation-by-environment (IBE). However,
      multiple matrix regression with randomization analysis revealed strong IBE as
      well as significant isolation-by-distance. Environmental impacts on divergence
      were found between populations of the North and South regions and also between
      the two southern neighboring populations. BLASTN annotation of the sequences
      flanking outlier SNPs gave significant hits for three of 23 markers that might
      have biological relevance to mitochondrial homeostasis involved in the survival
      of locally adapted lineages. Species delimitation between K. davidiana var.
      formosana and its ancestor, K. davidiana, was also examined (72 individuals).
      This study has produced highly informative population genomic data for the
      understanding of population attributes, such as diversity, connectivity, and
      adaptive divergence associated with large- and small-scale environmental
      heterogeneity in K. davidiana var. formosana.

PMID- 29449861
TI  - Application of Electrical Capacitance Method for Prediction of Plant Root Mass
      and Activity in Field-Grown Crops.
AB  - The root electrical capacitance (C R ) method is suitable for assessing root
      growth and activity, but soil water content (SWC) strongly influences the
      measurement results. This study aimed to adapt the method for field monitoring by
      evaluating the effect of SWC on root capacitance to ensure the comparability of C
      R detected at different SWC. First a pot experiment was conducted with maize and
      soybean to establish C R -SWC functions for the field soil. Ontogenetic changes
      in root activity were monitored under field conditions by simultaneously
      measuring C R and SWC around the roots. The C R values were normalized using SWC
      data and experimental C R -SWC functions to obtain C R*, the comparable indicator
      of root activity. The effect of arbuscular mycorrhizal fungi (AMF) inoculation on
      the C R* and biomass of field-grown soybean was investigated. The pot trial
      showed an exponential increase in C R with SWC. C R -SWC functions proved to be
      species-specific. C R showed strong correlation with root dry mass (R2 = 0.83
      0.87). The root activity (C R*) of field-grown crops increased until flowering,
      then decreased during maturity. This was consistent with data obtained with other
      methods. AMF inoculation of soybean resulted in significantly higher C R* during
      the late vegetative and early flowering stages, when destructive sampling
      concurrently showed higher shoot biomass. The results demonstrated that the root
      capacitance method could be useful for time course studies on root activity under
      field conditions, and for comparing single-time capacitance data collected in
      areas with heterogeneous soil water status.

PMID- 29449862
TI  - Characterization of Transcription Factor Gene OsDRAP1 Conferring Drought
      Tolerance in Rice.
AB  - HIGHLIGHTS Overexpressing and RNA interfering OsDRAP1 transgenic rice plants
      exhibited significantly improved and reduced drought tolerance, but accompanied
      with negative effects on development and yield. The dehydration responsive
      element binding (DREBs) genes are important transcription factors which play a
      crucial role in plant abiotic stress tolerances. In this study, we functionally
      characterized a DREB2-like gene, OsDRAP1 conferring drought tolerance (DT) in
      rice. OsDRAP1, containing many cis-elements in its promoter region, was expressed
      in all organs (mainly expressed in vascular tissues) of rice, and induced by a
      variety of environmental stresses and plant hormones. Overexpressing OsDRAP1
      transgenic plants exhibited significantly improved DT; while OsDRAP1 RNA
      interfering plants exhibited significantly reduced DT which also accompanied with
      significant negative effects on development and yield. Overexpression of OsDRAP1
      has a positive impact on maintaining water balance, redox homeostasis and
      vascular development in transgenic rice plants under drought stress. OsDRAP1
      interacted with many genes/proteins and could activate many downstream DT related
      genes, including important transcription factors such as OsCBSX3 to response
      drought stress, indicating the OsDRAP1-mediated pathways for DT involve complex
      genes networks. All these results provide a basis for further complete
      understanding of the OsDRAP1 mediated gene networks and their related phenotypic
      effects.

PMID- 29449863
TI  - Experimental assessment of a 3-D plenoptic endoscopic imaging system.
AB  - An endoscopic imaging system using a plenoptic technique to reconstruct 3-D
      information is demonstrated and analyzed in this Letter. The proposed setup
      integrates a clinical surgical endoscope with a plenoptic camera to achieve a
      depth accuracy error of about 1 mm and a precision error of about 2 mm, within a
      25 mm * 25 mm field of view, operating at 11 frames per second.

PMID- 29449864
TI  - Seasonal variation in circulating group 2 innate lymphoid cells in mugwort
      allergic asthmatics during and outside pollen season.
AB  - Background: Group 2 innate lymphoid cells (ILC2s) are a newly identified cell
      population with the potent capability to produce Th2-type cytokines in a non
      antigen specific manner. Previous study demonstrated that enhanced circulating
      ILC2s in cat-allergic patient after experimental allergen challenge, whereas the
      effects of natural allergen exposure on peripheral ILC2s are still unclear. We
      therefore examined the variations in circulating ILC2s among asthmatic patients
      sensitized to different allergens in- and outside- pollen season. Methods: 10
      patients sensitized to mugwort, 10 patients sensitized to house dust mites (HDM)
      and 12 healthy controls were recruited into this study. Blood samples were
      collected from the patients in- and outside- pollens season, 2-3 months apart.
      ILC2s (Lin-CD127+ CRTH2+) were enumerated by flow cytometry, as well as
      intracellular IL-5 and IL-13 expression. The levels of IL-5 and IL-13 in
      supernatants of Lineage- and Lineage+ cells stimulated with IL-25 and/or IL-33 in
      the presence of IL-2 were measured using a Milliplex human cytokine array kit.
      Results: An obvious seasonal increases in percentages of total and IL-13+ ILC2s
      were observed in patients with mugwort sensitization during natural pollen
      exposure, however, the percentages of peripheral ILC2s in HDM-allergic patients
      were not affected significantly. A positive correlation between FeNO and IL
      13+ILC2s was found in patients sensitized to mugwort. A mixture of IL-33 and IL
      25 induced a significant production of IL-13 and IL-5 from Lineage- cells of both
      mugwort-allergic and HDM-allergic asthmatics. Stimulation with IL-33 alone
      induced a significantly greater quantity of IL-13 by Lineage-cells from mugwort
      allergic asthmatic compared with that from HDM-allergic asthmatics, whereas IL-25
      induced a significantly greater amount of IL-5 by the Lineage-cells from mugwort
      allergic asthmatic compared with that from HDM-allergic asthmatics. Conclusion:
      Within pollen season the frequencies and function profiles of circulating ILC2s
      among asthmatic children are altered dynamically, which may be closely related to
      the sensitized type of allergens.

PMID- 29449865
TI  - Correction to: development of foraging skills in two orangutan populations:
      needing to learn or needing to grow?
AB  - [This corrects the article DOI: 10.1186/s12983-016-0178-5.].

PMID- 29449866
TI  - Correction to: getting fat or getting help? how female mammals cope with
      energetic constraints on reproduction.
AB  - [This corrects the article DOI: 10.1186/s12983-017-0214-0.].

PMID- 29449868
TI  - Prediction of Methionine and Homocysteine levels in Zucker diabetic fatty (ZDF)
      rats as a T2DM animal model after consumption of a Methionine-rich diet.
AB  - Background: Although alterations in the methionine metabolism cycle (MMC) have
      been associated with vascular complications of diabetes, there have not been
      consistent results about the levels of methionine and homocysteine in type 2
      diabetes mellitus (T2DM). The aim of the current study was to predict changes in
      plasma methionine and homocysteine concentrations after simulated consumption of
      methionine-rich foods, following the development of a mathematical model for MMC
      in Zucker Diabetic Fatty (ZDF) rats, as a representative T2DM animal model.
      Method: The model building and simulation were performed using NONMEM(r) (ver.
      7.3.0) assisted by Perl-Speaks-NONMEM (PsN, ver. 4.3.0). Model parameters were
      derived using first-order conditional estimation method with interactions
      permitted among the parameters (FOCE-INTER). NCA was conducted using Phoenix
      (ver. 6.4.0). For all tests, we considered a P-value < 0.05 to reflect
      statistical significance. Results: Our model featured seven compartments that
      considered all parts of the cycle by applying non-linear mixed effects model.
      Conversion of S-adenosyl-L-homocysteine (SAH) to homocysteine increased and the
      metabolism of homocysteine was reduced under diabetic conditions, and
      consequently homocysteine accumulated in the elimination phase.Using our model,
      we performed simulations to compare the changes in plasma methionine and
      homocysteine concentrations between ZDF and normal rats, by multiple
      administrations of the methionine-rich diet of 1 mmol/kg, daily for 60 days. The
      levels of methionine and homocysteine were elevated approximately two- and three
      fold, respectively, in ZDF rats, while there were no changes observed in the
      normal control rats. Conclusion: These results can be interpreted to mean that
      both methionine and homocysteine will accumulate in patients with T2DM, who
      regularly consume high-methionine foods.

PMID- 29449869
TI  - Off-label prescription of psychiatric drugs by non-psychiatrist physicians in
      three general hospitals in Germany.
AB  - Background: Off-label prescribing of psychoactive drugs is a common practice in
      psychiatry. Here, we sought to investigate the frequency of off-label prescribing
      in a population of hospitalized patients with a somatic illness who were also
      suffering from a psychiatric pathology. Methods: Using a prospective,
      observational design, we collected data from 982 hospitalized patients with a
      somatic illness for whom a psychiatric consultation was requested because of the
      presence of additional psychiatric symptoms. Data were collected at three
      hospitals in Germany. Demographic and clinical data, including the previous
      psychoactive medications and an assessment of the suitability of the previous
      medications, were recorded and analyzed. Results: Data on the previous
      psychiatric medications were available for 972 patients. In 16.6% of patients, at
      least one psychoactive drug had been prescribed off-label, 20.2% had received on
      label medication, and 63.2% had not received any psychiatric medication. Among
      all patients receiving psychiatric medication, 45.1% had received off-label
      medication. The logistic regression analysis showed a significant influence of
      age on the likelihood of receiving off-label medication (p = 0.018).
      Benzodiazepines were the most frequent off-label prescription (25.8% of off-label
      prescriptions), followed by atypical antipsychotics (18.2%) and low-potency
      antipsychotics (17.2%). Notably, 57.1% of off-label prescriptions were judged to
      be 'not indicated' by experienced psychiatrists. Conclusions: Our data show a
      high frequency of the off-label prescription of psychoactive drugs by physicians
      treating patients with somatic illnesses in general hospitals. Because more than
      half of these cases were judged to be "not indicated", these prescriptions
      indicate a potential risk to patients. Furthermore, the classes of drugs that
      were most frequently prescribed off-label, benzodiazepines and antipsychotics,
      both show a substantial risk profile, particularly for elderly patients.

PMID- 29449867
TI  - Current therapies in alleviating liver disorders and cancers with a special focus
      on the potential of vitamin D.
AB  - Background: Liver dysfunction is a topic of global concern with many advancing
      therapies being researched. Though vitamin D takes a center place, other
      therapies especially nutritional are also gaining ground. Vitamin D has gone
      beyond its role in skeletal disorders by showcasing its associations in other
      metabolic dysfunctions too. Result: Epidemiological evidences show a correlation
      between the status of vitamin D and different forms of cancer. Vitamin D
      receptors and alterations in gene expression appear decisive in the development
      of chronic liver disorders. Nutritional status therefore plays a significant role
      in avoiding the complications related to liver dysfunctions, making it mandatory
      in maintaining vitamin D sufficiency in the body. Therapies with omega-3 fatty
      acids, antioxidants, amino acids, steroids also render benefits which could be
      further explored. Recent research on the progression of certain forms of liver
      cancer using vitamin D analogs like Seocalcitol EB 1089 has shown good promise.
      Conclusion: The anti-inflammatory and immuno- regulatory properties of vitamin D
      makes its analogs, suitable candidates of better choice for the prevention and
      treatment of liver disorders and cancer.

PMID- 29449870
TI  - Validating the Demand Control Support Questionnaire among white-collar employees
      in Switzerland and the United States.
AB  - Background: The Demand Control Support Questionnaire (DCSQ) is an established
      self-reported tool to measure a stressful work environment. Validated German and
      English versions are however currently missing. The aim of this study was
      therefore to evaluate the psychometric properties of German and English versions
      of the DCSQ among white-collar employees in Switzerland and the US. Methods: This
      cross-sectional study was carried out on 499 employees in Switzerland and 411 in
      the US, respectively. The 17-item DCSQ with three scales assessed psychosocial
      stress at work (psychological demands, decision latitude, and social support at
      work). Depressive symptoms were measured by the 2-item Patient Health
      Questionnaire. Cronbach's alpha and item-total correlations tested the scale
      reliability (internal consistency). Construct validity of the questionnaire was
      examined using exploratory factor analysis (EFA). Logistic regressions estimated
      associations of each scale and job strain with depressive symptoms (criterion
      validity). Results: In both samples, all DCSQ scales presented satisfactory
      internal consistency (Cronbach's alpha >= 0.72; item-total correlations >= 0.33),
      and EFA showed the 17 items loading on three factors, which is in line with the
      theoretically assumed structure of the DCSQ construct. Moreover, all three scales
      as well as high job strain were significantly associated with depressive
      symptoms. The associations were stronger in the US sample. Conclusions: The
      German and the English versions of the DCSQ seem to be reliable and valid
      instruments to measure psychosocial stress based on the job demand-control
      support model in the workplace of white-collar employees in Switzerland and the
      US.

PMID- 29449871
TI  - The elastic modulus for maize stems.
AB  - Background: Stalk lodging is a serious challenge in the production of maize and
      sorghum. A comprehensive understanding of lodging will likely require accurate
      characterizations of the mechanical properties of such plants. One of the most
      important mechanical properties for structural analysis of bending is the modulus
      of elasticity. The purpose of this study was to measure the modulus of elasticity
      of dry, mature maize rind tissues using three different loading modes (bending,
      compression and tensile), and to determine the accuracy and reliability of each
      test method. Results: The three testing modes produced comparable elastic modulus
      values. For the sample in this study, modulus values ranged between 6 and 16 GPa.
      All three testing modes exhibited relatively favorable repeatability (i.e. test
      to-test variation of < 5%). Modulus values of internodal specimens were
      significantly higher than specimens consisting of both nodal and internodal
      tissues, indicating spatial variation in the modulus of elasticity between the
      nodal and internodal regions. Conclusions: Bending tests were found to be the
      least labor intensive method and also demonstrated the best test-to-test
      repeatability. This test provides a single aggregate stiffness value for an
      entire stalk. Compression tests were able to determine more localized (i.e.,
      spatially dependent) modulus of elasticity values, but required additional sample
      preparation and test time. Finally, tensile tests provided the most focused
      measurements of the modulus of elasticity, but required the longest sample
      preparation time.

PMID- 29449872
TI  - Citizen crowds and experts: observer variability in image-based plant
      phenotyping.
AB  - Background: Image-based plant phenotyping has become a powerful tool in
      unravelling genotype-environment interactions. The utilization of image analysis
      and machine learning have become paramount in extracting data stemming from
      phenotyping experiments. Yet we rely on observer (a human expert) input to
      perform the phenotyping process. We assume such input to be a 'gold-standard' and
      use it to evaluate software and algorithms and to train learning-based
      algorithms. However, we should consider whether any variability among experienced
      and non-experienced (including plain citizens) observers exists. Here we design a
      study that measures such variability in an annotation task of an integer
      quantifiable phenotype: the leaf count. Results: We compare several experienced
      and non-experienced observers in annotating leaf counts in images of Arabidopsis
      Thaliana to measure intra- and inter-observer variability in a controlled study
      using specially designed annotation tools but also citizens using a distributed
      citizen-powered web-based platform. In the controlled study observers counted
      leaves by looking at top-view images, which were taken with low and high
      resolution optics. We assessed whether the utilization of tools specifically
      designed for this task can help to reduce such variability. We found that the
      presence of tools helps to reduce intra-observer variability, and that although
      intra- and inter-observer variability is present it does not have any effect on
      longitudinal leaf count trend statistical assessments. We compared the
      variability of citizen provided annotations (from the web-based platform) and
      found that plain citizens can provide statistically accurate leaf counts. We also
      compared a recent machine-learning based leaf counting algorithm and found that
      while close in performance it is still not within inter-observer variability.
      Conclusions: While expertise of the observer plays a role, if sufficient
      statistical power is present, a collection of non-experienced users and even
      citizens can be included in image-based phenotyping annotation tasks as long they
      are suitably designed. We hope with these findings that we can re-evaluate the
      expectations that we have from automated algorithms: as long as they perform
      within observer variability they can be considered a suitable alternative. In
      addition, we hope to invigorate an interest in introducing suitably designed
      tasks on citizen powered platforms not only to obtain useful information (for
      research) but to help engage the public in this societal important problem.

PMID- 29449873
TI  - A novel rejuvenation approach to induce endohormones and improve rhizogenesis in
      mature Juglans tree.
AB  - Background: Juglans is a difficult-to-root tree. In the present study, we
      successfully rejuvenated stock plants by grafting and then burying them
      horizontally. Results: Rooting rates of rejuvenated shoots were 98.1% 20 days
      after cutting. We recorded spatial and temporal variation in endogenous indole-3
      acetic acid (IAA), abscisic acid (ABA), gibberellin A3 (GA3) and zeatin-riboside
      (ZR) under root induction. The four types of endohormones were mainly confined to
      the phloem sieve and companion cells (S&Cs) at the base of either rejuvenated or
      mature soft shoots. IAA and ABA levels were higher in rejuvenated shoots than in
      mature shoots, whereas the opposite was true for GA3 and ZR. During rooting
      induction, GA3 was the first hormone to be observed outside phloem S&Cs, followed
      by IAA, ABA and ZR. In rejuvenating soft shoots, IAA accumulated in the cross
      sectional areas of the cambium and phloem, where root primordia were evident.
      Conclusions: The improvement in the rooting ability that was evident after
      rejuvenation most likely results a transformation of the plant to a juvenile
      form, from elevated IAA levels in phloem S&Cs and from a promotion of all four
      endohormones outside phloem S&Cs, in particular, from an accumulation of IAA in
      the cross-sectional areas of the cambium and phloem.

PMID- 29449874
TI  - An efficient modified method for plant leaf lipid extraction results in improved
      recovery of phosphatidic acid.
AB  - Background: Lipidomics plays an important role in understanding plant adaptation
      to different stresses and improving our knowledge of the genes underlying lipid
      metabolism. Lipidomics involves lipid extraction, sample preparation, mass
      spectrometry analysis, and data interpretation. One of the practical challenges
      for large-scale lipidomics studies on plant leaves is the requirement of an
      efficient and rapid extraction method. Results: A single-extraction method with a
      polar solvent mixture gives results comparable to a widely used, multi-extraction
      method when tested on both Arabidopsis thaliana and Sorghum bicolor leaf tissue.
      This single-extraction method uses a mixture of 30 parts chloroform, 25 parts
      isopropanol, 41.5 parts methanol, and 3.5 parts water (v/v/v/v) and a 24-h
      extraction time. Neither inclusion of ammonium acetate nor inclusion of acetic
      acid increased extraction efficiency. Conclusions: The extract produced by this
      method can be used for analysis by mass spectrometry without a solvent
      evaporation step. The amount of lipid extracted, including phosphatidic acid, is
      comparable to widely used, more labor-intensive methods. The single-extraction
      protocol is less laborious, reducing the potential for human error.

PMID- 29449875
TI  - A robust vegetation index for remotely assessing chlorophyll content of
      dorsiventral leaves across several species in different seasons.
AB  - Background: Leaf chlorophyll content (LCC) provides valuable information about
      plant physiology. Most of the published chlorophyll vegetation indices at the
      leaf level have been based on the spectral characteristics of the adaxial leaf
      surface, thus, they are not appropriate for estimating LCC when both the adaxial
      and abaxial leaf surfaces influence the spectral reflectance. We attempted to
      address this challenge by measuring the spectral reflectance of the adaxial and
      abaxial leaf surfaces of several plant species at different growth stages using a
      portable field spectroradiometer. The relationships between more than 30
      published reflectance indices with LCC were analyzed to determine which index
      estimated LCC most effectively. Additionally, since the relationships determined
      on one set of samples might have poor predictive performances when applied to
      other samples, a robust wavelength region is required to render the spectral
      index generally applicable, regardless of the leaf surface or plant species.
      Results: The Modified Datt (MDATT) index, which is the ratio of reflectance
      difference defined as (Rlambda3 - Rlambda1)/(Rlambda3 - Rlambda2), exhibited the
      strongest correlation (R2 = 0.856, RMSE = 6.872 MUg/cm2), with LCC of all the
      indices tested when all the leaf samples from the adaxial and abaxial surfaces
      were combined. The optimal wavelength regions, which were derived from the
      contour maps of R2 between the MDATT index and LCC for the datasets of one side
      or both leaf surfaces of each plant species and their intersection, indicated
      that the red-edge to near-infrared wavelength (723-885 nm) was optimal for
      lambda1, while the red-edge region (697-771 nm) was optimal for lambda2 and
      lambda3. In these optimal wavelength regions, when the MDATT index was used to
      estimate LCC, an R2 higher than 0.8 could be obtained. The correlation of the
      MDATT index with LCC was the same when the positions of lambda2 and lambda3 were
      exchanged in the index. Conclusions: MDATT is proposed as an optimal index for
      the remote estimation of vegetation chlorophyll content across several plant
      species in different growth stages when reflectance from both leaf surfaces is
      considered. The red-edge to near-infrared wavelength (723-885 nm) for lambda1, as
      well as the red-edge region (697-771 nm) for lambda2 or lambda3, are considered
      to be the most robust for constructing the MDATT index for estimating LCC,
      regardless of the leaf surface or plant species.

PMID- 29449876
TI  - Authenticity analyses of Rhizoma Paridis using barcoding coupled with high
      resolution melting (Bar-HRM) analysis to control its quality for medicinal plant
      product.
AB  - Background: Rhizoma Paridis (Chonglou) is a commonly used and precious
      traditional Chinese medicine. Paris polyphylla Smith var. yunnanensis (Franch.)
      Hand. -Mazz. and Paris polyphylla Smith var. chinensis (Franch.) Hara are the two
      main sources of Chonglou under the monograph of Rhizoma Paridis in Chinese
      Pharmacopoeia. In the local marketplace, however, this medicine is prone to be
      accidentally contaminated, deliberately substituted or admixed with other species
      that are similar to Rhizoma Paridis in shape and color. Consequently, these
      adulterations might compromise quality control and result in considerable health
      concerns for consumers. This study aims to develop a rapid and sensitive method
      for accurate identification of Rhizoma Paridis and its common adulterants.
      Methods: DNA barcoding coupled with high resolution melting analysis was applied
      in this research to distinguish Rhizoma Paridis from its adulteration. The
      internal transcribed spacer 2 (ITS2) barcode was selected for HRM analysis to
      produce standard melting profile of the selected species. DNA of the tested
      herbal medicines was isolated and their melting profiles were generated and
      compared with the standard melting profile of P. polyphylla var. chinensis.
      Results: The results indicate that the ITS2 molecular regions coupled with HRM
      analysis can effectively differentiate nine herbal species, including two
      authentic origins of Chonglou and their seven common adulterants. Ten herbal
      medicines labeled "Chonglou" obtained from a local market were collected and
      identified with our methods, and their sequence information was analyzed to
      validate the accuracy of HRM analysis. Conclusions: DNA barcoding coupled with
      HRM analysis is a accurate, reliable, rapid, cost-effective and robust tool,
      which could contribute to the quality control of Rhizoma Paridis in the supply
      chain of the natural health product industry (NHP).

PMID- 29449877
TI  - Internationalization of traditional Chinese medicine: current international
      market, internationalization challenges and prospective suggestions.
AB  - Through reviewing the current international market for traditional Chinese
      medicine (TCM), this paper identified the internationalization challenges for
      TCM, including unclear therapeutic material basis and mechanism, difficulty of
      quality control, low preparation level, registration/policy barriers, and
      shortage of intellectual property. To deal with these challenges, suggestions
      were given including: (1) product innovation of TCM (study the TCM by using the
      methods and means of western medicine; innovate the basic theory of TCM; develop
      TCM health product); (2) standard innovation of TCM; (3) building big data
      platform of Chinese medicine (big data platform of TCM preparation; big data
      platform on the quality of TCM).

PMID- 29449878
TI  - Complete chloroplast genome of the medicinal plant Amomum compactum: gene
      organization, comparative analysis, and phylogenetic relationships within
      Zingiberales.
AB  - Background: Amomum compactum is one of the basic species of the traditional
      herbal medicine amomi fructus rotundus, with great pharmacology effect. The
      system position of A. compactum is not clear yet, and the introduction of this
      plant has been hindered by many plant diseases. However, the correlational
      molecular studies are relatively scarce. Methods: The total chloroplast (cp) DNA
      was extracted according to previous studies, and then sequenced by 454 GS FLX
      Titanium platform. Sequence assembly was complished by Newbler. Genome annotation
      was preformed by CPGAVAS and tRNA-SCAN. Then, general characteristics of the A.
      compactum cp genome and genome comparsion with three Zingiberaceae species was
      analyzed by corresponding softwares. Additionally, phylogenetical trees were
      reconstructed, based on the shared protein-coding gene sequences among 15 plant
      taxa by maximum parsimony (MP) and maximum likelihood (ML) methods. Results: The
      A. compactum cp genome with a classic quadripartite structure, consisting of a
      pair of reverse complement repeat regions (IRa/IRb) of 29,824 bp, a large single
      copy (LSC, 88,535 bp) region as well as a small single copy (SSC, 15,370 bp)
      region, is 163,553 bp in total size. The total GC content of this cp genome is
      36.0%. The A. compactum cp genome owns 135 functional genes, that 113 genes are
      unique, containing eighty protein-coding genes, twenty-nine tRNA (transfer RNA)
      genes and four rRNA (ribosomal RNA) genes. Codon usage of the A. compactum cp
      genome is biased toward codons ending with A/T. Total 58 SSR loci and 24 large
      repeats are detected in the A. compactum cp genome. Relative to three other
      Zingiberaceae cp genomes, the A. compactum cp genome exhibits an obvious
      expansion in the IR regions. In A. compactum cp genome, the ycf1 pseudogene is
      2969 bp away from the IRa/SSC border, whereas in other Zingiberaceae species, it
      is only 4-5 bp away from the IRa/SSC border. Comparative cp genome sequences
      analysis of A. compactum with other Zingiberaceae reveals that the gene order and
      gene content differ slightly among Zingiberaceae species. The phylogenetic
      analysis based on 67 protein-coding gene sequences supports the phylogenetic
      position of A. compactum. Conclusions: The study has identified unique features
      of the A. compactum cp genome which would be helpful for us to understand the cp
      genome evolution and offer useful information for phylogenetics and further
      studies of this traditional medicinal plant.

PMID- 29449879
TI  - The impact of Cognitive Processing Therapy on stigma among survivors of sexual
      violence in eastern Democratic Republic of Congo: results from a cluster
      randomized controlled trial.
AB  - Background: Sexual violence is associated with a multitude of poor physical,
      emotional, and social outcomes. Despite reports of stigma by sexual violence
      survivors, limited evidence exists on effective strategies to reduce stigma,
      particularly in conflict-affected settings. We sought to assess the effect of
      group Cognitive Processing Therapy (CPT) on stigma and the extent to which stigma
      might moderate the effectiveness of CPT in treating mental health problems among
      survivors of sexual violence in the Democratic Republic of Congo. Methods: Data
      were drawn from 405 adult female survivors of sexual violence reporting mental
      distress and poor functioning in North and South Kivu. Women were recruited
      through organizations providing psychosocial support and then cluster randomized
      to group CPT or individual support. Women were assessed at baseline, the end of
      treatment, and again six months later. Assessors were masked to women's treatment
      assignment. Linear mixed-effect regression models were used to estimate (1) the
      effect of CPT on feelings of perceived and internalized (felt) stigma, and (2)
      whether felt stigma and discrimination (enacted stigma) moderated the effects of
      CPT on combined depression and anxiety symptoms, posttraumatic stress, and
      functional impairment. Results: Participants receiving CPT experienced moderate
      reductions in felt stigma relative to those in individual support (Cohen's D =
      0.44, p = value = 0.02) following the end of treatment, though this difference
      was no longer significant six-months later (Cohen's D = 0.45, p = value = 0.12).
      Neither felt nor enacted stigma significantly moderated the effect of CPT on
      mental health symptoms or functional impairment. Conclusions: Group cognitive
      behavioral based therapies may be an effective stigma reduction tool for
      survivors of sexual violence. Experiences and perceptions of stigma did not
      hinder therapeutic effects of group psychotherapy on survivors' mental health.
      Trial registration: ClinicalTrials.gov NCT01385163.

PMID- 29449880
TI  - Characterization and engineering of a dual-function diacylglycerol
      acyltransferase in the oleaginous marine diatom Phaeodactylum tricornutum.
AB  - Background: Photosynthetic oleaginous microalgae are promising feedstocks for
      biofuels. Acyl-CoA:diacylglycerol acyltransferases (DGATs) represent rich sources
      for engineering microalgal lipid production. The principal activity of DGATs has
      been defined as a single-function enzyme catalyzing the esterification of
      diacylglycerol with acyl-CoA. Results: A dual-function PtWS/DGAT associated with
      diatom Phaeodactylum tricornutum is discovered in the current study. Distinctive
      to documented microalgal DGAT types, PtWS/DGAT exhibits activities of both a wax
      ester synthase (WS) and a DGAT. WS/DGATs are broadly distributed in microalgae,
      with different topology and phylogeny from those of DGAT1s, DGAT2s, and DGAT3s.
      In vitro and in vivo assays revealed that PtWS/DGAT, functioning as either a WS
      or a DGAT, exhibited a preference on saturated FA substrate. Endogenous
      overexpression of PtWS/DGAT demonstrated that the DGAT activity was dominant,
      whereas the WS activity was condition dependent and relatively minor. Compared
      with the wild type (WT), overexpression of PtWS/DGAT in the diatom resulted in
      increased levels of total lipids (TL) and triacylglycerol (TAG) regardless of
      nitrogen availability. The stability and scalability of the introduced traits
      were further investigated at a 10-L photobioreactor, where the mutant growth
      resembled WT, with moderately increased productivity of TL and TAG. Furthermore,
      the production of wax esters increased considerably (from undetectable levels to
      2.83%) under nitrogen-deplete conditions. Conclusions: PtWS/DGAT is a
      bifunctional enzyme and may serve as a promising target for the engineering of
      microalga-based oils and waxes for future industrial use.

PMID- 29449881
TI  - A copper-controlled RNA interference system for reversible silencing of target
      genes in Trichoderma reesei.
AB  - Background: Trichoderma reesei is a primary lignocellulosic enzyme producer in
      industry. However, the mechanisms underlying cellulase synthesis as well as other
      physiological processes are insufficiently understood partly due to the
      sophisticated process for its genetic manipulation. Target gene knockdown by RNA
      interference (RNAi) is a powerful tool for genetic research and biotechnology in
      eukaryotes including filamentous fungi. Previously reported RNAi system in T.
      reesei was either uncontrollable or only applicable in certain nutrition state.
      Results: In the present study, we incorporated the copper-responsive tcu1
      promoter into an RNAi-mediated silencing system to develop a controllable RNAi
      mediated silencing system in T. reesei. As the proof-of-concept, a prototrophic
      pyr4 gene, highly expressed cel7a and xyr1 genes induced by Avicel and a fab1
      gene, whose knockout has proved to be intractable, were successfully knocked down
      in the absence of copper when the respective RNAi fragment was expressed.
      Importantly, the phenotype of RNAi strains was shown to be reversed easily to
      mimic the complementation for excluding any unwanted effects resulted from the
      random integration of the hpRNA cassette by adding copper in the media. Thus,
      this controllable RNAi-mediated silencing system can be turned on and turned off
      only depending on the absence and presence of copper ions in the media,
      respectively, and not on the nutritional states. Conclusions: The copper
      controlled RNA interference system represents an effective tool for reversible
      silencing of target genes in T. reesei. This reported strategy to conditionally
      knock down or turn off genes will contribute to our understanding of T. reesei
      gene functions, especially those that are difficult to be knocked out due to
      various reasons. In addition, this simple and cost-effective method holds great
      potential for the application in synthetic biology and genetic engineering of T.
      reesei.

PMID- 29449882
TI  - Mathematical models of lignin biosynthesis.
AB  - Background: Lignin is a natural polymer that is interwoven with cellulose and
      hemicellulose within plant cell walls. Due to this molecular arrangement, lignin
      is a major contributor to the recalcitrance of plant materials with respect to
      the extraction of sugars and their fermentation into ethanol, butanol, and other
      potential bioenergy crops. The lignin biosynthetic pathway is similar, but not
      identical in different plant species. It is in each case comprised of a moderate
      number of enzymatic steps, but its responses to manipulations, such as gene knock
      downs, are complicated by the fact that several of the key enzymes are involved
      in several reaction steps. This feature poses a challenge to bioenergy
      production, as it renders it difficult to select the most promising combinations
      of genetic manipulations for the optimization of lignin composition and amount.
      Results: Here, we present several computational models than can aid in the
      analysis of data characterizing lignin biosynthesis. While minimizing technical
      details, we focus on the questions of what types of data are particularly useful
      for modeling and what genuine benefits the biofuel researcher may gain from the
      resulting models. We demonstrate our analysis with mathematical models for black
      cottonwood (Populus trichocarpa), alfalfa (Medicago truncatula), switchgrass
      (Panicum virgatum) and the grass Brachypodium distachyon. Conclusions: Despite
      commonality in pathway structure, different plant species show different
      regulatory features and distinct spatial and topological characteristics. The
      putative lignin biosynthes pathway is not able to explain the plant specific
      laboratory data, and the necessity of plant specific modeling should be heeded.

PMID- 29449883
TI  - Production of (2R, 3R)-2,3-butanediol using engineered Pichia pastoris: strain
      construction, characterization and fermentation.
AB  - Background: 2,3-butanediol (2,3-BD) is a bulk platform chemical with various
      potential applications such as aviation fuel. 2,3-BD has three optical isomers:
      (2R, 3R)-, (2S, 3S)- and meso-2,3-BD. Optically pure 2,3-BD is a crucial
      precursor for the chiral synthesis and it can also be used as anti-freeze agent
      due to its low freezing point. 2,3-BD has been produced in both native and non
      native hosts. Several pathogenic bacteria were reported to produce 2,3-BD in
      mixture of its optical isomers including Klebsiella pneumoniae and Klebsiella
      oxytoca. Engineered hosts based on episomal plasmid expression such as
      Escherichia coli, Saccharomyces cerevisiae and Bacillus subtilis are not ideal
      for industrial fermentation due to plasmid instability. Results: Pichia pastoris
      is generally regarded as safe and a well-established host for high-level
      heterologous protein production. To produce pure (2R, 3R)-2,3-BD enantiomer, we
      developed a P. pastoris strain by introducing a synthetic pathway. The alsS and
      alsD genes from B. subtilis were codon-optimized and synthesized. The BDH1 gene
      from S. cerevisiae was cloned. These three pathway genes were integrated into the
      genome of P. pastoris and expressed under the control of GAP promoter. Production
      of (2R, 3R)-2,3-BD was achieved using glucose as feedstock. The optical purity of
      (2R, 3R)-2,3-BD was more than 99%. The titer of (2R, 3R)-2,3-BD reached 12 g/L
      with 40 g/L glucose as carbon source in shake flask fermentation. The
      fermentation conditions including pH, agitation speeds and aeration rates were
      optimized in batch cultivations. The highest titer of (2R, 3R)-2,3-BD achieved in
      fed-batch fermentation using YPD media was 45 g/L. The titer of 2,3-BD was
      enhanced to 74.5 g/L through statistical medium optimization. Conclusions: The
      potential of engineering P. pastoris into a microbial cell factory for biofuel
      production was evaluated in this work using (2R, 3R)-2,3-BD as an example.
      Engineered P. pastoris could be a promising workhorse for the production of
      optically pure (2R, 3R)-2,3-BD.

PMID- 29449884
TI  - Improved photobio-H2 production regulated by artificial miRNA targeting psbA in
      green microalga Chlamydomonas reinhardtii.
AB  - Background: Sulfur-deprived cultivation of Chlamydomonas reinhardtii, referred as
      "two-stage culture" transferring the cells from regular algal medium to sulfur
      deplete one, has been extensively studied to improve photobio-H2 production in
      this green microalga. During sulfur-deprivation treatment, the synthesis of a key
      component of photosystem II complex, D1 protein, was inhibited and improved
      photobio-H2 production could be established in C. reinhardtii. However,
      separation of algal cells from a regular liquid culture medium to a sulfur
      deprived one is not only a discontinuous process, but also a cost- and time
      consuming operation. More applicable and economic alternatives for sustained H2
      production by C. reinhardtii are still highly required. Results: In the present
      study, a significant improvement in photobio-H2 production was observed in the
      transgenic green microalga C. reinhardtii, which employed a newly designed
      strategy based on a heat-inducible artificial miRNA (amiRNA) expression system
      targeting D1-encoded gene, psbA. A transgenic algal strain referred as "amiRNA
      D1" has been successfully obtained by transforming the expression vector
      containing a heat-inducible promoter. After heat shock conducted in the same
      algal cultures, the expression of amiRNA-D1 was detected increased 15-fold
      accompanied with a 73% decrease of target gene psbA. More interestingly, this
      transgenic alga accumulated about 60% more H2 content than the wild-type strain
      CC-849 at the end of 7-day cultivation. Conclusions: The photobio-H2 production
      in the engineered transgenic alga was significantly improved. Without imposing
      any nutrient-deprived stress, this novel strategy provided a convenient and
      efficient way for regulation of photobio-H2 production in green microalga by
      simply "turn on" the expression of a designed amiRNA.

PMID- 29449885
TI  - Deep Eutectic Solvents pretreatment of agro-industrial food waste.
AB  - Background: Waste biomass from agro-food industries are a reliable and readily
      exploitable resource. From the circular economy point of view, direct residues
      from these industries exploited for production of fuel/chemicals is a winning
      issue, because it reduces the environmental/cost impact and improves the eco
      sustainability of productions. Results: The present paper reports recent results
      of deep eutectic solvent (DES) pretreatment on a selected group of the agro
      industrial food wastes (AFWs) produced in Europe. In particular, apple residues,
      potato peels, coffee silverskin, and brewer's spent grains were pretreated with
      two DESs, (choline chloride-glycerol and choline chloride-ethylene glycol) for
      fermentable sugar production. Pretreated biomass was enzymatic digested by
      commercial enzymes to produce fermentable sugars. Operating conditions of the DES
      pretreatment were changed in wide intervals. The solid to solvent ratio ranged
      between 1:8 and 1:32, and the temperature between 60 and 150  degrees C. The DES
      reaction time was set at 3 h. Optimal operating conditions were: 3 h pretreatment
      with choline chloride-glycerol at 1:16 biomass to solvent ratio and 115  degrees
      C. Moreover, to assess the expected European amount of fermentable sugars from
      the investigated AFWs, a market analysis was carried out. The overall sugar
      production was about 217 kt yr-1, whose main fraction was from the hydrolysis of
      BSGs pretreated with choline chloride-glycerol DES at the optimal conditions.
      Conclusions: The reported results boost deep investigation on lignocellulosic
      biomass using DES. This investigated new class of solvents is easy to prepare,
      biodegradable and cheaper than ionic liquid. Moreover, they reported good results
      in terms of sugars' release at mild operating conditions (time, temperature and
      pressure).

PMID- 29449886
TI  - Off-label use of IV t-PA in patients with intracranial neoplasm and cavernoma.
AB  - Background: The safety of systemic thrombolysis in patients with intracranial
      tumor and cavernoma are unknown. So far evidence is limited to a number of case
      reports and few case series or unspecified data based on population-based
      analysis. Our aim was to comprehend the risk of systemic thrombolysis in these
      patients. Methods: Patients with additional evidence of intracranial tumor or
      cavernoma who received IV tissue plasminogen activator (t-PA) treatment at our
      comprehensive stroke center over a period of 7 years were identified in our
      stroke database and compared to the same number of matched control subjects
      without any evidence of intracranial tumor and cavernoma. Clinical history and
      imaging patterns before and after t-PA therapy were individually reviewed for
      each patient. Results: Thirty-four patients with additional evidence of
      meningioma (19/34), cavernoma (13/34) or malignant intracranial neoplasm (2/34)
      were identified. The incidence of secondary intracranial hemorrhage observed
      showed no difference between control subjects (9/34, 26%) and patients (6/34,
      18%; p = 0.56). Symptomatic hemorrhage in patients with meningioma or cavernoma
      could not be observed. Likewise, the prevalence of stroke mimics showed no
      difference between patients (8/34, 24%) and control subjects (5/34, 15%; p =
      0.54). However, both patients with malignant intracranial neoplasm presented with
      a stroke mimic and intracranial hemorrhage was observed in one of them.
      Conclusions: In compliance with existing evidence, treatment in patients with
      meningioma and cavernoma appears to be safe and reasonable, while the therapy
      should be avoided in patients with malignant intracranial neoplasm with blood
      brain barrier disruption.

PMID- 29449888
TI  - Towards hope.

PMID- 29449889
TI  - How primary care can contribute to good mental health in adults.
AB  - The need for support for good mental health is enormous. General support for good
      mental health is needed for 100% of the population, and at all stages of life,
      from early childhood to end of life. Focused support is needed for the 17.6% of
      adults who have a mental disorder at any time, including those who also have a
      mental health problem amongst the 30% who report having a long-term condition of
      some kind. All sectors of society and all parts of the NHS need to play their
      part. Primary care cannot do this on its own. This paper describes how primary
      care practitioners can help stimulate such a grand alliance for health, by
      operating at four different levels - as individual practitioners, as
      organisations, as geographic clusters of organisations and as policy-makers.

PMID- 29449890
TI  - Benefits, harms and evidence - reflections from UK primary healthcare.
AB  - : In this paper I examine the relationship between benefits, harms and evidence
      based medicine in the context of British primary healthcare. First, I will
      examine: 'What is a benefit and what is a harm?' Second, what should we know
      about where the balance of risk and benefit appear to lie? Third, what should we
      do with this knowledge, particularly in the context of the biopsychosocial gaze
      of primary care? I conclude that even perfect knowledge about benefits and harms
      requires to be translated in the context of the individual patient: it also
      requires to be interpreted according to what that persons' wishes are. Why this
      matters to me: By reiterating again and again how biases are stacked in favour of
      recommending treatments and interventions well beyond their rational evidence, my
      hope is that more honest medicine will result in less but higher value medicine.
      Stopping doing things that don't work, or work rarely, or come with an
      unacceptable burden of side effects or appointments should make room for the
      pleasure of practicing medicine. Key messages: *Even perfect knowledge about
      benefits and harms requires to be translated in the context of the individual
      patient: it also requires to be interpreted according to what that persons'
      wishes are.*In the real, messy frontline world of general practice, we will
      always have uncertainty about where the balance of risk and benefit might lie.

PMID- 29449887
TI  - Role of the T and B lymphocytes in pathogenesis of autoimmune thyroid diseases.
AB  - Autoimmune thyroid disorders (AITD) broadly include Graves' disease and
      Hashimoto's thyroiditis which are the most common causes of thyroid gland
      dysfunctions. These disorders develop due to complex interactions between
      environmental and genetic factors and are characterized by reactivity to self
      thyroid antigens due to autoreactive lymphocytes escaping tolerance. Both cell
      mediated and humoral responses lead to tissue injury in autoimmune thyroid
      disease. The differentiation of CD4+ cells in the specific setting of immune
      mediators (for example cytokines, chemokines) results in differentiation of
      various T cell subsets. T cell identification has shown a mixed pattern of
      cytokine production indicating that both subtypes of T helper, Th1 and Th2,
      responses are involved in all types of AITD. Furthermore, recent studies
      described T cell subtypes Th17 and Treg which also play an essential role in
      pathogenesis of AITD. This review will focus on the role of the T regulatory
      (Treg) and T helper (Th) (especially Th17) lymphocytes, and also of B lymphocytes
      in AITD pathogenesis. However, we have much more to learn about cellular
      mechanisms and interactions in AITD before we can develop complete understanding
      of AITD pathophysiology.

PMID- 29449891
TI  - Considering change.

PMID- 29449892
TI  - Possible correlation between gut microbiota and immunity among healthy middle
      aged and elderly people in southwest China.
AB  - Background: The present study was conducted to investigate the possible
      association between gut microbes and immunity among healthy middle-aged and
      elderly individuals in southwest China. A total of 148 healthy adults aged >= 50
      years were divided into two age groups: middle-aged group (50-59 years; n = 67,
      54.13 +/- 3.32) and elderly group (>= 60 years; n = 81, 64.70 +/- 3.93). Blood
      samples were collected to measure serum immune and biochemical indices. Gut
      microbiota compositions of the groups were characterized on the basis of faecal
      DNA using 16S rRNA gene sequencing. Results: Among the detected gut microbes, the
      presence of Alistipes was negatively correlated with age in both groups. In the
      middle-aged group, age was negatively correlated with the presence of
      Desulfovibrio and Faecalibacterium. In the elderly group, Coprococcus was present
      at significantly higher levels; age was negatively correlated with the presence
      of Lachnobacterium, Oxalobacter and the Chao index, whereas positively correlated
      with the presence of Sutterella. In the middle-aged group, the presence of
      Bacteroidetes was positively correlated with serum immunoglobulin G (IgG) levels
      and the percent of CD8+ T cells and negatively correlated with the CD4+/CD8+
      ratio; the presence of Firmicutes was negatively correlated with IgM levels;
      Bacteroidetes/Firmicutes ratio was positively correlated with IgG and IgM levels
      and Simpson index was negatively correlated with the percent of CD8+ T cells and
      positively correlated with CD4+/CD8+ ratio. In the elderly group, the presence of
      Verrucomicrobia (identified as genus Akkermansia) was positively correlated with
      IgA levels and the percent of CD8+ T cells and negatively correlated with the
      percent of CD4+ T cells and CD4+/CD8+ ratio; the Chao index and observed species
      were positively correlated with IgA levels. Conclusions: These results indicated
      that ageing could significantly correlate with the composition of gut microbiota
      in terms of quantity and quality. Changes in gut microbiota caused by ageing,
      characterized by decreased Bacteroidetes levels, might be associated with
      immunosenescence among healthy middle-aged and elderly people in southwest China.

PMID- 29449893
TI  - Endoplasmic reticulum stress activation in adipose tissue induces metabolic
      syndrome in individuals with familial partial lipodystrophy of the Dunnigan type.
AB  - Background: Familial partial lipodystrophy of the Dunnigan type is one of the
      most common inherited lipodystrophies variables. These individuals have important
      metabolic disorders that cause predisposition to various diseases. In this study
      we aimed to demonstrate the relation between the metabolic abnormalities,
      inflammatory profile and the expression of genes involved in the activation of
      the endoplasmic reticulum stress (ERS) in subjects with FPLD. Methods: We
      evaluated 14 female FPLD patients and compared with 13 female healthy
      individuals. The subjects were paired with their respective BMI and age and
      categorized into two groups: Familial partial lipodystrophy of the Dunnigan type
      (FPLD) and control. Patients were fasted for 12 h before blood collection for
      measurement of HbA1c, glucose, insulin, lipids and inflammatory markers.
      Subcutaneous adipose tissue was collected by puncture aspiration of submental
      region during ambulatorial surgical aesthetic procedure. Results: We demonstrate
      that patients with FPLD show increased HbA1c (p < 0.01), fasting glucose (p <
      0.002) and triglycerides (p < 0.005) while HDL/cholesterol (p < 0.001) was lower
      when compared to healthy individuals. We found that 64.2% FPLD patients had
      metabolic syndrome according to International Diabetes Federation definition. We
      also observe increased AUC of glucose (p < 0.001) and insulin during oGTT,
      featuring a frame of hyperglycemia and hyperinsulinemia, suggesting insulin
      resistance. Also we found hyperactivation of several genes responsible for ERS
      such as ATF-4 (p < 0.01), ATF-6 (p < 0.01), EIF2alpha3K (p < 0.005), CCT4 (p <
      0.001), CHOP (p < 0.01), CALR (p < 0.001) and CANX (p < 0.005), that corroborate
      the idea that diabetes mellitus and metabolic syndrome are associated with direct
      damage to the endoplasmic reticulum homeostasis. Ultimately, we note that
      individuals with lipodystrophy have an increase in serum interleukins, keys of
      the inflammatory process, as IL-1beta, TNF-alpha and IL-6 (p < 0.05 all),
      compared with healthy individuals, which can be the trigger to insulin resistance
      in this population. Conclusion: Individuals with FPLD besides having typical
      dysfunctions of metabolic syndrome, show a hyperactivation of ERS associated with
      increased systemic inflammatory profile, which together may explain the complex
      clinical aspect of this diseases.Trial registration HCRP no 6711/2012.

PMID- 29449894
TI  - Personalization of regorafenib treatment in metastatic gastrointestinal stromal
      tumours in real-life clinical practice.
AB  - Background: Regorafenib (REG) has now been approved as the standard third-line
      therapy in metastatic gastrointestinal stromal tumour (GIST) patients at the
      recommended dose and schedule of 160 mg once daily for the first 3 weeks of each
      4-week cycle. However, it has a relevant toxicity profile that mainly occurs
      within the first cycles of therapy, and dose and schedule adjustments are often
      required to reduce the frequency or severity of adverse events and to avoid early
      treatment discontinuation. To date, large amounts of data on the use of REG in
      metastatic GIST patients in daily clinical practice are not available, and we
      lack information about how this treatment personalization really affects the
      quality of life (QoL) of patients. The aim of the present retrospective study is
      to build a comprehensive picture of all alternative REG strategies adopted in
      daily clinical practice for use in metastatic GIST patients. Methods: Metastatic
      GIST patients treated with dose adjustment or alternative schedules of REG at
      seven reference Italian centres were retrospectively included. Results: For a
      total of 62 metastatic GIST patients, we confirmed that REG treatment adjustment
      is common in clinical practice and that it is very heterogeneous, with
      approximately 20 different strategies being adopted. Independent of which
      strategy is chosen, treatment personalization has led to a clinical benefit
      defined as complete or partial resolution of side effects in almost all patients,
      affecting the duration of REG treatment. Conclusions: The personalization of REG,
      even if it is heterogeneous, seems to be crucial to maximize the overall
      treatment duration.

PMID- 29449895
TI  - DNM3, p65 and p53 from exosomes represent potential clinical diagnosis markers
      for glioblastoma multiforme.
AB  - Background: Glioblastoma multiforme (GBM) is the most aggressive and deadly
      primary brain cancer that arises from astrocytes and classified as grade IV.
      Recently, exosomes have been reported as an essential mediator in diverse cancer
      carcinogenesis and metastasis. However, their role in GBM is still unclear. In
      this study, we aimed to investigate whether blood exosomes can be potential
      clinical diagnostic markers for GBM. Methods: We used a xenograft orthotopic
      mouse model to detect the differentially expressed genes in the brain and blood
      exosomes of original/recurrent GBM. Results: We found that recurrent GBM had
      stronger growth capacity and lethality than original GBM in the mouse model. A
      gene microarray of original tumors and blood exosomes from GBM orthotopic
      xenografts results showed that DNM3, p65 and CD117 expressions increased, whereas
      PTEN and p53 expressions decreased in both original tumors and blood exosomes. In
      the recurrent GBM tumor model, DNM3 and p65 showed increased expressions, whereas
      ST14 and p53 showed decreased expressions in tumor and blood exosomes of the
      recurrent GBM mouse model. Conclusion: In summary, we found that DNM3, p65 and
      p53 had a similar trend in brain and blood exosomes both for original and
      recurrent GBM, and could serve as potential clinical diagnostic markers for GBM.

PMID- 29449896
TI  - Myxofibrosarcoma primary cultures: molecular and pharmacological profile.
AB  - Background: Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of
      malignant fibrous histiocytoma, is the most common sarcoma of the extremities in
      adults and is characterized by a high frequency of local recurrence. The clinical
      behavior of MFS is unpredictable and the efficacy of chemotherapy is still not
      well documented. Furthermore, given the relatively recent recognition of MFS as a
      distinct pathologic entity its cellular and molecular biology has still not been
      extensively studied in patient-derived preclinical models. We examined the
      molecular biology and treatment outcomes of high-grade, patient-derived MFS
      primary cultures. Methods: A total of three patient-derived MFS primary cultures
      were analyzed. We evaluated the role of CD109 expression and also looked for a
      correlation between transforming growth factor-beta (TGF-beta) expression and
      sensitivity of the primary cultures to different drugs. Results: CD109 was a
      promising marker for the identification of more aggressive high-grade MFS and a
      potential therapeutic target. The results also highlighted the potential role of
      TGF-beta in chemoresistance. Pharmacological analysis confirmed the sensitivity
      of the cultures to chemotherapy. The most active treatments were epirubicin alone
      and epirubicin in combination with ifosfamide, the latter representing the
      current standard of care for soft tissue sarcomas (STSs), including MFS.
      Conclusions: Our results provide a starting point for further research aimed at
      improving the management of MFS patients undergoing chemotherapy.

PMID- 29449897
TI  - Atezolizumab: feasible second-line therapy for patients with non-small cell lung
      cancer? A review of efficacy, safety and place in therapy.
AB  - Advanced non-small cell lung cancer (NSCLC) prognosis is still poor and has
      recently been reformed by the development of immune checkpoint inhibitors and the
      approval of anti-PD-1 (programmed cell-death 1) treatments such as nivolumab and
      pembrolizumab in second line. More recently, atezolizumab (MDPL 3280A), a
      programmed cell-death-ligand 1 (PD-L1) inhibitor, was also studied in this
      setting. Here, we report a review of the literature assessing the efficacy,
      safety, and place of atezolizumab in the second-line treatment of advanced NSCLC.
      We performed a literature search of PubMed, American Society of Clinical
      Oncology, European Society of Medical Oncology and World Conference on Lung
      Cancer meetings. Atezolizumab showed a good tolerance profile and efficacy in
      comparison with docetaxel for second-line treatment of advanced NSCLC. Potential
      predictive biomarkers also have to be assessed.

PMID- 29449898
TI  - Targeted therapy of brain metastases: latest evidence and clinical implications.
AB  - Brain metastases (BM) occur in 20-40% of patients with cancer and 60-75% of
      patients with BM become symptomatic. Due to an aging population and advances in
      the treatment of primary cancers, patients are living longer and are more likely
      to experience complications from BM. The diagnosis of BM drastically worsens long
      term survival rates, with multiple metastases being a poor prognostic factor.
      Until recently, the mainstay of treatment consisted of stereotactic radiosurgery
      (SRS), surgical resection, whole brain radiation therapy (WBRT), or a combination
      of these modalities. Systemic chemotherapy has been felt largely ineffective in
      the treatment of BM due to the presence of the blood-brain barrier (BBB), which
      includes efflux pumps on brain capillaries. Over the past decade however,
      researchers have identified therapeutic agents that are able to cross the BBB.
      These findings could make a multimodality treatment approach possible, consisting
      of surgery, radiation, immunotherapy, and targeted therapy, which could lead to
      better disease control in this patient population and prolong survival. In this
      review, we discuss present evidence on available targeted therapies and their
      role in the treatment of BM from primary tumors with the highest prevalence of
      central nervous system (CNS) involvement, specifically non-small cell lung cancer
      (NSCLC), breast cancer melanoma, and renal cell carcinoma.

PMID- 29449900
TI  - Somatostatin analogs: is one better than other?

PMID- 29449899
TI  - FOXC1 in cancer development and therapy: deciphering its emerging and divergent
      roles.
AB  - Forkhead box C1 (FOXC1) is an essential member of the forkhead box transcription
      factors and has been highlighted as an important transcriptional regulator of
      crucial proteins associated with a wide variety of carcinomas. FOXC1 regulates
      tumor-associated genes and is regulated by multiple pathways that control its
      mRNA expression and protein activity. Aberrant FOXC1 expression is involved in
      diverse tumorigenic processes, such as abnormal cell proliferation, cancer stem
      cell maintenance, cancer migration, and angiogenesis. Herein, we review the
      correlation between the expression of FOXC1 and tumor behaviors. We also
      summarize the mechanisms of the regulation of FOXC1 expression and activity in
      physiological and pathological conditions. In particular, we focus on the
      pathological processes of cancer targeted by FOXC1 and discuss whether FOXC1 is
      good or detrimental during tumor progression. Moreover, FOXC1 is highlighted as a
      clinical biomarker for diagnosis or prognosis in various human cancers. The
      information reviewed here should assist in experimental designs and emphasize the
      potential of FOXC1 as a therapeutic target for cancer.

PMID- 29449901
TI  - Recently integrated Alu insertions in the squirrel monkey (Saimiri) lineage and
      application for population analyses.
AB  - Background: The evolution of Alu elements has been ongoing in primate lineages
      and Alu insertion polymorphisms are widely used in phylogenetic and population
      genetics studies. Alu subfamilies in the squirrel monkey (Saimiri), a New World
      Monkey (NWM), were recently reported. Squirrel monkeys are commonly used in
      biomedical research and often require species identification. The purpose of this
      study was two-fold: 1) Perform locus-specific PCR analyses on recently integrated
      Alu insertions in Saimiri to determine their amplification dynamics, and 2)
      Identify a subset of Alu insertion polymorphisms with species informative allele
      frequency distributions between the Saimiri sciureus and Saimiri boliviensis
      groups. Results: PCR analyses were performed on a DNA panel of 32 squirrel monkey
      individuals for 382 Alu insertion events <=2% diverged from 46 different Alu
      subfamily consensus sequences, 25 Saimiri specific and 21 NWM specific Alu
      subfamilies. Of the 382 loci, 110 were polymorphic for presence / absence among
      squirrel monkey individuals, 35 elements from 14 different Saimiri specific Alu
      subfamilies and 75 elements from 19 different NWM specific Alu subfamilies (13 of
      46 subfamilies analyzed did not contain polymorphic insertions). Of the 110 Alu
      insertion polymorphisms, 51 had species informative allele frequency
      distributions between Saimiri sciureus and Saimiri boliviensis groups.
      Conclusions: This study confirms the evolution of Alu subfamilies in Saimiri and
      provides evidence for an ongoing and prolific expansion of these elements in
      Saimiri with many active subfamilies concurrently propagating. The subset of
      polymorphic Alu insertions with species informative allele frequency distribution
      between Saimiri sciureus and Saimiri boliviensis will be instructive for specimen
      identification and conservation biology.

PMID- 29449902
TI  - SERS-fluorescence bimodal nanoprobes for in vitro imaging of fatty acid
      responsive receptor GPR120.
AB  - G-protein-coupled receptor 120 (GPR120), as a member of the rhodopsin family of G
      protein-coupled receptors, has been shown to function as a sensor for dietary fat
      in the gustatory and digestive systems. Its specific role in the chemoreception
      of fatty acids, which is thought to be crucial in understanding the mechanism
      surrounding the control of fat intake and, accordingly, in the treatment of
      obesity, remains unclear. Here we report a novel surface-enhanced Raman
      spectroscopy (SERS)-fluorescence bimodal microscopic technique for detection and
      imaging of GPR120 in single living cells. CaMoO4:Eu3+@AuNR hybrid nanoparticles
      are synthesized and characterized as imaging probes. Biocompatibility and imaging
      capability of the probes are investigated using a model HEK293 cell line with an
      inducible GPR120 gene transfection. Cellular distribution of GPR120 is visualized
      by single-cell SERS and fluorescence imaging. A dose-dependent GPR120 response to
      linoleic acid treatment is revealed by SERS.

PMID- 29449904
TI  - Expression profiling of chromatin-modifying enzymes and global DNA methylation in
      CD4+ T cells from patients with chronic HIV infection at different HIV control
      and progression states.
AB  - Background: Integration of human immunodeficiency virus type 1 (HIV-1) into the
      host genome causes global disruption of the chromatin environment. The abundance
      level of various chromatin-modifying enzymes produces these alterations and
      affects both the provirus and cellular gene expression. Here, we investigated
      potential changes in enzyme expression and global DNA methylation in chronically
      infected individuals with HIV-1 and compared these changes with non-HIV infected
      individuals. We also evaluated the effect of viral replication and degree of
      disease progression over these changes. Results: Individuals with HIV-1 had a
      significant surge in the expression of DNA and histone methyltransferases (DNMT3A
      and DNMT3B, SETDB1, SUV39H1) compared with non-infected individuals, with the
      exception of PRMT6, which was downregulated. Some histone deacetylases (HDAC2 and
      HDAC3) were also upregulated in patients with HIV. Among individuals with HIV-1
      with various degrees of progression and HIV control, the group of treated
      patients with undetectable viremia showed greater differences with the other two
      groups (untreated HIV-1 controllers and non-controllers). These latter two groups
      exhibited a similar behavior between them. Of interest, the overexpression of
      genes that associate with viral protein Tat (such as SETDB1 along with DNMT3A and
      HDAC1, and SIRT-1) was more prevalent in treated patients. We also observed
      elevated levels of global DNA methylation in individuals with HIV-1 in an inverse
      correlation with the CD4/CD8 ratio. Conclusions: The current study shows an
      increase in chromatin-modifying enzymes and remodelers and in global DNA
      methylation in patients with chronic HIV-1 infection, modulated by various levels
      of viral control and progression.

PMID- 29449905
TI  - Searching for Silver Linings: Is Perceived Medical Discrimination Weaker in
      Segregated Areas?
AB  - An ongoing obstacle in dealing with minority health disparities is discriminatory
      behavior from healthcare practitioners, also known as medical discrimination. It
      is not clear, however, if the effects of medical discriminations onto health are
      constant across space. For example, there is evidence to suspect minorities in
      racially segregated neighborhoods suffer less from discrimination compared to
      those living elsewhere. To determine the presence of spatial heterogeneity
      underlying medical discrimination, we implement logistic geographically weighted
      regression (GWR) using individual data in the city of Philadelphia from the 2006
      and 2008 Public Health Management Corporation's Southeastern Pennsylvania
      Household Health Surveys. Evaluating the potential role residential segregation
      has in offsetting medical discrimination, we compare the GWR results to tract
      data from the 2005-2009 American Community Survey. Through this comparison, we
      find that the effects of medical discrimination on self-rated health are weaker
      in magnitude in areas that are mostly minority. However, evidence of direct
      health benefits for minorities in segregated communities is inconclusive. Thus,
      while we cannot say living in segregated neighborhoods leads to better minority
      health, the sting of medical discrimination can be weaker in these places. These
      results emphasize the importance of local variation, even within a city like
      Philadelphia, challenging the aspatial one-model-fits-all approach normally found
      in population studies.

PMID- 29449903
TI  - Specific or not specific recruitment of DNMTs for DNA methylation, an epigenetic
      dilemma.
AB  - Our current view of DNA methylation processes is strongly moving: First, even if
      it was generally admitted that DNMT3A and DNMT3B are associated with de novo
      methylation and DNMT1 is associated with inheritance DNA methylation, these
      distinctions are now not so clear. Secondly, since one decade, many partners of
      DNMTs have been involved in both the regulation of DNA methylation activity and
      DNMT recruitment on DNA. The high diversity of interactions and the combination
      of these interactions let us to subclass the different DNMT-including complexes.
      For example, the DNMT3L/DNMT3A complex is mainly related to de novo DNA
      methylation in embryonic states, whereas the DNMT1/PCNA/UHRF1 complex is required
      for maintaining global DNA methylation following DNA replication. On the opposite
      to these unspecific DNA methylation machineries (no preferential DNA sequence),
      some recently identified DNMT-including complexes are recruited on specific DNA
      sequences. The coexistence of both types of DNA methylation (un/specific)
      suggests a close cooperation and an orchestration between these systems to
      maintain genome and epigenome integrities. Deregulation of these systems can lead
      to pathologic disorders.

PMID- 29449906
TI  - Elucidating the Vibrational Fingerprint of the Flexible Metal-Organic Framework
      MIL-53(Al) Using a Combined Experimental/Computational Approach.
AB  - In this work, mid-infrared (mid-IR), far-IR, and Raman spectra are presented for
      the distinct (meta)stable phases of the flexible metal-organic framework MIL
      53(Al). Static density functional theory (DFT) simulations are performed,
      allowing for the identification of all IR-active modes, which is unprecedented in
      the low-frequency region. A unique vibrational fingerprint is revealed, resulting
      from aluminum-oxide backbone stretching modes, which can be used to clearly
      distinguish the IR spectra of the closed- and large-pore phases. Furthermore,
      molecular dynamics simulations based on a DFT description of the potential energy
      surface enable determination of the theoretical Raman spectrum of the closed- and
      large-pore phases for the first time. An excellent correspondence between theory
      and experiment is observed. Both the low-frequency IR and Raman spectra show
      major differences in vibrational modes between the closed- and large-pore phases,
      indicating changes in lattice dynamics between the two structures. In addition,
      several collective modes related to the breathing mechanism in MIL-53(Al) are
      identified. In particular, we rationalize the importance of the trampoline-like
      motion of the linker for the phase transition.

PMID- 29449907
TI  - Electrospun Conjugated Polymer/Fullerene Hybrid Fibers: Photoactive Blends,
      Conductivity through Tunneling-AFM, Light Scattering, and Perspective for Their
      Use in Bulk-Heterojunction Organic Solar Cells.
AB  - Hybrid conjugated polymer/fullerene filaments based on MEH-PPV/PVP/PCBM were
      prepared by electrospinning, and their properties were assessed by scanning
      electron, atomic and lateral-force, tunneling, and confocal microscopies, as well
      as by attenuated-total-reflection Fourier transform infrared spectroscopy,
      photoluminescence quantum yield, and spatially resolved fluorescence. Highlighted
      features include the ribbon shape of the realized fibers and the persistence of a
      network serving as a template for heterogeneous active layers in solar cell
      devices. A set of favorable characteristics is evidenced in this way in terms of
      homogeneous charge-transport behavior and formation of effective interfaces for
      diffusion and dissociation of photogenerated excitons. The interaction of the
      organic filaments with light, exhibiting specific light-scattering properties of
      the nanofibrous mat, might also contribute to spreading incident radiation across
      the active layers, thus potentially enhancing photovoltaic performance. This
      method might be applied to other electron donor-electron acceptor material
      systems for the fabrication of solar cell devices enhanced by nanofibrillar
      morphologies embedding conjugated polymers and fullerene compounds.

PMID- 29449908
TI  - PET/CT in the Evaluation of Relapsed or Refractory Hodgkin Lymphoma.
AB  - 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) has been the most
      important advance in the assessment of Hodgkin lymphoma (HL) since the
      introduction of computed tomography (CT). In the frontline management of HL, FDG
      PET combined with low-dose CT has emerged as the modality of choice for staging
      and treatment response assessment. Substantial data have accumulated over the
      past several years supporting the use of PET/CT in the evaluation and management
      of relapsed or refractory HL, as well. In this article, we review the role of
      PET/CT after the frontline treatment of HL, as well as the prognostic utility of
      PET/CT before autologous and allogeneic stem cell transplantation. We also review
      the use of PET/CT as a part of response-adapted treatment strategies in relapsed
      or refractory HL and implications for current and future clinical practice.

PMID- 29449909
TI  - Alterations in the inferior longitudinal fasciculus in autism and associations
      with visual processing: a diffusion-weighted MRI study.
AB  - Background: One of the most reported neural features of autism spectrum disorder
      (ASD) is the alteration of multiple long-range white matter fiber tracts, as
      assessed by diffusion-weighted imaging and indexed by reduced fractional
      anisotropy (FA). Recent methodological advances, however, have shown that this
      same pattern of reduced FA may be an artifact resulting from excessive head
      motion and poorer data quality and that aberrant structural connectivity in
      children with ASD is confined to the right inferior longitudinal fasciculus
      (ILF). This study aimed at replicating the observation of reduced FA along the
      right ILF in ASD, while controlling for group differences in head motion and data
      quality. In addition, we explored associations between reduced FA in the right
      ILF and quantitative ASD characteristics, and the involvement of the right ILF in
      visual processing, which is known to be altered in ASD. Method: Global
      probabilistic tractography was performed on diffusion-weighted imaging data of 17
      adolescent boys with ASD and 17 typically developing boys, matched for age,
      performance IQ, handedness, and data quality. Four tasks were administered to
      measure various aspects of visual information processing, together with
      questionnaires assessing ASD characteristics. Group differences were examined and
      the neural data were integrated with previously published findings using Bayesian
      statistics to quantify evidence for replication and to pool data and thus
      increase statistical power. (Partial) correlations were calculated to investigate
      associations between measures. Results: The ASD group showed consistently reduced
      FA only in the right ILF and slower performance on the visual search task.
      Bayesian statistics pooling data across studies confirmed that group differences
      in FA were confined to the right ILF only, with the evidence for altered FA in
      the left ILF being indecisive. Lower FA in the right ILF tended to covary with
      slower visual search and a more fragmented part-oriented processing style.
      Individual differences in FA of the right ILF were not reliably associated with
      the severity of ASD traits after controlling for clinical status. Conclusion: Our
      findings support the growing evidence for reduced FA along a specific fiber tract
      in ASD, the right ILF.

PMID- 29449910
TI  - Design, Synthesis and Preliminary Antimicrobial Evaluation of N-Alkyl Chain
      Tethered C-5 Functionalized Bis-Isatins.
AB  - A series of N-alkyl tethered C-5 functionalized bis-isatins were synthesized and
      evaluated for antimicrobial activity against pathogenic microorganisms. The
      preliminary evaluation studies revealed the compound 4t, with an optimal
      combination of bromo-substituent at the C-5 position of isatin ring along with
      propyl chain linker being most active among the synthesized series exhibiting an
      IC50 value of 3.72 MUM against Trichomonas vaginalis while 4j exhibited an IC50
      value of 14.8 MUM against Naegleria fowleri, more effective than the standard
      drug Miltefosine. The compound 3f with an octyl spacer length was the most potent
      among the series against Giardia lamblia with an IC50 of 18.4 MUM while 3d
      exhibited an IC50 of 23 MUM against Entamoeba histolytica. This library was also
      screened against the fungal pathogen Aspergillus parasiticus. A number of the
      compounds demonstrated potency against this fungus, illustrating a possible broad
      spectrum activity. Furthermore, an evaluation of these synthesized compounds
      against a panel of normal flora bacteria revealed them to be non-cytotoxic,
      demonstrating the selectivity of these compounds. This observation, in
      combination with previous studies that isatin is non-toxic to humans, presents a
      new possible scaffold for drug discovery against these important protozoal
      pathogens of humans and animals.

PMID- 29449911
TI  - Differences for traits associated with early N acquisition in a grain legume and
      early complementarity in grain legume-triticale mixtures.
AB  - Early strategies of crop growth and N acquisition can be critical for determining
      competitive interactions between weeds and crops. Grain legumes and especially
      lupins are known to be poor competitors against weeds. Grain legumes are known to
      have low mineral soil N uptake abilities. However, inter- and intraspecific
      differences in N uptake ability in relation to below-ground traits have received
      little attention. Our objectives were (i) to measure differences among lupins for
      a set of traits associated with early growth and N acquisition; (ii) to examine
      how this variation compares to differences between lupin and a cereal, triticale,
      and (iii) to assess if mixing lupin with triticale provides a higher potential
      than does pure lupin regarding plant biomass and mineral soil N acquisition early
      in the crop cycle. Lupin (12 genotypes) and triticale plants were grown
      separately and in mixed species pairs in a replacement design for 1 and 2 months
      in three rhizotron experiments. Shoot and root biomass, root length, root
      expansion dynamics, N2 fixation and mineral soil N uptake were measured.
      Differences among lupin species and genotypes regarding traits related to early
      growth and to mineral soil N uptake were observed, but all lupins demonstrated
      slow early growth and low ability to absorb mineral soil N compared to triticale.
      In lupin-triticale mixture, a contrast in early growth strategies between species
      induced a higher total soil mineral N uptake compared with pure lupin.
      Complementarity between lupin and triticale persisted during the second month,
      when interactions began. This complementarity may allow for reduced competition
      between species, favouring higher triticale biomass production than in pure
      triticale, without compromising lupin growth.

PMID- 29449912
TI  - Visualising mouse neuroanatomy and function by metal distribution using laser
      ablation-inductively coupled plasma-mass spectrometry imaging.
AB  - Metals have a number of important roles within the brain. We used laser ablation
      inductively coupled plasma-mass spectrometry (LA-ICP-MS) to map the three
      dimensional concentrations and distributions of transition metals, in particular
      iron (Fe), copper (Cu) and zinc (Zn) within the murine brain. LA-ICP-MS is one of
      the leading analytical tools for measuring metals in tissue samples. Here, we
      present a complete data reduction protocol for measuring metals in biological
      samples, including the application of a pyramidal voxel registration technique to
      reproducibly align tissue sections. We used gold (Au) nanoparticle and ytterbium
      (Yb)-tagged tyrosine hydroxylase antibodies to assess the co-localisation of Fe
      and dopamine throughout the entire mouse brain. We also examined the natural
      clustering of metal concentrations within the murine brain to elucidate areas of
      similar composition. This clustering technique uses a mathematical approach to
      identify multiple 'elemental clusters', avoiding user bias and showing that metal
      composition follows a hierarchical organisation of neuroanatomical structures.
      This work provides new insight into the distinct compartmentalisation of metals
      in the brain, and presents new avenues of exploration with regard to region
      specific, metal-associated neurodegeneration observed in several chronic
      neurodegenerative diseases.

PMID- 29449913
TI  - On-off switch of charge-separated states of pyridine-vinylene-linked porphyrin
      C60 conjugates detected by EPR.
AB  - The design, synthesis, and electronic properties of a new series of D-pi-A
      conjugates consisting of free base (H2P) and zinc porphyrins (ZnP) as electron
      donors and a fullerene (C60) as electron acceptor, in which the two electroactive
      entities are covalently linked through pyridine-vinylene spacers of different
      lengths, are described. Electronic interactions in the ground state were
      characterized by electrochemical and absorption measurements, which were further
      supported with theoretical calculations. Most importantly, charge-transfer bands
      were observed in the absorption spectra, indicating a strong push-pull behavior.
      In the excited states, electronic interactions were detected by selective
      photoexcitation under steady-state conditions, by time-resolved fluorescence
      investigations, and by pump probe experiments on the femto-, pico-, and
      nanosecond time scales. Porphyrin fluorescence is quenched for the different D-pi
      A conjugates, from which we conclude that the deactivation mechanisms of the
      excited singlet states are based on photoinduced energy- and/or electron transfer
      processes between H2P/ZnP and C60, mediated through the molecular spacers. The
      fluorescence intensity decreases and the fluorescence lifetimes shorten as the
      spacer length decreases and as the spacer substitution changes. With the help of
      transient absorption spectroscopy, the formation of charge-separated states
      involving oxidized H2P/ZnP and reduced C60 was confirmed. Lifetimes of the
      corresponding charge-separated states, which ranged from ~400 picoseconds to 165
      nanoseconds, depend on the spacer length, the spacer substitution, and the
      solvent polarity. Interestingly, D-pi-A conjugates containing the longest linkers
      did not necessarily exhibit the longest charge-separated state lifetimes. The
      distances between the electron donors and the acceptors were calculated by
      molecular modelling. The longest charge-separated state lifetime corresponded to
      the D-pi-A conjugate with the longest electron donor-acceptor distance. Likewise,
      EPR measurements in frozen media revealed charge separated states in all the D-pi
      A conjugates investigated. A sharp peak with g values ~2.000 was assigned to
      reduced C60, while a broader, less intense signal (g ~ 2.003) was assigned to
      oxidized H2P/ZnP. On-off switching of the formation and decay of the charge
      separated states was detected by EPR at 77 K by repeatedly turning the
      irradiation source on and off.

PMID- 29449914
TI  - Cycloaddition of cyclobutenone and azomethine imine enabled by chiral isothiourea
      organic catalysts.
AB  - The addition of an organic catalyst to the ketone moiety of a gamma-mono-chloride
      substituted cyclobutenone destroys its stable, conjugated and nearly planar
      structure. The C-C bond in the resulting less stable anionic oxy-substituted non
      planar intermediate is then activated. The breaking of one C-C single bond leads
      to a catalyst-bound intermediate that undergoes alpha-carbon selective reactions
      with azomethine imines to afford nitrogen-containing heterocyclic compounds with
      excellent diastereo- and enantio-selectivities. Our organocatalytic approach
      provides a new reaction pattern for C-C bond activation of cyclobutenones that is
      unavailable with transition metal catalysis. In addition, the present study with
      isothioureas as the organocatalysts expands the potential in using
      organocatalysts for C-C bond breaking and selective reactions.

PMID- 29449915
TI  - NHC-catalysed benzoin condensation - is it all down to the Breslow intermediate?
AB  - The Breslow catalytic cycle describing the benzoin condensation promoted by N
      heterocyclic carbenes (NHC) as proposed in the late 1950s has since then been
      tried by generations of physical organic chemists. Emphasis has been laid on
      proofing the existence of an enaminol like structure (Breslow intermediate) that
      explains the observed umpolung of an otherwise electrophilic aldehyde. The
      present study is not focusing on spectroscopic elucidation of a thiazolydene
      based Breslow intermediate but rather tries to clarify if this key-intermediate
      is indeed directly linked with the product side of the overall reaction. The here
      presented EPR-spectroscopic and computational data provide a fundamentally
      different view on how the benzoin condensation may proceed: a radical pair could
      be identified as a second key-intermediate that is derived from the Breslow
      intermediate via an SET process. These results highlight the close relationship
      to the Cannizarro reaction and oxidative transformations of aldehydes under NHC
      catalysis.

PMID- 29449916
TI  - Critical analysis of the limitations of Bleaney's theory of magnetic anisotropy
      in paramagnetic lanthanide coordination complexes.
AB  - The origins of the breakdown of Bleaney's theory of magnetic anisotropy are
      described, based on an analysis of eleven different complexes of the second half
      of the 4f elements that form isostructural series. An examination of the chemical
      shift and relaxation rate behaviour of resonances located at least four bonds
      away from the paramagnetic centre was undertaken, and correlated to theoretical
      predictions. The key limitations relate to comparability of ligand field
      splitting with spin-orbit coupling, variation in the position of the principal
      magnetic axis between Ln complexes and the importance of multipolar terms in
      describing lanthanide ligand field interactions.

PMID- 29449917
TI  - Strain discrimination of Yersinia pestis using a SERS-based electrochemically
      driven melting curve analysis of variable number tandem repeat sequences.
AB  - Strain discrimination within genetically highly similar bacteria is critical for
      epidemiological studies and forensic applications. An electrochemically driven
      melting curve analysis monitored by SERS has been utilised to reliably
      discriminate strains of the bacterial pathogen Yersinia pestis, the causative
      agent of plague. DNA amplicons containing Variable Number Tandem Repeats (VNTRs)
      were generated from three strains of Y. pestis: CO92, Harbin 35 and Kim. These
      amplicons contained a 10 base pair VNTR repeated 6, 5, and 4 times in CO92,
      Harbin 35 and Kim respectively. The assay also included a blocker oligonucleotide
      comprising 3 repeats of the 10-mer VNTR sequence. The use of the blocker reduced
      the effective length of the target sequence available to bind to the surface
      bound probe and significantly improved the sensitivity of the discrimination. The
      results were consistent during three replicates that were carried out on
      different days, using different batches of PCR product and different SERS sphere
      segment void (SSV) substrate. This methodology which combines low cost, speed and
      sensitivity is a promising alternative to the time consuming current
      electrophoretic methods.

PMID- 29449918
TI  - What can NMR spectroscopy of selenoureas and phosphinidenes teach us about the pi
      accepting abilities of N-heterocyclic carbenes?
AB  - The electronic nature of the interaction of NHCs with metal centres is of
      interest when exploring their properties, how these properties influence those of
      metal complexes, and how these properties might depend on ligand structure.
      Selenourea and phosphinidene complexes have been proposed to allow the
      measurement of the pi-accepting ability of NHCs, independent of their sigma
      donating ability, via the collection of 77Se or 31P NMR spectra, respectively.
      Herein, the synthesis and characterisation of selenoureas derived from a range of
      imidazol-2-ylidenes, 4,5-dihydroimidazol-2-ylidenes and triazol-2-ylidenes are
      documented. Computational studies are used to explore the link between the
      shielding of the selenium centre and the electronic properties of the NHCs.
      Results show that deltaSe is correlated to the energy gap between a filled lone
      pair orbital on Se and the empty pi* orbital corresponding to the Se-NHC bond.
      Bond energy decomposition analysis indicated no correlation between the orbital
      sigma-contribution to bonding and the chemical shielding, while a good
      correlation was found between the pi-contribution to bonding and the chemical
      shielding, confirming that this technique is indeed able to quantify the ability
      of NHCs to accept pi-electron density. Calculations conducted on phosphinidene
      adducts yielded similar results. With the link between deltaSe and deltaP and pi
      back bonding ability clearly established, these compounds represent useful ways
      in which to fully understand and quantify this aspect of the electronic
      properties of NHCs.

PMID- 29449919
TI  - Rh(iii)-catalyzed C-H olefination of N-pentafluoroaryl benzamides using air as
      the sole oxidant.
AB  - The oxidative olefination of a broad array of arenes and heteroarenes with a
      variety of activated and unactivated olefins has be achieved via a rhodium(iii)
      catalyzed C-H activation reaction. The use of an N-pentafluorophenyl benzamide
      directing group is crucial for achieving catalytic turnovers in the presence of
      air as the sole oxidant without using a co-oxidant.

PMID- 29449920
TI  - A family of N-heterocyclic carbene-stabilized borenium ions for metal-free imine
      hydrogenation catalysis.
AB  - This manuscript probes the steric and electronic attributes that lead to
      "frustrated Lewis pair" (FLP)-type catalysis of imine hydrogenation by borenium
      ions. Hydride abstraction from (ItBu)HB(C6F5)22 prompts intramolecular C-H bond
      activation to give (CHN)2(tBu) (CMe2CH2)CB(C6F5)23, defining an upper limit of
      Lewis acidity for FLP hydrogenation catalysis. A series of seven N-heterocyclic
      carbene-borane (NHC-borane) adducts ((R'CNR)2C)(HBC8H14) (R' = H, R = dipp 4a,
      Mes 5a, Me 8a; R = Me R' = Me 9a, Cl, 10a) and ((HC)2(NMe)(NR)C)(HBC8H14) (R =
      tBu, 6a, Ph 7a) are prepared and converted to corresponding borenium salts. These
      species are evaluated as catalysts for metal-free imine hydrogenation at room
      temperature. Systematic tuning of the carbene donor for the hydrogenation of
      archetypal substrate N-benzylidene-tert-butylamine achieves the highest reported
      turn-over frequencies for FLP-catalyzed hydrogenation at amongst the lowest
      reported catalyst loadings. The most active NHC-borenium catalyst of this series,
      derived from 10a, is readily isolable, crystallographically characterized and
      shown to be effective in the hydrogenation catalysis of functional group
      containing imines and N-heterocycles.

PMID- 29449921
TI  - HMGB1 bound to cisplatin-DNA adducts undergoes extensive acetylation and
      phosphorylation in vivo.
AB  - Cisplatin, one of the most effective anticancer drugs, is a DNA-damaging agent
      that induces cell death primarily by apoptosis. For many years, HMGB1 has been
      known to be a recognition protein for cisplatin-DNA lesions. Here, an application
      of a biomolecular probe based on a peptide-oligonucleotide conjugate is presented
      as a novel method for investigating this recognition process in vivo. Proteins
      known to be involved in the recognition of cisplatin-damaged DNA were pulled down
      and identified, including members of the HMGB family and a number of other
      proteins. Interestingly, at least 4 subforms of HMGB1 bind to cisplatin-DNA
      adducts. These proteins were further identified as post-translationally
      acetylated or phosphorylated forms of HMGB1. These results provide a rich pool of
      protein candidates whose roles in the mechanism of action of platinum drugs
      should be explored. These newly discovered molecular components of the DNA damage
      signalling cascade could serve as novel links between the initial cell responses
      to DNA damage and the downstream apoptotic or DNA repair pathways.

PMID- 29449922
TI  - Bypassing the lack of reactivity of endo-substituted norbornenes with the
      catalytic rectification-insertion mechanism.
AB  - The catalytic 1,2-insertion polymerization of polar norbornenes (NBEs) leads to
      the formation of functional rigid macromolecules with exceptional thermal,
      optical and mechanical properties. However, this remarkable reaction is plagued
      by the low reactivity of the polar monomers, and most notably of those bearing a
      functional group in endo position. We have examined the polymerization mechanism
      of NBEs bearing one or two CO2Me groups either in exo or endo position catalyzed
      by the so-called naked allyl Pd+ SbF6- catalyst (1). Although endo dimethyl ester
      of 5-norbornene-2,3-dicarboxylic acid (NBE(CO2Me)2) is polymerized by 1, two endo
      units are never inserted consecutively along the polymer chain. Indeed, 1 is a
      tandem catalyst which not only catalyzes the insertion of the monomer but also
      the isomerization of endo and exo isomers. Thus, the polymerization of endo
      monomers proceeds via a novel mechanism, coined rectification-insertion
      mechanism, whereby half of the endo monomers are rectified into exo ones prior
      insertion, leading to the formation of an alternating endo-exo copolymer using an
      endo only feedstock. With this mechanism, the lack of reactivity of endo
      norbornenes is bypassed, and the polymerization of predominantly endo polar NBEs
      bearing a variety of functionalities such as esters, imides, acids, aldehydes,
      alcohols, anhydrides, or alkyl bromides proceeds with catalyst loadings as low as
      0.002 mol%.

PMID- 29449923
TI  - Photoinduced dynamics of a cyanine dye: parallel pathways of non-radiative
      deactivation involving multiple excited-state twisted transients.
AB  - Cyanine dyes are broadly used for fluorescence imaging and other photonic
      applications. 3,3'-Diethylthiacyanine (THIA) is a cyanine dye composed of two
      identical aromatic heterocyclic moieties linked with a single methine, -CH
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      torsional degrees of freedom around the methine bonds provide routes for non
      radiative decay, responsible for the inherently low fluorescence quantum yields.
      Using transient absorption spectroscopy, we determined that upon photoexcitation,
      the excited state relaxes along two parallel pathways producing three excited
      state transients that undergo internal conversion to the ground state. The media
      viscosity impedes the molecular modes of ring rotation and preferentially affects
      one of the pathways of non-radiative decay, exerting a dominant effect on the
      emission properties of THIA. Concurrently, the polarity affects the energy of the
      transients involved in the decay pathways and further modulates the kinetics of
      non-radiative deactivation.

PMID- 29449924
TI  - Impacts of gold nanoparticle charge and ligand type on surface binding and
      toxicity to Gram-negative and Gram-positive bacteria.
AB  - Although nanomaterials facilitate significant technological advancement in our
      society, their potential impacts on the environment are yet to be fully
      understood. In this study, two environmentally relevant bacteria, Shewanella
      oneidensis and Bacillus subtilis, have been used as model organisms to elucidate
      the molecular interactions between these bacterial classes and Au nanoparticles
      (AuNPs) with well-controlled and well-characterized surface chemistries: anionic
      3-mercaptopropionic acid (MPA), cationic 3-mercaptopropylamine (MPNH2), and the
      cationic polyelectrolyte poly(allylamine hydrochloride) (PAH). The data
      demonstrate that cationic, especially polyelectrolyte-wrapped AuNPs, were more
      toxic to both the Gram-negative and Gram-positive bacteria. The levels of
      toxicity observed were closely related to the percentage of cells with AuNPs
      associated with the cell surface as measured in situ using flow cytometry. The NP
      concentration-dependent binding profiles were drastically different for the two
      bacteria strains, suggesting the critical role of bacterial cell surface
      chemistry in determining nanoparticle association, and thereby, biological
      impact.

PMID- 29449925
TI  - Redox reaction induced Ostwald ripening for size- and shape-focusing of palladium
      nanocrystals.
AB  - We report here that size- and shape-focusing can be achieved through the well
      known Ostwald ripening process to produce high-quality metal nanocrystals (NCs).
      Using Pd as an example, we show that the addition of small NCs of appropriate
      sizes could help in modulating the growth of larger NCs and enable excellent
      control over both the size and shape uniformity of the products. A detailed
      mechanistic study showed that the self-focusing of Pd NCs relied on a dissolution
      and regrowth process induced by redox reaction of HCHO. With the assistance of
      HCHO, injection of small sacrificial nanocrystals (SNCs), with sizes below a
      critical value, into larger seeds results in the dissolution of the SNCs and
      subsequent deposition onto the larger ones, thus allowing the formation of
      monodisperse Pd NCs. We have identified the critical radius of the SNCs to be
      ~5.7 nm for Pd, and verified that SNCs with sizes larger than that could not
      effectively support the growth of larger seeds. More interestingly, since Ostwald
      ripening involves matter relocation, this synthetic approach could even break the
      self-termination growth habits of metal NCs and produce nanocrystals with sizes
      that are not conveniently accessible by direct growth.

PMID- 29449927
TI  - Unstrained C-C bond activation and directed fluorination through
      photocatalytically-generated radical cations.
AB  - Expanding the repertoire of controlled radical fluorination techniques, we
      present a photosensitized unstrained C-C bond activation/directed
      monofluorination method using Selectfluor and 9-fluorenone. The reaction is
      amenable to the opening of multiple 1-acetal-2-aryl substituted rings to yield
      omega-fluoro carboxylic acids, esters, alcohols, and ketones with relative ease.
      Initial mechanistic insight suggests radical ion intermediates.

PMID- 29449926
TI  - Facet selectivity in gold binding peptides: exploiting interfacial water
      structure.
AB  - Peptide sequences that can discriminate between gold facets under aqueous
      conditions offer a promising route to control the growth and organisation of
      biomimetically-synthesised gold nanoparticles. Knowledge of the interplay between
      sequence, conformations and interfacial properties is essential for predictable
      manipulation of these biointerfaces, but the structural connections between a
      given peptide sequence and its binding affinity remain unclear, impeding
      practical advances in the field. These structural insights, at atomic-scale
      resolution, are not easily accessed with experimental approaches, but can be
      delivered via molecular simulation. A current unmet challenge lies in forging
      links between predicted adsorption free energies derived from enhanced sampling
      simulations with the conformational ensemble of the peptide and the water
      structure at the surface. To meet this challenge, here we use an in situ
      combination of Replica Exchange with Solute Tempering with Metadynamics
      simulations to predict the adsorption free energy of a gold-binding peptide
      sequence, AuBP1, at the aqueous Au(111), Au(100)(1 * 1) and Au(100)(5 * 1)
      interfaces. We find adsorption to the Au(111) surface is stronger than to
      Au(100), irrespective of the reconstruction status of the latter. Our predicted
      free energies agree with experiment, and correlate with trends in interfacial
      water structuring. For gold, surface hydration is predicted as a chief
      determining factor in peptide-surface recognition. Our findings can be used to
      suggest how shaped seed-nanocrystals of Au, in partnership with AuBP1, could be
      used to control AuNP nanoparticle morphology.

PMID- 29449928
TI  - Fluorine teams up with water to restore inhibitor activity to mutant BPTI.
AB  - Introducing fluorine into molecules has a wide range of effects on their
      physicochemical properties, often desirable but in most cases unpredictable. The
      fluorine atom imparts the C-F bond with low polarizability and high polarity, and
      significantly affects the behavior of neighboring functional groups, in a
      covalent or noncovalent manner. Here, we report that fluorine, present in the
      form of a single fluoroalkyl amino acid side chain in the P1 position of the well
      characterized serine-protease inhibitor BPTI, can fully restore inhibitor
      activity to a mutant that contains the corresponding hydrocarbon side chain at
      the same site. High resolution crystal structures were obtained for four BPTI
      variants in complex with bovine beta-trypsin, revealing changes in the
      stoichiometry and dynamics of water molecules in the S1 subsite. These results
      demonstrate that the introduction of fluorine into a protein environment can
      result in "chemical complementation" that has a significantly favorable impact on
      protein-protein interactions.

PMID- 29449929
TI  - Vibrational properties and bonding nature of Sb2Se3 and their implications for
      chalcogenide materials.
AB  - Antimony selenide (antimonselite, Sb2Se3) is a versatile functional material with
      emerging applications in solar cells. It also provides an intriguing prototype to
      study different modes of bonding in solid chalcogenides, all within one crystal
      structure. In this study, we unravel the complex bonding nature of crystalline
      Sb2Se3 by using an orbital-based descriptor (the crystal orbital Hamilton
      population, COHP) and by analysing phonon properties and interatomic force
      constants. We find particularly interesting behaviour for the medium-range
      Sb...Se contacts, which still contribute significant stabilisation but are much
      softer than the "traditional" covalent bonds. These results have implications for
      the assembly of Sb2Se3 nanostructures, and bond-projected force constants appear
      as a useful microscopic descriptor for investigating a larger number of
      chalcogenide functional materials in the future.

PMID- 29449930
TI  - Overcoming aggregation in indium salen catalysts for isoselective lactide
      polymerization.
AB  - A methodology for controlling aggregation in highly active and isoselective
      indium catalysts for the ring opening polymerization of racemic lactide is
      reported. A series of racemic and enantiopure dinuclear indium ethoxide complexes
      bearing salen ligands [(ONNOR)InOEt]2 (R = Br, Me, admantyl, cumyl, t-Bu) were
      synthesized and fully characterized. Mononuclear analogues (ONNOR)InOCH2Pyr (R =
      Br, t-Bu, SiPh3) were synthesized by controlling aggregation with the use of
      chelating 2-pyridinemethoxide functionality. The nuclearity of metal complexes
      was confirmed using PGSE NMR spectroscopy. Detailed kinetic studies show a clear
      initiation period for these dinuclear catalysts, which is lacking in their
      mononuclear analogues. The polymerization behavior of analogous dinuclear and
      mononuclear compounds is identical and consistent with a mononuclear propagating
      species. The isotacticity of the resulting polymers was investigated using direct
      integration and peak deconvolution methodologies and the two were compared.

PMID- 29449931
TI  - Coordination diversity in hydrogen-bonded homoleptic fluoride-alcohol complexes
      modulates reactivity.
AB  - The nucleophilic reactivity of fluoride ion is altered in the presence of
      hydrogen-bond donors, including alcohols. Relatively little is known about the
      coordination involved; to rectify this, the X-ray structures of fourteen novel
      fluoride-alcohol complexes with tetrabutylammonium as the counterion have been
      determined. The coordination number varies from two to four depending on the
      steric bulk of the alcohol and is closely linked to trends in reactivity. This
      diversity in coordination stoichiometry is unprecedented but significant, as it
      implies differences in the ability of the fluoride-alcohol complexes to
      dissociate in solution with release of a more active and/or selective fluoride
      source.

PMID- 29449932
TI  - Engineering beta-sheets employing N-methylated heterochiral amino acids.
AB  - There is a lack of functional group diversity in the reverse turn motifs
      nucleating a beta-sheet conformation in designed peptides, proteins and
      foldamers. The majority of these sequences consist of d-Pro-l-Pro, d-Pro-Gly or
      Asn-Gly as the turn inducing motif restricting their biological application and
      physicochemical modulation. In this report, for the first time we elucidate that
      N-methylation of heterochiral amino acids in linear peptides nucleates beta-sheet
      conformation without the necessity of having a ring or covalent constraint at the
      reverse turn. Our results show that d-Pro can be conveniently substituted by any
      other N-methylated d-amino acid followed by an N-methylated l-amino acid or
      sarcosine to adopt a betaII' turn inducing the beta-sheet folding. Furthermore,
      we reveal that a single amino acid either at the i + 1 or i + 2 site of the
      reverse turn can modulate the right-handed twist, which eventually dictates the
      extent of the foldedness of the beta-hairpin.

PMID- 29449934
TI  - A thin multifunctional coating on a separator improves the cyclability and safety
      of lithium sulfur batteries.
AB  - Lithium-sulfur batteries are one of the most promising next-generation batteries
      due to their high theoretical specific capacity, but are impeded by the low
      utilization of insulating sulfur, unstable morphology of the lithium metal anode,
      and transport of soluble polysulfides. Here, by coating a layer of nano titanium
      dioxide and carbon black onto a commercial polypropylene separator, we
      demonstrate a new composite separator that can confine the polysulfides on the
      cathode side, forming a catholyte chamber, and at the same time block the
      dendritic lithium on the anode side. Lithium-sulfur batteries using this
      separator show a high initial capacity of 1206 mA h g-1 and a low capacity decay
      rate of 0.1% per cycle at 0.5C. Analyses reveal the electrocatalytic effect and
      the excellent dendrite-blocking capability of the ~7 um thick coating.

PMID- 29449933
TI  - A simplified characterization of S-adenosyl-l-methionine-consuming enzymes with 1
      Step EZ-MTase: a universal and straightforward coupled-assay for in vitro and in
      vivo setting.
AB  - Methyltransferases use S-adenosyl-l-methionine (SAM) to deposit methyl marks.
      Many of these epigenetic 'writers' are associated with gene regulation. As cancer
      etiology is highly correlated with misregulated methylation patterns,
      methyltransferases are emerging therapeutic targets. Successful assignment of
      methyltransferases' roles within intricate biological networks relies on (1) the
      access to enzyme mechanistic insights and (2) the efficient screening of chemical
      probes against these targets. To characterize methyltransferases in vitro and in
      vivo, we report a highly-sensitive one-step deaminase-linked continuous assay
      where the S-adenosyl-l-homocysteine (SAH) enzyme-product is rapidly and
      quantitatively catabolized to S-inosyl-l-homocysteine (SIH). To highlight the
      broad capabilities of this assay, we established enzymatic characteristics of two
      protein arginine methyltransferases (PRMT5 and PRMT7), a histone-lysine N
      methyltransferase (DIM-5) and a sarcosine/dimethylglycine N-methyltransferase
      (SDMT). Since the coupling deaminase TM0936 displays robust activity over a broad
      pH-range we determined the pH dependence of SDMT reaction rates. TM0936 reactions
      are monitored at 263 nm, so a drawback may arise when methyl acceptor substrates
      absorb within this UV-range. To overcome this limitation, we used an isosteric
      fluorescent SAM-analog: S-8-aza-adenosyl-l-methionine. Most enzymes tolerated
      this probe and sustained methyltransfers were efficiently monitored through loss
      of fluorescence at 360 nm. Unlike discontinuous radioactive- and antibody-based
      assays, our assay provides a simple, versatile and affordable approach towards
      the characterization of methyltransferases. Supported by three logs of linear
      dynamic range, the 1-Step EZ-MTase can detect methylation rates as low as 2 MUM h
      1, thus making it possible to quantify low nanomolar concentrations of glycine N
      methyltransferase within crude biological samples. With Z'-factors above 0.75,
      this assay is well suited to high-throughput screening and may promote the
      identification of novel therapeutics.

PMID- 29449935
TI  - Pleomorphic liposarcoma of bone: a rare primary malignant bone tumour.
AB  - Background: Liposarcoma is an extremely rare primary bone sarcoma. Case
      presentation: We report a case of primary pleomorphic liposarcoma that arose in
      an 18 year old male in the metaphysis of the left tibia. Plain radiographs showed
      a partly sclerotic lesion and MR imaging a heterogeneous tumour predominantly
      isointense on T1- and high-signal on T2-weighted sequences with focal areas of
      increased T1 signal that suppressed with fat saturation. PET/CT showed marked FDG
      uptake (SUV = 17.1) in the primary tumour as well as a metastasis in the right
      distal femur and multiple small pulmonary metastases. Histologically, the tumour
      was a pleomorphic liposarcoma containing large tumour cells with vacuolated
      cytoplasm and hyperchromatic pleomorphic nuclei as well as numerous lipoblasts
      and scattered brown fat-like cells. Tumour cells strongly expressed FABP4/aP2, a
      marker of adipocyte differentiation, and UCP1, a marker of brown fat, but not
      S100. The case was treated with neoadjuvant MAP chemotherapy, resulting in
      extensive (> 95%) necrosis in the primary tumour and almost complete resolution
      of the femoral and pulmonary metastases. Conclusions: Pleomorphic liposarcoma can
      present as a sclerotic primary malignant bone tumour; markers of adipose
      differentiation are useful in histological diagnosis and neoadjuvant MAP
      chemotherapy results in significant tumor necrosis.

PMID- 29449937
TI  - Thermal decomposition of the amino acids glycine, cysteine, aspartic acid,
      asparagine, glutamic acid, glutamine, arginine and histidine.
AB  - Background: The pathways of thermal instability of amino acids have been unknown.
      New mass spectrometric data allow unequivocal quantitative identification of the
      decomposition products. Results: Calorimetry, thermogravimetry and mass
      spectrometry were used to follow the thermal decomposition of the eight amino
      acids G, C, D, N, E, Q, R and H between 185  degrees C and 280  degrees C.
      Endothermic heats of decomposition between 72 and 151 kJ/mol are needed to form
      12 to 70% volatile products. This process is neither melting nor sublimation.
      With exception of cysteine they emit mainly H2O, some NH3 and no CO2. Cysteine
      produces CO2 and little else. The reactions are described by polynomials, AA->a
      NH3+b H2O+c CO2+d H2S+e residue, with integer or half integer coefficients. The
      solid monomolecular residues are rich in peptide bonds. Conclusions: Eight of the
      20 standard amino acids decompose at well-defined, characteristic temperatures,
      in contrast to commonly accepted knowledge. Products of decomposition are simple.
      The novel quantitative results emphasize the impact of water and cyclic
      condensates with peptide bonds and put constraints on hypotheses of the origin,
      state and stability of amino acids in the range between 200  degrees C and 300 
      degrees C.

PMID- 29449936
TI  - Function of aquaporins in sepsis: a systematic review.
AB  - Background: Sepsis is a common cause of death in intensive care units worldwide.
      Due to the high complexity of this immunological syndrome development of novel
      therapeutic strategies is urgent. Promising drug targets or biomarkers may depict
      aquaporins (AQPs) as they regulate crucial key mechanisms of sepsis. Main body:
      Here we report on base of the current literature that several AQPs are involved
      in different physiological processes of sepsis. In immune system mainly AQPs 3, 5
      and 9 seem to be important, as they regulate the migration of different immune
      cells. Several studies showed that AQP3 is essential for T cell function and
      macrophage migration and that AQP5 and AQP9 regulate neutrophil cell migration
      and impact sepsis survival. Additionally, to the function in immune system AQPs 1
      and 5 play a role in sepsis induced lung injury and their downregulation after
      inflammatory stimuli impair lung injury. By contrast, AQP4 expression is up
      regulated during brain inflammation and aggravates brain edema in sepsis. In
      kidney AQP2 expression is downregulated during sepsis and can cause renal
      failure. Some studies also suggest a role of AQP1 in cardiac function.
      Conclusion: In conclusion, AQPs are involved in many physiological dysfunctions
      in sepsis and their expressions are differently regulated. Additional research on
      the regulatory mechanisms of aquaporins may identify potential therapeutic
      targets.

PMID- 29449939
TI  - Innovative approaches to genome editing in avian species.
AB  - The tools available for genome engineering have significantly improved over the
      last 5 years, allowing scientist to make precise edits to the genome. Along with
      the development of these new genome editing tools has come advancements in
      technologies used to deliver them. In mammals genome engineering tools are
      typically delivered into in vitro fertilized single cell embryos which are
      subsequently cultured and then implanted into a recipient animal. In avian
      species this is not possible, so other methods have been developed for genome
      engineering in birds. The most common involves in vitro culturing of primordial
      germ cells (PGCs), which are cells that migrate through the embryonic circulatory
      system to the developing gonad and colonize the gonad, eventually differentiating
      into the gonadocytes which produce either sperm or ova. While in culture the PGCs
      can be modified to carry novel transgenes or gene edits, the population can be
      screened and enriched, and then transferred into a recipient embryo. The largest
      drawback of PGC culture is that culture methods do not transfer well across avian
      species, thus there are reliable culture methods for only a few species including
      the chicken. Two newer technologies that appear to be more easily adapted in a
      wider range of avian species are direct injection and sperm transfection assisted
      gene editing (STAGE). The direct injection method involves injecting genome
      engineering tools into the circulatory system of the developing embryo just prior
      to the developmental time point when the PGCs are migrating to the gonads. The
      genome engineering tools are complexed with transfection reagents, allowing for
      in vivo transfection of the PGCs. STAGE utilizes sperm transfection to deliver
      genome engineering tools directly to the newly fertilized embryo. Preliminary
      evidence indicates that both methodologies have the potential to be adapted for
      use in birds species other than the chicken, however further work is needed in
      this area.

PMID- 29449938
TI  - Molecular characteristics and successful management of a respiratory syncytial
      virus outbreak among pediatric patients with hemato-oncological disease.
AB  - Background: Respiratory syncytial virus (RSV) is responsible for upper and lower
      respiratory tract infection in adults and children. Especially immunocompromised
      patients are at high risk for a severe course of infection, and mortality is
      increased. Moreover RSV can spread in healthcare settings and can cause
      outbreaks. Herein we demonstrate the successful control and characteristics of a
      RSV outbreak that included 8 patients in our Department of Pediatric Hematology
      and Oncology. Methods: We performed an epidemiologic investigation and a
      molecular analysis of the outbreak strains. Moreover we present the outbreak
      control bundle and our concept for RSV screening in the winter season. Results:
      RSV A and B strains caused the outbreak. RSV B strains affected 3 patients, 2 of
      whom were co-infected with RSV A. Exactly this RSV A strain was detected in
      another 5 patients. Our multimodal infection control bundle including
      prophylactic RSV screening was able to rapidly stop the outbreak. Conclusion: An
      infection control bundle in RSV outbreaks should address all potential
      transmission pathways. In pediatric settings the restriction of social activities
      might have a temporal negative impact on quality of life but helps to limit
      transmission opportunities. Molecular analysis allows better understanding of RSV
      outbreaks and, if done in a timely manner, might be helpful for guidance of
      infection control measures.

PMID- 29449940
TI  - Effects of fumaric acid supplementation on methane production and rumen
      fermentation in goats fed diets varying in forage and concentrate particle size.
AB  - Background: In rumen fermentation, fumaric acid (FA) could competitively utilize
      hydrogen with methanogenesis to enhance propionate production and suppress
      methane emission, but both effects were diet-dependent. This study aimed to
      explore the effects of FA supplementation on methanogenesis and rumen
      fermentation in goats fed diets varying in forage and concentrate particle size.
      Methods: Four rumen-cannulated goats were used in a 4 * 4 Latin square design
      with a 2 * 2 factorial arrangement of treatments: low or high ratio of forage
      particle size: concentrate particle size (Fps:Cps), without or with FA
      supplementation (24 g/d). Fps:Cps was higher in the diet with chopped alfalfa hay
      plus ground corn than in that with ground alfalfa hay plus crushed corn. Results:
      Both increasing dietary Fps:Cps and FA supplementation shifted ruminal volatile
      fatty acid (VFA) patterns toward more propionate and less acetate in goats. An
      interaction between dietary Fps:Cps and FA supplementation was observed for the
      ratio of acetate to propionate (A:P), which was more predominant when FA was
      supplemented in the low-Fps:Cps diet. Methane production was reduced by FA, and
      the reduction was larger in the low-Fps:Cps diet (31.72%) than in the high
      Fps:Cps diet (17.91%). Fumaric acid decreased ruminal total VFA concentration and
      increased ruminal pH. No difference was found in ruminal DM degradation of
      concentrate or alfalfa hay by dietary Fps:Cps or FA. Goats presented a lower
      ruminal methanogen abundance with FA supplementation and a higher B. fibrisolvens
      abundance with high dietary Fps:Cps. Conclusions: Adjusting dietary Fps:Cps is an
      alternative dietary model for studying diet-dependent effects without changing
      dietary chemical composition. Fumaric acid supplementation in the low-Fps:Cps
      diet showed greater responses in methane mitigation and propionate increase.

PMID- 29449941
TI  - Cardiovascular risk factor burden in Africa and the Middle East across country
      income categories: a post hoc analysis of the cross-sectional Africa Middle East
      Cardiovascular Epidemiological (ACE) study.
AB  - Background: A significant number of cardiovascular disease (CVD)-related deaths
      occur in developing countries. An increasing prevalence of CVD is associated with
      a change in the macro-economy of these countries. In this post hoc analysis, CVD
      risk factor (CVDRF) prevalence is evaluated across countries based on national
      income in the Africa and Middle East Region (AfME). Methods: Data from the Africa
      Middle East Cardiovascular Epidemiological (ACE) study were used; a cross
      sectional study in 14 AfME countries (94 clinics) from July 2011-April 2012,
      which evaluated CVDRF prevalence in stable adult outpatients. World Bank
      definitions were used to classify countries as low-income (LI), lower-middle
      income (LMI), upper-middle-income (UMI) or high-income (HI) countries. Four
      thousand three hundred seventy-eight subjects were recruited where 260 (6%), 1324
      (30%), 1509 (35%) and 1285 (29%) were from LI, LMI, UMI, and HI countries,
      respectively. Results: Of all the CVDRFs evaluated, almost two-thirds of the
      study population across the national income groups had abdominal obesity and
      dyslipidemia. Countries in the HI category were associated with a higher
      prevalence of diabetes (32%), obesity (44%) and smoking (16%). UMI and HI
      countries were associated with higher clustering of CVDRFs where at least one
      third of subjects having four or more CVDRFs. Lower income countries had lower
      blood pressure control rates and lower percentages of outpatients achieving LDL
      cholesterol targets. Conclusion: The burden of CVDRFs in stable outpatients is
      high across the national income categories in the AfME region, with HI countries
      showing a higher prevalence of CVDRFs. The high burden in lower income countries
      is associated with sub-optimal control of dyslipidemia and hypertension. Lowering
      the CVDRF burden would need specific public health actions in line with positive
      changes in the macro-economy of these countries. Trial registration: The ACE
      trial is registered under NCT01243138.

PMID- 29449942
TI  - Epidemic potential by sexual activity distributions.
AB  - For sexually transmitted infections like HIV to propagate through a population,
      there must be a path linking susceptible cases to currently infectious cases. The
      existence of such paths depends in part on the degree distribution. Here, we use
      simulation methods to examine how two features of the degree distribution affect
      network connectivity: Mean degree captures a volume dimension, while the skewness
      of the upper tail captures a shape dimension. We find a clear interaction between
      shape and volume: When mean degree is low, connectivity is greater for long
      tailed distributions, but at higher mean degree, connectivity is greater in short
      tailed distributions. The phase transition to a giant component and giant
      bicomponent emerges as a positive function of volume, but it rises more sharply
      and ultimately reaches more people in short-tail distributions than in long-tail
      distributions. These findings suggest that any interventions should be attuned to
      how practices affect both the volume and shape of the degree distribution, noting
      potential unanticipated effects. For example, policies that primarily affect high
      volume nodes may not be effective if they simply redistribute volume among lower
      degree actors, which appears to exacerbate underlying network connectivity.

PMID- 29449943
TI  - Aging-like physiological changes in the skin of Japanese obese diabetic patients.
AB  - Objective: Obesity-associated diabetes causes aging-like changes to skin
      physiology in animal models, but there have been no clinical studies focusing on
      human obese diabetic patients. The purpose of this study was to examine the
      hypothesis that obesity-associated diabetes accelerates aging-like skin changes
      in Japanese people. Methods: This cross-sectional study enrolled obese-diabetes
      patients (body mass index >= 25 kg m-2) and healthy volunteers (body mass index <
      25 kg m-2) as controls. Skin physiology parameters relating to aging (stratum
      corneum hydration, transepidermal water loss, skin pH, advanced glycation end
      products, and dermal collagen density) were evaluated in the two groups. Results:
      About 37 subjects participated (16 in a control group and 21 in an obese-diabetes
      group). Age was not significantly different between the groups. The stratum
      corneum hydration level was significantly lower in the obese-diabetes group.
      Transepidermal water loss and levels of advanced glycation end-products were
      significantly higher in this group. Skin pH was not significantly different
      between groups. Dermal collagen density decreased in the obese-diabetes group.
      Conclusion: We showed that obese-diabetes patients have decreased stratum corneum
      hydration, increased transepidermal water loss, higher skin advanced glycation
      end-products and decreased dermal collagen fiber density compared with normal
      weight subjects. These results indicate that the ordinary age-related
      physiological skin changes seen in the elderly can also occur in obese-diabetes
      patients aged in their 40s.

PMID- 29449944
TI  - Dexmedetomidine use during epiduroscopy reduces fentanyl use and postoperative
      nausea and vomiting: A single-center retrospective study.
AB  - Objectives: Minimally invasive epiduroscopy has recently been reported as an
      effective treatment procedure for chronic and intractable low back pain. However,
      no study has determined safe anesthetics for monitored anesthesia care during
      epiduroscopy. We aimed to compare and evaluate conventional monitored anesthesia
      care drugs with dexmedetomidine. Methods: A retrospective study including all
      patients who underwent epiduroscopy at the JR Tokyo General Hospital from April
      2011 to March 2016 was designed. The epiduroscopy procedures were performed under
      anesthesia with dexmedetomidine plus fentanyl (dexmedetomidine group) or
      droperidol plus fentanyl (neuroleptanalgesia group). Patients who received
      analgesics other than fentanyl, another analgesic combined with fentanyl, any
      sedative other than dexmedetomidine or droperidol, or who had incomplete data
      were excluded. We compared (1) the type and dose of medication during the
      epiduroscopy and (2) the incidence of postoperative nausea and vomiting. Results:
      We identified 45 patients (31 and 14 in the dexmedetomidine and
      neuroleptanalgesia groups, respectively) with a mean age of 69.0 years. The two
      groups had comparable characteristics, such as age, sex, body mass index, the
      American Society of Anesthesiologists Physical Status, analgesics used in the
      clinic, comorbidities, history of smoking, and the duration of anesthesia. The
      dexmedetomidine group received a significantly lower fentanyl dose during surgery
      (126 +/- 14 vs 193 +/- 21 ug, mean +/- standard deviation, p = 0.014) and
      exhibited a significantly lower incidence of postoperative nausea and vomiting (1
      vs 3, p = 0.047) than the neuroleptanalgesia group. Conclusion: This study
      involved elderly patients, and the use of dexmedetomidine in monitored anesthesia
      care during epiduroscopy procedures in these patients may reduce the required
      fentanyl dose during surgery and the incidence of postoperative nausea and
      vomiting. This strategy may help prevent respiratory depression and aspiration.

PMID- 29449945
TI  - Psychosocial factors associated with change in pain and disability outcomes in
      chronic low back pain patients treated by physiotherapist: A systematic review.
AB  - Background: Almost 80% of people have low back pain at least once in their life.
      Clinical guidelines emphasize the use of conservative physiotherapy and the
      importance of staying active. While the psychological factors predicting poor
      recovery following surgical intervention are understood, the psychosocial factors
      associated with poor outcomes following physiotherapy have yet to be identified.
      Methods: Electronic searches of PubMed, Medline, CINAHL, PsycINFO and EBSCO were
      conducted using terms relating to psychosocial factors, chronic low back pain,
      disability and physiotherapy. Papers examining the relationship between
      psychosocial factors and pain and disability outcomes following physiotherapy
      were included. Two reviewers selected, appraised and extracted studies
      independently. Results: In total, 10 observational studies were identified that
      suggested an association between fear of movement, depression, self-efficacy and
      catastrophizing in modifying pain and disability outcomes following
      physiotherapy. Discussion: Although limited by methodological shortcomings of
      included studies, and heterogeneity of physiotherapy interventions and measures
      of disability and psychosocial outcomes, the findings are consistent with other
      research in the context of back pain and physiotherapy, which suggest an
      association between psychosocial factors, including fear of movement,
      catastrophizing and self-efficacy and pain and disability outcomes in chronic low
      back pain patients treated by physiotherapist. However, a direct relationship
      cannot be concluded from this study. Conclusion: Findings suggest an association
      between psychosocial factors, including fear of movement, catastrophizing and
      self-efficacy and pain and disability outcomes in chronic low back pain patients
      treated by physiotherapist, which warrants further study.

PMID- 29449946
TI  - Prescriber continuity and medication availability in older adults with
      cardiometabolic conditions.
AB  - Background: Many older adults have multiple conditions and see multiple
      providers, which may impact their use of essential medications. Objective: We
      examined whether the number of prescribers of these medications was associated
      with the availability of medications, a surrogate for adherence, to manage
      diabetes, hypertension or dyslipidemia. Methods: A retrospective cohort of
      383,145 older adults with diabetes, hypertension or dyslipidemia in the US
      Medicare program living in 10 states. The association between the number of
      prescribers of cardiometabolic medications in 2010 and medication availability
      (proportion of days with medication on hand) in 2011 was estimated via logistic
      regression, controlling for patient demographic characteristics and chronic
      conditions. Results: Medicare beneficiaries with diabetes, hypertension and/or
      dyslipidemia had an average of five chronic conditions overall, obtained 10-12
      medications for all conditions and most often had one prescriber of
      cardiometabolic medications. In adjusted analyses, the number of prescribers was
      not significantly associated with availability of oral diabetes agents but having
      more prescribers is associated with increased medication availability in older
      Medicare beneficiaries with dyslipidemia or hypertension. Conclusion: The
      incremental addition of new prescribers may be clinically reasonable for complex
      patients but creates the potential for coordination problems and informational
      discontinuity over time. Health systems may want to identify complex patients
      with multiple prescribers to minimize care fragmentation.

PMID- 29449947
TI  - Reversible platypnoea-orthodeoxia syndrome in post-tuberculosis bronchial
      stenosis.
AB  - Bronchial stenosis is known to complicate endobronchial tuberculosis despite
      medical therapy. It is often associated with dyspnoea. In severe cases, bronchial
      stenosis results in airflow obstruction, impaired secretion clearance, and can
      lead to respiratory failure. We present an unusual observation of platypnoea
      orthodeoxia syndrome in a young woman with acute atelectasis due to post
      tuberculosis bronchial stricture. Imaging revealed complete middle and right
      lower lobe atelectasis with a partially aerated right upper lobe. In the sitting
      posture, there was positional worsening of dyspnoea associated with an increase
      in the alveolar-arterial oxygen gradient and shunt fraction. The likely mechanism
      was due to gravitational difference in ventilation-perfusion matching. The
      platypnoea-orthodeoxia syndrome was reversible following balloon dilatation of
      the bronchial stenosis and expansion of the collapsed lung.

PMID- 29449948
TI  - Physical activity and sedentary behavior following pediatric burns - a
      preliminary investigation using objective activity monitoring.
AB  - Background: Adequate levels of regular physical activity (PA) are crucial for
      health and well-being. Pediatric burn injuries can have major physiological
      consequences in both the short and long term. The question is whether these
      consequences affect post burn PA levels. This study therefore aimed to describe
      PA and sedentary behavior (SB) in children and adolescents 1-5 years after burn
      injury. Methods: Daily PA and SB were monitored in 20 children and adolescents
      (12 boys and 8 girls, aged 6-17 years, with burns covering 10-37% of total body
      surface area, 1-5 years post burn) for 1 week using the ActiGraph GTX3+
      accelerometer. Activity counts were categorized into SB, light PA, moderate PA,
      vigorous PA, moderate-to-vigorous PA (MVPA), and total PA. Outcomes were compared
      with non-burned reference values and PA levels recommended by the World Health
      Organization (WHO). Results: The participants spent about 5.1 h per day on total
      PA and 7.4 h on SB. Most of the active time (~ 83%) was categorized as light PA.
      Thirty-five percent of the group, especially the young boys, spent on average >=
      60 min on MVPA per day. The boys, although with large interindividual
      differences, spent more time on MVPA than the girls (p < .005). Older age was
      associated with less PA time, while more time was spent sedentary. No trends were
      found indicating an effect of burn characteristics, time post burn, or length of
      hospital stay, and no differences were found with non-burned peers. Conclusion:
      Duration and intensity of PA and SB in children and adolescents 1-5 years after
      burn injury were similar to non-burned peers. However, only 35% of the group met
      the WHO physical activity recommendation. Given the increased long term risk for
      physical conditions following pediatric burns, physical activity should be
      encouraged in this vulnerable population. Trial registration: The study is
      registered in the National Academic Research and Collaborations Information
      System of the Netherlands (OND1348800).

PMID- 29449949
TI  - British Thoracic Society Guideline for the management of non-tuberculous
      mycobacterial pulmonary disease (NTM-PD).
AB  - The full guideline for the management of non-tuberculous mycobacterial pulmonary
      disease is published in Thorax. The following is a summary of the recommendations
      and good practice points. The sections referred to in the summary refer to the
      full guideline.

PMID- 29449950
TI  - Impact of malnutrition on survival and healthcare utilization in Medicare
      beneficiaries with diabetes: a retrospective cohort analysis.
AB  - Objective: The aim of this study was to examine the impact of pre-existing
      malnutrition on survival and economic implications in elderly patients with
      diabetes. Research design and methods: A retrospective observational study was
      conducted to examine the impact of malnutrition with or without other significant
      health conditions on survival time and healthcare costs using the Centers for
      Medicare and Medicaid Services (CMS) data from 1999 to 2014 for beneficiaries
      with a confirmed first date of initial diagnosis of diabetes (n=15 121 131). The
      primary outcome was survival time, which was analyzed using all available data
      and after propensity score matching. Healthcare utilization cost was a secondary
      outcome. Results: A total of 801 272 beneficiaries were diagnosed with
      malnutrition. The analysis on propensity score-matched data for the effect of
      common conditions on survival showed that the risk for death in beneficiaries
      with diabetes increased by 69% in malnourished versus normo-nourished (HR, 1.69;
      99.9% CI 1.64 to 1.75; P<0.0001) beneficiaries. Malnutrition increased the risk
      for death within each of the common comorbid conditions including ischemic heart
      disease (1.63; 1.58 to 1.68), chronic obstructive pulmonary disorder (1.60; 1.55
      to 1.65), stroke or transient ischemic attack (1.57; 1.53 to 1.62), heart failure
      (1.54; 1.50 to 1.59), chronic kidney disease (1.50; 1.46 to 1.55), and acute
      myocardial infarction (1.47; 1.43 to 1.52). In addition, the annual total
      spending for the malnourished beneficiaries was significantly greater than that
      for the normo-nourished beneficiaries ($36 079 vs 20 787; P<0.0001). Conclusions:
      Malnutrition is a significant comorbidity affecting survival and healthcare costs
      in CMS beneficiaries with diabetes. Evidence-based clinical decision pathways
      need to be developed and implemented for appropriate screening, assessment,
      diagnosis and treatment of malnourished patients, and to prevent malnutrition in
      normo-nourished patients with diabetes.

PMID- 29449951
TI  - Glucagon-like peptide-1 receptor agonists are not associated with retinal adverse
      events in the FDA Adverse Event Reporting System.
AB  - Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely used
      for the treatment of type 2 diabetes. In large trials, the GLP-1RAs liraglutide
      and semaglutide improved cardiovascular outcomes, but semaglutide was associated
      with an increased risk of retinopathy progression. We herein evaluated the
      association between GLP-1RA and retinal adverse events (AE) in the Food and Drug
      Administration Adverse Event Reporting System (FAERS). Research design and
      methods: We mined the FAERS between 2004q1 and 2017q1 (for a total of 9 217 555
      AE reports) to analyze disproportionality and evaluate the association between
      GLP-1RAs and AEs involving the retina. We compared the frequency of retinal AEs
      among reports including GLP-1RAs and in those including other glucose-lowering
      medications (GLMs) as suspect or concomitant drugs. Results: We retrieved 114 814
      reports involving GLP-1RA and 694 725 reports involving other GLMs as suspect or
      concomitant drugs. The cumulative frequency of retinal AEs was 2.53/1000 for
      reports involving GLP-1RA vs 6.62/1000 for reports involving other GLMs, with a
      proportional reporting ratio of 0.38 (95% CI 0.34 to 0.43; P<0.0001). Reports
      involving GLP-1RAs listed significantly more comorbid conditions and concomitant
      medications. Findings were consistent after filtering the diabetes indication
      irrespective of concomitant GLM, in reports including and in those not including
      insulin, and for the various GLP-1RAs. Conclusions: In the FAERS there is no
      evidence that GLP-1RAs are associated with AEs suggestive of retinopathy
      progression. Despite more comorbid conditions and concomitant medications, in
      reports with GLP-1RA the frequency of retinal AEs was significantly lower than in
      reports with other GLMs.

PMID- 29449952
TI  - Variations of dietary intake by glycemic status and Hispanic/Latino heritage in
      the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
AB  - Objective: A healthy diet is important for diabetes prevention and control;
      however, few studies have assessed dietary intake among US Hispanics/Latinos, a
      diverse population with a significant burden of diabetes. To address this gap in
      the literature, we determined intake of energy, macro/micronutrients, and vitamin
      supplements among Hispanics/Latinos by glycemic status and heritage. Research
      design and methods: Cross-sectional study of adults aged 18-74 years from the
      Hispanic Community Health Study/Study of Latinos (2008-2011) with complete
      baseline data on glycemic status and two 24-hour dietary recalls (n=13 089). Age
      adjusted and sex-adjusted and multivariable-adjusted measures of intake were
      determined by glycemic status and heritage. Results: Mean age-adjusted and sex
      adjusted energy intake was significantly lower among Hispanics/Latinos with
      diagnosed diabetes compared with those with normal glycemic status (1665 vs 1873
      kcal, P<0.001). Fiber intake was higher among those with diagnosed diabetes
      versus normal glycemic status (P<0.01). Among those with diagnosed diabetes,
      energy intake was highest among those with Cuban heritage compared with most
      other heritage groups (P<0.01 for all, except Mexicans), but there was no
      difference after additional adjustment. Fiber intake was significantly lower for
      those of Cuban heritage (vs Dominican, Central American, and Mexican), and sodium
      intake was significantly higher (vs all other heritage groups) (P<0.01 for all);
      findings were null after additional adjustment. There was no difference in
      supplemental intake of vitamin D, calcium, magnesium, or potassium by glycemic
      status. Conclusions: As part of the care of Hispanics/Latinos with diabetes,
      attention should be made to fiber and sodium consumption.

PMID- 29449953
TI  - Informing the development of online weight management interventions: a
      qualitative investigation of primary care patient perceptions.
AB  - Background: The internet is a potentially promising medium for delivering weight
      loss interventions. The current study sought to explore factors that might
      influence primary care patients' initial uptake and continued use (up to four
      weeks) of such programmes to help inform the development of novel, or refinement
      of existing, weight management interventions. Methods: Semi-structured interviews
      were conducted with 20 patients purposively sampled based on age, gender and BMI
      from a single rural general practice. The interviews were conducted 4 weeks after
      recruitment at the general practice and focused on experiences with using one of
      three freely available weight loss websites. Thematic Analysis was used to
      analyse the data. Results: Findings suggested that patients were initially
      motivated to engage with internet-based weight loss programmes by their
      accessibility and novelty. However, continued use was influenced by substantial
      facilitators and barriers, such as time and effort involved, reaction to
      prompts/reminders, and usefulness of information. Facilitation by face-to-face
      consultations with the GP was reported to be helpful in supporting change.
      Conclusions: Although primary care patients may not be ready yet to solely depend
      on online interventions for weight loss, their willingness to use them shows
      potential for use alongside face-to-face weight management advice or
      intervention. Recommendations to minimise barriers to engagement are provided.

PMID- 29449954
TI  - Metabotropic glutamate receptor 5 tracer [18F]-FPEB displays increased binding
      potential in postcentral gyrus and cerebellum of male individuals with autism: a
      pilot PET study.
AB  - Background: Autism is a neurodevelopmental disorder that is first manifested
      during early childhood. Postmortem experiments have identified significantly
      elevated expression of metabotropic glutamate receptor 5 (mGluR5) in cerebellar
      vermis and prefrontal cortex of individuals with autism. Methods: In the current
      study we employed the mGluR5 tracer [18F]-3-fluoro-5-[(pyridin-3
      yl)ethynyl]benzonitrile ([18F]-FPEB) to quantify mGluR5 binding in vivo in adults
      with autism vs. healthy controls using positron emission tomography (PET).
      Results: We identified significantly higher [18F]-FPEB binding potential in the
      postcentral gyrus and cerebellum of individuals with autism. There was a
      significant negative correlation between age and [18F]-FPEB binding potential in
      the cerebellum but not in the postcentral gyrus. In the precuneus, [18F]-FPEB
      binding potential correlated positively with the lethargy subscale score for the
      Aberrant Behavioral Checklist (ABC). In cerebellum, there were significant
      negative correlations between [18F]-FPEB binding potential and ABC total score,
      ABC hyperactivity subscale score, and the ABC inappropriate speech subscale
      score. Conclusions: These novel findings demonstrate for the first time that
      mGluR5 binding is altered in critical brain areas of subjects with autism,
      suggesting abnormal glutamate signaling in these regions. Finally, the
      correlations between altered [18F]-FPEB binding potential in the cerebellum and
      precuneus suggest that some autistic symptoms may be influenced by abnormal
      glutamate signaling.

PMID- 29449956
TI  - Bilateral bronchial stent deployment for palliative treatment of a compressive
      intrathoracic mass in a cat.
AB  - Case summary: Bronchial stents may be useful to relieve clinical signs of
      extraluminal compression. Herein we describe a case which, to our knowledge, is
      the first cat where bilateral bronchial stents have been used clinically.
      Respiratory signs of principal bronchial compression were alleviated after the
      stent procedure. Minor complications occurred, specifically: severe hypoxia
      during stent deployment; a transient, self-limiting postoperative pneumothorax
      possibly associated with ventilation-induced lung injury; bronchopneumonia
      (possibly pre-existing); and transient worsening of cough postoperatively. Stents
      were well- tolerated long- term. The cat was euthanased at 44 weeks post-stent
      procedure, owing to clinical signs of regurgitation, seemingly related to
      oesophageal dysfunction associated with tumour invasion. Relevance and novel
      information: In this case, it appeared that bronchial stents were feasible and
      the procedure was associated with long-term improvement in respiratory signs
      related to extraluminal bronchial compression.

PMID- 29449955
TI  - Prospects for Precision Medicine in Glomerulonephritis Treatment.
AB  - Background: Glomerulonephritis (GN) consists of a group of kidney diseases that
      are categorized based on shared histopathological features. The current
      classifications for GN make it difficult to distinguish the individual
      variability in presentation, disease progression, and response to treatment. GN
      is a significant cause of end-stage renal disease (ESRD), and improved therapies
      are desperately needed because current immunosuppressive therapies sometimes lack
      efficacy and can lead to significant toxicities. In recent years, the combination
      of high-throughput genetic approaches and technological advances has identified
      important regulators contributing to GN. Objectives: In this review, we summarize
      recent findings in podocyte biology and advances in experimental approaches that
      have opened the possibility of precision medicine in GN treatment. We provide an
      integrative basic science and clinical overview of new developments in GN
      research and the discovery of potential candidates for targeted therapies in GN.
      Findings: Advances in podocyte biology have identified many candidates for
      therapeutic targets and potential biomarkers of glomerular disease. The goal of
      precision medicine in GN is now being pursued with recent technological
      improvements in genetics, accessibility of biologic and clinical information with
      tissue biobanks, high-throughput analysis of large-scale data sets, and new human
      model systems such as kidney organoids. Conclusion: With advances in data
      collection, technologies, and experimental model systems, we now have vast tools
      available to pursue precision medicine in GN. We anticipate a growing number of
      studies integrating data from high-throughput analysis with the development of
      diagnostic tools and targeted therapies for GN in the near future.

PMID- 29449957
TI  - Early detection of myocardial dysfunction using two-dimensional speckle tracking
      echocardiography in a young cat with hypertrophic cardiomyopathy.
AB  - Case summary: A 5-month-old intact female Scottish Fold cat was presented for
      cardiac evaluation. Careful auscultation detected a slight systolic murmur
      (Levine I/VI). The findings of electrocardiography, thoracic radiography, non
      invasive blood pressure measurements and conventional echocardiographic studies
      were unremarkable. However, two-dimensional speckle tracking echocardiography
      revealed abnormalities in myocardial deformations, including decreased early-to
      late diastolic strain rate ratios in longitudinal, radial and circumferential
      directions, and deteriorated segmental systolic longitudinal strain. At the
      follow-up examinations, the cat exhibited echocardiographic left ventricular
      hypertrophy and was diagnosed with hypertrophic cardiomyopathy using conventional
      echocardiography. Relevance and novel information: This is the first report on
      the use of two-dimensional speckle tracking echocardiography for the early
      detection of myocardial dysfunction in a cat with hypertrophic cardiomyopathy;
      the myocardial dysfunction was detected before the development of hypertrophy.
      The findings from this case suggest that two-dimensional speckle tracking
      echocardiography can be useful for myocardial assessment when conventional
      echocardiographic and Doppler findings are ambiguous.

PMID- 29449958
TI  - A mobile phone-based program to promote healthy behaviors among adults with
      prediabetes: study protocol for a pilot randomized controlled trial.
AB  - Background: Rates of participation in Diabetes Prevention Programs (DPPs) are
      low. This may be due, in part, to low levels of autonomous motivation (i.e.,
      motivation that arises from internal sources and sustains healthy behaviors over
      time) to prevent type 2 diabetes (T2DM) among many individuals with prediabetes.
      Mobile health (mHealth) technologies that incorporate principles from the Self
      Determination Theory offer an effective and scalable approach to increase
      autonomous motivation levels. One promising mobile phone-based application is
      JOOL Health, which aims to help users connect certain health behaviors (e.g.,
      sleep and diet) with personal values in specific life domains (e.g., family and
      work). The first aim of this study is to estimate whether JOOL Health can
      increase autonomous motivation to prevent T2DM among individuals with prediabetes
      who declined DPP participation. The second aim of this pilot study is to examine
      the intervention's feasibility and acceptability. Methods: This is a 12-week,
      three-arm pilot randomized controlled trial. We will recruit 105 individuals with
      prediabetes who did not engage in a DPP despite invitation from their health plan
      to participate in face-to-face or web-based programs at no out-of-pocket-cost.
      Participants will be randomized to one of three study arms: (1) a group that
      receives information on prediabetes, evidence-based strategies to decrease
      progression to T2DM, and a list of resources for mHealth tools for monitoring
      diet, physical activity, and weight (comparison group); (2) a group that receives
      the JOOL Health application; and (3) a group that receives the JOOL Health
      application as well as a Fitbit activity tracker and wireless-enabled scale. Our
      primary outcome is change in autonomous motivation to prevent T2DM (measured
      using the Treatment Self-Regulation Questionnaire). We will also collect data
      related to the intervention's feasibility (recruitment and retention rates) and
      acceptability (adherence and qualitative experience) as well as changes in
      psychosocial outcomes, hemoglobin A1c, and weight. Discussion: To our knowledge,
      this is the first study that aims to promote positive health behaviors among
      individuals with prediabetes who previously declined to participate in a DPP. Our
      results will inform a larger trial to test the effect of JOOL Health on
      clinically relevant outcomes, including weight loss, physical activity, and DPP
      engagement. Trial registration: NCT03025607. Registered February 2017.

PMID- 29449959
TI  - Sulfobetaine methacrylate hydrogel-coated anti-fouling surfaces for implantable
      biomedical devices.
AB  - Background: Zwitterionic molecules have been widely studied as coating materials
      for preparing anti-fouling surfaces because they possess strong hydration
      properties that can resist non-specific protein adsorption. Numerous studies on
      surface modification using zwitterionic molecules have been investigated, such as
      electrochemically mediated and photoinitiated radical polymerization. However,
      these methods have some limitations, including multi-step process, difficulties
      in producing thick and dense layers as well as the requirement of extra
      facilities. In this study, we report a novel zwitterionic hydrogel-coating method
      via Fenton reaction for the preparation of anti-fouling surfaces. Methods:
      Sulfobetaine methacrylate (SBMA) hydrogel was coated on polyurethane (PU) by
      polymerization of SBMA molecules via the Fenton reaction. The coated surfaces
      were characterized by the measurements of water contact angle, SEM and XPS. The
      anti-fouling properties of the modified surfaces were evaluated by reductions of
      fibrinogen absorption and cell (human dermal fibroblasts, hDFBs) adhesion.
      Results: SBMA hydrogel layers were coated on the PU substrates and these layers
      have a high affinity for water. The hydrogel coatings were highly stable for 7
      days, without a significant change in surface wettability. Importantly, the
      hydrogel-coated PU substrates decrease 80% of surface-adsorbed fibrinogen and
      surface-attached hDFBs (compared with uncoated PU substrates), indicating the
      excellent anti-fouling activities of modified surfaces. Conclusions: The hydrogel
      coated PU surfaces prepared by Fenton reaction with anti-fouling properties could
      have potential uses for implantable biomedical devices.

PMID- 29449962
TI  - Patient and public involvement in reducing health and care research waste.
AB  - Plain English summary: As much as 85 % of health research is believed to be
      wasted because it is not published or reported, the design is poor or does not
      consider what is already known in the topic area. Although a great deal of work
      has been done in the UK to reduce research waste, the role of patients and the
      public has not been discussed.This paper describes a survey, on the role of
      patients in reducing research waste, which was carried out as part of a larger
      piece of work on reducing waste in healthcare. The study found that patients were
      interested in reducing research waste. The key roles they play in research, for
      example being co-applicants for funding, members of project teams, co
      researchers, means they have some shared responsibility for making sure the
      quality of research is high. This includes finding out what is already known
      about a topic and getting the study design right before seeking funding,
      publishing and reporting the results when the study is finished. Recognising
      where waste happens is part of good management of a research study. Abstract:
      Background Eighty five per cent of health research expenditure is potentially
      wasted due to failure to publish research, unclear reporting of research that is
      published, and the failure of new research studies to systematically review
      previous research in the same topic area, poor study design and conduct. A great
      deal of progress has been made to address this issue but the role of patients and
      the public has not been considered.Main A small survey was undertaken, as part of
      a larger programme of work on reducing health and care waste, to understand the
      role of patients in reducing research waste. The study showed that patients are
      interested in this issue particularly in relation to the prioritisation of
      research and patient and public involvement.Conclusions Patients undertake key
      roles in the research process including co-applicancy, project management, or as
      co-researchers. This brings responsibility for ensuring high quality research and
      value for money. Responsibility for recognition of the potential for wasteful
      practices is part of the conduct and operation of research studies.

PMID- 29449960
TI  - Physician-initiated clinical study of limb ulcers treated with a functional
      peptide, SR-0379: from discovery to a randomized, double-blind, placebo
      controlled trial.
AB  - SR-0379 is a functional peptide that has wound healing effect with anti-microbial
      action, making it an ideal drug to prevent infection. To evaluate the safety,
      efficacy, and pharmacokinetics of SR-0379 for the treatment of leg ulcers, a
      physician-initiated, phase I/IIa, first-in-patient clinical study was designed. A
      multi-center, double-blind, randomized clinical study was conducted from October
      2015 to September 2016. The inclusion criteria for leg ulcers were (1) diabetes
      or critical limb ischemia and (2) wound size <6 cm in diameter. Twelve patients
      were randomized into four groups and administered 0.02%, 0.1%, or 0.5% SR-0379 or
      placebo treatment on skin ulcers once per day for 28 days. Efficiency was
      evaluated by determining the rate of wound size reduction as a primary endpoint
      at 4 weeks after the first treatment compared with the pre-treatment wound size.
      As a secondary endpoint, the DESIGN-R score index, time to wound closure, and the
      50% wound size reduction ratio were also evaluated. The safety of SR-0379 was
      evaluated during the study period. In the evaluation of efficiency, the skin
      ulcer reduction rates at the last evaluation were 44.73% for the 0.02% SR-0379
      group, 68.25% for the 0.1% group, and 71.61% for the 0.5% group, compared with
      9.95% for the placebo group. Six adverse events were reported in four patients,
      of which one occurred in the placebo group, and causal relationships to study
      drugs were denied for all six events. Treatment with SR-0379 for chronic leg
      ulcers was safe, well tolerated, and effective.

PMID- 29449961
TI  - Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and
      polarity.
AB  - Polarization of the airway epithelial cells (AECs) in the airway lumen is
      critical to the proper function of the mucociliary escalator and maintenance of
      lung health, but the cellular requirements for polarization of AECs are poorly
      understood. Using human AECs and cell lines, we demonstrate that cadherin-26
      (CDH26) is abundantly expressed in differentiated AECs, localizes to the cell
      apices near ciliary membranes, and has functional cadherin domains with homotypic
      binding. We find a unique and non-redundant role for CDH26, previously
      uncharacterized in AECs, in regulation of cell-cell contact and cell integrity
      through maintaining cytoskeletal structures. Overexpression of CDH26 in cells
      with a fibroblastoid phenotype increases contact inhibition and promotes
      monolayer formation and cortical actin structures. CDH26 expression is also
      important for localization of planar cell polarity proteins. Knockdown of CDH26
      in AECs results in loss of cortical actin and disruption of CRB3 and other
      proteins associated with apical polarity. Together, our findings uncover
      previously unrecognized functions for CDH26 in the maintenance of actin
      cytoskeleton and apicobasal polarity of AECs.

PMID- 29449964
TI  - Consequences of inadvertent intravitreal Mitomycin C injection.
AB  - Background: Mitomycin C (MMC) as an alkylating agent is miscellaneous an
      antineoplastic, antibiotic and ophthalmic agent. Here we aim to report a case of
      inadvertent intravitreal MMC injection instead of Avastin in case of diabetic
      macular edema. Case presentation: A 53 years old woman was planned to receive
      intravitreal Avastin injection, but accidentally, 0.05 ml of MMC 0.2% was
      injected. Best corrected visual acuity (BCVA) was 20/160 before injection. After
      2 days, patient was referred to a tertiary referral eye center. BCVA was hand
      motion at presentation. Intraocular pressure was 4 mmHg. In slit lamp exams,
      conjunctival injection, corneal edema, Descemet fold, anterior chamber and
      anterior vitreous cells were presented. Pars plana vitrectomy with peripheral
      vitreous shaving and silicone oil tamponade was performed. Electroretinography
      showed undetectable responses. Ultrasound biomicroscopy showed ciliary body
      shortening and detachment. Optical coherent tomography showed diffuse retinal
      edema the day after surgery, subretinal fluid pockets in 2 weeks, and atrophy
      with undetectable and intertwined layers 2 months later. Gradually, like the
      retina, iris became atrophic and pigments were dispersed diffusely over the lens
      and endothelium. Conclusion: MMC is showed to be severely toxic to intraocular
      tissues. In our case, iris and ciliary body became atrophic. Ciliary body
      detachment induced hypotony. Moreover, MMC induces retinal necrosis and atrophy.
      Visual outcome is profoundly poor.

PMID- 29449963
TI  - The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for
      accelerated etiologic diagnosis in critically ill infants.
AB  - Genetic disorders are a leading cause of morbidity and mortality in infants in
      neonatal and pediatric intensive care units (NICU/PICU). While genomic sequencing
      is useful for genetic disease diagnosis, results are usually reported too late to
      guide inpatient management. We performed an investigator-initiated, partially
      blinded, pragmatic, randomized, controlled trial to test the hypothesis that
      rapid whole-genome sequencing (rWGS) increased the proportion of NICU/PICU
      infants receiving a genetic diagnosis within 28 days. The participants were
      families with infants aged <4 months in a regional NICU and PICU, with illnesses
      of unknown etiology. The intervention was trio rWGS. Enrollment from October 2014
      to June 2016, and follow-up until November 2016. Of all, 26 female infants, 37
      male infants, and 2 infants of undetermined sex were randomized to receive rWGS
      plus standard genetic tests (n = 32, cases) or standard genetic tests alone (n =
      33, controls). The study was terminated early due to loss of equipoise: 73% (24)
      controls received genomic sequencing as standard tests, and 15% (five) controls
      underwent compassionate cross-over to receive rWGS. Nevertheless, intention to
      treat analysis showed the rate of genetic diagnosis within 28 days of enrollment
      (the primary end-point) to be higher in cases (31%, 10 of 32) than controls (3%,
      1 of 33; difference, 28% [95% CI, 10-46%]; p = 0.003). Among infants enrolled in
      the first 25 days of life, the rate of neonatal diagnosis was higher in cases
      (32%, 7 of 22) than controls (0%, 0 of 23; difference, 32% [95% CI, 11-53%];p =
      0.004). Median age at diagnosis (25 days [range 14-90] in cases vs. 130 days
      [range 37-451] in controls) and median time to diagnosis (13 days [range 1-84] in
      cases, vs. 107 days [range 21-429] in controls) were significantly less in cases
      than controls (p = 0.04). In conclusion, rWGS increased the proportion of
      NICU/PICU infants who received timely diagnoses of genetic diseases.

PMID- 29449965
TI  - Genetic diversity and cross-species transmission of kobuviruses in Vietnam.
AB  - Cross-species transmission of viruses poses a sustained threat to public health.
      Due to increased contact between humans and other animal species the possibility
      exists for cross-species transmissions and ensuing disease outbreaks. By using
      conventional PCR amplification and next generation sequencing, we obtained 130
      partial or full genome kobuvirus sequences from humans in a sentinel cohort in
      Vietnam and various mammalian hosts including bats, rodents, pigs, cats, and
      civets. The evolution of kobuviruses in different hosts was analysed using
      Bayesian phylogenetic methods. We estimated and compared time of origin of
      kobuviruses in different host orders; we also examined the cross-species
      transmission of kobuviruses within the same host order and between different host
      orders. Our data provide new knowledge of rodent and bat kobuviruses, which are
      most closely related to human kobuviruses. The novel bat kobuviruses isolated
      from bat roosts in Southern Vietnam were genetically distinct from previously
      described bat kobuviruses, but closely related to kobuviruses found in rodents.
      We additionally found evidence of frequent cross-species transmissions of
      kobuviruses within rodents. Overall, our phylogenetic analyses reveal multiple
      cross-species transmissions both within and among mammalian species, which
      increases our understanding of kobuviruses genetic diversity and the complexity
      of their evolutionary history.

PMID- 29449966
TI  - Raman spectroscopic imaging for quantification of depth-dependent and local
      heterogeneities in native and engineered cartilage.
AB  - Articular cartilage possesses a remarkable, mechanically-robust extracellular
      matrix (ECM) that is organized and distributed throughout the tissue to resist
      physiologic strains and provide low friction during articulation. The ability to
      characterize the make-up and distribution of the cartilage ECM is critical to
      both understand the process by which articular cartilage undergoes disease
      related degeneration and to develop novel tissue repair strategies to restore
      tissue functionality. However, the ability to quantitatively measure the spatial
      distribution of cartilage ECM constituents throughout the tissue has remained a
      major challenge. In this experimental investigation, we assessed the analytical
      ability of Raman micro-spectroscopic imaging to semi-quantitatively measure the
      distribution of the major ECM constituents in cartilage tissues. Raman
      spectroscopic images were acquired of two distinct cartilage tissue types that
      possess large spatial ECM gradients throughout their depth: native articular
      cartilage explants and large engineered cartilage tissue constructs. Spectral
      acquisitions were processed via multivariate curve resolution to decompose the
      "fingerprint" range spectra (800-1800 cm-1) to the component spectra of GAG,
      collagen, and water, giving rise to the depth dependent concentration profile of
      each constituent throughout the tissues. These Raman spectroscopic acquired
      profiles exhibited strong agreement with profiles independently acquired via
      direct biochemical assaying of spatial tissue sections. Further, we harness this
      spectroscopic technique to evaluate local heterogeneities through the depth of
      cartilage. This work represents a powerful analytical validation of the accuracy
      of Raman spectroscopic imaging measurements of the spatial distribution of
      biochemical components in a biological tissue and shows that it can be used as a
      valuable tool for quantitatively measuring the distribution and organization of
      ECM constituents in native and engineered cartilage tissue specimens.

PMID- 29449967
TI  - Retraining walking adaptability following incomplete spinal cord injury.
AB  - Introduction: Functional walking requires the ability to modify one's gait
      pattern to environmental demands and task goals-gait adaptability. Following
      incomplete spinal cord injury (ISCI), gait rehabilitation such as locomotor
      training (Basic-LT) emphasizes intense, repetitive stepping practice.
      Rehabilitation approaches focusing on practice of gait adaptability tasks have
      not been established for individuals with ISCIs but may promote recovery of
      higher level walking skills. The primary purpose of this case series was to
      describe and determine the feasibility of administering a gait adaptability
      retraining approach-Adapt-LT-by comparing the dose and intensity of Adapt-LT to
      Basic-LT. Case presentation: Three individuals with ISCIs (>1 year, AIS C or D)
      completed three weeks each (15 sessions) of Basic-LT and Adapt-LT. Interventions
      included practice on a treadmill with body weight support and practice overground
      (>=30 mins total). Adapt-LT focused on speed changes, obstacle negotiation, and
      backward walking. Training parameters (step counts, speeds, perceived exertion)
      were compared and outcomes assessed pre and post interventions. Based on
      completion of the protocol and similarities in training parameters in the two
      interventions, it was feasible to administer Adapt-LT with a similar dosage and
      intensity as Basic-LT. Additionally, the participants demonstrated gains in
      walking function and balance following each training type. Discussion:
      Rehabilitation that includes stepping practice with adaptability tasks is
      feasible for individuals with ISCIs. Further investigation is needed to determine
      the efficacy of Adapt-LT.

PMID- 29449968
TI  - Use of ambulatory blood pressure monitoring in adolescents with SCI: a case
      series.
AB  - Introduction: Due the impact of maturation on cardiovascular hemodynamics the
      degree of cardiovascular dysfunction, attributable to spinal cord injury (SCI),
      in the pediatric and adolescent population remains unclear. While few studies
      have begun to assess this, there is still a void in the literature regarding the
      prevalence of cardiovascular dysfunction and how best to identify and treat it in
      this population. Case presentation: The purpose of this case series is to present
      the cardiovascular profile of three adolescent patients with chronic SCI, ages 14
      16, following 2 or 3 days of 24-h Ambulatory Blood Pressure Monitoring (ABPM).
      Discussion: We found that there are variations across the different cases in most
      cardiovascular hemodynamic categories and a clarification of the International
      Standards to document remaining Autonomic Function after Spinal Cord Injury
      (ISAFSCI) may be needed to accurately identify the remaining autonomic
      cardiovascular function in the adolescent SCI population.

PMID- 29449969
TI  - Stigma and self-management: an Interpretative Phenomenological Analysis of the
      impact of chronic recurrent urinary tract infections after spinal cord injury.
AB  - Study Design: Qualitative, phenomenological design. Objectives: Neurogenic
      bladder dysfunction and urinary tract infection (UTI) are common secondary
      consequences to neurological damage to the spinal cord. This study sought to
      establish the impact of chronic, recurrent UTIs on people with spinal cord injury
      (SCI). Setting: Community sample, United Kingdom. Methods: Twelve participants
      with SCI, aged between 28 and 68 years, who had experienced at least three
      recurrent UTI events within the previous 12 months were recruited. Detailed
      qualitative information was obtained from semi-structured interviews, which
      lasted between 30 and 60 min. Interpretative Phenomenological Analysis was
      performed to explore the lived experience of UTIs. Results: Interview findings
      identified a range of factors related to the experience of recurrent UTIs in
      people with SCI. These were classified into the following themes: (1) Symptom
      Management Precedence, (2) Stigma-Motivated Risk Management and (3) Exhaustive
      Exploration of Treatment Options. Participants discussed management of acute
      exacerbations. Distress arose from perceptions of UTIs as potentially
      stigmatizing and fear of relying on antibiotics. Arising from this fear, many
      participants sought alternative prevention and management strategies.
      Conclusions: These results suggest that chronic recurrent UTIs act as major
      barriers to social participation, with adverse effects on quality of life of
      people with a neurogenic bladder after SCI. People with SCI would benefit from
      additional assessment of the impact of recurrent UTIs, so that healthcare
      professionals can address specific concerns, such as the psychosocial impact of
      urinary incontinence and stigmatizing views. Additional support to enhance self
      management and facilitate social participation should be provided.

PMID- 29449970
TI  - A systematic review: Children & Adolescents as simulated patients in health
      professional education.
AB  - Simulated patients (SP) contribute to health professional education for
      communication, clinical skills teaching, and assessment. Although a significant
      body of literature exists on the involvement of adult SPs, limited research has
      been conducted on the contribution of children and adolescents. This systematic
      review, using narrative summary with thematic synthesis, aims to report findings
      related to children/adolescents as simulated patients in health professions
      education (undergraduate or post-graduate). A systematic review of qualitative
      and quantitative literature published between 1980 and September 2014 was
      undertaken using databases including CINAHL, Ovid Medline and Scopus. The lack of
      literature related to the employment of children and adolescents in nursing
      education dictated the expansion of the search to the wider health professions.
      Key search terms related to the employment of children and adolescents in health
      professional education programs. A total of 58 studies reduced to 36 following
      exclusion based on abstract review. Twenty-two studies reached full text review;
      following application of inclusion and exclusion criteria, 15 English language
      studies involving children and/or adolescents in simulation formed part of this
      systematic review. Five key themes emerged: Process related to recruitment,
      duration and content of training programs, support and debriefing practice,
      ethical considerations, and effects of participation for key stakeholders such as
      children and adolescents, parent and faculty, and learner outcomes. The results
      suggest that the involvement of children and adolescents in simulation for
      education and assessment purposes is valuable and feasible. The review identified
      the potential for harm to children/adolescents; however, rigorous selection,
      training and support strategies can mitigate negative outcomes. The ability of
      children to portray a role consistently across assessments, and deliver
      constructive feedback remains ambiguous.

PMID- 29449971
TI  - Open access publishing in health and social care simulation research - Advances
      in Simulation.

PMID- 29449972
TI  - Complexity in simulation-based education: exploring the role of hindsight bias.
AB  - Simulation-based education (SBE) has the potential to misrepresent clinical
      practice as relatively simplistic, and as being made safer through simplistic
      behavioural explanations. This review provides an overview of a well-documented
      and robust psychological construct - hindsight bias in the context of learning in
      healthcare simulations. Motivating this review are our observations that post
      simulation debriefings may be oversimplified and biased by knowledge of scenario
      outcomes. Sometimes only limited consideration is given to issues that might be
      relevant to management in the complexity and uncertainty of real clinical
      practice. We use literature on hindsight bias to define the concept, inputs and
      implications. We offer examples from SBE where hindsight bias may occur and
      propose suggestions for mitigation. Influences of hindsight biases on SBE should
      be addressed by future studies.

PMID- 29449973
TI  - Observer roles that optimise learning in healthcare simulation education: a
      systematic review.
AB  - Background: Simulation is widely used in health professional education. The
      convention that learners are actively involved may limit access to this
      educational method. The aim of this paper is to review the evidence for learning
      methods that employ directed observation as an alternative to hands-on
      participation in scenario-based simulation training. We sought studies that
      included either direct comparison of the learning outcomes of observers with
      those of active participants or identified factors important for the engagement
      of observers in simulation. We systematically searched health and education
      databases and reviewed journals and bibliographies for studies investigating or
      referring to observer roles in simulation using mannequins, simulated patients or
      role play simulations. A quality framework was used to rate the studies. Methods:
      We sought studies that included either direct comparison of the learning outcomes
      of observers with those of active participants or identified factors important
      for the engagement of observers in simulation. We systematically searched health
      and education databases and reviewed journals and bibliographies for studies
      investigating or referring to observer roles in simulation using mannequins,
      simulated patients or role play simulations. A quality framework was used to rate
      the studies. Results: Nine studies met the inclusion criteria. Five studies
      suggest learning outcomes in observer roles are as good or better than hands-on
      roles in simulation. Four studies document learner satisfaction in observer
      roles. Five studies used a tool to guide observers. Eight studies involved
      observers in the debrief. Learning and satisfaction in observer roles is closely
      associated with observer tools, learner engagement, role clarity and contribution
      to the debrief. Learners that valued observer roles described them as affording
      an overarching view, examination of details from a distance, and meaningful
      feedback during the debrief. Learners who did not value observer roles described
      them as passive, or boring when compared to hands-on engagement in the simulation
      encounter. Conclusions: Learning outcomes and role satisfaction for observers is
      improved through learner engagement and the use of observer tools. The value that
      students attach to observer roles appear contingent on role clarity, use of
      observer tools, and inclusion of observers' perspectives in the debrief.

PMID- 29449974
TI  - A hybrid simulator model for the control of catastrophic external junctional
      haemorrhage in the military environment.
AB  - Catastrophic haemorrhage from extremity injuries has for a long time been the
      single most common cause of preventable death in the military environment. The
      effective use of extremity tourniquets has increased the survival of combat
      casualties, and exsanguination from isolated limb injuries is no longer the most
      common cause of death. Today, the most common cause of potentially preventable
      death is haemorrhage from the junctional zones, i.e. the most proximal part of
      the extremities, not amenable to standard tourniquets. Different training
      techniques to control catastrophic haemorrhage have been used by the Swedish
      Armed Forces in the pre-deployment training of physicians, nurses and medics for
      many years. The training techniques include different types of human patient
      simulators such as moulage patients and manikins. Preferred training conditions
      for the control of catastrophic haemorrhage include a high degree of realism, in
      combination with multiple training attempts. This report presents a new hybrid
      training model for catastrophic external junctional haemorrhage control. It
      offers a readily reproducible, simple and inexpensive opportunity to train
      personnel to deal with life threatening catastrophic junctional haemorrhage. In
      particular, this model offers an opportunity for non-medical military personnel
      in Sweden to practice control of realistic catastrophic haemorrhage, with
      multiple training attempts.

PMID- 29449976
TI  - Lessons for simulation-based education from social psychology.
AB  - Effective practice is informed by underlying theoretical models. Better awareness
      and understanding of such models can enhance reflection by practitioners on their
      current educational activities and so help drive the cycle of continuing
      improvement. In this article the author reflects on three ways in which a better
      understanding of social psychology gave insights into why some practices appeared
      to be more effective than others and some ways in which future practice could be
      altered. Social psychology places great emphasis on the importance of the
      situation in which people find themselves an how this impacts on their subsequent
      behaviour. The three areas specifically addressed in the article include factors
      which motivate and drive human activities, especially the importance of self
      esteem. Secondly, the relevance of the fundamental attribution error, which looks
      at our tendency as humans to ascribe personal attributes as the cause of the
      behaviour of others rather than the influence of external events. The third area
      to be explored is the role of acquiring scripts or heuristics that can broaden
      the range of activities than can be performed at a subconscious or intuitive
      level. For each concept, the author has included a brief illustration of its
      application to the practice of a simulation educator.

PMID- 29449975
TI  - Are simulated patients effective in facilitating development of clinical
      competence for healthcare students? A scoping review.
AB  - Background: The need to evaluate the effectiveness of SPs in improving clinical
      competence has attracted a heightened interest across the healthcare professions,
      with some prevailing gaps in their evidence. Using a scoping review approach,
      this study aims to provide an overview on the effectiveness of SPs in
      facilitating the development of clinical competence for healthcare students.
      Methods: This scoping review applied the first five out of the six-stage
      methodological framework developed by Levac et al. (Implementation Science 5:69),
      as follows: 1) Identify the research question; 2) identify relevant studies; 3)
      study selection; 4) charting the data; and 5) collating, summarising and
      reporting the results. The search was performed on four databases, including
      Medline, EMBASE, CINAHL and Scopus. Results: A total of 33 articles were included
      in this study (out of 968 identified), comprising of 20 cross-sectional studies,
      eight randomised controlled trials and five longitudinal studies. The studies
      were examined and categorised for further discussion in the three domains of
      clinical competence; technical, non-technical and cognitive skills. Overall, 24
      out of 33 studies showed effectiveness of SPs in facilitating students' clinical
      competence. Conclusion: This scoping review serves to provide guidance for future
      healthcare education development, by illustrating the effectiveness of SPs in
      improving students' clinical competence as evidenced in the literature. In doing
      so, it highlights the potential of SPs in facilitating students' acquisition of
      the necessary skills for clinical practice.

PMID- 29449977
TI  - The impact of contextualization on immersion in healthcare simulation.
AB  - Background: The aim of this paper is to explore how contextualization of a
      healthcare simulation scenarios impacts immersion, by using a novel objective
      instrument, the Immersion Score Rating Instrument. This instrument consists of 10
      triggers that indicate reduced or enhanced immersion among participants in a
      simulation scenario. Triggers refer to events such as jumps in time or space
      (sign of reduced immersion) and natural interaction with the manikin (sign of
      enhanced immersion) and can be used to calculate an immersion score. Methods: An
      experiment using a randomized controlled crossover design was conducted to
      compare immersion between two simulation training conditions for prehospital
      care: one basic and one contextualized. The Immersion Score Rating Instrument was
      used to compare the total immersion score for the whole scenario, the immersion
      score for individual mission phases, and to analyze differences in trigger
      occurrences. A paired t test was used to test for significance. Results: The
      comparison shows that the overall immersion score for the simulation was higher
      in the contextualized condition. The average immersion score was 2.17 (sd = 1.67)
      in the contextualized condition and -0.77 (sd = 2.01) in the basic condition (p <
      .001). The immersion score was significantly higher in the contextualized
      condition in five out of six mission phases. Events that might be disruptive for
      the simulation participants' immersion, such as interventions of the instructor
      and illogical jumps in time or space, are present to a higher degree in the basic
      scenario condition; while events that signal enhanced immersion, such as natural
      interaction with the manikin, are more frequently observed in the contextualized
      condition. Conclusions: The results suggest that contextualization of simulation
      training with respect to increased equipment and environmental fidelity as well
      as functional task alignment might affect immersion positively and thus
      contribute to an improved training experience.

PMID- 29449978
TI  - Using video-reflexive ethnography and simulation-based education to explore
      patient management and error recognition by pre-registration physiotherapists.
AB  - Background: Upon graduation, physiotherapists are required to manage clinical
      caseloads involving deteriorating patients with complex conditions. In
      particular, emergency on-call physiotherapists are required to provide
      respiratory/cardio-respiratory/cardiothoracic physiotherapy, out of normal
      working hours, without senior physiotherapist support. To optimise patient
      safety, physiotherapists are required to function within complex clinical
      environments, drawing on their knowledge and skills (technical and non
      technical), maintaining situational awareness and filtering unwanted stimuli from
      the environment. Prior to this study, the extent to which final-year
      physiotherapy students were able to manage an acutely deteriorating patient in a
      simulation context and recognise errors in their own practice was unknown.
      Methods: A focused video-reflexive ethnography study was undertaken to explore
      behaviours, error recognition abilities and personal experiences of 21 final-year
      (pre-registration) physiotherapy students from one higher education institution.
      Social constructivism and complexity theoretical perspectives informed the
      methodological design of the study. Video and thematic analysis of 12 simulation
      scenarios and video-reflexive interviews were undertaken. Results: Participants
      worked within the professional standards of physiotherapy practice expected of
      entry-level physiotherapists. Students reflected appropriate responses to their
      own and others' actions in the midst of uncertainty of the situation and
      physiological disturbances that unfolded during the scenario. However, they
      demonstrated a limited independent ability to recognise errors. Latent errors,
      active failures, error-producing factors and a series of effective defences to
      mitigate errors were identified through video analysis. Perceived influential
      factors affecting student performance within the scenario were attributed to
      aspects of academic and placement learning and the completion of a voluntary
      acute illness management course. The perceived value of the simulation scenario
      was enhanced by the opportunity to review their own simulation video with realism
      afforded by the scenario design. Conclusions: This study presents a unique
      insight into the experiences, skills, attitudes, behaviours and error recognition
      abilities of pre-registration physiotherapy students managing an acutely
      deteriorating patient in a simulation context. Findings of this research provide
      valuable insights to inform future research regarding physiotherapy practice,
      integration of educational methods to augment patient safety awareness and
      participant-led innovations in safe healthcare practice.

PMID- 29449979
TI  - OSCE best practice guidelines-applicability for nursing simulations.
AB  - Background: Objective structured clinical examinations (OSCEs) have been used for
      many years within healthcare programmes as a measure of students' and clinicians'
      clinical performance. OSCEs are a form of simulation and are often summative but
      may be formative. This educational approach requires robust design based on sound
      pedagogy to assure practice and assessment of holistic nursing care. As part of a
      project testing seven OSCE best practice guidelines (BPGs) across three sites,
      the BPGs were applied to an existing simulation activity. The aim of this study
      was to determine the applicability and value of the OSCE BPGs in an existing
      formative simulation. Methods: A mixed methods approach was used to address the
      research question: in what ways do OSCE BPGs align with simulations. The BPGs
      were aligned and compared with all aspects of an existing simulation activity
      offered to first-year nursing students at a large city-based university, prior to
      their first clinical placement in an Australian healthcare setting. Survey
      questions, comprised of Likert scales and free-text responses, used at other
      sites were slightly modified for reference to simulation. Students' opinions
      about the refined simulation activity were collected via electronic survey
      immediately following the simulation and from focus groups. Template analysis,
      using the BPGs as existing or a priori thematic codes, enabled interpretation and
      illumination of the data from both sources. Results: Few changes were made to the
      existing simulation plan and format. Students' responses from surveys (n = 367)
      and four focus groups indicated that all seven BPGs were applicable for
      simulations in guiding their learning, particularly in the affective domain, and
      assisting their perceived needs in preparing for upcoming clinical practice.
      Discussion: Similarities were found in the intent of simulation and OSCEs
      informed by the BPGs to enable feedback to students about holistic practice
      across affective, cognitive and psychomotor domains. The similarities in this
      study are consistent with findings from exploring the applicability of the BPGs
      for OSCEs in other nursing education settings, contexts, universities and
      jurisdictions. The BPGs also aligned with other frameworks and standards often
      used to develop and deliver simulations. Conclusions: Findings from this study
      provide further evidence of the applicability of the seven OSCE BPGs to inform
      the development and delivery of, in this context, simulation activities for
      nurses. The manner in which simulation is offered to large cohorts requires
      further consideration to meet students' needs in rehearsing the registered nurse
      role.

PMID- 29449980
TI  - Clinical exercise physiology students learning with older adults: an innovative
      simulation-based education programme.
AB  - In this paper, we report on a series of placements for clinical exercise
      physiology students in a simulation-based education environment with older,
      independent adults. The purpose of these placement opportunities was to help
      prepare students to work confidently and competently with older adults in primary
      healthcare settings. The effectiveness of these placements was measured through
      semi-structured interviews with the students, their supervisors and the volunteer
      patients, and also by analysing the content of the students' written reflection
      assignments. A combination of directed content analysis, informed by the research
      objectives and imposed upon the data, and conventional content analysis, in which
      codes were developed from themes emerging from the data, was adopted. Coding was
      based on units of meaning. Overall, the placement aims were met. Students
      reported increased confidence in communicating with older adults and in using the
      tools of their trade. This innovative simulation-based education experience
      helped students gain an understanding of their developing professional
      identities. However, the data show that some students still failed to recognise
      the value and importance of communication when working with older adults. The
      older adults reported that they enjoyed interacting with the students and
      believed that they had helped the students gain a positive impression of the
      cognitive and physical abilities of older adults. These older adults had also
      gained insight into the benefits of exercise physiology in terms of their own
      wellbeing. This paper demonstrates the benefits of engaging community support in
      developing healthcare workers and provides guidelines for replication of these
      innovative simulation-based education experiences. The paper is limited to
      reporting the social and community engagement benefits for older adults and the
      learning opportunities for the clinical exercise physiology students. Further
      research is needed to demonstrate the health gains for older adults who
      participate in such programmes.

PMID- 29449981
TI  - "Thinking on your feet"-a qualitative study of debriefing practice.
AB  - Background: Debriefing is a significant component of simulation-based education
      (SBE). Regardless of how and where immersive simulation is used to support
      learning, debriefing has a critical role to optimise learning outcomes. Although
      the literature describes different debriefing methods and approaches that
      constitute effective debriefing, there are discrepancies as to what is actually
      practised and how experts or experienced debriefers perceive and approach
      debriefing. This study sought to explore the self-reported practices of expert
      debriefers. Methods: We used a qualitative approach to explore experts'
      debriefing practices. Peer-nominated expert debriefers who use immersive manikin
      based simulations were identified in the healthcare simulation community across
      Australia. Twenty-four expert debriefers were purposively sampled to participate
      in semi-structured telephone interviews lasting 45-90 min. Interviews were
      transcribed and independently analysed using inductive thematic analysis.
      Results: Codes emerging through the data analysis clustered into four major
      categories: (1) Values: ideas and beliefs representing the fundamental principles
      that underpinned interviewees' debriefing practices. (2) Artistry: debriefing
      practices which are dynamic and creative. (3) Techniques: the specific methods
      used by interviewees to promote a productive and safe learning environment. (4)
      Development: changes in interviewees' debriefing practices over time.
      Conclusions: The "practice development triangle" inspired by the work of Handal
      and Lauvas offers a framework for our themes. A feature of the triangle is that
      the values of expert debriefers provide a foundation for associated artistry and
      techniques. This framework may provide a different emphasis for courses and
      programmes designed to support debriefing practices where microskill development
      is often privileged, especially those microskills associated with techniques
      (plan of action, creating a safe environment, managing learning objectives,
      promoting learner reflection and co-debriefing). Across the levels in the
      practice development triangle, the importance of continuing professional
      development is acknowledged. Strengths and limitations of the study are noted.

PMID- 29449982
TI  - Issues of cost-benefit and cost-effectiveness for simulation in health
      professions education.
AB  - Background: Simulation education can be costly-however, costs need to be
      considered against what you get in return to determine whether these costs are
      justified. Unfortunately in simulation education, evaluations that yield
      information about the return on investment are scarce. An economic evaluation
      provides a comparison of value. In short-what is it that is being obtained, what
      do you need to give up to get it, and how does that compare to what you get with
      the next best alternative? When educators are equipped with this knowledge, they
      will be better informed to know the place that simulation-based learning
      approaches should take in optimal course structures. Main body: This article
      provides an overview of the costs and consequences associated with simulation in
      healthcare education. It provides an outline of the benefits of using economic
      evaluations to inform decision-making by educators and clinicians concerning the
      most appropriate educational approaches. It also provides guidance for
      educational researchers interested in investigating the cost and value of their
      innovations. Conclusion: Measures of cost and value in simulation are required to
      provide information about the viability and sustainability of simulation
      education, enabling simulation education in health care to demonstrate its worth.

PMID- 29449983
TI  - Supporting transitions in medical career pathways: the role of simulation-based
      education.
AB  - Transitions, or periods of change, in medical career pathways can be challenging
      episodes, requiring the transitioning clinician to take on new roles and
      responsibilities, adapt to new cultural dynamics, change behaviour patterns, and
      successfully manage uncertainty. These intensive learning periods present risks
      to patient safety. Simulation-based education (SBE) is a pedagogic approach that
      allows clinicians to practise their technical and non-technical skills in a safe
      environment to increase preparedness for practice. In this commentary, we present
      the potential uses, strengths, and limitations of SBE for supporting transitions
      across medical career pathways, discussing educational utility, outcome and
      process evaluation, and cost and value, and introduce a new perspective on
      considering the gains from SBE. We provide case-study examples of the application
      of SBE to illustrate these points and stimulate discussion.

PMID- 29449984
TI  - Intensive simulation versus control in the assessment of time to skill competency
      and confidence of medical students to assess and manage cardiovascular and
      respiratory conditions-a pseudo-randomised trial.
AB  - Background: The Clinical Placement Enhancement Program (CPEP) is a simulation
      course for medical students learning the core topics of cardiovascular and
      respiratory medicine, incorporating patient safety and professionalism teaching
      and based on adult learning principles and proven educational theory. The aims of
      this study are to assess whether the CPEP delivered at the beginning of a
      clinical rotation would result in competency outcomes that are at least
      equivalent to those achieved through a standard 6-week programme and whether this
      programme would increase student confidence levels in assessing and managing
      patients with cardiovascular and respiratory conditions. Methods: This was a
      pseudo-randomised control trial between two groups of medical students from one
      clinical school. The intervention group participated in CPEP, a 4-day immersive
      simulation course, in the first week of their cardiac and respiratory medicine
      clinical rotation. The control group participants attended the normal programme
      of the 6-week cardiovascular and respiratory medicine clinical rotation. The
      programme and student competence was assessed using Observed Structured Clinical
      Examinations (OSCEs) and self-reported confidence surveys. Results: There was no
      significant difference in OSCE scoring between the intervention group (examined
      in week one of their clinical rotation following CPEP) and the control group
      (examined at the end of their full clinical rotation). Students exposed to CPEP
      started their clinical rotation with confidence levels similar to those reported
      by the control group at the end of their rotation. Confidence levels of CPEP
      students were higher at the end of the rotation compared to those of the control
      group. Conclusions: Based on OSCE results, immersion into a 4-day simulation
      based teaching programme at the start of a clinical rotation resulted in skill
      competency levels that were equivalent to those obtained after a full clinical
      rotation of 6 weeks. CPEP improved students' confidence levels in the assessment
      and management of patients presenting with cardiovascular and respiratory
      conditions. Simulation utilised in courses such as CPEP has the potential to
      enhance the overall learning experience in medical school clinical rotations.

PMID- 29449985
TI  - Learning curve patterns generated by a training method for laparoscopic small
      bowel anastomosis.
AB  - Background: The identification of developmental curve patterns generated by a
      simulation-based educational method and the variables that can accelerate the
      learning process will result in cost-effective training. This study describes the
      learning curves of a simulation-based instructional design (ID) that uses ex vivo
      animal models to teach laparoscopic latero-lateral small bowel anastomosis.
      Methods: Twenty general surgery residents were evaluated on their performance of
      laparoscopic latero-lateral jejuno-jejunal anastomoses (JJA) and gastro-jejunal
      anastomoses (GJA), using swine small bowel and stomach on an endotrainer. The ID
      included the following steps: (1) provision of references and videos
      demonstrating the surgical technique, (2) creation of an engaging context for
      learning, (3) critical review of the literature and video on the procedures, (4)
      demonstration of the critical steps, (5) hands-on practice, (6) in-action
      instructor's feedback, (7) quality assessment, (8) debriefing at the end of the
      session, and (9) deliberate and repetitive practice. Time was recorded from the
      beginning to the completion of the procedure, along with the presence or absence
      of anastomotic leaks. Results: The participants needed to perform 23.8 +/- 6.96
      GJA (12-35) and 24.2 +/- 6.96 JJA (9-43) to attain proficiency. The starting
      point of the learning curve was higher for the GJA than for the JJA, although the
      slope and plateau were parallel. Further, four types of learning curves were
      identified: (1) exponential, (2) rapid, (3) slow, and (4) no tendency. The type
      of pattern could be predicted after procedure number 8. Conclusions: These
      findings may help to identify the learning curve of a trainee early in the
      developmental process, estimate the number of sessions required to reach a
      performance goal, determine a trainee's readiness to practice the procedure on
      patients, and identify the subjects who lack the innate technical abilities. It
      may help motivated individuals to become reflective and self-regulated learners.
      Moreover, the standardization of the ID may help to measure the effectiveness of
      learning strategies and make comparisons with other educational strategies.

PMID- 29449986
TI  - Measuring participants' immersion in healthcare simulation: the development of an
      instrument.
AB  - Background: Immersion is important for simulation-based education; however,
      questionnaire-based instruments to measure immersion have some limitations. The
      aim of the present work is to develop a new instrument to measure immersion among
      participants in healthcare simulation scenarios. Methods: The instrument was
      developed in four phases: trigger identification, content validity scores, inter
      rater reliability analysis and comparison with an existing immersion measure
      instrument. A modified Delphi process was used to develop the instrument and to
      establish validity and reliability. The expert panel consisted of 10 researchers.
      All the researchers in the team had previous experience of simulation in the
      health and/or fire and rescue services as researchers and/or educators and
      simulation designers. To identify triggers, the panel members independently
      screened video recordings from simulation scenarios. Here, a trigger is an event
      in a simulation that is considered a sign of reduced or enhanced immersion among
      simulation participants. Results: The result consists of the Immersion Score
      Rating Instrument (ISRI). It contains 10 triggers, of which seven indicate
      reduced and three enhanced immersion. When using ISRI, a rater identifies trigger
      occurrences and assigns them strength between 1 and 3. The content validity
      analysis shows that all the 10 triggers meet an acceptable content validity index
      for items (I-CVI) standard. The inter-rater reliability (IRR) among raters was
      assessed using a two-way mixed, consistency, average-measures intra-class
      correlation (ICC). The ICC for the difference between weighted positive and
      negative triggers was 0.92, which indicates that the raters are in agreement.
      Comparison with results from an immersion questionnaire mirrors the ISRI results.
      Conclusions: In conclusion, we present a novel and non-intrusive instrument for
      identifying and rating the level of immersion among participants in healthcare
      simulation scenarios.

PMID- 29449987
TI  - The reliability and usability of the Anesthesiologists' Non-Technical Skills
      (ANTS) system in simulation research.
AB  - Background: Non-technical skills (NTS) such as leadership and team work are
      important in providing good quality of care. One system to assess physicians' NTS
      is the Anesthesiologists' Non-Technical Skills (ANTS) system. The present study
      evaluates the ANTS system on the interrater reliability and usability for
      research purposes. Methods: Ten anesthesiologists and 20 anesthesiology residents
      performed two resuscitation scenarios (with and without the presence of
      distractors) in a simulation room with a full-scale patient simulator. The
      scenarios were videotaped. Two independent raters rated the NTS of the
      anesthesiologists using the ANTS system. The intraclass correlation coefficients
      (ICC) were calculated to determine the interrater reliability of both the total
      NTS score and the measured differences between the two scenarios. The raters
      filled out a questionnaire to obtain insights in the usability of the ANTS system
      for research purposes. Results: The ICC for the total score of the NTS was
      substantial (0.683), and the ICC of the elements varied between 0.371 for
      assessing capabilities and 0.670 for providing and maintaining standards. The
      intraclass correlation coefficient of measuring differences was fair (0.502). The
      raters judged the usability as good. Conclusions: The ANTS system was reliable
      for the total score and usable to measure physicians' NTS in a research setting.
      However, there was variation between the reliability of the elements. We
      recommend that if the ANTS is used for research, a pilot study should determine
      elements not applicable or observable in the scenario of interest; these elements
      should be excluded from the study.

PMID- 29449988
TI  - Engaging patients and clinicians through simulation: rebalancing the dynamics of
      care.
AB  - This paper proposes simulation-based enactment of care as an innovative and
      fruitful means of engaging patients and clinicians to create collaborative
      solutions to healthcare issues. This use of simulation is a radical departure
      from traditional transmission models of education and training. Instead, we frame
      simulation as co-development, through which professionals, patients and publics
      share their equally (though differently) expert perspectives. The paper argues
      that a process of participatory design can bring about new insights and that
      simulation offers understandings that cannot easily be expressed in words.
      Drawing on more than a decade of our group's research on simulation and
      engagement, the paper summarises findings from studies relating to clinician
      patient collaboration and proposes a novel approach to address the current need.
      The paper outlines a mechanism whereby pathways of care are jointly created,
      shaped, tested and refined by professionals, patients, carers and others who are
      affected and concerned by clinical care.

PMID- 29449989
TI  - The effect of implementing cognitive load theory-based design principles in
      virtual reality simulation training of surgical skills: a randomized controlled
      trial.
AB  - Background: Cognitive overload can inhibit learning, and cognitive load theory
      based instructional design principles can be used to optimize learning
      situations. This study aims to investigate the effect of implementing cognitive
      load theory-based design principles in virtual reality simulation training of
      mastoidectomy. Methods: Eighteen novice medical students received 1 h of self
      directed virtual reality simulation training of the mastoidectomy procedure
      randomized for standard instructions (control) or cognitive load theory-based
      instructions with a worked example followed by a problem completion exercise
      (intervention). Participants then completed two post-training virtual procedures
      for assessment and comparison. Cognitive load during the post-training procedures
      was estimated by reaction time testing on an integrated secondary task. Final
      product analysis by two blinded expert raters was used to assess the virtual
      mastoidectomy performances. Results: Participants in the intervention group had a
      significantly increased cognitive load during the post-training procedures
      compared with the control group (52 vs. 41 %, p = 0.02). This was also reflected
      in the final-product performance: the intervention group had a significantly
      lower final-product score than the control group (13.0 vs. 15.4, p < 0.005).
      Conclusions: Initial instruction using worked examples followed by a problem
      completion exercise did not reduce the cognitive load or improve the performance
      of the following procedures in novices. Increased cognitive load when part tasks
      needed to be integrated in the post-training procedures could be a possible
      explanation for this. Other instructional designs and methods are needed to lower
      the cognitive load and improve the performance in virtual reality surgical
      simulation training of novices.

PMID- 29449990
TI  - Impact of simulation-based training in surgical chest tube insertion on a model
      of traumatic pneumothorax.
AB  - Background: Chest tube insertion is required for most cases of traumatic
      pneumothorax. However, this procedure entails risks of potentially life
      threatening complications. A "surgical" approach is widely recommended to
      minimize these risks. Simulation-based education has previously been used in
      surgical chest tube insertion, but not been subjected to rigorous evaluation.
      Methods: The primary objective was to evaluate the success rate of surgical chest
      tube insertion in a task trainer (previously published). Secondary objectives
      were to assess performance with a performance assessment scale (previously
      designed), to measure the time of insertion, and to seek out a correlation
      between the learner's status, experience, and performance and success rate.
      Participants were surveyed for realism of the model and satisfaction; 65
      participants (18 residents, 47 senior physicians) were randomized into SIM+ or
      SIM- groups. Both groups received didactic lessons. The SIM+ group was assigned
      deliberate practice on the model under supervision. Both groups were assessed on
      the model 1 month later. Results: There was no difference between the SIM+ (n =
      34) and SIM- (n = 31) groups regarding status (p = 0.44) or previous surgical
      insertion (p = 0.12). Success rate was 97 % (SIM+) and 58 % (SIM-), p = 0.0002.
      Performance score was 16.29 +/- 1.82 (SIM+) and 11.39 +/- 3.67 (SIM-), p = 3.13 *
      10-8. SIM+ presented shorter dissection time than SIM- (p = 0.047), but procedure
      time was similar (p = 0.71). Status or experience was not correlated with success
      rate, performance score, procedure time, or dissection time. SIM+ gained more
      self-confidence, judged the model more realistic, and were more satisfied than
      SIM-. Conclusions: Simulation-based education significantly improved the success
      rate and performance of surgical chest tube insertion on a traumatic pneumothorax
      model.

PMID- 29449991
TI  - From simulation research to education policy: how much evidence is enough?

PMID- 29449992
TI  - Non-Technical Skills Bingo-a game to facilitate the learning of complex concepts.
AB  - Acquiring the concepts of non-technical skills (NTS) beyond a superficial level
      is a challenge for healthcare professionals and simulation faculty. Current
      simulation-based approaches to teach NTS are challenged when learners have to
      master NTS concepts, clinically challenging situations, and simulation as a
      complex technique. The combination of all three aspects might overwhelm learners.
      To facilitate the deeper comprehension of NTS concepts, we describe an innovative
      video-based game, the Non-Technical Skills (NTS) Bingo. Participants get NTS
      Bingo cards that show five NTS elements each. While observing (non-medical) video
      clips, they try to find examples for the elements on their cards, typically
      observable behaviours that match a given element. After the video, participants
      "defend" their solution in a discussion with the game leader and other players.
      This discussion and the reflection aim to deepen the processing of the NTS
      concepts. We provide practical guidance for the conduct of NTS Bingo, including a
      selection of usable video clips and tips for the facilitated discussion after a
      clip. We use NTS in anaesthesia as example and provide guidance on how to adapt
      NTS Bingo to other disciplines. NTS Bingo is based on theoretical considerations
      on concept learning, which we describe to support the rationale for its conduct.

PMID- 29449993
TI  - A joint leap into a future of high-quality simulation research-standardizing the
      reporting of simulation science.

PMID- 29449994
TI  - Reporting guidelines for health care simulation research: extensions to the
      CONSORT and STROBE statements.
AB  - Background: Simulation-based research (SBR) is rapidly expanding but the quality
      of reporting needs improvement. For a reader to critically assess a study, the
      elements of the study need to be clearly reported. Our objective was to develop
      reporting guidelines for SBR by creating extensions to the Consolidated Standards
      of Reporting Trials (CONSORT) and Strengthening the Reporting of Observational
      Studies in Epidemiology (STROBE) Statements. Methods: An iterative multistep
      consensus-building process was used on the basis of the recommended steps for
      developing reporting guidelines. The consensus process involved the following:
      (1) developing a steering committee, (2) defining the scope of the reporting
      guidelines, (3) identifying a consensus panel, (4) generating a list of items for
      discussion via online premeeting survey, (5) conducting a consensus meeting, and
      (6) drafting reporting guidelines with an explanation and elaboration document.
      Results: The following 11 extensions were recommended for CONSORT: item 1
      (title/abstract), item 2 (background), item 5 (interventions), item 6 (outcomes),
      item 11 (blinding), item 12 (statistical methods), item 15 (baseline data), item
      17 (outcomes/ estimation), item 20 (limitations), item 21 (generalizability), and
      item 25 (funding). The following 10 extensions were recommended for STROBE: item
      1 (title/abstract), item 2 (background/rationale), item 7 (variables), item 8
      (data sources/measurement), item 12 (statistical methods), item 14 (descriptive
      data), item 16 (main results), item 19 (limitations), item 21 (generalizability),
      and item 22 (funding). An elaboration document was created to provide examples
      and explanation for each extension. Conclusions: We have developed extensions for
      the CONSORT and STROBE Statements that can help improve the quality of reporting
      for SBR (Sim Healthcare 00:00-00, 2016).

PMID- 29449995
TI  - Ethical reasoning through simulation: a phenomenological analysis of student
      experience.
AB  - Background: Medical students transitioning into professional practice feel
      underprepared to deal with the emotional complexities of real-life ethical
      situations. Simulation-based learning (SBL) may provide a safe environment for
      students to probe the boundaries of ethical encounters. Published studies of
      ethics simulation have not generated sufficiently deep accounts of student
      experience to inform pedagogy. The aim of this study was to understand students'
      lived experiences as they engaged with the emotional challenges of managing
      clinical ethical dilemmas within a SBL environment. Methods: This qualitative
      study was underpinned by an interpretivist epistemology. Eight senior medical
      students participated in an interprofessional ward-based SBL activity
      incorporating a series of ethically challenging encounters. Each student wore
      digital video glasses to capture point-of-view (PoV) film footage. Students were
      interviewed immediately after the simulation and the PoV footage played back to
      them. Interviews were transcribed verbatim. An interpretative phenomenological
      approach, using an established template analysis approach, was used to
      iteratively analyse the data. Results: Four main themes emerged from the
      analysis: (1) 'Authentic on all levels?', (2)'Letting the emotions flow', (3)
      'Ethical alarm bells' and (4) 'Voices of children and ghosts'. Students
      recognised many explicit ethical dilemmas during the SBL activity but had
      difficulty navigating more subtle ethical and professional boundaries. In
      emotionally complex situations, instances of moral compromise were observed (such
      as telling an untruth). Some participants felt unable to raise concerns or
      challenge unethical behaviour within the scenarios due to prior negative
      undergraduate experiences. Conclusions: This study provided deep insights into
      medical students' immersive and embodied experiences of ethical reasoning during
      an authentic SBL activity. By layering on the human dimensions of ethical
      decision-making, students can understand their personal responses to emotion,
      complexity and interprofessional working. This could assist them in framing and
      observing appropriate ethical and professional boundaries and help smooth the
      transition into clinical practice.

PMID- 29449997
TI  - A conceptual framework of game-informed principles for health professions
      education.
AB  - Games have been used for training purposes for many years, but their use remains
      somewhat underdeveloped and under-theorized in health professional education.
      This paper considers the basis for using serious games (games that have an
      explicit educational purpose) in health professional education in terms of their
      underlying concepts and design principles. These principles can be understood as
      a series of game facets: competition and conflict, chance and luck, experience
      and performance, simulation and make-believe, tactics and strategies, media,
      symbols and actions, and complexity and difficulty. Games are distinct and bound
      in ways that other health professional education activities are not. The
      differences between games and simulation can be understood in terms of the
      interconnected concepts of isomorphism (convergence with real-world practice) and
      anisomorphism (divergence from real-world practice). Gaming facets can extend the
      instructional design repertoire in health professional education.

PMID- 29449996
TI  - Simulation reframed.
AB  - Background: Simulation is firmly established as a mainstay of clinical education,
      and extensive research has demonstrated its value. Current practice uses
      inanimate simulators (with a range of complexity, sophistication and cost) to
      address the patient 'as body' and trained actors or lay people (Simulated
      Patients) to address the patient 'as person'. These approaches are often
      separate.Healthcare simulation to date has been largely for the training and
      assessment of clinical 'insiders', simulating current practices. A close coupling
      with the clinical world restricts access to the facilities and practices of
      simulation, often excluding patients, families and publics. Yet such perspectives
      are an essential component of clinical practice. Main body: This paper argues
      that simulation offers opportunities to move outside a clinical 'insider' frame
      and create connections with other individuals and groups. Simulation becomes a
      bridge between experts whose worlds do not usually intersect, inviting an
      exchange of insights around embodied practices-the 'doing' of medicine-without
      jeopardising the safety of actual patients.Healthcare practice and education take
      place within a clinical frame that often conceals parallels with other domains of
      expert practice. Valuable insights emerge by viewing clinical practice not only
      as the application of medical science but also as performance and
      craftsmanship.Such connections require a redefinition of simulation. Its essence
      is not expensive elaborate facilities. Developments such as hybrid, distributed
      and sequential simulation offer examples of how simulation can combine 'patient
      as body' with 'patient as person' at relatively low cost, democratising
      simulation and exerting traction beyond the clinical sphere.The essence of
      simulation is a purposeful design, based on an active process of selection from
      an originary world, abstraction of what is criterial and re-presentation in
      another setting for a particular purpose or audience. This may be done within
      traditional simulation centres, or outside in local communities, public spaces or
      arts and performance venues. Conclusions: Simulation has established a central
      role in clinical education but usually focuses on learning to do things as they
      are already done. Imaginatively designed, simulation offers untapped potential
      for deep engagement with patients, publics and experts outside medicine.

PMID- 29449998
TI  - How to debrief teamwork interactions: using circular questions to explore and
      change team interaction patterns.
AB  - We submit that interaction patterns within healthcare teams should be more
      comprehensively explored during debriefings in simulation-based training because
      of their importance for clinical performance. We describe how circular questions
      can be used for that purpose. Circular questions are based on social
      constructivism. They include a variety of systemic interviewing methods. The
      goals of circular questions are to explore the mutual dependency of team members'
      behavior and recurrent behavior patterns, to generate information, to foster
      perspective taking, to "fluidize" problems, and to put actions into relational
      contexts. We describe the nature of circular questions, the benefits they offer,
      and ways of applying them during debriefings.

PMID- 29449999
TI  - "Hand-it-on": an innovative simulation on the relation of non-technical skills to
      healthcare.
AB  - Non-technical skills (NTS) are an integral part of the abilities healthcare
      professionals need to optimally care for patients. Integrating NTS into the
      already complex tasks of healthcare can be a challenge for clinicians.
      Integrating NTS into simulation-based training increases the demands for
      simulation instructors with regard to scenario design, conduct, and debriefing.
      We introduce a simulation game, Hand-it-on, that can trigger discussions on how
      NTS can influence work processes. Hand-it-on aims to help clinicians and
      simulation instructors alike to improve their understanding of NTS concepts and
      where they can apply them in their work. It complements existing approaches to
      teaching NTS by limiting the complexity of the game and by removing medical
      content, allowing learners to concentrate on NTS. Hand-it-on is relevant for
      groups and teams working across the range of different healthcare contexts.
      During Hand-it-on, participants stand in a circle and hand on everyday objects to
      each other according to simple rules, resulting in many events that can be
      debriefed in relation to safe patient care. We describe both the conduct of Hand
      it-on and ideas on how to debrief participants. We provide variations that can be
      used in different contexts, focusing the exercise on different learning goals. We
      also offer the theoretical rationale for using an out-of-context simulation in
      combination with other forms of teaching. Although we did not evaluate Hand-it-on
      formally, oral feedback from participants and the replication of Hand-it-on by
      many simulation teams support its value.

PMID- 29450000
TI  - Validation of educational assessments: a primer for simulation and beyond.
AB  - Background: Simulation plays a vital role in health professions assessment. This
      review provides a primer on assessment validation for educators and education
      researchers. We focus on simulation-based assessment of health professionals, but
      the principles apply broadly to other assessment approaches and topics. Key
      principles: Validation refers to the process of collecting validity evidence to
      evaluate the appropriateness of the interpretations, uses, and decisions based on
      assessment results. Contemporary frameworks view validity as a hypothesis, and
      validity evidence is collected to support or refute the validity hypothesis
      (i.e., that the proposed interpretations and decisions are defensible). In
      validation, the educator or researcher defines the proposed interpretations and
      decisions, identifies and prioritizes the most questionable assumptions in making
      these interpretations and decisions (the "interpretation-use argument"),
      empirically tests those assumptions using existing or newly-collected evidence,
      and then summarizes the evidence as a coherent "validity argument." A framework
      proposed by Messick identifies potential evidence sources: content, response
      process, internal structure, relationships with other variables, and
      consequences. Another framework proposed by Kane identifies key inferences in
      generating useful interpretations: scoring, generalization, extrapolation, and
      implications/decision. We propose an eight-step approach to validation that
      applies to either framework: Define the construct and proposed interpretation,
      make explicit the intended decision(s), define the interpretation-use argument
      and prioritize needed validity evidence, identify candidate instruments and/or
      create/adapt a new instrument, appraise existing evidence and collect new
      evidence as needed, keep track of practical issues, formulate the validity
      argument, and make a judgment: does the evidence support the intended use?
      Conclusions: Rigorous validation first prioritizes and then empirically evaluates
      key assumptions in the interpretation and use of assessment scores. Validation
      science would be improved by more explicit articulation and prioritization of the
      interpretation-use argument, greater use of formal validation frameworks, and
      more evidence informing the consequences and implications of assessment.

PMID- 29450001
TI  - Simulation as a toolkit-understanding the perils of blood transfusion in a
      complex health care environment.
AB  - Background: Administration of blood is a complex process requiring vigilance and
      effective teamwork. Despite strict policies and training on blood administration,
      errors still occur and can lead to mistransfusion with adverse patient outcomes.
      We used an in situ simulated scenario within an operating room (OR) to identify
      weaknesses in the current process and hazards that could contribute to
      mistransfusion. Methods: A process checklist of critical steps of safe
      transfusion was developed based on a large academic centre's internal hospital
      policy and practice. Ten standardized operating room scenarios were conducted
      involving management of postoperative bleeding. Scenarios lasted 20 min or until
      blood transfusion was started. Debriefing followed immediately. Video recordings
      were reviewed, scored, and evaluated for team performance. Latent safety threats
      were identified. Focus groups further helped to identify rationale for decisions
      made. Participants completed questionnaires to evaluate the exercise. Results:
      Forty-three experienced OR professionals participated. Of the 19 steps identified
      as essential for the safe administration of blood components, the median number
      of steps correctly completed per team was 11. The largest number of errors
      occurred when different team members interacted and during the immediate pre
      transfusion check. We report that this type of learning immediately increased
      participants' self-reported ability to perform in a team (90%) and to improve
      clinical care (88%). Conclusions: In situ simulation is valuable in identifying
      common susceptibilities in blood administration error in a complex healthcare
      organization. Administrators and clinicians may wish to use simulation as an
      opportunity for system improvement in the delivery of quality care.

PMID- 29450002
TI  - Sharing simulation-based training courses between institutions: opportunities and
      challenges.
AB  - Background: Sharing simulation-based training (SBT) courses between institutions
      could reduce time to develop new content but also presents challenges. We
      evaluate the process of sharing SBT courses across institutions in a mixed method
      study estimating the time required and identifying barriers and potential
      solutions. Methods: Two US academic medical institutions explored instructor
      experiences with the process of sharing four courses (two at each site) using
      personal interviews and a written survey and estimated the time needed to develop
      new content vs implement existing SBT courses. Results: The project team spent
      approximately 618 h creating a collaboration infrastructure to support course
      sharing. Sharing two SBT courses was estimated to save 391 h compared with
      developing two new courses. In the qualitative analysis, participants noted the
      primary benefit of course sharing was time savings. Barriers included difficulty
      finding information and understanding overall course flow. Suggestions for
      improvement included establishing a standardized template, clearly identifying
      the target audience, providing a course overview, communicating with someone
      familiar with the original SBT course, employing an intuitive file-sharing
      platform, and considering local culture, context, and needs. Conclusions: Sharing
      SBT courses between institutions is feasible but not without challenges. An
      initial investment in a sharing infrastructure may facilitate downstream time
      savings compared with developing content de novo.

PMID- 29450003
TI  - Simulation and mental health outcomes: a scoping review.
AB  - Background: A scoping review was conducted in order to map and determine the gaps
      in literature on the impact of simulation as an educational approach to improve
      mental health care outcomes. As it became apparent that no literature existed on
      this topic, the study aimed to examine the educational impact of simulation on
      mental health education. Methods: An established five-stage scoping methodology
      was used: (1) identification of the research question, (2) identification of
      relevant studies, (3) study selection, (4) charting the data and (5) collation,
      summarising and reporting of results. CINAHL, ProQuest, PubMed, MEDLINE, EMBASE
      and PsychINFO databases were searched. These databases were deemed to represent a
      majority of the literature while accommodating for the particular search strategy
      used for this review. Websites that provide grey literature were also searched
      for articles of relevance. Results: A total of 48 articles were included in this
      review, with a considerable portion of studies conducted in the USA and UK.
      Others were conducted in an array of locations including Australia, Canada, Iran
      and Taiwan. Of the included articles, seven groups of simulation methods
      (including standardised patients, virtual reality and manikins as patients) were
      evident, with standardised patients being most prominent. Conclusions: Literature
      is lacking to evidence the benefit of simulation on mental health patient
      outcomes. However, the available literature suggests a variety of simulation
      based education, and training methods are currently being used within mental
      healthcare education. The findings do suggest some methods of simulation, such as
      the use of standardised patients, are more commonly used in education and have
      been deemed as effective to assist in mental health education. As no article
      specifically examining the mental health outcomes of patients treated by health
      professionals taught by simulation was identified, the educational outcomes
      outlined in this paper may be used to inform further research, incorporating
      mental health patient outcomes.

PMID- 29450004
TI  - Serious games for health: three steps forwards.
AB  - Serious games are educational tools which are more and more used in patient and
      health professional education. In this article, we discuss three main points that
      developers and educators need to address during the development of a serious game
      for health. We first explain how to develop motivating serious games by finding a
      point where the intrinsic and extrinsic motivations of end users can converge.
      Then, we propose to identify the features of serious games which enhance their
      learning effectiveness on the basis of a framework derived from cognitive science
      and called "the four pillars of learning." Finally, we discuss issues and
      solutions related to the evaluation of serious games.

PMID- 29450005
TI  - Designing in situ simulation in the emergency department: evaluating safety
      attitudes amongst physicians and nurses.
AB  - Background: This intervention study aimed to enhance patient safety attitudes
      through the design of an in situ simulation program based on a needs analysis
      involving thematic analysis of patient safety data and short-term ethnography.
      The study took place at an Emergency Department (ED) in the Central Region of
      Denmark. Research suggests that poor handover communication can increase the
      likelihood of critical incidents and adverse events in the ED. Furthermore,
      simulation is an effective strategy for training handover communication skills.
      Research is lacking, however, on how to use patient safety data and a needs
      analysis to the design of in situ simulation communication training. Methods:
      This is a prospective pre-post study investigating the interventional effects of
      in situ simulation. It used a three-pronged strategy: (1) thematic analysis of
      patient safety data consisting of reported critical incidents and adverse events,
      (2) a needs analysis based on short-term ethnography in the ED, and (3) pre-post
      evaluation using the validated Safety Attitudes Questionnaire (SAQ) and the
      Trainee Reactions Score. Results: Sixteen different healthcare teams participated
      composed by 9 physicians and 30 nurses. In the SAQ, participating staff scored
      their safety attitudes in six categories (n = 39). Two measures where
      significantly higher for the post-SAQ than those for the pre-SAQ: teamwork
      climate (p < 0.001) and safety climate (p < 0.05). The Trainee Reactions Score
      showed that the training was positively evaluated. Conclusions: This study
      designed a feasible strategy for implementing in situ simulation based on a needs
      analysis of critical incidents and adverse events and short-term ethnography.

PMID- 29450006
TI  - An experimental study on the impact of clinical interruptions on simulated
      trainee performances of central venous catheterization.
AB  - Background: Interruptions are common in the healthcare setting. This experimental
      study compares the effects of interruptions on simulated performances of central
      venous catheterization during a highly versus minimally complex portion of the
      task. Methods: Twenty-six residents were assigned to interruptions during tasks
      that are (1) highly complex: establishing ultrasound-guided venous access
      (experimental group, n = 15) or (2) minimally complex: skin cleansing (control
      group, n = 11). Primary outcomes were (a) performance scores at three time points
      measured with a validated checklist, (b) time spent on the respective tasks, and
      (c) number of attempts to establish venous access. Results: Repeated measure
      analyses of variances of performance scores over time indicated no main effect of
      time or group. The interaction between time and group was significant: F (2, 44)
      = 4.28, p = 0.02, and partial eta2 = 0.16, indicating a large effect size. The
      experimental group scores decreased steadily over time, while the control group
      scores increased with time. The experimental group required longer to access the
      vein (148 s; interquartile range (IQR) 60 to 361 vs. 44 s; IQR 27 to 133 s; p =
      0.034). Median number of attempts to establish venous access was higher in the
      experimental group (2, IQR 1-7 vs. 1, IQR 1-2; p = 0.03). Conclusions:
      Interruptions during a highly complex task resulted in a consistent decrement in
      performance scores, longer time required to perform the task, and a higher number
      of venous access attempts than interruptions during a minimally complex tasks. We
      recommend avoiding interrupting trainees performing bedside procedures.

PMID- 29450007
TI  - Conducting multicenter research in healthcare simulation: Lessons learned from
      the INSPIRE network.
AB  - Simulation-based research has grown substantially over the past two decades;
      however, relatively few published simulation studies are multicenter in nature.
      Multicenter research confers many distinct advantages over single-center studies,
      including larger sample sizes for more generalizable findings, sharing resources
      amongst collaborative sites, and promoting networking. Well-executed multicenter
      studies are more likely to improve provider performance and/or have a positive
      impact on patient outcomes. In this manuscript, we offer a step-by-step guide to
      conducting multicenter, simulation-based research based upon our collective
      experience with the International Network for Simulation-based Pediatric
      Innovation, Research and Education (INSPIRE). Like multicenter clinical research,
      simulation-based multicenter research can be divided into four distinct phases.
      Each phase has specific differences when applied to simulation research: (1)
      Planning phase, to define the research question, systematically review the
      literature, identify outcome measures, and conduct pilot studies to ensure
      feasibility and estimate power; (2) Project Development phase, when the primary
      investigator identifies collaborators, develops the protocol and research
      operations manual, prepares grant applications, obtains ethical approval and
      executes subsite contracts, registers the study in a clinical trial registry,
      forms a manuscript oversight committee, and conducts feasibility testing and data
      validation at each site; (3) Study Execution phase, involving recruitment and
      enrollment of subjects, clear communication and decision-making, quality
      assurance measures and data abstraction, validation, and analysis; and (4)
      Dissemination phase, where the research team shares results via conference
      presentations, publications, traditional media, social media, and implements
      strategies for translating results to practice. With this manuscript, we provide
      a guide to conducting quantitative multicenter research with a focus on
      simulation-specific issues.

PMID- 29450008
TI  - The effects of active (hot-seat) versus observer roles during simulation-based
      training on stress levels and non-technical performance: a randomized trial.
AB  - Background: Active 'hands-on' participation in the 'hot-seat' during immersive
      simulation-based training (SBT) induces stress for participants, which is
      believed to be necessary to improve performance. We hypothesized that observers
      of SBT can subsequently achieve an equivalent level of non-technical performance
      as 'hot-seat' participants despite experiencing lower stress. Methods: We
      randomized 37 anaesthesia trainees into two groups to undergo three consecutive
      SBT scenarios. Eighteen 'hot-seat' trainees actively participated in all three
      scenarios, and 19 'observer' trainees were directed to observe the first two
      scenarios and participated in the 'hot-seat' only in scenario 3. Salivary
      cortisol (SC) was measured at four time points during each scenario. Primary
      endpoint for stress response was the change in SC (DeltaSC) from baseline.
      Performance was measured using the Anaesthetist's Non-Technical Skills (ANTS)
      Score. Results: Mean SC increased in all participants whenever they were in the
      'hot-seat' role, but not when in the observer role. Hot-seat DeltaSC (mcg/dL) for
      scenarios 1, 2, and 3 were 0.122 (p = 0.001), 0.074 (p = 0.047), and 0.085 (p =
      0.023), respectively. Observers DeltaSC (mcg/dL) for scenarios 1, 2, and 3 were 
      0.062 (p = 0.091), 0.010 (p = 0.780), and 0.144 (p = 0.001), respectively. Mean
      ANTS scores were equivalent between the 'hot-seat' (40.0) and 'observer' (39.4)
      groups in scenario 3 (p = 0.733). Conclusions: Observers of SBT achieved an
      equivalent level of non-technical performance, while experiencing lower stress
      than trainees repeatedly trained in the 'hot-seat'. Our findings suggest that
      directed observers may benefit from immersive SBT even without repeated 'hands
      on' experience and stress in the hot-seat. The directed observer role may offer a
      less stressful, practical alternative to the traditional 'hot-seat' role,
      potentially rendering SBT accessible to a wider audience. Trial registration:
      ClinicalTrials.gov Identifier NCT02211378, registered August 5, 2014,
      retrospectively registered.

PMID- 29450009
TI  - Students' understanding of teamwork and professional roles after
      interprofessional simulation-a qualitative analysis.
AB  - Background: This study explores how interprofessional simulation-based education
      (IPSE) can contribute to a change in students' understanding of teamwork and
      professional roles. A series of 1-day training sessions was arranged involving
      undergraduate nursing and medical students. Scenarios were designed for
      practicing teamwork principles and interprofessional communication skills by
      endorsing active participation by all team members. Methods: Four focus groups
      occurred 2-4 weeks after the training. Thematic analysis of the transcribed focus
      groups was applied, guided by questions on what changes in students'
      understanding of teamwork and professional roles were identified and how such
      changes had been achieved. Results: The first question, aiming to identify
      changes in students' understanding of teamwork, resulted in three categories:
      realizing and embracing teamwork fundamentals, reconsidering professional roles,
      and achieving increased confidence. The second question, regarding how
      participation in IPSE could support the transformation of students' understanding
      of teamwork and of professional roles, embraced another three categories: feeling
      confident in the learning environment, embodying experiences, and obtaining an
      outside perspective. Conclusions: This study showed the potential of IPSE to
      transform students' understanding of others' professional roles and
      responsibilities. Students displayed extensive knowledge on fundamental teamwork
      principles and what these meant in the midst of participating in the scenarios. A
      critical prerequisite for the development of these new insights was to feel
      confident in the learning environment. The significance of how the environment
      was set up calls for further research on the design of IPSE in influencing role
      understanding and communicative skills in significant ways.

PMID- 29450010
TI  - An institution-wide approach to submission, review, and funding of simulation
      based curricula.
AB  - This article describes the development, implementation, and modification of an
      institutional process to evaluate and fund graduate medical education simulation
      curricula. The goals of this activity were to (a) establish a standardized
      mechanism for proposal submission and evaluation, (b) identify simulation-based
      medical education (SBME) curricula that would benefit from mentored improvement
      before implementation, and (c) ensure that funding decisions were fair and
      defensible. Our intent was to develop a process that was grounded in sound
      educational principles, allowed for efficient administrative oversight, ensured
      approved courses were high quality, encouraged simulation education research and
      scholarship, and provided opportunities for medical specialties that had not
      previously used SBME to receive mentoring and faculty development.

PMID- 29450011
TI  - The Association of Standardized Patient Educators (ASPE) Standards of Best
      Practice (SOBP).
AB  - In this paper, we define the Association of Standardized Patient Educators (ASPE)
      Standards of Best Practice (SOBP) for those working with human role players who
      interact with learners in a wide range of experiential learning and assessment
      contexts. These human role players are variously described by such terms as
      standardized/simulated patients or simulated participants (SP or SPs). ASPE is a
      global organization whose mission is to share advances in SP-based pedagogy,
      assessment, research, and scholarship as well as support the professional
      development of its members. The SOBP are intended to be used in conjunction with
      the International Nursing Association for Clinical Simulation and Learning
      (INACSL) Standards of Best Practice: SimulationSM, which address broader
      simulation practices. We begin by providing a rationale for the creation of the
      ASPE SOBP, noting that with the increasing use of simulation in healthcare
      training, it is incumbent on ASPE to establish SOBP that ensure the growth,
      integrity, and safe application of SP-based educational endeavors. We then
      describe the three and a half year process through which these standards were
      developed by a consensus of international experts in the field. Key terms used
      throughout the document are defined. Five underlying values inform the SOBP:
      safety, quality, professionalism, accountability, and collaboration. Finally, we
      describe five domains of best practice: safe work environment; case development;
      SP training for role portrayal, feedback, and completion of assessment
      instruments; program management; and professional development. Each domain is
      divided into principles with accompanying key practices that provide clear and
      practical guidelines for achieving desired outcomes and creating simulations that
      are safe for all stakeholders. Failure to follow the ASPE SOBP could compromise
      the safety of participants and the effectiveness of a simulation session. Care
      has been taken to make these guidelines precise yet flexible enough to address
      the diversity of varying contexts of SP practice. As a living document, these
      SOBP will be reviewed and modified periodically under the direction of the ASPE
      Standards of Practice Committee as SP methodology grows and adapts to evolving
      simulation practices.

PMID- 29450012
TI  - Cumulative evaluation data: pediatric airway management simulation courses for
      pediatric residents.
AB  - Objectives: To utilize cumulative evaluation data of the pediatric airway
      management simulation-based learning course on knowledge and practical skills of
      residents in the Saudi Commission for Health Speciality (SCFHS) in order to
      measure its efficacy and areas for improvement. Methods: The evaluation is a
      retrospective cohort study that compares pre- and post-test (knowledge and
      skills) of a pediatric airway management simulation course. The 2-day course has
      been conducted four times annually at CRESENT and is comprised of interactive
      lectures on airway management and crew resource management, a demonstration of
      fundamentals of intubation, three skill stations, and six case scenarios with
      debriefing. Our evaluation data includes all pediatric residents who attended the
      course between January and December 2015. Results: Forty-six residents
      participated, of whom 30 (65.2%) are male and 16 (34.78%) are female. Overall,
      there is statistically significant improvement between the pre-test and post-test
      knowledge and practical skill scores. The pre-test scores are significantly
      different between the four different resident levels with p values of 0.003 and
      <0.001 respectively. However, there are no statistically significant differences
      in the post-test scores among the four different resident levels with p values of
      0.372 and 0.133 respectively. The practical skill assessment covers four main
      domains. Improvements were noted in pharmacology (811%), equipment setup (250%),
      intubation steps (200%), and patient positioning (130%). The post-test scores are
      similar in all practical skill categories for the four different residency
      levels. Discussion: Our outcome-based evaluation strategy demonstrated that
      residents met the course learning objectives. The pediatric airway management
      simulation course at CRESENT is effective in improving the knowledge and
      practical skills of pediatric residents. Although the greatest improvement is
      noted among junior residents, learners from different residency levels have
      comparable knowledge and practical skills at the end of the course. Things that
      can be improved based on our study results include stressing more the type and
      dosages of the medications used in airway management and mandating the course for
      all junior pediatric residents. Although residents scored well, specific
      knowledge and skill elements still led us to targeted areas for course
      excellence. Similar courses need to be integrated in the pediatric residency
      curriculum. Further research is needed to study skill retention and more
      importantly its impact on patients' care. Although resource-intensive, the use of
      cumulative evaluation data helped to focus quality improvement in our courses.

PMID- 29450013
TI  - Early acquisition of non-technical skills using a blended approach to simulation
      based medical education.
AB  - Background: Non-technical skills are emerging as an important component of
      postgraduate medical education. Between 2013 and 2016, a new blended training
      program incorporating non-technical skills was introduced at an Australian
      university affiliated hospital. Program participants were medical officers in
      years 1 and 2 of postgraduate training. Methods: An interdisciplinary faculty
      trained in simulation-based education led the program. The blended approach
      combined open access online resources with multiple opportunities to participate
      in simulation-based learning. The aim of the study was to examine the value of
      the program to the participants and the effects on the wider hospital system. The
      mixed methods evaluation included data from simulation centre records, hospital
      quality improvement data, and a post-hoc reflective survey of the enrolled
      participants (n = 68). Results: Over 30 months, 283 junior doctors were invited
      to participate in the program. Enrolment in a designated simulation-based course
      was completed by 169 doctors (59.7%). Supplementary revision sessions were made
      available to the cohort with a median weekly attendance of five participants.
      56/68 (82.4%) of survey respondents reported increased confidence in managing
      deteriorating patients. During the period of implementation, the overall rate of
      hospital cardiac arrests declined by 42.3%. Future objectives requested by
      participants included training in graded assertiveness and neurological
      emergencies. Conclusions: Implementation of a non-technical skills program was
      achieved with limited simulation resources and was associated with observable
      improvements in clinical performance. The participants surveyed reported
      increased confidence in managing deteriorating patients, and the program
      introduction coincided with a significant reduction in the rate of in-hospital
      cardiac arrests.

PMID- 29450014
TI  - A simulated "Night-onCall" to assess and address the readiness-for-internship of
      transitioning medical students.
AB  - Transitioning medical students are anxious about their readiness-for-internship,
      as are their residency program directors and teaching hospital leadership
      responsible for care quality and patient safety. A readiness-for-internship
      assessment program could contribute to ensuring optimal quality and safety and be
      a key element in implementing competency-based, time-variable medical education.
      In this paper, we describe the development of the Night-onCall program (NOC), a 4
      h readiness-for-internship multi-instructional method simulation event. NOC was
      designed and implemented over the course of 3 years to provide an authentic
      "night on call" experience for near graduating students and build measurements of
      students' readiness for this transition framed by the Association of American
      Medical College's Core Entrustable Professional Activities for Entering
      Residency. The NOC is a product of a program of research focused on questions
      related to enabling individualized pathways through medical training. The lessons
      learned and modifications made to create a feasible, acceptable, flexible, and
      educationally rich NOC are shared to inform the discussion about transition to
      residency curriculum and best practices regarding educational handoffs from
      undergraduate to graduate education.

PMID- 29450015
TI  - Tracing the prescription journey: a qualitative evaluation of an
      interprofessional simulation-based learning activity.
AB  - Background: In many countries across the world, the majority of prescribing
      occurs within the community setting. Close collaboration between general
      practitioners (GPs) and pharmacists is required to ensure effective therapeutic
      treatment of patients, whilst minimising prescribing and dispensing errors.
      Despite the need to work collaboratively, medical and pharmacy training is often
      unilateral. Interprofessional education (IPE) and simulation-based education
      (SBE) are teaching approaches widely used by healthcare professionals to foster
      collaborative practice. At Queen's University Belfast (QUB), an innovative IPE
      activity was developed for medical and pharmacy undergraduate students that aimed
      to develop a greater understanding of their roles and duties in community
      prescribing and dispensing. This study set out to evaluate the impact of such a
      SBE activity on students' attitudes towards collaborative practice in prescribing
      and dispensing medication in the community. Methods: Interprofessional groups of
      year 3 pharmacy (n = 10) and year 4 medical (n = 9) students took part in a SBE
      activity. This focused on the IPE team clinically assessing, diagnosing, writing
      prescriptions, dispensing medication(s) and counselling a simulated patient (in a
      simulated practice and pharmacy setting). Using a questioning guide, four focus
      groups of medical and pharmacy students were used to evaluate their attitudes
      towards the simulated IPE activity. Interviews were audio-recorded, transcribed
      and analysed iteratively using thematic analysis. Results: Four main themes
      emerged from the analysis: (1) IPE simulation activity: creating a broader
      learning experience; (2) patient-centred practice: a shared understanding; (3)
      professional skills: explored and shared; and (4) professional roles: a journey
      of discovery, respect and stereotypes. Conclusions: Students broadened their
      knowledge of each other's expertise in skills and clinical roles whilst working
      together. Furthermore, students valued the opportunity to strengthen cooperation
      with their future colleagues with the shared goal of improving patient-centred
      care.

PMID- 29450016
TI  - Simulation in the clinical setting: towards a standard lexicon.
AB  - Simulation-based educational activities are happening in the clinical environment
      but are not all uniform in terms of their objectives, delivery, or outputs. While
      these activities all provide an opportunity for individual and team training,
      nuances in the location, timing, notification, and participants impact the
      potential outcomes of these sessions and objectives achieved. In light of this,
      there are actually many different types of simulation-based activity that occur
      in the clinical environment, which has previously all been grouped together as
      "in situ" simulation. However, what truly defines in situ simulation is how the
      clinical environment responds in its' natural state, including the personnel,
      equipment, and systems responsible for care in that environment. Beyond
      individual and team skill sets, there are threats to patient safety or quality
      patient care that result from challenges with equipment, processes, or system
      breakdowns. These have been labeled "latent safety threats." We submit that the
      opportunity for discovery of latent safety threats is what defines in situ
      simulation and truly differentiates it from what would be more rightfully called
      "on-site" simulation. The distinction between the two is highlighted in this
      article, as well as some of the various sub-types of in situ simulation.

PMID- 29450017
TI  - Distributed Simulation as a modelling tool for the development of a simulation
      based training programme for cardiovascular specialties.
AB  - Aims and background: Distributed Simulation is the concept of portable, high
      fidelity immersive simulation. Here, it is used for the development of a
      simulation-based training programme for cardiovascular specialities. We present
      an evidence base for how accessible, portable and self-contained simulated
      environments can be effectively utilised for the modelling, development and
      testing of a complex training framework and assessment methodology. Iterative
      user feedback through mixed-methods evaluation techniques resulted in the
      implementation of the training programme. Approach: Four phases were involved in
      the development of our immersive simulation-based training programme: (1) initial
      conceptual stage for mapping structural criteria and parameters of the simulation
      training framework and scenario development (n = 16), (2) training facility
      design using Distributed Simulation, (3) test cases with clinicians (n = 8) and
      collaborative design, where evaluation and user feedback involved a mixed-methods
      approach featuring (a) quantitative surveys to evaluate the realism and perceived
      educational relevance of the simulation format and framework for training and (b)
      qualitative semi-structured interviews to capture detailed feedback including
      changes and scope for development. Refinements were made iteratively to the
      simulation framework based on user feedback, resulting in (4) transition towards
      implementation of the simulation training framework, involving consistent
      quantitative evaluation techniques for clinicians (n = 62). For comparative
      purposes, clinicians' initial quantitative mean evaluation scores for realism of
      the simulation training framework, realism of the training facility and relevance
      for training (n = 8) are presented longitudinally, alongside feedback throughout
      the development stages from concept to delivery, including the implementation
      stage (n = 62). Findings: Initially, mean evaluation scores fluctuated from low
      to average, rising incrementally. This corresponded with the qualitative
      component, which augmented the quantitative findings; trainees' user feedback was
      used to perform iterative refinements to the simulation design and components
      (collaborative design), resulting in higher mean evaluation scores leading up to
      the implementation phase. Conclusions: Through application of innovative
      Distributed Simulation techniques, collaborative design, and consistent
      evaluation techniques from conceptual, development, and implementation stages,
      fully immersive simulation techniques for cardiovascular specialities are
      achievable and have the potential to be implemented more broadly.

PMID- 29450018
TI  - Implementing simulation in a nursing education programme: a case report from
      Tanzania.
AB  - This paper presents a description of, and some reflections around, the experience
      of implementing simulation-based education within a nursing education programme
      in a low-income context. The students in the nursing education programme found
      the simulation sessions to be useful, motivating and a realistic learning method.
      Our experience may provide useful insight for other nursing education programmes
      in low-income contexts. It looks like a deeper knowledge about the feasibility of
      simulation-based education from both the teacher and student perspective is
      necessary.

PMID- 29450019
TI  - Creating a quality improvement culture in standardized/simulated patient
      methodology: the role of professional societies.

PMID- 29450020
TI  - Documentation framework for healthcare simulation quality improvement activities.

PMID- 29450021
TI  - Translational simulation: not 'where?' but 'why?' A functional view of in situ
      simulation.
AB  - Healthcare simulation has been widely adopted for health professional education
      at all stages of training and practice and across cognitive, procedural,
      communication and teamwork domains. Recent enthusiasm for in situ simulation
      delivered in the real clinical environment-cites improved transfer of knowledge
      and skills into real-world practice, as well as opportunities to identify latent
      safety threats and other workplace-specific issues. However, describing
      simulation type according to place may not be helpful. Instead, I propose the
      term translational simulation as a functional term for how simulation may be
      connected directly with health service priorities and patient outcomes, through
      interventional and diagnostic functions, independent of the location of the
      simulation activity.

PMID- 29450022
TI  - Variation and adaptation: learning from success in patient safety-oriented
      simulation training.
AB  - Simulation is traditionally used to reduce errors and their negative
      consequences. But according to modern safety theories, this focus overlooks the
      learning potential of the positive performance, which is much more common than
      errors. Therefore, a supplementary approach to simulation is needed to unfold its
      full potential. In our commentary, we describe the learning from success (LFS)
      approach to simulation and debriefing. Drawing on several theoretical frameworks,
      we suggest supplementing the widespread deficit-oriented, corrective approach to
      simulation with an approach that focusses on systematically understanding how
      good performance is produced in frequent (mundane) simulation scenarios. We
      advocate to investigate and optimize human activity based on the connected layers
      of any setting: the embodied competences of the healthcare professionals, the
      social and organizational rules that guide their actions, and the material
      aspects of the setting. We discuss implications of these theoretical perspectives
      for the design and conduct of simulation scenarios, post-simulation debriefings,
      and faculty development programs.

PMID- 29450023
TI  - Reducing the impact of intensive care unit mattress compressibility during CPR: a
      simulation-based study.
AB  - Background: The depth of chest compression (CC) during cardiac arrest is
      associated with patient survival and good neurological outcomes. Previous studies
      showed that mattress compression can alter the amount of CCs given with adequate
      depth. We aim to quantify the amount of mattress compressibility on two types of
      ICU mattresses and explore the effect of memory foam mattress use and a backboard
      on mattress compression depth and effect of feedback source on effective
      compression depth. Methods: The study utilizes a cross-sectional self-control
      study design. Participants working in the pediatric intensive care unit (PICU)
      performed 1 min of CC on a manikin in each of the following four conditions: (i)
      typical ICU mattress; (ii) typical ICU mattress with a CPR backboard; (iii)
      memory foam ICU mattress; and (iv) memory foam ICU mattress with a CPR backboard,
      using two different sources of real-time feedback: (a) external accelerometer
      sensor device measuring total compression depth and (b) internal light sensor
      measuring effective compression depth only. CPR quality was concurrently measured
      by these two devices. The differences of the two measures (mattress compression
      depth) were summarized and compared using multilevel linear regression models.
      Effective compression depths with different sources of feedback were compared
      with a multilevel linear regression model. Results: The mean mattress compression
      depth varied from 24.6 to 47.7 mm, with percentage of depletion from 31.2 to
      47.5%. Both use of memory foam mattress (mean difference, MD 11.7 mm, 95%CI 4.8
      18.5 mm) and use of backboard (MD 11.6 mm, 95% CI 9.0-14.3 mm) significantly
      minimized the mattress compressibility. Use of internal light sensor as source of
      feedback improved effective CC depth by 7-14 mm, compared with external
      accelerometer sensor. Conclusion: Use of a memory foam mattress and CPR backboard
      minimizes mattress compressibility, but depletion of compression depth is still
      substantial. A feedback device measuring sternum-to-spine displacement can
      significantly improve effective compression depth on a mattress. Trial
      registration: Not applicable. This is a mannequin-based simulation research.

PMID- 29450024
TI  - An activity theory perspective of how scenario-based simulations support
      learning: a descriptive analysis.
AB  - Background: The dominant frameworks for describing how simulations support
      learning emphasize increasing access to structured practice and the provision of
      feedback which are commonly associated with skills-based simulations. By
      contrast, studies examining student participants' experiences during scenario
      based simulations suggest that learning may also occur through participation.
      However, studies directly examining student participation during scenario-based
      simulations are limited. This study examined the types of activities student
      participants engaged in during scenario-based simulations and then analyzed their
      patterns of activity to consider how participation may support learning. Methods:
      Drawing from Engestrom's first-, second-, and third-generation activity systems
      analysis, an in-depth descriptive analysis was conducted. The study drew from
      multiple qualitative methods, namely narrative, video, and activity systems
      analysis, to examine student participants' activities and interaction patterns
      across four video-recorded simulations depicting common motivations for using
      scenario-based simulations (e.g., communication, critical patient management).
      Results: The activity systems analysis revealed that student participants'
      activities encompassed three clinically relevant categories, including (a) use of
      physical clinical tools and artifacts, (b) social interactions, and (c)
      performance of structured interventions. Role assignment influenced participants'
      activities and the complexity of their engagement. Importantly, participants made
      sense of the clinical situation presented in the scenario by reflexively linking
      these three activities together. Specifically, student participants performed
      structured interventions, relying upon the use of physical tools, clinical
      artifacts, and social interactions together with interactions between students,
      standardized patients, and other simulated participants to achieve their goals.
      When multiple student participants were present, such as in a team-based
      scenario, they distributed the workload to achieve their goals. Conclusion: The
      findings suggest that student participants learned as they engaged in these
      scenario-based simulations when they worked to make sense of the patient's
      clinical presentation. The findings may provide insight into how student
      participants' meaning-making efforts are mediated by the cultural artifacts
      (e.g., physical clinical tools) they access, the social interactions they engage
      in, the structured interventions they perform, and the roles they are assigned.
      The findings also highlight the complex and emergent properties of scenario-based
      simulations as well as how activities are nested. Implications for learning,
      instructional design, and assessment are discussed.

PMID- 29450026
TI  - Method matters: impact of in-scenario instruction on simulation-based teamwork
      training.
AB  - Background: The rationale for introducing full-scale patient simulators in
      training to improve patient safety is to recreate clinical situations in a
      realistic setting. Although high-fidelity simulators mimic a wide range of human
      features, simulators differ from the body of a sick patient. The gap between the
      simulator and the human body implies a need for facilitators to provide
      information to help participants understand scenarios. The authors aimed at
      describing different methods that facilitators in our dataset used to provide
      such extra scenario information and how the different methods to convey
      information affected how scenarios played out. Methods: A descriptive qualitative
      study was conducted to examine the variation of methods to deliver extra scenario
      information to participants. A multistage approach was employed. The authors
      selected film clips from a shared database of 31 scenarios from three
      participating simulation centers. A multidisciplinary research team performed a
      collaborative analysis of representative film clips focusing on the interplay
      between participants, facilitators, and the physical environment. After that, the
      entire material was revisited to further examine and elaborate the initial
      findings. Results: The material displayed four distinct methods for facilitators
      to convey information to participants in simulation-based teamwork training. The
      choice of method had impact on the participating teams regarding flow of work,
      pace, and team communication. Facilitators' close access to the teams' activities
      when present in the simulation suite, either embodied or disembodied in the
      simulation, facilitated the timing for providing information, which was critical
      for maintaining the flow of activities in the scenario. The mediation of
      information by a loudspeaker or an earpiece from the adjacent operator room could
      be disturbing for team communication. Conclusions: In-scenario instruction is an
      essential component of simulation-based teamwork training that has been largely
      overlooked in previous research. The ways in which facilitators convey
      information about the simulated patient have the potential to shape the
      simulation activities and thereby serve different learning goals. Although
      immediate timing to maintain an adequate pace is necessary for professionals to
      engage in training of medical emergencies, novices may gain from a slower tempo
      to train complex clinical team tasks systematically.

PMID- 29450025
TI  - Improving the quality of transvaginal ultrasound scan by simulation training for
      general practice residents.
AB  - Background: Ultrasonography (US) is an essential tool for the diagnosis of acute
      gynecological conditions. General practice (GP) residents are involved in the
      first-line management of gynecologic emergencies. They are not familiar with US
      equipment. Initial training on simulators was conducted.The aim of this study was
      to evaluate the impact of simulation-based training on the quality of the
      sonographic images achieved by GP residents 2 months after the simulation
      training versus clinical training alone. Methods: Young GP residents assigned to
      emergency gynecology departments were invited to a one-day simulation-based US
      training session. A prospective controlled trial aiming to assess the impact of
      such training on TVS (transvaginal ultrasound scan) image quality was conducted.
      The first group included GP residents who attended the simulation training
      course. The second group included GP residents who did not attend the course.
      Written consent to participate was obtained from all participants. Images
      achieved 2 months after the training were scored using standardized quality
      criteria and compared in both groups. The stress generated by this examination
      was also assessed with a simple numeric scale. Results: A total of 137 residents
      attended the simulation training, 26 consented to participate in the controlled
      trial. Sonographic image quality was significantly better in the simulation group
      for the sagittal view of the uterus (3.6 vs 2.7, p = 0.01), for the longitudinal
      view of the right ovary (2.8 vs 1.4, p = 0.027), and for the Morrison space (1.7
      vs 0.4, p = 0.034), but the difference was not significant for the left ovary
      (2.9 vs 1.7, p = 0.189). The stress generated by TVS after 2 months was not
      different between the groups (6.0 vs 4.8, p = 0.4). Conclusion: Simulation-based
      training improved the quality of pelvic US images in GP residents assessed after
      2 months of experience in gynecology compared to clinical training alone.

PMID- 29450028
TI  - Implementation of a novel synchronous multi-site all day high-fidelity
      simulation.
AB  - Integration of simulation in educational curricula for anesthesia and intensive
      care residents is a hot topic. There is a great interest for simulation centers
      to share their experiences through multi-site synchronous simulation sessions.
      The present study results from an experience conducted at three sites in France
      (Paris, Lyon, and Caen), which involved 16 instructors and 25 residents facing
      the same scenario across 1 day. Synchronous simulations were performed at each
      site with local and shared debriefing via teleconference. This innovative
      approach to simulation was found to be feasible, although certain difficulties
      were encountered with connectivity.

PMID- 29450027
TI  - Faculty development through simulation-based education in physical therapist
      education.
AB  - Background: The use of simulation-based education (SBE) in health professions,
      such as physical therapy, requires faculty to expand their teaching practice and
      development. The impact of this teaching on the individual faculty member, and
      how their teaching process changes or develops, is not fully understood. The
      purpose of this study was to explore individual physical therapist faculty
      members' experience with SBE and how those experiences may have transformed their
      teaching practice to answer the research questions: How do physical therapist
      faculty develop through including SBE and are there commonalities among
      educators? Methods: An interpretive phenomenological analysis approach was used
      with a small sample of subjects who participated in three individual semi
      structured interviews. Interview questions were created through the lens of
      transformative learning theory to allow faculty transformations to be uncovered.
      A two-step thematic coding process was conducted across participants to identify
      commonalities of faculty experiences with SBE in physical therapist education.
      Credibility and trustworthiness were achieved through member checking and expert
      external review. Thematic findings were validated with transcript excerpts and
      research field notes. Results: Eight physical therapist faculty members (25%
      male) with a range of 3 to 16 years of incorporating SBE shared their individual
      experiences. Four common themes related to faculty development were identified
      across the participants. Themes identified are the following: faculty strengthen
      their professional identity as physical therapists, faculty are affected by their
      introduction and training with simulation, faculty develop their
      interprofessional education through SBE, and faculty experiences with SBE
      facilitate professional growth. Conclusion: Physical therapist educators had
      similarities in their experiences with SBE that transformed their teaching
      practice and professional development. This study provides insight into what
      physical therapist faculty may experience when adopting SBE.

PMID- 29450029
TI  - Preface: a new stage in the evolution of public health reviews.

PMID- 29450030
TI  - Foundational values for public health.
AB  - The development of an agreed-upon set of foundational ethical values for the
      field of public health is ongoing. In this paper we outline key elements of
      recent convergence on some basic moral precepts that drive public health. We
      suggest that three elements are particularly useful for anchoring public health
      practitioners' reflections on public health ethics: 1) the notions of "common"
      and "professional" morality, 2) an understanding of the practice and content of
      modern public health and especially its practical, solution-focused orientation,
      and 3) an appreciation of the history of public health as integrally linked to
      evolving and contested views of the relationship between citizens, science, and
      the state. There is broad agreement that governments are stewards of their
      populations and are responsible for providing conditions that allow for its
      members to be healthy and productive. Given the role of policy and government in
      public health, the role of political philosophy likely has a substantial place as
      we seek a coherent system of ethical justification in our work. The aim here is
      not to align with one theoretical approach or another, rather, to consider the
      foundational values of public health practice order to identify the common moral
      governance of our work. Our profession's morality-the set of norms shared by all
      public health professionals-is determined by what public health is and what we
      think it should be. As our aspirations for public health evolve, it is incumbent
      upon us to engage in reflective discourse to reach a new equilibrium about our
      moral foundation.

PMID- 29450031
TI  - Towards public health ethics.
AB  - Health is a value, both objective and subjective, yet it is not the only value
      that contributes to the well-being of persons. In public health, there are
      different connotations of the term "public" relevant from an ethical perspective:
      population, government action, and collective action of the community. Ethics
      seeks to provide a basis for and justify moral decisions and actions. Ethics
      asks, why should I do it?, and the reply consists of an argument. The type of
      ethics that underpins applied ethics in general, and bioethics in particular, is
      civic ethics, a philosophical reflection on the criteria that enable the peaceful
      coexistence of citizens with different morals. Progress means emancipation as
      well as an increase of autonomy. However, more is not always better, and now we
      know that no health intervention, including a public health intervention, is risk
      free. The false belief that undergoing a prevention intervention is always better
      than doing nothing explains, at least in part, that in contrast to bioethics,
      only recently have the ethical implications in public health practice been given
      the attention they deserve. Positive externalities in third parties, such as in
      vaccination programmes or policies to prevent harm to passive smokers, can
      occasionally justify the potential risks of a public health intervention. It is
      in such situations where a conflict might arise between the goal of improving the
      health of the population and the respect for the rights and freedoms of the
      individual that characterizes the dilemmas in public health ethics. In
      conclusion, it is necessary to have a public health ethics framework and a
      professional code of ethics applied to public health. The training of public
      health professionals in ethics is essential to ensure that they feel more
      confident when it comes to addressing the sheer range of ethical conflicts that
      they frequently face in the performance of their duties.

PMID- 29450032
TI  - Integrating ethics in public health education: the process of developing case
      studies.
AB  - The study of ethics in public health became a societal imperative following the
      horrors of pre World War II eugenics, the Holocaust, and the Tuskegee Experiment
      (and more recent similar travesties). International responses led to: the
      Nuremberg Doctors' Trials, the Universal Declaration of Human Rights (1948), and
      the Convention on Prevention and Punishment of the Crime of Genocide (CCPCG,
      1948), which includes sanctions against incitement to genocide. The Declaration
      of Geneva (1948) set forth the physician's dedication to the humanitarian goals
      of medicine, a declaration especially important in view of the medical crimes
      which had just been committed in Nazi Germany. This led to a modern revision of
      the Hippocratic Oath in the form of the Declaration of Helsinki (1964) for
      medical research ethical standards, which has been renewed periodically and
      adopted worldwide to ensure ethical research practices. Public health ethics
      differs from traditional biomedical ethics in many respects, specifically in its
      emphasis on societal considerations of prevention, equity, and population-level
      issues. Health care systems are increasingly faced with the need to integrate
      clinical medicine with public health and health policy. As health systems and
      public health evolve, the ethical issues in health care also bridge the gap
      between the separation of bioethics and public health ethics in the past. These
      complexities calls for the inclusion of ethics in public health education
      curricula and competencies across the many professions in public health, in the
      policy arena, as well as educational engagement with the public and the lay
      communities and other stakeholders.

PMID- 29450033
TI  - Continuing the conversation about public health ethics: education for public
      health professionals in Europe.

PMID- 29450034
TI  - An ethics training specific for European public health.
AB  - Training in public health ethics is not at the core of public health programmes
      in Europe. The fruitful progress of the United States could stimulate the
      European schools of public health and other academic institutions to develop
      specifically European teaching programmes for ethics that embrace both
      transatlantic innovations and some adaptations based on the evolution of moral
      values in European societies. This paper reviews the arguments for a European
      public health ethics curriculum and recommends the main features of such a
      programme. Europe shares common values and, above all, the three major ethical
      principles that were socially and politically crystallized by the French
      Revolution: liberty, equality, and fraternity. Fraternity, otherwise known as
      solidarity, although rarely mentioned in the literature on ethical issues, is the
      moral value that best defines the European concept of public health expressed as
      a common good, mutual aid, and a collective or shared responsibility for health
      of the population. Specific political motivations were responsible for the origin
      of European health systems and for current policy proposals led by the European
      Union, such as Europe's commitments, at least in theory, to: reduce social
      inequities in health and to develop the health in all policies approach. These
      and other initiatives, albeit not exclusively European, have political and legal
      repercussions that pose unique ethical challenges. Europe combines homogeneity in
      social determinants of health with heterogeneity in public health approaches and
      interventions. It is therefore necessary to develop training in ethics and good
      government for all public health workers in Europe, especially since a large
      segment of the population's health depends on actions and decisions adopted by
      the European Commission and its regulatory agencies as well as for non EU
      European Region countries. Based on these arguments, the paper concludes with
      several recommendations for a common nucleus for the ethics curriculum in Europe.

PMID- 29450035
TI  - Developing public health ethics learning modules - can we learn from critical
      pedagogy?
AB  - Curriculum development in masters of public health programs that effectively
      meets the complex ethical challenges of the 21st century is an important part of
      public health education and requires ethical reasoning and purposively thinking.
      Current master programs in Public Health do not regularly include modules in
      public health ethics. The aim of this paper is to present background and
      theoretical foundation for developing a methodology and methods to develop public
      health ethics modules for curriculum development in public health programs. We
      describe ethical reasoning in medicine and in Public Health, specify pedagogical
      approaches and key assignments organized around the critical pedagogy.

PMID- 29450036
TI  - Screening and overdiagnosis: public health implications.
AB  - Overdiagnosis is the diagnosis of an abnormality that bears no substantial health
      hazard and no benefit for patients to be aware of. Resulting mainly from the use
      of increasingly sensitive screening and diagnostic tests, as well as broadened
      definitions of conditions requiring an intervention, overdiagnosis is a growing
      but still largely misunderstood public health issue. Fear of missing a diagnosis
      or of litigation, financial incentives or patient's need of reassurance are
      further causes of overdiagnosis. The main consequence of overdiagnosis is
      overtreatment. Treating an overdiagnosed condition bears no benefit but can cause
      harms and generates costs. Overtreatment also diverts health professionals from
      caring for those most severely ill. Recognition of overdiagnosis due to screening
      is challenging since it is rarely identifiable at the individual level and
      difficult to quantify precisely at the population level. Overdiagnosis exists
      even for screening of proven efficacy and efficiency. Measures to reduce
      overdiagnosis due to screening include heightened sensitization of health
      professionals and patients, active surveillance and deferred treatment until
      early signs of disease progression and prognosis estimation through biomarkers
      (including molecular) profiling. Targeted screening and balanced information on
      its risk and benefits would also help limit overdiagnosis. Research is needed to
      assess the public health burden and implications of overdiagnosis due to
      screening activity.

PMID- 29450037
TI  - Screening for cardiovascular disease risk factors beginning in childhood.
AB  - Cardiovascular diseases (CVD) are the leading cause of death worldwide.
      Individual detection and intervention on CVD risk factors and behaviors
      throughout childhood and adolescence has been advocated as a strategy to reduce
      CVD risk in adulthood. The U.S. National Heart, Lung, and Blood Institute (NHLBI)
      has recently recommended universal screening of several risk factors in children
      and adolescents, at odds with several recommendations of the U.S. Services Task
      Force and of the U.K. National Screening committee. In the current review, we
      discuss the goals of screening for CVD risk factors (elevated blood pressure,
      abnormal blood lipids, diabetes) and behaviors (smoking) in children and appraise
      critically various screening recommendations. Our review suggests that there is
      no compelling evidence to recommend universal screening for elevated blood
      pressure, abnormal blood lipids, abnormal blood glucose, or smoking in children
      and adolescents. Targeted screening of these risk factors could be useful but
      specific screening strategies have to be evaluated. Research is needed to
      identify target populations, screening frequency, intervention, and follow-up.
      Meanwhile, efforts should rather focus on the primordial prevention of CVD risk
      factors and at maintaining a lifelong ideal cardiovascular health through
      environmental, policy, and educational approaches.

PMID- 29450038
TI  - Why and how would we implement a lung cancer screening program?
AB  - For decades, lung cancer has been the most common cancer in terms of both
      incidence and mortality. There has been very little improvement in the prognosis
      of lung cancer. Early treatment following early diagnosis is considered to have
      potential for development. The National Lung Screening Trial (NLST), a large,
      well-designed randomized controlled trial, evaluated low-dose computed tomography
      (LDCT) as a screening tool for lung cancer. Compared with chest X-ray, annual
      LDCT screening reduced death from lung cancer and overall mortality by 20 and 6.7
      %, respectively, in high-risk people aged 55-74 years. Several smaller trials of
      LDCT screening are under way, but none are sufficiently powered to detect a 20 %
      reduction in lung cancer death. Thus, it is very unlikely that the NLST results
      will be replicated. In addition, the NLST raises several issues related to
      screening, such as the high false-positive rate, overdiagnosis and cost.
      Healthcare providers and systems are now left with the question of whether the
      available findings should be translated into practice. We present the main
      reasons for implementing lung cancer screening in high-risk adults and discuss
      the main issues related to lung cancer screening. We stress the importance of
      eligibility criteria, smoking cessation programs, primary care physicians, and
      informed-decision making should lung cancer screening be implemented. Seven years
      ago, we were waiting for the results of trials. Such evidence is now available.
      Similar to almost all other cancer screens, uncertainties exist and persist even
      after recent scientific efforts and data. We believe that by staying within the
      characteristics of the original trial and appropriately sharing the evidence as
      well as the uncertainties, it is reasonable to implement a LDCT lung cancer
      screening program for smokers and former smokers.

PMID- 29450039
TI  - On the rationale of population screening for chronic kidney disease: a public
      health perspective.
AB  - Unlike opportunistic screening, population screening is accompanied by stringent
      quality control measures and careful programme monitoring. Sufficient evidence
      for benefit together with acceptable harms and costs to society are needed before
      launching a programme. A screening programme is a complex process organized at
      the population level involving multiple actors of the health care system that
      should ideally be supervised by public health authorities and evaluated by an
      independent and trustful body. Chronic kidney disease is defined by reduced
      glomerular filtration rate and/or presence of kidney damage for at least three
      months. Chronic kidney disease is divided into 5 stages with stages 1 to 3 being
      usually asymptomatic. Chronic kidney disease affects one in ten adults worldwide
      and its prevalence sharply increases with age. Kidney function is measured using
      serum creatinine-based, and/or cystatin C-based, equations. Markers of renal
      function show high intra-individual and inter-laboratory variabilities,
      highlighting the need for standardized procedures. There is also large inter
      individual variability in age-related kidney function decline. Despite these
      limitations, chronic kidney disease, as currently defined, has been consistently
      associated with high cardiovascular morbidity and mortality and high risk of end
      stage renal disease. Major modifiable risk factors for chronic kidney disease are
      diabetes, hypertension, obesity and cardiovascular disease. Several treatment
      options, ranging from antihypertensive and lipid-lowering treatments to dietary
      measures, reduce all-cause mortality and/or end-stage renal disease in patients
      with stages 1-3 chronic kidney disease. So far, no randomized controlled trial
      comparing outcomes with and without population screening for stages 1-3 chronic
      kidney disease has been published. Population screening for stages 1-3 chronic
      kidney disease is currently not recommended because of insufficient evidence for
      benefit. Given the current and future burden attributable to chronic kidney
      disease, randomized controlled trials exploring benefits and harms of population
      screening are clearly needed to prioritize resource allocations.

PMID- 29450040
TI  - Teaching public health ethics.
AB  - Teaching public health ethics has been recognised as patchy and somewhat
      theoretically incoherent for some years. Despite Beauchamp and Childress' work
      being widely known and used within health care its various principles have been
      criticised by a number of writers for, among other things, their inherent
      cultural relativism. This article suggests how a broader ethically oriented
      approach to the ever-changing field of public health might be pursued - so that a
      professional public health practitioner might be prepared for a lifelong career
      of ethical activism. Informed by the pedagogic philosophy of Freire it assumes
      the development of a module within an MPH programme. If, as is widely
      acknowledged, we are dealing with essentially a corpus of values, the challenge
      for an educator of public health ethics is how do we inculcate those values
      effectively and efficiently? How do we prepare students for as yet unrecognised
      ethical problems that they might confront? How do we assess such teaching? We
      know that even in clinical practice gaps appear between accepted ethical
      principles and actual practice. Within public health the conflicts generated by
      rival claimants and the contradictions of applying principles at a societal level
      become even clearer as action to control a situation might restrict the rights of
      others. This makes it even more important that students are exposed to learning
      experiences which will equip them adequately for a lifetime of practice.
      Traditional didactic approaches need to be supplemented with additional
      modalities such as case studies and role playing. Such case studies might
      encompass macro policy issues or micro operational issues. Other approaches could
      include citizen juries, examining international agreements and codes of practice,
      debates and encouraging explicit reflective practices. The importance of
      repetition, teachers as role models, courses which themselves demonstrate ethical
      practice, and a variety of methods are emphasized.

PMID- 29450041
TI  - Screening for cardiovascular disease risk and subsequent management in low and
      middle income countries: challenges and opportunities.
AB  - Background: Cardiovascular disease (CVD), mainly heart attack and stroke, is the
      leading cause of premature mortality in low and middle income countries (LMICs).
      Identifying and managing individuals at high risk of CVD is an important strategy
      to prevent and control CVD, in addition to multisectoral population-based
      interventions to reduce CVD risk factors in the entire population. Methods: We
      describe key public health considerations in identifying and managing individuals
      at high risk of CVD in LMICs. Results: A main objective of any strategy to
      identify individuals at high CVD risk is to maximize the number of CVD events
      averted while minimizing the numbers of individuals needing treatment. Scores
      estimating the total risk of CVD (e.g. ten-year risk of fatal and non-fatal CVD)
      are available for LMICs, and are based on the main CVD risk factors (history of
      CVD, age, sex, tobacco use, blood pressure, blood cholesterol and diabetes
      status). Opportunistic screening of CVD risk factors enables identification of
      persons with high CVD risk, but this strategy can be widely applied in low
      resource settings only if cost effective interventions are used (e.g. the WHO
      Package of Essential NCD interventions for primary health care in low resource
      settings package) and if treatment (generally for years) can be sustained,
      including continued availability of affordable medications and funding mechanisms
      that allow people to purchase medications without impoverishing them (e.g.
      universal access to health care). This also emphasises the need to re-orient
      health systems in LMICs towards chronic diseases management. Conclusion: The
      large burden of CVD in LMICs and the fact that persons with high CVD can be
      identified and managed along cost-effective interventions mean that health
      systems need to be structured in a way that encourages patient registration,
      opportunistic screening of CVD risk factors, efficient procedures for the
      management of chronic conditions (e.g. task sharing) and provision of affordable
      treatment for those with high CVD risk. The focus needs to be in primary care
      because that is where most of the population can access health care and because
      CVD programmes can be run effectively at this level.

PMID- 29450042
TI  - Prevalence of hypertension in Ethiopia: a systematic meta-analysis.
AB  - Background: Hypertension has been increasing in developing countries including
      Ethiopia. Other than smaller studies, there is no national prevalence study on
      hypertension in Ethiopia. These smaller studies reported varied prevalence of
      hypertension. This study is intended to summarize and pool the results of smaller
      region based studies to provide a national level estimate of the prevalence of
      hypertension. Methods: The studies were identified through internet search using
      the data base of MEDLINE/PubMed, Google scholar, EMBASE, HINARI, Cochrane library
      and reference lists of previous prevalence studies. We also made manual searches
      to identify relevant articles. Descriptive information for the original studies
      is presented in a table and the quantitative results were presented in forest
      plots. The Cochrane Q test and I2 test statistic were used to test heterogeneity
      across studies. The Pooled estimate of prevalence of hypertension was computed by
      a random effects model. Results: One hundred eight titles were identified through
      electronic searching using keywords. Of these, nine studies were meet the
      inclusion criteria. A random effect meta-analysis of the results from these 9
      studies was conducted to provide an estimate of the prevalence of hypertension in
      the Ethiopian population. The analysis showed that the prevalence of hypertension
      among Ethiopian population was estimated to be 19.6 % (95 % CI: 13.7 %, 25.5 %).
      Subgroup analyses indicated that the prevalence of hypertension is higher in the
      urban population (23.7 %) than rural and urban combined (14.7 %). The prevalence
      of hypertension among males (20.6 %) and females (19.2 %) was similar.
      Conclusion: This study found that the prevalence of hypertension in Ethiopia is
      increasing. This evidence suggests that attention has to be given to primary
      prevention of hypertension in the Ethiopian adult population, especially in the
      urban population by integrating it with health extension programs.

PMID- 29450043
TI  - Europe's collective failure to address the refugee crisis.
AB  - The European response to the refugee crisis has been lamentable. A preoccupation
      with numbers has, too often, ignored how each refugee is an individual, many of
      whom have experienced the most appalling conditions in their countries of origin
      and in transit. These stories are only rarely heard, when the cameras are there
      to capture the tragedies. In this commentary we review the challenges of
      responding to the health needs of refugees, including examples of best practice,
      but above all call for a concerted political response that will both reduce the
      pressure on refugees to flee conflict-afflicted countries and recognize their
      contribution if they do come to Europe.

PMID- 29450044
TI  - Creating conditions for Canadian aboriginal health equity: the promise of healthy
      public policy.
AB  - In the Canadian context, the persistence and growth of Aboriginal health and
      social inequity signals that we are at a critical public health policy juncture;
      current policy reflects an historic relationship between Aboriginal people and
      Canada that fails the contemporary health needs of Canada's Aboriginal peoples.
      In this review, we highlight the need for healthy public policy that recognizes
      and prioritizes the rights of Canada's Aboriginal people to achieve health
      equity. Drawing from a structural approach, we examine the historical scope and
      comprehensive breadth of the Indian Act in shaping modern Aboriginal health and
      social inequities. Canada's failure to implement a national public policy for
      Aboriginal health reflects the proliferation of racism in modern day Canada, and
      a distinctly lacking political will at the federal level. Despite these
      structural challenges, there is great promise in community self-determination in
      health care and the role of community-led research as advocacy for policy reform.
      In our conclusion, we turn to the Report on the Truth and Reconciliation
      Commission of Canada (2015) and draw upon the concept of reconciliation as a
      fundamental precursor for Aboriginal health equity. The burden of systemic change
      needed to promote healthy public policy cannot be carried by any single group of
      advocates; it is a shared responsibility that will require the collaboration and
      integration of various actors and knowledges.

PMID- 29450045
TI  - Nutritional rickets in immigrant and refugee children.
AB  - Immigrant and refugee populations bring public health challenges to host nations.
      In the current global refugee crisis, children are the most vulnerable
      subpopulation. Diseases that were considered rare in the host nation may be
      highly prevalent among immigrant children. The prevalence of nutritional rickets
      is increasing in high-income countries, largely driven by an influx of immigrant
      populations. Nutritional rickets is a bone disease in early childhood resulting
      in bone pain, delayed motor development, and bending of the bones, caused by
      vitamin D deficiency and/or inadequate dietary calcium intake. The consequences
      of nutritional rickets include stunted growth, developmental delay, lifelong bone
      deformities, seizures, cardiomyopathy, and even death. Nutritional rickets is
      most commonly seen in children from the Middle East, Africa, and South Asia in
      high-income countries. Dark skin pigmentation, sun avoidance, covering the skin,
      and prolonged breast feeding without vitamin D supplementation, are important
      risk factors for vitamin D deficiency, and combined with a lack of dairy products
      in the diet, these deficiencies can result in insufficient calcium supply for
      bone mineralization. We recommend screening all immigrant and refugee children
      under 5 years of age from these ethnic groups for nutritional rickets, based on
      clinical features, and confirming the diagnosis with radiographs of the wrists
      and knees. Because nutritional rickets is entirely preventable, public health
      policies must address the need for universal vitamin D supplementation and
      adequate dietary calcium to protect children from this scourge. Vitamin D
      supplementation of all infants and children with 400 IU/d during the first year
      of life and dietary or supplemental intakes of at least 600 IU/d of vitamin D and
      500 mg/d of calcium thereafter, will effectively prevent nutritional rickets. We
      call on national health authorities of host countries to implement health check
      lists and prevention programs that include screening for micronutrient
      deficiencies, in addition to assessing infections and vaccination programs. Due
      to their high prevalence of vitamin D deficiency, refugee children of all ages
      from these ethnic groups should be supplemented with vitamin D, beginning upon
      arrival.

PMID- 29450047
TI  - Access to healthcare for undocumented migrants in France: a critical examination
      of State Medical Assistance.
AB  - In France in 2012, of the total population of 65.2 million, 8.7 % were migrants.
      After being the third principal host country, France is now the 6th highest host
      country in the OECD. Since the 1980's numerous Acts have been passed by
      parliament on immigration issues. In 2000 the Universal Health Cover (Couverture
      Maladie Universelle) was created as health coverage for all residents of France.
      At the same time the State Medical Assistance (Aide Medicale de l'Etat) was
      created as health protection for undocumented migrants. Since the creation of
      this scheme, it has been the object of many political debates which call it into
      question, on account of its cost, perceived fraud, and the legitimacy of a social
      protection for undocumented migrants. Recently, access to State Medical
      Assistance has been made difficult by introducing conditions of residence and
      financial contributions. After a reports' analysis on institutional, associative,
      research studies and European recommendations, we note that all reports converge
      on the necessity of health protection for undocumented migrants. The major
      reasons are humanitarian, respect of European and International conventions, for
      public health, and financial. Moreover, fraud allegations have proved to be
      unfounded. Finally, State Medical Assistance is underused: in 2014 data from
      Medecins du Monde shows that only 10.2 % of undocumented migrant patients in
      their health facilities have access to this scheme. We conclude that the
      political debate concerning the State Medical Assistance should be about its
      under-utilisation, its improvement, its merger with the Universal Health Cover,
      and not its elimination. Moreover, the current debates regarding this scheme
      stigmatize this population, which is already precarious, making it more difficult
      for migrants to access healthcare, and generally, weaken national social
      cohesion.

PMID- 29450046
TI  - Social and health epidemiology of immigrants in Germany: past, present and
      future.
AB  - Germany has experienced different forms of immigration for many decades. At the
      end of and after the Second World War, refugees, displaced persons and German
      resettlers constituted the largest immigrant group. In the 1950s, labor migration
      started, followed by family reunification. There has been a constant migration of
      refugees and asylum seekers reaching peaks in the early 1990s as well as today.
      Epidemiological research has increasingly considered the health, and the access
      to health care, of immigrants and people with migration background. In this
      narrative review we discuss the current knowledge on health of immigrants in
      Germany. The paper is based on a selective literature research with a focus on
      studies using representative data from the health reporting system. Our review
      shows that immigrants in Germany do not suffer from different diseases than non
      immigrants, but they differ in their risk for certain diseases, in the resources
      to cope with theses risk and regarding access to treatment. We also identified
      the need for differentiation within the immigrant population, considering among
      others social and legal status, country of origin and duration of stay. Though
      most of the studies acknowledge the need for differentiation, the lack of data
      currently rules out analyses accounting for the existing diversity and thus a
      full understanding of health inequalities related to migration to Germany.

PMID- 29450048
TI  - The need for a rights-based public health approach to Australian asylum seeker
      health.
AB  - Public health professionals have a responsibility to protect and promote the
      right to health amongst populations, especially vulnerable and disenfranchised
      groups, such as people seeking asylum and whose health care is frequently
      compromised. As at 31 March 2016, there was a total of 3707 people (including 384
      children) in immigration detention facilities or community detention in
      Australia, with 431 of them detained for more than 2 years. The Public Health
      Association of Australia and the Australian Medical Association assert that
      people seeking asylum in Australia have a right to health in the same way as
      Australian citizens, and they denounce detention of such people in government
      facilities for prolonged and indeterminate periods of time. The position of these
      two professional organisations is consistent with the compelling body of evidence
      demonstrating the negative impact detention has on health. Yet in recent years,
      both the Labour and Liberal parties-when at the helm of Australia's Federal
      Government-have implemented a suite of regressive policies toward individuals
      seeking asylum. This has involved enforced legal restrictions on dissenting
      voices of those working with these populations, including health professionals.
      This paper outlines Australia's contemporary offshore immigration detention
      policy and practices. It summarises evidence on asylum seeker health in detention
      centres and describes the government's practice of purposeful silencing of health
      professionals. The authors examine how Australia's treatment of asylum seekers
      violates their health rights. Based on these analyses, the authors call for
      concrete action to translate the overwhelming body of evidence on the deleterious
      impacts of immigration detention into ethical policy and pragmatic interventions.
      To this end, they provide four recommendations for action.

PMID- 29450050
TI  - The role of funders: Wellcome Trust.
AB  - Wellcome exists to improve health for everyone by helping great ideas to thrive.
      We are a global charitable foundation, both politically and financially
      independent. We support scientists and researchers take on big problems, fuel
      imaginations and spark debate. The health of the global population and the planet
      are inextricably linked but there is a poor ecological fit between what we are
      asking of the planet and its resilience. If the complex natural systems we rely
      on for clean air, fresh water, fertile soil, biodiversity and a stable climate
      are threatened, so too is our health. The challenge is to secure the health and
      well-being of present and future generations whilst responsibly stewarding the
      planet. As research continues to unravel our understanding of the vital links
      between health and the environment, we become better equipped to develop robust,
      coherent and coordinated solutions that jointly reduce threats to human health
      and to the surrounding environment that sustains it. There are already clear
      opportunities for change but more research is needed. Our Planet, Our Health was
      identified as new priority area for Wellcome in 2015. We support work that
      embraces and stimulates creative partnerships, collaborating across disciplines
      and sectors, because we believe that we need a diversity of competencies to
      tackle these complex problems. Our aim is to gain deeper insights into these
      issues, to inform the global response through transdisciplinary research and
      develop policies that will help mitigate the risks to human health.

PMID- 29450051
TI  - Migrants and health in the Nordic welfare states.
AB  - This article probes into the health of migrants with a focus on the situation in
      the Nordic universal welfare states. The Nordic welfare states are further
      compared to each other with a comparison to the EU28 if possible, including
      investigation of the differences among the four Nordic countries. This is done by
      analyzing central parameters related to access to and inequality in health care.
      The article concludes that ethnicity does not give rise by itself to differences
      in health care, including access to care, but can be seen as a marker of where
      health problems might arise due to other specific socioeconomic factors, such as
      the impact of economic inequality. Moreover, the healthy migrant paradox cannot
      be confirmed.

PMID- 29450049
TI  - Screening for frailty: older populations and older individuals.
AB  - The concept of frailty as a health dimension in old age is recent and has its
      origin in the development of geriatric medicine. Initially an unformulated
      clinical intuition, it is now defined by a diminished physiological reserve of
      multiple organs that exposes older individuals to increased vulnerability to
      stressors and a higher risk of adverse outcomes. The operational definition of
      frailty, however, is still debated. From a diversity of models, two emerged in
      the early 2000s from epidemiological studies conducted in large population-based
      aging cohorts. The body of research emphasized prospective associations between a
      frailty phenotype and a range of adverse outcomes or between a frailty index
      measuring the accumulation of deficits and death. A few studies showed promising
      spontaneous remissions in the early stages of frailty, raising expectations for
      effective interventions. Transitions between frailty stages and effective
      interventions on frailty nevertheless remain two fields needing further
      investigation. More recently, these tools have been applied as screening
      instruments in clinical settings to guide individual decision-making and orient
      treatments. New questions are raised by the use of instruments developed to
      screen frailty in epidemiological research for assessing individual situations.
      Inquiring whether frailty screening is relevant opens a Pandora's box of doubts
      and debates. There are many reasons to screen for frailty both from a public
      health and a clinical perspective that are only exacerbated by the current
      demographic evolution. Open questions remain about the feasibility of frailty
      screening, the properties of screening tools, the relevance of an integration of
      socioeconomic dimensions into screening tools, and the effectiveness of
      interventions targeting frailty. Fifteen years after the publication of the Fried
      and Rockwood landmark papers proposing operational definitions of frailty, this
      article presents an overview of current perspectives and issues around frailty
      screening in populations and in individuals.

PMID- 29450052
TI  - Refugee trauma measurement: a review of existing checklists.
AB  - Abstract: Studies have shown that a high proportion of refugees have been
      subjected to potentially traumatic experiences (PTEs). PTEs, including torture,
      are powerful predictors of mental ill health. This paper reports a review of
      refugee trauma history self-report measures used in population studies. Methods:
      A review of existing instruments and checklists, up to September 2015, was
      performed. Results: The types of measures for refugee trauma history vary from
      semi-structured interviews and medical records to extensive multi-item trauma
      checklists. The Harvard Trauma Questionnaire (HTQ) was the most commonly used
      instrument for measuring trauma history among refugee populations. Few checklists
      included PTEs during the flight. Conclusion: Trauma history checklists are often
      used as a tool to control for background variables when studying refugees' mental
      health and have mostly been developed in clinical or semi-clinical settings.
      There is a need for acceptable, reliable and valid brief checklists for measuring
      trauma in refugees, for the purpose of performing larger scale population
      studies.

PMID- 29450053
TI  - Ethnic density and mortality: aboriginal population health in Taiwan.
AB  - Background: Ethnic density (the proportion of ethnic minority populations in a
      geographic area) has emerged as an important factor determining population
      health. By examining the relationship between mortality rates and the proportion
      of aboriginal population in Taiwan, this ecological approach highlights the
      pressing need to understand why aboriginal health remains relatively
      disadvantaged affecting the population as a whole, especially given the provision
      of universal health coverage. Methods: Using combined data from various
      government departments in Taiwan, we first compare overall mortality rates
      between aboriginal people and the general population in Taiwan's 21
      administrative locations during the years 2010 and 2011. Then we describe the
      associations between ethnic density and the relative risk of 40 different causes
      of death. Results: Aboriginal people in Taiwan on average have higher overall
      mortality rates than the general population. The proportion of aboriginal
      population is associated with a higher risk of death for overall mortality,
      homicide, vehicle crashes, tuberculosis, and several alcohol-related diseases
      such as peptic ulcer, chronic liver disease, and cirrhosis. These affect the
      health of the general population in counties where aborigines are abundant.
      Conclusion: The proportion of aboriginal population may play an essential role in
      determining Taiwan's population health. When universal health coverage is in
      place, the root causes (for example, alcoholism, culture, and socioeconomic
      disadvantages) of health disparities between aboriginal populations and general
      populations need to be addressed.

PMID- 29450054
TI  - Improving the health of African Americans in the USA: an overdue opportunity for
      social justice.
AB  - Using a modified social ecological model, we conducted a review of the literature
      and nationwide statistics on African American health. We discuss the main social
      determinants of health and main health disparities, risk factors, the leading
      causes of morbidity and mortality, and access to health services for blacks in
      the USA. The mechanisms through which social determinants, including racism,
      exert their deleterious effects on black health are discussed at the macro and
      individual levels. Incarceration and mental health care issues are highlighted as
      priorities to be addressed. African Americans remain the least healthy ethnic
      group in the USA, a somber legacy of years of racial and social injustice and a
      formidable challenge to equitable health care for all. Systemic causes of
      suboptimal black health require equally systemic solutions; positive trends in
      black health indicators seem to be driven by social development programs,
      economic investment in education, participation of African Americans in policy,
      and decision-making and expansion of access to health care.

PMID- 29450056
TI  - Addressing challenges to human health in the Anthropocene epoch-an overview of
      the findings of the Rockefeller/Lancet Commission on Planetary Health.
AB  - The report of the Rockefeller Foundation/Lancet Commission on Planetary Health
      described how human health directly depends upon the environment. It takes a
      broad perspective not only acknowledging climate change as the most important
      global environmental threat to health but also recognizing other impacts,
      including dramatic loss of tropical forests, land degradation, loss of
      biodiversity, declining freshwater resources, ocean acidification, and over
      exploitation of fisheries. All pose challenges to human health gains, leading to
      the concept of planetary health-that the human condition is tied to natural
      systems. The Planetary Health Commission report highlights several major concerns
      arising from environmental change including impacts on food availability and
      quality, increases in natural disasters and population displacement, and newly
      emerging diseases, e.g. from zoonotic infections. Three challenges emerge from
      the report: the first is imagination, or conceptual challenges-better metrics are
      needed to assess human progress within the context of environmental change; the
      second is a lack of relevant knowledge, requiring more research on the inter
      linkages between environmental change and health and on the effectiveness of
      potential solutions; and the third is implementation of solutions, ensuring that
      the science is translated into policy and practice. There are many opportunities
      to promote planetary health including developing sustainable and healthy cities,
      encouraging more resilient health systems and disaster preparedness, reducing
      food waste, preserving ecosystems, and redirecting harmful subsidies in food,
      agriculture, fishery and energy sectors. Many current trends are driven by
      inequitable, inefficient, and unsustainable patterns of resource consumption and
      technological development, coupled with population growth, but solutions lie
      within reach. Prosperity must be redefined as an enhancement of the quality of
      life and the delivery of improved health for all, together with respect for
      natural systems.

PMID- 29450055
TI  - Are undocumented migrants' entitlements and barriers to healthcare a public
      health challenge for the European Union?
AB  - Undocumented migrants (UMs) are at higher risk for health problems because of
      their irregular status and the consequences of economic and social
      marginalization. Moreover, the emergent reality of undocumented migration in
      Europe calls for action in the field of management of UM's health demands as
      their access to health services has become a sensitive political and social
      issue. In this light, this paper aims to address UMs' entitlement and barriers to
      healthcare and related policies citing evidence from peer-reviewed and grey
      literature concerning people living in a country within the European Union
      without the legal right to be/remain in the destination country. A systematic
      review was performed using several databases and websites, and a total of 54
      publications in English, with full text available, were taken into consideration.
      Between 2000 and 2015, Europe hosted the second largest number of international
      migrants (20 million, 1.3 million per year) after Asia. Even though there is
      limited evidence specifically focused on UMs' health, it is possible to state
      that infectious diseases, chronic illnesses, mental disorders, maternal-child
      conditions, dental issues, acute illnesses and injuries are the most common
      pathologies. In most cases across Europe, UMs have access only to emergency care.
      Even in countries where they are fully entitled to healthcare, formal and
      informal barriers hinder them from being or feeling entitled to this right. Socio
      cultural barriers, such as language and communication problems, lack of formal
      and informal social and healthcare networks and lack of knowledge about the
      healthcare system and about informal networks of healthcare professionals are all
      common impediments. From the healthcare providers' perspective, there can be
      difficulties in providing appropriate care and in dealing with cultural and
      language barriers and false identification. Communication strategies play a
      central role in addressing the inequalities in access to healthcare services, and
      the definition and provision of specific training, focused on UMs' health needs,
      would be desirable. Improving access to healthcare for UMs is an urgent priority
      since the lack of access is proven to have serious consequences for UMs' health
      and wellbeing. Notwithstanding, few available examples of policies and best
      practices aimed at overcoming barriers in the delivery of healthcare to UMs are
      available.

PMID- 29450057
TI  - The legal and ethical aspects of the right to health of migrants in Switzerland.
AB  - The right to health of migrant populations, whether they are foreign nationals,
      foreign workers, tourists, asylum seekers or refugees, is enshrined in
      international human rights treaties. The effectiveness of the implementation of
      this fundamental right thus lies in national legal frameworks. In spite of its
      long humanitarian tradition, Switzerland has a strict migration policy, and while
      it has established a non-discriminatory legal framework for the protection and
      promotion of the right to health, its laws and regulations sometimes codify
      differences in treatment between foreign nationals and Swiss residents based on
      distinct situations. On the basis of shared responsibilities between the Federal
      State and the 26 cantons, this article describes the Swiss legal and regulatory
      approach to the right to health, the ways it is currently implemented and the
      possible vectors for an improved integration of migrants into the health system.

PMID- 29450058
TI  - NUTRItion and CLIMate (NUTRICLIM): investigating the relationship between climate
      variables and childhood malnutrition through agriculture, an exploratory study in
      Burkina Faso.
AB  - Malnutrition remains a leading cause of death in children in low- and middle
      income countries; this will be aggravated by climate change. Annually, 6.9
      million deaths of children under 5 were attributable directly or indirectly to
      malnutrition. Although these figures have recently decreased, evidence shows that
      a world with a medium climate (local warming up to 3-4  degrees C) will create an
      additional 25.2 million malnourished children. This proof of concept study
      explores the relationships between childhood malnutrition (more specifically
      stunting), regional agricultural yields, and climate variables through the use of
      remote sensing (RS) satellite imaging along with algorithms to predict the effect
      of climate variability on agricultural yields and on malnutrition of children
      under 5. The success of this proof of purpose study, NUTRItion and CLIMate
      (NUTRICLIM), should encourage researchers to apply both concept and tools to
      study of the link between weather variability, crop yield, and malnutrition on a
      larger scale. It would also allow for linking such micro-level data to climate
      models and address the challenge of projecting the additional impact of childhood
      malnutrition from climate change to various policy relevant time horizons.

PMID- 29450059
TI  - Adaptation and resilience.
AB  - Lessons learned, opportunities, and barriers to scaling up health adaptation were
      identified from evaluation reports and other materials from three multinational
      health adaptation projects covering 14 low- and middle-income countries and from
      qualitative data collected through a focus group consultation and interviews with
      key informants purposively selected for their expertise and role in health
      adaptation. The national projects aimed to increase resilience to climate
      sensitive health outcomes by focusing on incremental improvements in policies and
      programs to address climate variability and by beginning to establish enabling
      environments for further adaptation. At this early stage in implementing health
      adaptation, projects have made limited plans for scaling up specific health
      adaptation activities outside of normal ministry approaches. Scaling up is needed
      to prepare for the challenges ahead, including by improving integrated
      surveillance and other programs to manage the health risks of a changing climate.

PMID- 29450060
TI  - Why should health be a central argument in climate negotiations? Can a MOOC help
      to bring the message across?
AB  - There are four key messages from health for climate negotiations. Two positive
      ones include (i) health as a motivator for action and policy and (ii) huge health
      co-benefits to be included in the cost-benefit trade-offs of climate
      negotiations. Two warning messages: (iii) there are health-based absolute limits
      of adaptations and (iv) hotter average temperatures will cut work productivity of
      farmers and other outdoor workers as well as workers in non-air conditioned
      factories in poor countries. This paper will examine how massive open online
      courses (MOOCs) have been used in the run-up to this COP to disseminate these
      four messages to the audience of high-level policy-makers. This required a
      departure from the classic MOOC format in several ways: duration, focus on
      decision-making rationale, policy-relevant messages presented in big brush,
      leaving "traceable accounts" to evidence in two layers of resources provided:
      essential and "deep dive".

PMID- 29450061
TI  - International organizations and migrant health in Europe.
AB  - International organizations have defined and managed different aspects of migrant
      health issues for decades, yet we lack a systematic understanding of how they
      reach decisions and what they do on the ground. The present article seeks to
      clarify the state of knowledge on the relationship between international
      organizations and migrant health in Europe. To do so, we review the operations of
      six organizations widely recognized as key actors in the field of migrant health:
      the European Commission, the Regional Office for Europe of the World Health
      Organization, the International Organization on Migration, Medecins du Monde,
      Medecins Sans Frontieres, and the Open Society Foundation. We find that
      international organizations operate in a complementary fashion, with each taking
      on a unique role in migrant health provision. States often rely on international
      organizations as policy advisors or sub-contractors for interventions, especially
      in the case of emergencies. These linkages yield a complex web of relationships,
      which can vary depending on the country under consideration or the health policy
      issue in question.

PMID- 29450062
TI  - Aging and health among migrants in a European perspective.
AB  - Population aging and the associated changes in demographic structures and
      healthcare needs is a key challenge across Europe. Healthy aging strategies focus
      on ensuring the ability to maintain health, quality of life and independent
      living at old age. Concurrent to the process of population aging, the
      demographics of Europe are affected by increased migration resulting in
      substantial ethnic diversity. In this paper, we narratively review the health
      profile of the growing proportion of aging migrants in Europe, outline key
      factors shaping health among this diverse group and consider ways of addressing
      their healthcare needs. Although factors shaping aging processes are largely
      similar across populations, migrant-specific risk factors exist. These include
      exposure to health risks before and during migration; a more disadvantaged
      socioeconomic position; language barriers and low health literacy; cultural
      factors influencing health-seeking behaviours; and psychosocial vulnerability and
      discrimination affecting health and quality of life. Overall, migrants experience
      the same morbidity and mortality causes as the native populations, but with
      different relative importance, severity and age of onset and with substantial
      differences within and between migrant groups. Little is known regarding health
      behaviours among aging migrants, although differences in cancer screening
      behaviours have been identified. Indications of widening health differentials
      between migrants and native populations with age and informal barriers to quality
      healthcare for aging migrants are causes of concern. In conclusion, there is a
      need for attention to migration alongside other determinants of healthy aging.
      The diversity in individual characteristics, life course processes and contextual
      factors shaping aging processes among migrants point to the need for a sensitive
      and comprehensive approach to policies, practices and research within the field
      of healthy aging. This is important to accommodate for the needs of the growing
      number of aging migrants in Europe and counter inequities in health and well
      being at old age.

PMID- 29450063
TI  - Climate change and infectious diseases.
AB  - Global changes are major determinants for infectious diseases, although
      attributable, part of climate change remains debatable. Vector-borne diseases are
      prone to be impacted by global warming, although other factors may play a
      substantial role, evidenced by the dramatic decrease in malaria in the last
      decades in places where climate change has deep and significant effects. There is
      now evidence that in some areas of the world, e.g. Horn of Africa, warm El Nino
      Southern Oscillations (ENSO), which are observed in the South Pacific Ocean, are
      associated with higher risk of emergence of Rift Valley fever, cholera and
      malaria and during cold La Nina events, dengue fever, chikungunya and yellow
      fever. This has been observed for these and other diseases in other parts of the
      world. For example, seasonal influenza outbreaks have been more intense (i.e.
      higher number) and more severe (i.e. higher mortality) when concomitant with La
      Nina events. Since climate scientists have recently observed that climate change
      is tied to more frequent and more intense ENSO events, we may foresee increases
      in frequency and severity in emerging infectious diseases in the world.

PMID- 29450064
TI  - Sustainable, healthy cities: making the most of the urban transition.
AB  - The world is undergoing a massive urban transition, which is now both the
      greatest driver of global environmental change and the most significant influence
      on human health. Cities offer real opportunities for improving health, but
      managed poorly, they can also create or reinforce significant health deficits
      while putting severe stresses on the natural systems which support human
      civilization. Management of urban problems is rarely straightforward, as
      complexity across scales and sectors, in causal structures, actors and
      incentives, can lead to ineffective policies and unintended consequences. Systems
      thinking offers a promising way forward in its ability to deal with non-linear
      relationships and simultaneous actions and outcomes. Encompassing, on the one
      hand, analytic frameworks and methods that can provide important causal insights
      and a test bed for urban policy, and on the other, broad processes of inter- and
      trans-disciplinary engagement to better define problems and feasible solutions,
      systems approaches are critical to the current and future design and management
      of sustainable healthy cities.

PMID- 29450065
TI  - How do sustainable diets fit into the climate agenda?
AB  - Food production is a major driver of greenhouse gas (GHG) emission and other
      environmental footprints, and dietary risk factors are contributors to non
      communicable diseases. A growing body of evidence has shown that changes in what
      and how much we eat can offer benefits for both the environment and health.
      However, several data gaps and complexities remain in this research area. A
      better understanding and increased uptake of sustainable diets will require
      further research, investment, and interdisciplinary collaboration.

PMID- 29450066
TI  - Integrated mixed methods policy analysis for sustainable food systems: trends,
      challenges and future research.
AB  - Agriculture is a major contributor to greenhouse gas emissions, an important part
      of which is associated to deforestation and indirect land use change. Appropriate
      and coherent food policies can play an important role in aligning health,
      economic and environmental goals. From the point of view of policy analysis,
      however, this requires multi-sectoral, interdisciplinary approaches which can be
      highly complex. Important methodological advances in the area are not exempted
      from limitations and criticism. We argue that there is scope for further
      developments in integrated quantitative and qualitative policy analysis combining
      existing methods, including mathematical modelling and stakeholder analysis. We
      outline methodological trends in the field, briefly characterise integrated mixed
      methods policy analysis and identify contributions, challenges and opportunities
      for future research. In particular, this type of approach can help address issues
      of uncertainty and context-specific validity, incorporate multiple perspectives
      and help advance meaningful interdisciplinary collaboration in the field.
      Substantial challenges remain, however, such as the integration of key issues
      related to non-communicable disease, or the incorporation of a broader range of
      qualitative approaches that can address important cultural and ethical dimensions
      of food.

PMID- 29450067
TI  - Future Earth Health Knowledge-Action Network.
AB  - Future Earth is an international research platform providing the knowledge and
      support to accelerate our transformations to a sustainable world. Future Earth
      2025 Vision identified eight key focal challenges, and challenge #6 is to
      "Improve human health by elucidating, and finding responses to, the complex
      interactions amongst environmental change, pollution, pathogens, disease vectors,
      ecosystem services, and people's livelihoods, nutrition and well-being." Several
      studies, including the Rockefeller Foundation/Lancet Planetary Health Commission
      Report of 2015, the World Health Organization/Convention on Biological Diversity
      report and those by oneHEALTH (former ecoHEALTH), have been conducted over the
      last 30 years. Knowledge-Action Networks (KANs) are the frameworks to apply
      Future Earth principles of research to related activities that respond to
      societal challenges. Future Earth Health Knowledge-Action Network will connect
      health researchers with other natural and social scientists, health and
      environmental policy professionals and leaders in government, the private sector
      and civil society to provide research-based solutions based on better, integrated
      understanding of the complex interactions between a changing global environment
      and human health. It will build regional capacity to enhance resilience, protect
      the environment and avert serious threats to health and will also contribute to
      achieving Sustainable Development Goals. In addition to the initial partners,
      Future Earth Health Knowledge-Action Network will further nourish collaboration
      with other on-going, leading research programmes outside Future Earth, by
      encouraging them in active participation.

PMID- 29450068
TI  - Addressing planetary health challenges in Africa.
AB  - Drawing on the report of the Rockefeller Foundation-Lancet Commission on
      planetary health-Safeguarding human health in the Anthropocene epoch, this piece
      presents a discussion of the implications of the report's findings and
      conclusions for Africa. It explores the key planetary health challenges facing
      Africa and what Africa can do to address them. In addition to highlighting
      current and future trajectories of key environmental changes in Africa and their
      implications for health and well-being, this transcript from the 21st Conference
      of Parties (COP21) side event, "Healthy Lives on a Healthy Planet", identifies a
      set of priority action Africa needs to take in order to deal with these
      challenges. It ends with reflections and key recommendations from participants at
      the regional launch of the report in Nairobi, Kenya, in October 2015.

PMID- 29450070
TI  - The implications of COP21 for our future climate.
AB  - Rising CO2 in the atmosphere is the main cause of anthropogenic climate change,
      and the data shows a clear increase in global temperature of about 1  degrees C
      since pre-industrial levels. Changes in climate extremes are also occurring, with
      observed increases in the frequency of heat waves, in intense precipitation
      (rainfall and snowfall) in many places, and in sea level and storm surges. A
      changing climate with rising extremes has associated risks for food production
      and other health-related impacts. In order to limit climate change well below 2 
      degrees C, our carbon emissions must rapidly follow a decreasing trajectory to
      near zero.

PMID- 29450069
TI  - A systematic review of the use of health services by immigrants and native
      populations.
AB  - Background: Changes in migration patterns that have occurred in recent decades,
      both quantitative, with an increase in the number of immigrants, and qualitative,
      due to different causes of migration (work, family reunification, asylum seekers
      and refugees) require constant u pdating of the analysis of how immigrants access
      health services. Understanding of the existence of changes in use patterns is
      necessary to adapt health services to the new socio-demographic reality. The aim
      of this study is to describe the scientific evidence that assess the differences
      in the use of health services between immigrant and native populations. Methods:
      A systematic review of the electronic database MEDLINE (PubMed) was conducted
      with a search of studies published between June 2013 and February 2016 that
      addressed the use of health services and compared immigrants with native
      populations. MeSH terms and key words comprised Health Services Needs and
      Demands/Accessibility/Disparities/Emigrants and Immigrants/Native/Ethnic Groups.
      The electronic search was supplemented by a manual search of grey literature. The
      following information was extracted from each publication: context of the study
      (place and year), characteristics of the included population (definition of
      immigrants and their sub-groups), methodological domains (design of the study,
      source of information, statistical analysis, variables of health care use
      assessed, measures of need, socio-economic indicators) and main results. Results:
      Thirty-six publications were included, 28 from Europe and 8 from other countries.
      Twenty-four papers analysed the use of primary care, 17 the use of specialist
      services (including hospitalizations or emergency care), 18 considered several
      levels of care and 11 assessed mental health services. The characteristics of
      immigrants included country of origin, legal status, reasons for migration,
      length of stay, different generations and socio-demographic variables and need.
      In general, use of health services by the immigrants was less than or equal to
      the native population, although some differences between immigrants were also
      identified. Conclusions: This review has identified that immigrants show a
      general tendency towards a lower use of health services than native populations
      and that there are significant differences within immigrant sub-groups in terms
      of their patterns of utilization. Further studies should include information
      categorizing and evaluating the diversity within the immigrant population.

PMID- 29450071
TI  - Solving the global climate crisis: the greatest health opportunity of our times?
AB  - Today's substantial global health gains are being undermined by the threat of
      climate change. Ironically, the actions required to confront the climate crisis
      represent possibly the largest public health opportunity in more than a century.
      Health benefits from improved air quality may far outweigh the cost of clean
      energy investments. Upward trends in chronic diseases are now occurring
      throughout the world. Herein lies even more golden opportunities for public
      health through the following: first, adopting more alternative modes of
      transportation, especially those that promote "active transport" by foot or by
      bicycle, in combination with effective public transportation; and second, by
      reducing meat in the diet. In essence, there is no better time to focus on health
      as central in the climate negotiations; and in so doing, may we move faster and
      further with effective actions on climate change and the subsequent health
      benefits that will arise from a low-carbon society.

PMID- 29450073
TI  - The role of foundations: Rockefeller Foundation.
AB  - The consequences of climate change and the impacts of human activity on the
      environment have made it clearer than ever before that we must evolve our current
      model of public health to better account for the inextricable link between human
      health and the natural systems on which it depends-creating a "public health 2.0"
      that builds on the innovations of the twentieth century to account for a world
      where humans have bypassed planetary boundaries to achieve well-being. First
      coined at the Rockefeller Foundation's Centennial gathering in Beijing in 2013,
      "Planetary Health" will factor in future health and environmental harms over
      present-day gains, particularly those that disproportionately affect the poor and
      those in developing nations. To build this new field, foundations must address
      the challenge of information, increasing support for research to bridge knowledge
      gaps on the links between economic development, natural systems, and human
      health.

PMID- 29450074
TI  - Barriers and facilitators to extended working lives in Europe: a gender focus.
AB  - Background: There is a global imperative to respond to the challenge of a growing
      'old-age dependency ratio' by ensuring the workforce is healthy enough to remain
      in work for longer. Currently more than half of older workers leave before the
      default retirement age, and in some countries (e.g. the UK), the time spent in
      retirement is increasing. At the same time across Europe, there is a gender
      employment gap, with 14.5% fewer female workers between 55-64 years old, and a
      large variation in the participation of older women in the workforce (ranging
      from 30-75%). As older women are under-represented in the workforce, increasing
      employment in this group has the propensity to go some way towards reducing the
      old-age dependency ratio to ensure continued economic growth. Objectives: This
      review explores the barriers and facilitators to extended working lives in
      Europe, particularly those that impact on women. Methods: A systematic mapping
      review process was undertaken using four electronic databases, MEDLINE,
      PsychoINFO, PsychEXTRA via Ovid and AgeLine via EBSCO, using the terms, 'work',
      'ageing', 'retirement', 'pension', 'old', 'barrier', 'extended working life',
      'gender' and 'health and well-being'. Hand searching was also carried out in the
      International Journal of Aging and Human Development and the International
      Journal of Aging and Society. Results: The search resulted in 15 English language
      studies published from 1st January 2005 to the current date that met the
      inclusion criteria. Key findings: The key factors that influenced decisions to
      retire or extend working lives in Europe were health, social factors, workplace
      factors, and financial security and pension arrangements. Conclusions and
      implications of the key findings: Health was found to be the most commonly cited
      barrier to extended working lives in Europe, and a number of social inequalities
      to work exist by gender. Structural factors exist, such as the gender pay gap,
      which disadvantages women, while the nature of work itself differs by gender and
      can have a negative impact on health. Currently, women tend to exit the labour
      market earlier than men; however, changes in the state pension age are resulting
      in women being required to work for as long as men, in most countries. For women
      to remain healthy at work, workplaces need to consider a range of interventions,
      including flexible arrangements to both work and retirement to enable women to
      balance the demands of work with domestic and caring responsibilities that
      particularly impact on them.

PMID- 29450075
TI  - Positive postpartum depression screening practices and subsequent mental health
      treatment for low-income women in Western countries: a systematic literature
      review.
AB  - Problem statement and significance: Left undiagnosed and/or untreated, the short
      and long-term sequelae of postpartum depression may negatively impact both mother
      and child. In Western countries, access to mental health care is influenced by
      socioeconomic factors. The objective of this systematic literature review is to
      compile factors that hinder and improve access to postpartum depression treatment
      in low-income women after a positive screen for postpartum depression. The key
      question of focus is: what are the characteristics associated with access to
      mental health treatment for low-income women with a positive postpartum
      depression screen in Western countries? Methods: A PRISMA-based systematic
      literature review was conducted of studies published in English before February
      2016 that looked at treatment for postpartum depression in low-income women who
      had been identified with the condition. PubMed and EBSCO databases were searched
      using MESH and key terms and found 100 articles that met the selection criteria.
      After review by two independent researchers, 18 studies with 17 unique
      populations were included in the literature review. Results: Two independent
      abstractors searched the included articles for themes surrounding impediments and
      advantages for low-income women identified with postpartum depression in
      obtaining mental health treatment. Characteristics of successful mental health
      treatment included studies that employed the use of a home visitor and those that
      separated outcomes for women with previous mental health treatment. Themes that
      emerged as treatment obstacles included cultural barriers, physical barriers,
      systemic health care barriers, and social barriers. Implications for practice:
      This review will help to better inform screening and treatment priorities for
      those in the medical field who may encounter women experiencing postpartum
      depression and are not aware of the various barriers to care specific to low
      income women. This review will also help policymakers identify specific obstacles
      that are not addressed in postpartum screening mandate policies which can affect
      the implementation of these policies.

PMID- 29450072
TI  - Hispanic health in the USA: a scoping review of the literature.
AB  - Hispanics are the largest minority group in the USA. They contribute to the
      economy, cultural diversity, and health of the nation. Assessing their health
      status and health needs is key to inform health policy formulation and program
      implementation. To this end, we conducted a scoping review of the literature and
      national statistics on Hispanic health in the USA using a modified social
      ecological framework that includes social determinants of health, health
      disparities, risk factors, and health services, as they shape the leading causes
      of morbidity and mortality. These social, environmental, and biological forces
      have modified the epidemiologic profile of Hispanics in the USA, with cancer
      being the leading cause of mortality, followed by cardiovascular diseases and
      unintentional injuries. Implementation of the Affordable Care Act has resulted in
      improved access to health services for Hispanics, but challenges remain due to
      limited cultural sensitivity, health literacy, and a shortage of Hispanic health
      care providers. Acculturation barriers and underinsured or uninsured status
      remain as major obstacles to health care access. Advantageous health outcomes
      from the "Hispanic Mortality Paradox" and the "Latina Birth Outcomes Paradox"
      persist, but health gains may be offset in the future by increasing rates of
      obesity and diabetes. Recommendations focus on the adoption of the Health in All
      Policies framework, expanding access to health care, developing cultural
      sensitivity in the health care workforce, and generating and disseminating
      research findings on Hispanic health.

PMID- 29450076
TI  - An examination of the growing US undergraduate public health movement.
AB  - Objectives: With over 10,900 public health bachelor's degree graduates conferred
      in 2015, public health undergraduate education in the USA has become mainstream.
      However, with the recent establishment of a majority of the programs, the impact
      of the undergraduate programs remains largely unknown. This study examines a
      sample of undergraduate programs in public health to further elucidate the
      undergraduate landscape. Methods: Semi-structured interviews and a review of
      program websites from a sample of 39 institutions across the USA with
      undergraduate majors labeled as public health were conducted in 2015 to examine
      program content and operations. Results: Findings from the 39 programs reviewed
      demonstrated growing and diverse undergraduate public health programs rapidly
      evolving. While program enrollments, infrastructure, and curriculum varied among
      the individual programs, collectively, findings indicated increasing numbers of
      undergraduate students gaining knowledge and experience in matters related to the
      health of societies locally, nationally, and globally. Conclusions: Study
      findings suggest it is an opportune time for the field to offer guidance,
      support, and vision to these burgeoning undergraduate programs. Such engagement
      offers opportunities to advance the programs as well as increase the number of
      students attuned to societal health in whatever life roles they assume.

PMID- 29450077
TI  - Master of Public Health programmes in South Africa: issues and challenges.
AB  - Background: The demand for highly skilled public health personnel in low- and
      middle-income countries has been recognised globally. In South Africa, the need
      to train more public health professionals has been acknowledged. The Human
      Resource for Health (HRH) Strategy for South Africa includes the establishment of
      public health units at district and provincial levels. Programmes such as Master
      of Public Health (MPH) programmes are viewed as essential contributors in
      equipping health practitioners with adequate public health skills to meet the
      demands of the health care system. All MPH programmes have been instituted
      independently; there is no systematic information or comparison of programmes and
      requirements across institutions. This study aims to establish a baseline on MPH
      programmes in South Africa in terms of programme characteristics, curriculum,
      teaching workforce and graduate output. Methods: A mixed method design was
      implemented. A document analysis and cross-sectional descriptive survey,
      comprising both quantitative and qualitative data collection, by means of
      questionnaires, of all MPH programmes active in 2014 was conducted. The MPH
      programme coordinators of the 10 active programmes were invited to participate in
      the study via email. Numeric data were summarized in frequency distribution
      tables. Non-numeric data was captured, collated into one file and thematically
      analysed. Results: A total of eight MPH programmes responded to the
      questionnaire. Most programmes are affiliated to medical schools and provide a
      wide range of specialisations. The MPH programmes are run by individual
      universities and tend to have their own quality assurance, validation and
      assessment procedures with minimal external scrutiny. National core competencies
      for MPH programmes have not been determined. All programmes are battling to
      provide an appropriate supply of well-trained public health professionals as a
      result of drop-out, low throughput and delayed time to completion. Conclusion:
      The MPH programmes have consistently graduated MPH candidates, although the
      numbers differ by institution. The increasing number of enrolments coupled by
      insufficient teaching personnel and low graduate output are key challenges
      impacting on the production of public health professionals. Collaboration amongst
      the MPH programmes, standardization, quality assurance and benchmarking needs
      considerable attention.

PMID- 29450078
TI  - Polio immunization in Pakistan: ethical issues and challenges.
AB  - Background: Immunization should be considered a basic human right to health and
      well-being. It is everybody's business, and it is everybody's responsibility: the
      individual, the community, the health system and the state. This paper attempts
      to review some of the literature that highlights the ethical and religious
      concerns surrounding polio vaccination and what approaches may be used to counter
      the problems faced in Pakistan. Methods: This paper is developed through a
      literature review on public health and polio in Pakistan, consulting local,
      regional and globally published peer reviewed articles focussing on religion,
      culture, ethics and public health. Discussion: Human behaviour, including the
      utilization and acceptability of healthcare services, is greatly influenced by
      religious beliefs and dogmas. Immunization, specifically for the purpose of polio
      eradication, has been a topic under focus and in the news in Pakistan. The
      government is doing its best through a variety of interventions to increase
      access, inform the public and increase vaccination rates. Nevertheless, the
      country still faces a huge challenge from certain stern pockets of uncompromising
      populations who resist and refuse vaccination. Beliefs, practices and cultural
      norms overshadow public health priorities and ethics. Understanding of the
      context, therefore, is critical to determine the social hindrances in polio
      eradication and strategize thereon. Conclusion: Having programmatic, system-wide,
      socio-cultural and of course ethical dimensions, the policy makers and the
      programme managers in Pakistan must attempt to address the multitude of
      challenges to polio vaccination, whereby the plan of action developed within the
      ethical norms could potentially lead to an ultimate success.

PMID- 29450079
TI  - Communicating climate change and health in the media.
AB  - The translation of science from research to real-world change is a central goal
      of public health. Communication has an essential role to play in provoking a
      response to climate change. It must first raise awareness, make people feel
      involved and ultimately motivate them to take action. The goal of this research
      is to understand how the information related to this issue is being addressed and
      disseminated to different audiences-public citizens, politicians and key climate
      change stakeholders. Initial results show that the scientific voice struggles to
      globally highlight this issue to a general audience and that messages that
      address the topic do not meet the challenges, going from a dramatic framing to a
      basic adaptation framing. Communication experts can help inform scientists and
      policy makers on how to best share information about climate change in an
      engaging and motivating way. This study gives an insight about the key role of
      the media and communications in addressing themes relating to climate change and
      transmitting information to the public in order to take action.

PMID- 29450081
TI  - Human rights and the practice of medicine.
AB  - There exists a profound disconnect and misunderstanding of the utility of human
      rights in the practice of medicine that demands urgent attention. The United
      Nations Special Rapporteur, Dainius Puras, reflects on his career as a medical
      professional and why human rights in the day to day care of his patients became a
      powerful tool to strengthen his practice and ensure the dignity and well-being of
      those he served. This preface reflects on some of the troubling paradoxes
      encountered in the practice of medicine, identifying the disconnect between human
      rights and the provision of patient care as a fundamental struggle that urgently
      requires a framework for action, much like what is offered by the authors of this
      special edition. A historical reflection of the power relations between the
      medical profession and those it serves concludes with a message of hope and a
      galvanizing call for leadership from within the medical community to lead rights
      based reform in patient care.

PMID- 29450080
TI  - Residential schools and the effects on Indigenous health and well-being in Canada
      a scoping review.
AB  - Background: The history of residential schools has been identified as having long
      lasting and intergenerational effects on the physical and mental well-being of
      Indigenous populations in Canada. Our objective was to identify the extent and
      range of research on residential school attendance on specific health outcomes
      and the populations affected. Methods: A scoping review of the empirical peer
      reviewed literature was conducted, following the methodological framework of
      Arksey and O'Malley (2005). For this review, nine databases were used:
      Bibliography of Native North Americans, Canadian Health Research Collection,
      CINAHL, Google Scholar, Indigenous Studies Portal, PubMed, Scopus, Statistics
      Canada, and Web of Science. Citations that did not focus on health and
      residential school among a Canadian Indigenous population were excluded. Papers
      were coded using the following categories: Indigenous identity group, geography,
      age-sex, residential school attendance, and health status. Results: Sixty-one
      articles were selected for inclusion in the review. Most focused on the impacts
      of residential schooling among First Nations, but some included Metis and Inuit.
      Physical health outcomes linked to residential schooling included poorer general
      and self-rated health, increased rates of chronic and infectious diseases.
      Effects on mental and emotional well-being included mental distress, depression,
      addictive behaviours and substance mis-use, stress, and suicidal behaviours.
      Conclusion: The empirical literature can be seen as further documenting the
      negative health effects of residential schooling, both among former residential
      school attendees and subsequent generations. Future empirical research should
      focus on developing a clearer understanding of the aetiology of these effects,
      and particularly on identifying the characteristics that lead people and
      communities to be resilient to them.

PMID- 29450082
TI  - A human rights approach to the health implications of food and nutrition
      insecurity.
AB  - Food and nutrition insecurity continues to pose a serious global challenge,
      reflecting government shortcomings in meeting international obligations to ensure
      the availability, accessibility, and quality of food and to ensure the highest
      attainable standard of health of their peoples. With global drivers like climate
      change, urbanization, greater armed conflict, and the globalization of unhealthy
      diet, particularly in under-resourced countries, food insecurity is rapidly
      becoming an even greater challenge for those living in poverty. International
      human rights law can serve a critical role in guiding governments that are
      struggling to protect the health of their populations, particularly among the
      most susceptible groups, in responding to food and nutrition insecurity. This
      article explores and advocates for a human rights approach to food and nutrition
      security, specifically identifying legal mechanisms to "domesticate" relevant
      international human rights standards through national policy. Recognizing
      nutrition security as a determinant of public health, this article recognizes the
      important links between the four main elements of food security (i.e.,
      availability, stability, utilization, and access) and the normative attributes of
      the right to health and the right to food (i.e., availability, accessibility,
      affordability, and quality). In drawing from the evolution of international human
      rights instruments, official documents issued by international human rights
      treaty bodies, as well as past scholarship at the intersection of the right to
      health and right to food, this article interprets and articulates the
      intersectional rights-based obligations of national governments in the face of
      food and nutrition insecurity.

PMID- 29450083
TI  - Establishing undergraduate public health education: process, challenges, and
      achievements in a case study in Israel.
AB  - Background: In this paper, we describe the development process of the first
      undergraduate public health baccalaureate program, in the Ashkelon Academic
      College in Israel. Expansion of degree-granting colleges in Israel is part of the
      democratization of higher education providing access to and increasing
      educational opportunities for groups underrepresented in universities. The main
      objectives of the program at Ashkelon Academic College have been to open
      accessible and affordable career opportunities for current workers in the health
      system and for new entries to health careers for academic advancement in a
      peripheral and relatively poor region of the country. Case Presentation: The
      program focuses on well-established and literature-based learning goals of public
      health education but also includes basic medical sciences, incorporation of arts
      and sciences into public health, development of critical thinking and
      quantitative skills, experiential field learning, and integrative learning for
      facing global health challenges. The curricula of the program is composed of
      seven modules including introductory courses, methodology courses, health
      organization courses, epidemiology courses, courses related to core content of
      public health, elective courses and practicum. The first class will graduate in
      2017; this will allow for final approval of the Council of Higher Education of
      Israel and possible revision of curriculum. A second BA program is now seeking
      approval in Israel and cooperation with post-graduate schools of public health is
      developing. Conclusion s : Our program is in keeping with trends in Europe and
      the USA to broaden public health education, to reduce inequality of career
      opportunity, to expand the workforce, and to promote public health.

PMID- 29450084
TI  - March of Dimes Foundation: leading the way to birth defects prevention.
AB  - Birth defects are a major cause of mortality among children under five. In
      accordance with its mission, the March of Dimes Foundation is dedicated to
      reducing the toll of birth defects on children, families, and society. Founded in
      1938 to fight polio, March of Dimes currently focuses on prevention of birth
      defects and preterm birth and has had a major influence on surveillance,
      research, advocacy, awareness, and education related to birth defects prevention
      and care. In the USA, it has played an active role in promoting and advocating
      for newborn screening for early diagnosis and treatment of congenital disorders,
      folic acid fortification of grains for prevention of neural tube defects, and
      more recently on raising awareness about birth defects related to Zika virus
      infection. March of Dimes has played a major role in promoting prevention of
      birth defects globally by publishing data-based reports and papers related to the
      toll of birth defects and by supporting surveillance and preconception health
      education programs. March of Dimes birth defects health education materials
      directed for raising awareness among families are used worldwide. Additionally,
      March of Dimes had equipped health care workers and policy makers with essential
      information about birth defects through published materials and sponsoring of
      conferences that allow for networking and knowledge exchange. March of Dimes
      remains committed to prevention of birth defects through supporting research
      related to causes of birth defects, empowering women and girls with health
      knowledge, and advocating for policies and programs at national and global levels
      for giving every child an opportunity to attain his or her optimal level of
      health.

PMID- 29450085
TI  - Structural adjustment programmes adversely affect vulnerable populations: a
      systematic-narrative review of their effect on child and maternal health.
AB  - Structural adjustment programmes of international financial institutions have
      typically set the fiscal parameters within which health policies operate in
      developing countries. Yet, we currently lack a systematic understanding of the
      ways in which these programmes impact upon child and maternal health. The present
      article systematically reviews observational and quasi-experimental articles
      published from 2000 onward in electronic databases (PubMed/Medline, Web of
      Science, Cochrane Library and Google Scholar) and grey literature from websites
      of key organisations (IMF, World Bank and African Development Bank). Studies were
      considered eligible if they empirically assessed the aggregate effect of
      structural adjustment programmes on child or maternal health in developing
      countries. Of 1961 items yielded through database searches, reference lists and
      organisations' websites, 13 met the inclusion criteria. Our review finds that
      structural adjustment programmes have a detrimental impact on child and maternal
      health. In particular, these programmes undermine access to quality and
      affordable healthcare and adversely impact upon social determinants of health,
      such as income and food availability. The evidence suggests that a fundamental
      rethinking is required by international financial institutions if developing
      countries are to achieve the Sustainable Development Goals on child and maternal
      health.

PMID- 29450086
TI  - Human rights education in patient care.
AB  - This article explores how human rights education in the health professions can
      build knowledge, change culture, and empower advocacy. Through a study of
      educational initiatives in the field, the article analyzes different methods by
      which health professionals come to see the relevance of human rights norms for
      their work, to habituate these norms in everyday practice, and to espouse these
      norms in advocacy for social justice. The article seeks to show the
      transformative potential of education for human rights in patient care.

PMID- 29450087
TI  - Forced sterilization of women as discrimination.
AB  - There has been a long history of subjecting marginalized women to forced and
      coerced sterilization. In recent years, the practice has been documented in
      countries in North and South America, Europe, Asia, and Africa. It has targeted
      women who are ethnic and racial minorities, women with disabilities, women living
      with HIV, and poor women. A handful of courts have issued decisions on the recent
      forced sterilization of marginalized women finding that such actions violate the
      women's rights. However, they have all failed to address the women's claims of
      discrimination. The failure to acknowledge that forced sterilization is at its
      core a violation of the prohibition of discrimination undermines efforts to
      eradicate the practice. It further fails to recognize that coerced and forced
      sterilization fundamentally seeks to deny women deemed as "unworthy" the ability
      to procreate. Four key principles outlined in the human rights in patient care
      framework highlight the importance of a finding that the prohibition of
      discrimination was violated in cases of forced sterilization: the need to
      highlight the vulnerability of marginalized populations to discrimination in
      health care settings; the importance of the rights of medical providers; the role
      of the state in addressing systemic human rights violations in health care
      settings; and the application of human rights to patient care. Based on these
      principles, it is clear that finding a violation of the prohibition of
      discrimination in forced sterilization cases is critical in addressing the
      systemic nature of the practice, acknowledging the marginalization of specific
      groups and effectively ending forced sterilization through addressing the
      underlying purpose of the practice. If litigators, non-governmental organizations
      and judicial officers are mindful of these principles when dealing with cases of
      forced sterilization, it is likely that they will be better able to eradicate
      forced sterilization.

PMID- 29450089
TI  - The State's obligation to regulate and monitor private health care facilities:
      the Alyne da Silva Pimentel and the Dzebniauri cases.
AB  - The Human Rights in Patient Care framework embraces general human rights
      principles applicable to both patients and health care providers in the delivery
      of health care. Under this framework, states have a duty to ensure patient and
      provider rights in both public and private health care settings. The paper
      examines the recent decisions in Alyne Da Silva Pimentel v. Brazil of the
      Committee on the Elimination of Discrimination against Women and Dzebniauri v.
      Georgia of the European Court of Human Rights and places these decisions within
      the wider debate on the extent to which states have human rights obligations in
      private settings. Drawing on these decisions, the paper demonstrates that this
      duty can be complied with by establishing appropriate laws and regulations for
      private entities, monitoring and enforcement of the standards, and performance of
      these bodies and professionals through investigation and accountability
      procedures.

PMID- 29450088
TI  - Advancing human rights in patient care of Roma: access to health insurance in
      Macedonia.
AB  - Roma in Macedonia suffer from dire health consequences due to economic factors,
      such as high rates of unemployment and poverty, and social factors, including
      discrimination by medical providers. Although Macedonia administers a public
      health care system for its citizens, Roma frequently lack access to this system
      in contravention of the rights to health and equality enshrined in Macedonia's
      Constitution and international law. Applying a human rights in patient care
      (HRPC) framework to this problem, we discuss a facially neutral law that
      predicated access to health insurance for low-income citizens on the submission
      of a statement of income. This requirement created additional barriers to care,
      which we describe in this article. Even after the Constitutional Court declared
      the requirement invalid, the government failed to implement appropriate changes
      to the law in a timely manner. We argue this failure threatened the rule of law
      in the country and further marginalized and discriminated against Roma in
      violation of their human rights.

PMID- 29450090
TI  - Palliative care and human rights in patient care: an Armenia case study.
AB  - This paper examines palliative care within the human rights in patient care
      framework, which clarifies state obligations and addresses the rights of both
      patients and providers. In the context of palliative care, these rights extend
      beyond the right to health and include patient rights to freedom from torture,
      cruel and inhuman treatment, non-discrimination and equality, bodily integrity,
      privacy and confidentiality, information, and right to a remedy. They also
      encompass provider rights to decent working conditions, freedom of association,
      and due process. The paper then looks at a case study of Armenia, acknowledging
      how the government's commitment to palliative care, combined with awareness
      raising and advocacy by human rights organizations, created an enabling
      environment for the realization of human rights in patient care in the context of
      palliative care.

PMID- 29450091
TI  - The importance of vitamin D in maternal and child health: a global perspective.
AB  - Vitamin D and calcium are important nutrients for skeletal growth and bone
      health. Children and pregnant women are particularly vulnerable to 25-hydroxy
      vitamin D deficiency (VDD). VDD, with or without dietary calcium deficiency, can
      lead to nutritional rickets (NR), osteomalacia, and disturbances in calcium
      homeostasis. Multiple studies have linked VDD to adverse health outcomes in both
      children and pregnant women that extend beyond bone health. VDD remains an
      important global public health concern, and an important differentiation must be
      made between the impact of VDD on children and adults. Reports of increased
      incidence of NR continue to emerge. NR is an entirely preventable condition,
      which could be eradicated in infants and children worldwide with adequate vitamin
      D and calcium supplementation. The desire and necessity to put in place systems
      for preventing this potentially devastating pediatric disease should not elicit
      dispute. VDD and NR are global public health issues that require a collaborative,
      multi-level approach for the implementation of feasible preventative strategies.
      This review highlights the history, risk factors, and controversies related to
      VDD during pregnancy and childhood with a particular focus on global NR
      prevention.

PMID- 29450092
TI  - Screening for risky behaviour and mental health in young people: the YouthCHAT
      programme.
AB  - Background: The prevalence of mental health concerns and risky health behaviours
      among young people is of global concern. A large proportion of young people in
      New Zealand (NZ) are affected by depression, suicidal ideation and other mental
      health concerns, but the majority do not access help. For NZ indigenous Maori,
      the burden of morbidity and mortality associated with mental health is
      considerably higher. Targeted screening for risky behaviours and mental health
      concerns among youth in primary care settings can lead to early detection and
      intervention for emerging or current mental health and psychosocial issues.
      Opportunistic screening for youth in primary care settings is not routinely
      undertaken due to competing time demands, lack of context-specific screening
      tools and insufficient knowledge about suitable interventions. Strategies are
      required to improve screening that are acceptable and appropriate for the primary
      care environment. This article outlines the development, utilisation and ongoing
      evaluation and implementation strategies for YouthCHAT. YouthCHAT: YouthCHAT is a
      rapid, electronic, self-report screening tool that assesses risky health-related
      behaviours and mental health concerns, with a 'help question' that enables youth
      to prioritise areas they want help with. The young person can complete YouthCHAT
      in the waiting room prior to consultation, and after completion, the clinician
      can immediately access a summary report which includes algorithms for stepped
      care interventions using a strength-based approach. A project to scale up the
      implementation is about to commence, using a co-design participatory research
      approach to assess acceptability and feasibility with successive roll-out to
      clinics. In addition, a counter-balanced randomised trial of YouthCHAT versus
      clinician-administered assessment is underway at a NZ high school. Conclusion:
      Opportunistic screening for mental health concerns and other risky health
      behaviours during adolescence can yield significant health gains and prevent
      unnecessary morbidity and mortality. The systematic approaches to screening and
      provision of algorithms for stepped-care intervention will assist in delivering
      time efficient, early, more comprehensive interventions for youth with mental
      health concerns and other health compromising behaviours. The early detection of
      concerns and facilitation to evidence-based interventions has the potential to
      lead to improved health outcomes, particularly for under-served indigenous
      populations.

PMID- 29450093
TI  - Paid parental leave and family wellbeing in the sustainable development era.
AB  - Background: The Sustainable development goals (SDGs) have the potential to have a
      significant impact on maternal and child health through their commitments both to
      directly addressing health services and to improving factors that form the
      foundation of social determinants of health. To achieve change at scale, national
      laws and policies have a critical role to play in implementing the SDGs'
      commitments. One particular policy that could advance a range of SDGs and
      importantly improve maternal and infant health is paid parental leave. Methods:
      This article analyzes literature on paid leave and related policies relevant to
      SDG 1 (poverty), SDG 3 (health), SDG 5 (gender equality), SDG 8 (decent work),
      and SDG 10 (inequality). In addition, this article presents global data on the
      prevalence of policies in all 193 UN Member States. Results: A review of the
      literature finds that paid parental leave may support improvements across a range
      of SDG outcomes relevant to maternal and child health. Across national income
      levels, paid leave has been associated with lower infant mortality and higher
      rates of immunizations. In high-income countries, studies have found that paid
      leave increases exclusive breastfeeding and may improve women's economic
      outcomes. However, factors including the duration of leave, the wage replacement
      rate, and whether leave is made available to both parents importantly shape the
      impacts of paid leave policies. While most countries now offer at least some paid
      maternal leave, many provide less than the 6 months recommended for exclusive
      breastfeeding, and only around half as many provide paternal leave. Conclusions:
      To accelerate progress on the SDGs' commitments to maternal and child health, we
      should monitor countries' actions on enacting or strengthening paid leave
      policies. Further research is needed on the duration, wage replacement rate, and
      availability of leave before and after birth that would best support both child
      and parental health outcomes and social determinants of health more broadly. In
      addition, further work is needed to understand the extent to which paid leave
      policies extend to the informal economy, where the majority of women and men in
      low- and middle-income countries work.

PMID- 29450095
TI  - Strengthening health systems in Africa: a case study of the Kenya field
      epidemiology training program for local frontline health workers.
AB  - The logistical and operational challenges to improve public health practice
      capacity across Africa are well documented. This report describes Kenya's Field
      Epidemiology and Laboratory Training Program's (KFELTP) experience in
      implementing frontline public health worker training to transfer knowledge and
      practical skills that help strengthen their abilities to detect, document,
      respond to, and report unusual health events. Between May 2014 and May 2015,
      KFELTP hosted five training courses across the country to address practice gaps
      among local public health workers. Participants completed a 10-week process: two
      1-week didactic courses, a 7-week field project, and a final 1-week course to
      present and defend the findings of their field project. The first year was a
      pilot period to determine whether the program could fit into the existing 2-year
      KFELTP model and whether this frontline-level training would have an impact on
      local practice. At the end of the first year, KFELTP certified 167 frontline
      health workers in field epidemiology and data management. This paper concludes
      that local, national, and international partnerships are critical for improving
      local public health response capacity and workforce development training in an
      African setting.

PMID- 29450094
TI  - Review of infectious diseases in refugees and asylum seekers-current status and
      going forward.
AB  - An unprecedented rise in the number of asylum seekers and refugees was seen in
      Europe in 2015, and it seems that numbers are not going to be reduced
      considerably in 2016. Several studies have tried to estimate risk of infectious
      diseases associated with migration but only very rarely these studies make a
      distinction on reason for migration. In these studies, workers, students, and
      refugees who have moved to a foreign country are all taken to have the same
      disease epidemiology. A common disease epidemiology across very different migrant
      groups is unlikely, so in this review of infectious diseases in asylum seekers
      and refugees, we describe infectious disease prevalence in various types of
      migrants. We identified 51 studies eligible for inclusion. The highest infectious
      disease prevalence in refugee and asylum seeker populations have been reported
      for latent tuberculosis (9-45%), active tuberculosis (up to 11%), and hepatitis B
      (up to 12%). The same population had low prevalence of malaria (7%) and hepatitis
      C (up to 5%). There have been recent case reports from European countries of
      cutaneous diphtheria, louse-born relapsing fever, and shigella in the asylum
      seeking and refugee population. The increased risk that refugees and asylum
      seekers have for infection with specific diseases can largely be attributed to
      poor living conditions during and after migration. Even though we see high
      transmission in the refugee populations, there is very little risk of spread to
      the autochthonous population. These findings support the efforts towards creating
      a common European standard for the health reception and reporting of asylum
      seekers and refugees.

PMID- 29450096
TI  - Post-graduate medical education in public health: the case of Italy and a call
      for action.
AB  - Public health technical expertise is of crucial importance to inform decision
      makers' action in the field of health and its broader determinants. Improving
      education and training of public health professionals for both practice and
      research is the starting point to strengthen the role of public health so that
      current health challenges can be efficiently tackled. At the Association of
      Schools of Public Health in the European Region (ASPHER) Deans' & Directors' 2017
      Annual Retreat, we presented the structure and management of public health
      training system in Italy, and we reported recent data on Italian public health
      specialists' educational experience, employment opportunities and job
      satisfaction. Public health training in Italy is implemented in the context of
      the post-graduate medical education residency programme in Hygiene and Preventive
      Medicine, delivered by 34 University-based Schools of Public Health. We report
      relatively high employment rates across the county and wide spectrum of career
      opportunities for young public health specialists. However, job security is low
      and training expectations only partially met. We call upon other Schools of
      Public Health to scale up the survey within the broad ASPHER community in a
      shared and coordinated action of systematically collecting useful data that can
      inform the development of public health education and training models, their
      implementation and fruitful interaction with population health, health systems
      and services.

PMID- 29450097
TI  - Documenting legal status: a systematic review of measurement of undocumented
      status in health research.
AB  - Background: Undocumented status is rarely measured in health research, yet it
      influences the lives and well-being of immigrants. The growing body of research
      on undocumented status and health shows the need to assess the measurement of
      this legal status. We discuss the definition of undocumented status, conduct a
      systematic review of the methodological approaches currently taken to measure
      undocumented status of immigrants in the USA, and discuss recommendations for
      advancement of measurement methods. Methods: We conducted a systematic review of
      61 studies indexed in PubMed, conducted in the USA, and published from 2004 to
      2014. We categorized each of the studies' data source and type, measurement type,
      and information for classifying undocumented participants. Studies used self
      reported or proxy measures of legal status. Results: Information to classify
      undocumented participants included self-reported status, possession of a Social
      Security number, possession of health insurance or institutional resources,
      concern about deportation, and participant characteristics. Findings show it is
      feasible to collect self-reported measures of undocumented status. Conclusions:
      We recommend that researchers collect self-reported measures of undocumented
      status whenever possible and limit the use of proxy measures. Validated and
      standardized measures are needed for within and across country measurement.
      Authors should provide methodological information about measurement in
      publications. Finally, individuals who are undocumented should be included in the
      development of these methodologies. Trial registration: This systematic review is
      not registered.

PMID- 29450098
TI  - International financial institutions and human rights: implications for public
      health.
AB  - Serving as lender of last resort to countries experiencing unsustainable levels
      of public debt, international financial institutions have attracted intense
      controversy over the past decades, exemplified most recently by the popular
      discontent expressed in Eurozone countries following several rounds of austerity
      measures. In exchange for access to financial assistance, borrowing countries
      must settle on a list of often painful policy reforms that are aimed at balancing
      the budget. This practice has afforded international financial institutions
      substantial policy influence on governments throughout the world and in a wide
      array of policy areas of direct bearing on human rights. This article reviews the
      consequences of policy reforms mandated by international financial institutions
      on the enjoyment of human rights, focusing on the International Monetary Fund and
      World Bank. It finds that these reforms undermine the enjoyment of health rights,
      labour rights, and civil and political rights, all of which have deleterious
      implications for public health. The evidence suggests that for human rights
      commitments to be met, a fundamental reorientation of international financial
      institutions' activities will be necessary.

PMID- 29450100
TI  - Human rights in patient care and public health-a common ground.
AB  - Medical law and public health law have both served extensively as instruments of
      health protection and promotion-yet both are limited in their effect and scope
      and do not sufficiently cover nor supply a remedy to systematic, rather than
      anecdotal, mistreatments in the health care system. A possible solution to this
      deficiency may be found in the human rights in patient care legal approach. The
      concept of human rights in patient care is a reframing of international human
      rights law, as well as constitutional thought and tools, into a coherent approach
      aimed at the protection and furthering of both personal and communal health. It
      applies human rights discourse and human rights law onto the patient care setting
      while moving away from the narrow consumeristic view of health care delivery. By
      applying human rights in patient care approach, both national and international
      courts may and should serve as policy influencing instruments, protecting the
      rights of the most vulnerable and prejudiced against groups, which are want of a
      remedy through traditional patients' rights legal schemes.

PMID- 29450099
TI  - The impact of programs for prevention of mother-to-child transmission of HIV on
      health care services and systems in sub-Saharan Africa - A review.
AB  - Background: The global scale-up of Prevention of mother-to-child transmission
      (PMTCT) services is credited for a 52% worldwide decline in new HIV infections
      among children between 2001 and 2012. However, the epidemic continues to
      challenge maternal and paediatric HIV control efforts in Sub Saharan Africa
      (SSA), with repercussions on other health services beyond those directly
      addressing HIV and AIDS. This systematised narrative review describes the effects
      of PMTCT programs on other health care services and the implications for
      improving health systems in SSA as reported in the existing articles and
      scientific literature. The following objectives framed our review:To describe the
      effects of PMTCT on health care services and systems in SSA and assess whether
      the PMTCT has strengthened or weakened health systems in SSATo describe the
      integration of PMTCT and its extent within broader programs and health systems.
      Methods: Articles published in English and French over the period 1st January
      2007 (the year of publication of WHO/UNICEF guidelines on global scale-up of the
      PMTCT) to 31 November 2016 on PMTCT programs in SSA were sought through searches
      of electronic databases (Medline and Google Scholar). Articles describing the
      impact (positive and negative effects) of PMTCT on other health care services and
      those describing its integration in health systems in SSA were eligible for
      inclusion. We assessed 6223 potential papers, reviewed 225, and included 57.
      Results: The majority of selected articles offered arguments for increased health
      services utilisation, notably of ante-natal care, and some evidence of beneficial
      synergies between PMTCT programs and other health services especially maternal
      health care, STI prevention and early childhood immunisation. Positive and
      negative impact of PMTCT on other health care services and health systems are
      suggested in thirty-two studies while twenty-five papers recommend more
      integration and synergies. However, the empirical evidence of impact of PMTCT
      integration on broader health systems is scarce. Underlying health system
      challenges such as weak physical and human resource infrastructure and poor
      working conditions, as well as social and economic barriers to accessing health
      services, affect both PMTCT and the health services with which PMTCT interacts.
      Conclusions: PMTCT services increase to some extent the availability,
      accessibility and utilisation of antenatal care and services beyond HIV care.
      Vertical PMTCT programs work, when well-funded and well-managed, despite poorly
      functioning health systems. The beneficial synergies between PMTCT and other
      services are widely suggested, but there is a lack of large-scale evidence of
      this.

PMID- 29450101
TI  - Implementing SBIRT (Screening, Brief Intervention and Referral to Treatment) in
      primary care: lessons learned from a multi-practice evaluation portfolio.
AB  - Background: Screening, Brief Intervention and Referral to Treatment (SBIRT) is a
      public health framework approach used to identify and deliver services to those
      at risk for substance-use disorders, depression, and other mental health
      conditions. Primary care is the first entry to the healthcare system for many
      patients, and SBIRT offers potential to identify these patients early and assist
      in their treatment. There is a need for pragmatic "best practices" for
      implementing SBIRT in primary care offices geared toward frontline providers and
      office staff. Methods: Ten primary care practices were awarded small community
      grants to implement an SBIRT program in their location. Each practice chose the
      conditions for which they would screen, the screening tools, and how they would
      provide brief intervention and referral to treatment within their setting. An
      evaluation team communicated with each practice throughout the process,
      collecting quantitative and qualitative data regarding facilitators and barriers
      to SBIRT success. Using the editing method, the qualitative data were analyzed
      and key strategies for success are detailed for implementing SBIRT in primary
      care. Results: The SBIRT program practices included primary care offices,
      federally qualified health centers, school-based health centers, and a safety-net
      emergency department. Conditions screened for included alcohol abuse, drug abuse,
      depression, anxiety, child safety, and tobacco use. Across practices, 49,964
      patients were eligible for screening and 36,394 pre-screens and 21,635 full
      screens were completed. From the qualitative data, eight best practices for
      primary care SBIRT are described: Have a practice champion; Utilize an
      interprofessional team; Define and communicate the details of each SBIRT step;
      Develop relationships with referral partners; Institute ongoing SBIRT training;
      Align SBIRT with the primary care office flow; Consider using a pre-screening
      instrument, when available; and Integrate SBIRT into the electronic health
      record. Conclusions and implications: SBIRT is an effective tool that can empower
      primary care providers to identify and treat patients with substance use and
      mental health problems before costly symptoms emerge. Using the pragmatic best
      practices we describe, primary care providers may improve their ability to
      successfully create, implement, and sustain SBIRT in their practices.

PMID- 29450102
TI  - What is known about sexual and reproductive health in Latin American and
      Caribbean mining contexts? A systematic scoping review.
AB  - Background: Latin America and the Caribbean (LAC) has experienced an
      unprecedented mining boom since the mid-2000s with unknown effects on sexual and
      reproductive health (SRH). This study takes the essential first steps of
      summarizing the available literature regarding SRH in mining contexts in LAC,
      identifying critical gaps in knowledge, and discussing main implications for
      future research. Methods: We conducted a scoping review with a systematic search
      of health literature in four databases, reference lists of selected papers, and
      citations in Google Scholar. Results: The systematic search yielded 592 primary
      references and 16 articles from LAC. The 11 papers finally selected were
      conducted in gold-mining contexts in Brazil, Venezuela, Guyana, Peru, and
      Colombia, between 1995 and 2016. Ten studies centered on measuring HIV/STD
      prevalence among mineworkers and other populations; few examined associated risk
      factors. Eight studies reported high HIV/STD prevalence in the study population.
      None of the studies explored broader SRH issues. Conclusions: Available research
      is scarce and provides limited evidence on SRH in LAC mining contexts. Critical
      gaps include little knowledge on (1) broader SRH impacts besides HIV/STDs, (2)
      SRH in settings different from gold-mining contexts in Amazon countries, (3)
      mechanisms shaping SRH in LAC mining contexts, and (4) effective interventions in
      these scenarios. Future research must consider the distinctive demographic,
      environmental, socioeconomic, and gender dynamics triggered by the mining economy
      in the analysis of the relationship between mining and SRH, particularly in a
      period of extractive boom.

PMID- 29450103
TI  - Public health failure in the prevention of neural tube defects: time to abandon
      the tolerable upper intake level of folate.
AB  - The neural tube defects anencephaly and spina bifida are two of the most common
      serious congenital malformations. Most cases can be prevented by consuming
      sufficient folic acid immediately before pregnancy and in early pregnancy.
      Fortification of flour with folic acid to prevent these defects has been
      implemented in 81 countries without public objection or indication of harm. An
      obstacle to the wider adoption of fortification arises from the creation of a
      "tolerable upper intake level" for folate (which includes natural food folate as
      well as synthetic folic acid), and which has been set at 1 mg/day, thereby
      proscribing higher folate intakes. Increasing the intake of folic acid in a
      population will necessarily increase the number of people with a folate intake
      greater than 1 mg per day, and this concern is obstructing folic acid
      fortification. This paper shows that the scientific basis for setting any upper
      limit, let alone one at 1 mg/day, is flawed. An upper intake level is therefore
      unnecessary and should be removed, thus allaying unjustified concerns about folic
      acid fortification. As a result, the full global opportunity to prevent two
      serious fatal or disabling disorders can and should be realized.

PMID- 29450104
TI  - Strengthening effective preventive services for refugee populations: toward
      communities of solution.
AB  - Refugee populations have unequal access to primary care and may not receive
      appropriate health screening or preventive service recommendations. They
      encounter numerous health care disadvantages as a consequence of low-income
      status, race and ethnicity, lower educational achievement, varying degrees of
      health literacy, and limited English proficiency. Refugees may not initially
      embrace the concept of preventive care, as these services may have been
      unavailable in their countries of origin, or may not be congruent with their
      beliefs on health care. Effective interventions in primary care include the
      appropriate use of culturally and linguistically trained interpreters for health
      care visits and use of evidence-based guidelines. Effective approaches for the
      delivery of preventive health and wellness services require community engagement
      and collaborations between public health and primary care. In order to provide
      optimal preventive and longitudinal screening services for refugees, policies and
      practice should be guided by unimpeded access to robust primary care systems.
      These systems should implement evidence-based guidelines, comprehensive health
      coverage, and evaluation of process and preventive care outcomes.

PMID- 29450105
TI  - Infection Versus Hematoma Following Surgical Treatment of Proximal Femoral
      Fractures in Geriatric Patients.
AB  - Introduction: The surgical treatment of proximal femoral fractures predominantly
      involves geriatric patients and is associated with high morbidity and mortality.
      However, analyses on postoperative infections or hematoma are rare. Methods:
      Patients requiring surgical revision due to infection (n = 90) or hematoma (n =
      77) in the postoperative phase were identified from an electronic database of
      2000 consecutive patients surgically treated for proximal femoral fractures
      between 2006 and 2014. Demographic and clinical data were retrieved, including
      information on the pathogens in patients with infection. A follow-up on morbidity
      and mortality was conducted via telephone for at least 2 years postsurgery.
      Results: The follow-up rate was 100%, and the mean age was 81.9 years. The
      incidence rate of infection was 4.1% (90/2000), and women were commonly affected.
      Staphylococcus aureus and Staphylococcus epidermidis were the most commonly
      detected pathogens (35.5% and 25.5%, respectively). Mixed infections were
      observed in 15 patients, and Methicillin-resistant Staphylococcus aureus
      infections were observed in only 4 patients. A total of 77 (85.6%) infections
      occurred within 30 days postsurgery. The implant was preserved in 76 (84.4%)
      patients, and resection arthroplasty was required in 14 patients. Dementia and
      pertrochanteric fractures were significantly more common in the infection than in
      the hematoma group. Although infections were associated with high mortality rates
      for up to 2 years postsurgery, the rates did not significantly differ from those
      in the hematoma control group. Conclusion: One of every 2 patients who developed
      an infection following the surgical treatment of a proximal femoral fracture died
      within 2 years postsurgery. In addition, infections were significantly associated
      with dementia. Avoiding postoperative infection should be a high priority in the
      surgical treatment of proximal femoral fractures.

PMID- 29450106
TI  - Optical System Design for Noncontact, Normal Incidence, THz Imaging of in vivo
      Human Cornea.
AB  - Reflection mode Terahertz (THz) imaging of corneal tissue water content (CTWC) is
      a proposed method for early, accurate detection and study of corneal diseases.
      Despite promising results from ex vivo and in vivo cornea studies, interpretation
      of the reflectivity data is confounded by the contact between corneal tissue and
      dielectric windows used to flatten the imaging field. Herein, we present an
      optical design for non-contact THz imaging of cornea. A beam scanning methodology
      performs angular, normal incidence sweeps of a focused beam over the corneal
      surface while keeping the source, detector, and patient stationary. A
      quasioptical analysis method is developed to analyze the theoretical resolution
      and imaging field intensity profile. These results are compared to the electric
      field distribution computed with a physical optics analysis code. Imaging
      experiments validate the optical theories behind the design and suggest that
      quasioptical methods are sufficient for designing of THz corneal imaging systems.
      Successful imaging operations support the feasibility of non-contact in vivo
      imaging. We believe that this optical system design will enable the first,
      clinically relevant, in vivo exploration of CTWC using THz technology.

PMID- 29450107
TI  - Macrogenomic engineering via modulation of the scaling of chromatin packing
      density.
AB  - Many human diseases result from the dysregulation of the complex interactions
      between tens to thousands of genes. However, approaches for the transcriptional
      modulation of many genes simultaneously in a predictive manner are lacking. Here,
      through the combination of simulations, systems modelling and in vitro
      experiments, we provide a physical regulatory framework based on chromatin
      packing-density heterogeneity for modulating the genomic information space.
      Because transcriptional interactions are essentially chemical reactions, they
      depend largely on the local physical nanoenvironment. We show that the regulation
      of the chromatin nanoenvironment allows for the predictable modulation of global
      patterns in gene expression. In particular, we show that the rational modulation
      of chromatin density fluctuations can lead to a decrease in global
      transcriptional activity and intercellular transcriptional heterogeneity in
      cancer cells during chemotherapeutic responses to achieve near-complete cancer
      cell killing in vitro. Our findings represent a 'macrogenomic engineering'
      approach to modulating the physical structure of chromatin for whole-scale
      transcriptional modulation.

PMID- 29450108
TI  - Decorin-containing collagen hydrogels as dimensionally stable scaffolds to study
      the effects of compressive mechanical loading on angiogenesis.
AB  - Angiogenesis is a critical component during wound healing, and the process is
      sensitive to mechanical stimuli. Current in vitro culture environments used to
      investigate three-dimensional microvascular growth often lack dimensional
      stability and the ability to withstand compression. We investigated the ability
      of decorin, a proteoglycan known to modulate collagen fibrillogenesis,
      incorporated into a collagen hydrogel to increase construct dimensional stability
      while maintaining vascular growth. Decorin did not affect microvascular growth
      parameters, while increasing the compressive modulus of collagen gels and
      significantly reducing the contraction of 3% collagen gels after 16 days in
      culture.

PMID- 29450109
TI  - Determination of diffusion coefficients in live cells using fluorescence recovery
      after photobleaching with wide-field fluorescence microscopy.
AB  - Fluorescence recovery after photobleaching (FRAP) enables characterization of
      quantitative dynamic properties such as diffusion coefficients of fluorescent
      molecules in living cells by analyzing the recovery of fluorescence intensity
      after photobleaching in a specific cellular compartment or area. To
      quantitatively determine high intracellular diffusion coefficients, a suitable
      optical system as well as an appropriate model for fast diffusion analysis is
      necessary. Here, we propose a procedure to quantify the diffusion coefficient of
      rapidly-diffusing fluorescent molecules that makes use of an epi-fluorescence
      microscope with a photobleaching laser in combination with established models for
      diffusion analysis. Analysis for the diffusion coefficients of tandemly
      oligomerized green flurescent proteins (GFPs) in living cells when changing the
      photobleaching times showed that photobleaching with shorter times than the
      diffusion speed indicated not the only way to obtain appropriate diffusion
      coefficients of fast-moving molecules. Our results also showed that the apparent
      spreading of the effective radius of the photobleached area works as a correction
      factor for determining appropriate diffusion coefficients of fast-moving
      molecules like monomeric GFPs. Our procedure provides a useful approach for
      quantitative measurement of diffusion coefficients in living cells. This
      procedure is relevant for characterizing dynamic molecular interactions,
      especially of fast-moving molecules, and is relevant for studies in many
      biological fields.

PMID- 29450110
TI  - Quantitative analyses of the equilibria among DNA complexes of a blue-light
      regulated bZIP module, Photozipper.
AB  - Aureochrome1 is a blue-light-receptor protein identified in a stramenopile alga,
      Vaucheria frigida. Photozipper (PZ) is an N-terminally truncated, monomeric, V.
      frigida aureochrome1 fragment containing a basic leucine zipper (bZIP) domain and
      a light-oxygen-voltage (LOV)-sensing domain. PZ dimerizes upon photoexcitation
      and consequently increases its affinity for the target sequence. In the present
      study, to understand the equilibria among DNA complexes of PZ, DNA binding by PZ
      and mutational variants was quantitatively investigated by electrophoretic
      mobility-shift assay and fluorescence-correlation spectroscopy in the dark and
      light states. DNA binding by PZ was sequence-specific and light-dependent. The
      half-maximal effective concentration of PZ for binding to the target DNA sequence
      was ~40 nM in the light, which was >10-fold less than the value in the dark. By
      contrast, the dimeric PZ-S2C variant (with intermolecular disulfide bonds) had
      higher affinity for the target sequence, with dissociation constants of ~4 nM,
      irrespective of the light conditions. Substitutions of Glu159 and Lys164 in the
      leucine zipper region decreased the affinity of PZ for the target sequence,
      especially in the light, suggesting that these residues form inter-helical salt
      bridges between leucine zipper regions, stabilizing the dimer-DNA complex. Our
      quantitative analyses of the equilibria in PZ-DNA-complex formation suggest that
      the blue-light-induced dimerization of LOV domains and coiled-coil formation by
      leucine zipper regions are the primary determinants of the affinity of PZ for the
      target sequence.

PMID- 29450111
TI  - The binding structure and affinity of photodamaged duplex DNA with members of the
      photolyase/cryptochrome family: A computational study.
AB  - Photolyases (PHRs) and cryptochromes (CRYs) belong to the same family known as
      blue-light photoreceptors. Although their amino acid sequences and corresponding
      structures are similar to each other, they exert different functions. PHRs
      function as an enzyme to repair UV-induced deoxyribonucleic acid (DNA) lesions
      such as a cyclobutane pyrimidine dimer (CPD) and a (6-4) photoproduct ((6-4)pp),
      whereas CRYs are a circadian photoreceptor in plants and animals and at the same
      time they control the photoperiodic induction of flowering in plants. When a new
      type cryptochrome was identified, it was assumed that another type of CRYs,
      cryptochrome-DASH (CRY-DASH), which is categorized as a subfamily of
      photolyase/cryptochrome family, would possess the DNA photolyase activity.
      However, CRY-DASH had a weak DNA photolyase activity, but the reason for this is
      still unclear. To clarify the reason, we performed molecular dynamics (MD)
      simulations for a complex of CPD-PHR or CRY-DASH with damaged double-stranded DNA
      (dsDNA) and estimated the binding free energy, DeltaGbind, between the protein
      and the damaged dsDNA by using a molecular mechanics/Poisson-Boltzmann surface
      area (MM/PBSA) method. DeltaGbind for both proteins were -35 and 57 kcal mol-1,
      respectively, indicating that the structural stability of CRY-DASH was lower than
      that of CPD-PHR upon the damaged dsDNA binding. In particular, the number of
      amino acid residues relevant to the damaged dsDNA binding on the CRY-DASH surface
      was smaller than that on CPD-PHR. Therefore, the present result suggests that CRY
      DASH has a weak DNA photolyase activity because it has a lower binding affinity
      than CPD-PHR.

PMID- 29450112
TI  - Effect of Bacillus pumilus CCIBP-C5 on Musa-Pseudocercospora fijiensis
      interaction.
AB  - The effect of antifungal activity of culture filtrate (CF) of Bacillus pumilus
      strain CCIBP-C5, an isolate from a phyllosphere of banana (Musa) leaves, was
      determined on Pseudocercospora fijiensis challenged banana plants. The CF was
      shown to decrease the fungal biomass and induce changes in banana plant. In this
      sense, at 70 days post inoculation (dpi), a lower infection index as well as a
      decrease in fungal biomass after 6 dpi was obtained in treated plants with
      respect to control ones. At the same time, changes in the activities of several
      enzymes related to plant defense responses, such as phenylalanine ammonia lyase,
      chitinases, beta-1,3-glucanases and peroxidases were observed. These results
      indicate that B. pumilus CCIBP-C5 has a potential role for biological control of
      P. fijiensis possibly due to the production of antifungal metabolites.

PMID- 29450113
TI  - Potential improvement of biogas production from fallen teak leaves with co
      digestion of microalgae.
AB  - Biogas production from anaerobic co-digestion of fallen teak leaves (Tectona
      grandis) and microalgae (Chlorella vulgaris) were investigated. In this study,
      teak leaves and algae mixtures with or without pretreatment were used as the
      substrates and digested in 1-L of anaerobic fermenter, then optimal conditions
      were performed in 6-L fermenter. Pretreatment was performed using sodium
      hydroxide (NaOH) solution (w/v) at different conditions (0, 2, 3 and 4%), with
      different total solid (TS) ratios (10, 15 and 20%). The digesters were placed in
      an incubator at 34-36  degrees C for 45 days. The results showed that the co
      digestion of pretreated (10% TS with 2% NaOH) of teak leaves and algae was
      significantly higher in terms of biodegradability of TS, VS, COD along with
      biogas yield, methane potential and highest yield was achieved 71.90% than those
      obtained by mono-digestion. Thus, results demonstrated that anaerobic
      fermentation of teak leaves and microalgae in digester system could get as high
      methane yield.

PMID- 29450114
TI  - Flavonoid-rich extract of Chromolaena odorata modulate circulating GLP-1 in
      Wistar rats: computational evaluation of TGR5 involvement.
AB  - : Chromolaena odorata is a major bio-resource in folkloric treatment of diabetes.
      In the present study, its anti-diabetic component and underlying mechanism were
      investigated. A library containing 140 phytocompounds previously characterized
      from C. odorata was generated and docked (Autodock Vina) into homology models of
      dipeptidyl peptidase (DPP)-4, Takeda-G-protein-receptor-5 (TGR5), glucagon-like
      peptide 1 (GLP1) receptor, renal sodium dependent glucose transporter (SGLUT)-1/2
      and nucleotide-binding oligomerization domain (NOD) proteins 1&2. GLP-1 gene (RT
      PCR) modulation and its release (EIA) by C. odorata were confirmed in vivo. From
      the docking result above, TGR5 was identified as a major target for two key C.
      odorata flavonoids (5,7-dihydroxy-6-4-dimethoxyflavanone and homoesperetin-7
      rutinoside); sodium taurocholate and C. odorata powder included into the diet of
      the animals both raised the intestinal GLP-1 expression versus control (p <
      0.05); When treated with flavonoid-rich extract of C. odorata (CoF) or malvidin,
      circulating GLP-1 increased by 130.7% in malvidin-treated subjects (0 vs. 45
      min). CoF treatment also resulted in 128.5 and 275% increase for 10 and 30 mg/kg
      b.w., respectively. CONCLUSIONS: The results of this study support that C.
      odorata flavonoids may modulate the expression of GLP-1 and its release via TGR5.
      This finding may underscore its anti-diabetic potency.

PMID- 29450115
TI  - Plipastatin A1 produced by a marine sediment-derived Bacillus amyloliquefaciens
      SH-B74 contributes to the control of gray mold disease in tomato.
AB  - Certain Bacillus species have the capacity to produce cyclic lipopeptides and
      these lipopeptides are promising determinants contributing to the biocontrol of
      plant diseases. In the current study, a cyclic lipopeptide plipastatin A1 was
      isolated from the fermentation broth of a marine sediment-derived Bacillus
      amyloliquefaciens SH-B74 by the combination of solid-phase extraction and
      reversed-phase high-performance liquid chromatography, and its structure was
      identified by tandem mass spectrometry, high-resolution electro-spray ionization
      mass spectrometry, and gas chromatography-mass spectrometry together with nuclear
      magnetic resonance analysis. Moreover, data from activity evaluation revealed
      that plipastatin A1 has excellent in vitro activity on the suppression of the
      conidia germination of B. cinerea, the causal agent of gray mold disease in
      tomato. Furthermore, plipastatin A1 can successfully decrease the incidence of
      gray mold disease on tomato leaves at 50 uM concentration. This study indicates
      that B. amyloliquefaciens SH-B74 appears to be a potentially sustainable
      pesticide to control gray mold disease in tomato plants, and its cyclic
      lipopeptide plipastatin A1 plays an important role in the in vitro and in planta
      biocontrol of B. cinerea.

PMID- 29450116
TI  - The potential of the newly isolated thermotolerant Kluyveromyces marxianus for
      high-temperature ethanol production using sweet sorghum juice.
AB  - In this work, the newly isolated thermotolerant Kluyveromyces marxianus DBKKUY
      103 exhibited a high ethanol fermentation efficiency at high temperatures using
      sweet sorghum juice (SSJ). The highest ethanol concentrations and productivities
      achieved under the optimum conditions using thermotolerant K. marxianus DBKKUY
      103 were 85.16 g/l and 1.42 g/l.h at 37  degrees C and 83.46 g/l and 1.39 g/l.h
      at 40  degrees C, respectively. The expression levels of genes during ethanol
      fermentation at 40  degrees C were evaluated and the results found that the
      transcriptional levels of the RAD10, RAD14, RAD33, RAD50, ATPH, ATP4, ATP16, and
      ATP20 genes were up-regulated compared with those at 30  degrees C, suggesting
      that the high growth and high ethanol production efficiencies of K. marxianus
      DBKKUY-103 during high-temperature ethanol production associated with the genes
      involved in DNA repair and ATP production.

PMID- 29450117
TI  - Comparison of response surface methodology and artificial neural network to
      enhance the release of reducing sugars from non-edible seed cake by autoclave
      assisted HCl hydrolysis.
AB  - In the current investigation, statistical approaches were adopted to hydrolyse
      non-edible seed cake (NESC) of Pongamia and optimize the hydrolysis process by
      response surface methodology (RSM). Through the RSM approach, the optimized
      conditions were found to be 1.17%v/v of HCl concentration at 54.12 min for
      hydrolysis. Under optimized conditions, the release of reducing sugars was found
      to be 53.03 g/L. The RSM data were used to train the artificial neural network
      (ANN) and the predictive ability of both models was compared by calculating
      various statistical parameters. A three-layered ANN model consisting of 2:12:1
      topology was developed; the response of the ANN model indicates that it is
      precise when compared with the RSM model. The fit of the models was expressed
      with the regression coefficient R2, which was found to be 0.975 and 0.888,
      respectively, for the ANN and RSM models. This further demonstrated that the
      performance of ANN was better than that of RSM.

PMID- 29450118
TI  - Elite hairy roots of Raphanus sativus (L.) as a source of antioxidants and
      flavonoids.
AB  - An efficient protocol for hairy root induction in radish was established by
      optimizing several parameters that affect the efficiency of Agrobacterium
      rhizogenes-mediated transformations. Explants wounded using sterile hypodermic
      needle, infected with Agrobacterium suspension (0.6 OD600) for 10 min and co
      cultivated in 1/2 MS medium containing acetosyringone (100 uM) for 2 days
      displayed maximum percentage of hairy root induction using MTCC 2364 (77.6%) and
      MTCC 532 (67.6%). On further experiments with MTCC 2364 initiated hairy roots,
      maximum biomass accumulation (fresh weight = 9.50 g; dry weight = 1.48 g) was
      achieved in liquid 1/2 MS medium supplemented with 87.6 mM sucrose after 40 days
      of culture. Transgenic state of hairy roots of MTCC 2364 was confirmed by
      polymerase chain reaction using rolB- and rolC-specific primers. The MTCC 2364
      induced hairy roots produced higher amount of phenolic (33.0 mg g-1), flavonoid
      (48.0 mg g-1), and quercetin (114.8 mg g-1) content compared to auxin-induced
      roots of non-transformed radish. Furthermore, the results of ferric reducing
      antioxidant power and 1,1-diphenyl-2-picrylhydrazyl assay confirmed that the
      antioxidant activity of MTCC 2364 root extracts was improved when compared to
      auxin-induced roots of non-transformed radish. The present study offers a new
      insight in radish for production of phenolics and flavonoids (quercetin) using A.
      rhizogenes-mediated hairy root induction.

PMID- 29450119
TI  - Evidence of antidiabetic activity of Spirulina fusiformis against streptozotocin
      induced diabetic Wistar albino rats.
AB  - The aim of our study is to investigate the protective effect of Spirulina
      fusiformis against streptozotocin-induced diabetes in Wistar albino rats. Rats
      were divided into five groups: group I was normal control, group II was diabetic
      control (50 mg/kg b.w. of streptozotocin, i.p.), group III was Spirulina
      fusiformis (400 mg/kg b.w., p.o.) treated diabetic rats; group IV was
      Glibenclamide (0. 6 mg/kg b.w., p.o.) treated diabetic rats and group V was
      treated with Spirulina fusiformis (400 mg/kg b.w., p.o.) alone. There was
      significant elevation in the levels of blood glucose, serum lipid profile and
      serum renal markers (total protein, urea, creatinine and uric acid) in the
      diabetic rats. Also, diabetic rats showed significantly (P < 0.05) reduced
      antioxidant status (reduced levels of superoxide dismutase, catalase, glutathione
      peroxidase, glutathione-S-transferase and reduced glutathione; increased levels
      of TBARS), impaired oral glucose tolerance and elevated HbA1C. Spirulina
      fusiformis was able to normalize the above mentioned parameters. Significant
      histopathological changes were found in the pancreas, liver and kidney sections
      of the diabetic control group while treatment with Spirulina fusiformis was able
      to minimize the extent of tissue damage. Current study shows that Spirulina
      fusiformis possesses significant antidiabetic and antihyperlipidemic effects in
      streptozotocin-induced diabetic rats by effectively reducing the rise in blood
      glucose levels and lipid profile.

PMID- 29450120
TI  - Anaerobic digestion of sulphate-rich post-tanning wastewater at different
      COD/sulphate and F/M ratios.
AB  - Anaerobic digestion of post-tanning wastewater was performed in batch anaerobic
      digester to evaluate the effect of COD/sulphate ratio [0.62, 0.69, and 1.20 (w/w)
      %] and F/M ratio [0.2, 0.3, 0.5, 0.7, 0.9, 1.1, 1.3, and 1.5 (w/w) %)] on the
      removal efficiency of COD. The F/M ratio of 0.3 was found to be the optimum ratio
      for the removal of COD by 53, 57, and 65%, respectively at COD/sulphate ratio of
      0.62, 0.69, and 1.20. The maximum sulphate removal was observed at F/M ratio of
      0.2 and the removal efficiency was 48, 50, and 58% at COD/sulphate ratio of 0.62,
      0.69, and 1.20, respectively. The removal efficiency of COD and sulphate was
      increased with increase in COD/sulphate ratio from 0.62 to 1.20 and decreased
      with increase in F/M ratio from 0.2 to 1.5 in anaerobic digestion of post-tanning
      wastewater. The maximum concentration of sulphide formation was 784 mg/L at
      COD/sulphate ratio of 0.62 in anaerobic digestion process and the process was
      inhibited at this sulphide concentration. The microbial activity in the sludge
      was evaluated through live and dead cell assay using fluorescent microscopy. The
      maximum amount of dead microbes was observed in the anaerobic digester, which was
      operated at COD/sulphate ratio of 0.62 than other studied ratio.

PMID- 29450121
TI  - Glyphosate induced toxicity to chickpea plants and stress alleviation by
      herbicide tolerant phosphate solubilizing Burkholderia cepacia PSBB1 carrying
      multifarious plant growth promoting activities.
AB  - In this study, strain PSBB1 isolated from Vicia faba rhizosphere was identified
      as Burkholderia cepacia, by 16S rDNA sequence analysis and characterized. Strain
      PSBB1 tolerated glyphosate up to 3200 MUg ml-1 and produced IAA (81.6 MUg ml-1),
      ACC deaminase (69.3 mg-1 protein h-1), SA (39.3 MUg ml-1) and 2,3-DHBA (26.6 MUg
      ml-1), solubilized insoluble P (50.8 MUg ml-1) and secreted 29.4 MUg ml-1
      exopolysaccharides, which decreased with increasing concentrations of glyphosate.
      Cell damage following glyphosate application was visible under SEM and CLSM. The
      phytotoxicity of glyphosate on chickpea was variable but significant. B. cepacia
      mitigated toxicity and enhanced the size, dry matter, symbiosis, seed attributes
      and nutritional contents of chickpea. Further, B. cepacia strain PSBB1 declined
      the levels of CAT, POD, APX and GPX and MDA contents at 4332 MUg kg-1 soil
      glyphosate. Proline also increased under glyphosate stress but declined in B.
      cepacia inoculated plants. The ability to tolerate higher concentration of
      glyphosate, the capacity to secrete plant growth regulators even under herbicide
      stress and potential to reduce the level of proline and antioxidant enzymes makes
      B. cepacia as an interesting choice for enhancing chickpea production in soils
      contaminated even with herbicides.

PMID- 29450122
TI  - Methyl Perillate as a Highly Functionalized Natural Starting Material for
      Terephthalic Acid.
AB  - Renewable commodity chemicals can be generated from plant materials. Often
      abundant materials such as sugars are used for this purpose. However, these lack
      appropriate functionalities and, therefore, they require extensive chemical
      modifications before they can be used as commodity chemicals. The plant kingdom
      is capable of producing an almost endless variety of compounds, including
      compounds with highly appropriate functionalities, but these are often not
      available in high quantities. It has been demonstrated that it is possible to
      produce functionalized plant compounds on a large scale by fermentation in
      microorganisms. This opens up the potential to exploit plant compounds that are
      less abundant, but functionally resemble commodity chemicals more closely. To
      elaborate this concept, we demonstrate the suitability of a highly functionalized
      plant compound, methyl perillate, as a precursor for the commodity chemical
      terephthalic acid.

PMID- 29450123
TI  - Epidemiology and Treatment of Hepatitis B in Prisoners.
AB  - Purpose of Review: The review details recent literature reports regarding
      Hepatitis B Virus (HBV) and, in particular, Hepatitis B prevalence/incidence in
      incarcerated populations around the world. Furthermore, the review will summarize
      the national/international guidelines regarding HBV and look at diagnosis,
      vaccination, treatment, and linkage to care after release. Recent Findings: HBV
      affects prisoners at a much higher rate than the general populations. Many who
      are at increased risk for HBV infection are also at increased risk for
      incarceration. Incarcerated settings also have higher rates of HBV transmission.
      Summary: Incarcerated individuals should be immunized if they are not already
      immune to HBV. Increased access to safe injecting and tattoo paraphernalia,
      condoms, and personal hygiene equipment could reduce the spread of HBV and other
      blood-borne and sexually transmitted infections. Future research should focus on
      ways to prevent the spread of HBV and similar viruses in incarcerated settings in
      order to protect incarcerated individuals and the general public. Research on
      effective linkage to community HBV care following release is needed.

PMID- 29450124
TI  - Reflections on the Future of Epidemiology: How Students Can Inform Our Vision.

PMID- 29450125
TI  - Characterization of the activity of beta-galactosidase from Escherichia coli and
      Drosophila melanogaster in fixed and non-fixed Drosophila tissues.
AB  - beta-Galactosidase encoded by the Escherichia coli lacZ gene, is widely used as a
      reporter molecule in molecular biology in a wide variety of animals. beta
      Galactosidase retains its enzymatic activity in cells or tissues even after
      fixation and can degrade X-Gal, a frequently used colormetric substrate,
      producing a blue color. Therefore, it can be used for the activity staining of
      fixed tissues. However, the enzymatic activity of the beta-galactosidase that is
      ectopically expressed in the non-fixed tissues of animals has not been
      extensively studied. Here, we report the characterization of beta-galactosidase
      activity in Drosophila tissues with and without fixation in various experimental
      conditions comparing the activity of two evolutionarily orthologous beta
      galactosidases derived from the E. coli lacZ and Drosophila melanogaster DmelGal
      genes. We performed quantitative analysis of the activity staining of larval
      imaginal discs and an in vitro assay using larval lysates. Our data showed that
      both E. coli and Drosophila beta-galactosidase can be used for cell-type-specific
      activity staining, but they have their own preferences in regard to conditions.
      E. coli beta-galactosidase showed a preference for neutral pH but not for acidic
      pH compared with Drosophila beta-galactosidase. Our data suggested that both E.
      coli and Drosophila beta-galactosidase show enzymatic activity in the
      physiological conditions of living animals when they are ectopically expressed in
      a desired specific spatial and temporal pattern. This may enable their future
      application to studies of chemical biology using model animals.

PMID- 29450126
TI  - Structural properties of the linkers connecting the N- and C- terminal domains in
      the MocR bacterial transcriptional regulators.
AB  - Peptide inter-domain linkers are peptide segments covalently linking two adjacent
      domains within a protein. Linkers play a variety of structural and functional
      roles in naturally occurring proteins. In this work we analyze the sequence
      properties of the predicted linker regions of the bacterial transcriptional
      regulators belonging to the recently discovered MocR subfamily of the GntR
      regulators. Analyses were carried out on the MocR sequences taken from the phyla
      Actinobacteria, Firmicutes, Alpha-, Beta- and Gammaproteobacteria. The results
      suggest that MocR linkers display phylum-specific characteristics and unique
      features different from those already described for other classes of inter-domain
      linkers. They show an average length significantly higher: 31.8 +/- 14.3 residues
      reaching a maximum of about 150 residues. Compositional propensities displayed
      general and phylum-specific trends. Pro is dominating in all linkers. Dyad
      propensity analysis indicate Pro-Pro as the most frequent amino acid pair in all
      linkers. Physicochemical properties of the linker regions were assessed using
      amino acid indices relative to different features: in general, MocR linkers are
      flexible, hydrophilic and display propensity for beta-turn or coil conformations.
      Linker sequences are hypervariable: only similarities between MocR linkers from
      organisms related at the level of species or genus could be found with sequence
      searches. The results shed light on the properties of the linker regions of the
      new MocR subfamily of bacterial regulators and may provide knowledge-based rules
      for designing artificial linkers with desired properties.

PMID- 29450127
TI  - Mobile phones electromagnetic radiation and NAD+-dependent isocitrate
      dehydrogenase as a mitochondrial marker in asthenozoospermia.
AB  - NAD+-dependent Isocitrate Dehydrogenase (NAD+-IDH) could be one of the cell phone
      radiation targets. Enzyme activity alteration may lead to decline in sperm
      motility during radio-frequency electromagnetic waves (RF-EMW) exposure. The
      current case control study aimed to investigate the possible relationship between
      mitochondrial NAD+-IDH activity in human seminal plasma and sperm motility among
      asthenozoospermic cellular phone users. A total number of ninety idiopathic
      infertile males referred from the Department of Dermatology and Andrology, were
      enrolled in this study. NAD+-IDH activity was measured in human seminal plasma by
      spectrophotometer. Computer-aided sperm analysis (CASA) following WHO criteria
      has been used for semen analyses. The results showed that IDH activity was
      increased in patients with prolonged cell phone daily use >=4 h/day. Its level,
      correlated negatively with either the motility ratio percentages (r = -0.46, p <
      0.001) or the progressive motility percentages (r = -0.50, p < 0.001) in the
      study groups. The current study suggests that NAD+-IDH in human seminal plasma
      could be one of seminal plasma biomarkers reflecting the mitochondrial function
      of spermatozoa. Alteration of its level could reflect the defective motility of
      sperms among some cases of cellular phone users.

PMID- 29450128
TI  - Molecular characterization and analysis of the porcine NURR1 gene.
AB  - Orphan receptor NURR1 (also termed NR4A2) belongs to the nuclear receptor
      superfamily and functions as a regulatory factor of differentiation, migration,
      maturation and maintenance of mesencephalic dopaminergic neurons. NURR1 plays an
      important role in nigrostriatal dopamine neuron development and is therefore
      implicated in the pathogenesis of neurodegenerative diseases linked to the
      dopamine system of the midbrain. Here we report the isolation and
      characterization of porcine NURR1 cDNA. The NURR1 cDNA was RT-PCR cloned using
      NURR1-specific oligonucleotide primers derived from in silico sequences. The
      porcine NURR1 cDNA encodes a polypeptide of 598 amino acids, displaying a very
      high similarity with bovine, human and mouse (99%) NURR1 protein. Expression
      analysis revealed a differential NURR1 mRNA expression in various organs and
      tissues. NURR1 transcripts could be detected as early as at 60 days of embryo
      development in different brain tissues. A significant increase in NURR1
      transcript in the cerebellum and a decrease in NURR1 transcript in the basal
      ganglia was observed during embryo development. The porcine NURR1 gene was mapped
      to chromosome 15. Two missense mutations were found in exon 3, the first coding
      exon of NURR1. Methylation analysis of the porcine NURR1 gene body revealed a
      high methylation degree in brain tissue, whereas methylation of the promoter was
      very low. A decrease in DNA methylation in a discrete region of the NURR1
      promoter was observed in pig frontal cortex during pig embryo development. This
      observation correlated with an increase in NURR1 transcripts. Therefore,
      methylation might be a determinant of NURR1 expression at certain time points in
      embryo development.

PMID- 29450129
TI  - Thyroid and reproductive hormones disruption as well as kallikrein-3 level in
      dimethyl nitrosamine-induced toxicity: Effects of ascorbate treatment in male
      wistar rats.
AB  - Information on dimethyl nitrosamine (DMN)-induced toxicity on endocrine functions
      is still scanty. This study therefore investigated the outcomes of DMN-induced
      toxicity on endocrine (thyroid and reproductive) functions, as well as kallikrein
      3 level, and effects of ascorbate treatments in male wistar rats. Thirty animals
      divided into six groups of five rats each were used. Group I animals were the
      normal control, group II animals served as vehicle control and were administered
      a single intraperitoneal dose of normal saline, groups III and IV were
      intraperitoneally injected with a single dose of 30 mg/kg DMN for 48 h, but group
      IV animals were post-treated orally with 5.71 mg/kg body weight (400 mg/70 kg)
      ascorbate for seven days, group V animals were pre-treated with same dose of
      ascorbate orally for seven days before intraperitoneal injection of DMN, while
      group VI animals were orally administered ascorbate only for seven days. Compared
      with control, DMN administration resulted in significant decrease (p < 0.05) in
      serum total cholesterol, testosterone (TST), luteinizing hormone (LH), free
      triiodothyronine (fT3), and kallikrein III (KLK-3) levels, as well as non
      significant increase in serum thyroid stimulating hormone (TSH) level. Pre
      treatment with ascorbate significantly increase LH and KLK-3 levels, while post
      treatment significantly increase fT3 level. Also, pre-treatment with ascorbate
      significantly reduced TSH level, while there was no significant difference in TST
      level following ascorbate treatments. From our findings and to some extent,
      ascorbate demonstrates ameliorative effects against DMN-induced hormonal
      disruption in male wistar rats, and this may be attributed to its antioxidant
      property.

PMID- 29450130
TI  - Mobile phones electromagnetic radiation and NAD+-dependent isocitrate
      dehydrogenase as a mitochondrial marker in asthenozoospermia.

PMID- 29450131
TI  - Dimethyl-Benz(a)anthracene: A mammary carcinogen and a neuroendocrine disruptor.
AB  - Polycyclic Aromatic Hydrocarbons (PAHs) are potent carcinogens. Among these,
      dimethylbenz(a)anthracene (DMBA) is well known for its capacity to induce mammary
      carcinomas in female Sprague-Dawley (SD) rats. Ovariectomy suppresses the
      susceptibility of this model to DMBA, thus suggesting that the inducible action
      of the carcinogen depends on ovarian hormones. The promotion of DMBA-induced
      adenocarcinoma is accompanied by a series of neuroendocrine disruptions of both
      Hypothalamo-Pituitary-Gonadal (HPG) and Hypothalamo-Pituitary-Adrenal (HPA) axes
      and of the secretion of melatonin during the latency period of 2 months that
      precedes the occurrence of the first mammary tumor. The present review analyses
      the various neuroendocrine disruptions that occur along the HPG and the HPA axes,
      and the marked inhibitory effect of the carcinogen on melatonin secretion. The
      possible relationships between the neuroendocrine disruptions, which essentially
      consist in an increased pre-ovulatory secretion of 17beta-estradiol and
      prolactin, associated with a marked reduction of melatonin secretion, and the
      decrease in gene expression of the receptors for aryl-hydrocarbons receptor (AhR)
      and 17beta-estradiol (ERalpha; ERbeta) are also discussed.

PMID- 29450132
TI  - Green tea polyphenols affect invasiveness of human gastric MKN-28 cells by
      inhibition of LPS or TNF-alpha induced Matrix Metalloproteinase-9/2.
AB  - Several studies demonstrated a correlation between green tea consumption and a
      reduced cancer risk. Among different components, green tea polyphenols have been
      identified as molecules responsible for the beneficial effects showed by the
      green tea against oxidative stress and cell invasiveness. In this study, we
      investigated the effects of green tea polyphenol extracts (GTPs) in human gastric
      MKN-28 cell line. To this aim, we have first evaluated the effect of GTPs on
      oxidative stress induced cell injury. The pre-treatment with 10-4 M catechin
      equivalents of GTPs exerts a protective effect on xanthine-xanthine oxidase
      induced cell cytotoxicity, thus confirming the anti-oxidant properties of GTPs.
      The effect of GTPs was also extended to the invasive ability of MKN-28 cells
      stimulated with TNF-alpha or LPS, as pro-inflammatory factors. Migration and
      matrigel invasion assays demonstrated that GTPs exposure (10-6 M) prevents the
      increase in cell invasiveness induced by TNF-alpha or LPS. Finally, we have
      analyzed the effect of GTPs on the levels of Matrix Metalloproteinases (MMP)-9/2,
      whose expression is up-regulated by TNF-alpha or LPS. Our results indicated that
      the pre-treatment with GTPs was able to reduce MMP-9/2 expression at both protein
      and enzyme activity levels in the conditioned media of TNF-alpha or LPS
      stimulated MKN-28 cells. In conclusion, our results demonstrated that green tea
      polyphenol extract reduces the invasiveness of gastric MKN-28 cancer cells
      through the reduction of TNF-alpha or LPS induced MMP-9/2 up-regulation.
      Therefore, these data support the hypothesis that GTPs could exert a protective
      role against the metastatic process in gastric cancer.

PMID- 29450133
TI  - Inhibition of the MAPK pathway alone is insufficient to account for all of the
      cytotoxic effects of naringenin in MCF-7 breast cancer cells.
AB  - Estrogen receptor (ER) antagonists such as tamoxifen (Tam) have been used
      successfully to treat ER+ breast cancers for more than 30 years. Unfortunately,
      long term use of Tam can result in resistance. Tam resistance is associated with
      the activation of growth factor signaling pathways that promote cell
      proliferation and survival. The mitogen-activated protein kinase (MAPK), is up
      regulated in Tam resistant (Tam-R) cells. Previous studies have reported that the
      flavanone, naringenin (Nar) can inhibit cell proliferation and induce apoptosis
      in ER+ breast cancer cells. Furthermore, Nar has been shown to inhibit the MAPK
      signaling pathways in MCF-7 cells. In this report we investigated whether
      inhibition of MAPK alone is mediating the effects of Nar on cell proliferation
      and viability. These studies will determine the mechanism of action of Nar. Tam-R
      MCF-7 breast cancer cells were treated with Nar or U0126, a MAPK kinase
      inhibitor. Our studies show that while both U0126 and Nar impaired cell
      proliferation and viability the combination of U0126 and Nar resulted in greater
      inhibition of cell viability than either compound alone. It has been previously
      reported that Nar can bind the ER. Our lab has also shown that Nar localizes
      ERalpha to a peri-nuclear region of the cell. Confocal microscopy revealed that
      in U0126 treated cells ERalpha displayed an even distribution across the
      cytoplasm as seen in untreated Tam-R cells. These studies suggest that MAPK is
      not the only target of Nar.

PMID- 29450134
TI  - CRISPR/Cas9-mediated target validation of the splicing inhibitor Pladienolide B.
AB  - CRISPR/Cas9 system confers molecular immunity in archeal and bacterial species
      against invading foreign nucleic acids. CRISPR/Cas9 system is used for genome
      engineering applications across diverse eukaryotic species. In this study, we
      demonstrate the utility of the CRISPR/Cas9 genome engineering system for drug
      target validation in human cells. Pladienolide B is a natural macrolide with
      antitumor activities mediated through the inhibition of pre-mRNA splicing. To
      validate the spliceosomal target of Pladienolide B, we employed the CRSIPR/Cas9
      system to introduce targeted mutations in the subunits of the SF3B complex in the
      HEK293T cells. Our data reveal that targeted mutagenesis of the SF3b1 subunit
      exhibited higher levels of resistance to Pladienolide B. Therefore, our data
      validate the spliceosomal target of Pladienolide B and provide a proof of concept
      on using the CRISPR/Cas9 system for drug target identification and validation.

PMID- 29450135
TI  - Development of a specific index to detect malnutrition in athletes: Validity in
      weight class or intermittent fasted athletes.
AB  - Fasted or weight-category athletes manage their training under strict diet
      conditions that could impair the stress-recovery balance and result in acute or
      chronic fatigue. However, to date, no validated biomarker are available to
      quantify this phenomena. The aim of this study was to assess the validity of a
      specific index combining plasma albumin and weight change to detect nutrition
      related risks of fatigue increase and under-performance in athletes experiencing
      particular nutritional conditions. An athlete's nutrition risk index (ANRI)
      equation, based on data from lightweight and heavyweight rowers, was developed
      using relationship between plasma albumin concentrations combined to weight
      changes with sport performance and overtraining scores and was tested by odds
      ratio for failure. The accuracy and sensitivity of this former specific equation
      was subsequently tested on runners observing the Ramadan-fasting as well as on
      boxers after a short weight-loss period. Independently of training and
      performance, lightweight rowers presented lower nutritional parameters than
      heavyweight (albumin: 37.4 +/- 2.7 vs 39.9 +/- 1.8 g.L-1, P < 0.05; weight state:
      94.5 +/- 1.8 vs 99.9 +/- 0.9%, P < 0.01). In lightweight, ANRI was related with
      overtraining score (R2 = 0.21, P < 0.01), risks for failure in competition were
      enhanced when ANRI increased (OR:2.5, P = 0.03). Relationship of ANRI with
      overtraining score tended to be also significant in runners (R2 = 0.32, P = 0.06)
      but not in boxers (P = 0.4). Albumin concentrations combined to weight loss
      appeared relevant to delineate nutrition-related risks of fatigue and/or
      competitive failure associated with mid-term diets (about 30 days) as observed in
      rowers and Ramadan-fasted runners. ANRI may benefit to athletes monitoring by
      delineating effects of their weight loss program.

PMID- 29450136
TI  - Initiative action of tumor-associated macrophage during tumor metastasis.
AB  - Tumor-associated macrophages (TAMs) are a significant component of the
      microenvironment of any solid tumors in the majority of cancers, associated with
      unfavorable prognosis. TAMs emerge as attractive targets for therapeutic
      strategies aimed at reprogramming their protumor phenotype into an effective
      antitumor activity. In this review article, we present an overview of mechanisms
      responsible for TAMs recruitment and highlight the roles of TAMs in the
      regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and
      chemotherapeutic resistance. We describe the interplay between Th17 cells and
      other immune cells in the tumor microenvironment, and we assess both the
      potential antitumorigenic and pro-tumorigenic activities of Th17 cells and their
      associated cytokines. Understanding the nature of Th17 cell responses in the
      tumor microenvironment will be important for the design of more efficacious
      cancer immunotherapies. Finally, we discuss TAM-targeting therapy as a promising
      novel strategy for an indirect cancer therapy.

PMID- 29450137
TI  - Liver and Metformin: Lessons of a fructose diet in mice.
AB  - Studies show that the continuous consumption of fructose can lead to nonalcoholic
      fatty liver disease (NAFLD) and steatohepatitis. We aimed to investigate the role
      of Metformin in an animal model of liver injury caused by fructose intake,
      focusing on the molecular markers of lipogenesis, beta-oxidation, and antioxidant
      defenses. Male three months old C57BL/6 mice were divided into control group (C)
      and fructose group (F, 47% fructose), maintained for ten weeks. After, the groups
      received Metformin or vehicle for a further eight weeks: control (C), control +
      Metformin (CM), fructose (F), and fructose + Metformin (FM). Fructose resulted in
      hepatic steatosis, insulin resistance and lower insulin sensitivity in
      association with higher mRNA levels of proteins linked with de novo lipogenesis
      and increased lipid peroxidation. Fructose diminished mRNA expression of
      antioxidant enzymes, and of proteins responsible for mitochondrial biogenesis.
      Metformin reduced de novo lipogenesis and increased the expression of proteins
      related to mitochondrial biogenesis, thereby increasing beta-oxidation and
      decreasing lipid peroxidation. Also, Metformin upregulated the expression and
      activity of antioxidant enzymes, providing a defense against increased reactive
      oxygen species generation. Therefore, a significant reduction in triglyceride
      accumulation in the liver, steatosis and lipid peroxidation was observed in the
      FM group. In conclusion, fructose increases de novo lipogenesis, reduces the
      antioxidant defenses, and diminishes mitochondrial biogenesis. After an extended
      period of fructose intake, Metformin treatment, even in continuing the fructose
      intake, can reverse, at least partially, the liver injury and prevents NAFLD
      progression to more severe states.

PMID- 29450138
TI  - Biological activities of frankincense essential oil in human dermal fibroblasts.
AB  - Although frankincense essential oil (FREO) has become increasingly popular in
      skin care, research on its biological activities in human skin cells is scarce,
      if not completely absent. In the current study, we explored the biological
      activities of FREO in pre-inflamed human dermal fibroblasts by analyzing the
      levels of 17 important protein biomarkers pertinent to inflammation and tissue
      remodeling. FREO exhibited robust anti-proliferative activity in these skin
      cells. It also significantly inhibited collagen III, interferon gamma-induced
      protein 10, and intracellular cell adhesion molecule 1. We also studied its
      effect in regulating genome-wide gene expression. FREO robustly modulated global
      gene expression. Furthermore, Ingenuity(r) Pathway Analysis showed that FREO
      affected many important signaling pathways that are closely related to
      inflammation, immune response, and tissue remodeling. This study provides the
      first evidence of the biological activities of FREO in human dermal fibroblasts.
      Consistent with existing studies in other models, the current study suggests that
      FREO possesses promising potential to modulate the biological processes of
      inflammation and tissue remodeling in human skin. Further research into the
      biological mechanisms of action of FREO and its major active components is
      recommended.

PMID- 29450139
TI  - The nature of the rate-limiting step of blue multicopper oxidases: Homogeneous
      studies versus heterogeneous.
AB  - Multicopper oxidases (MCOs) catalyzed two half reactions (linked by an
      intramolecular electron transfer) through a Ping-Pong mechanism: the substrate
      oxidation followed by the O2 reduction. MCOs have been characterized in details
      in solution or immobilized on electrode surfaces. The nature of the rate-limiting
      steps, which is controversial in the literature, is discussed in this mini review
      for both cases. Deciphering such rate-limiting steps is of particular importance
      to efficiently use MCOs in any applications requiring the reduction of O2 to
      water.

PMID- 29450140
TI  - JNK3 phosphorylates Bax protein and induces ability to form pore on bilayer lipid
      membrane.
AB  - Bax is a pro-apoptotic cytosolic protein. In this work native (unphosphorylated)
      and JNK3 phosphorylated Bax proteins are studied on artificial bilayer membranes
      for pore formation. Phosphorylated Bax formed pore on the bilayer lipid membrane
      whereas native one does not. In cells undergoing apoptosis the pore formed by the
      phosphorylated Bax could be important in cytochrome c release from the
      mitochondrial intermembrane space to the cytosol. The low conductance (1.5 nS) of
      the open state of the phosphorylated Bax pore corresponds to pore diameter of 0.9
      nm which is small to release cytochrome c (~3.4 nm). We hypothesized that JNK3
      phosphorylated Bax protein can form bigger pores after forming complexes with
      other mitochondrial proteins like VDAC, t-Bid etc. to release cytochrome c.

PMID- 29450141
TI  - Putative roles of mitochondrial Voltage-Dependent Anion Channel, Bcl-2 family
      proteins and c-Jun N-terminal Kinases in ischemic stroke associated apoptosis.
AB  - There is a constant need for better stroke treatments. Neurons at the periphery
      of an ischemic stroke affected brain tissue remains metabolically active for
      several hours or days after stroke onset. They later undergo mitochondrion
      mediated apoptosis. It has been found that inhibiting apoptosis in the peripheral
      ischemic neurons could be very effective in the prevention of stroke progression.
      During stroke associated apoptosis, cytosolic c-Jun N-terminal Kinases (JNKs) and
      Bcl-2 family proteins translocate towards mitochondria and promote cytochrome c
      release by interacting with the outer mitochondrion membrane associated proteins.
      This review provides an overview of the plausible interactions of the outer
      mitochondrial membrane Voltage Dependent Anion Channel, Bcl-2 family proteins and
      JNKs in cytochrome c release in the peripheral ischemic stroke associated
      apoptotic neurons. The review ends with a note on designing new anti-stroke
      treatments.

PMID- 29450142
TI  - Arborvitae (Thuja plicata) essential oil significantly inhibited critical
      inflammation- and tissue remodeling-related proteins and genes in human dermal
      fibroblasts.
AB  - Arborvitae (Thuja plicata) essential oil (AEO) is becoming increasingly popular
      in skincare, although its biological activity in human skin cells has not been
      investigated. Therefore, we sought to study AEO's effect on 17 important protein
      biomarkers that are closely related to inflammation and tissue remodeling by
      using a pre-inflamed human dermal fibroblast culture model. AEO significantly
      inhibited the expression of vascular cell adhesion molecule 1 (VCAM-1),
      intracellular cell adhesion molecule 1 (ICAM-1), interferon gamma-induced protein
      10 (IP-10), interferon-inducible T-cell chemoattractant (I-TAC), monokine induced
      by interferon gamma (MIG), and macrophage colony-stimulating factor (M-CSF). It
      also showed significant antiproliferative activity and robustly inhibited
      collagen-I, collagen-III, plasminogen activator inhibitor-1 (PAI-1), and tissue
      inhibitor of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2). The inhibitory effect
      of AEO on increased production of these protein biomarkers suggests it has anti
      inflammatory property. We then studied the effect of AEO on the genome-wide
      expression of 21,224 genes in the same cell culture. AEO significantly and
      diversely modulated global gene expression. Ingenuity pathway analysis (IPA)
      showed that AEO robustly affected numerous critical genes and signaling pathways
      closely involved in inflammatory and tissue remodeling processes. The findings of
      this study provide the first evidence of the biological activity and beneficial
      action of AEO in human skin cells.

PMID- 29450144
TI  - Anti-inflammatory, tissue remodeling, immunomodulatory, and anticancer activities
      of oregano (Origanum vulgare) essential oil in a human skin disease model.
AB  - The use of oregano (Origanum vulgare) essential oil (OEO) has become popular in
      skin care products. However, scientific research regarding its effects on human
      skin cells is scarce. In this study, we investigated the biological activity of a
      commercially available OEO, which is high in carvacrol content, in a human skin
      cell disease model. OEO induced marked antiproliferative effects and
      significantly inhibited several inflammatory biomarkers, including monocyte
      chemoattractant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1),
      intracellular cell adhesion molecule 1 (ICAM-1), interferon gamma-induced protein
      10 (IP-10), interferon-inducible T-cell alpha chemoattractant (I-TAC), and
      monokine induced by gamma interferon (MIG). OEO also significantly inhibited
      tissue remodeling biomarkers, namely collagen I, collagen III, epidermal growth
      factor receptor (EGFR), matrix metalloproteinase 1 (MMP-1), plasminogen activator
      inhibitor 1 (PAI-1), tissue inhibitor of metalloproteinase (TIMP) 1 and 2. An
      immunomodulatory biomarker, macrophage colony-stimulating factor (M-CSF), was
      also strongly inhibited by OEO treatment. In addition, OEO significantly
      modulated global gene expression and altered signaling pathways, many of which
      are critical in inflammation, tissue remodeling, and cancer signaling processes.
      These findings along with existing studies largely support the anti-inflammatory,
      tissue remodeling, immunomodulatory, and anticancer activities of OEO. In
      conclusion, this study provides the first evidence of the biological activity of
      OEO in human dermal fibroblasts. We suggest that OEO, with carvacrol as the major
      active component, is a promising candidate for use in skin care products with
      anti-inflammatory and anticancer properties.

PMID- 29450143
TI  - Purified horse milk exosomes contain an unpredictable small number of major
      proteins.
AB  - Exosomes are 40-100 nm nanovesicles containing RNA and different proteins.
      Exosomes containing proteins, lipids, mRNAs, and microRNAs are important in
      intracellular communication and immune function. Exosomes from different sources
      are usually obtained by combination of centrifugation and ultracentrifugation and
      according to published data can contain from a few dozens to thousands of
      different proteins. Crude exosome preparations from milk of eighteen horses were
      obtained for the first time using several standard centrifugations. Exosome
      preparations were additionally purified by FPLC gel filtration. Individual
      preparations demonstrated different profiles of gel filtration showing well or
      bad separation of exosome peaks and one or two peaks of co-isolating proteins and
      their complexes. According to the electron microscopy, well purified exosomes
      displayed a typical exosome-like size (30-100 nm) and morphology. It was shown
      that exosomes may have several different biological functions, but detection of
      their biological functions may vary significantly depending on the presence of
      exosome contaminating proteins and proteins directly into exosomes. Exosome
      proteins were identified before and after gel filtration by MALDI MS and MS/MS
      spectrometry of protein tryptic hydrolyzates derived by SDS PAGE and 2D
      electrophoresis. The results of protein identification were unexpected: one or
      two peaks co-isolating proteins after gel-filtration mainly contained kappa-,
      beta-, alpha-S1-caseins and its precursors, but these proteins were not found in
      well-purified exosomes. Well-purified exosomes contained from five to eight
      different major proteins: CD81, CD63 receptors, beta-lactoglobulin and
      lactadherin were common to all preparations, while actin, butyrophilin,
      lactoferrin, and xanthine dehydrogenase were found only in some of them. The
      article describes the morphology and the protein content of major horse milk
      exosomes for the first time. Our results on the decrease of major protein number
      identified in exosomal preparations after gel filtration may be important to the
      studies of biological functions of pure exosomes.

PMID- 29450145
TI  - Phosphorylation of purified mitochondrial Voltage-Dependent Anion Channel by c
      Jun N-terminal Kinase-3 modifies channel voltage-dependence.
AB  - Voltage-Dependent Anion Channel (VDAC) phosphorylated by c-Jun N-terminal Kinase
      3 (JNK3) was incorporated into the bilayer lipid membrane. Single-channel
      electrophysiological properties of the native and the phosphorylated VDAC were
      compared. The open probability versus voltage curve of the native VDAC displayed
      symmetry around the voltage axis, whereas that of the phosphorylated VDAC showed
      asymmetry. This result indicates that phosphorylation by JNK3 modifies voltage
      dependence of VDAC.

PMID- 29450146
TI  - Novel proteins from proteomic analysis of the trunk disease fungus Lasiodiplodia
      theobromae (Botryosphaeriaceae).
AB  - Many basic science questions remain regarding protein functions in the pathogen:
      host interaction, especially in the trunk disease fungi family, the
      Botryosphaeriaceae, which are a global problem for economically important plants,
      especially fruiting trees. Proteomics is a highly useful technology for studying
      protein expression and for discovering novel proteins in unsequenced and poorly
      annotated organisms. Current fungal proteomics approaches involve 2D SDS-PAGE and
      extensive, complex, protein extraction methodologies. In this work, a modified
      Folch extraction was applied to protein extraction to perform both de novo
      peptide sequencing and peptide fragmentation analysis/protein identification of
      the plant and human fungal pathogen Lasiodiplodia theobromae. Both bioinformatics
      approaches yielded novel peptide sequences from proteins produced by L.
      theobromae in the presence of exogenous triglycerides and glucose. These proteins
      and the functions they may possess could be targeted for further functional
      characterization and validation efforts, due to their potential uses in
      biotechnology and as new paradigms for understanding fungal biochemistry, such as
      the finding of allergenic enolases, as well as various novel proteases, including
      zinc metalloproteinases homologous to those found in snake venom. This work
      contributes to genomic annotation efforts, which, hand in hand with genomic
      sequencing, will help improve fungal bioinformatics databases for future studies
      of Botryosphaeriaceae. All data, including raw data, are available via the
      ProteomeXchange data repository with identifier PXD005283. This is the first
      study of its kind in Botryosphaeriaceae.

PMID- 29450147
TI  - Lemongrass (Cymbopogon flexuosus) essential oil demonstrated anti-inflammatory
      effect in pre-inflamed human dermal fibroblasts.
AB  - Lemongrass (Cymbopogon flexuosus) essential oil (LEO), which has citral as its
      main component, has exhibited anti-inflammatory effect in both animal and human
      cells. In this study, we evaluated the anti-inflammatory activity of a
      commercially available LEO in pre-inflamed human dermal fibroblasts. We first
      studied the impact of LEO on 17 protein biomarkers that are critically associated
      with inflammation and tissue remodeling. LEO significantly inhibited production
      of the inflammatory biomarkers vascular cell adhesion molecule 1 (VCAM-1),
      interferon gamma-induced protein 10 (IP-10), interferon-inducible T-cell alpha
      chemoattractant (I-TAC), and monokine induced by gamma interferon (MIG);
      decreased levels of the tissue remodeling biomarkers collagen-I and III,
      epidermal growth factor receptor (EGFR), and plasminogen activator inhibitor (PAI
      1); and inhibited the immunomodulatory biomarker macrophage colony-stimulating
      factor (M-CSF). Furthermore, we studied the impact of LEO on genome-wide gene
      expression profiles. LEO significantly modulated global gene expression and
      robustly impacted signaling pathways, many of which are critical for inflammation
      and tissue remodeling processes. This study provides the first evidence of the
      anti-inflammatory activity of LEO in human skin cells and indicates that it is a
      good therapeutic candidate for treating inflammatory conditions of the skin.

PMID- 29450148
TI  - The effect of endurance training with and without vitamin E on expression of p53
      and PTEN tumor suppressing genes in prostate glands of male rats.
AB  - The aim of this study was to investigate the effect of endurance training with
      and without vitamin E on the expression of p53 and Phosphatase and tension
      homolog (PTEN) tumor suppressor genes of prostate glands in male rats. For this
      purpose, 50 Sprague-Dawley male rats were randomly assigned into 5 groups: (1)
      control group (CON, n = 10), (2) sham (S, n = 10), (3) endurance training (ET, n
      = 10), (4) endurance training + vitamin E (ET + VE, n = 10), (5) vitamin E (VE, n
      = 10). Endurance training protocol was implemented for 6 weeks, 6 days per week,
      in accordance with the overload principle. To measure expression changes of p53
      and PTEN genes in rats' prostate, real-time PCR method was used and HPLC method
      was used to measure vitamin E in this tissue. After 6 weeks of taking vitamin E,
      its level in all groups, except for group VE (p < 0.000) did not significantly
      increase. After implementing training protocol, p53 expression reduced
      significantly in ET group (p < 0.026). Vitamin E supplementation along with
      endurance training did not cause any significant change either p53 or PTEN
      (respectively; p < 0.2, p < 0.11). Instead, vitamin E supplementation without
      endurance training caused significant increase in PTEN, but did not cause any
      significant changes in p53 (respectively; p < 0.016, p < 0.15). These results
      indicate that endurance training reduces p53 and PTEN tumor suppressing genes
      expression, and taking vitamin E supplement could increase expression of these
      genes in some extent.

PMID- 29450149
TI  - Human and mouse microarrays-guided expression analysis of membrane protein
      trafficking-related genes in MDCK cells, a canine epithelial model for apical and
      basolateral differential protein targeting.
AB  - MDCK cells are widely used to study the differential targeting of membrane
      transporters to apical and basolateral membrane but its canine origin limited the
      commercial tools available for the analysis of protein trafficking machinery.
      Because apical and basolateral membranes are only found in differentiated
      epithelial cells, genes critical for differential targeting may be specifically
      up-regulated upon MDCK cell differentiation. To search for these genes, a cross
      species screening strategy was used. We first analyzed the human microarray data
      for protein trafficking-related genes that were up-regulated in colon carcinoma
      Caco2 cells upon differentiation. The results of mouse 44K gene expression
      microarray analysis were then used to extract additional candidate genes that
      showed higher expression in normal colon epithelium compared to primary embryonic
      fibroblasts. Finally, NCBI genomic sequence information was used to design RT-PCR
      primers for 13 candidate and 10 negative control genes and used to analyze MDCK
      cells at 2, 13 and 17 days after seeding. To determine whether the gene up
      regulation was specific in epithelial differentiation, we also performed RT-PCR
      on rat non-differentiating intestinal IEC-6 cells and mouse C2C12 cells, a
      differentiating myoblast model. Of the 13 candidate genes, 3 genes, SDCBP2,
      KIF12, KIF27, met all criteria of specific up-regulation in differentiated MDCK
      cells. In addition, KIF13A showed up-regulation in differentiated MDCK and C2C12
      cells but not in IEC-6 cells cultured for the same duration. The functions of
      these genes need to be analyzed in the future. This cross-species screening
      strategy may be useful for other non-human, non-rodent cell models.

PMID- 29450150
TI  - Chemical composition analysis and in vitro biological activities of ten essential
      oils in human skin cells.
AB  - Research on the biological effects of essential oils on human skin cells is
      scarce. In the current study, we primarily explored the biological activities of
      10 essential oils (nine single and one blend) in a pre-inflamed human dermal
      fibroblast system that simulated chronic inflammation. We measured levels of
      proteins critical for inflammation, immune responses, and tissue-remodeling
      processes. The nine single oils were distilled from Citrus bergamia (bergamot),
      Coriandrum sativum (cilantro), Pelargonium graveolens (geranium), Helichrysum
      italicum (helichrysum), Pogostemon cablin (patchouli), Citrus aurantium
      (petitgrain), Santalum album (sandalwood), Nardostachys jatamansi (spikenard),
      and Cananga odorata (ylang ylang). The essential oil blend (commercial name
      Immortelle) is composed of oils from frankincense, Hawaiian sandalwood, lavender,
      myrrh, helichrysum, and rose. All the studied oils were significantly anti
      proliferative against these cells. Furthermore, bergamot, cilantro, and spikenard
      essential oils primarily inhibited protein molecules related to inflammation,
      immune responses, and tissue-remodeling processes, suggesting they have anti
      inflammatory and wound healing properties. Helichrysum and ylang ylang essential
      oils, as well as Immortelle primarily inhibited tissue remodeling-related
      proteins, suggesting a wound healing property. The data are consistent with the
      results of existing studies examining these oils in other models and suggest that
      the studied oils may be promising therapeutic candidates. Further research into
      their biological mechanisms of action is recommended. The differential effects of
      these essential oils suggest that they exert activities by different mechanisms
      or pathways, warranting further investigation. The chemical composition of these
      oils was analyzed using gas chromatography-mass spectrometry.

PMID- 29450151
TI  - Comparison of antimicrobial activities of natural essential oils and synthetic
      fragrances against selected environmental pathogens.
AB  - Plant essential oils (EOs) are known to inhibit the growth of bacteria and fungi.
      Whether these antimicrobial effects are comparable to synthetic household
      products is less clear. Furthermore, limited research is available on the
      potential additive effect of blending EOs. In this investigation, a new EO blend
      containing orange, patchouli, peppermint, and clary sage was compared to its
      individual single oils and to three household products-air freshener, liquid
      soap, and body spray-for their ability to inhibit the growth of Staphylococcus
      aureus, Streptococcus pneumoniae, Pseudonomas aeruginosa, and Aspergillus
      brasiliensis in the disc-diffusion assay. The new EO blend significantly
      inhibited the growth of the four microorganisms. The zones of inhibition of new
      EO blend were greater than the air freshener and similar to the liquid soap and
      body spray, with the exception of Str. pneumoniae in which the body spray
      provided greater inhibitory zone. The new EO blend and the single oils, with the
      exception of peppermint, equally inhibited the growth of S. aureus and Str.
      pneumoniae suggesting no additive effect. P. aeruginosa and A. brasiliensis
      showed variable susceptibility to all EOs except for no susceptibility to orange
      and limonene. No difference was found between (-) and (+)-limonene; whereas, (+)
      menthol showed greater effect than (-)-menthol. In conclusion, blending the EO of
      orange, patchouli, peppermint, and clary sage was beneficial in inhibiting the
      growth of S. aureus, Str. pneumoniae, P. aeruginosa, and A. brasiliensis
      providing a natural antimicrobial fragrance option over synthetics fragrances
      used in soaps, body sprays, and air fresheners.

PMID- 29450152
TI  - A welcome to the new journal, International Journal of Cardiology - Heart and
      Vessels (IJC-H + V).
AB  - A new journal has been launched: IJC - Heart and Vessels [1]. It builds upon the
      success of the main journal International Journal of Cardiology. As an
      introduction to the new journal we will be publishing a series of summaries of
      the topics to be covered, highlighting the most important papers in the field
      that have been published recently in the main journal, International Journal of
      Cardiology. This article describes a topic review of congenital heart disease.
      IJC has become one of the most important sources of quality papers in this field
      and many excellent publications have been published in the main journal. The
      expansion of space occasioned by the launch of IJC - Heart and Vessels will allow
      us to publish more high quality papers in the expanding field of congenital heart
      disease.

PMID- 29450153
TI  - Gender related predictors of limited exercise capacity in heart failure.
AB  - Aim: The aim of this study was to investigate the impact of gender on the
      prediction of limited exercise capacity in heart failure (HF) patients assessed
      by 6 minute walk test (6-MWT). Methods: In 147 HF patients (mean age 61 +/- 11
      years, 50.3% male), a 6-MWT and a Doppler echocardiographic study were performed
      in the same day. Conventional cardiac measurements were obtained and global LV
      dyssynchrony was indirectly assessed using total isovolumic time - t-IVT [in
      s/min; calculated as: 60 - (total ejection time - total filling time)] and Tei
      index (t-IVT/ejection time). Patients were divided into two groups according to
      gender, which were again divided into two subgroups based on the 6-MWT distance
      (Group I: <= 300 m, and Group II: > 300 m). Results: Female patients were younger
      (p = 0.02), and had higher left ventricular (LV) ejection fraction - EF (p =
      0.007) but with similar 6-MWT distance to male patients (p = 68). Group I male
      patients had lower hemoglobin level (p = 0.02) and lower EF (p = 0.03), compared
      with Group II, but none of the clinical or echocardiographic variables differed
      between groups in female patients. In multivariate analysis, only t-IVT [0.699
      (0.552-0.886), p = 0.003], and LV EF [0.908 (0.835-0.987), p = 0.02] in males,
      and NYHA functional class [4.439 (2.213-16.24), p = 0.02] in females
      independently predicted poor 6-MWT distance (< 300 m). Conclusion: Despite
      similar limited exercise capacity, gender determines the pattern of underlying
      cardiac disturbances; ventricular dysfunction in males and subjective NYHA class
      in female heart failure patients.

PMID- 29450154
TI  - Are ICD recipients able to foresee if they want to withdraw therapy or deactivate
      defibrillator shocks?
AB  - Background: Expert consensus statements on management of implantable cardioverter
      defibrillators (ICDs) emphasize the importance of having discussions about
      deactivation before and after implantation. These statements were developed with
      limited patient input. The purpose of this study was to identify the factors
      associated with patients' experiences of end-of-life discussions, attitudes
      towards such discussions, and attitudes towards withdrawal of therapy (i.e.,
      generator replacement and deactivation) at end-of-life, in a large national
      cohort of ICD-recipients. Methods: We enrolled 3067 ICD-patients, administrating
      the End-of-Life-ICD-Questionnaire. Results: Most (86%) had not discussed ICD
      deactivation with their physician. Most (69%) thought discussions were best at
      end-of-life, but 40% stated that they never wanted the physician to initiate a
      discussion. Those unwilling to discuss deactivation were younger, had experienced
      battery replacement, had a longer time since implantation, and had better quality
      of-life. Those with psychological morbidity were more likely to desire a
      discussion about deactivation. Many patients (39%) were unable to foresee what to
      decide about deactivation in an anticipated terminal condition. Women, those
      without depression, and those with worse ICD-related experiences were more
      indecisive about withdrawal of therapy. Irrespective of shock experiences, those
      who could take a stand regarding deactivation chose to keep shock therapies
      active in many cases (39%). Conclusions: Despite consensus statements
      recommending discussions about ICD-deactivation at the end-of-life, such
      discussion usually do not occur. There is substantial ambivalence and
      indecisiveness on the part of most ICD-patients in this nationwide survey about
      having these discussions and about expressing desires about deactivation in an
      anticipated end-of-life situation.

PMID- 29450155
TI  - Seven-year follow-up of percutaneous closure of patent foramen ovale.
AB  - Background: Observational studies favor percutaneous closure of patent foramen
      ovale (PFO) over medical treatment to reduce recurrent stroke while randomized
      trials fail to demonstrate significant superiority of percutaneous PFO closure.
      Few long-term studies are available post PFO closure. This study reports long
      term clinical outcomes after percutaneous PFO closure. Methods: Between 1997 and
      2006, 86 consecutive eligible patients with cerebrovascular events, presumably
      related to PFO, underwent percutaneous PFO closure. All 86 patients were invited
      to a long-term follow-up, which was carried out during 2011 and 2012. Results:
      Percutaneous PFO closure was successfully performed in 85 of 86 patients. The
      follow-up rate was 100%. No cardiovascular or cerebrovascular deaths occurred.
      Two patients (both women) died from lung cancer during follow-up. Follow-up
      visits were conducted for 64 patients and the remaining 20 patients were followed
      up by phone. The mean follow-up time was 7.3 years (5 to 12.4 years). Mean age at
      PFO closure was 49 years. One patient had a minor stroke one month after PFO
      closure and a transient ischemic attack (TIA) two years afterwards. One other
      patient suffered from a TIA six years after closure. No long-term device-related
      complications were observed. Conclusions: Percutaneous PFO closure was associated
      with very low risk of recurrent stroke and is suitable in most patients. We
      observed no mortality and no long-term device-related complications related to
      PFO closure, indicating that percutaneous PFO closure is a safe and efficient
      treatment even in the long term.

PMID- 29450156
TI  - Clinical Efficacy and Safety of SeQuent Please Paclitaxel-Eluting Balloon in a
      Real-World Single-Center Registry of South-East Asian Patients.
AB  - Background: Drug eluting balloon (DEB) is a new therapeutic option for treatment
      of obstructive coronary lesions in percutaneous coronary intervention (PCI).
      There is limited data on the safety and efficacy of DEB in Asian patients in
      contemporary clinical registries. We evaluated the clinical efficacy and safety
      of SeQuent Please paclitaxel-eluting balloon in our cohort of South-East Asian
      patients in real world clinical practice. Methods: Between January 2010 to
      November 2012, 320 patients (76% male, mean age 61.3 +/- 11.2 years) with a total
      of 337 coronary lesions were treated with SeQuent Please drug-eluting balloon
      (DEB). The primary endpoint was major adverse cardiac events (MACE) ie a
      composite of cardiovascular death, target vessel related myocardial infarction
      (MI) and target lesion revascularization (TLR) at 9 months follow-up. Results:
      The majority of patients presented with acute coronary syndrome (76%).The most
      common indication for the use of DEB was small vessel disease (54%) followed by
      instent restenosis (21%), bifurcation lesions (6%) and others (19%). An average
      of 1.23 +/- 0.5 DEB were used per patient, with mean DEB diameter of 2.6 +/- 0.6
      mm and average total length of 24.0 +/- 11.1 mm.At 9 months follow-up, 5.3% of
      patients developed MACE. MACE was mainly driven by TLR(4%) followed by target
      vessel related myocardial infarction (2.6%) and cardiovascular death (1%).
      Conclusion: SeQuent Please DEB was a safe and effective treatment modality in our
      cohort of South-East Asian patients with a low incidence of MACE observed at 9
      months follow-up.

PMID- 29450158
TI  - Associations between the consumption of different kinds of seafood and out-of
      hospital cardiac arrests of cardiac origin in Japan.
AB  - Background: Prospective cohort studies have shown that seafood consumption is
      inversely related to fatal coronary heart disease, sudden cardiac death and
      stroke. We studied whether the kind of seafood consumed in addition to seafood
      consumption per se is associated with out-of-hospital cardiac arrests (OHCA) of
      cardiac origin. Methods and results: We compared the average consumption of
      different kinds of seafood and other risk factors to the average incidence of age
      adjusted OHCA (660,672 cases of OHCA: 55.2% of cardiac origin and 44.8% of non
      cardiac origin) between 2005 and 2010 in the 47 prefectures of Japan. There were
      many significant correlations between the incidence of age-adjusted OHCA of
      cardiac origin (ad-OHCA-CO) and the consumption of many kinds of seafood, but not
      the total consumption of seafood. The consumption of horse mackerel (r = - 0.568,
      p < 0.0001) and saury (r = 0.607, p < 0.0001) showed the highest negative and
      positive correlations, respectively, with the age-adjusted incidence of ad-OHCA
      CO. Conclusions: In Japan, the consumption of different kinds of seafood may be
      an important factor in OHCA of cardiac origin. Thus, dietary habits with regard
      to seafood may play a role in OHCA of cardiac origin, however, the question of
      whether to eat fish in general or instead to eat certain kinds of fish is still
      unclear.

PMID- 29450159
TI  - Association between heart calcification assessed by echocardiography and future
      cardiovascular disease mortality and morbidity.
AB  - Background: Echocardiography can detect calcium deposits in heart valves and
      aortic root, but the relationship of echocardiographic heart calcification such
      as aortic valve calcification (AVC), mitral annular calcification (MAC), and
      aortic root calcification (ARC) with future cardiovascular disease (CVD)
      mortality and morbidity is not fully elucidated. Methods: We analyzed data from
      943 patients with suspected coronary heart disease (mean age, 65.7 years; 36%
      female). Echocardiographic total heart calcification (THC) score was determined
      by summing up the AVC, MAC, and ARC variables; THC-0 (N = 397), THC-1 (N = 236),
      THC-2 (N = 224), and THC-3 (N = 86). Subjects were followed for mean 2.9 years to
      assess the risk of death from CVD causes. Cardiovascular morbidity was defined as
      new episodes of non-fatal myocardial infarction, congestive heart failure,
      stroke, and surgical treatment of vascular disease. Results: There were 43 CVD
      deaths and a total of 160 CVD events. Kaplan-Meier curves showed a graded CVD
      mortality and morbidity across increasing THC score values. With full adjustment,
      Cox regression hazard ratios (95% confidence intervals) for CVD mortality and
      morbidity, using no calcification as reference, for THC-1, THC-2, and THC-3 were
      2.21 (1.31-3.74), 2.59 (1.53-4.39) and 4.14 (2.30-7.47), respectively. When THC
      score was added to models with CVD risk factors, C-statistics were significantly
      larger for CVD mortality (p = 0.048) and for CVD mortality and morbidity (p =
      0.004). Conclusions: THC score, the sum of the amounts of AVC, MAC, and ARC
      present as estimated by echocardiography, has an independent and incremental
      prognostic value in a high-risk population.

PMID- 29450157
TI  - Cardiac disease in children and young adults with various lysosomal storage
      diseases: Comparison of echocardiographic and ECG changes among clinical groups.
AB  - Background: Lysosomal storage disease (LSD) is a rare inherited disease group.
      Consecutively there are few data on cardiac changes in mucopolysaccharidosis
      (MPS), Anderson Fabry disease (AFD), and other LSD (oLSD) including Pompe disease
      (PD) and Danon disease (DD), I-cell disease ICD and mucolipidosis III (ML III).
      Methods: Between 1994 and 2011, we identified 39 patients with LSD: 25 with MPS,
      8 with AFD, and 6 with oLSD including PD (1), ML III (2), DD (1), and ICD (2) at
      our institution fulfilling the inclusion criteria of at least one echocardiogram
      and ECG. Results: Median age was 11.4 years (range: 2-27), 22 were females (56%).
      Normal echocardiograms were present in 12 patients (31%): 4 with MPS (16%), 7 AFD
      (88%), and 1 oLSD (17%). Valvular heart disease was present in 23 patients (59%)
      occurring more often in MPS (76%) and oLSD (67%) than in AFD (0%) (p < 0.001).
      The most common ECG abnormality was a short PR interval in 10 of 35 patients
      (29%) occurring in all LSD groups. Median follow-up was 5.8 (0.2-22.2) years
      showing diminished 5-year survival compared to an age-matched group. However, no
      patient died due to a cardiac cause and no cardiovascular intervention was
      necessary. Conclusion: Echocardiographically detectable cardiovascular
      involvement in children with LSD is mostly confined to MPS and oLSD. Valve
      thickening in echo and a short PR interval in the ECG are the most frequent
      abnormalities. Routine repeat assessment is recommended in LSD. However,
      significant cardiac disease necessitating cardiac intervention is rare during a
      short follow-up.

PMID- 29450160
TI  - Protease activated receptor-1, but not -2, -3 and -4, is the player in the
      pathogenesis of atrial fibrosis; The experiment by neonatal rat atrial
      fibroblasts.

PMID- 29450161
TI  - Early transcatheter heart valve thrombosis detected by multidetector computed
      tomography.

PMID- 29450162
TI  - The predictive value of arterial and valvular calcification for mortality and
      cardiovascular events.
AB  - A review of the predictive ability of arterial and valvular calcification has
      shown an additive effect of calcification in more than 1 location in predicting
      mortality and coronary heart disease, with mitral annual calcification being a
      particularly strong predictor. In individual arteries and valves there is a clear
      association between calcification presence, extent and progression and future
      cardiovascular events and mortality in asymptomatic, symptomatic and high risk
      patients, although adjustment for calcification in other arterial beds generally
      renders associations non-significant. Furthermore, in acute coronary syndrome,
      culprit plaque is normally not calcified. This would tend to reduce the validity
      of calcification as a predictor and suggest that the association with
      cardiovascular events and mortality may not be causal. The association with
      stroke is less clear; carotid and intracranial artery calcification show little
      predictive ability, with symptomatic plaques tending to be uncalcified.

PMID- 29450163
TI  - Mineralocorticoid receptor antagonist in heart failure: Past, present and future
      perspectives.
AB  - Aldosterone is involved in various deleterious effects on the cardiovascular
      system, including sodium and fluid retention, myocardial fibrosis, vascular
      stiffening, endothelial dysfunction, catecholamine release and stimulation of
      cardiac arrhythmias. Therefore, aldosterone receptor blockade may have several
      potential benefits in patients with cardiovascular disease. Mineralocorticoid
      receptor antagonists (MRAs) have been shown to prevent many of the maladaptive
      effects of aldosterone, in particular among patients with heart failure (HF).
      Randomized controlled trials have demonstrated efficacy of MRA in heart failure
      with reduced ejection fraction, both in patients with NYHA functional classes III
      and IV and in asymptomatic and mildly symptomatic patients (NYHA classes I and
      II). Recent data in patients with heart failure with preserved ejection fraction
      are encouraging. MRA could also have anti-arrhythmic effects on atrial and
      ventricular arrhythmias and may be helpful in patient ischemic heart disease
      through prevention of myocardial fibrosis and vascular damage. This article aims
      to discuss the pathophysiological effects of aldosterone in patients with
      cardiovascular disease and to review the current data that support the use of MRA
      in heart failure.

PMID- 29450164
TI  - Late gadolinium enhancement (LGE) progresses with right ventricle volume in
      children after repair of tetralogy of fallot.
AB  - Background: Fibrosis after myocardial damage can be determined by cardiac
      magnetic resonance (CMR) with late gadolinium enhancement (LGE). We studied
      whether ventricular LGE is visible in the ventricles of pediatric and adolescent
      TOF (tetralogy of Fallot) patients by measuring LGE and investigating whether
      fibrosis correlated with right ventricular volume, pulmonary regurgitation, N
      terminal pro-brain natriuretic peptide (NT-proBNP) or the aminoterminal
      propeptide of type III procollagen (PIIINP). We also studied if the patient's
      age, post-operative follow-up time or surgical history would affect LGE. Methods:
      A total of 40 pediatric patients who had undergone TOF repair and 43 healthy age
      and gender matched controls underwent a CMR study, whereby LGE was scored in the
      right (RV) and the left ventricle. To exclude the possible iatrogenic scarring we
      calculated the LGE score by excluding the right ventricular outflow tract and VSD
      patch region. Results: All patients had RV LGE and in 39 of 40 it was seen also
      outside the surgically affected areas. The amount of LGE correlated positively
      with the RV end-diastolic volume (r = 0.44, P = 0.0045), pulmonary regurgitation
      (r = 0.40, P = 0.013), and with NT-proBNP. The presence of LGE also depended on
      post-operative follow-up time (r = 0.53, P = 0.006). PIIINP levels of TOF
      patients were significantly higher than in the control subjects but it did not
      correlate with LGE or with any of the studied clinical markers. Conclusions: LGE
      is present globally in the right ventricular muscle in children and adolescents
      with TOF. The longer the follow-up time the more common was the LGE in the right
      ventricle.

PMID- 29450165
TI  - Difference of vascular response between everolimus- and paclitaxel-eluting stents
      for small coronary artery disease: Optical coherence tomography analysis.
AB  - Background: Previous clinical trials have demonstrated the clinical and
      angiographic superiority of everolimus-eluting stents (EES) compared with
      paclitaxel-eluting stents (PES) in the small coronary vessel. However, the
      differences of vascular response including assessment of morphological neointimal
      tissue (NIT) characteristics using optical coherence tomography (OCT) have not
      been fully evaluated. The aim of this study is to evaluate the differences of
      chronic vascular response following small coronary stenting between EES and PES
      using OCT. Methods and results: A prospective OCT examination at 9 month follow
      up was performed for 50 small coronary artery diseases (50 patients) treated by a
      single 2.5 mm stent for each stent group. Cross-sectional area within stent
      segments were analyzed at an interval of 1 mm. NIT structure (homogeneous or
      heterogeneous) was evaluated for qualitative assessment. Homogeneous NIT was
      observed significantly higher and heterogeneous NIT was lower in EES compared
      with PES (93% vs. 89%; p = 0.003, 6.5% vs. 10.3%; p = 0.002, respectively). The
      frequencies of exposed and malapposed struts were lower in EES compared with PES
      (0.2% vs. 1.7%; p = 0.0001, 0.1% vs. 0.3%; p = 0.001, respectively). NIT
      eccentricity index and NIT area were lower in EES compared with PES (0.69 +/-
      0.08 vs. 0.76 +/- 0.10; p = 0.001, 0.97 +/- 0.42 mm2 vs. 1.27 +/- 0.67 mm2; p =
      0.01, respectively). Conclusions: A favorable vascular response was observed
      after EES implantation compared with PES for small coronary artery disease. In
      addition, the characteristics of NIT after EES implantation were more stable than
      PES at 9 month follow-up.

PMID- 29450166
TI  - Progress of right ventricular dilatation in adults with repaired tetralogy of
      Fallot and free pulmonary regurgitation.
AB  - Background: The time course of progressive dilatation of the right ventricle (RV)
      in adults with pulmonary regurgitation (PR) late after repair of tetralogy of
      Fallot (TOF) is poorly characterized. Methods: We analysed cardiac MRI data (1.5
      T) from 14 adult repaired TOF patients (26 +/- 11 years of age) with dilated RVs
      and known significant PR, on 2 separate visits with a between MRI period of 2.1
      +/- 1.0 years. Results: Indexed RV end diastolic volume (RVEDVi) increased over 2
      years (142 +/- 19 to 151 +/- 20 mL/m2, p = 0.005; change = 8.4 +/- 9.3 mL/m2,
      range = - 6 to 26 mL/m2; annual mL/m2 increase = 4.3 +/- 4.6; annual percentage
      increase = 3.1 +/- 3.3%), whilst RV ejection fraction decreased (53 +/- 8 to 49
      +/- 7 %, p = 0.039). RV muscular corpus (RVMC) EDVi significantly increased (130
      +/- 19 to 138 +/- 20 mL/m2, p = 0.014), whereas RV outflow tract (RVOT) EDVi did
      not (12 +/- 7 vs 13 +/- 6 mL/m2, p = 0.390). No other RV or LV measures
      significantly changed during the inter-MRI period. The change in RVEDVi
      correlated significantly with LV end diastolic volume (r = - 0.582, p = 0.029),
      RVEDVi:LVEDVi (r = 0.6, p = 0.023) and RVMC EDVi (r = 0.9, p < 0.001) but not
      RVOT EDVi (r = 0.225, p = 0.459). Conclusions: Adult repaired TOF patients with
      free PR experienced a mean 3.1%, or 4.3 mL/m2, annual increase in RVEDVi,
      unrelated to the initial RVEDVi or PR fraction. The increase in RVEDVi was due to
      RVMC rather than RVOT dilatation. This provides a guide to the frequency of MR
      surveillance and insights into the natural history of progressive RV dilatation
      in this setting.

PMID- 29450167
TI  - Repair or prosthesis insertion in ischemic mitral regurgitation: Two faces of the
      same medal.
AB  - Objective: The proper treatment of chronic ischemic mitral regurgitation (CIMR)
      is still under evaluation. The different role of mitral valve repair (MVr) or
      mitral valve prosthesis insertion (MVPI) is still not defined. Methods: From May
      2009 to December 2011 167 patients with ejection fraction (EF) <= 40% had MV
      surgery for CIMR, MVr in 135 (80.8%) and MVPI in 32 (19.2%). Indication to MVPI
      was a MV coaptation depth > 10 mm. EF was lower (26 +/- 7 vs 32 +/- 6, p =
      0.0000) in MVPI, whereas MR grade (3.6 +/- 0.8 vs 2.7 +/- 0.9, p = 0.0000), left
      ventricle dimensions (end diastolic, LVEDD, 62 +/- 7 vs 57 +/- 6 mm, p = 0.0001;
      end systolic, LVESD, 49 +/- 8 vs 44 +/- 8 mm, p = 0.0018), systolic pulmonary
      artery pressure (51 +/- 22 vs 41 +/- 16 mm Hg, p = 0.0037) and NYHA Class (3.6 +/
      0.5 vs 2.8 +/- 0.6, p = 0.0000) were higher. Results: In-hospital mortality was
      similar (3.1 vs 3.7%) as well as 3-year survival (86 +/- 6 vs 88 +/- 4) and
      survival in NYHA Class I/II (80 +/- 5 vs 83 +/- 4). One hundred thirty nine
      patients had an echocardiographic evaluation after a minimum of 4 months (13 +/-
      8). EF rose significantly in both groups (from 26 +/- 7% to 30 +/- 4%, p =
      0.0122, and from 32 +/- 6% to 35 +/- 8%, p = 0.0018). LVESD reduced significantly
      in both groups (from 49 +/- 8 to 43 +/- 9 mm, p = 0.0109, and from 44 +/- 8 to 41
      +/- 7 mm, p = 0.0033). MR grade was significantly lower in patients who had MVPI
      (0.1 +/- 0.2 vs 0.3 +/- 0.3, p = 0.0011). Conclusions: With appropriate
      indications, MVPI is a safe procedure which provides similar results to MVr with
      lower MR return, even if addressed to patients with worse preoperative
      parameters.

PMID- 29450168
TI  - Guideline-directed medical therapy for secondary prevention after coronary artery
      bypass grafting in patients with depression.
AB  - Background: We hypothesized that depressed patients would have lower use of
      guideline-directed medical therapy for secondary prevention of cardiovascular
      events following coronary artery bypass grafting (CABG). Methods: We included all
      patients who underwent primary isolated CABG in Sweden between 2006 and 2008. We
      cross-linked individual level data from national Swedish registers. Preoperative
      depression was defined as at least one antidepressant prescription dispensed
      before surgery. We defined medication use as at least two dispensed prescriptions
      in each medication class (antiplatelet agents, beta-blockers, angiotensin
      converting enzyme inhibitors (ACEI)/angiotensin II receptor blocker (ARB), and
      statins) within a rolling 12 month period. We calculated adjusted risk ratios
      (RR) for the use of each medication class, and for all four classes, after one
      and four years, respectively. Results: During the first year after CABG, 93% of
      all patients (n = 10,586) had at least two dispensed prescriptions for an
      antiplatelet agent, 68% for an ACEI/ARB, 91% for a beta-blocker, and 92% for a
      statin. 57% had prescriptions for all four medication classes. After four years
      (n = 4034), 44% had filled prescriptions for all four medication classes.
      Preoperative depression was not significantly associated with a lower use of all
      four medication classes after one year (RR 0.98, 95% confidence interval (CI)
      0.93-1.03) or after four years (RR 0.97, 95% CI 0.86-1.09). Conclusions:
      Preoperative depression was not associated with lower use of guideline-directed
      medical therapy for secondary prevention after CABG. These findings suggest that
      the observed higher mortality following CABG among depressed patients is not
      explained by inadequate secondary prevention medication.

PMID- 29450169
TI  - Efficacy of non-compliant balloon post-dilation in optimization of contemporary
      stents: A digital stent enhancement study.
AB  - Background: There is no evidence from randomized trials for the benefit of
      routine non-compliant balloon (NCB) post-dilation after stent deployment. Despite
      being the gold standard, intravascular ultrasound is infrequently performed due
      to time and cost constraints and a suitable alternative technology is required
      for routine assessment of stent expansion. The purpose of this study was to
      assess the contribution of NCB post-dilation in optimizing contemporary stents by
      using digital stent enhancement (DSE). Methods: We treated 120 patients with
      stent insertion and assessed the stents with DSE before and after NCB use.
      Optimal expansion was defined as the minimum stent diameter (MSD) >= 90% of the
      nominal stent diameter, an adaptation of the MUSIC and POSTIT trial criteria.
      Stent deployment was performed at 12 atm pressure followed by routine NCB post
      dilation at >= 14 atm. Results: The mean reference diameter on QCA was 2.75 mm
      (SD 0.63) and mean stent diameter was 3.15 mm (SD 0.46). At a mean stent
      deployment pressure of 11.7 atm (SD 2.4), only 21% of stents were optimally
      expanded. After NCB inflation at a mean of 16.9 atm (SD 2.8), MSD increased by
      0.26 mm (SD 0.24), optimal stent expansion increased from 21% to 58% and mean
      stent symmetry ratio increased from 0.83 to 0.87 (p < 0.0001). Conclusions:
      Contemporary stents are sub-optimally expanded in the majority of cases after
      standard deployment compared with nominal sizes. Adjunctive NCB post-dilation
      optimized an additional 37% of stents. DSE analysis can assist in qualitative and
      quantitative stent assessments and can potentially facilitate a selective NCB
      post-dilation strategy to achieve optimal stent expansion.

PMID- 29450170
TI  - Corticosteroids increase intracellular free sodium ion concentration via
      glucocorticoid receptor pathway in cultured neonatal rat cardiomyocytes.
AB  - Background: Glucocorticoids as well as mineralocorticoid have been shown to play
      essential roles in the regulation of electrical and mechanical activities in
      cardiomyocytes. Excess of these hormones is an independent risk factor for
      cardiovascular disease. Intracellular sodium ([Na+]i) kinetics are involved in
      cardiac diseases, including ischemia, heart failure and hypertrophy. However,
      intrinsic mediators that regulate [Na+]i in cardiomyocytes have not been widely
      discussed. Moreover, the quantitative estimation of altered [Na+]i in cultured
      cardiomyocytes and the association between the level of [Na+]i and the severity
      of pathological conditions, such as hypertrophy, have not been precisely
      reported. Methods and results: We herein demonstrate the quantitative estimation
      of [Na+]i in cultured neonatal rat cardiomyocytes following 24 h of treatment
      with corticosterone, aldosterone and dexamethasone. The physiological
      concentration of glucocorticoids increased [Na+]i up to approximately 2.5 mM (an
      almost 1.5-fold increase compared to the control) in a dose-dependent manner;
      this effect was blocked by a glucocorticoid receptor (GR) antagonist but not a
      mineralocorticoid receptor antagonist. Furthermore, glucocorticoids induced
      cardiac hypertrophy, and the hypertrophic gene expression was positively and
      significantly correlated with the level of [Na+]i. Dexamethasone induced the
      upregulation of Na+/Ca2 + exchanger 1 at the mRNA and protein levels.
      Conclusions: The physiological concentration of glucocorticoids increases [Na+]i
      via GR. The dexamethasone-induced upregulation of NCX1 is partly involved in the
      glucocorticoid-induced alteration of [Na+]i in cardiomyocytes. These results
      provide new insight into the mechanisms by which glucocorticoid excess within a
      physiological concentration contributes to the development of cardiac pathology.

PMID- 29450171
TI  - Study of vitamin D deficiency prevalence in acute myocardial infarction.
AB  - Background: Deficiency of 25-hydroxy vitamin D [25(OH)D] is a treatable condition
      that has been associated with coronary artery disease and many of its risk
      factors. A practical time to assess for 25(OH)D deficiency, and to initiate
      treatment, is at the time of an acute myocardial infarction(AMI). The prevalence
      of 25(OH)D deficiency and the characteristics associated with it in patients with
      acute myocardial infarction are unknown. Methods: In this study 25(OH)D was
      assessed in 314 subjects enrolled in a Sri Jayadeva Institute of Cardiovascular
      Science and Research(SJICS&R). Patients enrolled from December 1, 2011 to
      February 28, 2012 had serum samples sent to a centralized laboratory for analysis
      using the ELECYS assay. Normal 25(OH)D levels are >= 30 ng/ml, and patients with
      levels < 30 and > 20 ng/ml were classified as insufficient and those with levels
      <= 20 ng/ml as deficient. Vitamin D and other baseline characteristics were
      analyzed with T-test and chi-squared test. Results: Of the 314 enrolled patents,
      212 (67.5%) were 25(OH)D deficient and 50(16%) were insufficient, for a total of
      83.5% of patients with abnormally low 25(OH)D levels. No significant
      heterogeneity was observed among age or gender sub groups but 25(OH)D deficiency
      was more commonly seen in those with lower socioeconomic status, lower activity
      levels, diabetes, hypercholesterolemia(LDL), hypertriglyceridemia and in smokers.
      Conclusion: Vitamin D deficiency is present in most of the patients with acute
      myocardial infarction and it is associated with many of its risk factors in our
      study.

PMID- 29450172
TI  - Early ambulatory discharge is safe and feasible after transradial coronary
      interventions.
AB  - Background: At present, there are no definite criteria for selecting patients
      eligible for same-day discharge after percutaneous coronary interventions (PCI).
      With rapid ambulation and reduced vascular complication rates, transradial PCI
      have many features that favorably reduce costs and hospital stay. This study
      aimed to demonstrate the possibility of early ambulatory discharge following
      transradial percutaneous coronary interventions. Methods: 254 consecutive
      patients undergoing transradial PCI (elective, urgent, and emergent) at our
      center was observed during hospital stay. Patient demographics, angiographic
      characteristics, post-procedural complications, and timing of these post
      procedural events were recorded. Results: A total of 336 lesions were treated
      among 299 vessels with 277 stents. One hundred fifty-two (45.2%) lesions were
      Type C. There were 26 chronic total occlusions (CTO). One hundred fifty-five
      (61%) patients were discharged on the same day after the procedure. 24
      complications (12.6%) occurred and were divided into three groups according to
      occurrence time. 13 (54.2%) occurred within the first 2 h and 11 (45.8%) occurred
      after the 24-hour period. No complications were observed between the 2nd and 24th
      hours. Conclusions: Same-day discharge with a 2-hour observation period is safe
      and feasible after successful transradial PCI in appropriate patients. Although a
      minor number of complications occurred, these did not occur between the 2nd and
      24th hours. Same-day discharge after successful transradial PCI could be an
      alternative for better utilization of resources.

PMID- 29450173
TI  - Complications of intracoronary abciximab bolus-only versus standard protocol
      during percutaneous coronary intervention in acute coronary syndrome.
AB  - Background: Abciximab reduces major adverse cardiac events in patients with ST
      elevation myocardial infarction undergoing primary percutaneous coronary
      intervention (pPCI). Standard protocol is intravenous abciximab bolus during PCI
      plus abciximab infusion for 12-18 h post pPCI. Intracoronary (IC) abciximab bolus
      administration results in high local drug concentrations and hence it should have
      higher antiplatelet effect. In this study, we assess the short-term efficacy and
      safety of IC compared to IV bolus of abciximab in ACS patients during pPCI.
      Methods: We compared the clinical outcomes between the IC (n = 56) and standard
      protocol (n = 170) group of patients. Primary endpoints included
      bleeding/vascular/ischemic complications and MACE. Results: The two groups were
      similar with respect to baseline characteristics. IC abciximab bolus only reduced
      bleeding complications, with no moderate bleed versus 7.2% in standard protocol
      group (p value 0.04). Ischemic/vascular complications had statistically
      insignificant difference between the two groups. Conclusion: We found no
      significant difference between IC abciximab bolus only and standard abciximab
      therapy in terms of ischemic/vascular complications and MACE. But there was
      higher risk of moderate bleed in standard therapy group. The IC bolus route of
      abciximab may be superior to the intravenous route. Prospective randomized trials
      are warranted to validate these findings.

PMID- 29450174
TI  - Optical coherence tomography characteristics of in-stent restenosis are different
      between first and second generation drug eluting stents.
AB  - Aims: Characterization of neointimal tissue is essential to understand the
      pathophysiology of in-stent restenosis (ISR) after drug eluting stent (DES)
      implantation. Using optical coherence tomography (OCT), we compared the
      morphologic characteristics of ISR between first and second generation DES.
      Methods and Results: OCT was performed in 66 DES-ISR, defined as > 50%
      angiographic diameter stenosis within the stented segment. Patients with ISR of
      first generation sirolimus-eluting stents (SES), paclitaxel eluting stents (PES)
      and second generation zotarolimus-eluting stents (ZES), everolimus-eluting stents
      (EES) and biolimus-eluting stents (BES) were enrolled. Quantitative and
      qualitative ISR tissue analysis was performed at 1-mm intervals along the entire
      stent, and categorised as homogeneous, heterogeneous and neo-atherosclerosis. The
      presence of microvessels and peri-strut low intensity area (PSLIA) was determined
      in all ISR. Neoatherosclerosis was identified by lipid, calcium and thin-cap
      fibro-atheroma (TCFA) like lesions. We compared the two DES generations at both
      early (< 1 year) and late (> 1 year) follow-ups.In second generation DES a
      heterogeneous pattern was prevalent both before and after 1 year (57.1% and 58.6%
      respectively). Neo-atherosclerosis was more common in the early period in first
      generation DES (19.4% vs 11.7%, p < 0.01), but after one year was more prevalent
      in second generation DES (7.0% vs 19.3%, p < 0.01). Similar prevalence of TCFAs
      was observed in both groups in all comparisons. Conclusions: When ISR restenosis
      occurs in second generation DES, the current data suggest a different time course
      and different morphological characteristics from first generation. Future
      prospective studies should evaluate the relationship between ISR morphology, time
      course and clinical events.

PMID- 29450175
TI  - Facilitation of transvenous lead extraction using site-specific delivery of
      electrosurgical energy.
AB  - Introduction: Excimer laser energy is often required to extract chronically
      indwelling pacemaker and defibrillator leads from the vasculature and myocardium.
      This technique can be associated with vascular and right ventricular (RV)
      injuries. We sought to develop a safer, more effective method by applying site
      specific delivery of electrosurgical energy (EE). Methods: Utilizing a
      polyacrylamide gel model to simulate soft tissue density, active and passive
      fixation defibrillator and pacemaker leads were implanted and manually extracted
      with and without EE delivered to the cathode. The amount of force required for
      complete removal was measured using a force transducer. The procedure was then
      repeated in an acute pig model to demonstrate proof of safety. Post mortem gross
      and histologic specimens were collected from the implantation site. Results: In
      the gel model, the force required for extraction, using manual traction in the
      active (83.7 g) and passive (74.6 g) fixation ICD leads, was reduced by 37.8% and
      33.5%, respectively with EE (both p < 0.01). The force required for extraction,
      using manual traction in the active (85.2 g) and passive (71.9 g) fixation
      pacemaker leads, was reduced by 64.4% and 42.6%, respectively with EE (both p <
      0.01). In an acute implantation pig model using an active fixation lead, delivery
      of EE to the cathode (n = 6) reduced the force required to manually extract the
      lead (140 g +/- 32.5 versus 82 g +/- 14.7, p = 0.03). Post mortem analysis of the
      RV displayed formation of an epicardial hemorrhagic lesion that was also present
      after manual traction and EE. There was absence of pericardial effusion,
      perforation, and ventricular arrhythmia. Conclusions: Site-specific delivery of
      EE to areas of exposed metal along the lead decreased the force necessary for
      lead extraction in an in vitro and in vivo model. Further studies are needed to
      evaluate its application in clinical care.

PMID- 29450177
TI  - Isolated left coronary ostial occlusion detected by multislice computed
      tomography.

PMID- 29450176
TI  - Echocardiographic elastic properties of ascending aorta and their relationship
      with exercise capacity in patients with non-ischemic dilated cardiomyopathy.
AB  - Background: : Aortic stiffness, an independent predictor of mortality and
      cardiovascular events, is common among patients affected by non-ischemic dilated
      cardiomyopathy (NIDC) and heart failure (HF). Methods: : A total of 55 patients
      with diagnosis of NIDC (aged 60 +/- 11 years, mean ejection fraction (EF) 35.2%
      +/- 7.7%) admitted consecutively to our department for mild to moderate HF (NYHA
      class II-III) underwent an echocardiographic study and cardiopulmonary exercise
      test (CPX). We evaluated elastic properties of ascending aorta, i.e. aortic
      stiffness and aortic distensibility (mm Hg- 1), derived from ascending aorta
      systolic and diastolic diameter (mm/m2) measured 3 cm above the valvular plane
      through 2D-guided M-mode echocardiography. Results: : Mean aortic stiffness was
      15.63 +/- 14.53 and aortic distensibility was 2.61 +/- 2.39 mm Hg- 1. Collected
      parameters at CPX were peak oxygen consumption (pVO2) (ml/kg/min), anaerobic
      threshold (AT) and the slope of the relation between minute ventilation (VE) and
      carbon dioxide production (VCO2). Mean pVO2 was 15.4 +/- 3.9 ml/kg/min, VE/VCO2
      ratio at AT was 36.1 +/- 6.1. Functional capacity measured through peak VO2 was
      found to be directly correlated with aortic distensibility (r = 0.47, p = -
      0.0002) and negatively correlated to aortic stiffness index (r = - 0.51, p = -
      0.0001). These results were the same at multivariate analysis, corrected by age,
      hypertension, diabetes mellitus and ejection fraction (respectively r = 0.27, p =
      0.008 and r = - 1.75, p = 0.0002). Conclusions: : HF patients due to NIDC elastic
      properties of ascending aorta, evaluated by echocardiography, are correlated with
      a reduced functional capacity.

PMID- 29450178
TI  - "Arterial circle of Vieussens" - An important intercoronary collateral.

PMID- 29450179
TI  - Kinking of the aorta with calcified aortic valve stenosis: A case report.
AB  - Congenital kinking of the aorta is an uncommon anomaly consisting of elongation
      of the aortic arch with kinking at the level of the ductal ligament. Herein we
      report a case of congenital kinking of the aorta with calcified aortic valve
      stenosis. The combination of a kinked aorta with severe calcified valve stenosis
      is very unusual.

PMID- 29450180
TI  - Predictors of in-hospital mortality in patients with acute myocardial infarction
      complicated by cardiogenic shock in the contemporary era of primary percutaneous
      coronary intervention.

PMID- 29450181
TI  - Surgical ablation of atrial fibrillation.
AB  - Surgical ablation of atrial fibrillation (AF) is currently performed in many
      major hospitals throughout the world. This paper reviews the development of
      surgical procedures for AF ablation. It is hoped that the paper can provide a
      foundation for those involved with ablation of AF to improve patient care. AF is
      triggered by a rapidly firing focus and could be treated with a localized
      ablation procedure. A large body of literature has confirmed the safety and
      efficacy of surgical ablation of AF. New ablation technologies have simplified
      the surgical treatment of AF and expanded the indications. Generally, more
      extensive lesion sets have had better long-term outcomes. Despite the tremendous
      progress that has been made in the development of surgical ablation of AF, many
      questions remain unanswered. It is anticipated that well designed clinical trials
      will continue to provide solid evidence to help formulate practice guidelines in
      the future.

PMID- 29450182
TI  - Predictive value of neutrophil to lymphocyte ratio for the presence of coronary
      artery ectasia in patients with aortic aneurysms.
AB  - Background: Both aortic aneurysms and coronary artery ectasia (CAE) frequently
      coexist and are associated with more pronounced inflammation. Neutrophil to
      lymphocyte ratio (NL ratio) is widely used as a marker of inflammation. However,
      relation between CAE and NL ratio in patients with aortic aneurysms is not fully
      understood. This study was undertaken to assess relation between CAE and NL ratio
      in patients with aortic aneurysms. Methods: This study consisted of 93
      consecutive patients with aortic aneurysms (AA group) and 79 patients without
      aortic aneurysms who had angiographically normal coronary arteries as the control
      group. Moreover, patients with aortic aneurysms were classified into two groups
      based on the presence of CAE; CAE (+) group (n = 44) and CAE (-) group (n = 49).
      We compared blood chemical parameters in both groups. Results: In the AA group,
      44 patients (47.3%) had CAE. The AA group had a significantly higher NL ratio
      than the control group (2.93 +/- 1.43 vs. 2.45 +/- 1.05, p = 0.027). Furthermore,
      the CAE (+) group had a significantly higher NL ratio than the CAE (-) group
      (3.39 +/- 1.67 vs. 2.52 +/- 1.04, p < 0.01). Multivariate logistic regression
      analysis revealed that the high NL ratio was an independent predictor for CAE in
      patients with aortic aneurysms (odds ratio 1.76, 95% confidence interval 1.24
      2.69, p = 0.001). Conclusions: Patients with aortic aneurysms had a significantly
      higher NL ratio than those without aortic aneurysms. Furthermore, the NL ratio
      might predict the presence of CAE in patients with aortic aneurysms.

PMID- 29450183
TI  - Trends in percutaneous coronary intervention and angiography in Ireland, 2004
      2011: Implications for Ireland and Europe.
AB  - Background/objectives: To study temporal trends in crude and age standardised
      rates of cardiac catheterisation and percutaneous coronary intervention (PCI) in
      Ireland, 2004-2011. Methods: Two data sources were used: a) a survey of publicly
      and privately funded hospitals with cardiac catheter laboratories to obtain the
      annual number of procedures performed and b) anonymised data from the Hospital In
      Patient Enquiry (HIPE) for angiography and PCI in acute publicly funded
      hospitals; age standardised rates were calculated to study trends over time.
      Results: From 2004 to 2011 the crude rate of angiography and PCI increased by
      47.8% and 35.9% respectively, with rates of 6689 and 1825 per million population
      in 2011. Following age standardisation, however, PCI activity showed a non
      significant decrease over time. The PCI to angiography ratio decreased from 30%
      to 27% and PCI was performed predominantly for stable coronary heart disease
      (54%) in 2011. Conclusion: Angiography and PCI rates have increased in Ireland
      but PCI crude and age adjusted rates show divergent trends. While Ireland differs
      from USA and UK, with a higher proportion of PCI being performed for stable CHD
      in recent years, little systematic surveillance of cardiological interventions
      within Europe is available to benchmark improvements in Ireland.

PMID- 29450184
TI  - Absence of significant aortic regurgitation seven years after closure of patent
      foramen ovale.
AB  - Background: It has been suggested that there is an increase in aortic
      regurgitation (AR) in the short and medium term after percutaneous closure of
      patent foramen ovale (PFO). The aim of this study is to determine the long-term
      effect of percutaneous closure of PFO on the prevalence of AR. Methods: Patients
      with cryptogenic stroke or transient ischemic attack who had undergone
      percutaneous closure of PFO more than five years before the study were invited to
      an echocardiographic examination. Results: Out of 83 invited patients, 64
      accepted the invitation and were examined with echocardiography. Mild AR was
      found in one patient (2%), but this was already evident in the patient's
      echocardiographic result before PFO closure. Trace AR was detected in 11 patients
      (17%). No case of moderate or severe AR was detected. Patients with AR were more
      often hypertensive (six out of 12 patients with AR, compared to nine of the 52
      without AR, p = 0.025), and the indexed sinus of Valsalva was larger in patients
      with AR (18.6 mm/m2, SD 1.6, as compared to 17.3 mm/m2, SD 1.6, p = 0.02).
      Conclusion: In this long-term study with a minimum follow-up of 5.6 years and a
      mean of 7.1 years, we found negligible levels of AR. Where present, AR was
      associated with hypertension and mild dilatation of the aortic root, but there
      was no indication that device closure per se increased the risk of developing AR.

PMID- 29450185
TI  - The predictive role of electrocardiographic abnormalities in ischemic stroke
      patients with intravenous thrombolysis.
AB  - Background/Objectives: The association between electrocardiographic abnormalities
      and the outcomes in acute ischemic stroke patients after intravenous thrombolysis
      remains unclear. We sought to assess the predictive value of electrocardiographic
      abnormalities in stroke patients after thrombolysis. Methods: Consecutive acute
      stroke patients with thrombolysis from Feb 2008 to Jun 2013 were included.
      Electrocardiographic abnormalities during hospitalization were retrospectively
      reviewed. Outcomes were 90-day modified Rankin's Score. Multivariate logistic
      regression was used to analyze the association of electrocardiographic
      abnormalities with 90-day outcome. Results: From Feb 2008 to Jun 2013, 95 acute
      stroke patients (median age of 67 and 64.2% male) with electrocardiographic
      before/after thrombolysis and 90 day modified Rankin's Score were recruited in
      our study. Increased age (p = 0.027), higher baseline National Institutes of
      Health Stroke Scale (p < 0.001) and T-wave changes (p = 0.030) were significantly
      associated with worse functional outcome. T-wave changes (odds ratio 5.54, 95%
      confidence interval 1.37-22.37, p = 0.016) were independently associated with
      unfavorable outcome. Conclusions: T-wave changes can be useful markers to predict
      the outcome in stroke patients after thrombolysis.

PMID- 29450187
TI  - Factors associated with longer delays in reperfusion in ST-segment elevation
      myocardial infarction.
AB  - Background/objectives: The goal of this paper is to identify the predictors of
      delay in total ischemia time that would be the focus of improvement efforts in
      patients with ST-segment elevation myocardial infarction. Methods: Data was
      collected retrospectively through the patient's clinical records and by direct
      telephone interview.Total ischemic time was categorized in two classes according
      to the elapsed time since symptom presentation until restored flow, less than 6 h
      and 6 h or less. Logistic regression analysis was applied to evaluate the
      relationship between total ischemic time and a set of variables. Discrimination
      ability of the model was also assessed, as well as sensitivity and specificity,
      through ROC curves. Results: Data from 128 patients, 74.22% males and 25.78%
      females, were analyzed. The average age was approximately 62 years (+/- 13.6).Six
      variables associated with total ischemia were selected in the final model: the
      patient age, the level of pain intensity, the region of origin, the socioeconomic
      status, the activity that the patient was performing at the time of symptoms
      onset, and the fact that the patient has been transferred from another hospital.
      Conclusion: The identification of variables associated with the total ischemia
      time allows the recognition of patients with possibility of worse prognosis, for
      which should be directed educational efforts and also the identification of
      variables that can be modified to optimize the therapy.

PMID- 29450188
TI  - Improved survival rate after myocardial infarction using an inducible cholesterol
      efflux (iCE) peptide: FAMP.
AB  - Background: There have been no previous reports that apolipoprotein (apo) A-I
      mimetic peptide improves survival rate after myocardial infarction (MI). Method
      and results: Male C57Bl/6J mice were subjected to left coronary artery permanent
      ligation as a model of MI. We synthesized a novel 24-amino acid apoA-I mimetic
      peptide-type5 (FAMP5), which potently removes cholesterol via specific ATP
      binding cassette transporter A1 (ABCA1). FAMP5 was associated with a
      significantly improved survival rate by protecting against cardiac rupture
      compared to the control. mRNA levels for eNOS, Gata-4, CTGF and ANP were
      significantly increased in the hearts of the FAMP5-treated group, while that for
      MCP-1 decreased. Conclusion: This is the first report that high-density
      lipoprotein (HDL) therapy with FAMP5 improved the survival rate after MI.

PMID- 29450186
TI  - Regional variations in baseline characteristics of cardiac rhythm device
      recipients: The PANORAMA observational cohort study.
AB  - Background: The PANORAMA study was designed to collect concurrent data on
      subjects from different worldwide regions implanted with CRM devices. Methods: In
      this prospective, multi-center study, we analyzed baseline data on 8586 subjects
      implanted with CRM devices with no additional selection criteria (66% pacemaker
      (IPG), 16% implantable cardiac defibrillators (ICD), 17% cardiac
      resynchronization therapy (CRT) and < 1% Internal Loop Recorder) from 156
      hospitals across 6 geographical regions between 2005 and 2011. Results:
      Regardless of the device implanted, subjects from the Middle East and India often
      had more diabetes than other regions. Eastern and Western Europe had higher rates
      of atrial fibrillation reported, and men were more likely to smoke than women
      (46% vs 11%, p < 0.001). Within the CRT cohort there was significant variation in
      the proportion of males receiving a device, ranging from 55% in India to 83% in
      Eastern Europe. Conclusions: We provide comprehensive descriptive data on
      patients receiving CRM devices from a range of geographies that are not typically
      reported in literature. We found significant variations in clinical
      characteristics and implant practices. Long term follow-up data will help
      evaluate if these variations require adjustments to outcome expectations.

PMID- 29450189
TI  - Effects of transcatheter aortic valve implantation on ascending aorta wall
      elastic properties: Tissue Doppler imaging and strain Doppler echocardiography
      study.
AB  - Background: Aortic elastic properties are determinants of left ventricular
      function by means of ventriculo-arterial coupling and indicators of
      cardiovascular risk. Aortic valve stenosis surgical replacement temporary reduces
      aortic function damaging vasa vasorum, while transcatheter aortic valve
      implantation (TAVI) does not influence it in the short term. We studied aortic
      distensibility, stiffness, M-mode strain and tissue strain after 6 and 12 months
      from TAVI. Methods: We enrolled 15 patients with symptomatic severe aortic
      stenosis who underwent CoreValve prosthesis (Medtronic, Minneapolis, MN)
      implantation. Everyone had blood pressure measurement and echocardiography
      registration before TAVI and after 6 and 12 months. Results: After TAVI NYHA
      class (p = 0.016), peak and mean aortic valve gradients (p < 0.001 for both)
      improved. Aortic distensibility increased (p = 0.032 in the first 6 months, p =
      0.005 in the second 6 months, and p = 0.003 from baseline to 12 months), as well
      as stiffness decreased (p = 0.034; 0.090; 0.001), M-mode strain and tissue strain
      ameliorated (p = 0.041; 0.004; 0.004; and p = 0.013; 0.002; 0.001, respectively),
      tissue Doppler imaging improved (S' wave: p = 0.289; 0.347; 0.018. E' wave: p =
      0.018; 0.113; 0.007. A' wave: p = 0.002; 0.532; 0.001). Moreover, some left
      ventricular parameters improved at 6 months, such as ejection fraction (from 49
      +/- 16 to 57 +/- 11%; p = 0.044) and diastolic interventricular septum thickness
      (from 14 +/- 2 to 12 +/- 2 mm; p = 0.010). Even systolic pulmonary artery
      pressure (p = 0.019) and left diastolic dysfunction grade ameliorated (p =
      0.042). Conclusions: For the first time we demonstrated that aortic elastic
      properties improve at 6 and 12 months after TAVI, thus influencing ventriculo
      arterial coupling and ameliorating left ventricular function.

PMID- 29450190
TI  - Left atrial emptying fraction predicts limited exercise performance in heart
      failure patients.
AB  - Aim: We aimed in this study to assess the role of left atrial (LA), in addition
      to left ventricular (LV) indices, in predicting exercise capacity in patients
      with heart failure (HF). Methods: This study included 88 consecutive patients (60
      +/- 10 years) with stable HF. LV end-diastolic and end-systolic dimensions,
      ejection fraction (EF), mitral and tricuspid annulus peak systolic excursion
      (MAPSE and TAPSE), myocardial velocities (s', e' and a'), LA dimensions, LA
      volume and LA emptying fraction were measured. A 6-min walking test (6-MWT)
      distance was performed on the same day of the echocardiographic examination.
      Results: Patients with limited exercise performance (<= 300 m) were older (p =
      0.01), had higher NYHA functional class (p = 0.004), higher LV mass index (p =
      0.003), larger LA (p = 0.002), lower LV EF (p = 0.009), larger LV end-systolic
      dimension (p = 0.007), higher E/A ratio (p = 0.03), reduced septal MAPSE (p <
      0.001), larger LA end-systolic volume (p = 0.03), larger LA end-diastolic volume
      (p = 0.005) and lower LA emptying fraction (p < 0.001) compared with good
      performance patients. In multivariate analysis, only the LA emptying fraction
      [0.944 (0.898-0.993), p = 0.025] independently predicted poor exercise
      performance. An LA emptying fraction < 60% was 68% sensitive and 73% specific
      (AUC 0.73, p < 0.001) in predicting poor exercise performance. Conclusion: In
      heart failure patients, the impaired LA emptying function is the best predictor
      of poor exercise capacity. This finding highlights the need for routine LA size
      and function monitoring for better optimization of medical therapy in HF.

PMID- 29450191
TI  - Dobutamine stress testing induced transient cardiomyopathy: A systematic review.

PMID- 29450192
TI  - The Adhesion G-Protein-Coupled Receptor, GPR56/ADGRG1, Inhibits Cell
      Extracellular Matrix Signaling to Prevent Metastatic Melanoma Growth.
AB  - Metastatic growth is considered a rate-limiting step in cancer progression, and
      upregulation of extracellular matrix (ECM) deposition and cell-ECM signaling are
      major drivers of this process. Mechanisms to reverse ECM upregulation in cancer
      could potentially facilitate its prevention and treatment but they are poorly
      understood. We previously reported that the adhesion G-protein-coupled receptor
      GPR56/ADGRG1 is downregulated in melanoma metastases. Its re-expression inhibited
      melanoma growth and metastasis and reduced the deposition of fibronectin, a major
      ECM component. We hypothesize that its effect on fibronectin deposition
      contributes to its inhibitory role on metastatic growth. To test this, we
      investigated the function of GPR56 on cell-fibronectin adhesion and its
      relationship with metastatic growth in melanoma. Our results reveal that GPR56
      inhibits melanoma metastatic growth by impeding the expansion of micrometastases
      to macrometastases. Meanwhile, we present evidence that GPR56 inhibits
      fibronectin deposition and its downstream signaling, such as phosphorylation of
      focal adhesion kinase (FAK), during this process. Administration of the FAK
      inhibitor Y15 perturbed the proliferation of melanoma metastases, supporting a
      causative link between the cell adhesion defect induced by GPR56 and its
      inhibition of metastatic growth. Taken together, our results suggest that GPR56
      in melanoma metastases inhibits ECM accumulation and adhesion, which contributes
      to its negative effects on metastatic growth.

PMID- 29450193
TI  - A Method for Quantification of Epithelium Colonization Capacity by Pathogenic
      Bacteria.
AB  - Most bacterial infections initiate at the mucosal epithelium lining the
      gastrointestinal, respiratory, and urogenital tracts. At these sites, bacterial
      pathogens must adhere and increase in numbers to effectively breach the outer
      barrier and invade the host. If the bacterium succeeds in reaching the
      bloodstream, effective dissemination again requires that bacteria in the blood,
      reestablish contact to distant endothelium sites and form secondary site foci.
      The infectious potential of bacteria is therefore closely linked to their ability
      to adhere to, colonize, and invade epithelial and endothelial surfaces.
      Measurement of bacterial adhesion to epithelial cells is therefore standard
      procedure in studies of bacterial virulence. Traditionally, such measurements
      have been conducted with microtiter plate cell cultures to which bacteria are
      added, followed by washing procedures and final quantification of retained
      bacteria by agar plating. This approach is fast and straightforward, but yields
      only a rough estimate of the adhesive properties of the bacteria upon contact,
      and little information on the ability of the bacterium to colonize these surfaces
      under relevant physiological conditions. Here, we present a method in which
      epithelia/endothelia are simulated by flow chamber-grown human cell layers, and
      infection is induced by seeding of pathogenic bacteria on these surfaces under
      conditions that simulate the physiological microenvironment. Quantification of
      bacterial adhesion and colonization of the cell layers is then performed by in
      situ time-lapse fluorescence microscopy and automatic detection of bacterial
      surface coverage. The method is demonstrated in three different infection models,
      simulating Staphylococcus aureus endothelial infection and Escherichia coli
      intestinal- and uroepithelial infection. The approach yields valuable information
      on the fitness of the bacterium to successfully adhere to and colonize epithelial
      surfaces and can be used to evaluate the influence of specific virulence genes,
      growth conditions, and antimicrobial treatment on this process.

PMID- 29450194
TI  - Avoiding Arterial Hypotension in Preterm Neonates (AHIP)-A Single Center
      Randomised Controlled Study Investigating Simultaneous Near Infrared Spectroscopy
      Measurements of Cerebral and Peripheral Regional Tissue Oxygenation and Dedicated
      Interventions.
AB  - Introduction: Up to 50% of preterm infants admitted to intensive care units
      require cardiocirculatory support. The aim of the present study was to assess
      whether simultaneous monitoring of cerebral tissue oxygenation index (cTOI) and
      peripheral tissue oxygenation index (pTOI) using near-infrared spectroscopy
      (NIRS) in combination with dedicated intervention guidelines may help avoiding
      arterial hypotension and catecholamine administration in preterm neonates. Study
      design: Preterm neonates <37 weeks of gestation were included in a single center
      randomized controlled study. Blood pressure was measured non-invasively or
      invasively. In the NIRS group, simultaneous cTOI and pTOI monitoring was used
      starting within 6 h after birth for 24 h to calculate changes in cTOI/pTOI ratio
      over time. Depending on these changes, interventions including echocardiography,
      administration of volume or patent ductus arteriosus treatment were performed. In
      the control group, only routine monitoring and treatment were performed and NIRS
      signals were not visible. The primary outcome was burden of hypotension within 48
      h after initiation of NIRS monitoring. Results: 49 preterm neonates were included
      in each group: NIRS group 33.1 (32.0-34.0) (median: 25-75 centile) weeks of
      gestation and control group 33.4 (32.3-34.3) weeks of gestation. In the NIRS
      group, echocardiography was performed in 17 preterm neonates due to NIRS
      measurements, whereby six neonates received further treatment. Percentage of
      neonates with any hypotensive episode during the 48-h observational period was
      32.6% in the NIRS group and 44.9% in the control group (p = 0.214). Burden of
      hypotension (i.e., %mmHg of mean arterial pressure < gestational age) was 0.0
      (0.0-2.1) mmHg h in the NIRS group and 0.4 (0.0-3.3) mmHg h in the control group
      (p = 0.313), with observed burden of hypotension being low in both groups. No
      severe adverse reactions were observed. Conclusion: In preterm neonates using
      simultaneous peripheral and cerebral NIRS measurements for early detection of
      centralization followed by predefined interventions led to a non-significant
      reduction in burden of arterial hypotension. Clinical Trial Registration:
      www.ClinicalTrials.gov, identifier: NCT01910467.

PMID- 29450195
TI  - Insecticide-Treated Nets Utilization and Associated Factors among under-5 Years
      Old Children in Mirab-Abaya District, Gamo-Gofa Zone, Ethiopia.
AB  - Background: Malaria can be prevented using cost-effective interventions. It can
      be prevented at large via the use of insecticide-treated mosquito nets (ITNs).
      The use of ITNs decreases malaria mortality rates by 55% in under-5 years old
      children in Africa, Ethiopia, realizing the effectiveness, scaling up
      distribution and utilization of ITNs to cover 100% of children less than 5 years
      of age. However, little is known about ITNs utilization and factors associated
      with the utilization in under-5 years old children in the study area yet. The
      purpose of this study was to assess the level and associated factors of ITNs
      utilization in under-5 years old children among households with under-5 years old
      children of Mirab Abaya District, Gamo Gofa Zone, Ethiopia. Methods: A community
      based cross-sectional study was conducted during August-September, 2016. Six
      study Kebeles were identified by simple random sampling technique and 398
      households with at least one under-5 years old children were selected by random
      sampling technique using computer generated random numbers from health post
      family folders. Structured, interviewer questionnaire was administered to mothers
      or care givers of the children. Data were entered to Epi Info Version 3.5 and
      analyzed in SPSS version 21 statistical software. Bivariate and multivariate
      logistic regression analysis was done. P-value <0.05 and odds ratio with 95%
      confidence interval were used for the determination of associations between
      dependent and predictor variables. Results were presented in narrations, tables,
      and graph. Result: Among 398 under-5 years old children assessed, the majority,
      362 (91.0%) of them had access to ITN, but only 137 (37.2%) of the child had ITNs
      utilization during the previous night prior to the survey. Households with age of
      mothers or caretakers 31-44 years, AOR = 0.03, 95% CI (0.01-0.07) and >=45 years
      of age; AOR = 0.05, 95% CI (0.01-0.58); households with family size <=5 members,
      AOR = 11.23, 95% CI (4.31-29.24); and households with sleeping space >=2, AOR =
      13.59, 95% CI (4.40-41.93) were found to be significantly associated with under-5
      years old children ITNs utilization. Conclusion: Even though, a significant
      proportions of under-5 years old children had access to ITN, only one-third of
      the participant child utilized it properly.

PMID- 29450196
TI  - Recruitment and Lessons Learned from a Community-Based Intervention Program: The
      Learning Families Project in Hong Kong.
AB  - Background: Recruitment is central to any research project, and recruitment
      itself should be well documented and researched. We describe our recruitment
      efforts for a community-based research project-entitled the Learning Families
      Project-conducted in Hong Kong. Methods: In collaboration with community
      stakeholders, residents from a public housing estate were recruited to
      participate in family programs aimed at enhancing family well-being. Various
      recruitment strategies were employed including the distribution of 19,200
      leaflets, 688 posters, a banner, a kick-off ceremony, 10 promotion activities,
      1,000 direct calls, word of mouth, 51 mobile counters, and 10 door-to-door
      visits. Drawing on field notes, research logs, short questionnaires, and focus
      group conducted with our community partners and residents, we describe and
      discuss our recruitment strategies, challenges, and lessons learned. Results:
      Over a 9-month period, 980 participants were recruited and participated in our
      study, exceeding our recruitment goal (860 participants). Several observations
      were made including active recruitment strategies (i.e., door-to-door and mobile
      counter) being more effective than passive strategies (i.e., posters and
      leaflets); the importance of raising project awareness to facilitate recruitment;
      and the challenges encountered (i.e., burn-out and loss of motivation of staff,
      decreased community capacity in collaborating in research projects). Conclusion:
      The lessons learned include the importance of engaging Chinese communities,
      utilizing a positive outreach approach, and setting realistic expectations.
      Although similar recruitment strategies have been reported the West, a number of
      cultural differences should be taken into account when working with Chinese
      population. Further research is needed to examine the effectiveness of tailoring
      recruitment strategies to various populations.

PMID- 29450197
TI  - Platelet Counts in Insoluble Platelet-Rich Fibrin Clots: A Direct Method for
      Accurate Determination.
AB  - Platelet-rich fibrin (PRF) clots have been used in regenerative dentistry most
      often, with the assumption that growth factor levels are concentrated in
      proportion to the platelet concentration. Platelet counts in PRF are generally
      determined indirectly by platelet counting in other liquid fractions. This study
      shows a method for direct estimation of platelet counts in PRF. To validate this
      method by determination of the recovery rate, whole-blood samples were obtained
      with an anticoagulant from healthy donors, and platelet-rich plasma (PRP)
      fractions were clotted with CaCl2 by centrifugation and digested with tissue
      plasminogen activator. Platelet counts were estimated before clotting and after
      digestion using an automatic hemocytometer. The method was then tested on PRF
      clots. The quality of platelets was examined by scanning electron microscopy and
      flow cytometry. In PRP-derived fibrin matrices, the recovery rate of platelets
      and white blood cells was 91.6 and 74.6%, respectively, after 24 h of digestion.
      In PRF clots associated with small and large red thrombi, platelet counts were
      92.6 and 67.2% of the respective total platelet counts. These findings suggest
      that our direct method is sufficient for estimating the number of platelets
      trapped in an insoluble fibrin matrix and for determining that platelets are
      distributed in PRF clots and red thrombi roughly in proportion to their
      individual volumes. Therefore, we propose this direct digestion method for more
      accurate estimation of platelet counts in most types of platelet-enriched fibrin
      matrix.

PMID- 29450198
TI  - Parvovirus B19: What Is the Relevance in Transfusion Medicine?
AB  - Parvovirus B19 (B19V) has been discovered in 1975. The association with a disease
      was unclear in the first time after the discovery of B19V, but meanwhile, the
      usually droplet transmitted B19V is known as the infectious agent of the "fifth
      disease," a rather harmless children's illness. But B19V infects erythrocyte
      progenitor cells and thus, acute B19V infection in patients with a high
      erythrocyte turnover may lead to a life-threatening aplastic crisis, and acutely
      infected pregnant women can transmit B19V to their unborn child, resulting in a
      hydrops fetalis and fetal death. However, in many adults, B19V infection goes
      unnoticed and thus many blood donors donate blood despite the infection. The B19V
      infection does not impair the blood cell counts in healthy blood donors, but
      after the acute infection with extremely high DNA concentrations exceeding 1010
      IU B19V DNA/ml plasma is resolved, B19V DNA persists in the plasma of blood
      donors at low levels for several years. That way, many consecutive donations that
      contain B19V DNA can be taken from a single donor, but the majority of blood
      products from donors with detectable B19V DNA seem not to be infectious for the
      recipients from several reasons: first, many recipients had undergone a B19V
      infection in the past and have formed protective antibodies. Second, B19V DNA
      concentration in the blood product is often too low to infect the recipient.
      Third, after the acute infection, the presence of B19V DNA in the donor is
      accompanied by presumably neutralizing antibodies which are protective also for
      the recipient of his blood products. Thus, transfusion-transmitted (TT-) B19V
      infections are very rarely reported. Moreover, in most blood donors, B19V DNA
      concentration is below 1,000 IU/ml plasma, and no TT-B19V infections have been
      found by such low-viremic donations. Cutoff for an assay for B19V DNA blood donor
      screening should, therefore, be approximately 1,000 IU/ml plasma, if a general
      screening of blood donors for single donation blood components is considered at
      all: for the overwhelming majority of transfusion recipients, B19V infection is
      not relevant as well as for the blood donors. B19V DNA screening of vulnerable
      patients after transfusion seems to be a more reasonable approach than general
      blood donor screening.

PMID- 29450199
TI  - Transfusion-Transmitted Hepatitis E: NAT Screening of Blood Donations and
      Infectious Dose.
AB  - The risk and importance of transfusion-transmitted hepatitis E virus (TT-HEV)
      infections by contaminated blood products is currently a controversial discussed
      topic in transfusion medicine. The infectious dose, in particular, remains an
      unknown quantity. In the present study, we illuminate and review this aspect seen
      from the viewpoint of a blood donation service with more than 2 years of
      experience in routine HEV blood donor screening. We systematically review the
      actual status of presently known cases of TT-HEV infections and available routine
      NAT-screening assays. The review of the literature revealed a significant
      variation regarding the infectious dose causing hepatitis E. We also present the
      outcome of six cases confronted with HEV-contaminated blood products, identified
      by routine HEV RNA screening of minipools using the highly sensitive RealStar HEV
      RT-PCR Kit (95% LOD: 4.7 IU/mL). Finally, the distribution of viral RNA in
      different blood components [plasma, red blood cell concentrate (RBC), platelet
      concentrates (PC)] was quantified using the first WHO international standard for
      HEV RNA for NAT-based assays. None of the six patients receiving an HEV
      contaminated blood product from five different donors (donor 1: RBC, donor 2-5:
      APC) developed an acute hepatitis E infection, most likely due to low viral load
      in donor plasma (<100 IU/mL). Of note, the distribution of viral RNA in blood
      components depends on the plasma content of the component; nonetheless, HEV RNA
      could be detected in RBCs even when low viral plasma loads of 100-1,000 IU/mL are
      present. Comprehensive retrospective studies of TT-HEV infection offered further
      insights into the infectivity of HEV RNA-positive blood products. Minipool HEV
      NAT screening (96 samples) of blood donations should be adequate as a routine
      screening assay to identify high viremic donors and will cover at least a large
      part of viremic phases.

PMID- 29450200
TI  - Nutritional Compositions and Phytochemical Properties of the Edible Flowers from
      Selected Zingiberaceae Found in Thailand.
AB  - The nutritional compositions and phytochemical properties of eight edible flowers
      of the ginger family (Zingiberaceae) commonly found in Thailand are reported
      herein. The plant genera investigated were Zingiber (Ginger, Phlai Dam, Krathue),
      Hedychium (two morphological filament forms), Curcuma (Ao), Etlingera (Torch
      ginger), Amomum (Chi Kuk), and Alpinia (Galangal), which are eaten fresh or
      cooked as ingredients in the preparation of many Thai dishes. The proximate
      compositions (moisture, ash, fiber, protein, fat, and carbohydrate contents)
      varied among the different genera. The plants sampled were generally low in fat
      content (<1%), which contributed as little as 30% of the total caloric energy.
      Edible plant parts contained substantially high amounts of potassium (max. 737.21
      mg/100 g), calcium (max. 140.15 mg/100 g), and iron (~0.32 mg/100 g). Among the
      tested samples, torch ginger had the highest vitamin C content (1.05 mg/100 g),
      total phenolic and total flavonoid contents, as well as 2,2-diphenyl-1
      picrylhydrazyl activity. On the other hand, the 2,2'-azino-bis (3
      ethylbenzothiazoline-6-sulfonic acid) assay suggested that Hedychium species
      possessed the highest antioxidant activity (~5.38 mg TEAC/g extract). Our results
      prove that edible plants of the Zingiberaceae family found in Thailand are rich
      sources of potentially important nutrients.

PMID- 29450201
TI  - Supporting patients self-managing respiratory health: a qualitative study on the
      impact of the Breathe Easy voluntary group network.
AB  - Self-management strategies are designed to improve lung and respiratory health
      through structured self-management plans with regular practitioner reviews.
      Strategies have not, however, focused upon how patient support groups and
      advocacy networks can help with the management of these conditions; therefore, it
      is unknown what impact they may have on patient self-management. A qualitative
      study was designed to help understand what impact the British Lung Foundation's
      Breathe Easy (BE) groups have on patients managing their lung and respiratory
      conditions. A semistructured telephone interview schedule was developed to study
      the network. Topics covered included: perceptions about the BE groups; current
      referrals systems and integration pathways; benefits of attending the BE groups;
      and integration of the BE groups into the respiratory pathway. Key themes
      explored included: shared patient experience and peer support; patient self
      management and self-education; attendance of healthcare professionals; and the
      impact of integrating BE groups into the respiratory pathway. BE networks were
      shown to support self-care initiatives for people attending the groups, and
      members expressed a social and educational benefit. BE networks were working with
      the local National Health Service to become an integral part of the respiratory
      pathway, yet there was evidence of resistance from the health service in
      incorporating the networks.

PMID- 29450202
TI  - The European Respiratory Society course on acute respiratory pandemics: how to
      plan for and manage them.
AB  - Learn about the @ERStalk course on acute respiratory pandemics
      http://ow.ly/XGe430i7743.

PMID- 29450203
TI  - Real-life experience of ceritinib in crizotinib-pretreated ALK+ advanced non
      small cell lung cancer patients.
AB  - Here we report our experience of ceritinib in crizotinib-pretreated patients with
      anaplastic lymphoma kinase (ALK) positive (ALK+) non-small cell lung cancer
      (NSCLC) in a French temporary authorisation for use (TAU) study. The French TAU
      study included crizotinib-pretreated patients with advanced ALK+ or ROS proto
      oncogene 1 positive (ROS1+) tumours. Patients received oral ceritinib (750 mg.day
      1 as a starting dose) and best tumour response (as evaluated by the investigator)
      and safety were reported every 3 months. A total of 242 TAUs were granted from
      March 12, 2013 to August 05, 2015. Of the 242 patients, 228 had ALK+ NSCLC and 13
      had ROS1+ NSCLC. The median age of ALK+ patients (n=214) was 58.5 years, 51.9%
      were female, 70.8% had an Eastern Cooperative Oncology Group (ECOG) performance
      status (PS) of 0-1 and 50.0% had brain metastases. Of the 149 efficacy evaluable
      ALK+ NSCLC patients, 5.4% had a complete response (CR), 47.0% had a partial
      response (PR) and 22.8% had stable disease (SD). At September 05, 2015, the
      median duration of ceritinib treatment (n=182) was 3.9 months but 5.5 months for
      patients (n=71) with a follow-up of >=12 months. Higher objective response rate
      (ORR) was observed for patients with ECOG PS 0 to 1 (55.0% versus 42.4%) and
      those receiving prior crizotinib for >5 months (51.6% versus 36.1%). Treatment
      related adverse events (AEs) were reported in 118 of 208 patients (56.7%), the
      most common being diarrhoea (22.1%) and hepatic toxicity (19.7%). Ceritinib (750
      mg.day-1) demonstrated efficacy similar efficacy to ASCEND-1, ASCEND-2 and phase
      3 ASCEND-5 trials with manageable safety in crizotinib-pretreated patients with
      ALK+ NSCLC.

PMID- 29450205
TI  - Revision Surgery After Cartilage Repair: Data From the German Cartilage Registry
      (KnorpelRegister DGOU).
AB  - Background: Various operative strategies have been introduced to restore the
      integrity of articular cartilage when injured. The frequency of revision surgery
      after cartilage regenerative surgery remains incompletely understood.
      Purpose/Hypothesis: The purpose of this study was to identify the reasons for
      revision surgery after cartilage regenerative surgery of the knee. We
      hypothesized that in a large patient cohort, revision rates would differ from
      those in the current literature. Study Design: Case-control study; Level of
      evidence, 3. Methods: A total of 2659 complete data sets from the German
      Cartilage Registry were available for analyses. In brief, baseline data were
      provided by the attending physician at the time of index surgery. Follow-up data
      were collected using a web-based questionnaire inquiring whether patients had
      needed revision surgery during follow-up, which was defined as the endpoint of
      the present analysis. Results: A total of 88 patients (3.3%) reported the need
      for revision surgery as early as 12 months postoperatively. Among the most common
      causes were arthrofibrosis (n = 27) and infection (n = 10). Female patients
      showed a significantly greater complication rate (4.5%) when compared with male
      patients (2.6%; P = .0071). The majority of cartilage lesions were located at the
      medial femoral condyle (40.2%), with a mean defect size of 3.5 +/- 2.1 cm2.
      Neither the location nor defect size appeared to lead to an increased revision
      rate, which was greatest after osteochondral autografts (5.2%) and autologous
      chondrocyte implantation (4.6%). Revision rates did not differ significantly
      among surgical techniques. Chi-square analysis revealed significant correlations
      between the number of previous joint surgeries and the need for revision surgery
      (P = .0203). Multivariate regression analysis further confirmed sex and the
      number of previous surgeries as variables predicting the need for early revision
      surgery. Conclusion: The low early revision rates found in this study underline
      that today's cartilage repair surgeries are mostly safe. Although invasiveness
      and techniques differ greatly among the procedures, no differences in revision
      rates were observed. Specific factors such as sex and the number of previous
      surgeries seem to influence overall revision rates and were identified as
      relevant risk factors with regard to patient safety.

PMID- 29450206
TI  - Restriction of Passive Glenohumeral Abduction Combined With Normal Passive
      External Rotation Is a Diagnostic Feature of Calcific Tendinitis.
AB  - Background: Passive glenohumeral range of motion may be characteristically
      limited to specific shoulder pathologies. While pain associated with loss of
      range of passive external glenohumeral rotation is recognized as a salient
      feature in adhesive capsulitis, restriction of glenohumeral range of motion in
      calcific tendinitis of the supraspinatus tendon has never been studied.
      Hypothesis: On the basis of clinical observation, we hypothesized that calcific
      tendinitis of the supraspinatus tendon is associated with loss of passive
      glenohumeral abduction without loss of external rotation. Study Design: Cohort
      study; Level of evidence, 3. Methods: Ranges of passive glenohumeral rotation and
      abduction, which are measured with a standardized protocol in our institution,
      were retrospectively reviewed and compared for patients diagnosed with either
      adhesive capsulitis or calcific tendinitis of the supraspinatus tendon. A total
      of 57 patients met the inclusion criteria for the calcific tendinitis, and 77 met
      the inclusion criteria for the adhesive capsulitis group. Results: When compared
      with the contralateral, unaffected shoulder, glenohumeral abduction in the
      calcific tendinitis group was restricted by a median of 10 degrees 
      (interquartile range [IQR], -20 degrees  to -5 degrees ) as opposed to
      glenohumeral external rotation, which was not restricted at all (median, 0
      degrees ; IQR, 0 degrees  to 0 degrees ). The adhesive capsulitis group showed a
      median restriction of glenohumeral abduction of 40 degrees  (IQR, -50 degrees  to
      -30 degrees ) and a median restriction of passive glenohumeral external rotation
      of 40 degrees  (IQR, -60 degrees  to -30 degrees ). Conclusion: Calcific
      tendinitis of the supraspinatus does not typically cause loss of external
      rotation but is frequently associated with mild isolated restriction of
      abduction. This finding can be used to clinically differentiate adhesive
      capsulitis from calcific tendinitis.

PMID- 29450204
TI  - PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in
      Asthma.
AB  - Asthma affects approximately 300 million people worldwide, significantly
      impacting quality of life and healthcare costs. While current therapies are
      effective in controlling many patients' symptoms, a large number continue to
      experience exacerbations or treatment-related adverse effects. Alternative
      therapies are thus urgently needed. Accumulating evidence has shown that the
      peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone
      receptors, comprising PPARalpha, PPARbeta/delta, and PPARgamma, is involved in
      asthma pathogenesis and that ligand-induced activation of these receptors
      suppresses asthma pathology. PPAR agonists exert their anti-inflammatory effects
      primarily by suppressing pro-inflammatory mediators and antagonizing the pro
      inflammatory functions of various cell types relevant to asthma pathophysiology.
      Experimental findings strongly support the potential clinical benefits of PPAR
      agonists in the treatment of asthma. We review current literature, highlighting
      PPARs' key role in asthma pathogenesis and their agonists' therapeutic potential.
      With additional research and rigorous clinical studies, PPARs may become
      attractive therapeutic targets in this disease.

PMID- 29450207
TI  - Fixation of Traumatic Chondral-Only Fragments of the Knee in Pediatric and
      Adolescent Athletes: A Retrospective Multicenter Report.
AB  - Background: While traditional biological principles have suggested that fragments
      consisting of cartilage alone cannot be reaffixed to bone with expectable long
      term healing, case reports of successful healing after fixation in younger
      patients indicate that this concept remains incompletely explored. Purpose: To
      evaluate the presenting features, techniques, healing rates, and clinical and
      radiological results in a cohort of pediatric and adolescent athletes who
      underwent fixation of traumatic chondral-only fragments in the knee. Study
      Design: Case series; Level of evidence, 4. Methods: Patient registries at 2
      tertiary care children's hospitals were reviewed to identify patients <=18 years
      old who underwent fixation of a "chondral-only" fragment in the knee, defined as
      the inability to visualize the fragment on injury radiographs or discern bone on
      the articular portion of a fragment intraoperatively. The mechanism of injury,
      fragment features, fixation technique, and postoperative clinical course,
      including timing of sports clearance, healing on postoperative magnetic resonance
      imaging (MRI), and any complications or reoperations, were assessed. Results:
      Fifteen patients with a median age at surgery of 12.7 years (interquartile range
      [IQR], 11.7-14.2 years) and median follow-up of 12.0 months (IQR, 6.0-19.2
      months) were analyzed. All patients sustained an acute knee injury before
      surgery. The injured sites, as assessed on MRI, were the patella (n = 6),
      trochlea (n = 5), and lateral femoral condyle (n = 4). The median fragment
      surface area was 492.0 mm2 (IQR, 400.0-787.5 mm2). Fixation with bioabsorbable
      implants was performed in all patients at a median of 1.6 weeks (IQR, 1.0-2.6
      weeks) after the injury. One patient (7%) sustained a fall 8 weeks
      postoperatively, requiring secondary surgery for excision of a dislodged
      fragment, and 1 patient (7%) underwent unrelated patellar stabilization surgery
      3.4 years postoperatively, at which time the fragment was found to be stable. MRI
      was performed in 9 of 14 patients with retained fragments (median, 12.0 months
      postoperatively), with 5 patients (56%) showing restoration of the cartilage
      contour and the resolution of subchondral edema; 2 patients showed thinning but
      intact cartilage, 1 had cartilage thickening, and 1 had subchondral edema,
      fissuring, and cystic changes. The median time to return to sports for all 15
      patients was 26.0 weeks (IQR, 22.8-40.9 weeks), including 2 patients who required
      second surgery and returned to sports at 26.1 and 191.1 weeks. Conclusion:
      Fixation of traumatic chondral-only fragments using bioabsorbable implants may
      result in successful short-term healing in the majority of pediatric and
      adolescent athletes.

PMID- 29450208
TI  - Clinical Outcomes After Microfracture of the Knee: Midterm Follow-up.
AB  - Background: Microfracture is a single-stage arthroscopic procedure used to treat
      small- and medium-sized cartilage defects, the clinical results of which have
      been mixed to date. Purpose: To retrospectively evaluate prospectively collected
      patient-reported outcomes (PROs) after microfracture as well as to determine
      patient-related and defect-related factors associated with clinical outcomes and
      which factors predict the need for additional surgery. Study Design: Case-control
      study; Level of evidence, 3. Methods: All patients between the ages of 10 and 70
      years who underwent microfracture by the senior author for a focal chondral
      defect of the knee between January 1, 2005, and March 1, 2010, were eligible for
      study enrollment. Patients were excluded if they underwent concomitant procedures
      that violated the subchondral bone. Functional outcomes were determined using
      preoperative and final follow-up PROs, including the Lysholm, International Knee
      Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score
      (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC),
      Short Form-12 (SF-12), and overall satisfaction scores. Patient-related factors
      (sex, age, body mass index [BMI]) and defect-related factors (lesion size,
      location, concomitant procedures, prior procedures) were analyzed for
      correlations with outcome scores. All patient-related and defect-related factors
      were also analyzed as predictors for subsequent surgery. Results: Overall, 101
      patients (102 knees; 55 male, 46 female; mean age, 35.87 +/- 12.52 years; mean
      BMI, 26.3 +/- 5.5 kg/m2; mean defect size, 2.635 +/- 1.805 cm2) were included.
      Lesion location included 44.90% at the medial femoral condyle, 21.43% at the
      trochlea, 11.22% at the lateral femoral condyle, 10.20% at multiple sites, 8.16%
      at the patella, and 4.08% at the tibial plateau. Microfracture was performed
      alone in 72 of 102 (71%) knees. At a mean follow-up of 5.66 +/- 2.54 years
      (range, 2-11 years), clinically meaningful and statistically significant
      improvements were seen in all PROs (P < .05) except the SF-12 mental component
      score. Patients who had an isolated tibial plateau defect or multiple defects
      demonstrated reduced improvements in the symptom rate (P = .0237). Patients with
      a BMI >30 kg/m2 had lower postoperative scores on the KOOS activities of daily
      living subscale (P = .0261) and poorer WOMAC function and WOMAC pain scores (P =
      .029 and .0307, respectively). Patient BMI, age, sex, defect location,
      concomitant procedures, and operative side were not significant predictors for
      additional surgery. Larger defect size (>3.6 cm2) and prior knee surgery were
      independent risk factors for additional knee surgery after microfracture.
      Conclusion: After microfracture, all PROs demonstrated clinically and
      statistically significant improvements at 5.7 years. Functionally, male patients
      benefited more from microfracture than female patients. Microfracture of tibial
      lesions and multisite microfracture provided less benefit than microfracture of
      isolated femoral defects. Larger lesion size (>3.6 cm2) and prior knee surgery
      predicted the need for additional knee surgery after microfracture.

PMID- 29450209
TI  - Creation and Assessment of a Clinical Predictive Calculator and Mortality
      Associated With Candida krusei Bloodstream Infections.
AB  - Background: Candida krusei bloodstream infection (CK BSI) is associated with high
      mortality, but whether this is due to underlying comorbidities in affected
      patients or the organism itself is unknown. Identifying patient characteristics
      that are associated with CK BSI is crucial for clinical decision-making and
      prognosis. Methods: We conducted a retrospective analysis of hospitalized
      patients with Candida BSI at our institution between 2002 and 2015. Data were
      collected on demographics, comorbidities, medications, procedures, central lines,
      vital signs, and laboratory values. Multivariable logistic and Cox regression
      were used to identify risk factors associated with CK and mortality,
      respectively. Results: We identified 1873 individual patients who developed
      Candida BSI within the study period, 59 of whom had CK BSI. CK BSI was predicted
      by hematologic malignancy, gastric malignancy, neutropenia, and the use of
      prophylactic azole antifungals, monoclonal antibodies, and beta-lactam/beta
      lactamase inhibitor combinations. The C-statistic was 0.86 (95% confidence
      interval, 0.81-0.91). The crude mortality rates were 64.4% for CK BSI and 41.4%
      for non-CK BSI. Although CK was associated with higher mortality in univariable
      Cox regression, this relationship was no longer significant with the addition of
      the following confounders: lymphoma, neutropenia, glucocorticoid use, chronic
      liver disease, and elevated creatinine. Conclusions: Six patient comorbidities
      predicted the development of CK BSI with high accuracy. Although patients with CK
      BSI have higher crude mortality rates than patients with non-CK BSI, this
      difference is not significant when accounting for other patient characteristics.

PMID- 29450210
TI  - Sofosbuvir-Based Direct-Acting Antiviral Therapies for HCV in People Receiving
      Opioid Substitution Therapy: An Analysis of Phase 3 Studies.
AB  - Background: Hepatitis C virus (HCV) direct-acting antiviral therapy is effective
      among people receiving opioid substitution therapy (OST), but studies are limited
      by small numbers of nongenotype 1 (GT1) patients. The aim of this study was to
      evaluate the treatment completion, adherence, SVR12, and safety of sofosbuvir
      based therapies in HCV patients receiving and not receiving OST. Methods: Ten
      phase 3 studies of sofosbuvir-based regimens included ION (ledipasvir/sofosbuvir
      +/- ribavirin for 8, 12, or 24 weeks in GT1), ASTRAL (sofosbuvir/velpatasvir for
      12 weeks in GT1-6), and POLARIS (sofosbuvir/velpatasvir and
      sofosbuvir/velpatasvir/voxilaprevir in GT1-6). Patients with clinically
      significant drug use (last 12 months) or noncannabinoids detected at screening
      were ineligible. Results: Among 4743 patients, 4% (n = 194) were receiving OST
      (methadone; n = 113; buprenorphine, n = 75; other, n = 6). Compared with those
      not receiving OST (n = 4549), those receiving OST (n = 194) were younger (mean
      age, 48 vs 54), more often male (73% vs 61%), GT3 (38% vs 17%), treatment-naive
      (78% vs 65%), and cirrhotic (36% vs 23%). Among those receiving and not receiving
      OST, there was no significant difference in treatment completion (97% vs 99%, P =
      .06), SVR12 (94% vs 97%, P = .06), relapse (0.5% vs 2.1%, P = .19), adverse
      events (78% vs 77%, P = .79), or serious adverse events (3.6% vs 2.4%, P = .24).
      There was no difference in SVR12 in patients with cirrhosis (99% vs 95%, P = .25)
      or those with G3 (95% vs 95%, P = .77) in those receiving OST. Among patients
      receiving OST, SVR12 was high among those receiving methadone (95%) and
      buprenorphine (96%). Conclusion: Sofosbuvir-based therapies are effective and
      safe in patients receiving OST.

PMID- 29450211
TI  - Actinotignum schaalii Infection: A Clandestine Cause of Sterile Pyuria?
AB  - Actinotignum schaalii is an underappreciated cause of urinary tract infections
      (UTIs) in older adults. The diagnosis may be missed due to difficulty isolating
      and identifying the organism. Complications can result because the organism is
      intrinsically resistant to 2 commonly used drugs to treat UTI, as illustrated by
      this case.

PMID- 29450212
TI  - Fecal Microbiota Transplant for Refractory Clostridium difficile Infection
      Interrupts 25-Year History of Recurrent Urinary Tract Infections.

PMID- 29450213
TI  - Differential Regulation of PAI-1 in Hantavirus Cardiopulmonary Syndrome and
      Hemorrhagic Fever With Renal Syndrome.
AB  - We analyzed the levels of circulating tissue plasminogen activator (tPA) and
      plasminogen activator inhibitor (PAI)-1 in acute hantavirus cardiopulmonary
      syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS). The levels of
      tPA commonly increased in both diseases, whereas PAI-1 correlated with disease
      severity in HCPS but not in HFRS.

PMID- 29450214
TI  - Mycobacterium abscessus Complex Infections: A Retrospective Cohort Study.
AB  - Background: Infections caused by Mycobacterium abscessus group strains are
      usually resistant to multiple antimicrobials and challenging to treat worldwide.
      We describe the risk factors, treatment, and clinical outcomes of patients in 2
      large academic medical centers in the United States. Methods: A retrospective
      cohort study of hospitalized adults with a positive culture for M. abscessus in
      Miami, Florida (January 1, 2011, to December 31, 2014). Demographics,
      comorbidities, the source of infection, antimicrobial susceptibilities, and
      clinical outcomes were analyzed. Early treatment failure was defined as death
      and/or infection relapse characterized either by persistent positive culture for
      M. abscessus within 12 weeks of treatment initiation and/or lack of radiographic
      improvement. Results: One hundred eight patients were analyzed. The mean age was
      50.81 +/- 21.03 years, 57 (52.8%) were females, and 41 (38%) Hispanics. Eleven
      (10.2%) had end-stage renal disease, 34 (31.5%) were on immunosuppressive
      therapy, and 40% had chronic lung disease. Fifty-nine organisms (54.6%) were
      isolated in respiratory sources, 21 (19.4%) in blood, 10 (9.2%) skin and soft
      tissue, and 9 (8.3%) intra-abdominal. Antimicrobial susceptibility reports were
      available for 64 (59.3%) of the patients. Most of the isolates were susceptible
      to clarithromycin, amikacin, and tigecycline (93.8%, 93.8%, and 89.1%,
      respectively). None of the isolates were susceptible to
      trimethoprim/sulfamethoxazole, and only 1 (1.6%) was susceptible to
      ciprofloxacin. Thirty-six (33.3%) patients early failed treatment; of those, 17
      (15.7%) died while hospitalized. On multivariate analysis, risk factors
      significantly associated with early treatment failure were disseminated infection
      (odds ratio [OR], 11.79; 95% confidence interval [CI], 1.53-81.69; P = .04),
      acute kidney injury (OR, 6.55; 95% CI, 2.4-31.25; P = .018), organ
      transplantation (OR, 2.37; 95% CI, 2.7-23.1; P = .005), immunosuppressive therapy
      (OR, 2.81; 95% CI, 1.6-21.4; P = .002), intravenous amikacin treatment (OR, 4.1;
      95% CI, 0.9-21; P = .04), clarithromycin resistance (OR,79.5; 95% CI, 6.2-3717.1,
      P < .001), and presence of prosthetic device (OR, 5.43; 95% CI, 1.57-18.81; P =
      .008). Receiving macrolide treatment was found to be protective against early
      treatment failure (OR, 0.13; 95% CI, 0.002-1.8; P = .04). Conclusions: Our cohort
      of 108 M. abscessus complex isolates in Miami, Florida, showed an in-hospital
      mortality of 15.7%. Most infections were respiratory. Clarithromycin and amikacin
      were the most likely agents to be susceptible in vitro. Resistance to
      fluoroquinolone and trimethoprim/sulfamethoxazole was highly common. Macrolide
      resistance, immunosuppression, and renal disease were significantly associated
      with early treatment failure.

PMID- 29450215
TI  - Pulmonary Cavity From Mycobacterium malmoense in an HIV-Infected Patient:
      Complicated by Bronchopleural Fistula.
AB  - We present a case of M. malmoense and HIV co-infection complicated by
      aspergilloma leading to bronchopleural fistula with intractable pneumothorax and
      pleural aspergillosis, ultimately requiring surgical intervention. Treatment
      guidelines for M. malmoense are reviewed, literature regarding M. malmoense and
      HIV co-infection is reviewed, and the epidemiology of M. malmoense in North
      America is discussed.

PMID- 29450216
TI  - A Multidisciplinary Delphi Consensus-Based Checklist to Define Clinical
      Documentation Tools for Both Routine and Research Purposes.
AB  - Background: To the best of our knowledge, a strategic approach to define the
      contents of structured clinical documentation tools for both clinical routine
      patient care and research purposes has not been reported so far, although
      electronic health record will become more and more structured and detailed in the
      future. Objective: To achieve an interdisciplinary consensus on a checklist to be
      considered for the preparation of disease- and situation-specific clinical
      documentation tools. Methods: A 2-round Delphi consensus-based process was
      conducted both with 19 physicians of different disciplines and 14 students from
      Austria, Switzerland, and Germany. Agreement was defined as 80% or more positive
      votes of the participants. Results: The participants agreed that a working group
      should be set up for the development of structured disease- or situation-specific
      documentation tools (97% agreement). The final checklist included 4
      recommendations concerning the setup of the working group, 12 content-related
      recommendations, and 3 general and technical recommendations (mean agreement
      [standard deviation] = 97.4% [4.0%], ranging from 84.2% to 100.0%). Discussion
      and Conclusion: In the future, disease- and situation-specific structured
      documentation tools will provide an important bridge between registries and
      electronic health records. Clinical documentation tools defined according to this
      Delphi consensus-based checklist will provide data for registries while serving
      as high-quality data acquisition tools in routine clinical care.

PMID- 29450217
TI  - A Cross-Sectional Assessment of Cutaneous Lumbosacral and Coccygeal Physical
      Examination Findings in a Healthy Newborn Population.
AB  - Objective. The purpose of this study is to describe the range and frequency of
      cutaneous lumbosacral and coccygeal findings encountered during the newborn
      examination in a population of apparently healthy babies, to determine if the
      prevalence of these findings is associated with race/ethnicity, and to report the
      frequency of co-occurrence of low-risk cutaneous findings. Methods. Lumbosacral
      physical findings of 1121 infants were documented on well newborns at least 35
      weeks or greater gestational age under the authors' care. The overall frequency
      of each physical finding was tabulated in addition to determining whether
      frequencies varied by race/ethnicity. Co-occurrence of the most common physical
      findings was also examined. Results. Of 1096 infants included in the study, 24.8%
      had deviated or duplicated gluteal creases, 15.6% had dimples, and 24.7% had
      lumbosacral and/or coccygeal hairiness. All racial/ethnic groups had double to
      quadruple the risk of lumbosacral hair when compared with Caucasians. A total of
      44.1% of study infants had lumbosacral/coccygeal slate-grey patches, which were
      least common in Caucasians. Seven infants had coccygeal skin tags, and 14 infants
      had lumbosacral vascular macules. Thirty-one percent had more than 1 cutaneous
      lumbosacral finding present, 24.8% had 2 findings, and 6.2% had 3 or more
      findings. Conclusion. Coccygeal dimples, increased lumbosacral and/or coccygeal
      hair, deviations and/or duplications of the gluteal crease, and lumbosacral slate
      grey patches are common in healthy newborns and vary by race/ethnicity. Eleven
      percent of study infants had 2 or more low-risk cutaneous findings excluding
      slate-grey patches. Distinction between low-risk and common versus high-risk
      findings is important when deciding which patients need further evaluation.

PMID- 29450218
TI  - Attitudes Toward FDA Regulation of Newly Deemed Tobacco Products.
AB  - Objective: To examine how smokers perceive FDA oversight of e-cigarettes, hookah,
      and cigars. Methods: Current US smokers (N = 1,520) participating in a randomized
      clinical trial of pictorial cigarette pack warnings completed a survey that
      included questions about attitudes toward new FDA regulations covering newly
      deemed tobacco products (ie, regulation of e-cigarettes, nicotine gels or liquids
      used in e-cigarettes, hookah, and cigars). Results: Between 47% and 56% of
      current smokers viewed these new FDA regulations favorably and between 17% - 24%
      opposed them. Favorable attitudes toward the regulations were more common among
      smokers with higher quit intentions (adjusted odds ratio (aOR): 1.17, 95% CI:
      1.02, 1.33) and more negative beliefs about smokers (aOR: 1.18, 95% CI: 1.05,
      1.33). Participants with higher education, higher income, and previous exposure
      to e-cigarette advertisements had higher odds of expressing positive attitudes
      toward the new FDA regulations (p < .05). Conclusions: Almost half of current
      smokers viewed FDA regulation of newly deemed tobacco products favorably. Local
      and state policy-makers and tobacco control advocates can build on this support
      to enact and strengthen tobacco control provisions for e-cigarettes, cigars, and
      hookah.

PMID- 29450219
TI  - Direct Bio-printing with Heterogeneous Topology Design.
AB  - Bio-additive manufacturing is a promising tool to fabricate porous scaffold
      structures for expediting the tissue regeneration processes. Unlike the most
      traditional bulk material objects, the microstructures of tissue and organs are
      mostly highly anisotropic, heterogeneous, and porous in nature. However,
      modelling the internal heterogeneity of tissues/organs structures in the
      traditional CAD environment is difficult and oftentimes inaccurate. Besides, the
      de facto STL conversion of bio-models introduces loss of information and piles up
      more errors in each subsequent step (build orientation, slicing, tool-path
      planning) of the bio-printing process plan. We are proposing a topology based
      scaffold design methodology to accurately represent the heterogeneous internal
      architecture of tissues/organs. An image analysis technique is used that
      digitizes the topology information contained in medical images of tissues/organs.
      A weighted topology reconstruction algorithm is implemented to represent the
      heterogeneity with parametric functions. The parametric functions are then used
      to map the spatial material distribution. The generated information is directly
      transferred to the 3D bio-printer and heterogeneous porous tissue scaffold
      structure is manufactured without STL file. The proposed methodology is
      implemented to verify the effectiveness of the approach and the designed example
      structure is bio-fabricated with a deposition based bio-additive manufacturing
      system.

PMID- 29450220
TI  - Recent Insights into Corticostriatal Circuit Mechanisms underlying Habits:
      Invited review for Current Opinions in Behavioral Sciences.
AB  - Habits have been studied for decades, but it was not until recent years that
      experiments began to elucidate the underlying cellular and circuit mechanisms.
      The latest experiments have been enabled by advances in cell-type specific
      monitoring and manipulation of activity in large neuronal populations. Here we
      will review recent efforts to understand the neural substrates underlying habit
      formation, focusing on rodent studies on corticostriatal circuits.

PMID- 29450221
TI  - Drinking game participation, gender performance and normalization of intoxication
      among Nigerian university students.
AB  - Background: Most research on drinking games (DGs) and the associated risks
      focuses on Western countries. In the Nigerian context, DGs activity has not
      attracted scholarly attention but growing media reports indicate that Nigerian
      youths play DGs, and that a number of gamers have died during or immediately
      after game-playing. Methods: Drawing on gender performance scripts, we explored
      the performance of gender through DGs practices and the factors that motivate DGs
      participation. Thirty-one in-depth interviews were conducted with male and female
      college students (aged 19-23 years) at a university in south-eastern Nigeria.
      Results: The participants discussed the popularity of the DGs that students play
      on this campus, identifying the spaces where each game is played and the
      motivations for game-playing. Collective, contextual constructions of gender
      identities through 'Fastest-Drinker' DG were identified, and the participants
      also performed gender through 'Truth-or-Dare' and 'Endurance' DGs. Men dominated
      'First-to-Finish' DGs, which are played at parties and bars, and consumed beer or
      stout, while women, who mainly played Truth-or-Dare games, drank spirits or
      sweetened alcoholic beverages. Boredom and fun seeking provoked game-playing
      among women while adherence to masculinity norms, which engendered the public
      performance of masculinity and gambling activities, motivated men to play DGs. To
      avoid 'collective shame', men's friendship groups provided support/care for
      inebriated game-playing members, but the immediacy of this support/care varied
      according to DGs type. Conclusion: DGs appear to normalize heavy drinking and the
      culture of intoxication on this campus. Measures to monitor alcohol sales outlets
      around campuses and interventions that target students' leisure spaces should be
      developed.

PMID- 29450222
TI  - Mood changes after watching pornography on the Internet are linked to tendencies
      towards Internet-pornography-viewing disorder.
AB  - Internet-pornography-viewing disorder (IPD) is considered one type of Internet
      use disorder. For IPD's development, it was assumed theoretically that a
      dysfunctional use of Internet pornography to cope with depressive mood or stress
      might be considered to be a risk factor. To address the effect of Internet
      pornography use on mood, an online study with three measuring points with a
      sample of male participants was conducted. Participants were investigated
      regarding their tendencies towards IPD, personal use of Internet pornography,
      general mood, perceived stress, and their Internet pornography use motivation.
      Moreover, participants were asked regarding their current mood, sexual arousal,
      and need to masturbate before and after they watched Internet pornography self
      determinedly in a private environment. Data showed that tendencies towards IPD
      were associated negatively with feeling generally good, awake, and calm and were
      correlated positively with perceived stress in daily life and using Internet
      pornography for excitation seeking and emotional avoidance. Self-determined use
      of Internet pornography in their private environment was accompanied by changes
      in mood and indicators of sexual arousal. Moreover, tendencies towards IPD were
      negatively related to mood before and after Internet-pornography use as well as
      an actual increase of good and calm mood. The results showed effects of watching
      Internet pornography on mood and sexual arousal which can be considered having
      reinforcing effects for the user. Thus, the results are in line with theoretical
      assumptions on IPD's development, in which the positive (and negative)
      reinforcement received by Internet-pornography use is related to cue-reactivity
      and craving reactions.

PMID- 29450223
TI  - Hangover resistance in a Canadian University student population.
AB  - Background: Resistance to alcohol hangover may be a risk factor for alcohol use
      disorder. Previous research to establish the prevalence of hangover resistance in
      a drinking population has either not used comparable intoxication levels or has
      considered hangover resistance over a limited time frame. The purpose of this
      study was to examine the prevalence of lifetime hangover negative (LHN) drinkers
      across comparable eBAC values ranging from 0 to 500 mg/dl. Methods: Students at
      an eastern Canadian university were surveyed about their heaviest drinking
      episode in the past month and indicated whether they had ever experienced a
      hangover in their lifetime (LHN) and, if they had, the hangover severity they
      experienced the next day. eBACs were calculated and the percentage of LHN
      drinkers was computed at each 10 mg/dl eBAC increment from 0 to 500 mg/dl.
      Results: Most LHN drinkers (58% female, 71% male) had an eBAC on their heaviest
      drinking occasion below 80 mg/dl. Above eBACs of 80 mg/dl, 5.8% of female and
      5.1% of male drinkers were lifetime hangover negative. Conclusions: The results
      suggest that only a small percentage of heavy drinkers lay claim to being
      lifetime hangover negative.

PMID- 29450224
TI  - Individual differences in implicit learning abilities and impulsive behavior in
      the context of Internet addiction and Internet Gaming Disorder under the
      consideration of gender.

PMID- 29450226
TI  - Alcohol reduction in the first trimester is unrelated to smoking, patient or
      pregnancy characteristics.
AB  - Introduction: Studies show alcohol-preferring mice reduce their alcohol intake
      during pregnancy; this study questions if the same is true for humans. The
      current investigation compares women's pre-pregnancy and first trimester alcohol
      consumption, examines if women with problem drinking diminish their alcohol
      intake during pregnancy, and determines if prenatal alcohol reduction is
      associated with characteristics of pregnancy, patients or smoking. Methods: 126
      participants in weeks 1-12 of pregnancy, recruited from Obstetric and Family
      Practices, completed a survey during their initial prenatal visit including two
      gender-specific AUDITs (Alcohol Use Disorders Identification Tests) querying
      current and pre-pregnancy alcohol use. AUDIT-C (AUDIT items 1-3) scores measuring
      pre-pregnancy and first trimester alcohol consumption were compared, analyzed and
      tested using general linear model repeated. A p <= 0.05 was accepted as
      significant. Results: Most participants were multiparous, Caucasian high school
      graduates experiencing nausea and vomiting. Pre-pregnancy alcohol use was
      significantly (p = 0.019, Fisher's exact) higher among women seeing
      obstetricians. Pre-pregnancy AUDIT-C scores (m (mean) = 2.22, sd (standard
      deviation) = 2.19) were significantly higher (p < 0.001) than first trimester
      scores (m = 0.143, sd = 0.532). Among 49 with pre-pregnancy AUDIT-C scores >= 3,
      45/49 (92%) reduced their alcohol use to zero during the first trimester. Age,
      race, education, marital status, parity, nausea and vomiting, gestational age and
      smoking were non-factors in score reduction. Conclusions: Women reported reducing
      their alcohol consumption during pregnancy, including those screening positive
      for pre-pregnancy problem drinking. First trimester alcohol reduction cannot be
      accounted for by smoking, patient or pregnancy characteristics; public health
      initiatives, psychological factors and hormonal mechanisms may be implicated.

PMID- 29450225
TI  - Online-specific fear of missing out and Internet-use expectancies contribute to
      symptoms of Internet-communication disorder.
AB  - Some of the most frequently used online applications are Facebook, WhatsApp, and
      Twitter. These applications allow individuals to communicate with other users, to
      share information or pictures, and to stay in contact with friends all over the
      world. However, a growing number of users suffer from negative consequences due
      to their excessive use of these applications, which can be referred to as
      Internet-communication disorder. The frequent use and easy access of these
      applications may also trigger the individual's fear of missing out on content
      when not accessing these applications. Using a sample of 270 participants, a
      structural equation model was analyzed to investigate the role of
      psychopathological symptoms and the fear of missing out on expectancies towards
      Internet-communication applications in the development of symptoms of an Internet
      communication disorder. The results suggest that psychopathological symptoms
      predict higher fear of missing out on the individual's Internet-communication
      applications and higher expectancies to use these applications as a helpful tool
      to escape from negative feelings. These specific cognitions mediate the effect of
      psychopathological symptoms on Internet-communication disorder. Our results are
      in line with the theoretical model by Brand et al. (2016) as they show how
      Internet-related cognitive bias mediates the relationship between a person's core
      characteristics (e.g., psychopathological symptoms) and Internet-communication
      disorder. However, further studies should investigate the role of the fear of
      missing out as a specific predisposition, as well as specific cognition in the
      online context.

PMID- 29450227
TI  - Smoke signals: The decline of brand identity predicts reduced smoking behaviour
      following the introduction of plain packaging.
AB  - This study tests a social identity based mechanism for the effectiveness of plain
      tobacco packaging legislation, introduced in Australia in December 2012, to
      reduce cigarette smoking. 178 Australian smokers rated their sense of
      identification with fellow smokers of their brand, positive brand stereotypes,
      quitting behaviours and intentions, and smoking intensity, both before and seven
      months after the policy change. Mediation analyses showed that smokers,
      especially those who initially identified strongly with their brand, experienced
      a significant decrease in their brand identity following the introduction of
      plain packaging and this was associated with lower smoking behaviours and
      increased intentions to quit. The findings provide the first quantitative
      evidence that brand identities may help maintain smoking behaviour, and suggest
      the role of social-psychological processes in the effectiveness of public health
      policy.

PMID- 29450228
TI  - Ordinary people associate addiction with loss of free will.
AB  - Introduction: It is widely believed that addiction entails a loss of free will,
      even though this point is controversial among scholars. There is arguably a
      downside to this belief, in that addicts who believe they lack the free will to
      quit an addiction might therefore fail to quit an addiction. Methods: A
      correlational study tested the relationship between belief in free will and
      addiction. Follow-up studies tested steps of a potential mechanism: 1) people
      think drugs undermine free will 2) people believe addiction undermines free will
      more when doing so serves the self 3) disbelief in free will leads people to
      perceive various temptations as more addictive. Results: People with lower belief
      in free will were more likely to have a history of addiction to alcohol and other
      drugs, and also less likely to have successfully quit alcohol. People believe
      that drugs undermine free will, and they use this belief to self-servingly
      attribute less free will to their bad actions than to good ones. Low belief in
      free will also increases perceptions that things are addictive. Conclusions:
      Addiction is widely seen as loss of free will. The belief can be used in self
      serving ways that may undermine people's efforts to quit.

PMID- 29450229
TI  - Addiction, cigarette smoking, and voluntary control of action: Do cigarette
      smokers lose their free will?
AB  - Opinions differ widely as to whether addicts lose the ability to control their
      behavior and employ free will. This article reviews empirical findings regarding
      multiple questions relevant to the issue of free will among addicted smokers: Is
      smoking voluntary behavior? Can people quit smoking? Why don't people quit
      smoking? Why do smokers relapse when they try to quit? Do addicted smokers suffer
      from irresistible cravings? Are there some people who cannot quit? Are there
      conditions that make resistance impossible? Why would they smoke knowing it can
      kill them? The evidence reviewed here seems most consistent with the view that
      smokers retain control over their actions but cannot easily stop having frequent
      desires to smoke.

PMID- 29450230
TI  - Do addicts have free will? An empirical approach to a vexing question.
AB  - Introduction: This paper addresses two overlapping questions: Do addicts have the
      capacity to voluntarily quit drugs? And do individuals knowingly pursue courses
      of action that they realize are bad for them, such as excessive drug use?
      Methods: I propose two testable versions of free will. First, the observation
      that activities differ in the degree to which they are susceptible to the
      influence of their consequences (e.g., costs and benefits) has proven a useful
      criterion for classifying behavior as voluntary or involuntary. Thus, we can ask
      if drug use in addicts is influenced by its consequences. For instance, do laws
      that promise legal sanctions for drug use reduce drug use in addicts? Second, the
      philosopher Harry Frankfurt proposed a definition of free will that takes into
      account desires and self-reflection. I propose that addicts who do not want to
      desire drugs and successfully stop craving drugs pass his test. Results:
      Dependence on illicit drugs typically ends after about four to six years.
      Dependence on cigarettes and alcohol persists for much longer, but most smokers
      and alcoholics eventually voluntarily quit using. Smokers and heroin addicts can
      voluntarily regulate their drug cravings as a function of the availability of
      their drug of choice. They have the capacity to pass Frankfurt's test of free
      will. Conclusions: Addicts have free will as defined by the capacity to voluntary
      quit using drugs and to voluntarily regulate their cravings.

PMID- 29450232
TI  - Predicting early onset of intoxication versus drinking-A population-based
      prospective study of Norwegian adolescents.
AB  - Aims: Recent research suggests that early onset of intoxication (EOI) may be of
      greater importance for a wide range of subsequent adverse outcomes than early
      drinking experiences without intoxication. However, research on antecedents of
      EOI is scarce. The present study identifies predictors of EOI and whether they
      differ from those of early onset of drinking (EOD). Methods: Data was drawn from
      the prospective Tracking Opportunities and Problems (TOPP) study of Norwegian
      families (n = 382), which followed up mothers and their children with six data
      collections from childhood (age 1.5) to adolescence (age 14.5). Self-reports from
      the adolescents (parenting practices, adolescent's conduct problems and friends'
      deviant behaviour) and their mothers (adolescent temperament, socio-economic
      factors and household alcohol problems) were used to identify predictors of EOI
      and EOD. Findings: A variety of temperamental, socio-economic, and family factors
      predicted EOI, whereas EOD was predicted of substantially fewer variables.
      Particularly, when controlling for relevant covariates, low levels of shyness,
      own conduct problems and having friends with deviant behaviour prospectively
      predicted EOI, but not EOD. Conclusions: Future research and prevention efforts
      should take into consideration that EOI and EOD without getting drunk appear to
      be predicted by different risk factors in childhood and adolescence.

PMID- 29450231
TI  - Free will in addictive behaviors: A matter of definition.
AB  - Certain people are at risk for using alcohol or other drugs excessively and for
      developing problems with their use. Their susceptibility might arise from a
      variety of factors, including their genetic make-up, brain chemistry, family
      background, personality and other psychological variables, and environmental and
      sociocultural variables. Moreover, after substance use has become established,
      there are additional cognitive-motivational variables (e.g., substance-related
      attentional bias) that contribute to enacting behaviors consistent with the
      person's motivation to acquire and use the substance. People who are at such risk
      are likely to choose to use addictive substances even though doing so entails
      negative consequences. In the sense of complete freedom from being determined by
      causal factors, we believe that there is no such thing as free will, but defined
      as ability to make choices from among multiple options, even though the choices
      are ultimately governed by natural processes, addicted individuals are free to
      choose. Although they might appear unable to exercise this kind of free will in
      decisions about their substance use, addictive behaviors are ultimately always
      goal-directed and voluntary. Such goal pursuits manifest considerable
      flexibility. Even some severely addicted individuals can cease their use when the
      value of continuing the use abruptly declines or when the subjective cost of
      continuing the use is too great with respect to the incentives in other areas of
      their lives. Formal treatment strategies (e.g., contingency management,
      Systematic Motivational Counseling, cognitive training) can also be used to
      facilitate this reversal.

PMID- 29450233
TI  - Pharmacogenomics-guided policy in opioid use disorder (OUD) management: An
      ethnically-diverse case-based approach.
AB  - Introduction: Opioid use disorder (OUD) is characterized by a problematic pattern
      of opioid use leading to clinically-significant impairment or distress. Opioid
      agonist treatment is an integral component of OUD management, and buprenorphine
      is often utilized in OUD management due to strong clinical evidence for efficacy.
      However, interindividual genetic differences in buprenorphine metabolism may
      result in variable treatment response, leaving some patients undertreated and at
      increased risk for relapse. Clinical pharmacogenomics studies the effect that
      inherited genetic variations have on drug response. Our objective is to
      demonstrate the impact of pharmacogenetic testing on OUD management outcomes.
      Methods: We analyzed a patient who reported discomfort at daily buprenorphine
      dose of 24 mg, which was a mandated daily maximum by the pharmacy benefits
      manager. Regular urine screenings were conducted to detect the presence of
      unauthorized substances, and pharmacogenetic testing was used to determine the
      appropriate dose of buprenorphine for OUD management. Results: At the 24 mg
      buprenorphine daily dose, the patient had multiple relapses with unauthorized
      substances. Pharmacogenetic testing revealed that the patient exhibited a
      cytochrome P450 3A4 ultrarapid metabolizer phenotype, which necessitated a higher
      than recommended daily dose of buprenorphine (32 mg) for adequate OUD management.
      The patient exhibited a reduction in the number of relapses on the
      pharmacogenetic-based dose recommendation compared to standard dosing.
      Conclusion: Pharmacogenomic testing as clinical decision support helped to
      individualize OUD management. Collaboration by key stakeholders is essential to
      establishing pharmacogenetic testing as standard of care in OUD management.

PMID- 29450234
TI  - Is the concept of compulsion useful in the explanation or description of
      addictive behaviour and experience?
AB  - The concept of compulsion, in which addictive behaviour is said to be carried out
      against the will, is central to the disease theory of addiction and ubiquitous in
      modern definitions. The aims of this article are: (i) to describe various
      meanings of compulsion in the literature; (ii) to compare the part thought to be
      played by compulsion in addiction with its suggested role in obsessive-compulsive
      disorder; (iii) to critically examine the place of compulsion in influential
      neurobiological accounts of addiction; (iv) to summarise the empirical evidence
      bearing on the usefulness of the compulsion concept, evidence that seems at first
      sight incompatible with the notion of compulsion. This is followed by a
      discussion of which possible meanings of compulsion can survive an empirical test
      and what role they might play in understanding addiction, paying particular
      attention to a distinction between strong and weak senses of compulsion. A
      conclusion is that addictive behaviour cannot be considered compulsive at the
      time it is carried out, though other possible meanings of compulsion as an
      explanation or description of addictive behaviour and experience are discussed.
      Among other conclusions, it is suggested that, although in some senses of the
      term it may seem arbitrary whether or not 'compulsion' should be retained, its
      use has important consequences for the public understanding of addiction, and is
      likely to deter people's attempts to overcome their addictions and their chances
      of success.

PMID- 29450235
TI  - Vietnamese validation of the short version of Internet Addiction Test.
AB  - Background and aims: The main goal of the present study was to examine the
      psychometric properties of a Vietnamese version of the short-version of Internet
      Addiction Test (s-IAT) and to assess the relationship between s-IAT scores and
      demographics, health related qualify of life and perceived stress scores in young
      Vietnamese. Methods: The Vietnamese version of s-IAT was administered to a sample
      of 589 participants. Exploratory factor and reliability analyses were performed.
      Regression analysis was used to identify the associated factors. Results: The two
      factor model of Vietnamese version of s-IAT demonstrated good psychometric
      properties. The internal consistency of Factor 1 (loss of control/time
      management) was high (Cronbach's alpha = 0.82) and Factor 2 (craving/social
      problems) was satisfactory (Cronbach's alpha = 0.75). Findings indicated that
      20.9% youths were addicted to the Internet. Regression analysis revealed
      significant associations between Internet addiction and having problems in self
      care, lower quality of life and high perceived stress scores. Discussion and
      conclusions: The Vietnamese version of s-IAT is a valid and reliable instrument
      to assess IA in Vietnamese population. Due to the high prevalence of IA among
      Vietnamese youths, IA should be paid attention in future intervention programs. s
      IAT can be a useful screening tool for IA to promptly inform and treat the IA
      among Vietnamese youths.

PMID- 29450236
TI  - Strong preference for mint snus flavor among research participants.
AB  - Introduction: The Family Smoking Prevention and Tobacco Control Act of 2009
      allows the US FDA to regulate tobacco products, including the banning of
      characterizing flavors, such as fruit and candy, cigarettes. The availability of
      mint flavored snus may facilitate the use of the product if consumers find it
      more palatable with respect to taste, odor, pleasantness, and intensity. Methods:
      This study assessed product evaluation (PES), odor identification, odor
      intensity, and odor hedonics among 151 smokers enrolled in a clinical trial of
      snus substitution for cigarettes. Results: Far more participants selected
      Winterchill (N = 110) than Robust (N = 41), regardless of their menthol cigarette
      smoking status. Nicotine dependence was higher among those who selected
      Winterchill (4 vs 3 on Fagerstrom scale, p = 0.017). Those who found Winterchill
      to be more satisfying, less aversive, and having a more intense, more pleasant
      odor than Robust were substantially more likely to select Winterchill for their
      one week trial. Conclusions: Findings indicate that subjective effect measures
      such as the PES and DEQ are capable of differentiating products in terms of
      flavor preference, and that smokers express a strong preference for mint flavored
      snus.

PMID- 29450237
TI  - The associations among personality, alcohol-related Protective Behavioural
      Strategies (PBS), alcohol consumption and sexual intercourse in Irish, female
      college students.
AB  - Introduction: The study presented one of the first examinations of the
      associations among personality, alcohol-related protective behavioural strategies
      (PBS), alcohol consumption, sexual intercourse and sex-related alcohol negative
      consequences in Irish, female college students (n = 522). Methods: A cross
      sectional observational design was employed and participants completed the study
      online. Participants completed measures of personality, alcohol-related PBS,
      alcohol consumption and sexual intercourse. Hierarchical multiple regression was
      utilised to access the associations between such measures. Results: From the
      analyses, it was found that age, frequency of sexual intercourse, frequency of
      alcohol consumption, level of alcohol consumption and openness were all
      significantly related to the use of alcohol-related protective behavioural
      strategies, and in turn, sex-related negative consequences. However, inconsistent
      findings with other personality dimensions to those of previous research were
      noted. Conclusions: The findings of this study posited that the use of PBS has a
      key role to play in the levels of sexual intercourse and alcohol consumption, age
      and openness, and the associated negative sexual consequences in Irish, female
      college students.

PMID- 29450238
TI  - The direct and indirect effect of loneliness on the development of adolescent
      alcohol use in the United Kingdom.
AB  - Alcohol use among adolescents in the United Kingdom (UK) remains relatively high
      compared to those in other European countries. The present study sought to
      examine both the direct and indirect effect of loneliness on drinking behavior.
      Participants were school children (mean age 13.5 years at Time 1) participating
      in a Randomized Controlled Trial in the UK, who completed a battery of
      questionnaires examining alcohol-use indicators, loneliness, self-efficacy and
      sensation seeking at Time 1 and at +12 months. Loneliness at Time 1 had a
      substantive, though largely indirect (i.e., via self-efficacy and sensation
      seeking covariates), impact on alcohol-related harm at +12 months. Furthermore,
      Loneliness interacted with gender in the prediction of context of alcohol use,
      where being female and experiencing loneliness put an individual at a greater
      risk of unsupervised drinking. Females experiencing loneliness were also 2.9
      times as likely to have had a drink in the past 30 days, and around 2.5 times as
      likely to have ever consumed a full drink, when compared to their male peers. The
      current results indicate that loneliness is an important but complex factor in
      adolescent drinking. There are important implications for the development of
      interventions to prevent underage drinking, not least that it is not appropriate
      to consider all underage drinkers as socially marginalised. However, for those
      that are, the self-medication hypothesis is potentially relevant through
      emotional self-efficacy.

PMID- 29450239
TI  - Alcohol related mental imagery: The effects of a priming dose in at risk
      drinkers.
AB  - Objectives: Drug related mental imagery is proposed to play a central role in
      addictive behaviour. However, little is known about such cognition or how it is
      pharmacologically modulated. Here, we test theoretical predictions of the
      'elaborated intrusion' theory by comparing neutral with alcohol related mental
      imagery, and examine the effects of low dose alcohol on phenomenological aspects
      of this imagery. Methods: Alcohol related and neutral imagery was assessed after
      at risk drinkers (n = 40) consumed alcohol (0.3 g/kg) or placebo, in a crossover
      design. Sensory and visuospatial qualities of imagery, along with associated
      craving, positive affect and 'mind wandering' were assessed. Results: Alcohol
      related mental imagery was rated as more vivid and sensorially rich, effects that
      were larger following the priming dose of alcohol. In addition, mind wandering
      was substantially lower during alcohol versus neutral imagery, especially after
      alcohol consumption. First person perspective was more prevalent for alcohol
      imagery after alcohol, although the Drink * Imagery type interaction did not
      reach statistical significance. However, first person imagery was associated with
      higher levels of craving during alcohol related imagery. Conclusions: Alcohol
      related mental imagery differs phenomenologically from neutral imagery on a
      number of dimensions. Priming with alcohol may enable cognitive elaboration by
      biasing the output of controlled cognitive processing towards enhanced sensory
      elaboration and increased attention to alcohol related cognition. These
      feedforward effects may be involved in focusing cognitive and behavioural
      resources on alcohol acquisition/consumption through the elaboration and
      rehearsal of relevant goals and plans.

PMID- 29450240
TI  - Improving cerebral oxygenation, cognition and autonomic nervous system control of
      a chronic alcohol abuser through a three-month running program.
AB  - The abusive use of alcohol has shown to be associated to cerebral damage,
      impaired cognition, poor autonomic nervous control, impaired cardiovascular
      health, increased levels of stress and anxiety, depression symptoms and poor
      quality of life. Aerobic exercise has shown to be an efficient tool to reduce and
      overcome these issues. In this case report, a patient (forty-four years old,
      male) under treatment in public psychiatric hospital, classified as having a
      substance use disorder, underwent a three-month running program. The maximal
      oxygen consumption increased from 24.2 ml/kg/min to 30.1 ml/kg/min, running time
      increased from 6 min to 45 min (650%) and distance covered from 765 m to 8700 m
      (1037.2%). In prefrontal cortex oxygenation, oxyhemoglobin levels improved by
      76.1%, deoxyhemoglobin decreased 96.9% and total hemoglobin increased 78.8%
      during exercise. Reaction time in the cognitive test during rest decreased 23%,
      and the number of correct answers increased by 266.6%. Parasympathetic cardiac
      parameters increased in several heart rate variability indices. Thus, we conclude
      that running exercise performed by an alcoholic patient hospitalized in a
      psychiatric hospital improves cerebral function, cognition and cardiovascular
      health.

PMID- 29450241
TI  - Smartphone addiction, daily interruptions and self-reported productivity.
AB  - The advent of the smartphone has dramatically altered how we communicate,
      navigate, work and entertain ourselves. While the advantages of this new
      technology are clear, constant use may also bring negative consequences, such as
      a loss of productivity due to interruptions in work life. A link between
      smartphone overuse and loss of productivity has often been hypothesized, but
      empirical evidence on this question is scarce. The present study addressed this
      question by collecting self-report data from N = 262 participants, assessing
      private and work-related smartphone use, smartphone addiction and self-rated
      productivity. Our results indicate a moderate relationship between smartphone
      addiction and a self-reported decrease in productivity due to spending time on
      the smartphone during work, as well as with the number of work hours lost to
      smartphone use. Smartphone addiction was also related to a greater amount of
      leisure time spent on the smartphone and was strongly related to a negative
      impact of smartphone use on daily non-work related activities. These data support
      the idea that tendencies towards smartphone addiction and overt checking of the
      smartphone could result in less productivity both in the workplace and at home.
      Results are discussed in relation to productivity and technostress.

PMID- 29450242
TI  - One-year abstinence improves ADHD symptoms among patients with polysubstance use
      disorder.
AB  - Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common
      comorbid disorder in patients suffering from substance use disorder (SUD).
      Individuals with co-occurring SUD and ADHD are more likely than SUD patients
      without ADHD to have developed SUD at a younger age, be polysubstance users, and
      need inpatient treatment more often. The present study investigates whether
      individuals with polysubstance use disorder who remain abstinent for a year after
      entering treatment have a more substantial reduction in ADHD symptoms than those
      who relapsed and controls. Material and methods: Subjects were SUD patients (N =
      115) and healthy controls (N = 34). ADHD symptoms were assessed using the adult
      ADHD Self-Report Scale (ASRS). Substance use was assessed by self-reports on the
      Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders
      Identification Test (DUDIT). Participants were defined as having relapsed if they
      had an AUDIT score >= 8 or a DUDIT score >= 2 for women and >= 6 for men.
      Results: Patients who remained abstinent for one year reported a substantial
      reduction of ADHD symptoms compared to patients who relapsed and controls.
      Conclusions: Abstinence alleviates ADHD symptoms among patients with
      polysubstance use disorder. We suggest that confirmation of an ADHD diagnosis
      should follow a period of abstinence to avoid identification of false-positive
      cases.

PMID- 29450243
TI  - Is exercise addiction in fitness centers a socially accepted behavior?
AB  - Background: Fitness exercise is popular and associated with improved health and
      social status. Taken to extremes, however, exercise can become an addiction. One
      suggested symptom of exercise addiction is "conflicts" with family and friends.
      However, it may be difficult to recognize excessive exercise patterns if they are
      accepted and encouraged by relatives. The aim of this study was to explore if
      fitness exercisers with a high risk of addiction experienced the same level of
      exercise support as exercisers with a low risk of addiction. Furthermore, we
      wanted to examine if social support affected the subjective reporting of
      "conflicts". Method: A total of 577 fitness exercisers completed the Exercise
      Addiction Inventory (EAI) and two questions asking about "exercise support from
      family and friends" and "present eating disorder". Results: Exercisers at high
      risk of exercise addiction reported the same level of support from relatives as
      those at low risk. Exercisers with high levels of exercise support reported
      significantly fewer conflicts, even if they were at high risk of addiction. If an
      eating disorder was present, the level of exercise support was significantly
      reduced. Conclusion: Exercise addiction might be difficult to identify with the
      general behavioral addiction symptom "conflict", since exercise is socially
      accepted even in subjects with high risk of exercise addiction. If an eating
      disorder is present, the exercise routines seem to be interpreted as socially
      undesirable. Screening for exercise addiction with the EAI should take into
      account that fitness exercisers rarely report conflicts, which could result in
      false negative cases.

PMID- 29450244
TI  - Characteristics of adherence to methadone maintenance treatment over a 15-year
      period among homeless adults experiencing mental illness.
AB  - Background: Methadone maintenance treatment (MMT) has important protective
      effects related to reduced illicit opioid use, infectious disease transmission,
      and overdose mortality. Adherence to MMT has not been examined among homeless
      people. We measured MMT adherence and reported relevant characteristics among
      homeless adults experiencing mental illness in Vancouver, British Columbia,
      Canada. Material and methods: Homeless adults living with mental illness who had
      received MMT prior to the baseline interview of the Vancouver At Home study (n =
      78) were included in analyses. The medication possession ratio (MPR) was used to
      estimate MMT adherence from retrospective administrative pharmacy and public
      health insurance data collected across 15 years. Independent sample t tests and
      one-way ANOVA were used to test for significant differences in MMT MPR by
      participant characteristics. Results: Mean MMT MPR was 0.47. A large proportion
      of participants reported blood-borne infectious disease, three or more chronic
      physical health conditions, and substance use. Being single and never married was
      associated with significantly lower MMT MPR (0.40 vs. 0.55, p = 0.036), while
      living with schizophrenia, bipolar disorder, or a mood disorder with psychotic
      features was associated with significantly higher MMT MPR (0.54 vs. 0.37, p =
      0.022). Daily drug use (excluding alcohol) was associated with significantly
      lower MMT MPR (0.39 vs. 0.54, p = 0.051). Conclusions: The level of adherence to
      MMT was very low among homeless adults experiencing mental illness. Efforts are
      needed to improve adherence to MMT as a means of reducing illicit substance use,
      preventing overdose deaths, and attenuating infectious disease transmission.

PMID- 29450245
TI  - Video game addiction and psychological distress among expatriate adolescents in
      Saudi Arabia.
AB  - Introduction: Few studies have estimated screen time among Arab adolescents, and
      no studies, to date, have published data on addiction to video games or Internet
      games among Arab adolescents. This study aimed to assess the prevalence of
      addiction to video games and its correlation with mental health in a sample of
      expatriate high school students from the Al-Qassim region of Saudi Arabia.
      Methods: The survey was conducted in 2016 among 276 students enrolled in ninth
      through twelfth grades in the International Schools in Buraidah, Al-Qassim.
      Students who returned signed consent forms from their parents filled out a self
      administered questionnaire that included validated scales on addiction to video
      games, general health, and lifestyle. Results: The proportion between the sexes
      and the schools were roughly equal. Around 32% were overweight or obese, 75% had
      screen time >= 2 h/day, and 20% slept < 5 h/night. Sixteen per cent (16%) were
      addicted to video games and 54% had psychological distress. Addiction to video
      games was strongly associated with psychological distress (OR = 4.1, 95% CI =
      1.80, 9.47). Other significant correlates were female gender, higher screen time,
      and shorter sleep hours. Conclusions: The proportion of students with
      psychological distress was high. Future studies should investigate other
      potential correlates of distress such personal traits, family relations, and
      academic performance.

PMID- 29450246
TI  - Validation of a Swedish version of the short UPPS-P impulsive behavior scale
      among young adults.
AB  - The UPPS-P model of impulsivity proposes that impulsivity comprises five distinct
      facets-negative urgency, positive urgency, lack of premeditation, lack of
      perseverance, and sensation seeking. The UPPS-P Impulsive Behavior Scale has been
      used to measure these facets. The purpose of the current study was to develop and
      evaluate the psychometric properties of a Swedish version of the 20-item UPPS-P
      Impulsive Behavior Scale (SUPPS-P). The sample comprised 343 Swedish young adults
      (Mage = 24.21, SD = 2.01; 27% men, 2% other or undisclosed gender identity) who
      answered a questionnaire including the SUPPS-P; Depression, Anxiety, and Stress
      Scale (DASS-21); and questions regarding their alcohol consumption and substance
      use. Confirmatory factor analysis supported a 5-factor, inter-correlated model,
      where each subscale of the SUPPS-P constitutes one latent variable. The
      convergent validity was established by replicating previously found correlations
      between the different impulsivity facets and depression, anxiety, frequency of
      alcohol consumption, and substance use. The internal consistency was acceptable
      for all the SUPPS-P subscales (Cronbach's alpha = 0.65-0.78, McDonald's omega =
      0.65-0.79), except lack of perseverance (Cronbach's alpha = 0.60, McDonald's
      omega = 0.61). Thus, while the Swedish version of the SUPPS-P is suitable for
      assessing impulsivity in Swedish young adult samples, further research is needed
      to improve the psychometric properties of the lack of perseverance subscale.

PMID- 29450247
TI  - The association between financial literacy and Problematic Internet Shopping in a
      multinational sample.
AB  - Purpose: To examine the association between financial literacy and Problematic
      Internet Shopping in adults. Methods: This cross-sectional online survey
      recruited participants, aged between 18 and 60 years, through an online research
      facility. The sample consisted of multinational participants from mainly three
      continents including Europe, North America, and Asia. Problematic Internet
      Shopping was assessed using the Bergen Shopping Addiction Scale (BSAS). Financial
      Literacy was measured by the Financial Literacy subscale of the Financial
      Wellbeing Questionnaire. Multiple linear regression analyses were conducted to
      elucidate the relationship between the study and outcome variables with
      adjustment for other potential risk factors. Results: Of the total of 997
      respondents with an average age of 30.9 (s.d. = 8.8), 135 (13.8%) could be
      classified as having a high risk of being Problematic Internet Shoppers. Results
      from the multiple regression analyses suggested a significant and negative
      relationship between financial literacy and Problematic Internet Shopping with a
      regression coefficient of - 0.13, after controlling for the effects of potential
      risk factors such as age, region of birth, employment, income, shopping
      frequency, self-regulation and anxiety (t = - 6.42, p < 0.001). Conclusions: The
      clinical management of PIS should include a financial counselling as a component
      of the treatment regime. Enhancement of financial literacy in the general
      population, particularly among young people, will likely have a positive effect
      on the occurrence of PIS.

PMID- 29450248
TI  - Metacognitions or distress intolerance: The mediating role in the relationship
      between emotional dysregulation and problematic internet use.
AB  - Objective: Given the relevance of problematic Internet use (PIU) to everyday
      life, its relationship to emotional dysregulation and the importance of
      metacognitions and distress intolerance in process and intermediaries research,
      this study examined which of metacognitions and distress intolerance acts as an
      intermediary between emotional dysregulation and PIU. Methods: In the current
      study, 413 undergraduate students from the University of Tehran, Iran (202
      females; mean age = 20.13) voluntarily completed a questionnaire package which
      included the Internet Addiction Test (IAT), Difficulties in Emotion Regulation
      Scale (DERS), Metacognitions Questionnaire 30 (MCQ-30(, and Distress Tolerance
      Scale (DTS). The data were then analyzed using structural equation modeling by
      LISREL software. Results: Significant correlations were found between PIU and
      emotional dysregulation and both distress intolerance and metacognitions (P <
      0.001). Structural equation modeling and path analysis results fit well to the
      data (chi2/df = 1.73; p < 0.001; RMSEA = 0.05; SRMR = 0.04; CFI = 0.97; NFI =
      0.95). The results of the mediational model indicated that emotional
      dysregulation has an indirect impact via metacognition (beta = 0.31; SE = 0.02)
      and distress tolerance (beta = - 0.60; SE = 0.03) on PIU. The analysis also
      revealed a significant direct impact of emotional dysregulation on PIU, although
      this impact is much less than the indirect impact. The variables in this model
      accounted for 62% of the variance in participants' PIU levels. Conclusion: The
      results of this study provide evidence for the impact of emotional dysregulation
      on PIU through metacognitions and distress intolerance. Also, these findings
      emphasize that distress intolerance has a more significant mediating role than
      metacognition in the relationship between emotional dysregulation and PIU.

PMID- 29450249
TI  - Towards an understanding of self-directed language as a mechanism of behavior
      change: A novel strategy for eliciting client language under laboratory
      conditions.
AB  - Introduction: Change talk (CT) and sustain talk (ST) are thought to reflect
      underlying motivation and be important mechanisms of behavior change (MOBCs).
      However, greater specificity and experimental rigor is needed to establish CT and
      ST as MOBCs. Testing the effects of self-directed language under laboratory
      conditions is one promising avenue. The current study presents a replication and
      extension of research examining the feasibility for using simulation tasks to
      elicit self-directed language. Methods: First-year college students (N = 92)
      responded to the Collegiate Simulated Intoxication Digital Elicitation, a
      validated task for assessing decision-making in college drinking. Verbal
      responses elicited via free-response and structured interview formats were coded
      based on established definitions of CT and ST, with minor modifications to
      reflect the non-treatment context. Associations between self-directed language
      and alcohol use at baseline and eight months were examined. Additionally, this
      study examined whether a contextually-based measure of decision-making,
      behavioral willingness, mediated relationships between self-directed language and
      alcohol outcome. Results: Healthy talk and unhealthy talk independently were
      associated with baseline alcohol use across both elicitation formats. Only
      healthy talk during the free-response elicitation was associated with alcohol use
      at follow up; both healthy talk and unhealthy talk during the interview
      elicitation were associated with 8-month alcohol use. Behavioral willingness
      significantly mediated the relationship between percent healthy talk and alcohol
      outcome. Conclusions: Findings support the utility of studying self-directed
      language under laboratory conditions and suggest that such methods may provide a
      fruitful strategy to further understand the role of self-directed language as a
      MOBC.

PMID- 29450250
TI  - Association between drug use and urban violence: Data from the II Brazilian
      National Alcohol and Drugs Survey (BNADS).
AB  - Objective: To investigate the association of alcohol and cocaine use with urban
      violence (both as victim and as perpetrator) in a representative sample of the
      Brazilian population. Method: The Second Brazilian Alcohol and Drugs Survey (II
      BNADS) interviewed 4607 individuals aged 14 years and older from the Brazilian
      household population including an oversample of 1157 adolescents (14 to 18 years
      old). The survey gathered information on alcohol, tobacco and illegal substances
      use as well as on risk factors for abuse and dependence, behaviors associated
      with the use of substances and the possible consequences, as urban violence
      indicators. Results: Approximately 9.3% of the Brazilian population has been
      victim of at least one form of urban violence. This proportion increases to 19.7%
      among cocaine users and to 18.1% among individuals with alcohol use disorders
      (AUD). Perpetration of violence was reported by 6.2% of the sample. Cocaine use
      and AUD increased in almost four times the chances of being an aggressor. Being
      religious and married decreased the chances of being a victim and/or perpetrador
      of urban violence. Higher education also decreased the chances of involvement in
      both victimization or perpetration of violence. Both Parallel Mediation Models
      considering cocaine use as a predictor of urban violence (victimization or
      perpetration) were valid and alcohol consumption and depressive symptoms were
      mediators of this relationship. Conclusions: This study presents relevant data of
      interest to Brazil as this country is one of the major consumer market of cocaine
      and also is among the most violent countries worldwide.

PMID- 29450251
TI  - Online activities, prevalence of Internet addiction and risk factors related to
      family and school among adolescents in China.
AB  - Aims: To investigate the online activities, prevalence of Internet Addiction in
      relation to demographic characteristics and risk factors related to family and
      school among adolescents. Methods: A total of 6468 10-18 year old adolescents
      recruited from local schools in Guangzhou, China were selected by adopting multi
      stage stratified random sampling (female/male: 2886/3582; mean age:13.78 +/-
      2.43). Participants completed a structured questionnaire. Results: The overall
      prevalence of Internet Addiction was 26.50%, with severe addiction being 0.96%.
      Internet Addiction was higher among males than females (30.6% versus 21.2%).
      Older grade students reported more Internet addiction rate (chi2 = 431.25, P <
      0.001). The five highest-ranked online activities were social networking
      (94.73%), school work (86.53%), entertainment (82.44%), Internet gaming (73.42%)
      and shopping online (33.67%). A negative relationship with teachers (OR: 1.35,
      95% CI: 1.20-1.53), a negative relationship between two parents (OR: 1.23, 95%
      CI: 1.18-1.37), and poor academic performance (OR: 1.22, 95% CI: 1.17-1.35),
      showed the highest relative risks for Internet addiction. Conclusions: Severe
      Internet Addiction is not common, but mild Internet addiction was reported by
      more than one fourth of all participants. The rates of Internet Addiction varied
      by gender, grade, the quality of family relationships and school situation,
      suggesting these factors should be considered when designing and implementing
      interventions.

PMID- 29450252
TI  - Alcohol and tobacco use among methadone maintenance patients in Vietnamese rural
      mountainside areas.
AB  - Introduction: The expansion of methadone maintenance treatment (MMT) program
      requires more data about the factors affecting the effectiveness of treatment,
      especially behavioral data such as smoking and alcohol use among patients. This
      study aimed to examine the prevalence of tobacco and alcohol consumption and
      identify related factors among MMT patients in the Vietnamese rural mountainside.
      Methods: We interviewed 241 MMT patients in two clinics in Tuyen Quang, a
      mountainous province in Vietnam. Patients were asked to report the smoking status
      (current smoker or not), nicotine dependence (by Fagerstrom test for nicotine
      dependence - FTND) and alcohol use (by using the Alcohol Use Disorders
      Identification Test - AUDIT-C). EuroQol-5 dimensions-5 levels (EQ-5D-5L) and EQ
      Visual analogue scale (EQ-VAS) were employed to measure health-related quality of
      life. Multivariate logistic and Tobit regressions were used to identify the
      associated factors. Results: The majority of respondents were current smokers
      (75.7%) and a low proportion were hazardous drinkers (18.3%). People receiving
      treatment in a rural clinic (OR = 0.45; 95%CI = 0.22-0.92) and had problems in
      usual activities (OR = 0.20; 95%CI = 0.06-0.70) were less likely to be smokers. Q
      VAS score (Coef. = 0.03; 95%CI = 0.02-0.05) and having problems in mobility
      (Coef. = 0.72; 95%CI = 0.03-1.42) was found to be associated with the increase of
      nicotine dependence. In terms of alcohol drinking, people with other jobs were
      more likely to drink hazardously compared to unemployed patients (OR = 2.86;
      95%CI = 1.20-6.82). Similarly, patients having higher duration of MMT had higher
      likelihood of being hazardous drinkers (OR = 1.07; 95%CI = 1.01-1.13).
      Conclusions: This study highlights the low rate of alcohol abusers but a
      considerably high proportion of current smokers among MMT patients in the rural
      mountainside area. Alcohol and tobacco counseling programs combined with social
      and family support also play an essential role in alcohol and tobacco control. In
      addition, implementing mass community-based behavioral change campaigns to reduce
      drug addiction-related stigmatization should also be prioritized.

PMID- 29450253
TI  - Drug, nicotine, and alcohol use among exercisers: Does substance addiction co
      occur with exercise addiction?
AB  - Background: Scholastic works suggest that those at risk for exercise addiction
      are also often addicted to illicit drugs, nicotine, and/or alcohol, but empirical
      evidence is lacking. Aims: The aim of the present work was to examine the co
      occurrence of illicit drug, nicotine, and alcohol use frequency (prevalence of
      users) and severity (level of problem in users) among exercisers classified at
      three levels of risk for exercise addiction: (i) asymptomatic, (ii) symptomatic,
      and (iii) at-risk. Methods: A sample of 538 regular exercisers were surveyed via
      the Qualtrics research platform. They completed the (i) Drug Use Disorder
      Identification Test, (ii) Fagerstrom Test for Nicotine Dependence, (iii) Alcohol
      Use Disorder Identification Test, and (iv) Exercise Addition Inventory. Results:
      A large proportion (n = 59; 10.97%) of the sample was found to be at risk for
      exercise addiction. The proportion of drug and alcohol users among these
      participants did not differ from the rest of the sample. However, the incidence
      of nicotine consumption was lowest among them. The severity of problematic
      substance use did not differ across the groups. Conclusions: These findings
      suggest that substance addiction and the risk for exercise addiction are
      unrelated. In fact, those at risk for exercise addiction exhibited the healthiest
      profile related to the prevalence of smoking.

PMID- 29450254
TI  - Correlates of cannabis vape-pen use and knowledge among U.S. college students.
AB  - Introduction: The proliferation of electronic devices, such as vape-pens, has
      provided alternative means for cannabis use. Research has found cannabis-vaping
      (i.e., vape-pen use) is associated with lower perceived risks and higher cannabis
      use. Knowledge of these products may increase likelihood of subsequent use. As
      policies for cannabis shift, beliefs that peers and family approve of this
      substance use (injunctive norms) increase and there has been an increase in vape
      pen use among young adults (18-35 year olds); however, correlates thereof remain
      unknown. Young adults often engage in cross-substance use with cannabis and
      alcohol, making alcohol a potential correlate of cannabis vape-pen use and
      knowledge. Therefore, we examined alcohol use and other potential correlates of
      vape-pen use and knowledge among a sample of university students. Methods: This
      secondary data analysis utilized surveys at multiple colleges in the U.S. (N =
      270). Alcohol use, social anxiety, cannabis expectancies, injunctive and
      descriptive norms and facets of impulsivity were examined as correlates of vape
      pen use and knowledge using bivariate correlations and logistic regressions.
      Results: Alcohol use was correlated with cannabis vape-pen use and knowledge.
      Frequency of cannabis use, peer injunctive norms, and positive expectancies were
      associated with increased likelihood of vape-pen use. Lack of premeditation, a
      facet of impulsivity, was associated with cannabis vape-pen knowledge.
      Conclusions: Given the unknown nature and consequences of cannabis vape-pens, the
      present findings offer valuable information on correlates of this behavior.
      Further, correlates of knowledge of vape-pens may point to areas for education
      and clinical intervention to prevent heavy cannabis vape-pen use.

PMID- 29450255
TI  - Anterior insula activation during inhibition to smoking cues is associated with
      ability to maintain tobacco abstinence.
AB  - Relapse to smoking after initial abstinence is a major clinical challenge with
      significant public health consequences. At the brain and behavioral level, those
      who relapse to tobacco smoking have both greater cue-reactivity and lower
      inhibitory control than those who remain abstinent. Little is known about neural
      activation during inhibitory control tasks in the presence of drug-related cues.
      In the current study, tobacco smokers (SMK; n = 22) and non-smoking controls
      (CON; n = 19) completed a Go/NoGo task involving smoking cues during a functional
      magnetic resonance imaging (fMRI) scan. Following the scan session, smokers were
      required to quit smoking, and maintenance of abstinence was evaluated as part of
      a 12-week smoking cessation trial. We evaluated pre-cessation brain activity
      during NoGo trials in smokers who were versus were not able to quit smoking. We
      then compared fMRI and inhibitory control measures between smokers and non
      smokers. We did not find differences between SMK and CON in performance or
      activation to smoking or neutral cues. However, compared to SMK who relapsed, SMK
      who attained biochemically-validated abstinence at the end of the smoking
      cessation trial had greater neural activation in the anterior insula during NoGo
      trials specifically with smoking-related cues. Results indicate that within SMK,
      decreased inhibitory control activation during direct exposure to drug-related
      stimuli may be a marker of difficulty quitting and relapse vulnerability.

PMID- 29450256
TI  - Creation and validation of the barriers to alcohol reduction (BAR) scale using
      classical test theory and item response theory.
AB  - Those who binge drink are at increased risk for alcohol-related consequences when
      compared to non-binge drinkers. Research shows individuals may face barriers to
      reducing their drinking behavior, but few measures exist to assess these
      barriers. This study created and validated the Barriers to Alcohol Reduction
      (BAR) scale. Participants were college students (n = 230) who endorsed at least
      one instance of past-month binge drinking (4+ drinks for women or 5+ drinks for
      men). Using classical test theory, exploratory structural equation modeling found
      a two-factor structure of personal/psychosocial barriers and perceived program
      barriers. The sub-factors, and full scale had reasonable internal consistency
      (i.e., coefficient omega = 0.78 (personal/psychosocial), 0.82 (program barriers),
      and 0.83 (full measure)). The BAR also showed evidence for convergent validity
      with the Brief Young Adult Alcohol Consequences Questionnaire (r = 0.39, p <
      .001) and discriminant validity with Barriers to Physical Activity (r = -0.02, p
      = .81). Item Response Theory (IRT) analysis showed the two factors separately met
      the unidimensionality assumption, and provided further evidence for severity of
      the items on the two factors. Results suggest that the BAR measure appears
      reliable and valid for use in an undergraduate student population of binge
      drinkers. Future studies may want to re-examine this measure in a more diverse
      sample.

PMID- 29450257
TI  - Succinylated chitosan derivative has local protective effects on intestinal
      inflammation.
AB  - We have previously reported on the anti-inflammatory effects of a water-soluble
      chitosan derivative, zwitterionic chitosan (ZWC). In the present study, we
      hypothesized that orally-administered ZWC would provide local anti-inflammatory
      effects in the intestinal lumen. ZWC indeed showed anti-inflammatory effects in
      various in-vitro models including peritoneal macrophages, engineered THP1
      monocytes, and Caco-2 cells. In Caco-2 cells, ZWC applied before the
      lipopolysaccharide (LPS) challenge was more effective than when it was applied
      after it in preventing LPS-induced cell damage. When administered to mice via
      drinking water as a prophylactic measure, ZWC protected the animals from 2,4,6
      trinitrobenzene sulphonic acid (TNBS)-induced colitis, helping them to recover
      the body weight, restore the gross and histological appearance of the colon, and
      generate FoxP3+ T cells. In contrast, orally-administered ZWC did not protect the
      animals from LPS-induced systemic inflammation. These results indicate that
      orally-administered ZWC reaches the colon with minimal absorption through the
      upper gastrointestinal tract and provides a local anti-inflammatory effect.

PMID- 29450259
TI  - Hand-Assisted Laparoscopic Partial Nephrectomy for Large Renal Carcinoma with
      Succinate Dehydrogenase Deficiency.
AB  - Background: Germline mutations in succinate dehydrogenase (SDH) are associated
      with multifocal cancers: pituitary gland tumors, pheochromocytomas,
      paragangliomas, gastrointestinal stromal tumors, and renal-cell carcinomas
      (RCCs). SDH-deficient renal-cell carcinoma (SDH-RCC) was first identified in 2004
      as an inherited kidney cancer with mutations in the SDH gene. SDH consists of A,
      B, C, and D units. Mutation in the SDHB gene is the most common mutation in SDH
      deficient RCCs. Case Presentation: We report a case of a 51-year-old healthy man
      diagnosed with SDHB germline mutation and RCCs. Positron emission
      tomography/computed tomography (PET/CT) showed a 12 cm tumor in the upper pole of
      the left kidney. A hand-assisted laparoscopic partial nephrectomy was performed
      and the histopathology of the tumor showed SDH-deficient RCC with clear surgical
      margins. Six months after the initial presentation, the patient had a slightly
      impaired renal function and was disease-free on PET/CT. Conclusion: Patients with
      SDH-deficient RCC are at risk of multifocal kidney tumors and should be offered
      lifelong follow-up. To preserve the renal function, nephron-sparing surgery is
      the choice of treatment when feasible, regardless of tumor size.

PMID- 29450258
TI  - The Cannabinoids Delta8THC, CBD, and HU-308 Act via Distinct Receptors to Reduce
      Corneal Pain and Inflammation.
AB  - Background and Purpose: Corneal injury can result in dysfunction of corneal
      nociceptive signaling and corneal sensitization. Activation of the
      endocannabinoid system has been reported to be analgesic and anti-inflammatory.
      The purpose of this research was to investigate the antinociceptive and anti
      inflammatory effects of cannabinoids with reported actions at cannabinoid 1
      (CB1R) and cannabinoid 2 (CB2R) receptors and/or noncannabinoid receptors in an
      experimental model of corneal hyperalgesia. Methods: Corneal hyperalgesia
      (increased pain response) was generated using chemical cauterization of the
      corneal epithelium in wild-type (WT) and CB2R knockout (CB2R-/-) mice. Cauterized
      eyes were treated topically with the phytocannabinoids Delta8
      tetrahydrocannabinol (Delta8THC) or cannabidiol (CBD), or the CBD derivative HU
      308, in the presence or absence of the CB1R antagonist AM251 (2.0 mg/kg i.p.), or
      the 5-HT1A receptor antagonist WAY100635 (1 mg/kg i.p.). Behavioral pain
      responses to a topical capsaicin challenge at 6 h postinjury were quantified from
      video recordings. Mice were euthanized at 6 and 12 h postcorneal injury for
      immunohistochemical analysis to quantify corneal neutrophil infiltration.
      Results: Corneal cauterization resulted in hyperalgesia to capsaicin at 6 h
      postinjury compared to sham control eyes. Neutrophil infiltration, indicative of
      inflammation, was apparent at 6 and 12 h postinjury in WT mice. Application of
      Delta8THC, CBD, and HU-308 reduced the pain score and neutrophil infiltration in
      WT mice. The antinociceptive and anti-inflammatory actions of Delta8THC, but not
      CBD, were blocked by the CB1R antagonist AM251, but were still apparent, for both
      cannabinoids, in CB2R-/- mice. However, the antinociceptive and anti-inflammatory
      actions of HU-308 were absent in the CB2R-/- mice. The antinociceptive and anti
      inflammatory effects of CBD were blocked by the 5-HT1A antagonist WAY100635.
      Conclusion: Topical cannabinoids reduce corneal hyperalgesia and inflammation.
      The antinociceptive and anti-inflammatory effects of Delta8THC are mediated
      primarily via CB1R, whereas that of the cannabinoids CBD and HU-308, involve
      activation of 5-HT1A receptors and CB2Rs, respectively. Cannabinoids could be a
      novel clinical therapy for corneal pain and inflammation resulting from ocular
      surface injury.

PMID- 29450260
TI  - Achieving a 'top-down' change agenda by driving and supporting a collaborative
      'bottom-up' process: case study of a large-scale enhanced recovery programme.
AB  - There is increasing recognition that organisations need to look beyond their
      boundaries for new innovations. However, the introduction and implementation of
      best practice that has been developed externally may need different processes of
      implementation if a successful change process is going to be achieved. Using an
      enhanced recovery programme as an example, we report a case study that combines
      the best of a top-down approach with the principles of bottom-up collaborative
      working to successfully embed a large-scale quality improvement programme that
      was commissioned to improve the adoption of enhanced recovery in elective
      surgery. We describe a large-scale change programme that was established,
      coordinated and driven from within a central 'top' organisation but delivered and
      owned locally by individual organisations working collaboratively across
      southeast region of England. We discuss why we believe our methodology of
      implementing this programme was successful, the important triggers for success
      and the lessons we learned from the programme.

PMID- 29450261
TI  - Improving time efficiency gathering equipment in the treatment room.
AB  - Each junior doctor spends on average 29 hours a year just accessing treatment
      rooms and approximately 4 working days per year collecting equipment. We
      identified areas where time efficiency could be improved: accessing treatment
      room door codes, standardising access to equipment in treatment rooms throughout
      the hospital, implementing the 'procedure-specific' tray (one tray per procedure
      which includes all needed equipment in one place) and indexing equipment. Our aim
      was to reduce the time taken to collect equipment, promote best practice and aid
      timely medical intervention. We collected data from 24 junior doctors with a
      Likert scale questionnaire, which confirmed the problem. We then designed an
      experiment where we timed healthcare professionals accessing treatment rooms with
      no prior knowledge of the codes and then with codes provided securely on our
      hospital-issued iPad. We project a time saving of 703 hours (88 working days) at
      Northampton General Hospital (NGH) over 1 year. We then implemented our prototype
      'procedure-specific trays' for common procedures (cannulation, lumbar puncture,
      catheter). We calculated how much time was saved when collecting equipment using
      our indexed 'procedure-specific' tray method compared with current practice.
      Based on our piloted trays, we project to save a total of 802 hours (100 working
      days) at NGH over 1 year. To finalise our project, we trialled our custom design
      trays based on our prototype for cannulation and demonstrated a time saving of
      97% relative improvement: from 225 s to 7 s. According to these results, once
      full roll of 'procedure-specific tray' is achieved, the trust will save projected
      L30 100 per year (based on average junior doctor salary of L20 per hour).

PMID- 29450262
TI  - Improving access to City and Hackney adult mental health services.
AB  - City and Hackney Adult Mental Health Referral and Assessment Service (CHAMHRAS)
      is the single point of entry for all mental health referrals to secondary
      services, with the exception of perinatal referrals, in the City and Hackney
      region of London, UK. CHAMHRAS was established in 2013 with the objective of
      providing a one-stop point of referral which screens urgent and non-urgent
      referrals of adults aged 18-65 to mental health services. This single point of
      entry simplifies the referral process to secondary mental health services
      something service users have requested. It also enables rapid feedback on all
      referrals taken from general practitioners as well as other sources. The
      centralised nature of CHAMHRAS has also facilitated the monitoring of waiting
      times from receipt of referral to first face-to-face assessment across services.
      It was noted that the waiting time for the majority of patients was exceeding the
      28-day target set by local commissioners. Indeed, in December 2014, only 30% of
      patients were being seen within this time frame. The aim of this quality
      improvement project has been to decrease the average waiting time from referral
      to first face-to-face assessment, and concomitantly increase the proportion of
      patients being assessed within the 28-day target period. The team identified
      potential sources of delay in the process of handling referrals, from receipt and
      triage, to forwarding to the relevant secondary service, and have tested change
      ideas such as the implementation of daily meetings to review referrals and the
      centralisation of appointment bookings to streamline the processes and minimise
      delays. The average waiting time from referral to first face-to-face assessment
      decreased by 34% and the proportion of patients being assessed within 28 days
      increased accordingly, exceeding 95% in the case of referrals from general
      practitioners (GP). We have listed changes that we intend to introduce with the
      aim of bringing waiting times down further.

PMID- 29450263
TI  - Improving the completeness of acute kidney injury follow-up information in
      hospital electronic discharge letters.
AB  - Objectives: Acute kidney injury (AKI) is common in hospitalised patients, often
      mandates changes to regular medications and can be unresolved at hospital
      discharge. General practitioners (GPs) require apposite AKI-related information
      in electronic discharge letters (EDLs). In 2015 NHS England introduced a care
      quality standard that all EDLs should include four items of information for
      patients with AKI. We performed a 12-month quality improvement project (QIP)
      aimed at achieving above 90% compliance with the quality standard. Methods:
      Hospital-wide episodes of AKI were detected using the nationally approved
      electronic AKI alerts system. 25 patient AKI episodes were audited per month for
      12 months using the electronic patient record. The target compliance rate was
      staggered at 35%, 65% and 90% for each subsequent 3-month block. Baseline
      compliance was 22%. Measures taken to improve compliance included email
      information, grand rounds, ward-level meetings, computer screensavers, nurse
      support, clinical governance meetings, and face-to-face rapid education.
      Annotation of AKI within the computer EDL system was progressively enhanced such
      that in the final quarter the presence of an AKI-alert mandated the user to
      complete the AKI annotation before the EDL could be signed off. Results: The
      completion rate improved to 37% in the second quarter, 51% in the third quarter
      and 92% in the fourth quarter. This change has been sustained in the 14 months
      since. Conclusions: By the end of the study, omissions relating to AKI
      information were reduced from 78% to less than 10%, indicating our QIP was highly
      effective-meeting the quality standard. The single most important factor in
      improving documentation was to mandate user review of AKI aftercare in patients
      with electronic AKI alerts. Our study encompassed hospital-wide inpatients, and
      our results could be replicated at other acute hospitals that have implemented an
      EDL system connected to an AKI alert system.

PMID- 29450264
TI  - Improving handover between triage and locality wards in a large mental health
      trust.
AB  - Background: South London and Maudsley NHS Foundation Trust is the largest mental
      health trust in the UK, serving four boroughs in South East London. In 2014, the
      'triage ward' system was introduced in three boroughs. Similar to an acute
      medical admission unit, the triage ward would rapidly assess and treat all new
      admissions. The patients would either be discharged or admitted to a 'locality
      ward' for further treatment. Problem: The unforeseen consequences of the 'triage
      ward' system were duplications and omissions of medical tasks on receiving wards,
      which affected efficiency and quality of care. This was due to a lack of formal
      medical handover. We aimed to improve efficiency and patient safety by
      formalising the junior doctor handover between triage and locality wards,
      ensuring every patient transferred had a documented handover in their electronic
      notes. Method: We consulted our colleagues with a survey, ascertaining their
      views on the current system, the need for a more formalised system and what form
      that system should take. Using their feedback, we devised a handover template, to
      be completed for all patients transferred to locality wards. We then rolled the
      project out to the other two boroughs using the same methodology. Results: A
      follow-up survey showed improvement in our baseline results and that the majority
      of transferred patients were formally handed over. Serious incident data showed a
      decrease in incident rates pre-intervention and post-intervention. The
      intervention was sustained a year later. The transfer of the intervention to
      other sites was problematic. Discussion: The project showed the lack of handover
      was a concern shared by colleagues, and they considered our template a useful way
      of addressing this. The results suggested that the intervention was sustainable
      despite frequent rotations of staff. The difficulties in transferring an
      intervention to new sites are discussed.

PMID- 29450265
TI  - London Transfer Project: improving handover documentation from long-term care
      homes to hospital emergency departments.
AB  - About one-quarter of all long-term care (LTC) residents are transferred to an
      emergency department (ED) every 6 months in Ontario, Canada. When residents are
      unable to describe their health issues, ED staff rely on LTC transfer reports to
      make informed decisions. However, transfer information gaps are common, and may
      contribute to unnecessary tests, unwanted treatments and longer ED length of
      stay. London Health Sciences Centre, an academic hospital system in London,
      Ontario, partnered with 10 LTC homes to improve emergency reporting of their
      residents' reason for transfer and baseline cognition. After conducting a root
      cause analysis, 7 of 10 homes implemented a standard minimum set of currently
      available transfer forms, including a computer-generated summary of resident's
      most recent interRAI functional assessment. Results were analysed using
      statistical process control charts and data were posted on a public website
      (LondonTransferProject.com). The documentation rate of 'reason for transfer'
      improved from 61% to 84%, and 'baseline cognitive status' improved from 4% to 56%
      across all 10 homes. These results suggest that transfer communication can be
      improved by codesigning and implementing solutions with ED and LTC staff, which
      build upon current reporting practices shared across multiple LTC organisations.

PMID- 29450266
TI  - Collaborative approach to reducing cardiac arrests in an acute medical unit.
AB  - Cardiac arrests are often preceded by a period of physiological deterioration.
      Preventing potentially avoidable cardiac arrests therefore depends on reliable
      recognition of, and response to, those deteriorations. Our hospital's acute
      medical unit had one of the highest rates of cardiac arrest in our organisation
      at baseline. The aim was to reduce our unit's cardiac arrest rate by over 50%.
      Pareto chart analysis identified unreliable processes in the recognition and
      response to deteriorating patients. Process mapping exercises were performed,
      then the model for improvement and rapid cycle tests of change were used to
      develop standardised processes for clinical observations, recognising
      deteriorating patients and responding to hypoxia. Multidisciplinary learning from
      what went well, incorporating resilience engineering principles, helped to
      identify good practice and then test ways of making good practice happen more
      reliably. Learning from success also addressed some of the psychological barriers
      to change by encouraging pride in work and a positive focus within our unit. The
      cardiac arrest rate reduced from 4.3/1000 (October 2014 to February 2016) to
      1.1/1000 (March 2016 to end of 2016), associated with improved reliability of the
      following process measures: reliability of clinical observations, documentation
      of target oxygen saturations, identification of hypoxia and completion of
      structured response to hypoxia. This study is an example of a multidisciplinary
      team engaging in quality improvement, identifying their own local problems and
      testing their solutions scientifically. Learning from what went well had a
      positive impact on the project, and the team plans to spread the successful
      interventions across the organisation.

PMID- 29450267
TI  - Fall risk and prevention agreement: engaging patients and families with a
      partnership for patient safety.
AB  - Significance and background: Falls are multifactorial in medical oncology units
      and are potentiated by an older adult's response to anxiolytics, opiates and
      chemotherapy protocols. In addition, the oncology patient is at an increased risk
      for injury from a fall due to coagulopathy, thrombocytopenia and advanced age. At
      our National Cancer Institute-designated inpatient cancer treatment centre
      located in the southeastern USA, 40% of the total discharges are over the age of
      65. As part of a comprehensive fall prevention programme, bimonthly individual
      fall reports have been presented with the Chief Nursing Officer (CNO), nursing
      directors, nurse managers, physical therapists and front-line providers in
      attendance. As a result of these case discussions, in some cases, safety
      recommendations have not been followed by patients and families and identified as
      an implication in individual falls. Impulsive behaviour was acknowledged only
      after a fall occurred. A medical oncology unit was targeted for this initiative
      due to a prolonged length of stay. This patient population receives
      chemotherapeutic interventions, management of oncological treatment consequences
      and cancer progression care. Purpose: The aim of this project was to explore if
      initiation of a Fall Prevention Agreement between the nursing team and older
      adults being admitted to medical oncology units would reduce the incidence of
      falls and the incidence of falls with injury. Interventional methods: In order to
      promote patient and family participation in the fall reduction and safety plan,
      the Fall Risk and Prevention Agreement was introduced upon admission. Using the
      Morse Fall Scoring system, patient's risk for fall was communicated on the Fall
      Risk and Prevention Agreement. Besides admission, patients were reassessed based
      on change of status, transfer or after a fall occurs. Evaluation/findings: Fall
      and fall injuries rates were compared two-quarters prior to implementation of the
      fall agreement and eight-quarters post implementation. Falls and fall injuries on
      the medical oncology unit had an overall reduction of 37% and 58.6%,
      respectively. Discussion/implications: A robust fall prevention standard does not
      ensure care team participation in all elements to reduce fall occurrence.
      Historically, the Fall Risk and Prevention Agreement had not been initiated on
      admission. Incorporating patients and families in discussions related to fall
      risk and prevention is consistent with collaborative communication. The Joint
      Commission and the Centers for Medicare and Medicaid Services in 2002 encouraged
      patients and family participation in the acute care experience to promote safety.
      The medical oncology patient in many cases on admission is identified as
      'moderate' risk for fall. It is during the course of treatment and an extended
      length of stay that deconditioning and treatment side effects result in a fall.
      This patient population often overestimates their abilities and functional
      status.Engagement with patients and families during the admission process will
      hopefully communicate the need for a collaborative effort for fall prevention
      during the hospitalisation. Although this project is limited in data, integrating
      patients and families into care planning may have a significant impact in
      reducing falls in the 'moderate' risk patient. Additional studies including a
      multivariate analysis are needed to determine whether supporting evidence links
      fall reduction to the presence and use of a patient and family agreement.

PMID- 29450268
TI  - Patient-centred improvement to repeat prescribing using the Always Event concept.
AB  - Repeat prescriptions are prescriptions issued to a patient for a second or
      subsequent time without requiring a consultation with a doctor. Repeat
      prescribing is common and an efficient system is necessary to deliver a high
      quality service. Always Events can be used to drive patient-centred improvements
      in healthcare delivery. Our aim was to use the Always Event concept to improve
      our repeat prescribing system. This quality improvement project was carried out
      in a deprived, inner-city general practice setting in Glasgow, UK. 51 patients
      taking repeat medications completed short questionnaires, and the Always Event
      'Repeat prescriptions should be ready and available to collect' was generated. We
      used the Plan-Do-Study-Act cycles to elucidate how our system could be improved
      and check if our intervention was effective. Over a 3-day period in July 2016,
      269 out of 292 prescriptions (92.1%) were ready. We mapped out the repeat
      prescribing process and discovered that sometimes reception staff graded a
      request as inappropriate, for example, requested too early, and these requests
      were therefore not processed. Patients would then attend to collect a
      prescription that was not there. This was both inconvenient for the patient and
      time-consuming for the reception staff to investigate the reason. Our system was
      changed so that any request that was not being processed was recorded and the
      patient informed. In September 260 out of 267 (97.4%) prescriptions were ready,
      in November 350 out of 364 (96.2%), and in February 2017 314 out of 323 (97.2%)
      were ready. In conclusion, the Always Event approach allowed us to elicit
      important feedback from patients to identify a weakness in our repeat prescribing
      system, which was simple to rectify and led to an improved, more efficient
      service.

PMID- 29450269
TI  - Improving the ability to review preoperative radiographs intraoperatively in
      trauma and orthopaedic theatres at Lancashire teaching hospitals.
AB  - Background: The ability to review preoperative radiographs during trauma and
      orthopaedic surgery is essential for the surgeon to provide optimum treatment to
      the patient. However, due to current information technology (IT) systems, screen
      savers frequently interrupt the ability to review images and theatre staff are
      not routinely available to deactivate the screen-saver. This prolongs theatre
      time for the patient and affects the quality of care provided. The aim of this
      quality improvement project was to improve the availability of radiographs for
      the surgeon to review intraoperatively. Method/results: Data were collected from
      all trauma and orthopaedic theatres at two hospital sites covering all
      subspecialties and including emergency and elective cases. Baseline measurements
      showed that the frequency of preoperative radiographs not interrupted during an
      operation was 0% (0/50). Following this the Trust's IT systems were improved to
      prevent activation of the screen-saver on the theatre computers using the generic
      theatre login details. After the first-cycle intervention, data were collected
      showing 52% (14/27) of preoperative radiographs were not interrupted by a screen
      saver. The cause for this result being less than expected was investigated and
      found to be due to an alternative computer login being used on the theatre
      computers at one of the hospital sites. Education of theatre staff was then
      undertaken to ensure the correct theatre login was used and notices to remind
      staff placed on the theatre computers. After the second-cycle intervention, data
      were collected showing that 100% (26/26) of preoperative radiographs were not
      interrupted during operative time allowing the surgeon to review images when
      required. Conclusion/implications: This quality improvement project has made
      changes to theatre IT systems and practices of theatre staff which has resulted
      in a significant improvement in the ability for the operating surgeon to review
      preoperative radiographs intraoperatively.

PMID- 29450270
TI  - A local quality initiative to improve follow-up times for patients with heart
      failure.
AB  - Introduction Heart failure is the most common cause of hospital admission in
      patients >65 years and around 50% of patients will be readmitted within 6 months.
      Inability to achieve timely outpatient follow-up may contribute to the high rates
      of avoidable rehospitalisation for this group of patients. Canadian guidelines
      recommend patients with heart failure should be seen within 14 days of discharge.
      Methods An audit demonstrated that less than half of advanced heart failure
      patients were being followed up within 14 days. In an effort to improve
      postdischarge follow-up in our heart function clinic, we used process mapping and
      applied a series of iterative changes to the appointment booking system using
      Plan-Do-Study-Act cycles to reduce waste and standardise. Results The primary
      outcome measure, tracked over a period of 20 months, was percentage of patients
      booked within 14 days. At baseline, 37% of patients were seen within 14 days.
      After our series of interventions related to streamlining and standardising the
      appointment booking process, 77% of patients were seen within 14 days and 100% of
      patients were seen within 21 days. Conclusion The changes made to the appointment
      booking process were reproducible, sustainable, effective and required no
      additional resources or funding.

PMID- 29450271
TI  - Improving monitoring of diabetic complications in home care patients.
AB  - Introduction: Uncontrolled diabetes mellitus can lead to microvascular and
      macrovascular complications. Early detection of complications is necessary to
      prevent end-organ damage and reduce diabetes-related morbidity. In Qatar, the
      Home Health Care Services of Hamad Medical Corporation caters to about 1000
      patients, who solely depend on home healthcare physicians for primary care
      coordination, which includes management of chronic medical illnesses such as
      diabetes, stroke, hypertension and anaemia. Due to physician shortage, different
      physicians new to home care cover patients on different days. This leads to
      inconsistency of monitoring for many chronic conditions including diabetes and
      its complications. In this context, we conducted a quality improvement project to
      improve compliance to monitoring of diabetes complications in Home Healthcare
      Services by the implementation of a checklist. Methods: We initially collected
      baseline data on monitoring of diabetes complications by chart review. Quality
      improvement principles and methods were employed to develop a checklist-based
      intervention to improve screening of diabetes complications by healthcare staff.
      Results: Following the intervention, checklist completion rate improved from 0%
      36% in 3 months to 63% in 2 years. The healthcare staff's knowledge of monitoring
      for diabetes complications improved significantly across all monitored
      parameters. Furthermore, the percentage of patients being monitored for diabetes
      complications (ie, outcomes) also improved substantially. Monitoring for
      proteinuria and diabetic retinopathy improved from 10% and 17% at baseline to 85%
      and 74% 2 years postintervention, respectively. Conclusion: In conclusion,
      quality improvement methods were successfully used to improve monitoring of
      diabetes complications according to international guidelines in a very vulnerable
      population.

PMID- 29450272
TI  - Evaluation of a newly introduced tonsillectomy operation record for the analysis
      of regional post-tonsillectomy bleed data: a quality improvement project at the
      London North West Healthcare NHS Trust.
AB  - The primary objective of this audit and quality improvement project was to
      retrospectively analyse regional post-tonsillectomy haemorrhage data as per
      national recommendations. However, this process highlighted the need for high
      quality routinely collected data; something that was not always available via
      retrospective audit and thus does not enable formal aetiological factor analyses.
      We therefore created further secondary objectives to facilitate our primary audit
      objective. These secondary objectives were (1) to introduce a standardised
      tonsillectomy operation proforma to improve completeness and quality of routinely
      collected data and (2) to evaluate and validate proforma use and usefulness in
      improving using routine data collection to help with a repeated audit of post
      tonsillectomy haemorrhages with the eventual aim to help improve operative
      outcomes by identifying potential associated factors. The retrospective audit
      component, the prospective audit and the quality improvement component were all
      carried out at the Northwick Park Hospital and Central Middlesex Hospital (London
      North West Healthcare NHS Trust). First, 642 tonsillectomy records (2012-2014)
      were retrospectively reviewed. Free-text operative documentation and, where
      possible, potential factors associated with post-tonsillectomy haemorrhages were
      analysed. In addition, completeness of data available before and after the
      introduction of (A) a new paper-based and (B) electronic surgical record proforma
      was reviewed (2014-2015). Over a 2-year period, 62 of the 642 (9.7%) audited
      tonsillectomy patients had a post-tonsillectomy haemorrhage, and 19 of these
      (2.9%) had to return to theatre for surgical arrest of the haemorrhage. Bipolar
      diathermy was the most commonly used technique. During this period, data
      available from routine operative documentation in the surgical operation notes
      were variable and thus did not allow identification of potential factors
      associated with post-tonsillectomy haemorrhage. The completeness and quality of
      data significantly improved after the introduction of a standardised paper-based
      proforma with sections for required details based on known risk factors for post
      tonsillectomy haemorrhage and required operative details. Quality and
      completeness of data was further improved after the introduction of an electronic
      version. This electronic proforma will allow prospective spiral auditing results,
      early identification of raised bleeding rate, and provide individual surgeon
      audit results.

PMID- 29450273
TI  - Effectiveness of a multi-component quality improvement intervention on rates of
      hyperglycaemia.
AB  - Purpose: To evaluate the effectiveness of a multifaceted, hospital-wide glycaemic
      control quality improvement programme. Methods: The quality improvement
      intervention comprised three components, derived through root cause analysis:
      standardising and simplifying care (including evidence-based order sets),
      increasing visibility (through provider access to clinical data and direct
      feedback) and educational outreach (directed at the entire institution).
      Effectiveness was determined at a single urban acute care hospital through time
      series analysis with statistical process control charts. Primary outcomes
      included rate of hyperglycaemia and rate of hypoglycaemia. Results: The study
      included 70 992 hospital admissions for 50 404 patients, with 3 35 645 patient
      days. The hyperglycaemia ratio decreased 25.2% from 14.1% to 10.5% (95% CI 3.3 to
      3.9 percentage points, p<0.001). The ratio of patient days with highly elevated
      blood glucose (>299 mg/dL) decreased 31.8% from 4.8% to 3.3% (95% CI 1.4 to 1.7
      percentage points, p<0.001). Hypoglycaemia ratio decreased from 5.2% to 4.6% (95%
      CI 0.27 to 0.89 percentage points, p<0.001) in patients with diabetes, but
      increased in patients without diabetes from 1.2% to 1.7% (95% CI 0.46 to 0.70
      percentage points, p<0.001). Conclusions: We demonstrate improved hospital-wide
      glycaemic control after a multifaceted quality improvement intervention in the
      context of strong institutional commitment, national mentorship and Lean
      management.

PMID- 29450274
TI  - Strengthening value-based medication management in a free clinic for the
      uninsured: Quality interventions aimed at reducing costs and enhancing adherence.
AB  - Skyrocketing costs of prescription medications in the USA pose a significant
      threat to the financial viability of safety net clinics that opt to supply
      medications at low to no out-of-pocket costs to patients. At the East Harlem
      Health Outreach Partnership clinic of the Icahn School of Medicine at Mount
      Sinai, a physician-directed student-run comprehensive primary care clinic for
      uninsured adults of East Harlem, expenditures on pharmaceuticals represent nearly
      two-thirds of annual costs. The practice of minimising costs while maintaining
      quality, referred to as high-value care, represents a critical cost-saving
      opportunity for safety net clinics as well as for more economical healthcare in
      general. In this paper, we discuss a series of quality improvement initiatives
      aimed at reducing pharmacy-related expenditures through two distinct yet related
      mechanisms: (A) promoting value-conscious prescribing by providers and (B)
      improving patient adherence to medication regimens. Interventions aimed at
      promoting value-conscious prescribing behaviour included blacklisting a costly
      medication on our clinic's formulary and adding a decision tree in our mobile
      clinician reference application to promote value-conscious prescribing.
      Interventions targeted to improving patient adherence involved an automated text
      messaging system with English and Spanish refill reminders to encourage timely
      pick-up of medication refills. As a result of these processes, the free clinic
      experienced a 7.3%, or $3768, reduction in annual pharmacy costs. Additionally,
      medication adherence in patients with diabetes on oral antihyperglycaemic
      medications increased from 55% to 67%. Simultaneous patient-based and provider
      based interventions may be broadly applicable to addressing rising pharmacy costs
      in healthcare across the USA.

PMID- 29450275
TI  - Improving cardiac operating room to intensive care unit handover using a
      standardised handover process.
AB  - Handovers from the cardiovascular operating room (CVOR) to the cardiovascular
      intensive care unit (CVICU) are complex processes involving the transfer of
      information, equipment and responsibility, at a time when the patient is most
      vulnerable. This transfer is typically variable in structure, content and
      execution. This variability can lead to the omission and miscommunication of
      critical information leading to patient harm. We set out to improve the quality
      of patient handover from the CVOR to the CVICU by introducing a standardised
      handover protocol. This study is an interventional time-series study over a 4
      month period at an adult cardiac surgery centre. A standardised handover protocol
      was developed using quality improvement methodologies. The protocol included a
      handover content checklist and introduction of a formal 'sterile cockpit'
      timeout. Implementation of the protocol was refined using monthly iterative Plan
      Do-Study-Act. The primary outcome was the quality of handovers, measured by a
      Handover Score, comprising handover content, teamwork and patient care planning
      indicators. Secondary outcomes included handover duration, adherence to the
      standardised handover protocol and handover team satisfaction surveys. 37
      handovers were observed (6 pre intervention and 31 post intervention). The mean
      handover score increased from 6.5 to 14.0 (maximum 18 points). Specific
      improvements included fewer handover interruptions and more frequent
      postoperative patient care planning. Average handover duration increased slightly
      from 2:40 to 2:57 min. Caregivers noted improvements in teamwork, content
      received and patient care planning. The majority (>95%) agreed that the
      intervention was a valuable addition to the CVOR to CVICU handover process.
      Implementation of a standardised handover protocol for postcardiac surgery
      patients was associated with fewer interruptions during handover, more reliable
      transfer of critical content and improved patient care planning.

PMID- 29450276
TI  - Nurse-managed transitional beds as a method of increasing geographic placement of
      an academic inpatient service.
AB  - Geographic placement of patients in hospitals has long been valued to bring
      together all healthcare members as a team focused on high-quality patient-centred
      care. This goal can be particularly challenging for physicians whose patients are
      often scattered across various hospital units. The inpatient medicine service for
      the Palmetto Health-University of South Carolina Internal Medicine Residency
      Program began attempting geographic placement when a model for team-based care
      was adopted in 2015, but despite various process improvements we found it very
      difficult to maintain a high census of our patients on the unit. We eventually
      came up with an innovative solution to the problem that incorporated the use of
      transition beds-beds dedicated for patients moving onto or out of the unit in
      order to make it easier for the unit to control patient flow. We saw an immediate
      increase in our average census from ~8 to ~15 patients as well as a major shift
      of the median admission time to 3.5 hours earlier in the day. Unfortunately, it
      was an added burden to our already stressed charge nurses, and when the pilot
      ended we were forced to end the use of the transition beds. Despite our
      challenges, we applied valuable lessons learnt that have helped us in other
      improvement projects, and overall we did successfully demonstrate that transition
      beds are a viable option for an inpatient medical unit to improve geographic
      placement of patients while optimising patient flow.

PMID- 29450277
TI  - A quality improvement project to improve the Medicare and Medicaid Services (CMS)
      sepsis bundle compliance rate in a large healthcare system.
AB  - Sepsis is a leading cause of mortality and morbidity in hospitalised patients.
      The Centers for Medicare and Medicaid Services (CMS) mandated that US hospitals
      report sepsis bundle compliance rate as a quality process measure in October
      2015. The specific aim of our study was to improve the CMS sepsis bundle
      compliance rate from 30% to 40% across 20 acute care hospitals in our healthcare
      system within 1 year. The study included all adult inpatients with sepsis sampled
      according to CMS specifications from October 2015 to September 2016. The CMS
      sepsis bundle compliance rate was tracked monthly using statistical process
      control charting. A baseline rate of 28.5% with 99% control limits was
      established. We implemented multiple interventions including computerised
      decision support systems (CDSSs) to increase compliance with the most commonly
      missing bundle elements. Compliance reached 42% (99% statistical process control
      limits 18.4%-38.6%) as CDSS was implemented system-wide, but this improvement was
      not sustained after CMS changed specifications of the outcome measure.
      Difficulties encountered elucidate shortcomings of our study methodology and of
      the CMS sepsis bundle compliance rate as a quality process measure.

PMID- 29450278
TI  - Improving referral to psychological support unit at Saudi Red Crescent Authority
      in Riyadh Region.
AB  - The Psychological Support Unit (PSU) performance in Saudi Red Crescent Authority
      (SRCA) showed that only a small number of case referred seeking psychological
      advice and management from PSU among all SRCA employees. However, research shows
      that between 28% and 52% of emergency medical services (EMS) providers usually
      seek psychological help in various EMS cultures, where 86% of them usually suffer
      from critical stress. Thus, we decided to design a quality improvement project
      that aims to improve the referral process by increasing cases referred to the PSU
      at SRCA in Riyadh Region by 75% in 2 months. A multidisciplinary team has been
      formed to analyse the problem using quality tools including, brainstorming,
      fishbone diagram and flow chart of the PSU processes. Several possible reasons
      have been identified, such as lack of awareness among the SRCA's employees about
      PSU and its services, and the concern about privacy and confidentiality during
      psychological consultations in the PSU, in addition to the long referring process
      to PSU. The team decided to test the following change ideas: increasing the
      awareness of employees about the PSU services, improving the privacy and
      confidentiality during the consultation using electronic channels, and finally re
      engineering the referral process to make it lean and remove all the unnecessary
      steps. Several improvement interventions have been tested sequentially in three
      consecutive Plan-Do-Study-Act cycles on a weekly basis. The project findings
      demonstrated that the first change idea was successful but not reaching the
      target while the second change had led to huge impact exceeding our target but
      with short effect. On the other hand, although the third change idea of re
      engineering the PSU referral process had led to negative result initially, over
      the following weeks of measurement the results turned to be positive and meeting
      our expectations. We concluded that re-engineering referral process is most
      effective improvement intervention among other change ideas in term of magnitude
      and sustainability of the effect on increasing the number of referral cases to
      the PSU. We recommend conducting further testing and measuring of these change
      ideas in other PSU across the SRCA to understand the diffident context in other
      regions of SRCA.

PMID- 29450279
TI  - Improving a process to obtain hepatitis B serology among patients treated with
      infliximab at a large urban children's hospital.
AB  - Background: Hepatitis B infection is a significant public health challenge
      despite improvements in vaccination efforts. Patients such as those on chronic
      immunosuppressive therapy for inflammatory bowel disease (IBD) or rheumatic
      disease may incur greater risk. The risk of reactivation of hepatitis B while on
      immunosuppressive therapy may have mortality rates up to 25%. These patients
      should be screened for acute or chronic infection and vaccinated if necessary.
      Our aim was to reliably complete hepatitis B screenings in patients receiving
      infliximab at Cincinnati Children's Hospital Medical Center (CCHMC). Methods:
      Eligible patients included all patients with gastroenterology (GI) IBD and
      rheumatology receiving infliximab between October 2015 and March 2016. Using
      quality improvement methodology and the 'plan-do-study-act' (PDSA) approach,
      interventions centred around education of clinical providers, previsit planning
      and the development of 'talking points' for patients. Results: An initial screen
      of the IBD population revealed that 48% of the IBD patient population had been
      screened for anti-HBs alone, but no patients from GI or rheumatology divisions
      had a complete set of hepatitis B serology prior to the intervention including
      anti-Hep B Core and Hep B Surface Antigen. Seven PDSA cycles were performed
      during the 32-week intervention period, resulting in an increase in patients
      screened from 0% to ~85%. By March 2016, a total of 251 patients (201 GI, 50
      rheumatology) had up-to-date hepatitis B serology screening. Automated ordering
      of the hepatitis B serology and 'talking points' for the provider had the
      greatest impact on successful screening. Conclusions: We developed a method to
      obtain hepatitis B serology on at-risk patients on infliximab within two
      subspecialty divisions within a large children's hospital. Next steps will be to
      develop a process to reliably provide vaccines for patients who are seronegative,
      expand this process to all patients who are identified as immunocompromised
      within GI and rheumatology and then expand this process to other divisions at the
      CCHMC.

PMID- 29450280
TI  - Improving the patient booking service to reduce the number of missed appointments
      at East London NHS Foundation Trust Community Musculoskeletal Physiotherapy
      Service.
AB  - The East London National Health Service Foundation Trust (ELFT) Community
      Musculoskeletal (MSK) Physiotherapy Service had reported a high rate of non
      attendance at scheduled appointments. This was leading to delayed access to
      treatment for patients and a reduced capacity for service users, as well as a
      waste of clinical resources. The aim of this quality improvement project was
      therefore to reduce the percentage of missed appointments within this department.
      This study was undertaken by the ELFT community MSK service, with support from
      the ELFT Quality Improvement team. To begin with, patient complaints were
      explored; these indicated that the main reason for missing appointments was due
      to issues with the patient booking service. Baseline data were initially
      collected for both new referrals and follow-up patients. The proposed changes
      were then introduced, which included text message reminders, first via a manual
      platform and then via an automated system. Ongoing data were recorded to note the
      effectiveness of these changes. Following the intervention, non-attendance of
      newly referred patients reduced by 43.35% (23.76%-13.46%) after both cycles. Non
      attendance of follow-up patients reduced by 44.14% (23.74%-13.26%) after the
      second cycle alone. By listening to the opinions of service users, it was
      possible to improve the patient booking system and the flexibility of
      appointments. This resulted in a reduction in the percentage of appointments
      missed. These changes will continue to be monitored within this department to
      ensure sustainability but there is also now potential for similar interventions
      to be trialled in other health service departments.

PMID- 29450281
TI  - Improving communication between obstetric and neonatology teams for high-risk
      deliveries: a quality improvement project.
AB  - Summoning is a key component of communication between obstetrics and neonatal
      resuscitation team (NRT) in advance of deliveries. A paging system is a commonly
      used summoning tool. The timeliness and information contained in the page help
      NRT to optimally prepare for postdelivery infant care. Our aim was to increase
      the frequency that summoning pages contained gestational age and reason for NRT
      attendance to >90%. At baseline, 8% of pages contained gestational age and 33% of
      pages contained a reason for NRT attendance. Sequential Plan-Do-Study-Act cycles
      were used as our model for quality improvement. During the 8-month improvement
      period, the per cent of pages increased to 97% for gestational age and 97% for
      reason for NRT attendance. Measures of page timeliness, our balancing measure,
      did not change. Summoning communication between obstetric and NRT is crucial for
      optimal perinatal outcomes. The active involvement of all stakeholders throughout
      the project resulted in the development of a standardised paging tool and a more
      informative paging process, which is a key communication tool used in many
      centres.

PMID- 29450282
TI  - Implementation of a mock root cause analysis to provide simulated patient safety
      training.
AB  - Background: The proposed revision to the Accreditation Council for Graduate
      Medical Education (ACGME) Common Program Requirements includes participation in
      real or simulated patient safety activities, such as root cause analysis (RCA).1
      Because exposure to RCA may occur with low frequency, a mock RCA was developed
      and piloted for feasibility with Hematology/Oncology fellows. Objective: To
      improve trainee knowledge of the goals and application of RCA in patient safety
      and quality improvement through a simulated experience. Methods: A mock RCA was
      implemented with Hematology/Oncology fellows over two subsequent years. In small
      groups, they reviewed a case involving an adverse event and identified sources of
      harm. Additional details, in the form of provider interviews, were available upon
      request. Trainees identified the root cause(s) and proposed measurable changes.
      Teams presented proposals to peers and a panel representing hospital leadership.
      Feedback was provided. Trainees completed evaluations and were surveyed regarding
      their perceptions. Results: Thirteen of 15 fellows completed the survey. Twelve
      of 13 (92%) fellows felt the mock RCA improved their comfort level for
      participation in a real RCA. Ten of 13 fellows (77%) reported increased awareness
      and likelihood of reporting near misses and/or adverse events following
      participation. More thorough patient care documentation following the session was
      reported by 8 of 13 (62%). Conclusion: A pilot trial of a mock RCA with
      Hematology/Oncology fellows had high trainee satisfaction. Post-session surveys
      and informal interviews suggest trainees have reduced anxiety when faced with
      participation in a real RCA and have more interest in the process after
      participation.

PMID- 29450283
TI  - Improving best possible medication history with vulnerable patients at an urban
      safety net academic hospital using pharmacy technicians.
AB  - Background: Best possible medication history (BPMH) enhances the care of safety
      net patients, especially those with limited English proficiency and limited
      health literacy who are most vulnerable to medication error during the hospital
      admission process. Our large urban academic safety net centre faced numerous
      barriers to achieve BPMH among hospitalised patients including communication
      barriers that increase the time and complexity of eliciting BPMH, frequent
      provider turnover at our training institution and lack of an electronic health
      record (EHR) medication reconciliation tool to facilitate BPMH collection and
      monitoring. Design: Leveraging opportunities afforded by the US federal incentive
      EHR programme, our multidisciplinary team designed an EHR-facilitated medication
      reconciliation programme by which pharmacy technicians engaged newly admitted
      patients and their caregivers at the bedside to develop and electronically
      document the BPMH. Strategy: Prior to this intervention, pharmacy technicians had
      no role in BPMH. Providers collected home medications documented on paper notes
      without a consistent methodology. With each plan-do-study-act (PDSA) cycle since
      the programme began, the goal was to increase the per cent of BPMH completed by a
      pharmacy technician. Individual PDSA cycles targeted either the pharmacy
      technicians by expanding their pool of eligible patients or provider engagement
      with the pharmacy technician workflow. Results: By optimising not only the health
      information technology platform but also the operational processes, the programme
      achieved a nearly 80% generation of BPMH completed by a highly trained pharmacy
      technician, surpassing its intended goal of 50% BPMH completion by a pharmacy
      technician on admission. Conclusion: An EHR-facilitated tool improved BPMH at an
      urban academic safety net hospital using pharmacy technicians.

PMID- 29450284
TI  - Reducing hospital admissions of healthy children with functional constipation: a
      quality initiative.
AB  - Functional constipation (FC) is a common medical problem in children, with
      minimal risk of long-term complications. We determined that a large number of
      children were being admitted to our children's hospital for FC in which there was
      no neurological or anatomical cause. Our hospital experienced a patient
      complication in which a patient died after inpatient treatment of FC.
      Subsequently, we developed a standardised approach to determine when paediatric
      patients needed hospitalisation for FC, as well as to develop a regimented
      outpatient therapeutic approach for such children to prevent hospitalisation. Our
      quality improvement initiative resulted in a large decrease in the number of
      children with FC admitted into the hospital as well as a decrease in the number
      of children needing faecal disimpaction in the operating room. Our quality
      improvement process can be used to decrease hospitalisations, decrease healthcare
      costs and improve patient care for paediatric FC.

PMID- 29450285
TI  - Reducing medical-surgical inpatient falls and injuries with videos, icons and
      alarms.
AB  - Background: Inpatient falls and subsequent injuries are among the most common
      hospital-acquired conditions with few effective prevention methods. Objective: To
      evaluate the effectiveness of patient education videos and fall prevention visual
      signalling icons when added to bed exit alarms in improving acutely hospitalised
      medical-surgical inpatient fall and injury rates. Design: Performance improvement
      study with historic control. Setting: Four medical-surgical units in one US
      public acute care hospital. Study participants: Adult medical-surgical inpatients
      units. Interventions: A 4 min video was shown to patients by trained volunteers.
      Icons of individual patient risk factors and interventions were placed at
      patients' bedsides. Beds with integrated three-mode sensitivity exit alarms were
      activated for confused patients at risk of falling. Main outcome measures: The
      main outcome measure is the incident rate per 1000 patient days (PDs) for patient
      falls, falls with any injury and falls with serious injury. The incident rate
      ratio (IRR) for each measure compared January 2009-September 2010 (baseline) with
      the follow-up period of January 2015-December 2015 (intervention). Results: Falls
      decreased 20% from 4.78 to 3.80 per 1000 PDs (IRR 0.80, 95% CI 0.66 to 0.96);
      falls with any injury decreased 40% from 1.01 to 0.61 per 1000 PDs (IRR 0.60, 95%
      CI 0.38 to 0.94); and falls with serious injury 85% from 0.159 to 0.023 per 1000
      PDs (IRR 0.15, 95% CI 0.01 to 0.85). Icons were not fully implemented.
      Conclusion: The first known significant reduction of falls, falls with injury and
      falls with serious injury among medical-surgical inpatients was achieved. Patient
      education and continued use of bed exit alarms were associated with large
      decreases in injury. Icons require further testing. Multicentre randomised
      controlled trials are needed to confirm the effectiveness of icons and video
      interventions and exit alarms.

PMID- 29450286
TI  - From research to practice: results of 7300 mortality retrospective case record
      reviews in four acute hospitals in the North-East of England.
AB  - Introduction: Monitoring hospital mortality using retrospective case record
      review (RCRR) is being adopted throughout the National Health Service (NHS) in
      England with publication of estimates of avoidable mortality beginning in 2017.
      We describe our experience of reviewing the care records of inpatients who died
      following admission to hospital in four acute hospital NHS Foundation Trusts in
      the North-East of England. Methods: RCRR of 7370 patients who died between
      January 2012 and December 2015. Cases were reviewed by consultant reviewers with
      support from other disciplines and graded in terms of quality of care and
      preventability of deaths. Results were compared with the estimates published in
      the Preventable Incidents, Survival and Mortality (PRISM) studies, which
      established the original method. Results: 34 patients (0.5%, 95% CI 0.3% to 0.6%)
      were judged to have a greater than 50% probability of death being preventable.
      1680 patients (22.3%, 95% CI 22.4% to 23.3%) were judged to have room for
      improvement in clinical, organisational (or both) aspects of care or less than
      satisfactory care. Conclusions: Reviews using clinicians within trusts produce
      lower estimates of preventable deaths than published results using external
      clinicians. More research is needed to understand the reasons for this, but as
      the requirement for NHS Trusts to publish estimates of preventable mortality is
      based on reviews by consultants working for those trusts, lower estimates of
      preventable mortality can be expected. Room for improvement in the quality of
      care is more common than preventability of death and so mortality reviews
      contribute to improvement activity although the outcome of care cannot be
      changed. RCRR conducted internally is a feasible mechanism for delivering
      quantitative analysis and in the future can provide qualitative insights relating
      to inhospital deaths.

PMID- 29450287
TI  - Reducing radiation hazard opportunities in neonatal unit: quality improvement in
      radiation safety practices.
AB  - Aim: Guided by the ALARA - "As Low As Reasonably Achievable" principle in
      radiation safety, a quality improvement project to optimise the bedside
      diagnostic imaging process to the best standards of care was conducted over a six
      month period. The goal was too reduce the radiation hazard opportunities in the
      neonatal intensive care unit by at least 75% from the existing level at Q2/2015,
      within 6 months. Methods: The existing bedside imaging process was critically
      analysed and the following quality improvement initiatives were implemented
      namely, mandatory lead protective gear to healthcare staff, gonadal shield for
      neonates, guidelines for optimal collimation of X-ray beam and optimal
      positioning of neonates. Radiation dosimetry results, regular staff awareness
      sessions and strong collaboration between neonatologists, radiologists,
      radiographers and neonatal nurses helped to ensure compliance to the revised
      imaging process. Radiation hazard opportunities were measured by analysing all
      radiographs done during the period under baby exposure and healthcare staff
      exposure categories. Summary of results: Radiation hazard opportunities were
      reduced by 100% to healthcare staff and 75% to neonates, and the overall
      reduction was 83%. The rate of discordance between radiograph request forms and
      images taken was measured as a surrogate marker for compliance to the project
      initiatives and it declined by 77%. Mandatory orientation of staff to the revised
      policy on the standardised diagnostic imaging process, regular radiation
      awareness talks and staff feedback sessions are among several measures taken to
      sustain the project.

PMID- 29450288
TI  - Improving care collaboration for NICU patients to decrease length of stay and
      readmission rate.
AB  - Background: Medically complex patients in neonatal intensive care units (NICUs)
      typically require long hospitalisations and care from multiple subspecialists.
      Scheduled multidisciplinary discussions could improve collaboration and
      continuity of care and thereby improve patient outcomes. The specific aims of the
      project were to decrease the average length of hospitalisation by at least 1 day
      and improve parent satisfaction ratings on a standard questionnaire by the end of
      our project's first year, and to maintain a stable (or decreased) cause-related
      (30-day) readmission rate. Methods: We designed a quality improvement project to
      enhance collaboration and continuity of care for medically complex infants cared
      for in the NICU of Brenner Children's Hospital. Weekly multidisciplinary team
      meetings were held to discuss the long-term plan for patients who met specific
      criteria. Attendees included attending neonatologists, paediatric surgeons, a
      physical therapist, an occupational therapist, a speech therapist, a social
      worker, a nurse coordinator for palliative care, a family support coordinator,
      the NICU Nurse Manager, a hospital chaplain, mid-level providers, bedside nurses,
      a nurse quality improvement leader and the leaders and database manager for the
      quality improvement project. When needed for specific patients, a bioethicist was
      included. Results: One year after implementing the project, the average duration
      of hospitalisation had decreased by 6.5 days. Cause-related readmission rates
      decreased from 3.33% to 0.95%. Parent satisfaction scores did not change
      significantly. Conclusions: Weekly multidisciplinary meetings to coordinate and
      provide continuity of care for medically complex neonates in our NICU was
      associated with improved patient outcomes.

PMID- 29450289
TI  - Improving combined contraceptive pill/oral contraceptives prescribing in general
      practice.
AB  - Introduction: Eighty per cent of contraceptive care occurs in the general
      practice setting. UK Medical Eligibility Criteria provides clear guidelines for
      the safe provision of appropriate contraception. The Faculty of Sexual and
      Reproductive Health and the National Institute for Health and Care Excellence
      offer further recommendations for initiation and continuation of the combined
      contraceptive pill/oral contraceptives. Method and analysis: Using the Egton
      Medical Information Systems database of an inner city, average size general
      practice we performed a retrospective analysis of combined contraceptive
      pill/oral contraceptives consultations to identify areas of substandard
      prescribing. Through three subsequent improvement cycles we demonstrated that the
      safety of combined contraceptive pill/oral contraceptives prescribing could be
      enhanced by consistent application of UK Medical Eligibility Criteria. By
      encouraging general practitioners to promote safe sex and use local long-acting
      reversible contraception options we were able to enhance the quality of
      consultations as dictated by national guidelines. Regular education and use of an
      amended EMIS template (to include UK Medical Eligibility Criteria) enabled us to
      improve both the safety and quality of community-combined contraceptive pill/oral
      contraceptives prescribing in a sustainable fashion.

PMID- 29450290
TI  - Improving the rates of electronic results acknowledgement at a tertiary eye care
      centre.
AB  - Background: Hundreds of thousands of tests are performed annually in hospitals
      worldwide. Safety Issues arise when abnormal results are not recognized promptly
      resulting in delayed treatment and increased morbidity and mortality. As a result
      Singapore's largest healthcare group, Singhealth introduced an electronic result
      acknowledgement system. This system was adopted by the Singapore National Eye
      Centre (SNEC) in February 2016. Baseline measurements show that weekly numbers of
      unacknowledged results ranged from 193 to 617. The current standards of
      electronic results acknowledgement posts a significant patient safety hazard.
      Methods: Root cause analysis was performed to identify contributory factors.
      Pareto principle was then used by the authors to identify the main contributory
      factors. We employed the rapid cycle improvement Plan-do-study-act (PDSA)
      strategy to test and evaluate implemented changes. Changes are implemented for 2
      weeks and data collected prospectively. The data is analyzed the week after and
      the following PDSA actions are decided and instituted the following week. 3 PDSA
      cycles were undertaken in total. Results: The first PDSA cycle focused on raising
      awareness of the problem at hand, the number of unacknowledged results
      drastically decreased during the 1stweek of implementation of our PDSA from 617
      to 254. The second PDSA cycle targeted the lack of knowledge of doctors involved
      in the electronic result acknowledgement process. There was a trend downwards
      near the end of the cycle which continued through the week after. The third PDSA
      cycle targeted individual doctors and provided individual remedial training.
      Second line doctors were also equipped to better handle abnormal results. There
      was significant improvement with the number of unacknowledged abnormal results
      dropping to <5 a week. Conclusions: Multiple factors were identified to
      contribute to the low compliance to electronic acknowledgement of results. The
      role doctors play in the issue at hand was paramount and required careful
      handling in a professional manner with multiple reminders and emphasis on the
      importance of acknowledging and acting on the results.A significant improvement
      in the rates of acknowledgement of abnormal results was demonstrated with clear
      benefits to patient safety. Interventions can be replicated when implementing
      similar systems to other areas of healthcare.

PMID- 29450291
TI  - The game of telephone: a sustained, low-cost, quality improvement initiative to
      enhance communication between patients and their resident physician.
AB  - This multidisciplinary quality improvement project was designed to enhance
      telephone communication between patients and their resident physician while
      concomitantly creating a standardised telephone communication protocol for
      resident internal medicine continuity clinics. The plan, do, study, act (PDSA)
      quality improvement framework model was applied for four distinct cycles.
      Baseline data were collected regarding open telephone encounters. The initial
      intervention entailed targeted communication to specific individual residents
      with open telephone encounters more than one SD above the average. The next cycle
      involved developing a novel communication process map that was distributed to
      faculty preceptors and clinic anchor nurses. The faculty preceptors then
      disseminated the new policies and communication algorithm to resident physicians.
      Finally, new resident and anchor nurses were educated about the standardised
      processes through scheduled orientation activities. After 19 months of
      implementation of this project with four PDSA cycles, resident open telephone
      encounters decreased by 40.7%. Resident telephone communication in continuity
      clinics can be improved through targeted individualised communication,
      implementation of a standardised telephone communication protocol, dissemination
      of communication algorithms to clinic faculty, residents and nurses and ongoing
      education to all parties through orientation activities to instil a self
      sustaining culture change.

PMID- 29450292
TI  - Using 'Active Signposting' to streamline general practitioner workload in two
      London-based practices.
AB  - General practice is at the forefront of the National Health Service, but is
      currently being overwhelmed by ever-increasing patient demand and financial
      constraints. Telephone consultations (TCs) have been used as a method to ease
      pressure on general practice. Many of these consultations are booked with general
      practioners (GPs), despite occasions when the patient could have either been
      signposted to self-help or offered an alternative service. This quality
      improvement project (QIP) aimed to evaluate the nature of TCs undertaken by GPs
      at our two practices; and whether the patients' needs could have adequately been
      met without the involvement of a GP. Consultations where this was the case were
      deemed 'possibly avoidable', and those where involvement with a GP was the best
      option have been termed 'essential'. A retrospective analysis was undertaken to
      establish a baseline figure for the proportion of possibly avoidable TCs in two
      practices. A new intervention was then introduced, with reception staff following
      a set of protocols when booking in patients. Patients who did not require a GP to
      deal with their query were actively signposted by reception staff to other allied
      healthcare professionals, non-medical staff or an alternative service at the time
      of booking their appointment. Two practices were involved in the study. After 2
      Plan, Do, Study, Act (PDSA) cycles, the proportion of essential consultations
      taking place at both practices increased from 28.6% and 27.3% at baseline, to
      82.6% and 71.4%, respectively. A lower number of possibly avoidable TCs equates
      to more time for essential TCs and greater value for money for the practice.
      Patient access to care is also improved, with patients directed to alternative
      and often quicker services which still meet their needs adequately. With the
      current system of primary care unable to cope with the demands it faces,
      interventions such as active signposting provide value for both GP practices and
      patients alike.

PMID- 29450293
TI  - Right service, right place: optimising utilisation of a community nursing service
      to reduce planned re-presentations to the emergency department.
AB  - Background: Congruent with international rising emergency department (ED) demand,
      a focus on strategies and services to reduce burden on EDs and improve patient
      outcomes is necessary. Planned re-presentations of non-urgent patients at a
      regional Australian hospital exceeded 1200 visits during the 2013-2014 financial
      year. Planned re-presentations perpetuate demand and signify a lack of
      alternative services for non-urgent patients. The Community Nursing Enhanced
      Connections Service (CoNECS) collaboratively evolved between acute care and
      community services in 2014 to reduce planned ED re-presentations. Objective: This
      study aimed to investigate the evolution and impact of a community nursing
      service to reduce planned re-presentations to a regional Australian ED and
      identify enablers and barriers to interventionist effectiveness. Methods: A mixed
      methods approach evaluated the impact of CoNECS. Data from hospital databases
      including measured numbers of planned ED re-presentations by month, time of day,
      age, gender and reason were used to calculate referral rates to CoNECS. These
      results informed two semistructured focus groups with ED and community nurses.
      The researchers used a theoretical lens, 'diffusion of innovation', to understand
      how this service could inform future interventions. Results: Analyses showed that
      annual ED planned re-presentations decreased by 43% (527 presentations) after
      implementation. Three themes emerged from the focus groups. These were right
      service at the right time, nursing uncertainty and system disconnect and medical
      disengagement. Conclusions: CoNECS reduced overall ED planned re-presentations
      and was sustained longer than many complex service-level interventions. Factors
      supporting the service were endorsement from senior administration and strong
      leadership to drive responsive quality improvement strategies. This study
      identified a promising alternative service outside the ED, highlighting
      possibilities for other hospital emergency services aiming to reduce planned re
      presentations.

PMID- 29450294
TI  - Improvement in patient and physician notification of cardiac rhythm device report
      transmissions.
AB  - Background Cardiac rhythm devices (CRD) require complex management to identify
      potential device or patient issues. While easy to obtain, report processing is
      complex and time consuming. In our population, a majority of reports were
      performed outside of institutional protocols and no method for electrophysiology
      (EP) notification for unscheduled reports existed. These process breakdowns led
      to potential issues with safety and associated loss of work efficiency. Objective
      Our aim was to decrease the percentage of reports without EP notification from
      30% to 10% over a 9-month time period. Methods We created a detailed process map
      of in-office and home device reporting. Failure mode and effects analysis
      (FMEA)/Pareto charts were used to determine the mechanistic underpinnings of
      notification failures and identify areas for process improvement. Multiple
      interventions were implemented using the Plan-Do-Study-Act (PDSA) technique.
      Process run charts and control charts were used to evaluate ongoing changes.
      Results Our FMEA identified failures related to (1) lack of physician
      understanding of the device reporting system, (2) lack of an easy to use method
      of EP notification and (3) lack of patient understanding of report notification.
      Pareto charts identified the most frequent failures to be associated with
      specific cardiology subspecialties as well as reports sent from home. We
      performed multiple interventions including(1) creation of an easy to use method
      of EP notification used by patients and medical staff, (2) physician education
      and (3) patient education. Compared with baseline reporting, there was a decrease
      from 30% to <10% of device reports obtained without EP notification. This process
      improvement additionally resulted in a 34% reduction in time required for device
      processing. Conclusions Development of a unified EP reporting system and quality
      improvement methodology resulted in improved CRD report notification and improved
      efficiency for staff. These process changes resulted in improvement across
      differing cardiac subspecialty providers and patients.

PMID- 29450295
TI  - Reducing patient mortality, length of stay and readmissions through machine
      learning-based sepsis prediction in the emergency department, intensive care unit
      and hospital floor units.
AB  - Introduction: Sepsis management is a challenge for hospitals nationwide, as
      severe sepsis carries high mortality rates and costs the US healthcare system
      billions of dollars each year. It has been shown that early intervention for
      patients with severe sepsis and septic shock is associated with higher rates of
      survival. The Cape Regional Medical Center (CRMC) aimed to improve sepsis-related
      patient outcomes through a revised sepsis management approach. Methods: In
      collaboration with Dascena, CRMC formed a quality improvement team to implement a
      machine learning-based sepsis prediction algorithm to identify patients with
      sepsis earlier. Previously, CRMC assessed all patients for sepsis using twice
      daily systemic inflammatory response syndrome screenings, but desired
      improvements. The quality improvement team worked to implement a machine learning
      based algorithm, collect and incorporate feedback, and tailor the system to
      current hospital workflow. Results: Relative to the pre-implementation period,
      the post-implementation period sepsis-related in-hospital mortality rate
      decreased by 60.24%, sepsis-related hospital length of stay decreased by 9.55%
      and sepsis-related 30-day readmission rate decreased by 50.14%. Conclusion: The
      machine learning-based sepsis prediction algorithm improved patient outcomes at
      CRMC.

PMID- 29450296
TI  - Reducing bed occupancy and length of stay on a functional older adults'
      psychiatric ward.
AB  - A quality improvement project was initiated on Ivory ward, a functional older
      adult psychiatric inpatient ward at Newham Centre for Mental Health, part of the
      East London NHS Foundation Trust. The project was started by staff on the ward
      after it had come to their attention that their ward had the highest bed
      occupancy and length of stay across similar wards in the trust. The mean bed
      occupancy in the 9 months before the project started was 87.7%. The mean length
      of stay on the ward in the 9 months before the project started was 70 days. The
      team used the model for improvement, which is the trust's methodology of choice
      for quality improvement projects, to reduce bed occupancy and length of stay. The
      focus was on running small-scale tests of change to see whether these could lead
      to improvement. These change ideas were refined, scaled up or discontinued as
      appropriate to help achieve the aim. The project's aim was to promote quality of
      care by reducing patient length of stay on Ivory ward to 45 days and bed
      occupancy to <=70% or by 1 January 2016. The project team managed to reduce bed
      occupancy to 58% and length of stay to an average of 35 days.

PMID- 29450297
TI  - Improving venous thromboembolism risk assessment rates in a tertiary urology
      department.
AB  - Venous thromboembolism (VTE) is a significant cause of mortality and morbidity
      among hospitalised patients. A VTE risk assessment reduces this through
      facilitating correct prophylaxis. Since 2010, the Commissioning for Quality and
      Innovation payments framework dictates that >95% adult inpatients must have a VTE
      risk assessment within 24 hours of admission. This target is not currently being
      met by the urology department at Guy's and St. Thomas' Trust (GSTT). Following
      analysis, a quality improvement project aimed to increase VTE risk assessment
      rates for patients admitted under urology at GSTT. Two series of interventions
      were introduced following the Plan, Do, Study, Act structure aimed at urology
      theatres and wards, respectively. These boosted awareness of the VTE risk
      assessment and streamlined it into routine surgical workload. Despite not
      reaching the 95% target, the project increased rates among patients admitted
      directly to surgical units by 5%-8%. It highlighted the difficulties in driving a
      change in established routine and demonstrated a need for firmer interventions
      with effective communication.

PMID- 29450298
TI  - Improving transitions of care: a resident-driven approach to address delays in
      patient care during the direct admission process.
AB  - Background: The direct admission process is a complex system that can be
      aggravated by inherent gaps in communication leading to inefficient continuity of
      care and patient safety issues. Bypassing the emergency room, triage is often
      associated with long periods of unmonitored observation and significant delays in
      patient assessment. We identified significant communication gaps, delays in
      placement of admission orders and patient assessment during the direct admission
      process at our institution. To address this issue, we created and implemented a
      standardised direct admission flow diagram that consists of a step-by- step
      direct admission process, which includes a communication device and a triage
      power plan in the Electronic Medical Record. Methods: We used the Plan-Do-Study
      Act (PDSA) model for Quality improvement to address communication gaps in the
      direct admission process Baseline measurement confirmed two critical gaps in
      communication: 1) communication to the Medical Admitting Resident (MAR), the
      central source of communication of all medicine admissions, and 2) delays in
      placement of orders and assessment of the patient. Results: Two months after
      implementation of a standardised process that addressed the two major gaps in
      communication, we found that communication to the MAR increased from 16% (7/42)
      to 100% (15/15). Additionally, the average time for order placement and
      assessment of patient decreased from 153 minutes to 53 minutes (n=15).
      Conclusion: In order to improve the safety of direct admissions, the entire
      process must be carefully analysed and potential delays in patient assessment
      should be minimised. A standardised flow diagram that identified and targeted
      specific communication gaps can minimise delays in patient care.

PMID- 29450299
TI  - Reducing hypothermia in newborns admitted to a neonatal care unit in a large
      academic hospital in New Delhi, India.
AB  - Neonatal hypothermia is a common and dangerous condition around the world. 70% of
      neonates born in Kalawati Saran Children's Hospital in New Delhi, India, and
      subsequently admitted to the neonatal intensive care unit (NICU) had a
      temperature below 36.5 degrees C on admission. In July 2016, we formed a team of
      staff from the labour room, NICU and auxiliary staff to reduce hypothermia in
      babies transported to our NICU using quality improvement methods. We identified
      problems related to staff awareness of hypothermia and its dangers, environmental
      factors and supply issues in the labour room, and challenges with rapidly and
      safely transferring sick newborns to the NICU. We used the Plan-Do-Study-Act
      cycles to test and adapt solutions to these problems. Because infection is a
      common complication of hypothermia, we also instituted a training programme to
      improve handwashing skills among parents and health workers. Within 9 months of
      starting our quality improvement project, the proportion of neonates who were
      normothermic on admission increased from 27% to 75%, the number of cases of late
      onset neonatal sepsis decreased from 15.2 to 5 cases/1000 patient days, and all
      cause mortality fell from 4.2 to 2.6 neonatal deaths per week. Multiple factors
      can lead to neonatal hypothermia, and the most important factors will differ from
      facility to facility. Quality improvement methods provide health workers with the
      skills to identify the key factors contributing to hypothermia in their facility
      and to develop strategies to address them. Addressing processes of care can lead
      to improved thermal care and save lives.

PMID- 29450300
TI  - Optimisation of intravenous fluid prescribing: framework for changing practice
      through education and audits.
AB  - Introduction: Intravenous fluids are one of the most commonly prescribed drugs in
      the hospital setting and yet the practice continues to fall short of National
      Institute for Health and Care Excellence (NICE) guidelines, with significant gaps
      in staff knowledge exposing patients to heightened morbidity and mortality. Aim:
      Following the 2013 publishing of updated NICE guidelines on intravenous fluid
      prescribing, an intravenous fluid team was formed within the Royal Liverpool
      University Hospital (RLUH). Their role has been (and continues to be) to overhaul
      the culture of suboptimal intravenous fluid prescribing within the hospital and,
      ultimately, to improve patient outcomes. A framework to engender this change has
      been developed and is offered as an example to other Trusts within which
      improvement of guideline-compliant intravenous fluid prescribing remains
      stagnant. Method: There have been three principal stages of the project to this
      point which are best demonstrated in a chronological manner. The period of 2010
      2014 allowed for assessment of the issue of intravenous fluid prescribing and
      analysis of its causes through serial audits and a staff-wide survey. From 2015,
      there has been implementation of several measures (educative, managerial,
      administrative and technological) within the hospital to foster reproducible and
      positive change with regards to intravenous fluid prescribing. Finally, between
      2016 and 2017, three cycles of a rolling audit based on NICE guidelines have been
      completed to allow measurement of improvement in intravenous fluid prescribing
      practice. Conclusion: Results have demonstrated a significant improvement in the
      appropriateness of the intravenous maintenance and replacement fluids prescribed
      in the hospital since the March 2016 audit. Moreover, a 29-fold increase has been
      observed in the use of 4% dextrose/0.18% sodium chloride as maintenance fluid
      (gold standard as per NICE guidelines) since the staff-wide survey of 2015.
      Despite progress however, adherence to NICE guidelines remains below the
      recommended 100% and therefore further work remains to be done.

PMID- 29450301
TI  - Preventing cerebral palsy in preterm labour: a multiorganisational quality
      improvement approach to the adoption and spread of magnesium sulphate for
      neuroprotection.
AB  - Magnesium sulphate has been demonstrated to be an effective neuroprotectant for
      babies delivered prematurely (under 37 weeks' gestational age). Antenatal
      administration reduces infant mortality and cerebral palsy (CP); however, uptake
      in the UK has been significantly lower than other countries. A quality
      improvement (QI) project (PReventing Cerebral palsy in Pre Term labour (PReCePT))
      was carried out in the West of England, UK, to raise awareness of evidence and to
      improve the uptake of magnesium sulphate as neuroprotectant in preterm
      deliveries. Five National Health Service (NHS) Trusts and the West of England
      Academic Health Science Network participated in the QI project. The project was
      underpinned by a multifaceted QI approach that included: patient and clinical
      coproduction of resources; recruitment of clinical champions to support the local
      microsystems and create a stimulating/supporting environment for change; Plan,
      Do, Study, Act cycles; training for over 600 NHS staff and awareness raising and
      strategic influencing of key leaders. A baseline audit and regular measurement of
      the number of eligible women receiving magnesium sulphate was undertaken at each
      hospital site, and the overall programme was evaluated using data from an
      international benchmarking organisation for neonatal care outcomes-the Vermont
      Oxford Network. During the project 664 staff received magnesium sulphate
      training. The use of magnesium sulphate increased across the West of England from
      an average baseline of 21% over the 2 years preceding the project to 88% by the
      conclusion of the project. The project was also able to influence the development
      of a national data collection process for benchmarking the use of magnesium
      sulphate for neuroprotection in preterm deliveries in the U.K. PReCePT appears to
      have had a favourable effect on the uptake of magnesium sulphate across the West
      of England. The project has also provided learning about how to stimulate
      adoption and spread of evidence using a QI approach across a network.

PMID- 29450302
TI  - How Kabarole Hospital in western Uganda saved mothers' lives through team-based
      problem-solving.

PMID- 29450303
TI  - Monitoring long-term oral corticosteroids.
AB  - Corticosteroids are synthetic analogues of human hormones normally produced by
      the adrenal cortex. They have both glucocorticoid and mineralocorticoid
      properties. The glucocortoid components are anti-inflammatory, immunosuppressive,
      anti-proliferative and vasoconstrictive. They influence the metabolism of
      carbohydrate and protein, in addition to playing a key role in the body's stress
      response. Mineralocorticoid's main significance is in the balance of salt and
      water concentrations. Due to the combination of these effects, corticosteroids
      can cause many adverse effects. Oral corticosteroids are absorbed systemically
      and are therefore more likely to cause adverse effects than topical or inhaled
      corticosteroids. Furthermore, it is assumed that greater duration of treatment
      will lead to a greater number of adverse effects, and therefore the most at risk
      group are those taking high dose, long-term oral corticosteroids (LTOC). High
      dose is defined as a prescription of >5 mg oral prednisolone and long term as
      duration of treatment >1 month (based on National Institute for Health and Care
      Excellence guidance for patient's 'at risk' of systemic side effects). Parameters
      to be monitored in primary care include weight, blood pressure, triglycerides,
      glucose and urea and electrolytes. From clinical experience within the general
      practice setting, the authors propose that these patients do not receive adequate
      baseline monitoring before starting corticosteroids nor are these markers
      monitored consistently thereafter. This project intended to evidence this claim,
      evaluate the adverse effect profile and improve monitoring in this patient group.
      The initial audit of 22 patients, within a single general practice, detected at
      least one documented adverse effect in 64% of patients, while 41% reported more
      than one adverse effect. 45% had recorded weight gain, 18% had recorded
      osteoporosis, 18% had at least one recorded cataract, 14% had recorded
      Hypertension, 14% had recorded diabetes mellitus, 9% had recorded dyspepsia and
      5% had a recorded psychiatric complaint. All of these recorded conditions were
      either directly attributed to steroid medication or occurred since LTOC were
      prescribed. The aim of this project was to increase the percentage of patients on
      LTOC with complete baseline monitoring to 100%. 'Baseline monitoring' was defined
      as a measurement taken within the previous 5 years. Although somewhat arbitrary,
      5 years was felt to be the maximum timeframe in which monitoring would still be
      relevant for comparison following introduction of LTOC. Quality improvement
      methodology was used throughout this project with multiple PDSA (Plan, Study, Do
      and Act) cycles. Through this, a monitoring system and protocol for patients
      taking LTOC was developed. As a result of this project, five adverse effects were
      detected in five different patients. These included two cases of secondary
      hypertension, one case of diabetes mellitus, one cataract and one case of adrenal
      insufficiency. 12 out of 20 patients achieved complete baseline monitoring. While
      this study did not fully achieve its aim, the aim was deliberately ambitious. As
      not all patients in this study attended for monitoring, a figure of 100% was
      impossible to achieve. The remaining 'incompletely monitored patients' had some
      but not all parameters measured. The creation of a staff protocol and increased
      clinical experience will ensure that complete monitoring takes place in the
      future. In conclusion, this project has shown that adverse effects from LTOC are
      prevalent in a single general practice population. It is also shown that
      monitoring for LTOC adverse effects is inadequate but can be improved relatively
      easily as skills and competencies from other medication monitoring systems
      already exist within healthcare settings and are immediately transferable.

PMID- 29450304
TI  - Use of audit, feedback and education increased guideline implementation in a
      multidisciplinary stroke unit.
AB  - Background: The audit-feedback cycle is a behaviour change intervention used to
      reduce evidence-practice gaps. In this study, repeat audits, feedback, education
      and training were used to change practice and increase compliance with Australian
      guideline recommendations for stroke rehabilitation. Objective: To increase the
      proportion of patients with stroke receiving best practice screening, assessment
      and treatment. Methods: A before-and-after study design was used. Data were
      collected from medical records (n=15 files per audit). Four audits were conducted
      between 2009 and 2013. Consecutive files of patients with stroke admitted to the
      stroke unit were selected and audited retrospectively. Staff behaviour change
      interventions included four cycles of audit feedback, and education to assist
      staff with change. The primary outcome measure was the proportion of eligible
      patients receiving best practice against target behaviours, based on audit data.
      Results: Between the first and fourth audit (2009 and 2013), 20 of the 27 areas
      targeted (74%) met or exceeded the minimum target of 10% change. Practice areas
      that showed the most change included sensation screening (+75%) and
      rehabilitation (+100%); neglect screening (+92%) and assessment (100%). Some
      target behaviours showed a drop in compliance such as anxiety and depression
      screening (-27%) or little or no overall improvement such as patient education
      about stroke (6% change). Conclusions: Audit feedback and education increased the
      proportion of inpatients with stroke receiving best practice rehabilitation in
      some, but not all practice areas. An ongoing process of quality improvement is
      needed to help sustain these improvements.

PMID- 29450305
TI  - The grimace scale reliably assesses chronic pain in a rodent model of trigeminal
      neuropathic pain.
AB  - The limited success in translating basic science findings into effective pain
      management therapies reflects, in part, the difficulty in reliably assessing pain
      in experimental animals. This shortcoming is particularly acute in the field of
      chronic, ongoing pain. Quantitative analysis of facial expressions-the grimace
      score-was introduced as a promising tool, however, it is thought to reliably
      assess only pain of short or medium duration (minutes to hours). Here, we test
      the hypothesis that grimace scores are a reliable metric of ongoing neuropathic
      pain, by testing the prediction that chronic constriction injury of the
      infraorbital nerve (CCI-ION) will evoke significant increases in grimace scale
      scores. Mice and rats were subjected to CCI-ION, and tested for changes in
      mechanical hypersensitivity and in grimace scores, 10 or more days after surgery.
      Both rats and mice with CCIION had significantly higher grimace scores, and
      significantly lower thresholds for withdrawal from mechanical stimuli applied to
      the face, compared to sham-operated animals. Fentanyl reversed the changes in rat
      grimace scale scores, suggesting that these scores reflect pain perception. These
      findings validate the grimace scale as a reliable and sensitive metric for the
      assessment of ongoing pain in a rodent model of chronic, trigeminal neuropathic
      pain.

PMID- 29450306
TI  - Editorial.

PMID- 29450307
TI  - Editorial.

PMID- 29450308
TI  - EDITORIAL.

PMID- 29450309
TI  - Old and new in exploring the anterior chamber angle.
AB  - Angle-closure glaucoma includes a number of entities with closed angle, elevated
      intraocular pressure, in association with optic nerve damage and visual field
      defects as common markers. These entities are characterized by irido-trabecular
      apposition, irido-trabecular synechiae or both. The angle configuration must be
      systematically checked at least one time in patients presenting with raised
      intraocular pressure or glaucoma. Gonioscopy represented for a long time the gold
      standard for clinically assessing anterior chamber angle structures and their
      configuration. However, the interpretation of gonio-scopic findings is subjective
      and only semiquantitative. With the development of new imaging techniques of the
      anterior segment, new analysis methods have also emerged. Ultrabiomicroscopy was
      the first method of analyzing the anterior segment and is still the only imaging
      technique for all anterior segment structures (especially the ciliary body).
      Another method is optical coherence tomography, a non-contact technique by which
      angle configuration can be assessed in a more rapid and less invasive manner.
      Recently developed Pentacam technology could represent in the near future a more
      quantitative, rapid and non-invasive screening tool which could allow early
      detection of angle closure glaucoma and narrow angle configurations by measuring
      a set of anterior chamber parameters. List of abbreviations: ACG -angle closure
      glaucoma, ASOCT-anterior segment optical coherence tomography UMB- ultrasound
      biomicroscopy (ultrabiomicroscopy), PAS-posterior angle synechiae ACD-anterior
      chamber depth, ACV-anterior chamber volume, PLI-periphery laser iridotomy.

PMID- 29450310
TI  - The influence of optical aberrations in refractive surgery.
AB  - Optical aberrations lead to defects in image-forming, the image obtained being
      imperfect and thereby decreasing the quality of vision. When an optic system is
      not perfect, as happens with the eye, the rays of light that pass through the
      system produce optical aberrations. The purpose of this review is to describe
      optical aberrations and their impact on vision and how refractive surgery
      outcomes are influenced by them. The main optical aberrations of the eye are as
      follows: spherical aberration, chromatic aberration, oblique astigmatism and high
      order aberrations. When the patient undergoes various types of surgeries
      (cataract surgery, corneal refractive surgery) the properties of the eye change
      and the eye doctor must take into account the correction of optical aberrations
      to improve vision quality. Abbreviations: LASIK (laser in situ keratomileusis),
      PRK (photorefractive keratectomy), UDVA (uncorrected distance visual acuity), SA
      (spherical aberrations), HOA (higher-order aberrations), RMS (root mean square).

PMID- 29450311
TI  - National centers of excellence in glaucoma.
AB  - Glaucoma refers to a group of related eye disorders that have in common an optic
      neuropathy associated with visual function loss. It is the second leading cause
      of blindness in developed countries and Romania and the first cause of
      irreversible blindness worldwide. In Europe, 2% of the population over 40 and 7%
      of the population over 80 have glaucoma. In Romania, there are no official
      statistics concerning glaucoma disease, but it was estimated that over 160000
      Romanians suffer from this disease and only 50% of them are undergoing treatment.
      The silent evolution of the disease, the deficient sanitary education, the lack
      of well structured national programs for screening and follow-up and the lack of
      adherence to treatment and check-ups, are the causes of late diagnosis and
      irreversible visual function loss. The article emphasizes the need for national
      centers specialized in managing patients with glaucoma, from prevention,
      screening, early diagnosis to treatment and monitoring.

PMID- 29450312
TI  - Retrocorneal membranes after penetrating keratoplasty.
AB  - Purpose. To present a rare complication after penetrating keratoplasty. Methods.
      The review presents the main types of retrocorneal membranes. The incidence,
      pathophysiology, diagnosis and treatment are shown for all of them. Conclusions.
      The evaluation and management of a membrane behind the posterior surface of the
      cornea is a special challenge for ophthalmologists. The clearer understanding of
      the pathogenesis of the different types of retrocorneal membranes may allow a
      more specific and efficient treatment.

PMID- 29450314
TI  - Intraoperative and postoperative complications in trabeculectomy, Clinical study.
AB  - Glaucoma represents a progresive multifactorial optic neuropathy characterised by
      retinal ganglion cell loss and atrophy of the optic nerve its main cause being
      high intraocular pressure. [1,2] Trabeculectomy is the most used surgical method
      when it comes to the majority of the ophthalmologists which is why knowing and
      managing the intraoperative and postoperative complications well is very
      important. [3] Objective/aim.The study aims to establish the success rate and to
      evaluate the intraoperative and postoperative complications in a group of 75
      patients with glaucoma 1 year after surgery. Methods. A retrospective study was
      made on a group of 75 adult patients with different types of glaucoma which were
      refractory to medical treatment, for whom the treatment option was the
      trabeculectomy surgical intervention . Results and discussions. The success rate
      measured 1 year after the surgery was of 89%.The most complications were found in
      patients with open angle glaucoma, neovascular glaucoma and glaucoma secondary to
      vitreo-retinal surgery. Trabeculectomy is a surgical procedure associated with
      numerous complications, so much so that the follow-up and the management of the
      aforementioned complications are sometimes more laborious than the surgery
      itself.

PMID- 29450313
TI  - Anti-vascular endothelial growth factor indications in ocular disease.
AB  - The purpose of this systemic review was to investigate the indications of anti
      vascular endothelial growth factor (anti-VEGF) in the treatment of ocular
      diseases. For this, a comprehensive literature research was performed exploring
      the current use of anti-VEGF in a variety of retinal or anterior segment diseases
      and highlighting the visual outcome for these patients. The anti-VEGF therapy is
      now commonly used for a wide range of pathologies like age-related macular
      degeneration, retinal vein occlusion or diabetic retinopathy. Pathological
      processes such as abnormal neovascularization, ocular angiogenesis and macular
      edema which can greatly reduce visual acuity are now targeted by anti-VEGF
      treatment, having a major impact on vision.

PMID- 29450315
TI  - Partial results after treatment of diabetic macular edema with Bevacizumab.
AB  - Purpose: To present the morphological and functional results after treating
      diabetic macular edema with Bevacizumab. Patient and method: It is a prospective
      trial which includes 15 patients with diabetic macular edema (proved by OCT and
      fluorescein angiography examination). The inclusion criteria are: central retinal
      thickness over 250 um, visual acuity of the studied eye between 0.1 and 0.5,
      absence of a previous treatment. We excluded patients with macular edema caused
      by other ethiology or with any other macular disease. Every patient was treated
      with 3 intravitreal injections with Bevacizumab at every 6 weeks; we analyzed the
      results after 4 months. Results: The mean visual acuity improved from 0.33 +/-
      0.06 at baseline to 0.49 +/- 0.13 at 4 months (or from 31+/-3.9 ETDRS letters to
      39+/-5.67 letters). The central retinal thickness decreased from 457 +/- 174 um
      to 338 +/- 139 um. There was also an improvement of retinal sensibility on the
      microperimetry map. Conclusions: The treatment of diabetic macular edema produced
      an increase of visual acuity and a decrease of macular thickness after the first
      3 injections with Avastin, but it is necessary to monitor the patients to detect
      the rebound of the edema and to initiate retreatment.

PMID- 29450316
TI  - Corneal hysteresis and primary open angle glaucoma.
AB  - Objects: To investigate the variability of the corneal hysteresis in primary open
      angle glaucoma(POAG) patients. Material and Methods: Out of 123 eyes, 99 carried
      out the inclusion criteria and were investigated further using Goldman
      Aplanotonometer to measure intraocular pressure(IOP), Ocular Response
      Analyzer(ORA) in order to determine corneal hysteresis (CH) and corneal
      resistance factor(CRF), ultrasonic pachimetry (Ocuscan) to measure central
      corneal thickness(CCT) and Humphrey visual field to determine mean deviation(MD),
      pattern standard deviation(PSD) and visual field index(VFI). The patients were
      divided into two groups: one group of diagnosed POAG patients and one control
      group of healthy individuals. Statistical analysis was performed using
      descriptive analyses and linear regression. Results: A considerable statistic
      correlation was found between CH and VFI both in the group of primary open angle
      glaucoma patients(r=0.52, P<0.0001), and the control group (r=0.22, p<0.04).
      Conclusions: The study shows a positive correlation, statistically significant,
      between corneal hysteresis and visual field index both in glaucoma patients and
      control subjects proving that a lower CH associates with a lower VFI. Ocular
      response analyzer can be considered a useful instrument in evaluation of primary
      open angle glaucoma patients.

PMID- 29450317
TI  - Complications of combined retinal and retinal pigment epithelium hamartoma
      involving the optic disc in a child, treated with Avastin - a review of the
      literature and case presentation.
AB  - We present a case of a 9 years old boy, followed up for 4 years, with bilateral
      combined pigmented epithelial and retinal hamartoma, complicated with recurrent
      vitreous hemorrhages in one eye and neovascular glaucoma and cataract in the
      other eye, treated with repeated intravitreal injections of Bevacizumab. A review
      of the literature suggested that such lesions may be symptomatic because of
      decreased vision, macular pucker, strabismus and vitreous hemorrhages. This
      particular compressive, bilateral form of hamartoma of the optic nerve has not
      previously been reported as a cause for such an ischemic syndrome, complicated
      with neovascular glaucoma and cataract.

PMID- 29450318
TI  - Ophthalmological implications of the chronic infections with the hepatitis C
      Virus.
AB  - Objectives. Report of a clinical case reuniting the dry eye syndrome in a severe
      form, the Mooren's ulcer and necrotizing anterior scleritis with inflammation,
      with bilateral affectation in the context of chronic infection with the hepatitis
      C virus. Methods. A female patient aged 66 diagnosed with chronic hepatitis with
      HCV, with ophthalmological antecedents of Mooren's ulcer and severe form of dry
      eye syndrome in both eyes, comes to the emergency unit with hypopyon corneal
      ulcer in the right eye, shortly afterwards developing necrotizing anterior
      scleritis with inflammation. The patient is administered treatment for chronic
      hepatitis C, following which the ARN-HCV viremia decreases without ocular
      exacerbations. When the viremia level increases again, two lesions indicating
      necrotizing anterior scleritis are observed in the left eye. The evolution is
      favourable with topical and systemic treatment with corticosteroids. Complicated
      cataract is surgically treated in the right eye and vitreous humour is collected
      during surgery. Results. Visual acuity increases in the right eye after the
      surgery, while antibodies-HCV are identified in the vitreous humour. Conclusions.
      Chronic infection with hepatitis C virus displays multiple extra-hepatic
      manifestations and the ophthalmological ones require a multidisciplinary approach
      from both the chronic diseases practitioner and the ophthalmologist.

PMID- 29450319
TI  - Upper eyelid abscess as a late complication of frontal sinus trauma.
AB  - The authors report a case of upper eyelid abscess in a 30 year old male that
      presented in the ophthalmology department with complains of recurrent eyelid
      pyosis, hyperaemia and swelling that started 2 months earlier and that did not
      ease to repeated courses of antibiotic therapy. The reported history of the
      patient revealed frontal sinus trauma that occurred 5 years before and that
      required surgical treatment (fixation with titan plaque and screws) with total
      healing and giving no further complains over the next years. The present cranial
      CT imaging showed intraorbital fat infiltration with displacement of one orbital
      arcade screw. Clinical findings showed normal ocular mobility. Antibiotic
      treatment and screw extraction through eyelid fistula improved the outcome but
      did not resolve the fistulous communication. Final management involved surgical
      removal of orbital arcade plaque and remaining screw and excision of fistula
      tract. The postoperative outcome was very good and the fistula remained closed
      but left the patient with an upper eyelid retraction which will require
      oculoplastic surgery in the future.

PMID- 29450320
TI  - Total retinal detachment occurring after minor head trauma.
AB  - The objective of this article is to present the case of a patient with a severe
      decrease of visual acuity that occurred after an apparently minor head injury.
      Following the investigations, the patient was diagnosed with rhegmatogenous
      retinal detachment that was triggered by a fall from the same level and which
      occurred on a background of lattice degeneration. In this case, a minor trauma
      caused a severe complication because the patient had a contributing factor for
      the complication. The patient was operated and the end result was satisfactory.

PMID- 29450321
TI  - Editorial.

PMID- 29450322
TI  - Editorial.

PMID- 29450323
TI  - Age related strabismus.
AB  - Age related binocular vision disorders (age related strabismus) could include all
      types of spontaneous strabismus appearing along the lifetime, which are directly
      connected with the aging process. Neurological strabismus is excluded. Functional
      and structural changes related to the aging process can induce phoria
      decompensation, convergence insufficiency decompensation and new onset strabismus
      as distance esotropia or vertical strabismus induced by the sagging eye syndrome.
      MRI studies sustain the hypothesis of age related structural changes of
      extraocular muscles pulleys and their influence on the eye position and motility
      nominated as sagging eye. Age Related Distance Esotropia, Age Related Divergence
      Insufficiency Esotropia are probably different names for the same type of
      strabismus. All types of age related binocular disorders require treatment
      because of the accompanying diplopia. Prisms or/ and surgery can improve the
      patients' life quality by eliminating diplopia in primary position and main
      gazes.

PMID- 29450324
TI  - Chromovitrectomy.
AB  - The term "chromovitrectomy" has been coined to define the use of vital dyes in
      vitreoretinal surgery. The basic concept for the application of vital dyes during
      vitreoretinal surgery is to assist in highlighting preretinal membranes and
      tissues which are very thin and semitransparent and thus difficult to detect.
      Various dyes are currently being used in routine clinical procedures, however,
      the ideal staining agent has not yet been found. The vital dyes indocyanine
      green, infracyanine green, and brilliant blue stain the internal limiting
      membrane, trypan blue and triamcinolone acetonide help to visualize the
      epiretinal and vitreous membranes. New dyes with a better safety profile than the
      synthetic ones are important for optimizing the outcome of modern ophthalmic
      surgery and natural dyes, such as lutein, offer a potentially safer and more
      efficient method of identifying intraocular structures such as vitreous and ILM.
      Any dye, which is intravitreally injected has the potential to become toxic.

PMID- 29450325
TI  - New perspectives in retinal imaging - angio OCT.
AB  - In the last few years, structural and functional optical coherence tomography
      (OCT) technology has seen new and revolutionary developments. The most important
      of all is OCT angiography (Angio-OCT). Angio-OCT already plays an important role
      in clinical ophthalmology as a new, non invasive and dyeless diagnostic tool,
      which serves as an adjunct to, or even a replacement for fluorescein and
      indocyanine green (ICG) angiographies. Angio-OCT brings multiple technical and
      clinical improvements in the study of retinal diseases, glaucoma, and optic nerve
      disorders. It enables rapid, high-resolution, detailed images of large retinal
      vessels and capillary networks in seconds by using a strategy called "motion
      contrast", as opposed to revealing detailed images of large retinal vessels and
      capillary networks in seconds by using a strategy called "motion contrast" as
      opposed to the minutes required in conventional fluorescein angiography. These
      images are uniquely three-dimensional and allow an isolated study of individual
      capillary beds at different depths of the retina.

PMID- 29450326
TI  - Implication of gelatinases in retinoblastoma development.
AB  - The aim of this paper was to reveal the latest clinical and research findings
      regarding the implications of MMP2 and MMP9 matrix metalloproteinases in
      retinoblastoma development. The targets were finding better options for the
      therapeutic approach, considering the etiopathogeny and biology of this tumor.

PMID- 29450327
TI  - Common causes of red eye presenting in northern Iran.
AB  - AIM: This study aimed to determine the causes of red eye disease among patients
      of Mazandaran-Northern Iran. METHODS: This cross sectional study included 840
      patients who referred to eye clinics with ocular complaints. A detailed history
      of patients was recorded and their eyes were examined. Then, pre designed
      checklists were completed by the researcher. RESULTS: The most common cause of
      red eye was conjunctivitis - 30% (252/ 840), foreign bodies 23.2%, trauma
      including penetrating or blunt 8.6%, respectively. There was a significant
      relationship between the red eye trauma, with acute onset and duration of less
      than a week (P=<0.0001). Diagnoses of red eye were conjunctivitis in 31.3% of the
      cases separately, viral causes (19.5%), allergic (7%) and bacterial (4%), foreign
      bodies 22.9%, pterygium 7%, and trauma 6.5%, respectively. CONCLUSION: In the
      current study, the most common causes of red eyes were conjunctivitis, foreign
      bodies, and trauma respectively. Red eye was more common in males than in
      females. An appropriate and proper training of risky factors of red eyes in the
      future could reduce the risk of serious visual problems.

PMID- 29450328
TI  - Diagnosis of non-exudative (DRY) age related macular degeneration by non-invasive
      photon-correlation spectroscopy.
AB  - PURPOSE: Photon-correlation spectroscopy (PCS) (quasi-elastic light scattering
      spectroscopy, dynamic light scattering spectroscopy) allows the non-invasively
      reveal of local dynamics and local heterogeneities of macromolecular systems. The
      capability of this technique to diagnose the retinal pathologies by in-vivo
      investigations of spatial anomalies of retinas displaying non-exudative senile
      macular degeneration was evaluated. Further, the potential use of the technique
      for the diagnosis of the macular degeneration was analyzed and displayed by the
      Receiver Operating Curve (ROC). METHODS: The maculae and the peripheral retina of
      73 normal eyes and of 26 eyes afflicted by an early stage of non-exudative senile
      macular degeneration were characterized by time-correlation functions and
      analyzed in terms of characteristic decay times and apparent size distributions.
      RESULTS: The characteristics of the obtained time-correlation functions of the
      eyes afflicted with nonexudative macular degeneration and of normal eyes differed
      significantly, which could be referred to a significant change of the nano- and
      microstructure of the investigated pathologic maculas. CONCLUSIONS: Photon
      correlation spectroscopy is able to assess the macromolecular and microstructural
      aberrations in the macula afflicted by non-exudative, senile macular
      degeneration. It has been demonstrated that macromolecules of this disease show a
      characteristic abnormal behavior in the macula.

PMID- 29450329
TI  - "Off-label" use of intravitreal bevacizumab in non-ischemic macular edema
      secondary to retinal vein obstructions.
AB  - OBJECTIVE: To evaluate the safety and efficacy of intravitreal Bevacizumab in
      treatment of non-ischemic macular edema secondary to retinal vein obstruction
      (RVO). MATERIALS AND METHODS: A 2-year-retrospective study was performed on 26
      patients hospitalized for non-ischemic macular edema secondary to RVO. All the
      patients underwent a complete ophthalmologic exam, with best corrected visual
      acuity (BCVA) testing, fundus photography, fluorescein angiography (FA) and
      macular thickness measurement by optical coherence tomography (OCT). Reevaluation
      was performed monthly for VA, OCT, and ophthalmoscopy and, at every 3 months, by
      FA. A standard protocol of 0.05 ml intravitreal Bevacizumab injection was
      applied. Further administrations were performed according to clinical evolution.
      RESULTS: The medium follow-up period was of 9,7 months (6-20 months). There were
      no significant complications following the procedure. The number of intravitreal
      Bevacizumab injections varied from 2-5/ patient. All the patients experienced an
      improvement in VA and a significant regression of macular edema. The smallest
      number of intravitreal Bevacizumab injections and the best visual prognosis were
      observed in cases with branch retinal vein obstruction (BRVO) and early
      presentation (p<0.05). CONCLUSIONS: As a pathogenic therapy, intravitreal
      Bevacizumab is a safe, repeatable procedure and it may be considered an effective
      and lasting treatment for non-ischemic macular edema secondary to RVO.
      Intravitreal Bevacizumab should be included in the therapeutic protocol of RVO,
      both for early and delayed presentations. Abbreviations: RVO = retinal vein
      obstruction, BRVO = branch retinal vein obstruction, CRVO = central retinal
      branch obstruction, BCVA = best corrected visual acuity, FA = fluorescein
      angiography, OCT = optical coherence tomography.

PMID- 29450330
TI  - Aflibercept efficacy in refractory choroidal neovascularization.
AB  - : The aim of the report is to evaluate the short-term efficacy and safety of
      aflibercept (EYLEA(r)) in patients with choroidal neovascularization (CNV)
      transformed into refractory during treatment with bevacizumab (AVASTIN (r)).
      METHODS: Clinical, morphological, and functional changes were retrospectively
      evaluated in cases with refractory CNVs to monthly 1.25 mg bevacizumab
      intravitreal injections (AVASTIN (r)) and switched to 3 monthly 2.0 mg
      intravitreal injections of aflibercept (EYLEA (r)). RESULTS: In this pilot
      evaluation, 8 cases of CNVs that become refractory to intravitreal treatment with
      1.25 mg intravitreal bevacizumab (AVASTIN (r)), were switched to 2.0 mg
      intravitreal aflibercept (EYLEA (r)) and evaluated. The mean age of patients was
      67.6 years (54-74 years). In 7 cases, CNV was associated to age related macular
      degeneration and in 1 case to angioid streaks. The mean number of previous
      intravitreal bevacizumab (AVASTIN(r)) administrations was 9.32 (7-12). In all
      cases, the last 3 intravitreal injections of bevacizumab were performed at an
      interval of maximum 6 weeks. The refractory status was confirmed by the lack of
      improvement or worsening of the clinical features as revealed by SD-OCT. A slowly
      anatomical improvement was noticed in 5 out of 8 cases (62.5%) since the first
      aflibercept administration. The anatomical improvement was stable after 3 monthly
      administrations. During the treatment, only 3 out of 5 cases (60%) showing
      anatomical improvement had a minor visual benefit (one line of VA gain). In 3
      cases, the treatment change was unremarkable. No side effects were noticed.
      CONCLUSIONS: The anatomical improvement confirms previous reports regarding the
      efficacy and safety of aflibercept (EYLEA(r)) in some cases of CNV that became
      refractory during conventional anti-VEGF therapy. The improvement can be, at
      least partially, explained by the more complex features of aflibercept.
      Unfortunately, a minor visual benefit was noticed in a limited number of cases.

PMID- 29450331
TI  - Can patients with visual impairment follow a normal school?
AB  - AIM: To highlight the needs for socio-professional orientation of patients with
      visual impairment. MATERIAL AND METHODS: Prospective observational study on 69
      patients (47 boys and 22 girls), with a mean age of 15,99+/-3,4235 years,
      evaluated in the Ophthalmology Clinic of "Sf. Spiridon" Hospital Iasi, in order
      to obtain a medical certificate. Clinical parameters: slit lamp examination,
      fundoscopy, visual acuity, intraocular pressure, orthoptic exam, ocular
      ultrasound, or corneal pachymetry (in selected cases). A questionnaire for the
      age group of 12-18 years was applied. Data were statistically analyzed by using
      the Student's t-test. RESULTS: Sixteen patients had ocular prosthesis or visual
      acuity 0 in one eye and 31 patients had a low vision. Patient's diagnosis:
      anterior segment diseases (23,18%), posterior segment diseases (52,17%), other
      diagnoses (24,63%). The pathology was congenital in 60,86% of the cases. 13,04%
      of the patients (3 school children and 6 students) asked for the integration into
      normal school/ university. Frequent answers: lack of special means of assistance
      in schools/ universities, need for additional schooling, people's reluctance
      which led to situations of ridicule, dependence on others to perform daily
      activities, need for professional help. CONCLUSIONS: Children with eye
      deficiencies can be scholarized in normal an educational system, according to the
      level of intelligence. Adolescents with eye disorders may attend University
      courses if proper aids are provided. Socio-professional orientation should be
      performed as early as possible to increase the quality of life in sighted
      patients. Aids for low-vision patients are insufficiently used in Romania.

PMID- 29450332
TI  - Corneal endothelial morphology and function after torsional and longitudinal
      ultrasound mode phacoemulsification.
AB  - PURPOSE: To study the endothelial cell morphology and corneal thickness changes
      after phacoemulsification by using the OZil torsional and longitudinal ultrasound
      techniques (Infiniti Vision System, Alcon Laboratories). SETTING: Department of
      Ophthalmology, Clinical Center, University of Debrecen, Debrecen, Hungary.
      METHODS: 52 patients with cataract were randomly assigned to longitudinal
      ultrasound and torsional mode group. All surgeries were performed through a 2.2
      mm clear corneal incision, the method employed being divide and conquer. The
      endothelial morphometry such as cell density (ECD), mean cell area, coefficient
      of variation of cell area, and central corneal thickness were examined with
      specular microscopy (EM-1000, Tomey) preoperatively and 4, 8 weeks
      postoperatively. RESULTS: ECD values decreased significantly in both surgical
      groups (P < .001, repeated- mesures ANOVA), the postoperative endothelial cell
      loss was higher in the longitudinal ultrasound mode group (3.5% and 6.5%, at 4
      and 8 weeks after surgery) than in the torsional group (3.3% and 5.5%, at 4 and 8
      weeks after surgery), the difference not being significant between the two groups
      (P = .164 and P = .479, at 4 and 8 weeks after surgery, Mann-Whitney test). There
      was no statistically significant difference in any of the assessed parameters
      between the two surgical groups (P > .05). No significant correlation was found
      between the endothelial cell loss and the nucleus density. CONCLUSIONS: Both
      phacoemulsification techniques were safe and effective. The torsional handpiece
      performs oscillatory movements and delivers less energy into the eye than the
      longitudinal ultrasound technique, therefore providing more favorable energy and
      thermal safety profile.

PMID- 29450333
TI  - Finite element analysis on a medical implant.
AB  - Several studies have shown a tight connection between several ocular pathologies
      and an increased risk of hip fractures due to falling, especially among elderly
      patients. The total replacement of the hip joint is a major surgical intervention
      that aims to restore the function of the affected hip by various factors, such as
      arthritis, injures, and others. A corkscrew-like femoral stem was designed in
      order to preserve the bone stock and to prevent the occurrence of iatrogenic
      fractures during the hammering of the implant. In this paper, the finite element
      analysis for the proposed design was applied, considering different loads and
      three types of materials. A finite element analysis is a powerful tool to
      simulate, optimize, design, and select suitable materials for new medical
      implants. The results showed that the best scenario was for Ti6Al4V alloy,
      although Ti and 316L stainless steel had a reasonable high safety factor.

PMID- 29450334
TI  - Central retinal vein occlusion in a young adult Case report.
AB  - PURPOSE: To report the case of a 48-year-old man with unilateral central retinal
      vein occlusion. METHODS: The clinical, hematologic and hypercoagulability
      evaluations of the patient were thoroughly and specifically carried out. RESULTS:
      The central retinal vein occlusion was of nonischemic type and was associated
      with polyglobulia, hyperleukocytosis, hypercholesterolemia, multiple dental foci,
      and pulmonary sequelae of tuberculosis. CONCLUSIONS: When a patient less than 50
      years of age experiences central retinal vein occlusion, other mechanisms, such
      as the hyperviscosity syndrome or the inflammatory condition (inflammation of the
      central retinal vein) should be specifically considered and accounted for.

PMID- 29450335
TI  - Secondary open-angle pigmentary glaucoma resulting from pseudophakia. Case
      report.
AB  - PURPOSE: To report the case of a 60-year-old man with a pseudophakia-related
      secondary open-angle pigmentary glaucoma without individual hereditary steroid
      susceptibility. METHODS: The clinical and functional evaluations of the patient
      were thoroughly and specifically carried out. RESULTS: The unilateral
      pseudophakic open-angle pigmentary glaucoma occurred in the context of rubbing of
      the haptics and optic of a posterior chamber intraocular lens implanted in the
      sulcus, against the posterior surface of the iris, with resultant pigment
      dispersion, trabecular inflammation, and aqueous outflow obstruction.
      CONCLUSIONS: Although the clinical picture of our case was very similar to that
      of pigmentary glaucoma, the distinction between the two conditions was still
      quite easy, considering that pigmentary glaucoma is a bilateral disorder
      predominantly affecting young myopic men with Krukenberg spindle and increased
      incidence of steroid responsiveness.

PMID- 29450336
TI  - Continuous efforts to increase the visibility of Romanian Journal of
      Ophthalmology.

PMID- 29450337
TI  - Computer assisted design and finite element analysis of contact lenses.
AB  - Contact lenses are an attractive alternative for vision corrections. Their
      improvement can be achieved by optimizing the geometry, use of new materials, and
      application of high precision processing technologies. The optimized design can
      be obtained by computer-aided design, considering the principles of geometrical
      optics. Inventor Professional and other similar advanced 3D CAD software allows
      complex approaches, selection of suitable materials with better mechanical/
      optical properties. This is useful for the preparation of the virtual design for
      3D printing or CNC fabrication. A finite element analysis is also of interest for
      testing the best design/ material choice. In this paper, the finite element
      analysis for a tri-curve contact lens was applied. The selected materials were
      PMMA and polycarbonate. The applied compressive loads were in the range from 10
      to 100MPa. Our results showed that the best scenario was for the polycarbonate,
      but PMMA also had a high safety factor. The maximum compression load with a
      reasonable safety factor (of 7-9 depending on materials) was 12MPa.

PMID- 29450338
TI  - Small eye - a small stump which can challenge and tilt a great surgery.
AB  - The small eye suggests an apparently robust anatomy with a more resistant sclera,
      good trabecular function, good uvea trophicity, a healthy retina, with a full
      papilla. The volume of these eyes is small. Usually, the volume of the eye is
      related to the sagittal diameter of the eye. However, the volume of a sphere
      varies with the third power of the radius of the sphere. These small eyes have a
      volume smaller than their sagittal diameter suggests. In this volume, highly
      decreased develop certain anatomical components without having to keep
      proportions (lens, choroid), and some have a continuous growing volume (lens). On
      long term, there is a balance inside these eyes despite a disproportion between
      their components. This internal disproportion inside the small eye can erupt
      through pressure differences between its structures: pupillary block, angle
      closure or a disproportionate response in case of typically uncomplicated
      surgery, which alters the apparent internal balance of these eyes. Seemingly
      simple surgeries, such as phacoemulsification or filtering surgery can trigger
      storm (storms occur by differences in atmospheric pressure) with the following
      characteristics: - intraocular "precipitation" in the form of uveal effusions,
      massive choroidal hemorrhage exudative retinal detachment, CME - breaks in
      anatomical barriers, lens posterior capsular tear - deviations courses: aqueous
      misdirection Surgical operations on these eyes are like a dangerous storm
      surfing, with risks, incidents, with unpredictable but great experience and
      courage request.

PMID- 29450339
TI  - Bevacizumab in the treatment of acute central/hemicentral retinal vein
      occlusions.
AB  - Even if bevacizumab is unlicensed, a majority of retina specialists still
      currently recommends it in retinal vein occlusion-related macular edema. For the
      first time, the results of our studies showed evidence suggesting that an early
      treatment administered immediately after the onset of venous occlusion, provided
      a significant and sustained improvement in visual acuity and foveal thickness,
      with inactive disease (dry retina and stable visual acuity for at least 6 months
      after the last injection) in most phakic patients with acute central/ hemicentral
      retinal vein occlusions, making this treatment option a rational and viable
      therapeutic strategy. Central/ hemicentral retinal vein occlusion has to be
      considered an ophthalmic emergency. The highlighting of the ocular conditions
      most frequently associated with central/ hemicentral retinal vein occlusion
      (ocular hypertension, primary open angle glaucoma, primary angle closure suspect,
      primary angle closure, and primary angle closure glaucoma) is mandatory.
      Regardless of the anti-vascular endothelial growth factor agents used
      (bevacizumab/ ranibizumab / aflibercept/), and regardless of the treatment
      approaches chosen (treat-and-extend/ pro re nata algorithm), the efficacy of
      therapy depends primarily on the precociousness of the therapy after the
      diagnosis of central/ hemicentral retinal vein occlusion. Any delay in the
      treatment will adversely influence the restoration of visual functions, which are
      difficult to correct even with subsequent treatment.

PMID- 29450340
TI  - Ocular surface - a complex and vulnerable adoptive environment for topical
      glaucoma treatment.
AB  - Ocular surface is a complex functional unit in which tissues so different as
      structure and function harmonize to produce a very short life (15-45 sec) film -
      tear film essential for the quality of the vision. With age, the ocular surface
      undergoes a physiological decline, often with a limitation of its functionality.
      Administration of topical glaucoma treatment itself constitutes a solicitation of
      the ocular surface and the nature of "accessories" included in this "drop
      glaucoma treatment", that might be the last straw which breaks the fragile
      balance or aggravates a previously nonexistent suffering subclinical
      symptomatology by opening and inducing reactions to treatment. Topical treatment
      in glaucoma could have the complex aspect of an adoption. Every adoption is a
      delicate and unpredictable phenomenon. Success does mean harmony and coexistence.
      For the adoption to succeed, one needs to know well the adoptive environment, the
      adopted element and the science and art to harmonize them together.

PMID- 29450341
TI  - Translating data and measurements from stratus to cirrus OCT in glaucoma patients
      and healthy subjects.
AB  - Aim: our study tried to find a mathematical conversion method of the measurements
      obtained in Time Domain (TD) OCT to Spectral Domain (SD) OCT. Material and
      method: A prospective randomized, double blind study that included 244 eyes, from
      121 patients (normal subjects, glaucoma suspects, glaucoma), in whom we analyzed
      the retinal nerve fiber layer (RNFL) and the optic disc in the same session by
      using TD OCT (Stratus) and SD OCT (Cirrus), was performed. The means for RNFL
      thickness (overall value and per quadrants), neural area and cup/ disc (C/ D)
      ratio, were measured. Results: We found statistically significant differences
      between parameters measured in TD OCT and SD OCT (p<0.001). Powerful correlations
      were calculated between parameters measured with the two OCT machines. Data
      dispersion showed a linear relation between measurements. One can use the
      following mathematical equations for conversion: Mean RNFL (Cirrus) = 15.77 +
      0.748 x Mean RNFL (Stratus) Mean neural area (Cirrus) = 0.508 + 0.388 x Mean
      neural area (Stratus) Mean C/ D ratio (Cirrus) = 0.157 + 0.792 x Mean C/ D
      (Stratus) Conclusions: data based on our calculated mathematical conversion
      equations can be converted into SD OCT. Therefore, we offered a useful tool for
      the long term monitoring of our patients although the initial measurements in TD
      OCT made comparisons for patients later measured with SD OCT impossible.
      Abbreviations: RNFL = retinal nerve fiber layer, TD OCT = time domain optical
      coherence tomography, SD OCT = spectral domain optical coherence tomography, VF =
      visual field, CI = confidence interval, ISNT segments = inferior, superior,
      nasal, temporal segment.

PMID- 29450342
TI  - Epidemiology of ocular emergencies in Cluj ophthalmology clinic.
AB  - Objective. This study focused on the epidemiology of ocular diseases in the Eye
      Emergency Room. Methods. A cross-section retrospective study was performed in the
      Ophthalmology Clinic in Cluj-Napoca and included 11786 patients who presented to
      the Eye Emergency Room throughout the whole year, from January to December.
      Results. Every month, between 782 to 1189 patients with an average age of 39.54
      years (+/-21.14) presented to the Eye Emergency Room. 250 were infants, under 1
      year old. Six disease categories were followed: inflammation, trauma, vascular,
      tumor, glaucoma, and retinal-vitreal. Conjunctivitis and corneal foreign bodies
      accounted for almost half of the cases. Most of the conjunctival cultures
      revealed negative results. Conclusions. Consistent with the large number of
      patients included in this study, we considered the epidemiological data
      representative for our region. Male gender and youth represented the main risk
      factor for eye injury, while children remained the main group with
      conjunctivitis.

PMID- 29450343
TI  - Conjunctival autograft in pterygium treatment.
AB  - Pterygium is characterized by the thickening of the bulbar conjunctiva and the
      invasion of the cornea from the sclerocorneal limbus to the central portion of
      the cornea. Pterygium produces corneal deformation, which extends toward the
      central portion of the cornea. The visual disorders depend on the corneal extent.
      The treatment goal is the removal of the corneal and conjunctival portion of the
      pterygium and the coverage of the resulting conjunctival defect. The association
      of the pterygium surgical excision was assessed with conjunctival autograft. For
      this purpose, a retrospective study was performed on 68 patients and was extended
      over 7 years (2009-2015). Patients with recurrent pterygium were excluded. The
      time for corneal re-epithelization and for the pain and photophobia disappearance
      was followed. The incidence of recurrence was also observed. Pain levels were
      assessed by using a 10-point visual analog linear scale (VAS). The mean time for
      ocular pain and photophobia disappearance was of 48 hours. The mean pain score
      was 3.38 at 24 hours after surgery. Corneal re-epithelialization was achieved in
      60 hours after surgery. Recurrence occurred in 6 patients. It was concluded that
      pterygium surgical excision with conjunctival autograft is effective in pterygium
      surgery.

PMID- 29450344
TI  - Risk factors and long term progression in open angle glaucoma patients.
AB  - Aim: Investigation of perimetric progression rate and associated risk factors in
      open angle glaucoma, in clinical practice. Methods: Retrospective study based on
      clinical charts reviews of patients with primary open angle glaucoma (POAG) being
      followed for > 5 years with >/ = 5 SITA Standard visual fields. Demographics,
      visual acuity (VA), central corneal thickness (CCT), intraocular pressure (IOP)
      and IOP variation, treatment (number of medications), visual fields and
      associated systemic pathologies were recorded. Patients were followed at every 3
      6 months, when identical tests were performed. VF progression rate was calculated
      as slope of mean deviation (MD) over time by Glaucoma Progression Analysis
      software. Results: 121 eyes of 121 patients with POAG were included in the study
      and were followed for a mean period of 68.81 months (SD +/ - 31.7). The mean MD
      at start was -3.55 dB (SD +/ -5.19)., with a mean number of VF tests of 9.3+/ 
      2.9. Progression rate reached -0.21 +/ -0.1 db/ year. Mean IOP of all visits
      decreased over time from 18.20 mmHg to 16.53 mmHg (p<0.05). Systemic factors like
      positive history of hypertension reached statistical relevance in terms of
      increased risk for glaucoma progression, but only after age and sex were
      corrected. MD slope was explained in ANOVA univariate analysis, by the level of
      MD at baseline, IOP baseline, number of topical medications and CCT in a
      proportion equal to 71.7% (p=0.004). Conclusion: Rate of visual field changes in
      POAG was correlated and dependent on the baseline MD level, IOP at baseline,
      number of topical medications and a thin CCT.

PMID- 29450345
TI  - Vogt-Koyanagi-Harada syndrome Case report.
AB  - Vogt-Koyanagi-Harada syndrome is an uncommon multisystem inflammatory disorder
      characterized by panuveitis with serous retinal detachment and is often
      associated with neurologic and cutaneous manifestations including headache,
      hearing loss, vitiligo, and poliosis. The case of a 62-year-old female with
      diabetes mellitus and a history of primary open angle glaucoma (POAG) in both
      eyes, operated on the left eye two weeks prior to the presentation and under
      topical antiglaucomatous drops, was reported. She presented at the
      ophthalmological service for decreased visual acuity (VA) in both eyes. The slit
      lamp examination revealed keratic precipitates and posterior iris synechiae in
      both eyes and an ExPress aqueous shunt in the left eye. Inferior retinal
      detachment was observed on ocular fundus examination on both eyes. Intraocular
      pressure value was in normal range under antiglaucomatous drops (dorzolamid +
      timolol). The distinctiveness of this case was the association of the VKH
      syndrome with POAG and the inability to prolong the corticosteroid treatment,
      necessary in this case, due to the association of diabetes mellitus.

PMID- 29450346
TI  - Fulminant bilateral acute retinal necrosis after chickenpox - a case report.
AB  - : We present the case of a 34-year-old male, admitted for progressive bilateral
      loss of vision after a recent episode of chickenpox. Ophthalmological exam
      revealed bilateral acute retinal necrosis. As the patient was following a drug
      detoxification program, he was tested for HIV, HVB, HVC, and results highly
      positive. Immediate intravenous therapy with high doses of acyclovir and
      methylprednisolone was initiated, but the evolution was extremely severe
      resulting in necrotic retinal detachment. Surgery was performed in right eye, but
      no improvement of visual acuity was observed. CONCLUSIONS: The fulminant
      evolution of bilateral acute retinal necrosis and the lack of response to maximal
      intravenous therapy were clinical elements indicating coexistent
      immunosuppressive disease. Very severe acute retinal necrosis may occur in
      immunosuppressed patients, leading to blindness.

PMID- 29450347
TI  - Combined etiology for bilateral and simultaneous optic neuropathy in a patient
      with ciancobalamin deficit and hepatitis C treated with peg-interferon and
      ribavirin.
AB  - We report the case of a 53-year-old female patient who developed bilateral sudden
      visual acuity loss after 15 weeks from the initiation of Peg-Interferon and
      Ribavirin treatment for hepatitis C. Debut was simultaneous and asymmetric,
      reported in the morning, at awakening. No pain or other symptom was reported by
      the patient. Results. At presentation, visual acuity was 0.2 in RE and 3/ 50 in
      LE. Pupillary reflexes were sluggish and severe dyschromatopsia was documented in
      both eyes (Ishihara plates). Fundus examination revealed bilateral pale optic
      disc edema, more prominent in LE, with splinter hemorrhages in the RNFL around
      the optic disk. Visual field exam demonstrated severe defects in 3 quadrants of
      the RE, whereas in the LE, it was impossible to perform the investigation due to
      VA<0.1. Neurologic evaluation was normal; other possible causes of systemic
      vasculitis were excluded by negative lab tests. Acute inflammatory markers
      (fibrinogen and ESR) and mild pancytopenia were the only documented laboratory
      changes in this patient. Anamnesis cleared the traditional risk factors for
      conventional AION (hypertension, diabetes, ischemic heart disease, and
      hypercholesterolemia). Cranial and orbital CT scan and MRI findings were normal.
      Patient was withdrawn from the Interferon and Ribavirin treatment and was
      administered methyl prednisolone pulse therapy (1g/ day) for 3 days, continued
      with oral Prednisone (60 mg/ day) tapered slowly for over 12 weeks. VA increased
      to 0.8 during treatment in the RE, but visual recovery in the LE was not as
      spectacular (0.16) as in the fellow eye. Modified latencies and amplitudes in
      evoked visual potentials examination during 4 months time emphasized bilateral
      optic atrophy. Optic nerve sufferance was amplified by a low level of vitamin
      B12, detected by chance at the last eye visit. Due to the general condition,
      dietary supplementation was not possible. Conclusion. A case of a patient with
      bilateral and simultaneous NAION caused by IFN and Ribavirin treatment for
      hepatitis C, who was also vitamin B12 deficient, was analyzed. Therefore, a
      combined etiology for optic atrophy was explained.

PMID- 29450348
TI  - An atypical case of post surgery macular edema -Case report.
AB  - The article presents an atypical case of bilateral postoperative macular edema,
      with an unfavorable outcome, however considering the treatment options and ways
      to prevent this complication.

PMID- 29450349
TI  - Atopic keratoconjunctivitis with corneal ulcer. Case report.
AB  - Purpose: To report the case of a 14-year-old male patient, with bilateral atopic
      keratoconjunctivitis with corneal ulcer. Methods: The patient complained of
      bilateral red, itchy eyes, decreased vision, photophobia, difficulty opening the
      eyelids upon awakening, palpebral edema, excessive tearing, along with yellowish
      mucous discharge. He had a two-year history of chronic blepharitis and recurrent
      episodes of conjunctivitis that were treated with Tobramycin and corticosteroid
      eye drops over the years. The patient's past medical history was significant for
      atopic dermatitis (AD) and he had a family history for atopy. At the eye exam:
      his best-corrected visual acuity at the initial presentation was 0.2 in the right
      eye and 1.0 in the left eye. The following elements were found upon the slit lamp
      biomicroscopy: Eyelids - +4 palpebral edema (pseudoptosis), Dennie-Morgan fold
      and Herthoge's sign were both present, tylosis; Conjunctiva - hyperaemia,
      cobblestone appearance of the tarsal papillae in both eyes, +2 chemosis; Cornea -
      corneal edema with a 8 mm * 4 mm epithelial defect in the inferior part of the
      cornea, covered partially by the lied, that stained positive with fluorescein
      dyes. Using the Evaluation Signs Severity for Allergic Ocular Diseases, a
      diagnosis of bilateral atopic keratoconjunctivitis with a grade 3 status for the
      right eye and a grade 2 status, was made. It was decided that he should be
      administered Olopatadine hydrochloride and Sodium cromoglicate eye drops, along
      with Moxifloxacin and steroid eye drops. The microbiological exam tested positive
      for staphylococcus aureus, and, based on the sensitivity pattern, Chloramphenicol
      eye drops had to be added to the treatment. After 2 weeks, his symptoms
      diminished, pain was significantly relieved and inflammation was markedly
      reduced, but the corneal ulcer persisted. In order to prevent corneal
      perforations, amniotic membrane transplantation (AMT) was used to promote
      epithelialization. Results: A month later, the epithelial defect healed smoothly
      in an underlying vascular stromal scar and the visual acuity improved to 0.4 RE.
      Conclusions: This case demonstrated the role of patient history and close
      clinical obser-vation in the diagnosis of AKC. As this case showed, the use of
      topic medication along with amniotic membrane transplantation (AMT) was
      successful in the treatment of atopic keratoconjunctivitis and secondary
      staphylococcal aureus keratitis.

PMID- 29450350
TI  - Romania - UEMS, EBO.

PMID- 29450351
TI  - Glaucoma after chemical burns and radiation.
AB  - Glaucoma after chemical burns represents a posttraumatic glaucoma, usually open
      angle glaucoma. It is a frequent complication of chemical burns, especially with
      alkali and it can appear in the acute stage or as a late complication. Because of
      the complications and scars, the treatment is very difficult. Topical treatment
      is based on AC inhibitors, beta-blockers, alpha2-agonists. Trabeculectomy,
      shunts, cyclophotocoagulation, and cryotherapy are the solutions in the late
      stages. Glaucoma after irradiation is a closing-angle secondary glaucoma. The
      risk factors such as the radiation dose and the volume of the radiated structure
      are important in the appearance and evolution of this type of glaucoma. Topical
      treatment is usually ineffective, the preferable options being laser and surgical
      treatments. Although it is not a frequently seen pathology, it is important to
      know how to diagnose and treat this type of glaucoma. There are various options
      available for treatment, but choosing one is difficult because of the possible
      complications.

PMID- 29450352
TI  - Ethical issues in advertising and promotion of medical units.
AB  - Bioethics tries to define the medical activity and any other related activity
      needed to maintain the function of a health institution, through the development
      of principles and moral values. Bioethics is quite broad and has a background
      that combines various disciplines such as medicine, philosophy, law, sociology,
      and theology. Advertising and promotion are part of the strategy aimed at
      developing and maintaining relationships with the targeted audience (patients).
      To regulate this activity, it was necessary to develop ethical rules of
      healthcare marketing. The content of promotional messages must be truthful and
      should not create unjustified expectations. The doctor or the healthcare unit
      must be able to provide the services claimed in the advertisement. From an
      ethical point of view, marketing communication should be more consistent with
      reality, even if its purpose is to shed light on more attractive issues. In this
      context, the categories and groups vulnerable to certain content of the
      advertising message should be mentioned. A patient with a serious suffering will
      be easily influenced and will tend to trust any promise easily, with the desire
      to heal. Ethically, the information presented must not alter the reality and
      should not give false hopes to patients. Those responsible for marketing in the
      healthcare field must keep in mind the ethics code of the medical profession,
      must maintain an honest marketing communication, which does not create inaccurate
      expectations, must not denigrate other colleagues, and must use a message whose
      content should respect the dignity of the profession.

PMID- 29450354
TI  - Subliminal perception of complex visual stimuli.
AB  - Rationale: Unconscious perception of various sensory modalities is an active
      subject of research though its function and effect on behavior is uncertain.
      Objective: The present study tried to assess if unconscious visual perception
      could occur with more complex visual stimuli than previously utilized. Methods
      and Results: Videos containing slideshows of indifferent complex images with
      interspersed frames of interest of various durations were presented to 24 healthy
      volunteers. The perception of the stimulus was evaluated with a forced-choice
      questionnaire while awareness was quantified by self-assessment with a modified
      awareness scale annexed to each question with 4 categories of awareness. At
      values of 16.66 ms of stimulus duration, conscious awareness was not possible and
      answers regarding the stimulus were random. At 50 ms, nonrandom answers were
      coupled with no self-reported awareness suggesting unconscious perception of the
      stimulus. At larger durations of stimulus presentation, significantly correct
      answers were coupled with a certain conscious awareness. Discussion: At values of
      50 ms, unconscious perception is possible even with complex visual stimuli.
      Further studies are recommended with a focus on a range of interest of stimulus
      duration between 50 to 16.66 ms.

PMID- 29450353
TI  - The importance of assessing corneal biomechanical properties in glaucoma patients
      care - a review.
AB  - Purpose: to familiarize the public with the role of corneal biomechanics in
      glaucoma patient management. Methods: Ocular Response Analyzer (ORA) is the only
      device that measures in vivo corneal biomechanics. Recent studies regarding
      "corneal biomechanics and glaucoma" were reviewed and the obtained data were
      compared in order to present a better understanding of the corneal biomechanical
      properties involvement in glaucoma care. Results: According to the studies
      reviewed, in primary open angle glaucoma (POAG) the mean corneal hysteresis (CH)
      and the corneal resistance factor (CRF) were approximately 2 mmHg lower than in
      normal eyes. In ocular hypertension (OH), the mean CH was about 1mmHg higher than
      in POAG patients and 1mmHg lower than in the control group, while the mean CRF
      was about 2mmHg higher than in POAG and 1mmHg higher than in the control group.
      Regarding the normal tension glaucoma (NTG), there were studies that showed that
      the mean CH and CRF were approximately 1mmHg lower than in POAG and studies that
      showed similar values between the POAG and NTG groups. The mean CH did not differ
      much between POAG and angle closure glaucoma (ACG), being lower than in normal
      individuals, while CRF appeared to be higher in the ACG than in normal
      individuals. Concerning congenital glaucoma (CG), both CH and CRF were about
      2mmHg lower than in normal eyes. Conclusions: Corneal biomechanics influenced the
      IOP measurement and have been proven to be of a great significance in glaucoma
      patients regardless of the central corneal thickness (CCT). Lower values of CH
      and CRF could suggest an alteration in the corneal response associated to
      glaucoma.

PMID- 29450355
TI  - Survey on retrobulbar blood flow in glaucomatous optic neuropathy (normotensive
      and hypertensive).
AB  - The aim of this study was to analyze the possible differences between retrobulbar
      blood flows in normotensive glaucomatous optic neuropathy patients versus
      patients with hypertensive glaucomatous optic neuropathy, with intraocular
      pressure controlled treatment. All the patients in the study group were subjected
      to a color Doppler echography of retrobulbar vessels. Afterwards, systolic and
      diastolic blood velocities were measured in both eyes in ophthalmic artery (OA),
      central retinal artery (CRA) and posterior ciliary arteries (PCA). The device
      calculated the Resistivity index Pourcelot (RI) automatically.

PMID- 29450356
TI  - Color Doppler imaging of the retrobulbar circulation in progressive glaucoma
      optic neuropathy.
AB  - It is known that elevated intraocular pressure (IOP) is the primary risk factor
      for glaucoma. Recently, more and more evidences have shown that the vascular
      deficit also plays an important role in the pathogenesis and progressions of
      glaucomatous optic neuropathy. This issue is backed up by glaucomatous optic
      neuropathy (GON) cases drug compensated in which the progression of the disease
      in one or both eyes is ascertained despite a normal and relatively constant IOP.
      The present study evaluated the hemodynamic parameters in the retrobulbar
      circulation in patients with progressive glaucomatous optic neuropathy in one
      eye, who received compensated medication. The hemodynamic parameters (PSV, EDV,
      IR) were measured by using color Doppler ultrasound and progression was evaluated
      by a repeated automated perimetry. The obtained values were statistically
      analyzed and compared with those obtained for the stable eye.

PMID- 29450357
TI  - Difference of refraction values between standard autorefractometry and Plusoptix.
AB  - Aim: Comparison between the objective refraction measurement results determined
      with Topcon KR-8900 standard autorefractometer and Plusoptix A09 photo
      refractometer in children. Material and methods: A prospective transversal study
      was performed in the Department of Ophthalmology of "Sf. Spiridon" Hospital in
      Iasi on 90 eyes of 45 pediatric patients, with a mean age of 8,82 +/- 3,52 years,
      examined with noncycloplegic measurements provided by Plusoptix A09 and
      cycloplegic and noncycloplegic measurements provided by Topcon KR-8900 standard
      autorefractometer. The clinical parameters compared were the following: spherical
      equivalent (SE), spherical and cylindrical values, and cylinder axis. Astigmatism
      was recorded and evaluated with the cylindrical value on minus after
      transposition. The statistical calculation was performed with paired t-tests and
      Pearson's correlation analysis. All the data were analyzed with SPSS statistical
      package 19 (SPSS for Windows, Chicago, IL). Results: Plusoptix A09 noncycloplegic
      values were relatively equal between the eyes, with slightly lower values
      compared to noncycloplegic auto refractometry. Mean (+/- SD) measurements
      provided by Plusoptix AO9 were the following: spherical power 1.11 +/- 1.52,
      cylindrical power 0.80 +/- 0.80, and spherical equivalent 0.71 +/- 1.39. The
      noncycloplegic auto refractometer mean (+/- SD) measurements were spherical power
      1.12 +/- 1.63, cylindrical power 0.79 +/- 0,77 and spherical equivalent 0.71 +/-
      1.58. The cycloplegic auto refractometer mean (+/- SD) measurements were
      spherical power 2.08 +/- 1.95, cylindrical power 0,82 +/- 0.85 and spherical
      equivalent 1.68 +/- 1.87. 32% of the eyes were hyperopic, 2.67% were myopic,
      65.33% had astigmatism, and 30% eyes had amblyopia. Conclusions: Noncycloplegic
      objective refraction values were similar with those determined by
      autorefractometry. Plusoptix had an important role in the ophthalmological
      screening, but did not detect higher refractive errors, justifying the
      cycloplegic autorefractometry.

PMID- 29450358
TI  - Recurrent inverted papilloma of paranasal sinus presenting as acute proptosis.
AB  - Objective. To describe the course of events that followed from the time of the
      diagnosis to the management of a rare case of recurrent inverted papilloma
      presenting as an acute proptosis. Methods. A seventy-year-old diabetic female
      patient presented with a painful left eye proptosis for 15 days. She had a
      history of resection of inverted papilloma of paranasal sinus followed by
      radiotherapy for eight years before. The examination revealed a 23 mm proptosis,
      with restricted ocular movements, corneal oedema, funnel shaped anterior chamber,
      and total retinal detachment with a complete visual loss. The lobulated fixed
      hard mass was palpable circumferentially but more in the inferior orbital
      compartment. The transconjunctival incisional biopsy showed features of highly
      undifferentiated cytology. The lid sparing exenteration was done under general
      anesthesia with cosmetic reconstruction. Results. Immunohistochemistry of
      exenterated mass was doubtfully suggestive of a small cell tumor. However,
      histopathology confirmed features of rhabdomyosarcoma. Conclusion. The present
      case study revealed rhabdomyosarcoma cytology presenting as an association
      inverted papilloma. Abbreviations : IP = Inverted papilloma, PNS = Paranasal
      sinus, SCC = Squamous cell carcinoma, IOP = Intraocular pressure, CT = Computed
      tomography.

PMID- 29450359
TI  - Complicated corneal ulcer. Case report.
AB  - Corneal ulcers are considered an ophthalmologic emergency because of their
      potential to permanently impair vision or perforate the eye. The therapeutic
      management includes medical therapy and in case of failure, surgical care such as
      amniotic membrane transplantation. We present the case of a 76-year-old male,
      admitted for sudden visual loss in the left eye, associated with ocular pain,
      tearing, and photophobia. The patient was diagnosed with superficial ulcerative
      keratitis with hypopyon and acute exogenous anterior uveitis for which he
      underwent medical treatment, both general and topic, with a good evolution during
      a month. After a month, the patient presented with the corneal ulcer perforated.
      Surgery was performed in the left eye by covering the ocular surface with an
      amniotic membrane using the Motowa's sandwich technique. After one year, the same
      patient was successfully operated for cataract removal and posterior chamber
      intraocular lens implantation in the left eye.

PMID- 29450360
TI  - Choroidal melanoma suspect. Conservative treatment and evolution. Case report.
AB  - We present the case of a 42-year-old female who presented to our clinic for
      phosphenes in the left eye, occurring along with eye movement. A diagnosis of
      choroidal melanoma suspect was made. Due to the patient's profile, young, active
      woman, surgeon, and the limited therapeutic options in Romania, a conservative
      treatment and brachytherapy were chosen, which were successfully performed
      abroad. The patient has been followed-up, so far, for five years after the
      procedure, with spectacular results.

PMID- 29450361
TI  - Pseudo-Foster Kennedy Syndrome - a case report.
AB  - Objective: To report a case of Pseudo-Foster Kennedy (PFK) syndrome and describe
      its clinical and paraclinical particularities, as well as the diagnostic
      difficulties and established treatment. Methods: The case of a 60-year-old male
      patient with sudden, painless visual impairment in the left eye (LE), and a
      medical history of old optic nerve atrophy in his right eye (RE) was described.
      Results: The diagnosis of nonarteritic anterior ischemic optic neuropathy (NAION)
      was established based on the medical history, local and general clinical and
      paraclinical examination, and temporal artery biopsy. Conclusions: Although there
      is no current generally accepted treatment for NAION, a correct diagnosis and
      supportive treatment may contribute to the improvement in visual acuity (VA),
      improvement that in this case remained stable for 6 months after the onset. The
      patient is still being monitored and no relapses have been noted.

PMID- 29450362
TI  - Can subtenon methylprednisolone acetate be a choice for the acute non-arteritic
      ischemic optic neuropathy treatment?
AB  - Nonarteritic ischemic optic neuropathy is characterized by sudden, painless,
      unilateral vision loss. A case of an acute NAION patient who was treated with
      subtenon methyl prednisolone acetate was presented. The patient, a 65-year-old
      male, presented vision loss for two days. The total ophthalmologic examination,
      fundus photography, and automated perimetry were applied to the patient before
      and after 1, 3, and 6 months from injection. The visual acuity increased from 0,1
      to 0,3 in the first month and to 0,7 at the last visit, the visual field defect
      being mostly improved. This case showed that 40 mg of subtenon methyl
      prednisolone acetate injection was an effective and safe treatment method for
      acute NAION. However, a large randomized controlled trial is needed to assess the
      efficacy of subtenon methyl prednisolone acetate as a treatment for NAION.

PMID- 29450364
TI  - Matrix regenerative therapy.
AB  - The extracellular matrix (ECM) is responsible for many of the cell behavior
      processes, including cell proliferation and growth, survival, change in cell
      shape, migration, and differentiation. The most important component of the ECM is
      heparan sulfate (HS), because it insures the storage of many cell communication
      proteins, necessary for the continuous and identical renewal of cells and thus
      for tissue regeneration. Regenerating agents (RGTA(r)) are bioengineered
      structural analogues of heparan sulfate glycosaminoglycans that replace the
      degraded endogenous HS of the ECM. In the ophthalmological field, RGTA(r)
      represents an innovative approach for the improvement of the ocular surface wound
      healing and matrix remodeling and plays a role in controlling and regulating the
      wound healing process in various ocular diseases.

PMID- 29450365
TI  - Uveitis-Glaucoma-Hyphaema Syndrome. General review.
AB  - Uveitis-Glaucoma-Hyphaema Syndrome (UGH syndrome, or "Ellingson" Syndrome) is a
      rare condition caused by the mechanical trauma of an intraocular lens
      malpositioned over adjacent structures (iris, ciliary body, iridocorneal angle),
      leading to a spectrum of iris transillumination defects, microhyphaemas and
      pigmentary dispersion, concomitant with elevated intraocular pressure (IOP). UGH
      Syndrome can also be characterized by chronic inflammation, secondary iris
      neovascularization, cystoid macular edema (CME). The fundamental step in the
      pathogenesis of UGH syndrome appears to arise from repetitive mechanical iris
      trauma by a malpositioned or subluxed IOL. These patients have uncomplicated
      cataract implants and return for episodes of blurry vision weeks to months after
      surgery. This may be accompanied by pain, photophobia, erythropsia, anterior
      uveitis, hyphaema along with raised intraocular pressure. A careful history and
      examination, as well as appropriate investigations can confirm the diagnostic.
      Treatment options are IOL Explantation exchange, topical and systemic medication,
      and cyclophotocoagulation, the placement of a Capsular Tension Ring to
      redistribute zonular tension and Anti-vascular endothelial growth factor (anti
      VEGF) Therapy.

PMID- 29450366
TI  - Is Laser Assisted Capsulotomy better than standard CCC?
AB  - Objectives: To compare the safety and intraoperative difficulties of two
      capsulorhexis techniques for white intumescent cataract: Femtolaser-assisted
      capsulorhexis and manual capsulorhexis performed in 2-3 stages, with the Utrata
      forceps. Materials and methods: A prospective comparative study that included 28
      eyes divided into 2 equal groups in which capsulorhexis was performed by using
      the 2 methods. In the first group, the capsulorhexis was executed by using LenSx
      Femtolaser. In the second group, an Utrata forceps was used to perform a manual 2
      3 steps capsulorhexis as follows: a small 2-3 mm capsulorhexis was performed
      after the staining of the anterior capsule with Trypan Blue along with a good
      pressurization with viscoelastic substance. The liquefied cortex was aspirated,
      followed by the enlargement of the capsulorhexis. In some cases, the enlargement
      was made after IOL implantation. Results: In the Femtolaser group, the capsule
      was completely detached in 13 cases and only in one case, the capsule had a few
      bridges which detached easily, without endangering the capsulorhexis integrity.
      Its size was 4,9 mm in all cases. In the group in which capsulorhexis was
      performed with the Utrata forceps in 2-3 stages, this was complete, circular and
      relatively well centered in all cases, but the size varied between 4,5 and 5,5
      mm. Conclusions: Femtosecond laser-assisted capsulorhexis was round, well
      centered and of a desired size of 4,9 mm. The manual capsulorhexis with the
      Utrata forceps depends on the surgeon's skill and experience and requires a good
      local anesthesia, the coloring of the anterior capsule with Tripan Blue, using a
      large quantity of cohesive viscoelastic substances and sometimes using micro
      incision forceps for helpful maneuvers. The size and centering of the
      capsulorhexis are not always identical with the intended ones.

PMID- 29450367
TI  - One year refractive outcomes of Femtosecond-LASIK in mild, moderate and high
      myopia.
AB  - Purpose: To evaluate the safety, efficacy, predictability and stability for a
      cohort of myopic eyes treated by Femtosecond-LASIK procedure. Methods: 60 eyes
      (36 patients) with different degrees of myopia that underwent refractive surgery
      by using the Femtosecond-LASIK technique were prospectively evaluated for 12
      months. The mean preoperative spherical equivalent value was -3.827 +/- 1.410
      diopters (D) (range: -8.125 to -1.375 D). VisuMax(r) femtosecond laser was used
      for cutting the corneal flap and then the Mel80(r) excimer laser for the stromal
      ablation. Results: Mean age was 30.80 +/- 5.745 years (range: 21 to 46 years)
      with 75% female patients. Postoperative spherical equivalent at 12 months was
      within +/-0.25 D of emmetropia in 90% of the eyes and within +/-0.50 D of
      emmetropia in 100% of the eyes. All the eyes achieved an uncorrected distance
      visual acuity (UDVA) of 1.0 (decimal scale). No eye lost lines of preoperative
      corrected distance visual acuity (CDVA). No major intraoperative or postoperative
      complications were encountered. Conclusions: Femtosecond-LASIK seems to be a
      suitable option for the correction of mild, moderate, and high myopia, as the
      procedure showed to be safe, effective, and predictable for the treatment of
      myopic refractive errors.

PMID- 29450368
TI  - Topical administration of Metamizole and its implications on vascular reactivity
      in Wistar rats- Experimental research.
AB  - Aim: The aim of this paper was to describe the possible implications of topical
      (ocular) administration of Metamizole on vascular reactivity of the iris in
      Wistar rats. No other study regarding its topical use was found. Methods: Male
      adult Wistar rats were anaesthetized with Ketamine 100 mg /kg body weight -
      injected intraperitoneally - while maintaining spontaneous respiration and the
      blink reflex. After selecting the area of interest (long posterior ciliary artery
      - LPCA), manual adjustments of the image magnitude, clarity, and brightness were
      made, and the experiment began. The image recording lasted 10 minutes. Results:
      Metamizole induced a slight vasoconstriction that started with the initial moment
      for all the doses used. After the topical administration of Metamizole, we did
      not observe an increase of the vascular diameter of LPCA in a dose dependent
      manner. The saline solution used as a negative control did not modify the vessel
      diameter. Conclusions: Metamizole (dipyrone) is a non-opioid drug, which is
      commonly used in human and veterinary medicine. It is the most popular first-line
      analgesic in various populations. In some cases, this agent is still incorrectly
      classified as a non-steroidal anti-inflammatory drug. The high analgesic efficacy
      of metamizole, as well as its spasmolytic effect, makes it a very important
      pharmaceutical agent that could be used in the therapy of various eye disorders
      in humans and in animals. Abbreviations: COX = Cyclooxygenase; LPCA = Long
      Posterior Ciliary Artery; PRP = panretinal photocoagulation; PDR = proliferative
      diabetic retinopathy; Sec = second(s); VSPR = very severe non proliferative
      diabetic retinopathy.

PMID- 29450369
TI  - Schirmer test changes after 20 gauge and 23 gauge pars plana vitrectomy.
AB  - Objective: To evaluate the short-term changes in Schirmer I test (ST) after pars
      plana vitrectomy and to compare the results between 23 gauge and 20 gauge
      vitrectomy surgeries. Methods: 42 patients who underwent pars plana vitrectomy
      for posterior segment diseases were included in this prospective, non-randomized,
      comparative study. The choice of sclerotomy gauge was at the surgeons'
      discretion. ST values were recorded before and at 1 and 3 months after
      vitrectomy. Results: 20 patients in 23 gauge and 22 patients in 20-gauge group
      with a mean age of 59.9 +/- 13.5 years were included. The mean preoperative ST
      values decreased significantly in both groups at 1 and 3 months after surgery
      (all P < 0.01). The ST values in the fellow eyes were the same, at baseline and
      during the follow up (P > 0.05). At 3 months visit, 15 eyes (35.7%) had abnormal
      ST measurements. There was no statistically significant difference in the changes
      in the ST measurements between the two groups at one month (P = 0.7), however, 3
      months after surgery, the mean decrease in the ST measurements was significantly
      higher in the 20 gauge group (P = 0.03). At 3 months, 4 eyes in the 23 gauge
      group (20%) and 11 eyes in the 20 gauge group (50%) had abnormal ST measurements
      (P = 0.05). Conclusions: Although both 20 and 23-gauge vitrectomy decrease the ST
      measurements postoperatively, the value is less affected by the 23-gauge
      vitrectomy.

PMID- 29450370
TI  - Terson's Syndrome - case report.
AB  - Terson's Syndrome is represented by a vitreous, retrohyaloid, retinal, or
      subretinal hemorrhage occurring consequent to an acute intracranial hemorrhage or
      elevated intracranial pressure. The outcome may include a complete clearing of
      the blood and the restoration of VA or persistent hemorrhage. This report
      presents the case of a 43-year-old woman who underwent bilateral surgery for a
      persistent vitreous hemorrhage and a hematoma underneath the internal limiting
      membrane in the left eye. The event followed shortly after a subarachnoid
      hemorrhage due to the rupture of a posterior communicating artery aneurism.
      Vitrectomy was performed in both eyes, together with the peeling of the internal
      limiting membrane in the left eye, followed by a bilateral good outcome.

PMID- 29450371
TI  - Necrotizing retinitis of multifactorial etiology.
AB  - Introduction. We present the case of a 73-year-old woman with osteoporosis, who
      presented to the emergency room with a sudden vision loss and ocular pain in the
      right eye, which appeared two days before. The patient mentioned loss of
      appetite, weight loss for three months and low fever for two weeks. Materials and
      methods. Among the ophthalmological findings, the most important were panuveitis,
      and large confluent necrotic areas in the peripheral retina. The patient was
      diagnosed with RE Panuveitis and acute necrotizing retinitis. Results. Blood
      exams showed leukocytosis and monocytosis, thrombocytosis and anemia. Further
      investigations showed high levels of Cytomegalovirus (CMV) anti IgG and Herpes
      Simplex (HS) type 1 virus anti IgM, urinary infection, and secondary hepatic
      cytolysis. The CT and MRI of the thorax and abdomen showed no sign of neoplastic
      disease, and no explanation for the CMV infection was found. The patient received
      general corticotherapy and antiviral therapy, and, after one month, RE BCVA was
      20/ 30. Particularity of the case. Acute necrotizing retinitis in an old patient
      with CMV and HSV type 1, associated with secondary hepatic cytolysis, without any
      other immunosuppressive disease and very good outcome.

PMID- 29450372
TI  - Penetrating corneal wound with traumatic cataract and intraocular foreign body
      case report.
AB  - Open globe injuries complicated with the presence of an intraocular foreign body
      mostly affect young males and represent a vision threatening condition. We
      presented the case of a 48-year-old male who presented to our emergency service
      due to ocular pain and blurred vision in his right eye. A metallic foreign body
      situated between 1 and 12 o'clock, near the corneoscleral limbus, that perforated
      the cornea, the iris, the anterior capsule of the lens and the lens, was detected
      at the slit-lamp examination. We decided to immediately remove the foreign body
      that was approximately 20 mm long. The following day, traumatic cataract had
      already developed, so we performed cataract extraction. Despite the dimensions of
      the intraocular foreign body, the retina was attached and there were no sign of
      retinal tears or vitreous haemorrhage. The proper management in this case led to
      good results in spite of the dimensions of the intraocular foreign body.
      Abbreviations: IOFB = Intraocular Foreign Body, IOL = Intraocular Lens, PVR =
      Proliferative Vitreo-Retinopathy.

PMID- 29450373
TI  - Diagnosis difficulties in a patient with progressive loss of vision - a case
      report.
AB  - The paper presents the case of a 57-year-old male patient who complained of slow
      progressive loss of visual acuity. Anamnesis revealed he was a heavy drinker and
      he was previously diagnosed with a pancreatic cancer, observed on the MRI. The
      clinical examination revealed ocular features that made the diagnosis difficult.
      Initially, it seemed to be a case of narrow angle glaucoma but further ocular
      examinations revealed macular thinning.

PMID- 29450374
TI  - Intraocular ossification. Case report.
AB  - Objective: To report a case of intraocular ossification, describe its
      particularities and review some of the pathogenesis theories. Methods: We
      described the case of a 31-year-old woman with a history of perforating trauma
      ten years before, who presented in our clinic for right eye pain. The patient
      wanted a cosmetic improvement so an evisceration was proposed. An intraocular
      hard yellowish mass, which had a histopathological examination, was found
      intraoperatively. Results: We diagnosed the case as an intraocular ossification,
      based on the medical history and histopathological specimen examination, which
      proved to be an ossified structure. Conclusions: In spite of a rare occurrence,
      our case emphasized the theory that trauma and subsequent neurogenic inflammation
      could lead to osseous metaplasia.

PMID- 29450375
TI  - Scheimpflug topographical changes after Femtosecond LASIK for mixed astigmatism -
      theoretical aspects and case study.
AB  - Objective: To evaluate the corneal topographical changes after Femtosecond-LASIK
      surgery in eyes with mixed astigmatism. Methods: We present the analysis of the
      corneal Scheimpflug topographies of a patient treated with Femtosecond-LASIK
      technique for bilateral mixed astigmatism. Results: Three-dimensional
      reconstruction maps and differential anterior curvature maps were used to
      demonstrate the ablation profile and its stability in time. Conclusions: Visual
      and refractive results were very good after surgery, being topographically
      confirmed by the corneal reshaping which was performed as planned, the achieved
      ablation being stable during the one-year follow-up period.

PMID- 29450377
TI  - Opinions regarding refractive surgery today in Romania.

PMID- 29450376
TI  - Subconjunctival ocular filariasis -Case report.
AB  - We are presenting the case of a patient who was clinically diagnosed with
      subconjunctival ocular dirofilariasis, confirmed by the parasitological
      examination. The treatment consisted in the surgical extraction of the parasite,
      a local treatment with antibiotics and steroidal anti-inflammatory mydriatic and
      general treatment with antihelminthic, antibiotic, analgesic, and anti
      inflammatory drugs. The intraoperative and postoperative evolution of the case
      was favorable.

PMID- 29450378
TI  - Ocular posterior pole pathological modifications related to complicated
      pregnancy. A review.
AB  - Ocular posterior pole modification are a pathological manifestation in
      complicated pregnancies, especially when pregnancy induced hypertension is
      present (PIH), as well as in preeclampsia (PE) or eclampsia. Nonetheless, as the
      pregnancy evolves, the possibility for an aggravated evolution with HELLP
      syndrome, disseminated intravascular coagulation, and idiopathic thrombocytopenic
      purpura may have an ocular manifestation that, mainly, implies a loss of visual
      field or acuity, that, left unattended, may constitute a permanent impairment.
      Pregestational conditions like pituitary adenoma or genetic pedigree for
      complement factor H gene (1q31.1) single nucleotide mutations could lead to
      central serous chorioretinopathy or retinal detachment with severe, ischemic,
      central cilioretinal artery or vein occlusion and optic nerve atrophy.
      Furthermore, although subtle in many cases, any new visual symptoms during
      pregnancy should constitute an alarming factor for obstetrical reevaluation and
      ophthalmological approach in order to preserve the mother's quality of life.

PMID- 29450379
TI  - Pseudophakic bullous keratopathy.
AB  - Pseudophakic bullous keratopathy is characterized by corneal stromal edema with
      epithelial and subepithelial bullae due to cell loss and endothelial
      decompensation through trauma during cataract surgery. Patients present decreased
      vision, tearing, and pain caused by ruptured epithelial bullae. Cataract affects
      approximately 20 million people worldwide, and this complication can occur in 1
      to 2% of the cataract surgeries. This study reviewed the bullous keratopathy
      etiopathogenesis and the clinical and surgical treatment available for this
      corneal disease.

PMID- 29450380
TI  - CAN Optical Coherence Tomography redefine amblyopia?
AB  - Introduction: For many years, amblyopia was regarded as a disorder of the visual
      system in which an organic cause could not be identified. Optical Coherence
      Tomography opens new horizons in understanding the etiopathology of amblyopia and
      seems to highlight morphologic anomalies in the retina of the amblyopic eye.
      Purpose: The objective of this paper is to analyze the macular thickness, optic
      nerve changes, and choroidal thickness found in patients diagnosed with amblyopia
      based on trials reported in the literature. Material and methods: This study
      analyzes 30 clinical trials regarding amblyopia evaluation with Optical Coherence
      Tomography. The research articles analyzed were published between 2006 - 2016 and
      were identified on PubMed database. Results: 19 research studies focused on
      macular and nerve optic changes, 7 on choroidal changes and 6 on retinal changes
      after occlusion. The results were discussed according to the type of amblyopia,
      alteration of macular thickness, optic nerve changes, ganglion cell layer
      changes, and alteration of choroidal thickness. Conclusions: The results are of
      great variability, and it seems that macula and choroid involvement is more
      frequently suggested compared with optic nerve involvement. Abbreviations: OCT =
      Optical Coherence Tomography, RNFL = Retinal Nerve Fiber Layer, GCC = Ganglion
      Cell Complex, ACD = Anterior Chamber Depth, BCVA = Best Corrected Visual Acuity.

PMID- 29450381
TI  - Insights in the treatment of congenital nasolacrimal duct obstruction.
AB  - Introduction: Congenital nasolacrimal duct obstruction is one of the most common
      causes of epiphora in newborns and the main cause of this condition is the
      persistence of Hasner membrane. Several treatment options are available, like
      conservative treatment, probing, irrigation, or more complex techniques.
      Objective: The objective of this paper is to discuss the efficiency of different
      treatment options addressing congenital nasolacrimal duct obstruction based on
      trials reported in literature. Methods: Clinical trials were identified on
      PubMed. The results were discussed regarding patient age, type of treatment and
      efficiency of the treatment. Results: 41 trials were reviewed. The rate of
      resolution according to different treatment options was the following:
      conservative treatment 14.2-96%, probing 78-100%, irrigation 33-100%, silicon
      tube intubation 62-100%, inferior turbinate fracture 54.7-97%, balloon
      dacryocystoplasty 77%, endoscopic intranasal surgery 92.72%, and
      dacryocystorhinostomy 88.2-93.33%. Conclusions: The first choice in uncomplicated
      cases should be a conservative treatment, which can be followed until the age of
      1 year, while in complicated cases other solutions should be considered.
      Abbreviations: CNDO = Congenital nasolacrimal duct obstruction, DCR =
      Dacryocystorhinostomy, MCI = Monocanalicular intubation, BCI = Bicanalicular
      intubation.

PMID- 29450382
TI  - IRIDEX MicroPulse P3: innovative cyclophotocoagulation.
AB  - Purpose: To present the new IRIDEX MicroPulse P3 (MP3) technology in patients
      with refractory glaucoma and our preliminary results at 1 week and 1 month
      postoperatively. Methods: IRIDEX MP3 laser cyclophotocoagulation was performed in
      7 eyes of 7 patients under retrobulbar anaesthesia with lidocaine 2% in the
      operating room. Each eye received two treatments of 80-90s over the superior and
      inferior hemisphere, avoiding the temporal- and nasal-most clock hours. 810nm
      IRIDEX MP3 was set to 31,3% duty cycle (0,5ms treatment pulse followed by 1,1 ms
      of rest). Postoperative topical steroids were prescribed for 1 week. Results:
      Mean IOP decrease at 1 week was 60,3% and 33,4% at 1 month, with a mean topical
      hypotensive treatment reduction of 0,71 therapeutic agents. The procedure was
      safe in all cases and effective in 71% of the patients. Neovascular glaucoma
      patients registered high IOP levels 1 month postoperatively in spite of medical
      and MP3 laser treatment. BCVA remained unchanged after undertaking the laser
      procedure. No significant inflammation, discomfort, or pain was reported. There
      were no complications such as hypotony, phthisis bulbi, and macular edema.
      Conclusions: IRIDEX MP3 represents an innovation in cyclophotocoagulation. It is
      non-destructive, repeatable, non-invasive, with a high safety profile. A mean IOP
      decrease of 33,4% was registered at 1 month. Patient comfort and recovery are
      favorable. Long-term results will prove its efficacy in the future.

PMID- 29450383
TI  - Eyesight quality and Computer Vision Syndrome.
AB  - The aim of the study was to analyze the effects that gadgets have on eyesight
      quality. A prospective observational study was conducted from January to July
      2016, on 60 people who were divided into two groups: Group 1 - 30 middle school
      pupils with a mean age of 11.9 +/- 1.86 and Group 2 - 30 patients evaluated in
      the Ophthalmology Clinic, "Sf. Spiridon" Hospital, Iasi, with a mean age of 21.36
      +/- 7.16 years. The clinical parameters observed were the following: visual
      acuity (VA), objective refraction, binocular vision (BV), fusional amplitude
      (FA), Schirmer's test. A questionnaire was also distributed, which contained 8
      questions that highlighted the gadget's impact on the eyesight. The use of
      different gadgets, such as computer, laptops, mobile phones or other displays
      become part of our everyday life and people experience a variety of ocular
      symptoms or vision problems related to these. Computer Vision Syndrome (CVS)
      represents a group of visual and extraocular symptoms associated with sustained
      use of visual display terminals. Headache, blurred vision, and ocular congestion
      are the most frequent manifestations determined by the long time use of gadgets.
      Mobile phones and laptops are the most frequently used gadgets. People who use
      gadgets for a long time have a sustained effort for accommodation. A small amount
      of refractive errors (especially myopic shift) was objectively recorded by
      various studies on near work. Dry eye syndrome could also be identified, and an
      improvement of visual comfort could be observed after the instillation of
      artificial tears drops. Computer Vision Syndrome is still under-diagnosed, and
      people should be made aware of the bad effects the prolonged use of gadgets has
      on eyesight.

PMID- 29450384
TI  - Plateau Iris - Therapeutic options and functional results after treatment.
AB  - We present the therapeutic options and functional results in patients with
      plateau iris (syndrome or configuration) in consecutive case series. Material and
      method: Our study included newly diagnosed patients with acute angle closure by
      "plateau iris" (configuration or syndrome), between June 2016 and April 2017.
      Series of 8 consecutive patients met the inclusion criteria, all being females.
      All the patients underwent an individualized treatment according to the
      underlying mechanism and evolution. Functional results (visual acuity, IOP,
      topical medication) were reported in the current paper. Results: For 10 months,
      we diagnosed 14 eyes, from 9 patients with acute angle closure by Plateau Iris,
      distributed as it follows: 6 eyes with closed angle glaucoma (optic disk and
      visual field changes), 8 eyes with plateau iris syndrome and 2 eyes with plateau
      iris configuration. 7/ 8 patients were misdiagnosed with primary open angle
      glaucoma, whereas only one patient had the correct diagnosis of closed angle
      glaucoma and underwent peripheral laser iridotomy. As treatment options in our
      study, we recommended and performed argon laser peripheral iridoplasty +
      iridotomy in 10/ 14 eyes, cataract lens was extracted in 4 eyes and then replaced
      with PC-IOL, whereas 2 eyes required a filtering anti-glaucoma surgery
      (trabeculectomy + PI). 2 eyes from the same patient could not be treated as
      intended as the patient refused the treatment. In this unique case, Pilocarpine
      (4%) was temporarily indicated. Conclusion: Plateau iris represents a diagnostic
      trap, but based on a thorough gonioscopic examination and a good patient history,
      the right diagnosis can be made, all along with a correct therapeutic approach.

PMID- 29450385
TI  - The effect of intravitreal bevacizumab in a rare case of retinal dystrophy with
      secondary cystoid macular edema.
AB  - The authors presented a clinical case of retinitis punctate albescens in a 26
      year-old female patient, with a family history of typical retinitis pigmentosa
      (father) and bilateral cystoid macular edema treated with anti-VEGF
      (bevacizumab).

PMID- 29450386
TI  - Penetrating keratoplasty: from aid dependence to independence.
AB  - The authors present five cases of bilateral corneal disorders, on which they
      performed penetrating keratoplasty. All five patients were clinically blind and
      after the surgery on one eye, they gained their visual independence. Visual
      acuity, intraocular pressure, fundus examination, and ultrasonography were used
      to evaluate the patients before and after the surgery.

PMID- 29450387
TI  - Orbital cellulitis and brain abscess - rare complications of maxillo-spheno
      ethmoidal rhinosinusitis.
AB  - Sinus infections can be complicated by ocular infections and, in late phases, by
      brain parenchyma infection. The article debates the case of a 12-year-old patient
      suffering from paucisymptomatic maxillo-spheno-ethmoidal rhinosinusitis, which
      was later complicated by orbital cellulitis, ending with the development of a
      brain abscess. The treatment is complex, initially targeting the source of the
      infection through draining the collection by middle maxillary antrostomy and
      anterior posterior ethmoidectomy, then the ablation of the brain abscess and
      postoperatively with prolonged massive antibiotherapy. Abbreviation: URI = upper
      respiratory infection, CT = computer tomography, MRI = magnetic resonance
      imaging, BA = brain abscess, VAS = visual scale of pain, ENT = ear, nose, throat,
      RE VA = right eye visual acuity, RE = right eye, CSF = cerebrospinal fluid.

PMID- 29450388
TI  - Rare case of ocular tuberculosis in a diabetic patient: diagnostic and
      therapeutic dilemmas.
AB  - We present the case of a patient who was diagnosed by chance with macular
      hypopyon during a conventional interdisciplinary examination. The clinical
      context and the association of a systemic disease, such as uncontrolled type 1
      diabetes, rendered further investigations in this patient. Due to his
      immunocompromised status, etiology such as ocular fungi, lymphomas, tuberculosis
      was taken into account. Thorough complex investigations oriented the diagnosis
      towards ocular tuberculosis involvement.

PMID- 29450390
TI  - Editorial.

PMID- 29450389
TI  - Unilateral Eales' disease a case report.
AB  - Introduction. Eales disease is an idiopathic peripheral vascular occlusive
      disease characterized by inflammation, ischemia, and retinal neovascularization
      and is hallmarked by recurrent vitreous hemorrhages and vision loss. Case report.
      We present a case of a 48-year-old female with recurrent floaters and decreased
      vision in her right eye. The onset of symptoms was in 2007 when a diagnose of
      retinal vasculitis was made. She had no accompanying systemic signs and symptoms
      and no history of ocular trauma or previous tuberculosis infection. The eye
      condition was managed only with intermittent focal laser treatment, because the
      general treatment with steroids was not efficient and poorly tolerated. After the
      laser treatment, the visual acuity completely recovered and there was no
      recurrence of vitreous hemorrhage. The case particularity was the unilaterality
      after 9 years from the onset.

PMID- 29450391
TI  - Citicoline - a neuroprotector with proven effects on glaucomatous disease.
AB  - Citicoline is the generic name of cytidine-5'-diphosphocholine (CDP-choline), an
      endogenous compound that is able to increase the levels of neurotransmitters in
      the central nervous system by interacting with the synthesis of cellular
      membranes phospholipids, especially phosphatidylcholine. Exogenous Citicoline,
      administered by ingestion or injection, is hydrolyzed and dephosphorylated in
      order to form cytidine and choline, which resynthesize CDP-choline inside brain
      cells. It has proven neuroprotective effects in Alzheimer disease, stroke, and
      Parkinson's disease, as well as in glaucoma and amblyopia. Citicoline acts as a
      neuroprotector for those patients with progressive glaucomatous disease in spite
      of well-controlled intraocular pressure. The purpose of this review was to
      outline the main features of Citicoline and the evidences of its effect in
      glaucoma.

PMID- 29450392
TI  - Glaucoma after penetrating keratoplasty.
AB  - Penetrating keratoplasty is a surgical intervention that despite the progress of
      surgical techniques and of postoperative treatment continues to have numerous
      complications. Many of them, such as graft rejection, significant astigmatism,
      cystoid macular edema, or cataract lead to important limitations of the visual
      function. Glaucoma is possibly the most dangerous complication following PK,
      leading to loss of the visual potential of the eye due to irreversible damage to
      the optic nerve. Identifying the risk factors permits an attentive follow-up and
      rapid treatment of the postoperative IOP rises. Maybe the most important is that
      preexisting glaucoma should be rightly diagnosed and controlled before PK,
      medically or, if necessary, surgically. Abbreviations: PK = penetrating
      keratoplasty, IOP = intraocular pressure, PAS = peripheral anterior synechiae, TM
      = trabecular meshwork, DM = Descemet membrane, GAT = Goldmann applanation
      tonometry, MMC = mitomycin C, CAI = carbonic anhydrase inhibitors, 5-FU = 5
      fluorouracil.

PMID- 29450393
TI  - Management of diplopia.
AB  - Diplopia (seeing double) is an ophthalmologic complaint found mainly in elder
      patients. It can have both ocular and neurological causes. A careful history and
      clinical examination must detail the type of diplopia (monocular/ binocular),
      onset, and progression, associated and relieving factors. In case of monocular
      diplopia, refraction and biomicroscopic examination of the ocular media are
      mandatory. The cause of ocular misalignment for binocular diplopia must be
      determined and life-threatening conditions (such as posterior communicating
      artery aneurysm) must imply an immediate treatment. Management and treatment is
      always according to the specific cause of diplopia.

PMID- 29450395
TI  - Investigating the perception of Romanian adults on ophthalmology services from an
      experiential marketing perspective.
AB  - Nowadays, we live in a world in which we are daily bombed by hundreds of
      advertisements. Specialists have to discover other channels or embed attractive
      elements in the advertisements' messages to cut through the clutter and catch the
      consumers' attention. The evolution of the concept of service has changed from
      the commercial status to determining a lifestyle. Buying a service has led to a
      change in the consumer behavior. Consumers want to buy services that dazzle their
      senses, touch their hearts, and stimulate their minds, not as before, excellent
      or satisfying. Ophthalmology is the medical specialty that is the most oriented
      toward outpatient care, as hospitalization is required only in a small percentage
      of cases. The objective of this case study was to investigate the perception of
      Romanian adult consumers on ophthalmology services from an experiential marketing
      perspective, by using the Focus Group method. Ophthalmology requires a wide range
      of skills due to the diversity of consumers who demand specialized consultations.
      Experiential marketing is a valuable strategy that ophthalmologic organizations
      may use to target specific consumers. The purpose of this case study was to
      identify the perceptions of Romanian adults on experiential marketing campaigns
      and determine the degree to which these campaigns influenced their decisions of
      buying an ophthalmologic service. Using a snowball sampling technique we have
      sent a filter questionnaire to 40 people on the internet. The filter
      questionnaire consisted of questions about wearing eyeglasses, the period of
      wearing them, the last ophthalmologic consultation, the type of ophthalmologic
      clinic they were going to, age and education. The respondents revealed there is
      almost no visibility on promoting services even if there is an upsurge of
      organizations offering this type of health service in the Romanian ophthalmology
      sector.

PMID- 29450396
TI  - Transnasal endoscopic assisted dacryocystorhinostomy.
AB  - Transnasal endoscopic dacryocystorhinostomy is a good alternative for external
      DCR. It is considered a safe and efficient technique with successful results,
      comparable or even better than the external technique. Advanced knowledge of the
      endoscopic anatomy and the lacrimal system is necessary to perform the procedure
      safely, and to obtain good surgical outcomes. The aim of the paper is to analyze
      the changes of the endoscopic technique and to improve it. The transnasal
      endoscopic dacryocystorhinostomy surgical technique is described in a "step by
      step" manner. Also the surgical technologies that can be used for this
      intervention are presented, focusing on the cold instruments.

PMID- 29450394
TI  - Update on retinal vascular caliber.
AB  - Retinal vessels are the only blood vessels that can be viewed directly, in vivo,
      repetitively and non-invasively. Retinal vessel caliber is influenced by
      physiological (age, sex, race, blood pressure, blood glucose, body mass index)
      and pathological (atherosclerosis, dyslipidemia, smoking) determinants. There are
      studies on large population groups that demonstrate the associations between
      retinal vasculature and subclinical or clinical changes in systemic diseases
      (hypertension, diabetes, stroke, renal or cardiac diseases). The assessment of
      retinal vessels can provide information about the pathophysiology of many
      diseases, but it also has a direct applicability in clinic, being used as a
      screening method that predicts the risk of their occurrence.

PMID- 29450397
TI  - Transnasal endoscopic orbital decompression.
AB  - Transnasal endoscopic orbital decompression is a viable alternative for external
      orbital decompression. Today, it can be performed due to the great development of
      endoscopic technology and specific endoscopic surgical instruments. It requires
      strong anatomic knowledge and skilled hands. We present our experience with
      endoscopic orbital decompression focusing on the surgical technique used in our
      department. The surgical maneuvers must be firm and gentle protecting the local
      risk elements and respecting the orbital content.

PMID- 29450398
TI  - Cataract surgery outcome in patients with non-glaucomatous pseudoexfoliation.
AB  - Aim. To study the outcome of cataract surgery in eyes with pseudoexfoliation
      without signs of glaucoma. Methods. This prospective study was done over nine
      months on patients with pseudoexfoliation undergoing small incision cataract
      surgery. Only patients with normal intraocular pressure (Central Corneal
      Thickness Corrected), normal cup disc ratio and open angles were included.
      Patients on anti-glaucoma medication were excluded. Patients underwent surgery
      performed by a single senior surgeon. Intraoperative and postoperative day (POD)
      1 findings were noted. Results. The mean age of the patients was 61.60 years +/ -
      10.21 years. Males were 46% (n=16). Right eye was operated upon in 60% of the
      cases (n=21). The mean pupil dilation was 5.1 mm +/ - 1.47 mm. The postoperative
      day 1 visual acuity of the patients was logMar 1.02 +/- 0.64 and the mean POD 1
      intraocular pressure was noted to be 26.23 mmHg +/ - 11.40 mmHg. Five cases had a
      zonular dialysis intraoperatively due to weak zonules. 11 cases had high anterior
      chamber reaction of 2+ or more. Four cases had unavoidable sphincter tears and
      two cases had iridodialysis superiorly during nucleus delivery. Conclusions.
      Intraoperative complications should be anticipated in patients with
      pseudoexfoliation even without glaucomatous changes due to poor pupillary
      dilation and zonular weakness. First postoperative day visual acuity in
      pseudoexfoliation patients undergoing cataract surgery was found to be low due to
      severe anterior chamber inflammation causing elevated intraocular pressure and
      corneal edema. Abbreviations. POD = Postoperative day, PEX = Pseudoexfoliation
      syndrome, LOXL 1 = Lysyl oxidase-like 1, IOP = Intraocular pressure, AC =
      Anterior chamber, IOL = Intraocular lens.

PMID- 29450399
TI  - Functional results of cataract surgery in the treatment of phacomorphic glaucoma.
AB  - Purpose. Analysis of functional outcome and complications reported in patients
      diagnosed with phacomorphic glaucoma, in which phacoemulsification or
      extracapsular extraction of the lens was performed. Methods. The retrospective
      study included 38 eyes diagnosed with phacomorphic glaucoma. In 25 cases, group
      1, the lens was removed by phacoemulsification and in 13 cases, group 2, by
      extracapsular extraction. Intraocular pressure, visual acuity, and anterior
      chamber depth were evaluated preoperative and postoperative. The incidence of
      intra and postoperative complications was analyzed. The minimum follow-up period
      was 12 months. Results. The mean IOP decreased from the preoperative value of
      38.4 +/ - 11.3 mmHg to 13.5 +/ - 3.4 mmHg in group 1 and 11.5 +/ - 3.2 mmHg in
      group 2. Persistent corneal edema was observed in 32% patients from group 1 and
      23% of the patients from group 2. The inflammatory reaction of anterior chamber
      prevailed in patients from group 2 (46.1%). ACD modified from the preoperative
      mean of 1.3 +/- 0.5 mm to 2.3 +/- 0.2 mm in both groups. At the end of follow-up
      in both groups, the average BCVA was 0.6. 18.42% of the cases required long-term
      topical hypotensive therapy. Conclusions. Both phacoemulsification and
      extracapsular extraction were safe and effective procedures in the treatment of
      phacomorphic glaucoma, ensuring a rapid functional recovery and a satisfactory
      long-term IOP control. Although the rate of immediate postoperative complications
      and the final functional outcome were better in patients treated with
      phacoemulsification, not all the cases could be subjected to this type of
      surgery.

PMID- 29450400
TI  - Incidence of ocular hypertension after intravitreal injection of anti-VEGF agents
      in the treatment of neovascular AMD.
AB  - Purpose. The assessment of the incidence of ocular hypertension over a period of
      1 year in patients treated with multiple intravitreal injections of anti-VEGF
      agents for neovascular AMD. Methods. The study comprised 58 eyes diagnosed with
      neovascular age-related macular degeneration and receiving PRN intravitreal
      treatment with anti-VEGF agents (bevacizumab or aflibercept). The follow-up
      period was 1 year. Intraocular pressure was measured by using the Goldmann
      applanation tonometry before the intravitreal injection, at 24 hours after the
      administration of the anti-VEGF agent and at 1 and 4 weeks. Patients diagnosed
      with glaucoma or who underwent ophthalmic surgery were excluded. Results. The
      patients received an average of 7.54 intravitreal injections. The mean baseline
      intraocular pressure was 15.3 mm Hg; 19.8 mm Hg at 24 hours; 17,4 mmHg at 1 week
      and 14.8 mmHg at 4 weeks after the administration of the anti-VEGF agent. 4
      patients required long-term topical hypotensive treatment. Raised intraocular
      pressure was related to increased frequency of treatment. At 1 year follow up, an
      average difference of 2.1 mmHg compared to baseline was registered in the cases
      that have received more than 6 intravitreal injections. By comparison, in the
      cases treated with a reduced number of doses of intravitreal anti VEGF agent, the
      difference from baseline was 0,9 mmHg. There were no significant differences in
      mean IOP depending on the anti VEGF (bevacizumab or aflibercept) agent used.
      Conclusions. Intravitreal treatment with anti VEGF agents produces a transient
      increase in intraocular pressure, predominantly immediately following
      administration, without causing long-term increased values.

PMID- 29450401
TI  - Non-parametric tests in detecting glaucoma progression.
AB  - Automated perimetry still represents the gold standard in long term glaucoma
      monitoring. On a daily practice basis, glaucoma progression analysis could be
      difficult due to the long time needed to detect, confirm, and quantify the
      progression rate. Moreover, "trend" and "event" analysis require a good
      theoretical basis to perform and interpret. Aim of study was to present an
      alternative method to conventional Glaucoma Progression Analysis (Humphrey Visual
      Field Analyzer, Carl Zeiss(r) Inc.) applied for the early detection of glaucoma
      progression. Such an "event" analysis orients the clinician in a fast manner on
      the progression profile in glaucoma patients and might adapt the follow up visits
      accordingly. Method and material: 41 eyes from 41 patients with open angle
      glaucoma were studied in a longitudinal manner, over a 24 months' time interval
      from diagnosis. Results: in the GPA analysis, a positive "event" (progression)
      was detected in 11/ 41 eyes (26.82%). Non-parametric analysis confirmed
      progression in all GPA cases, and additionally found 8 more eyes with positive
      progression (46.34% studied eyes). Mc Nemar concordance analysis between tests
      was good and relevant (kappa index k=0.596, p=0.000), with positive correlation
      (r=0.652, p=0.008). In conclusion, NPA tends to overestimate the number of
      progression cases in a cohort, but it can easily orient the clinician on the
      profile of the followed patients. In the first years, the GPA analysis can be
      highly inaccurate, but there is a great need to detect which patients are at
      significant risk for vision loss (fast progressors). Yet, combining the two
      methods of detection of glaucoma progression, the practitioners might direct
      their selected interest and attention towards observing a larger than expected
      number of patients who are at risk for vision loss over time due to glaucoma, but
      not necessarily in a fast manner.

PMID- 29450402
TI  - Modeling the consumer's perception of experiential marketing in the Romanian
      private ophthalmologic services.
AB  - Introduction. The importance of experience in marketing grew, as the concept
      itself is very personal and difficult to measure. Experience turns out to be
      complicated but once placed in a context it gets significant features. As the
      health care competitive environment increases, marketers are looking for new and
      effective methods of engaging consumers by using experiential marketing
      strategies. Moreover, little is known about the consumers' perceptions related to
      ophthalmologic services. Aim. The objective of this paper was to measure the
      consumer's perception of experiential marketing in the Romanian private
      ophthalmologic services by using structural equation modeling. Materials and
      Methods. The Experiential Marketing model consisted of the following components:
      Sense Experience, Feel Experience, Think Experience, Act Experience and Relate
      Experience as well as the consequences of applying Experiential Marketing in the
      form of willingness to purchase a service, generating word-of-mouth communication
      and building consumer loyalty. The sampling method was non-probabilistic, using
      the snowball technique and the sample was made up of 190 people who wore
      eyeglasses for more than 3 years. The instrument for data collection was a self
      administered questionnaire, which consisted of 2 parts: the first section
      contained several demographic questions and the second section encompassed closed
      end questions related to the perception of private ophthalmologic services from
      an experiential marketing perspective. All the second section questions were
      measured on a 5-point Likert scale ranging from 1 with Strongly Disagree to 5 to
      Strongly Agree. The data analysis was conducted in SPSS and the structural
      equation modeling was performed in WarpPLS version 6.0. Findings. There were
      71.05% respondents, who appreciated the application of experiential marketing in
      private ophthalmologic services, followed by 18.95%, who were confused. The
      demographic profile of respondents encompassed the following features: females
      with the ages between 36 and 45, from the rural area and with a middle level of
      education, their private ophthalmologic consultation frequency was at every 3
      months and they also declared having a stable physician. Going further with the
      analysis, 89.63% of the respondents admitted they were willing to buy a private
      ophthalmologic service based on the experiential marketing application
      strategies. The design of a model containing both the constituent elements of the
      experimental marketing and its consequences in ophthalmologic services was
      conducted by modeling with structural equations in WarpPLS version 6.0 software.
      Thus, the validity of the model was assessed with the Cronbach's alpha
      coefficients, Composite reliability values, as well as with the Average Variance
      Extracted coefficients, and the fitness of the model was determined by using the
      ARS, APC, and AVIF values, respectively. According to the beta coefficients and
      levels of statistical significance (p<0.05), some hypotheses have been rejected
      or negative relationships have been established between dependent and independent
      variables. Conclusions. Sense experience had a negative impact on WOM and
      consumer loyalty, Think Experience had a negative influence on the WOM, Relate
      Experience had a negative impact on consumer Loyalty, as well as Relate
      Experience had a negative impact on willingness to purchase an ophthalmologic
      service. In contrast, the following positive relationships were established: Feel
      Experience established a positive relationship with WOM and consumer loyalty,
      Think Experience presented a positive impact both on consumer loyalty and on
      willingness to purchase an ophthalmologic service, Act Experience presented a
      positive impact on WOM and willingness to purchase and last, willingness to
      purchase an ophthalmologic service presented a positive influence on consumer
      loyalty and WOM. However, managers in Ophthalmology can successfully use
      experimental marketing strategies if they promote a story, meaning a life
      experience.

PMID- 29450403
TI  - Iris juvenile xanthogranuloma in an infant - spontaneous hyphema and secondary
      glaucoma.
AB  - Juvenile xanthogranuloma (JXG) is a benign histiocytic skin disorder mainly
      encountered during infancy and childhood. Although with multiple potential
      localizations, less than 1% of the cases exhibit ocular manifestations. Some of
      these might lead to serious complications, specifically, secondary glaucoma that
      can result in severe and blinding eye disease. The aim of the present case report
      was to demonstrate typical clinical features, emphasize the difficulties
      attributed when managing these patients and literature review. We present the
      case of 4 months old female baby with spontaneous hyphema and secondary
      unilateral glaucoma due to ocular JXG. The natural history and treatment of the
      condition were extremely difficult to handle due to multiple opinions in
      histopathology related to other severe conditions that resembled with the lesions
      detected in this case: myelomonocytic leukemia and Langerhans cell histiocytosis.
      Although a minority of patients with JXG have ocular involvement, recognition of
      this condition is important because a treatment delay can lead to serious
      complications, such as glaucoma and spontaneous hyphema, as in our case. A
      thorough differential diagnosis represents the key to a proper management plan in
      these patients, both on short and long term. "Triple disease" defined as JXG plus
      neurofibromatosis type 1 (NF-1) and juvenile chronic myelogenous leukemia (JCML)
      has been reported, but it was not confirmed in our patient.

PMID- 29450404
TI  - Reengineering deep brain stimulation for movement disorders: Emerging
      technologies.
AB  - Deep brain stimulation (DBS) is a neurosurgical technique, which consists of
      continuous delivery of an electrical pulse through chronically implanted
      electrodes connected to a neurostimulator, programmable in amplitude, pulse
      width, frequency, and stimulation channel. DBS is a promising treatment option
      for addressing severe and drug-resistant movement disorders. The success of DBS
      therapy is a combination of surgical implantation techniques, device technology,
      and clinical programming strategies. Changes in device settings require highly
      trained and experienced clinicians to achieve maximal therapeutic benefit for
      each targeted symptom, and optimization of stimulation parameters can take many
      visits. Thus, the development of innovative DBS technologies that can optimize
      the clinical implementation of DBS will lead to wider scale utilization. This
      review aims to present engineering approaches that have the potential to improve
      clinical outcomes of DBS, focusing on the development novel temporal patterns,
      innovative electrode designs, computational models to guide stimulation, closed
      loop DBS, and remote programming.

PMID- 29450405
TI  - Building with intent: technologies and principles for engineering mammalian cell
      based therapies to sense and respond.
AB  - The engineering of cells as programmable devices has enabled therapeutic
      strategies that could not otherwise be achieved. Such strategies include
      recapitulating and enhancing native cellular functions and composing novel
      functions. These novel functions may be composed using both natural and
      engineered biological components, with the latter exemplified by the development
      of synthetic receptor and signal transduction systems. Recent advances in
      implementing these approaches include the treatment of cancer, where the most
      clinical progress has been made to date, and the treatment of diabetes.
      Principles for engineering cell-based therapies that are safe and effective are
      increasingly needed and beginning to emerge, and will be essential in the
      development of this new class of therapeutics.

PMID- 29450406
TI  - Chemical Modification of the siRNA Seed Region Suppresses Off-Target Effects by
      Steric Hindrance to Base-Pairing with Targets.
AB  - Chemical modifications of 2'-O-methyl (2'-OMe) and locked nucleic acid (LNA) of
      the nucleotides in the seed region (positions 2-8) of the small interfering RNA
      (siRNA) guide strand significantly reduced seed-matched (SM) off-target effects.
      The siRNA with 2'-OMe modifications inhibited the expression of a completely
      matched (CM) target gene, whereas that with LNA modifications did not inhibit the
      expression of the CM target. By computational predictions of conformational
      changes of siRNA by these modifications, we revealed that both modifications in
      the siRNA seed region reduce SM off-target effects by steric hindrance to base
      pairing with target transcripts but LNA modifications also disturb the
      association of the siRNA guide strand with the Argonaute (AGO) protein by
      altering RNA conformation. Thus, chemical modifications of the siRNA guide
      strand, which alter steric conformation to disturb base-pairing with target
      transcripts but do not disturb the association with the AGO protein, may
      successfully suppress off-target effects without substantial loss of RNA
      silencing activity.

PMID- 29450407
TI  - Changes in the Cardiac GHSR1a-Ghrelin System Correlate With Myocardial
      Dysfunction in Diabetic Cardiomyopathy in Mice.
AB  - Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a),
      are present in cardiac tissue. Activation of GHSR1a by ghrelin promotes
      cardiomyocyte contractility and survival, and changes in myocardial GHSR1a and
      circulating ghrelin track with end-stage heart failure, leading to the hypothesis
      that GHSR1a is a biomarker for heart failure. We hypothesized that GHSR1a could
      also be a biomarker for diabetic cardiomyopathy (DCM). We used two models of
      streptozotocin (STZ)-induced DCM: group 1, adult mice treated with 35 mg/kg STZ
      for 3 days; and group 2, neonatal mice treated with 70 mg/kg STZ at days 2 and 5
      after birth. In group 1, mild fasting hyperglycemia (11 mM) was first detected 8
      weeks after the last injection, and in group 2, severe fasting hyperglycemia (20
      mM) was first detected 1 to 3 weeks after the last injection. In group 1, left
      ventricular function was slightly impaired as measured by echocardiography, and
      Western blot analysis showed a significant decrease in myocardial GHSR1a. In
      group 2, GHSR1a levels were also decreased as assessed by Cy5-ghrelin(1-19)
      fluorescence microscopy, and there was a significant negative correlation between
      GHSR1a levels and glucose tolerance. There were significant positive correlations
      between GHSR1a and ghrelin and between GHSR1a and sarcoplasmic reticulum Ca2+
      ATPase 2a (SERCA2a), a marker for contractility, but not between GHSR1a and B
      type natriuretic peptide, a marker for heart failure. We conclude that the
      subclinical stage of DCM is accompanied by alterations in the myocardial ghrelin
      GHSR1a system, suggesting the possibility of a biomarker for DCM.

PMID- 29450408
TI  - Effect of Arginase-1 Inhibition on the Incidence of Autoimmune Diabetes in NOD
      Mice.
AB  - Metabolism of the amino acid L-arginine is implicated in many physiological and
      pathophysiological processes including autoimmune conditions such as type 1
      diabetes (T1D). Alternate arginine metabolism through the citrulline-nitric oxide
      (NO) or the ornithine pathways can lead to proinflammatory or immune regulatory
      effects, respectively. In this report, we blocked the arginine-ornithine
      metabolic pathway by inhibiting the enzyme arginase-1 with Nomega-hydroxy-nor
      arginine (nor-NOHA) to make arginine more available to the alternate citrulline
      pathway for augmented NO production and increased incidence of autoimmune T1D in
      female non-obese diabetic (NOD) mice. Unexpectedly, mice receiving nor-NOHA did
      not develop diabetes although increased NO production is proinflammatory and
      expected to increase diabetes incidence. These results warrant further studies of
      the mechanism of action of nor-NOHA, and highlight its potential as a therapeutic
      agent for the treatment or prevention of T1D.

PMID- 29450410
TI  - Catalyst-free one step synthesis of large area vertically stacked N-doped
      graphene-boron nitride heterostructures from biomass source.
AB  - A procedure for the one-step preparation of films of few-layer N-doped graphene
      on top of nanometric hexagonal boron nitride sheets ((N)graphene/h-BN) based on
      the pyrolysis at 900  degrees C under an inert atmosphere of a film of chitosan
      containing about 20 wt% of ammonium borate salt as a precursor is reported.
      During the pyrolysis a spontaneous segregation of (N)graphene and boron nitride
      layers takes place. The films were characterized by optical microscopy that shows
      a thin graphene overlayer covering the boron nitride layer, the latter showing
      characteristic cracks, and by XPS measurements at different monitoring angles
      from 0 degrees  to 50 degrees  where an increase in the proportion of C vs. B and
      N was observed. The resulting (N)graphene/h-BN films were also characterized by
      Raman, HRTEM, SEM, FIB-SEM and AFM. The thickness of the (N)graphene and h-BN
      layers can be controlled by varying the concentration of precursors and the spin
      coating rate and is typically below 5 nm. Electrical conductivity measurements
      using microelectrodes can cause the burning of the graphene layer at high
      intensities, while lower intensities show that (N)graphene/h-BN films behave as
      capacitors in the range of positive voltages.

PMID- 29450409
TI  - Microstructurally Anchored Cardiac Kinematics by Combining In Vivo DENSE MRI and
      cDTI.
AB  - Metrics of regional myocardial function can detect the onset of cardiovascular
      disease, evaluate the response to therapy, and provide mechanistic insight into
      cardiac dysfunction. Knowledge of local myocardial microstructure is necessary to
      distinguish between isotropic and anisotropic contributions of local deformation
      and to quantify myofiber kinematics, a microstructurally anchored measure of
      cardiac function. Using a computational model we combine in vivo cardiac
      displacement and diffusion tensor data to evaluate pointwise the deformation
      gradient tensor and isotropic and anisotropic deformation invariants. In
      discussing the imaging methods and the model construction, we identify potential
      improvements to increase measurement accuracy. We conclude by demonstrating the
      applicability of our method to compute myofiber strain in five healthy
      volunteers.

PMID- 29450411
TI  - Revalorization of wild Asparagus stipularis Forssk. as a traditional vegetable
      with nutritional and functional properties.
AB  - The nutritional values and phytochemical composition of young shoots of wild
      Asparagus stipularis Forssk. from Tunisia were determined in this study. The
      antioxidant (tested by four different in vitro assays) and antiproliferative
      properties (against human tumour cell lines) of aqueous and hydroalcoholic
      extracts of the young shoots were also investigated. The obtained results
      indicated that the young shoots are a potential source of valuable nutrients and
      dietary fiber, and their hydroalcoholic extract showed marked antioxidant and
      antiproliferative activities in all tested assays. The major phenolic compound,
      characterized by using a high-performance liquid chromatograph coupled with diode
      array and mass spectrometer detectors, in both extracts was diferuloyl glycerol.
      Our results reinforce the interest in recovering the traditional culinary uses of
      this wild plant, with potential functional properties, which can be included in
      the modern diet as an alternative to the variety of vegetables normally used.

PMID- 29450412
TI  - Clinically approved liposomal nanomedicines: lessons learned from the
      biomolecular corona.
AB  - Nowadays, liposomes are the most successful drug delivery systems with a dozen
      drug products available in the clinic. Grafting poly-(ethylene glycol) (PEG) onto
      the liposome surface prevents protein binding thus prolonging blood circulation,
      while synthetic modification of the terminal PEG molecule with ligands (e.g.
      monoclonal antibodies and peptides) should promote selective accumulation in the
      tumor region with respect to healthy tissues. However, despite big efforts,
      advances have not outgrown the development stage and just a few targeted
      liposomal drugs are commercially available. The latest studies have clarified
      that following exposure to physiological environments liposomes are covered by a
      biomolecular corona (BC). Main factors shaping the BC are the liposomes'
      physicochemical properties (i.e. size, surface charge and lipid composition), the
      biological fluid (e.g. plasma of healthy volunteers vs. plasma of cancer
      patients) and environmental factors (e.g. temperature). Combining the most recent
      evidence reported in the literature, herein we suggest that the liposome-BC could
      act as a personalized "endogenous trigger" affecting off-target interactions and
      controlling the indication for disease of clinically approved formulations. In
      this Opinion paper, we suggest that a better understanding of the liposome-BC
      together with improvements in mapping corona proteins will open the fascinating
      possibility to manipulate the BC by liposome design. This is not an easy task,
      but it could represent a turning point in the development of novel liposome-based
      targeting strategies for personalized nanomedicines.

PMID- 29450413
TI  - Polyelectrolyte scaling laws for microgel yielding near jamming.
AB  - Micro-scale hydrogel particles, known as microgels, are used in industry to
      control the rheology of numerous different products, and are also used in
      experimental research to study the origins of jamming and glassy behavior in soft
      sphere model systems. At the macro-scale, the rheological behaviour of densely
      packed microgels has been thoroughly characterized; at the particle-scale,
      careful investigations of jamming, yielding, and glassy-dynamics have been
      performed through experiment, theory, and simulation. However, at low packing
      fractions near jamming, the connection between microgel yielding phenomena and
      the physics of their constituent polymer chains has not been made. Here we
      investigate whether basic polymer physics scaling laws predict macroscopic
      yielding behaviours in packed microgels. We measure the yield stress and cross
      over shear-rate in several different anionic microgel systems prepared at packing
      fractions just above the jamming transition, and show that our data can be
      predicted from classic polyelectrolyte physics scaling laws. We find that
      diffusive relaxations of microgel deformation during particle re-arrangements can
      predict the shear-rate at which microgels yield, and the elastic stress
      associated with these particle deformations predict the yield stress.

PMID- 29450414
TI  - First-principles method for calculating the rate constants of internal-conversion
      and intersystem-crossing transitions.
AB  - A method for calculating the rate constants for internal-conversion (kIC) and
      intersystem-crossing (kISC) processes within the adiabatic and Franck-Condon (FC)
      approximations is proposed. The applicability of the method is demonstrated by
      calculation of kIC and kISC for a set of organic and organometallic compounds
      with experimentally known spectroscopic properties. The studied molecules were
      pyrromethene-567 dye, psoralene, hetero[8]circulenes, free-base porphyrin,
      naphthalene, and larger polyacenes. We also studied fac-Alq3 and fac-Ir(ppy)3,
      which are important molecules in organic light emitting diodes (OLEDs). The
      excitation energies were calculated at the multi-configuration quasi-degenerate
      second-order perturbation theory (XMC-QDPT2) level, which is found to yield
      excitation energies in good agreement with experimental data. Spin-orbit coupling
      matrix elements, non-adiabatic coupling matrix elements, Huang-Rhys factors, and
      vibrational energies were calculated at the time-dependent density functional
      theory (TDDFT) and complete active space self-consistent field (CASSCF) levels.
      The computed fluorescence quantum yields for the pyrromethene-567 dye, psoralene,
      hetero[8]circulenes, fac-Alq3 and fac-Ir(ppy)3 agree well with experimental data,
      whereas for the free-base porphyrin, naphthalene, and the polyacenes, the
      obtained quantum yields significantly differ from the experimental values,
      because the FC and adiabatic approximations are not accurate for these molecules.

PMID- 29450415
TI  - Selective light driven reduction of CO2 to HCOOH in water using a {MoV9}n (n =
      1332-3600) based soft-oxometalate (SOM).
AB  - A soft-oxometalate (SOM) based on Mo and V i.e. {MoV9} in their highest oxidation
      state reduces CO2 to HCOOH selectively in water. Catalysis initiates without the
      use of any photosensitizer and solvent water acts as the sacrificial electron
      donor which gets oxidized to generate oxygen. Electrons and protons released in
      this process reduce CO2 to HCOOH.

PMID- 29450416
TI  - A G-quadruplex motif at the 3' end of sgRNAs improves CRISPR-Cas9 based genome
      editing efficiency.
AB  - Originating as a component of prokaryotic adaptive immunity, the type II
      CRISPR/Cas9 system has been repurposed for targeted genome editing in various
      organisms. Although Cas9 can bind and cleave DNA efficiently under in vitro
      conditions, its activity inside a cell can vary dramatically between targets
      owing to the differences between genomic loci and the availability of enough
      Cas9/sgRNA (single guide RNA) complex molecules for cleavage. Most methods have
      so far relied on Cas9 protein engineering or base modifications in the sgRNA
      sequence to improve CRISPR/Cas9 activity. Here we demonstrate that a structure
      based rational design of sgRNAs can enhance the efficiency of Cas9 cleavage in
      vivo. By appending a naturally forming RNA G-quadruplex motif to the 3' end of
      sgRNAs we can improve its stability and target cleavage efficiency in zebrafish
      embryos without inducing off-target activity, thereby underscoring its value in
      the design of better and optimized genome editing triggers.

PMID- 29450417
TI  - Enhanced magnetic and thermoelectric properties in epitaxial polycrystalline
      SrRuO3 thin films.
AB  - Transition metal oxide thin films show versatile electric, magnetic, and thermal
      properties which can be tailored by deliberately introducing macroscopic grain
      boundaries via polycrystalline solids. In this study, we focus on the
      modification of magnetic and thermal transport properties by fabricating single-
      and polycrystalline epitaxial SrRuO3 thin films using pulsed laser epitaxy. Using
      the epitaxial stabilization technique with an atomically flat polycrystalline
      SrTiO3 substrate, an epitaxial polycrystalline SrRuO3 thin film with the
      crystalline quality of each grain comparable to that of its single-crystalline
      counterpart is realized. In particular, alleviated compressive strain near the
      grain boundaries due to coalescence is evidenced structurally, which induced the
      enhancement of ferromagnetic ordering of the polycrystalline epitaxial thin film.
      The structural variations associated with the grain boundaries further reduce the
      thermal conductivity without deteriorating the electronic transport, and lead to
      an enhanced thermoelectric efficiency in the epitaxial polycrystalline thin
      films, compared with their single-crystalline counterpart.

PMID- 29450418
TI  - Distinct photophysical behaviour and transport of cell-impermeable
      [Ru(bpy)2dppz]2+ in live cells using cucurbit[7]uril as a delivery system.
AB  - Here, we report the delivery of a cell-impermeable [Ru(bpy)2dppz]2+ complex
      across a cell membrane using a cucurbit[7]uril molecular container. Encapsulation
      of complex 1 in the cucurbit[7]uril cavity showed an 830-fold enhancement in the
      luminescence intensity of the non-emissive complex in aqueous solution. This
      molecular light-switch effect stems from the incorporation of the dppz ligand of
      1 inside the CB7 cavity and can be attributed to long range coulombic forces
      between Ru2+ and the carbonyl portal of CB7 via CHO interactions. This is
      reflected in the 1H-NMR experiments, and further corroborated by theoretical
      calculations.

PMID- 29450419
TI  - Small size yet big action: a simple sulfate anion templated a discrete 78
      nuclearity silver sulfur nanocluster with a multishell structure.
AB  - A discrete 78-nucleus silver-sulfur nanocluster with a sulfate-centered
      multishell structure was isolated and characterized. Its crystal structure
      revealed 18 and 60 Ag atoms in the inner and outer shell, respectively. The inner
      shell of 18-nuclearity Ag atoms is a very rare convex polyhedron featuring an
      elongated triangular orthobicupola. The incorporation of a sulfate anion and
      multishell arrangement in the nanocluster led to a dramatic decrease in the band
      gap (Eg = 1.40 eV). Our study showed that simple anions can also induce the
      formation of high-nuclearity silver clusters with excellent optical properties.

PMID- 29450420
TI  - Characterization of the influences of morphology on the intrinsic properties of
      perovskite films by temperature-dependent and time-resolved spectroscopies.
AB  - Organic-inorganic halide perovskites have attracted enormous attention owing to
      their promising application in photovoltaic devices. The morphology of the
      perovskites is the key to driving the performance of perovskite devices, which
      necessitates a systematic study. In this work, two typical morphologies, i.e.,
      flake and cube, of perovskite films are fabricated, and the temperature-dependent
      optical absorption and photoluminescence properties of the two types of
      perovskite film are systematically investigated. From the temperature-dependent
      spectra, both exciton and phase transition temperatures of the flake film are
      found to be about 10 K lower than those of the cube one. Meanwhile, the
      influences of the morphology on the exciton binding energy, optical phonon energy
      and polaron binding energy are quantitatively characterized. The exciton binding
      of the flake film is nearly three times smaller than that of the cube one, while
      the phonon coupling energy and the polaron binding energy of the former are about
      5 meV and 2 meV larger than those of the latter. Furthermore, the results of
      photoluminescence lifetime and charge separation efficiency further reveal that
      the charge carrier kinetics in the two kinds of perovskite films is significantly
      different. The current study provides a theoretical framework to understand the
      fundamental physics of perovskites and to promote the design and enhancement of
      active materials for improved optoelectronic devices.

PMID- 29450421
TI  - In situ atomic force microscopy study of nano-micro sodium deposition in ester
      based electrolytes.
AB  - We report an in situ analysis of nano-micro sodium deposition in an ester-based
      electrolyte using atomic force microscopy. It is found that sodium dendrites are
      effectively suppressed by adding fluoroethylene carbonate (FEC) as an electrolyte
      additive. The decomposition of FEC provides a NaF-containing solid electrolyte
      interphase with homogenous morphology and high modulus, leading to stable sodium
      deposition and high Coulombic efficiency (88% over 50 cycles) of the sodium metal
      anode.

PMID- 29450422
TI  - Remarkable structural effects on the complexation of actinides with H
      phosphonates: a combined experimental and quantum chemical study.
AB  - The structural effects of the carbon chain on the extraction of actinides by
      organo-phosphorus extractants have been examined experimentally and by
      computation. Branched butyl H-phosphonates and their linear chain isomer, n-butyl
      H-phosphonate (DBHP), were synthesised and characterised using IR, NMR and GC-MS
      techniques. Their physical properties viz. viscosity, density and aqueous
      solubility have been examined. DBHP, Di-iso-butyl H phosphonate (DiBHP) and Di
      sec-butyl H phosphonate (DsBHP) were employed for the extraction of uranium and
      americium ions from nitric acid. 233U (alpha-tracer) and 241Am (gamma-tracer)
      were employed as representative isotopes for the extraction of U and Am,
      respectively, and their distribution ratios (D) were obtained as a function of
      nitric acid concentration (0.01-8 M). Branching of the alkyl chain at the
      secondary carbon atom showed unexpected neutral extractant behaviour for DsBHP
      which is generally classified as an acidic extractant. The acid-dependent dual
      extraction mechanisms for the H-phosphonates have been examined both
      experimentally and through quantum chemical calculations. This dramatic effect
      can be partly attributed to the hindrance in the formation of the enol tautomer
      through the strengthening of the P[double bond, length as m-dash]OH hydrogen
      bonding in the DsBHP extractant. Density functional theory (DFT) based
      calculations were carried out to understand the complexation behaviour of
      actinides with the two extractants. Possible structures and binding affinities of
      actinides with H-phosphonates have been deduced from electronic structure
      calculations. Finally, the trends in distribution ratios were additionally
      explored and correlated with experimental observations for both metal ions.

PMID- 29450423
TI  - Kinetics and mechanism of the chromium(vi) catalyzed decomposition of
      hypochlorous acid at elevated temperature and high ionic strength.
AB  - An important reaction step in the industrial production of NaClO3
      (electrochemical chlorate process) is the thermal decomposition of HOCl/OCl- to
      yield ClO3- and Cl-. It is widely accepted that this reaction is accelerated by
      aqueous chromium(vi) species. A detailed kinetic study was conducted under
      industrially relevant conditions, i.e. at high ionic strength (6.0 M) and
      elevated temperature (80  degrees C), to investigate this phenomenon. The
      decomposition of hypochlorous acid was followed in the presence of Cr(vi) or
      phosphate (PO43-) or without any additive. In addition to the beneficial pH
      buffering effect of Cr(vi), the CrO42- form of chromium(vi) was found to slightly
      catalyze the decomposition of hypochlorous acid. The overall rate of HOCl
      decomposition can be expressed as -dcHOCl/dt = kdec[HOCl]2[OCl-] +
      kcat[HOCl]2[CrO42-]. The corresponding rate constants were determined, kdec = 9.4
      +/- 0.1 M-2 s-1 and kcat = 4.6 +/- 0.8 M-2 s-1, and mechanistic interpretation of
      the catalytic rate law is given. The contribution of the catalytic path to the
      overall rate of decomposition changes from ca. 30% at pH = 8 to ca. 70% at pH =
      6.

PMID- 29450425
TI  - In situ growth of all-inorganic perovskite nanocrystals on black phosphorus
      nanosheets.
AB  - This communication describes a novel low-dimensional nanohybrid structure
      consisting of all-inorganic perovskite nanocrystals (NCs) growing in situ on two
      dimensional (2D) black phosphorus (BP) nanosheets. Such a nanohybrid structure
      promises synergetic properties by combining the respective strengths of
      perovskite materials and BP, which opens new opportunities for next-generation
      optoelectronic devices.

PMID- 29450426
TI  - Concentrated solar light for rapid crystallization of nanomaterials and extreme
      enhancement of photoelectrochemical performance.
AB  - In this communication, a concentrated solar light (CSL) annealing strategy is
      proposed with a Fresnel lens as the concentrator for rapid and effective
      crystallization of nanomaterials. More interestingly, the CSL can be integrated
      into photoelectrochemical devices and achieved an unprecedented photocurrent
      density.

PMID- 29450424
TI  - CD44v6 increases gastric cancer malignant phenotype by modulating adipose stromal
      cell-mediated ECM remodeling.
AB  - CD44, an abundantly expressed adhesion molecule, and its alternative splice
      variants have been associated with tumorigenesis and metastasis. In the context
      of gastric cancer (GC), de novo expression of CD44 variant 6 (CD44v6) is found in
      more than 60% of GCs, but its role in the pathogenesis and progression of this
      type of cancer remains unclear. Using a combination of media conditioning
      experiments and decellularized extracellular matrices (ECMs), this study
      investigates the hypothesis that CD44v6 overexpression enhances tumor cell
      malignant behavior by modulating stromal cell-mediated ECM remodeling. Our
      findings indicate that soluble factors secreted by CD44v6 expressing GC cells
      particularly increase proliferation and myofibroblastic differentiation of
      adipose stromal cells (ASCs). These changes in ASC phenotype mediate the
      deposition of fibrotic/desmoplastic ECM that, in turn, stimulates GC
      proliferation and inhibits GC clustering. Pharmacological inhibition of matrix
      metalloproteinase (MMP) activity in tumor cells abrogated matrix-induced changes
      in tumor cell malignant behavior. Additionally, studies in mice confirmed the
      pathological relevance of CD44v6 expression and consequential changes in ECM
      remodeling to gastric tumorigenesis in vivo. Collectively, these results indicate
      a direct link between CD44v6, ECM remodeling, and GC malignant behavior opening
      new insights into potential CD44v6-targeted therapies.

PMID- 29450427
TI  - Performance enhancement of carbon nanotube thin film transistor by yttrium oxide
      capping.
AB  - Carbon nanotube thin film transistors (CNT-TFTs) are regarded as promising
      technology for active matrix pixel driving circuits of future flat panel displays
      (FPD). For FPD application, unipolar thin film transistors (TFTs) with high
      mobility (MU), high on-state current (ION), low off-current (IOFF) at high
      source/drain bias and small hysteresis are required simultaneously. Though
      excellent values of those performance metrics have been realized individually in
      different reports, the overall performance of previously reported CNT-TFTs has
      not met the above requirements. In this paper, we found that yttrium oxide (Y2O3)
      capping is helpful in improving both ION and MU of CNT-TFTs. Combining Y2O3
      capping and Al2O3 passivation, unipolar CNT-TFTs with high ION/IOFF (>107) and
      low IOFF (~pA) at -10.1 V source/drain bias, and relatively small hysteresis in
      the range of -30 V to +30 V gate voltage were achieved, which are capable of
      active matrix display driving.

PMID- 29450428
TI  - Dynamics of bridge-loop transformation in a membrane with mixed monolayer/bilayer
      structures.
AB  - Instead of forming a typical bilayer or monolayer membrane, both the bridge (I
      shape) and loop (U-shape) conformations coexist in the planar membranes formed by
      ABA triblock copolymers in a selective solvent. The non-equilibrium and
      equilibrium relaxation dynamics of polymer conformations are monitored. The non
      equilibrium relaxation time depends on the initial composition and increases with
      an increase in the immiscibility between A and B blocks. The equilibrium
      composition of the loop-shape polymer is independent of the initial composition
      and A-B immiscibility. However, the extent of equilibrium composition
      fluctuations subsides as the A and B blocks become highly incompatible. The
      influences of the A-B immiscibility on the geometrical, mechanical, and transport
      properties of the membrane have also been investigated. As the immiscibility
      increases, the overall membrane thickness and the B block layer thickness (h)
      increase because of the increment in the molecular packing density. As a result,
      both the stretching (KA) and bending (KB) moduli grow significantly with the
      increasing A-B immiscibility. Consistent with the case of typical membranes, the
      ratio KB/KAh2 = 2 * 10-3 is a constant. Although the lateral diffusivity of
      polymers is insensitive to immiscibility, the membrane permeability decreases
      substantially as the A-B immiscibility is increased.

PMID- 29450429
TI  - Palladium-catalyzed silaborative carbocyclizations of 1,6-diynes.
AB  - An addition/cyclization reaction of 1,6-diynes was developed for the synthesis of
      highly substituted 1,2-dialkylidenecycloalkanes. In this work, 1,6-diynes reacted
      with (dimethylphenylsilyl)pinacol-borane in the presence of a palladium catalyst
      to afford 1,2-dialkylidenecycloalkanes bearing silyl and boryl groups with a
      (Z,Z)-configuration in good to excellent yields. Moreover, the corresponding
      products could be easily converted into other synthetically useful compounds.
      This protocol provides an efficient and practical method of heteroelement-element
      linkage addition to the unsaturated 1,6-diynes.

PMID- 29450430
TI  - Facile synthesis of a cationic-doped [Ca24Al28O64]4+(4e-) composite via a rapid
      citrate sol-gel method.
AB  - One of the greatest challenges in the enhancement of the electrical properties of
      conductive mayenite [Ca24Al28O64]4+(4e-) (hereinafter C12A7:e-) is the design of
      a more suitable/simple synthesis strategy that can be employed to obtain the
      required properties such as excellent stable electrical conductivity, a high
      electron concentration, outstanding mobility, and an exceptionally large surface
      area. Therefore, to synthesize C12A7:e- in the metallic state, we proposed a
      facile, direct synthesis strategy based on an optimized sol-gel combustion method
      under a nitrogen gas environment using the low-cost precursors Ca(NO3)2.4H2O and
      Al(NO3)3.9H2O. Using this developed strategy, we successfully synthesized
      moderately conductive nanoscale C12A7:e- powder, but with unexpected carbon
      components (reduced graphene oxide (rGO) and/or graphene oxide (GO)). The
      synthesized C12A7:e- composite at room temperature has an electrical conductivity
      of about 21 S cm-1, a high electron concentration of approximately 1.5 * 1021 cm
      3, and a maximum specific surface area of 265 m2 g-1. Probably, the synthesized
      rGO was coated on nanocage C12A7:e- particles. In general, the C12A7:e- electride
      is sensitive to the environment (especially to oxygen and moisture) and protected
      by an rGO coating on C12A7:e- particles, which also enhances the mobility and
      keeps the conductivity of C12A7:e- electride stable over a long period. Doped
      mayenite electride exhibits a conductivity that is strongly dependent on the
      substitution level. The conductivity of gallium-doped mayenite electride
      increases with the doping level and has a maximum value of 270 S cm-1, which for
      the first time has been reported for the stable C12A7:e- electride. In the case
      of Si-substituted calcium aluminate, the conductivity has a maximum value of 222
      S cm-1 at room temperature.

PMID- 29450431
TI  - Gas-phase kinetics modifies the CCN activity of a biogenic SOA.
AB  - Our current knowledge of cloud condensation nuclei (CCN) activity and the
      hygroscopicity of secondary organic aerosol (SOA) depends on the particle size
      and composition, explicitly, the thermodynamic properties of the aerosol solute
      and subsequent interactions with water. Here, we examine the CCN activation of 3
      SOA systems (2 biogenic single precursor and 1 mixed precursor SOA system) in
      relation to gas-phase decay. Specifically, the relationship between time, gas
      phase precursor decay and CCN activity of 100 nm SOA is studied. The studied SOA
      systems exhibit a time-dependent growth of CCN activity at an instrument
      supersaturation of ~0.2%. As such, we define a critical activation time, t50,
      above which a 100 nm SOA particle will activate. The critical activation time for
      isoprene, longifolene and a mixture of the two precursor SOA is 2.01 hours, 2.53
      hours and 3.17 hours, respectively. The activation times are then predicted with
      gas-phase kinetic data inferred from measurements of precursor decay. The gas
      phase prediction of t50 agrees well with CCN measured t50 (within 0.05 hours of
      the actual critical times) and suggests that the gas-to-particle phase
      partitioning may be more significant for SOA CCN prediction than previously
      thought.

PMID- 29450432
TI  - Tracing the sources of PCDD/Fs in Baltic Sea air by using metals as source
      markers.
AB  - The atmosphere is the major contributor of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) in the Baltic Sea environment. In this study, we
      investigated the potential of using metals along with PCDD/Fs as markers of
      important emission sources of PCDD/Fs in air. The air concentrations of PCDD/F
      congeners (n = 17), other persistent organic pollutants (n = 8) and metals (n =
      16) were determined in summer and winter air using high volume samplers at a
      rural field station (Aspvreten, Sweden) located close to the Baltic Sea coast.
      During winter, PCDD/F levels were on average 20 times higher than in summer (5.1
      +/- 5.8 fg toxicity equivalents (TEQ) m-3 and 0.26 +/- 0.18 fg TEQ m-3,
      respectively) mostly due to a higher fraction of PCDFs. The increased levels of
      PCDD/Fs were pronounced mainly in air masses that had travelled from southern (S)
      and eastern (E) compass sectors. A principal component analysis (PCA) of metal
      levels in Scots pine (Pinus sylvestris) needles sampled to reflect various air
      emission source types helped to identify potential marker metals for selected
      known atmospheric emission sources of PCDD/Fs and to rank among the candidate
      source types. Brown coal burning, domestic burning and heavy oil burning appeared
      to be the source types that contribute most of the PCDD/Fs in Baltic Sea air. The
      current study demonstrates a successful approach for source tracing of PCDD/Fs in
      air, where integrated indices from seasonal and spatial patterns of PCDD/Fs as
      well as metal source markers were used to trace and rank sources.

PMID- 29450433
TI  - A novel 3-D cuprous iodide polymer with a high Cu/I ratio.
AB  - A novel 3-D cuprous iodide polymer [CuI(MU6-L)]n with a Cu/I ratio as high as 3
      (1, H2L = 1,3-bis(2H-tetrazol-5-yl)benzene) has been hydrothermally synthesized.
      The 3-D framework of 1 is constructed by the linkages of rare 1-D cationic
      aggregates [CuI2+]n and anionic bi-tetrazolate bridges. 1 shows unusually
      thermochromic luminescent and photocatalytic properties, and its density
      functional theory calculation has also been studied.

PMID- 29450434
TI  - Direct sequential C-H iodination/organoyl-thiolation for the benzenoid A-ring
      modification of quinonoid deactivated systems: a new protocol for potent
      trypanocidal quinones.
AB  - We report a sequential C-H iodination/organoyl-thiolation of naphthoquinones and
      their relevant trypanocidal activity. Under a combination of AgSR with a copper
      source, sulfur-substituted benzenoid quinones were prepared in high yields
      (generally >90%). This provides an efficient and general method for preparing A
      ring modified naphthoquinoidal systems, recognized as a challenge in quinone
      chemistry.

PMID- 29450435
TI  - Reversible phase transition and switchable dielectric behaviors triggered by
      rotation and order-disorder motions of crowns.
AB  - Solid-to solid-state reversible phase transitions are widely used in switchable
      dielectrics, ferroelectrics, piezoelectrics, and pyroelectric and non-linear
      optical materials. Herein we report a new crown ether clathrate, [Habf-(18-crown
      6)1.5]+ [PF6]- (Habf = p-ammonium benzene formamide) which shows an interesting
      reversible phase transition near room temperature (263 K). X-ray single crystal
      diffraction analysis shows that the synergetic rotation motion between the 18
      crown-6 crown ethers and the order-disorder motions of both hexafluorophosphate
      guest anions and 18-crown-6 crown ether host molecules lead to the phase
      transition. This reversible phase transition is confirmed by an evident thermal
      anomaly behavior around 263 K. The apparent step-like dielectric change around
      the phase transition indicates that it has potential application in dielectric
      switches.

PMID- 29450436
TI  - Palladium-catalyzed synthesis of quinolin-2(1H)-ones: the unexpected reactivity
      of azodicarboxylate.
AB  - Quinolin-2(1H)-one is a useful structure unit present in a wide range of natural
      products and pharmaceuticals. A Pd(ii)-catalyzed synthesis of quinolin-2(1H)-ones
      from quinoline N-oxides was developed with azodicarboxylates which act as both
      the activating agent and oxidant. The reaction proceeded under mild conditions
      and no protection against air and moisture was needed.

PMID- 29450437
TI  - Efficient selection methods for black phosphorene nanoribbons.
AB  - Black phosphorene (BP) has shown anisotropic, electronic, mechanical, and thermal
      properties for various promising applications in recent years. To take full
      advantage of this unique anisotropy in its further functional design and
      application, it is of paramount importance to separate BP with well-defined
      chirality quickly and precisely. In this paper, we propose three efficient
      methods to separate BP ribbons with different chiralities by utilizing their
      strong chirality-dependent bending stiffness. Our results show that the bending
      stiffness in the zigzag direction is 4 times larger than that in the armchair
      direction. The mechanical anisotropy and bending-binding competition are used to
      realize chirality-dependent design. To fold, wrap or scroll the BP nanoribbons,
      it is necessary to overcome the bending stiffness by applying the binding energy
      between the BP nanoribbons and the contact surfaces. Due to the mechanical
      anisotropy, the BP nanoribbons could easily be folded, wrapped and scrolled along
      the armchair direction rather than the zigzag direction. Therefore, we introduce
      this characteristic in our chirality separation designs as, the self-folding
      model to fold up the armchair BP nanoribbons by nanoparticles, the suspension
      bridge sieve model to pull down the armchair BP nanoribbons, and the nanorod
      roller model to scroll up the armchair nanoribbons. Our separation methods in
      this research can be extended to other 2D materials with anisotropic mechanical
      properties. We hope our findings would offer a novel route for the manufacturing
      of BP-based electronic devices and self-assembly of nano-devices.

PMID- 29450438
TI  - The mechanism of manganese dissolution on Li1.6Mn1.6O4 ion sieves with HCl.
AB  - Li1.6Mn1.6O4 is a representative ion sieve material that is used to recover
      lithium from salt brines and bitterns owing to its high lithium ion adsorption
      capacity reaching 11.9-44 mg g-1. However, manganese dissolution during acid
      treatment hinders the industrial application of the material. For investigating
      the mechanism of manganese dissolution, the precursor Li1.6Mn1.6O4 and ion sieve
      H1.6Mn1.6O4 were prepared and characterized using X-ray diffraction (XRD),
      scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT
      IR), chemical content analyses, diffuse reflectance infrared Fourier-transform
      spectroscopy (DRIFTS), and X-ray photoelectron spectroscopy (XPS). The results of
      XRD, SEM, and FT-IR showed that the bulk phase of Li1.6Mn1.6O4 retained the
      spinel structure, whereas the lattice diminished during acid treatment. The
      results of chemical content analyses showed that the bulk phase of Li1.6Mn1.6O4
      contained a few trivalent manganese atoms and that the mean valence of manganese
      in the material increased during acid treatment. DRIFTS and XPS exhibited that
      the surface of Li1.6Mn1.6O4 was mostly full of tetravalent manganese and retained
      the spinel structure during acid treatment. In the proposed mechanism of
      manganese dissolution, an electron of trivalent manganese in the bulk phase
      transfers to the surface and is captured by tetravalent manganese within the
      acidic environment. Then, tetravalent manganese is converted to bivalent
      manganese after acquiring sufficient electrons, and dissolution occurs
      simultaneously.

PMID- 29450439
TI  - Synergistic palladium/copper-catalyzed Csp3-Csp2 cross-couplings using aldehydes
      as latent alpha-alkoxyalkyl anion equivalents.
AB  - The first Csp3-Csp2 cross-coupling using aldehydes as latent alpha-alkoxyalkyl
      anion equivalents has been achieved. The synergistic palladium/copper-catalyzed
      reaction of aromatic aldehydes and aryl bromides with a silylboronate afforded
      the three-component coupling products, silyl-protected benzhydrol derivatives.
      The reaction pathway involves the catalytic formation of a nucleophilic alpha
      silyloxybenzylcopper(i) species followed by its palladium-catalyzed cross
      coupling with aryl bromides.

PMID- 29450440
TI  - Injection molded lab-on-a-disc platform for screening of genetically modified E.
      coli using liquid-liquid extraction and surface enhanced Raman scattering.
AB  - We present the development of an automated centrifugal microfluidic platform with
      integrated sample pre-treatment (filtration and liquid-liquid extraction) and
      detection (SERS-based sensing). The platform consists of eight calibration and
      four assay modules, fabricated with polypropylene using injection molding and
      bonded with ultrasonic welding. The platform was used for detection of a
      secondary bacterial metabolite (p-coumaric acid) from bacterial supernatant. The
      obtained extraction efficiency was comparable to values obtained in batch
      experiments and the SERS-based sensing showed a good correlation with HPLC
      analysis.

PMID- 29450441
TI  - Failures of Sacral Neuromodulation for Incontinence.

PMID- 29450442
TI  - Gray-Brown Patches on the Face of a 62-Year-Old Woman.

PMID- 29450444
TI  - Error in Author Listing.

PMID- 29450443
TI  - Postincarceration Fatal Overdoses After Implementing Medications for Addiction
      Treatment in a Statewide Correctional System.

PMID- 29450445
TI  - Lenalidomide as an Alternative to Thalidomide for Treatment of Recurrent Erythema
      Multiforme.

PMID- 29450446
TI  - Association Between Mental Health Status and Patient Satisfaction With the
      Functional Outcomes of Rhinoplasty.
AB  - Importance: Mental health can have an impact on patient satisfaction with
      rhinoplasty. However, the association between mental health and patient
      satisfaction with functional outcomes of rhinoplasty is poorly understood.
      Objective: To determine whether preoperative mental health is associated with
      satisfaction with functional outcomes of rhinoplasty. Design, Setting, and
      Participants: This case-control study assessed baseline nasal function and
      postsurgical functional outcomes for 88 consecutive patients undergoing
      rhinoplasty with both cosmetic and functional goals at 2 tertiary rhinologic
      centers in Sydney, Australia. Exposures: Poor mental well-being was defined
      preoperatively by the Optum SF-36v2 Health Survey mental component summary. Main
      Outcomes and Measures: Nasal function was assessed with patient-reported outcome
      measures, including visual analog scales, the Nasal Obstruction Symptom
      Evaluation Scale (NOSE), the 22-item Sinonasal Outcome Test (SNOT-22), and Likert
      scales. Objective outcomes included nasal peak inspiratory flow, nasal airway
      resistance, and minimum cross-sectional area. All outcomes were assessed
      preoperatively and 6 months postoperatively. The 36-item Optum SF-36v2 Health
      Survey mental component summary was used to assess mental well-being, with a
      score of less than 40 indicating poor mental well-being and a score 40 or higher
      indicating normal well-being. Results: Mean (SD) patient age was 37.6 (12.9)
      years and 53 of 88 (60.2%) were women. The mental component summary defined
      impaired well-being in n = 24 (cases) and normal well-being in n = 64 (controls).
      There were improvements in the total study population across most nasal function
      outcomes and in both groups. After rhinoplasty, benefit was seen for both groups
      in visual analog scale (left side mean [SD] change, 18 [30]; P < .001 and right
      side mean [SD] change, 24 [30]; P < .001); NOSE (mean [SD] change, 1.35 [1.21]; P
      < .001); and SNOT-22 (mean [SD] change, 0.81 [0.88]; P < .001) scores. Nasal peak
      inspiratory flow improved for both groups (mean [SD] change, 32 [45] L/min; P <
      .001), while nasal airway resistance and minimum cross-sectional area remained
      similar (change in nasal airway resistance, 0.086 Pa/cm3/s; 95% CI, -0.007
      Pa/cm3/s to 0.179 Pa/cm3/s and change in minimum cross-sectional area, -0.04 cm2;
      95% CI, -0.21 cm2 to 0.13 cm2). Patients with poor mental health had similar
      improvements in nasal function compared with controls. Conclusions and Relevance:
      Rhinoplasty imparts similar benefits to nasal function assessed by patient
      reported outcome measures and objective airflow measures regardless of
      preoperative mental health status. Level of Evidence: 3.

PMID- 29450448
TI  - Diagnosis uPGrade-Advances in Pyoderma Gangrenosum.

PMID- 29450449
TI  - Error in Key Points and Conclusions.

PMID- 29450450
TI  - Technique to Repair Total Septal Perforation With a Pericranial Flap: The Money
      Box Approach.

PMID- 29450451
TI  - Oregon's Death With Dignity Act.

PMID- 29450447
TI  - Interplay Among Psychopathologic Variables, Personal Resources, Context-Related
      Factors, and Real-life Functioning in Individuals With Schizophrenia: A Network
      Analysis.
AB  - Importance: Enhanced understanding of factors associated with symptomatic and
      functional recovery is instrumental to designing personalized treatment plans for
      people with schizophrenia. To date, this is the first study using network
      analysis to investigate the associations among cognitive, psychopathologic, and
      psychosocial variables in a large sample of community-dwelling individuals with
      schizophrenia. Objective: To assess the interplay among psychopathologic
      variables, cognitive dysfunctions, functional capacity, personal resources,
      perceived stigma, and real-life functioning in individuals with schizophrenia,
      using a data-driven approach. Design, Setting, and Participants: This
      multicenter, cross-sectional study involved 26 university psychiatric clinics
      and/or mental health departments. A total of 921 community-dwelling individuals
      with a DSM-IV diagnosis of schizophrenia who were stabilized on antipsychotic
      treatment were recruited from those consecutively presenting to the outpatient
      units of the sites between March 1, 2012, and September 30, 2013. Statistical
      analysis was conducted between July 1 and September 30, 2017. Main Outcomes and
      Measures: Measures covered psychopathologic variables, neurocognition, social
      cognition, functional capacity, real-life functioning, resilience, perceived
      stigma, incentives, and service engagement. Results: Of 740 patients (221 women
      and 519 men; mean [SD] age, 40.0 [10.9] years) with complete data on the 27 study
      measures, 163 (22.0%) were remitted (with a score of mild or better on 8 core
      symptoms). The network analysis showed that functional capacity and everyday life
      skills were the most central and highly interconnected nodes in the network.
      Psychopathologic variables split in 2 domains, with positive symptoms being one
      of the most peripheral and least connected nodes. Functional capacity bridged
      cognition with everyday life skills; the everyday life skills node was connected
      to disorganization and expressive deficits. Interpersonal relationships and work
      skills were connected to avolition; the interpersonal relationships node was also
      linked to social competence, and the work skills node was linked to social
      incentives and engagement with mental health services. A case-dropping bootstrap
      procedure showed centrality indices correlations of 0.75 or greater between the
      original and randomly defined samples up to 481 of 740 case-dropping (65.0%). No
      difference in the network structure was found between men and women. Conclusions
      and Relevance: The high centrality of functional capacity and everyday life
      skills in the network suggests that improving the ability to perform tasks
      relevant to everyday life is critical for any therapeutic intervention in
      schizophrenia. The pattern of network node connections supports the
      implementation of personalized interventions.

PMID- 29450454
TI  - Toward a National Surgical Strategy for Type 2 Diabetes Resolution: Can We Do
      Better?

PMID- 29450452
TI  - Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term
      Outcomes Among Patients With Localized High-Risk Soft Tissue Sarcoma: The EORTC
      62961-ESHO 95 Randomized Clinical Trial.
AB  - Importance: Patients with soft tissue sarcoma are at risk for local recurrence
      and distant metastases despite optimal local treatment. Preoperative
      anthracycline plus ifosfamide chemotherapy improves outcome in common
      histological subtypes. Objective: To analyze whether the previously reported
      improvement in local progression-free survival by adding regional hyperthermia to
      neoadjuvant chemotherapy translates into improved survival. Design, Setting, and
      Participants: Open-label, phase 3 randomized clinical trial to evaluate the
      efficacy and toxic effects of neoadjuvant chemotherapy plus regional
      hyperthermia. Adult patients (age >=18 years) with localized soft tissue sarcoma
      (tumor >=5 cm, French Federation Nationale des Centers de Lutte Contre le Cancer
      [FNCLCC] grade 2 or 3, deep) were accrued across 9 centers (6, Germany; 1,
      Norway; 1, Austria; 1, United States) from July 1997 to November 2006. Follow-up
      ended December 2014. Interventions: After stratification for tumor presentation
      and site, patients were randomly assigned to either neoadjuvant chemotherapy
      consisting of doxorubicin, ifosfamide, and etoposide alone, or combined with
      regional hyperthermia. Main Outcomes and Measures: The primary end point was
      local progression-free survival. Secondary end points included treatment safety
      and survival, with survival defined from date of randomization to death due to
      disease or treatment. Patients lost to follow-up were censored at the date of
      their last follow-up. Results: A total of 341 patients were randomized, and 329
      (median [range] age, 51 [18-70] years; 147 women, 182 men) were eligible for the
      intention-to-treat analysis. By December 2014, 220 patients (67%; 95% CI, 62%
      72%) had experienced disease relapse, and 188 (57%; 95% CI, 52%-62%) had died.
      Median follow-up was 11.3 years. Compared with neoadjuvant chemotherapy alone,
      adding regional hyperthermia improved local progression-free survival (hazard
      ratio [HR], 0.65; 95% CI, 0.49-0.86; P = .002). Patients randomized to
      chemotherapy plus hyperthermia had prolonged survival rates compared with those
      randomized to neoadjuvant chemotherapy alone (HR, 0.73; 95% CI, 0.54-0.98; P =
      .04) with 5-year survival of 62.7% (95% CI, 55.2%-70.1%) vs 51.3% (95% CI, 43.7%
      59.0%), respectively, and 10-year survival of 52.6% (95% CI, 44.7%-60.6%) vs
      42.7% (95% CI, 35.0%-50.4%). Conclusions and Relevance: Among patients with
      localized high-risk soft tissue sarcoma the addition of regional hyperthermia to
      neoadjuvant chemotherapy resulted in increased survival, as well as local
      progression-free survival. For patients who are candidates for neoadjuvant
      treatment, adding regional hyperthermia may be warranted. Trial Registration:
      clinicaltrials.gov Identifier: NCT00003052.

PMID- 29450453
TI  - The Association of Age With Clinical Presentation and Comorbidities of Pyoderma
      Gangrenosum.
AB  - Importance: Pyoderma gangrenosum is an inflammatory neutrophilic dermatosis.
      Current knowledge of this rare disease is limited owing to a lack of validated
      diagnostic criteria and large population studies. Objective: To evaluate the
      association of age with the clinical presentation and comorbidities of pyoderma
      gangrenosum. Design, Setting, and Participants: This was a multicenter
      retrospective cohort study performed at tertiary academic referral centers in
      urban settings. Adults (>=18 years) who were evaluated and diagnosed as having
      pyoderma gangrenosum at the Brigham and Women's and Massachusetts General
      Hospitals from 2000 to 2015 and the University of Pennsylvania Health System from
      2006 to 2016 were included. Main Outcomes and Measures: Patient demographics,
      clinical features, medical comorbidities, and treatment. Results: Of the 356
      validated cases of pyoderma gangrenosum included in the study, 267 (75%) were
      women and 284 (84.8%) were white. The mean (SD) age at presentation was 51.6
      (17.7) years. Pathergy was recorded in 100 patients (28.1%). A total of 238
      patients (66.9%) had associated medical comorbidities: inflammatory bowel disease
      in 146 patients (41.0%); inflammatory arthritis in 73 patients (20.5%); solid
      organ malignant neoplasms in 23 patients (6.5%); hematologic malignant neoplasms
      in 21 patients (5.9%); and hematologic disorders, specifically monoclonal
      gammopathy of undetermined significance, myelodysplastic syndrome, and
      polycythemia vera in 17 patients (4.8%). When stratified by age, pathergy was
      more common in patients 65 years or older (36.3% vs 24.3%; P = .02). Inflammatory
      bowel disease was the only medical comorbidity that was more common in patients
      younger than 65 years (47.7% vs 26.6%; P < .001), while a number of medical
      comorbidities were more common in those 65 years or older, including rheumatoid
      arthritis (13.3% vs 6.2%; P = .03), ankylosing spondylitis (1.8% vs 0%; P = .04),
      solid organ malignant neoplasms (13.3% vs 3.3%; P < .001), hematologic malignant
      neoplasms (9.7% vs 4.1%; P = .04), and the aforementioned hematologic disorders
      (10.6% vs 2.1%; P < .001). Conclusions and Relevance: Although clinical
      presentation in this large cohort was similar between different age groups,
      disease associations varied by age. The findings of this study may allow for a
      more focused, age-specific evaluation of patients with pyoderma gangrenosum.

PMID- 29450455
TI  - Oregon's Death With Dignity Act-Reply.

PMID- 29450456
TI  - Is There a Future for Ovarian Cancer Screening?

PMID- 29450457
TI  - Language Matters-Dermatologists Should Speak Out Against a Word Ban at Centers
      for Disease Control and Prevention.

PMID- 29450458
TI  - Errors in Data Presentation, Funding, and Acknowledgments.

PMID- 29450459
TI  - Technological Advances, Biologic Rationales, and the Associated Success of
      Chemotherapy With Hyperthermia in Improved Outcomes in Patients With Sarcoma.

PMID- 29450460
TI  - How Rare Is Too Rare Not to Care?

PMID- 29450461
TI  - Hip Fracture and Palpitations in a 92-Year-Old Woman With Bronchiectasis.

PMID- 29450463
TI  - New Statistical Editor-January 2018.

PMID- 29450464
TI  - Evaluating Readmission-Need for More Clarity on Methods.

PMID- 29450462
TI  - Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the
      United States.
AB  - Importance: No US national data are available on the prevalence and correlates of
      DSM-5-defined major depressive disorder (MDD) or on MDD specifiers as defined in
      DSM-5. Objective: To present current nationally representative findings on the
      prevalence, correlates, psychiatric comorbidity, functioning, and treatment of
      DSM-5 MDD and initial information on the prevalence, severity, and treatment of
      DSM-5 MDD severity, anxious/distressed specifier, and mixed-features specifier,
      as well as cases that would have been characterized as bereavement in DSM-IV.
      Design, Setting, and Participants: In-person interviews with a representative
      sample of US noninstitutionalized civilian adults (>=18 years) (n = 36 309) who
      participated in the 2012-2013 National Epidemiologic Survey on Alcohol and
      Related Conditions III (NESARC-III). Data were collected from April 2012 to June
      2013 and were analyzed in 2016-2017. Main Outcomes and Measures: Prevalence of
      DSM-5 MDD and the DSM-5 specifiers. Odds ratios (ORs), adjusted ORs (aORs), and
      95% CIs indicated associations with demographic characteristics and other
      psychiatric disorders. Results: Of the 36 309 adult participants in NESARC-III,
      12-month and lifetime prevalences of MDD were 10.4% and 20.6%, respectively. Odds
      of 12-month MDD were significantly lower in men (OR, 0.5; 95% CI, 0.46-0.55) and
      in African American (OR, 0.6; 95% CI, 0.54-0.68), Asian/Pacific Islander (OR,
      0.6; 95% CI, 0.45-0.67), and Hispanic (OR, 0.7; 95% CI, 0.62-0.78) adults than in
      white adults and were higher in younger adults (age range, 18-29 years; OR, 3.0;
      95% CI, 2.48-3.55) and those with low incomes ($19 999 or less; OR, 1.7; 95% CI,
      1.49-2.04). Associations of MDD with psychiatric disorders ranged from an aOR of
      2.1 (95% CI, 1.84-2.35) for specific phobia to an aOR of 5.7 (95% CI, 4.98-6.50)
      for generalized anxiety disorder. Associations of MDD with substance use
      disorders ranged from an aOR of 1.8 (95% CI, 1.63-2.01) for alcohol to an aOR of
      3.0 (95% CI, 2.57-3.55) for any drug. Most lifetime MDD cases were moderate
      (39.7%) or severe (49.5%). Almost 70% with lifetime MDD had some type of
      treatment. Functioning among those with severe MDD was approximately 1 SD below
      the national mean. Among 12.9% of those with lifetime MDD, all episodes occurred
      just after the death of someone close and lasted less than 2 months. The
      anxious/distressed specifier characterized 74.6% of MDD cases, and the mixed
      features specifier characterized 15.5%. Controlling for severity, both specifiers
      were associated with early onset, poor course and functioning, and suicidality.
      Conclusions and Relevance: Among US adults, DSM-5 MDD is highly prevalent,
      comorbid, and disabling. While most cases received some treatment, a substantial
      minority did not. Much remains to be learned about the DSM-5 MDD specifiers in
      the general population.

PMID- 29450465
TI  - Pediatric-Inspired Treatment Regimens for Adolescents and Young Adults With
      Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: A Review.
AB  - Importance: The incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic
      lymphoma (LBL) in adolescent and young adult (AYA) patients (age range, 15-39
      years) in the United States is increasing at a greater rate than in younger or
      older persons. Their optimal treatment has been increasingly debated as pediatric
      regimens have become more widely used in the age group. This review compares the
      basic features of pediatric and adult chemotherapy regimens for ALL and LBL,
      recognizes and describes the challenges of the pediatric regimen, and suggests
      strategies to facilitate its adoption for AYAs with ALL and LBL. Observations:
      All but 2 of 25 published comparisons of outcomes with pediatric and adult
      regimens for ALL and LBL in AYAs and 1 meta-analysis favor the pediatric regimen.
      After more than a half-century of clinical trials of the pediatric regimens,
      including at least 160 phase 3 trials in the United States, the pediatric
      regimens have become far more complex than most adult regimens. Asparaginase, a
      critical component of the pediatric regimens, is more difficult to administer to
      AYAs (and older patients) but nonetheless has a favorable benefit to toxicity
      ratio for AYAs. A dramatic reduction in outcome of ALL and LBL during the AYA
      years (the "survival cliff") is coincident with similar reductions in proportions
      of AYAs referred to academic centers and enrolled on clinical trials (the
      "accrual cliff" and "referral cliff"). Conclusions and Relevance: The
      accumulating data increasingly support treating AYAs with ALL and LBL with a
      pediatric-inspired regimen or an approved institutional or national clinical
      trial tailored for this patient group. A need to develop clinical trials
      specifically for AYAs and to encourage their participation is paramount, with a
      goal to improve both the quantity and quality of survival.

PMID- 29450467
TI  - The Danger of Applying the ProtecT Trial to Minority Populations.

PMID- 29450466
TI  - Diagnostic Criteria of Ulcerative Pyoderma Gangrenosum: A Delphi Consensus of
      International Experts.
AB  - Importance: Pyoderma gangrenosum is a rare inflammatory skin condition that is
      difficult to diagnose. Currently, it is a "diagnosis of exclusion," a definition
      not compatible with clinical decision making or inclusion for clinical trials.
      Objective: To propose and validate diagnostic criteria for ulcerative pyoderma
      gangrenosum. Evidence Review: Diagnostic criteria were created following a Delphi
      consensus exercise using the RAND/UCLA Appropriateness Method. The criteria were
      validated against peer-reviewed established cases of pyoderma gangrenosum and
      mimickers using k-fold cross-validation with methods of multiple imputation.
      Findings: Delphi exercise yielded 1 major criterion-biopsy of ulcer edge
      demonstrating neutrophilic infiltrate-and 8 minor criteria: (1) exclusion of
      infection; (2) pathergy; (3) history of inflammatory bowel disease or
      inflammatory arthritis; (4) history of papule, pustule, or vesicle ulcerating
      within 4 days of appearing; (5) peripheral erythema, undermining border, and
      tenderness at ulceration site; (6) multiple ulcerations, at least 1 on an
      anterior lower leg; (7) cribriform or "wrinkled paper" scar(s) at healed ulcer
      sites; and (8) decreased ulcer size within 1 month of initiating
      immunosuppressive medication(s). Receiver operating characteristic analysis
      revealed that 4 of 8 minor criteria maximized discrimination, yielding
      sensitivity and specificity of 86% and 90%, respectively. Conclusions and
      Relevance: This Delphi exercise produced 1 major criterion and 8 minor criteria
      for the diagnosis of ulcerative pyoderma gangrenosum. The criteria may serve as a
      guideline for clinicians, allowing for fewer misdiagnoses and improved patient
      selection for clinical trials.

PMID- 29450468
TI  - Activity and Safety of Cetuximab Plus Modified FOLFOXIRI Followed by Maintenance
      With Cetuximab or Bevacizumab for RAS and BRAF Wild-type Metastatic Colorectal
      Cancer: A Randomized Phase 2 Clinical Trial.
AB  - Importance: The combination of a triple-drug chemotherapy regimen with an anti
      epidermal growth factor receptor (EGFR) agent as a first-line treatment of
      metastatic colorectal cancer (mCRC) showed promising activity along with safety
      concerns in single-arm phase 2 trials. The role of maintenance following
      chemotherapy and anti-EGFR and the optimal regimen to be adopted are not
      established. Objectives: To evaluate the activity and safety of cetuximab plus
      modified FOLFOXIRI (mFOLFOXIRI) and explore the role of maintenance with
      cetuximab or bevacizumab in RAS and BRAF wild-type mCRC. Design, Setting, and
      Participants: In a prospective, noncomparative, open-label, multicenter,
      randomized phase 2 trial, patients aged 18 to 75 years with unresectable,
      previously untreated RAS and BRAF wild-type (before amendment, KRAS wild-type)
      mCRC were recruited from 21 oncology units in Italy from October 19, 2011, to
      March 1, 2015 (followed up through May 31, 2017). In total, 323 patients were
      screened and 143 were randomized to 2 treatment arms to receive as a first-line
      induction a regimen of mFOLFOXIRI plus cetuximab followed by cetuximab (arm A) or
      bevacizumab (arm B) until disease progression. Primary analyses were conducted in
      a modified intention-to-treat population. Interventions: mFOLFOXIRI plus
      cetuximab repeated every 2 weeks for up to 8 cycles, followed by maintenance with
      cetuximab or bevacizumab until disease progression. Main Outcomes and Measures:
      The primary end point was the 10-month progression-free rate (PFR); secondary end
      points included progression-free and overall survival, response rate, rate of
      metastases resection, and adverse events. Results: Of 143 patients randomized,
      116 (81.1%) (median [interquartile range (IQR)] age, 59.5 [53-67] years; 34
      [29.3%] women) had RAS and BRAF wild-type mCRC. At a median (IQR) follow-up of
      44.0 (30.5-52.1) months, 10-month PFRs were 50.8% (90% CI, 39.5%-62.2%) in arm A
      and 40.4% (90% CI, 29.4%-52.1%) in arm B. The overall response rate was 71.6%
      (95% CI, 62.4%-79.5%). Main grade 3/4 adverse events were neutropenia (occurring
      in 36 patients [31%]), diarrhea (in 21 patients [18%]), skin toxic effects (in 18
      patients [16%]), asthenia (in 11 patients [9%]), stomatitis (in 7 patients [6%]),
      and febrile neutropenia (in 3 patients [3%]). Conclusions and Relevance: Although
      neither of the 2 arms met the primary end point, the findings indicate that a 4
      month induction regimen of mFOLFOXIRI plus cetuximab is feasible and provides
      relevant activity results, leading to a high surgical resection rate. Trial
      Registration: clinicaltrials.gov Identifier: NCT02295930.

PMID- 29450469
TI  - Association Between Bariatric Surgery and Rates of Continuation, Discontinuation,
      or Initiation of Antidiabetes Treatment 6 Years Later.
AB  - Importance: Few large-scale long-term prospective cohort studies have assessed
      changes in antidiabetes treatment after bariatric surgery. Objective: To describe
      the association between bariatric surgery and rates of continuation,
      discontinuation, or initiation of antidiabetes treatment 6 years after bariatric
      surgery compared with a matched control obese group. Design, Setting, and
      Participants: This nationwide observational population-based cohort study
      extracted health care reimbursement data from the French national health
      insurance database from January 1, 2008, to December 31, 2015. All patients
      undergoing primary bariatric surgery in France between January 1 and December 31,
      2009, were matched on age, sex, body mass index category, and antidiabetes
      treatment with control patients hospitalized for obesity in 2009 with no
      bariatric surgery between 2005 and 2015. Exposures: Bariatric surgery, including
      adjustable gastric banding (AGB), gastric bypass (GBP), and sleeve gastrectomy
      (SG). Main Outcome and Measure: Reimbursement for antidiabetes drugs. Mixed
      effects logistic regression models estimated factors of discontinuation or
      initiation of antidiabetes treatment over a period of 6 years. Results: In 2009,
      a total of 15 650 patients (mean [SD] age, 38.9 [11.2] years; 84.6% female; 1633
      receiving antidiabetes treatment) underwent primary bariatric surgery, with 48.5%
      undergoing AGB, 27.7% undergoing GBP, and 22.0% undergoing SG. Among patients
      receiving antidiabetes treatment at baseline, the antidiabetes treatment
      discontinuation rate was higher 6 years after bariatric surgery than in controls
      (-49.9% vs -9.0%, P < .001). In multivariable analysis, the main predictive
      factors for discontinuation were the following: GBP (odds ratio [OR], 16.7; 95%
      CI, 13.0-21.4), SG (OR, 7.30; 95% CI, 5.50-9.50), and AGB (OR, 4.30; 95% CI, 3.30
      5.60) compared with no bariatric surgery, as well as insulin use (OR, 0.17; 95%
      CI, 0.13-0.22), dual therapy without insulin (OR, 0.38; 95% CI, 0.32-0.45) vs
      monotherapy, lipid-lowering treatment (OR, 0.76; 95% CI, 0.63-0.91),
      antidepressant treatment (OR, 0.67; 95% CI, 0.55-0.81), and age (OR, 0.96; 95%
      CI, 0.95-0.97) per year. For patients without antidiabetes treatment at baseline,
      the 6-year antidiabetes treatment initiation rate was much lower after bariatric
      surgery than in controls (1.4% vs 12.0%, P < .001). In multivariable analysis,
      protective factors were GBP (OR, 0.06; 95% CI, 0.04-0.09), SG (OR, 0.08; 95% CI,
      0.06-0.11), and AGB (OR, 0.16; 95% CI, 0.14-0.20) vs controls, and risk factors
      were as follows: body mass index category (OR, 2.04; 95% CI, 1.68-2.47 for >=50.0
      vs 30.0-39.9 and OR, 1.68; 95% CI, 1.49-1.90 for 40.0-49.9 vs 30.0-39.9),
      antihypertensive treatment (OR, 1.49; 95% CI, 1.33-1.67), low income (OR, 1.43;
      95 % CI, 1.26-1.62), and age (OR, 1.04; 95 % CI, 1.03-1.05) per year. Conclusions
      and Relevance: Bariatric surgery was associated with a significantly higher 6
      year postoperative antidiabetes treatment discontinuation rate compared with
      baseline and with an obese control group without bariatric surgery.

PMID- 29450470
TI  - Incidence of Delayed Intracranial Hemorrhage in Older Patients After Blunt Head
      Trauma.
AB  - Importance: Current guidelines conflict on the management of older adults who
      have blunt head trauma taking anticoagulant and antiplatelet medications. This is
      partially due to the limited data comparing patients who are taking these
      medications with those who are not. Objective: To investigate the incidence of
      delayed traumatic intracranial hemorrhage in older adults with head trauma,
      including those taking anticoagulant and antiplatelet medications. Design,
      Setting, and Participants: This prospective observational cohort study included
      patients 55 years and older who had blunt head trauma and were transported via
      emergency medical services between August 1, 2015, and September 30, 2016. The
      setting was a multicenter study conducted at 11 hospitals in northern California.
      Patients were excluded if they had traumatic intracranial hemorrhage on the
      initial cranial computed tomographic scan, did not have a cranial computed
      tomographic scan performed at the initial emergency department visit, refused
      consent for a follow-up telephone call, or did not have reliable means of follow
      up. Main Outcome and Measure: The primary outcome of this study was the incidence
      of delayed traumatic intracranial hemorrhage within 14 days of injury. Results:
      Among 859 patients enrolled in the study, the median age was 75 years
      (interquartile range, 64-85 years), and 389 (45.3%) were male. A total of 343
      patients (39.9%) were taking an anticoagulant or antiplatelet medication. Three
      patients (0.3%; 95% CI, 0.1%-1.0%) had a delayed traumatic intracranial
      hemorrhage. Of the 3 patients, 1 of 75 patients (1.3%; 95% CI, 0.0%-7.2%) who
      were taking warfarin sodium alone and 2 of 516 patients (0.4%; 95% CI, 0.1%-1.4%)
      who were not taking any anticoagulant or antiplatelet medication had a delayed
      traumatic intracranial hemorrhage. Thirty-nine patients (4.5%; 95% CI, 3.2%-6.2%)
      were lost to follow-up. Conclusions and Relevance: Overall, the incidence of
      delayed intracranial hemorrhage in older adults who have blunt head trauma is
      low, including patients taking an anticoagulant or antiplatelet medication. These
      findings suggest that routine observation and serial cranial computed tomography
      may not be necessary in these patients.

PMID- 29450472
TI  - Otorhinolaryngology and Diving-Part 1: Otorhinolaryngological Hazards Related to
      Compressed Gas Scuba Diving: A Review.
AB  - Importance: Scuba diving is becoming increasingly popular. However, scuba diving
      is associated with specific risks; 80% of adults and 85% of juvenile divers (aged
      6-17 years) have been reputed to have an ear, nose, or throat complaint related
      to diving at some point during their diving career. Divers frequently seek advice
      from primary care physicians, diving physicians, and otorhinolaryngologists, not
      only in the acute setting, but also related to the long-term effects of diving.
      Observations: The principles underpinning diving-related injuries that may
      present to the otorhinolaryngologist rely on gas volume and gas saturation laws,
      and the prevention of these injuries requires both that the diver is skilled and
      that their anatomy allows for pressure equalization between the various
      anatomical compartments. The overlapping symptoms of middle ear barotrauma, inner
      ear barotrauma, and inner ear decompression sickness can cause a diagnostic
      conundrum, and a thorough history of both the diver's symptoms and the dive
      itself are required to elucidate the diagnosis. Correct diagnosis and appropriate
      treatment result in a more timely return to safe diving. Conclusions and
      Relevance: The aim of this review is to provide a comprehensive overview of
      otorhinolaryngological complications during diving. With the increasing
      popularity of diving and the frequency of ear, nose, or throat-related injuries,
      it could be expected that these injuries will become more common and this review
      provides a resource for otorhinolaryngologists to diagnose and treat these
      conditions.

PMID- 29450471
TI  - Association of Childhood Infection With IQ and Adult Nonaffective Psychosis in
      Swedish Men: A Population-Based Longitudinal Cohort and Co-relative Study.
AB  - Importance: Associations between childhood infection, IQ, and adult nonaffective
      psychosis (NAP) are well established. However, examination of sensitive periods
      for exposure, effect of familial confounding, and whether IQ provides a link
      between childhood infection and adult NAP may elucidate pathogenesis of psychosis
      further. Objectives: To test the association of childhood infection with IQ and
      adult NAP, to find whether shared familial confounding explains the infection-NAP
      and IQ-NAP associations, and to examine whether IQ mediates and/or moderates the
      childhood infection-NAP association. Design, Setting, and Participants:
      Population-based longitudinal cohort study using linkage of Swedish national
      registers. The risk set included all Swedish men born between 1973 and 1992 and
      conscripted into the military until the end of 2010 (n = 771 698). We included
      647 515 participants in the analysis. Measurement of Exposures: Hospitalization
      with any infection from birth to age 13 years. Main Outcomes and Measures:
      Hospitalization with an International Classification of Diseases diagnosis of NAP
      until the end of 2011. At conscription around age 18 years, IQ was assessed for
      all participants. Results: At the end of follow-up, the mean (SD) age of
      participants was 30.73 (5.3) years. Exposure to infections, particularly in early
      childhood, was associated with lower IQ (adjusted mean difference for infection
      at birth to age 1 year: -1.61; 95% CI, -1.74 to -1.47) and with increased risk of
      adult NAP (adjusted hazard ratio for infection at birth to age 1 year: 1.19; 95%
      CI, 1.06 to 1.33). There was a linear association between lower premorbid IQ and
      adult NAP, which persisted after excluding prodromal cases (adjusted hazard ratio
      per 1-point increase in IQ: 0.976; 95% CI, 0.974 to 0.978). The infection-NAP and
      IQ-NAP associations were similar in the general population and in full-sibling
      pairs discordant for exposure. The association between infection and NAP was both
      moderated (multiplicative, beta = .006; SE = 0.002; P = .02 and additive, beta =
      .008; SE = 0.002; P = .001) and mediated (beta = .028; SE = 0.002; P < .001) by
      IQ. Childhood infection had a greater association with NAP risk in the lower,
      compared with higher, IQ range. Conclusions and Relevance: Early childhood is a
      sensitive period for the effects of infection on IQ and NAP. The associations of
      adult NAP with early-childhood infection and adolescent IQ are not fully
      explained by shared familial factors and may be causal. Lower premorbid IQ in
      individuals with psychosis arises from unique environmental factors, such as
      early-childhood infection. Early-childhood infections may increase the risk of
      NAP by affecting neurodevelopment and by exaggerating the association of
      cognitive vulnerability with psychosis.

PMID- 29450474
TI  - Visual Field Progression Is More Complicated Than Meets the Eye.

PMID- 29450473
TI  - Elevated Blood Viscosity and Microrecirculation Resulting From Coronary Stent
      Malapposition.
AB  - One particular complexity of coronary artery is the natural tapering of the
      vessel with proximal segments having larger caliber and distal tapering as the
      vessel get smaller. The natural tapering of a coronary artery often leads to
      proximal incomplete stent apposition (ISA). ISA alters coronary hemodynamics and
      creates pathological path to develop complications such as in-stent restenosis,
      and more worryingly, stent thrombosis (ST). By employing state-of-the-art
      computer-aided design software, generic stent hoops were virtually deployed in an
      idealized tapered coronary artery with decreasing malapposition distance.
      Pulsatile blood flow simulations were carried out using computational fluid
      dynamics (CFD) on these computer-aided design models. CFD results reveal
      unprecedented details in both spatial and temporal development of
      microrecirculation environments throughout the cardiac cycle (CC). Arterial
      tapering also introduces secondary microrecirculation. These primary and
      secondary microrecirculations provoke significant fluctuations in arterial wall
      shear stress (WSS). There has been a direct correlation with changes in WSS and
      the development of atherosclerosis. Further, the presence of these
      microrecirculations influence strongly on the local levels of blood viscosity in
      the vicinity of the malapposed stent struts. The observation of secondary
      microrecirculations and changes in blood rheology is believed to complement the
      wall (-based) shear stress, perhaps providing additional physical explanations
      for tissue accumulation near ISA detected from high resolution optical coherence
      tomography (OCT).

PMID- 29450475
TI  - A Woman With Confusion and Blurred Vision.

PMID- 29450477
TI  - Cellular Response to Cyclic Compression of Tissue Engineered Intervertebral Disk
      Constructs Composed of Electrospun Polycaprolactone.

PMID- 29450476
TI  - More Questions Raised by Concussion-like Symptoms Found in US Diplomats Who
      Served in Havana.

PMID- 29450478
TI  - Hard Swelling on Inner Cheek.

PMID- 29450479
TI  - Open Access-Is There a Predator at the Door?

PMID- 29450480
TI  - The Yet Unrealized Promise of Ovarian Cancer Screening.

PMID- 29450481
TI  - Messengers of Truth and Health-Young Artists of Color Raise Their Voices to
      Prevent Diabetes.

PMID- 29450482
TI  - Potential Confounders in an Investigation of the Vision-Related Functional Burden
      of Diabetic Retinopathy.

PMID- 29450483
TI  - Implementation Research: Embracing Practitioners' Views.
AB  - Purpose: This research explores practitioners' perspectives during the
      implementation of triadic gaze intervention (TGI), an evidence-based protocol for
      assessing and planning treatment targeting gaze as an early signal of intentional
      communication for young children with physical disabilities. Method: Using
      qualitative methods, 7 practitioners from 1 early intervention center reported
      their perceptions about (a) early intervention for young children with physical
      disabilities, (b) acceptability and feasibility in the use of the TGI protocol in
      routine practice, and (c) feasibility of the TGI training. Qualitative data were
      gathered from 2 semistructured group interviews, once before and once after TGI
      training and implementation. Results: Qualitative results documented the
      practitioners' reflections on recent changes to early intervention service
      delivery, the impact of such change on TGI adoption, and an overall strong
      enthusiasm for the TGI protocol, despite some need for adaptation. Conclusion:
      These results are discussed relative to adapting the TGI protocol and training,
      when considering how to best bring about change in practice. More broadly,
      results highlighted the critical role of researcher-practitioner collaboration in
      implementation research and the value of qualitative data for gaining a richer
      understanding of practitioners' perspectives about the implementation process.

PMID- 29450485
TI  - Error in Funding/Support.

PMID- 29450484
TI  - Neurological Manifestations Among US Government Personnel Reporting Directional
      Audible and Sensory Phenomena in Havana, Cuba.
AB  - Importance: From late 2016 through August 2017, US government personnel serving
      on diplomatic assignment in Havana, Cuba, reported neurological symptoms
      associated with exposure to auditory and sensory phenomena. Objective: To
      describe the neurological manifestations that followed exposure to an unknown
      energy source associated with auditory and sensory phenomena. Design, Setting,
      and Participants: Preliminary results from a retrospective case series of US
      government personnel in Havana, Cuba. Following reported exposure to auditory and
      sensory phenomena in their homes or hotel rooms, the individuals reported a
      similar constellation of neurological symptoms resembling brain injury. These
      individuals were referred to an academic brain injury center for
      multidisciplinary evaluation and treatment. Exposures: Report of experiencing
      audible and sensory phenomena emanating from a distinct direction (directional
      phenomena) associated with an undetermined source, while serving on US government
      assignments in Havana, Cuba, since 2016. Main Outcomes and Measures: Descriptions
      of the exposures and symptoms were obtained from medical record review of
      multidisciplinary clinical interviews and examinations. Additional objective
      assessments included clinical tests of vestibular (dynamic and static balance,
      vestibulo-ocular reflex testing, caloric testing), oculomotor (measurement of
      convergence, saccadic, and smooth pursuit eye movements), cognitive
      (comprehensive neuropsychological battery), and audiometric (pure tone and speech
      audiometry) functioning. Neuroimaging was also obtained. Results: Of 24
      individuals with suspected exposure identified by the US Department of State, 21
      completed multidisciplinary evaluation an average of 203 days after exposure.
      Persistent symptoms (>3 months after exposure) were reported by these individuals
      including cognitive (n = 17, 81%), balance (n = 15, 71%), visual (n = 18, 86%),
      and auditory (n = 15, 68%) dysfunction, sleep impairment (n = 18, 86%), and
      headaches (n = 16, 76%). Objective findings included cognitive (n = 16, 76%),
      vestibular (n = 17, 81%), and oculomotor (n = 15, 71%) abnormalities. Moderate to
      severe sensorineural hearing loss was identified in 3 individuals. Pharmacologic
      intervention was required for persistent sleep dysfunction (n = 15, 71%) and
      headache (n = 12, 57%). Fourteen individuals (67%) were held from work at the
      time of multidisciplinary evaluation. Of those, 7 began graduated return to work
      with restrictions in place, home exercise programs, and higher-level work-focused
      cognitive rehabilitation. Conclusions and Relevance: In this preliminary report
      of a retrospective case series, persistent cognitive, vestibular, and oculomotor
      dysfunction, as well as sleep impairment and headaches, were observed among US
      government personnel in Havana, Cuba, associated with reports of directional
      audible and/or sensory phenomena of unclear origin. These individuals appeared to
      have sustained injury to widespread brain networks without an associated history
      of head trauma.

PMID- 29450486
TI  - Differentiating Acute and Subacute Vertical Strabismus Using Different Head
      Positions During the Upright-Supine Test.
AB  - Importance: Accurate clinical differentiation between skew deviation and fourth
      nerve palsy (4NP) is critical in the acute and subacute settings. Objective: To
      determine the sensitivity and specificity of the upright-supine test to detect
      vertical misalignment changes using different head positions for the diagnosis of
      acute or subacute skew deviation vs 4NP. Design, Setting, and Participants: This
      multicenter study enrolled consecutive patients from Coimbra University Hospital
      Centre, Coimbra, Portugal, and Michigan State University, Lansing, within 2
      months of presenting with vertical diplopia and diagnosed as having skew
      deviation or acquired unilateral 4NP. The study used nonmasked screening and
      diagnostic test results from June 1, 2013, to December 31, 2016. Data were
      analyzed from January 1, 2017, to June 30, 2017. Main Outcomes and Measures: A
      50% or greater change in vertical misalignment between the upright and supine
      positions, with the head centered and tilted to either side. Measurements
      included the alternate prism and cover (APC) test, the double Maddox rod test,
      the APC test change index ([measurement upright - measurement supine] /
      [measurement upright + measurement supine]), and the APC test sensitivity and
      specificity. Results: Of the 37 included patients, the mean (SD) age was 58 (14)
      years, and 26 (70%) were male. We enrolled 19 patients (51%) with skew deviation
      and 18 (49%) with 4NP. Eighteen patients with skew deviation (95%) showed
      additional ocular motor and/or neurological signs. When moving to the supine
      position, only 1 patient with skew deviation (5%) showed more than a 50% decrease
      of hypertropia with the head centered (APC test: sensitivity, 5%; specificity,
      100%). Three patients with 4NP (17%) showed more than a 50% decrease of
      hypertropia with the head tilted toward the hypertropic eye, and 10 patients with
      4NP (56%) showed more than a 50% increase of hypertropia with the head tilted
      toward the hypotropic eye. Change indexes were different between the skew
      deviation and 4NP groups for head tilt to the hypotropic eye (difference, -0.33
      prism diopters; 95% CI, -0.43 to -0.20; P < .001). Cyclotorsion worsened in the
      supine position only in patients with skew deviation (hypertropic eye:
      difference, -7.6 prism diopters; 95% CI, -13.00 to -0.75; P = .01; hypotropic
      eye: difference, 8.2 prism diopters; 95% CI, 0 to 15.75; P = .03). Conclusions
      and Relevance: The upright-supine test with the head centered is not a sensitive
      method to separate acute or subacute skew deviation from 4NP. Conversion of an
      incomitant vertical deviation in the upright position to a comitant vertical
      strabismus in the supine position in all head positions, as well as the absence
      of additional ocular motor and/or neurologic signs, may constitute a more useful
      clue.

PMID- 29450487
TI  - Systolic Blood Pressure and Outcomes in Patients With Heart Failure With
      Preserved Ejection Fraction.
AB  - Importance: Lower systolic blood pressure (SBP) levels are associated with poor
      outcomes in patients with heart failure. Less is known about this association in
      heart failure with preserved ejection fraction (HFpEF). Objective: To determine
      the associations of SBP levels with mortality and other outcomes in HFpEF.
      Design, Setting, and Participants: A propensity score-matched observational study
      of the Medicare-linked Organized Program to Initiate Lifesaving Treatment in
      Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry included 25 354
      patients who were discharged alive; 8873 (35.0%) had an ejection fraction of at
      least 50%, and of these, 3915 (44.1%) had stable SBP levels (<=20 mm Hg admission
      to discharge variation). Data were collected from 259 hospitals in 48 states
      between March 1, 2003, and December 31, 2004. Data were analyzed from March 1,
      2003, to December 31, 2008. Exposure: Discharge SBP levels less than 120 mm Hg. A
      total of 1076 of 3915 (27.5%) had SBP levels less than 120 mm Hg, of whom 901
      (83.7%) were matched by propensity scores with 901 patients with SBP levels of
      120 mm Hg or greater who were balanced on 58 baseline characteristics. Main
      Outcomes and Measures: Thirty-day, 1-year, and overall all-cause mortality and
      heart failure readmission through December 31, 2008. Results: The 1802 matched
      patients had a mean (SD) age of 79 (10) years; 1147 (63.7%) were women, and 134
      (7.4%) were African American. Thirty-day all-cause mortality occurred in 91 (10%)
      and 45 (5%) of matched patients with discharge SBP of less than 120 mm Hg vs 120
      mm Hg or greater, respectively (hazard ratio [HR], 2.07; 95% CI, 1.45-2.95; P <
      .001). Systolic blood pressure level less than 120 mm Hg was also associated with
      a higher risk of mortality at 1 year (39% vs 31%; HR, 1.36; 95% CI, 1.16-1.59; P
      < .001) and during a median follow-up of 2.1 (overall 6) years (HR, 1.17; 95% CI,
      1.05-1.30; P = .005). Systolic blood pressure level less than 120 mm Hg was
      associated with a higher risk of heart failure readmission at 30 days (HR, 1.47;
      95% CI, 1.08-2.01; P = .02) but not at 1 or 6 years. Hazard ratios for the
      combined end point of heart failure readmission or all-cause mortality associated
      with SBP level less than 120 mm at 30 days, 1 year, and overall were 1.71 (95%
      CI, 1.34-2.18; P < .001), 1.21 (95% CI, 1.07-1.38; P = .004), and 1.12 (95% CI,
      1.01-1.24; P = .03), respectively. Conclusions and Relevance: Among hospitalized
      patients with HFpEF, an SBP level less than 120 mm Hg is significantly associated
      with poor outcomes. Future studies need to prospectively evaluate optimal SBP
      treatment goals in patients with HFpEF.

PMID- 29450488
TI  - Spatial Release From Masking in Adults With Bilateral Cochlear Implants: Effects
      of Distracter Azimuth and Microphone Location.
AB  - Purpose: The primary purpose of this study was to derive spatial release from
      masking (SRM) performance-azimuth functions for bilateral cochlear implant (CI)
      users to provide a thorough description of SRM as a function of target/distracter
      spatial configuration. The secondary purpose of this study was to investigate the
      effect of the microphone location for SRM in a within-subject study design.
      Method: Speech recognition was measured in 12 adults with bilateral CIs for 11
      spatial separations ranging from -90 degrees  to +90 degrees  in 20 degrees 
      steps using an adaptive block design. Five of the 12 participants were tested
      with both the behind-the-ear microphones and a T-mic configuration to further
      investigate the effect of mic location on SRM. Results: SRM can be significantly
      affected by the hemifield origin of the distracter stimulus-particularly for
      listeners with interaural asymmetry in speech understanding. The greatest SRM was
      observed with a distracter positioned 50 degrees  away from the target. There was
      no effect of mic location on SRM for the current experimental design. Conclusion:
      Our results demonstrate that the traditional assessment of SRM with a distracter
      positioned at 90 degrees  azimuth may underestimate maximum performance for
      individuals with bilateral CIs.

PMID- 29450489
TI  - Evaluating Readmission-Need for More Clarity on Methods-Reply.

PMID- 29450490
TI  - Neurological Symptoms Among US Diplomats in Cuba.

PMID- 29450491
TI  - Potential Confounders in an Investigation of the Vision-Related Functional Burden
      of Diabetic Retinopathy-Reply.

PMID- 29450492
TI  - Do All Patients Need beta-Blockers After a Heart Attack?

PMID- 29450493
TI  - The Impact of Age, Background Noise, Semantic Ambiguity, and Hearing Loss on
      Recognition Memory for Spoken Sentences.
AB  - Purpose: The goal of this study was to determine how background noise, linguistic
      properties of spoken sentences, and listener abilities (hearing sensitivity and
      verbal working memory) affect cognitive demand during auditory sentence
      comprehension. Method: We tested 30 young adults and 30 older adults.
      Participants heard lists of sentences in quiet and in 8-talker babble at signal
      to-noise ratios of +15 dB and +5 dB, which increased acoustic challenge but left
      the speech largely intelligible. Half of the sentences contained semantically
      ambiguous words to additionally manipulate cognitive challenge. Following each
      list, participants performed a visual recognition memory task in which they
      viewed written sentences and indicated whether they remembered hearing the
      sentence previously. Results: Recognition memory (indexed by d') was poorer for
      acoustically challenging sentences, poorer for sentences containing ambiguous
      words, and differentially poorer for noisy high-ambiguity sentences. Similar
      patterns were observed for Z-transformed response time data. There were no main
      effects of age, but age interacted with both acoustic clarity and semantic
      ambiguity such that older adults' recognition memory was poorer for acoustically
      degraded high-ambiguity sentences than the young adults'. Within the older adult
      group, exploratory correlation analyses suggested that poorer hearing ability was
      associated with poorer recognition memory for sentences in noise, and better
      verbal working memory was associated with better recognition memory for sentences
      in noise. Conclusions: Our results demonstrate listeners' reliance on domain
      general cognitive processes when listening to acoustically challenging speech,
      even when speech is highly intelligible. Acoustic challenge and semantic
      ambiguity both reduce the accuracy of listeners' recognition memory for spoken
      sentences. Supplemental Materials: https://doi.org/10.23641/asha.5848059.

PMID- 29450495
TI  - Tutorial and Guidelines on Measurement of Sound Pressure Level in Voice and
      Speech.
AB  - Purpose: Sound pressure level (SPL) measurement of voice and speech is often
      considered a trivial matter, but the measured levels are often reported
      incorrectly or incompletely, making them difficult to compare among various
      studies. This article aims at explaining the fundamental principles behind these
      measurements and providing guidelines to improve their accuracy and
      reproducibility. Method: Basic information is put together from standards,
      technical, voice and speech literature, and practical experience of the authors
      and is explained for nontechnical readers. Results: Variation of SPL with
      distance, sound level meters and their accuracy, frequency and time weightings,
      and background noise topics are reviewed. Several calibration procedures for SPL
      measurements are described for stand-mounted and head-mounted microphones.
      Conclusions: SPL of voice and speech should be reported together with the mouth
      to-microphone distance so that the levels can be related to vocal power. Sound
      level measurement settings (i.e., frequency weighting and time
      weighting/averaging) should always be specified. Classified sound level meters
      should be used to assure measurement accuracy. Head-mounted microphones placed at
      the proximity of the mouth improve signal-to-noise ratio and can be taken
      advantage of for voice SPL measurements when calibrated. Background noise levels
      should be reported besides the sound levels of voice and speech.

PMID- 29450494
TI  - Comparison of the Performance of 6 Prognostic Signatures for Estrogen Receptor
      Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.
AB  - Importance: Multiple molecular signatures are available for managing estrogen
      receptor (ER)-positive breast cancer but with little direct comparative
      information to guide the patient's choice. Objective: To conduct a within-patient
      comparison of the prognostic value of 6 multigene signatures in women with early
      ER-positive breast cancer who received endocrine therapy for 5 years. Design,
      Setting, and Participants: This retrospective biomarker analysis included 774
      postmenopausal women with ER-positive ERBB2 (formerly HER2)-negative breast
      cancer. This analysis was performed as a preplanned secondary study of data from
      the Anastrozole or Tamoxifen Alone or Combined randomized clinical trial
      comparing 5-year treatment with anastrozole vs tamoxifen with 10-year follow-up
      data. The signatures included the Oncotype Dx recurrence score, PAM50-based
      Prosigna risk of recurrence (ROR), Breast Cancer Index (BCI), EndoPredict
      (EPclin), Clinical Treatment Score, and 4-marker immunohistochemical score. Data
      were collected from January 2009, through April 2015. Main Outcomes and Measures:
      The primary objective was to compare the prognostic value of these signatures in
      addition to the Clinical Treatment Score (nodal status, tumor size, grade, age,
      and endocrine treatment) for distant recurrence for 0 to 10 years and 5 to 10
      years after diagnosis. Likelihood ratio (LR) statistics were used with the chi2
      test and C indexes to assess the prognostic value of each signature. Results: In
      this study of 774 postmenopausal women with ER-positive, ERBB2-negative disease
      (mean [SD] age, 64.1 [8.1] years), 591 (mean [SD] age, 63.4 [7.9] years) had node
      negative disease. The signatures providing the most prognostic information were
      the ROR (hazard ratio [HR], 2.56; 95% CI, 1.96-3.35), followed by the BCI (HR,
      2.46; 95% CI, 1.88-3.23) and EPclin (HR, 2.14; 95% CI, 1.71-2.68). Each provided
      significantly more information than the Clinical Treatment Score (HR, 1.99; 95%
      CI, 1.58-2.50), the recurrence score (HR, 1.69; 95% CI, 1.40-2.03), and the 4
      marker immunohistochemical score (HR, 1.95; 95% CI, 1.55-2.45). Substantially
      less information was provided by all 6 molecular tests for the 183 patients with
      1 to 3 positive nodes, but the BCI (DeltaLR chi2 = 9.2) and EPclin (DeltaLR chi2
      = 7.4) provided more additional prognostic information than the other signatures.
      Conclusions and Relevance: For women with node-negative disease, the ROR, BCI,
      and EPclin were significantly more prognostic for overall and late distant
      recurrence. For women with 1 to 3 positive nodes, limited independent information
      was available from any test. These data might help oncologists and patients to
      choose the most appropriate test when considering chemotherapy use and/or
      extended endocrine therapy. Trial Registration: isrctn.com Identifier:
      ISRCTN18233230.

PMID- 29450496
TI  - Association of Metabolic Syndrome With Sudden Sensorineural Hearing Loss.
AB  - Importance: Each of the 5 diagnostic criteria or factors of metabolic syndrome
      hyperglycemia or type 2 diabetes, hypertension, obesity, elevated triglyceride
      levels, and decreased high-density lipoprotein cholesterol level-is associated
      with the pathophysiologic features of sudden sensorineural hearing loss (SSNHL).
      Little is known, however, about the association of metabolic syndrome, defined as
      the presence of at least 3 of these factors, with the prognosis of SSNHL.
      Objective: To evaluate the association of metabolic syndrome with the rate of
      recovery from SSNHL. Design, Setting, and Participants: This retrospective
      medical record review of 124 patients treated for SSNHL at a single tertiary
      university hospital was performed from June 1, 2014, through May 31, 2016.
      Medical records were reviewed for demographic and clinical characteristics and
      audiologic variables. Exposure: Sudden sensorineural hearing loss. Main Outcomes
      and Measures: Correlation among demographic and clinical characteristics,
      audiologic results, and prognosis. Results: Of the total 124 patients (52 men
      [41.9%]; 72 women [58.1%]; mean [SD] age, 56.0 [14.6] years), 70 had metabolic
      syndrome and 54 did not. Rates of type 2 diabetes (36 [51.4%] vs 6 [11.1%]; mean
      difference [MD], 40.3%; 95% CI, 24.4%-53.1%), hypertension (46 [65.7%] vs 9
      [16.7%]; MD, 49.1%; 95% CI, 32.3%-61.7%), and obesity (47 [67.1%] vs 6 [11.1%];
      MD%, 56.0; 95% CI, 40.0%-67.5%) and mean (SD) concentrations of triglycerides
      (192.9 [159.7] vs 133.4 [116.6] mg/dL; MD, 59.4 mg/dL; 95% CI, 53.0-65.9 mg/dL)
      were significantly higher and mean (SD) concentrations of high-density
      lipoprotein cholesterol (45.8 [9.4] vs 62.6 [17.7] mg/dL; MD, 16.8 mg/dL; 95% CI,
      16.1-17.4 mg/dL) were significantly lower in the group with metabolic syndrome
      than in the group without metabolic syndrome. Mean (SD) pure-tone audiometry
      thresholds were similar at baseline in the groups with and without metabolic
      syndrome (65.0 [24.2] vs 60.8 [24.2] dB; MD, 4.3 dB; 95% CI, 3.2-5.4 dB), but
      recovery rates after treatment were significantly lower in the group with
      metabolic syndrome (16 [22.9%] vs 23 [42.6%]; MD, -19.7%; 95% CI, -35.4% to 
      3.2%). No differences were found in the 5 factors among patients with metabolic
      syndrome who did and did not recover. Level of hearing loss was higher in
      patients with than without metabolic syndrome, but the difference was not
      statistically significant. Audiogram patterns also differed but not
      significantly. Hearing recovery rates were similar in patients with 3 factors of
      metabolic syndrome and those with none but differed significantly between
      patients with 4 or more factors and those without metabolic syndrome (4 [19.0%]
      vs 27 [50.0%]; MD, -31.0%; 95% CI, -48.1% to -6.4%). Conclusions and Relevance:
      The rate of recovery from SSNHL was lower among patients with metabolic syndrome
      than among those without metabolic syndrome, and prognosis was poorer in patients
      with 4 or more diagnostic factors of the metabolic syndrome.

PMID- 29450498
TI  - Clinicians Support Medical Marijuana Use in Children With Cancer, but Lack
      Knowledge.

PMID- 29450497
TI  - Detection of Glaucoma Progression in Individuals of African Descent Compared With
      Those of European Descent.
AB  - Importance: Individuals of African descent have been reported to be at higher
      risk for becoming visually impaired from glaucoma compared with individuals of
      European descent. Objective: To investigate racial differences in longitudinal
      visual field variability and their impact on time to detect visual field
      progression. Design, Setting, and Participants: This multicenter prospective
      observational cohort study included 236 eyes of 173 individuals of European
      descent and 235 eyes of 171 individuals of African descent followed up for a mean
      (SD) time of 7.5 (3.4) years. Main Outcomes and Measures: Differences in test
      retest variability and simulated time to detect progression in individuals of
      African descent and of European descent with glaucoma. Standard automated
      perimetry mean deviation values were regressed over time for each eye, and SD of
      the residuals was used as a measure of variability. Distributions of residuals
      were used in computer simulations to reconstruct "real-world" standard automated
      perimetry mean deviation trajectories under different assumptions about rate of
      change and frequency of testing. Times to detect progression were obtained for
      the simulated visual fields. Results: Among the 344 patients, the mean (SD) age
      at baseline was 60.2 (10.0) and 60.6 (9.0) years for individuals of African
      descent and of European descent, respectively; 94 (52%) and 86 (48%) of
      individuals of African descent and of European descent were women, respectively.
      The mean SD of the residuals was larger in eyes of individuals of African descent
      vs those of European descent (1.45 [0.83] dB vs 1.12 [0.48] dB; mean difference:
      0.33 dB; 95% CI of the difference, 0.21-0.46; P < .001). The eyes in individuals
      of African descent had a larger increase in variability with worsening disease (P
      < .001). When simulations were performed assuming common progression scenarios,
      there was a delay to detect progression in eyes of individuals of African descent
      compared with those of European descent. For a scenario with baseline mean
      deviation of -10 dB and rate of change of -0.5 dB/y, detection of progression in
      individuals of African descent was delayed by 3.1 (95% CI, 2.9-3.2) years, when
      considered 80% power and annual tests. Conclusions and Relevance: Patients of
      African descent with glaucoma showed increased visual field variability compared
      with those of European descent, resulting in delayed detection of progression
      that may contribute to explain higher rates of glaucoma-related visual impairment
      in individuals of African descent compared with those of European descent with
      glaucoma.

PMID- 29450499
TI  - Otorhinolaryngology and Diving-Part 2: Otorhinolaryngological Fitness for
      Compressed Gas Scuba Diving: A Review.
AB  - Importance: Self-contained underwater breathing apparatus (scuba) diving has
      become increasingly popular with millions of people diving each year.
      Otorhinolaryngologists are often consulted either by patients or diving
      physicians regarding fitness to dive, and at present, the guidelines do not
      provide comprehensive information regarding the evaluation of this patient
      cohort. The aim of this review is to provide a comprehensive overview of existing
      otorhinolaryngological guidelines for fitness to dive recreationally.
      Observations: There is a paucity of guidelines for assessing
      otorhinolaryngological fitness to dive in the recreational diver. Comprehensive
      guidelines exist from US, European, and UK regulatory bodies regarding fitness
      for commercial diving; however, not all of these can be directly extrapolated to
      the recreational diver. There are also a variety of conditions that are not
      covered either by the existing fitness for recreational diving guidelines or the
      commercial regulatory bodies. Conclusions and Relevance: With the paucity of
      recreational fitness to dive guidelines we must draw on information from the
      commercial diving regulatory bodies. We have provided our own recommendations on
      the conditions that are not covered by either of the above, to provide
      otorhinolaryngologists with the information they require to assess fitness for
      recreational diving.

PMID- 29450500
TI  - Sixty Beats per Minute.

PMID- 29450501
TI  - Temporal estimation in prediction motion tasks is biased by a moving destination.
AB  - An ability to predict the time-to-contact (TTC) of moving objects that become
      momentarily hidden is advantageous in everyday life and could be particularly so
      in fast-ball sports. Prediction motion (PM) experiments have sought to test this
      ability using tasks where a disappearing target moves toward a stationary
      destination. Here, we developed two novel versions of the PM task in which the
      destination either moved away from (Chase) or toward (Attract) the moving target.
      The target and destination moved with different speeds such that collision
      occurred 750, 1,000 or 1,250 ms after target occlusion. To determine if domain
      specific experience conveys an advantage in PM tasks, we compared the performance
      of different sporting groups ranging from internationally competing athletes to
      non-sporting controls. There was no difference in performance between sporting
      groups and non-sporting controls but there were significant and independent
      effects on response error by target speed, destination speed, and occlusion
      period. We simulated these findings using a revised version of the linear TTC
      model of response timing for PM tasks (Yakimoff, Bocheva, & Mitrania, 1987;
      Yakimoff, Mateeff, Ehrenstein, & Hohnsbein, 1993) in which retinal input from the
      moving destination biases the internal representation of the occluded target.
      This revision closely reproduced the observed patterns of response error and thus
      describes a means by which the brain might estimate TTC when the target and
      destination are in motion.

PMID- 29450503
TI  - The Mechanical Contribution of Vimentin to Cellular Stress Generation.
AB  - Contractile stress generation by adherent cells is largely determined by the
      interplay of forces within their cytoskeleton. It is known that actin stress
      fibers, connected to focal adhesions, provide contractile stress generation,
      while microtubules and intermediate filaments provide cells compressive
      stiffness. Recent studies have shown the importance of the interplay between the
      stress fibers and the intermediate filament vimentin. Therefore, the effect of
      the interplay between the stress fibers and vimentin on stress generation was
      quantified in this study. We hypothesized that net stress generation comprises
      the stress fiber contraction combined with the vimentin resistance. We expected
      an increased net stress in vimentin knockout (VimKO) mouse embryonic fibroblasts
      (MEFs) compared to their wild-type (vimentin wild-type (VimWT)) counterparts, due
      to the decreased resistance against stress fiber contractility. To test this, the
      net stress generation by VimKO and VimWT MEFs was determined using the thin film
      method combined with sample-specific finite element modeling. Additionally, focal
      adhesion and stress fiber organization were examined via immunofluorescent
      staining. Net stress generation of VimKO MEFs was three-fold higher compared to
      VimWT MEFs. No differences in focal adhesion size or stress fiber organization
      and orientation were found between the two cell types. This suggests that the
      increased net stress generation in VimKO MEFs was caused by the absence of the
      resistance that vimentin provides against stress fiber contraction. Taken
      together, these data suggest that vimentin resists the stress fiber
      contractility, as hypothesized, thus indicating the importance of vimentin in
      regulating cellular stress generation by adherent cells.

PMID- 29450502
TI  - Poor Speech Perception Is Not a Core Deficit of Childhood Apraxia of Speech:
      Preliminary Findings.
AB  - Purpose: Childhood apraxia of speech (CAS) is hypothesized to arise from deficits
      in speech motor planning and programming, but the influence of abnormal speech
      perception in CAS on these processes is debated. This study examined speech
      perception abilities among children with CAS with and without language impairment
      compared to those with language impairment, speech delay, and typically
      developing peers. Method: Speech perception was measured by discrimination of
      synthesized speech syllable continua that varied in frequency (/dalpha/
      /galpha/). Groups were classified by performance on speech and language
      assessments and compared on syllable discrimination thresholds. Within-group
      variability was also evaluated. Results: Children with CAS without language
      impairment did not significantly differ in syllable discrimination compared to
      typically developing peers. In contrast, those with CAS and language impairment
      showed significantly poorer syllable discrimination abilities compared to
      children with CAS only and typically developing peers. Children with speech delay
      and language impairment also showed significantly poorer discrimination
      abilities, with appreciable within-group variability. Conclusions: These findings
      suggest that speech perception deficits are not a core feature of CAS but rather
      occur with co-occurring language impairment in a subset of children with CAS.
      This study establishes the significance of accounting for language ability in
      children with CAS. Supplemental Materials: https://doi.org/10.23641/asha.5848056.

PMID- 29450505
TI  - In Shadow and Light-Images of Transformation Through Breast Cancer.

PMID- 29450504
TI  - Association of Adenotonsillectomy With Blood Pressure Among Hypertensive and
      Nonhypertensive Children With Obstructive Sleep Apnea.
AB  - Importance: Hypertension in childhood may continue into adulthood and lead to
      adverse cardiovascular outcomes. Evidence suggests that adenotonsillectomy for
      childhood obstructive sleep apnea (OSA) may be associated with blood pressure
      (BP) improvement. However, how adenotonsillectomy is associated with BP in
      hypertensive and nonhypertensive children with OSA remains unclear. Objective: To
      investigate disparities in BP changes after adenotonsillectomy in hypertensive
      and nonhypertensive children with OSA. Design, Setting, and Participants: From
      January 1, 2010, to April 30, 2016, children (aged <18 years) with symptoms of
      OSA treated at National Taiwan University Hospital were enrolled in this
      retrospective case series study. Interventions: Children underwent
      polysomnography for diagnosis of OSA (apnea-hypopnea index >1). All children with
      OSA underwent adenotonsillectomy. Main Outcomes and Measures: Preoperative and
      postoperative overnight polysomnographic data were obtained. Office BP was
      measured in a sleep center before (nocturnal BP) and after (morning)
      polysomnography. Results: A total of 240 nonobese children (mean [SD] age, 7.3
      [3.0] years; 160 [66.7%] male and 80 [33.3%] female) with OSA were recruited.
      Postoperatively, the apnea-hypopnea index decreased significantly from 12.1 to
      1.7 events per hour (95% CI of difference, -12.3 to -8.4 events per hour). The
      whole cohort had a significant decrease in nocturnal diastolic BP (66.9 to 64.5
      mm Hg; 95% CI of difference, -4.1 to -0.7 mm Hg) and morning diastolic BP (66.9
      to 64.4 mm Hg; 95% CI of difference, -4.2 to -0.8 mm Hg). The number (percentage)
      of patients with diastolic BP in the greater than 95th percentile decreased
      significantly nocturnally (48 [20.0%] to 33 [13.8%]; 95% CI of difference, -12.1%
      to -0.4%) and in the morning (52 [21.7%] to 34 [14.2%]; 95% CI of difference, 
      13.6% to -1.4%). Postoperatively, hypertensive children had a significant
      decrease in all BP measures, including mean (SD) nocturnal and morning systolic
      BP (nocturnal: 107.5 [8.6] mm Hg; morning: 106.0 [9.4] mm Hg), systolic BP index
      (nocturnal: -4.3 [8.6]; morning: -5.7 [8.5]), diastolic BP (nocturnal: 65.1
      [11.5] mm Hg; morning: 64.4 [10.1] mm Hg), and diastolic BP index (nocturnal: 
      10.7 [17.3]; morning: -11.6 [15.7]), whereas the nonhypertensive group had a
      slight increase in nocturnal systolic BP (103.8 to 105.9 mm Hg; 95% CI of
      difference, 0.4-3.9 mm Hg). A generalized estimating equation model for subgroup
      comparisons revealed that children with hypertension, compared with those
      without, had greater improvement in all BP measures. Conclusions and Relevance:
      Hypertensive children with OSA had a significant improvement in BP after
      adenotonsillectomy. Hypertensive children with OSA should be screened and treated
      by adenotonsillectomy because proper treatment not only eases OSA symptoms but
      also potentially prevents future cardiovascular and end-organ disease.

PMID- 29450506
TI  - Urine Test for Tuberculosis in Development.

PMID- 29450507
TI  - Hemophilia Gene Therapies Show Promise.

PMID- 29450508
TI  - Error in Author Degree and Surname.

PMID- 29450509
TI  - Screening for Ovarian Cancer in Asymptomatic Women.

PMID- 29450510
TI  - Utility of a Clinical Prediction Rule to Exclude Pulmonary Embolism Among Low
      Risk Emergency Department Patients: Reason to PERC Up.

PMID- 29450511
TI  - Improving Evidence for Implementation of Guideline-Based Care in Low- and Middle
      Income Countries.

PMID- 29450512
TI  - The Stepped-Wedge Clinical Trial: Evaluation by Rolling Deployment.

PMID- 29450514
TI  - Our Forefathers' Knowledge.

PMID- 29450515
TI  - Gender and Byline Placement of Co-first Authors in Clinical and Basic Science
      Journals With High Impact Factors.

PMID- 29450516
TI  - Paid Family and Childbearing Leave Policies at Top US Medical Schools.

PMID- 29450517
TI  - Costs of Quality Measurement.

PMID- 29450518
TI  - Early Resuscitation for Adults With Sepsis in a Low-Income Country.

PMID- 29450519
TI  - Absolute vs Additive Net Reclassification Index.

PMID- 29450520
TI  - Costs of Quality Measurement-Reply.

PMID- 29450521
TI  - Early Resuscitation for Adults With Sepsis in a Low-income Country-Reply.

PMID- 29450522
TI  - Absolute vs Additive Net Reclassification Index-Reply.

PMID- 29450523
TI  - Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic
      Events Among Low-Risk Emergency Department Patients: The PROPER Randomized
      Clinical Trial.
AB  - Importance: The safety of the pulmonary embolism rule-out criteria (PERC), an 8
      item block of clinical criteria aimed at ruling out pulmonary embolism (PE), has
      not been assessed in a randomized clinical trial. Objective: To prospectively
      validate the safety of a PERC-based strategy to rule out PE. Design, Setting, and
      Patients: A crossover cluster-randomized clinical noninferiority trial in 14
      emergency departments in France. Patients with a low gestalt clinical probability
      of PE were included from August 2015 to September 2016, and followed up until
      December 2016. Interventions: Each center was randomized for the sequence of
      intervention periods. In the PERC period, the diagnosis of PE was excluded with
      no further testing if all 8 items of the PERC rule were negative. Main Outcomes
      and Measures: The primary end point was the occurrence of a thromboembolic event
      during the 3-month follow-up period that was not initially diagnosed. The
      noninferiority margin was set at 1.5%. Secondary end points included the rate of
      computed tomographic pulmonary angiography (CTPA), median length of stay in the
      emergency department, and rate of hospital admission. Results: Among 1916
      patients who were cluster-randomized (mean age 44 years, 980 [51%] women), 962
      were assigned to the PERC group and 954 were assigned to the control group. A
      total of 1749 patients completed the trial. A PE was diagnosed at initial
      presentation in 26 patients in the control group (2.7%) vs 14 (1.5%) in the PERC
      group (difference, 1.3% [95% CI, -0.1% to 2.7%]; P = .052). One PE (0.1%) was
      diagnosed during follow-up in the PERC group vs none in the control group
      (difference, 0.1% [95% CI, -infinity to 0.8%]). The proportion of patients
      undergoing CTPA in the PERC group vs control group was 13% vs 23% (difference, 
      10% [95% CI, -13% to -6%]; P < .001). In the PERC group, rates were significantly
      reduced for the median length of emergency department stay (mean reduction, 36
      minutes [95% CI, 4 to 68]) and hospital admission (difference, 3.3% [95% CI, 0.1%
      to 6.6%]). Conclusions and Relevance: Among very low-risk patients with suspected
      PE, randomization to a PERC strategy vs conventional strategy did not result in
      an inferior rate of thromboembolic events over 3 months. These findings support
      the safety of PERC for very low-risk patients presenting to the emergency
      department. Trial Registration: clinicaltrials.gov Identifier: NCT02375919.

PMID- 29450524
TI  - Effect of a Quality Improvement Intervention on Clinical Outcomes in Patients in
      India With Acute Myocardial Infarction: The ACS QUIK Randomized Clinical Trial.
AB  - Importance: Wide heterogeneity exists in acute myocardial infarction treatment
      and outcomes in India. Objective: To evaluate the effect of a locally adapted
      quality improvement tool kit on clinical outcomes and process measures in Kerala,
      a southern Indian state. Design, Setting, and Participants: Cluster randomized,
      stepped-wedge clinical trial conducted between November 10, 2014, and November 9,
      2016, in 63 hospitals in Kerala, India, with a last date of follow-up of December
      31, 2016. During 5 predefined steps over the study period, hospitals were
      randomly selected to move in a 1-way crossover from the control group to the
      intervention group. Consecutively presenting patients with acute myocardial
      infarction were offered participation. Interventions: Hospitals provided either
      usual care (control group; n = 10 066 participants [step 0: n = 2915; step 1: n =
      2649; step 2: n = 2251; step 3: n = 1422; step 4; n = 829; step 5: n = 0]) or
      care using a quality improvement tool kit (intervention group; n = 11 308
      participants [step 0: n = 0; step 1: n = 662; step 2: n = 1265; step 3: n = 2432;
      step 4: n = 3214; step 5: n = 3735]) that consisted of audit and feedback,
      checklists, patient education materials, and linkage to emergency cardiovascular
      care and quality improvement training. Main Outcomes and Measures: The primary
      outcome was the composite of all-cause death, reinfarction, stroke, or major
      bleeding using standardized definitions at 30 days. Secondary outcomes included
      the primary outcome's individual components, 30-day cardiovascular death,
      medication use, and tobacco cessation counseling. Mixed-effects logistic
      regression models were used to account for clustering and temporal trends.
      Results: Among 21 374 eligible randomized participants (mean age, 60.6 [SD, 12.0]
      years; n = 16 183 men [76%] ; n = 13 689 [64%] with ST-segment elevation
      myocardial infarction), 21 079 (99%) completed the trial. The primary composite
      outcome was observed in 5.3% of the intervention participants and 6.4% of the
      control participants. The observed difference in 30-day major adverse
      cardiovascular event rates between the groups was not statistically significant
      after adjustment (adjusted risk difference, -0.09% [95% CI, -1.32% to 1.14%];
      adjusted odds ratio, 0.98 [95% CI, 0.80-1.21]). The intervention group had a
      higher rate of medication use including reperfusion but no effect on tobacco
      cessation counseling. There were no unexpected adverse events reported.
      Conclusions and Relevance: Among patients with acute myocardial infarction in
      Kerala, India, use of a quality improvement intervention compared with usual care
      did not decrease a composite of 30-day major adverse cardiovascular events.
      Further research is needed to understand the lack of efficacy. Trial
      Registration: clinicaltrials.gov Identifier: NCT02256657.

PMID- 29450526
TI  - Screening for Ovarian Cancer.

PMID- 29450528
TI  - I Solemnly Share.

PMID- 29450525
TI  - Association of the Affordable Care Act Dependent Coverage Provision With Prenatal
      Care Use and Birth Outcomes.
AB  - Importance: The effect of the Affordable Care Act (ACA) dependent coverage
      provision on pregnancy-related health care and health outcomes is unknown.
      Objective: To determine whether the dependent coverage provision was associated
      with changes in payment for birth, prenatal care, and birth outcomes. Design,
      Setting, and Participants: Retrospective cohort study, using a differences-in
      differences analysis of individual-level birth certificate data comparing live
      births among US women aged 24 to 25 years (exposure group) and women aged 27 to
      28 years (control group) before (2009) and after (2011-2013) enactment of the
      dependent coverage provision. Results were stratified by marital status. Main
      Exposures: The dependent coverage provision of the ACA, which allowed young
      adults to stay on their parent's health insurance until age 26 years. Main
      Outcomes and Measures: Primary outcomes were payment source for birth, early
      prenatal care (first visit in first trimester), and adequate prenatal care (a
      first trimester visit and 80% of expected visits). Secondary outcomes were
      cesarean delivery, premature birth, low birth weight, and infant neonatal
      intensive care unit (NICU) admission. Results: The study population included 1
      379 005 births among women aged 24-25 years (exposure group; 299 024 in 2009; 1
      079 981 in 2011-2013), and 1 551 192 births among women aged 27-28 years (control
      group; 325 564 in 2009; 1 225 628 in 2011-2013). From 2011-2013, compared with
      2009, private insurance payment for births increased in the exposure group (36.9%
      to 35.9% [difference, -1.0%]) compared with the control group (52.4% to 51.1%
      [difference, -1.3%]), adjusted difference-in-differences, 1.9 percentage points
      (95% CI, 1.6 to 2.1). Medicaid payment decreased in the exposure group (51.6% to
      53.6% [difference, 2.0%]) compared with the control group (37.4% to 39.4%
      [difference, 1.9%]), adjusted difference-in-differences, -1.4 percentage points
      (95% CI, -1.7 to -1.2). Self-payment for births decreased in the exposure group
      (5.2% to 4.3% [difference, -0.9%]) compared with the control group (4.9% to 4.3%
      [difference, -0.5%]), adjusted difference-in-differences, -0.3 percentage points
      (95% CI, -0.4 to -0.1). Early prenatal care increased from 70% to 71.6%
      (difference, 1.6%) in the exposure group and from 75.7% to 76.8% (difference,
      0.6%) in the control group (adjusted difference-in-differences, 0.6 percentage
      points [95% CI, 0.3 to 0.8]). Adequate prenatal care increased from 73.5% to
      74.8% (difference, 1.3%) in the exposure group and from 77.5% to 78.8%
      (difference, 1.3%) in the control group (adjusted difference-in-differences, 0.4
      percentage points [95% CI, 0.2 to 0.6]). Preterm birth decreased from 9.4% to
      9.1% in the exposure group (difference, -0.3%) and from 9.1% to 8.9% in the
      control group (difference, -0.2%) (adjusted difference-in-differences, -0.2
      percentage points (95% CI, -0.3 to -0.03). Overall, there were no significant
      changes in low birth weight, NICU admission, or cesarean delivery. In stratified
      analyses, changes in payment for birth, prenatal care, and preterm birth were
      concentrated among unmarried women. Conclusions and Relevance: In this study of
      nearly 3 million births among women aged 24 to 25 years vs those aged 27 to 28
      years, the Affordable Care Act dependent coverage provision was associated with
      increased private insurance payment for birth, increased use of prenatal care,
      and modest reduction in preterm births, but was not associated with changes in
      cesarean delivery rates, low birth weight, or NICU admission.

PMID- 29450530
TI  - Screening for Ovarian Cancer: Updated Evidence Report and Systematic Review for
      the US Preventive Services Task Force.
AB  - Importance: Ovarian cancer is relatively rare but the fifth-leading cause of
      cancer mortality among United States women. Objective: To systematically review
      evidence on benefits and harms of ovarian cancer screening among average-risk
      women to inform the United States Preventive Services Task Force. Data Sources:
      MEDLINE, PubMed, Cochrane Collaboration Registry of Controlled Trials; studies
      published in English from January 1, 2003, through January 31, 2017; ongoing
      surveillance in targeted publications through November 22, 2017. Study Selection:
      Randomized clinical trials of ovarian cancer screening in average-risk women that
      reported mortality or quality-of-life outcomes. Interventions included
      transvaginal ultrasound, cancer antigen 125 (CA-125) testing, or their
      combination. Comparators were usual care or no screening. Data Extraction and
      Synthesis: Independent critical appraisal and data abstraction by 2 reviewers.
      Meta-analytic pooling of results was not conducted because of the small number of
      studies and heterogeneity of interventions. Main Outcomes and Measures: Ovarian
      cancer mortality, false-positive screening results and surgery, surgical
      complications, and psychological effects of screening. Results: Four trials (N =
      293 587) were included; of these, 3 (n = 293 038) assessed ovarian cancer
      mortality, and 1 (n = 549) reported only on psychological outcomes. Evaluated
      screening interventions included transvaginal ultrasound alone, transvaginal
      ultrasound plus CA-125 testing, and CA-125 testing alone. Test positivity for CA
      125 was defined by a fixed serum level cutpoint or by a proprietary risk
      algorithm based on CA-125 level, change in CA-125 level over time, and age (risk
      of ovarian cancer algorithm [ROCA]). No trial found a significant difference in
      ovarian cancer mortality with screening. In the 2 large screening trials (PLCO
      and UKCTOCS, n = 271 103), there was not a statistically significant difference
      in complete intention-to-screen analyses of ovarian, fallopian, and peritoneal
      cancer cases associated with screening (PLCO: rate ratio, 1.18 [95% CI, 0.82
      1.71]; UKCTOCS: hazard ratio [HR], 0.91 [95% CI, 0.76-1.09] for transvaginal
      ultrasound and HR, 0.89 [95% CI, 0.74-1.08] for CA-125 ROCA). Within these 2
      trials, screening led to surgery for suspected ovarian cancer in 1% of women
      without cancer for CA-125 ROCA and in 3% for transvaginal ultrasound with or
      without CA-125 screening, with major complications occurring among 3% to 15% of
      surgery. Evidence on psychological harms was limited but nonsignificant except in
      the case of repeat follow-up scans and tests, which increased the risk of
      psychological morbidity in a subsample of UKCTOCS participants based on the
      General Health Questionnaire 12 (score >=4) (odds ratio, 1.28 [95% CI, 1.18
      1.39]). Conclusions and Relevance: In randomized trials conducted among average
      risk, asymptomatic women, ovarian cancer mortality did not significantly differ
      between screened women and those with no screening or in usual care. Screening
      harms included surgery (with major surgical complications) in women found to not
      have cancer. Further research is needed to identify effective approaches for
      reducing ovarian cancer incidence and mortality.

PMID- 29450532
TI  - State Restrictions of e-Cigarette Use Has Slowed.

PMID- 29450533
TI  - Obesity Tied to Income, Education, But Not in All Populations.

PMID- 29450531
TI  - Screening for Ovarian Cancer: US Preventive Services Task Force Recommendation
      Statement.
AB  - Importance: With approximately 14 000 deaths per year, ovarian cancer is the
      fifth most common cause of cancer death among US women and the leading cause of
      death from gynecologic cancer. More than 95% of ovarian cancer deaths occur among
      women 45 years and older. Objective: To update the 2012 US Preventive Services
      Task Force (USPSTF) recommendation on screening for ovarian cancer. Evidence
      Review: The USPSTF reviewed the evidence on the benefits and harms of screening
      for ovarian cancer in asymptomatic women not known to be at high risk for ovarian
      cancer (ie, high risk includes women with certain hereditary cancer syndromes
      that increase their risk for ovarian cancer). Outcomes of interest included
      ovarian cancer mortality, quality of life, false-positive rate, surgery and
      surgical complication rates, and psychological effects of screening. Findings:
      The USPSTF found adequate evidence that screening for ovarian cancer does not
      reduce ovarian cancer mortality. The USPSTF found adequate evidence that the
      harms from screening for ovarian cancer are at least moderate and may be
      substantial in some cases, and include unnecessary surgery for women who do not
      have cancer. Given the lack of mortality benefit of screening, and the moderate
      to substantial harms that could result from false-positive screening test results
      and subsequent surgery, the USPSTF concludes with moderate certainty that the
      harms of screening for ovarian cancer outweigh the benefit, and the net balance
      of the benefit and harms of screening is negative. Conclusions and
      Recommendation: The USPSTF recommends against screening for ovarian cancer in
      asymptomatic women. (D recommendation) This recommendation applies to
      asymptomatic women who are not known to have a high-risk hereditary cancer
      syndrome.

PMID- 29450534
TI  - Reading Behind the Lines: The Factors Affecting the Text Reception Threshold in
      Hearing Aid Users.
AB  - Purpose: The visual Text Reception Threshold (TRT) test (Zekveld et al., 2007)
      has been designed to assess modality-general factors relevant for speech
      perception in noise. In the last decade, the test has been adopted in audiology
      labs worldwide. The 1st aim of this study was to examine which factors best
      predict interindividual differences in the TRT. Second, we aimed to assess the
      relationships between the TRT and the speech reception thresholds (SRTs)
      estimated in various conditions. Method: First, we reviewed studies reporting
      relationships between the TRT and the auditory and/or cognitive factors and
      formulated specific hypotheses regarding the TRT predictors. These hypotheses
      were tested using a prediction model applied to a rich data set of 180 hearing
      aid users. In separate association models, we tested the relationships between
      the TRT and the various SRTs and subjective hearing difficulties, while taking
      into account potential confounding variables. Results: The results of the
      prediction model indicate that the TRT is predicted by the ability to fill in
      missing words in incomplete sentences, by lexical access speed, and by working
      memory capacity. Furthermore, in line with previous studies, a moderate
      association between higher age, poorer pure-tone hearing acuity, and poorer TRTs
      was observed. Better TRTs were associated with better SRTs for the correct
      perception of 50% of Hagerman matrix sentences in a 4-talker babble, as well as
      with better subjective ratings of speech perception. Age and pure-tone hearing
      thresholds significantly confounded these associations. The associations of the
      TRT with SRTs estimated in other conditions and with subjective qualities of
      hearing were not statistically significant when adjusting for age and pure-tone
      average. Conclusions: We conclude that the abilities tapped into by the TRT test
      include processes relevant for speeded lexical decision making when completing
      partly masked sentences and that these processes require working memory capacity.
      Furthermore, the TRT is associated with the SRT of hearing aid users as estimated
      in a challenging condition that includes informational masking and with
      experienced difficulties with speech perception in daily-life conditions. The
      current results underline the value of using the TRT test in studies involving
      speech perception and aid in the interpretation of findings acquired using the
      test.

PMID- 29450535
TI  - A Spatiotemporal Requirement for Prickle 1-Mediated PCP Signaling in Eyelid
      Morphogenesis and Homeostasis.
AB  - Purpose: Tissue closure/fusion is a fundamental process during organogenesis,
      driven in part by the Wnt/planar cell polarity (Wnt/PCP) pathway. This study
      explored the spatial and temporal aspects of PCP signaling in eyelid development
      through analysis of mice lacking Prickle 1, a core PCP component, and the
      Prickle1-dependent signaling networks underlying eyelid development. Methods:
      Wild type and Prickle 1 compound mutant mice with a hypomorphic and a null allele
      were bred and used to study eyelid morphogenesis. The time course of embryonic
      eyelid fusion and postnatal reopening was examined by light microscopy of tissue
      sections and scanning electron microscopy. Immunohistochemistry was conducted to
      monitor cell proliferation, death, and molecular identities through pre- and
      postnatal eyelid development. Results: Prickle 1 mutant embryos exhibited a
      profound delay in eyelid closure at embryonic ages, but manifested precocious
      eyelid reopening postnatally, with ensuing cornea malformation. Mutant embryonic
      showed downregulation of phosphorylated c-Jun, and upregulation of increased beta
      catenin in separate cell populations of the eyelid front area. Increased cell
      death and decreased mesenchymal infiltration was observed in postnatal mutant
      eyelid prior to eyelid reopening. While broadly expressed in many tissues,
      Prickle 1 was spatially restricted to the eyelid front at E15.5, a location where
      c-Jun and beta-catenin expression was altered in Prickle 1 mutants. Conclusions:
      The study demonstrates a spatiotemporal requirement for Prickle 1-mediated PCP
      signaling during eyelid morphogenesis and homeostasis. The study links Prickle 1
      mediated PCP signaling to existing networks, and provides a useful animal model
      for studying congenital ocular surface diseases.

PMID- 29450536
TI  - Administration of Nitric Oxide Through a Novel Copper-Chitosan Delivery System in
      Human Corneal and Limbal Epithelial Cell Injury.
AB  - Purpose: Nitric oxide (NO) has gained attention for its role in facilitating
      wound healing by promoting cell migration, while being cytoprotective in a
      variety of cell types. We determined the efficacy of NO, administered using a
      novel application of copper-chitosan treatments (Cu-Ch), in facilitating corneal
      epithelial wound healing using an in vitro model of corneal epithelial and limbal
      epithelial cell injury. Methods: Human corneal epithelial (HCE) and human limbal
      epithelial (HLE) cells were monitored under no-scratch (CON), untreated scratch
      (CS), scratch + plain chitosan composite (0%), scratch + 1% copper solution Cu-Ch
      (1%), and scratch + 2% copper solution Cu-Ch (2%) conditions. Cell migration,
      cytotoxicity, apoptosis, and total nitrate/nitrite concentrations were measured
      at 24, 48, and 72 hours after injury and treatment. iNOS expression in HLE cells
      also was determined using Western blot. Results: Wound closure significantly
      increased in HCE cells treated with Cu-Ch (1% and 2%) after 72 hours, while HLE
      cells showed a significant decrease in closure with Cu-Ch (1% and 2%) treatment
      compared to CS. Cytotoxic fragments decreased significantly with 1% and 2% Cu-Ch
      treatments in HCE cells. Nitrate/nitrite levels in HLE cells showed a significant
      increase with 2% Cu-Ch treatment compared to CS. This increase is complemented
      with an upregulation of iNOS. Conclusions: Overall, HCE wound healing was
      accelerated with administration of Cu-Ch treatment. Differences between HCE and
      HLE responses may be due to intrinsic differences in NO metabolism, as evidenced
      by differences in NO production, potentially caused by differences in iNOS
      expression with treatment.

PMID- 29450537
TI  - Enhanced Expression of NLRP3 Inflammasome-Related Inflammation in Diabetic
      Retinopathy.
AB  - Purpose: The aim of this study was to determine the association between
      nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) family,
      pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation and disease
      severity in diabetic retinopathy (DR). Methods: Blood samples were collected from
      64 patients with diabetes (DR, 43; without DR, 21) and 25 healthy controls. The
      protein and mRNA expression levels of NLRP3 inflammasomes in peripheral blood
      mononuclear cells were determined using western blotting and quantitative real
      time reverse transcription-PCR. A total of 82 vitreous samples were obtained from
      patients with DR (n = 60) and nondiabetic controls (n = 22). All patients were
      candidates for vitrectomy. Interleukin (IL)-1beta and IL-18 in the peripheral
      blood mononuclear cell culture medium and vitreous fluid were detected by enzyme
      linked immunosorbent assay (ELISA). Immunofluorescence staining for apoptosis
      associated speck-like protein with a caspase recruitment domain (ASC) and NLRP3
      was performed in fibrovascular membranes from 21 proliferative DR patients and 22
      controls with idiopathic epiretinal membranes. Results: We observed increased
      gene and protein expression of NLRP3, ASC, and caspase-1 in peripheral blood
      mononuclear cells of adults with DR compared with that in normal controls.
      Furthermore, the elevated expressions of NLRP3 and ASC were observed in the
      fibrovascular membranes from 21 adults with proliferative DR when compared with
      the 22 controls. IL-1beta and IL-18 in the peripheral blood mononuclear cells and
      vitreous fluid were elevated in the DR patients when compared with controls.
      Conclusions: These outcomes suggested that NLRP3 inflammasomes are upregulated in
      adults with DR and may play a key role in the pathogenesis and progression of DR.

PMID- 29450539
TI  - Retinothalamic White Matter Abnormalities in Amblyopia.
AB  - Purpose: Amblyopia is associated with a broad array of perceptual and neural
      abnormalities in the visual system, particularly in untreated or unsuccessfully
      treated populations. Traditionally, it has been believed that the neural
      abnormalities are confined to the visual cortex and subcortex (e.g., lateral
      geniculate nucleus). Here, we investigate the presence of neuroanatomical
      abnormalities earlier in the visual stream, in the optic nerves and tracts, of
      participants with two predominant forms of amblyopia. Methods: We used diffusion
      magnetic resonance imaging and probabilistic tractography to compare the
      microstructural properties of five white matter visual pathways between 15
      participants with amblyopia (eight anisometropic, five strabismic, and two
      exhibiting both etiologies), and 13 age-matched controls. Results: Participants
      with amblyopia exhibited significantly smaller mean fractional anisotropy in the
      optic nerve and optic tract (0.26 and 0.31 vs. 0.31 and 0.36 in controls,
      respectively). We also found greater mean diffusivity in the optic radiation
      compared to controls (0.72 MUm2/s vs. 0.68 MUm2/s, respectively). Comparing
      etiologies, the abnormalities in the precortical pathways tended to be more
      severe in participants with anisometropic compared to strabismic amblyopia, and
      anisometropic participants' optic nerves, optic tracts, and optic radiations
      significantly differed from control participants' (all, P < 0.05). Conclusions:
      The results indicate that amblyopia may be associated with microstructural
      abnormalities in neural networks as early as the retina, and these abnormalities
      may differ between amblyopic etiologies.

PMID- 29450538
TI  - Clinical Age-Specific Seasonal Conjunctivitis Patterns and Their Online Detection
      in Twitter, Blog, Forum, and Comment Social Media Posts.
AB  - Purpose: We sought to determine whether big data from social media might reveal
      seasonal trends of conjunctivitis, most forms of which are nonreportable.
      Methods: Social media posts (from Twitter, and from online forums and blogs) were
      classified by age and by conjunctivitis type (allergic or infectious) using
      Boolean and machine learning methods. Based on spline smoothing, we estimated the
      circular mean occurrence time (a measure of central tendency for occurrence) and
      the circular variance (a measure of uniformity of occurrence throughout the year,
      providing an index of seasonality). Clinical records from a large tertiary care
      provider were analyzed in a similar way for comparison. Results: Social media
      posts machine-coded as being related to infectious conjunctivitis showed similar
      times of occurrence and degree of seasonality to clinical infectious cases, and
      likewise for machine-coded allergic conjunctivitis posts compared to clinical
      allergic cases. Allergic conjunctivitis showed a distinctively different seasonal
      pattern than infectious conjunctivitis, with a mean occurrence time later in the
      spring. Infectious conjunctivitis for children showed markedly greater
      seasonality than for adults, though the occurrence times were similar; no such
      difference for allergic conjunctivitis was seen. Conclusions: Social media posts
      broadly track the seasonal occurrence of allergic and infectious conjunctivitis,
      and may be a useful supplement for epidemiologic monitoring.

PMID- 29450540
TI  - Endocan Blockade Suppresses Experimental Ocular Neovascularization in Mice.
AB  - Purpose: Ocular neovascularization (NV) is a pathologic process characterized by
      the proliferation and infiltration of various types of cells such as RPE, glial,
      and endothelial cells, which interact with proangiogenic factors and inflammatory
      cytokines. Endocan is known to be enriched in retinal endothelial tip cells under
      hypoxia, but the effect of endocan on ocular NV progression is largely unknown.
      In this study, we investigated the role of endocan in the ocular NV pathologic
      process and the possible mechanisms involved. Methods: In the eyes of mice with
      oxygen-induced retinopathy (OIR); choroidal NV (CNV); and rhodopsin promoter
      (rho)/VEGF transgenic mice, endocan expression was assessed by quantitative real
      time PCR (RT-PCR) and Western blot. In vivo, a specific functional antibody was
      used to neutralize endocan and ocular NV levels were evaluated by RT-PCR, Western
      blot and immunostaining of flat-mounts. In vitro, the effect of endocan on human
      retinal microvascular endothelial cell (HREC) tube formation was observed using a
      routine method. Results: Endocan was significantly elevated in these three
      experimental mice models. Endocan blockade with the neutralizer intravitreal
      injection not only suppressed the area of retinal, choroidal and subretinal NV,
      but also resulted in a decrease in several angiogenesis-associated molecules.
      Recombinant endocan protein (rhEndocan) was found to induce tube formation on
      HRECs directly. Conclusions: The current data suggest that endocan is a potential
      therapeutic or an additional target for retinal and subretinal NV diseases.

PMID- 29450541
TI  - Induction of Ocular Complement Activation by Inflammatory Stimuli and Intraocular
      Inhibition of Complement Factor D in Animal Models.
AB  - Purpose: Genome-wide association studies suggest a role for the complement system
      in age-related macular degeneration (AMD). We characterized ocular complement
      activation and evaluated a complement factor D (FD) neutralizing antibody.
      Methods: Mice were treated with toll-like receptor (TLR) ligands, intravitreal
      injection (IVT), or corneal debridement. Levels of complement proteins and mRNA
      were measured. A FD neutralizing antibody was administered IVT into eyes of
      rabbits that were challenged with LPS (lipopolysaccharide) administered
      intravenously. Results: Levels of C3 and factor B (FB) mRNA and protein in the
      eye were increased following intraperitoneal injection of TLR4 ligand LPS.
      Increased levels of C3 and FB breakdown products were observed in both eye
      tissues and plasma. Complement activation products were markedly reduced in C3-/-
      and Cfb-/- mice challenged with LPS. Ocular complement levels were also elevated
      in mice treated systemically with TLR2 and -3 ligands, injured by IVT injection
      or corneal debridement, or even in normal aging. IVT administration of a
      complement FD neutralizing antibody in rabbits inhibited LPS-induced complement
      activation in the posterior segment of the eye, but not in the anterior segment
      of the eye or in plasma. Conclusions: Systemic TLR stimulation and eye tissue
      injury induced time-dependent alternative complement pathway activation in the
      eye. Ocular complement levels were also gradually elevated during aging. An anti
      FD antibody IVT potently inhibited LPS-induced complement activation in the
      posterior segment of the eye. This study provides insights into the dynamic
      profile of ocular complement activation, which is valuable for complement
      research in eye diseases and for developing complement therapeutics for AMD.

PMID- 29450542
TI  - Optical Properties Influence Visual Cortical Functional Resolution After Cataract
      Surgery and Both Dissociate From Subjectively Perceived Quality of Vision.
AB  - Purpose: To investigate the relation between optical properties, population
      receptive fields (pRFs), visual function, and subjectively perceived quality of
      vision after cataract surgery. Methods: The study includes 30 patients who had
      recently undergone bilateral sequential cataract surgery. We used functional
      magnetic resonance imaging and pRF modelling methods to assess pRF sizes across
      visual cortical regions (V1-V3). Subjects also performed a complete
      ophthalmologic and psychophysical examination and answered a quality of vision
      questionnaire. Results: Subjects with worse optical properties had, as predicted,
      larger pRF sizes. In addition, analysis in the primary visual cortex revealed
      significantly larger mean pRF sizes for operated subjects with worse contrast
      sensitivity (P = 0.038). In contrast, patients who scored high in the subjective
      "bothersome" dimension induced by dysphotic symptoms had surprisingly lower pRF
      size fitting interception (P = 0.012) and pRF size fitting slopes (P = 0.020),
      suggesting a dissociation between objective quality of vision and subjective
      appraisal. Conclusions: Optical properties of the eye influence pRF size. In
      particular, visual aberrations have a negative impact on visual cortical
      processing. A novel dissociation between subjective reports of quality of vision
      and pRF sizes was further identified. This suggests that patients with better
      cortical resolution may have a negative subjective response possibly because of
      improved perception of dysphotic phenomena. pRF properties represent a valuable
      quantitative measure to objectively evaluate quality of vision but do not
      necessarily predict subjective complaints.

PMID- 29450543
TI  - Mutation in the Zebrafish cct2 Gene Leads to Abnormalities of Cell Cycle and Cell
      Death in the Retina: A Model of CCT2-Related Leber Congenital Amaurosis.
AB  - Purpose: The compound heterozygous mutations in the beta subunit of chaperonin
      containing TCP-1 (CCT), encoded by CCT2, lead to the Leber congenital amaurosis
      (LCA). In this study, a cct2 mutant line of zebrafish was established to
      investigate the role of CCT2 mutations in LCA in vertebrates. Methods: A cct2
      mutant zebrafish line was produced using the CRISPR-Cas9 system. Changes in the
      eyes of developing wild-type and mutant larvae were monitored using microscopy,
      immunostaining, TUNEL, and EdU assays. Phenotypic rescue of mutant phenotype was
      investigated by injection of CCT2 RNA into zebrafish embryos. Results: The cct2
      mutation (L394H-7del) led to the synthesis of a mutated cctbeta protein with the
      L394H replacement and deletion of 7 amino acid residues (positions 395-401). The
      homozygous cct2-L394H-7del mutant exhibited a small eye phenotype at 2 days post
      fertilization (dpf) and was embryonically lethal after 5 dpf. In homozygous cct2
      L394H-7del mutants, the retinal ganglion cell differentiation was attenuated,
      retinal cell cycle was affected, and the neural retinal cell death was
      significantly increased at 2 dpf compared with wild-type. Injection of RNA
      encoding wild-type human CCTbeta rescued the small eye phenotype, reduced retinal
      cell death, and restored the levels of CCTbeta protein and the major client
      protein Gbeta1 that were significantly reduced in the homozygous cct2-L394H-7del
      mutant compared with wild-type. These results indicate that cct2 plays an
      essential role in retinal development by regulating the cell cycle. Conclusions:
      The retinal pathology observed in the homozygous cct2-L394H-7del mutants
      resembles the retinal pathology of human LCA patients.

PMID- 29450545
TI  - Use of the Posterior/Anterior Corneal Curvature Radii Ratio to Improve the
      Accuracy of Intraocular Lens Power Calculation: Eom's Adjustment Method.
AB  - Purpose: To evaluate the accuracy of IOL power calculation using adjusted corneal
      power according to the posterior/anterior corneal curvature radii ratio. Methods:
      Nine hundred twenty-eight eyes from 928 reference subjects and 158 eyes from 158
      cataract patients who underwent phacoemulsification surgery were enrolled.
      Adjusted corneal power of cataract patients was calculated using the fictitious
      refractive index that was obtained from the geometric mean posterior/anterior
      corneal curvature radii ratio of reference subjects and adjusted anterior and
      predicted posterior corneal curvature radii from conventional keratometry (K)
      using the posterior/anterior corneal curvature radii ratio. The median absolute
      error (MedAE) based on the adjusted corneal power was compared with that based on
      conventional K in the Haigis and SRK/T formulae. Results: The geometric mean
      posterior/anterior corneal curvature radii ratio was 0.808, and the fictitious
      refractive index of the cornea for a single Scheimpflug camera was 1.3275. The
      mean difference between adjusted corneal power and conventional K was 0.05
      diopter (D). The MedAE based on adjusted corneal power (0.31 D in the Haigis
      formula and 0.32 D in the SRK/T formula) was significantly smaller than that
      based on conventional K (0.41 D and 0.40 D, respectively; P < 0.001 and P <
      0.001, respectively). The percentage of eyes with refractive prediction error
      within +/- 0.50 D calculated using adjusted corneal power (74.7%) was
      significantly greater than that obtained using conventional K (62.7%) in the
      Haigis formula (P = 0.029). Conclusions: IOL power calculation using adjusted
      corneal power according to the posterior/anterior corneal curvature radii ratio
      provided more accurate refractive outcomes than calculation using conventional K.

PMID- 29450544
TI  - HLA Class I Antigen Expression in Conjunctival Melanoma Is Not Associated With PD
      L1/PD-1 Status.
AB  - Purpose: Antitumor T cells need expression of HLA class I molecules but can be
      inhibited by ligands such as programmed death ligand 1 (PD-L1). We determined
      expression and regulation of these molecules in human conjunctival melanoma (CM)
      samples, cell lines, and murine xenografts. Methods: Immunofluorescence staining
      was performed to examine the expression of HLA-A, HLA-B/C, and beta-2
      microglobulin (B2M) in 23 primary CM samples. HLA class I expression was compared
      with clinicopathologic characteristics, the presence of tumor-infiltrating
      leukocytes, and PD-L1/PD-1 status. The effect of interferon gamma (IFN-gamma) on
      HLA class I expression was tested on three CM cell lines using quantitative PCR
      and flow cytometry. Furthermore, HLA class I expression was determined in CM cell
      line-derived murine xenografts. Results: One third of tumors had positive HLA-A,
      HLA-B/C, and B2M expression. A positive expression was especially seen in thin
      and epibulbar tumors but was not associated with recurrences. HLA class I
      expression was correlated with M2 macrophage density and tended to associate with
      CD8+ T-cell density but was independent of PD-L1 or PD-1 expression. IFN-gamma
      upregulated HLA class I expression and genes involved in HLA transcription and
      transportation on CM cell lines. Murine xenografts showed a comparable HLA class
      I expression as their respective cell lines. Conclusions: Our data indicate that
      subsets of CM have positive HLA class I expression, and HLA class I and PD-L1/PD
      1 are expressed independently. When one considers immunotherapy, one should also
      analyze HLA class I expression, whose downregulation can limit the efficacy of T
      cell-mediated therapies.

PMID- 29450550
TI  - Error in Data in the Results Section.

PMID- 29450546
TI  - A Plasma Metabolomic Signature of the Exfoliation Syndrome Involves Amino Acids,
      Acylcarnitines, and Polyamines.
AB  - Purpose: To determine the plasma metabolomic signature of the exfoliative
      syndrome (XFS), the most common cause worldwide of secondary open-angle glaucoma.
      Methods: We performed a targeted metabolomic study, using the standardized p180
      Biocrates Absolute IDQ p180 kit with a QTRAP 5500 mass spectrometer, to compare
      the metabolomic profiles of plasma from individuals with XFS (n = 16), and an age
      and sex-matched control group with cataract (n = 18). Results: A total of 151
      metabolites were detected correctly, 16 of which allowed for construction of an
      OPLS-DA model with a good predictive capability (Q2cum = 0.51) associated with a
      low risk of over-fitting (permQ2 = -0.48, CV-ANOVA P-value <0.001). The
      metabolites contributing the most to the signature were octanoyl-carnitine (C8)
      and decanoyl-carnitine (C10), the branched-chain amino acids (i.e., isoleucine,
      leucine, and valine), and tyrosine, all of which were at higher concentrations in
      the XFS group, whereas spermine and spermidine, together with their precursor
      acetyl-ornithine, were at lower concentrations than in the control group.
      Conclusions: We identified a significant metabolomic signature in the plasma of
      individuals with XFS. Paradoxically, this signature, characterized by lower
      concentrations of the neuroprotective spermine and spermidine polyamines than in
      controls, partially overlaps the plasma metabolomic profile associated with
      insulin resistance, despite the absence of evidence of insulin resistance in XFS.

PMID- 29450547
TI  - Aflibercept Action in a Rabbit Model of Chronic Retinal Neovascularization:
      Reversible Inhibition of Pathologic Leakage With Dose-Dependent Duration.
AB  - Purpose: We establish and characterize the chronic retinal neovascularization
      (RNV) induced by intravitreal (IVT) injection of DL-alpha-aminoadipic acid (AAA)
      in a rabbit model and investigate the extent and duration of inhibitory actions
      induced by IVT aflibercept on the RNV. Methods: Rabbits received a single IVT
      injection of AAA, with weekly follow-up fundus photography, fluorescein
      angiography (FA), and optical coherence tomography (OCT). After 10 weeks, they
      received a single IVT aflibercept or control injection. RNV leakage was
      quantified from FA by image analysis with Photoshop. Some eyes were collected for
      histologic analysis. Results: IVT AAA produced neuronal degeneration over a large
      fraction of the retina. RNV formed in the damaged area and by 10 weeks exhibited
      stable morphology and leakage, which persisted for at least 65 weeks. Control IVT
      injections did not affect RNV leakage, but IVT aflibercept completely blocked RNV
      leakage. The inhibition was reversible (i.e., the leakage returned as the drug
      cleared), and the duration of antileak effects with 500 MUg aflibercept was
      approximately 8 weeks. Partial regression of the pathologic vasculature also
      occurred with aflibercept, with reestablishment as the drug cleared. Conclusions:
      This model mimics a chronic human disease in its stability and persistence, and
      the antileak action of aflibercept is fully reversible with a dose-dependent
      duration. Therefore, this large eye model is uniquely suitable for investigations
      into the efficacy and duration of action of novel formulations and
      pharmacotherapies for retinal vascular diseases, and for studying the underlying
      pathobiology of retinal angiogenesis.

PMID- 29450552
TI  - Were Wolves Meet Dermatology.

PMID- 29450553
TI  - Harvey, Irma, and Maria-The Dermatologic Risks of Hurricanes and Floods.

PMID- 29450554
TI  - Colors Beyond the Visible.

PMID- 29450556
TI  - Pyotr Vasilyevich Nikolsky-The Man Behind the Sign.

PMID- 29450555
TI  - Caught in a Bind.

PMID- 29450557
TI  - Eczema's Big Break in Hollywood.

PMID- 29450560
TI  - [ECG results: tips and tricks for the correct diagnosis : Bradycardia and
      tachycardia rhythm disorders].
AB  - The 12-lead surface electrocardiogram (ECG) is of great importance for the
      diagnostics of cardiac arrhythmias. For the correct and systematic analysis it
      has a sensitivity and specificity for the correct diagnosis of supraventricular
      tachycardia or ventricular tachycardia of more than 95%. Nevertheless, the
      assessment of cardiac rhythm disorders is difficult for many physicians. In this
      way errors can occur, frequently due to a non-systematic analysis of the ECG;
      therefore, the aim of this article is to present the techniques and the necessary
      knowledge for assessment of the most frequent bradycardiac and tachycardiac heart
      rhythm disorders. Additionally, special features in the analysis of the ECG
      results in children are discussed.

PMID- 29450561
TI  - Cognitive performance of patients with chronic heart failure on
      sacubitril/valsartan : A retrospective cohort study.
AB  - BACKGROUND: Sacubitril, a neprilysin inhibitor in the combination molecule
      sacubitril/valsartan, slows down degradation of endogenous natriuretic peptides,
      thereby enhancing their beneficial cardiovascular effects. However, sacubitril
      might also promote neuronal dysfunction and cognitive impairment in patients with
      chronic heart failure (CHF) treated with sacubitril/valsartan, due to possible
      neprilysin inhibition at the level of Central Nervous System. METHODS: A
      retrospective cohort study was undertaken to detect the effects exerted by
      sacubitril/valsartan on cognitive function in CHF patients. The patients'
      clinical data were examined for information provided in the Mini-Mental State
      Examination (MMSE), which was routinely administered during clinical visits at
      two centers from 15 March to 31 October 2017. Patients in the
      sacubitril/valsartan group had a clinical history of at least 3 months of
      continuous sacubitril/valsartan administration. The control group comprised CHF
      patients on conventional therapy not taking sacubitril/valsartan. In the between
      group comparison, patients were matched for mean age, educational level, sex,
      NYHA class, and comorbidities. In the present retrospective study only patients
      in NYHA class II-III were enrolled. RESULTS: The mean MMSE score was 22.72 +/-
      2.68 (mean +/- standard deviation [SD]) in the sacubitril/valsartan group (n = 51
      patients) vs. 21.96 +/- 2.73 (mean +/- SD) in the control group (n = 51; p =
      0.1572, independent samples t-test). Thus, a similar mild-to-moderate impairment
      in cognitive performance was found in the comparison between the two groups.
      CONCLUSION: In our study, we did not find any evidence of the alleged harmful
      influence of sacubitril/valsartan on cognitive function. Patients taking
      sacubitril/valsartan for at least 3 months had similar mean MMSE scores to
      control subjects.

PMID- 29450562
TI  - [Which typical foot fractures should the radiologist know?]
AB  - CLINICAL/METHODICAL ISSUE: Due to mechanical loading and the number of joints
      involved, fractures of the foot are among the most common fractures. STANDARD
      RADIOLOGICAL METHODS: X-ray is basis for diagnostic workup of all foot fractures.
      METHODICAL INNOVATIONS: For stress fractures, the additional use of magnetic
      resonance imaging (MRI) is indicated. Computed tomography (CT) can be used for
      preoperative imaging of intraarticular tarsal fractures. PERFORMANCE: Simple
      traumatic fractures can be reliably diagnosed by X-ray. On the other hand, there
      is a poor sensitivity for stress fractures. ACHIEVEMENTS: Using a combination of
      X-ray, MRI, and CT, it is possible to reliably diagnosis and classify foot
      fractures. PRACTICAL RECOMMENDATIONS: The first step to diagnose a foot fracture
      should be the X-ray. CT and MRI can also be used to detect intra-articular
      fractures and MRI can be used for stress fractures.

PMID- 29450563
TI  - [Surgical treatment of extra-articular femorocetabular impingment].

PMID- 29450564
TI  - [Influence of morbid obesity on morbidity after partial liver resection].

PMID- 29450565
TI  - Tissue distribution of gold and silver after subacute intravenous injection of co
      administered gold and silver nanoparticles of similar sizes.
AB  - Gold (AuNPs, 12.8 nm) and silver nanoparticles (AgNPs, 10 nm), mixed or separate,
      were injected into the caudal vein of male Sprague-Dawley rats for 4 weeks. The
      rats were allowed to recover for further 4 weeks to examine the differences in
      AuNP/AgNP tissue distribution and clearance. The size distribution of injected
      AuNPs and AgNPs were not statistically different. The dose groups (five males per
      group for the administration and three males for the recovery) consisted of seven
      divisions, i.e., control, AgNPs (with a low dose of 10 ug/kg/day, and, a high
      dose of 100 ug/kg/day), AuNPs (with a low dose of 10 ug/kg/day, and, a high dose
      of 100 ug/kg/day), as well as mixed AgNPs/AuNPs (with a low dose of 10/10
      ug/kg/day, and a high dose of 100/100 ug/kg/day). The AgNPs accumulated in a dose
      dependent manner in the liver, spleen, kidneys, lung, brain, testis or blood. Au
      concentration increased also in a dose-dependent manner in the liver, kidneys,
      spleen and lungs, but not in the brain, testis and blood. Ag concentration in the
      tissues increased dose-dependently after 4 weeks of AgNP/AuNP mixed
      administration, but to a much lower extent than those observed when they were
      administered separately. Ag concentration in the tissues after 4 weeks of
      AgNP/AuNP mixed administration cleared dose-dependently after 4 weeks of
      recovery. Au concentration in the tissues increased dose-dependently after 4
      weeks of AgNp/AuNP mixed administration, while Au concentration in the tissues
      did not clear as seen in Ag after 4 weeks recovery. Au concentration showed
      biopersistency or accumulation in the liver, kidneys, spleen and brain of the 4
      weeks of recovery. In conclusion, AgNPs and AuNPs showed different toxicokinetic
      properties and the mixed administration of AgNPs with AuNPs resulted in mutual
      reduction of their tissue distribution which appeared to be due to competitive
      inhibition. Furthermore, this subacute intravenous injection study has suggested
      that these nanoparticles were distributed to the organs in particulate instead of
      ionic forms.

PMID- 29450566
TI  - Unicompartmental knee arthroplasty fails to completely restore normal gait
      patterns during level walking.
AB  - PURPOSE: Gait analysis is a valuable instrument for measuring function
      objectively after unicompartmental knee arthroplasty (UKA). However, most gait
      analysis studies have reported conflicting results for functional assessment
      after UKA. This meta-analysis compared the gait patterns of UKA patients and
      healthy controls during level walking. METHODS: Studies were included in the meta
      analysis if they recorded vertical ground reaction force (GRF), flexion at
      initial contact, flexion at loading response, extension at mid-stance, flexion at
      swing, walking speed, cadence, and stride length in UKA patients or healthy
      controls. RESULTS: Seven studies met the criteria for inclusion in the meta
      analysis. The UKA patients and healthy controls were similar in terms of vertical
      GRF (95% CI - 0.54 to 0.23; ns), flexion at initial contact (95% CI - 0.47 to
      4.96; ns), flexion at loading response (95% CI - 1.29 to 3.69; ns), and flexion
      at swing (95% CI - 8.85 to 0.40; ns). In contrast, extension at mid-stance (95%
      CI 0.53 to 4.88; P = 0.01), walking speed (95% CI - 2.13 to - 0.15; P = 0.02),
      cadence (95% CI - 1.02 to - 0.25; P = 0.001), and stride length (95% CI - 2.02 to
      - 0.22; P = 0.01) differed significantly between groups. Subgroup analyses
      revealed that the pooled data were similar between groups: 1st maximum (heel
      strike), - 0.43 BW (ns); 1st minimum (mid-stance), 0.61 BW (ns); and 2nd maximum
      (toe off), - 0.46 BW (ns). CONCLUSIONS: There were no significant differences in
      vertical GRF or overall kinematics in the sagittal plane between UKA patients and
      healthy controls during level walking. However, the UKA group had a significantly
      slower walking speed and cadence and a shorter stride length than healthy
      controls. The current findings suggest that, clinically, UKA fails to completely
      restore normal gait patterns. LEVEL OF EVIDENCE: Level II, therapeutic study.

PMID- 29450567
TI  - Coronal tibial anteromedial tunnel location has minimal effect on knee
      biomechanics.
AB  - PURPOSE: Studies have found anatomic variation in the coronal position of the
      insertion site of anteromedial (AM) bundle of the anterior cruciate ligament
      (ACL) on the tibia, which can lead to questions about tunnel placement during ACL
      reconstruction. The purpose of this study was to determine how mediolateral
      placement of the tibial AM graft tunnel in double-bundle ACL reconstructions
      affects knee biomechanics. METHODS: Two different types of double-bundle ACL
      reconstructions were performed. The AM tibial tunnel was placed at either the
      medial or lateral portion of tibial AM footprint. Nine cadaveric knees were
      tested with the robotic/universal force-moment sensor system with the use of (1)
      an 89.0-N anterior tibial load at full extension (FE), 30 degrees , 60 degrees 
      and 90 degrees  of knee flexion and (2) a combined 7.0-Nm valgus torque and 5.0
      Nm internal tibial rotation torque at FE, 15 degrees , 30 degrees and 45 degrees 
      of knee flexion. RESULTS: Both medial (2.6 +/- 1.2 mm) and lateral (1.6 +/- 0.9
      mm) double-bundle reconstructions reduced the anterior tibial translation (ATT)
      to less than the intact value (3.9 +/- 0.7 mm) at FE. At all other flexion
      angles, there was no significant different in ATT between the intact knee and the
      reconstructions. At FE, the ATT for the medial AM reconstruction was different
      from that of the lateral AM construction and closer to the intact ACL value.
      CONCLUSION: The coronal tibial placement of the AM tunnel had only a slight
      effect on knee biomechanics. In patients with differing AM bundle coronal
      positions, the AM tibial tunnel can be placed anatomically at the native
      insertion site.

PMID- 29450570
TI  - Metals in Feathers of African Penguins (Spheniscus demersus): Considerations for
      the Welfare and Management of Seabirds Under Human Care.
AB  - Bird feathers have been proven to be reliable indicators of metal exposure
      originating from contaminated food and polluted environments. The concentrations
      of 15 essential and non-essential metals were investigated in African penguins
      (Spheniscus demersus) feathers from a Northwestern Italian zoological facility.
      These birds are exclusively fed with herring from the northeast Atlantic Ocean.
      Certain elements, such as Hg and Cd, reflected the bioaccumulation phenomena that
      occur through the marine food chain. The levels of Cr, Mn, and Ni were comparable
      to those registered in feathers of birds living in polluted areas. These results
      are important for comparative studies regarding the health, nutrition and welfare
      of endangered seabirds kept under human care.

PMID- 29450569
TI  - Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome.
AB  - AIMS/HYPOTHESIS: Diabetes is one of the cardinal features of thiamine-responsive
      megaloblastic anaemia (TRMA) syndrome. Current knowledge of this rare monogenic
      diabetes subtype is limited. We investigated the genotype, phenotype and response
      to thiamine (vitamin B1) in a cohort of individuals with TRMA-related diabetes.
      METHODS: We studied 32 individuals with biallelic SLC19A2 mutations identified by
      Sanger or next generation sequencing. Clinical details were collected through a
      follow-up questionnaire. RESULTS: We identified 24 different mutations, of which
      nine are novel. The onset of the first TRMA symptom ranged from birth to 4 years
      (median 6 months [interquartile range, IQR 3-24]) and median age at diabetes
      onset was 10 months (IQR 5-27). At presentation, three individuals had isolated
      diabetes and 12 had asymptomatic hyperglycaemia. Follow-up data was available for
      15 individuals treated with thiamine for a median 4.7 years (IQR 3-10). Four
      patients were able to stop insulin and seven achieved better glycaemic control on
      lower insulin doses. These 11 patients were significantly younger at diabetes
      diagnosis (p = 0.042), at genetic testing (p = 0.01) and when starting thiamine
      (p = 0.007) compared with the rest of the cohort. All patients treated with
      thiamine became transfusion-independent and adolescents achieved normal puberty.
      There were no additional benefits of thiamine doses >150 mg/day and no reported
      side effects up to 300 mg/day. CONCLUSIONS/INTERPRETATION: In TRMA syndrome,
      diabetes can be asymptomatic and present before the appearance of other features.
      Prompt recognition is essential as early treatment with thiamine can result in
      improved glycaemic control, with some individuals becoming insulin-independent.
      DATA AVAILABILITY: SLC19A2 mutation details have been deposited in the Decipher
      database ( https://decipher.sanger.ac.uk/ ).

PMID- 29450571
TI  - Evaluation of Fish Health Status and Histopathology in Gills and Liver Due to
      Metal Contaminated Sediments Exposure.
AB  - Health status of freshwater fish, Cirrhina mrigala was studied by qualitative and
      quantitative histopathological analysis, alterations in frequency/prevalence
      percentages (%) and histological alteration indices (HAI) in response to metal
      contaminated sediments of the River Ravi aquatic ecosystem. Histo-structures of
      gill and liver samples of fish were analyzed and comparison between the degree of
      damage of the alterations in fish organs was performed after exposure to metal
      contaminated sediments for 7, 14 and 28 days under semi-static water renewal
      bioassays. Histopathological studies revealed marked histological alterations in
      the gills and liver of exposed fish as compared to normal tissue structure
      observed in control fish. The frequency and prevalence percentages observed in 28
      day exposed fish were significantly higher as compared to 7- and 14-day exposed
      fish. The order of frequency and prevalence percentage for gills and liver of
      exposed fish was as: 28-day > 14-day > 7-day. The highest prevalence percentages
      recorded were 83 and 80% as focal area of necrosis in gill and liver,
      respectively, after 28-day exposure. The lowest prevalence percentage observed in
      7-day exposed Cirrhina mrigala was dilation of sinusoids (17%).

PMID- 29450572
TI  - Plant Genetics and Molecular Biology: An Introduction.
AB  - The rapidly evolving technologies can serve as a potential growth engine in
      agriculture as many of these technologies have revolutionized several industries
      in the recent past. The tremendous advancements in biotechnology methods, cost
      effective sequencing technology, refinement of genomic tools, and standardization
      of modern genomics-assisted breeding methods hold great promise in taking the
      global agriculture to the next level through development of improved climate
      smart seeds. These technologies can dramatically increase our capacity to
      understand the molecular basis of traits and utilize the available resources for
      accelerated development of stable high-yielding, nutritious, input-use efficient,
      and climate-smart crop varieties. This book aimed to document the monumental
      advances witnessed during the last decade in multiple fields of plant
      biotechnology such as genetics, structural and functional genomics, trait and
      gene discovery, transcriptomics, proteomics, metabolomics, epigenomics,
      nanotechnology, and analytical tools. This book will serve to update the
      scientific community, academicians, and other stakeholders in global agriculture
      on the rapid progress in various areas of agricultural biotechnology. This
      chapter provides a summary of the book, "Plant Genetics and Molecular Biology."
      Graphical Abstract.

PMID- 29450573
TI  - Author Correction: Beta cell connectivity in pancreatic islets: a type 2 diabetes
      target?
AB  - The original version of this article unfortunately contained a mistake. Legends
      of Figures 1 and 2 were interchanged. The correct versions are given below.

PMID- 29450574
TI  - Correction to: Volumetric absorptive microsampling as an alternative tool for
      therapeutic drug monitoring of first-generation anti-epileptic drugs.
AB  - We would like to call the reader's attention to the fact that unfortunately in
      fig. 2 of the original article the figure headings of both graphs are the same.

PMID- 29450575
TI  - Osteoblastomatosis: an unusual diagnosis and treatment.
AB  - Osteoblastomatosis (OBLT), also referred to as multifocal osteoblastoma (OB), is
      an unusual and recently described entity consisting of multifocal tumors
      histologically consistent with osteoblastoma and osteoid osteoma (OO) but
      radiologically mimicking a vascular bone lesion. OBLT treatment is based on
      aggressive procedures, such as amputation, en bloc resection, and chemotherapy.
      Only one previously reported case was successfully treated following a multimodal
      approach consisting of curettage, cryotherapy, intravenous bisphosphonates, and
      radiofrequency ablation. We present a case of OBLT that may have been cured by CT
      guided percutaneous radiofrequency ablation.

PMID- 29450577
TI  - Re: percutaneous nephrolithotomy-position, position, position!

PMID- 29450576
TI  - ImmunoPET imaging of CD38 in murine lymphoma models using 89Zr-labeled
      daratumumab.
AB  - PURPOSE: CD38 is considered a potential biomarker for multiple myeloma (MM) and
      has shown a strong link with chronic lymphocytic leukemia due to high and uniform
      expression on plasma cells. In vivo evaluation of CD38 expression may provide
      useful information about lesion detection and prognosis of treatment in MM. In
      this study, immunoPET imaging with 89Zr-labeled daratumumab was used for
      differentiation of CD38 expression in murine lymphoma models to provide a
      potential non-invasive method for monitoring CD38 in the clinic. METHODS:
      Daratumumab was radiolabeled with 89Zr (t1/2 = 78.4 h) via conjugation with
      desferrioxamine (Df). After Western blot (WB) was used to screen CD38 expression
      in five lymphoma cell lines, flow cytometry and cellular binding assays were
      performed to test the binding ability of labeled or conjugated daratumumab with
      CD38 in vitro. PET imaging and biodistribution studies were performed to evaluate
      CD38 expression after injection of 89Zr-Df-daratumumab. 89Zr-Df-IgG was also
      evaluated as a non-specific control group in the Ramos model. Finally, CD38
      expression in tumor tissues was verified by histological analysis. RESULTS: Using
      WB screening, the Ramos cell line was found to express the highest level of CD38
      while the HBL-1 cell line had the lowest expression. Df-conjugated and 89Zr
      labeled daratumumab displayed similar high binding affinities with Ramos cells.
      PET imaging of 89Zr-Df-daratumumab showed a high tumor uptake of up to 26.6 +/-
      8.0 %ID/g for Ramos at 120 h post-injection, and only up to 6.6 +/- 2.9 %ID/g for
      HBL-1 (n = 4). Additionally, 89Zr-Df-IgG demonstrated a low tumor uptake in the
      Ramos model (only 4.3 +/- 0.8 %ID/g at 120 h post-injection). Ex vivo
      biodistribution studies showed similar trends with imaging results.
      Immunofluorescence staining of tumor tissues verified higher CD38 expression of
      Ramos than that of HBL-1. CONCLUSIONS: The role of 89Zr-Df-daratumumab was
      investigated for evaluating CD38 expression in lymphoma models non-invasively and
      was found to be to a promising imaging agent of CD38-positive hematological
      diseases such as MM in future clinical applications.

PMID- 29450584
TI  - Dietary patterns and longitudinal change in hip bone mineral density among older
      men.
AB  - : Studying dietary patterns is often more informative than individual nutrients
      or foods. We found that a Prudent dietary pattern (rich in vegetables and fish)
      was associated with reduced loss of total hip BMD in older men. A Prudent dietary
      pattern may be a potential lifestyle strategy for minimizing bone loss.
      INTRODUCTION: This study aimed to identify baseline dietary patterns using factor
      analysis in a cohort of older men and to evaluate whether the dietary patterns
      were associated with bone mineral density change (%DeltaBMD) at the total hip and
      femoral neck over time. METHODS: Participants (n = 4379; mean age 72.9 +/- 5.5
      years) were from the Osteoporotic Fractures in Men (MrOS) prospective cohort
      study and had dietary data collected at baseline (March 2000-April 2002) and BMD
      measured at baseline and Visit 2 (March 2005-May 2006). Dietary intake was
      assessed with a brief Block food frequency questionnaire (FFQ); factor analysis
      was used to derive dietary patterns. BMD was measured by dual-energy x-ray
      absorptiometry (DXA); %DeltaBMD was calculated from baseline to Visit 2. We used
      generalized linear regression to estimate least square (LS) means of %DeltaBMD in
      quartiles of the dietary pattern scores adjusted for potential confounding
      factors. RESULTS: Two major dietary patterns were derived: Prudent (abundant in
      vegetables, salad, and non-fried fish) and Western (rich in hamburger, fries,
      processed meats, cheese, and sweets/desserts). There was an inverse association
      between adherence to the Prudent pattern and total hip %DeltaBMD (p-trend = 0.028
      after adjusting for age and clinical site; p-trend = 0.033 after further
      adjustment for smoking, calcium supplement use, diabetes, hypertension, and total
      energy intake). No other consistent associations between dietary patterns and
      %DeltaBMD were observed. CONCLUSIONS: Greater adherence to a Prudent dietary
      pattern may attenuate total hip BMD loss (%DeltaBMD) in older men.

PMID- 29450585
TI  - Effect of isolated vitamin D supplementation on bone turnover markers in younger
      postmenopausal women: a randomized, double-blind, placebo-controlled trial.
AB  - : Vitamin D (VD) plays an important role in bone mineralization. The present
      study investigates the effect of VD supplementation alone on bone turnover
      markers in younger postmenopausal women. It has been shown that VD
      supplementation in postmenopausal women with hypovitaminosis D is associated with
      a reduction in bone turnover markers. PURPOSE: The purpose of this study is to
      evaluate the effect of VD supplementation alone on bone turnover markers in
      younger postmenopausal women. METHODS: In this double-blind, placebo-controlled
      trial, 160 women were randomized into the VD group (supplementation with 1000 IU
      of vitamin D3/day, orally; n = 80) or placebo group (n = 80). Women aged 50-65
      years with amenorrhea >= 12 months and normal bone mineral density were included.
      The intervention lasted 9 months, and the participants were assessed at the
      beginning and end of treatment. Serum levels of total calcium, parathormone
      (PTH), alkaline phosphatase (AP), and 24-h urine calcium were determined. Serum C
      terminal telopeptide of type I collagen (s-CTX) and procollagen type 1 N-terminal
      propeptide (P1NP) were measured by immunoassay as markers of bone resorption and
      formation, respectively. Plasma 25-hydroxyvitamin-D [25(OH)D] concentrations were
      measured by HPLC. Intention-to-treat analysis was performed using ANOVA,
      Student's t test, Tukey's test, and gamma distribution. RESULTS: Over the period
      of 9 months, 25(OH)D concentrations increased from 15.0 +/- 7.5 to 27.5 +/- 10.4
      ng/mL (+ 45.4%) in the VD group and decreased from 16.9 +/- 6.7 to 13.8 +/- 6.0
      ng/mL (- 18.5%) in the placebo group (p < 0.001). There was a decrease (- 21.3%)
      of PTH levels in the VD group with a significant difference between groups at the
      end of the study (p < 0.001). No significant differences were observed in the
      other laboratory parameters (total calcium, AP, and calciuria) in either group (p
      > 0.05). A comparison of bone turnover markers showed a significant reduction in
      of s-CTX (- 24.2%, p < .0001) and P1NP (- 13.4%, p = 0.003) levels in the VD
      group. No significant variations in bone turnover markers were observed in the
      placebo group (s-CTX, - 6.9%, p = 0.092 and P1NP, - 0.6%, p = 0.918). CONCLUSION:
      In younger postmenopausal women with VD deficiency, isolated supplementation with
      1000 IU of vitamin D3 for 9 months is associated with a reduction in bone
      turnover markers. However, any between-group differences was not observed in bone
      turnover markers.

PMID- 29450587
TI  - Morphogenetic Alterations in Melipona quadrifasciata anthidioides (Hymenoptera:
      Apidae) Associated with Pesticides.
AB  - Bees are major pollinators of both native flora and cultured crops. Nonetheless,
      despite their key functional role in ecosystems and agriculture, bee populations
      have been affected worldwide by deforestation and contamination by insecticides.
      Conversely, little is known about the effects of pesticides on morphogenetic
      development of neotropical stingless bees. We compared the fluctuating asymmetry
      (FA) in newly emerged bees and foragers of Melipona quadrifasciata anthidioides
      exposed to pesticides (experimental greenhouse and cultivated field). In
      addition, visitation behavior of foragers was inferred from pollen analyses and
      direct observation. A significant increase of FA (P < 0.001) was detected in bees
      from the greenhouse. Even though pesticides might affect their development,
      foragers seem to avoid contaminated plants whenever possible, as confirmed by
      pollen and visitation analyses. Consequently, the conservation of natural forests
      in agricultural landscapes is essential to ensure the health of colonies in
      stingless bees.

PMID- 29450586
TI  - The host control of a clinical isolate strain of P. aeruginosa infection is
      independent of Nod-1 but depends on MyD88.
AB  - OBJECTIVE AND DESIGN: The objective of this study was to investigate the role of
      Nod1 in the recruitment of neutrophils into the infection site and in the
      establishment of the inflammatory response elicited by a clinical isolate strain
      of P. aeruginosa in vivo, while comparing it to the well-established role of
      MyD88 in this process. SUBJECTS: Wild-type, Nod1-/- and MyD88-/- mice, all with a
      C57Bl/6 background. METHODS: Mice were intranasally infected with Pseudomonas
      aeruginosa DZ605. Bronchoalveolar lavage and blood were harvested 6 or 20 h post
      infection for evaluating bacterial load, chemokine levels and neutrophil
      migration. Survival post-infection was also observed. RESULTS: We show here that
      wild-type and Nod1-/- mice induce similar lung chemokine levels, neutrophil
      recruitment, and bacterial load, thus leading to equal survival rates upon P.
      aeruginosa pulmonary infection. Furthermore, we confirmed the essential role of
      MyD88-dependent signalling in recruiting neutrophils and controlling P.
      aeruginosa-induced pulmonary infection. CONCLUSION: The results suggest that in
      contrast to MyD88, under our experimental conditions, the absence of Nod1 does
      not impair the recruitment of neutrophils in response to P. aeruginosa DZ605.

PMID- 29450588
TI  - Response rates and recurrence patterns after low-dose radiotherapy with 4 Gy in
      patients with low-grade lymphomas.
AB  - PURPOSE: Retrospective study of effectiveness, toxicity, and relapse patterns
      after low-dose radiotherapy (LDRT) in patients with low-grade lymphomas. METHODS:
      47 patients (median age 64 years) with 50 lesions were treated with LDRT (2 * 2
      Gy). In 60%, LDRT was the primary and curative treatment, in 40% offered as
      second-line therapy in recurrent disease. Histology included follicular (57%) and
      marginal zone lymphomas (43%). Patients were followed-up regularly clinically
      (skin) and with CT or MRI scans. RESULTS: Median follow-up was 21 months. 84% of
      the lesions were extranodal disease (32% orbit, 14% salivary glands, 30% skin,
      and 8% others). Most lesions were <=5 cm (90%) with a singular affection (74%).
      26% of the patients received rituximab simultaneously. Overall response rate
      (ORR) was 90% (all lesions), 93.3% (primary treatment), and 85% (recurrence
      treatment); p = 0.341. 2-year Local progression-free survival (LPFS) for all,
      curative, and palliative patients was 91.1%, 96.7%, and 83.8%, respectively; p =
      0.522. Five relapses were detected: three infield only, and were therefore
      treated with LDRT or subsequent local RT of 30 Gy. Two patients showed an in- and
      outfield progression and were consequently treated with chemotherapy. Predictive
      factors for higher LPFS were tumor size <=5 cm (p = 0.003), <=2 previous
      treatments (p = 0.027), no skin involvement (p = 0.05), singular affection (p =
      0.075), and simultaneous rituximab application (p = 0.148). LDRT was tolerated
      well, without detectable acute or long-term side effects. CONCLUSION: Primary
      LDRT is an effective treatment with high ORR and long-lasting remissions in a
      subset of patients with low-grade lymphoma, and may therefore be a curative
      treatment option for patients with low tumor burden. LDRT with the CD20 antibody
      obinutuzumab will soon be tested in a prospective multicenter trial.

PMID- 29450589
TI  - Effect of continuous positive airway pressure administration during lung
      stereotactic ablative radiotherapy: a comparative planning study.
AB  - PURPOSE: By increasing lung volume and decreasing respiration-induced tumour
      motion amplitude, administration of continuous positive airway pressure (CPAP)
      during stereotactic ablative radiotherapy (SABR) could allow for better sparing
      of the lungs and heart. In this study, we evaluated the effect of CPAP on lung
      volume, tumour motion amplitude and baseline shift, as well as the dosimetric
      impact of the strategy. METHODS: Twenty patients with lung tumours referred for
      SABR underwent 4D-computed tomography (CT) scans with and without CPAP
      (CPAP/noCPAP) at two timepoints (T0/T1). First, CPAP and noCPAP scans were
      compared for lung volume, tumour motion amplitude, and baseline shift. Next, CPAP
      and noCPAP treatment plans were computed and compared for lung dose parameters
      (mean lung dose (MLD), lung volume receiving 20 Gy (V20Gy), 13 Gy (V13Gy), and 5
      Gy (V5Gy)) and mean heart dose (MHD). RESULTS: On average, CPAP increased lung
      volume by 8.0% (p < 0.001) and 6.3% (p < 0.001) at T0 and T1, respectively, but
      did not change tumour motion amplitude or baseline shift. As a result, CPAP
      administration led to an absolute decrease in MLD, lung V20Gy, V13Gy and V5Gy of
      0.1 Gy (p = 0.1), 0.4% (p = 0.03), 0.5% (p = 0.04) and 0.5% (p = 0.2),
      respectively, while having no significant influence on MHD. CONCLUSIONS: In
      patients referred for SABR for lung tumours, CPAP increased lung volume without
      modifying tumour motion or baseline shift. As a result, CPAP allowed for a slight
      decrease in radiation dose to the lungs, which is unlikely to be clinically
      significant.

PMID- 29450591
TI  - Occurrence of pneumonitis following radiotherapy of breast cancer - A prospective
      study.
AB  - AIM: of this study is to determine the temporal resolution of therapy-induced
      pneumonitis, and to assess promoting factors in adjuvant treated patients with
      unilateral mammacarcinoma. PATIENTS AND METHODS: A total of 100 post-surgery
      patients were recruited. The cohort was treated by 2 field radiotherapy (2FRT;
      breast and chest wall, N = 75), 3 field radiotherapy (3FRT; + supraclavicular
      lymphatic region, N = 8), or with 4 field radiotherapy (4FRT; + parasternal
      lymphatic region, N = 17). Ninety-one patients received various systemic
      treatments prior to irradiation. Following an initial screening visit post-RT,
      two additional visits after 12 and 25 weeks were conducted including radiographic
      examination. In addition, general anamnesis and the co-medication were recorded.
      The endpoint was reached as soon as a pneumonitis was developed or at maximum of
      six months post-treatment. RESULTS: A pneumonitis incidence of 13% was
      determined. Of 91 patients with prior systemic therapy, 11 patients developed
      pneumonitis. Smoking history and chronic obstructive pulmonary disease (COPD)
      appeared to be positive predictors, whereas past pneumonia clearly promoted
      pneumonitis. Further pneumonitis-promoting predictors are represented by the
      applied field extensions (2 field radiotherapy [2FRT] < 3 field radiotherapy
      [3FRT] < 4 field radiotherapy [4FRT]) and the type of combined initial systemic
      therapies. As a consequence, all of the three patients in the study cohort
      treated with 4FRT and initial chemotherapy combined with anti-hormone and
      antibody protocols developed pneumonitis. A combination of the hormone
      antagonists tamoxifen and goserelin might enhance the risk for pneumonitis.
      Remarkably, none of the 11 patients co-medicated with statins suffered from
      pneumonitis. CONCLUSIONS: The rapidly increasing use of novel systemic therapy
      schedules combined with radiotherapy (RT) needs more prospective studies with
      larger cohorts. Our results indicate that contribution to pneumonitis occurrence
      of various (neo)adjuvant therapy approaches followed by RT is of minor relevance,
      whereas mean total lung doses of >10 Gy escalate the risk of lung tissue
      complications. The validity of potential inhibitors of therapy-induced
      pneumonitis as observed for statin co-medication should further be investigated
      in future trials.

PMID- 29450592
TI  - Under-reported dosimetry errors due to interplay effects during VMAT dose
      delivery in extreme hypofractionated stereotactic radiotherapy.
AB  - BACKGROUND AND PURPOSE: Radiotherapy of extracranial metastases changed from
      normofractioned 3D CRT to extreme hypofractionated stereotactic treatment using
      VMAT beam techniques. Random interaction between tumour motion and dynamically
      changing beam parameters might result in underdosage of the CTV even for an
      appropriately dimensioned ITV (interplay effect). This study presents a clinical
      scenario of extreme hypofractionated stereotactic treatment and analyses the
      impact of interplay effects on CTV dose coverage. METHODS: For a
      thoracic/abdominal phantom with an integrated high-resolution detector array
      placed on a 4D motion platform, dual-arc treatment plans with homogenous target
      coverage were created using a common VMAT technique and delivered in a single
      fraction. CTV underdosage through interplay effects was investigated by comparing
      dose measurements with and without tumour motion during plan delivery. RESULTS:
      Our study agrees with previous works that pointed out insignificant interplay
      effects on target coverage for very regular tumour motion patterns like simple
      sinusoidal motion. However, we identified and illustrated scenarios that are
      likely to result in a clinically relevant CTV underdosage. For tumour motion with
      abnormal variability, target coverage quantified by the CTV area receiving more
      than 98% of the prescribed dose decreased to 78% compared to 100% at static dose
      measurement. CONCLUSION: This study is further proof of considerable influence of
      interplay effects on VMAT dose delivery in stereotactic radiotherapy. For
      selected conditions of an exemplary scenario, interplay effects and related
      motion-induced target underdosage primarily occurred in tumour motion pattern
      with increased motion variability and VMAT plan delivery using complex MLC dose
      modulation.

PMID- 29450595
TI  - Vascular-induced lung injury: another advocate for personalized ARDS management :
      Discussion on "Inspiratory preload obliteration may injure lungs via cyclical 'on
      off' vascular flow".

PMID- 29450594
TI  - Position paper for the organization of ECMO programs for cardiac failure in
      adults.
AB  - Extracorporeal membrane oxygenation (ECMO) has been used increasingly for both
      respiratory and cardiac failure in adult patients. Indications for ECMO use in
      cardiac failure include severe refractory cardiogenic shock, refractory
      ventricular arrhythmia, active cardiopulmonary resuscitation for cardiac arrest,
      and acute or decompensated right heart failure. Evidence is emerging to guide the
      use of this therapy for some of these indications, but there remains a need for
      additional evidence to guide best practices. As a result, the use of ECMO may
      vary widely across centers. The purpose of this document is to highlight key
      aspects of care delivery, with the goal of codifying the current use of this
      rapidly growing technology. A major challenge in this field is the need to
      emergently deploy ECMO for cardiac failure, often with limited time to assess the
      appropriateness of patients for the intervention. For this reason, we advocate
      for a multidisciplinary team of experts to guide institutional use of this
      therapy and the care of patients receiving it. Rigorous patient selection and
      careful attention to potential complications are key factors in optimizing
      patient outcomes. Seamless patient transport and clearly defined pathways for
      transition of care to centers capable of providing heart replacement therapies
      (e.g., durable ventricular assist device or heart transplantation) are essential
      to providing the highest level of care for those patients stabilized by ECMO but
      unable to be weaned from the device. Ultimately, concentration of the most
      complex care at high-volume centers with advanced cardiac capabilities may be a
      way to significantly improve the care of this patient population.

PMID- 29450596
TI  - [Strategies for a regenerative therapy of hearing loss. German version].
AB  - Despite impressive technical progress in the field of conventional hearing aids
      and implantable hearing systems, the hopes for the treatment of inner ear
      diseases such as hearing loss and tinnitus have become increasingly directed
      toward regenerative therapeutic approaches. This review discusses the currently
      most promising strategies for hair cell regeneration in the inner ear to treat
      hearing loss, including stem cell-based, gene transfer-based, and pharmacological
      interventions. Furthermore, previous milestones and ground-breaking work in this
      scientific field are identified. After many years of basic research, the first
      clinical trials with a regenerative therapeutic approach for hearing-impaired
      patients were recently initiated. Although there is still a long and bumpy road
      ahead until a true breakthrough is achieved, it seems more realistic than ever
      that regenerative therapies for the inner ear will find their way into clinical
      practice.

PMID- 29450597
TI  - Unenhanced 320-row multidetector computed tomography of the brain in children:
      comparison of image quality and radiation dose among wide-volume, one-shot
      volume, and helical scan modes.
AB  - BACKGROUND: The 320-row multidetector computed tomography (CT) scanner has
      multiple scan modes, including volumetric modes. OBJECTIVE: To compare the image
      quality and radiation dose of 320-row CT in three acquisition modes - helical,
      one-shot volume, and wide-volume scan - at pediatric brain imaging. MATERIALS AND
      METHODS: Fifty-seven children underwent unenhanced brain CT using one of three
      scan modes (helical scan, n=21; one-shot volume scan, n=17; wide-volume scan,
      n=19). For qualitative analysis, two reviewers evaluated overall image quality
      and image noise using a 5-point grading system. For quantitative analysis, signal
      to-noise ratio, image noise and posterior fossa artifact index were calculated.
      To measure the radiation dose, adjusted CT dose index per unit volume (CTDIadj)
      and dose length product (DLP) were compared. RESULTS: Qualitatively, the wide
      volume scan showed significantly less image noise than the helical scan
      (P=0.009), and less streak artifact than the one-shot volume scan (P=0.001). The
      helical mode showed significantly lower signal-to-noise ratio, with a higher
      image noise level compared with the one-shot volume and wide-volume modes (all
      P<0.05). The CTDIadj and DLP were significantly lower in the one-shot volume and
      wide-volume modes compared with those in the helical scan mode (all P<0.05).
      CONCLUSION: For pediatric unenhanced brain CT, both the wide-volume and one-shot
      volume scans reduced radiation dose compared to the helical scan mode, while the
      wide-volume scan mode showed fewer streak artifacts in the skull vertex and
      posterior fossa than the one-shot volume scan.

PMID- 29450598
TI  - Validity of police contacts as a performance indicator for the public mental
      health care system in Amsterdam: an open cohort study.
AB  - PURPOSE: The Public Mental Health Care (PMHC) system is a network of public
      services and care- and support institutions financed from public funds.
      Performance indicators based on the registration of police contacts could be a
      reliable and useful source of information for the stakeholders of the PMHC system
      to monitor performance. This study aimed to provide evidence on the validity of
      using police contacts as a performance indicator to assess the continuity of care
      in the PMHC system. METHODS: Data on services received, police contacts and
      detention periods of 1928 people that entered the PMHC system in the city of
      Amsterdam were collected over a period of 51 months. Continuity of care was
      defined as receiving more than 90 days of uninterrupted service. The associations
      between police contacts and continuity were analyzed with multilevel Poisson and
      multivariate linear regression modeling. RESULTS: Clients had on average 2.12
      police contacts per person-year. Clients with police contacts were younger, more
      often single, male, and more often diagnosed with psychiatric or substance abuse
      disorders than clients without police contacts. Incidence rates of police
      contacts were significantly lower for clients receiving continuous care than for
      clients receiving discontinuous care. The number of police contacts of clients
      receiving PMHC coordination per month was found to be a significant predictor of
      the percentage of clients in continuous care. CONCLUSION: The number of police
      contacts of clients can be used as a performance indicator for an urban PMHC
      system to evaluate the continuity of care in the PMHC system.

PMID- 29450599
TI  - A typology of satisfaction with mental health services based on Andersen's
      behavioral model.
AB  - OBJECTIVE: Patients with mental disorders (MDs) form a highly heterogeneous
      group, whose satisfaction with mental health services (MHS) may vary according to
      different variables. Identifying patient subgroups with similar levels of
      satisfaction may help identify variables that contribute to satisfaction or
      dissatisfaction with services. This study established a typology of patient
      satisfaction with MHS that revealed variables specific to each group. METHODS:
      The study included 325 patients with MDs across four health service networks
      offering integrated and diversified services. Data were collected using five
      standardized instruments, and participant medical records. A conceptual framework
      was developed, based on Andersen's Behavioral Model, which integrates socio
      demographic, clinical, needs-related and service use variables. Using cluster
      analysis, a typology of patient satisfaction was created. RESULTS: Analyses
      yielded four patient clusters: two where levels of satisfaction were relatively
      high and two with lower levels of satisfaction (range 3.74-4.37). Greater care
      continuity and higher income related to greater patient satisfaction; whereas co
      occurring MDs and substance use disorders (SUD), as well as more numerous and
      severe needs, characterized dissatisfied patients who were frequent users of MHS.
      CONCLUSIONS: Results highlight the need for continuity of care and adequate socio
      economic conditions for increasing patient satisfaction with MHS. Lower levels of
      satisfaction among patients with common MDs and SUDs suggest the importance of
      addressing their specific needs to enhance satisfaction and MH recovery.

PMID- 29450600
TI  - Sexual orientation disparities in the co-occurrence of substance use and
      psychological distress: a national population-based study (2008-2015).
AB  - PURPOSE: Although strong evidence documents the elevated prevalence of both
      substance use and mental health problems among sexual minorities (i.e., gay,
      lesbian, and bisexuals), relatively less research has examined whether risk of
      the co-occurrence of these factors is elevated among sexual minorities compared
      to heterosexuals. The object of this study was to (1) explore sexual orientation
      based differences in substance use, psychological distress, and their co
      occurrence in a representative sample in Sweden, and (2) examine if greater
      exposure to stressors, such as discrimination, victimization/threats, and social
      isolation, could explain these potential disparities and their co-occurrence.
      METHODS: Data come from the cross-sectional Swedish National Public Health
      Survey, which collected random samples of individuals (16-84 years of age)
      annually from 2008 to 2015, with an overall response rate of 49.7% (n = 79,568
      individuals; 1673 self-identified as lesbian, gay, or bisexual). Population-level
      sexual orientation differences in substance use (i.e., alcohol, tobacco, and
      cannabis) and psychological distress were examined. RESULTS: Our findings showed
      significantly elevated prevalence of high-risk alcohol use, cannabis use, and
      daily tobacco smoking, among sexual minorities compared to heterosexuals. These
      substantial disparities in substance use more often co-occurred with
      psychological distress among sexual minorities than among heterosexuals. The
      elevated risk of co-occurring psychological distress and substance use was most
      notable among gay men relative to heterosexual men (adjusted odds ratio [AOR] =
      2.65, CI 1.98, 3.55), and bisexual women relative to heterosexual women (AOR =
      3.01, CI 2.43, 3.72). Multiple mediation analyses showed that experiences of
      discrimination, victimization, and social isolation partially explained the
      sexual orientation disparity in these co-occurring problems. CONCLUSIONS: This
      study adds to a growing body of research showing that sexual minorities
      experience multiple threats to optimal health and points toward future
      interventions that address the shared sources of these overlapping health threats
      in stigma-related stress.

PMID- 29450602
TI  - The onion skin sign of appendiceal mucocele.

PMID- 29450601
TI  - Usefulness of perfusion- and diffusion-weighted imaging to differentiate between
      pilocytic astrocytomas and high-grade gliomas: a multicenter study in Japan.
AB  - PURPOSE: Imaging findings of pilocytic astrocytoma (PA) vary widely, sometimes
      resembling those of high-grade glioma (HGG). This study aimed to identify the
      imaging parameters that can be used to differentiate PA from HGG. METHODS:
      Altogether, 60 patients with PAs and 138 patients with HGGs were included in the
      study. Tumor properties and the presence of hydrocephalus, peritumoral edema, and
      dissemination were evaluated. We also measured the maximum relative cerebral
      blood flow (rCBFmax) and volume (rCBVmax) and determined the minimum apparent
      diffusion coefficient (ADCmin) in the tumor's solid components. The relative T1
      (rT1), T2 (rT2), and contrast-enhanced T1 (rCE-T1) intensity values were
      evaluated. Parameters were compared between PAs and HGGs using the Mann-Whitney U
      test. Receiver operating characteristic (ROC) curve analysis was also used to
      evaluate these imaging parameters. A value of P < .05 was considered to indicate
      significance. RESULTS: Intratumoral hemorrhage and calcification were observed in
      10.0% and 21.7% of PAs, respectively. The rCBFmax and rCBVmax values were
      significantly lower in PAs (0.50 +/- 0.35, 1.82 +/- 1.21) than those in HGGs
      (2.98 +/- 1.80, 9.54 +/- 6.88) (P < .0001, P = .0002, respectively). The ADCmin
      values were significantly higher in PAs (1.36 +/- 0.56 * 10-3 mm2/s) than those
      in HGGs (0.86 +/- 0.37 * 10-3 mm2/s) (P < .0001). ROC analysis showed that the
      best diagnostic performance was achieved with rCBFmax. CONCLUSION: The rCBFmax,
      rCBVmax, and ADCmin can differentiate PAs from HGGs.

PMID- 29450603
TI  - A "wandering spleen".

PMID- 29450604
TI  - The "perinephric cobwebs" sign.

PMID- 29450605
TI  - Abbreviated mpMRI protocol for diffuse liver disease: a practical approach for
      evaluation and follow-up of NAFLD.
AB  - AIM: Multiparametric magnetic resonance imaging (mpMRI) may help determine the
      metabolic profile of patients with obesity and metabolic syndrome in addition to
      their clinical and laboratory biomarkers for diagnosis and monitoring. An
      abbreviated mpMRI protocol may be a faster, less-costly, and easier to perform
      alternative for the diagnosis, treatment, and follow-up of patients with NAFLD
      and for use in clinical trials. OBJECTIVE: To evaluate an abbreviated mpMRI
      protocol tailored to analyze quantitative imaging features of patients with
      obesity and NAFLD and assess its use during treatment. METHODS: This prospective
      study included patients with obesity and NAFLD to perform a quantitative analysis
      of liver fat and iron content, stiffness, as well as the visceral adipose tissue
      (VAT) during the course of a physical exercise-based treatment regimen. RESULTS:
      Longitudinal improvements in imaging features were observed in patients with good
      response to treatment, in accordance with improvements in biochemical and
      anthropometric biomarkers. CONCLUSION: An abbreviated mpMRI protocol consisting
      of liver fat and iron quantification, MR elastography, and VAT measurements is a
      feasible, less-costly, and accessible option for screening and monitoring of
      patients with obesity, NAFLD, and metabolic syndrome.

PMID- 29450606
TI  - Combination transarterial chemoembolization and microwave ablation improves local
      tumor control for 3- to 5-cm hepatocellular carcinoma when compared with
      transarterial chemoembolization alone.
AB  - PURPOSE: To compare transarterial chemoembolization (TACE) monotherapy to
      combination TACE and microwave ablation (MWA) for local control of 3- to 5-cm
      hepatocellular carcinoma (HCC). METHODS: Patients with HCC between 3 and 5 cm
      treated with TACE monotherapy or combination TACE + MWA at a single institution
      between 2007 and 2016 were retrospectively reviewed. Twenty-four HCCs (median
      diameter 3.8 cm) in 16 patients (13 males; median age 64 years) were treated
      using TACE monotherapy. Combination TACE + MWA was used to treat 23 HCCs (median
      diameter 4.2 cm) in 22 patients (18 males; median age 61 years). Microwave
      ablation was performed at a target time of two weeks following TACE. Individual
      tumors were followed by serial contrast-enhanced CT or MR. Response to treatment
      was evaluated on a tumor-by-tumor basis using mRECIST criteria with the primary
      outcome being local tumor progression (LTP). Data were analyzed using Fisher's
      exact test for categorical variables and Wilcoxon rank sum test for continuous
      variables. Time to LTP was estimated with the Kaplan-Meier method. RESULTS:
      Relative to TACE monotherapy, TACE + MWA provided a trend toward both a lower
      rate of LTP (34.8% vs. 62.5%, p = 0.11) and a higher complete response rate
      (65.2% vs. 37.5%; p = 0.12). Time to LTP (22.3 months vs. 4.2 months; p = 0.001)
      was significantly longer in the TACE + MWA group compared to TACE monotherapy.
      CONCLUSIONS: Combination therapy with TACE and microwave ablation improves local
      control and increases time to LTP for 3-5 cm HCC.

PMID- 29450607
TI  - The "caput medusae" sign in portal hypertension.

PMID- 29450608
TI  - Imaging findings of ovarian dysgerminoma with emphasis on multiplicity and
      vascular architecture: pathogenic implications.
AB  - We report the imaging findings of three ovarian dysgerminomas that coexisted with
      other germ cell tumors or gonadoblastomas, focusing on the distribution of tumor
      nests and vascular architecture, which might provide information about the
      pathogenesis of dysgerminomas. In a 14-year-old female with dysgerminoma and
      coexisting gonadoblastomas, contrast-enhanced magnetic resonance imaging (MRI)
      demonstrated a solid mass in the right ovary, which presented as hyperintense
      lobules on diffusion-weighted imaging separated by fibrovascular septa. Some
      small nodules were found to exist separately from the lobules (multiplicity) and
      to include pathological remnants of gonadoblastoma. Large tumor vessels were
      present at the center of the mass (central blood vessels), which were in direct
      contact with the ovarian veins and radiated peripherally through the
      fibrovascular septa. In a 35-year-old female, a mixed germ cell tumor, which was
      mainly composed of dysgerminoma and yolk sac tumor foci, exhibited the same
      vascular architecture pattern as the first dysgerminoma on contrast-enhanced
      computed tomography. In a 10-year-old female with a mixed germ cell tumor,
      contrast-enhanced MRI revealed an enlarged left ovary, which contained a large
      heterogeneous mass and multiple tiny nodules (multiplicity). Microscopically, the
      former corresponded to a yolk sac tumor, and the latter corresponded to a
      dysgerminoma containing remnants of gonadoblastoma. Based on these cases, the
      presence of tumor nest multiplicity and central blood vessels might aid the
      diagnosis of dysgerminoma, and these imaging findings might be indicative of the
      synchronous development of multiple dysgerminomas from primordial germ cells or
      gonadoblastomas.

PMID- 29450593
TI  - Comparison of European ICU patients in 2012 (ICON) versus 2002 (SOAP).
AB  - PURPOSE: To evaluate differences in the characteristics and outcomes of intensive
      care unit (ICU) patients over time. METHODS: We reviewed all epidemiological
      data, including comorbidities, types and severity of organ failure,
      interventions, lengths of stay and outcome, for patients from the Sepsis
      Occurrence in Acutely ill Patients (SOAP) study, an observational study conducted
      in European intensive care units in 2002, and the Intensive Care Over Nations
      (ICON) audit, a survey of intensive care unit patients conducted in 2012.
      RESULTS: We compared the 3147 patients from the SOAP study with the 4852 patients
      from the ICON audit admitted to intensive care units in the same countries as
      those in the SOAP study. The ICON patients were older (62.5 +/- 17.0 vs. 60.6 +/-
      17.4 years) and had higher severity scores than the SOAP patients. The proportion
      of patients with sepsis at any time during the intensive care unit stay was
      slightly higher in the ICON study (31.9 vs. 29.6%, p = 0.03). In multilevel
      analysis, the adjusted odds of ICU mortality were significantly lower for ICON
      patients than for SOAP patients, particularly in patients with sepsis [OR 0.45
      (0.35-0.59), p < 0.001]. CONCLUSIONS: Over the 10-year period between 2002 and
      2012, the proportion of patients with sepsis admitted to European ICUs remained
      relatively stable, but the severity of disease increased. In multilevel analysis,
      the odds of ICU mortality were lower in our 2012 cohort compared to our 2002
      cohort, particularly in patients with sepsis.

PMID- 29450609
TI  - Effect of gantry rotation speed and scan mode on peristalsis motion artifact
      frequency and severity at abdominal CT.
AB  - PURPOSE: The purpose of the study was to understand the effect of CT gantry speed
      and axial vs. helical scan mode on the frequency and severity of bowel
      peristalsis artifacts. METHOD: We retrospectively identified 150 oncologic
      abdominopelvic CT scans obtained on a 256 slice CT scanner: 50 scans obtained
      with Axial mode and 0.5-s gantry rotation time (Slow-Axial); 50 with Axial mode
      and 0.28-s gantry rotation time (Fast-Axial); and 50 scans with Helical mode and
      0.28-s gantry rotation time (Fast-Helical). The patients included 74 women and 76
      men with a mean age of 61 years (range 22-85 years). Two readers viewed all CT
      scans to record the presence and severity of bowel peristalsis artifact, location
      of artifact (stomach, duodenum/jejunum, ileum, and colon) and artifact location
      relative to bowel interface (gas-bowel, fluid-bowel, and gas-fluid). The severity
      of artifacts was recorded subjectively on a 3-point scale, and objectively based
      on maximum length of the artifact. RESULTS: Peristalsis artifact was more
      commonly seen with Slow-Axial scan acquisition (37 of 50 patient scans, or 74%)
      than Fast-Axial (15 in 50 patient scans, or 30%, p < 0.001) and Fast-Helical (22
      of 50 patient scans, or 44%, p < 0.005). The bowel segment distribution and
      severity of peristalsis artifacts were not significantly different between scan
      techniques. CONCLUSION: Peristalsis artifacts are common at abdominopelvic CT
      scans. Fast gantry rotation speed significantly reduces the frequency of bowel
      peristalsis artifacts and should be a consideration when imaging of bowel and
      structures near bowel is critical.

PMID- 29450610
TI  - CTC technique: methods to ensure an optimal exam.
AB  - CT colonography (CTC) has demonstrated equivalent accuracy to optical colonoscopy
      in the detection of clinically relevant polyps and tumors but this is only
      possible when technique is optimized. The two most important features of a high
      quality CTC are a well-prepared colon and a distended colon. This article will
      discuss the dietary, bowel preparation, and fecal/fluid tagging options to best
      prepare the colon. Strategies to optimally distend the colon will also be
      discussed. CT scan techniques including patient positioning and radiation dose
      optimization will be reviewed. With proper technique which includes sufficient
      bowel preparation, fecal/fluid tagging, bowel distension, and optimized scan
      technique, high-quality CTC examinations should become more feasible, easier to
      interpret, and more consistently reproducible leading to increased utilization
      and increased referrals.

PMID- 29450611
TI  - High spatial resolution navigated 3D T1-weighted hepatobiliary MR cholangiography
      using Gd-EOB-DTPA for evaluation of biliary anatomy in living liver donors.
AB  - PURPOSE: To determine the feasibility of high-resolution navigated three
      dimensional (3D) T1-weighted hepatobiliary MR cholangiography (Nav T1 MRC) using
      Gd-EOB-DTPA for biliary visualization in living liver donors and to assess added
      value of 3D T1-weighted hepatobiliary MRCs in improving the confidence and
      diagnostic accuracy of biliary anatomy in complementary to T2-weighted MRCs.
      METHODS: Twenty-nine right liver donors underwent 3D T2 MRC, 2D T2 MRC, breath
      hold T1-weighted hepatobiliary MRC (BH T1 MRC), and Nav T1 MRC. Two readers
      independently reviewed and compared 3D/2D MRC set, added BH T1 MRC set, and added
      Nav T1 MRC set for biliary diagnostic accuracy and confidence. For each MRC,
      biliary segments visualization and image quality were scored. RESULTS: Both BH T1
      MRC and Nav T1 MRC improved accuracy and specificity in biliary diagnosis when
      added to 3D/2D T2 MRC-alone set, though without statistical significance (R1,
      82.8% to 93.1%; R2, 82.8% to 89.7%). The added Nav T1 MRC set showed the highest
      diagnostic confidence with both readers. Both readers scored Nav T1 MRC with the
      highest visualization scores for branching ducts and overall ducts. CONCLUSION:
      Combining T1-weighted hepatobiliary MRCs to 3D/2D T2 MRC set improved accuracy
      for biliary anatomy diagnosis; time-efficient BH T1 MRC in axial and coronal
      planes should be considered as a key MRC sequence complementary to T2 MRCs. Given
      excellent biliary visualization and superior diagnostic confidence, Nav T1 MRC in
      selected subjects with breath-hold difficulties and inconclusive or complex
      biliary variations may assist in reaching a correct biliary diagnosis.

PMID- 29450612
TI  - The "serpent sign" in hydatid disease.

PMID- 29450613
TI  - Extracolonic findings and radiation at CT colonography: what the referring
      provider needs to know.
AB  - A better understanding of the risks and benefits of extracolonic findings and
      radiation dose will aid in the safe and proper implementation of CT colonography
      in clinical practice. The majority of extracolonic findings in screening patients
      are benign and can be ignored by referring physicians. Radiologists also need to
      be responsible in reporting extracolonic findings. Referring providers must be
      knowledgeable about the theoretic risks and controversies regarding the use of
      ionizing radiation. Screening CT colonography imparts a low-level of radiation to
      patients that is equivalent or less than annual background dose.

PMID- 29450614
TI  - White liver sign.

PMID- 29450615
TI  - Contrast-enhanced ultrasound (CEUS) in abdominal intervention.
AB  - The introduction of ultrasound contrast agents has rendered contrast-enhanced
      ultrasound (CEUS) a valuable complementary technique to address clinically
      significant problems. This pictorial review describes the use of CEUS guidance in
      abdominal intervention and illustrates such application for a range of clinical
      indications. Clinical application of CEUS discussed include commonly performed
      abdominal interventional procedures, such as biopsy, drainage, nephrostomy,
      biliary intervention, abdominal tumor ablation and its subsequent monitoring, and
      imaging of vascular complications following abdominal intervention. The purpose
      of this article is to further familiarize readers with the application of CEUS,
      particularly its specific strength over alternative imaging modalities, in
      abdominal intervention.

PMID- 29450616
TI  - Early motor signs of autism spectrum disorder in spontaneous position and
      movement of the head.
AB  - We examined the characteristics of spontaneous movements at 9-20 weeks postterm
      age in very low birth-weight infants who later developed autism spectrum disorder
      (ASD). We analyzed video recordings of spontaneous movements of 39 children who
      had no clinical issues [typically developing (TD) group], 21 children who showed
      developmental delay, and 14 children who were diagnosed with ASD (ASD group) at 6
      years of age. Head position in each video frame was classified by visual
      inspection. The percentage of midline head position (PMHP) and number of changes
      in head position were calculated. Spontaneous limb movements were quantified
      using six indices. The values of PMHP were significantly lower in the ASD group
      than in the TD group. The lower PMHP during early infancy is associated with
      later development of ASD. Poorer performance in maintaining midline position of
      the head at this period may distinguish infants who later develop ASD from those
      who show TD.

PMID- 29450617
TI  - A natural variant of arylsulfatase from Kluyveromyces lactis shows no
      formylglycine modification and has no enzyme activity.
AB  - Kluyveromyces lactis is a common fungal microorganism used for the production of
      enzyme preparations such as beta-galactosidases (native) or chymosin
      (recombinant). It is generally important that enzyme preparations have no
      unwanted side activities. In the case of beta-galactosidase preparations produced
      from K. lactis, an unwanted side activity could be the presence of arylsulfatase
      (EC 3.1.6.1). Due to the action of arylsulfatase, an unpleasant "cowshed-like"
      off-flavor would occur in the final product. The best choice to avoid this is to
      use a yeast strain without this activity. Interestingly, we found that certain
      natural K. lactis strains express arylsulfatases, which only differ in one amino
      acid at position 139. The result of this difference is that K. lactis DSM 70799
      (expressing R139 variant) shows no arylsulfatase activity, unlike K. lactis GG799
      (expressing S139 variant). After recombinant production of both variants in
      Escherichia coli, the R139 variant remains inactive, whereas the S139 variant
      showed full activity. Mass spectrometric analyses showed that the important
      posttranslational modification of C56 to formylglycine was not found in the R139
      variant. By contrast, the C56 residue of the S139 variant was modified. We
      further investigated the packing and secondary structure of the arylsulfatase
      variants using optical spectroscopy, including fluorescence and circular
      dichroism. We found out that the inactive R139 variant exhibits a different
      structure regarding folding and packing compared to the active S139 variant. The
      importance of the amino acid residue 139 was documented further by the
      construction of 18 more variants, whereof only ten showed activity but always
      reduced compared to the native S139 variant.

PMID- 29450618
TI  - Influence of membrane fatty acid composition and fluidity on airborne survival of
      Escherichia coli.
AB  - Finding ways to predict and control the survival of bacterial aerosols can
      contribute to the development of ways to alleviate a number of crucial
      microbiological problems. Significant damage in the membrane integrity of
      Escherichia coli during aerosolization and airborne suspension has been revealed
      which has prompted the question of how the membrane fatty acid composition and
      fluidity influence the survival of airborne bacteria. Two approaches of using
      isogenic mutants and different growth temperatures were selected to manipulate
      the membrane fatty acid composition of E. coli before challenging the bacteria
      with different relative humidity (RH) levels in an aerosol chamber. Among the
      mutants (fabR - , cfa. fadA - ), fabR - had the lowest membrane fluidity index
      (FI) and generally showed a higher survival than the parental strain.
      Surprisingly, its resistance to airborne stress was so strong that its viability
      was fully maintained even after airborne suspension at 40% RH, a harsh RH level
      to bacterial survival. Moreover, E. coli cultured at 20  degrees C with a higher
      FI than that at 30 and 37  degrees C generally had a lower survival after
      aerosolization and airborne suspension. Unlike FI, individual fatty acid and
      cyclopropane fatty acid composition did not relate to the bacterial survival.
      Lipid peroxidation of the membrane was undetected in all the bacteria. Membrane
      fluidity plays a stronger role in determining the bacteria survival during
      airborne suspension than during aerosolization. Certain relationships between FI
      and bacteria survival were identified, which could help predict the transmission
      of bacteria under different conditions.

PMID- 29450620
TI  - Targeting the neddylation pathway in cells as a potential therapeutic approach
      for diseases.
AB  - The ubiquitin-proteasome system (UPS) is an important system that regulates the
      balance of intracellular proteins, and it is involved in the regulation of
      multiple vital biological processes. The approval of bortezomib for relapsed and
      refractory multiple myeloma has proven that agents targeting the UPS have the
      potential to be effective treatment strategies for diseases. Among of all of the
      components of the UPS, cullin-RING ligases (CRLs) are the focus of research. CRLs
      are the largest family of ubiquitin E3 ligases and they play a critical role in
      substrate binding. CRL activity is modulated by many pathways in which
      neddylation modification is the essential process for cullin activation. Thus,
      targeting the neddylation pathway of cullins could indirectly affect CRL
      activity, thereby interfering with substrate protein ubiquitination. In addition
      to cullin proteins, there are some other target proteins of neddylation, such as
      p53, mouse double minute 2, and epidermal growth factor receptor. For target
      proteins, neddylation modification mainly causes functions changes, not
      degradation. In addition, the level of neddylation is also closely related to
      disease development and prognosis. In this review, we summarize the research on
      some target proteins and active target agents of neddylation pathways, and
      explore the role of neddylation in disease therapy. We came to the conclusion
      that conducting research on neddylation may be a potential approach to discover
      some novel targets and agents that could be effective without serious side
      effects.

PMID- 29450619
TI  - Immediate response mechanisms of Gram-negative solvent-tolerant bacteria to cope
      with environmental stress: cis-trans isomerization of unsaturated fatty acids and
      outer membrane vesicle secretion.
AB  - Bacteria have evolved an array of adaptive mechanisms enabling them to survive
      and grow in the presence of different environmental stresses. These mechanisms
      include either modifications of the membrane or changes in the overall energy
      status, cell morphology, and cell surface properties. Long-term adaptations are
      dependent on transcriptional regulation, the induction of anabolic pathways, and
      cell growth. However, to survive sudden environmental changes, bacterial short
      term responses are essential to keep the cells alive after the occurrence of an
      environmental stress factor such as heat shock or the presence of toxic organic
      solvents. Thus far, two main short-term responses are known. On the one hand, a
      fast isomerization of cis into trans unsaturated fatty leads to a quick
      rigidification of the cell membrane, a mechanism known in some genera of Gram
      negative bacteria. On the other hand, a fast, effective, and ubiquitously present
      countermeasure is the release of outer membrane vesicles (OMVs) from the cell
      surface leading to a rapid increase in cell surface hydrophobicity and finally to
      the formation of cell aggregates and biofilms. These immediate response
      mechanisms just allow the bacteria to stay physiologically active and to employ
      long-term responses to assure viability upon changing environmental conditions.
      Here, we provide insight into the two aforementioned rapid adaptive mechanisms
      affecting ultimately the cell envelope of Gram-negative bacteria.

PMID- 29450621
TI  - NGF protects corneal, retinal, and cutaneous tissues/cells from phototoxic effect
      of UV exposure.
AB  - PURPOSE: Based on evidence that nerve growth factor (NGF) exerts healing action
      on damaged corneal, retinal, and cutaneous tissues, the present study sought to
      assess whether topical NGF application can prevent and/or protect epithelial
      cells from deleterious effects of ultraviolet (UV) radiation. METHODS: Eyes from
      40 young-adult Sprague Dawley rats and cutaneous tissues from 36 adult nude mice
      were exposed to UVA/B lamp for 60 min, either alone or in the presence of murine
      NGF. Corneal, retinal, and cutaneous tissues were sampled/processed for
      morphological, immunohistochemical, and biomolecular analysis, and results were
      compared statistically. RESULTS: UV exposure affected both biochemical and
      molecular expression of NGF and trkANGFR in corneal, retinal, and cutaneous
      tissues while UV exposure coupled to NGF treatment enhanced NGF and trkANGFR
      expression as well as reduced cell death. CONCLUSIONS: Overall, the findings of
      this in vivo/ex vivo study show the NGF ability to reduce the potential UV
      damage. Although the mechanism underneath this effect needs further
      investigation, these observations prospect the development of a pharmacological
      NGF-based therapy devoted to maintain cell function when exposed to phototoxic UV
      radiation.

PMID- 29450623
TI  - [Statement of the BVA and DOG on eye examinations in patients with high visual
      defects : Status January 2018].

PMID- 29450624
TI  - [Intraoperative optical coherence tomography in explorative vitrectomy in
      patients with vitreous haemorrhage-a case series].
AB  - BACKGROUND: High-resolution spectral domain optical coherence tomography (SD-OCT)
      is a gold standard technique for diagnosis, management and monitoring of patients
      with vitreoretinal diseases. Preoperative diagnostics for evaluation of
      intraocular and retinal status in patients with vitreous haemorrhage are limited,
      thus final therapeutic decisions can only be made during explorative vitrectomy.
      We evaluated the use of intraoperative SD-OCT (iSD-OCT) as a real-time additional
      diagnostic tool during explorative vitrectomy in patients with vitreous
      haemorrhage. METHODS: We report on 9 patients (11 eyes) with vitreous
      haemorrhage. Preoperative ultrasound was performed to evaluate intraocular
      status. Subsequently, an explorative 23G pars plana vitrectomy was performed
      under visualisation with the OPMI Lumera 700 surgical microscope (Carl Zeiss
      Meditec, Jena, Germany) equipped with a fully integrated iSD-OCT device (Rescan
      700, Carl Zeiss Meditec, Jena, Germany) as a real-time diagnostic tool. RESULTS:
      In all patients, intraoperative iSD-OCT allowed real-time evaluation of the
      preretinal, intraretinal and subretinal structures in addition to the
      intraoperative en face image. The further surgical strategy, i. e. necessity for
      peeling of epiretinal membranes (ERM) or of the inner limiting membrane (ILM),
      application of intravitreal medication and selection of the appropriate
      tamponade, was based on and optimised according to the iSD-OCT images.
      CONCLUSION: Intraoperative iSD-OCT is highly useful as an additional
      intraoperative diagnostic tool in patients with vitreous haemorrhage. In addition
      to the en face microscope image, it facilitates intraoperative real-time
      diagnosis and aids therapeutic decision-making during surgery.

PMID- 29450622
TI  - Comparison of retinal microvascular changes in eyes with high-tension glaucoma or
      normal-tension glaucoma: a quantitative optic coherence tomography angiographic
      study.
AB  - PURPOSE: The aim of this study is to determine and compare the changes in the
      retinal vasculature in eyes with high-tension glaucoma (HTG) or normal-tension
      glaucoma (NTG). METHODS: The right eyes of 43 HTG subjects, 33 NTG subjects, and
      51 age- and sex-matched normal subjects were included in this cross-sectional
      study. Signals were projected from the internal limiting membrane to retinal
      pigment epithelium. The retinal perfused vessel densities in the peripapillary
      and parafoveal regions were measured automatically with optic coherence
      tomography angiography and the split-spectrum amplitude-decorrelation angiography
      algorithm. RESULTS: Compared with normal eyes, glaucomatous eyes had a smaller
      retinal nerve fibre layer (RNFL) thickness, smaller full parafoveal retinal
      thickness, and lower retinal perfused vessel density (PVD) in the peripapillary
      and parafoveal regions (all P < 0.01). The visual field, RNFL and retinal
      thicknesses, and PVD in the parafoveal region in the HTG eyes were similar to
      those in the NTG eyes. However, the NTG eyes had a significantly lower mean PVD
      than the HTG eyes in the peripapillary region. When the different sectors of the
      peripapillary region were studied, the difference was still significant in most
      sectors (all P < 0.05), except the inferotemporal sector (P = 0.676).
      CONCLUSIONS: The retinal perfused vessel density is significantly reduced in HTG
      and NTG eyes, and more prominently in the peripapillary region in NTG eyes.

PMID- 29450625
TI  - Mechanical Thrombectomy in Patients with Acute Ischemic Stroke on Anticoagulation
      Therapy.
AB  - INTRODUCTION/PURPOSE: Mechanical thrombectomy (MT) for acute ischemic stroke (IS)
      can be performed also in patients on anticoagulation therapy (AT); however,
      sufficient and reliable data about safety and efficacy of MT are still missing.
      Thus, we aimed to compare these parameters between patients treated on AT and
      without AT. MATERIALS AND METHODS: All consecutive IS patients treated with MT
      using stent retrievers were included in the retrospective analysis. Neurological
      deficit was scored using National Institutes of Health Stroke Scale (NIHSS) and
      90-day clinical outcome using modified Rankin scale with a score 0-2 for good
      outcome. Recanalization was rated using Thrombolysis in Cerebral Infarction
      (TICI) scale. Symptomatic intracerebral hemorrhage (SICH) was assessed according
      to the SITS-MOST criteria. RESULTS: Out of 703 patients treated with MT, 88
      (12.5%) patients (46% males, mean age 75.5 +/- 11.8 years) were on AT with an
      admission median NIHSS of 17 points. Recanalization (TICI 2b-3) was achieved in
      80% and complete (TICI 3) in 65% of patients on AT and in 80 and 65% of patients
      without AT (p-1.000). SICH after MT was detected in 9% of AT and 5% of non-AT
      patients (p-0.136). Good outcome was present in 36% of AT patients (p-0.03). AT
      patients with poor outcome had more frequently atrial fibrillation (93%, p
      0.005), higher admission NIHSS (17, p-0.004) and higher rate of SICH (14.5%, p
      0.047). CONCLUSION: MT seems to be safe also in patients on AT. Poor outcome may
      be related to higher admission NIHSS, higher rate of SICH and presence of atrial
      fibrillation.

PMID- 29450626
TI  - In a Spin: A Novel Method for Inferior Vena Cava (IVC) Filter Detachment
      Following Snare Entanglement.

PMID- 29450627
TI  - Can the use of a single integrated unitary autonomic index provide early clues
      for eventual eligibility for olympic games?
AB  - PURPOSE: Optimal autonomic regulation and stress resilience might be considered
      critical elements of athletic performance. We hypothesize that a novel unitary
      autonomic index for sports (ANSIs), together with a somatic stress related
      symptom score (4SQ) might help characterize athletes who were eventually selected
      for the Rio 2016 Olympic Games Italian team (Rio +). METHODS: In this
      retrospective study we examined 778 athletes (age 24.4 +/- 6.7 yrs) who underwent
      a planned yearly pre-participation screening. All athletes underwent clinical,
      autonomic and exercise ECG evaluation. The combination of vagal and sympathetic
      indices from RR variability into ANSIs was performed by radar plot and percent
      ranking of index variables. We assessed (Rio +) versus (Rio -) athletes also
      after subdivision into three sport intensity groups (low, mid and high
      intensity). RESULTS: Overall there were no significant differences between (Rio
      +) and (Rio -) athletes when considering individual spectral derived variables.
      Conversely, the unitary Index ANSIs was significantly higher in (Rio +) compared
      to (Rio -) athletes (respectively 54.5 +/- 29.5 and 47.9 +/- 28.4 p = 0.014).
      This difference was particularly evident (p = 0.017) in the group of athletes
      characterized by both high static and dynamic components. 4SQ was smaller in the
      (Rio +) group, particularly in the groups of athletes characterized by both low
      medium static and dynamic components. CONCLUSIONS: ANSIs, a proxy of integrated
      cardiac autonomic regulation and simple assessment of resilience to stress, may
      differentiate Italian athletes who were eventually selected for participation in
      the 2016 Rio Olympic Games from those who were not, suggesting the possibility of
      a "winning functional phenotype".

PMID- 29450628
TI  - Relation between lactic acid and base excess during muscular exercise.

PMID- 29450629
TI  - Congenital cervical kyphosis in an infant with Ehlers-Danlos syndrome.
AB  - BACKGROUND: Ehler-Danlos syndome (EDS) refers to a group of heritable connective
      tissue disorders; rare manifestations of which are cervical kyphosis and clinical
      myelopathy. Surgical treatment is described for the deformity in the
      thoracolumbar spine in adolescents but not for infantile cervical spine. Internal
      fixation for deformity correction in the infantile cervical spine is challenging
      due to the diminutive size of the bony anatomy and the lack of spinal
      instrumentation specifically designed for young children. We describe the first
      case of successful surgical treatment in an infant with a high cervical kyphotic
      deformity in EDS. CASE PRESENTATION: A 15-month-old female with EDS presented
      with several months of regression in gross motor skills in all four extremities.
      Imaging demonstrated 45 degrees  of kyphosis from the C2-4 levels with spinal
      cord compression. Corrective surgery consisted of a C3 corpectomy and C2-4
      anterior fusion with allograft block and anterior fixation with dual 2 * 2 hole
      craniofacial miniplates, supplemented by C2-4 posterior fusion using four
      craniofacial miniplates fixated to the lamina. Radiographs at 20 months post
      surgery demonstrated solid fusion both anteriorly and posteriorly with
      maintenance of correction. CONCLUSIONS: Ehlers-Danlos syndrome may present in the
      pediatric population with congenital kyphosis from cervical deformity in addition
      to the more commonly seen thoracolumbar deformities.

PMID- 29450630
TI  - Outermost layer-oriented medial approach for infrapyloric nodal dissection in
      laparoscopic distal gastrectomy.
AB  - BACKGROUND: Based on our experience of suprapancreatic nodal dissection in
      laparoscopic gastrectomy, we developed an outermost layer-oriented medial
      approach for infrapyloric nodal dissection. The objective of this single
      institution retrospective study was to determine the feasibility, safety, and
      reproducibility of this novel and unique dissection procedure. METHODS: This
      approach can be performed in the same manner as suprapancreatic nodal dissection
      but by replacing the left gastric artery with the right gastroepiploic artery
      (RGEA), the common hepatic artery with the anterior superior pancreaticoduodenal
      artery (ASPDA), and the splenic artery with the gastroduodenal artery. It
      comprises five steps: (1) mobilization of the transverse mesocolon along the
      prepancreatic membrane, (2) medial dissection along the dissectable layer between
      the pancreatic head and the dorsal side of the right gastroepiploic vein (RGEV),
      (3) division of the RGEV and determination of the lateral and cranial borders,
      (4) dissection along the outermost layer of the RGEA and ASPDA and transection of
      the infrapyloric artery and RGEA, and (5) transection of the duodenal bulb.
      RESULTS: This novel method was applied in 112 patients who underwent laparoscopic
      distal gastrectomy from 2014 to 2015. The anatomical landmarks that we determined
      to appropriately identify the outermost layer were highly reproducible, and our
      novel procedure based on these landmarks was successfully completed in all cases,
      without any intraoperative complications. Furthermore, in all cases, no. 6 lymph
      nodes were fully and adequately dissected within the infrapyloric area
      anatomically defined in the Japanese Classification of Gastric Carcinoma ver. 14.
      Pancreatic fistula occurred only in 1.8% cases. CONCLUSIONS: This novel outermost
      layer-oriented medial approach is a robust procedure that may help laparoscopic
      surgeons in performing safe and reproducible infrapyloric nodal dissection.

PMID- 29450631
TI  - Preoperative combination of progressive pneumoperitoneum and botulinum toxin type
      A in patients with loss of domain hernia.
AB  - INTRODUCTION: Preoperative progressive pneumoperitoneum (PPP) and botulinum toxin
      type A (BT) are tools in the surgical preparation of patients with loss of domain
      hernias (LODH). The aim of this paper is to report our experience with these
      preoperative techniques in 70 patients with LODH. METHODS: Observational study of
      70 consecutive patients with LODH was conducted between May 2010 and May 2016.
      Diameters of the hernia sac, incisional hernia (VIH), and abdominal cavity (VAC)
      volumes, and VIH/VAC ratio were measured before and after PPP and BT, using
      abdominal CT scan data. Combination of both techniques was performed when the
      VIH/VAC ratio was > 20%. RESULTS: Median insufflated volume of air for PPP was
      8450 +/- 3400 cc (4500-13,450), over a period of 11.3 +/- 2.3 days (9-16). BT
      administration time was 38.1 +/- 3.7 days (35-44). An average reduction of 16.6%
      of the VIH/VAC ratio after PPP and BT was obtained (p < 0.05). Complications
      associated with PPP were 20%, and with surgical technique 29.6%. No complications
      occurred during the BT administration. Reconstructive technique was anterior CST
      in 54 patients, TAR in 14 cases and Rives-Stoppa technique in two patients.
      Median follow-up was 34.5 +/- 22.3 months (12-60) and four cases of hernia
      recurrence (5.7%) were reported. CONCLUSIONS: Using a CT volumetric protocol,
      combination of PPP and BT decreases the VIH/VAC ratio and hernia defect
      diameters, which constitutes a key factor in the treatment of LODH.

PMID- 29450632
TI  - Author Correction: Exploratory analyses assessing the impact of early tumour
      shrinkage and depth of response on survival outcomes in patients with RAS wild
      type metastatic colorectal cancer receiving treatment in three randomised
      panitumumab trials.
AB  - The authors would like to include the following changes in the published article.

PMID- 29450633
TI  - MID1-PP2A complex functions as new insights in human lung adenocarcinoma.
AB  - PURPOSE: MID1 is an E3 ubiquitin ligase that was first found in Opitz G/BBB
      syndrome, but there has been little research into its role in lung diseases. We
      have found an accumulating evidence that indicates the MID1-PP2A complex plays a
      role in asthma and contributes to inflammation, but its roles in lung
      adenocarcinoma are unclear. This study aimed at evaluating the function of MID1
      PP2A complex in human lung adenocarcinoma. METHODS: We used western blot, ELISA
      and real-time quantitative PCR to detect the protein and mRNA levels of MID1 and
      PP2A in A549, H1975, and H1650 lung adenocarcinoma cell lines compared with the
      human bronchial epithelial cell line BEAS-2B. Additionally, we used IHC, ELISA
      and real-time quantitative PCR to dectect MID1 and PP2A levels in 30-paired lung
      adenocarcinoma tissues. We also detected apoptosis, proliferation and cell cycle
      related protein expression after silencing MID1 and activing PP2A. RESULTS: Our
      data show that MID1 was significantly upregulated in 30-paired lung
      adenocarcinoma tissues, and in A549, H1975 and H1650 cell lines compared with
      BEAS-2B. PP2A showed the opposite results. Furthermore, both upregulated MID1 and
      downregulated PP2A were correlated with age, but not sex, TNM stage or smoking
      history. In vitro experiments showed that PP2A was upregulated in lung
      adenocarcinoma cell lines that were transfected with MID1-siRNA, suggesting MID1
      negatively regulates PP2A in lung adenocarcinoma. We also found that silencing
      MID1 expression or activating PP2A induced apoptosis, proliferation and cell
      cycle arrest. CONCLUSIONS: We demonstrated that the MID1-PP2A complex plays an
      important role in lung adenocarcinoma, influencing cell cycle progression,
      proliferation and apoptosis. Our findings showed a novel molecular mechanism of
      lung tumorigenesis that may provide new insights for anti-tumor therapies.

PMID- 29450634
TI  - Prevalence, genotypes, and risk factors of Enterocytozoon bieneusi in Asiatic
      black bear (Ursus thibetanus) in Yunnan Province, Southwestern China.
AB  - Microsporidiosis is an important zoonotic disease, even leading to severe
      diarrhea. However, no information about prevalence and genotypes of
      Enterocytozoon bieneusi infection in Asiatic black bears in southwestern China is
      available. The objectives of the present study were to investigate the prevalence
      of E. bieneusi and to characterize their genotypes using the nested PCR
      amplification of the internal transcribed spacer region of the ribosomal RNA gene
      cluster and multilocus sequence typing (MLST). The overall prevalence of E.
      bieneusi was 19.75% (80/405) and the rate of E. bieneusi in Xishuangbanna
      (33.33%) was significantly higher than that in any other regions (Honghe, 17.65%;
      Dehong, 13.04%; Kunming, 0; P = 0.01). Sequence analysis revealed that 4 known
      genotypes (D, n = 2; SC02, n = 10; SC01, n = 5; and CHB1, n = 4) and 13 novel
      genotypes (designed MJ1-MJ13) were identified. When 17, 5, 14, and 34 sequences
      at loci MS1, MS3, MS4, and MS7 via MLST analyses, representing 4, 4, 5, and 10
      genotypes, respectively, were completed, one multilocus genotype (MLG novel-ABB1)
      was identified. This is the first report of E. bieneusi in Asiatic black bear in
      Yunnan province, Southwestern China. The results indicated the potential zoonotic
      risk of this parasite through the Asiatic black bear in this region and provided
      foundation data for preventing and controlling E. bieneusi infection of many
      other animals and humans in these regions.

PMID- 29450635
TI  - Screening in spouses of colorectal cancer patients: a missed opportunity.
AB  - BACKGROUND: Spouses of colorectal cancer (CRC) patients could be at increased
      risk of developing CRC due to shared lifestyle habits with the patients which is
      a notable risk factor. This study explores the various issues surrounding CRC
      screening among these spouses. METHODS: A mixed method study comprising in-depth
      qualitative semi-structured interviews followed by structured quantitative
      questionnaire was administered to spouses who accompanied CRC patients during
      their appointments, from January 2016 to February 2017. RESULTS: Fifty spouses of
      CRC patients, median age of 60 (range, 41-82) years, were qualitatively
      interviewed but 5 of them did not complete the questionnaire. Only 26 (57.8%) of
      them were current with CRC screening. Data saturation was reached at the 48th
      participant. Four main themes emerged from the qualitative interviews. These
      included (i) adequacy of knowledge and attitudes about CRC screening, (ii)
      suboptimal public health promotion efforts of CRC screening, (iii) barriers of
      CRC screening, and (iv) need for mutual spousal support. From the questionnaires,
      spouses who were not current with CRC screening were more likely to report more
      barriers and have different cues to actions than those who are current. The
      majority of the spouses demonstrated high levels of knowledge on CRC, understood
      its severity and their susceptibility. CONCLUSION: Spouses exhibit high levels of
      knowledge and awareness of the implications of CRC. Apart from addressing
      psychological issues during the acute phases, targeted interventions should be
      considered to improve their screening rates and to use them as advocates for CRC
      screening among family and community.

PMID- 29450636
TI  - Comparing the efficacy of low-dose vs high-dose cyclophosphamide regimen as
      induction therapy in the treatment of proliferative lupus nephritis: a single
      center study.
AB  - : Cyclophosphamide (CYC) has been the backbone immunosuppressive drug to achieve
      sustained remission in lupus nephritis (LN). The aim was to evaluate the efficacy
      and compare adverse effects of low and high dose intravenous CYC therapy in
      Indian patients with proliferative lupus nephritis. An open-label, parallel
      group, randomized controlled trial involving 75 patients with class III/IV LN was
      conducted after obtaining informed consent. The low dose group (n = 38) received
      6 * 500 mg CYC fortnightly and high dose group (n = 37) received 6 * 750 mg/m2
      CYC four-weekly followed by azathioprine. The primary outcome was
      complete/partial/no response at 52 weeks. The secondary outcomes were renal and
      non-renal flares and adverse events. Intention-to-treat analyses were performed.
      At 52 weeks, 27 (73%) in high dose group achieved complete/partial response
      (CR/PR) vs 19 (50%) in low dose (p = 0.04). CR was higher in the high dose vs low
      dose [24 (65%) vs 17 (44%)], although not statistically significant. Non
      responders (NR) in the high dose group were also significantly lower 10 (27%) vs
      low dose 19 (50%) (p = 0.04). The change in the SLEDAI (Median, IQR) was also
      higher in the high dose 16 (7-20) in contrast to the low dose 10 (5.5-14) (p =
      0.04). There was significant alopecia and CYC-induced leucopenia in high dose
      group. Renal relapses were significantly higher in the low dose group vs high
      dose [9 (24%) vs 1(3%), (p = 0.01)]. At 52 weeks, high dose CYC was more
      effective in inducing remission with decreased renal relapses in our population.
      TRIAL REGISTRATION: The study was registered at http://www.clintrials.gov .
      NCT02645565.

PMID- 29450639
TI  - The XLII Spanish Congress of Pediatric Nephrology : 18-20 May 2017, Madrid,
      Spain.

PMID- 29450638
TI  - Religious coping and death depression in Iranian patients with cancer:
      relationships to disease stage.
AB  - PURPOSE: The study investigated relationships among the extent of disease,
      religious coping, and death depression in Iranian patients with cancer. METHOD: A
      descriptive cross-sectional study was conducted with a convenience sample of 482
      Iranian cancer patients. Participants completed demographic and health, death
      depression, and religious coping surveys. RESULTS: After controlling for
      demographic and health characteristics, positive and negative religious coping
      behaviors were significantly related to the experience of death depression. There
      was an interaction effect between negative religious coping and extent of disease
      with significant positive relationships to the experience of death depression.
      CONCLUSIONS: Negative religious coping was found to be more closely associated
      with death depression in patients with earlier stage disease than those with
      advanced stages of cancer in this sample of patients with cancer from Iran.
      Findings support assessing patients for use of religious coping strategies.
      Muslim patients who are religiously alienated and have existential anguish may be
      vulnerable and need heightened support following diagnosis and during treatment
      of early stage cancer.

PMID- 29450637
TI  - Canakinumab treatment in children with familial Mediterranean fever: report from
      a single center.
AB  - Familial Mediterranean fever (FMF), the most common hereditary autoinflammatory
      disorder is characterized by recurrent episodes of fever, serositis, arthritis.
      The major long-term result is amyloidosis. Colchicine remains the principle of
      the treatment; it not only prevents the acute attacks but also prevents the long
      term complications such as amyloidosis; 5-10% of the patients are unresponsive to
      treatment. Recently new therapeutic options as anti-interleukin 1 agents are
      successfully used for the patients who do not respond to colchicine treatment. In
      this study, we retrospectively evaluated 11 pediatric colchicine-resistant FMF
      patients who were treated with canakinumab. Three of the patients had amyloidosis
      and two had uveitis. Based on our results, we suggest that canakinumab may be a
      safe and effective therapy in patients who are resistant to colchicine and even
      in the patients with amyloidosis. We also suggest that canakinumab might be a
      safe option for the patients with uveitis.

PMID- 29450640
TI  - Incidence of perioperative complications in total hip and knee arthroplasty in
      patients with Parkinson disease.
AB  - INTRODUCTION: The aim of this study is to evaluate the difference in
      perioperative complication rate in total hip, bipolar hemiarthroplasties and
      total knee arthroplasty in patients with Parkinson disease in trauma and elective
      surgery in our Musculoskeletal Center during a period of 10 years. MATERIAL AND
      METHOD: Between 2006 and 2016, 45 bipolar hemiarthroplasties in trauma surgery,
      15 total knee and 19 total hip arthroplasties in patients with Parkinson's
      disease were performed. We divided the patients in two groups. Group I included
      trauma cases (45) and group II elective surgery cases (34). Complications were
      documented and divided into local minor and major complications and general minor
      and major complications. Fisher's exact test was used for statistical evaluation.
      RESULTS: In both groups, there was one local major complication (p > 0.05): In
      group I, there was one case of loosening of a K-wire which was removed
      operatively. In group II, there was one severe intraarticular bleeding requiring
      puncture of the hematoma. In group I, there were 38 general complications; in
      group II, there were 17 general complications. There was no statistical
      difference in complication rate (p > 0.05). CONCLUSION: Total hip arthroplasty,
      bipolar hemiarthroplasties and knee arthroplasty in patients with Parkinson
      disease is possible in elective and trauma surgery. Complication rate is higher
      in comparison with patients not suffering from Parkinson disease, but there is no
      difference in complication rate in elective and trauma surgery. Nevertheless,
      early perioperative neurological consultation in patients with Parkinson disease
      is recommended to minimize complications and improve early outcomes after
      arthroplasty.

PMID- 29450641
TI  - Chronic lymphocytic leukemia cells acquire regulatory B-cell properties in
      response to TLR9 and CD40 activation.
AB  - Circulating chronic lymphocytic leukemia (CLL) cells share phenotypic features
      with certain subsets of regulatory B-cells (Bregs). The latter cells have been
      reported to negatively regulate immune cell responses, mostly by provision of IL
      10. The purpose of the current study was to identify and delineate Breg
      properties of CLL cells. B-cells and T-cells were obtained from the peripheral
      blood of untreated CLL patients diagnosed according to the 2008 Guidelines of the
      International Workshop on Chronic Lymphocytic Leukemia. Co-culture assays were
      used to examine the ability of CLL cells to suppress autologous T-cell immune
      responses. IL-10 potency of CLL cells was assessed following stimulation with
      activators of the toll-like receptor 9 (TLR9) or CD40 and was correlated with the
      inhibitory activity of the cells. TLR9-activated CLL cells were found to increase
      the frequency of CD4+CD25hiFOXp3+ regulatory T-cells (Tregs) and to inhibit
      autologous CD4+ T-cell proliferation. This signaling cascade proved to control IL
      10 generation in CLL cells, which in turn promoted the inhibition of T-cell
      proliferation by CLL cells. However, CD40 activation of CLL cells, while
      exhibiting a similar ability to augment Treg frequency, did not either affect IL
      10 generation or T-cell proliferation. In conclusion, CLL cells demonstrate a
      unique clonal quality of adopting Breg properties which promote modulation of T
      cell characteristics. TLR9 appears to be a potent activator of regulatory
      abilities in CLL cells, possibly contributing to preferential immune escape of
      TLR9-responsive cells.

PMID- 29450642
TI  - Risk factors of non-specific spinal pain in childhood.
AB  - PURPOSE: Non-specific spinal pain can occur at all ages and current evidence
      suggests that pediatric non-specific spinal pain is predictive for adult spinal
      conditions. A 5-year long, prospective cohort study was conducted to identify the
      lifestyle and environmental factors leading to non-specific spinal pain in
      childhood. MATERIALS AND METHODS: Data were collected from school children aged 7
      16 years, who were randomly selected from three different geographic regions in
      Hungary. The risk factors were measured with a newly developed patient-reported
      questionnaire (PRQ). The quality of the instrument was assessed by the
      reliability with the test-retest method. Test (N = 952) and validity (N = 897)
      datasets were randomly formed. Risk factors were identified with uni- and
      multivariate logistic regression models and the predictive performance of the
      final model was evaluated using the receiver operating characteristic (ROC)
      method. RESULTS: The final model was built up by seven risk factors for spinal
      pain for days; age > 12 years, learning or watching TV for more than 2 h/day,
      uncomfortable school-desk, sleeping problems, general discomfort and positive
      familiar medical history (chi2 = 101.07; df = 8; p < 0.001). The probabilistic
      performance was confirmed with ROC analysis on the test and validation cohorts
      (AUC = 0.76; 0.71). A simplified risk scoring system showed increasing
      possibility for non-specific spinal pain depending on the number of the
      identified risk factors (chi2 = 65.0; df = 4; p < 0.001). CONCLUSION: Seven
      significant risk factors of non-specific spinal pain in childhood were identified
      using the new, easy to use and reliable PRQ which makes it possible to stratify
      the children according to their individual risk. These slides can be retrieved
      under Electronic Supplementary Material.

PMID- 29450643
TI  - Variants in FIX propeptide associated with vitamin K antagonist hypersensitivity:
      functional analysis and additional data confirming the common founder mutations.
AB  - One of the most common and unwanted side effects during oral anticoagulant
      therapy (OAT) is bleeding complications. In rare cases, vitamin K antagonist
      (VKA)-related bleeding events are associated with mutations affecting the F9
      propeptide at amino acid position 37 due to a substitution of alanine to either
      valine or threonine. Based on our actual cohort of 18 patients, we update the
      knowledge on this rare phenotype and its origin. A founder mutation for both
      variants was reconfirmed by haplotype analysis of intronic and extragenic short
      tandem repeat (STR) polymorphisms with a higher prevalence in Switzerland than in
      other regions of Europe. Screening of healthy individuals for the presence of
      these F9 gene mutations did not identify any of these variants, thus proving the
      rare occurrence of this genotype. Furthermore, both variants were expressed in
      vitro and warfarin dose responses were studied. Our warfarin dose response
      analysis confirmed higher sensitivity of both variants to warfarin with the
      effect being more apparent for Ala37Thr. Thus, although F9 propeptide mutation
      associated hypersensitivity to VKA is a rare phenomenon, awareness towards this
      bleeding phenotype is important to identify patients at risk.

PMID- 29450644
TI  - PI3K/Akt inhibitor LY294002 potentiates homoharringtonine antimyeloma activity in
      myeloma cells adhered to stromal cells and in SCID mouse xenograft.
AB  - Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits multiple
      myeloma (MM) cells both in vitro and in vivo. Our prior study demonstrated that
      the potency of HHT in MM cells was compromised significantly when myeloma cells
      were co-cultured with BM stromal cells. This study aimed to investigate whether
      PI3K/Akt inhibitor LY294002 could potentiate the antimyeloma activity of HHT
      against MM cells adhered to BM stromal cells and in vivo xenograft models. A co
      culture system composed of MM cells and human stromal cells was employed to mimic
      MM cells in bone marrow niche. The inhibitory and pro-apoptotic effect of HHT and
      LY294002 was determined by CCK-8 assay or flow cytometry. Expression of PI3K/Akt
      signaling molecules and anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1)
      was assessed by western blot analysis and/or reverse transcription real-time
      quantitative PCR (RT-qPCR). MM xenografts were used to evaluate antitumor effect
      of combined therapy with HHT and LY294002. Adhesion to BM stromal cells rendered
      MM cells resistant to HHT whereas silencing Mcl-1 partly reversed the resistance.
      LY294002 induced apoptosis in MM cells and potentiated the antimyeloma effects of
      HHT by inhibiting the PI3K/Akt signal pathway which was abnormally activated
      during adhesion. LY294002 also enhanced the antimyeloma effect of HHT in in vivo
      xenograft models. These findings suggest that activation of PI3K/Akt signal
      pathway was responsible for the resistance to HHT in MM cells adhered to stromal
      cells. LY294002 can potentiate the antimyeloma activity of HHT both in vitro and
      in vivo, which may represent a new clinical treatment in MM.

PMID- 29450645
TI  - Brain c-fos expression patterns induced by emotional stressors differing in
      nature and intensity.
AB  - Regardless of its particular nature, emotional stressors appear to elicit a
      widespread and roughly similar brain activation pattern as evaluated by c-fos
      expression. However, their behavioral and physiological consequences may strongly
      differ. Here we addressed in adult male rats the contribution of the intensity
      and the particular nature of stressors by comparing, in a set of brain areas, the
      number of c-fos expressing neurons in response to open-field, cat odor or
      immobilization on boards (IMO). These are qualitatively different stressors that
      are known to differ in terms of intensity, as evaluated by biological markers. In
      the present study, plasma levels of the adrenocorticotropic hormone (ACTH)
      demonstrated that intensity increases in the following order: open-field, cat
      odor and IMO. Four different c-fos activation patterns emerged among all areas
      studied: (i) positive relationship with intensity (posterior-dorsal medial
      amygdala, dorsomedial hypothalamus, lateral septum ventral and paraventricular
      nucleus of the hypothalamus), (ii) negative relationship with intensity
      (cingulate cortex 1, posterior insular cortex, dorsal striatum, nucleus accumbens
      and some subdivisions of the hippocampal formation); (iii) activation not
      dependent on the intensity of the stressor (prelimbic and infralimbic cortex and
      lateral and basolateral amygdala); and (iv) activation specifically associated
      with cat odor (ventromedial amygdala and ventromedial hypothalamus). Histone 3
      phosphorylation at serine 10, another neuronal activation marker, corroborated c
      fos results. Summarizing, deepest analysis of the brain activation pattern elicit
      by emotional stressor indicated that, in spite of activating similar areas, each
      stressor possess their own brain activation signature, mediated mainly by
      qualitative aspects but also by intensity.

PMID- 29450647
TI  - RNA versus protein toxicity in C9orf72 ALS/FTLD.

PMID- 29450646
TI  - Evidence of amyloid-beta cerebral amyloid angiopathy transmission through
      neurosurgery.
AB  - Amyloid-beta (Abeta) is a peptide deposited in the brain parenchyma in
      Alzheimer's disease and in cerebral blood vessels, causing cerebral amyloid
      angiopathy (CAA). Abeta pathology is transmissible experimentally in animals and
      through medical procedures in humans, such as contaminated growth hormone or dura
      mater transplantation in the context of iatrogenic prion disease. Here, we
      present four patients who underwent neurosurgical procedures during childhood or
      teenage years and presented with intracerebral haemorrhage approximately three
      decades later, caused by severe CAA. None of these patients carried pathogenic
      mutations associated with early Abeta pathology development. In addition, we
      identified in the literature four patients with a history of neurosurgical
      intervention and subsequent development of CAA. These findings raise the
      possibility that Abeta pathology may be transmissible, as prion disease is,
      through neurosurgical procedures.

PMID- 29450648
TI  - World Health Organization 4th edition of head and neck tumor classification:
      insight into the consequential modifications.

PMID- 29450649
TI  - Plant species occurrence patterns in Eurasian grasslands reflect adaptation to
      nutrient ratios.
AB  - Previous studies of Eurasian grasslands have suggested that nutrient ratios,
      rather than absolute nutrient availabilities and associated productivity, may be
      driving plant species richness patterns. However, the underlying assumption that
      species occupy distinct niches along nutrient ratio gradients remains to be
      tested. We analysed plant community composition and nutrient status of 644
      Eurasian wet grassland plots. The importance of nutrient ratios driving variation
      in species composition was analysed using ordination methods (DCA and CCA).
      Subsequently, we assessed the niche position and width along the most important
      nutrient ratio gradient [N:P] for each species. We found that the N:P ratio
      explained part of the variation in species composition independent from
      conventional explanatory variables. The N:P ratio explained less variation than
      soil moisture or pH, but more than productivity or the availability of N and P
      separately, highlighting its importance for grassland species composition.
      Species occupied distinct niches along the N:P gradient, and species' niche
      widths decreased toward extreme nutrient limitation. After correcting for niche
      position, there was no overall difference in niche width between endangered and
      non-endangered species. Surprisingly, endangered species with niche optima at the
      extreme P-limited end of the gradient had broader niches than their non
      endangered counterparts. As species occupied distinct niches along a nutrient
      ratio gradient, future grassland conservation efforts may benefit from targeting
      changes in nutrient ratios, i.e. the balance between N and P, rather than only
      focussing on a general reduction in nutrient availability. However, what
      management interventions can be used for this purpose remains unclear.

PMID- 29450651
TI  - Who will remain tremor dominant? The possible role of cognitive reserve in the
      time course of two common Parkinson's disease motor subtypes.
AB  - In a prospective 5-year study among Parkinson's disease (PD) tremor-dominant (TD)
      patients, we investigated who will remain TD and who will later convert into the
      postural instability gait difficulty (PIGD) phenotype. At follow-up, 38% were
      still considered TD. At baseline the TD non-convertors had more years of
      education and better cognitive function than the convertors and significantly
      smaller deterioration in gait, balance, cognitive function and other non-motor
      symptoms. These results highlight the potential role of cognition in protecting
      against the development of PIGD symptoms.

PMID- 29450653
TI  - Microdialysis as a useful tool to detect cerebral metabolic crises.

PMID- 29450652
TI  - Enhanced Tumor Diagnostic and Therapeutic Effect of Mesoporous Silica
      Nanoparticle-Mediated Pre-targeted Strategy.
AB  - PURPOSE: Improving the targeting efficiency of imaging agents or anticancer drugs
      has become essential in the current primary mission to enhance the diagnostic or
      therapeutic effects. To improve the tumor diagnosis and therapy effect, a
      promising drug-delivery and targeting strategy was established based on the
      bioorthogonal chemistry. METHOD: The delivery system was composed of the pre
      targeting carrier Biotin-MSNs-DBCO nanoparticles and the azido cargoes. The
      fluorescence probe 1-(3-azidopropyl) fluorescein (FITC-N3) and ruthenium N
      heterocyclic carbene complex N3-S-S-NHC-Ru were synthesized and served as the
      tumor imaging and therapy probes, respectively. The cell imaging and viability
      was investigated by the Biotin-MSNs-DBCO pre-targeted for 4 h in colonic
      carcinoma (HeLa) cells. RESULTS: For the tumor cell imaging, Biotin-MSNs-DBCO
      could react with FITC-N3 rapidly and completely in 20 min with 93% yields. The
      fluorescence intensity of tumor cells was obviously increased by the Biotin-MSNs
      DBCO pre-targeted. The cytotoxicity of the ruthenium complex N3-S-S-NHC-Ru was
      significantly improved appropriately three times with the IC50 (half inhibitory
      concentration) value of 6.68 +/- 1.29 MUM and enhancement of the mitochondrial
      dysfunction. CONCLUSIONS: The pre-targeting nanoparticle Biotin-MSNs-DBCO could
      selectively capture the azido compounds in tumor cells, which provided a site
      specific target for the cargoes and then resulted in an enhancement of diagnostic
      or therapeutic effects.

PMID- 29450650
TI  - Access to the CNS: Biomarker Strategies for Dopaminergic Treatments.
AB  - Despite substantial research carried out over the last decades, it remains
      difficult to understand the wide range of pharmacological effects of dopaminergic
      agents. The dopaminergic system is involved in several neurological disorders,
      such as Parkinson's disease and schizophrenia. This complex system features
      multiple pathways implicated in emotion and cognition, psychomotor functions and
      endocrine control through activation of G protein-coupled dopamine receptors.
      This review focuses on the system-wide effects of dopaminergic agents on the
      multiple biochemical and endocrine pathways, in particular the biomarkers (i.e.,
      indicators of a pharmacological process) that reflect these effects. Dopaminergic
      treatments developed over the last decades were found to be associated with
      numerous biochemical pathways in the brain, including the norepinephrine and the
      kynurenine pathway. Additionally, they have shown to affect peripheral systems,
      for example the hypothalamus-pituitary-adrenal (HPA) axis. Dopaminergic agents
      thus have a complex and broad pharmacological profile, rendering drug development
      challenging. Considering the complex system-wide pharmacological profile of
      dopaminergic agents, this review underlines the needs for systems pharmacology
      studies that include: i) proteomics and metabolomics analysis; ii) longitudinal
      data evaluation and mathematical modeling; iii) pharmacokinetics-based
      interpretation of drug effects; iv) simultaneous biomarker evaluation in the
      brain, the cerebrospinal fluid (CSF) and plasma; and v) specific attention to
      condition-dependent (e.g., disease) pharmacology. Such approach is considered
      essential to increase our understanding of central nervous system (CNS) drug
      effects and substantially improve CNS drug development.

PMID- 29450654
TI  - Visualizing protoporphyrin IX formation in the dura tail of meningiomas by mass
      spectrometry imaging.
AB  - BACKGROUND: The advantages of 5-aminolevulinacid (5-ALA)-induced fluorescence
      guided surgery in meningiomas are increasingly discussed. In this context,
      despite detectable tumor tissue in histopathologial analyses, no fluorescence was
      shown at the dura tail using the standard operating microscope. Thus, 5-ALA
      metabolism in this surgically important site remains unknown but needs to be
      elucidated when further evaluating indications of fluorescence-guided surgery in
      meningiomas. METHOD: We here present the spatially resolved identification of
      protoporphyrin IX (PpIX) in sphenoid ridge meningioma cryosections from a patient
      who underwent fluorescence-guided microsurgery using molecular imaging analysis
      by matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI
      MS/MS). RESULTS: Despite a strong fluorescence of the main tumor, no fluorescence
      could be detected at the dura tail using the standard operating microscope (blue
      light, 405 nm). However, histopathological analyses clearly showed meningioma
      tissue. Remarkably, MALDI-MS/MS analysis revealed PpIX formation also at the non
      fluorescing dura tail. However, no PpIX was detected in the tumor free dura
      mater. CONCLUSION: MALDI-MS/MS visualized a selective accumulation of PpIX within
      the tumor tissue including the dura tail. Thus, absence of fluorescence in the
      dura tail as visualized by the operating microscope is not caused by the lack of
      PpIX formation.

PMID- 29450656
TI  - Laparoscopic subtotal gastrectomy in morbid obese patients: a valid option to
      laparoscopic gastric bypass in particular circumstances (prospective study).
AB  - BACKGROUND: Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) without resection of
      the distal stomach is largely performed over the world for morbid obesity.
      Potential risk of gastric remnant carcinoma development has been suggested.
      PURPOSE: To present the results obtained after LRYGB with resection of distal
      stomach. METHOD: This prospective study includes 400 consecutive patients. The
      mean body weight was 105.9 +/- 16.8 Kg (range 83-145 kg), and body mass index
      (BMI) was 38.5 +/- 4.4 kg/m2 (32.9-50.3). Postoperative morbid-mortality and
      follow-up were analyzed. RESULTS: Operative time was 128.5 +/- 18.7 min, hospital
      discharge occurred at 3rd postoperative day, postoperative complications occurred
      in 9.25%, early surgical complications were observed in 3% and medical
      complications 4%, late surgical complications occurred 2.25%, no mortality was
      observed. At 1 year follow-up, BMI was 25.3 +/- 2.7 kg/m2 with % of weight loss
      (%WL) of 84.6 + 19.1%. At five years follow-up very similar values were observed.
      CONCLUSION: The results obtained after LRYGB with resection of distal stomach are
      similar to results published after non resection LRYGB regarding early and late
      results and can be indicated in high risk areas of gastric carcinoma.

PMID- 29450655
TI  - Transcription factors network in root endosymbiosis establishment and
      development.
AB  - Root endosymbioses are mutualistic interactions between plants and the soil
      microorganisms (Fungus, Frankia or Rhizobium) that lead to the formation of
      nitrogen-fixing root nodules and/or arbuscular mycorrhiza. These interactions
      enable many species to survive in different marginal lands to overcome the
      nitrogen-and/or phosphorus deficient environment and can potentially reduce the
      chemical fertilizers used in agriculture which gives them an economic, social and
      environmental importance. The formation and the development of these structures
      require the mediation of specific gene products among which the transcription
      factors play a key role. Three of these transcription factors, viz., CYCLOPS,
      NSP1 and NSP2 are well conserved between actinorhizal, legume, non-legume and
      mycorrhizal symbioses. They interact with DELLA proteins to induce the expression
      of NIN in nitrogen fixing symbiosis or RAM1 in mycorrhizal symbiosis. Recently,
      the small non coding RNA including micro RNAs (miRNAs) have emerged as major
      regulators of root endosymbioses. Among them, miRNA171 targets NSP2, a TF
      conserved in actinorhizal, legume, non-legume and mycorrhizal symbioses. This
      review will also focus on the recent advances carried out on the biological
      function of others transcription factors during the root pre-infection/pre
      contact, infection or colonization. Their role in nodule formation and AM
      development will also be described.

PMID- 29450657
TI  - In silico identification of small molecules as novel LXR agonists for the
      treatment of cardiovascular disease and cancer.
AB  - Liver X receptor (LXR), a member of the nuclear receptor superfamily, mainly
      serves as a reverse cholesterol transporter in lipid metabolism. It has been
      demonstrated that LXR is a promising target for the treatment of cardiovascular
      diseases. LXR is also involved in cancer metabolism, glucose homeostasis,
      immunity, and various physiological processes. The antitumor function of LXR has
      become of great interest to researchers in recent years. However, while it is
      believed that activating LXR with small molecules could be a promising approach
      to cancer treatment, effective drugs that target LXR are yet to be reported. To
      find compounds that are potentially capable of activating LXR, we utilized a high
      throughput screening method to search the MolMall database for suitable
      compounds. Seven candidates with lower GB/SA Hawkins scores than the reference
      ligand T0901317 were identified. Based on the results of molecular dynamics (MD)
      simulations, binding free energy analysis, and an analysis of the agonism
      mechanism, ZINC90512020 and ZINC3845032 were predicted to have high affinities
      for LXR and high relative stabilization, and were therefore selected as potential
      LXR agonists. Both of these compounds will undergo further development with a
      view to utilizing them for the treatment of LXR-related cardiovascular diseases
      or cancers.

PMID- 29450659
TI  - Social Factors in the Development of Chronic Rhinosinusitis: a Systematic Review.
AB  - PURPOSE OF REVIEW: In an era where prevention is paramount, understanding social
      factors for chronic rhinosinusitis (CRS) may facilitate preventive interventions
      that mitigate risk factors associated with the initiation or progression of the
      disease. RECENT FINDINGS: Both passive and active smoking are clearly and
      unequivocally associated with both the incidence and the severity of
      rhinosinusitis, while there an increasing body of evidence linking social
      deprivation and low socioeconomic status with rhinosinusitis and its
      complications. However, overall, only a handful of studies were longitudinal,
      while the available studies suffer from lack of standardized definitions of
      rhinosinusitis. In this systematic review, we assessed the available evidence
      linking CRS with social factors, such as socioeconomic status and class,
      educational status, family status, living and working location and conditions,
      and use of toxins or recreational drugs as well as exercise and diet. Thirty
      studies from 1995 onwards fulfilled our inclusion criteria and were used for this
      review. Social deprivation and low socioeconomic level seem to be directly
      associated with rhinosinusitis, as there are pollutants in living or working
      environment. A clear and direct association between smoking (both active and
      passive) and rhinosinusitis was also shown. However, the link between
      rhinosinusitis and education level, and exercise and diet, if any, seems to be
      more complex.

PMID- 29450658
TI  - Modified Allergens for Immunotherapy.
AB  - PURPOSE OF REVIEW: During the past few decades, modified allergens have been
      developed for use in allergen-specific immunotherapy (AIT) with the aim to
      improve efficacy and reduce adverse effects. This review aims to provide an
      overview of the different types of modified allergens, their mechanism of action
      and their potential for improving AIT. RECENT FINDINGS: In-depth research in the
      field of allergen modifications as well as the advance of recombinant DNA
      technology have paved the way for improved diagnosis and research on human
      allergic diseases. A wide range of structurally modified allergens has been
      generated including allergen peptides, chemically altered allergoids, adjuvant
      coupled allergens, and nanoparticle-based allergy vaccines. These modified
      allergens show promise for the development of AIT regimens with improved safety
      and long-term efficacy. Certain modifications ensure reduced IgE reactivity and
      retained T cell reactivity, which facilities induction of immune tolerance to the
      allergen. To date, multiple clinical trials have been performed using modified
      allergens. Promising results were obtained for the modified cat, grass and birch
      pollen, and house dust mite allergens. The use of modified allergens holds
      promise for improving AIT efficacy and safety. There is however a need for larger
      clinical studies to reliably assess the added benefit for the patient of using
      modified allergens for AIT.

PMID- 29450660
TI  - Protein nutritional value, polyphenols and antioxidant properties of corn
      fermented with Agaricus brasiliensis and Agaricus bisporus.
AB  - Solid-state fermentation (SSF) with Agaricus brasiliensis and Agaricus bisporus
      on corn was carried out. The results showed that SSF with the two fungi made up
      the deficiency of tryptophan in corn and improved the protein nutritional value
      of corn. The conjugated polyphenols contents in fermented corn decreased and free
      polyphenols (FPP) contents increased. FPP contents in corn fermented with the two
      fungi reached respectively 25 and 88 times of control, total polyohenols contents
      reached respectively 1.4 and 3.3 times of control. The antioxidant properties
      (i.e. 1,1-diphenyl-2-picrylhydrazyl radical scavenging capacity, reducing power,
      ferrous ion chelating ability and superoxide anion radical scavenging ability) of
      fermented corn were improved significantly. SSF with A. bisporus was more
      favorable to the enhancement in protein nutritional value and antioxidant
      properties of corn than that of A. brasiliensis. The results indicated that SSF
      with the two fungi could upgrade the protein nutritional value, FPP content and
      antioxidant properties of corn.

PMID- 29450661
TI  - Monitoring water quality in a hypereutrophic reservoir using Landsat ETM+ and OLI
      sensors: how transferable are the water quality algorithms?
AB  - The launch of the Landsat 8 in February 2013 extended the life of the Landsat
      program to over 40 years, increasing the value of using Landsat to monitor long
      term changes in the water quality of small lakes and reservoirs, particularly in
      poorly monitored freshwater systems. Landsat-based water quality hindcasting
      often incorporate several Landsat sensors in an effort to increase the temporal
      range of observations; yet the transferability of water quality algorithms across
      sensors remains poorly examined. In this study, several empirical algorithms were
      developed to quantify chlorophyll-a, total suspended matter (TSM), and Secchi
      disk depth (SDD) from surface reflectance measured by Landsat 7 ETM+ and Landsat
      8 OLI sensors. Sensor-specific multiple linear regression models were developed
      by correlating in situ water quality measurements collected from a semi-arid
      eutrophic reservoir with band ratios from Landsat ETM+ and OLI sensors, along
      with ancillary data (water temperature and seasonality) representing ecological
      patterns in algae growth. Overall, ETM+-based models outperformed (adjusted R2
      chlorophyll-a = 0.70, TSM = 0.81, SDD = 0.81) their OLI counterparts (adjusted R2
      chlorophyll-a = 0.50, TSM = 0.58, SDD = 0.63). Inter-sensor differences were most
      apparent for algorithms utilizing the Blue spectral band. The inclusion of water
      temperature and seasonality improved the power of TSM and SDD models.

PMID- 29450663
TI  - Children's Doctor Games and Nudity at Danish Childcare Institutions.
AB  - This article presents the first Danish study of the acceptance of children's
      nudity and sexuality at Danish childcare institutions. The study revealed an
      important cultural shift in the attitude toward children's nudity and sexual
      games, the so-called doctor games. Although these were quite accepted at Danish
      childcare institutions until the beginning of this century, the study showed that
      new, pervasive regulations had been established to control the child's body and
      its sexuality. A new discourse revealed that fear of child sexual abuse, in
      particular, had influenced views of children's sexual games and nudity and that,
      at times, the child itself was viewed as a potential threat to other children.
      This marks a new development in Denmark, internationally known for its
      broadmindedness, and this article discusses the background to this cultural shift
      in the institutions, and possible implications for the children.

PMID- 29450662
TI  - Preconception Counseling for Adolescents and Young Adults with Diabetes: a
      Literature Review of the Past 10 Years.
AB  - PURPOSE OF REVIEW: Women with diabetes who have unplanned pregnancies and
      uncontrolled blood sugars are at a higher risk for maternal and fetal morbidities
      and mortalities. Preconception counseling (PC) has been shown to decrease the
      risks and improve health outcomes. From 2009 to 2017, the American Diabetes
      Association has recommended that preconception counseling be given at each clinic
      visit for all women with diabetes of childbearing age starting at puberty (prior
      to sexual debut). RECENT FINDINGS: This article reports both national and
      international progress in PC efforts for adolescents and young adults (12-34
      years) with diabetes over the past decade. Twenty-eight publications were
      identified and included in this article (11 were research, 12 clinical
      guidelines, and 5 reviews). Despite recommendations to start PC at puberty, only
      four studies had interventions that targeted the adolescent and young adult age
      group. Three of them were associated with the same PC awareness program. Positive
      outcomes were reported in all of these studies. Greater family vigilance was
      observed in a long-term follow-up of a cohort of women who received PC as teens.
      Adolescents should receive awareness PC. More early PC interventions and cohort
      follow-up studies are needed among adolescents and young adults, using technology
      that appeals to this age group. Programs should be expanded to include other
      populations like males with diabetes and females from other cultures and
      religions that would require program modification.

PMID- 29450664
TI  - Radiographic study of mandibular third molars: evaluation of the position and
      root anatomy in Brazilian population.
AB  - OBJECTIVES: The root anatomy and position of mandibular third molars are
      important factors in assessing the level of difficulty of surgical removal
      procedures. In this light, this study aims to identify the most frequent position
      and the root anatomy of mandibular third molars. METHODS: The study sample
      comprised 1205 mandibular third molars from 710 panoramic radiographs evaluated.
      Regarding the position, all of them were based on Pell and Gregory's and Winter's
      classifications. The root anatomy was classified according to the type and number
      of roots, as well as the presence of laceration, fusion, or divergence. Gender
      and the quadrant were also considered. Following an interexaminer analysis, a
      statistical analysis was performed using the Kappa test. RESULTS: The results
      showed that the IA (40.3%) and mesioangular (53.8%) position was predominant in
      mandibular third molars. Regarding the anatomy, the most common were two roots
      (98.3%), of the conical simple type (88.9%), with absence of laceration (89.2%),
      divergence (84%), and fusion (80%). CONCLUSION: The present study showed that the
      most prevalent mandibular third molar type in Brazilian patients was the IA and
      mesioangular position, with simple root anatomy. The result of this study can
      assist oral surgeons to better plan and assess the level of difficulty of
      surgical removal procedures.

PMID- 29450665
TI  - Biochemical pathways and enhanced degradation of di-n-octyl phthalate (DOP) in
      sequencing batch reactor (SBR) by Arthrobacter sp. SLG-4 and Rhodococcus sp. SLG
      6 isolated from activated sludge.
AB  - Two bacterial strains designated as Arthrobacter sp. SLG-4 and Rhodococcus sp.
      SLG-6, capable of utilizing di-n-octyl phthalate (DOP) as sole source of carbon
      and energy, were isolated from activated sludge. The analysis of DOP degradation
      intermediates indicated Arthrobacter sp. SLG-4 could completely degrade DOP.
      Whereas DOP could not be mineralized by Rhodococcus sp. SLG-6 and the final
      metabolic product was phthalic acid (PA). The proposed DOP degradation pathway by
      Arthrobacter sp. SLG-4 was that strain SLG-4 initially transformed DOP to PA via
      de-esterification pathway, and then PA was metabolized to protocatechuate acid
      and eventually converted to tricarboxylic acid (TCA) cycle through meta-cleavage
      pathway. Accordingly, Phthalate 3,4-dioxygenase genes (phtA) responsible for PA
      degradation were successfully detected in Arthrobacter sp. SLG-4 by real-time
      quantitative PCR (q-PCR). q-PCR analysis demonstrated that the quantity of
      phthalate 3,4-dioxygenase was positively correlated to DOP degradation in SBRs.
      Bioaugmentation by inoculating DOP-degrading bacteria effectively shortened the
      start-up of SBRs and significantly enhanced DOP degradation in bioreactors. More
      than 91% of DOP (500 mg L-1) was removed in SBR bioaugmented with bacterial
      consortium, which was double of the control SBR. This study suggests
      bioaugmentation is an effective and feasible technique for DOP bioremediation in
      practical engineering.

PMID- 29450667
TI  - A risk prediction model to allow personalized screening for cervical cancer.
AB  - IMPORTANCE: Cervical cancer screening guidelines are in evolution. Current
      guidelines do not differentiate recommendations based on individual patient risk.
      OBJECTIVE: To derive and validate a tool for predicting individualized
      probability of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) at a
      single time point, based on demographic factors and medical history. DESIGN: The
      study design consisted of an observational cohort with hierarchical generalized
      linear regression modeling. SETTING: The study was conducted in a setting of 33
      primary care practices from 2004 to 2010. PARTICIPANTS: The participants of the
      study were women aged >= 30 years. MAIN OUTCOME AND MEASURES: CIN2+ was the main
      outcome on biopsy, and the following predictors were included: age, race, marital
      status, insurance type, smoking history, median income based on zip code, prior
      human papilloma virus (HPV) results. RESULTS: The final dataset included 99,319
      women. Of these, 745 (0.75%) had CIN2+. The multivariable model had a C-statistic
      of 0.81. All factors but race were independently associated with CIN2+. The model
      categorized women as having below-average CIN2+ risk (0.15% predicted vs. 0.12%
      observed risk), average CIN2+ risk (0.42% predicted vs. 0.36% observed), and
      above-average CIN2+ risk (1.76% predicted vs. 1.85% observed). Before screening,
      women at below-average risk had a risk of CIN2+ well below that of women with
      ASCUS and HPV negative (0.12 vs. 0.20%). CONCLUSIONS AND RELEVANCE: A
      multivariable model using data from the electronic health record was able to
      stratify women across a 50-fold gradient of risk for CIN2+. After further
      validation, use of a similar model could enable more targeted cervical cancer
      screening.

PMID- 29450666
TI  - Recent advances in hyaluronic acid based therapy for osteoarthritis.
AB  - Osteoarthritis is a debilitating disease that has increased in prevalence across
      the world due to the aging population. Currently, physicians use a plethora of
      treatment strategies to try and slow down the progression of the disease, but
      none have been shown to ubiquitously treat and cure the disease. One of the
      strategies uses the high molecular weight molecule hyaluronic acid as either an
      injectable or oral supplement for treatment. Hyaluronic acid (HA) is a relatively
      new treatment that has shown varied results through several clinical trials. It
      can be used as a scaffold for engineering new treatments and several new
      preparations have just been added to the market. A comprehensive search was
      conducted through several search databases according our inclusion and exclusion
      criteria. This review included 44 prospective clinical trial investigating the
      feasibility and efficacy of HA injection for knee, hip, and ankle osteoarthritis.
      This review will take a closer look at hyaluronic acid and its properties, as
      well clinical effectiveness and future options.

PMID- 29450668
TI  - Genetic variation and selection of MHC class I loci differ in two congeneric
      frogs.
AB  - Major histocompatibility complex (MHC) genes encode proteins in the acquired
      immune response pathway that often show distinctive selection-driven patterns in
      wild vertebrate populations. We examined genetic variation and signatures of
      selection in the MHC class I alpha 1 (A1)- and alpha 2 (A2)-domain encoding exons
      of two frog congeners [Agalychnis callidryas (n = 20) and A. lemur (n = 20)] from
      a single locality in Panama. We also investigated how historical demographic
      processes may have impacted MHC genetic diversity by analyzing a neutral
      mitochondrial marker. We found that both MHC domains were highly variable in both
      species, with both species likely expressing three loci. Our analyses revealed
      different signatures of selection between the two species, most notably that the
      A. callidryas A2 domain had experienced positive selection while the A2 domain of
      A. lemur had not. Diversifying selection acted on the same number of A1 and A2
      allelic lineages, but on a higher percentage of A1 sites compared to A2 sites.
      Neutrality tests of mitochondrial haplotypes predominately indicated that the two
      species were at genetic equilibrium when the samples were collected. In addition,
      two historical tests of demography indicated both species have had relatively
      stable population sizes over the past 100,000 years; thus large population size
      changes are unlikely to have greatly influenced MHC diversity in either species
      during this time period. In conclusion, our results suggest that the impact of
      selection on MHC diversity varied between these two closely related species,
      likely due to a combination of distinct ecological conditions and past pathogenic
      pressures.

PMID- 29450669
TI  - Association of TERT-CLPTM1L and 8q24 Common Genetic Variants with Gallbladder
      Cancer Susceptibility and Prognosis in North Indian Population.
AB  - Gallbladder carcinoma (GBC) is one of the common malignancy of the biliary tract.
      Several genome wide and candidate gene studies have reported associations between
      multiple cancer types and single-nucleotide polymorphisms on 5p15.33 and 8q24.21
      loci. However, predisposition potential of these genetic variants has not been
      assessed in GBC. We performed the present study to assess the potential of five
      polymorphisms on 5p15.33 and one on 8q24.21 locus in GBC risk and treatment
      response in patients undergoing chemoradiotherapy. We extracted genomic DNA from
      peripheral blood and genotyped selected SNPs using TaqMan allelic discrimination
      assays in 523 GBC cases and 274 controls from the north-Indian population.
      Statistical tests were performed to assess the association of selected common
      genetic variants with gallbladder cancer susceptibility and prognosis. Binary
      logistic regression analysis showed significant association of TERT rs2736100C >
      A [OR(CI) = 0.690(0.515-0.924), p value = 0.013], CLPTM1L rs401681C > T [OR(CI) =
      0.586(0.405-0.847), p value = 0.004], and CASC8 rs6983267G > T [OR(CI) =
      1.629(1.215-2.186), p value = 0.001] with GBC risk. Further, using multivariate
      logistic regression, we observed that haplotype CLPTM1L Crs401681Crs31489 TERT
      Trs2853676Ars2736100 MIR4457 Grs4635969 [OR(CI) = 7.52 (1.79-31.52), p value =
      0.0064] is significantly associated with poor treatment response. In survival
      analysis, Kaplan-Meier survival curves showed significantly poor survival and COX
      regression suggested significantly higher hazard ratio in TT genotype carriers of
      CASC8 rs6983267 [OR(CI) = 4.28(1. 07-17.10), p value = 0.040] as compared to
      major allele and heterozygous (GG+GT) genotypes in metastatic GBC cases. The
      study revealed that 5p15.33 and 8q24.21 genetic variants significantly influence
      GBC risk and treatment response in north-Indian population.

PMID- 29450670
TI  - Acetylsalicylic acid enhance tolerance of Phaseolus vulgaris L. to chilling
      stress, improving photosynthesis, antioxidants and expression of cold stress
      responsive genes.
AB  - BACKGROUND: High and low temperatures constitute the most damaging type of
      abiotic stress and limit the survival, and productivity of plants. The present
      study aimed to evaluate the role of exogenous applications of acetylsalicylic
      acid (ASA) in reducing the deleterious effects of cold stress. Phaseolus vulgaris
      L. seedlings were treated with foliar-sprayed ASA at concentrations of 0-3 mM and
      then subjected to chilling stress at 4  degrees C for 2 or 4 days. RESULTS:
      Growth, photosynthesis, biochemical alterations, oxidative damage and antioxidant
      enzyme activities as well as the expression of cold-responsive genes (CBF3
      COR47), were monitored during the experiment. ASA applications substantially
      improved several growth and photosynthetic parameters, including shoot biomass,
      dry weight, and photosynthetic pigments, of P. vulgaris seedlings exposed to
      different durations of chilling stresses. The ASA foliar spray treatments
      significantly (p < 0.05) rescued the growth and photosynthetic pigments of P.
      vulgaris seedlings under different chilling stresses. The total soluble sugars
      markedly increased during 0-4 days of chilling stress following ASA foliar
      spraying. The exogenous application of ASA significantly (p < 0.05) increased the
      accumulation of proline in P. vulgaris seedlings under chilling stress. At the
      gene expression level, ASA significantly (p < 0.05) upregulated the cold
      responsive genes CBF3 and COR47. CONCLUSIONS: As a result, we speculate that, the
      application of exogenous ASA alleviated the adverse effects of chilling stress on
      all measured parameters, and 1 and 2 mM ASA exhibited the greatest effects.

PMID- 29450672
TI  - Response to letter to editor regarding published article-metachronous colorectal
      cancer following segmental or extended colectomy in Lynch syndrome: a systematic
      review and meta-analysis.

PMID- 29450671
TI  - Short-term treatment with metformin reduces hepatic lipid accumulation but
      induces liver inflammation in obese mice.
AB  - The study aimed to evaluate the metabolic and inflammatory effects of short-term
      treatments (10 days) with metformin (MET) on the NAFLD caused by a high-fat diet
      (HFD) in C57BL/6 mice. After the treatment, histological liver slices were
      obtained, hepatocytes and macrophages were extracted and cultured with phosphate
      buffered saline, LPS (2.5 ug/mL) and MET (1 uM) for 24 h. Cytokine levels were
      determined by ELISA. NAFLD caused by the HFD was partially reduced by MET. The
      lipid accumulation induced by the HFD was not associated with liver inflammation;
      however, MET seemed to promote pro-inflammatory effects in liver, since it
      increased hepatic concentration of IL-1beta, TNF-alpha, IL-6, MCP-1 and IFN
      gamma. Similarly, MET increased the concentration of IL-1beta, IL-6 in hepatocyte
      cultures. However, in macrophages culture, MET lowered levels of IL-1beta, IL-6
      and TNF-alpha stimulated by LPS. Overall, MET reduced liver NAFLD but promoted
      hepatocyte increase in pro-inflammatory cytokines, thus, leading to liver
      inflammation.

PMID- 29450673
TI  - Recent advances in enhanced enzyme activity, thermostability and secretion by N
      glycosylation regulation in yeast.
AB  - Yeast has been increasingly used as a host for the expression of enzymes.
      Compared to other expression systems, the yeast expression system has many
      advantages including its suitability for large-scale fermentation and its ability
      to modify enzymes. When expressed in yeast, many recombinant enzymes are N
      glycosylated, and this may play an important role in their activity,
      thermostability and secretion. Although the mechanism underlying this process is
      not clear, the regulation of N-glycosylation by introducing or eliminating N
      glycosylation at specific sites has developed into an important strategy for
      improving the production or catalytic properties of recombinant enzymes. In this
      review, we summarize the recent advances in understanding the effects of N
      glycosylation on the expression and characteristics of recombinant enzymes, and
      discuss novel strategies for regulating N-glycosylation in yeast. We hope that
      this review will help improve the understanding of the expression and the
      catalytic properties of N-glycosylated proteins.

PMID- 29450675
TI  - Lipid-lowering drugs, dyslipidemia, and breast cancer risk in a Medicare
      population.
AB  - PURPOSE: We sought to disentangle the effects of statins and other lipid-lowering
      drugs and the underlying dyslipidemia for which they are prescribed on breast
      cancer risk. METHODS: We conducted a case-control study within the linked
      Surveillance, Epidemiology, and End results (SEER)-Medicare data. Cases were
      women with invasive breast cancer aged 66 + years (N = 30,004) identified by SEER
      registries (years 2007-2011). Controls were women (N = 198,969) identified from a
      5% random sample of Medicare recipients alive and breast cancer free in year of
      selection. Participants had a minimum of 13 months of Part A, Part B non-health
      maintenance organization Medicare and Part D Medicare coverage at least 13 months
      preceding cancer diagnosis/selection. Exposures were assessed until 12 months
      before diagnosis/control selection. Odds ratios (OR) and 99.9% confidence
      intervals (CI) were estimated using adjusted unconditional and multinomial
      logistic regression. RESULTS: ORs of invasive breast cancer associated with
      dyslipidemia, statins, and non-statin lipid-lowering drugs were 0.86 (99.9% CI
      0.81-0.90), 1.07 (99.9% CI 1.03-1.13) and 1.03 (99.9% CI 0.95-1.11),
      respectively. Risk reductions with dyslipidemia were slightly greater when
      untreated than treated and did not vary much by time between dyslipidemia and
      breast cancer diagnosis. Whether treated or untreated, dyslipidemia was
      associated with greater reductions in risk for later stage than earlier stage
      breast cancer (p-heterogeneity < 0.0001). CONCLUSIONS: Lipid-lowering drugs did
      not account for the lower breast cancer risk associated with dyslipidemia. Our
      data do not support using statins or other lipid-lowering drugs to prevent breast
      cancer.

PMID- 29450674
TI  - Risk assessment of pesticides in estuaries: a review addressing the persistence
      of an old problem in complex environments.
AB  - Estuaries, coastal lagoons and other transition ecosystems tend to become the
      ultimate reservoirs of pollutants transported by continental runoff, among which
      pesticides constitute the class of most concern. High amounts of dissolved and
      particulated organic matter greatly contribute to the accumulation of pesticides
      that eventually become trapped in sediments or find their way along food chains.
      Perhaps not so surprisingly, it is common to find elevated levels of pesticides
      in estuarine sediments decades after their embargo. Still, it remains challenging
      to address ecotoxicity in circumstances that invariably imply mixtures of
      contaminants and multiple factors affecting bioavailability. Despite advances in
      methods for detecting pesticides in waters, sediments and organisms, chemical
      data alone are insufficient to predict risk. Many researchers have been opting
      for ex situ bioassays that mimic the concentrations of pesticides in estuarine
      waters and sediments using a range of ecologically relevant model organisms, with
      emphasis on fish, molluscs and crustaceans. These experimental procedures
      unravelled novel risk factors and important insights on toxicological mechanisms,
      albeit with some prejudice of ecological relevance. On the other hand, in situ
      bioassays, translocation experiments and passive biomonitoring strive to spot
      causality through an intricate mesh of confounding factors and cocktails of
      pollutants. Seemingly, the most informative works are integrative approaches that
      combine different assessment strategies, multiple endpoints and advanced
      computational and geographical models to determine risk. State-of-art System
      Biology approaches combining high-content screening approaches involving "omics"
      and bioinformatics, can assist discovering and predicting novel Adverse Outcome
      Pathways that better reflect the cumulative risk of persisting and emerging
      pesticides among the wide range of stressors that affect estuaries.

PMID- 29450676
TI  - Comorbid obstructive sleep apnea and increased risk for sickle cell disease
      morbidity.
AB  - PURPOSE: Sickle cell disease (SCD) imparts an increased risk for obstructive
      sleep apnea (OSA) in childhood. Studies of pediatric SCD have identified an
      increased risk for pain and neurologic complications with comorbid OSA. We
      determined the rate of a broad range of SCD-related medical complications to
      better characterize the spectrum of SCD complications related to OSA. METHODS:
      Retrospective chart review at a single hematology clinic identified 641 youth
      with SCD who received consistent screenings for OSA as part of routine
      hematological health maintenance visits over an 11-year period. Medical
      complication rates in the 136 children with OSA determined by polysomnography
      exams were compared to 136 matched controls at lower risk for OSA due to negative
      OSA screenings or exams. RESULTS: Children with SCD and OSA had higher overall
      rates of SCD complications than low OSA-risk controls; lung morbidity showed the
      largest effect size. Infection, cardiovascular, and neurologic complications
      occurred at higher rates in children with OSA. Children with comorbid OSA had
      higher rates of SCD complications both before and after OSA diagnosis.
      CONCLUSIONS: OSA in children with SCD is associated with higher rates of a broad
      range of SCD complications, including pneumonia and acute chest syndrome. Routine
      screenings, diagnosis, and increased therapeutic intervention for children with
      comorbid OSA could decrease SCD morbidity.

PMID- 29450677
TI  - Correction to: Reliability, Construct and Predictive Validity of the Hong Kong
      Chinese Orebro Musculoskeletal Pain Screening Questionnaire.
AB  - The original version of this article unfortunately contained a mistake.

PMID- 29450678
TI  - Predicting the Effectiveness of Work-Focused CBT for Common Mental Disorders: The
      Influence of Baseline Self-Efficacy, Depression and Anxiety.
AB  - Purpose This study examined who benefits most from a cognitive behavioural
      therapy (CBT)-based intervention that aims to enhance return to work (RTW) among
      employees who are absent due to common mental disorders (CMDs) (e.g., depression,
      anxiety, or adjustment disorder). We researched the influence of baseline work
      related self-efficacy and mental health (depressive complaints and anxiety) on
      treatment outcomes of two psychotherapeutic interventions. Methods Using a quasi
      experimental design, 12-month follow-up data of 168 employees were collected.
      Participants either received work-focused cognitive behavioural therapy (W-CBT)
      that integrated work aspects early into the treatment (n = 89) or regular
      cognitive behavioural therapy (R-CBT) without a focus on work (n = 79). Results
      Compared with R-CBT, W-CBT resulted in a faster partial RTW, irrespective of
      baseline self-efficacy. Among individuals with high self-efficacy, W-CBT also
      resulted in faster full RTW. The effectiveness of W-CBT on RTW did not depend on
      baseline depressive complaints or anxiety. The decline of mental health
      complaints did not differ between the two interventions, nor depended on baseline
      self-efficacy or mental health. Conclusions Considering the benefits of W-CBT for
      partial RTW, we recommend this intervention as a preferred method for employees
      with CMDs, irrespective of baseline self-efficacy, depression and anxiety. For
      individuals with high baseline self-efficacy, this intervention also results in
      higher full RTW. For those with low self-efficacy, extra exercises or components
      may be needed to promote full RTW.

PMID- 29450679
TI  - Immunoglobulin E-an Innocent Bystander in Host Defense?

PMID- 29450680
TI  - Effects of Silver Nanoparticles on Hematological Parameters and Hepatorenal
      Functions in Laying Japanese Quails.
AB  - Silver nanoparticles (AgNPs) have recently emerged as a powerful agents for
      disinfection in the poultry industry. AgNPs are capable of epithelial barriers
      passing from the route of exposure to the vital organs and cells. This study
      evaluated the effects of AgNPs on organs weights, blood biochemical,
      hematological, and coagulation parameters, antioxidant enzyme activities, and
      histopathological changes and silver concentrations of liver and kidney tissues
      in laying Japanese quails after exposure to the nanoparticles. The layer quails
      were randomly assigned to 4 groups, consisting of six replicates, three quails
      each. The treatments included 0, 4, 8, and 12 mg/L of AgNPs in daily drinking
      water for 30 weeks. AgNPs decreased the relative weight of liver, ileum and large
      intestine (P < 0.05). Administration of AgNPs elevated plasma fibrinogen while
      decreased serum aspartate aminotransferase activity (P < 0.05). The antioxidant
      status of the liver showed that malondialdehyde level, an end product of lipid
      peroxidation, was higher (P < 0.05) and catalase activity was lower (P < 0.05) in
      the quails exposed to AgNPs. The accumulation of silver in the liver and kidney
      tissues were increased in a dose-dependent manner after exposure to AgNPs (P <
      0.05). Histopathological findings showed reduced lipid vacuolization of
      hepatocytes in the 12 mg/L AgNPs treatment. In conclusion, the results indicated
      that AgNPs administration to drinking water can lead to oxidative stress and
      liver damage in laying quails which may be a predisposing for liver dysfunction.

PMID- 29450681
TI  - Factors Related to the Probable PTSD after the 9/11 World Trade Center Attack
      among Asian Americans.
AB  - Despite the fact that Asians constituted a sizeable proportion of those exposed
      to the World Trade Center attack on September 11, 2001 due to its proximity to
      Chinatown and many South Asians working in the nearby buildings, no study had
      focused on examining the mental health impact of the attack in this group. Based
      on data collected by the World Trade Center Health Registry from a sample of 4721
      Asians 2-3 years after the disaster, this study provides a baseline investigation
      for the prevalence and the risk and protective factors for PTSD among Asian
      Americans directly exposed to the attack and compared this population against
      42,862 non-Hispanic Whites. We found that Asians had a higher prevalence of PTSD
      compared to Whites (14.6 vs 11.7%). "Race-specific factors" significantly
      associated to PTSD in the multivariate analyses were noted among
      sociodemographics: higher education was protective for Whites but a risk factor
      for Asians; being employed was protective for Whites but had no effect for
      Asians; and being an immigrant was a risk factor for Whites but had no effect for
      Asians. However, income was a protective factor for both races. Other "universal
      factors" significantly increased the odds of PTSD symptoms but showed no racial
      differences, including exposure to the disaster and the presence of lower
      respiratory symptoms which intensified odds of PTSD by the greatest magnitude
      (3.6-3.9 times). Targeted effort to reach out to Asians is essential for
      prevention and follow up treatment given this group's striking history of
      underutilization of mental health services.

PMID- 29450682
TI  - Italian Adagio: Every Law has Its Loophole.
AB  - The Italian law of December 2010 establishes new criteria and parameters for the
      evaluation of faculty members. The parameters are represented by the number of
      articles published in journals listed in the main international data banks, the
      total number of citations and the h index. Candidates with qualifications at
      least in two out of three parameters may access the national competitions for
      associate or full professor and apply for an academic appointment. This system
      developed with the aim to fight nepotism and promote meritocracy, progressively
      led to the deterioration of the Italian university system. Since promotion in
      academia is strictly dependent on publications the faculty members found the
      solution to get over this system by organizing themselves into large consortia or
      small groups with the purpose of sharing authorship in scientific publications.
      In this way parameter thresholds may be easily reached and even surpassed. An
      Italian adagio says: "Fatta la Legge, Trovato l'Inganno"; "Every law has its
      Loophole". However, there is no science without ethics and researchers must stay
      away from any kind of compromise.

PMID- 29450683
TI  - Common Adverse Effects of Novel Therapies for Multiple Myeloma (MM) and Their
      Management Strategies.
AB  - PURPOSE OF REVIEW: The purpose of this review was to evaluate management
      strategies for common adverse effects of novel therapies in multiple myeloma
      (MM), including immunomodulatory drugs, proteasome inhibitors, monoclonal
      antibodies, and a histone deacetylase inhibitor. RECENT FINDINGS: There are
      several adverse effects that occur across multiple classes of antimyeloma drugs,
      including rash, peripheral neuropathy, infusion reactions, and cardiotoxicity,
      but most can be managed without complete discontinuation of the agent or
      abandonment of the class. Additionally, several agents have critically important
      drug-drug interactions or dose-modification implications in hepatic or renal
      insufficiency that can be easily overlooked, and exacerbate adverse effects. As
      treatment of MM moves from fixed-duration traditional chemotherapy to novel agent
      based regimens, commonly administered continuously until disease progression or
      intolerable toxicities, providers must adopt their management strategies for both
      acute and long-term adverse effects. Early and frequent monitoring for therapy
      related complications, dose adjustments when needed, and timely treatment for
      toxicities are all important steps toward ensuring longevity of treatment from a
      limited array of therapeutic options that currently exist for a disease with a
      relapsing and remitting course.

PMID- 29450684
TI  - Application and impact of run-in studies.
AB  - BACKGROUND: A run-in phase is often employed prior to randomization in a clinical
      trial to exclude non-adherent patients, placebo responders, active drug non
      responders, or patients who do not tolerate the active drug. This may impact the
      generalizability of trial results. OBJECTIVE: To determine if clinical outcomes
      differed between randomized controlled trials with run-in phases compared with
      randomized controlled trials of the same medication without run-in phases.
      DESIGN, PARTICIPANTS: From 2006 to 2014, the Food and Drug Administration
      approved 258 new medications. Sitaglitpin, saxagliptin, linagliptin, and
      alogliptin were among the only drugs with a common mechanism of action that each
      had multiple clinical trials, some of which had run-in phases and some of which
      did not. We identified all published randomized controlled trials for these four
      medications from MEDLINE and EMBASE as well as prior systematic reviews. MAIN
      MEASURES: We extracted key measures of medication efficacy (reduction in
      hemoglobin A1C) and safety (serious adverse events) from qualifying trials. Study
      results were pooled for each medication using random effects meta-analysis. KEY
      RESULTS: We identified 106 qualifying trials for DPP4 inhibitors, of which 88 had
      run-in phases and 18 did not. The average run-in phase duration was 4.0 weeks
      (range 1-21), and 73% of run-in phases administered placebo rather than active
      drug. The reduction in hemoglobin A1C compared to baseline was similar for trials
      with and without run-in phases (0.70%, 95% confidence interval [CI] 0.65-0.75 vs
      0.76%, 95% CI 0.69-0.84, p = 0.27). The proportion of patients with serious
      adverse events was also similar for trials with and without run-in phases (4%,
      95% CI: 3-5% vs 3%, 95% CI: 1-4%, p = 0.35). CONCLUSION: Trials with run-in
      phases provided similar estimates for medication efficacy and safety compared to
      trials without run-in phases. Because run-in phases are costly and time
      consuming, these results call their utility into question for clinical trials of
      short duration.

PMID- 29450685
TI  - Reducing Long-term Opioid Use in the Veterans Health Administration.

PMID- 29450686
TI  - Capsule Commentary on Goddu et. al., Do Words Matter? Stigmatizing Language and
      the Transmission of Bias in the Medical Record.

PMID- 29450687
TI  - Lethal Talk.

PMID- 29450688
TI  - Capsule Commentary on Robinson et al.: A Randomized Trial on the Efficacy of
      Mastery Learning on Primary Care Providers' Melanoma Opportunistic Screening
      Skills and Practice.

PMID- 29450690
TI  - Mortality rates of patients undergoing emergency laparotomy in an Irish
      university teaching hospital.
AB  - INTRODUCTION: Emergency laparotomy (EL) is a commonly performed operation with
      increased morbidity and mortality. Currently, there is a lack of published
      outcomes following emergency laparotomy within an Irish population. The aim of
      this study was to assess our outcomes and compare these to predefined outcomes
      from NELA. METHODS: A review of a prospectively maintained database of all
      patients who underwent an emergency laparotomy between January 1st 2015 and
      October 31st 2016 was performed. Patient demographics, operative indication and
      procedures, preoperative lactate, time of surgery, admission to high dependency
      unit (HDU) and mortality (30- and 90-day mortality) were included. Statistical
      analysis was performed using Minitab V18 with p < 0.05 considered significant.
      RESULTS: One hundred twenty-four emergency operations were performed on 120
      patients. The median age was 60 years. Indications for surgery included the
      following (%): peritonitis (32.45%), obstruction (22.5%), complicated hernia
      (19.1%), mesenteric ischaemia (15%), trauma (4.1%), and acute haemorrhage (3.3%).
      A consultant surgeon and consultant anaesthetist were present at 79 and 78% of EL
      carried out, respectively. Reported 30- and 90-day mortality were 6.66 and 11.6%,
      respectively. Thirty-day mortality was 20% in octogenarians. Index lactate did
      not correlate with mortality (p = 0.43). A significant proportion of mortalities
      had procedures carried out between 6 pm and midnight with the highest mortality
      rate in patients with mesenteric ischaemia (p < 0.05). CONCLUSION: EL is
      associated with high mortality rates. Our mortality figures compare favourably
      with the NELA data. We support the development of a national database to
      facilitate improvements in the quality of care delivered to this high-risk
      cohort.

PMID- 29450691
TI  - Financial impact of inaccurate Adverse Event recording post Hip Fracture surgery:
      Addendum to 'Adverse event recording post hip fracture surgery'.
AB  - INTRODUCTION: A study in 2011 by (Doody et al. Ir Med J 106(10):300-302, 2013)
      looked at comparing inpatient adverse events recorded prospectively at the point
      of care, with adverse events recorded by the national Hospital In-Patient Enquiry
      (HIPE) System. METHODS: In the study, a single-centre University Hospital in
      Ireland treating acute hip fractures in an orthopaedic unit recorded 39 patients
      over a 2-month (August-September 2011) period, with 55 adverse events recorded
      prospectively in contrast to the HIPE record of 13 (23.6%) adverse events. With
      the recent change in the Irish hospital funding model from block grant to an
      'activity-based funding' on the basis of case load and case complexity, the
      hospital financial allocation is dependent on accurate case complexity coding. A
      retrospective assessment of the financial implications of the two methods of
      adverse incident recording was carried out. RESULTS: A total of ?39,899 in
      'missed funding' for 2 months was calculated when the ward-based, prospectively
      collected data was compared to the national HIPE data. Accurate data collection
      is paramount in facilitating activity-based funding, to improve patient care and
      ensure the appropriate allocation of resources.

PMID- 29450692
TI  - Expression of semaphorin class 3 is higher in the proliferative phase on the
      human endometrium.
AB  - PURPOSE: The semaphorins are related to angiogenesis and cell proliferation
      depending on the tissue. The purpose of this study was to assess gene expression
      of class 3 semaphorin (SEMA3A-F) and protein expression of semaphorin 3A (SEMA3A)
      within human endometrium throughout the menstrual cycle. METHODS: Gene expression
      of SEMA3A-F was analyzed by real-time PCR (qRT-PCR) and protein expression of
      SEMA3A was analyzed by ELISA in endometrial biopsies in the proliferative and
      secretory phase of the menstrual cycle. RESULTS: Gene expression of SEMA3A,
      SEMA3C, SEMA3D, and SEMA3E was statistically significant decreased in secretory
      compared to proliferative phase endometrium (p < 0.05). Accordingly, SEMA3A
      protein expression in the secretory phase was lower than protein expression in
      proliferative phase endometrium (p <= 0.05). CONCLUSION: SEMA3A, 3C, 3D, and 3E
      are possibly related to cell proliferation in the endometrium, being more
      expressed in the proliferative phase of the cycle. This finding may stimulate
      studies of class 3 semaphorins as a possible target for treatment of endometrial
      pathologies.

PMID- 29450693
TI  - The effect of assisted reproductive technology on the incidence of birth defects
      among livebirths.
AB  - PURPOSE: Our study objective is to examine the association between births
      conceived with assisted reproductive technology (ART) and birth defects using a
      large database from the United States. METHODS: Using the Centers for Disease
      Control and Prevention's Period-linked birth-infant death data files and fetal
      death database for 2011-2013, we conducted a retrospective cohort study comprised
      of live births that occurred in the USA during that time. Multivariate logistic
      regression was used to estimate the association between ART and birth defects,
      both overall and by specific defects. RESULTS: There were 11,862,780 live births
      between 2011 and 2013. Of these births, 11,791,730 were spontaneous pregnancies
      and 71,050 were conceived by ART, with an increasing trend in incidence of ART
      during the study period and an overall increasing trend of birth defects.
      Overall, infants conceived by ART had a greater risk of having birth defects than
      did infants conceived spontaneously (77/10,000 vs 25/10,000, respectively, OR
      2.14, 95% CI 1.94-2.35). The malformations most commonly associated with ART were
      cyanotic heart defects (OR 2.74, 95% CI 2.42-3.09), cleft lip and/or palate (OR
      1.47, 95% CI 1.14-1.89), and hypospadias (OR 1.77, 95% CI 1.42-2.19). There were
      no differences in risk of omphalocele or neural tube defects between the two
      groups. CONCLUSIONS: There is an overall and type-specific increased risk of
      birth defects in the ART population. Appropriate counseling and specialized
      ultrasound evaluations should be considered in pregnancies conceived by ART.

PMID- 29450694
TI  - Characteristics of women with mixed mass formation after evacuation following
      uterine artery chemoembolization for cesarean scar pregnancy.
AB  - PURPOSE: To explore the efficacy of treatment for early cesarean scar pregnancy
      (CSP) and to evaluate the characteristics of women with subsequent mixed mass
      formation. METHODS: Women with CSP, who received UACE followed by evacuation,
      were retrospectively analyzed. Clinical/sonographic characteristics in patients
      with or without mixed mass formation were compared. RESULTS: From a total of 395
      cases, 105 cases had a pregnancy residual with mixed mass formation. Blood loss
      and subsequent salvage intervention were significantly lower in patients without
      mixed mass, although all women retained their uteri. It required 50 days for the
      mass to resolve, 40 days for beta-hCG concentrations to drop back to normal, and
      61 days for menses to be restored; all of which were significantly longer than
      the same indices in women without a mixed mass. Clinical/sonographic
      characteristics predicting residual mass formation were maximal diameter of
      gestational sac (OR = 1.05, P = 0.001, with a sensitivity and specificity of 68.6
      and 80.3%, respectively), presence of a fetal heart beat (OR = 2.63, P = 0.002,
      with a sensitivity and specificity of 62.9 and 67.2%, respectively), remnant
      myometrial thickness (OR = 108.91, P = 0.001 when thickness was less than 1 mm,
      with a sensitivity and specificity of 42.9% and 96.6%), location of gestational
      sac (OR = 59.20, P = 0.01 for complete type, with a sensitivity and specificity
      of 99.0 and 36.9%), and Doppler signal grading (OR = 8.08, P = 0.013 for Grade
      III, with a sensitivity and specificity of 83.8 and 51.0%). CONCLUSIONS: UACE
      followed by evacuation was effective for CSP and subsequent mixed mass formation
      could be predicted by some clinical/sonographic characteristics.

PMID- 29450689
TI  - The first multicenter, randomized, controlled trial of home telemonitoring for
      Japanese patients with heart failure: home telemonitoring study for patients with
      heart failure (HOMES-HF).
AB  - Home telemonitoring is becoming more important to home medical care for patients
      with heart failure. Since there are no data on home telemonitoring for Japanese
      patients with heart failure, we investigated its effect on cardiovascular
      outcomes. The HOMES-HF study was the first multicenter, open-label, randomized,
      controlled trial (RCT) to elucidate the effectiveness of home telemonitoring of
      physiological data, such as body weight, blood pressure, and pulse rate, for
      Japanese patients with heart failure (UMIN Clinical Trials Registry 000006839).
      The primary end-point was a composite of all-cause death or rehospitalization due
      to worsening heart failure. We analyzed 181 recently hospitalized patients with
      heart failure who were randomly assigned to a telemonitoring group (n = 90) or a
      usual care group (n = 91). The mean follow-up period was 15 (range 0-31) months.
      There was no statistically significant difference in the primary end-point
      between groups [hazard ratio (HR), 0.95; 95% confidence interval (CI), 0.548
      1.648; p = 0.572]. Home telemonitoring for Japanese patients with heart failure
      was feasible; however, beneficial effects in addition to those of usual care were
      not demonstrated. Further investigation of more patients with severe heart
      failure, participation of home medical care providers, and use of a more
      integrated home telemonitoring system emphasizing communication as well as
      monitoring of symptoms and physiological data are required.

PMID- 29450695
TI  - A clinical approach to arrhythmias revisited in 2018 : From ECG over noninvasive
      and invasive electrophysiology to advanced imaging.
AB  - Understanding arrhythmias and their treatment is not always easy. The current
      straightforward approach with catheter ablation and device therapy is an amazing
      achievement, but does not make management of underlying or other cardiac disease
      and pharmacological therapy unnecessary. The goal of this paper is to describe
      how much of the knowledge of the 1980s and early 1990s can and should still be
      applied in the modern treatment of patients with arrhythmias. After an
      introduction, this review will focus on paroxysmal atrial fibrillation and a
      prototype of 'idiopathic' ventricular arrhythmias, two diseases with a striking
      similarity, and will discuss the arrhythmogenesis. The ECG continues to play an
      important role in diagnostics. Both diseases are associated with a structurally
      normal heart; the autonomic nervous system plays an important role in triggering
      arrhythmias at both the atrial and ventricular level.

PMID- 29450696
TI  - Neuroprotective Effects of Melatonin on Experimental Allergic Encephalomyelitis
      Mice Via Anti-Oxidative Stress Activity.
AB  - Multiple sclerosis (MS) is a chronic auto-inflammatory disease of the central
      nervous system (CNS) and hard to heal. This study aimed to investigate the effect
      of melatonin on mice with experimental autoimmune encephalomyelitis (EAE), a
      widely used MS model, and its potential mechanism underlying the action of MT on
      anti-oxidative stress. Female C57BL/6 mice were injected with MOG35-55 peptide to
      set up the EAE model, and for detection of the effect of melatonin (10 mg/kg
      i.p.) on the development and progression of EAE. Combining immunohistochemistry,
      biochemical technology and western blot approaches, the potential molecular
      mechanism of melatonin on EAE was evaluated as the levels of oxidative stress and
      the expression of Nrf2/ARE signal pathway. Our experiments showed a change of
      oxidative stress and Nrf2/ARE pathway expression in different groups,
      demonstrating that oxidative stress is associated with the pathophysiology of
      EAE. The administration of melatonin exerts neuroprotective effects against EAE,
      notably in suppressing the progression of EAE and pathological changes
      (lymphocytic infiltration). Furthermore, the effect of melatonin was probably
      related to decrease of the levels of oxidative stress, by activation of the
      Nrf2/ARE pathway and increased levels of anti-oxidant enzymes HO-1 and NQO1
      expression. So, melatonin may be a promising reagent for intervention for
      multiple sclerosis in the future, and even for other autoimmune diseases.

PMID- 29450698
TI  - Validation of the Japanese Version of the Low Anterior Resection Syndrome Score.
AB  - BACKGROUND: The low anterior resection syndrome (LARS) score is a patient
      reported outcome measure to evaluate the severity of bowel dysfunction after
      rectal cancer surgery by scoring the major symptoms of LARS. The aim of this
      study was to translate the English version of the LARS score into Japanese and to
      investigate the validity and reliability of the LARS score. METHODS: The LARS
      score was translated in Japanese following current international recommendations.
      A total of 149 rectal cancer patients completed the LARS score questionnaire and
      were also asked a single question assessing the impact of bowel function on
      quality of life (QoL). A total of 136 patients answered the LARS score
      questionnaire twice. RESULTS: The Japanese LARS score showed high convergent
      validity, based on its good correlation between the LARS score and QoL (p <
      0.001). The LARS score was able to discriminate between patients according to the
      tumor distance to anal verge (p < 0.001), type of surgery (p < 0.001), and time
      since surgery (p = 0.001). Patients after ultra-low anterior resection and
      intersphincteric resection showed especially high scores. The score also had high
      test-retest reliability (intraclass correlation coefficient: 0.87). CONCLUSION:
      The Japanese LARS score is a valid and reliable tool for measuring LARS. The LARS
      score is appropriate for assessments in postoperative bowel function and
      international comparison. Using this score, patient-reported outcome measures of
      LARS in Japanese patients can be shared internationally. Additional validation
      reports from non-English speaking countries can support the LARS score as a
      worldwide assessment tool for postoperative bowel dysfunction.

PMID- 29450697
TI  - Endogenous Sex Steroids Dampen Neuroinflammation and Improve Outcome of Traumatic
      Brain Injury in Mice.
AB  - The role of biological sex in short-term and long-term outcome after traumatic
      brain injury (TBI) remains controversial. The observation that exogenous female
      sex steroids (progesterone and estrogen) reduce brain injury coupled with a small
      number of clinical studies showing smaller injury in women suggest that sex
      steroids may play a role in outcome from TBI. We used the controlled cortical
      impact (CCI) model of TBI in mice to test the hypothesis that after CCI, female
      mice would demonstrate less injury than male mice, related to the protective role
      of endogenous steroids. Indeed, adult females exhibit histological protection
      (3.7 +/- 0.5 mm3) compared to adult male mice (6.8 +/- 0.6 mm3), and females that
      lacked sex steroids (ovex) showed increased injury compared to intact females.
      Consistent with histology, sensorimotor deficits measured as reduced
      contralateral limb use were most pronounced in male mice (31.9 +/- 6.9% reduced
      limb use) compared to a 12.7 +/- 3.8% reduction in female mice. Ovex mice
      exhibited behavioral deficits similar to males (31.5 +/- 3.9% reduced limb use).
      Ovex females demonstrated increased microglial activation relative to intact
      females in both the peri-injury cortex and the reticular thalamic nucleus. Ovex
      females also demonstrated increased astrogliosis in comparison to both females
      and males in the peri-injury cortex. These data indicate that female sex steroids
      reduce brain sensitivity to TBI and that reduced acute neuroinflammation may
      contribute to the relative protection observed in females.

PMID- 29450699
TI  - Consolidation/Tumor Ratio on Chest Computed Tomography as Predictor of
      Postoperative Nodal Upstaging in Clinical T1N0 Lung Cancer.
AB  - BACKGROUND: In clinical T1N0 peripheral lung cancers, lymph node upstaging is
      occasionally encountered postoperatively. However, nodal upstaging is rare in
      lung cancers presenting as ground-glass opacities. The aim of this study was to
      determine if lymph node upstaging could be reliably extrapolated from parameters
      such the consolidation/tumor ratio of chest computed tomography. METHODS: We
      conducted a retrospective study of 486 patients treated for peripheral clinical
      T1N0 non-small cell lung cancer, each undergoing lobectomy with mediastinal lymph
      node dissection. We compared preoperative variables in the pathologic N0 and
      nodal upstaging groups, analyzing such variables to determine factors predictive
      of lymph node upstaging. RESULTS: Of the 486 patients studied, lymph node
      upstaging occurred in 42 (8.6%). In the upstaging group, the mean nodule diameter
      exceeded that of the pathologic N0 group (2.3 vs 1.9 cm, respectively; p <
      0.001), and the mean consolidation/tumor ratio was larger in the upstaging group
      than the pN0 group (0.95 vs 0.68, respectively; p < 0.001). Nodule diameter and
      consolidation/tumor ratio emerged as significant predictive factors for lymph
      node upstaging after surgery in a multivariate analysis (hazard ratio [HR] 2.259,
      p = 0.039; HR 173.645, p = 0.001, respectively). CONCLUSIONS: Consolidation/tumor
      ratio and nodule diameter are significant predictive factors of postoperative
      lymph node upstaging. The higher the consolidation/tumor ratio and smaller the
      nodule diameter, the less likely the occurrence of postoperative lymph upstaging
      would be in clinical T1N0 peripheral non-small cell lung cancer.

PMID- 29450700
TI  - Which Patients Require Extended Thromboprophylaxis After Colectomy? Modeling Risk
      and Assessing Indications for Post-discharge Pharmacoprophylaxis: Reply.

PMID- 29450701
TI  - Burden, Characteristics and Process of Care Among the Pediatric and Adult Trauma
      Patients in Botswana's Main Hospitals.
AB  - BACKGROUND: Botswana is notable among countries with high rates of Road Traffic
      Collisions (RTC); like many other lower-middle-income countries (LMICs), it lacks
      trauma systems. The World Health Organization recommends 'Essential Trauma Care'
      in countries with no formal trauma systems. The proportion of injuries in
      Emergency Departments and the care process were investigated to gain an overview
      for enabling the design of a relevant LMICs trauma system. METHOD: Blunt and
      penetrating trauma patients were included from three major hospitals, examining
      the proportion of injuries, patient characteristics, the care process and
      comparing these between pediatrics and adults. Data are presented using
      descriptive statistics. RESULTS: The proportion of trauma ranged between 6 and
      10% of Emergency Department cases. Pediatrics constituted 19%, and 59% of all
      patients were male. The median age was 28 years [IQR 17-39] and 8 years [IQR 4
      11] for adults and pediatrics, respectively. The leading causes of injuries were:
      falls in pediatrics (55%) and interpersonal violence in the adults (34%),
      followed by RTC in both children (20%) and adults (30%). The public inter
      hospital vehicles transported 77% of pediatrics and 69% of adults, while formal
      ambulance transported only 9% of pediatrics and 22% of adults. The median
      Emergency Department waiting time for pediatrics was 187 min [IQR 102-397] and
      for adults was 208 min [IQR 100-378]: Most were triaged as non-urgent (70%
      pediatrics and 72% adults), and the majority were discharged (84% pediatrics and
      76% adults). CONCLUSION: The Emergency Department workload of injuries is notably
      high, with differing mechanisms of injury and transport modes between pediatrics
      and adults: Waiting time is severely prolonged for urgent and critical patients.
      Diagnoses, triage categories and patients disposition were similar.

PMID- 29450702
TI  - Establishment and characterization of the NCC-SS1-C1 synovial sarcoma cell line.
AB  - Synovial sarcoma is an aggressive mesenchymal malignancy characterized by unique
      gene fusions. Tissue culture cells are essential tools for further understanding
      tumorigenesis and anti-cancer drug development; however, only a limited number of
      well-characterized synovial sarcoma cell lines exist. Thus, the objective of this
      study was to establish a patient-derived synovial sarcoma cell line. We
      established a synovial sarcoma cell line from tumor tissue isolated from a 72
      year-old female patient. Prepared cells were analyzed for the presence of gene
      fusions by fluorescence in situ hybridization, RT-PCR, and karyotyping. In
      addition, the resulting cell line was characterized by viability, short tandem
      repeat, colony and spheroid formation, and invasion analyses. Differences in gene
      enrichment between the primary tumor and cell line were examined by mass
      spectrometric protein expression profiling and KEGG pathway analysis. Our
      analyses revealed that the primary tumor and NCC-SS1-C1 cell line harbored the
      SS18-SSX1 fusion gene typical of synovial sarcoma and similar proteomics
      profiles. In vitro analyses also confirmed that the established cell line
      harbored invasive, colony-forming, and spheroid-forming potentials. Moreover,
      drug screening with chemotherapeutic agents and tyrosine kinase inhibitors
      revealed that doxorubicin, a subset of tyrosine kinase inhibitors, and several
      molecular targeting drugs markedly decreased NCC-SS1-C1 cell viability. Results
      from the present study support that the NCC-SS1-C1 cell line will be an effective
      tool for sarcoma research.

PMID- 29450703
TI  - Utilization of hepatitis B core antibody positive grafts in living donor liver
      transplantation.
AB  - BACKGROUND: Utilization of liver grafts from hepatitis B core antibody (anti-HBc)
      positive donors carries the risk of reactivation of hepatitis B virus (HBV) in
      recipients because of post-transplant immunosuppressive therapy. METHODS: This
      was a retrospective study of patients who had received liver grafts from anti-HBc
      positive live donors between 2006 and 2016 at our institute. RESULTS: Out of 22
      recipients [all males, mean age 45.4 years (range 18-64 years)], four patients
      were hepatitis B surface antigen (HBsAg) positive preoperatively and received
      entecavir post-transplantation. One among these patients who temporarily stopped
      entecavir had a recurrence of hepatitis B 39 months post-transplantation. Among
      the 13 non-immune [hepatitis B surface antibody (anti-HBs) < 10 mIU/mL]
      recipients, eight were prescribed lamivudine (100 mg daily) as monoprophylaxis.
      Four compliant patients remain negative for HBV so far. Out of the remaining
      four, two died secondary to sepsis unrelated to hepatitis B; two were non
      compliant and developed reactivation of hepatitis B. Lamivudine was missed out in
      five non-immune patients; three of them developed hepatitis B reactivation while
      two remain negative. Anti-HBs titer was immune in five patients. Over a period of
      4 to 8 years follow up, three remain immune without prophylaxis, while two
      expired due to causes unrelated to hepatitis B. Following the detection of
      hepatitis B infection, five patients have been started on tenofovir 300 mg once
      daily. CONCLUSIONS: Anti-HBc positive liver grafts can be safely used for live
      donor liver transplantation. If the recipients are immune preoperatively, they
      can be merely followed up without HBV prophylaxis. However, it is extremely
      important to prophylactically treat the non-immune recipients with an antiviral
      agent lifelong.

PMID- 29450705
TI  - Modeling competence development in the presence of selection bias.
AB  - A major challenge for representative longitudinal studies is panel attrition,
      because some respondents refuse to continue participating across all measurement
      waves. Depending on the nature of this selection process, statistical inferences
      based on the observed sample can be biased. Therefore, statistical analyses need
      to consider a missing-data mechanism. Because each missing-data model hinges on
      frequently untestable assumptions, sensitivity analyses are indispensable to
      gauging the robustness of statistical inferences. This article highlights
      contemporary approaches for applied researchers to acknowledge missing data in
      longitudinal, multilevel modeling and shows how sensitivity analyses can guide
      their interpretation. Using a representative sample of N = 13,417 German
      students, the development of mathematical competence across three years was
      examined by contrasting seven missing-data models, including listwise deletion,
      full-information maximum likelihood estimation, inverse probability weighting,
      multiple imputation, selection models, and pattern mixture models. These analyses
      identified strong selection effects related to various individual and context
      factors. Comparative analyses revealed that inverse probability weighting
      performed rather poorly in growth curve modeling. Moreover, school-specific
      effects should be acknowledged in missing-data models for educational data.
      Finally, we demonstrated how sensitivity analyses can be used to gauge the
      robustness of the identified effects.

PMID- 29450704
TI  - Gulf Arabic nouns and verbs: A standardized set of 319 object pictures and 141
      action pictures, with predictors of naming latencies.
AB  - Standardized pictorial stimuli and predictors of successful picture naming are
      not readily available for Gulf Arabic. On the basis of data obtained from Qatari
      Arabic, a variety of Gulf Arabic, the present study provides norms for a set of
      319 object pictures and a set of 141 action pictures. Norms were collected from
      healthy speakers, using a picture-naming paradigm and rating tasks. Norms for
      naming latencies, name agreement, visual complexity, image agreement,
      imageability, age of acquisition, and familiarity were established. Furthermore,
      the database includes other intrinsic factors, such as syllable length and
      phoneme length. It also includes orthographic frequency values (extracted from
      Aralex; Boudelaa & Marslen-Wilson, 2010). These factors were then examined for
      their impact on picture-naming latencies in object- and action-naming tasks. The
      analysis showed that the primary determinants of naming latencies in both nouns
      and verbs are (in descending order) image agreement, name agreement, familiarity,
      age of acquisition, and imageability. These results indicate no evidence that
      noun- and verb-naming processes in Gulf Arabic are influenced in different ways
      by these variables. This is the first database for Gulf Arabic, and therefore the
      norms collected from the present study will be of paramount importance for
      researchers and clinicians working with speakers of this variety of Arabic. Due
      to the similarity of the Arabic varieties spoken in the Gulf, these different
      varieties are grouped together under the label "Gulf Arabic" in the literature.
      The normative databases and the standardized pictures from this study can be
      downloaded from http://qufaculty.qu.edu.qa/tariq-khwaileh/download-center/ .

PMID- 29450706
TI  - Transitions From Sexual Relationships Into Cohabitation and Beyond.
AB  - Much research on cohabitation has focused on transitions from cohabitation to
      marriage or dissolution, but less is known about how rapidly women progress into
      cohabitation, what factors are associated with the tempo to shared living, and
      whether the timing into cohabitation is associated with subsequent marital
      transitions. We use data from the 2006-2013 National Survey of Family Growth to
      answer these questions among women whose most recent sexual relationship began
      within 10 years of the interview. Life table results indicate that transitions
      into cohabitation are most common early in sexual relationships; nearly one
      quarter of women had begun cohabiting within six months of becoming sexually
      involved. Multivariate analyses reveal important social class disparities in the
      timing to cohabitation. Not only are women from more-advantaged backgrounds
      significantly less likely to cohabit, but those who do cohabit enter shared
      living at significantly slower tempos than women whose mothers lacked a college
      degree. In addition, among sexual relationships that transitioned into cohabiting
      unions, college-educated women were significantly more likely to transition into
      marriage than less-educated women. Finally, although the tempo effect is only
      weakly significant, women who moved in within the first year of their sexual
      relationship demonstrated lower odds of marrying than did women who deferred
      cohabiting for over a year. Relationship processes are diverging by social class,
      contributing to inequality between more- and less-advantaged young adults.

PMID- 29450707
TI  - Gender and the Residential Mobility and Neighborhood Attainment of Black-White
      Couples.
AB  - Including black-white couples in the study of residential stratification
      accentuates gendered power disparities within couples that favor men over women,
      which allows for the analysis of whether the race of male partners in black-white
      couples is associated with the racial and ethnic composition of their
      neighborhoods. I investigate this by combining longitudinal data between 1985 and
      2015 from the Panel Study of Income Dynamics linked to neighborhood- and
      metropolitan-level data compiled from four censuses. Using these data, I assess
      the mobility of black male-white female and white male-black female couples out
      of and into neighborhoods defined respectively by their levels of whites, blacks,
      and ethnoracial diversity. My results show that the race of the male partner in
      black-white couples tends to align with the racial and ethnic composition of the
      neighborhoods where these couples reside. This finding highlights that the racial
      hierarchy within the United States affects the residential mobility and
      attainment of black-white couples, but its influence is conditioned by the race
      and gender composition of these couples.

PMID- 29450708
TI  - Metabolism of Rhizoma coptidis in Human Urine by Ultra-High-Performance Liquid
      Chromatography Coupled with High-Resolution Mass Spectrometry.
AB  - BACKGROUND AND OBJECTIVES: Rhizoma coptidis extract and its alkaloids were
      reported to exhibit various pharmacological activities. However, pharmacokinetics
      investigations indicated that the plasma concentrations of the alkaloids were too
      low to explain their systemic therapeutic actions. Thus, the metabolic profile of
      Rhizoma coptidis in humans is yet to be fully investigated and the present study
      aimed to investigate the metabolic profile of Rhizoma coptidis in human urine
      after oral administration of Rhizoma coptidis extract. METHODS: In this study,
      the metabolism of Rhizoma coptidis at a clinical dose (5 g/60 kg/day) was
      investigated using ultra-high-performance liquid chromatography coupled with high
      resolution LTQ-Orbitrap mass spectrometry. RESULTS: Totally, 30 constituents
      including 7 prototypes, 5 sulfation metabolites and 18 glucuronide conjugates
      were elucidated and identified on the basis of the characteristics of their high
      resolution precursor ions, product ions, and chromatographic retention times in
      human urine. Among the 7 prototypes, 3 prototypes (M20, M26 and M28) were
      identified definitely by comparing with standards. Based on the metabolites
      detected in human urine, a possible metabolic pathway of Rhizoma coptidis in vivo
      was proposed. CONCLUSIONS: The results demonstrated that the metabolic fate of
      Rhizoma coptidis mainly involved sulfation and glucuronidation in human urine and
      the glucuronide conjugate M14 (berberrubinen-9-O-glucuronide) might be a
      pharmacokinetic marker for Rhizoma coptidis alkaloids in humans. This study will
      be helpful to comprehensively understand the metabolic process of Rhizoma
      coptidis and how Rhizoma coptidis shows its pharmacological effects in humans.

PMID- 29450709
TI  - Biofilm formation and potential for iron cycling in serpentinization-influenced
      groundwater of the Zambales and Coast Range ophiolites.
AB  - Terrestrial serpentinizing systems harbor microbial subsurface life. Passive or
      active microbially mediated iron transformations at alkaline conditions in deep
      biosphere serpentinizing ecosystems are understudied. We explore these processes
      in the Zambales (Philippines) and Coast Range (CA, USA) ophiolites, and
      associated surface ecosystems by probing the relevance of samples acquired at the
      surface to in situ, subsurface ecosystems, and the nature of microbe-mineral
      associations in the subsurface. In this pilot study, we use microcosm experiments
      and batch culturing directed at iron redox transformations to confirm
      thermodynamically based predictions that iron transformations may be important in
      subsurface serpentinizing ecosystems. Biofilms formed on rock cores from the
      Zambales ophiolite on surface and in-pit associations, confirming that organisms
      from serpentinizing systems can form biofilms in subsurface environments.
      Analysis by XPS and FTIR confirmed that enrichment culturing utilizing ferric
      iron growth substrates produced reduced, magnetic solids containing siderite,
      spinels, and FeO minerals. Microcosms and enrichment cultures supported organisms
      whose near relatives participate in iron redox transformations. Further, a
      potential 'principal' microbial community common to solid samples in
      serpentinizing systems was identified. These results indicate collectively that
      iron redox transformations should be more thoroughly and universally considered
      when assessing the function of terrestrial subsurface ecosystems driven by
      serpentinization.

PMID- 29450710
TI  - Indicators for imaging in periorbital cellulitis secondary to rhinosinusitis.
AB  - PURPOSE: Our objective was to identify the clinical indicators for subperiosteal
      orbital abscess (SPOA) among patients who present with periorbital cellulitis
      secondary to rhinosinusitis, and to evaluate the need for performing a
      computerized tomography (CT) scan. METHODS: A retrospective cohort study of all
      patients admitted to our tertiary care emergency department between 2006 and 2014
      was conducted. Included were healthy patients with acute periorbital cellulitis
      secondary to rhinosinusitis. Variables analyzed included age, gender, duration of
      symptoms, previous antibiotic therapy, highest recorded temperature, physical
      examination findings, ophthalmologist's examination results, laboratory results,
      and interpretation of imaging studies, when performed. RESULTS: Of the 123
      identified patients, 78 (63%) were males, with a mean age of 4 years (range 1
      70). 68 patients were categorized as Chandler's 1 disease, 2 as Chandler's 2, and
      53 as Chandler's 3. 68 patients underwent a CT scan, of those 53 had SPOA.
      Proptosis and ophthalmoplegia were strongly associated with the presence of an
      abscess (P < 0.001). However, 14 patients with no ophthalmoplegia or proptosis
      who underwent a CT scan were older (mean age, 10 years; P < 0.028), and had
      higher neutrophil count of 78 versus 59% (P = 0.01). This group of patients had a
      clinically rapidly progressive disease, receiving wider broad-spectrum
      antibiotics or had their antibiotic treatment replaced to broader spectrum
      antibiotics through their course of treatment (48.2% compared to only 6.1%).
      CONCLUSIONS: We confirmed that patients with proptosis and/or limitation of
      extraocular movements are at high risk for developing SPOA, yet many do not have
      these predictors. Other features can identify patients who do not have proptosis
      and/or limitation of extraocular movements but do have significant risk of SPOA,
      and in these cases performing an imaging study is strongly suggested.

PMID- 29450711
TI  - Renal fat fraction and diffusion tensor imaging in patients with early-stage
      diabetic nephropathy.
AB  - OBJECTIVE: To investigate the renal fat fraction and water molecular diffusion
      features in patients with early-stage DN using Dixon imaging and diffusion tensor
      imaging (DTI). METHODS: Sixty-one type 2 diabetics (normoalbuminuria: n = 40;
      microalbuminuria: n = 21) and 34 non-diabetic volunteers were included. All
      participants received three-point Dixon imaging and DTI using a 3.0-T magnetic
      resonance imager. The fat fraction [FF] and DTI features [fractional anisotropy
      (FA), apparent diffusion coefficient (ADC), tract counts and length from DTI
      tractography] were collected. All image features were compared between cohorts
      using one-way ANOVA with Bonferroni post-hoc analysis. RESULTS: Renal FF in the
      microalbuminuric group was significantly higher than in the normoalbuminuric and
      control groups (5.6% +/- 1.3%, 4.7% +/- 1.1% and 4.3% +/- 0.5%, respectively; p <
      0.001). Medullary FA in the microalbuminuric group was the lowest (0.31 +/- 0.06)
      in all cohorts. The tract counts and length in the renal medulla were
      significantly lower in the microalbuminuric group than in the other two groups.
      CONCLUSIONS: Dixon imaging and DTI are able to detect renal lipid deposition and
      water molecule diffusion abnormalities in patients with early-stage DN. Both
      techniques have the potential to noninvasively evaluate early renal impairment in
      type 2 diabetes. KEY POINTS: * Dixon imaging demonstrated renal fat deposition in
      early-stage DN; * Renal fractional anisotropy decreased in patients with early
      stage DN; * Renal tractography demonstrated reduced track counts and length in
      early-stage DN.

PMID- 29450712
TI  - Artifacts during the arterial phase of gadoxetate disodium-enhanced MRI: Multiple
      arterial phases using view-sharing from two different vendors versus single
      arterial phase imaging.
AB  - OBJECTIVES: To assess the usefulness of multiple arterial phase (AP) of gadoxetic
      acid-enhanced MRI using view-sharing of two different vendors to reduce transient
      severe motion (TSM) artifact in the AP. METHODS: This retrospective study
      included 298 patients (mean age 63 years) who underwent gadoxetic acid MRI with
      multiple AP from two different vendors; either triple (subcohort A, n=174) or
      quadruple (subcohort B, n=124) AP. 202 patients (143 vs. 59) underwent follow-up
      MRI with single AP. To compare multiple AP with single AP and between subcohorts,
      mean artifact score rated by two observers and frequency of significant artifacts
      were evaluated. Frequency of acquisition of late AP was also assessed. RESULTS:
      There was no difference in mean artifact score (p=0.086) or frequency of
      significant artifacts (p=0.219) between multiple AP and single AP. For the mean
      best score with multiple AP, subcohort B was better than subcohort A (p<0.001).
      Late AP was achieved more often with multiple AP (74.8 %, 98.3 %) than with
      single AP (64.3 %, 64.4 %). CONCLUSION: Multiple AP using different view-sharing
      failed to show differences in TSM artifacts in AP compared to single AP.
      Frequency of acquisition of late AP was higher with multiple AP. Mean best
      artifact score of multiple AP is different depending on view-sharing technique.
      KEY POINTS: * TSM artifacts were not significantly different between multiple AP
      and single AP. * The frequency of acquiring late AP was higher with multiple AP.
      * For multiple APs, TSM artifacts are different according to view-sharing
      technique.

PMID- 29450713
TI  - Radiomic signature as a diagnostic factor for histologic subtype classification
      of non-small cell lung cancer.
AB  - OBJECTIVES: To distinguish squamous cell carcinoma (SCC) from lung adenocarcinoma
      (ADC) based on a radiomic signature METHODS: This study involved 129 patients
      with non-small cell lung cancer (NSCLC) (81 in the training cohort and 48 in the
      independent validation cohort). Approximately 485 features were extracted from a
      manually outlined tumor region. The LASSO logistic regression model selected the
      key features of a radiomic signature. Receiver operating characteristic curve and
      area under the curve (AUC) were used to evaluate the performance of the radiomic
      signature in the training and validation cohorts. RESULTS: Five features were
      selected to construct the radiomic signature for histologic subtype
      classification. The performance of the radiomic signature to distinguish between
      lung ADC and SCC in both training and validation cohorts was good, with an AUC of
      0.905 (95% confidence interval [CI]: 0.838 to 0.971), sensitivity of 0.830, and
      specificity of 0.929. In the validation cohort, the radiomic signature showed an
      AUC of 0.893 (95% CI: 0.789 to 0.996), sensitivity of 0.828, and specificity of
      0.900. CONCLUSIONS: A unique radiomic signature was constructed for use as a
      diagnostic factor for discriminating lung ADC from SCC. Patients with NSCLC will
      benefit from the proposed radiomic signature. KEY POINTS: * Machine learning can
      be used for auxiliary distinguish in lung cancer. * Radiomic signature can
      discriminate lung ADC from SCC. * Radiomics can help to achieve precision medical
      treatment.

PMID- 29450714
TI  - Glypican-1 circulating exosomes: a promising clue to individualize surveillance
      of pancreatic cysts?

PMID- 29450715
TI  - Utility of MRI for cervical spine clearance in blunt trauma patients after a
      negative CT.
AB  - PURPOSE: To determine the utility of cervical spine MRI in blunt trauma
      evaluation for instability after a negative non-contrast cervical spine CT.
      METHODS: A review of medical records identified all adult patients with blunt
      trauma who underwent CT cervical spine followed by MRI within 48 h over a 33
      month period. Utility of subsequent MRI was assessed in terms of findings and
      impact on outcome. RESULTS: A total of 1,271 patients with blunt cervical spine
      trauma underwent both cervical spine CT and MRI within 48 h; 1,080 patients were
      included in the study analysis. Sixty-six percent of patients with a CT cervical
      spine study had a negative study. Of these, the subsequent cervical spine MRI had
      positive findings in 20.9%; 92.6% had stable ligamentous or osseous injuries,
      6.0% had unstable injuries and 1.3% had potentially unstable injuries. For
      unstable injury, the NPV for CT was 98.5%. In all 712 patients undergoing both CT
      and MRI, only 1.5% had unstable injuries, and only 0.42% had significant change
      in management. CONCLUSIONS: MRI for blunt trauma evaluation remains not
      infrequent at our institution. MRI may have utility only in certain patients with
      persistent abnormal neurological examination. KEY POINTS: * MRI has limited
      utility after negative cervical CT in blunt trauma. * MRI is frequently positive
      for non-specific soft-tissue injury. * Unstable injury missed on CT is
      infrequent.

PMID- 29450716
TI  - Could IVIM and ADC help in predicting the KRAS status in patients with rectal
      cancer?
AB  - PURPOSE: To evaluate the diagnostic potential of DW-MRI relative parameters for
      differentiation of rectal cancers with different Kirsten rat sarcoma viral
      oncogene homologue (KRAS) mutation status. METHODS: Fifty-one patients with
      rectal cancer underwent diffusion-weighted MR imaging with eight b values. ADCs
      (including Max-ADC, Min-ADC and Mean-ADC) and IVIM parameters (D, pure diffusion;
      f, perfusion fraction; D*, pseudodiffusion coefficient) were respectively
      calculated by mono- and bi-exponential analysis. Patients were stratified into
      two groups: KRAS wild type and mutant. The DW-MRI-derived parameters between the
      KRAS wild-type group and KRAS mutant group were compared using the Mann-Whitney U
      test. Receiver-operating characteristic (ROC) analysis of discrimination between
      KRAS wild-type and KRAS mutant rectal cancer was performed for the DW-MRI-derived
      parameters. RESULTS: Max-ADC, Mean-ADC and D values were significantly lower in
      the KRAS mutant group than in the KRAS wild-type group, whereas a higher D* value
      was demonstrated in the KRAS mutant group. According to the ROC curve, Mean-ADC
      and D* values showed moderate diagnostic significance with the AUC values of
      0.756 and 0.710, respectively. The cut-off values for Mean-ADC and D* were 1.43 *
      10-3mm2/s and 26.58 * 10-3mm2/s, respectively. CONCLUSION: Rectal cancers had
      distinctive diffusion/perfusion characteristics in different KRAS mutation
      statuses. The DW-MRI-derived parameters, specifically Mean-ADC and D*, show a
      moderate diagnostic significance for KRAS status. KEY POINTS: * Rectal cancers
      with different KRAS mutation statuses demonstrated distinctive
      diffusion/perfusion characteristics. * Max-ADC, Mean-ADC and D values were lower
      in the KRAS mutant group. * A higher D* value was demonstrated in the KRAS mutant
      group. * IVIM-DW MRI may potentially help preoperative KRAS mutant status
      prediction.

PMID- 29450717
TI  - Prediction of infarct size and adverse cardiac outcomes by tissue tracking
      cardiac magnetic resonance imaging in ST-segment elevation myocardial infarction.
AB  - OBJECTIVES: We investigated whether quantification of global left ventricular
      (LV) strain by tissue tracking-CMR (TT-CMR) can estimate the infarct size and
      clinical outcomes in patients with acute myocardial infarction (MI). METHODS: We
      retrospectively registered 247 consecutive patients (58 +/- 12 years; male, 81%)
      who underwent 1.5-T CMR within 1 month after ST-segment elevation MI (median, 4
      days; interquartile range, 3-6 days), and 20 age- and sex-matched controls (58 +/
      11 years; male, 80%). TT-CMR analysis was applied to cine-images to measure
      global LV radial, circumferential and longitudinal peak strains (GRS, GCS and
      GLS, respectively). Adverse cardiac events were defined as cardiac death and
      hospitalization for heart failure. RESULTS: During the follow-up (median, 7.8
      years), 20 patients (8.1%) experienced adverse events. LV myocardial deformation
      was significantly decreased in MI patients compared to controls and closely
      related to the infarct size. The GRS, GCS and GLS were all significant predictors
      of adverse cardiac events. In particular, a GLS > -14.1% was independently
      associated with a > 5-fold increased risk for adverse events, even after
      adjustment for the LV ejection fraction and infarct size. CONCLUSIONS: TT-CMR
      derived LV strain is significantly related to the infarct size and adverse
      events. GLS measurement provides strong prognostic information in MI patients.
      KEY POINTS: * TT-CMR provides reliable quantification of LV strain in MI
      patients. * TT-CMR allows prediction of the infarct size and adverse events. * In
      particular, GLS by TT-CMR had independent prognostic value in MI patients.

PMID- 29450718
TI  - ADC as a useful diagnostic tool for differentiating benign and malignant
      vertebral bone marrow lesions and compression fractures: a systematic review and
      meta-analysis.
AB  - OBJECTIVES: To assess the sensitivity and specificity of quantitative assessment
      of the apparent diffusion coefficient (ADC) for differentiating benign and
      malignant vertebral bone marrow lesions (BMLs) and compression fractures (CFs)
      METHODS: An electronic literature search of MEDLINE and EMBASE was conducted.
      Bivariate modelling and hierarchical summary receiver operating characteristic
      modelling were performed to evaluate the diagnostic performance of ADC for
      differentiating vertebral BMLs. Subgroup analysis was performed for
      differentiating benign and malignant vertebral CFs. Meta-regression analyses
      according to subject, study and diffusion-weighted imaging (DWI) characteristics
      were performed. RESULTS: Twelve eligible studies (748 lesions, 661 patients) were
      included. The ADC exhibited a pooled sensitivity of 0.89 (95% confidence interval
      [CI] 0.80-0.94) and a pooled specificity of 0.87 (95% CI 0.78-0.93) for
      differentiating benign and malignant vertebral BMLs. In addition, the pooled
      sensitivity and specificity for differentiating benign and malignant CFs were
      0.92 (95% CI 0.82-0.97) and 0.91 (95% CI 0.87-0.94), respectively. In the meta
      regression analysis, the DWI slice thickness was a significant factor affecting
      heterogeneity (p < 0.01); thinner slice thickness (< 5 mm) showed higher
      specificity (95%) than thicker slice thickness (81%). CONCLUSIONS: Quantitative
      assessment of ADC is a useful diagnostic tool for differentiating benign and
      malignant vertebral BMLs and CFs. KEY POINTS: * Quantitative assessment of ADC is
      useful in differentiating vertebral BMLs. * Quantitative ADC assessment for BMLs
      had sensitivity of 89%, specificity of 87%. * Quantitative ADC assessment for CFs
      had sensitivity of 92%, specificity of 91%. * The specificity is highest (95%)
      with thinner (< 5 mm) DWI slice thickness.

PMID- 29450719
TI  - Coronary plaque characteristics on baseline CT predict the need for late
      revascularization in symptomatic patients after percutaneous intervention.
AB  - OBJECTIVES: To assess pre-procedural plaque characteristics as determined by
      coronary CT angiography (CCTA) and their associations with late revascularization
      in symptomatic post-procedural patients. METHODS: Symptomatic patients with pre
      procedural CCTA were prospectively enrolled and referred for invasive coronary
      angiography (ICA). Plaque characterization was performed on the basis of baseline
      CCTA data. Multivariate logistic regression analysis with a stepwise selection
      method was performed to identify independent predictors of late
      revascularization. RESULTS: Seventy-eight patients with 134 lesions were
      included. Late revascularization was performed to treat 15 ISRs and 22 de novo
      lesions. Lesions with late revascularization showed higher prevalence rates of
      low-attenuation plaque (LAP) and positive remodelling (PR) (70.3% vs. 23.7% and
      86.5% vs. 30.9%; both p < 0.001) at baseline CCTA. However, the incidence of
      spotty calcification or napkin-ring sign (NRS) was not significantly different
      between the subgroups. According to ROC curve analysis, PR and LAP showed the
      largest AUC values for diagnosing lesions with late revascularization (AUC = 0.78
      and 0.73, both p < 0.001). In multivariate analysis, LAP and PR (odds ratio =
      6.30 and 13.94; both p < 0.05) were revealed to be independent predictors for
      late revascularization. CONCLUSIONS: LAP and PR observed by baseline CCTA
      independently predict late revascularization caused by ISR or progression of de
      novo lesions. KEY POINTS: * LAP and PR observed by baseline CT are predictors of
      late revascularization. * NRS and spotty calcification are not associated with
      late revascularization. * CT plaque characterization is useful in identifying
      lesions at high risk of late revascularization.

PMID- 29450721
TI  - Analysis of changes in thermal growing season indices (tGSI) and their relations
      with some selected atmospheric teleconnection patterns (ATPs) over the northwest
      of Iran.
AB  - The daily minimum air temperature data from 18 stations located in the northwest
      of Iran during the period 1986-2015 was used to analyse the inter-annual
      variations and trends of thermal growing season indices (tGSI) and their
      relations with different atmospheric teleconnection patterns (ATPs). To analyze
      the changes in tGSI, tGSS (thermal growing season start), tGSE (thermal growing
      season end), and tGSL, the time period between tGSS and tGSE were considered.
      Using non-parametric Mann-Kendall and Spearman tests, the existence of a
      significant trend for time series of the tGSI and the correlation between ATPs
      and tGSI was evaluated. For eliminating the effect of serial correlation on test
      results, the trend-free pre-whitening approach was applied. Furthermore, residual
      bootstrap method was used to estimate the standard deviation of the Spearman
      correlation coefficient between tGSI and ATPs. The climate-based results showed
      the maximum tGSL increase (13.3 days per decade) for SA-C-M climate. For SH-K-W
      climate, the maximum significant trends for tGSS and tGSE were 9.6 (earlier
      start) and 10.8 (delay) days per decade, respectively. In general, in all
      statistically significant cases, the main cause of the extended tGSL was both
      earlier tGSS and delayed tGSE. In regional scale, it was found that the most
      effective teleconnection pattern on tGSS and tGSE are MEI (positive correlation),
      occurring during late winter and spring, and PDO index (negative correlation) in
      the summer, respectively. Moreover, the tGSL demonstrated the highest correlation
      (negative) with PDO with 1-month delay. The findings highlight that the inter
      annual variations of tGSI in northwest of Iran can be attributed to the influence
      of certain atmospheric teleconnection patterns such as MEI, PDO, NAO, AO, EA, and
      AMO.

PMID- 29450720
TI  - Diabetic Kidney Disease: Is There a Role for Glycemic Variability?
AB  - PURPOSE OF REVIEW: Diabetes is the leading cause of kidney disease globally.
      Diabetic kidney disease (DKD) is a heterogeneous disorder manifested as
      albuminuria and/or decreasing GFR. Hyperglycemic burden is the major contributor
      to the development of DKD. In this article, we review the evidence for the
      contribution of glycemic variability and the pitfalls associated with use of
      hemoglobin A1c (A1C), the gold standard for assessment of glucose control, in the
      setting of DKD. RECENT FINDINGS: Glycemic variability, characterized by swings in
      blood glucose levels, can result in generation of mitochondrial reactive oxygen
      species, a putative inciting factor for hyperglycemia-induced alterations in
      intracellular metabolic pathways. While there is indirect evidence supporting the
      role of glycemic variability in the pathogenesis of DKD, definitive data are
      lacking. A1C has many limitations and is a particularly suboptimal measure in
      patients with kidney disease, because its accuracy is compromised by variables
      affecting RBC survival and other factors. Continuous glucose monitoring (CGM)
      technology has the potential to enable us to use glucose as a more important
      clinical tool, for a more definitive understanding of glucose variability and its
      role in DKD. Glycemic variability may be a factor in the development of DKD, but
      definitive evidence is lacking. Currently, all available glycemic biomarkers,
      including A1C, have limitations and in the setting of DKD and should be used
      cautiously. Emerging data suggest that personal and professional CGM will play an
      important role in managing diabetes in patients with DKD, where risk of
      hypoglycemia is high.

PMID- 29450723
TI  - Molecular imaging and theranostic approaches in pheochromocytoma and
      paraganglioma.
AB  - Pheochromocytomas and their extra-adrenal counterpart paragangliomas (PGLs;
      together called PPGLs), belong to the family of neural crest-derived tumors.
      Given the overexpression of a wide variety of specific targets in PPGLs, it seems
      that these tumors are optimally suited to be imaged by specific
      radiopharmaceuticals. Thus, theranostics approaches with somatostatin agonists
      and antagonists are rapidly evolving in the setting of these tumors and may be
      considered as the next step in the therapeutic arsenal of metastatic PPGLs.

PMID- 29450722
TI  - Incidence and characteristics of chronic thromboembolic pulmonary hypertension in
      Germany.
AB  - BACKGROUND: The incidence of chronic thromboembolic pulmonary hypertension
      (CTEPH) is unknown. Previous studies from the United Kingdom and Spain have
      reported incidence rates of 1.75 and 0.9 per million, respectively. These
      figures, however, may underestimate the true incidence of CTEPH. METHODS: We
      prospectively enrolled patients newly diagnosed with CTEPH within 2016 in
      Germany. Data were obtained from the three German referral centers and from the
      German branch of COMPERA, a European pulmonary hypertension registry. The CTEPH
      incidence was calculated based on German population data, and patient
      characteristics and treatment patterns were described. RESULTS: A total of 392
      patients were newly diagnosed with CTEPH within 2016 in Germany, yielding an
      incidence of 5.7 new cases per million adults. The (mean +/- standard deviation)
      age was 63.5 +/- 15.0 years; males and females were equally affected; 76.3% of
      the patients had a history of venous thromboembolism. A total of 197 (50.3%)
      patients underwent pulmonary endarterectomy. Almost all non-operated patients
      received targeted drug therapy, and 49 patients (25.1% of the non-operated
      patients) were treated with balloon pulmonary angioplasty. CONCLUSION: The
      incidence of CTEPH in Germany 2016 was 5.7 per million adults and thus higher
      than previously reported from other countries. Half of the patients were operated
      while the remaining patients received medical or interventional therapies.
      CLINICAL TRIALS REGISTRATION: http://www.clinicaltrials.gov NCT02660463 and
      NCT01347216.

PMID- 29450724
TI  - Chromaffin cell biology: inferences from The Cancer Genome Atlas.
AB  - Pheochromocytomas and paragangliomas (PCC/PGLs) are rare neuroendocrine tumors
      that are unusually diverse in metabolic profiles, in classes of molecular
      alterations and across a large number of altered genes. The Cancer Genome Atlas
      (TCGA) comprehensively profiled the molecular landscape of PCC/PGLs and
      identified novel genomic alterations and a new molecular classification of
      PCC/PGLs. In this review, we discuss the significant clinico-molecular findings
      of this integrated profiling study. We then review the molecular data of the TCGA
      cohort centering around known markers of sympathoadrenal cell lineage to better
      understand chromaffin cell biology. This analysis adds a new layer, that of
      chromaffin cell type, onto the published molecular classifications and in doing
      so provides inferences about underlying chromaffin cell biology and diversity.

PMID- 29450725
TI  - BDNF effects on dendritic spine morphology and hippocampal function.
AB  - Neurotrophins, including brain-derived neurotrophic factor (BDNF), are expressed
      in the hippocampus, as well as their precursors, the pro-neurotrophins. The
      neurotrophins signal through specific tyrosine kinase receptors and the low
      affinity receptor p75NTR. Moreover, the pro-neurotrophins are considered to be
      biologically active by signaling through specific receptors. The neurotrophins,
      especially BDNF, are involved in processes related to learning and memory.
      Furthermore, it is thought that BDNF also plays a crucial role in major
      depression. This points to a role of BDNF as a central regulator of neuronal
      plasticity within the postnatal hippocampus. Morphological correlates of neuronal
      plasticity are changes on the level of the dendritic spines and, at least in the
      dentate gyrus of the hippocampus, on the level of adult neurogenesis. Specific
      changes in dendritic spines as well as in adult hippocampal neurogenesis can be
      seen in the context of several forms of learning and memory, and it is known that
      depression is accompanied by declines in the rate of adult neurogenesis and in
      spine densities. The possible roles of BDNF in neuronal plasticity within the
      hippocampus are highlighted in this review by focusing on the morphological
      components of neuronal plasticity.

PMID- 29450726
TI  - C9orf72-associated neurodegeneration in ALS-FTD: breaking new ground in ribosomal
      RNA and nucleolar dysfunction.
AB  - Amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) are
      neurodegenerative diseases with distinct clinical appearance. However, both share
      as major genetic risk factor a C9orf72 locus intronic hexanucleotide expansion.
      The pathogenic pathways associated with the expansion-dependent neuronal toxicity
      are still poorly understood. Recent efforts to identify common threads of
      neuronal dysfunction have pointed towards deficits of ribosomal RNA (rRNA)
      biogenesis and loss of nucleolar integrity, a condition known as nucleolar stress
      that is an emerging shared feature among neurodegenerative diseases.
      Intriguingly, the C9orf72 mutation in ALS-FTD interferes with the function of the
      nucleolus by transcripts and dipeptide repeats (DPRs) produced by the
      hexanucleotide expansion. Experimental discrepancies have given rise to different
      hypotheses with regard to the connection of C9orf72 and nucleolar activity. In
      this review, we present and discuss emerging concepts concerning the impact of
      C9orf72 expansion on nucleolar biology. Moreover, we discuss the "nucleolar
      stress hypothesis," according to which nucleolar malfunction accompanies,
      exacerbates, or potentially triggers a degenerative phenotype. Upcoming awareness
      of the involvement of nucleolar stress in C9orf72 ALS-FTD could shed light into
      its pathogenesis, enabling potential treatment options aimed at shielding an
      "Achilles' heel" of neurons.

PMID- 29450728
TI  - Winter vitamin D3 supplementation does not increase muscle strength, but
      modulates the IGF-axis in young children.
AB  - PURPOSE: To explore whether muscle strength, the insulin-like growth factor axis
      (IGF-axis), height, and body composition were associated with serum 25
      hydroxyvitamin D [25(OH)D] and affected by winter vitamin D supplementation in
      healthy children, and furthermore to explore potential sex differences. METHODS:
      We performed a double-blind, placebo-controlled, dose-response winter trial at
      55oN. A total of 117 children aged 4-8 years were randomly assigned to either
      placebo, 10, or 20 ug/day of vitamin D3 for 20 weeks. At baseline and endpoint,
      we measured muscle strength with handgrip dynamometer, fat mass index (FMI), fat
      free mass index (FFMI), height, plasma IGF-1, IGF-binding protein 3 (IGFBP-3),
      and serum 25(OH)D. RESULTS: At baseline, serum 25(OH)D was positively associated
      with muscle strength, FFMI, and IGFBP-3 in girls only (all p < 0.01). At
      endpoint, baseline-adjusted muscle strength, FMI and FFMI did not differ between
      intervention groups. However, baseline-adjusted IGF-1 and IGFBP-3 were higher
      after 20 ug/day compared to placebo (p = 0.043 and p = 0.006, respectively) and
      IGFBP-3 was also higher after 20 ug/day compared to 10 ug/day (p = 0.011).
      Children tended to be taller after 20 ug/day compared to placebo (p = 0.064). No
      sex interactions were seen at endpoint. CONCLUSIONS: Avoiding the winter-related
      decline in serum 25(OH)D may influence IGF-1 and IGFBP-3 in children. Larger
      trials are required to confirm these effects, and the long-term implication for
      linear growth.

PMID- 29450729
TI  - Physical activity and Mediterranean diet based on olive tree phenolic compounds
      from two different geographical areas have protective effects on early
      osteoarthritis, muscle atrophy and hepatic steatosis.
AB  - PURPOSE: Osteoarthitis (OA) leads to progressive loss of articular cartilage,
      pain and joint disability. An acute injury constitutes an important risk factor
      for early OA, determining an inflammatory process responsible of cartilage
      degeneration and muscle atrophy, due to the joint pain and immobility. The study
      aims to assess the effects of conjugation of physical activity and diet enriched
      by olive tree compounds [extra virgin olive oil (EVOO) and olive leaf extract
      (OLE)], on the musculoskeletal system in OA rat model. METHODS: OA was induced by
      anterior cruciate ligament transection and confirmed by Mankin and OARSI scores.
      Rats were subjected to physical activity on treadmill 5 days a week for 10 min
      daily and fed with experimental diets (standard diet enriched with Sicilian EVOO,
      Tunisian EVOO and Tunisian EVOO-OLE) for 12 weeks. Immunohistochemistry was used
      to evaluate IL-6 and lubricin expression in cartilage tissue and ELISA was used
      to quantify these proteins in serum at different time points. Histology and
      histomorphometry analysis were done to valuate liver steatosis, muscle atrophy
      and cartilage pathological changes. RESULTS: Compared to the OA group, the
      experimental groups showed general increased lubricin and decreased IL-6
      expression, significant muscle hypertrophy and no signs of liver steatosis,
      suggesting the beneficial effects of physical activity coupled with EVOO-enriched
      diets on rat articular cartilage. Interestingly, the best result was shown for
      Sicilian EVOO-enriched diet. CONCLUSION: In conclusion, the conjugation of
      physical activity and EVOO-enriched diet determines a significant articular
      cartilage recovery process in early OA.

PMID- 29450727
TI  - Metabolic implications of hypoxia and pseudohypoxia in pheochromocytoma and
      paraganglioma.
AB  - Hypoxia is a critical driver of cancer pathogenesis, directly inducing malignant
      phenotypes such as epithelial-mesenchymal transition, stem cell-like
      characteristics and metabolic transformation. However, hypoxia-associated
      phenotypes are often observed in cancer in the absence of hypoxia, a phenotype
      known as pseudohypoxia, which is very well documented in specific tumour types,
      including in paraganglioma/pheochromocytoma (PPGL). Approximately 40% of the PPGL
      tumours carry a germ line mutation in one of a number of susceptibility genes of
      which those that are found in succinate dehydrogenase (SDH) or in von Hippel
      Lindau (VHL) genes manifest a strong pseudohypoxic phenotype. Mutations in SDH
      are oncogenic, forming tumours in a select subset of tissues, but the cause for
      this remains elusive. Although elevated succinate levels lead to increase in
      hypoxia-like signalling, there are other phenotypes that are being increasingly
      recognised in SDH-mutated PPGL, such as DNA hypermethylation. Further, recently
      unveiled changes in metabolic re-wiring of SDH-deficient cells might help to
      decipher cancer related roles of SDH in the future. In this review, we will
      discuss the various implications that the malfunctioning SDH can have and its
      impact on cancer development.

PMID- 29450730
TI  - Herpes simplex encephalitis relapse associated with positive N-methyl-D-aspartate
      receptor antibodies.

PMID- 29450731
TI  - Is mini-percutaneous nephrolithotomy a safe alternative to extracorporeal
      shockwave lithotripsy in pediatric age group in borderline stones? a randomized
      prospective study.
AB  - PURPOSE: The extracorporeal shockwave lithotripsy (ESWL) remains the most common
      first line of treatment for renal stones in the pediatric population. The purpose
      of this study is to evaluate and compare the outcomes of the ESWL and mini
      percutaneous nephrolithotomy (mini-PCNL). PATIENTS AND METHODS: A total of 108
      patients younger than 12 years of age with 1-2 cm single renal stone (pelvic or
      calyceal) were randomized into two groups, each containing 54 patients. Patients
      in group A were subjected to mini-PCNL using 16.5 Fr percutaneous sheath while
      those in group B underwent ESWL using Dornier Compact Sigma. RESULTS: The stone
      free rate (SFR) after first session was 88.9% (48 cases) and 55.6% (30 cases) for
      groups A and B, respectively. The difference is highly statistically significant
      P = 0.006. Two patients (3.7%) in group A needed 2nd session of PCNL, while 18
      patients (33.3%)in group B needed a 2nd session, of theses 18 patients six
      patients needed a 3rd session of ESWL. After the third session of ESWL and second
      look PCNL the stone-free rates were 92.59% (50 cases) and 88.89% (48 cases) for
      groups A and B, respectively, (P = 0.639), which is statistically insignificant.
      The mean hospital stay and fluoroscopy exposure were significantly longer in the
      mini-PCNL group. The complication rate in groups A and group B were (22.2%) and
      (14.8%), respectively, which is statistically insignificant (P = 0.484).
      CONCLUSIONS: According to Clavien grade of complications mini-PCNL is a safe
      procedure, and after three session of ESWL, mini-PCNL has a similar stone-free
      rate with a lower retreatment rate. However, the mini-PCNL has more radiation
      exposure, and requires a longer hospital stay.

PMID- 29450732
TI  - Combined prostatic urethral lift and remodeling of the prostate and bladder neck:
      a modified transurethral approach in the treatment of symptomatic lower urinary
      tract obstruction.
AB  - PURPOSE: The aim of the study was to evaluate the feasibility and safety of
      combining prostatic urethral lift (PUL) and a limited resection of the prostatic
      middle lobe or bladder neck incision in the treatment of lower urinary tract
      symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). METHODS: Twenty
      eight patients were treated at two tertiary centers and followed prospectively.
      Patient evaluations included patient characteristics, relief of LUTS symptoms,
      erectile and ejaculatory function, continence, operative time and adverse events.
      Patients were followed for a mean of 10.9 months. RESULTS: Patient
      characteristics were as follows: age 66 years (46-85), prostate volume 39.6 cc
      (22-66), preoperative IPSS/AUASI 20 (6-35)/QoL 3.9 (1-6)/peak flow 10.5 mL/s (4.0
      19)/post-void residual volume (PVR) 123 mL (0-500). Mean operating time was 31
      min (9-55). Postoperative complications were minor except for the surgical
      retreatment of one patient for blood clot retention (Clavien 3b). One patient
      required catheterization due to urinary retention. Reduction of symptoms (IPSS -
      59.6%), increase in QoL (+ 49.0%), increase in flow (+ 111.5%), and reduction of
      PVR (- 66.8%) were significant. Antegrade ejaculation was always maintained.
      CONCLUSION: Our data suggest that a combination of PUL and transurethral surgical
      techniques is feasible, safe, and effective. This approach may be offered to
      patients with moderate size prostates including those with unfavorable anatomic
      conditions for PUL. This procedure is still 'minimally invasive' and preserves
      sexual function. In addition, it may add to a higher functional efficacy compared
      to PUL alone. STUDY REGISTER NUMBER: DRKS00008970.

PMID- 29450733
TI  - Miniaturised percutaneous nephrolithotomy versus flexible ureteropyeloscopy: a
      systematic review and meta-analysis comparing clinical efficacy and safety
      profile.
AB  - PURPOSE: This study aims to comparatively evaluate clinical outcomes of mini-PCNL
      and FURS for treating urinary tract calculi in a single session. METHODS: A
      systematic search using electronic databases was performed for studies comparing
      mini-PCNL and FURS for the treatment of urinary tract calculi. The primary
      outcome measurements were stone-free rates (SFRs) and complication rates for both
      techniques. Secondary outcome measurements were to compare patient demographics,
      operative duration, and inpatient stay. Meta-analysis was performed with Review
      Manager version 5.3 software. RESULTS: Sixteen studies on 1598 patients (n = 877
      for mini-PCNL and n = 721 for FURS) met inclusion criteria. Demographics
      including age (p = 0.26), body mass index (BMI) (p = 0.51), and gender ratio (p =
      0.6), were similar in both groups. Overall, SFR was significantly greater in the
      mini-PCNL group compared to the FURS group (n = 763/877, 89.3 +/- 8.4% versus n =
      559/721, 80.1 +/- 13.3% [OR 2.01; 95% CI 1.53-2.64; p < 0.01]). Duration of
      inpatient stay was significantly greater in the mini-PCNL group compared to the
      FURS group (n = 877, 4 +/- 1.6 days versus n = 721, 2.5 +/- 2.2 days,
      respectively [WMD: 1.77; 95% CI 1.16-2.38, p < 0.01]. Overall complication rates
      were not significantly different between mini-PCNL and FURS (n = 171/877, 19.5 +/
      19.1% versus n = 112/721, 15.5 +/- 18.9%, respectively [OR 1.43; 95% CI 0.85
      2.4, p = 0.18]). CONCLUSIONS: Mini-PCNL is associated with greater SFRs and
      longer inpatient stay compared to FURS. Complication rates were similar for both
      techniques. The advantages and disadvantages of both technologies should be
      familiar to urologists and conveyed to patients prior to urological intervention
      for nephrolithiasis.

PMID- 29450734
TI  - Two-hour post-challenge glucose is a better predictor of adverse outcome after
      myocardial infarction than fasting or admission glucose in patients without
      diabetes.
AB  - AIMS: We evaluate prevalence of new abnormal glucose tolerance (AGT) in post-MI
      survivors without known diabetes (DM) if guidelines are followed and compare the
      ability of admission (APG), fasting (FPG) and 2-h post-load plasma glucose (2h
      PG) to predict prognosis. METHODS: A total of 674 patients were followed up for 4
      years for incidence of major adverse cardiovascular events (MACE) of
      cardiovascular death, non-fatal re-infarction or non-haemorrhagic stroke. Ability
      of models including APG, FPG and 2h-PG to predict MACE was compared. RESULTS: Of
      the total, 93-96% of impaired glucose tolerance and 64-75% of DM would be missed
      with current guidelines. MACE was higher in the upper quartiles of 2h-PG. When 2h
      PG and FPG were included simultaneously in models, only 2h-PG predicted MACE (HR
      1.12, CI 1.04-1.20, p = 0.0012), all cause mortality (HR 1.17, CI 1.05-1.30, p =
      0.0039), cardiovascular mortality (HR 1.17, CI 1.02-1.33, p = 0.0205) and non
      fatal MI (HR 1.10, CI 1.01-1.20, p = 0.0291). Adding 2h-PG significantly improved
      ability of models including FPG (chi2 = 16.01, df = 1, p = 0.0001) or FPG and APG
      (chi2 = 17.36, df = 1, p = 0.000) to predict MACE. Model including 2h-PG only had
      the lowest Akaike's information criteria and highest Akaike weights suggesting
      that this was the best in predicting events. Adding 2h-PG to models including FPG
      or APG with other co-variates yielded continuous net reclassification improvement
      (NRI) of 0.22 (p = 0.026) and 0.27 (p = 0.005) and categorical NRI of 0.09 (p =
      0.032) and 0.12 (p = 0.014), respectively. Adding 2 h-PG to models including only
      FPG, only APG and both yielded integrated discrimination improvement of 0.012 (p
      = 0.015), 0.022 (p = 0.001) and 0.013 (p = 0.014), respectively. CONCLUSIONS: AGT
      is under-diagnosed on current guidelines. 2h-PG is a better predictor of
      prognosis compared to APG and FPG.

PMID- 29450736
TI  - Health and quality of life differ between community living older people with and
      without remaining teeth who recently received formal home care: a cross sectional
      study.
AB  - OBJECTIVE: To assess oral health, health, and quality of life (QoL) of care
      dependent community-living older people with and without remaining teeth who
      recently received formal home care. MATERIALS AND METHODS: For this cross
      sectional observational study, community-living older people (>= 65 years), who
      recently (< 6 months) received formal home care, were interviewed with validated
      questionnaires and underwent an oral examination. Oral health, general health,
      medicines usage, frailty (Groningen Frailty Indicator), cognition (Minimal Mental
      State Examination), QoL (RAND 36), and oral health-related QoL (Oral Health
      Impact Profile-14) were assessed. RESULTS: One hundred three out of 275
      consecutive eligible older people (median age 79 [IQR (Inter Quartile Range) 72
      85 years] participated in the study. Thirty-nine patients had remaining teeth and
      64 were edentulous. Compared with edentulous older people, older people with
      remaining teeth scored significantly better on frailty, QoL, physical
      functioning, and general health. No significant differences were seen in
      cognition. Dental and periodontal problems were seen in more than half of the
      patients with remaining teeth. Two third of the edentulous patients did not visit
      their dentist regularly or at all. CONCLUSIONS: Care-dependent home-dwelling
      older people with remaining teeth generally were less frail, scored better on
      physical functioning and general health and had better QoL than edentulous older
      people. Dental and periodontal problems were seen in approximately 50% of the
      elderly. CLINICAL RELEVANCE: Notwithstanding their common dental problems,
      frailty, health, and QoL are better in home-dwelling older people with remaining
      teeth. To maintain this status, we advise not only dentists, but also health care
      workers and governments, to encourage people to maintain good oral health.

PMID- 29450735
TI  - N-acetyl-L-cysteine protects dental tissue stem cells against oxidative stress in
      vitro.
AB  - OBJECTIVES: The aim of our study was to investigate whether N-acetyl-L-cysteine
      (NAC) could protect stem cells from exfoliated deciduous teeth (SHED) against
      oxidative damage, during in vitro cultivation, to preserve regenerative potential
      of these cells. Accordingly, we examined the potential of cell culture
      supplementation with NAC in prevention of lipid peroxidation, unfavorable changes
      of total lipids fatty acid composition, and the effects on the activity of
      antioxidant enzymes. MATERIAL AND METHODS: We analyzed the extent of oxidative
      damage in SHED after 48 h treatment with different NAC concentrations. Cellular
      lipid peroxidation was determined upon reaction with thiobarbituric acid. All
      enzyme activities were measured spectrophotometrically, based on published
      methods. Fatty acid methyl esters were analyzed by gas-liquid chromatography.
      RESULTS: Concentration of 0.1 mM NAC showed the most profound effects on SHED,
      significantly decreasing levels of lipid peroxidation in comparison to control.
      This dose also diminished the activities of antioxidant enzymes. Furthermore, NAC
      treatment significantly changed fatty acid composition of cells, reducing levels
      of oleic acid and monounsaturated fatty acids and increasing linoleic acid, n-6,
      and total polyunsaturated fatty acid (PUFA) proportions. CONCLUSION: Low dose of
      NAC significantly decreased lipid peroxidation and altered fatty acid composition
      towards increasing PUFA. The reduced oxidative damage of cellular lipids could be
      strongly related to improved SHED survival in vitro. CLINICAL RELEVANCE: Low
      doses of antioxidants, applied during stem cells culturing and maintenance, could
      improve cellular characteristics in vitro. This is prerequisite for successful
      use of stem cells in various clinical applications.

PMID- 29450737
TI  - Correlation between plaque control and gingival health using short and extended
      oral hygiene intervals.
AB  - OBJECTIVES: To evaluate the correlation between dental plaque formation and
      gingival health in subjects performing high oral hygiene standards over short or
      extended intervals. MATERIALS AND METHODS: Fifty-two non-dental students
      volunteered for this study. The subjects, trained to perform high oral hygiene
      standards, were randomized to perform oral hygiene at 12-, 24-, 48-, or 72-h
      interval over 30 days. The plaque index (PlI) and the gingival index (GI) were
      evaluated at baseline, 15, and 30 days. For the statistical analysis, oral
      hygiene intervals were collapsed into daily (12 and 24 h; G12/24) and extended
      (48 and 72 h; G48/72) intervals. Summary statistics (mean +/- SD) and Spearman
      correlations between the PlI and the GI at baseline, 15, and 30 days were
      estimated. RESULTS: At baseline, correlation coefficients between PlI and GI were
      positive for both groups (r = 0.29 and r = 0.25). At day 15 and 30, correlation
      was maintained with similar baseline values for the G48/72 group. GI levels did
      not increase despite an increase in PlI for the G12/24 group, and the correlation
      was lower than that observed at baseline (r = 0.13 vs. r = 0.29). CONCLUSIONS: In
      subjects with high oral hygiene standards, the oral hygiene frequency governs the
      correlation between dental plaque formation and gingival health. Subjects
      performing high oral hygiene standards at daily intervals will maintain gingival
      health in difference to subjects using extended hygiene intervals. CLINICAL
      RELEVANCE: Subjects performing high oral hygiene standards at daily intervals
      will maintain gingival health in difference to subjects using extended hygiene
      intervals.

PMID- 29450738
TI  - Double-blind, randomized controlled clinical trial on analgesic efficacy of local
      anesthetics articaine and bupivacaine after impacted third molar extraction.
AB  - OBJECTIVE: The objective of this randomized controlled clinical trial (RCT) was
      to compare the effect of bupivacaine and articaine at habitual doses on pain
      intensity and the need for analgesics after lower third molar extraction.
      MATERIALS AND METHODS: The final study sample comprised 50 Caucasian volunteers
      (26 males and 24 females; age range, 18-30 years) undergoing scheduled surgical
      extraction of impacted lower third molar. A computer-generated random sequence
      was used to allocate participants to the articaine (4%) or bupivacaine (0.5%)
      group. Surgeons and patients were blinded by labeling the articaine and
      bupivacaine carpules with numbers (1 and 2, respectively). Postoperative pain
      intensity (primary outcome) was evaluated with a visual analogue scale (VAS),
      while the requirement for and timing of rescue medication and the quality of
      intraoperative anesthesia were also measured (secondary outcomes). RESULTS: VAS
      measured pain intensity was significantly higher (p < 0.05) in the articaine
      group than in the bupivacaine group at all time points except for 8 h post
      surgery (p = 0.052). Rescue medication was required by 13 (52%) patients in the
      articaine group and 8 (32%) patients in the bupivacaine group, although the
      difference did not reach statistical significance (p = 0.252). The groups did not
      significantly differ (p = 0.391) in the quality of the intraoperative anesthesia.
      CONCLUSIONS: Bupivacaine is a valid alternative to articaine in third molar
      surgery and may offer residual anesthesia as a means of reducing postoperative
      pain. However, further well-designed RCTs are required in larger study
      populations to verify the effectiveness of bupivacaine to achieve residual
      analgesia after oral surgery. CLINICAL RELEVANCE: These findings suggest that
      bupivacaine may be useful as a coadjuvant to control acute postoperative pain.
      TRIAL REGISTRATION: ACTRN12617001138370.

PMID- 29450739
TI  - Influence of operator skill level on the clinical outcome of non-surgical
      periodontal treatment: a retrospective study.
AB  - OBJECTIVES: The aim of this study is to evaluate the effect of operators
      experience and skill on treatment results of initial non-surgical periodontal
      therapy. MATERIALS AND METHODS: Initial periodontal treatment was carried out by
      either second-year periodontal residents (PR) or last year dental students (DS).
      From the treatment records of patients in each group, plaque and bleeding
      indices, and pocket depth (PD) at baseline and at re-evaluation were collected
      retrospectively on each tooth at six locations. Data were separated according to
      tooth type, area, and probing depth categories, sub-grouped to 1-3, 4-5, and >= 6
      mm. RESULTS: Fifty and 49 records of DS and PR patients, accordingly, were
      analyzed. Initial periodontal treatment improved patient compliance in both
      groups and reduced signs of inflammation with significantly superior results in
      the PR group. Significant change in percentage of pockets was recorded in each
      category. The increase in percentage of sites with PD 1-3 mm and decrease in
      percentage of PD >= 6 mm pockets was significantly (p <= 0.001) superior in
      patients treated by PR. Percentage of 4-5 mm pockets was significantly reduced in
      both groups (p <= 0.01), with a significantly greater reduction in the mandibular
      molar and anterior teeth in the PR group. CONCLUSIONS: Experience and skill
      significantly affect the outcome of non-surgical periodontal therapy, with more
      positive improvement in patient compliance and clinical parameters when performed
      by a more qualified operator. CLINICAL RELEVANCE: Improvement of operator skills
      may decrease the number of residual pockets and increase patient compliance
      following non-surgical periodontal treatment.

PMID- 29450740
TI  - Perfluorocarbon induces alveolar epithelial cell response through structural and
      mechanical remodeling.
AB  - During total liquid ventilation, lung cells are exposed to perfluorocarbon (PFC)
      whose chemophysical properties highly differ from standard aqueous cell feeding
      medium (DMEM). We herein perform a systematic study of structural and mechanical
      properties of A549 alveolar epithelial cells in order to characterize their
      response to PFC exposure, using DMEM as control condition. Changes in F-actin
      structure, focal adhesion density and glycocalyx distribution are evaluated by
      confocal fluorescent microscopy. Changes in cell mechanics and adhesion are
      measured by multiscale magnetic twisting cytometry (MTC). Two different
      microrheological models (single Voigt and power law) are used to analyze the cell
      mechanics characterized by cytoskeleton (CSK) stiffness and characteristic
      relaxation times. Cell-matrix adhesion is analyzed using a stochastic multibond
      deadhesion model taking into account the non-reversible character of the cell
      response, allowing us to quantify the adhesion weakness and the number of
      associated bonds. The roles of F-actin structure and glycocalyx layer are
      evaluated by depolymerizing F-actin and degrading glycocalyx, respectively.
      Results show that PFC exposure consistently induces F-actin remodeling, CSK
      softening and adhesion weakening. These results demonstrate that PFC triggers an
      alveolar epithelial cell response herein evidenced by a decay in intracellular
      CSK tension, an adhesion weakening and a glycocalyx layer redistribution. These
      PFC-induced cell adjustments are consistent with the hypothesis that cells
      respond to a decrease in adhesion energy at cell surface. This adhesion energy
      can be even further reduced in the presence of surfactant adsorbed at the cell
      surface.

PMID- 29450741
TI  - Utility of cardiac computed tomography scanning in the diagnosis and pre
      operative evaluation of patients with infective endocarditis.
AB  - Transesophageal echocardiography (TEE) is the gold standard imaging study used in
      the diagnosis of infective endocarditis (IE). Computed tomography angiography
      (CTA) has undergone rapid advancement as a cardiac imaging technique and has
      previously shown promise in small non-randomized studies for evaluation of IE. We
      hypothesized that cardiac CTA would perform similarly to TEE in the detection of
      endocarditic lesions and that there would be no difference in clinical outcomes
      whether the coronary arteries were evaluated by CTA or invasive coronary
      angiography (ICA). 255 adults who underwent surgery for IE at the Mayo Clinic
      Rochester between January 1, 2006 and June 1, 2014 were identified
      retrospectively. 251 patients underwent TEE and 34 patients underwent cardiac
      CTA. TEE had statistically higher detection of vegetations (95.6 vs. 70.0%, p <
      0.0001) and leaflet perforations (81.3 vs. 42.9%, p = 0.02) as compared to
      cardiac CTA. For detection of abscess/pseudoaneurysm TEE had a similar
      sensitivity to cardiac CTA (90.5 vs. 78.4%, p = 0.21). There was no significant
      difference in peri-operative outcomes whether coronary arteries were evaluated by
      CTA or ICA. The greatest advantage of cardiac CT in the setting of IE is its
      ability to couple the detection of complex cardiac anatomic abnormalities with
      coronary artery delineation, serving two important components of the diagnostic
      evaluation, particularly among patients who will require surgical intervention
      due to IE complications. Cardiac CTA may be considered as an alternate coronary
      artery imaging modality in IE patients with low to intermediate risk of disease
      but meet guideline recommendations for coronary artery imaging.

PMID- 29450743
TI  - Construction of a reverse genetic system for porcine astrovirus.
AB  - In order to construct a full-length infectious cDNA clone of porcine astrovirus,
      three fragments covering the complete genome of PAstV1-GX1 strain were amplified
      by RT-PCR. All three PCR-amplified fragments were cloned into T-Vector pMD19
      (Simple), and subsequently assembled into a full-length cDNA clone by subcloning.
      A silent nucleotide change creating a PstI site was engineered into the full
      length cDNA clone to distinguish the rescued virus from the parental virus. Upon
      transfection of BHK-21 cells with the in vitro transcripts of both the original
      and constructed cDNAs, typical cytopathic effects were observed on PK-15 cells
      after serial passaging of the cell supernatant. The construction and recovery of
      the infectious cDNA clone of porcine astrovirus will provide a valuable
      experimental system to study the genome function and pathogenesis of
      astroviruses.

PMID- 29450742
TI  - Focused cardiac ultrasound as a predictor of readmission in acute decompensated
      heart failure.
AB  - Acute decompensated heart failure (ADHF) is a common reason for admission to the
      hospital, and readmission is frequent. Multiple factors contribute to
      rehospitalizations, but inadequate assessment of volume status leading to
      persistent congestion is an important factor. We sought to determine if focused
      cardiac ultrasound (FCU) of the inferior vena cava (IVC), as a surrogate of
      volume status, would predict readmission of ADHF patients after index
      hospitalization. Patients admitted with a primary diagnosis of ADHF were
      prospectively enrolled. All patients underwent FCU of the IVC on admission and
      then daily. 82 patients were enrolled. Patients demonstrated improvement in heart
      failure physical examination findings and symptoms during the hospitalization.
      There was a reduction in the size of the IVC and a significant increase in
      patients with small collapsible vena cava. Logistic regression analysis of
      physical examination, patient symptoms, and IVC parameters at discharge
      demonstrated IVC collapsibility and patient reported dyspnea improvement as the
      only significant variables to predict readmission or emergency department visit.
      FCU assessment of IVC size and collapsibility may be useful in patients with ADHF
      to predict risk of being readmitted within 30 days of hospital discharge.

PMID- 29450744
TI  - High-density lipoprotein (HDL) promotes angiogenesis via S1P3-dependent VEGFR2
      activation.
AB  - High-density lipoprotein (HDL) has previously been shown to promote angiogenesis.
      However, the mechanisms by which HDL enhances the formation of blood vessels
      remain to be defined. To address this, the effects of HDL on the proliferation,
      transwell migration and tube formation of human umbilical vein endothelial cells
      were investigated. By examining the abundance and phosphorylation (i.e.,
      activation) of the vascular endothelial growth factor receptor VEGFR2 and
      modulating the activity of the sphingosine-1 phosphate receptors S1P1-3 and
      VEGFR2, we characterized mechanisms controlling angiogenic responses in response
      to HDL exposure. Here, we report that HDL dose-dependently increased endothelial
      proliferation, migration and tube formation. These events were in association
      with increased VEGFR2 abundance and rapid VEGFR2 phosphorylation at
      Tyr1054/Tyr1059 and Tyr1175 residues in response to HDL. Blockade of VEGFR2
      activation by the VEGFR2 inhibitor SU1498 markedly abrogated the pro-angiogenic
      capacity of HDL. Moreover, the S1P3 inhibitor suramin prevented VEGFR2 expression
      and abolished endothelial migration and tube formation, while the S1P1 agonist
      CYM-5442 and the S1P2 inhibitor JTE-013 had no effect. Last, the role of S1P3 was
      further confirmed in regulation of S1P-induced endothelial proliferation,
      migration and tube formation via up-regulation and activation of VEGFR2.
      Together, these findings argue that HDL promotes angiogenesis via S1P3-dependent
      up-regulation and activation of VEGFR2 and also suggest that the S1P-S1P3-VEGFR2
      signaling cascades as a novel target for HDL-modulating therapy implicated in
      vascular remodeling and functional recovery in atherosclerotic diseases such as
      myocardial infarction and ischemic stroke.

PMID- 29450745
TI  - Clinical Management of Women with Monogenic Diabetes During Pregnancy.
AB  - PURPOSE OF REVIEW: Monogenic diabetes accounts for 1-2% of all diabetes cases,
      but is frequently misdiagnosed as type 1, type 2, or gestational diabetes.
      Accurate genetic diagnosis directs management, such as no pharmacologic treatment
      for GCK-MODY, low-dose sulfonylureas for HNF1A-MODY and HNF4A-MODY, and high-dose
      sulfonylureas for KATP channel-related diabetes. While diabetes treatment is
      defined for the most common causes of monogenic diabetes, pregnancy poses a
      challenge to management. Here, we discuss the key issues in pregnancy affected by
      monogenic diabetes. RECENT FINDINGS: General recommendations for pregnancy
      affected by GCK-MODY determine need for maternal insulin treatment based on fetal
      mutation status. However, a recent study suggests macrosomia and miscarriage
      rates may be increased with this strategy. Recent demonstration of transplacental
      transfer of sulfonylureas also raises questions as to when insulin should be
      initiated in sulfonylurea-responsive forms of monogenic diabetes. Pregnancy
      represents a challenge in management of monogenic diabetes, where factors of
      maternal glycemic control, fetal mutation status, and transplacental transfer of
      medication must all be taken into consideration. Guidelines for pregnancy
      affected by monogenic diabetes will benefit from large, prospective studies to
      better define the need for and timing of initiation of insulin treatment.

PMID- 29450746
TI  - Impact of habitat heterogeneity on zooplankton assembly in a temperate river
      floodplain system.
AB  - Dissimilar life features of Rotifera, Cladocera and Copepoda enable these
      organisms to respond differently to changes in the hydrological regime which
      influence alterations in environmental characteristics. We investigated the
      effect of habitat heterogeneity (e.g. eupotamal, parapotamal, palaeopotamal) on
      individual zooplankton group assemblages and biodiversity indices (alpha, beta
      and gamma diversity) during hydro regime change in floodplain waterbodies.
      Dissolved oxygen and organic nitrogen concentrations changed significantly among
      hydrological states while water depth was affected by both site and hydro regime
      replacement. Each studied site supported different zooplankton assemblage that
      highly depended on species-specific responses to hydro regime change. Also,
      individual zooplankton groups exhibited different correlations with specific
      environmental parameters regarding site change. Throughout the study, rotifers'
      local (alpha) and among-community (beta) diversities were susceptible to the site
      and inundation change while the microcrustacean biodiversity pattern diverged.
      Copepods highly discriminated different habitat types and hydrological phases at
      the regional scale (gamma diversity), while we found a complete lack of
      biodiversity dependence on both site and hydrology for Cladocera. Our results
      show that heterogeneous environments support the development of different
      zooplankton assemblages that express the within-group dissimilarities. They also
      point to the importance of identifying processes in hydrologically variable
      ecosystems that influence biodiversity patterns at an individual zooplankton
      group level. Our results suggest the use of appropriate zooplankton groups as
      biological markers in natural habitats and stress the importance of proper
      management in preserving biodiversity in floodplain areas.

PMID- 29450748
TI  - Water Exchange Versus Split-Dose Bowel Preparation and the ADR: Is WE There Yet?

PMID- 29450747
TI  - Efficacy of Bifidobacterium breve Fermented Milk in Maintaining Remission of
      Ulcerative Colitis.
AB  - BACKGROUND: Fermented milk products containing Bifidobacterium breve strain
      Yakult (BFM) may improve clinical status in ulcerative colitis (UC) patients.
      AIMS: To assess efficacy of BFM in maintaining remission in Japanese patients
      with quiescent UC. METHODS: This double-blind study (B-FLORA) enrolled 195
      patients with quiescent UC, randomized to receive one pack of BFM fermented milk
      per day [Bifidobacterium breve strain Yakult (10 billion bacteria) and
      Lactobacillus acidophilus (1 billion bacteria)] (n = 98) or matching placebo (n =
      97) for 48 weeks. The primary efficacy endpoint was relapse-free survival
      (relapse: rectal bleeding score >= 2 on Sutherland disease activity index scale
      for 3 consecutive days and/or initiation of remission induction therapy for
      worsening of UC). RESULTS: An interim analysis was conducted after inclusion and
      follow-up of one-third of patients for the first phase of the study (n = 195).
      Relapse-free survival was not significantly different between the BFM and placebo
      groups (P = 0.643; hazard ratio 1.16; 95% CI 0.63-2.14, log-rank test), nor was
      the incidence of relapse. Therefore, the study was discontinued for lack of
      efficacy. An exploratory analysis of fecal samples from a subgroup of patients
      revealed no effects of either study beverage on intestinal microbiota, but there
      was a significant decrease in Bifidobacterium species before relapse, regardless
      of treatment group. Three mild adverse events occurred for which a causal
      relationship with the study beverage could not be ruled out (placebo: abdominal
      bloating and stress in one patient; BFM: body odor in one patient). CONCLUSIONS:
      BFM had no effect on time to relapse in UC patients compared with placebo. STUDY
      REGISTRATION: UMIN000007593.

PMID- 29450749
TI  - An Analysis of the Clinical, Laboratory, and Histological Features of Striped,
      Punctate, and Nodular Gastric Antral Vascular Ectasia.
AB  - BACKGROUND: Gastric antral vascular ectasia (GAVE) commonly presents as linear
      striped ("watermelon stomach") or punctate phenotypes, to which a newly
      discovered nodular form was recently added. AIMS: We performed a retrospective
      cohort study to detail and compare the clinical and histological characteristics
      of major GAVE phenotypes. METHODS: In 136 GAVE patients (tertiary care ambulatory
      and inpatient, median age 61.3 years, 73 men, and 63 women), clinical and
      laboratory results were recorded, with comorbidities, endoscopy indications, and
      complications of cirrhosis. In 74 patients, GAVE histopathology was cataloged by
      a pathologist masked to endoscopy results. RESULTS: Median age 61.3 years, 73
      men, and 63 women. GAVE phenotypes were: linear striped-62 (46%), punctate-32
      (24%), and nodular-41 (30%). Endoscopy was commonly performed for variceal
      screening in linear striped (45%) and nodular (34%) GAVE and for gastrointestinal
      bleeding in punctate (41%) and nodular (29%) GAVE, respectively. Of 89 cirrhotic
      patients, 37.5% each had linear striped or nodular GAVE, 24.7% had punctate forms
      (p = 0.03). Child-Turcotte-Pugh and Model for End-Stage Liver Disease scores were
      similar among phenotypes. Histologically, reactive epithelial hyperplasia and
      vascular ectasia were universal; smooth muscle proliferation was more common and
      consistent (78-86%) than microvascular thrombi (27-59%) and fibrohyalinosis (18
      53%), which each varied with phenotype. CONCLUSIONS: Nodular GAVE is a gastric
      mucosal abnormality that is similar to the linear striped and punctate
      phenotypes, yet has distinct clinical and histological features. Increased
      awareness of nodular GAVE by endoscopists is needed to avoid its misdiagnosis as
      nonspecific antral nodules.

PMID- 29450750
TI  - Survival Impact of Stations of Pathological Lymph Nodes in N2 Non-small Cell Lung
      Cancer in a French Hospital.
AB  - BACKGROUND: The prognosis of lung cancer remains poor; only 20% of patients can
      undergo surgery. N2 non-small cell lung cancer (NSCLC) is a heterogeneous
      disease. We conducted a retrospective study to analyze the impact of N2 location
      on survival. METHODS: This study included 342 NSCLC with N2 involvement between
      1988 and 2014. Patient-related data were collected through the CRB biobank and
      included demographic, therapeutic, and survival data. Survival was analyzed
      according to Kaplan-Maier method. Cox's regression analysis and analysis of
      variance (ANOVA) were used to determine factors significantly associated with
      survival. RESULTS: The population average age was 61.6 years; 82.2% were men, a
      majority were former smokers (87.1%), and 45.3% had adenocarcinoma. The main
      prognostic factors were male gender (p = 0.01), number of nodes (p < 0.0001), and
      tumor size (p < 0.0001). N2 disease had a poor survival (16 months) compared with
      N0 (32 months) and N1 (21.1 months) disease (p < 0.0001). The patients with
      involvement of station 4 (survival = 17.8 months) seemed to have a prognosis
      between those with station 7 (survival = 10.5 months) and N1 (survival = 22.6
      months), p = 0.0005. CONCLUSIONS: N2 location has a prognostic impact in
      surgically NSCLC, and station 4 involvement has a better prognostic than station
      7.

PMID- 29450751
TI  - Left Lobe Mobilization Strategy of Right-Sided Major Hepatectomy for Treatment of
      a Tumor Causing Severe Inferior Vena Cava Compression: A Novel Strategy Using the
      Modified Liver-Hanging Maneuver.
AB  - BACKGROUND: Massive bleeding during major hepatectomy is associated with greater
      mortality and morbidity.1 Our previous study shows that inferior vena cava (IVC)
      compression by tumor and an anterior approach without the liver-hanging maneuver
      (LHM) are risk factors for massive bleeding.2 The LHM is useful for controlling
      bleeding in deeper parenchymal transection planes.3 However, severe compression
      of the IVC by tumor makes it difficult to insert a hanging tape.4 The study shows
      a novel modified LHM strategy for severe IVC compression to minimize
      intraoperative bleeding. METHODS: The procedure was disassembled into six steps:
      (1) the glissonian bifurcation is encircled using an extrahepatic approach (2)
      the hepatic ligaments are dissected, and the root of each hepatic vein trunk is
      exposed (3) the left lobe is fully mobilized, and the short hepatic veins are
      carefully dissected with a systematic procedure established from hemi-left lobe
      procurement in living donor liver transplantation5 (4) the tape is inserted from
      the space between the right and middle hepatic vein trunks into the glissonian
      bifurcation along the anterior surface of the IVC (5) liver parenchymal
      transection is performed with upward pulling of the tape (6) the right hepatic
      vein is dissected, and the right lobe is dissected from the diaphragm and the
      right hepatic ligaments. RESULTS: Right hepatectomy with this procedure was
      performed for two patients with IVC compressed by hepatocellular carcinoma. The
      operative times were respectively 483 and 396 min. The respective estimated blood
      losses were 1195 and 485 ml, without transfusion. Both patients had acceptable
      outcomes without complications. CONCLUSION: The novel modified LHM strategy
      ensured minimal bleeding in the resection of a huge liver tumor causing severe
      IVC compression.

PMID- 29450752
TI  - Racial and Socioeconomic Differences in the Use of High-Volume Commission on
      Cancer-Accredited Hospitals for Cancer Surgery in the United States.
AB  - BACKGROUND: Although major cancer surgery at a high-volume hospital is associated
      with lower postoperative mortality, the use of such hospitals may not be equally
      distributed. OBJECTIVE: Our aim was to study socioeconomic and racial differences
      in cancer surgery at Commission on Cancer (CoC)-accredited high-volume hospitals.
      METHODS: The National Cancer Database (NCDB) was used to identify patients
      undergoing surgery for colon, esophageal, liver, and pancreatic cancer from 2003
      to 2012. Annual hospital volume for each cancer was categorized using quartiles
      of patient volume. Patient-level predictors of surgery at a high-volume hospital,
      trends in the use of a high-volume hospital, and adjusted likelihood of surgery
      at a high-volume hospital in 2012 versus 2003 were analyzed. RESULTS: African
      American patients were less likely to undergo surgery at a high-volume hospital
      for esophageal (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49-0.73) and
      pancreatic cancer (OR 0.83, 95% CI 0.74-0.92), while uninsured patients and those
      residing in low educational attainment zip codes were less likely to undergo
      surgery at a high-volume hospital for esophageal, liver, and pancreatic cancer.
      In 2012, African Americans, uninsured patients, and those from low educational
      attainment zip codes were no more likely to undergo surgery at a high-volume
      hospital than in 2003 for any cancer type. These differences were not seen in
      colon cancer patients, for whom significant regionalization was not seen.
      CONCLUSIONS: Differences in the use of CoC-accredited high-volume hospitals for
      major cancer surgery were seen nationwide and persisted over the duration of the
      study. Strategies to increase referrals and/or access to high-volume hospitals
      for African American and socioeconomically disadvantaged patients should be
      explored.

PMID- 29450753
TI  - Use of Breast Imaging After Treatment for Locoregional Breast Cancer (AFT-01).
AB  - BACKGROUND: Annual mammography is recommended after breast cancer treatment.
      However, studies suggest its under-utilization for Medicare patients. Utilization
      in the broader population is unknown, as is the role of breast magnetic resonance
      imaging (MRI). Understanding factors associated with imaging use is critical to
      improvement of adherence to recommendations. METHODS: A random sample of 9835
      eligible patients receiving surgery for stages 2 and 3 breast cancer from 2006 to
      2007 was selected from the National Cancer Database for primary data collection.
      Imaging and recurrence data were abstracted from patients 90 days after surgery
      to 5 years after diagnosis. Factors associated with lack of imaging were assessed
      using multivariable repeated measures logistic regression with generalized
      estimating equations. Patients were censored for death, bilateral mastectomy, new
      cancer, and recurrence. RESULTS: Of 9835 patients, 9622, 8702, 8021, and 7457
      patients were eligible for imaging at surveillance years 1 through 4
      respectively. Annual receipt of breast imaging declined from year 1 (69.5%) to
      year 4 (61.0%), and breast MRI rates decreased from 12.5 to 5.8%. Lack of imaging
      was associated with age 80 years or older and age younger than 50 years, black
      race, public or no insurance versus private insurance, greater comorbidity,
      larger node-positive hormone receptor-negative tumor, excision alone or
      mastectomy, and no chemotherapy (p < 0.005). Receipt of breast MRI was associated
      with age younger than 50 years, white race, higher education, private insurance,
      mastectomy, chemotherapy, care at a teaching/research facility, and MRI 12 months
      before diagnosis (p < 0.05). CONCLUSION: Under-utilization of mammography after
      breast cancer treatment is associated with sociodemographic and clinical factors,
      not institutional characteristics. Effective interventions are needed to increase
      surveillance mammography for at-risk populations. ClinicalTrials.gov Identifier:
      NCT02171078.

PMID- 29450754
TI  - Neural Invasion is a Significant Contributor to Peritoneal Recurrence in Signet
      Ring Cell Gastric Carcinoma.
AB  - BACKGROUND: Gastric signet ring cell carcinoma (SRC) has shown a favorable
      outcome in early stages but has a worse prognosis than non-SRC in advanced
      stages. However, the cause for this stage-dependent prognostic impact has not
      been determined. This study aimed to compare clinicopathologic features and
      recurrence patterns between gastric SRC and non-SRC in a cohort of Eastern
      patients. METHODS: This study reviewed the prospectively collected data of 764
      patients undergoing curative resection for gastric cancer from 2005 to 2008. The
      demographics, clinicopathologic characteristics, disease-specific survival (DSS)
      rate, and recurrence-free survival (RFS) rate of the patients were analyzed.
      RESULTS: The SRC patients (n = 176) had a worse prognosis than the non-SRC
      patients (n = 588), especially in stages T3 and T4. Peritoneal recurrence and the
      incidence of neural invasion (NI) were significantly increased in the SRC
      patients, albeit only in stages T3 and T4. In the T3 and T4 patients with NI,
      peritoneal recurrence occurred more frequently in SRC than in non-SRC (28.7% vs.
      13.7%; p = 0.001), but not in the T3 and T4 patients without NI. Only in the
      patients with NI, SRC led to a significantly shorter DSS (67.6 vs. 90.7 months; p
      = 0.008) and RFS (67.1 vs. 80.3 months; p = 0.036) than non-SRC. CONCLUSIONS:
      This report is the first to present the relationship between NI and peritoneal
      recurrence as the cause of stage-dependent prognoses for SRC. A better
      understanding of NI may lend insight into cancer spread and recurrence,
      especially in gastric SRC.

PMID- 29450755
TI  - Efficacy of Adjuvant S-1 Versus XELOX Chemotherapy for Patients with Gastric
      Cancer After D2 Lymph Node Dissection: A Retrospective, Multi-Center
      Observational Study.
AB  - BACKGROUND: After curative resection of gastric cancer with D2 lymph node
      dissection, postoperative adjuvant chemotherapy with S-1 or capecitabine plus
      oxaliplatin (XELOX) is considered to be standard therapy in Eastern countries.
      This study aimed to compare the efficacies of adjuvant S-1 and XELOX chemotherapy
      for gastric cancer patients after D2 dissection based on disease-free survival
      (DFS). METHODS: This retrospective observational study was conducted at 29
      tertiary hospitals in Korea. Of 1898 patients who underwent curative resection
      and received adjuvant chemotherapy for gastric cancer between February 2012 and
      December 2013, 1088 patients who met the eligibility criteria were enrolled in
      the study. After propensity score-matching, the 3-year disease-free survival rate
      (DFS) was used to compare efficacies directly between adjuvant XELOX and S-1
      chemotherapies for patients with stage 2 or 3 gastric cancer after D2
      gastrectomy. RESULTS: The 3-year DFS rates for the S-1 and XELOX groups did not
      differ significantly among disease stages 2A, 2B, and 3A (all p > 0.05). However,
      the survival rates for the S-1 group were significantly lower than for the XELOX
      group for stage 3B (65.8% vs. 68.6%; p = 0.019) and stage 3C (48.4% vs. 66.7%; p
      = 0.002) gastric cancer. The hazard ratios (HRs) of S-1 chemotherapy for
      recurrence compared with XELOX for stages 3B and 3C were respectively 2.030 [95%
      confidence interval (CI), 1.110-3.715; p = 0.022] and 2.732 (95% CI 1.427-5.234;
      p = 0.002). CONCLUSIONS: Adjuvant XELOX chemotherapy was more effective than S-1
      for patients with stage 3B or 3C gastric cancer after D2 lymph node dissection.

PMID- 29450756
TI  - Risk Stratification According to the Prognostic Nutritional Index for Predicting
      Postoperative Complications After Lung Cancer Surgery.
AB  - BACKGROUND: The prognostic nutritional index (PNI), an immune nutritional marker
      based on serum albumin levels and total lymphocyte count, predicts postoperative
      complications in various types of malignancies. However, the clinical
      significance of the PNI for postoperative complications following lung cancer
      surgery is uncertain. METHODS: Patients with resected non-small cell lung cancer
      (n = 515) were retrospectively analyzed and the relationship between the
      preoperative PNI and postoperative complications was evaluated. RESULTS:
      Multivariate logistic regression analysis revealed that a preoperative low PNI
      was a significant independent predictor of postoperative complications of Clavien
      Dindo Grade >= II (odds ratio: 1.06 per unit decrease, 95.0% confidence interval
      1.01-1.11). Patients were divided into three groups according to the preoperative
      PNI: normal (>= 50; n = 324), mildly low (< 50, >= 45; n = 134), and severely low
      (< 45; n = 57). The incidence of postoperative complications of Grade >= II and
      Grade >= III in the normal, mildly low, and severely low PNI groups was 22.2,
      39.6, and 42.1% and 7.1, 16.4, and 22.8%, respectively. The incidence of
      postoperative complications of Grade >= II and Grade >= III was significantly
      higher in the mildly low and severely low PNI groups than in the normal PNI group
      (p < 0.001 and p < 0.001, respectively). The incidence of air leak, pneumonia,
      and extrapulmonary infection, but not arrhythmia, was significantly higher in the
      mildly low and severely low PNI groups than in the normal PNI group. CONCLUSIONS:
      The PNI could be a useful marker to predict the risk of postoperative
      complications after lung cancer surgery.

PMID- 29450757
TI  - Enhanced expression of ginsenoside biosynthetic genes and in vitro ginsenoside
      production in elicited Panax sikkimensis (Ban) cell suspensions.
AB  - Dual metabolite, i.e., ginsenoside and anthocyanin, co-accumulating cell
      suspensions of Panax sikkimensis were subjected to elicitation with culture
      filtrates of Serratia marcescens (SD 21), Bacillus subtilis (FL11), Trichoderma
      atroviridae (TA), and T. harzianum (TH) at 1.25% and 2.5% v/v for 1- and 3-week
      duration. The fungal-derived elicitors (TA and TH) did not significantly affect
      biomass accumulation; however, bacterial elicitors (SD 21 and FL11), especially
      SD 21, led to comparable loss in biomass growth. In terms of ginsenoside content,
      differential responses were observed. A maximum of 3.2-fold increase (222.2 mg/L)
      in total ginsenoside content was observed with the use of 2.5% v/v TH culture
      filtrate for 1 week. Similar ginsenoside accumulation was observed with the use
      of 1-week treatment with 2.5% v/v SD 21 culture filtrate (189.3 mg/L) with a 10
      fold increase in intracellular Rg2 biosynthesis (31 mg/L). Real-time PCR analysis
      of key ginsenoside biosynthesis genes, i.e., FPS, SQS, DDS, PPDS, and PPTS,
      revealed prominent upregulation of particularly PPTS expression (20-23-fold),
      accounting for the observed enhancement in protopanaxatriol ginsenosides.
      However, none of the elicitors led to successful enhancement in in vitro
      anthocyanin accumulation as compared to control values.

PMID- 29450758
TI  - Overexpression of AlTMP2 gene from the halophyte grass Aeluropus littoralis in
      transgenic tobacco enhances tolerance to different abiotic stresses by improving
      membrane stability and deregulating some stress-related genes.
AB  - Herein, we report isolation of the AlTMP2 gene from the halophytic C4 grass
      Aeluropus littoralis. The subcellular localization suggested that AlTMP2 is a
      plasma membrane protein. In A. littoralis exposed to salt and osmotic stresses,
      the AlTMP2 gene was induced early and at a high rate, but was upregulated
      relatively later in response to abscisic acid and cold treatments. Expression of
      AlTMP2 in tobacco conferred improved tolerance against salinity, osmotic, H2O2,
      heat, and freezing stresses at the germination and seedling stages. Under control
      conditions, no growth or yield penalty were mentioned in transgenic plants due to
      the constitutive expression of AlTMP2. Interestingly, under greenhouse
      conditions, the seed yield of transgenic plants was significantly higher than
      that of non-transgenic (NT) plants grown under salt or drought stress.
      Furthermore, AlTMP2 plants had less electrolyte leakage, higher membrane
      stability, and lower Na+ and higher K+ accumulation than NT plants. Finally, six
      stress-related genes were shown to be deregulated in AlTMP2 plants relative to NT
      plants under both control and stress conditions. Collectively, these results
      indicate that AlTMP2 confers abiotic stress tolerance by improving ion
      homeostasis and membrane integrity, and by deregulating certain stress-related
      genes.

PMID- 29450759
TI  - Gene expression and population polymorphism of maize Iranian mosaic virus in Zea
      mays, and intracellular localization and interactions of viral N, P, and M
      proteins in Nicotiana benthamiana.
AB  - Maize Iranian mosaic virus (MIMV; Mononegavirales, Rhabdoviridae,
      Nucleorhabdovirus) infects maize and several other poaceous plants. MIMV encodes
      six proteins, i.e., nucleocapsid protein (N), polymerase cofactor phosphoprotein
      (P), putative movement protein (P3), matrix protein (M), glycoprotein (G), and
      large RNA-dependent RNA polymerase (L). In the present study, MIMV gene
      expression and genetic polymorphism of an MIMV population in maize were
      determined. N, P, P3, and M protein genes were more highly expressed than the 5'
      terminal G and L genes. Twelve single nucleotide polymorphisms were identified
      across the genome within a MIMV population in maize from RNA-Seq read data pooled
      from three infected plants indicating genomic variations of potential importance
      to evolution of the virus. MIMV N, P, and M proteins that are known to be
      involved in rhabdovirus replication and transcription were characterized as to
      their intracellular localization and interactions. N protein accumulated
      exclusively in the nucleus and interacted with itself and with P protein. P
      protein accumulated in both the nucleus and cell periphery and interacted with
      itself, N and M proteins in the nucleus. M protein was localized in the cell
      periphery and on endomembranes, and interacted with P protein in the nucleus.
      MIMV proteins show a distinctive combination of intracellular localizations and
      interactions.

PMID- 29450760
TI  - Association of facet tropism and orientation with lumbar disc herniation in young
      patients.
AB  - Facet tropism and orientation are thought to be associated with lumbar disc
      herniation (LDH), but the relationship is not well established. Moreover, the
      effect of facet joint on LDH has not been outlined in young patients. The
      objective of this study was to investigate the associations of facet joint
      tropism and orientation with LDH in young patients (18-35 years) by computed
      tomography (CT). Fifty-three patients with LDH and 129 with neither LDH nor low
      back pain (18-35 years) were included in this study. The facet joint angles were
      measured for each facet joint by CT as per the method described by Noren et al.
      We defined facet tropism as a bilateral angle difference > 5 degrees . Young
      cases with neither LDH nor low back pain were used as the control group. The
      results showed that LDH was significantly associated with more coronal facet
      joint orientation at L1-2 (p = 0.009), L2-3 (p = 0.004), and L3-4 (p = 0.004). No
      association was established between facet tropism and LDH. This study revealed
      that facet joint orientation was associated with LDH in young patients (18-35
      years); they were more of coronal facing at upper levels. Also, the facet tropism
      was not associated with LDH.

PMID- 29450761
TI  - An electroglottographical analysis-based discriminant function model
      differentiating multiple sclerosis patients from healthy controls.
AB  - Dysarthrophonia is a predominant symptom in many neurological diseases, affecting
      the quality of life of the patients. In this study, we produced a discriminant
      function equation that can differentiate MS patients from healthy controls, using
      electroglottographic variables not analyzed in a previous study. We applied
      stepwise linear discriminant function analysis in order to produce a function and
      score derived from electroglottographic variables extracted from a previous
      study. The derived discriminant function's statistical significance was
      determined via Wilk's lambda test (and the associated p value). Finally, a 2 * 2
      confusion matrix was used to determine the function's predictive accuracy,
      whereas the cross-validated predictive accuracy is estimated via the "leave-one
      out" classification process. Discriminant function analysis (DFA) was used to
      create a linear function of continuous predictors. DFA produced the following
      model (Wilk's lambda = 0.043, chi2 = 388.588, p < 0.0001, Tables 3 and 4): D (MS
      vs controls) = 0.728*DQx1 mean monologue + 0.325*CQx monologue + 0.298*DFx1 90%
      range monologue + 0.443*DQx1 90% range reading - 1.490*DQx1 90% range monologue.
      The derived discriminant score (S1) was used subsequently in order to form the
      coordinates of a ROC curve. Thus, a cutoff score of - 0.788 for S1 corresponded
      to a perfect classification (100% sensitivity and 100% specificity, p = 1.67e
      22). Consistent with previous findings, electroglottographic evaluation
      represents an easy to implement and potentially important assessment in MS
      patients, achieving adequate classification accuracy. Further evaluation is
      needed to determine its use as a biomarker.

PMID- 29450762
TI  - Effect of prior application with and without post-injury treatment with low-level
      laser on the modulation of key proteins in the muscle repair process.
AB  - The aim of the present study was to evaluate the effects of LLLT prior to muscle
      injury with and without post-injury irradiation on the expression of isoforms of
      myosin heavy chain (MyHC), calcineurin (CaN), and myostatin during the repair
      process. Wistar rats were divided into five groups: control (n = 7); injury (n =
      21); LLLT + injury (n = 21); injury + LLLT (n = 21), and LLLT + injury + LLLT (n
      = 21). Cryoinjury was performed on the tibialis anterior (TA) muscle. The injured
      groups were euthanized at 3, 7, and 14 days after injury. LLLT was performed
      using an infrared laser (780 nm) with the following parameters: 10 J/cm2, 40 mW,
      10 s per point, 8 points, and 3.2 J of total energy. At the end of each period,
      the TA muscle was removed for the analysis of MyHC, CaN, and myostatin gene
      expression using real-time PCR. The data were tested statistically by Kruskal
      Wallis with Dunn's post hoc test (p < 0.05). The results demonstrated that prior
      irradiation reduced the mRNA expression of all proteins at 3 days. Post
      irradiation reduced the mRNA expression of MyHC-1, MyHC-2a, MyHC-2b, and CaN at 7
      days. Prior irradiation combined with post-injury irradiation reduced the mRNA
      expression of MyHC-2x and CaN at 14 days and increased the mRNA expression of
      myostatin in the same period. In conclusion, different protocols of
      photobiomodulation can modulate the expression of the different isoforms of MyHC,
      CaN, and myostatin during the repair process. It is noteworthy that the
      combination of the prior and post-injury irradiation was the protocol that most
      promoted changes in the final phase of the repair process.

PMID- 29450763
TI  - Effects of 915 nm laser irradiation on human osteoblasts: a preliminary in vitro
      study.
AB  - Photobiomodulation (PBM) is a non-invasive treatment that uses laser or led
      devices making its effects a response to light and not to heat. The possibility
      of accelerating dental implant osteointegration and orthodontic movements and the
      need to treat refractory bone lesions, such as bisphosphonate related
      osteonecrosis of the jaws, has led researchers to consider the effects of PBM on
      bone for dentistry purposes. The aim of our study was to investigate the effects
      of 915 nm light supplied with a GaAs diode laser on human osteoblasts in vitro.
      Osteoblasts were isolated from mandibular cortical bone of a young healthy donor.
      The irradiation parameters were as follows: doses = 5, 15 and 45 J/cm2; power
      densities = 0.12 and 1.25 W/cm2; and irradiation times = 41.7, 125 and 375 s. We
      performed one irradiation per day for 3 and 6 days to study proliferation and
      differentiation, respectively. Microscopic analysis showed a greater amount of
      bone nodules in samples treated with 5 J/cm2 and 0.12 W/cm2 compared to controls
      (56.00 +/- 10.44 vs 19.67 +/- 7.64, P = 0.0075). Cell growth and quantification
      of calcium deposition did not show any differences when comparing irradiated and
      non-irradiated samples. Photobiomodulation, with the parameters investigated in
      the present study, positively modulated the mineralization process in human
      osteoblasts, inducing the formation of a greater amount of bone nodules, but did
      not increase cell proliferation.

PMID- 29450764
TI  - Impact of Well-being Interventions for Siblings of Children and Young People with
      a Chronic Physical or Mental Health Condition: A Systematic Review and Meta
      Analysis.
AB  - Siblings of children and young people with a chronic illness are at increased
      risk of poor psychological functioning. A number of studies have attempted to
      implement and evaluate interventions targeting the psychological well-being of
      this at-risk group. This systematic review summarises the evidence regarding
      psychological functioning of siblings following an intervention targeting their
      well-being. The meta-analysis considered behaviour and knowledge, two of the most
      frequently studied outcomes. The following databases were used: PsycINFO, EMBASE,
      CINAHL, PubMed, Scopus and Web of Science. Seventeen studies were eligible to be
      included in the systematic review and eight in the meta-analysis. Results from
      the systematic review reflected the inconsistency of intervention evaluations in
      this area with a high level of heterogeneity and a total of 23 outcomes
      considered across the 17 included studies. The meta-analysis estimated effect
      sizes using a standardised mean difference (SMD) approach. Pre-post analysis
      suggested significant improvement in behavioural outcomes and knowledge of their
      sibling's health conditions with a SMD of - 0.44 [95% CI (- 0.6, - 0.29); p =
      0.000] and 0.69 [(95% CI = 0.42, 0.96); p = 0.000], respectively. The SMD was not
      significant for behavioural outcomes when considering treatment-control studies.
      In conclusion, the findings suggest interventions for well-being have a positive
      effect on the psychological functioning of siblings of children and young people
      with a chronic illness, but their specificity needs to be established. There is a
      need for further, more methodologically robust research in this area.

PMID- 29450765
TI  - Impact of platelet reactivity on 5-year clinical outcomes following percutaneous
      coronary intervention: a landmark analysis.
AB  - We investigated the impact of suboptimal platelet reactivity on clinical outcomes
      after percutaneous coronary intervention (PCI). We enrolled 500 patients with
      stable coronary artery disease undergoing elective PCI. Platelet reactivity was
      measured before PCI using the VerifyNow P2Y12 assay. Primary endpoint was the
      incidence of ischemic or bleeding events at 1 month and 5 years. Patients with
      high platelet reactivity (HPR) showed significantly higher rates of ischemic
      events both during the 1st month after PCI (HR 2.06, 95% CI 1.02-4.06), and
      beyond 1 month compared with patients without HPR (HR 1.73, 95% CI 1.02-2.95).
      Conversely, compared with patients without low platelet reactivity (LPR),
      patients with LPR presented significantly higher rates of bleeding only during
      the 1st month (HR 3.67, 95% CI 1.68-8.02). In conclusion, pre-procedural HPR is
      associated with ischemic events even beyond the 1st month after PCI. The
      association of LPR with bleeding events seems to be confined to the
      periprocedural period.

PMID- 29450766
TI  - Septal myectomy for hypertrophic cardiomyopathy: important surgical knowledge and
      technical tips in the era of increasing alcohol septal ablation.
AB  - Hypertrophic cardiomyopathy (HCM) is the most commonly inherited cardiac disease
      recent studies suggest a prevalence as high as 1 in 200. For symptomatic patients
      with obstructive HCM who are refractory to medical therapy, septal reduction is
      indicated. Septal myectomy (SM) is considered the gold standard septal reduction
      technique. However, due to a shortage of surgeons who are experienced in this
      technique, alcohol septal ablation (ASA) has overtaken SM as the most commonly
      performed procedure for obstructive HCM. In this review, we summarize the
      existing literature comparing SM with ASA and describe recent innovations in
      operative technique, including a detailed description of the approach used at our
      institution.

PMID- 29450767
TI  - Epididymo-orchitis caused by enteric organisms in men > 35 years old: beyond
      fluoroquinolones.
AB  - Epididymo-orchitis is a common urological condition in men of all ages, causing a
      unilateral or bilateral swelling of the epididymis and/or testis. It is
      frequently caused by sexually transmitted infections, Chlamydia trachomatis and
      Neisseria gonorrheae, as well as common enteric organisms implicated in urinary
      tract infections. Men over 35 years old may develop epididymo-orchitis associated
      with enteric organisms, often associated with functional bladder outlet problems
      such as benign prostatic hyperplasia or urethral stricture disease.
      Fluoroquinolones, especially ciprofloxacin, have long been the mainstay of
      treatment for these infections; however, rising resistance to ciprofloxacin in E.
      coli isolates in Europe and the USA means that there is an unprecedented
      necessity for alternative antimicrobials with adequate penetration into genital
      tissues (epididymis and testes) to allow appropriate and comprehensive treatment
      of epididymo-orchitis in this group of patients.

PMID- 29450769
TI  - Correction to: Air quality and acute myocardial infarction in adults during the
      2016 Hangzhou G20 summit.
AB  - Unfortunately, the original publication of this paper contains a mistake. The
      correct name of the 1st Author is Ming-Wei Wang.

PMID- 29450768
TI  - CC398 Staphylococcus aureus subpopulations in Belgian patients.
AB  - Studies based on genome-wide single nucleotide polymorphisms (SNPs) supported the
      existence of two subpopulations in clonal complex (CC) 398 Staphylococcus aureus:
      an ancestral human-adapted clade (HC) and an animal-associated clade (AC). In
      this study, we have investigated the occurrence of genetic markers that allow
      discrimination of these subpopulations among CC398 isolates collected during 2014
      to 2016 from human patients in Belgium. A collection of isolates was investigated
      by means of spa-typing and 16S-mecA-nuc PCR. CC398 isolates were classified as
      belonging to the human or the animal clade by using a canonical SNPs PCR and
      further studied by antimicrobial susceptibility and the presence of toxins,
      immune evasion cluster (IEC), and resistance genes. A total of 124 (7.8%) human
      isolates belonged to CC398. They were grouped into HC (n = 58) or AC (n = 66).
      The genes erm(T), pvl, chp, and scn were predominantly found in HC-CC398, while
      AC-CC398 isolates carried more frequently than the mecA, erm(C), tet(K), tet(M),
      and tet(L) genes. Different combinations of gene profiles were observed according
      to the clade. CC398 isolates from Belgian patients belonged to different
      subpopulations including typical HC and AC-isolates. Few HC-strains with mecA and
      AC-isolates harboring IEC were found. CC398 isolates from Belgian patients
      belonged to different subpopulations including typical HC and AC-isolates, as
      well as new emerging subpopulations that underline the ability of this lineage to
      acquire resistance and virulence genes. Further research is needed to evaluate
      the emergence of these subpopulations in the clinical setting.

PMID- 29450770
TI  - How can water quality be improved when the urban waste water directive has been
      fulfilled? A case study of the Lot river (France).
AB  - The Lot river, a major tributary of the downstream Garonne river, the largest
      river on the Northern side of the Pyrenees Mountains, was intensively studied in
      the 1970s. A pioneering program called "Lot Riviere Claire" provided a diagnosis
      of water quality at the scale of the whole watershed and proposed an ambitious
      program to manage nutrient pollution and eutrophication largely caused by urban
      wastewater releases. Later on, the implementation of European directives from
      1991 to 2000 resulted in the nearly complete treatment of point sources of
      pollution in spite of a doubling of the basin's population. At the outlet of the
      Lot river, ammonium and phosphate contamination which respectively peaked to 1 mg
      N-NH4 L-1 and 0.3 mg P-PO4 L-1 in the 1980s returned to much lower levels in
      recent years (0.06 mg N-NH4 L-1 and 0.02 mg P-PO4 L-1), a reduction by a factor
      15. However, during this time, nitrate contamination has regularly increased
      since the 1980s, from 0.5 to 1.2 mg N-NO3 L-1 in average, owing to the
      intensification of agriculture and livestock farming. Application of the
      Riverstrahler model allowed us to simulate the water quality of the Lot drainage
      network for the 2002-2014 period. We showed that, with respect to algal
      requirements, phosphorus and silica are well balanced, but nitrogen remains
      largely in excess over phosphorus and silica. This imbalance can be problematic
      for the ecological status of the water bodies. Using the model, for simulating
      various scenarios of watershed management, we showed that improvement of urban
      wastewater treatment would not result in any significant change in the river's
      water quality. Even though arable land occupies a rather limited fraction of the
      watershed area, only the adoption of better farming practices or more radical
      changes in the agro-food system could reverse the trend of increasing nitrate
      contamination.

PMID- 29450771
TI  - Fetal exposure markers of dioxins and dioxin-like PCBs.
AB  - Fetal exposure to polychlorinated biphenyls (PCBs), polychlorinated-p
      dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) have been
      associated with a number of adverse health outcomes. Although the placenta acts
      as a barrier between the mother and the fetus, these contaminants transfer
      through the placenta exposing the fetus. Several studies have investigated
      placental transfer, but few have assessed the co-variation among these
      contaminants. Maternal blood, cord blood, and cord tissue were collected from 41
      Japanese mother-infant pairs and analyzed for dioxin-like PCBs and PCDD/Fs.
      Hierarchical cluster analysis followed by principal component analysis were used
      to assess the co-variation. Two stable clusters of dioxin-like PCBs were found in
      maternal and cord blood. One cluster of low/medium chlorinated dioxin-like PCBs
      was present in all three matrices with 2,3',4,4',5-PeCB(#118) and 3,3',4,4',5
      PeCB(#126) explaining the majority of the clusters' variances. Medium/high
      chlorinated dioxin-like PCBs clustered in maternal blood and cord blood but not
      in cord tissue. 2,3,4,4',5-PeCB(#114) and 2,3,3',4,4',5,5'-HpCB(#189) explained
      the majority of the clusters' variances. There was a substantial correlation
      between the sum of dioxin-like PCBs and total PCDD/F in all three matrices. The
      sum of the four suggested PCBs plus 3,3',4,4'-TeCB(#77) correlated well with
      total PCDD/F in all three matrices. Apart from the dioxin-like PCBs, little co
      variation existed among the studied contaminants. The five PCBs can be used as
      fetal exposure markers for dioxin and dioxin-like PCBs in maternal and cord blood
      respectively. In cord tissue, more higher chlorinated dioxin-like PCBs need to be
      measured as well.

PMID- 29450772
TI  - Dissolved organic matter distribution and its association with colloidal aluminum
      and iron in the Selenga River Basin from Ulaanbaatar to Lake Baikal.
AB  - The Selenga River Basin (Mongolia and Russia) has suffered from heavy metal
      contamination by placer gold mining and urban activities in recent decades. The
      objectives of this study were to provide the first distribution data of dissolved
      organic matter (DOM) and humic substances (HS) in this data-scarce region, and to
      investigate their association with dissolved and colloidal metals. Two sampling
      campaigns were conducted in August of 2013 and 2014. A constant proportion of HS
      (%HS; coefficient of variation of 2%) was observed from the headwater of Tuul
      River to the end of the delta before Lake Baikal, spanning > 1000 km in distance.
      The relationships were determined as [HS] = 0.643 * [DOM] (R2 = 0.996, P <
      0.001), and this value (%HS = 64.3) is recommended as an input parameter for
      metal speciation modeling based on samples collected from the rivers. The DOM and
      metal (Al and Fe) concentrations in samples doubled through the Zaamar Goldfield
      mining area, but the influence was mitigated by mixing with the larger Orkhon
      River, which has better water quality. Metals were mainly present as colloids and
      had a strong positive correlation with DOM (Al r = 0.81, P < 0.01; Fe r = 0.61, P
      < 0.01), suggesting that DOM sustains colloidal Al and Fe in solution and they
      are co-transported in the Selenga River Basin. Land use changes affect water
      quality and metal speciation and therefore have major implications for the fate
      of metals.

PMID- 29450773
TI  - Influence of Mn2+ ions on the corrosion mechanism of lead-based anodes and the
      generation of heavy metal anode slime in zinc sulfate electrolyte.
AB  - The influence of Mn2+ ions on the generation of heavy metal anode slime during
      zinc electrolysis industry was extensively investigated using several
      electrochemical methods, electron microscope technologies, and particle size
      analysis. Results showed that the Mn2+ could obviously promote oxygen evolution
      reaction (OER) and thereby weaken oxidation efficiency of Mn2+ (etaMnO2) and
      dissolution of Pb2+. The significant improvement in kinetic parameters for OER
      was found in electrolytes of 1 and 3 g/L Mn2+, but became unstable as the Mn2+
      concentration increased to 10 g/L. This result was correlated with much different
      properties of oxide layers that its changes of microstructure are involved in,
      since it confirmed that the positive role of compact oxide layers in contributing
      to high corrosion resistance and activity for OER, but excessive Mn2+, resulted
      in its micromorphology of overthickness and instability. Such differences
      resulted from the effect of the Mn2+ concentration fluctuation on kinetic rates
      of the nucleation growth process. The formation and adsorption of intermediate
      MnO2-OHads identified as the controlled step for Mn2+ catalyzing OER was also
      recommended. The generation mechanism of anode slime was found to be changed in
      essence due to varying Mn2+ concentrations. In electrolyte of 1 g/L Mn2+, results
      revealed that the root cause of excessive small suspended anode slime (around 20
      MUm) was the change of the initial pathway of Mn2+ electro-oxidation, whereas, it
      showed great improvement in the settling performance as the Mn2+ concentration
      was increased to 10 g/L. Considering the potential of optimizing Mn2+
      concentrations as a cleaner approach to control anode slime, deepening the
      understanding of the impact mechanism of Mn2+ can provide new insights into
      intervention in the generation of anode slime.

PMID- 29450774
TI  - Removal of tetracyclines, sulfonamides, and quinolones by industrial-scale
      composting and anaerobic digestion processes.
AB  - This study evaluated and compared the removal of antibiotics by industrial-scale
      composting and anaerobic digestion at different seasons. Twenty compounds
      belonged to three classes of widely used veterinary antibiotics (i.e.,
      tetracyclines, sulfonamides, and quinolones) were investigated. Results show that
      of the three groups of antibiotics, tetracyclines were dominant in swine feces
      and poorly removed by anaerobic digestion with significant accumulation in
      biosolids, particularly in winter. Compared to that in winter, a much more
      effective removal (> 97%) by anaerobic digestion was observed for sulfonamides in
      summer. By contrast, quinolones were the least abundant antibiotics in swine
      feces and exhibited a higher removal by anaerobic digestion in winter than in
      summer. The overall removal of antibiotics by aerobic composting could be more
      than 90% in either winter or summer. Nevertheless, compost products from
      livestock farms in Beijing contained much higher antibiotics than commercial
      organic fertilizers. Thus, industrial composting standards should be strictly
      applied to livestock farms to further remove antibiotics and produce high quality
      organic fertilizer.

PMID- 29450775
TI  - Simultaneous immobilization of cadmium and lead in contaminated soils by hybrid
      bio-nanocomposites of fungal hyphae and nano-hydroxyapatites.
AB  - Self-aggregation of bulk nano-hydroxyapatites (n-HAPs) undermines their
      immobilization efficiencies of heavy metals in the contaminated soils. Here, the
      low-cost, easily obtained, and environment-friendly filamentous fungi have been
      introduced for the bio-matrices of the hybrid bio-nanocomposites to potentially
      solve such problem of n-HAPs. According to SEM, TEM, XRD, and FT-IR analyses, n
      HAPs were successfully coated onto the fungal hyphae and their self-aggregation
      was improved. The immobilization efficiencies of diethylene-triamine-pentaacetic
      acid (DTPA)-extractable Cd and Pb in the contaminated soils by the bio
      nanocomposites were individually one to four times of that by n-HAPs or the
      fungal hyphae. Moreover, the Aspergillus niger-based bio-nanocomposite (ANHP) was
      superior to the Penicillium Chrysogenum F1-based bio-nanocomposite (PCHP) in
      immobilization of Cd and Pb in the contaminated soils. In addition, the results
      of XRD showed that one of the potential mechanisms of metal immobilization by the
      hybrid bio-nanocomposites was dissolution of n-HAPs followed by precipitation of
      new metal phosphate minerals. Our results suggest that the hybrid bio
      nanocomposite (ANHP) can be recognized as a promising soil amendment candidate
      for effective remediation on the soils simultaneously contaminated by Cd and Pb.

PMID- 29450776
TI  - Modulatory role of GSTT1 and GSTM1 in Punjabi agricultural workers exposed to
      pesticides.
AB  - Glutathione S-transferases are important detoxification enzymes involved in the
      metabolism of endogenous as well as exogenous compounds. Individuals differ in
      metabolic capacity due to inherited genetic variations. Due to the polymorphism
      exhibited by GSTT1 and GSTM1 that results in the complete loss of function, the
      present study was aimed towards the determination of the frequency distribution
      of GSTT1 and GSTM1 in agricultural workers in Punjab, India. The study aimed to
      investigate their contribution in susceptibility to increased disease risk. A
      total of 513 subjects were included in this study, out of which 250 were
      agriculture workers and 263 were non-exposed occupationally. GSTT1 and GSTM1 null
      genotype distribution was analyzed through multiplex-PCR method. Complete gene
      deletion in either of the genes was strongly associated with an increased risk
      (OR = 1.8; 95% CI = 1.3-2.6; p < 0.0008) of DNA/cytogenetic damage, cancer,
      infertility, and many other serious health effects. Therefore, homozygous
      deletion in GSTT1 or GSTM1 could play a modulatory role in health of workers with
      long-term exposure to pesticides.

PMID- 29450777
TI  - Recovery and characterization of proteins from pangas (Pangasius pangasius)
      processing waste obtained through pH shift processing.
AB  - Study was conducted to recover proteins from pangas (Pangasius pangasius)
      processing waste (fillet frames) using pH shift method and to characterize the
      recovered isolates. pH 2.0 from acidic range and pH 13.0 from alkaline range were
      found to have maximum protein recovery (p < 0.05). During the recovery process,
      acidic pH (pH 2.0) was found to have minimal effect on proteins resulting in more
      stable isolates and strong protein gels. Alkaline pH (pH 13.0) caused protein
      denaturation resulting in less stable proteins and poor gel network. Both acidic
      and alkaline-aided processing caused significant (p < 0.05) reductions in total
      lipid, myoglobin, and pigment content thus by resulting in whiter protein
      isolates and gels. The content of total essential amino acids increased during pH
      shift processing, indicating the enrichment of essential amino acids. No
      microbial counts were detected in any of the isolates prepared using acid and
      alkaline extraction methods. pH shift processing was found to be promising in the
      utilization of fish processing waste for the recovery of functional proteins from
      pangas processing waste thus by reducing the supply demand gap as well pollution
      problems.

PMID- 29450778
TI  - Exposure marker discovery of di(isononyl)cyclohexane-1,2-dicarboxylate using two
      mass spectrometry-based metabolite profiling data processing methods.
AB  - Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) is a plasticizer used in
      polyvinyl chloride (PVC) products, such as toys and food packaging. Because the
      use of DINCH is on the rise, the risk of human exposure to this chemical may
      likewise increase. Discovering markers for assessing human chemical exposure is
      difficult because the metabolism of chemicals within humans is complex. In this
      study, two mass spectrometry (MS)-based metabolite profiling data processing
      methods, the mass defect filter (MDF) method and the signal mining algorithm with
      isotope tracing (SMAIT) method, were used for DINCH metabolite discovery, and 110
      and 18 potential DINCH metabolite signal candidates were discovered,
      respectively, from in vitro DINCH incubation samples. Of these, the 21 signals
      were validated as tentative exposure marker signals in a rat model.
      Interestingly, the two methods generated rather different sets of DINCH exposure
      markers. Five of the 21 tentative exposure marker signals were verified as the
      probable DINCH structure-related metabolite signals based on their MS/MS product
      ion profiles. These five signals were detected in at least one human urine
      sample. Of the five probable DINCH structure-related metabolite signals, two
      novel signals might be suitable exposure markers that should be further
      investigated for their application in human DINCH exposure assessments. These
      observations indicate that the MDF and SMAIT methods may be used to discover a
      relatively different set of potential DINCH exposure markers.

PMID- 29450779
TI  - Effects of growth agents and mercury on several herbs.
AB  - The paper discussed the effects of growth agents and mercury on the growth of
      four herb species subjected to a pot experiment: Aloe vera, Setcreasea purpurea,
      Chlorophytum comosum, and Oxalis corniculata. We determined the height and
      biomass production of selected plants treated with different growth agents and
      different concentrations of mercury solutions. We evaluated the relative growth
      rate (RGR) of the experimental plants. The aim of the study was to explore
      potential novel solutions to the shortcoming of the low speed of
      phytoremediation. The results showed that the upper parts of Aloe vera and
      Chlorophytum comosum had the fastest growth in the treatment with water only. In
      contrast, the upper parts of Setcreasea purpurea grew most intensely after the
      treatment with Lvyebao Fertilizer, whereas the aboveground parts of Oxalis
      corniculata had the fastest growth after the application of water and the
      occasional use of Green Cake Fertilizer. In addition, the tolerance to mercury of
      Oxalis corniculata was the strongest, whereas that of Chlorophytum comosum was
      the lowest among the species investigated.

PMID- 29450780
TI  - Systematic Reviews and Meta-analysis in Rhinosinusitis: a Critical Review of the
      Reviews.
AB  - PURPOSE OF REVIEW: There has been an explosion in the number of published
      systematic reviews on chronic rhinosinusitis in the last decade. RECENT FINDINGS:
      While the aim of these reviews in facilitating evidence-based practice is
      laudable, poor quality reviews may contain significant bias that can mislead a
      non-discerning reader. Attention therefore must be given to review methodology
      before implanting findings. Organisations such as the Cochrane Collaboration
      promote high-quality reviews, but are limited in chronic sinus disease by
      heterogeneous outcomes and a paucity of randomised trials.

PMID- 29450781
TI  - Measuring Use of Evidence Based Psychotherapy for Posttraumatic Stress Disorder
      in a Large National Healthcare System.
AB  - To derive a method of identifying use of evidence-based psychotherapy (EBP) for
      post-traumatic stress disorder (PTSD), we used clinical note text from national
      Veterans Health Administration (VHA) medical records. Using natural language
      processing, we developed machine-learning algorithms to classify note text on a
      large scale in an observational study of Iraq and Afghanistan veterans with PTSD
      and one post-deployment psychotherapy visit by 8/5/15 (N = 255,968). PTSD visits
      were linked to 8.1 million psychotherapy notes. Annotators labeled 3467 randomly
      selected psychotherapy notes (kappa = 0.88) to indicate receipt of EBP. We met
      our performance targets of overall classification accuracy (0.92); 20.2% of
      veterans received >= one session of EBP over the study period. Our method can
      assist with identifying EBP use and studying EBP-associated outcomes in routine
      clinical practice.

PMID- 29450782
TI  - [Is the refusal of invasive or noninvasive ventilation in a child with spinal
      muscular atrophy ethically justified?]
AB  - We report about an infant who was diagnosed with spinal muscular atrophy type 1
      (Werdnig-Hoffmann) at the age of 7 weeks. In a detailed discussion with the
      physicians the parents decided against mechanical ventilation in the event of
      either acute or chronical respiratory failure. During care at home all palliative
      actions were taken to optimize the quality of life for the child. The boy died at
      the age of 7 months at home. Whether continuous mechanical ventilation in a child
      with spinal muscular atrophy type 1 should be the individual decision of the
      parents or whether it should never be offered by the physicians is discussed
      controversially in the present medical literature.

PMID- 29450783
TI  - [Laryngospasm in amyotrophic lateral sclerosis : A case report].
AB  - Laryngospasm in amyotrophic lateral sclerosis is a symptom seldom described in
      neurological literature. Despite the self limiting character it means a life
      threatening condition for the patient himself. This case report and the following
      discussion tries to look upon underlying causes and options of therapy.

PMID- 29450784
TI  - [A challenging decision-making-process pro or con surgical heart valve
      replacement in a case of long-term non-adherence : A case report].
AB  - A young, still multimorbid woman aquires infectious endocarditis. Anamnestically
      severe non-adherence concerning medical advice is reported. Complete cure may
      only be achieved by performing surgical heart valve replacement, which implies
      lifelong scrupulous oral anticoagulation postoperatively. Discussion evolves
      within medical staff, whether surgery should be indicated or not.

PMID- 29450787
TI  - A case of small intestinal neuroendocrine carcinoma diagnosed using double
      balloon endoscopy with long-term survival.
AB  - Neuroendocrine neoplasms, including neuroendocrine tumors (NETs) and
      neuroendocrine carcinomas (NECs), are rare epithelial tumors with a predominant
      neuroendocrine differentiation. Compared with NETs, NECs have been reported to be
      rarer and have a poorer prognosis. We present a rare case of small bowel NEC
      diagnosed using double-balloon endoscopy (DBE) and the long-term survival
      accomplished via intensive therapy. DBE revealed an ulcerative tumor in the deep
      jejunum, and biopsy specimens showed large and highly dysplastic tumor cells;
      immuno-histological synaptophysin and chromogranin A tests were positive, and the
      Ki-67 index was more than 90%. Partial intestinal resection without complete
      lymph node dissection was performed and, postoperatively, chemotherapy was
      administered. The patient was observed for 3 years after chemotherapy, and
      complete remission was maintained.

PMID- 29450788
TI  - Tool use in Goffin's cockatoos: Shape/frame matching.
AB  - Nonhuman tool use is no longer questioned; the issues now are whether such use is
      mostly inflexible and innately specified or involves experience, innovation,
      adaptation, and cognitive planning, and how many species qualify. Habl and
      Auersperg (PLoS One, 12(11):e0186859, 2017) have shown that some Goffin's
      cockatoos (Cacatua goffiniana) respond in novel ways to a tool-use task that
      nonhuman primates and young children find somewhat challenging.

PMID- 29450789
TI  - Control by association: Transfer of implicitly primed attentional states across
      linked stimuli.
AB  - Although cognitive control has traditionally been viewed in opposition to
      associative learning, recent studies show that people can learn to link
      particular stimuli with specific cognitive control states (e.g., high attentional
      selectivity). Here, we tested whether such learned stimulus-control associations
      can transfer across paired-associates. In the Stimulus-Stimulus (S-S) Association
      phase, specific face or house images repeatedly preceded the presentation of
      particular scene stimuli, creating paired face/house-scene associates in memory.
      The Stimulus-Control (S-C) Association phase then associated these scenes with
      different attentional control states by probabilistically biasing specific scenes
      to mostly precede either congruent or incongruent trials in a Stroop task.
      Finally, in the Stimulus-Control Transfer (S-CT) phase, the faces and houses from
      the S-S phase preceded Stroop trials but were not predictive of congruency,
      testing whether stimulus-control associations would transfer from scenes to their
      associated face/house stimuli. In Experiments 1 and 3, we found that learned
      implicit stimulus-control associations could transfer across closely linked cues,
      and in Experiment 2, we showed that this transfer depended on the memory
      associations formed in the S-S phase. While this form of transfer learning has
      previously been demonstrated for stimulus-reward associations, the present study
      provides the first evidence for the associative transfer of stimulus-control
      associations across arbitrarily linked stimuli. This work demonstrates how people
      can learn to implicitly adapt their processing strategies in a flexible context
      dependent manner and establishes a novel learning mechanism supporting the
      generalization of cognitive control.

PMID- 29450790
TI  - Editorial: Bayesian methods for advancing psychological science.

PMID- 29450785
TI  - The role of the alternative pathway of complement activation in glomerular
      diseases.
AB  - The complement system (CS) has recently been recognized as a bridge between
      innate and adaptive immunity that constitutes a very complex mechanism
      controlling the clearance of pathogens, cellular debris, and immune complexes.
      Out of three known pathways of complement activation, the alternative pathway
      (AP) plays a critical role in host defense by amplifying the complement response,
      independently of initiation pathway and continuously maintaining low-level
      activity in a process called 'thick-over.' A key molecule of the CS is C3, in
      which the AP is constantly activated. To prevent host cell destruction, a group
      of the AP regulators tightly controls this pathway of the CS activation. Acquired
      and genetic abnormalities of the CS may alter the delicate balance between
      enhancing and inhibiting the AP cascade. These can lead to the uncontrolled CS
      activation, inflammatory response, and subsequent tissue damage. Since complement
      components are locally produced and activated in the kidney, the abnormalities
      targeting the AP may cause glomerular injury. C3 glomerulopathy is a new entity,
      in which the AP dysregulation has been well established. However, recent studies
      indicate that the AP may also contribute to a wide range of kidney pathologies,
      including immune-complex-mediated glomerulonephritis (GN), pauci-immune GN, and
      primary membranous nephropathy (PMN). This article provides insight into current
      knowledge on the role of the AP in the pathogenesis of glomerular diseases,
      focusing mainly on various types of primary and secondary GN and PMN.

PMID- 29450791
TI  - Face processing skills predict faithfulness of portraits drawn by novices.
AB  - Individuals show astonishing variability in their face recognition abilities, and
      the causes and consequences of this heterogeneity are unclear. Special expertise
      with faces, for example in portraitists, is associated with advantages on face
      processing tasks, especially those involving perceptual abilities. Do face
      processing skills improve through practice, or does drawing skill reflect pre
      existing individual differences? If the latter, then the association between face
      processing skills and production of faithful portraits should also exist in
      people without practice in drawing. Two exploratory studies and one follow-up
      confirmatory study provide support for this hypothesis. Drawing ability of
      novices was predicted by their performance on face recognition tasks involving
      perceptual discrimination and visual short-term memory, but not by those that
      rely more heavily on long-term memory or memory for non-face objects. By
      examining non-experts, we show that expertise with faces might build upon pre
      existing individual differences in face processing skills.

PMID- 29450792
TI  - Examination of long-term visual memorization capacity in the Clark's nutcracker
      (Nucifraga columbiana).
AB  - Clark's nutcrackers exhibit remarkable cache recovery behavior, remembering
      thousands of seed locations over the winter. No direct laboratory test of their
      visual memory capacity, however, has yet been performed. Here, two nutcrackers
      were tested in an operant procedure used to measure different species' visual
      memory capacities. The nutcrackers were incrementally tested with an ever
      expanding pool of pictorial stimuli in a two-alternative discrimination task.
      Each picture was randomly assigned to either a right or a left choice response,
      forcing the nutcrackers to memorize each picture-response association. The
      nutcrackers' visual memorization capacity was estimated at a little over 500
      pictures, and the testing suggested effects of primacy, recency, and memory decay
      over time. The size of this long-term visual memory was less than the
      approximately 800-picture capacity established for pigeons. These results support
      the hypothesis that nutcrackers' spatial memory is a specialized adaptation tied
      to their natural history of food-caching and recovery, and not to a larger long
      term, general memory capacity. Furthermore, despite millennia of separate and
      divergent evolution, the mechanisms of visual information retention seem to
      reflect common memory systems of differing capacities across the different
      species tested in this design.

PMID- 29450793
TI  - The Quality of Response Time Data Inference: A Blinded, Collaborative Assessment
      of the Validity of Cognitive Models.
AB  - Most data analyses rely on models. To complement statistical models,
      psychologists have developed cognitive models, which translate observed variables
      into psychologically interesting constructs. Response time models, in particular,
      assume that response time and accuracy are the observed expression of latent
      variables including 1) ease of processing, 2) response caution, 3) response bias,
      and 4) non-decision time. Inferences about these psychological factors hinge upon
      the validity of the models' parameters. Here, we use a blinded, collaborative
      approach to assess the validity of such model-based inferences. Seventeen teams
      of researchers analyzed the same 14 data sets. In each of these two-condition
      data sets, we manipulated properties of participants' behavior in a two
      alternative forced choice task. The contributing teams were blind to the
      manipulations, and had to infer what aspect of behavior was changed using their
      method of choice. The contributors chose to employ a variety of models,
      estimation methods, and inference procedures. Our results show that, although
      conclusions were similar across different methods, these "modeler's degrees of
      freedom" did affect their inferences. Interestingly, many of the simpler
      approaches yielded as robust and accurate inferences as the more complex methods.
      We recommend that, in general, cognitive models become a typical analysis tool
      for response time data. In particular, we argue that the simpler models and
      procedures are sufficient for standard experimental designs. We finish by
      outlining situations in which more complicated models and methods may be
      necessary, and discuss potential pitfalls when interpreting the output from
      response time models.

PMID- 29450794
TI  - Association Between Obstetric Provider's Advice and Gestational Weight Gain.
AB  - Objective This study examined associations between pregnant women's report of
      obstetric provider GWG advice, self-reported adherence to such advice, and GWG.
      Methods Healthy pregnant women (N = 91) who started obstetric care prior to 17
      weeks of gestation completed assessments between 30 and 34 weeks of gestation.
      These included survey (questions on receipt of and adherence to provider GWG
      advice, and demographics) and anthropometric measures. GWG data were abstracted
      from electronic health records. Analyses included Chi square and Mann-Whitney
      tests, and binary and multivariate logistic regressions. Results The cohort's
      median age was 28 years, 68% of women were White, 78% had a college education,
      50.5% were overweight or obese before the pregnancy, and 62.6% had GWGs above the
      Institute of Medicine-recommended ranges. Sixty-seven percent of women reported
      having received GWG advice from their obstetric providers and, of those, 54.1%
      reported that they followed their provider's advice. Controlling for race,
      education and pre-pregnancy BMI, receipt of GWG advice was marginally associated
      with increased odds of excessive weight gain (OR 2.52, CI 0.89-7.16). However,
      women that reported following the advice had lower odds of excessive GWG (OR
      0.18, CI 0.03-0.91) and, on average, gained 11.3 pounds less than those who
      reported following the advice somewhat or not at all. Conclusions Frequency of
      GWG advice from obstetric providers is less than optimal. When given and
      followed, provider advice may reduce the risk of excessive GWG. Research to
      understand factors that facilitate providers GWG advice giving and women's
      adherence to providers' advice, and to develop interventions to optimize both, is
      needed.

PMID- 29450795
TI  - Ethics and Confidentiality for Psychologists in Academic Health Centers.
AB  - Psychologists in academic health centers (AHC) face important ethical issues
      including confidentiality when working with a multidisciplinary team, sharing of
      information through the electronic health record, obtaining informed consent in a
      fast-paced healthcare environment, cultural competency in the medical setting,
      and issues related to supervision and training. The goal of this paper is to
      describe ethical issues for psychologists in AHCs in the context of case
      examples, and to consider ethical decision-making tools to enhance clinical care.
      Considerations for best practices in integrated care settings will be discussed,
      and the APA Ethical Standards will be referenced throughout.

PMID- 29450796
TI  - Prospective Comparison of the Minnesota Multiphasic Personality Inventory-2 (MMPI
      2) and MMPI-2-Restructured Form (MMPI-2-RF) in Predicting Treatment Outcomes
      Among Patients with Chronic Low Back Pain.
AB  - The purpose of the current study was to examine the relative utility of the most
      updated MMPI adult instrument, the Minnesota Multiphasic Personality Inventory-2
      Restructured Form (MMPI-2-RF), which was designed to address psychometric
      limitations of the MMPI-2. To this end, we compared mean scores and correlates of
      emotional distress treatment outcomes using the Depression Anxiety Stress Scales
      in a sample of 230 patients (73 males, 157 females) who had completed an
      interdisciplinary chronic pain rehabilitation program. Structural equation
      modeling analyses indicated that higher scale scores from all the MMPI-2-RF
      substantive domains were meaningfully associated with worse emotional distress
      outcomes, whereas the MMPI-2 Clinical Scales generally did not have any
      meaningful associations. Similar results were found in additional analyses using
      a clinically significant change framework with more direct clinical implications.
      The results of this study provide preliminary support for the use of the MMPI-2
      RF among patients with chronic low back pain.

PMID- 29450797
TI  - Cultural Considerations for Psychologists in Primary Care.
AB  - Many health concerns in the United States (e.g., diabetes) are routinely managed
      in primary care settings. Regardless of the medical condition, patients' health
      is directly influenced by factors such as healthcare providers and cultural
      background. Training related to how behaviors influence health, coupled with
      training on how cultural diversity intersects with mental health, allows
      psychologists to have the relevant expertise to assist in the development of
      primary care behavioral health interventions. However, many psychologists in
      primary care struggle with how to integrate a culture-centered paradigm into
      their roles as behavioral health providers. This paper provides an introduction
      on how three culture-centered concepts (providers' cultural sensitivity, patient
      provider cultural congruency, and patients' health literacy) can be applied in
      primary care using the Five A's Organizational Construct and a model of cultural
      competence. In addition, the paper includes a section on integration of cultural
      considerations into consultation and training and concludes with a discussion of
      how the three culture-centered concepts have implications for health equity.

PMID- 29450799
TI  - Iron oxide labeling does not affect differentiation potential of human bone
      marrow mesenchymal stem cells exhibited by their differentiation into cardiac and
      neuronal cells.
AB  - Mesenchymal stem cells (MSCs) have shown promising outcomes in cardiac and
      neuronal diseases. Efficient and noninvasive tracking of MSCs is essential to
      harness their therapeutic potential. Iron oxide nanoparticles (IONPs) have
      emerged as effective means to label stem cells and visualize them using magnetic
      resonance imaging (MRI). It is known that IONPs do not affect viability and cell
      proliferation of stem cells. However, very few studies have demonstrated
      differentiation potential of iron oxide-labeled MSCs and their differentiation
      into specific lineages that can contribute to cellular therapies. The
      differentiation of IONP-labeled human bone marrow mesenchymal stem cells (hBM
      MSCs) into cardiac and neuronal lineages has never been studied. In this study,
      we have shown that IONP-labeled hBM-MSCs retain their differentiation potential
      to cardiac and neuronal cell lineages. We also confirmed that labeling hBM-MSCs
      with IONP does not affect their characteristic properties such as viability,
      cellular proliferation rate, surface marker profiling, and trilineage
      differentiation capacity. This study shows that IONP can be efficiently tracked,
      and its labeling does not alter stemness and differentiation potential of hBM
      MSCs. Thus, the labeled hBM-MSCs can be used in clinical therapies and
      regenerative medicine.

PMID- 29450798
TI  - Catastrophizing, Acceptance, and Coping as Mediators Between Pain and Emotional
      Distress and Disability in Fibromyalgia.
AB  - Catastrophizing, acceptance, and coping have an important predictive value in
      chronic pain; however, it is not known which of these variables has the greatest
      contribution in fibromyalgia (FM). This study explored the mediating role of
      catastrophizing, acceptance, and coping in the relationship between pain and
      emotional distress/disability in a FM sample. Ninety-two FM patients and 51
      healthy participants controls were evaluated on pain- and psychological-related
      variables. Catastrophizing, acceptance, behavioral coping, and emotional coping
      were significantly correlated with emotional distress and/or disability.
      Catastrophizing had a significant effect as a mediator on the relationship
      between pain and depression/anxiety. The current management of FM could improve
      by including cognitive techniques aimed at modifying the negative appraisal of
      pain.

PMID- 29450800
TI  - The endogenous subcellular localisations of the long chain fatty acid-activating
      enzymes ACSL3 and ACSL4 in sarcoma and breast cancer cells.
AB  - Fatty acid uptake and metabolism are often dysregulated in cancer cells. Fatty
      acid activation is a critical step that allows these biomolecules to enter
      cellular metabolic pathways such as mitochondrial beta-oxidation for ATP
      generation or the lipogenic routes that generate bioactive lipids such as the
      inositol phospholipids. Fatty acid activation by the addition of coenzyme A is
      catalysed by a family of enzymes called the acyl CoA synthetase ligases (ACSL).
      Furthermore, enhanced expression of particular ACSL isoforms, such as ACSL4, is a
      feature of some more aggressive cancers and may contribute to the oncogenic
      phenotype. This study focuses on ACSL3 and ACSL4, closely related structural
      homologues that preferentially activate palmitate and arachidonate fatty acids,
      respectively. In this study, immunohistochemical screening of multiple soft
      tissue tumour arrays revealed that ACSL3 and ACSL4 were highly, but
      differentially, expressed in a subset of leiomyosarcomas, fibrosarcomas and
      rhabdomyosarcomas, with consistent cytoplasmic and granular stainings of tumour
      cells. The intracellular localisations of endogenously expressed ACSL3 and ACSL4
      were further investigated by detailed subcellular fractionation analyses of
      HT1080 fibrosarcoma and MCF-7 breast cancer cells. ACSL3 distribution closely
      overlapped with proteins involved in trafficking from the trans-Golgi network and
      endosomes. In contrast, the ACSL4 localisation pattern more closely followed that
      of calnexin which is an  endoplasmic reticulum resident chaperone. Confocal
      immunofluorescence imaging of MCF-7 cells confirmed the intracellular
      localisations of both enzymes. These observations reveal new information
      regarding the compartmentation of fatty acid metabolism in cancer cells.

PMID- 29450801
TI  - Enhancement of pain inhibition by working memory with anodal transcranial direct
      current stimulation of the left dorsolateral prefrontal cortex.
AB  - The aim of this study was to examine whether transcranial direct current
      stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) enhances pain
      inhibition by improving working memory (WM). Forty healthy volunteers
      participated in two tDCS sessions. Pain was evoked by electrical stimulation at
      the ankle. Participants performed an n-back task (0-back and 2-back). The
      experimental protocol comprised five counterbalanced conditions (0-back, 2-back,
      pain, 0-back with pain and 2-back with pain) that were performed twice (pre-tDCS
      baseline and during tDCS). Compared with the pre-tDCS baseline values, anodal
      tDCS decreased response times for the 2-back condition (p < 0.01) but not for the
      0-back condition (p > 0.5). Anodal tDCS also decreased pain ratings marginally in
      the 2-back with pain condition, but not the 0-back with pain condition (p = 0.052
      and p > 0.2, respectively). No effect was produced by sham tDCS for any condition
      (p > 0.2). These results indicate that tDCS of the left DLPFC may enhance pain
      inhibition by improving WM.

PMID- 29450802
TI  - MHI-148 Cyanine Dye Conjugated Chitosan Nanomicelle with NIR Light-Trigger
      Release Property as Cancer Targeting Theranostic Agent.
AB  - PURPOSE: Paclitaxel (PTX) loaded hydrophobically modified glycol chitosan (HGC)
      micelle is biocompatible in nature, but it requires cancer targeting ability and
      stimuli release property for better efficiency. To improve tumor retention and
      drug release characteristic of HGC-PTX nanomicelles, we conjugated cancer
      targeting heptamethine dye, MHI-148, which acts as an optical imaging agent,
      targeting moiety and also trigger on-demand drug release on application of NIR
      808 nm laser. PROCEDURES: The amine group of glycol chitosan modified with
      hydrophobic 5beta-cholanic acid and the carboxyl group of MHI-148 were bonded by
      1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide chemistry.
      Paclitaxel was loaded to MHI-HGC nanomicelle by an oil-in-water emulsion method,
      thereby forming MHI-HGC-PTX. RESULTS: Comparison of near infrared (NIR) dyes, MHI
      148, and Flamma-774 conjugated to HGC showed higher accumulation for MHI-HGC in
      4T1 tumor and 4T1 tumor spheroid. In vitro studies showed high accumulation of
      MHI-HGC-PTX in 4T1 and SCC7 cancer cell lines compared to NIH3T3 cell line. In
      vivo fluorescence imaging of the 4T1 and SCC7 tumor showed peak accumulation of
      MHI-HGC-PTX at day 1 and elimination from the body at day 6. MHI-HGC-PTX showed
      good photothermal heating ability (50.3  degrees C), even at a low concentration
      of 33 MUg/ml in 1 W/cm2 808 nm laser at 1 min time point. Tumor reduction studies
      in BALB/c nude mice with SCC7 tumor showed marked reduction in MHI-HGC-PTX in the
      PTT group combined with photothermal therapy compared to MHI-HGC-PTX in the group
      without PTT. CONCLUSION: MHI-HGC-PTX is a cancer theranostic agent with cancer
      targeting and optical imaging capability. Our studies also showed that it has
      cancer targeting property independent of tumor type and tumor reduction property
      by combined photothermal and chemotherapeutic effects.

PMID- 29450803
TI  - A rare case of acute presentation of trocar site hernia from robot-assisted
      laparoscopic partial nephrectomy.
AB  - Trocar site hernia is not a common acute complication encountered after robot
      assisted surgery, especially in the urological cohort of patients. A few case
      reports of small bowel obstruction secondary to incarceration by trocar site
      hernia have been described in gynaecological surgery and prostatectomies. As the
      clinical presentation is non-specific, late diagnosis has significant implication
      on morbidity and mortality. Here, we present a rare case of a patient with recent
      robot-assisted laparoscopic partial nephrectomy for a renal cell carcinoma
      presented with features of impending bowel obstruction secondary to incarcerated
      small bowel in the trocar site. We also reviewed the literature focusing on
      clinical features of trocar site hernia and preventive measures.

PMID- 29450805
TI  - pH-responsive CAP-co-poly(methacrylic acid)-based hydrogel as an efficient
      platform for controlled gastrointestinal delivery: fabrication, characterization,
      in vitro and in vivo toxicity evaluation.
AB  - Cellulose acetate phthalate-based pH-responsive hydrogel was synthesized for
      fabrication of polymeric matrix tablets for gastro-protective delivery of
      loxoprofen sodium. Cellulose acetate phthalate (CAP) was cross-linked with
      methacrylic acid (MAA) using free radical polymerization technique. Fourier
      transform infrared (FTIR) spectra confirmed the formation of cross-linked
      structure of CAP-co-poly(methacrylic acid). Thermogravimetric analysis (TGA) and
      differential scanning calorimetry (DSC) confirmed the thermal stability of
      polymeric networks, and scanning electron microscopy (SEM) and energy-dispersive
      X-ray spectrum (EDS) images unveiled that the prepared formulations were porous
      in nature and thus the developed formulations had shown better diffusibility.
      Swelling and in vitro drug release was performed at various pHs and maximum
      swelling and release was obtained at pH 7.4, while swelling and release rate was
      very low at pH 1.2 which confirmed the pH-responsive behavior of CAP-co
      poly(MAA). CAP-co-poly(MAA) copolymer prevents the release of loxoprofen sodium
      into the stomach due to reduced swelling at gastric pH while showing significant
      swelling and drug release in the colon. Cytotoxicity studies revealed higher
      biocompatibility of fabricated hydrogel. Acute oral toxicity studies were
      performed for the evaluation and preliminary screening of safety profile of the
      developed hydrogels. Matrix tablets were evaluated for release behavior at
      simulated body pH. The investigations performed for analysis of hydrogels and
      fabricated matrix tablets indicated the controlled drug release and gastro
      protective drug delivery of CAP-co-poly(MAA) hydrogels and pH-sensitive matrix
      tablets for targeted delivery of gastro-sensitive/irritative agents. Graphical
      abstract ?.

PMID- 29450804
TI  - Long-Term Development of Embryonic Cerebellar Grafts in Two Strains of Lurcher
      Mice.
AB  - For many degenerative cerebellar diseases, currently, no effective treatment that
      would substantially restore cerebellar functions is available.
      Neurotransplantation could be a promising therapy for such cases. Nevertheless,
      there are still severe limitations for routine clinical use. The aim of the work
      was to assess volume and morphology and functional impact on motor skills of an
      embryonic cerebellar graft injected in the form of cell suspension in Lurcher
      mutant and wild-type mice of the B6CBA and C3H strains after a 6-month survival
      period. The grafts survived in the majority of the mice. In both B6CBA and C3H
      Lurcher mice, most of the grafts were strictly delimited with no tendency to
      invade the host cerebellum, while in wild-type mice, graft-derived Purkinje cells
      colonized the host's cerebellum. In C3H Lurcher mice, but not in B6CBA Lurchers,
      the grafts had smaller volume than in their wild-type counterparts. C3H wild-type
      mice had significantly larger grafts than B6CBA wild-type mice. No positive
      effect of the transplantation on performance in the rotarod test was observed.
      The findings suggest that the niche of the Lurcher mutant cerebellum has a
      negative impact on integration of grafted cells. This factor seems to be limiting
      for specific functional effects of the transplantation therapy in this mouse
      model of cerebellar degeneration.

PMID- 29450807
TI  - An Eye Fixation-Related Potential Study in Two Reading Tasks: Reading to Memorize
      and Reading to Make a Decision.
AB  - We investigated how two different reading tasks, namely reading to memorize [Read
      & Memorize (RM)] and reading to decide whether a text was relevant to a given
      topic [Read & Decide (RD)], modulated both eye movements (EM) and brain activity.
      To this end, we set up an ecological paradigm using the eye fixation-related
      potentials (EFRP) technique, in which participants freely moved their eyes to
      process short paragraphs, while their electroencephalography (EEG) activity was
      recorded in synchronization with their EM. A general linear model was used to
      estimate at best EFRP, taking account of the overlap between adjacent potentials,
      and more precisely with the potential elicited at text onset, as well as saccadic
      potentials. Our results showed that EM patterns were top-down modulated by
      different task demands. More interestingly, in both tasks, we observed slow-wave
      potentials that gradually increased across the first eye fixations. These slow
      waves were larger in the RD task than in the RM task, specifically over the left
      hemisphere. These results suggest that the decision-making process during reading
      in the RD task engendered a greater memory load in working memory than that
      generated in a classic reading task. The significance of these findings is
      discussed in the light of recent theories and models of working memory
      processing.

PMID- 29450806
TI  - Dissolution and oral bioavailability enhancement of praziquantel by solid
      dispersions.
AB  - The aim of the present investigation was to enhance the solubility, dissolution,
      and oral bioavailability of praziquantel (PZQ), a poorly water-soluble BCS II
      drug (Biopharmaceutical Classification System), using a solid dispersion (SD)
      technique involving hydrophilic copolymers. The SD formulations were prepared by
      a solvent evaporation method with PZQ and PEG 4000 (polyethylene glycol 4000),
      PEG 6000, or P 188 polymers at various weight ratios or a combination of PEG
      4000/P 188. The optimized SD formulation, which had the highest solubility in
      distilled water, was further characterized by its surface morphology,
      crystallinity, and dissolution in 0.1 M HCl with 0.2% w/v of sodium dodecyl
      sulfate (SDS). X-ray diffraction (XRD) and Fourier transform infrared
      spectroscopy (FTIR) revealed the amorphous form of PZQ in the SDs. Moreover, at
      an oral dosage of 5 mg/kg PZQ, the SDs had higher Cmax values and areas under the
      curve (AUCs) compared to those of commercial PZQ tablets. Preparation of PZQ
      loaded SDs using PEG 4000/P 188 is a promising strategy to improve the oral
      bioavailability of PZQ.

PMID- 29450808
TI  - Localizing Event-Related Potentials Using Multi-source Minimum Variance
      Beamformers: A Validation Study.
AB  - Adaptive and non-adaptive beamformers have become a prominent neuroimaging tool
      for localizing neural sources of electroencephalographic (EEG) and
      magnetoencephalographic (MEG) data. In this study, we investigated single-source
      and multi-source scalar beamformers with respect to their performances in
      localizing and reconstructing source activity for simulated and real EEG data. We
      compared a new multi-source search approach (multi-step iterative approach; MIA)
      to our previous multi-source search approach (single-step iterative approach;
      SIA) and a single-source search approach (single-step peak approach; SPA). In
      order to compare performances across these beamformer approaches, we manipulated
      various simulated source parameters, such as the amount of signal-to-noise ratio
      (0.1-0.9), inter-source correlations (0.3-0.9), number of simultaneously active
      sources (2-8), and source locations. Results showed that localization performance
      followed the order of MIA > SIA > SPA regardless of the number of sources, source
      correlations, and single-to-noise ratios. In addition, SIA and MIA were
      significantly better than SPA at localizing four or more sources. Moreover, MIA
      was better than SIA and SPA at identifying the true source locations when signal
      characteristics were at their poorest. Source waveform reconstructions were
      similar between MIA and SIA but were significantly better than that for SPA. A
      similar trend was also found when applying these beamformer approaches to a real
      EEG dataset. Based on our findings, we conclude that multi-source beamformers
      (MIA and SIA) are an improvement over single-source beamformers for localizing
      EEG. Importantly, our new search method, MIA, had better localization
      performance, localization precision, and source waveform reconstruction as
      compared to SIA or SPA. We therefore recommend its use for improved source
      localization and waveform reconstruction of event-related potentials.

PMID- 29450809
TI  - Model diagnostics for the proportional hazards model with length-biased data.
AB  - Length-biased data are frequently encountered in prevalent cohort studies. Many
      statistical methods have been developed to estimate the covariate effects on the
      survival outcomes arising from such data while properly adjusting for length
      biased sampling. Among them, regression methods based on the proportional hazards
      model have been widely adopted. However, little work has focused on checking the
      proportional hazards model assumptions with length-biased data, which is
      essential to ensure the validity of inference. In this article, we propose a
      statistical tool for testing the assumed functional form of covariates and the
      proportional hazards assumption graphically and analytically under the setting of
      length-biased sampling, through a general class of multiparameter stochastic
      processes. The finite sample performance is examined through simulation studies,
      and the proposed methods are illustrated with the data from a cohort study of
      dementia in Canada.

PMID- 29450810
TI  - Characterisation of a new species of Trichodorus Cobb, 1913 (Triplonchida:
      Trichodoridae) from Iran based on morphological and molecular data.
AB  - Trichodorus zanjanensis n. sp., collected from the rhizosphere of wild almond
      tree (Amygdalus scoparia Spach) in Zanjan Province, Iran, is described and
      illustrated based on morphological and molecular data. The new species is
      characterised by its body length (772-819 MUm in males; 704-953 MUm in females),
      and in having medium-sized onchiostyle (60-64 MUm in males; 59-65 MUm in females)
      and a short dorsal overlap of the intestine. Males of the new species have two
      ventromedian cervical papillae posterior to onchiostyle region, ventrally curved
      spicules, smooth, long and wide manubrium, gradually continuing in a narrower
      anterior part of the blade provided with bristles and marked from the wider and
      transversely striated main part of the blade, tapered towards distal end, three
      ventromedian precloacal supplements, the posterior one (SP1) situated at the
      level of anterior blade and gubernaculum situated at 24-25 MUm from the cloaca.
      Females have one pair of sublateral body pores in the vulva region, medium
      rounded triangular to oval sclerotised vaginal pieces in lateral view, and pear
      shaped vagina. The new species resembles T. persicus De Waele & Sturhan, 1987, T.
      minzi De Waele & Cohn, 1992 and T. taylori De Waele, Mancini, Roca & Lamberti,
      1982. The results of morphological and morphometric comparisons and molecular
      data based on sequences of the partial 18S and D2-D3 expansion segments of 28S
      rRNA genes, clearly separated T. zanjanensis n. sp. from these known species and
      supported the description of T. zanjanensis n. sp. as a new species.

PMID- 29450811
TI  - Debulking surgery of pituitary adenoma as a strategy to facilitate definitive
      stereotactic radiosurgery.
AB  - In patients with pituitary adenomas (PA) who are unable to undergo complete
      surgical resection, radiation therapy (RT), specifically stereotactic
      radiosurgery (SRS), results in excellent local control. However, the utility of
      radiosurgery may be limited by the proximity of the lesion to the optic chiasm
      (OC). We evaluate the efficacy of debulking surgery in increasing the PA-OC
      separation to convert patients into SRS candidates. From 2007 to 2015, 31
      patients with PA < 2 mm from the OC underwent debulking surgery followed by RT
      within 2 years of resection. Coronal and sagittal T1-pre- and post-contrast
      sequences were used to determine PA-OC separation. Time interval between
      postoperative and pre-radiotherapy MRI scans and type of radiation therapy were
      analyzed. Functional tumor status, tumor characteristics [cavernous sinus (CS) or
      suprasellar (SS) involvement, chiasm/nerve encasement (NE)], and presence of >= 2
      of these characteristics (multiple factors, MF) was also noted. Surgery converted
      9 of 31 patients (29%) to SRS candidates. Median time from surgery to pre-RT
      planning MRI was 8 months (range 2-20). Of the 31 patients initially ineligible
      for SRS, 6 became eligible immediately after surgery, and another 3 were deemed
      eligible on follow-up. Mean PA-OC separation was 0.3 mm preoperative, 1.4 mm
      postoperative, and 2.1 mm at time of SRS (p = 0.002). Preoperative SS, NE, and MF
      involvement predicted pre-RT separation < 2 mm. Debulking surgery of unresectable
      pituitary tumors is a successful strategy for converting select radiosurgery
      ineligible patients to radiosurgery candidates. Absence of preoperative SS, NE,
      and MF predicts for successful conversion.

PMID- 29450814
TI  - Improving the Catalytic Activity and Thermostability of MAS1 Lipase by Alanine
      Substitution.
AB  - MAS1 is a lipase isolated from Streptomyces sp. strain W007 with potential
      application in biotechnology. Structural analysis of MAS1 lipase showed that
      eight amino acids with bulkier side located in the substrate-binding pocket may
      be involved in affecting catalytic performance. Alanine substitutions of those
      residues were conducted to reduce steric clash of catalyzed pocket and probe
      their functional roles. The kcat/Km of mutants H108A, F153A, and V233A increased
      to 2.3-, 2.1-, and 1.4-fold, respectively. Interestingly, the half-life (60 
      degrees C) of F153A had shifted to 523 min after mutagenesis, which was fivefold
      enhancement toward that of MAS1 wide-type. Furthermore, higher hydrolysis ability
      of mutants H108A and F153A toward palm stearin of high melting temperature made
      them potentially applicable in oil/fat modification. Our work provided an example
      to obtain biocatalysts with desired catalytic behaviors by protein engineering.

PMID- 29450813
TI  - Memory Rehabilitation in Patients with Epilepsy: a Systematic Review.
AB  - Memory failure is a common clinical concern of patients with epilepsy and is
      associated with significant functional impairments. Thus, memory rehabilitation
      is of critical clinical importance. In this article, we aimed to systematically
      evaluate the efficacy of memory rehabilitation in patients with epilepsy. The
      Preferred Items for Systematic Reviews and Meta-Analyses (PRISMA) was used to
      guide searches, extraction and reporting of data in this review. PsycINFO,
      Medline and PsychBITE searches yielded 95 studies. Twelve papers met inclusion
      criteria, reporting outcomes of cognitive or behavioural interventions that
      specifically targeted the rehabilitation of memory in patients with epilepsy.
      Methodological rigour was rated using the Single-Case Experimental Design (SCED)
      scale for single-case studies and a modified version of the Downs and Black
      checklist for group studies. Twelve prospective studies, nine group (six pre-post
      design, one waitlist crossover, two randomised controlled trials) and three
      single-case studies were identified. Eleven of the studies included adults, eight
      of which involved adults with temporal lobe epilepsy (TLE). One paediatric study
      was identified. The quality of group studies ranged from 36% (poor) to 72%
      (good), using the modified Downs and Black checklist. Single-case studies were
      assessed using the SCED scale and assessed to range in quality from four to seven
      out to 11. Overall, memory rehabilitation was associated with improved memory
      function in all studies. Verbal memory outcomes were most commonly examined and
      associated with improvements. This review found that the level of evidence
      available to support rehabilitation of memory in patients with epilepsy was
      generally weak and inconsistent. Nevertheless, studies conducted to date, albeit
      of limited methodological quality, offer preliminary evidence that memory
      rehabilitation is associated with improvements in verbal memory in patients with
      temporal lobe epilepsy. Little is known about the efficacy of memory
      rehabilitation in patients with non-TLE, children, and other aspects of memory
      difficulties. Guidelines for future research are proposed.

PMID- 29450815
TI  - Factors affecting reproductive performance in dromedary camel herds in Saudi
      Arabia.
AB  - A survey of 7122 dromedary camels in 115 herds in Saudi Arabia was used to
      estimate the effects of herd size (HZ; < 25 vs. 25-49 vs. 50-100 vs. > 100
      camels), herder/camels ratio (H/C; 1:< 25 vs. 1:25-50 vs. 1:> 50), manager
      experience (ME; < 5 vs. 5-10 vs. > 10 years), male/females ratio (M/F), housing
      system (HS; free vs. closed vs. mixed), length of the breeding season (winter vs.
      winter and spring vs. fall, winter and spring), age at first mating (3 vs. > 3
      years), and time of mating after parturition (<= 3 vs. > 3 months) and their
      interactions on the overall pregnancy rate. Barren females of these herds (n =
      886) were examined for the causes of infertility. Results showed that herds with
      H/C of 1:< 25 had higher overall pregnancy rate (95.29%) than herds with H/C of
      1:25-50 (79.84%) and those with H/C of 1:> 50 (72.79%) (p = 0.003). Herds having
      ME of > 10 years revealed greater overall pregnancy rate (94.89%) than herds with
      ME of 5-10 years (80.54%) and those with ME of < 5 years (72.5%) (p = 0.001).
      There were significant interactions between H/C * HZ (p = 0.003), H/C * HS (p =
      0.006), and ME * HS (p = 0.02). The overall pregnancy rate did not significantly
      differ between herds bred females by age of 3 years and those bred females by age
      > 3 years and in females bred within 3 months after parturition and in those bred
      after 3 months. The mean calving interval was shorter (p = 0.008) in camels mated
      within 3 months of parturition (15.25 +/- 2.8 months) than in those mated after
      that time (24.33 +/- 6.5 months). Clinical endometritis, ovarian hydrobursitis,
      and vaginal adhesions were the common clinical findings in barren females. Thus,
      efforts to reduce the age at first mating and the interval after calving,
      increase the number of herders/camels, and control reproductive disorders could
      improve the reproductive performance and quality of camel herds in Saudi Arabia.

PMID- 29450816
TI  - Thoracoscopic Blebectomy and Pleurodesis for Primary Spontaneous Pneumothorax.

PMID- 29450812
TI  - Renin angiotensin system and its role in biomarkers and treatment in gliomas.
AB  - Gliomas are the most common primary intrinsic tumor in the brain and are
      classified as low- or high-grade according to the World Health Organization
      (WHO). Patients with high-grade gliomas (HGG) who undergo surgical resection with
      adjuvant therapy have a mean overall survival of 15 months and 100% recurrence.
      The renin-angiotensin system (RAS), the primary regulator of cardiovascular
      circulation, exhibits local action and works as a paracrine system. In the
      context of this local regulation, the expression of RAS peptides and receptors
      has been detected in different kinds of tumors, including gliomas. The
      dysregulation of RAS components plays a significant role in the proliferation,
      angiogenesis, and invasion of these tumors, and therefore in their outcomes. The
      study and potential application of RAS peptides and receptors as biomarkers in
      gliomas could bring advantages against the limitations of current tumoral markers
      and should be considered in the future. The targeting of RAS components by RAS
      blockers has shown potential of being protective against cancer and improving
      immunotherapy. In gliomas, RAS blockers have shown a broad spectrum for
      beneficial effects and are being considered for use in treatment protocols. This
      review aims to summarize the background behind how RAS plays a role in
      gliomagenesis and explore the evidence that could lead to their use as biomarkers
      and treatment adjuvants.

PMID- 29450817
TI  - Prediction of Neonatal Hyperbilirubinemia Using 1st Day Serum Bilirubin Levels.
AB  - The study was conducted on Full term neonates with birth weight > 2.5 kg born in
      KIMS, Hubballi with an objective to determine the first day Total Serum Bilirubin
      (TSB) value so as to predict subsequent development of significant
      hyperbilirubinemia in term neonates. All enrolled neonates were sampled for TSB
      and blood group on Day 1 at 20 +/- 4 h and then followed up clinically by
      Kramer's rule and when the clinical jaundice by Kramer's rule was >10 mg/dl, TSB
      levels were repeated. A total of 180 newborns were enrolled for the study and 165
      babies completed the study. Out of these, 17(10.3%) babies had significant
      hyperbilirubinemia by day 5 of life. Using Receiver Operating Characteristic
      (ROC) Curve, a cut off TSB value of 6.15 mg/dl was determined with sensitivity of
      82.4%, specificity of 81.8%, positive predictive value of 32.8%, negative
      predictive value 97.6%. In term neonates, the first day total bilirubin level at
      20 +/- 4 h of life <6.15 predicts the low risk of subsequent significant
      hyperbilirubinemia with high probability.

PMID- 29450818
TI  - Congenital Hypothyroidism Due to Dyshormonogenesis in 2 Siblings.

PMID- 29450819
TI  - Familial Hypercholesterolemia: Cascade Screening in Children and Relatives of the
      Affected.
AB  - OBJECTIVE: Familial Hypercholesterolemia (FH) is an inherited disorder of lipid
      metabolism characterized by very high low density lipoprotein (LDL) cholesterol
      since birth, resulting in premature atherosclerosis and coronary artery disease
      (CAD). Cascade screening of children and family members of proven FH individuals
      can identify more subjects who have high LDL cholesterol or the family mutation
      and appropriate intervention can reduce their risk of atherosclerosis and prevent
      its complications. METHODS: Cascade screening by molecular testing, was carried
      out in 133 family members, comprising 24 children, of 31 probands with FH having
      a pathogenic mutation in LDLR/ApoB gene. Lipid profiles were obtained in 44
      family members including 11 children. RESULTS: Of 133 family members tested, 88
      (66.1%) were identified to carry the family mutation. Twelve of these were
      children below 18 y of age and 76 were adults. CAD was present in 15 (11.2%)
      family members and 63(47.4%) family members, including nine children, were
      already on Lipid Lowering Therapy. CONCLUSIONS: Cascade screening led to
      identification of 88 new cases, with a pathogenic mutation, who were at a very
      high risk of developing premature CAD. The authors identified 12 children with
      family specific mutation, out of which 9 were initiated on low dose statin
      therapy. Four homozygous children were treated with high dose statins because of
      substantially increased risk of CAD. Cascade screening, therefore, proved to be a
      successful initiative towards primary prevention of CAD in India.

PMID- 29450820
TI  - Overlapping and Distinct Cognitive Impairments in Attention-Deficit/Hyperactivity
      and Autism Spectrum Disorder without Intellectual Disability.
AB  - Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder
      (ASD) are commonly comorbid, share genetic liability, and often exhibit
      overlapping cognitive impairments. Clarification of shared and distinct cognitive
      effects while considering comorbid symptoms across disorders has been lacking. In
      the current study, children ages 7-15 years assigned to three diagnostic
      groups:ADHD (n = 509), ASD (n = 97), and controls (n = 301) completed measures
      spanning the cognitive domains of attention/arousal, working memory, set
      shifting, inhibition, and response variability. Specific processes contributing
      to response variability were examined using a drift diffusion model, which
      separately quantified drift rate (i.e., efficiency of information processing),
      boundary separation (i.e., speed-accuracy trade-offs), and non-decision time.
      Children with ADHD and ASD were impaired on attention/arousal, processing speed,
      working memory, and response inhibition, but did not differ from controls on
      measures of delayed reward discounting, set-shifting, or interference control.
      Overall, impairments in the ASD group were not attributable to ADHD symptoms
      using either continuous symptom measures or latent categorical grouping
      approaches. Similarly, impairments in the ADHD group were not attributable to ASD
      symptoms. When specific RT parameters were considered, children with ADHD and ASD
      shared impairments in drift rate. However, children with ASD were uniquely
      characterized by a wider boundary separation. Findings suggest a combination of
      overlapping and unique patterns of cognitive impairment for children with ASD as
      compared to those with ADHD, particularly when the processes underlying reaction
      time measures are considered separately.

PMID- 29450821
TI  - Episodic Life Stress and the Development of Overgeneral Autobiographical Memory
      to Positive Cues in Youth.
AB  - Overgeneral autobiographical memory (OGM) has been established as a risk factor
      for depression in both youth and adults, but questions remain as to how OGM
      develops. Although theorists have proposed that the experience of stressful life
      events may contribute to the development of OGM, no studies have examined the
      impact of negative life events on prospective changes in OGM. The goal of the
      current study was to address this gap in the literature. Participants included
      251 mothers and their biological children (aged 8-14 years old at the initial
      assessment). Using a multi-wave prospective design with assessments every 6
      months for 2 years, we found that episodic life stress predicted prospective
      decreases in youths' autobiographical memory specificity to positive, but not
      negative, cues. This study supports theories proposing that negative life events
      may contribute to the development of OGM, but suggest that, in youth, the impact
      of life stress on OGM may be specific to positive rather than negative memories.

PMID- 29450822
TI  - A troubled marriage: When electrical and mechanical dyssynchrony don't go along.

PMID- 29450823
TI  - NMR resonance assignments of RNase P protein from Thermotoga maritima.
AB  - Ribonuclase P (RNase P) is an essential metallo-endonuclease that catalyzes 5'
      precursor-tRNA (ptRNA) processing and exists as an RNA-based enzyme in bacteria,
      archaea, and eukaryotes. In bacteria, a large catalytic RNA and a small protein
      component assemble to recognize and accurately cleave ptRNA and tRNA-like
      molecular scaffolds. Substrate recognition of ptRNA by bacterial RNase P requires
      RNA-RNA shape complementarity, intermolecular base pairing, and a dynamic protein
      ptRNA binding interface. To gain insight into the binding specificity and
      dynamics of the bacterial protein-ptRNA interface, we report the backbone and
      side chain 1H, 13C, and 15N resonance assignments of the hyperthermophilic
      Thermatoga maritima RNase P protein in solution at 318 K. Our data confirm the
      formation of a stable RNA recognition motif (RRM) with intrinsic heterogeneity at
      both the N- and C-terminus of the protein, consistent with available structural
      information. Comprehensive resonance assignments of the bacterial RNase P protein
      serve as an important first step in understanding how coupled RNA binding and
      protein-RNA conformational changes give rise to ribonucleoprotein function.

PMID- 29450824
TI  - Solid-state [13C-15N] NMR resonance assignment of hepatitis B virus core protein.
AB  - Each year, nearly 900,000 deaths are due to serious liver diseases caused by
      chronic hepatitis B virus infection. The viral particle is composed of an outer
      envelope and an inner icosahedral nucleocapsid formed by multiple dimers of a ~
      20 kDa self-assembling core protein (Cp). Here we report the solid-state 13C and
      15N resonance assignments of the assembly domain, Cp149, of the core protein in
      its capsid form. A secondary chemical shift analysis of the 140 visible residues
      suggests an overall alpha-helical three-dimensional fold matching that derived
      for Cp149 from the X-ray crystallography of the capsid, and from solution-state
      NMR of the Cp149 dimer. Interestingly, however, at three distinct regions the
      chemical shifts in solution differ significantly between core proteins in the
      capsid state versus in the dimer state, strongly suggesting the respective
      residues to be involved in capsid assembly.

PMID- 29450825
TI  - Unplanned Robotic-Assisted Conversion-to-Open Colorectal Surgery is Associated
      with Adverse Outcomes.
AB  - BACKGROUND: Laparoscopic conversion-to-open colorectal surgery is associated with
      worse outcomes when compared to operations completed without conversion.
      Consequences of robotic conversion have not yet been determined. The purpose of
      this study is to compare short-term outcomes of converted robotic colorectal
      cases with those that are completed without conversion, as well as with cases
      done by the open approach. METHODS: The ACS-NSQIP database was queried for
      patients who underwent robotic completed, robotic converted-to-open, and open
      colorectal resection between 2012 and 2015. Propensity scores were estimated
      using gradient-boosted machines and converted to weights. Generalized linear
      models were fit using propensity score-weighted data. RESULTS: A total of 25,253
      patients met inclusion criteria-21,356 (84.5%) open, 3663 (14.5%) robotic
      completed, and 234 (0.9%) conversions. Conversion rate was 6.0%. Converted cases
      had significantly higher 30-day mortality rate, higher complication rate, and
      longer hospital length of stay than completed cases. Converted patients also had
      significantly higher rates of the following complications: surgical site
      infections, cardiac complications, deep venous thrombosis, postoperative ileus,
      postoperative re-intubation, renal failure, and 30-day reoperation. Compared to
      the open approach, converted patients had significantly more cardiac
      complications, postoperative reintubation, and longer operating times with no
      significant difference in 30-day mortality. CONCLUSIONS: Unplanned robotic
      conversion-to-open is associated with worse outcomes than completed cases and
      outcomes that more closely resemble traditional open colorectal surgery. Patients
      should be counseled with regard to minimally invasive conversion rates and
      outcomes. The continued pursuit of technological advancements that decrease the
      risk for conversion in minimally invasive colorectal surgery is clearly
      warranted.

PMID- 29450826
TI  - Return to Throwing after Shoulder or Elbow Injury.
AB  - PURPOSE OF REVIEW: Throwing places high demands on the human body, and specific
      characteristics are developed over time unique to these athletes. When returning
      to throw after injury, it is important to follow a criterion-based progression
      that allows the body to be prepared appropriately for the stresses that throwing
      will require. There is currently a void in the literature for criteria-based
      progression that helps these athletes return to the highest level of play. RECENT
      FINDINGS: As injury rates continue to rise in baseball, there is increased
      evidence showing contributions of the core and lower extremity to the baseball
      pitch. There is also additional data showing pitcher specific characteristics
      such as range of motion and scapular position in this unique population. The
      rehab professional should take into account every phase of the pitch starting
      from balance through ball release when designing a comprehensive return-to
      throwing program. Returning an athlete back to a throwing sport can be an
      overwhelming task. The rehabilitation specialist must have a sound understanding
      of the throwing motion as well as any biomechanical implications on the body,
      contributions throughout the kinetic chain, range of motion, and strength
      characteristics specific to the thrower as well as proper tissue loading
      principles. It is important that these athletes are not progressed too quickly
      through their programs and that a criteria-based progression is followed. They
      should have normalized range of motion, strength, and scapular mechanics,
      followed by a sound plyometric progression. Once this is achieved, they are
      advanced to an interval throwing program with increasing distance, effort, and
      volume which should be tracked for workload, making sure they do not throw more
      than their body is prepared for.

PMID- 29450827
TI  - Progression-free survival results in postmenopausal Asian women: subgroup
      analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1
      mg for hormone receptor-positive advanced breast cancer (FALCON).
AB  - BACKGROUND: The international, phase III FALCON study (NCT01602380) in
      postmenopausal patients with hormone receptor-positive, locally
      advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine
      therapy, demonstrated statistically significant improvement in progression-free
      survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg.
      This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or
      Taiwan) and non-Asian patients from the FALCON study. METHODS: Eligible patients
      (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health
      Organization performance status 0-2; >= 1 measurable/non-measurable lesion[s])
      were randomized. PFS was assessed via Response Evaluation Criteria in Solid
      Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any
      cause). Secondary endpoints included: objective response rate, clinical benefit
      rate, duration of response, and duration of clinical benefit. Consistency of
      effect across subgroups was assessed via hazard ratios and 95% confidence
      intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated.
      RESULTS: Of the 462 randomized patients, the Asian and non-Asian subgroups
      comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS
      was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard
      ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and
      13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary
      outcomes were numerically improved with fulvestrant vs anastrozole in both
      subgroups. AE profiles were generally consistent between Asian and non-Asian
      subgroups. CONCLUSIONS: Results of this subgroup analysis suggest that treatment
      effects in the Asian patient subgroup are broadly consistent with the non-Asian
      population.

PMID- 29450828
TI  - The Role of Excipients in the Stability of Triamcinolone Acetonide in Ointments.
AB  - Degradation of triamcinolone acetonide (TCA) in an ointment was investigated. TCA
      appeared to be concentrated in propylene glycol (PG) which in turn is dispersed
      in a lanolin-petrolatum mixture. Two predominant degradation products were
      identified: a 21-aldehyde and a 17-carboxylic acid. The 21-aldehyde is formed
      after TCA is oxidized by O2, a reaction that is catalyzed by trace metals.
      Logically, the content of trace metals has a profound effect on the degradation
      rate. It was shown that trace metals are extracted from lanolin and petrolatum by
      PG, increasing the concentration in PG. In accordance with these findings, TCA
      degrades faster in PG that is present in the ointment formulation than in regular
      PG. The 21-aldehyde was confirmed to be a primary degradation product, while the
      17-carboxylic acid was identified as a secondary degradation product. Based on
      the mechanism of degradation, the ointment can be stabilized by the addition of
      sodium metabisulfite which was shown to reside also in the PG phase within the
      ointment.

PMID- 29450829
TI  - Artificial Lipid Membrane Permeability Method for Predicting Intestinal Drug
      Transport: Probing the Determining Step in the Oral Absorption of Sulfadiazine;
      Influence of the Formation of Binary and Ternary Complexes with Cyclodextrins.
AB  - We propose an in vitro permeability assay by using a modified lipid membrane to
      predict the in vivo intestinal passive permeability of drugs. Two conditions were
      tested, one with a gradient pH (pH 5.5 donor/pH 7.4 receptor) and the other with
      an iso-pH 7.4. The predictability of the method was established by correlating
      the obtained apparent intestinal permeability coefficients (Papp) and the oral
      dose fraction absorbed in humans (fa) of 16 drugs with different absorption
      properties. The Papp values correlated well with the absorption rates under the
      two conditions, and the method showed high predictability and good
      reproducibility. On the other hand, with this method, we successfully predicted
      the transport characteristics of oral sulfadiazine (SDZ). Also, the tradeoff
      between the increase in the solubility of SDZ by its complex formation with
      cyclodextrins and/or aminoacids and its oral permeability was assessed. Results
      suggest that SDZ is transported through the gastrointestinal epithelium by
      passive diffusion in a pH-dependent manner. These results support the
      classification of SDZ as a high/low borderline permeability compound and are in
      agreement with the Biopharmaceutics Classification Systems (BCS). This conclusion
      is consistent with the in vivo pharmacokinetic properties of SDZ.

PMID- 29450830
TI  - Personalized Medicine and Pay for Performance: Should Pharmaceutical Firms be
      Fully Penalized when Treatment Fails?
AB  - In this article, we model the behavior of a pharmaceutical firm that has
      marketing authorization for a new therapy believed to be a candidate for
      personalized use in a subset of patients, but that lacks information as to why a
      response is seen only in some patients. We characterize the optimal outcome-based
      reimbursement policy a health authority should follow to encourage the
      pharmaceutical firm to undertake research and development activities to generate
      the information needed to effectively stratify patients. Consistent with the
      literature, we find that for a pharmaceutical firm that does not undertake
      research and development activities, when the treatment fails, the total price of
      the drug must be returned to the healthcare system (full penalization). By
      contrast, if the firm undertakes research and development activities that make
      the implementation of personalized medicine possible, treatment failure should
      not be fully penalized. Surprisingly, in some cases, particularly for high
      efficacy drugs and small target populations, the optimal policy may not require
      any penalty for treatment failure. To illustrate the main results of the
      analysis, we provide a numerical simulation and a graphical analysis.

PMID- 29450832
TI  - Perceptual Modification of the Built Environment to Influence Behavior Associated
      with Physical Activity: Quasi-Experimental Field Studies of a Stair Banister
      Illusion.
AB  - BACKGROUND: Re-engineering the built environment to influence behaviors
      associated with physical activity potentially provides an opportunity to promote
      healthier lifestyles at a population level. Here we present evidence from two
      quasi-experimental field studies in which we tested a novel, yet deceptively
      simple, intervention designed to alter perception of, and walking behavior
      associated with, stairs in an urban area. OBJECTIVES: Our objectives were to
      examine whether adjusting a stair banister has an influence on perceptions of
      stair steepness or on walking behavior when approaching the stairs. METHODS: In
      study 1, we asked participants (n = 143) to visually estimate the steepness of a
      set of stairs viewed from the top, when the stair banister was adjusted so that
      it converged with or diverged from the stairs (+/- 1.91 degrees ) or remained
      neutral (+/- 0 degrees ). In study 2, the walking behavior of participants (n =
      36) was filmed as they approached the stairs to descend, unaware of whether the
      banister converged, diverged, or was neutral. RESULTS: In study 1, participants
      estimated the stairs to be steeper if the banister diverged from, rather than
      converged with, the stairs. The effect was greater when participants were unaware
      of the adjustment. In study 2, walking speed was significantly slower when the
      banister diverged from, rather than converged with, the stairs. CONCLUSIONS:
      These findings encourage us to speculate about the potential to economically re
      engineer features of the built environment to provide opportunities for action
      (affordances) that invite physical activity behavior or even promote safer
      navigation of the environment.

PMID- 29450831
TI  - Comparison of Different Strategies for Providing Fecal Microbiota Transplantation
      to Treat Patients with Recurrent Clostridium difficile Infection in Two English
      Hospitals: A Review.
AB  - Fecal microbiota transplant (FMT) has emerged as a highly efficacious treatment
      for difficult cases of refractory and/or recurrent Clostridium difficile
      infection (CDI). There have been many well-conducted randomized controlled trials
      and thousands of patients reported in case series that describe success rates of
      approximately 90% following one or more FMT. Although the exact mechanisms of FMT
      have yet to be fully elucidated, replacement or restoration of a 'normal'
      microbiota (or at least a microbiota resembling those who have never had CDI)
      appears to have a positive effect on the gut dysbiosis that is thought to exist
      in these patients. Furthermore, despite being aesthetically unappealing, this
      'ultimate probiotic' is a particularly attractive solution to a difficult problem
      that avoids repeated courses of antibiotics. The lack of clarity about the exact
      mechanism of action and the 'active ingredient' of FMT (e.g., individual or
      communities of bacteria, bacteriophage, or bioactive molecules such as bile
      acids) has hindered the ability to produce a standardized and well-characterized
      FMT product. There is no standard method to produce material for FMT, and there
      are a multitude of factors that can vary between institutions that offer this
      therapy. Only a few studies have directly compared clinical efficacy in groups of
      patients who have been treated with FMT prepared differently (e.g., fresh vs.
      frozen) or administered by different route (e.g., by nasojejunal tube,
      colonoscopy or by oral administration of encapsulated product). More of these
      studies should be undertaken to clarify the superiority or otherwise of these
      variables. This review describes the methods and protocols that two English NHS
      hospitals independently adopted over the same time period to provide FMT for
      patients with recurrent CDI. There are several fundamental differences in the
      methods used, including selection and testing of donors, procedures for
      preparation and storage of material, and route of administration. These methods
      are described in detail in this review highlighting differing practice. Despite
      these significant methodological variations, clinical outcomes in terms of cure
      rate appear to be remarkably similar for both FMT providers. Although both
      hospitals have treated only modest numbers of patients, these findings suggest
      that many of the described differences may not be critical factors in influencing
      the success of the procedure. As FMT is increasingly being proposed for a number
      of conditions other than CDI, harmonization of methods and techniques may be more
      critical to the success of FMT, and thus it will be important to standardize
      these as far as practically possible.

PMID- 29450833
TI  - Assessing the Importance of Treatment Goals in Patients with Psoriasis: Analytic
      Hierarchy Process vs. Likert Scales.
AB  - BACKGROUND: To define treatment benefit, the Patient Benefit Index contains a
      weighting of patient-relevant treatment goals using the Patient Needs
      Questionnaire, which includes a 5-point Likert scale ranging from 0 ("not
      important at all") to 4 ("very important"). These treatment goals have been
      assigned to five health dimensions. The importance of each dimension can be
      derived by averaging the importance ratings on the Likert scales of associated
      treatment goals. OBJECTIVE: As the use of a Likert scale does not allow for a
      relative assessment of importance, the objective of this study was to estimate
      relative importance weights for health dimensions and associated treatment goals
      in patients with psoriasis by using the analytic hierarchy process and to compare
      these weights with the weights resulting from the Patient Needs Questionnaire.
      Furthermore, patients' judgments on the difficulty of the methods were
      investigated. METHODS: Dimensions of the Patient Benefit Index and their
      treatment goals were mapped into a hierarchy of criteria and sub-criteria to
      develop the analytic hierarchy process questionnaire. Adult patients with
      psoriasis starting a new anti-psoriatic therapy in the outpatient clinic of the
      Institute for Health Services Research in Dermatology and Nursing at the
      University Medical Center Hamburg (Germany) were recruited and completed both
      methods (analytic hierarchy process, Patient Needs Questionnaire). Ratings of
      treatment goals on the Likert scales (Patient Needs Questionnaire) were
      summarized within each dimension to assess the importance of the respective
      health dimension/criterion. Following the analytic hierarchy process approach,
      consistency in judgments was assessed using a standardized measurement
      (consistency ratio). RESULTS: At the analytic hierarchy process level of
      criteria, 78 of 140 patients achieved the accepted consistency. Using the
      analytic hierarchy process, the dimension "improvement of physical functioning"
      was most important, followed by "improvement of social functioning". Concerning
      the Patient Needs Questionnaire results, these dimensions were ranked in second
      and fifth position, whereas "strengthening of confidence in the therapy and in a
      possible healing" was ranked most important, which was least important in the
      analytic hierarchy process ranking. In both methods, "improvement of
      psychological well-being" and "reduction of impairments due to therapy" were
      equally ranked in positions three and four. In contrast to this, on the level of
      sub-criteria, predominantly a similar ranking of treatment goals could be
      observed between the analytic hierarchy process and the Patient Needs
      Questionnaire. From the patients' point of view, the Likert scales (Patient Needs
      Questionnaire) were easier to complete than the analytic hierarchy process
      pairwise comparisons. CONCLUSIONS: Patients with psoriasis assign different
      importance to health dimensions and associated treatment goals. In choosing a
      method to assess the importance of health dimensions and/or treatment goals, it
      needs to be considered that resulting importance weights may differ in dependence
      on the used method. However, in this study, observed discrepancies in importance
      weights of the health dimensions were most likely caused by the different
      methodological approaches focusing on treatment goals to assess the importance of
      health dimensions on the one hand (Patient Needs Questionnaire) or directly
      assessing health dimensions on the other hand (analytic hierarchy process).

PMID- 29450834
TI  - Correction to: Profiles of Social and Coping Resources in Families of Children
      with Autism Spectrum Disorder: Relations to Parent and Child Outcomes.
AB  - The original version of this article unfortunately contained a mistake.

PMID- 29450835
TI  - Correction to: Association of Autism with Maternal Infections, Perinatal and
      Other Risk Factors: A Case-Control Study.
AB  - The original version of this article unfortunately contained a mistake. The
      family name of Hadi Abou El Hassan was incorrect. The correct name is Hadi Abou
      El-Hassan.

PMID- 29450836
TI  - Allied Health Professionals' Knowledge and Use of ASD Intervention Practices.
AB  - Allied health professionals (AHPs) are trusted sources of information and
      intervention for clients with autism spectrum disorder. However, the level of
      implementation of empirically-supported therapies and the accuracy of the
      knowledge they use to inform intervention selection is largely unknown. The
      present study explored the accuracy of AHPs' knowledge and use of practices, and
      explored links to individual attitudes and organisational culture. Overall
      results from the 156 AHPs surveyed suggested general accuracy of knowledge, and
      use of empirically supported treatments, with accuracy linked to use. Use of
      practices unsupported by research was linked to organisational culture and
      openness to new interventions. The presence of misinformation and the impact on
      selection and use of effective practices are discussed.

PMID- 29450837
TI  - Associations Between the 2nd to 4th Digit Ratio and Autism Spectrum Disorder in
      Population-Based Samples of Boys and Girls: Findings from the Study to Explore
      Early Development.
AB  - The ratio of the index (2nd) finger to ring (4th) finger lengths (2D:4D) is a
      proxy for fetal testosterone and estradiol. Studies suggesting 2D:4D is inversely
      associated with autism spectrum disorder (ASD) in males were limited by lack of
      confounder and subgroup assessments. Studies of females are sparse. We examined
      associations between ASD and 2D:4D among children in the Study to Explore Early
      Development; we considered case subgroups and numerous potential demographic and
      maternal-perinatal health confounders. We observed a modest inverse association
      between ASD and right-hand 2D:4D in males; subgroup analyses indicated
      associations were limited to ASD cases with birth defects/genetic syndromes or
      dysmorphic features. We observed a positive association between ASD and left-hand
      2D:4D in females, overall and within most case subgroups.

PMID- 29450838
TI  - Prevention and Management of Obesity in Children with Autism Spectrum Disorder
      Among Primary Care Pediatricians.
AB  - Children with autism spectrum disorder (ASD) are at high risk for being
      overweight and obese. Little is known about how obesity in children with ASD is
      being addressed in primary care. This article reports findings from a survey
      completed by 327 general pediatricians, which included a fictional clinical
      vignette and Likert-scales assessing attitudes, practices, self-efficacy, and
      barriers to obesity management. Although the majority of respondents agreed
      pediatricians should be the main providers to manage obesity in children with
      ASD, few reported receiving adequate training to do so. Pediatricians were more
      likely to refer to developmental-behavioral pediatricians and dietitians for a
      child with ASD compared to a child without ASD. Higher self-efficacy was
      associated with increased weight-related counseling frequency by pediatricians.

PMID- 29450839
TI  - Characterizing Health Disparities in the Age of Autism Diagnosis in a Study of 8
      Year-Old Children.
AB  - The diagnosis of autism spectrum disorder (ASD) is often delayed from the time of
      noted concerns to the actual diagnosis. The current study used child- and family
      level factors to identify homogeneous classes in a surveillance-based sample (n =
      2303) of 8-year-old children with ASD. Using latent class analysis, a 5-class
      model emerged and the class memberships were examined in relation to the child's
      median age at ASD diagnosis. Class 3, with known language delays and a high
      advantage socioeconomically had the lowest age of ASD diagnosis (46.74 months) in
      comparison to Classes 1 (64.99 months), 4 (58.14 months), and 5 (69.78 months) in
      this sample. Findings demonstrate sociodemographic and developmental disparities
      related to the age at ASD diagnosis.

PMID- 29450840
TI  - Reply to Letter to the Editor: Giovanni Bibbo, Standardisation of shielding of
      medical X-ray installations.

PMID- 29450842
TI  - Mental Health During Residency Training: Assessing the Barriers to Seeking Care.
AB  - OBJECTIVES: Resident and fellow physicians are at elevated risk for developing
      depression compared to the general population; however, they are also less likely
      to utilize mental health services. We sought to identify the barriers to seeking
      mental health treatment among residents across all specialties at a large
      academic medical center in Chicago, IL. METHODS: Residents and fellows from all
      programs were asked to complete an anonymous self-report questionnaire. RESULTS:
      Of the 18% of residents and fellows that completed the survey, 61% felt they
      would have benefited from psychiatric services. Only 24% of those who felt they
      needed care actually sought treatment. The most commonly reported barriers to
      seeking care were lack of time (77%), concerns about confidentiality (67%),
      concerns about what others would think (58%), cost (56%), and concern for effect
      on one's ability to obtain licensure (50%). CONCLUSIONS: Despite feeling that
      they require mental health services, few trainees actually sought care. This
      study identifies an overall need for improved access to mental health providers
      and psychoeducation for medical housestaff.

PMID- 29450841
TI  - Differential Binding of Human ApoE Isoforms to Insulin Receptor is Associated
      with Aberrant Insulin Signaling in AD Brain Samples.
AB  - Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for sporadic
      Alzheimer's disease (AD), where inheritance of this isoform predisposes
      development of AD in a gene dose-dependent manner. Although the mode of action of
      ApoE4 on AD onset and progression remains unknown, we have previously shown that
      ApoE4, and not ApoE3 expression, resulted in insulin signaling deficits in the
      presence of amyloid beta (Abeta). However, these reports were not conducted with
      clinical samples that more accurately reflect human disease. In this study, we
      investigated the effect of ApoE genotype on the insulin signaling pathway in
      control and AD human brain samples. We found that targets of the insulin
      signaling pathway were attenuated in AD cases, regardless of ApoE isoform. We
      also found a decrease in GluR1 subunit expression, and an increase NR2B subunit
      expression in AD cases, regardless of ApoE isoform. Lastly, we observed that more
      insulin receptor (IR) was immunoprecipitated in control cases, and more Abeta was
      immunoprecipitated with AD cases. But, when comparing among AD cases, we found
      that more IR was immunoprecipitated with ApoE3 than ApoE4, and more Abeta was
      immunoprecipitated with ApoE4 than ApoE3. Our results suggest that the difference
      in IR binding and effect on protein expression downstream of the IR may affect
      onset and progression of AD.

PMID- 29450843
TI  - Detection of Lung Contour with Closed Principal Curve and Machine Learning.
AB  - Radiation therapy plays an essential role in the treatment of cancer. In
      radiation therapy, the ideal radiation doses are delivered to the observed tumor
      while not affecting neighboring normal tissues. In three-dimensional computed
      tomography (3D-CT) scans, the contours of tumors and organs-at-risk (OARs) are
      often manually delineated by radiologists. The task is complicated and time
      consuming, and the manually delineated results will be variable from different
      radiologists. We propose a semi-supervised contour detection algorithm, which
      firstly uses a few points of region of interest (ROI) as an approximate
      initialization. Then the data sequences are achieved by the closed polygonal line
      (CPL) algorithm, where the data sequences consist of the ordered projection
      indexes and the corresponding initial points. Finally, the smooth lung contour
      can be obtained, when the data sequences are trained by the backpropagation
      neural network model (BNNM). We use the private clinical dataset and the public
      Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI)
      dataset to measure the accuracy of the presented method, respectively. To the
      private dataset, experimental results on the initial points which are as low as
      15% of the manually delineated points show that the Dice coefficient reaches up
      to 0.95 and the global error is as low as 1.47 * 10-2. The performance of the
      proposed algorithm is also better than the cubic spline interpolation (CSI)
      algorithm. While on the public LIDC-IDRI dataset, our method achieves superior
      segmentation performance with average Dice of 0.83.

PMID- 29450844
TI  - EndoBarrier(r): a Safe and Effective Novel Treatment for Obesity and Type 2
      Diabetes?
AB  - BACKGROUND AND AIMS: Obesity associated with diabetes mellitus is a significant
      worldwide problem associated with considerable health care costs. Whilst surgical
      intervention is effective, it is invasive, costly and associated with
      complications. This study aims to evaluate the safety and efficacy of the
      EndoBarrier(r), a duodenal-jejunal sleeve bypass as an alternative treatment of
      diabetes mellitus in obese patients. MATERIALS AND METHODS: This was a multi
      centre, non-randomised trial recruiting obese patients with type 2 diabetes from
      three sites in the UK. Eligible participants had a BMI of 30-50 kg/m2 and HbA1c
      levels of 7.5-10%. The study comprised a 12-month period with the EndoBarrier(r)
      inserted and a 6-month follow-up period after it had been explanted. The primary
      study outcomes were weight, BMI, HbA1c levels and fasting insulin and glucose
      levels. RESULTS: Forty-five patients were recruited and 31 patients (69%)
      completed the 12-month study period. Significant reductions in weight (95%CI 0.62
      29.38; p < 0.05) and BMI (95%CI 1.1-8.7; p < 0.005) were documented 12 months
      after device insertion. The mean HbA1c was significantly reduced (95%CI 0.1-1.6;
      p < 0.05) after the device insertion period and reductions in metabolic
      parameters (fasting insulin and glucose levels) were also documented during the
      study. Adverse events were also assessed in all patients, the vast majority of
      which were reported as mild. CONCLUSIONS: The EndoBarrier(r) appears to be a safe
      and effective treatment strategy in overweight patients with poor glycaemic
      control despite medical therapy, or in those who are eligible but decline
      bariatric surgery.

PMID- 29450846
TI  - Regarding the Use of the Term "Cementum" in Fibro-Osseous Lesions of the
      Craniofacial Skeleton.

PMID- 29450845
TI  - Endoscopic Sleeve Gastroplasty (ESG) Is a Reproducible and Effective Endoscopic
      Bariatric Therapy Suitable for Widespread Clinical Adoption: a Large,
      International Multicenter Study.
AB  - OBJECTIVE: Endoscopic sleeve gastroplasty (ESG), an incisionless endoscopic
      bariatric procedure, has shown impressive results in case series. This study
      examines the reproducibility, efficacy, and safety in three centers across two
      countries, and identifies key determinants for procedural success. DESIGN:
      Patients who underwent ESG between February 2016 and May 2017 at one of three
      centers (Australia and USA) were retrospectively analyzed. All procedures were
      performed on an outpatient basis using the Apollo OverStitch device (Apollo
      Endosurgery, Austin, TX). Primary outcomes included absolute weight loss
      (DeltaWeight, kg), change in body mass index (?BMI, in kg/m2), total body weight
      loss (TBWL, %), excess weight loss (EWL, in %), and immediate and delayed adverse
      events. RESULTS: In total, 112 consecutive patients (male 31%, age 45.1 +/- 11.7
      years, baseline BMI 37.9 +/- 6.7 kg/m2) underwent ESG. At 1, 3, and 6 months,
      Deltaweight was 9.0 +/- 4.6 kg (TBWL 8.4 +/- 4.1%), 12.9 +/- 6.4 kg (TBWL 11.9 +/
      4.5%), and 16.4 +/- 10.7 kg (TBWL 14.9 +/- 6.1%), respectively. The proportion
      of patients who attained greater than 10% TBWL and 25% EWL was 62.2 and 78.0% at
      3 months post-ESG and 81.0 and 86.5% at 6 months post-ESG. Weight loss was
      similar between the three centers. Multivariable analysis showed that male sex,
      greater baseline body weight, and lack of prior endoscopic bariatric therapy were
      predictors of greater Deltaweight at 6 months. Three (2.7%) severe adverse events
      were observed. CONCLUSIONS: ESG is an effective, reproducible, and safe weight
      loss therapy that is suitable for widespread clinical adoption.

PMID- 29450847
TI  - Laugier-Hunziker Syndrome Presenting with Metachronous Melanoacanthomas.
AB  - Laugier-Hunziker syndrome (LHS, also termed idiopathic lenticular mucocutaneous
      hyperpigmentation) is an unusual condition characterized by progressive
      pigmentation of the mucous membranes. LHS displays a benign course and is not
      associated with malignancy. Here we present a case of LHS with a 7-year follow
      up. We document metachronous oral melanoacanthomas in this individual. In
      addition, we found that the oral melanotic macules in this patient waxed and
      waned in a cyclical manner. To our knowledge, this is the first report of these
      findings in the context of LHS. Finally, we provide an overview of other
      conditions that can present with mucosal hyperpigmentation. It is critical to
      distinguish LHS from other conditions characterized by mucosal pigmentation in
      order to facilitate optimal patient care.

PMID- 29450848
TI  - Automated Pathogenesis-Based Diagnosis of Lumbar Neural Foraminal Stenosis via
      Deep Multiscale Multitask Learning.
AB  - Pathogenesis-based diagnosis is a key step to prevent and control lumbar neural
      foraminal stenosis (LNFS). It conducts both early diagnosis and comprehensive
      assessment by drawing crucial pathological links between pathogenic factors and
      LNFS. Automated pathogenesis-based diagnosis would simultaneously localize and
      grade multiple spinal organs (neural foramina, vertebrae, intervertebral discs)
      to diagnose LNFS and discover pathogenic factors. The automated way facilitates
      planning optimal therapeutic schedules and relieving clinicians from laborious
      workloads. However, no successful work has been achieved yet due to its extreme
      challenges since 1) multiple targets: each lumbar spine has at least 17 target
      organs, 2) multiple scales: each type of target organ has structural complexity
      and various scales across subjects, and 3) multiple tasks, i.e., simultaneous
      localization and diagnosis of all lumbar organs, are extremely difficult than
      individual tasks. To address these huge challenges, we propose a deep multiscale
      multitask learning network (DMML-Net) integrating a multiscale multi-output
      learning and a multitask regression learning into a fully convolutional network.
      1) DMML-Net merges semantic representations to reinforce the salience of numerous
      target organs. 2) DMML-Net extends multiscale convolutional layers as multiple
      output layers to boost the scale-invariance for various organs. 3) DMML-Net joins
      a multitask regression module and a multitask loss module to prompt the mutual
      benefit between tasks. Extensive experimental results demonstrate that DMML-Net
      achieves high performance (0.845 mean average precision) on T1/T2-weighted MRI
      scans from 200 subjects. This endows our method an efficient tool for clinical
      LNFS diagnosis.

PMID- 29450851
TI  - ECR 2018 - BOOK OF ABSTRACTS.

PMID- 29450849
TI  - Impaired arterial responsiveness in untreated gout patients compared with healthy
      non-gout controls: association with serum urate and C-reactive protein.
AB  - To determine whether arterial responsiveness is impaired among patients with
      gout, and whether arterial responsiveness inversely correlates with serum urate
      and inflammatory measures. This is a cross-sectional study of untreated gout
      subjects (n = 34) and non-gout healthy controls (n = 64). High-resolution dynamic
      ultrasound-measured flow-mediated dilation (FMD) and nitroglycerin-mediated
      dilation (NMD) assessed endothelium-dependent and endothelium-independent
      arterial responsiveness respectively. Serum urate (sUA) and high-sensitivity C
      reactive protein (hsCRP) were measured in the gout group, and correlated with FMD
      and NMD responses. Both FMD (2.20 +/- 0.53 vs 3.56 +/- 0.31, p = 0.021) and NMD
      (16.69 +/- 1.54 vs 24.51 +/- 0.90, p = 0.00002) were impaired in the gout versus
      control group. Stratification for individual comorbidities suggested that no
      single risk factor accounted for impaired FMD/NMD in the gout subjects. However,
      the degree of association between gout and FMD, but not NMD impairment, was
      dampened after multivariable adjustment (FMD unadjusted beta = - 1.36 (SE 0.58),
      p = 0.02; adjusted beta = - 1.16 (SE 0.78), p = 0.14 and NMD unadjusted beta = -
      7.68 (SE 1.78), p < 0.0001; adjusted beta = - 5.33 (SE 2.46), p = 0.03). Within
      the gout group, there was an inverse correlation between FMD and sUA (R = - 0.5,
      p = 0.003), and between FMD and hsCRP (R = - 0.42, p = 0.017), but not between
      NMD and sUA or hsCRP. Compared with healthy controls, subjects with gout have
      reduced arterial function. Individual comorbidities are insufficient to account
      for differences between gout and control groups, but multiple comorbidities may
      collectively contribute to impairment in endothelium-dependent arterial
      responsiveness. Endothelial impairment is also related to sUA and hsCRP, markers
      of gout severity and inflammation respectively. Studies to determine whether gout
      therapy may improve arterial responsiveness are warranted.

PMID- 29450850
TI  - Recurrent fever and arthralgia as the presentation of tumor necrosis factor
      receptor-associated periodic syndrome (TRAPS) in a Chinese girl: a case report
      and review of the literature.
AB  - Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is
      characterized by recurrent episodes of inflammation with fever, abdominal pain,
      chest pain, rash, myalgia, arthralgia, conjunctivitis, and periorbital edema.
      This condition is a rare autosomal dominant disease that is strongly associated
      with heterozygous mutations in the tumor necrosis factor (TNF) receptor super
      family 1A (TNFRSF1A) gene. This condition is believed to be more common in
      Western countries than in Asian countries, and the AA amyloidosis rate for
      European countries is estimated to be 10%. Herein, we report the case of a 14
      year-old girl with recurrent fever and arthralgia with inflammatory marker
      elevation for 10 years. After extensive investigation of the infectious etiology
      with negative results and similar phenomenon observed within her family, the
      diagnosis of TRAPS was made based on next-generation sequencing, which revealed a
      T50M mutation; she was also sensitive to corticosteroids. Although none of our
      TRAPS patients developed AA amyloidosis, we suggest the continual monitoring of
      urinalysis results and serum amyloid A concentrations during long-term follow-up.
      Moreover, we also reviewed the related literature and found no Asian patients who
      had developed AA amyloidosis.

PMID- 29450852
TI  - Major pancreatic resections: normal postoperative findings and complications.
AB  - OBJECTIVES: (1) To illustrate and describe the main types of pancreatic surgery;
      (2) to discuss the normal findings after pancreatic surgery; (3) to review the
      main complications and their radiological findings. BACKGROUND: Despite the
      decreased postoperative mortality, morbidity still remains high resulting in
      longer hospitalisations and greater costs. Imaging findings following major
      pancreatic resections can be broadly divided into "normal postoperative
      alterations" and real complications. The former should regress within a few
      months whereas complications may be life-threatening and should be promptly
      identified and treated. IMAGING FINDINGS: CT is the most effective postoperative
      imaging technique. MRI and fluoroscopy are used less often and only in specific
      cases such as assessing the gastro-intestinal function or the biliary tree. The
      most common normal postoperative findings are pneumobilia, perivascular cuffing,
      fluid collections, lymphadenopathy, acute anastomotic oedema and stranding of the
      peri-pancreatic/mesenteric fat. Imaging depicts the anastomoses and the new
      postoperative anatomy. It can also demonstrate early and late complications:
      pancreatic fistula, haemorrhage, delayed gastric emptying, hepatic infarction,
      acute pancreatitis of the remnant, porto-mesenteric thrombosis, abscess, biliary
      anastomotic leaks, anastomotic stenosis and local recurrence. CONCLUSIONS:
      Radiologists should be aware of surgical procedures, postoperative anatomy and
      normal postoperative imaging findings to better detect complications and
      recurrent disease. TEACHING POINTS: * Morbidity after pancreatic resections is
      high. * CT is the most effective postoperative imaging technique. * Imaging
      depicts the anastomoses and the new postoperative anatomy. * Pancreatic fistula
      is the most common complication after partial pancreatic resection.

PMID- 29450853
TI  - Endometriosis: clinical features, MR imaging findings and pathologic correlation.
AB  - OBJECTIVE: We illustrate the magnetic resonance imaging (MRI) features of
      endometriosis. BACKGROUND: Endometriosis is a chronic gynaecological condition
      affecting women of reproductive age and may cause pelvic pain and infertility. It
      is characterized by the growth of functional ectopic endometrial glands and
      stroma outside the uterus and includes three different manifestations: ovarian
      endometriomas, peritoneal implants, deep pelvic endometriosis. The primary
      locations are in the pelvis; extrapelvic endometriosis may rarely occur.
      Diagnosis requires a combination of clinical history, invasive and non-invasive
      techniques. The definitive diagnosis is based on laparoscopy with histological
      confirmation. Diagnostic imaging is necessary for treatment planning. MRI is as a
      second-line technique after ultrasound. The MRI appearance of endometriotic
      lesions is variable and depends on the quantity and age of haemorrhage, the
      amount of endometrial cells, stroma, smooth muscle proliferation and fibrosis.
      The purpose of surgery is to achieve complete resection of all endometriotic
      lesions in the same operation. CONCLUSION: Owing to the possibility to perform a
      complete assessment of all pelvic compartments at one time, MRI represents the
      best imaging technique for preoperative staging of endometriosis, in order to
      choose the more appropriate surgical approach and to plan a multidisciplinary
      team work. TEACHING POINTS: * Endometriosis includes ovarian endometriomas,
      peritoneal implants and deep pelvic endometriosis. * MRI is a second-line imaging
      technique after US. * Deep pelvic endometriosis is associated with chronic pelvic
      pain and infertility. * Endometriosis is characterized by considerable diagnostic
      delay. * MRI is the best imaging technique for preoperative staging of
      endometriosis.

PMID- 29450855
TI  - Health-related quality of life among US military personnel injured in combat:
      findings from the Wounded Warrior Recovery Project.
AB  - PURPOSE: Little is known about the long-term, health-related quality of life
      (HRQOL) of those wounded in combat during Operations Enduring Freedom, Iraqi
      Freedom, and New Dawn. The present study described the overall HRQOL for a large
      group of US service members experiencing mild-to-severe combat-related injuries,
      and assessed the unique contribution of demographics, service- and injury-related
      characteristics, and mental health factors on long-term HRQOL. METHOD: The
      Wounded Warrior Recovery Project examines patient-reported outcomes in a cohort
      of US military personnel wounded in combat. Participants were identified from the
      Expeditionary Medical Encounter Database, a US Navy-maintained deployment health
      database, and invited to complete a web-based survey. At the time of this study,
      3245 service members consented and completed the survey. Hierarchical linear
      regression analyses were conducted to assess the unique contribution of each set
      of antecedents on HRQOL scores. RESULTS: HRQOL was uniquely associated with a
      number of demographics, and service- and injury-related characteristics.
      Nevertheless, screening positive for posttraumatic stress disorder (B = - .09; P
      < .001), depression (B = - .10; P < .001), or both as a set (B = - .19; P < .001)
      were the strongest predictors of lower long-term HRQOL. CONCLUSIONS: Postinjury
      HRQOL among service members wounded in combat was associated with service and
      injury experience, and demographic factors, but was most strongly linked with
      current mental health status. These findings underscore the significance of
      mental health issues long after injury. Further, findings reinforce that long
      term mental health screening, services, and treatment are needed for those
      injured in combat.

PMID- 29450854
TI  - Imaging of the scrotum: beyond sonography.
AB  - : The aim of this article is to describe the role of second-level imaging
      techniques after an initial ultrasonography evaluation in the assessment of
      scrotal diseases. While ultrasonography remains central as the primary imaging
      modality for the evaluation of pathologic conditions of the scrotum, the role of
      magnetic resonance imaging continues to evolve: it can actually be valuable as a
      problem-solving tool when sonographic findings are equivocal or inconclusive.
      Magnetic resonance imaging of the scrotum may provide accurate detection and
      characterization of scrotal diseases, well depicting the precise location of
      scrotal masses (intratesticular or extratesticular) and reliably characterizing
      benign conditions simulating neoplastic processes, thus preventing unnecessary
      radical surgery. Advanced magnetic resonance techniques, most of all diffusion
      weighted imaging and magnetic resonance spectroscopy, play in the meanwhile a
      more significant role in evaluating scrotal diseases. TEACHING POINTS: *
      Multiparametric ultrasonography usually represents the initial imaging modality
      for approaching scrotal diseases. * MRI is well established as a problem-solving
      tool for inconclusive sonographic findings. * Advanced MRI techniques can be
      successfully applied in scrotal pathology assessment. * MRI is valuable in
      differentiating benign conditions from neoplastic processes. * CT plays a role in
      trauma assessment and cancer staging alongside PET/CT.

PMID- 29450856
TI  - Hysterectomy and perceived physical function in middle-aged Australian women: a
      20-year population-based prospective cohort study.
AB  - PURPOSE: Hysterectomy is one of the most common gynaecological procedures
      worldwide. Changes in endocrine function may impact age-associated decline in
      physical function and these changes may be accelerated by hysterectomy. The aim
      of this study was to investigate associations between hysterectomy status and
      self-reported physical function limitations. METHODS: Our study sample (n = 8624)
      came from the mid-cohort (born 1945-1950) of the Australian Longitudinal Study on
      Women's Health (ALSWH). Self-report of physical function was measured by the
      Physical Functioning (PF) subscale of the Medical Outcomes Study Short Form
      Health Survey (SF-36) over seven surveys (1998-2016), categorised into
      substantial, moderate and minimal PF-limitations. The associations between
      hysterectomy status and de novo substantial or moderate PF-limitations versus
      minimal PF-limitations were investigated using log-multinomial regression.
      RESULTS: By Survey 8 (2016), 20% of the study sample had a hysterectomy with
      ovarian conservation (hysterectomy only) and 9% had a hysterectomy and both
      ovaries removed (hysterectomy-bilateral oophorectomy). Women with a hysterectomy
      only had a small increase in risk of substantial PF-limitations (versus minimal
      PF-limitations) compared to women with no hysterectomy (relative risk [RR]: 1.13;
      95% confidence interval [95% CI] 1.00-1.27); the point estimate was stronger for
      women with a hysterectomy-bilateral oophorectomy (RR: 1.26; 95% CI 1.09-1.46). In
      a supplementary analysis, the increased risk of substantial PF-limitations was
      seen only in women who had surgery before the age of 45 years. CONCLUSIONS:
      Compared to women with no hysterectomy, women with hysterectomy-bilateral
      oophorectomy were at increased risk of substantial PF-limitations versus minimal
      PF-limitations over 18 years of follow-up.

PMID- 29450857
TI  - Hypokalemia associated with pseudo-Cushing's syndrome and magnesium deficiency
      induced by chronic alcohol abuse.
AB  - Hypokalemia and hypomagnesemia are frequently observed in patients with chronic
      alcoholism. However, the involvement of deranged cortisol regulation in patients
      with those conditions has not been reported. A 63-year-old Japanese male with
      chronic alcoholism was referred to the Department of Diabetes, Endocrinology and
      Metabolism for examination and treatment of hypokalemic periodic paralysis.
      Laboratory findings showed hypokalemia (2.3 mmol/l), as well as a high level of
      urinary excretion of potassium and hypomagnesemia (1.2 mg/dl), whereas urinary
      excretion of magnesium was undetectable. Potassium infusion treatment recovered
      that level in serum to 4.1 mmol/l, though it decreased to 2.2 mmol/l following
      discontinuation. A dexamethasone suppression test and urinary cortisol level
      showed corticotropin-dependent hypercortisolemia. However, gadolinium-enhanced
      MRI revealed no evidence of pituitary adenoma. The patient recovered from
      hypokalemia following an administration of magnesium in addition to potassium,
      which was accompanied by potassium over-excretion improvement. After being
      discharged, serum potassium level was maintained within a normal range with only
      magnesium infusion treatment. Furthermore, alcohol intake was reduced from 160 to
      20 g/day and an endocrinological re-examination after that restriction showed
      normal cortisol regulation. The patient was diagnosed with pseudo-Cushing's
      syndrome induced by alcohol abuse. Serum potassium level was maintained within a
      normal range even after discontinuation of magnesium supplementation. Our
      findings in this case indicate that pseudo-Cushing's syndrome in conjunction with
      hypomagnesemia may be involved in development of hypokalemia in patients with
      chronic alcoholism.

PMID- 29450858
TI  - In-Source Reduction of Disulfide-Bonded Peptides Monitored by Ion Mobility Mass
      Spectrometry.
AB  - Many peptides with antimicrobial activity and/or therapeutic potential contain
      disulfide bonds as a means to enhance stability, and their quantitation is often
      performed using electrospray ionization mass spectrometry (ESI-MS). Disulfides
      can be reduced during ESI under commonly used instrument conditions, which has
      the potential to hinder accurate peptide quantitation. We demonstrate that this
      in-source reduction (ISR) is predominantly observed for peptides infused from
      acidic solutions and subjected to elevated ESI voltages (3-4 kV). ISR is readily
      apparent in the mass spectrum of oxytocin-a small, single disulfide-containing
      peptide. However, subtle m/z shifts due to partial ISR of highly charged (z >= 3)
      peptides with multiple disulfide linkages may proceed unnoticed. Ion mobility
      (IM)-MS separates ions on the basis of charge and shape in the gas phase, and
      using insulin as a model system, we show that IM-MS arrival time distributions
      (ATDs) are particularly sensitive to partial ISR of large peptides. Isotope
      modeling allows for the relative quantitation of disulfide-intact and partially
      reduced states of the mobility-separated peptide conformers. Interestingly,
      hepcidin peptides ionized from acidic solutions at elevated ESI voltages undergo
      gas-phase compaction, ostensibly due to partial disulfide ISR. Our IM-MS results
      lead us to propose that residual acid is the likely cause of disparate ATDs
      recently measured for hepcidin from different suppliers [Anal. Bioanal. Chem.
      409, 2559-2567 (2017)]. Overall, our results demonstrate the utility of IM-MS to
      detect partial ISR of disulfide-bonded peptides and reinforce the notion that
      peptide/protein measurements should be carried out using minimally activating
      instrument conditions. Graphical Abstract ?.

PMID- 29450859
TI  - Congenital Adrenal Hyperplasia (CAH) due to 21-Hydroxylase Deficiency: A
      Comprehensive Focus on 233 Pathogenic Variants of CYP21A2 Gene.
AB  - Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive
      disorders caused by complete or partial defects in one of the several
      steroidogenic enzymes involved in the synthesis of cortisol from cholesterol in
      the adrenal glands. More than 95-99% of all cases of CAH are caused by deficiency
      of steroid 21-hydroxylase, an enzyme encoded by the CYP21A2 gene. Currently,
      CYP21A2 genotyping is considered a valuable complement to biochemical
      investigations in the diagnosis of 21-hydroxylase deficiency. More than 200
      mutations have been described in literature reports, and much energy is still
      focused on the clinical classification of new variants. In this review, we focus
      on molecular genetic features of 21-hydroxylase deficiency, performing an
      extensive survey of all clinical pathogenic variants modifying the whole sequence
      of the CYP21A2 gene. Our aim is to offer a very useful tool for clinical and
      genetic specialists in order to ease clinical diagnosis and genetic counseling.

PMID- 29450861
TI  - Revision of "Aemilia" pagana Species-Group (Lepidoptera: Erebidae: Arctiinae),
      with a Description of a New Endemic Species and Comments on the Conservation
      Status.
AB  - A taxonomical rearrangement of "Aemilia" pagana species-group is proposed:
      Leucanopsis pagana (Schaus in Proc Zool Soc London 1894:225-243, 1894) comb. nov.
      and L. ninae (Orfila in Rev Soc Entomol Argent 21:67-70, 1959) comb. nov. A new
      endemic species from Pampa de Achala, Cordoba, Argentina, closer to both species,
      is described: Leucanopsis navarroi sp. nov. These three species can be recognized
      because the color pattern is the darkest among species of Leucanopsis.
      Characteristics of male genitalia suggest the nomenclatural rearrangement
      proposed. Leucanopsis pagana comb. nov. has a wide distribution from the center
      of Brazil to northeastern Argentina, including southern Paraguay. The known
      distribution and geospatial analysis suggest that this species is not in danger.
      Leucanopsis ninae comb. nov. is restricted to only one known locality (Villa
      Gesell, Buenos Aires). The restricted known distribution, the different land use
      practices, and geospatial analysis suggest that this species could be endangered.
      Leucanopsis navarroi sp. nov. is endemic to the high plateau present in the
      center of Argentina called Pampa de Achala. The known distribution and geospatial
      analysis suggest that this species could be endangered. Further studies are
      necessary to determine effectively the conservation status of these three
      species.

PMID- 29450860
TI  - Morphological Characterization of Helicoverpa armigera (Hubner) (Lepidoptera:
      Noctuidae: Heliothinae).
AB  - The cotton bollworm Helicoverpa armigera (Hubner) is a widespread lepidopteran
      pest found in various crops worldwide. This highly polyphagous species, commonly
      found both in the Old and New World, has caused significant economic damage as an
      invasive agricultural pest in Brazil since 2013. The goal of the present study is
      to provide a detailed morphological assessment of adults and immature stages of
      H. armigera, as this species is often confused with H. zea (Boddie), a congeneric
      species that is native to the New World. The biology data were acquired during
      four full life cycles, and observations on general behavior, nocturnal habits of
      larvae and adults, and sensitivity of larvae to humidity were recorded. Larval
      chaetotaxy differs between the first and the remaining instars, which bear L2 on
      the meso- and metathorax and L3 on A3 through A6, along with conspicuous chalazae
      and longitudinal bands. Important morphological characters of this species
      include the following: eggs with four micropylar openings, lined with 12 cells
      arranged in the shape of a rosette; pupa adecticous and obtect, with prominent
      spiracles; adults with the distal antennomere striate. Adults exhibit sexual
      dimorphism in the number of setae on the frenulum and spines on the prothoracic
      leg. Illustrations of the critical morphological features of this species are
      provided.

PMID- 29450862
TI  - Recent progress in dendrimer-based nanomedicine development.
AB  - Dendrimers offer well-defined nanoarchitectures with spherical shape, high degree
      of molecular uniformity, and multiple surface functionalities. Such unique
      structural properties of dendrimers have created many applications for drug and
      gene delivery, nanomedicine, diagnostics, and biomedical engineering. Dendrimers
      are not only capable of delivering drugs or diagnostic agents to desired sites by
      encapsulating or conjugating them to the periphery, but also have therapeutic
      efficacy in their own. When compared to traditional polymers for drug delivery,
      dendrimers have distinct advantages, such as high drug-loading capacity at the
      surface terminal for conjugation or interior space for encapsulation, size
      control with well-defined numbers of peripheries, and multivalency for
      conjugation to drugs, targeting moieties, molecular sensors, and biopolymers.
      This review focuses on recent applications of dendrimers for the development of
      dendrimer-based nanomedicines for cancer, inflammation, and viral infection.
      Although dendrimer-based nanomedicines still face some challenges including scale
      up production and well-characterization, several dendrimer-based drug candidates
      are expected to enter clinical development phase in the near future.

PMID- 29450863
TI  - Using Self-Reported Patient Experiences to Understand Patient Burden: Learnings
      from Digital Patient Communities in Ankylosing Spondylitis.
AB  - INTRODUCTION: Online communities contain a wealth of information containing
      unsolicited patient experiences that may go beyond what is captured by guided
      surveys or patient-reported outcome (PRO) instruments used in clinical settings.
      This study described patient experiences reported online to better understand the
      day-to-day disease burden of ankylosing spondylitis (AS). METHODS: Unguided,
      English-language patient narratives reported between January 2010 and May 2016
      were collected from 52 online sources (e.g., general/health social networking
      sites, patient-physician Q&A sites, AS forums). Using natural language processing
      combined with manual curation, patient-reported experiences within narratives
      were evaluated and categorized into social, physical, emotional, cognitive, and
      role activity (SPEC-R) concepts to assess functional impairment. The same SPEC-R
      categorization was applied to 5 AS-specific PRO instruments to evaluate their
      coverage of concepts extracted from patient narratives. RESULTS: A total of
      34,780 narratives from 3449 patients with AS were included. Physical aspects of
      AS (e.g., pain and mobility) were most commonly reported by patients (86.7%),
      followed by emotional (32.5%), cognitive (23.6%), role activity (8.7%) and social
      (5.1%). Some frequently discussed subconcepts were effectively captured by >= 2
      PRO instruments, such as pain (65.3%), asthenia (19.9%), musculoskeletal
      impairment (19.9%), depression (9.9%), and anger/frustration (5.4%); others
      [e.g., anxiety (19.1%), mental impairment (3.2%), impulsivity (2.9%)] were not
      addressed by any of the PRO instruments. CONCLUSION: These findings highlight the
      importance of analyzing patient experiences beyond clinical trial settings and
      physician reports; continuous assessment of existing PRO instruments in
      collaboration with patients may increase their utility in real-world settings.
      FUNDING: Novartis Pharmaceuticals Corporation.

PMID- 29450864
TI  - Real-World Evaluation of Direct and Indirect Economic Burden Among Endometriosis
      Patients in the United States.
AB  - INTRODUCTION: The prevalence of endometriosis and the need for treatment in the
      USA has led to the need to explore the contemporary cost burden associated with
      the disease. This retrospective cohort study compared direct and indirect
      healthcare costs in patients with endometriosis to a control group without
      endometriosis. METHODS: Women aged 18-49 years with endometriosis (date of
      initial diagnosis = index date) were identified in the Truven Health
      MarketScan(r) Commercial database between 2010 and 2014 and female control
      patients without endometriosis were matched by age and index year. The following
      outcomes were compared: healthcare resource utilization (HRU) during the 12-month
      pre- and post-index periods (including inpatient admissions, pharmacy claims,
      emergency room visits, physician office visits, and obstetrics/gynecology
      visits), annual direct (medical and pharmacy) and indirect (absenteeism, short
      term disability, and long-term disability) healthcare costs during the 12-month
      post-index period (in 2014 US$). Multivariate analyses were conducted to estimate
      annual total direct and indirect costs, controlling for demographics, pre-index
      clinical characteristics, and pre-index healthcare costs. RESULTS: Overall,
      113,506 endometriosis patients and 927,599 controls were included. Endometriosis
      patients had significantly higher HRU during both the pre- and post-index periods
      compared to controls (p < 0.0001, all categories of HRU). Approximately two
      thirds of endometriosis patients underwent an endometriosis-related surgical
      procedure (including laparotomy, laparoscopy, hysterectomy, oophorectomy, and
      other excision/ablation procedures) in the first 12 months post-index. Mean
      annual total adjusted direct costs per endometriosis patient during the 12-month
      post-index period was over three times higher than that for a non-endometriosis
      control [$16,573 (standard deviation (SD) = $21,336) vs. $4733 (SD = $14,833); p
      < 0.005]. On average, incremental direct and indirect 12-month costs per
      endometriosis patient were $10,002 and $2132 compared to their matched controls
      (p < 0.005). CONCLUSIONS: Endometriosis patients incurred significantly higher
      direct and indirect healthcare costs than non-endometriosis patients. FUNDING:
      AbbVie Inc.

PMID- 29450865
TI  - Erratum to: Super-Resolution Single Molecule FISH at the Drosophila Neuromuscular
      Junction.

PMID- 29450866
TI  - Rehabilitative orbital decompression for Graves' orbitopathy: results of a
      randomized clinical trial.
AB  - PURPOSE: Orbital decompression (OD) is a consolidated procedure for the treatment
      of exophthalmos in Graves' orbitopathy (GO). The efficacy of the various
      procedures remains unclear due to the variability of the techniques used. To
      address this issue, we performed a randomized clinical trial to compare the
      efficacy of two surgical techniques. The primary endpoint was the reduction in
      proptosis. Secondary aims were the risk of post-operative diplopia (POD) in
      primary gaze and other surgical complications. PATIENTS: 38 patients (76 orbits)
      affected with GO were enrolled and randomized into single lateral decompression
      (LD) (n = 19) or balanced medial plus lateral wall decompression (MLD) (n = 19).
      Following surgery, patients were seen for a follow-up ophthalmological evaluation
      at 6 months. Pre-operative diplopia in secondary gaze was present in 13/38
      patients (34.2%, 8/19 treated with LD and 5/19 treated with MLD). RESULTS: The
      reduction of exophthalmos was greater in patients treated with MLD (5.1 +/- 1.5
      mm, range 2-8 mm) than in those treated with LD (3.5 +/- 1.3 mm, range 1-6.5 mm)
      (p = 0.01). The overall incidence of POD in primary gaze was 5/38 (13.2%) and all
      of these patients had pre-operative diplopia in secondary gaze (5/13, 38.5%, vs
      patients with no pre-operative diplopia p = 0.005). Two of 19 patients (10.5%)
      treated with LD and 3/19 (15.8%) treated with MLD, developed POD in primary gaze,
      with no statistical difference between the two techniques. CONCLUSION: MLD
      provides a better result in terms of proptosis reduction compared to LD. The two
      techniques used here appear to have a similar safety profile in terms of POD. Pre
      operative diplopia in the secondary gaze remains a major risk factor for
      development of POD.

PMID- 29450867
TI  - 20S proteasome in the blood plasma of boys with cryptorchidism.
AB  - PURPOSE: To evaluate the concentration of 20S proteasome in the blood plasma of
      boys with cryptorchidism. METHODS: Patients-50 boys aged 1-4 years (median = 2.4
      years) with unilateral cryptorchidism. The control group-50 healthy, age-matched
      boys (aged 1-4 years, median = 2.1 years), admitted for planned herniotomy. In
      our study, we used a novel technique Surface PLASMON RESONANCE Imaging. RESULTS:
      The median concentration of 20S proteasome in the blood plasma of boys with
      cryptorchidism was 2.5-fold higher than in boys with inguinal hernia. We noticed
      statistically significant difference between 20S proteasome levels in boys with
      cryptorchidism up to 2 years old and above 2 years old. CONCLUSIONS: We believe
      that the 20S proteasome concentrations in the blood plasma of boys with
      cryptorchidism reflect the heat-induced apoptosis of germ cells.

PMID- 29450868
TI  - Hepatocholangiocarcinoma/intrahepatic cholangiocarcinoma: are they
      contraindication or indication for liver transplantation? A propensity score
      matched analysis.
AB  - BACKGROUND: Uncommon primary hepatic malignancies such as intrahepatic
      cholangiocarcinoma (ICC) and hepatocholangiocarcinoma (HCC-CC) were generally
      considered contraindications for liver transplantation(LT), and studies comparing
      the efficacy of LT and resection (LR) for ICC/HCC-CC were scarce. OBJECTIVE: To
      compare the survival outcomes of ICC/HCC-CC patients treated by LT and LR in a
      propensity score-matched population. METHOD: This is a retrospective study from
      1995 to 2015. Consecutive patients with the pathological diagnosis of ICC or HCC
      CC in the surgical specimens were included. All patients had either hepatectomy
      or LT with curative intent. Factors associated with survival were identified with
      multivariate analysis using cox-regression model. Propensity score-matched
      analysis was performed. RESULT: There were 181 patients diagnosed to have
      ICC/HCC_CC. Nine patients received LT (all with incidental ICC/HCC-CC) and 172
      received hepatectomy. The median follow-up period was 27.5 months. The median age
      was 60 years (range 3-86); Hepatitis B and C carrier status was found in 48.1 and
      2.3% of the patients, respectively. The median tumor size was 6 cm and 71.3% of
      them had solitary tumor. Microvascular invasion was present in 47% of the
      patients. After propensity score matching, there were 54 (9 in LT and 45 in LR
      group) patients for analysis. Cox-regression analysis showed that early AJCC
      (7th) staging and LT were the independent factors associated with overall
      survival. Patients in the LT group had significantly better overall survival (5
      year OS 77.8 vs 36.6%, log-rank p = 0.013). CONCLUSION: ICC/HCC-CC are uncommon
      tumors with poor long-term oncological outcomes despite curative hepatectomy.
      Liver transplantation might be a better treatment option for patients with early
      ICC/HCC-CC.

PMID- 29450870
TI  - Early and long period follow-up results of low glycemic index diet for migraine
      prophylaxis.
AB  - OBJECTIVES: The role of dietary restriction in the management of patients with
      migraine is still a controversial topic in the headache field. The aim of this
      study was to evaluate the efficacy of dietary restriction on migraine attacks.
      METHODS: Patients diagnosed with migraine without aura according to the
      International Classification of Headaches were enrolled. Our study included 350
      migraine patients evaluated at the neurology headache outpatient clinic. They
      were randomly divided into two groups: diet group as the study group and
      medication group as the control group. We told migraine patients to make
      lifestyle changes, especially those with low glycemic index in the diet group. On
      the other hand, propranolol, amitriptyline, flunarizine, and topiramate were used
      for the prophylaxis in the medication group. The frequency and severity of
      attacks [using the visual analog scale (VAS)] were recorded before starting
      dietary restriction and 1 and 3 months after the dietary restriction. RESULTS:
      There were 350 participants in this study. After 3 months, a total of 147
      patients (male/female: 17/130, mean age: 34.7+/-5.9) were evaluated in the diet
      group. The control group consisted of 147 age- and sex-matched, randomly selected
      patients with migraine without aura. In the first month after dietary
      restriction, monthly attack frequency significantly decreased in both groups but
      not the VAS score. The mean scores of VAS significantly decreased later in the
      diet group compared with those in the medication group (after 3 months).
      CONCLUSION: The results of the study revealed that low glycemic index diet intake
      can be an effective and reliable method to reduce migraine attacks.

PMID- 29450869
TI  - Long-term observation of acute-onset autoimmune hepatitis presenting clinically
      and radiologically as acute hepatitis.
AB  - BACKGROUND: There is yet no gold standard for the diagnosis of acute-onset
      autoimmune hepatitis (A-AIH), especially histologically acute AIH. As a result,
      long-term observation of A-AIH has been difficult and the nature is not well
      known. We retrospectively analyzed the clinicopathological features of A-AIH over
      a long prospective follow-up period. METHODS: Clinical, biochemical,
      immunological and pathological features of 30 patients (21 female, mean age 55.1
      +/- 13.1 years) with non-severe A-AIH "without signs of clinical and radiological
      chronicity" admitted to a community hospital between 2001 and 2015 who were
      prospectively followed for more than 2 years were analyzed retrospectively.
      RESULTS: Liver histology of 45% showed acute and 55% chronic hepatitis. Mean age
      was older, prothrombin time activity was higher, AIH scores before treatment were
      lower in histologically acute hepatitis than histologically chronic hepatitis
      significantly. Liver fibrosis was not coarse, but delicate with severe activity
      in most patients showing chronic hepatitis defined by our strict criteria. Median
      (range) follow-up period was 6.9 (2.1-16.2) years. Six (20%) patients experienced
      episode of relapses. All were alive at the last follow-up point. Corticosteroid
      was continued at 2.5-5 mg/day until the study end point without serious side
      effects in most patients. Serial change of alanine aminotransferase levels,
      immunoglobulin G levels and anti-nuclear antibody titers did not show statistical
      difference between histologically acute and chronic hepatitis. CONCLUSION: Rapid
      progression of fibrosis could occur in A-AIH. Treatment response and long-term
      prognosis were good, and not different between patients with histologically acute
      and chronic hepatitis.

PMID- 29450871
TI  - Characteristics of headache and its relationship with disease severity in
      patients with Crimean-Congo hemorrhagic fever.
AB  - OBJECTIVES: Crimean-Congo Hemorrhagic Fever (CCHF) is a fatal, tick-borne
      disease. The classic clinical presentation of CCHF is characterized by sudden
      onset of high fever, chills, and severe headache. There are no previous reports
      on the characteristics of headaches caused by CCHF. Therefore, we investigated
      the relationship between CCHF-induced headache and the clinical course of the
      disease. METHODS: We included 60 patients with headache diagnosed with CCHF; they
      were divided into two groups: group 1 included patients with hospital stay <7
      days and group 2 included patients with hospital stay >7 days. The control group
      included 43 viral pneumonia patients with headache. Patients described the
      characteristics of headaches and also self-rated the severity with a numeric pain
      scale that classified headache as either mild or severe. RESULTS: In the group
      with CCHF, 66.7% of the reported headaches met criteria for diagnosis of
      migraine. This ratio was significantly higher than that in the control group
      (37.5%). The headache severity scores in group 1 were lower than those in group
      2. The hospitalization length was shorter (p=0.004) and the platelet levels were
      higher in CCHF patients with mild headache compared with CCHF patients with
      severe headache (p=0.005). CONCLUSION: CCHF patients had more often and severe
      headaches than the controls. The severity of headache may be associated with the
      severity of vascular endothelial damage, vasodilatation, and abnormal release of
      inflammatory cytokines in CCHF similar in migraine. Most CCHF patients
      experienced migraine-like headaches, suggesting that cerebral vessel involvement
      might be important in both CCHF and migraine.

PMID- 29450872
TI  - [Turkish validity and reliability study of fear of pain questionnaire-III].
AB  - OBJECTIVES: This study aimed to develop a Turkish version of the Fear of Pain
      Questionnaire-III developed by McNeil and Rainwater (1998) and examine its
      validity and reliability indicators. METHODS: The study was conducted with 459
      university students studying in the nursing department. The Turkish translation
      of the scale was conducted by language experts and the original scale owner.
      Expert opinions were taken for language validity, and the Lawshe's content
      validity ratio formula was used to calculate the content validity. Exploratory
      factor analysis was used to assess the construct validity. The factors were
      rotated using the Varimax rotation (orthogonal) method. For reliability
      indicators of the questionnaire, the internal consistency coefficient and test re
      test reliability were utilized. RESULTS: Explanatory factor analyses using the
      three-factor model (explaining 50.5% of the total variance) revealed that the
      item factor loads varied were above the limit value of 0.30 which indicated that
      the questionnaire had good construct validity. The Cronbach's alpha value for the
      total questionnaire was 0.938, and test re-test value was 0.846 for the total
      scale. CONCLUSION: The Turkish version of the Fear of Pain Questionnaire-III had
      sufficiently high reliability and validity to be used as a tool in evaluating the
      fear of pain among the young Turkish population.

PMID- 29450873
TI  - Peripheral nerve blocks for the treatment of short-lasting unilateral
      neuralgiform headache with conjunctival injection and tearing (SUNCT) during
      pregnancy.
AB  - Short-lasting unilateral neuralgiform headache attacks with conjunctival
      injection and tearing (SUNCT) is a rare, primary headache syndrome, which is
      classified as a subtype of trigeminal autonomic cephalalgias. Although SUNCT is
      usually refractory to treatment, several antiepileptic drugs have recently shown
      promising results for its treatment. However, there is a lack of evidence
      regarding the course of SUNCT during pregnancy and the available treatment
      options. Here, we present a 30-week pregnant female with SUNCT who was
      successfully treated with infra- and supraorbital nerve blocks. Headache attacks
      completely diminished after the injection, and recurrence was not observed.
      Although lamotrigine may be relatively safe in pregnant patients with SUNCT
      attacks, peripheral nerve block may be a feasible technique and can be considered
      as a safe and effective treatment option. This is the first SUNCT case in the
      literature that was successfully treated with infra- and supraorbital nerve
      blocks during pregnancy.

PMID- 29450874
TI  - What happened? An inexplicable case: Accidental subdural block.
AB  - Epidural block is an appropriate anesthesia method for outpatient operation. This
      technique is generally safe and efficient. We present the case of a 20-year-old
      female patient with accidental subdural block after a single dose of epidural
      block for pilonidal sinus surgery. Sudden apnea, unconsciousness, and bilateral
      mydriasis occurred within a few minutes after injection. Within 80 minutes after
      injection, the patient regained full consciousness and spontaneous respiration,
      with motor block in lower extremities and sensory block until the T4 level. Motor
      block continued until 165 minutes after injection, whereas sensory block ended
      225 minutes later.

PMID- 29450875
TI  - [Coexistence of polymyalgia rheumatica with ankylosing spondylitis: A case
      report].
AB  - Ankylosing spondylitis is a chronic inflammatory disease that affects the spine
      and peripheral joints. Polymyalgia rheumatica is an inflammatory disease
      characterized by aching and prolonged morning stiffness mainly in the shoulder
      and pelvic girdles. Many other diseases may mimic polymyalgia rheumatica, and
      thus differential diagnosis is predominantly required. A wide variety of
      diseases, including spondyloarthropathies, may present polymyalgia-like symptoms,
      and two diseases rarely coexist. We present a case of a 54-year-old man who had
      been followed-up for ankylosing spondylitis and presented with pain in the
      shoulder and pelvic girdles, restricted movement, and morning stiffness for 2
      months. Physical examination revealed that the pain was located mostly in the
      shoulder and pelvic girdles. In addition, increased erythrocyte sedimentation
      rate revealed the coexistence of the two diseases. Corticosteroid treatment
      dramatically improved the patient's symptoms and supported the diagnosis. This
      case demonstrated that ankylosing spondylitis may present polymyalgia-like
      symptoms, and the two diseases may rarely coexist in the elderly. The coexistence
      of these two diseases has been rarely reported in literature. Accurate diagnosis
      of the two diseases is essential for improving the patient's symptoms and quality
      of life.

PMID- 29450876
TI  - Intravenous fentanyl as the treatment for intraoperative hiccups: A case report.

PMID- 29450877
TI  - Effect of intravenous preoperative versus postoperative paracetamol on
      postoperative nausea and vomiting in patients undergoing strabismus surgery: A
      prospective randomized study.
AB  - OBJECTIVES: This prospective randomized study aimed to compare the efficacy of
      preoperative versus postoperative paracetamol on postoperative nausea and
      vomiting (PONV) in children undergoing strabismus surgery. METHODS: Ninety-six
      patients were randomly divided into three equal groups (n=32). In the
      preoperative paracetamol group, patients received intravenous (IV) infusion of
      paracetamol [15 mg kg-1 (1.5 ml kg-1)] 1 h before surgery over 20 min and that of
      saline (1.5 ml kg-1) in the recovery room. In the postoperative paracetamol
      group, patients received IV infusion of saline (1.5 ml kg-1) 1 h before surgery
      over 20 min and that of paracetamol [15 mg kg-1 (1.5 ml kg-1)] in therecovery
      room. In the control group, patients received the IV infusion of saline (1.5 ml
      kg-1) pre- and postoperatively. Postoperative pain condition was evaluated using
      the Faces Pain Scale. In the recovery room, an observer recorded the pain score,
      complaints of nausea and vomiting, the need for rescue analgesics, and the need
      for antiemetic drug during 24 h postoperatively. RESULTS: The incidence of nausea
      and vomiting during the first 0-6 h postoperatively was significantly lower in
      the preoperative paracetamol group than in the control and postoperative
      paracetamol groups (p<0.001). The number of patients requiring antiemetic
      administration during the first 0-6 and 6-12 h postoperatively was found to be
      higher in the control group than in the other groups (p<0.001, for all).
      CONCLUSION: The preoperative administration of paracetamol reduces PONV incidence
      in children undergoing strabismus surgery.

PMID- 29450878
TI  - Antepartum risk factors for moderate to severe neonatal hypoxic ischemic
      encephalopathy: a Swedish national cohort study.
AB  - INTRODUCTION: Our aim was to identify antepartum risk factors for neonatal
      hypoxic ischemic encephalopathy, with a focus on maternal body mass index and
      height. MATERIAL AND METHODS: National population-based cohort study of 692 428
      live-born infants >=36 gestational weeks in Sweden, 2009-2015. Data from the
      Swedish Medical Birth Register and the Swedish Neonatal Quality Register were
      linked. Short maternal stature was defined as <=155 cm, and overweight as body
      mass index >=25 kg/m2 . Therapeutic hypothermia served as surrogate marker of
      moderate to severe hypoxic ischemic encephalopathy. Associations between maternal
      and infant characteristics and hypoxic ischemic encephalopathy were calculated
      with logistic regression analyses, and risks were presented as odds ratios with
      95% confidence intervals. RESULTS: Moderate to severe hypoxic ischemic
      encephalopathy occurred in 0.67/1000 infants. Nulliparity, previous cesarean
      delivery, short stature, overweight, gestational age, occiput posterior
      presentation and birthweight were all independently associated with hypoxic
      ischemic encephalopathy. The risk of hypoxic ischemic encephalopathy increased
      with decreasing maternal height and increasing body mass index. Compared with non
      short women (>=156 cm) with normal weight (body mass index <25 kg/m2 ), those
      with both short stature and overweight had increased risk of hypoxic ischemic
      encephalopathy (odds ratio 3.66; 95% confidence intervals 2.41-5.55). Among
      parous women with both short stature and overweight, the risk was almost sixfold
      (odds ratio 5.74; 95% confidence intervals 3.41-9.66). CONCLUSIONS: Antepartum
      risk factors for moderate to severe hypoxic ischemic encephalopathy included
      nulliparity, previous cesarean delivery, short stature, overweight, gestational
      age, occiput posterior presentation and birthweight. The combination of maternal
      short stature and overweight was associated with a more than threefold risk of
      subsequent hypoxic ischemic encephalopathy.

PMID- 29450879
TI  - Genetic investigation of 93 families with microphthalmia or posterior
      microphthalmos.
AB  - Microphthalmia is a developmental eye defect that is highly variable in severity
      and in its potential for systemic association. Despite the discovery of many
      disease genes in microphthalmia, at least 50% of patients remain undiagnosed
      genetically. Here, we describe a cohort of 147 patients (93 families) from our
      highly consanguineous population with various forms of microphthalmia (including
      the distinct entity of posterior microphthalmos) that were investigated using a
      next-generation sequencing multi-gene panel (i-panel) as well as whole exome
      sequencing and molecular karyotyping. A potentially causal mutation was
      identified in the majority of the cohort with microphthalmia (61%) and posterior
      microphthalmos (82%). The identified mutations (55 point mutations, 15 of which
      are novel) spanned 24 known disease genes, some of which have not or only very
      rarely been linked to microphthalmia (PAX6, SLC18A2, DSC3 and CNKSR1). Our study
      has also identified interesting candidate variants in 2 genes that have not been
      linked to human diseases (MYO10 and ZNF219), which we present here as novel
      candidates for microphthalmia. In addition to revealing novel phenotypic aspects
      of microphthalmia, this study expands its allelic and locus heterogeneity and
      highlights the need for expanded testing of patients with this condition.

PMID- 29450880
TI  - A review of cutaneous manifestations within glucagonoma syndrome: necrolytic
      migratory erythema.
AB  - Necrolytic migratory erythema (NME) is a rare skin disorder that is a cutaneous
      manifestation of the glucagonoma syndrome. It presents with annular eruptions of
      migrating erythematous papules and plaques with superficial epidermal necrosis,
      central flaccid bullae, and crusted erosions located primarily in the
      intertriginous areas. Treatment with the long-acting somatostatin analog
      Octreotide is a potential therapy to help ameliorate skin symptoms. We present a
      case of a patient with a 1-year history of a pancreatic glucagonoma that
      developed an ulcerated, plaque-like, weeping rash over multiple areas of their
      body despite current treatment with Octreotide and stable pancreatic tumor
      staging. The patient had a similar rash when initially diagnosed with a
      glucagonoma, and it quickly improved after Octreotide treatment. Clinical
      examination and biopsy were consistent with necrolytic migratory erythema due to
      an underlying glucagonoma. This rare case adds to our understanding of the
      clinical presentation of NME, as well as highlights the relapsing and remitting
      course, even if the underlying pancreatic tumor is stable and the patient is
      undergoing treatment.

PMID- 29450881
TI  - A comparative description of perceived stress and coping strategies among
      psychology and nonpsychology students in the United Arab Emirates.
AB  - PURPOSE: This study describes perceived stress and coping strategies as they
      occur within a college-aged population from an Arab background. Variables were
      compared between psychology students and their peers from other faculties. DESIGN
      AND METHODS: A cross-sectional, correlational design was used for this study. A
      total of 114 students completed the Brief COPE questionnaire, the Perceived
      Stress Scale, and a measure of our own design to assess sources of psychosocial
      support. FINDINGS: The complete sample engaged in help-seeking behavior, though
      distinct differences between groups were evident. Perceived stress was pervasive.
      Students employed a range of coping strategies but showed a clear preference for
      emotion-focused strategies. PRACTICE IMPLICATIONS: Training institutions carry
      the responsibility for developing supportive interventions to promote students'
      throughput, and ensure the graduation of competent and ethically sound
      clinicians.

PMID- 29450882
TI  - The role of neutrophils in skin damage induced by tissue-deposited lupus IgG.
AB  - Skin injury is the second most common clinical manifestation in patients with
      systemic lupus erythematosus (SLE). Neutrophils are crucial effector cells in the
      immune system but the significance of neutrophils in the pathogenesis of SLE is
      not clear. This study is to explore the role of neutrophils in the skin damage of
      SLE. We used lupus-prone mice and a C57BL/6 mouse model of lupus serum IgG
      induced skin inflammation to investigate the role of neutrophils in skin damage
      of SLE. We found that a few neutrophils infiltrated the inflammatory sites of
      skin in lupus-prone mice and the lupus-IgG-induced skin damage mouse model.
      Depletion of neutrophils did not affect the development of skin inflammation
      caused by lupus IgG, and lupus IgG can induce apoptosis of neutrophils. The
      apoptosis of neutrophils induced by lupus IgG is related to FcgammaRIII and
      Fas/Fas ligand pathways. Our study indicates that neutrophils are not major
      contributors in the skin damage caused by tissue-deposited lupus IgG but death of
      neutrophils caused by lupus IgG may provide a resource of a large amount of
      autoantigens in SLE.

PMID- 29450883
TI  - Adolescents' Friendships, Academic Achievement, and Risk Behaviors: Same-Behavior
      and Cross-Behavior Selection and Influence Processes.
AB  - This study examined to what extent adolescents' and their friends' risk behaviors
      (i.e., delinquency and alcohol use) hinder or promote their academic achievement
      (grade point average [GPA]), and vice versa. Longitudinal data were used (N =
      1,219 seventh- to ninth-grade adolescents; Mage  = 13.69). Results showed that
      risk behaviors negatively affected adolescents' GPA, whereas GPA protected
      against engaging in risk behaviors. Moreover, adolescents tended to select
      friends who have similar behaviors and friends' behaviors became more similar
      over time (same-behavior selection and influence). Furthermore, although same
      behavior effects seemed to dominate, evidence was found for some cross-behavior
      selection effects and a tendency in seventh grade for cross-behavior influence
      effects. Concluding, it is important to investigate the interplay between
      different behaviors with longitudinal social network analysis.

PMID- 29450884
TI  - Is sonographically measured cervical length at 37 weeks of gestation associated
      with intrapartum cesarean section? A prospective cohort study.
AB  - INTRODUCTION: Cesarean section rates continue to increase globally. Prediction of
      intrapartum cesarean section could lead to preventive measures. Our aim was to
      assess the association between sonographically measured cervical length at 37
      weeks of gestation and cesarean section among women planning a vaginal birth. The
      population was women with a low-risk pregnancy or with gestational diabetes.
      MATERIAL AND METHODS: This was a prospective cohort study conducted in a tertiary
      referral hospital in Sydney, Australia. In all, 212 women with a low-risk
      pregnancy or with gestational diabetes were recruited including 158 nulliparous
      and 54 parous women. Maternal demographic, clinical and ultrasound
      characteristics were collected at 37 weeks of gestation. Semi-Bayesian logistic
      regression and Markov chain Monte Carlo simulation were used to assess the
      relation between cervical length and cesarean section in labor. RESULTS: Rates of
      cesarean section were 5% (2/55) for cervical length <=20 mm, 17% (17/101) for
      cervical length 20-32 mm, and 27% (13/56) for cervical length >32 mm. These rates
      were 4, 22 and 33%, respectively, in nulliparous women. In the semi-Bayesian
      analysis, the odds ratio for cesarean section was 6.2 (95% confidence interval
      2.2-43) for cervical length 20-32 mm and 10 (95% confidence interval 4.8-74) for
      cervical length >32 mm compared with the lowest quartile of cervical length,
      after adjusting for maternal age, parity, height, prepregnancy body mass index,
      gestational diabetes, induction of labor, neonatal sex and birthweight centile.
      CONCLUSIONS: Cervical length at 37 weeks of gestation is associated with
      intrapartum cesarean section.

PMID- 29450885
TI  - Loser! On the combined impact of emotional and person-descriptive word meanings
      in communicative situations.
AB  - Humans have a unique capacity to induce intense emotional states in others by
      simple acts of verbal communication, and simple messages such as bad can elicit
      strong emotions in the addressee. However, up to now, research has mainly focused
      on general emotional meaning aspects and paradigms of low personal relevance
      (e.g., word reading), thereby possibly underestimating the impact of verbal
      emotion. In the present study, we recorded ERPs while presenting emotional words
      differing in word-inherent person descriptiveness (in that they may or may not
      refer to or describe a person; e.g., winner vs. sunflower). We predicted stronger
      emotional responses to person-descriptive words. Additionally, we enhanced the
      relevance of the words by embedding them in social-communicative contexts. We
      observed strong parallels in the characteristics of emotion and descriptiveness
      effects, suggesting a common underlying motivational basis. Furthermore, word
      inherent person descriptiveness affected emotion processing at late elaborate
      stages reflected in the late positive potential, with emotion effects found only
      for descriptive words. The present findings underline the importance of factors
      determining the personal relevance of emotional words.

PMID- 29450886
TI  - Theoretical and experimental determination of scaling factors in electron
      dosimetry for 3D-printed polylactic acid.
AB  - PURPOSE: Plastic phantoms are commonly used in daily routine for dosimetric tasks
      in radiation therapy. Although water is the reference medium according to the
      dosimetric protocols, measurements with nonwater phantoms are easier to be
      performed. To succeed absorbed dose determination, certain scaling factors have
      to be applied to the acquired measurements. Taking into account the increased
      availability of three-dimensional (3D) printing, we attempted to obtain scaling
      factors for polylactic acid (PLA), a commonly used thermoplastic material for 3D
      printing. METHODS: Measurements were performed with a custom-made phantom from
      PLA material, which was designed and constructed using 3D printing technology.
      Depth and fluence scaling factors were obtained within the range of 6 to 20 MeV.
      Moreover, Monte Carlo simulations were performed to verify the measured results.
      RESULTS: Experimental and Monte Carlo (MC) values showed a good agreement,
      especially in lower energies. Mean value of depth scaling factor (cpl ) over the
      whole range of energies was 0.946, while mean fluence scaling factor (hpl ) was
      found to be 1.050. For energies below 10 MeV, the corresponding mean values for
      cpl and hpl were 0.946 and 1.054, respectively. CONCLUSIONS: PLA phantoms could
      be constructed and used for electron beam nonreference measurements, reproducing
      even more complex geometries, from simple quality assurance devices to
      geometrically complicated anthropomorphic phantoms.

PMID- 29450887
TI  - Linear yellow papules following a cat scratch.

PMID- 29450888
TI  - Spatiotemporal heterogeneity in prey abundance and vulnerability shapes the
      foraging tactics of an omnivore.
AB  - Prey abundance and prey vulnerability vary across space and time, but we know
      little about how they mediate predator-prey interactions and predator foraging
      tactics. To evaluate the interplay between prey abundance, prey vulnerability and
      predator space use, we examined patterns of black bear (Ursus americanus)
      predation of caribou (Rangifer tarandus) neonates in Newfoundland, Canada using
      data from 317 collared individuals (9 bears, 34 adult female caribou, 274 caribou
      calves). During the caribou calving season, we predicted that landscape features
      would influence calf vulnerability to bear predation, and that bears would
      actively hunt calves by selecting areas associated with increased calf
      vulnerability. Further, we hypothesized that bears would dynamically adjust their
      foraging tactics in response to spatiotemporal changes in calf abundance and
      vulnerability (collectively, calf availability). Accordingly, we expected bears
      to actively hunt calves when they were most abundant and vulnerable, but switch
      to foraging on other resources as calf availability declined. As predicted,
      landscape heterogeneity influenced risk of mortality, and bears displayed the
      strongest selection for areas where they were most likely to kill calves, which
      suggested they were actively hunting caribou. Initially, the per-capita rate at
      which bears killed calves followed a type-I functional response, but as the
      calving season progressed and calf vulnerability declined, kill rates dissociated
      from calf abundance. In support of our hypothesis, bears adjusted their foraging
      tactics when they were less efficient at catching calves, highlighting the
      influence that predation phenology may have on predator space use. Contrary to
      our expectations, however, bears appeared to continue to hunt caribou as calf
      availability declined, but switched from a tactic of selecting areas of increased
      calf vulnerability to a tactic that maximized encounter rates with calves. Our
      results reveal that generalist predators can dynamically adjust their foraging
      tactics over short time-scales in response to changing prey abundance and
      vulnerability. Further, they demonstrate the utility of integrating temporal
      dynamics of prey availability into investigations of predator-prey interactions,
      and move towards a mechanistic understanding of the dynamic foraging tactics of a
      large omnivore.

PMID- 29450889
TI  - Olive (Olea europaea) leaf extract alters the cytokine profile of Leishmania
      major-infected macrophages: New insight into the underlying mechanism.
AB  - This study aimed to identify the effects of olive leaf extract (OLE) on IFNgamma,
      TNFalpha, TGFbeta and nitric oxide (NO) resulted from macrophages infected with
      Leishmania major (L. major) amastigotes in the culture medium. High-performance
      liquid chromatography (HPLC) was used to analyse the level of Oleuropein in plant
      extract. To evaluate the immunomodulatory effects of OLE, the isolated BALB/c
      mice peritoneal macrophages were infected with L. major promastigotes and treated
      with 6.25, 12.5 and 25 MUg/mL concentrations of OLE. To assess the cytokines,
      supernatants of cell cultures were harvested after 12, 24 and 48 hours. Cytokine
      production was evaluated by ELISA. Nitrite accumulation in the culture medium was
      assessed using the Griess reaction. The level of Oleuropein in the extract was
      18.45% by HPLC. According to results, the production of IFNgamma and TNFalpha was
      significantly increased when the infected and/or not infected macrophages with L.
      major promastigotes were affected by different concentrations of OLE. Conversely,
      the production of TGFbeta was significantly decreased under the same conditions.
      Furthermore, the colorimetric determination of NO accumulation in the culture
      medium indicated that OLE has no effect on NO production. The study corroborates
      the immunomodulatory effects of OLE on L. major-infected macrophages.

PMID- 29450890
TI  - Efficacy and safety of eslicarbazepine acetate monotherapy in patients converting
      from carbamazepine.
AB  - OBJECTIVE: To evaluate the influence of prior use of carbamazepine (CBZ) and
      other antiepileptic drugs (AEDs) with a putatively similar mechanism of action
      (inhibition of voltage-gated sodium channels; VGSCs) on seizure outcomes and
      tolerability when converting to eslicarbazepine acetate (ESL), using data pooled
      from 2 controlled conversion-to-ESL monotherapy trials (studies: 093-045, 093
      046). METHODS: Adults with treatment-resistant focal (partial-onset) seizures
      were randomized 2:1 to ESL 1600 or 1200 mg once daily. The primary efficacy
      endpoint was study exit (meeting predefined exit criteria related to worsening
      seizure control) versus an historical control group. Other endpoints included
      change in seizure frequency, responder rate, and tolerability. Endpoints were
      analyzed for subgroups of patients who received CBZ (or any VGSC inhibitor
      [VGSCi]) during baseline versus those who received other AEDs. RESULTS: Of 365
      patients in the studies, 332 were evaluable for efficacy. The higher risk of
      study exit in the subgroups that received CBZ (or any VGSCi) during baseline,
      versus other AEDs, was not statistically significant (hazard ratios were 1.49 for
      +CBZ vs -CBZ [P = .10] and 1.27 for +VGSCi vs. -VGSCi [P = .33]). Reductions in
      seizure frequency and responder rates were lower in patients who converted from
      CBZ or other VGSCi compared with those who converted from other AEDs. There were
      no notable differences in overall tolerability between subgroups, but the
      incidence of some adverse events (eg, dizziness, somnolence, nausea) differed
      between subgroups and/or between treatment periods. SIGNIFICANCE: Baseline use of
      CBZ or other major putative VGSC inhibitors did not appear to significantly
      increase the risk of study exit due to worsening seizure control, or to increase
      the frequency of side effects when converting to ESL monotherapy. However, bigger
      improvements in efficacy may be possible in patients converting to ESL
      monotherapy from an AED regimen that does not include a VGSC inhibitor.

PMID- 29450891
TI  - A public health approach for preventing neural tube defects: folic acid
      fortification and beyond.
AB  - In this paper we review the evidence basis for prevention of folic acid-sensitive
      neural tube defects (NTDs) through public health interventions in women of
      reproductive age (WRA), the proven vehicles for delivery of folic acid, and what
      is needed to effectively scale these, and provide a snapshot of potential
      innovations that require future research. Our primary focus is on the global
      situation affecting large-scale food fortification (LSFF) with folic acid, in
      particular the fortification of wheat flour and maize meal. Our overarching
      conclusion is that folic acid fortification is an evidence-based intervention
      that reduces the prevalence of NTDs, and that LSFF with folic acid is
      underutilized. Thus, food fortification with folic acid should be a component of
      most national public health strategies, in particular where folate status is
      insufficient and a fortifiable food vehicle, processed by a centralized industry,
      is consumed regularly by WRA. The evidence shows that there is still much work
      needed (1) to build the enabling environment and expand programs where there is
      currently no legislation, (2) to improve the low quality of delivery of existing
      programs, and (3) to measure and sustain programs by generating new coverage data
      and demonstrating evidence of impact in low- and middle-income countries.

PMID- 29450892
TI  - Rat choice in rapidly changing concurrent schedules.
AB  - In two experiments, experimentally naive rats were trained in concurrent variable
      interval schedules in which the reinforcer ratios changed daily according to a
      pseudorandom binary sequence. In Experiment 1, relative response rates showed
      clear sensitivity to current-session reinforcer ratios, but not to previous
      sessions' reinforcer ratios. Within sessions, sensitivity to the current
      session's reinforcement rates increased steadily, and by session end, response
      ratios approached matching to the current-session reinforcer ratios. Across
      sessions, sensitivity to the current session's reinforcer ratio decreased with
      continued exposure to the pseudorandom binary sequence, contrary to expectations
      based on previous studies demonstrating learning sets. Using a second group of
      naive rats, Experiment 2 replicated the main results from Experiment 1 and showed
      that although there were increases over sessions in both changeover rate and
      response rate during the changeover delay, neither could explain the accompanying
      reductions in sensitivity. We consider the role of reinforcement history, showing
      that our results can be simulated using two separate representations, one local
      and one nonlocal, but a more complex approach will be needed to bring together
      these results and other history effects such as learning sets and spontaneous
      recovery.

PMID- 29450893
TI  - Dofetilide for suppression of atrial fibrillation in hypertrophic cardiomyopathy:
      A case series and literature review.
AB  - BACKGROUND: Limited medical options are available for rhythm control in patients
      with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM). There are no
      published reports of dofetilide use in this population. METHODS: A retrospective
      chart review was conducted on 1,404 patients loaded on dofetilide for AF
      suppression at the Cleveland Clinic from 2008 to 2012, 25 of whom were found to
      have HCM. RESULTS: The HCM cohort was 32% female, 76% with persistent AF, mean
      age of 59 +/- 10 years, and mean ejection fraction of 54 +/- 9 %. Of the 25
      patients, 21 were discharged on dofetilide, three discontinued during loading due
      to QTc prolongation, and one due to inefficacy. There were no adverse events
      during loading. Of those discharged on dofetilide, 11/21 (52%) were still on it
      at a median follow-up of 396 (198, 699) days at the time of the chart review. For
      those in whom it was discontinued, the median time on the drug was 301 (111, 738)
      days. Of the 10 patients who discontinued dofetilide during follow-up, six were
      due to inefficacy, one postablation, one postheart transplant, one due to death
      secondary to lung cancer, and one due to worsening edema. CONCLUSIONS: Dofetilide
      was well tolerated in this group of patients with AF and HCM and it facilitated
      management of AF in 21/25 (84%) patients. Further research is needed to assess
      the safety and efficacy of dofetilide in order to develop evidence-based
      guidelines for the pharmacological management of AF in this population.

PMID- 29450894
TI  - Assessment of the correlations of lacosamide concentrations in saliva and serum
      in patients with epilepsy.
AB  - Therapeutic drug monitoring of antiepileptic drugs is based on patient serum
      samples. In this study, we evaluated the correlation between lacosamide (LCM)
      steady state concentrations in serum and saliva samples. Additionally, we
      investigated the relation with daily dose, and assessed the feasibility of saliva
      collection. This was an open-label, single center study including data from 25
      patients at the Bethel Epilepsy Center treated with LCM (50-650 mg/d). Samples
      were collected in the morning (fasting values) and in selected cases at 50
      minutes to 5 hours after the morning dose. Nonsignificant differences in the mean
      LCM morning (trough) concentration in serum and saliva were observed. Serum and
      saliva concentrations across all samples were highly correlated, (r = .874), with
      a slightly lower correlation when only fasting values were analyzed (r = .860).
      Higher correlation with daily dosages was observed in serum samples (r = .773)
      than in saliva samples (r = .604). Serum and saliva concentrations increased
      significantly after intake of the LCM morning dose (P < .001). The median
      absolute and percentage increase of LCM in serum were moderately lower than in
      saliva samples, with a few outliers in saliva samples. Consequently, saliva could
      offer great clinical potential to monitor drug concentrations and guide LCM
      treatment in epileptic patients.

PMID- 29450895
TI  - A Test of Multisession Automatic Action Tendency Retraining to Reduce Alcohol
      Consumption Among Young Adults in the Context of a Human Laboratory Paradigm.
AB  - BACKGROUND: Young adult heavy drinking is an important public health concern.
      Current interventions have efficacy but with only modest effects, and thus, novel
      interventions are needed. In prior studies, heavy drinkers, including young
      adults, have demonstrated stronger automatically triggered approach tendencies to
      alcohol-related stimuli than lighter drinkers. Automatic action tendency
      retraining has been developed to correct this tendency and consequently reduce
      alcohol consumption. This study is the first to test multiple iterations of
      automatic action tendency retraining, followed by laboratory alcohol self
      administration. METHODS: A total of 72 nontreatment-seeking, heavy drinking young
      adults ages 21 to 25 were randomized to automatic action tendency retraining or a
      control condition (i.e., "sham training"). Of these, 69 (54% male) completed 4
      iterations of retraining or the control condition over 5 days with an alcohol
      drinking session on Day 5. Self-administration was conducted according to a human
      laboratory paradigm designed to model individual differences in impaired control
      (i.e., difficulty adhering to limits on alcohol consumption). RESULTS: Automatic
      action tendency retraining was not associated with greater reduction in alcohol
      approach tendency or less alcohol self-administration than the control condition.
      The laboratory paradigm was probably sufficiently sensitive to detect an effect
      of an experimental manipulation given the range of self-administration behavior
      observed, both in terms of number of alcoholic and nonalcoholic drinks and
      measures of drinking topography. CONCLUSIONS: Automatic action tendency
      retraining was ineffective among heavy drinking young adults without motivation
      to change their drinking. Details of the retraining procedure may have
      contributed to the lack of a significant effect. Despite null primary findings,
      the impaired control laboratory paradigm is a valid laboratory-based measure of
      young adult alcohol consumption that provides the opportunity to observe drinking
      topography and self-administration of nonalcoholic beverages (i.e., protective
      behavioral strategies directly related to alcohol use).

PMID- 29450897
TI  - Molecular imprinted polymers based on magnetic chitosan with different deep
      eutectic solvent monomers for the selective separation of catechins in black tea.
AB  - Two types of molecular-imprinted polymers-based magnetic chitosan with facile
      deep eutectic solvent-functional monomers (Fe3 O4 -CTS@DES-MIPs) were synthesized
      and applied as adsorbents in magnetic solid-phase extraction (MSPE) for the
      selective recognition and separation of (+)-catechin, (-)-epicatechin, and (-)
      epigallocatechin gallate in black tea. The obtained Fe3 O4 -CTS@DES-MIPs were
      characterized by Fourier transform infrared spectroscopy and field emission
      scanning electron microscopy. The selective recognition ability was examined by
      adsorption experiments. The actual amounts of (+)-catechin, (-)-epicatechin, and
      (-)-epigallocatechin gallate extracted from black tea using Fe3 O4 -CTS@DES-MIPs
      by the MSPE method were 13.10, 6.32, and 8.76 mg/g, respectively. In addition,
      the magnetic Fe3 O4 -CTS@DES-MIPs showed outstanding recognition and selectivity.
      Therefore, it can be used to separate bioactive compounds from black tea. The new
      type of DES adopted as the functional monomer in this paper provides a new
      perspective for the recognition and separation of bioactive compounds.

PMID- 29450901
TI  - Semiempirical configuration interaction calculations for ru-centered dyes.
AB  - Computational investigation of the photochemical properties of transition-metal
      centered dyes typically involves optimization of the molecular structure followed
      by calculation of the UV/visible spectrum. At present, these steps are usually
      carried out using density functional theory (DFT) and time-dependent DFT
      calculations. Recently, we demonstrated that semiempirical methods with
      appropriate parameterization could yield geometries that were in very good
      agreement with DFT calculations, allowing large sets of molecules to be screened
      quickly and efficiently. In this article, we modify a configuration interaction
      (CI) method based on a semiempirical PM6 Hamiltonian to determine the UV/visible
      absorption spectra of Ru-centered complexes. Our modification to the CI method is
      based on a scaling of the two-center, two-electron Coulomb integrals. This
      modified, PM6-based method shows a significantly better match to the experimental
      absorption spectra versus the default configuration interaction method (in MOPAC)
      on a training set of 13 molecules. In particular, the modified PM6 method blue
      shifts the location of the metal-to-ligand charge-transfer (MLCT) peaks, in
      better agreement with experimental and DFT-based computational results,
      correcting a significant deficiency of the unmodified method. Published 2018.
      This article is a U.S. Government work and is in the public domain in the USA.

PMID- 29450896
TI  - Circadian Mechanisms in Alcohol Use Disorder and Tissue Injury.
AB  - Heavy use of alcohol can lead to addictive behaviors and to eventual alcohol
      related tissue damage. While increased consumption of alcohol has been attributed
      to various factors including level of alcohol exposure and environmental factors
      such as stress, data from behavioral scientists and physiological researchers are
      revealing roles for the circadian rhythm in mediating the development of
      behaviors associated with alcohol use disorder as well as the tissue damage that
      drives physiological disease. In this work, we compile recent work on the complex
      mutually influential relationship that exists between the core circadian rhythm
      and the pharmacodynamics of alcohol. As we do so, we highlight implications of
      the relationship between alcohol and common circadian mechanisms of effected
      organs on alcohol consumption, metabolism, toxicity, and pathology.

PMID- 29450902
TI  - Identification and expression profiles of novel odorant binding proteins and
      functional analysis of OBP99a in Bactrocera dorsalis.
AB  - Odorant-binding proteins (OBPs) in insects are essential for mating and
      oviposition host selection. How these OBPs respond to different hosts at the mRNA
      level and their effects on behavior remain poorly characterized. The oriental
      fruit fly Bactrocera dorsalis is a highly invasive agricultural pest with an
      extremely broad host range and high fecundity. Based on our previously
      constructed B. dorsalis transcriptome, six OBPs that were differentially
      expressed during three different physiological adult stages were identified. A
      phylogenetic tree was constructed to illustrate the relationships of these six
      OBPs with OBP sequences from three other dipteran species (Drosophila
      melanogaster, Anopheles gambiae, and Ceratitis capitata). The spatiotemporal
      expression profiles of the six OBPs were analyzed using quantitative real-time
      PCR. Our results revealed that OBP19c, OBP44a, OBP99a, and OBP99d were abundantly
      expressed from the prepupa stage to the adult stage, and most of the OBPs were
      mainly expressed in the head, wings, and antennae. The expression levels of these
      OBPs were upregulated when female flies were exposed to their preferred hosts.
      Silencing OBP99a resulted fewer eggs being laid compared with the control group
      when the females were exposed to their preferred host, that is, banana, whereas
      more eggs were laid when a non-preferred host, that is, tomato, was used.
      Furthermore, silencing OBP99a led to sexually dimorphic mating behavior. dsOBP99a
      injected males dramatically reduced courtship, whereas enhanced courtship was
      observed in the treated females. These data indicate that OBPs may participate in
      different biological processes of B. dorsalis. Our study will provide insight
      into the molecular mechanism of chemoreception and help develop ecologically
      friendly pest-control strategies.

PMID- 29450903
TI  - Extended physical education in children aged 6-15 years was associated with
      improved academic achievement in boys.
AB  - AIM: Physical activity (PA) has been associated with enhanced cognition, brain
      development and concentration. This study evaluated whether increased physical
      education (PE) improved academic achievement. METHODS: We recruited 304 children
      (55% boys) from a Swedish school in Skane County in 1998-2002 when they were six
      to seven years of age and followed them through all nine mandatory school years.
      Their PE level was increased from 60 to 200 minutes per week, and their results
      were compared with 73 885 control children (51% boys) in the county who graduated
      in the same years and did the standard 60 minutes of PE per week. Their academic
      achievements were measured as their final grade scores and the proportion of
      students eligible for upper secondary school. RESULTS: The eligibility for
      further education increased in the intervention boys by 6.8 percentage points and
      the mean grade score by 12.1 points, while in the control group as a whole, the
      eligibility rate decreased by 0.7 percentage points and the mean grade score
      increased by 1.7 points. No changes in eligibility rates or mean grade scores
      were seen in the intervention girls. CONCLUSION: Increasing weekly PE over nine
      years was associated with improved academic achievement in boys.

PMID- 29450904
TI  - Pt-Co nanocluster in hollow carbon nanospheres.
AB  - Recently, it has been reported that small Pt/Co bimetallic nanoclusters into
      hollow carbon spheres (HCS) show outstanding catalytic performances in deriving
      biomass fuels due to the small particle size and the homogeneous alloying. Thus,
      the knowledge about the thermal evolution and stability of the nanoclusters into
      the HCS has a great importance. We have simulated the heating process beyond the
      melting point for the bare and encapsulated Pt/Co clusters into the HCS with the
      different sizes of 55, 147, and 309. The different thermodynamic and structural
      properties of the nanoclusters have also been investigated in this work. Our
      results show that the nanoclusters are more stable into the HCS than the bare
      clusters. The melting points of the supported clusters are also higher than the
      unsupported clusters. The confined nanoclusters have also lower excess energy
      values than the bare clusters which means that the encapsulation of Pt/Co
      nanoclusters into the HCS is favorable. The structural investigations show that a
      core-shell structure cannot be observed for the different supported and
      unsupported clusters and the initial mixed structure of the different
      nanoclusters remains also at the melting points. To more investigate this claim,
      the radial chemical distribution function (RCDF) and radial distribution function
      (RDF) of the bare and encapsulated clusters have also been calculated and
      discussed. (c) 2018 Wiley Periodicals, Inc.

PMID- 29450905
TI  - A TRAMP-derived orthotopic prostate syngeneic (TOPS) cancer model for
      investigating anti-tumor treatments.
AB  - BACKGROUND: Patients with advanced prostate cancer have limited curative options,
      therefore new treatments are needed. Mouse models play a pivotal role in the
      discovery and development of new treatments. In the present study, a TRAMP
      derived Orthotopic Prostate Syngeneic (TOPS) mouse model was developed and found
      to provide a consistent means of monitoring tumor and metastatic responses to
      novel treatments. METHODS: The mouse TOPS model was generated using luciferase
      transduced TRAMP-C2 prostate cancer cells that were orthotopically injected into
      Bl6 mice by ultrasound guidance. Tumor growth and development was monitored using
      ultrasound and bioluminescence imaging. RESULTS: Tumors and metastases were
      consistently established and increases in tumor size correlated with increases in
      bioluminescence. In addition, when mice with an established tumor were castrated,
      tumor progression mirrored clinical progression. We further treated the TOPS
      model with an oncolytic Herpes Simplex virus and showed that we were able to
      monitor the therapeutic effect of the orthotopic tumor after virus treatment
      through IVIS imaging system. CONCLUSION: We have developed a powerful animal
      model to advance the current selection of effective treatments for patients with
      advanced prostate cancer.

PMID- 29450906
TI  - Factors affecting the occurrence of enteritis in 10- to 12-month-old eastern grey
      kangaroos (Macropus giganteus).
AB  - Eastern grey kangaroos (Macropus giganteus) younger than 19 months at Kanazawa
      Zoological Gardens, Japan, frequently died of enteritis. The main cause of death
      was coccidiosis. This study aimed to reveal retrospectively the clinical features
      of enteritis and factors contributing to its high occurrence. In addition,
      haematological and serum biochemical parameters in kangaroos younger than 24
      months were analyzed. The findings suggested that enteritis occurrence was higher
      in 10- to 12-month-old kangaroos than other ages and during seasons with high
      temperature and humidity than during seasons with low temperature and humidity.
      The haematological and serum biochemical analyses showed decreases in glucose,
      total cholesterol, calcium, and triglyceride levels at approximately 10 months of
      age. Joeys emerge from their mother's pouch at 8 months of age and permanently
      leave it at approximately 10 months of age. Subsequently, the joeys are exposed
      to the external environment and infectious agents. Although the joeys continue
      suckling until 13-19 months of age, the joeys start to eat the similar feed to
      the adult and their nutritional status may change at approximately 10 months of
      age. Seasonal influences, species behavior, and shifts in dietary composition are
      proposed to be contributory to the increased occurrence of enteritis between 10
      and 12 months of age.

PMID- 29450907
TI  - Molecular dynamics study of taxadiene synthase catalysis.
AB  - Molecular dynamics (MD) simulations have been performed to study the dynamic
      behavior of noncovalent enzyme carbocation complexes involved in the cyclization
      of geranylgeranyl diphosphate to taxadiene catalyzed by taxadiene synthase (TXS).
      Taxadiene and the observed four side products originate from the deprotonation of
      carbocation intermediates. The MD simulations of the TXS carbocation complexes
      provide insights into potential deprotonation mechanisms of such carbocations.
      The MD results do not support a previous hypothesis that carbocation tumbling is
      a key factor in the deprotonation of the carbocations by pyrophosphate. Instead
      water bridges are identified which may allow the formation of side products via
      multiple proton transfer reactions. A novel reaction path for taxadiene formation
      is proposed on the basis of the simulations. (c) 2018 Wiley Periodicals, Inc.

PMID- 29450908
TI  - Aquagenic pruritus successfully treated with omalizumab.

PMID- 29450909
TI  - Nature of hydration shells of a polyoxy-anion with a large cationic centre: The
      case of iodate ion in water.
AB  - The structural nature of the solvation shells of an iodate ion, which is known to
      be a polyoxy-anion with a large cationic centre, is investigated by means of Born
      Oppenheimer molecular dynamics (BOMD) simulations using BLYP and the dispersion
      corrected BLYP-D3 functionals. The iodate ion is found to have two distinct
      solvation regions around the positively charged iodine (iodine solvation shell or
      ISS) and the negatively charged oxygens (oxygen solvation shell or OSS). We have
      looked at the spatial, orientational, and hydrogen bond distributions of water in
      the two solvation regions. It is found that the water orientational profile in
      the ISS is typical of a cation hydration shell. The hydrogen bonded structure of
      water in the OSS is found to be very similar to that of the bulk water structure.
      Thus, the iodate ion essentially behaves like a positively charged iodine ion in
      water as if there is no anionic part. This explains why the cationic character of
      the iodate ion was prominently seen in earlier studies. The arrangement of water
      molecules in the two solvation shells and in the intervening regions around the
      iodate ion is further resolved by looking at structural cross-correlations. The
      electronic properties of the solvation shells are also looked at by calculating
      the solute-solvent orbital overlap and dipole moments of the solute and solvation
      shell water. We have also performed BOMD simulations of iodate ion-water clusters
      at experimentally relevant conditions. The simulation results are found to be in
      agreement with experimental results. (c) 2018 Wiley Periodicals, Inc.

PMID- 29450910
TI  - Early age exposure to moisture damage and systemic inflammation at the age of 6
      years.
AB  - Cross-sectional studies have shown that exposure to indoor moisture damage and
      mold may be associated with subclinical inflammation. Our aim was to determine
      whether early age exposure to moisture damage or mold is prospectively associated
      with subclinical systemic inflammation or with immune responsiveness in later
      childhood. Home inspections were performed in children's homes in the first year
      of life. At age 6 years, subclinical systemic inflammation was measured by serum
      C-reactive protein (CRP) and blood leukocytes and immune responsiveness by ex
      vivo production of interleukin 1-beta (IL-1beta), IL-6, and tumor necrosis factor
      alpha (TNF-alpha) in whole blood cultures without stimulation or after 24 hours
      stimulation with phorbol 12-myristate 13-acetate and ionomycin (PI),
      lipopolysaccharide (LPS), or peptidoglycan (PPG) in 251-270 children. Moisture
      damage in child's main living areas in infancy was not significantly associated
      with elevated levels of CRP or leukocytes at 6 years. In contrast, there was some
      suggestion for an effect on immune responsiveness, as moisture damage with
      visible mold was positively associated with LPS-stimulated production of TNF
      alpha and minor moisture damage was inversely associated with PI-stimulated IL
      1beta. While early life exposure to mold damage may have some influence on later
      immune responsiveness, it does not seem to increase subclinical systemic
      inflammation in later life.

PMID- 29450911
TI  - It is important not to assume an aetiology for the triad before the outcomes of
      diagnostic investigations.

PMID- 29450912
TI  - Association of clinicopathological features of melanoma with total naevus count
      and a history of dysplastic naevi: a cross-sectional retrospective study within
      an academic centre.
AB  - BACKGROUND: High naevus count (HNC) (>= 50 naevi) and presence of dysplastic
      naevi (DN) are risk factors for malignant melanoma (MM); however, MMs also occur
      in patients with low naevus count (LNC) (< 50 naevi) and in patients without DN.
      Little is known about differences between MMs in these groups. AIM: To
      characterize the clinicopathological differences between MMs in patients with HNC
      and those in patients with LNC, with or without biopsy-proven DN. METHODS: This
      was a cross-sectional retrospective chart review of 281 patients with MM seen
      between April 2013 and March 2014 at an academic pigmented lesion clinic (Boston,
      MA, USA). RESULTS: Patients with LNC MMs were diagnosed at an older age (51 vs.
      41 years, P < 0.001, OR = 0.95, 95% CI 0.93-0.97), with more aggressive MM
      features, including greater Breslow thickness (1.1 vs. 0.8 mm, P = 0.01), more
      mitoses (2 vs. 1 mitoses/mm2 , P < 0.001), lower rate of superficial spreading
      subtype (58 vs. 78%, P < 0.01, OR = 2.57, 95% CI 1.31-5.03) and higher MM stage
      (P < 0.001), compared to patients with HNC. Patients with DN had similar trends
      as those in patients with HNC described above, and in addition, were more likely
      to have a truncal MM (55 vs. 39%, P < 0.01, OR = 1.97, 95% CI 1.22-3.18) with
      less ulceration (13 vs. 29%, P < 0.01, OR = 0.36, 95% CI 0.19-0.71). Patients
      without DN were more likely to have a history of a non-MM skin cancer (32 vs.
      19%, P = 0.01, OR = 0.49, 95% CI 0.28-0.85) and an amelanotic MM (33 vs 21%, P =
      0.03, OR = 0.55, 95% CI 0.31-0.96). CONCLUSIONS: Patients with LNC may develop
      MMs with more aggressive features at an older age than patients with HNC. A
      history of biopsy-proven DN reveals distinct MM differences compared to patients
      without DN.

PMID- 29450913
TI  - In Situ Repair of 2D Chalcogenides under Electron Beam Irradiation.
AB  - Molybdenum disulfide (MoS2 ) and bismuth telluride (Bi2 Te3 ) are the two most
      common types of structures adopted by 2D chalcogenides. In view of their unique
      physical properties and structure, 2D chalcogenides have potential applications
      in various fields. However, the excellent properties of these 2D crystals depend
      critically on their crystal structures, where defects, cracks, holes, or even
      greater damage can be inevitably introduced during the preparation and
      transferring processes. Such defects adversely impact the performance of devices
      made from 2D chalcogenides and, hence, it is important to develop ways to
      intuitively and precisely repair these 2D crystals on the atomic scale, so as to
      realize high-reliability devices from these structures. Here, an in situ study of
      the repair of the nanopores in MoS2 and Bi2 Te3 is carried out under electron
      beam irradiation by transmission electron microscopy. The experimental conditions
      allow visualization of the structural dynamics of MoS2 and Bi2 Te3 crystals with
      unprecedented resolution. Real-time observation of the healing of defects at
      atomic resolution can potentially help to reproducibly fabricate and
      simultaneously image single-crystalline free-standing 2D chalcogenides. Thus,
      these findings demonstrate the viability of using an electron beam as an
      effective tool to precisely engineer materials to suit desired applications in
      the future.

PMID- 29450914
TI  - Graphene and Carbon-Nanotube Nanohybrids Covalently Functionalized by Porphyrins
      and Phthalocyanines for Optoelectronic Properties.
AB  - In recent years, there has been a rapid growth in studies of the optoelectronic
      properties of graphene, carbon nanotubes (CNTs), and their derivatives. The
      chemical functionalization of graphene and CNTs is a key requirement for the
      development of this field, but it remains a significant challenge. The focus here
      is on recent advances in constructing nanohybrids of graphene or CNTs covalently
      linked to porphyrins or phthalocyanines, as well as their application in
      nonlinear optics. Following a summary of the syntheses of nanohybrids constructed
      from graphene or CNTs and porphyrins or phthalocyanines, explicit intraconjugate
      electronic interactions between photoexcited porphyrins/phthalocyanines and
      graphene/CNTs are introduced classified by energy transfer, electron transfer,
      and charge transfer, and their optoelectronic applications are also highlighted.
      The major current challenges for the development of covalently linked nanohybrids
      of porphyrins or phthalocyanines and carbon nanostructures are also presented.

PMID- 29450915
TI  - Polymer Vesicles: Modular Platforms for Cancer Theranostics.
AB  - As an emerging field that is receiving an increasing amount of interest,
      theranostics is becoming increasingly important in the field of nanomedicine.
      Among the various smart platforms that have been proposed for use in
      theranostics, polymer vesicles (or polymersomes) are among the most promising
      candidates for integration of designated functionalities and modalities. Here, a
      brief summary of typical theranostic platforms is presented with a focus on
      modular polymer vesicles. To highlight modularity, the different methodologies
      for designing therapeutic and diagnostic modules are classified and current
      examples of theranostic vesicles that excel in both performance and design
      principle are provided. Finally, future prospects for theranostic polymer
      vesicles that can be readily prepared with functional modules are proposed.
      Overall, theranostic polymer vesicles with modular modalities and functions are
      more promising in nanomedicine than simply being "over-engineered".

PMID- 29450916
TI  - Analysis of stereoisomers of chiral drug by mass spectrometry.
AB  - Chiral molecules are of great importance in the life science since individual
      enantiomers may differ in biological activity, mechanism, and toxicity, making it
      necessary to explore efficient chiral analysis methods. Chromatography approaches
      are often used to differentiate enantiomers while mass spectrometry (MS) was
      thought to be blind in chiral analysis. With the development of MS technique, it
      began to play a more and more crucial part in chiral observation. In this review,
      we will give a detailed introduction of the analysis methods related to MS for
      chiral drugs, including its mechanism, applications, and future development.

PMID- 29450917
TI  - Factors predictive of the onset and duration of action of local anesthesia in
      mandibular third-molar surgery: a prospective study.
AB  - The aim of this study was to assess the influence of patients' and surgical
      variables on the onset and duration of action of local anesthesia (LA) in
      mandibular third-molar (M3) surgery. Patients scheduled for mandibular M3 surgery
      were considered for inclusion in this prospective cohort study. Patients' and
      surgical variables were recorded. Two per cent (2%) lidocaine with 1:100,000
      epinephrine was used to block the nerves for extraction of mandibular M3. Then,
      the onset of action and duration of LA were monitored. Univariate analysis and
      multivariate regression analysis were used to analyze the data. The final cohort
      included 88 subjects (32 men and 56 women; mean age +/- SD = 29.3 +/- 12.3 yr).
      With univariate analysis, age, gender, body mass index (BMI), smoking quantity
      and duration, operation time, and 'volume of local anesthetic needed'
      significantly influenced the onset of action and duration of LA. Multivariate
      regression revealed that age and smoking quantity were the only statistically
      significant predictors of the onset of action of LA, whereas age, smoking
      quantity, and 'volume of local anesthetic needed' were the only statistically
      significant predictors of duration of LA. Further studies are recommended to
      uncover other predictors of the onset of action and duration of LA.

PMID- 29450918
TI  - Nanoalloy Materials for Chemical Catalysis.
AB  - Nanoalloys (NAs), which are distinctly different from bulk alloys or single
      metals, take on intrinsic features including tunable components and ratios,
      variable constructions, reconfigurable electronic structures, and optimizable
      performances, which endow NAs with fascinating prospects in the catalysis field.
      Here, the focus is on NA materials for chemical catalysis (except photocatalysis
      or electrocatalysis). In terms of composition, NA systems are divided into three
      groups, noble metal, base metal, and noble/base metal mixed NAs. Their design and
      fabrication for the optimization of catalytic performance are systematically
      summarized. Additionally, the correlations between the composition/structure and
      catalytic properties are also mentioned. Lastly, the challenges faced in current
      research are discussed, and further pathways toward their development are
      suggested.

PMID- 29450919
TI  - Looking into the Future: Toward Advanced 3D Biomaterials for Stem-Cell-Based
      Regenerative Medicine.
AB  - Stem-cell-based therapies have the potential to provide novel solutions for the
      treatment of a variety of diseases, but the main obstacles to such therapies lie
      in the uncontrolled differentiation and functional engraftment of implanted
      tissues. The physicochemical microenvironment controls the self-renewal and
      differentiation of stem cells, and the key step in mimicking the stem cell
      microenvironment is to construct a more physiologically relevant 3D culture
      system. Material-based 3D assemblies of stem cells facilitate the cellular
      interactions that promote morphogenesis and tissue organization in a similar
      manner to that which occurs during embryogenesis. Both natural and artificial
      materials can be used to create 3D scaffolds, and synthetic organic and inorganic
      porous materials are the two main kinds of artificial materials. Nanotechnology
      provides new opportunities to design novel advanced materials with special
      physicochemical properties for 3D stem cell culture and transplantation. Herein,
      the advances and advantages of 3D scaffold materials, especially with respect to
      stem-cell-based therapies, are first outlined. Second, the stem cell biology in
      3D scaffold materials is reviewed. Third, the progress and basic principles of
      developing 3D scaffold materials for clinical applications in tissue engineering
      and regenerative medicine are reviewed.

PMID- 29450920
TI  - Polarization in France.
AB  - The special relationship between France and the polarization of light from the
      beginning of the 19th century until the present day is reviewed in the lives and
      works of Etienne Louis Malus, Francois Arago, Jean-Baptiste Biot, Augustin
      Fresnel, Louis Pasteur, Frederic Wallerant, Aime Cotton, Francis Perrin, and
      Alain Aspect. To avoid a redundant presentation of information that can be found
      with an Internet search engine, the author emphasizes how the aforementioned
      individuals have influenced the studies of stereochemistry, molecular chirality,
      and the polarization of light in his research group.

PMID- 29450921
TI  - Sexual Minority Adults: A National Survey on Depression, Religious
      Fundamentalism, Parent Relationship Quality & Acceptance.
AB  - Sexual minority persons from religious families may experience low acceptance by
      parents, however, little is known about the relationship of religiosity and
      parent relationships on mental health into adulthood. This study sought to test a
      moderated mediation model predicting depression based on religious
      fundamentalism, parent acceptance, and parent-child relationship quality. Sexual
      minority adult participants (n = 384) from across the U.S. completed a web-based,
      anonymous survey. Results found a conditional indirect effect of religious
      fundamentalism on depression through parent acceptance with the parent-child
      relationship quality moderating the relationship between parent acceptance and
      depression. This was significant up to age 52. Clinical implications and future
      research with sexual minority adults and their families are explored.

PMID- 29450922
TI  - Anisotropic Thermal and Guest-Induced Responses of an Ultramicroporous Framework
      with Rigid Linkers.
AB  - The interdependent effects of temperature and guest uptake on the structure of
      the ultramicroporous metal-organic framework [Cu3 (cdm)4 ] (cdm=C(CN)2 (CONH2 )-
      ) were explored in detail by using in situ neutron scattering and density
      functional theory calculations. The tetragonal lattice displays an anisotropic
      thermal response related to a hinged "lattice-fence" mechanism, unusual for this
      topology, which is facilitated by pivoting of the rigid cdm anion about the Cu
      nodes. Calculated pore-size metrics clearly illustrate the potential for
      temperature-mediated adsorption in ultramicroporous frameworks due to thermal
      fluctuations of the pore diameter near the value of the target guest kinetic
      diameter, though in [Cu3 (cdm)4 ] this is counteracted by a competing contraction
      of the pore with increasing temperature as a result of the anisotropic lattice
      response.

PMID- 29450923
TI  - Organic zinc and copper supplementation on antioxidant protective mechanism and
      their correlation with sperm functional characteristics in goats.
AB  - Trace minerals feeding had significant effects on sperm production and fertility
      with better absorption and proper utilization within the body for optimum
      reproductive function. Several studies have shown that more influenced trace
      elements in the diets of animals are copper (Cu) and zinc (Zn). Bucks showing
      deficiency of this mineral might affect the quality of semen production which in
      turn would affect the fertility. This experiment was thus designed to test the
      effects of organic Cu and Zn supplementation on antioxidants enzyme activities
      and sperm functional attributes in fresh semen of bucks. Forty bucks (n = 40,
      Aged 5 months) were assigned to ten groups of four animals in each group,
      supplemented (for a period of 8 months) with different levels of organic Zn: 20
      mg (T2), 40 mg (T3) and 60 mg (T4), organic Cu: 12.5 mg (T5), 25 mg (T6), 37.5 mg
      (T7) and combined organic Zn and Cu: 20 + 12.5 mg (T8), 40 + 25 mg (T9), 60 +
      37.5 mg (T10), respectively, per kg dry matter and no additional mineral diet
      (control; T1). One hundred and sixty semen samples were collected through electro
      ejaculator and analysed for sperm quantity, quality, acrosome intactness and
      plasma membrane integrity and correlated with the catalase, superoxide dismutase,
      glutathione peroxidase and glutathione reductase enzyme activities in seminal
      plasma. The results indicated organic Cu and zinc supplemented bucks produced
      more sperm cells, had higher sperm concentrations, maintained higher (p < .01)
      sperm livability, plasma membrane and acrosome integrities, more motility and
      velocity. The increased antioxidant enzyme activities, reduced oxidative stress
      and lowered lipid peroxidation were positively correlated (p < .05) with the
      sperm functional attributes. In conclusion, organic Cu and Zn supplement to male
      goats showed protective roles against oxidative damage and maintained better
      fresh semen characteristics.

PMID- 29450924
TI  - Electron-Catalyzed Coupling of Magnesium Amides with Aryl Iodides.
AB  - An electron was found to catalyze the coupling of magnesium diarylamides with
      aryl iodides giving triarylamines through a radical-anion intermediate. The
      transformation requires no transition metal catalysts or additives, and a wide
      array of products are formed in good-to-excellent yields.

PMID- 29450925
TI  - Enzymatic Continuous Flow Synthesis of Thiol-Terminated Poly(delta-Valerolactone)
      and Block Copolymers.
AB  - Thiol-terminated poly(delta-valerolactone) is directly synthesized via enzymatic
      6-mercapto-1-hexanol initiated ring-opening polymerization in both batch and
      microreactor. By using Candida antartica Lipase B immobilized tubular reactor,
      narrowly dispersed poly(delta-valerolactone) with higher thiol fidelity is more
      efficiently prepared in contrast to the batch reactor. Moreover, the integrated
      enzyme packed tubular reactor system is established to perform the chain
      extension experiments. Thiol-terminated poly(delta-valerolactone)-block
      poly(epsilon-caprolactone) and poly(epsilon-caprolactone)-block-poly(delta
      valerolactone) are easily prepared by modulating the monomer introduction
      sequence.

PMID- 29450926
TI  - Macroscopic Adhesion of Thermoreversible ABC Triblock Copolymer-Based Hydrogels
      Via Boronic Acid-Sugar Complexation.
AB  - Two complementary thermoreversible ABC triblock copolymers containing either
      phenylboronic acids with low pKa values or galactosyl groups in the hydrophilic B
      blocks are synthesized by sequential reversible addition-fragmentation chain
      transfer polymerization and subsequent modification of the functional groups.
      Both ABC triblock copolymers undergo reversible sol-to-gel transitions upon
      temperature change and form physically cross-linked hydrogels under physiological
      conditions. Furthermore, the spontaneous adhesion of these thermoreversible
      hydrogels via the formation of boronic esters between the phenylboronic acid and
      galactosyl groups under physiological conditions is realized for the first time.

PMID- 29450927
TI  - Histological and immunohistochemical evaluation of granulosa cells during
      different stages of folliculogenesis in bovine ovaries.
AB  - Bovine granulosa cells (GC) vary in their morphological aspect during different
      stages of folliculogenesis. In this study, 10 morphologically normal bovine
      ovaries were collected to study the structural aspects of different stages of GC
      using intermediate filament protein antibodies including cytokeratin AE1/AE3
      (AE1/AE3), vimentin, nectin-4 and desmin. Hormonal immunolocalization was
      assessed using the immunomarkers anti-Mullerian hormone (AMH) and inhibin alpha.
      In addition, tumour markers and proliferation markers using c-erbB-2 oncoprotein
      and proliferating cell nuclear antigen, respectively, were investigated. The
      immunolabelling of AE1/AE3 in GC was strongest in the early follicle stage and
      gradually decreased when reaching the Graafian follicle stage. Its
      immunolabelling increased again as the stage progressed from stage I to stage
      III. The immunolabelling of inhibin alpha was inversely proportional to that of
      AE1/AE3 in the developing ovarian follicles as their immunolabelling is opposite
      to each other during folliculogenesis. AMH was immunopositive in almost all GC
      stages in different intensities and percentages, except for some negative
      staining in the atretic IV follicles. The atretic IV follicle is a unique type of
      atretic follicle that shows Call-Exner body formation, which was mainly found in
      older cows in this study. The distinct patterns of immunoreactivity for various
      types of immunomarkers in the different GC stages will play an important role in
      diagnostic assistance of various follicle conditions, including cystic ovaries
      and GC tumours.

PMID- 29450928
TI  - Conjugated Polyelectrolytes Bearing Various Ion Densities: Spontaneous Dipole
      Generation, Poling-Induced Dipole Alignment, and Interfacial Energy Barrier
      Control for Optoelectronic Device Applications.
AB  - Conjugated polyelectrolytes (CPEs) with pi-delocalized main backbones and ionic
      pendant groups are intensively studied as interfacial layers for efficient
      polymer-based optoelectronic devices (POEDs) because they facilitate facile
      control of charge injection/extraction barriers. Here, a simple and effective
      method of performing precise interfacial energy level adjustment is presented by
      employing CPEs with different thicknesses and various ion densities under
      electric poling to realize efficient charge injection/extraction of POEDs. The
      effects of the CPE ion densities and electric (positive or negative) poling on
      the energy level tuning process are investigated by measuring the open-circuit
      voltages and current densities of devices with the structure indium tin
      oxide/zinc oxide/CPE/organic active layer/molybdenum oxide/gold while changing
      the CPE film thickness. The performances of inverted polymer light-emitting
      diodes and inverted polymer solar cells are remarkably improved by precisely
      controlling the interfacial energy level matching using optimum CPE conditions.

PMID- 29450929
TI  - Dehydration Polymerization for Poly(hetero)arene Conjugated Polymers.
AB  - The lack of scalable and sustainable methods to prepare conjugated polymers
      belies their importance in many enabling technologies. Accessing high-performance
      poly(hetero)arene conjugated polymers by dehydration has remained an unsolved
      problem in synthetic chemistry and has historically required transitional-metal
      coupling reactions. Herein, we report a dehydration method that allows access to
      conjugated heterocyclic materials. By using the technique, we have prepared a
      series of small molecules and polymers. The reaction avoids using transition
      metals, proceeds at room temperature, the only required reactant is a simple base
      and water is the sole by-product. The dehydration reaction is technically simple
      and provides a sustainable and straightforward method to prepare conjugated
      heteroarene motifs.

PMID- 29450930
TI  - Neonatal meningococcal disease.

PMID- 29450931
TI  - Sulfur Radical Transfer and Coupling Reaction to Benzoxazine Groups: A New
      Reaction Route for Preparation of Polymeric Materials Using Elemental Sulfur as a
      Feedstock.
AB  - A novel approach to preparing polymeric materials using elemental sulfur as a
      feedstock through the newly developed sulfur radical transfer and coupling (SRTC)
      reaction is reported herein. Polybenzoxazines with high sulfur contents are
      prepared using the SRTC reaction with benzoxazine compounds as the radical
      acceptors. The reactions between elemental sulfur and benzoxazine rings are
      analyzed with Fourier transform infrared (FTIR), 1 H NMR, and 13 C DEPT
      spectroscopies to elucidate the SRTC reaction mechanism. Moreover, the prepared
      polybenzoxazine-sulfur hybrid materials show attractive repairing properties
      based on the dynamic S-S linkages. An effective reaction mechanism and the
      prepared repairable sulfur-possessing polymeric materials are demonstrated.

PMID- 29450933
TI  - Face cooling reveals a relative inability to increase cardiac parasympathetic
      activation during passive heat stress.
AB  - NEW FINDINGS: What is the central question of this study? Does passive heat
      stress attenuate the increase in cardiac parasympathetic stimulation, vascular
      resistance and blood pressure evoked by face cooling? What is the main finding
      and its importance? Passive heat stress attenuates the capacity to increase
      cardiac parasympathetic activation and impairs the ability to increase vascular
      resistance during sympathoexcitation, which ultimately results in a relative
      inability to increase blood pressure. These findings cast doubt on the efficacy
      of face cooling at augmenting blood pressure during orthostasis while heat
      stressed. ABSTRACT: We tested the hypothesis that passive heat stress attenuates
      the increase in cardiac parasympathetic stimulation, vascular resistance and
      blood pressure evoked by face cooling. During normothermia and when intestinal
      temperature was elevated by 1.0 +/- 0.2 degrees C, 10 healthy young adults
      underwent 3 min of face cooling. Face cooling was accomplished by placing a 2.5
      litre bag of ice water (0 +/- 0 degrees C) over the cheeks, eyes and forehead.
      Primary variables included forehead skin temperature, mean arterial pressure and
      systemic, forearm and cutaneous vascular resistances. Indices of heart rate
      variability in the time domain provided an index of cardiac parasympathetic
      activity. The magnitude of reduction in forehead skin temperature during face
      cooling was slightly greater during normothermia (-17.6 +/- 1.9 versus -16.3 +/-
      3.0 degrees C, P = 0.03). Increases in heart rate variability evoked by face
      cooling were attenuated during heat stress. Changes in systemic, forearm and
      cutaneous vascular resistances during face cooling were virtually abolished
      during heat stress (P < 0.01). However, when forearm and vascular data were
      reported as conductance, differences between normothermia and heat stress were
      not apparent (P >= 0.62). Nevertheless, the increase in mean arterial pressure
      was attenuated during heat stress with face cooling (at 3 min: 2 +/- 7 mmHg)
      compared with normothermia (at 3 min: 19 +/- 7 mmHg, P < 0.01). These data
      indicate that passive heat stress attenuates face cooling-evoked increases in
      cardiac parasympathetic activation, vascular resistance and blood pressure.
      However, they also indicate that changes in indices of vascular resistance do not
      always reflect equivalent changes in conductance.

PMID- 29450932
TI  - Cardiorespiratory noise correction improves the ASL signal.
AB  - Cardiorespiratory fluctuations such as changes in heart rate or respiration
      volume influence the temporal dynamics of cerebral blood flow (CBF) measurements
      during arterial spin labeling (ASL) fMRI. This "physiological noise" can confound
      estimates of resting state network activity, and it may lower the signal-to-noise
      ratio of ASL during task-related experiments. In this study we examined several
      methods for minimizing the contributions of both synchronized and non
      synchronized physiological noise in ASL measures of CBF, by combining the
      RETROICOR approach with different linear deconvolution models. We evaluated the
      amount of variance in CBF that could be explained by each method during
      physiological rest, in both resting state and task performance conditions. To
      further demonstrate the feasibility of this approach, we induced low-frequency
      cardiorespiratory deviations via peripheral adrenergic stimulation with
      isoproterenol, and determined how these fluctuations influenced CBF, before and
      after applying noise correction. By suppressing physiological noise, we observed
      substantial improvements in the signal-to-noise ratio at the individual and group
      activation levels. Our results suggest that variations in cardiac and respiratory
      parameters can account for a large proportion of the variance in resting and task
      based CBF, and indicate that regressing out these non-neuronal signal variations
      improves the intrinsically low signal-to-noise ratio of ASL. This approach may
      help to better identify and control physiologically driven activations in ASL
      resting state and task-based analyses.

PMID- 29450934
TI  - Imaging Proton Transport in Giant Vesicles through Cyclic Peptide-Polymer
      Conjugate Nanotube Transmembrane Ion Channels.
AB  - Since their discovery in 1993, interest in various aspects of cyclic peptides
      (CPs) has expanded rapidly. Of particular note is their potential to form
      artificial ion channels in lipid membranes, an attractive characteristic in
      supramolecular chemistry and biological research. The design and synthesis of
      cyclic peptide-polymer conjugates (CPPCs) that can self-assemble within lipid
      bilayers into nanotubes, mimicking naturally occurring membrane channels and
      pores, has been reported. However, methods that allow direct detection of the
      transport process with high levels of certainty are still lacking. This work
      focuses on the development of a simple but reliable approach to verify and
      quantify proton transport across a bilayer membrane. Giant unilamellar vesicles
      (GUVs) are created via the electroformation method and CPPCs are incorporated in
      GUV membranes at varying concentrations (0-10%). Confocal fluorescence microscopy
      is used to demonstrate full inclusion of fluorescein-labeled CPPCs in the GUV
      membranes. The pH-sensitive dye carboxyfluorescein is encapsulated within the
      water pool of the GUVs and used as an indicator of proton transport. This assay
      is versatile and can be exploited on other existing proton transporter systems,
      providing a consistent tool to compare their performances. It should also aid the
      development of novel antineoplastics and drug delivery systems.

PMID- 29450935
TI  - Community violence exposure correlates with smaller gray matter volume and lower
      IQ in urban adolescents.
AB  - Adolescents' exposure to community violence is a significant public health issue
      in urban settings and has been associated with poorer cognitive performance and
      increased risk for psychiatric illnesses, including PTSD. However, no study to
      date has investigated the neural correlates of community violence exposure in
      adolescents. Sixty-five healthy adolescents (age = 14-18 years; 36 females, 29
      males) from moderate- to high-crime neighborhoods in Los Angeles reported their
      violence exposure, parents' education level, and free/reduced school lunch status
      (socio-economic status, SES), and underwent structural neuroimaging and
      intelligence testing. Violence exposure negatively correlated with measures of
      SES, IQ, and gray matter volume. Above and beyond the effect of SES, violence
      exposure negatively correlated with IQ and with gray matter volume in the left
      inferior frontal gyrus and anterior cingulate cortex, regions involved in high
      level cognitive functions and autonomic modulation, and previously shown to be
      reduced in PTSD and combat-exposed military populations. The current results
      provide first evidence that frontal brain regions involved in cognition and
      affect appear to be selectively affected by exposure to community violence, even
      in healthy nondelinquent adolescents who are not the direct victims or
      perpetrators of violence.

PMID- 29450936
TI  - Correcting for missing and irregular data in home-range estimation.
AB  - Home-range estimation is an important application of animal tracking data that is
      frequently complicated by autocorrelation, sampling irregularity, and small
      effective sample sizes. We introduce a novel, optimal weighting method that
      accounts for temporal sampling bias in autocorrelated tracking data. This method
      corrects for irregular and missing data, such that oversampled times are
      downweighted and undersampled times are upweighted to minimize error in the home
      range estimate. We also introduce computationally efficient algorithms that make
      this method feasible with large data sets. Generally speaking, there are three
      situations where weight optimization improves the accuracy of home-range
      estimates: with marine data, where the sampling schedule is highly irregular,
      with duty cycled data, where the sampling schedule changes during the observation
      period, and when a small number of home-range crossings are observed, making the
      beginning and end times more independent and informative than the intermediate
      times. Using both simulated data and empirical examples including reef manta ray,
      Mongolian gazelle, and African buffalo, optimal weighting is shown to reduce the
      error and increase the spatial resolution of home-range estimates. With a
      conveniently packaged and computationally efficient software implementation, this
      method broadens the array of data sets with which accurate space-use assessments
      can be made.

PMID- 29450937
TI  - Adaptation of mineral trioxide aggregate to dentine walls compared with other
      root-end filling materials: A systematic review.
AB  - This systematic review analysed the literature comparing marginal adaptation of
      mineral trioxide aggregate (MTA) with other filling materials in root-end
      cavities. The PubMed, Ovid, Web of Science, SCOPUS, and Cochrane library
      databases were searched using appropriate keywords related to root-end filling
      materials and adaptation. Of 38 articles assessed, 20 met the inclusion criteria.
      No in vivo study was identified. In 10 studies, MTA gave the best marginal
      adaptation results, but no significant differences were found between MTA and any
      of the tested filling materials in seven studies. There was great variability in
      the study designs including analysed surface, unit of gap measurement and
      magnification amount during analysis. On the basis of available evidence, MTA
      presented good marginal adaptation to dentine walls. This review identified the
      need for the development of standardised methods to evaluate the adaptation
      property of root-end filling materials in ex vivo studies as well as in clinical
      studies evaluating outcome.

PMID- 29450938
TI  - Hot Off the Press: Peripheral Intravenous Cannula Insertion and Use in the
      Emergency Department.
AB  - This is a prospective before-after study comparing peripheral intravenous
      cannulation (PIVC) placement and usage rates following a 10-week-long multimodal
      intervention provided to medical and nursing staff working in a tertiary
      emergency department (ED). The intervention focused on improving appropriate use
      of PIVCs in an emergency setting by emphasizing to clinicians that a PIVC should
      only be placed if it was believed there was more than an 80% chance that it would
      be used. Patients were eligible for the study if they presented to the ED and
      were >18 years of age. Patients were excluded from the study if they were triage
      category 1, already had a PIVC placed in an ambulance, or were transferred from
      another hospital. Among the 4,172 patients included in the analysis, there was a
      9.8% reduction in the number of PIVCs inserted (95% confidence interval [CI] =
      6.8-12.87) and a 12% increase in PIVC usage (95% CI = 8.7%-17.0%) in the
      postintervention cohort.

PMID- 29450939
TI  - Unexplained infertility patients present the mostly impaired levels of
      progesterone receptors: Prospective observational study.
AB  - PROBLEM: Tauo assess the endometrial expression of progesterone receptors in
      various subgroups of infertile women during implantation window. MUETHODS: A
      prospective observational study was performed during March 2013-February 2017.
      Infertile women were categorized to those with tubal factor, ovarian failure,
      endometriosis or unexplained infertility. Endometrial biopsy was obtained on 7th
      8th postovulatory day. Total progesterone receptors' PR(A + B) and type-B
      receptors' (PR-B) expression were compared between all categories of infertile
      and fruitful controls. RESULTS: There were overall 30 patients with tubal factor
      infertility (group 1), 30 with ovarian failure (group 2), 20 with endometriosis
      (group 3) and 20 with unexplained infertility (group 4). The control group
      consisted of 30 fertile patients. Patients with unexplained infertility presented
      the lowest levels of epithelial endometrial expression both regarding PR(A + B)
      and PR-B receptors. PgR(A + B) h-score in luminal epithelial cells was 106.4 +/-
      14.7 for cases with unexplained infertility vs 219.7 +/- 15.8 for controls (P <
      .001). Similarly, PgR(A + B) h-score in glandular epithelial cells was 109.7 +/-
      13.9 vs 220.1 +/- 17.2 (P < .001). Relative remarks were made for type-B
      progesterone receptors. CONCLUSION: Epsilonndometrial expression of progesterone
      receptors is impaired in women with unexplained infertility. Therapeutic
      strategies targeting on improving progesterone receptors' expression may
      significantly affect final reproductive outcome.

PMID- 29450940
TI  - Statistical inference in brain graphs using threshold-free network-based
      statistics.
AB  - The description of brain networks as graphs where nodes represent different brain
      regions and edges represent a measure of connectivity between a pair of nodes is
      an increasingly used approach in neuroimaging research. The development of
      powerful methods for edge-wise group-level statistical inference in brain graphs
      while controlling for multiple-testing associated false-positive rates, however,
      remains a difficult task. In this study, we use simulated data to assess the
      properties of threshold-free network-based statistics (TFNBS). The TFNBS combines
      threshold-free cluster enhancement, a method commonly used in voxel-wise
      statistical inference, and network-based statistic (NBS), which is frequently
      used for statistical analysis of brain graphs. Unlike the NBS, TFNBS generates
      edge-wise significance values and does not require the a priori definition of a
      hard cluster-defining threshold. Other test parameters, nonetheless, need to be
      set. We show that it is possible to find parameters that make TFNBS sensitive to
      strong and topologically clustered effects, while appropriately controlling false
      positive rates. Our results show that the TFNBS is an adequate technique for the
      statistical assessment of brain graphs.

PMID- 29450941
TI  - Hematogenous Dissemination of Mesenchymal Stem Cells from Endometriosis.
AB  - Endometriosis is ectopic growth of endometrial tissue traditionally thought to
      arise through retrograde menstruation. We aimed to determine if cells derived
      from endometriosis could enter vascular circulation and lead to hematogenous
      dissemination. Experimental endometriosis was established by transplanting
      endometrial tissue from DsRed+ mice into the peritoneal cavity of DsRed- mice.
      Using flow cytometry, we identified DsRed+ cells in blood of animals with
      endometriosis. The circulating donor cells expressed CXCR4 and mesenchymal stem
      cell (MSC) biomarkers, but not hematopoietic stem cell markers. Nearly all the
      circulating endometrial stem cells originated from endometriosis rather than from
      the uterus. Cells expressing DsRed, CXCR4, and MSCs markers were identified in
      the peritoneal wall and surrounding vessels of recipient mice, contributing to
      both endometriosis and angiogenesis. Cells originating in endometriosis lesions
      migrated and implanted in lung tissue and displayed makers of differentiation,
      indicating retained multipotency. In vitro these cells demonstrated multipotency
      and were able to differentiate into adipogenic, osteogenic, and chondrogenic
      lineages. Endometriosis lesions also expressed high levels of CXCL12, the CXCR4
      receptor ligand. Serum CXCL12 levels were greater than in sham control mice. In
      humans with endometriosis, serum CXCL12 levels were significantly higher than
      controls, suggesting that the CXCL12/CXCR4 axis is operational in women with
      spontaneous endometriosis as well. Stem cells, rather than differentiated cells
      from endometriosis, enter the circulation in response to CXCL12. We identify an
      endometriosis-derived stem cell population, a potential mechanism of
      dissemination of this disease and a potential target for treatment of
      endometriosis. Stem Cells 2018;36:881-890.

PMID- 29450942
TI  - Multivariate analysis of cytokine profiles in pregnancy complications.
AB  - PROBLEM: The immunoregulation to tolerate the semiallogeneic fetus during
      pregnancy includes a harmonious dynamic balance between anti- and pro
      inflammatory cytokines. Several earlier studies reported significantly different
      levels and/or ratios of several cytokines in complicated pregnancy as compared to
      normal pregnancy. However, as cytokines operate in networks with potentially
      complex interactions, it is also interesting to compare groups with multi
      cytokine data sets, with multivariate analysis. Such analysis will further
      examine how great the differences are, and which cytokines are more different
      than others. METHODS: Various multivariate statistical tools, such as Cramer
      test, classification and regression trees, partial least squares regression
      figures, 2-dimensional Kolmogorov-Smirmov test, principal component analysis and
      gap statistic, were used to compare cytokine data of normal vs anomalous groups
      of different pregnancy complications. RESULTS: Multivariate analysis assisted in
      examining if the groups were different, how strongly they differed, in what ways
      they differed and further reported evidence for subgroups in 1 group (pregnancy
      induced hypertension), possibly indicating multiple causes for the complication.
      CONCLUSION: This work contributes to a better understanding of cytokines
      interaction and may have important implications on targeting cytokine balance
      modulation or design of future medications or interventions that best direct
      management or prevention from an immunological approach.

PMID- 29450943
TI  - Cortical projections to the superior colliculus in grey squirrels (Sciurus
      carolinensis).
AB  - The superior colliculus is an important midbrain structure involved with
      integrating information from varying sensory modalities and sending motor signals
      to produce orienting movements towards environmental stimuli. Because of this
      role, the superior colliculus receives a multitude of sensory inputs from a wide
      variety of subcortical and cortical structures. Proportionately, the superior
      colliculus of grey squirrels is among the largest in size of all studied mammals,
      suggesting the importance of this structure in the behavioural characteristics of
      grey squirrels. Yet, our understanding of the connections of the superior
      colliculus in grey squirrels is lacking, especially with respect to possible
      cortical influences. In this study, we placed anatomical tracer injections within
      the medial aspect of the superior colliculus of five grey squirrels (Sciurus
      carolinensis) and analysed the areal distribution of corticotectal projecting
      cells in flattened cortex. V1 projections to the superior colliculus were studied
      in two additional animals. Our results indicate that the superior colliculus
      receives cortical projections from visual, higher order somatosensory, and higher
      order auditory regions, as well as limbic, retrosplenial and anterior cingulate
      cortex. Few, if any, corticotectal projections originate from primary motor,
      primary somatosensory or parietal cortical regions. This distribution of inputs
      is similar to the distribution of inputs described in other rodents such as rats
      and mice, yet the lack of inputs from primary somatosensory and motor cortex is
      features of corticotectal inputs more similar to those observed in tree shrews
      and primates, possibly reflecting a behavioural shift from somatosensory
      (vibrissae) to visual navigation.

PMID- 29450945
TI  - Clinical application of 3D technology for tooth autotransplantation: A case
      report.
AB  - This report presents two cases of tooth autotransplantation using cone-beam
      computed tomography (CBCT), the three-dimensional (3D) simulation dental planning
      software and a computer-aided rapid prototyping (CARP) model. Two hopeless teeth
      of adult patients were replaced as their third molar teeth. Before deciding the
      autotransplantation, diagnostic CBCT images were acquired and imported to
      SimPlant software. The SimPlant dental program was used for surgical simulation
      prior to autotransplantation, which created 3D images of the available donor
      teeth and recipient site tooth and superimposed the images to display their
      morphological similarity. Efficient modification of the recipient socket was
      designed preoperatively. The CARP model of the donor tooth was prepared as a
      substitute for the donor tooth that would be fit into the new recipient socket
      during bone preparation. Autotransplantation was favourably performed in 5-6 min.
      Transplanted teeth healed up without clinical abnormality. The postoperative
      follow-up time was up to 6 years.

PMID- 29450944
TI  - NRF2 addiction in cancer cells.
AB  - The Kelch-like ECH-associated protein 1/nuclear factor erythroid-derived 2-like 2
      (KEAP1-NRF2) system is a pivotal defense mechanism against oxidative and
      electrophilic stress. Although transient NRF2 activation in response to stress is
      beneficial for health, persistent NRF2 activation in cancer cells has deleterious
      effects on cancer-bearing hosts by conferring therapeutic resistance and
      aggressive tumorigenic activity on cancer cells. Because NRF2 increases the
      antioxidant and detoxification capability of cancer cells, persistently high
      levels of NRF2 activity enhance therapeutic resistance of cancer cells. NRF2 also
      drives metabolic reprogramming to establish cellular metabolic processes that are
      advantageous for cell proliferation in cooperation with other oncogenic pathways.
      As a result of these advantages, cancer cells with persistent activation of NRF2
      often develop "NRF2 addiction" and show malignant phenotypes leading to poor
      prognoses in cancer patients. Inhibition of NRF2 is a promising therapeutic
      approach for NRF2-addicted cancers and NRF2 inhibitors are being actively
      developed. However, giving systemic NRF2 inhibitors might have undesirable
      effects on cancer-bearing hosts, considering the central roles of NRF2 in
      cytoprotection. To avoid these side-effects, new therapeutic targets besides NRF2
      for NRF2-addicted cancers have been actively explored. This review introduces
      recent studies describing the development and characterization of NRF2-addicted
      cancers, as well as their potential therapeutic targets. Expected advances in
      diagnostic and therapeutic interventions for NRF2-addicted cancers are also
      discussed.

PMID- 29450947
TI  - Effects of climate on soil phosphorus cycle and availability in natural
      terrestrial ecosystems.
AB  - Climate is predicted to change over the 21st century. However, little is known
      about how climate change can affect soil phosphorus (P) cycle and availability in
      global terrestrial ecosystems, where P is a key limiting nutrient. With a global
      database of Hedley P fractions and key-associated physiochemical properties of
      760 (seminatural) natural soils compiled from 96 published studies, this study
      evaluated how climate pattern affected soil P cycle and availability in global
      terrestrial ecosystems. Overall, soil available P, indexed by Hedley labile
      inorganic P fraction, significantly decreased with increasing mean annual
      temperature (MAT) and precipitation (MAP). Hypothesis-oriented path model
      analysis suggests that MAT negatively affected soil available P mainly by
      decreasing soil organic P and primary mineral P and increasing soil sand content.
      MAP negatively affected soil available P both directly and indirectly through
      decreasing soil primary mineral P; however, these negative effects were offset by
      the positive effects of MAP on soil organic P and fine soil particles, resulting
      in a relatively minor total MAP effect on soil available P. As aridity degree was
      mainly determined by MAP, aridity also had a relatively minor total effect on
      soil available P. These global patterns generally hold true irrespective of soil
      depth (<=10 cm or >10 cm) or site aridity index (<=1.0 or >1.0), and were also
      true for the low-sand (<=50%) soils. In contrast, available P of the high-sand
      (>50%) soils was positively affected by MAT and aridity and negatively affected
      by MAP. Our results suggest that temperature and precipitation have contrasting
      effects on soil P availability and can interact with soil particle size to
      control soil P availability.

PMID- 29450946
TI  - Downregulation of leucine-rich repeats and immunoglobulin-like domains 1 by
      microRNA-20a modulates gastric cancer multidrug resistance.
AB  - Multidrug resistance (MDR) significantly restricts the clinical efficacy of
      gastric cancer (GC) chemotherapy, and it is critical to search novel targets to
      predict and overcome MDR. Leucine-rich repeats and immunoglobulin-like domains 1
      (LRIG1) has been proved to be correlated with drug resistance in several cancers.
      The present study revealed that LRIG1 was overexpressed in chemosensitive GC
      tissues and decreased expression of LRIG1 predicted poor survival in GC patients.
      We observed that upregulation of LRIG1 enhanced chemosensitivity in GC cells.
      Interestingly, miR-20a, which was overexpressed in GC MDR cell lines and tissues,
      was identified to regulate LRIG1 expression by directly targeting its 3'
      untranslated region. We also found that inhibition of miR-20a suppressed GC MDR,
      and upregulation showed opposite effects. Moreover, we demonstrated that the miR
      20a/LRIG1 axis regulated GC cell MDR through epidermal growth factor receptor
      (EGFR)-mediated PI3K/AKT and MAPK/ERK signaling pathways. Finally, LRIG1
      expression in human GC tissues is inversely correlated with miR-20a and EGFR.
      Taken together, the newly identified miR-20a/LRIG1/EGFR link provides insight
      into the MDR process of GC, and targeting this axis represents a novel potential
      therapeutic strategy to block GC chemoresistance.

PMID- 29450948
TI  - ADUC Prizes: U.-P. Apfel, P. Heretsch, O. Holloczki / Carl Duisberg Memorial
      Award: B. Morandi / Elected to the Academie des Sciences: E. Charpentier, J.
      Cossy, I. Marek / Max Delbruck Junior Prize: S. Disch / Novartis Early Career
      Award: B. Morandi and R. R. Knowles.

PMID- 29450949
TI  - Transcription factors PRE3 and WOX11 are involved in the formation of new lateral
      roots from secondary growth taproot in A. thaliana.
AB  - The spatial deployment of lateral roots determines the ability of a plant to
      interact with the surrounding environment for nutrition and anchorage. This paper
      shows that besides the pericycle, the vascular cambium becomes active in
      Arabidopsis thaliana taproot at a later stage of development and is also able to
      form new lateral roots. To demonstrate the above, we implemented a two-step
      approach in which the first step leads to development of a secondary structure in
      A. thaliana taproot, and the second applies a mechanical stress on the vascular
      cambium to initiate formation of a new lateral root primordium. GUS staining
      showed PRE3, DR5 and WOX11 signals in the cambial zone of the root during new
      lateral root formation. An advanced level of wood formation, characterized by the
      presence of medullar rays, was achieved. Preliminary investigations suggest the
      involvement of auxin and two transcription factors (PRE3/ATBS1/bHLH135/TMO7 and
      WOX11) in the transition of some vascular cambium initials from a role as
      producers of xylem/phloem mother cells to founder cells of a new lateral root
      primordium.

PMID- 29450950
TI  - Imaging Nano-Bio Interactions in the Kidney: Toward a Better Understanding of
      Nanoparticle Clearance.
AB  - All clear! Highlighted is work aimed at a better understanding of nano-bio
      interactions for rational design of renal-clearable nanoparticles in diseased
      kidneys. Renal clearance of ultra-small gold nanoparticles (AuNPs) is not only
      dependent upon the Choi criteria but is also affected by the microphysiological
      structure of the glomerular barrier and the pathophysiological changes in the
      nephron.

PMID- 29450951
TI  - Studies on lead and cadmium toxicity in Dianthus carthusianorum calamine ecotype
      cultivated in vitro.
AB  - Information on metallophytes during reclamation of land contaminated with heavy
      metals is sparse. We investigated the response of D. carthusianorum calamine
      ecotype to Pb and Cd stress. We focused on in vitro selection of tolerant plant
      material for direct use in chemically degraded areas. Shoot cultures were treated
      with various concentrations of Pb or Cd ions. Plantlet status was estimated as
      micropropagation efficiency, growth tolerance index (GTI) and through
      physiological analysis. Moreover, determination of plant Pb, Cd and other
      elements was performed. The application of Pb(NO3 )2 resulted in stronger growth
      inhibition than application of CdCl2 . In the presence of Pb ions, a reduction
      was observed of both, the micropropagation coefficient to 1.1-1.8 and the GTI to
      48%. In contrast, Cd ions had a positive influence on tested cultures, expressed
      as an increase of GTI up to 243% on medium enriched with 1.0 MUm CdCl2 .
      Moreover, photosynthetic pigment content in shoots cultivated on media with CdCl2
      was higher than in control treatment. The adaptation to Cd was associated with
      decreased accumulation of phenols in the order: 0.0 MUm > 1.0 MUm > 3.0 MUm > 5.5
      MUm CdCl2 . It seems that high tolerance to Cd is related to K uptake, which is
      involved in antioxidant defence. This work presents an innovative approach to the
      impact of Cd ions on plant growth and suggests a potential biological role of
      this metal in species from metalliferous areas.

PMID- 29450952
TI  - Two Stereoinduction Events in One C-H Activation Step: A Route towards Terphenyl
      Ligands with Two Atropisomeric Axes.
AB  - Herein we disclose the synthesis of original chiral scaffolds-ortho-orientated
      terphenyls presenting two atropisomeric Ar-Ar axes. These unusual structures were
      built up by using the C-H activation approach, and remarkably, both chiral axes
      were controlled with excellent stereoselectivity in a single transformation.
      During the reaction, not only does atroposelective functionalization of a biaryl
      precursor occur to establish one stereogenic axis, but an unprecedented atropo
      stereoselective C-H arylation also takes place to generate the second stereogenic
      element. These enantiomerically pure ortho-terphenyls show an original
      tridimensional structure and thus constitute a unique foundation for building up
      a library of enantiomerically pure bidentate ligands, such as the new ligands S/N
      Biax and diphosphine BiaxPhos.

PMID- 29450953
TI  - Factors influencing seedling emergence of three global invaders in greenhouses
      representing major eco-regions of the world.
AB  - Successful germination and seedling emergence in new environments are crucial
      first steps in the life history of global plant invaders and thus play a key role
      in processes of range expansion. We examined the germination and seedling
      emergence success of three global plant invaders - Lupinus polyphyllus, Senecio
      inaequidens and Verbascum thapsus - in greenhouses and climate chambers under
      climate regimes corresponding to seven eco-regions. Seed materials were collected
      from one non-native population for L. polyphyllus and S. inaequidens, and from 12
      populations for V. thapsus (six natives and six non-natives). Experimental
      climates had significant effects on species responses. No species germinated in
      the dry (humidity <= 50%) and cool (<= 5  degrees C) experimental climates. But
      all species germinated and emerged in two moderately cool (12-19  degrees C) and
      in three warm (24-27  degrees C) experimental climates. In general, V. thapsus
      showed higher fitness than S. inaequidens and L. polyphyllus. The climate of the
      seed source region influenced responses of native and non-native populations of
      V. thapsus. Non-native populations of V. thapsus, originating from the warmer
      seed source, showed higher performance in warm experimental climates and lower
      performance in moderately cool experimental climates compared to native
      populations. Responses of V. thapsus populations were also related to
      precipitation of the seed source region in moderately dry experimental climates.
      The warm, semi-arid and humid experimental climates are suitable for the crucial
      first steps of invasion success for L. polyphyllus, S. inaequidens and V.
      thapsus. The species adaptation to its source region modified the responses of
      our studied plants under different experimental climates representing major eco
      regions of the world.

PMID- 29450954
TI  - Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder.
AB  - OBJECTIVES: Increasing evidence points to the harmful effects of long-term
      benzodiazepine treatment. Our objective was to study the incidence of, and
      predictors for, long-term use of benzodiazepines and Z-drugs in bipolar disorder.
      METHODS: We conducted a population-based cohort study, using data from Swedish
      national registers. Swedish residents aged 18-75 years with a recorded diagnosis
      of bipolar disorder or mania between July 2006 and December 2012, and no history
      of benzodiazepine/Z-drug use in the past year, were included. Patients were
      followed for 1 year with regard to prescription fills of benzodiazepines/Z-drugs.
      Initiators were followed for another year during which continuous use for >6
      months was defined as "long-term". Patient and prescription characteristics were
      investigated as potential predictors for long-term use in multivariate logistic
      regression models. RESULTS: Out of the 21 883 patients included, 29% started
      benzodiazepine/Z-drug treatment, of whom one in five became long-term users.
      Patients who were prescribed clonazepam or alprazolam had high odds for
      subsequent long-term use (adjusted odds ratios [aORs] 3.78 [95% confidence
      interval (CI) 2.24-6.38] and 2.03 [95% CI 1.30-3.18], respectively), compared to
      those prescribed diazepam. Polytherapy with benzodiazepines/Z-drugs also
      predicted long-term use (aOR 2.46, 95% CI 1.79-3.38), as did age >=60 years (aOR
      1.93, 95% CI 1.46-2.53, compared to age <30 years), and concomitant treatment
      with psychostimulants (aOR 1.78, 95% CI 1.33-2.39). CONCLUSIONS: The incidence of
      subsequent long-term use among bipolar benzodiazepine initiators is high.
      Patients on clonazepam, alprazolam or benzodiazepine/Z-drug polytherapy have the
      highest risk of becoming long-term users, suggesting that these treatments should
      be used restrictively.

PMID- 29450955
TI  - N-Functionalized Ferrocenes: Subvalent Group XIV Element Chlorides and tert
      Butyllithium-Induced C-C Bond Cleavage under Mild Conditions.
AB  - The ferrocene derivative (eta5 -Cp)Fe{eta5 -C5 H3 -1-(ArNCH)-2-(CH2 NMe2 )} (1;
      Ar=2,6-iPr2 C6 H3 )) reacts diastereoselectively with LiR by carbolithiation and
      subsequent hydrolysis to give (eta5 -Cp)Fe{eta5 -C5 H3 -1-(ArHNCHR)-2-(CH2 NMe2
      )} (3: R=tBu; 4: R=Ph; 5: R=Me) in high yields. For R=tBu, the organolithium
      derivative (eta5 -Cp)Fe{eta5 -C5 H3 -1-(ArLiNCHR)-2-(CH2 NMe2 )} (2) was
      isolated. Compound 2 reacts with GeCl2 ?dioxane and SnCl2 to give the metallylene
      amide chlorides (eta5 -Cp)Fe{eta5 -C5 H3 -1-(ArMNCHtBu)-2-(CH2 NMe2 )} 6 (M=GeCl)
      and 7 (M=SnCl), respectively, which each contain three stereogenic centers. The
      potential of 7 as a ligand in transition-metal chemistry is demonstrated by
      formation of its complex (eta5 -Cp)Fe{eta5 -C5 H3 -1-(ArMNCHtBu)-2-(CH2 NMe2 )}
      [9, M= Sn(Cl)W(CO)5 ]. Treatment of 3 with tert-butyllithium at room temperature
      causes an unprecedented carbon-carbon bond cleavage whereas under kinetic
      control, lithiation at the Cp-3 position takes place, which leads to the
      isolation of (eta5 -Cp)Fe{eta5 -C5 H3 -1-(ArHNCHtBu)-2-(CH2 NMe2 )-3-SiMe3 }
      (10).

PMID- 29450956
TI  - An Organic Mixed-Valence Ligand for Multistate Redox-Active Coordination
      Networks.
AB  - The multistate redox-active/multi-interactive ligand 5,5',8,8'-tetra(4-pyridyl)
      2,2'-(1,4-phenylene)bis-1H-perimidine (H2 TPP) was designed and synthesized. H2
      TPP undergoes four one-electron oxidation steps, and was used for the preparation
      of a multistate redox-active coordination network in a solid-liquid interface
      reaction using molten Cd2+ salts. The multiple redox states of H2 TPP were
      confirmed spectroscopically by stepwise four-electron oxidation. Spectroscopic
      analysis indicated that the mixed-valence states of the ligand are class II on
      the UV/Vis/NIR timescale and borderline class II/class III on the ESR timescale.

PMID- 29450957
TI  - Towards better blood pressure: Do non-pharmacological strategies provide the
      right path?

PMID- 29450958
TI  - Use of physician-recommended non-pharmacological strategies for hypertension
      control among hypertensive patients.
AB  - This study aims to evaluate the 4 non-pharmacological strategies adopted by
      patients for hypertension control and patient characteristics that affect the
      choice of strategies. Four thousand hypertensive patients aged >=18 years were
      selected from the National Health and Nutrition Examination Survey. Odds ratios
      of the choice of strategies were analyzed using weighted logistic models.
      Clinical recommendations of non-pharmacological strategies for hypertension
      control were relatively low. More exercise was the least frequent strategy used
      for hypertension control. More patients reported using >=3 strategies than using
      <=2 strategies (79.1% vs 20.9%, P < .0001). Non-Hispanic blacks were more likely
      to use each individual strategy and to use >=3 strategies simultaneously.
      Patients with obesity and diabetes were less likely to attempt weight control or
      more exercise, but more likely to use >=3 strategies than peers. Educational
      programs should be developed to enhance physician's advice for lifestyle
      modifications and to increase patient's acceptance of physical activity.

PMID- 29450959
TI  - Relation of uric acid level to rapid kidney function decline and development of
      kidney disease: The Jackson Heart Study.
AB  - Whether elevated uric acid (UA) is an independent risk factor for chronic kidney
      disease (CKD) is not well established. The authors evaluated the relationship of
      UA with rapid kidney function decline (RKFD) and incident CKD among 3702 African
      Americans (AAs) in the Jackson Heart Study with serum UA levels measured at
      baseline exam (2000-2004). RKFD was defined as >= 30% eGFR loss and incident CKD
      as development of eGFR < 60 mL/min/1.73 m2 with a >= 25% decline in eGFR between
      baseline and exam 3 (2009-2013). RKFD and CKD were found in 11.4% and 7.5% of the
      participants, respectively. In a fully adjusted model, the odds of RKFD (OR, 1.8;
      95% CI, 1.25-2.49) and incident CKD (OR, 2.00; 95% CI, 1.31-3.06) were
      significantly higher among participants in the top UA quartile vs bottom
      quartile. In the JHS, elevated UA was significantly associated with RKFD and
      incident CKD.

PMID- 29450960
TI  - Effect of flower orientation on the male and female traits of Myrtillocactus
      geometrizans (Cactaceae).
AB  - Intra-individual variation in the production and size of reproductive traits has
      been documented in columnar cacti, being higher in equator-facing flowers. Such
      variation is attributed to the high amount of PAR intercepted by stems oriented
      towards the equator. Most studies focused on this phenomenon have documented the
      existence of intra-individual variation on traits associated with the female
      function; however, its impact on traits associated with the male function has
      been neglected. We tested the hypothesis that equator-facing flowers of
      Myrtillocactus geometrizans exhibit higher values on traits associated with both
      male and female functions than flowers facing against it. Number and size of
      anthers and ovaries, pollen:ovule ratio and number and quality of pollen grains
      (diameter, germinability, viability and pollen tube length) were estimated from
      reproductive structures facing north and south, and compared with t-tests between
      orientations. Number of anthers per flower, number of pollen grains per anther
      and per floral bud; pollen size, viability and germinability; pollen tube length;
      ovary length and pollen:ovule ratio were significantly higher in reproductive
      structures oriented towards the south (i.e. equator). These findings suggest that
      intra-individual variation in floral traits of M. geometrizans might be
      associated with different availability of resources in branches with contrasting
      orientation. Our results provide new evidence of the existence of a response to
      an orientation-dependent extrinsic gradient. To our knowledge, this is the first
      study documenting the existence of intra-individual variation on pollen quality
      and P:O ratio in Cactaceae species.

PMID- 29450962
TI  - Renal resistive index for renovascular hypertension: In the quest of the Holy
      Grail.

PMID- 29450961
TI  - Volumetric-based image guidance is superior to marker-based alignments for
      stereotactic body radiotherapy of prostate cancer.
AB  - PURPOSES: The aim of this study was to evaluate a dual marker-based and soft
      tissue based image guidance for inter-fractional corrections in stereotactic body
      radiotherapy (SBRT) of prostate cancer. METHODS/MATERIALS: We reviewed 18
      patients treated with SBRT for prostate cancer. An endorectal balloon was
      inserted at simulation and each treatment. Planning margins were 3 mm/0 mm
      posteriorly. Prior to each treatment, a dual image guidance protocol was applied
      to align three makers using stereoscopic x ray images and then to the soft tissue
      using kilo-voltage cone beam CT (kV-CBCT). After treatment, prostate (CTV),
      rectal wall, and bladder were delineated on each kV-CBCT, and delivered dose was
      recalculated. Dosimetric endpoints were analyzed, including V36.25 Gy for
      prostate, and D0.03 cc for bladder and rectal wall. RESULTS: Following initial
      marker alignment, additional translational shifts were applied to 22 of 84
      fractions after kV-CBCT. Among the 22 fractions, ten fractions exceeded 3 mm
      shifts in any direction, including one in the left-right direction, four in the
      superior-inferior direction, and five in the anterior-posterior direction. With
      and without the additional kV-CBCT shifts, the average V36.25 Gy of the prostate
      for the 22 fractions was 97.6 +/- 2.6% with the kV x ray image alone, and was
      98.1 +/- 2.4% after applying the additional kV-CBCT shifts. The improvement was
      borderline statistical significance using Wilcoxon signed-rank test (P = 0.007).
      D0.03 cc was 45.8 +/- 6.3 Gy vs. 45.1 +/- 4.9 Gy for the rectal wall; and 49.5 +/
      8.6 Gy vs. 49.3 +/- 7.9 Gy for the bladder before and after applying kV-CBCT
      shifts. CONCLUSIONS: Marker-based alignment alone is not sufficient. Additional
      adjustments are needed for some patients based kV-CBCT.

PMID- 29450963
TI  - Multicellular Tumor Spheroids (MCTS) as a 3D In Vitro Evaluation Tool of
      Nanoparticles.
AB  - Multicellular tumor spheroid models (MCTS) are often coined as 3D in vitro models
      that can mimic the microenvironment of tissues. MCTS have gained increasing
      interest in the nano-biotechnology field as they can provide easily accessible
      information on the performance of nanoparticles without using animal models.
      Considering that many countries have put restrictions on animals testing, which
      will only tighten in the future as seen by the recent developments in the
      Netherlands, 3D models will become an even more valuable tool. Here, an overview
      on MCTS is provided, focusing on their use in cancer research as most
      nanoparticles are tested in MCTS for treatment of primary tumors. Thereafter,
      various types of nanoparticles-from self-assembled block copolymers to inorganic
      nanoparticles, are discussed. A range of physicochemical parameters including the
      size, shape, surface chemistry, ligands attachment, stability, and stiffness are
      found to influence nanoparticles in MCTS. Some of these studies are complemented
      by animal studies confirming that lessons from MCTS can in part predict the
      behaviour in vivo. In summary, MCTS are suitable models to gain additional
      information on nanoparticles. While not being able to replace in vivo studies,
      they can bridge the gap between traditional 2D in vitro studies and in vivo
      models.

PMID- 29450964
TI  - Imparting Designer Biorecognition Functionality to Metal-Organic Frameworks by a
      DNA-Mediated Surface Engineering Strategy.
AB  - Surface functionality is an essential component for processing and application of
      metal-organic frameworks (MOFs). A simple and cost-effective strategy for DNA
      mediated surface engineering of zirconium-based nanoscale MOFs (NMOFs) is
      presented, capable of endowing them with specific molecular recognition
      properties and thus expanding their potential for applications in nanotechnology
      and biotechnology. It is shown that efficient immobilization of functional DNA on
      NMOFs can be achieved via surface coordination chemistry. With this strategy, it
      is demonstrated that such porphyrin-based NMOFs can be modified with a DNA
      aptamer for targeting specific cancer cells. Furthermore, the DNA-NMOFs can
      facilitate the delivery of therapeutic DNA (e.g., CpG) into cells for efficient
      recognition of endosomal Toll-like receptor 9 and subsequent enhanced
      immunostimulatory activity in vitro and in vivo. No apparent toxicity is observed
      with systemic delivery of the DNA-NMOFs in vivo. Overall, these results suggest
      that the strategy allows for surface functionalization of MOFs with different
      functional DNAs, extending the use of these materials to diverse applications in
      biosensor, bioimaging, and nanomedicine.

PMID- 29450965
TI  - Risk of early-onset breast cancer among women exposed to thoracic computed
      tomography in pregnancy or early postpartum.
AB  - : Essentials Tests for pulmonary embolism expose women to low-dose radiation.
      5859 pregnancies had a thoracic computed tomography (T-CT) vs. 1.3 million who
      did not. The adjusted hazard ratio for breast cancer was 1.17 (95% confidence
      interval 0.80-1.70). The long-term risk of breast cancer among women who had a T
      CT remains unknown. SUMMARY: Background The risk of breast cancer may be higher
      with direct exposure to ionizing radiation from thoracic computed tomography (CT)
      during pregnancy or the postpartum. We evaluated the short-term risk of maternal
      breast cancer after exposure to thoracic CT during these periods. Methods We
      completed a retrospective population-based cohort study of all deliveries between
      1995 and 2014 using universal healthcare databases in the province of Ontario,
      Canada. The main exposure was thoracic CT in pregnancy or <= 42 days postpartum.
      The passive exposure was ventilation-perfusion scintigraphy (VQ) scan in
      pregnancy or <= 42 days postpartum. Each was compared to pregnancies unexposed to
      thoracic CT or VQ scan. The primary study outcome was newly diagnosed breast
      cancer starting 366 days post-index delivery date. Results A total of 5859
      pregnancies were exposed to thoracic CT, 4075 to VQ scan and 1 292 059 to
      neither. Starting from 1 year after the index delivery, the median duration of
      follow-up was 5.9, 7.3 and 11.1 years, respectively. A total of 10 129 women were
      diagnosed with breast cancer, of whom 9039 (89.2%) were aged <= 50 years. There
      were 27 new cases of breast cancer (7.1 per 10 000 person-years) following
      thoracic CT vs. 10 080 (7.0 per 10 000 person-years) among the unexposed, an
      adjusted hazard ratio (HR) of 1.17 (95% confidence interval [CI], 0.80-1.70).
      Following VQ scan exposure, the incidence rate of breast cancer was 7.0 per 10
      000 person-years, an adjusted HR of 1.23 (95% CI 0.81-1.87), compared with the
      unexposed cohort. Conclusion Exposure to thoracic CT during pregnancy or the
      postpartum was not associated with an increased short-term risk of maternal
      breast cancer. The long-term risk should be studied.

PMID- 29450966
TI  - Highly Uniform Resistive Switching Properties of Solution-Processed Silver
      Embedded Gelatin Thin Film.
AB  - The silver-embedded gelatin (AgG) thin film produced by the solution method of
      metal salts dissolved in gelatin is presented. Its simple fabrication method
      ensures the uniform distribution of Ag dots. Memory devices based on AgG exhibit
      good device performance, such as the ON/OFF ratio in excess of 105 and the
      coefficient of variation in less of 50%. To further investigate the position of
      filament formation and the role of each element, current sensing atomic force
      microscopy (CSAFM) analysis as well as elemental line profiles across the two
      different conditions in the LRS and HRS are analyzed. The conductive and
      nonconductive regions in the current map of the CSAFM image show that the
      conductive filaments occur in the AgG layer around Ag dots. The migration of
      oxygen ions and the redox reaction of carbon are demonstrated to be the driving
      mechanism for the resistive switching of AgG memory devices. The results show
      that dissolving metal salts in gelatin is an effective way to achieve high
      performance organic-electronic applications.

PMID- 29450967
TI  - Carotid atherosclerosis and the association between nocturnal blood pressure
      dipping and cardiovascular events.
AB  - The impact of a nondipping blood pressure (BP) pattern, defined as (awake
      systolic BP - sleep systolic BP)/awake systolic BP < 0.1, on cardiovascular
      events in populations with different degrees of carotid atherosclerosis is
      uncertain. The authors hypothesized that a nondipping BP pattern would show
      differential predictive power for cardiovascular events, including total
      cardiovascular death, sudden death, nonfatal cardiovascular events, and nonfatal
      stroke, between populations with and without carotid atherosclerosis. To test
      this hypothesis, the authors analyzed 493 patients (mean age 67.9 years, 47.5%
      men) from the J-HOP (Japan Morning Surge-Home Blood Pressure) study for whom
      ambulatory BP monitoring and carotid intima-media thickness data were available.
      Twenty-nine cardiovascular events occurred during follow-up (1867 person-years).
      A nondipping BP pattern was independently associated with cardiovascular events
      in the population without carotid atherosclerosis, defined as carotid intima
      media thickness < 1.1 mm after adjustment for other cardiovascular risk factors
      including age, sex, diabetes mellitus, chronic kidney disease, and 24-hour
      systolic BP (hazard ratio, 8.15; 95% confidence interval, 1.76-37.78 [P < .01]).
      This association was not found in the population with carotid intima-media
      thickness >= 1.1 mm. Therefore, in the hypertensive population without carotid
      atherosclerosis, physicians should consider ambulatory BP monitoring to determine
      the nocturnal BP pattern as an alternative approach to assessing cardiovascular
      events.

PMID- 29450968
TI  - Knowledge about traumatic dental injuries in the permanent dentition: A survey of
      Lithuanian dentists.
AB  - BACKGROUND/AIMS: In Lithuania, dental trauma cases are often treated by general
      dentists, but it is unknown whether their age, self-evaluation of trauma
      knowledge and practice location can predict their actual knowledge and management
      of trauma cases. The aim of this study was to evaluate whether these factors can
      be used to predict the actual knowledge and management of trauma cases. METHODS:
      A 2-part questionnaire included 17 multiple-choice questions about practitioners'
      demographics, their self-evaluated knowledge and how frequently they treated
      traumatized permanent teeth as well as 13 clinical scenarios reflecting a variety
      of clinical trauma cases and their complications. A total of 980 randomly
      selected general dentists, representing 5 Lithuanian counties, participated in
      the study. RESULTS: The response rate was 59.4% (n = 582). Overall, 82.3% of
      general dentists reported that they treated only a few dental trauma cases and
      14.4% chose to refer their patients; 55.1% of dentists considered their dental
      traumatology knowledge to be sufficient but incomplete and 34.0% self-evaluated
      their knowledge as insufficient. The most knowledge (based on self-evaluation)
      was reported by the younger dentists (<=50 years; P = .004). The mean correct
      knowledge score was 7.6 +/- 2.2 of the 13 clinical scenarios. Both bivariate and
      multivariate analyses showed that greater trauma-related knowledge was associated
      with a younger age. Better knowledge was observed amongst the dentists who self
      evaluated their own knowledge as sufficient or as comprehensive. CONCLUSION:
      Lithuanian general dentists have insufficient dental traumatology knowledge.
      Better knowledge was observed amongst younger dentists (<=50 years).

PMID- 29450969
TI  - Layer-by-Layer Decoupling of Twisted Graphene Sheets Epitaxially Grown on a Metal
      Substrate.
AB  - The electronic properties of graphene can be efficiently altered upon interaction
      with the underlying substrate resulting in a dramatic change of charge carrier
      behavior. Here, the evolution of the local electronic properties of epitaxial
      graphene on a metal upon the controlled formation of multilayers, which are
      produced by intercalation of atomic carbon in graphene/Ir(111), is investigated.
      Using scanning tunneling microscopy and Landau-level spectroscopy, it is shown
      that for a monolayer and bilayers with small-angle rotations, Landau levels are
      fully suppressed, indicating that the metal-graphene interaction is largely
      confined to the first graphene layer. Bilayers with large twist angles as well as
      twisted trilayers demonstrate a sequence of pronounced Landau levels
      characteristic for a free-standing graphene monolayer pointing toward an
      effective decoupling of the top layer from the metal substrate. These findings
      give evidence for the controlled preparation of epitaxial graphene multilayers
      with a different degree of decoupling, which represent an ideal platform for
      future electronic and spintronic applications.

PMID- 29450970
TI  - Direct Imaging of Space-Charge Accumulation and Work Function Characteristics of
      Functional Organic Interfaces.
AB  - The tailoring of organic systems is crucial to further extend the efficiency of
      charge transfer mechanisms and represents a cornerstone for molecular device
      technologies. However, this demands control of electrical properties and
      understanding of the physics behind organic interfaces. Here, a quantitative
      spatial overview of work function characteristics for phthalocyanine
      architectures on Au substrates is provided via kelvin probe microscopy. While
      macroscopic investigations are very informative, the current approach offers a
      nanoscale spatial rendering of electrical characteristics which is not possible
      to attain via conventional techniques. Interface dipole is observed due to the
      formation of charge accumulation layers in thin F16 CuPc, F16 CoPc, and MnPc
      films, displaying work functions of 5.7, 6.1, and 5.0 eV, respectively. The
      imaging and quantification of interface locations with significant surface
      potential and work function response (<0.33 eV for material thickness <1 nm) show
      also a dependency on the crystalline state of the organic systems. The work
      function mapping suggests space-charge carrier regions of about 4 nm at the
      organic interface. This reveals rich spatial electric parameters and ambipolar
      characteristics that may drive electrical performance at device scales, opening a
      realm of possibilities toward the development of functional organic architectures
      and its applications.

PMID- 29450971
TI  - Evaluation of an abutment-level superpower sound processor for bone-anchored
      hearing.
AB  - OBJECTIVES: Performance of an abutment-level superpower sound processor for bone
      anchored hearing, the Ponto 3 SuperPower from Oticon Medical (BCD2), was compared
      to an earlier model from Oticon Medical (BCD1). DESIGN: A comparative study in
      which each patient serves as its own control. SETTING: Tertiary clinic.
      PARTICIPANTS: Eighteen experienced BCD1 users with profound mixed hearing loss.
      MAIN OUTCOME MEASURES: Speech reception thresholds in noise; APHAB and SSQ
      questionnaires. RESULTS: In a group of 18 patients with severe mixed hearing
      loss, the performance of a recently introduced bone conduction device (BCD2) is
      evaluated relative to that of an earlier model (BCD1). Speech reception
      thresholds for the sentence-in-noise test in the speech and noise frontal
      condition are not significantly different (P > .05) for BCD1 and BCD2. Speech
      reception thresholds for frontal speech and three identical noise sources are 1.7
      dB lower for BCD2 than for BCD1 (P < .05). With the APHAB questionnaire, the
      score for background noise is significantly lower (P < .01), that is more
      favourable, for BCD2 than for BCD1 with an effect size of 0.91. The APHAB domain
      scores for ease-of-communication, reverberation and aversiveness of loud sounds
      are not significantly different for both devices (P > .05). Scores for the
      speech, spatial and quality of hearing domains of the SSQ questionnaire are
      significantly higher (P < .01), that is more favourable, for BCD2 than for BCD1
      with effect sizes of 1.22, 0.71 and 1.05, respectively. Scores for the SSQ
      factors "speech understanding," "spatial," "clarity, separation and
      identification" and "listening effort and concentration" were all significantly
      higher (P < .05) for BCD2 than for BCD1, with effect sizes of 1.28, 0.64, 0.98
      and 0.78, respectively. On a proprietary questionnaire, 16 patients indicate a
      preference for BCD2 over BCD1 for conversations in a small group and two patients
      have no preference for either device. In a large group, one patient prefers BCD1,
      six patients have no preference, and eleven patients prefer BCD2. When listening
      to music, all patients prefer BCD2 over BCD1, with a strong preference for BCD2
      for seven patients. When asked for an overall preference, all patients prefer
      BCD2 over BCD1, with nine patients strongly preferring BCD2. CONCLUSIONS: The
      lower speech reception thresholds in noise with BCD2 relative to BCD1 can be
      attributed to the "speech omni" directionality mode of BCD2. The combination of
      an improved directionality for primarily low-level inputs and a higher maximum
      force output, relevant for mid- and high-level inputs, results in a clear
      preference for BCD2 over BCD1.

PMID- 29450972
TI  - How to Construct DNA Hydrogels for Environmental Applications: Advanced Water
      Treatment and Environmental Analysis.
AB  - With high binding affinity, porous structures, safety, green, programmability,
      etc., DNA hydrogels have gained increasing recognition in the environmental
      field, i.e., advanced treatment technology of water and analysis of specific
      pollutants. DNA hydrogels have been demonstrated as versatile potential
      adsorbents, immobilization carriers of bioactive molecules, catalysts, sensors,
      etc. Moreover, altering components or choosing appropriate functional DNA
      optimizes environment-oriented hydrogels. However, the lack of comprehensive
      information hinders the continued optimization. The principle used to fabricate
      the most suitable hydrogels in terms of the requirements is the focus of this
      Review. First, different fabrication strategies are introduced and the ideal
      characteristic for environmental applications is in focus. Subsequently, recent
      environmental applications and the development of diverse DNA hydrogels regarding
      their synthesis mechanism are summarized. Finally, the Review provides an insight
      into the remaining challenging and future perspectives in environmental
      applications.

PMID- 29450973
TI  - Difference between renal and splenic resistive index as a novel criterion in
      Doppler evaluation of renal artery stenosis.
AB  - Detection of renal artery stenosis (RAS) using Doppler is difficult to evaluate,
      particularly under conditions such as bilateral RAS or difficultly accessible
      renal arteries (RA). The objective of the present study was to assess the utility
      of splenic arterial compared to renal flow as an additional parameter in the
      Doppler evaluation of RAS. The difference between the resistive indices (RI)
      determined in renal and splenic parenchymal arteries (DeltaRIK-S ) was evaluated
      in 181 hypertensive subjects without any evidence of RAS. Subsequently 47 RA in
      24 patients with suspected RAS were angiographically assessed. A DeltaRIK-S of
      0.055 (median) was determined in the population without any evidence of RAS
      similar to RA with angiographically excluded stenosis (DeltaRIK-S 0.068). In
      contrast, in angiographic proven RAS, DeltaRIK-S was significantly lower (-0.050;
      P < .005). The assessment of the DeltaRIK-S , proved to be an easily feasible
      parameter, which improves the diagnostic accuracy in the detection of RAS.

PMID- 29450974
TI  - Effect of scaling and root planing on gingival crevicular fluid
      cytokine/chemokine levels in smokers with chronic periodontitis: A systematic
      review.
AB  - In the present study, the impact of scaling and root planing (SRP) on gingival
      crevicular fluid (GCF) cytokine/chemokine levels in smokers with chronic
      periodontitis was assessed. The PICO (population, intervention, comparison,
      outcome) question was: In smokers with chronic periodontitis (population), what
      is the effect of SRP (intervention) in comparison to SRP in non-smokers with
      chronic periodontitis (comparison) on the GCF cytokine/chemokine level (outcome)?
      Indexed databases were searched up to September 2017. Of 4330 titles, nine
      studies reporting the levels of 13 different cytokines/chemokines were included.
      Eight studies had a moderate risk of bias, while one study had a high risk of
      bias. Almost all cytokines/chemokines were pro-inflammatory cytokines. Five
      cytokines/chemokines studied in four clinical studies were decreased in the
      smoker-chronic periodontitis group following SRP. One study observed that the GCF
      levels of interleukin-17 increased, while anti-inflammatory osteoprotegerin was
      reduced in both the SCP and non-smoker-chronic periodontitis groups at follow up.
      However, the majority of cytokines/chemokines did not change in the SCP groups at
      follow up. The current weight of evidence is not sufficient to prove that SRP has
      an impact on GCF cytokine/chemokine profile in smokers with chronic
      periodontitis. Evaluation of wide panels of pro-inflammatory cytokines/chemokines
      related to collagen degradation and alveolar bone destruction in future studies
      are warranted.

PMID- 29450975
TI  - Tropoelastin Implants That Accelerate Wound Repair.
AB  - A novel, pure, synthetic material is presented that promotes the repair of full
      thickness skin wounds. The active component is tropoelastin and leverages its
      ability to promote new blood vessel formation and its cell recruiting properties
      to accelerate wound repair. Key to the technology is the use of a novel heat
      based, stabilized form of human tropoelastin which allows for tunable resorption.
      This implantable material contributes a tailored insert that can be shaped to the
      wound bed, where it hydrates to form a conformable protein hydrogel. Significant
      benefits in the extent of wound healing, dermal repair, and regeneration of
      mature epithelium in healthy pigs are demonstrated. The implant is compatible
      with initial co-treatment with full- and split-thickness skin grafts. The
      implant's superiority to sterile bandaging, commercial hydrogel and dermal
      regeneration template products is shown. On this basis, a new concept for a
      prefabricated tissue repair material for point-of-care treatment of open wounds
      is provided.

PMID- 29450977
TI  - Self-Template-Directed Metal-Organic Frameworks Network and the Derived Honeycomb
      Like Carbon Flakes via Confinement Pyrolysis.
AB  - Metal-organic frameworks (MOFs) have become a research hotspot since they have
      been explored as convenient precursors for preparing various multifunctional
      nanomaterials. However, the preparation of MOF networks with controllable flake
      morphology in large scale is not realized yet. Herein, a self-template strategy
      is developed to prepare MOF networks. In this work, layered double-metal
      hydroxide (LDH) and other layered metal hydroxides are used not only as a
      scaffold but also as a self-sacrificed metal source. After capturing the abundant
      metal cations identically from the LDH by the organic linkers, MOF networks are
      in situ formed. It is interesting that the MOF network-derived carbon materials
      retain the flake morphology and exhibit a unique honeycomb-like macroporous
      structure due to the confined shrinkage of the polyhedral facets. The overall
      properties of the carbon networks are adjustable according to the tailored metal
      compositions in LDH and the derived MOFs, which are desirable for target-oriented
      applications as exemplified by the electrochemical application in
      supercapacitors.

PMID- 29450976
TI  - High Adherence to System-Level Performance Measures for Rheumatoid Arthritis in a
      National Early Arthritis Cohort Over Eight Years.
AB  - OBJECTIVE: To assess adherence to 3 system-level performance measures in a
      national early rheumatoid arthritis (RA) cohort. METHODS: Patients enrolled in
      the Canadian Early Arthritis Cohort (2007-2015) who met 1987 or 2010 American
      College of Rheumatology/European League Against Rheumatism criteria with <1 year
      of symptom duration and >=1 year of followup after enrollment were included.
      Performance measures assessed were the percentage of RA patients seen in yearly
      followup, and the number of gaps between visits of >12 or >14 months, the
      percentage of RA patients treated with a disease-modifying antirheumatic drug
      (DMARD), and days from RA diagnosis to initiation of a DMARD. Results are shown
      stratified by enrollment year to assess for temporal changes in performance.
      RESULTS: A total of 1,763 early RA patients were included (mean age 54 years, 73%
      female, and 82% white). At enrollment, mean +/- SD disease duration was 6 +/- 3
      months, and Disease Activity Score in 28 joints was 5.1 +/- 1.5. Over 8 years,
      the proportion of patients seen in annual followup declined from 100% to 91%.
      Over followup, 42% of patients had 0 gaps in care of >12 months, and 64% had 0
      gaps >14 months. The percentage of DMARD-treated early RA patients was and
      remained high (95-87%), and the percentage receiving DMARDs within 14 days of
      diagnosis was 75%. Median time-to-DMARD therapy was 1 day, indicating DMARDs were
      initiated at diagnosis (90th percentile 93 days). CONCLUSION: There was evidence
      of high adherence to system-level performance measures in this early RA cohort
      following a protocol. Small declines in performance were noted with increasing
      length of patient followup. Our findings are useful for performance measure
      benchmarking.

PMID- 29450978
TI  - Prognostic comparison of the 7th and 8th editions of the American Joint Committee
      on Cancer staging system for intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: Several important changes were made to the 8th edition of the
      American Joint Committee on Cancer (AJCC) tumor staging system for intrahepatic
      cholangiocarcinoma (ICC). We assessed the prognostic impact of this new tumor
      staging system compared to the 7th edition. METHODS: A retrospective single
      institution study was performed with 626 patients who underwent R0 resection for
      ICC over 20-year period. RESULTS: Anatomical resection and concurrent bile duct
      resection were performed in 571 (91.2%) and 62 (9.9%) patients, respectively.
      Cumulative tumor recurrence and patient survival rates were 40.6% and 73.3% at 1
      year; 66.7% and 43.8% at 3 years; 73.6% and 30.4% at 5 years; and 74.4% and 20.3%
      at 10 years, respectively. Independent prognostic factors for tumor recurrence
      and patient survival were multiple tumors, carbohydrate antigen 19-9 >200 U/ml,
      tumor size >5 cm, direct invasion to extrahepatic structure, and lymph node
      metastasis. For tumor-node-metastasis stages in the 7th versus the 8th editions,
      concordance index was 0.615 and 0.625 for tumor recurrence and 0.626 and 0.628
      for patient survival, respectively. CONCLUSIONS: The 8th edition of the AJCC
      staging system appears to provide high prognostic contrast for T stage
      categories, except for T3. However, overall prognostic performance of the 8th
      edition was not markedly improved over the 7th edition.

PMID- 29450979
TI  - Guidance on home blood pressure monitoring: A statement of the HOPE Asia Network.
AB  - Hypertension is an important modifiable cardiovascular risk factor and a leading
      cause of death throughout Asia. Effective prevention and control of hypertension
      in the region remain a significant challenge despite the availability of several
      regional and international guidelines. Out-of-office measurement of blood
      pressure (BP), including home BP monitoring (HBPM), is an important hypertension
      management tool. Home BP is better than office BP for predicting cardiovascular
      risk and HBPM should be considered for all patients with office BP >= 130/85 mm
      Hg. It is important that HBPM is undertaken using a validated device and patients
      are educated about how to perform HBPM correctly. During antihypertensive
      therapy, monitoring of home BP control and variability is essential, especially
      in the morning. This is because HBPM can facilitate the choice of individualized
      optimal therapy. The evidence and practice points in this document are based on
      the Hypertension Cardiovascular Outcome Prevention and Evidence (HOPE) Asia
      Network expert panel consensus recommendations for HBPM in Asia.

PMID- 29450981
TI  - Nurr1 promotes neurogenesis of dopaminergic neuron and represses inflammatory
      factors in the transwell coculture system of neural stem cells and microglia.
AB  - INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell
      replacement therapy for Parkinson's disease (PD). However, a majority of the
      transplanted NSCs differentiated into glial cells, thereby limiting the clinical
      application. Previous studies indicated that chronic neuroinflammation plays a
      vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the
      developing potential of therapies for PD by targeting the inflammatory processes.
      Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been
      referred to play a pivotal role in both the differentiation of dopaminergic
      neurons in embryonic stages and the maintenance of the dopaminergic phenotype
      throughout life. AIM: This study investigated the effect of Nurr1 on
      neuroinflammation and differentiation of NSCs cocultured with primary microglia
      in the transwell coculture system. RESULTS: The results showed that Nurr1 exerted
      anti-inflammatory effects and promoted the differentiation of NSCs into
      dopaminergic neurons. CONCLUSIONS: The results suggested that Nurr1 protects
      dopaminergic neurons from neuroinflammation insults by limiting the production of
      neurotoxic mediators by microglia and maintain the survival of transplanted NSCs.
      These phenomena provided a new theoretical and experimental foundation for the
      transplantation of Nurr1-overexpressed NSCs as a potential treatment of PD.

PMID- 29450980
TI  - Prediction of enteric methane production, yield, and intensity in dairy cattle
      using an intercontinental database.
AB  - Enteric methane (CH4 ) production from cattle contributes to global greenhouse
      gas emissions. Measurement of enteric CH4 is complex, expensive, and impractical
      at large scales; therefore, models are commonly used to predict CH4 production.
      However, building robust prediction models requires extensive data from animals
      under different management systems worldwide. The objectives of this study were
      to (1) collate a global database of enteric CH4 production from individual
      lactating dairy cattle; (2) determine the availability of key variables for
      predicting enteric CH4 production (g/day per cow), yield [g/kg dry matter intake
      (DMI)], and intensity (g/kg energy corrected milk) and their respective
      relationships; (3) develop intercontinental and regional models and cross
      validate their performance; and (4) assess the trade-off between availability of
      on-farm inputs and CH4 prediction accuracy. The intercontinental database covered
      Europe (EU), the United States (US), and Australia (AU). A sequential approach
      was taken by incrementally adding key variables to develop models with increasing
      complexity. Methane emissions were predicted by fitting linear mixed models.
      Within model categories, an intercontinental model with the most available
      independent variables performed best with root mean square prediction error
      (RMSPE) as a percentage of mean observed value of 16.6%, 14.7%, and 19.8% for
      intercontinental, EU, and United States regions, respectively. Less complex
      models requiring only DMI had predictive ability comparable to complex models.
      Enteric CH4 production, yield, and intensity prediction models developed on an
      intercontinental basis had similar performance across regions, however,
      intercepts and slopes were different with implications for prediction. Revised
      CH4 emission conversion factors for specific regions are required to improve CH4
      production estimates in national inventories. In conclusion, information on DMI
      is required for good prediction, and other factors such as dietary neutral
      detergent fiber (NDF) concentration, improve the prediction. For enteric CH4
      yield and intensity prediction, information on milk yield and composition is
      required for better estimation.

PMID- 29450983
TI  - Association between encounter frequency and time to blood pressure control among
      patients with newly diagnosed hypertension: a retrospective cohort study.
AB  - This retrospective cohort study of 95 957 patients from a large integrated
      healthcare organization was conducted to examine whether the frequency and
      intervals between outpatient encounters were associated with achieving blood
      pressure (BP) control. Patients were followed up until they were censored or
      achieved BP control up to 1 year. Additionally, this study examined the time to
      BP control. On average, follow-up was significantly longer in patients with
      uncontrolled BP at 292.9 days compared with 232.2 days in those with BP control.
      The controlled BP group had significantly more encounters on average compared
      with the uncontrolled BP group (4.1 vs 3.1, standardized difference 0.33). As the
      number of days increased between encounters from the 1 to < 14 days, there was a
      consistently lower likelihood of achieving BP control. Encounter intervals of
      >=180 days were associated with the lowest likelihood of achieving BP control.
      These findings suggest that there may be an optimal number of encounters to
      benefit patients with hypertension.

PMID- 29450982
TI  - Application of off-line two-dimensional high-performance countercurrent
      chromatography on the chloroform-soluble extract of Cuscuta auralis seeds.
AB  - In this study, the chloroform-soluble extract of Cuscuta auralis was separated
      successfully using off-line two-dimensional high-performance countercurrent
      chromatography, yielding a gamma-pyrone, two alkaloids, a flavonoid, and four
      lignans. The first-dimensional countercurrent separation using a methylene
      chloride/methanol/water (11:6:5, v/v/v) system yielded three subfractions
      (fractions I-III). The second-dimensional countercurrent separations, conducted
      on fractions I-III using n-hexane/ethyl acetate/methanol/water/acetic acid
      (5:5:5:5:0, 3:7:3:7:0, and 1:9:1:9:0.01, v/v/v/v/v) systems, gave maltol (1), (-)
      (13S)-cuscutamine (2), (+)-(13R)-cuscutamine (3), (+)-pinoresinol (4), (+)
      epipinoresinol (5), kaempferol (6), piperitol (7), and (9R)-hydroxy-d-sesamin
      (8). To the best of our knowledge, maltol was identified for the first time in
      Cuscuta species. Furthermore, this report details the first full assignment of
      spectroscopic data of two cuscutamine epimers, (-)-(13S)-cuscutamine and (+)
      (13R)-cuscutamine.

PMID- 29450984
TI  - Computational studies on horseshoe shape pocket of human orexin receptor type 2
      and boat conformation of suvorexant by molecular dynamics simulations.
AB  - The FDA approved drug suvorexant binds to the horseshoe shape pocket of OX2 R
      with the boat conformation. The horseshoe shape pocket plays an important role on
      the biological activity of OX2 R in the cell membrane. To study the binding
      mechanism between the horseshoe shape pocket of OX2 R and boat conformation of
      suvorexant, the crystal structures of wild type and N324A mutant of OX2 R in
      complex with antagonist suvorexant are chosen to perform molecular dynamics (MD)
      simulations, QM/MM, and MMGBSA calculations. By comparison with the wild type of
      OX2 R, the results show the 1,2,3-triazole and p-toluamide groups of suvorexant
      are changed in the N324A mutant of OX2 R during 200 ns MD simulations. The QM/MM
      and weak interaction analysis are employed to calculate the non-covalent bonds
      interaction between suvorexant and key residues in the wild type and N324A mutant
      of OX2 R. The MMGBSA calculations indicate the entropy energy is an important
      influence factor for suvorexant affinity in the distorted horseshoe shape pocket
      of OX2 R. Our results not only show the horseshoe shape pocket of OX2 R is the
      necessary conformation for the binding of antagonist suvorexant, but also give
      the important sites and structural features for antagonist design of OX2 R.

PMID- 29450986
TI  - Upcoming events of interest.

PMID- 29450987
TI  - Habit-tic cough: Presentation and outcome with simple reassurance.

PMID- 29450985
TI  - Effect of secondary electron generation on dose enhancement in Lipiodol with and
      without a flattening filter.
AB  - PURPOSE: Lipiodol, which was used in transcatheter arterial chemoembolization
      before liver stereotactic body radiation therapy (SBRT), remains in SBRT.
      Previous we reported the dose enhancement in Lipiodol using 10 MV (10*) FFF beam.
      In this study, we compared the dose enhancement in Lipiodol and evaluated the
      probability of electron generation (PEG) for the dose enhancement using
      flattening filter (FF) and flattening filter free (FFF) beams. METHODS: FF and
      FFF for 6 MV (6*) and 10* beams were delivered by TrueBeam. The dose enhancement
      factor (DEF), energy spectrum, and PEG was calculated using Monte Carlo (MC) code
      BEAMnrc and heavy ion transport code system (PHITS). RESULTS: DEFs for FF and FFF
      6* beams were 7.0% and 17.0% at the center of Lipiodol (depth, 6.5 cm). DEFs for
      FF and FFF 10* beams were 8.2% and 10.5% at the center of Lipiodol. Spectral
      analysis revealed that the FFF beams contained more low-energy (0-0.3 MeV)
      electrons than the FF beams, and the FF beams contained more high-energy (>0.3
      MeV) electrons than the FFF beams in Lipiodol. The difference between FFF and FF
      beam DEFs was larger for 6* than for 10*. This occurred because the 10* beams
      contained more high-energy electrons. The PEGs for photoelectric absorption and
      Compton scattering for the FFF beams were higher than those for the FF beams. The
      PEG for the photoelectric absorption was higher than that for Compton scattering.
      CONCLUSIONS: FFF beam contained more low-energy photons and it contributed to the
      dose enhancement. Energy spectra and PEGs are useful for analyzing the mechanisms
      of dose enhancement.

PMID- 29450988
TI  - Salso-bromo-iodine thermal water: a nonpharmacological alternative treatment for
      postnasal drip-related cough in children with upper respiratory tract infections.
AB  - Postnasal drip (PND)-related cough is a very common symptom in patients with
      upper respiratory tract infections (URTIs). At present, there is not a standard
      treatment for postnasal drip and postnasal drip-related cough. The aim of this
      pilot study was to evaluate the efficacy of a specific salso-bromo-iodine thermal
      water containing hyaluronic acid and grapefruit seed extract (SBI-H-GSE)
      comparing it with a normal saline solution in children with URTIs who refer PND
      related symptoms. The study was randomized, single-blind, and controlled. Study
      group (75 children) was treated with SBI-H-GSE and control group (65 children)
      was treated with a normal saline solution; both compounds were administered by
      nasal nebulization with Rinowash nasal douche twice/day for 10 days a month for 3
      consecutive months. Parent Cough-Specific Quality of Life questionnaire (PC-QOL)
      average score, the prevalence of symptoms and signs related to post-nasal drip,
      nasal mucociliary transport time (NMTT), duration and number of URTI episodes,
      antibiotic usage and days of absence from school were evaluated at baseline and
      after treatment. SBI-H-GSE therapy shows better and statistically significant
      trend after treatment when compared to control group for PC-QOL average score
      (p=0.011), NMTT (p=0.047), symptoms and signs related to post-nasal drip (all
      p<0.005, except for the cobblestone appearance of the mucosa), duration (in days)
      with URTI symptoms (p=0.023) and a usage of antibiotic therapy (p=0.011). The
      current randomized-controlled pilot study demonstrated that SBI-H-GSE solution
      was effective in the treatment of children with URTIs who refer PND-related
      symptoms.

PMID- 29450989
TI  - Implementation of hepatitis B birth dose vaccination - worldwide, 2016.

PMID- 29450990
TI  - Splicing Site Recognition by Synergy of Three Domains in Splicing Factor RBM10.
AB  - Splicing factor RBM10 and its close homologues RBM5 and RBM6 govern the splicing
      of oncogenes such as Fas, NUMB, and Bcl-X. The molecular architecture of these
      proteins includes zinc fingers (ZnFs) and RNA recognition motifs (RRMs). Three of
      these domains in RBM10 that constitute the RNA binding part of this splicing
      factor were found to individually bind RNAs with micromolar affinities. It was
      thus of interest to further investigate the structural basis of the well
      documented high-affinity RNA recognition by RMB10. Here, we investigated RNA
      binding by combinations of two or three of these domains and discovered that a
      polypeptide containing RRM1, ZnF1, and RRM2 connected by their natural linkers
      recognizes a specific sequence of the Fas exon 6 mRNA with an affinity of 20 nM.
      Nuclear magnetic resonance structures of the RBM10 domains RRM1 and ZnF1 and the
      natural V354del isoform of RRM2 further confirmed that the interactions with RNA
      are driven by canonical RNA recognition elements. The well-known high-fidelity
      RNA splice site recognition by RBM10, and probably by RBM5 and RBM6, can thus be
      largely rationalized by a cooperative binding action of RRM and ZnF domains.

PMID- 29450991
TI  - Mass Spectrometry-Based Fast Photochemical Oxidation of Proteins (FPOP) for
      Higher Order Structure Characterization.
AB  - Assessment of protein structure and interaction is crucial for understanding
      protein structure/function relationships. Compared to high-resolution structural
      tools, including X-ray crystallography, nuclear magnetic resonance (NMR), and
      cryo-EM, and traditional low-resolution methods, such as circular dichroism, UV
      vis, and florescence spectroscopy, mass spectrometry (MS)-based protein
      footprinting affords medium-to-high resolution (i.e., regional and residue
      specific insights) by taking advantage of proteomics methods focused on the
      primary structure. The methodology relies on "painting" the reactive and solvent
      exposed amino acid residues with chemical tags and using the pattern of
      modifications as footprints from analysis by bottom-up MS-based proteomics to
      deduce protein higher order structures. The outcome can refer to proteins in
      solution or even in cells and is complementary to those of X-ray crystallography
      and NMR. It is particularly useful in mapping protein-ligand interfaces and
      conformational changes resulting from ligand binding, mutation, and aggregation.
      Fast photochemical oxidation of proteins (FPOP), in its original conception, is a
      type of hydroxyl-radical-based protein footprinting that utilizes a pulsed KrF
      laser (248 nm) to trigger hydrolysis of hydrogen peroxide to produce solution
      hydroxyl radicals, which subsequently modify the protein in situ. The platform is
      expanding to adopt other reactive species including carbenes. The reactivity of
      the probe depends on the intrinsic reactivity of the radical with the residue
      side chain and the solvent accessibility of the residue as a function of the
      tertiary/quaternary structures. By introducing an appropriate scavenger to
      compete with hydroxyl radical self-quenching, the lifetime of the primary
      radicals is remarkably shortened to approximately microsecond. Thus, the sampling
      time scale of FPOP is much faster than hydrogen-deuterium exchange and other
      covalent labeling methods relying on nonradical reactions. The short footprinting
      time scale of FPOP offers two major advantages for protein structure elucidation:
      (1) it allows the protein to be interrogated in its native or near-native state
      with minimum structural perturbation; (2) it exhibits high sensitivity toward
      alterations in protein higher order structures because its sampling time is short
      with respect to protein conformational changes and dynamic motion. In addition,
      the covalent and irreversible oxidation by the hydroxyl radical provides more
      flexibility in the downstream proteomics workflow and MS analysis, permitting
      high spatial resolution with residue-specific information. Since its invention in
      2005 by Hambly and Gross, FPOP has developed from proof-of-concept to a valuable
      biophysical tool for interrogating protein structure. In this Account, we
      summarize the principles and experimental design of FPOP that enable its fast
      labeling and describe the current and unique capabilities of the technique in
      protein higher order structure elucidation. Application examples include
      characterization of amyloid beta self-assembly, protein-ligand interactions with
      a special emphasis on epitope mapping for protein therapeutics (e.g., antibody,
      Fab, and adnectin), protein folding detailed to residue-specific folding
      kinetics, and protein flexibility/dynamics. Additionally, the utility of FPOP
      based oxidative footprinting should grow with our continuing developments of
      novel reagents (e.g., sulfate radical anion, carbene diradical, and
      trifluoromethyl radical). These reactive reagents are compatible with the current
      FPOP platform and offer different reactivity and selectivity toward various types
      of amino acid residues, providing complementary insights into protein higher
      order structures for soluble proteins and ultimately for membrane-bound proteins.

PMID- 29450992
TI  - Assessment of Fragmentation Strategies for Large Proteins Using the Multilayer
      Molecules-in-Molecules Approach.
AB  - We present a rigorous evaluation of the potential for the multilayer Molecules-in
      Molecules (MIM) fragmentation method to be applied to large biomolecules. Density
      functional total energies of a test set of 8 peptides, sizes ranging from 107 to
      721 atoms, were evaluated with MIM and compared to unfragmented energies to help
      develop a protocol for the treatment of large proteins. Fragmentation schemes
      involving subsystems of 4 to 5 covalently bonded fragments (tetramer or pentamer
      schemes) were tested with a single level of theory (MIM1) and produced errors on
      the order of 100 kcal/mol due to the relatively small size of the subsystems and
      the neglect of nonbonded interactions. Supplementing the two schemes with
      nonbonded dimer subsystems, formed from fragments within a specified cutoff
      distance (3.0 A), nearly cut the MIM1 errors in half, leading us to employ these
      new schemes as starting points in multilayer calculations. When employing a DFT
      low level with a substantially smaller basis set (MIM2), the dimer-supplemented
      schemes produce errors below our target accuracy of 2 kcal/mol in the majority of
      cases. However, for the larger test systems, such as the 45 residue slice of a
      human protein kinase with over 10,000 basis functions in the high level, the low
      level calculation over the full molecule becomes the bottleneck for MIM2
      calculations. To overcome any associated limitations, we explored, for the first
      time, 3-layer MIM methods (MIM3) with a distance-based medium level of
      fragmentation and dispersion-corrected semiempirical methods (e.g., PM6-D3) as
      the low level. A modestly sized cutoff distance in the medium level (3.0-3.5 A),
      leading to subsystems of 30-50 atoms treated at the medium and low levels of
      theory, was able to match the low errors of the MIM2 calculations. These results
      allow us to develop a general prescription for 3-layer calculations wherein a
      much cheaper low level can be used, while fragment sizes in the high layer stay
      modest, allowing the MIM method to be applied to very large proteins in the
      future.

PMID- 29450993
TI  - Near Infrared Photoimmunotherapy with Combined Exposure of External and
      Interstitial Light Sources.
AB  - Near infrared photoimmunotherapy (NIR-PIT) is a new target-cell-specific cancer
      treatment that induces highly selective necrotic/immunogenic cell death after
      systemic administration of a photoabsorber antibody conjugate and subsequent NIR
      light exposure. However, the depth of NIR light penetration in tissue
      (approximately 2 cm) with external light sources limits the therapeutic effects
      of NIR-PIT. Interstitial light exposure using cylindrical diffusing optical
      fibers can overcome this limitation. The purpose in this study was to compare
      three NIR light delivery methods for treating tumors with NIR-PIT using a NIR
      laser system at an identical light energy; external exposure alone, interstitial
      exposure alone, and the combination. Panitumumab conjugated with the
      photoabsorber IRDye-700DX (pan-IR700) was intravenously administered to mice with
      A431-luc xenografts which are epithelial growth factor receptor (EGFR) positive.
      One and 2 days later, NIR light was administered to the tumors using one of three
      methods. Interstitial exposure alone and in combination with external sources
      showed the greatest decrease in bioluminescence signal intensity. Additionally,
      the combination of external and interstitial NIR light exposure showed
      significantly greater tumor size reduction and prolonged survival after NIR-PIT
      compared to external exposure alone. This result suggested that the combination
      of external and interstitial NIR light exposure was more effective than
      externally applied light alone. Although external exposure is the least invasive
      means of delivering light, the combination of external and interstitial exposures
      produces superior therapeutic efficacy in tumors greater than 2 cm in depth from
      the tissue surface.

PMID- 29450994
TI  - Simpterpenoid A, a Meroterpenoid with a Highly Functionalized Cyclohexadiene
      Moiety Featuring gem-Propane-1,2-dione and Methylformate Groups, from the
      Mangrove-Derived Penicillium simplicissimum MA-332.
AB  - Simpterpenoid A (1), an unprecedented meroterpenoid possessing a highly
      functionalized cyclohexadiene moiety (ring C) featuring gem-propane-1,2-dione and
      methylformate groups, was characterized from mangrove-derived Penicillium
      simplicissimum MA-332. Due to the highly oxygenated and functionalized ring C and
      lack of some key correlations, the unambiguous assignment of the planar structure
      and steric configuration was solved by X-ray crystallographic analysis. Compound
      1 exhibited inhibitory activity against influenza neuraminidase in nanomolar
      quantities.

PMID- 29450995
TI  - N-Acyl-glutarimides: Resonance and Proton Affinities of Rotationally-Inverted
      Twisted Amides Relevant to N-C(O) Cross-Coupling.
AB  - Resonance energies and proton affinities of N-acyl-glutarimides, compared with
      related twisted acyclic amides of relevance to N-C(O) cross-coupling, are
      reported. The data demonstrate that amidic resonance in N-acyl-glutarimides
      practically disappears (ER < 2.8 kcal/mol), while, intriguingly, these amides
      favor O-protonation despite significant twist. In some cases, N-acyl-glutarimides
      undergo intramolecular N- to O-acyl migration, indicative of high capacity as
      acylating reagents. The understanding provided for the high reactivity of N-acyl
      glutarimides should facilitate the development of a broadly general N-C(O) amide
      activation platform.

PMID- 29450996
TI  - Copper-Catalyzed C(sp)-C(sp3) Coupling of Terminal Alkynes with Alkylsilyl
      Peroxides via a Radical Mechanism.
AB  - A copper-catalyzed C(sp)-C(sp3) coupling reaction between terminal alkynes and
      alkylsilyl peroxides is reported. In the presence of a copper catalyst and 4
      dimethylaminopyridine, the reaction smoothly affords a variety of internal
      alkynes by coupling alkylsilyl peroxides and terminal alkynes. Mechanistic
      studies suggest that the reaction proceeds via a radical mechanism, whereby the
      alkyl radicals are generated from the alkylsilyl peroxides. The present
      transformation represents a rare example of a radical-mediated C(sp)-C(sp3)
      coupling reaction of terminal alkynes.

PMID- 29450997
TI  - 2-Aminoquinazolin-4(3H)-one as an Organocatalyst for the Synthesis of Tertiary
      Amines.
AB  - The potential of 2-aminoquinazolin-4(3H)-one as an organocatalyst for the
      activation of aldehydes via noncovalent interaction for the synthesis of tertiary
      amines using formic acid as a reducing agent is reported for the first time. The
      developed protocol demonstrated a dilated substrate scope for aromatic and
      aliphatic amines with aromatic and aliphatic aldehydes. Furthermore, the current
      method was also fruitful for the derivatization of ciprofloxacin and its
      derivative in good to excellent yields.

PMID- 29450998
TI  - Stereoselective Synthesis of the Benzodihydropentalene Core of the Fijiolides.
AB  - An efficient stereoselective synthesis of the enantiomer of the
      benzodihydropentalene core of fijiolides A and B has been achieved. The
      asymmetric conjugate addition of styrylboronic acid to an indenone produced the
      first stereocenter. Ring C was installed by ring-closing metathesis of a cis
      disubstituted indanone. Regioselective epoxide opening by NaSePh and subsequent
      oxidative elimination produced an allylic alcohol. The final introduction of the
      cyclopentadiene was possible by elimination of an in situ formed triflate.

PMID- 29450999
TI  - alpha-Functionalization of 2-Vinylpyridines via a Chiral Phosphine Catalyzed
      Enantioselective Cross Rauhut-Currier Reaction.
AB  - Herein, 2-vinylpyridines as a new type of electron-poor system for the asymmetric
      cross Rauhut-Currier reaction are reported. 2-Vinylpyridines are chemo- and
      enantioselectively activated by a newly designed chiral phosphine catalyst. The
      new reaction provides a powerful synthetic tool for accessing structurally
      diverse, highly valued chiral pyridine building blocks in good yields and with
      high enantioselectivities. Preliminary mechanistic studies reveal that two NH
      protons in the catalyst are critical for the synergistic activation of the
      substrates and governing the stereoselectivity of this reaction.

PMID- 29451000
TI  - Novel automated immune turbidimetric assay for routine urinary cystatin-C
      determinations.
AB  - AIM: There is no commercially available urinary cystatin-C (u-CYSC) test in the
      market. Therefore, we optimized and validated an automated immune turbidimetric
      test for u-CYSC measurements and investigated u-CYSC concentrations in acute and
      chronic diseases which might lead to renal tubular disorders. MATERIALS &
      METHODS: A particle-enhanced immune turbidimetric assay was adapted and validated
      on a Cobas 8000/c502 analyzer. Urine samples of different patient groups were
      also analyzed. RESULTS: Our method showed excellent analytical performance. U
      CYSC/u-creatinine (u-CREAT) was higher in sepsis-related acute kidney injury
      group (p < 0.001) compared with controls and to patients with chronic
      hypertension and Type 2 diabetes. CONCLUSION: We validated a fast, sensitive,
      fully automated u-CYSC assay which is ideal for routine use and might be a
      potential complementary laboratory test to evaluate renal tubular function.

PMID- 29451001
TI  - Parallel artificial liquid membrane extraction of psychoactive analytes: a novel
      approach in therapeutic drug monitoring.
AB  - AIM: Liquid-liquid extraction is widely used in therapeutic drug monitoring of
      antipsychotics, but difficulties in automation of the technique can result in
      long operational time. In this paper, parallel artificial liquid membrane
      extraction was used for extraction of serotonin- and serotonin-norepinephrine
      reuptake inhibitors from human plasma, and an approach to automate the technique
      was investigated. RESULTS: Eight model analytes were extracted from 125 MUl human
      plasma with recoveries in the range 72-111% (relative standard deviation [RSD]
      <=12.8%). A semiautomated pipettor was successfully utilized in the procedure,
      reducing the manual handling time. Real patient samples were analyzed with
      satisfying accuracy. CONCLUSION: A semiautomated extraction of serotonin-and
      serotonin-norepinephrine reuptake inhibitors by parallel artificial liquid
      membrane extraction extraction was successfully performed.

PMID- 29451002
TI  - Healing stories: An expressive-narrative intervention for strengthening
      resilience and survival skills in school-aged child victims of war and political
      violence in the Gaza Strip.
AB  - Within a preventive framework, we outline a school-based intervention aimed at
      strengthening skills of survival and psychological functioning in children who
      have experienced war and political violence in the Gaza Strip. In accordance with
      a socio-ecological perspective on wellbeing and resilience, the pilot study aimed
      at evaluating the outcomes of a psychosocial narrative school-based intervention
      with a group of school-aged children in the aftermath of war. The intervention
      was oriented at empowering positive emotions, life satisfaction, and optimism in
      children as protective factors in preventing posttraumatic reactions after war.
      Findings showed the efficacy of the intervention in favoring life satisfaction in
      different ecological domains. Children in the intervention group showed greater
      appreciation for friends, school, family, themselves, and their living
      environment. At the end of the activity, children were increased the level of
      positive emotions, but negative feelings were stronger than before the narrative
      intervention. Clinical implications and future direction or community work are,
      then, discussed.

PMID- 29451003
TI  - Escherichia coli isolates from femoral bone marrow of broilers exhibit diverse
      pheno- and genotypic characteristics that do not correlate with macroscopic
      lesions of bacterial chondronecrosis with osteomyelitis.
AB  - The pheno- and genotypic relatedness among Escherichia coli isolates from
      broilers with and without macroscopic lesions of the femoral head were
      investigated. In total, 219 isolates obtained from the bone marrow were
      characterized by serotyping, antimicrobial resistance (AMR) profiles,
      phylogenetic grouping, detection of virulence-associated genes (VAGs) and pulsed
      field gel electrophoresis (PFGE). Serotyping revealed that 48.4% of the isolates
      were assigned to one of the three serotypes (O78:K80: 21.0%, O2:K1: 18.7%, O1:K1:
      8.7%). Substantial phenotypic variation was also noticed in AMR testing as most
      of the birds harboured E. coli isolates with different AMR profiles, which is of
      high clinical relevance. The majority of isolates could be classified into
      phylogenetic groups D (54.3%) and B2 (25.6%), followed by A (11.4%) and B1
      (8.7%). Virulotyping showed that the highest number of isolates contained genes
      iucD (86.8%) and iss (84.9%), whereas papC (16.0%) and astA (12.3%) were present
      in least number of isolates. PFGE resulted in 58 different profiles from 200
      typeable isolates. No correlation was found between specific serotypes, AMR
      profiles, phylogenetic groups, PFGE types or VAG profiles of E. coli and the
      occurrence of bacterial chondronecrosis with osteomyelitis, contradicting the
      hypothesis of a specific bacterial pheno- or genotype being involved in the
      disease.

PMID- 29451004
TI  - Simulating localised cellular inflammation and substrate properties in a strain
      energy density based bone remodelling algorithm for use in modelling trauma.
AB  - Bone responds to mechanical stimulus and a range of pre-existing finite element
      models have been suggested to reproduce the internal physiological structure of
      bone. Inflammation effects are not included in these models, yet inflammation is
      a key component of bone repair in trauma. Therefore, a model is proposed and
      tested here that extends these methods to include parameters that could be
      considered to represent the behaviour of bone remodelling when influenced by
      inflammation. The proposed model regulates remodelling based on findings from
      recent studies into the nature of heterotopic ossification, the formation of
      heterotopic bone, which have revealed information about the nature of bone after
      high levels of trauma. These parameters include consideration of the distance
      from the zone of trauma, the density of mesenchymal stem cells, and substrate
      stiffness as a trigger for cells becoming osteogenic. The method is tested on a
      two-dimensional plate model and shows that the new extended algorithm can produce
      a range of structures depending on inputs that could be used in the future to
      replicate physiological scenarios.

PMID- 29451007
TI  - Fractures in the Pediatric Emergency Department: Are We Considering Abuse?
AB  - Approximately one fourths of infant fractures are due to abuse. Recognition of
      abuse is important to avoid further morbidity/mortality. There is limited
      knowledge regarding how frequently pediatric emergency department clinicians
      consider abuse in infants with fractures. Our primary objective was to estimate
      the percentage of infants with fractures for whom abuse was considered, and to
      examine characteristics associated with abuse consideration. We performed a
      retrospective review of infants <1 year of age presenting to a pediatric
      emergency department. Our primary outcome variable was consideration of abuse.
      Our secondary outcome measures were identification of predictor variables
      associated with consideration of abuse. We identified 509 infants meeting study
      criteria. Pediatric emergency physicians considered abuse in approximately two
      thirds of infants with fractures. Consideration was more likely to occur in
      younger infants, in the presence of no history or unwitnessed injury mechanism,
      when evaluated by male physicians, and emergency department encounters from 12 am
      to 6 am.

PMID- 29451006
TI  - Different Indexes of Glycemic Variability as Identifiers of Patients with Risk of
      Hypoglycemia in Type 2 Diabetes Mellitus.
AB  - INTRODUCTION: Recent publications frequently introduce new indexes to measure
      glycemic variability (GV), quality of glycemic control, or glycemic risk;
      however, there is a lack of evidence supporting the use of one particular
      parameter, especially in clinical practice. METHODS: A cohort of type 2 diabetes
      mellitus (T2DM) patients in ambulatory care were followed using continuous
      glucose monitoring sensors (CGM). Mean glucose (MG), standard deviation,
      coefficient of variation (CV), interquartile range, CONGA1, 2, and 4, MAGE, M
      value, J index, high blood glucose index, and low blood glucose index (LBGI) were
      estimated. Hypoglycemia incidence (<54 mg/dl) was calculated. Area under the
      curve (AUC) was determined for different indexes as identifiers of patients with
      risk of hypoglycemia (IRH). Optimal cutoff thresholds were determined from
      analysis of the receiver operating characteristic curves. RESULTS: CGM data for
      657 days from 140 T2DM patients (4.69 average days per patient) were analyzed.
      Hypoglycemia was present in 50 patients with 144 hypoglycemic events in total
      (incidence rate of 0.22 events per patient/day). In the multivariate analysis,
      both CV (OR 1.20, 95% CI 1.12-1.28, P < .001) and LBGI (OR 4.83, 95% CI 2.41
      9.71, P < .001) were shown to have a statistically significant association with
      hypoglycemia. The highest AUC were for CV (0.84; 95% CI 0.77-0.91) and LBGI
      (0.95; 95% CI 0.92-0.98). The optimal cutoff threshold for CV as IRH was 34%, and
      3.4 for LBGI. CONCLUSION: This analysis shows that CV can be recommended as the
      preferred parameter of GV to be used in clinical practice for T2DM patients. LBGI
      is the preferred IRH between glycemic risk indexes.

PMID- 29451005
TI  - HIV Infection and risk of postpartum infection, complications and mortality in
      rural Uganda.
AB  - HIV infection may increase risk of postpartum infection and infection-related
      mortality. We hypothesized that postpartum infection incidence and attributable
      mortality in Mbarara, Uganda would be higher in HIV-infected than HIV-uninfected
      women. We performed a prospective cohort study of 4231 women presenting to a
      regional referral hospital in 2015 for delivery or postpartum care. All febrile
      or hypothermic women, and a subset of randomly selected normothermic women were
      followed during hospitalization and with 6-week postpartum phone interviews. The
      primary outcome was in-hospital postpartum infection. Secondary outcomes included
      in-hospital complications (mortality, re-operation, intensive care unit transfer,
      need for imaging or blood transfusion) and 6-week mortality. We performed
      multivariable regression analyses to estimate adjusted differences in each
      outcome by HIV serostatus. Mean age was 25.2 years and 481 participants (11%)
      were HIV-infected. Median CD4+ count was 487 (IQR 325, 696) cells/mm3, and 90% of
      HIV-infected women (193/215 selected for in-depth survey) were on antiretroviral
      therapy. Overall, 5% (205/4231) of women developed fever or hypothermia.
      Cumulative in-hospital postpartum infection incidence was 2.0% and did not differ
      by HIV status (aOR 1.4, 95% CI 0.6-3.3, P = 0.49). However, more HIV-infected
      women developed postpartum complications (4.4% vs. 1.2%, P = 0.001). In-hospital
      mortality was rare (2/1768, 0.1%), and remained so at 6 weeks (4/1526, 0.3%),
      without differences by HIV serostatus (P = 1.0 and 0.31, respectively). For women
      in rural Uganda with high rates of antiretroviral therapy coverage, HIV infection
      did not predict postpartum infection or mortality, but was associated with
      increased risk of postpartum complications.

PMID- 29451008
TI  - Utilization of Patient Navigators in an Urban Academic Pediatric Primary Care
      Practice.
AB  - Navigating health care systems can be a challenge for families. A retrospective
      descriptive cohort analysis was conducted assessing referrals to patient
      navigators (PNs) in one urban academic pediatric primary care practice. PNs
      tracked referral processes and a subset of PN referrals was assessed for markers
      of successful referrals. The most common reasons for referral were assistance
      overcoming barriers to care (46%), developmental concerns (38%), and
      adherence/care coordination concerns (14%). Significant predictors of referral
      were younger age, medical complexity, public insurance, male sex, and higher
      rates of no-show to visits in primary or subspecialist care. The majority of
      referrals were resolved. The referrals for process-oriented needs were
      significantly more successful than those for other concerns. PNs were more
      effective for discrete process tasks than for those that required behavior change
      by patients or families. Future directions include analysis of cost effectiveness
      of the PN program and analysis of parent and primary care provider experience.

PMID- 29451009
TI  - Risk factors influencing severity of attention deficit hyperactivity disorder in
      a sample of preparatory school students in Cairo.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most
      common childhood psychiatric disorders. Severity of symptoms is associated with
      more behavioral problems, poor academic performance, and persistence of symptoms
      into adulthood. METHODS: To examine the clinical and social correlates that may
      be identified as risk factors associated with ADHD severity in a sample of
      adolescent ADHD school students. A total of 925 students were recruited from two
      public and two private schools from eastern Cairo. They were interviewed using
      Conners-Wells Adolescent Self-Report-short version (CASS-S); students scoring
      more than 65 were further interviewed with Kiddie Schedule for Affective
      Disorders and Schizophrenia-present and lifetime version (K-SADS-PL) to confirm
      the diagnosis, then Conners-Wells Adolescent Self-Report-long version (CASS-L) to
      assess severity and Wechsler Intelligence Scale for Children (WISC) to ascertain
      intellectual ability. RESULTS: About 10.3% of cases were severe, 5.7% were
      moderate, and 83.9% were mild. Severity was significantly associated with female
      gender, psychiatric comorbidity, family problems, conduct symptoms, and poor
      anger management. Diagnostic and Statistical Manual of Mental Disorders (4th ed.)
      ( DSM-IV) hyperactive-impulsive type was the only predictive factor of ADHD
      severity. CONCLUSIONS: The diagnosis of hyperactive-impulsive subtype may predict
      the severity of ADHD symptoms.

PMID- 29451010
TI  - Assessment of Mycoplasma gallisepticum vaccine efficacy in a co-infection
      challenge model with QX-like infectious bronchitis virus.
AB  - Mycoplasma gallisepticum (MG) is the primary cause of chronic respiratory disease
      in poultry. We investigated the protective efficacy of the live-attenuated ts-11
      and 6/85 MG vaccines against a local MG strain and, in order to enhance signs and
      mimic a typical field situation, we co-infected birds with a virulent strain of
      QX-like infectious bronchitis virus (IBV). Both vaccines showed similar ability
      to protect infected chickens from clinical signs, although ts-11 performed
      slightly better. Despite the lower protection against clinical disease, 6/85
      vaccinated birds had significantly (P <= 0.05) lower tracheal lesion scores and
      mucosal thickness at day 28 post-vaccination (7 days post-challenge [dpc] with
      MG, 2 dpc IBV) and day 31 post-vaccination (10 dpc MG challenge, 5 dpc IBV)
      compared to ts-11 vaccinated birds, but these difference was not significant at
      day 33 (12 dpc MG, 7 dpc IBV). Pathogen infection and replication was assessed by
      qPCR, and the 6/85 vaccine produced a more significant (P <= 0.05) reduction in
      MG replication in the lungs, kidneys and livers but enhanced late replication in
      bursae and caecal tonsils. In contrast, the ts-11 vaccine had a more pronounced
      reductive effect on replication in tracheas, air sacs, bursae and heart at days
      28 and 31, yet increased replication in lungs. Interestingly, both vaccines
      provided non-specific protection against IBV challenge. The co-challenge model
      provided useful data on vaccine efficacy, especially on days 31 and 33, and
      tracheas, lungs, air sacs, kidneys, liver and caecal tonsils were the best organs
      to assess.

PMID- 29451011
TI  - LC-MSn small-molecule drug analysis in human serum: could adducts have good
      prospects for therapeutic applications?

PMID- 29451012
TI  - 4-dehydroxyepisarcovagine A, a new steroidal alkaloid from Sarcococca pruniformis
      Lindl.
AB  - A new steroidal alkaloid, 4-dehydroxyepisarcovagine A (1), along with seven known
      alkaloids, sarcovagine D (2), sarcovagenine C (3), epoxysarcovagenine D (4),
      Pachysamine L (5), Pachysamine E (6), sarcovagine A (7) and sarcovagine B (8),
      was isolated from the roots and stems of Sarcococca pruniformis Lindl. The
      structure of compound 1 was elucidated by means of spectroscopic analysis.

PMID- 29451013
TI  - Pradimicin-IRD from Amycolatopsis sp. IRD-009 and its antimicrobial and cytotoxic
      activities.
AB  - A new polycyclic antibiotic, pradimicin-IRD, was isolated from actinobacteria
      Amycolatopsis sp. IRD-009 recovered from soil of Brazilian rainforest undergoing
      restoration area. This molecule is the major compound produced in solid culture
      media. The new compound was detected by a focused method of precursor ion (high
      performance liquid chromatography coupled to tandem mass spectrometer) developed
      previously to identify unusual aminoglycosyl sugar moieties. The compound was
      isolated and its structure was, therefore, elucidated by high-resolution mass
      spectrometry, and 1D and 2D nuclear magnetic resonance experiments. Pradimicin
      IRD displayed potential antimicrobial activity against Streptococcus agalactiae
      (MIC 3.1 MUg/mL), Pseudomonas aeruginosa (MIC 3.1 MUg/mL) and Staphylococcus
      aureus (MIC 3.1 MUg/mL), and also cytotoxicity against tumour and non-tumour cell
      lines with IC50 values ranging from 0.8 MUM in HCT-116 colon carcinoma cells to
      2.7 MUM in MM 200 melanoma cells. Particularly, these biological properties are
      described for the first time for this chemical class.

PMID- 29451014
TI  - The MusIC method: a fast and quasi-optimal solution to the muscle forces
      estimation problem.
AB  - The present paper aims at presenting a fast and quasi-optimal method of muscle
      forces estimation: the MusIC method. It consists in interpolating a first
      estimation in a database generated offline thanks to a classical optimization
      problem, and then correcting it to respect the motion dynamics. Three different
      cost functions - two polynomial criteria and a min/max criterion - were tested on
      a planar musculoskeletal model. The MusIC method provides a computation frequency
      approximately 10 times higher compared to a classical optimization problem with a
      relative mean error of 4% on cost function evaluation.

PMID- 29451015
TI  - Chemical constituents from the rhizomes of Polygonatum sibiricum Red. and anti
      inflammatory activity in RAW264.7 macrophage cells.
AB  - Chemical investigation of the rhizomes of Polygonatum sibiricum Red. led to the
      identification of 27 constituents. Among them, a total of 16 compounds were
      obtained from Polygonatum for the first time, in which, 3 and 4 were also firstly
      isolated as natural products. Anti-inflammatory activity studies on 13 isolated
      compounds showed that beta-carboline constituents, especially compounds 1 and 2,
      significantly inhibited the expression of NO, TNF-alpha, IL-6 and IL-1beta in
      lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells. Moreover, western
      blotting analysis demonstrated that compound 1 significantly inhibited the
      expression of COX-2, iNOS and the activation of NF-kappaB, suggesting that beta
      carboline structures may play an important role in inhibition of NF-kappaB
      signaling pathway, which thereby inhibits the production of inflammatory factors.
      The present research may not only help further elucidation of the anti
      inflammatory mechanism of P. sibiricum Red., but also provide the potential
      bioactive molecules for inflammatory diseases research.

PMID- 29451016
TI  - Evaluation of a New Noninvasive Glucose Monitoring Device by Means of
      Standardized Meal Experiments.
AB  - BACKGROUND:: Frequent blood glucose readings are the most cumbersome aspect of
      diabetes treatment for many patients. The noninvasive TensorTip Combo Glucometer
      (CoG) component employs dedicated mathematical algorithms to analyze the
      collected signal and to predict tissue glucose at the fingertip. This study
      presents the performance of the CoG (the invasive and the noninvasive components)
      during a standardized meal experiment. METHODS:: Each of the 36 participants (18
      females and males each, age: 49 +/- 18 years, 14 healthy subjects, 6 type 1 and
      16 type 2 patients) received a device for conducting calibration at home.
      Thereafter, they ingested a standardized meal. Blood glucose was assessed from
      capillary blood samples by means of the (non)invasive device, YSI Stat 2300 plus,
      Contour Next at time points -30, 0, 15, 30, 45, 60, 75, 90, 120, 150, and 180
      minutes. Statistical analysis was performed by consensus error grid (CEG) and
      calculation of mean absolute relative difference (MARD) in comparison to YSI.
      RESULTS:: For the noninvasive (NI) CoG technology, 100% of the data pairs were
      found in CEG zones A (96.6%) and B (3.4%); 100% were seen in zone A for the
      invasive component and Contour Next. MARD was calculated to be 4.2% for Contour
      Next, 9.2% for the invasive component, and 14.4% for the NI component.
      CONCLUSIONS:: After appropriate individual calibration of the NI technology, both
      the NI and the invasive CoG components reliably tracked tissue and blood glucose
      values, respectively. This may enable patients with diabetes to monitor their
      glucose levels frequently, reliably, and most of all pain-free.

PMID- 29451017
TI  - Assessing Quality Control Strategies for HbA1c Measurements From a Patient Risk
      Perspective.
AB  - BACKGROUND: Current laboratory risk management principles emphasize the
      importance of assessing laboratory quality control (QC) practices in terms of the
      risk of patient harm. Limited practical guidance or examples on how to do this
      are available. METHODS: The patient risk model described in a published
      laboratory risk management guideline was combined with a recently reported
      approach to computing the predicted probability of patient harm to produce a risk
      management index (RMI) that compares the predicted probability of patient harm
      for a QC strategy to the acceptable probability of patient harm based on the
      expected severity of harm caused by an erroneously reported patient result.
      RESULTS: Measurement procedure capability and quality control performance for two
      instruments measuring HbA1c in a laboratory were assessed by computing the RMI
      for each instrument individually and for the laboratory as a whole. CONCLUSIONS:
      This assessment provides a concrete example of how laboratory QC practices can be
      directly correlated to the risk of patient harm from erroneously reported patient
      results.

PMID- 29451018
TI  - Incorporating dried blood spot LC-MS/MS analysis for clinical development of a
      novel oncolytic agent.
AB  - AIM: Design and execution of a dried blood spot (DBS-LC-MS/MS) assay for
      pharmacokinetic analyses in oncology patients. RESULTS & DISCUSSION: The
      methodology was validated to collect and store DBS samples from multiple clinical
      sites, and analyze blood with diverse hematocrit ranges (25-55) to match the
      potential patient population. Bridging data comparing DBS and plasma showed high
      degree of concordance with DBS:plasma ratios of 0.81, demonstrating no
      preferential uptake or association with cellular components of the blood.
      Pharmacokinetic analysis supporting clinical development was performed using 20
      MUl of blood collected as DBS. Incurred sample reanalysis showed high
      correlation. CONCLUSION: Successful validation of a DBS method and implementation
      in the clinic enabled pharmacokinetic analysis during the clinical development of
      a novel oncolytic agent in oncology patients.

PMID- 29451019
TI  - Antimicrobial substances from the rare actinomycete Nonomuraea rhodomycinica NR4
      ASC07T.
AB  - Nonomuraea rhodomycinica NR4-ASC07T is a rare actinomycete isolated from soil in
      Sirindhorn peat swamp forest. The crude extract of its culture broth exhibited
      antimicrobial and anticancer against diverse human pathogens and cancer cells.
      The chemical investigation of the crude extract led to the isolation of two new
      metabolites named nonomuric acid (1) and 3-hydroxy deoxydaunorubicinol aglycone
      (2), along with two known bioactive compounds [epsilon-rhodomycinone (3) and 7
      deoxy-13-dihydrocarminomycinone (4)]. Compounds 1 and 3 showed antimalarial
      activity with the half maximal inhibitory concentration (IC50) of 8.00 and 8.88
      MUg mL-1, respectively. Compound 4 inhibited growth of Mycobacterium tuberculosis
      and Bacillus cereus at the minimum inhibitory concentrations of 50.0 and 12.50
      MUg mL-1, respectively. Every compound exhibited cytotoxicity against cancer
      cells tested at IC50 >= 6.34 MUg mL-1. These finding are the first report of
      bioactive metabolites produced by strain NR4-ASC07T, suggesting that rare
      actinomycetes are yet promising sources for novel drug discovery.

PMID- 29451020
TI  - The brigatinib experience: a new generation of therapy for ALK-positive non-small
      cell lung cancer.
AB  - Lung cancer remains the leading cause of cancer deaths in the world with 1.69
      million deaths in 2015. A total of 85% of lung cancer cases are non-small-cell
      lung cancers (NSCLCs). Driver mutations associated with anaplastic lymphoma
      kinase (ALK) have been identified in a variety of malignancies, including NSCLC.
      An ALK inhibitor (crizotinib, ceritinib and alectinib) is the preferred
      therapeutic approach to those advanced ALK fusion variant-positive NSCLC
      patients. Brigatinib, a next-generation ALK inhibitor, shows promising activity
      in ALK-rearranged NSCLC that have previously received crizotinib with response
      rates in ALTA ranging from 42-50%, intracranial response 42-67% and median
      progression-free survival 9.2-12.9 months. Randomized Phase III trial, ALTA-1 L
      is investigating brigatinib in ALK inhibitor-naive patients.

PMID- 29451021
TI  - The UVA/Padova Type 1 Diabetes Simulator Goes From Single Meal to Single Day.
AB  - BACKGROUND: A new version of the UVA/Padova Type 1 Diabetes (T1D) Simulator is
      presented which provides a more realistic testing scenario. The upgrades to the
      previous simulator, which was accepted by the Food and Drug Administration in
      2013, are described. METHOD: Intraday variability of insulin sensitivity (SI) has
      been modeled, based on clinical T1D data, accounting for both intra- and
      intersubject variability of daily SI. Thus, time-varying distributions of both
      subject's basal insulin infusion and insulin-to-carbohydrate ratio were
      calculated and made available to the user. A model of "dawn" phenomenon based on
      clinical T1D data has been also included. Moreover, the model of subcutaneous
      insulin delivery has been updated with a recently developed model of commercially
      available fast-acting insulin analogs. Models of both intradermal and inhaled
      insulin pharmacokinetics have been included. Finally, new models of error
      affecting continuous glucose monitoring and self-monitoring of blood glucose
      devices have been added. RESULTS: One hundred in silico adults, adolescent, and
      children have been generated according to the above modifications. The new
      simulator reproduces the intraday glucose variability observed in clinical data,
      also describing the nocturnal glucose increase, and the simulated insulin
      profiles reflect real life data. CONCLUSIONS: The new modifications introduced in
      the T1D simulator allow to extend its domain of validity from "single-meal" to
      "single-day" scenarios, thus enabling a more realistic framework for in silico
      testing of advanced diabetes technologies including glucose sensors, new insulin
      molecules and artificial pancreas.

PMID- 29451022
TI  - Breast tomosynthesis for the clarification of mammographic BI-RADS 3 lesions can
      decrease follow-up examinations and enables immediate cancer diagnosis.
AB  - Background The limited sensitivity of mammography in case of a high breast
      density often produces unclear or false-positive findings, so-called BI-RADS 3
      lesions, which have to be followed up to prove benignity. Digital breast
      tomosynthesis (DBT) was developed to reduce such summation effects. Purpose To
      evaluate the influence of an additional DBT on the management of mammographic BI
      RADS 3 findings and whether DBT can decrease the time to definitive diagnosis or
      not. Material and Methods We analyzed 87 patients with a mammographic non
      calcified BI-RADS 3 lesion who underwent an additional DBT of the affected
      breast. A follow-up two-dimensional (2D) examination or a histological result of
      the lesion had to be available. The images were analyzed especially for the BI
      RADS category and incremental diagnostic accuracy. Moreover, the inter-reader
      reliability and the radiation dose were evaluated. Results The BI-RADS category
      has been changed by the addition of DBT: 57.1% were assessed as BI-RADS 1 or 2,
      4.6% as BI-RADS 4, and only 38.3% remained as BI-RADS 3. The intraclass
      correlation coefficient for the three readers showed a good agreement for inter
      reader reliability. No false-negative examination was found in the follow-ups.
      Nine lesions were biopsied (seven benign, two malignant). Both malignant lesions
      were suspicious in the DBT (BI-RADS 4). A significant higher glandular dose was
      necessary for the DBT. Conclusion DBT has the potential to reduce the recall-rate
      of BI-RADS 3 lesions and to find and diagnose malignant lesions earlier than 2D
      mammography alone.

PMID- 29451023
TI  - Mammographic screening attendance among immigrant and minority women: a
      systematic review and meta-analysis.
AB  - Background Groups of immigrant and minority women are more often diagnosed with
      advanced stage breast cancer than other women. Mammographic screening aims to
      reduce mortality from breast cancer through early detection in asymptomatic
      women. Purpose To compare mammographic screening attendance among immigrant and
      minority women to that of other women. Material and Methods A literature search
      of PubMed, Embase, Google Scholar, and Cochrane identified 1369 papers published
      between January 1995 and March 2016. In the review, we included 33 studies
      investigating mammographic screening attendance among immigrant and/or minority
      women. In a meta-analysis, we included 19 of the studies that compared attendance
      among immigrant and/or minority women with that among other women, using a random
      effects model. Results The review included studies from Europe, North America,
      and Oceania, with 42,666,093 observations of opportunities for mammographic
      screening. Attendance was generally lower among immigrant and minority women
      compared to other women (46.2% vs. 55.0%; odds ratio = 0.64, 95% confidence
      interval = 0.56-0.73; P < 0.05, I2 = 99.9%). Non-Western immigrants had lower
      attendance rates than other immigrants. Conclusion Immigrant and minority women
      had lower mammographic screening attendance than other women, which could
      potentially put them at increased risk for more advanced breast cancer. This
      review emphasizes the importance of continued efforts to engage with the
      preventative health needs of diverse populations in attempts to achieve equality
      in access to, and use of, care.

PMID- 29451024
TI  - Network pharmacology-based screening of the active ingredients and potential
      targets of the genus of Pithecellobium marthae (Britton & Killip) Niezgoda & Nevl
      for application to Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated
      with synaptic dysfunction, pathological accumulation of beta-amyloid (Abeta), and
      neuronal loss. Given the prevalence of AD and the lack of effective long-term
      therapies, there is a pressing need to discover viable leads that can be
      developed into clinically approved drugs with disease-modifying effects. The
      analysis of current reported literatures confirms the importance of the plants of
      Pithecellobium genus as candidate against AD. Hence, it is necessary to identify
      selective anti-dementia agents from this genus. To explore potential compounds
      with marked effect on AD in Pithecellobium genus, a compound database based on
      the methods of network pharmacology prediction was established in this paper by
      constructing the compound-disease target network. The result showed that the most
      effective compound in the plants of this genus might be (7'R,8'R)-7'-methoxyl
      strebluslignanol, and the most potential target might be Macrophage colony
      stimulating factor 1 receptor.

PMID- 29451025
TI  - Person-oriented research ethics: integrating relational and everyday ethics in
      research.
AB  - Research ethics is often understood by researchers primarily through the
      regulatory framework reflected in the research ethics review process. This
      regulatory understanding does not encompass the range of ethical considerations
      in research, notably those associated with the relational and everyday aspects of
      human subject research. In order to support researchers in their effort to adopt
      a broader lens, this article presents a "person-oriented research ethics"
      approach. Five practical guideposts of person-oriented research ethics are
      identified, as follows: (1) respect for holistic personhood; (2) acknowledgement
      of lived world; (3) individualization; (4) focus on researcher-participant
      relationships; and (5) empowerment in decision-making. These guideposts are
      defined and illustrated with respect to different aspects of the research process
      (e.g., research design, recruitment, data collection). The person-oriented
      research ethics approach provides a toolkit to individual researchers, research
      groups, and research institutions in both biomedical and social science research
      wishing to expand their commitment to ethics in research.

PMID- 29451026
TI  - The TiM system: developing a novel telehealth service to improve access to
      specialist care in motor neurone disease using user-centered design.
AB  - OBJECTIVES: Attendance at a specialist multidisciplinary motor neurone disease
      (MND) clinic is associated with improved survival and may also improve quality of
      life and reduce hospital admissions. However, patients struggle to travel to
      clinic and may experience difficulties between clinic visits that may not be
      addressed in a timely manner. We wanted to explore how we could improve access to
      specialist MND care. METHODS: We adopted an iterative, user-centered co-design
      approach, collaborating with those with experience of providing and receiving MND
      care including patients, carers, clinicians, and technology developers. We
      explored the unmet needs of those living with MND, how they might be met through
      service redesign and through the use of digital technologies. We developed a new
      digital solution and performed initial testing with potential users including
      clinicians, patients, and carers. RESULTS: We used these findings to develop a
      telehealth system (TiM) using an Android app into which patients and carers
      answer a series of questions about their condition on a weekly basis. The
      questions aim to capture all the physical, emotional, and social difficulties
      associated with MND. This information is immediately uploaded to the internet for
      review by the MND team. The data undergoes analysis in order to alert clinicians
      to any changes in a patient or carer's condition. CONCLUSIONS: We describe the
      benefits of developing a novel digitally enabled service underpinned by
      participatory design. Future trials must evaluate the feasibility and
      acceptability of the TiM system within a clinical environment.

PMID- 29451027
TI  - A case of late-onset OCD developing PLS and FTD.
AB  - We describe a 64-year-old woman, suffering from late-onset obsessive-compulsive
      disorder (OCD) from the age of 57, who developed dysarthria and dysphagia,
      spastic diplegic, and proximal muscles weakness. Needle electromyography showed
      no active denervation. Neuropsychological evaluation showed intact cognitive
      functioning. We diagnosed upper motor neuron disease (MND), with no known genetic
      correlates. Brain magnetic resonance (MRI) detected bilateral hippocampal atrophy
      with sclerosis of right hippocampus. 18F-FDG positron emission tomography (PET)
      showed moderate right temporal cortex thinning. Six months later, motor and
      behavioral symptoms worsened. Neuropsychological examination revealed long-term
      memory deficit and executive dysfunction. MRI and PET evidenced severe worsening
      of atrophy in temporal and frontal lobes. Four years later a definitive diagnosis
      of primary lateral sclerosis (PLS) and FTD was made. To our knowledge, this is
      the first report of PLS and FTD with OCD at onset.

PMID- 29451028
TI  - L'ethique du silence : le conflit d'interets explique-t-il le silence des
      employes?
AB  - Le silence des employes constitue une menace importante pour la reussite des
      organisations. Dans le present article, les auteurs avancent que le silence
      derive du conflit d'interets (CdI) structurel entre les employes et leur
      employeur. Cet argument repose sur la these egalement defendue dans l'article
      selon laquelle les leaders, qu'ils l'acceptent ou non, dependent de leurs
      employes pour obtenir de l'information fiable sur le travail effectue, car ceux
      ci connaissent intimement ce qu'ils font. La parole des employes devient donc une
      necessite organisationnelle. C'est egalement une realisation morale, car elle
      oblige l'individu a risquer ses interets personnels au profit de ceux de
      l'organisation. Les leaders doivent prendre des mesures pour attenuer les CdI et
      inciter les employes a s'exprimer. Le present article leur fournit plusieurs
      strategies en ce sens.

PMID- 29451029
TI  - Screening of ionic liquids for extraction of flavonoids from heather.
AB  - Room temperature ionic liquids are novel solvents with the specific properties
      that makes them of interest for application for extraction for a wide range of
      compounds. In this work extraction efficiency of flavonoids from heather flowers
      using ionic liquids based on imidazolium cation were evaluated and compared with
      organic solvents. It was found that the anion of ionic liquid significantly
      influence the extraction yields. Flavonoid content as well as antioxidant
      activity based on radical scavenging on 1,1-diphenul-2-pirylhydrazyl radicals and
      cupric reducing antioxidant capacity increased in the order: [Bmim]PF6 <
      [Bmim]BF4 < [Bmim]Cl. The obtained extraction yield using [Bmim]Cl were higher
      than reported for 60% ethanol and ethyl acetate under similar conditions, thus,
      may be helpful for better utilization of heather flowers as the potential
      pharmaceutical and nutraceutical ingredients.

PMID- 29451030
TI  - Health Promotion for These Times.

PMID- 29451032
TI  - Corrigendum.

PMID- 29451031
TI  - Condom Use Efficacy and Sexual Communication Skills Among African American
      College Women.
AB  - Despite condom use being the most protective measure against the transmission of
      human immunodeficiency virus (HIV), little is known about the intermediary
      relationships between condom negotiation, assertive sexual communication, and
      condom use efficacy. The purpose of the current study was to examine the
      relationships between these constructs within the context of an HIV prevention
      intervention. We examined two samples of African American college women
      participating in two HIV prevention interventions, one of which was based on
      social learning theory ( N = 214). Data collected at intervention posttest and 3
      month follow-up were analyzed. Findings revealed that condom use efficacy at
      posttest fully mediated the relationship between intervention effect and
      assertive sexual communication at 3-month follow-up. In addition, condom use
      efficacy at posttest fully mediated the relationship between intervention effect
      and condom negotiation at 3-month follow-up. Implications of the importance of
      experiential learning, in combination with behavior observance, on the
      maintenance of condom protective behaviors are discussed. Findings have the
      potential to inform clinic and community-based HIV prevention interventions
      conducted among African American women.

PMID- 29451033
TI  - Control release of mitochondria-targeted antioxidant by injectable self
      assembling peptide hydrogel ameliorated persistent mitochondrial dysfunction and
      inflammation after acute kidney injury.
AB  - Persistent mitochondrial injury occurs after acute kidney injury (AKI) and
      mitochondria-targeted antioxidant Mito-2,2,6,6-tetramethylpiperidine-N-oxyl
      (TEMPO) (MT) has shown benefits for AKI, but its efficiency is limited by short
      half-life and side effect in vivo. Self-assembling peptide (SAP) hydrogel is a
      robust platform for drug delivery. This study aims to develop an SAP-based
      carrier to slow release MT for enhancing its long-term therapeutic potency on
      AKI. The KLD with aspartic acid (KLDD) was designed. The microstructure and in
      vitro release of MT was assayed. The protective role of MT-loaded SAP (SAP-MT)
      hydrogel on renal mitochondrial injury, tubular apoptosis, and inflammation was
      evaluated in mice at five days after ischemia-reperfusion injury (IRI). Our
      results showed that KLDD could self-assemble into cross-linked nanofiber hydrogel
      and it had lower release rate than free MT and KLD hydrogel. Compared to IRI and
      free MT mice, SAP-MT mice exerted reduced renal mitochondria-produced ROS (mtROS)
      and improved mitochondrial biogenesis and architecture. Consequently, SAP-MT mice
      showed less renal tubular cell apoptosis, kidney injury marker kidney injury
      molecule-1 (Kim-1) expression, lower level of pro-inflammatory factors
      expression, and macrophages infiltration than those of IRI and free MT mice. This
      study suggested that SAP-MT ameliorated IRI due to its extended mitochondrial
      protection role than free MT and thus improved the long-term outcomes of AKI.

PMID- 29451034
TI  - Cytochrome P450 in the central nervous system as a therapeutic target in
      neurodegenerative diseases.
AB  - Cytochromes P450 (CYPs) constitute a family of enzymes that can be found in the
      endoplasmic reticulum (ER), mitochondria or the cell surface of the cells. CYPs
      are characterized by carrying out the oxidation of organic compounds and they are
      mainly recognized as mediators of the biotransformation of xenobiotics to polar
      hydrophilic metabolites that can be eliminated from the organism. However, these
      enzymes play a key role in many other physiological processes, being involved in
      diverse indispensable metabolic pathways since they metabolize many endogenous
      substrates. Various CYP isoforms are expressed in the brain, and it is believed
      that this could be in part due to the particular function of brain CYPs. In the
      brain, CYPs are involved in the cholesterol turnover, the biosynthesis of
      dopamine, serotonin, morphine, hormones, and protective lipid mediators
      (epoxyeicosatrienoic acids), in addition to their already recognized role in
      xenobiotics detoxification and psychotropic drug metabolism. Increasing evidence
      suggests that this group of enzymes is fundamental for the normal functioning and
      maintenance of brain homeostasis. This review is focused on highlighting the
      importance of CYP-mediated endogenous metabolism in the central nervous system
      (CNS) and its relationship with recent findings regarding CYP involvement in
      neurodegenerative diseases. Some therapeutic approaches focused on CYP regulation
      are also discussed.

PMID- 29451036
TI  - Pharmaceutical-grade chondroitin sulfate in the management of knee
      osteoarthritis.
AB  - INTRODUCTION: Chondroitin Sulfate (CS) is a drug which is available as
      pharmaceutical-grade and nutriceutical-grade products, with important variations
      in preparation, composition, purity and therapeutic effects. Previous studies
      using pharmaceutical-grade CS suggested that the compound improves pain and
      function and delays structural progression in knee osteoarthritis (OA), whereas
      discrepant results were observed when lower grade preparations were investigated.
      Areas covered: The recently published chondroitin versus celecoxib versus Placebo
      Trial (CONCEPT) assessed the symptomatic effect of pharmaceutical-grade CS 800
      mg/day in symptomatic knee OA. Expert opinion: This prospective, randomized, 6
      month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day) -
      controlled trial involved 604 patients aged above 50 years with primary knee OA.
      This study showed that CS is superior to placebo and similar to celecoxib in
      reducing pain and improving function in Kellgren-Lawrence grade 1-3 patients
      supporting the role of pharmaceutical-grade CS as a potential first-line
      treatment for the management of patients with mild to moderate knee OA.

PMID- 29451035
TI  - Revisiting the physiological effects of methylene blue as a treatment of cyanide
      intoxication.
AB  - BACKGROUND: Although methylene blue (MB) had long been proposed to counteract the
      effects of cyanide (CN) intoxication, research on its mechanisms of action and
      efficacy has been abandoned for decades. Recent studies on the benefits of MB in
      post-anoxic injuries have prompted us to reexamine the relevance of this
      historical observation. METHODS: Our study was performed in adult male Sprague
      Dawley rats and on HEK293T epithelial cells. First, the effects and toxicity of
      MB (0-80 mg/kg) on circulation and metabolism were established in four urethane
      anesthetized rats. Then nine rats received a lethal infusion of a solution of KCN
      (0.75 mg/kg/min) and were treated by either saline or MB, at 20 mg/kg, a dose
      that we found to be innocuous in rat and to correspond to a dose of about 4 mg/kg
      in humans. MB was also administered 5 min after the end of a sub-lethal exposure
      to CN in a separate group of 10 rats. In addition, ATP/ADP ratio, ROS production,
      mitochondrial membrane potential (Deltapsim) and cellular O2 consumption rate
      (OCR) were determined in HEK293T cells exposed to toxic levels of CN (200 uM for
      10 min) before and after applying a solution containing MB (1-100 uM for 10 min).
      RESULTS: Methylene blue was found to be innocuous up to 50 mg/kg. KCN infusion
      (0.75 mg/kg/min) killed all animals within 7-8 min. MB (20 mg/kg) administered at
      the same time restored blood pressure, cardiac contractility and limited O2
      deficit, allowing all the animals to survive, without any significant
      methemoglobinemia. When administered 5 min after a non-lethal CN intoxication, MB
      sped up the recovery of lactate and O2 deficit. Finally, MB was able to decrease
      the production of ROS and restore the ATP/ADP ratio, Deltapsim as well as OCR of
      epithelial cells intoxicated by CN. CONCLUSIONS: The present observations should
      make us consider the potential interest of MB in the treatment of CN
      intoxication. The mechanisms of the antidotal properties of MB cannot be
      accounted for by the creation of a cyanomethemoglobinemia, rather its protective
      effects appears to be related to the unique properties of this redox dye, which,
      depending on the dose, could directly oppose some of the consequences of the
      metabolic depression produced by CN at the cellular level.

PMID- 29451037
TI  - Esophageal hiatal hernia: risk, diagnosis and management.
AB  - INTRODUCTION: Esophageal hiatal hernia involves abnormal abdominal entry into
      thoracic cavity. It is classified based on orientation between esophageal
      junction and diaphragm. Sliding hiatal hernia (Type-I) comprises the most
      frequent category, emanating from right crus of diaphragm. Type-II esophageal
      hernia engages both left and right muscular crura. Type-III and IV additionally
      include the left crus. Age and increased body mass index are key risk factors,
      and congenital skeletal aberrations trigger pathogenesis through intestinal
      malrotations. Familiar manifestations include gastric reflux, nausea, bloating,
      chest and epigastric discomfort, pharyngeal and esophageal expulsion and
      dysphagia. Weight loss and colorectal bleeding are severe symptoms. Areas
      covered: This review summarizes updated evidence of pathophysiology, risk
      factors, diagnosis and management of hiatal hernias. Laparoscopy and
      oesophagectomy procedures have been discussed as surgical procedures. Expert
      commentary: Endoscopy identifies untreatable gastric reflux; radiology is better
      for pre-operative assessments; manometry measures esophageal peristalsis, and CT
      scanning detects gastric volvulus and associated organ ruptures. Gastric reflux
      disease is mitigated using antacids and proton pump and histamine-2-receptor
      blockers. Severe abdominal penetration into chest cavity demands surgical
      approaches. Hence, esophagectomy has chances of post-operative morbidity, while
      minimally invasive laparoscopy entails fewer postoperative difficulties and
      better visualization of hernia and related vascular damages.

PMID- 29451038
TI  - Effect of finasteride particle size reduction on its pharmacokinetic, tissue
      distribution and cellular permeation.
AB  - Finasteride (FSD), a specific competitive inhibitor of the steroid type-II 5alpha
      reductase enzyme, is used in treatment of benign prostate hyperplasia (BPH) and
      male pattern baldness. The drug is of limited solubility that affect its
      dissolution and bioavailability. The aim was to study the effect of FSD particle
      size reduction on the pharmacokinetic, tissue distribution and cellular
      permeation. An optimized drug micro- and nano-particles were developed,
      characterized, administered to group of rats, and systemic pharmacokinetic and
      tissue distribution within target and not-target organs were determined using
      near-infrared (NIR) spectroscopy technique. Moreover, the cellular permeation of
      the prepared formulations through normal prostate epithelial cells was assessed
      and compared to pure FSD. The developed micro- and nano-particles were of 930 and
      645 nm, respectively. Plasma maximum drug levels (Cmax) and overall exposure
      (AUC) of both formulations were not significantly higher than unformulated drug.
      However, micronized FSD achieved significant higher concentration within the
      target tissue (prostate) within the current study compared to pure drug and nano
      sized formulation as well. Yet, this is explained by the higher sequestration
      ability of spleen tissue to the nano-sized formula compared to micro-sized FSD.
      At the cellular level, permeation of nano-sized FSD through prostate epithelial
      cells was superior to the unformulated FSD as well as the micro-sized drug
      formulation. FSD particle size reduction significantly influences its cellular
      permeation and to a lesser extend affect its systemic pharmacokinetics and tissue
      distribution after oral administration.

PMID- 29451039
TI  - Tulip Finger.

PMID- 29451041
TI  - Mental health status of unmarried youth living in single parent families: a case
      study from India.
AB  - BACKGROUND: In South Asian countries like India, family system lays a strong
      foundation in societies and therefore, the context and consequences of single
      parent family structures are markedly different from that of the West. In these
      societies single parenthood is mainly an outcome of untimely death of any one of
      the parents. AIMS: This study tried to examine the influence of parents' survival
      status on the mental health of youth in India. METHODS: "Youth in India:
      situation and Needs (2006-2007)" survey data was used in the present study. We
      compared two groups of unmarried young population aged 15-24 y (n = 28 637): one
      having both parents alive and another having only one parent alive. Bivariate and
      multivariate techniques were applied to analyze the data. RESULTS: Results
      revealed that around 11% of the unmarried youth belonged to single parent
      families. Findings underscored a significant association between parent's
      survival and mental health of youth; respondents from single parent families were
      more likely to report metal health problems Moreover, effects of parents'
      survival were significant on females' mental health rather than males'.
      CONCLUSION: Policies must focus on reducing stress of young people growing up in
      single parent families through enhanced educational and employment opportunities.

PMID- 29451040
TI  - Pulmonary delivery of influenza vaccine formulations in cotton rats: site of
      deposition plays a minor role in the protective efficacy against clinical isolate
      of H1N1pdm virus.
AB  - Administration of influenza vaccines to the lungs could be an attractive
      alternative to conventional parenteral administration. In this study, we
      investigated the deposition site of pulmonary delivered liquid and powder
      influenza vaccine formulations and its relation to their immunogenicity and
      protective efficacy. In vivo deposition studies in cotton rats revealed that, the
      powder formulation was mainly deposited in the trachea ( ~ 65%) whereas the
      liquid was homogenously distributed throughout the lungs ( ~ 96%). In addition,
      only 60% of the antigen in the powder formulation was deposited in the
      respiratory tract with respect to the liquid formulation. Immunogenicity studies
      showed that pulmonary delivered liquid and powder influenza formulations induced
      robust systemic and mucosal immune responses (significantly higher by liquids
      than by powders). When challenged with a clinical isolate of homologous H1N1pdm
      virus, all animals pulmonary administered with placebo had detectable virus in
      their lungs one day post challenge. In contrast, none of the vaccinated animals
      had detectable lung virus titers, except for two out of eight animals from the
      powder immunized group. Also, pulmonary vaccinated animals showed no or little
      signs of infection like increase in breathing frequency or weight loss upon
      challenge as compared to animals from the negative control group. In conclusion,
      immune responses induced by liquid formulation were significantly higher than
      responses induced by powder formulation, but the overall protective efficacy of
      both formulations was comparable. Thus, pulmonary immunization is capable of
      inducing protective immunity and the site of antigen deposition seems to be of
      minor relevance in inducing protection.

PMID- 29451042
TI  - Dual LABA/LAMA bronchodilators in chronic obstructive pulmonary disease: why,
      when, and how.

PMID- 29451043
TI  - Murepavadin: a new antibiotic class in the pipeline.
AB  - INTRODUCTION: With the increase in multi-drug resistant P. aeruginosa,
      antimicrobials with a novel mechanism of action are needed that can target these
      infections. Areas covered: Intravenous murepavadin is in Phase 3 development for
      the treatment of HABP/VABP due to P. aeruginosa. This paper summarizes the
      available information on the discovery, the in vitro activity, pharmacokinetic
      and pharmacodynamic properties and the clinical pharmacology of murepavadin to
      date. Expert commentary: P. aeruginosa has an intrinsic resistance to many
      antibiotics due to high cellular impermeability and efficient drug efflux
      mechanisms, and the recent increase in prevalence of multidrug-resistant P.
      aeruginosa infections are particularly threatening in ICU settings. Murepavadin
      is a pathogen specific antimicrobial peptidomimetic with a novel, non-lytic
      mechanism of action, and is the first in class of outer membrane protein
      targeting antibiotics which are being developed. Murepavadin displays a potent in
      vitro activity including carbapenemase-producing and colistin-resistant P.
      aeruginosa. Murepavadin is active in pre-clinical animal models including
      infections with XDR isolates. The Pharmacokinetics is well characterized
      including subjects with impaired renal function and patients with VABP.
      Intravenous murepavadin is currently under clinical development for the treatment
      of HABP/VABP due to P. aeruginosa infection.

PMID- 29451044
TI  - Endemic and emerging acute virus infections in Indonesia: an overview of the past
      decade and implications for the future.
AB  - Being the largest archipelago country in the world, with a tropical climate and a
      unique flora and fauna, Indonesia habitats one of the most diverse biome in the
      world. These characteristics make Indonesia a popular travel destination, with
      tourism numbers increasing yearly. These characteristics also facilitate the
      transmission of zoonosis and provide ideal living and breading circumstances for
      arthropods, known vectors for viral diseases. A review of the past 10 years of
      literature, reports of the Ministry of Health, Republic of Indonesia and ProMED
      mail shows a significant increase in dengue infection incidence. Furthermore,
      chikungunya, Japanese encephalitis and rabies are proven to be endemic in
      Indonesia. The combination of cohort studies, governmental data and ProMED-mail
      reveals an integrated overview for those working in travel medicine and public
      health, focusing on both endemic and emerging acute virus infections. This review
      summarizes the epidemiology of acute virus infections in Indonesia, including
      outbreak reports, as well as public health response measurements and their
      potential or efficacy. Knowledge about human behaviour, animal reservoirs,
      climate factors, environment and their role in emerging virus infection are
      discussed. We aim to support public health authorities and health care policy
      makers in a One Health approach.

PMID- 29451045
TI  - Modified release paracetamol overdose: a prospective observational study (ATOM
      3).
AB  - BACKGROUND: Modified-release (MR) paracetamol is available in many countries as
      665 mg tablets of which 69% is MR and 31% is immediate release. There are
      concerns that MR paracetamol overdose has higher rates of liver injury despite
      standard treatment algorithms. The objective of this study was to describe the
      clinical characteristics and outcomes of acute MR paracetamol overdose. METHODS:
      Prospective observational study, recruiting patients from January 2013 to June
      2017, from five clinical toxicology units and calls to two Poisons Information
      Centres in Australia. Included were patients >14 years who ingested >=10 g or 200
      mg/kg (whichever is less) of MR paracetamol. Data collected included
      demographics, ingestion history, pathology results, treatments, and outcomes
      including hepatotoxicity (ALT >1000 U/L). RESULTS: In total, 116 patients were
      recruited, 85(73%) were female. The median dose ingested was 32 g (IQR: 20-49 g)
      and median time to presentation was 3 h (IQR: 2-9 h). 78(67%) had an initial
      paracetamol concentration above the nomogram line (150 mg/L at 4 h). A further
      12(10%) crossed the nomogram after repeat paracetamol measurements, of which five
      crossed after two non-toxic levels 4 h apart. Six had a double paracetamol peak,
      in three occurring >24 h post-ingestion. 113(97%) received acetylcysteine of
      which 67 received prolonged treatment beyond the standard 21 h. This was because
      of an elevated paracetamol concentration at the completion of acetylcysteine in
      39 (median paracetamol concentration 25 mg/L, IQR: 16-62 mg/L). 21 (18%)
      developed hepatotoxicity, including six treated within 8 h of ingestion.
      Activated charcoal and double doses of acetylcysteine did not significantly
      decrease the risk of hepatotoxicity. CONCLUSIONS: Drug regulatory authorities are
      considering restrictions on MR paracetamol preparations. Following an acute MR
      paracetamol overdose, this study found that many patients had a persistently
      elevated paracetamol concentrations, many required prolonged treatment and some
      developed liver injury despite early acetylcysteine treatment. Furthermore,
      activated charcoal and increased acetylcysteine did not appear to significantly
      alter the risk of liver injury. Hence, research into better treatment strategies
      is required. TRIAL REGISTRATION: Australian Toxicology Monitoring (ATOM) Study -
      Australian Paracetamol Project: ACTRN12612001240831 (ANZCTR) Date of
      registration: 23/11/2012.

PMID- 29451046
TI  - The need for patient-derived guidelines and curricula.

PMID- 29451047
TI  - National survey of Japanese patients with mevalonate kinase deficiency reveals
      distinctive genetic and clinical characteristics.
AB  - OBJECTIVES: Mevalonate kinase deficiency (MKD), a rare autosomal recessive
      autoinflammatory syndrome, is caused by disease-causing variants of the
      mevalonate kinase (MVK) gene. A national survey was undertaken to investigate
      clinical and genetic features of MKD patients in Japan. METHODS: The survey
      identified ten patients with MKD. Clinical information and laboratory data were
      collected from medical records and by direct interviews with patients, their
      families, and their attending physicians. Genetic analysis and measurement of MVK
      activity and urinary excretion of mevalonic acid were performed. RESULTS: None of
      the 10 patients harbored MVK disease-causing variants that are common in European
      patients. However, overall symptoms were in line with previous European reports.
      Continuous fever was observed in half of the patients. Elevated transaminase was
      observed in four of the 10 patients, two of whom fulfilled the diagnostic
      criteria for hemophagocytic lymphohistiocytosis. About half of the patients
      responded to temporary administration of glucocorticoids and NSAIDs; the others
      required biologics such as anti-IL-1 drugs. CONCLUSION: This is the first
      national survey of MKD patients in a non-European country. Although clinical
      symptoms were similar to those reported in Europe, the incidence of continuous
      fever and elevated transaminase was higher, probably due to differences in
      disease-causing variants.

PMID- 29451048
TI  - Impact of radon and combinatory radon/carbon dioxide spa on pain and
      hypertension: Results from the explorative RAD-ON01 study.
AB  - OBJECTIVES: Therapies with low doses of radon have beneficial effects on patients
      suffering from chronic painful degenerative and inflammatory diseases. We already
      showed that this is accompanied by systemic immune modulations. We here focus on
      pain-reducing effects of very low doses of radon by adding carbon dioxide water
      and its impact on heart rate variability (HRV), blood pressure and free radicals.
      METHODS: 97 of 103 patients receiving radon spa (1.200 Bq/l at 34  degrees C or
      600 Bq/l, 1 g/l CO2 at 34  degrees C) were monitored before and at three
      different time points after therapy. Individual pain perception was analyzed and
      the capability to process radicals. At each time point, the hypertensive patients
      (n = 46) were examined over 24 h for blood pressure and HRV. RESULTS: Long-term
      pain reduction was observed in the majority of patients. A modulation of
      superoxide dismutase was identified, presumably representing a priming effect for
      lowering radiation stress. Further, lowering of blood pressure, especially in
      those patients who additionally received carbon dioxide, was seen. Radon did in
      particular impact on HRV implying lasting relaxation effects. CONCLUSION:
      Radon/carbon dioxide spa efficiently reduces pain. In particular, patients
      simultaneously suffering from painful and cardiovascular diseases should be
      treated by combination of radon and CO2.

PMID- 29451049
TI  - The increase in bone mineral density by bisphosphonate with active vitamin D
      analog is associated with the serum calcium level within the reference interval
      in postmenopausal osteoporosis.
AB  - OBJECTIVES: To examine the factors associated with increase in lumbar spine bone
      mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog
      (aVD). METHODS: Two independent postmenopausal osteoporotic patients treated by
      BPs with aVD for 24 months (Study 1: n = 93, Study 2: n = 99) were
      retrospectively analyzed. RESULTS: In Study 1, LS-BMD of the patients
      significantly increased for 24 m (5.4%, p < .001). A multiple regression analysis
      among baseline characteristics revealed that serum calcium (sCa: 8.5-10.5 mg/dL)
      was associated with an increased LS-BMD by treatment (r2: 0.088, p = .02). While
      average sCa of the patients was 9.2 mg/dL before treatment, it increased time
      dependently to 9.6 mg/dL for 24 m by treatment. As each patient had their LS-BMD
      five times during the study, there were four instances of %LS-BMD in each
      patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike's
      information criterion value for the most appropriate cut-off levels of sCa for
      %LS-BMD by treatment every 6 m was 9.3 mg/dL. The %LS-BMD by treatment for 6 m
      during 24 m period in patients with sCa >=9.3 mg/dL (1.5%) was significantly
      higher than that in patients with sCa <9.3 mg/dL (0.8%, p = .038). The results of
      Study 2 were similar to those of Study 1, confirming the phenomena observed.
      CONCLUSION: sCa was associated with an increased LS-BMD by BPs with aVD.

PMID- 29451050
TI  - 9 years' follow-up of 168 pin-fixed supracondylar humerus fractures in children.
AB  - Background and purpose - The long-term outcome of pin-fixed supracondylar humerus
      fractures (SCHF) in children is not well known. We assessed the 7- to 12-year
      outcome in 168 children. Patients and methods - During 2002-2006, 210 domestic
      children (age 7 (1-14) years) with SCHF (Gartland III 79%, Gartland II 19%, and
      flexion type 2%) were pin fixed in Helsinki. 36 (17%) patients had a nerve palsy.
      Radiographic alignment was regarded as satisfactory in 81% of patients (Baumann
      angle (BA) within +/-10 of normal range and whose anterior humeral line (AHL)
      crossed the capitulum). After a mean follow-up of 9 (7-12) years, 168 (80%)
      patients answered a questionnaire regarding elbow appearance (scale 0-10),
      function (scale 0-10), and pain (scale 0-10), and symmetry of range of motion
      (ROM) and carrying angle (CA). 65 (31%) patients also attended a clinical follow
      up examination. Results - Mean subjective score for appearance was 8.7 (2-10) and
      for function 9.0 (2-10) (n = 168). Elbow ROM asymmetry was experienced by 28% and
      elbow CA asymmetry by 17% of the patients. Elbow pain was reported by 14%, and
      was more common in children with nerve injuries. Long-term outcome was good or
      excellent in 60/65 and CA in 56/65 of the follow-up visit patients using Flynn's
      criteria. BA exceeding normal values by 10 was associated with lower subjective
      outcome; AHL crossing point with the capitulum was not associated with outcome.
      Interpretation - Long-term subjective outcome is satisfactory with few exceptions
      if elbow ROM and CA are restored within 10 degrees  of the uninjured elbow.
      Radiographs at fracture union have little prognostic value. Nerve injuries can
      cause long-term pain.

PMID- 29451051
TI  - Influence of surgical approach on complication risk in primary total hip
      arthroplasty.
AB  - Background and purpose - Systematic comparisons of anterior approach (A) versus
      posterior approach (P) in primary total hip arthroplasty (THA) have largely
      focused on perioperative outcomes. In this systematic review with meta-analysis,
      we compared complication risk of A versus P in studies of primary THA with at
      least 1-year mean follow-up. Patients and methods - We performed a systematic
      review of prospective and retrospective studies with at least 1-year mean follow
      up that reported complications of A and P primary THA. Complications included
      infection, dislocation, reoperation, thromboembolic event, heterotopic
      ossification, wound complication, fracture, and nerve injury. Random effects meta
      analysis was used for all outcomes. Complication risk was reported as rate ratio
      (RR) to account for differential follow-up durations; values >1 indicated higher
      complication risk with A and values <1 indicated lower risk with A. Results - 19
      studies were included; 15 single-center comparative studies with 6,620 patients
      (2,278 A; 4,342 P) and 4 multicenter registries with 157,687 patients (18,735 A;
      138,952 P). Median follow-up was 16 (12-64) months) with A and 18 (12-110) months
      with P. Anterior approach was associated with lower rate of infection (RR =0.55,
      p = 0.002), dislocation (RR =0.65, p = 0.03), and reoperation (RR =0.84, p <
      0.001). No statistically significant differences were observed in rate of
      thromboembolic event (RR =0.59, p = 0.5), heterotopic ossification (RR =0.63, p =
      0.1), wound complication (RR =0.93, p = 0.8), or fracture (RR =1.0, p = 0.9).
      There was a higher rate of patient-reported nerve injury with A (RR =2.3, p =
      0.01). Interpretation - Comparing A with P in primary THA, A was associated with
      lower risk of reoperation, dislocation, and infection, but higher risk of patient
      reported nerve injury.

PMID- 29451052
TI  - Vlogging on: Could video blogging enhance medical education?

PMID- 29451053
TI  - The fate of silver nanoparticles in authentic human saliva.
AB  - The physicochemical properties of silver nanoparticles (AgNPs) in human whole
      saliva are investigated herein. In authentic saliva samples, AgNPs exhibit a
      great stability with over 70% of the nanomaterial remaining intact after a 24-h
      incubation in the presence of ~0.3 mM dissolved oxygen. The small loss of AgNPs
      from the saliva sample has been demonstrated to be a result of two processes:
      agglomeration/aggregation (not involving oxygen) and oxidative dissolution of
      AgNPs (assisted by oxygen). In authentic saliva, AgNPs are also shown to be more
      inert both chemically (silver oxidative dissolution) and electrochemically
      (electron transfer at an electrode) than in synthetic saliva or aqueous
      electrolytes. The results thus predict based on the chemical persistence (over a
      24-h study) of AgNPs in saliva and hence the minimal release of hazardous Ag+ and
      reactive oxygen species that the AgNPs are less likely to cause serious harm to
      the oral cavity but this persistence may enable their transport to other
      environments.

PMID- 29451054
TI  - Physician under supervision: UK medical students' perspectives.

PMID- 29451055
TI  - Early discontinuation of empirical antibacterial therapy in febrile neutropenia:
      the ANTIBIOSTOP study.
AB  - INTRODUCTION: Immediate empirical antibiotic therapy is mandatory in febrile
      chemotherapy-induced neutropenia, but its optimal duration is unclear, especially
      in patients with fever of unknown origin (FUO). OBJECTIVES: The primary objective
      of this 20-month prospective observational study was to evaluate the feasibility
      and safety of short-term antibiotic treatment in afebrile or febrile patients
      exhibiting FUO, irrespective of their neutrophil count. The secondary objective
      was to describe the epidemiology of all episodes of febrile neutropenia. METHODS:
      In the first phase of the study, empirical antibiotic therapy in FUO patients was
      stopped after 48 h of apyrexia, in accordance with European Conference on
      Infections in Leukaemia guidelines (n = 45). In the second phase of the study,
      antibiotics were stopped no later than day 5 for all FUO patients, regardless of
      body temperature or leukocyte count (n = 37). RESULTS: Two hundred and thirty
      eight cases of febrile neutropenia in 123 patients were included. Neither the
      composite endpoint (p = .11), nor each component (in-hospital mortality (p =
      .80), intensive care unit admission (p = 0.48), relapse of infection <=48 h after
      discontinuation of antibiotics (p = .82)) differed between the two FUO groups.
      Violation of protocol occurred in 17/82 episodes of FUO without any major impact
      on statistical results. Twenty-six (57.3%) and 22 (59.5%) FUO episodes did not
      relapse during hospital-stay (p = 1), and nine (20%) and five (13.5%) presented
      another FUO, respectively. One hundred and fifty-six episodes of febrile
      neutropenia (65.5%) were clinically or microbiologically documented, including 85
      bacteremia. CONCLUSIONS: These results suggest that early discontinuation of
      empirical antibiotics in FUO is safe for afebrile neutropenic patients.

PMID- 29451056
TI  - Epidemiology of injuries in Portuguese senior male rugby union sevens: a cohort
      prospective study.
AB  - OBJECTIVES: To assess the incidence, type and location of injuries sustained
      during the Portuguese rugby union sevens circuit. To investigate the influence of
      players' training loads on injury risk. METHODS: A prospective cohort study
      recording time-loss injuries was conducted with all teams competing in the
      Portuguese national rugby sevens circuit (eight from the top-tier and seven from
      the second-tier). Main outcome measures included: incidence rate, anatomical
      location, type, injury incident and severity. Data were also collected regarding
      players' training loads. Fisher's exact test was used to estimate the relative
      risk of suffering an injury during the sevens season and training sevens during
      the fifteens season. RESULTS: A total of 27 injuries were recorded corresponding
      to an incidence rate of 133.9 injuries per 1000 player match-hours. The average
      severity was 22.22 days. Contact events preceded 81.5% of injuries. Most injuries
      occurred in the lower limb (66.7%) and were joint/ligament or muscle/tendon
      injuries (85.1%). The association between injuries and lower volume of training
      during the sevens season was identified for the second-tier (p = 0.021). For the
      same level, an inverse relation between training hours and injury severity was
      also found (p = 0.008). Top-tier players training sevens and fifteens
      simultaneously during the year presented a significant increase of injury risk
      (relative risk = 3.2; p = 0.011). CONCLUSIONS: Injury incidence in our study is
      similar to that reported for international sevens, although severity is lower. An
      association between training loads and the occurrence of injuries was found for
      both tiers, although with differential results, thus reinforcing the need to
      customize players' preparation. Further studies at non-elite competitions are
      needed to gather significant data to accurately formulate future injury
      prevention protocols or recommend modifications to game laws or competition
      formats, aiming at players' welfare.

PMID- 29451057
TI  - Comparison between modified Dunn procedure and in situ fixation for severe stable
      slipped capital femoral epiphysis.
AB  - Background and purpose - The best treatment option for severe slipped capital
      femoral epiphysis (SCFE) is still controversial. We compared clinical and
      radiographic outcomes of modified Dunn procedure (D) and in situ fixation (S) in
      severe SCFE. Patients and methods - We retrospectively compared D and S, used for
      severe stable SCFE (posterior sloping angle (PSA) > 50 degrees ) in 29 patients
      (15 D; 14 S). Propensity analysis and inverse probability of treatment weights
      (IPTW) to adjust for baseline differences were performed. Patients were followed
      for 2-7 years. Results - Avascular necrosis (AVN) occurred in 3 patients out of
      15, after D, causing conversion to total hip replacement (THR) in 2 cases. In S,
      1 hip developed chondrolysis, requiring THR 3 years after surgery. 3 symptomatic
      femoroacetabular impingements (FAI) occurred after S, requiring corrective
      osteotomy in 1 hip, and osteochondroplasty in another case. The risk of early re
      operation was similar between the groups. The slippage was corrected more
      accurately and reliably by D. The Nonarthritic Hip Score was similar between
      groups, after adjusting for preoperative and postoperative variables.
      Interpretation - Although D was superior to S in restoring the proximal femoral
      anatomy, without increasing the risk of early re-operation, some concern remains
      regarding the potential risk of AVN in group D.

PMID- 29451058
TI  - Developmental differences in stress responding after repeated underwater trauma
      exposures in rats.
AB  - Adolescence is a distinct developmental period characterized by behavioral and
      physiological maturation. Rapid ongoing changes during neurodevelopment in
      particular present potential opportunities for stress to have lasting effects on
      longitudinal outcomes of behavioral and neuroendocrine function. While adult
      stress effects on outcomes during adulthood have been characterized, little is
      known about the lasting effects of adolescent repeated stressor exposure on
      outcomes during adolescence. We have previously reported different stress
      responses in adolescent rats relative to adult rats, including a blunted fear
      response outcome in adulthood in rats stressed during adolescence. The present
      study characterized the ontogeny of behavioral and neuroendocrine responses to
      eight underwater trauma (UWT) exposures in rats over a two week poststress time
      period during adolescence (P34) or adulthood (P83) relative to age-matched
      control groups that underwent eight swimming episodes without UWT. Repeated UWT
      exposures starting in adolescence, but not adulthood, resulted in adverse
      behavioral responses on the elevated plus maze 1 day post-stress. Corticosterone
      responses did not differ between UWT-exposed and controls for either age group at
      1 day or at 7 days poststress, although there was an effect of age on
      corticosterone levels. We conclude that repeated UWT stress events have a
      lasting, negative behavioral effect on adolescent rats that is not observed in
      adult rats after the two-week exposure window. These results suggest that
      neurophysiological mechanisms underlying recovery from a repeated stressor are
      immature in adolescence relative to adulthood in rats.

PMID- 29451059
TI  - 'Oncokompas', a web-based self-management application to support patient
      activation and optimal supportive care: a feasibility study among breast cancer
      survivors.
AB  - BACKGROUND: Cancer survivors have to deal with symptoms related to cancer and its
      treatment. In Oncokompas, cancer survivors monitor their quality of life by
      completing patient reported outcome measures (PROMs), followed by personalized
      feedback, self-care advice, and supportive care options to stimulate patient
      activation. The aim of this study was to investigate feasibility and pretest
      posttest differences of Oncokompas including a newly developed breast cancer (BC)
      module among BC survivors. MATERIAL AND METHODS: A pretest-posttest design was
      used. Feasibility was investigated by means of adoption, usage, and satisfaction
      rates. Several socio-demographic and clinical factors, and health-related quality
      of life (HRQOL) were explored that might be associated with patient satisfaction.
      Barriers and facilitators of Oncokompas feasibility were investigated by
      evaluating nurse consultation reports. Differences in patient activation (Patient
      Activation Measure) and patient-physician interaction (Perceived Efficacy in
      Patient-Physician Interactions) before and after Oncokompas use were
      investigated. RESULTS: In total, 101 BC survivors participated. Oncokompas had an
      adoption rate of 75%, a usage rate of 75-84%, a mean satisfaction score of 6.9
      (range 0-10) and a Net Promoter Score (NPS) of -36 (range -100-100) (N = 68). The
      BC module had a mean satisfaction score of 7.6. BC survivors who received surgery
      including chemotherapy and/or radiotherapy were significantly more satisfied with
      Oncokompas than BC survivors with surgery alone (p = .013). Six facilitators and
      10 barriers of Oncokompas feasibility were identified. After using Oncokompas, BC
      survivors scored significantly higher on patient activation (p = .007; r = .24),
      but not on patient-physician interaction (p = .75). CONCLUSION: Oncokompas
      including a BC module is considered feasible, but needs further optimization to
      increase user satisfaction. This study shows the value of tailoring eHealth
      applications for cancer survivors to their specific tumor type. Oncokompas
      including the BC module seems to improve patient activation among BC survivors.

PMID- 29451061
TI  - Neck-Tongue Syndrome: An Underrecognized Childhood Onset Cephalalgia.
AB  - Neck-tongue syndrome is a rarely reported headache disorder characterized by
      occipital and/or upper neck pain triggered by sudden rotatory head movement and
      accompanied by abnormal sensation and/or posture of the ipsilateral tongue.
      Although onset is thought to be in childhood, most of the limited number of cases
      reported so far were adults. Here the authors describe 3 cases, 2 girls and 1
      boy, with neck-tongue syndrome. In each child additional headache symptoms
      occurred, headache improved over time in all, spontaneously in 2 and coinciding
      with gabapentin treatment in the other. Investigations were consistently
      unremarkable. Review of the literature reveals a usually self-limiting disorder,
      with early onset and variable additional features. Awareness of neck-tongue
      syndrome among pediatric neurologists and other practitioners is important, to
      allow for timely diagnosis and informed management of an underreported headache
      disorder with childhood onset.

PMID- 29451060
TI  - Cord blood buffy coat DNA methylation is comparable to whole cord blood
      methylation.
AB  - Cord blood DNA methylation is associated with numerous health outcomes and
      environmental exposures. Whole cord blood DNA reflects all nucleated blood cell
      types, while centrifuging whole blood separates red blood cells, generating a
      white blood cell buffy coat. Both sample types are used in DNA methylation
      studies. Cell types have unique methylation patterns and processing can impact
      cell distributions, which may influence comparability. We evaluated differences
      in cell composition and DNA methylation between cord blood buffy coat and whole
      cord blood samples. Cord blood DNA methylation was measured with the Infinium
      EPIC BeadChip (Illumina) in eight individuals, each contributing buffy coat and
      whole blood samples. We analyzed principal components (PC) of methylation,
      performed hierarchical clustering, and computed correlations of mean-centered
      methylation between pairs. We conducted moderated t-tests on single sites and
      estimated cell composition. DNA methylation PCs were associated with individual
      (PPC1 = 1.4 * 10-9; PPC2 = 2.9 * 10-5; PPC3 = 3.8 * 10-5; PPC4 = 4.2 * 10-6; PPC5
      = 9.9 * 10-13, PPC6 = 1.3 * 10-11) and not with sample type (PPC1-6>0.7). Samples
      hierarchically clustered by individual. Pearson correlations of mean-centered
      methylation between paired samples ranged from r = 0.66 to r = 0.87. No
      individual site significantly differed between buffy coat and whole cord blood
      when adjusting for multiple comparisons (five sites had unadjusted P<10-5).
      Estimated cell type proportions did not differ by sample type (P = 0.46), and
      estimated proportions were highly correlated between paired samples (r = 0.99).
      Differences in methylation and cell composition between buffy coat and whole cord
      blood are much lower than inter-individual variation, demonstrating that both
      sample preparation types can be analytically combined and compared.

PMID- 29451062
TI  - Exploratory rearing: a context- and stress-sensitive behavior recorded in the
      open-field test.
AB  - Stressful experiences are linked to anxiety disorders in humans. Similar effects
      are observed in rodent models, where anxiety is often measured in classic
      conflict tests such as the open-field test. Spontaneous rearing behavior, in
      which rodents stand on their hind legs to explore, can also be observed in this
      test yet is often ignored. We define two forms of rearing, supported rearing (in
      which the animal rears against the walls of the arena) and unsupported rearing
      (in which the animal rears without contacting the walls of the arena). Using an
      automated open-field test, we show that both rearing behaviors appear to be
      strongly context dependent and show clear sex differences, with females rearing
      less than males. We show that unsupported rearing is sensitive to acute stress,
      and is reduced under more averse testing conditions. Repeated testing and
      handling procedures lead to changes in several parameters over varying test
      sessions, yet unsupported rearing appears to be rather stable within a given
      animal. Rearing behaviors could therefore provide an additional measure of
      anxiety in rodents relevant for behavioral studies, as they appear to be highly
      sensitive to context and may be used in repeated testing designs.

PMID- 29451063
TI  - Epithelial tumors: Growing from within.
AB  - The growth of epithelial tumors is often governed by cell interactions with the
      surrounding stroma. Drosophila has been instrumental in identifying the relevant
      molecular elements mediating these interactions. Of note is the role of the TNF
      ligand Eiger, released from recruited blood cells, in activating the JNK tumor
      promoting pathway in epithelial tumors. JNK drives the transcriptional induction
      of mitogenic molecules, matrix metalloproteases and systemic signals that lead to
      tumor growth, tissue invasiveness and malignancy. Here we review our findings on
      a tumor-intrinsic, Eiger- and stroma-independent mechanism that contributes to
      the unlimited growth potential of tumors caused either by chromosomal instability
      or impaired cell polarity. This newly identified mechanism, which was revealed in
      an experimental condition in which contacts between tumor cells and wild-type
      epithelial cells were minimized, relies on interactions between functionally
      distinct tumor cell populations that activate JNK in a cell-autonomous manner. We
      discuss the impact of cell interaction-based feedback amplification loops on the
      unlimited growth potential of epithelial tumors. These findings are expected to
      contribute to the identification of the relevant cell populations and molecular
      mechanisms to be targeted in drug therapy.

PMID- 29451064
TI  - Inactivation gating of Kv7.1 channels does not involve concerted cooperative
      subunit interactions.
AB  - Inactivation is an intrinsic property of numerous voltage-gated K+ (Kv) channels
      and can occur by N-type or/and C-type mechanisms. N-type inactivation is a fast,
      voltage independent process, coupled to activation, with each inactivation
      particle of a tetrameric channel acting independently. In N-type inactivation, a
      single inactivation particle is necessary and sufficient to occlude the pore. C
      type inactivation is a slower process, involving the outermost region of the pore
      and is mediated by a concerted, highly cooperative interaction between all four
      subunits. Inactivation of Kv7.1 channels does not exhibit the hallmarks of N- and
      C-type inactivation. Inactivation of WT Kv7.1 channels can be revealed by hooked
      tail currents that reflects the recovery from a fast and voltage-independent
      inactivation process. However, several Kv7.1 mutants such as the pore mutant
      L273F generate an additional voltage-dependent slow inactivation. The subunit
      interactions during this slow inactivation gating remain unexplored. The goal of
      the present study was to study the nature of subunit interactions along Kv7.1
      inactivation gating, using concatenated tetrameric Kv7.1 channel and introducing
      sequentially into each of the four subunits the slow inactivating pore mutation
      L273F. Incorporating an incremental number of inactivating mutant subunits did
      not affect the inactivation kinetics but slowed down the recovery kinetics from
      inactivation. Results indicate that Kv7.1 inactivation gating is not compatible
      with a concerted cooperative process. Instead, adding an inactivating subunit
      L273F into the Kv7.1 tetramer incrementally stabilizes the inactivated state,
      which suggests that like for activation gating, Kv7.1 slow inactivation gating is
      not a concerted process.

PMID- 29451066
TI  - Psychometric properties of MDHAQ/RAPID3 in patients with systemic lupus
      erythematosus.
AB  - Background The Multidimensional Health Assessment Questionnaire (MDHAQ) is a
      patient-reported outcome (PRO) tool that includes the Routine Assessment of
      Patient Index Data 3 (RAPID3), an index that can be calculated at the point of
      care. The objective of this study was to perform psychometric analyses of
      MDHAQ/RAPID3 to study its measurement properties in systemic lupus erythematosus
      (SLE). Methods The MDHAQ was completed by 161 SLE patients in routine care, along
      with LupusPRO (a disease-specific PRO). The SLE disease-specific activity index
      (SELENA-SLEDAI) and damage (SDI) were assessed. Data from 70 patients with
      rheumatoid arthritis who had completed MDHAQ during their routine medical care
      were used as controls to compare the results of Physical Function (FN) domain
      exploratory factor analysis. Internal consistency reliability (ICR) for FN items
      was calculated using Cronbach's alpha. Validity of MDHAQ/RAPID3 was evaluated for
      content validity and construct validity. Responsiveness of the RAPID3 to changes
      in disease activity anchors was assessed. Results The ICR of the 10 physical
      function items on Cronbach's alpha was 0.88. Exploratory factor analysis revealed
      cross-loadings of three FN items. RAPID3 showed a strong correlation with
      LupusPRO health-related quality of life score (rho -0.68 ( p < 0.001)),
      indicating convergent validity. RAPID3 scores did not correlate with disease
      activity indices or SDI. After adjustment for fibromyalgia status, a weak
      correlation with the Physician's Global Assessment (PGA) (rho = 0.31, p = 0.008)
      was noted. RAPID3 could differentiate between SLE patients based on flare status.
      RAPID3 was not responsive to changes in PGA, SELENA-SLEDAI or SELENA-Flare Index.
      Conclusions MDHAQ/RAPID3 has fair reliability and validity in SLE.

PMID- 29451065
TI  - Shoulder and arm muscle activity during elastic band exercises performed in a
      hospital bed.
AB  - OBJECTIVE: Muscle atrophy is a common side-effect of bed rest during
      hospitalization. However, resistance training may minimize or even prevent these
      complications. Therefore, we evaluated the efficiency of four upper-body elastic
      resistance exercises that could be performed while lying or sitting in a hospital
      bed. METHODS: Twenty-two healthy subjects performed three repetitions of each
      exercise in a supine and seated position with a perceived intensity of 3 (low)
      and 8 (high) on the Borg CR10 Scale. Surface electromyography was collected from
      12 shoulder and arm muscles (e.g. trapezius, deltoideus, and biceps brachii), and
      normalized to a maximal voluntary isometric contraction (nEMG). RESULTS: During
      all exercises performed at high intensity, moderate (>40%) to high (>60%) levels
      of nEMG were found for the majority of the analysed muscles, e.g. deltoideus
      (from 37% to 69%, median 57.5%), trapezius (from 43% to 66%, median 51%), and
      infraspinatus (from 54% to 66%, median 59%), with the exception of pectoralis
      major (from 29% to 47%, median 39.5%) and latissimus dorsi (from 15% to 22%,
      median 18.5%). No significant differences were found between the supine and
      seated positions for any of the exercises. CONCLUSION: This study showed that
      high levels of shoulder and arm muscle activity can be achieved while lying or
      sitting in a hospital bed using appropriate exercises with elastic bands. The
      data presented here can be used by physiotherapists as a guideline for selecting
      suitable and effective strengthening exercises during in-hospital rehabilitation
      to counteract bed-rest related muscle atrophy in the upper body.

PMID- 29451067
TI  - Combined detection of uMCP-1 and uTWEAK for rapid discrimination of severe lupus
      nephritis.
AB  - Reliable markers for the rapid discrimination of severe renal damage remain a
      vital concern for lupus nephritis (LN). To determine a better tool for kidney
      damage detection, the present study compared the evaluation ability of novel
      urinary cytokines and chemokines (namely urinary monocyte chemoattractant protein
      1 (uMCP-1), tumor necrosis factor-like weak inducer of apoptosis (uTWEAK)) with
      traditional serum or urinary markers (namely urinary alpha 1-microgrobulin
      (ualpha1-MG), beta 2-microglobulin (ubeta2-MG) and serum complement C3 (C3),
      complement C4 (C4), creatinine (Cr), blood urea nitrogen (BUN) and cystatin C
      (Cys C)) in discriminating LN renal damage. Correlations between markers with
      Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) renal SLEDAI scores,
      biopsy activity index (BAI) and biopsy chronicity index (BCI) scores were
      evaluated. Receiver operating characteristic (ROC) curves were generated to
      evaluate a single or combined model in discriminating active renal involvement
      (rSLEDAI scores > 0) and patients with poor pathological outcome (BAI scores >=
      7). uMCP-1 and uTWEAK possess higher correlation coefficients with renal damage
      and larger areas under ROC curves (AUCs) than other markers. A combined model of
      uMCP-1 and uTWEAK showed an AUC of 0.887, sensitivity of 86.67% and specificity
      of 80.00% to discriminate active LN, and an AUC of 0.778, sensitivity of 75.00%
      and specificity of 81.82% to discriminate LN with poor outcome, which are better
      than the utility of any markers individually.

PMID- 29451068
TI  - Increased visceral adipose tissue and altered adiposity distribution in
      premenopausal lupus patients: correlation with cardiovascular risk factors.
AB  - Objective Visceral adipose tissue (VAT) correlates with cardiovascular risk
      factors and has never been assessed in systemic lupus erythematosus (SLE). Our
      aim was to evaluate VAT in premenopausal SLE patients. Methods Sixty-three
      premenopausal SLE patients and 186 age-matched healthy women were included.
      Demographic, anthropometric, disease and treatment parameters were evaluated. VAT
      was measured by dual X-ray absorptiometry (DXA) with APEX 4.0 software. Results
      SLE patients had a disease duration of 5.25 +/- 3.80 years, SLEDAI activity score
      of 4.35 +/- 5.13, SLICC/ACR-DI of 0.70 +/- 0.80, current prednisone dose of 11.60
      +/- 12.10 mg/day and cumulative glucocorticoid dose of 22.34 +/- 12.94 g.
      Overweight/obese SLE patients and controls had similar VAT parameters ( p >
      0.05). Among individuals with BMI <25 kg/m2, SLE patients and controls had
      similar weight, fat mass and fat percentage ( p > 0.05) but patients had higher
      values of VAT parameters (VAT mass: 260.60 +/- 117.23 vs. 194.77 +/- 71.42 g, p =
      0.001; VAT area: 54.05 +/- 24.30 vs. 40.40 +/- 14.82 cm2, p = 0.001; VAT volume:
      281.75 +/- 126.81 vs. 210.61 +/- 77.29 cm3, p = 0.001) and trunk/limb fat mass
      ratio (0.78 +/- 0.21 vs. 0.67 +/- 0.12, p = 0.002) compared to controls. In SLE,
      VAT area correlated with weight ( r = 0.66, p < 0.001), non-HDL cholesterol ( r =
      0.53, p < 0.001), LDL cholesterol ( r = 0.48, p < 0.001) and triglycerides ( r =
      0.33, p = 0.008), but not with disease duration, SLEDAI, SLICC/ACR-DI or current
      glucocorticoid use ( p > 0.05). Conclusion This study provides original evidence
      that SLE is associated with increased VAT and altered adiposity distribution. The
      correlation with traditional risk factors for cardiovascular disease, independent
      of current glucocorticoid dose and disease activity, suggests the role of
      visceral fat as an additional tool for risk assessment in these young patients.

PMID- 29451069
TI  - Arthritis and use of hydroxychloroquine associated with a decreased risk of
      macrophage activation syndrome among adult patients hospitalized with systemic
      lupus erythematosus.
AB  - Background Macrophage activation syndrome (MAS) is an uncommon but serious
      complication of systemic lupus erythematosus (SLE). We aimed to identify factors
      associated with MAS among adult hospitalized SLE patients. Methods Within the
      Brigham and Women's Hospital (BWH) Lupus Center Registry, we identified adult SLE
      patients > age 17 who had been hospitalized from 1970 to 2016, with either
      ferritin > 5000 ng/ml during admission or "macrophage activation syndrome" or
      "MAS" in discharge summary. We confirmed MAS by physician diagnosis in medical
      record review. We matched each hospitalized SLE patient with MAS to four SLE
      patients hospitalized without MAS (by SLE diagnosis date +/-1 year). We employed
      conditional logistic regression models to identify clinical factors associated
      with MAS among hospitalized SLE patients. Results Among 2094 patients with
      confirmed SLE, we identified 23 who had a hospitalization with MAS and compared
      them to 92 hospitalized without MAS. Cases and controls had similar age at SLE
      diagnosis (29.0 vs. 30.5, p = 0.60), and hospital admission (43.0 vs. 38.3, p =
      0.80), proportion female (78% vs. 84%, p = 0.55), and time between SLE diagnosis
      and hospitalization (1971 vs. 1732 days, p = 0.84). Arthritis (OR 0.04 (95% CI
      0.004-0.35)) and hydroxychloroquine use (OR 0.18 (95% CI 0.04-0.72)) on admission
      were associated with decreased MAS risk. Admission Systemic Lupus Erythematosus
      Disease Activity Index scores (30 vs. 19, p = 0.002) and lengths of stay (16 days
      vs. 3 days, p < 0.0001) were much higher among cases. Death during
      hospitalization was 19% among cases and 3% among controls ( p = 0.03).
      Conclusions In this case-control study of hospitalized adult SLE patients,
      arthritis and hydroxychloroquine use at hospital admission were associated with
      decreased MAS risk. Further studies are needed to validate these factors
      associated with lowered MAS risk.

PMID- 29451070
TI  - Confounders other than comorbidity explain survival differences in Danish and
      Swedish ovarian cancer patients - a comparative cohort study.
AB  - OBJECTIVE: Danish ovarian cancer (OC) patients have previously been found to have
      worse prognosis than Swedish patients, and comorbidity has been suggested as a
      possible explanation for this survival difference. We aimed to investigate the
      prognostic impact of comorbidity in surgically treated OC patients in Denmark and
      Sweden. METHODS: This comparative cohort study was based on data from 3118
      surgically treated OC patients diagnosed in 2012-2015. The Swedish subcohort (n =
      1472) was identified through the Swedish National Quality Register of
      Gynecological Surgery, whereas the Danish subcohort (n = 1646) originated from
      the Danish Gynecological Cancer Database. The clinical databases have high
      coverage and similar variables included. Comorbidity was classified according to
      the Ovarian Cancer Comorbidity Index and overall survival was the primary
      outcome. Data were analyzed using Kaplan Meier and Cox regression analyses.
      Multiple imputation was used to handle missing data. RESULTS: We found comparable
      frequencies of the following comorbidities: Hypertension, diabetes and 'Any
      comorbidity'. Arteriosclerotic cardiac disease and chronic pulmonary disease were
      more common among Swedish patients. Univariable survival analysis revealed a
      significant better prognosis for Swedish than for Danish patients (HR 0.84 [95%
      CI 0.74-0.95], p < .01). In adjusted multivariable analysis, Swedish patients had
      nonsignificant better prognosis compared to Danish patients (HR 0.91 [95% CI 0.80
      1.04], p = .16). Comorbidity was associated with survival (p = .02) but
      comorbidity did not explain the survival difference between the two countries.
      CONCLUSIONS: Danish OC patients have a poorer prognosis than patients in Sweden
      but the difference in survival seems to be explained by other factors than
      comorbidity.

PMID- 29451071
TI  - Childhood emotional invalidation and right hemispheric mu suppression during a
      pain empathy task: An EEG study.
AB  - Empathy is a critical aspect of social behavior, and impairment in empathic
      processing is linked to hindered social interactions and several disorders.
      Despite much interest in this topic, our understanding of the developmental and
      neural involvement for empathic processing is limited. Recent evidence suggests
      the Mirror Neuron System (MNS) may play a role in this behavior, and that mu
      rhythm suppression found over the sensorimotor cortices may be a proxy for the
      MNS. Therefore, we aimed to measure mu rhythm oscillations in response to
      empathic processing during observation of painful action-based situations using
      electroencephalogram (EEG). Our second goal was to examine how perceived parental
      emotional invalidation (EI) during childhood may relate to empathy and influence
      mu suppression. Our results showed that mu rhythm suppression was strongest over
      the right hemisphere. EI had a significant influence on this suppression between
      painful and non-painful images, and was negatively correlated with behavioral
      measures of empathy. Our findings suggest that perceived childhood EI may
      decrease empathizing abilities and influence neural responses to the painful
      experiences of others. Implications from this study could entail clinical
      intervention targeted at emotional invalidation to foster the healthy development
      of empathy.

PMID- 29451073
TI  - Mental Health Problems Among Whistleblowers: A Comparative Study.
AB  - Whistleblowers play a very important and indispensable role in society and health
      care sector, but their act may elicit retaliation and other negative effects,
      which may impact their mental health. The main aim of the present comparative
      study is to assess to what extent whistleblowers ( N = 27) more often suffer from
      severe mental health problems than other population-based groups in the
      Netherlands, i.e., matched controls ( N = 135), cancer patients ( N = 130),
      persons with (partial) work disabilities ( N = 194), physically "healthy" persons
      ( N = 200), and general population ( N = 1026), using the 36-Item Short-Form
      Health Survey scales (for general mental health) and the Symptom Checklist-90
      Revised scales (for specific mental health problems: depression, anxiety,
      agoraphobia, interpersonal sensitivity and distrust, and sleeping problems).
      Logistic regression analyses showed that the prevalence of general mental health
      problems was much higher than among matched controls and people with work
      disabilities but similar to cancer patient when controlling for demographics.
      About 85% suffered from severe to very severe anxiety, depression, interpersonal
      sensitivity and distrust, agoraphobia symptoms, and/or sleeping problems, and 48%
      reached clinical levels of these specific mental health problems. These specific
      mental health problems were much more prevalent than among the general
      population.

PMID- 29451072
TI  - Social Support for Exercise as a Predictor of Weight and Physical Activity Status
      Among Puerto Rican and Mexican Men: Results From the Latino Men's Health
      Initiative.
AB  - Social support is an important factor in increasing positive health outcomes and
      positive health behaviors across a variety of disease states including obesity.
      However, research examining the relationship between social support for exercise
      and weight and physical activity status, particularly among Latino men, is
      lacking. This paper examined whether social support for exercise predicted weight
      and physical activity status and whether the direction of these relationships
      differ as a function of Hispanic/Latino background (Puerto Rican/Mexican).
      Participants were 203 men who participated in a National Institutes of Health
      (NIH)-funded study addressing culture- and obesity-related variables. Both family
      participation social support and f amily rewards and punishment social support
      predicted higher weight status ( p < .005 and p < .05, respectively). Friend
      participation social support did not predict weight status. The direction of the
      relationship between weight status and family participation social support,
      family rewards and punishment social support, and friend participation social
      support did not significantly differ as a function of Hispanic/Latino background.
      The direction of the relationship between physical activity status and family
      participation social support, family rewards and punishment social support, and
      friend participation social support did not significantly differ as a function of
      Hispanic/Latino background. Findings suggest that increased social support for
      exercise from family members may be focused on those who need it most-overweight
      and obese participants. Additional research is needed to explore sociocultural
      factors that may promote social support, physical activity, and weight loss and
      maintenance in Puerto Rican and Mexican men.

PMID- 29451074
TI  - Negative emotional face perception is diminished on a very early level of
      processing in autism spectrum disorder.
AB  - Deficits in facial affect recognition (FAR) are often reported in autism spectrum
      disorder (ASD) due to inappropriate visual search strategies. It is unclear,
      however, whether or not deficits in subliminal FAR are still present in autism
      when visual focus is controlled. Thirteen persons with ASD and 13 healthy
      participants took part in this experiment. Supraliminal FAR was assessed using a
      standardized, computer-aided test. Subliminal FAR was obtained by an emotional
      face priming paradigm. By using an eye-tracking technique, it was assured that
      the initial visual focus was on the eyes of the prime. Persons with ASD showed
      worse FAR in supraliminal face recognition. Although controlled for initial gaze
      direction, participants also showed reduced negative face priming. These data
      confirm that FAR is disturbed already on a pre-attentive level in autism.

PMID- 29451075
TI  - Short-term outcomes of preoperative intra-aortic balloon pump use in patients
      undergoing adjunctive coronary endarterectomy: a retrospective observational
      study.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) combined with coronary
      endarterectomy (CE) can be associated with high operative mortality and
      morbidity. An intra-aortic balloon pump (IABP) has been the most widely used
      mechanical circulatory support device during perfusion treatment. However, the
      benefits of preoperative IABP in CABG combined with CE remain unknown. We
      conducted a retrospective observational study to evaluate the efficacy of
      preoperative IABP therapy in patients undergoing adjunctive right coronary artery
      (RCA) endarterectomy. METHODS: Between May 2013 and May 2016, 120 patients
      undergoing off-pump coronary artery bypass grafting (OPCABG) with RCA
      endarterectomy who received preoperative IABP support (IABP group, n=56) or who
      did not receive preoperative IABP support (control group, n=64) were evaluated
      retrospectively. RESULTS: Patients in the IABP group had a significantly lower
      mean preoperative ejection fraction and a significantly higher mean EuroSCORE
      (both <0.05). The incidence of inferior myocardial infarction (MI) was
      significantly lower in the IABP group than in the control group (3.6% vs 15.6%,
      RR = 0.23, 95% CI 0.05-1.00, p=0.03). Hospital mortality was similar in the two
      groups (3.6% vs 4.7%, RR= 0.76, 95% CI 0.13-4.40, p=0.76). There were no
      significant differences between the two groups with respect to the rates of
      prolonged ventilation, low cardiac output syndrome, renal failure requiring
      dialysis, re-operation for bleeding or IABP-related complications. Preoperative
      IABP may be a protective factor of inferior MI (HR = 0.031, 95% CI 0.004-0.211,
      p<0.001) Conclusions: The preoperative use of IABP could reduce the incidence of
      postoperative MI in patients undergoing CABG with CE and seemed to shift high
      risk patients into a lower-risk category.

PMID- 29451076
TI  - Similarity and decision time in preferential choice.
AB  - Choice option similarity is a key contextual variable in multiattribute choice.
      Based on theories of preference accumulation, we predicted that decision times
      would be longer when the available choice options were similar compared with when
      they were dissimilar, controlling for the relative desirabilities of the options.
      We tested for the relationship between similarity and decision time in an
      experiment involving incentivised binary choices between items of equivalent
      desirability and found that our predictions were confirmed. Our results show how
      the effects of contextual factors on key decision variables can be accurately
      predicted by existing computational theories of decision-making.

PMID- 29451077
TI  - Intravitreal Aflibercept Versus Ranibizumab for Wet Age-Related Macular
      Degeneration: A Cost-effectiveness Analysis.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision
      loss in the United States. The most severe vision loss occurs in patients with
      neovascular AMD, known as wet AMD (wAMD). The most commonly used antivascular
      endothelial growth factor (VEGF) therapies approved by the FDA to treat patients
      with wAMD are ranibizumab, 0.5 mg administered by intravitreal injection once a
      month (approximately every 28 days), and intravitreal aflibercept injection
      (IAI), 2 mg every 4 weeks (monthly) for the first 12 weeks (3 months), followed
      by IAI 2 mg once every 8 weeks (2 months). Given the similar efficacy and safety
      profiles between IAI and ranibizumab, their associated costs and comparative cost
      effectiveness are key factors in determining which one represents a more rational
      investment of scarce health care resources to help address the increasing cost of
      prescription drugs in the United States, a source of concern for patients,
      prescribers, payers, and policymakers. OBJECTIVE: To assess the cost
      effectiveness of intravitreal aflibercept injection 2 mg every 8 weeks after 3
      initial monthly doses (IAI 2q8) versus ranibizumab 0.5 mg monthly (Rq4) and pro
      re nata (PRN) in the treatment of patients with wAMD from a U.S. payer
      perspective. METHODS: A Markov cohort model was developed to estimate the
      lifetime quality-adjusted life-years (QALYs) and costs of treating patients with
      wAMD with IAI 2q8, Rq4, and ranibizumab PRN. The model considered changes in best
      corrected visual acuity in the affected and fellow eyes over time, and the effect
      of blindness on mortality. Efficacy for IAI 2q8 and Rq4 was from VIEW 1 and VIEW
      2 studies and from the Comparison of AMD Treatments Trials for ranibizumab PRN.
      Utilities and costs (in 2016 U.S. dollars) were from published literature. Health
      outcomes and costs were discounted at an annual rate of 3%. RESULTS: Over a
      lifetime, IAI 2q8 provided equal health benefits with Rq4 (5.44 QALYs) at a lower
      total cost ($33,745 vs. $48,031) as a result of fewer injections. IAI 2q8 yielded
      slightly greater QALYs versus ranibizumab PRN (5.44 vs. 5.40) at a slightly
      higher cost ($33,745 vs. $33,652), with an incremental cost per QALY gained of
      $2,583. Results were sensitive to variations in drug acquisition costs and number
      of injections of both drugs and the baseline age of the cohort. CONCLUSIONS: IAI
      2q8 can be cost saving and cost-effective compared with Rq4 and ranibizumab PRN
      for the treatment of wAMD in the United States. DISCLOSURES: This study was
      funded by Regeneron Pharmaceuticals, the manufacturer of aflibercept. Hernandez,
      Lanitis, Cele, and Toro-Diaz are employed by Evidera, which received funding from
      Regeneron Pharmaceuticals to conduct this study. Gibson and Kuznik are employed
      by and own stock in Regeneron Pharmaceuticals. Study concept and design were
      contributed by Hernandez, Lanitis, Kuznik, and Toro-Diaz. Cele, Toro-Diaz, and
      Lanitis took the lead in data collection, with assistance from the other authors.
      Data interpretation was performed by Cele, Toro-Diaz, Hernandez, Lanitis, and
      Kuznik. The manuscript was written by Hernandez, Lanitis, Gibson, Kuznik, and
      Cele and revised by Hernandez, Gibson, Kuznik, and Lanitis.

PMID- 29451078
TI  - Oncologists' Perceptions of Drug Affordability Using NCCN Evidence Blocks:
      Results from a National Survey.
AB  - BACKGROUND: The increasing prevalence of cancer coupled with approvals of new
      drugs and technologies used in therapy have brought increased scrutiny to the
      cost and value of treatments in oncology. To address the rising concern about
      oncology drug costs, several organizations have developed value frameworks to
      help assess the value of oncology regimens. The objective of this study was to
      assess oncologists' perceptions, awareness, and knowledge of all oncology value
      frameworks in the United States and to understand oncologists' perceptions of
      affordability in the context of National Comprehensive Cancer Network (NCCN)
      Evidence Blocks. OBJECTIVES: To (a) assess oncologists' awareness, knowledge,
      perceptions, and ratings of the American Society of Clinical Oncology Value
      Framework (AVF), the Institute for Clinical and Economic Review (ICER) value
      framework, NCCN Evidence Blocks, and Memorial Sloan Kettering Cancer Center's
      DrugAbacus; (b) assess oncologists' knowledge and perceptions of drug
      affordability as defined by the NCCN Evidence Blocks methodology; and (c)
      determine the factors that influence drug affordability ratings. METHODS: Data
      were collected from an electronic cross-sectional survey of 200 U.S.-based
      oncologists from a variety of practice settings. Oncologists were asked about
      their knowledge and perceptions of 4 value frameworks-NCCN Evidence Blocks, AVF,
      the ICER value framework, and DrugAbacus. Using NCCN Evidence Blocks, oncologists
      were asked to rate a variety of hypothetical cancer therapies and assign costs
      (in U.S. dollars) to the 5 levels of affordability. Additional questions that
      assessed perceived patient out-of-pocket (OOP) costs and comfort level in
      assessing affordability were also included in the survey. RESULTS: Oncologists
      were most familiar with NCCN Evidence Blocks (90%), followed by the AVF (84%),
      ICER value framework (57%), and DrugAbacus (56%). Oncologists rated affordability
      higher (mean rating 3: moderately expensive) versus the actual NCCN panel
      affordability rating (mean rating 1: very expensive). The affordability rating
      was similar across a variety of hypothetical cancer therapies and tumor types
      (rating: 3). Oncologists estimated the costs for this rating of 3 to range from
      $4,600 to $6,000 per month, which was inconsistent with actual drug costs.
      Oncologists estimated the mean monthly OOP costs for patients with insurance to
      range from $1,260 for a new oral medication to $1,700 for a new infused
      medication. Only 26% of oncologists were comfortable or very comfortable with
      rating costs associated with affordability levels. CONCLUSIONS: Surveyed
      oncologists rated cancer therapies as more affordable (per NCCN Evidence Blocks
      criteria) than NCCN panel ratings. Costs associated with affordability were not
      consistent with actual treatment costs; however, most oncologists were not
      comfortable with rating affordability. Patient OOP costs had the biggest
      influence on affordability ratings; however, physicians overestimated patient OOP
      costs significantly. There is an opportunity to improve the value frameworks,
      especially with regard to affordability assessment. DISCLOSURES: This study was
      funded by Genentech. Shah-Manek is employed by Ipsos Healthcare, a health care
      consulting company that received funding from Genentech to conduct this study.
      DiBonaventura was employed by Ipsos Healthcare at the time of this study. Wong
      and Ravelo are employed by Genentech. Shah-Manek has consulted with Genentech,
      Merck, Alkermes, Avanis, Alnylam, Novo Nordisk, Teva, Lilly, and BMS. This work
      was presented as an oral presentation at the ASCO 2017 Annual Meeting in Chicago,
      Illinois, on June 2-6, 2017.

PMID- 29451079
TI  - Paired associate learning deficits in poor readers: The contribution of
      phonological input and output processes.
AB  - It is well-established that poor readers exhibit deficits in paired associate
      learning (PAL), and there is increasing evidence for a phonological locus of
      these deficits. However, it remains unclear whether poor performance stems from
      difficulties specific to the phonological output system or difficulties that
      affect both phonological input and output processes. Understanding these deficits
      is important not only in the context of PAL but also for informing broader
      theories of typical and atypical reading development. We developed a novel
      paradigm that allowed us to assess PAL in the presence and absence of
      phonological output demands. In total, 14 poor readers and 14 age-matched
      controls were first trained to criterion in verbal-visual PAL before being tested
      in the visual-verbal direction. The results showed that poor readers learned at
      the same rate as controls in verbal-visual PAL, even when the nonword stimuli
      were phonologically confusable. Yet, despite having reached the same criterion as
      controls in verbal-visual PAL, poor readers exhibited robust impairments for
      those same paired associates in visual-verbal PAL. The overall pattern of results
      is most consistent with the conclusion that PAL deficits reflect impairments to
      the phonological output system; however, results that may challenge this
      interpretation are also discussed.

PMID- 29451080
TI  - Relationships between social skills and self-esteem in nurses: a questionnaire
      study.
AB  - BACKGROUND: Our study attempts to evaluate whether nurses' social skills are
      related to their self-concept and self-esteem. METHODS: A descriptive survey
      study was developed to 464 nurses who had worked for a minimum of one year in
      adult or pediatric services. The Rosenberg Self-Esteem Scale (RSE) and the Scale
      of Social Skills (SSS) by Gismero were used to measure nurses' self-esteem and
      social skills, respectively. RESULTS: Evaluation of self-esteem and social skills
      revealed no significant associations between sex and specific nursing speciality,
      (p > .05). Significant differences were observed based on the marital status for
      RSE and SSS Factor 1 (RSE, p = .013; SSS-F1, p = .033). Correlation and
      regression analyses demonstrated a significant correlation between nurse self
      esteem and some social skills factors. CONCLUSION: This study shows that there
      exists a relationship between higher self-esteem and self-concept among nurses
      and this issue can affect effective communication with patients.

PMID- 29451082
TI  - The Short-Term Placebo Response in Children With Attention-Deficit Hyperactivity
      Disorder (ADHD).
AB  - To assess short-term placebo response in 6- to 13-year-old children with ADHD,
      children who were administered a double-blind placebo-methylphenidate trial, 1
      week each, were included in the analysis. Conners' parents and Teacher Rating
      scales, the Aggregate Neurobehavioral Student Health and Educational Review
      inventory, and the Matching Familiar Figure Test were employed. A reduction of
      30% or more in one or more of the teachers report subscales was observed in 18.8%
      of the participants. Attention test performance resulted in 58% of children
      exhibiting reduction in error rates and 36.2% exhibited longer latency period.
      Significant correlations between placebo response and methylphenidate response in
      all of the teachers report subscales were found. Base line severity, learning
      problem and emotional status were found associated with placebo response. Short
      term placebo response should be accounted for in children with ADHD.

PMID- 29451081
TI  - Permethrin treated clothing to protect outdoor workers: evaluation of different
      methods for mosquito exposure against populations with differing resistance
      status.
AB  - Minimizing arthropod exposure (e.g. mosquito and tick bites) is vital to protect
      health of outdoor workers. Personal protective measures can help protect against
      exposure. Here, the quantity of permethrin was evaluated for different fabric
      types after washing. Cone and petri dish exposure assays were used to investigate
      the knockdown/mortality of permethrin-susceptible and permethrin-resistant
      populations of mosquitoes. Permethrin-treated clothing was effective against the
      tested mosquito population that was susceptible to permethrin but not a
      permethrin-resistant population. Permethrin quantity was significantly highest in
      the 100% cotton fabric and for the 0 wash group. Permethrin quantity in fabrics
      decreased with washing. No significant differences (p > 0.05) were observed in
      knockdown/mortality rates for either exposure method. The protective effect of
      permethrin-treated clothing against mosquitoes is impacted by many factors, e.g.
      wash frequency, fabric type, and the susceptibility/resistance status of local
      mosquito populations.

PMID- 29451084
TI  - Unusual case of choking due to assassin bug ( Cydnocoris gilvus).
AB  - Choking is a form of asphyxia which is caused by an obstruction within the air
      passages. Here, we report a case of obstruction of the upper respiratory tract
      due to assassin bug ( Cydnocoris gilvus) where allegations of medical negligence
      were made by relatives of the deceased. Autopsy findings demonstrated that an
      insect was present inside the larynx, lodged at the epiglottis. Multiple
      haemorrhagic patches were present at the base of the tongue, larynx, epiglottis,
      vocal cords and tracheal bifurcation. As Reduviidae can be successfully used as a
      biological pest-control agents, they should be used with due precaution.

PMID- 29451086
TI  - Efficient robust doubly adaptive regularized regression with applications.
AB  - We consider the problem of estimation and variable selection for general linear
      regression models. Regularized regression procedures have been widely used for
      variable selection, but most existing methods perform poorly in the presence of
      outliers. We construct a new penalized procedure that simultaneously attains full
      efficiency and maximum robustness. Furthermore, the proposed procedure satisfies
      the oracle properties. The new procedure is designed to achieve sparse and robust
      solutions by imposing adaptive weights on both the decision loss and the penalty
      function. The proposed method of estimation and variable selection attains full
      efficiency when the model is correct and, at the same time, achieves maximum
      robustness when outliers are present. We examine the robustness properties using
      the finite-sample breakdown point and an influence function. We show that the
      proposed estimator attains the maximum breakdown point. Furthermore, there is no
      loss in efficiency when there are no outliers or the error distribution is
      normal. For practical implementation of the proposed method, we present a
      computational algorithm. We examine the finite-sample and robustness properties
      using Monte Carlo studies. Two datasets are also analyzed.

PMID- 29451087
TI  - Multiple imputation with sequential penalized regression.
AB  - Missing data is a common issue that can cause problems in estimation and
      inference in biomedical, epidemiological and social research. Multiple imputation
      is an increasingly popular approach for handling missing data. In case of a large
      number of covariates with missing data, existing multiple imputation software
      packages may not work properly and often produce errors. We propose a multiple
      imputation algorithm called mispr based on sequential penalized regression
      models. Each variable with missing values is assumed to have a different
      distributional form and is imputed with its own imputation model using the ridge
      penalty. In the case of a large number of predictors with respect to the sample
      size, the use of a quadratic penalty guarantees unique estimates for the
      parameters and leads to better predictions than the usual Maximum Likelihood
      Estimation (MLE), with a good compromise between bias and variance. As a result,
      the proposed algorithm performs well and provides imputed values that are better
      even for a large number of covariates with small samples. The results are
      compared with the existing software packages mice, VIM and Amelia in simulation
      studies. The missing at random mechanism was the main assumption in the
      simulation study. The imputation performance of the proposed algorithm is
      evaluated with mean squared imputation error and mean absolute imputation error.
      The mean squared error ([Formula: see text]), parameter estimates with their
      standard errors and confidence intervals are also computed to compare the
      performance in the regression context. The proposed algorithm is observed to be a
      good competitor to the existing algorithms, with smaller mean squared imputation
      error, mean absolute imputation error and mean squared error. The algorithm's
      performance becomes considerably better than that of the existing algorithms with
      increasing number of covariates, especially when the number of predictors is
      close to or even greater than the sample size. Two real-life datasets are also
      used to examine the performance of the proposed algorithm using simulations.

PMID- 29451088
TI  - A marginalized two-part model with heterogeneous variance for semicontinuous
      data.
AB  - Semicontinuous data, characterized by a point mass at zero followed by a
      positive, continuous distribution, arise frequently in medical research. These
      data are typically analyzed using two-part mixtures that separately model the
      probability of incurring a positive outcome and the distribution of positive
      values among those who incur them. In such a conditional specification, however,
      standard two-part models do not provide a marginal interpretation of covariate
      effects on the overall population. We have previously proposed a marginalized two
      part model that yields more interpretable effect estimates by parameterizing the
      model in terms of the marginal mean. In the original formulation, a constant
      variance was assumed for the positive values. We now extend this model to a more
      general framework by allowing non-constant variance to be explicitly modeled as a
      function of covariates, and incorporate this variance into two flexible
      distributional assumptions, log-skew-normal and generalized gamma, both of which
      take the log-normal distribution as a special case. Using simulation studies, we
      compare the performance of each of these models with respect to bias, coverage,
      and efficiency. We illustrate the proposed modeling framework by evaluating the
      effect of a behavioral weight loss intervention on health care expenditures in
      the Veterans Affairs health system.

PMID- 29451089
TI  - Randomization-based inference for Bernoulli trial experiments and implications
      for observational studies.
AB  - We present a randomization-based inferential framework for experiments
      characterized by a strongly ignorable assignment mechanism where units have
      independent probabilities of receiving treatment. Previous works on randomization
      tests often assume these probabilities are equal within blocks of units. We
      consider the general case where they differ across units and show how to perform
      randomization tests and obtain point estimates and confidence intervals.
      Furthermore, we develop rejection-sampling and importance-sampling approaches for
      conducting randomization-based inference conditional on any statistic of
      interest, such as the number of treated units or forms of covariate balance. We
      establish that our randomization tests are valid tests, and through simulation we
      demonstrate how the rejection-sampling and importance-sampling approaches can
      yield powerful randomization tests and thus precise inference. Our work also has
      implications for observational studies, which commonly assume a strongly
      ignorable assignment mechanism. Most methodologies for observational studies make
      additional modeling or asymptotic assumptions, while our framework only assumes
      the strongly ignorable assignment mechanism, and thus can be considered a minimal
      assumption approach.

PMID- 29451090
TI  - Study of changes in lipid profile and insulin resistance in Egyptian patients
      with chronic hepatitis C genotype 4 in the era of DAAs.
AB  - Chronic hepatitis C virus (HCV) infection is associated with altered metabolism,
      including dyslipidemia and insulin resistance. These contribute to disease
      progression and influences the response to therapy. To investigate the
      relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with
      lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4
      patients were included; they were divided into four groups according to the
      severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered
      as a control group. Lipid profile changes and IR were analyzed at baseline and
      after the end of treatment, and any effect of these changes on the response to
      treatment was studied. Before treatment, the levels of serum triglycerides were
      significantly higher in patients than in the control, and the levels of fasting
      insulin showed a progressive increase with advancing stage of fibrosis. At the
      end of treatment, there were a significant reduction in serum triglycerides, FBS,
      fasting insulin, and homeostasis model for the assessment of IR (P < 0.001), and
      a significant elevation of serum cholesterol and low-density lipoprotein (LDL)-c,
      high-density lipoprotein (HDL)-c, and LDL/HDL ratio (P = 0.001). An end-of
      treatment response (week 12) was achieved in (99%) of the treated cases with 99%
      sustained viral response for 12 weeks post-treatment (week 24). Significant lipid
      profile changes were detected at the end of treatment. Serum lipid levels and IR
      are no longer predictors of response to DAAs. Follow-up of the lipid profile is
      warranted to avoid any possible remote effect of atherosclerotic heart disease.

PMID- 29451091
TI  - Comparing the effects of education using telephone follow-up and smartphone-based
      social networking follow-up on self-management behaviors among patients with
      hypertension.
AB  - BACKGROUND: Little is known about the benefits of social networks in the
      management of patients. OBJECTIVE: The aim of this study was to compare the
      effects of self-management (SM) education using telephone follow-up and mobile
      phone-based social networking on SM behaviors among patients with hypertension.
      METHODS: This randomized clinical trial was conducted with 100 patients. They
      were randomly allocated to four groups: (i) control, (ii) SM training without
      follow-up, (iii) telephone follow-up and (iv) smartphone-based social networking
      follow-up. The hypertension SM behavior questionnaire was used for data
      collection before and six weeks after the study. RESULTS: Those patients who
      underwent SM education training (with and without follow-up) had statistically
      significant differences from those in the control group in terms of SM behaviors
      (p < .001). There was no statistically significant difference between different
      types of follow-up. CONCLUSION: SM education using telephone follow-up and/or
      smartphone-based social networking follow-up influenced SM behaviors among
      patients with hypertension.

PMID- 29451092
TI  - Driving comfort, enjoyment and acceptance of automated driving - effects of
      drivers' age and driving style familiarity.
AB  - Automated driving has the potential to improve the safety and efficiency of
      future traffic and to extend elderly peoples' driving life, provided it is
      perceived as comfortable and joyful and is accepted by drivers. Driving comfort
      could be enhanced by familiar automated driving styles based on drivers' manual
      driving styles. In a two-stage driving simulator study, effects of driving
      automation and driving style familiarity on driving comfort, enjoyment and system
      acceptance were examined. Twenty younger and 20 older drivers performed a manual
      and four automated drives of different driving style familiarity. Acceptance,
      comfort and enjoyment were assessed after driving with standardised
      questionnaires, discomfort during driving via handset control. Automation
      increased both age groups' comfort, but decreased younger drivers' enjoyment.
      Younger drivers showed higher comfort, enjoyment and acceptance with familiar
      automated driving styles, whereas older drivers preferred unfamiliar, automated
      driving styles tending to be faster than their age-affected manual driving
      styles. Practitioner Summary: Automated driving needs to be comfortable and
      enjoyable to be accepted by drivers, which could be enhanced by driving style
      individualisation. This approach was evaluated in a two-stage driving simulator
      study for different age groups. Younger drivers preferred familiar driving
      styles, whereas older drivers preferred driving styles unaffected by age.

PMID- 29451094
TI  - Growth and optimization of carbon nanotubes in powder activated carbon for an
      efficient removal of methylene blue from aqueous solution.
AB  - This work demonstrated the synthesis of carbon nanotubes (CNTs) on powder
      activated carbon (PAC) impregnated with Ni-catalyst through chemical vapour
      deposition. The optimized effects of reaction temperature, time and feedstock
      flow rates on CNT growth were examined. Potassium permanganate (KMnO4) and
      potassium permanganate in acidic solution (KMnO4/H2SO4) were used to
      functionalize CNTs samples. A primary screening of methylene blue (MB) adsorption
      was conducted. The chemical, physical and morphological properties of the
      adsorbent with the highest removal efficiency were investigated using FESEM, EDX,
      TEM, BET surface area, RAMAN, TGA, FTIR, and zeta potential. The resulting carbon
      nanotube-loaded activated carbons possessed abundant pore structure and large
      surface area. The MB removal by the as-synthesized CNTs was more remarkable than
      that by the modified samples. Adsorption studies were carried out to evaluate the
      optimum conditions, kinetics and isotherms for MB adsorption process. The
      response surface methodology-central composite design (RSM-CCD) was used to
      optimize the adsorption process parameters, including pH, adsorbent dosage and
      contact time. The investigation of the adsorption behaviour demonstrated that the
      adsorption was well fitted with the pseudo-second-order model and Langmuir
      isotherm with the maximum monolayer adsorption capacity of 174.5 mg/g. Meanwhile,
      the adsorption of MB onto adsorbent was driven by the electrostatic attraction
      and pi-pi interaction. Moreover, the as-obtained CNT-PAC exhibited good
      reusability after four repeated operations. In view of these empirical findings,
      the low-cost CNT-PAC has potential for removal of MB from aqueous solution.

PMID- 29451093
TI  - Adjustment for time-invariant and time-varying confounders in 'unexplained
      residuals' models for longitudinal data within a causal framework and associated
      challenges.
AB  - 'Unexplained residuals' models have been used within lifecourse epidemiology to
      model an exposure measured longitudinally at several time points in relation to a
      distal outcome. It has been claimed that these models have several advantages,
      including: the ability to estimate multiple total causal effects in a single
      model, and additional insight into the effect on the outcome of greater-than
      expected increases in the exposure compared to traditional regression methods. We
      evaluate these properties and prove mathematically how adjustment for confounding
      variables must be made within this modelling framework. Importantly, we
      explicitly place unexplained residual models in a causal framework using directed
      acyclic graphs. This allows for theoretical justification of appropriate
      confounder adjustment and provides a framework for extending our results to more
      complex scenarios than those examined in this paper. We also discuss several
      interpretational issues relating to unexplained residual models within a causal
      framework. We argue that unexplained residual models offer no additional insights
      compared to traditional regression methods, and, in fact, are more challenging to
      implement; moreover, they artificially reduce estimated standard errors.
      Consequently, we conclude that unexplained residual models, if used, must be
      implemented with great care.

PMID- 29451095
TI  - A tale of two campuses: Lessons learned in establishing a satellite campus.
AB  - "It was the best of times, it was the worst of times, it was the age of wisdom,
      it was the age of foolishness, it was the epoch of belief, it was the epoch of
      incredulity." The opening line of Dickens's A Tale of Two Cities could easily be
      the dramatic opening line of a summary of the establishment of a satellite
      medical school campus in Manitoba. Reflection on my last four years as associate
      dean reveals that most of the descriptors in that famous sentence at one time or
      another were apropos. This brief essay will relate the experiences of the last
      four years and some of the lessons learned along the way.

PMID- 29451096
TI  - Elevated CRP at admission predicts post-stroke cognitive impairment in Han
      Chinese patients with intracranial arterial stenosis.
AB  - OBJECTIVES: Elevated C-reactive protein (CRP) levels have been associated with
      cognitive deficits in certain patient populations, but whether this is also true
      of ischemic stroke patients is controversial. This study aims to examine the
      possible association between CRP concentration and post-stroke cognitive
      impairment (PSCI) in Han Chinese patients and to determine whether this
      association depends on intracranial arterial stenosis (ICAS). METHODS: Patients
      with mild or moderate stroke admitted to a large regional medical center in
      Western China were consecutively enrolled in our study. Serum levels of CRP and
      ICAS severity were assessed at admission and cognitive status was assessed 6
      months after stroke using the Six-Item Screener. RESULTS: Of the 1116 patients
      included in our study, no association was observed between CRP levels at
      admission and cognitive performance at 6 months. However, among the subgroup of
      311 patients with ICAS, a significant association did exist, and it persisted
      even after adjusting for potential confounders (OR 1.038, 95% CI 1.015-1.061). We
      did not find the same association in the subgroup of the patients without ICAS.
      CONCLUSIONS: To our knowledge, this is the first study to explore the effects of
      CRP on PSCI in Han Chinese with ICAS. Our findings indicate that higher CRP
      levels at admission are associated with subsequent cognitive decline in Han
      Chinese patients with ICAS following ischemic stroke. Further studies in other
      ethnic groups are needed to validate the use of CRP to predict dementia in ICAS
      patients.

PMID- 29451097
TI  - A three-dimensional printed patient-specific scaphoid replacement: a cadaveric
      study.
AB  - We present our first cadaveric test results of a three-dimensional printed
      patient-specific scaphoid replacement with tendon suspension, which showed normal
      motion behaviour and preservation of a stable scapholunate interval during
      physiological range of motion.

PMID- 29451098
TI  - The association between preaxial polydactyly and radial longitudinal deficiency
      in syndromic cases: a report on nine families.
AB  - : Preaxial polydactyly and radial longitudinal deficiency are usually viewed as
      two different entities. We present nine families with different disorders in
      which both preaxial polydactyly and radial longitudinal deficiency were seen in
      the phenotype. This indicates that both entities may be caused by the same
      developmental error or insult. The pathogenesis is complex and may be related to
      the interactions of two signalling loops: the first loop (named as the radial
      longitudinal deficiency loop) contains genes/proteins responsible for the
      development of the radial ray; and the second loop (named as the preaxial
      polydactyly loop) contains the Sonic Hedgehog involved in the pathogenesis of
      preaxial polydactyly. This entity is named as the preaxial polydactyly-radial
      longitudinal deficiency association and should be included in the description of
      the preaxial polydactyly spectrum. LEVEL OF EVIDENCE: IV.

PMID- 29451099
TI  - A systematic review and meta-analysis of arthroscopic assisted techniques for
      thumb carpometacarpal joint osteoarthritis.
AB  - Arthroscopic management of thumb carpometacarpal (CMC) osteoarthrosis (OA) is an
      approach that has unclear results. We performed a systematic review encompassing
      three electronic databases up to May 2016 for studies describing arthroscopic
      assisted techniques for thumb CMC OA. Meta-analyses of visual analogue scores
      (VAS) for pain, Disabilities of the Arm, Shoulder and Hand (DASH) scores, grip
      strength and pinch strength before and after arthroscopy were performed for ten
      included non-randomized cohort studies comprising 294 patients. Based on Hedges'
      g measure, we found a large effect on VAS and DASH scores, a small effect on grip
      strength and no effect on pinch strength. On average, VAS improved by 4.1 cm,
      DASH by 22 points and grip strength by 2.8 kg. Complications were reported in 4%
      of patients. The use of arthroscopic-assisted techniques for thumb CMC OA is
      still limited; however, it may be a reasonable option for patients with thumb CMC
      OA who do not respond to non-operative treatment.

PMID- 29451100
TI  - Ethnographic analysis of communication and the deaf community's rights in the
      clinical context.
AB  - BACKGROUND: Communication is a key factor in the health system. In the case of
      Deaf Community healthcare interactions could be affected by communication and it
      can also have a negative impact on health and jeopardise some of their health
      rights. OBJECTIVES: Aims (i) know the communication access difficulties of deaf
      people in healthcare context (ii) determine how these difficulties violate their
      rights. METHODS: Ethnographical study. RESULTS: Subjects were 25 deaf adults (7
      men; 18 women). Two themes were identified (1) barriers to information access -
      right to information; (2) communication barriers - right to privacy and to
      decide. CONCLUSIONS: Communication difficulties and access to information have an
      impact on the health of deaf people, and violate health rights. In addition,
      their language rights like a community are also violate. Impact statement:
      Research could have a positive impact on improvement to access, communication and
      safe in the Deaf Community, in a clinical context.

PMID- 29451101
TI  - Severe tricuspid regurgitation and seizure on postpartum day 10: case report of
      late postpartum eclampsia.
AB  - OBJECTIVE AND IMPORTANCE: Late postpartum eclampsia is characterized by pre
      eclampsia and tonic-clonic seizures presenting more than 48 hours postpartum. It
      is a rare, frightening and dangerous complication that requires rapid recognition
      and adequate treatment. CLINICAL PRESENTATION: We present a case of late
      postpartum eclampsia, initially diagnosed as right-sided heart failure, 10 days
      postpartum.Two days after the delivery she developed mild swelling of both feet,
      progressive shortness of breath on exertion and orthopnea. INTERVENTION:
      Transthoracic echocardiography revealed sever tricuspid regurgitation in
      combination with pulmonary hypertension. The patient wasadmitted to the intensive
      care unit (ICU) and a tentative diagnosis of pulmonary hypertension was made. On
      arrival in the ICU, the patient developed a tonic-clonic seizure and urinalysis
      revealed proteinuria, indicating eclampsia. Treatment of eclampsia was initiated
      with complete resolution of symptoms. CONCLUSION: This caseemphasizes the
      importance of considering late postpartum eclampsia in patients presenting with
      signs of pulmonary edema even several days after delivery, as early diagnosis and
      prompt initiation of appropriate antihypertensive and anticonvulsant therapy can
      prevent severe complications.

PMID- 29451102
TI  - Single ablative intravesical electromotive mitomycin C administration for small
      non-muscle-invasive bladder cancer: a prospective study.
AB  - Objectives To explore the effect of electromotive drug administration of
      mitomycin C (EMDA-MMC) using a single dose of intravesical mitomycin C (MMC) to
      avoid transurethral resection (TURBT) for small non-muscle-invasive bladder
      cancer. Material and methods All patients presenting small (<2 cm), single or
      multiple papillary bladder tumors were proposed to undergo a single EMDA-MMC
      instillation with 60 mg MMC before planning TURBT. The end point is complete
      disappearance of all papillary tumors at 2-4 weeks after EMDA-MMC. Results Thirty
      six instillations were given to 32 patients. In general the treatment was well
      supported, except for two patients who had severe bladder spasms, resulting in
      early evacuation of the MMC. Complete response occurred in 28% (10/36
      instillations). In 4 EMDA-MMCs with multiple tumors some tumors disappeared while
      others remained. In 61% (22/36) the tumors remained unchanged. Conclusion A
      single EMDA-MMC in l papillary bladder tumors <2 cm gives insufficient ablative
      effect.

PMID- 29451103
TI  - Effects of combustion temperature on air emissions and support fuel consumption
      in full scale fluidized bed sludge incineration: with particular focus on
      nitrogen oxides and total organic carbon.
AB  - This article describes a pilot test at a sewage sludge incineration plant and
      shows its results considering the impacts of reducing the minimum combustion
      temperature from 850 degrees C to 800 degrees C. The lowering leads to an actual
      reduction of the average combustion temperature by 25 K and a significant
      reduction in the fuel oil consumption for support firing. The test shall be used
      for providing evidence that the changed combustion conditions do not result in
      higher air pollutant emissions. The analysis focusses on the effects of the
      combustion temperature on nitrogen oxides (NOx) and total organic carbon
      emissions. The evaluation of all continuously monitored emissions shows reduced
      emission levels compared to the previous years, especially for NOx.

PMID- 29451104
TI  - A multi-criteria decision-making approach to rank supplier selection criteria for
      hospital waste management: A case from Pakistan.
AB  - To address environmental issues and cost effectiveness, waste management is
      necessary for healthcare facilities. Most importantly, segregation of hazardous
      and non-hazardous waste must be done as in many developing countries; disposal of
      both types of healthcare waste is done together, which is an unsafe practice.
      Waste generated in hospitals needs proper management to minimise hazards for
      patient and healthcare workers. At the same time, it is quite difficult for
      hospitals to find a systematic way to select appropriate suppliers for hospital
      waste management. Therefore, the purpose of this article is to identify,
      validate, and rank criteria that are essential for hospital waste management
      suppliers' selection. The analytical hierarchal process approach has been used
      and a survey from Pakistan's largest city (Karachi) has been considered to rank
      the most appropriate criteria that is necessary to select the supplier,
      especially in a developing country like Pakistan. Results show that waste
      management cost (45.5%) and suppliers' details (31.5%) are the top two main
      criteria for supplier selection; and storage cost (15.7%), waste handling cost
      (14.7%), and qualification of the suppliers (10.9%) are the top three most
      important overall sub-criteria for supplier selection for hospital waste
      management.

PMID- 29451106
TI  - Thinking in a Foreign language reduces the causality bias.
AB  - The purpose of this research is to investigate the impact of a foreign language
      on the causality bias (i.e., the illusion that two events are causally related
      when they are not). We predict that using a foreign language could reduce the
      illusions of causality. A total of 36 native English speakers participated in
      Experiment 1, 80 native Spanish speakers in Experiment 2. They performed a
      standard contingency learning task, which can be used to detect causal illusions.
      Participants who performed the task in their native tongue replicated the
      illusion of causality effect, whereas those performing the task in their foreign
      language were more accurate in detecting that the two events were causally
      unrelated. Our results suggest that presenting the information in a foreign
      language could be used as a strategy to debias individuals against causal
      illusions, thereby facilitating more accurate judgements and decisions in non
      contingent situations. They also contribute to the debate on the nature and
      underlying mechanisms of the foreign language effect, given that the illusion of
      causality is rooted in basic associative processes.

PMID- 29451105
TI  - Human-automation interaction for multiple robot control: the effect of varying
      automation assistance and individual differences on operator performance.
AB  - In a human-automation interaction study, automation assistance level (AL) was
      investigated for its effects on operator performance in a dynamic, multi-tasking
      environment. Participants supervised a convoy of manned and unmanned vehicles
      traversing a simulated environment in three AL conditions, while maintaining
      situation awareness and identifying targets. Operators' situation awareness,
      target detection performance, workload and individual differences were evaluated.
      Results show increasing AL generally improved task performance and decreased
      perceived workload, however, differential effects due to operator spatial ability
      and perceived attentional control were found. Eye-tracking measures were useful
      in parsing out individual differences that subjective measures did not detect. At
      the highest AL, participants demonstrated potentially complacent behaviour,
      indicating task disengagement. Practitioner Summary: The effect of varying
      automation assistance level (AL) on operator performance on multiple tasks were
      examined in a within-subjects experiment. Findings indicated a moderate AL
      improved performance, while higher levels encouraged complacent behaviour.
      Effects due to individual differences suggest that effective AL depends on the
      underlying characteristics of the operator.

PMID- 29451108
TI  - Editorial: Smart Drug Delivery Systems (Part 1).

PMID- 29451107
TI  - Bilaterally Combined Electric and Acoustic Hearing in Mandarin-Speaking
      Listeners: The Population With Poor Residual Hearing.
AB  - The hearing loss criterion for cochlear implant candidacy in mainland China is
      extremely stringent (bilateral severe to profound hearing loss), resulting in few
      patients with substantial residual hearing in the nonimplanted ear. The main
      objective of the current study was to examine the benefit of bimodal hearing in
      typical Mandarin-speaking implant users who have poorer residual hearing in the
      nonimplanted ear relative to those used in the English-speaking studies.
      Seventeen Mandarin-speaking bimodal users with pure-tone averages of ~80 dB HL
      participated in the study. Sentence recognition in quiet and in noise as well as
      tone and word recognition in quiet were measured in monaural and bilateral
      conditions. There was no significant bimodal effect for word and sentence
      recognition in quiet. Small bimodal effects were observed for sentence
      recognition in noise (6%) and tone recognition (4%). The magnitude of both
      effects was correlated with unaided thresholds at frequencies near voice
      fundamental frequencies (F0s). A weak correlation between the bimodal effect for
      word recognition and unaided thresholds at frequencies higher than F0s was
      identified. These results were consistent with previous findings that showed more
      robust bimodal benefits for speech recognition tasks that require higher spectral
      resolution than speech recognition in quiet. The significant but small F0-related
      bimodal benefit was also consistent with the limited acoustic hearing in the
      nonimplanted ear of the current subject sample, who are representative of the
      bimodal users in mainland China. These results advocate for a more relaxed
      implant candidacy criterion to be used in mainland China.

PMID- 29451109
TI  - [Orthostatic hypotension in elderly patients].
AB  - - Orthostatic hypotension is a condition in which there is insufficient recovery
      of the blood pressure drop which occurs after getting up, which causes a
      temporary reduction of cerebral perfusion. This increases the risk of falls
      resulting in injuries.- Orthostatic hypotension is most common in the elderly.
      The cause is usually multifactorial (including reduced circulating volume,
      reduced peripheral resistance and limited heart rate increase). Orthostatic
      hypotension caused by autonomic dysfunction is called neurogenic orthostatic
      hypotension.- The most important groups of drugs that may elicit orthostatic
      hypotension are: diuretics (but only if they lead to hypovolaemia),
      antidepressants (mainly tricyclic antidepressants), sympatholytics (alpha
      blockers as well as beta-blockers) and vasodilators (for example, nitrates).-
      Treatment of the elderly with orthostatic hypotension starts with lifestyle
      advice (getting up slowly) and possible medication adjustments.

PMID- 29451110
TI  - [Risk of heart failure diminished thanks to stomach reduction in obesity].
AB  - BACKGROUND: Obesity is a chronic disease and a risk factor for heart failure. In
      end-stage heart failure, heart transplantation may be the only available
      treatment option, but obesity is a contraindication for this treatment because of
      its unfavourable prognosis. Bariatric surgery and its subsequent weight loss may
      affect the indication for transplantation in patients with heart failure and
      morbid obesity. CASE DESCRIPTION: A 46-year-old patient with morbid obesity and
      heart failure underwent gastric sleeve resection in preparation of a heart
      transplantation. Without it, he would not have been considered eligible for
      transplantation because of his obesity. The bariatric intervention was also
      intended to use weight loss as a way to reduce the symptoms of his heart failure
      and to make rehabilitation possible. One year after surgery, the condition of the
      patient had improved so much that heart transplantation was no longer necessary.
      CONCLUSION: Bariatric surgery is safe for morbidly obese patients with severe
      heart failure and may sometimes even avoid heart transplantation.

PMID- 29451111
TI  - [In- and out-of-hospital emergency psychiatry: what is the best approach?]
AB  - A range of clinical syndromes may present with psychiatric symptoms, both in and
      out of hospital settings. In such situations agitation, suicidality,
      communication difficulties and legal aspects often play a role, making diagnosis
      and treatment a challenge. Based on several case studies, we illustrate how the
      recently-published Dutch open access source 'Acute Psychiatry'
      (www.acutepsychiatrie.com) can be of help in acute psychiatric presentations both
      within and outside psychiatric hospitals.

PMID- 29451112
TI  - [Regained freedom for patients with atopic dermatitis; fast and long-term effects
      of dupilumab].
AB  - Dupilumab is the first and long-awaited biological for treatment of moderate to
      severe atopic dermatitis. In randomised clinical trials approximately 40% of
      patients using dupilumab 300 mg every two weeks were clear or almost clear of
      their eczema after 16 and 52 weeks. We now face the challenge of patient
      stratification to limit the budget impact of dupilumab and hope that more
      targeted therapies for atopic dermatitis will follow soon.

PMID- 29451113
TI  - [Telephone triage by the general practitioner: not a smart move].
AB  - In the Telephone First approach that has been introduced in the UK, within a few
      hours of patients contacting their GP practice a general practitioner will call
      back all patients who want to make an appointment within a few hours. We think
      that it is not wise to introduce this system in the Netherlands. Research has not
      shown sufficient advantages and the system hampers rethinking the traditional way
      of handling patient requests and the growing workload in general practice.
      Instead, focus should be paid to more diverse and innovative ways of dealing with
      patient demands.

PMID- 29451114
TI  - Molecular Tools To Study Preharvest Food Safety Challenges.
AB  - Preharvest food safety research and activities have advanced over time with the
      recognition of the importance and complicated nature of the preharvest phase of
      food production. In developed nations, implementation of preharvest food safety
      procedures along with strict monitoring and containment at various postharvest
      stages such as slaughter, processing, storage, and distribution have remarkably
      reduced the burden of foodborne pathogens in humans. Early detection and adequate
      surveillance of pathogens at the preharvest stage is of the utmost importance to
      ensure a safe meat supply. There is an urgent need to develop rapid, cost
      effective, and point-of-care diagnostics which could be used at the preharvest
      stage and would complement postmortem and other quality checks performed at the
      postharvest stage. With newer methods and technologies, more efforts need to be
      directed toward developing rapid, sensitive, and specific methods for detection
      or screening of foodborne pathogens at the preharvest stage. In this review, we
      will discuss the molecular methods available for detection and molecular typing
      of bacterial foodborne pathogens at the farm. Such methods include conventional
      techniques such as endpoint PCR, real-time PCR, DNA microarray, and more advanced
      techniques such as matrix-assisted layer desorption ionization-time of flight
      mass spectrometry and whole-genome sequencing.

PMID- 29451115
TI  - Understanding the Complexities of Food Safety Using a "One Health" Approach.
AB  - The philosophy of One Health is growing in concept and clarity. The
      interdependence of human, animal, and environmental health is the basis for the
      concept of One Health. One Health is a comprehensive approach to ensure the
      health of people, animals, and the environment through collaborative efforts.
      Preharvest food safety issues align with the grand concept of One Health. Imagine
      any food production system, and immediately, parallel images from One Health
      emerge: for example, transmission of zoonotic diseases, antibiotic residues, or
      resistance genes in the environment; environmental and animal host reservoirs of
      disease; challenges with rearing animals and growing fresh produce on the same
      farm; application and transport of manure or diseased animals. During a recent
      celebration of #OneHealthDay, information was shared around the globe concerning
      scientists dedicated to One Health research systems. An ever-growing trade and
      global commerce system mixed with our incessant desire for food products during
      the whole year makes it all the more important to take a global view through the
      One Health lens to solve these growing challenges. The recent explosion of Zika
      virus around the globe renewed the need for assessing transmissible diseases
      through the eyes of One Health. It is not good enough to know how a disease
      affects the human population without a thorough understanding of the environment
      and vector reservoirs. If 60 to 75% of infectious diseases affecting humans are
      of animal origin, the need for better One Health research strategies and overdue
      solutions is imperative.

PMID- 29451116
TI  - Population-Tailored Care for Homeless Veterans and Acute Care Use, Cost, and
      Satisfaction: A Prospective Quasi-Experimental Trial.
AB  - INTRODUCTION: Although traditional patient-centered medical homes (PCMHs) are
      effective for patients with complex needs, it is unclear whether homeless
      tailored PCMHs work better for homeless veterans. We examined the impact of
      enrollment in a Veterans Health Administration (VHA) homeless-tailored PCMH on
      health services use, cost, and satisfaction compared with enrollment in a
      traditional, nontailored PCMH. METHODS: We conducted a prospective, multicenter,
      quasi-experimental, single-blinded study at 2 VHA medical centers to assess
      health services use, cost, and satisfaction during 12 months among 2 groups of
      homeless veterans: 1) veterans receiving VHA homeless-tailored primary care
      (Homeless-Patient Aligned Care Team [H-PACT]) and 2) veterans receiving
      traditional primary care services (PACT). A cohort of 266 homeless veterans
      enrolled from June 2012 through January 2014. RESULTS: Compared with PACT
      patients, H-PACT patients had more social work visits (4.6 vs 2.7 visits) and
      fewer emergency department (ED) visits for ambulatory care-sensitive conditions
      (0 vs 0.2 visits); a significantly smaller percentage of veterans in H-PACT were
      hospitalized (23.1% vs 35.4%) or had mental health-related ED visits (34.1% vs
      47.6%). We found significant differences in primary care provider-specific visits
      (H-PACT, 5.1 vs PACT, 3.6 visits), mental health care visits (H-PACT, 8.8 vs
      PACT, 13.4 visits), 30-day prescription drug fills (H-PACT, 40.5 vs PACT, 58.8
      fills), and use of group therapy (H-PACT, 40.1% vs PACT, 53.7%). Annual costs per
      patient were significantly higher in the PACT group than the H-PACT group
      ($37,415 vs $28,036). In logistic regression model of acute care use, assignment
      to the H-PACT model was protective as was rating health "good" or better.
      CONCLUSION: Homeless veterans enrolled in the population-tailored primary care
      approach used less acute care and costs were lower. Tailored-care models have
      implications for care coordination in the US Department of Veterans Affairs VA
      and community health systems.

PMID- 29451117
TI  - Improving the Food Environment in Hospitals and Senior Meal Programs.
AB  - Most Americans consume more than the recommended daily level of sodium, and tools
      are needed to assess and improve food practices related to sodium. We describe
      how the Sodium Practices Assessment Tool (SPAT) was developed and used in 19
      hospitals and senior meal facilities in upstate New York. Initial results
      identified opportunities for improvement in food preparation, presentation, and
      purchasing practices to reduce sodium consumption. Pre-post comparison results
      showed significant increases in the use of herbs, spices, unsalted butter, fruits
      and vegetables, and in the availability of lower-sodium foods. Food service sites
      can use SPAT to assess sodium practices, inform development of action plans, and
      measure change over time.

PMID- 29451119
TI  - Light triggered interfacial damage self-healing of poly(p-phenylene
      benzobisoxazole) fiber composites.
AB  - The interfacial microcracks in the resin matrix composites are difficult to be
      detected and repaired. However, the self-healing concept provides opportunities
      to fabricate composites with unusual properties. In the present study,
      photothermal conversion Ag-Cu2S nanoparticles were immobilized onto poly(p
      phenylene benzobisoxazole) (PBO) fibers via a polydopamine chemistry. Benefitting
      from the photothermal effects of Ag-Cu2S, the obtained PBO fibers (Ag-Cu2S-PBO)
      efficiently converted the light energy into heat under Xenon lamp irradiation.
      Then, single PBO fiber composites were prepared using thermoplastic polyurethane
      as the matrix. It was found that the interfacial damage caused by single fiber
      pull-out was simply self-healed by Xe light irradiation. This wonderful
      interfacial damage self-healing property was mainly attributed to the in situ
      heating generation via photothermal effects of Ag-Cu2S in the composite
      interface. This paper reports a novel strategy to construct advanced composites
      with light-triggered self-healing properties, which will provide inspiration for
      preparing high performance composite materials.

PMID- 29451118
TI  - A spatial memory signal shows that the parietal cortex has access to a
      craniotopic representation of space.
AB  - Humans effortlessly establish a gist-like memory of their environment whenever
      they enter a new place, a memory that can guide action even in the absence of
      vision. Neurons in the lateral intraparietal area (LIP) of the monkey exhibit a
      form of this environmental memory. These neurons respond when a monkey makes a
      saccade that brings the spatial location of a stimulus that appeared on a number
      of prior trials, but not on the present trial, into their receptive fields (RFs).
      The stimulus need never have appeared in the neuron's RF. This memory response is
      usually weaker, with a longer latency than the neuron's visual response. We
      suggest that these results demonstrate that LIP has access to a supraretinal
      memory of space, which is activated when the spatial location of the vanished
      stimulus can be described by a retinotopic vector from the center of gaze to the
      remembered spatial location.

PMID- 29451120
TI  - An in silico framework to analyze the anisotropic shear wave mechanics in cardiac
      shear wave elastography.
AB  - Shear wave elastography (SWE) is a potential tool to non-invasively assess
      cardiac muscle stiffness. This study focused on the effect of the orthotropic
      material properties and mechanical loading on the performance of cardiac SWE, as
      it is known that these factors contribute to complex 3D anisotropic shear wave
      propagation. To investigate the specific impact of these complexities, we
      constructed a finite element model with an orthotropic material law subjected to
      different uniaxial stretches to simulate SWE in the stressed cardiac wall. Group
      and phase speed were analyzed in function of tissue thickness and virtual probe
      rotation angle. Tissue stretching increased the group and phase speed of the
      simulated shear wave, especially in the direction of the muscle fiber. As the
      model provided access to the true fiber orientation and material properties, we
      assessed the accuracy of two fiber orientation extraction methods based on SWE.
      We found a higher accuracy (but lower robustness) when extracting fiber
      orientations based on the location of maximal shear wave speed instead of the
      angle of the major axis of the ellipsoidal group speed surface. Both methods had
      a comparable performance for the center region of the cardiac wall, and performed
      less well towards the edges. Lastly, we also assessed the (theoretical) impact of
      pathology on shear wave physics and characterization in the model. It was found
      that SWE was able to detect changes in fiber orientation and material
      characteristics, potentially associated with cardiac pathologies such as
      myocardial fibrosis. Furthermore, the model showed clearly altered shear wave
      patterns for the fibrotic myocardium compared to the healthy myocardium, which
      forms an initial but promising outcome of this modeling study.

PMID- 29451121
TI  - Influences of Au ion radiation on microstructure and surface-enhanced Raman
      scattering of nanoporous copper.
AB  - In this work, effects of Au ion irradiation on microstructure and surface
      enhanced Raman scattering (SERS) performance of nanoporous copper (NPC) were
      investigated. It is found that the microstructure of NPC could be tailored by the
      ion irradiation dose, i.e., the pore size decreases while the ligament size
      significantly coarsens with the increase of the irradiation dose. In addition,
      the SERS enhancement for rhodamine 6G molecules was improved by Au ions
      irradiation at an appropriate dose. The underlying mechanism of the increase of
      SERS enhancement resulted from ion irradiation was discussed. Our findings could
      provide a new way to tune nanoporosity of nanoporous metals and improve their
      SERS performance.

PMID- 29451122
TI  - Sprouting angiogenesis in engineered pseudo islets.
AB  - Despite the recent achievements in cell-based therapies for curing type-1
      diabetes (T1D), capillarization in beta (beta)-cell clusters is still a major
      roadblock as it is essential for long-term viability and function of beta-cells
      in vivo. In this research, we report sprouting angiogenesis in engineered pseudo
      islets (EPIs) made of mouse insulinoma betaTC3 cells and rat heart microvascular
      endothelial cells (RHMVECs). Upon culturing in three-dimensional (3D) constructs
      under angiogenic conditions, EPIs sprouted extensive capillaries into the
      surrounding matrix. Ultra-morphological analysis through histological sections
      also revealed presence of capillarization within EPIs. EPIs cultured in 3D
      constructs maintained their viability and functionality over time while non
      vascularized EPIs, without the presence of RHMVECs, could not retain their
      viability nor functionality. Here we demonstrate angiogenesis in engineered
      islets, where patient specific stem cell-derived human beta cells can be combined
      with microvascular endothelial cells in the near future for long-term graft
      survival in T1D patients.

PMID- 29451123
TI  - Analytical bond order potential for simulations of BeO 1D and 2D nanostructures
      and plasma-surface interactions.
AB  - An analytical interatomic bond order potential for the Be-O system is presented.
      The potential is fitted and compared to a large database of bulk BeO and point
      defect properties obtained using density functional theory. Its main applications
      include simulations of plasma-surface interactions involving oxygen or oxide
      layers on beryllium, as well as simulations of BeO nanotubes and nanosheets. We
      apply the potential in a study of oxygen irradiation of Be surfaces, and observe
      the early stages of an oxide layer forming on the Be surface. Predicted thermal
      and elastic properties of BeO nanotubes and nanosheets are simulated and compared
      with published ab initio data.

PMID- 29451124
TI  - Copper oxide loaded PLGA nanospheres: towards a multifunctional nanoscale
      platform for ultrasound-based imaging and therapy.
AB  - Copper oxide nanoparticles (CuO-NPs) are increasingly becoming the subject of
      investigation exploring their potential use for diagnostic and therapeutic
      purposes. Recent work has demonstrated their anticancer potential, as well as
      contrast agent capabilities for magnetic resonance imaging (MRI) and through
      transmission ultrasound. However, no capability of CuO-NPs has been demonstrated
      using conventional ultrasound systems, which, unlike the former, are widely
      deployed in the clinic. Furthermore, in spite of their potential as
      multifunctional nano-based materials for diagnosis and therapy, CuO-NPs have been
      delayed from further clinical application due to their inherent toxicity. Herein,
      we present the synthesis of a novel nanoscale system, composed of CuO-loaded PLGA
      nanospheres (CuO-PLGA-NS), and demonstrate its imaging detectability and
      augmented heating effect by therapeutic ultrasound. The CuO-PLGA-NS were prepared
      by a double emulsion (W/O/W) method with subsequent solvent evaporation. They
      were characterized as sphere-shaped, with size approximately 200 nm. Preliminary
      results showed that the viability of PANC-1, human pancreatic adenocarcinoma
      cells was not affected after 72 h exposure to CuO-PLGA-NS, implying that PLGA
      masks the toxic effects of CuO-NPs. A systematic ultrasound imaging evaluation of
      CuO-PLGA-NS, using a conventional system, was performed in vitro and ex vivo
      using poultry heart and liver, and also in vivo using mice, all yielding a
      significant contrast enhancement. In contrast to CuO-PLGA-NS, neither bare CuO
      NPs nor blank PLGA-NS possess these unique advantageous ultrasonic properties.
      Furthermore, CuO-PLGA-NS accelerated ultrasound-induced temperature elevation by
      more than 4  degrees C within 2 min. The heating efficiency (cumulative
      equivalent minutes at 43  degrees C) was increased approximately six-fold,
      demonstrating the potential for improved ultrasound ablation. In conclusion, CuO
      PLGA-NS constitute a versatile platform, potentially useful for combined imaging
      and therapeutic ultrasound-based procedures.

PMID- 29451125
TI  - Reduced integration and improved segregation of functional brain networks in
      Alzheimer's disease.
AB  - OBJECTIVE: Emerging evidence shows that cognitive deficits in Alzheimer's disease
      (AD) are associated with disruptions in brain functional connectivity. Thus, the
      identification of alterations in AD functional networks has become a topic of
      increasing interest. However, to what extent AD induces disruption of the balance
      of local and global information processing in the human brain remains elusive.
      The main objective of this study is to explore the dynamic topological changes of
      AD networks in terms of brain network segregation and integration. APPROACH: We
      used electroencephalography (EEG) data recorded from 20 participants (10 AD
      patients and 10 healthy controls) during resting state. Functional brain networks
      were reconstructed using EEG source connectivity computed in different frequency
      bands. Graph theoretical analyses were performed assess differences between both
      groups. MAIN RESULTS: Results revealed that AD networks, compared to networks of
      age-matched healthy controls, are characterized by lower global information
      processing (integration) and higher local information processing (segregation).
      Results showed also significant correlation between the alterations in the AD
      patients' functional brain networks and their cognitive scores. SIGNIFICANCE:
      These findings may contribute to the development of EEG network-based test that
      could strengthen results obtained from currently-used neurophysiological tests in
      neurodegenerative diseases.

PMID- 29451126
TI  - Fabrication of ultrathin multilayered superomniphobic nanocoatings by liquid
      flame spray, atomic layer deposition, and silanization.
AB  - Superomniphobic, i.e. liquid-repellent, surfaces have been an interesting area of
      research during recent years due to their various potential applications.
      However, producing such surfaces, especially on hard and resilient substrates
      like stainless steel, still remains challenging. We present a stepwise
      fabrication process of a multilayered nanocoating on a stainless steel substrate,
      consisting of a nanoparticle layer, a nanofilm, and a layer of silane molecules.
      Liquid flame spray was used to deposit a TiO2 nanoparticle layer as the bottom
      layer for producing a suitable surface structure. The interstitial Al2O3
      nanofilm, fabricated by atomic layer deposition (ALD), stabilized the
      nanoparticle layer, and the topmost fluorosilane layer lowered the surface energy
      of the coating for enhanced omniphobicity. The coating was characterized with
      field emission scanning electron microscopy, focused ion beam scanning electron
      microscopy, x-ray photoelectron spectroscopy, contact angle (CA) and sliding
      angle (SA) measurements, and microscratch testing. The widely recognized
      requirements for superrepellency, i.e. CA > 150 degrees  and SA < 10 degrees ,
      were achieved for deioinized water, diiodomethane, and ethylene glycol. The
      mechanical stability of the coating could be varied by tuning the thickness of
      the ALD layer at the expense of repellency. To our knowledge, this is the
      thinnest superomniphobic coating reported so far, with the average thickness of
      about 70 nm.

PMID- 29451127
TI  - One-step hydrothermal synthesis of three-dimensional porous Ni-Co sulfide/reduced
      graphene oxide composite with optimal incorporation of carbon nanotubes for high
      performance supercapacitors.
AB  - Three-dimensional (3D) porous Ni-Co sulfide/reduced graphene oxide composite with
      the appropriate incorporation of carbon nanotubes (NCS/rGO/CNT) was fabricated as
      a promising material for supercapacitor electrodes. It combined the high pseudo
      capacitance of Ni-Co sulfide as well as the large specific surface area and
      electrical double layer capacitance of reduced graphene oxide (rGO). Carbon
      nanotubes (CNTs) were incorporated to act as the spacer for hindering the
      restacking of rGO and to construct a conductive network for enhancing the
      electron transport. The 3D porous NCS/rGO/CNT composite was fabricated by a
      facile one-step hydrothermal process in which Ni-Co sulfide nanosheets were
      synthesized and graphene oxide was reduced simultaneously. It was shown that the
      capacitance and cyclic performance indeed could be effectively improved via the
      appropriate addition of CNTs. In addition, a flexible all-solid-state asymmetric
      supercapacitor based on the NCS/rGO/CNT electrode was fabricated and exhibited
      the same capacitive electrochemical performance under bending. Also, it could
      successfully turn on a light-emitting diode light, revealing its feasibility in
      practical application. All results demonstrated that the developed NCS/rGO/CNT
      composite has potential application in supercapacitors.

PMID- 29451128
TI  - Signal-amplifying nanoparticle/hydrogel hybrid microarray biosensor for metal
      enhanced fluorescence detection of organophosphorus compounds.
AB  - In this study, we developed an enzyme-based miniaturized fluorescence biosensor
      to detect paraoxon, one of the most well-known neurotoxic organophosphorus
      compounds. The biosensor was fabricated with poly(ethylene glycol) (PEG) hydrogel
      microarrays that entrapped acetylcholinesterase (AChE) and quantum dots (QDs) as
      fluorescence reporters. Metal-enhanced fluorescence (MEF) was utilized to amplify
      the fluorescence signal, which was achieved by decorating QDs on the surface of
      silica-coated silver nanoparticles (Ag@Silica). The MEF effects of Ag@Silica were
      optimized by tuning the thickness of the silica shells, and under the optimized
      conditions, the fluorescence intensity was shown to be increased 5 fold, compared
      with the system without MEF. PEG hydrogel microarray entrapping QD-decorated
      Ag@Silica and AChE was prepared via photopatterning process. The entrapped AChE
      hydrolyzed paraoxon to produce p-nitrophenol within the hydrogel microstructure,
      which subsequently quenched the fluorescence of the QDs on the surface of
      Ag@Silica. The MEF-assisted fluorescence detection resulted in a significant
      enhancement of paraoxon detection. The detection limit was approximately 1.0 * 10
      10 M and 2.0 * 10-7 M for sensing with and without MEF, respectively. The
      successful integration of a hydrogel microarray system with a microfluidic system
      was demonstrated to be a potential application for the MEF-based micro-total
      analysis-system.

PMID- 29451129
TI  - Stress evolution of Ge nanocrystals in dielectric matrices.
AB  - Germanium nanocrystals (Ge NCs) embedded in single and multilayer silicon oxide
      and silicon nitride matrices have been synthesized using plasma enhanced chemical
      vapor deposition followed by conventional furnace annealing or rapid thermal
      processing in N2 ambient. Compositions of the films were determined by Rutherford
      backscattering spectrometry and x-ray photoelectron spectroscopy. The formation
      of NCs under suitable process conditions was observed with high resolution
      transmission electron microscope micrographs and Raman spectroscopy. Stress
      measurements were done using Raman shifts of the Ge optical phonon line at 300.7
      cm-1. The effect of the embedding matrix and annealing methods on Ge NC formation
      were investigated. In addition to Ge NCs in single layer samples, the stress on
      Ge NCs in multilayer samples was also analyzed. Multilayers of Ge NCs in a
      silicon nitride matrix separated by dielectric buffer layers to control the size
      and density of NCs were fabricated. Multilayers consisted of SiN y :Ge ultrathin
      films sandwiched between either SiO2 or Si3N4 by the proper choice of buffer
      material. We demonstrated that it is possible to tune the stress state of Ge NCs
      from compressive to tensile, a desirable property for optoelectronic
      applications. We also observed that there is a correlation between the stress and
      the crystallization threshold in which the compressive stress enhances the
      crystallization, while the tensile stress suppresses the process.

PMID- 29451130
TI  - Intrinsic optical signal imaging of the blood volume changes is sufficient for
      mapping the resting state functional connectivity in the rodent cortex.
AB  - OBJECTIVE: Resting state functional connectivity (RSFC) allows the study of
      functional organization in normal and diseased brain by measuring the spontaneous
      brain activity generated under resting conditions. Intrinsic optical signal
      imaging (IOSI) based on multiple illumination wavelengths has been used
      successfully to compute RSFC maps in animal studies. The IOSI setup complexity
      would be greatly reduced if only a single wavelength can be used to obtain
      comparable RSFC maps. APPROACH: We used anesthetized mice and performed various
      comparisons between the RSFC maps based on single wavelength as well as oxy-,
      deoxy- and total hemoglobin concentration changes. MAIN RESULTS: The RSFC maps
      based on IOSI at a single wavelength selected for sensitivity to the blood volume
      changes are quantitatively comparable to the RSFC maps based on oxy- and total
      hemoglobin concentration changes obtained by the more complex IOSI setups.
      Moreover, RSFC maps do not require CCD cameras with very high frame acquisition
      rates, since our results demonstrate that they can be computed from the data
      obtained at frame rates as low as 5 Hz. SIGNIFICANCE: Our results will have
      general utility for guiding future RSFC studies based on IOSI and making
      decisions about the IOSI system designs.

PMID- 29451131
TI  - Enhancement of radiation tolerance in GaAs/AlGaAs core-shell and InP nanowires.
AB  - Radiation effects on semiconductor nanowires (NWs) have attracted the attention
      of the research community due to their potential applications in space and atomic
      fields. The effective implementation of NW devices in a radiation environment is
      a matter of concern. Here, the photoluminescence (PL) and time-resolved PL (TRPL)
      measurements were performed on both GaAs and InP NWs at room temperature before
      and after 1 MeV H+ irradiation with fluences ranging from 1 * 1011 to 5 * 1013 p
      cm-2. It is found that the degradation of lifetime is size-dependent, and
      typically the minority carrier lifetime damage coefficient is closely correlated
      with the material and NW diameter. Compared to GaAs and InP bulk material
      counterparts, the lifetime damage coefficient of NWs decreases by a factor of
      about one order of magnitude. After irradiation, GaAs NWs with a smaller diameter
      show a much lower lifetime damage coefficient while InP NWs show an increase in
      carrier radiative lifetime. The increased size-dependent radiation hardness is
      mainly attributed to the defect sink effect and/or the improvement of a room
      temperature dynamic annealing mechanism of the NWs. The InP NWs also showed
      higher radiation tolerance than GaAs NWs.

PMID- 29451132
TI  - Synthesis of photothermal nanocomposites and their application to antibacterial
      assays.
AB  - In this work, we report a novel gold nanorod (AuNR)-based nanocomposite that
      shows strong binding to bacterium and high antibacterial efficiency. The AuNRs
      were used as a photothermal material to transform near-infrared radiation (NIR)
      into heat. We selected poly (acrylic acid) to modify the surface of the AuNRs
      based on a simple self-assembly method. After conjugation of the bacterium
      binding molecule vancomycin, the nanocomposites were capable of efficiently
      gathering on the cell walls of bacteria. The nanocomposites exhibited a high
      bacterial inhibition capability owing to NIR-induced heat generation in situ.
      Therefore, the prepared photothermal nanocomposites show great potential for use
      in antibacterial assays.

PMID- 29451133
TI  - Polyamide 6-LiCl nanofibrous membrane as low-temperature regenerative desiccant
      with improved stability.
AB  - Polyamide 6-LiCl (PA 6-LiCl) electrospun nanofibrous membranes (NFMs) have been
      successfully prepared as novel solid desiccant materials. The PA 6 NFM with 20%
      LiCl mass ratio had a sorption capacity of 1.8 g g-1 at 25  degrees C and 95%
      relative humidity, which was 4 times more than that of silica gels. The
      desorption isobars of the NFMs indicated that over 85% of sorbed water in the
      NFMs can be desorbed at about 50  degrees C, and the low regeneration temperature
      made it promising as an energy-saving desiccant material. The experimental
      results manifested that the sorption/desorption kinetics of the NFMs better fit
      the pseudo-second order model. According to scanning electron microscope images
      and the cycle experiment, the NFMs were also found to possess notably improved
      stability against moisture and could be recycled with little degradation of
      performance, which confirmed the practicability of the new desiccant membranes.

PMID- 29451134
TI  - A new route to gold nanoflowers.
AB  - Catanionic vesicles spontaneously formed by mixing the anionic surfactant bis(2
      ethylhexyl) sulfosuccinate sodium salt with the cationic surfactant
      cetyltrimethylammonium bromide were used as a reducing medium to produce gold
      clusters, which are embedded and well-ordered into the template phase. The gold
      clusters can be used as seeds in the growth process that follows by adding
      ascorbic acid as a mild reducing component. When the ascorbic acid was added very
      slowly in an ice bath round-edged gold nanoflowers were produced. When the same
      experiments were performed at room temperature in the presence of Ag+ ions, sharp
      edged nanoflowers could be synthesized. The mechanism of nanoparticle formation
      can be understood to be a non-diffusion-limited Ostwald ripening process of
      preordered gold nanoparticles embedded in catanionic vesicle fragments. Surface
      enhanced Raman scattering experiments show an excellent enhancement factor of 1.7
      . 105 for the nanoflowers deposited on a silicon wafer.

PMID- 29451135
TI  - Proximity coupling in superconductor-graphene heterostructures.
AB  - This review discusses the electronic properties and the prospective research
      directions of superconductor-graphene heterostructures. The basic electronic
      properties of graphene are introduced to highlight the unique possibility of
      combining two seemingly unrelated physics, superconductivity and relativity. We
      then focus on graphene-based Josephson junctions, one of the most versatile
      superconducting quantum devices. The various theoretical methods that have been
      developed to describe graphene Josephson junctions are examined, together with
      their advantages and limitations, followed by a discussion on the advances in
      device fabrication and the relevant length scales. The phase-sensitive properties
      and phase-particle dynamics of graphene Josephson junctions are examined to
      provide an understanding of the underlying mechanisms of Josephson coupling via
      graphene. Thereafter, microscopic transport of correlated quasiparticles produced
      by Andreev reflections at superconducting interfaces and their phase-coherent
      behaviors are discussed. Quantum phase transitions studied with graphene as an
      electrostatically tunable 2D platform are reviewed. The interplay between
      proximity-induced superconductivity and the quantum-Hall phase is discussed as a
      possible route to study topological superconductivity and non-Abelian physics.
      Finally, a brief summary on the prospective future research directions is given.

PMID- 29451136
TI  - Optimization of photoelectrochemical performance in Pt-modified p-Cu2O/n-Cu2O
      nanocomposite.
AB  - As it is expected to be one of the most promising materials for utilizing solar
      energy, Cu2O has attracted considerable attention with respect to the achievement
      of solar energy conversion. Until now, the photocurrent densities of all planar
      structure of the Cu2O photocathode have not even come close to the theoretical
      value of -14.7 mA cm-2 due to the incompatible light absorption and charge
      carrier diffusion lengths. Here, we have fabricated p-n Cu2O homojunction
      nanocomposite by multiple steps of electrochemical deposition processing with the
      optimization of deposition periods. The p-Cu2O/n-Cu2O nanocomposite fabricated by
      optimized pH (4.9) and deposition time (4 min) exhibited double the photocurrent
      density of that of the bare p-Cu2O photocathode. And the highest photocurrent
      density of nanostructured p-n Cu2O nanorod homojunction photocathode with a p
      Cu2O blocking layer reached -10.0 mA cm-2 at 0 V versus the reversible hydrogen
      electrode under simulated AM 1.5G illumination (100 mW cm-2).

PMID- 29451137
TI  - Self-assembled PCBM bilayers on graphene and HOPG examined by AFM and STM.
AB  - In this work we report fabrication and characterization of phenyl-C61-butyric
      acid methyl ester (PCBM) bilayer structures on graphene and highly oriented
      pyrolytic graphite (HOPG). Through careful control of the PCBM solution
      concentration (from 0.1 to 2 mg ml-1) and the deposition conditions, we
      demonstrate that PCBM molecules self-assemble into bilayer structures on graphene
      and HOPG substrates. Interestingly, the PCBM bilayers are formed with two
      distinct heights on HOPG, but only one unique representative height on graphene.
      At elevated annealing temperatures, edge diffusion allows neighboring vacancies
      to merge into a more ordered structure. This is, to the best of our knowledge,
      the first experimental realization of PCBM bilayer structures on graphene. This
      work could provide valuable insight into fabrication of new hybrid, ordered
      structures for applications to organic solar cells.

PMID- 29451139
TI  - Calcinosis cutis universalis in systemic sclerosis.

PMID- 29451138
TI  - Detection of Repair of the Zone of Calcified Cartilage with Osteoarthritis
      through Mesenchymal Stem Cells by Ultrashort Echo Time Magnetic Resonance
      Imaging.
AB  - Objective: Currently, magnetic resonance imaging (MRI) is the most commonly used
      imaging modality for observing the growth and development of mesenchymal stem
      cells (MSCs) after in vivo transplantation to treat osteoarthritis (OA). However,
      it is a challenge to accurately monitor the treatment effects of MSCs in the zone
      of calcified cartilage (ZCC) with OA. This is especially true in the
      physiological and biochemical views that are not accurately detected by MRI
      contrast agents. In contrast, ultrashort time echo (UTE) MRI has been shown to be
      sensitive to the presence of the ZCC, creating the potential for more effectively
      observing the repair of the ZCC in OA by MSCs. A special focus is given to the
      outlook of the use of UTE MRI to detect repair of the ZCC with OA through MSCs.
      The limitations of the current techniques for clinical applications and future
      directions are also discussed. Data Sources: Using the combined keywords:
      "osteoarthritis", "mesenchymal stem cells", "calcified cartilage", and "magnetic
      resonance imaging", the PubMed/MEDLINE literature search was conducted up to June
      1, 2017. Study Selection: A total of 132 published articles were initially
      identified citations. Of the 132 articles, 48 articles were selected after
      further detailed review. This study referred to all the important English
      literature in full. Results: In contrast, UTE MRI has been shown to be sensitive
      to the presence of the ZCC, creating the potential for more effectively observing
      the repair of the ZCC in OA by MSCs. Conclusions: The current studies showed that
      the ZCC could be described in terms of its histomorphology and biochemistry by
      UTE MRI. We prospected that UTE MRI has been shown the potential for more
      effectively observing the repair of the ZCC in OA by MSCs in vivo.

PMID- 29451140
TI  - Reticular telangiectatic erythema associated with implantable automatic
      cardioverter defibrillator.

PMID- 29451141
TI  - Associations between Body Composition Indices and Metabolic Disorders in Chinese
      Adults: A Cross-Sectional Observational Study.
AB  - Background: Obesity induces dyslipidemia, hypertension, glucose intolerance, and
      inflammatory state, which results in atherogenic processes, diabetes, and
      cardiovascular disease. We usually use body composition indices, such as body
      mass index (BMI), body fat percentage (BFP), waist circumference-height ratio
      (WHtR), and waist-hip ratio (WHR) to reflect the obesity. The aim of this large
      population-based cross-sectional study was to investigate the associations
      between body composition indices and metabolic parameters in Chinese adults.
      Methods: A total of 12,018 Chinese adults were included. Body composition
      indices, such as BMI, BFP, WHtR, and WHR, and metabolic parameters, such as
      systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol
      (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high
      density lipoprotein-cholesterol (HDL-C), fasting blood glucose (FBG), 2 h
      postprandial blood glucose (2h PBG), glycosylated hemoglobin (HbA1c), fasting
      insulin (FINS), insulin resistance index (HOMA-IR), high-sensitivity C-reactive
      protein (hs-CRP), and white blood cell count (WBC), were measured and analyzed.
      All analyses were stratified by gender. Results: All body composition indices and
      metabolic parameters except 2h PBG differed significantly between males and
      females (all P < 0.001). BMI was positively associated with SBP, DBP, LDL-C, TC,
      TG, FBG, 2h PBG, HbA1c, FINS, HOMA-IR, hs-CRP, and WBC, and inversely associated
      with HDL-C; similar relationships were identified between the metabolic
      parameters and BFP, WHtR, and WHR. In the multivariate analysis, the odds of
      impaired glucose regulation, dyslipidemia, insulin resistance, and increased hs
      CRP were 1.36, 1.92, 3.44, and 1.27 times greater in the overweight group than
      those in the normal weight group, respectively, and 1.66, 3.26, 7.53, and 1.70
      times greater in the obese group than those in the normal weight group,
      respectively. The odds of dyslipidemia and hs-CRP were 1.29 and 1.38 times
      greater in the BFP >=28.0% group than in the BFP <28.0% group, respectively. The
      odds of dyslipidemia, HOMA-IR, and hs-CRP were 1.55, 1.26, and 1.48 times greater
      in the WHtR >=0.96 group than in the WHtR <0.96 group, respectively. Among males,
      the odds of HOMA-IR were 1.46 times greater in the WHR >=0.54 group than in the
      WHR <0.54 group. Similar results were observed in females. Conclusions: This
      study identified positive associations between all evaluated body composition
      indices and metabolic parameters in Chinese adults. Among the body composition
      indices, BMI predicted four of the five evaluated metabolic disorders in both
      gender groups.

PMID- 29451142
TI  - Cost Analysis of Cervical Cancer Patients with Different Medical Payment Modes
      Based on Gamma Model within a Grade A Tertiary Hospital.
AB  - Background: Cervical cancer shows a growing incidence and medical cost in recent
      years that has increased severe financial pressure on patients and medical
      insurance institutions. This study aimed to investigate the medical economic
      characteristics of cervical cancer patients with different payment modes within a
      Grade A tertiary hospital to provide evidence and suggestions for inpatient cost
      control and to verify the application of Gamma model in medical cost analysis.
      Methods: The basic and cost information of cervical cancer cases within a Grade A
      tertiary hospital in the year 2011-2016 were collected. The Gamma model was
      adopted to analyze the differences in each cost item between medical insured
      patient and uninsured patients. Meanwhile, the marginal means of different cost
      items were calculated to estimate the influence of payment modes toward different
      medical cost items among cervical cancer patients in the study. Results:: A total
      of 1321 inpatients with cervical cancer between the 2011 and 2016 were collected
      through the medical records system. Of the 1321 cases, 65.9% accounted for
      medical insured patients and 34.1% were uninsured patients. The total inpatient
      medical expenditure of insured patients was RMB 29,509.1 Yuan and uninsured
      patients was RMB 22,114.3 Yuan, respectively. Payment modes, therapeutic options
      as well as the recurrence and metastasis of tumor toward the inpatient medical
      expenditures between the two groups were statistically significant. To the
      specifics, drug costs accounted for 37.7% and 33.8% of the total, surgery costs
      accounted for 21.5% and 25.5%, treatment costs accounted for 18.7% and 16.4%,
      whereas the costs of imaging and laboratory examinations accounted for 16.4% and
      15.2% for the insured patient and uninsured patients, respectively. As the
      effects of covariates were controlled, the total hospitalization costs, drug
      costs, treatment costs as well as imaging and laboratory examination costs showed
      statistical significance. The total hospitalization costs, drug costs, treatment
      costs as well as imaging and laboratory examination costs of insured patient were
      1.33, 1.42, 1.52, and 1.44 times of uninsured patients. Conclusions: The analysis
      of different payment modes toward the medical economic characteristics based on
      Gamma model is basically rational. Medical payment modes are having certain
      influence toward the hospitalization expenses of cervical cancer patients in an
      extent, as drug costs, treatment costs, and examination costs appear to be the
      main causes.

PMID- 29451143
TI  - Familial Nonmedullary Thyroid Carcinoma: A Retrospective Analysis of 117
      Families.
AB  - Background: The first and most important step in characterizing familial
      nonmedullary thyroid carcinoma (NMTC) is to distinguish the true familial
      patients, which is the prerequisite for all accurate analyses. This study aimed
      to investigate whether patients from families with >=3 first-degree relatives
      affected with NMTC have different characteristics than patients from families
      with only two affected members, and to compare these patients with those with
      sporadic disease. Methods:: We analyzed the clinicopathological features and
      prognosis of 209 familial and 1120 sporadic cases of NMTC. Familial patients were
      further divided into two subgroups: families with two affected members and
      families with >=3 affected members. Results:: The familial group had a
      significantly higher risk of bilateral growth, multifocality, extrathyroidal
      extension, and lateral lymph node metastasis than the sporadic group (P < 0.05).
      These main features were also different between the group with >=3 affected
      members and the sporadic group. The only difference between the two affected
      members' group and the sporadic group was incidence of multifocality (P < 0.05).
      The probability of disease recurrence in patients from families with >=3 affected
      members was significantly higher than that in sporadic cases (14.46% vs. 5.27%; P
      = 0.001), while the probability in patients from families with two affected
      members was similar to that in sporadic patients (6.35% vs. 5.27%; P = 0.610).
      The Kaplan-Meier survival analysis showed a statistically significant difference
      in disease-free survival between the two subgroups (85.54% vs. 93.65%; P =
      0.045). Conclusions:: Patients from families with >=3 members affected by NMTC
      have more aggressive features and a worse prognosis than those from families with
      only two affected members. Patients from families with >=3 affected first-degree
      relatives may be considered to have true familial NMTC.

PMID- 29451144
TI  - Moderate Dose of Trolox Preventing the Deleterious Effects of Wi-Fi Radiation on
      Spermatozoa In vitro through Reduction of Oxidative Stress Damage.
AB  - Background: The worsening of semen quality, due to the application of Wi-Fi, can
      be ameliorated by Vitamin E. This study aimed to demonstrate whether a moderate
      dose of trolox, a new Vitamin E, inhibits oxidative damage on sperms in vitro
      after exposure to Wi-Fi radiation. Methods: Each of the twenty qualified semen,
      gathered from June to October 2014 in eugenics clinic, was separated into four
      aliquots, including sham, Wi-Fi-exposed, Wi-Fi plus 5 mmol/L trolox, and Wi-Fi
      plus 10 mmol/L trolox groups. At 0 min, all baseline parameters of the 20 samples
      were measured in sequence. Reactive oxygen species, glutathione, and superoxide
      dismutase were evaluated in the four aliquots at 45 and 90 min, as were sperm DNA
      fragments, sperm mitochondrial potential, relative amplification of sperm
      mitochondrial DNA, sperm vitality, and progressive and immotility sperm. The
      parameters were analyzed by one-way analysis of variance and Tukey's posttest.
      Results: Among Wi-Fi plus 5 mmol/L trolox, Wi-Fi-exposed and Wi-Fi plus 10 mmol/L
      trolox groups, reactive oxygen species levels (45 min: 3.80 +/- 0.41 RLU.10-6.ml
      1 vs. 7.50 +/- 0.35 RLU.10-6.ml-1 vs. 6.70 +/- 0.47 RLU.10-6.ml-1, P < 0.001; 90
      min: 5.40 +/- 0.21 RLU.10-6.ml-1 vs. 10.10 +/- 0.31 RLU.10-6.ml-1 vs. 7.00 +/-
      0.42 RLU.10-6.ml-1, P < 0.001, respectively), percentages of tail DNA (45 min:
      16.8 +/- 2.0% vs. 31.9 +/- 2.5% vs. 61.3 +/- 1.6%, P < 0.001; 90 min: 19.7 +/-
      1.5% vs. 73.7 +/- 1.3% vs. 73.1 +/- 1.1%, P < 0.001, respectively), 8-hydroxy-2'
      deoxyguanosine (45 min: 51.89 +/- 1.46 pg/ml vs. 104.89 +/- 2.19 pg/ml vs. 106.11
      +/- 1.81 pg/ml , P = 0.012; 90 min: 79.96 +/- 1.73 pg/ml vs. 141.73 +/- 2.90
      pg/ml vs. 139.06 +/- 2.79 pg/ml; P < 0.001), and percentages of immotility sperm
      (45 min: 27.7 +/- 2.7% vs. 41.7 +/- 2.2% vs. 41.7 +/- 2.5%; 90 min: 29.9 +/- 3.3%
      vs. 58.9 +/- 4.0% vs. 63.1 +/- 4.0%; all P < 0.001) were lowest, and glutathione
      peroxidase (45 min: 60.50 +/- 1.54 U/ml vs. 37.09 +/- 1.77 U/ml vs. 28.18 +/-
      1.06 U/ml; 90 min: 44.61 +/- 1.23 U/ml vs. 16.86 +/- 0.93 U/ml vs. 29.94 +/- 1.56
      U/ml; all P < 0.001), percentages of head DNA (45 min: 83.2 +/- 2.0% vs. 68.2 +/-
      2.5% vs. 38.8 +/- 1.6%; 90 min: 80.3 +/- 1.5% vs. 26.3 +/- 1.3% vs. 26.9 +/-
      1.1%; all P < 0.001), percentages of sperm vitality (45 min: 89.5 +/- 1.6% vs.
      70.7 +/- 3.1% vs. 57.7 +/- 2.4%; 90 min: 80.8 +/- 2.2% vs. 40.4 +/- 4.0% vs. 34.7
      +/- 3.9%; all P < 0.001), and progressive sperm (45 min: 69.3 +/- 2.7% vs. 55.8
      +/- 2.2% vs. 55.4 +/- 2.5%; 90 min: 67.2 +/- 3.3% vs. 38.2 +/- 4.0% vs. 33.9 +/-
      4.0%; all P < 0.001) were highest in Wi-Fi plus 5 mmol/L trolox group at 45 and
      90 min, respectively. Other parameters were not affected, while the sham group
      maintained the baseline. Conclusion: This study found that 5 mmol/L trolox
      protected the Wi-Fi-exposed semen in vitro from the damage of electromagnetic
      radiation-induced oxidative stress.

PMID- 29451145
TI  - Patients Administered Neoadjuvant Chemotherapy Could be Enrolled into an Enhanced
      Recovery after Surgery Program for Locally Advanced Gastric Cancer.
AB  - Background: Most studies on enhanced recovery after surgery (ERAS) for gastric
      cancer exclude patients who received neoadjuvant chemotherapy. Here, we aimed to
      evaluate whether patients who received neoadjuvant chemotherapy can be enrolled
      into the ERAS program for locally advanced gastric cancer. Methods: From April
      2015 to July 2017, 114 patients who received neoadjuvant chemotherapy for locally
      advanced gastric cancer were randomized into ERAS and standard care (SC) groups.
      Postoperative length of stay, complications, bowel function, and nutritional
      status were recorded. Results:: The postoperative length of stay of the ERAS
      group was shorter compared with that of the SC group (5.9 +/- 5.6 vs. 8.1 +/- 5.3
      days, P = 0.037). The postoperative complication rate was 9.3% in the ERAS group
      and 11.5% in the SC group (P = 0.700). The time to first flatus (2.7 +/- 2.0 vs.
      4.5 +/- 4.6 days, P = 0.010) and time to a semi-liquid diet (3.2 +/- 2.1 vs. 6.3
      +/- 4.9 days, P < 0.001) in the ERAS group were shorter compared with those in
      the SC group. On the 10th day after surgery, the values of weight, total protein,
      albumin, and prealbumin of the ERAS group were lower compared with those of the
      SC group. Conclusions:: Patients who received neoadjuvant chemotherapy could be
      enrolled into ERAS programs for locally advanced gastric cancer. The nutritional
      status of these patients was not adversely affected.

PMID- 29451146
TI  - Safety and Efficiency of Trabectome-mediated Trabecular Meshwork Ablation for
      Chinese Glaucoma Patients: A Two-year, Retrospective, Multicentre Study.
AB  - Background: The aim of the study was to evaluate the long-term safety and
      efficacy of the Trabectome for Chinese glaucoma patients. Methods: This was a
      multicenter, retrospective, observational study. Glaucoma patients, except those
      with neovascular glaucoma, with/without a visually significant cataract were
      enrolled. The patients received Trabectome or a combined surgery with
      phacoemulsification and intraocular lens implantation. The primary outcome
      evaluation was a reduction in intraocular pressure (IOP), and the secondary
      outcomes were a reduction in glaucoma medication, the 2-year success percentages,
      and complications. Success was defined as an IOP <21 mmHg and at least a 20% IOP
      reduction from baseline after 3 months for any two consecutive visits, without
      additional glaucoma surgery. The data were processed using the R Stats Package
      version 3.0.0. The Wilcoxon test was used to compare the postoperative IOP and
      the number of glaucoma medications with baselines. The Kaplan-Meier test was used
      to calculate the 2-year success percentage. The risk factors related to
      Trabectome failure were determined by logistic regression. Results: A total of
      120 glaucoma patients were enrolled. The Trabectome efficiently reduced the IOP
      from a baseline of 22.8 +/- 1.34 mmHg to 17.6 +/- 0.96 mmHg, and the use of
      glaucoma medications from 2.2 +/- 0.17 mmHg to 1.4 +/- 0.21 in a 2-year follow-up
      (both, P < 0.01). The overall success percentage was 80%. No risk factor related
      to Trabectome failure was identified. No vision-threatening complication was
      observed. Ten patients, who required secondary glaucoma surgery, all reached the
      target IOP. Conclusions: In a 2-year follow-up, Trabectome was an efficient and
      safe procedure for Chinese glaucoma patients.

PMID- 29451147
TI  - Perioperative Single-Donor Platelet Apheresis and Red Blood Cell Transfusion
      Impact on 90-Day and Overall Survival in Living Donor Liver Transplantation.
AB  - Background:: Although many previous studies have confirmed that perioperative
      blood transfusion is associated with poor outcomes after liver transplantation
      (LT), few studies described the influence of single-donor platelet apheresis
      transfusion in living donor LT (LDLT). This study aimed to assess the effect of
      blood products on outcomes for LDLT recipients, focusing on apheresis platelets.
      Methods:: This retrospective study included 126 recipients who underwent their
      first adult-to-adult LDLT. Twenty-four variables including consumption of blood
      products of 126 LDLT recipients were assessed for their link to short-term
      outcomes and overall survival. Kaplan-Meier survival curve and the log-rank test
      were used for recipient survival analysis. A multivariate Cox proportional-hazard
      model and a propensity score analysis were applied to adjust confounders after
      potential risk factors were identified by a univariate Cox analysis. Results:
      Patients who received apheresis platelet transfusion had a lower 90-day
      cumulative survival (78.9% vs. 94.2%, P = 0.009), but had no significant
      difference in overall survival in the Cox model, compared with those without
      apheresis platelet transfusion. Units of apheresis platelet transfusion (hazard
      ratio [HR] = 3.103, 95% confidence interval [CI]: 1.720-5.600, P < 0.001) and
      preoperative platelet count (HR = 0.170, 95% CI: 0.040-0.730, P = 0.017) impacted
      90-day survival independently. Multivariate Cox regression analysis also found
      that units of red blood cell (RBC) transfusion (HR = 1.036, 95% CI: 1.006-1.067,
      P = 0.018), recipient's age (HR = 1.045, 95% CI: 1.005-1.086, P = 0.025), and ABO
      blood group comparison (HR = 2.990, 95% CI: 1.341-6.669, P = 0.007) were
      independent risk factors for overall survival after LDLT. Conclusions:: This
      study suggested that apheresis platelets were only associated with early
      mortality but had no impact on overall survival in LDLT. Units of RBC,
      recipient's age, and ABO group comparison were independent predictors of long
      term outcomes.

PMID- 29451148
TI  - Increased Endogenous Sulfur Dioxide Involved in the Pathogenesis of Postural
      Tachycardia Syndrome in Children: A Case-Control Study.
AB  - Background: The pathogenesis of postural tachycardia syndrome (POTS) remains
      unclear. This study aimed to explore the changes and significance of sulfur
      dioxide (SO2) in patients with POTS. Methods: The study included 31 children with
      POTS and 27 healthy children from Peking University First Hospital between
      December 2013 and October 2015. A detailed medical history, physical examination
      results, and demographic characteristics were collected. Hemodynamics was
      recorded and the plasma SO2was determined. Results: The plasma SO2was
      significantly higher in POTS children compared to healthy children (64.0 +/- 20.8
      MUmol/L vs. 27.2 +/- 9.6 MUmol/L, respectively, P < 0.05). The symptom scores in
      POTS were positively correlated with plasma SO2levels (r = 0.398, P < 0.05). In
      all the study participants, the maximum heart rate (HR) was positively correlated
      with plasma levels of SO2(r = 0.679, P < 0.01). The change in systolic blood
      pressure from the supine to upright (DeltaSBP) in POTS group was smaller than
      that in the control group (P < 0.05). The DeltaSBP was negatively correlated with
      baseline plasma SO2levels in all participants (r = -0.28, P < 0.05). In the
      control group, DeltaSBP was positively correlated with the plasma levels of SO2(r
      = 0.487, P < 0.01). The change in HR from the supine to upright in POTS was
      obvious compared to that of the control group. The area under curve was 0.967
      (95% confidence interval: 0.928-1.000), and the cutoff value of plasma SO2 level
      >38.17 MUmol/L yielded a sensitivity of 90.3% and a specificity of 92.6% for
      predicting the diagnosis of POTS. Conclusions: Increased endogenous SO2levels
      might be involved in the pathogenesis of POTS.

PMID- 29451150
TI  - Identification of Seven Novel Mutations in the Acid Alpha-glucosidase Gene in
      Five Chinese Patients with Late-onset Pompe Disease.
AB  - Background: Pompe disease is a rare lysosomal glycogen storage disorder linked to
      the acid alpha-glucosidase gene (GAA). A wide clinical and genetic variability
      exists between patients from different ethnic populations, and the genotype
      phenotype correlations are still not well understood. The aim of this study was
      to report the clinicopathological and genetic characteristics of five Chinese
      patients with late-onset Pompe disease (LOPD) who carried novel GAA gene
      mutations. Methods: Clinical and pathological data of patients diagnosed with
      glycogen storage disease at our institution from April 1986 to August 2017 were
      collected, and next-generation sequencing of frozen muscle specimens was
      conducted. Results: Of the five patients included in the study, the median
      disease onset age was 13 years, with a median 5 years delay in diagnosis. The
      patients mainly manifested as progressive weakness in the proximal and axial
      muscles, while one patient developed respiratory insufficiency that required
      artificial ventilation. In muscle biopsies, vacuoles with variable sizes and
      shapes appeared inside muscle fibers, and they stained positive for both periodic
      acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including
      seven novel ones (c.796C>A, c.1057C>T, c.1201C>A, c.1780C>T, c.1799G>C,
      c.2051C>A, c.2235dupG), were identified by genetic tests. Conclusions: The seven
      novel GAA gene mutations revealed in this study broaden the genetic spectrum of
      LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.

PMID- 29451149
TI  - A Study on Clinical Characteristics and Magnetic Resonance Imaging Manifestations
      on Systemic Rosai-Dorfman Disease.
AB  - Background:: Rosai-Dorfman disease (RDD) is typically characterized by painless
      bilateral and symmetrical cervical lymphadenopathy, with associated fever and
      leukocytosis. The aim of the current study was to summarize the clinical features
      and imaging characteristics of RDD, in an effort to improve its diagnostic
      accuracy. Methods: The study was analyzed from 32 patients between January 2011
      and December 2017; of these, 16 patients had pathologically diagnosed RDD, eight
      had pathologically diagnosed meningioma, and eight pathologically diagnosed
      lymphoma. All patients underwent computed tomography and magnetic resonance
      imaging (MRI). Clinical features and imaging characteristics of RDD were analyzed
      retrospectively. The mean apparent diffusion coefficient (ADC) values of lesions
      at different sites were measured, and one-way analysis of variance and the least
      significant difference t-test were used to compare the differences between groups
      and draw receiver operating characteristic curves. The tumors were excised for
      biopsy and analyzed using immunohistochemistry. Results:: The mean ADCs were
      (0.81 +/- 0.10) * 10-3 mm2/s for intercranial RDD, (0.73 +/- 0.05) * 10-3 mm2/s
      for nasopharyngeal RDD, (0.74 +/- 0.11) * 10-3 mm2/s for bone RDD, and (0.71 +/-
      0.04) * 10-3 mm2/s for soft-tissue RDD. The optimum ADC to distinguish
      intracranial RDD from lymphoma was 0.79 * 10-3 mm2/s (62.5% sensitivity and 100%
      specificity) and to distinguish meningioma from intracranial RDD was 0.92 * 10-3
      mm2/s (62.5% sensitivity and 100% specificity). Levels of C-reactive protein,
      erythrocyte sediment rate and D-dimer were significantly elevated (81%, 87%, and
      75%, respectively). On immunohistochemistry, RDD was positive for both S-100 and
      CD68 proteins but negative for CD1a. Conclusions:: Conventional MRI, combined
      with diffusion-weighted imaging and ADC mapping, is an important diagnostic tool
      in evaluating RDD patients. An accurate diagnosis of RDD should consider the
      clinical features, imaging characteristics, and the pathological findings.

PMID- 29451151
TI  - Exosomal MicroRNA-10a Is Associated with Liver Regeneration in Rats through
      Downregulation of EphA4.
AB  - Background: MicroRNAs (miRNAs) have been reported to play vital roles in liver
      regeneration. Previous studies mainly focused on the functions of intracellular
      miRNAs, while the functions of circulating exosomal miRNAs in liver regeneration
      remain largely unknown. The aim of this study was to identify the key exosomal
      miRNA that played vital roles in liver regeneration. Methods: The Sprague-Dawley
      male rats were assigned to 70% partially hepatectomized group (n = 6) and sham
      surgery group (n = 6). The peripheral blood of both groups was collected 24 h
      after surgery. The exosomal miRNAs were extracted, and microarray was used to
      find out the key miRNA implicated in liver regeneration. Adenovirus was used to
      overexpress the key miRNA in rats, and proliferating cell nuclear antigen (PCNA)
      staining was applied to study the effect of key miRNA overexpression on liver
      regeneration. Western blotting was used to validate the predicted target of the
      key miRNA. Results: Exosomal miR-10a was upregulated more than nine times in
      hepatectomized rats. The level of miR-10a was increased in the early phase of
      liver regeneration, reached the top at 72 h postsurgery, and decreased to
      perioperative level 168 h after surgery. Moreover, enforced expression of miR-10a
      by adenovirus facilitated the process of liver regeneration as evidenced by
      immunohistochemical staining of PCNA. Erythropoietin-producing hepatocellular
      receptor A4 (EphA4) has been predicted to be a target of miR-10a. The protein
      level of EphA4 was decreased in the early phase of liver regeneration, reached
      the bottom at 72 h postsurgery, and rose to perioperative level 168 h after
      surgery, which was negatively correlated with miR-10a, confirming that EphA4
      served as a downstream target of miR-10a. Moreover, inhibition of EphA4 by
      rhynchophylline could promote the proliferation of hepatocytes by regulating the
      cell cycle. Conclusion: Exosomal miR-10a might accelerate liver regeneration
      through downregulation of EphA4.

PMID- 29451152
TI  - Different Effects of Pravastatin on Preeclampsia-like Symptoms in Different Mouse
      Models.
AB  - Background: Pravastatin (Pra) exerts protective effects on preeclampsia.
      Preeclampsia is a multifactorial and pathogenic pathway syndrome. The present
      study compared the effects of Pra on clinical manifestations of preeclampsia in
      different pathogenic pathways. Methods: Two different preeclampsia-like mouse
      models used in this study were generated with Nomega-nitro-L-arginine methyl
      ester (L-NAME) and used lipopolysaccharide (LPS) from day 7 of gestation,
      respectively. Pra treatment was administered on day 2 after the models were
      established in each group (L-NAME + Pra, LPS + Pra, and Control + Pra, n = 8) or
      normal saline (NS) for the control group (L-NAME + NS, LPS + NS, and Control +
      NS, n = 8). Maternal weight, serum lipids, the histopathological changes, and
      lipid deposition in the liver and placenta were observed. The pregnancy outcomes
      were compared. The blood pressure analysis was carried out on repeated
      measurements of variance. Student's t-test was used for comparing the two groups.
      The enumeration data were compared by Chi-square test. Results: The mean arterial
      pressure (MAP) and 24-h urinary protein in the L-NAME + NS and LPS + NS groups
      were significantly higher than the Control + NS group (F = 211.05 and 309.92 for
      MAP, t = 6.63 and 8.63 for 24-h urinary protein; all P < 0.05) and reduced in the
      L-NAME + Pra group as compared to the L-NAME + NS group (F = 208.60 for MAP, t =
      6.77 for urinary protein; both P < 0.05). Urinary protein was decreased in the
      LPS + Pra group as compared to the LPS + NS group (t = 5.33; P < 0.05), whereas
      MAP had no statistical significance (F = 3.37; P > 0.05). Compared to the Control
      + NS group, the placental efficiency in the L-NAME + NS and LPS + NS groups
      decreased significantly (t = 3.09 and 2.89, respectively; both P < 0.05);
      however, no significant difference was observed in L-NAME + Pra and LPS + Pra
      groups (t = 1.37 and 0.58, respectively; both P > 0.05). Free fatty acid was
      elevated in the L-NAME + NS group as compared to the Control + NS group (t =
      3.99; P < 0.05) at day 18 of pregnancy and decreased in the L-NAME + Pra group as
      compared to the L-NAME + NS group (t = 3.28; P < 0.05); however, no significant
      change was observed in the LPS model (F = 0.32; P > 0.05). Conclusion: This study
      suggested that Pra affected the clinical manifestations differently in
      preeclampsia-like mouse models generated in various pathogenic pathways.

PMID- 29451154
TI  - Novel Mutations in SCN4A Gene Cause Myotonia Congenita with Scoliosis.

PMID- 29451153
TI  - Effects of Plasma Lipids and Statins on Cognitive Function.
AB  - Objective:: Dementia is the fourth most common cause of death in developed
      countries. The relationship between plasma lipids and cognitive function is
      complex and controversial. Due to the increasing life expectancy of the
      population, there is an urgent need to control vascular risk factors and to
      identify therapies to prevent and treat both cognitive impairment and dementia.
      Here, we reviewed the effects of plasma lipids and statins on cognitive function.
      Data Sources:: We searched the PubMed database for research articles published
      through November 2017 with key words including "plasma lipids," "hyperlipidemia,"
      "hypercholesterolemia," "statins," and "cognition function." Study Selection::
      Articles were retrieved and reviewed to analyze the effects of plasma lipids and
      statins on cognitive function and the mechanisms underlying these effects.
      Results:: Many studies have examined the relationship between plasma lipids and
      cognitive function, but no definitive conclusions can be drawn. The mechanisms
      involved may include blood-brain barrier injury, the influence on small blood
      vessels in the brain, the influence on amyloid deposition, and a neuroprotective
      effect. To date, most studies of statins and cognition have been observational,
      with few randomized controlled trials. Therefore, firm conclusions regarding
      whether mid- or long-term statin use affects cognition function and dementia
      remain elusive. However, increasing concern exists that statins may be a
      causative factor for cognitive problems. These adverse effects appear to be rare
      and likely represent a yet-to-be-defined vulnerability in susceptible
      individuals. Conclusions:: The association between plasma lipids and cognition,
      the mechanism of the influence of plasma lipids on cognitive function, and the
      association between statins and cognitive function are complex issues and
      currently not fully understood. Future research aimed at identifying the
      mechanisms that underlie the effects of plasma lipids and statins on cognition
      will not only provide important insight into the causes and interdependencies of
      cognitive impairment and dementia, but also inspire novel strategies for treating
      and preventing these cognitive disorders.

PMID- 29451155
TI  - Proteomic Analysis of the Serum of Patients with Stable Vitiligo and Progressive
      Vitiligo.

PMID- 29451156
TI  - Intravascular Foreign Bodies: A Single-Institution Experience and Description of
      a Novel Modified Percutaneous Retrieval Technique.

PMID- 29451158
TI  - Lymphangioma Circumscriptum in Vulva with Klippel-Trenaunay Syndrome.

PMID- 29451157
TI  - Current Research of Chlamydial Infection Diseases in China.

PMID- 29451159
TI  - Use of Rectal Swab Samples for Analysis of the Intestinal Microbiome in Children.

PMID- 29451160
TI  - Wogonin Inhibits Growth of Mantle Cell Lymphoma Cells through Nuclear Factor
      kappaB Signaling Pathway.

PMID- 29451161
TI  - Clinical Characteristics of Pneumonia in Chinese Hemodialysis Patients.

PMID- 29451162
TI  - Four Case Reports of Endometriosis-Related Hemoperitoneum in Pregnancy.

PMID- 29451163
TI  - EUS-guided gallbladder drainage: Current status and future prospects.

PMID- 29451164
TI  - EUS-guided biliary drainage: A comprehensive review of the literature.
AB  - EUS-guided biliary drainage (EUS-BD) has emerged as a technique for gaining
      biliary access when ERCP fails. This article gives a comprehensive review on the
      role and technique of EUS-BD. Moreover, we propose an algorithm guiding the
      clinician when to consider EUS-BD after failed ERCP or in anticipated difficult
      cannulations.

PMID- 29451166
TI  - Molecular analysis of pancreatic cyst fluid changes clinical management.
AB  - Background and Objectives: DNA molecular analysis has been suggested as a tool to
      evaluate pancreatic cysts. This study assesses whether the addition of DNA
      molecular analysis alters clinical management. Methods: This is a retrospective
      review of 46 consecutive patients who underwent EUS-FNA of pancreatic cysts with
      DNA molecular analysis at two major academic institutions. Cases were presented
      to two pancreaticobiliary surgeons first without and then with DNA molecular
      analysis data. The primary outcome was the frequency with which clinical
      management was altered with the addition of DNA molecular analysis. Results:
      Forty-six patients with a mean age of 62.0 (+/-13.4) years and mean cyst size of
      3.2 (+/-2.3) cm were included in the study. Cyst carcinoembryonic antigen (CEA)
      was available in 30 patients and ranged from 0.4 to 15,927 ng/mL. DNA molecular
      analysis was described as benign in 23 (50%), statistically indolent in 13 (28%),
      statistically higher risk in 9 (20%), and indeterminate in 1 (2%). Surgeon #1
      changed the management in 13/46 cases (28%) and surgeon #2 changed the management
      in 12/46 cases (26%) with the addition of DNA molecular analysis. When organized
      by CEA concentration, those with an intermediate CEA (45-800 ng/mL) or without a
      CEA concentration had a management changed more frequently (40%) compared to all
      others (P < 0.05). Conclusions: The addition of DNA molecular analysis alters the
      clinical management of pancreatic cystic lesions most often when CEA levels are
      intermediate (45-800 ng/mL) or when no CEA concentration is available. Use of DNA
      molecular analysis can be considered in this cohort. Further study of molecular
      markers in pancreatic cystic lesions is recommended.

PMID- 29451165
TI  - EUS elastography: How to do it?
AB  - Strain elastography as used in EUS (EUS-real-time tissue elastography [RTE]) is a
      qualitative technique and provides information on the relative stiffness between
      one tissue and another. This article reviews the principles, technique, and
      interpretation of EUS-RTE in various organs. It includes information on how to
      optimize the technique as well as a discussion on pitfalls and artifacts. We also
      refer to the article describing RTE using conventional ultrasound transducers.

PMID- 29451167
TI  - A Multicenter comparative trial of a novel EUS-guided core biopsy needle
      (SharkCoreTM) with the 22-gauge needle in patients with solid pancreatic mass
      lesions.
AB  - Background and Objectives: The ability to obtain adequate tissue of solid
      pancreatic lesions by EUS-guided remains a challenge. The aim of this study was
      to compare the performance characteristics and safety of EUS-FNA for evaluating
      solid pancreatic lesions using the standard 22-gauge needle versus a novel EUS
      biopsy needle. Methods: This was a multicenter retrospective study of EUS-guided
      sampling of solid pancreatic lesions between 2009 and 2015. Patients underwent
      EUS-guided sampling with a 22-gauge SharkCore (SC) needle or a standard 22-gauge
      FNA needle. Technical success, performance characteristics of EUS-FNA, the number
      of needle passes required to obtain a diagnosis, diagnostic accuracy, and
      complications were compared. Results: A total of 1088 patients (mean age = 66
      years; 49% female) with pancreatic masses underwent EUS-guided sampling with a 22
      gauge SC needle (n = 115) or a standard 22-gauge FNA needle (n = 973). Technical
      success was 100%. The frequency of obtaining an adequate cytology by EUS-FNA was
      similar when using the SC and the standard needle (94.1% vs. 92.7%,
      respectively). The sensitivity, specificity, and diagnostic accuracy of EUS-FNA
      for tissue diagnosis were not significantly different between two needles.
      Adequate sample collection leading to a definite diagnosis was achieved by the
      1st, 2nd, and 3rd pass in 73%, 92%, and 98% of procedures using the SC needle and
      20%, 37%, and 94% procedures using the standard needle (P < 0.001), respectively.
      The median number of passes to obtain a tissue diagnosis using the SC needle was
      significantly less as compared to the standard needle (1 and 3, respectively; P<
      0.001). Conclusions: The EUS SC biopsy needle is safe and technically feasible
      for EUS-FNA of solid pancreatic mass lesions. Preliminary results suggest that
      the SC needle has a diagnostic yield similar to the standard EUS needle and
      significantly reduces the number of needle passes required to obtain a tissue
      diagnosis.

PMID- 29451168
TI  - Percutaneous catheter drainage followed by endoscopic transluminal
      drainage/necrosectomy for treatment of infected pancreatic necrosis in early
      phase of illness.
AB  - Background and Objectives: Infected pancreatic necrosis (IPN) in the early phase
      is treated with "step up approach" involving initial percutaneous catheter
      drainage (PCD) followed by necrosectomy. There is a paucity of data on a combined
      approach of initial PCD followed by endoscopic drainage and necrosectomy. A
      retrospectively study on safety and efficacy of initial PCD followed by
      endoscopic transluminal drainage and necrosectomy in IPN. Methods: Retrospective
      analysis of data of 23 patients with IPN who were treated with a combined
      approach. Patients were divided into two groups as follows: patients with central
      necrosis in whom PCD and endoscopic drainage were done in the same collection (n
      = 11) and patients with combined central and peripheral necrosis where PCD was
      placed in peripheral necrosis, and endoscopic drainage was done for central
      necrosis (n = 12). Results: Endoscopic drainage could be done successfully in all
      23 patients with mean time for the resolution being 4.0 +/- 0.9 weeks. Fifteen
      (65.2%) patients were successfully treated using multiple plastic stents while
      direct endoscopic necrosectomy (DEN) was needed in 8 (34.8%) patients and fully
      covered self-expanding metal stent was inserted in 6 (26%) patients. The number
      of endoscopic sessions needed were 3 in 3 (13%), 4 in 9 (39%) patients, 5 in 5
      (22%), 6 in 3 (13%), and 7 in 3 (13%) patients, respectively. Patients of central
      walled-off pancreatic necrosis (WOPN) with PCD catheter in situ needed more
      endoscopic sessions for resolution as well as more frequently needed DEN in
      comparison to patients with central WOPN with no PCD catheter. Conclusion: The
      combined approach of initial PCD followed by endoscopic drainage and necrosectomy
      is safe and effective treatment alternative for patients with IPN.

PMID- 29451169
TI  - Patient perception and preference of EUS-guided drainage over percutaneous
      drainage when endoscopic transpapillary biliary drainage fails: An international
      multicenter survey.
AB  - Background and Objectives: EUS-guided biliary drainage (EUS-BD) is a feasible
      procedure when ERCP fails, as is percutaneous transhepatic BD (PTBD). However,
      little is known about patient perception and preference of EUS-BD and PTBD.
      Patients and Methods: An international multicenter survey was conducted in seven
      tertiary referral centers. In total, 327 patients, scheduled to undergo ERCP for
      suspected malignant biliary obstruction, were enrolled in the study. Patients
      received decision aids with visual representation regarding the techniques,
      benefits, and adverse events (AEs) of EUS-BD and PTBD. Patients were then asked
      the choice between the two simulated scenarios (EUS-BD or PTBD) after failed
      ERCP, the reasons for their preference, and whether altering AE rates would
      influence their prior choice. Results: In total, 313 patients (95.7%) responded
      to the questionnaire and 251 patients (80.2%) preferred EUS-BD. The preference of
      EUS-BD was 85.7% (186/217) with EUS-BD expertise, compared to 67.7% (65/96)
      without EUS-BD expertise (P < 0.001). The main reason for choosing EUS-BD was the
      possibility of internal drainage (78.1%). In multivariate analysis, the
      availability of EUS-BD expertise was the single independent factor that
      influenced patient preference (odds ratio: 3.168; 95% of confidence interval,
      1.714-5.856; P < 0.001). The preference of EUS-BD increased as AE rates decreased
      (P < 0.001). Conclusions: In this simulated scenario, approximately 80% of
      patients preferred EUS-BD over PTBD after failed ERCP. However, preference of EUS
      BD declined as its AE rates increased. Further technical innovations and improved
      proficiency in EUS-BD for reducing AEs may encourage the use of this procedure as
      a routine clinical practice when ERCP fails.

PMID- 29451171
TI  - An unusual complication of cardia occlusion with lumen-apposing metal stent
      therapy for pancreatic pseudocyst.

PMID- 29451170
TI  - EUS-FNA using 22G nitinol or ProCore needles without on-site cytopathology.
AB  - Objectives: The project is aimed to compare the tissue sampling rate and the
      diagnostic accuracy rate of EUS-FNA using 22G nitinol and reverse bevel-tipped
      needles. Subjects and Methods: This was a prospective, randomized, crossover
      study in a tertiary academic hospital. All consecutive adult patients undergoing
      EUS-guided FNA for lesions > 2 cm were recruited. Patients fulfilling the
      inclusion and exclusion criteria underwent EUS-guided FNA using both needles in
      sequence. They were randomized on a 1:1 basis to determine whether EUS-FNA would
      be performed first using the 22G reverse bevel-tipped (ProCore) needle followed
      by the nitinol needle or vice versa. The patients and the pathologists were
      blinded to the type of needle used. Results: Forty patients with suspected
      malignant neoplasms were recruited to the study. No significant differences were
      found in the diagnostic yield (76.9% vs. 84.6%, P = 0.389), accuracy (71.8% vs.
      84.6%, P = 0.170), sensitivity (77.8% vs. 86.1%, P = 0.358), specificity (100%
      vs. 100%, P = 1), positive predictive value (100% vs. 100%, P = 1), and negative
      predictive value (20.0% vs. 28.6%, P = 1). The percentage of obtained tissue for
      histological assessment was also similar (41.0% vs. 46.2%, P = 0.648). In terms
      of the quantity of tissue obtained with the needles, a larger proportion of
      patients in the nitinol group obtained more tissue for assessment (P = 0.003).
      Conclusion: The tissue-sampling rate and the diagnostic accuracy of the new 22G
      ProCore needle were comparable to the conventional 22G FNA needle in the absence
      of an on-site cytopathologist.

PMID- 29451172
TI  - A case of gastric wall implantation caused by EUS-FNA 22 months after pancreatic
      cancer resection.

PMID- 29451173
TI  - Stent release within scope channel technique to prevent stent migration during
      EUS-guided hepaticogastrostomy (with video).

PMID- 29451174
TI  - Stent Tracker app: Novel method to track patients with indwelling lumen-apposing
      metal stents.

PMID- 29451175
TI  - EUS-guided fine-needle biopsy for histological examination: Is it time to change
      our sampling technique?

PMID- 29451176
TI  - Peroral endoscopic myotomy using tailored accessories.

PMID- 29451177
TI  - The association between nonselective beta-blockers and portal venous thrombosis
      in cirrhotic patients: More questions on the horizon.

PMID- 29451178
TI  - Involvement of epithelial-mesenchymal transition in liver fibrosis.
AB  - Fibrosis of the liver is an inherent wound healing response to chronic liver
      injury. Regeneration of liver epithelium and restoration of normal liver
      structure were generally involved in this process. Although the liver has a
      striking capacity to adapt to damage through tissue repair, excessive
      accumulation of extracellular matrix during this process often leads to scar
      tissue formation and subsequent fibrosis. Epithelial to mesenchymal transition
      (EMT) enables a polarized epithelial cell to undergo multiple changes
      biochemically and to bear a mesenchymal cell phenotype. EMT plays a critical role
      in tissue and organ development and embryogenesis. In the liver, it is proposed
      that epithelial cells can acquire fibroblastic phonotype via EMT and contribute
      to fibrogenesis. This made EMT a potential target for antifibrotic strategies.
      Following an original passion, many investigators devote themselves to exploring
      this mechanism in liver fibrosis. However, as research continues, this hypothesis
      became highly controversial. The exact contribution of EMT to fibrogenesis was
      challenged due to the contradictory results from related studies. In this review,
      we summarized the recent advances regarding EMT in hepatic fibrosis and discussed
      the potentially involved liver cell types and pathways in order to reach rational
      and helpful conclusions.

PMID- 29451179
TI  - Sarcopenia and risk of nonalcoholic fatty liver disease: A meta-analysis.
AB  - Background/Aim: The association between sarcopenia and nonalcoholic fatty liver
      disease (NAFLD) has been suggested by recent epidemiological studies, although
      the results have been inconsistent. This meta-analysis was conducted to summarize
      all available data and estimate the risk of NAFLD among patients with sarcopenia.
      Materials and Methods: A comprehensive literature review was conducted using
      MEDLINE and EMBASE databases through November 2016 to identify all studies that
      compared the risk of NAFLD among patients with sarcopenia versus those without
      sarcopenia. Effect estimates from each study were extracted and combined using
      the random-effect, generic inverse variance method of DerSimonian and Laird.
      Results: Five cross-sectional studies with 27,804 participants met the
      eligibility criteria and were included in the meta-analysis. The risk of NAFLD in
      patients with sarcopenia was significantly higher than those without sarcopenia
      with the pooled odds ratio of 1.54 (95% confidence interval, 1.05-2.26). The
      statistical heterogeneity was high with an I2of 83%. Conclusions: A significantly
      increased risk of NAFLD among patients with sarcopenia was observed in this
      study.

PMID- 29451180
TI  - Outcome of peroral endoscopic myotomy in achalasia cardia: Experience with a new
      triangular knife.
AB  - Background and Aim: Peroral endoscopic myotomy (POEM) is a technically demanding
      procedure. Recently, a new triangular knife with integrated water jet function
      (TTJ) has been introduced. The present study was aimed to analyze and compare the
      operating time, efficacy, and adverse events (AEs) between the conventional (TT
      knife) and new knife (TTJ). Patients and Methods: All patients with achalasia
      cardia (AC) who underwent POEM between August 2015 and November 2016 were
      analyzed retrospectively. Operating time (OT), technical success, and AEs were
      assessed and compared between TT and TTJ knife. Results: A total of 193 patients
      with AC underwent POEM during the specified period. Both groups had equivalent
      number of different subtypes of AC (I, II, and III). There was no difference in
      technical success between the two groups (TT, 99% vs TT, 98.9%). OT was
      significantly less in the TTJ group as compared to TT group (53.8 +/- 15.2 vs
      66.26 +/- 19.2; P = 0.0001). On subanalysis, OT taken for submucosal tunneling
      was significantly less with TTJ knife (34.6 +/- 10.1 vs 45.83 +/- 14.80), whereas
      OT was similar for myotomy and clipping in both the groups. Significantly fewer
      use of coagulation forceps and exchanges of accessories were required in TTJ
      knife group (2.92 +/- 1.77 vs 10.5 +/- 3.58; P = 0.0001). There were no major
      AEs. Minor AEs were noted in 21.5% and 31% of patients in TTJ and TT knife
      groups, respectively. Conclusion: New triangular knife reduces procedure time and
      technical difficulty with POEM. POEM is an efficacious treatment for achalasia
      and can be safely executed in an endoscopy unit.

PMID- 29451181
TI  - The use of nonselective beta blockers is a risk factor for portal vein thrombosis
      in cirrhotic patients.
AB  - Background/Aim: A reduction in portal vein inflow velocity seems to predispose to
      the emergence of portal vein thrombosis (PVT). Nonselective beta-blockers
      (NSBBs), used to prevent variceal bleeding, may increase the development of PVT
      by reducing portal vein inflow velocity. In this retrospective case-control
      study, we evaluated the risk factors and clinical features of a first event of
      PVT in 130 cirrhotics, 19 (15%) with (PVT group) and 111 (85%) without PVT (non
      PVT group). Patients and Methods: Patient evaluation and NNBB treatment were
      carried out according to the AASLD guidelines. Results: PVT was prevalently
      partial (84%) and asymptomatic (84%). Patients with PVT were treated with
      different regimens, and resolution of thrombosis was observed in about 50% of the
      cases. In both groups, HCV was the most frequent cause of cirrhosis and Child
      Pugh score A was prevalent. Ascites and esophageal varices were more frequent in
      the PVT group (P = 0.05 and <0.000, respectively). Treatment with NSBBs was
      significantly more frequent in the PVT group than in the non-PVT group (P <
      0.000). PVT was associated with higher prevalence of chronic renal disease (P =
      0.002), higher PT impairment (P = 0.003) and lower AST and ALT (P = 0.000). At
      multivariate logistic regression analysis, history of esophageal varices (P =
      0.007) and NSBB treatment (P = 0.0003) were independent risk factors
      significantly associated with PVT. Conclusions: Esophageal varices and NSBB
      treatment were independent risk factors of PVT. Larger studies should evaluate
      the risk between variceal bleeding and portal vein thrombosis of using NSBBs,
      particularly in the prevention of first bleeding in nonadvanced liver cirrhosis.

PMID- 29451182
TI  - Host genetic factors in predicting response status in chronic hepatitis B
      patients discontinuing nucleos(t)ide analogs.
AB  - Background/Aims: The optimal duration of nucleos(t)ide analogs (NAs) therapy in
      chronic hepatitis B (CHB) patients remains unsatisfactory. Previous studies have
      confirmed the important role of host genetic factors in determining the outcome
      of HBV infection. This study tries to determine the role of host genetic factors
      in predicting response status in CHB patients discontinuing NAs according to
      stringent cessation criteria. Patients and Methods: Participating patients came
      from a prospective NAs- discontinuation cohort since June 1999. Six single
      nucleotide polymorphisms (SNPs) were selected according to previous report.
      SNaPshot assay was used for DNA SNPs analyses. Results: Seventy-six CHB patients
      were enrolled in our study, of which 61 patients were HBeAg-positive and 15
      patients were HBeAg-negative. rs1883832 in the Kozak sequence of CD40 displayed
      an AUROC of 0.778 in predicting response status in CHB patients with HBeAg
      seroconversion and a genotype of CT was associated with sustained response in
      this subpopulation. The diagnostic performance of combinative index (rs1883832,
      age, and HBsAg at discontinuation) seemed to be better than that of rs1883832,
      but no statistical difference was observed. rs1883832 was also evaluated as an
      independent factor for response status by multivariate logistic regression. For
      HBeAg-negative CHB patients, rs9277535 at HLA-DP presents a Spearman correlation
      coefficient of 0.582 (P = 0.023) with virological relapse after discontinuation
      of NAs. Conclusions: rs1883832 serves as a valuable predictive factor for CHB
      patients with HBeAg seroconversion. rs9277535 at HLA-DP might also be a valuable
      predictive factor for CHB patients with HBeAg-negative, however, further
      verifications are recommended due to study limitations.

PMID- 29451183
TI  - The Level of TWIST1 expression determines the response of colon cancer cells to
      mitogen-activated protein kinases inhibitors.
AB  - Background/Aim: Currently, it has been proposed that combination of 5
      fluorouracil (5FU) with inhibitors of the mitogen-activated protein kinases
      (MAPKs) signaling pathway might enhance the efficacy of 5FU-based chemotherapy in
      colon cancer. Our study aimed to investigate an impact of TWIST1 silencing on the
      sensitivity of cancer cells to 5FU and selected MAPK inhibitors. Materials and
      Methods: The suppression of TWIST1 expression in human colon cancer HT29 and
      HCT116 cell lines was achieved by transduction with lentiviral vector carrying
      the TWIST1 silencing sequence (pLL3.7-sh TWIST1). The statistical calculation was
      performed with analysis of variance or Dunnett's test for comparison to control
      group. Paired Student's t-test was performed when two groups were analyzed.
      Results: Suppression of TWIST1 reduced the proliferation rate of colon cancer
      cells and enhanced their sensitivity to 5FU and MAPKs inhibitors. The sensitivity
      of HT29 cells to examined compounds was more dependent on TWIST1 expression level
      compared to HCT116 cells. The most noticeable effect of TWIST1 suppression on
      sensitivity of both colon cancer cell lines to combined treatment of 5FU and the
      MAPKs inhibitors was observed for inhibitors of p38alpha/beta and JNK1-3. We also
      noted that the suppression of TWIST1 significantly sensitized both cell lines to
      combined treatment of 5FU and Rac inhibitor. Conclusions: Our observations point
      to TWIST1 expression level as a marker of colon cancer sensitivity to combined
      treatment of 5FU and MAPKs inhibitors.

PMID- 29451184
TI  - The long-term outcomes of cirrhotic patients with pleural effusion.
AB  - Background/Aim: A pleural effusion is an abnormal collection of fluid in the
      pleural space and may cause related morbidity or mortality in cirrhotic patients.
      Currently, there are insufficient data to support the long-term prognosis for
      cirrhotic patients with pleural effusion. In this study, we investigated the
      short- and long-term effects of pleural effusion on mortality in cirrhotic
      patients and evaluated the benefit of liver transplantation in these patients.
      Patients and Methods: The National Health Insurance Database, derived from the
      Taiwan National Health Insurance Program, was used to identify 3,487 cirrhotic
      patients with pleural effusion requiring drainage between January 1, 2007 and
      December 31, 2010. The proportional hazards Cox regression model was used to
      control for possible confounding factors. Results: The 30-day, 90-day, 1-year,
      and 3-year mortalities were 20.1%, 40.2%, 59.1%, and 75.9%, respectively, in the
      cirrhotic patients with pleural effusion. After Cox proportional hazard
      regression analysis adjusted by patient gender, age, complications of cirrhosis
      and comorbid disorders, old age, esophageal variceal bleeding, hepatocellular
      carcinoma, hepatic encephalopathy, pneumonia, renal function impairment, and
      without liver transplantation conferred higher risks for 3-year mortality in the
      cirrhotic patients with pleura effusion. Liver transplantation is the most
      important factor to determine the 3-year mortalities (HR: 0.17, 95% CI 0.11-
      0.26, P < 0.001). The 30-day, 30 to 90-day, 90-day to 1-year, and 1 to 3-year
      mortalities were 5.7%, 13.4%, 20.4%, and 21.7% respectively, in the liver
      transplantation group, and 20.5%, 41.0%, 61.2%, and 77.5%, respectively, in the
      non-liver transplantation group. Conclusion: In cirrhotic patients, the presence
      of pleural effusion predicts poor long-term outcomes. Liver transplantation could
      dramatically improve the survival and should be suggested as soon as possible.

PMID- 29451185
TI  - Early versus conventional stoma closure following bowel surgery: A randomized
      controlled trial.
AB  - Background/Aim: To compare early stoma closure with conventional stoma closure
      following defunctioning diversion stoma surgery with respect to the frequency of
      complications, health-related quality of life (QoL), and length of
      hospitalization (LoH). Patients and Methods: This study was designed as a
      prospective parallel-arm randomized controlled trial. Patients who underwent
      temporary stoma following bowel surgery between February 2014 and November 2015
      were included. The rate of complications (medical and surgical) following early
      and conventional stoma closure was assessed. Health-related QoL and LoH were also
      measured. Results: One hundred patients were included, with 50 cases in each
      group. Postoperative complications including laparostoma (6% vs. 2%;P = 0.307),
      wound infection (32% vs. 18%; P = 0.106), intra-abdominal collection (14% vs.
      18%; P = 0.585), anastomotic leak (4%vs. 8%;P = 0.400), and medical complications
      were comparable (22% vs. 32%;P = 0.257). The length of hospital stay, overall
      mortality and morbidity (64% vs. 44%; P = 0.05) were similar across the two
      groups. There was a significant reduction in the cost towards stoma care (96% vs.
      2%; P = 0.001) in the early stoma closure group. Patients in the early stoma
      closure group also had a significantly better QoL. Conclusion: Early stoma
      closure does not carry an increased risk of postoperative complications, reduces
      cost towards stoma care, and leads to better a QoL.

PMID- 29451186
TI  - Lactobacillus acidophilus and Bifidobacterium longum supernatants upregulate the
      serotonin transporter expression in intestinal epithelial cells.
AB  - Background/Aims: Probiotics play a role in relieving irritable bowel syndrome
      (IBS); however, the underlying mechanism is yet unclear. The aim of the study was
      to investigate the effects of the supernatants of Lactobacillus acidophilus and
      Bifidobacterium longum on the expression of serotonin transporter (SERT)
      messenger ribonucleic acid (mRNA) and protein. Materials and Methods: HT-29 and
      Caco-2 cells were treated with different concentrations of L. acidophilus and B.
      longum supernatants for 12 h and 24 h, respectively. SERT mRNA and proteins
      levels were detected by real-time polymerase chain reaction (real-time PCR) and
      Western-blotting. Results: The mRNA levels of SERT in HT-29 and Caco-2 cells
      treated with different concentrations of L. acidophilus or B. longum supernatants
      for 12 h and 24 h, each, were higher than that in the control groups. In
      addition, the expression of the protein in both cells was also upregulated, which
      was approximately similar to that of the corresponding mRNA. Conclusions: L.
      acidophilus and B. longum supernatants can upregulate SERT mRNA and protein
      levels in intestinal epithelial cells.

PMID- 29451187
TI  - Common bile duct cannulation in the left lateral position during ERCP.

PMID- 29451188
TI  - Severe pneumatosis intestinalis with portal venous gas.

PMID- 29451189
TI  - Elimination of leprosy in India: An analysis.
AB  - India attained the elimination figure of less than 1 case of leprosy per 10,000
      people during December 2005. Despite this, India still accounts for the largest
      number of new leprosy cases in the world, maintaining more than 50 per cent of
      the leprosy burden of the world, notwithstanding over three decades of use of
      multidrug therapy. The present review analyzes the process of execution of the
      elimination program, identifies any lacunae therein and presents corrective
      measures that could be taken up for elimination of the disease from the country.

PMID- 29451190
TI  - Music box spine keratoderma.

PMID- 29451191
TI  - Actinomycotic osteomyelitis.

PMID- 29451192
TI  - Author reply.

PMID- 29451193
TI  - Clinical experience of adalimumab in the treatment of psoriasis - A 10-year
      journey in a tertiary dermatology centre.

PMID- 29451194
TI  - Calciphylaxis as cutaneous marker of hyperparathyroidism and successful outcome
      with parathyroidectomy followed by hyperbaric oxygen therapy.

PMID- 29451195
TI  - Disseminated herpes simplex virus and varicella zoster virus co-infection in an
      immunocompetent patient.

PMID- 29451196
TI  - Atypical generalized morphea-like scleroderma occurring in a patient exposed to
      organic solvents and having chronic hepatitis C virus infection.

PMID- 29451197
TI  - Erratum: Extranodal natural killer/T cell lymphoma, nasal type presenting as
      recurrent facial cellulitis.
AB  - [This corrects the article DOI: 10.4103/ijdvl.IJDVL_687_16.].

PMID- 29451198
TI  - Letter from the Editors-In-Chief.

PMID- 29451199
TI  - Brain injury and neural stem cells.
AB  - Many therapies with potential for treatment of brain injury have been
      investigated. Few types of cells have spurred as much interest and excitement as
      stem cells over the past few decades. The multipotentiality and self-renewing
      characteristics of stem cells confer upon them the capability to regenerate lost
      tissue in ischemic or degenerative conditions as well as trauma. While stem cells
      have not yet proven to be clinically effective in many such conditions as was
      once hoped, they have demonstrated some effects that could be manipulated for
      clinical benefit. The various types of stem cells have similar characteristics,
      and largely differ in terms of origin; those that have differentiated to some
      extent may exhibit limited capability in differentiation potential. Stem cells
      can aid in decreasing lesion size and improving function following brain injury.

PMID- 29451200
TI  - Modulation of mitochondrial bioenergetics as a therapeutic strategy in
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an increasingly pressing worldwide public-health,
      social, political and economic concern. Despite significant investment in
      multiple traditional therapeutic strategies that have achieved success in
      preclinical models addressing the pathological hallmarks of the disease, these
      efforts have not translated into any effective disease-modifying therapies. This
      could be because interventions are being tested too late in the disease process.
      While existing therapies provide symptomatic and clinical benefit, they do not
      fully address the molecular abnormalities that occur in AD neurons. The
      pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain
      hypometabolism coupled with increased mitochondrial oxidative stress are
      antecedent and potentially play a causal role in the disease pathogenesis.
      Dysfunctional mitochondria accumulate from the combination of impaired mitophagy,
      which can also induce injurious inflammatory responses, and inadequate neuronal
      mitochondrial biogenesis. Altering the metabolic capacity of the brain by
      modulating/potentiating its mitochondrial bioenergetics may be a strategy for
      disease prevention and treatment. We present insights into the mechanisms of
      mitochondrial dysfunction in AD brain as well as an overview of emerging
      treatments with the potential to prevent, delay or reverse the neurodegenerative
      process by targeting mitochondria.

PMID- 29451201
TI  - Tackling dipeptidyl peptidase IV in neurological disorders.
AB  - Dipeptidyl peptidase IV (DPP-IV) is a serine protease best known for its role in
      inactivating glucagon-like peptide-1 (GLP-1), pituitary adenylate cyclase
      activating polypeptide (PACAP) and glucose-dependent insulinotropic peptide
      (GIP), three stimulators of pancreatic insulin secretion with beneficial effects
      on glucose disposal. Owing to the relationship between DPP-IV and these peptides,
      inhibition of DPP-IV enzyme activity is considered as an attractive treatment
      option for diabetic patients. Nonetheless, increasing studies support the idea
      that DPP-IV might also be involved in the development of neurological disorders
      with a neuroinflammatory component, potentially through its non-incretin
      activities on immune cells. In this review article, we aim at highlighting recent
      literature describing the therapeutic value of DPP-IV inhibitors for the
      treatment of such neurological conditions. Finally, we will illustrate some of
      the promising results obtained using berberine, a plant extract with potent
      inhibitory activity on DPP-IV.

PMID- 29451202
TI  - Stem cells for spinal cord injuries bearing translational potential.
AB  - Spinal cord injury (SCI) is a highly debilitating neurological disease, which
      still lacks effective treatment strategies, causing significant financial burden
      and distress to the affected families. Nevertheless, nanotechnology and
      regenerative medicine strategies holding promise for the development of novel
      therapies that would reach from bench to bedside to serve the SCI patients. There
      has already been significant progress in the field of cell-based therapies, with
      the clinical application for SCI, currently in phase II of the clinical trial.
      Stem cells (e.g., induced pluripotent stem cells, fetal stem cells, human
      embryonic stem cells, and olfactory ensheathing cells) are certainly not to be
      considered the panacea for neural repair but, especially when combined with
      rehabilitation or other combinatorial approaches using the help of
      nanotechnology, they seem to be the source of some of the most promising and
      clinical translatable cell-based therapies that could help solving impactful
      problems on neural repair.

PMID- 29451204
TI  - Conundrums and confusions regarding how polyethylene glycol-fusion produces
      excellent behavioral recovery after peripheral nerve injuries.
AB  - Current Neuroscience dogma holds that transections or ablations of a segment of
      peripheral nerves produce: (1) Immediate loss of axonal continuity, sensory
      signaling, and motor control; (2) Wallerian rapid (1-3 days) degeneration of
      severed distal axons, muscle atrophy, and poor behavioral recovery after many
      months (if ever, after ablations) by slowly-regenerating (1 mm/d), proximal-stump
      outgrowths that must specifically reinnervate denervated targets; (3) Poor
      acceptance of microsutured nerve allografts, even if tissue-matched and immune
      suppressed. Repair of transections/ablations by neurorrhaphy and well-specified
      sequences of PEG-fusion solutions (one containing polyethylene glycol, PEG)
      successfully address these problems. However, conundrums and confusions regarding
      unorthodox and dramatic results of PEG-fusion repair in animal model systems
      often lead to misunderstandings. For example, (1) Axonal continuity and signaling
      is re-established within minutes by non-specifically PEG-fusing (connecting)
      severed motor and sensory axons across each lesion site, but remarkable
      behavioral recovery to near-unoperated levels takes several weeks; (2) Many
      distal stumps of inappropriately-reconnected, PEG-fused axons do not ever
      (Wallerian) degenerate and continuously innervate muscle fibers that undergo much
      less atrophy than otherwise-denervated muscle fibers; (3) Host rats do not reject
      PEG-fused donor nerve allografts in a non-immuno-privileged environment with no
      tissue matching or immunosuppression; (4) PEG fuses apposed open axonal ends or
      seals each shut (thereby preventing PEG-fusion), depending on the experimental
      protocol; (5) PEG-fusion protocols produce similar results in animal model
      systems and early human case studies. Hence, iconoclastic PEG-fusion data
      appropriately understood might provoke a re-thinking of some Neuroscience dogma
      and a paradigm shift in clinical treatment of peripheral nerve injuries.

PMID- 29451203
TI  - A growing field: The regulation of axonal regeneration by Wnt signaling.
AB  - The canonical Wnt/beta-catenin pathway is a highly conserved signaling cascade
      that plays critical roles during embryogenesis. Wnt ligands regulate axonal
      extension, growth cone guidance and synaptogenesis throughout the developing
      central nervous system (CNS). Recently, studies in mammalian and fish model
      systems have demonstrated that Wnt/beta-catenin signaling also promotes axonal
      regeneration in the adult optic nerve and spinal cord after injury, raising the
      possibility that Wnt could be developed as a therapeutic strategy. In this
      review, we summarize experimental evidence that reveals novel roles for Wnt
      signaling in the injured CNS, and discuss possible mechanisms by which Wnt
      ligands could overcome molecular barriers inhibiting axonal growth to promote
      regeneration. A central challenge in the neuroscience field is developing
      therapeutic strategies that induce robust axonal regeneration. Although adult
      axons have the capacity to respond to axonal guidance molecules after injury,
      there are several major obstacles for axonal growth, including extensive neuronal
      death, glial scars at the injury site, and lack of axonal guidance signals.
      Research in rodents demonstrated that activation of Wnt/beta-catenin signaling in
      retinal neurons and radial glia induced neuronal survival and axonal growth, but
      that activation within reactive glia at the injury site promoted proliferation
      and glial scar formation. Studies in zebrafish spinal cord injury models confirm
      an axonal regenerative role for Wnt/beta-catenin signaling and identified the
      cell types responsible. Additionally, in vitro and in vivo studies demonstrated
      that Wnt induces axonal and neurite growth through transcription-dependent
      effects of its central mediator beta-catenin, potentially by inducing
      regeneration-promoting genes. Canonical Wnt signaling may also function through
      transcription-independent interactions of beta-catenin with cytoskeletal
      elements, which could stabilize growing axons and control growth cone movement.
      Therefore, these studies suggest that Wnt-induced pathways responsible for
      regulating axonal growth during embryogenesis could be repurposed to promote
      axonal growth after injury.

PMID- 29451206
TI  - Screening antioxidants for the protection of cochlear sensory cells.

PMID- 29451205
TI  - Optical read-out and modulation of peripheral nerve activity.
AB  - Numerous clinical and research applications necessitate the ability to interface
      with peripheral nerve fibers to read and control relevant neural pathways.
      Visceral organ modulation and rehabilitative prosthesis are two areas which could
      benefit greatly from improved neural interfacing approaches. Therapeutic neural
      interfacing, or 'bioelectronic medicine', has potential to affect a broad range
      of disorders given that all the major organs of the viscera are neurally
      innervated. However, a better understanding of the neural pathways that underlie
      function and a means to precisely interface with these fibers are required.
      Existing peripheral nerve interfaces, consisting primarily of electrode-based
      designs, are unsuited for highly specific (individual axon) communication and/or
      are invasive to the tissue. Our laboratory has explored an optogenetic approach
      by which optically sensitive reporters and actuators are targeted to specific
      cell (axon) types. The nature of such an approach is laid out in this short
      perspective, along with associated technologies and challenges.

PMID- 29451207
TI  - Diabetes, its impact on peripheral nerve regeneration: lessons from pre-clinical
      rat models towards nerve repair and reconstruction.

PMID- 29451208
TI  - Astrocytes in the cerebral cortex play a role in the spontaneous motor recovery
      following experimental striatal hemorrhage.

PMID- 29451209
TI  - Predictors of short-term outcome in patients with acute middle cerebral artery
      occlusion: unsuitability of fluid-attenuated inversion recovery vascular
      hyperintensity scores.
AB  - Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) is used
      to assess leptomeningeal collateral circulation, but clinical outcomes of
      patients with FVH can be very different. The aim of the present study was to
      assess a FVH score and explore its relationship with clinical outcomes. Patients
      with acute ischemic stroke due to middle cerebral artery M1 occlusion underwent
      magnetic resonance imaging and were followed up at 10 days (National Institutes
      of Health Stroke Scale) and 90 days (modified Rankin Scale) to determine short
      term clinical outcomes. Effective collateral circulation indirectly improved
      recovery of neurological function and short-term clinical outcome by extending
      the size of the pial penumbra and reducing infarct lesions. FVH score showed no
      correlation with 90-day functional clinical outcome and was not sufficient as an
      independent predictor of short-term clinical outcome.

PMID- 29451210
TI  - Intravenous morphine self-administration alters accumbal microRNA profiles in the
      mouse brain.
AB  - A significant amount of evidence indicates that microRNAs (miRNAs) play an
      important role in drug addiction. The nucleus accumbens (NAc) is a critical part
      of the brain's reward circuit and is involved in a variety of psychiatric
      disorders, including depression, anxiety, and drug addiction. However, few
      studies have examined the expression of miRNAs and their functional roles in the
      NAc under conditions of morphine addiction. In this study, mice were
      intravenously infused with morphine (0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion) and
      showed inverted U-shaped response. After morphine self-administration, NAc was
      used to analyze the functional networks of altered miRNAs and their putative
      target mRNAs in the NAc following intravenous self-administration of morphine. We
      utilized several bioinformatics tools, including Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathway mapping and CyTargetLinker. We found that 62 miRNAs were
      altered and exhibited differential expression patterns. The putative targets were
      related to diverse regulatory functions, such as neurogenesis, neurodegeneration,
      and synaptic plasticity, as well as the pharmacological effects of morphine
      (receptor internalization/endocytosis). The present findings provide novel
      insights into the regulatory mechanisms of accumbal molecules under conditions of
      morphine addiction and identify several novel biomarkers associated with morphine
      addiction.

PMID- 29451211
TI  - Electroacupuncture preconditioning protects against focal cerebral
      ischemia/reperfusion injury via suppression of dynamin-related protein 1.
AB  - Electroacupuncture preconditioning at acupoint Baihui (GV20) can reduce focal
      cerebral ischemia/reperfusion injury. However, the precise protective mechanism
      remains unknown. Mitochondrial fission mediated by dynamin-related protein 1
      (Drp1) can trigger neuronal apoptosis following cerebral ischemia/reperfusion
      injury. Herein, we examined the hypothesis that electroacupuncture pretreatment
      can regulate Drp1, and thus inhibit mitochondrial fission to provide cerebral
      protection. Rat models of focal cerebral ischemia/reperfusion injury were
      established by middle cerebral artery occlusion at 24 hours after 5 consecutive
      days of preconditioning with electroacupuncture at GV20 (depth 2 mm, intensity 1
      mA, frequency 2/15 Hz, for 30 minutes, once a day). Neurological function was
      assessed using the Longa neurological deficit score. Pathological changes in the
      ischemic penumbra on the injury side were assessed by hematoxylin-eosin staining.
      Cellular apoptosis in the ischemic penumbra on the injury side was assessed by
      terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end
      labeling staining. Mitochondrial ultrastructure in the ischemic penumbra on the
      injury side was assessed by transmission electron microscopy. Drp1 and cytochrome
      c expression in the ischemic penumbra on the injury side were assessed by western
      blot assay. Results showed that electroacupuncture preconditioning decreased
      expression of total and mitochondrial Drp1, decreased expression of total and
      cytosolic cytochrome c, maintained mitochondrial morphology and reduced the
      proportion of apoptotic cells in the ischemic penumbra on the injury side, with
      associated improvements in neurological function. These data suggest that
      electroacupuncture preconditioning-induced neuronal protection involves
      inhibition of the expression and translocation of Drp1.

PMID- 29451212
TI  - Is it necessary to use the entire root as a donor when transferring contralateral
      C7 nerve to repair median nerve?
AB  - If a partial contralateral C7 nerve is transferred to a recipient injured nerve,
      results are not satisfactory. However, if an entire contralateral C7 nerve is
      used to repair two nerves, both recipient nerves show good recovery. These
      findings seem contradictory, as the above two methods use the same donor nerve,
      only the cutting method of the contralateral C7 nerve is different. To verify
      whether this can actually result in different repair effects, we divided rats
      with right total brachial plexus injury into three groups. In the entire root
      group, the entire contralateral C7 root was transected and transferred to the
      median nerve of the affected limb. In the posterior division group, only the
      posterior division of the contralateral C7 root was transected and transferred to
      the median nerve. In the entire root + posterior division group, the entire
      contralateral C7 root was transected but only the posterior division was
      transferred to the median nerve. After neurectomy, the median nerve was repaired
      on the affected side in the three groups. At 8, 12, and 16 weeks postoperatively,
      electrophysiological examination showed that maximum amplitude, latency, muscle
      tetanic contraction force, and muscle fiber cross-sectional area of the flexor
      digitorum superficialis muscle were significantly better in the entire root and
      entire root + posterior division groups than in the posterior division group. No
      significant difference was found between the entire root and entire root +
      posterior division groups. Counts of myelinated axons in the median nerve were
      greater in the entire root group than in the entire root + posterior division
      group, which were greater than the posterior division group. We conclude that for
      the same recipient nerve, harvesting of the entire contralateral C7 root achieved
      significantly better recovery than partial harvesting, even if only part of the
      entire root was used for transfer. This result indicates that the entire root
      should be used as a donor when transferring contralateral C7 nerve.

PMID- 29451213
TI  - Bone marrow-derived mesenchymal stem cells versus adipose-derived mesenchymal
      stem cells for peripheral nerve regeneration.
AB  - Studies have confirmed that bone marrow-derived mesenchymal stem cells (MSCs) can
      be used for treatment of several nervous system diseases. However, isolation of
      bone marrow-derived MSCs (BMSCs) is an invasive and painful process and the yield
      is very low. Therefore, there is a need to search for other alterative stem cell
      sources. Adipose-derived MSCs (ADSCs) have phenotypic and gene expression
      profiles similar to those of BMSCs. The production of ADSCs is greater than that
      of BMSCs, and ADSCs proliferate faster than BMSCs. To compare the effects of
      venous grafts containing BMSCs or ADSCs on sciatic nerve injury, in this study,
      rats were randomly divided into four groups: sham (only sciatic nerve exposed),
      Matrigel (MG; sciatic nerve injury + intravenous transplantation of MG vehicle),
      ADSCs (sciatic nerve injury + intravenous MG containing ADSCs), and BMSCs
      (sciatic nerve injury + intravenous MG containing BMSCs) groups. Sciatic
      functional index was calculated to evaluate the function of injured sciatic
      nerve. Morphologic characteristics of nerves distal to the lesion were observed
      by toluidine blue staining. Spinal motor neurons labeled with Fluoro-Gold were
      quantitatively assessed. Compared with sham-operated rats, sciatic functional
      index was lower, the density of small-diameter fibers was significantly
      increased, and the number of motor neurons significantly decreased in rats with
      sciatic nerve injury. Neither ADSCs nor BMSCs significantly improved the sciatic
      nerve function of rats with sciatic nerve injury, increased fiber density, fiber
      diameters, axonal diameters, myelin sheath thickness, and G ratios (axonal
      diameter/fiber diameter ratios) in the sciatic nerve distal to the lesion site.
      There was no significant difference in the number of spinal motor neurons among
      ADSCs, BMSCs and MG groups. These results suggest that neither BMSCs nor ADSCs
      provide satisfactory results for peripheral nerve repair when using MG as the
      conductor for engraftment.

PMID- 29451214
TI  - Optimization of micropatterned poly(lactic-co-glycolic acid) films for enhancing
      dorsal root ganglion cell orientation and extension.
AB  - Nerve conduits have been a viable alternative to the 'gold standard' autograft
      for treating small peripheral nerve gap injuries. However, they often produce
      inadequate functional recovery outcomes and are ineffective in large gap
      injuries. Ridge/groove surface micropatterning has been shown to promote neural
      cell orientation and guide growth. However, optimization of the ratio of
      ridge/groove parameters to promote orientation and extension for dorsal root
      ganglion (DRG) cells on poly(lactic-co-glycolic acid) (PLGA) films has not been
      previously conducted. Photolithography and micro-molding were used to define
      various combinations of ridge/groove dimensions on PLGA films. The DRG cells
      obtained from chicken embryos were cultured on micropatterned PLGA films for cell
      orientation and migration evaluation. Biodegradation of the films occurred during
      the test period, however, this did not cause deformation or distortion of the
      micropatterns. Results from the DRG cell orientation test suggest that when the
      ridge/groove ratio equals 1 (ridge/groove width parameters are equal, i.e., 10
      MUm/10 MUm (even)), the degree of alignment depends on the size of the ridges and
      grooves, when the ratio is smaller than 1 (groove controlled) the alignment
      increases as the ridge size decreases, and when the ratio is larger than 1 (ridge
      controlled), the alignment is reduced as the width of the grooves decreases. The
      migration rate and neurite extension of DRG neurons were greatest on 10 MUm/10
      MUm and 30 MUm/30 MUm micropatterned PLGA films. Based on the data, the 10 MUm/10
      MUm and 30 MUm/30 MUm micropatterned PLGA films are the optimized ridge/groove
      surface patterns for the construction of nerve repair devices.

PMID- 29451215
TI  - Effect of moxibustion on mTOR-mediated autophagy in rotenone-induced Parkinson's
      disease model rats.
AB  - Defects in autophagy-mediated clearance of alpha-synuclein may be one of the key
      factors leading to progressive loss of dopaminergic neurons in the substantia
      nigra. Moxibustion therapy for Parkinson's disease has been shown to have a
      positive effect, but the underlying mechanism remains unknown. Based on this, we
      explored whether moxibustion could protect dopaminergic neurons by promoting
      autophagy mediated by mammalian target of rapamycin (mTOR), with subsequent
      elimination of alpha-syn. A Parkinson's disease model was induced in rats by
      subcutaneous injection of rotenone at the back of their necks, and they received
      moxibustion at Zusanli (ST36), Guanyuan (CV4) and Fengfu (GV16), for 10 minutes
      at every point, once per day, for 14 consecutive days. Model rats without any
      treatment were used as a sham control. Compared with the Parkinson's disease
      group, the moxibustion group showed significantly greater tyrosine hydroxylase
      immunoreactivity and expression of light chain 3-II protein in the substantia
      nigra, and their behavioral score, alpha-synuclein immunoreactivity, the
      expression of phosphorylated mTOR and phosphorylated ribosomal protein S6 kinase
      (p-p70S6K) in the substantia nigra were significantly lower. These results
      suggest that moxibustion can promote the autophagic clearance of alpha-syn and
      improve behavioral performance in Parkinson's disease model rats. The protective
      mechanism may be associated with suppression of the mTOR/p70S6K pathway.

PMID- 29451216
TI  - Does combined therapy of curcumin and epigallocatechin gallate have a synergistic
      neuroprotective effect against spinal cord injury?
AB  - Systematic inflammatory response after spinal cord injury (SCI) is one of the
      factors leading to lesion development and a profound degree of functional loss.
      Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG)
      are known for their neuroprotective effects. In this study, we investigated the
      effect of combined therapy of curcumin and EGCG in a rat model of acute SCI
      induced by balloon compression. Immediately after SCI, rats received curcumin,
      EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg;
      EGCG 17 mg/kg)] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17
      mg/kg)] for 28 days. Rats were evaluated using behavioral tests (the Basso,
      Beattie, and Bresnahan (BBB) open-field locomotor test, flat beam test). Spinal
      cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet
      staining) and immunohistochemistry (anti-glial fibrillary acidic protein, anti
      growth associated protein 43). Cytokine levels (interleukin-1beta, interleukin-4,
      interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and
      RANTES) were measured using Luminex assay. Quantitative polymerase chain reaction
      was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5,
      Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfkappaB, Cntf) related to regenerative
      processes in injured spinal cord. We found that all treatments displayed
      significant behavioral recovery, with no obvious synergistic effect after
      combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination
      increased axonal sprouting, decreased glial scar formation, and altered the
      levels of macrophage inflammatory protein 1-alpha, interleukin-1beta, interleukin
      4 and interleukin-6 cytokines. These results imply that although the expected
      synergistic response of this combined therapy was less obvious, aspects of tissue
      regeneration and immune responses in severe SCI were evident.

PMID- 29451217
TI  - Neuroprotective mechanisms of rutin for spinal cord injury through anti-oxidation
      and anti-inflammation and inhibition of p38 mitogen activated protein kinase
      pathway.
AB  - Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune
      regulatory effects. However, the neuroprotective effects of rutin in spinal cord
      injury are unknown. The p38 mitogen activated protein kinase (p38 MAPK) pathway
      is the most important member of the MAPK family that controls inflammation. We
      assumed that the mechanism of rutin in the repair of spinal cord injury is
      associated with the inhibition of p38 MAPK pathway. Allen's method was used to
      establish a rat model of spinal cord injury. The rat model was intraperitoneally
      injected with rutin (30 mg/kg) for 3 days. After treatment with rutin, Basso,
      Beattie and Bresnahan locomotor function scores increased. Water content, tumor
      necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK
      protein expression and caspase-3 and -9 activities in T8-9 spinal cord decreased.
      Oxidative stress related markers superoxide dismutase and glutathione peroxidase
      levels increased in peripheral blood. Rutin exerts neuroprotective effect through
      anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK
      pathway.

PMID- 29451218
TI  - PTEN knockdown with the Y444F mutant AAV2 vector promotes axonal regeneration in
      the adult optic nerve.
AB  - The lack of axonal regeneration is the major cause of vision loss after optic
      nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has
      been shown to enhance the intrinsic growth capacity of neurons and to facilitate
      axonal regeneration in the central nervous system after injury. The deletion of
      the mTOR negative regulator phosphatase and tensin homolog (PTEN) enhances
      regeneration of adult corticospinal neurons and ganglion cells. In the present
      study, we used a tyrosine-mutated (Y444F) AAV2 vector to efficiently express a
      short hairpin RNA (shRNA) for silencing PTEN expression in retinal ganglion
      cells. We evaluated cell survival and axonal regeneration in a rat model of optic
      nerve axotomy. The rats received an intravitreal injection of wildtype AAV2 or
      Y444F mutant AAV2 (both carrying shRNA to PTEN) 4 weeks before optic nerve
      axotomy. Compared with the wildtype AAV2 vector, the Y444F mutant AAV2 vector
      enhanced retinal ganglia cell survival and stimulated axonal regeneration to a
      greater extent 6 weeks after axotomy. Moreover, post-axotomy injection of the
      Y444F AAV2 vector expressing the shRNA to PTEN rescued ~19% of retinal ganglion
      cells and induced axons to regenerate near to the optic chiasm. Taken together,
      our results demonstrate that PTEN knockdown with the Y444F AAV2 vector promotes
      retinal ganglion cell survival and stimulates long-distance axonal regeneration
      after optic nerve axotomy. Therefore, the Y444F AAV2 vector might be a promising
      gene therapy tool for treating optic nerve injury.

PMID- 29451221
TI  - Correction: Autologous transplantation with fewer fibers repairs large peripheral
      nerve defects.

PMID- 29451219
TI  - Low-frequency pulsed electromagnetic field pretreated bone marrow-derived
      mesenchymal stem cells promote the regeneration of crush-injured rat mental
      nerve.
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to promote the
      regeneration of injured peripheral nerves. Pulsed electromagnetic field (PEMF)
      reportedly promotes the proliferation and neuronal differentiation of BMSCs. Low
      frequency PEMF can induce the neuronal differentiation of BMSCs in the absence of
      nerve growth factors. This study was designed to investigate the effects of low
      frequency PEMF pretreatment on the proliferation and function of BMSCs and the
      effects of low-frequency PEMF pre-treated BMSCs on the regeneration of injured
      peripheral nerve using in vitro and in vivo experiments. In in vitro experiments,
      quantitative DNA analysis was performed to determine the proliferation of BMSCs,
      and reverse transcription-polymerase chain reaction was performed to detect S100
      (Schwann cell marker), glial fibrillary acidic protein (astrocyte marker), and
      brain-derived neurotrophic factor and nerve growth factor (neurotrophic factors)
      mRNA expression. In the in vivo experiments, rat models of crush-injured mental
      nerve established using clamp method were randomly injected with low-frequency
      PEMF pretreated BMSCs, unpretreated BMSCs or PBS at the injury site (1 * 106
      cells). DiI-labeled BMSCs injected at the injury site were counted under the
      fluorescence microscope to determine cell survival. One or two weeks after cell
      injection, functional recovery of the injured nerve was assessed using the
      sensory test with von Frey filaments. Two weeks after cell injection, axonal
      regeneration was evaluated using histomorphometric analysis and retrograde
      labeling of trigeminal ganglion neurons. In vitro experiment results revealed
      that low-frequency PEMF pretreated BMSCs proliferated faster and had greater mRNA
      expression of growth factors than unpretreated BMSCs. In vivo experiment results
      revealed that compared with injection of unpretreated BMSCs, injection of low
      frequency PEMF pretreated BMSCs led to higher myelinated axon count and axon
      density and more DiI-labeled neurons in the trigeminal ganglia, contributing to
      rapider functional recovery of injured mental nerve. These findings suggest that
      low-frequency PEMF pretreatment is a promising approach to enhance the efficacy
      of cell therapy for peripheral nerve injury repair.

PMID- 29451220
TI  - Critical role of SDF-1/CXCR4 signaling pathway in stem cell homing in the
      deafened rat cochlea after acoustic trauma.
AB  - Previous animal studies have shown that stromal cell-derived factor-1 (SDF-1)/CXC
      chemokine receptor-4 (CXCR4) signaling pathway plays an important role in the
      targeted migration of bone marrow-derived mesenchymal stem cells (BMSCs) to the
      injured area. In the present study, we aimed to investigate the potential role of
      chemotactic SDF-1/CXCR4 signaling pathway in the homing of transplanted BMSCs to
      the injured cochlea after noise-induced hearing loss (NIHL) in a rat model. White
      noise exposure (110 dB) paradigm was used for hearing loss induction in male rats
      for 6 hours in 5 days. Distortion-product otoacoustic emission (DPOAE) responses
      were recorded before the experiment and post noise exposure. Hoechst 33342
      labeled BMSCs and CXCR4 antagonist (AMD3100)-treated BMSCs were injected into the
      rat cochlea through the round window. SDF-1 protein expression in the cochlear
      tissue was assayed using western blot assay. The number of labeled BMSCs reaching
      the endolymph was determined after 24 hours. SDF-1 was significantly increased in
      the cochlear tissue of rats in the noise exposure group than in the control
      group. The number of Hoechst 33342-labeled BMSCs reaching the endolymph of the
      cochlea was significantly smaller in the AMD3100-treated BMSCs group than in the
      normal BMSCs group. Our present findings suggest that the SDF-1/CXCR4 signaling
      pathway has a critical role in BMSCs migration to the injured cochlea in a rat
      model of noise-induced hearing loss.

PMID- 29451222
TI  - Injury of the Papez circuit in a patient with traumatic spinal cord injury and
      concomitant mild traumatic brain injury.

PMID- 29451223
TI  - Multidisciplinary care of haemoglobinopathies in Qatar.
AB  - Not available.

PMID- 29451224
TI  - Hypogonadism in male thalassemia major patients: pathophysiology, diagnosis and
      treatment.
AB  - Failure of pubertal growth, delay or absence of sexual development, infertility
      and sexual dysfunction due to hypogonadism and defective spermatogenesis are
      frequent and well recognized disturbances among male patients with transfusion
      dependent (TD) thalassaemia major (beta-thal). These problems are attributed
      mainly to the damage caused by chronic anaemia and the deposition of excess iron
      in the pituitary gland and testicles. This is a short review of male pubertal
      disorders in patients with beta-thal written by pediatric endocrinologists and
      haematologists with an interest and active involvement, in the diagnosis and
      management of these complications in this group of patients. A vigilant clinical
      evaluation of growth and puberty, as well as an appropriate hormonal evaluation
      in poly-transfused (TD beta-thal) patients is strongly recommended for early
      detection and treatment of endocrine dysfunction. Of crucial importance also, is
      the implementation of an efficient chelation regime from early life, to prevent
      severe iron load and permanent damage to the endocrine glands, particularly those
      responsible for gonadal function.

PMID- 29451225
TI  - Quality of life among adolescents aged 14 to 18 years with Beta-Thalassemia Major
      (TM) in Qatar.
AB  - BACKGROUND: Thalassemia  is a heterogeneous group of inherited disorders of
      hemoglobin synthesis. It is a common disease in Mediterranean, Southeast Asia,
      Indian subcontinent, and Middle East countries, including Qatar. PURPOSE: The aim
      of this study was to assess the quality of life (QOL) among patients aged 14 to
      18 years with thalassemia major (TM) in Qatar and correlates their QOL with bio
      demographic data of the patients compared to healthy controls. MATERIALS AND
      METHODS: This cross-sectional study measured the QOL in adolescents with
      thalassemia major who were attending ambulatory units in a tertiary hospital in
      Qatar. Forty children and adolescents with TM and 40 healthy participants were
      enrolled in the study. Forty-two (52.5%) participants were males and 38 (47.5%)
      females. Data were collected utilizing PedsQLTM 4.0 generic core scale and were
      analyzed using the appropriate statistical method. RESULTS: Children with TM had
      significantly lower and more variable overall quality of life score (69.1 +/-
      16.8) compared to healthy matched children (77 +/- 12.8), (p <0.001). Both groups
      were not different from the physical, emotional, and social domains. Thalassemic 
      adolescents had also a significantly lower school performance. CONCLUSIONS: TM
      adversely affects the QOL of children and adolescents and this necessitates
      applying more efforts to help them improve and achieve a desirable quality of
      life. Patients with TM need more attention in schools that can be accomplished by
      implementing a special program for their management that needs a mutual
      collaboration between Ministry of Public Health (MoPH) and Ministry of Education
      (MoE) in Qatar.

PMID- 29451226
TI  - Final adult height and endocrine complications in young adults with beta
      thalassemia major (TM) who received oral iron chelation (OIC) in comparison with
      those who did not use OIC.
AB  - BACKGROUND: Relatively little is known about endocrine function, bone mineral
      health, and growth during oral iron chelation therapy in beta-thalassemia major
      patients (TM) on treatment with deferasirox. AIMS OF THE STUDY: To study the
      frequency of endocrine complications, IGF-1 levels and final adult standing
      height (FA-Ht) in patients with BTM in two groups of adult patients. PATIENTS AND
      METHODS: The first group (Group A; 15 patients, 6 females and 9 males) received
      oral iron chelation therapy (OIC) with deferasirox for 6 years before puberty;
      the second group (Group B;40 patients) attained the FA-Ht before the use of OIC
      (iron chelation therapy with deferoxamine (DFO) given subcutaneously, since the
      age of 2 years). In both groups liver iron concentration was measured using
      FerriScan (r) R2-MRI method. Furthermore, the FA-Ht, bode mass index (BMI), and
      insulin growth factor-1 (IGF-1) in a selected group of adult patients [9 with
      normal growth hormone (GH) secretion (GHN) and 8 with GH deficiency (GHD; peak GH
      response to provocative test  with clonidine: < 7 ng/ml), who were on iron
      chelation therapy with DFO given subcutaneously that was changed to oral
      deferasirox during the last 5-6 years. These 15 patients were not treated with
      rhGH. RESULTS: Adults with BTM who received OIC for 6 years or more before
      attaining their FA-Ht, had lower liver iron concentration (LIC) assessed by
      FerriScan(r) R2-MRI, fasting glucose level (FBG) and liver enzymes (ALT and AST),
      and a better FA-Ht expressed in standard deviation score (FA-Ht-SDS), and higher
      IGF-1 SDS versus those who did not receive OIC before attaining FA-Ht. The
      prevalence of endocrinopathies, including hypothyroidism and hypogonadism were
      significantly lower in Group A versus Group B.  Comparison between the group with
      normal GHN and those with GHD showed that the FA-Ht-SDS of those with GHD
      (159.1+/- 6.42 cm). Ht-SDS = -2.5 +/- 0.9) was significantly decreased compared
      to the group with NGH (Ht = 163.5 +/- 5.2 cm, Ht-SDS = -1.74 +/- 0.83).  The IGF
      1-SDS did not differ between the two groups. Neither ferritin level nor IGF-1
      concentrations were correlated with the Ht-SDS. The final FA-Ht-SDS correlated
      significantly with the peak GH secretion (r = 0.788, p = 0.0008). The FA-Ht-SDS
      were positively related to their mid-parental height (r=0.58, P <0.01).
      CONCLUSIONS: The use of OIC years before the end of puberty was associated with a
      significantly lower prevalence of endocrinopathies, improvement of LIC and FA-Ht.
      The final adult height of patients with BTM and GHD was significantly shorter
      compared to their pears with NGH. rhGH therapy can be recommended for the
      treatment of thalassemic children and adolescents with GHD in addition to proper
      blood transfusion and intensive chelation to improve their final height.

PMID- 29451227
TI  - Statural Growth and Prevalence of Endocrinopathies in Relation to Liver Iron
      Content (LIC) in Adult Patients with Beta Thalassemia Major (BTM) and Sickle Cell
      Disease (SCD).
AB  - Despite regular blood transfusion and iron chelation therapy, growth impairment
      and pubertal delay are commonly seen in children and adolescents with transfusion
      dependent Beta thalassaemia major (BTM) and sickle cell disease (SCD). We
      evaluated growth parameters and endocrine disorders in relation to the liver iron
      concentration (LIC) assessed by the Ferriscan(r) method in a cohort of adults
      with SCD (n =40) and BTM (n = 52) receiving blood transfusions and iron chelation
      therapy since early childhood. Before transfusion, hemoglobin concentration had
      not been less than 9 g/dl in the past 12 years; subcutaneous daily
      desferrioxamine was administered for all of them since early childhood (2- 5
      years of age). All patients were shifted to oral therapy with deferasirox iron
      chelation, 20 mg/daily for the past 5 years. BTM patients with higher LIC (> 15
      mg Fe/g dry weight)  had significantly shorter stature, lower insulin-like growth
      factor-I SDS (IGF-I SDS), higher alanine transferase (ALT) and  serum ferritin
      concentrations compared to thalassemic patients with lower LIC.  Patients with
      SCD with LIC > 8 mg Fe/g dry weight had significantly shorter stature, lower IGF
      I SDS and higher ALT compared to SCD patients with lower LIC.  Patients with BTM
      had significantly shorted final height (Ht-SDS) , IGF-I SDS and FT4 level
      compared to patients with SCD.  LIC and mean fasting blood glucose (FBG) were
      significantly higher in patients with BTM compared to those with SCD. The linear
      regression  analysis showed  a significant correlation between LIC and  serum
      ferritin level in SCD and BTM. LIC and serum ferritin level were also correlated
      significantly with IGF-I level in patients with BTM. LIC was correlated
      significantly with ALT in patients with BTM. In conclusion, the prevalence of
      endocrinopathies especially hypothyroidism, DM, and hypogonadism were
      significantly higher in BTM patients versus SCD patients and higher in patients
      with higher LIC versus those with lower LIC. These complications occurred less
      frequently, but still considerable, in chronically transfused patients with SCD.

PMID- 29451228
TI  - A persistent cough as atypical clinical presentation of intrathoracic
      extramedullary hematopoiesis (EMH) in a female with thalassemia intermedia.
AB  - Extramedullary hematopoiesis (EMH) is a rare disorder, defined as the appearance
      of hematopoietic elements outside the bone marrow or peripheral blood. The most
      common sites of EMH are liver and spleen, but it has been documented in other
      organs such as the mediastinum, lymph nodes, breast, and central nervous system.
      EMH occurs as a compensatory mechanism for bone marrow dysfunction in severe
      thalassemia. We report a case of EMH presenting as a posterior mediastinal mass
      in a 34-year-old woman with thalassemia intermedia with chronic cough and
      shortness of breath on exertion. The diagnosis of EMH was confirmed by a CT
      guided fine needle biopsy. All symptoms disappeared after surgical removal of the
      mass.

PMID- 29451231
TI  - Electron microscopy at the limits.

PMID- 29451230
TI  - Corrigendum: Dynamics of supersonic microparticle impact on elastomers revealed
      by real-time multi-frame imaging.
AB  - This corrects the article DOI: 10.1038/srep25577.

PMID- 29451232
TI  - Peralkaline volcanicity on the Eurasia Basin margin.
AB  - The Kap Washington Group of post-Palaeozoic explosive volcanic rocks was
      discovered in 1969 on the north coast of Greenland. Although there have been
      uncertainties regarding their age and chemical character, they have featured
      prominently in geotectonic reconstructions of the Arctic regions-in recent
      interpretations as products of the Yermak hot spot, generated on the Nansen
      spreading axis during the opening of the Eurasia Basin. We present here new
      evidence which confirms the volcanicity as end-Cretaceous in age and of
      peralkaline type. We show that a direct connection with the Yermak hot spot is
      improbable and infer that the volcanic rocks were generated in a continental
      extensional rift environment before the break-up of the Laurasian plate in the
      Arctic. Their age helps to constrain the timing of this poorly understood event.

PMID- 29451229
TI  - m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration.
AB  - The function of mitochondria depends on ubiquitously expressed and evolutionary
      conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases
      form hexameric complexes built up of homologous subunits. AFG3L2 subunits
      assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin)
      subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are
      associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss
      of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary
      spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being
      predominantly affected. Pleiotropic functions have been assigned to m-AAA
      proteases, which act as quality control and regulatory enzymes in mitochondria.
      Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration
      and leads to mitochondrial fragmentation and deficiencies in the axonal transport
      of mitochondria. Moreover m-AAA proteases regulate the assembly of the
      mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU
      subunit EMRE in AFG3L2-deficient mitochondria results in the formation of
      deregulated MCU complexes, increased mitochondrial calcium uptake and increased
      vulnerability of neurons for calcium-induced cell death. A reduction of calcium
      influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient
      mouse model. In this review, we discuss the relationship between the m-AAA
      protease and mitochondrial calcium homeostasis and its relevance for
      neurodegeneration and describe a novel mouse model lacking MCU specifically in
      Purkinje cells. Our results pledge for a novel view on m-AAA proteases that
      integrates their pleiotropic functions in mitochondria to explain the
      pathogenesis of associated neurodegenerative disorders.

PMID- 29451233
TI  - Migration of late Cenozoic volcanism in the South Island of New Zealand and the
      Campbell Plateau.
AB  - In late Cenozoic volcanics of eastern Australia, Wellman and McDougall1 have
      shown a remarkable southward migration pattern of major shield volcanoes of
      alkaline olivine basalt association which they relate to movement of the
      continental crust over a fixed mantle hot-spot. Contemporaneous tholeiite lava
      field provinces do not show a similar pattern. Following their general selection
      criteria1, I believe a similar situation emerges for New Zealand examples. In the
      South Island of New Zealand and the adjacent Campbell Plateau and Chatham Rise
      are several late Cenozoic volcanic centres that rest on a peneplain in Mesozoic
      and Palaeozoic granites and metamorphic rocks2,3, which is partly mantled by late
      Cretaceous to mid-Tertiary shallow marine sediments4,5. These major centres of
      late Cenozoic alkalic volcanism show an eastward decrease in age from ~28 Myr to
      ~0.5 Myr, presumably reflecting movement of a linear mantle source with respect
      to the Pacific Plate.

PMID- 29451235
TI  - New man in.

PMID- 29451234
TI  - The 26.13 MHz absorption line in the direction of Cassiopeia A.
AB  - It has recently been suggested1 that the absorption line v = 26.13 MHz that we
      had detected2 in the direction of Cassiopeia A might be a recombination line due
      either to carbon (C631alpha) present in H I clouds or to heavier elements of hot
      gas. Observations reported here taken in February 1981 suggest that the low
      frequency attenuation in the spectrum of Cas A is due to the presence of a cold
      cloud of ionized carbon.

PMID- 29451236
TI  - Rules for chemical reactions.

PMID- 29451237
TI  - 40Ar/39Ar age spectra from the KBS Tuff, Koobi Fora Formation.
AB  - 40Ar/39Ar age spectra on anorthoclase phenocrysts from three pumice clasts in the
      KBS Tuff yield nearly ideal flat patterns, providing good evidence that the
      samples have remained undisturbed since crystallization. The ages are concordant
      at 1.88+/-0.02 Myr, and confirm that the KBS Tuff, a key marker bed in the Koobi
      Fora Formation, northern Kenya, is now very well dated. These results resolve the
      conflict between earlier 40Ar/39Ar and conventional K-Ar dating measurements on
      the KBS Tuff.

PMID- 29451238
TI  - UK universities plan to fire staff.

PMID- 29451240
TI  - Fish-heads and breadcrumbs to feed the five thousand.

PMID- 29451239
TI  - Contradictions in theoretical chemistry.

PMID- 29451241
TI  - Shallowing-upward cycles in the Middle Proterozoic Altyn Formation.
AB  - Phanerozoic carbonate rocks commonly contain cycles, a few metres thick, which
      were deposited during progressive shallowing of their oceanic environment1. Each
      cycle represents a deepening of water in a nearshore area, followed by the
      accumulation of sediments up to sea level. The causes of the water deepening
      which begins each cycle are rarely known. Possibilities include tectonic activity
      that affected the depositional basin and changes in ocean volume due to the
      expansion and contraction of ice sheets. I report here that similar cycles occur
      in the Middle Proterozoic Altyn Formation, part of the Belt Supergroup2. The
      cycles are probably related to vertical tectonic activity which influenced
      sedimentation in the Belt basin. The presence of shallowing-upward cycles in the
      Altyn Formation shows that such cycles are not confined to the Phanerozoic. Other
      Precambrian sequences should be examined to see if they too contain cycles. Where
      such cycles are found they may give important information about Precambrian
      tectonism and glaciation.

PMID- 29451242
TI  - High-sensitivity detection of negative ions in the stratosphere.
AB  - Mass spectrometer composition measurements of stratospheric negative ions were
      first made by Arnold and Henschen1 using a balloon-borne instrument. These
      initial measurements, which were taken at an altitude of 36.5 km, revealed that
      the major ion species are NO-3(HNO3)a and HSO-4(H2SO4)b(HNO3)c. The suggestion
      that the unexpected HSO-4 cores are formed from NO-3 cores by a reaction
      involving stratospheric sulphuric acid vapour1 was strongly supported by
      laboratory measurements of the relevant ion-molecule reactions by Viggiano and
      colleagues2. Meanwhile, major instrumental refinements in balloon-borne ion mass
      spectrometers, including increased mass range, sensitivity and mass resolution,
      have resulted in the detection of more massive HSO-4(H2SO4)b ions and in the
      extension of the height range from a thin layer around 35 km to a region
      extending from 23 to 39 km (refs 3,4). Here we report in situ negative ion
      composition measurements of even higher sensitivity which led to the detection of
      previously unobserved ion species.

PMID- 29451243
TI  - Wild-type tRNATyrG reads the TMV RNA stop codon, but Q base-modified tRNATyrQ
      does not.
AB  - Although protein synthesis usually terminates when a stop codon is reached along
      the messenger RNA sequence, there are examples, mainly in viruses, of the stop
      codon being suppressed by a tRNA species. A strong candidate for this phenomenon
      occurs in tobacco mosaic virus (TMV) in the form of two proteins (110K and 160K,
      of molecular weights 110,000 and 160,000, respectively)1, sharing an N-terminus
      sequence, which are translated in vitro from a purified species of viral RNA. We
      have investigated the identity of the tRNA responsible for production of the 160K
      protein and show here that it is one of the tyrosine tRNAs. Another tyrosine
      tRNA, in which the first base of the anticodon is highly modified, does not act
      as a suppressor, indicating the possible regulatory function of such
      modifications.

PMID- 29451244
TI  - Near-edge X-ray absorption spectra for metallic Cu and Mn.
AB  - The measurement of X-ray absorption fine structure of metals- both in the
      extended region (EXAFS) as well as in the near edge region (XANES)-has been
      widely discussed (see refs 1-6 for Cu and refs 7-9 for Mn). The recent
      availability of intense X-ray fluxes from storage rings has usually been
      exploited for EXAFS leaving the XANES often with poorer resolution than earlier
      work performed on conventional sources (for example, compare the near edge
      structure for copper in ref. 1 with refs 3 or 6). In addition, whilst the theory
      and analysis of EXAFS is relatively well-established2,10, a theory for the strong
      scattering regime near to the absorption edge has only recently been developed11.
      We report here the first high resolution XANES spectra for Cu and Mn which were
      performed at the SRS storage ring at Daresbury. Although both metals have close
      packed structures consisting of atoms of similar size their local atomic
      structure is different in detail. Significant differences are found in their
      respective XANES reflecting the senstivity of this region of the X-ray absorption
      fine structure to the local atomic structure. Spectra for the two metals have
      been analysed using the new multiple scattering formalism. This is a real space
      calculation and unlike a conventional band structure approach it does not require
      structural periodicity but works from the local arrangement of atoms.

PMID- 29451245
TI  - UK Government Chemist: New broom.

PMID- 29451246
TI  - Belgium's power.

PMID- 29451247
TI  - Page charges.

PMID- 29451248
TI  - Good as gold.

PMID- 29451249
TI  - Eureka! No mystique to creative thinking.

PMID- 29451251
TI  - German energy policy: The future unclear.

PMID- 29451250
TI  - 99 Years ago.

PMID- 29451252
TI  - Polish science: Academy for change.

PMID- 29451253
TI  - Closure threat at FDA laboratories.

PMID- 29451254
TI  - Depth in stability for the cognoscenti.

PMID- 29451255
TI  - Harsh words.

PMID- 29451256
TI  - Crucial colonization.

PMID- 29451257
TI  - A spectrum of achievements.

PMID- 29451259
TI  - Nuclear Structure Facility: Nylon slip shows.

PMID- 29451258
TI  - High energy physics grows tenfold.

PMID- 29451260
TI  - Strontium isotopic resolution of magma dynamics in a layered intrusion.
AB  - Kalka is one of about 14 major layered mafic-ultramafic intrusions forming the
      Giles Complex in central Australia1. The stratigraphical section of the Kalka
      Intrusion passes from a basal pyroxenite zone (450 + m) through norite and
      olivine gabbro zones (3,500 m) to an uppermost anorthosite zone (800 + m)2.
      Further resolution into 21 cyclic units is derived from repeated mineral
      crystallization sequences and cyclical variation in plagioclase and olivine
      compositions. A conventional interpretation would have a basaltic magma
      progressively fractionating as crystallization proceeded from mafic base to
      leucocratic top, with periodic resetting to less evolved states by fresh
      incursions of primary magma or by convectional overturn within a sealed magma
      chamber. However, the reconnaissance isotopic data reported here indicate
      development of a more complex open system. High initial 87Sr/86Sr ratios in
      conjunction with normal 143Nd/144Nd ratios demonstrate massive contamination by
      country rock within the main part of the intrusion3. Furthermore, great variation
      in Sr initial ratios from 0.7049 to 0.7088 suggests substantial changes in magma
      composition beyond those induced by fractionation. Similar isotopic heterogeneity
      in the Newer Gabbros of Scotland4 and the Bushveld Complex5 has been attributed
      to variable contamination or the emplacement of magma batches of differing
      composition.

PMID- 29451262
TI  - Californian Medflies: Brief armistice.

PMID- 29451261
TI  - Solid-state reduction of iron in olivine-planetary and meteoritic evolution.
AB  - Iron-nickel metallic particles have been reported in meteorites1 and lunar2-5 and
      terrestrial6,7 rocks. The origin of these metallic particles is not unique as
      they may be formed by (1) condensation from a primordial solar nebula8; (2)
      crystallization from a melt; and (3) subsolidus reduction reactions under low
      oxygen or sulphur fugacity. We report here an electron microscopy study of the
      solid-state microstructural development in olivine single crystals (Fo92) in
      which half of the iron has been reduced to the metallic state by a gas-solid
      interaction in the temperature range 950-1,500  degrees C. The reaction, Fo92
      >Fo96+metallic Fe(Ni in solid solution)+pyroxene, begins with a homogeneous
      transformation involving fine-scale metallic precipitates resembling Guinier
      Preston zones9. The microstructure develops by the growth of the first-formed
      precipitates during an Ostwald ripening process9 in which the precipitates
      located in the dislocation sub-boundaries develop in preference to precipitates
      in the subgrains. On the other hand, pyroxene is first observed to nucleate
      heterogeneously at pre-existing dislocations and its coarsening rate is more than
      an order-of-magnitude faster than that of the metallic phase. Besides the
      textural similarity of the observed microstructures with that reported for some
      of the lunar materials2, these results have important implications for the
      physical models of accretion of terrestrial planets, planetesimals and
      meteorites10, especially with respect to the distribution of siderophile
      elements. The rate of reaction observed here places constraints on models for the
      formation of the Earth's core by segregation of a metallic phase with or without
      reduction.

PMID- 29451263
TI  - Science research council: Paying a price.

PMID- 29451264
TI  - Asian mycotoxins.

PMID- 29451265
TI  - Albanian development: Hoxha looks ahead.

PMID- 29451266
TI  - Early archaeological sites, hominid remains and traces of fire from Chesowanja,
      Kenya.
AB  - Recent investigations of Lower Pleistocene sites at Chesowanja have yielded in
      situ Oldowan and Oldowan-like stone artefacts, evidence of fire and a fragmentary
      'robust' australopithecine cranium. Burnt clay found at one artefact locality
      dated to >1.42+/-0.07 Myr is the earliest known evidence of fire associated with
      a hominid occupation site.

PMID- 29451267
TI  - Structural features in ethanol-water mixtures revealed by picosecond fluorescence
      anisotropy.
AB  - When an ensemble of molecules is excited with polarized light an anisotropic
      orientational distribution with respect to the transition dipole moment is
      produced. This anisotropy can decay in time due to the rotational motion of the
      molecules and consequently leads to depolarization of the fluorescence1-6. The
      rate of this rotational motion has been successfully predicted from hydrodynamic
      theory. How much the rotational relaxation depends on molecular geometry and how
      much on specific solvent-solute interactions has been studied by picosecond
      spectroscopy1-6 and other techniques7-9. In all cases so far reported, the
      rotational behaviour seems to be accounted for by the Debye-Stokes-Einstein (DSE)
      equation tauR = f/kT. This relates the rotational relaxation time tauR (inversely
      related to the rotational diffusion coefficient) to the frictional coefficient,
      f, which is proportional to the product of the shear viscosity, the molecular
      volume and a constant dependent on the 'stick' or 'slip' boundary
      conditions3,10,11. We report here, however, that large deviations from DSE
      behaviour have been observed in the rotational diffusion of the dye cresyl violet
      in ethanol-water mixtures. Different rotational relaxation times are observed in
      solutions of the same viscosity but differing composition. This behaviour can be
      rationalized using previously proposed models for water-ethanol mixtures.

PMID- 29451268
TI  - How cells live together.

PMID- 29451269
TI  - Subduction of the Cocos plate in the Mid America Trench.
AB  - The Mid America Trench, off the Pacific coast of southern Mexico and central
      America, is the site of northeastward subduction of the Cocos oceanic plate under
      the North America and Caribbean plates1 (Fig. 1). In Guatemala, the North America
      and Caribbean plates are separated by the Polochic-Motagua left-lateral strike
      slip faults (Fig. 1). The trench itself appears to be divided into two distinct
      sections at its intersection with the Tehuantepec Ridge. To the south the margin
      of the trench is wide and consists of a well developed shelf basin2 bounded on
      the east by a huge volcanic cordillera parallel with the trench axis at a
      distance of ~200 km. In contrast, to the north, the margin is narrow and devoid
      of shelf basin; landwards, the trans-Mexican volcanic belt trends oblique to the
      trench. This volcanic chain would be anomalous if it were related to the
      subduction of the Cocos plate off southern Mexico. In 1979, as part of the
      International Phase of Ocean Drilling (IPOD) of the Deep Sea Drilling Project,
      Legs 66 and 67 respectively explored the northern (off Acapulco, Mexico) and
      southern (off San Jose, Guatemala) section of the Mid America Trench3-6 (Fig. 1).
      Since then short topographical surveys of the trench have been carried out by RV
      Jean Charcot8 using the sea-beam technique7. We report here that both sets of
      data, together with UTMSI multichannel seismic profiles10,11 can be used to
      reconstruct the processes of subduction along the Mid America Trench.

PMID- 29451270
TI  - Tripping the light fantastic.

PMID- 29451271
TI  - Caltech: Kellogg birthday.

PMID- 29451274
TI  - Helicase-primase inhibitor amenamevir for herpesvirus infection: Towards
      practical application for treating herpes zoster.
AB  - Valacyclovir and famciclovir enabled successful systemic therapy for treating
      herpes simplex virus (HSV) and varicella zoster virus (VZV) infection by their
      phosphorylation with viral thymidine kinase. Helicase-primase inhibitors (HPIs)
      inhibit the progression of the replication fork, an initial step in DNA synthesis
      to separate the double strand into two single strands. The HPIs amenamevir and
      pritelivir have a novel mechanism of action, once-daily administration with
      nonrenal excretory characteristics, and clinical efficacy for genital herpes.
      Amenamevir exhibits anti-VZV and anti-HSV activity while pritelivir only has anti
      HSV activity. A clinical trial of amenamevir for herpes zoster has been
      completed, and amenamevir has been licensed and successfully used in 20,000
      patients with herpes zoster so far in Japan. We have characterized the features
      of the antiviral action of amenamevir and, unlike acyclovir, the drug's antiviral
      activity is not influenced by the viral replication cycle. Amenamevir is opening
      a new era of antiherpes therapy.

PMID- 29451272
TI  - The NDPK/NME superfamily: state of the art.
AB  - Nucleoside diphosphate kinases (NDPK) are nucleotide metabolism enzymes encoded
      by NME genes (also called NM23). Given the fact that not all NME-encoded proteins
      are catalytically active NDPKs and that NM23 generally refers to clinical studies
      on metastasis, we use here NME/NDPK to denote the proteins. Since their discovery
      in the 1950's, NMEs/NDPKs have been shown to be involved in multiple
      physiological and pathological cellular processes, but the molecular mechanisms
      have not been fully determined. Recent progress in elucidating these underlying
      mechanisms has been presented by experts in the field at the 10th International
      Congress on the NDPK/NME/AWD protein family in October 2016 in Dubrovnik,
      Croatia, and is summarized in review articles or original research in this and an
      upcoming issue of Laboratory Investigation. Within this editorial, we discuss
      three major cellular processes that involve members of the multi-functional
      NME/NDPK family: (i) cancer and metastasis dissemination, (ii) membrane
      remodeling and nucleotide channeling, and iii) protein histidine phosphorylation.

PMID- 29451275
TI  - Cenegermin for the treatment of neurotrophic keratitis.
AB  - The trigeminal nerve provides corneal sensitivity and trophic supply to corneal
      tissues. The impairment of corneal innervation leads to development of
      neurotrophic keratitis (NK). NK is a rare, degenerative corneal disease
      characterized by corneal hypo/anesthesia and development of nonhealing corneal
      epithelial defects and ulcers. NK is a challenging condition with high medical
      need due to the lack of approved treatments that can restore corneal integrity.
      Current treatment of NK aims at stimulating corneal healing and preventing
      disease progression. Cenegermin is a recombinant human nerve growth factor that
      was safe and well tolerated in preclinical and clinical studies. Cenegermin eye
      drops were safe and effective in restoring corneal integrity in two phase II
      clinical trials in patients with NK. The European Commission granted a full
      marketing authorization to cenegermin eye drops for the treatment of moderate to
      severe NK in July 2017.

PMID- 29451276
TI  - Tisagenlecleucel, an approved anti-CD19 chimeric antigen receptor T-cell therapy
      for the treatment of leukemia.
AB  - On August 30, 2017, the U.S. Food and Drug Administration (FDA) approved
      Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune
      product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment
      of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). This was a
      milestone in tumor immunology on account of the significant antitumor effect of
      tisagenlecleucel for the treatment of relapsed/refractory B-ALL patients.
      Conventional standard therapies for B-ALL have high failure rates, thus
      developing new therapies is crucial for patients with B-ALL. Results from
      clinical trials indicate that anti-CD19 CAR T-cell therapies could successfully
      induce high response rates in B-ALL patients. However, related toxicities, such
      as cytokine release syndrome and CAR T-cell-related encephalopathy syndrome, may
      be severe or even fatal, and the management of such toxicities is therefore
      vital. This review will focus on the clinical application of anti-CD19 CAR T-cell
      therapy in B-ALL treatment, including design features of CAR constructs,
      therapeutic use of tisagenlecleucel, CAR T-cell therapy clinical trials and
      related toxicity, and prospects for cancer immunotherapy.

PMID- 29451277
TI  - Tivozanib: a new treatment option for renal cell carcinoma.
AB  - Tivozanib is a tyrosine kinase inhibitor that targets all vascular endothelial
      growth factor receptors (VEGFRs), causing inhibition of angiogenesis. It has
      recently been approved by the European Medicines Agency (EMA) for first-line
      treatment of adult patients with advanced renal cell carcinoma (RCC) and for
      adult patients who are VEGFR and mammalian target of rapamycin (mTOR) pathway
      inhibitor-naive, following disease progression after one prior treatment with
      cytokine therapy for advanced RCC. This review will focus on mechanisms of
      action, early drug development and results of published and ongoing clinical
      trials of tivozanib.

PMID- 29451278
TI  - United European Gastroenterology Week (UEGW) 2017 - 25th Annual Conference
      (October 28-November 1, 2017 - Barcelona, Spain).
AB  - The 25th United European Gastroenterology Week (UEGW), the largest European
      conference centered on diseases of the stomach, bowel, esophagus, liver, pancreas
      and gallbladder, was held in Barcelona, Spain. This 5-day meeting attracted over
      13,000 delegates to share recent research in the treatment of gastrointestinal
      and liver diseases. The conference provided teaching material, workshops and live
      sessions to all the attendants. The reports will cover the latest research into
      treatments for these diseases.

PMID- 29451279
TI  - Nitrogen doped nanohoops as promising CO2 capturing devices.
AB  - The impact of climate change in the face of steady or increasing emissions has
      made the capture and storage of CO2 a priority issue. Supramolecular chemistry is
      one of the tools that can be used for this task, due to the possibility of tuning
      intermolecular interactions for the capture of this gas in a selective and
      efficient way. In this context, this work presents a novel approach for the
      capture of CO2 based on n-cycloparaphenylenes ([n]-CPPs) doped with nitrogen
      atoms. This is the first time that the potential of these structures for the
      capture of polluting gases has been evaluated. Among all the structures analysed,
      the one yielding the best results (complexation energy of -32.80 kJ mol-1)
      contains 4 nitrogen atoms per monomer. The topology of the electron density of
      the host-guest complex and the nature of its non-covalent interactions have been
      analyzed in this work in order to explain this high binding energy and identify
      potential structural modifications to improve it. The capability of this system
      to be used as a sensing device for CO2 using vibrational spectroscopy is also
      explored.

PMID- 29451280
TI  - A remote computing based point-of-care colorimetric detection system with a
      smartphone under complex ambient light conditions.
AB  - Smartphone-based colorimetric detection has been one of the most commonly used
      techniques for point-of-care detection in recent years. However, there are two
      defects in the current detection system. One is the need of a light-tight box to
      isolate the impact of ambient light, and the other is the increased calculation
      with the number of probes. In this paper, a colorimetric detection system was
      coupled with a new color calibration method for detection under complex ambient
      light conditions. A 3 * 4 colorimetric probe array was used to display the color
      changes of different analytes. With the color calibration function and the
      Support Vector Machine discrimination function based on the RGB data captured at
      5000 K preloaded in a remote server, the analysis results could be fed back
      immediately after sending the RGB data captured under complex ambient light
      conditions by the smartphone to the remote server. The discrimination results
      showed that this colorimetric detection system has a relatively high accuracy
      under complex ambient light conditions. An optimal probe selection algorithm
      (OPSA) based on the improvement of the traditional stepwise discriminant analysis
      was also proposed to dramatically reduce the number of probes for the
      identification of various analytes. The analysis results showed that this
      algorithm significantly simplifies the probe array and the simplified probe array
      kept exhibiting a good classification performance. Our research eliminates the
      dependence of smartphone-based colorimetric detection on light-tight boxes and
      cuts off the redundant probes, thereby greatly improving the portability of
      smartphone-based colorimetric detection.

PMID- 29451281
TI  - Fluorescent antitumor titanium(iv) salen complexes for cell imaging.
AB  - Two differently substituted fluorescent salen Ti(iv) complexes were developed.
      One was inactive on human cancer cells, whereas the other showed high
      cytotoxicity. Based on live cell imaging, both complexes penetrated the cell, but
      were not detected in the nuclei. Moreover, the inactive complex was trapped in
      endocytic vesicles, whereas the active complex accumulated in the perinuclear
      region and inflected phototoxicity upon continuous irradiation.

PMID- 29451282
TI  - Catalyst surfaces with tunable hydrophilicity and hydrophobicity: metal-organic
      frameworks toward controllable catalytic selectivity.
AB  - This report describes a facile strategy that has the capability of adjusting
      different surface hydrophilicities/hydrophobicities of catalysts by covering
      metal-organic frameworks with graphene oxide and reduced graphene oxide. The
      catalysts exhibit remarkable catalytic selective performance for the
      hydrogenation of different hydrophobic and hydrophilic reactants.

PMID- 29451283
TI  - A chemo- and regiocontrolled approach to bipyrazoles and pyridones via the
      reaction of ethyl 5-acyl-4-pyrone-2-carboxylates with hydrazines.
AB  - Chemo- and regiocontrolled syntheses of pyrazoles and pyridones are presented on
      the basis of 4-pyrones. A novel approach towards highly functionalized 3,4'
      bipyrazoles has been developed by using reactions of ethyl 5-acylcomanoates with
      hydrazines. The acid-promoted double cyclocondensation allows switching of the
      structure of the pyrazole rings easily through changing both the nature of
      hydrazine and the reaction conditions. The transformation of 4-pyrones with
      phenylhydrazine in EtOH at -20  degrees C leads to hydroxypyridones as
      monoaddition products which can be used as precursors for the preparation of
      pyridone and pyrazole derivatives. A novel rearrangement of 2-hydroxypyridone to
      pyrazolyl-1,3-diketones in DMSO was found. The structure and regiochemistry of
      bipyrazoles were confirmed by X-ray analysis and 2D NMR experiments.

PMID- 29451284
TI  - Effect of the coverage level of carboxylic acids as a modifier for barium
      titanate nanoparticles on the performance of poly(vinylidene fluoride)-based
      nanocomposites for energy storage applications.
AB  - Surface modification on nanoparticle fillers with organic groups is important to
      improve the performance of ceramic/polymer nanocomposites. Due to the small
      coverage level of carboxylic acids on the nanoparticle surface, studies on the
      use of carboxylic acids as a surface modifier for ceramic nanoparticles have been
      rarely reported. However, there is no study that proves that a small amount of
      modifier on the surface of nanoparticles cannot adequately improve the dispersion
      as well as the compatibility of nanoparticles with the matrix. Herein, we used
      three carboxylic acids to treat the surface of BaTiO3 (BT) nanoparticles and
      adjusted the coverage level of the modifiers on the surface of BT nanoparticles
      through different ways. The nanocomposite films synthesized from the modified BT
      nanoparticles dispersed in the poly(vinylidene fluoride) (PVDF) polymer matrix
      were analyzed by dielectric spectroscopy, breakdown strength, leakage currents,
      and D-E loop measurements. The results show that the molecule dipole moment and
      polarizability of the modifier greatly influence the permittivity of the
      nanocomposites as the surface coverage level of the modifiers increases. Due to
      many influential factors, changes in the breakdown strength of the nanocomposites
      show diversity for three modifiers as the modifier content increases. For the
      nanocomposites applied in energy storage, the optimal content of the modifier on
      the surface of the nanoparticles needs to be determined by combining various
      properties of the nanocomposites.

PMID- 29451285
TI  - Modeling solvent evaporation during thin film formation in phase separating
      polymer mixtures.
AB  - Preparation of thin films by dissolving polymers in a common solvent followed by
      evaporation of the solvent has become a routine processing procedure. However,
      modeling of thin film formation in an evaporating solvent has been challenging
      due to a need to simulate processes at multiple length and time scales. In this
      work, we present a methodology based on the principles of linear non-equilibrium
      thermodynamics, which allows systematic study of various effects such as the
      changes in the solvent properties due to phase transformation from liquid to
      vapor and polymer thermodynamics resulting from such solvent transformations. The
      methodology allows for the derivation of evaporative flux and boundary conditions
      near each surface for simulations of systems close to the equilibrium. We apply
      it to study thin film microstructural evolution in phase segregating polymer
      blends dissolved in a common volatile solvent and deposited on a planar
      substrate. Effects of the evaporation rates, interactions of the polymers with
      the underlying substrate and concentration dependent mobilities on the kinetics
      of thin film formation are studied.

PMID- 29451286
TI  - Addressing the temperature transferability of structure based coarse graining
      models.
AB  - Systematically derived coarse grained (CG) models for molecular liquids do not
      inherently guarantee transferability to a state point different from its
      reference, especially when derived on the basis of structure based CG methods
      like Inverse Monte Carlo (IMC). Several efforts made in the past years to improve
      the transferability of these models focused on including thermodynamic
      constraints or on the application of multistate parametrization. Das and Andersen
      (DA) [Das et al., J. Chem. Phys., 2010, 132, 164106.] proposed a different
      Ansatz. They derived a correction term added to the system's Hamiltonian to
      reproduce the virial pressure and the volume fluctuations of the reference system
      in the CG resolution which does not require further adjustment of the effective
      pair potential. Herein, we discuss the possibility to achieve temperature
      transferability with IMC models for selected alkanes following the optimization
      of the DA approach as proposed by Dunn and Noid (DN) [Dunn et al., J. Chem.
      Phys., 2015, 143, 243148.]. The work focuses on a novel approach to determine the
      DN correction term for different state points by linear interpolation.

PMID- 29451288
TI  - Fibers on the surface of thermo-responsive gels induce 3D shape changes.
AB  - Using computational modeling, we pattern the outer layers of thin, thermo
      responsive gels with elastic fibers and thereby design stable structures that
      could not be achieved with the fibers in the interior of the network. To perform
      these studies, we simulate the fiber-decorated gels with the gel lattice spring
      model (gLSM) and determine how the temperature, arrangement and number of the
      fibers control the bending and curvature of the thin films. We establish
      arrangements of the fiber on square- and rectangular-shaped gels that yield
      reversible, pronounced contraction and extension of the layer with changes in
      temperature. Hence, these composites provide useful actuation. Finally, we cut
      the gel into a cross-shaped sample to show that the modes of actuation and
      functionality of the material can be significantly expanded by tailoring not only
      the fiber placement, but also the initial geometry of the gel.

PMID- 29451287
TI  - Computational identification of the binding mechanism of a triple reuptake
      inhibitor amitifadine for the treatment of major depressive disorder.
AB  - Amitifadine, the only drug ever clinically tested in Phase 3 for treating
      depression, is a triple reuptake inhibitor (TRI) that simultaneously interacts
      with human monoamine transporters (MATs) including hSERT, hNET and hDAT. This
      novel multi-target strategy improves drug efficacy and reduces the toxic side
      effects of drugs. However, the binding modes accounting for amitifadine's
      polypharmacological mode of action are still elusive, and extensive exploration
      of the amitifadine-target interactions between amitifadine and MATs is urgently
      needed. In this study, a total of 0.63 MUs molecular dynamics (MD) simulations
      with an explicit solvent as well as endpoint binding free energy (BFE)
      calculation were carried out. MD simulation results identified a shared binding
      mode involving eleven key residues at the S1 site of MATs for the binding of
      amitifadine, and the results of the BFE calculations were in good agreement with
      experimental reports. Moreover, by analyzing the per-residue energy contribution
      variation at the S1 site of three MATs and additional cross-mutagenesis
      simulations, the variation in the inhibition ratio of amitifadine between hSERT
      and two other MATs was discovered to mainly come from non-conserved residues
      (Y95, I172 and T439 in hNET and Y95, I172, A169 and T439 in hDAT). As the
      rational inhibition ratio of multi-target drugs among various therapeutic targets
      was found to be the key to their safety and tolerance, the findings of this study
      may further facilitate the rational design of more potent but less toxic multi
      target antidepressant drugs.

PMID- 29451289
TI  - Multi-molecular emission of a cationic Pt(ii) complex through hydrogen bonding
      interactions.
AB  - The cationic Pt complexes with amide groups have been found to show dimer
      emission through hydrogen bonding interactions with counter anions even at low
      concentration. In order to investigate further details of dimer emission, we
      prepared three Pt complexes, Pt.B(C6F5)4, Pt.Cl, and Pt.PF6, whose counter anions
      possess different strengths of a hydrogen bonding acceptor. Hydrogen bonding
      interactions in the ground state and excited-state dynamics of the Pt complexes
      were evaluated by NMR analysis, temperature dependence, and kinetics of dimer
      emission. These studies revealed that the hydrogen bonding interaction in the
      ground state is essential for dimer emission, but too strong hydrogen bonding
      prevents dimer emission due to the inhibition of a stacked dimer formation in the
      excited state. Owing to this trade-off, the Pt complex with a moderate hydrogen
      bonding acceptor, PF6-, most effectively shows dimer emission. In general, a
      strong supramolecular interaction efficiently provides a desired assembled
      structure showing multi-molecular emission. We revealed a unique phenomenon that
      a moderate interaction is beneficial to effective multi-molecular emission.

PMID- 29451290
TI  - High temperature pyrolysis of 2-methyl furan.
AB  - The dissociation of 2-methyl furan at high temperatures has been studied in a
      combined experimental and theoretical approach to elucidate the details of this
      multi-channel unimolecular reaction. Laser schlieren densitometry studies were
      performed in a diaphragmless shock tube over the range 1600 < T < 2300 K and
      three pressures 60, 120 and 240 Torr. The theoretical study identified many
      reaction paths, most of which are initiated by the formation of carbenes. Of
      these paths, five account for 99% consumption of 2MF, and three account for 95%
      consumption. Simulations of the experimental results with a model that
      incorporated the theoretical predictions of reaction paths failed to reproduce
      the experimental data. This was resolved by increasing the rate of loss of an H
      atom from the methyl group in 2-methyl furan by a factor of 2-4. The resulting
      model provides good simulations of the complete set of experimental data. The
      branching fractions for the three key reactions are both temperature and pressure
      dependent.

PMID- 29451291
TI  - Enhanced glucose sensing based on a novel composite CoII-MOF/Acb modified
      electrode.
AB  - In this work, we demonstrate the synthesis and application of a novel CoII-based
      metal-organic framework {[Co2(Dcpp)(Bpe)0.5 (H2O)(MU2-H2O)].(Bpe)0.5}n (CoII-MOF,
      H4Dcpp = 4,5-bis(4'-carboxylphenyl)-phthalic acid, Bpe = 1,2-bis(4
      pyridyl)ethane) as an electrochemical sensor for glucose detection. Single
      crystal X-ray diffraction analysis shows that the CoII-MOF has a two-dimensional
      (2D) bilayer structure composed of Co2 units and Dcpp4- ligands. There are two
      kinds of Bpe in the structure: one serves as a bidentate ligand linking two Co1
      atoms in each 2D layer; the other is just free in the lattice. The CoII-MOF
      modified glassy carbon electrode (GCE) shows good electrocatalytic activity
      towards glucose oxidation. To further improve the catalytic activity of the
      electrode, a new composite of CoII-MOF/acetylene black (CoII-MOF/Acb) was
      constructed. The CoII-MOF/Acb modified electrode exhibits enhanced sensing
      behavior for glucose detection. The sensing performance of CoII-MOF/Acb/GCE with
      different Acb loadings was investigated in detail. The results demonstrate that
      CoII-MOF/GCE with 2% Acb (CoII-MOF/Acb-2%/GCE) exhibits the best sensing
      behavior, including a high sensitivity of 0.255 MUA MUM-1 cm-2 and a wide linear
      range of 5-1000 MUM, as well as a low detection limit of 1.7 MUM (S/N = 3). It's
      worth noting that the linear range of CoII-MOF/Acb-2%/GCE was extended by more
      than ten times when compared to that of CoII-MOF/GCE without Acb addition. In
      addition, CoII-MOF/Acb-2%/GCE shows good selectivity and stability in the sensing
      process.

PMID- 29451292
TI  - Multifunctional luminescent magnetic cryocooler in a Gd5Mn2 pyramidal complex.
AB  - Magnetic cooling is a highly efficient refrigeration technique with the potential
      of replacing expensive and rare helium-3 in the field of ultra-low temperature
      cooling. However, the visualization of a cryogen at an extremely low temperature
      and in a strong magnetic field is challenging, but it is crucial for the precise
      positioning and in situ thermal probe measurements in potential practical
      applications. Here, the activation of a red-emissive Mn(ii) ion using 3d/4f
      chemistry produces a luminescent molecule cooler,
      [Gd5Mn2(LOMe)2(OH)4(Ac)6(MeOH)10Cl2]Cl3.2MeOH (1), with the core of an Mn(ii)
      anchored heptanuclear [GdIII5MnII2] pyramid. The photoluminescence (PL) of the
      Mn2+ emission, with a large Stokes shift (lambdaem ~ 690 nm) from 4T1(4G) ->
      6A1(6S), shows not only a sensitive temperature sensing property but also
      reversible mechanoluminescence (ML). More attractively, these findings reveal a
      considerable magnetocaloric effect (MCE) coupled with a tunable emission window,
      opening up new opportunities in the multifunctional applications of PL, ML, and
      the MCE involving red-light sources, thermometers, and stress imaging. In
      particular, this provides a novel resolution to design visualized PL coolers.

PMID- 29451293
TI  - The role of near-wall drag effects in the dynamics of tethered DNA under shear
      flow.
AB  - We utilized single-molecule tethered particle motion (TPM) tracking, optimized
      for studying the behavior of short (0.922 MUm) dsDNA molecules under shear flow
      conditions, in the proximity of a wall (surface). These experiments track the
      individual trajectories through a gold nanobead (40 nm in radius), attached to
      the loose end of the DNA molecules. Under such circumstances, local interactions
      with the wall become more pronounced, manifested through hydrodynamic
      interactions. To elucidate the mechanical mechanism that affects the statistics
      of the molecular trajectories of the tethered molecules, we estimate the resting
      diffusion coefficient of our system. Using this value and our measured data, we
      calculate the orthogonal distance of the extended DNA molecules from the surface.
      This calculation considers the hydrodynamic drag effect that emerges from the
      proximity of the molecule to the surface, using the Faxen correction factors. Our
      finding enables the construction of a scenario according to which the tension
      along the chain builds up with the applied shear force, driving the loose end of
      the DNA molecule away from the wall. With the extension from the wall, the
      characteristic times of the system decrease by three orders of magnitude, while
      the drag coefficients decay to a plateau value that indicates that the molecule
      still experiences hydrodynamic effects due to its proximity to the wall.

PMID- 29451294
TI  - Quantification of isomerically summed hydrocarbon contributions to crude oil by
      carbon number, double bond equivalent, and aromaticity using gas chromatography
      with tunable vacuum ultraviolet ionization.
AB  - The ability to structurally characterize and isomerically quantify crude oil
      hydrocarbons relevant to refined fuels such as motor oil, diesel, and gasoline
      represents an extreme challenge for chromatographic and mass spectrometric
      techniques. This work incorporates two-dimensional gas chromatography coupled to
      a tunable vacuum ultraviolet soft photoionization source, the Chemical Dynamics
      Beamline 9.0.2 of the Advanced Light Source at the Lawrence Berkeley National
      Laboratory, with a time-of-flight mass spectrometer (GC * GC-VUV-TOF) to directly
      characterize and isomerically sum the contributions of aromatic and aliphatic
      species to hydrocarbon classes of four crude oils. When the VUV beam is tuned to
      10.5 +/- 0.2 eV, both aromatic and aliphatic crude oil hydrocarbons are ionized
      to reveal the complete chemical abundance of C9-C30 hydrocarbons. When the VUV
      beam is tuned to 9.0 +/- 0.2 eV only aromatic hydrocarbons are ionized, allowing
      separation of the aliphatic and aromatic fractions of the crude oil hydrocarbon
      chemical classes in an efficient manner while maintaining isomeric
      quantification. This technique provides an effective tool to determine the
      isomerically summed aromatic and aliphatic hydrocarbon compositions of crude oil,
      providing information that goes beyond typical GC * GC separations of the most
      dominant hydrocarbon isomers.

PMID- 29451295
TI  - Evaluation of HIF-1alpha and iNOS in ischemia/reperfusion gastric model:
      bioimpedance, histological and immunohistochemical analyses.
AB  - : Gastrointestinal ischemia/reperfusion (I/R) generates pathological alterations
      that could lead to death. Early ischemic damage markers could be used to guide
      therapy and improve outcomes. AIM: To relate hypoxia-inducible factor 1alpha (HIF
      1alpha) activation and inducible nitric oxide synthase (iNOS) expression to
      gastric impedance changes due to I/R damage. METHODS: Experimental animals were
      randomly distributed into 3 groups: control, ischemia (30 min) and I/R (60 min).
      Gastric ischemia was generated by celiac artery clamping for 30 min, and then
      blood flow was restored for 60 min. Impedance spectra and biopsies of the
      glandular portion were obtained for histological and immunohistochemical
      analyses. Immunodetection of both HIF-1alpha and iNOS was performed. RESULTS:
      Under ischemia and I/R conditions, there was an increase (p<0.05) in the
      impedance parameters. Histologically, under ischemic conditions, edema and
      necrosis were observed in epithelium and significant vascular congestion. In I/R
      condition, alterations of the glandular and luminal integrity were found, which
      generated areas of epithelial erosion. Immunohistochemical analysis of HIF-1alpha
      revealed an increase (p<0.01) in the number of immunoreactive cells in the
      ischemia (35.7+/-13.9) and I/R (119.9+/-18.8) conditions compared to the control
      (0.8+/-1.2). Immunodetection of iNOS showed an increase (p<0.01) in the number of
      cells expressing iNOS under the ischemia (5.4+/-2.9) and I/R conditions (27.4+/
      11.3) was observed compared to the control (0.4+/-0.8). CONCLUSION: Early changes
      in impedance in response to I/R is related to histopathological changes, the
      nuclear stabilization and translocation of HIF-1alpha as well as expression of
      iNOS.

PMID- 29451296
TI  - Investigation of the urinary metabolic variations and the application in bladder
      cancer biomarker discovery.
AB  - Urine metabolomics have been used to identify biomarkers for clinical diseases.
      However, inter-individual variations and effect factors need to be further
      evaluated. In our study, we explored the urine metabolome in a cohort of 203
      health adults, 6 patients with benign bladder lesions, and 53 patients with
      bladder cancer (BCa) using liquid chromatography coupled with high resolution
      mass spectrometry. Inter-individual analysis of both healthy controls and BCa
      patients showed that the urine metabolome was relatively stable. Further analysis
      indicated that sex and age affect inter-individual variations in urine
      metabolome. Metabolic pathways such as tryptophan metabolism, the citrate cycle,
      and pantothenate and CoA biosynthesis were found to be related to sex and age. To
      eliminate age and sex interference, additional BCa urine metabolomic biomarkers
      were explored using age and sex-matched urine samples (Test group: 44 health
      adults vs. 33 patients with BCa). Metabolic profiling of urine could
      significantly differentiate the cases with cancer from the controls and high
      grade from low-grade BCa. A metabolite panel consisting of trans-2
      dodecenoylcarnitine, serinyl-valine, feruloyl-2-hydroxyputrescine, and 3
      hydroxynonanoyl carnitine were discovered to have good predictive ability for BCa
      with an area under the curve (AUC) of 0.956 (cross validation: AUC = 0.924). A
      panel of indolylacryloylglycine, N2 -galacturonyl-L-lysine, and aspartyl
      glutamate was used to establish a robust model for high- and low-grade BCa
      distinction with AUC of 0.937 (cross validation: AUC = 0.891). External sample
      (26 control vs. 20 BCa) validation verified the acceptable accuracy of these
      models for BCa detection. Our study showed that urinary metabolomics is a useful
      strategy for differential analysis and biomarker discovery.

PMID- 29451297
TI  - Enhancement of the conductivity detection signal in capillary electrophoresis
      systems using neutral cyclodextrins as sweeping agents.
AB  - Conductivity detection is a universal detection technique often encountered in
      electrophoretic separation systems, especially in modern chip-electrophoresis
      based devices. On the other hand, it is sparsely combined with another
      contemporary trend of enhancing limits of detection by means of various
      preconcentration strategies. This can be attributed to the fact that a
      preconcentration experimental setup usually brings about disturbances in a
      conductivity baseline. Sweeping with a neutral sweeping agent seems a good
      candidate for overcoming this problem. A neutral sweeping agent does not hinder
      the conductivity detection while a charged analyte may preconcentrate on its
      boundary due to a decrease in its effective mobility. This study investigates
      such sweeping systems theoretically, by means of computer simulations, and
      experimentally. A formula is provided for the reliable estimation of the
      preconcentration factor. Additionally, it is demonstrated that the conductivity
      signal can significantly benefit from slowing down the analyte and thus the
      overall signal enhancement can easily overweight amplification caused solely by
      the sweeping process. The overall enhancement factor can be deduced a priori from
      the linearized theory of electrophoresis implemented in the PeakMaster freeware.
      Sweeping by neutral cyclodextrin is demonstrated on an amplification of a
      conductivity signal of flurbiprofen in a real drug sample. Finally, a possible
      formation of unexpected system peaks in systems with a neutral sweeping agent is
      revealed by the computer simulation and confirmed experimentally.

PMID- 29451298
TI  - Micro-computed tomography visualization of the vestigial alimentary canal in
      adult oestrid flies.
AB  - Oestrid flies (Diptera: Oestridae) do not feed during the adult stage as they
      acquire all necessary nutrients during the parasitic larval stage. The adult
      mouthparts and digestive tract are therefore frequently vestigial; however,
      morphological data on the alimentary canal in adult oestrid flies are scarce and
      a proper visualization of this organ system within the adult body is lacking. The
      present work visualizes the morphology of the alimentary canal in adults of two
      oestrid species, Oestrus ovis L. and Hypoderma lineatum (de Villiers), with the
      use of non-invasive micro-computed tomography (micro-CT) and compares it with the
      highly developed alimentary canal of the blow fly Calliphora vicina Robineau
      Desvoidy (Diptera: Calliphoridae). Both O. ovis and H. lineatum adults showed
      significant reductions of the cardia and the diameter of the digestive tract, an
      absence of the helicoidal portion of the midgut typical of other cyclorrhaphous
      flies, and a lack of crop and salivary glands. Given the current interest in the
      alimentary canal in adult dipterans in biomedical and developmental biology
      studies, further understanding of the morphology and development of this organ
      system in adult oestrids may provide valuable new insights in several areas of
      research.

PMID- 29451299
TI  - Low childhood subjective social status and telomere length in adulthood: The role
      of attachment orientations.
AB  - Low subjective social status (SSS) in childhood places one at greater risk of a
      number of health problems in adulthood. Theoretical and empirical evidence
      indicates that exposure to supportive parenting may buffer the negative effects
      of low childhood SSS on adult health. Given the importance of supportive
      caregivers and close others for the development of attachment orientations
      throughout the lifespan, attachment theory may be important for understanding why
      some individuals are resilient to the negative effects of low childhood SSS on
      adult health while others are not. We examined if attachment anxiety and
      attachment avoidance altered the association between childhood subjective social
      status (SSS) and length of telomeres in white blood cells in adulthood. Shorter
      telomere length is associated with increased risk of age-related diseases
      including cancer, type 2 diabetes, and cardiovascular disease. Participants (N =
      128) completed self-report measures of childhood SSS and attachment orientations,
      as well as a blood draw. We found that among those with low childhood SSS, low
      attachment anxiety was associated with longer telomere length in white blood
      cells in comparison to high attachment anxiety controlling for participant age,
      sex, race, body mass index, and adult SSS. Among those with high childhood SSS,
      low attachment anxiety was associated with a slight decrease in telomere length.
      Attachment avoidance was unrelated to length of telomeres. Such findings provide
      further evidence for the role that close relationships may have on buffering SSS
      related health disparities.

PMID- 29451300
TI  - Decreased anterior cingulate activation in a motor task in youths with bipolar
      disorder.
AB  - BACKGROUND: Bipolar disorder (BP) is characterized by abnormal shifts in mood
      between episodes of mania and severe depression, both of which have been linked
      with psychomotor disturbances. This study compares brain activation patterns in
      motor networks between euthymic youths with BP and healthy controls (HC) during
      the completion of a simple motor task. METHODS: Thirty-five youths with BP and 35
      HC (aged 10-19) completed a self-paced sequential bilateral finger-tapping task,
      consisting of a 4-minute scan block with alternating 20-second periods of either
      the tapping task (six blocks) or rest (six blocks), while undergoing functional
      magnetic resonance imaging. Clinical and behavioral symptoms were assessed using
      the Child Behavior Checklist (CBCL). A between-group whole-brain analysis
      compared activation pattern differences while controlling for effects of age and
      sex. Clusters meeting whole-brain false discovery rate (FDR) correction (qFDR <
      .05) were considered statistically significant. Post hoc analyses evaluating
      comorbid attention-deficit/hyperactivity disorder (ADHD) in the BP group were
      also conducted. RESULTS: Significantly decreased activation was found in the
      anterior cingulate cortex (ACC) in youths with BP compared to HC. Furthermore,
      ACC activation was negatively correlated with CBCL mood dysregulation profile
      scores in the BP group. No significant differences in functional activation
      patterns were found between youths with BP and comorbid ADHD and those with only
      BP. CONCLUSIONS: These findings suggest a potential common mechanism of impaired
      ACC modulation between emotion dysregulation and motor processing in youths with
      BP.

PMID- 29451302
TI  - Comparing cytotoxic backbones for first-line trastuzumab-containing regimens in
      human epidermal growth factor receptor 2-positive advanced oesophagogastric
      cancer: A meta-analysis.
AB  - According to the Trastuzumab for Gastric Cancer (ToGA) study, trastuzumab plus
      cisplatin and capecitabine/5-fluorouracil (5-FU) is standard first-line treatment
      for human epidermal growth factor receptor 2 (HER2)-positive advanced
      oesophagogastric cancer. We examined the relative efficacy and safety of
      alternative trastuzumab-based cytotoxic backbone regimens compared to the
      standard ToGA regimen using meta-analysis. We searched Medline, EMBASE, CENTRAL
      and ASCO and ESMO up to March 2017 for studies investigating alternative first
      line trastuzumab-based regimens for HER2-positive oesophagogastric cancer,
      defined as high protein expression IHC3+ or IHC2+ and gene amplification by in
      situ hybridisation. We compared primary outcome overall survival (OS) of
      alternative trastuzumab-based regimens to the ToGA regimen. Hazard ratios (HRs)
      and 95% confidence intervals (95%CI) were calculated by extraction of the
      published Kaplan-Meier curves. Incidence counts and toxicity sample-sizes were
      extracted for adverse events and compared using single-arm proportion meta
      analysis in R. Fifteen studies (N = 557 patients) were included. OS was
      significantly longer with regimen trastuzumab plus doublet oxaliplatin and
      capecitabine/5-FU (median OS = 20.7 months) versus ToGA (16.0 months, HR = 0.75,
      95% CI = 0.59-0.99) and was less toxic. Trastuzumab plus doublet cisplatin and S
      1 showed no OS difference versus ToGA, but showed a different toxicity profile,
      including less hand-foot syndrome. Trastuzumab plus cisplatin or capecitabine as
      singlet backbone showed significantly worse survival and more toxicity versus
      ToGA regimen. Trastuzumab with triplet cytotoxic backbones or with bevacizumab
      and doublet cytotoxic backbone showed no survival benefit and more toxicity. In
      conclusion, trastuzumab plus doublet cytotoxic backbone containing oxaliplatin is
      preferable over the ToGA regimen with cisplatin. S-1 can substitute capecitabine
      or 5-FU when specific toxicities are encountered.

PMID- 29451301
TI  - INTU-related oral-facial-digital syndrome type VI: A confirmatory report.
AB  - Oral-facial-digital (OFD) syndromes are a subgroup of ciliopathies distinguished
      by the co-occurrence of hamartomas and/or multiple frenula of the oral region and
      digital anomalies. Several clinical forms of OFD syndromes are distinguished by
      their associated anomalies and/or inheritance patterns, and at least 20 genetic
      types of OFD syndromes have been delineated. We describe here a child with
      preaxial and postaxial polydactyly, lingual hamartoma, a congenital heart defect,
      delayed development and cerebellar peduncles displaying the molar tooth sign.
      Whole-exome sequencing and SNP array identified compound heterozygous variants in
      the INTU gene, which encodes a protein involved in the positioning of the ciliary
      basal body. INTU is a subunit of the CPLANE multiprotein complex essential for
      the assembly of IFT-A particles and intraflagellar transport. This report of a
      second patient with INTU-related OFD syndrome and the further delineation of its
      neuroimaging and skeletal phenotype now allow INTU-related OFD syndromes to be
      classified within the OFD syndrome type VI group. Patients display a phenotype
      similar to that of mice with a hypomorphic mutation of Intu, but with the
      addition of a heart defect.

PMID- 29451303
TI  - Sex-specific manifestation of genetic risk for attention deficit hyperactivity
      disorder in the general population.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is more commonly
      diagnosed in males than in females. A growing body of research suggests that
      females with ADHD might be underdiagnosed or receive alternative diagnoses, such
      as anxiety or depression. Other lines of reasoning suggest that females might be
      protected from developing ADHD, requiring a higher burden of genetic risk to
      manifest the disorder. METHODS: We tested these two hypotheses, using common
      variant genetic data from two population-based cohorts. First, we tested whether
      females and males diagnosed with anxiety or depression differ in terms of their
      genetic risk for ADHD, assessed as polygenic risk scores (PRS). Second, we tested
      whether females and males with ADHD differed in ADHD genetic risk burden. We used
      three different diagnostic definitions: registry-based clinical diagnoses,
      screening-based research diagnoses and algorithm-based research diagnoses, to
      investigate possible referral biases. RESULTS: In individuals with a registry
      based clinical diagnosis of anxiety or depression, females had higher ADHD PRS
      than males [OR(CI) = 1.39 (1.12-1.73)] but there was no sex difference for
      screening-based [OR(CI) = 1.15 (0.94-1.42)] or algorithm-based [OR(CI) = 1.04
      (0.89-1.21)] diagnoses. There was also no sex difference in ADHD PRS in
      individuals with ADHD diagnoses that were registry-based [OR(CI) = 1.04 (0.84
      1.30)], screening-based [OR(CI) = 0.96 (0.85-1.08)] or algorithm-based [OR(CI) =
      1.15 (0.78-1.68)]. CONCLUSIONS: This study provides genetic evidence that ADHD
      risk may be more likely to manifest or be diagnosed as anxiety or depression in
      females than in males. Contrary to some earlier studies, the results do not
      support increased ADHD genetic risk in females with ADHD as compared to affected
      males.

PMID- 29451304
TI  - Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility
      to proteasome inhibitors.
AB  - Mucinous type of epithelial ovarian cancer (MuOC) is a unique subtype with a poor
      survival outcome in recurrent and advanced stages. The role of type-specific
      epigenomics and its clinical significance remains uncertain. We analyzed the
      methylomic profiles of 6 benign mucinous adenomas, 24 MuOCs, 103 serous type of
      epithelial ovarian cancers (SeOCs) and 337 nonepithelial ovarian cancers. MuOC
      and SeOC exhibited distinct DNA methylation profiles comprising 101 genes, 81 of
      which exhibited low methylation in MuOC and were associated with the response to
      glucocorticoid, ATP hydrolysis-coupled proton transport, proteolysis involved in
      the cellular protein catabolic process and ion transmembrane transport.
      Hierarchical clustering analysis showed that the profiles of MuOC were similar to
      colorectal adenocarcinoma and stomach adenocarcinoma. Genetic interaction network
      analysis of differentially methylated genes in MuOC showed a dominant network
      module is the proteasome subunit beta (PSMB) family. Combined functional module
      and methylation analysis identified PSMB8 as a candidate marker for MuOC.
      Immunohistochemical staining of PSMB8 used to validate in 94 samples of ovarian
      tumors (mucinous adenoma, MuOC or SeOC) and 62 samples of gastrointestinal
      cancer. PSMB8 was commonly expressed in MuOC and gastrointestinal cancer samples,
      predominantly as strong cytoplasmic and occasionally weak nuclei staining, but
      was not expressed in SeOC samples. Carfilzomib, a second-generation proteasome
      inhibitor, suppressed MuOC cell growth in vitro. This study unveiled a mucinous
      type-specific methylation profile and suggests the potential use of a proteasome
      inhibitor to treat MuOC.

PMID- 29451305
TI  - Treading slowly through hypoxic waters: dichloroacetate to the rescue!

PMID- 29451307
TI  - Phenological responses to multiple environmental drivers under climate change:
      insights from a long-term observational study and a manipulative field
      experiment.
AB  - Climate change has induced pronounced shifts in the reproductive phenology of
      plants, yet we know little about which environmental factors contribute to
      interspecific variation in responses and their effects on fitness. We integrate
      data from a 43 yr record of first flowering for six species in subalpine Colorado
      meadows with a 3 yr snow manipulation experiment on the perennial forb Boechera
      stricta (Brassicaceae) from the same site. We analyze shifts in the onset of
      flowering in relation to environmental drivers known to influence phenology: the
      timing of snowmelt, the accumulation of growing degree days, and photoperiod.
      Variation in responses to climate change depended on the sequence in which
      species flowered, with early-flowering species reproducing faster, at a lower
      heat sum, and under increasingly disparate photoperiods relative to later
      flowering species. Early snow-removal treatments confirm that the timing of
      snowmelt governs observed trends in flowering phenology of B. stricta and that
      climate change can reduce the probability of flowering, thereby depressing
      fitness. Our findings suggest that climate change is decoupling historical
      combinations of photoperiod and temperature and outpacing phenological changes
      for our focal species. Accurate predictions of biological responses to climate
      change require a thorough understanding of the factors driving shifts in
      phenology.

PMID- 29451306
TI  - Supraspinal modulation of neuronal synchronization by nociceptive stimulation
      induces an enduring reorganization of dorsal horn neuronal connectivity.
AB  - KEY POINTS: The state of central sensitization induced by the intradermic
      injection of capsaicin leads to structured (non-random) changes in functional
      connectivity between dorsal horn neuronal populations distributed along the
      spinal lumbar segments in anaesthetized cats. The capsaicin-induced changes in
      neuronal connectivity and the concurrent increase in secondary hyperalgesia are
      transiently reversed by the systemic administration of small doses of lidocaine,
      a clinically effective procedure to treat neuropathic pain. The effects of both
      capsaicin and lidocaine are greatly attenuated in spinalized preparations,
      showing that supraspinal influences play a significant role in the shaping of
      nociceptive-induced changes in dorsal horn functional neuronal connectivity. We
      conclude that changes in functional connectivity between segmental populations of
      dorsal horn neurones induced by capsaicin and lidocaine result from a cooperative
      adaptive interaction between supraspinal and spinal neuronal networks, a process
      that may have a relevant role in the pathogenesis of chronic pain and analgesia.
      ABSTRACT: Despite a profusion of information on the molecular and cellular
      mechanisms involved in the central sensitization produced by intense nociceptive
      stimulation, the changes in the patterns of functional connectivity between
      spinal neurones associated with the development of secondary hyperalgesia and
      allodynia remain largely unknown. Here we show that the state of central
      sensitization produced by the intradermal injection of capsaicin is associated
      with structured transformations in neuronal synchronization that lead to an
      enduring reorganization of the functional connectivity within a segmentally
      distributed ensemble of dorsal horn neurones. These changes are transiently
      reversed by the systemic administration of small doses of lidocaine, a clinically
      effective procedure to treat neuropathic pain. Lidocaine also reduces the
      capsaicin-induced facilitation of the spinal responses evoked by weak mechanical
      stimulation of the skin in the region of secondary but not primary hyperalgesia.
      The effects of both intradermic capsaicin and systemic lidocaine on the segmental
      correlation and coherence between ongoing cord dorsum potentials and on the
      responses evoked by tactile stimulation in the region of secondary hyperalgesia
      are greatly attenuated in spinalized preparations, showing that supraspinal
      influences are involved in the reorganization of the nociceptive-induced
      structured patterns of dorsal horn neuronal connectivity. We conclude that the
      structured reorganization of the functional connectivity between the dorsal horn
      neurones induced by capsaicin nociceptive stimulation results from cooperative
      interactions between supraspinal and spinal networks, a process that may have a
      relevant role in the shaping of the spinal state in the pathogenesis of chronic
      pain and analgesia.

PMID- 29451308
TI  - Apheresis buffy coat collection without photoactivation has no effect on
      apoptosis, cell proliferation, and total viability of mononuclear cells collected
      using photopheresis systems.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) has been approved for the
      treatment of advanced cutaneous T-cell lymphoma since 1988. While the precise
      mechanisms resulting in clinical effects are not fully understood, the
      photoactivation of mononuclear cells (MNCs) using ultraviolet A (UVA) light and
      methoxsalen is believed to be the predominant initiating process. The effects of
      MNC passage through the instrument without photoactivation are unknown. The
      objective of this study was to evaluate the effect of cell processing through the
      photopheresis instruments on MNCs. STUDY DESIGN AND METHODS: Fourteen healthy
      male subjects underwent one simulated ECP procedure without reinfusion of buffy
      coats (BCs) in a two-center, open-label, prospective trial. Baseline peripheral
      blood BC, apheresis-separated untreated BC (BC1), and photoactivated BC (BC2)
      were evaluated in culture for viability by dye exclusion, apoptosis by annexin V
      binding, and cell proliferation response to phytohemagglutinin (PHA) stimulation
      by bromodeoxyuridine (BrdU) incorporation. RESULTS: Photoactivation (BC2)
      resulted in 88% expression of annexin V by Day 1 of culture compared with 37 and
      39% for baseline and untreated BC1. Cell viability by propidium iodide exclusion
      was reduced to 10% in BC2 on Day 1 versus 65 and 60% for baseline and BC1. The
      proliferative response to PHA stimulation was 97% inhibited in the photoactivated
      BC2. CONCLUSIONS: These results demonstrate that the mechanical processes used
      for cell separation and processing of the BC in the absence of photoactivation do
      not induce a significant amount of apoptosis compared to the standard ECP with
      methoxsalen and UVA photoactivation.

PMID- 29451309
TI  - Antibodies to human neutrophil antigen HNA-3b implicated in cases of neonatal
      alloimmune neutropenia.
AB  - BACKGROUND: Neonatal alloimmune neutropenia results from maternal
      alloimmunization to human neutrophil antigens. The alloantibodies involved in
      neonatal alloimmune neutropenia are against human neutrophil antigens HNA-1a, HNA
      1b, HNA-1c, HNA-1d, HNA-2, HNA-3a, HNA-4a, HNA-4b, and HNA-5a; however, to date,
      antibodies specific to HNA-3b have not been reported. STUDY DESIGN AND METHODS:
      Blood samples from 10,000 unselected neonates were analyzed, resulting in the
      selection of 88 neutropenic newborns (neutrophil count <1.5 * 109 /L) from 83
      mothers (three pairs of twins and one triplet). HNA-3 genotyping was performed by
      polymerase chain reaction-restriction fragment length polymorphism to identify
      the cases of maternal-fetal HNA-3 incompatibility. Serologic studies for
      detecting maternal HNA-3 alloantibodies were performed with the granulocyte
      agglutination test, the white blood cell immunofluorescence test, and a LABScreen
      Multi-HNA Kit. RESULTS: Genotyping studies identified 13 of 88 (14.8%) instances
      of maternal-fetal HNA-3 incompatibility, with all mothers typed as HNA-3a/a and
      neonates typed as HNA-3a/b. Serologic studies revealed that five of 13 (38.5%)
      mothers carried anti-HNA-3b plus human leukocyte antigen antibodies and that
      three of 13 (23.1%) mothers had anti-HNA-3b without human leukocyte antigen
      antibodies. CONCLUSION: Here, we report the first three cases of neonatal
      alloimmune neutropenia associated with HNA-3b antibodies resulting in a neonatal
      alloimmune neutropenia incidence of one in 3333 live births.

PMID- 29451311
TI  - Impaired phloem loading in zmsweet13a,b,c sucrose transporter triple knock-out
      mutants in Zea mays.
AB  - Crop yield depends on efficient allocation of sucrose from leaves to seeds. In
      Arabidopsis, phloem loading is mediated by a combination of SWEET sucrose
      effluxers and subsequent uptake by SUT1/SUC2 sucrose/H+ symporters. ZmSUT1 is
      essential for carbon allocation in maize, but the relative contribution to
      apoplasmic phloem loading and retrieval of sucrose leaking from the translocation
      path is not known. Here we analysed the contribution of SWEETs to phloem loading
      in maize. We identified three leaf-expressed SWEET sucrose transporters as key
      components of apoplasmic phloem loading in Zea mays L. ZmSWEET13 paralogues (a,
      b, c) are among the most highly expressed genes in the leaf vasculature. Genome
      edited triple knock-out mutants were severely stunted. Photosynthesis of mutants
      was impaired and leaves accumulated high levels of soluble sugars and starch. RNA
      seq revealed profound transcriptional deregulation of genes associated with
      photosynthesis and carbohydrate metabolism. Genome-wide association study (GWAS)
      analyses may indicate that variability in ZmSWEET13s correlates with agronomical
      traits, especifically flowering time and leaf angle. This work provides support
      for cooperation of three ZmSWEET13s with ZmSUT1 in phloem loading in Z. mays.

PMID- 29451310
TI  - Interatrial block predicts silent atrial fibrillation episodes detected by
      cardiac implantable electronic devices.

PMID- 29451312
TI  - YODA MAP3K kinase regulates plant immune responses conferring broad-spectrum
      disease resistance.
AB  - Mitogen-activated protein kinases (MAPKs) cascades play essential roles in plants
      by transducing developmental cues and environmental signals into cellular
      responses. Among the latter are microbe-associated molecular patterns perceived
      by pattern recognition receptors (PRRs), which trigger immunity. We found that
      YODA (YDA) - a MAPK kinase kinase regulating several Arabidopsis developmental
      processes, like stomatal patterning - also modulates immune responses. Resistance
      to pathogens is compromised in yda alleles, whereas plants expressing the
      constitutively active YDA (CA-YDA) protein show broad-spectrum resistance to
      fungi, bacteria, and oomycetes with different colonization modes. YDA functions
      in the same pathway as ERECTA (ER) Receptor-Like Kinase, regulating both immunity
      and stomatal patterning. ER-YDA-mediated immune responses act in parallel to
      canonical disease resistance pathways regulated by phytohormones and PRRs. CA-YDA
      plants exhibit altered cell-wall integrity and constitutively express defense
      associated genes, including some encoding putative small secreted peptides and
      PRRs whose impairment resulted in enhanced susceptibility phenotypes. CA-YDA
      plants show strong reprogramming of their phosphoproteome, which contains protein
      targets distinct from described MAPKs substrates. Our results suggest that, in
      addition to stomata development, the ER-YDA pathway regulates an immune
      surveillance system conferring broad-spectrum disease resistance that is distinct
      from the canonical pathways mediated by described PRRs and defense hormones.

PMID- 29451314
TI  - Aortic Diameters and Mild Functional Aortic Regurgitation in Hypertensive and
      Normotensive People: Do They Carry the Same Meaning?
AB  - OBJECTIVES: The association between the aortic root diameter and aortic
      regurgitation in hypertensive and normotensive people is still disputed, and the
      underlying mechanisms remain to be clearly elucidated. We aimed to investigate
      the relationship between the aortic root diameter and trivial to mild functional
      aortic regurgitation in never-treated hypertensive patients with a new diagnosis
      compared with healthy normotensive participants. METHODS: A total of 182
      hypertensives and 232 age-matched normotensives were included in the study.
      Anthropometric and office blood pressure (BP) measurements, echocardiography, and
      a carotid stiffness assessment were performed in all of the participants. Aortic
      measures for the annulus, sinuses of Valsalva, sinotubular junction, and
      ascending aorta were taken in late diastole according to the leading-edge method.
      RESULTS: The mean age of all participants was 52 years. Hypertensive patients had
      a significantly higher body surface area, mean arterial pressure, and pulse
      pressure (P < .0001) than normotensive participants. Annulus and sinotubular
      junction diameters adjusted for confounders and indexed to the body surface area
      were significantly higher in normotensives than in hypertensives. The prevalence
      of functional aortic regurgitation was higher in hypertensives (34.8% versus
      15.4%; P < .0001). Among the hypertensives, no difference in aortic diameters was
      found between patients with or without functional aortic regurgitation, whereas
      normotensives with functional aortic regurgitation had larger aortic root
      diameters. Aging and BP among the hypertensives were the main determinants of
      functional aortic regurgitation. CONCLUSIONS: Hypertensive patients had a smaller
      indexed aortic root diameter than normotensive participants but had a higher
      prevalence of trivial to mild functional aortic regurgitation. The aging process
      is the main determinant of functional aortic regurgitation in both groups, but
      high BP also plays an important role in hypertensives.

PMID- 29451313
TI  - Drivers and mechanisms of tree mortality in moist tropical forests.
AB  - Tree mortality rates appear to be increasing in moist tropical forests (MTFs)
      with significant carbon cycle consequences. Here, we review the state of
      knowledge regarding MTF tree mortality, create a conceptual framework with
      testable hypotheses regarding the drivers, mechanisms and interactions that may
      underlie increasing MTF mortality rates, and identify the next steps for improved
      understanding and reduced prediction. Increasing mortality rates are associated
      with rising temperature and vapor pressure deficit, liana abundance, drought,
      wind events, fire and, possibly, CO2 fertilization-induced increases in stand
      thinning or acceleration of trees reaching larger, more vulnerable heights. The
      majority of these mortality drivers may kill trees in part through carbon
      starvation and hydraulic failure. The relative importance of each driver is
      unknown. High species diversity may buffer MTFs against large-scale mortality
      events, but recent and expected trends in mortality drivers give reason for
      concern regarding increasing mortality within MTFs. Models of tropical tree
      mortality are advancing the representation of hydraulics, carbon and demography,
      but require more empirical knowledge regarding the most common drivers and their
      subsequent mechanisms. We outline critical datasets and model developments
      required to test hypotheses regarding the underlying causes of increasing MTF
      mortality rates, and improve prediction of future mortality under climate change.

PMID- 29451315
TI  - Sensitivity to the Sampling Process Emerges From the Principle of Efficiency.
AB  - Humans can seamlessly infer other people's preferences, based on what they do.
      Broadly, two types of accounts have been proposed to explain different aspects of
      this ability. The first account focuses on spatial information: Agents' efficient
      navigation in space reveals what they like. The second account focuses on
      statistical information: Uncommon choices reveal stronger preferences. Together,
      these two lines of research suggest that we have two distinct capacities for
      inferring preferences. Here we propose that this is not the case, and that
      spatial-based and statistical-based preference inferences can be explained by the
      assumption that agents are efficient alone. We show that people's sensitivity to
      spatial and statistical information when they infer preferences is best predicted
      by a computational model of the principle of efficiency, and that this model
      outperforms dual-system models, even when the latter are fit to participant
      judgments. Our results suggest that, as adults, a unified understanding of agency
      under the principle of efficiency underlies our ability to infer preferences.

PMID- 29451316
TI  - Time to step-up the fight against NAFLD.

PMID- 29451317
TI  - Ultrasound-Guided Microinvasive Carpal Tunnel Release Using a Novel Retractable
      Needle-Mounted Blade: A Cadaveric Study.
AB  - Ultrasound (US)-guided microinvasive procedures are defined as those performed
      via needles without notable scarring. Ten cadaver hands underwent US-guided
      microinvasive carpal tunnel release using a novel needle-based tool, the micro i
      Blade (Summit Medical Products, Inc, Sandy, UT). A US-imaged landmark, the
      inflexion point of the ligaments distal to the hook of the hamate, was used to
      position the distal extent of the cut. The transverse carpal ligament was
      successfully released in all hands without damage to nerves or arteries. In 3
      specimens, the fascia between the thenar and hypothenar muscles was partly
      preserved, whereas the palmar aponeurosis was partly cut in 1 specimen. The micro
      i-Blade with the cutting knife retracted was also useful as a probe palpated
      through the palm of the cadaver hand, to test the release of the transverse
      carpal ligament and to guide the procedure.

PMID- 29451318
TI  - Effective management of severe cutaneous mastocytosis in young children with
      omalizumab (Xolair(r) ).
AB  - Omalizumab (Xolair(r) ) is an anti-IgE monoclonal antibody, which may benefit
      adults with systemic mastocytosis. We report effective treatment with omalizumab
      in two toddlers with severe diffuse cutaneous mastocytosis. Our cases offer
      preliminary evidence to support the safe use of omalizumab in paediatric patients
      with cutaneous mastocytosis.

PMID- 29451319
TI  - Prognosis in myelodysplastic syndromes: The attractions and limitations of
      simplicity.

PMID- 29451320
TI  - Commentary on the EMA Guideline on strategies to identify and mitigate risks for
      first-in-human and early clinical trials with investigational medicinal products.

PMID- 29451322
TI  - Intuitive Probabilities and the Limitation of Moral Imagination.
AB  - There is a vast literature that seeks to uncover features underlying moral
      judgment by eliciting reactions to hypothetical scenarios such as trolley
      problems. These thought experiments assume that participants accept the outcomes
      stipulated in the scenarios. Across seven studies (N = 968), we demonstrate that
      intuition overrides stipulated outcomes even when participants are explicitly
      told that an action will result in a particular outcome. Participants instead
      substitute their own estimates of the probability of outcomes for stipulated
      outcomes, and these probability estimates in turn influence moral judgments. Our
      findings demonstrate that intuitive likelihoods are one critical factor in moral
      judgment, one that is not suspended even in moral dilemmas that explicitly
      stipulate outcomes. Features thought to underlie moral reasoning, such as
      intention, may operate, in part, by affecting the intuitive likelihood of
      outcomes, and, problematically, moral differences between scenarios may be
      confounded with non-moral intuitive probabilities.

PMID- 29451321
TI  - Predicting recovery in acute poststroke aphasia.
AB  - OBJECTIVE: Many stroke patients show remarkable recovery of language after
      initial severe impairment, but it is difficult to predict which patients will
      show good recovery. We aimed to identify patient and lesion characteristics that
      together predict the best naming outcome in 4 studies. METHODS: We report 2
      longitudinal studies that identified 2 variables at onset that were strongly
      associated with good recovery of naming (the most common residual deficit in
      aphasia) in the first 6 months after stroke: damage to left posterior superior
      temporal gyrus (pSTG) and/or superior longitudinal fasciculus/arcuate fasciculus
      (SLF/AF), and selective serotonin reuptake inhibitor (SSRI) use. We then tested
      these variables in 2 independent cohorts of chronic left hemisphere stroke
      patients, using chi-square tests and multivariate logistic regression for
      dichotomous outcomes and t tests for continuous outcomes. RESULTS: Lesion load in
      left pSTG and SLF/AF was associated with poorer naming outcome. Preservation of
      these areas and use of SSRIs were associated with naming recovery, independent of
      lesion volume, time since stroke, and depression. Patients with damage to these
      critical areas showed better naming outcome if they took SSRIs for 3 months after
      stroke. Those with preservation of these critical areas achieved good recovery of
      naming regardless of SSRI use. INTERPRETATION: Lesion load in left pSTG and
      SLF/AF at onset predicts later naming performance. Although based on a small
      number of patients, our preliminary results suggest outcome might be modulated by
      SSRIs, but these associations need to be confirmed in a larger randomized
      controlled trial. Ann Neurol 2018;83:612-622.

PMID- 29451324
TI  - Reply.

PMID- 29451323
TI  - [18 F]AV-1451 tau-PET and primary progressive aphasia.
AB  - OBJECTIVES: To assess [18 F]AV-1451 tau-PET (positron emission tomography) uptake
      patterns across the primary progressive aphasia (PPA) variants (logopenic,
      semantic, and agrammatic), examine regional uptake patterns of [18 F]AV-1451
      independent of clinical diagnosis, and compare the diagnostic utility of [18 F]AV
      1451, [18 F]-fluorodeoxygluclose (FDG)-PET and MRI (magnetic resonance imaging)
      to differentiate the PPA variants. METHODS: We performed statistical parametric
      mapping of [18 F]AV-1451 across 40 PPA patients (logopenic-PPA = 14, semantic-PPA
      = 13, and agrammatic-PPA = 13) compared to 80 cognitively normal, Pittsburgh
      compound B-negative controls, age and gender matched 2:1. Principal component
      analysis of regional [18 F]AV-1451 tau-PET standard uptake value ratio was
      performed to understand underlying patterns of [18 F]AV-1451 uptake independent
      of clinical diagnosis. Penalized multinomial regression analyses were utilized to
      assess diagnostic utility. RESULTS: Logopenic-PPA showed striking uptake
      throughout neocortex, particularly temporoparietal, compared to controls,
      semantic-PPA, and agrammatic-PPA. Semantic-PPA and agrammatic-PPA showed milder
      patterns of focal [18 F]AV-1451 uptake. Semantic-PPA showed elevated uptake
      (left>right) in anteromedial temporal lobes, compared to controls and agrammatic
      PPA. Agrammatic-PPA showed elevated uptake (left>right) throughout prefrontal
      white matter and in subcortical gray matter structures, compared to controls and
      semantic-PPA. The principal component analysis of regional [18 F]AV-1451
      indicated two primary dimensions, a severity dimension that distinguished
      logopenic-PPA from agrammatic-PPA and semantic-PPA, and a frontal versus temporal
      contrast that distinguishes agrammatic-PPA and semantic-PPA cases. Diagnostic
      utility of [18 F]AV-1451was superior to MRI and at least equal to FDG-PET.
      INTERPRETATION: [18 F]AV-1451binding characteristics differ across the PPA
      variants and were excellent at distinguishing between the variants. [18 F]AV
      1451binding characteristics were as good or better than other brain imaging
      modalities utilized in clinical practice, suggesting that [18 F]AV-1451 may have
      clinical diagnostic utility in PPA. Ann Neurol 2018 Ann Neurol 2018;83:599-611.

PMID- 29451325
TI  - Purine-Derived Nitroxides for Noncovalent Spin-Labeling of Abasic Sites in Duplex
      Nucleic Acids.
AB  - A series of purine-based spin labels was prepared for noncovalent spin-labeling
      of abasic sites of duplex nucleic acids through hydrogen bonding to an orphan
      base on the opposing strand and pi-stacking interactions with the flanking bases.
      Both 1,1,3,3-tetramethylisoindolin-2-yloxyl and 2,2,6,6-tetramethylpiperidine-1
      oxyl (TEMPO) were conjugated to either the C2- or C6-position of the purines,
      yielding nitroxide derivatives of guanine, adenine, or 2,6-diaminopurine. The
      isoindoline-derived spin labels showed extensive or full binding to abasic sites
      in RNA duplexes, whereas the TEMPO-derived spin labels showed limited binding. An
      adenine-derived spin label (5) bound fully at low temperature to abasic sites in
      both DNA and RNA duplexes when paired with thymine and uracil, respectively,
      complementing the previously described guanine-derived spin label G, which binds
      efficiently opposite cytosine. Compound G was also shown to bind to abasic sites
      in DNA-RNA hybrids, either in the DNA- or the RNA-strand. G showed only a minor
      flanking-sequence effect upon binding to abasic sites in RNA. When the abasic
      site was placed close to the end of the RNA duplex, the affinity of the spin
      label G was reduced; full binding was observed at the fourth position from the
      duplex end. In summary, spin labels 5 and G showed full binding to abasic sites
      in both DNA and RNA duplexes and are promising spin labels for structural studies
      of nucleic acids by pulsed EPR methods.

PMID- 29451326
TI  - Evaluation of factors contributing to the decline in exclusive breastfeeding at 6
      months postpartum: The 2011-2016 National Surveys in Taiwan.
AB  - BACKGROUND: Since 1992, breastfeeding promotion in Taiwan considerably raised the
      breastfeeding rates; however, more recent surveillance showed that breastfeeding
      indicators stagnated or even decreased. METHODS: We analyzed 6 cross-sectional
      national surveys of 69 159 postpartum women to examine the breastfeeding trends
      at 6 months postpartum during 2011-2016 in Taiwan and the contributing role of
      maternal and environmental factors. Data were collected through telephone
      interviews, using structured questionnaires with randomly selected mothers, who
      gave birth in those years. A multinomial logistic regression was used to analyze
      the data. RESULTS: Partial breastfeeding rates at 6 months postpartum increased
      from 2011 to 2016 (25.4%-45.1%, crude odds ratio [OR] = 1.14 per year of study);
      however, the rates of exclusive breastfeeding at 6 months postpartum declined
      (24.5%-14.8%, crude OR = 0.91 per year of study). During this period, increases
      in maternal age and educational level, employment outside the house, and
      prepregnancy obesity were observed. Despite a growing number of births at
      certified baby-friendly hospitals, fewer mothers experienced early skin-to-skin
      contact and rooming-in in 2016 than in 2011. Adjustment for breastfeeding-related
      factors did not appreciably change the odds ratio for year of birth. Prenatal
      intention to breastfeed was most strongly associated with breastfeeding at 6
      months postpartum (OR > 5). CONCLUSIONS: Maternal and environmental factors in
      the study could not explain the decline in exclusive breastfeeding. The decline
      in exclusive breastfeeding, accompanying the increase in partial breastfeeding,
      suggests that more support is needed for mothers who intend to breastfeed
      exclusively.

PMID- 29451328
TI  - Change and Stability of Emotional Health of Rural Pennsylvania Youth During High
      School.
AB  - PURPOSE: Few prior studies have examined change in emotional health of high
      school students in a rural context. Considering the multifaceted nature of
      emotional health, this research aims to identify the patterns and explore change
      and stability of the emotional health of rural Pennsylvania youth. It also
      investigates the influence of family, peers, school, and the community
      environment on rural adolescents' emotional health. METHODS: Using panel data
      from the Rural Youth Education Project, we employed latent transition analysis to
      examine changes in patterns of rural students' self-reported emotional health
      from 9th grade to 11th grade (N = 1,294). FINDINGS: Four distinct emotional
      health subgroups for rural adolescents were identified. Over half of the youth in
      the sample felt emotionally well, or positive, in both 9th and 11th grades.
      Roughly 60% of rural youth remained in the same emotional health category from
      9th to 11th grade, but a substantial minority experienced change in emotional
      health. One-fifth reported lower emotional health status in 11th grade, and one
      fifth indicated more positive emotions in 11th than in 9th grade. We found strong
      evidence of family, school, community, and peer influences on the emotional
      health of rural youth in 9th grade. CONCLUSIONS: The results suggest that while a
      large share of rural youth exhibit positive emotional health and remain positive
      across their high school years, a substantial share of rural youth experience
      changing emotional health. The study underscores the important role that family,
      peers, school, and the community environment play for rural youth's emotional
      health over time.

PMID- 29451327
TI  - MicroRNA-365 modulates astrocyte conversion into neuron in adult rat brain after
      stroke by targeting Pax6.
AB  - Reactive astrocytes induced by ischemia can transdifferentiate into mature
      neurons. This neurogenic potential of astrocytes may have therapeutic value for
      brain injury. Epigenetic modifications are widely known to involve in
      developmental and adult neurogenesis. PAX6, a neurogenic fate determinant,
      contributes to the astrocyte-to-neuron conversion. However, it is unclear whether
      microRNAs (miRs) modulate PAX6-mediated astrocyte-to-neuron conversion. In the
      present study we used bioinformatic approaches to predict miRs potentially
      targeting Pax6, and transient middle cerebral artery occlusion (MCAO) to model
      cerebral ischemic injury in adult rats. These rats were given striatal injection
      of glial fibrillary acidic protein targeted enhanced green fluorescence protein
      lentiviral vectors (Lv-GFAP-EGFP) to permit cell fate mapping for tracing
      astrocytes-derived neurons. We verified that miR-365 directly targets to the 3'
      UTR of Pax6 by luciferase assay. We found that miR-365 expression was
      significantly increased in the ischemic brain. Intraventricular injection of miR
      365 antagomir effectively increased astrocytic PAX6 expression and the number of
      new mature neurons derived from astrocytes in the ischemic striatum, and reduced
      neurological deficits as well as cerebral infarct volume. Conversely, miR-365
      agomir reduced PAX6 expression and neurogenesis, and worsened brain injury.
      Moreover, exogenous overexpression of PAX6 enhanced the astrocyte-to-neuron
      conversion and abolished the effects of miR-365. Our results demonstrate that
      increase of miR-365 in the ischemic brain inhibits astrocyte-to-neuron conversion
      by targeting Pax6, whereas knockdown of miR-365 enhances PAX6-mediated
      neurogenesis from astrocytes and attenuates neuronal injury in the brain after
      ischemic stroke. Our findings provide a foundation for developing novel
      therapeutic strategies for brain injury.

PMID- 29451330
TI  - Simple methods to optimize the success in microsurgical submandibular gland
      transplantation for the treatment of patients with keratoconjunctivitis.

PMID- 29451329
TI  - High spatiotemporal resolution bSSFP imaging of hyperpolarized [1-13 C]pyruvate
      and [1-13 C]lactate with spectral suppression of alanine and pyruvate-hydrate.
AB  - PURPOSE: The balanced steady-state free precession (bSSFP) acquisition enables
      high spatiotemporal resolution for hyperpolarized 13 C MRI at 3T but is limited
      by spectral contamination from adjacent resonances. The purpose of this study was
      to develop a framework for in vivo dynamic high resolution imaging of
      hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate generated in vivo at 3T by
      simplifying the spectrum through the use of selective suppression pulses.
      METHODS: Spectral suppression pulses were incorporated into the bSSFP sequence
      for suppression of [1-13 C]alanine and [1-13 C]pyruvate-hydrate signals, leaving
      only the pyruvate and lactate resonances. Subsequently, the bSSFP pulse width,
      time-bandwidth, and repetition time were optimized for imaging these dual
      resonances. RESULTS: The spectral suppression reduced both the alanine and
      pyruvate-hydrate signals by 85.5 +/- 4.9% and had no significant effect on
      quantitation of pyruvate to lactate conversion (liver: P = 0.400, kidney: P =
      0.499). High resolution (2 * 2 mm2 and 3 * 3 mm2 ) subsecond 2D coronal
      projections and 3D 2.5 mm isotropic images were obtained in rats and tumor
      bearing mice with 1.8-5 s temporal resolution, allowing for calculation of
      lactate-to-pyruvate ratios and kPL . CONCLUSION: The developed framework
      presented here shows the capability for dynamic high resolution volumetric
      hyperpolarized bSSFP imaging of pyruvate-to-lactate conversion on a clinical 3T
      MR scanner.

PMID- 29451331
TI  - Sliding free transverse rectus abdominis myocutaneous flap for closure of a
      massive abdominal wall defect: A case report.
AB  - Despite considerable advances in reconstructive surgery, massive abdominal wall
      defects continue to pose a significant surgical challenge. We report the case of
      a 72-year-old morbidly obese female patient with Clostridium septicum-related gas
      gangrene of the abdominal wall. After multidisciplinary treatment and multiple
      extensive debridements, a massive full-thickness defect (40 cm * 35 cm) of the
      right abdominal wall was present. The abdominal contents were covered with a
      resorbable mesh to prevent evisceration. Finally, the composite defect was
      successfully reconstructed through a contralateral extended free transverse
      rectus abdominis myocutaneus (TRAM) flap (50 cm * 38 cm). An arterio-venous loop
      to the superficial femoral vessels using the great saphenous vein was necessary
      to allow the flap to reach the defect. Postoperatively, a minor wound healing
      disorder of the flap was successfully treated with split skin grafting. Six month
      after surgery, the patient presented with a completely healed flap coverage area
      and a small abdominal hernia without the need of further surgical revision. This
      case illustrates the use of a sliding free TRAM flap for closure of a massive
      abdominal wall defect.

PMID- 29451332
TI  - Characterizing the Effects of a "Switchable Water" Additive on the Aqueous
      Solubility of Small Molecules.
AB  - "Switchable water" is an aqueous solution containing a water-soluble amine
      additive that exhibits CO2 -switchable properties, such as large changes in ionic
      strength, by forming an ammonium bicarbonate salt. Switchable water has been used
      to reversibly "salt-out" organic compounds from water. This study explores the
      salting out of several compounds in switchable water when CO2 is present and also
      explores the solubility of small molecules in switchable water, compared to pure
      water, when CO2 is absent. The results show that organic compounds are generally
      more soluble in switchable water than pure water in the absence of CO2 , but less
      soluble in the presence of 1 atm CO2 . Exceptions include carboxylic acids and
      phenols which, presumably due to their acidity, are more soluble in switchable
      water than in pure water, even when CO2 is applied. Kirkwood-Buff solvation
      theory was applied to gain insights into the effects of the amine additive on the
      aqueous solubility of caffeine. Furthermore, the switchable properties of the
      additives allow for the preparation of switchable aqueous two-phase systems.

PMID- 29451333
TI  - Urban-Rural Differences in Aerobic Physical Activity, Muscle Strengthening
      Exercise, and Screen-Time Sedentary Behavior.
AB  - PURPOSE: Compared to their urban counterparts, US residents in rural settings
      face an increased risk of premature mortality and health problems that have been
      linked to insufficient physical activity (PA) levels. There is limited literature
      regarding urban-rural differences in adherence to national guidelines for all 3
      PA-related behaviors. METHODS: We investigated urban-rural differences in aerobic
      PA, leisure-time muscle strengthening PA, and leisure screen-time sedentary
      behavior in a combined data set of the 2011-2014 waves (N = 14,188) of the
      nationally representative National Cancer Institute's Health Information National
      Trends Survey. FINDINGS: We found no evidence of a difference between large urban
      and rural residents' aerobic PA levels. The typical number of weekly bouts of
      leisure-time muscle strengthening PA was 25% lower for rural residents (incidence
      rate ratio [IRR] = 0.751, P < .001); this relationship was no longer
      statistically significant after controlling for potentially confounding
      covariates. In adjusted models, we found rural residents to engage in 6.6% less
      daily leisure screen-time sedentary behavior than their large urban counterparts
      (IRR = 0.934, P = .031). CONCLUSIONS: Taken together with previous literature,
      these results suggest that rural residents may engage in comparable levels of
      total PA, but less leisure-time PA, than their urban counterparts.

PMID- 29451334
TI  - microRNA profiling between Bacillus thuringiensis Cry1Ab-susceptible and 
      resistant European corn borer, Ostrinia nubilalis (Hubner).
AB  - Transgenic maize hybrids that express insecticidal Bacillus thuringiensis (Bt)
      crystalline (Cry) protein toxins effectively protect against the European corn
      borer, Ostrinia nubilalis, a devastating maize pest. Field monitoring and
      laboratory selections have detected varying levels of O. nubilalis resistance to
      Cry1Ab toxin. MicroRNAs (miRNAs) are short noncoding RNAs that are involved in
      post-transcriptional gene regulation. Their potential roles in the evolution of
      Bt resistance, however, remain largely unknown. Sequencing of small RNA libraries
      from the midgut of Cry1Ab-susceptible and resistant O. nubilalis larvae resulted
      in the discovery of 277 miRNAs, including 248 conserved and 29 novel. Comparative
      analyses of miRNA expression profiles between the laboratory strains predicted 26
      and nine significantly up- and down-regulated transcripts, respectively, in the
      midgut of Cry1Ab resistant larvae. Amongst 15 differentially regulated miRNAs
      examined by quantitative real-time PCR, nine (60%) were validated as
      cosegregating with Cry1Ab resistance in a backcross progeny. Differentially
      expressed miRNAs were predicted to affect transcripts involved in cell membrane
      components with functions in metabolism and binding, and the putative Bt
      resistance genes aminopeptidase N and cadherin. These results lay the foundation
      for future investigation of the potential role of miRNAs in the evolution of Bt
      resistance.

PMID- 29451335
TI  - Mesenchymal Stem Cells Protect Against Hypoxia-Ischemia Brain Damage by Enhancing
      Autophagy Through Brain Derived Neurotrophic Factor/Mammalin Target of Rapamycin
      Signaling Pathway.
AB  - Hypoxic-ischemic encephalopathy (HIE) is a serious disease for neonates. However,
      present therapeutic strategies are not effective enough for treating HIE.
      Previous study showed that mesenchymal stem cells (MSCs) can exert
      neuroprotective effects for brain damage, but its mechanism remains elusive.
      Using in vitro coculture of rat cortical primary neurons and MSCs in HI
      conditions, we demonstrated that MSCs help increase brain derived neurotrophic
      factor (BDNF) and autophagy markers (LC3II and Beclin1) in the cultures and
      decrease cells death (lactate dehydrogenase levels). We demonstrated a similar
      mechanism using an in vivo rat model of HI in combination with MSCs
      transplantation. Using a behavioral study, we further showed that MSCs
      transplantation into the rat brain after HI injury can attenuate behavioral
      deficits. Finally, we found that the increase in BDNF and autophagy related
      factors after HI injury combined with MSCs transplantation can be reversed by
      anti-BDNF treatment and strengthen the point that the protective effects of BDNF
      work through inhibition of the mammalin target of rapamycin (mTOR) pathway.
      Collectively, we proposed that coculture/transplantation of MSCs after HI injury
      leads to increased BDNF expression and a subsequent reduction in mTOR pathway
      activation that results in increased autophagy and neuroprotection. This finding
      gives a hint to explore new strategies for treating neonates with HIE. Stem Cells
      2018;36:1109-1121.

PMID- 29451336
TI  - Electronically Unsaturated Three-Coordinate Aluminum Hydride and Organoaluminum
      Cations.
AB  - New three-coordinate and electronically unsaturated aluminum hydride [LAlH]+
      [HB(C6 F5 )3 ]- (LH=[{(2,6-iPr2 C6 H3 N)P(Ph2 )}2 N]H) and aluminum methyl
      [LAlMe]+ [MeB(C6 F5 )3 ]- cations have been prepared. The quantitative estimation
      of Lewis acidity by Gutmann-Beckett method revealed [LAlH]+ [HB(C6 F5 )3 ]- to be
      better Lewis acid than B(C6 F5 )3 and AlCl3 making these compounds ideal
      catalysts for Lewis acid-mediated reactions. To highlight that the work is of
      fundamental importance, catalytic hydroboration of aliphatic and aromatic
      aldehydes and ketones have been demonstrated. Important steps of the catalytic
      cycle have been probed by using multinuclear NMR measurements, including
      successful characterization of the proposed aluminum benzyloxide cationic
      intermediate, [LAl-O-CH2 Ph]+ [HB(C6 F5 )3 ]- . The proposed catalytic cycle has
      been found to be consistent with experimental observations and computational
      studies clearly indicating the migration of hydride from cationic aluminum center
      to the carbonyl carbon is the rate-limiting step of the catalytic cycle.

PMID- 29451337
TI  - Eosinophil-derived exosomes contribute to asthma remodelling by activating
      structural lung cells.
AB  - BACKGROUND: Eosinophils, a central factor in asthma pathogenesis, have the
      ability to secrete exosomes. However, the precise role played by exosomes in the
      biological processes leading up to asthma has not been fully defined. OBJECTIVE:
      We hypothesized that exosomes released by eosinophils contribute to asthma
      pathogenesis by activating structural lung cells. METHODS: Eosinophils from
      asthmatic patients and healthy volunteers were purified from peripheral blood,
      and exosomes were isolated from eosinophils of asthmatic and healthy individuals.
      All experiments were performed with eosinophil-derived exosomes from healthy and
      asthmatic subjects. Epithelial damage was evaluated using primary small airway
      epithelial cell lines through 2 types of apoptosis assays, that is, flow
      cytometry and TUNEL assay with confocal microscopy. Additionally, the epithelial
      repair was analysed by performing wound healing assays with epithelial cells.
      Functional studies such as proliferation and inhibition-proliferation assays were
      carried out in primary bronchial smooth muscle cell lines. Also, gene expression
      analysis of pro-inflammatory molecules was evaluated by real-time PCR on
      epithelial and muscle cells. Lastly, protein expression of epithelial and muscle
      cell signalling factors was estimated by Western blot. RESULTS: Asthmatic
      eosinophil-derived exosomes induced an increase in epithelial cell apoptosis at
      24 hour and 48 hour, impeding wound closure. In addition, muscle cell
      proliferation was increased at 72 hours after exosome addition and was linked
      with higher phosphorylation of ERK1/2. We also found higher expression of several
      genes when both cell types were cultured in the presence of exosomes from
      asthmatics: CCR3 and VEGFA in muscle cells, and CCL26, TNF and POSTN in
      epithelial cells. Healthy eosinophil-derived exosomes did not exert any effect
      over these cell types. CONCLUSIONS AND CLINICAL RELEVANCE: Eosinophil-derived
      exosomes from asthmatic patients participate actively in the development of the
      pathological features of asthma via structural lung cells.

PMID- 29451338
TI  - Can dimedone be used to study selenoproteins? An investigation into the
      reactivity of dimedone toward oxidized forms of selenocysteine.
AB  - Dimedone is a widely used reagent to assess the redox state of cysteine
      containing proteins as it will alkylate sulfenic acid residues, but not sulfinic
      acid residues. While it has been reported that dimedone can label selenenic acid
      residues in selenoproteins, we investigated the stability, and reversibility of
      this label in a model peptide system. We also wondered whether dimedone could be
      used to detect seleninic acid residues. We used benzenesulfinic acid,
      benzeneseleninic acid, and model selenocysteine-containing peptides to
      investigate possible reactions with dimedone. These peptides were incubated with
      H2 O2 in the presence of dimedone and then the reactions were followed by liquid
      chromatography/electrospray ionization mass spectrometry (LC/ESI-MS). The native
      peptide, H-PTVTGCUG-OH (corresponding to the native amino acid sequence of the C
      terminus of mammalian thioredoxin reductase), could not be alkylated by dimedone,
      but could be carboxymethylated with iodoacetic acid. However the "mutant
      peptide," H-PTVTGAUG-OH, could be labeled with dimedone at low concentrations of
      H2 O2 , but the reaction was reversible by addition of thiol. Due to the
      reversible nature of this alkylation, we conclude that dimedone is not a good
      reagent for detecting selenenic acids in selenoproteins. At high concentrations
      of H2 O2 , selenium was eliminated from the peptide and a dimeric form of
      dimedone could be detected using LCMS and 1 H NMR. The dimeric dimedone product
      forms as a result of a seleno-Pummerer reaction with Sec-seleninic acid. Overall
      our results show that the reaction of dimedone with oxidized cysteine residues is
      quite different from the same reaction with oxidized selenocysteine residues.

PMID- 29451339
TI  - An Indispensable Role of Androgen Receptor in Wnt Responsive Cells During
      Prostate Development, Maturation, and Regeneration.
AB  - Androgen signaling is essential for prostate development, morphogenesis, and
      regeneration. Emerging evidence indicates that Wnt/beta-catenin signaling also
      contributes to prostate development specifically through regulation of cell fate
      determination. Prostatic Axin2-expressing cells are able to respond to Wnt
      signals and possess the progenitor properties to regenerate prostatic epithelium.
      Despite critical roles of both signaling pathways, the biological significance of
      androgen receptor (AR) in Axin2-expressing/Wnt-responsive cells remains largely
      unexplored. In this study, we investigated this important question using a series
      of newly generated mouse models. Deletion of Ar in embryonic Axin2-expressing
      cells impaired early prostate development in both ex vivo and tissue implantation
      experiments. When Ar expression was deleted in prostatic Axin2-expressing cells
      at pre-puberty stages, it results in smaller and underdeveloped prostates. A
      subpopulation of Axin2 expressing cells in prostate epithelium is resistant to
      castration and, following androgen supplementation, is capable to expand to
      prostatic luminal cells. Deletion of Ar in these Axin2-expressing cells reduces
      their regenerative ability. These lines of evidence demonstrate an indispensable
      role for the Ar in Wnt-responsive cells during the course of prostate
      development, morphogenesis, and regeneration, which also imply an underlying
      interaction between the androgen and Wnt signaling pathways in the mouse
      prostate. Stem Cells 2018;36:891-902.

PMID- 29451341
TI  - Validation of acute kidney injury according to the modified KDIGO criteria in
      infants after cardiac surgery for congenital heart disease.
AB  - AIM: We aimed to validate the incidence of, risk factors for, and postoperative
      outcomes of acute kidney injury (AKI) according to the modified Kidney Disease
      Improving Global Outcomes (m-KDIGO) criteria and compare this criteria with both
      the pediatric Risk, Injury, Failure, Loss, End-stage disease (pRIFLE) and Acute
      Kidney Injury Network (AKIN) criteria in infants after cardiac surgery. METHODS:
      We retrospectively enrolled 145 consecutive infants who underwent open-heart
      surgery at Kagoshima University Hospital. RESULTS: AKI was present in 55 (37.9%),
      111 (75.9%), and 95 (65.5%) patients according to the m-KDIGO, pRIFLE, and AKIN
      criteria, respectively. Among these, 71.9% of patients pRIFLE Risk patients and
      60.5% of AKIN 1 patients were categorised in the 'no-AKI' group according to the
      m-KDIGO criteria. Low body weight (m-KDIGO odds ratio [OR], 0.73; P = 0.015;
      pRIFLE OR, 0.66; P = 0.001; AKIN OR 0.69, P = 0.002) and prolonged cross-clamp
      time (m-KDIGO OR, 1.02; <P = 0.001; pRIFLE OR, 1.02; P = 0.003; AKIN OR, 1.02; P
      = 0.001) were independent risk factors for the development of AKI. Further, m
      KDIGO-based AKI grade was more strongly associated with higher incidence of
      requiring renal replacement therapy and mortality than both the pRIFLE- and AKIN-
      based AKI grade. CONCLUSION: Application of the 3 criteria resulted in different
      AKI incidences, but each criterion could be useful for detecting risk factors for
      AKI. Notably, using m-KDIGO criteria provides more important subsequent
      postoperative outcomes. The m-KDIGO AKI criteria describe clinically relevant AKI
      in infants after cardiac surgery.

PMID- 29451340
TI  - Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying
      Therapeutic Efficacies.
AB  - Stem cells are emerging as promising treatment strategies for several brain
      disorders and pathologies. In this study, we explored the potential of creating
      induced pluripotent stem cell-derived neural stem cells (ipNSC) by using either
      unmodified or gene-modified somatic cells and tested their fate and therapeutic
      efficacies in vitro and in vivo. We show that cells engineered in somatic state
      lose transgene-expression during the neural induction process, which is partially
      restored by histone deacetylase inhibitor treatment whereas cells engineered at
      the ipNSC state have sustained expression of transgenes. In vivo, bimodal mouse
      and human ipNSCs engineered to express tumor specific death-receptor ligand and
      suicide-inducing therapeutic proteins have profound anti-tumor efficacy when
      encapsulated in synthetic extracellular matrix and transplanted in mouse models
      of resected-glioblastoma. This study provides insights into using somatic cells
      for treating CNS disorders and presents a receptor-targeted cancer therapeutic
      approach for brain tumors. Stem Cells 2018;36:932-942.

PMID- 29451342
TI  - Deleterious Effect of Anti-Angiotensin II Type 1 Receptor Antibodies Detected
      Pretransplant on Kidney Graft Outcomes is Both Proper and Synergistic WITH DONOR
      SPECIFIC ANTI-HLA ANTIBODIES.
AB  - AIM: Both donor-specific antibodies (DSA) and anti-angiotensin II type 1 receptor
      antibodies (AT1R-abs) have been associated with poor graft outcomes after kidney
      transplantation (KT). We aimed to understand the impact of pretransplant AT1R-abs
      with or without concomitant DSA on KT outcomes. METHODS: Seventy-six patients
      transplanted in 2009 were studied. DSA (MFI>1000) and/or AT1R-abs (>10UI) were
      detected by solid-phase assays in pre-KT sera. Multivariable Cox regression
      models were used to determine independent predictors of outcomes: acute rejection
      (AR) and graft failure. RESULTS: At transplant, 48 patients were AT1R-abs (-)/DSA
      (-), 12 AT1R-abs (+)/DSA (-), 9 AT1R-abs (-)/DSA (+) and 7 AT1R-abs (+)/DSA (+).
      Incidence of acute rejection at 1-year increased from 6% in AT1R-abs (-)/DSA (-),
      to 35% in AT1R-abs (+)/DSA (-), 47% in AT1R-abs (-)/DSA (+) and 43% in AT1R-abs
      (+)/DSA (+) (P<0.001). No difference in DSA strength and C1q-binding ability was
      observed between AT1R-abs (-) /DSA (+) and AT1R-abs (+)/DSA (+) patients. Graft
      survival at 6-years was the lowest in AT1R-abs (+)/DSA (+) (57%), followed by
      AT1R-abs (+)/DSA (-) (67%), and higher in AT1R-abs (-)/DSA (-) (94%) and AT1R-abs
      (-)/DSA (+) (89%) patients (P=0.012). AT1R-abs (+)/DSA (-) (HR=6.41, 95% CI: 1.43
      28.68; P=0.015) and AT1R-abs (+)/DSA (+) (HR=7.75, 95% CI: 1.56-38.46; P=0.012)
      were independent predictors of graft failure. CONCLUSIONS: AR incidence and graft
      failure were associated with both DSA and AT1R-abs. These results demonstrate a
      proper negative effect of AT1R-abs on graft outcomes, besides a synergistic one
      with DSA. Pretransplant AT1R-abs should be acknowledge to better stratify
      patients' immunological risk.

PMID- 29451343
TI  - Molecular Tectonics with Di- and Trinuclear Organotin Compounds.
AB  - Di- and trinuclear organotin(IV) complexes, in which the metal atoms are
      separated by large aromatic connectors, are useful building blocks for self
      assembly. This is demonstrated by the preparation of [1+1], [2+2], and [2+3]
      macrocyclic and cage-type structures in combination with organic aromatic
      dicarboxylates. The linkage of the metal atoms by organic binders and the option
      of varying the number of reactive M-X sites generate versatile building blocks
      enabling molecular tectonics instead of the node-based strategy generally
      employed in metallo-supramolecular self-assembly.

PMID- 29451345
TI  - Unsymmetrical, Cyclic Diborenes and Thermal Rearrangement to a Borylborylene.
AB  - Cyclic diboranes(4) based on a chelating monoanionic benzylphosphine linker were
      prepared through boron-silicon exchange between arylsilanes and B2 Br4 .
      Coordination of Lewis bases to the remaining sp2 boron atom yielded unsymmetrical
      sp3 -sp3 diboranes, which were reduced with KC8 to their corresponding trans
      diborenes. These compounds were studied with a combination of spectroscopic
      methods, X-ray diffraction, and DFT calculations. PMe3 -stabilized diborene 6 was
      found to undergo thermal rearrangement to gem-diborene 8. DFT calculations on 8
      reveal a polar boron-boron bond, and indicate that the compound is best described
      as a borylborylene.

PMID- 29451344
TI  - A case of microscopic, multiple sclerosing pneumocytoma.
AB  - Sclerosing pneumocytoma is a rare tumor of the lung, commonly affecting middle
      aged women, and is mostly isolated. Although this tumor is thought to be derived
      from primitive respiratory epithelial cells, the characteristics of the precursor
      cells are still unknown. A 19-year-old woman presented with multiple nodules in
      the right lung. Partial resection of the right middle lobe was performed, and
      seven sclerosing pneumocytomas, including four that were microscopic, were
      detected. The latter showed a simple papillary pattern, and three of them
      consisted of only round cell-like cells (single population). Interestingly, these
      round cell-like cells were positive for both p63 and TTF-1, but totally negative
      for SP-A. On the other hand, the tumor cells of the other four sclerosing
      pneumocytomas showing a papillary pattern with a dual population, were diffusely
      positive for TTF-1 and focally positive for SP-A (only in surface cells), but
      negative or very focally positive for p63. It has been reported that p63-positive
      stem cell-like cells are present in the distal airway and have potential to
      differentiate into type II pneumocytes. The immunohistochemical features of these
      multiple microscopic lesions suggest that the p63-TTF-1 double-positive cells are
      candidate precursor cells of sclerosing pneumocytoma.

PMID- 29451346
TI  - Helicenophyrins: Expanded Carbaporphyrins Incorporating Aza[5]helicene and
      Heptacyclic S-Shaped Aza[5]helicene Motifs.
AB  - Incorporation of phenanthrene into a hexaphyrin(1.1.1.1.1.0) frame resulted in
      intramolecular ring fusion, thus giving rise to chiral helicenophyrins. These
      molecules contain helicene and porphyrin features by incorporating either an
      aza[5]helicene or heptacyclic S-shaped aza[5]helicene.

PMID- 29451347
TI  - A rare case of ectopic papillary thyroid carcinoma transformed into squamous cell
      carcinoma.
AB  - A rare case of a metastatic ectopic papillary thyroid carcinoma (PTC) of the lung
      that transformed into a squamous cell carcinoma (SCC) that resembles pulmonary
      SCC is reported. A subcutaneous ectopic PTC in the left anterior neck area,
      together with a normal thyroid gland, were excised. The ectopic PTC showed
      thyroglobulin, TTF-1 and PAX-8 immunoreactivity and a BRAF V600E mutation. During
      the post-operative follow-up period, a rapidly growing 2 cm nodular lesion in the
      lower left lobe of the lung was detected. The lung tumor consisted of solid
      sheets and nests of squamous cells but without the nuclear features of PTC.
      Neither papillary nor follicular structures of cancer cells were identified.
      Carcinoma cells were positive for TTF-1, PAX-8, p40, CK14, and p63, while showing
      a high Ki-67 labeling index and a BRAF V600E mutation. These results support our
      interpretation of a PTC that originated from ectopic thyroid tissue in the left
      anterior neck and that developed a lung metastasis showing squamous cell
      differentiation.

PMID- 29451348
TI  - Sigmatropic Rearrangements of Hypervalent-Iodine-Tethered Intermediates for the
      Synthesis of Biaryls.
AB  - Metal-free dehydrogenative couplings of aryliodanes with phenols to afford 2
      hydroxy-2'-iodobiaryls have been developed. This reaction proceeds through ligand
      exchange on the hypervalent iodine atom followed by a [3,3] sigmatropic
      rearrangement and with complete regioselectivity. This coupling, in combination
      with in situ oxidation by mCPBA, enables the convenient conversion of iodoarenes
      into desirable biaryls. The obtained biaryls have convertible iodo and hydroxy
      groups in close proximity, and are thus synthetically useful, as exemplified by
      the controlled syntheses of pi-extended furans and a substituted [5]helicene. DFT
      calculations clearly revealed that the rearrangement is sigmatropic, with C-C
      bond formation and I-O bond cleavage proceeding in a concerted manner. Acetic
      acid, which was found to be the best solvent for this protocol, renders the
      iodine atom more cationic and thus accelerates the sigmatropic rearrangement.

PMID- 29451349
TI  - Reply.

PMID- 29451350
TI  - An economic assessment of contemporary kidney transplant practice.
AB  - Kidney transplantation is the optimal therapy for end-stage renal disease,
      prolonging survival and reducing spending. Prior economic analyses of kidney
      transplantation, using Markov models, have generally assumed compatible, low-risk
      donors. The economic implications of transplantation with high Kidney Donor
      Profile Index (KDPI) deceased donors, ABO incompatible living donors, and HLA
      incompatible living donors have not been assessed. The costs of transplantation
      and dialysis were compared with the use of discrete event simulation over a 10
      year period, with data from the United States Renal Data System, University
      HealthSystem Consortium, and literature review. Graft failure rates and
      expenditures were adjusted for donor characteristics. All transplantation options
      were associated with improved survival compared with dialysis (transplantation:
      5.20-6.34 quality-adjusted life-years [QALYs] vs dialysis: 4.03 QALYs). Living
      donor and low-KDPI deceased donor transplantations were cost-saving compared with
      dialysis, while transplantations using high-KDPI deceased donor, ABO-incompatible
      or HLA-incompatible living donors were cost-effective (<$100 000 per QALY).
      Predicted costs per QALY range from $39 939 for HLA-compatible living donor
      transplantation to $80 486 for HLA-incompatible donors compared with $72 476 for
      dialysis. In conclusion, kidney transplantation is cost-effective across all
      donor types despite higher costs for marginal organs and innovative living donor
      practices.

PMID- 29451352
TI  - Chronic exposure of mice to low doses of imazalil induces hepatotoxicity at the
      physiological, biochemical, and transcriptomic levels.
AB  - Imazalil (IMZ), which is a widely used fungicide, can accumulate in the body and
      threaten an animal's health. However, this fungicide has adverse effects on
      aquatic organisms and ultimately affects human health when it leaches into the
      environment. Our research tried to determine that if IMZ might cause liver damage
      and its potential to cause-related diseases. In this study, male adult C57BL/6
      mice were exposed to 0.1, 0.5, or 2.5 mg/kg body weight IMZ in drinking water for
      15 weeks. Then, we evaluated the liver damage at the physiological, biochemical,
      and transcriptome levels in mice after chronic IMZ exposure. We observed serious
      ballooning degeneration of hepatocytes in the IMZ-treated groups. And IMZ induced
      oxidative stress and caused the disorders of bile acid metabolism in mice. In
      addition, the transcriptome data showed that IMZ has substantial influence on
      several pathways, including metabolic pathways for drug metabolism, RNA
      transport, and bile secretion. We further confirmed that the mRNA expression of
      the key genes involved in oxidative stress and bile acid metabolism were changed
      of mice exposed to IMZ. Our data suggested that chronic IMZ exposure could induce
      hepatotoxicity in mice at the physiological, biochemical, and transcriptome
      levels.

PMID- 29451351
TI  - Delphinidin induces apoptosis and inhibits epithelial-to-mesenchymal transition
      via the ERK/p38 MAPK-signaling pathway in human osteosarcoma cell lines.
AB  - Delphinidin is major anthocyanidin that is extracted from many pigmented fruits
      and vegetables. This substance has anti-oxidant, anti-inflammatory, anti
      angiogenic, and anti-cancer properties. In addition, delphinidin strongly
      suppresses the migration and invasion of various cancer cells during
      tumorigenesis. Although delphinidin has anti-cancer effects, little is known
      about its functional roles in osteosarcoma (OS). For these reasons, we have
      demonstrated the effects of delphinidin on OS cell lines. The effects of
      delphinidin on cell viability and growth of OS cells were assessed using the MTT
      assay and colony formation assays. Hoechst staining indicated that the
      delphinidin-treated OS cells were undergoing apoptosis. Flow cytometry, confocal
      microscopy, and a western blot analysis also indicated evidence of apoptosis.
      Inhibition of cell migration and invasion was found to be associated with
      epithelial-to-mesenchymal transition (EMT), observed by using a wound healing
      assay, an invasion assay, and a western blot analysis. Furthermore, delphinidin
      treatment resulted in a profound reduction of phosphorylated forms of ERK and
      p38. These findings demonstrate that delphinidin treatment suppressed EMT through
      the mitogen-activated protein kinase (MAPK) signaling pathway in OS cell lines.
      Taken together, our results suggest that delphinidin strongly inhibits cell
      proliferation and induces apoptosis. Delphinidin treatment also suppresses cell
      migration and prevents EMT via the MAPK-signaling pathway in OS cell lines. For
      these reasons, delphinidin has anti-cancer effects and can suppress metastasis in
      OS cell lines, and it might be worth using as an OS therapeutic agent.

PMID- 29451353
TI  - In vitro cytotoxicity assessment of nanodiamond particles and their osteogenic
      potential.
AB  - Scaffolds functionalized with nanodiamond particles (nDP) hold great promise with
      regard to bone tissue formation in animal models. Degradation of the scaffolds
      over time may leave nDP within the tissues, raising concerns about possible long
      term unwanted effects. Human SaOS-2 osteoblast-like cells and U937 monoblastoid
      cells were exposed to five different concentrations (0.002-2 mg/L) of nDP (size
      range: 2.36-4.42 nm) for 24 h. Cell viability was assessed by impedance-based
      methods. The differential expression of stress and toxicity-related genes was
      evaluated by polymerase chain reaction (PCR) super-array, while the expression of
      selected inflammatory and cell death markers was determined by reverse
      transcriptase quantitative polymerase chain reaction (RT-qPCR). Furthermore, the
      expression of osteogenic genes by SaOS-2 cells, alkaline phosphatase activity and
      the extracellular calcium nodule deposition in response to nDP were determined in
      vitro. Cells responded differently to higher nDP concentrations (>=0.02 mg/L),
      that is, no loss of viability for SaOS-2 cells and significantly reduced
      viability for U937 cells. Gene expression showed significant upregulation of
      several cell death and inflammatory markers, among other toxicity reporter genes,
      indicating inflammatory and cytotoxic responses in U937 cells. Nanodiamond
      particles improved the osteogenicity of osteoblast-like cells with no evident
      cytotoxicity. However, concentration-dependent cytotoxic and inflammatory
      responses were seen in the U937 cells, negatively affecting osteogenicity in co
      cultures. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1697
      1707, 2018.

PMID- 29451354
TI  - Are we underestimating the quality of aviremic hepatitis C-positive kidneys? Time
      to reconsider.
AB  - Kidney Donor Risk Index (KDRI) introduced in 2009 included hepatitis C serologic
      but not viremic status of the donors. With nucleic acid amplification testing
      (NAT) now being mandatory, further evaluation of these donors is possible. We
      conducted a retrospective matched case-control analysis of adult deceased donor
      kidney transplants performed between December 5, 2014 to December 31, 2016 with
      the KDRI score and hepatitis C virus antibody (HCV Ab) and NAT testing status
      obtained from the United Network for Organ Sharing database. The 205 aviremic HCV
      Ab+ NAT - kidney transplants were compared to KDRI matched control kidneys that
      were HCV Ab-NAT-. The aviremic HCV kidneys were recovered from donors who were
      significantly younger, more likely to be white, and less likely to have
      hypertension and diabetes. The majority of the recipients of the aviremic HCV
      kidneys when compared to matched controls were HCV positive: 90.2% vs 4.3%. The
      recipients were significantly older, were on dialysis for a shorter time, and
      were transplanted sooner. The graft survival of aviremic HCV kidneys was similar
      (P < .08). If the HCV status of the aviremic kidneys was assumed to be negative,
      122 more kidneys could have been allocated to patients with estimated
      posttransplant survival <20. Seven kidneys would no longer have Kidney Donor
      Profile Index >85%. Further policies might consider these findings to
      appropriately allocate these kidneys.

PMID- 29451355
TI  - A Critical Evaluation of In Vitro Hesperidin 2S Bioavailability in a Model
      Combining Luminal (Microbial) Digestion and Caco-2 Cell Absorption in Comparison
      to a Randomized Controlled Human Trial.
AB  - SCOPE: Bioavailability strongly determines polyphenol bioactivity, and is
      strongly influenced by food matrix, enzymatic and microbial degradation, and
      gastrointestinal absorption. To avoid human trials for pre-screening of
      polyphenol bioavailability, studies have focused on in vitro model development.
      Nevertheless, their predictive value for bioavailability can be questioned.
      METHOD AND RESULTS: We used the orange flavonoid hesperidin 2S to validate a
      model combining digestion in the simulator of the human intestinal microbial
      ecosystem (SHIME) and Caco-2 cell transport, with a human intervention study. In
      vitro, hesperidin was resistant to degradation in the stomach and small
      intestine, but was rapidly deconjugated on reaching the proximal colon. Extensive
      and colon-region-specific degradation to smaller phenolics was observed.
      Hydrocaffeic and dihydroisoferulic acid accumulated in proximal, and hydroferulic
      acid in distal colon. Caco-2 transport was the highest for dihydroisoferulic
      acid. In humans, plasma and urine hesperetin-glucuronide levels increased
      significantly, whereas the impact on small phenolics was limited. CONCLUSIONS: In
      the combined in vitro model, smaller phenolics strongly accumulated, whereas in
      humans, hesperetin conjugates were the main bioavailable compounds. Future in
      vitro model development should focus on simulating faster polyphenol absorption
      and elimination of smaller phenolics to improve their predictive value of in vivo
      polyphenol bioavailability.

PMID- 29451356
TI  - Disinfection of saline solutions and devices for nasal irrigation: Why, when and
      how?

PMID- 29451357
TI  - Assessing normal values for the FACE-Q rhinoplasty module: An observational
      study.
AB  - OBJECTIVES: The goal of this study was to determine normal values for the FACE-Q
      rhinoplasty module. DESIGN: A prospective monocentric observational cohort study.
      SETTING: We tested FACE-Q Satisfaction with Nose and Satisfaction with Nostrils
      in two groups of patients, seeking or not a rhinoplasty. PARTICIPANTS: One
      hundred and four patients were included in the study, fifty-two in each group.
      MAIN OUTCOME MEASUREMENTS: Primary outcome was to identify possible cutting
      scores to establish normal values for each of the FQRM questionnaires. RESULTS:
      Regarding the Satisfaction with Nose scale, there was a statistically significant
      difference between the two groups (P < .001). Area under the ROC curve was 0.964
      (95% CI = 0.931-0.997). Forty-seven points was the value presenting the best
      Youden index (sensitivity = 96.2%, specificity = 86.5%). Regarding the
      Satisfaction with Nostrils scale, there was a statistically significant
      difference between the two groups (P < .001). Area under the ROC curve was 0.820
      (95% CI = 0.741-0.899). Sixty-four points was the value presenting the best
      Youden index (sensitivity = 94.2%, specificity = 53.8%). CONCLUSION: This is the
      first study to generate normative data for the FACE-Q rhinoplasty module. The
      findings presented here have important implications for future clinical care and
      research. The definition of a normal score can help practitioners to better
      analyse their patients and to support a therapeutic indication.

PMID- 29451359
TI  - Assessment of narrative writing by Persian-speaking students with hearing
      impairments.
AB  - OBJECTIVE: Previous studies have highlighted that narrative skill is critical to
      the development of the literacy skills by children. Children with cochlear
      implants (CI) and hearing aids (HA) may have problems in narrative development
      compared to peers with healthy hearing (HH). There is no exact data about the
      narrative writing ability of Persian-speaking students who are hearing-impaired.
      This study was undertaken to compare the microstructure and macrostructure scores
      for narrative writing of Persian-speaking students who are hearing-impaired and
      peers with HH. DESIGN: This was a cross-sectional descriptive-analytical study.
      SETTING: The subjects were recruited from elementary schools in the city of
      Tehran. PARTICIPANTS: A total of 144 elementary school students were
      participated. OUTCOME MEASURES: The written narratives were elicited using a
      wordless pictorial storybook story. Three-way ANOVA with post hoc adjusted
      Bonferroni test was applied to determine the main effects and interactions of
      grounded variables on the microstructure and macrostructure components of
      narrative writing. RESULTS: No significant differences were observed in the
      macrostructure components of narrative writing between hearing-impaired and HH
      students. Factors analysis showed that the 4th grade HH students had
      significantly the highest scores, and the 3rd grade HA students had significantly
      the lowest scores in microstructure components of narrative writing. CONCLUSION:
      The findings revealed that hearing-impaired students similarly to their HH peers
      can transmit the main idea (macrostructure) of narrative writing, but show
      critical difficulties when using complete grammatical elements (microstructures)
      to form sentences to convey the idea in the narrative.

PMID- 29451358
TI  - Electronic Structure Characterization of Cross-Linked Sulfur Polymers.
AB  - Cross-linked polymers of elemental sulfur are of potential interest for
      electronic applications as they enable facile thin-film processing of an abundant
      and inexpensive starting material. Here, we characterize the electronic structure
      of a cross-linked sulfur/diisopropenyl benzene (DIB) polymer by a combination of
      soft and hard X-ray photoelectron spectroscopy (SOXPES and HAXPES). Two different
      approaches for enhancing the conductivity of the polymer are compared: the
      addition of selenium in the polymer synthesis and the addition of lithium
      bis(trifluoromethanesulfonyl)imide (LiTFSI) during film preparation. For the
      former, we observe the incorporation of Se into the polymer structure resulting
      in a changed valence-band structure. For the latter, a Fermi level shift in
      agreement with p-type doping of the polymer is observed and also the formation of
      a surface layer consisting mostly of TFSI anions.

PMID- 29451360
TI  - Defining Optimal Surgical Treatment for Recurrent Hepatocellular Carcinoma: A
      Propensity Score Matched Analysis.
AB  - Salvage liver transplantation (sLT) and repeated resection (RR) are effective
      treatments for recurrent hepatocellular carcinoma (HCC), and comparisons of the
      oncological outcomes between these 2 modalities were scarce. Consecutive patients
      admitted for either sLT or RR for recurrent HCC were recruited. All patients in
      the present series received either prior hepatectomy, ablative therapy, or both
      before RR or sLT. Patient demographic, perioperative, and outcome data were
      analyzed. A survival analysis was performed after propensity score matching.
      There were 277 eligible patients recruited, and 67 and 210 of them underwent sLT
      and RR, respectively. Significant differences in preoperative hemoglobin,
      albumin, Model of End-Stage Liver Disease (MELD) score, and tumor number were
      found between the sLT and RR groups. After 1:3 propensity score matching, there
      were 36 sLT and 108 RR patients for comparison. The median age, MELD, alpha
      fetoprotein, and tumor size and number of the matched population were 57 years,
      7.5, 16 ng/mL, 2.5 cm, and 1, respectively. There was no difference in the
      hospital mortality and complication rate (Clavien IIIa or above) between the
      groups. The recurrence rate after RR was significantly higher than for the
      patients who received sLT (72.2% versus 27.8%; P < 0.001). Following RR, 3
      patients received liver transplantation for further recurrence, and 54.6% of the
      patients developed nontransplantable recurrence. The 5-year disease-free survival
      (DFS) and overall survival (OS) were both superior in the sLT group (DFS, 71.6%
      versus 32.8%, P < 0.001; OS, 72.8% versus 48.3%, P = 0.007). In conclusion, sLT
      is superior to RR for treatment of recurrent HCC in terms of DFS and OS. The high
      rate of nontransplantable recurrence after reresection underscores the importance
      of timely sLT.

PMID- 29451361
TI  - Development of a Focused Library of Triazole-Linked Privileged-Structure-Based
      Conjugates Leading to the Discovery of Novel Phenotypic Hits against Protozoan
      Parasitic Infections.
AB  - Protozoan infections caused by Plasmodium, Leishmania, and Trypanosoma spp.
      contribute significantly to the burden of infectious diseases worldwide, causing
      severe morbidity and mortality. The inadequacy of available treatments calls for
      cost- and time-effective drug discovery endeavors. To this end, we envisaged the
      triazole linkage of privileged structures as an effective drug design strategy to
      generate a focused library of high-quality compounds. The versatility of this
      approach was combined with the feasibility of a phenotypic assay, integrated with
      early ADME-tox profiling. Thus, an 18-membered library was efficiently assembled
      via Huisgen cycloaddition of phenothiazine, biphenyl, and phenylpiperazine
      scaffolds. The resulting 18 compounds were then tested against seven parasite
      strains, and counter-screened for selectivity against two mammalian cell lines.
      In parallel, hERG and cytochrome P450 (CYP) inhibition, and mitochondrial
      toxicity were assessed. Remarkably, 10-((1-(3-([1,1'-biphenyl]-3-yloxy)propyl)-1H
      1,2,3-triazol-5-yl)methyl)-10H-phenothiazine (7) and 10-(3-(1-(3-([1,1'-biphenyl]
      3-yloxy)propyl)-1H-1,2,3-triazol-4-yl)propyl)-10H-phenothiazine (12) showed
      respective IC50 values of 1.8 and 1.9 MUg mL-1 against T. cruzi, together with
      optimal selectivity. In particular, compound 7 showed a promising ADME-tox
      profile. Thus, hit 7 might be progressed as an antichagasic lead.

PMID- 29451362
TI  - Simultaneous Multiple MS Binding Assays for the Dopamine, Norepinephrine, and
      Serotonin Transporters.
AB  - In this work, we present label-free, mass-spectrometry-based binding assays (MS
      Binding Assays), targeting the human dopamine, norepinephrine, and serotonin
      transporters (hDAT, hNET, and hSERT) in simultaneous binding experiments. Using a
      validated LC-ESI-MS/MS method for quantification of the selective dopamine
      transporter inhibitor (R,R)-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin
      3-ol ((R,R)-D-84), the selective norepinephrine transporter inhibitor (S,S)
      reboxetine, and the selective serotonin reuptake inhibitor (S)-citalopram,
      binding affinities at the three monoamine transporters could be characterized
      simultaneously in a single binding experiment. The performed simultaneous
      saturation and competition experiments yielded results that are in good
      accordance with those determined in MS Binding Assays addressing the monoamine
      transporters individually. The results obtained from this study underscore the
      potential of MS Binding Assays for simultaneous affinity determination at
      different targets, which is difficult to accomplish with conventional radioligand
      binding assays.

PMID- 29451363
TI  - The genome of the marine medaka Oryzias melastigma.
AB  - Marine medaka (Oryzias melastigma) is considered to be a useful fish model for
      marine and estuarine ecotoxicology studies and has good potential for field-based
      population genomics because of its geographical distribution in Asian estuarine
      and coastal areas. In this study, we present the first whole-genome draft of O.
      melastigma. The genome assembly consists of 8,602 scaffolds (N50 = 23.737 Mb) and
      a total genome length of 779.4 Mb. A total of 23,528 genes were predicted, and
      12,670 gene families shared with three teleost species (Japanese medaka, mangrove
      killifish and zebrafish) were identified. Genome analyses revealed that the O.
      melastigma genome is highly heterozygous and contains a large number of repeat
      sequences. This assembly represents a useful genomic resource for fish
      scientists.

PMID- 29451364
TI  - Prevalence of celiac disease in adult Chinese patients with diarrhea-predominant
      irritable bowel syndrome: A prospective, controlled, cohort study.
AB  - OBJECTIVE: Celiac disease is a chronic inflammatory enteropathy with a symptom
      spectrum similar to that of irritable bowel syndrome (IBS). It is a common but
      largely undiagnosed condition in the Western countries. However, it is extremely
      rare among Chinese individuals, and few studies have investigated its prevalence
      in China. The aim was to determine the prevalence of celiac disease in patients
      with IBS who were diagnosed using the Rome III criteria in a single center of
      northern China. METHODS: This was a single-center, prospective, controlled cohort
      study performed in Qilu Hospital involving 246 patients with IBS and 246 healthy
      controls. Blood samples were drawn to assess serum tissue transglutaminase
      immunoglobulin A (tTg-IgA). Patients with a positive or equivocal tTg-IgA (>=15
      U/mL) were subjected to probe-based confocal laser endomicroscopy (pCLE) and
      duodenal biopsy to confirm celiac disease. RESULTS: Altogether 12 (4.9%) patients
      with IBS and two (0.8%) healthy controls were positive or equivocal for serum tTg
      IgA. Of these, five patients with IBS underwent pCLE and a targeted biopsy; all
      were histopathologically found to have celiac disease, although one was
      eventually diagnosed with lymphoma. After implementation of a gluten-free diet,
      seven patients serologically positive for IBS showed clinical improvement, thus
      our study illustrated a minimum prevalence of 2.85% of celiac disease among
      patients with IBS in our center. CONCLUSIONS: Celiac disease is not rare in
      Chinese individuals, particularly among those with IBS. Therefore, it should
      receive higher attention in clinical practice in China.

PMID- 29451365
TI  - The genome of the freshwater monogonont rotifer Brachionus calyciflorus.
AB  - Monogononta is the most speciose class of rotifers, with more than 2,000 species.
      The monogonont genus Brachionus is widely distributed at a global scale, and a
      few of its species are commonly used as ecological and evolutionary models to
      address questions related to aquatic ecology, cryptic speciation, evolutionary
      ecology, the evolution of sex and ecotoxicology. With the importance of
      Brachionus species in many areas of research, it is remarkable that the genome
      has not been characterized. This study aims to address this lacuna by presenting,
      for the first time, the whole-genome assembly of the freshwater species
      Brachionus calyciflorus. The total length of the assembled genome was 129.6 Mb,
      with 1,041 scaffolds. The N50 value was 786.6 kb, and the GC content was 24%. A
      total of 16,114 genes were annotated with repeat sequences, accounting for 21% of
      the assembled genome. This assembled genome may form a basis for future studies
      addressing key questions on the evolution of monogonont rotifers. It will also
      provide the necessary molecular resources to mechanistically investigate
      ecophysiological and ecotoxicological responses.

PMID- 29451366
TI  - Near-infrared bone densitometry: A feasibility study on distal radius
      measurement.
AB  - Osteoporosis, defined as decreased bone mineral density (BMD), poses patients in
      dangers for fracture risk and has become a major public health problem worldwide
      because of is associated morbidity, mortality and costs. Without doubt, early
      detection and timely intervention are important to successfully manage
      osteoporosis and its associated complications. The dual-energy x-ray
      absorptiometry (DXA) is the most popular and standard method to measure BMD.
      However, limitations including radiation exposure and availability restrict its
      application for osteoporosis screening among general population. In this study,
      we developed a simple method to detect human distal radius bone density based on
      near infrared (NIR) image system. Among 10 volunteers (including 5 young and 5
      elderly participants) receiving bone density measurement using our NIR image
      system at the ultradistal part of bilateral distal radius, we demonstrated a
      strong correlation between the optical attenuation and BMD measured with DXA,
      which may facilitate predicting bone density status. We hope our potential NIR
      image system may open a new avenue for development of osteoporosis screening
      facilities and help in prevention of osteoporosis related fracture and its
      associated complications in the near future. Pearson's correlations between BMD
      values from the DXA and light intensity of NIR system.

PMID- 29451367
TI  - Association between famine exposure in early life and type 2 diabetes mellitus
      and hyperglycemia in adulthood: Results from the China Health And Retirement
      Longitudinal Study (CHARLS).
AB  - BACKGROUND: Studies have revealed the association between famine in early life
      and type 2 diabetes mellitus (T2DM) in adulthood. However, studies on the Great
      Chinese Famine were not conducted nationwide. Because of regional variations in
      the severity of this famine, the results of regional studies are limited. This
      study explored associations between famine and T2DM in adulthood in a nationwide
      study. METHODS: The present study was performed on 7262 participants who were
      born between 1 October 1949 and 1 July 1966 using baseline data collected for the
      China Health And Retirement Longitudinal Study (CHARLS) in 2011. Participants
      were divided according to birthdate into cohorts with fetal, late, middle, and
      early childhood exposure and no exposure to famine. Logistic regression models
      were used to analyze the association between famine exposure in early life and
      the risk of T2DM and hyperglycemia in adulthood. RESULTS: For females, the risk
      of hyperglycemia was higher for famine-exposed than not exposed cohort (odds
      ratios [OR] 1.34 and 95% confidence intervals [CIs]: 1.34 [1.04-1.74], 1.48 [1.15
      1.90], 1.38 [1.06-1.79], and 1.57 [1.25-1.98] for fetal, early, middle, and late
      childhood exposure, respectively), and this association was even stronger in
      female participants who lived in rural areas before the age of 16 years. In
      males, the risk of T2DM was lower for the early and late childhood exposure than
      no exposure cohorts (OR [95% CIs]: 0.65 [0.49-0.86] and 0.74 [0.56-0.98],
      respectively). [Correction added on 23 July 2018, after first online publication:
      Parts of the above 'Results' section have been corrected to interchange the
      citation of the words 'late' and 'early'.] CONCLUSION: Exposure to famine during
      early life can increase the risk of hyperglycemia in female adults, but may
      decrease the risk of T2DM in males.

PMID- 29451368
TI  - Public health response to an imported case of canine melioidosis.
AB  - Melioidosis in humans presents variably as fulminant sepsis, pneumonia, skin
      infection and solid organ abscesses. It is caused by Burkholderia pseudomallei,
      which in the United States is classified as a select agent, with "potential to
      pose a severe threat to both human and animal health, to plant health or to
      animal and plant products" (Federal Select Agent Program,
      http://www.selectagents.gov/, accessed 22 September 2016). Burkholderia
      pseudomallei is found in soil and surface water in the tropics, especially South
      East Asia and northern Australia, where melioidosis is endemic. Human cases are
      rare in the United States and are usually associated with travel to endemic
      areas. Burkholderia pseudomallei can also infect animals. We describe a
      multijurisdictional public health response to a case of subclinical urinary B.
      pseudomallei infection in a dog that had been adopted into upstate New York from
      a shelter in Thailand. Investigation disclosed three human contacts with single,
      low-risk exposures to the dog's urine at his residence, and 16 human contacts
      with possible exposure to his urine or culture isolates at a veterinary hospital.
      Contacts were offered various combinations of symptom/fever monitoring, baseline
      and repeat B. pseudomallei serologic testing, and antibiotic post-exposure
      prophylaxis, depending on the nature of their exposure and their personal medical
      histories. The dog's owner accepted recommendations from public health
      authorities and veterinary clinicians for humane euthanasia. A number of animal
      rescue organizations actively facilitate adoptions into the United States of
      shelter dogs from South-East Asia. This may result in importation of B.
      pseudomallei into almost any community, with implications for human and animal
      health.

PMID- 29451369
TI  - Discovery of Rogaratinib (BAY 1163877): a pan-FGFR Inhibitor.
AB  - Rogaratinib (BAY 1163877) is a highly potent and selective small-molecule pan
      fibroblast growth factor receptor (FGFR) inhibitor (FGFR1-4) for oral application
      currently being investigated in phase 1 clinical trials for the treatment of
      cancer. In this publication, we report its discovery by de novo structure-based
      design and medicinal chemistry optimization together with its pharmacokinetic
      profile.

PMID- 29451370
TI  - Three novel HLA alleles discovered in Koreans, HLA-A*26:118, DQB1*02:65 and
      DPB1*05:01:07.
AB  - Three novel HLA alleles, HLA-A*26:118, DQB1*02:65 and DPB1*05:01:07, were
      identified and confirmed by monoallelic sequencing.

PMID- 29451371
TI  - Young's Modulus and Load Complexity: Modeling Their Effects on Proximal Femur
      Strain.
AB  - Finite element analysis (FEA) is a powerful tool for evaluating questions of
      functional morphology, but the application of FEA to extant or extinct creatures
      is a non-trivial task. Three categories of input data are needed to appropriately
      implement FEA: geometry, material properties, and boundary conditions. Geometric
      data are relatively easily obtained from imaging techniques, but often material
      properties and boundary conditions must be estimated. Here we conduct sensitivity
      analyses of the effect of the choice of Young's Modulus for elements representing
      trabecular bone and muscle loading complexity on the proximal femur using a
      finite element mesh of a modern human femur. We found that finite element meshes
      that used a Young's Modulus between 500 and 1,500 MPa best matched experimental
      strains. Loading scenarios that approximated the insertion sites of hip
      musculature produced strain patterns in the region of the greater trochanter that
      were different from scenarios that grouped muscle forces to the superior greater
      trochanter, with changes in strain values of 40% or more for 20% of elements. The
      femoral head, neck, and proximal shaft were less affected (e.g. approximately 50%
      of elements changed by 10% or less) by changes in the location of application of
      muscle forces. From our sensitivity analysis, we recommend the use of a Young's
      Modulus for the trabecular elements of 1,000 MPa for the proximal femur (range
      500-1,500 MPa) and that the muscular loading complexity be dependent on whether
      or not strains in the greater trochanter are the focus of the analytical
      question. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29451372
TI  - Morphological Spectra of Adult Human Stellate Ganglia: Implications for Thoracic
      Sympathetic Denervation.
AB  - Cardiac sympathetic denervation (CSD) to treat ventricular arrhythmias (VAs)
      requires transection at the middle or lower third of stellate (cervicothoracic)
      ganglia (SG). However, the morphological appearance of the adult SG and
      distribution of neuronal somata within it are not well described. To determine
      the morphology of left and right SG (LSG and RSG) and the distribution of somata
      within. LSG and RSG (n = 28) from 14 embalmed adult cadavers were dissected
      intact. Weight, volume, height, morphologic appearance, relationship between C8
      and T1 ganglia (which form the SG) were determined, along with histology.
      Demographics, history of cardiac disease, and cause of death were also reviewed.
      Mean age of the subjects was 76 +/- 13 years, and 5/14 were male. Three distinct
      morphologies of SG were identified: fusiform-rounded; fusiform-elongated; and
      bilobed. RSG and LSG did not differ in weight or volume. RSG were longer than LSG
      (2.05 +/- 0.28 cm vs. 1.66 +/- 0.47 cm, P = 0.024). Bilobed morphology was most
      common in RSGs (8/14), while fused, elongated was most common in LSG (8/14). RSGs
      lacked fused, rounded appearance, while 28.6% of LSG appeared as such.
      Histologically, one focus of somata was seen in fused rounded ganglia, while
      fused elongated SG had somata distributed throughout. Bilobed SG demonstrated two
      foci of somata, with the interconnecting stalk containing sparse somata. SG
      appears in three major forms and contains varying distributions of somata. Larger
      studies are warranted to define the relationship between gross anatomy and
      distribution of neuronal somata to improve the efficacy of CSD in treating VAs.
      Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29451373
TI  - Regional Structural and Functional Specializations in the Urethra of the Female
      Rat: Evidence for Complex Physiological Control Systems.
AB  - This study characterizes the complex structural and functional elements of the
      female rat urethra that may be involved in controlling urethral closure and
      continence. Urethras were dissected from female Sprague-Dawley rats (N = 12)
      euthanized by pentobarbital overdose. Tissues were fixed (4% paraformaldehyde),
      frozen, and sectioned (8 MUm) for light microscopy and immunohistochemistry.
      Antibodies were used to detect immunoreactivity to calcitonin gene related
      peptide, nitric oxide synthase, vesicular acetylcholine transporter, and tyrosine
      hydroxylase. Measurements of urethral wall compliance were taken along its length
      and in different axes using a closed ended catheter with a circular aperture. The
      bladder neck and proximal urethra are characterized by a highly folded epithelium
      and lamina propria. A smooth muscle layer is apparent but not pronounced. Distal
      to this region the smooth muscle layer thickens and forms the body of the
      internal sphincter, which has a complex innervation. In the mid urethra, the
      smooth muscle is thickened resulting in a luminal protrusion, producing an
      occlusion of the lumen. The structure of the distal urethra is different. The
      epithelium has few folds and, immediately below the lamina propria large thin
      walled vascular lacunae can be found. Measurements of the urethral wall
      compliance demonstrate distinct regional differences with proximal and distal
      specialisations. These variations, which correlate with muscular and vascular
      elements, suggest the operation of discrete systems, hence effecting urethral
      closure during filling. An understanding of these systems may yield insights into
      urethral pathology and direct approaches to develop pharmacological interventions
      to promote continence. Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29451374
TI  - [Post-surgical meningitis by Gemella haemolysans].

PMID- 29451375
TI  - [Prevalence and phylogenetic analysis of Chlamydia trachomatis in a population of
      women in Posadas, Misiones].
AB  - OBJECTIVE: Chlamydia trachomatis is the most prevalent bacteria causing sexually
      transmitted infections. In women, this infection can cause cervicitis and
      urethritis, although it's usually asymptomatic. The aim of this study was to
      investigate the prevalence of C. trachomatis in women attending the lab Instituto
      de Prevision Social and detect the genotypes. METHODS: Endocervical samples from
      505 symptomatic and asymptomatic women were assayed. It was determined the
      presence of C. trachomatis by PCR through amplification of a fragment of the
      cryptic plasmid. Positive samples were genotyped by the partial amplification of
      the ompA gene and analyzed phylogenetically. RESULTS: Forty-three positive
      samples were detected to infection with C. trachomatis, obtaining a prevalence of
      8.5% (IC 95%: 6.4-11.3%). The prevalence of C. trachomatis was higher in women
      with vaginal symptoms [11.3% (30/265) vs. 5.4% (13/240)] (p = 0.018), as well as
      in women under 26 year-old [11.5% (28/244) vs. 6.2% (15/246)] (p = 0.021). Based
      on phylogenetic analysis, it was observed that 62% of the samples were genotype
      E, 15% genotype J, 15% genotype D, and 8% genotype F. CONCLUSIONS: This work is
      the first contribution on the molecular epidemiology of C. trachomatis in the
      Misiones province, Argentina, which shows the rate of prevalence of this
      bacterium and offers information on circulating genotypes.

PMID- 29451377
TI  - Erratum: "A Biomonitoring Study of Lead, Cadmium, and Mercury in the Blood of New
      York City Adults".
AB  - [This corrects the article DOI: 10.1289/ehp.10056.].

PMID- 29451376
TI  - [Phage therapy, an alternative to antibiotic therapy?)].
AB  - Bacteriophages are viruses that infect and parasitize bacteria. They can present
      a lytic cycle that determines the lysis of the infected bacteria. Each phage is
      specific to a particular bacterial genus or species. The current increase in the
      incidence of antibiotic resistance in human bacteria has favored the study of
      phages as a therapeutic alternative (phage therapy). Previous studies have shown
      the efficacy of these elements in cutaneous and intestinal infections. Different
      clinical trials are underway to establish the safety, reactogenicity and
      therapeutic efficacy of multiple phage. Being active elements, phages must
      undergo rigorous quality controls to ensure the absence of undesirable effects.
      The bacterial lysis that they cause is of a magnitude inferior to the one
      provoked by the antibiotics. As problems to be solved in the future are the
      possibility of using mixtures of several phages, establish the ideal route of
      administration and modify them genetically to deactivate bacterial resistance
      genes.

PMID- 29451378
TI  - [Spatial distribution and ecological structure of Thalassia testudinum
      (Hydrocharitaceae) in two reefs of Veracruz Reef System National Park, Mexico].
AB  - Seagrasses in coastal environments have been threatened by increased human
      activities; these have negatively altered processes and environmental services,
      and have decreased grassland areas. The aim of this study was to generate
      knowledge of Thalassia testudinumdistribution, state of the structure and
      fragmentation level in two reefs of the Veracruz Reef System NationalPark
      (PNSAV). Two different reefs were selected: Sacrificios in the North and near the
      coast, and Cabezo inthe South and away from the coast. Shoot-specific and area
      specific characteristics of submerged macrophytesmeadows present were determined,
      and four morpho-functional groups were identified. Significant differencesbetween
      plant coverage were tested through nonparametric ANOVA, Kruskal-Wallis test. A
      supervised classificationof spatial high-resolution image verified with field
      data was performed (55 Sacrificios and 290 Cabezo).The fragmentation level was
      calculated using landscape metrics, class level and thematic maps were made
      basedon four covers. The meadows were dominated by Thalassia testudinum; maximum
      densities were 208 shoot/m2in Cabezo, and 176 shoot/m2 in Sacrificios. Cabezo
      presented grasses with short (9 cm) and thin leaves (0.55cm) on average; while
      Sacrificios showed longer (23.5 cm) and thicker (1 cm) leaves. Sacrificios showed
      lowerfragmentation degree than Cabezo; in both cases, the vegetation cover
      fragmentation corresponded to less than50 %. Although Cabezo reef presents
      further fragmentation, which creates a large number of microenvironments,being
      recognized for its importance as recruitment area. This work serves as a baseline
      for the creationof an adequate management plan (formation of a core area of
      Cabezo). It is necessary to complement this workwith new efforts for the
      recognition of seagrass prairies in all PNSAV reefs, as well as periodic
      monitoring andrecognition of ecosystem services. .

PMID- 29451379
TI  - [Effect of temperature and salinity on the reproductive cycle of males and
      females of Crassostrea virginica (Bivalvia: Ostreidae)].
AB  - The American oyster, Crassostrea virginica, is one of the most important
      economiccoastal fishery activities in Mexico. As for other bivalve molluscs, its
      sustainability is based on healthypopulations, and additional information on
      current reproductive cycles, will reinforce local management strategies.The
      objective of this study was to evaluate the effect of temperature and salinity on
      the gonadal developmentstages in both sexes and in two size groups (40-60 mm and
      >= 61 mm) of C. virginica from TamiahuaLagoon, Gulf of Mexico. Monthly surveys of
      90 organisms were undertaken, for a yearly total of 1 080 oysterssampled from the
      lagoon in 2011. Both field and laboratory work used standard procedures. Our
      results showedthat reproduction was continuous in both sexes, but some peaks of
      the reproductive cycle were observed alongthe year. Peaks registered from January
      to July were for gametogenesis; those of June and September were formature
      individuals; and in January, February, and from September to December, for
      spawning/spent oysters.Maturity of females of both range sizes was positively
      correlated with temperature, but not for males. For spawning,spent individuals,
      males of sizes >= 61 mm were positively correlated with salinity, whereas smaller
      males(40-60 mm) and females of both sizes, did not show any correlation. In this
      study, we observed that temperatureand salinity had a different effect in the
      reproduction of the American oyster of different sizes and sexes ofTamiahua
      lagoon.

PMID- 29451380
TI  - What deters plant colonization in a tropical pine plantation?
AB  - Pine plantations in the tropics are often employed to recondition eroded slopes
      from mudslides, as thePinus caribaea plantation that shields the Universidad
      Simon Bolivar campus in Caracas (Venezuela). However,mismanagement of this
      plantation has led to its rapid degradation. The best option to maintain the
      protectiveservice is to restore the plantation and direct its successional
      trajectory towards the neighbouring montane forest.Through experimental
      manipulation, we aimed to determine which factors block secondary succession and
      toinvestigate their effects. Within the experimental constraints imposed by the
      plantation small area, we analysedthe effects of light and fertility limitation,
      litter accumulation and access to seed on plantation restoration.
      Lightavailability was manipulated by clearing and thinning three 800 m2 main
      plots. Fertilization and litter removalwas applied to sub-plots within the light
      plots. Soils were analysed, microclimate was monitored and, for fouryears, stem
      density, species richness and basal area were tallied. Our results showed that
      light accessibility wasthe main factor deterring the successional trajectory of
      the plots, with varying grades of interaction with thesub-treatments. By the end
      of the fourth year, the cleared plot showed the largest responses in all traits
      (triplicatingstem density and basal area and >20 times higher species richness).
      The main colonizers were Crotonmegalodendron, Ocotea fendleri, and Clusia spp.
      all dominant trees in the nearby native forest. We concludedthat the results of
      this pioneer study, showed that small clearings, repeated in 3-4 year cycles are
      appropriatefor similar restoration schemes. This procedure would create a mosaic
      of vegetation patches at different successionalstages while protecting the slopes
      from erosion and increasing local biodiversity.

PMID- 29451382
TI  - Carbon Nanotube Formic Acid Sensors Using a Nickel Bis( ortho
      diiminosemiquinonate) Selector.
AB  - Formic acid is corrosive, and a sensitive and selective sensor could be useful in
      industrial, medical, and environmental settings. We present a chemiresistor for
      detection of formic acid composed of single-walled carbon nanotubes (CNTs) and
      nickel bis( ortho-diiminosemiquinonate) (1), a planar metal complex that can act
      as a ditopic hydrogen-bonding selector. Formic acid is detected in concentrations
      as low as 83 ppb. The resistance of the material decreases on exposure to formic
      acid, but slightly increases on exposure to acetic acid. We propose that 1
      assists in partial protonation of the CNT by formic acid, but the response toward
      acetic acid is dominated by inter-CNT swelling. This technology establishes CNT
      based chemiresistive discrimination between formic and acetic acid vapors.

PMID- 29451381
TI  - From a Highly Disordered to a Metastable State: Uncovering Insights of alpha
      Synuclein.
AB  - alpha-Synuclein (alphaS) is a major constituent of Lewy bodies, the insoluble
      aggregates that are the hallmark of one of the most prevalent neurodegenerative
      disorders, Parkinson's disease (PD). The vast majority of experiments in vitro
      and in vivo provide extensive evidence that a disordered monomeric form is the
      predominant state of alphaS in water solution, and it undergoes a large-scale
      disorder-to-helix transition upon binding to vesicles of different types.
      Recently, another form, tetrameric, of alphaS with a stable helical structure was
      identified experimentally. It has been shown that a dynamic intracellular
      population of metastable alphaS tetramers and monomers coexists normally; and the
      tetramer plays an essential role in maintaining alphaS homeostasis. Therefore, it
      is of interest to know whether the tetramer can serve as a means of preventing or
      delaying the start of PD. Before answering this very important question, it is,
      first, necessary to find out, on an atomistic level, a correlation between
      tetramers and monomers; what mediates tetramer formation and what makes a
      tetramer stable. We address these questions here by investigating both monomeric
      and tetrameric forms of alphaS. In particular, by examining correlations between
      the motions of the side chains and the main chain, steric parameters along the
      amino-acid sequence, and one- and two-dimensional free-energy landscapes along
      the coarse-grained dihedral angles gamma and delta and principal components,
      respectively, in monomeric and tetrameric alphaS, we were able to shed light on a
      fundamental relationship between monomers and tetramers, and the key residues
      involved in mediating formation of a tetramer. Also, the reasons for the
      stability of tetrameric alphaS and inability of monomeric alphaS to fold are
      elucidated here.

PMID- 29451383
TI  - Arsenic Speciation in Mekong Delta Sediments Depends on Their Depositional
      Environment.
AB  - Arsenic contamination in groundwater is pervasive throughout deltaic regions of
      Southeast Asia and threatens the health of millions. The speciation of As in
      sediments overlying contaminated aquifers is poorly constrained. Here, we
      investigate the chemical and mineralogical compositions of sediment cores
      collected from the Mekong Delta in Vietnam, elucidate the speciation of iron and
      arsenic, and relate them to the sediment depositional environment. Gradual
      dissolution of ferric (oxyhydr)oxides with depth is observed down to 7 m,
      corresponding to the establishment of reducing conditions. Within the reduced
      sediment, layers originating from marine, coastal or alluvial depositional
      environments are identified and their age is consistent with a late Holocene
      transgression in the Mekong Delta. In the organic matter- and sulfur-rich layers,
      arsenic is present in association with organic matter through thiol-bonding and
      in the form of arsenian pyrite. The highest arsenic concentration (34-69 ppm) is
      found in the peat layer at 16 m and suggests the accumulation of arsenic due to
      the formation of thiol-bound trivalent arsenic (40-55%) and arsenian pyrite (15
      30%) in a paleo-mangrove depositional environment (~8079 yr BP). Where sulfur is
      limited, siderite is identified, and oxygen- and thiol-bound trivalent arsenic
      are the predominant forms. It is also worth noting that pentavalent arsenic
      coordinated to oxygen is ubiquitous in the sediment profile, even in reduced
      sediment layers. But the identity of the oxygen-bound arsenic species remains
      unknown. This work shows direct evidence of thiol-bound trivalent arsenic in the
      Mekong Delta sediments and provides insight to refine the current model of the
      origin, deposition, and release of arsenic in the alluvial aquifers of the Mekong
      Delta.

PMID- 29451385
TI  - Control of Photomechanical Crystal Twisting by Illumination Direction.
AB  - Photomechanical molecular crystals have been investigated as mesoscopic
      photoactuators. Here, we report how the photomechanical twisting of 1,2-bis(2
      methyl-5-phenyl-3-thienyl)perfluorocyclopentene (1a) crystals depends on
      illumination direction. The ribbon-like crystal of 1a could be successfully
      prepared by a sublimation method. The ribbon crystal exhibited reversible
      photomechanical crystal twisting upon alternating irradiation with ultraviolet
      (UV) and visible light. Moreover, changing the UV illumination direction with
      respect to the crystal resulted in different twisting modes, ranging from
      helicoid to cylindrical. Control of photomechanical crystal deformation by
      illumination direction provides a convenient and useful way to generate a variety
      of photomechanical motions from a single crystal.

PMID- 29451384
TI  - Highly Elastic Biodegradable Single-Network Hydrogel for Cell Printing.
AB  - Cell printing is becoming a common technique to fabricate cellularized printed
      scaffold for biomedical application. There are still significant challenges in
      soft tissue bioprinting using hydrogels, which requires live cells inside the
      hydrogels. Moreover, the resilient mechanical properties from hydrogels are also
      required to mechanically mimic the native soft tissues. Herein, we developed a
      visible-light cross-linked, single-network, biodegradable hydrogel with high
      elasticity and flexibility for cell printing, which is different from previous
      highly elastic hydrogel with double-network and two components. The single
      network hydrogel using only one stimulus (visible light) to trigger gelation can
      greatly simplify the cell printing process. The obtained hydrogels possessed high
      elasticity, and their mechanical properties can be tuned to match various native
      soft tissues. The hydrogels had good cell compatibility to support fibroblast
      growth in vitro. Various human cells were bioprinted with the hydrogels to form
      cell-gel constructs, in which the cells exhibited high viability after 7 days of
      culture. Complex patterns were printed by the hydrogels, suggesting the hydrogel
      feasibility for cell printing. We believe that this highly elastic, single
      network hydrogel can be simply printed with different cell types, and it may
      provide a new material platform and a new way of thinking for hydrogel-based
      bioprinting research.

PMID- 29451386
TI  - Optically Switchable Photocatalysis in Ultrathin Black Phosphorus Nanosheets.
AB  - Recently low-dimensional materials hold great potential in the field of
      photocatalysis, whereas the concomitantly promoted many-body effects have long
      been ignored. Such Coulomb interaction-mediated effects would lead to some
      intriguing, nontrivial band structures, thus promising versatile photocatalytic
      performances and optimized strategies. Here, we demonstrate that ultrathin black
      phosphorus (BP) nanosheets exhibit an exotic, excitation-energy-dependent,
      optical switching effect in photocatalytic reactive oxygen species (ROS)
      generation. It is, for the first time, observed that singlet oxygen (1O2) and
      hydroxyl radical (*OH) are the dominant ROS products under visible- and
      ultraviolet-light excitations, respectively. Such an effect can be understood as
      a result of subband structure, where energy-transfer and charge-transfer
      processes are feasible under excitations in the first and second subband systems,
      respectively. This work not only establishes an in-depth understanding on the
      influence of many-body effects on photocatalysis but also paves the way for
      optimizing catalytic performances via controllable photoexcitation.

PMID- 29451387
TI  - The Mystery of the AuIn 1:1 Phase and Its Incommensurate Structural Variations.
AB  - In this communication, the AuIn 1:1 phase ( Naturwissenschaften , 1953 , 40 , 437
      , DOI: 10.1007/BF00590353 ), and its ordering behavior at various temperatures is
      investigated. To enable the growth of a X-ray suitable specimen, a tempering
      routine was established by the interpretation of a differential scanning
      calorimetry (DSC) study. In this way, good quality single crystals were grown and
      measured at the Crystal beamline at Synchrotron SOLEIL. From the acquired data,
      three variations of this structure could be found at temperatures of 400  degrees
      C and 300  degrees C and room temperature, with differing degrees of
      incommensurate modulation. Diffuse scattering found at 400  degrees C was
      interpreted with the help of a three-dimensional difference pair distribution
      function (3D-DeltaPDF) study.

PMID- 29451388
TI  - Dual Inhibitor of Staphylococcus aureus Virulence and Biofilm Attenuates
      Expression of Major Toxins and Adhesins.
AB  - Staphylococcus aureus is a major bacterial pathogen that invades and damages host
      tissue by the expression of devastating toxins. We here performed a phenotypic
      screen of 35 molecules that were structurally inspired by previous hydroxyamide
      based S. aureus virulence inhibitors compiled from commercial sources or designed
      and synthesized de novo. One of the most potent compounds, AV73, not only reduced
      hemolytic alpha-hemolysin production in S. aureus but also impeded in vitro
      biofilm formation. The effect of AV73 on bacterial proteomes and extracellular
      protein levels was analyzed by quantitative proteomics and revealed a significant
      down-regulation of major virulence and biofilm promoting proteins. To elucidate
      the mode of action of AV73, target identification was performed using affinity
      based protein profiling (AfBPP), where among others YidC was identified as a
      target.

PMID- 29451389
TI  - Molecular Dynamics Study of Hydrophilic Sphalerite (110) Surface as Modified by
      Normal and Branched Butylthiols.
AB  - Molecular dynamics simulation was used to study the wettability of the
      hydrophilic sphalerite (110) surface chemically modified by butylthiols made up
      of normal and branched alkyl tails, referred to as n-butylthiol and i-butylthiol
      hereafter, at different adsorption site coverages. Butylthiol molecules were
      grafted onto the adsorption sites of the surface in two different distributions
      ordered and random. The results showed that for a given butylthiol at a given
      site coverage, random surface distribution yielded a slightly larger contact
      angle. This observation was attributed to the fact that average distances between
      the first and second nearest neighbors of butylthiol molecules are shorter in the
      case of random surface distribution, resulting in smaller patches of bare surface
      exposed to water molecules compared to those of the ordered surface distribution.
      Regardless of the tail structure, the random surface distribution exhibited
      hydrophobic character (i.e., contact angle >= 90 degrees ) at a relatively low
      site coverage of about 25%. The test area method and the Kirkwood and Buff
      approach were adopted to estimate surface energies (gammaSV) of the bare
      sphalerite (110) surface and the collector monolayer, respectively. Using the
      obtained gammaSV values of these two pure states, the apparent surface energy as
      a function of surface coverage was determined based on Cassie's law. This allowed
      us to estimate the corresponding values of solid-liquid apparent interfacial
      tension (gammaSL). Both gammaSV and gammaSL exhibit a linear inverse dependence
      on surface coverage with a crossover point at 25% site coverage (about 50%
      surface coverage), above which gammaSV falls below gammaSL, leading to contact
      angles greater than 90 degrees . The results also revealed that contact angles of
      the two butylthiols are comparable at site coverages below ~85%, but above that,
      they are significantly lower for the branched thiols compared to their normal
      counterparts. Considering the Lennard-Jones interaction energies between the
      water cluster and the butylthiols, stronger attractive interactions were present
      in the case of i-butylthiol due to the presence of two methyl groups in its alkyl
      chain. This difference was the most intense at site coverages above ~85%.

PMID- 29451390
TI  - Vacuum Ultraviolet Treatment of Acid- and Ester-Terminated Self-Assembled
      Monolayers: Chemical Conversions and Friction Reduction.
AB  - We have prepared COOH- and COOCH3-terminated self-assembled monolayers (SAMs)
      from undec-10-enoic acid (UDA) and methyl undec-10-enoate (MUDO) molecules on
      hydrogen-terminated silicon (H-Si) substrates through ultraviolet (UV)
      irradiation. The as-prepared UDA- and MUDO-SAMs were exposed to 172 nm vacuum-UV
      (VUV) light in a high vacuum environment (HV, <10-3 Pa) for different periods.
      The presence of COO components at the surfaces of these SAMs without prior
      oxidation would simplify the understanding of the origin of the chemical
      conversions and the changes of surface properties, as the prior oxidation would
      change the surface properties and generate different oxygenated groups. After the
      HV-VUV treatment, the abundance of COOH and COOCH3 components of these SAMs
      decreased without significant dissociation of their C-C backbones. Degradation of
      these components occurred through dissociating their C-O bonds, resulting in
      different C?O components. Also, the occurrence of Norrish type pathways resulted
      in a slight decrease of carbon content and produced CH3 components. We have
      applied the HV-VUV lithography to control the abundance of COOH and COOCH3
      components in well-defined areas and to investigate the friction differences
      between the irradiated and masked areas. The irradiated areas exhibited lower
      friction than the masked areas without observing significant height contrasts
      between these areas. The reduction in friction was attributed to the conversion
      of the COOH and COOCH3 components to less adhesive components such as C?O and
      CH3. These experiments suggest the HV-VUV treatments as an approach for low
      damage dry surface modifications and reductive lithographic techniques at
      surfaces terminated by acid and ester groups.

PMID- 29451391
TI  - The future of LC-MS for pharmaceutical analysis: an interview with Jun Qu.
AB  - Jun Qu speaks to Sankeetha Nadarajah, Editor of Bioanalysis: Jun Qu is the group
      leader of the proteomics and pharmaceutical analysis lab of SUNY-Buffalo (NY,
      USA) and a Professor in the Department of Pharmaceutical Sciences. His research
      is focused on the study of Clinical and Pharmaceutical Proteomics and
      Pharmaceutical Analysis using LC-MS-based strategies. His research programs
      include high-resolution and large-scale expression profiling of pathological
      proteomes, for the discovery of novel disease/therapeutics biomarkers using gel
      free proteomic methods; sensitive identification, localization and quantification
      of post-translational modifications in tissue proteomes such as these in
      myocardium, using novel anti-PTM affinity capture and alternating Collision
      induced dissociation/Electron transfer dissociation to obtain abundant PTM
      information; targeted investigation of marker proteins that are of high interests
      for clinical and pharmaceutical study, using highly sensitive nano-LC/SRM-based
      methods; and highly sensitive and accurate investigation of the PK of
      biotherapeutics using LC-MS.

PMID- 29451392
TI  - Evaluation of cAMS for 14C microtracer ADME studies: opportunities to change the
      current drug development paradigm.
AB  - AIM: Although regulatory guidances require human metabolism information of drug
      candidates early in the development process, the human mass balance study (or
      hADME study), is performed relatively late. hADME studies typically involve the
      administration of a 14C-radiolabelled drug where biological samples are measured
      by conventional scintillation counting analysis. Another approach is the
      administration of therapeutic doses containing a 14C-microtracer followed by
      accelerator mass spectrometry (AMS) analysis, enabling hADME studies completion
      much earlier. Consequently, there is an opportunity to change the current drug
      development paradigm. MATERIALS & METHODS: To evaluate the applicability of the
      MICADAS-cAMS method, we successfully performed: the validation of MICADAS-cAMS
      for radioactivity quantification in biomatrices and, a rat ADME study, where the
      conventional methodology was assessed against a microtracer MICADAS-cAMS
      approach. RESULTS & DISCUSSION: Combustion AMS (cAMS) technology is applicable to
      microtracer studies. A favorable opinion from EMA to complete the hADME in a
      Phase I setting was received, opening the possibilities to change drug
      development.

PMID- 29451393
TI  - Cleaning at Home and at Work in Relation to Lung Function Decline and Airway
      Obstruction.
AB  - RATIONALE: Cleaning tasks may imply exposure to chemical agents with potential
      harmful effects to the respiratory system, and increased risk of asthma and
      respiratory symptoms among professional cleaners and in persons cleaning at home
      has been reported. Long-term consequences of cleaning agents on respiratory
      health are, however, not well described. OBJECTIVES: This study aimed to
      investigate long-term effects of occupational cleaning and cleaning at home on
      lung function decline and airway obstruction. METHODS: The European Community
      Respiratory Health Survey (ECRHS) investigated a multicenter population-based
      cohort at three time points over 20 years. A total of 6,235 participants with at
      least one lung function measurement from 22 study centers, who in ECRHS II
      responded to questionnaire modules concerning cleaning activities between ECRHS I
      and ECRHS II, were included. The data were analyzed with mixed linear models
      adjusting for potential confounders. MEASUREMENTS AND MAIN RESULTS: As compared
      with women not engaged in cleaning (DeltaFEV1 = -18.5 ml/yr), FEV1 declined more
      rapidly in women responsible for cleaning at home (-22.1; P = 0.01) and
      occupational cleaners (-22.4; P = 0.03). The same was found for decline in FVC
      (DeltaFVC = -8.8 ml/yr; -13.1, P = 0.02; and -15.9, P = 0.002; respectively).
      Both cleaning sprays and other cleaning agents were associated with accelerated
      FEV1 decline (-22.0, P = 0.04; and -22.9, P = 0.004; respectively). Cleaning was
      not significantly associated with lung function decline in men or with FEV1/FVC
      decline or airway obstruction. CONCLUSIONS: Women cleaning at home or working as
      occupational cleaners had accelerated decline in lung function, suggesting that
      exposures related to cleaning activities may constitute a risk to long-term
      respiratory health.

PMID- 29451394
TI  - Clinical application of microsampling versus conventional sampling techniques in
      the quantitative bioanalysis of antibiotics: a systematic review.
AB  - Conventional sampling techniques for clinical pharmacokinetic studies often
      require the removal of large blood volumes from patients. This can result in a
      physiological or emotional burden, particularly for neonates or pediatric
      patients. Antibiotic pharmacokinetic studies are typically performed on healthy
      adults or general ward patients. These may not account for alterations to a
      patient's pathophysiology and can lead to suboptimal treatment. Microsampling
      offers an important opportunity for clinical pharmacokinetic studies in
      vulnerable patient populations, where smaller sample volumes can be collected.
      This systematic review provides a description of currently available
      microsampling techniques and an overview of studies reporting the quantitation
      and validation of antibiotics using microsampling. A comparison of microsampling
      to conventional sampling in clinical studies is included.

PMID- 29451395
TI  - Determining the Consistency of Resolved Triplets and Fan Triplets.
AB  - The [Formula: see text] Consistency problem takes as input two sets [Formula: see
      text] and [Formula: see text] of resolved triplets and two sets [Formula: see
      text] and [Formula: see text] of fan triplets, and asks for a distinctly leaf
      labeled tree that contains all elements in [Formula: see text] and no elements in
      [Formula: see text] as embedded subtrees, if such a tree exists. This article
      presents a detailed characterization of how the computational complexity of the
      problem changes under various restrictions. Our main result is an efficient
      algorithm for dense inputs satisfying [Formula: see text] whose running time is
      linear in the size of the input and therefore optimal.

PMID- 29451396
TI  - Vacuum assisted breast biopsy (VAB) excision of subcentimeter microcalcifications
      as an alternative to open biopsy for atypical ductal hyperplasia.
AB  - OBJECTIVE: Atypical ductal hyperplasia (ADH) is a proliferative lesion associated
      with a variable increased risk of breast malignancy, but the management of the
      patients is still not completely defined, with mandatory surgical excision in
      most cases. To report the results of the conservative management with
      mammographic checks of patients with ADH diagnosed by vacuum assisted breast
      biopsy (VAB), without residual calcifications. METHODS: The authors accessed the
      institutional database of radiological, surgical and pathological anatomy.
      Inclusion criteria were: ADH diagnosed by VAB on a single group of
      microcalcifications, without residual post-procedure; follow-up at least of 12
      months. Exclusion criteria were the presence of personal history of breast cancer
      or other high-risk lesions; association with other synchronous lesions, both more
      and less advanced proliferative lesions. RESULTS: The 65 included patients were
      all females, with age range of 40-79 years (mean 54 years). The maximum diameter
      range of the groups of microcalcifications was 4-11 mm (mean 6.2 mm), all
      classified as BI-RADS 4b (Breast Imaging Reporting and Data System 4b) and
      defined as fine pleomorphic in 29 cases (45%) or amorphous in 36 cases (55%). The
      range of follow-up length was 12-156 months (mean 67 months). Only one patients
      developed new microcalcifications, in the same breast, 48 months after and 15 mm
      from the first VAB, interpreted as low-grade ductal carcinoma in situ (DCIS) at
      surgical excision. CONCLUSION: These results could justify the conservative
      management, in a selected group of patients, being the malignancy rate lower than
      2%, considered in the literature as the "probably benign" definition. Advances in
      knowledge: Increasing the length of follow-up of selected patients conservatively
      managed can improve the management of ADH cases.

PMID- 29451398
TI  - Examining heat treatment for stabilization of the lipidome.
AB  - AIM: To confidently determine lipid-based biomarkers, it is important to minimize
      variation introduced during preanalytical steps. We evaluated reducing variation
      associated with lipid measurements in invertebrate sentinel species using a state
      of-the-art heat treatment technique. MATERIALS AND METHODS: Earthworms (Eisenia
      fetida), house crickets (Acheta domestica) and ghost shrimp (Palaemonetes
      paludosus) were euthanized either by flash freezing or heat treatment. For both
      experiments, samples were either immediately extracted after removal from -80
      degrees C storage or incubated on ice for one hour prior to sample weighing and
      extraction. Lipidomics was performed on resulting extracts using liquid
      chromatography high resolution tandem mass spectrometry. LipidMatch and
      LipidSearch were used for lipid identification. RESULTS: Lipid enzymatic products
      (e.g., phosphatidylmethanols, diglycerides, lysoglycerophospholipids and ether
      linked/oxidized lysoglycerophospholipids), were in higher concentrations in flash
      frozen samples, when compared with heat-treated samples. Results suggest that
      heat treatment reduces phospholipase A and phospholipase D activity. CONCLUSION:
      Heat treatment reduced enzymatic products and increased precursors of these
      enzymatic products. We believe heat treatment warrants a closer interrogation for
      improving the robustness of lipid biomarker research, especially in tissue
      samples, where enzyme stabilizers are difficult to apply, and for use in field
      studies, where the stabilization of the collected sample is critical.

PMID- 29451399
TI  - Assistive technology for communication of older adults: a systematic review.
AB  - OBJECTIVE: Describe the use of assistive technology to enhance communication
      opportunities for older adults. METHODS: A systematic review was conducted in two
      databases, PubMed and Web of Science, by using two different searches in each.
      The search was limited to original articles, in English language, including
      people aged 60 years and older that used any type of assistive technology for
      communication. The articles found in the initial search were filtered by title,
      abstracts and the remaining articles were fully read. RESULTS: Eighteen studies
      were included in this review after the reading of full-texts. Most of the studies
      included apparently healthy participants with communication limitations due to
      aging related changes and the others included people with some pathology that
      prevent them from normal communication. CONCLUSION: Four categories of assistive
      technology were identified: assistive technology for people with speech problems;
      robot or videoconferencing systems; Information and Communication Technologies
      and, other types of assistive technology for communication, such as hearing aids
      and scrapbooks. Assistive technology for communication of older adults is not
      only used by people with disabilities that prevent them from usual communication.
      They are mostly for older adults without a pathological communication problem.

PMID- 29451400
TI  - Designing selective modulators for the nicotinic receptor subtypes: challenges
      and opportunities.
AB  - Nicotinic receptors are membrane proteins involved in several physiological
      processes. They are considered suitable drug targets for various CNS disorders or
      conditions, as shown by the large number of compounds which have entered clinical
      trials. In recent years, nonconventional agonists have been discovered: positive
      allosteric modulators, allosteric agonists, site-specific agonists and silent
      desensitizers are compounds able to modulate the receptor interacting at sites
      different from the orthodox one, or to desensitize the receptor without prior
      opening. While these new findings can further complicate the pharmacology of
      these proteins and the design and optimization of ligands, they undoubtedly offer
      new opportunities to find drugs for the many therapeutic indications involving
      nicotinic receptors.

PMID- 29451401
TI  - Abstracts from the 32nd Annual Meeting of the Engineering and Urology Society May
      12, 2017 Boston, MA.

PMID- 29451402
TI  - Editor's Choice - Frailty and the management of patients with acute
      cardiovascular disease: A position paper from the Acute Cardiovascular Care
      Association.
AB  - Frailty is increasingly seen among patients with acute cardiovascular disease. A
      combination of an ageing population, improved disease survival, treatable long
      term conditions as well as a greater recognition of the syndrome has accelerated
      the prevalence of frailty in the modern world. Yet, this has not been matched by
      an expansion of research. National and international bodies have identified acute
      cardiovascular disease in the frail as a priority area for care and an entity
      that requires careful clinical decisions, but there remains a paucity of guidance
      on treatment efficacy and safety, and how to manage this complex group. This
      position paper from the Acute Cardiovascular Care Association presents the latest
      evidence about frailty and the management of frail patients with acute
      cardiovascular disease, and suggests avenues for future research.

PMID- 29451403
TI  - Assessment of MRI findings and clinical symptoms in patients with
      temporomandibular joint disorders.
AB  - OBJECTIVES: To investigate the correlations among various temporomandibular joint
      (TMJ) findings on MRI and the relationships between MRI findings and symptoms.
      METHODS: 425 patients (850 TMJs) with temporomandibular joint disorders (TMDs)
      who underwent MRI were enrolled. Oblique sagittal proton density-weighted and T2
      weighted images in open- and closed-mouth positions were evaluated. MRI findings
      included disc configuration, disc position, condylar morphology, bone marrow
      pattern, and joint effusion. Symptoms included TMJ pain, TMJ noise, and
      limitation of mouth opening. For statistical analyses, Spearman's rank
      correlation coefficient and logistic regression analysis were applied. RESULTS:
      Folded disc, disc displacement without reduction (DDWOR), and osteophytes had
      significant negative correlations with other normal MRI findings (p < 0.01).
      DDWOR and marrow edema were associated with TMJ pain. Conversely, osteophytes
      [odds ratio (OR): 0.52; 95% CI (0.30-0.90)] and combination-type condylar
      degeneration [OR: 0.45; 95% CI (0.24-0.83)] were associated with decreased risk
      of TMJ pain. Condylar flattening was positively associated with TMJ noise [OR:
      5.25; 95% CI (1.44-19.07)] and negatively associated with limitation of mouth
      opening [OR: 0.34; 95% CI (0.11-0.99)]. High-grade joint effusion was
      significantly associated with TMJ pain and noise. CONCLUSIONS: DDWOR and high
      grade joint effusion (an indicator of inflammation in the articular cavity) were
      associated with TMD symptoms. This finding suggests that treatment strategy for
      DDWOR and decreasing inflammation might lessen clinical TMD symptoms. Condylar
      degeneration was not associated with indicators of inflammation or TMJ symptoms.
      These results suggest that patients with TMD symptoms should undergo initial MRI
      to allow rapid selection of appropriate therapies.

PMID- 29451404
TI  - Optimizing NBE PK/PD assays using the Gyrolab Affinity Software; conveniently
      within the bioanalyst's existing workflow.
AB  - AIM: The fully automated microfluidics-based Gyrolab is a popular instrument for
      the bioanalysis of protein therapeutics; requiring minimal sample and reagent
      volumes. Gyros offers affinity software for determining binding affinity in
      solution using a high-throughput method and miniaturized reactions. RESULTS:
      Using this affinity software, multiple CTGF-targeting reagents were characterized
      on the Gyrolab after <100% target coverage was seen in a cynomolgus
      pharmacokinetic/PD study dosed with anti-CTGF antibodies. The results uncovered
      magnitude differences in binding affinities between the dosed antibody, target
      and assay reagents. CONCLUSION: The binding affinity values were used to
      investigate reduced target coverage and results highlight potential of the
      affinity software for incorporation into the bioanalyst's existing Gyrolab
      workflow for characterizing reagents and optimizing pharmacokinetic/PD
      bioanalytical assays.

PMID- 29451405
TI  - Astragalus polysaccharide alleviates LPS-induced inflammation injury by
      regulating miR-127 in H9c2 cardiomyoblasts.
AB  - Astragalus polysaccharide (APS) has been widely reported to play an important
      role in inflammatory response. In this study, we aimed to explore the effects and
      underlying mechanisms of APS on lipopolysaccharide (LPS)-induced inflammation
      injury in H9c2 cardiomyoblasts. H9c2 cells were treated with different
      concentrations of APS, and cell viability was detected by the Cell Counting Kit-8
      (CCK-8) assay. Then, the effect of APS on cell viability and apoptosis induced by
      LPS was determined by CCK-8, flow cytometry, and western blot. The expression and
      release of inflammatory cytokines were evaluated by quantitative real-time
      polymerase chain reaction (qRT-PCR), western blot, and enzyme-linked
      immunosorbent assay (ELISA). Furthermore, expression of miR-127 in H9c2 cells was
      analyzed by qRT-PCR, and knocked down by transfection with miR-127 inhibitor.
      Western blot was used to analyze signaling pathway molecules. APS had no effect
      on H9c2 cells viability. However, APS could alleviate LPS-induced inflammation
      injury by increasing cell viability, reducing apoptosis, and inhibiting release
      of inflammatory cytokines in H9c2 cells ( P < 0.05). Additionally, we found that
      APS increased toll-like receptor 4 (TLR4) expressions in LPS-treated H9c2 cells.
      Mechanistically, we found that APS exerted the protective effect by down
      regulating LPS-increased expression of miR-127 ( P < 0.05), inhibiting nuclear
      factor kappa B (NF-kappaB), JNK and promoting phosphoinositide 3-kinase/protein
      kinase B (PI3K/AKT) signaling pathways in LPS-treated H9c2 cells. The results
      demonstrated that APS could protect H9c2 cells against LPS-induced inflammation
      injury, which might be partially due to miR-127 down-regulation and regulation of
      NF-kappaB, JNK, and PI3K/AKT signaling pathways. These findings indicated that
      APS might be a potential therapeutic drug for treatment of myocarditis.

PMID- 29451406
TI  - Cancer costs and outcomes for common cancer sites in the Finnish population
      between 2009-2014.
AB  - BACKGROUND: The cost of cancer and outcomes of cancer care have been discussed a
      lot since cancer represents 3-6% of total healthcare costs and cost estimations
      have indicated growing costs. There are studies considering the cost of all
      cancers, but studies focusing on the cost of disease and outcomes in most common
      cancer sites are limited. The objective of this study was to analyze the
      development of the costs and outcomes in Finland between 2009 and 2014 per cancer
      site. METHODS: The National cost, episode and outcomes data were obtained from
      the National register databases based on International Statistical Classification
      of Diseases (ICD)-10 diagnosis codes. Cost data included both the direct and
      indirect costs. Two hospitals were used to validate the costs of care. The
      outcome measures included relative survival rate, mortality, sick leave days per
      patient and number of new disability pensions. FINDINGS: The outcomes of cancer
      care in most common cancer sites have improved in Finland between 2009-2014. The
      real costs per new cancer patient decreased in seven out of ten most common
      cancer sites. The significance of different cost components differ significantly
      between the different cancer sites. The share of medication costs of the total
      cost of all cancers increased, but decreased for the five most common cancer
      sites. INTERPRETATION: The changes in the cost components indicate that the
      length of stay has shortened in special care and treatment methods have developed
      towards outpatient care. This partially explains the decrease of costs. Also, at
      the same time outcomes improved, which indicates that decrease in costs did not
      come at the expense of treatment quality. As the survival rates increase, the
      relevance of mortality measures decreases and the relevance of other, patient
      relevant outcome measures increases. In the future, the outcomes and costs of
      health care systems should be assessed routinely for the most common patient
      groups.

PMID- 29451407
TI  - Advancements in drug development for diarrhea-predominant irritable bowel
      syndrome.
AB  - INTRODUCTION: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common
      disorder characterized by a complex pathophysiology hampering optimal targeted
      drug development. Recent advances in our understanding of key underlying
      mechanisms prompted novel therapeutics including novel pharmacological
      approaches. Areas covered: This review summarizes the latest advancements in the
      pipeline of IBS-D drugs focusing on new pharmacological targets, efficacy and
      safety of medicinal products considering the recent harmonization of regulatory
      requirements by the FDA and the EMA. Expert opinion: The new 5-HT3 receptor
      antagonist ramosetron appears a promising therapeutic approach devoid of
      significant adverse events, although it is presently unavailable in Western
      countries, most likely because of the precautionary approach taken by regulatory
      agencies with this drug class. New pharmacological concepts on full
      agonists/antagonists, mixed-receptor activity and novel drug targets may
      streamline the present drug pipeline along with the adherence on new regulatory
      guidelines on outcome measures. Eluxadoline can be taken as an example of this
      paradigm shift. It has now been granted marketing authorization for IBS-D on both
      sides of the Atlantic, but it is still considered as a second-line agent by the
      NICE. There is still much work to be done to fully cover clinical needs of
      patients with IBS-D.

PMID- 29451408
TI  - Single Nucleotide Polymorphisms in Key One-Carbon Metabolism Genes and Their
      Association with Blood Folate and Homocysteine Levels in a Chinese Population in
      Yunnan.
AB  - OBJECTIVE: One-carbon metabolism (OCM) is essential for DNA synthesis and
      methylation. Single nucleotide polymorphisms (SNPs) within OCM genes may affect
      folic acid (FA) metabolism, disrupt homocysteine (Hcy) homeostasis, and increase
      the risk of disease. This study investigated the relationship between SNPs in key
      OCM genes and their association with blood FA and Hcy levels in a healthy
      population in Yunnan, China. METHODS: Six SNPs within five key OCM genes (MTHFR
      C677T, MTHFR A1298C, MS A2756G, MTRR A66G, CBS T833C, and SHMT C1420T) were
      genotyped in 300 healthy volunteers (148 males and 152 females) using polymerase
      chain reaction/restriction fragment length polymorphism. Blood folate [serum FA
      (SFA) and red blood cell folate (RBC FA)] and Hcy levels were determined by
      chemiluminescence immunoassays and enzymatic assays. RESULTS: Subjects with the
      MTHFR 677TT genotype had significantly higher Hcy levels and RBC FA
      concentrations compared with those harboring the MTHFR 677CC/CT genotypes (p <
      0.01). Both Hcy and blood FA concentrations were also increased in subjects with
      MS 2756AA, as well as those within CBS 833TT, when compared with those with MS
      2756AG/GG (p < 0.05) and CBS 833TC/CC (p < 0.05) genotypes, respectively.
      Subjects harboring the combined genotype of MTHFR 677TT and MS 2756AA had a
      higher Hcy concentration than those carrying other MTHFR and MS combinations (p =
      0.002). Similarly, subjects harboring the combination of CBS 833TT with MTHFR
      677TT had higher Hcy concentrations than those harboring other CBS and MTHFR
      combinations (p = 0.011). CONCLUSIONS: The genotypes involving the MTHFR C677T,
      MS A2756G, and CBS T833C polymorphisms, including combinations of these
      genotypes, were the most important factors associated with blood FA and Hcy
      levels of the investigated SNPs in the OCM genes.

PMID- 29451409
TI  - Temporal trends in incidence and outcome of hydatidiform mole: a retrospective
      cohort study.
AB  - BACKGROUND: Reported incidence rates of hydatidiform mole (HM) show wide
      geographic and temporal variations, making reliable international comparisons
      difficult. The aim of the current study was to examine temporal trends in the
      incidence of HM and post-molar gestational trophoblastic neoplasia (GTN) in
      Stockholm County. MATERIAL AND METHODS: Data of all women with a diagnosis of HM
      in Stockholm County 1991-2010 was collected. The incidence of HM was assessed
      both in relation to number of births and viable conceptions (births and pregnancy
      terminations). The risk of post-molar GTN was analysed for all HM, as well as for
      the subtypes complete (CHM) and partial hydatidiform mole (PHM). Temporal trends
      were analysed by stratifying the study period into five-year intervals. RESULTS:
      The overall incidence rate of HM was 2.08/1000 deliveries and 1.48/1000 viable
      conceptions. A significant temporal increase in the incidence rate of HM, as well
      as in the total number and proportion of PHM, was seen. Among 956 women with HM,
      77 (8%) progressed into post-molar GTN. There was evidence of a slight, but non
      significant increase in the risk of malignancy in the two last five-year periods
      under study. CONCLUSIONS: We found evidence of a significant temporal increase in
      the incidence rate of HM, which could not fully be explained by an increase in
      maternal age over time. Changes in diagnostic methods probably contributed to the
      increased incidence rate of PHM. The risk of post-molar GTN remained constant
      over time.

PMID- 29451410
TI  - Inclisiran for the treatment of dyslipidemia.
AB  - INTRODUCTION: Dyslipidemia is one of the most important risk factors for
      cardiovascular disease. Insufficient reduction in LDL-C from existing therapies
      in patients at high risk of atherogenic cardiovascular disease is an unmet
      clinical need. Circulating PCSK9 causes hypercholesterolemia by reducing LDL
      receptors in hepatocytes. Areas covered: PCSK9 inhibition has emerged as a
      promising new therapeutic strategy to reduce LDL-C. Inclisiran, a novel,
      synthetic, siRNA molecule, inhibits PCSK9 synthesis in hepatocytes. Inclisiran
      targets intracellular PCSK9 synthesis specifically, resulting in a dose
      dependent, long-term, significant reduction in LDL-C. Inclisiran has been well
      tolerated and safe, without severe adverse events so far. This review discusses
      current PCSK9 inhibitors and the results of phase I and II clinical trials of
      inclisiran. Expert opinion: Plasma PCSK9 enhances the degradation of LDL
      receptor, resulting in accumulation of LDL-C in the circulation. Current
      approaches with monoclonal antibodies sequester circulating PCSK9 but require
      frequent injections. Inclisiran inhibits translation of PCSK9 mRNA and thus
      switches off PCSK9 production and provides advantages over monoclonal antibodies
      with an infrequent dosing interval of twice a year to reduce LDL-C by over 50%.
      Ongoing studies will establish the long-term safety of inclisiran in patients
      with high cardiovascular risk and an elevated LDL-C.

PMID- 29451411
TI  - An evaluation of a peer support intervention for student mental health.
AB  - BACKGROUND: Peer support is support provided by and for people with similar
      experiences. As students turn to peers for support with their mental health, peer
      support may provide an opportunity to engage students at an informal level and
      avoid some barriers to help-seeking. AIMS: The study aimed to identify students
      likely to attend peer support and evaluate the acceptability and impact of the
      intervention. METHODS: A six-part peer-led course for mild depression, based on
      behavioural activation and implementation intentions, was evaluated across eight
      UK universities with 65 students participating in the evaluation. The evaluation
      focused on mental wellbeing. RESULTS: Participants were predominately female and
      had been experiencing anxiety or depression for more than one year. Most
      participants had already approached professional services for support. At least
      57% of participants attended more than one session and 34% completed the course.
      Students with lower levels of mental wellbeing were more likely to complete the
      course. For students returning, there was a significant increase in mental
      wellbeing. CONCLUSIONS: Structured peer support for depression may have benefits
      in improving student mental wellbeing. However, this is unlikely to have a
      substantive effect in improving early and preventative intervention.

PMID- 29451412
TI  - Development and validation of a radiomic signature to predict HPV (p16) status
      from standard CT imaging: a multicenter study.
AB  - OBJECTIVES: Human papillomavirus (HPV) positive oropharyngeal cancer
      (oropharyngeal squamous cell carcinoma, OPSCC) is biologically and clinically
      different from HPV negative OPSCC. Here, we evaluate the use of a radiomic
      approach to identify the HPV status of OPSCC. METHODS: Four independent cohorts,
      totaling 778 OPSCC patients with HPV determined by p16 were collected. We
      randomly assigned 80% of all data for model training (N = 628) and 20% for
      validation (N = 150). On the pre-treatment CT images, 902 radiomic features were
      calculated from the gross tumor volume. Multivariable modeling was performed
      using least absolute shrinkage and selection operator. To assess the impact of CT
      artifacts in predicting HPV (p16), a model was developed on all training data
      (Mall) and on the artifact-free subset of training data (Mno art). Models were
      validated on all validation data (Vall), and the subgroups with (Vart) and
      without (Vno art) artifacts. Kaplan-Meier survival analysis was performed to
      compare HPV status based on p16 and radiomic model predictions. RESULTS: The area
      under the receiver operator curve for Mall and Mno art ranged between 0.70 and
      0.80 and was not significantly different for all validation data sets. There was
      a consistent and significant split between survival curves with HPV status
      determined by p16 [p = 0.007; hazard ratio (HR): 0.46], Mall (p = 0.036; HR:
      0.55) and Mno art (p = 0.027; HR: 0.49). CONCLUSION: This study provides proof of
      concept that molecular information can be derived from standard medical images
      and shows potential for radiomics as imaging biomarker of HPV status. Advances in
      knowledge: Radiomics has the potential to identify clinically relevant molecular
      phenotypes.

PMID- 29451413
TI  - Quantitative analysis of enhanced malignant and benign lesions on contrast
      enhanced spectral mammography.
AB  - OBJECTIVE: To retrospectively analyze the quantitative measurement and kinetic
      enhancement among pathologically proven benign and malignant lesions using
      contrast-enhanced spectral mammography (CESM). METHODS: We investigated the
      differences in enhancement between 44 benign and 108 malignant breast lesions in
      CESM, quantifying the extent of enhancements and the relative enhancements
      between early (between 2-3 min after contrast medium injection) and late (3-6
      min) phases. RESULTS: The enhancement was statistically stronger in malignancies
      compared to benign lesions, with good performance by the receiver operating
      characteristic curve [0.877, 95% confidence interval (0.813-0.941)]. Using
      optimal cut-off value at 220.94 according to Youden index, the sensitivity was
      75.9%, specificity 88.6%, positive likelihood ratio 6.681, negative likelihood
      ratio 0.272 and accuracy 82.3%. The relative enhancement patterns of benign and
      malignant lesions, showing 29.92 vs 73.08% in the elevated pattern, 7.14 vs
      92.86% in the steady pattern, 5.71 vs 94.29% in the depressed pattern, and 80.00
      vs 20.00% in non-enhanced lesions (p < 0.0001), respectively. CONCLUSION: Despite
      variations in the degree of tumour angiogenesis, quantitative analysis of the
      breast lesions on CESM documented the malignancies had distinctive stronger
      enhancement and depressed relative enhancement patterns than benign lesions.
      Advances in knowledge: To our knowledge, this is the first study evaluating the
      feasibility of quantifying lesion enhancement on CESM. The quantities of
      enhancement were informative for assessing breast lesions in which the
      malignancies had stronger enhancement and more relative depressed enhancement
      than the benign lesions.

PMID- 29451414
TI  - Comparing methods of misclassification correction for studies of adolescent
      alcohol use.
AB  - BACKGROUND: Despite concerns over measurement error, self-report continues to be
      the most common measure of adolescent alcohol use used by researchers. Objective
      measures of adolescent alcohol use continue to advance; however, they tend to be
      cost prohibitive for larger studies. By combining appropriate statistical
      techniques and validation subsamples, the benefits of objective alcohol measures
      can be made more accessible to a greater number of researchers. OBJECTIVES: To
      compare three easily implemented methods to correct for measurement error when
      objective measures of alcohol use are available for a subsample of participants,
      regression calibration, multiple imputation for measurement error (MIME), and
      probabilistic sensitivity analysis (PSA), and provide guidance regarding the use
      of each method in scenarios likely to occur in practice. METHODS: This simulation
      experiment compared the performance of each method across different sample sizes,
      both differential and non-differential error, and differing levels of sensitivity
      and specificity of the exposure measure. RESULTS: Failure to adjust for
      measurement error led to substantial bias across all simulated scenarios ranging
      from a 35% to 208% change in the log-odds. For non-differential
      misclassification, regression calibration reduced this bias to between a 1% and
      23% change in the log-odds regardless of sample size. At higher sample sizes,
      MIME produced approximately unbiased (between a 0% and 9% change in the log-odds)
      and relatively efficient corrections for both non-differential and differential
      misclassification. PSA provided little utility for correcting misclassification
      due to the inefficiency of its estimates. CONCLUSION: Concern over measurement
      error resulting from self-reported adolescent alcohol use persists in research.
      Where appropriate, methods involving validity subsamples provide an efficient
      avenue for addressing these concerns.

PMID- 29451415
TI  - Clinical and Economic Impact of an Enhanced Recovery Pathway for Open and
      Laparoscopic Rectal Surgery.
AB  - BACKGROUND: The short-term benefits of laparoscopy for rectal surgery are
      equivocal. The objective of this study was to determine the clinical and economic
      impact of an enhanced recovery pathway (ERP) for laparoscopic and open rectal
      surgery. MATERIALS AND METHODS: All patients who underwent elective rectal
      resection with primary anastomosis between January 2009 and March 2012 at two
      tertiary-care, university-affiliated institutions were identified. Patients who
      met inclusion criteria were divided into four groups, according to surgical
      approach (laparoscopic [lap] or open) and perioperative management (ERP or
      conventional care [CC]). Length of stay (LOS), postoperative complications, and
      hospital costs were compared. RESULTS: A total of 381 patients were included in
      the analysis (201 open-CC, 34 lap-CC, 38 open-ERP, and 108 lap-ERP). Patients
      were mostly similar at baseline. ERPs significantly reduced median LOS after both
      open cases (open-CC 10 days versus open-ERP 7.5 days, P = .003) and laparoscopic
      cases (lap-CC 5 days versus lap-ERP 4.5 days, P = .046). ERPs also reduced
      variability in LOS compared with CC. There was no difference in postoperative
      complications with the use of ERPs (open-CC 51% versus open-ERP 50%, P = .419;
      lap-CC 32% versus lap-ERP 36%, P = .689). On multivariate analysis, both ERP (
      3.6 days [95% confidence interval, CI -6.0 to -1.3]) and laparoscopy (-3.6 days
      [95% CI -5.9 to -1.0]) were independently associated with decreased LOS. Overall
      costs were only lower when lap-ERP was compared with open-CC (mean difference 
      2420 CAN$ [95% CI -5628 to -786]). CONCLUSIONS: ERPs reduced LOS after rectal
      resections, and the combination of laparoscopy and ERPs significantly reduced
      overall costs compared to when neither strategy was used.

PMID- 29451416
TI  - Refinement of in vivo optical imaging: Development of a real-time respiration
      monitoring system.
AB  - In vivo optical imaging enables detection and quantification of light-emitting
      compounds from the whole body in small animals such as the mouse, but it
      typically requires the use of anaesthetics for subject immobilisation due to long
      exposure times. Excessively deep anaesthesia can result in unacceptably
      compromised physiology, whilst excessively light anaesthesia can result in
      animals waking up. Here we report a respiratory monitoring setup for an in vivo
      bioluminescence and fluorescence imaging device which simultaneously allows real
      time adaptive control of anaesthesia depth in multiple animals to (i) potentially
      increase the consistency between animals, (ii) ensure animals are maintained
      within minimally intrusive, adequate anaesthetic plane and (iii) provide a
      valuable refinement strategy for a common challenge within animal-based research.

PMID- 29451417
TI  - Coumestrol Confers Partial Resistance in Soybean Plants Against Cercospora Leaf
      Blight.
AB  - Although previous research showed that the purple symptom of Cercospora leaf
      blight (CLB) is associated with lower biomass of Cercospora cf. flagellaris and
      lower concentrations of cercosporin, a reactive oxygen species producer, as
      compared with blighted leaves, the hypothesis that the purple symptom is a plant
      reaction to the pathogen has never been tested. In this study, we demonstrated
      that high levels of coumestrol (COU) were associated with purple symptoms of CLB
      and that COU has strong antioxidant activity. Additionally, we found that COU is
      restricted to the pigmented areas of purple leaves, and the pigmentation is
      restricted to the adaxial surfaces, suggesting that COU may be acting as a
      sunscreen. Even though COU is associated with the purple leaf symptom, this
      coumestan is not the direct cause of discoloration in that COU is colorless.
      Quantification of chlorophyll a and b and total carotenoids suggested that
      blighted but not purple or asymptomatic leaves were undergoing photooxidative
      stress. Because the purple symptom is associated with high COU concentrations,
      lower biomass of C. cf. flagellaris, and lower cercosporin concentrations, we
      conclude that the purple symptom is a disease resistance reaction, mediated in
      part by COU, which provides a high level of antioxidant activity and, hence,
      partial resistance.

PMID- 29451418
TI  - Patient narratives in Yelp reviews offer insight into opioid experiences and the
      challenges of pain management.
AB  - AIM: To characterize Yelp reviews about pain management and opioids. METHODS: We
      manually coded and applied natural language processing to 836 Yelp reviews of US
      hospitals mentioning an opioid medication. RESULTS: Yelp reviews by patients and
      caregivers describing experiences with pain management and opioids had lower
      ratings compared with other reviews. Negative descriptions of pain management and
      opioid-related experiences were more commonly described than positive
      experiences, and the number of themes they reflected was more diverse.
      CONCLUSION: Yelp reviews offer insights into pain management and opioid use that
      are not assessed by traditional surveys. As a free, highly utilized source of
      unstructured narratives, Yelp may allow ongoing assessment of policies related to
      pain management and opioid use.

PMID- 29451419
TI  - Physical exercise, nutrition and hormones: three pillars to fight sarcopenia.
AB  - BACKGROUND: Sarcopenia is a pathophysiological condition diffused in elderly
      people; it represents a social issue due to the longer life expectancy and the
      growing aging population. It affects negatively quality of life and it represents
      a risk factor for other pathologies, such as diabetes, cardiovascular disease,
      and obesity. No silver bullet exists to hinder sarcopenia, but it may be
      counteracted by physical exercise, nutrition, and a proper endocrine milieu.
      Indeed, we aim to analyze the scientific literature to give to clinician
      effective advices to counteract sarcopenia. Main text: Physical exercise, proper
      nutrition, optimized hormonal homeostasis represent the three pillars to fight
      sarcopenia. Physical exercise represents the most effective remedy to face
      sarcopenia, in particular if it is combined with a proper diet and with an
      adequate endocrine milieu. Consistency in training, adequate daily protein intake
      and eugonadism seems to be the keys to fight sarcopenia. The combination of these
      three pillars might act synergistically. CONCLUSIONS: Optimization of these
      factors may increase their efficiency; however, scientific data may be sometimes
      confusing so far. Therefore, we aim to give practical advices to clinician to
      identify and to highlight the most important aspects in each of these three
      factors that should be addressed.

PMID- 29451420
TI  - Integration of clinical pharmacists into an ambulatory, pediatric
      hematology/oncology/transplant clinic.
AB  - Objectives To describe key activities performed by a newly deployed clinical
      pharmacist in an outpatient pediatric hematology, oncology, transplant clinic. To
      demonstrate how utilization of the pharmacist evolved, as indicated by changes in
      frequency of key activities, during the first four months of integration. Design
      Clinical pharmacists were made consistently available in an outpatient clinic
      serving hematology, oncology, transplant patients and their families. A list of
      key activities, based on provincial clinical pharmacist standards, was created to
      provide a framework for the role. Over a four-month period, the pharmacists
      recorded the number of times activities were performed. Results Over the data
      collection period, obtaining best possible medication histories (203), providing
      medication counseling (150), and creating adherence aids (144) were the most
      commonly performed activities. In comparison to the first month, key activities
      increased by 73% in the fourth month. Notably, providing recommendations for drug
      therapy (156%), assessments of adherence (122%), and best possible medication
      history collection (88%) increased considerably. Conclusions The integration of a
      pharmacist into an outpatient pediatric hematology, oncology, transplant clinic
      resulted in the provision of several key clinical pharmacy services. As the role
      developed, activities were performed more frequently, demonstrating growth in
      utilization of the pharmacist.

PMID- 29451421
TI  - Bionanocomposite scaffolds based on chitosan-gelatin and nanodimensional
      bioactive glass particles: In vitro properties and in vivo bone regeneration.
AB  - Bone repair bionanocomposite scaffolds were produced by incorporating dense
      bioactive glass nanoparticles or mesoporous bioactive glass nanospheres into a
      chitosan-gelatin polymer blend. The in vitro bioactivity of the scaffolds was
      assessed in simulated body fluid, and cell viability and osteogenic
      differentiation assays were performed with dental pulp stem cells. Bone
      regeneration properties of the scaffold materials were in vivo assessed by using
      a critical-sized femoral defect model in rat. The scaffold nanocomposites showed
      excellent cytocompatibility and ability to accelerate the crystallization of bone
      like apatite in vitro. Bionanocomposites prepared with bioactive glass
      nanoparticles were particularly more active to promote the osteogenic
      differentiation of dental pulp stem cells as judged by the higher activity of
      alkaline phosphatase. This result is attributed to the faster dissolution of
      bioactive glass nanoparticles into osteogenic ionic products compared to
      mesoporous bioactive glass nanospheres. In vivo experiments demonstrated that
      bioactive glass nanoparticles (5%)/chitosan-gelatin bionanocomposite
      significantly produces the highest amount of new bone (~80%) in the defect area
      after eight weeks of implantation. The bone regeneration capacity exhibited by
      the scaffolds formulated with nanodimensional bioactive glass particles make them
      attractive for bone reconstruction applications.

PMID- 29451422
TI  - Intraperitoneal Onlay Mesh Technique for Spigelian Hernia in an Outpatient and
      Short-Stay Surgery Unit: What's New in Intraperitoneal Meshes?
AB  - BACKGROUND: Spigelian hernia (SH) is a rare entity, but its surgical treatment is
      essential because of its high complication risk. Laparoscopic approaches have
      become the option in elective surgery because it has less morbidity and requires
      a shorter stay. Several laparoscopic techniques have been employed, but there is
      no gold standard technique for this kind of hernia. We report, in this study, our
      experience with intraperitoneal onlay mesh (IPOM) repair. MATERIALS AND METHODS:
      Fifteen patients underwent elective surgery for SH between 2008 and 2015 in a
      Short-Stay Surgical Unit. Laparoscopic IPOM technique was performed in all
      patients. The technique, epidemiological data, operative findings, hospital stay,
      morbidity, and follow-up are presented. RESULTS: Fifteen patients (8 males) with
      a median age of 57 years were operated on. They commonly presented an abdominal
      mass in the flank (73.3%). Computed tomography was necessary in 4 patients to
      complete preoperative diagnosis. The mean operating time was 43 minutes. No
      closure of the defect was associated and we employed expanded
      polytetrafluoroethylene-coated and polyvinylidene fluoride-coated polypropylene
      meshes. There were no postoperative complications and early discharge was
      possible in all cases. No recurrences or complications related to the mesh have
      been detected so far, with a median follow-up of 4 years (1-8). CONCLUSIONS: Our
      experience shows IPOM laparoscopic SH repair is a safe and effective technique
      with advantages that allow us to recommend it as the most advisable for SH
      treatment in Short-Stay Surgical Units. However, current controversies in the use
      of intraperitoneal meshes must be clarified.

PMID- 29451423
TI  - Replication of Type 2 diabetes-associated variants in a Saudi Arabian population.
AB  - Over 120 Type 2 diabetes (T2D) loci have been identified from genome-wide
      association studies (GWAS), mainly from Caucasian populations. Very limited
      knowledge is available on the Saudi Arabian population. In this study, 122
      previously reported T2D-related variants from 84 loci were examined in a Saudi
      Arabian cohort of 1,578 individuals (659 T2D cases and 919 controls). Eleven
      single nucleotide polymorphisms (SNPs) corresponding to nine independent loci had
      a P value <0.05. If a more stringent Bonferroni threshold of P = 4.1 * 10-4 ( =
      0.05/122) were applied, none of the SNPs would have reached the significance
      level. Nine of the SNPs with a P value <0.05 showed similar odds ratios as
      previously described, but rs11605924 ( CRY2) and rs9470794 ( ZFAND3) were in the
      opposite direction. This study demonstrates the importance of large-scale GWAS in
      the Saudi Arabian population to identify ethnicity-specific disease-associated
      variants.

PMID- 29451424
TI  - Risk Factors of Sexual Assault and Victimization Among Youth in Custody.
AB  - Research suggests that youth are at higher risk of sexual assault and
      victimization while in custody than adult inmates. However, compared with adult
      inmates, very little is known about the risk factors associated with such
      violence among youth in custody. Without sufficient research on risk factors
      associated with sexual assault and victimization among youth in custody,
      practitioners and policy makers may be reliant on the adult literature when
      making decisions about how to address and prevent such violence among juveniles.
      This article seeks to determine if extrapolating data from the substantial prison
      literature is appropriate by assessing the parallels between risk factors of
      sexual assault and victimization among youth in custody and those identified for
      adult inmates. This study uses data of 8,659 youth from the second administration
      of the National Survey of Youth in Custody (NSYC-2) to assess correlates of
      sexual assault and victimization during periods of detention. Study findings show
      that experiences with assault and victimization prior to the present period of
      detention were stronger indicators of sexual assault and victimization while in
      custody than youth characteristics and demographics and other experiences with
      assault and victimization. Further, there are differences in risk factors
      associated with sexual assault and victimization among youth in custody compared
      to adult inmates, which emphasizes the risk of prior sexual assault and
      victimization in the community and prior custodial settings.

PMID- 29451425
TI  - Biliary Tract-Infecting Myxosporeans from Estuarine and Reef Stonefish
      (Scorpaeniformes: Synanceiidae) Off Eastern Australia, with Descriptions of
      Sphaeromyxa horrida n. sp. and Myxidium lapipiscis n. sp. (Myxosporea:
      Bivalvulida).
AB  - Two new species of myxosporeans are described from the gallbladders of estuarine
      stonefish, Synanceia horrida, and reef stonefish, Synanceia verrucosa, from
      localities off Cairns, in tropical north Queensland and in Moreton Bay in
      southern Queensland, Australia. Sphaeromyxa horrida n. sp. can be distinguished
      from congeners in the morphologically distinct "balbianii" species group within
      Sphaeromyxa on the basis of morphometric differences in length and width of
      mature spores, length and width of polar capsules, and unique small-subunit (SSU)
      ribosomal (rDNA) sequence composition relative to other taxa. Replicate SSU rDNA
      sequences generated from Sph. horrida n. sp. collected from Sy. horrida and Sy.
      verrucosa in tropical north Queensland and from Sy. horrida in Moreton Bay were
      identical, suggesting that this species is widely distributed along the east
      coast of Australia. Myxidium lapipiscis n. sp. can be distinguished from the
      majority of described Myxidium species on the basis of its relatively small
      mature spore size (6.1-7.9 MUm long * 3.1-3.9 MUm wide), and its unique SSU rDNA
      sequence. Specimens putatively identified as M. lapipiscis n. sp. were found in
      Sy. horrida from both tropical north Queensland and Moreton Bay, suggesting that
      this taxon is also widely distributed along the east coast of Australia. However,
      no molecular data were available for the specimens from tropical north Queensland
      for comparative genetic analyses. Bayesian inference and maximum likelihood
      analysis of the SSU rDNA sequences for these 2 new species revealed that Sph.
      horrida n. sp. formed a strongly supported clade with Sphaeromyxa zaharoni
      Diamant, Whipps, and Kent, 2004, which was described from the scorpaeniform,
      Pterois miles, from the Red Sea. This is the first report of myxozoans infecting
      stonefish (Synanceiidae).

PMID- 29451426
TI  - Prioritizing pediatric chronic pain and comprehensive pain treatment in the
      context of the opioid epidemic.

PMID- 29451427
TI  - Easier Seen Than Done: Merely Watching Others Perform Can Foster an Illusion of
      Skill Acquisition.
AB  - Modern technologies such as YouTube afford unprecedented access to the skilled
      performances of other people. Six experiments ( N = 2,225) reveal that repeatedly
      watching others can foster an illusion of skill acquisition. The more people
      merely watch others perform (without actually practicing themselves), the more
      they nonetheless believe they could perform the skill, too (Experiment 1).
      However, people's actual abilities-from throwing darts and doing the moonwalk to
      playing an online game-do not improve after merely watching others, despite
      predictions to the contrary (Experiments 2-4). What do viewers see that makes
      them think they are learning? We found that extensive viewing allows people to
      track what steps to take (Experiment 5) but not how those steps feel when taking
      them. Accordingly, experiencing a "taste" of performing attenuates the illusion:
      Watching others juggle but then holding the pins oneself tempers perceived change
      in one's own ability (Experiment 6). These findings highlight unforeseen problems
      for self-assessment when watching other people.

PMID- 29451428
TI  - Extended-Spectrum beta-Lactamase, AmpC, and MBL-Producing Gram-Negative Bacteria
      on Fresh Vegetables and Ready-to-Eat Salads Sold in Local Markets.
AB  - We investigated the occurrence of extended-spectrum beta-lactamase (ESBL), AmpC,
      and carbapenemase-producing Gram-negative bacteria isolated from 160 samples of
      fresh vegetables (n = 80) and ready-to-eat (RTE) prepacked salads (n = 80).
      Phenotypic and genotypic analyses were carried out on the isolates in terms of
      the species present and relative resistance. Resistance to beta-lactam
      antibiotics was found in only 44 (24 from fresh vegetables and 20 from RTE
      salads) of a total of 312 Gram-negative strains (14.1%). The prevalence of ESBL
      producing strains from fresh vegetables was 83.3% (20/24) and 16.7% (4/24) for
      AmpC. Among the 20 bacterial isolates from RTE salads, 80% (16/20) were
      identified as ESBL-producing strains and the remaining 20% (4/20) as MBL
      producing strains. PCR and sequencing confirmed the presence of blaSHV-12, blaCTX
      M-1, blaCTX-M-15, blaRHAN-1, blaACC-1, blaDHA-1, blaVIM-1, and blaIMP-1. Seven
      different replicons were identified, where IncHI1, FIA, and I1 were the most
      representative types; when compared with the Inc types, isolates from fresh
      vegetables and RTE salads were similar. The location of genes on a conjugative
      plasmid was confirmed by positive results obtained with conjugation assays. Our
      study has demonstrated the occurrence and distribution of ESBL/AmpC and MBL
      strains in fresh vegetables and RTE salads in Italy and possible public health
      risks associated with consumption of these fresh products.

PMID- 29451430
TI  - How Can Researchers Tell Whether Someone Has a False Memory? Coding Strategies in
      Autobiographical False-Memory Research: A Reply to Wade, Garry, and Pezdek
      (2018).

PMID- 29451429
TI  - Perceived injustice in chronic pain: an examination through the lens of
      predictive processing.
AB  - Chronic pain conditions have been shown to be exacerbated by psychological
      factors, and a better understanding of these factors can inform clinical practice
      and improve the efficacy of interventions. The current paper investigates
      perceived injustice, a novel psychosocial construct, within a framework
      influenced by the tenets of predictive processing. The proposed conceptual model
      derived from tenets of predictive processing yields a single hierarchical self
      reconfiguring system driven by prediction, which accounts for a wide range of
      human experiences such as perception, behavior, learning and emotion. This
      conceptualization can inform the development and implementation of more targeted
      therapeutic interventions for chronic pain.

PMID- 29451431
TI  - Study protocol of hypoalgesic effects of low frequency and burst-modulated
      alternating currents on healthy individuals.
AB  - : The aim of the study will be to compare different types of analgesic electrical
      currents in relation to the pressure pain threshold and sensory comfort in
      healthy individuals. A total of 100 individuals will be randomly assigned to four
      groups: transcutaneous electrical nerve stimulation, interferential current,
      Aussie current or placebo. The electrical stimulation will be administered with a
      strong level for 30 min and to the placebo group, the electrodes will be
      positioned while the equipment will remain switched off. The pressure pain
      threshold and sensory comfort will be measured with an algometer and the visual
      analogue scale, respectively. The level of significance will be p < 0.05. STUDY
      REGISTRATION: NCT01950728 (clinical trials).

PMID- 29451432
TI  - Diagnosing isolated hepatosplenic tuberculosis in an immunocompetent patient: a
      case report.
AB  - For many years, tuberculosis (TB) has been endemic in Pakistan; many rare and
      unusual presentations have been reported. There is a myriad of non-specific
      symptoms which always requires a high index of clinical suspicion for TB. World
      Health Organization data suggest that Pakistan ranks as the fifth highest country
      burdened with TB and has the fourth highest prevalence of multi-drug resistant TB
      globally. With an annual incidence of 277 cases per 100,000, the importance of
      early diagnosis and treatment is self-evident. We present a case where a strong
      suspicion of isolated hepatosplenic TB in an immunocompetent patient justified a
      directed approach.

PMID- 29451433
TI  - Populations of Phytophthora rubi Show Little Differentiation and High Rates of
      Migration Among States in the Western United States.
AB  - Population genetics is a powerful tool to understand patterns and evolutionary
      processes that are involved in plant-pathogen emergence and adaptation to
      agricultural ecosystems. We are interested in studying the population dynamics of
      Phytophthora rubi, the causal agent of Phytophthora root rot in raspberry. P.
      rubi is found in the western United States, where most of the fresh and processed
      raspberries are produced. We used genotyping-by-sequencing to characterize
      genetic diversity in populations of P. rubi sampled in the United States and
      other countries. Our results confirm that P. rubi is a monophyletic species with
      complete lineage sorting from its sister taxon P. fragariae. Overall, populations
      of P. rubi show low genetic diversity across the western United States.
      Demographic analyses suggest that populations of P. rubi from the western United
      States are the source of pathogen migration to Europe. We found no evidence for
      population differentiation at a global or regional (western United States) level.
      Finally, our results provide evidence of migration from California and Oregon
      into Washington. This report provides new insights into the evolution and
      structure of global and western United States populations of the raspberry
      pathogen P. rubi, indicating that human activity might be involved in moving the
      pathogen among regions and fields.

PMID- 29451434
TI  - The ELR-SOBIR1 Complex Functions as a Two-Component Receptor-Like Kinase to Mount
      Defense Against Phytophthora infestans.
AB  - The ELICITIN RESPONSE protein (ELR) from Solanum microdontum can recognize INF1
      elicitin of Phytophthora infestans and trigger defense responses. ELR is a
      receptor-like protein (RLP) that lacks a cytoplasmic signaling domain and is
      anticipated to require interaction with a signaling-competent receptor-like
      kinase. SUPPRESSOR OF BIR1-1 (SOBIR1) has been proposed as a general interactor
      for RLPs involved in immunity and, as such, is a potential interactor for ELR.
      Here, we investigate whether SOBIR1 is required for response to INF1 and
      resistance to P. infestans and whether it associates with ELR. Our results show
      that virus-induced gene silencing of SOBIR1 in Nicotiana benthamiana leads to
      loss of INF1-triggered cell death and increased susceptibility to P. infestans.
      Using genetic complementation, we found that the kinase activity of SOBIR1 is
      required for INF1-triggered cell death. Coimmunoprecipitation experiments showed
      that ELR constitutively associates with potato SOBIR1 in planta, forming a
      bipartite receptor complex. Upon INF1 elicitation, this ELR-SOBIR1 complex
      recruits SERK3 (SOMATIC EMBRYOGENESIS RECEPTOR KINASE 3) leading to downstream
      signaling activation. Overall, our study shows that SOBIR1 is required for basal
      resistance to P. infestans and for INF1-triggered cell death and functions as an
      adaptor kinase for ELR.

PMID- 29451435
TI  - Safe insertion of S-2 alar iliac screws: radiological comparison between 2
      insertion points using computed tomography and 3D analysis software.
AB  - OBJECTIVE S-2 alar iliac (S2AI) screws are commonly used as anchors for
      lumbosacral fixation. A serious potential complication of screw insertion is
      major vascular injury due to anterior or caudal screw deviation. To avoid screw
      deviation, the pelvic inlet view on intraoperative fluoroscopy images is
      recommended. However, there has been no detailed investigation of optimal
      fluoroscopic incline with the pelvic inlet view. The purpose of this study was to
      investigate the safety margins and to optimize fluoroscopic settings to avoid
      screw deviation with 2 reported insertion techniques using 3D analysis software
      and CT. METHODS The study included 50 patients (25 men and 25 women) who
      underwent abdominal-pelvic CT. With the use of software, the ideal S2AI screws
      were set from 2 entry points: A) the midpoint between the S-1 dorsal foramen and
      the S-2 dorsal foramen where they meet the lateral sacral crest, and B) 1 mm
      inferior and 1 mm lateral to the S-1 dorsal foramen. Anteriorly or caudally
      deviated screws were defined as deviation of a half thread of the ideal screw by
      rotation anteriorly or caudally from the entry point. The angular safety margins
      were compared between the 2 entry points, and patients with small safety margins
      were investigated. Subsequently, fluoroscopic images were virtualized on ray sum
      rendered images. Conditions that provided proper recognition of screw deviation
      were investigated via lateral and anteroposterior views with the beam tilted
      caudally. RESULTS The safety margins of S2AI screws were smaller in the anterior
      direction than in the caudal direction and by entry point A than by entry point B
      (A: 9.1 degrees  +/- 1.6 degrees  and B: 9.7 degrees  +/- 1.5 degrees  in the
      anterior direction; A: 10.9 degrees  +/- 3.8 degrees  and B: 13.9 degrees  +/-
      4.1 degrees  in the caudal direction). In contrast, patients with a deep-seated L
      5 vertebral body tended to have smaller safety margins in the caudal direction.
      All anteriorly deviated screws were recognized with a 60 degrees -70 degrees 
      inlet view from the S-1 slope. The caudally deviated screws were all recognized
      on the lateral view, but 31% of screws at entry point A and 21% of screws at
      entry point B were not recognized on the pelvic inlet view. CONCLUSIONS S2AI
      screws should be carefully placed to avoid anterior deviation compared with
      caudal deviation in terms of the safety margin, except in patients with a deep
      seated L-5. The difference in safety margins between entry points A and B was
      negligible. Intraoperative fluoroscopy is recommended with a pelvic inlet view
      tilted 60 degrees -70 degrees  from the S-1 slope to avoid anterior screw
      deviation. The lateral view is recommended to confirm that the screw is not
      deviated caudally.

PMID- 29451436
TI  - Novel posterior artificial atlanto-odontoid joint for atlantoaxial instability: a
      biomechanical study.
AB  - OBJECTIVE Atlantoaxial instability is usually corrected by anterior and/or
      posterior C1-2 fusion. However, fusion can lead to considerable loss of movement
      at the C1-2 level, which can adversely impact a patient's quality of life. In
      this study, the authors investigated the stability and function of a novel
      posterior artificial atlanto-odontoid joint (NPAAJ) by using cadaveric cervical
      spines. METHODS The Oc-C7 regions from 10 cadaveric spines were used for
      anteroposterior (AP) translation and range of motion (ROM) tests while intact and
      after destabilization, NPAAJ implantation, and double-rod fixation. RESULTS The
      mean AP C1-2 translational distances in the intact, destabilization, and double
      rod groups were 6.53 +/- 1.07 mm, 11.54 +/- 1.59 mm, and 3.24 +/- 0.99 mm,
      respectively, and the AP translational distance in the NPAAJ group was
      significantly different from that in the intact group (p < 0.05). The AP
      translational distance in the NPAAJ group was not significantly different from
      that in the double-rod group (p = 0.24). The mean flexion, extension, and axial
      rotation ROM values of the NPAAJ group were 9.87 degrees  +/- 0.91 degrees , 8.75
      degrees  +/- 0.99 degrees , and 61.93 degrees  +/- 2.93 degrees , respectively,
      and these were lower than the corresponding values in the intact group (p <
      0.05). The mean lateral bending ROM in the NPAAJ group (9.26 degrees  +/- 0.86
      degrees ) was not significantly different from that in the intact group (p =
      0.23), and the flexion, extension, and rotation ranges in the NPAAJ group were
      79.5%, 85.2%, and 82.3%, respectively, of those in the intact group. CONCLUSIONS
      Use of NPAAJ for correction of atlantoaxial instability disorders caused by
      congenital odontoid dysplasia, odontoid fracture nonunion, and C-1 transverse
      ligament disruption (IA, IB, and IIB) may restore the stability and preserve most
      of the ROM of C1-2. Additionally, the NPAAJ may prevent soft tissue from
      embedding within the joint. However, additional studies should be performed
      before the NPAAJ is used clinically.

PMID- 29451437
TI  - Do intraoperative radiographs predict final lumbar sagittal alignment following
      single-level transforaminal lumbar interbody fusion?
AB  - OBJECTIVE The study aimed to determine if the intraoperative segmental lordosis
      (as calculated on a cross-table lateral radiograph following a single-level
      transforaminal lumbar interbody fusion [TLIF] for degenerative
      spondylolisthesis/low-grade isthmic spondylolisthesis) is maintained at discharge
      and at 6 months postsurgery. METHODS The authors reviewed images and medical
      records of patients >= 16 years of age with a diagnosis of an isolated single
      level, low-grade spondylolisthesis (degenerative or isthmic) with symptomatic
      spinal stenosis treated between January 2008 and April 2014. Age, sex, surgical
      level, surgical approach, and facetectomy (unilateral vs bilateral) were
      recorded. Upright standardized preoperative, early, and 6-month postoperative
      radiographs, as well as intraoperative lateral radiographs, were analyzed for the
      pelvic incidence, segmental lumbar lordosis (SLL) at the TILF level, and total LL
      (TLL). In addition, the anteroposterior position of the cage in the disc space
      was documented. Data are presented as the mean +/- SD; a p value < 0.05 was
      considered significant. RESULTS Eighty-four patients were included in the study.
      The mean age of patients was 56.8 +/- 13.7 years, and 46 patients (55%) were men.
      The mean pelvic incidence was 59.7 degrees  +/- 11.9 degrees , and a posterior
      midline approach was used in 47 cases (56%). All TLIF procedures were single
      level using a bullet-shaped cage. A bilateral facetectomy was performed in 17
      patients (20.2%), and 89.3% of procedures were done at the L4-5 and L5-S1
      segments. SLL significantly improved intraoperatively from 15.8 degrees  +/- 7.5
      degrees  to 20.9 degrees  +/- 7.7 degrees , but the correction was lost after
      ambulation. Compared with preoperative values, at 6 months the change in SLL was
      modest at 1.8 degrees  +/- 6.7 degrees  (p = 0.025), whereas TLL increased by 4.3
      degrees  +/- 9.6 degrees  (p < 0.001). The anteroposterior position of the cage,
      approach, level of surgery, and use of a bilateral facetectomy did not
      significantly affect postoperative LL. CONCLUSIONS Following a single-level TLIF
      procedure using a bullet-shaped cage, the intraoperative improvement in SLL is
      largely lost after ambulation. The improvement in TLL over time is probably due
      to the decompression part of the procedure. The approach, level of surgery,
      bilateral facetectomy, and position of the cage do not seem to have a significant
      effect on LL achieved postoperatively.

PMID- 29451439
TI  - Editorial. Dynamic atlantoaxial instrumentation to preserve cervical mobility.

PMID- 29451438
TI  - Reinnervation of the rectum with transfer of the genital branch of the
      genitofemoral nerve to the pelvic nerve in rats.
AB  - OBJECTIVE The purpose of this study was to determine the feasibility of rectum
      reinnervation with transfer of a primarily genitofemoral nerve to the pelvic
      nerve in the rat. METHODS Thirty-six male rats were randomly divided into 3
      groups: rats in the nerve transfer group (n = 12) were subjected to rectal
      denervation and then bilateral genitofemoral nerve-pelvic nerve transfer; rats in
      the nerve resection group (n = 12) underwent rectum denervation without nerve
      transfer; and rats in the control group (n = 12) underwent sham surgery. Rectum
      denervation was achieved by transection of the L-6 spinal nerves, the spinal
      nerves below L-6, and the pelvic nerve. Four months postoperatively, retrograde
      nerve tracing, regenerative nerve morphological examination, and rectal manometry
      assessment were performed. RESULTS Regenerative nerve morphological examination
      showed good axonal regeneration after genitofemoral nerve transfer. Nerve
      stimulation induced increased rectal pressures in 10 of 12 rats in the nerve
      transfer group. The mean rectal pressure in this group was 54.9 +/- 7.1 mm Hg,
      which is higher than the mean value in the nerve resection group (5.5 +/- 2.0 mm
      Hg) but lower than that in the control group (70.6 +/- 8.5 mm Hg) (p < 0.05). The
      appearance of FluoroGold-labeled neurons in the L-1 and L-2 spinal cord segments
      in the nerve transfer group confirmed the formation of new neural pathways.
      CONCLUSIONS The results have demonstrated that genitofemoral nerve-pelvic nerve
      transfer can achieve nerve regeneration. In this animal model, the authors were
      able to reinnervate the rectum by nerve transfer.

PMID- 29451441
TI  - MSJ 2018-editorial comment.

PMID- 29451440
TI  - Radiologically isolated syndrome or subclinical multiple sclerosis: MAGNIMS
      consensus recommendations.

PMID- 29451442
TI  - 2017 McDonald MS diagnostic criteria: Evidence-based revisions.

PMID- 29451443
TI  - Retrospective study of 152 feline cytological bone marrow examinations:
      preliminary classification and ranges.
AB  - OBJECTIVES: Cytological assessment of the bone marrow is an essential tool for
      understanding and investigating haematological abnormalities. Sometimes it
      represents the only way to reach a definitive diagnosis. The purpose of this
      study was to provide a general overview regarding the prevalence of feline bone
      marrow disorders encountered in a private European laboratory setting, to
      classify them and to assess the differential cell counts related to such
      disorders. METHODS: In total, 152 bone marrow samples were classified using
      cytological and numerical criteria. The bone marrow cytological examinations were
      performed after the identification of haematological alterations, such as
      cytopenias, increased number of cells or suspicion of malignant blood disorders.
      RESULTS: Of the 152 bone marrow samples evaluated, 71 (46.7%) were classified as
      hyperplastic, primarily granulocytic and erythroid hyperplasia (50.7% and 45.1%,
      respectively, of the total hyperplasia); 23 (15.1%) showed dysmyelopoiesis,
      mainly in the form of myelodysplastic syndrome (39.1% of the total
      dysmyelopoiesis); 21 (13.8%) had no cytological abnormalities; 17 (11.2%) were
      malignant blood disorders; 15 (9.9%) had hypoplastic conditions; and two (1.3%)
      were miscellaneous diseases. Metastatic disease was detected in only two cases
      (1.3%). Differential cell counts and myeloid-to-erythroid (M:E) ratios were
      reported for normal, erythroid hypoplastic, erythroid and granulocytic
      hyperplastic and dysplastic conditions. CONCLUSIONS AND RELEVANCE: This study
      provides a general overview of the prevalence and incidence of feline bone marrow
      disorders together with ranges for differential nucleated cell counts and M:E
      ratios for the various conditions reported.

PMID- 29451444
TI  - Survival and prognostic factors in cats with restrictive cardiomyopathy: a review
      of 90 cases.
AB  - OBJECTIVES: Large studies focusing on restrictive cardiomyopathy (RCM) in the cat
      are scarce. The aims of this retrospective study were to describe epidemiological
      characteristics and to analyse prognostic factors affecting survival in cats with
      RCM. METHODS: The clinical archives of the Gran Sasso Veterinary Clinic (Milan,
      Italy) and of the cardiology unit of the Department of Veterinary Medicine
      (University of Milan, Italy) from 1997-2015 were reviewed for all cats diagnosed
      with RCM based on an echocardiographic examination (left atrial/biatrial
      enlargement, normal left ventricle wall thickness, normal or mildly decreased
      systolic function and restrictive left ventricle filling pattern with pulsed
      Doppler echocardiography). RESULTS: The study population comprised 90 cats (53
      male, 37 female) with an echocardiographic diagnosis of RCM. Most were domestic
      shorthairs (n = 60) with a mean +/- SD age of 10.0 +/- 4.3 years and a median
      weight of 3.8 kg (interquartile range 3.2-5 kg). Most cats were symptomatic (n =
      87). The most common clinical sign was respiratory distress (n = 75). Follow-up
      was available for 60 cats and the median survival time (MST) was 69 days (95%
      confidence interval [CI] 0-175 days). Cardiac-related death occurred in 50 cats.
      In the multivariate Cox analysis only respiratory distress showed a statistically
      significant effect on survival. The cats without respiratory distress showed an
      MST of 466 days (95% CI 0-1208); cats with respiratory distress showing an MST of
      64 days (95% CI 8-120; P = 0.011). CONCLUSIONS AND RELEVANCE: RCM can be
      considered an end-stage condition associated with a poor prognosis, with few cats
      not showing clinical signs and surviving >1 year. Most cats died of cardiac
      disease within a very short time.

PMID- 29451445
TI  - Repeated measurements of renal function in evaluating its decline in cats.
AB  - OBJECTIVES: The aim of this study was to describe the variability in renal
      function markers in non-azotaemic and azotaemic cats, and also the rate of change
      in the markers. METHODS: Plasma creatinine concentration and its reciprocal,
      glomerular filtration rate (GFR) and urine specific gravity (USG) were studied as
      markers of renal function in client-owned cats. GFR was determined using a
      corrected slope-intercept iohexol clearance method. Renal function testing was
      performed at baseline and a second time point. The within-population variability
      (coefficient of variation; CV%) was determined at the baseline time point. Within
      individual variability (CV%) and rate of change over time were determined from
      the repeated measurements. RESULTS: Twenty-nine cats were included in the study,
      of which five had azotaemic chronic kidney disease. The within-individual
      variability (CV%) in creatinine concentration was lower in azotaemic cats than in
      non-azotaemic cats (6.81% vs 8.82%), whereas the within-individual variability in
      GFR was higher in azotaemic cats (28.94% vs 19.98%). The within-population
      variability was greatest for USG (67.86% in azotaemic cats and 38.00% in non
      azotaemic cats). There was a negative rate of change in creatinine concentration
      in azotaemic and non-azotaemic cats (-0.0265 and -0.0344 umol/l/day,
      respectively) and a positive rate of change of GFR in azotaemic and non-azotaemic
      cats (0.0062 and 0.0028 ml/min/day, respectively). CONCLUSIONS AND RELEVANCE: The
      within-individual variability data suggest creatinine concentration to be the
      more useful marker for serial monitoring of renal function in azotaemic cats. In
      contrast, in non-azotaemic cats, GFR is a more useful marker for serial
      monitoring of renal function. The majority of cats with azotaemic CKD did not
      have an appreciable decline in renal function during the study.

PMID- 29451446
TI  - Improving patient safety during introduction of novel medical devices through
      cumulative summation analysis.
AB  - OBJECTIVE The aim of this study was to implement cumulative summation (CUSUM)
      analysis as an early-warning detection and quality assurance system for
      preclinical testing of the iSYS1 novel robotic trajectory guidance system.
      METHODS Anatomically accurate 3D-printed skull phantoms were created for 3
      patients who underwent implantation of 21 stereoelectroencephalography electrodes
      by surgeons using the current standard of care (frameless technique).
      Implantation schema were recreated using the iSYS1 system, and paired accuracy
      measures were compared with the previous frameless implantations. Entry point,
      target point, and implantation angle accuracy were measured on postimplantation
      CT scans. CUSUM analysis was undertaken prospectively. RESULTS The iSYS1
      trajectory guidance system significantly improved electrode entry point
      accuracies from 1.90 +/- 0.96 mm (mean +/- SD) to 0.76 +/- 0.57 mm (mean +/- SD)
      without increasing implantation risk. CUSUM analysis was successful as a
      continuous measure of surgical performance and acted as an early-warning
      detection system. The surgical learning curve, although minimal, showed
      improvement after insertion of the eighth electrode. CONCLUSIONS The iSYS1
      trajectory guidance system did not show any increased risk during phantom
      preclinical testing when used by neurosurgeons who had no experience with its
      use. CUSUM analysis is a simple technique that can be applied to all stages of
      the IDEAL (idea, development, exploration, assessment) framework as an extra
      patient safety mechanism. Further clinical trials are required to prove the
      efficacy of the device.

PMID- 29451447
TI  - Peripheral nerve grafts implanted into the substantia nigra in patients with
      Parkinson's disease during deep brain stimulation surgery: 1-year follow-up study
      of safety, feasibility, and clinical outcome.
AB  - OBJECTIVE Currently, there is no treatment that slows or halts the progression of
      Parkinson's disease. Delivery of various neurotrophic factors to restore
      dopaminergic function has become a focus of study in an effort to fill this unmet
      need for patients with Parkinson's disease. Schwann cells provide a readily
      available source of such factors. This study presents a 12-month evaluation of
      safety and feasibility, as well as the clinical response, of implanting
      autologous peripheral nerve grafts into the substantia nigra of patients with
      Parkinson's disease at the time of deep brain stimulation (DBS) surgery. METHODS
      Standard DBS surgery targeting the subthalamic nucleus was performed in 8 study
      participants. After DBS lead implantation, a section of the sural nerve
      containing Schwann cells was harvested and unilaterally grafted to the substantia
      nigra. Adverse events were continually monitored. Baseline clinical data were
      obtained during standard preoperative evaluations. Clinical outcome data were
      obtained with postoperative clinical evaluations, neuropsychological testing, and
      MRI at 1 year after surgery. RESULTS All 8 participants were implanted with DBS
      systems and grafts. Adverse event profiles were comparable to those of standard
      DBS surgery with the exception of 1 superficial infection at the sural nerve
      harvest site. Three participants also reported numbness in the distribution of
      the sural nerve distal to the harvest site. Motor scores on Unified Parkinson's
      Disease Rating Scale (UPDRS) part III while the participant was off therapy at 12
      months improved from baseline (mean +/- SD 25.1 +/- 15.9 points at 12 months vs
      32.5 +/- 9.7 points at baseline). An analysis of the lateralized UPDRS scores
      also showed a greater overall reduction in scores on the side contralateral to
      the graft. CONCLUSIONS Peripheral nerve graft delivery to the substantia nigra at
      the time of DBS surgery is feasible and safe based on the results of this initial
      pilot study. Clinical outcome data from this phase I trial suggests that grafting
      may have some clinical benefit and certainly warrants further study to determine
      if this is an efficacious and neurorestorative therapy. Clinical trial
      registration no.: NCT01833364 (clinicaltrials.gov).

PMID- 29451448
TI  - Donor nerve axotomy and axonal regeneration after end-to-side neurorrhaphy in a
      rodent model.
AB  - OBJECTIVE In this study, the authors used a surgical model of end-to-side
      neurorrhaphy between a nerve graft and a donor tibial nerve in adult rats to
      investigate the optimal conditions for axonal regeneration induced by the donor
      nerve. They also assessed the importance of a more favorable pathway using a
      predegenerated nerve graft to attract regenerating axons to regrow into the graft
      and then directing and improving their growth toward the target in comparison
      with results obtained with a fresh nerve graft. METHODS End-to-side neurorrhaphy
      was performed between a nerve graft and a donor tibial nerve. The nerve graft was
      obtained from the left tibial nerve, which was either freshly removed or
      predegenerated 1 week prior to neurorrhaphy. The donor right tibial nerve was
      injured by epineurium removal alone, injured by epineurium removal with cross
      section of 20% or 50% of the total axons at the coaptation site, or left intact.
      The animals were followed postoperatively for a 6-week period, and outcomes were
      evaluated by optical microscopy and retrograde labeling to detect the regenerated
      primary sensory neurons located in the lumbar dorsal root ganglia and spinal
      motor neurons located in the lumbar spinal ventral horn. RESULTS At the end of
      the follow-up period, no regenerating axons were observed in the nerve grafts
      when the donor nerve was left intact, and very few axons were detected when the
      donor nerve was injured by epineurium removal alone. However, numerous
      regenerating axons appeared in the grafts when the donor nerve was axotomized,
      and the greatest number was achieved with a 50% cross section axotomized nerve.
      In the rats with a 50% cross section of the donor nerve, better nerve-like
      morphology of the grafts was observed, without connective adhesions. When a
      predegenerated nerve graft was used, more regenerating axons were attracted and
      elongated with a more regular shape and improved myelination. CONCLUSIONS Axonal
      regrowth into a nerve graft depends on axotomy of the donor nerve after end-to
      side neurorrhaphy. More efficient attraction and an improved structure of the
      regenerating axons were achieved when a predegenerated nerve graft was used.
      Furthermore, a nerve graft may require a certain number of regenerating axons to
      maintain a nerve-like morphology.

PMID- 29451449
TI  - Letter to the Editor. The efficacy of local vancomycin for reducing surgical site
      infections after cranioplasty.

PMID- 29451450
TI  - Obituary. Walter Eugene Stern, MD, 1920-2017.

PMID- 29451451
TI  - Critical assessment of pediatric neurosurgery patient/parent educational
      information obtained via the Internet.
AB  - OBJECTIVE The Internet is used frequently by patients and family members to
      acquire information about pediatric neurosurgical conditions. The sources,
      nature, accuracy, and usefulness of this information have not been examined
      recently. The authors analyzed the results from searches of 10 common pediatric
      neurosurgical terms using a novel scoring test to assess the value of the
      educational information obtained. METHODS Google and Bing searches were performed
      for 10 common pediatric neurosurgical topics (concussion, craniosynostosis,
      hydrocephalus, pediatric brain tumor, pediatric Chiari malformation, pediatric
      epilepsy surgery, pediatric neurosurgery, plagiocephaly, spina bifida, and
      tethered spinal cord). The first 10 "hits" obtained with each search engine were
      analyzed using the Currency, Relevance, Authority, Accuracy, and Purpose (CRAAP)
      test, which assigns a numerical score in each of 5 domains. Agreement between
      results was assessed for 1) concurrent searches with Google and Bing; 2) Google
      searches over time (6 months apart); 3) Google searches using mobile and PC
      platforms concurrently; and 4) searches using privacy settings. Readability was
      assessed with an online analytical tool. RESULTS Google and Bing searches yielded
      information with similar CRAAP scores (mean 72% and 75%, respectively), but with
      frequently differing results (58% concordance/matching results). There was a high
      level of agreement (72% concordance) over time for Google searches and also
      between searches using general and privacy settings (92% concordance). Government
      sources scored the best in both CRAAP score and readability. Hospitals and
      universities were the most prevalent sources, but these sources had the lowest
      CRAAP scores, due in part to an abundance of self-marketing. The CRAAP scores for
      mobile and desktop platforms did not differ significantly (p = 0.49). CONCLUSIONS
      Google and Bing searches yielded useful educational information, using either
      mobile or PC platforms. Most information was relevant and accurate; however, the
      depth and breadth of information was variable. Search results over a 6-month
      period were moderately stable. Pediatric neurosurgery practices and neurosurgical
      professional organization websites were inferior (less current, less accurate,
      less authoritative, and less purposeful) to governmental and encyclopedia-type
      resources such as Wikipedia. This presents an opportunity for pediatric
      neurosurgeons to participate in the creation of better online patient/parent
      educational material.

PMID- 29451452
TI  - Epidemiology of spinal injury in childhood and adolescence in the United States:
      1997-2012.
AB  - OBJECTIVE There has been no successful study of trends in population-based
      incidences of pediatric spinal injury in the United States. The goal of the
      current study was to develop robust data to correct this deficiency in
      contemporary trauma epidemiology. METHODS Discharges coded for spinal injury were
      extracted from the Kids' Inpatient Database for 1997, 2000, 2003, 2006, 2009, and
      2012 for patients younger than 18 years. Childhood was defined as ages 0 through
      14 years and adolescence as ages 15, 16, and 17 years. Denominator population
      data were taken from the website of the US Census. Annual incidences were
      estimated for hospitalization for spinal injury, spinal cord injury (SCI), and
      hospital death with spinal injury. Mechanistic and anatomical patterns of injury
      were studied. RESULTS The annual population-based incidences of hospitalization
      for spinal injury, SCI, and death with spinal injury trended downward from 1997
      to 2012 for children and adolescents in the United States. Rates of SCI and death
      fell faster than overall hospitalization rates, suggesting lower thresholds for
      admission or greater diagnostic sensitivity to minor injuries over time. The
      incidence of hospitalization for spinal injury was roughly 8 times greater for
      adolescents than for children, and the incidence of SCI was roughly 6 times
      greater. Motor vehicle crash predominated among mechanisms for both children and
      adolescents, but penetrating injuries and sport injuries were more commonly
      associated with SCI. Lumbosacral injuries predominated in both children and
      adolescents, but injuries of the cervical spine were more commonly associated
      with SCI. CONCLUSIONS Further research is needed to identify the cause or causes
      of the observed decline in injury rates. Epidemiological data can inform and
      support prevention efforts.

PMID- 29451453
TI  - Trapped ventricle after laser ablation of a subependymal giant cell astrocytoma
      complicated by intraventricular gadolinium extravasation: case report.
AB  - Magnetic resonance imaging-guided stereotactic laser ablation of intracranial
      targets, including brain tumors, has expanded dramatically over the past decade,
      but there have been few reports of complications, especially those occurring in a
      delayed fashion. Laser ablation of subependymal giant cell astrocytomas (SEGAs)
      is an attractive alternative to maintenance immunotherapy in some children with
      tuberous sclerosis complex (TSC); however, the effect of treatment on disease
      progression and the nature and frequency of potential complications remains
      largely unknown. The authors report the case of a 5-year-old boy with TSC who
      underwent stereotactic laser ablation of a SEGA at the right foramen of Monro on
      2 separate occasions. After the second ablation, immediate posttreatment MRI
      revealed gadolinium extravasation from the tumor into the lateral ventricle. Nine
      months later, the patient presented with papilledema and delayed obstructive
      hydrocephalus secondary to intraventricular adhesions causing a trapped right
      lateral ventricle. This was successfully treated with endoscopic septostomy. The
      authors discuss the potential cause and clinical management of a delayed
      complication not previously reported after a relatively novel surgical therapy.

PMID- 29451454
TI  - Efficacy of intraoperative ultrasonography in neurosurgical tumor resection.
AB  - OBJECTIVE Intraoperative ultrasonography (IOUS) is a widely accessible imaging
      modality that provides real-time surgical guidance with minimal identified risk
      or additional operative time. A recent study by the authors found a strong
      correlation between IOUS and postoperative MRI findings when evaluating the
      extent of tumor resection, suggesting that IOUS might have significant clinical
      implications. The objective of this study was to expand on results from the
      previous study in order to provide more evidence on the usage of IOUS in the
      determination of gross-total resection (GTR) in both adult and pediatric patients
      with brain tumors. METHODS This study consisted of a retrospective review of
      adult and pediatric neurosurgical patients who were treated at Albany Medical
      Center between August 2009 and March 2016 for a tumor of the brain. All patients
      were treated with IOUS and then underwent postoperative MRI (with and without
      contrast) within 1 week of surgery. RESULTS A total of 260 patients (55% of whom
      were males) met inclusion criteria for the study (age range 3 months to 84
      years). IOUS results showed a strong association with postoperative MRI results
      (phi = 0.693, p < 0.001) and an 81% intended GTR rate. In cases in which GTR was
      pursued, 19% had false-negative results. IOUS was able to accurately identify
      residual tumor in 100% of subtotal resection cases where resection was stopped
      due to invasion of tumor into eloquent locations. Cases involving gliomas had a
      75% intended GTR rate and a 25% false-negative rate. Cases involving metastatic
      tumors had an 87% intended GTR rate and a 13% false-negative rate. The
      sensitivity, specificity, negative predictive value, and positive predictive
      value are reported for IOUS in all included tumor pathologies, glioma cases, and
      metastatic tumor cases, respectively. CONCLUSIONS The use of IOUS may allow for a
      reliable imaging modality to achieve a more successful GTR of brain tumors in
      both adult and pediatric neurosurgical patients. When attempting GTR, the authors
      demonstrated an 81% GTR rate. The authors also report false-negative IOUS results
      in 19% of attempted GTR cases. The authors support the use of IOUS in both adult
      and pediatric CNS tumor surgery to improve surgical outcomes. However, further
      studies are warranted to address existing limitations with its use to further
      improve its efficacy and better define its role as an intraoperative imaging
      tool.

PMID- 29451455
TI  - Laser ablative therapy of sessile hypothalamic hamartomas in children using
      interventional MRI: report of 5 cases.
AB  - Hypothalamic hamartomas (HHs) are benign lesions that cause medically refractory
      seizures, behavioral disturbances, and endocrine dysfunction. Open resection of
      HHs does not guarantee seizure freedom and carries a relatively high risk of
      morbidity. Minimally invasive stereotactic laser ablation has recently been
      described as an effective and safe alternative for HH treatment. Prior studies
      have not, however, assessed HH lesion size and morphology, 2 factors that may
      influence treatment results and, ultimately, the generalizability of their
      findings. In this paper, the authors describe seizure outcomes for 5 pediatric
      patients who underwent laser ablation of sessile HHs. Lesions were treated using
      a frameless, interventional MRI-guided approach, which facilitated laser
      targeting to specific components of these complex lesions. The authors'
      experiences in these cases substantiate prior work demonstrating the
      effectiveness of laser therapy for HHs, while elucidating HH complexity as a
      potentially important factor in laser treatment planning, and in the
      interpretation of early studies describing this treatment method.

PMID- 29451457
TI  - Doreen Castle: 6 September 1924-3 January 2018.

PMID- 29451456
TI  - Clival meningocele causing bilateral hearing loss in a child due to superficial
      siderosis of the central nervous system: case report.
AB  - Superficial siderosis (SS) of the CNS is a rare and often unrecognized condition.
      Caused by hemosiderin deposition from chronic, repetitive hemorrhage in the
      subarachnoid space, it results in parenchymal damage in the subpial layers of the
      brain and spinal cord. T2-weighted MRI shows the characteristic hypointensity of
      hemosiderin deposition, classically occurring around the cerebellum, brainstem,
      and spinal cord. Patients present with progressive gait ataxia and sensorineural
      hearing impairment. Although there have been several studies, case reports, and
      review articles over the years, the clear pathophysiology of subarachnoid space
      hemorrhage remains to be elucidated. The proposed causes include prior intradural
      surgery, prior trauma, tumors, vascular abnormalities, nerve root avulsion, and
      dural abnormalities. Surgical repair of a dural defect associated with SS has
      been shown to be efficacious at preventing symptomatic progression. There have
      been several reports of dural defects within the spinal canal treated with
      surgery. Here, the authors present the first known case of a dural defect of the
      ventral skull base, namely a clival meningocele, presumed to be causing SS. In
      this case report, a 10-year-old girl with a history of head trauma at the age of
      3 years was found to have a clival meningocele 3 years after her original trauma.
      On follow-up imaging, the patient was found to have radiographic growth of the
      meningocele along with evidence of SS of the CNS. The patient was treated
      conservatively until she began to have progressive hearing loss. It was presumed
      that the growing meningocele was the source of her SS. An endoscopic endonasal
      transclival approach with a multilayer dural reconstruction was performed to fix
      the dural defect and repair the meningocele in hopes of mitigating the
      progression of her symptoms. At her 12-month postoperative follow-up, she was
      doing well, with audiometry showing a slightly decreased hearing threshold in the
      left ear but improved speech discrimination bilaterally. Postoperative MRI showed
      a stable level of hemosiderin deposition and meningocele repair. Long-term follow
      up will be necessary to evaluate for continued clinical stabilization or possible
      improvement.

PMID- 29451458
TI  - Immigrant mothers' preferences for children's sexes: A register-based study of
      fertility behaviour in Norway.
AB  - Parental sex preferences have been documented in many native populations, but
      much less evidence is available on immigrants' preferences for the sexes of their
      children. Using high-quality longitudinal register data from Norway, a country
      with a recent immigration history, we estimate hazards regression models of third
      birth risks by the sex composition of the first two children. A central question
      in the extant literature is whether the sex preferences of immigrant mothers
      match those observed in their country of origin, or if cultural adaption to local
      conditions is more important. Our analyses indicate that the sex preferences of
      immigrants generally match those previously documented for their native
      population, especially in the case of son preferences. The pattern of sex
      preferences is unmodified by the mother's exposure to the host society. In sum,
      our evidence generally supports theories emphasizing cultural persistence in
      preferences, rather than theories of adaption or immigrant selectivity.

PMID- 29451460
TI  - Early-Childhood Conduct Problems Predict Economic and Political Discontent in
      Adulthood: Evidence From Two Large, Longitudinal UK Cohorts.
AB  - Longstanding interest has been directed toward the etiology of sociopolitical
      attitudes. Personality traits have been posited as antecedents; however, most
      work addressing such links has been limited to cross-sectional study designs. The
      current study used data from two large (both Ns > 8,700), longitudinal cohorts of
      individuals from the United Kingdom who were parent-assessed on a measure of
      temperament (assessing anxiety, conduct problems, and hyperactivity) at age 5 or
      7 years and on a range of sociopolitical attitudes at age 30 or 33 years. In both
      cohorts, higher levels of childhood conduct problems predicted higher levels of
      economic and political discontent in adulthood. These associations were still
      evident when controlling for sex, childhood intelligence, and parental social
      class. In both cohorts, this pathway was partially mediated by educational
      attainment and achieved social class. These findings are consistent with the
      perspective that early-life temperament gives rise to adult political sentiment.

PMID- 29451459
TI  - Apiaceous Vegetables and Cruciferous Phytochemicals Reduced PhIP-DNA Adducts in
      Prostate but Not in Pancreas of Wistar Rats.
AB  - We previously showed rats fed with apiaceous vegetables, but not with their
      putative chemopreventive phytochemicals, reduced colonic DNA adducts formed by 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a dietary procarcinogen. We
      report here the effects of feeding apiaceous and cruciferous vegetables versus
      their purified predominant phytochemicals, either alone or combined, on prostate
      and pancreatic PhIP-DNA adduct formation. In experiment I, male Wistar rats
      received three supplemented diets: CRU (cruciferous vegetables), API (apiaceous
      vegetables), and CRU+API (both types of vegetables). In experiment II, rats
      received three diets supplemented with phytochemicals matched to their levels in
      the vegetables from experiment I: P + I (phenethyl isothiocyanate and indole-3
      carbinol), FC (furanocoumarins; 5-methoxypsoralen, 8-methoxypsoralen, and
      isopimpinellin), and COMBO (P + I and FC combined). After 6 days of feeding, PhIP
      was injected (10 mg/kg body weight) and animals were killed on day 7. PhIP-DNA
      adducts were analyzed by LC-MS/MS. In prostate, PhIP-DNA adducts were reduced by
      API (33%, P < .05), P + I (45%, P < .001), and COMBO (30%, P < .01). There were
      no effects observed in pancreas. Our results suggest that fresh vegetables and
      purified phytochemicals lower PhIP-DNA adducts and may influence cancer risk.

PMID- 29451461
TI  - With Trump Contraception Rules, Parties Trade Places in Courtroom.
AB  - The defendants and plaintiffs have changed sides in the latest courtroom drama
      surrounding the ACA requirement that health plans cover women's contraception.
      Where once the plaintiffs took exception on religious and moral grounds, it's now
      states and reproductive rights groups who support the requirements that are
      bringing the legal challenges.

PMID- 29451462
TI  - Prior Authorization: Do Insurers Pay Bonuses for Denying New-Drug Requests?
AB  - A MedPage Today blog post suggested that they do. A torrent of online comments
      followed. Most were somewhere on the spectrum of outraged. For their part,
      industry veterans said that they're unaware of bonuses for denials but agree that
      prior authorization processes should be more transparent.

PMID- 29451463
TI  - Sexual Harassment: Health Care, It Is #YouToo.
AB  - There's no question that sexual harassment-and worse-is common at the country's
      hospitals, clinics, research labs, and doctor's offices. Health care's gender
      imbalances create situations that are ripe for abuse: Women make up the majority
      of the workforce in health care but men still dominate positions of authority.

PMID- 29451464
TI  - Bundled Payment for Bundles of Joy.
AB  - Episode payments for maternity care, however, are particularly challenging for
      many reasons, including the fact that a full course of care starts with one
      patient and usually ends with at least two. Something needs to be done, because
      pregnancy, labor, and birth account for seven of the top 20 most expensive
      hospitalized conditions.

PMID- 29451465
TI  - The Pap Test: 20th Century Success Story, 21st Century Has-Been.
AB  - This old standby's ultimate demise will likely take place when cervical cancer
      incidence declines as the HPV vaccine starts to take effect at a population
      level. New guidelines are being written, but insurers could have a major
      influence on how closely those guidelines are followed. So far, though, they
      haven't waded very far into the Pap-HPV debate.

PMID- 29451466
TI  - What Women's Health Wants in Your Market.
AB  - Women are a key focus segment for health care organizations both because of the
      medical services they utilize as individuals and the influence they have on the
      health care of others. In one survey, 59% of women and 94% of working moms
      reported making or heavily influencing health care decisions for their entire
      families.

PMID- 29451467
TI  - Hemlibra's Remarkable Efficacy A Beacon For Hemophilia Patients.
AB  - Hemlibra demonstrates how far antibody science has progressed. Genentech's drug,
      approved late last year, connects two clotting factors to prevent the devastating
      bleeds in hemophilia patients with inhibitors. The high price may be offset by
      avoided costs in patients with factor VIII inhibitors.

PMID- 29451468
TI  - Health Care Resource Use and Costs Pre- and Post-Treatment Initiation With
      Linaclotide: Retrospective Analyses of a U.S. Insured Population.
AB  - As expected, pharmacy costs increased with the introduction of this new treatment
      in a market dominated by over-the-counter and generic treatments. On the other
      hand, outpatient GI-related and irritable bowel disease health care resource use
      and costs substantially decreased among commercial and Medicare patients
      following linaclotide treatment initiation.

PMID- 29451469
TI  - Evaluation of the warming sensation, acceptability, and local tolerability of an
      acetylcysteine oral solution containing the flavoring agent IFF flavor 316282 in
      the treatment of productive cough?.
AB  - OBJECTIVE: This open-label study sought to evaluate the warming sensation
      produced by IFF flavor 316282 in an acetylcysteine oral solution in subjects with
      productive cough. MATERIALS: 2% ace-tylcysteine oral solution (200 mg per 10 mL)
      containing IFF flavor 316282. METHODS: Subjects (N = 57; mean age 38.7 years; 58%
      female) with a productive cough lasting < 7 days and rated as mild to moderate in
      severity received 10 mL of study product. Warming sensation intensity was
      assessed using a 100-mm visual analog scale, its onset and duration using
      stopwatches, its acceptability using a 9-point scale (from "dislike extremely" to
      "like extremely") and the taste, texture, and overall acceptability of the
      solution using 5-point scales (from "unacceptable" to "excellent"). RESULTS: 53
      (93.0%) subjects perceived a warming sensation within 10 minutes of swallowing
      the solution; median onset was ~ 14 seconds, and median duration was ~ 2.8
      minutes. Warming sensation intensity increased from baseline by a mean of 29.2 mm
      when evaluated 60 seconds after ingestion. 30 subjects (52.6%) thought the
      warming sensation was "just about right"; 25 (43.9%) considered it "too weak" or
      "much too weak." Most subjects had positive overall ratings ("fair," "good," or
      "excellent") of the taste (79.0%), texture (96.5%), and solution (91.2%). No
      treatment-emergent adverse events were reported, and no evidence of oral mucosal
      irritation was found. CONCLUSION: The addition of IFF flavor 316282 to a 2%
      acetylcysteine oral solution produced a warming sensation with rapid onset and
      relatively short duration, which the majority of subjects found acceptable.?.

PMID- 29451470
TI  - Use of integrated clinical trial protocols - A survey in early medicines
      development?.
AB  - PURPOSE: To collect information on the use of integrated protocols in early
      clinical medicines development. MATERIALS AND METHODS: The questionnaire was
      mailed in fall 2014 to members of human pharmacology societies in Europe for
      anonymous responses via the online tool SurveyMonkey<sup>(r)</sup>. RESULTS: 97
      respondents reported on 164 integrated protocols overall. In general, integrated
      protocols comprised 2 or 3 trial elements. One third of integrated protocols
      involved patients. The most frequent trial elements were single dose, multiple
      dose, and food effect. Drug-drug interaction, age, gender, and relative/absolute
      bioavailability were less common elements. Ethnic bridging and mass balance were
      mentioned in single cases. Out of the entire spectrum of reported trial element
      combinations, single (ascending) dose plus multiple (ascending) dose was most
      frequent (90/164 protocols, 55%); 84% of integrated protocols used adaptive
      elements. 29%, 17%, and 8% of integrated protocols required 1, 2, or 3
      substantial amendments, respectively. Based on 118 protocols, competent authority
      approval was granted to 100, deficiency letters were issued 15 times and approval
      was refused in 3 cases. CONCLUSION: The use of integrated protocols is common
      practice in early medicines development. Most often single ascending dose and
      multiple ascending dose were the trial elements combined in one integrated
      protocol. Perceived main advantages were gain in time and reduced costs.
      Perceived main disadvantage was increased complexity.?.

PMID- 29451471
TI  - Calf muscle hypertrophy following S1 radiculopathy: A stress disorder caused by
      hyperactivity with variable response to treatmen.

PMID- 29451472
TI  - Hepcidin and proinflammatory markers in children with chronic kidney disease: A
      case-control study?.
AB  - BACKGROUND: Hepcidin is the main regulator of hepcidin-ferroportin axis and is
      elevated in children with chronic kidney disease (CKD). Anemia of CKD and its
      relation to hepcidin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF
      alpha), and high-sensitivity C-reactive protein (hs-CRP) in iron- and
      erythropoietin (EPO)-naive, non-dialyzed children with CKD is under-studied.
      MATERIALS AND METHODS: This case-control study aimed to study the levels of
      hepcidin and other proinflammatory markers (IL-6, TNF-alpha, hs-CRP) and their
      relation with anemia in iron- and erythropoietin-naive, non-dialysis CKD (stage 3
      - 5) patients. 32 pediatric CKD stage 3 - 5 patients aged 2 - 18 years without
      previous iron or EPO therapy were compared with 32 gender- and age-matched
      healthy controls. The CKD cases were also divided into three categories based on
      their serum ferritin levels and transferrin saturation (%TSAT): true iron
      deficiency, impaired iron trafficking, and no iron deficiency. The baseline iron
      status was then correlated with the serum hepcidin levels. RESULTS: Serum
      hepcidin, IL-6, and TNF-alpha levels were significantly elevated compared to
      controls. As CKD stage progressed, hemoglobin levels decreased, while serum
      hepcidin, IL6, TNF-alpha and hs-CRP levels increased significantly. Serum
      hepcidin levels correlated positively with IL-6 (r = 0.57, p = 0.001), TNF-alpha
      (r = 0.34, p = 0.05), hs-CRP (r = 0.36, p = 0.03), and ferritin (r = 0.07, p =
      0.001), while being inversely correlated with Total iron binding capacity (TIBC)
      (r = -0.50, p = 0.003), hemoglobin (r = -0.52, p = 0.001), and glomerular
      filtration rate (GFR) (r = -0.71, p = 0.000). Serum hepcidin levels were highest
      in those with impaired iron trafficking, followed by those with no iron
      deficiency, followed by those with absolute iron deficiency (55.16 vs. 49 vs.
      11.8, p = 0.005). Amongst those with no iron deficiency, hepcidin correlated
      negatively with hemoglobin (r = -0.752, p-value = 0.007). CONCLUSION: A positive
      correlation between hepcidin and other inflammatory biomarkers in non-dialyzed,
      iron- and EPO-naive pediatric CKD patients suggests a role of these markers in
      higher hepcidin production and its contribution to iron-restricted erythropoiesis
      across the spectrum of CKD. Median hepcidin levels were highest in those with
      impaired iron trafficking, followed by those with no iron deficiency, followed by
      those with absolute iron deficiency, suggesting that in an iron-replete state,
      high hepcidin levels inhibit iron absorption from the gut and release from iron
      storing cells, thus restricting erythropoiesis leading to anemia.?.

PMID- 29451473
TI  - Uremia: A historical reappraisal of what happened?.
AB  - Urea was identified as a urinary salt in 1662 and was the first organic bodily
      product to be synthesized <italic>in vitro</italic> in 1828. This heralded the
      end of an era that defined disease as an imbalance between vital life forces, and
      catalyzed the merging of organic chemical sciences into clinical medicine. The
      term <italic>uree</italic> (urea) was introduced in 1803, its accumulation in
      blood was dubbed <italic>uremie</italic> (uremia) in 1847, and the procedure for
      its removal from urine across semi-permeable membranes designated dialysis in
      1861. The advent of modern dialysis in the 20<sup>th</sup> century provided
      lifesaving replacement therapy for the universally fatal disease that progressive
      uremia had been theretofore. Today, the clearance of urea is no longer used as a
      marker to identify patients with kidney disease; rather it has been adopted as a
      measure of the adequacy of dialysis, and the "urea toxicity" of yesteryears has
      been replaced by that of dialyzable "uremic toxins". As a result, the use of the
      term uremia has become non-uniform and is now applied to variable scenarios
      ranging from "azotemia" to "kidney failure" and to the symptoms persisting in
      patients receiving maintenance hemodialysis. In the process, the quest for
      variably dialyzed uremic toxins has overshadowed the consideration that dialysis
      is an invasive non-physiologic process that operates counter to normal
      homeostasis and itself may be toxic.?.

PMID- 29451474
TI  - [A national debate to prepare the 2018 French bioethics law].

PMID- 29451475
TI  - [Trispecific broadly neutralizing antibodies for HIV immunoprophylaxis and
      immunotherapy?]

PMID- 29451476
TI  - [Sphingosine 1-phosphate as a new regulator of mitosis].

PMID- 29451477
TI  - [Regulation of hematopoietic stem and progenitor cells by stroma-derived
      extracellular vesicles].

PMID- 29451478
TI  - [HTLV-1 and dendritic cells: a relation-ship in search of maturation].

PMID- 29451479
TI  - [Sweet hijacking by the Tax oncoprotein of the Human T-cell lymphotropic virus
      type 1].

PMID- 29451480
TI  - [A new hope to fight invasive fungal infection].

PMID- 29451481
TI  - [Laser-assisted bioprinting: a novel approach for bone regeneration
      applications].

PMID- 29451482
TI  - [Nuclear sequestration of alarmins as a new adenoviral strategy to escape from
      innate immunity].

PMID- 29451483
TI  - [Role of ceramide metabolism in adipose browning: impact on energy homeostasis in
      obesity].

PMID- 29451484
TI  - [Biogenesis of small non-coding RNAs in animals].
AB  - In recent years, the discovery of small non-coding RNAs has opened an all new
      field in molecular biology. Indeed, these non-coding sequences give rise to
      powerful regulators of gene expression. Nowadays, different types of small non
      coding RNAs have been described. Of these, the best-characterized types are
      microRNAs, piRNAs (Piwi-interacting RNAs) and siRNAs (small interfering RNAs).
      Because of their fine-tuning important function in the regulation of gene and
      genome expression, an aberrant expression level of those small non-coding RNAs
      are associated to several pathologies. While this new research field is
      attracting attention, many aspects to be discovered. This review focuses on the
      biogenesis pathways of microRNAs, piRNAs and siRNAs in animals.

PMID- 29451485
TI  - [The roles of mast cells in radiation-induced damage are still an enigma].
AB  - Mast cells are immune cells that mature within the host tissue. The acquired
      phenotype is dictated by the tissue microenvironment, giving rise to diverse
      tissue-dependent phenotypes and functions. The lack of cellular models reflecting
      phenotypes found in vivo and important differences between human and rodent mast
      cells are obstacles to the understanding of their exact role in several
      pathophysiological processes. Studies published over the past few years showed
      that mast cells' role lies far beyond their involvement in allergy and
      anaphylaxis. Studies demonstrating their participation in innate immune responses
      as well as tissue scaring and vascular pathologies allowed the understanding of
      their role in several diseases, but also gave contradictory results, especially
      concerning tissue response to ionizing radiations. Nevertheless, therapeutic
      tools exist to target mast cells, such as degranulation inhibitors,
      antihistamine, protease inhibitors or tyrosine kinase receptors antagonists, and
      may offer some interesting new therapeutic perspectives to manage acute and
      chronic after-effects of radiation therapy.

PMID- 29451486
TI  - [Uveal melanoma, a model disease for splicing alterations and oncogenesis].
AB  - Uveal melanoma is a rare cancer in adults, whose highly stereotyped oncogenic
      events have been decrypted over the last decade. Its epidemiological, genetic and
      transcriptional features make it a remarkable model of oncogenesis. Malignant
      transformation involves almost mutually exclusive alteration of fundamental
      biologic pathways, including chromatin regulation with inactivation of BAP1,
      splicing with mutations of SF3B1 or translation with mutations of EIF1AX. Uveal
      melanoma analyses unraveled the splicing defect due to SF3B1 mutations.
      Understanding the link between these alterations and malignant transformation
      will be a key step to define novel therapeutic targets.

PMID- 29451487
TI  - [DNA sequencing by nanopores: achievements and prospects].
AB  - After years of development, the use of nanopore as a sensor to sequence DNA
      molecules is now a viable and promising possibility. Single base pair detection
      during DNA transport enables to record ultra-long threads with high
      parallelization and rates. I will present in this review the current
      methodologies based on electrical detection and biological nanopores and the new
      methods based on solid state nanopores and optical detection.

PMID- 29451488
TI  - [Can a diagnostic biomarker be prognostic?]

PMID- 29451489
TI  - [Hiroshima/Nagasaki survivors and their offspring: results of longterm
      epidemiological studies].
AB  - After the atomic bombing of Hiroshima and Nagasaki, long-term epidemiological
      studies were undertaken on the irradiated survivors and their offspring, and are
      still underway. These thorough studies involving tens of thousands of persons and
      published in hundreds of papers have shown a moderate increase in cancer
      incidence for irradiated survivors, with limited impact on their life span (loss
      of one year at most). In studies on the offspring of these survivors, no
      statistically significant deleterious effect on malformation frequency, incidence
      of mutations or mortality from cancer and other diseases has been seen so far.
      These data are actually the basis for current radiation safety levels; they show
      that health risks from radiation are limited, but they are not applicable to
      complex situations such as nuclear power station accidents that involve diverse
      types of radiation as well as contamination by radioactive materials.

PMID- 29451490
TI  - [Alternative bases and synthetic life].
AB  - Alternative bases that can fit into the DNA double helix have now been used in
      vivo to direct the synthesis of proteins incorporating unnatural amino acids.
      This bioengineering feat is significant at both the conceptual and the practical
      levels.

PMID- 29451491
TI  - The relationship between spatial configuration and functional connectivity of
      brain regions.
AB  - Brain connectivity is often considered in terms of the communication between
      functionally distinct brain regions. Many studies have investigated the extent to
      which patterns of coupling strength between multiple neural populations relates
      to behaviour. For example, studies have used 'functional connectivity
      fingerprints' to characterise individuals' brain activity. Here, we investigate
      the extent to which the exact spatial arrangement of cortical regions interacts
      with measures of brain connectivity. We find that the shape and exact location of
      brain regions interact strongly with the modelling of brain connectivity, and
      present evidence that the spatial arrangement of functional regions is strongly
      predictive of non-imaging measures of behaviour and lifestyle. We believe that,
      in many cases, cross-subject variations in the spatial configuration of
      functional brain regions are being interpreted as changes in functional
      connectivity. Therefore, a better understanding of these effects is important
      when interpreting the relationship between functional imaging data and cognitive
      traits.

PMID- 29451492
TI  - Extreme heterogeneity of influenza virus infection in single cells.
AB  - Viral infection can dramatically alter a cell's transcriptome. However, these
      changes have mostly been studied by bulk measurements on many cells. Here we use
      single-cell mRNA sequencing to examine the transcriptional consequences of
      influenza virus infection. We find extremely wide cell-to-cell variation in the
      productivity of viral transcription - viral transcripts comprise less than a
      percent of total mRNA in many infected cells, but a few cells derive over half
      their mRNA from virus. Some infected cells fail to express at least one viral
      gene, but this gene absence only partially explains variation in viral
      transcriptional load. Despite variation in viral load, the relative abundances of
      viral mRNAs are fairly consistent across infected cells. Activation of innate
      immune pathways is rare, but some cellular genes co-vary in abundance with the
      amount of viral mRNA. Overall, our results highlight the complexity of viral
      infection at the level of single cells.

PMID- 29451495
TI  - Perceptually Aware Image Retargeting for Mobile Devices.
AB  - Retargeting aims at adapting an original high-resolution photograph/video to a
      low-resolution screen with an arbitrary aspect ratio. Conventional approaches are
      generally based on desktop PCs, since the computation might be intolerable for
      mobile platforms (especially when retargeting videos). Typically, only low-level
      visual features are exploited, and human visual perception is not well encoded.
      In this paper, we propose a novel retargeting framework that rapidly shrinks a
      photograph/video by leveraging human gaze behavior. Specifically, we first derive
      a geometry-preserving graph ranking algorithm, which efficiently selects a few
      salient object patches to mimic the human gaze shifting path (GSP) when viewing a
      scene. Afterward, an aggregation-based CNN is developed to hierarchically learn
      the deep representation for each GSP. Based on this, a probabilistic model is
      developed to learn the priors of the training photographs that are marked as
      aesthetically pleasing by professional photographers. We utilize the learned
      priors to efficiently shrink the corresponding GSP of a retargeted
      photograph/video to maximize its similarity to those from the training
      photographs. Extensive experiments have demonstrated that: 1) our method requires
      less than 35 ms to retarget a photograph (or a video frame) on popular
      iOS/Android devices, which is orders of magnitude faster than the conventional
      retargeting algorithms; 2) the retargeted photographs/videos produced by our
      method significantly outperform those of its competitors based on a paired
      comparison-based user study; and 3) the learned GSPs are highly indicative of
      human visual attention according to the human eye tracking experiments.

PMID- 29451493
TI  - ERalpha promotes murine hematopoietic regeneration through the Ire1alpha-mediated
      unfolded protein response.
AB  - Activation of the unfolded protein response (UPR) sustains protein homeostasis
      (proteostasis) and plays a fundamental role in tissue maintenance and longevity
      of organisms. Long-range control of UPR activation has been demonstrated in
      invertebrates, but such mechanisms in mammals remain elusive. Here, we show that
      the female sex hormone estrogen regulates the UPR in hematopoietic stem cells
      (HSCs). Estrogen treatment increases the capacity of HSCs to regenerate the
      hematopoietic system upon transplantation and accelerates regeneration after
      irradiation. We found that estrogen signals through estrogen receptor alpha
      (ERalpha) expressed in hematopoietic cells to activate the protective Ire1alpha
      Xbp1 branch of the UPR. Further, ERalpha-mediated activation of the Ire1alpha
      Xbp1 pathway confers HSCs with resistance against proteotoxic stress and promotes
      regeneration. Our findings reveal a systemic mechanism through which HSC function
      is augmented for hematopoietic regeneration.

PMID- 29451494
TI  - Single-cell transcriptional dynamics of flavivirus infection.
AB  - Dengue and Zika viral infections affect millions of people annually and can be
      complicated by hemorrhage and shock or neurological manifestations, respectively.
      However, a thorough understanding of the host response to these viruses is
      lacking, partly because conventional approaches ignore heterogeneity in virus
      abundance across cells. We present viscRNA-Seq (virus-inclusive single cell RNA
      Seq), an approach to probe the host transcriptome together with intracellular
      viral RNA at the single cell level. We applied viscRNA-Seq to monitor dengue and
      Zika virus infection in cultured cells and discovered extreme heterogeneity in
      virus abundance. We exploited this variation to identify host factors that show
      complex dynamics and a high degree of specificity for either virus, including
      proteins involved in the endoplasmic reticulum translocon, signal peptide
      processing, and membrane trafficking. We validated the viscRNA-Seq hits and
      discovered novel proviral and antiviral factors. viscRNA-Seq is a powerful
      approach to assess the genome-wide virus-host dynamics at single cell level.

PMID- 29451496
TI  - Significantly enhanced visible light response in single TiO2 nanowire by nitrogen
      ion implantation.
AB  - The metal-oxide semiconductor TiO2 shows enormous potential in the field of
      photoelectric detection; however, UV-light absorption only restricts its
      widespread application. It is considered that nitrogen doping can improve the
      visible light absorption of TiO2, but the effect of traditional chemical doping
      is far from being used for visible light detection. Herein, we dramatically
      broadened the absorption spectrum of the TiO2 nanowire (NW) by nitrogen ion
      implantation and apply the N-doped single TiO2 NW to visible light detection for
      the first time. Moreover, this novel strategy effectively modifies the surface
      states and thus regulates the height of Schottky barriers at the
      metal/semiconductor interface, which is crucial to realizing high responsivity
      and a fast response rate. Under the illumination of a laser with a wavelength of
      457 nm, our fabricated photodetector exhibits favorable responsivity (8 A W-1)
      and a short response time (0.5 s). These results indicate that ion implantation
      is a promising method in exploring the visible light detection of TiO2.

PMID- 29451498
TI  - Current fluctuations across a nano-pore.
AB  - The frequency-dependent spectrum of current fluctuations through nano-scale
      channels is studied using analytical and computational techniques. Using a
      stochastic Nernst-Planck description and neglecting the interactions between the
      ions inside the channel, an expression is derived for the current fluctuations,
      assuming that the geometry of the channel can be incorporated through the lower
      limits for various wave-vector modes. Since the resulting expression turns out to
      be quite complex, a number of further approximations are discussed such that
      relatively simple expressions can be used for practical purposes. The analytical
      results are validated using Langevin dynamics simulations.

PMID- 29451497
TI  - Automated skeletal tissue quantification in the lower leg using peripheral
      quantitative computed tomography.
AB  - OBJECTIVE: In this paper we introduce a methodology for hard and soft tissue
      quantification at proximal, intermediate and distal tibia sites using peripheral
      quantitative computed tomography scans. Quantification of bone properties is
      crucial for estimating bone structure resistance to mechanical stress and
      adaptations to loading. Soft tissue variables can be computed to investigate
      muscle volume and density, muscle-bone relationship, and fat infiltration.
      APPROACH: We employed implicit active contour models and clustering techniques
      for automated segmentation and identification of bone, muscle and fat at
      [Formula: see text], [Formula: see text], and [Formula: see text] tibia length.
      Next, we calculated densitometric, area and shape characteristics for each tissue
      type. We implemented our approach as a multi-platform tool denoted by TIDAQ
      (tissue identification and quantification) to be used by clinical researchers.
      MAIN RESULTS: We validated the proposed method against reference quantification
      measurements and tissue delineations obtained by semi-automated workflows. The
      average Deming regression slope between the tested and reference method was 1.126
      for cross-sectional areas and 1.078 for mineral densities, indicating very good
      agreement. Our method produced high average coefficient of variation (R 2)
      estimates: 0.935 for cross-sectional areas and 0.888 for mineral densities over
      all tibia sites. In addition, our tissue segmentation approach achieved an
      average Dice coefficient of 0.91 over soft and hard tissues, indicating very good
      delineation accuracy. SIGNIFICANCE: Our methodology should allow for high
      throughput, accurate and reproducible automatic quantification of muscle and bone
      characteristics of the lower leg. This information is critical to evaluate risk
      of future adverse outcomes and assess the effect of medications, hormones, and
      behavioral interventions aimed at improving bone and muscle strength.

PMID- 29451499
TI  - Characterising the frequency response of impedance changes during evoked
      physiological activity in the rat brain.
AB  - OBJECTIVE: Electrical impedance tomography (EIT) can image impedance changes
      associated with evoked physiological activity in the cerebral cortex using an
      array of epicortical electrodes. An impedance change is observed as the
      externally applied current, normally confined to the extracellular space is
      admitted into the conducting intracellular space during neuronal depolarisation.
      The response is largest at DC and decreases at higher frequencies due to
      capacitative transfer of current across the membrane. Biophysical modelling has
      shown that this effect becomes significant above 100 Hz. Recordings at DC,
      however, are contaminated by physiological endogenous evoked potentials. By
      moving to 1.7 kHz, images of somatosensory evoked responses have been produced
      down to 2 mm with a resolution of 2 ms and 200 MUm. Hardware limitations have so
      far restricted impedance measurements to frequencies  <2 kHz. The purpose of this
      work was to establish the optimal frequency for extending EIT to image throughout
      the brain and to characterise the response at frequencies  >2 kHz using improved
      hardware. APPROACH: Impedance changes were recorded during forepaw somatosensory
      stimulation in both cerebral cortex and the VPL nucleus of the thalamus in
      anaesthetised rats using applied currents of 1 kHz to 10 kHz. MAIN RESULTS: In
      the cortex, impedance changed by -0.04 +/- 0.02 % at 1 kHz, reached a peak of 
      0.13 +/- 0.05 % at 1475 Hz and decreased to -0.05 +/- 0.02 % at 10 kHz. At these
      frequencies, changes in the thalamus were -0.26 +/- 0.1%, -0.4 +/- 0.15 % and 
      0.08 +/- 0.03 % respectively. The signal-to-noise ratio was also highest at 1475
      Hz with values of -29.5 +/- 8 and -31.6 +/-10 recorded from the cortex and
      thalamus respectively. Signficance: This indicates that the optimal frequency for
      imaging cortical and thalamic evoked activity using fast neural EIT is 1475 Hz.

PMID- 29451500
TI  - Tunable electronic, electrical and optical properties of graphene oxide sheets by
      ion irradiation.
AB  - The tunable electronic, electrical and optical properties of graphene oxide (GO)
      sheets were investigated using a controlled reduction by 500 keV Ar+-ion
      irradiation. The carbon to oxygen ratio of the GO sheets upon the ion beam
      reduction has been estimated using resonant Rutherford backscattering
      spectrometry analyses and its effect on the electrical and optical properties of
      GO sheets has been studied using sheet resistance measurements and
      photoluminescence (PL) measurements. The restoration of sp 2-hybridized carbon
      atoms within the sp 3 matrix is found to be increases with increasing the Ar+-ion
      fluences as evident from Fourier transform infrared, and x-ray absorption near
      edge structure measurements. The decrease in the number of disorder-induced local
      density of states (LDOSs) within the pi-pi* gap upon the reduction causes the
      shifting of PL emission from near infra-red to blue region and decreases the
      sheet resistance. The improved electrical and optical properties of GO sheets
      were correlated to the decrease in the number of LDOSs within the pi-pi* gap. Our
      experimental investigations suggest ion beam irradiation is one of an effective
      approaches to reduce GO to RGO and to tailor its electronic, electrical and
      optical properties.

PMID- 29451501
TI  - Transitions in physiological coupling between heartbeat and pulse across sleep
      stages.
AB  - OBJECTIVE: The aim of this study is to investigate the coupling behavior between
      heartbeat and pulse of blood flow at different sleep stages, and to explore the
      feasibility of using this coupling strength for automatic sleep staging.
      APPROACH: The electrocardiogram and photoplethysmography signals are recorded
      during sleep, and R-wave-to-R-wave intervals (RRI) and pulse-to-pulse intervals
      (PPI) are extracted respectively. The detrended cross-correlation analysis (DCCA)
      is applied to quantify long-range cross correlations between the RRIs and PPIs
      across sleep stages. The DCCA scaling exponents are used as the indicator of
      coupling strength between heartbeat and pulse, and are compared with detrended
      fluctuation analysis (DFA) scaling exponents of RRIs and PPIs in the application
      of sleep stage discrimination. MAIN RESULTS: We find the DCCA scaling exponents
      between RRIs and PPIs decrease monotonously from wake, REM sleep to light and
      deep sleep, indicating that the coupling strength between heartbeat and pulse are
      reduced gradually when entering deep sleep. Statistical analysis shows that the
      DCCA scaling exponents possess better discrimination ability between wake/REM
      sleep and light/deep sleep, compared with DFA scaling exponents of RRIs and PPIs.
      SIGNIFICANCE: Our study reveals the coupling strength between heartbeat and pulse
      changes regularly across sleep stages, which may help understand the regulation
      mechanism underlying the cardiovascular system. The DCCA scaling exponents
      between RRIs and PPIs can be used as an indicator for measuring vigilance level
      and automatic sleep staging.

PMID- 29451503
TI  - ?

PMID- 29451502
TI  - ?

PMID- 29451504
TI  - [The COMPASS study].

PMID- 29451505
TI  - [Is ejection fraction sufficient to establish indication for cardioverter
      defibrillator implantation in heart failure?]

PMID- 29451506
TI  - [Ten questions on the management of patients with acute pulmonary embolism].
AB  - Clinical management of acute pulmonary embolism has changed over the years based
      on new evidence on diagnosis, prognostic stratification and treatment. The
      increasing availability of computed tomography angiography has made the diagnosis
      faster and accurate, although with some concern on radiation exposure and
      potential for overdiagnosis. The efficacy and safety of simple-to-use oral
      anticoagulant agents acting as selective direct inhibitors of coagulation
      certainly offer considerable benefits to the patients. However, the appropriate
      use of these agents is necessary to maintain an optimal risk-benefit ratio. This
      paper reports answers to ten frequently asked questions in the management of
      patients with suspected or proven acute pulmonary embolism.

PMID- 29451507
TI  - [Appropriateness in Cardiology: a statement of the ANMCO Veneto Region].
AB  - Inappropriate tests are responsible for longer waiting lists, higher economical
      costs for the National Health System and major clinical risks due to radiation
      exposure from prescription abuse of diagnostic testing. Clinical
      inappropriateness frequently derives from poor knowledge of guidelines,
      "defensive medicine" approach and/or repeat requests of patients and family
      members. About one third of non-invasive imaging tests are considered
      inappropriate.In order to define the most appropriate instruments for the follow
      up of the most common cardiovascular diseases with the highest risk of
      inappropriateness, all the cardiologists of the Veneto Region (Italy), along with
      the local chapters of the main national cardiology societies and general
      practitioners have been involved by the Regional Section of the Italian
      Association of Hospital Cardiologists (ANMCO) in several scientific meetings on
      the following topics: hypertension, chronic ischemic heart disease, valvular
      heart disease, heart failure, and atrial fibrillation. This has led to the
      present document where: (i) the most appropriate clinical and diagnostic
      strategies are taken into account, and (ii) the most robust scientific evidence
      is provided for the regulatory commission of the Veneto Region Health Service to
      identify inappropriateness, prescription unsuitability, and economical
      sustainability.

PMID- 29451508
TI  - [Heart failure with mid-range ejection fraction. Looking for Middle Earth?]
AB  - The latest guidelines of the European Society of Cardiology have proposed a
      classification of heart failure based on left ventricular ejection fraction.
      Three distinct groups have been identified: heart failure with ejection fraction
      >=50%, between 40 and 49%, and <40%. This classification has the advantage to be
      simple but it has been criticized because it is not clear whether the mid-range
      ejection fraction group is an independent category or just a transition phase
      between the other two groups. The purpose of this article is to discuss the
      characteristics and prognosis of mid-range ejection fraction heart failure on the
      basis of current evidence.

PMID- 29451509
TI  - [Diagnosis and treatment of blood volume changes in acute heart failure - a brief
      practical guide].
AB  - The correct management of acute heart failure continues to pose diagnostic and
      therapeutic challenges. In particular, administering the right type and dose of
      fluids and drugs, thus avoiding fluid overload while establishing organ
      perfusion, is of key importance in stabilizing critical patients and improving
      prognosis. A correct estimate of the fluid volume status, however, may be
      difficult, as the invasive evaluation of cardiac filling pressures by cardiac
      catheterization is limited in routine medical practice, and there is no universal
      consensus on the best tools for its non-invasive evaluation. Here we review
      current evidence about diagnosis and treatment of fluid volume abnormalities in
      acute heart failure according to the most recent guidelines.

PMID- 29451510
TI  - [Under-reporting of adverse drug reactions, a problem that also involves
      medicines subject to additional monitoring. Preliminary data from a single-center
      experience on novel oral anticoagulants].
AB  - BACKGROUND: Spontaneous reporting system is the most widely used method by
      pharmacovigilance centers. Its "voluntary nature" represents the main cause of
      adverse drug reaction (ADR) under-reporting phenomena. The aim of this study was
      to point out the issue of ADR under-reporting from doctors, particularly serious
      ADRs and adverse reactions caused by medicinal products subject to additional
      monitoring, such as novel oral anticoagulants (NOACs). METHODS: Only serious ADRs
      were analyzed, defined as death, life-threatening ADR, hospitalization (initial
      or prolonged), disability (significant or permanent), congenital anomaly.
      Firstly, we analyzed suspected adverse reaction alerts to NOACs submitted to the
      Area Vasta 2 (ASUR Marche) pharmacovigilance center, from June 16, 2013 to
      January 14, 2017. Then, we examined alerts coming from all over Italy and from
      the Marche Region in the same time period. Secondly, the analysis was focused on
      the Senigallia hospital (where we had an easy access to the medical records
      archive); patients who experienced an ADR in that time period were identified
      retrospectively and an alert was submitted. Thirdly, from January 15, 2017 to
      March 15, 2017, suspected ADR alerts were submitted prospectively. RESULTS: Phase
      1: in 43 months, 1625 alerts were submitted from all over Italy, 18 from the
      Marche Region (one of them from the Senigallia hospital). Phase 2: 8 suspected
      serious ADRs were collected retrospectively (2 fatal and 3 life-threatening).
      Phase 3: in only 2 months, 7 serious ADRs were observed prospectively (2 fatal
      and 1 life-threatening). CONCLUSIONS: Our study shows that among doctors the
      under-reporting phenomenon is remarkable and it also involves medicinal products
      subject to additional monitoring and serious ADRs, including deaths.

PMID- 29451511
TI  - [Endovascular treatment of symptomatic carotid artery dissection].
AB  - Internal carotid artery dissection is one of the possible causes of stroke in
      young adults. The effectiveness of medical therapy alone is often limited and
      endovascular strategy should be considered, particularly in the presence of
      persisting neurological symptoms. Currently, there is no general consensus on the
      most appropriate therapeutic strategy to follow in symptomatic carotid artery
      dissection. We here report a case of symptomatic carotid artery dissection
      treated with an endovascular approach, and we review the recent literature
      regarding this therapeutic strategy. Materials and methods for performing
      endovascular treatment are also described, along with the possible steps to
      follow. Data in the literature and our clinical experience suggest that stenting
      is promising in patients with internal carotid artery dissection and should be
      considered as a valid therapeutic strategy in case of failure of medical therapy
      in highly experienced centers.

PMID- 29451512
TI  - [Antegrade and retrograde approach through the venous graft for treating a
      chronic total occlusion in a patient with acute coronary syndrome complicated by
      pulmonary edema].
AB  - Percutaneous treatment of chronic total occlusions (CTO) is one of the major
      challenges in contemporary interventional cardiology. These lesions are
      identified in 15% to 30% of all patients referred for coronary angiography.
      Percutaneous coronary intervention (PCI) of CTOs is technically challenging and
      requires familiarity with advanced interventional techniques as well as specialty
      equipment. The choice of strategy and materials is based on clinical features and
      coronary anatomy; the correct choice is essential to improve the success
      probability. PCI of CTOs is usually performed in stable coronary artery disease.
      We here report a case of a PCI of an anterior descending CTO grafted by a
      saphenous vein in an 83-year-old man admitted for acute coronary syndrome
      complicated by hypotensive pulmonary edema.

PMID- 29451515
TI  - [Promoting evidence-based gastroenterology: back to the future.]
AB  - Evidence-based medicine continues to thrive thanks to the publication of a
      considerable amount of papers focusing on data collection and sharing. Assessment
      of the accuracy of diagnostic tests still remains highly deficient, often leading
      to inappropriate clinical decision-making. Like most other doctors,
      gastroenterologists as well have to face the ever-growing availability of complex
      and expensive exams, being charged with the task of choosing the best diagnostic
      option and interpreting test results. It is therefore advisable to provide
      specialists with the tools they need to evaluate the available literature data.
      Among these, it deserves mentioning the residential courses organized by the
      Evidence-based Gastroenterology & Hepatology Club, which have been attended by
      hundreds of participants over the last years.

PMID- 29451516
TI  - [Evidence-based medicine vs personalized medicine.]
AB  - Evidence-based medicine (EBM) and personalized medicine (PM) are driven by two
      diverse modes of reasoning about "evidence making". EBM has been criticized since
      his quality mark has been misappropriated by vested interests, the benefits
      statistically significant may be marginal in clinical practice, rigid rules and
      technology may produce care that is management driven rather than patient
      centered. On the contrary PM (or "precision medicine") refers to the tailoring of
      medical treatment to the specific characteristics of each patient involving the
      ability to classify individuals into subpopulations that are uniquely susceptible
      to a specific treatment, sparing expense and side effects and is derived from
      doubts on the results of subgroup analyses and on non responders in clinical
      trials typical of EBM. While both paradigms are epistemically sound they cannot,
      and should not, be hybridized into a unique model. Rather they ought to represent
      two compatible, but alternative ways of informing the Clinical practice. The
      clinicians may expect to see their responsibility increasing as they will deal
      with diverse, but equally compelling ways of reasoning and deciding about which
      intervention will qualify as the "best one" in each individual case.

PMID- 29451517
TI  - [Burden of diverticular disease: an observational analysis based on Italian real
      world data.]
AB  - INTRODUCTION: Diverticular disease (DD) represent a wide variety of conditions
      associated with the presence of diverticula in the colon. The most serious form
      is an acute episode of diverticulitis which can lead to hospitalization and
      surgery with various types of consequences. The main aim of this study was to
      evaluate, from both cross-sectional and longitudinal perspective, the economic
      burden of diverticulitis in the real practice. METHOD: A deterministic linkage
      was performed at individual user level between the different administrative
      sources of the Marche Region through anonymised ID number for a period of
      analysis between 1 January 2008 and 31 December 2014. We enrolled all patients
      with at least one hospitalization for "diverticulitis of the colon without
      mention of haemorrhage" (ICD-9-CM code 562.11) or "diverticulitis of the colon
      with haemorrhage" (ICD-9-CM code 562.13) as primary or secondary diagnosis. Cost
      and outcome were analysed considering transversally (for contemporaneous) and
      longitudinal (for cohort) perspective. Hospital mortality at one year after
      discharge was evaluated by mortality rates and Kaplan-Meier curve considering the
      surgery performed (or not performed) during the index hospitalization. RESULTS:
      Considering the cross-sectional perspective, 427 patients per year were estimated
      (about 35 patients per 100,000 adult residents) with an average number of
      hospitalization equal to 1.14. The direct healthcare costs incurred by the Marche
      region for episodes of diverticulitis in 2008-2014 amounted to approximately ?
      11.4 million (? 1.6 million a year), of which ? 10.9 million (95.5%) for the
      hospitalizations, ? 246,000 (2.1%) for pharmaceutical treatment and ? 270,000
      (2.4%) for specialist outpatient services. The cohort analysis estimates an intra
      hospital mortality rate equal to 5.9 per 100 patients' year (5.5 for non-surgery
      patients and 8.9 for surgery patients - P<0.05). Kaplan-Meier curve demonstrate
      that there were no differences between intra-hospital mortality due to surgery
      during index hospitalization. CONCLUSIONS: Our study is the first analysis in
      Italy to use real-world data to measure the burden of DD with a cross-sectional
      and longitudinal perspective. This study could be useful for decision maker that
      could quantify the economic and epidemiological burden of DD in hospital.

PMID- 29451518
TI  - [Access to hepatitis C treatment: a lesson for the future.]
AB  - The new generation of direct acting antivirals (DAA) for the treatment of chronic
      hepatitis C virus infection has revolutionized the previous scenario and has put
      the institutions under test because of the high cost of therapies. An analysis of
      what has happened over the last three years, especially in Italy, helps us
      understand how price negotiation has been managed, and what criteria were chosen
      at first to allow limited access on the basis of the need of patient care. This
      allows to focus on some important issues and to identify the challenges ahead in
      the near future.

PMID- 29451519
TI  - [Hepatitis C virus infections: is it only e liver disease?]
AB  - Hepatitis C virus (HCV) infection is widely diffused in general population, and
      the likelihood that an infected individual is affected by other disesases is
      high. A lot of epidemiological and explicative studies, even if with different
      levels of evidence, reported a potential effect of HCV infection -by direct and
      indirect mechanisms- on the pathogenesis of extrahepatic comorbidities related to
      dysregulation of the immune system, or cardiometabolic comorbidities like
      diabetes, neuropsychiatric disorders, chronic kidney disease, cardiovascular
      alterations, etc. Along this line, some studies observed a positive effect of
      viral eradication on extrahepatic diseases. However, these data are some time
      affected by selection bias and by the fact that they are mostly focuded on
      populations underwent interferon-based therapies. Until now only few data are
      available on the impact of viral eradication by direct antiviral agents on
      extrahepatic manifestations of HCV. Consistently, to draw conclusions, further
      validation studies are needed also stratifying the effect of viral eradication
      according to lenght and severity of both hepatic and extrahepatic damage.

PMID- 29451520
TI  - [Hepatitis C virus infection. From clinical guidelines to clinical practice and
      personalization of cure.]
AB  - Although clinical guidelines provide clear indications on the treatment of
      patients with chronic HCV related liver disease, there are still clinical
      situations in which clinicians experience and judgment remain essential in the
      proper patient management. These are mainly represented by antiviral therapy in
      patients with decompensated liver disease, especially if they are candidates for
      liver transplantation or with significant comorbidities and complex
      pharmacological therapies. Antiviral retreatment of patients who failed a regimen
      containing an NS5A protease inhibitor still appears to be a delicate context in
      which no solid recommendations are provided, especially in patients with HCV
      genotype 3 and decompensated cirrhosis. The follow-up of patients without
      cirrhosis who have obtained viral eradication is still controversial, in the
      absence of prospective clinical trials. With the advent of new drugs and shorter
      treatments in patients with mild liver disease, the subject of discussion and
      recommendations could become the evaluation of early HCV viral kinetics after the
      onset of treatment to decide in every patient when to stop antivirals.

PMID- 29451521
TI  - [Personalized healthcare in hepatocellular carcinoma. Multi-society Italian
      position paper.]
AB  - Hepatocellular carcinoma (HCC) is a neoplasm characterized by both clinical and
      biological heterogeneity. Its management requires the expertise of multiple
      medical specialists and is made complex by the old age of most patients,
      frequently showing comorbidities. Therefore, HCC management needs a
      multidisciplinary approach. The aim of this article is to illustrate multi
      society recommendations regarding the management of HCC patients, from diagnosis
      to treatment and follow-up. In particular, in every stage, HCC treatment
      comprises multiple alternatives and the best option for every patient should be
      decided by a multidisciplinary team.

PMID- 29451522
TI  - [Management of benign esophageal strictures: a literature review.]
AB  - The management of benign esophageal strictures is challenging. The first strategy
      includes endoscopic dilation using bougies or balloons. Although the immediate
      success rate of these is up to 90%, about 30-40% of patients experience recurrent
      dysphagia within the first year of follow-up. The management of refractory
      stenosis involves repeated sessions of endoscopic dilation. In order to obtain
      long-lasting functional results, alternative treatments have been developed, such
      as the use of self-expanding stents, particularly indicated in subgroups of
      patients with post-surgical stenosis or post-radiation therapy. If this approach
      fails, other possibilities are represented by self-decoding, PEG/J-tube
      positioning and, finally, reconstructive surgery.

PMID- 29451523
TI  - [Towards new therapeutic paradigms beyond symptom control in the management of
      inflammatory bowel diseases.]
AB  - Inflammatory bowel diseases, Crohn's disease and ulcerative colitis are chronic
      relapsing conditions that may result in progressive bowel damage, high risk of
      complications, surgery and permanent disability. The conventional therapeutic
      approach for inflammatory bowel diseases is based mainly on symptom control.
      Unfortunately, a symptom-based therapeutic approach has little impact on major
      long-term disease outcomes. In other chronic disabling conditions such as
      diabetes, hypertension and rheumatoid arthritis, the development of new
      therapeutic approaches has led to better outcomes. In this context a "treat to
      target" strategy has been developed. This strategy is based on identification of
      high-risk patients, regular assessment of disease activity by means of objective
      measures, adjustment of treatment to reach the pre-defined target. A treat to
      target approach has recently been proposed for inflammatory bowel disease with
      the aim at modifying the natural history of the disease. In this review, the
      evidence and the limitations of the treat to target paradigm in inflammatory
      bowel disease are analyzed and discussed.

PMID- 29451524
TI  - [Diet and gut microbiota: two sides of the same coin?]
AB  - Gut microbiota is a complex ecosystem, resident in the digestive tract, exerting
      multiple functions that can have a significant impact on the pathophysiology of
      the host organism. The composition and functions of this "superorganism" are
      influenced by many factors, and among them, the host's dietary habits seem to
      have a significant effect. Dietary changes in the evolution of human history and
      in the different stages of life of the human subjects are responsible for
      qualitative and functional modification of gut microbiota. At the same time, the
      different dietary models adopted in worldwide geographic areas take into account
      the inter-individual differences concerning composition and microbial function.
      This close relationship between diet, gut microbiota and host seems, in fact, to
      be responsible for the protection or predisposition to develop several metabolic,
      immunological, neoplastic and functional diseases. Thus, several studies have
      evaluated the impact of diet and lifestyle modification strategies on gut
      microbiota composition and functions which, in turn, seems to affect the
      effectiveness of such therapeutic measures. Gut microbiota manipulation
      strategies, as complementary to dietary modifications, represent a fascinating
      field of research, even if consolidated data are still lacking.

PMID- 29451526
TI  - ?

PMID- 29451525
TI  - [Chronic pancreatitis: new definition and perspectives.]
AB  - Chronic pancreatitis has been considered over the past years as a single disease,
      alcohol-induced and different from acute pancreatitis, in terms of etiology and
      prognosis. Actually, the introduction of a new concept of chronic pancreatitis,
      now considered as a fibroinflammatory process caused by multiple factors (toxic
      metabolic, genetic, immunologic, obstructive), allow to better understand the
      pathogenesis of this complex disease. Furthermore, the discover of peculiar forms
      of chronic pancreatitis (autoimmune, paraduodenal, associated to gene mutations),
      different in term of clinical aspects, findings at imaging, prognosis and
      therapy, radically changed the concept of the disease. In this brief review, we
      described the impact of this new concept in the comprehension of pathogenesis, in
      the definition of peculiar forms of chronic pancreatitis, and in the clinical and
      therapeutic approach of chronic pancreatitis.

PMID- 29451527
TI  - CORRIGENDUM FOR "Effect of Growth Hormone on Uterine Receptivity in Women With
      Repeated Implantation Failure in an Oocyte Donation Program: A Randomized
      Controlled Trial".
AB  - [This corrects the article DOI: 10.1210/js.2017-00359.].

PMID- 29451528
TI  - Reviewer training to assess knowledge translation in funding applications is long
      overdue.
AB  - Background: Health research funding agencies are placing a growing focus on
      knowledge translation (KT) plans, also known as dissemination and implementation
      (D&I) plans, in grant applications to decrease the gap between what we know from
      research and what we do in practice, policy, and further research. Historically,
      review panels have focused on the scientific excellence of applications to
      determine which should be funded; however, relevance to societal health
      priorities, the facilitation of evidence-informed practice and policy, or
      realizing commercialization opportunities all require a different lens.
      Discussion: While experts in their respective fields, grant reviewers may lack
      the competencies to rigorously assess the KT components of applications. Funders
      of health research-including health charities, non-profit agencies, governments,
      and foundations-have an obligation to ensure that these components of funding
      applications are as rigorously evaluated as the scientific components. In this
      paper, we discuss the need for a more rigorous evaluation of knowledge
      translation potential by review panels and propose how this may be addressed.
      Conclusion: We propose that reviewer training supported in various ways including
      guidelines and KT expertise on review panels and modalities such as online and
      face-to-face training will result in the rigorous assessment of all components of
      funding applications, thus increasing the relevance and use of funded research
      evidence. An unintended but highly welcome consequence of such training could be
      higher quality D&I or KT plans in subsequent funding applications from trained
      reviewers.

PMID- 29451529
TI  - Improving the peer review of narrative literature reviews.
AB  - As the size of the published scientific literature has increased exponentially
      over the past 30 years, review articles play an increasingly important role in
      helping researchers to make sense of original research results. Literature
      reviews can be broadly classified as either "systematic" or "narrative".
      Narrative reviews may be broader in scope than systematic reviews, but have been
      criticised for lacking synthesis and rigour. The submission of more scientific
      manuscripts requires more researchers acting as peer reviewers, which requires
      adding greater numbers of new reviewers to the reviewing population over time.
      However, whereas there are many easily accessible guides for reviewers of primary
      research manuscripts, there are few similar resources to assist reviewers of
      narrative reviews. Here, I summarise why literature reviews are valued by their
      diverse readership and how peer reviewers with different levels of content
      expertise can improve the reliability and accessibility of narrative review
      articles. I then provide a number of recommendations for peer reviewers of
      narrative literature reviews, to improve the integrity of the scientific
      literature, while also ensuring that narrative review articles meet the needs of
      both expert and non-expert readers.

PMID- 29451530
TI  - Publication proportions for registered breast cancer trials: before and following
      the introduction of the ClinicalTrials.gov results database.
AB  - Background: To limit selective and incomplete publication of the results of
      clinical trials, registries including ClinicalTrials.gov were introduced. The
      ClinicalTrials.gov registry added a results database in 2008 to enable
      researchers to post the results of their trials as stipulated by the Food and
      Drug Administration Amendment Act of 2007. This study aimed to determine the
      direction and magnitude of any change in publication proportions of registered
      breast cancer trials that occurred since the inception of the ClinicalTrials.gov
      results database. Methods: A cross-sectional study design was employed using
      ClinicalTrials.gov, a publicly available registry/results database as the primary
      data source. Registry contents under the subcategories 'Breast Neoplasms' and
      'Breast Neoplasms, Male' were downloaded on 1 August 2015. A literature search
      for included trials was afterwards conducted using MEDLINE and DISCOVER databases
      to determine publication status of the registered breast cancer trials. Results:
      Nearly half (168/340) of the listed trials had been published, with a median time
      to publication of 24 months (Q1 = 14 months, Q3 = 42 months). Only 86 trials were
      published within 24 months of completion. There was no significant increase in
      publication proportions of trials that were completed before the introduction of
      the results database compared to those completed after (OR = 1.00, 95 % CI = .61
      to 1.63; adjusted OR = 0.84, 95 % CI = .51 to 1.39). Characteristics associated
      with publication included trial type (observational versus interventional
      adjusted OR = .28, 95 % CI = .10 to .74) and completion/termination status
      (terminated versus completed adjusted OR = .22, 95 % CI = .09 to .51).
      Conclusions: Less than a half of breast cancer trials registered in
      ClinicalTrials.gov are published in peer-reviewed journals.

PMID- 29451531
TI  - Critical evaluation of the guidelines of the Finnish Advisory Board on Research
      Integrity and of their application.
AB  - We have national guidelines for the responsible conduct of research (RCR) and
      procedures for handling allegations of misconduct in Finland. The guidelines have
      been formulated and updated by the Finnish Advisory Board on Research Integrity
      (TENK). In this article, we introduce and evaluate the national RCR guidelines.
      We also present statistics of alleged and proven RCR violation cases and
      frequency of appeals to TENK on the decisions or procedures of the primary
      institutions. In addition, we analyze the available data on seven investigated
      cases in more detail. Positive aspects in the Finnish system are a fairly good
      infrastructure to investigate suspected RCR violations and a wide concept of RCR
      violations, which consists of fabrication, falsification, plagiarism,
      misappropriation, and other misbehaviors. However, the guidelines contain poorly
      elaborated definitions, do not treat the complainant and the suspect in an equal
      way, and need to be revised. Confusion about the concepts and criteria of the RCR
      violations seems to be common in primary institutions and among the complainants.
      Even if research institutions and universities have officially adhered to the
      national RCR guidelines, slipping from the guidelines occurs quite commonly. All
      these factors lead to frequent dissatisfaction with the decisions or procedures
      applied, high rate of appeals to TENK, and far from optimal functionality of the
      system.

PMID- 29451532
TI  - Using democracy to award research funding: an observational study.
AB  - Background: Winning funding for health and medical research usually involves a
      lengthy application process. With success rates under 20%, much of the time spent
      by 80% of applicants could have been better used on actual research. An
      alternative funding system that could save time is using democracy to award the
      most deserving researchers based on votes from the research community. We aimed
      to pilot how such a system could work and examine some potential biases. Methods:
      We used an online survey with a convenience sample of Australian researchers.
      Researchers were asked to name the 10 scientists currently working in Australia
      that they thought most deserved funding for future research. For comparison, we
      used recent winners from large national fellowship schemes that used traditional
      peer review. Results: Voting took a median of 5 min (inter-quartile range 3 to 10
      min). Extrapolating to a national voting scheme, we estimate 599 working days of
      voting time (95% CI 490 to 728), compared with 827 working days for the current
      peer review system for fellowships. The gender ratio in the votes was a more
      equal 45:55 (female to male) compared with 34:66 in recent fellowship winners,
      although this could be explained by Simpson's paradox. Voters were biased towards
      their own institution, with an additional 1.6 votes per ballot (inter-quartile
      range 0.8 to 2.2) above the expected number. Respondents raised many concerns
      about the idea of using democracy to fund research, including vote rigging,
      lobbying and it becoming a popularity contest. Conclusions: This is a preliminary
      study of using voting that does not investigate many of the concerns about how a
      voting system would work. We were able to show that voting would take less time
      than traditional peer review and would spread the workload over many more
      reviewers. Further studies of alternative funding systems are needed as well as a
      wide discussion with the research community about potential changes.

PMID- 29451533
TI  - Recruitment of reviewers is becoming harder at some journals: a test of the
      influence of reviewer fatigue at six journals in ecology and evolution.
AB  - Background: It is commonly reported by editors that it has become harder to
      recruit reviewers for peer review and that this is because individuals are being
      asked to review too often and are experiencing reviewer fatigue. However,
      evidence supporting these arguments is largely anecdotal. Main body: We examine
      responses of individuals to review invitations for six journals in ecology and
      evolution. The proportion of invitations that lead to a submitted review has been
      decreasing steadily over 13 years (2003-2015) for four of the six journals
      examined, with a cumulative effect that has been quite substantial (average
      decline from 56% of review invitations generating a review in 2003 to just 37% in
      2015). The likelihood that an invitee agrees to review declines significantly
      with the number of invitations they receive in a year. However, the average
      number of invitations being sent to prospective reviewers and the proportion of
      individuals being invited more than once per year has not changed much over these
      13 years, despite substantial increases in the total number of review invitations
      being sent by these journals-the reviewer base has expanded concomitant with this
      growth in review requests. Conclusions: The proportion of review invitations that
      lead to a review being submitted has been declining steadily for four of the six
      journals examined here, but reviewer fatigue is not likely the primary
      explanation for this decline.

PMID- 29451534
TI  - Simple decision-tree tool to facilitate author identification of reporting
      guidelines during submission: a before-after study.
AB  - Background: There is evidence that direct journal endorsement of reporting
      guidelines can lead to important improvements in the quality and reliability of
      the published research. However, over the last 20 years, there has been a
      proliferation of reporting guidelines for different study designs, making it
      impractical for a journal to explicitly endorse them all. The objective of this
      study was to investigate whether a decision tree tool made available during the
      submission process facilitates author identification of the relevant reporting
      guideline. Methods: This was a prospective 14-week before-after study across four
      speciality medical research journals. During the submission process, authors were
      prompted to follow the relevant reporting guideline from the EQUATOR Network and
      asked to confirm that they followed the guideline ('before'). After 7 weeks, this
      prompt was updated to include a direct link to the decision-tree tool and an
      additional prompt for those authors who stated that 'no guidelines were
      applicable' ('after'). For each article submitted, the authors' response, what
      guideline they followed (if any) and what reporting guideline they should have
      followed (including none relevant) were recorded. Results: Overall, 590
      manuscripts were included in this analysis-300 in the before cohort and 290 in
      the after. There were relevant reporting guidelines for 75% of manuscripts in
      each group; STROBE was the most commonly applicable reporting guideline, relevant
      for 35% (n = 106) and 37% (n = 106) of manuscripts, respectively. Use of the tool
      was associated with an 8.4% improvement in the number of authors correctly
      identifying the relevant reporting guideline for their study (p < 0.0001), a 14%
      reduction in the number of authors incorrectly stating that there were no
      relevant reporting guidelines (p < 0.0001), and a 1.7% reduction in authors
      choosing a guideline (p = 0.10). However, the 'after' cohort also saw a
      significant increase in the number of authors stating that there were relevant
      reporting guidelines for their study, but not specifying which (34 vs 29%; p =
      0.04). Conclusion: This study suggests that use of a decision-tree tool during
      submission of a manuscript is associated with improved author identification of
      the relevant reporting guidelines for their study type; however, the majority of
      authors still failed to correctly identify the relevant guidelines.

PMID- 29451535
TI  - Updating standards for reporting diagnostic accuracy: the development of STARD
      2015.
AB  - Background: Although the number of reporting guidelines has grown rapidly, few
      have gone through an updating process. The STARD statement (Standards for
      Reporting Diagnostic Accuracy), published in 2003 to help improve the
      transparency and completeness of reporting of diagnostic accuracy studies, was
      recently updated in a systematic way. Here, we describe the steps taken and a
      justification for the changes made. Results: A 4-member Project Team coordinated
      the updating process; a 14-member Steering Committee was regularly solicited by
      the Project Team when making critical decisions. First, a review of the
      literature was performed to identify topics and items potentially relevant to the
      STARD updating process. After this, the 85 members of the STARD Group were
      invited to participate in two online surveys to identify items that needed to be
      modified, removed from, or added to the STARD checklist. Based on the results of
      the literature review process, 33 items were presented to the STARD Group in the
      online survey: 25 original items and 8 new items; 73 STARD Group members (86 %)
      completed the first survey, and 79 STARD Group members (93 %) completed the
      second survey.Then, an in-person consensus meeting was organized among the
      members of the Project Team and Steering Committee to develop a consensual draft
      version of STARD 2015. This version was piloted in three rounds among a total of
      32 expert and non-expert users. Piloting mostly led to rewording of items. After
      this, the update was finalized. The updated STARD 2015 list now consists of 30
      items. Compared to the previous version of STARD, three original items were each
      converted into two new items, four original items were incorporated into other
      items, and seven new items were added. Conclusions: After a systematic updating
      process, STARD 2015 provides an updated list of 30 essential items for reporting
      diagnostic accuracy studies.

PMID- 29451536
TI  - Percentage-based Author Contribution Index: a universal measure of author
      contribution to scientific articles.
AB  - Background: Deciphering the amount of work provided by different co-authors of a
      scientific paper has been a recurrent problem in science. Despite the myriad of
      metrics available, the scientific community still largely relies on the position
      in the list of authors to evaluate contributions, a metric that attributes
      subjective and unfounded credit to co-authors. We propose an easy to apply,
      universally comparable and fair metric to measure and report co-authors
      contribution in the scientific literature. Methods: The proposed Author
      Contribution Index (ACI) is based on contribution percentages provided by the
      authors, preferably at the time of submission. Researchers can use ACI to compare
      the contributions of different authors, describe the contribution profile of a
      particular researcher or analyse how contribution changes through time. We
      provide such an analysis based on contribution percentages provided by 97
      scientists from the field of ecology who voluntarily responded to an online
      anonymous survey. Results: ACI is simple to understand and to implement because
      it is based solely on percentage contributions and the number of co-authors. It
      provides a continuous score that reflects the contribution of one author as
      compared to the average contribution of all other authors. For example, ACI(i) =
      3, means that author i contributed three times more than what the other authors
      contributed on average. Our analysis comprised 836 papers published in 2014-2016
      and revealed patterns of ACI values that relate to career advancement.
      Conclusion: There are many examples of author contribution indices that have been
      proposed but none has really been adopted by scientific journals. Many of the
      proposed solutions are either too complicated, not accurate enough or not
      comparable across articles, authors and disciplines. The author contribution
      index presented here addresses these three major issues and has the potential to
      contribute to more transparency in the science literature. If adopted by
      scientific journals, it could provide job seekers, recruiters and evaluating
      bodies with a tool to gather information that is essential to them and cannot be
      easily and accurately obtained otherwise. We also suggest that scientists use the
      index regardless of whether it is implemented by journals or not.

PMID- 29451537
TI  - Improving the process of research ethics review.
AB  - Background: Research Ethics Boards, or Institutional Review Boards, protect the
      safety and welfare of human research participants. These bodies are responsible
      for providing an independent evaluation of proposed research studies, ultimately
      ensuring that the research does not proceed unless standards and regulations are
      met. Main body: Concurrent with the growing volume of human participant research,
      the workload and responsibilities of Research Ethics Boards (REBs) have continued
      to increase. Dissatisfaction with the review process, particularly the time
      interval from submission to decision, is common within the research community,
      but there has been little systematic effort to examine REB processes that may
      contribute to inefficiencies. We offer a model illustrating REB workflow,
      stakeholders, and accountabilities. Conclusion: Better understanding of the
      components of the research ethics review will allow performance targets to be
      set, problems identified, and solutions developed, ultimately improving the
      process.

PMID- 29451538
TI  - MRI spot sign.

PMID- 29451539
TI  - CORRIGENDUM FOR "Coxsackievirus-Induced Proteomic Alterations in Primary Human
      Islets Provide Insights for the Etiology of Diabetes".
AB  - [This corrects the article DOI: 10.1210/js.2017-00278.].

PMID- 29451540
TI  - Developing the Clarity and Openness in Reporting: E3-based (CORE) Reference user
      manual for creation of clinical study reports in the era of clinical trial
      transparency.
AB  - Background: Interventional clinical studies conducted in the regulated drug
      research environment are reported using International Council for Harmonisation
      (ICH) regulatory guidance documents: ICH E3 on the structure and content of
      clinical study reports (CSRs) published in 1995 and ICH E3 supplementary
      Questions & Answers (Q & A) published in 2012.Since the ICH guidance documents
      were published, there has been heightened awareness of the importance of
      disclosure of clinical study results. The use of the CSR as a key source document
      to fulfil emerging obligations has resulted in a re-examination of how ICH
      guidelines are applied in CSR preparation. The dynamic regulatory and modern drug
      development environments create emerging reporting challenges. Methods:
      Regulatory medical writing and statistical professionals developed Clarity and
      Openness in Reporting: E3-based (CORE) Reference over a 2-year period.
      Stakeholders contributing expertise included a global industry association,
      regulatory agency, patient advocate, academic and Principal Investigator
      representatives. Results: CORE Reference should help authors navigate relevant
      guidelines as they create CSR content relevant for today's studies. It offers
      practical suggestions for developing CSRs that will require minimum redaction and
      modification prior to public disclosure.CORE Reference comprises a Preface,
      followed by the actual resource. The Preface clarifies intended use and
      underlying principles that inform resource utility. The Preface lists references
      contributing to development of the resource, which broadly fall into 'regulatory'
      and 'public disclosure' categories. The resource includes ICH E3 guidance text,
      ICH E3 Q & A 2012-derived guidance text and CORE Reference text, distinguished
      from one another through the use of shading. Rationale comments are used
      throughout for clarification purposes.A separate mapping tool comparing ICH E3
      sectional structure and CORE Reference sectional structure is also
      provided.Together, CORE Reference and the mapping tool constitute the user
      manual. Conclusions: This publication is intended to enhance the use,
      understanding and dissemination of CORE Reference.The CORE Reference user manual
      and the associated website (http://www.core-reference.org) should improve the
      reporting of interventional clinical studies.Periodic updates of CORE Reference
      are planned to maintain its relevance. Registration: CORE Reference was
      registered with http://www.equator-network.org on 23 March 2015.

PMID- 29451541
TI  - Publishing descriptions of non-public clinical datasets: proposed guidance for
      researchers, repositories, editors and funding organisations.
AB  - Sharing of experimental clinical research data usually happens between
      individuals or research groups rather than via public repositories, in part due
      to the need to protect research participant privacy. This approach to data
      sharing makes it difficult to connect journal articles with their underlying
      datasets and is often insufficient for ensuring access to data in the long term.
      Voluntary data sharing services such as the Yale Open Data Access (YODA) and
      Clinical Study Data Request (CSDR) projects have increased accessibility to
      clinical datasets for secondary uses while protecting patient privacy and the
      legitimacy of secondary analyses but these resources are generally disconnected
      from journal articles-where researchers typically search for reliable information
      to inform future research. New scholarly journal and article types dedicated to
      increasing accessibility of research data have emerged in recent years and, in
      general, journals are developing stronger links with data repositories. There is
      a need for increased collaboration between journals, data repositories,
      researchers, funders, and voluntary data sharing services to increase the
      visibility and reliability of clinical research. Using the journal Scientific
      Data as a case study, we propose and show examples of changes to the format and
      peer-review process for journal articles to more robustly link them to data that
      are only available on request. We also propose additional features for data
      repositories to better accommodate non-public clinical datasets, including Data
      Use Agreements (DUAs).

PMID- 29451542
TI  - Propagation of errors in citation networks: a study involving the entire citation
      network of a widely cited paper published in, and later retracted from, the
      journal Nature.
AB  - Background: In about one in 10,000 cases, a published article is retracted. This
      very often means that the results it reports are flawed. Several authors have
      voiced concerns about the presence of retracted research in the memory of
      science. In particular, a retracted result is propagated by citing it. In the
      published literature, many instances are given of retracted articles that are
      cited both before and after their retraction. Even worse is the possibility that
      these articles in turn are cited in such a way that the retracted result is
      propagated further. Methods: We have conducted a case study to find out how a
      retracted article is cited and whether retracted results are propagated through
      indirect citations. We have constructed the entire citation network for this
      case. Results: We show that directly citing articles is an important source of
      propagation of retracted research results. In contrast, in our case study,
      indirect citations do not contribute to the propagation of the retracted result.
      Conclusions: While admitting the limitations of a study involving a single case,
      we think there are reasons for the non-contribution of indirect citations that
      hold beyond our case study.

PMID- 29451543
TI  - Sex and Gender Equity in Research: rationale for the SAGER guidelines and
      recommended use.
AB  - Background: Sex and gender differences are often overlooked in research design,
      study implementation and scientific reporting, as well as in general science
      communication. This oversight limits the generalizability of research findings
      and their applicability to clinical practice, in particular for women but also
      for men. This article describes the rationale for an international set of
      guidelines to encourage a more systematic approach to the reporting of sex and
      gender in research across disciplines. Methods: A panel of 13 experts
      representing nine countries developed the guidelines through a series of
      teleconferences, conference presentations and a 2-day workshop. An internet
      survey of 716 journal editors, scientists and other members of the international
      publishing community was conducted as well as a literature search on sex and
      gender policies in scientific publishing. Results: The Sex and Gender Equity in
      Research (SAGER) guidelines are a comprehensive procedure for reporting of sex
      and gender information in study design, data analyses, results and interpretation
      of findings. Conclusions: The SAGER guidelines are designed primarily to guide
      authors in preparing their manuscripts, but they are also useful for editors, as
      gatekeepers of science, to integrate assessment of sex and gender into all
      manuscripts as an integral part of the editorial process.

PMID- 29451544
TI  - A new forum for research on research integrity and peer review.
AB  - This editorial explains why we are launching Research Integrity and Peer Review,
      a new open-access journal that will provide a home to research on ethics,
      reporting, and evaluation of research. We discuss how the idea to launch this
      journal came about and identify the gaps in knowledge where we would like to
      encourage more research and interdisciplinary discussion. We are particularly
      keen to receive submissions presenting actual research that will increase our
      understanding and suggest potential solutions to issues related to peer review,
      study reporting, and research and publication ethics.

PMID- 29451545
TI  - Text recycling in health sciences research literature: a rhetorical perspective.
AB  - The past few years have seen a steady rise in the number of health science
      journals using plagiarism detection software to screen submitted manuscripts.
      While there is widespread agreement about the need to guard against plagiarism
      and duplicate publication, the use of such tools has sparked debate about text
      recycling-the reuse of material from one's prior publications in a new
      manuscript. Many who have published on the topic consider all uses of text
      recycling anathema. Others argue that some uses of recycling are unavoidable and
      sometimes even beneficial for readers. Unfortunately, much of this discourse now
      merely repeats dogmatic assertions. I argue that progress can be made by
      acknowledging three points: First, citation standards for research writing in the
      health sciences will not mirror those of the humanities. Second, while it is
      impossible to draw a definitive line between appropriate and inappropriate uses
      of text recycling, some uses of the practice lie clearly on the legitimate side.
      Third, the needs of editors for information regarding recycled text are different
      from those of readers. Ultimately, calls for rewording and citation as
      alternatives or fixes for text recycling are unlikely to prove satisfactory to
      either readers or editors. A response to this article can be found using the
      following link:
      http://researchintegrityjournal.biomedcentral.com/articles/10.1186/s41073-017
      0026-y.

PMID- 29451546
TI  - The high costs of getting ethical and site-specific approvals for multi-centre
      research.
AB  - Background: Multi-centre studies generally cost more than single-centre studies
      because of larger sample sizes and the need for multiple ethical approvals. Multi
      centre studies include clinical trials, clinical quality registries,
      observational studies and implementation studies. We examined the costs of two
      large Australian multi-centre studies in obtaining ethical and site-specific
      approvals. Methods: We collected data on staff time spent on approvals and
      expressed the overall cost as a percent of the total budget. Results: The total
      costs of gaining approval were 38 % of the budget for a study of 50 centres (mean
      cost AUD $6960 per site) and 2 % for a study of 11 centres (mean cost AUD $2300
      per site). Seventy-five and 90 % of time was spent on repeated tasks,
      respectively, and many time-consuming tasks, such as reformatting documents, did
      nothing to improve the study design or participant safety. Conclusions:
      Improvements have been made to the ethical approval application system, but more
      gains could be made without increasing risks of harm to research participants. We
      propose that ethical review bodies and individual sites publish statistics on how
      long they take to process approvals which could then be nationally benchmarked.

PMID- 29451548
TI  - 'Are you siding with a personality or the grant proposal?': observations on how
      peer review panels function.
AB  - Background: In Australia, the peer review process for competitive funding is
      usually conducted by a peer review group in conjunction with prior assessment
      from external assessors. This process is quite mysterious to those outside it.
      The purpose of this research was to throw light on grant review panels (sometimes
      called the 'black box') through an examination of the impact of panel procedures,
      panel composition and panel dynamics on the decision-making in the grant review
      process. A further purpose was to compare experience of a simplified review
      process with more conventional processes used in assessing grant proposals in
      Australia. Methods: This project was one aspect of a larger study into the costs
      and benefits of a simplified peer review process. The Queensland University of
      Technology (QUT)-simplified process was compared with the National Health and
      Medical Research Council's (NHMRC) more complex process. Grant review panellists
      involved in both processes were interviewed about their experience of the
      decision-making process that assesses the excellence of an application. All
      interviews were recorded and transcribed. Each transcription was de-identified
      and returned to the respondent for review. Final transcripts were read repeatedly
      and coded, and similar codes were amalgamated into categories that were used to
      build themes. Final themes were shared with the research team for feedback.
      Results: Two major themes arose from the research: (1) assessing grant proposals
      and (2) factors influencing the fairness, integrity and objectivity of review.
      Issues such as the quality of writing in a grant proposal, comparison of the two
      review methods, the purpose and use of the rebuttal, assessing the financial
      value of funded projects, the importance of the experience of the panel
      membership and the role of track record and the impact of group dynamics on the
      review process were all discussed. The research also examined the influence of
      research culture on decision-making in grant review panels. One of the aims of
      this study was to compare a simplified review process with more conventional
      processes. Generally, participants were supportive of the simplified process.
      Conclusions: Transparency in the grant review process will result in better
      appreciation of the outcome. Despite the provision of clear guidelines for peer
      review, reviewing processes are likely to be subjective to the extent that
      different reviewers apply different rules. The peer review process will come
      under more scrutiny as funding for research becomes even more competitive. There
      is justification for further research on the process, especially of a kind that
      taps more deeply into the 'black box' of peer review.

PMID- 29451547
TI  - Selective citation in the literature on swimming in chlorinated water and
      childhood asthma: a network analysis.
AB  - Background: Knowledge development depends on an unbiased representation of the
      available evidence. Selective citation may distort this representation. Recently,
      some controversy emerged regarding the possible impact of swimming on childhood
      asthma, raising the question about the role of selective citation in this field.
      Our objective was to assess the occurrence and determinants of selective citation
      in scientific publications on the relationship between swimming in chlorinated
      pools and childhood asthma. Methods: We identified scientific journal articles on
      this relationship via a systematic literature search. The following factors were
      taken into account: study outcome (authors' conclusion, data-based conclusion),
      other content-related article characteristics (article type, sample size,
      research quality, specificity), content-unrelated article characteristics
      (language, publication title, funding source, number of authors, number of
      affiliations, number of references, journal impact factor), author
      characteristics (gender, country, affiliation), and citation characteristics
      (time to citation, authority, self-citation). To assess the impact of these
      factors on citation, we performed a series of univariate and adjusted random
      effects logistic regressions, with potential citation path as unit of analysis.
      Results: Thirty-six articles were identified in this network, consisting of 570
      potential citation paths of which 191 (34%) were realized. There was strong
      evidence that articles with at least one author in common, cited each other more
      often than articles that had no common authors (odds ratio (OR) 5.2, 95%
      confidence interval (CI) 3.1-8.8). Similarly, the chance of being cited was
      higher for articles that were empirical rather than narrative (OR 4.2, CI 2.6
      6.7), that reported a large sample size (OR 5.8, CI 2.9-11.6), and that were
      written by authors with a high authority within the network (OR 4.1, CI 2.1-8.0).
      Further, there was some evidence for citation bias: articles that confirmed the
      relation between swimming and asthma were cited more often (OR 1.8, CI 1.1-2.9),
      but this finding was not robust. Conclusions: There is clear evidence of
      selective citation in this research field, but the evidence for citation bias is
      not very strong.

PMID- 29451549
TI  - Retractions in cancer research: a systematic survey.
AB  - Background: The annual number of retracted publications in the scientific
      literature is rapidly increasing. The objective of this study was to determine
      the frequency and reason for retraction of cancer publications and to determine
      how journals in the cancer field handle retracted articles. Methods: We searched
      three online databases (MEDLINE, Embase, The Cochrane Library) from database
      inception until 2015 for retracted journal publications related to cancer
      research. For each article, the reason for retraction was categorized as
      plagiarism, duplicate publication, fraud, error, authorship issues, or ethical
      issues. Accessibility of the retracted article was defined as intact, removed, or
      available but with a watermark over each page. Descriptive data was collected on
      each retracted article including number of citations, journal name and impact
      factor, study design, and time between publication and retraction. The
      publications were screened in duplicated and two reviewers extracted and
      categorized data. Results: Following database search and article screening, we
      identified 571 retracted cancer publications. The majority (76.4%) of cancer
      retractions were issued in the most recent decade, with 16.6 and 6.7% of the
      retractions in the prior two decades respectively. Retractions were issued by
      journals with impact factors ranging from 0 (discontinued) to 55.8. The average
      impact factor was 5.4 (median 3.54, IQR 1.8-5.5). On average, a retracted article
      was cited 45 times (median 18, IQR 6-51), with a range of 0-742. Reasons for
      retraction include plagiarism (14.4%), fraud (28.4%), duplicate publication
      (18.2%), error (24.2%), authorship issues (3.9%), and ethical issues (2.1%). The
      reason for retraction was not stated in 9.8% of cases. Twenty-nine percent of
      retracted articles remain available online in their original form. Conclusions:
      Retractions in cancer research are increasing in frequency at a similar rate to
      all biomedical research retractions. Cancer retractions are largely due to
      academic misconduct. Consequences to cancer patients, the public at large, and
      the research community can be substantial and should be addressed with future
      research. Despite the implications of this important issue, some cancer journals
      currently fall short of the current guidelines for clearly stating the reason for
      retraction and identifying the publication as retracted.

PMID- 29451550
TI  - Do peer review models affect clinicians' trust in journals? A survey of junior
      doctors.
AB  - Background: The aim of this survey was to determine the level of awareness and
      understanding of peer review and peer review models amongst junior hospital
      doctors and whether this influences clinical decision-making. Methods: A 30
      question online anonymous survey was developed aimed at determining awareness of
      peer review models and the purpose of peer review, perceived trustworthiness of
      different peer review models and the role of peer review in clinical decision
      making. It was sent to 800 trainee doctors in medical specialties on the
      University College London Partners trainee database. Results: The response rate
      was (178/800) 22%. Most respondents were specialist registrars. Checking that
      research is conducted correctly (152/178, 85%) and the data interpreted correctly
      (148/178, 83%) were viewed as the most important purposes of peer review. Most
      respondents were aware of open (133/178, 75%), double-blind (125/178, 70%) and
      single-blind peer review (121/178, 68%). 101/178 (57%) had heard of
      collaborative, 87/178 (49%) of post publication and 29/178 (16%) of decoupled
      peer review. Of those who were aware of double-blind, single-blind open and
      collaborative peer review, 85 (68%), 82 (68%), 74 (56%) and 24 (24%),
      respectively, understood how they worked. The NEJM, Lancet and The BMJ were
      deemed to have most trustworthy peer review, 137/178 (77%), 129/178 (72%) and
      115/178 (65%), respectively. That peer review had taken place was important for a
      journal content to be used for clinical decision-making 152/178 (85%), but the
      ability to see peer review reports was not as important 22/178 (12%). Most felt
      there was a need for peer review training and that this should be at the
      specialist registrar stage of training. Conclusions: Junior hospital doctors view
      peer review to be important as a means of quality control, but do not value the
      ability to scrutinize peer review themselves. The unquestioning acceptance of
      peer review as final validation in the field of medicine emphasises not only the
      responsibility held by medical journals to ensure peer review is done well but
      also the need to raise awareness amongst the medical community of the limitations
      of the current peer review process.

PMID- 29451551
TI  - Ranking major and minor research misbehaviors: results from a survey among
      participants of four World Conferences on Research Integrity.
AB  - Background: Codes of conduct mainly focus on research misconduct that takes the
      form of fabrication, falsification, and plagiarism. However, at the aggregate
      level, lesser forms of research misbehavior may be more important due to their
      much higher prevalence. Little is known about what the most frequent research
      misbehaviors are and what their impact is if they occur. Methods: A survey was
      conducted among 1353 attendees of international research integrity conferences.
      They were asked to score 60 research misbehaviors according to their views on and
      perceptions of the frequency of occurrence, preventability, impact on truth
      (validity), and impact on trust between scientists on 5-point scales. We
      expressed the aggregate level impact as the product of frequency scores and
      truth, trust and preventability scores, respectively. We ranked misbehaviors
      based on mean scores. Additionally, relevant demographic and professional
      background information was collected from participants. Results: Response was 17%
      of those who were sent the invitational email and 33% of those who opened it. The
      rankings suggest that selective reporting, selective citing, and flaws in quality
      assurance and mentoring are viewed as the major problems of modern research. The
      "deadly sins" of fabrication and falsification ranked highest on the impact on
      truth but low to moderate on aggregate level impact on truth, due to their low
      estimated frequency. Plagiarism is thought to be common but to have little impact
      on truth although it ranked high on aggregate level impact on trust. Conclusions:
      We designed a comprehensive list of 60 major and minor research misbehaviors. Our
      respondents were much more concerned over sloppy science than about scientific
      fraud (FFP). In the fostering of responsible conduct of research, we recommend to
      develop interventions that actively discourage the high ranking misbehaviors from
      our study.

PMID- 29451552
TI  - Plagiarism in submitted manuscripts: incidence, characteristics and optimization
      of screening-case study in a major specialty medical journal.
AB  - Background: Plagiarism is common and threatens the integrity of the scientific
      literature. However, its detection is time consuming and difficult, presenting
      challenges to editors and publishers who are entrusted with ensuring the
      integrity of published literature. Methods: In this study, the extent of
      plagiarism in manuscripts submitted to a major specialty medical journal was
      documented. We manually curated submitted manuscripts and deemed an article
      contained plagiarism if one sentence had 80 % of the words copied from another
      published paper. Commercial plagiarism detection software was utilized and its
      use was optimized. Results: In 400 consecutively submitted manuscripts, 17 % of
      submissions contained unacceptable levels of plagiarized material with 82 % of
      plagiarized manuscripts submitted from countries where English was not an
      official language. Using the most commonly employed commercial plagiarism
      detection software, sensitivity and specificity were studied with regard to the
      generated plagiarism score. The cutoff score maximizing both sensitivity and
      specificity was 15 % (sensitivity 84.8 % and specificity 80.5 %). Conclusions:
      Plagiarism was a common occurrence among manuscripts submitted for publication to
      a major American specialty medical journal and most manuscripts with plagiarized
      material were submitted from countries in which English was not an official
      language. The use of commercial plagiarism detection software can be optimized by
      selecting a cutoff score that reflects desired sensitivity and specificity.

PMID- 29451553
TI  - Registration of randomized controlled trials in nursing journals.
AB  - Background: Trial registration helps minimize publication and reporting bias. In
      leading medical journals, 96% of published trials are registered. The aim of this
      study was to determine the proportion of randomized controlled trials published
      in key nursing journals that met criteria for timely registration. Methods: We
      reviewed all RCTs published in three (two general, one mental health) nursing
      journals between August 2011 and September 2016. We classified the included
      trials as: 1. Not registered, 2. Registered but not reported in manuscript, 3.
      Registered retrospectively, 4. Registered prospectively (before the recruitment
      of the first subject into the trial). 5. Timely registration (as 4 but the trial
      identification number is reported in abstract). Results: We identified 135 trials
      published in the three included journals. The majority (n = 78, 58%) were not
      registered. Thirty-three (24%) were retrospectively registered. Of the 24 (18%)
      trials that were prospectively registered, 11 (8%) met the criteria for timely
      registration. Conclusions: There is an unacceptable difference in rates of trial
      registration between leading medical and nursing journals. Concerted effort is
      required by nurse researchers, reviewers and journal editors to ensure that all
      trials are registered in a timely way.

PMID- 29451554
TI  - Is it becoming harder to secure reviewers for peer review? A test with data from
      five ecology journals.
AB  - Background: There is concern in the academic publishing community that it is
      becoming more difficult to secure reviews for peer-reviewed manuscripts, but much
      of this concern stems from anecdotal and rhetorical evidence. Methods: We
      examined the proportion of review requests that led to a completed review over a
      6-year period (2009-2015) in a mid-tier biology journal (Molecular Ecology). We
      also re-analyzed previously published data from four other mid-tier ecology
      journals (Functional Ecology, Journal of Ecology, Journal of Animal Ecology, and
      Journal of Applied Ecology), looking at the same proportion over the period 2003
      to 2010. Results: The data from Molecular Ecology showed no significant decrease
      through time in the proportion of requests that led to a review (proportion in
      2009 = 0.47 (95 % CI = 0.43 to 0.52), proportion in 2015 = 0.44 (95 % CI = 0.40
      to 0.48)). This proportion did decrease for three of the other ecology journals
      (changes in proportions from 2003 to 2010 = -0.10, -0.18, and -0.09), while the
      proportion for the fourth (Functional Ecology) stayed roughly constant (change in
      proportion = -0.04). Conclusions: Overall, our data suggest that reviewer
      agreement rates have probably declined slightly but not to the extent suggested
      by the anecdotal and rhetorical evidence.

PMID- 29451555
TI  - Mentored peer review of standardized manuscripts as a teaching tool for
      residents: a pilot randomized controlled multi-center study.
AB  - Background: There is increasing need for peer reviewers as the scientific
      literature grows. Formal education in biostatistics and research methodology
      during residency training is lacking. In this pilot study, we addressed these
      issues by evaluating a novel method of teaching residents about biostatistics and
      research methodology using peer review of standardized manuscripts. We
      hypothesized that mentored peer review would improve resident knowledge and
      perception of these concepts more than non-mentored peer review, while improving
      review quality. Methods: A partially blinded, randomized, controlled multi-center
      study was performed. Seventy-eight neurology residents from nine US neurology
      programs were randomized to receive mentoring from a local faculty member or not.
      Within a year, residents reviewed a baseline manuscript and four subsequent
      manuscripts, all with introduced errors designed to teach fundamental review
      concepts. In the mentored group, mentors discussed completed reviews with
      residents. Primary outcome measure was change in knowledge score between pre- and
      post-tests, measuring epidemiology and biostatistics knowledge. Secondary outcome
      measures included level of confidence in the use and interpretation of
      statistical concepts before and after intervention, and RQI score for baseline
      and final manuscripts. Results: Sixty-four residents (82%) completed initial
      review with gradual decline in completion on subsequent reviews. Change in
      primary outcome, the difference between pre- and post-test knowledge scores, did
      not differ between mentored (-8.5%) and non-mentored (-13.9%) residents (p =
      0.48). Significant differences in secondary outcomes (using 5-point Likert scale,
      5 = strongly agree) included mentored residents reporting enhanced understanding
      of research methodology (3.69 vs 2.61; p = 0.001), understanding of manuscripts
      (3.73 vs 2.87; p = 0.006), and application of study results to clinical practice
      (3.65 vs 2.78; p = 0.005) compared to non-mentored residents. There was no
      difference between groups in level of interest in peer review (3.00 vs 3.09; p =
      0.72) or the quality of manuscript review assessed by the Review Quality
      Instrument (RQI) (3.25 vs 3.06; p = 0.50). Conclusions: We used mentored peer
      review of standardized manuscripts to teach biostatistics and research
      methodology and introduce the peer review process to residents. Though knowledge
      level did not change, mentored residents had enhanced perception in their
      abilities to understand research methodology and manuscripts and apply study
      results to clinical practice.

PMID- 29451556
TI  - Factors associated with online media attention to research: a cohort study of
      articles evaluating cancer treatments.
AB  - Background: New metrics have been developed to assess the impact of research and
      provide an indication of online media attention and data dissemination. We aimed
      to describe online media attention of articles evaluating cancer treatments and
      identify the factors associated with high online media attention. Methods: We
      systematically searched MEDLINE via PubMed on March 1, 2015 for articles
      published during the first 6 months of 2014 in oncology and medical journals with
      a diverse range of impact factors, from 3.9 to 54.4, and selected a sample of
      articles evaluating a cancer treatment regardless of study design. Altmetric
      Explorer was used to identify online media attention of selected articles. The
      primary outcome was media attention an article received online as measured by
      Altmetric score (i.e., number of mentions in online news outlets, science blogs
      and social media). Regression analysis was performed to investigate the factors
      associated with high media attention, and regression coefficients represent the
      logarithm of ratio of mean (RoM) values of Altmetric score per unit change in the
      covariate. Results: Among 792 articles, 218 (27.5%) received no online media
      attention (Altmetric score = 0). The median [Q1-Q3] Altmetric score was 2.0 [0.0
      8.0], range 0.0-428.0. On multivariate analysis, factors associated with high
      Altmetric score were presence of a press release (RoM = 10.14, 95%CI [4.91
      20.96]), open access to the article (RoM = 1.48, 95%CI [1.02-2.16]), and journal
      impact factor (RoM = 1.10, 95%CI [1.07-1.12]. As compared with observational
      studies, systematic reviews were not associated with high Altmetric score (RoM =
      1.46, 95%CI [0.74-2.86]; P = 0.27), nor were RCTs (RoM = 0.65, 95%CI [0.41-1.02];
      P = 0.059) and phase I/II non-RCTs (RoM = 0.58, 95%CI [0.33-1.05]; P = 0.07). The
      articles with abstract conclusions favouring study treatments were not associated
      with high Altmetric score (RoM = 0.97, 95%CI [0.60-1.58]; P = 0.91). Conclusions:
      Most important factors associated with high online media attention were the
      presence of a press release and the journal impact factor. There was no evidence
      that study design with high level of evidence and type of abstract conclusion
      were associated with high online media attention.

PMID- 29451557
TI  - Biomedical journal speed and efficiency: a cross-sectional pilot survey of author
      experiences.
AB  - Background: Although the peer review process is believed to ensure scientific
      rigor, enhance research quality, and improve manuscript clarity, many
      investigators are concerned that the process is too slow, too expensive, too
      unreliable, and too static. In this feasibility study, we sought to survey
      corresponding authors of recently published clinical research studies on the
      speed and efficiency of the publication process. Methods: Web-based survey of
      corresponding authors of a 20% random sample of clinical research studies in
      MEDLINE-indexed journals with Ovid MEDLINE entry dates between December 1 and 15,
      2016. Survey addressed perceived manuscript importance before first submission,
      approximate first submission and final acceptance dates, and total number of
      journal submissions, external peer reviews, external peer reviewers, and
      revisions requested, as well as whether authors would have considered publicly
      sharing their manuscript on an online platform instead of submitting to a peer
      reviewed journal. Results: Of 1780 surveys distributed, 27 corresponding authors
      opted out or requested that we stop emailing them and 149 emails failed (e.g.,
      emails that bounced n = 64, returned with an away from office message n = 70, or
      were changed/incorrect n = 15), leaving 1604 respondents, of which 337 completed
      the survey (21.0%). Respondents and non-respondents were similar with respect to
      study type and publication journals' impact factor, although non-respondent
      authors had more publications (p = 0.03). Among respondents, the median impact
      factor of the publications' journal was 2.7 (interquartile range (IQR), 2.0-3.6)
      and corresponding authors' median h-index and number of publications was 9 (IQR,
      3-20) and 27 (IQR, 10-77), respectively. The median time from first submission to
      journal acceptance and publication was 5 months (IQR, 3-8) and 7 months (IQR, 5
      12), respectively. Most respondents (62.0%, n = 209) rated the importance of
      their research as a 4 or 5 (5-point scale) prior to submission. Median number of
      journal submissions was 1 (IQR, 1-2), external peer reviews was 1 (IQR, 1-2),
      external peer reviewers was 3 (IQR, 2-4), and revisions requested was 1 (IQR, 1
      1). Sharing manuscripts to a public online platform, instead of submitting to a
      peer-reviewed journal, would have been considered by 55.2% (n = 186) of
      respondents. Conclusion: Corresponding authors have high perceptions of their
      research and reported requiring few manuscript submissions prior to journal
      acceptance, most commonly by lower impact factor journals.

PMID- 29451558
TI  - Do declarative titles affect readers' perceptions of research findings? A
      randomized trial.
AB  - Background: Many journals prohibit the use of declarative titles that state study
      findings, yet a few journals encourage or even require them. We compared the
      effects of a declarative versus a descriptive title on readers' perceptions about
      the strength of evidence in a research abstract describing a randomized trial.
      Methods: Study participants (medical or dental students or doctors attending
      lectures) read two abstracts describing studies of a fictitious treatment
      (Anticox) for a fictitious condition (Green's syndrome). The first abstract (A1)
      described an uncontrolled, 10-patient, case series, and the second (A2) described
      a randomized, placebo-controlled trial involving 48 patients. All participants
      rated identical A1 abstracts (with a descriptive title) to provide baseline
      ratings and thus reduce the effects of inter-individual variability. Participants
      were randomized so that half rated a version of A2 with a descriptive title and
      half with a declarative title. For each abstract, participants indicated their
      agreement with the statement "Anticox is an effective treatment for pain in
      Green's syndrome" using 100 mm visual analogue scales (VAS) ranging from
      "disagree completely" to "agree completely." VAS scores were measured by an
      investigator who was unaware of group allocation. Results: One hundred forty-four
      participants from four centres completed the study. There was no significant
      difference between the declarative and the descriptive title groups' confidence
      in the study conclusions as expressed on VAS scales-in fact, the mean difference
      between A1 and A2 was smaller for the declarative title group than that for the
      descriptive title group (32.6 mm, SD 27.4 vs. 39.8 mm, SD 22.6, respectively, p =
      0.09). Conclusions: We found no evidence that the use of a declarative title
      affected readers' perceptions about study conclusions. This suggests that
      editors' fears that declarative titles might unduly influence readers' judgements
      about study conclusions may be unfounded, at least in relation to reports of
      randomized trials. However, our study design had several limitations, and our
      findings may not be generalizable to other situations.

PMID- 29451559
TI  - Linking chromatin dynamics, cell fate plasticity, and tissue homeostasis in adult
      mouse hair follicle stem cells.
AB  - Cellular plasticity for fate acquisition is associated with distinct chromatin
      states, which include histone modifications, dynamic association of chromatin
      factors with the DNA, and global chromatin compaction and nuclear organization.
      While embryonic stem cell (ESC) plasticity in vitro and its link with chromatin
      states have been characterized in depth, little is known about tissue stem cell
      plasticity in vivo, during adult tissue homeostasis. Recently, we reported a
      distinct globally low level of histone H3 K4/9/27me3 in mouse hair follicle stem
      cells (HFSCs) during quiescence. This occurred at the stage preceding fate
      acquisition, when HFSC fate plasticity must be at its highest. This
      hypomethylated state was required for proper skin homeostasis and timely hair
      cycle. Here, we show both in the live tissue and in cell culture that at
      quiescence HFSCs have higher exchange rates for core histone H2B when compared
      with proliferative or differentiated cells. This denoted a hyperdynamic chromatin
      state, which was previously associated with high cell fate plasticity in ESCs.
      Moreover, we find that quiescent HFSCs display a higher propensity for de
      differentiation in response to Yamanaka's reprogramming factors in vivo. These
      results further support our recent model in which HFSCs render their chromatin
      into a specific state at quiescence, which is attuned to higher cell fate
      plasticity.

PMID- 29451560
TI  - Long noncoding RNAs and their roles in skeletal muscle fate determination.
AB  - Myogenic fate determination is important in skeletal muscle development, growth
      and repair. A variety of factors regulate myogenic cell determination via
      transcriptional and non-transcriptional mechanisms. Amongst these factors, long
      noncoding RNAs (lncRNAs) have gained considerable attention for their important
      roles in regulating myogenic differentiation and function. Many classes of
      lncRNAs have been discovered; various lncRNAs have been implicated in the
      regulation of myogenic cell fate determination and are the subject of this brief
      review.

PMID- 29451562
TI  - Comment on Cary Moskovitz' "Text Recycling in Health Sciences Literature: A
      Rhetorical Perspective".
AB  - The question of covert text recycling from previous publications is discussed. It
      is argued that, consistent with current guidance, authors may be allowed to
      covertly recycle a limited amount of their previously published material but
      mainly at the phrase level and only when it is composed of very complex
      descriptions laden with technical terms for which there are no suitable
      substitutes. Authors may recycle longer segments of text using standard scholarly
      conventions of quotation and attribution or via some other informal means that
      alerts readers as to the scope of the recycling, thereby ensuring transparency.
      The use of percent similarity scores as thresholds for acceptable amounts of
      reuse should be discouraged. Instead, editors should be given the flexibility to
      evaluate each instance of recycling by taking into account factors such as the
      technical nature of the recycled text and the language proficiency of the
      authors. This article is a response to the following commentary:
      http://researchintegrityjournal.biomedcentral.com/articles/10.1186/s41073-017
      0025-z.

PMID- 29451561
TI  - What incentives increase data sharing in health and medical research? A
      systematic review.
AB  - Background: The foundation of health and medical research is data. Data sharing
      facilitates the progress of research and strengthens science. Data sharing in
      research is widely discussed in the literature; however, there are seemingly no
      evidence-based incentives that promote data sharing. Methods: A systematic review
      (registration: 10.17605/OSF.IO/6PZ5E) of the health and medical research
      literature was used to uncover any evidence-based incentives, with pre- and post
      empirical data that examined data sharing rates. We were also interested in
      quantifying and classifying the number of opinion pieces on the importance of
      incentives, the number observational studies that analysed data sharing rates and
      practices, and strategies aimed at increasing data sharing rates. Results: Only
      one incentive (using open data badges) has been tested in health and medical
      research that examined data sharing rates. The number of opinion pieces (n = 85)
      out-weighed the number of article-testing strategies (n = 76), and the number of
      observational studies exceeded them both (n = 106). Conclusions: Given that data
      is the foundation of evidence-based health and medical research, it is
      paradoxical that there is only one evidence-based incentive to promote data
      sharing. More well-designed studies are needed in order to increase the currently
      low rates of data sharing.

PMID- 29451563
TI  - A Highly Sensitive Non-Radioactive Activity Assay for AMP-Activated Protein
      Kinase (AMPK).
AB  - While many methods exist to quantitatively determine protein kinase activities,
      32P-based radioactive assays remain the workhorse of many laboratories due to
      their high sensitivity, high signal to noise ratio, lack of interference by
      fluorescent and light-absorbing small molecules, and easy quantitation. Here, we
      demonstrate that the interaction between the yeast Rad53 Forkhead-associated
      (FHA) domain and a peptide optimized for phosphorylation by AMP-Activated Protein
      Kinase (AMPK), which has previously been exploited for the generation of
      intracellular phosphorylation sensors, can serve as a readout for a highly
      sensitive two-step AMPK AlphaScreen kinase assay with exceptional signal-to-noise
      ratio.

PMID- 29451564
TI  - Correction to: micronutrient deficiency conditions: Global Health issues.
AB  - [This corrects the article DOI: 10.1007/BF03391600.].

PMID- 29451566
TI  - Rational fabrication of silver-coated AFM TERS tips with a high enhancement and
      long lifetime.
AB  - Tip-enhanced Raman spectroscopy (TERS), known as nanospectroscopy, has received
      increasing interest as it can provide nanometer spatial resolution and chemical
      fingerprint information of samples simultaneously. Since Ag tips are well
      accepted to show a higher TERS enhancement than that of gold tips, there is an
      urgent quest for Ag TERS tips with a high enhancement, long lifetime, and high
      reproducibility, especially for atomic force microscopy (AFM)-based TERS. Herein,
      we developed an electrodeposition method to fabricate Ag-coated AFM TERS tips in
      a highly controllable and reproducible way. We investigated the influence of the
      electrodeposition potential and time on the morphology and radius of the tip. The
      radii of Ag-coated AFM tips can be rationally controlled at a few to hundreds
      nanometers, which allows us to systematically study the dependence of the TERS
      enhancement on the tip radius. The Ag-coated AFM tips show the highest TERS
      enhancement under 632.8 nm laser excitation and a broad localized surface plasmon
      resonance (LSPR) response when coupled to a Au substrate. The tips exhibit a
      lifetime of 13 days, which is particularly important for applications that need a
      long measuring time.

PMID- 29451565
TI  - Reporting of sex and gender in randomized controlled trials in Canada: a cross
      sectional methods study.
AB  - Background: Accurate reporting on sex and gender in health research is integral
      to ensuring that health interventions are safe and effective. In Canada and
      internationally, governments, research organizations, journal editors, and health
      agencies have called for more inclusive research, provision of sex-disaggregated
      data, and the integration of sex and gender analysis throughout the research
      process. Sex and gender analysis is generally defined as an approach for
      considering how and why different subpopulations (e.g., of diverse genders, ages,
      and social locations) may experience health conditions and interventions in
      different or similar ways.The objective of this study was to assess the extent
      and nature of reporting about sex and/or gender, including whether sex and gender
      analysis (SGA) was carried out in a sample of Canadian randomized controlled
      trials (RCTs) with human participants. Methods: We searched MEDLINE from 01
      January 2013 to 23 July 2014 using a validated filter for identification of RCTs,
      combined with terms related to Canada. Two reviewers screened the search results
      to identify the first 100 RCTs that were either identified in the trial
      publication as funded by a Canadian organization or which had a first or last
      author based in Canada. Data were independently extracted by two people from 10%
      of the RCTs during an initial training period; once agreement was reached on this
      sample, the remainder of the data extraction was completed by one person and
      verified by a second. Results: The search yielded 1433 records. We screened 256
      records to identify 100 RCTs which met our eligibility criteria. The median
      sample size of the RCTs was 107 participants (range 12-6085). While 98% of
      studies described the demographic composition of their participants by sex, only
      6% conducted a subgroup analysis across sex and 4% reported sex-disaggregated
      data. No article defined "sex" and/or "gender." No publication carried out a
      comprehensive sex and gender analysis. Conclusions: Findings highlight poor
      uptake of sex and gender considerations in the Canadian RCT context and
      underscore the need for better articulated guidance on sex and gender analysis to
      improve reporting of evidence, inform policy development, and guide future
      research.

PMID- 29451567
TI  - Stable, small, specific, low-valency quantum dots for single-molecule imaging.
AB  - We have developed a strategy for synthesizing immediately activable, water
      soluble, compact (~10-12 nm hydrodynamic diameter) quantum dots with a small
      number of stable and controllable conjugation handles for long distance delivery
      and subsequent biomolecule conjugation. Upon covalent conjugation with engineered
      monovalent streptavidin, the sample results in a population consisting of low
      valency quantum dots. Alternatively, we have synthesized quantum dots with a
      small number of biotin molecules that can self-assemble with engineered divalent
      streptavidin via high-affinity biotin-streptavidin interactions. Being compact,
      stable and highly specific against biotinylated proteins of interest, these low
      valency quantum dots are ideal for labeling and tracking single molecules on the
      cell surface with high spatiotemporal resolution for different biological systems
      and applications.

PMID- 29451569
TI  - Metal-free NaI/TBHP-mediated sulfonylation of thiols with sulfonyl hydrazides.
AB  - A highly efficient sulfonylation of thiols has been achieved through the metal
      free NaI/TBHP-mediated cross-coupling of sulfonyl hydrazides and thiols at room
      temperature. This method provides a convenient and practical route to
      thiosulfonates in 84-99% yields (39 examples) with wide functional group
      compatibility.

PMID- 29451570
TI  - Insights into the formation mechanism of two-dimensional lead halide
      nanostructures.
AB  - We present a colloidal synthesis strategy for lead halide nanosheets with a
      thickness of far below 100 nm. Due to the layered structure and the synthesis
      parameters the crystals of PbI2 are initially composed of many polytypes. We
      propose a mechanism which gives insight into the chemical process of the PbI2
      formation. Further, we found that the crystal structure changes with increasing
      reaction temperature or by performing the synthesis for longer time periods
      changing for the final 2H structure. In addition, we demonstrate a route to
      prepare nanosheets of lead bromide as well as lead chloride in a similar way.
      Lead halides can be used as a detector material for high-energy photons including
      gamma and X-rays.

PMID- 29451571
TI  - Sea spray aerosol chemical composition: elemental and molecular mimics for
      laboratory studies of heterogeneous and multiphase reactions.
AB  - Sea spray aerosol particles (SSA), formed through wave breaking at the ocean
      surface, contribute to natural aerosol particle concentrations in remote regions
      of Earth's atmosphere, and alter the direct and indirect effects of aerosol
      particles on Earth's radiation budget. In addition, sea spray aerosol serves as
      suspended surface area that can catalyze trace gas reactions. It has been shown
      repeatedly that sea spray aerosol is heavily enriched in organic material
      compared to the surface ocean. The selective enrichment of organic material
      complicates the selection of representative molecular mimics of SSA for
      laboratory or computational studies. In this review, we first provide a short
      introduction to SSA formation processes and discuss chemical transformations of
      SSA that occur in polluted coastal regions and remote pristine air. We then focus
      on existing literature of the chemical composition of nascent SSA generated in
      controlled laboratory experiments and field investigations. We combine the
      evidence on the chemical properties of nascent SSA with literature measurements
      of SSA water uptake to assess SSA molecular composition and liquid water content.
      Efforts to speciate SSA organic material into molecular classes and specific
      molecules have led to the identification of saccharides, alkanes, free fatty
      acids, anionic surfactants, dicarboxylic acids, amino acids, proteinaceous
      matter, and other large macromolecules. However to date, less than 25% of the
      organic mass of nascent SSA has been quantified at a molecular level. As
      discussed here, quantitative measurements of size resolved elemental ratios,
      combined with determinations of water uptake properties, provides unique insight
      on the concentration of ions within SSA as a function of particle size, pointing
      to a controlling role for relative humidity and the hygroscopicity of SSA organic
      material at small particle diameters.

PMID- 29451572
TI  - 3D printed scaffolds with gradient porosity based on a cellulose nanocrystal
      hydrogel.
AB  - 3-Dimensional (3D) printing provides a unique methodology for the customization
      of biomedical scaffolds with respect to size, shape, pore structure and pore
      orientation useful for tissue repair and regeneration. 3D printing was used to
      fabricate fully bio-based porous scaffolds of a double crosslinked
      interpenetrating polymer network (IPN) from a hydrogel ink of sodium alginate and
      gelatin (SA/G) reinforced with cellulose nanocrystals (CNCs). CNCs provided
      favorable rheological properties required for 3D printing. The 3D printed
      scaffolds were crosslinked sequentially via covalent and ionic reactions
      resulting in dimensionally stable hydrogel scaffolds with pore sizes of 80-2125
      MUm and nanoscaled pore wall roughness (visible from scanning electron
      microscopy) favorable for cell interaction. The 2D wide angle X-ray scattering
      studies showed that the nanocrystals orient preferably in the printing direction;
      the degree of orientation varied between 61-76%. The 3D printing pathways were
      optimised successfully to achieve 3-dimensional scaffolds (Z axis up to 20 mm)
      with uniform as well as gradient pore structures. This study demonstrates the
      potential of 3D printing in developing bio-based scaffolds with controlled pore
      sizes, gradient pore structures and alignment of nanocrystals for optimal tissue
      regeneration.

PMID- 29451568
TI  - Upconversion in photodynamic therapy: plumbing the depths.
AB  - Photodynamic therapy (PDT) involves the combination of non-toxic dyes called
      photosensitizers (PS) and harmless visible light that interact with ambient
      oxygen to give reactive oxygen species (ROS) that can damage biomolecules and
      kill cells. PDT has mostly been developed as a cancer therapy but can also be
      used as an antimicrobial approach against localized infections. However even the
      longest wavelength used for exciting PS (in the 700 nm region) has relatively
      poor tissue penetration, and many PS are much better excited by blue and green
      light. Therefore upconversion nanoparticles (UCNPs) have been investigated in
      order to allow deeper-penetrating near-infrared light (980 nm or 810 nm) to be
      used for PDT. NaYF4 nanoparticles doped with Yb3+ and Er3+ or with Tm3+ and Er3+
      have been attached to PS either by covalent conjugation, or by absorption to the
      coating or shell (used to render the UCNPs biocompatible). Forster resonance
      energy transfer to the PS then allows NIR light energy to be transduced into ROS
      leading to cell killing and tumor regression. Some studies have experimentally
      demonstrated the deep tissue advantage of UCNP-PDT. Recent advances have included
      dye-sensitized UCNPs and UCNPs coupled to PS, and other potentially synergistic
      drug molecules or techniques. A variety of bioimaging modalities have also been
      combined with upconversion PDT. Further studies are necessary to optimize the
      drug-delivery abilities of the UCNPs, improve the quantum yields, allow
      intravenous injection and tumor targeting, and ensure lack of toxicity at the
      required doses before potential clinical applications.

PMID- 29451573
TI  - Wavelength-tunable mid-infrared thermal emitters with a non-volatile phase
      changing material.
AB  - The ability to continuously tune the emission wavelength of mid-infrared thermal
      emitters while maintaining high peak emissivity remains a challenge. By
      incorporating the nonvolatile phase changing material Ge2Sb2Te5 (GST), two
      different kinds of wavelength-tunable mid-infrared thermal emitters based on
      simple layered structures (GST-Al bilayer and Cr-GST-Au trilayer) are
      demonstrated. Aiming at high peak emissivity at a tunable wavelength, an Al film
      and an ultrathin (~5 nm) top Cr film are adopted for these two structures,
      respectively. The gradual phase transition of GST provides a tunable peak
      wavelength between 7 MUm and 13 MUm while high peak emissivity (>0.75 and >0.63
      for the GST-Al and Cr-GST-Au emitters, respectively) is maintained. This study
      shows the capability of controlling the thermal emission wavelength, the
      application of which may be extended to gas sensors, infrared imaging, solar
      thermophotovoltaics, and radiative coolers.

PMID- 29451574
TI  - Diastereoselective synthesis, structure and reactivity studies of
      ferrocenyloxazoline gold(i) and gold(ii) complexes.
AB  - In the last few decades, gold complexes have demonstrated huge potential for soft
      Lewis acid catalysis. Despite the intensive research on Au complexes and planar
      chiral metallacycles, enantiopure ferrocenylgold complexes have - surprisingly -
      not been reported until the studies presented in this article. Herein, we report
      the asymmetric synthesis of planar chiral ferrocenyl Au(i) complexes. These
      dinuclear species form helically chiral ten-membered (NCCCAu)2 rings stabilized
      by aurophilic interactions. In supramolecular solid state structures, linear,
      zigzag or helical Au(i) wires with regular AuAu separations were observed. The
      dissolved dinuclear entities could be oxidized by Au(i) to unique ferrocenyl
      Au(ii) complexes featuring short Au(ii)-Au(ii) bonds, while the ferrocene core
      remained intact. However, our initial studies revealed the issue of
      configurational lability of the ferrocenyl Au(ii) complexes in terms of the
      element of planar chirality in the presence of the gold source, (Me2S)AuCl. This
      was successfully addressed by a systematic study implementing permanent sigma
      donor ortho-protecting groups such as methyl and trimethylsilyl, which impede an
      epimerization event. Oxidation of the dinuclear Au(i) complexes was also
      accomplished by oxidative addition reactions with halogenated solvents,
      preferably CHCl3. Additional reactivity studies revealed that dinuclear Au(ii)
      dihalide complexes are also formed with reactive alkylhalides such as
      iodomethane, benzylbromide and benzyliodide. Interestingly, the whole spectral
      range of colors (violet, blue, green, yellow, and red) is covered by the title
      complexes depending on the Au oxidation state and the anionic ligands in the
      Au(ii) complexes. This appears to be quite unusual for ferrocenes, which
      typically adopt orange to red colors in a non-oxidized state.

PMID- 29451575
TI  - Functionalized Cu3BiS3 nanoparticles for dual-modal imaging and targeted
      photothermal/photodynamic therapy.
AB  - Multifunctional nano-biomaterials with the integration of diagnostic and
      therapeutic functions have shown great promise in improving the efficacy of
      cancer therapy. Herein, a new nanoplatform based on functionalized Cu3BiS3
      nanoparticles (NPs) is fabricated for tumour-targeted combination phototherapy.
      The as-synthesized hydrophobic Cu3BiS3 NPs are modified with DSPE-PEG/DSPE-PEG
      NH2, followed by the conjugation of the photosensitizer chlorin e6 (Ce6) and the
      target ligand folic acid (FA). The introduced Ce6 can further form a chelate
      complex with Gd3+. The rationally designed Cu3BiS3-PEG-(Ce6-Gd3+)-FA NPs, which
      have high physiological stability and good biocompatibility, can specifically
      target FA-receptor over-expressed tumour cells. The Cu3BiS3-PEG-(Ce6-Gd3+)-FA NPs
      exhibit effective dual-modal CT and MR imaging in the xenografted HeLa tumours.
      Importantly, excellent in vivo anti-tumour effects have been achieved by
      synergistic photothermal/photodynamic therapy using the multifunctional NPs. We
      expect that this versatile nanoplatform will play a role in exploring precise
      cancer diagnosis and therapy.

PMID- 29451576
TI  - ortho-Chlorination of phenoxy 1,2-dioxetane yields superior chemiluminescent
      probes for in vitro and in vivo imaging.
AB  - A recent methodology, developed by our group, has enabled a dramatic improvement
      in the emissive nature of the excited species, formed during the chemiexcitation
      of dioxetanes under physiological conditions. This approach has resulted in the
      discovery of distinct phenoxy-dioxetane luminophores that produce a
      chemiluminescence signal via a direct-mode of emission. Here, we show a
      significant pKa effect of our new phenoxy-dioxetanes on their chemiexcitation and
      on their ability to serve as chemiluminescent turn-ON probes for biological
      applications. Using an appropriate phenoxy-dioxetane probe with a direct-mode of
      emission, we were able to image beta-galactosidase activity, in cancer cells and
      in tumor-bearing mice. To the best of our knowledge, this is the first example to
      demonstrate in vitro and in vivo endogenous enzymatic chemiluminescence images
      obtained by a single-component phenoxy-dioxetane probe. We anticipate that our
      strategy, for the design and synthesis of such distinct luminophores, will assist
      in providing new effective turn-ON probes for non-invasive intravital
      chemiluminescence imaging techniques.

PMID- 29451577
TI  - An upconversion nanoplatform with extracellular pH-driven tumor-targeting ability
      for improved photodynamic therapy.
AB  - Upconversion nanoparticles (UCNPs) are widely utilized for photodynamic therapy
      (PDT) due to their specific upconverting luminescence that utilizes near infrared
      (NIR) light to excite photosensitizers (PSs) for PDT. The efficiency of UCNP
      based PDT will be improved if the cancer-targeting property of nanomedicine is
      enhanced. Herein, we employed the pH low insertion peptide (pHLIP), a cancer
      targeting moiety, to functionalize an 808 nm excited UCNP-based nanoplatform that
      has a minimized over-heating effect to perform PDT. pHLIP can bring cargo
      specifically into cancer cells under an acidic environment, realizing the
      effective active-targeting abilities to cancer cells or tumor due to acidosis.
      The pHLIP-functionalized nanoplatform was assembled and well characterized. The
      nanoplatform shows an efficient NIR-irradiated PDT effect in cancer cells,
      especially under a slightly acidic condition that mimics the tumor
      microenvironment, and this effectiveness is attributed to the targeting
      properties of pHLIP to cancer cells under acidic conditions that favor the entry
      of the nanoplatform. Furthermore, the pHLIP-functionalized nanoplatform shows a
      favorable safety profile in mice with a high maximum tolerated dose (MTD), which
      may broaden the availability of administration in vivo. The efficient in vivo
      antitumor activity is achieved through intratumor injection of the nanoplatform
      followed by NIR irradiation on the breast tumor. The nanoparticles are largely
      accumulated in the tumor site, revealing the excellent tumor-targeting properties
      of the pHLIP-functionalized nanoplatform, which ensures efficient PDT in vivo.
      Moreover, the nanoparticles have a long retention time in the bloodstream,
      indicating their stability in vivo. Overall, we provide an example of a UCNP
      based nanosystem with tumor-targeting properties to perform efficient PDT both in
      vitro and in vivo.

PMID- 29451578
TI  - A three-dimensional (time, wavelength and intensity) functioning fluorescent
      probe for the selective recognition/discrimination of Cu2+, Hg2+, Fe3+ and F-
      ions.
AB  - We have strategically incorporated three different fluorophores at tren to
      construct a multi-energy donor/acceptor "smart" probe L. This probe operates by
      using three-dimensional scales (response time, wavelength and fluorescence
      intensity) which allows for the selective recognition and discrimination of the
      Cu2+, Hg2+, Fe3+ and F- ions.

PMID- 29451579
TI  - Self-assembly of singlet-emitting double-helical silver dimers: the curious
      coordination chemistry and fluorescence of bisquinolylpyridone.
AB  - 2,6-Bis(2-quinolyl)-4(1H)-pyridone 1, a novel quinoline analogue of the well
      known ligand 2-terpyridone, shows unusual fluorescence with a large Stokes shift
      and low energy emission. Pyridine-pyridone tautomerism is investigated by NMR and
      theoretical methods and indicates that the low energy emission is from the
      pyridine form. 1 reacts with Ag(i) salts to give a double helical Ag2N6 core
      showing a BLUE shift in fluorescence with respect to the free ligand, which has
      been characterised experimentally and theoretically as involving an unusual mixed
      MLCT/ILCT excited state and emission from a singlet state.

PMID- 29451580
TI  - Covalent organic nanosheets for effective charge transport layers in planar-type
      perovskite solar cells.
AB  - Herein, solvent-treated bandgap-tunable covalent organic nanosheets (CONs) were
      prepared via the Stille cross-coupling reaction. These materials are considered
      useful as interlayers in photovoltaic devices upon the alignment of energy levels
      between other components. Among various types of solar cells, according to the
      organic-interlayer study, inverted planar perovskite solar cells (PSCs) are
      mostly demanded to effectively transport and collect charge carriers due to their
      high performance. At first, the C-V analysis proved the energy levels of the
      frontier orbitals for CON-10 and CON-16 nanosheets; this verified the suitability
      of these nanosheets as hole transport layers (HTLs) with the PEDOT:PSS upon
      casting both films from DMSO. It became evident, however, that the hole transport
      property of the PEDOT:PSS on the CON-16 layer was unfavorable with the increasing
      UPS-proven hole injection barrier. In addition, both CONs induced a rough surface
      morphology; however, CON-10 showed a relatively smooth surface as compared to CON
      16 based on the Scanning electron microscopy (SEM) and Atomic force microscopy
      (AFM) profiles; furthermore, their surface properties influenced both the
      PEDOT:PSS layers and the perovskite layers. Especially, the XRD profiles
      presented an enhanced crystallinity of the perovskite layers with CON-10. All
      these aspects indicate that CON-10 is a more effective HTL material, and several
      versions of perovskite solar cells (PSCs) have been fabricated with/without CON
      10 and CON-16 together with the PEDOT:PSS to determine the more-HTL-suitable CON.
      As a result, the power conversion efficiencies (PCEs) of the optimized devices
      with CON-10 exhibited a value of 10.2%, which represented a 1% increase over
      those of the reference devices without the CONs and was 4% higher than that of
      the CON-16 devices. Moreover, the devices with CON-10 were further optimized with
      TiOx using Al electrodes, leading to a PCE increase of these devices that became
      slightly higher than the PCEs of the device with CON-10 and without TiOx. This
      tendency was supported by photoluminescence (PL) spectroscopy, photocurrent
      density (Jph), and space-charge-limited current (SCLC) mobility results.

PMID- 29451581
TI  - Tautomerism and electronic spectroscopy of protonated 1- and 2-aminonaphthalene.
AB  - Experimental and theoretical investigations of the excited states of protonated 1
      and 2-aminonaphthalene are presented. The electronic spectra are obtained by
      laser induced photofragmentation of the ions captured in a cold ion trap. Using
      ab initio calculations, the electronic spectra can be assigned to different
      tautomers which have the proton on the amino group or on the naphthalene moiety.
      It is shown that the tautomer distribution can be varied by changing the
      electrospray source conditions, favoring either the most stable form in solution
      (amino protonation) or that in the gas phase (aromatic ring protonation).
      Calculations for larger amino-polyaromatics predict that these systems should
      behave as "proton sponges" i.e. have a proton affinity larger than 11 eV.

PMID- 29451582
TI  - Adsorptive removal of organic dyes from aqueous solution by a Zr-based metal
      organic framework: effects of Ce(iii) doping.
AB  - Herein, we report the synthesis and characterization of Ce(iii)-doped UiO-66
      nanocrystals, revealing their potential to efficiently remove organic dyes such
      as methylene blue (MB), methyl orange (MO), Congo red (CR), and acid chrome blue
      K (AC) from aqueous solutions. Specifically, the room-temperature adsorption
      capacities of Ce(iii)-doped UiO-66 equaled 145.3 (MB), 639.6 (MO), and 826.7 (CR)
      mg g-1, exceeding those reported for pristine UiO-66 by 490, 270, and 70%,
      respectively. The above behavior was rationalized based on zeta potential and
      adsorption isotherm investigations, which revealed that Ce(iii) doping increases
      the number of adsorption sites and promotes pi-pi interactions between the
      adsorbent and the adsorbate, thus improving the adsorption capacity for cationic
      and anionic dyes and overriding the effect of electrostatic interactions. The
      obtained results shed light on the mechanism of organic dye adsorption on metal
      organic frameworks, additionally revealing that the synergetic interplay of
      electrostatic, pi-pi, and hydrophobic interactions results in the operation of
      two distinct adsorption regimes depending on adsorbate concentration.

PMID- 29451583
TI  - An asymmetric organocatalytic vinylogous Mannich reaction of 3-methyl-5-arylfuran
      2(3H)-ones with N-(2-pyridinesulfonyl) imines: enantioselective synthesis of
      delta-amino gamma,gamma-disubstituted butenolides.
AB  - An asymmetric organocatalytic vinylogous Mannich reaction of 3-methyl-5-arylfuran
      2(3H)-ones with N-(2-pyridinesulfonyl)imines has been developed with 5 mol%
      thiourea-tertiary amine as the catalyst. A series of delta-amino gamma,gamma
      disubstituted butenolides bearing adjacent quaternary and tertiary stereocenters
      are efficiently obtained with satisfactory results (up to 90% yield, 90 : 10 dr,
      and 95 : 5 er).

PMID- 29451584
TI  - Exposure to violence: associations with psychiatric disorders in Brazilian youth.
AB  - OBJECTIVE: The effects of exposure to violent events in adolescence have not been
      sufficiently studied in middle-income countries such as Brazil. The aims of this
      study are to investigate the prevalence of psychiatric disorders among 12-year
      olds in two neighborhoods with different socioeconomic status (SES) levels in Sao
      Paulo and to examine the influence of previous violent events and SES on the
      prevalence of psychiatric disorders. METHODS: Students from nine public schools
      in two neighborhoods of Sao Paulo were recruited. Students and parents answered
      questions about demographic characteristics, SES, urbanicity and violent
      experiences. All participants completed the Kiddie Schedule for Affective
      Disorders and Schizophrenia (K-SADS) to obtain DSM-IV diagnoses. The data were
      analyzed using weighted logistic regression with neighborhood stratification
      after adjusting for neighborhood characteristics, gender, SES and previous
      traumatic events. RESULTS: The sample included 180 individuals, of whom 61.3%
      were from low SES and 39.3% had experienced a traumatic event. The weighted
      prevalence of psychiatric disorders was 21.7%. Having experienced a traumatic
      event and having low SES were associated with having an internalizing (adjusted
      OR = 5.46; 2.17-13.74) or externalizing disorder (adjusted OR = 4.33; 1.85
      10.15). CONCLUSIONS: Investment in reducing SES inequalities and preventing
      violent events during childhood may improve the mental health of youths from low
      SES backgrounds.

PMID- 29451585
TI  - Psychoactive substance abuse and dependence and its association with anxiety
      disorders: a population-based study of young adults in Brazil.
AB  - OBJECTIVE: To evaluate the association between abuse of and dependence on
      different psychoactive substances and the presence of anxiety disorders in a
      sample of young adults from a city in southern Brazil. METHODS: Between 2007 and
      2009, we carried out a cross-sectional, population-based study of individuals
      aged 18-24 years who lived in Pelotas, a city in southern Brazil. We evaluated
      anxiety disorders using the Mini International Neuropsychiatric Interview 5.0
      (MINI), and use of psychoactive substances with the Alcohol, Smoking, and
      Substance Involvement Screening Test (ASSIST 2.0/0MS). We used Fisher's exact
      test for univariate analysis, and Poisson regression models with robust variance
      for multivariable analysis. RESULTS: The sample consisted of 1,560 young adults.
      The overall prevalence of abuse/dependence was 26.9% for alcohol, 24.9% for
      tobacco, and 7.3% for illicit substances. Individuals with agoraphobia had a 32%
      higher prevalence of tobacco abuse/dependence (prevalence ratio [PR] = 1.32
      [95%CI 1.01-1.74]). Individuals with posttraumatic stress disorder (PTSD) or
      generalized anxiety disorder (GAD) had a 2.41-fold (95%CI 1.22-4.77) and 1.76
      fold (95%CI 1.00-3.11) higher prevalence of illicit substance abuse/dependence,
      respectively. CONCLUSION: In this population-based sample, we found associations
      between GAD, PTSD, and increased prevalence of illicit substance
      abuse/dependence. In addition, individuals with agoraphobia seem to have
      increased tobacco abuse/dependence.

PMID- 29451586
TI  - Virtual reality exposure therapy for fear of driving: analysis of clinical
      characteristics, physiological response, and sense of presence.
AB  - OBJECTIVE: To investigate the reactions of women with driving phobia to a
      therapeutic program of scheduled virtual reality exposure treatment (VRET)
      sessions. METHODS: The study intervention consisted of a computer game with car
      driving scenarios that included several traffic situations. We investigated the
      participants' sense of presence, subjective distress, and physiological responses
      during eight virtual-reality exposures. We also evaluated clinical
      characteristics, driving cognitions, and quality of life in the participants.
      RESULTS: Thirteen women were selected. Eight were able to complete the protocol.
      After VRET, there was a decrease in the frequency of distorted thoughts and state
      anxiety scores, as well as a slight improvement in quality of life. Subjective
      discomfort scores, heart rate variation, and sense of presence scores confirmed
      that there was sense of presence in the virtual reality environment. CONCLUSION:
      All patients showed some degree of improvement and demonstrated different levels
      of anxiety in subsequent in vivo driving experiences. Our findings suggest that
      VRET could be used to facilitate in vivo exposure, because it can induce
      presence/immersion and reduce anxiety in patients with specific phobia.
      Furthermore, VRET is not associated with any type of risk.

PMID- 29451587
TI  - Diagnosing dementia in lower educated older persons: validation of a Brazilian
      Portuguese version of the Rowland Universal Dementia Assessment Scale (RUDAS).
AB  - OBJECTIVE: To validate the Rowland Universal Dementia Assessment Scale for use in
      Brazil (RUDAS-BR). METHODS: We first completed an English-Brazilian Portuguese
      translation and back-translation of the RUDAS. A total of 135 subjects over 60
      years of age were included: 65 cognitively healthy and 70 with Alzheimer's
      disease (AD) according to the DSM-IV and Neurological and Communicative Disorders
      and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)
      criteria. All participants completed an interview and were screened for
      depression. The receiver operating characteristic curves of the RUDAS were
      compared with those of the Mini Mental State Examination (MMSE) regarding the
      sensitivity and specificity of cutoffs, taking education into consideration.
      RESULTS: The areas under the curve were similar for the RUDAS-BR (0.87 [95%CI
      0.82-0.93]) and the MMSE (0.84 [95%CI 0.7-0.90]). RUDAS-BR scores < 23 indicated
      dementia, with sensitivity of 81.5% and specificity of 76.1%. MMSE < 24 indicated
      dementia, with sensitivity of 72.3% and specificity of 78.9%. The cutoff score
      was influenced by years of education on the MMSE, but not on the RUDAS-BR.
      CONCLUSIONS: The RUDAS-BR is as accurate as the MMSE in screening for dementia.
      RUDAS-BR scores were not influenced by education. The RUDAS-BR may improve the
      cognitive assessment of older persons who are illiterate or of lower educational
      attainment.

PMID- 29451588
TI  - Religiosity, depression, and quality of life in bipolar disorder: a two-year
      prospective study.
AB  - OBJECTIVE: Few quantitative studies have examined the effect of religious
      involvement on the course of bipolar disorder (BD). We investigated the effects
      of religious activity and coping behaviors on the course of depression, mania,
      and quality of life (QoL) in patients with BD. METHODS: Two-year longitudinal
      study of 168 outpatients with BD. Linear regression was used to examine
      associations between religious predictors and outcome variables (manic symptoms,
      depression, QoL), controlling for sociodemographic variables. RESULTS: Among the
      158 patients reassessed after 2 years, positive religious coping at T1 predicted
      better QoL across all four domains: physical (beta = 10.2, 95%CI 4.2 to 16.1),
      mental (beta = 13.4, 95%CI 7.1 to 19.7), social (beta = 10.5, 95%CI 3.6 to
      17.33), and environmental (beta = 11.1, 95%CI 6.2 to 16.1) at T2. Negative
      religious coping at T1 predicted worse mental (beta = -28.1, 95%CI -52.06 to 
      4.2) and environmental (beta = -20.4, 95%CI -39.3 to -1.6) QoL. Intrinsic
      religiosity at T1 predicted better environmental QoL (beta = 9.56, 95%CI 2.76 to
      16.36) at T2. Negative religious coping at T1 predicted manic symptoms (beta =
      4.1) at T2. CONCLUSION: Religiosity/spirituality (R/S) may influence the QoL of
      patients with BD over time, even among euthymic patients. Targeting R/S
      (especially positive and negative religious coping) in psychosocial interventions
      may enhance the quality of recovery in patients with BD.

PMID- 29451589
TI  - Active Brazilian crack cocaine users: nutritional, anthropometric, and drug use
      profiles.
AB  - OBJECTIVE: To evaluate the nutritional status of crack users and to analyze its
      correlation with drug use profiles. METHODS: Cross-sectional study with 108 crack
      users. Anthropometric data were assessed through body mass index (BMI) and
      bioimpedance (BIA) measurements. A blood test to analyze hematocrit, hemoglobin,
      glucose, and lipid profiles was also performed. Crack use was determined through
      a standardized interview. RESULTS: Based on BMI and BIA, most individuals were
      eutrophic (about 70%). Regarding hematological parameters, we found that
      hemoglobin and hematocrit levels were below normal for 32.4 and 30.6% of
      patients, respectively. Considering normal parameters, a large part of the sample
      (60.2%) had low levels of HDL cholesterol and high levels of triglycerides (38%).
      There were no significant correlations between drug profile and nutritional
      variables. CONCLUSION: This is a pioneering study that examines the nutritional
      status of crack users. Our results showed that most crack users present normal
      anthropometric findings and the prevalence of underweight is low. However, blood
      analysis showed changes and a specific type of malnutrition.

PMID- 29451590
TI  - By the book: ADHD prevalence in medical students varies with analogous methods of
      addressing DSM items.
AB  - OBJECTIVE: The marked increase in the prevalence of attention
      deficit/hyperactivity disorder (ADHD) among university students gives rise to
      questions about how best to diagnose in this setting. The aim of the present
      study was to calculate ADHD prevalence in a large non-clinical sample of medical
      students using a stepwise design and to determine whether ADHD diagnosis varies
      if interviewees use additional probing procedures to obtain examples of positive
      DSM items. METHODS: A total of 726 students were screened with the Adult Self
      Report Scale (ASRS) and invited for an interview with the Kiddie Schedule for
      Affective Disorders and Schizophrenia (K-SADS) adapted for adults. RESULTS: The
      ASRS was positive for 247 students (37%), although only 83 (7.9%) received an
      ADHD diagnosis. ASRS sensitivity and specificity rates were 0.97 and 0.40,
      respectively. Probing procedures were used with a subgroup of 226 students, which
      decreased the number of ADHD diagnoses to 12 (4.5%). CONCLUSION: Probing for an
      individual's real-life examples during the K-SADS interview almost halved ADHD
      prevalence rate based on the ASRS and K-SADS, which rendered the rate consistent
      with that typically reported for young adults. In reclassified cases, although
      examples of inattention did not match the corresponding DSM item, they often
      referred to another DSM inattention item.

PMID- 29451591
TI  - Impact of aggressive periodontitis and chronic periodontitis on oral health
      related quality of life.
AB  - The purpose of this cross-sectional study was to investigate the effect of
      different forms of periodontal diseases on Oral Health-Related Quality of Life
      (OHRQoL). Fifty-two patients with Aggressive Periodontitis (AP) or Chronic
      Periodontitis (CP) were included: nine patients with Localized Aggressive
      Periodontitis (LAP), thirty-three patients with Generalized Aggressive
      Periodontitis (GAP) and ten patients with Generalized Chronic Periodontitis
      (GCP). Oral Health Impact Profile questionnaires (OHIP-14) were distributed after
      a clinical examination that measured the following periodontal parameters: tooth
      loss, bleeding on probing (BoP), probing depth (PD), gingival recession (REC) and
      clinical attachment level (CAL). The global OHIP-14 score means were 10.6 for
      LAP, 16.5 for GAP, and 17.5 for GCP. A statistically significant difference (p <
      0.01) was observed between the LAP group and the other two groups. There was
      significantly less bleeding and recession in the LAP group than in the patients
      with the generalized forms of periodontitis. LAP, GAP and GCP have an impact on
      patient quality of life when measured using the OHIP-14. Patients with GAP and
      GCP had poorer OHRQoL than LAP patients.

PMID- 29451592
TI  - Prevalence of Streptococcus agalactiae colonization in pregnant women from the
      18th Health Region of Parana State.
AB  - Introduction The aim of this study was to determine the prevalence of GBS
      colonization in pregnant women in a public health service. Methods A study of 496
      pregnant women at 35-37 gestational weeks was conducted from September 2011 to
      March 2014 in 21 municipalities of the 18th Health Region of Parana State.
      Vaginal and anorectal samples of each woman were plated on sheep blood agar, and
      in HPTH and Todd-Hewitt enrichment broths. Results Of the 496 pregnant women, 141
      (28.4%) were positive for GBS based on the combination of the three culture media
      with vaginal and anorectal samples. The prevalence was 23.7% for vaginal samples
      and 21.9% for anorectal ones. Among the variables analyzed in this study, only
      urinary infection was a significant factor (0.026) associated with GBS
      colonization in women. Conclusions Based on these results, health units should
      performs universal screening of pregnant women and hospitals should provide
      adequate prophylaxis, when indicated.

PMID- 29451593
TI  - Preliminary report of body lice infesting homeless people in Brazil.

PMID- 29451594
TI  - Nontuberculous mycobacteria in milk from positive cows in the intradermal
      comparative cervical tuberculin test: implications for human tuberculosis
      infections.
AB  - Although the tuberculin test represents the main in vivo diagnostic method used
      in the control and eradication of bovine tuberculosis, few studies have focused
      on the identification of mycobacteria in the milk from cows positive to the
      tuberculin test. The aim of this study was to identify Mycobacterium species in
      milk samples from cows positive to the comparative intradermal test. Milk samples
      from 142 cows positive to the comparative intradermal test carried out in 4,766
      animals were aseptically collected, cultivated on Lowenstein-Jensen and
      Stonebrink media and incubated for up to 90 days. Colonies compatible with
      mycobacteria were stained by Ziehl-Neelsen to detect acid-fast bacilli, while to
      confirm the Mycobacterium genus, conventional PCR was performed. Fourteen
      mycobacterial strains were isolated from 12 cows (8.4%). The hsp65 gene
      sequencing identified M. engbaekii (n=5), M. arupense (n=4), M. nonchromogenicum
      (n=3), and M. heraklionense (n=2) species belong to the Mycobacterium terrae
      complex. Despite the absence of M. tuberculosis complex species in the milk
      samples, identification of these mycobacteria highlights the risk of pathogen
      transmission from bovines to humans throughout milk or dairy products, since many
      of mycobacterial species described here have been reported in pulmonary and
      extrapulmonary diseases both in immunocompetent and immunocompromised people.

PMID- 29451595
TI  - Evaluation of molluscicidal activity of three mangrove species (Avicennia
      schaueriana, Laguncularia racemosa and Rhizophora mangle) and their effects on
      the bioactivity of Biomphalaria glabrata Say, 1818.
AB  - Schistosomiasis is a disease of global extent reaching populations in social
      vulnerability. One of the control measures of this parasitosis is the use of
      molluscicidal substances that can fight snails of the genus Biomphalaria,
      intermediate hosts of Schistosoma mansoni. The aim of this work was to study the
      toxic activity of three mangrove species (Avicennia schaueriana Stapf. & Leech,
      ex Moldenke, 1939, Laguncularia racemosa (L.) CF Gaertn, 1807 and Rhizophora
      mangle L. 1753) on the biological activities of snails Biomphalaria glabrata.
      Hydroalcoholic extracts were prepared from the stem and leaves of each of the
      three plant species to which mollusks were exposed. The phytochemical analysis of
      plants showed the presence of important metabolites in the leaves and stems of L.
      racemosa and R. mangle, such as tannins and saponins, but the absence of these
      metabolites in A. schaueriana. Leaf and stem extracts of the three plant species
      showed low molluscicidal activity, not reaching the standards determined by the
      World Health Organization (WHO, 1983). L. racemosa and R. mangle has interfered
      with motility, feeding and oviposition of snails, unlike the extracts of A.
      schaueriana, which had no effect on these activities.

PMID- 29451596
TI  - Histopathological characteristics of cutaneous lesions caused by Leishmania
      Viannia panamensis in Panama.
AB  - Cutaneous leishmaniasis (CL) is an endemic disease in the Republic of Panama,
      caused by Leishmania (Viannia) parasites, whose most common clinical
      manifestation is the presence of ulcerated lesions on the skin. These lesions
      usually present a chronic inflammatory reaction, sometimes granulomatous, with
      the presence of lymphocytes, plasma cells and macrophages. This study describes
      the histopathological characteristics found in the skin lesions of patients with
      CL caused by Leishmania (V.) panamensis in Panama. We analyzed 49 skin biopsy
      samples from patients with clinical suspicion of CL, by molecular tests (PCR for
      subgenus Viannia and HSP-70) and by Hematoxylin-Eosin staining. Samples were
      characterized at the species level by PCR-HSP-70/RFLP. From the 49 samples
      studied, 46 (94%) were positive by PCR and were characterized as Leishmania (V.)
      panamensis. Of these, 48% were positive by Hematoxylin-Eosin staining with
      alterations being observed both, in the epidermis (85%) and in the dermis (100%)
      of skin biopsies. The inflammatory infiltrate was characterized according to
      histopathological patterns: lymphohistiocytic (50%), lymphoplasmacytic (61%) and
      granulomatous (46%) infiltration, being the combination of these patterns
      frequently found. The predominant histopathological characteristics observed in
      CL lesions caused by L. (V.) panamensis in Panama were: an intense inflammatory
      reaction in the dermis with a combination of lymphohistiocytic, lymphoplasmacytic
      and granulomatous presentation patterns and the presence of ulcers, acanthosis,
      exocytosis and spongiosis in the epidermis.

PMID- 29451597
TI  - Achatina fulica infected by Angiostrongylus cantonensis on beaches, in the west
      zone of Rio de Janeiro, Brazil.
AB  - Angiostrongylus cantonensis is considered the main etiological agent of
      eosinophilic meningitis in humans. At present, this zoonosis is considered an
      emerging disease mainly in the Americas. The aim of this study was to determine
      the prevalence of Achatina fulica infected by Angiostrongylus cantonensis in
      restinga areas along beaches in the west zone of Rio de Janeiro city, Brazil. The
      study areas included the following beaches: Barra da Tijuca, Recreio dos
      Bandeirantes, Reserva, Prainha and Grumari. Ninety specimens of Achatina fulica
      were collected. Positive molluscs were found only in Barra da Tijuca. Infection
      prevalence was 5.5%. The presence of this parasite in the beachfront areas, in
      the west zone of Rio de Janeiro city demonstrates the potential risk of infection
      for visitors and the expansion of this helminth in the State of Rio de Janeiro.

PMID- 29451598
TI  - Performance of cryptococcal antigen lateral flow assay in serum, cerebrospinal
      fluid, whole blood, and urine in HIV-infected patients with culture-proven
      cryptococcal meningitis admitted at a Brazilian referral center.
AB  - Cryptococcal meningitis is the most common cause of opportunistic meningitis in
      HIV-infected patients in Brazil and causes unacceptable high mortality rates. In
      this study, HIV-infected patients with a first episode of culture-proven
      cryptococcal meningitis in cerebrospinal fluid (CSF) were prospectively included
      in order to evaluate sensitivity of cryptococcal antigen (CrAg) lateral flow
      assay (LFA) in serum, CSF, whole blood (fingerstick), and fresh urine. In
      addition, HIV-infected patients with other neurological confirmed diseases were
      included in order to evaluate the specificity of CrAg LFA in serum. Twenty
      patients with cryptococcal meningitis were included and in 19 of them, CrAg LFA
      in CSF, serum, and whole blood were positive (95% sensitivity). In 18 patients,
      India ink test was positive in CSF (90% sensitivity), and in 16 cases, CrAg LFA
      was positive in urine (80% sensitivity). Thirty-six HIV-infected patients with
      other neurological diseases had negative results of CrAg LFA in serum (100%
      specificity). In conclusion, CrAg LFA in serum, CSF, and whole blood showed high
      sensitivity and specificity. Whole blood CrAg LFA seems to be a good and reliable
      strategy to improve AIDS-related cryptococcal meningitis diagnosis in Brazil.

PMID- 29451599
TI  - First case report of atypical disseminated cutaneous leishmaniasis in an opium
      abuser in Iran.
AB  - Leishmaniasis is a worldwide tropical infectious disease caused by different
      species of intracellular protozoa parasites of the genus Leishmania . Herein, we
      report a 78-year-old man with unusual diffuse cutaneous leishmaniasis (DCL) who
      had a history of opium abuse and chronic obstructive pulmonary disease (COPD). He
      had multiple papular, crusted and severely ulcerated lesions extended to his arm
      and chest. Direct smears and skin punch biopsy of the lesions were suggestive of
      leishmaniasis. Parasite DNA was amplified from ulcers, and identified as
      Leishmania major by PCR-RFLP, confirmed by sequencing analyses. The aim of the
      current study was to bring to attention this atypical form of disease in CL
      endemic countries. Thus, this is the first case of DCL in an opium abuser with
      COPD due to L. major in Northeastern Iran indicating that atypical and extensive
      forms of CL (DCL) owing to L. major are increasing in Iran.

PMID- 29451600
TI  - American tegumentary leishmaniasis: diagnostic and treatment challenges in a
      clinical case.
AB  - This clinical case presents a patient with a raised and ulcerative lesion with
      erythematous edges in the mouth, on the lower lip that was unsuccessfully treated
      as herpes labialis. Clinical data and laboratory tests (Montenegro skin test,
      indirect immunofluorescence, direct parasite search and polymerase chain
      reaction) led to the diagnosis of American tegumentary leishmaniasis caused by
      Leishmania (Viannia) sp. Treatment with pentavalent antimonial (Glucantime(r))
      for 120 days was not effective and administration of amphotericin B for 30 days
      resulted in wound healing. Glucantime(r) treatment protocol was longer than the
      recommended by the Brazilian Ministry of Health in the handbook of mucosal
      leishmaniasis. This suggests that amphotericin B should have been administered
      earlier, preventing the psychological and social problems faced by the patient.
      This study reports a rare clinical case of primary mucosal leishmaniasis on the
      lip that had a delayed diagnosis, highlighting the precariousness in the
      management of disease and showing that, despite the importance of leishmaniasis
      in Brazil, it is still neglected by health professionals.

PMID- 29451601
TI  - Cell Division in genus Corynebacterium: protein-protein interaction and molecular
      docking of SepF and FtsZ in the understanding of cytokinesis in pathogenic
      species.
AB  - The genus Corynebacterium includes species of great importance in medical,
      veterinary and biotechnological fields. The genus-specific families (PLfams) from
      PATRIC have been used to observe conserved proteins associated to all species.
      Our results showed a large number of conserved proteins that are associated with
      the cellular division process. Was not observe in our results other proteins like
      FtsA and ZapA that interact with FtsZ. Our findings point that SepF overlaps the
      function of this proteins explored by molecular docking, protein-protein
      interaction and sequence analysis. Transcriptomic analysis showed that these two
      (Sepf and FtsZ) proteins can be expressed in different conditions together. The
      work presents novelties on molecules participating in the cell division event,
      from the interaction of FtsZ and SepF, as new therapeutic targets.

PMID- 29451602
TI  - Synthesis and Cytotoxic Evaluation of 1H-1,2,3-Triazol-1-ylmethyl-2,3
      dihydronaphtho[1,2-b]furan-4,5-diones.
AB  - The 1,2-naphthoquinone compound was previously considered active against solid
      tumors. Moreover, glycosidase inhibitors such as 1,2,3-1H triazoles has been
      pointed out as efficient compounds in anticancer activity studies. Thus, a series
      of eleven 1,2-naphthoquinones tethered in C2 to 1,2,3-1H-triazoles 9a-k were
      designed, synthesized and their cytotoxic activity evaluated using HCT-116 (colon
      adenocarcinoma), MCF-7 (breast adenocarcinoma) and RPE (human nontumor cell line
      from retinal epithelium). The chemical synthesis was performed from C-3
      allylation of lawsone followed by iodocyclization with subsequent nucleophilic
      displacement with sodium azide and, finally, the 1,3-dipolar cycloaddition
      catalyzed by Cu(I) with terminal alkynes led to the formation of 1H-1,2,3-Triazol
      1-ylmethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-diones in good yields. Compounds
      containing aromatic group linked to 1,2,3-triazole ring (9c, 9d, 9e, 9i)
      presented superior cytotoxic activity against cancer cell lines with IC50 in the
      range of 0.74 to 4.4 uM indicating that the presence of aromatic rings
      substituents in the 1,2,3-1H-triazole moiety is probably responsible for the
      improved cytotoxic activity.

PMID- 29451603
TI  - From Medicinal Chemistry to Human Health: Current Approaches to Drug Discovery
      for Cancer and Neglected Tropical Diseases.
AB  - Scientific and technological breakthroughs have compelled the current players in
      drug discovery to increasingly incorporate knowledge-based approaches. This
      evolving paradigm, which has its roots attached to the recent advances in
      medicinal chemistry, molecular and structural biology, has unprecedentedly
      demanded the development of up-to-date computational approaches, such as bio- and
      chemo-informatics. These tools have been pivotal to catalyzing the ever
      increasing amount of data generated by the molecular sciences, and to converting
      the data into insightful guidelines for use in the research pipeline. As a
      result, ligand- and structure-based drug design have emerged as key pathways to
      address the pharmaceutical industry's striking demands for innovation. These
      approaches depend on a keen integration of experimental and molecular modeling
      methods to surmount the main challenges faced by drug candidates - in vivo
      efficacy, pharmacodynamics, metabolism, pharmacokinetics and safety. To that end,
      the Laboratorio de Quimica Medicinal e Computacional (LQMC) of the Universidade
      de Sao Paulo has developed forefront research on highly prevalent and life
      threatening neglected tropical diseases and cancer. By taking part in global
      initiatives for pharmaceutical innovation, the laboratory has contributed to the
      advance of these critical therapeutic areas through the use of cutting-edge
      strategies in medicinal chemistry.

PMID- 29451604
TI  - Record of predation by two amphibians Rhinella major and Ctenophryne geayi by
      Erythrolamprus dorsocorallinus (Esqueda, Natera, La Marca & Ilija-Fistar, 2005)
      (Serpentes: Dipsadidae) in northwestern Brazil.

PMID- 29451605
TI  - Evaluation of the frequency of Candida spp. in hospitalized and non-hospitalized
      subjects.
AB  - The aim of this study was to evaluate the frequency of Candida species between a
      non-hospitalized and a hospitalized population. For this purpose, samples of
      saliva were sampled through sterile swabs, moistened in peptone water and rubbed
      in the oral cavity of 140 individuals, from which, 70 were hospitalized patients
      from the Medical Clinic of a Teaching Hospital and the other 70 were non
      hospitalized subjects. All saliva samples were plated in Sabouraud Dextrose agar
      added with Chloramphenicol and incubated at 36  degrees C for 48 hours. The
      morphology identification was performed through macroscopic and microscopic
      characterization, the CHROMagar Candida medium and the VITEK(r) system Yeast
      Biochemical Card (bio Merieux SA, France). The results showed a colonization of
      Candida spp. in 85.7% the hospitalized individuals, where the species found were
      C. albicans (60%), C. tropicalis (23.4%), C. krusei (3.3%) and Candida spp.
      (13.3%). In the non-hospitalized individuals the colonization by Candida spp was
      47.1%, and the species found were: C. albicans (45.5%), C.krusei (9.1%), C.
      guilliermondii (9.1% %), C. tropicalis (3.0%), C. famata (3.0%) and Candida spp.
      (30.3%). In spite of their presence in oral cavity in both groups, Candida spp.
      was more frequently isolated in hospitalized individuals, who were 6.73 times
      more likely to have this fungus in the oral cavity and were 3.88 times more
      likely to have Candida albicans.

PMID- 29451606
TI  - Can climate and soil conditions change the morpho-anatomy among individuals from
      different localities? A case study in Aldama grandiflora (Asteraceae).
AB  - Vegetative aerial organs are considerably more exposed to environmental
      conditions and can reflect the specific adaptations of plants to their local
      environment. Aldama grandiflora species are known to be widely distributed in
      Brazil; therefore, individuals from different populations of this species are
      thought to be exposed to different abiotic and biotic conditions. Several
      anatomical studies conducted on Brazilian Aldama species have mainly focused on
      the qualitative anatomical characters or traits of these species, but not on
      their quantitative traits. In this study, we evaluated whether climate and soil
      conditions can change the morphometry among individuals of A. grandiflora
      collected from six sites in the Goias State, Brazil, by assessing their
      anatomical characters. Further, soil sampling was performed, and climate data
      were collected from all the six sites. The analysis indicated few statistical
      differences among the populations evaluated, showing that A. grandiflora
      presented consistent leaf and stem anatomical characteristics. The small morpho
      anatomical differences found among individuals of the different populations
      evaluated, reflected the soil conditions in which these populations were grown.
      Therefore, environmental factors have a significant influence on the morpho
      anatomy of Aldama grandiflora.

PMID- 29451607
TI  - Decolorization of textile industry wastewater in solid state fermentation with
      Peach-Palm (Bactris gasipaes) residue.
AB  - In this work we have assessed the decolorization of textile effluents throughout
      their treatment in a solid-state fermentation (SSF) system. SSF assays were
      conducted with peach-palm (Bactris gasipaes) residue using the white rot fungus
      Ganoderma lucidum EF 31. The influence of the dye concentration and of the
      amounts of peach-palm residue and liquid phase on both the discoloration
      efficiency and enzyme production was studied. According to our results,
      independently of experimental conditions employed, laccase was the main
      ligninolytic enzyme produced by G. lucidum. The highest laccase activity was
      obtained at very low effluent concentrations, suggesting the existence of an
      inhibitory effect of higher concentrations on fungal metabolism. The highest
      percentage of color removal was reached when 10 grams of peach palm residue was
      moistened with 60 mL of the final effluent. In control tests carried out with the
      synthetic dye Remazol Brilliant Blue R (RBBR) decolorization efficiencies about
      20% higher than that achieved with the industrial effluent were achieved. The
      adsorption of RBBR on peach-palm residue was also investigated. Equilibrium tests
      showed that the adsorption of this dye followed both Langmuir and Freundlich
      isotherms. Hence, our experimental results indicate that peach-palm residue is
      suitable substrate for both laccase production and color removal in industrial
      effluents.

PMID- 29451608
TI  - Abiotic factors drives floristic variations of fern's metacommunity in an
      Atlantic Forest remnant.
AB  - We analyzed floristic variations in fern's metacommunity at the local scale and
      their relationship with abiotic factors in an Atlantic Forest remnant of
      northeastern Brazil. Floristic and environmental variations were accessed on ten
      plots of 10 * 20 m. We performed cluster analyses, based on Bray-Curtis
      dissimilarity index to establish the floristic relationship. The influence of
      abiotic factors: luminosity, temperature, relative air humidity and relative soil
      moisture was evaluated from a redundancy analysis. We found 24 species belonging
      to 20 genera and 12 families. The fern's flora showed high floristic
      heterogeneity (>75% for most of the plot's associations). The fern's
      metacommunity was structured along an abiotic gradient modulated by temperature,
      luminosity, and relative soil moisture.

PMID- 29451609
TI  - Diagnostic properties and cutoff points for overweight prediction through
      anthropometric indicators in adolescents from Caracol, Piaui, Brazil, 2011.
AB  - OBJECTIVE: to assess the diagnostic criteria and propose cutoff points for waist
      circumference (WC), arm circumference (AC), leg circumference (LC) and
      waist/height ratio (WHR) for overweight prediction in adolescents. METHODS: a
      census with all individuals aged 13-19 years old (N=1,075) from the municipality
      of Caracol-PI, Brazil was carried out; overweight was defined as body mass index
      (BMI) above one z-score, according to the criterion of the World Health
      Organization. RESULTS: the cutoff points (in centimeters) of WC, AC, LC and WHR
      for overweight prediction were, respectively, 76.4, 26.4, 34.0 and 0.460 in
      males, and 74.6, 27.0, 34.5 and 0.475 in females; the area under the ROC curve
      was above 0.70 (males) and 0.90 (females). CONCLUSION: the anthropometric
      indicators assessed reached satisfactory diagnostic values for overweight
      prediction in adolescents from the Brazilian semi-arid region.

PMID- 29451610
TI  - Coverage, completeness and reliability of the data in the Information System on
      Live Births in public maternity wards in the municipality in Sao Paulo, Brazil,
      2011.
AB  - OBJECTIVE: to assess the coverage, completeness and reliability of data on live
      births in public maternity wards in Sao Paulo, Brazil. METHODS: data recorded in
      the Information System on Live Births (Sinasc) were compared with data collected
      in a field study (gold standard) during three months in 2011 in four maternity
      wards in hospital from the SUS network; kappa coefficient was calculated to
      assess agreement. RESULTS: 5,785 birth records were analyzed; Sinasc coverage was
      99.8% and completeness was 96.2%; kappa values showed excellent and good
      agreement for maternal age (0.99), type of pregnancy, sex and newborn sex and
      birth weight (0.98), type of delivery (0.97), 1 minute (0.96) and 5th (0.95)
      minutes, previous live births (0.87) and education level (0.62); regular
      agreement for prenatal care visits (0.60) and gestational age (0.56); and weak
      agreement for previous stillbirths (0.09). CONCLUSION: in the assessed hospitals,
      Sinasc presented high coverage, completeness and reliability.

PMID- 29451611
TI  - Factors associated with HIV co-infection in cases of acquired syphilis reported
      in a Reference Center for Sexually Transmitted Diseases and AIDS in the
      municipality of Sao Paulo, Brazil, 2014.
AB  - OBJECTIVE: to describe sociodemographic and behavioral characteristics and to
      identify factors associated with human immunodeficiency virus (HIV) co-infection
      in cases of acquired syphilis reported in a Reference Center for Sexually
      Transmitted Diseases (STD) and AIDS. METHODS: cross-sectional study with
      secondary data from a Reference Center for STD and AIDS in the municipality of
      Sao Paulo, Brazil, in 2014; the Poisson regression was used to estimate
      prevalence ratios (PR) and 95% confidence intervals (95%CI). RESULTS: 648 cases
      of acquired syphilis were reported, and 98% were male; 88% were men who have sex
      with men (MSM) and 57% had HIV co-infection; male sex (PR=1.95; 95%CI 1.05;3.61)
      and MSM (PR=1.87; 95%CI 1.38;2.53) were factors independently associated with HIV
      co-infection. CONCLUSION: there was a high prevalence of HIV co-infection in the
      service analyzed, disproportionately affecting MSM who were notified with
      acquired syphilis.

PMID- 29451612
TI  - The challenges to eliminating tuberculosis in Brazil.

PMID- 29451613
TI  - Filling process of the Child Health Record in health care services of Belo
      Horizonte, Minas Gerais, Brazil.
AB  - OBJECTIVE: to describe the filling process of the Child Health Record (CHR) in
      health care services. METHODS: descriptive study held in Belo Horizonte, Minas
      Gerais, Brazil; an interview was conducted with parents/guardians of children
      aged 3-5 years old; 21 essential items to child monitoring were observed in the
      CHR during the 2014 Multi-vaccination Day; fields that should be filled in
      maternity wards, Primary Health Care (PHC), and other services were assessed
      separately. RESULTS: 367 children (96.1%) were included; 44.5% of CHR presented
      >=60% of completeness; among the items that should be recorded in maternity
      wards, birth weight showed the highest proportion of completeness (64.5%); for
      those that should be filled in PHC/other services, records of vaccines (94.0%)
      presented the highest completeness; there was more filling in maternity wards
      than in PHC and other services (p<0.001). CONCLUSION: a low proportion of filling
      was observed, especially in PHC and other services.

PMID- 29451614
TI  - Agreement between underlying cause and preventability of infant deaths before and
      after the investigation in Recife, Pernambuco State, Brazil, 2014.
AB  - OBJECTIVE: to assess the agreement and describe the causes and preventability of
      infant deaths before and after the investigation. METHODS: investigation files
      and death certificates of infants under one year, of mothers living in Recife,
      Brazil, in 2014 were used; the Cohen kappa index was adopted for agreement
      analysis of the underlying causes of death; the list of preventable causes of
      deaths by interventions of the Brazilian National Health System was also adopted.
      RESULTS: 183 infant deaths were analyzed, of which 117 (63.9%) had the underlying
      cause revised; before the investigation, 170 (92.2%) deaths were considered
      preventable, and after investigation, 178 (97.3%); there was reasonable agreement
      (0.338) regarding the underlying causes of death, and moderate (0.439) for
      preventability. CONCLUSION: infant mortality surveillance enabled the improvement
      of vital events information, contributing to the progress in the specification of
      underlying causes of death and in the preventability of infant death.

PMID- 29451615
TI  - Entomological and epidemiological aspects of dengue epidemics in Fortaleza,
      Ceara, Brazil, 2001-2012.
AB  - OBJECTIVE: to characterize the entomological and epidemiological aspects of
      dengue epidemics occurred in Fortaleza, Ceara, Brazil, from 2001 to 2012.
      METHODS: descriptive study with data from the Information System for Notifiable
      Diseases (Sinan), Information System of Hospitalizations due to Yellow Fever and
      Dengue (2001-2009), National Program for Dengue Control (2010-2012), and Rapid
      Survey of Aedes aegypti Infestation Index, referring to the years in which the
      incidence of dengue was above 75%. RESULTS: from 2001 to 2012, 194,446 cases of
      suspected dengue were notified; the epidemic years were 2001, 2006, 2008, 2011
      and 2012; there was a progressive increase in the incidence of the disease
      (587.0/100 thousand inhabitants in 2001 and 1,561.1/100 inhabitants in 2012);
      there was co-circulation of up to three serotypes and high vector infestation,
      especially in water tanks. CONCLUSION: after a long period of virus circulation
      in Fortaleza, dengue remains as an important health issue, with severe cases and
      high fatality rate.

PMID- 29451616
TI  - Counseling by health professionals and healthy behaviors among the elderly:
      population-based study in Pelotas, South of Brazil, 2014.
AB  - OBJECTIVE: to analyze the association between counseling by health care
      professionals and healthy behaviors among the elderly. METHODS: population-based,
      cross-sectional study with elderly individuals (>=60 years) interviewed in 2014;
      Poisson regression was used to estimate crude and adjusted prevalence ratios (PR)
      of associations between counseling by health professionals on the reduction of
      salt, sugar and fat and on the practice of physical activity during the year
      previous to the interview and healthy behaviors. RESULTS: 1,281 elderly
      individuals were interviewed; after adjustments, the elderly who mentioned
      receiving counseling by health professionals reported reduction in the intake of
      salt (PR 1.64; 95%CI 1.41;1.91), sugar and sweets (PR 1.21; 95%CI 1.08;1.36) and
      greater practice of physical activity (PR 1.21; 95%CI 1.06;1.39), when compared
      to the elderly who had not received any counseling. CONCLUSION: the counseling
      carried out by health professionals seems to favor the practice of healthy habits
      among elderly individuals.

PMID- 29451617
TI  - Trends in social security benefits for oral and oropharyngeal cancer from 2006 to
      2013 in Brazil.
AB  - OBJECTIVE: to analyze the trends in the concession of social security sick pay
      for oral and oropharyngeal cancer, from 2006 to 2013, in Brazil. METHODS: time
      series study using data of workers insured by the Brazilian National Institute of
      Social Security (INSS); Prais-Winsten generalized linear regressions were used to
      calculate the annual percentage change (APC). RESULTS: social security benefits
      for oral and oropharyngeal cancer presented significant increase (APC=9.0%; 95%CI
      1.4; 17.4); benefits for other parts of the mouth, nasopharynx, oropharynx, floor
      of mouth and palate have also shown significant increase; the areas of trade
      (5.5%) and manufacturing (5.2%) were the most prevalent activities; there was a
      high proportion of fields in blank in the information systems (average of 72.9%).
      CONCLUSION: trends in occupational benefits for oral and oropharyngeal cancer
      showed significant increase.

PMID- 29451618
TI  - The Association of Vitamin D Levels and the Frailty Phenotype Among Non-geriatric
      Dialysis Patients: A Cross-sectional Study.
AB  - OBJECTIVES: The aim of this study was to investigate the frequency of frailty and
      the association of vitamin D levels and the frailty phenotype among non-geriatric
      dialysis patients. METHOD: Seventy-four stable, chronic hemodialysis patients
      from the hemodialysis unit of the hospital were enrolled in the study. The
      patients' medical histories and laboratory findings were obtained from the
      medical records of the dialysis unit. Serum parathyroid hormone and 25-hydroxy
      vitamin D levels were determined using chemiluminometric immunoassays. Frailty
      was defined by Fried et al. as a phenotype; shrinking, weakness, self-reported
      exhaustion, decreased activity and slowed walking speed were evaluated. RESULTS:
      Forty-one (55%) of the patients were males. The patients were divided into 3
      groups according to frailty scores: 39 (53%) patients were frail, 6 (8%) patients
      were intermediately frail, and 28 (39%) patients were normal. Significant
      differences were found for 25-hydroxy vitamin D and hemoglobin levels among the
      groups; however, no differences were observed in body mass index, comorbidities,
      sex, marital status, education, disease and dialysis durations, or parathyroid
      hormone, creatinine, serum calcium, phosphorus, and potassium levels.
      CONCLUSIONS: Weakness and slowness are serious outcomes of both vitamin D
      deficiency and frailty, and vitamin D deficiency has been associated with
      increased risks of decreased physical activity, falls, fractures and death in
      postmenopausal women and older men. Although studies on frailty have focused on
      older adults, growing evidence indicates that the frailty phenotype is becoming a
      factor associated with poor health outcomes in non-geriatric populations with
      chronic disease.

PMID- 29451619
TI  - Increase of 10% in the Rate of Adverse Drug Reactions for Each Drug Administered
      in Hospitalized Patients.
AB  - OBJECTIVE: To assess the risk factors, incidence and severity of adverse drug
      reactions in in-patients. METHODS: This prospective study evaluated 472 patients
      treated at a teaching hospital in Brazil between 2010 and 2013 by five medical
      specialties: Internal Medicine, General Surgery, Geriatrics, Neurology, and
      Clinical Immunology and Allergy. The following variables were assessed: patient
      age, gender, comorbidities, family history of hypersensitivity, personal and
      family history of atopy, number of prescribed drugs before and during
      hospitalization, hospital diagnoses, days of hospitalization. The patients were
      visited every other day, and medical records were reviewed by the investigators
      to detect adverse drug reactions. RESULTS: There were a total of 94 adverse drug
      reactions in 75 patients. Most reactions were predictable and of moderate
      severity. The incidence of adverse drug reactions was 16.2%, and the incidence
      varied, according to the medical specialty; it was higher in Internal Medicine
      (30%). Antibiotics were the most commonly involved medication. Chronic renal
      failure, longer hospital stay, greater number of diagnoses and greater number of
      medications upon admission were risk factors. For each medication introduced
      during hospitalization, there was a 10% increase in the rate of adverse drug
      reaction. In the present study, the probability of observing an adverse drug
      reaction was 1 in 104 patients per day. CONCLUSIONS: Adverse drug reactions are
      frequent and potentially serious and should be better monitored in patients with
      chronic renal failure or prolonged hospitalization and especially in those on
      'polypharmacy' regimens. The rational use of medications plays an important role
      in preventing adverse drug reactions.

PMID- 29451620
TI  - Application of a pharmacokinetics-pharmacodynamics approach to the free propofol
      plasma levels during coronary artery bypass grafting surgery with hypothermic
      cardiopulmonary bypass.
AB  - OBJECTIVES: The objective of this study was to apply a pharmacokinetics
      pharmacodynamics approach to investigate the free propofol plasma levels in
      patients undergoing coronary artery bypass grafting under hypothermic conditions
      compared with the off-pump procedure. METHODS: Nineteen patients scheduled for on
      pump coronary artery bypass grafting under hypothermic conditions (n=10) or the
      equivalent off-pump surgery (n=9) were anesthetized with sufentanil and propofol
      target-controlled infusion (2 MUg/mL) during surgery. The propofol concentration
      was then reduced to 1 MUg/mL, and a pharmacokinetics-pharmacodynamics analysis
      using the maximum-effect-sigmoid model obtained by plotting the bispectral index
      values against the free propofol plasma levels was performed. RESULTS:
      Significant increases (two- to five-fold) in the free propofol plasma levels were
      observed in the patients subjected to coronary artery bypass grafting under
      hypothermic conditions. The pharmacokinetics of propofol varied according to the
      free drug levels in the hypothermic on-pump group versus the off-pump group.
      After hypothermic coronary artery bypass was initiated, the distribution volume
      increased, and the distribution half-life was prolonged. Propofol target
      controlled infusion was discontinued when orotracheal extubation was indicated,
      and the time to patient extubation was significantly higher in the hypothermic on
      pump group than in the off-pump group (459 versus 273 min, p=0.0048).
      CONCLUSIONS: The orotracheal intubation time was significantly longer in the
      hypothermic on-pump group than in the off-pump group. Additionally, residual
      hypnosis was identified through the pharmacokinetics-pharmacodynamics approach
      based on decreases in drug plasma protein binding in the hypothermic on-pump
      group, which could explain the increased hypnosis observed with this drug in this
      group of patients.

PMID- 29451622
TI  - [Mental health with a gender perspective].

PMID- 29451621
TI  - A comparison of the efficiency of 22G versus 25G needles in EUS-FNA for solid
      pancreatic mass assessment: A systematic review and meta-analysis.
AB  - Our aim in this study was to compare the efficiency of 25G versus 22G needles in
      diagnosing solid pancreatic lesions by EUS-FNA. We performed a systematic review
      and meta-analysis. Studies were identified in five databases using an extensive
      search strategy. Only randomized trials comparing 22G and 25G needles were
      included. The results were analyzed by fixed and random effects. A total of 504
      studies were found in the search, among which 4 randomized studies were selected
      for inclusion in the analysis. A total of 462 patients were evaluated (233: 25G
      needle/229: 22G needle). The diagnostic sensitivity was 93% for the 25G needle
      and 91% for the 22G needle. The specificity of the 25G needle was 87%, and that
      of the 22G needle was 83%. The positive likelihood ratio was 4.57 for the 25G
      needle and 4.26 for the 22G needle. The area under the sROC curve for the 25G
      needle was 0.9705, and it was 0.9795 for the 22G needle, with no statistically
      significant difference between them (p=0.497). Based on randomized studies, this
      meta-analysis did not demonstrate a significant difference between the 22G and
      25G needles used during EUS-FNA in the diagnosis of solid pancreatic lesions.

PMID- 29451623
TI  - [Detection of antibodies against HIV from dry blood samples on filter paper].

PMID- 29451624
TI  - [Morbility in applicants to the career of medicine according to sex].

PMID- 29451625
TI  - [Factors of cardiovascular risk in patients with type 2 diabetes mellitus seen in
      outpatient clinics].

PMID- 29451626
TI  - [Influenza in the State of Mexico: from the pandemic to the endemic].

PMID- 29451627
TI  - [Understanding the factors that determine the perceptive distortion of body image
      in teenagers].

PMID- 29451628
TI  - ?

PMID- 29451629
TI  - [Author's response to Sebastian Garcia Saiso's letter to the editor about the
      article "Implementation of quality indicators of care in public hospitals of the
      third level in Mexico"].

PMID- 29451630
TI  - [Pattern changes in food and beverages expenditure in Mexican households (1984
      2014)].
AB  - OBJECTIVE: To analyze the proportion of expenditure and its frequency in food and
      beverages consumed inside and outside of households, at national and regional
      level, in Mexico between 1984 and 2014. MATERIALS AND METHODS: It analyzes data
      of household expenditure of food and beverages taken from the National Survey of
      Mexican Household Income and Expenditures 1984, 1994, 2005 and 2014. It conducted
      descriptive statistics analyses such as percentages, growth rates and crosstabs.
      RESULTS: There were changes in food expenditure patterns at national and regional
      level. The proportion of expenditure and its frequency increased in non-alcoholic
      beverages, prepared food, meals made outside home and cereals. The proportion of
      expenditure and its frequency decreased in oils and fats, fruits, vegetables,
      sugar and honeys. CONCLUSION: These changes can be related to political,
      economic, social and cultural transformations experienced in the last decades.

PMID- 29451631
TI  - [Effects of SaludArte program in feeding and nutrition components in school
      children in Mexico City].
AB  - OBJECTIVE: To assess the effect of Education in Nutrition and Food Assistance
      components of the SaludArte program in participant schools during 2013-2015.
      MATERIALS AND METHODS: A three cohort comparative study was used, with two type
      of follow-up panel structures: a complete panel and a continuous time, with a
      total of consisting on 1620 scholar children from 144 schools. Information on
      food intake, feeding behaviors, food preservation and hygiene, physical activity
      (PI) and anthropometry was registered. To stablish effect estimates, a difference
      in difference method combined with propensity score matching was carried out; as
      an alternative procedure, logistic-multinomial and logistic regression models
      were also used. RESULTS: Program attributable estimated effects were as follows:
      an increase in personal hygiene (p=0.045), increase in nutrition knowledges
      (p=0.003), PI (p=0.002 2013-2014; p=0.032 2015) and increase in fiber Intake
      (p=0.064). Sugar intake, contrary to the expected showed a significant increase
      (p=0.012 continuous time and; p=0.037 complete time). CONCLUSIONS: SaludArte
      shows positive effects over some components as expected. However in order to
      institutionalize the SaludArte program, it is necessary to consider these learned
      lessons, give it permanence and impulse it in the schools.

PMID- 29451632
TI  - [Oxidative stress, lung function and exposure to air pollutants in Mexican
      schoolchildren with and without asthma].
AB  - OBJECTIVE.: To assess the association between the air pollutants exposure on
      markers of oxidative stress and lung function in schoolchildren with and without
      asthma from Salamanca and Leon Guanajuato, Mexico. MATERIALS AND METHODS: We
      realized determinations of oxidative stress biomarkers and lung function tests in
      314 schoolchildren. Information of air pollutants (O3, SO2, CO, PM2.5 and PM10)
      were obtained from monitoring stations and multiple linear regression models were
      run to assess the association. RESULTS: An increase of 0.09 pmol in conjugated
      dienes was observed by exposure to PM10 lag 1 in asthmatics from Salamanca
      (p<0.05). The exposure to O3 during the same day increased the concentration of
      Lipohydroperoxides in 4.38 nmol in asthmatics of Salamanca, as well as in 2.31
      nmol by exposure to PM10 lag 2 (p<0.05). The forced vital capacity decreased by
      138 and 203 ml in children without asthma, respectively, due to exposure to
      carbon monoxide (p<0.05). CONCLUSIONS: Exposure to air pollutants increase
      oxidative stress and decreased lung function in schoolchildren, with and without
      asthma.

PMID- 29451633
TI  - [Inequity in maternal mortality in Mexico: analyzing inequality on a sub-state
      regional scale].
AB  - OBJECTIVE: To estimate maternal mortality ratios (MMR) for the different sub
      state regions in Mexico in order to identify those with highest maternal
      mortality, as well as the degree of inter-regional inequality. MATERIALS AND
      METHODS: Maternal mortality and registered live births data was taken from
      publicly available official data for the years 2005 to 2014. We regionalized the
      states based on political-administrative divisions within them and calculated MMR
      for these regions, and calculated Gini coefficients. RESULTS: MMR for sub-state
      regions ranges from 16 (Non-Metropolitan Nuevo Leon State) to 160 (Sola de Vega,
      Oaxaca). We identified 13 regions of Very High or Extremely High maternal
      mortality. The national Gini coefficient is 0.175, with the states of Chihuahua,
      Nayarit, Oaxaca and Guerrero standing out for their unequal distribution of
      maternal mortality within their territory. CONCLUSIONS: Even state level averages
      of maternal mortality rates tend to hide important inequalities within states,
      which reflect multiple subjacent inequities.

PMID- 29451634
TI  - [Varicella and herpes zoster: challenges for public health].
AB  - OBJECTIVE: To evaluate the epidemiological behavior of varicella and herpes
      zoster (HZ) to determine the need of health policies to diminish prevalence and
      avoid complications. MATERIALS AND METHODS: To assess frequency, we analyzed data
      from the National Information System for Epidemiological Surveillance (SUIVE)
      from 2000 to 2013; to assess the discharge data of varicella and HZ, we evaluated
      information from the National System of health information (Sinais). RESULTS: The
      average annual cases of chickenpox were 296 733, 57% mostly children under 9
      years, most of them from March to May. From 2004 to 2012 hospital discharge of
      varicella were 17 398, of which 4.6% had meningoecephalitis, 2.5% pneumonia and
      18% other complications. For herpes zoster 7 042 discharges, mostly affected were
      patients 65 years or older, 1.3:1 the woman-man relationship. Main complications
      were: neuralgia (11%), eye involvement (7%), meningoencephalitis (5.4%),
      disseminated disease (2.8%) and others (5.4%); hospital stay was between 6.4 and
      13.3 days. CONCLUSIONS: Data is consistent with that of the literature in other
      countries. The role of vaccination to prevent infection in children and adults is
      discussed.

PMID- 29451635
TI  - [Serum 25-hydroxyvitamin D state in healthy children ten year minors old of
      Barranquilla metropolitan area].
AB  - OBJETIVE: To evaluate the serum 25-hydroxyvitamin D (25-OH-D) levels in healthy
      children under 10 years of the Barranquilla metropolitan area. MATERIALS AND
      METHODS: A descriptive cross-sectional study in which serum levels of 25-OH-D
      were analyzed in 360 healthy children from 2014 to 2015. RESULTS: The median
      value of 25-OH-D serum level was 32.23+/-8.56 ng/mL; 46.38% of children had
      vitamin D levels in the insufficient range (<30 ng/mL), while 3.05% were
      deficient (<20 ng/mL). Soledad and Puerto Colombia were the municipalities with
      more population in this condition. CONCLUSIONS: It is necessary to promote
      vitamin D supplement consumption and healthy lifestyles in order to safely
      improve levels of this micronutrient in the population.

PMID- 29451636
TI  - [Potentially traumatic events and post-traumatic symptomatology in high school
      students].
AB  - OBJECTIVE: Describe the occurrence of potentially traumatic events (PTE) in high
      school students, measure subthreshold post-traumatic symptomatology in those who
      still experience PTE repercussions and associate the symptomatology with
      sociodemographic and PTE characteristics. MATERIALS AND METHODS: Analytic
      transversal study carried out in a convenience sample of one thousand students
      from three high schools in the State of Mexico. The Scale for Post Traumatic
      Stress in University Students was applied. The presence of symptoms, their
      frequency and their association with explanatory variables was assessed by means
      of logistic and quantile logistic regression models, respectively. RESULTS: 80%
      reported PTE. Of this, 79% still experienced current repercussions and almost a
      half presented symptomatology. Gender, number of events, and PTE characteristics
      (perceived and grave symptoms) were associated. CONCLUSIONS: Results suggest to
      intervene early to reduce the risk of developing a disorder.

PMID- 29451637
TI  - Facing death in the clinical practice: a view from nurses in Mexico.
AB  - OBJECTIVE: To explore the views of nurses on death in their practice, and their
      perception about physicians' actions dealing with terminally ill patients.
      MATERIALS AND METHODS: Two hundred ninety-five nurses with experience caring for
      terminally ill patients responded to a questionnaire developed for this study.
      RESULTS: The majority of participants considered that terminally ill patients
      should know about their prognosis. Although nearly all nurses said that when a
      patient brings up the subject and they talk with the patient about death, several
      of the nurses find it difficult to establish a relationship with these patients.
      Concerning nurses' perception about physicians' actions, they considered that
      physicians avoid the subject of death with their patients more than the
      physicians acknowledge. CONCLUSIONS: More education and training of physicians
      and nurses on end-of-life issues is needed to improve communication with dying
      patients and to provide them with better care.

PMID- 29451638
TI  - [Association between health anthropometric indexes with physical fitness in
      physically active elderly women].
AB  - OBJECTIVE: To associate health anthropometric indexes with physical fitness of
      elderly women (EW) who participate in physical exercise workshops. MATERIALS AND
      METHODS: 272 Chilean women over 60 years took part in the study. The variables
      studied were BMI, waist circumference (WC), waist-height index (WHI) and physical
      fitness (PF). Correlations were made through the Pearson or Spearman coefficient,
      and bivariate associations using Pearson's Chi-square and the Fisher's exact
      test, considering p<0.05. RESULTS: 70.8% of the EW were overweight or obese;
      68.8% and 96% were at cardiometabolic risk due to their WC and WHI, respectively.
      Their PF showed equal performance (53.5%) or higher (33.8%) according to their
      age and gender. Inverse correlations were found between nutritional status and
      cardiometabolic risk with PF tests (except for agility and dynamic balance
      [direct]), and direct association with back scratch test. CONCLUSIONS: Excess
      weight in physically active EW would not affect their physical-functional
      performance; however, cardiometabolic risk would be inversely associated with
      motor function.

PMID- 29451639
TI  - [Analysis of foods advertised to childhood audience on chilean television].
AB  - OBJECTIVE: To examine food advertising aimed at childhood's audience broadcast on
      Chilean television. MATERIALS AND METHODS: Cross-sectional study. Food
      advertising broadcast by 4 open signal TV channels was recorded for 12 hours
      daily on twelve days randomly selected. Notices were classified according to food
      groups and level of processing. The frequency of food advertisement aimed to
      childhood audience was compared with those for adults. Nutrient profile of foods
      advertised was described. RESULTS: In 144 hours of recording appeared 530 food
      advertisement; 53.2% were aimed to childhood audience. The most advertised foods
      were sugary dairy (28.4%), sweetened beverages (25.5%), and sweetened cereals
      (17.7%). Of the foods advertised to childhood audience, 75% exceeds the criterion
      for free sugars. CONCLUSIONS: Chilean television advertises ultra-processed foods
      that exceed the limits of free sugars.

PMID- 29451640
TI  - Glucose level evaluation in monopedicled rectus abdominis myocutaneous flap after
      venous occlusion: experimental study in rats.
AB  - OBJECTIVE: to validate an experimental model for the measurement of glycemic
      levels in surgical flaps with the use of common glucometers, and to analyze the
      diagnostic criteria for hypoperfusion of such flaps. METHODS: we performed
      vertical myocutaneous rectus abdominis flaps with upper pedicles bilaterally in
      20 male Wistar rats, divided into two groups: with and without venous occlusion
      of the pedicle. We measured glucose levels in the flaps and in the systemic
      circulation with standard glucometers. We tested the accuracy of alternative
      diagnostic criteria for the detection of hypoperfusion. RESULTS: from 15 minutes
      of venous occlusion on, there was a significant reduction in glucose levels
      measured in the congested flap (p<0.001). Using a minimum difference of 20mg/dl
      in the glycemic levels between the flap and systemic blood, 30 minutes after
      occlusion, as a diagnostic criterion, the sensitivity was 100% (95% CI 83.99
      100%) and specificity of 90% (95% CI 69.90-97.21%) for the diagnosis of flap
      congestion. CONCLUSION: It is possible to measure glucose levels in vertical
      myocutaneous rectus abdominis flaps of Wistar rats, perfused or congested, using
      a common glucometer. The diagnostic criteria that compare the glucose levels in
      the flaps with the systemic ones were more accurate in the evaluation of tissue
      perfusion.

PMID- 29451642
TI  - Damage control surgery: are we losing control over indications?
AB  - OBJECTIVE: to analyze the surgeons' subjective indications for damage control
      surgery, correlating with objective data about the patients' physiological state
      at the time the surgery was chosen. METHODS: we carried out a prospective study
      between January 2016 and February 2017, with 46 trauma victims who were submitted
      to damage control surgery. After each surgery, we applied a questionnaire to the
      attending surgeon, addressing the motivations for choosing the procedure. We
      collected data in the medical records to assess hemodynamic conditions, systolic
      blood pressure and heart rate on arrival at the emergency room (grade III or IV
      shock on arrival at the emergency room would partially justify the choice). We
      considered elevation of serum lactate level, prolonged prothrombin time and blood
      pH below 7.2 as laboratory indicators of worse prognosis, objectively
      corroborating the subjective choice of the procedure. RESULTS: the main
      indications for damage control surgery were hemodynamic instability (47.8%) and
      high complexity lesions (30.4%). Hemodynamic and laboratory changes corroborated
      the choice in 65.2% of patients, regardless of the time; 23.9% presented
      hemodynamic changes compatible with degree III and IV shock, but without
      laboratory alterations; 4.3% had only laboratory abnormalities and 6.5% had no
      alterations at all. CONCLUSION: in the majority of cases, there was early
      indication for damage control surgery, based mainly on hemodynamic status and
      severity of lesions, and in 65.2%, the decision was compatible with alterations
      in objective hemodynamic and laboratory data.

PMID- 29451641
TI  - Splenic implant preservation after conservation in lactated Ringer's solution.
AB  - OBJECTIVE: to evaluate the morphology and function of autogenous splenic tissue
      implanted in the greater omentum, 24 hours after storage in Ringer-lactate
      solution. METHODS: we divided 35 male rats into seven groups (n=5): Group 1: no
      splenectomy; Group 2: total splenectomy without implant; Group 3: total
      splenectomy and immediate autogenous implant; Group 4: total splenectomy,
      preservation of the spleen in Ringer-lactate at room temperature, then sliced and
      implanted; Group 5: total splenectomy, spleen sliced and preserved in Ringer
      lactate at room temperature before implantation; Group 6: total splenectomy with
      preservation of the spleen in Ringer-lactate at 4 degrees C and then sliced and
      implanted; Group 7: total splenectomy and the spleen sliced for preservation in
      Ringer-lactate at 4 degrees C before implantation. After 90 days, we performed
      scintigraphic studies with Tc99m-colloidal tin (liver, lung, spleen or implant
      and clot), haematological exams (erythrogram, leucometry, platelets), biochemical
      dosages (protein electrophoresis) and anatomopathological studies. RESULTS:
      regeneration of autogenous splenic implants occurred in the animals of the groups
      with preservation of the spleen at 4oC. The uptake of colloidal tin was higher in
      groups 1, 3, 6 and 7 compared with the others. There was no difference in
      hematimetric values in the seven groups. Protein electrophoresis showed a
      decrease in the gamma fraction in the group of splenectomized animals in relation
      to the operated groups. CONCLUSION: the splenic tissue preserved in Ringer
      lactate solution at 4oC maintains its morphological structure and allows
      functional recovery after being implanted on the greater omentum.

PMID- 29451643
TI  - The applicability of POSSUM and P-POSSUM scores as predictors of morbidity and
      mortality in colorectal surgery.
AB  - OBJECTIVE: to apply the POSSUM and P-POSSUM scores as a tool to predict morbidity
      and mortality in colorectal surgery. METHODS: we conducted a prospective cohort
      study of 551 patients submitted to colorectal surgery in a colorectal surgery
      tertiary referral hospital in Brazil. We grouped patients into pre-established
      risk categories for comparison between expected and observed morbidity and
      mortality rates by the POSSUM and P-POSSUM scores. RESULTS: in the POSSUM
      morbidity analysis, the overall expected morbidity was significantly higher than
      that observed (39.2% vs. 15.6%). The same occurred with patients grouped in
      categories II (28.9% x 10.5) and III (64.6% x 24.5%). In category I, the expected
      and observed morbidities were similar (13.7% x 9.1%). Regarding the evaluation of
      mortality, it was statistically higher than that observed in category III
      patients and in the total number of patients (11.3% vs. 5.6%). In categories I
      and II, we observed the same pattern of category III, but without statistical
      significance. When evaluating mortality by the P-POSSUM score, the overall
      expected and observed mortality was similar (5.8% x 5.6%). Of the 31 patients who
      died, 20.2% underwent emergency procedures and sepsis was the main cause of
      death. CONCLUSION: the P-POSSUM score was an accurate tool to predict mortality
      and could be safely used in this population profile, unlike the POSSUM score.

PMID- 29451644
TI  - Scrotal reconstruction with superomedial fasciocutaneous thigh flap.
AB  - OBJECTIVE: to describe the use of a superomedial fasciocutaneous thigh flap for
      scrotal reconstruction in open areas secondary to the surgical treatment of
      perineal necrotizing fasciitis (Fournier's gangrene). METHODS: retrospective
      analysis of cases treated at the Plastic Surgery Service of Santa Casa de
      Misericordia, Sao Paulo, from 2009 to 2015. RESULTS: fifteen patients underwent
      scrotal reconstruction using the proposed flap. The mean age was 48.9 years (28
      to 66). Skin loss estimates in the scrotal region ranged from 60 to 100%.
      Definitive reconstruction was performed on average 30.6 days (22 to 44) after the
      initial surgical treatment. The mean surgical time was 76 minutes (65 to 90) to
      obtain the flaps, bilateral in all cases. Flap size ranged from 10cm to 13cm in
      the longitudinal direction and 8cm to 10cm in the cross-sectional direction. The
      complication rate was 26.6% (four cases), related to the occurrence of segmental
      and partial dehiscence. CONCLUSION: the superomedial fasciocutaneous flap of
      thigh is a reliable and versatile option for the reconstruction of open areas in
      the scrotal region, showing adequate esthetic and functional results.

PMID- 29451645
TI  - Intragastric balloons in high-risk obese patients in a Brazilian center: initial
      experience.
AB  - OBJECTIVE: to assess the short-term efficacy, tolerance and complications in high
      risk morbidly obese patients treated with an intragastric balloon as a bridge for
      surgery. METHODS: we conducted a post-hoc analysis study in a Brazilian teaching
      hospital from 2010 to 2014, with 23 adult patients with a BMI of 48kg/m2, who
      received a single intragastric air or liquid balloon. We defined efficacy as 10%
      excess weight loss, and complications, as adverse events consequent to the
      intragastric balloon diagnosed after the initial accommodative period. We
      expressed the anthropometric results as means +/- standard deviation, comparing
      the groups with paired T / Student's T tests, when appropriate, with p<0.05
      considered statistically significant. RESULTS: the balloons were effective in
      91.3% of the patients, remained in situ for an average of 5.5 months and most of
      them (65.2%) were air-filled, with a mean excess weight loss of 23.7kg+/-9.7
      (excess weight loss 21.7%+/-8.9) and mean BMI reduction of 8.3kg/m2+/-3.3.
      Complications (17.3%) included abdominal discomfort, balloon deflation and late
      intolerance, without severe cases. Most of the participants (82.7%) did not
      experience adverse effects. We removed the intragastric balloons in time, without
      intercurrences, and 52.2% of these patients underwent bariatric surgery within
      one month. CONCLUSION: in our center, intragastric balloons can be successfully
      used as an initial weight loss procedure, with good tolerance and acceptable
      complications rates.

PMID- 29451646
TI  - Profile of patients with Fournier's gangrene and their clinical evolution.
AB  - OBJECTIVE: to analyze the profile of patients with Fournier's gangrene treated in
      a public tertiary hospital in western Parana State. METHODS: we conducted a cross
      sectional, retrospective and descriptive study of patients with Fournier's
      gangrene treated between January 2012 and November 2016. RESULTS: there were 40
      patients with Fournier's gangrene treated in the period, 29 (72.5%) men and 11
      (27.5%) women. The mean age was 51.7+/-16.3 years. The mean time of disease
      progression, from the initial symptom to hospitalization, was 10.5+/-1.2 days.
      All patients had clinical signs such as pain, bulging, erythema, among others,
      and 38 (95%) had associated comorbidities, the most common being type 2 diabetes
      mellitus and systemic arterial hypertension. The majority (30 patients - 75%) had
      perianal abscess as the probable etiology. All patients were submitted to
      antibiotic therapy and surgical treatment, with a mean of 1.8+/-1.1 surgeries per
      patient. Nine (22.5%) patients died. There was a strong correlation between the
      presence of sepsis on admission and mortality. CONCLUSION: Fournier's gangrene
      patients in this series had a long disease duration and a high prevalence of
      comorbidities, with a high mortality rate.

PMID- 29451647
TI  - Criopreserved ovarian tissue transplantation and bone restoration metabolism in
      castrated rats.
AB  - OBJECTIVES: to evaluate estradiol levels and autotransplantation heated ovarian
      tissue effects, after vitrification, on rats bone metabolism previously
      oophorectomized bilaterally. METHODS: experimental study with 27 rats aged 11 to
      12 weeks and weighing 200g to 300g, submitted to bilateral oophorectomy and
      ovarian tissue cryopreservation for subsequent reimplantation. Animals were
      divided into two groups, A and B, with 8 and 19 rats, respectively.
      Autotransplantation occurred in two periods according to castration time: after
      one week, in group A, and after one month in group B. Serum estradiol
      measurements and ovary and tibia histological analysis were performed before and
      after oophorectomy period (early or late) and one month after reimplantation.
      RESULTS: in groups A and B, tibia median cortical thickness was 0.463+/-0.14mm
      (mean+/-SD) at the baseline, 0.360+/-0.14mm after oophorectomy and 0.445+/-0.17mm
      one month after reimplantation p<0.005). Trabecular means were 0.050+/-0.08mm
      (mean+/-SD) at baseline, 0.022+/-0.08mm after oophorectomy and 0.049+/-0.032mm
      one month after replantation (p<0.005). There was no statistical difference in
      estradiol variation between the two study groups (p=0.819). CONCLUSION:
      cryopreserved ovarian tissue transplantation restored bone parameters, and these
      results suggest that ovarian reimplantation in women may have the same beneficial
      effects on bone metabolism.

PMID- 29451648
TI  - 3-D finite element analysis of the effects of post location and loading location
      on stress distribution in root canals of the mandibular 1st molar.
AB  - Objective The purpose of this study was to evaluate, by using finite element
      analysis, the influence of post location and occlusal loading location on the
      stress distribution pattern inside the root canals of the mandibular 1st molar.
      Material and Methods Three different 3-D models of the mandibular 1st molar were
      established: no post (NP) - a model of endodontic and prosthodontic treatments;
      mesiobuccal post (MP) - a model of endodontic and prosthodontic treatments with a
      post in the mesiobuccal canal; and distal post (DP) - a model of endodontic and
      prosthodontic treatments with a post in the distal canal. A vertical force of 300
      N, perpendicular to the occlusal plane, was applied to one of five 1 mm2 areas on
      the occlusal surface; mesial marginal ridge, distal marginal ridge, mesiobuccal
      cusp, distobuccal cusp, and central fossa. Finite element analysis was used to
      calculate the equivalent von Mises stresses on each root canal. Results The DP
      model showed similar maximum stress values to the NP model, while the MP model
      showed markedly greater maximum stress values. The post procedure increased
      stress concentration inside the canals, although this was significantly affected
      by the site of the force. Conclusions In the mandibular 1st molar, the distal
      canal is the better place to insert the post than the mesiobuccal canal. However,
      if insertion into the mesiobuccal canal is unavoidable, there should be
      consideration on the occlusal contact, making central fossa and distal marginal
      ridge the main functioning areas.

PMID- 29451649
TI  - The effects of different restorative materials on periodontopathogens in combined
      restorative-periodontal treatment.
AB  - Objective The aim of the study was to evaluate the association between
      subgingival restorations and the target periodontopathogenic bacteria (Pg, Td and
      Pi) in subgingival biofilm during one year after combined restorative-periodontal
      treatment. Material and Methods Seventeen systemically healthy subjects, who were
      positive for the presence of three cervical lesions associated with gingival
      recessions in three different adjacent teeth, were included in the study. A total
      of 51 combined defects were treated with connective tissue graft plus a
      nanofilled composite resin (NCR+CTG), a resin-modified glass ionemer cement
      (RMGI+CTG) and a fluoride-releasing resin material with pre-reacted glass (PRG),
      called giomer (Giomer+CTG). Periodontal clinical measurements and subgingival
      plaque samples were obtained from all combined defects at baseline and at 6 and
      12 months after the surgery. The number of bacteria were evaluated by the real
      time polymerase chain reaction (qPCR) method. Results No statistically
      significant difference in the amount of DNA copies of Pg, Td and Pi was observed
      in any of the groups at any time points (p>0.05). In addition, there was no
      statistically significant difference in the amount of DNA copies of the bacteria
      at baseline and at 6 and 12 months postoperatively, regardless of treatment group
      (p>0.05). Conclusion This study suggests that subgingivally placed NCR, RMGI and
      giomer restorations can show similar effects on periodontopathogenic bacteria in
      the treatment of gingival recessions that are associated with noncarious cervical
      lesions (NCCLs).

PMID- 29451650
TI  - Comparison of deflection forces of esthetic archwires combined with ceramic
      brackets.
AB  - Coated archwires and ceramic brackets have been developed to improve facial
      esthetics during orthodontic treatment. However, their mechanical behavior has
      been shown to be different from metallic archwires and brackets. Therefore, the
      aim of this study was to compare the deflection forces in coated nickel-titanium
      (NiTi) and esthetic archwires combined with ceramic brackets. Material and
      Methods Non-coated NiTi (NC), rhodium coated NiTi (RC), teflon coated NiTi (TC),
      epoxy coated NiTi (EC), fiber-reinforced polymer (FRP), and the three different
      conventional brackets metal-insert polycrystalline ceramic (MI-PC),
      polycrystalline ceramic (PC) and monocrystalline ceramic (MC) were used. The
      specimens were set up on a clinical simulation device and evaluated in a
      Universal Testing Machine (Instron). An acrylic device, representative of the
      right maxillary central incisor was buccolingually activated and the unloading
      forces generated were recorded at 3, 2, 1 and 0.5 mm. The speed of the testing
      machine was 2 mm/min. ANOVA and Tukey tests were used to compare the different
      archwires and brackets. Results The brackets presented the following decreasing
      force ranking: monocrystalline, polycrystalline and polycrystalline metal-insert.
      The decreasing force ranking of the archwires was: rhodium coated NiTi (RC), non
      coated NiTi (NC), teflon coated NiTi (TC), epoxy coated NiTi (EC) and fiber
      reinforced polymer (FRP). At 3 mm of unloading the FRP archwire had a plastic
      deformation and produced an extremely low force in 2; 1 and 0.5 mm of unloading.
      Conclusion Combinations of the evaluated archwires and brackets will produce a
      force ranking proportional to the combination of their individual force rankings.

PMID- 29451652
TI  - Animal experimentation: A look into ethics, welfare and alternative methods.

PMID- 29451651
TI  - Demetallization of Enterococcus faecalis biofilm: a preliminary study.
AB  - Objectives To determine the concentration of calcium, iron, manganese and zinc
      ions after the application of chelator to Enterococcus faecalis biofilms.
      Material and Methods Fifty bovine maxillary central incisors were prepared and
      inoculated with E. faecalis for 60 days. The following were used as irrigation
      solutions: 17% EDTA (pH 3, 7 and 10), 2.5% sodium hypochlorite (NaOCl) combined
      with 17% EDTA (pH 3, 7 and 10), distilled water (pH 3, 7 and 10), and 2.5% NaOCl.
      Each solution was kept in the root canal for five minutes. Fifteen uncontaminated
      root canals were irrigated with 17% EDTA (pH 3, 7 and 10). Six teeth were used as
      bacterial control. The number of calcium, iron, manganese and zinc ions was
      determined using flame atomic absorption spectrometry. Mean +/- standard
      deviation (SD) values were used for descriptive statistics. Results Calcium
      chelation using 17% EDTA at pH 7 was higher than at pH 3 and 10, regardless of
      whether bacterial biofilm was present. The highest concentration of iron occurred
      at pH 3 in the presence of bacterial biofilm. The highest concentration of
      manganese found was 2.5% NaOCl and 17% EDTA at pH 7 in the presence of bacterial
      biofilm. Zinc levels were not detectable. Conclusions The pH of chelating agents
      affected the removal of calcium, iron, and manganese ions. The concentration of
      iron ions in root canals with bacterial biofilm was higher after the use of 17%
      EDTA at pH 3 than after the use of the other solutions at all pH levels.

PMID- 29451653
TI  - Benign prostatic hyperplasia: laser prostatectomy (PVP).

PMID- 29451654
TI  - Fulminant myocarditis in children. Continuous renal replacement therapy to the
      rescue?

PMID- 29451655
TI  - Human polyomavirus infection: Cytological and molecular diagnosis.
AB  - Few studies directly compare urinary cytology with molecular methods for
      detecting BK and JC polyomaviruses. Reactivation of BKV infection is the main
      risk factor for the development of nephropathy in immunocompromised individuals.
      The limitation of the cytological method can be attributed to the stage where the
      infected cell does not have specific and sufficient morphological characteristics
      for a conclusive diagnosis and can be easily interpreted as degenerative
      alteration. Moreover, morphologically, it is not possible to differentiate the
      two types of viruses. Polymerase chain reaction (PCR), not only is a sensitive
      method, but also allows differentiation of viral types without quantification,
      and therefore is not indicative of nephropathy. According to the American Society
      of Nephrology, real-time PCR would be the gold standard to indicate nephropathy
      because it allows quantifying the number of viral copies.

PMID- 29451656
TI  - Posterior fossa decompression with duraplasty in Chiari surgery: A technical
      note.
AB  - Chiari malformation (CM) is the most common and prevalent symptomatic congenital
      craniocervical malformation. Radiological diagnosis is established when the
      cerebellar tonsils are located 5 mm or more below the level of the foramen magnum
      on magnetic resonance imaging (MRI). Surgical treatment is indicated whenever
      there is symptomatic tonsillar herniation or syringomyelia/hydrocephalus. The
      main surgical treatment for CM without craniocervical instability (such as
      atlantoaxial luxation) is posterior fossa decompression, with or without
      duraplasty. The authors describe in details and in a stepwise fashion the
      surgical approach of patients with CM as performed at the State University of
      Campinas, emphasizing technical nuances for minimizing the risks of the procedure
      and potentially improving patient outcome.

PMID- 29451657
TI  - Malignant fibrous histiocytoma in a patient presenting with urinary system
      symptoms.
AB  - Malignant fibrous histiocytoma is a rare tumor. It is most commonly seen in
      individuals between the fifth and seventh decades of life, in extremities, and
      less frequently in the retroperitoneum. Although its etiology is not clearly
      known, radiotherapy, chemical agents, previous history of surgery, trauma and
      fracture, and Hodgkin lymphoma have been blamed. Leiomyosarcoma, liposarcoma and
      rhabdomyosarcoma should be taken into account in differential diagnosis. It is
      seen on computed tomography as a mass lesion with irregular borders and density
      similar to that of the surrounding muscle tissue. Necrotic and hemorrhagic
      components in the mass are characterized as heterogeneous low density areas.
      Fluid-fluid levels can be detected by computed tomography and magnetic resonance
      imaging.

PMID- 29451658
TI  - Clinical correlation of biopsy results in patients with temporal arteritis.
AB  - OBJECTIVE: Temporal arteritis is systemic vasculitis of medium and large sized
      vessels. The lowest incidence rates were reported in Turkey, Japan and Israel. We
      aimed to investigate the results of patients with biopsy-proven temporal
      arteritis and those classified according to the American College of Rheumatology
      criteria from a low-incidence region for temporal arteritis. The results of our
      study are noteworthy, since there is limited data on pathologic diagnosis of
      temporal arteritis in Turkey. METHOD: We studied the medical records, laboratory
      findings such as erythrocyte sedimentation rate and C-reactive protein levels,
      biopsy results, and postoperative complications of all the patients operated for
      temporal artery biopsy at our clinic. We used the computerized laboratory
      registry that keeps all records of 42 consecutive temporal artery biopsy results
      from January 2011 to December 2016. RESULTS: The mean age was 66+/-12.5 years.
      The most common manifestations on admission were temporal headache, optic
      neuritis and jaw claudication, respectively. Temporal artery biopsy  results
      confirmed tempoal arteritis in eight out of 42 (19%) patients. There was no
      statistically significant difference between biopsy-positive and biopsy-negative
      groups in terms of sex, age, erythrocyte sedimentation rate, C-reactive protein
      and biopsy length. CONCLUSION: We were not able to find a correlation between the
      analysis of biopsy results and clinical evaluation of patients with temporal
      arteritis. We suggest that diagnosis of temporal arteritis  depends on clinical
      suspicion. Laboratory examination results may not be helpful in accurate
      diagnosis of tempoal arteritis.

PMID- 29451659
TI  - Environmental factors can influence dengue reported cases.
AB  - INTRODUCTION: Global climate changes directly affect the natural environment and
      contribute to an increase in the transmission of diseases by vectors. Among these
      diseases, dengue is at the top of the list. The aim of our study was to
      understand the consequences of temporal variability of air temperature in the
      occurrence of dengue in an area comprising seven municipalities of the Greater
      Sao Paulo. METHOD: Characterization of a temporal trend of the disease in the
      region between 2010 and 2013 was performed through analysis of the notified
      number of dengue cases over this period. Our analysis was complemented with
      meteorological (temperature) and pollutant concentration data (PM10). RESULTS: We
      observed that the months of January, February, March, April and May (from 2010 to
      2013) were the ones with the highest number of notified cases. We also found that
      there is a statistical association of moisture and PM10 with the reported cases
      of dengue. CONCLUSION: Although the temperature does not statistically display an
      association with recorded cases of dengue, we were able to verify that
      temperature peaks coincide with dengue outbreak peaks. Future studies on
      environmental pollution and its influence on the development of Aedes aegypti
      mosquito during all stages of its life cycle, and the definition of strategies
      for better monitoring, including campaigns and surveillance, would be compelling.

PMID- 29451660
TI  - Economic assessment of postoperative pain control strategies for treatment of
      adult patients with cancer.
AB  - OBJECTIVE: The authors performed an economic assessment of opioids currently
      being used for control of postoperative pain relating to the surgical treatment
      of cancer (fentanyl and sufentanil) within the Brazilian Unified Health System
      (SUS, in the Portuguese acronym). METHOD: The assessment was based on the
      perspective of the government, in order to collaborate with the promotion of
      effectiveness in public policies of health, and to optimize the allocation of
      public resources into health. A cost-effectiveness analysis was performed using
      data collected from the Brazilian Unified Health System and information from
      literature review, in order to build a decision tree on the alternatives for
      control of postoperative pain related to cancer treatment among adult patients.
      The outcomes considered were: effectiveness of postoperative analgesia and
      occurrence of nausea and vomit in the 48 hour period after surgery, and
      additional 24-hour cycles in patient follow-up. A univariate sensitivity analysis
      was conducted in order to verify robustness of the model estimated. RESULTS:
      Literature review showed a limited number of studies directly comparing fentanyl
      and sufentanil for control of postoperative pain. The adoption of sufentanil
      (cost = U$ 25.72 / outcome = 1.6 VAS points) was dominant in relation to the use
      of fentanyl (cost = U$ 32.58 / outcome = 2.6 VAS points). The estimated model
      showed robustness in relation to changes in the parameters analyzed. CONCLUSION:
      Sufentanil presented higher cost-effectiveness ratio in relation to fentanyl for
      control of postoperative pain in surgeries related to cancer treatment among
      adult patients in the Brazilian Unified Health System.

PMID- 29451661
TI  - Association between the RAGE (receptor for advanced glycation end-products) 
      374T/A gene polymorphism and diabetic retinopathy in T2DM.
AB  - OBJECTIVE: Interaction between advanced glycation end-products (AGEs) and
      receptor for AGEs (RAGE) in cells could affect both extracellular and
      intracellular structure and function, which plays a pivotal role in diabetic
      microvascular complications. The results from previous epidemiological studies on
      the association between RAGE gene -374T/A polymorphism and diabetic retinopathy
      (DR) risk were inconsistent. Thus, we conducted this meta-analysis to summarize
      the possible association between RAGE -374T/A polymorphism and DR risk. METHOD:
      We searched all relevant articles on the association between RAGE -374T/A
      polymorphism and DR risk from PubMed, Cochrane Library, ScienceDirect, Wanfang,
      VIP and Chinese National Knowledge Infrastructure (CNKI) web databases up to
      August 2016. Odds ratio (OR) with 95% confidence interval (CI) were calculated to
      assess those associations. All analyses were performed using the Review Manager
      software. RESULTS: Nine case-control studies, including 1,705 DR cases and 2,236
      controls were enrolled, and the results showed that the A allele of RAGE -374T/A
      polymorphism was significantly associated with increased DR risk in dominant
      model (TA/AA vs. TT: OR=1.22, 95CI 1.05-1.41, p=0.006) and heterozygote model (TA
      vs. TT: OR=1.26, 95CI 1.07-1.47, p=0.005). The subgroup analysis by ethnicity
      showed that significantly increased DR risk was found in both Asian and Caucasian
      populations. CONCLUSION: This meta-analysis reveals that the A allele of RAGE 
      374T/A polymorphism probably increase DR risk.

PMID- 29451662
TI  - What clinical, functional, and psychological factors before treatment are
      predictors of poor quality of life in cancer patients at the end of chemotherapy?
AB  - OBJECTIVE: To correlate physical activity level (PAL), functional capacity and
      psychological state with quality of life (QoL) in cancer patients undergoing
      chemotherapy (CT). METHOD: Observational cohort study. Patients (n=121) with any
      primary cancer site with indications of chemotherapy with palliative or curative
      intent were evaluated at three moments: 1) patient admission (week 0), before
      chemotherapy; 2) week 8; 3) end of CT. Data were collected regarding QoL, PAL,
      clinical data, functional capacity (short walking distance test, sitting-rising
      test, isometric manual gripping force), and anxiety and depression tests.
      RESULTS: There was significant improvement at the end of CT for: level of
      physical activity; walk test (> 500 meters); sitting-rising test (> 20x). There
      was a significant reduction in the prevalence of moderate/severe depression. The
      prevalence of high QoL showed a significant increase in evaluation 3 (42.4% vs.
      40.0% vs. 59.2%, p=0.02). Education up to high school level, low PAL, walking <
      300 meters, sitting and rising < 20 times, having depression (moderate to severe)
      and QoL that was not high at the start of treatment (week 0) all proved to be
      risk factors for low quality of life at week 16. Conversely, early staging,
      curative intent chemotherapy and low-grade symptoms were shown to be protective
      factors. CONCLUSION: Performing less than 20 movements in the sitting-rising test
      and low PAL at the start of chemotherapy represent independent risk factors for
      low quality of life at the end of chemotherapy.

PMID- 29451663
TI  - The analysis on the expression of gasotransmitters in early trauma patients.
AB  - OBJECTIVE: Nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S)
      were endogenously-generated molecules gas. They owned important biological
      activity and participated in many pathophysiological processes. This study aimed
      to examine the levels of three gasotransmitters in the early phase of trauma
      patients. METHOD: Blood samples were collected from 60 trauma patients and ten
      healthy volunteers. Concentration of serum iNOS and HO-1 were analyzed by enzyme
      linked immunosorbent assay and plasma H2S was determined by colorimetric method.
      Meanwhile, the occurrence of multiple organ dysfunction syndrome (MODS) was also
      monitored. RESULTS: The levels of iNOS, HO-1 and endogenous H2S in the patients
      group were significantly different from the healthy control group, and the
      difference was more obvious with the increase of ISS score. iNOS levels were
      positively correlated with ISS scores and blood lactic acid values, and HO-1 and
      endogenous H2S were negatively correlated with ISS scores and blood lactic acid
      values. Of 60 trauma patients, eight (13.33%) developed MODS. The level of iNOS
      in the MODS group was higher than that in non-MODS group, while HO-1 and H2S were
      significant lower in the MODS group. CONCLUSION: The three gasotransmitters
      participated in systemic inflammatory responses during early trauma and could be
      used as important indicators for trauma severity. Their measurements were
      meaningful for evaluating the severity and prognosis of trauma.

PMID- 29451664
TI  - Update on antiphospholipid antibody syndrome.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease characterized by
      antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy
      morbidity. Most APS events are directly related to thrombotic events, which may
      affect small, medium or large vessels. Other clinical features like
      thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction and
      skin ulcers (called non-criteria manifestations) add significant morbidity to
      this syndrome and represent clinical situations that are challenging. APS was
      initially described in patients with systemic lupus erythematosus (SLE) but it
      can occur in patients without any other autoimmune disease. Despite the
      autoimmune nature of this syndrome, APS treatment is still based on
      anticoagulation and antiplatelet therapy.

PMID- 29451665
TI  - Mirror therapy: A potential intervention for pain management.
AB  - The consequences of chronic pain and associated disabilities to the patient and
      to the health care system are well known. Medication is often the first treatment
      of choice for chronic pain, although side effects and high costs restrict long
      term use. Inexpensive, safe and easy to self-administer non-pharmacological
      therapies, such as mirror therapy, are recommended as adjuncts to pain treatment.
      The purpose of this review is to describe the principles of use of mirror therapy
      so it can be incorporated into a health care delivery. The physiological
      rationale of mirror therapy for the management of pain and the evidence of
      clinical efficacy based on recent systematic reviews are also discussed. Mirror
      therapy, whereby a mirror is placed in a position so that the patient can view a
      reflection of a body part, has been used to treat phantom limb pain, complex
      regional pain syndrome, neuropathy and low back pain. Research evidence suggests
      that a course of treatment (four weeks) of mirror therapy may reduce chronic
      pain. Contraindications and side effects are few. The mechanism of action of
      mirror therapy remains uncertain, with reintegration of motor and sensory
      systems, restored body image and control over fear-avoidance likely to influence
      outcome. The evidence for clinical efficacy of mirror therapy is encouraging, but
      not yet definitive. Nevertheless, mirror therapy is inexpensive, safe and easy
      for the patient to self-administer.

PMID- 29451666
TI  - Pilates for breast cancer: A systematic review and meta-analysis.
AB  - INTRODUCTION: Breast cancer is the leading type of cancer causing death in women
      worldwide. The incidence of the disease is expected to grow worldwide due to the
      aging of the population and risk factors related to lifestyle behaviors.
      Considering the lifestyle of women with breast cancer before or after surgery,
      pilates exercise may be a complementary intervention additionally to standard
      treatment. OBJECTIVE: To analyze the efficacy of pilates compared to other
      exercises and to no exercise for women with breast cancer diagnosis. METHOD: We
      searched Medline via Pubmed, Embase via Ovid, Amed via EBSCO, Biosis via Ovid,
      Lilacs and the Cochrane Library for relevant publications until March 2017. The
      keywords used were pilates and "breast cancer," and only randomized controlled
      trials were included. Critical appraisal was done using Risk of Bias Tool and
      GRADE score for assessing the quality of evidence. RESULTS: A total of five
      studies were included in our review. Our results demonstrate that pilates or home
      based exercises are better than no exercise in each individual study. We observed
      significant improvements in the pilates groups compared to home-based exercises.
      Additionally, in the individual studies, we observed improvements in range of
      motion, pain and fatigue. CONCLUSION: The evidence shows that pilates or home
      based exercise should be encouraged to women with breast cancer.

PMID- 29451667
TI  - Approach to concurrent coronary and carotid artery disease: Epidemiology,
      screening and treatment.
AB  - The concomitance between coronary artery disease and carotid artery disease is
      known and well documented. However, it is a fact that, despite the screening
      methods for these conditions and the advances in surgical treatment, little has
      been achieved in terms of reducing the risk of complications in the perioperative
      period. Publications are scarce, being mostly composed of reports or case series.
      There is little agreement on the best initial therapeutic approach (myocardial
      versus carotid revascularization) or the best technique to be used (surgery with
      or without extracorporeal circulation, hybrid treatments, etc.). The authors
      performed a review of the evidence in this clinical scenario, raising pragmatic
      questions that help in the therapeutic decision.

PMID- 29451668
TI  - Comparison between early and delayed facial nerve decompression in traumatic
      facial nerve paralysis - A retrospective study.
AB  - Purpose To study the intraoperative findings in case of early and delayed
      decompression of facial nerve paralysis and compare their results. Methods
      Retrospective data analysis of 23 cases of longitudinal temporal bone fracture
      with House-Brackmann grade V and VI facial nerve paralysis. All cases were
      thoroughly evaluated and underwent facial nerve decompression through the
      transmastoid approach. All cases were under regular follow-up till the date of
      manuscript submission. Results Clinical improvement of the facial nerve function
      was observed for early vs. delayed facial nerve decompression. In the early
      decompression group, facial nerve function improved to grade II in eight cases
      (80%) and grade III in two cases (20%), whereas in the delayed decompression
      group it improved to grade II in one case (7.70%), grade III in four cases
      (30.76%), grade IV in seven cases (53.84%), and grade V in one case (7.70%).
      Conclusions Early decompression of facial nerve provides better results than
      delayed decompression because it enables early expansion of the nerve.

PMID- 29451669
TI  - Prosodic parameters of reading in 2nd to 5th grade students.
AB  - Purpose Characterize and compare melodic variation and reading speed and verify
      their evolution throughout the development of schooling. Methods The reading of
      78 Elementary School (2nd to 5th grade) students was analyzed using the Praat
      program with regards to the parameters of melodic variation (F0) and reading
      speed (Duration). Statistical measures (mean and standard deviation) were taken
      and the Student's t-test was applied at significance level of 5%. Results Melodic
      variation and reading speed increased as schooling progressed, especially during
      5th grade. Conclusion Melodic variation increases as schooling progresses, mainly
      during 5th grade. First minute of reading analysis is sufficient to assess
      reading speed, not being necessary to analyze the full text.

PMID- 29451670
TI  - 'It's a traumatic illness, traumatic to witness': a qualitative study of the
      experiences of bereaved family caregivers of patients with cutaneous T-cell
      lymphoma.
AB  - BACKGROUND: Cutaneous T-cell lymphomas (CTCL) are rare cancers, which can be
      difficult to diagnose, are incurable and adversely affect quality of life,
      particularly in advanced disease. Families often provide care, but little is
      known about their experiences or needs while caring for their relative with
      advanced disease or in bereavement. OBJECTIVES: To explore the experiences of
      bereaved family caregivers of patients with CTCL. METHODS: Single, semi
      structured qualitative interviews were conducted with bereaved family caregivers
      of patients with CTCL recruited via a supra-regional CTCL clinic. Transcribed
      interviews were analysed thematically, focusing on advanced disease, the approach
      of death and bereavement. RESULTS: Fifteen carers of 11 deceased patients
      participated. Experiences clustered under four themes: (1) complexity of care and
      medical intervention; (2) caregiver roles in advanced CTCL; (3) person-centred
      vs. organization-centred care in advanced CTCL and (4) knowing and not knowing:
      reflections on dying, death and bereavement. Caregivers often had vivid
      recollections of the challenges of caring for their relative with advanced CTCL
      and some took on quasi-professional roles as a result. Advanced disease made high
      demands on both organizational flexibility and family resources. For many
      caregivers, seeing disease progression was a prolonged and profoundly traumatic
      experience. The extent to which they were prepared for their relative's death and
      supported in bereavement was highly variable. Sub-themes within each theme
      provide more detail about caregiver experiences. CONCLUSIONS: Family caregivers
      should be considered part of the wider healthcare team, acknowledging their
      multiple roles and the challenges they encounter in looking after their relative
      with CTCL as the disease progresses. Their experiences highlight the importance
      of organizational flexibility and of good communication between healthcare
      providers in advanced CTCL.

PMID- 29451671
TI  - The validity of the diagnostic code for pyoderma gangrenosum in an electronic
      database.

PMID- 29451680
TI  - Evaluating the kinetic basis of plant growth from organs to ecosystems.
AB  - Contents Summary 37 I. Introduction 37 II. Predictions for metabolic kinetics 38
      III. Kinetics of net photosynthesis 38 IV. Kinetics of plant growth 40 V.
      Hypotheses for higher-level kinetic decoupling 41 VI. Conclusions 42
      Acknowledgements 42 References 42 SUMMARY: Understanding how temperature
      influences the scaling of physiological rates through levels of biological
      organization is critical for predicting plant responses to climate. Metabolic
      theory predicts that many rates increase exponentially with temperature following
      an activation energy (E) of 0.32 eV for photosynthesis. Here, I evaluate this
      prediction for net photosynthesis and organ, individual, and ecosystem growth.
      Observed E for photosynthesis varied widely but was not statistically different
      from predictions, while E for organs was greater than predicted, and E for
      individuals and ecosystems only weakly characterized temperature responses. I
      review several hypotheses that may underlie these results. Understanding how
      multiple rate-limiting processes coalesce into a single E that characterizes
      metabolic responses to temperature, and how to best estimate E from unimodal
      data, remain important challenges.

PMID- 29451672
TI  - Predictors of persistent prescription opioid analgesic use among people without
      cancer in Australia.
AB  - AIMS: To identify patterns of opioid analgesic use and determine predictors of
      persistent opioid use among people without cancer. METHODS: A population-based
      cohort study of Australians initiating prescription opioids from July 2013 to
      December 2015 was conducted using data from a random 10% sample of people who
      accessed medicines through Australia's Pharmaceutical Benefits Scheme. A 12-month
      retrospective period was used to define opioid initiation, exclude people with
      cancer and determine comorbidities. Persistent use over 12 months since
      initiation was identified through group-based trajectory modelling. Odds ratios
      (OR) and 95% confidence intervals (CIs) for predictors of opioid persistence were
      estimated using logistic regression. RESULTS: The cohort consisted of 431 963
      people without cancer who initiated opioids. A total of 11 323 (2.6%) persistent
      opioid users were identified. Predictors of persistence included initiation with
      transdermal formulations (OR 4.2, 95% CI 3.9-4.5), or initiation with total oral
      morphine equivalents (OME) >= 750 mg (3.7, 3.3-4.1), having depression (1.6, 1.5
      1.7) or psychotic illness (2.0, 1.9-2.2). Previous dispensing of paracetamol
      (2.0, 1.9-2.1), pregabalin (2.0, 1.8-2.1) and benzodiazepines (1.53, 1.4-1.6)
      predicted persistence. Compared to people aged 18-44 years, those >=75 years were
      2.5 (2.3-2.6) times more likely to be persistent users. CONCLUSIONS: Patient
      specific characteristics (older age, prior history of mental health comorbidities
      and use of non-opioid analgesics) and prescriber choice of initial opioid
      (transdermal formulation and higher total OMEs) were found to strongly predict
      persistent use. This information may help prescribers target monitoring and early
      intervention efforts in order to prevent harms associated with the long-term use
      of opioids.

PMID- 29451681
TI  - Verification of a physiologically based pharmacokinetic model of ritonavir to
      estimate drug-drug interaction potential of CYP3A4 substrates.
AB  - Ritonavir is one of several ketoconazole alternatives used to evaluate strong
      CYP3A4 inhibition potential in clinical drug-drug interaction (DDI) studies. In
      this study, four physiologically based pharmacokinetic (PBPK) models of ritonavir
      as an in vivo time-dependent inhibitor of CYP3A4 were created and verified for
      oral doses of 20, 50, 100 and 200 mg using the fraction absorbed (Fa ) and oral
      clearance (CLoral ) values reported in the literature, because transporter and
      CYP enzyme reaction phenotyping data were not available. The models were used
      subsequently to predict and compare the magnitude of the AUC increase in nine
      reference DDI studies evaluating the effect of ritonavir at steady-state on
      midazolam (CYP3A4 substrate) exposure. Midazolam AUC and Cmax ratios were
      predicted within 2-fold of the respective observations in seven studies.
      Simulations of the hepatic and gut CYP3A4 abundance after multiple oral dosing of
      ritonavir indicated that a 3-day treatment with ritonavir 100 mg twice daily is
      sufficient to reach maximal CYP3A4 inhibition and subsequent systemic exposure
      increase of a CYP3A4 substrate, resulting in the reliable estimation of fm,CYP3A4
      . The ritonavir model was submitted as part of the new drug application for
      Kisqali(r) (ribociclib) and accepted by health authorities.

PMID- 29451682
TI  - Metabolic regulation of leukocyte motility and migration.
AB  - Dynamic reorganization of the cytoskeleton is essential for numerous cellular
      processes including leukocyte migration. This process presents a substantial
      bioenergetic challenge to migrating cells as actin polymerization is dependent on
      ATP hydrolysis. Hence, migrating cells must increase ATP production to meet the
      increased metabolic demands of cytoskeletal reorganization. Despite this long
      standing evidence, the metabolic regulation of leukocyte motility and trafficking
      has only recently begun to be investigated. In this review, we will summarize
      current knowledge of the crosstalk between cell metabolism and the cytoskeleton
      in leukocytes, and discuss the concept that leukocyte metabolism may reprogram in
      response to migratory stimuli and the different environmental cues received
      during recirculation ultimately regulating leukocyte motility and migration.

PMID- 29451683
TI  - Prenatal diagnosis of anomalous origin of pulmonary artery.
AB  - BACKGROUND: Anomalous origin of the pulmonary arteries is a rare congenital
      pulmonary vascular malformation that includes unilateral absence of the pulmonary
      artery (UAPA), anomalous origin of unilateral pulmonary artery (AOPA), and left
      pulmonary artery sling (LPAS). METHODS: We analyze 15 cases of fetal pulmonary
      artery abnormalities from 2011 to 2017, detected via prenatal ultrasound at our
      center. RESULTS: The 15 cases include UAPA (5), AOPA (6), and LPAS (4). Of the
      UAPA cases, 2 had pulmonary atresia and 3 had pulmonary artery stenosis. In 5
      cases, the descending aorta issued collateral vessels to the left lung. Of the
      AOPA cases, 2 had left pulmonary artery abnormalities originating in the
      ascending aorta and 4 showed right pulmonary artery abnormalities originating in
      the ascending aorta. Of the LPAS cases, 2 were type IA, 1 was type IIA, and 1 was
      type IIB. Two of the LPAS were associated with right lung dysplasia. CONCLUSION:
      Abnormal origin of the pulmonary artery has a characteristic ultrasonographic
      appearance. The branch of the pulmonary artery cross section can provide
      important clues to the diagnosis of abnormal pulmonary artery origin. Pulmonary
      artery abnormalities are often associated with pulmonary atresia or stenosis.

PMID- 29451684
TI  - Intracellular pharmacokinetics of gemcitabine, its deaminated metabolite 2',2'
      difluorodeoxyuridine and their nucleotides.
AB  - AIMS: Gemcitabine (2',2'-difluoro-2'-deoxycytidine; dFdC) is a prodrug that has
      to be phosphorylated within the tumour cell to become active. Intracellularly
      formed gemcitabine diphosphate (dFdCDP) and triphosphate (dFdCTP) are considered
      responsible for the antineoplastic effects of gemcitabine. However, a major part
      of gemcitabine is converted into 2',2'-difluoro-2'-deoxyuridine (dFdU) by
      deamination. In the cell, dFdU can also be phosphorylated to its monophosphate
      (dFdUMP), diphosphate (dFdUDP) and triphosphate (dFdUTP). In vitro data suggest
      that these dFdU nucleotides might also contribute to the antitumour effects,
      although little is known about their intracellular pharmacokinetics (PK).
      Therefore, the objective of the present study was to gain insight into the
      intracellular PK of all dFdC and dFdU nucleotides formed during gemcitabine
      treatment. METHODS: Peripheral blood mononuclear cell (PBMC) samples were
      collected from 38 patients receiving gemcitabine, at multiple time points after
      infusion. Gemcitabine, dFdU and their nucleotides were quantified in PBMCs. In
      addition, gemcitabine and dFdU plasma concentrations were monitored. The
      individual PK parameters in plasma and in PBMCs were determined. RESULTS: Both in
      plasma and in PBMCs, dFdU was present in higher concentrations than gemcitabine
      [mean intracellular area under the concentration-time curve from time zero to 24
      h (AUC0-24 h ) 1650 vs. 95 MUM*h]. However, the dFdUMP, dFdUDP and dFdUTP
      concentrations in PBMCs were much lower than the dFdCDP and dFdCTP
      concentrations. The mean AUC0-24 h for dFdUTP was 312 MUM*h vs. 2640 MUM*h for
      dFdCTP. CONCLUSIONS: The study provides the first complete picture of all
      nucleotides that are formed intracellularly during gemcitabine treatment. Low
      intracellular dFdU nucleotide concentrations were found, which calls into
      question the relevance of these nucleotides for the cytotoxic effects of
      gemcitabine.

PMID- 29451685
TI  - A quantitative LC/MSMS method for determination of edoxaban, a Xa inhibitor and
      its pharmacokinetic application in patients after total knee arthroplasty.
AB  - Edoxaban was extracted from human plasma by simple protein precipitation with
      acetonitrile, followed by quantitative determination using a liquid
      chromatography-mass spectrometry method. The recoveries of edoxaban and the
      internal standard (ticlopidine) from human plasma were >85%, and the within- and
      between-day coefficients of variation were within 15%. The limit of
      quantification in human plasma was 1 ng/mL. The concentration of edoxaban in
      blood decreased at room temperature, but remained unchanged for 1 week at 4
      degrees C. On the other hand, the concentration in plasma at both -20 and -80
      degrees C remained unchanged for 5 months. These results indicated that blood
      samples should be centrifuged immediately or stored at 4 degrees C, and that
      plasma samples should be stored below -20 degrees C until analysis. This method
      was applied to human plasma obtained from four patients after total knee
      arthroplasty. Analysis of edoxaban pharmacokinetics demonstrated an absorption
      time lag of 4h, a maximum concentration of 110 +/- 26 ng/mL and an oral clearance
      of 37 +/- 16 L/h. The analytical methods established in this study will be
      suitable for determining the concentrations of edoxaban in human plasma.

PMID- 29451686
TI  - An iminium ion metabolite hampers the production of the pharmacologically active
      metabolite of a multikinase inhibitor KW-2449 in primates: irreversible
      inhibition of aldehyde oxidase and covalent binding with endogenous proteins.
AB  - We previously reported that KW-2449, (E)-1-{4-[2-(1H-Indazol-3
      yl)vinyl]benzoyl}piperazine, a novel multikinase inhibitor developed for the
      treatment of leukemia patients, was oxidized to an iminium ion intermediate by
      monoamine oxidase B (MAO-B) and then converted to its oxo-piperazine form (M1) by
      aldehyde oxidase (AO). However, it was found that the significant decrease in the
      pharmacologically active metabolite M1 following repeated administration of KW
      2449 in primates might hamper the effectiveness of the drug. The mechanism
      underlying this phenomenon was investigated and it was found that the AO activity
      was inhibited in a time-dependent manner in vitro under the co-incubation of KW
      2449 and MAO-B, while neither KW-2449 nor M1 strongly inhibited MAO-B or AO
      activity. These results clearly suggest that MAO-B catalysed iminium ion
      metabolite inhibited AO, prompting us to investigate whether or not the iminium
      ion metabolite covalently binds to endogenous proteins, as has been reported with
      other reactive metabolites as a cause for idiosyncratic toxicity. The association
      of the radioactivity derived from 14 C-KW-2449 with endogenous proteins both in
      vivo and in vitro was confirmed and it was verified that this covalent binding
      was inhibited by the addition of sodium cyanide, an iminium ion-trapping reagent,
      and pargyline, a MAO-B inhibitor. These findings strongly suggest that the
      iminium ion metabolite of KW-2449 is highly reactive in inhibiting AO
      irreversibly and binding to endogenous macromolecules covalently.

PMID- 29451688
TI  - Advancing a field by building consortia: The example of the European LeukemiaNet.

PMID- 29451689
TI  - Barriers to accessing palliative care for pediatric patients with cancer: A
      review of the literature.
AB  - Although many of the 16,000 children in the United States diagnosed who are with
      cancer each year could benefit from pediatric palliative care, these services
      remain underused. Evidence regarding the barriers impeding access to
      comprehensive palliative care is dispersed in the literature, and evidence
      specific to pediatric oncology remains particularly sparse. The purpose of the
      current review was to synthesize the existing literature regarding these barriers
      and the strategies offered to address them. The authors completed a literature
      search using the PubMed, Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), and Web of Science databases. In total, 71 articles were reviewed.
      Barriers to accessing pediatric palliative care were categorized according to the
      4 levels of a modified socioecological model (ie, barriers related to
      policy/payment, health systems, organizations, and individuals). Major themes
      identified at each level included: 1) the lack of consistent and adequate funding
      mechanisms at the policy/payment level, 2) the lack of pediatric palliative care
      programs and workforce at the health systems level, 3) difficulties integrating
      palliative care into existing pediatric oncology care models at the
      organizational level, and 4) the lack of knowledge about pediatric palliative
      care, discomfort with talking about death, and cultural differences between
      providers and patients and their families at the individual level.
      Recommendations to address each of the barriers identified in the literature are
      included. Cancer 2018;124:2278-88. (c) 2018 American Cancer Society.

PMID- 29451690
TI  - Successful therapy for pyoderma gangrenosum with a Janus kinase 2 inhibitor.

PMID- 29451687
TI  - GPCRs in context: sexual dimorphism in the cardiovascular system.
AB  - : Cardiovascular disease (CVD) remains the largest cause of mortality worldwide,
      and there is a clear gender gap in disease occurrence, with men being predisposed
      to earlier onset of CVD, including atherosclerosis and hypertension, relative to
      women. Oestrogen may be a driving factor for female-specific cardioprotection,
      though androgens and sex chromosomes are also likely to contribute to sexual
      dimorphism in the cardiovascular system (CVS). Many GPCR-mediated processes are
      involved in cardiovascular homeostasis, and some exhibit clear sex divergence.
      Here, we focus on the G protein-coupled oestrogen receptor, endothelin receptors
      ETA and ETB and the eicosanoid G protein-coupled receptors (GPCRs), discussing
      the evidence and potential mechanisms leading to gender dimorphic responses in
      the vasculature. The use of animal models and pharmacological tools has been
      essential to understanding the role of these receptors in the CVS and will be key
      to further delineating their sex-specific effects. Ultimately, this may
      illuminate wider sex differences in cardiovascular pathology and physiology.
      LINKED ARTICLES: This article is part of a themed section on Molecular
      Pharmacology of GPCRs. To view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.

PMID- 29451691
TI  - Aquagenic wrinkling of the palms in patients with cystic fibrosis.

PMID- 29451692
TI  - Knee contracture in children with cerebral palsy: association with muscle
      lengths.

PMID- 29451693
TI  - Acute psychosocial stress downregulates N-methyl-d-aspartate receptors in healthy
      human skin.

PMID- 29451694
TI  - Children with facial morphoea managing everyday life: a qualitative study.
AB  - BACKGROUND: Facial morphoea is a chronic inflammatory skin disorder, typically
      presenting in childhood and adolescence, which can be disfiguring, and which has
      been suggested to cause mild-to-moderate impairment in quality of life.
      OBJECTIVES: To explore the everyday experiences of children with facial morphoea
      by examining the psychosocial impact of living with facial morphoea and how
      children and their families manage its impact. METHODS: We used a qualitative,
      social constructionist approach involving focus groups, in-depth interviews and
      drawing activities with 10 children with facial morphoea aged 8-17 years and 13
      parents. Interpretive thematic analysis was utilized to examine the data.
      RESULTS: Children and parents reported on the stress of living with facial
      morphoea, which was related to the lack of knowledge about facial morphoea and
      the extent to which they perceived themselves as different from others. Self
      perceptions were based on the visibility of the lesion, different phases of life
      transitions and the reactions of others (e.g. intrusive questioning and
      bullying). Medication routines, and side-effects such as weight gain, added to
      the stress experienced by the participants. To manage the impact of facial
      morphoea, children and their parents used strategies to normalize the experience
      by hiding physical signs of the illness, constructing explanations about what
      'it' is, and by connecting with their peers. CONCLUSIONS: Understanding what it
      is like to live with facial morphoea from the perspectives of children and
      parents is important for devising ways to help children with the disorder achieve
      a better quality of life. Healthcare providers can help families access resources
      to manage anxiety, deal with bullying and construct adequate explanations of
      facial morphoea, in addition to providing opportunities for peer support.

PMID- 29451695
TI  - Decreased early mortality associated with the treatment of acute myeloid leukemia
      at National Cancer Institute-designated cancer centers in California.
AB  - BACKGROUND: To the authors' knowledge, few population-based studies to date have
      evaluated the association between location of care, complications with induction
      therapy, and early mortality in patients with acute myeloid leukemia (AML).
      METHODS: Using linked data from the California Cancer Registry and Patient
      Discharge Dataset (1999-2014), the authors identified adult (aged >=18 years)
      patients with AML who received inpatient treatment within 30 days of diagnosis. A
      propensity score was created for treatment at a National Cancer Institute
      designated cancer center (NCI-CC). Inverse probability-weighted, multivariable
      logistic regression models were used to determine associations between location
      of care, complications, and early mortality (death <=60 days from diagnosis).
      RESULTS: Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC.
      Patients with AML who were treated at NCI-CCs were more likely to be aged <=65
      years, live in higher socioeconomic status neighborhoods, have fewer
      comorbidities, and have public health insurance. Patients treated at NCI-CCs had
      higher rates of renal failure (23% vs 20%; P = .010) and lower rates of
      respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P =
      .014). After adjustment for baseline characteristics, treatment at an NCI-CC was
      associated with lower early mortality (odds ratio, 0.46; 95% confidence interval,
      0.38-0.57). The impact of complications on early mortality did not differ by
      location of care except for higher early mortality noted among patients with
      respiratory failure treated at non-NCI-CCs. CONCLUSIONS: The initial treatment of
      adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds
      of early mortality compared with treatment at non-NCI-CCs. Lower early mortality
      may result from differences in hospital or provider experience and supportive
      care. Cancer 2018;124:1938-45. (c) 2018 American Cancer Society.

PMID- 29451696
TI  - Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and
      pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell
      lung cancer and an Eastern Cooperative Oncology Group performance status of 2.
AB  - BACKGROUND: The best treatment for patients with advanced non-small cell lung
      cancer (NSCLC) and a poor performance status is not well defined. In this phase 2
      trial, patients were randomized to receive treatment with either single-agent
      pemetrexed or 1 of 2 combination regimens. METHODS: Patients with newly
      diagnosed, histologically confirmed nonsquamous NSCLC and an Eastern Cooperative
      Oncology Group (ECOG) performance status of 2 were stratified by age and serum
      albumin level and were randomized (1:1:1) to 1 of 3 regimens: pemetrexed (arm 1),
      pemetrexed and bevacizumab (arm 2), or pemetrexed, carboplatin, and bevacizumab
      (arm 3). The response to treatment was assessed every 2 cycles; responding and
      stable patients continued treatment until progression or unacceptable toxicity.
      RESULTS: One hundred seventy-two patients were randomized, 162 patients began the
      study treatment, and 146 patients completed 2 cycles and were evaluated for their
      response. The median progression-free survival (PFS) was 2.8 months in arm 1, 4.0
      months in arm 2, and 4.8 months in arm 3. The overall response rates were 15% in
      arm 1, 31% in arm 2, and 44% in arm 3. The overall survival was similar in the 3
      treatment arms. All 3 regimens were relatively well tolerated. Patients receiving
      bevacizumab had an increased incidence of hypertension, proteinuria, and bleeding
      episodes, but most events were mild or moderate. CONCLUSIONS: All 3 regimens were
      feasible for patients with advanced NSCLC and an ECOG performance status of 2.
      The addition of bevacizumab to pemetrexed increased the overall response rate.
      The efficacy of pemetrexed/carboplatin/bevacizumab (median PFS, 4.8 months)
      approached the prespecified study PFS goal of 5 months. Larger studies will be
      necessary to define the role of bevacizumab in addition to standard pemetrexed
      and carboplatin in this population. Cancer 2018;124:1982-91. (c) 2018 American
      Cancer Society.

PMID- 29451697
TI  - Optimizing case reports and case series: guidance on how to improve quality.
AB  - Case reports and case series remain an important part of journals and are often
      first to document medical breakthroughs. This article reviews their
      characteristics, aims and limitations. It provides information on how to increase
      the validity of the bedside decision-making process that these studies report,
      using tools such as validated outcomes and split-body or n-of-1 trials. A section
      describing tools to improve writing of case reports and case series provides
      suggestions for detailed reporting and good evaluation of novelty, validity and
      relevance. It includes general and British Journal of Dermatology-specific
      guidance.

PMID- 29451698
TI  - The ketogenic diet is effective for refractory epilepsy associated with acquired
      structural epileptic encephalopathy.
AB  - AIM: Ketogenic diet therapies have proven efficacy for refractory epilepsy. There
      are many reports of their use in the genetic developmental and epileptic
      encephalopathies; however, little attention has been paid as to whether the diet
      is also effective in individuals with an acquired structural aetiology. We
      observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic
      encephalopathy. We then analysed our cases with refractory structural epilepsies
      of acquired origin to characterize their response to the ketogenic diet. METHOD:
      The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1.
      Seizure frequency at 1 month, 3 months, 6 months, 1 year, and 2 years was
      ascertained. A responder was defined as greater than 50% seizure reduction
      compared to baseline. RESULTS: Seven of the nine patients were responders at 3
      months. INTERPRETATION: Somewhat surprisingly we found that the ketogenic diet
      was effective in patients with a developmental and epileptic encephalopathy due
      to an acquired structural aetiology. This cohort may not be routinely considered
      for the ketogenic diet because of their structural and acquired, rather than
      genetic, basis. The ketogenic diet should be considered early in the management
      of patients with acquired structural encephalopathies as it can improve seizure
      control with the potential to improve developmental outcome. WHAT THIS PAPER
      ADDS: The ketogenic diet was effective in children with epilepsy associated with
      an acquired structural aetiology.

PMID- 29451699
TI  - Development and validation of the Pediatric Stroke Quality of Life Measure.
AB  - AIM: To develop and validate a disease-specific parent proxy and child quality of
      life (QoL) measure for patients aged 2 to 18 years surviving cerebral sinovenous
      thrombosis (CSVT) and arterial ischaemic stroke (AIS). METHOD: Utilizing
      qualitative and quantitative methods, we developed a 75-item Pediatric Stroke
      Quality of Life Measure (PSQLM) questionnaire. We mailed the PSQLM and a
      standardized generic QoL measure, Pediatric Quality of Life Inventory (PedsQL),
      to 353 families. Stroke type, age at stroke, and neurological outcome on the
      Pediatric Stroke Outcome Measure were documented. We calculated the internal
      consistency, validity, and reliability of the PSQLM. RESULTS: The response rate
      was 29%, yielding a sample of 101 patients (mean age 9y 9mo [SD 4.30]; 69 AIS
      [68.3%], 32 CSVT [31.7%]). The internal consistency of the PSQLM was high
      (Cronbach's alpha=0.94-0.97). Construct validity for the PSQLM was moderately
      strong (r=0.3-0.4; p<0.003) and, as expected, correlation with the PedsQL was
      moderate, suggesting the PSQLM operationalizes QoL distinct from the PedsQL. Test
      retest reliability at 2 weeks was very good (intraclass correlation coefficient
      [ICC] 0.85-0.95; 95% confidence interval 0.83-0.97) and good agreement was
      established between parent and child report (ICC 0.63-0.76). INTERPRETATION: The
      PSQLM demonstrates sound psychometric properties. Further research will seek to
      increase its clinical utility by reducing length and establishing responsiveness
      for descriptive and longitudinal evaluative assessment. WHAT THIS PAPER ADDS: A
      pediatric stroke-specific quality of life (QoL) measurement tool for assessments
      based on perceptions of importance and satisfaction. Moderate-to-high reliability
      and validity established for a new clinical scale evaluating QoL among children
      with stroke. Perceived QoL measured using the Pediatric Stroke Quality of Life
      Measure appears lower in children with neurological impairment.

PMID- 29451700
TI  - Dermatology training across the globe, part II: a summary of the literature.

PMID- 29451701
TI  - Phase 1b study of pasireotide, everolimus, and selective internal
      radioembolization therapy for unresectable neuroendocrine tumors with hepatic
      metastases.
AB  - BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and
      selective internal radioembolization (SIRT) are approved treatments. Pasireotide
      is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3,
      and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and
      inhibit rebound angiogenesis. This study evaluated the safety of pasireotide,
      everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels
      of everolimus (2.5, 5, and 10 mg/day), pasireotide (600 MUg twice daily), and
      SIRT (SIR-Spheres dose on days 9 and 37). Eligibility criteria included well or
      moderately differentiated NETs, bilobar liver metastases, and progression on long
      acting octreotide. Toxicities and responses were evaluated with the Common
      Terminology Criteria for Adverse Events and the Response Evaluation Criteria in
      Solid Tumors (version 1.1). Dose-limiting toxicities (DLTs) were defined in the
      first 28 days. Correlative markers-angiopoietin 1, angiopoietin 2, basic
      fibroblast growth factor, collagen V, insulin-like growth factor binding protein
      1, insulin-like growth factor binding protein 1, interleukin 8, M30, M65,
      placenta growth factor, and vascular endothelial growth factor receptor 2-were
      assessed. The Norfolk Quality of Life-Neuroendocrine Tumor Questionnaire was used
      to assess the quality of life (QOL). RESULTS: Thirteen patients were enrolled; 1
      was not evaluable for the primary endpoint. Eleven patients had well
      differentiated tumors. The primary sites included small bowel (4), pancreas (3),
      lung (2), colon (1), gastric (1), and unknown primary (2) were unknown. Four had
      liver-only disease; 12 completed the planned treatment. No DLTs were observed.
      There was no treatment-related mortality. The most common toxicity was
      hyperglycemia. Clinically significant liver toxicity was not observed. One
      patient had liver progression. QOL improved on treatment. The median progression
      free survival and overall survival were 18.6 and 46.3 months, respectively.
      CONCLUSIONS: The recommended phase 2 dose of everolimus is 10 mg daily in
      combination with pasireotide and SIRT. The regimen is well tolerated. Preliminary
      activity appears promising. Cancer 2018;124:1992-2000. (c) 2018 American Cancer
      Society.

PMID- 29451702
TI  - Severity of cerebral palsy and likelihood of adverse events after botulinum toxin
      A injections.
AB  - AIM: To determine the incidence of common adverse events after botulinum toxin A
      (BoNT-A) injections in children with cerebral palsy (CP) and to identify whether
      the severity of CP influences the incidence of adverse events. METHOD: This was
      an observational study of patients attending a BoNT-A clinic at a tertiary
      paediatric hospital (2010-2014). Data examined included procedural adverse events
      at the time of injection and at follow-up. Systemic adverse events were defined
      as lower respiratory tract illnesses, generalized weakness, dysphagia, and death.
      Severity of CP was categorized by the Gross Motor Function Classification System
      (GMFCS). The relationships between GMFCS and adverse events were analysed using
      negative binomial regression models. RESULTS: In total, 591 children underwent
      2219 injection episodes. Adverse events were reported during the procedure (130
      [6%] injection episodes) and at follow-up (492 [22%] injection episodes). There
      were significantly increased rates of systemic adverse events in injection
      episodes involving children in GMFCS level IV (incidence rate ratio [IRR] 3.92
      [95% confidence interval] 1.45-10.57]) and GMFCS level V (IRR 7.37 [95%
      confidence interval 2.90-18.73]; p<0.001). INTERPRETATION: Adverse events after
      BoNT-A injections are common but mostly mild and self-limiting. Children in GMFCS
      levels IV and V are at increased risk of systemic adverse events. The
      relationship between CP severity and BoNT-A adverse events is complex and further
      research is required to better understand this relationship. WHAT THIS PAPER
      ADDS: Adverse events reported at the time of botulinum toxin A injection occurred
      in 6% of injection episodes. Adverse events were reported at follow-up in 22% of
      injection episodes. Children in Gross Motor Function Classification System
      (GMFCS) levels IV and V have increased rates of systemic adverse events. Children
      in GMFCS levels IV and V report less local weakness and pain.

PMID- 29451703
TI  - Mechanisms of imidazoline I2 receptor agonist-induced antinociception in rats:
      involvement of monoaminergic neurotransmission.
AB  - BACKGROUND AND PURPOSE: Although the antinociceptive efficacies of imidazoline I2
      receptor agonists have been established, the exact post-receptor mechanisms
      remain unknown. This study tested the hypothesis that monoaminergic transmission
      is critical for I2 receptor agonist-induced antinociception. EXPERIMENTAL
      APPROACH: von Frey filaments were used to assess antinociceptive effects of two
      I2 receptor agonists, 2-BFI and CR4056 on chronic constriction injury (CCI)
      induced neuropathic pain or complete Freund's adjuvant (CFA)-induced inflammatory
      pain in rats. Rectal temperature was measured to assess hypothermic effects of 2
      BFI. A two-lever drug discrimination paradigm in which rats were trained to
      discriminate 5.6 mg.kg-1 2-BFI (i.p.) from its vehicle was used to examine the
      discriminative stimulus effects of 2-BFI. In each experiment, pharmacological
      mechanisms were investigated by combining 2-BFI or CR4056 with various
      pharmacological manipulations of the monoaminergic system including selective
      reuptake inhibition, monoamine depletion and monoamine receptor antagonism. KEY
      RESULTS: In the CCI model, selective reuptake inhibitors of 5-HT (fluoxetine) or
      noradrenaline (desipramine), but not dopamine (GBR12909), enhanced 2-BFI-induced
      antinociception. Selective depletion of 5-HT or noradrenaline almost abolished 2
      BFI-induced antinociception. 5-HT1A , 5-HT2A and alpha1 -adrenoceptor
      antagonists, but not other monoaminergic antagonists, attenuated 2-BFI and CR4056
      induced antinociception in CCI and/or CFA models. However, none of these
      monoamine receptor antagonists significantly altered 2-BFI-induced hypothermia or
      discriminative stimulus effects. CONCLUSIONS AND IMPLICATIONS: Antinociception
      induced by I2 receptor agonists was mediated by serotonergic and noradrenergic
      mechanisms with 5-HT1A , 5-HT2A and alpha1 -adrenoceptor being particularly
      important. In contrast, the hypothermic and discriminative stimulus effects of I2
      receptor agonists were mediated by distinct, independent mechanisms.

PMID- 29451704
TI  - MAIT cells and microbial immunity.
AB  - Mucosal-associated invariant T (MAIT) cells, the most abundant T-cell subset in
      humans, are increasingly being recognized for their importance in microbial
      immunity. MAIT cells accumulate in almost every mucosal tissue examined,
      including the lung, liver and intestinal tract, where they can be activated
      through T-cell receptor (TCR) triggering as well as cytokine stimulation in
      response to a host of microbial products. In this review, we specifically discuss
      MAIT cell responses to bacterial and fungal infections, with a focus on responses
      that are both MR1-dependent and -independent, the evidence for diversity in MAIT
      TCR usage in response to discrete microbial products, protective immunity induced
      by MAIT cells, and MAIT cell antimicrobial functions in the context of these
      infections.

PMID- 29451706
TI  - The co-formulation of insulin degludec and insulin aspart lowers fasting plasma
      glucose and rates of confirmed and nocturnal hypoglycaemia, independent of
      baseline glycated haemoglobin levels, disease duration or body mass index: A
      pooled meta-analysis of phase III studies in patients with type 2 diabetes.
AB  - AIMS: To investigate whether the proven benefits of insulin degludec (IDeg)
      combined with insulin aspart (IAsp), known as IDegAsp, given twice daily, extend
      across a wide spectrum of patients with diabetes. MATERIALS AND METHODS: This was
      a post hoc pooled analysis of 5 phase III randomized, 26-week, open-label, treat
      to-target trials comparing IDegAsp twice daily (n = 1111) with one of two
      comparators: premixed insulin (biphasic insulin aspart 30 [BIAsp 30]) twice daily
      (n = 561) or IDeg once daily + IAsp (n = 136). Patient data were stratified
      according to baseline glycated haemoglobin (HbA1c) or fasting plasma glucose
      (FPG) categories, as well as by baseline duration of diabetes or body mass index
      (BMI) categories. RESULTS: We conducted a meta-analysis of 5 clinical trials:
      NCT01513590, NCT01009580, NCT01059812, NCT01680341 and NCT01713530. End-of-trial
      results were broadly consistent, with differences between IDegAsp and comparators
      observed in phase III trials. HbA1c results were similar for IDegAsp and the
      comparators in all baseline characteristic (HbA1c, duration of diabetes or BMI)
      and category groups (number ranges). Significantly lower FPG level was observed
      with IDegAsp vs comparators in all baseline characteristic and most category
      groups (excluding FPG <5.5 mmol/L). Significantly lower insulin doses were
      observed with IDegAsp vs comparators in all baseline characteristic and half of
      the category groups, and significantly lower rates of confirmed and nocturnal
      confirmed hypoglycaemia were observed with IDegAsp vs comparators in all baseline
      variable and category groups. CONCLUSIONS: IDegAsp retains a consistent safety
      and efficacy profile in patients with different baseline characteristics.

PMID- 29451707
TI  - Simultaneous Preparation and Comparison of the Osteogenic Effects of Epimedins A 
      C and Icariin from Epimedium brevicornu.
AB  - In this study, epimedins A-, B-, and C-, and icariin-rich extracts were
      simultaneously isolated from Epimedium brevicornu Maxim. through a convenient
      four-stage process consisting of solvent extraction, macroporous resin column pre
      concentration, extraction fractionation, and reversed-phase (RP) silica gel
      column chromatography. Single factor experiments and response surface methodology
      (RSM) were used to optimize the preparation conditions. In the final products,
      the purities of epimedins A - C and icariin were 23.04%, 64.50%, 54.92%, and
      77.54%, respectively, which will lay a foundation for the further purification of
      epimedin monomers and full utilization of Epimedium resources. Meanwhile, the
      osteogenic effects of epimedins A - C were investigated for the first time and
      compared with that of icariin, which will provide guidance for the clinical
      applications of Epimedium in the treatment of osteoporosis.

PMID- 29451705
TI  - Modeling asthma: Pitfalls, promises, and the road ahead.
AB  - Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the
      lower airways, with exacerbations that feature airway inflammation and bronchial
      hyperresponsiveness. Asthma has been modeled extensively via disease induction in
      both wild-type and genetically manipulated laboratory mice (Mus musculus).
      Antigen sensitization and challenge strategies have reproduced numerous important
      features of airway inflammation characteristic of human asthma, notably the
      critical roles of type 2 T helper cell cytokines. Recent models of disease
      induction have advanced to include physiologic aeroallergens with prolonged
      respiratory challenge without systemic sensitization; others incorporate tobacco,
      respiratory viruses, or bacteria as exacerbants. Nonetheless, differences in lung
      size, structure, and physiologic responses limit the degree to which airway
      dynamics measured in mice can be compared to human subjects. Other rodent
      allergic airways models, including those featuring the guinea pig (Cavia
      porcellus) might be considered for lung function studies. Finally, domestic cats
      (Feline catus) and horses (Equus caballus) develop spontaneous obstructive airway
      disorders with clinical and pathologic features that parallel human asthma.
      Information on pathogenesis and treatment of these disorders is an important
      resource.

PMID- 29451708
TI  - Promotion of bone regeneration on titanium implants through a chemical treatment
      process using calcium phosphate slurry: Microscopic analysis, cellular response,
      and animal experiment.
AB  - The present study provides scientific evidence that a new chemical treatment
      process using calcium phosphate slurry promotes bone regeneration on titanium
      (Ti) implants. The material's surface modified by the treatment was analyzed
      using microscopic observation and the bone regeneration efficacy was evaluated
      both in vitro and in vivo. Formation of a thin hydroxyapatite layer with a
      thickness of about 50 nm and an increase of surface roughness were confirmed by
      microscopic observations. Histological evaluation of rat femora implanted with
      the specimens showed that the areas of the specimens directly attached to bone
      tissue were significantly more extensive than those implanted with control Ti at
      2 and 8 weeks. Likewise, on the treated Ti, ALP activity, osteopontin,
      osteocalcin, and calcium contents of rat bone marrow stromal cells were
      significantly higher than on the control Ti. Furthermore, reverse transcription
      polymerase chain reaction showed greater expression of messenger ribonucleic acid
      encoding Cbfa1 and collagen type1 on the treated Ti at 2 weeks. Based on these
      results, we concluded that the new process was effective to enhance the
      osteoconductivity of Ti. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part
      B: Appl Biomater, 106B: 2716-2724, 2018.

PMID- 29451709
TI  - Shortcomings in the management of undescended testis: guideline intention vs
      reality and the underlying causes - insights from the biggest German cohort.
AB  - OBJECTIVES: To assess the implementation of the current guideline and identify
      potential underlying causes for late surgery in children with undescended testis
      (UDT) in Germany. UDT is the most common surgical issue in paediatric urology and
      to avoid malignant degeneration and subfertility current guidelines recommend
      orchidopexy during the first year of life; however, this seems not to be
      implemented in practice. PATIENTS AND METHODS: In all, 5 547 patients with
      cryptorchidism at 16 hospitals nationwide were studied regarding age at
      orchidopexy between 2003 and 2016. Multivariate analysis was performed to
      identify factors influencing timing of surgery. Additionally, a survey on
      knowledge of UDT management was conducted amongst physicians treating boys and
      final-year medical students. RESULTS: Between 2003 and 2008 only 4% of boys with
      UDT underwent surgery before the age of 1 year. After the guideline update from
      2009, this figure was 5% from 2010 to 2012, and 8% from 2013 to 2016. The
      presence of a specialised department for paediatric surgery, as well as a high
      UDT case-to-year ratio positively influenced the timing of orchidopexy. The
      survey revealed discipline-specific differences in the levels of knowledge about
      UDT management. One-third of respondents did not know the guideline
      recommendations and 61% felt insufficiently informed. International comparisons
      revealed significant differences in the age at surgery of boys with UDT, with
      Germany and Great Britain ranging in the middle of the field. CONCLUSIONS:
      Currently, only a small proportion of boys with UDT are operated upon during
      their first year of life. The level of knowledge in attending physicians remains
      in need of improvement. This should be actively addressed, i.e. by campaigns and
      educational programmes. Further studies are needed to investigate the underlying
      causes of late orchidopexy in UDT.

PMID- 29451711
TI  - Fundamental Differences in Burst Stimulation Waveform Design: Eliminating
      Confusion in the Marketplace.

PMID- 29451712
TI  - Lipid-Modifying Effects of Chitosan Supplementation in Humans: A Pooled Analysis
      with Trial Sequential Analysis.
AB  - SCOPE: We performed a pooled analysis with trial sequential analysis (TSA) to
      evaluate the efficacy and safety of chitosan supplementation on serum lipids in
      humans. METHODS AND RESULTS: Medline, EMBASE, and CENTRAL databases were queried.
      Impact was expressed as a weighted mean difference (WMD) and 95% confidence
      interval (CI). Sensitivity analysis was conducted using the leave-one-out method.
      Statistical heterogeneity, publication bias, TSA, and subgroup analyses were also
      assessed. Fourteen trials (21 treatment arms) encompassing 1108 participants were
      suitable for statistical pooling. Chitosan supplementation significantly improved
      the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C)
      concentrations in all patients. The WMDs were -0.20 mmol L-1 (95% CI, -0.35 to 
      0.05; p = 0.009) for TC, and -0.20 mol L-1 (95% CI, -0.26 to -0.15; p = 0.0001)
      for LDL-C, respectively. TSA demonstrated that the cumulative Z-curve crossed the
      trial sequential monitoring boundary for benefit providing conclusive evidence
      for the benefit of chitosan. However, no significant changes were seen with high
      density lipoprotein cholesterol (HDL-C) and triglycerides. Our findings were
      robust after sensitivity analyses, and no serious adverse events were reported
      with chitosan intake. CONCLUSION: Supplementation with chitosan effectively
      reduces plasma concentrations of TC and LDL-C. Current evidence indicates daily
      chitosan supplementation as a candidate for therapeutic lipid management
      strategies.

PMID- 29451710
TI  - Salvisertin A, a New Hexacyclic Triterpenoid, and Other Bioactive Terpenes from
      Salvia deserta Root.
AB  - Using various chromatographic methods, a new hexacyclic triterpenoid,
      2beta,3beta,24beta-trihydroxy-12,13-cyclotaraxer-l4-en-28oic acid (1), together
      with ten known compounds, 2alpha,3alpha,23-trihydroxyurs-12,20(30)-dien-28oic
      acid (2), 6,7-dehydroroyleanone (3), horminone (4), 7-O-methylhorminone (5),
      sugiol (6), demethylcryptojaponol (7), 14-deoxycoleon U (8), 5,6-didehydro-7
      hydroxy-taxodone (9), ferruginol (10), and dichroanone (11), were isolated from
      the roots of Salvia deserta. Their structures were identified on the basis of
      spectroscopic analysis and comparison with the reported data. The individual
      compounds (1, 3 - 8) were screened for cytotoxic activity, using the
      sulforhodamine B bioassay (SRB) method. As the results, Compounds 3, 5, and 8
      showed cytotoxic potency against A549, MDA-MB-231, KB, KB-VIN, and MCF7 cell
      lines with IC50 values ranging from 6.5 to 10.2 MUm.

PMID- 29451713
TI  - Glucose effectiveness is a critical pathogenic factor leading to glucose
      intolerance and type 2 diabetes: An ignored hypothesis.
AB  - BACKGROUND: Although the ability of glucose to mediate its own in vivo metabolism
      is long documented, the quantitative measurement of whole body glucose-mediated
      glucose disposal at basal insulin levels (glucose effectiveness [GE]), followed
      the introduction of the Minimal Model intravenous glucose tolerance test
      technique. METHODS: A literature review, combined with our own studies, of the
      role of GE in glucose metabolism in normal and "at risk" individuals, was
      undertaken to determine GE's contribution to glucose homeostasis. RESULTS: GE
      accounts for ~45% to 65% of glucose disposal in man. A negative association
      between GE and insulin meditated glucose disposal (Si), is present in normal
      subjects without a family history of type 2 diabetes mellitus but is absent in
      normoglycaemic "at risk" relatives with a positive family history of diabetes
      mellitus. Intracellular GE disposal is mediated by mass action of glucose through
      the skeletal muscle membrane via facilitated Glut 4 transporters. However, GE is
      frequently forgotten as a significant contributor to the development of glucose
      intolerance in "at risk" individuals. Only limited studies have examined the role
      of a lower GE in such normoglycemic subjects with preexisting mild insulin
      resistance and beta-cell dysfunction. These studies demonstrate that in "at risk"
      individuals, an initial low GE is a key contributor and predictor of future
      glucose intolerance, whereas an initial raised GE is protective against future
      glucose intolerance. CONCLUSION: In "at risk" individuals, a low GE and
      genetically determined vulnerable beta-cell function are more critical
      determinants of future glucose intolerance than their preexisting insulin
      resistant state.

PMID- 29451714
TI  - Development of regenerative and flexible fibroin-based wound dressings.
AB  - Skin injuries represent a health problem with consequences in terms of morbidity,
      disability and life quality. Numerous strategies have been developed for the
      treatment of wounds, including skin substitutes, biomembranes, scaffolds, and
      smart dressings. The excellent properties of fibroin can be exploited for the
      development of advanced wound dressing biomaterials, aiming at promoting the
      wound healing process. In this work, silk fibroin films modified through the
      addition of glucose were developed to enhance flexibility of medical device
      without affecting the biocompatibility, to promote wound healing and to improve
      the patient well-being. The glucose/fibroin blend was characterized through
      Fourier transform infrared spectroscopy and differential scanning calorimetry to
      analyze the protein structure. Absorption capacity, mechanical properties,
      wettability and bacterial biofilm formation on silk fibroin films were also
      analyzed to study the effect of the addition of a plasticizer on the properties
      of the wound dressing. The stability of the films was analyzed through in vitro
      biodegradability tests. The biocompatibility and regenerative properties were
      demonstrated through appropriate cellular assays. The results demonstrated that
      the addition of glucose induced crystallization and provided good flexibility and
      absorption capacity of silk fibroin films. Glucose modified silk fibroin films
      were biocompatible and had a positive effect in promoting the wound closure. (c)
      2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29451716
TI  - Improving Growth for Infants <=1250 Grams Receiving an Exclusive Human Milk Diet.
AB  - BACKGROUND: An exclusive human milk diet (EHM) fortified with human milk-based
      fortifier decreases necrotizing enterocolitis (NEC) compared to maternal milk
      supplemented with preterm formula and bovine fortifier (PTF). Growth has been
      less with EHM and also maternal milk supplemented with donor human milk and
      bovine fortifier (HMBF). The objective was to evaluate the effect of a
      standardized feeding protocol on the growth of infants <=1250 g birth weight
      supported with EHM and HMBF. The effect on the incidence of NEC was also
      evaluated. DESIGN/METHODS: A retrospective study of growth before and after
      implementation of a feeding protocol for infants who received either EHM or HMBF.
      Primary outcomes were weight, length, and head circumference gain velocities from
      birth to discharge. The incidence of NEC was also recorded. RESULTS: Analysis of
      covariance for 379 total infants showed that earlier day of life for
      fortification to 24 Kcal/oz was associated with increased weight gain (p =
      0.0166) and length gain (p = 0.0064). Implementation of the feeding protocol was
      associated with increased head circumference gain (p = 0.006). EHM was associated
      with decreased incidence of NEC (p = 0.0302). CONCLUSIONS: Implementation of a
      standardized feeding protocol including earlier fortification of maternal milk
      was associated with improved growth for infants receiving human milk feedings.
      EHM significantly decreased NEC. Earlier fortification had no effect on NEC.

PMID- 29451715
TI  - Transitions in sex determination and sex chromosomes across vertebrate species.
AB  - Despite the prevalence of sexual reproduction across eukaryotes, there is a
      remarkable diversity of sex-determination mechanisms. The underlying causes of
      this diversity remain unclear, and it is unknown whether there are convergent
      trends in the directionality of turnover in sex-determination mechanisms. We used
      the recently assembled Tree of Sex database to assess patterns in the evolution
      of sex-determination systems in the remarkably diverse vertebrate clades of
      teleost fish, squamate reptiles and amphibians. Contrary to theoretical
      predictions, we find no evidence that the evolution of separate sexes is
      irreversible, as transitions from separate sexes to hermaphroditism occur at
      higher rates than the reverse in fish. We also find that transitions from
      environmental sex determination to genetic sex determination occur at higher
      rates than the reverse in both squamates and fish, suggesting that genetic sex
      determination is more stable. However, our data are not consistent with the
      hypothesis that heteromorphic sex chromosomes are an "evolutionary trap." Rather,
      we find similar transition rates between homomorphic and heteromorphic sex
      chromosomes in both fish and amphibians, and to environmental sex determination
      from heteromorphic vs. homomorphic sex chromosome systems in fish. Finally, we
      find that transitions between male and female heterogamety occur at similar rates
      in amphibians and squamates, while transitions to male heterogamety occur at
      higher rates in fish. Together, these results provide the most comprehensive view
      to date of the evolution of vertebrate sex determination in a phylogenetic
      context, providing new insight into long-standing questions about the evolution
      of sexual reproduction.

PMID- 29451717
TI  - Modeling of cytometry data in logarithmic space: When is a bimodal distribution
      not bimodal?
AB  - Recent efforts in systems immunology lead researchers to build quantitative
      models of cell activation and differentiation. One goal is to account for the
      distributions of proteins from single-cell measurements by flow cytometry or mass
      cytometry as readout of biological regulation. In that context, large cell-to
      cell variability is often observed in biological quantities. We show here that
      these readouts, viewed in logarithmic scale may result in two easily
      distinguishable modes, while the underlying distribution (in linear scale) is
      unimodal. We introduce a simple mathematical test to highlight this mismatch. We
      then dissect the flow of influence of cell-to-cell variability proposing a
      graphical model which motivates higher-dimensional analysis of the data. Finally
      we show how acquiring additional biological information can be used to reduce
      uncertainty introduced by cell-to-cell variability, helping to clarify whether
      the data is uni- or bimodal. This communication has cautionary implications for
      manual and automatic gating strategies, as well as clustering and modeling of
      single-cell measurements. (c) 2018 International Society for Advancement of
      Cytometry.

PMID- 29451719
TI  - Primary sebocytes and sebaceous gland cell lines for studying sebaceous
      lipogenesis and sebaceous gland diseases.
AB  - Sebocytes, the major cell type in sebaceous glands, are differentiated epithelial
      cells that gradually accumulate lipids and eventually disrupt, releasing their
      content (sebum) in a secretory process known as holocrine secretion. Via the hair
      canal, sebum reaches the skin surface, where it has several known or postulated
      functions, including pheromonal, thermoregulatory, antimicrobial and antioxidant
      activities. Altered sebum secretion and/or structural sebaceous gland changes
      have also been involved in the pathogenesis of skin diseases, such as acne
      vulgaris and some forms of alopecia. Here, we assess how recent work employing
      primary sebocytes and sebaceous gland cell lines contributed for our
      understanding of sebaceous lipogenesis and its role in skin health and disease.

PMID- 29451718
TI  - KIAA0247 inhibits growth, migration, invasion of non-small-cell lung cancer
      through regulating the Notch pathway.
AB  - Lung cancer remains the leading cause of cancer-related death worldwide. Previous
      studies have shown that the novel KIAA0247 gene potentially targeted by the tumor
      suppressor p53 may inhibit the development of several cancers. However, the exact
      function of KIAA0247 in non-small-cell lung cancer (NSCLC) is unknown. The
      purpose of the present study was to clarify the role of KIAA0247 in NSCLC.
      KIAA0247 expression was evaluated in tumors and adjacent normal tissues of 197
      NSCLC patients by immunohistochemistry and real-time PCR and analyzed for
      association with clinicopathological parameters. Results indicated that KIAA0247
      levels positively correlated with cell differentiation (P < .001) and patient
      survival (P < .0001) and negatively correlated with lymph node metastasis (P <
      .001) and advanced p-TNM stage (P < .001). In cultured NSCLC cell lines, KIAA0247
      overexpression inhibited cell migration, invasion, and proliferation and
      downregulated the expression of Jagged1, Notch1 intracellular domain (NICD),
      Snail, cyclin D1, RhoA, RhoC, and MMP9, while upregulating that of E-cadherin and
      p21. The Notch inhibitor DAPT reduced the biological effects of KIAA0247
      knockdown, suggesting that KIAA0247 decreased the carcinogenic activity of NSCLC
      cells through downregulation of Notch signaling. Our results indicate that
      KIAA0247 inhibits NSCLC progression by reducing the metastatic potential of
      cancer cells through downregulation of the Notch pathway, which may underlie the
      association of KIAA0247 expression with favorable clinicopathological
      characteristics of NSCLC patients. These findings suggest that KIAA0247 is a
      candidate prognostic biomarker and potential therapeutic target in NSCLC.

PMID- 29451720
TI  - Detection of membrane protein-protein interaction in planta based on dual-intein
      coupled tripartite split-GFP association.
AB  - Despite the great interest in identifying protein-protein interactions (PPIs) in
      biological systems, only a few attempts have been made at large-scale PPI
      screening in planta. Unlike biochemical assays, bimolecular fluorescence
      complementation allows visualization of transient and weak PPIs in vivo at
      subcellular resolution. However, when the non-fluorescent fragments are highly
      expressed, spontaneous and irreversible self-assembly of the split halves can
      easily generate false positives. The recently developed tripartite split-GFP
      system was shown to be a reliable PPI reporter in mammalian and yeast cells. In
      this study, we adapted this methodology, in combination with the beta-estradiol
      inducible expression cassette, for the detection of membrane PPIs in planta.
      Using a transient expression assay by agroinfiltration of Nicotiana benthamiana
      leaves, we demonstrate the utility of the tripartite split-GFP association in
      plant cells and affirm that the tripartite split-GFP system yields no spurious
      background signal even with abundant fusion proteins readily accessible to the
      compartments of interaction. By validating a few of the Arabidopsis PPIs,
      including the membrane PPIs implicated in phosphate homeostasis, we proved the
      fidelity of this assay for detection of PPIs in various cellular compartments in
      planta. Moreover, the technique combining the tripartite split-GFP association
      and dual-intein-mediated cleavage of polyprotein precursor is feasible in stably
      transformed Arabidopsis plants. Our results provide a proof-of-concept
      implementation of the tripartite split-GFP system as a potential tool for
      membrane PPI screens in planta.

PMID- 29451721
TI  - Sodium-glucose co-transporter-2 inhibitors as add-on therapy to insulin for type
      1 diabetes mellitus: Systematic review and meta-analysis of randomized controlled
      trials.
AB  - New treatments for type 1 diabetes are an unmet need. We investigated the
      efficacy and safety of adding sodium-glucose co-transporter-2 (SGLT2) inhibitors
      to insulin for type 1 diabetes by conducting a meta-analysis of prospective
      randomized, placebo-controlled trials. A search of electronic databases up to
      October 2017 identified 1361 studies, of which 14 were investigated (N = 4591).
      Meta-analysis showed that SGLT2 inhibitor therapy significantly reduced glycated
      haemoglobin (HbA1c) concentration by 0.4% (95% confidence interval [CI] 0.35,
      0.46; P < .001, I2 = 0%), fasting plasma glucose by 1.14 mmol/L (95% CI
      0.8,1.47), body weight by 2.68 kg (95% CI 2.0, 3.36), and systolic blood pressure
      by 3.37 mmHg (95% CI 1.46, 5.28). In addition, bolus insulin decreased by 3.6
      units/day (95% CI 2.0, 5.3), and basal insulin decreased by 4.2 units/day (95% CI
      2.2, 6.3). Continuous glucose monitoring showed a decrease in glucose excursions
      compared with placebo, with reduced variation of mean blood glucose, glucose
      standard deviation, and mean amplitude of glucose excursion. There was no
      significant increase in the rate of hypoglycaemia or severe hypoglycaemia;
      however, SGLT2 inhibitor therapy increased diabetic ketoacidosis (odds ratio [OR]
      3.38) and genital tract infection (OR 3.44). Add-on SGLT2 inhibitor therapy might
      be advantageous for type 1 diabetes, but its use should be considered carefully.

PMID- 29451722
TI  - Enhanced Photodynamic Therapy by Reduced Levels of Intracellular Glutathione
      Obtained By Employing a Nano-MOF with CuII as the Active Center.
AB  - In photodynamic therapy (PDT), the level of reactive oxygen species (ROS)
      produced in the cell directly determines the therapeutic effect. Improvement in
      ROS concentration can be realized by reducing the glutathione (GSH) level or
      increasing the amount of photosensitizer. However, excessive amounts
      photosensitizer may cause side effects. Therefore, the development of
      photosensitizers that reduce GSH levels through synergistically improving ROS
      concentration in order to strengthen the efficacy of PDT for tumor is important.
      We report a nano-metal-organic framework (CuII -metalated nano-MOF {CuL-[AlOH]2
      }n (MOF-2, H6 L=mesotetrakis(4-carboxylphenyl)porphyrin)) based on CuII as the
      active center for PDT. This MOF-2 is readily taken up by breast cancer cells, and
      high levels of ROS are generated under light irradiation. Meanwhile,
      intracellular GSH is considerably decreased owing to absorption on MOF-2; this
      synergistically increases ROS concentration and accelerates apoptosis, thereby
      enhancing the effect of PDT. Notably, based on the direct adsorption of GSH, MOF
      2 showed a comparable effect with the commercial antitumor drug camptothecin in a
      mouse breast cancer model. This work provides strong evidence for MOF-2 as a
      promising new PDT candidate and anticancer drug.

PMID- 29451723
TI  - Clickable Polyamine Derivatives as Chemical Probes for the Polyamine Transport
      System.
AB  - Polyamines are essential for cell growth and differentiation, but their
      trafficking by the polyamine transport system is not fully understood. Herein,
      the synthesis of several azido-derivatized polyamines for easy conjugation by
      click chemistry is described. Attachment of a 4,4-difluoro-4-bora-3a,4a-diaza-s
      indacene (BODIPY) dye gave fluorescent polyamine probes, which were tested in
      cell culture. The linear probe series showed superior cellular uptake compared
      with that of probes in which the dye was attached to a branch on one of the
      central amines. Interestingly, the linear probes accumulated rapidly in cancer
      cells (MCF-7), but not in nontumorigenic cells (MCF-10A). The fluorescent
      polyamine probes are therefore applicable to the study of polyamine trafficking,
      whereas the azido polyamines may be further utilized to transport cargo into
      cancer cells by exploiting the polyamine transport system.

PMID- 29451724
TI  - Palladium-Catalyzed Decarboxylative Heck-Type Coupling of Activated Aliphatic
      Carboxylic Acids Enabled by Visible Light.
AB  - The palladium-catalyzed coupling reaction of N-hydroxyphthalimide esters and
      styrenes to deliver exclusively (E)-substituted olefins under irradiation with
      visible light is reported. This method tolerates N-hydroxyphthalimide esters
      derived from primary, secondary, tertiary as well as benzylic carboxylic acids.
      Notably, Pd(PPh3 )4 is employed as an inexpensive palladium source and no
      addition of base or classical photocatalyst is required. Mechanistic studies
      suggest a light-mediated single-electron reduction of the activated acid by a
      photoexcited palladium(0) species to access alkyl radicals through
      decarboxylation.

PMID- 29451726
TI  - Single organelle dynamics linked to 3D structure by correlative live-cell imaging
      and 3D electron microscopy.
AB  - Live-cell correlative light-electron microscopy (live-cell-CLEM) integrates live
      movies with the corresponding electron microscopy (EM) image, but a major
      challenge is to relate the dynamic characteristics of single organelles to their
      3-dimensional (3D) ultrastructure. Here, we introduce focused ion beam scanning
      electron microscopy (FIB-SEM) in a modular live-cell-CLEM pipeline for a single
      organelle CLEM. We transfected cells with lysosomal-associated membrane protein 1
      green fluorescent protein (LAMP-1-GFP), analyzed the dynamics of individual GFP
      positive spots, and correlated these to their corresponding fine-architecture and
      immediate cellular environment. By FIB-SEM we quantitatively assessed
      morphological characteristics, like number of intraluminal vesicles and contact
      sites with endoplasmic reticulum and mitochondria. Hence, we present a novel way
      to integrate multiple parameters of subcellular dynamics and architecture onto a
      single organelle, which is relevant to address biological questions related to
      membrane trafficking, organelle biogenesis and positioning. Furthermore, by using
      CLEM to select regions of interest, our method allows for targeted FIB-SEM, which
      significantly reduces time required for image acquisition and data processing.

PMID- 29451725
TI  - Selective C(sp3 )-H Aerobic Oxidation Enabled by Decatungstate Photocatalysis in
      Flow.
AB  - A mild and selective C(sp3 )-H aerobic oxidation enabled by decatungstate
      photocatalysis has been developed. The reaction can be significantly improved in
      a microflow reactor enabling the safe use of oxygen and enhanced irradiation of
      the reaction mixture. Our method allows for the oxidation of both activated and
      unactivated C-H bonds (30 examples). The ability to selectively oxidize natural
      scaffolds, such as (-)-ambroxide, pregnenolone acetate, (+)-sclareolide, and
      artemisinin, exemplifies the utility of this new method.

PMID- 29451727
TI  - Impact of Zeolite Structure on Entropic-Enthalpic Contributions to Alkane
      Monomolecular Cracking: An IR Operando Study.
AB  - The monomolecular cracking rates of propane and n-butane over MFI, CHA, FER and
      TON zeolites were determined simultaneously with the coverage of active sites at
      reaction condition using IR operando spectroscopy. This allowed direct
      determination of adsorption thermodynamics and intrinsic rate parameters. The
      results show that the zeolite confinement mediates enthalpy-entropy trade-offs
      only at the adsorbed state, leaving the true activation energy insensitive to the
      zeolite or alkane structure while the activation entropy was found to increase
      with the confinement. Hence, relative cracking rates of alkanes within zeolite
      pores are mostly governed by activation entropy.

PMID- 29451728
TI  - Phosphinic Acid Based Linkers: Building Blocks in Metal-Organic Framework
      Chemistry.
AB  - Metal-organic frameworks (MOFs) are a chemically and topologically diverse family
      of materials composed of inorganic nodes and organic linkers bound together by
      coordination bonds. Presented here are two significant innovations in this field.
      The first is the use of a new coordination group, phenylene-1,4
      bis(methylphosphinic acid) (PBPA), a phosphinic acid analogue of the commonly
      used terephtalic acid. Use of this new linker group leads to the formation of a
      hydrothermally stable and permanently porous MOF structure. The second innovation
      is the application of electron-diffraction tomography, coupled with dynamic
      refinement of the EDT data, to the elucidation of the structure of the new
      material, including the localization of hydrogen atoms.

PMID- 29451729
TI  - Leadership Competency Expectations of Employers and the Expanding Mission of
      Career Centers.
AB  - This chapter describes the expectations of employers for recent college graduates
      within the current state of higher education, the resulting career readiness
      competencies developed by the National Association of Colleges and Employers, and
      the increasing shift for colleges and universities to recognize career readiness
      as an institutional priority.

PMID- 29451730
TI  - Leveraging a Leadership Development Framework for Career Readiness.
AB  - This chapter provides a context for how colleges and universities can prepare
      students for career readiness by leveraging leadership development programs to
      further develop knowledge, skills, and competencies that translate to the
      changing world of work, particularly for graduates in transition to their first
      jobs.

PMID- 29451731
TI  - Organizational Alignment to Promote Leadership Development for Career Readiness
      in College Settings.
AB  - This chapter describes how three higher education institutions aligned leadership
      development and career readiness. Best practices for the strategic integration of
      leadership development with career development that promote college student
      career readiness are included.

PMID- 29451732
TI  - Editors' Notes.

PMID- 29451733
TI  - An Overview of Leadership Competencies and Assessment Considerations.
AB  - This chapter provides an overview of leadership competencies and ways in which
      colleges and universities can use competency assessment as a tool for current
      leadership education offerings to assist professionals in revising and expanding
      programming to better enable their students to become career ready.

PMID- 29451734
TI  - Promoting Learning, Career Readiness, and Leadership in Student Employment.
AB  - Creating a learning-centric environment for student employees enables work to
      contribute to student success, leadership development, and career readiness.
      Lessons from the IOWA GROW(r) and Illinois Leadership(r) Center programs are
      featured.

PMID- 29451735
TI  - Foreword.

PMID- 29451736
TI  - Enhancing Leadership Competencies for Career Readiness.
AB  - In order to prepare students for their future careers, it is important to
      understand the competencies necessary for career success. This chapter will
      discuss the many ways in which leadership competencies can be utilized to help
      enhance career readiness.

PMID- 29451737
TI  - Mapping Career-Ready Skills Through Student Leadership Programs.
AB  - This chapter discusses connecting learning outcomes already pursued in many
      leadership development programs with the skills that are most in-demand by
      employers. Additionally, the need to holistically map and integrate the career
      skills gained in both curricular and cocurricular contexts is explored, with
      models provided for implementing this approach.

PMID- 29451738
TI  - Well differentiated grade 3 pancreatic neuroendocrine tumors compared with
      related neoplasms: A morphologic study.
AB  - BACKGROUND: Pancreatic neuroendocrine neoplasms with a Ki-67 labeling index
      greater than 20% were reclassified in 2017 by the World Health Organization into
      well differentiated (WD) and poorly differentiated grade 3 neuroendocrine
      carcinoma (NEC). The authors describe the cytologic features of grade 3 WD
      pancreatic neuroendocrine neoplasms compared with grade 2 neoplasms and NEC.
      METHODS: Fine-needle aspirates from 65 pancreatic neuroendocrine neoplasms were
      reviewed, and their cytomorphologic features were compared across grade 2, WD
      grade 3, and PD small cell type (PD-S), large cell type (PD-L), and type not
      otherwise specified (PD-NOS) neoplasms. RESULTS: The 65 aspirates consisted of 19
      grade 2 neoplasms, 32 WD grade 3 neoplasms, and 14 NECs (6 PD-S, 5 PD-L, and 3 PD
      NOS). The medians Ki-67 proliferation index was 11% (range, 3.2%-17%) in grade 2
      neoplasms, 40% (range, 21%-89%) in WD grade 3 neoplasms, 80% (range, 63%-95%) in
      PD-S neoplasms, 39% (range, 25%-61%) in PD-L neoplasms, and 70% (range, 30%-80%)
      in PD-NOS neoplasms. Both grade 2 and WD grade 3 neoplasms were associated with
      plasmacytoid morphology and smooth nuclear contours, but WD grade 3 neoplasms had
      significant increases in abundant cytoplasm (72% vs 17%; P = .007), nuclear
      tangles (75% vs 42%; P = .006), and apoptosis (86% vs 58%; P = .005). Compared
      with NECs, WD grade 3 neoplasms had increased plasmacytoid morphology (75% vs 7%;
      P < .001), smooth nuclear contours (94% vs 64%; P = .02), round nuclei (59% vs
      21%; P = .01), and less pleomorphism (13% vs 50%; P = .004), molding (9% vs 79%;
      P < .001), and necrosis (13% vs 43%; P = .003). WD grade 3 neoplasms had less
      pleomorphism (13% vs 50%; P = .04), less necrosis (13% vs 60%; P = .04), and more
      plasmacytoid morphology (75% vs 20%; P = .03) than PD-L. CONCLUSIONS: The
      prevalence of cytologic features differs in WD grade 3 pancreatic neuroendocrine
      neoplasms compared with grade 2 neoplasms and NECs, and these differences assist
      in the recognition of this newly classified entity. Cancer Cytopathol
      2018;126:326-35. (c) 2018 American Cancer Society.

PMID- 29451739
TI  - Stacking Interactions of Heterocyclic Drug Fragments with Protein Amide
      Backbones.
AB  - Stacking interactions can be important enthalpic contributors to drug binding.
      Among the less well-studied stacking interactions are those occurring between an
      arene and the pi-face of an amide group. Given the ubiquity of heterocycles in
      drugs, combined with the abundance of amides in the protein backbone, optimizing
      these noncovalent interactions can provide a potential route to enhanced drug
      binding. Previously, Diederich et al. (ChemMedChem 2013, 8, 397-404) studied
      stacked dimers of a model amide with a set of 18 heterocycles, showing that
      computed interaction energies correlate with the dipole moments of the
      heterocycles and providing guidelines for the optimization of these interactions.
      We considered stacked dimers of the same model amide with a larger set of 28
      heterocycles common in pharmaceuticals, by using more robust ab initio methods.
      While the overall trends in these new data corroborate many of the results of
      Diederich et al., these data provide a more refined view of the nature of amide
      stacking interactions. We present a robust scoring function for amide stacking
      interaction energies based on the molecular dipole moment and strength of the
      electric field above the arene.

PMID- 29451740
TI  - Caveat Usor: Assessing Differences between Major Chemistry Databases.
AB  - The three databases of PubChem, ChemSpider, and UniChem capture the majority of
      open chemical structure records with February 2018 totals of 95, 63, and 154
      million, respectively. Collectively, they constitute a massively enabling
      resource for cheminformatics, chemical biology, and drug discovery. As meta
      portals, they subsume and link out to the major proportion of public bioactivity
      data extracted from the literature and screening center assay results. Therefore,
      they not only present three different entry points, but the many subsumed
      independent resources present a fourth entry point in the form of standalone
      databases. Because this creates a complex picture it is important for users to
      have at least some appreciation of differential content to enable utility
      judgments for the tasks at hand. This turns out to be challenging. By comparing
      the three resources in detail, this review assesses their differences, some of
      which are not obvious. This includes the fact that coverage is significantly
      different between the 587, 282, and 38 contributing sources, respectively. This
      not only presents the "who-has-what" question, but also the reason "why" any
      particular inclusion is considered valuable is rarely made explicit. Also
      confusing is that sources nominally in common (i.e., having the same submitter
      name) can have significantly different structure counts, not only in each of the
      three but also from their standalone instantiations. Assessing a series of
      examples indicates that differences in loading dates and structural
      standardization are the main causes of this inter-portal discordance.

PMID- 29451741
TI  - Non-invasive optical method for real-time assessment of intracorneal riboflavin
      concentration and efficacy of corneal cross-linking.
AB  - Keratoconus is the primary cause of corneal transplantation in young adults
      worldwide. Riboflavin/UV-A corneal cross-linking may effectively halt the
      progression of keratoconus if an adequate amount of riboflavin enriches the
      corneal stroma and is photo-oxidated by UV-A light for generating additional
      cross-linking bonds between stromal proteins and strengthening the biomechanics
      of the weakened cornea. Here we reported an UV-A theranostic prototype device for
      performing corneal cross-linking with the ability to assess corneal intrastromal
      concentration of riboflavin and to estimate treatment efficacy in real time.
      Seventeen human donor corneas were treated according to the conventional
      riboflavin/UV-A corneal cross-linking protocol. Ten of these tissues were probed
      with atomic force microscopy in order to correlate the intrastromal riboflavin
      concentration recorded during treatment with the increase in elastic modulus of
      the anterior corneal stroma. The intrastromal riboflavin concentration and its
      consumption during UV-A irradiation of the cornea were highly significantly
      correlated (R = 0.79; P = .03) with the treatment-induced stromal stiffening
      effect. The present study showed an ophthalmic device that provided an
      innovative, non-invasive, real-time monitoring solution for estimating corneal
      cross-linking treatment efficacy on a personalized basis.

PMID- 29451742
TI  - Real-time monitoring prefrontal activities during online video game playing by
      functional near-infrared spectroscopy.
AB  - A growing body of literature has suggested that video game playing can induce
      functional and structural plasticity of the brain. The underlying mechanisms,
      however, remain poorly understood. In this study, functional near-infrared
      spectroscopy (fNIRS) was used to record prefrontal activities in 24 experienced
      game players when they played a massively multiplayer online battle arena video
      game, League of Legends (LOL), under naturalistic conditions. It was observed
      that game onset was associated with significant activations in the ventrolateral
      prefrontal cortex (VLPFC) and concomitant deactivations in the dorsolateral
      prefrontal cortex (DLPFC) and frontal pole area (FPA). Game events, such as
      slaying an enemy and being slain by an enemy evoked region-specific time-locked
      hemodynamic/oxygenation responses in the prefrontal cortex (PFC). It was proposed
      that the VLPFC activities during LOL playing are likely responses to visuo-motor
      task load of the game, while the DLPFC/FPA activities may be involved in the
      constant shifts of attentional states and allocation of cognitive resources
      required by game playing. The present study demonstrated that it is feasible to
      use fNIRS to monitor real-time prefrontal activity during online video game
      playing.

PMID- 29451743
TI  - Serum adiponectin and insulin secretion: A direct or inverse association?
AB  - We investigated the association between serum high molecular weight (HMW)
      adiponectin and insulin secretion in a population-based study, with or without
      adjustment for insulin sensitivity. A total of 488 participants (263 women) were
      included in the present study. Insulin secretion was estimated using the
      homeostasis model assessment of beta-cell function +/- adjustment for insulin
      resistance using the disposition index. Multivariate analysis showed that HMW
      adiponectin was significantly and inversely associated with homeostasis model
      assessment of beta-cell function (partial regression coefficient -0.19, 95%
      confidence interval -0.28, -0.10, P < 0.0001). However, HMW adiponectin was
      significantly and positively associated with disposition index (partial
      regression coefficient 0.15, 95% confidence interval 0.06, 0.24, P = 0.0016). The
      present study showed that a positive association between HMW adiponectin levels
      and insulin secretion evaluated using an index incorporating adjustment for
      insulin resistance was identified, and vice versa using an index that did not
      adjust for insulin resistance.

PMID- 29451744
TI  - Design, Synthesis, and Biological Evaluation of Bivalent Ligands Targeting
      Dopamine D2 -Like Receptors and the MU-Opioid Receptor.
AB  - Currently, there is mounting evidence that intermolecular receptor-receptor
      interactions may result in altered receptor recognition, pharmacology and
      signaling. Heterobivalent ligands have been proven useful as molecular probes for
      confirming and targeting heteromeric receptors. This report describes the design
      and synthesis of novel heterobivalent ligands for dopamine D2 -like receptors (D2
      -likeR) and the MU-opioid receptor (MUOR) and their evaluation using ligand
      binding and functional assays. Interestingly, we identified a potent bivalent
      ligand that contains a short 18-atom linker and combines good potency with high
      efficacy both in beta-arrestin 2 recruitment for MUOR and MAPK-P for D4 R.
      Furthermore, this compound was characterized by a biphasic competition binding
      curve for the D4 R-MUOR heterodimer, indicative of a bivalent binding mode. As
      this compound possibly bridges the D4 R-MUOR heterodimer, it could be used as a
      pharmacological tool to further investigate the interactions of D4 R and MUOR.

PMID- 29451745
TI  - Detection of ROS1-positive non-small cell lung cancer on cytological specimens
      using immunocytochemistry.
AB  - BACKGROUND: Rearrangements of the ROS1 oncogene are found in 1% to 2% of non
      small cell lung cancers (NSCLC) and are regarded as mutually exclusive oncogenic
      driver mutations. Since the approval of targeted therapy for ROS1-positive NSCLC,
      ROS1 testing has become a part of the diagnostic routine. Fluorescence in situ
      hybridization (FISH), optionally selected for by immunohistochemistry on
      histological material, is a common practice for the detection of ROS1
      rearrangements. However, NSCLC often is diagnosed by cytology alone, requiring
      predictive marker testing on cytological specimens. In the current study, the
      authors explored the accuracy of ROS1 immunocytochemistry (ICC) on non-cell block
      cytological specimens for the detection of ROS1 rearrangements. METHODS: ICC
      using the D4D6 antibody on an automated immunostainer was performed prospectively
      in the routine diagnostic setting on cytological specimens from 295 patients with
      NSCLC, including adenocarcinoma (241 patients), NSCLC not otherwise specified (50
      patients), and other malignancies (4 patients). Any immunostaining was considered
      positive. RESULTS: ICC was positive in all 13 ROS1-rearranged NSCLC cases
      confirmed by FISH (12 cases) or next-generation sequencing (1 case). Confirmation
      of 282 ICC-negative cases was available for 208 patients. The sensitivity,
      specificity, and positive and negative predictive values for ROS1 ICC compared
      with the final ROS1 status all were 100%. CONCLUSIONS: ROS1 ICC is an accurate
      method for the detection of ROS1 rearrangements in NSCLC. Given the high costs
      and technical challenges of FISH and the rarity of ROS1 rearrangements, ICC is
      rapid and therefore well suited as a screening method. Cases with equivocal or
      positive findings on ICC can be confirmed by FISH or molecular tests. Cancer
      Cytopathol 2018;126:421-9. (c) 2018 American Cancer Society.

PMID- 29451746
TI  - Bracing for disaster: Specialists step up their preparations for emerging and
      evolving infectious disease threats.

PMID- 29451747
TI  - Our 2017 Cancer Cytopathology Young Investigator.

PMID- 29451748
TI  - Morphological, molecular characterization and taxonomic status of Triplophysa
      marmorata and Triplophysa kashmirensis (Cypriniformes: Nemacheilidae) from
      Kashmir valley, India.
AB  - In India the distribution of genus Triplophysa has been reported only in the
      upper drainage of theIndus River in Jammu and Kashmir and Lahul and Spiti area of
      Himachal Pradesh. There is no study on thetaxonomic characterization of this
      genus from Kashmir Himalaya. Therefore the present study was aimed tocharacterize
      two important fish species Triplophysa marmorata and T. kashmirensis from Kashmir
      valley, byusing morphometric and molecular tools. It is difficult to discriminate
      these two species due to the poor qualityof original descriptions, and the lack
      of good reviews. Keeping this in view, a morphometric and molecularstudy was
      conducted. Morphometric data were analyzed by using univariate analysis of
      variance (ANOVA) andmultivariate analyses (Principal component analysis) and
      mtDNA marker Cytochrome oxidase 1 was used formolecular support. Altogether, 22
      morphometric characters were used and 15 characters were found
      significantlyvariable (P < 0.05). First two components of principal component
      analysis (PCA) i.e. PC1 and PC2 groupedthese two species into separate clusters.
      The Cytochrome oxidase 1 analysis showed that the mean intraspecificnucleotide
      divergence (K2P) was 0.001 and interspecific nucleotide divergence was 0.007.
      Despite havinglow K2P divergence, these two species got separated into two
      distinct clades in both Neighbour joining (NJ)and Unweighted Pair Group Method
      with Arithmetic Mean (UPGMA) tree building methods. But the patternof clade
      formation showed that these species were recently radiated from each other and
      may have the sameancestor. Furthermore, these two species were found closer to
      Nemacheilidae than to Balitoridae family inthe phylogenetic analysis. The
      molecular divergence between these species was also supported by variance
      inmorphometric data. This work may build the base for the revision of taxonomic
      identity of these two importantfishes of genus Triplophysa. The present
      investigation formulated that, based on morphological and mtDNA COIsequences
      analysis, these two taxonomic Triplophysa species should be considered as valid.
      The results may furtherassist to enhance the knowledge of the ichthyologists in
      understanding the ichthyofauna of Kashmir Valleyand will help them in planning
      strategies for conservation and management of these less studied small
      indigenousspecies along their natural range of distribution.

PMID- 29451749
TI  - Seed colour affects light and temperature requirements during germination in two
      Lotus species (Fabaceae) of the Arabian subtropical deserts.
AB  - Heterogeneity in seeds mostly occurs due to physiological, environmental and
      genetic factors, andthese could affect seed dormancy and germination. Therefore,
      the aim of our study was to assess the effect ofseed colour on germination
      behavior. For this, both light and temperature requirements were assessed in
      Lotusglinoides and Lotus halophilus (Fabaceae) from the hyper-arid deserts of the
      United Arab Emirates. Germinationwas assessed in terms of both final germination
      level (percentage) and germination rate, as expressed byTimson's germination
      velocity index. Lotus glinoides produces black and yellow-colored seeds, and L.
      halophilusproduces green and yellow seeds. Different seed lots were germinated in
      both light and darkness at differenttemperatures. Yellow seeds of the two species
      attained significantly lower germination, compared to black andgreen seeds. There
      was no specific light or temperature requirements for the germination of the two
      colouredseeds of L. glinoides; the effect of interactions between seed colour and
      both light and incubation temperature,were not significant on the final
      germination percentage. In L. halophilus, green seeds germinated
      significantlymore in both light and darkness at lower temperatures (15/25 
      degrees C) and in light at higher temperatures (25/35 degrees C), compared to
      yellow seeds. Yellow seeds germinated faster, compared to black at 15/25  degrees
      C in L. glinoidesand compared to green seeds at 15/25  degrees C and 25/35 
      degrees C in L. halophilus. Seed colour variation, at least in L.halophilus,
      could be a survival strategy that would determine the time of germination
      throughout the year in theunpredictable desert environment.

PMID- 29451750
TI  - Comparison of forest regeneration in two sites with different primate abundances
      in Northwestern Ecuador.
AB  - There is increasing evidence that large-bodied primates play important roles as
      seed dispersers andin the maintenance of tree diversity in forest ecosystems. In
      this study we compared forest regeneration at twosites with differing primate
      abundances in the Ecuadorian Chocoan rainforest. We predicted: (1) significant
      differencesin primate abundance between the two sites; (2) higher understory tree
      species richness and density atthe site with greater primate abundance; (3) the
      site with lower primate abundance characterized by tree speciesdispersed by non
      primate biotic agents and/or abiotic factors. We compared two sites, Tesoro
      Escondido (TE)a campesino cooperative, and the El Pambilar (EP) wildlife refuge
      that both maintain populations of mantledhowler monkey (Alouatta palliata), the
      brown-headed spider monkey (Ateles fusciceps fusciceps) and the capuchinmonkey
      (Cebus capucinus). We characterized canopy structure by point-quadrant sampling,
      determinedprimate abundance and sampled seedlings/saplings in 1 m2 plots,
      classifying tree species based on three dispersalsyndromes: adapted for primate
      dispersal, dispersed by other biological agents, and abiotic dispersal. We
      comparedsites in terms of primate abundance (groups and individuals observed per
      day) and regeneration characteristics(overall density, species richness, and
      dispersal syndrome). We carried out within site comparisons andconstructed
      understory tree species accumulation curves. Overall the forests were
      structurally similar - with significantlyhigher densities of A. f. fusciceps at
      TE. Encounter rates for the other two primate species were similarat both sites.
      Understory tree density and species richness was significantly higher in TE with
      no stabilization oftree species accumulation curves. The species accumulation
      curve for understory trees at EP stabilized. Higherdensities and species richness
      of primate dispersed tree species were observed at TE, with non-primate
      bioticallydispersed tree species the dominant dispersal syndrome at both sites.
      Our observations are consistent with thosefrom other studies investigating the
      role of large-bodied frugivorous primates in forest regeneration, and pointto a
      general pattern: future lowland tropical forest tree diversity depends on
      maintaining robust populations oflarge primate species in these systems. It is
      highly probable that the maintenance of high levels of tree diversityin Chocoan
      rainforests is dependent on the conservation of its largest resident primate, the
      critically endangeredbrown-headed spider monkey (A. f. fusciceps).

PMID- 29451751
TI  - Resource allocation in Copaifera langsdorffii (Fabaceae): how supra-annual
      fruiting affects plant traits and herbivory?
AB  - Plants have limited resources to invest in reproduction, vegetative growth and
      defense against herbivorous.Trade-off in resources allocation promotes changes in
      plant traits that may affect higher trophic levels.In this study, we evaluated
      the trade-off effect between years of high and low fruiting on the investment
      ofresources for growth and defense, and their indirect effects on herbivory in
      Copaifera langsdorffii. Our questionswere: (i) does the resource investment on
      reproduction causes a depletion in vegetative growth as predicted bythe
      Carbon/Nutrient Balance hypothesis (CNBH), resulting in more availability of
      resources to be allocated fordefense?, (ii) does the variation in resource
      allocation for growth and defense between years of high and lowfruiting leads to
      indirect changes in herbivory? Thirty-five trees located in a Cerrado area were
      monitored during2008 (year of high fruiting) and 2009 (year of no fruiting) to
      evaluate the differential investment in vegetativetraits (biomass, growth and
      number of ramifications), plant defense (tannin concentration and plant
      hypersensitivity)and herbivory (galling attack and folivory). According to our
      first question, we observed that in thefruiting year, woody biomass negatively
      affected tannin concentration, indicating that fruit production restrictedthe
      resources that could be invested both in growth as in defense. In the same way,
      we observed an inter-annualvariation in herbivorous attack, and found that plants
      with higher leaf biomass and tannin concentration, experiencedhigher galling
      attack and hypersensitive reaction, regardless years. These findings suggested
      that plants'resistance to herbivory is a good proxy of plant defense and an
      effective defense strategy for C. langsdorffii,besides the evidence of indirect
      responses of the third trophic level, as postulated by the second question.
      Insummary, the supra-annual fruiting pattern promoted several changes on plant
      development, demonstrating theimportance of evaluating different plant traits
      when characterizing the vegetative investment. As expected bytheory, the trade
      off in resource allocation favored changes in defense compounds production and
      patterns ofherbivory. The understanding of this important element of insect-plant
      interactions will be fundamental to deciphercoevolutionary life histories and
      interactions between plant species reproduction and herbivory. Besidesthat, only
      through long-term studies we will be able to build models and develop more
      accurate forecasts aboutthe factors that trigger the bottom-up effect on
      herbivory performance, as well the top-down effect of herbivoreson plant trait
      evolution.

PMID- 29451752
TI  - Cellular development of the germinal epithelium during the gametogenic cycle of
      the golden mussel Limnoperna fortunei (Bivalvia: Mytilidae).
AB  - The golden mussel Limnoperna fortunei is an invasive species that has quickly
      dispersed and colonized several potential different habitats distributed all over
      the world, causing environmental and economic impacts. Thus, in order to
      contribute to a better understanding of the reproductive aspects of L. fortunei,
      we described the cellular dynamic of the male and female germinal epithelium
      during the annual reproductive life history of this species, with the use of high
      resolution histology. An approximate of 1 200 specimens of L. fortunei were
      sampled periodically on the upper Parana River floodplain (Brazil), from March
      2010 to December 2012. Based on the activity of the germinal epithelium and
      consequent germ cell development, this study has resulted in the recognition of
      the following reproductive phases: Developing, Spawning Capable, Regressing and
      Regenerating. In the characterization of these phases, the following germ cells
      were described for males: spermatogonia, primary and secondary spermatocytes,
      spermatids and spermatozoa. Cell nests, oogonia, early prophase oocytes,
      previtellogenic oocytes and vitellogenic oocytes (early vitellogenic oocytes,
      middle vitellogenic oocytes and full-grown oocytes) were described for females.
      The morphological data and reproductive parameters obtained, showed the value of
      the cellular dynamics of the germinal epithelium, for the understanding of the
      cyclic gonadal events during the adult reproductive life of the mollusk in
      general. These results on the gametogenesis of this invasive species may be a
      fundamental tool for the development of control strategies and programs
      implementation, to reduce their proliferation and impacts in natural local
      environments.

PMID- 29451753
TI  - Early larvae ontogeny of the Neotropical fishes: Prochilodus costatus and P.
      argenteus (Characiformes: Prochilodontidae).
AB  - Early development of fish larvae is a highly dynamic process and its study may
      provide importantinformation about ontogenetic development, bioenergetic growth,
      behaviour, taxonomic characteristics for identificationin natural environments,
      identification of spawning areas, and population monitoring. With the aim
      toprovide knowledge about their growth and behaviour, to support larval rearing,
      and also taxonomic purposes, westudied the life history of the Prochilodus
      argenteus and P. costatus from hatching until the complete absorptionof the yolk.
      Larvae were obtained through artificial reproduction at the Hydrobiology and
      Aquaculture Stationof Tres Marias, Minas Gerais, Brazil. Immediately after
      hatching, 100 larvae of each species were put in twoplastic incubators for
      conditioning. On a daily basis, larvae behavior was recorded and 14 larvae of
      each specieswere collected to analyse body morphology. On the first day after
      hatching, larvae of P. costatus and P. argenteusshowed an elongated and
      transparent body; the yolk sac was filled with individualized yolk globules. In
      bothspecies, the embryonic fin rounded the caudal region of the body, the retina
      was non-pigmented and the gut wasobliterated. At the second day post-hatching,
      larvae of both species dendritic chromatophores had emerged, themouth was
      obliterated and the pectoral fin was observed. The larvae showed 38-43 myomeres
      in P. costatus and42-43 in P. argenteus. For both species, the gas bladder was
      inflated and the lumen of the gut was already open.On the third day post
      hatching, the mouth of P. costatus and P. argenteus was already open in a sub
      terminalposition; the retina was pigmented; the gill arches had lamellar
      protrusions and were partially covered by theoperculum. On the fourth day post
      hatching, the pigmentation pattern was maintained with greater intensity;
      themouth occupied a terminal position, the yolk sac was almost completely
      reabsorbed, and the pectoral and caudalfins showed mesenchymal rays in both
      species. The gut showed a broad lumen with folded mucosa and epitheliumwith
      striated border. The larvae of both species showed similar swimming behaviour.
      Our study providedunderstanding about the morphophysiological aspects, species
      identification, larval development and growth,and the ontogenic characteristics
      of two Neotropical fishes with importance for commercial and sports fishing.

PMID- 29451754
TI  - Biological aspects and mating behavior of Leucothyreus albopilosus (Coleoptera:
      Scarabaeidae).
AB  - The genus Leucothyreus has been linked to some commercial plant crop pests.
      Eventhough severalspecies have been described for this genus, information about
      this group is still scarce. This study investigatedsome biological aspects and
      mating behavior in Leucothyreus albopilosus. Studies were conducted at the
      StateUniversity of Mato Grosso do Sul, in the municipalities of Aquidauana and
      Cassilandia, MS, Brazil. For biologicalstudies, adults were collected with light
      traps from February 2011 to February 2012, and for behavioranalyses from
      September to December 2014. Biological studies were undertaken every three days
      and includedthe eggs inspection, and the separation of the newly hatched larvae
      to observe and describe their developmentalstages; to monitor larval growth and
      differentiate larval instars, we measured the larvae cephalic capsule. Lifecycle
      was determined starting from the newly laid eggs until adult death. For mating
      behavior studies, adultsobtained with light traps were taken to the laboratory.
      As soon as they started flying in the evening, couples wereformed and copulation
      steps were recorded. In the field, we observed that adults were mostly collected
      duringwarmer and wetter periods (from August to March). Our results showed that
      the embryonic period of L. albopilosuslasted 20.5 days, the 1st, 2nd and 3rd
      instars lasted 31.0, 33.1 and 85.6 days, respectively. The pupal stagelasted 20
      days, and the egg to adult period was completed in 185.5 days; these results
      suggest that L. albopilosuscan be characterized as a univoltine species.
      Observations of mating behavior in the laboratory showed that, afterthe sunset,
      adults projected a small portion of clypeus near the soil surface and flew off
      seeking a female to mate.The female could accept or reject the male for mating.
      When the female accepted the male, copulation occurredfrom 19:00 to 23:00 hours,
      and lasted 19.45 minutes on average. Sometimes females refused to mate,
      probablybecause the male or female were not sexually mature to perform
      copulation, and there might be a chemicalcommunication between the adults. Adults
      were observed feeding on ripe bananas (Musa sp., Musaceae) and onmangaba flowers
      (Hancornia speciosa, Apocynaceae) in the laboratory. With this work we
      contributed with thedescription of mating behavior in the genus Leucothyreus and
      concluded that the biological cycle was completedin less than 200 days.

PMID- 29451755
TI  - [Metazoan parasites of Micropterus salmoides (Centrarchidae: Perciformes) from
      reservoirs of Nuevo Leon, Mexico and their association with condition factor and
      gender].
AB  - The largemouth bass Micropterus salmoides is a very valuable fish species for
      aquaculture and sport fishing; however, there are nosystematic studies on fish
      metazoan parasites in Mexico. The main objective of the present study was to
      describethe prevalence, abundance, and intensity of M. salmoides metazoan
      parasites, and their association with fishcondition factor and gender. The sample
      size was composed by 672 hosts, collected between 2011-2013 from thefollowing
      reservoirs of Nuevo Leon, Mexico: Rodrigo Gomez dam ("La Boca", LB), Cuchillo
      Solidaridad dam(CS), Salinillas lagoon (LS), Mariano Escobedo dam
      ("Sombreretillo", S), and Jose Lopez Portillo dam ("CerroPrieto", CP). Living
      fish were transported to the laboratory; sizes and weights were then recorded to
      calculatethe Fulton condition factor (k). If possible, gender was also recorded.
      Parasites were detected under stereoscopy,recollected and preserved by
      traditional techniques. Statistical analysis of association between parasitic
      load,gender, and Fulton condition factor were calculated, using the X2 and the
      Student-t tests. Results showed that 12different metazoans were identified, two
      flukes (Posthodiplostomum minimum centrarchi and Phyllodistomumpearsei), one
      tapeworm (Proteocephalus ambloplitis), three roundworms (Contracaecum sp.,
      Spinitectuscarolini and Philometra nodulosa), two acantocephalan
      (Neoechinorhynchus cylindratus and Arhythmorhynchussp.), one leech (Myzobdella
      moorei), and three copepods (Ergasilus versicolor; Ergasilus arthrosis and
      Ergasiluscerastes). HSD Tukey test showed that infected fish from LB were
      significantly different than LS, CS, CP,and S (P<0.05). Parasites most commonly
      collected in all five locations were P. m. centrarchi, Contracaecumsp. and E.
      versicolor. The frequency of P. m. centrarchi was highly significant (P<0.001)
      than other parasites;furthermore, this parasite showed the highest prevalence
      (97.5 %), abundance (10.12-83.6), and intensity(15.44-88.5). Statistical
      dependence was found between intensity and abundance of metazoans with regard
      tofemale gender and size on five reservoirs (t=143.82, P=0.0001; t=2.6, P=0.01,
      respectively). In addition, theabundance and intensity showed statistical
      dependence with regard to k, which was proportionally significant.New locality
      records for Nuevo Leon include P. m. centrarchi, P. pearsei, P. ambloplitis,
      Contracaecum sp.,Arhythmorhynchus sp., and E. cerastes. Furthermore, P. nodulosa,
      S. carolini, N. cylindratus, and E. arthrosiswere new records for Mexico.

PMID- 29451756
TI  - The diversity of ant communities (Hymenoptera: Formicidae) and their connections
      with other arthropods from three temperate forests of Central Mexico.
AB  - Ants have been considered useful for bioindication because of their ecological
      characteristics.Nonetheless, among the characteristics of a bioindicator group,
      there must be a consistent and replicableresponse to disturbance. In this sense,
      divergent reactions have been found, even between taxons narrowlyrelated. The
      objective of this work was to compare the diversity of the ant communities in
      three different temperateforests with different levels of disturbance, and to
      correlate their abundance and diversity of species, withthat found in other
      arthropod communities of the same forests. The work was carried out in three
      municipalitiesin the North of the State of Mexico, where three types of different
      forests were identified by their degree of disturbance.These types include: 1)
      primary forest (PF), with typical species of a conserved forest; 2) mixed
      forest(MF), with species of a conserved forest and a reforestation effort; and 3)
      reforested forest (RF), with speciesused in reforestation efforts and indicative
      of disturbance. In each sample, an area of 2 500 m2 was selected. Eacharea had 16
      pitfalls apiece and they were placed 10 m away from each other. Samples were
      collected twice; onefrom February through March 2009 (dry season) and another
      from August through September 2010 (rainy season),which produced a total of 192
      traps. Obtained specimens were identified at the most taxonomically
      specificlevel. All data captured was transformed to ?n + 0.5 and diversity index
      levels of Shannon and Simpson werecalculated, as well as richness of species for
      ants, beetles, grasshoppers, true bugs, and spiders. The values ofrichness,
      diversity, and abundance were correlated with the Pearson coefficient, and to
      evaluate possible causalrelationships between these, a path analysis was
      performed. Results suggested an important influence of the siteover ant
      communities, and values of richness, abundance and diversity were correlated with
      the communities ofspiders, beetles, grasshoppers and true bugs, but not for all
      the sites studied. Responses to environmental changesare not only on the numeric
      proportions of abundance, richness and diversity, but also in the indirect and
      casualecological interactions. Finally, the data seems to indicate that the
      responses of the ants to the environmentalchanges are not necessarily reflected
      on other organisms' communities, so the ants' role as bioindicators can
      belimited.

PMID- 29451757
TI  - [Taxonomic and functional diversity of the bycatch fishes community of trawl
      fishing from Northern Gulf of California, Mexico].
AB  - The Northern Gulf of California (NGC) is a mega diverse area of highendemism with
      major economic interest because of the multi-specific fisheries developed, mainly
      shrimp.There is a lack of recent studies on bycatch fish assemblages, so during
      the fishing seasons from 2009-2010 and2010-2011, on board 13 shrimp boats, 14
      commercial fishing trips were performed from 5 m - 90 m in depthwith a total of
      119 catches. The 119 catches were analyzed to assess fish community structure
      using taxonomicdiversity indices to detect changes in the community following the
      taxonomic distinctness average Delta+ and thediversity index Delta* (TAXDEST of
      the PRIMER v6 program). To confirm the structure of functional groups,
      weconsidered similarities of ecologic and morphologic traits among species. The
      results showed that the indicesDelta+ and Delta* were within the expected average
      and confidence intervals at 95%, finding significant differencesbetween the
      indices. The analyses showed a well-structured community because of the great
      variety of formsand functions of the species within the community. In the
      community of the functional groups, reproduction wasthe ecological attribute that
      contributed the most to their structure. The community structure was represented
      byintermediate trophic levels (3-3.9), preferably primary and secondary
      carnivores within the trophic categories ofpredators of benthic ichthyo-fauna
      that belong to demersal species of soft bottoms and mostly fusiform body.
      Toconclude, the NGC showed high functional redundancy according to the estimated
      functional groups, thus theecosystem was considered stable and with great
      diversity. This type of studies should be followed using fishingand environmental
      effort due to the great biological and ecologic importance in the area.

PMID- 29451758
TI  - [Feeding of Characidium rachovii (Characiformes: Crenuchidae) and Pyrrhulina
      australis (Characiformes: Lebiasinidae) in shallow lakes of Corrientes,
      Argentina].
AB  - Fishes display diverse feeding strategies that may undergo modifications through
      ontogeny or seasonally with ecological implications in thefood webs. Even though
      the significance of fishes as top predators is recognized, the diet of many of
      them isstill scarcely known; especially in fish that inhabit shallow lakes
      densely vegetated. The aim of this study wasto investigate the diet of
      Characidium rachovii and Pyrrhulina australis of different size classes (I, II
      and III);during winter and summer, and estimate their trophic niche breadth. The
      field work was carried out in two shallowlakes fed by rain (Soto and Pampin lake,
      Corrientes province), from July 2011 to August 2012. The stomachcontents of 104
      individuals of C. rachovii and 91 specimens of P. australis were examined.
      Accumulation curveshowed that the number of analyzed stomachs was representative
      for both species. Twenty three food itemsfor C. rachovii and twenty eight for P.
      australis were recognized in the gut contents. According to the index ofrelative
      importance (IRI), both species feed preferably on cladocerans and midges
      (Chironomidae), and bothspecies showed a large overlap in their diets (85 %),
      according to Morisita index. However the diversity of fooditems and the trophic
      niche breadth of P. australis (1D = 8.86; B = 4.76) were higher than C. rachovii
      (1D =3.37; B = 2.25). Significant differences were observed in the diet of three
      sizes of P. australis (chi2, p < 0.01) andbetween the sizes I and III of C.
      rachovii (chi2, p = 0.03). In both species the diversity of food items increased
      withincreasing their size. Between seasons, the diet differences were significant
      for both species (chi2, p < 0.0001).The high feeding overlap indicates that both
      species mostly use the same resources. Notwithstanding this, boththe number of
      food items as the diversity and breadth of the trophic niche, suggest that these
      species use differentfeeding strategies, C. rachovii showed a trend towards
      specialization in microcrustacean consumption; while P.australis exhibited a
      broader trophic spectrum, incorporating insects from littoral areas and from the
      terrestrialcommunity. The loss of the trophic dominant resource, by increasing
      urbanization on the margin of the studiedshallow lakes, could lead to increased
      competition, due to the wide diet overlap in both species.

PMID- 29451759
TI  - [Reproductive effort, fattening index and yield of Arca zebra (Filibranchia:
      Arcidae) by length and its association with environmental variables, Sucre,
      Venezuela].
AB  - Arca zebra is a mollusk of commercial value and a major socioeconomic fishery in
      Northeastern Venezuela. The present study aimed to evaluate thereproductive
      effort (RE), fattening index (FI) and yield (Y) in different size groups of A.
      zebra from the morroChacopata, Venezuela. For this, monthly samplings from June
      2008 and June 2009, were undertaken, and thebivalves obtained were distributed in
      three length groups: I (30.1 to 50.0 mm), II (50.1 to 70.0 mm) and III (>70.0
      mm). Monthly RE, FI and Y were determined based on bivalve changes in volume of
      fresh meat (VFM),intervalvar volume (IV), dry gonad biomass (DW), dry biomass of
      the organism without gonad (DWs), freshbiomass of meat (FBM) and total biomass
      including shell (TBIS). Besides, environmental variables such astemperature,
      salinity, dissolved oxygen, total organic and inorganic seston and chlorophyll a
      were measuredmonthly. There was great variation in the DW between length groups
      (relevant for II and III): increased fromJune until late September 2008, was
      followed by a marked decrease in October 2008, recovered in the followingmonths,
      and decreased in January 2009, with a slight increase until May 2009; these
      changes were associatedwith variations in sea temperature. The weight of the
      gonad (DW) influenced the RE, FI and Y, as these reachedtheir peaks in the months
      where there was higher gonadal production, indicating the influence of
      temperature onA. zebra reproduction.

PMID- 29451760
TI  - [Reproduction of Saccodon dariensis (Teleostei: Parodontidae) in Guatape River
      tributaries, Magdalena River basin, Colombia].
AB  - The Andean mountain region of Colombia has a high diversity of fish,with high
      number of endemic species. To promote their protection and conservation, the
      knowledge of theirgeneral and reproductive biology is necessary. With this aim,
      the reproductive biology of Saccodon dariensis,in the Penoles and El Cardal
      creeks, Guatape River mid-basin, Magdalena River Basin, was studied, to
      determinereproductive differences between individuals with different oral
      polymorphism (morpho I vs. morpho IV,according to Roberts, 1974), and to define a
      possible spatial or temporal reproductive isolation. Ten field samplingswere
      carried out between October 2007 and February 2012, in periods of rain (October
      and November2007, May 2008 and November 2011), dry (January and March 2010,
      February 2012), transition from rain todry (June 2011) and transition from dry to
      rain (March 2008 and September 2011). Samples were caught usingelectrofishing
      equipment and cast nets (10 mm between knots). A total of 468 specimens were
      analyzed, 268of which were females and 200 males. The average catch size for the
      total number of individuals studied was109.6 mm SL (65.5-174.0 mm), with 108.0 mm
      SL for females (67.7-174.0) and 111.9 mm SL (65.5-149.4)for males. Females
      predominated in the catches, and the sex ratio of 1.0:1.34 significantly deviated
      from thetheoretical distribution 1:1. Similarly, morpho IV predominated in the
      catches, and morphs ratio was 1.00:1.48.Based on the monthly evolution of the
      gonadosomatic index (GSI) and the proportion of mature specimens, thespawning
      season occurs during periods of transition from dry to rainy season when water
      level begins to raise.The lowest values of the condition factor that match the
      maximum values of GSI, indicates that this speciesaccumulated body energy
      reserves that are used during the gonadal maturation and spawning. The mean
      sizeat sexual maturity (L50) was 88.8 mm SL in females and 109.3 mm SL in males.
      The fecundity of S. dariensisfluctuated between 1 137 and 39 303 (mean = 8 309,
      SD = 9 021) and the relative fecundity between 144 and1 131 oocytes/g of total
      weight (mean = 439 +/- 212). The diameter of the oocytes was 0.54 mm (SD =
      0.07).Different development in oocytes was not observed, suggesting massive
      spawning. The coexistence of the twomorphs, external fertilization and
      simultaneous occurrence of reproductive peaks found in this study did notprovide
      support for a possible spatial or temporal reproductive isolation of morphotypes.

PMID- 29451761
TI  - Rubiaceae in Brazilian Atlantic Forest remnants: floristic similarity and
      implications for conservation.
AB  - Brazil holds most of the Atlantic Forest Domain and is also one of the Rubiaceae
      diversity centers inthe Neotropics. Despite the urban expansion in the state of
      Rio de Janeiro, large areas of continuous vegetationwith high connectivity degree
      can still be found. Recently, new Rubiaceae species have been described in the
      Riode Janeiro flora, which present small populations and very particular
      distribution. The current paper analyzedthe similarity in the floristic
      composition of the Rubiaceae in eight Atlantic Forest remnants of Rio de
      Janeirostate protected by Conservation Units. We also surveyed and set guidelines
      for conservation of microendemicspecies. The similarity analysis were based on
      previously published studies in Area de Protecao Ambientalde Grumari, Area de
      Protecao Ambiental Palmares, Parque Estadual da Serra da Tiririca, Parque
      Nacional doItatiaia, Parque Nacional de Jurubatiba, Reserva Biologica de Poco das
      Antas, Reserva Biologica do Tingua andReserva Ecologica de Macae de Cima - using
      the PAST software ("Paleontological Statistics") with Sorensencoefficient. The
      floristic similarity analysis revealed two groups with distinct physiographic
      characteristics anddifferent vegetation types. Group A consisted in two Restinga
      areas, Area de Protecao Ambiental de Grumariand Parque Nacional de Jurubatiba,
      which showed strong bootstrap support (98 %). Group B included forestremnants
      with distinct phytophisiognomies or altitudes, but with moderate bootstrap
      support. Low similaritylevels among the eight areas were found due to the
      habitats' heterogeneity. The current study pointed out 19microendemic species
      from the Atlantic Forest, they present a single-site distribution or a
      distribution restrictedto Mountain and Metropolitan regions of Rio de Janeiro
      state. Concerning the conservation status of microendemicspecies, discrepancies
      between the Catalogue of Flora of Rio de Janeiro and the Red Book of
      BrazilianFlora (two of the main reference catalogs of Brazilian flora) have been
      identified. We have also highlighted theneed for recollecting microendemic
      species from the Atlantic Forest, and for properly assessing the degree ofthreat
      faced by these taxons early.

PMID- 29451762
TI  - [Morfogeometry shell crab Damithrax spinosissimus (Decapoda: Mithracidae) on
      three islands in the southwestern Caribbean].
AB  - The Caribbean King Crab, Damithrax spinosissimus is a fishery resource, butfew
      biological studies are available. Its patchy distribution, and the high
      environmental heterogeneity due to theoceanographic, landscape, and ecological
      characteristics of the Caribbean Sea, can favor the phenotypic
      variabilityaccording to the geographic origin. For this reason, the objective of
      our study was to determine morphometicvariability in the carapace of the crabs
      from three Southwestern Caribbean islands: Providence, Rosario and SanBernardo.
      The former has an oceanic influence, whereas the two latter islands, which are
      closer to the mainland,have more influence of the coastal dynamic. A total of 276
      individuals from the three islands were captured andphotographed: 103 females and
      173 males; their variation was analyzed from 12 anatomical landmarks markedon one
      half of the carapace. The differences in the carapace size were calculated using
      a Fisher's pairwise comparison;the allometric effect was calculated by
      Multivariate Regression Analysis; and the Allometric model viaMultivariate
      Analysis of Covariance. The average shape was calculated from the relative wraps
      RW obtainedthrough PCA analysis; and the Euclidian distances between the shape
      averages, were used to construct a treeusing the Neighbour-Joining algorithm over
      10 000 permutations. The results showed significant differences inthe size and
      shape of the carapace between sexes and among the three islands. The differences
      in the shape ofthe crabs from Providencia were significantly greater than those
      found between the crabs of Rosario and SanBernardo. These results can be
      explained inclusively due to the genetic differences and phenotypic plasticity,
      dueto environmental heterogeneity of the sector. This study, the first of its
      kind, is a contribution to the knowledgeof the species. We concluded that
      different management strategies should be differently adopted in each of thethree
      studied islands.

PMID- 29451763
TI  - Biogeographical affinities of fish associated to the shrimp trawl fishery in the
      Gulf of Tehuantepec, Mexico.
AB  - Fish by-catch of shrimp fishery from the Gulf of Tehuantepec is composed of
      several species that aremainly discarded. In this study, fish by-catch species
      composition, distribution and biogeographical affinitieswere analyzed. For this,
      a total of 15 cruises were carried out on the continental shelf, at depths from
      15 to 64 m,during 2003, 2004, 2005 and 2013. Results showed that fish by-catch
      was represented by 58 families, 129 generaand 242 species. The families
      Haemulidae, Sciaenidae, Paralichthyidae, Gerreidae and Carangidae accounted for>
      70 % of the catch. Haemulopsis axillaris, Syacium ovale, Selene peruviana,
      Diapterus peruvianus, Larimusacclivins and Stellifer erycimba were the most
      frequent species at < 40 m depth (inner shelf), and Prionotusstephanophrys,
      Scorpaena russula, Porichthys analis and Synodus scituliceps were dominant at 40
      60 m depth(outer shelf). Analysis of biogeographical affinities showed that 36.1
      % of species had a wide distribution, fromSan Diego Province to the Panamic
      Province, while 13.2 % had a restricted distribution in the Mexican andPanamic
      Provinces. The ichthyofaunal composition was markedly influenced by the local
      environment andseasonal conditions.

PMID- 29451764
TI  - Interactions between frugivorous bats (Chiroptera: Phyllostomidae) and Piper
      tuberculatum (Piperaceae) in a tropical dry forest in Valle del Cauca, Colombia.
AB  - In any ecosystem, fruits are resources that vary in time and space as well as in
      nutritional content.Coexistence of species from a trophic guild depends on the
      division and use of resources. Therefore, the organismsthat depend on them as a
      food source, tend to show a certain degree of specialization. This way,
      understandingthe factors that influence the dynamics of seed dispersal is
      important for the regeneration and conservationof tropical ecosystems. Our aim
      was to determine variation in consumption of Piper tuberculatum by fruit
      batassemblages in the village of Robles (Jamundi, Valle del Cauca, Colombia). P.
      tuberculatum is a resource usednot only by wildlife but also by people in the
      village of Robles. Bats were captured in mist nets between June andNovember 2014,
      their feces were collected, and the length of the forearm, wing area, leg length
      and mass wererecorded. At the Universidad del Valle seed laboratory, fecal
      samples were washed, and their content determined.Of the 14 species captured,
      Sturnira lilium, Carollia brevicauda, Carollia perspicillata and Artibeus
      lituratusshowed signs of having consumed P. tuberculatum. Sturnira lilium was the
      main consumer of P. tuberculatumfruits, with the greatest number of consumption
      events of fruit from this plant species, whereas the other batsshowed more
      diversified consumption events. The greatest niche overlap was recorded between
      C. brevicaudaand C. perspicillata, species that showed similar sizes (i.e., wing
      area and forearm length) followed by S. liliumand C. perspicillata. In contrast,
      A. lituratus showed the least niche overlap with the other three fruit bats
      captured.In conclusion, Sturnira lilium showed an interaction Sturnira-Piper,
      which is the result of low Solanumavailability, and this bat species was the
      largest consumer of P. tuberculatum in the region.

PMID- 29451765
TI  - [Trophic structure of river fish from Corral de San Luis, Magdalena river basin,
      Colombia Caribbean].
AB  - Ecological studies of species, such as the stomach content analysis, allow us to
      recognize differenttrophic groups, the importance of trophic levels and the
      interrelationships among species and other members ofthe community. In this
      investigation, we studied food habits, feeding variation and trophic
      relationships of thefishes present in streams of the Corral de San Luis drainage,
      Tubara, Atlantico Department, a part of the lowerMagdalena River Basin in
      Colombian Caribbean. Fish samples of Awaous banana, Agonostomus
      monticola,Andinoacara latifrons, Hyphessobrycon proteus, Poecilia gillii,
      Gobiomorus dormitor and Synbranchus marmoratuswere obtained using a seine (2x5 m,
      mesh 0.5 cm), from November 2012 to October 2013. To analyzetheir stomach
      contents, we used numeric (% N), volumetric (% V) and frequency of occurrence (%
      FO) methods,an emptiness coefficient (C.V), index of food item importance (I.A).
      Besides, physical and chemical habitatparameters were recorded on site.
      Information obtained was processed using multivariate statistical
      analysis,ecological indices, and null models: canonical correspondence analysis
      (CCA), principal component analysis(PCA), trophic niche amplitude (Shannon-Weaver
      H') and trophic overlap (Morisita-Horn). We observed significantdifferences on
      food resources consumption (K-W= 20.86; p<0.05) among the studied species.
      Theywere classified according to their food habits as omnivores with a tendency
      towards insectivory (A. monticolaH'0.60; A. latifrons H'0.43), herbivores with a
      tendency towards the consumption of algae (A. banana H'0.50;P. gillii H'0.54) and
      carnivores with a tendency towards insectivory (H. proteus H'0.23); benthic
      invertebratesand microalgae were found the most important food sources. A total
      of 65 food items were identified in thisstudy: 21 for A. banana (2 unique, 19
      shared), 40 for A. monticola (21 unique, 19 shared), 19 for A. latifrons
      (5unique, 14 shared), 6 for H. proteus (1 unique, 5 shared) and P. gillii with 28
      (4 unique, 24 shared). The canonicalcorrespondence analysis showed that water
      conductivity, salinity and pH were the variables that directlyinfluenced fish
      community structure at the sampled sites. The null model analyses showed that the
      group offishes was significantly segregated (p= 0.001) along the trophic axis,
      with respect to shared food items, and thatthe segregation was not influenced or
      generated by competition. The Morisita-Horn index showed false trophicoverlap
      (similarity of about 80 %) between A. banana and P. gillii. The first component
      of the PCA analysis wasexplained mainly by phytoplankton, and component two was
      correlated with items of animal origin. The fishesassociated with PC1 were P.
      gillii and A. banana, with high ingestion values of microalgae. PC2 was
      explainedby A. monticola with high numbers of food items of animal origin. The
      group of fishes studied behaved as anassemblage; given that the trophic
      interrelationships showed false trophic overlap, and that they did not excludeone
      another from the ecosystems, but instead, used different food resources and
      different physical spaces withintheir habitat.

PMID- 29451766
TI  - Endophytic fungi from tropical ethnoveterinary plants and their antibacterial
      efficacy against Pasteurella multocida Capsular Type A strain.
AB  - Pasteurella multocida is an important veterinary pathogen causing infections in
      animals and birds.Nowadays, different reports have described the severity of
      infections, increasing resistance of micro-organismsto antibiotics, and the
      contribution of ethnoveterinary practices towards the treatment of various
      ailments ofanimals. The aim of the present study was to investigate the
      antibacterial efficacy of the ethanolic extracts ofendophytic fungi against P.
      multocida Capsular Type A strains. A total of six endophytic fungi were
      isolatedfrom two tropical ethnoveterinary plants: Garcinia xanthochymus H. and
      Polygonum chinense L. The ethanolicextracts of the endophytic fungi were
      subjected to in vitro antimicrobial activity by the well diffusion
      method.Besides, we evaluated the treatment of mice with the potent fungal extract
      and observed the effects in differentorgans under electron microscopy. Our
      results showed that four fungi had antimicrobial activity against theselected
      pathogen. The best antibacterial activity was showed by the extract of the
      endophytic fungi, Glomerellamagna isolated from G. xanthochymus, with a minimum
      inhibitory concentration of 46.9 MUg/mL and minimumbactericidal concentration of
      750 MUg/mL. Treatment of mice with the potent fungal extract caused a
      considerableinhibitory effect on the pathogen growth in vital organs, results
      that was also confirmed by histopathologicalstudies made by scanning electron
      microscopy. The present findings indicated that the endophytic fungi G.magna has
      the potential to provide an effective treatment against infections caused by
      Pasteurella multocida.However, the isolation of bioactive components needs
      further investigation.

PMID- 29451767
TI  - [Spatial patterns in communities of aquatic macroinvertebrates of Argentinean
      Puna].
AB  - Spatial patterns in communities of aquatic macroinvertebrates of Argentinean
      Puna. The macroinvertebratesare a vital component of freshwater ecosystems as
      they contribute to the process of organic matter whileserving as food for other
      organisms such as fish and amphibians. Unfortunately, the knowledge of the
      aquaticdiversity is poor in the high Andean systems (between 3 200 and 5 200
      m.a.s.l. and rainfall below 300 mm peryear), especially in the Argentinean
      peatbogs, a fact which has made difficult the interpretation of spatial
      patternson a regional scale. The present study aimed to describe the composition
      of aquatic macroinvertebrates in sevenpeatbogs in the Argentinean Puna, and to
      analyze for the first time their spatial patterns. For this, we studiedthe
      relationship of these organisms with the environment, and obtained information
      about the surrounding vegetationand water physico-chemical characteristics. A
      total of 3 131 specimens of aquatic macroinvertebrateswere collected,
      representing 25 taxa belonging to 22 families and 24 genera. In addition, 62
      species of vascularplants were recorded, belonging to 20 families. The most
      abundant life form were the tufted grasses, followedby cushions. By using an NMDS
      (Non-Metrical Multidimensional Scaling) statistical analysis, the samplingsites
      were ordered in each peatbog as follows. The peatbogs located furthest West and
      South with higher watertemperature were grouped on axis 1, whereas those with
      higher conductivity, whole water dissolved solidsand salt concentration were
      grouped on axis 2. The water temperature was higher than air temperature at
      alltimes, and we found no association between temperature and altitude. The
      altitude had no correlation with theabundance of macroinvertebrates or with plant
      richness. Life forms such as scattered graminoids, trailing andprostrate herbs
      (in many cases they get into the channel) and aquatic plants were more abundant
      in peatbogs 4,5 and 7 and they had a correlation with some macroinvertebrates
      belonging to functional trophic groups suchas filter-collectors, collectors and
      scrapers. Finally, conductivity, whole dissolved solids and salt concentrationhad
      their highest value in peatbog 6, where Bivalvia (filter-collector) and Hyalella
      (collector) were also found.The results obtained attest that these
      macroinvertebrates displayed diversity and composition spatial patterns,the most
      important feature being their relationship with the surrounding vegetation, and
      to a lesser extent, withthe physical and chemical traits of water in seven
      fertile lowlands in the Argentinean Puna.

PMID- 29451768
TI  - Effects of habitat management on different feeding guilds of herbivorous insects
      in cacao agroforestry systems.
AB  - Human pressure on natural habitats increases the importance of agroforests for
      biodiversity conservation.The objective of this study was to evaluate the role of
      cacao traditional cultivation system (CTCS) onthe conservation of the herbivorous
      insect community when compared with a monodominant rubber agroforest,a type of
      agricultural system for cacao cultivation. The insects were sampled in three
      habitats in SoutheasternBahia, Brazil: native forests, CTCS and rubber
      agroforests. In each habitat, 18 plots of 10 m2 were established,and the
      structural measures were collected and herbivorous insects were sampled with a
      Malaise/window trap.The diversity of folivorous decreased with the simplification
      of vegetation structure, but species compositionwas similar among habitats. In
      addition to a decrease in the availability of resources in monodominant
      rubberagroforests, the latex present in these systems have limited the occurrence
      of species that cannot circumventlatex toxicity. The diversity of sap-sucking
      insects was similar among habitats, but species composition wassimilar only in
      the CTCS and native forest, and it was different in the rubber agroforest. We
      observed turnoverand a higher frequency of individuals of the family Psyllidae in
      the rubber agroforest. The biology and behaviorof Psyllids and absence of natural
      enemies enable their diversity to increase when they are adapted to a new host.We
      observed a shift in the composition of xylophagous insects in the rubber
      agroforest compared to that in otherhabitats. Moreover, this agroforest has low
      species richness, but high individual abundance. Latex extraction islikely an
      important additional source of volatile compounds discharged into the
      environment, and it increasesthe attraction and recruitment of coleoborers to
      these sites. We concluded that CTCS has an herbivorous insectcommunity with a
      structure similar to the community found in native forests of the region, and
      they present amore interesting conservation strategy when compared to rubber
      agroforests. We also emphasized the potentialrisk of local pest outbreaks in
      rubber agroforests for both the rubber and associated cacao trees.

PMID- 29451769
TI  - Glutathione-S-transferase production in earthworm (Annelida: Eudrilidae) as a
      tool for heavy metal pollution assessment in abattoir soil.
AB  - The use of direct response of animals to environmental challenges by production
      of biomarkers isa better tool to assess environmental pollution than the
      conventional methods. This study aimed to measureGlutathione-S-transferase (GST)
      in earthworms as tools for assessing heavy metal pollution in abattoir soil.Five
      (5) replicates each of earthworm species (Libyodrilus violaceous, Eudrilus
      eugeniae and Alma millsoni),soil and rumen waste samples were collected from
      three (3) abattoir sites (Lafenwa, Gbonogun and Madojutimiabattoirs), and a
      control site located within Federal University of Agriculture Abeokuta, beside an
      undisturbedstream with no rumen waste. Heavy metal (Cu, Zn, Pb, Cd, Co, Cr, Ni
      and Mn) concentrations in rumen waste,abattoir soils and earthworm tissues were
      determined using Atomic Absorption Spectrophotometer. The pH andorganic matter
      (OM) concentrations of the rumen waste and abattoir soils were determined by
      standard methods.GST activities in the earthworm tissues were determined through
      the conjugation of 1 mM reduced glutathione(GSH) with 1 mM 1-chloro-2,4
      dinitrobenzene (CDNB). The rumen waste recorded significantly higher (p <=0.05) %
      OM, heavy metal concentrations and pH level than in their respective abattoir
      soils. The mean heavymetal concentrations of Cu, Zn, Pb, Cd and Mn were highest
      in the tissue of earthworm species obtained fromLafenwa abattoir. A significantly
      (p <= 0.05) higher GST activities were recorded in the tissue of earthwormspecies
      obtained from Lafenwa and Gbonogun abattoirs. Libyodrilous violaceus obtained
      from Lafenwa abattoirrecorded the highest GST activity (8.47+/-1.39) in their
      tissue followed by the ones from Gbonogun abattoir(8.21+/-0.85). A significant (p
      <= 0.05) positive correlations was observed between GST activities in
      earthwormtissues and heavy metal concentrations. GST activities can therefore be
      used to assess the level of heavy metalpollution in abattoir soils.

PMID- 29451770
TI  - Thermodynamic and Kinetic Effects in the Crystallization of Metal-Organic
      Frameworks.
AB  - The evolution of metal-organic frameworks (MOFs) has been one of the most
      exciting aspects of materials chemistry over the last 20 years. In this Account,
      we discuss the development during this period in our understanding of the factors
      that control the crystallization of MOFs from solution. Both classical porous
      MOFs and dense MOF phases are considered. This is an opportune time at which to
      examine this complex area because the experimental tools now available to
      interrogate crystallization processes have matured significantly in the last 5
      years, particularly with the use of in situ synchrotron X-ray diffraction. There
      have also been impressive developments in the use of density functional theory
      (DFT) to treat not only the energies of very complex structures but also their
      entropies. This is particularly important in MOF frameworks because of their much
      greater flexibility compared with inorganic structures such as zeolites. The
      first section of the Account describes how early empirical observations on the
      crystallization of dense MOFs pointed to a strong degree of thermodynamic
      control, with both enthalpic and entropic factors playing important roles. For
      example, reactions at higher temperatures tend to lead to denser structures with
      higher degrees of framework connectivity and lower levels of solvation, and
      polymorphs tend to form according to their thermodynamic stabilities. In the case
      of metal tartrates, these trends have been validated by calorimetric studies. It
      has been clear for more than a decade, however, that certain phases crystallize
      under kinetic control, especially when a change in conformation of the ligand or
      coordination around a metal center might be necessary to form the
      thermodynamically preferred product. We describe how this can lead to time
      dependent crystallization processes that evolve according to the Ostwald rule of
      stages and can be observed by in situ methods. We then consider the
      crystallization of porous MOFs, which presents additional challenges because of
      solvation effects. In spite of these problems, much has been learned about the
      energetics of the underlying frameworks, where the relationship between porosity
      and stability initially seemed to mirror the behavior of zeolites, with more
      porous structures being less stable. Recently, however, this simple relationship
      has had to be reconsidered with the emergence of some very flexible structures
      wherein the open structures are more stable than their denser analogues at finite
      temperatures because of their large vibrational entropies. In the final section
      we describe how the concepts developed in the MOF work have been extended into
      the closely related area of hybrid organic-inorganic perovskites. We describe
      recent studies on polymorphism in hybrid perovskites, which is amenable to total
      free energy calculations using a combination of DFT and lattice dynamics methods.

PMID- 29451771
TI  - Structural Transformation of Wireframe DNA Origami via DNA Polymerase Assisted
      Gap-Filling.
AB  - The programmability of DNA enables constructing nanostructures with almost any
      arbitrary shape, which can be decorated with many functional materials. Moreover,
      dynamic structures can be realized such as molecular motors and walkers. In this
      work, we have explored the possibility to synthesize the complementary sequences
      to single-stranded gap regions in the DNA origami scaffold cost effectively by a
      DNA polymerase rather than by a DNA synthesizer. For this purpose, four different
      wireframe DNA origami structures were designed to have single-stranded gap
      regions. This reduced the number of staple strands needed to determine the shape
      and size of the final structure after gap filling. For this, several DNA
      polymerases and single-stranded binding (SSB) proteins were tested, with T4 DNA
      polymerase being the best fit. The structures could be folded in as little as 6
      min, and the subsequent optimized gap-filling reaction was completed in less than
      3 min. The introduction of flexible gap regions results in fully collapsed or
      partially bent structures due to entropic spring effects. Finally, we
      demonstrated structural transformations of such deformed wireframe DNA origami
      structures with DNA polymerases including the expansion of collapsed structures
      and the straightening of curved tubes. We anticipate that this approach will
      become a powerful tool to build DNA wireframe structures more material
      efficiently, and to quickly prototype and test new wireframe designs that can be
      expanded, rigidified, or mechanically switched. Mechanical force generation and
      structural transitions will enable applications in structural DNA nanotechnology,
      plasmonics, or single-molecule biophysics.

PMID- 29451772
TI  - Ultraflexible and High-Performance Multilayer Transparent Electrode Based on
      ZnO/Ag/CuSCN.
AB  - Driven by huge demand for flexible optoelectronic devices, high-performance
      flexible transparent electrodes are continuously sought. In this work, a flexible
      multilayer transparent electrode with the structure of ZnO/Ag/CuSCN (ZAC) is
      engineered, featuring inorganic solution-processed cuprous thiocyanate (CuSCN) as
      a hole-transport antireflection coating. The ZAC electrode exhibits an average
      transmittance of 94% (discounting the substrate) in the visible range, a sheet
      resistance ( Rsh) of 9.7 Omega/sq, a high mechanical flexibility without Rsh
      variation after bending 10 000 times, a long-term stability of 400 days in
      ambient environment, and a scalable fabrication process. Moreover, spontaneously
      formed nanobulges are integrated into ZAC electrode, and light outcoupling is
      significantly improved. As a result, when applied into super yellow-based
      flexible organic light-emitting diode, the ZAC electrode provides a high-current
      efficiency of 23.4 cd/A and excellent device flexibility. These results suggest
      that multilayer thin films with ingenious material design and engineering can
      serve as a promising flexible transparent electrode for optoelectronic
      applications.

PMID- 29451773
TI  - Surface Cation Segregation and Chromium Deposition on the Double-Perovskite Oxide
      PrBaCo2O5+delta.
AB  - The surface chemistry and the Cr tolerance ability of oxygen electrodes play a
      vital role in the performance and long-term stability of solid oxide cells
      (SOCs). In this paper, the surface cation segregations on the double-perovskite
      oxide PrBaCo2O5+delta (PBCO) and its relationship with Cr deposition are
      reported. During high-temperature annealing in an O2 atmosphere, the elements Ba
      and Co diffuse out of the lattice and form many BaO and Co3O4 precipitates on the
      surface, mainly located at grain boundaries. In the presence of volatile Cr
      species, the observation of BaCrO4, but not CoCr2O4, on a segregated PBCO surface
      reveals that the Cr deposition preferentially takes place on segregated BaO
      rather than on Co3O4 precipitates. Our results show that segregated BaO
      precipitates are very active toward Cr vapor and PBCO is not a Cr-tolerant oxygen
      electrode for SOCs operating at high temperatures, despite its superior
      electrochemical performance.

PMID- 29451774
TI  - Organic Semiconducting Photoacoustic Nanodroplets for Laser-Activatable
      Ultrasound Imaging and Combinational Cancer Therapy.
AB  - Combination of photoacoustic (PA) and ultrasound (US) imaging offers high spatial
      resolution images with deep tissue penetration, which shows great potential in
      applications in medical imaging. Development of PA/US dual-contrast agents with
      high contrast and excellent biocompatibility is of great interest. Herein, an
      organic semiconducting photoacoustic nanodroplet, PS-PDI-PAnD, is developed by
      stabilizing low-boiling-point perfluorocarbon (PFC) droplet with a photoabsorber
      and photoacoustic agent of perylene diimide (PDI) molecules and coencapsulating
      the droplet with photosensitizers of ZnF16Pc molecules. Upon irradiation, the PDI
      acts as an efficient photoabsorber to trigger the liquid-to-gas phase transition
      of the PFC, resulting in dual-modal PA/US imaging contrast as well as
      photothermal heating. On the other hand, PFC can serve as an O2 reservoir to
      overcome the hypoxia-associated resistance in cancer therapies, especially in
      photodynamic therapy. The encapsulated photosensitizers will benefit from the
      sustained oxygen release from the PFC, leading to promoted photodynamic efficacy
      regardless of pre-existing hypoxia in the tumors. When intravenously injected
      into tumor-bearing mice, the PS-PDI-PAnDs show a high tumor accumulation via EPR
      effect. With a single 671 nm laser irradiation, the PS-PDI-PAnDs exhibit a dual
      modal PA/US imaging-guided synergistic photothermal and oxygen self-enriched
      photodynamic treatment, resulting in complete tumor eradication and minimal side
      effects. The PS-PDI-PAnDs represents a type of PFC nanodroplets for synergistic
      PDT/PTT treatment upon a single laser irradiation, which is expected to hold
      great potential in the clinical translation in dual-modal PA/US imaging-guided
      combinational cancer therapy.

PMID- 29451775
TI  - Fluorescence Imaging of Huntingtin mRNA Knockdown.
AB  - Huntington's disease (HD) is an autosomal-dominant neurodegenerative genetic
      disorder caused by CAG repeat expansion in exon 1 of the HTT gene. Expression of
      the mutant gene results in the production of a neurotoxic polyglutamine (polyQ)
      expanded huntingtin (Htt) protein. Clinical trials of knockdown therapy of mutant
      polyglutamine-encoding HTT mRNA in Huntington's disease (HD) have begun. To
      measure HTT mRNA knockdown effectiveness in human cells, we utilized a
      fluorescent hybridization imaging agent specific to the region encompassing the
      human HTT mRNA initiation codon. We designed, synthesized, purified, and
      characterized Cal560-spacer-peptide nucleic acid (PNA)-spacer-IGF1 tetrapeptides.
      The human HTT PNA 12mer complement was CATGGCGGTCTC, while the rat htt equivalent
      12mer contained the sequence CATGaCGGcCTC, with two bases differing from the
      human sequence. The cyclized IGF1 tetrapeptide fragment d(CSKC) that promotes
      IGF1 receptor-mediated endocytosis was bonded to the C-terminus. We tested the
      reliability of HTT mRNA imaging with Cal560-spacer-peptide nucleic acid (PNA)
      spacer-IGF1 tetrapeptides in human embryonic kidney (HEK) 293T cells that express
      endogenous HTT and IGF1 receptor. By qPCR, we quantitated HTT mRNA in HEK293T
      cells with and without HTT mRNA knockdown by three different siRNAs. By confocal
      fluorescence imaging, we quantitated the accumulation of fluorescent HTT
      hybridization agent in the same cells. A rat homologue differing from the human
      sequence by two bases showed negligible fluorescence. qPCR indicated 86 +/- 5%
      knockdown of HTT mRNA by the most effective siRNA. Similarly, Cal560- HTT PNA
      peptide fluorescence intensity indicated 69 +/- 6% reduction in HTT mRNA. We
      concluded that the fluorescence hybridization method correlates with the
      established qPCR method for quantitating HTT mRNA knockdown by siRNA in HEK293T
      cells, with a Pearson correlation coefficient of 0.865 for all three siRNA
      sequences. These results will enable real time imaging and quantitation of HTT
      mRNA in animal models of HD.

PMID- 29451776
TI  - Short-Term Pulmonary Toxicity Assessment of Pre- and Post-incinerated
      Organomodified Nanoclay in Mice.
AB  - Organomodified nanoclays (ONCs) are increasingly used as filler materials to
      improve nanocomposite strength, wettability, flammability, and durability.
      However, pulmonary risks associated with exposure along their chemical lifecycle
      are unknown. This study's objective was to compare pre- and post-incinerated
      forms of uncoated and organomodified nanoclays for potential pulmonary
      inflammation, toxicity, and systemic blood response. Mice were exposed via
      aspiration to low (30 MUg) and high (300 MUg) doses of preincinerated uncoated
      montmorillonite nanoclay (CloisNa), ONC (Clois30B), their respective incinerated
      forms (I-CloisNa and I-Clois30B), and crystalline silica (CS). Lung and blood
      tissues were collected at days 1, 7, and 28 to compare toxicity and inflammation
      indices. Well-dispersed CloisNa caused a robust inflammatory response
      characterized by neutrophils, macrophages, and particle-laden granulomas.
      Alternatively, Clois30B, I-Clois30B, and CS high-dose exposures elicited a low
      grade, persistent inflammatory response. High-dose Clois30B exposure exhibited
      moderate increases in lung damage markers and a delayed macrophage recruitment
      cytokine signature peaking at day 7 followed by a fibrotic tissue signature at
      day 28, similar to CloisNa. I-CloisNa exhibited acute, transient inflammation
      with quick recovery. Conversely, high-dose I-Clois30B caused a weak initial
      inflammatory signal but showed comparable pro-inflammatory signaling to CS at day
      28. The data demonstrate that ONC pulmonary toxicity and inflammatory potential
      relies on coating presence and incineration status in that coated and incinerated
      nanoclay exhibited less inflammation and granuloma formation than pristine
      montmorillonite. High doses of both pre- and post-incinerated ONC, with different
      surface morphologies, may harbor potential pulmonary health hazards over long
      term occupational exposures.

PMID- 29451778
TI  - Rapid-Forming and Self-Healing Agarose-Based Hydrogels for Tissue Adhesives and
      Potential Wound Dressings.
AB  - To meet the progressive requirements of advanced engineering materials with
      superior physicochemical performances, self-healing and injectable hydrogels (AD
      hydrogels) based on agarose with pH-response were prepared through dynamic
      covalent Schiff-base linkages by simply mixing nontoxic agarose-ethylenediamine
      conjugate (AG-NH2) and dialdehyde-functionalized polyethylene glycol (DF-PEG)
      solutions. The self-healing and injectable capabilities of the hydrogels without
      any external stimulus are ascribed to dynamic covalent Schiff-base linkages
      between the aldehyde groups of DF-PEG and amine groups on AG-NH2 backbone. It is
      demonstrated that the AD hydrogels possess interconnected porous morphologies,
      rapid gelation time, excellent deformability, and good mechanical strength. The
      incorporated Schiff's base imparts the hydrogels to the remarkable tissue
      adhesiveness. In vivo hemostatic tests on rabbit liver demonstrate that the
      hydrogels are able to stanch the severe trauma effectively. Compared with the
      conventional gauze treatment, the total amount of bleeding sharply declined to be
      (0.19 +/- 0.03) g, and hemostasis time was strikingly shorter than 10 s after
      treating with AD hydrogels. In summary, the self-healing ability,
      cytocompatibility, and adhesion characteristic of the pH-responsive hydrogels
      make them promising candidates for long-lived wound dressings in critical
      situations.

PMID- 29451777
TI  - Filomicelles Deliver a Chemo-Differentiation Combination of Paclitaxel and
      Retinoic Acid That Durably Represses Carcinomas in Liver to Prolong Survival.
AB  - Drug resistance and relapse is common in cancer treatments with
      chemotherapeutics, and while drug combinations with naturally occurring,
      differentiation-inducing retinoic acid (RA) provide remission-free cures for one
      type of liquid tumor, solid tumors present major problems for delivery. Here,
      inspired by filoviruses that can be microns in length, flexible filomicelles that
      self-assemble from an amphiphilic block copolymer (PEG-PCL) are shown to
      effectively deliver RA and paclitaxel (TAX) to several solid tumor models,
      particularly in the liver. These hydrophobic compounds synergistically load into
      the cores of the elongated micelles, and the coloaded micelles prove most
      effective at causing cell death, ploidy, and durable regression of tumors
      compared to free drugs or to separately loaded drugs. RA-TAX filomicelles also
      reduce mortality of human lung or liver derived cancers engrafted at liver,
      intraperitoneal, and subcutaneous sites in immunodeficient mice. In vitro studies
      show that the dual drug micelles effectively suppress proliferation while
      upregulating a generic differentiation marker. The results highlight the potency
      of dual-loaded filomicelles in killing cancer cells or else driving their
      differentiation away from growth.

PMID- 29451779
TI  - Real-Time Intrinsic Fluorescence Visualization and Sizing of Proteins and Protein
      Complexes in Microfluidic Devices.
AB  - Optical detection has become a convenient and scalable approach to read out
      information from microfluidic systems. For the study of many key biomolecules,
      however, including peptides and proteins, which have low fluorescence emission
      efficiencies at visible wavelengths, this approach typically requires labeling of
      the species of interest with extrinsic fluorophores to enhance the optical signal
      obtained - a process which can be time-consuming, requires purification steps,
      and has the propensity to perturb the behavior of the systems under study due to
      interactions between the labels and the analyte molecules. As such, the
      exploitation of the intrinsic fluorescence of protein molecules in the UV range
      of the electromagnetic spectrum is an attractive path to allow the study of
      unlabeled proteins. However, direct visualization using 280 nm excitation in
      microfluidic devices has to date commonly required the use of coherent sources
      with frequency multipliers and devices fabricated out of materials that are
      incompatible with soft lithography techniques. Here, we have developed a simple,
      robust, and cost-effective 280 nm LED platform that allows real-time
      visualization of intrinsic fluorescence from both unlabeled proteins and protein
      complexes in polydimethylsiloxane microfluidic channels fabricated through soft
      lithography. Using this platform, we demonstrate intrinsic fluorescence
      visualization of proteins at nanomolar concentrations on chip and combine
      visualization with micron-scale diffusional sizing to measure the hydrodynamic
      radii of individual proteins and protein complexes under their native conditions
      in solution in a label-free manner.

PMID- 29451781
TI  - Multiple SNPs Detection Based on Lateral Flow Assay for Phenylketonuria
      Diagnostic.
AB  - Single nucleotide polymorphisms (SNPs) are closely related to genetic diseases,
      but current SNP detection methods, such as DNA microarrays that include tedious
      procedures and expensive, sophisticated instruments, are unable to perform rapid
      SNPs detection in clinical practice, especially for those multiple SNPs related
      to genetic diseases. In this study, we report a sensitive, low cost, and easy-to
      use point-of-care testing (POCT) system formed by combining amplification
      refractory mutation system (ARMS) polymerase chain reaction with gold magnetic
      nanoparticles (GMNPs) and lateral flow assay (LFA) noted as the ARMS-LFA system,
      which allow us to use a uniform condition for multiple SNPs detection
      simultaneously. The genotyping results can be explained by a magnetic reader
      automatically or through visual interpretation according to the captured GMNPs
      probes on the test and control lines of the LFA device. The high sensitivity (the
      detection limit of 0.04 pg/MUL with plasmid) and specificity of this testing
      system were found through genotyping seven pathogenic SNPs in phenylalanine
      hydroxylase gene ( PAH, the etiological factor of phenylketonuria). This system
      can also be applied in DNA quantification with a linear range from 0.02 to 2
      pg/MUL of plasmid. Furthermore, this ARMS-LFA system was applied to clinical
      trials for screening the seven pathogenic SNPs in PAH of 23 families including 69
      individuals. The concordance rate of the genotyping results detected by the ARMS
      LFA system was up to 97.8% compared with the DNA sequencing results. This method
      is a very promising POCT in the detection of multiple SNPs caused by genetic
      diseases.

PMID- 29451782
TI  - Molecular Recognition with Resorcin[4]arene Cavitands: Switching, Halogen-Bonded
      Capsules, and Enantioselective Complexation.
AB  - The development of synthetic host-guest chemistry to investigate and quantify
      weak, non-covalent interactions has been key to unraveling the complexity of
      molecular recognition in chemical and biological systems. Macrocycles have shown
      great utility in the design of receptors, enabling the development of highly
      preorganized structures. Among macrocycles, resorcin[4]arene-based cavitands have
      become privileged scaffolds due to their synthetic tunability, which allows
      access to structures with precisely defined geometries, as well as receptors that
      display conformational switching between two distinct states with a large
      difference in guest-binding properties. Here, we highlight three case studies
      demonstrating redox- and photoredox-controlled switching of molecular recognition
      properties, the formation of guest-binding supramolecular capsules based solely
      on halogen-bonding interactions, and enantioselective encapsulation of chiral,
      substituted cyclohexanes by enantiopure cage compounds as a result of perfect
      shape complementarity, dispersion interactions, and halogen bonding. The high
      geometrical and conformational control that can be achieved with resorcin[4]arene
      derived host systems will continue to be a powerful resource in future molecular
      recognition studies.

PMID- 29451780
TI  - Using in Vitro Evolution and Whole Genome Analysis To Discover Next Generation
      Targets for Antimalarial Drug Discovery.
AB  - Although many new anti-infectives have been discovered and developed solely using
      phenotypic cellular screening and assay optimization, most researchers recognize
      that structure-guided drug design is more practical and less costly. In addition,
      a greater chemical space can be interrogated with structure-guided drug design.
      The practicality of structure-guided drug design has launched a search for the
      targets of compounds discovered in phenotypic screens. One method that has been
      used extensively in malaria parasites for target discovery and chemical
      validation is in vitro evolution and whole genome analysis (IVIEWGA). Here, small
      molecules from phenotypic screens with demonstrated antiparasitic activity are
      used in genome-based target discovery methods. In this Review, we discuss the
      newest, most promising druggable targets discovered or further validated by
      evolution-based methods, as well as some exceptions.

PMID- 29451783
TI  - SuFEx Click Chemistry Enabled Late-Stage Drug Functionalization.
AB  - Sulfur(VI) Fluoride Exchange (SuFEx) is a new family of click chemistry
      transformations which relies on readily available materials to produce compounds
      bearing the SVI-F motif. The potential of SuFEx in drug discovery has just
      started to be explored. We report the first method of SuFEx chemistry for the
      conversion of phenolic compounds to their respective arylfluorosulfate
      derivatives in situ in 96-well plates. This method is compatible with automated
      synthesis and screening to quickly assess the biological activities of the in
      situ generated, crude products. Using this method, we perform late-stage
      functionalization of a panel of known anticancer drugs to generate the
      corresponding arylfluorosulfates. These in situ generated arylfluorosulfates are
      directly tested in a cancer-cell growth inhibition assay in parallel with their
      phenolic precursors. We discover three arylfluorosulfates that exhibit improved
      anticancer cell proliferation activities compared to their phenol precursors.
      Among these three compounds, the fluorosulfate derivative of Fulvestrant
      possesses significantly enhanced activity to down-regulate estrogen receptor (ER)
      expression in ER+ breast cancer cell line MCF-7 and the fluorosulfate derivative
      of Combretastatin A4-a general anticancer drug currently being evaluated under
      clinical trials-exhibits a 70-fold increase in potency in the drug resistant
      colon cancer cell line HT-29.

PMID- 29451785
TI  - Structure-Function Evaluation of Imidazopyridine Derivatives Selective for delta
      Subunit-Containing gamma-Aminobutyric Acid Type A (GABAA) Receptors.
AB  - delta-Selective compounds 1 and 2 (DS1, compound 22; DS2, compound 16) were
      introduced as functionally selective modulators of delta-containing GABA type A
      receptors (GABAAR). In our hands, [3H]EBOB-binding experiments with recombinant
      GABAAR and compound 22 showed no proof of delta-selectivity, although there was a
      minimally higher preference for the alpha4beta3delta and alpha6beta2/3delta
      receptors with respect to potency. In order to delineate the structural
      determinants of delta preferences, we synthesized 25 derivatives of DS1 and DS2,
      and investigated their structure-activity relationships (SAR). Four of our
      derivatives showed selectivity for alpha6beta3delta receptors (29, 38, 39, and
      41). For all of them, the major factors that distinguished them from compound 22
      were variations at the para-positions of their benzamide groups. However, two
      compounds (29 and 39), when tested in the presence of GABA, revealed effects at
      several additional GABAAR. The newly synthesized compounds will still serve as
      useful tools to investigate alpha6beta3delta receptors.

PMID- 29451784
TI  - Alteration of Crop Yield and Quality of Wheat upon Exposure to Silver
      Nanoparticles in a Life Cycle Study.
AB  - As a result of the rapid development of nanotechnology, metal-based nanoparticles
      (NPs) are inadvertently released into the environment and may pose a potential
      threat to the ecosystem. However, information for food quality and safety in NP
      treated crops is limited. In the present study, wheat ( Triticum aestivum L.) was
      grown in different concentrations of Ag-NP-amended soil (20, 200, and 2000 mg kg
      1) for 4 months. At harvest, physiological parameters, Ag and micronutrient (Fe,
      Cu, and Zn) contents, and amino acid and total protein contents were measured.
      Results showed that, with increasing the exposure doses, Ag NPs exhibited severe
      phytotoxicity, including lower biomass, shorter plant height, and lower grain
      weight. Ag accumulation in roots was significantly higher than that in shoots and
      grains. Decreases in the content of micronutrients (Fe, Cu, and Zn) in Ag-NP
      treated grains suggested low crop quality. The results of amino acid and protein
      contents in Ag-NP-treated wheat grains indicated that Ag NPs indeed altered the
      nutrient contents in the edible portion. In the amino acid profile, the presence
      of Ag NPs significantly decreased the contents of arginine and histidine by 13.0
      and 11.8%, respectively. In summary, the effects of metal-based NPs on the edible
      portion of crops should be taken into account in the evaluation of nanotoxicity
      to terrestrial plants. Moreover, investigation of the potential impacts of NP
      caused nutrient alterations on human health could further our understandings on
      NP-induced phytotoxicity.

PMID- 29451786
TI  - The Catalytic Reaction of Nitroxides with Peroxyl Radicals and Its Relevance to
      Their Cytoprotective Properties.
AB  - Sterically-hindered nitroxides such as 2,2,6,6-tetramethylpiperidin- N-oxyl
      (TEMPO) have long been ascribed antioxidant activity that is thought to underlie
      their chemopreventive and anti-aging properties. However, the most commonly
      invoked reactions in this context-combination with an alkyl radical to give a
      redox inactive alkoxyamine or catalysis of superoxide dismutation-are unlikely to
      be relevant under (most) physiological conditions. Herein, we characterize the
      kinetics and mechanisms of the reactions of TEMPO, as well as an N-arylnitroxide
      and an N, N-diarylnitroxide, with alkylperoxyl radicals, the propagating species
      in lipid peroxidation. In each of aqueous solution and lipid bilayers, they are
      found to be significantly more reactive than Vitamin E, Nature's premier radical
      trapping antioxidant (RTA). Inhibited autoxidations of THF in aqueous buffers
      reveal that nitroxides reduce peroxyl radicals by electron transfer with rate
      constants ( k ~ 106 to >107 M-1 s-1) that correlate with the standard potentials
      of the nitroxides ( E degrees  ~ 0.75-0.95 V vs NHE) and that this activity is
      catalytic in nitroxide. Regeneration of the nitroxide occurs by a two-step
      process involving hydride transfer from the substrate to the nitroxide-derived
      oxoammonium ion followed by H-atom transfer from the resultant hydroxylamine to a
      peroxyl radical. This reactivity extends from aqueous solution to
      phosphatidylcholine liposomes, where added NADPH can be used as a hydride donor
      to promote nitroxide recycling, as well as to cell culture, where the nitroxides
      are shown to be potent inhibitors of lipid peroxidation-associated cell death
      (ferroptosis). These insights have enabled the identification of the most potent
      nitroxide RTA and anti-ferroptotic agent yet described: phenoxazine- N-oxyl.

PMID- 29451787
TI  - Effect of Methyl Substitution on the N-H...O Interaction in Complexes of Pyrrole
      with Water, Methanol, and Dimethyl Ether: Matrix Isolation Infrared Spectroscopy
      and ab Initio Computational Studies.
AB  - Hydrogen-bonded interactions of pyrrole with water and methanol have been studied
      using matrix isolation infrared spectroscopy and compared with the calculation
      performed on dimethyl ether. Computations carried out at MP2/aug-cc-pVDZ level of
      theory yielded two minima for the pyrrole-water and pyrrole-methanol complexes.
      The global and local minima correspond to the N-H...O and O-H...pi complexes,
      respectively, where the N-H group of pyrrole interacts with oxygen of
      water/methanol and O-H of water and methanol interacts with the pi cloud of
      pyrrole. Computations performed on the pyrrole-dimethyl ether gave only N-H...O
      type complex. From the experimental vibrational wavenumber shifts in the N-H
      stretching and N-H bending modes of pyrrole, as well as in the O-H stretching
      modes of water and methanol, the 1:1 N-H...O complexes were discerned. The
      strength of the N-H...O hydrogen bond and the corresponding shift in the N-H
      stretching vibrational wavenumbers increases in the order pyrrole-water < pyrrole
      methanol < pyrrole-dimethyl ether, where a proton is successively replaced by a
      methyl group. Apart from the 1:1 complexes, higher clusters of 2:1 and 1:2
      pyrrole-water and pyrrole-methanol complexes were also generated in N2 matrix.
      Atoms in molecules and natural bond orbital analyses were carried out at the
      MP2/aug-cc-pVDZ level to understand the nature of interaction in the 1:1 pyrrole
      water, pyrrole-methanol and pyrrole-dimethyl ether complexes.

PMID- 29451788
TI  - Systematic Evaluation of the Use of Human Plasma and Serum for Mass-Spectrometry
      Based Shotgun Proteomics.
AB  - Over the last two decades, EDTA-plasma has been used as the preferred sample
      matrix for human blood proteomic profiling. Serum has also been employed widely.
      Only a few studies have assessed the difference and relevance of the proteome
      profiles obtained from plasma samples, such as EDTA-plasma or lithium-heparin
      plasma, and serum. A more complete evaluation of the use of EDTA-plasma, heparin
      plasma, and serum would greatly expand the comprehensiveness of shotgun
      proteomics of blood samples. In this study, we evaluated the use of heparin
      plasma with respect to EDTA-plasma and serum to profile blood proteomes using a
      scalable automated proteomic pipeline (ASAP2). The use of plasma and serum for
      mass-spectrometry-based shotgun proteomics was first tested with commercial
      pooled samples. The proteome coverage consistency and the quantitative
      performance were compared. Furthermore, protein measurements in EDTA-plasma and
      heparin-plasma samples were comparatively studied using matched sample pairs from
      20 individuals from the Australian Imaging, Biomarkers and Lifestyle (AIBL)
      Study. We identified 442 proteins in common between EDTA-plasma and heparin
      plasma samples. Overall agreement of the relative protein quantification between
      the sample pairs demonstrated that shotgun proteomics using workflows such as the
      ASAP2 is suitable in analyzing heparin-plasma and that such sample type may be
      considered in large-scale clinical research studies. Moreover, the partial
      proteome coverage overlaps (e.g., ~70%) showed that measures from heparin-plasma
      could be complementary to those obtained from EDTA-plasma.

PMID- 29451789
TI  - Solution-Grown Sodium Bismuth Dichalcogenides: Toward Earth-Abundant,
      Biocompatible Semiconductors.
AB  - Many technologically relevant semiconductors contain toxic, heavily regulated
      (Cd, Pb, As), or relatively scarce (Li, In) elements and often require high
      manufacturing costs. We report a facile, general, low-temperature, and size
      tunable (4-28 nm) solution phase synthesis of ternary APnE2 semiconductors based
      on Earth-abundant and biocompatible elements (A = Na, Pn = Bi, E = S or Se). The
      observed experimental band gaps (1.20-1.45 eV) fall within the ideal range for
      solar cells. Computational investigation of the lowest energy superstructures
      that result from "coloring", caused by mixed cation sites present in their rock
      salt lattice, agrees with other better-known members of this family of materials.
      Our synthesis unlocks a new class of low cost and environmentally friendly
      ternary semiconductors that show properties of interest for applications in
      energy conversion.

PMID- 29451790
TI  - Copper(II) Chlorate Complexes: The Renaissance of a Forgotten and Misjudged
      Energetic Anion.
AB  - A convenient synthetic route toward new copper(II) chlorate complexes with
      potential use in modern advanced ignition or initiation systems is described.
      Obtained compounds were not only accurately characterized (XRD, IR, UV/Vis EA and
      DTA) but also investigated for their energetic character (sensitivities,
      initiation capability and laser ignition). The copper 4-aminotriazolyl chlorate
      complex showed excellent initiation of PETN, while also being thermally stable
      and safe to handle. Solid-state UV-Vis measurements were performed to get a
      possible insight toward the laser initiation mechanism. In contrast to
      expectations, the presented copper(II) chlorate energetic coordination compounds
      show manageable sensitivities that can be tamed or boosted by the appropriate
      choice of nitrogen-rich ligands.

PMID- 29451791
TI  - Correction to Eudesmane Sesquiterpenes from Verbesina lanata with Inhibitory
      Activity against Grapevine Downy Mildew.

PMID- 29451792
TI  - Vibronic Coupling Analysis of the Ligand-Centered Phosphorescence of Gas-Phase
      Gd(III) and Lu(III) 9-Oxophenalen-1-one Complexes.
AB  - The gas-phase laser-induced photoluminescence of cationic mononuclear gadolinium
      and lutetium complexes involving two 9-oxophenalen-1-one ligands is reported.
      Performing measurements at a temperature of 83 K enables us to resolve vibronic
      transitions. Via comparison to Franck-Condon computations, the main vibrational
      contributions to the ligand-centered phosphorescence are determined to involve
      rocking, wagging, and stretching of the 9-oxophenalen-1-one-lanthanoid
      coordination in the low-energy range, intraligand bending, and stretching in the
      medium- to high-energy range, rocking of the carbonyl and methine groups, and C-H
      stretching beyond. Whereas Franck-Condon calculations based on density-functional
      harmonic frequency computations reproduce the main features of the vibrationally
      resolved emission spectra, the absolute transition energies as determined by
      density functional theory are off by several thousand wavenumbers. This
      discrepancy is found to remain at higher computational levels. The relative
      energy of the Gd(III) and Lu(III) emission bands is only reproduced at the
      coupled-cluster singles and doubles level and beyond.

PMID- 29451793
TI  - Temporary Anion States of Ethene Interacting with Single Molecules of Methane,
      Ethane, and Water.
AB  - When an excess electron is added into the pi* orbital of ethene, the resulting
      anion decays by electron autodetachment; that is, it represents an electronic
      state referred to as a temporary anion or resonance state. Here, the influence of
      a cluster environment on the energy and lifetime of this state is investigated.
      The clusters considered are ethene...CH4, ethene...C2H6, and ethene...H2O. Most
      of these clusters are systematically constructed so that the solvent interacts
      with the pi system in a specific way, and are thus by construction not minima
      with respect to all intermolecular degrees of freedom. However, for water, in
      addition, a minimal energy structure is examined. Systematic variation of the
      solvent and solvation geometry allows us to identify trends regarding effects due
      to polarizability, excluded volume, and polarity of the solvent molecules. The
      resonance parameters of ethene and all temporary cluster anions are computed with
      the symmetry-adapted cluster-configuration interaction electronic structure
      method in combination with a complex absorbing potential. This method is well
      established for small to intermediate sized molecules. In addition to the study
      of the solvation effects themselves, the question of how many basis functions are
      needed on the closed-shell solvating unit is examined.

PMID- 29451794
TI  - ( S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate
      Receptor Ligands: Further Exploration of Bioisosteric Replacements and Structural
      and Biological Investigation.
AB  - Starting from 1-4 and 7 structural templates, analogues based on bioisosteric
      replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR
      analysis. Interesting binding properties at GluA2, GluK1, and GluK3 receptors
      were discovered. The requirements for GluK3 interaction were elucidated by
      determining the X-ray structures of the GluK3-LBD with 2 and 5c and by
      computational studies. Antinociceptive potential was demonstrated for GluK1
      partial agonist 3 and antagonist 7 (2 mg/kg ip).

PMID- 29451795
TI  - Physisorption of H2 on Fullerenes and the Solvation of C60 by Hydrogen Clusters
      at Finite Temperature: A Theoretical Assessment.
AB  - The interaction between hydrogen and carbonaceous nanostructures is of
      fundamental interest in various areas of physical chemistry. In this contribution
      we have revisited the physisorption of hydrogen molecules and H2 clusters on
      fullerenes, following a first-principles approach in which the interaction is
      quantitatively evaluated for the C20 system using high-level electronic structure
      methods. Relative to coupled cluster data at the level of single, double, and
      perturbative triple excitations taken as a benchmark, the results for
      rotationally averaged physisorbed H2 show a good performance of MP2 variants and
      symmetry-adapted perturbation theory, but significant deviations and basis set
      convergence issues are found for dispersion-corrected density functional theory.
      These electronic structure data are fitted to produce effective coarse-grained
      potentials for use in larger systems such as C60-H2. Using path-integral
      molecular dynamics, the potentials are also applied to parahydrogen clusters
      solvated around fullerenes, across the regime where the first solvation shell
      becomes complete and as a function of increasing temperature. For C60 our
      findings indicate a sensible dependence of the critical solvation size on the
      underlying potential. As the temperature is increased, a competition is found
      between the surface and radial expansions of the solvation shell, with one
      molecule popping away at intermediate temperatures but getting reinserted at even
      higher temperatures.

PMID- 29451796
TI  - Polyelectrolyte Complex Nanoparticles from Chitosan and Acylated Rapeseed
      Cruciferin Protein for Curcumin Delivery.
AB  - Curcumin is a polyphenol that exhibits several biological activities, but its low
      aqueous solubility results in low bioavailability. To improve curcumin
      bioavailability, this study has focused on developing a polyelectrolyte
      complexation method to form layer-by-layer assembled nanoparticles, for curcumin
      delivery, with positively charged chitosan (CS) and negatively charged acylated
      cruciferin (ACRU), a rapeseed globulin. Nanoparticles (NPs) were prepared from
      ACRU and CS (2:1) at pH 5.7. Three samples with weight of 5%, 10%, and 15% of
      curcumin, respectively, in ACRU/CS carrier were prepared. To verify the stability
      of the NPs, encapsulation efficiency and size of the 5% Cur-ACRU/CS NPs were
      determined at intervals of 5 days in a one month period. Fourier transform
      infrared spectroscopy (FTIR), X-ray diffraction, and differential scanning
      calorimetry confirmed the electrostatic interaction and hydrogen bond formation
      between the carrier and core. The result showed that hollow ACRU/CS nanocapsules
      (ACRU/CS NPs) and curcumin-loaded ACRU/CS nanoparticles (Cur-ACRU/CS NPs) were
      homogenized spherical with average sizes of 200-450 nm and zeta potential of +15
      mV. Encapsulation and loading efficiencies were 72% and 5.4%, respectively. In
      vitro release study using simulated gastro (SGF) and intestinal fluids (SIF)
      showed controlled release of curcumin in 6 h of exposure. Additionally, the Cur
      ACRU/CS NPs are nontoxic to cultured Caco-2 cells, and the permeability assay
      indicated that Cur-ACRU/CS NPs had improved permeability efficiency of free
      curcumin through the Caco-2 cell monolayer. The findings suggest that ACRU/CS NPs
      can be used for encapsulation and delivery of curcumin in functional foods.

PMID- 29451797
TI  - Unimolecular Fragmentation of Deprotonated Diproline [Pro2-H]- Studied by
      Chemical Dynamics Simulations and IRMPD Spectroscopy.
AB  - Dissociation chemistry of the diproline anion [Pro2-H]- is studied using chemical
      dynamics simulations coupled with quantum-chemical calculations and RRKM
      analysis. Pro2- is chosen due to its reduced size and the small number of sites
      where deprotonation can take place. The mechanisms leading to the two dominant
      collision-induced dissociation (CID) product ions are elucidated. Trajectories
      from a variety of isomers of [Pro2-H]- were followed in order to sample a larger
      range of possible reactivity. While different mechanisms yielding y1- product
      ions are proposed, there is only one mechanism yielding the b2- ion. This
      mechanism leads to formation of a b2- fragment with a diketopiperazine structure.
      The sole formation of a diketopiperazine b2 sequence ion is experimentally
      confirmed by infrared ion spectroscopy of the fragment anion. Furthermore,
      collisional and internal energy activation simulations are used in parallel to
      identify the different dynamical aspects of the observed reactivity.

PMID- 29451798
TI  - Unraveling the Nature of Active Sites in Ethanol Electro-oxidation by Site
      Specific Marking of a Pt Catalyst with Isotope-Labeled 13CO.
AB  - This works deals with the identification of preferential site-specific activation
      at a model Pt surface during a multiproduct reaction. The (110)-type steps of a
      Pt(332) surface were selectively marked by attaching isotope-labeled 13CO
      molecules to them, and ethanol oxidation was probed by in situ Foureir transfrom
      infrared spectroscopy in order to precisely determine the specific sites at which
      CO2, acetic acid, and acetaldehyde were preferentially formed. The (110) steps
      were active for splitting the C-C bond, but unexpectedly, we provide evidence
      that the pathway of CO2 formation was preferentially activated at (111) terraces,
      rather than at (110) steps. Acetaldehyde was formed at (111) terraces at
      potentials comparable to those for CO2 formation also at (111) terraces, while
      the acetic acid formation pathway became active only when the (110) steps were
      released by the oxidation of adsorbed 13CO, at potentials higher than for the
      formation of CO2 at (111) terraces of the stepped surface.

PMID- 29451799
TI  - Three-Dimensional Integrated X-ray Diffraction Imaging of a Native Strain in
      Multi-Layered WSe2.
AB  - Emerging two-dimensional (2-D) materials such as transition-metal dichalcogenides
      show great promise as viable alternatives for semiconductor and optoelectronic
      devices that progress beyond silicon. Performance variability, reliability, and
      stochasticity in the measured transport properties represent some of the major
      challenges in such devices. Native strain arising from interfacial effects due to
      the presence of a substrate is believed to be a major contributing factor. A full
      three-dimensional (3-D) mapping of such native nanoscopic strain over micron
      length scales is highly desirable for gaining a fundamental understanding of
      interfacial effects but has largely remained elusive. Here, we employ coherent X
      ray diffraction imaging to directly image and visualize in 3-D the native strain
      along the (002) direction in a typical multilayered (~100-350 layers) 2-D
      dichalcogenide material (WSe2) on silicon substrate. We observe significant
      localized strains of ~0.2% along the out-of-plane direction. Experimentally
      informed continuum models built from X-ray reconstructions trace the origin of
      these strains to localized nonuniform contact with the substrate (accentuated by
      nanometer scale asperities, i.e., surface roughness or contaminants); the
      mechanically exfoliated stresses and strains are localized to the contact region
      with the maximum strain near surface asperities being more or less independent of
      the number of layers. Machine-learned multimillion atomistic models show that the
      strain effects gain in prominence as we approach a few- to single-monolayer
      limit. First-principles calculations show a significant band gap shift of up to
      125 meV per percent of strain. Finally, we measure the performance of multiple
      WSe2 transistors fabricated on the same flake; a significant variability in
      threshold voltage and the "off" current setting is observed among the various
      devices, which is attributed in part to substrate-induced localized strain. Our
      integrated approach has broad implications for the direct imaging and
      quantification of interfacial effects in devices based on layered materials or
      heterostructures.

PMID- 29451800
TI  - Visible-Light Photoredox-Catalyzed Iminyl Radical Formation by N-H Cleavage with
      Hydrogen Release and Its Application in Synthesis of Isoquinolines.
AB  - An unprecedented visible-light photoredox-catalyzed iminyl radical formation by N
      H cleavage with H2 release has been developed. Its application in the synthesis
      of various isoquinolines and related polyaromatics in high atom economy at
      ambient temperature by applying a photosensitizer, Acr+-Mes ClO4-, and a new
      cobalt catalyst, Co(dmgH)2(4-CONMe2Py)Cl is reported. Mechanistic investigations
      indicated that the generated iminyl radical initiates the cascade C-N/C-C bonds
      formation and the catalytic cycle occurs by a simultaneous oxidative as well as
      reductive quenching pathway.

PMID- 29451801
TI  - Patterns of Carbon Nanotubes by Flow-Directed Deposition on Substrates with
      Architectured Topographies.
AB  - We develop and perform continuum mechanics simulations of carbon nanotube (CNT)
      deployment directed by a combination of surface topography and rarefied gas flow.
      We employ the discrete elastic rods method to model the deposition of CNT as a
      slender elastic rod that evolves in time under two external forces, namely, van
      der Waals (vdW) and aerodynamic drag. Our results confirm that this self-assembly
      process is analogous to a previously studied macroscopic system, the "elastic
      sewing machine", where an elastic rod deployed onto a moving substrate forms
      nonlinear patterns. In the case of CNTs, the complex patterns observed on the
      substrate, such as coils and serpentines, result from an intricate interplay
      between van der Waals attraction, rarefied aerodynamics, and elastic bending. We
      systematically sweep through the multidimensional parameter space to quantify the
      pattern morphology as a function of the relevant material, flow, and geometric
      parameters. Our findings are in good agreement with available experimental data.
      Scaling analysis involving the relevant forces helps rationalize our
      observations.

PMID- 29451802
TI  - Nanoscale Mapping and Spectroscopy of Nonradiative Hyperbolic Modes in Hexagonal
      Boron Nitride Nanostructures.
AB  - The inherent crystal anisotropy of hexagonal boron nitride (hBN) provides the
      ability to support hyperbolic phonon polaritons, that is, polaritons that can
      propagate with very large wave vectors within the material volume, thereby
      enabling optical confinement to exceedingly small dimensions. Indeed, previous
      research has shown that nanometer-scale truncated nanocone hBN cavities, with
      deep subdiffractional dimensions, support three-dimensionally confined optical
      modes in the mid-infrared. Because of optical selection rules, only a few of the
      many theoretically predicted modes have been observed experimentally via far
      field reflection and scattering-type scanning near-field optical microscopy (s
      SNOM). The photothermal induced resonance (PTIR) technique probes optical and
      vibrational resonances overcoming weak far-field emission by leveraging an atomic
      force microscope (AFM) probe to transduce local sample expansion caused by light
      absorption. Here we show that PTIR enables the direct observation of previously
      unobserved, dark hyperbolic modes of hBN nanostructures. Leveraging these optical
      modes and their wide range of angular and radial momenta could provide a new
      degree of control over the electromagnetic near-field concentration, polarization
      in nanophotonic applications.

PMID- 29451803
TI  - Fluoroethylene Carbonate Induces Ordered Electrolyte Interface on Silicon and
      Sapphire Surfaces as Revealed by Sum Frequency Generation Vibrational
      Spectroscopy and X-ray Reflectivity.
AB  - The cyclability of silicon anodes in lithium ion batteries (LIBs) is affected by
      the reduction of the electrolyte on the anode surface to produce a coating layer
      termed the solid electrolyte interphase (SEI). One of the key steps for a major
      improvement of LIBs is unraveling the SEI's structure-related diffusion
      properties as charge and discharge rates of LIBs are diffusion-limited. To this
      end, we have combined two surface sensitive techniques, sum frequency generation
      (SFG) vibrational spectroscopy, and X-ray reflectivity (XRR), to explore the
      first monolayer and to probe the first several layers of electrolyte,
      respectively, for solutions consisting of 1 M lithium perchlorate (LiClO4) salt
      dissolved in ethylene carbonate (EC) or fluoroethylene carbonate (FEC) and their
      mixtures (EC/FEC 7:3 and 1:1 wt %) on silicon and sapphire surfaces. Our results
      suggest that the addition of FEC to EC solution causes the first monolayer to
      rearrange itself more perpendicular to the anode surface, while subsequent layers
      are less affected and tend to maintain their, on average, surface-parallel
      arrangements. This fundamental understanding of the near-surface orientation of
      the electrolyte molecules can aid operational strategies for designing high
      performance LIBs.

PMID- 29451804
TI  - Pediatric Acute Respiratory Distress Syndrome: Increase the Positive End
      Expiratory Pressure?

PMID- 29451805
TI  - Loss and formation of malodorous volatile sulfhydryl compounds during wine
      storage.
AB  - Volatile sulfur compounds (VSCs), particularly low molecular weight sulfhydryls
      like hydrogen sulfide (H2S) and methanethiol (MeSH), are often observed in wines
      with sulfurous off-aromas. Recent work has shown both H2S and MeSH can increase
      up to a few uM (> 40 ug/L) during anoxic storage, but the identity of the latent
      sources of these sulfhydryls is still disputed. This review critically evaluates
      the latent precursors and pathways likely to be responsible for the loss and
      formation of these sulfhydryls during wine storage based on the existing enology
      literature as well as studies from food chemistry, geochemistry, biochemistry,
      and synthetic chemistry. We propose that three precursor classes have sufficient
      concentration and metastability to serve as latent sulfhydryl precursors in wine:
      1) transition metal-sulfhydryl complexes, particularly those formed following
      Cu(II) addition, which are released under anoxic conditions through an unknown
      mechanism; 2) asymmetric disulfides, polysulfanes, and (di)organopolysulfanes
      formed through transition-metal mediated oxidation (e.g., Cu(II)) of sulfhydryls
      or pesticide degradation, and released through sulfitolysis, metal-catalyzed
      thiol-disulfide exchange or related reactions; 3) S-alkylthioacetates, primarily
      formed during fermentation, and releasable hydrolytically. Some evidence also
      exists for S-amino acids serving as precursors. Based on these findings, we
      propose a "decision tree" approach to choosing appropriate strategies for
      managing wines with sulfurous off-aromas.

PMID- 29451806
TI  - High-Wattage E-Cigarettes Induce Tissue Hypoxia and Lower Airway Injury: A
      Randomized Clinical Trial.

PMID- 29451807
TI  - Coenzyme Q10: From bench to clinic in aging diseases, a translational review.
AB  - Coenzyme Q10 (CoQ10) is a ubiquitous molecule present in all eukaryotic organisms
      whose principal role in the cell is related to its participation in the electron
      transport chain in the inner mitochondrial membrane. CoQ10 plays a major role in
      the control of cell redox status, and both the amount and functionality of this
      molecule have been related to the regulation of reactive oxygen species
      generation. Numerous reports can be found discussing the implications of CoQ10
      supplementation in human studies and clinical trials related to aging. However,
      few reviews have made an updating through the translational point of view to
      integrate both basic and clinical aspects. The aim of this paper is to review our
      current knowledge from CoQ10 implications at biochemical and physiological level,
      in order to unravel the molecular mechanisms involved in its application in
      clinical practice. Although the importance of CoQ10 has been mainly attributed to
      its role as an agent for energy transduction in mitochondria, new functions for
      CoQ10 have been described in the recent past years, including anti-inflammatory
      effects, gene expression regulation and lipid bilayer membranes stabilization,
      which explain its involvement in aging and age-related diseases such as
      cardiovascular diseases, renal failure and neurodegenerative diseases.

PMID- 29451808
TI  - Implications of recent research on microstructure modifications, through heat
      related processing and trait alteration to bio-functions, molecular thermal
      stability and mobility, metabolic characteristics and nutrition in cool-climate
      cereal grains and other types of seeds with advanced molecular techniques.
AB  - The cutting-edge synchrotron radiation based and globar-sourced vibrational
      infrared microspectroscopy have recently been developed. These novel techniques
      are able to reveal structure features at cellular and molecular levels with the
      tested tissues being intact. However, to date, the advanced techniques are
      unfamiliar or unknown to food and feed scientists and have not been used to study
      the molecular structure changes in cool-climate cereal grain seeds and other
      types of bio-oil and bioenergy seeds. This article aims to provide some recent
      research in cool-climate cereal grains and other types of seeds on molecular
      structures and metabolic characteristics of carbohydrate and protein, and
      implication of microstructure modification through heat-related processing and
      trait alteration to bio-functions, molecular thermal stability and mobility, and
      nutrition with advanced molecular techniques- synchrotron radiation based and
      globar-sourced vibrational infrared microspectroscopy in the areas of (1)
      Inherent microstructure of cereal grain seeds; (2) The nutritional values of
      cereal grains; (3) Impact and modification of heat-related processing to cereal
      grain; (4) Conventional nutrition evaluation methodology; (5) Synchrotron
      radiation-based and globar-sourced vibrational (micro)-spectroscopy for molecular
      structure study and molecular thermal stability and mobility, and (6) Recent
      molecular spectroscopic technique applications in research on raw, traits altered
      and processed cool-climate cereal grains and other types of seeds. The
      information described in this article gives better insights of research progress
      and update in cool-climate cereal grains and other seeds with advanced molecular
      techniques.

PMID- 29451809
TI  - Intensifying Long-Acting beta-Agonist/Corticosteroid Therapy at Acute
      Exacerbations of Chronic Obstructive Pulmonary Disease.

PMID- 29451810
TI  - Recent developments in the food quality detected by non-invasive nuclear magnetic
      resonance technology.
AB  - Nuclear magnetic resonance (NMR) is a rapid, accurate and non-invasive technology
      and widely used to detect the quality of food, particularly to fruits and
      vegetables, meat and aquatic products. This review is a survey of recent
      developments in experimental results for the quality of food on various NMR
      technologies in processing and storage over the past decade. Following a
      discussion of the quality discrimination and classification of food, analysis of
      food compositions and detection of physical, chemical, structural and
      microbiological properties of food are outlined. Owing to high cost, low
      detection limit and sensitivity, the professional knowledge involved and the
      safety issues related to the maintenance of the magnetic field, so far the
      practical applications are limited to detect small range of food. In order to
      promote applications for a broader range of foods further research and
      development efforts are needed to overcome the limitations of NMR in the
      detection process. The needs and opportunities for future research and
      developments are outlined.

PMID- 29451811
TI  - Role of Tendoscopy in Treating Stage II Posterior Tibial Tendon Dysfunction.
AB  - BACKGROUND: Stage II tibialis posterior tendon dysfunction (PTTD) resistant to
      conservative therapies is usually treated with invasive surgery. Posterior tibial
      tendoscopy is a novel technique being used in the assessment and treatment of
      posterior tibial pathology. The aims of this study were (1) to clarify the role
      of posterior tibial tendon tendoscopy in treating stage II PTTD, (2) to
      arthroscopically classify spring ligament lesions, and (3) to compare the
      arthroscopic assessment of spring ligament lesions with magnetic resonance
      imaging (MRI) and ultrasonographic (US) data. METHODS: We reviewed prospectively
      collected data on 16 patients affected by stage II PTTD and treated by
      tendoscopy. We report the reoperation rate and functional outcomes evaluated by
      comparing pre- and postoperative visual analogic scale for pain (VAS-pain) and
      the Short-Form Health Survey (SF-36; with its physical [PCS] and mental [MCS]
      components). Postoperative satisfaction was assessed using a VAS-satisfaction
      scale. One patient was lost to follow-up. Spring ligament lesions were
      arthroscopically classified in 3 stages. Discrepancies between preoperative
      imaging and intraoperative findings were evaluated. RESULTS: At a mean of 25.6
      months' follow-up, VAS-pain ( P < .001), SF-36 PCS ( P = .039), and SF-36 MCS ( P
      < .001) significantly improved. The mean VAS-satisfaction score was 75.3/100.
      Patients were relieved from symptoms in 80% of cases, while 3 patients required
      further surgery. MRI and US were in agreement with intraoperative data in 92% and
      67%, respectively, for the tendon assessment and in 78% and 42%, respectively,
      for the spring ligament. CONCLUSIONS: Tendoscopy may be considered a valid
      therapeutic tool in the treatment of stage II PTTD resistant to conservative
      treatment. It provided objective and subjective encouraging results that could
      allow continued conservative therapy while avoiding more invasive surgery in most
      cases. MRI and US were proven more useful in detecting PT lesions than spring
      ligament tears. Further studies on PT could use this tendoscopic classification
      to standardize its description. LEVEL OF EVIDENCE: Level IV, therapeutic study,
      case series.

PMID- 29451812
TI  - Efficacy of nebulized liposomal amphotericin B in the treatment of ABPA in an
      HIV/HBV co-infected man: Case report and literature review.

PMID- 29451813
TI  - Modulatory Effects of Alkaloid Extract from Gongronema latifolium (Utazi) and
      Lasianthera africana (Editan) on Activities of Enzymes Relevant to
      Neurodegeneration.
AB  - Most alkaloids are produced by plants as a defense mechanism against herbivores.
      Since alkaloids are known to possess pharmacological effects, this study sought
      to investigate the in vitro modulatory effect of alkaloid obtained from two
      commonly consumed vegetables in southern Nigeria, Lasianthera africana (editan)
      and Gongronema latifolium (utazi), on some enzyme activities relevant to
      neurodegeneration. Effects of the alkaloids on cholinesterases
      (acetylcholinesterase [AChE] and butyrylcholinesterase [BChE]) and monoamine
      oxidase (MAO) activities were determined in vitro. In addition, Fe2+ chelating
      ability as well as radical-scavenging abilities were determined. Alkaloid profile
      was also determined using gas chromatography coupled with flame ionization
      detector (GC-FID). The results revealed that the alkaloids inhibited AChE, BChE,
      and MAO activities in a concentration-dependent manner, such that the alkaloid
      from G. latifolium showed higher enzyme inhibition (AChE [IC50 = 87.39 ug/ml],
      BChE [IC50 = 118.65 ug/ml], and MAO [IC50 = 61.37 ug/ml]) than L. africana (AChE
      = 115.60 ug/ml; BChE = 169.48 ug/ml; MAO = 73.72 ug/ml). In addition, GC-FID
      analysis revealed abundance of choline in both extracts. Gongronema latifolium
      and Lasianthera africana alkaloid extracts inhibit enzymes (acetylcholinesterase,
      butyrylcholinesterase, and monoamine oxidase) implicated in neurodegenerative
      diseases. Hence, these vegetables could offer dietary supplement in the
      management of neurodegenerative diseases.

PMID- 29451814
TI  - Variability in asthma quality and costs in children with different Medicaid
      insurance plans in Maricopa County.
AB  - OBJECTIVE: To describe the variation in asthma quality and costs among children
      with different Medicaid insurance plans. METHODS: We used 2013 data from the
      Center for Health Information and Research, which houses a database that includes
      individuals who have Medicaid insurance in Arizona. We analyzed children ages 2
      17 years-old who lived in Maricopa County, Arizona. Asthma medication ratio (AMR,
      a measure of appropriate asthma medication use), outpatient follow-up within 2
      weeks after asthma-related hospitalization (a measure of continuity of care),
      asthma-related hospitalizations, and all emergency department (ED) visits were
      the primary quality metrics. Direct costs were reported in 2013 $US dollars. We
      used one-way analysis of variance to compare the health plans for AMR and per
      member cost (total, ER, and hospital), and the chi-squared test for the
      outpatient follow-up measure. We used coefficient of variation to identify
      variation of each measure across all individuals in the study. RESULTS: In 2013,
      90,652 children in Maricopa County were identified as having asthma. The average
      patient-weighted AMR for children with persistent asthma was 0.35, well short of
      the goal of >=0.70, and only 36% of hospitalized asthma patients had outpatient
      follow-up within 2 weeks of hospitalization. AMR, total costs, and ED costs
      varied significantly (p <.0001) when comparing health plans while hospital costs
      and outpatient follow-up showed no significant variation. CONCLUSIONS: Targeting
      appropriate medication use for asthma may help reduce variation, improve
      outcomes, and increase healthcare value for children with asthma and Medicaid
      insurance in the US.

PMID- 29451815
TI  - Gender differences in substance use treatment and substance use among adults on
      probation.
AB  - BACKGROUND: Although many formal and informal substance use treatment programs
      were originally designed for men, no studies have investigated how gender affects
      the use of substance use treatment modalities, and how gender differences in
      treatment utilization impact substance use in the unique probation context.
      OBJECTIVE: To describe gender differences in use and effectiveness of substance
      use treatment modalities (formal and informal) among probationers. METHODS:
      Longitudinal data were obtained from 335 individuals (93 women) who participated
      in the Motivational Assessment Program to Initiate Treatment (MAPIT) study.
      Timeline follow-back measures were used to quantify daily substance use and
      treatment modality (formal treatment included inpatient and outpatient treatment;
      informal treatment included self-help, religious, and all other group meetings).
      Multivariate generalized estimating equations were used to examine relationships
      between gender, treatment, and substance use. RESULTS: Gender was not associated
      with alcohol use. Use of formal treatment programs reduced the odds of alcohol
      use by 15%. The probability of alcohol use was the lowest (8%) for men who
      participated in formal treatment. For men using informal treatment programs, the
      probability of alcohol use was 11%. The probability of alcohol use for women was
      similar regardless of the type of treatment utilization (15-16%). No differences
      in illicit drug use by gender or type of treatment were detected. CONCLUSION:
      This research found limited evidence of a relationship between gender, substance
      use treatment modality, and alcohol use. These findings have clinical
      significance in that both formal and informal treatment approaches are similarly
      effective across both men and women.

PMID- 29451816
TI  - Effects of teriparatide on morphology of aortic calcification in aged
      hyperlipidemic mice.
AB  - Calcific aortic vasculopathy correlates with bone loss in osteoporosis in an age
      independent manner. Prior work suggests that teriparatide, the bone anabolic
      treatment for postmenopausal osteoporosis, may inhibit the onset of aortic
      calcification. Whether teriparatide affects the progression of preexisting aortic
      calcification, widespread among this patient population, is unknown. Female
      apolipoprotein E-deficient mice were aged for over 1 yr to induce aortic
      calcification, treated for 4.5 wk with daily injections of control vehicle (PBS),
      40 ug/kg teriparatide (PTH40), or 400 ug/kg teriparatide (PTH400), and assayed
      for aortic calcification by microcomputed tomography (microCT) before and after
      treatment. In a followup cohort, aged female apolipoprotein E-deficient mice were
      treated with PBS or PTH400 and assayed for aortic calcification by serial microCT
      and micropositron emission tomography. In both cohorts, aortic calcification
      detected by microCT progressed similarly in all groups. Mean aortic 18F-NaF
      incorporation, detected by serial micropositron emission tomography, increased in
      the PBS-treated group (+14 +/- 5%). In contrast, 18F-NaF incorporation decreased
      in the PTH400-treated group (-33 +/- 20%, P = 0.03). Quantitative histochemical
      analysis by Alizarin red staining revealed a lower mineral surface area index in
      the PTH400-treated group compared with the PBS-treated group ( P = 0.04).
      Furthermore, Masson trichrome staining showed a significant increase in collagen
      deposition in the left ventricular myocardium of mice that received PTH400 [2.1
      +/- 0.6% vs. control mice (0.5 +/- 0.1%), P = 0.02]. In summary, although
      teriparatide may not affect the calcium mineral content of aortic calcification,
      it reduces 18F-NaF uptake in calcified lesions, suggesting the possibility that
      it may reduce mineral surface area with potential impact on plaque stability. NEW
      & NOTEWORTHY Parathyroid hormone regulates bone mineralization and may also
      affect vascular calcification, which is an important issue, given that its active
      fragment, teriparatide, is widely used for the treatment of osteoporosis. To
      determine whether teriparatide alters vascular calcification, we imaged aortic
      calcification in mice treated with teriparatide and control mice. Although
      teriparatide did not affect the calcium content of cardiovascular deposits, it
      reduced their fluoride tracer uptake.

PMID- 29451818
TI  - Overexpression of heart-specific small subunit of myosin light chain phosphatase
      results in heart failure and conduction disturbance.
AB  - Mutations in genes encoding components of the sarcomere cause cardiomyopathy,
      which is often associated with abnormal Ca2+ sensitivity of muscle contraction.
      We have previously shown that a heart-specific myosin light chain phosphatase
      small subunit (hHS-M21) increases the Ca2+ sensitivity of muscle contraction. The
      aim of the present study was to investigate the function of hHS-M21 in vivo and
      the causative role of abnormal Ca2+ sensitivity in cardiomyopathy. We generated
      transgenic mice with cardiac-specific overexpression of hHS-M21. We confirmed
      that hHS-M21 increased the Ca2+ sensitivity of cardiac muscle contraction in
      vivo, which was not followed by an increased phosphorylation of myosin light
      chain 2 isoforms. hHS-M21 transgenic mice developed severe systolic dysfunction
      with myocardial fibrosis and degeneration of cardiomyocytes in association with
      sinus bradycardia and atrioventricular conduction defect. The contractile
      dysfunction and cardiac fibrosis were improved by treatment with the Rho kinase
      inhibitor fasudil. Our findings suggested that the overexpression of hHS-M21
      results in cardiac dysfunction and conduction disturbance via non-myosin light
      chain 2 phosphorylation-dependent regulation. NEW & NOTEWORTHY The present study
      is the first to develop mice with transgenic overexpression of a heart-specific
      myosin light chain phosphatase small subunit (hHS-M21) and to examine the effects
      of hHS-M21 on cardiac function. Elevation of hHS-M21 induced heart failure with
      myocardial fibrosis and degeneration of cardiomyocytes accompanied by
      supraventricular arrhythmias.

PMID- 29451819
TI  - Protection from chronic stress- and depressive symptom-induced vascular
      endothelial dysfunction in female rats is abolished by preexisting metabolic
      disease.
AB  - While it is known that chronic stress and clinical depression are powerful
      predictors of poor cardiovascular outcomes, recent clinical evidence has
      identified correlations between the development of metabolic disease and
      depressive symptoms, creating a combined condition of severely elevated
      cardiovascular disease risk. In this study, we used the obese Zucker rat (OZRs)
      and the unpredictable chronic mild stress (UCMS) model to determine the impact of
      preexisting metabolic disease on the relationship between chronic
      stress/depressive symptoms and vascular function. Additionally, we determined the
      impact of metabolic syndrome on sex-based protection from chronic
      stress/depressive effects on vascular function in female lean Zucker rats (LZRs).
      In general, vasodilator reactivity was attenuated under control conditions in
      OZRs compared with LZRs. Although still impaired, conduit arterial and resistance
      arteriolar dilator reactivity under control conditions in female OZRs was
      superior to that in male or ovariectomized (OVX) female OZRs, largely because of
      better maintenance of vascular nitric oxide and prostacyclin levels. However,
      imposition of metabolic syndrome in combination with UCMS in OZRs further
      impaired dilator reactivity in both vessel subtypes to a similarly severe extent
      and abolished any protective effect in female rats compared with male or OVX
      female rats. The loss of vascular protection in female OZRs with UCMS was
      reflected in vasodilator metabolite levels, which closely matched those in male
      and OVX female OZRs subjected to UCMS. These results suggest that presentation of
      metabolic disease in combination with depressive symptoms can overwhelm the
      vasoprotection identified in female rats and, thereby, may reflect a severe
      impairment to normal endothelial function. NEW & NOTEWORTHY This study addresses
      the protection from chronic stress- and depression-induced vascular dysfunction
      identified in female compared with male or ovariectomized female rats. We
      determined the impact of preexisting metabolic disease, a frequent comorbidity of
      clinical depression in humans, on that vascular protection. With preexisting
      metabolic syndrome, female rats lost all protection from chronic
      stress/depressive symptoms and became phenotypically similar to male and
      ovariectomized female rats, with comparably poor vasoactive dilator metabolite
      profiles.

PMID- 29451820
TI  - The HCM-linked W792R mutation in cardiac myosin-binding protein C reduces C6
      FnIII domain stability.
AB  - Cardiac myosin-binding protein C (cMyBP-C) is a functional sarcomeric protein
      that regulates contractility in response to contractile demand, and many
      mutations in cMyBP-C lead to hypertrophic cardiomyopathy (HCM). To gain insight
      into the effects of disease-causing cMyBP-C missense mutations on contractile
      function, we expressed the pathogenic W792R mutation (substitution of a highly
      conserved tryptophan residue by an arginine residue at position 792) in mouse
      cardiomyocytes lacking endogenous cMyBP-C and studied the functional effects
      using three-dimensional engineered cardiac tissue constructs (mECTs). Based on
      complete conservation of tryptophan at this location in fibronectin type II
      (FnIII) domains, we hypothesized that the W792R mutation affects folding of the
      C6 FnIII domain, destabilizing the mutant protein. Adenoviral transduction of
      wild-type (WT) and W792R cDNA achieved equivalent mRNA transcript abundance, but
      not equivalent protein levels, with W792R compared with WT controls. mECTs
      expressing W792R demonstrated abnormal contractile kinetics compared with WT
      mECTs that were nearly identical to cMyBP-C-deficient mECTs. We studied whether
      common pathways of protein degradation were responsible for the rapid degradation
      of W792R cMyBP-C. Inhibition of both ubiquitin-proteasome and lysosomal
      degradation pathways failed to increase full-length mutant protein abundance to
      WT equivalence, suggesting rapid cytosolic degradation. Bacterial expression of
      WT and W792R protein fragments demonstrated decreased mutant stability with
      altered thermal denaturation and increased susceptibility to trypsin digestion.
      These data suggest that the W792R mutation destabilizes the C6 FnIII domain of
      cMyBP-C, resulting in decreased full-length protein expression. This study
      highlights the vulnerability of FnIII-like domains to mutations that alter domain
      stability and further indicates that missense mutations in cMyBP-C can cause
      disease through a mechanism of haploinsufficiency. NEW & NOTEWORTHY This study is
      one of the first to describe a disease mechanism for a missense mutation in
      cardiac myosin-binding protein C linked to hypertrophic cardiomyopathy. The
      mutation decreases stability of the fibronectin type III domain and results in
      substantially reduced mutant protein expression dissonant to transcript
      abundance.

PMID- 29451823
TI  - Evaluation of Fetal Intestinal Cell Growth and Antimicrobial Biofunctionalities
      of Donor Human Milk After Preparative Processes.
AB  - BACKGROUND: Donor human milk is considered the next best nutrition following
      mother's own milk to prevent neonatal infection and necrotizing enterocolitis in
      preterm infants who are admitted at neonatal intensive care unit. However, donor
      milk biofunctionalities after preparative processes have rarely been documented.
      OBJECTIVE: To evaluate biofunctionalities preserved in donor milk after
      preparative processes by cell-based assays. MATERIALS AND METHODS: Ten pools of
      donor milk were produced from 40 independent specimens. After preparative
      processes, including bacterial elimination methods (holder pasteurization and
      cold-sterilization microfiltration) and storage conditions (-20 degrees C
      freezing storage and lyophilization) with varied duration of storage (0, 3, and
      6, months), donor milk biofunctionalities were examined by fetal intestinal cell
      growth and antimicrobial assays. RESULTS: At baseline, raw donor milk exhibited
      193.1% +/- 12.3% of fetal intestinal cell growth and 42.4% +/- 11.8% of
      antimicrobial activities against Escherichia coli. After bacteria eliminating
      processes, growth promoting activity was better preserved in pasteurized donor
      milk than microfiltrated donor milk (169.5% +/- 14.3% versus 146.0% +/- 11.8%,
      respectively; p < 0.005), whereas antimicrobial activity showed no difference
      between groups (38.3% +/- 14.1% versus 53.7% +/- 17.3%, respectively; p = 0.499).
      The pasteurized donor milk was further examined for the effects of storage
      conditions at 3 and 6 months. Freezing storage, but not lyophilization, could
      preserve higher growth-promoting activity during 6 months of storage (163.0% +/-
      9.4% versus 72.8% +/- 6.2%, respectively; p < 0.005). Nonetheless, antimicrobial
      activity was lost at 6 months, regardless of the storage methods. CONCLUSIONS:
      This study revealed that fetal intestinal cell growth and antimicrobial assays
      could be applied to measure donor milk biofunctionalities and support the
      utilization of donor milk within 3 months after preparative processes.

PMID- 29451817
TI  - Impact of pulse pressure on cerebrovascular events leading to age-related
      cognitive decline.
AB  - Aging is a modern concept: human life expectancy has more than doubled in less
      than 150 yr in Western countries. Longer life span, however, reveals age-related
      diseases, including cerebrovascular diseases. The vascular system is a prime
      target of aging: the "wear and tear" of large elastic arteries exposed to a
      lifelong pulsatile pressure causes arterial stiffening by fragmentation of
      elastin fibers and replacement by stiffer collagen. This arterial stiffening
      increases in return the amplitude of the pulse pressure (PP), its wave
      penetrating deeper into the microcirculation of low-resistance, high-flow organs
      such as the brain. Several studies have associated peripheral arterial stiffness
      responsible for the sustained increase in PP, with brain microvascular diseases
      such as cerebral small vessel disease, cortical gray matter thinning, white
      matter atrophy, and cognitive dysfunction in older individuals and prematurely in
      hypertensive and diabetic patients. The rarefaction of white matter is also
      associated with middle cerebral artery pulsatility that is strongly dependent on
      PP and artery stiffness. PP and brain damage are likely associated, but the
      sequence of mechanistic events has not been established. Elevated PP promotes
      endothelial dysfunction that may slowly develop in parallel with the accumulation
      of proinflammatory senescent cells and oxidative stress, generating
      cerebrovascular damage and remodeling, as well as brain structural changes. Here,
      we review data suggesting that age-related increased peripheral artery stiffness
      may promote the penetration of a high PP to cerebral microvessels, likely causing
      functional, structural, metabolic, and hemodynamic alterations that could
      ultimately promote neuronal dysfunction and cognitive decline.

PMID- 29451824
TI  - Inadvertently Finding Earth Contamination on Mars Should Not Be a Priority for
      Anyone.

PMID- 29451821
TI  - Protection from vascular dysfunction in female rats with chronic stress and
      depressive symptoms.
AB  - The increasing prevalence and severity of clinical depression are strongly
      correlated with vascular disease risk, creating a comorbid condition with poor
      outcomes but demonstrating a sexual disparity whereby female subjects are at
      lower risk than male subjects for subsequent cardiovascular events. To determine
      the potential mechanisms responsible for this protection against
      stress/depression-induced vasculopathy in female subjects, we exposed male,
      intact female, and ovariectomized (OVX) female lean Zucker rats to the
      unpredictable chronic mild stress (UCMS) model for 8 wk and determined depressive
      symptom severity, vascular reactivity in ex vivo aortic rings and middle cerebral
      arteries (MCA), and the profile of major metabolites regulating vascular tone.
      While all groups exhibited severe depressive behaviors from UCMS, severity was
      significantly greater in female rats than male or OVX female rats. In all groups,
      endothelium-dependent dilation was depressed in aortic rings and MCAs, although
      myogenic activation and vascular (MCA) stiffness were not impacted. Higher
      resolution results from pharmacological and biochemical assays suggested that
      vasoactive metabolite profiles were better maintained in female rats with normal
      gonadal sex steroids than male or OVX female rats, despite increased depressive
      symptom severity (i.e., higher nitric oxide and prostacyclin and lower H2O2 and
      thromboxane A2 levels). These results suggest that female rats exhibit more
      severe depressive behaviors with UCMS but are partially protected from the
      vasculopathy that afflicts male rats and female rats lacking normal sex hormone
      profiles. Determining how female sex hormones afford partial vascular protection
      from chronic stress and depression is a necessary step for addressing the burden
      of these conditions on cardiovascular health. NEW & NOTEWORTHY This study used a
      translationally relevant model for chronic stress and elevated depressive
      symptoms to determine how these factors impact conduit and resistance arteriolar
      function in otherwise healthy rats. While chronic stress leads to an impaired
      vascular reactivity associated with elevated oxidant stress, inflammation, and
      reduced metabolite levels, we demonstrated partial protection from vascular
      dysfunction in female rats with normal sex hormone profiles compared with male or
      ovariectomized female rats.

PMID- 29451825
TI  - Introduction to the Special Section on the Social Cognition and Object Relations
      Scale-Global Rating Method: From Research to Practice.
AB  - There continues to be a need in the field of psychology for measures that
      quantify qualitative data in dynamically rich and clinically meaningful ways. The
      Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G;
      Westen, 1995) is a clinician-rated measure with a strong theoretical foundation
      that assesses sophisticated underlying constructs, specifically 8 dimensions of
      object relations (Stein & Slavin-Mulford, 2018 ). The SCORS-G has steadily
      increased in popularity and this special section of the Journal of Personality
      Assessment reflects this growing interest. In this introduction, we provide
      readers with a brief overview of the 5 articles in this special section and note
      ways in which they reflect and build on the existing SCORS-G empirical
      literature. Contextualizing these articles within the broader literature allows
      us to highlight how the measure is employed in clinical and research settings.
      Each of these 5 articles also highlights areas and opportunities for future
      research that would address gaps in the SCORS-G literature and strengthen the
      utility of the measure. We close by noting how each of studies can be seen as a
      model for future lines of research.

PMID- 29451826
TI  - Flexibility and Rigidity in Object Relational Functioning: Assessing Change in
      Suicidal Ideation and Global Psychiatric Functioning Using the SCORS-G.
AB  - The Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G;
      Westen, 1995 ) has been widely used as an assessment measure of object relational
      functioning across a number of stimuli. This study used the SCORS-G to
      investigate associations between global impairments and rigidity in quality of
      object relations with changes in suicidal ideation and psychiatric functioning
      over time. Participant narratives describing actual interpersonal experiences
      were collected using the Relationship Anecdote Paradigm (Luborsky, 1998 ) from a
      sample of individuals diagnosed with complex psychopathology completing
      residential psychiatric treatment. We found that a greater range in affective
      quality and emotional investment in relationship scores at admission into
      treatment were significantly related to a reduction in suicidal ideation as well
      as improvements in global psychiatric functioning at 5-year follow-up. Thus,
      participants who acknowledged having both healthy as well as troubled
      relationships in their daily lives were less suicidal and less likely to
      experience disruptive psychiatric symptoms over time than those who described
      more restricted or uniform relational experiences on entering treatment.
      Implications for calculating range scores and using various narrative techniques
      when applying the SCORS-G method are discussed.

PMID- 29451827
TI  - Sending the Right Message: Wild Game and the West Africa Ebola Outbreak.
AB  - The unprecedented scale of the Ebola epidemic in West Africa in 2014-15 caught
      the world by surprise. Zaire Ebolavirus had not previously been documented in
      Guinea, Sierra Leone, or Liberia. However, since this strain of filovirus was
      first identified in 1976, scientists have been studying the disease and its
      origins. They have identified forest-dwelling animals that carry the virus, and
      some that die from it, but have yet to isolate how it is transmitted from animals
      to humans. During the height of the Ebola outbreak in West Africa, some public
      health messages addressed the link among Ebola, wild animals, and humans. This
      article analyzes 3 of those health messages and identifies information that is
      inconsistent with scientific research. Two additional examples illustrate more
      accurate public health messages. Until there is greater certainty about the
      nature of the transmission chain, future public health campaigns may be improved
      by timing, placement, images, and wording that provide the most accurate
      information to the most appropriate audience.

PMID- 29451828
TI  - The Effect of Omega-3 Fatty Acids, EPA, and/or DHA on Male Infertility: A
      Systematic Review and Meta-analysis.
AB  - The objective was to evaluate the effect of docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA) on sperm parameters including total sperm
      concentration, sperm motility, sperm DHA, and seminal plasma DHA concentration in
      infertile men. The literature search was conducted in PubMed, Google Scholar, and
      Scopus from January 1, 1990 to December 20, 2017. The systematic review and meta
      analysis were based on randomized controlled trials in infertile men with DHA or
      EPA treatments, either alone or in combination with other micronutrients. Three
      studies met the inclusion criteria: 147 patients in the intervention group and
      143 patients in the control group. The analysis showed that omega-3 treatments
      significantly increased the sperm motility (RR 5.82, 95% CI [2.91, 8.72], p <.
      0001, I2 = 76%) and seminal DHA concentration (RR 1.61, 95% CI [0.15, 3.07], p =.
      03, I2 = 98%). Compared with the controls, the interventions did not affect the
      sperm concentration (RR 0.31, 95% CI [-8.13, 8.76], p =. 94, I2 = 95%) or sperm
      DHA (RR 0.50, 95% CI [-4.17, 5.16], p =. 83, I2 = 99%). The observed
      heterogeneity may be due to administration period and dosage of omega-3 fatty
      acids across the studies. Funnel plot shows no evidence of publication bias. This
      meta-analysis indicates that supplementing infertile men with omega-3 fatty acids
      resulted in a significant improvement in sperm motility and concentration of DHA
      in seminal plasma.

PMID- 29451829
TI  - Survivor Notification of Post-Disaster Mental Health Services: An Integrative
      Review.
AB  - This integrative review identifies notification methods for psychiatric mental
      health services for adult survivors of natural disasters for articles published
      from 2011 through 2016. Databases searched included Scopus, Cochrane Library,
      CINAHL Plus, Ovid MEDLINE, and Ovid PsycINFO. The search was limited to English
      language. Initially, 273 titles/abstracts were reviewed, and 18 articles were
      retained for synthesis. Communication occurs through formal means of health care
      provider referrals and online programs (72%); informal supports are friends,
      family and clergy (28%). Mental health providers have significant impact on
      disaster recovery by developing plans for communication.

PMID- 29451830
TI  - Quality of Life and African American Women Who are Family Caregivers: A
      Literature Review with Implications for Psychiatric Mental Health Advanced
      Practice Registered Nurses.
AB  - PURPOSE: To identify factors affecting the quality of life (QOL) of African
      American women (AAW) family caregivers of individuals with kidney failure.
      METHODS: Ferrans' Conceptual Model of QOL provided the framework for this
      literature review. Included studies were (a) peer- reviewed, (b) published within
      the last ten years, (c) written in English, and (d) examined QOL of AAW family
      caregivers. Using CINAHL(c) and PubMed(c), we found 14 studies that described
      factors associated with these caregivers' QOL. SCOPE: Few studies document the
      QOL of AAW who are family caregivers, especially in the context of kidney
      failure. Psychiatric Mental Health Advanced Practice Registered Nurses need to
      learn about the factors influencing the QOL of these caregivers. RESULTS: No
      studies were found within the last ten years that explored the QOL of AAW family
      caregivers of individuals with kidney failure. Findings reflected the QOL of AAW
      family caregivers in the context of other chronic conditions. Various factors
      such as stress, insomnia, and employment were linked to an impaired QOL.
      Implications for practice, research and education for PMH-APRNs are suggested.
      CONCLUSION: PMH-APRNs are uniquely trained to address many factors that affect
      the QOL of these caregivers and may provide holistic care aimed at promoting
      satisfactory QOL for these caregivers.

PMID- 29451831
TI  - High-Dose Perinatal Folic-Acid Supplementation Alters Insulin Sensitivity in
      Sprague-Dawley Rats and Diminishes the Expression of Adiponectin.
AB  - The possible intake of folate in excess of the recommended upper levels is a
      matter of critical importance. This study was conducted to investigate the
      effects of prenatal and postnatal high folic acid supplementation (FAS) on
      glucose tolerance, insulin sensitivity, lipid metabolism, and expression of
      adiponectin in rats. The study included 20 female rats divided into two groups:
      control group and FAS group (receiving high folic acid supplemented diet). Both
      groups of female rats were mated and pregnancy confirmed. At parturition, the
      diet of 5 dams that were fed with control diet during gestation and their litters
      was changed to FAS diet and continued throughout lactation. Similarly, half of
      the dams that were previously fed with FAS diet during gestation and their
      litters were also changed to control diet. The remaining 5 dams in each group
      continued on their respective diets throughout lactation with their litters.
      Other dams remained on their respective diets throughout lactation. Food and
      water intake, body weight, lipid concentrations, insulin, and the expression of
      adiponectin were determined. Glucose tolerance and insulin sensitivity were also
      measured to evaluate glucose homeostasis. FAS significantly increased the
      postweaning food, water intake, triglyceride, and insulin levels but diminished
      insulin sensitivity in adult offspring. The expression of adiponectin in insulin
      sensitive tissues was also significantly decreased and these were consistent with
      insulin resistance of FAS offspring. High-dose FAS may promote insulin resistance
      and dyslipidemia and disrupt glucose metabolism possibly by depressing
      adiponectin expression. Although this is an animal model and the effects of the
      diets cannot be directly transposed to humans, this study provides indications of
      the possible adverse effects of FAS maternal diet on glucose metabolism in the
      offspring.

PMID- 29451832
TI  - Circulating progenitor cells and their interaction with platelets in patients
      with an acute coronary syndrome.
AB  - CD34+ cells expressing KDR (CD34+/KDR+) represent a small proportion of
      circulating progenitor cells that have the capacity to interact with platelets
      and to differentiate into mature endothelial cells, thus contributing to vascular
      homeostasis and regeneration as well as to re-endothelialization. We investigated
      the levels of CD34+ and CD34+/KDR+ progenitor cells as well as their interaction
      with platelets in acute coronary syndrome (ACS) patients before the initiation
      (baseline) of their treatment with a P2Y12 receptor antagonist, and at 5-days
      post-treatment (follow-up). Sixty-seven consecutive ACS patients and thirty
      healthy subjects (controls) participated in the study. On admission, all patients
      received 325 mg aspirin, followed by 100 mg/day and then were loaded either with
      600 mg clopidogrel or 180 mg ticagrelor, followed by 75 mg/day (n = 36) or 90 mg
      * 2/day (n = 31), respectively. The levels of circulating CD34+ and CD34+/KDR+
      progenitor cells, as well as their interaction with platelets, were determined by
      flow cytometry, before and after activation with ADP, in vitro. The circulating
      levels of CD34+ and CD34+/KDR+ cells in both patient groups at baseline were
      lower compared with controls while they were significantly increased at 5-days of
      follow-up in both groups, this increase being more pronounced in the ticagrelor
      group. The platelet/CD34+ (CD61+/CD34+) conjugates were higher at baseline and
      reduced at follow-up while the platelet/KDR+ (CD61+/KDR+) conjugates were lower
      at baseline and increased at follow-up, both changes being more pronounced in the
      ticagrelor group. ADP activation of control samples significantly increased the
      KDR expression by CD34+ cells and the CD61+/KDR+ conjugates, these parameters
      being unaffected in patients at baseline but increased at follow-up. Short-term
      dual antiplatelet therapy in ACS patients restores the low platelet/KDR+
      conjugates and CD34+ cell levels and improves the low membrane expression levels
      of KDR in these cells, an effect being more pronounced in ticagrelor-treated
      patients. This may represent a pleiotropic effect of antiplatelet therapy towards
      vascular endothelial regeneration.

PMID- 29451833
TI  - Development and pilot testing of a text message vaccine reminder system for use
      during an influenza pandemic.
AB  - In an influenza pandemic, two vaccine doses administered 21 days apart may be
      needed for individuals of all ages to achieve seroprotection. Achieving dose
      series completion can be challenging even for routinely recommended vaccines. To
      prepare for a two-dose influenza pandemic vaccine campaign and promote dose
      series completion and correct dosing intervals, CDC and its partners developed a
      text message-based vaccine reminder system to remind persons who receive a first
      dose of pandemic influenza vaccine to receive the second dose. Taking advantage
      of the high prevalence of cell phones in the United States, the system sent
      second-dose text message reminders and hyperlinks to educational information. The
      system was pilot tested from November 2015 to April 2016 among graduate public
      health students enrolled at four United States universities. Universities were
      selected based on convenience, and each university used a different recruitment
      method. Among 59 volunteers who pilot tested the system and completed a survey,
      57 (92%) felt the system would be helpful during a pandemic. Forty (68%)
      respondents felt the information included in the messages was informative.
      Volunteers recommended including actionable ways to stay healthy during a
      pandemic, though specific suggestions varied. With further development, text
      reminder systems could be used to promote adherence to a two-dose regimen in a
      future pandemic, although audience-specific messaging and other complementary
      systems will likely be needed. Public and private partners can adapt and
      implement this tool in conjunction with their routine patient information systems
      to improve dose-series completion and ensure optimal protection during an
      influenza pandemic.

PMID- 29451834
TI  - Influenza vaccination 2014-2015: Results of a survey conducted among general
      practitioners in Italy.
AB  - INTRODUCTION: The aim of the present study was to evaluate orientation,
      organizational procedures implemented and difficulties faced by general
      practitioners (GPs) during the 2014/15 seasonal influenza vaccination programme,
      as well as GPs' general attitude towards vaccinations. METHODS: An ad hoc online
      survey was developed and administered to general practitioners members of the
      Italian Federation of GPs (Federazione Italiana Medici di Medicina Generale -
      FIMMG). Overall, 10,000 survey invitations were sent. Data were analysed with R
      3.3.2 software for analyses. Odds ratios (OR) were calculated in univariable and
      multivariable analyses. RESULTS: A sample of 1,245 GPs participated in the
      survey. Only slightly more than one third achieved a vaccination coverage
      comprised between 61% and 75%. In over half of the cases, the local health unit
      does not allow the GPs to choose the type of vaccine; 8.8% did not receive
      operational information at the beginning of the vaccination campaign and almost
      half did not receive feedback information at the end of the campaign. Almost
      three quarters reported that the vaccination uptake should increase. One tenth of
      GPs totally disagreed with the statement that vaccinating healthcare workers is
      crucial to prevent and control infections, and one fifth had not been vaccinated
      in the prior decade. DISCUSSION: The efforts made to vaccinate elderly
      individuals did not reach the expected results; still many GPs complained about
      lack of information by the relevant public health institutions and organizational
      difficulties. A stronger commitment of public health authorities would entail a
      higher vaccination uptake.

PMID- 29451835
TI  - Characteristics and Outcomes of Advanced Cancer Patients Who Received Palliative
      Care at a Public Hospital Compared with Those at a Comprehensive Cancer Center.
AB  - BACKGROUND: Patients with advanced cancer experience severe physical,
      psychosocial, and spiritual distress requiring palliative care (PC). There are
      limited literature regarding characteristics and outcomes of patients evaluated
      by PC services at public hospitals (PHs). Objective, Design, Setting/Subjects,
      and Measurements: To compare the outcomes of advanced cancer patients undergoing
      PC at a PH and those at a comprehensive cancer center (CCC). We reviewed 359
      consecutive advanced cancer patients (PH, 180; CCC, 179) undergoing PC. Symptoms
      and outcomes at consultation and first follow-up visit were assessed. Summary
      statistics were used to describe patient characteristics and outcomes. RESULTS:
      The PH and CCC patients differed significantly according to race: 23% white, 39%
      black, and 36% Hispanic patients at the PH versus 66% white, 17% black, and 11%
      Hispanic patients at the CCC (p < 0.0001). Ninety-six (53%) patients at PH and
      178 (99%) at the CCC had health insurance (p < 0.0001). Symptoms at consultation
      at PH and CCC were pain (85% and 91%, respectively; p = 0.0639), fatigue (81% and
      94%, respectively; p = 0.0003), depression (51% and 69%, respectively; p =
      0.0013), anxiety (47% and 75%, respectively; p < 0.0001), and well-being (63% and
      93%, respectively; p < 0.0001). Multiple interventions provided: opioids, reviews
      for polypharmacy, constipation management, and interdisciplinary counseling.
      Median time from outpatient consultation to follow-up was 29 days(range, 1-119
      days) at the PH and 21 days (range, 1-275 days) at the CCC (p = 0.0006). Median
      overall survival time from outpatient consultation was 473 days (95% confidence
      interval [CI], 205-699 days) at PH and 245 days (95% CI, 152-491 days) at CCC (p
      = 0.3408). CONCLUSIONS: Advanced cancer patients at both institutions frequently
      had multiple distressing physical and emotional symptoms, although the frequency
      was higher at CCC. The median overall survival duration was higher at the PH.
      More research is needed.

PMID- 29451836
TI  - Bioavailability Study of Niosomal Salbutamol Sulfate in Metered Dose Inhaler:
      Controlled Pulmonary Drug Delivery.

PMID- 29451837
TI  - Nutritional Supplementation: A Case for L-Carnitine.

PMID- 29451840
TI  - Eugenics: A Very Short Introduction.

PMID- 29451838
TI  - Serotype distribution of Streptococcus pneumoniae and potential impact of
      pneumococcal conjugate vaccines in China: A systematic review and meta-analysis.
AB  - OBJECTIVE: Thirteen-valent pneumococcal conjugate vaccines (PCV13) was licensed
      for optional use in mainland China since 2017, but the uptake is low. To update
      the research evidence for the pneumococcal serotype distribution of pre-PCV era
      and to estimate the potential impact of PCVs, we performed a meta-analysis on the
      relevant publications concerning the Chinese population. METHODS: This systematic
      review and meta-analysis were conducted on the pneumococcal serotype distribution
      publications in mainland China from 2000 to 2016. The literature was searched in
      PubMed, Ovid-EMBASE, Web of Science, CNKI and Wanfang. Heterogeneity and
      publication bias were tested by I2, meta-regression, Egger's and Begg's test. The
      pneumococcal serotype and vaccine serotype coverage rates were pooled using the
      random-effects model in Stata SE 12.0. RESULTS: In total, 85 publications were
      included. Of all 16,945 included pneumococcal isolates, the most common
      serotypes/serogroups were 19F, 19A, 23F, 14, and 6B, that from children were the
      same as above, that from adults>=18 years were 19, 3, 6, 23, and 14. Among
      isolates from children <18 years, the pooled coverage for PCV10 serotypes was
      52.3%, that for PCV13 was 68.4% and that for PPSV23 was 65.5%. Regarding
      individuals >=18 years, the pooled coverage for PCV10 serotypes was 29.7%, that
      for PCV13 was 49.5% and that for PPSV23 was 50.7%. Serotype prevalence and
      vaccine serotype coverage varied by age group, source, and region. CONCLUSIONS:
      The most common pneumococcal serotype in mainland China was 19F. The serotype
      coverage rates of PCV13 and PPSV23 were 50%-68% in mainland China.

PMID- 29451839
TI  - Correlates of Postpartum Visits Among Medicaid Recipients: An Analysis Using
      Claims Data from a Managed Care Organization.
AB  - BACKGROUND: The postpartum care visit (PPCV) plays an important role in ensuring
      the well-being of mother and infant. This study sought to assess correlates of
      PPCV attendance among women who are at high risk of nonattendance. MATERIALS AND
      METHODS: This study used deidentified medical claims data from Virginia Premier-a
      nonprofit Managed Care Organization that provides health insurance for Medicaid
      beneficiaries. The association between various correlates and PPCV attendance was
      examined using multiple logistic regression analyses. RESULTS: Of the 25,692
      women in the study, more than half (50.5%) did not attend a postpartum visit.
      Racial/ethnic minorities and women receiving the majority of their care at
      hospitals, Health Departments, or Federally Qualified Health Centers were more
      likely to attend their postpartum visit. Women who smoked and those who did not
      attend prenatal care had reduced odds of postpartum visit attendance. Age,
      education, and delivery method were not found to be significantly associated with
      PPCV attendance. CONCLUSIONS: Our results highlight factors associated with
      attendance of PPCVs in low income populations. The continued disparity in
      postpartum care utilization compels additional efforts to improve access to
      health services across socioeconomic and demographic boundaries.

PMID- 29451842
TI  - Protective Effect of Leaf Ethanolic Extract Etlingera hemisphaerica Blume Against
      Mercuric Chloride Toxicity in Blood of Mice.
AB  - This research was intended to investigate the protective effect of leaf ethanolic
      extract Etlingera hemisphaerica Blume (LE3H) against mercuric chloride (HgCl2)
      toxicity in blood of mice (Mus musculus). The experimental animals, 95 male M.
      musculus, received drink and food ad libitum. Three materials were tested: LE3H
      (0.13, 0.26, 0.39 mg/g body weight [bw]) was administered by gavage; HgCl2 (5
      mg/kg bw) was administrated by gavage or intraperitoneal injection; and Imunos
      (the nutritional supplement to stimulate the immune system; 0.2 mg/g bw), as a
      positive control for LE3H treatment, was given by gavage. Blood samples were
      taken from the tails for determining number of blood cells. The animals were
      killed by cervical dislocation (CD), and then blood samples were collected from
      the hearts for protein electrophoresis. Results revealed the same number of
      leukocytes with LE3H (0.39 mg/g bw) treatment as with the Imunos treatment. HgCl2
      administration increased leukocytes and decreased erythrocytes; HgCl2
      administration followed by LE3H (0.39 mg/g bw) treatment protected the amount of
      blood cells as well as the control. HgCl2 administration showed a new 125 kDa
      protein and caused overexpression of 48 kDa protein; this protein profile could
      be protected by LE3H (0.39 mg/g bw) treatment as in the control condition. We
      conclude that LE3H provides a protective effect against HgCl2 toxicity in blood
      of M. musculus.

PMID- 29451843
TI  - Caregiver Reactions to Dementia Symptoms: Effects on Coping Repertoire and Mental
      Health.
AB  - Currently, 15 million informal caregivers, most of whom are women, provide care
      for older adults with dementia (Alzheimer's Disease Association, 2016).
      Caregiving for these individuals often creates distress and may adversely affect
      female caregivers' psychosocial and spiritual well-being. Approximately 35% of
      dementia caregivers complain of health deterioration after initiating caregiving
      responsibilities as compared to 19% of caregivers of older adults who do not have
      dementia (Alzheimer's Disease Association, 2016). Persons with dementia exhibit
      symptoms and behaviors that often are challenging for their caregivers. The way
      that caregivers react to these symptoms and behaviors may affect their coping
      repertoire and their mental health. Adequate evaluation of caregiver reactions to
      symptoms of dementia will provide information useful for developing targeted
      interventions to promote optimal health of female dementia caregivers and to
      potentially postpone the need for nursing home or long-term placement of the care
      recipient.

PMID- 29451844
TI  - Pulmonary Delivery of Therapeutic and Diagnostic Gases.
AB  - The 21st Congress for the International Society for Aerosols in Medicine
      included, for the first time, a session on Pulmonary Delivery of Therapeutic and
      Diagnostic Gases. The rationale for such a session within ISAM is that the
      pulmonary delivery of gaseous drugs in many cases targets the same therapeutic
      areas as aerosol drug delivery, and is in many scientific and technical aspects
      similar to aerosol drug delivery. This article serves as a report on the recent
      ISAM congress session providing a synopsis of each of the presentations. The
      topics covered are the conception, testing, and development of the use of nitric
      oxide to treat pulmonary hypertension; the use of realistic adult nasal replicas
      to evaluate the performance of pulsed oxygen delivery devices; an overview of
      several diagnostic gas modalities; and the use of inhaled oxygen as a proton
      magnetic resonance imaging (MRI) contrast agent for imaging temporal changes in
      the distribution of specific ventilation during recovery from
      bronchoconstriction. Themes common to these diverse applications of inhaled gases
      in medicine are discussed, along with future perspectives on development of
      therapeutic and diagnostic gases.

PMID- 29451845
TI  - Relapse of Juvenile Idiopathic Arthritis-Associated Uveitis after Discontinuation
      of Immunomodulatory Therapy.
AB  - PURPOSE: To assess treatment outcomes in juvenile idiopathic arthritis (JIA)
      associated uveitis and relapse rates upon discontinuation of immunomodulatory
      therapy (IMT). METHODS: Medical records of patients with JIA-associated uveitis
      seen at the University of Illinois at Chicago and the F.I. Proctor Foundation
      uveitis clinics from September 14, 1988 to January 5, 2011 were reviewed. The
      main outcome was time to relapse after attempting to discontinue IMT. RESULTS: Of
      66 patients with JIA-associated uveitis, 51 (77%) received IMT as either sole or
      combination therapy. Of a total of 51, 41 (80%) patients achieved corticosteroid
      sparing control. Attempts were made to discontinue treatment in 19/51 (37%)
      patients. Of a total of 19 patients, 13 (68%) attempting to discontinue IMT
      relapsed, with a median time to relapse of 288 days from the time of attempted
      taper/discontinuation (IQR: 108-338). CONCLUSIONS: Corticosteroid-sparing control
      of inflammation was achieved in the majority of patients; however, attempts to
      stop IMT were often unsuccessful. Close follow-up of patients after
      discontinuation of therapy is warranted.

PMID- 29451846
TI  - Link Between the Adult and the Metacercaria of Clinostomum heluans Braun, 1899
      (Trematoda: Clinostomidae) Through DNA Sequences, and its Phylogenetic Position
      Within the Genus Clinostomum Leidy, 1856.
AB  - The phylogenetic position of Clinostomum heluans Braun, 1899 within the genus
      Clinostomum Leidy, 1856 is reported in this study based on sequences of the
      barcoding region of the mitochondrial cytochrome c oxidase subunit 1 gene (
      COX1). Additionally, molecular data are used to link the adult and the
      metacercariae of the species. The metacercariae of C. heluans were found encysted
      infecting the cichlid fish Australoheros sp. in Minas Gerais, Brazil, whereas the
      adults were obtained from the mouth cavity of the Great White Egret, Ardea alba,
      in Campeche, Mexico. The COX1 sequences obtained for the Mexican clinostomes and
      the Brazilian metacercaria were almost identical (0.2% molecular divergence),
      indicating conspecificity. Similar molecular divergence (0.2-0.4%) was found
      between sequences of C. heluans reported here and Clinostomum sp. 6 previously
      obtained from a metacercaria recovered from the cichlid Cichlasoma boliviense in
      Santa Cruz, Bolivia. Both maximum likelihood and Bayesian inference analyses
      unequivocally showed the conspecificity between C. heluans and Clinostomum sp. 6,
      which form a monophyletic clade with high nodal support and very low genetic
      divergence. Moreover, tree topology reveals that C. heluans occupies a basal
      position with respect to New World species of Clinostomum, although a denser
      taxon sampling of species within the genus is further required. The metacercaria
      of C. heluans seems to be specific to cichlid fish because both samples from
      South America were recovered from species of this fish family, although not
      closely related.

PMID- 29451847
TI  - Appropriate Use of Prophylactic Antibiotic Agents in Gynecologic Surgeries at a
      Midwestern Teaching Hospital.
AB  - BACKGROUND: The purpose of this study was to establish compliance with guidelines
      published by the American College of Obstetricians and Gynecologists (ACOG)
      regarding prophylactic antibiotic use in gynecologic surgery at our institution,
      and define areas of improvement to promote antibiotic stewardship. PATIENTS AND
      METHODS: This was a retrospective cohort study at a single, large tertiary care
      and teaching hospital in Kansas. Patients who underwent inpatient or outpatient
      gynecologic surgery during 2013 were included. Based on published guidelines for
      prophylactic antibiotic agents for gynecologic surgery by ACOG, procedures were
      classified as antibiotic-indicated or antibiotic-not-indicated. Chi-square and
      Fisher exact test analysis were used to identify factors associated with
      antibiotic use. RESULTS: Of the 1,735 cases eligible for inclusion, 1,045 (60.2%)
      had antibiotic agents recommended per guidelines, and appropriate antibiotic
      agents were given in 1,031 (98.7%) of those cases. In 690 (39.8%) cases,
      prophylactic antibiotics were either not recommended or the guidelines are not
      well defined. Of the 690 cases without indication for antibiotic agents, 394
      (57.1%) received prophylactic antibiotic agents. Agreement with guidelines varied
      substantially based on patient age, race, insurance status, area of residence,
      and if the procedure was a resident case (p < 0.05). Myomectomy, laparoscopy, and
      ectopic pregnancy procedures received antibiotic agents against recommendations
      96.3%, 75.6%, and 45.5% of the time, respectively. CONCLUSIONS: Peri-operative
      antibiotics are often administered inappropriately to women undergoing
      gynecologic surgeries for which published guidelines are not well defined. Future
      studies need to identify strategies to reduce antibiotic use in surgical
      procedures unlikely to benefit from prophylaxis.

PMID- 29451848
TI  - MR Imaging of Atraumatic Muscle Disorders.
AB  - Atraumatic disorders of skeletal muscles include congenital variants; inherited
      myopathies; acquired inflammatory, infectious, or ischemic disorders; neoplastic
      diseases; and conditions leading to muscle atrophy. These have overlapping
      appearances at magnetic resonance (MR) imaging and are challenging for the
      radiologist to differentiate. The authors organize muscle disorders into four MR
      imaging patterns: (a) abnormal anatomy with normal signal intensity, (b)
      edema/inflammation, (c) mass, and (d) atrophy, highlighting each of their key
      clinical and imaging findings. Anatomic muscle variants, while common, do not
      produce signal intensity alterations and therefore are easily overlooked. Muscle
      edema is the most common pattern but is nonspecific, with a broad differential
      diagnosis. Autoimmune, paraneoplastic, and drug-induced myositis tend to be
      symmetric, whereas infection, radiation-induced injury, and myonecrosis are focal
      asymmetric processes. Architectural distortion in the setting of muscle edema
      suggests one of these latter processes. Intramuscular masses include primary
      neoplasms, metastases, and several benign masslike lesions that simulate
      malignancy. Some lesions, such as lipomas, low-flow vascular malformations,
      fibromatoses, and subacute hematomas, are distinctive, but many intramuscular
      masses ultimately require a biopsy for definitive diagnosis. Atrophy is the
      irreversible end result of any muscle disease of sufficient severity and is the
      dominant finding in disorders such as the muscular dystrophies, denervation
      myopathy, and sarcopenia. This imaging-based classification, in correlation with
      clinical and laboratory data, will aid the radiologist in interpreting MR imaging
      findings in patients with atraumatic muscle disorders. (c)RSNA, 2018.

PMID- 29451849
TI  - A Comprehensive Review of Eggs, Choline, and Lutein on Cognition Across the Life
      span.
AB  - In 2030, one in five Americans will be older than 65 years, and with that an
      increase in the number of individuals who experience loss in cognitive capacity
      is to be expected. At the same time, nutrition within the first 1000 days
      postconception has been suggested to strongly influence cognitive outcomes across
      the life-span in humans. Eggs are a primary source of both choline and the
      xanthophyll carotenoid lutein in the western diet, and both have been suggested
      to influence cognitive function in humans. This comprehensive review critically
      examines the effects of eggs, choline, and lutein on cognition across the life
      span. There seems to be clear scientific evidence to suggest that both choline
      and lutein play a vital role in brain and neurological development during the
      first 1000 days postconception. The extent to which higher intakes of choline
      have the potential to enhance or influence cognition during childhood, adulthood,
      and/or age-related cognitive decline needs further investigation. Emerging but
      consistent research suggests that lutein has the potential to influence cognition
      across the life-span and that sufficient intakes during mid to late adulthood may
      help to ward off age-related cognitive decline. Macular pigment optical density
      (MPOD) seems to be a reliable and consistent biomarker of brain lutein
      concentrations across the life-span and potentially one for clinically assessing
      cognitive status. This review summarizes the current peer-reviewed literature and
      existing gaps in research.

PMID- 29451850
TI  - Determination of 14 aminoglycosides by LC-MS/MS using molecularly imprinted
      polymer solid phase extraction for clean-up.
AB  - An LC-MS/MS method for screening 14 aminoglycosides in foodstuffs of animal
      origin is presented. Its scope includes raw materials and processed ingredients
      but also finished products composed of milk, meat, fish, egg or fat.
      Aminoglycosides are extracted in an acidic aqueous solution, which is first
      recovered after centrifugation, then diluted with a basic buffer and finally
      purified by molecularly imprinted polymer-solid phase extraction (MIP-SPE).
      Analytes are detected within 8 min by ion-pair reversed phase LC-MS/MS. Due to
      the large range of foodstuffs involved, the variability of matrix effects led to
      significant MS signal variations. This was circumvented by systematically
      extracting each sample twice, i.e. 'unspiked' and 'spiked' at the screening
      target concentration of 50 ug kg-1. The method was validated according to the
      European Community Reference Laboratories Residues Guidelines giving false
      negative and false-positive rates <=3% for all compounds. Ruggedness of the
      method was further demonstrated in quality control operations by a second
      laboratory. The 14 aminoglycosides in water-based standard solutions were stable
      for up to 6 months when stored at either -80 degrees C, -20 degrees C or at 4
      degrees C storage temperatures.

PMID- 29451851
TI  - Validation of a pre-existing safety climate scale for the Turkish furniture
      manufacturing industry.
AB  - Understanding the safety climate level is essential to implement a proactive
      safety program. The objective of this study is to explore the possibility of
      having a safety climate scale for the Turkish furniture manufacturing industry
      since there has not been any scale available. The questionnaire recruited 783
      subjects. Confirmatory factor analysis (CFA) tested a pre-existing safety scale's
      fit to the industry. The CFA indicated that the structures of the model present a
      non-satisfactory fit with the data (chi2 = 2033.4, df = 314, p <= 0.001; root
      mean square error of approximation = 0.08, normed fit index = 0.65, Tucker-Lewis
      index = 0.65, comparative fit index = 0.69, parsimony goodness-of-fit index =
      0.68). The results suggest that a new scale should be developed and validated to
      measure the safety climate level in the Turkish furniture manufacturing industry.
      Due to the hierarchical structure of organizations, future studies should
      consider a multilevel approach in their exploratory factor analyses while
      developing a new scale.

PMID- 29451853
TI  - Graphene oxide-coated stir bar sorptive extraction of trace aflatoxins from soy
      milk followed by high performance liquid chromatography-laser-induced
      fluorescence detection.
AB  - Mycotoxins are potential food pollutants produced by fungi. Among them,
      aflatoxins (AFs) are the most toxic. Therefore, AFs were selected as models, and
      a sensitive, simple and green graphene oxide (GO)-based stir bar sorptive
      extraction (SBSE) method was developed for extraction and determination of AFs
      with high performance liquid chromatography-laser-induced fluorescence detector
      (HPLC-LIF). This method improved the sensitivity of AFs detection and solved the
      deposition difficulty of the direct use of GO as adsorbent. Several parameters
      including a spiked amount of NaCl, stirring rate, extraction time and desorption
      time were investigated. Under optimal conditions, the quantitative method had low
      limits of detection of 2.4-8.0 pg/mL, which were better than some reported AFs
      analytical methods. The developed method has been applied to soy milk samples
      with good recoveries ranging from 80.5 to 102.3%. The prepared GO-based SBSE can
      be used as a sensitive screening technique for detecting AFs in soy milk.

PMID- 29451854
TI  - Tracing Stem Cell Division in Adult Neurogenesis.
AB  - Neural stem cells in the ventricular-subventricular zone of the adult brain
      continuously generate differentiated neurons without depleting the stem cell
      pool. In this issue of Cell Stem Cell, Obernier et al. (2018) present the
      surprising finding that this occurs through mostly symmetric divisions that
      either generate two differentiating or two self-renewing daughter cells.

PMID- 29451852
TI  - Delta Opioids: Neuroprotective Roles in Preclinical Studies.
AB  - Since ancient times, opioids have been used clinically and abused recreationally.
      In the early stages (about 1,000 AD) of opium history, an Arab physician,
      Avicenna, administered opioids to control diarrhea and eye diseases. 1 Opioids
      have very strong pain relieving properties and they also regulate numerous
      cellular responses. Opioid receptors are expressed throughout the body, including
      the nervous system, heart, lungs, liver, gastrointestinal tract, and retina. 2-6
      Delta opioid receptors (DORs) are a very attractive target from the perspective
      of both receptor function and their therapeutic potential. Due to a rapid
      progress in mouse mutagenesis and development of small molecules as DOR agonist,
      novel functions and roles of DORs have emerged in recent years. This review
      article focuses on the recent advances in the neuroprotective roles of DOR
      agonists in general and retina neuroprotection in particular. Rather than being
      exhaustive, this review highlights the selected studies of DOR function in
      neuroprotection. We also highlight our preclinical studies using rodent models to
      demonstrate the potentials of DOR agonists for retinal neuroprotection. Based on
      existing literature and our recently published data on the eye, DOR agonists
      possess therapeutic abilities that protect the retina and optic nerve injury
      against glaucoma and perhaps other retinopathies as well. This review also
      highlights the signaling events associated with DOR for neuroprotection in the
      eye. There is a need for translational research on DORs to recognize their
      potential for clinical application such as in glaucoma.

PMID- 29451855
TI  - In Vivo Labeling by CD73 Marks Multipotent Stromal Cells and Highlights
      Endothelial Heterogeneity in the Bone Marrow Niche.
AB  - Despite much work studying ex vivo multipotent stromal cells (MSCs), the identity
      and characteristics of MSCs in vivo are not well defined. Here, we generated a
      CD73-EGFP reporter mouse to address these questions and found EGFP+ MSCs in
      various organs. In vivo, EGFP+ mesenchymal cells were observed in fetal and adult
      bones at proliferative ossification sites, while in solid organs EGFP+ cells
      exhibited a perivascular distribution pattern. EGFP+ cells from the bone
      compartment could be clonally expanded ex vivo from single cells and displayed
      trilineage differentiation potential. Moreover, in the central bone marrow CD73
      EGFP+ specifically labeled sinusoidal endothelial cells, thought to be a critical
      component of the hematopoietic stem cell niche. Purification and molecular
      characterization of this CD73-EGFP+ population revealed an endothelial subtype
      that also displays a mesenchymal signature, highlighting endothelial cell
      heterogeneity in the marrow. Thus, the CD73-EGFP mouse is a powerful tool for
      studying MSCs and sinusoidal endothelium.

PMID- 29451856
TI  - A D1424N mutation in the MYH9 gene results in macrothrombocytopenia and
      granulocytic inclusion bodies in a Chinese inherited macrothrombocytopenia
      pedigree.

PMID- 29451857
TI  - MicroRNAs as predictive biomarkers of response to tyrosine kinase inhibitor
      therapy in metastatic renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) accounts for 2%-3% of all malignant tumours. The first
      choice treatment in metastatic RCC (mRCC) patients is tyrosine kinase inhibitors
      (TKIs). Although TKIs may prolong survival of the treated patients who are not
      primary resistant, almost all of them will eventually develop secondary
      resistance to the treatment after a progression-free period. To predict treatment
      response, thus, we need efficient biomarkers for rational indication of TKIs in
      mRCC. MicroRNAs (miRNAs) not only play important roles in the pathogenesis of
      many cancers, including RCC but also have been shown to serve as promising
      diagnostic, prognostic and predictive biomarkers in various cancers. However, the
      potential of miRNAs to predict response to therapy with TKIs in mRCC has not yet
      gained sufficient attention. Because personalisation of the TKIs indication in
      mRCC presents an important unmet medical need, we summarise research on this
      topic and give an overall insight on the current knowledge in this field.

PMID- 29451858
TI  - Cerebrospinal fluid microRNAs as diagnostic biomarkers in brain tumors.
AB  - Cerebrospinal fluid (CSF) is a body fluid that has many important functions and
      is in direct contact with the extracellular environment of the central nervous
      system (CNS). CSF serves as both the communication channel allowing the
      distribution of various substances among the CNS cells and the storage facility
      for the waste products these cells release. For these reasons, CSF is a potential
      source of diagnostic biomarkers of many CNS diseases, including brain tumors.
      Recent studies have revealed that CSF also contains circulating microRNAs
      (miRNAs), short non-coding RNAs that have been described as biomarkers in many
      cancers. However, CSF miRNAs are difficult to detect, which is why researchers
      face major challenges, including technological difficulties in its detection and
      its lack of standardization. Therefore, this review aims (i) to highlight the
      potential of CSF miRNAs as diagnostic, prognostic and predictive biomarkers in
      brain tumors, and (ii) to summarize technological approaches for detection of CSF
      miRNAs.

PMID- 29451859
TI  - Harmonization of PCR-based detection of intestinal pathogens: experiences from
      the Dutch external quality assessment scheme on molecular diagnosis of protozoa
      in stool samples.

PMID- 29451860
TI  - A hierarchical Bayesian tri-variate analysis on factors associated with
      anthropometric measures in a large sample of children and adolescents: the
      CASPIAN-IV study.
AB  - BACKGROUND: This study aimed to assess determinants of anthropometric measures in
      a nationally representative sample of Iranian children and adolescents. METHODS:
      This nationwide study was conducted among 13,280 students, aged 6-18 years, who
      were randomly selected from 30 provinces in Iran. Anthropometric measures were
      determined by calibrated instruments. Demographic and socio-economic (SES)
      variables, lifestyle behaviors, family history of chronic disease and prenatal
      factors were studied, as well. A hierarchical Bayesian tri-variate analysis was
      used to assess the factors associated with obesity measures of the body mass
      index (BMI), waist-to-height ratio (WHtR) and wrist circumference (WrC). RESULTS:
      The results showed that the BMI was associated with SES score, family history of
      obesity, family history of diabetes mellitus, physical inactivity, screen time,
      duration of sleep, breakfast consumption, birth weight, breastfeeding, junk food
      and place of residence (urban-rural). All these factors were also significantly
      associated with WrC except for consumption of junk food. Many of these factors
      had a partial but significant relationship with WHtR. CONCLUSIONS: Various
      factors contribute to obesity. Preventive and educational programs on manageable
      factors such as increasing physical activity, eating breakfast and limiting TV or
      screen time could be helpful in controlling obesity in schoolchildren and
      reducing associated complications.

PMID- 29451861
TI  - Induction of labor in twin gestation: can we predict success?

PMID- 29451862
TI  - Neonatal resuscitation experience curves: simulation based mastery learning
      booster sessions and skill decay patterns among pediatric residents.
AB  - Background Following neonatal resuscitation program (NRP) training, decay in
      clinical skills can occur. Simulation-based deliberate practice (SBDP) has been
      shown to maintain NRP skills to a variable extent. Our study objectives were (a)
      to determine whether a single 30 min simulation-based intervention that
      incorporates SBDP and mastery learning (ML) can effectively restore skills and
      prevent skill decay and (b) to compare different timing options. Methods
      Following NRP certification, pediatric residents were randomly assigned to
      receive a video-recorded baseline assessment plus SBDP-ML refresher education at
      between 6 and 9 months (early) or between 9 and 12 months (late). One year
      following initial certification, participants had repeat skill retention
      videotaped evaluations. Participants were scored by blinded NRP instructors using
      validated criteria scoring tools and assigned a global performance rating score
      (GRS). Results Twenty-seven participants were included. Residents in both early
      and late groups showed significant skill decay 7 and 10 months after initial NRP.
      SBDP-ML booster sessions significantly improved participants' immediate NRP
      performance scores (p<0.001), which persisted for 2 months, but were again lower
      4 months later. Conclusions NRP skills may be boosted to mastery levels after a
      short SBDP-ML intervention and do not appear to significantly decline after 2
      months. Brief booster training could potentially serve as a useful supplement to
      traditional NRP training for pediatric residents.

PMID- 29451863
TI  - Efficacy of three different regimens in recovery of bowel function following
      elective cesarean section: a randomized trial.

PMID- 29451864
TI  - Congenital Zika syndrome in non-endemic regions.

PMID- 29451865
TI  - Flavonoids and triterpenes from Combretum fragrans with anti-inflammatory,
      antioxidant and antidiabetic potential.
AB  - Despite the well-documented benefits of Combretum fragrans in Cameroon, only few
      scientific works have been done on it. In this study we isolated eight compounds
      from the leaves extract of C. fragrans: velutin (1), belamcanidin (2),
      cirsilineol (3), cirsimaritin (4), 3beta-acetoxy-20,24-epoxy-11,25-hydroxy
      dammarane (5), combretin A (6), combretin B (7) and a mixture of arjunolic acid
      (8a) and asiatic acid (8b). Compounds 6 and 7 presented potent anti-inflammatory,
      antioxidant and antidiabetic activities. Compounds 1, 3, 5 and the mixture of 8a
      and 8b were significantly active, and compounds 2 and 4 presented moderate
      activity for reactive oxygen species inhibitory and free-radical scavenging. All
      compounds were isolated using chromatographic techniques; their structures were
      elucidated by spectroscopic techniques and their spectroscopic data compared with
      those of the literature. Anti-inflammatory activity was evaluated via the
      oxidative burst assay using a luminol-amplified chemiluminescence technique,
      antioxidant activity by free-radical scavenging activity (DPPH) and antidiabetic
      activity via alpha-glucosidase inhibition. All of the isolated compounds (1-8)
      were reported to exhibit significant antioxidant activity. Compounds 1, 3, and 5
      8 exhibited potent chemiluminescence inhibition effect, and only compounds 6 and
      7 inhibited alpha-glucosidase. Thus, C. fragrans can be used as an effective
      natural source of anti-inflammatory, antioxidant and antidiabetic compounds.

PMID- 29451866
TI  - High mobility In0.75Ga0.25As quantum wells in an InAs phonon lattice.
AB  - InGaAs based devices are great complements to silicon for CMOS, as they provide
      an increased carrier saturation velocity, lower operating voltage and reduced
      power dissipation (International technology roadmap for semiconductors
      (www.itrs2.net)). In this work we show that In0.75Ga0.25As quantum wells with a
      high mobility, 15 000 to 20 000 cm2 V-1 s-1 at ambient temperature, show an InAs
      like phonon with an energy of 28.8 meV, frequency of 232 cm-1 that dominates the
      polar-optical mode scattering from  ~70 K to 300 K. The measured optical phonon
      frequency is insensitive to the carrier density modulated with a surface gate or
      LED illumination. We model the electron scattering mechanisms as a function of
      temperature and identify mechanisms that limit the electron mobility in
      In0.75Ga0.25As quantum wells. Background impurity scattering starts to dominate
      for temperatures  <100 K. In the high mobility In0.75Ga0.25As quantum well, GaAs
      like phonons do not couple to the electron gas unlike the case of In0.53Ga0.47As
      quantum wells.

PMID- 29451867
TI  - Determination of Debye temperatures and Lamb-Mossbauer factors for LnFeO3
      orthoferrite perovskites (Ln  =  La, Nd, Sm, Eu, Gd).
AB  - Lanthanide orthoferrites have wide-ranging industrial uses including solar,
      catalytic and electronic applications. Here a series of lanthanide orthoferrite
      perovskites, LnFeO3 (Ln  =  La; Nd; Sm; Eu; Gd), prepared through a standard
      stoichiometric wet ball milling route using oxide precursors, has been studied.
      Characterisation through x-ray diffraction and x-ray fluorescence confirmed the
      synthesis of phase-pure or near-pure LnFeO3 compounds. 57Fe Mossbauer
      spectroscopy was performed over a temperature range of 10 K-293 K to observe
      hyperfine structure and to enable calculation of the recoil-free fraction and
      Debye temperature (theta D) of each orthoferrite. Debye temperatures (Ln  =  La
      474 K; Nd 459 K; Sm 457 K; Eu 452 K; Gd 473 K) and recoil-free fractions (Ln  = 
      La 0.827; Nd 0.817; Sm 0.816; Eu 0.812; Gd 0.826) were approximated through
      minimising the difference in the temperature dependent experimental centre shift
      and theoretical isomer shift, by allowing the Debye temperature and isomer shift
      values to vary. This method of minimising the difference between theoretical and
      actual values yields Debye temperatures consistent with results from other
      studies determined through thermal analysis methods. This displays the ability of
      variable-temperature Mossbauer spectroscopy to approximate Debye temperatures and
      recoil-free fractions, whilst observing temperature induced transitions over the
      temperature range observed. X-ray diffraction and Rietveld refinement show an
      inverse relationship between FeO6 octahedral volume and approximated Debye
      temperatures. Raman spectroscopy show an increase in the band positions
      attributed to soft modes of Ag symmetry, Ag(3) and Ag(5) from La to GdFeO3
      corresponding to octahedral rotations and tilts in the [0 1 0] and [1 0 1] planes
      respectively.

PMID- 29451868
TI  - Suppression of material transfer at contacting surfaces: the effect of adsorbates
      on Al/TiN and Cu/diamond interfaces from first-principles calculations.
AB  - The effect of monolayers of oxygen (O) and hydrogen (H) on the possibility of
      material transfer at aluminium/titanium nitride (Al/TiN) and copper/diamond
      (Cu/Cdia) interfaces, respectively, were investigated within the framework of
      density functional theory (DFT). To this end the approach, contact, and
      subsequent separation of two atomically flat surfaces consisting of the
      aforementioned pairs of materials were simulated. These calculations were
      performed for the clean as well as oxygenated and hydrogenated Al and Cdia
      surfaces, respectively. Various contact configurations were considered by
      studying several lateral arrangements of the involved surfaces at the interface.
      Material transfer is typically possible at interfaces between the investigated
      clean surfaces; however, the addition of O to the Al and H to the Cdia surfaces
      was found to hinder material transfer. This passivation occurs because of a
      significant reduction of the adhesion energy at the examined interfaces, which
      can be explained by the distinct bonding situations.

PMID- 29451869
TI  - Use of an Alternating Inflatable Head Pad inPatients Undergoing Open Heart
      Surgery.
AB  - BACKGROUND Preoperative symptoms like occipital pressure ulcers and alopecia
      areata (AA) significantly lowered patient quality of life. Therefore,
      preoperative nursing was in need of investigation. This study aimed to compare
      effects of an alternating inflatable head pad and a gel pad on occurrence of
      postoperative pressure ulcers and AA in patients undergoing open heart surgery.
      MATERIAL AND METHODS This was a prospective study. We allocated randomly 120
      patients undergoing surgery (3-7 h) in the Yantai Yuhuangding Hospital affiliated
      to Qingdao University, China from January to October 2015 to the control (gel
      head pad) or the experimental (alternating inflatable head pad) group (n=60 per
      group). The incidence and severity of occipital pressure ulcer were graded by the
      classification system of the European Pressure Ulcer Advisory Panel (EPUAP). The
      degree of occipital alopecia was measured by hair pull test. This study used the
      t test and chi-square analysis. All statistics were analyzed by SPSS 21.0.
      RESULTS Compared with the control group, there was a significantly lower
      incidence and severity of occipital pressure ulcer and alopecia in the
      experimental group (9 cases/60 cases vs. 1 case/60 cases, P<0.01). Moreover,
      multivariate analysis showed the risk of developing occipital pressure ulcer
      after surgery was also obviously lower in the experimental group (OR 1.449
      120.798; P<0.005). Hair pull test revealed that fewer patients in the
      experimental group had a hair loss over 10%. CONCLUSIONS The alternating
      inflatable head pad was effective in reducing the incidence and severity of
      occipital pressure ulcer and alopecia associated with surgery, which benefited
      the postoperative nursing and improved patient quality of life.

PMID- 29451870
TI  - Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV
      1 infected patients with undetectable viral load.
AB  - INTRODUCTION: A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine
      (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors.
      However, data on use of this combination as a strategy of switch are limited.
      Aims of the study were to assess the long-term efficacy and safety of this
      regimen. METHODS: Retrospective study on HIV-1 infected patients followed at the
      Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg
      negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC,
      with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to
      September 2015. The primary outcome was durability [no treatment failure (TF)].
      Secondary objectives were to evaluate changes in immunological, metabolic and
      other safety parameters. TF was defined as the occurrence of virological failure
      (VF, 2 consecutive values >50 copies/mL) or discontinuation of any drug in the
      regimen for any reason. Patients' follow-up accrued from the date of RPV plus
      ABC/3TC initiation to the date of TF (VF or discontinuation of any drug in the
      regimen) or to the date of last available visit. Time to TF was evaluated by use
      of the Kaplan-Meier curves. Mixed linear models were applied to evaluate changes
      in immunological, metabolic and other safety parameters. RESULTS AND DISCUSSION:
      In this analysis, 100 patients starting RPV plus ABC/3TC were included. By 12, 24
      and 36 months after switching to RPV plus ABC/3TC, the proportions of individuals
      without TF were 88% [95% confidence interval (CI): 79%-93%], 82% (95% CI:73%-89%)
      and 78% (95% CI:68%-86%), respectively. Time to TF was not significantly
      influenced by CD4+ nadir (<=200 vs >200 cells/MUl; log-rank test: p = 0.311) or
      pre-ART viral load (<100000 vs >=100000 copies/mL; log-rank test: p = 0.574) or
      the type of previous antiretroviral regimen (PI+2NRTIs vs NNRTI+2NRTIs vs Other;
      log-rank test: p = 0.942). Over a median follow-up of 2.9 years (IQR: 1.9-3.5),
      26 subjects discontinued the treatment [10 due to toxicity, 7 for interactions
      with other drugs, 3 due to cardiovascular risk concern, 2 due to single viral
      blip, 1 due to VF, 1 for asthma, 1 patient's decision, 1 due to enrolment in a
      study protocol]. CONCLUSIONS: In this retrospective study, long-term use of RPV
      plus ABC/3TC regimen is effective and safe. Efficacy of this regimen was not
      found to be affected by low CD4+ nadir or high pre-ART viral load.

PMID- 29451871
TI  - Environmental heterogeneity blurs the signature of dispersal syndromes on spatial
      patterns of woody species in a moist tropical forest.
AB  - We assessed the relative importance of dispersal limitation, environmental
      heterogeneity and their joint effects as determinants of the spatial patterns of
      229 species in the moist tropical forest of Barro Colorado Island (Panama). We
      differentiated five types of species according to their dispersal syndrome;
      autochorous, anemochorous, and zoochorous species with small, medium-size and
      large fruits. We characterized the spatial patterns of each species and we
      checked whether they were best fitted by Inhomogeneous Poisson (IPP), Homogeneous
      Poisson cluster (HPCP) and Inhomogeneous Poisson cluster processes (IPCP) by
      means of the Akaike Information Criterion. We also assessed the influence of
      species' dispersal mode in the average cluster size. We found that 63% of the
      species were best fitted by IPCP regardless of their dispersal syndrome, although
      anemochorous species were best described by HPCP. Our results indicate that
      spatial patterns of tree species in this forest cannot be explained only by
      dispersal limitation, but by the joint effects of dispersal limitation and
      environmental heterogeneity. The absence of relationships between dispersal mode
      and degree of clustering suggests that several processes modify the original
      spatial pattern generated by seed dispersal. These findings emphasize the
      importance of fitting point process models with a different biological meaning
      when studying the main determinants of spatial structure in plant communities.

PMID- 29451872
TI  - Differences in neural responses to ipsilateral stimuli in wide-view fields
      between face- and house-selective areas.
AB  - Category-selective brain areas exhibit varying levels of neural activity to
      ipsilaterally presented stimuli. However, in face- and house-selective areas, the
      neural responses evoked by ipsilateral stimuli in the peripheral visual field
      remain unclear. In this study, we displayed face and house images using a wide
      view visual presentation system while performing functional magnetic resonance
      imaging (fMRI). The face-selective areas (fusiform face area (FFA) and occipital
      face area (OFA)) exhibited intense neural responses to ipsilaterally presented
      images, whereas the house-selective areas (parahippocampal place area (PPA) and
      transverse occipital sulcus (TOS)) exhibited substantially smaller and even
      negative neural responses to the ipsilaterally presented images. We also found
      that the category preferences of the contralateral and ipsilateral neural
      responses were similar. Interestingly, the face- and house-selective areas
      exhibited neural responses to ipsilateral images that were smaller than the
      responses to the contralateral images. Multi-voxel pattern analysis (MVPA) was
      implemented to evaluate the difference between the contralateral and ipsilateral
      responses. The classification accuracies were much greater than those expected by
      chance. The classification accuracies in the FFA were smaller than those in the
      PPA and TOS. The closer eccentricities elicited greater classification accuracies
      in the PPA and TOS. We propose that these ipsilateral neural responses might be
      interpreted by interhemispheric communication through intrahemispheric
      connectivity of white matter connection and interhemispheric connectivity via the
      corpus callosum and occipital white matter connection. Furthermore, the PPA and
      TOS likely have weaker interhemispheric communication than the FFA and OFA,
      particularly in the peripheral visual field.

PMID- 29451873
TI  - In silico analysis of antibiotic-induced Clostridium difficile infection:
      Remediation techniques and biological adaptations.
AB  - In this paper we study antibiotic-induced C. difficile infection (CDI), caused by
      the toxin-producing C. difficile (CD), and implement clinically-inspired
      simulated treatments in a computational framework that synthesizes a generalized
      Lotka-Volterra (gLV) model with SIR modeling techniques. The gLV model uses
      parameters derived from an experimental mouse model, in which the mice are
      administered antibiotics and subsequently dosed with CD. We numerically identify
      which of the experimentally measured initial conditions are vulnerable to CD
      colonization, then formalize the notion of CD susceptibility analytically. We
      simulate fecal transplantation, a clinically successful treatment for CDI, and
      discover that both the transplant timing and transplant donor are relevant to the
      the efficacy of the treatment, a result which has clinical implications. We
      incorporate two nongeneric yet dangerous attributes of CD into the gLV model,
      sporulation and antibiotic-resistant mutation, and for each identify relevant SIR
      techniques that describe the desired attribute. Finally, we rely on the results
      of our framework to analyze an experimental study of fecal transplants in mice,
      and are able to explain observed experimental results, validate our simulated
      results, and suggest model-motivated experiments.

PMID- 29451874
TI  - A stochastic and dynamical view of pluripotency in mouse embryonic stem cells.
AB  - Pluripotent embryonic stem cells are of paramount importance for biomedical
      sciences because of their innate ability for self-renewal and differentiation
      into all major cell lines. The fateful decision to exit or remain in the
      pluripotent state is regulated by complex genetic regulatory networks. The rapid
      growth of single-cell sequencing data has greatly stimulated applications of
      statistical and machine learning methods for inferring topologies of pluripotency
      regulating genetic networks. The inferred network topologies, however, often only
      encode Boolean information while remaining silent about the roles of dynamics and
      molecular stochasticity inherent in gene expression. Herein we develop a
      framework for systematically extending Boolean-level network topologies into
      higher resolution models of networks which explicitly account for the promoter
      architectures and gene state switching dynamics. We show the framework to be
      useful for disentangling the various contributions that gene switching, external
      signaling, and network topology make to the global heterogeneity and dynamics of
      transcription factor populations. We find the pluripotent state of the network to
      be a steady state which is robust to global variations of gene switching rates
      which we argue are a good proxy for epigenetic states of individual promoters.
      The temporal dynamics of exiting the pluripotent state, on the other hand, is
      significantly influenced by the rates of genetic switching which makes cells more
      responsive to changes in extracellular signals.

PMID- 29451875
TI  - Linkage to HIV care following diagnosis in the WHO European Region: A systematic
      review and meta-analysis, 2006-2017.
AB  - BACKGROUND: Timely linkage to care after HIV diagnosis is crucial as delayed
      access can result in poor patient outcomes. The aim of this systematic review was
      to synthesise the evidence to achieve a better understanding of what proportion
      of patients are linked to care and what factors impact linkage. METHODS:
      Systematic searches were run in six databases up to the end of February 2017. The
      grey literature was also reviewed. Inclusion criteria were: sample size >=50
      people (aged >=15), from the WHO European Region, published 2006-2017 and in
      English. Linkage to care was defined as a patient seen for HIV care after
      diagnosis. Study selection, data extraction and quality assurance were performed
      by two independent reviewers. Random-effects meta-analysis was carried out to
      summarise linkage to care within three months of diagnosis. RESULTS: Twenty-four
      studies were included; 22 presented linkage to care data and seven examined
      factors for linkage. Linkage among 89,006 people in 19 countries was captured.
      Meta-analysis, restricted to 12 studies and measuring prompt linkage within three
      months, gave a pooled estimate of 85% (95% CI: 75%-93%). Prompt linkage was
      higher in studies including only people in care (94%; 95% CI: 91%-97%) than in
      those of all new diagnoses (71%; 95% CI: 50%-87%). Heterogeneity was high across
      and within strata (>99%). Factors associated with delaying or not linking to care
      included: acquiring HIV through heterosexual contact/injecting drug use, younger
      age at diagnosis, lower levels of education, feeling well at diagnosis and
      diagnosis outside an STI clinic. CONCLUSION: Overall, linkage to care was high,
      though estimates were lower in studies with a high proportion of people who
      inject drugs. The high heterogeneity between studies made it challenging to
      synthesise findings. Studies should adopt a standardised definition with a three
      month cut-off to measure prompt linkage to care to ensure comparability.

PMID- 29451877
TI  - Influence of hyperbaric oxygen on biomechanics and structural bone matrix in type
      1 diabetes mellitus rats.
AB  - BACKGROUND: The aim of this study was to evaluate the biomechanics and structural
      bone matrix in diabetic rats subjected to hyperbaric oxygen therapy (HBO).
      METHODS: Twenty-four male rats were divided into the following groups: Control;
      Control + HBO; Diabetic, and Diabetic + HBO. Diabetes was induced with
      streptozotocin (STZ) in the diabetic Groups. After 30 days, HBO was performed
      every 48h in HBO groups and all animals were euthanized 60 days after diabetic
      induction. The femur was submitted to a biomechanical (maximum strength, energy
      to-failure and stiffness) and Attenuated Total Reflectance Fourier transform
      infrared (ATR-FTIR) analyses (crosslink ratio, crystallinity index, matrix-to
      mineral ratio: Amide I + II/Hydroxyapatite (M:MI) and Amide III + Collagen/HA
      (M:MIII)). RESULTS: In biomechanical analysis, diabetic animals showed lower
      values of maximum strength, energy and stiffness than non-diabetic animals.
      However, structural strength and stiffness were increased in groups with HBO
      compared with non-HBO. ATR-FTIR analysis showed decreased collagen maturity in
      the ratio of crosslink peaks in diabetic compared with the other groups. The bone
      from the diabetic groups showed decreased crystallinity compared with non
      diabetic groups. M:MI showed no statistical difference between groups. However,
      M:MIII showed an increased matrix mineral ratio in diabetic+HBO and control+HBO
      compared with control and diabetic groups. Correlations between mechanical and
      ATR-FTIR analyses showed significant positive correlation between collagen
      maturity and stiffness. CONCLUSIONS: Diabetes decreased collagen maturation and
      the mineral deposition process, thus reducing biomechanical properties. Moreover,
      the study showed that HBO improved crosslink maturation and increased maximum
      strength and stiffness in the femur of T1DM animals.

PMID- 29451876
TI  - Comparative genomic analysis of the multispecies probiotic-marketed product
      VSL#3.
AB  - Several probiotic-marketed formulations available for the consumers contain live
      lactic acid bacteria and/or bifidobacteria. The multispecies product
      commercialized as VSL#3 has been used for treating various gastro-intestinal
      disorders. However, like many other products, the bacterial strains present in
      VSL#3 have only been characterized to a limited extent and their efficacy as well
      as their predicted mode of action remain unclear, preventing further applications
      or comparative studies. In this work, the genomes of all eight bacterial strains
      present in VSL#3 were sequenced and characterized, to advance insights into the
      possible mode of action of this product and also to serve as a basis for future
      work and trials. Phylogenetic and genomic data analysis allowed us to identify
      the 7 species present in the VSL#3 product as specified by the manufacturer. The
      8 strains present belong to the species Streptococcus thermophilus, Lactobacillus
      acidophilus, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus
      helveticus, Bifidobacterium breve and B. animalis subsp. lactis (two distinct
      strains). Comparative genomics revealed that the draft genomes of the S.
      thermophilus and L. helveticus strains were predicted to encode most of the
      defence systems such as restriction modification and CRISPR-Cas systems. Genes
      associated with a variety of potential probiotic functions were also identified.
      Thus, in the three Bifidobacterium spp., gene clusters were predicted to encode
      tight adherence pili, known to promote bacteria-host interaction and intestinal
      barrier integrity, and to impact host cell development. Various repertoires of
      putative signalling proteins were predicted to be encoded by the genomes of the
      Lactobacillus spp., i.e. surface layer proteins, LPXTG-containing proteins, or
      sortase-dependent pili that may interact with the intestinal mucosa and dendritic
      cells. Taken altogether, the individual genomic characterization of the strains
      present in the VSL#3 product confirmed the product specifications, determined its
      coding capacity as well as identified potential probiotic functions.

PMID- 29451878
TI  - Control fast or control smart: When should invading pathogens be controlled?
AB  - The intuitive response to an invading pathogen is to start disease management as
      rapidly as possible, since this would be expected to minimise the future impacts
      of disease. However, since more spread data become available as an outbreak
      unfolds, processes underpinning pathogen transmission can almost always be
      characterised more precisely later in epidemics. This allows the future
      progression of any outbreak to be forecast more accurately, and so enables
      control interventions to be targeted more precisely. There is also the chance
      that the outbreak might die out without any intervention whatsoever, making
      prophylactic control unnecessary. Optimal decision-making involves continuously
      balancing these potential benefits of waiting against the possible costs of
      further spread. We introduce a generic, extensible data-driven algorithm based on
      parameter estimation and outbreak simulation for making decisions in real-time
      concerning when and how to control an invading pathogen. The Control Smart
      Algorithm (CSA) resolves the trade-off between the competing advantages of
      controlling as soon as possible and controlling later when more information has
      become available. We show-using a generic mathematical model representing the
      transmission of a pathogen of agricultural animals or plants through a population
      of farms or fields-how the CSA allows the timing and level of deployment of
      vaccination or chemical control to be optimised. In particular, the algorithm
      outperforms simpler strategies such as intervening when the outbreak size reaches
      a pre-specified threshold, or controlling when the outbreak has persisted for a
      threshold length of time. This remains the case even if the simpler methods are
      fully optimised in advance. Our work highlights the potential benefits of giving
      careful consideration to the question of when to start disease management during
      emerging outbreaks, and provides a concrete framework to allow policy-makers to
      make this decision.

PMID- 29451879
TI  - Dengue knowledge, attitudes and practices and their impact on community-based
      vector control in rural Cambodia.
AB  - BACKGROUND: Globally there are an estimated 390 million dengue infections per
      year, of which 96 million are clinically apparent. In Cambodia, estimates suggest
      as many as 185,850 cases annually. The World Health Organization global strategy
      for dengue prevention aims to reduce mortality rates by 50% and morbidity by 25%
      by 2020. The adoption of integrated vector management approach using community
      based methods tailored to the local context is one of the recommended strategies
      to achieve these objectives. Understanding local knowledge, attitudes and
      practices is therefore essential to designing suitable strategies to fit each
      local context. METHODS AND FINDINGS: A Knowledge, Attitudes and Practices survey
      in 600 randomly chosen households was administered in 30 villages in Kampong Cham
      which is one of the most populated provinces of Cambodia. KAP surveys were
      administered to a sub-sample of households where an entomology survey was
      conducted (1200 households), during which Aedes larval/pupae and adult female
      Aedes mosquito densities were recorded. Participants had high levels of knowledge
      regarding the transmission of dengue, Aedes breeding, and biting prevention
      methods; the majority of participants believed they were at risk and that dengue
      transmission is preventable. However, self-reported vector control practices did
      not match observed practices recorded in our surveys. No correlation was found
      between knowledge and observed practices either. CONCLUSION: An education
      campaign regarding dengue prevention in this setting with high knowledge levels
      is unlikely to have any significant effect on practices unless it is incorporated
      in a more comprehensive strategy for behavioural change, such a COMBI method,
      which includes behavioural models as well as communication and marketing theory
      and practice. TRIAL REGISTRATION: ISRCTN85307778.

PMID- 29451880
TI  - Apolipoprotein E genotype does not moderate the associations of depressive
      symptoms, neuroticism and allostatic load with cognitive ability and cognitive
      aging in the Lothian Birth Cohort 1936.
AB  - OBJECTIVES: In this replication-and-extension study, we tested whether depressive
      symptoms, neuroticism, and allostatic load (multisystem physiological
      dysregulation) were related to lower baseline cognitive ability and greater
      subsequent cognitive decline in older adults, and whether these relationships
      were moderated by the E4 allele of the apolipoprotein E (APOE) gene. We also
      tested whether allostatic load mediated the relationships between neuroticism and
      cognitive outcomes. METHODS: We used data from the Lothian Birth Cohort 1936 (n
      at Waves 1-3: 1,028 [M age = 69.5 y]; 820 [M duration since Wave 1 = 2.98 y]; 659
      [M duration since Wave 1 = 6.74 y]). We fitted latent growth curve models of
      general cognitive ability (modeled using five cognitive tests) with groups of
      APOE E4 non-carriers and carriers. In separate models, depressive symptoms,
      neuroticism, and allostatic load predicted baseline cognitive ability and
      subsequent cognitive decline. In addition, models tested whether allostatic load
      mediated relationships between neuroticism and cognitive outcomes. RESULTS:
      Baseline cognitive ability had small-to-moderate negative associations with
      depressive symptoms (beta range = -0.20 to -0.17), neuroticism (beta range = 
      0.27 to -0.23), and allostatic load (beta range = -0.11 to 0.09). Greater
      cognitive decline was linked to baseline allostatic load (beta range = -0.98 to 
      0.83) and depressive symptoms (beta range = -1.00 to -0.88). However, APOE E4
      allele possession did not moderate the relationships of depressive symptoms,
      neuroticism and allostatic load with cognitive ability and cognitive decline.
      Additionally, the associations of neuroticism with cognitive ability and
      cognitive decline were not mediated through allostatic load. CONCLUSIONS: Our
      results suggest that APOE E4 status does not moderate the relationships of
      depressive symptoms, neuroticism, and allostatic load with cognitive ability and
      cognitive decline in healthy older adults. The most notable positive finding in
      the current research was the strong association between allostatic load and
      cognitive decline.

PMID- 29451881
TI  - Population-based coverage survey results following the mass drug administration
      of azithromycin for the treatment of trachoma in Amhara, Ethiopia.
AB  - BACKGROUND: Trachoma is the leading infectious cause of blindness worldwide. In
      communities where the district level prevalence of trachomatous inflammation
      follicular among children ages 1-9 years is >=5%, WHO recommends annual mass drug
      administration (MDA) of antibiotics with the aim of at least 80% coverage.
      Population-based post-MDA coverage surveys are essential to understand the
      effectiveness of MDA programs, yet published reports from trachoma programs are
      rare. METHODS: In the Amhara region of Ethiopia, a population-based MDA coverage
      survey was conducted 3 weeks following the 2016 MDA to estimate the zonal
      prevalence of self-reported drug coverage in all 10 administrative zones. Survey
      households were selected using a multi-stage cluster random sampling design and
      all individuals in selected households were presented with a drug sample and
      asked about taking the drug during the campaign. Zonal estimates were weighted
      and confidence intervals were calculated using survey procedures. Self-reported
      drug coverage was then compared with regional reported administrative coverage.
      RESULTS: Region-wide, 24,248 individuals were enumerated, of which, 20,942
      (86.4%) individuals were present. The regional self-reported antibiotic coverage
      was 76.8% (95%Confidence Interval (CI):69.3-82.9%) in the population overall and
      77.4% (95%CI = 65.7-85.9%) among children ages 1-9 years old. Zonal coverage
      ranged from 67.8% to 90.2%. Five out of 10 zones achieved a coverage >80%. In all
      zones, the reported administrative coverage was greater than 90% and was
      considerably higher than self-reported MDA coverage. Main reasons reported for
      MDA campaign non-attendance included being physically unable to get to MDA site
      (22.5%), traveling (20.6%), and not knowing about the campaign (21.0%). MDA
      refusal was low (2.8%) in this population. CONCLUSIONS: Although self-reported
      MDA coverage in Amhara was greater than 80% in some zones, programmatic
      improvements are warranted throughout Amhara to achieve higher coverage. These
      results will be used to enhance community mobilization and improve training for
      MDA distributors and supervisors to improve coverage in future MDAs.

PMID- 29451882
TI  - De novo transcriptomic analysis of leaf and fruit tissue of Cornus officinalis
      using Illumina platform.
AB  - Cornus officinalis is one of the most widely used medicinal plants in China and
      other East Asian countries to cure diseases such as liver, kidney, cardiovascular
      diseases and frequent urination for thousands of years. It is a Level 3 protected
      species, and is one of the 42 national key protected wild species of animals and
      plants in China. However, the genetics and molecular biology of C. officinalis
      are poorly understood, which has hindered research on the molecular mechanism of
      its metabolism and utilization. Hence, enriching its genomic data and information
      is very important. In recent years, the fast-growing technology of next
      generation sequencing has provided an effective path to gain genomic information
      from nonmodel species. This study is the first to explore the leaf and fruit
      tissue transcriptome of C. officinalis using the Illumina HiSeq 4000 platform. A
      total of 57,954,134 and 60,971,652 clean reads from leaf and fruit were acquired,
      respectively (GenBank number SRP115440). The pooled reads from all two libraries
      were assembled into 56,392 unigenes with an average length 856 bp. Among these,
      41,146 unigenes matched with sequences in the NCBI nonredundant protein database.
      The Gene Ontology database assigned 24,336 unigenes with biological process
      (83.26%), cellular components (53.58%), and molecular function (83.93%). In
      addition, 10,808 unigenes were assigned a KOG functional classification by the
      KOG database. Searching against the KEGG pathway database indicated that 18,435
      unigenes were mapped to 371 KEGG pathways. Moreover, the edgeR database
      identified 4,585 significant differentially expressed genes (DEGs), of which
      1,392 were up-regulated and 3,193 were down-regulated in fruit tissue compared
      with leaf tissue. Finally, we explored 581 transcription factors with 50
      transcription factor gene families. Most DEGs and transcription factors were
      related to terpene biosynthesis and secondary metabolic regulation. This study
      not only represented the first de novo transcriptomic analysis of C. officinalis
      but also provided fundamental information on its genes and biosynthetic pathway.
      These findings will help us explore the molecular metabolism mechanism of terpene
      biosynthesis in C. officinalis.

PMID- 29451883
TI  - Management of post abortion complications in Botswana -The need for a
      standardized approach.
AB  - BACKGROUND: Post abortion complications are the third leading cause of maternal
      death after hemorrhage and hypertension in Botswana where abortion is not
      legalized. This study aimed at assessing the management of post abortion
      complications in Botswana. METHODS: A retrospective study was conducted at four
      hospitals in Botswana in 2014. Socio-demographic, patient management and outcomes
      data were extracted from patients' medical records. Descriptive statistics and
      chi-square test were used to analyze and present the data. RESULT: A total of 619
      patients' medical records were reviewed. The duration of hospital stay prior to
      uterine evacuation ranged from less than an hour to 480 hours. All the patients
      received either prophylactic or therapeutic antibiotics. Use of parenteral
      antibiotics was significantly associated with severity of abortion, second
      trimester abortion, use of blood products and the interval between management's
      decision and uterine evacuation. Uterine evacuation for retained products of
      conception was achieved by metallic curettage among 516 (83.4%) patients and by
      vacuum aspiration in 18 (2.9%). At all the study sites, Misoprostol or Oxytocin
      were used concurrently with surgical evacuation of the uterus. None use of
      analgesics or anesthetics in the four hospitals ranged between 12.4% to 28.8%.
      CONCLUSION: There is evidence of delayed patient care and prolonged hospital
      stay. Metallic curette was the primary method used for uterine evacuation across
      all the facilities. Pain management and antibiotics use was not standardized. A
      protocol has to be developed with the aim of standardizing post abortion care.

PMID- 29451884
TI  - A damped oscillator imposes temporal order on posterior gap gene expression in
      Drosophila.
AB  - Insects determine their body segments in two different ways. Short-germband
      insects, such as the flour beetle Tribolium castaneum, use a molecular clock to
      establish segments sequentially. In contrast, long-germband insects, such as the
      vinegar fly Drosophila melanogaster, determine all segments simultaneously
      through a hierarchical cascade of gene regulation. Gap genes constitute the first
      layer of the Drosophila segmentation gene hierarchy, downstream of maternal
      gradients such as that of Caudal (Cad). We use data-driven mathematical modelling
      and phase space analysis to show that shifting gap domains in the posterior half
      of the Drosophila embryo are an emergent property of a robust damped oscillator
      mechanism, suggesting that the regulatory dynamics underlying long- and short
      germband segmentation are much more similar than previously thought. In
      Tribolium, Cad has been proposed to modulate the frequency of the segmentation
      oscillator. Surprisingly, our simulations and experiments show that the shift
      rate of posterior gap domains is independent of maternal Cad levels in
      Drosophila. Our results suggest a novel evolutionary scenario for the short- to
      long-germband transition and help explain why this transition occurred
      convergently multiple times during the radiation of the holometabolan insects.

PMID- 29451885
TI  - Repeated stimulation, inter-stimulus interval and inter-electrode distance alters
      muscle contractile properties as measured by Tensiomyography.
AB  - CONTEXT: The influence of methodological parameters on the measurement of muscle
      contractile properties using Tensiomyography (TMG) has not been published.
      OBJECTIVE: To investigate the; (1) reliability of stimulus amplitude needed to
      elicit maximum muscle displacement (Dm), (2) effect of changing inter-stimulus
      interval on Dm (using a fixed stimulus amplitude) and contraction time (Tc), (3)
      the effect of changing inter-electrode distance on Dm and Tc. DESIGN: Within
      subject, repeated measures. PARTICIPANTS: 10 participants for each objective.
      MAIN OUTCOME MEASURES: Dm and Tc of the rectus femoris, measured using TMG.
      RESULTS: The coefficient of variance (CV) and the intra-class correlation (ICC)
      of stimulus amplitude needed to elicit maximum Dm was 5.7% and 0.92 respectively.
      Dm was higher when using an inter-electrode distance of 7cm compared to 5cm [P =
      0.03] and when using an inter-stimulus interval of 10s compared to 30s [P =
      0.017]. Further analysis of inter-stimulus interval data, found that during 10
      repeated stimuli Tc became faster after the 5th measure when compared to the
      second measure [P<0.05]. The 30s inter-stimulus interval produced the most stable
      Tc over 10 measures compared to 10s and 5s respectively. CONCLUSION: Our data
      suggest that the stimulus amplitude producing maximum Dm of the rectus femoris is
      reliable. Inter-electrode distance and inter-stimulus interval can significantly
      influence Dm and/ or Tc. Our results support the use of a 30s inter-stimulus
      interval over 10s or 5s. Future studies should determine the influence of
      methodological parameters on muscle contractile properties in a range of muscles.

PMID- 29451886
TI  - Which preferences associate with school performance?-Lessons from an exploratory
      study with university students.
AB  - Success in life is determined to a large extent by school performance so it is
      important to understand the effect of the factors that influence it. In this
      exploratory study, in addition to cognitive abilities, we attempt to link
      measures of preferences with outcomes of school performance. We measured in an
      incentivized way risk, time, social and competitive preferences and cognitive
      abilities of university students to look for associations between these measures
      and two important academic outcome measures: exam results and GPA. We find
      consistently that cognitive abilities (proxied by the Cognitive Reflection Test)
      are very well correlated with school performance. Regarding non-cognitive skills,
      we report suggestive evidence for many of our measured preferences. We used two
      alternative measures of time preference: patience and present bias. Present bias
      explains exam grades better, while patience explains GPA relatively better. Both
      measures of time preferences have a non-linear relation to school performance.
      Competitiveness matters, as students, who opt for a more competitive payment
      scheme in our experimental task have a higher average GPA. We observe also that
      risk-averse students perform a little better than more risk-tolerant students.
      That makes sense in case of multiple choice exams, because more risk-tolerant
      students may want to try to pass the exam less prepared, as the possibility of
      passing an exam just by chance is not zero. Finally, we have also detected that
      cooperative preferences-the amount of money offered in a public good game
      associates strongly with GPA in a non-linear way. Students who offered around
      half of their possible amounts had significantly higher GPAs than those, who
      offered none or all their money.

PMID- 29451888
TI  - Ecogeography of teosinte.
AB  - Adaptation of crops to climate change has motivated an increasing interest in the
      potential value of novel traits from wild species; maize wild relatives, the
      teosintes, harbor traits that may be useful to maize breeding. To study the
      ecogeographic distribution of teosinte we constructed a robust database of 2363
      teosinte occurrences from published sources for the period 1842-2016. A
      geographical information system integrating 216 environmental variables was
      created for Mexico and Central America and was used to characterize the
      environment of each teosinte occurrence site. The natural geographic distribution
      of teosinte extends from the Western Sierra Madre of the State of Chihuahua,
      Mexico to the Pacific coast of Nicaragua and Costa Rica, including practically
      the entire western part of Mesoamerica. The Mexican annuals Zea mays ssp.
      parviglumis and Zea mays ssp. mexicana show a wide distribution in Mexico, while
      Zea diploperennis, Zea luxurians, Zea perennis, Zea mays ssp. huehuetenangensis,
      Zea vespertilio and Zea nicaraguensis had more restricted and distinct ranges,
      representing less than 20% of the total occurrences. Only 11.2% of teosinte
      populations are found in Protected Natural Areas in Mexico and Central America.
      Ecogeographical analysis showed that teosinte can cope with extreme levels of
      precipitation and temperatures during growing season. Modelling teosinte
      geographic distribution demonstrated congruence between actual and potential
      distributions; however, some areas with no occurrences appear to be within the
      range of adaptation of teosintes. Field surveys should be prioritized to such
      regions to accelerate the discovery of unknown populations. Potential areas for
      teosintes Zea mays ssp. mexicana races Chalco, Nobogame, and Durango, Zea mays
      ssp. huehuetenangensis, Zea luxurians, Zea diploperennis and Zea nicaraguensis
      are geographically separated; however, partial overlapping occurs between Zea
      mays ssp. parviglumis and Zea perennis, between Zea mays ssp. parviglumis and Zea
      diploperennis, and between Zea mays ssp. mexicana race Chalco and Zea mays ssp.
      mexicana race Central Plateau. Assessing priority of collecting for conservation
      showed that permanent monitoring programs and in-situ conservation projects with
      participation of local farmer communities are critically needed; Zea mays ssp.
      mexicana (races Durango and Nobogame), Zea luxurians, Zea diploperennis, Zea
      perennis and Zea vespertilio should be considered as the highest priority taxa.

PMID- 29451887
TI  - Evaluating diagnostic indicators of urogenital Schistosoma haematobium infection
      in young women: A cross sectional study in rural South Africa.
AB  - BACKGROUND: Urine microscopy is the standard diagnostic method for urogenital S.
      haematobium infection. However, this may lead to under-diagnosis of urogenital
      schistosomiasis, as the disease may present itself with genital symptoms in the
      absence of ova in the urine. Currently there is no single reliable and affordable
      diagnostic method to diagnose the full spectrum of urogenital S. haematobium
      infection. In this study we explore the classic indicators in the diagnosis of
      urogenital S. haematobium infection, with focus on young women. METHODS: In a
      cross-sectional study of 1237 sexually active young women in rural South Africa,
      we assessed four diagnostic indicators of urogenital S. haematobium infection:
      microscopy of urine, polymerase chain reaction (PCR) of cervicovaginal lavage
      (CVL), urogenital symptoms, and sandy patches detected clinically in combination
      with computerised image analysis of photocolposcopic images. We estimated the
      accuracy of these diagnostic indicators through the following analyses: 1) cross
      tabulation (assumed empirical gold standard) of the tests against the combined
      findings of sandy patches and/or computerized image analysis and 2) a latent
      class model of the four indicators without assuming any gold standard. RESULTS:
      The empirical approach showed that urine microscopy had a sensitivity of 34.7%
      and specificity of 75.2% while the latent class analysis approach (LCA) suggested
      a sensitivity of 81.0% and specificity of 85.6%. The empirical approach and LCA
      showed that Schistosoma PCR in CVL had low sensitivity (14.1% and 52.4%,
      respectively) and high specificity (93.0% and 98.0, respectively). Using LCA, the
      presence of sandy patches showed a sensitivity of 81.6 and specificity of 42.4%.
      The empirical approach and LCA showed that urogenital symptoms had a high
      sensitivity (89.4% and 100.0%, respectively), whereas specificity was low (10.6%
      and 12.3%, respectively). CONCLUSION: All the diagnostic indicators used in the
      study had limited accuracy. Using urine microscopy or Schistosoma PCR in CVL
      would only confirm a fraction of the sandy patches found by colposcopic
      examination.

PMID- 29451890
TI  - Detection of Bartonella spp. in fleas by MALDI-TOF MS.
AB  - BACKGROUND: Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass
      Spectrometry (MALDI-TOF MS) has recently emerged in the field of entomology as a
      promising method for the identification of arthropods and the detection of
      associated pathogens. METHODOLOGY/PRINCIPAL FINDINGS: An experimental model of
      Ctenocephalides felis (cat fleas) infected with Bartonella quintana and
      Bartonella henselae was developed to evaluate the efficacy of MALDI-TOF MS in
      distinguishing infected from uninfected fleas, and its ability to distinguish
      fleas infected with Bartonella quintana from fleas infected with Bartonella
      henselae. For B. quintana, two groups of fleas received three successive blood
      meals, infected or not. A total of 140 fleas (100 exposed fleas and 40 control
      fleas) were engorged on human blood, infected or uninfected with B. quintana.
      Regarding the second pathogen, two groups of fleas (200 exposed fleas and 40
      control fleas) were fed in the same manner with human blood, infected or not with
      Bartonella henselae. Fleas were dissected longitudinally; one-half was used for
      assessment of B. quintana and B. henselae infectious status by real-time PCR, and
      the second half was subjected to MALDI-TOF MS analysis. Comparison of MS spectra
      from infected fleas and uninfected fleas revealed distinct MS profiles. Blind
      queries against our MALDI-TOF MS arthropod database, upgraded with reference
      spectra from B. quintana and B. henselae infected fleas but also non-infected
      fleas, provided the correct classification for 100% of the different categories
      of specimens tested on the first model of flea infection with Bartonella
      quintana. As for Bartonella henselae, 81% of exposed qPCR-positive fleas, 96% of
      exposed qPCR-negative fleas and 100% of control fleas were correctly identified
      on the second model of flea infection. MALDI-TOF MS successfully differentiated
      Bartonella spp.-infected and uninfected fleas and was also able to correctly
      differentiate fleas infected with Bartonella quintana and fleas infected with
      Bartonella henselae. MALDI-TOF MS correctly identified flea species as well as
      their infectious status, consistent with the results of real-time PCR.
      CONCLUSIONS/SIGNIFICANCE: MALDI-TOF is a promising tool for identification of the
      infection status of fleas infected with Bartonella spp., which allows new
      possibilities for fast and accurate diagnosis in medical entomology and vector
      surveillance.

PMID- 29451889
TI  - Effects of patterned peripheral nerve stimulation on soleus spinal motor neuron
      excitability.
AB  - Spinal plasticity is thought to contribute to sensorimotor recovery of limb
      function in several neurological disorders and can be experimentally induced in
      animals and humans using different stimulation protocols. In healthy individuals,
      electrical continuous Theta Burst Stimulation (TBS) of the median nerve has been
      shown to change spinal motoneuron excitability in the cervical spinal cord as
      indexed by a change in mean H-reflex amplitude in the flexor carpi radialis
      muscle. It is unknown whether continuous TBS of a peripheral nerve can also shift
      motoneuron excitability in the lower limb. In 26 healthy subjects, we examined
      the effects of electrical TBS given to the tibial nerve in the popliteal fossa on
      the excitability of lumbar spinal motoneurons as measured by H-reflex amplitude
      of the soleus muscle evoked by tibial nerve stimulation. Continuous TBS was given
      at 110% of H-reflex threshold intensity and compared to non-patterned regular
      electrical stimulation at 15 Hz. To disclose any pain-induced effects, we also
      tested the effects of TBS at individual sensory threshold. Moreover, in a
      subgroup of subjects we evaluated paired-pulse inhibition of H-reflex. Continuous
      TBS at 110% of H-reflex threshold intensity induced a short-term reduction of H
      reflex amplitude. The other stimulation conditions produced no after effects.
      Paired-pulse H-reflex inhibition was not modulated by continuous TBS or non
      patterned repetitive stimulation at 15 Hz. An effect of pain on the results
      obtained was discarded, since non-patterned 15 Hz stimulation at 110% HT led to
      pain scores similar to those induced by EcTBS at 110% HT, but was not able to
      induce any modulation of the H reflex amplitude. Together, the results provide
      first time evidence that peripheral continuous TBS induces a short-lasting change
      in the excitability of spinal motoneurons in lower limb circuitries. Future
      studies need to investigate how the TBS protocol can be optimized to produce a
      larger and longer effect on spinal cord physiology and whether this might be a
      useful intervention in patients with excessive excitability of the spinal
      motorneurons.

PMID- 29451892
TI  - Assessing site formation and assemblage integrity through stone tool refitting at
      Gruta da Oliveira (Almonda karst system, Torres Novas, Portugal): A Middle
      Paleolithic case study.
AB  - We use stone tool refitting to assess palimpsest formation and stratigraphic
      integrity in the basal units of the Gruta da Oliveira archeo-stratigraphic
      sequence, layers 15-27, which TL and U-series dating places in late Marine
      Isotope Stage (MIS) 5 or early MIS 4. As in most karst contexts, the formation of
      this succession involved multiple and complex phenomena, including subsidence,
      bioturbation, carnivore activity and runoff as agents of potential post
      depositional disturbance. During phases of stabilization, such as represented by
      layers 15, 21 and 22, the excavated area was inhabited and refits corroborate
      that post-depositional displacement is negligible. Layers 23-25 and 16-19
      correspond to subdivisions that slice thick geological units primarily formed of
      material derived from the cave's entrance via slope dynamics. Refit links are
      consistent with rapid fill-up of the interstitial spaces found in the Karren-like
      bedrock (for layers 23-25), or left between large boulders after major roof
      collapse events (for layers 16-19). Layers 26 (the "Mousterian Cone") and 27 are
      a "bottom-of-hourglass" deposit underlying the main sedimentary body; the refits
      show that this deposit consists of material derived from layers 15-25 that
      gravitated through fissures open in the sedimentary column above. Layer 20, at
      the interface between two major stratigraphic ensembles, requires additional
      analysis. Throughout, we found significant vertical dispersion along the contact
      between sedimentary fill and cave wall. Given these findings, a preliminary
      analysis of technological change across the studied sequence organized the lithic
      assemblages into five ensembles: layer 15; layers 16-19; layer 20; layers 21-22;
      layers 23-25. The lower ensembles show higher percentages of flint and of the
      Levallois method. Uniquely at the site, the two upper ensembles feature bifaces
      and cleavers.

PMID- 29451891
TI  - Association of an intact E2 gene with higher HPV viral load, higher viral
      oncogene expression, and improved clinical outcome in HPV16 positive head and
      neck squamous cell carcinoma.
AB  - To assess the relationship of E2 gene disruption with viral gene expression and
      clinical outcome in human papillomavirus (HPV) positive head and neck squamous
      cell carcinoma, we evaluated 31 oropharyngeal and 17 non-oropharyngeal HPV16
      positive carcinomas using two PCR-based methods to test for disruption of E2,
      followed by Sanger sequencing. Expression of HPV16 E6, E7 and E2 transcripts,
      along with cellular ARF and INK4A, were also assessed by RT-qPCR. Associations
      between E2 disruption, E2/E6/E7 expression, and clinical outcome were evaluated
      by Kaplan-Meier analysis for loco-regional recurrence and disease-specific
      survival. The majority (n = 21, 68%) of HPV16 positive oropharyngeal carcinomas
      had an intact E2 gene, whereas the majority of HPV16 positive non-oropharyngeal
      carcinomas (n = 10, 59%) had a disrupted E2 gene. Three of the oropharyngeal
      tumors and two of the non-oropharyngeal tumors had deletions within E2. Detection
      of an intact E2 gene was associated with a higher DNA viral load and increased
      E2/E6/E7, ARF and INK4A expression in oropharyngeal tumors. Oropharyngeal
      carcinomas with an intact E2 had a lower risk of loco-regional recurrence (log
      rank p = 0.04) and improved disease-specific survival (p = 0.03) compared to
      tumors with disrupted E2. In addition, high E7 expression was associated with
      lower risk of loco-regional recurrence (p = 0.004) as was high E6 expression (p =
      0.006). In summary, an intact E2 gene is more common in HPV16 positive
      oropharyngeal than non-oropharyngeal carcinomas; the presence of an intact E2
      gene is associated with higher HPV viral load, higher viral oncogene expression,
      and improved clinical outcome compared to patients with a disrupted E2 gene in
      oropharyngeal cancer.

PMID- 29451893
TI  - Vegetative compatibility groups partition variation in the virulence of
      Verticillium dahliae on strawberry.
AB  - Verticillium dahliae infection of strawberry (Fragaria x ananassa) is a major
      cause of disease-induced wilting in soil-grown strawberries across the world. To
      understand what components of the pathogen are affecting disease expression, the
      presence of the known effector VdAve1 was screened in a sample of Verticillium
      dahliae isolates. Isolates from strawberry were found to contain VdAve1 and were
      divided into two major clades, based upon their vegetative compatibility groups
      (VCG); no UK strawberry isolates contained VdAve1. VC clade was strongly related
      to their virulence levels. VdAve1-containing isolates pathogenic on strawberry
      were found in both clades, in contrast to some recently published findings. On
      strawberry, VdAve1-containing isolates had significantly higher virulence during
      early infection, which diminished in significance as the infection progressed.
      Transformation of a virulent non-VdAve1 containing isolate, with VdAve1 was found
      neither to increase nor decrease virulence when inoculated on a susceptible
      strawberry cultivar. There are therefore virulence factors that are epistatic to
      VdAve1 and potentially multiple independent routes to high virulence on
      strawberry in V. dahliae lineages. Genome sequencing a subset of isolates across
      the two VCGs revealed that isolates were differentiated at the whole genome level
      and contained multiple changes in putative effector content, indicating that
      different clonal VCGs may have evolved different strategies for infecting
      strawberry, leading to different virulence levels in pathogenicity tests. It is
      therefore important to consider both clonal lineage and effector complement as
      the adaptive potential of each lineage will differ, even if they contain the same
      race determining effector.

PMID- 29451894
TI  - Trade-off between synergy and efficacy in combinations of HIV-1 latency-reversing
      agents.
AB  - Eradicating HIV-1 infection is difficult because of the reservoir of latently
      infected cells that gets established soon after infection, remains hidden from
      antiretroviral drugs and host immune responses, and retains the capacity to
      reignite infection following the cessation of treatment. Drugs called latency
      reversing agents (LRAs) are being developed to reactivate latently infected cells
      and render them susceptible to viral cytopathicity or immune killing. Whereas
      individual LRAs have failed to induce adequate reactivation, pairs of LRAs have
      been identified recently that act synergistically and hugely increase
      reactivation levels compared to individual LRAs. The maximum synergy achievable
      with LRA pairs is of clinical importance, as it would allow latency-reversal with
      minimal drug exposure. Here, we employed stochastic simulations of HIV-1
      transcription and translation in latently infected cells to estimate this maximum
      synergy. We incorporated the predominant mechanisms of action of the two most
      promising classes of LRAs, namely, protein kinase C agonists and histone
      deacetylase inhibitors, and quantified the activity of individual LRAs in the two
      classes by mapping our simulations to corresponding in vitro experiments. Without
      any adjustable parameters, our simulations then quantitatively captured
      experimental observations of latency-reversal when the LRAs were used in pairs.
      Performing simulations representing a wide range of drug concentrations, we
      estimated the maximum synergy achievable with these LRA pairs. Importantly, we
      found with all the LRA pairs we considered that concentrations yielding the
      maximum synergy did not yield the maximum latency-reversal. Increasing
      concentrations to increase latency-reversal compromised synergy, unravelling a
      trade-off between synergy and efficacy in LRA combinations. The maximum synergy
      realizable with LRA pairs would thus be restricted by the desired level of
      latency-reversal, a constrained optimum we elucidated with our simulations. We
      expect this trade-off to be important in defining optimal LRA combinations that
      would maximize synergy while ensuring adequate latency-reversal.

PMID- 29451895
TI  - Metabolic enzyme cost explains variable trade-offs between microbial growth rate
      and yield.
AB  - Microbes may maximize the number of daughter cells per time or per amount of
      nutrients consumed. These two strategies correspond, respectively, to the use of
      enzyme-efficient or substrate-efficient metabolic pathways. In reality, fast
      growth is often associated with wasteful, yield-inefficient metabolism, and a
      general thermodynamic trade-off between growth rate and biomass yield has been
      proposed to explain this. We studied growth rate/yield trade-offs by using a
      novel modeling framework, Enzyme-Flux Cost Minimization (EFCM) and by assuming
      that the growth rate depends directly on the enzyme investment per rate of
      biomass production. In a comprehensive mathematical model of core metabolism in
      E. coli, we screened all elementary flux modes leading to cell synthesis,
      characterized them by the growth rates and yields they provide, and studied the
      shape of the resulting rate/yield Pareto front. By varying the model parameters,
      we found that the rate/yield trade-off is not universal, but depends on metabolic
      kinetics and environmental conditions. A prominent trade-off emerges under oxygen
      limited growth, where yield-inefficient pathways support a 2-to-3 times higher
      growth rate than yield-efficient pathways. EFCM can be widely used to predict
      optimal metabolic states and growth rates under varying nutrient levels,
      perturbations of enzyme parameters, and single or multiple gene knockouts.

PMID- 29451897
TI  - Selective identification of somatic mutations in pancreatic cancer cells through
      a combination of next-generation sequencing of plasma DNA using molecular
      barcodes and a bioinformatic variant filter.
AB  - The accuracy of next-generation sequencing (NGS) for detecting tumor-specific
      mutations in plasma DNA is hindered by errors introduced during PCR/sequencing,
      base substitutions caused by DNA damage, and pre-existing mutations in normal
      cells that are present at a low frequency. Here, we performed NGS of genes
      related to pancreatic cancer (comprising 2.8 kb of genomic DNA) in plasma DNA
      (average 4.5 ng) using molecular barcodes. The average number of sequenced
      molecules was 900, and the sequencing depth per molecule was 100 or more. We also
      developed a bioinformatic variant filter, called CV78, to remove variants that
      were not considered to be tumor-specific, i.e., those that are either absent or
      occur at low frequencies in the Catalogue of Somatic Mutations in Cancer
      database. In a cohort comprising 57 pancreatic cancer patients and 12 healthy
      individuals, sequencing initially identified variants in 31 (54%) and 5 (42%),
      respectively, whereas after applying the CV78 filter, 19 (33%) and zero were
      variant-positive. In a validation cohort consisting of 86 patients with
      pancreatic cancer and 20 patients with intraductal papillary mucinous neoplasm
      (IPMN), 62 (72%) with pancreatic cancer patients and 10 (50%) IPMN patients were
      initially variant positive. After CV78 filtering, these values were reduced to 32
      (37%) and 1 (5%), respectively. The variant allele frequency of filtered variants
      in plasma ranged from 0.25% to 76.1%. Therefore, combining NGS and molecular
      barcodes with subsequent filtering is likely to eliminate most non-tumor-specific
      mutations.

PMID- 29451896
TI  - Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119
      patients.
AB  - OBJECTIVE: Hypomyelinating disorders are a group of clinically and genetically
      heterogeneous diseases characterized by neurological deterioration with
      hypomyelination visible on brain MRI scans. This study was aimed to clarify the
      clinical and genetic features of HMDs in Chinese population. METHODS: 119
      patients with hypomyelinating disorders in Chinese population were enrolled and
      evaluated based on their history, clinical manifestation, laboratory
      examinations, series of brain MRI with follow-up, genetic etiological tests
      including chromosomal analysis, multiplex ligation probe amplification, Sanger
      sequencing, targeted enrichment-based next-generation sequencing and whole exome
      sequencing. RESULTS: Clinical and genetic features of hypomyelinating disorders
      were revealed. Nine different hypomyelinating disorders were identified in 119
      patients: Pelizaeus-Merzbacher disease (94, 79%), Pelizaeus-Merzbacher-like
      disease (10, 8%), hypomyelination with atrophy of the basal ganglia and
      cerebellum (3, 3%), GM1 gangliosidosis (5, 4%), GM2 gangliosidosis (3, 3%),
      trichothiodystrophy (1, 1%), Pol III-related leukodystrophy (1, 1%),
      hypomyelinating leukodystrophy type 9 (1, 1%), and chromosome 18q deletion
      syndrome (1, 1%). Of the sample, 94% (112/119) of the patients were genetically
      diagnosed, including 111 with mutations distributing across 9 genes including
      PLP1, GJC2, TUBB4A, GLB1, HEXA, HEXB, ERCC2, POLR3A, and RARS and 1 with mosaic
      chromosomal change of 46, XX,del(18)(q21.3)/46,XX,r(18)(p11.32q21.3)/45,XX,-18.
      Eighteen novel mutations were discovered. Mutations in POLR3A and RARS were first
      identified in Chinese patients with Pol III-related leukodystrophy and
      hypomyelinating leukodystrophy, respectively. SIGNIFICANCE: This is the first
      report on clinical and genetic features of hypomyelinating disorders with a large
      sample of patients in Chinese population, identifying 18 novel mutations
      especially mutations in POLR3A and RARS in Chinese patients, expanding clinical
      and genetic spectrums of hypomyelinating disorders.

PMID- 29451898
TI  - Integrating linear optimization with structural modeling to increase HIV
      neutralization breadth.
AB  - Computational protein design has been successful in modeling fixed backbone
      proteins in a single conformation. However, when modeling large ensembles of
      flexible proteins, current methods in protein design have been insufficient.
      Large barriers in the energy landscape are difficult to traverse while
      redesigning a protein sequence, and as a result current design methods only
      sample a fraction of available sequence space. We propose a new computational
      approach that combines traditional structure-based modeling using the Rosetta
      software suite with machine learning and integer linear programming to overcome
      limitations in the Rosetta sampling methods. We demonstrate the effectiveness of
      this method, which we call BROAD, by benchmarking the performance on increasing
      predicted breadth of anti-HIV antibodies. We use this novel method to increase
      predicted breadth of naturally-occurring antibody VRC23 against a panel of 180
      divergent HIV viral strains and achieve 100% predicted binding against the panel.
      In addition, we compare the performance of this method to state-of-the-art
      multistate design in Rosetta and show that we can outperform the existing method
      significantly. We further demonstrate that sequences recovered by this method
      recover known binding motifs of broadly neutralizing anti-HIV antibodies.
      Finally, our approach is general and can be extended easily to other protein
      systems. Although our modeled antibodies were not tested in vitro, we predict
      that these variants would have greatly increased breadth compared to the wild
      type antibody.

PMID- 29451899
TI  - Cooperation enhanced by the coevolution of teaching activity in evolutionary
      prisoner's dilemma games with voluntary participation.
AB  - Voluntary participation, as an additional strategy involved in repeated games,
      has been proved to be an efficient way to promote the evolution of cooperation
      theoretically and empirically. Besides, current studies show that the coevolution
      of teaching activity can promote cooperation. Thus, inspired by aforementioned
      above, we investigate the effect of coevolution of teaching activity on the
      evolution of cooperation for prisoner's dilemma game with voluntary
      participation: when the focal player successfully enforces its strategy on the
      opponent, his teaching ability will get an increase. Through numerical
      simulation, we have shown that voluntary participation could effectively promote
      the fraction of cooperation, which is also affected by the value of increment.
      Furthermore, we investigate the influence of the increment value on the density
      of different strategies and find that there exists an optimal increment value
      that plays an utmost role on the evolutionary dynamics. With regard to this
      observation, we unveil that an optimal value of increment can lead to strongest
      heterogeneity in agents' teaching ability, further promoting the evolution of
      cooperation.

PMID- 29451900
TI  - The ARID1A, p53 and beta-Catenin statuses are strong prognosticators in clear
      cell and endometrioid carcinoma of the ovary and the endometrium.
AB  - AIM: The objective of this study was to evaluate the prognostic value of ARID1A,
      p53, p21, p16 and beta-Catenin in endometrioid and clear cell ovarian and
      endometrial carcinomas. MATERIALS AND METHODS: 97 tumors were available for
      analysis of ARID1A, p53, p21, p16 and beta-Catenin with the techniques of tissue
      microarray and immunohistochemistry. 32 were ovarian carcinomas and 65 were
      endometrial carcinomas. RESULTS: Endometrioid ovarian carcinomas showed negative
      staining for ARID1A (a) and p21 (b), aberrant expression of p53 (c) and p16 (d)
      and beta-Catenin positive nuclear expression (e) respectively in 19% (a), 100%
      (b), 28.6% (c), 52.4% (d) and 4.8% (e) of all cases. In the group of clear cell
      ovarian carcinomas it was 63.6% (a), 100% (b), 81.8% (c), 54.5% (d) and 0% (e).
      For endometrioid uterine carcinomas it was 75.7% (a), 94.9% (b), 30.5% (c), 52.1%
      (d) and 6.8% (e) and for clear cell uterine carcinomas it was 8.6% (a), 100% (b),
      50% (c), 100% (d) and 0% (e). Survival analysis showed that negative expression
      of ARID1A, p53 aberrant expression and beta-Catenin nuclear positive staining are
      independent negative prognosticators in both, clear cell and endometrioid
      carcinoma, regardless of ovarian or uterine origin. Cox-Regression analysis
      showed them again as negative prognostic factors. Furthermore, we found a
      significant correlation between ARID1A and beta-Catenin expression in
      endometrioid uterine tumors. CONCLUSION: The analyzed gynaecological carcinoma
      showed a distinct expression scheme of proteins that are associated with tumor
      suppression. We may conclude that ARID1A, p53 and beta-Catenin are the strongest
      prognostic factors by analyzing a subgroup of tumor suppressor genes in clear
      cell and endometrioid subtypes of ovarian and endometrial cancer and may be used
      along with traditional morphological and clinical characteristics for prognosis.

PMID- 29451901
TI  - The novel antibiotic rhodomyrtone traps membrane proteins in vesicles with
      increased fluidity.
AB  - The acylphloroglucinol rhodomyrtone is a promising new antibiotic isolated from
      the rose myrtle Rhodomyrtus tomentosa, a plant used in Asian traditional
      medicine. While many studies have demonstrated its antibacterial potential in a
      variety of clinical applications, very little is known about the mechanism of
      action of rhodomyrtone. Preceding studies have been focused on intracellular
      targets, but no specific intracellular protein could be confirmed as main target.
      Using live cell, high-resolution, and electron microscopy we demonstrate that
      rhodomyrtone causes large membrane invaginations with a dramatic increase in
      fluidity, which attract a broad range of membrane proteins. Invaginations then
      form intracellular vesicles, thereby trapping these proteins. Aberrant protein
      localization impairs several cellular functions, including the respiratory chain
      and the ATP synthase complex. Being uncharged and devoid of a particular
      amphipathic structure, rhodomyrtone did not seem to be a typical membrane
      inserting molecule. In fact, molecular dynamics simulations showed that instead
      of inserting into the bilayer, rhodomyrtone transiently binds to phospholipid
      head groups and causes distortion of lipid packing, providing explanations for
      membrane fluidization and induction of membrane curvature. Both its transient
      binding mode and its ability to form protein-trapping membrane vesicles are
      unique, making it an attractive new antibiotic candidate with a novel mechanism
      of action.

PMID- 29451902
TI  - An artificial miRNA system reveals that relative contribution of translational
      inhibition to miRNA-mediated regulation depends on environmental and
      developmental factors in Arabidopsis thaliana.
AB  - Development and fitness of any organism rely on properly controlled gene
      expression. This is especially true for plants, as their development is
      determined by both internal and external cues. MicroRNAs (miRNAs) are embedded in
      the genetic cascades that integrate and translate those cues into developmental
      programs. miRNAs negatively regulate their target genes mainly post
      transcriptionally through two co-existing mechanisms; mRNA cleavage and
      translational inhibition. Despite our increasing knowledge about the genetic and
      biochemical processes involved in those concurrent mechanisms, little is known
      about their relative contributions to the overall miRNA-mediated regulation. Here
      we show that co-existence of cleavage and translational inhibition is dependent
      on growth temperature and developmental stage. We found that efficiency of an
      artificial miRNA-mediated (amiRNA) gene silencing declines with age during
      vegetative development in a temperature-dependent manner. That decline is mainly
      due to a reduction on the contribution from translational inhibition. Both,
      temperature and developmental stage were also found to affect mature amiRNA
      accumulation and the expression patterns of the core players involved in miRNA
      biogenesis and action. Therefore, that suggests that each miRNA family
      specifically regulates their respective targets, while temperature and growth
      might influence the performance of miRNA-dependent regulation in a more general
      way.

PMID- 29451903
TI  - Stability lies in flowers: Plant diversification mediating shifts in arthropod
      food webs.
AB  - Arthropod community composition in agricultural landscapes is dependent on
      habitat characteristics, such as plant composition, landscape homogeneity and the
      presence of key resources, which are usually absent in monocultures. Manipulating
      agroecosystems through the insertion of in-field floral resources is a useful
      technique to reduce the deleterious effects of habitat simplification. Food web
      analysis can clarify how the community reacts to the presence of floral resources
      which favour ecosystem services such as biological control of pest species. Here,
      we reported quantitative and qualitative alterations in arthropod food web
      complexity due to the presence of floral resources from the Mexican marigold
      (Tagetes erecta L.) in a field scale lettuce community network. The presence of
      marigold flowers in the field successfully increased richness, body size, and the
      numerical and biomass abundance of natural enemies in the lettuce arthropod
      community, which affected the number of links, vulnerability, generality,
      omnivory rate and food chain length in the community, which are key factors for
      the stability of relationships between species. Our results reinforce the notion
      that diversification through insertion of floral resources may assist in
      preventing pest outbreaks in agroecosystems. This community approach to arthropod
      interactions in agricultural landscapes can be used in the future to predict the
      effect of different management practices in the food web to contribute with a
      more sustainable management of arthropod pest species.

PMID- 29451904
TI  - Phytoforensics: Trees as bioindicators of potential indoor exposure via vapor
      intrusion.
AB  - Human exposure to volatile organic compounds (VOCs) via vapor intrusion (VI) is
      an emerging public health concern with notable detrimental impacts on public
      health. Phytoforensics, plant sampling to semi-quantitatively delineate
      subsurface contamination, provides a potential non-invasive screening approach to
      detect VI potential, and plant sampling is effective and also time- and cost
      efficient. Existing VI assessment methods are time- and resource-intensive,
      invasive, and require access into residential and commercial buildings to drill
      holes through basement slabs to install sampling ports or require substantial
      equipment to install groundwater or soil vapor sampling outside the home. Tree
      core samples collected in 2 days at the PCE Southeast Contamination Site in York,
      Nebraska were analyzed for tetrachloroethene (PCE) and results demonstrated
      positive correlations with groundwater, soil, soil-gas, sub-slab, and indoor-air
      samples collected over a 2-year period. Because tree-core samples were not
      collocated with other samples, interpolated surfaces of PCE concentrations were
      estimated so that comparisons could be made between pairs of data. Results
      indicate moderate to high correlation with average indoor-air and sub-slab PCE
      concentrations over long periods of time (months to years) to an interpolated
      tree-core PCE concentration surface, with Spearman's correlation coefficients
      (rho) ranging from 0.31 to 0.53 that are comparable to the pairwise correlation
      between sub-slab and indoor-air PCE concentrations (rho = 0.55, n = 89). Strong
      correlations between soil-gas, sub-slab, and indoor-air PCE concentrations and an
      interpolated tree-core PCE concentration surface indicate that trees are valid
      indicators of potential VI and human exposure to subsurface environment
      pollutants. The rapid and non-invasive nature of tree sampling are notable
      advantages: even with less than 60 trees in the vicinity of the source area,
      roughly 12 hours of tree-core sampling with minimal equipment at the PCE
      Southeast Contamination Site was sufficient to delineate vapor intrusion
      potential in the study area and offered comparable delineation to traditional sub
      slab sampling performed at 140 properties over a period of approximately 2 years.

PMID- 29451905
TI  - Otoacoustic emissions from ears with spontaneous activity behave differently to
      those without: Stronger responses to tone bursts as well as to clicks.
AB  - It has been reported that both click-evoked otoacoustic emissions (CEOAEs) and
      distortion product otoacoustic emissions (DPOAEs) have higher amplitudes in ears
      that possess spontaneous otoacoustic emissions (SOAEs). The general aim of the
      present study was to investigate whether the presence of spontaneous activity in
      the cochlea affected tone-burst evoked otoacoustic emissions (TBOAEs). As a
      benchmark, the study also measured growth functions of CEOAEs. Spontaneous
      activity in the cochlea was measured by the level of synchronized spontaneous
      otoacoustic emissions (SSOAEs), an emission evoked by a click but closely related
      to spontaneous otoacoustic emissions (SOAEs, which are detectable without any
      stimulus). Measurements were made on a group of 15 adults whose ears were
      categorized as either having recordable SSOAEs or no SSOAEs. In each ear, CEOAEs
      and TBOAEs were registered at frequencies of 0.5, 1, 2, and 4 kHz, and
      input/output functions were measured at 40, 50, 60, 70, and 80 dB SPL. Global and
      half-octave-band values of response level and latency were estimated. Our main
      finding was that in ears with spontaneous activity, TBOAEs had higher levels than
      in ears without. The difference was more apparent for global values, but were
      also seen with half-octave-band analysis. Input/output functions had similar
      growth rates for ears with and without SSOAEs. There were no significant
      differences in latencies between TBOAEs from ears with and without SSOAEs,
      although latencies tended to be longer for lower stimulus levels and lower
      stimulus frequencies. When TBOAE levels were compared to CEOAE levels, the latter
      showed greater differences between recordings from ears with and without SSOAEs.
      Although TBOAEs reflect activity from a more restricted cochlear region than
      CEOAEs, at all stimulus frequencies their behavior still depends on whether
      SSOAEs are present or not.

PMID- 29451907
TI  - Timber isoscapes. A case study in a mountain area in the Italian Alps.
AB  - BACKGROUND: Local timber is still one of the main sources of work and income for
      mountain communities. However, illegal logging is a major cause of deforestation
      in many countries and has significant impacts on local communities and
      biodiversity. Techniques for tracing timber would provide a useful tool to
      protect local timber industries and contribute to the fight against illegal
      logging. Although considerable progress has been made in food traceability,
      timber provenance is still a somewhat neglected research area. Stable isotope
      ratios in plants are known to reflect geographical variations. This study reports
      accurate spatial distribution of delta18O and delta2H in timber from north
      eastern Italy (Trentino) in order to trace geographical origin. METHODOLOGY AND
      PRINCIPAL FINDINGS: We tested the accuracy of four kriging methods using an
      annual resolution of delta18O and delta2H measured in Picea abies. Pearson's
      correlation coefficients revealed altitude to be the most appropriate covariate
      for the cokriging model, which has ultimately proved to be the best method due to
      its low estimation error. CONCLUSIONS: We present regional maps of interpolated
      delta18O and delta2H in Picea abies wood together with the 95% confidence
      intervals. The strong spatial structure of the data demonstrates the potential of
      multivariate spatial interpolation, even in a highly heterogeneous area such as
      the Alps. We believe that this geospatial approach can be successfully applied on
      a wider scale in order to combat illegal logging.

PMID- 29451906
TI  - Brain changes due to hypoxia during light anaesthesia can be prevented by
      deepening anaesthesia; a study in rats.
AB  - In anaesthetic practice the risk of cerebral ischemic/hypoxic damage is thought
      to be attenuated by deep anaesthesia. The rationale is that deeper anaesthesia
      reduces cerebral oxygen demand more than light anaesthesia, thereby increasing
      the tolerance to ischemia or hypoxia. However, evidence to support this is
      scarce. We thus investigated the influence of light versus deep anaesthesia on
      the responses of rat brains to a period of hypoxia. In the first experiment we
      exposed adult male Wistar rats to deep or light propofol anaesthesia and then
      performed [18F]- Fludeoxyglucose (FDG) Positron Emission Tomography (PET) scans
      to verify the extent of cerebral metabolic suppression. In subsequent
      experiments, rats were subjected to light/deep propofol anaesthesia and then
      exposed to a period of hypoxia or ongoing normoxia (n = 9-11 per group). A
      further 5 rats, not exposed to anaesthesia or hypoxia, served as controls. Four
      days later a Novel Object Recognition (NOR) test was performed to assess mood and
      cognition. After another 4 days, the animals were sacrificed for later
      immunohistochemical analyses of neurogenesis/neuroplasticity (Doublecortin; DCX),
      Brain Derived Neurotrophic Factor (BDNF) expression and neuroinflammation
      (Ionized calcium-binding adaptor protein-1; Iba-1) in hippocampal and piriform
      cortex slices. The hippocampi of rats subjected to hypoxia during light
      anaesthesia showed lower DCX positivity, and therefore lower neurogenesis, but
      higher BDNF levels and microglia hyper-ramification. Exploration was reduced, but
      no significant effect on NOR was observed. In the piriform cortex, higher DCX
      positivity was observed, associated with neuroplasticity. All these effects were
      attenuated by deep anaesthesia. Deepening anaesthesia attenuated the brain
      changes associated with hypoxia. Hypoxia during light anaesthesia had a prolonged
      effect on the brain, but no impairment in cognitive function was observed.
      Although reduced hippocampal neurogenesis may be considered unfavourable, higher
      BDNF expression, associated with microglia hyper-ramification may suggest
      activation of repair mechanisms. Increased neuroplasticity observed in the
      piriform cortex supports this, and might reflect a prolonged state of alertness
      rather than damage.

PMID- 29451908
TI  - Cas9-mediated excision of proximal DNaseI/H3K4me3 signatures confers robust
      silencing of microRNA and long non-coding RNA genes.
AB  - CRISPR/Cas9-based approaches have greatly facilitated targeted genomic deletions.
      Contrary to coding genes however, which can be functionally knocked out by frame
      shift mutagenesis, non-coding RNA (ncRNA) gene knockouts have remained
      challenging. Here we present a universal ncRNA knockout approach guided by
      epigenetic hallmarks, which enables robust gene silencing even in provisionally
      annotated gene loci. We build on previous work reporting the presence of
      overlapping histone H3 lysine 4 tri-methylation (H3K4me3) and DNaseI
      hypersensitivity sites around the transcriptional start sites of most genes. We
      demonstrate that excision of this gene-proximal signature leads to loss of
      microRNA and lincRNA transcription and reveals ncRNA phenotypes. Exemplarily we
      demonstrate silencing of the constitutively transcribed MALAT1 lincRNA gene as
      well as of the inducible miR-146a and miR-155 genes in human monocytes. Our
      results validate a role of miR-146a and miR-155 in negative feedback control of
      the activity of inflammation master-regulator NFkappaB and suggest that cell
      cycle control is a unique feature of miR-155. We suggest that our epigenetically
      guided CRISPR approach may improve existing ncRNA knockout strategies and
      contribute to the development of high-confidence ncRNA phenotyping applications.

PMID- 29451909
TI  - Rapid purification of giant lipid vesicles by microfiltration.
AB  - Giant lipid vesicles (GVs) are emerging models for investigating the properties
      and reactivity of cell-like microcompartments, providing useful information about
      plausible protocellular structures in primitive times, as well as for the modern
      synthetic biology goal of constructing the first artificial cell from its
      reconstituted and partly modified components. Here we explore a novel methodology
      of GV purification by microfiltration under reduced pressure, operated by a
      simple apparatus. The method has been characterized in terms of flow rate, amount
      of lipid loss, quality of recovered GVs, and size distribution. A case study is
      reported to show the practicability of GV microfiltration. A clickable
      fluorescent probe was encapsulated inside GVs; more than 99.9% of the non
      entrapped probe was easily and rapidly removed by multiple microfiltrations. This
      novel methodology is briefly discussed as a future tool for selection experiments
      on GV populations.

PMID- 29451910
TI  - The fruit and vegetable import pathway for potential invasive pest arrivals.
AB  - The expansion of international trade in commodities increases the risk of alien
      species invasions. Invaders are difficult to detect on introduction, so
      prevention remains the preferred strategy for managing the threat of invasions.
      Propagule pressure has been shown to be a good predictor of invasion risk. Most
      studies to date, however, link potential invasive species arrivals with indirect
      measures of propagule pressure such as aggregate trade volumes. This paper
      estimates propagule pressure using data that measure actual arrivals.
      Specifically, it uses inspection data that covers almost all U.S. fruit and
      vegetable imports from 2005-2014 to estimate a logit model of the probability of
      potential invasive species arrival and expected propagule frequencies for 2,240
      commodity/country of origin combinations. Clear patterns in the geographic origin
      and commodity pathways for potential pests are identified. The average
      probability of arrival is low, approximately 0.03, but is two to ten times higher
      for some commodities, most notably herbs. We identify commodities with a high
      number of expected arrivals due to either a large volume of trade, high
      interception rates, or a combination of both. Seven of the top ten countries of
      origin for propagule frequency are from the Western Hemisphere and further trade
      liberalization within the Western Hemisphere is likely to heighten challenges to
      enforcement of US phytosanitary standards. Patterns in the data can help identify
      the commodities and countries of origin in greatest need of technical assistance
      and guide targeting of surveillance for the pathways of greatest phytosanitary
      concern.

PMID- 29451911
TI  - Carbon stock of Moso bamboo (Phyllostachys pubescens) forests along a latitude
      gradient in the subtropical region of China.
AB  - Latitude is an important factor that influences the carbon stock of Moso bamboo
      (Phyllostachys pubescens) forests. Accurate estimation of the carbon stock of
      Moso bamboo forest can contribute to sufficient evaluation of forests in carbon
      sequestration worldwide. Nevertheless, the effect of latitude on the carbon stock
      of Moso bamboo remains unclear. In this study, a field survey with 36 plots of
      Moso bamboo forests along a latitude gradient was conducted to investigate carbon
      stock. Results showed that the diameter at breast height (DBH) of Moso bamboo
      culms increased from 8.37 cm to 10.12 cm that well fitted by Weibull model,
      whereas the bamboo culm density decreased from 4722 culm ha-1 to 3400 culm ha-1
      with increasing latitude. The bamboo biomass carbon decreased from 60.58 Mg C ha
      1 to 48.31 Mg C ha-1 from north to south. The total carbon stock of Moso bamboo
      forests, which comprises soil and biomass carbon, ranged from 87.83 Mg C ha-1 to
      119.5 Mg C ha-1 and linearly increased with latitude. As a fast-growing plant,
      Moso bamboo could be harvested amounts of 6.0 Mg C ha-1 to 7.6 Mg C ha-1
      annually, which indicates a high potential of this species for carbon
      sequestration. Parameters obtained in this study can be used to accurately
      estimate the carbon stock of Moso bamboo forest to establish models of the global
      carbon balance.

PMID- 29451912
TI  - Expression of cell cycle regulators and frequency of TP53 mutations in high risk
      gastrointestinal stromal tumors prior to adjuvant imatinib treatment.
AB  - Despite of multitude investigations no reliable prognostic immunohistochemical
      biomarkers in GIST have been established so far with added value to predict the
      recurrence risk of high risk GIST besides mitotic count, primary location and
      size. In this study, we analyzed the prognostic relevance of eight cell cycle and
      apoptosis modulators and of TP53 mutations for prognosis in GIST with high risk
      of recurrence prior to adjuvant treatment with imatinib. In total, 400 patients
      with high risk for GIST recurrence were randomly assigned for adjuvant imatinib
      either for one or for three years following laparotomy. 320 primary tumor samples
      with available tumor tissue were immunohistochemically analyzed prior to
      treatment for the expression of cell cycle regulators and apoptosis modulators
      cyclin D1, p21, p16, CDK4, E2F1, MDM2, p53 and p-RB1. TP53 mutational analysis
      was possible in 245 cases. A high expression of CDK4 was observed in 32.8% of all
      cases and was associated with a favorable recurrence free survival (RFS), whereas
      high expression of MDM2 (12.2%) or p53 (35.3%) was associated with a shorter RFS.
      These results were independent from the primary KIT or PDGFRA mutation. In GISTs
      with higher mitotic counts was a significantly increased expression of cyclin D1,
      p53 and E2F1. The expression of p16 and E2F1 significantly correlated to a non
      gastric localization. Furthermore, we observed a significant higher expression of
      p21 and E2F1 in KIT mutant GISTs compared to PDGFRA mutant and wt GISTs. The
      overall frequency of TP53 mutations was low (n = 8; 3.5%) and could not be
      predicted by the immunohistochemical expression of p53. In summary, mutation
      analysis in TP53 plays a minor role in the subgroup of high-risk GIST before
      adjuvant treatment with imatinib. Strong expression of MDM2 and p53 correlated
      with a shorter recurrence free survival, whereas a strong expression of CDK4
      correlated to a better recurrence free survival.

PMID- 29451914
TI  - Correction: Effects of Low Dose Metformin on Metabolic Traits in Clozapine
      Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double
      Blind, Placebo-Controlled Study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0168347.].

PMID- 29451913
TI  - Identification of the S-transferase like superfamily bacillithiol transferases
      encoded by Bacillus subtilis.
AB  - Bacillithiol is a low molecular weight thiol found in Firmicutes that is
      analogous to glutathione, which is absent in these bacteria. Bacillithiol
      transferases catalyze the transfer of bacillithiol to various substrates. The S
      transferase-like (STL) superfamily contains over 30,000 putative members,
      including bacillithiol transferases. Proteins in this family are extremely
      divergent and are related by structural rather than sequence similarity, leaving
      it unclear if all share the same biochemical activity. Bacillus subtilis encodes
      eight predicted STL superfamily members, only one of which has been shown to be a
      bacillithiol transferase. Here we find that the seven remaining proteins show
      varying levels of metal dependent bacillithiol transferase activity. We have
      renamed the eight enzymes BstA-H. Mass spectrometry and gene expression studies
      revealed that all of the enzymes are produced to varying levels during growth and
      sporulation, with BstB and BstE being the most abundant and BstF and BstH being
      the least abundant. Interestingly, several bacillithiol transferases are induced
      in the mother cell during sporulation. A strain lacking all eight bacillithiol
      transferases showed normal growth in the presence of stressors that adversely
      affect growth of bacillithiol-deficient strains, such as paraquat and CdCl2.
      Thus, the STL bacillithiol transferases represent a new group of proteins that
      play currently unknown, but potentially significant roles in bacillithiol
      dependent reactions. We conclude that these enzymes are highly divergent, perhaps
      to cope with an equally diverse array of endogenous or exogenous toxic
      metabolites and oxidants.

PMID- 29451915
TI  - Synchronic historical patterns of species diversification in seasonal
      aplocheiloid killifishes of the semi-arid Brazilian Caatinga.
AB  - The Caatinga is the largest nucleus of seasonally dry tropical forests in South
      America, but little is known about the evolutionary history and biogeography of
      endemic organisms. Evolutionary diversification and distribution of terrestrial
      vertebrates endemic to the Caatinga have been explained by palaeogeographical
      Neogene episodes, mostly related to changes in the course of the Sao Francisco
      River, the largest river in the region. Our objective is to estimate the timing
      of divergence of two endemic groups of short-lived seasonal killifishes
      inhabiting all ecoregions of the Caatinga, testing the occurrence of synchronic
      events of spatial diversification in light of available data on regional
      palaeogeography. We performed independent time-calibrated phylogenetic molecular
      analyses for two clades of sympatric and geographically widespread seasonal
      killifishes endemic to the Caatinga, the Hypsolebias antenori group and the
      Cynolebias alpha-clade. Our results consistently indicate that species
      diversification took place synchronically in both groups, as well as it is
      contemporary to diversification of other organisms adapted to life in the semi
      arid Caatinga, including lizards and small mammals. Both groups originated during
      the Miocene, but species diversification started between the Late Miocene and
      Early Pliocene, when global cooling probably favoured the expansion of semi-arid
      areas. Synchronic diversification patterns found are chronologically related to
      Tertiary palaeogeographical reorganizations associated to continental drift and
      to Quaternary climatic changes, corroborating the recent proposal that South
      American biodiversity has been continuously shaped between the Late Paleogene and
      Pleistocene.

PMID- 29451916
TI  - Awareness and attitude of the public toward personalized medicine in Korea.
AB  - OBJECTIVES: As personalized medicine (PM) is expected to greatly improve health
      outcomes, efforts have recently been made for its clinical implementation in
      Korea. We aimed to evaluate public awareness and attitude regarding PM. METHODS:
      We performed a self-administered questionnaire survey to 703 adults, who
      participated in the survey on a voluntary basis. The primary outcome measures
      included public knowledge, attitude, and acceptance of PM. We conducted
      multinomial multivariate logistic analysis for outcome variables with three
      response categories and performed multivariate logistic regression analyses for
      dichotomous outcome variables. RESULTS: Only 28% of participants had knowledge
      that genetic factors can contribute to inter-individual variations in drug
      response and the definition of PM (199 out of 702). Higher family income was
      correlated with greater knowledge concerning PM (OR = 3.76, p = 0.034). A
      majority of respondents preferred integrated pharmacogenomic testing over drug
      specific testing and agreed to inclusion of pharmacogenomic testing in the
      national health examination (64% and 77%, respectively), but only 51% were
      willing to pay for it. DISCUSSION: Our results identify the urgent need for
      public education as well as the potential health disparities in access to PM.
      This study helps to frame policies for implementing PM in clinical practice.

PMID- 29451917
TI  - Perceived behavioral control as a potential precursor of walking three times a
      week: Patient's perspectives.
AB  - BACKGROUND: Behavior change theories can identify people's main motivations to
      engage in recommended health practices and thus provide better tools to design
      interventions, particularly human centered design interventions. OBJECTIVES: This
      study had two objectives: (a) to identify salient beliefs about walking three
      times a week for 30 minutes nonstop among patients with hypertension in a low
      resource setting and, (b) to measure the relationships among intentions,
      attitudes, perceived social pressure and perceived behavioral control about this
      behavior. METHODS: Face-to-face interviews with 34 people living with
      hypertension were conducted in September-October 2011 in Lima, Peru, and data
      analysis was performed in 2015. The Reasoned Action Approach was used to study
      the people's decisions to walk. We elicited people's salient beliefs and measured
      the theoretical constructs associated with this behavior. RESULTS: Results
      pointed at salient key behavioral, normative and control beliefs. In particular,
      perceived behavioral control appeared as an important determinant of walking and
      a small set of control beliefs were identified as potential targets of health
      communication campaigns, including (not) having someone to walk with, having work
      or responsibilities, or having no time. CONCLUSIONS: This theory-based study with
      a focus on end-users provides elements to inform the design of an intervention
      that would motivate people living with hypertension to walk on a regular basis in
      low-resource settings.

PMID- 29451919
TI  - Correction: Measuring 3D Hand and Finger Kinematics-A Comparison between Inertial
      Sensing and an Opto-Electronic Marker System.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0164889.].

PMID- 29451918
TI  - Manipulation of the rhizosphere microbial community through application of a new
      bio-organic fertilizer improves watermelon quality and health.
AB  - Bio-organic fertilizers (BOFs) combine functional microbes with a suitable
      substrate and have been shown to effectively suppress soil-borne diseases and
      promote plant growth. Here, we developed a novel bio-organic fertilizer (BOF) by
      fermentation of a cow plus chicken manure (M) compost using Fen-liquor Daqu (FLD)
      as a fermentation starter and compared the compositions of bacterial and fungal
      communities in the rhizosphere soil of watermelon plants after treatment with
      different fertilizers. Further, we aimed to explore the mechanisms underlying
      plant-promoting and disease (Fusarium wilt)-suppressing activities of each
      rhizosphere microbial community. The microbial communities of soil amended with
      cow plus chicken manure compost (S+M), soil amended with the BOF (S+BOF), and
      untreated control soil (S) without plants were analyzed through sequence analysis
      using the Illumina MiSeq platform. The results showed that a new microbial
      community was formed in the manure compost after fermentation by the Daqu.
      Application of the BOF to the soil induced remarkable changes in the rhizosphere
      microbial communities, with increased bacterial diversity and decreased fungal
      diversity. Most importantly, S+BOF showed the lowest abundance of Fusarium.
      Moreover, watermelon quality was higher (P < 0.05) in the S+BOF than in the S+M
      treatment. Thus, application of the BOF favorably altered the composition of the
      rhizosphere microbial community, suppressing Fusarium wilt disease and promoting
      plant quality.

PMID- 29451920
TI  - An upstream sequence modulates phenazine production at the level of transcription
      and translation in the biological control strain Pseudomonas chlororaphis 30-84.
AB  - Phenazines are bacterial secondary metabolites and play important roles in the
      antagonistic activity of the biological control strain P. chlororaphis 30-84
      against take-all disease of wheat. The expression of the P. chlororaphis 30-84
      phenazine biosynthetic operon (phzXYFABCD) is dependent on the PhzR/PhzI quorum
      sensing system located immediately upstream of the biosynthetic operon as well as
      other regulatory systems including Gac/Rsm. Bioinformatic analysis of the
      sequence between the divergently oriented phzR and phzX promoters identified
      features within the 5'-untranslated region (5'-UTR) of phzX that are conserved
      only among 2OHPCA producing Pseudomonas. The conserved sequence features are
      potentially capable of producing secondary structures that negatively modulate
      one or both promoters. Transcriptional and translational fusion assays revealed
      that deletion of 90-bp of sequence at the 5'-UTR of phzX led to up to 4-fold
      greater expression of the reporters with the deletion compared to the controls,
      which indicated this sequence negatively modulates phenazine gene expression both
      transcriptionally and translationally. This 90-bp sequence was deleted from the
      P. chlororaphis 30-84 chromosome, resulting in 30-84Enh, which produces
      significantly more phenazine than the wild-type while retaining quorum sensing
      control. The transcriptional expression of phzR/phzI and amount of AHL signal
      produced by 30-84Enh also were significantly greater than for the wild-type,
      suggesting this 90-bp sequence also negatively affects expression of the quorum
      sensing genes. In addition, deletion of the 90-bp partially relieved RsmE
      mediated translational repression, indicating a role for Gac/RsmE interaction.
      Compared to the wild-type, enhanced phenazine production by 30-84Enh resulted in
      improvement in fungal inhibition, biofilm formation, extracellular DNA release
      and suppression of take-all disease of wheat in soil without negative
      consequences on growth or rhizosphere persistence. This work provides greater
      insight into the regulation of phenazine biosynthesis with potential applications
      for improved biological control.

PMID- 29451921
TI  - The effectiveness of non-surgical intervention (Foot Orthoses) for paediatric
      flexible pes planus: A systematic review: Update.
AB  - BACKGROUND: Flexible pes planus (flat feet) in children is a common presenting
      condition in clinical practice due to concerns amongst parents and caregivers.
      While Foot Orthoses (FOs) are a popular intervention, their effectiveness remains
      unclear. Thus, the aim of this systematic review was to update the current
      evidence base for the effectiveness of FOs for paediatric flexible pes planus.
      METHODS: A systematic search of electronic databases (Cochrane, Medline, AMED,
      EMBASE, CINHAL, SportDiscus, Scopus and PEDro) was conducted from January 2011 to
      July 2017. Studies of children (0-18 years) diagnosed with flexible pes planus
      and intervention to be any type of Foot Orthoses (FOs) were included. This review
      was conducted and reported in line with the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) statement. McMaster critical review
      form for quantitative studies, was used to assess the methodological quality of
      the included studies. Given the heterogeneity of the included studies, a
      descriptive synthesis of the included studies was undertaken. RESULTS: Out of 606
      articles identified, 11 studies (three RCTs; two case-controls; five case-series
      and one single case study) met the inclusion criteria. A diverse range of pre
      fabricated and customised FOs were utilised and effectiveness measured through a
      plethora of outcomes. Summarised findings from the heterogeneous evidence base
      indicated that FOs may have a positive impact across a range of outcomes
      including pain, foot posture, gait, function and structural and kinetic measures.
      Despite these consistent positive outcomes reported in several studies, the
      current evidence base lacks clarity and uniformity in terms of diagnostic
      criteria, interventions delivered and outcomes measured for paediatric flexible
      pes planus. CONCLUSION: There continues to remain uncertainty on the
      effectiveness of FOs for paediatric flexible pes planus. Despite a number of
      methodological limitations, FOs show potential as a treatment method for children
      with flexible pes planus. PROSPERO REGISTRATION NUMBER: CRD42017057310.

PMID- 29451923
TI  - To what extent do potential conservation donors value community-aspects of
      conservation projects in low income countries?
AB  - There is a major gap in funding required for conservation, especially in low
      income countries. Given the significant contribution of taxpayers in
      industrialized countries to funding conservation overseas, and donations from
      membership organisation, understanding the preferences of ordinary people in a
      high income country for different attributes of conservation projects is valuable
      for future marketing of conservation. We conducted a discrete choice experiment
      with visitors to a UK zoo, while simultaneously conducting a revealed preference
      study through a real donation campaign on the same sample. Respondents showed the
      highest willingness to pay for projects that have local community involvement in
      management (95% confidence interval L9.82 to L15.83), and for improvement in
      threatened species populations (L2.97 - L13.87). Both of these were significantly
      larger than the willingness to pay for projects involving provision of
      alternative livelihoods, or improving the condition of conservation sites.
      Results of the simultaneous donation campaign showed that respondents were very
      willing to donate the suggested L1 or above donation (88% made a donation, n =
      1798); there was no effect of which of the two campaigns they were exposed to
      (threatened species management or community involvement in management). The small
      number of people who did not make a donation had a higher stated willingness to
      pay within the choice experiment, which may suggest hypothetical bias.
      Conservationists increasingly argue that conservation should include local
      communities in management (for both pragmatic and moral reasons). It is
      heartening that potential conservation donors seem to agree.

PMID- 29451922
TI  - Identifying classifier input signals to predict a cross-slope during transtibial
      amputee walking.
AB  - Advanced prosthetic foot designs often incorporate mechanisms that adapt to
      terrain changes in real-time to improve mobility. Early identification of terrain
      (e.g., cross-slopes) is critical to appropriate adaptation. This study suggests
      that a simple classifier based on linear discriminant analysis can accurately
      predict a cross-slope encountered (0 degrees , -15 degrees , 15 degrees ) using
      measurements from the residual limb, primarily from the prosthesis itself. The
      classifier was trained and tested offline using motion capture and in-pylon
      sensor data collected during walking trials in mid-swing and early stance.
      Residual limb kinematics, especially measurements from the foot, shank and ankle,
      successfully predicted the cross-slope terrain with high accuracy (99%). Although
      accuracy decreased when predictions were made for test data instead of the
      training data, the accuracy was still relatively high for one input signal set
      (>89%) and moderate for three others (>71%). This suggests that classifiers can
      be designed and generalized to be effective for new conditions and/or subjects.
      While measurements of shank acceleration and angular velocity from only in-pylon
      sensors were insufficient to accurately predict the cross-slope terrain, the
      addition of foot and ankle kinematics from motion capture data allowed accurate
      terrain prediction. Inversion angular velocity and foot vertical velocity were
      particularly useful. As in-pylon sensor data and shank kinematics from motion
      capture appeared interchangeable, combining foot and ankle kinematics from
      prosthesis-mounted sensors with shank kinematics from in-pylon sensors may
      provide enough information to accurately predict the terrain.

PMID- 29451924
TI  - Late effects awareness website for pediatric survivors of acute lymphocytic
      leukemia.
AB  - OBJECTIVES: Every day 43 children are newly diagnosed with cancer. Fortunately,
      almost 90% of these childhood cancer patients will survive. However, 60-90% of
      these survivors will experience late effects, health problems that occur months
      or years after treatment has ended. Late effects could occur as a result of the
      disease, its treatment, and patient-related factors. The two main objectives of
      this research are to: 1) Examine the existence of all web-based resources for
      childhood cancer survivors with acute lymphocytic leukemia which focus on medical
      and psychological aspects of late effects, and 2) Create an innovative website
      specifically designed to fill this void. MATERIALS AND METHODS: A systematic
      literature review, followed by input from >20 different organizations, resulted
      in the creation of LEAP3 AHEAD (Late Effects Awareness for Patients, Physicians
      and the Public; Advancing Health and Eliminating All Disparities), a multi
      dimensional website centering on late effects. RESULTS: An extensive review
      revealed 14 pediatric cancer websites, none of which focused exclusively on late
      effects. LEAP3 AHEAD is the first interactive website for acute lympocytic
      leukemia childhood cancer survivors and families, as well as physicians, and the
      public to: a) increase awareness about risks, detection, diagnosis, treatment,
      and prevention of medical and psychological late effects, b) provide suggestions
      to successfully reintegrate into schools, careers, and socially, and c) present
      opportunities including camps, scholarships, and pet therapy programs.
      CONCLUSION: LEAP3 AHEAD is the first national website to provide a comprehensive,
      accessible, affordable, and multi-dimensional resource for pediatricians,
      internists, nurse practitioners, psychologists, survivors and their families, as
      well as the public about late effects.

PMID- 29451926
TI  - Coronally Advanced Flap With or Without Subepithelial Connective Tissue Graft for
      the Treatment of Single Recession: 5-Year Outcomes from a Comparative Study.
AB  - Gingival recession can cause an esthetic impairment or dentin hypersensitivity
      due to root surface exposure to the oral cavity. These conditions may require
      specific surgical interventions to achieve root coverage. This controlled
      clinical trial on 20 subjects compared coronally advanced flap (CAF) technique
      and CAF plus subepithelial connective tissue graft (CTG) for the treatment of
      single maxillary gingival recession. Recession height (REC) and complete root
      coverage (CRC) were considered as primary outcomes. The residual REC was 2.90 +/-
      0.99 mm at baseline, 1.10 +/- 0.99 mm after 1 year, and 1.15 +/- 1.06 mm after 5
      years in the CAF group and 2.70 +/- 0.48 mm at baseline, 0.55 +/- 0.69 mm after 1
      year, and 0.44 +/- 0.62 mm after 5 years in the CAF + CTG group. The differences
      between groups at 5 years of follow-up was statistically significant. CRC was
      obtained in 60% of teeth in the CAF group and in 70% of teeth in the CAF + CTG
      group at the 5-year follow-up. The results showed a significant difference
      between CAF and CAF + CTG techniques for the treatment of single recession with
      regard to REC; no significant difference was found in the percentage of teeth
      presenting CRC after 5 years.

PMID- 29451925
TI  - The impact of "Option B" on HIV transmission from mother to child in Rwanda: An
      interrupted time series analysis.
AB  - BACKGROUND: Nearly a quarter of a million children have acquired HIV, prompting
      the implementation of new protocols-Option B and B+-for treating HIV+ pregnant
      women. While efficacy has been demonstrated in randomized trials, there is
      limited real-world evidence on the impact of these changes. Using longitudinal,
      routinely collected data we assessed the impact of the adoption of WHO Option B
      in Rwanda on mother to infant transmission. METHODS: We used interrupted time
      series analysis to evaluate the impact of Option B on mother-to-child HIV
      transmission in Rwanda. Our primary outcome was the proportion of HIV tests in
      infants with positive results at six weeks of age. We included data for 20 months
      before and 22 months after the 2010 policy change. RESULTS: Of the 15,830 HIV
      tests conducted during our study period, 392 tested positive. We found a
      significant decrease in both the level (-2.08 positive tests per 100 tests
      conducted, 95% CI: -2.71 to -1.45, p < 0.001) and trend (-0.11 positive tests per
      100 tests conducted per month, 95% CI: -0.16 to -0.07, p < 0.001) of test
      positivity. This represents an estimated 297 fewer children born without HIV in
      the post-policy period or a 46% reduction in HIV transmission from mother to
      child. CONCLUSIONS: The adoption of Option B in Rwanda contributed to an
      immediate decrease in the rate of HIV transmission from mother to child. This
      suggests other countries may benefit from adopting these WHO guidelines.

PMID- 29451927
TI  - A Retrospective Tomographic and Histologic Analysis of Horizontal Bone
      Augmentation in Maxillary Atrophic Ridges Using Resorbable Membrane with
      Anorganic Bovine Bone-Derived Mineral and Plasma Rich in Growth Factors.
AB  - A total of six patients treated from 2010 to 2014, having a knife-edge ridge
      (Cawood-Howell Class IV resorbed ridges) and requiring an implant-prosthetic
      rehabilitation, were selected. Tomographic measurement of the edentulous ridges
      was performed before grafting and after implant placement. At 6 months postgraft,
      a total of 41 implants had been inserted, 17 in the posterior region, 12 in the
      central region, and 12 in the anterior region. No surgical or healing
      complications were recorded, and the prostheses were loaded 6 to 9 months after
      implant placement. The tomographic measurements demonstrated an increased area in
      all the sites where bone augmentation had been performed, corresponding to 11.1%
      in the anterior region, 94.7% in the central region, and 760.2% in the posterior
      region. Histology was performed in 2 patients, one at 1 year and the other at 5
      years postgrafting, and demonstrated the presence of mature lamellar bone tissue
      and newly formed bone without morphologic signs of necrosis or inflammation and a
      reduction of 50% to 30% of the grafted material. Although this study included a
      small number of clinical cases, it demonstrated how management of the atrophic
      maxillary ridge, with the goal of implant placement, may be handled using a
      technique that requires a single anorganic bovine bone-derived mineral treatment
      combined with a plasma rich in growth factors and resorbable collagen membrane.

PMID- 29451928
TI  - A Novel Connective Tissue Graft Harvesting Technique: The Ring Method.
AB  - The aim of these case reports was to introduce a simplified novel connective
      tissue graft (CTG) harvesting technique, the ring method, which could be used in
      the maxillary tuberosity area in particular. A special CTG harvesting punch was
      fabricated to obtain a ring-shaped CTG that had a uniform thickness. The ring
      graft was then used for peri-implant soft tissue augmentation with successful
      clinical outcomes. The ring method is a technically insensitive and minimally
      invasive surgical procedure that provides a certain amount of CTG for various
      periodontal plastic surgical interventions.

PMID- 29451929
TI  - Natural Tooth as the Permanent Reconstruction After Immediate Implantation in the
      Esthetic Zone of Periodontally Compromised Patients.
AB  - This case series describes a treatment method in which the natural tooth was used
      as the temporary and permanent reconstruction after immediate implantation in the
      esthetic zone of periodontally compromised patients. Five patients with a
      hopeless tooth in the esthetic zone due to periodontal causes were included. The
      tooth was extracted, and immediate implantation protocol was followed. The
      extracted tooth was adapted over a temporary abutment during the osseointegration
      period, and the same tooth served as the final prosthetic reconstruction with a
      customized zirconia abutment. Esthetic outcome was satisfactory to the patients,
      and no biologic or prosthetic complications were observed up to 3 years. The
      technique could be recommended, especially in the esthetic area of periodontally
      compromised patients who have intact clinical crowns.

PMID- 29451930
TI  - The Effect of Implant Abutment Design on Long-Term Soft Tissue Stability: A
      Clinical Case Report.
AB  - Prosthetic rehabilitation of malpositioned anterior dental implants can be
      challenging. Interdisciplinary treatment planning and precise execution of
      biologically acceptable prosthetic and surgical protocols are essential to
      achieve optimal esthetic results and while avoiding and managing esthetic
      complications. This case study focuses on the restorative aspect. Two sets of
      custom gold abutments were used prior to and following surgical correction of a
      pre-existing soft and hard tissue ridge defect surrounding maxillary central
      incisor implant restorations. A stable and esthetically pleasing result was
      documented 7 years following delivery of definitive esthetic central incisor
      implant restorations.

PMID- 29451931
TI  - Nonsurgical Management of Peri-implant Bone Loss Induced by Residual Cement:
      Retrospective Analysis of Six Cases.
AB  - This report presents six consecutive cases of peri-implantitis associated with
      residual methacrylate cement. The cases responded to cement removal and
      disinfection procedures. Six patients, each presenting one methacrylate cement
      retained implant restoration and showing peri-implant inflammation and bone loss,
      were treated. All the cases were negative for bleeding on probing after 6 weeks,
      and this was maintained at 1 year of follow-up from nonsurgical therapy and crown
      refixation with alternative and resorbable cement. The treatment effectively
      solved the inflammation and led to complete restoration ad integrum, as evaluated
      clinically and radiographically, after 1 year.

PMID- 29451932
TI  - In Vitro Screening of the Antibacterial and Anti-Candida Properties of Crushed
      Nonantimicrobial Drugs Frequently Prescribed in Nursing Homes.
AB  - Frail older adults often experience swallowing disorders, prompting nursing staff
      to crush tablets, open capsules, and mix drugs into their meals or gelled water.
      However, crushing drugs can lead to pharmacological and gustatory problems. As
      crushed drugs can stay in prolonged contact with oral microbial biofilm, the
      current study aimed to investigate their antimicrobial properties. Crushed drugs
      were diluted in 1 mL of isotonic water and assayed in vitro for: (a) growth
      inhibition of five bacterial strains and Candida albicans by the diffusion
      method; (b) inhibition of Streptococcus salivarius and C. albicans biofilm
      formation; and (c) elimination of a preformed biofilm of S. salivarius and C.
      albicans after 5-minute contact. Eight of 29 crushed drugs inhibited bacterial
      and/or fungal growth on agar plates. Twenty-eight of 29 crushed drugs reduced the
      total biomass when incubated with S. salivarius, and 28 of 29 crushed drugs
      inhibited C. albicans biofilm formation. Preformed biomass was reduced by >=25%
      by seven of 29 drugs. Crushed drugs may unbalance oral ecosystems and contribute
      to oral inflammation. [Res Gerontol Nurs. 2018; 11(2):82-90.].

PMID- 29451933
TI  - Depressive Symptoms and Physical Frailty in Older Adults With Chronic Heart
      Failure: A Cross-Sectional Study.
AB  - Depressive symptoms and physical frailty have been reported to be predictive of
      adverse outcomes in individuals with heart failure (HF). Depressive symptoms
      could be a predisposing factor of physical frailty in older adults. Despite the
      high prevalence of HF, few studies on the relationship between these two factors
      have been performed in older adults with HF. To identify the relationship between
      depressive symptoms and physical frailty in HF, 190 older adults with HF were
      recruited from an outpatient clinic at a tertiary hospital in South Korea. The
      prevalence of depressive symptoms and physical frailty in older adults with HF
      was 30% (n = 57) and 61.6% (n = 117), respectively. Multivariate logistic
      regression revealed that depressive symptoms most strongly increased the risk of
      physical frailty after adjusting for confounding factors. Early detection of
      depressive symptoms might be useful to identify the status of physical frailty at
      the illness trajectories of HF in older adults and for judicious allocation of
      disease management strategies. [Res Gerontol Nurs. 2018; 11(3):160-168.].

PMID- 29451934
TI  - Development of a Self-Report Checklist to Assess Dementia Care by Nurses in
      Hospital Settings.
AB  - Nurses working at general hospitals face difficulties in providing dementia care.
      The current study examined aged care nurses' dementia care practices in the
      hospital setting and developed a dementia care checklist that nurses can use to
      review their own care practice. A self-administered questionnaire was given to
      676 participants; responses were collected from 595 participants. Exploratory
      factor analysis identified six factors (e.g., patient understanding prompted by
      concern and interest for the patient, respect for patients' voluntary behavior,
      early detection of abnormalities) among the questionnaire's 28 items. This
      analysis provided a framework for the checklist and verified that it had
      satisfactory internal consistency and construct validity. The frequency of care
      practices varied with participants' knowledge of dementia care requirements,
      satisfaction with their own dementia care practice, confidence in their ability
      to judge patients' physical condition, and cooperation with colleagues. This
      checklist might improve dementia care in hospital settings. [Res Gerontol Nurs.
      2018; 11(2):91-102.].

PMID- 29451935
TI  - Economic Analysis of Anatomic Plating Versus Tubular Plating for the Treatment of
      Fibula Fractures.
AB  - Ankle fractures are among the most common injuries requiring operative
      management. Implant choices include one-third tubular plates and anatomically
      precontoured plates. Although cadaveric studies have not revealed biomechanical
      differences between various plate constructs, there are substantial cost
      differences. This study sought to characterize the economic implications of
      implant choice. A retrospective review was undertaken of 201 consecutive patients
      with operatively treated OTA type 44B and 44C ankles. A Nationwide Inpatient
      Sample query was performed to estimate the incidence of ankle fractures requiring
      fibular plating, and a Monte Carlo simulation was conducted with the estimated at
      risk US population for associated plate-specific costs. The authors estimated an
      annual incidence of operatively treated ankle fractures in the United States of
      59,029. The average cost was $90.86 (95% confidence interval, $90.84-$90.87) for
      a one-third tubular plate vs $746.97 (95% confidence interval, $746.55-$747.39)
      for an anatomic plate. Across the United States, use of only one-third tubular
      plating over anatomic plating would result in statistically significant savings
      of $38,729,517 (95% confidence interval, $38,704,773-$38,754,261; P<.0001).
      General use of one-third tubular plating instead of anatomic plating whenever
      possible for fibula fractures could result in cost savings of up to nearly $40
      million annually in the United States. Unless clinically justifiable on a per
      case basis, or until the advent of studies showing substantial clinical benefit,
      there currently is no reason for the increased expense from widespread use of
      anatomic plating for fractures amenable to one-third tubular plating.
      [Orthopedics. 2018; 41(2):e252-e256.].

PMID- 29451936
TI  - Subtle Lisfranc Injuries: A Topical Review and Modification of the Classification
      System.
AB  - Lisfranc injuries are relatively uncommon. No specific incidence of subtle
      injuries has been reported; however, almost one-third are missed on initial
      review. These missed injuries are a common cause of litigation. Although seen in
      high-energy injuries with direct application of forces, they are also associated
      with lower-energy indirect mechanisms, often on the athletic field. This article
      provides a topical review of subtle Lisfranc disruptions, focusing on
      contemporary perspectives, and describes a modification to the most prevalent
      classification system. [Orthopedics. 2018; 41(2):e168-e175.].

PMID- 29451937
TI  - Custom Triflange Acetabular Components for Large Acetabular Defects: Minimum 10
      Year Follow-up.
AB  - Compromise of bony support presents a difficult problem in acetabular revision
      surgery. Although various methods have been proposed to cope with this problem,
      they have had variable results and little long-term follow-up. The authors
      reviewed the results of 37 patients undergoing custom triflange revision surgery.
      Two patients were lost to follow-up, leaving 35 patients with minimum 10-year
      clinical and radiographic follow-up. Thirty-two (91%) of 35 components were
      unrevised and functioning well at minimum 10-year follow-up. One component placed
      for pelvic discontinuity loosened at 12 years after surgery but was converted to
      a conventional total hip. One component had failure of 3 ischial screws at 6
      months; however, at 11 years, the patient had no additional clinical or
      radiographic evidence of loosening. The average Harris hip score was 28
      preoperatively and 90 postoperatively. Two components (6%) were removed for
      infection. There were no dislocations, fractures, or nerve injuries. Revision of
      large acetabular defects with a custom triflange component resulted in reliably
      good to excellent results at minimum 10-year follow-up. [Orthopedics. 2018;
      41(3):e316-e320.].

PMID- 29451938
TI  - The Management of Cerebrospinal Fluid Leak After Anterior Cervical Decompression
      Surgery.
AB  - Cerebrospinal fluid (CSF) leak is a rare but potentially troublesome and
      occasionally catastrophic complication after anterior cervical decompression
      surgery. There is limited literature describing this complication, and the
      management of CSF leak varies. The aim of this study was to retrospectively
      review the treatment of cases with CSF leak and develop a management algorithm. A
      series of 14 patients with CSF leak from January 2011 to May 2016 were included
      in this study. Their characteristics, management of CSF leak, and outcomes were
      documented. There were 5 male and 9 female patients. Mean age at surgery was
      57.1+/-9.9 years (range, 37-76 years). All instances of CSF leak, except 1 noted
      postoperatively, were indirectly repaired intraoperatively. A closed straight
      wound drain was placed for all patients. A lumbar subarachnoid drain was placed
      immediately after surgery in 4 patients and postoperatively in 7 patients. In 1
      patient, lumbar drain placement was unsuccessful. In 2 additional patients, the
      surgeon decided not to place a lumbar drain. One patient developed meningitis and
      recovered after antibiotic therapy with meropenem and vancomycin. Another patient
      had a deep wound infection and required a revision surgery. Wound drains and
      lumbar drains should be immediately considered when CSF leak is identified.
      Antibiotics also should be considered to prevent intradural infection.
      [Orthopedics. 2018; 41(2):e283-e288.].

PMID- 29451939
TI  - Reverse Shoulder Arthroplasty in the Weight-Bearing Versus Non-Weight-Bearing
      Shoulder: Mid-term Outcomes With Minimum 5-Year Follow-up.
AB  - This retrospective review evaluated the mid-term outcomes of cemented reverse
      shoulder arthroplasty in patients who use the shoulder for weight bearing (WB) vs
      non-weight-bearing (NWB) patients. Twenty-five shoulders of 21 patients who used
      their upper extremity for WB (WB group) were treated with cemented reverse
      shoulder arthroplasty and followed for a minimum of 5 years postoperatively
      (average, 73 months). Seventy-five consecutive shoulders of 72 patients who were
      NWB (NWB group) were treated and matched for duration of follow-up (average, 72
      months) to serve as a control group. Patients were followed clinically and
      radiographically. There were no statistically significant differences between the
      WB group and the NWB group regarding final outcome scores or range of motion.
      Patient satisfaction was similar between the WB group (92%) and the NWB group
      (94%). The scapular notching rate was 20% in the WB group compared with 5% in the
      NWB group (P=.041). Humeral loosening occurred in 12% of the WB group vs 0% of
      the NWB group (P=.014). The complication rate was higher in the WB group than in
      the NWB group (12% vs 4%). The WB group and the NWB group had similar outcome
      scores, range of motion improvements, and patient satisfaction after reverse
      shoulder arthroplasty. At mid-term follow-up, the WB group had a higher scapular
      notching rate, humeral loosening rate, and complication rate than the NWB group.
      [Orthopedics. 2018; 41(3):e328-e333.].

PMID- 29451940
TI  - Patient Factors Associated With Methicillin-Resistant Staphylococcus aureus
      Septic Arthritis in Children.
AB  - Staphylococcus aureus is the most common causative organism in pediatric septic
      arthritis, with methicillin-resistant Staphylococcus aureus (MRSA) being
      responsible for a significant portion of these infections. Early identification
      and initiation of proper treatment may improve outcomes by minimizing potential
      morbidity. The purpose of this study was to identify variables obtained on
      initial patient presentation associated with MRSA septic arthritis. Sixteen
      factors were retrospectively evaluated in 109 consecutive pediatric patients
      diagnosed with culture-confirmed septic arthritis. Graphical and logistical
      regression analyses were employed to determine factors independently predictive
      of MRSA septic arthritis. Twenty-seven (25%) patients had MRSA and 82 (75%) had
      non-MRSA septic arthritis. C-reactive protein of 13.7 mg/L or greater, duration
      of symptoms of 4 days or more, heart rate of 126 beats per minute or greater, and
      absolute neutrophil count of 8.72*103 cells/uL or greater were associated with
      MRSA septic arthritis. Ultimately, 98% of patients with 1 or no risk factors had
      non-MRSA and 96% of patients with MRSA septic arthritis had 2 or more positive
      risk factors. Elevated C-reactive protein, duration of symptoms, heart rate, and
      absolute neutrophil count are predictive of MRSA infection in the setting of
      pediatric septic arthritis and can be obtained on initial evaluation. In patients
      for whom there is concern for MRSA infection, this may guide more expedient
      treatment, such as early initiation of contact precautions and appropriate
      antibiotic therapy before culture results become available. [Orthopedics. 2018;
      41(2):e277-e282.].

PMID- 29451941
TI  - Return to Work After Anatomic Total Shoulder Arthroplasty for Patients 55 Years
      and Younger at Average 5-Year Follow-up.
AB  - As the number of anatomic total shoulder arthroplasties performed on younger
      patients continues to grow, return to work after surgery becomes increasingly
      important. The purpose of this study was to evaluate the ability of anatomic
      total shoulder arthroplasty to return patients 55 years or younger to work
      postoperatively. A retrospective review was performed of consecutive anatomic
      total shoulder arthroplasty patients. Inclusion criteria were age 55 years or
      younger at surgery, greater than 2 years of follow-up, and employment within 3
      years of surgery. Employment was stratified by intensity of work (sedentary,
      light, moderate, or heavy). Return to work status and time out of work were also
      evaluated. Fifty-two patients worked before surgery. Average age was 48.4 years,
      with average follow-up of 5.4 years. Seventy-three percent were male, and average
      body mass index was 28.0 kg/m2. Average visual analog scale score improved from
      5.5 to 0.9 (P<.0001) and American Shoulder and Elbow Society score improved from
      39.9 to 88.3 (P<.0001). Forty-eight (92%) of 52 returned to work postoperatively
      after an average of 2.1 months. When stratified by intensity, all patients with
      sedentary, light, or moderate work returned, whereas 64% returned to heavy work
      (P<.01). Eighty-seven percent were satisfied to very satisfied after surgery. In
      summary, most patients (92%) who undergo anatomic total shoulder arthroplasty at
      55 years or younger return to work, on average, 2.1 months after surgery.
      [Orthopedics. 2018; 41(3):e310-e315.].

PMID- 29451942
TI  - Incidence of and Risk Factors for Knee Collateral Ligament Injuries With Proximal
      Tibia Fractures: A Study of 32,441 Patients.
AB  - Proximal tibia fractures are associated with concurrent collateral ligament
      injuries. Failure to recognize these injuries may lead to chronic knee
      instability. The purpose of this study was to identify risk factors for
      concurrent collateral ligament injuries with proximal tibia fractures and their
      association with inpatient outcomes. A total of 32,441 patients with proximal
      tibia fractures were identified in the 2011-2012 National Trauma Data Bank. A
      total of 1445 (4.5%) had collateral ligament injuries, 794 (2.4%) had injuries to
      both collateral ligaments, 456 (1.4%) had a medial collateral ligament injury
      only, and 195 (0.6%) had a lateral collateral ligament injury only. On
      multivariate analysis, risk factors found to be associated with collateral
      ligament injuries included distal femur fracture (odds ratio, 2.1), pedestrian
      struck by motor vehicle (odds ratio, 2.0), obesity (odds ratio, 1.6), young age
      (odds ratio, 1.9 for 18 to 29 years vs 40 to 49 years), motorcycle accident (odds
      ratio, 1.5), and Injury Severity Score of 20 or higher (odds ratio, 1.4). In
      addition, patients with simultaneous injuries to both collateral ligaments had
      higher odds of inpatient adverse events (odds ratio, 1.51) and longer hospital
      stay (mean, 2.27 days longer). The risk factors reported by this study can be
      used to identify patients with proximal tibia fractures who may warrant more
      careful and thorough evaluation and imaging of their knee collateral ligaments.
      [Orthopedics. 2018; 41(2):e268-e276.].

PMID- 29451943
TI  - Dual Diagnosis and Total Hip Arthroplasty.
AB  - The co-occurrence of a mental illness and a substance abuse disorder (SUD) is
      common and has been referred to as a "dual diagnosis" (DD). Although studies have
      independently investigated mental illness alone and SUD alone, few have examined
      the effects of these entities combined on complications. A search of the Medicare
      database from 2005 to 2012 identified 2000 DD patients who underwent total hip
      arthroplasty (THA). They were compared with 86,976 patients with mental illness
      only and 590,689 controls (no mental illness or SUD). Medical comorbidities and
      postoperative complications at 30-day, 90-day, and minimum 2-year time points
      were analyzed. There was a significant increase (P<.001) in 7 (53.8%) of 13
      recorded postoperative medical complications, including acute renal failure (odds
      ratio [OR], 1.78), postoperative anemia (OR, 1.31), and blood transfusion (OR,
      1.24), at the 90-day time point. In addition, there was a statistically
      significant increase overall in periprosthetic infection (periprosthetic joint
      infection OR, 4.30; P<.001), periprosthetic fracture (OR, 2.80; P<.001),
      dislocation (OR, 6.38; P<.001), and the need for THA revision (OR, 3.58; P<.001).
      When compared with patients with mental illness only, DD patients remained at
      significantly (P<.001) increased risk for 90-day and overall postoperative
      surgical complications, including dislocation, periprosthetic joint infection,
      and THA revision. Patients with a DD were at significant risk for perioperative
      complications compared with both control patients and patients with mental
      illness only. Studies investigating only psychiatric disease or only SUD may miss
      a vulnerable cohort. Further investigation is needed to exactly define to what
      extent DD amplifies complication rates. [Orthopedics. 2018; 41(3):e321-e327.].

PMID- 29451944
TI  - Total Hip Arthroplasty in Patients With Avascular Necrosis After Hematopoietic
      Stem Cell Transplantation.
AB  - The immunosuppressive regimens required for hematopoietic stem cell
      transplantation predispose recipients to complications, including avascular
      necrosis. Cancer-related comorbidities, immunosuppression, and poor bone quality
      theoretically increase the risk for perioperative medical complications,
      infection, and implant-related complications in total joint arthroplasty. This
      study reviewed 20 primary total hip arthroplasties for avascular necrosis in 14
      patients. Outcomes were assessed at routine clinical visits and Harris hip scores
      were calculated. Follow-up radiographs were evaluated for component malposition,
      loosening, polyethylene wear, and osteolysis. Average follow-up was 44.5 months
      for all patients. Postoperative clinical follow-up revealed good to excellent
      outcomes, with significant improvement in functional outcome scores. There were
      no periprosthetic infections or revisions for aseptic loosening. There was 1
      dislocation on postoperative day 40, which was treated successfully with a closed
      reduction. Two patients with a prior history of venous thromboembolism developed
      a pulmonary embolus on postoperative day 13 and 77, respectively. Four patients
      died several months to years after arthroplasty of complications unrelated to the
      surgical procedure. Total hip arthroplasty can both be safely performed and
      greatly improve quality of life in recipients of hematopoietic stem cell
      transplantation who develop avascular necrosis. However, prolonged venous
      thromboembolism prophylaxis should be carefully considered in this high-risk
      patient population. [Orthopedics. 2018; 41(2):e257-e261.].

PMID- 29451945
TI  - The Effects of Platelet-Rich Plasma and Activated Collagen on Wound Healing in
      Primary Total Joint Arthroplasty.
AB  - Wound healing remains a concern in primary total joint arthroplasty, given the
      risk of deep infections arising from hematomas, wound separations, and
      superficial infections. If wound additives can prevent these early complications,
      their universal application would be cost-effective. This study examined whether
      2 wound additives, platelet-rich plasma (PRP) and activated collagen, would
      improve postoperative wound healing and reduce complications in primary total
      joint arthroplasty. A prospective, randomized controlled study was conducted
      using 3 cohorts with 30 patients each (group 1: PRP; group 2: activated collagen;
      and group 3: control). These patients were examined at 2 and 6 weeks
      postoperatively, at which time the following data were recorded: 6 wound
      measurements, total postoperative blood loss, complications of superficial
      infections, and reoperations. The PRP and the activated collagen groups showed
      early improvement in 3 of the 6 wound scores at 2 weeks, but these early results
      were not present at 6 weeks. In addition, there was a statistically significant
      reduction in blood loss in both the PRP and the activated collagen groups, as
      compared with the control group. Furthermore, high-risk patients had a
      statistically significant reduction in total complication rates in both the PRP
      and the activated collagen groups, as compared with the control group. On the
      basis of this study, these additives are not recommended for routine primary
      joint arthroplasty; however, the data suggest possible benefits for high-risk
      patients and those for whom blood loss may be an issue. [Orthopedics. 2018;
      41(2):e262-e267.].

PMID- 29451946
TI  - First experience in Switzerland in Phe508del homozygous cystic fibrosis patients
      with end-stage pulmonary disease enrolled in a lumacaftor-ivacaftor therapy trial
      - preliminary results.
AB  - AIMS OF THE STUDY: Cystic fibrosis is the most common genetic disorder in
      Caucasians. The combination of the cystic fibrosis transmembrane conductance
      regulator (CFTR) corrector lumacaftor / potentiator ivacaftor (LUM/IVA) has been
      shown to increase forced expiratory volume in 1 second (FEV1) moderately, but
      predominantly reduce acute exacerbation rate (AER) in Phe508del homozygous cystic
      fibrosis patients; however, patients with FEV1 <40% predicted were excluded from
      studies. We used LUM/IVA on a "compassionate use" basis in cystic fibrosis
      patients with end-stage pulmonary disease. Our aim was to evaluate if this
      patient cohort tolerates LUM/IVA treatment and if there is clinical
      stabilisation. Lung transplantation (LTX) is the ultimate treatment option for
      these patients despite maximal therapy. If LTX candidates stabilise clinically,
      conditions for LTX, when it is indicated, improve. This is particularly important
      in countries such as Switzerland with a low organ donation rate and long waiting
      times for suitable donor organs. METHODS: We included all patients from the Adult
      Cystic Fibrosis Centre at the University Hospital Zurich with Phe508del
      homozygous genotype and a predicted FEV1 <40% or being evaluated or already
      listed for LTX. Clinical outcome data comprised AER, 6-minute walking distance (6
      MWD), FEV1, forced vital capacity (FVC), mid-expiratory flow (MEF 25-75%), sweat
      chloride, body mass index (BMI) and quality of life. Respiratory-related adverse
      events (RAEs) were recorded. LUM/IVA treatment was initiated at a low dose and
      the dose increased stepwise. RESULTS: Twenty patients were on trial with LUM/IVA;
      at the cut-off date, 6-month follow-up was complete for 10 patients. RAEs were
      severe and occurred early. The dropout rate due to RAE or lack of clinical
      success was 20%. Median AER decreased from 2.5 in the 6 months pre-treatment to 1
      during the observation period. FEV1 increased from 32 to 34.5% predicted, p =
      0.292. The 6-MWD increased by a median 33 m (p = 0.6086). Sweat chloride
      decreased significantly by a median of 25 mmol/l (p = 0.0003). Median BMI
      increased from 19 to 19.9 kg/m2 (p = 0.1488). At the cut-off, three previously
      listed patients were paused on the transplant waiting list. CONCLUSION: Phe508del
      homozygous cystic fibrosis patients with end-stage pulmonary disease tolerated
      LUM/IVA, although RAEs occurred early and were severe. This positive finding was
      probably due to the stepwise dose increases. There was clinical benefit mainly
      from reduction in AER and stabilisation of lung function. We propose that all
      suitable Phe508del homozygous cystic fibrosis patients with end-stage pulmonary
      disease should have a trial of LUM/IVA treatment in experienced centres.

PMID- 29451947
TI  - A wild bootstrap approach for the Aalen-Johansen estimator.
AB  - We suggest a wild bootstrap resampling technique for nonparametric inference on
      transition probabilities in a general time-inhomogeneous Markov multistate model.
      We first approximate the limiting distribution of the Nelson-Aalen estimator by
      repeatedly generating standard normal wild bootstrap variates, while the data is
      kept fixed. Next, a transformation using a functional delta method argument is
      applied. The approach is conceptually easier than direct resampling for the
      transition probabilities. It is used to investigate a non-standard time-to-event
      outcome, currently being alive without immunosuppressive treatment, with data
      from a recent study of prophylactic treatment in allogeneic transplanted leukemia
      patients. Due to non-monotonic outcome probabilities in time, neither standard
      survival nor competing risks techniques apply, which highlights the need for the
      present methodology. Finite sample performance of time-simultaneous confidence
      bands for the outcome probabilities is assessed in an extensive simulation study
      motivated by the clinical trial data. Example code is provided in the web-based
      Supplementary Materials.

PMID- 29451948
TI  - Duration of maternal mental health-related outcomes after an infant's death: A
      retrospective matched cohort study using linkable administrative data.
AB  - BACKGROUND: Mothers have increased mental illness such as anxiety and depression
      after the death of a child. We examine the duration of this worsening of mental
      health. METHODS: The mental health of all mothers who experience the death of an
      infant (< 1 years old) in Manitoba, Canada between April 1, 1999 and March 31,
      2011 (n = 534) is examined in the 4 years leading up to, and the 4 years
      following, the death of their child. Mental health-related outcomes of these
      mothers are compared with a matched (3:1) cohort of mothers who did not
      experience the death of a child (n = 1,602). Three mental health-related outcomes
      are examined: depression diagnoses, anxiety diagnoses, and use of psychotropic
      medications. RESULTS: Compared with mothers who did not experience the death of a
      child, mothers experiencing this event had higher rates of anxiety diagnoses and
      psychotropic prescriptions starting 6 months before the death. Elevated rates of
      anxiety continued for the first year and elevated rates of psychotropic
      prescriptions continued for 6 months after the death of the child. Mothers who
      experienced the death of a child had higher rates of depression diagnoses in the
      year after the death. Relative rates (RR) of depression (RR = 4.94), anxiety (RR
      = 2.21), and psychotropic medication use (RR = 3.18) were highest in the 6 months
      after the child's death. CONCLUSIONS: Elevated rates of depression, anxiety, and
      psychotropic medication use after the death of a child end within 1 year of the
      child's death.

PMID- 29451949
TI  - Impact of sheath size and hemostasis time on radial artery patency after
      transradial coronary angiography and intervention in Japanese and non-Japanese
      patients: A substudy from RAP and BEAT (Radial Artery Patency and Bleeding,
      Efficacy, Adverse evenT) randomized multicenter trial.
AB  - BACKGROUND: During transradial (TR) access, it remains unclear whether
      differences in baseline patients characteristics and hemostasis care impact the
      rate of radial artery occlusion (RAO). We sought to compare the rate of RAO after
      TR access with the 6 French(Fr) Glidesheath Slender (GSS6Fr, Terumo, Japan) or a
      standard 5 Fr sheath in Japanese and non-Japanese patients. METHODS AND RESULTS:
      The Radial Artery Patency and Bleeding, Efficacy, Adverse evenT (RAP and BEAT)
      trial randomized 1,836 patients undergoing TR coronary angiography and/or
      interventions to receive the GSS6Fr or the standard 5 Fr Glidesheath (GS5Fr,
      Terumo, Japan). Out of this study population, 1,087 were Japanese patients and
      751 non-Japanese patients. The overall incidence of RAO was significantly higher
      in Japanese patients (3.6% vs. 1.2%, P = 0.002). Use of GSS6Fr was associated
      with higher rates of RAO than GS5Fr in Japanese patients (5% vs. 2.2%, P = 0.02)
      and with similar RAO rates in non-Japanese patients (1.3 vs. 1.1%, P = 1). The
      mean hemostasis time was significantly longer in Japanese patients (378 +/- 253
      vs. 159 +/- 136 min, P < 0.001) and more Japanese patients had a hemostasis time
      of more than 6 hr (16.2% vs. 4.9%, P < 0.0001). Longer hemostasis time was an
      independent predictor of RAO (OR per additional hour 1.070, 95% CI 1.008-1.136, P
      = 0.03). CONCLUSIONS: Use of GSS6Fr was associated with a higher rate of RAO than
      a standard 5 Fr sheath in Japanese patients but not in non-Japanese patients.
      Whether improvement in post-procedural care and reduced hemostasis time could
      impact the incidence of RAO in Japanese patients should be further assessed.

PMID- 29451950
TI  - Intrinsic changes of left ventricular function in patients with Behcet disease
      and comparison according to systemic disease activity.
AB  - PURPOSE: Although cardiac manifestation of Behcet disease (BD) has been described
      in sporadic reports, its timely diagnosis remains difficult. The objective of
      this study was to describe early cardiac manifestations of BD. We also performed
      a comprehensive classification of systemic BD activity and compared their cardiac
      manifestations. METHODS: A prospective screening using speckle tracking
      echocardiography was performed in 85 patients with BD who had no history of heart
      disease. After excluding subjects with left ventricular (LV) ejection fraction
      (LVEF) <50% (n = 1), atrial fibrillation (n = 2), or inadequate echocardiographic
      images (n = 1), we analyzed their clinical and echocardiographic parameters
      including LV global longitudinal strains (GLS) and compared them with those of an
      age- and gender-matched control group (n = 145). Systemic BD activity was
      classified as minimal (Group A), controlled (Group B), and active (Group C).
      RESULTS: In 81 study patients (59 females, age of 51 +/- 11 years),
      echocardiography revealed a mean LVEF of 64 +/- 5% without any significant
      valvular dysfunction or aortic aneurysm. Although there was no difference in LVEF
      between the control group and the patient group, the patient group showed
      significant reduction in GLS (-17.1 +/- 2.9% vs -20.8 +/- 2.2%, P < .001). Groups
      A (n = 21, 26%), B (n = 47, 58%), and C (n = 13, 58%) consistently showed
      reduction in GLS compared with the control group. However, there was no
      significant difference in cardiac manifestations among these groups according to
      systemic disease activity. CONCLUSION: Patients with BD present intrinsic LV
      dysfunction despite no apparent abnormality on routine echocardiography. However,
      their cardiac manifestations are not proportional to systemic BD activity.

PMID- 29451951
TI  - Time course and clinical characterization of cisplatin-induced ototoxicity after
      treatment for nasopharyngeal carcinoma in a South East Asian population.
AB  - BACKGROUND: The purpose of this study was to characterize the clinical course of
      hearing loss in patients with nasopharyngeal carcinoma (NPC) and the clinical
      factors affecting its severity. METHODS: The time course of hearing loss in
      patients with NPC was assessed using threshold shift from baseline and Common
      Terminology Criteria for Adverse Events (CTCAE) grade. RESULTS: In the
      chemoradiotherapy (CRT) groups, the threshold shift was significantly higher from
      3 months at 4 kHz (P = 2.30 * 10-9 , concurrent CRT only) but not within 2 years
      posttreatment in the radiotherapy (RT) group. The CRT groups had worse CTCAE
      grades than the RT group (percentage of latest CTCAE grade >=1: 64.9% vs 29.0%,
      respectively). Cumulative cisplatin dose and cochlear RT dose significantly
      affects threshold shifts, especially at high frequencies. CONCLUSION: Although
      cisplatin led to high frequency hearing impairment from about 3 months
      posttreatment, RT conferred no significant hearing impairment in the first 2
      years.

PMID- 29451952
TI  - One-Step Synthesis of Hybrid Core-Shell Metal-Organic Frameworks.
AB  - Epitaxial growth of MOF-on-MOF composite is an evolving research topic in the
      quest for multifunctional materials. In previously reported methods, the core
      shell MOFs were synthesized via a stepwise strategy that involved growing the
      shell-MOFs on top of the preformed core-MOFs with matched lattice parameters.
      However, the inconvenient stepwise synthesis and the strict lattice-matching
      requirement have limited the preparation of core-shell MOFs. Herein, we
      demonstrate that hybrid core-shell MOFs with mismatching lattices can be
      synthesized under the guidance of nucleation kinetic analysis. A series of MOF
      composites with mesoporous core and microporous shell were constructed and
      characterized by optical microscopy, powder X-ray diffraction, gas sorption
      measurement, and scanning electron microscopy. Isoreticular expansion of
      microporous shells and orthogonal modification of the core was realized to
      produce multifunctional MOF composites, which acted as size selective catalysts
      for olefin epoxidation with high activity and selectivity.

PMID- 29451953
TI  - Using quantitative tissue phenotype to assess the margins of surgical samples
      from a pan-Canadian surgery study.
AB  - BACKGROUND: The purpose of this study was to use quantitative tissue phenotype
      (QTP) to assess the surgical margins to examine if a fluorescence visualization
      guided surgical approach produces a shift in the surgical field by sparing normal
      tissue while catching high-risk tissue. METHODS: Using our QTP to calculate the
      degree of nuclear chromatin abnormalities, Nuclear Phenotypic Score (NPS), we
      analyzed 1290 biopsy specimens taken from surgical samples of 248 patients
      enrolled in the Efficacy of Optically-guided Surgery in the Management of Early
      staged Oral Cancer (COOLS) trial. Multiple margin specimens were collected from
      each surgical specimen according to the presence of fluorescence visualization
      alterations and the distance to the surgical margins. RESULTS: The NPS in
      fluorescence visualization-altered (fluorescence visualization-positive) samples
      was significantly higher than that in fluorescence visualization-retained
      (fluorescence visualization-negative) samples. There was a constant trend of
      decreasing NPS of margin samples from non-adjacent-fluorescence visualization
      margins to adjacent-fluorescence visualization margins. CONCLUSION: Our results
      suggested that using fluorescence visualization to guide surgery has the
      potential to spare more normal tissue at surgical margins.

PMID- 29451954
TI  - 5-HT7 Receptor Antagonists with an Unprecedented Selectivity Profile.
AB  - Selective leads: In this study, we generated a new series of serotonin 5-HT7
      receptor antagonists. Their synthesis, structure-activity relationships, and
      selectivity profiles are reported. This series includes 5-HT7 antagonists with
      unprecedented high selectivity for the 5-HT7 receptor, setting the stage for lead
      optimization of drugs acting on a range of neurological targets.

PMID- 29451955
TI  - Relationship between subchondral bone microstructure and articular cartilage in
      the osteoarthritic knee using 3T MRI.
AB  - BACKGROUND: The importance of subchondral bone in the pathogenesis of
      osteoarthritis (OA) has drawn interest. PURPOSE: To investigate subregional
      trabecular bone microstructural features and to determine the relationship
      between cartilage and trabecular bone in the osteoarthritic human knee. STUDY
      TYPE: Prospective study. SUBJECTS: In all, 92 knees were enrolled and divided
      into three groups: without OA, mild OA, and severe OA. SEQUENCE: A sagittal 3D
      balanced fast field echo (3D B-FFE) sequence and FatSat 3D fast field echo (3D
      FFE) sequence at 3T MRI. ASSESSMENT: The trabecular bone in 12 sites of the knee
      joint was evaluated using digital topological analysis, and the cartilage
      thickness in four sites was calculated. STATISTICAL TEST: Trabecular bone and
      cartilage parameters between groups were compared using analysis of variance
      (ANOVA) with Bonferroni adjustment, and their correlations were analyzed using
      Pearson's correlation coefficient. RESULTS: Within both femoral condyles, the
      trabecular bone structure deteriorated in mild OA, showing a lower bone volume
      fraction (BVF) (0.15 to 0.12, P < 0.05), higher erosion index (EI) (2.25 to 2.28,
      P < 0.01), and a lower plate-to-rod ratio (SCR) (6.22 to 5.96, P < 0.05). Within
      medial and lateral tibia, deterioration in the trabecular bone was also observed,
      demonstrating a lower BVF (0.15 to 0.12 P < 0.05) and a higher EI (2.25 to 2.61,
      P < 0.05). Cartilage attrition mainly occurred in the medial joint. Extensive
      correlations were found between the medial cartilage thickness and subregional
      trabecular parameters. There was mainly a positive correlation with both femoral
      BVFs (r > 0.3, P < 0.05), and a negative correlation with the tibia SCR (r < 
      0.2, P < 0.05). DATA CONCLUSION: In the early stage of OA, trabecular bone
      osteoporotic changes were observed in both femoral condyles and the tibia. Based
      on a strong correlation with the medial cartilage thickness, the trabecular
      structural topological analysis may be useful for elucidating OA onset and
      progression. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson.
      Imaging 2018.

PMID- 29451956
TI  - Posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) as per ICD-11
      proposals: A population study in Israel.
AB  - BACKGROUND: The current study sought to advance the existing literature by
      providing the first assessment of the factorial and discriminant validity of the
      ICD-11 proposals for posttraumatic stress disorder (PTSD) and complex PTSD
      (CPTSD) in a nationwide level. METHODS: A nationally representative sample from
      Israel (n = 1,003) using a disorder-specific measure (ITQ; International Trauma
      Questionnaire) in order to assess PTSD and CPTSD along with the Life Events
      Checklist and the World Health Organization Well-Being Index. RESULTS: Estimated
      prevalence rates of PTSD and CPTSD were 9.0 and 2.6%, respectively. The
      structural analyses indicated that PTSD and disturbances in self-organization
      symptom clusters were multidimensional, but not necessarily hierarchical, in
      nature and there were distinct classes that were consistent with PTSD and CPTSD.
      CONCLUSIONS: These results partially support the factorial validity and strongly
      support the discriminant validity of the ICD-11 proposals for PTSD and CPTSD in a
      nationally representative sample using a disorder-specific measure; findings also
      supported the international applicability of these diagnoses. Further research is
      required to determine the prevalence rates of PTSD and CPTSD in national
      representative samples across different countries and explore the predictive
      utility of different types of traumatic life events on PTSD and CPTSD.

PMID- 29451957
TI  - Outcome of childhood anorexia nervosa-The results of a five- to ten-year follow
      up study.
AB  - OBJECTIVE: Although admissions of children with anorexia nervosa (AN) are
      increasing, there remains a dearth of up-to-date knowledge of the course and
      outcome of early-onset AN. The aim of the present study was to investigate the
      outcomes of patients with AN onset before the age of 14. METHOD: Sixty-eight
      consecutive former patients who met the DSM-IV criteria for AN and who had been
      treated at one of three German university hospitals were asked to participate in
      a follow-up study. Body mass index, body height, outcome of the eating disorder
      (ED), psychiatric morbidity, and health related quality of life (HRQoL) were
      assessed through a personal examination after an average time span of 7.5 years
      (range: 4.5-11.5 years) after admission. RESULTS: One patient had died. Fifty-two
      subjects with a mean age of 12.5 (SD 1.0) years at admission and of 20.2 (SD 2.0)
      years at follow-up agreed to participate in the follow-up assessment, aggregating
      to 77.9% of the original sample. Approximately 41% of the participants had a good
      outcome, while 35% and 24% had intermediate and poor outcomes, respectively.
      Twenty-eight percent of the sample met the DSM-IV criteria for a current non-ED
      psychiatric disorder, and 64% met the criteria for a past non-ED psychiatric
      disorder. Mental HRQoL and ED-specific psychopathology was strongly associated
      with the outcome of AN. Average body height was below the normal range. A higher
      weight at admission was the only significant positive indicator of outcome.
      DISCUSSION: Childhood AN is a serious disorder with an unfavorable course in many
      patients and high rates of chronicity and psychiatric comorbidity in young
      adulthood. Early detection and intervention are urgently needed.

PMID- 29451958
TI  - Peripartum cardiomyopathy: Status 2018.
AB  - Peripartum cardiomyopathy is a rare cardiac condition, overall. However, in
      certain populations can be found frequently enough and the signs, symptoms, and
      management should be readily understood. Here we provide an updated overview of
      this topic.

PMID- 29451959
TI  - Network analysis: An innovative framework for understanding eating disorder
      psychopathology.
AB  - Network theory and analysis is an emerging approach in psychopathology research
      that has received increasing attention across fields of study. In contrast to
      medical models or latent variable approaches, network theory suggests that
      psychiatric syndromes result from systems of causal and reciprocal symptom
      relationships. Despite the promise of this approach to elucidate key mechanisms
      contributing to the development and maintenance of eating disorders (EDs), thus
      far, few applications of network analysis have been tested in ED samples. We
      first present an overview of network theory, review the existing findings in the
      ED literature, and discuss the limitations of this literature to date. In
      particular, the reliance on cross-sectional designs, use of single-item self
      reports of symptoms, and instability of results have raised concern about the
      inferences that can be made from network analyses. We outline several areas to
      address in future ED network analytic research, which include the use of
      prospective designs and adoption of multimodal assessment methods. Doing so will
      provide a clearer understanding of whether network analysis can enhance our
      current understanding of ED psychopathology and inform clinical interventions.

PMID- 29451960
TI  - Direct Measurement of Charge Regulation in Metalloprotein Electron Transfer.
AB  - Determining whether a protein regulates its net electrostatic charge during
      electron transfer (ET) will deepen our mechanistic understanding of how
      polypeptides tune rates and free energies of ET (e.g., by affecting
      reorganization energy, and/or redox potential). Charge regulation during ET has
      never been measured for proteins because few tools exist to measure the net
      charge of a folded protein in solution at different oxidation states. Herein, we
      used a niche analytical tool (protein charge ladders analyzed with capillary
      electrophoresis) to determine that the net charges of myoglobin, cytochrome c,
      and azurin change by 0.62+/-0.06, 1.19+/-0.02, and 0.51+/-0.04 units upon single
      ET. Computational analysis predicts that these fluctuations in charge arise from
      changes in the pKa  values of multiple non-coordinating residues (predominantly
      histidine) that involve between 0.42-0.90 eV. These results suggest that
      ionizable residues can tune the reactivity of redox centers by regulating the net
      charge of the entire protein-cofactor-solvent complex.

PMID- 29451961
TI  - Patterns of care and outcomes of adjuvant therapy for high-risk head and neck
      cancer after surgery.
AB  - BACKGROUND: Postoperative chemoradiotherapy (CRT) is considered standard of care
      in patients with locally advanced head and neck cancer with positive margins
      and/or extracapsular extension (ECE). METHODS: The National Cancer Data Base
      (NCDB) was queried to identify patients with squamous cell carcinoma of the head
      and neck with stages III to IVB disease or with positive margins and/or ECE
      diagnosed between 2004 and 2012 receiving postoperative radiotherapy (RT). Using
      univariable and multivariable logistic and Cox regression, we assessed for
      predictors of CRT use and covariables impacting overall survival (OS), including
      in a propensity-matched subset. RESULTS: Of 12 224 patients, 67.1% with positive
      margins and/or ECE received CRT as well as 54.0% without positive margins and/or
      ECE. The 5-year OS was 61.6% for RT alone versus 67.4% for CRT. In the propensity
      matched cohort, OS benefit persisted with CRT, including in a subset with
      positive margins and/or ECE but not without. CONCLUSION: Postoperative CRT seems
      underutilized with positive margins and/or ECE and overutilized without positive
      margins and/or ECE. The CRT was associated with improved OS but the benefit
      persisted only in the subset with positive margins and/or ECE.

PMID- 29451962
TI  - Nucleopeptide Assemblies Selectively Sequester ATP in Cancer Cells to Increase
      the Efficacy of Doxorubicin.
AB  - Herein, we report that assemblies of nucleopeptides selectively sequester ATP in
      complex conditions (for example, serum and cytosol). We developed assemblies of
      nucleopeptides that selectively sequester ATP over ADP. Counteracting enzymes
      interconvert ATP and ADP to modulate the nanostructures formed by the
      nucleopeptides and the nucleotides. The nucleopeptides, sequestering ATP
      effectively in cells, slow down efflux pumps in multidrug-resistant cancer cells,
      thus boosting the efficacy of doxorubicin, an anticancer drug. Investigation of
      11 nucleopeptides (including d- and l-enantiomers) yields five more
      nucleopeptides that differentiate ATP and ADP through either precipitation or
      gelation. As the first example of assemblies of nucleopeptides that interact with
      ATP and disrupt intracellular ATP dynamics, this work illustrates the use of
      supramolecular assemblies to interact with small and essential biological
      molecules for controlling cell behavior.

PMID- 29451963
TI  - Aortic valve stenosis and aortic diameters determine the extent of increased wall
      shear stress in bicuspid aortic valve disease.
AB  - BACKGROUND: Use of 4-dimensional flow magnetic resonance imaging (4D-flow MRI)
      derived wall shear stress (WSS) heat maps enables identification of regions in
      the ascending aorta with increased WSS. These regions are subject to
      dysregulation of the extracellular matrix and elastic fiber degeneration, which
      is associated with aortic dilatation and dissection. PURPOSE: To evaluate the
      effect of the presence of aortic valve stenosis and the aortic diameter on the
      peak WSS and surface area of increased WSS in the ascending aorta. STUDY TYPE:
      Prospective. SUBJECTS: In all, 48 bicuspid aortic valve (BAV) patients (38.1 +/-
      12.4 years) and 25 age- and gender-matched healthy individuals. FIELD
      STRENGTH/SEQUENCE: Time-resolved 3D phase contrast MRI with three-directional
      velocity encoding at 3.0T. ASSESSMENT: Peak systolic velocity, WSS, and aortic
      diameters were assessed in the ascending aorta and 3D heat maps were used to
      identify regions with elevated WSS. STATISTICAL TESTS: Comparisons between groups
      were performed by t-tests. Correlations were investigated by univariate and
      multivariate regression analysis. RESULTS: Elevated WSS was present in 15 +/- 11%
      (range; 1-35%) of the surface area of the ascending aorta of BAV patients with
      aortic valve stenosis (AS) (n = 10) and in 6 +/- 8% (range; 0-31%) of the
      ascending aorta of BAV patients without AS (P = 0.005). The mid-ascending aortic
      diameter negatively correlated with the peak ascending aortic WSS (R = -0.413, P
      = 0.004) and the surface area of elevated WSS (R = -0.419, P = 0.003).
      Multivariate linear regression analysis yielded that the height of peak WSS and
      the amount of elevated WSS depended individually on the presence of aortic valve
      stenosis and the diameter of the ascending aorta. DATA CONCLUSION: The extent of
      increased WSS in the ascending aorta of BAV patients depends on the presence of
      aortic valve stenosis and aortic dilatation and is most pronounced in the
      presence of AS and a nondilated ascending aorta. LEVEL OF EVIDENCE: 2 Technical
      Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2018;48:522-530.

PMID- 29451964
TI  - A long-term comparative prospective study between reinnervation and injection
      laryngoplasty.
AB  - OBJECTIVES: This study compared and assessed long-term voice outcomes when
      thyroidectomy-related unilateral vocal fold paralysis (VFP) was managed using
      injection laryngoplasty (IL) and recurrent laryngeal nerve reinnervation (RLNR).
      STUDY DESIGN: Prospective clinical study. METHODS: A prospective clinical trial
      was performed from March 2005 to January 2016 at Soonchunhyang University Bucheon
      Hospital (Bucheon, South Korea). Nineteen patients who underwent ansa cervicalis
      to RLNR or direct reinnervation, and 43 patients who underwent IL to treat
      thyroidectomy-related unilateral VFP, were enrolled. RESULTS: All voice
      parameters exhibited statistically significant improvement 12 months post-IL,
      which persisted for 24 and 36 months (P < 0.05). However, at 36 months post-IL,
      some voice parameters had deteriorated relative to the values at 24 months post
      IL. After RLNR, all voice parameters exhibited statistically significant
      improvement after 12 months, and the improvements remained stable until 36 months
      postsurgery without deterioration of voice parameters (P < 0.05). At 36 months,
      RLNR provided better voice results than IL (P < 0.05). CONCLUSION: Both RLNR and
      IL yielded statistically significant voice improvements at 36 months
      postoperatively. However, after 36 months, RLNR provided better results than IL.
      LEVEL OF EVIDENCE: 3. Laryngoscope, 1893-1897, 2018.

PMID- 29451965
TI  - Pazopanib effective for bevacizumab-unresponsive epistaxis in hereditary
      hemorrhagic telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) most commonly manifests with nasal
      mucosal telangiectasias, and vascular endothelial growth factor (VEGF) plays a
      significant role in this angiodysplasia. We describe a patient with HHT with
      epistaxis recalcitrant to several endonasal procedures and six cycles of
      intravenous bevacizumab, for which he was dependent on iron infusions and packed
      red blood cells transfusions. He then started pazopanib at 100 mg with dramatic
      improvements in epistaxis and normalization of hemoglobin and iron levels,
      without replenishment needs for 12 months. This is the first report on the
      efficacy of pazopanib with high selectivity for abrogating VEGF receptor-2
      signaling in HHT, and needs to be explored further. Laryngoscope, 128:2234-2236,
      2018.

PMID- 29451966
TI  - How Can We Disseminate Nursing Science More Effectively?

PMID- 29451968
TI  - Establishment of Mimosa biuncifera (Fabaceae) inoculated with arbuscular
      mycorrhizal fungi in greenhouse and field drought conditions.
AB  - Mexico is dominated by arid or semi-arid ecosystems, predominantly characterized
      as xeric shrublands.These areas are frequently deteriorated due to agriculture or
      over-grazing by livestock (sheep and goats).The vegetation type mainly consists
      of thorny plant species, and among these, the dominant one in overgrazedareas is
      catclaw (Mimosa biuncifera). This is a nurse plant that facilitates establishment
      of other vegetation andpromotes plant succession. Catclaw plants form a
      mutualistic association with arbuscular mycorrhizal fungi(AMF), which improves
      uptake of nutrients and water. The objective of this study was to determine the
      effectof inoculating catclaw plants with native AMF and starting their growth
      under a low water availability treatmentin a greenhouse, and later transplanting
      them to field conditions of drought and deterioration. Field plants wereevaluated
      according to their survivorship and growth. The seeds of catclaw plants and soil
      with AMF sporeswere collected in the Mezquital Valley of Hidalgo State, in
      Central Mexico. Seedlings were grown in individualpots in a greenhouse. The
      experimental design consisted of two levels of pot irrigation, wet (W) and dry
      (D),as well as the presence (M+) or absence (M-) of AMF inoculum, with 20
      replicates for each treatment. The followingplant parameters were recorded every
      week: height, number of leaves and pinnae, and mean diameterof coverage. After 20
      weeks in the greenhouse, determination was made of fresh and dry biomass,
      relativegrowth rate (RGR), root/shoot ratio, real evapotranspiration (RET), water
      use efficiency (WUE), and percentageof mycorrhizal colonization. The remaining
      plants growing under the dry treatment (M+ and M-) were thentransplanted to a
      semi-arid locality in the Mezquital Valley. During one year, monthly records were
      kept of theirheight, number of leaves, mean diameter of coverage and survival.
      Results showed that compared to greenhouseplants under other treatments, those
      under the wet mycorrhizal (WM+) treatment were taller, had more pinnae,and were
      characterized by greater coverage, faster RGR, and greater fresh and dry biomass.
      Moreover, inoculatedplants (WM+ and DM+) showed higher WUE than those
      uninoculated (WM- and DM-, respectively).After one year in field conditions,
      there was a higher survival rate for previously inoculated versus
      uninoculatedplants. Hence, mycorrhization of M. biuncifera with native AMF
      inoculum increased plant efficiency in biomassproduction, thus favoring
      establishment and survival in field conditions. We concluded that inoculation
      ofcatclaw plants is recommendable for revegetation programs in deteriorated semi
      arid zones.

PMID- 29451969
TI  - The inhibitory effect of a non-yessotoxin-producing dinoflagellate, Lingulodinium
      polyedrum (Stein) Dodge, towards Vibrio vulnificus and Staphylococcus aureus.
AB  - The increased bacterial resistance to antibiotics has caused global concern,
      prompting the search fornew compounds. Because of their abundance and diversity,
      marine phytoplankton are an important potentialsource of such compounds. Research
      on dinoflagellates has led to the discovery of inhibitors of bacterial growth.The
      marine dinoflagellate Lingulodinium polyedrum blooms in different regions of the
      world, including Mexico,and is also known to regulate the growth of other species
      in coastal waters. Here, we investigated the taxonomyof this dinoflagellate and
      characterized the ability of its extracts to inhibit the growth of two bacteria
      of medicalimportance (Vibrio vulnificus and Staphylococcus aureus). Taxonomic
      characterization was performed byPCR and gene amplification of ITS, and confirmed
      that the species isolated off the Pacific coast of Mexico wasL. polyedrum. To
      prove the inhibitory effect of L. polyedrum extracts, cultures were harvested by
      centrifugation.Pellets from three cellular abundances were extracted with water,
      methanol, hexane and chloroform. Theexperiments on V. vulnificus showed a high
      growth inhibition for the four extracts, ranging from 77 to 98 %.Surprisingly,
      the growth inhibition was lower when the extracts originated from a higher L.
      polyedrum cell abundance,ranging from 0 to 34 %. For S. aureus, the growth
      inhibition was also high, but not statistically differentfor all extracts and
      cell abundances, ranging from 62 to 99 %. This study obtained promising results
      for futurepharmacological applications. Our Mexican strain of L. polyedrum did
      not produce any detectable yessotoxins.

PMID- 29451967
TI  - Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis
      of randomized placebo-controlled trials.
AB  - The purpose of this study was to examine the efficacy of cognitive behavioral
      therapy (CBT) for anxiety-related disorders based on randomized placebo
      controlled trials. We included 41 studies that randomly assigned patients (N =
      2,843) with acute stress disorder, generalized anxiety disorder (GAD), obsessive
      compulsive disorder (OCD), panic disorder (PD), posttraumatic stress disorder
      (PTSD), or social anxiety disorder (SAD) to CBT or a psychological or pill
      placebo condition. Findings demonstrated moderate placebo-controlled effects of
      CBT on target disorder symptoms (Hedges' g = 0.56), and small to moderate effects
      on other anxiety symptoms (Hedges' g = 0.38), depression (Hedges' g = 0.31), and
      quality of life (Hedges' g = 0.30). Response rates in CBT compared to placebo
      were associated with an odds ratio of 2.97. Effects on the target disorder were
      significantly stronger for completer samples than intent-to-treat samples, and
      for individuals compared to group CBT in SAD and PTSD studies. Large effect sizes
      were found for OCD, GAD, and acute stress disorder, and small to moderate effect
      sizes were found for PTSD, SAD, and PD. In PTSD studies, dropout rates were
      greater in CBT (29.0%) compared to placebo (17.2%), but no difference in dropout
      was found across other disorders. Interventions primarily using exposure
      strategies had larger effect sizes than those using cognitive or cognitive and
      behavioral techniques, though this difference did not reach significance.
      Findings demonstrate that CBT is a moderately efficacious treatment for anxiety
      disorders when compared to placebo. More effective treatments are especially
      needed for PTSD, SAD, and PD.

PMID- 29451970
TI  - [Ecological ensembles and assemblages - a reply to Monge-Najera].
AB  - Critical evaluation of terminology use in ecology is important to avoid using
      jargon that helps little to facilitate communication. Here we reply to Monge
      Najera's comment on the use of the terms ensemble and assemblage, we argue for
      the use of the words ensamble and ensamblaje in Spanish. In addition, both terms
      have a proper place in ecology and we provide a case for their use in proper
      ecological context.

PMID- 29451971
TI  - [Evaluation of the growth of Callinectes sapidus (Decapoda: Portunidae) by the
      use of lengthbased methods based on size in Tamaulipas, Mexico].
AB  - The capture blue crab (Callinectes sapidus) is one of the major fisheries of the
      state of Tamaulipas, Mexico; both in volume and selling price, as well as
      employment generation, but there is little information on its biological
      characteristics. The aim of this study was to evaluate the growth parameters of
      the blue crab, establishing the most appropriate method. We estimated the length
      frequency of 17 814 crabs from commercial catch of thirteen locations, including
      four coastal lagoons. The lagoons were El Barril, Madre, Morales and San Andres
      from Tamaulipas, State. Growth parameters were evaluated using indirect methods
      ELEFAN, PROJMAT and SLCA in combination with the jackknife technique to establish
      the uncertainty of estimates inherent in each method. The growth parameters
      Linfinity and k were consolidated for purposes of comparison with the growth
      index phi prime (Phi'). With a mode of 110 mm, the interval carapace length
      varied between 60 and 205 mm. The values of the growth parameters varied
      according to the method used. Using SLCA, Linfinity varied between 259 and 260 mm
      and k ranged between 0.749 and 0.750 /year; with PROJMAT, Linfinity recorded
      values between 205 and 260 mm, k fluctuated between 0.550 and 0.740/year, and
      with ELEFAN, Linfinity ranged between 156 and 215 mm and k varied between 0.479
      and 0.848/year. Estimates by jackknife detected no variability in Phi' between
      locations and significant differences between methods. The ranges of values of
      Phi' and PROJMAT estimated SLCA (4.70 to 4.71 and 4.66 to 4.70, respectively)
      were in the range reported in the literature (4.201-4.798), while lower values
      ELEFAN contributed significantly (3.87 to 4.27). The SLCA and PROJMAT methods in
      combination with the jackknife technique, proved to be the most suitable to
      estimate the growth parameters of C. sapidus.

PMID- 29451972
TI  - Understanding trophic relationships among Caribbean sea urchins.
AB  - The species Echinometra lucunter, Echinometra viridis, Lytechinus variegatus,
      Tripneustes ventricosus,and Diadema antillarum are the most common sea urchins of
      littoral habitats in the Caribbean. T.ventricosus and L. variegatus are
      associated with seagrass beds, while the other three species usually
      inhabithardground substrates. Food preferences of these species are well
      documented and they are commonly acceptedas being primarily herbivorous
      omnivorous; nevertheless, few of them have previously been characterized
      isotopically.We used this approach for assessing the isotopic characterization of
      five echinoids. We established thetrophic position of two groups of co-occurring
      species and quantified the contribution of food resources in thediet of
      Echinometra lucunter, considered the most common sea urchin in the Caribbean
      region. The species T.ventricosus and D. antillarum showed the highest values of
      delta15N. Sea urchins exhibited similar values of delta13Cvarying from -11.6 +/-
      0.63 to -10.4 +/- 0.99%. The echinoid E. lucunter displayed the lowest values of
      carbon,from -15.40 +/- 0.76%. Significant differences among species were found
      for delta15N and delta13C. Seaweed communitiesexhibited no differences among
      sites for overall delta15N (F= 1.300, df= 3, p= 0.301), but we found
      spatialdifferences for delta13C (F= 7.410, df= 3, p= 0.001). The ellipse-based
      metrics of niche width analysis found thatthe hardground biotope species (D.
      antillarum, E. lucunter, and E. viridis) did not overlap each other.
      Similarresults were obtained for the co-occurring species of the seagrass
      biotope; however, the distance between thesespecies was closer than that of the
      hardground biotope species. The Bayesian mixing models run for E. lucunterat all
      four localities found differences in food resources contribution. The algae D.
      menstrualis, C. crassa andB. triquetrum dominated in CGD; whereas C. nitens,
      Gracilaria spp., and D. caribaea represented the maincontributor algae to the
      diet of E. lucunter at LQY. In Culebra Island, no dominance of any particular
      algae wasdetected in TMD, where six of the eight species exhibited a similar
      contribution. Similarities in delta15N between D.antillarum and T. ventricosus
      may hint towards a similar trophic level for these species, although T.
      ventricosusis widely accepted as an omnivore, while D. antillarum is considered a
      generalist herbivore. The lack of overlapamong species in the two biotopes seems
      to indicate a resource partitioning strategy to avoid niche competitionamong co
      occurring species.

PMID- 29451973
TI  - [Histochemistry of the digestive gland of the pearl oyster Pinctada imbricata
      (Pterioida: Pteriidae) during the gametogenic cycle, Venezuela].
AB  - Histochemical techniques today allow you to select areas of tissue and generate
      reliable information on the distribution of energy reserves in bivalve molluscs
      during their life cycle. The main objective of this study was to describe and
      relate the gametogenic cycle with the availability of energy reserves and the
      environmental parameters. For this, we sampled and examined the gonads and
      digestive glands (DG) of 15 individuals collected monthly during April 2012 and
      February 2013. We processed and analyzed the samples by standard histological and
      histochemical light microscopy techniques. Our results showed that for the
      gametogenic cycle, the monthly proportion of mature organisms was higher for
      males, between August (40 %) and November (53 %), while the females tend to have
      a shorter synchronized cycle and release of gametes in September (67 %) and
      October (60 %). The intense spawning periods in both sexes was the same (October
      to January). Between the periods April-August 2012 and January-February 2013, we
      observed the highest values of IGl and glucide index (instead, a decrease was
      observed in September, reaching minimumvalues during the period October
      December). Besides, the maximum values of IL, lipid index, were observed in April
      2012 and February-2013, with an intermediate value in August-2013. The results
      indicated that the reserves of the GD have a pattern of mobilization inversely
      related to the proliferation of gametes in both sexes; this was directly linked
      to the availability of nutrients such as chlorophyll a and the organic seston.

PMID- 29451974
TI  - [Regenerative morphological traits in a woody species community in Tumbesian
      tropical dry forest].
AB  - The study of functional morphological traits enables us to know fundamental
      aspects of the dynamicsof plant communities in local and global habitats.
      Regenerative morphological traits play an important role indefining plant history
      and ecological behavior. Seed and fruit characteristics determine to a large
      extent the patternsfor dispersal, germination, establishment and seedling
      recruitment a given species exhibits on its naturalhabitat. Despite their
      prominent role, seed and fruit traits have been poorly studied at the community
      level ofwoody plant species in neo-tropical dry forests. In the present study we
      aimed at i) evaluate the functional roleof morphological traits of seeds, fruits
      and embryo in woody plant species; ii) determine which are the
      morphologicalpatterns present in seeds collected from the community of woody
      species that occur in neo-tropicaldry forests; and iii) compare woody plant
      species seed mass values comparatively between neo-tropical dry andtropical
      forests. To do so, mature seeds were collected from 79 plant species that occur
      in the Tumbesian forest ofSouthwest Ecuador. The studied species included the 42
      and 37 most representative tree and shrubbery species ofthe Tumbesian forest
      respectively. A total of 18 morphological traits (seven quantitative and 11
      qualitative) weremeasured and evaluated in the seeds, fruits and embryos of the
      selected species, and we compared the seeds masswith other forest types. Our
      results showed a huge heterogeneity among traits values in the studied species.
      Seedmass, volume and number were the traits that vary the most at the community
      level, i.e. seed length ranged from1.3 to 39 mm, and seed width from 0.6 to 25
      mm. Only six embryo types were found among the 79 plant species.In 40 % of the
      cases, fully developed inverted embryos with large and thick cotyledons to store
      considerableamount of nutrients were recorded. We concluded that highly variable
      and functionally complementary morphologicaltraits occur among the studied woody
      plants of the Tumbesian dry forest. The latter favors a plethora ofbehavioral
      mechanisms to coexist among woody species of the dry forest in response to the
      environmental stressthat is typical of arid areas.

PMID- 29451975
TI  - Using a jumping spider fauna inventory (Araneae: Salticidae) as an indicator of
      their taxonomic diversity in Misiones, Argentina.
AB  - Faunistic studies, with a taxonomically complete inventory of species, provide an
      important sourceof quantitative compiled information for several and specific
      regions. This information can be used in diversityanalysis and has great
      potential in setting conservation priorities. In this study, I used the
      relatively well knownsalticid spider fauna of Misiones to generate Clarke &
      Warwick taxonomic diversity indices. For this, informationof three ecoregional
      salticid diversities was obtained and analyzed between Upper Parana Atlantic
      Forest(UPAF), Araucaria Moist Forest (AMF), and Southern Cone Mesopotamian
      Savanna (SCMS). Results showeddifferences between the three ecoregions of the
      province, mainly Southern savannas regarding the forests ofNorthern Misiones.
      Most species were registered in UPAF followed by AMF, however the alpha-taxonomic
      diversityof salticids was higher in SCMS than in UPAF and AMF. The beta-taxonomic
      diversity showed that the proportionsof shared species between SCMS and UPAF (or
      and AMF) were the lowest. The high taxonomic dissimilarityamong ecoregions is an
      indication that the three assemblages are distant, showing a variation in their
      vegetationhabitat and/or bioclimatic characteristics as a possible reason. The
      need to expand with new samples in subsampledor underexplored areas of Misiones
      remains essential, however this study contributes to informationabout
      biodiversity levels of salticid fauna in three ecoregions of Northeast Argentina,
      and will provide referencedata for future studies for management plans.

PMID- 29451976
TI  - Early harvest increases post-harvest physiological quality of Araucaria
      angustifolia (Araucariaceae) seeds.
AB  - Araucaria angustifolia is a conifer native to Brazil and is an endangered
      species. Since this speciesseeds have a short period of viability, its
      vulnerability is higher. Thus the aim of this study was to evaluate
      thephysiological quality of A. angustifolia seeds during the development and post
      storage periods. For this, conesof A. angustifolia were collected from a natural
      population in Curitibanos, Santa Catarina, Brazil, in March,April, May and June
      2012. The collected seeds were classified into developmental stages of
      cotyledonary, I, IIand III according to the month of collection; a total of 10
      cones were collected for each stage. Seeds were storedin a refrigerator for 60
      and 120 days, and were submitted to a chamber germination test (25  degrees C
      photoperiod 12h). Additionally, seeds were tested for moisture content (105 
      degrees C for 24 hours), tetrazolium (0.1 % for 1 hour)and vigor (electric
      conductivity [75 mL distilled water at 25  degrees C], germination speed index,
      and shoot and rootlength). Our results showed that during seed development,
      moisture content decreased from the cotyledonarystage (66.54 %) to stage III
      (49.69 %), and vigor increased in the last stage. During storage, moisture
      contentat cotyledonary stage and stage I was stable. On the other hand, stored
      seeds exhibited a decrease in moisturecontent after 120 days at stages II and
      III. Physiological quality at the cotyledonary stage resulted in an
      increasedgermination rate of 86 % and 93 % after 60 and 120 days of storage,
      respectively; unlike stages II and IIIexhibited a decrease in seed viability and
      vigor after storage. Electrical conductivity was higher for fresh seedsat the
      cotyledonary stage, than for those stored for 60 and 120 days. However, in other
      stages, released leachatecontent after 120 days of storage, increased with the
      advance of the collection period. Germination speed indexand shoot and root
      lengths after storage were highest for seeds at the cotyledonary stage and stage
      I; unlikestages II and III which had short root and shoot lengths during storage.
      Thus, the maintenance of seed moisturecontent during storage was variable and
      dependent on the period of collection. Furthermore, the physiologicalquality
      differed among earlier and later stages. Early collection favored seed
      physiological quality, and may bea strategy for better conservation of A.
      angustifolia seeds.

PMID- 29451977
TI  - [Tree above-ground biomass allometries for carbon stocks estimation in the
      Caribbean mangroves in Colombia].
AB  - The distribution of carbon in "Blue Carbon" ecosystems such as mangroves is
      little known,when compared with the highly known terrestrial forests, despite its
      particular and recognized high productivityand carbon storage capacity. The
      objective of this study was to analyze the above ground biomass (AGB) ofthe
      species Rhizophora mangle and Avicennia germinans from the Marine Protected Area
      of Distrito de ManejoIntegrado (DMI), Cispata-Tinajones-La Balsa, Caribbean
      Colombian coast. With official authorization, weharvested and studied 30
      individuals of each species, and built allometric models in order to estimate
      AGB.Our AGB results indicated that the studied mangrove forests of the DMI
      Colombian Caribbean was of 129.69+/- 20.24 Mg/ha, equivalent to 64.85 +/- 10.12
      MgC/ha. The DMI has an area of 8 570.9 ha in mangrove forests,and we estimated
      that the total carbon potential stored was about 555 795.93 Mg C. The equations
      generated inthis study can be considered as an alternative for the assessment of
      carbon stocks in AGB of mangrove forestsin Colombia; as other available AGB
      allometric models do not discriminate mangrove forests, despite beingparticular
      ecosystems. They can be used for analysis at a more detailed scale and are
      considered useful to determinethe carbon storage potential of mangrove forests,
      as a country alternative to support forest conservation andemission reduction
      strategies. In general, the potential of carbon storage from Colombian Caribbean
      mangroveforests is important and could promote the country leadership of the
      "blue carbon" stored.

PMID- 29451978
TI  - Bloom of Trichodesmium (Oscillatoriales, Phormidiaceae) and seasonality of
      potentially harmful phytoplankton in San Pedro Bay, Leyte, Philippines.
AB  - Since 1983, San Pedro Bay in the Philippines had been reported to be the site of
      episodic Pyrodinium bahamense var. compressum blooms that caused paralytic
      shellfish poisoning in its nearby coastal communities. This bay is also subjected
      to numerous storms; the strongest was super typhoon Haiyan in November 8, 2013.
      For the first time, the seasonal dynamics of potentially toxic and harmful
      phytoplankton in this bay is elucidated. This is also the first record of a bloom
      of the cyanobacteria, Trichodesmium erythraeum that reached 70 000 colonies/L in
      April 2013 in this area. There were other 19 potentially toxic and harmful
      phytoplankton encountered during the sampling period. These consisted of a
      haptophyte, Phaeocystis globosa, the diatom Pseudo-nitzschia and 17
      dinoflagellates. Seven of these harmful algae had densities high enough to be
      traced through time. Normally, diatoms abound during the dry season. But Pseudo
      nitzschia increased in abundance during the wet season of 2012 and 2013. The
      dinoflagellates and Phaeocystis globosa behaved as expected and exhibited a
      relative increase in cell density during the rainy season of both years too. High
      nutrient availability during this season must have influenced the behavior of the
      phytoplankton despite differences in temperature and light intensity among
      seasons. Other notable but rare harmful species found only in plankton net tows
      during the study were Pyrodinium bahamense var. compressum, Alexandrium
      tamiyavanichii, Cochlodinium polykrikoides, and Noctiluca scintillans.

PMID- 29451979
TI  - Neat Protein-Polymer Surfactant Bioconjugates as Universal Solvents.
AB  - Solvents, particularly those having low volatility, are of great interest for the
      biocatalytic synthesis of utility chemicals and fuels. We show novel and
      universal solvent-like properties of a neat and water-less polymer surfactant
      bovine serum albumin (BSA) conjugated material (WL-PS pBSA). This highly viscous,
      nonvolatile material behaves as a liquid above its solid-liquid transition
      temperature (~25-27  degrees C) and can be used as a solvent for variety of
      completely dry solutes of different sizes and surface chemistries. We show using
      a combination of optical microscopy and steady -state and time-resolved
      fluorescence spectroscopy that dry and powdered dyes (hydrophobic Coumarin 153
      (C153)), enzymes (alpha-chymotrypsin (alpha-Chy)), or even 1 MUm microparticles
      (diffusion coefficient ca. three orders slower than C153), can be solubilized and
      completely dispersed in the WL-PS pBSA solvent above 25  degrees C. While C153,
      irrespective of its mode of addition to WL-PS pBSA, binds similarly to BSA, alpha
      Chy can be stabilized and activated to perform its hydrolysis function, even at
      100  degrees C. This work therefore provides insights into the form of universal
      solvent characteristic property for this new class of nonaqueous, nonvolatile,
      biodegradable protein-polymer surfactant-based conjugated materials and suggests
      potential new avenues that can have a huge impact on biocatalysis,
      bionanotechnology, drug delivery, and other applications.

PMID- 29451980
TI  - Nanocarrier Composed of Magnetite Core Coated with Three Polymeric Shells
      Mediates LCS-1 Delivery for Synthetic Lethal Therapy of BLM-Defective Colorectal
      Cancer Cells.
AB  - Synthetic lethality is a molecular-targeted therapy for selective killing of
      cancer cells. We exploited a lethal interaction between superoxide dismutase 1
      inhibition and Bloom syndrome gene product (BLM) defect for the treatment of
      colorectal cancer (CRC) cells (HCT 116) with a customized lung cancer screen-1
      loaded nanocarrier (LCS-1-NC). The drug LCS-1 has poor aqueous solubility. To
      overcome its limitations, a customized NC, composed of a magnetite core coated
      with three polymeric shells, namely, aminocellulose (AC), branched
      poly(amidoamine), and paraben-PEG, was developed for encapsulating LCS-1.
      Encapsulation efficiency and drug loading were found to be 74% and 8.2%,
      respectively. LCS-1-NC exhibited sustained release, with ~85% of drug release in
      24 h. Blank NC (0.5 mg/mL) exhibited cytocompatibility toward normal cells,
      mainly due to the AC layer. LCS-1-NC demonstrated high killing selectivity (104
      times) toward BLM-deficient HCT 116 cells over BLM-proficient HCT 116 cells. Due
      to enhanced efficacy of the drug using NC, the sensitivity difference for BLM
      deficient cells increased to 1.7 times in comparison to that with free LCS-1. LCS
      1-NC induced persistent DNA damage and apoptosis, which demonstrates that LCS-1
      NC effectively and preferentially killed BLM-deficient CRC cells. This is the
      first report on the development of a potential drug carrier to improve the
      therapeutic efficacy of LCS-1 for specific killing of CRC cells having BLM
      defects.

PMID- 29451981
TI  - High Performance Anion Exchange and Hydrophilic Interaction Liquid Chromatography
      Approaches for Comprehensive Mass Spectrometry-Based Characterization of the N
      Glycome of a Recombinant Human Erythropoietin.
AB  - Comprehensive characterization of the N-glycome of a therapeutic is challenging
      because glycans may harbor numerous modifications (e.g., phosphorylation,
      sulfation, sialic acids with possible O-acetylation). The current report presents
      a comparison of two chromatographic platforms for the comprehensive
      characterization of a recombinant human erythropoietin (rhEPO) N-glycome. The two
      platforms include a common workflow based on 2-AB-derivatization and hydrophilic
      interaction chromatography (HILIC) and a native N-linked glycan workflow
      employing high performance anion exchange (HPAE) chromatography. Both platforms
      were coupled to an Orbitrap mass spectrometer, and data dependent HCD
      fragmentation allowed confident structural elucidation of the glycans. Each
      platform identified glycans not revealed by the other, and both exhibited
      strengths and weaknesses. The reductive amination based HILIC workflow provided
      better throughput and sensitivity, had good isomer resolution, and revealed the
      presence of O-acetylated sialic acids. However, it exhibited poor performance
      toward phosphorylated glycans and did not reveal the presence of sulfated
      glycans. Furthermore, reductive amination introduced dehydration artifacts and
      modified the glycosylation profile in the rhEPO glycome. Conversely, HPAE
      provided unbiased charge classification (sialylation levels), improved isomer
      resolution, and revealed multiple phosphorylated and sulfated structures, but
      delivered lower throughput, had artifact peaks due to epimer formation, and loss
      of sialic acid O-acetylation. The MS2 based identification of phosphorylated and
      sulfated glycans was not possible in HILIC mode due to their poor solubility
      caused by the high acetonitrile concentrations employed at the beginning of the
      gradient. After analyzing the glycome by both approaches and determining the
      glycans present, a glycan library was created for site specific glycopeptide
      analyses. Glycopeptide analyses confirmed all the compositions annotated by the
      combined use of 2-AB- and native glycan workflows and provided site specific
      location of the glycans. These two platforms were complementary and in
      combination delivered a more thorough and comprehensive characterization of the
      rhEPO N-glycome, supporting regulatory conformance for the pharmaceutical
      industry.

PMID- 29451982
TI  - Photodissociation of the Cyclopentadienyl Radical at 248 nm.
AB  - The photodissociation of jet-cooled cyclopentadienyl radicals, c-C5H5, at 248 nm
      was studied using photofragment translational spectroscopy. Two dissociation
      channels were observed: H + C5H4 and C3H3 + C2H2. The C5H4 fragment was
      identified as ethynylallene by its ionization energy. The translational energy
      distribution determined for each channel suggests that both dissociation
      mechanisms occur via internal conversion to the ground electronic state followed
      by intramolecular vibrational redistribution and dissociation. The experimental
      branching ratio and RRKM (Rice-Ramsperger-Kassel-Marcus) calculations favor the
      formation of C3H3 + C2H2 over the H-atom loss channel. The RRKM calculations also
      support the observation of ethynylallene as the dominant C5H4 product isomer.

PMID- 29451983
TI  - Reinforcing Mucus Barrier Properties with Low Molar Mass Chitosans.
AB  - The mucus gel covers the wet epithelia that forms the inner lining of the body.
      It constitutes our first line of defense protecting the body from infections and
      other deleterious molecules. Failure of the mucus barrier can lead to the
      inflammation of the mucosa such as in inflammatory bowel diseases. Unfortunately,
      there are no effective strategies that reinforce the mucus barrier properties to
      recover or enhance its ability to protect the epithelium. Herein, we describe a
      mucus engineering approach that addresses this issue where we physically cross
      link the mucus gel with low molar mass chitosan variants to reinforce its barrier
      functions. We tested the effect of these chitosans on mucus using in-lab purified
      porcine gastric mucins, which mimic the native properties of mucus, and on mucus
      secreting HT29-MTX epithelial cell cultures. We found that the lowest molar mass
      chitosan variant (degree of polymerization of 8) diffuses deep into the mucus
      gels while physically cross-linking the mucin polymers, whereas the higher molar
      mass chitosan variants (degree of polymerization of 52 and 100) interact only
      superficially. The complexation resulted in a tighter mucin polymer mesh that
      slowed the diffusion of dextran polymers and of the cholera toxin B subunit
      protein through the mucus gels. These results uncover a new use for low molar
      mass mucoadhesive polymers such as chitosans as noncytotoxic mucosal barrier
      enhancers that could be valuable in the prevention and treatment of mucosal
      diseases.

PMID- 29451984
TI  - Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric
      Antigens.
AB  - Antigen multimerization on a nanoparticle can result in improved neutralizing
      antibody responses. A platform that has been successfully used for displaying
      antigens from a number of different viruses is ferritin, a self-assembling
      protein nanoparticle that allows the attachment of multiple copies (24 monomers
      or 8 trimers) of a single antigen. Here, we design two-component ferritin
      variants that allow the attachment of two different antigens on a single particle
      in a defined ratio and geometric pattern. The two-component ferritin was
      specifically designed for trimeric antigens, accepting four trimers per particle
      for each antigen, and was tested with antigens derived from HIV-1 envelope (Env)
      and influenza hemagglutinin (HA). Particle formation and the presence of native
      like antigen conformation were confirmed through negative-stain electron
      microscopy and antibody-antigen binding analysis. Immunizations in guinea pigs
      with two-component ferritin particles, displaying diverse Env, HA, or both
      antigens, elicited neutralizing antibody responses against the respective
      viruses. The results provide proof-of-principle for the self-assembly of a two
      component nanoparticle as a general technology for multimeric presentation of
      trimeric antigens.

PMID- 29451986
TI  - Treatment of striae distensae: An evidence-based approach.
AB  - Striae distensae (SD), otherwise known as "stretchmarks," are a common presenting
      complaint, particularly in young healthy women. SD are hypothesized to form in a
      patient when the cross-linked collagen is "overstretched" and rupture of this
      collagen matrix causes the striae. Thus, many treatments work by increasing
      collagen synthesis. This review critically appraises the evidence to date for the
      treatment of SD, including both energy-based devices and topical treatments.

PMID- 29451985
TI  - A comparison of barriers to accessing services for mental and physical health
      conditions in a sample of rural Australian adults.
AB  - INTRODUCTION: The prevalence of chronic disease, mortality and suicide rates is
      higher in rural Australia than in urban centres. Understanding rural Australians'
      barriers to accessing health services requires urgent attention. The purpose of
      this study was to compare barriers to help-seeking for physical and mental health
      issues among rural South Australian adults. METHODS: A total of 409 people from
      three rural and remote regions in South Australia completed a computer-assisted
      telephone interview. They were presented a physical or mental health scenario and
      rated the extent to which barriers would prevent them from seeking help for that
      condition. Responses ranged from 1 ('strongly disagree') to 5 ('strongly agree')
      and were averaged to form domain scores (higher scores representing stronger
      barriers to seeking support), in addition to being examined at the item level.
      RESULTS: Men reported higher barriers for the mental compared with physical
      health scenario across four domains ('need for control and self-reliance',
      'minimising the problem, resignation and normalisation', 'privacy' and 'emotional
      control'). Women reported higher barriers for the mental compared to physical
      health scenario in two domains ('need for control and self-reliance' and
      'privacy'). Both men and women endorsed many items in the mental health context
      (eg 'I don't like feeling controlled by other people', 'I wouldn't want to
      overreact to a problem that wasn't serious', 'Problems like this are part of
      life; they're just something you have to deal with', 'I'd prefer just to put up
      with it rather than dwell on my problems', 'Privacy is important to me, and I
      don't want other people to know about my problems' and 'I don't like to get
      emotional about things') but in the physical health context, barriers were
      endorsed only by men (eg 'I wouldn't want to overreact to a problem that wasn't
      serious',' I'd prefer just to put up with it rather than dwell on my problems',
      'Problems like this are part of life; they're just something you have to deal
      with', 'I like to make my own decisions and not be too influenced by others').
      CONCLUSIONS: Both rural men and rural women report more barriers to help seeking
      for mental health issues than physical health issues across a range of domains.
      There is a need to educate the current and future rural health and mental health
      workforce about these barriers and to encourage them to test evidence-based
      strategies to address them, in particular to facilitate more widespread mental
      health help-seeking in rural Australia.

PMID- 29451987
TI  - Association of adiponectin/leptin ratio with carbohydrate and lipid metabolism
      parameters in HIV-infected patients during antiretroviral therapy.
AB  - BACKGROUND: Adiponectin and leptin are adipose tissue hormones that regulate
      important lipid and glucose metabolic pathways. Our objective was to evaluate the
      interplay of these hormones described by the adiponectin/leptin ratio (ALR) in
      correlation to lipid and carbohydrate metabolism parameters in nondiabetic HIV
      infected patients during antiretroviral therapy (ART). MATERIALS AND METHODS: We
      enrolled consecutive nondiabetic patients with confirmed HIV infection,
      undergoing stable ART regimens for at least six months. Blood samples were
      collected and tested for immunological and virological parameters, adiponectin
      and leptin, fasting insulin, fasting plasma glucose, fasting triglycerides, total
      cholesterol, LDL cholesterol, and HDL cholesterol. ALR was computed for each
      patient. Resistance to insulin was assessed by calculating the Quantitative
      Insulin Sensitivity Check Index (QUICKI). RESULTS: We enrolled 87 HIV-infected
      persons, with a mean age of 31.7 years (range: 18-65), including 47 men (mean age
      = 32.8 years) and 40 women (mean age = 30.5 years). The median value of ALR was
      6.8 (interquartile range - IQR = 17.1). In male patients, ALR was inversely
      associated with the serum level of triglycerides (R = 0.285, p = 0.05), total
      cholesterol (R = 0.326, p = 0.02), and LDL cholesterol (R = 0.298, p = 0.04).
      Also for the male cohort, an increase in ALR seemed to improve insulin
      sensitivity (R = 0.323, p = 0.02) and serum HDL cholesterol (R = 0.597, p =
      0.01). None of these correlations were observed in HIV-infected women.
      CONCLUSION: Adiponectin and leptin seem to play important but different gender
      specific roles in the pathogenesis of lipid and glucose metabolism of HIV
      infected patients undergoing antiretroviral therapy. ABBREVIATIONS: ALR,
      adiponectin/leptin ratio; BMI, body mass index; LDL, low-density lipoprotein;
      HDL, high-density lipoprotein; QUICKI, Quantitative Insulin Sensitivity Check
      Index.

PMID- 29451988
TI  - Results of Nailfold Capillaroscopy in Patients with Normal-Tension Glaucoma.
AB  - : The aim of the study was to evaluate the results of nailfold
      videocapillaroscopic examination in patients with normal-tension glaucoma (NTG)
      in comparison to age-matched individuals without glaucoma and young healthy
      volunteers and to assess the relation between the results of this examination
      with clinical status in NTG group. MATERIAL AND METHODS: The studied group
      consisted of 188 patients: 80 patients with NTG and 2 control groups (58 young
      healthy and 50 age-matched volunteers). The nailfold videocapillaroscopy (NVC)
      was performed in all participants. The results of every NVC were qualified as a
      normal or abnormal pattern. In the NTG group, ophthalmic examination was
      performed and medical history regarding glaucoma, chronic general disorders, and
      vascular risk factors was recorded. RESULTS: In the NTG group, an abnormal NVC
      pattern was more common than in young controls (p = 0.0008). Microbleedings were
      present more frequently in NTG patients (p = 0.0365). Enlargement of capillaries
      (p = 0.0006) and branching capillaries (p = 0.0221) were more frequent in the NTG
      group compared to age-matched controls. Maximal intraocular pressure was higher
      in NTG patients with abnormal NVC pattern than with normal NVC (p = 0.0000). Disc
      hemorrhages were more frequently observed in patients with abnormal NVC pattern
      (p = 0.0313). Presence of paracentral scotoma was associated with abnormal NVC
      pattern (p = 0.0054). CONCLUSIONS: Abnormalities in nailfold capillaroscopy are
      more frequent in NTG patients. The results of capillaroscopic examination differ
      in NTG patients according to the profile of ocular and general risk factor.

PMID- 29451989
TI  - All done procedure by laser in free gingival graft treatment: A case series
      study.
AB  - AIM: This case series study evaluated the application of Er;Cr:YSGG laser for a
      free gingival graft procedure and the effect of low level laser therapy on post
      surgical pain and wound healing. CASES: 6 cases with mucogingival problems
      needing free gingival grafts were selected. First, the recipient site was
      anesthetized and de-epithelialization was done with a Er;Cr:YSGG laser. After
      tracing the palatal donor site with the laser, the graft was harvested. For root
      modification of the recipient tooth, conditioning of the dentin was done by the
      same laser. The inner side of graft was trimmed by the laser before suturing at
      the recipient site. After final adaptation of the grafts and suturing process,
      the recipient and donor sites were irradiated by therapeutic laser for reduction
      of post surgical complications. RESULTS: All patients reported the reduction in
      pain level after day 2 on donor and recipient site. Also, the wound healing was
      achieved after 14 days in all cases in donor site. CONCLUSION: According to high
      surface absorbance, better incision, coagulation and application on both soft and
      hard tissues, Er;Cr:YSGG laser can be safe, minimally invasive manner and useful
      for all steps of the free gingival graft procedure.

PMID- 29451990
TI  - Intellectual efficiency in children and adolescents with spina bifida
      myelomeningocele and shunted hydrocephalus.
AB  - We studied the intellectual profiles of 13 Italian children diagnosed with spina
      bifida myelomeningocele and shunted hydrocephalus (MMC HC) against a control
      group of children. The results showed that MMC HC group had lower performance in
      all subtests, four indices, and the FSIQ of the Wechsler Intelligence Scale for
      Children, forth-edition. The MMC HC group showed flat cognitive profiles between
      subtests within each index and between four core indices. However, the cognitive
      abilities that were mostly impaired seemed to be related to visual selective and
      focused attention, to visual acuity, to visuo-perceptive organization and
      visuomotor integration and to visual short-term memory.

PMID- 29451991
TI  - Exogenous ketone salts do not improve cognitive responses after a high-intensity
      exercise protocol in healthy college-aged males.
AB  - This study examined the effects of a d-beta-hydroxybutyrate (betaHB) containing
      beverage on cognitive and performance measures during a bout of repeated
      Wingates. Fifteen healthy, college-aged males (mean +/- SD; age: 23.1 +/- 2.4
      years, height: 165.4 +/- 2.0 cm, mass: 81.4 +/- 9.2 kg) volunteered for the
      present study. Trial 1 consisted of baseline measures and familiarization for the
      protocol. During trials 2 and 3, subjects reported to the laboratory, after a 10
      h fast, and ingested 11.38 g of betaHB or a placebo (PLA) beverage 30 min before
      exercise. Participants then completed a cognitive challenge (CC), consisting of a
      5-min FitLight response task while cycling. At the cessation of the test,
      participants then completed four 15-s repeated Wingates with 4 min of rest
      between, followed by another 5-min CC response task. Blood ketones, glucose, and
      lactate were measured pre-CC and post-Wingates. betaHB levels were significantly
      higher compared with PLA (0.53 vs. 0.21 mmol/L), respectively. A significant
      order effect was observed across trials 2 and 3 for total FitLight misses and
      hits, regardless of treatment. Further, there were no significant differences
      among Wingate power output between treatments, although fatigue index was higher
      in the betaHB group compared with PLA (32.3 vs. 29.4 W/s), respectively. In
      conclusion, betaHB did not improve high-intensity cycling or cognitive
      performance measures; however, these findings might be partially explained by the
      absolute dosing protocol used for betaHB in the present study as opposed to a
      relative (g/kg) dosing protocol used in previous research.

PMID- 29451992
TI  - Optical Coherence Tomography Angiography of the Peripapillary Retina in Normal
      Tension Glaucoma and Chronic Nonarteritic Anterior Ischemic Optic Neuropathy.
AB  - PURPOSE: To analyze the retinal radial peripapillary capillary (RPC) network in
      normal-tension glaucoma (NTG) and nonarteritic anterior ischemic optic neuropathy
      (NAION) eyes using optical coherence tomography angiography (OCTA). MATERIAL AND
      METHODS: Twenty-two patients with NTG, 22 patients with unilateral chronic NAION,
      and 23 age-matched controls were enrolled. Patients underwent OCTA to obtain en
      face angiograms of the peripapillary region. The main outcome measures were as
      follows: (1) the whole en face image perfusion density (WPD) and (2) the
      circumpapillary perfusion density (CPD). RESULTS: Mean +/- SD age was 66.3 +/-
      7.0 years in the NTG group, 68.1 +/- 4.3 years in the NAION group, and 63.9 +/-
      7.0 years in the control group (p > 0.05 for all the comparisons). The visual
      field mean defect (MD) was worse in patients than in controls (p < 0.0001), but
      did not differ between NTG and NAION (-9.6 +/- 2.6 dB and -8.2 +/- 2.6 dB,
      respectively). The WPD was 0.41 +/- 0.04 in the NTG group (p < 0.0001 in
      comparison with healthy subjects and NAION patients), 0.46 +/- 0.04 in the NAION
      group (p < 0.0001 in comparison with the control group), and 0.56 +/- 0.03 in the
      control group. The CPD was significantly reduced in both NTG (0.48 +/- 0.04, p <
      0.0001) and NAION eyes (0.52 +/- 0.05, p < 0.0001), after comparison to control
      eyes (0.59 +/- 0.03). Moreover, the CPD was significantly lower in NTG than in
      NAION eyes (p = 0.006). CONCLUSIONS: OCTA documented a reduction of the
      peripapillary perfusion in NTG and unilateral NAION. In presence of similar
      functional damage, the lower perfusion densities in NTG may indicate greater
      vascular alterations in chronic compared to acute ischemic optic neuropathies.

PMID- 29451994
TI  - Stroop Task-Related Brain Activity in Patients With Insomnia: Changes After
      Cognitive-Behavioral Therapy for Insomnia.
AB  - OBJECTIVE/BACKGROUND: In the present study, we compared differences in brain
      activity during the Stroop task between patients with chronic insomnia disorder
      (CID) and good sleepers (GS). Furthermore, we evaluated changes in Stroop task
      related brain activity after cognitive-behavioral therapy for insomnia (CBT-I).
      PARTICIPANTS/METHODS: The final analysis included 21 patients with CID and 25 GS.
      All participants underwent functional magnetic resonance imaging (fMRI) while
      performing the color-word Stroop task. CBT-I, consisting of 5 sessions, was
      administered to 14 patients with CID in the absence of medication. After CBT-I,
      fMRI was repeated in the patients with CID while performing the same task. Sleep
      related questionnaires and sleep variables from a sleep diary were also obtained
      before and after CBT-I. RESULTS: No significant differences in behavioral
      performance in the Stroop task or task-related brain activation were observed
      between the CID and GS groups. No changes in behavioral performance or brain
      activity were found after CBT-I. However, clinical improvement in the Insomnia
      Severity Index (ISI) score was significantly associated with changes in the
      Stroop task-related regional blood oxygen level-dependent signals in the left
      supramarginal gyrus. CONCLUSIONS: Our findings suggest that cognitive impairment
      in patients with CID was not detectable by the Stroop task or Stroop task-related
      brain activation on fMRI. Moreover, there was no altered brain activity during
      the Stroop task after CBT-I. However, the ISI score reflected changes in the
      neural correlates of cognitive processes in patients with CID after CBT-I.

PMID- 29451995
TI  - Sex-Dependent Choroidal Thickness Differences in Healthy Adults: A Study Based on
      Original and Synthesized Data.
AB  - PURPOSE: The purpose of this study is to determine the influence of sex on
      choroidal thickness (CT) in healthy adults. METHODS: Healthy Chinese adults were
      recruited and complete ophthalmic examinations were performed. The choroid was
      imaged by swept-source optical coherence tomography and the macular CT in Early
      Treatment Diabetic Retinopathy Study grids was obtained by the intrinsic
      automated segmentation software. CT in males and females was compared after
      controlling other factors. All of the published studies in PubMed were
      systemically tracked, and a syntheses analysis of the combined data of the
      present study and previous studies was performed to address this issue further.
      RESULTS: A total of 104 healthy adults were included, of whom 38 (37%) were male
      and 66 (63%) were female. Older age and longer axial length (AL) each were
      significantly associated with thinner CT. After controlling for age and AL, the
      foveal CT and average macular CT were 25.5 MUm (95% CI: 0.5-50.4 MUm) and 22.1
      MUm (95% CI: 2.7-41.4 MUm) thicker in men than in women, respectively.
      Significant differences in CT between males and females were also observed in
      inner and outer rings after controlling for age and AL (P < 0.05). After strict
      screening, 15 previously reported studies were determined to be eligible for
      inclusion. The combination of data collected from 2821 males and 3389 females
      provided further evidence that the choroid is thicker in males, with a pooled
      mean difference of 19.5 MUm (95% CI: 11.4 to 27.6) for foveal CT and 14.7 MUm
      (95% CI: 6.8 to 22.6) for average CT. CONCLUSION: Our study of Chinese subjects,
      along with the syntheses analysis, strengthens the evidence that CT is greater in
      males than in females, based on OCT measurements. This observation may be
      pertinent for the sex disparities in some clinical conditions related to CT.

PMID- 29451996
TI  - Foveal Avascular Zone Area Changes Analyzed Using OCT Angiography after
      Successful Rhegmatogenous Retinal Detachment Repair.
AB  - PURPOSE: To investigate foveal avascular zone (FAZ) area after surgery in
      patients with rhegmatogenous retinal detachment (RRD) that involved or uninvolved
      the macula, and to evaluate the correlation between FAZ area and visual outcomes
      using swept-source optical coherence tomography angiography (OCTA). MATERIALS AND
      METHODS: This retrospective case-control study included 34 eyes (34 patients)
      with recent onset RRD that were successfully repaired with a single,
      uncomplicated surgical procedure (pars plana vitrectomy with gas tamponade). The
      changes of FAZ area were examined by OCTA after surgery. The unaffected fellow
      eye was used as a control for additional comparison. RESULTS: Both superficial
      and deep FAZ area were significantly larger in the macula-off group (superficial:
      0.374 +/- 0.112, deep: 0.702 +/- 0.193 mm2) than in the macula-on group
      (superficial: 0.282 +/- 0.105, deep: 0.543 +/- 0.114 mm2) following surgery. The
      deep FAZ area was also markedly larger in the macula-off group than in the
      control group (0.532 +/- 0.124 mm2). Correlation analyses revealed that both
      superficial (rho = 0.555, P = 0.015) and deep FAZ (rho = 0.616, P = 0.005) areas
      were negatively correlated with postoperative best-corrected visual acuity in the
      macula-off RRD group. CONCLUSIONS: The FAZ area enlargement after successful
      surgical repair in macula-off RRD eyes may indicate that there is an ischemic
      damage to retinal capillary plexus in fovea.

PMID- 29451997
TI  - Poly(lactic-co-glycolic) Acid as a Slow-Release Drug-Carrying Matrix for
      Methotrexate Coated onto Intraocular Lenses to Conquer Posterior Capsule
      Opacification.
AB  - PURPOSE: Posterior capsule opacification (PCO) still represents the main long
      term complication of cataract surgery. Research into pharmacologic PCO
      prophylaxis is extensive. One promising candidate drug is methotrexate (MTX). Our
      aim is to determine the in vitro feasibility of MTX-loaded poly(lactic-co
      glycolic) (PLGA) biomatrices sprayed on intraocular lenses (IOLs) as a drug
      delivery implant. METHODS: Hydrophilic and hydrophobic acrylic IOLs were spray
      coated with MTX-loaded PLGA. Unsprayed, solvent only, and solvent-PLGA-sprayed
      IOLs served as controls. All IOLs were evaluated for their growth-inhibiting
      properties in an in vitro anterior segment model and the ex vivo human capsular
      bag. The release kinetics of MTX from the IOLs was determined. The toxicity of
      MTX on corneal endothelial cells was evaluated by using a dye reduction
      colorimetric assay. MTX was also used in a scratch assay. RESULTS: MTX-PLGA-IOL
      showed a significant difference in cell proliferation and migration compared with
      all controls in the anterior segment model (p < 0.001) and in the human capsular
      bag model (p = 0.04). No difference in viability was observed on corneal
      endothelial cells (p = 0.43; p = 0.61). MTX significantly inhibited cells in the
      scratch assay (p = 0.02). At all measured points, the released MTX dose remained
      above EC50 and below the toxic dose for the endothelium. CONCLUSIONS: In view of
      the strong inhibition of PCO in vitro with the lack of toxic effects on a corneal
      cell line, MTX encapsulating microspheres seem to be a promising method for
      modifying IOL.

PMID- 29451998
TI  - Predicting the Integrated Visual Field with Wide-Scan Optical Coherence
      Tomography in Glaucoma Patients.
AB  - PURPOSE: This study aimed to calculate a predicted integrated visual field (IVF)
      based on predicted monocular visual fields (MVFs) derived, with a new method,
      from wide-scan optical coherence tomography (OCT) data. MATERIALS AND METHODS:
      Visual field testing used the central (6 * 4) 24 points of the Humphrey Field
      Analyzer 24-2 program. OCT scans of a corresponding retinal area, centered on the
      fovea, were divided into a 6 * 4 grid. The thickness of the macular retinal nerve
      fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCIPL), and
      mRNFL + GCIPL (GCC) was measured in each grid area. Next, a support vector
      machine was used to create a MVF prediction model, with training data from 101
      eyes of 60 glaucoma patients. Then, the prediction model was validated with data
      from 108 eyes of 54 glaucoma patients, for MVF and IVF. A simulated IVF was
      created by merging bilateral simulated MVFs. RESULTS: The overall average of the
      median 95% prediction interval length for the MVF prediction model (measured in
      dB) was 10.0, 18.3, and 11.3 for the mRNFL, GCIPL, and GCC, respectively. In the
      validation data, the overall average root mean squared error (dB) between actual
      and predicted sensitivity for the IVF was 9.6, 10.5, and 9.5 for the mRNFL,
      GCIPL, and GCC, respectively, in the 24 grid areas. The intraclass correlation
      coefficient between average actual and predicted IVF was 0.61, 0.44, and 0.59 in
      the mRNFL, GCIPL, and GCC, respectively, in the 24 grid areas. CONCLUSIONS: We
      calculated a predicted IVF based on predicted MVFs that were derived, with a new
      method, from OCT data and validated the accuracy of the calculated IVF. This
      technique should improve glaucoma management in cases when standard visual field
      testing is difficult.

PMID- 29451999
TI  - Evaluation of the Effects of the Occlu-Pad for the Management of Anisometropic
      Amblyopia in Children.
AB  - PURPOSE: In recent years, amblyopia treatment device that can be used with both
      eyes open have been reported. The Occlu-pad is a device that can present images
      of tablet terminals to one eye only under binocular open conditions. Till date,
      no study has reported the effectiveness of Occlu-pad training for anisometropic
      amblyopia in a series of cases. In the present study, we evaluated the
      effectiveness of the Occlu-pad for the management of anisometropic amblyopia
      without the use of occlusion therapy (eyepatch). MATERIALS AND METHODS: We
      implemented Occlu-pad training for 22 children (mean age +/- standard deviation:
      4.7 +/- 1.2 years) with anisometropic amblyopia. The visual acuity before
      treatment initiation was 0.25 +/- 0.08. The difference in refraction between the
      healthy and amblyopic eyes was 3.10 +/- 0.58 D. RESULTS: The visual acuity at 3
      months and 6 months after training initiation was 0.06 +/- 0.09 and -0.04 +/-
      0.07, respectively; this indicates a significant improvement in vision. The
      compliance rates for Occlu-pad use during 0 - 3 months and 4 - 6 months after
      training initiation were 88.6% +/- 18.9% and 73.2% +/- 18.9%; these rates
      decreased significantly with time. CONCLUSIONS: Our findings suggest that the
      Occlu-pad is an effective tool for the management of anisometropic amblyopia in
      children.

PMID- 29452000
TI  - Optimal Items for Assessing Sluggish Cognitive Tempo in Children Across Mother,
      Father, and Teacher Ratings.
AB  - A recent meta-analysis identified optimal items for assessing sluggish cognitive
      tempo (SCT) as distinct from attention deficit/hyperactivity disorder inattention
      (ADHD-IN), and a preliminary study with teacher ratings of children in the United
      States found strong support for the convergent and discriminant validity of 15
      SCT items. The current study evaluated whether the same 15 SCT items demonstrated
      convergent and discriminant validity from ADHD-IN in a large, community-based
      sample of children in Spain, and whether validity results were replicated across
      mother, father, and teacher ratings. Mothers, fathers, and teachers completed
      measures of SCT, ADHD-IN, ADHD-hyperactivity/impulsivity, oppositional defiant
      disorder, limited prosocial emotions, anxiety, depression, shyness, peer
      rejection, social impairment, and academic impairment on 2,142 Spanish children
      (49.49% girls; ages 8-13). The 15 SCT symptoms demonstrated convergent validity
      along with discriminant validity with ADHD-IN across all three informants. The
      SCT symptom ratings also showed measurement invariance across the informants. In
      addition, SCT and ADHD-IN factors had different and unique associations with the
      other symptom and impairment factors. The 15 SCT symptoms identified in this
      study-consistent across mother, father, and teacher ratings-appear appropriate to
      serve as a standard symptom set for assessing SCT in children. Use of a common
      set of symptoms in future studies will advance our understanding of the SCT
      construct, including its etiology and developmental progression, associations
      with ADHD and other psychopathologies, links to impairment, and implications for
      clinical intervention.

PMID- 29452001
TI  - Sexual Behavior With Noncommercial Partners: A Concurrent Partnership Study Among
      Middle-Aged Female Sex Workers in China.
AB  - Female sex workers (FSWs) often engage in concurrent partnerships, meaning they
      have multiple sexual relationships at the same time. The objective of this study
      was to investigate sexual concurrency and its associations with condom use and
      syphilitic infections among FSWs over age 35. Respondent-driven sampling was used
      to recruit 1,245 FSWs in Nanning, Hefei, and Qingdao, China. FSWs were asked to
      report whether they had concurrent partners in the past six months. Concurrency
      was defined as engagement in sex with commercial clients and (1) husbands and
      boyfriends (n = 167); (2) husbands only (n = 301); or (3) boyfriends only (n =
      469). FSWs with only commercial clients were used as the comparison group (n =
      308). Across all groups, the percentage of FSWs with prevalent and active
      syphilis ranged from 19.6% to 25.6% and 9.1% to 11.5%, respectively. Condom use
      was low with noncommercial sexual partners and was more likely to be used when
      FSWs' boyfriends had other partners. Three components of the theory of planned
      behavior were significantly associated with consistent condom use. Concurrent
      relationships may lead to increased transmission of syphilis at the workplace and
      family levels. Effective interventions should target concurrency with both
      commercial and noncommercial partners.

PMID- 29452002
TI  - Conditions-Based Learning Theory as a Framework for Comparative-Effectiveness
      Reviews: A Worked Example.
AB  - : Phenomenon: An evidence-informed era of medical education encourages the
      generation and use of comparative-effectiveness reviews, yet the reviews often
      conclude, curiously, that all instructional approaches are equally effective.
      APPROACH: We used a conditions-based learning theory to structure a review of the
      comparative-effectiveness literature on electrocardiogram instruction. We
      searched MEDLINE, EMBASE (Ovid), ERIC (Ovid), PsycINFO (Ovid), and CINAHL (EBSCO)
      from inception to June 2016. We selected prospective studies that examined the
      effect of instructional interventions on participants' knowledge and skill with
      electrocardiogram interpretation. Two reviewers extracted information on the
      quality of the studies, the effect of instruction on the acquisition of knowledge
      and skill, and instructional quality. Instructional quality is an index of the
      extent to which instruction incorporates 4 practices of Gagne's conditions-based
      learning theory: presenting information, eliciting performance, providing
      feedback, and assessing learning. FINDINGS: Twenty-five studies (3,286
      participants) evaluating 47 instructional interventions were synthesized. The
      methodological quality of most studies was moderate. Instructional quality
      varied: All interventions presented information and assessed learning, but fewer
      than half elicited performances or provided feedback. Instructional interventions
      that incorporated all 4 components improved trainees' abilities considerably more
      than those that incorporated 3 or fewer; respectively, standardized mean
      difference (SMD) = 2.80, 95% confidence interval (CI) [2.05, 3.55], versus SMD =
      1.44, 95% CI [1.18, 1.69]. Studies that compared "innovative" to "traditional"
      types of instruction did not yield a significant pooled effect: SMD = 0.18, 95%
      CI [-0.09, 0.45]. Insights: The use of a conditions-based learning theory to
      organize the comparative-effectiveness literature reveals differences in the
      instructional impact of different instructional approaches. It overturns the
      unlikely, but common, conclusion that all approaches are equally effective.

PMID- 29452003
TI  - Acute pneumopericardium: when echocardiography is not enough.

PMID- 29452004
TI  - Review of Literature on Measurements of Non-invasive Break Up Times, Lipid
      Morphology and Tear Meniscal Height Using Commercially Available Hand-held
      Instruments.
AB  - : Purpose/aims: Dry eye is a common multi-factorial disease characterized by
      tearfilm dysfunction. Diagnosis of dry eye requires documentation of tear status
      with non-invasive tear break up times (NIBUT), tear meniscal height (TMH), and
      tearfilm lipid layer. These parameters objectively assess tear stability and
      indirectly, the functional impact of meibomian gland dysfunction. While it is
      obvious that portable instrumentation gives broader access than fixed
      instrumentation, its value would be limited if it is unreliable and its precision
      and accuracy substantially worse than fixed instruments. MATERIALS/METHODS:
      Because of the lack of systematic reviews concerning the Tearscope, we performed
      a scoping review of the literature to determine 1. the ranges of the tear
      parameters as measured by the device, 2. relationship between these measurements
      and other clinical variables, 3. Information about intra or inter-observer
      agreement, and comparison with another technique, where available. RESULTS: We
      found 22 reports related to NIBUT, 18 reports concerning tearfilm lipid
      morphology (LM) based on classification of interference patterns, and 8 reports
      on TMH. While publication of these reports indicates an acceptance of the
      reliability of portable instruments, we interrogated these studies further to
      evaluate the results obtained from portable devices and found that there was no
      equivalent measurements in fixed devices (LM) or measurements differ considerably
      from fixed devices (NIBUT). In the case of TMH, portable measurements were
      similar to those by traditional slit-lamp microscopy. There were relatively few
      studies on TMH measured using handheld devices, but it was found to be correlated
      to NIBUT but not the Schirmer test values. CONCLUSIONS: Imaging algorithms in
      portable tearfilm instruments should be further standardized to facilitate wider
      adoption and evaluation. In the next few years, new emerging technologies will
      employ a strategy of non-invasive tear testing that is portable and relatively
      inexpensive, and these will enhance adoption of such tools in the clinic.

PMID- 29452005
TI  - American Academy of Hospice and Palliative Medicine: Dedicated to Prevention and
      Relief of Suffering.

PMID- 29452006
TI  - Falling Through the Cracks: Young Adults and Cancer-The Ulman Cancer Fund for
      Young Adults.

PMID- 29452007
TI  - 2006 Update of the ASCO Recommendations for Antiemetics in Oncology: Guideline
      Summary.

PMID- 29452008
TI  - An Interview With Peter Greenwald, MD, PhD.

PMID- 29452009
TI  - Avoiding the Trauma of Courtroom Drama.

PMID- 29452010
TI  - Wooing the Reluctant Fellow: State Societies Face Similar Problems When
      Recruiting Fellows.

PMID- 29452011
TI  - Deciding About Practice Options.

PMID- 29452012
TI  - Following the Pipeline.

PMID- 29452013
TI  - 2006 Update of ASCO Practice Guideline Recommendations for the Use of White Blood
      Cell Growth Factors: Guideline Summary.

PMID- 29452015
TI  - PLWC Editorial Board Expands Peer-Reviewed Cancer-Type Sections.

PMID- 29452014
TI  - Preparing for Clinical Trial Data Audits.

PMID- 29452016
TI  - The Effect of Rap/Hip-Hop Music on Young Adult Smoking: An Experimental Study.
AB  - BACKGROUND: Music may influence young people's behavior through its lyrics.
      Substance use references occur more frequently in rap/hip-hop than in other music
      genres. OBJECTIVES: The aim was to examine whether the exposure to rap/hip-hop
      lyrics referring to substance use affected cigarette smoking. METHODS: An
      experiment with a 3-group between subject design was conducted among 74 daily
      smoking young adults ranging in age from 17 to 25 years old. Three conditions
      were tested in a mobile lab (camper vehicle) from May to December 2011, i.e.,
      regular chart pop music (N = 28), rap/hip-hop with non-frequent references to
      substance use (N = 24), and rap/hip-hop with frequent references to substance use
      (N = 22). RESULTS: One-way ANOVA showed that participants listening to substance
      use infused rap/hip-hop songs felt significantly less pleasant, liked the songs
      less, and comprehended the songs less compared to participants listening to pop
      songs. Poisson loglinear analyses revealed that compared to the pop music
      condition, none of the two rap/hip-hop music conditions had a significant effect
      on acute smoking. Thus, contrary to expectations, the two different rap/hip-hop
      conditions did not have a significantly different effect on acute smoking.
      CONCLUSIONS: Listening to rap/hip-hop, even rap hip/hop with frequent referrals
      to substance use (primarily alcohol and drug use, and general smoking referrals),
      does not seem to encourage cigarette smoking among Dutch daily-smoking young
      adults, at least short term.

PMID- 29452017
TI  - Fractional non-ablative laser-assisted drug delivery leads to improvement in male
      and female pattern hair loss.
AB  - Androgenetic alopecia, also known as male and female pattern hair loss, is a very
      prevalent condition; however, approved therapeutic options are limited.
      Fractionated laser has been proposed to assist in penetration of topical
      medications to the cutaneous tissue. We present four cases of androgenetic
      alopecia that underwent treatment with a non-ablative erbium glass fractional
      laser followed by the application of topical finasteride 0,05% and growth factors
      including basic fibroblast growth factor, insulin-like growth factor, vascular
      endothelial growth factor, and copper peptide 1%. During all laser treatment
      sessions, eight passes were performed, at 7 mJ, 3-9% of coverage and density of
      120 mzt/cm2. A positive response was observed in all of the four patients.
      Photographs taken 2 weeks after the last session showed improvement in hair
      regrowth and density. No significant side effects were observed.

PMID- 29452019
TI  - American Society of Clinical Oncology Clinical Practice Guideline Update on the
      Use of Pharmacologic Interventions Including Tamoxifen, Raloxifene, and Aromatase
      Inhibition for Breast Cancer Risk Reduction.
AB  - ASCO's update to its Clinical Practice Guideline on the use of pharmacologic
      interventions to reduce the risk of breast cancer addresses the roles of
      tamoxifen, raloxifene, aromatase inhibitors, and fenretinide in reducing risk for
      the disease.

PMID- 29452018
TI  - E-Prescribing: Worth the Effort?
AB  - The Medicare Improvements for Patients and Providers Act of 2008 includes an
      incentive program for electronic prescribing, but oncologists report significant
      difficulties in the program's design and in using available products.

PMID- 29452020
TI  - Participating in Medicare's E-Prescribing Incentive Program.

PMID- 29452021
TI  - Erratum.

PMID- 29452022
TI  - Marketing to Members Through E-Mail and Word of Mouth.

PMID- 29452023
TI  - Practice.

PMID- 29452024
TI  - Factors shaping expectations for complete relief from symptoms during
      rehabilitation for patients with spine pain.
AB  - OBJECTIVE: Patient expectations are related to treatment outcome across a broad
      variety of patient conditions. Here we sought to examine factors associated with
      the expectation of complete relief from treatment for spinal pain. DESIGN:
      Secondary analysis of data pooled from two randomized controlled trials of
      conservative rehabilitation interventions. PATIENTS: 252 patients (103 men, 149
      women) with neck (n = 140) or back (n = 112) pain. METHODS: We used logistic
      regression model with backward elimination to test which patient clinical or
      demographic factors were most related to the expectation of complete relief. MAIN
      OUTCOME MEASURES: The expectation of complete recovery, which was collected at
      the baseline examination visit in the primary trials. RESULTS: The final model
      examining the contributions of patient and clinical characteristics to the
      expectation of complete relief included two significant interactions. First,
      increasing disability was associated with increased odds of expecting complete
      recovery in women while there was very little change for men across levels of
      disability (OR 0.9 [95%CI 0.8, 0.9]). Second, patients with low fear and a sudden
      onset of pain had higher odds of expecting recovery than patients with a gradual
      onset of pain (OR 0.7 [95%CI 0.5, 0.97]). A main effect for education level of
      the patient was also significant with better odds for expecting complete recovery
      for college educated patients compared to those with graduate school education
      (OR 5.0 [95%CI 1.9, 13.4]). CONCLUSION: The results should assist physical
      therapists to recognize patients who may have lower expectations of recovery and
      plan pre-treatment education interventions.

PMID- 29452025
TI  - Subgrouping the users of a specialized app for eating disorders.
AB  - Although mobile technologies for eating disorders (EDs) are burgeoning, there is
      limited data about the clinical characteristics of individuals using specialized
      smartphone applications (apps) without accompanying traditional forms of
      treatment. This study evaluated whether the users of an ED app cluster in
      clinically meaningful groups. Participants were 1,280 app users (91.3% female;
      mean age 27) who reported not being in a weekly treatment for their ED. A
      hierarchical cluster analysis distinguished five groups of participants, all
      approximating DSM-5 ED categories. One cluster comprised of non-female,
      ethnically diverse users with Bulimia Nervosa features. Findings suggest that app
      users resemble known patient classifications.

PMID- 29452026
TI  - General movements and motor outcomes in two infants exposed to Zika virus: brief
      report.
AB  - OBJECTIVE: We described the general movements (GMs) in the fidgety period and the
      motor performance of two infants who were exposed to Zika virus (ZIKV) during
      distinct trimesters of gestation. METHODS: Infants were assessed at 4 and 12
      months of age. Prechtl's GM assessment and the Alberta Infant Motor Scale were
      used. RESULTS: In Case 1, the mother presented confirmed ZIKV infection in the
      10th week of gestation and the infant was born full-term with brain abnormalities
      and microcephaly. Fidgety movements were absent at 16 weeks after term and motor
      development was severely impaired at 12 months of age. In Case 2, the mother
      presented confirmed ZIKV infection in the 34th week of gestation and the infant
      was born full-term with no signs of brain changes or microcephaly. Fidgety
      movements at 13 weeks were normal in presentation and motor outcome was typical
      at 12 months. CONCLUSION: GM assessment can be useful for ZIKV-exposed infants.
      These findings represent the first information on GMs and long-term motor
      outcomes in ZIKV-exposed infants.

PMID- 29452027
TI  - Short interval overnight laser scanning suggests sub-circadian periodicity of
      tree turgor.
AB  - A recent study by Zlinszky et al., 1 uses high-resolution terrestrial laser
      scanning to investigate the variability of overnight movement of leaves and
      branches in vascular plants. This study finds among others that the investigated
      plants show periodic movements of around one centimetre in amplitude and 2-6 hour
      periodicity. Sub-circadian process dynamics of plants were so far not in focus of
      research, but here we compare the findings with other published cases of short
      term periodicity in leaf turgor, sap flow and especially trunk diameter. Several
      authors have noted overnight variations in these parameters within periods of
      several hours and in absence of environmental changes with similar dynamics. We
      revisit the unknown questions of short-term plant movement and make a suggestion
      for future research.

PMID- 29452029
TI  - Intense pulsed light is effective in treating postburn hyperpigmentation and
      telangiectasia in Chinese patients.
AB  - Intense pulsed light (IPL) has been used to treat postinflammatory
      hyperpigmentation and telangiectasia in Fitzpatrick type I -II skin. However, its
      therapeutic effects after superficial second-degree burns in Asian populations
      with Fitzpatrick type III-IV skin are uncertain. Thirty-five Han Chinese patients
      with facial or hand hyperpigmentation and telangiectasia due to second-degree
      fire burns received treatment with IPL. Each patient underwent 2-6 treatments
      over 3-5 weeks. The laser wavelength was 560-615 nm. Skin pigmentation was
      evaluated by two plastic surgeons as well as by the patients themselves (self
      evaluation) before treatment at the end of the treatment cycle and 1 year after
      the first treatment. Blood flow in telangiectasia skin was measured by laser
      Doppler flow. The results showed that IPL significantly lessened
      hyperpigmentation so that close to normal skin color was achieved after the
      treatment cycles, and pigmentation did not reoccur 1 year after the first
      treatment. Approximately 82.9% of the patients were satisfied with their
      treatment outcomes. There were no post-treatment complications. Doppler showed a
      significant decreased blood flow in telangiectasia after treatment. In
      conclusion, IPL is an effective and safe modality for Chinese patients with
      hyperpigmentation and telangiectasia after fire burns.

PMID- 29452028
TI  - Meningococcal disease and vaccination: Knowledge and acceptability among
      adolescents in Italy.
AB  - This study aimed to evaluate the knowledge, attitudes and practice about invasive
      meningococcal disease and the relative vaccine for adolescent in Italy. A cross
      sectional study was conducted from March to May 2017 among a sample of 771
      adolescents in the geographic area of Naples (Italy). A self-administered
      anonymous questionnaire was used to collect demographics, knowledge about
      meningitis and preventive measures, perceived risk for contracting meningitis,
      attitude towards the utility of meningococcal vaccine, and adolescents'
      willingness to receive a meningococcal vaccine. 85.2% of participants have heard
      about meningitis, 57.2% knew that adolescents are a susceptible population but
      only 30.3% knew that meningitis is transmitted by respiratory droplets. Moreover,
      40.5% of adolescents knew that meningitis is a vaccine-preventable disease and
      that adolescents could be vaccinated. This knowledge was significantly greater
      among female participants, among those who talk with parents about vaccinations,
      among who have received information about vaccinations from physicians, among who
      have positive attitude towards the utility of information received on
      vaccinations and among who don't feel the need of additional information about
      meningitis. As regard the attitudes, 25.7% of adolescents thought that the
      vaccine was very useful. Males, adolescent aged 11-13 years, those who had the
      positive attitude towards the utility of information received about vaccinations
      and those who had received at least one vaccination in the last year were more
      likely to have this attitude. The our finding identifies the need to improve
      adolescents' knowledge about meningitis and its related vaccinations, through
      correct health education, in order to have a good acceptance of vaccination.

PMID- 29452032
TI  - Ensure the Future of Your Practice Through Early Succession Planning.
AB  - Key physicians may leave at any time, and your group must be ready to fill the
      remaining gaps. Written succession plans keep you prepared for departures from
      your group and help you maintain the loyalty of your patients by providing them
      with seamless care.

PMID- 29452031
TI  - Prehospital Cervical Spine Motion: Immobilization Versus Spine Motion
      Restriction.
AB  - OBJECTIVE: This study aims to evaluate the efficacy of two different spinal
      immobilization techniques on cervical spine movement in a simulated prehospital
      ground transport setting. METHODS: A counterbalanced crossover design was used to
      evaluate two different spinal immobilization techniques in a standardized
      environment. Twenty healthy male volunteers (age = 20.9 +/- 2.2 yr) underwent
      ambulance transport from a simulated scene to a simulated emergency department
      setting in two separate conditions: utilizing traditional spinal immobilization
      (TSI) and spinal motion restriction (SMR). During both transport scenarios,
      participants underwent the same simulated scenario. The main outcome measures
      were cervical spine motion (cumulative integrated motion and peak range of
      motion), vital signs (heart rate, blood pressure, oxygen saturation), and self
      reported pain. Vital signs and pain were collected at six consistent points
      throughout each scenario. RESULTS: Participants experienced greater transverse
      plane cumulative integrated motion during TSI compared to SMR (F1,57 = 4.05; P =
      0.049), and greater transverse peak range of motion during participant
      loading/unloading in TSI condition compared to SMR (F1,57 = 17.32; P < 0.001).
      Pain was reported by 40% of our participants during TSI compared to 25% of
      participants during SMR (chi2 = 1.29; P = 0.453). CONCLUSIONS: Spinal motion
      restriction controlled cervical motion at least as well as traditional spinal
      immobilization in a simulated prehospital ground transport setting. Given these
      results, along with well-documented potential complications of TSI in the
      literature, SMR is supported as an alternative to TSI. Future research should
      involve a true patient population.

PMID- 29452030
TI  - Comparative phylogenetic and expression analysis of small GTPases families in
      legume and non-legume plants.
AB  - BACKGROUND: Small monomeric GTPases act as molecular switches in several
      processes that involve polar cell growth, participating mainly in vesicle
      trafficking and cytoskeleton rearrangements. This gene superfamily has largely
      expanded in plants through evolution as compared with other Kingdoms, leading to
      the suggestion that members of each subfamily might have acquired new functions
      associated to plant-specific processes. Legume plants engage in a nitrogen-fixing
      symbiotic interaction with rhizobia in a process that involves polar growth
      processes associated with the infection throughout the root hair. To get insight
      into the evolution of small GTPases associated with this process, we use a
      comparative genomic approach to establish differences in the Ras GTPase
      superfamily between legume and non-legume plants. RESULTS: Phylogenetic analyses
      did not show clear differences in the organization of the different subfamilies
      of small GTPases between plants that engage or not in nodule symbiosis. Protein
      alignments revealed a strong conservation at the sequence level of small GTPases
      previously linked to nodulation by functional genetics. Interestingly, one Rab
      and three Rop proteins showed conserved amino acid substitutions in legumes, but
      these changes do not alter the predicted conformational structure of these
      proteins. Although the steady-state levels of most small GTPases do not change in
      response to rhizobia, we identified a subset of Rab, Rop and Arf genes whose
      transcript levels are modulated during the symbiotic interaction, including their
      spatial distribution along the indeterminate nodule. CONCLUSIONS: This study
      provides a comprehensive study of the small GTPase superfamily in several plant
      species. The genetic program associated to root nodule symbiosis includes small
      GTPases to fulfill specific functions during infection and formation of the
      symbiosomes. These GTPases seems to have been recruited from members that were
      already present in common ancestors with plants as distant as monocots since we
      failed to detect asymmetric evolution in any of the subfamily trees. Expression
      analyses identified a number of legume members that can have undergone neo- or
      sub-functionalization associated to the spatio-temporal transcriptional control
      during the onset of the symbiotic interaction.

PMID- 29452033
TI  - Medicare Coverage Criteria for Oral and Intravenous Antiemetics.

PMID- 29452034
TI  - Introduction.

PMID- 29452035
TI  - Strategic Planning: Why It Makes a Difference, and How to Do It.
AB  - Take action before problems reach crisis level. Strategic planning provides the
      structure to make day-to-day decisions that follow a larger vision, creates a
      direction for your practice, and maximizes your options for influencing your
      environment.

PMID- 29452037
TI  - Survivorship Information: Where Patients Learn "What Comes Next".

PMID- 29452036
TI  - Drug Shortages: Resources for Assistance.

PMID- 29452038
TI  - Use of 5-alpha-Reductase Inhibitors for Prostate Cancer Chemoprevention: American
      Society of Clinical Oncology/American Urological Association 2008 Clinical
      Practice Guideline Summary.
AB  - of recommendations from ASCO and the American Urological Association regarding
      the chemoprevention of prostate cancer and use of 5-alpha-reductase inhibitors.

PMID- 29452039
TI  - To Survive-What a Great Problem to Have!

PMID- 29452040
TI  - Progress in the Control of Chemotherapy-Induced Emesis: New Agents and New
      Studies.
AB  - New agents and studies have demonstrated benefit in improving antiemetic therapy.
      Incorporating evidence-based guideline recommendations and appropriate emesis
      assessments are key components to achieving the best practice.

PMID- 29452041
TI  - Developing the ASCO Lung Cancer Treatment Plans and Summaries.

PMID- 29452042
TI  - Real-life closeness of social media contacts and depressive symptoms among
      university students.
AB  - OBJECTIVE: To examine the association between degree of real-life closeness of
      social media (SM) contacts and depressive symptoms. PARTICIPANTS: Students ages
      18-30 (N = 1124) were recruited in August 2016. METHODS: Participants completed
      an online survey assessing SM use and depression. We used multivariable logistic
      regression to assess associations between real-life closeness of SM contacts and
      depressive symptoms. RESULTS: After controlling for covariates, each 10% increase
      in the proportion of SM friends with whom participants had no face-to-face
      relationship was associated with a 9% increase in odds of depressive symptoms
      (AOR = 1.09; 95% CI = 1.05-1.13). However, each 10% increase in the proportion of
      SM friends with whom participants had a close face-to-face relationship was
      associated with a 7% decrease in depressive symptoms (AOR = 0.93; 95% CI = 0.89
      0.97). CONCLUSIONS: Having no in-person relationship with SM contacts is
      associated with increased depressive symptoms; however, having close in-person
      relationships with SM contacts is associated with decreased depressive symptoms.

PMID- 29452043
TI  - Citizens' Jury and Elder Care: Public Participation and Deliberation in Long-Term
      Care Policy in Thailand.
AB  - Health care policies for the elderly are complex, multidimensional, and
      contextually circumscribed. While engagement of health experts, economists,
      health care administrators, and political leaders is generally viewed as
      instrumental to the success and sustainability of eldercare programs, the elders
      themselves are often viewed as passive recipients of care and not included in the
      policy processes. Experiences and expectations from users' perspectives can be
      invaluable information for policy formulation and systems design. This paper
      examines a participatory policy process using a "citizens' jury" to promote
      public engagement in eldercare policy. The process was initiated by the National
      Health Commission Office in Thailand to explore how a citizens' jury as a model
      for civic deliberation can be utilized to provide sophisticated policy
      recommendations on long-term care policies for the elderly. The objectives of
      this paper are to (1) examine how public participation in health policy can be
      actualized through the citizens' jury as an operational model, (2) understand the
      strengths and weaknesses of the ways the idea was implemented, and (3) provide
      recommendations for further use of the model. Details of how a citizens' jury was
      deployed are discussed, with recommendations for further use provided at the end.

PMID- 29452044
TI  - Food Addiction is Associated with Higher Neuroticism, Lower Conscientiousness,
      Higher Impulsivity, but Lower Extraversion in Obese Patient Candidates for
      Bariatric Surgery.
AB  - BACKGROUND: The "food addiction" phenotype identifies a subpopulation of
      individuals experiencing substance-dependence symptoms toward specific foods. In
      the current debate on whether the "food addiction" phenotype should be considered
      as an addictive disorder, assessment of the personality traits associated with
      this phenotype would provide arguments for or against the "food addiction"
      phenotype and its inclusion in the "substance-related and addictive disorder"
      category. OBJECTIVES: To assess the personality characteristics associated with
      the "food addiction" phenotype in obesity surgery candidates (i.e., big five
      personality dimensions, alexithymia and impulsivity). METHODS: We assessed food
      addiction (Yale Food Addiction Scale), personality dimensions (Big Fig
      Inventory), impulsivity (Barratt Impulsiveness Scale-11th version) and
      alexithymia (Toronto Alexithymia Scale-20 items) in 188 bariatric surgery
      candidates recruited between July 2013 and November 2015 in the Nutrition
      Department of the University Hospital of Tours. We used chi-squared tests and
      Student's tests or Mann-Whitney-U-tests to determine the factors associated with
      food addiction. RESULTS: Prevalence of current food addiction was 16.5%. Patients
      with (vs. without) food addiction had lower conscientiousness (p = .047), higher
      neuroticism and lower extraversion (ps < 0.001), but there was no difference in
      terms of agreeableness (p = 0.42) or openness (p = 0.16). They were more
      frequently single (p = .021) and reported higher alexithymia (ps < .001) and
      higher impulsivity sub-scores (ps<.05). Conclusions/Importance: Food addiction
      shares personality traits with substance-related disorders (regarding
      neuroticism, conscientiousness, impulsivity, alexithymia), and one distinctive
      trait (low extraversion). This study provides additional data that enrich the
      discussion on whether the "food addiction" phenotype should be included or not in
      the "substance-related and addictive disorder" category.

PMID- 29452045
TI  - Successful treatment of Schamberg's disease with fractional non-ablative 1540 nm
      erbium:glass laser.
AB  - Schamberg's disease is one of the pigmented purpuric dermatoses (PPD). PPD
      encompass a large and heterogeneous group of dermatologic disorders featuring
      purpuric lesions often located on the lower limbs. The various forms of PPD are
      notoriously known to be resistant to treatment. Fractional photothermolysis has
      been described as a successful and safe method to induce dermal remodeling. We
      report three patients with Schamberg's disease who were successfully treated with
      4 monthly sessions of fractional non-ablative 1540 nm erbium:glass laser, with
      resolution of their purpuric pigmented rash lasting up to 9 months after the last
      treatment session.

PMID- 29452046
TI  - Neuroanniversary 2018.

PMID- 29452047
TI  - Lessons learned from Ebola Vaccine R&D during a public health emergency.
AB  - In spite of a complete lack of Research and Development (R&D) preparedness, the
      2013-2016 West-Africa Ebola experience demonstrated that it is possible to
      compress R&D timelines to less than a single year, from a more usual decade or
      longer. This is mostly to be credited to an unprecedented collaborative effort
      building on the availability of a small number of candidate diagnostic tests,
      drugs and vaccines that could be moved rapidly into the clinical phase
      evaluation. The World Health Organization (WHO) led international consultations
      and activities - including the organization of a successful Ebola vaccine
      efficacy trial in Guinea - as a contribution to the unprecedented global efforts
      to control the Ebola epidemic. Since 2015, WHO expert teams and partners are
      implementing a novel R&D model for emerging infectious pathogens which are the
      most likely to cause severe outbreaks in the future, and for which no or only few
      medical countermeasures are available: the WHO R&D Blueprint. The objective for
      the Blueprint is the fostering of a R&D environment which is prepared for quickly
      and effectively responding to outbreaks due to emerging infectious disease.

PMID- 29452049
TI  - Model-free tests of equality in binary data under an incomplete block design.
AB  - Using Prescott's model-free approach, we develop an asymptotic procedure and an
      exact procedure for testing equality between treatments with binary responses
      under an incomplete block crossover design. We employ Monte Carlo simulation and
      note that these test procedures can not only perform well in small-sample cases
      but also outperform the corresponding test procedures accounting for only
      patients with discordant responses published elsewhere. We use the data taken as
      a part of the crossover trial comparing two different doses of an analgesic with
      placebo for the relief of primary dysmenorrhea to illustrate the use of test
      procedures discussed here.

PMID- 29452048
TI  - High frequency of metronidazole and clarithromycin-resistant Helicobacter pylori
      in formalin-fixed, paraffin-embedded gastric biopsies.
AB  - BACKGROUND: Clarithromycin and metronidazole resistance of Helicobacter pylori is
      increasing worldwide and has resulted in a loss in the effectiveness of
      therapeutic regimens. We aimed to evaluate common mutations of resistance genes
      to clarithromycin (A2143G, A2142G and A2142C) and metronidazole (rdxA and frxA)
      in H. pylori strains in formalin-fixed, paraffin-embedded gastric biopsies.
      METHODS: A total of 110 tissue blocks from children suspected of H. pylori
      infection were included. After DNA extraction, UreC PCR was performed. Specific
      primers and restriction enzymes by PCR-RFLP were used for analysis of A2143G and
      A2142G mutations. To detect A2142C and assess frequent mutations of metronidazole
      resistance, specific primers and PCR method were used. RESULTS: One hundred cases
      of H. pylori (91%) were by PCR. Of 34 (34%) clarithromycin-resistant isolates 17
      (50%), 10 (29%) and 7 (21%) had A2143G, A2142G, A2142C, respectively. Resistance
      rate to metronidazole was 60% (N = 60). In sequencing rdxA and frxA in the
      mutated strains, missense mutations were most frequent (60 and 57%,
      respectively), and there were differences in frameshift and non-sense mutations
      (p < 0.001). CONCLUSION: Resistance rate to clarithromycin was high and the
      highest percentage of mutation was of A2143G. PCR-RFLP was used directly with
      formalin-fixed gastric biopsies, thus, avoiding the requirement for time
      consuming culture-based methods. The isolates that developed resistance were
      mainly associated with mutations of both rdxA and frxA genes.

PMID- 29452050
TI  - Pathways linking intergenerational cultural dissonance and alcohol use among
      Asian American youth: The role of family conflict, parental involvement, and peer
      behavior.
AB  - A difference in degree of acculturation between immigrant parents and children,
      known as intergenerational cultural dissonance (ICD), is a risk factor for
      adolescent alcohol use. We used path analysis with 292 Vietnamese and Cambodian
      adolescents from immigrant families in the United States to measure potential
      mediators (family conflict, parental involvement/monitoring, association with
      deviant peers) of the ICD-alcohol use relationship. The hypothesized model was an
      adequate data fit among both groups. Among Cambodian adolescents, higher ICD
      levels significantly predicted increased family conflict, which in turn was
      associated with reduced parental involvement/monitoring, increased association
      with deviant peers, and a subsequently higher risk of alcohol use (p < .05 for
      all coefficients). We also found significant indirect effects of ICD on alcohol
      use among Vietnamese adolescents through family conflict and parental
      involvement/monitoring (p < .05 for all coefficients) but not through peer
      behavior. For both groups, there was no direct effect of ICD on alcohol use
      outside these pathways. Identification of significant mediators provides
      potential targets for preventing alcohol use among these populations. In
      addition, differences in path coefficients between Vietnamese and Cambodian
      adolescents underscore the importance of conducting analyses stratified by Asian
      ethnic group.

PMID- 29452051
TI  - Using the Ecological Model to understand influences on college student vaping.
AB  - : Objective The Ecological Model was used to examine the social and environmental
      influences of the college environment on e-cigarette use (vaping) among college
      students. PARTICIPANTS: Undergraduate college student e-cigarette users (vapers)
      across three large college campuses in the southwest US from Jan 2015- Aug 2016.
      METHODS: Thirty-three interviews were conducted. Transcribed interviews were
      coded then analyzed for themes. RESULTS: College student vapers report multiple
      levels of influence on their vaping beyond personal beliefs and peer influences,
      including parents, explicit campus and community messaging, community member
      requests, and respect for others. College student vapers also describe constant
      associations with smokers in allowable public places to vape. CONCLUSIONS:
      Parents, community members, campus policy, and the physical environment all
      influence where and when college students vape. Health communication messages to
      prevent college student vaping should incorporate alternative messages that are
      important to college students, such as respect for others and social image.

PMID- 29452052
TI  - Agency and fatalism in older Appalachian women's information seeking about
      gynecological cancer.
AB  - Researchers consider older women in rural Appalachia to have low levels of agency
      and high levels of fatalism regarding decision making about cancer treatment.
      Using the life course perspective, we examined older women's agency with
      information seeking about gynecological cancer. Semistructured interviews with 20
      White women living in central Appalachia revealed four trajectories: Surrendering
      Control, Accepting Death, Self-Care, and Advocacy, each with its own forms of
      agency. Some women experienced personal transformation, increased self-efficacy,
      and a passion for community empowerment. Fatalism was not understood apart from
      placing trust in medical expertise. We implore researchers to further explore
      rural expressions of agency.

PMID- 29452053
TI  - Social adjustment and repressive adaptive style in survivors of pediatric cancer.
AB  - PURPOSE: The aim of the study was to explore the relationship between repressive
      adaptive style and self-reports of social adjustment in survivors of pediatric
      cancer compared to their siblings. We hypothesized that there would be a greater
      proportion of repressors among survivors of pediatric cancer compared to
      siblings, and that repressive adaptive style would be significantly associated
      with more positive self-reports of social adjustment. METHODS: We utilized a
      cross-sectional approach. Seventy-seven families participated. Survivors of
      pediatric cancer (n = 77, 48% male; 8-18 years of age) and one sibling (n = 50,
      48% male; 8-18 years of age) completed measures assessing repressive adaptive
      style and social adjustment. As well, one parent from each family completed a
      socio-demographic questionnaire. Questionnaire packages were mailed to eligible
      families who agreed to participate, and were mailed back to investigators in a
      pre-addressed, pre-stamped envelope. RESULTS: Chi-square analyses revealed there
      was no significant difference in the proportion of repressors among survivors and
      siblings. Social adjustment scores were subjected to a two (group: survivor,
      sibling) by two (repressor, nonrepressor) ANCOVA with gender and age as
      covariates. There was a significant main effect of repressive adaptive style (F =
      5.69, p < .05, eta2 = 0.05) with a modest effect. Survivors and siblings with a
      repressive style reported significantly higher social adjustment scores (M =
      106.91, SD = 11.69) compared to nonrepressors (M = 99.57, SD = 13.45).
      CONCLUSIONS: Repressive adaptive style explains some of the variance in survivors
      and siblings' self-reports of social adjustment. Future research should aim to
      better understand the role of the repressive adaptive style in survivors and
      siblings of children with cancer.

PMID- 29452054
TI  - Community resources support adherence to treatment for childhood cancer in El
      Salvador.
AB  - OBJECTIVE: In order to reduce nonadherence and treatment abandonment of children
      with cancer in El Salvador, institutions located nearby the patients' homes were
      involved to provide support. Methodological approach: Health clinics and
      municipality offices in the patients' communities were asked to assist families
      who were not promptly located after missing hospital appointments, or those whose
      financial limitations were likely to impede continuation of treatment. Data was
      collected about the number of contacted institutions, the nature of help
      provided, staff's time investments, and parents' perceptions about the
      intervention. FINDINGS: Local institutions (133 from 206 contacts) conducted home
      visits (83), and/or provided parents with money (55) or transportation (60).
      Parents found this support essential for continuing the treatment but they also
      encountered challenges regarding local institutions' inconsistencies.
      Nonadherence and abandonment decreased. IMPLICATIONS: Economic burden was reduced
      on both the families and the hospital. Involvement of external institutions might
      become regular practice to support families of children with cancer.

PMID- 29452055
TI  - Feeling an Invisible Wall: The Experience of Iranian Women's Marital Relationship
      After Surgical Menopause: A Qualitative Content Analysis Study.
AB  - Sexual relationships after surgical menopause matter when talking about sex is
      taboo and marriage is the only justified way to meet sexual needs. In this
      qualitative research study, 22 surgical menopausal women shared their experiences
      of sexual/marital relationship after surgery through in-depth, face-to-face, semi
      structured interviews. Qualitative content analysis technique was used for data
      analysis. An overarching theme entitled "feeling an invisible wall" reflected
      this experience. It comprised three categories: (1) declined marital intimacy,
      (2) disarming, and (3) transformation of societal norms into concerns. This study
      proposed new contextual information about the marital relationship of Iranian
      women after surgical menopause that was not openly articulated before and which
      may be applicable for others in such contexts. Women's main concern was the
      emotional separation because of the sexual consequences of the surgery.
      Healthcare providers should be aware of women's concerns, which may alter their
      marital relationship. They must provide individualized care, education, and
      support for couples to make thoughtful decisions about rebuilding their sexual
      relationship. Results may also have implications for psychiatrists, sex/marital
      therapists, and probably clergy who have the authority to openly address this
      important issue to the public.

PMID- 29452056
TI  - Promoting addiction medicine teaching through functional mentoring by co-training
      generalist chief residents with faculty mentors.
AB  - BACKGROUND: Generalist physicians should play a vital role in identifying and
      managing individuals with substance use but are inadequately trained to do so.
      METHODS: This 5-year (2008-2012) controlled educational study assessed whether
      internal medicine and family medicine chief residents' (CRs) addiction medicine
      teaching increased by co-training with faculty mentors at a Chief Resident
      Immersion Training (CRIT) program in addiction medicine. All CRIT CR attendees
      identified a residency program faculty mentor to support addiction medicine
      teaching after CRIT through functional mentoring with a focus on developing and
      implementing an Addiction Medicine Teaching Project ("Teaching Project").
      Approximately half of the CRs attended CRIT with their mentor (co-trained) and
      half without their mentor (solo-trained). Addiction medicine teaching outcomes
      were compared between groups using 6- and 11-month questionnaires and 4 bimonthly
      teaching logs. Of co-trained CRs, mentor characteristics that positively
      influenced addiction medicine teaching outcomes were identified. RESULTS: One
      hundred CRs from 74 residency programs attended CRIT from 2008 to 2012; 47 co
      trained with their mentors and 53 solo-trained without their mentors. At 6-month
      follow-up, the co-trained CRs were more likely to meet at least monthly with
      their mentor (22.7% vs. 9.6%, P < .01) and more likely to identify their mentor
      as a facilitator for Teaching Project implementation (82.2% vs. 38.5%, P < .01).
      At 11-month follow-up, a higher percentage of co-trained CRs had completed their
      Teaching Project (34.0% vs. 15.1%, P < .05). Both CR groups had similarly large
      increases in other addiction medicine teaching outcomes. Mentors with more
      experience, including years of teaching, was associated with better CR Teaching
      Project outcomes. CONCLUSIONS: Co-training generalist chief residents with a
      faculty mentor appeared to facilitate functional mentoring-driven Teaching
      Project implementation but did not further increase already high levels of other
      addiction medicine teaching. Faculty mentors with more years of teaching
      experience were more effective in facilitating Teaching Project implementation.

PMID- 29452057
TI  - Use of Twitter to Assess Viewer Reactions to the Medical Drama, Code Black.
AB  - Fictional medical television programs are popular with viewers and have been
      shown to influence health-related outcomes. We sought to systematically analyze
      real-time viewer discourse on Twitter related to the new medical drama, Code
      Black. We retrieved all Twitter posts (tweets) and metadata around the time of
      the airing of Code Black for four consecutive weeks. We developed a codebook
      using both content assessment of Twitter messages (tweets) and theory-based
      variables used in entertainment education analyses. We coded all tweets that
      occurred during the Eastern Standard Time (EST) airing of the program. Tweets
      that fell into at least one coding category were further analyzed by two
      independent researchers. We collected a total of 19,369 tweets, with 54% of total
      tweets originating during the EST airing of the program. There were 1,888 tweets
      that fit into one or more of six broad coding categories. Qualitative analysis
      revealed several key themes including real-life motivation to pursue health
      sciences careers based on the program, engagement regarding medical accuracy, and
      respect for the nursing profession. Examination of tweets related to Code Black
      provides insight into viewer discourse and suggests that Twitter may provide a
      vehicle for leveraging program engagement into real-life discussion and inquiry.

PMID- 29452058
TI  - A meta-analysis of effectiveness of E-interventions to reduce alcohol consumption
      in college and university students.
AB  - OBJECTIVE: To evaluate the effectiveness and moderators of E-Interventions versus
      assessment only (AO) controls in the reduction of alcoholic drinks per week (DPW)
      in university students. STUDY DESIGN AND METHODS: Cochrane library, CINAEL, ERIC,
      MEDLINE, PsycINFO, PubMed, and Web of Science were searched up to June 2017.
      Studies were included if they were: an RCT, assessed the effectiveness of E
      Interventions at reducing DPW, and employed university/college students. 23
      studies (N = 7,614) were included and quality was assessed using the JADAD scale.
      RESULTS: Weighted mean effect sizes were calculated using random-effects models.
      These showed a small, significant effect of E-Interventions at reducing the
      number of alcoholic DPW. Moderator analysis found a significant advantage for web
      based personalised feedback interventions compared to other E-Interventions.
      CONCLUSIONS: E-Interventions show a small, significant effect at reducing mean
      alcoholic DPW. Personalised feedback E-Interventions showed the strongest effect.

PMID- 29452059
TI  - New Zealand adolescents' concerns about their alcohol use and access to services:
      Associations with ethnicity and other factors.
AB  - Using a national survey of 8,500 New Zealand high school students, we
      investigated adolescents' concerns about their drinking, associated factors
      including help-seeking preferences and access to health care services, and how
      these varied by ethnicity and level of socioeconomic deprivation. Approximately
      23.9% of the 3,704 current drinkers reported concerns (i.e., being worried about
      their drinking and/or having tried to cut down). Regression analyses revealed
      that Maori and Pacific youth were more likely than their New Zealand European
      peers to be concerned about their drinking. Concerned drinkers were more likely
      than nonconcerned drinkers to report hazardous drinking behaviors and alcohol
      related problems, but these associations varied by age, ethnicity, and
      socioeconomic deprivation. Help-seeking preferences differed strongly by
      ethnicity. Concerned drinkers, and Maori and Pacific drinkers, were more likely
      to report difficulties accessing health care and alcohol and drug services. The
      factors associated with adolescents' drinking concerns and paradoxical
      difficulties accessing health care highlight the importance of engaging
      adolescents in developing responsive and equitable services.

PMID- 29452060
TI  - U.S. adolescent alcohol use by race/ethnicity: Consumption and perceived need to
      reduce/stop use.
AB  - Understanding racial/ethnic drinking patterns and service provision preferences
      is critical for deciding how best to use limited alcohol prevention,
      intervention, and treatment resources. We used nationally representative data
      from 150,727 U.S. high school seniors from 2005 to 2016 to examine differences in
      a range of alcohol use behaviors and the felt need to reduce or stop alcohol use
      based on detailed racial/ethnic categories, both before and after controlling for
      key risk/protective factors. Native students reported particularly high use but
      corresponding high felt need to reduce/stop use. White and dual-endorsement
      students reported high use but low felt need to stop/reduce alcohol use.

PMID- 29452061
TI  - What's so appealing? An examination of emotional appeals and viewer engagement in
      safe-sex PSAs and condom advertisements.
AB  - Whereas advertisements strive to increase revenue, PSAs work to educate and
      inform. Even though both share the similar goal of persuasion, advertising tends
      to lead to more effective sales, unlike PSAs, which can have little effect on
      audience behaviors. Using a systematic, quantitative content analysis, this study
      examines emotional appeals and viewer engagement in safe-sex PSAs and condom
      advertisements in online videos (N = 132). PSAs with humor appeals received more
      viewer attention in terms of views, comments, and ratings than humorous
      advertisements. Recommendations for designing public health campaigns are
      discussed in terms of specific appeals for garnering audience attention.

PMID- 29452062
TI  - The Buddy Benefit: Increasing the Effectiveness of an Employee-Targeted Weight
      Loss Program.
AB  - It is well known that significant others (particularly romantic partners) can
      influence people's weight management efforts. However, what constitutes effective
      support-and from which type of individual (e.g., romantic partner, family member,
      friend)-is unclear. Thus, framed by confirmation theory, we assessed the
      effectiveness and types of communication of a weight-loss "buddy" through reports
      of 704 individuals enrolled in a 15-week synchronous online weight-loss program.
      Roughly 54% of participants chose buddies; and those who did lost more weight and
      waist inches than those who were involved in the program without buddy support.
      We also found that a combination of high accepting and high challenging messages
      from buddies was associated with the greatest decrease in body mass index (BMI)
      as well as the greatest reduction in waist size. Furthermore, the support by
      romantic partners paralleled support by other types of buddies. Having a
      supportive buddy who was not a romantic partner was just as effective as turning
      to a romantic partner for assistance. This study underscores the important role
      of a buddy in supporting weight-loss program involvement and encourages
      individuals to consider enlisting the help of a buddy, as opposed to losing
      weight alone, in order to maximize weight management effectiveness.

PMID- 29452063
TI  - Getting Started: An Empirically Derived Logic Model for Age-Friendly Community
      Initiatives in the Early Planning Phase.
AB  - Age-friendly community initiatives (AFCIs) foster efforts across stakeholders to
      make localities more supportive and inclusive of older adults, and potentially
      better for residents of all ages. This study drew on in-depth interviews with
      leaders of nine newly forming AFCIs in northern New Jersey to develop an
      empirically based logic model for the initiatives in the early planning phase.
      The results obtained from a conventional content analysis indicated three main
      activities in the early planning phase: assessing the community; meeting; and
      communicating with stakeholders; and facilitating communitywide communications.
      These activities worked toward two outputs: increased understanding of aging in
      the community and more engaged stakeholders in aging. Participants described
      leveraging the contributions of lead staff, consultants, elected officials,
      organizational partners, volunteers, interns, funders, and other AFCIs to engage
      in their focal activities. Based on these findings, a logic model for AFCIs in
      the early planning phase is presented. AFCI leaders can draw on this model to
      evaluate AFCI processes and outcomes in their formative stages, as well as to
      strategically plan for the start of an AFCI within a given locality. Findings
      also suggest important directions for future research on the development of AFCIs
      and the community changes that they seek to influence.

PMID- 29452064
TI  - College students with congenital heart disease: A critical time for transition.
AB  - : As medical and surgical advances improve, more young adults with congenital
      heart disease (CHD) are attending college. This case study illustrates some of
      the issues that these young adults may face as they attend college and discusses
      the role that college health practitioners can play in easing that transition.
      PARTICIPANTS: A case of a male with CHD presenting to the college health clinic
      with a new onset headache. METHODS: The authors discuss some of the unique
      challenges that college health practitioners may face when caring for students
      with CHD. In addition, they make recommendations on how best to care for these
      patients and how best to coordinate care with CHD students other care providers.
      RESULTS: This student with a history of coarctation of the aorta presented with
      new onset headaches and was found to have high blood pressure. He was diagnosed
      with recurrent coarctation, underwent percutaneous treatment with stenting and
      quickly resumed classes. CONCLUSIONS: As more students with CHD enter college,
      college health providers will need to understand some of the health risks that
      CHD students face. In addition, understanding some of the optimal ways to
      coordinate care with CHD providers can ease the transition that CHD students face
      as they enter college.

PMID- 29452065
TI  - Past-year nonmedical use of prescription drugs among women on probation and
      parole: A cross-sectional study.
AB  - BACKGROUND: Prescription drug-related overdose deaths have increased dramatically
      in recent years. Women in the justice system experience high rates of drug use,
      victimization, trauma symptoms, and other health problems and would appear to be
      at high risk for nonmedical use of prescription drugs (NMUPD). This study will be
      among the first to describe prevalence and correlates of NMUPD among this
      population. METHODS: This cross-sectional study collected data from 406
      victimized women on probation and parole between 2010 and 2012. In a multiple
      logistic regression model, we differentiated women who reported past-year NMUPD
      from those who did not using demographic, health, other drug use, substance use
      treatment, and trauma symptom severity variables. RESULTS: Past-year NMUPD was
      reported by 26.8% (n = 109) of the overall sample. Women reporting NMUPD were
      significantly younger and more likely to be white. Past-year use of alcohol
      (adjusted odds ratio [AOR]: 3.3; 95% confidence interval [CI]: 1.8-6.1),
      marijuana (AOR: 3.6; 95% CI: 1.8-7.0), methamphetamines (AOR: 6.1; 95% CI: 1.7
      21.3), and heroin (AOR: 8.4; 95% CI: 2.0-35.2) were significantly associated with
      NMUPD. Additionally, each unit increase in the measure assessing bodily pain was
      associated with a 40% increase (AOR: 1.4; 95% CI: 1.1-1.7) in the odds of NMUPD.
      Finally, meeting diagnostic criteria for posttraumatic stress disorder almost
      doubled (AOR: 1.9; 95% CI: 1.1-3.4) the odds of reporting past-year NMUPD.
      CONCLUSIONS: Victimized women on probation and parole report high rates of NMUPD,
      and this behavior intersects with other complex social, behavioral,
      psychological, and physical needs. The authors recommend increased access to
      trauma-informed correctional care among women in the justice system.

PMID- 29452066
TI  - Biopsychosocial factors: Antecedent and consequential to women's health issues.

PMID- 29452067
TI  - Alcohol and drug use among deaf and hard-of-hearing individuals: A secondary
      analysis of NHANES 2013-2014.
AB  - BACKGROUND: Within the field of behavioral health research, one of the most
      understudied populations is the US deaf and hard-of-hearing (D/HH) population-a
      diverse group of individuals with hearing loss that have varied language and
      communication preferences, community affiliations, and sociocultural norms.
      Recent research identified concerning behavioral health disparities experienced
      by the D/HH population; yet, little research has been conducted to extend these
      findings to the topic of substance use disorder. METHODS: To begin to fill this
      gap, the authors conducted a secondary analysis of data from the 2013-2014
      administration of the National Health and Nutrition Examination Survey, comparing
      alcohol and drug use between participants based on their reported hearing status,
      i.e., D/HH or hearing. RESULTS: Findings suggest that the overall lifetime
      prevalence of alcohol and drug use does not differ based on hearing status, and
      that D/HH and hearing adolescents begin using cannabis on a similar timeline.
      However, findings also revealed that D/HH respondents were more likely to have
      been regular cannabis users and heavy alcohol users than hearing respondents. In
      other words, when D/HH individuals use substances, they tend to be heavy users.
      CONCLUSIONS: These findings stress the importance of directing resources to the
      prevention and treatment of heavy alcohol use in the D/HH population, given that
      binge drinking is associated with a number of health problems and social
      consequences. Additionally, the continuation of this empirical work is rather
      urgent given recent legislative changes regarding cannabis use. D/HH individuals
      possess a number of risk factors for substance use disorder and, as such, may be
      more greatly impacted by these legislative changes than individuals from the
      general US population. It is imperative that this impact be captured by future
      research efforts in order to inform the development of prevention and
      intervention efforts for the traditionally underserved D/HH population.

PMID- 29452068
TI  - Glycyrrhizin attenuates histamine-mediated MUC5AC upregulation, inflammatory
      cytokine production, and aquaporin 5 downregulation through suppressing the NF
      kappaB pathway in human nasal epithelial cells.
AB  - Allergic rhinitis (AR) is a chronic respiratory inflammatory disease.
      Glycyrrhizin is a main bioactive component of the licorice root extract and
      exhibits anti-inflammatory activity. However, the role of glycyrrhizin in AR has
      not been studied. The aim of the present study was to investigate the effect of
      glycyrrhizin on histamine-induced human nasal epithelial cells (HNEpCs). Here, we
      found that glycyrrhizin (20 or 40 MUM) inhibited histamine-induced the mRNA
      expression and secretion of mucin 5 subtype AC (MUC5AC), interleukin (IL)-6 and
      IL-8 in HNEpCs. The expression levels of aquaporin 5 (AQP5) and phosphorylated
      cyclic adenosine monophosphate-responsive element binding protein (p-CREB) were
      decreased by histamine in HNEpCs and increased in cells treated with
      glycyrrhizin. The glycyrrhizin treatment inhibited histamine-induced expressions
      of p-NF-kappaB p65 and p-IkappaBalpha in HNEpCs, indicating that glycyrrhizin
      inhibited the activation of NF-kappaB pathway in histamine-induced HNEpCs. In
      addition, inhibition of the NF-kappaB pathway exhibited the similar effect with
      glycyrrhizin on histamine-induced HNEpCs. In summary, the results showed that
      glycyrrhizin reversed the effect of histamine on MUC5AC expression, inflammatory
      cytokine production, and AQP5 expression in HNEpCs, and the NF-kappaB pathway was
      involved in the effect. Glycyrrhizin might be used for complementary and
      alternative therapeutics of AR.

PMID- 29452069
TI  - Idiopathic Isolated Unilateral Hypoglossal Nerve Palsy: A Report of 2 Cases and
      Review of the Literature.
AB  - Hypoglossal nerve palsy (HNP) is a common finding in neurologic diseases when
      associated with other cranial nerve palsies or further pathology and exhibits
      characteristic clinical manifestations, including unilateral atrophy of the
      musculature of the tongue. It occasionally appears as the initial or solitary
      sign of an intracranial or extracranial space-occupying lesion, head or neck
      injury, or vascular abnormality of the internal carotid artery. There are few
      cases of idiopathic isolated unilateral HNP, which should be diagnosed through
      exclusion. This report describes 2 patients who had different outcomes and
      presents a literature review of idiopathic isolated unilateral HNP. Case 1 was a
      71-year-old man who was referred with a 1-month history of dysphagia and speech
      impairment. Intraoral examination disclosed marked left-side hemiatrophy of the
      tongue and deviation toward the left on protrusion. At coronal Tl-weighted
      magnetic resonance imaging, left-side hemiatrophy of the tongue was clearly
      visible through deviation of the median septum to the left. The patient was
      diagnosed with idiopathic isolated unilateral HNP through exclusion and was
      treated with steroids and mecobalamin, but he did not recover. Case 2 was a 32
      year-old man complaining of tongue weakness for 2 days. On examination, left HNP
      was evident, with deviation of the tongue to the left on protrusion. He was
      diagnosed with idiopathic isolated unilateral HNP through exclusion and was
      treated with steroids. After 3 weeks, the patient had completely recovered. To
      the best of the authors' knowledge, this is the first detailed literature review
      on idiopathic isolated unilateral HNP. This condition is very rare but should be
      considered for diagnosis. It warrants a thorough and stepwise approach for
      etiologic diagnosis.

PMID- 29452070
TI  - A Modified Peri-Angular Approach for Exposure of Condylar Fractures.
AB  - PURPOSE: To describe a modified peri-angular approach to address subcondylar and
      condylar neck fractures. MATERIALS AND METHODS: A modified peri-angular incision
      is used to approach a fractured condyle through the anteroparotid transmasseteric
      approach. RESULTS: In the authors' experience, this method provides quick and
      clean exposure to the fractured condylar base and neck fractures for open
      reduction and internal fixation. CONCLUSION: Although the peri-angular approach
      has been discussed in the literature, the authors' modification lessens the
      chance of complications, such as marginal nerve injury and parotid fistula
      formation, because the nerve is visualized and kept isolated throughout.

PMID- 29452072
TI  - Pacifier and bottle nipples: the targets for poor breastfeeding outcomes.

PMID- 29452071
TI  - CaMKII inhibition ameliorated levodopa-induced dyskinesia by downregulating
      tyrosine hydroxylase activity in an experimental model of Parkinson's disease.
AB  - Levodopa (L-dopa) remains the best treatment for Parkinson's disease (PD).
      However, long-term L-dopa treatment induces dyskinesia. The mechanism of L-dopa
      induced dyskinesia (LID) is not fully understood. Enhanced activity of protein
      kinase A (PKA) and pulsatile dopamine (DA) stimulation plays an important role in
      LID. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for DA synthesis.
      Decreased TH activity causes reduced pulsatile DA stimulation, which in turn
      reduces LID. Moreover, TH is a substrate of CaMKII. However, it is unknown
      whether inhibition of CaMKII reduces LID by downregulating the activity of TH. In
      this study, we found that CaMKII antagonist KN-93 reduced DA released in PC12
      cells; in the meantime, KN-93 reduced phosphorylated levels of CaMKIIalpha and TH
      at Ser 40. Intrastriatal administration of KN-93 reduced LID without affecting
      the antiparkinsonian effect of L-dopa in PD mice. Mechanistically, KN-93
      treatmentreduced phosphorylated CaMKIIalpha levels and subsequently downregulated
      phosphorylated TH at Ser 40 expression. Consequently, extracellular DA efflux was
      reduced andthe activation threshold of the PKA pathway was lowered. Moreover, KN
      93 treatment reduced the expression of Arc and Penk, two immediate early genes,
      induced by chronic L-dopa. These data indicate that inhibition of CaMKIIalpha
      decreases LID at least partially by suppressing TH activity and subsequently
      reducing extracellular DA efflux and the activity of the PKA pathway, suggesting
      that CaMKIIalpha may be an alternative target for the treatment of LID.

PMID- 29452073
TI  - The role of adiponectin and adipolin as anti-inflammatory adipokines in the
      formation of macrophage foam cells and their association with cardiovascular
      diseases.
AB  - Obesity is one of the major public health concerns that is closely associated
      with obesity-related disorders such as type 2 diabetes mellitus (T2DM),
      hypertension, and atherosclerosis. Atherosclerosis is a chronic disease
      characterized by excess cholesterol deposition in the arterial intima and the
      formation of foam cells. Adipocytokines or adipokines are secreted by the adipose
      tissue as endocrine glands; adiponectin and adipolin are among these adipokines
      that are associated with obese and insulin-resistant phenotypes. Adipolin and
      adiponectin are cytokines that exert substantial impact on obesity, progression
      of atherosclerosis, insulin resistance, and glucose metabolism. In this paper, we
      review the formation of macrophage foam cells, which are associated with
      atherosclerosis, and the macrophage mechanism, which includes uptake,
      esterification, and release. We also summarize current information on adipose
      tissue-derived hormone and energy homeostasis in obesity. Finally, the role of
      adipokines, e.g., adipoline and adiponectin, in regulating metabolic,
      cardiovascular diseases is discussed.

PMID- 29452075
TI  - Physiological correlates of reproductive decisions: Relationships among body
      condition, reproductive status, and the hypothalamus-pituitary-adrenal axis in a
      reptile.
AB  - When opportunities to feed and reproduce are limited, females are often unable to
      recover sufficient energy stores to reproduce in consecutive years. Body
      condition has been used as a proxy for recent reproductive history in such
      species. We previously found that glucocorticoid responses to capture stress vary
      with body condition in female red-sided garter snakes (Thamnophis sirtalis
      parietalis), a species with limited seasonal breeding opportunities. Because
      variation in glucocorticoid receptor (GR) protein in the brain could explain
      these differences, we first assessed GR protein content in females in different
      body conditions. To investigate if body condition during the spring mating season
      accurately reflects recent reproductive history, we measured glucocorticoid
      responses to stress in females with different body conditions, assessed their
      mating behavior and brought mated females to our lab to determine which females
      would give birth during the summer (i.e., were parturient). Female red-sided
      garter snakes reproduce biennially, and therefore mated females that did not give
      birth were deemed non-parturient. In this study, glucocorticoid stress responses
      and mating behavior did not vary with body condition, nor was body condition
      related to brain GR or reproductive condition (parturient vs non-parturient).
      Only unreceptive females showed a significant stress-induced increase in
      glucocorticoids, suggesting that reduced stress responsiveness is associated with
      receptivity. Parturient females mated faster (were more proceptive) than non
      parturient females. These data suggest that HPA axis activity modulates
      receptivity, while proceptivity is related primarily to reproductive condition.

PMID- 29452076
TI  - Feasibility of EUS-guided Nd:YAG laser ablation of unresectable pancreatic
      adenocarcinoma.
AB  - BACKGROUND AND AIMS: EUS has become an interventional technique in which a needle
      may be used as a vehicle to deliver therapeutic agents. Laser ablation (LA) has
      been used to treat many primary and secondary neoplasms. This study aimed to
      assess the feasibility of EUS-guided LA for unresectable (UR) pancreatic cancer.
      METHODS: Patients with stage IIb-III pancreatic cancer underwent EUS-guided LA.
      All patients were unresponsive to previous chemoradiotherapy. LA was performed by
      using a 300-MUm flexible fiber preloaded onto a 22-gauge fine needle. A 1064-nm
      wavelength neodymium-yttrium aluminum garnet (Nd:YAG) laser light with different
      power settings of 2 W for 800 J, 1000 J, and 1200 J; 3 W for 800 J, 1000 J, and
      1200 J; and 4 W for 800 J, 1000 J, and 1200 J was used. Each patient was treated
      with a single application of 1 of these settings. The application time of the
      power settings ranged from 200 to 600 seconds. RESULTS: Nine patients (median
      age, 74.7; range 55-85) underwent Nd:Yag LA. The mean size of the focal lesion
      was 35.4 mm (range, 21-45). The ablation area, demonstrated by 24-hour CT, ranged
      from .4 cm3 (for the lower power setting of 2 W/800 J) to a maximum of 6.4 cm3
      (for 4 W/1000 J). The procedure was completed in all 9 patients without adverse
      events. CONCLUSION: In our human experience, EUS-guided LA was feasible and well
      tolerated in patients with UR pancreatic cancer.

PMID- 29452074
TI  - Differential control of appetitive and consummatory sexual behavior by
      neuroestrogens in male quail.
AB  - Contribution to Special Issue on Fast effects of steroids. Estrogens exert
      pleiotropic effects on multiple physiological and behavioral traits including
      sexual behavior. These effects are classically mediated via binding to nuclear
      receptors and subsequent regulation of target gene transcription. Estrogens also
      affect neuronal activity and cell-signaling pathways via faster, membrane
      initiated events. Although the distinction between appetitive and consummatory
      aspects of sexual behavior has been criticized, this distinction remains valuable
      in that it facilitates the causal analysis of certain behavioral systems. Effects
      of neuroestrogens produced by neuronal aromatization of testosterone on
      copulatory performance (consummatory aspect) and on sexual motivation (appetitive
      aspect) are described in male quail. The central administration of estradiol
      rapidly increases expression of sexual motivation, as assessed by two measures of
      sexual motivation produced in response to the visual presentation of a female but
      not sexual performance in male Japanese quail. This effect is mimicked by
      membrane-impermeable analogs of estradiol, indicating that it is initiated at the
      cell membrane. Conversely, blocking the action of estrogens or their synthesis by
      a single intracerebroventricular injection of estrogen receptor antagonists or
      aromatase inhibitors, respectively, decreases sexual motivation within minutes
      without affecting performance. The same steroid has thus evolved complementary
      mechanisms to regulate different behavioral components (motivation vs.
      performance) in distinct temporal domains (long- vs. short-term) so that diverse
      reproductive activities can be properly coordinated. Changes in preoptic
      aromatase activity and estradiol as well as glutamate concentrations are observed
      during or immediately after copulation. The interaction between these
      neuroendocrine/neurochemical changes and their functional significance is
      discussed.

PMID- 29452078
TI  - Ice-free cryopreservation of heart valve tissue: The effect of adding MitoQ to a
      VS83 formulation and its influence on mitochondrial dynamics.

PMID- 29452077
TI  - Clinical outcomes and factors related to colonic perforations in patients
      receiving self-expandable metal stent insertion for malignant colorectal
      obstruction.
AB  - BACKGROUND AND AIMS: Although colonic perforation is a dreadful adverse event
      associated with stent placement, data on this topic are sparse. We aimed to
      investigate the clinical outcomes of colonic perforation and factors related to
      its occurrence in patients who received self-expandable metal stents (SEMSs) for
      malignant colorectal obstruction. METHODS: We retrospectively reviewed the data
      of 474 patients with malignant colorectal obstruction who received endoscopic
      SEMS insertion from April 2004 to May 2011 in Severance Hospital and Gangnam
      Severance Hospital. Early perforation, defined as perforation occurring within 2
      weeks, was assessed in bridge-to-surgery (n = 164) and palliative stent placement
      patient groups (n = 310). Delayed perforation was analyzed using data from the
      palliative stent placement group alone. RESULTS: The technical and clinical
      success rates were 90.5% and 81.0%, respectively. Early and delayed perforations
      occurred in 2.7% (13/474) and 2.7% (8/301) of patients, respectively. Among 21
      patients with perforation, 14 (66.7%) received emergency surgery and 5 (23.8%)
      died within 30 days after perforation. Regarding the perforation-related factors,
      age >=70 years (odds ratio, 3.276; 95% confidence interval [CI], 1.041-10.309)
      and sigmoid colonic location (odds ratio, 7.706; 95% CI, 1.681-35.317) were
      independently associated with occurrence of early perforation. Stent location in
      the flexure (hazard ratio, 17.573; 95% CI, 2.004-154.093) and absence of
      peritoneal carcinomatosis (hazard ratio, 6.139; 95% CI, 1.150-32.776) were
      significantly associated with delayed perforation. CONCLUSIONS: The perforation
      related 30-day mortality rate was 23.8%. Older age and sigmoid colonic location
      were significantly associated with occurrence of early perforation, whereas
      flexure location and absence of peritoneal carcinomatosis were related to delayed
      perforation.

PMID- 29452079
TI  - Case report: Retroperitoneal bronchogenic cyst as a diagnostic dilemma after
      colon cancer diagnosis.
AB  - A 52 year-old obese male presented with a moderately differentiated
      adenocarcinoma of the sigmoid colon. On staging CT, the patient was found to have
      a cystic lesion in the left retroperitoneum.

PMID- 29452080
TI  - An unusual presentation of primary pulmonary extranodal marginal zone lymphoma of
      mucosal associated lymphoid tissue: An autopsy case report.
AB  - A 40 year old female with no documented medical history presented to the
      Emergency Department with several days of lethargy and altered mental status. She
      was found to be anemic, thrombocytopenic, and hypotensive. The patient was found
      to be in severe metabolic acidosis, became bradycardic, and quickly deteriorated.
      Clinicians suspected thrombotic thrombocytopenic purpura, and the diagnosis was
      supported by ADAMTS13 testing. The clinicians attempted to place a Quinton
      catheter for emergent plasmapheresis, but the patient expired before definitive
      treatment could be initiated. Autopsy was obtained and revealed a right middle
      lobe consolidation grossly consistent with lymphoid tissue or tumor.

PMID- 29452081
TI  - Chronic Nosema ceranae infection inflicts comprehensive and persistent
      immunosuppression and accelerated lipid loss in host Apis mellifera honey bees.
AB  - Nosema ceranae is an intracellular microsporidian parasite of the Asian honey bee
      Apis cerana and the European honey bee Apis mellifera. Until relatively recently,
      A. mellifera honey bees were naive to N. ceranae infection. Symptoms of
      nosemosis, or Nosema disease, in the infected hosts include immunosuppression,
      damage to gut epithelium, nutrient and energetic stress, precocious foraging and
      reduced longevity of infected bees. Links remain unclear between
      immunosuppression, the symptoms of nutrient and energetic stress, and precocious
      foraging behavior of hosts. To clarify physiological connections, we inoculated
      newly emerged A. mellifera adult workers with N. ceranae spores, and over 21 days
      post inoculation (21 days pi), gauged infection intensity and quantified
      expression of genes representing two innate immune pathways, Toll and Imd.
      Additionally, we measured each host's whole-body protein, lipids, carbohydrates
      and quantified respirometric and activity levels. Results show sustained
      suppression of genes of both humorally regulated immune response pathways after 6
      days pi. At 7 days pi, elevated protein levels of infected bees may reflect
      synthesis of antimicrobial peptides from an initial immune response, but the lack
      of protein gain compared with uninfected bees at 14 days pi may represent low de
      novo protein synthesis. Carbohydrate data do not indicate that hosts experience
      severe metabolic stress related to this nutrient. At 14 days pi infected honey
      bees show high respirometric and activity levels, and corresponding lipid loss,
      suggesting lipids may be used as fuel for increased metabolic demands resulting
      from infection. Accelerated lipid loss during nurse honey bee behavioral
      development can have cascading effects on downstream physiology that may lead to
      precocious foraging, which is a major factor driving colony collapse.

PMID- 29452082
TI  - Pre-treatment red blood cell distribution width provides prognostic information
      in multiple myeloma.
AB  - BACKGROUND: The red blood cell distribution width (RDW), a credible marker for
      abnormal erythropoiesis, has recently been studied as a prognostic factor in
      oncology, but its role in multiple myeloma (MM) hasn't been thoroughly
      investigated. METHODS: We performed a retrospective study in 162 patients with
      multiple myeloma. Categorical parameters were analyzed using Pearson chi-squared
      test. The Mann-Whitney and Wilcoxon tests were used for group comparisons.
      Comparisons of repeated samples data were analyzed with the general linear model
      repeated-measures procedure. The Kaplan-Meier product-limit method was used to
      determine OS and PFS, and the differences were assessed by the log-rank test.
      RESULTS: High RDW baseline was significantly associated with indexes including
      haemoglobin, bone marrow plasma cell infiltration, and cytogenetics risk
      stratification. After chemotherapy, the overall response rate (ORR) decreased as
      RDW baseline increased. In 24 patients with high RDW baseline, it was revealed
      RDW value decreased when patients achieved complete remission (CR), but increased
      when the disease progressed. The normal-RDW baseline group showed both longer
      overall survival (OS) and progression-free survival (PFS) than the high-RDW
      baseline group. CONCLUSION: Our study suggests pre-treatment RDW level is a
      prognostic factor in MM and should be regarded as an important parameter for
      assessment of therapeutic efficiency.

PMID- 29452083
TI  - Tribolium castaneum gene expression changes after Paranosema whitei infection.
AB  - BACKGROUND: Microsporidia are obligate parasites that possess some of the
      smallest eukaryotic genomes. Several insect species are susceptible to infections
      by microsporidian parasites. Paranosema whitei frequently infects young larvae of
      Tribolium castaneum and obligately kills the host whereupon transmission to
      subsequent hosts is accomplished via spores. P. whitei infection results in
      developmental arrest of T. castaneum, preventing larvae from pupation. The
      mechanisms underlying P. whitei virulence as well as the molecular underpinning
      of host defenses remain uncharacterized. In the present study, we evaluated gene
      expression differences of T. castaneum infected with the microsporidian parasite
      P. whitei. RESULTS: More than 1500 T. castaneum genes were differentially
      expressed after infection with P. whitei. Several important host pathways
      appeared to be differentially expressed after infection, where immune genes were
      among the highest differential expressed genes. Genes involved in the Toll
      pathway and its effectors were specifically upregulated. Furthermore, iron
      homeostasis processes and transmembrane transport appeared significantly altered
      after P. whitei infection. Kruppel homolog 1 (Kr-h1) and other genes of the
      juvenile hormone (JH) pathway appeared differentially expressed after parasite
      infection. In addition, a small number of long intergenic non-coding RNAs
      (lincRNAs) appeared differentially expressed after P. whitei infection.
      CONCLUSION: In this study we characterized for the first time using RNA-seq the
      immune response of T. castaneum to P. whitei. Other pathways (transmembrane
      transport, iron homeostasis, protein synthesis, JH) indicate possible alterations
      of the host by the parasite such as a possible developmental arrest caused by JH
      regulation. Furthermore we find evidence that some lincRNAs might be connected to
      defense as previously reported for other insect species.

PMID- 29452084
TI  - Successful reproduction of unmated Tropilaelaps mercedesae and its implication on
      mite population growth in Apis mellifera colonies.
AB  - Successful reproduction by unmated Tropilaelaps mercedesae is reported here for
      the first time. Of the eight mature daughters that did not have male mates within
      their natal cells, four produced both mature sons and daughters, and four
      produced mature daughters only. Overall, 78% of the new daughters that had no egg
      laying experience, and 84% of the foundresses that had or had not laid previously
      reproduced. Both inoculum daughter and foundress mites were collected from tan
      bodied pupae and inoculated immediately. Therefore, our results suggest that
      phoresy is not required for reproduction in tropilaelaps mites. The ability of
      virgin females to lay both males and females (deuterotoky), and to reproduce
      without spending a phoretic period on adult bees may play major roles in
      tropilaelaps mites' competitive advantage over varroa mites in Apis mellifera
      colonies.

PMID- 29452085
TI  - Preface: Regional status of microbial control programs.

PMID- 29452086
TI  - Ameliorative effects of clonidine on ethanol induced kidney injury in rats:
      Potential role for imidazoline-1 receptor.
AB  - Chronic alcoholism is a risk factor for kidney injury. Clonidine is an alpha2
      adrenergic receptor/imidazoline-1 receptor agonist that can reduce blood pressure
      and maintain renal functions. This study aims to investigate the possible
      ameliorative effects of clonidine on ethanol induced kidney injury and its
      mechanism of action. Kidney injury was induced in rats by adding ethanol to
      drinking water for eight weeks. Clonidine effects on kidney functions and
      histopathology were measured. Moreover, phentolamine (alpha-adrenergic receptor
      antagonist), efaroxan (imidazoline-1 receptor antagonist) and rilmenidine
      (imidazoline-1 receptor agonist) were used to clarify the role of imidazoline-1
      receptor in mediating renal ameliorative effects. Also, the effect of clonidine
      on liver functions and metabolic changes, in addition to renal oxidative stress,
      inflammatory and apoptotic pathways were measured. Results showed that, clonidine
      improved renal functions and reduced ethanol induced renal inflammation and
      fibrosis. On the other hand, efaroxan, only, blocked clonidine effects on kidney
      functions. Rilmenidine decreased kidney injury like clonidine. Both clonidine and
      rilmenidine increased renal nischarin gene expression. Furthermore, clonidine
      improved liver functions, increased serum insulin and decreased serum advanced
      glycation end products (metabolic markers). Also, clonidine reduced renal
      oxidative stress as reflected by decreased myeloperoxidase, malondialdehyde,
      inducible nitric oxide synthase and total nitric oxide levels and increased
      superoxide dismutase level. Moreover, clonidine reduced renal tumor necrosis
      factor-alpha (inflammatory marker) and caspase-3 (apoptotic marker) levels, while
      increased renal prostaglandine E2 and interleukin-10 levels (anti-inflammatory
      markers). In conclusion, clonidine can reduce ethanol induced kidney injury, at
      least in part, by stimulating imidazoline-1 receptor signaling.

PMID- 29452087
TI  - PNPLA3: A Determinant of Response to Low-Fructose Diet in Nonalcoholic Fatty
      Liver Disease.

PMID- 29452088
TI  - Proton Pump Inhibitors and Chronic Kidney Disease: Is It Related to the
      Accumulation of Toxic Breakdown Products Spontaneously Formed in the Enteric
      Protected Tablets?

PMID- 29452089
TI  - Rethinking Reprocessing: A Response to Snyder et al.

PMID- 29452090
TI  - Activation of calcium-sensing receptor-mediated autophagy in angiotensinII
      induced cardiac fibrosis in vitro.
AB  - Cardiac fibrosis is one of the primary mechanisms of ventricular remodeling, and
      there is no effective method for reversal. Activation of calcium sensing receptor
      (CaSR) has been reported to be involved in the development of myocardial
      fibrosis, but the molecular mechanism for CaSR activation has not yet been
      clarified and needs to be further explored. Here, we found that AngII induces
      cardiac fibroblast proliferation and phenotypic transformation in a dose
      dependent manner with increased CaSR and autophagy related protein (Beclin1,
      LC3B) expression. CaSR activation results in intracellular calcium release,
      MEK1/2 pathway phosphorylation, autophagy activation and collagen formation
      induced by AngII in cardiac fibroblasts. However, pretreating the cells with
      Calhex231, PD98059 or 3-MA partially blocked AngII-induced cardiac fibrosis. Our
      data indicate that the activation of CaSR-mediated MEK/ERK and autophagic
      pathways is involved in AngII-induced cardiac fibrosis in vitro.

PMID- 29452091
TI  - Expression profiles and clinical value of plasma exosomal Tim-3 and Galectin-9 in
      non-small cell lung cancer.
AB  - Exosomes are membrane-bound, virus-sized vesicles present in circulating blood.
      Tumor cells are avid producers of exosomes, which are thought to mimic molecular
      features of parent tumor cells. T-cell immunoglobulin- and mucin-domain
      containing molecule 3 (Tim-3) is a the next-generation immune checkpoint that can
      be activated by its ligand Galectin-9 to negatively regulate the anti-tumor
      immune response. However, the characteristics of plasma exosomal Tim-3 and
      Galectin-9 (Exo-T/G) in cancer remained unknown. This study was conducted to
      investigate the expression patterns and clinical value of plasma exosomal total
      protein (Exo-pro) and Exo-T/G in non-small cell lung cancer (NSCLC). Plasma was
      collected from 103 NSCLC patients including 60 early stages and 43 advanced
      stages disease samples as well as 56 healthy subjects. Exosomes were isolated
      from plasma by commercial exosome precipitation solution and identified by
      western blotting of CD63 and transmission electron microscopy. Exo-pro
      concentration was measured by the BCA assay. Enzyme-linked immunosorbent assay
      was used to quantify Exo-T/G. Additionally, 34 NSCLC samples were applied to
      directly detect plasma TIM-3 (Plas-T) and Galectin-9 (Plas-G). Our results showed
      that Exo-pro, Exo-T, and Exo-G were significantly increased in NSCLC plasma
      compared to that in the healthy samples. High levels of Exo-T and Exo-G were all
      positively correlated with several malignant parameters, including larger tumor
      size, advanced stages, and more distant metastasis. High levels of Exo-pro and
      Exo-T were also correlated with more lymph node metastasis. Additionally, plasma
      from lung squamous cell carcinoma showed higher Exo-T and Exo-G compared with
      that from lung adenocarcinoma. ALK-positive patients showed to have decreased Exo
      T and Exo-G levels. Pearson's correlation analysis revealed a significant
      correlation between Exo-pro and Exo-T/G, Exo-T and Exo-G, Exo-T and Plas-T, Exo-G
      and Plas-G, and Plas-T and Plas-G. Together, our data revealed that Exo-pro,
      especially Exo-T and Exo-G could be potential biomarkers for NSCLC. Further
      studies focusing on pure tumor-derived exosomes isolated from plasma were needed.

PMID- 29452092
TI  - MicroRNA-630 inhibitor sensitizes chemoresistant ovarian cancer to chemotherapy
      by enhancing apoptosis.
AB  - MicroRNA-630 (miR-630) has been implicated in the development and progression of
      multiple cancers. The current study aimed to investigate the role of miR-630 in
      chemoresistant epithelial ovarian cancer. MiR-630 expression levels were detected
      in ovarian cancer cell line SKOV3 and paclitaxel-resistant SKOV3 (SKOV3-TR) via
      microarray and qRT-PCR. MiR-630 inhibitors and negative controls were transfected
      into SKOV3 and SKOV3-TR cells. Wound healing, invasion, chemosensitivity, and
      cell apoptosis assays were performed to determine proliferation and migration
      rates. Chemoresistant patient-derived xenograft (PDX) models were established and
      utilized to verify the effect of miR-630 on chemoresistant ovarian cancer.
      Inhibition of miR-630 decreased cell proliferation and enhanced the sensitivity
      of SKOV3-TR and SKOV3 cells to paclitaxel. In the chemosensitivity assay, we
      observed that the miR-630 inhibitor exhibited a synergistic effect with
      paclitaxel on SKOV3-TR cells. Inhibition was correlated with enhanced expression
      of apoptosis-related proteins. APAF-1 was predicted to be a potential target of
      miR-630. An in vivo PDX study showed that the miR-630 inhibitor sensitized
      chemoresistant ovarian cancer to paclitaxel. Thus, miR-630 inhibitor sensitizes
      chemoresistant epithelial ovarian cancer to chemotherapy by enhancing apoptosis.
      Our findings suggest that miR-630 might be a potential therapeutic target for
      chemotherapy-resistant ovarian cancer.

PMID- 29452093
TI  - Autophagy inhibition enhances anticancer efficacy of artepillin C, a cinnamic
      acid derivative in Brazilian green propolis.
AB  - Propolis, a resinous substance produced by honeybees, possesses various
      biological actions including anticancer activity towards tumor cells. Recently,
      the ethanol extract of Brazilian green propolis has been shown to induce
      autophagy, which is known to be induced in treatment of cancer cells with
      anticancer drugs, leading to cancer cell survival and decreased sensitivity to
      anticancer agents. In this study, we aimed to identify autophagy-inducing
      components of the propolis and elucidated the reciprocal relationship between
      anticancer cytotoxicity and protective autophagy in prostate cancer CWR22Rv1
      cells. Among eight cinnamic acid derivatives [chlorogenic acid, p-coumaric acid,
      caffeic acid, 3,4-caffeoylquinic acid, artepillin C (ArtC), baccharin, drupanin
      and caffeic acid phenethyl ester] in propolis, only ArtC showed high autophagy
      inducing activity accompanying LC3-II upregulation. ArtC was also induced
      apoptosis as revealed by DNA fragmentation and increases in cleaved caspase-3 and
      poly ADP-ribose polymerase. The apoptosis induced by ArtC was exacerbated by
      cotreatment with autophagy inhibitors (chloroquine, wortmannin and U0126). The
      cotreatment further induced necroptosis accompanying increased expression of
      receptor-interacting serine/threonine protein kinases 1 and 3. These data
      indicate that cytotoxicity of ArtC to the prostate cancer cells is dampened by
      induced autophagy, but is markedly augmented by inhibition of autophagy.
      Therefore, the combination of ArtC and autophagy inhibitors may be a novel
      complementary-alternative treatment for prostate cancer.

PMID- 29452096
TI  - The macrophage heme-heme oxygenase-1 system and its role in inflammation.
AB  - Heme oxygenase (HO)-1, the inducible isoform of the heme-degrading enzyme HO,
      plays a critical role in inflammation and iron homeostasis. Regulatory functions
      of HO-1 are mediated via the catalytic breakdown of heme, which is an iron
      containing tetrapyrrole complex with potential pro-oxidant and pro-inflammatory
      effects. In addition, the HO reaction produces the antioxidant and anti
      inflammatory compounds carbon monoxide (CO) and biliverdin, subsequently
      converted into bilirubin, along with iron, which is reutilized for
      erythropoiesis. HO-1 is up-regulated by a plethora of stimuli and injuries in
      most cell types and tissues and provides salutary effects by restoring
      physiological homeostasis. Notably, HO-1 exhibits critical immuno-modulatory
      functions in macrophages, which are a major cell population of the mononuclear
      phagocyte system. Macrophages play key roles as sentinels and regulators of the
      immune system and HO-1 in these cells appears to be of critical importance for
      driving resolution of inflammatory responses. In this review, the complex
      functions and regulatory mechanisms of HO-1 in macrophages will be high-lighted.
      A particular focus will be the intricate interactions of HO-1 with its substrate
      heme, which play a contradictory role in distinct physiological and
      pathophysiological settings. The therapeutic potential of targeted modulation of
      the macrophage heme-HO-1 system will be discussed in the context of inflammatory
      disorders.

PMID- 29452095
TI  - The role of free-fatty acid receptor-4 (FFA4) in human cancers and cancer cell
      lines.
AB  - A dietary influence on cancer progression has been evident for many decades, and
      dietary fatty acids, particularly long chain mono- and polyunsaturated fatty
      acids, have been shown to play significant roles in influencing growth of a
      variety of human cancers. The discovery of the family of cell-surface free-fatty
      acid receptors, which include the long-chain fatty acid receptors FFA1 and FFA4,
      suggest that many of the effects of dietary fats could be receptor-mediated. FFA4
      is ubiquitously expressed and has recently been shown to modulate a variety of
      important anti-inflammatory and metabolic processes. Since FFA4 is currently an
      attractive drug target for treatment of metabolic disorders such as diabetes and
      obesity, understanding its role in cancer progression is critical towards the
      drug discovery process. In this research update, the current body of knowledge on
      the role of this receptor in regulating cancer cell proliferation, migration, and
      invasion, as well as in vivo tumorigenesis is reviewed.

PMID- 29452097
TI  - Stimulation of TRPV1 channels activates the AP-1 transcription factor.
AB  - Transient receptor potential vanilloid 1 (TRPV1) channels were originally
      described as the receptors of capsaicin, the main constituent of hot chili
      pepper. The biological functions of TRPV1 channels include pain sensation and
      inflammatory thermal hyperalgesia. Here, we show that stimulation of HEK293 cells
      expressing TRPV1 channels (H2C1 cells) with capsaicin or the TRPV1 ligand
      resiniferatoxin activated transcription mediated by the transcription factor AP
      1. No cell death was occurring under these experimental conditions. The AP-1
      activity was not altered in capsaicin or resiniferatoxin-stimulated HEK293 cells
      lacking TRPV1. We identified the AP-1 DNA binding site as the
      capsaicin/resiniferatoxin-responsive element. Stimulation with the TRPV1 ligand N
      arachidonoyldopamine increased AP-1 activity in a TRPV1-dependent and TRPV1
      independent manner. Stimulation of TRPV1 channels induced an influx of Ca2+ into
      the cells and this rise in intracellular Ca2+ was essential for activating AP-1
      in capsaicin or resiniferatoxin-stimulated cells. N-arachidonoyldopamine
      stimulation induced a rise in intracellular Ca2+ in a TRPV-1 dependent and
      independent manner. AP-1 is a dimeric transcription factor, composed of proteins
      of the c-Jun, c-Fos and ATF families. Stimulation of TRPV1 channels with
      capsaicin increased c-Jun and c-Fos biosynthesis in H2C1 cells. The signal
      transduction of capsaicin, leading to enhanced AP-1-mediated transcription,
      required extracellular signal-regulated protein kinase ERK1/2 as a signal
      transducer and the activation of the transcription factors c-Jun and ternary
      complex factor. Together, these data suggest that the intracellular functions of
      TRPV1 stimulation may rely on the activation of a stimulus-regulated protein
      kinase and stimulus-responsive transcription factors.

PMID- 29452098
TI  - Features of COPD as Predictors of Lung Cancer.
AB  - BACKGROUND: Lung cancer is a leading cause of death and hospitalization for
      patients with COPD. A detailed understanding of which clinical features of COPD
      increase risk is needed. METHODS: We performed a nested case-control study of
      Genetic Epidemiology of COPD (COPDGene) Study subjects with and without lung
      cancer, age 45 to 80 years, who smoked at least 10-pack years to identify
      clinical and imaging features of smokers, with and without COPD, that are
      associated with an increased risk of lung cancer. The baseline evaluation
      included spirometry, high-resolution chest CT scanning, and respiratory
      questionnaires. New lung cancer diagnoses were identified over 8 years of
      longitudinal follow-up. Cases of lung cancer were matched 1:4 with control
      subjects for age, race, sex, and smoking history. Multiple logistic regression
      analyses were used to determine features predictive of lung cancer. RESULTS:
      Features associated with a future risk of lung cancer included decreased FEV1/FVC
      (OR, 1.28 per 10% decrease [95% CI, 1.12-1.46]), visual severity of emphysema
      (OR, 2.31, none-trace vs mild-advanced [95% CI, 1.41-3.86]), and respiratory
      exacerbations prior to study entry (OR, 1.39 per increased events [0, 1, and >=
      2] [95% CI, 1.04-1.85]). Respiratory exacerbations were also associated with
      small-cell lung cancer histology (OR, 3.57 [95% CI, 1.47-10]). CONCLUSIONS: The
      degree of COPD severity, including airflow obstruction, visual emphysema, and
      respiratory exacerbations, was independently predictive of lung cancer. These
      risk factors should be further studied as inclusion and exclusion criteria for
      the survival benefit of lung cancer screening. Studies are needed to determine if
      reduction in respiratory exacerbations among smokers can reduce the risk of lung
      cancer.

PMID- 29452099
TI  - A Systematic Review and Meta-Analysis Comparing Pigtail Catheter and Chest Tube
      as the Initial Treatment for Pneumothorax.
AB  - BACKGROUND: The optimal initial treatment approach for pneumothorax remains
      controversial. This systemic review and meta-analysis investigated the
      effectiveness of small-bore pigtail catheter (PC) drainage compared with that of
      large-bore chest tube (LBCT) drainage as the initial treatment approach for all
      subtypes of pneumothorax. METHODS: PubMed and Embase were systematically searched
      for observational studies and randomized controlled trials published up to
      October 9, 2017, that compared PC and LBCT as the initial treatment for
      pneumothorax. The investigative outcomes included success rates, recurrence
      rates, complication rates, drainage duration, and hospital stay. RESULTS: Of the
      11 included studies (875 patients), the success rate was similar in the PC
      (79.84%) and LBCT (82.87%) groups, with a risk ratio of 0.99 (95% CI, 0.93 to
      1.05; I2 = 0%). Specifically, PC drainage was associated with a significantly
      lower complication rate following spontaneous pneumothorax than LBCT drainage
      (Peto odds ratio: 0.49 [95% CI, 0.28 to 0.85]; I2 = 29%). In the spontaneous
      subgroup, PC drainage was associated with a significantly shorter drainage
      duration (mean difference, -1.51 [95% CI, -2.93 to -0.09]) and hospital stay
      (mean difference: -2.54 [95% CI, -3.16 to -1.92]; P < .001) than the LBCT group.
      CONCLUSIONS: Collectively, results of the meta-analysis suggest PC drainage may
      be considered as the initial treatment option for patients with primary or
      secondary spontaneous pneumothorax. Ideally, randomized controlled trials are
      needed to compare PC vs LBCT among different subgroups of patients with
      pneumothorax, which may ultimately improve clinical care and management for these
      patients. TRIAL REGISTRY: PROSPERO; No.: CRD42017078481; URL:
      https://www.crd.york.ac.uk/prospero/.

PMID- 29452100
TI  - A New, Noninvasive Method of Measuring Impaired Pulmonary Gas Exchange in Lung
      Disease: An Outpatient Study.
AB  - BACKGROUND: It would be valuable to have a noninvasive method of measuring
      impaired pulmonary gas exchange in patients with lung disease and thus reduce the
      need for repeated arterial punctures. This study reports the results of using a
      new test in a group of outpatients attending a pulmonary clinic. METHODS:
      Inspired and expired partial pressure of oxygen (PO2) and Pco2 are continually
      measured by small, rapidly responding analyzers. The arterial PO2 is calculated
      from the oximeter blood oxygen saturation level and the oxygen dissociation
      curve. The PO2 difference between the end-tidal gas and the calculated arterial
      value is called the oxygen deficit. RESULTS: Studies on 17 patients with a
      variety of pulmonary diseases are reported. The mean +/- SE oxygen deficit was
      48.7 +/- 3.1 mm Hg. This finding can be contrasted with a mean oxygen deficit of
      4.0 +/- 0.88 mm Hg in a group of 31 normal subjects who were previously studied
      (P < .0001). The analysis emphasizes the value of measuring the composition of
      alveolar gas in determining ventilation-perfusion ratio inequality. This factor
      is largely ignored in the classic index of impaired pulmonary gas exchange using
      the ideal alveolar PO2 to calculate the alveolar-arterial oxygen gradient.
      CONCLUSIONS: The results previously reported in normal subjects and the present
      studies suggest that this new noninvasive test will be valuable in assessing
      abnormal gas exchange in the clinical setting.

PMID- 29452102
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- 29452101
TI  - Cytokine Signaling Protein 3 Deficiency in Myeloid Cells Promotes Retinal
      Degeneration and Angiogenesis through Arginase-1 Up-Regulation in Experimental
      Autoimmune Uveoretinitis.
AB  - The suppressor of cytokine signaling protein 3 (SOCS3) critically controls immune
      cell activation, although its role in macrophage polarization and function
      remains controversial. Using experimental autoimmune uveoretinitis (EAU) as a
      model, we show that inflammation-mediated retinal degeneration is exaggerated and
      retinal angiogenesis is accelerated in mice with SOCS3 deficiency in myeloid
      cells (LysMCre/+SOCS3fl/fl). At the acute stage of EAU, the population of
      infiltrating neutrophils was increased and the population of macrophages
      decreased in LysMCre/+SOCS3fl/fl mice compared with that in wild-type (WT) mice.
      Real-time RT-PCR showed that the expression of tumor necrosis factor-alpha, IL
      1beta, interferon-gamma, granulocyte-macrophage colony-stimulating factor, and
      arginase-1 was significantly higher in the LysMCre/+SOCS3fl/fl EAU retina in
      contrast to the WT EAU retina. The percentage of arginase-1+ infiltrating cells
      was significantly higher in the LysMCre/+SOCS3fl/fl EAU retina than that in the
      WT EAU retina. In addition, bone marrow-derived macrophages and neutrophils from
      the LysMCre/+SOCS3fl/fl mice express significantly higher levels of chemokine (C
      C motif) ligand 2 and arginase-1 compared with those from WT mice. Inhibition of
      arginase using an l-arginine analog amino-2-borono-6-hexanoic suppressed
      inflammation-induced retinal angiogenesis without affecting the severity of
      inflammation. Our results suggest that SOCS3 critically controls the phenotype
      and function of macrophages and neutrophils under inflammatory conditions and
      loss of SOCS3 promotes the angiogenic phenotype of the cells through up
      regulation of arginase-1.

PMID- 29452103
TI  - Analysis of 13C labeling amino acids by capillary electrophoresis - High
      resolution mass spectrometry in developing flaxseed.
AB  - In context of fluxomic studies, 13C labeling analysis of amino acids are very
      important for solving the carbon flow calculation, because they are synthesized
      in various biosynthesis pathways and cellular compartments in plant cells.
      Traditionally, 13C labeling analysis are performed using low resolution mass
      spectrometry detector by GC-MS. We compared a method using capillary
      electrophoresis-high resolution mass spectrometry without derivatization and with
      better accuracy assessment of labeling measurements comparing to classical GC-MS.
      Our method allowed us to show that valine, leucine, alanine are not synthesized
      from the same pyruvate pool during the period of reserves accumulation in flax
      seeds.

PMID- 29452104
TI  - Improved protein determination assays obtained after substitution of copper
      sulfate by copper oxide nanoparticles.
AB  - Copper oxide nanoparticles (nano CuO) provide Cu2+ ions which can be easily
      harnessed for protein determination as an alternative to the use of copper
      sulfate (CuSO4). In the present work, nano CuO of size <25 nm were substituted
      for CuSO4 in two of the well-known protein assays viz. Lowry method and
      bicinchoninic acid (BCA) method. Use of nano CuO in the Lowry's assay had no
      effect on the assay time (30 min) but significantly lowered the limit of
      detection (LOD) from 0.01 to 0.001 MUg/ml, while the BCA method when performed
      using nano CuO resulted in notable reduction of not only the assay time from 30
      to 20 min but also the LOD from 0.1 to 0.001 MUg/ml. Nano CuO based protein
      determination in the human serum and urd bean seeds extract produced reliable,
      reproducible and consistent results. Nano CuO also alleviated the inhibition of
      both the methods by common interfering substances such as ammonium sulfate,
      glucose, EDTA, SDS, Triton X-100, dithiothreitol and 2-mercaptoethanol. Hence,
      successful modification and improvement of Lowry and BCA methods by substitution
      of CuSO4 with nano CuO for protein determination has been demonstrated.

PMID- 29452105
TI  - Label-free electrochemical aptasensor for detection of alpha-fetoprotein based on
      AFP-aptamer and thionin/reduced graphene oxide/gold nanoparticles.
AB  - Sensitive and accurate detection of tumor markers is critical to early diagnosis,
      point-of-care and portable medical supervision. Alpha fetoprotein (AFP) is an
      important clinical tumor marker for hepatocellular carcinoma (HCC), and the
      concentration of AFP in human serum is related to the stage of HCC. In this
      paper, a label-free electrochemical aptasensor for AFP detection was fabricated
      using AFP-aptamer as the recognition molecule and thionin/reduced graphene
      oxide/gold nanoparticles (TH/RGO/Au NPs) as the sensor platform. With high
      electrocatalytic property and large specific surface area, RGO and Au NPs were
      employed on the screen-printed carbon electrode to load TH molecules. The TH not
      only acted as a bridging molecule to effectively capture and immobilize AFP
      aptamer, but as the electron transfer mediator to provide the electrochemical
      signal. The AFP detection was based on the monitoring of the electrochemical
      current response change of TH by the differential pulse voltammetry. Under
      optimal conditions, the electrochemical responses were proportional to the AFP
      concentration in the range of 0.1-100.0 MUg/mL. The limit of detection was 0.050
      MUg/mL at a signal-to-noise ratio of 3. The proposed method may provide a
      promising application of aptamer with the properties of facile procedure, low
      cost, high selectivity in clinic.

PMID- 29452106
TI  - Nerve fibre layer degeneration and retinal ganglion cell loss long term after
      optic nerve crush or transection in adult mice.
AB  - We have investigated the long term effects of two different models of unilateral
      optic nerve (ON) lesion on retinal ganglion cells (RGCs) and their axons, in the
      injured and contralateral retinas of adult albino mice. Intact animals were used
      as controls. The left ON was intraorbitally crushed or transected at 0.5 mm from
      the optic disk and both retinas were analyzed at 2, 3, 5, 7, 14, 30, 45 or 90
      days after injury. RGCs were immunoidentified with anti-Brn3a, and their axons
      with anti-highly phosphorylated axonal neurofilament subunit H (pNFH). After both
      lesions, RGC death in the injured retinas is first significant at day 3, and
      progresses quickly up to 7 days slowing down till 90 days. In the same retinas,
      the anatomical loss of RGC axons is not evident until day 30. However, by two
      days after both lesions there are changes in the expression pattern of pNFH:
      axonal beads, axonal club- or bulb-like formations, and pNFH+RGC somas. The
      number of pNFH+RGC somata peak at day 5 after either lesion and is significantly
      higher than in intact retinas at all time points. pNFH+RGC somata are distributed
      across the retina, in accordance with the pattern of RGC death which is diffuse
      and homogenous. In the contralateral retinas there is no RGC loss, but there are
      few pNFH+RGCs from day 2 to day 90. In conclusion, in albino mice, axotomy
      induced RGC death precedes the loss of their intraretinal axons and occurs in two
      phases, a rapid and a slower, but steady, one. Injured retinas show similar
      changes in the pattern of pNFH expression and a comparable course of RGC loss.

PMID- 29452094
TI  - Evolving mechanisms of vascular smooth muscle contraction highlight key targets
      in vascular disease.
AB  - Vascular smooth muscle (VSM) plays an important role in the regulation of
      vascular function. Identifying the mechanisms of VSM contraction has been a major
      research goal in order to determine the causes of vascular dysfunction and
      exaggerated vasoconstriction in vascular disease. Major discoveries over several
      decades have helped to better understand the mechanisms of VSM contraction. Ca2+
      has been established as a major regulator of VSM contraction, and its sources,
      cytosolic levels, homeostatic mechanisms and subcellular distribution have been
      defined. Biochemical studies have also suggested that stimulation of Gq protein
      coupled membrane receptors activates phospholipase C and promotes the hydrolysis
      of membrane phospholipids into inositol 1,4,5-trisphosphate (IP3) and
      diacylglycerol (DAG). IP3 stimulates initial Ca2+ release from the sarcoplasmic
      reticulum, and is buttressed by Ca2+ influx through voltage-dependent, receptor
      operated, transient receptor potential and store-operated channels. In order to
      prevent large increases in cytosolic Ca2+ concentration ([Ca2+]c), Ca2+ removal
      mechanisms promote Ca2+ extrusion via the plasmalemmal Ca2+ pump and Na+/Ca2+
      exchanger, and Ca2+ uptake by the sarcoplasmic reticulum and mitochondria, and
      the coordinated activities of these Ca2+ handling mechanisms help to create
      subplasmalemmal Ca2+ domains. Threshold increases in [Ca2+]c form a Ca2+
      calmodulin complex, which activates myosin light chain (MLC) kinase, and causes
      MLC phosphorylation, actin-myosin interaction, and VSM contraction. Dissociations
      in the relationships between [Ca2+]c, MLC phosphorylation, and force have
      suggested additional Ca2+ sensitization mechanisms. DAG activates protein kinase
      C (PKC) isoforms, which directly or indirectly via mitogen-activated protein
      kinase phosphorylate the actin-binding proteins calponin and caldesmon and
      thereby enhance the myofilaments force sensitivity to Ca2+. PKC-mediated
      phosphorylation of PKC-potentiated phosphatase inhibitor protein-17 (CPI-17), and
      RhoA-mediated activation of Rho-kinase (ROCK) inhibit MLC phosphatase and in turn
      increase MLC phosphorylation and VSM contraction. Abnormalities in the Ca2+
      handling mechanisms and PKC and ROCK activity have been associated with vascular
      dysfunction in multiple vascular disorders. Modulators of [Ca2+]c, PKC and ROCK
      activity could be useful in mitigating the increased vasoconstriction associated
      with vascular disease.

PMID- 29452107
TI  - Trabecular meshwork morphogenesis: A comparative analysis of wildtype and
      anterior segment dysgenesis mouse models.
AB  - The trabecular meshwork (TM), a tissue residing in the iridocorneal angle of the
      eye, is the primary site of aqueous humor outflow and often develops abnormally
      in children with anterior segment dysgenesis (ASD). However, the cellular
      mechanisms underlying both normal and pathophysiological TM formation are poorly
      understood. Here, we improve the characterization of TM development via
      morphological and molecular analyses. We first assessed the TM of wild-type
      C57BL/6J mice at multiple time points throughout development (E15.5-P21). The
      morphology of TM cells, rate of cell division, presence of apoptotic cell death,
      and age of onset of an established TM marker (alphaSMA) were each assessed in the
      developing iridocorneal angle. We discovered that TM cells are identifiable
      histologically at P1, which coincided with both the onset of alphaSMA expression
      and a significant decrease in TM precursor cell proliferation. Significant
      apoptotic cell death was not detected during TM development. These findings were
      then used to assess two mouse models of ASD. Jag1 and Bmp4 heterozygous null mice
      display ASD phenotypes in the adult, including TM hypoplasia and corneal
      adherence to the iris. We further discovered that both mutants exhibited similar
      patterns of developmental TM dysgenesis at P1, P5, and P10. Our data indicate
      that P1 is an important time point in TM development and that TM dysgenesis in
      Jag1 and Bmp4 heterozygous null mice likely results from impaired TM cell
      migration and/or differentiation.

PMID- 29452109
TI  - Dengue infection in patients with febrile illness and its relationship to climate
      factors: A case study in the city of Jeddah, Saudi Arabia, for the period 2010
      2014.
AB  - Dengue is an important global arboviral disease with expanding geographical
      range. It is a major public health concern in Western Saudi Arabia since its
      first detection in the city of Jeddah in 1994. In this retrospective study, we
      examined dengue incidence among febrile patients suspected for acute dengue
      infection at King Abdulaziz University Hospital, Jeddah from 2010 to 2014 and we
      tried to determine the effect of climate factors on dengue incidence in the city.
      Acute dengue incidence rates among clinically suspected patients showed annual
      variation with a range from 29.3% to 57%. Male gender and 11-30 years age range
      were found to be risk factors for dengue infection in Jeddah. While dengue
      infections can be detected throughout the year, most cases occurred between March
      and July with peaks in May and June. Seasonality of dengue was found to be
      significantly associated with the decrease in relative humidity and increase in
      temperature within the range of ~25  degrees C to ~33  degrees C but not
      extremely hot temperatures. Moreover, we found that rainfall during winter
      (November to February) has a significant lag effect on dengue infection among
      febrile patients in the city. Jeddah is the second largest city in Saudi Arabia
      and a major hub for pilgrims because of its close proximity to the holy sites in
      the Kingdom. The observed high rates of acute dengue infections clearly show the
      endemicity of dengue in Jeddah. The observed higher incidence rates at young age
      are expected to cause an increase in severe dengue cases in the future especially
      that multiple dengue serotypes are co-circulating in the city. Furthermore, the
      significant association between the different climate factors and dengue and
      their impact on the disease seasonality should help in the effort to implement
      effective control and management measures to reduce dengue burden in the Kingdom.

PMID- 29452108
TI  - Effect of brimonidine, an alpha2 adrenergic agonist, on human meibomian gland
      epithelial cells.
AB  - We recently discovered that the anti-glaucoma pharmaceuticals timolol, a beta
      adrenergic antagonist, and pilocarpine, a cholinergic compound, negatively
      influence the morphology, proliferative capacity and survival of human meibomian
      gland epithelial cells (HMGECs). We hypothesize that another class of anti
      glaucoma drugs, the alpha2 adrenergic agonists, also acts directly on HMGECs to
      affect their structure and function. We tested this hypothesis. Immortalized (i)
      HMGECs were cultured with brimonidine, as well as clonidine (alpha2 agonist),
      phenylephrine (alpha1 agonist), RX821002 (inverse alpha2 agonist) and MK912
      (neutral alpha2 agonist) for up to 7 days. Cells were counted with a
      hemocytometer, and evaluated for morphology, signaling pathway activity, protein
      biomarker expression, and the accumulation of neutral lipids, phospholipids and
      lysosomes. Our findings demonstrate that brimondine treatment induces a dose
      dependent decrease in Akt signaling and proliferation of iHMGECs. In contrast,
      brimonidine also promotes a dose-dependent differentiation of iHMGECs, including
      an increase in neutral lipid, phospholipid and lysosome levels. These effects
      were paralleled by an inhibition of p38 signaling, and duplicated by cellular
      exposure to clonidine, but not phenylephrine. Brimonidine also enhanced the
      cellular content of sterol regulatory binding protein-1, a master regulator of
      lipid synthesis. Of particular interest, the putative alpha2 antagonists,
      RX821002 and MK912, did not interfere with brimonidine action, but rather
      stimulated IHMGEC differentiation. Our results support our hypothesis and
      demonstrate that alpha2 adrenergic agonists act directly on iHMGECs. However,
      these compounds do not elicit an overall negative effect. Rather, the alpha2
      agonists promote the differentiation of iHMGECs.

PMID- 29452110
TI  - Exploring the impact of house screening intervention on entomological indices and
      incidence of malaria in Arba Minch town, southwest Ethiopia: A randomized control
      trial.
AB  - House is the major site for malaria infection where most human-vector contact
      takes place. Hence, improving housing might reduce the risk of malaria infection
      by limiting house entry of vectors. This study aimed to explore the impact of
      screening doors and windows with wire meshes on density and entomological
      inoculation rate (EIR) of malaria vector, and malaria incidence, and assess the
      acceptability, durability, and cost of the intervention. The susceptibility
      status of malaria vector was also assessed. A two-arm randomized trial was done
      in Arba Minch Town, southwest Ethiopia. 92 houses were randomly included in the
      trial. The baseline entomological and malaria prevalence data were collected. The
      mosquito sampling was done twice per household per month by Centers for Diseases
      Control and Prevention (CDC) light traps for six months. The baseline prevalence
      of malaria was assessed by testing 396 (83% of the 447 study participants)
      household members in all the eligible houses. The 92 houses were then randomized
      into control and intervention groups using mosquito and malaria prevalence
      baseline data to make the two groups comparable except the intervention. Then, we
      put wire-mesh on doors and windows of 46 houses. Post-screening mosquito
      collection was done in each household twice per month for three months. Each
      household member was visited twice per month for six months to assess malaria
      episodes. The frequency of damage to different structure of screening was
      measured twice. In-depth interview was conducted with 24 purposely selected
      household heads from intervention group. Speciation of Anopheles mosquito was
      done by morphological key, and the circum-sporozoite proteins (CSPs) analysis was
      done using enzyme-linked immunosorbent assay. A generalized estimating equation
      with a negative binomial distribution was used to assess the impact of the
      intervention on the indoor density of vectors. Clinical malaria case data were
      analyzed using Poisson regression with generalized linear model. Screening doors
      and windows reduced the indoor density of An. arabiensis by 48% (mean ratio of
      intervention to control = 0.85/1.65; 0.52) (P = .001). Plasmodium falciparum CSP
      rate was 1.6% (3/190) in the intervention houses, while it was 2.7% (10/372) in
      the control houses. The protective efficacy of screening intervention from CSP
      positive An. arabiensis was 41% (mean ratio of intervention to control = 1.6/2.7;
      0.59), but was not statistically significant (P = .6). The EIR of An. arabiensis
      was 1.91 in the intervention group, whereas it was 6.45 in the control group. 477
      participants were followed for clinical malaria (50.1% from intervention and
      49.9% from the control group). Of 49 RDT positive cases, 45 were confirmed to be
      positive with microscopy. 80% (n = 36) cases were due to P. falciparum and the
      rest 20% (n = 9) were due to P. vivax. The incidence of P. falciparum in the
      intervention group was lower (IRR: 0.39, 95% CI: 0.2-0.80; P = .01) than in the
      control group. Using incidence of P. falciparum infection, the protective
      efficacy of intervention was 61% (95% CI: 18-83; P = .007). 97.9% of screened
      windows and 63.8% of screened doors were intact after eleven months of
      installation. Malaria mosquito was resistance (mortality rate of 75%) to the
      insecticide used for bed nets treatment. Almost all participants of intervention
      arm were willing to continue using screened doors and windows. Screening doors
      and windows reduced the indoor exposure to malaria vectors. The intervention is
      effective, durable and well-accepted. Hence, the existing interventions can be
      supplemented with house screening intervention for further reduction and
      ultimately elimination of malaria by reducing insecticide pressure on malaria
      vectors. However, further research could be considered in broad setting on
      different housing improvement and in the way how to scale-up for wider community.

PMID- 29452111
TI  - Recent progress in drug targets and inhibitors towards combating leishmaniasis.
AB  - Lesihmaniasis is one of the major neglected tropical disease caused by the
      parasite of the genus Leishmania. The disease has more than one clinical forms
      and the visceral form is considered fatal. With the lack of potential vaccine,
      chemotherapy is the major treatment source considered for the control of the
      disease in the infected people. Drugs including amphotericin B and miltefosine
      are widely used for the treatment, however, development of resistance by the
      parasite towards the administered drug and high-toxicity of the drug are of major
      concern. Hence, more attention has been shown on identifying new targets,
      effective inhibitors, and better drug delivery system against the disease. This
      review deals with recent studies on drug targets and exploring their essentiality
      for the survival of Leishmania. Further, new inhibitors for those targets, novel
      anti-leishmanial peptides and vaccines against leishmaniasis were discussed. We
      believe that this pool of information will ease the researchers to gain knowledge
      and help in choosing right targets and design of new inhibitors against
      Leishmaniasis.

PMID- 29452112
TI  - Molecular diagnosis of protozoan parasites by Recombinase Polymerase
      Amplification.
AB  - Infections caused by protozoan parasites affect millions of people around the
      world. Traditionally, diagnosis was made by microscopy, which is insensitive and
      in some cases not specific. Molecular methods are highly sensitive and specific,
      but equipment costs and personnel training limit its availability only to
      specialized centers, usually far from populations with the highest risk of
      infection. Inexpensive methods that can be applied at the point of care (POC),
      especially in places with limited health infrastructure, would be a major
      advantage. Isothermal amplification of nucleic acids does not require
      thermocyclers and is relatively inexpensive and easy to implement. Among
      isothermal methods, recombinase polymerase amplification (RPA) is sensitive and
      potentially applicable at POC. We and others have developed RPA diagnostic tests
      to detect protozoan parasites of medical importance. Overall, our results have
      shown high specificity with limits of detection similar to PCR. Currently, the
      optimization of RPA for use at the POC is under development, and in the near
      future the tests should become available to detect protozoan infections in the
      field. In this review we discuss the current status, challenges, and future of
      RPA in the field of molecular diagnosis of protozoan parasites.

PMID- 29452113
TI  - Technological innovation strategies for the specific treatment of Chagas disease
      based on Benznidazole.
AB  - Caused by Trypanosoma cruzi, Chagas disease is responsible for public health
      problems greater in magnitude than those attributed to malaria, schistosomiasis,
      or leishmaniasis. A factor in the socioeconomic development of poor countries,
      Chagas disease can cause death due to a high parasitic burden during its acute
      phase due and irreversible damage in organs such as the heart, esophagus, and
      colon during its chronic phase, even when the number of parasites is minimal. For
      treating Chagas disease, benznidazole (BNZ) remains the drug of choice and, in
      Latin America, the only drug on the market for treating the disease. However, BNZ
      has exhibited insufficient activity in the chronic phase of Chagas disease,
      required administration in large doses, prolonged treatment, and shown a high
      incidence of adverse reactions (vomiting, rash, peripheral neuropathy, and spinal
      cord depression), toxicity, and low solubility in water. As an antidote,
      pharmaceutical technologies have been introduced that can improve BNZ's
      solubility and dissolution, as well as reduce side effects in light of its
      bioavailability, all of which can enhance therapy for Chagas disease. In response
      to that trend, by conducting a literature review, we sought to identify current
      pharmaceutical technologies used in tandem with BNZ to improve therapy for Chagas
      disease. Documented techniques include emulsion and microemulsion formation,
      solutions, parenteral formulas, micronization, and drug delivery systems
      supported by the development of nanoparticles and cyclodextrins, solid
      dispersions, and the use of metal-organic frameworks as innovative excipients.
      Such technologies increase the water solubility of BNZ by 4-25-fold on
      dissolution and an 85% release with efficacy in only a few minutes, as recorded
      during a viability experiment with nanoparticle suspensions. That experiment
      demonstrated the need for a lower concentration of BNZ to kill 50% of
      trypomastigote forms of T. cruzi, described in terms of the formation of BNZ
      cyclodextrin complexes, and modulating and vectoring of the antichagasic by using
      metal-organic frameworks. Altogether, the promising results of research
      identified can enable strategies to improve solubility and efficacy of BNZ, as
      well as therapy for Chagas disease.

PMID- 29452114
TI  - The biodiversity of black flies (Diptera: Simuliidae) in Indonesia.
AB  - Indonesia is one of the megadiversity country in the world endowed with rich and
      unique biodiversity insects such as blackflies species (Diptera: Simuliidae).
      Blackflies are found almost anywhere with running water suitable as habitat for
      the immature stages. This family is one of the most important groups of blood
      sucking insects. This study collates the records of Simulium (Diptera:
      Simuliidae) in previous publications related fauna of Indonesia. Based on the
      results of this study, there were 124 species of blackflies in Indonesian
      Archipelago. All species are assigned to the genus Simulium Latreille s.l., and
      are placed into five subgenera, i.e. Gomphostilbia Enderlein, Morops Enderlein,
      Nevermannia Enderlein, Simulium Latreille s.str. and Wallacellum Takaoka. Further
      classification into 27 species groups within the subgenera were also made.
      Checklists of Indonesian Simuliidae are provided including data on the
      distribution of each species.

PMID- 29452115
TI  - Bioprosthetic Versus Mechanical Valve Replacement for Infective Endocarditis:
      Focus on Recurrence Rates.
AB  - BACKGROUND: Consensus guidelines for prosthesis selection in infective
      endocarditis recommend bioprosthetic or mechanical valve replacement based on
      life expectancy and comorbidity. However, contemporary outcome data are limited
      to institution series. METHODS: The outcomes of 3,447 patients identified from
      mandatory discharge databases in California and New York who had either primary
      isolated mitral (n = 1,603) or aortic (n = 1,844) valve replacement for active
      endocarditis between 1998 and 2010 were compared according to whether they
      received bioprosthetic (n = 1,673, 48.5%) or mechanical (n = 1,774, 51.5%)
      valves. Drug abusers were analyzed as a separate cohort. The primary outcome was
      endocarditis recurrence. Median follow-up time was 6.8 years (range, 0 to 12).
      Last follow-up for survival was December 31, 2015. RESULTS: Patients receiving
      bioprosthetic valves were older (60.4 +/- 14.9 versus 53.4 +/- 14.3 years, p <
      0.001), with more comorbidity. There was no significant difference in 12-year
      survival with bioprosthetic versus mechanical valves after mitral (adjusted
      hazard ratio 1.14, 95% confidence interval [CI]: 0.98 to 1.34, p = 0.10) or
      aortic (adjusted hazard ratio 1.10, 95% CI: 0.93 to 1.29, p = 0.26) valve
      replacement. Bioprosthetic and mechanical valves were associated with similar
      recurrence rates at 12 years: 10.4% (95% CI: 8.0% to 13.1%) versus 8.8% (95% CI:
      6.9% to 10.9%), adjusted Cox p = 0.79 after mitral replacement; and 9.4% (95% CI:
      7.5% to 11.6%) versus 10.0% (95% CI: 8.0% to 12.4%), adjusted Cox p = 0.81 after
      aortic valve replacement. CONCLUSIONS: Bioprosthetic and mechanical valves are
      associated with similar survival and freedom from endocarditis recurrence. These
      data support guideline recommendations that patient factors guide prosthesis
      choice in infective endocarditis.

PMID- 29452116
TI  - Invited Commentary.

PMID- 29452117
TI  - Hodgkin Lymphoma Presentation With Extensive Chest Wall Muscle Involvement in an
      Adult.

PMID- 29452118
TI  - Long-Term Outcome of Interrupted Arch Repair With Direct Anastomosis and
      Homograft Augmentation Patch.
AB  - BACKGROUND: This study analyzed outcomes of interrupted aortic arch (IAA) repair
      using a standardized technique to interpret the role of the arch repair on late
      outcomes in a complex and heterogeneous group of patients. METHODS: This single
      institution study covered the period from 1988 to 2015. A total of 120 cases of
      IAA were divided into four groups: IAA with ventricular septal defect (VSD) (n =
      38), IAA with a Norwood or Damus-Kaye-Stansel procedure (n = 41), IAA with
      truncus arteriosus (n = 24), and a miscellaneous group (n = 17). Arch repair was
      performed using a standard technique of direct anastomosis with homograft patch
      augmentation. RESULTS: IAAs were predominantly type B (n = 81, 68%), and type A
      (n = 34, 28%), with a significant association of type B with truncus arteriosus
      and of type A with an aortopulmonary window (p < 0.01). Survival was similar in
      all groups. The incidence of catheter or surgical reintervention was 18%
      (confidence interval [CI], 10% to 25%) at 5 years and 18% (CI, 10% to 25%) at 10
      years, with catheter reintervention more common and occurring before 18 months.
      Surgical reintervention occurred in 7% (CI, 2% to 13%) at 5 and 10 years and at
      10 years the reintervention rate was lower in the group with truncus arteriosus
      (0%) and in the group with a Norwood or Damus-Kaye-Stansel procedure (5%). There
      was no bronchial obstruction or aortic aneurysm. The Cox proportional hazard
      model showed that weight at surgery <2.5 kg and era of surgery were predictive of
      outcome, with surgical mortality rates in all variants dropping to 8.3% in the
      last 15 years of the study. CONCLUSIONS: Repair of IAA using direct anastomosis
      and patch augmentation is applicable to all variants and provides good long-term
      arch patency. Survival is strongly associated with weight at surgery.

PMID- 29452119
TI  - MicroRNAs-103/107 Regulate Autophagy in the Epidermis.
AB  - We have shown that microRNAs-103 and -107 (miRs-103/107) positively regulate end
      stage autophagy by ensuring dynamin activity in cultured keratinocytes. Most work
      in end-stage autophagy has been conducted using in vitro model systems. In vivo
      regulation of end-stage autophagy in epidermis remains unknown. Here, we used
      antagomirs to subcutaneously knock down miR-107 in the skin; conversely, we
      delivered miR-107 mimic subcutaneously via in vivo transfection to increase this
      miR. We found that antagomir-107 treatment in epidermis: (i) depleted endogenous
      miR-107; (ii) increased GFP-LC3 puncta in epidermal basal layers of GFP-LC3
      transgenic mice, indicative of an accumulation of autophagosomes; (iii) inhibited
      LC3 turnover and increased p62, suggesting an inhibition of autophagy flux; and
      (iv) increased phosphorylated dynamin (p-dynamin, an inactive form), a key enzyme
      in end-stage autophagy. Conversely, miR-107 mimic treatment in mouse epidermis:
      decreased GFP-LC3 puncta in basal layer, as well as p62 protein levels; and
      diminished p-dynamin, indicative of activation of this enzyme. In human epidermal
      keratinocytes, antagos-103/107 cause the formation of large vacuoles and an
      increase in p-dynamin, which can be rescued by inhibition of protein kinase C
      pathway. Collectively, these results suggest that the miR-103/107 family has a
      critical role in regulating end-stage autophagy in mouse epidermis via PLD1/2
      protein kinase C-dynamin pathway.

PMID- 29452120
TI  - Quantifying the Polygenic Contribution to Cutaneous Squamous Cell Carcinoma Risk.
AB  - Genetic factors play an important role in cutaneous squamous cell carcinoma risk.
      Genome-wide association studies have identified 21 single nucleotide
      polymorphisms associated with cutaneous squamous cell carcinoma risk. Yet no
      studies have attempted to quantify the contribution of heritability to cutaneous
      squamous cell carcinoma risk by calculating the population attributable risk
      using a combination of all discovered genetic variants. Using an additive multi
      locus linear logistic model, we determined the cumulative association of these 21
      genetic regions to cutaneous squamous cell carcinoma population attributable
      risk. We computed a multi-locus population attributable risk of 62%, suggesting
      that if the effects of all the risk alleles were removed from a population, the
      cutaneous squamous cell carcinoma risk would drop by 62%. Using stratified
      analysis, we also examined the impact of sex on polygenic risk score, and found
      that men have an increased relative risk throughout the spectrum of the polygenic
      risk score. Quantifying the impact of genetic predisposition on the proportion of
      cancer cases can guide future research decisions and public health policy
      planning.

PMID- 29452121
TI  - An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to
      Severe Patch-Type Alopecia Areata, Totalis, and Universalis.
AB  - Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of ~2%.
      In AA, the immune system targets the hair follicle, resulting in clinical hair
      loss. The prognosis of AA is unpredictable, and currently there is no definitive
      treatment. Our previous whole genome expression studies identified active immune
      circuits in AA lesions, including common gamma-chain cytokine and IFN pathways.
      Because these pathways are mediated through JAK kinases, we prioritized clinical
      exploration of small molecule JAK inhibitors. In preclinical trials in mice,
      tofacitinib successfully prevented AA development and reversed established
      disease. In our tofacitinib trial in 12 patients with moderate to severe AA, 11
      patients completed a full course of treatment with minimal adverse events.
      Following limited response to the initial dose (5 mg b.i.d.), the dose was
      escalated (10 mg b.i.d.) for nonresponding subjects. Eight of 12 patients
      demonstrated >=50% hair regrowth, while three patients demonstrated <50% hair
      regrowth, as measured by Severity in Alopecia Tool scoring. One patient
      demonstrated no regrowth. Gene expression profiles and Alopecia Areata Disease
      Activity Index scores correlated with clinical response. Our open-label studies
      of ruxolitinib and tofacitinib have shown dramatic clinical responses in moderate
      to severe AA, providing strong rationale for larger clinical trials using JAK
      inhibitors in AA. ClinicalTrials.gov ID NCT02299297.

PMID- 29452122
TI  - Peroxisome Proliferator-Activated Receptor-gamma-Mediated Signaling Regulates
      Mitochondrial Energy Metabolism in Human Hair Follicle Epithelium.

PMID- 29452123
TI  - We cannot see what she cannot ignore.

PMID- 29452124
TI  - Assessing the relationship between smoking and abdominal obesity in a National
      Survey of Adolescents in Brazil.
AB  - Abdominal obesity is even a stronger risk factor than overall obesity for
      noncommunicable chronic diseases. We examined the association between smoking and
      abdominal obesity among adolescents. Analyses were based on 38,813 subjects aged
      15-17 years from the Study of Cardiovascular Risks in Adolescents (ERICA), a
      Brazilian school-based national survey. Abdominal obesity was defined considering
      waist circumference (WC) percentiles. Statistical analyses, stratified by sex,
      considered the sample complex design. Poisson regression with robust variance was
      used to estimate smoker-to-nonsmoker abdominal obesity prevalence ratio (PR),
      adjusting by sociodemographic and lifestyle variables. Higher prevalence of
      abdominal obesity was observed among adolescents who consumed >1 cigarettes/day,
      comparing to nonsmokers: considering WC >80th percentile, adjusted-PR for boys
      was 1.27 [95%CI:1.05,1.52] and, for girls, 1.09 [95%CI:1.00,1.19]; using the 90th
      percentile, adjusted-PR were 2.24 [95%CI:1.70,2.94] and 1.27 [95%CI:1.12,1.46],
      respectively for male and female adolescents. Our findings suggest a positive
      association between cigarette consumption and the prevalence of abdominal
      obesity, for both boys and girls. Although other studies had found this
      association in adults, our study contributes to this discussion by assessing it
      in adolescents using a nationwide representative sample of medium and large
      municipalities.

PMID- 29452125
TI  - The creative brain in the figural domain: Distinct patterns of EEG alpha power
      during idea generation and idea elaboration.
AB  - This study investigated EEG activity in the upper alpha band during the well
      known Picture Completion Task of the Torrance Test of Creative Thinking (TTCT), a
      widely used creative ideation task in the figural domain. The application of a
      sophisticated computerized version of the TTCT facilitating the online assessment
      and digitalizing of participant's drawings allowed to separate two central stages
      of the creative ideation process (i.e., idea generation and idea elaboration).
      During idea generation, the participants' task was to generate an initial draft
      of an original and creative completion of the presented abstract lines and
      figures of the TTCT. During idea elaboration, the participants were required to
      mentally improve the originality of the initially generated idea/draft. Creative
      ideation in this figural task was generally associated with comparatively strong
      desynchronization of upper alpha power over parietal and occipital sites,
      indicating high visual/figural processing demands. Interestingly, the stage of
      idea elaboration was accompanied by a relative increase of upper alpha power at
      parietal and occipital sites compared to the stage of idea generation, indicating
      heightened top-down processing demands. Furthermore, task performance was
      associated with relative increases of upper alpha power at frontal sites and
      relative decreases at centro-temporal sites from the stage of idea generation to
      idea elaboration. This association suggests the importance of increased
      inhibitory control over stimulus-based bottom-up information and motor imagery in
      order to achieve more creative outputs. Taken together these findings add to the
      relevant literature in that they a) extend research on the relationship between
      EEG alpha activity and creativity to the figural domain, and b) support a
      multistage view of creative ideation, involving cognitive control and mental
      imagery as important components of creativity.

PMID- 29452126
TI  - FDA BRUDAC 2018 Criteria for Interstitial Cystitis/Bladder Pain Syndrome Clinical
      Trials: Future Direction for Research.

PMID- 29452127
TI  - Serotonergic psychedelics and personality: A systematic review of contemporary
      research.
AB  - Serotonergic psychedelics act as agonists at cortical 5-HT2A receptors and seem
      to induce personality changes. We conducted a systematic review of studies
      assessing the effects of these drugs on personality. Papers published from 1985
      2016 were included from PubMed, LILACS, and SciELO databases. Three hundred and
      sixty-nine studies were identified, and 18 were included. Specific personality
      traits, such as Absorption and Self-Transcendence, seem to influence the effects
      of psychedelics, and psychedelic drug users and nonusers appear to differ in some
      personality traits. Psychedelics administered in controlled settings may induce
      personality changes, such as increased Openness and Self-Transcendence. Increases
      in global brain entropy induced by acute psychedelic administration predicted
      changes in Openness, and Self-Transcendence was negatively correlated with
      cortical thinning of the posterior cingulate cortex in long-term religious
      ayahuasca users. Acute and long-term use of psychedelics is associated with
      personality changes that appear to be modulated by 5-HT2A receptors. These
      changes seem to induce therapeutic effects that should be further explored in
      randomized controlled studies.

PMID- 29452128
TI  - Are sleep disturbances causally linked to the presence and severity of psychotic
      like, dissociative and hypomanic experiences in non-clinical populations? A
      systematic review.
AB  - The present review aimed to 1) identify what sleep disturbances co-occur
      alongside psychotic-like, dissociative and hypomanic experiences; 2) assess the
      strength of potential associations between the severity of sleep disturbances and
      of the experiences studied; and 3) appraise evidence for a causal link. MedLine
      and PsycInfo were searched and 44 studies were deemed eligible. Results showed
      that insomnia was associated with all individual psychotic-like, dissociative and
      hypomanic experiences reviewed (effect size range: small-to-large). Parasomnias
      were associated with all psychotic-like experiences; however, there was evidence
      of variation in magnitude between individual experiences. An eveningness
      chronotype was associated with dissociative and hypomanic experiences, and
      circadian dysrhythmia was found alongside hypomania but not the other experiences
      reviewed. Finally, experimental sleep manipulation studies revealed a potential
      causal link between sleep loss and psychotic-like and dissociative experiences,
      although size and consistency of effects varied by specific experience. Future
      research, using experimental manipulations of sleep to address putative
      mechanisms, will enable questions of causality to be answered with more
      confidence.

PMID- 29452129
TI  - Multicenter initial experience with the EmboTrap device in acute anterior
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Mechanical thrombectomy predominantly using stent
      retrievers effectively restores cerebral blood flow and improves functional
      outcomes in patients with acute ischemic stroke. We sought to determine the
      safety and efficacy of mechanical thrombectomy using the EmboTrap device.
      MATERIALS AND METHODS: We identified 80 consecutive patients from 4 centers with
      acute ischemic stroke treated with EmboTrap from June 2015 to December 2016. All
      patients had confirmed large vessel occlusions in the anterior circulation using
      CT or MR angiography with salvageable tissue. We assessed baseline
      characteristics and treatment related parameters including onset-to-treatment
      time, recanalization success (mTICI 2b or greater), complications, and good
      clinical outcome (mRS 0 to 2). RESULTS: Successful recanalization was achieved in
      72 patients (90%). When considering the use of a second thrombectomy device as
      failure, the EmboTrap successfully recanalized 65 patients (81%), with complete
      (mTICI 3) recanalization in 40 patients (50%) within 1 or 2 passes. Median
      procedure time (groin to recanalization) was 35 minutes (8-161 minutes). During
      the procedure, distal emboli in previously unaffected territories were found in 5
      (6%) patients. There were 3 vasospasms (4%) and no vessel perforations.
      Intracranial hemorrhage on CT at day 1 was found in 18 17 (2321%) patients, none
      with subarachnoid hemorrhages, and 5 were symptomatic (6%). Good clinical outcome
      occurred in 4749/68 78 patients (6963%). CONCLUSIONS: In this multicenter
      retrospective study, the EmboTrap device achieved high recanalization rates, good
      clinical outcomes and was safe in treating acute stroke patients with large
      vessel occlusions.

PMID- 29452130
TI  - Magnetic combined cross-linked enzyme aggregates (Combi-CLEAs) for cofactor
      regeneration in the synthesis of chiral alcohol.
AB  - Magnetic Fe3O4 nanoparticles were prepared and embedded into the Combi-CLEAs to
      produce the magnetic Combi-CLEAs in this work. The process for magnetic Combi
      CLEAs preparation was optimized, and its properties were investigated. The
      optimum temperature, thermal stability and optimum pH of magnetic Combi-CLEAs
      were similar to those of Combi-CLEAs. The catalytic performance of magnetic Combi
      CLEAs was tested with the biosynthesis of (S)-ethyl 4-chloro-3-hydroxybutyrate
      ((S)-CHBE). Magnetic Combi-CLEAs could tolerate higher substrate concentration in
      the biphasic system. The catalytic efficiency and long-term operational stability
      of magnetic Combi-CLEAs were obviously superior to those of Combi-CLEAs in both
      aqueous and biphasic systems. Embedding of magnetic Fe3O4 nanoparticles endowing
      rigidity contributed to these improvements. Furthermore, the preparation of
      magnetic Combi-CLEAs was easy, and its recovery during multiple batches of
      reactions could be fulfilled by magnetic field. Aforementioned advantages make
      the magnetic Combi-CLEAs hold obvious potential for industrial application.

PMID- 29452131
TI  - Synergism between a cell penetrating peptide and a pH-sensitive cationic lipid in
      efficient gene delivery based on double-coated nanoparticles.
AB  - We report on the development of a highly efficient gene delivery system based on
      synergism between octaarginine (R8), a representative cell penetrating peptide,
      and YSK05, a recently developed pH-sensitive cationic lipid. Attaching a high
      density of R8 on the surface of YSK05 nanoparticles (NPs) that contained
      encapsulated plasmid DNA resulted in the formation of positively charged NPs with
      improved transfection efficiency. To avoid the development of a net positive
      charge, we controlled the density and topology of the R8 peptide through the use
      of a two-step coating methodology, in which the inner lipid coat was modified
      with a low density of R8 which was then covered with an outer neutral YSK05 lipid
      layer. Although used in low amounts, the R8 peptide improved cellular uptake and
      endosomal escape of the DNA encapsulated in YSK05 NPs, which resulted in a high
      transfection efficiency. The two-step coating design was essential for achieving
      a high degree of transfection, as evidenced by the low activity of NPs modified
      with the same amount of R8 in a regular single-coated design. In addition, a high
      transfection efficiency was not observed when R8 or YSK05 were used alone, which
      confirms the existence of a synergistic effect between both components. The
      results of this study indicate that cationic cell penetrating peptides have the
      ability to improve transfection activities without imparting a net positive
      charge when used in the proper amount and in conjunction with the appropriate
      design. This is expected to significantly increase the potential applications of
      these peptides as tools for augmenting the activity of lipid nanoparticles used
      in gene delivery.

PMID- 29452132
TI  - Effect of the GSTM1 gene deletion on glycemic variability, sympatho-vagal balance
      and arterial stiffness in patients with metabolic syndrome, but without diabetes.
AB  - AIMS: An increased rate of cerebrovascular complications in patients with
      metabolic syndrome (MetS) has been reported. Previous studies demonstrated an
      association between glycemic variability (GV) and cerebrovascular reactivity
      (CRV) in MetS, thus suggesting a putative role of GV on cerebrovascular events.
      Although the pathophysiological mechanism linking GV to damage is still to be
      elucidated, evidence suggests oxidative stress plays a crucial role. Since
      functional variants in glutathione S-transferases (GST) genes modulate the
      cellular detoxification processes, the aim of this study was to elucidate the
      involvement of GSTs in MetS and investigating the correlation with GV, arterial
      stiffness, and sympatho-vagal (SV) balance. METHODS: A hundred metabolic syndrome
      patients without diabetes underwent GST gene polymorphism analysis and a sub
      sample 36 patients were randomly selected to investigate the correlation between
      GST gene polymorphisms and GV, and sympatho-vagal (SV) balance and arterial
      stiffness. RESULTS: GSTM1 showed a significant association with several GV,
      arterial stiffness, and SV balance indexes. In particular, the GSTM1 deletion
      positively correlates with lower values of these indexes when compared to the
      presence of the gene. CONCLUSIONS: Therefore, we suggested a global influence of
      GSTM1 deletion on the GV, arterial stiffness, and SV balance pathways in MetS
      patients, probably also interacting with AMP-activated protein kinase (AMPK)
      regulation. Our novel findings indicate GSTM1 could be a risk locus in MetS
      development and shed light novel scenarios on the role of glucose fluctuations in
      neurological impairments.

PMID- 29452133
TI  - Some properties of the conditioned reconstructed process with Bernoulli sampling.
AB  - In many areas of genetics it is of relevance to consider a population of
      individuals that is founded by a single individual in the past. One model for
      such a scenario is the conditioned reconstructed process with Bernoulli sampling
      that describes the evolution of a population of individuals that originates from
      a single individual. Several aspects of this reconstructed process are studied,
      in particular the Markov structure of the process. It is shown that at any given
      time in the past, the conditioned reconstructed process behaves as the original
      conditioned reconstructed process after a suitable time-dependent change of the
      sampling probability. Additionally, it is discussed how mutations accumulate in a
      sample of particles. It is shown that random sampling of particles at the present
      time has the effect of making the mutation rate look time-dependent. Conditions
      are given under which this sampling effect is negligible. A possible extension of
      the reconstructed process that allows for multiple founding particles is
      discussed.

PMID- 29452134
TI  - Effect of High Intensity Interval Training on Cardiac Function in Children with
      Obesity: A Randomised Controlled Trial.
AB  - BACKGROUND: High intensity interval training (HIIT) confers superior
      cardiovascular health benefits to moderate intensity continuous training (MICT)
      in adults and may be efficacious for improving diminished cardiac function in
      obese children. The aim of this study was to compare the effects of HIIT, MICT
      and nutrition advice interventions on resting left ventricular (LV) peak systolic
      tissue velocity (S') in obese children. METHODS: Ninety-nine obese children were
      randomised into one of three 12-week interventions, 1) HIIT [n = 33, 4 * 4 min
      bouts at 85-95% maximum heart rate (HRmax), 3 times/week] and nutrition advice,
      2) MICT [n = 32, 44 min at 60-70% HRmax, 3 times/week] and nutrition advice, and
      3) nutrition advice only (nutrition) [n = 34]. RESULTS: Twelve weeks of HIIT and
      MICT were equally efficacious, but superior to nutrition, for normalising resting
      LV S' in children with obesity (estimated mean difference 1.0 cm/s, 95%
      confidence interval 0.5 to 1.6 cm/s, P < 0.001; estimated mean difference 0.7
      cm/s, 95% confidence interval 0.2 to 1.3 cm/s, P = 0.010, respectively).
      CONCLUSIONS: Twelve weeks of HIIT and MICT were superior to nutrition advice only
      for improving resting LV systolic function in obese children.

PMID- 29452135
TI  - Evidence-Based Exercise Recommendations to Reduce Hepatic Fat Content in Youth- a
      Systematic Review and Meta-Analysis.
AB  - The main purposes of this study were to elucidate the effects of supervised
      exercise training (ET) interventions on hepatic fat content and on non-alcoholic
      fatty liver disease (NAFLD) prevalence in children and adolescents and to provide
      information about the optimal ET prescription (type, intensity, volume, and
      frequency) needed to reduce hepatic fat content in youths. Supervised-ET
      interventions performed in children and adolescents (6-19 years) that provided
      results of exercise effects on hepatic fat content or NAFLD prevalence were
      included. Supervised-exercise significantly reduced hepatic fat content compared
      to the control groups. Lifestyle interventions that included supervised-ET
      significantly reduced the prevalence of NAFLD. This systematic review and meta
      analysis shows that supervised-ET could be an effective strategy in the
      management and prevention of NAFLD in children and adolescents. Both aerobic and
      resistance ET, at vigorous or moderate-to-vigorous intensities, with a volume
      >=60 min/session and a frequency >=3 sessions/week, aiming to improve
      cardiorespiratory fitness and muscular strength, had benefits on hepatic fat
      content reduction in youth. These data concur with the international
      recommendations of physical activity for health promotion in youth and may be
      useful when designing ET programs to improve and prevent hepatic steatosis in the
      pediatric population.

PMID- 29452136
TI  - Neuroprotective effects of valproic acid on brain ischemia are related to its
      HDAC and GSK3 inhibitions.
AB  - Valproic acid (VA) is an antiepileptic that is also used for the treatment of
      bipolar disorders. The objective was to evaluate the neuroprotective effects of
      VA on a brain ischemia model. The groups of male Wistar rats were: SO (sham
      operated), ischemic and ischemic treated with VA (25, 50 and 100 mg/kg, p.o.).
      After anesthesia with ketamine and xilazine, the animals were subjected to
      clamping of carotid arteries (30 min) and reperfusion. Except for the carotid
      clamping, the SO group was submitted to the same procedure. On the 7th day, the
      animals were behaviorally evaluated, euthanized and had their brain dissected for
      neurochemical and immunohistochemical assays. The data were analyzed by ANOVA and
      Tukey as the post hoc test. The results showed that VA reversed partly or
      completely the behavioral (locomotor activity and memory deficits), neurochemical
      (striatal DA and DOPAC levels, brain nitrite and lipid peroxidation) and
      immunohistochemical alterations (iNOS, COX-2, HDAC and GSK3) observed in the
      untreated ischemic group. VA neuroprotective effects are probably related to its
      anti-inflammatory and antioxidant properties, as well as to HDAC and GSK3
      inhibitory effects. These findings stimulate translational studies focusing on VA
      as a neuroprotective drug to be potentially used in the clinic for several
      neurological conditions.

PMID- 29452138
TI  - Exposure to low level of lead during preweaning period increases metallothionein
      3 expression and dysregulates divalent cation levels in the brain of young rats.
AB  - Lead (Pb) is a neurotoxic heavy metal, but the mechanism of its neurotoxicity is
      not clearly understood. Expression of metallothioneins (MTs) is induced in
      response to heavy metal exposure as a protective mechanism against heavy metal
      toxicity. There are several isoforms of MTs (MT-1 to 4), of which MT-3 is the
      neuron specific isoform, which also has neurite growth inhibitory effects.
      Whereas, the induction of MT-1 and 2 in response to Pb has been reported, the
      effect of Pb on the expression of MT-3 in the brain has not been documented. This
      study aimed at investigating the effect of Pb exposure on the expression of MT-3
      in the cerebrum and hippocampus. Wistar rat pups were exposed to Pb via their
      dams' drinking water (0.2% lead acetate in deionized water) from postnatal day
      (PND) 0 to 21 and directly via drinking water until PND30. Expression of MT-3 was
      measured by Western blot and quantitative RT-PCR. MT-3 localization was done by
      immunohistochemistry. Divalent metal ions were analysed by atomic absorption
      spectrophotometry. Levels of Pb in blood and cerebrum were significantly
      increased, while that of copper (Cu), zinc (Zn) and manganese (Mn) were
      significantly decreased in the Pb-exposed rats at both PND21 and PND30. MT-3
      protein was significantly increased in the cerebrum (by 2.5-fold) and in
      hippocampus (1.4 to 3.2-fold) in both PND21 and PND30 Pb-exposed rats over
      controls. MT-3 gene expression also increased in the cerebrum (by 42%), and in
      the hippocampus (by 65% and 43% in the PND21 and PND30 rats, respectively), in
      the Pb-exposed rats over controls, but the increase was statistically significant
      (p < 0.05) only in the PND30 rats. Pb exposure significantly increased (p < 0.05)
      percentage of MT-3 immunoreactive cells in Cornu Ammonis and dentate gyrus
      regions in the PND21 rats, and in the Cornu Ammonis 1, dentate gyrus and cortex
      regions in the PND30 rats. Our data thus provide convincing evidence that
      exposure to low levels of Pb during preweaning period increases the expression of
      MT-3 in the brain of rats.

PMID- 29452137
TI  - Aryl hydrocarbon receptor (AhR) mediated short-term effects of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) on bile acid homeostasis in mice.
AB  - The effects of the most potent aryl hydrocarbon receptor (AhR) agonist 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) on bile acid (BA) homeostasis was examined in
      male and female wild-type and AhR-null mice shortly after 4-day exposure, rather
      than at a later time when secondary non-AhR dependent effects are more likely to
      occur. TCDD had similar effects on BA homeostasis in male and female mice. TCDD
      decreased the concentration of total-(Sigma) BAs in liver by approximately 50%
      (all major BA categories except for the non-6,12-OH BAs), without decreasing the
      expression of the rate limiting BA synthetic enzyme (Cyp7a1) or altering the
      major BA regulatory pathways (FXR) in liver and intestine. Even though the Sigma
      BAs in liver were markedly decreased, the Sigma-BAs excreted into bile were not
      altered. TCDD decreased the relative amount of 12-OH BAs (TCA, TDCA, CA, DCA) in
      bile and increased the biliary excretion of TCDCA and its metabolites (TalphaMCA,
      TUDCA); this was likely due to the decreased Cyp8b1 (12alpha-hydroxylase) in
      liver. The concentration of Sigma-BAs in serum was not altered by TCDD,
      indicating that serum BAs do not reflect BA status in liver. However, proportions
      of individual BAs in serum reflected the decreased expression of Cyp8b1. All
      these TCDD-induced changes in BA homeostasis were absent in AhR-null mice. In
      summary, through the AhR, TCDD markedly decreases BA concentrations in liver and
      reduces the 12alpha-hydroxylation of BAs without altering Cyp7a1 and FXR
      signaling. The TCDD-induced decrease in Sigma-BAs in liver did not result in a
      decrease in biliary excretion or serum concentrations of Sigma-BAs.

PMID- 29452139
TI  - Reply by the Authors.

PMID- 29452140
TI  - Re: Fuchs et al.: Is Delayed Phase Computed Tomography Imaging Necessary After
      Blunt Renal Trauma in Children? (Urology 2017;113:187-191).

PMID- 29452141
TI  - A rich source of potential bioactive compounds with anticancer activities by
      Catharanthus roseus cambium meristematic stem cell cultures.
AB  - ETHNOPHARMACOLOGICAL IMPORTANCE: Catharanthus roseus (L.) G. Don. is an important
      medicinal plant with rich sources of remarkable health benefits consisting more
      than 100 alkaloids and significant amounts of bioactive compounds, which have
      been widely used as a folk medicine for treatment of several pathologies. THE AIM
      OF THE STUDY: In the present study, we isolated and cultured innately
      undifferentiated cambium meristematic cells (CMCs), which were observed stable
      cell growth, enhancement of bioactive compounds from C.roseus. MATERIALS AND
      METHODS: We attempted to determine the effect of association between time-course
      growth rates, bioactive compounds and terpenoids indole alkaloid (TIA) contents
      as well as antioxidant and anticancer efficacies of C. roseus CMC suspension
      culture treated by UV-C. RESULTS: The bioactive compounds, vincristine contents,
      and antioxidant power were noticed significantly higher in 60 min exposure at 5
      cm distances and with the directly collected sample (T7). A similar trend has
      also been noticed from the anticancer activity. Demonstration of TIA accumulation
      was found higher at 5 min exposure, at 20 cm distances and 48 h of incubation
      (T21) and the result of TIA contents had the highest correlation effects of
      anticancer activities. CONCLUSION: In the current study, we demonstrated that UV
      C light could enhance the production of the essential compounds and bioactivities
      in the CMCs of C. roseus, and thus, C. roseus CMCs have the potential to serve as
      an industrial platform for the production of bioactive alkaloids and antioxidant,
      anticancer activity. Moreover, additional efforts should be made to irradiate CMC
      suspension cultures from C. roseus with UV-C to achieve better pharmacological
      profiles.

PMID- 29452142
TI  - In Vitro-In Vivo Evaluation of an Oral Ghost Drug Delivery Device for the
      Delivery of Salmon Calcitonin.
AB  - An orally administered site-specific Oral Ghost Drug Delivery (OGDD) device was
      developed and evaluated for the administration of salmon calcitonin. In vitro
      drug release studies have been undertaken using biorelevant media and aspirated
      gastrointestinal fluid from a large white pig in addition to characterization of
      a formulated trimethyl chitosan blend formulated and prepared into a loaded mini
      pellet system. In vivo drug release analysis in a large white pig model has
      further been undertaken on the OGDD device and a commercial intramuscular
      injection to ascertain the release properties of the OGDD device in an animal
      model in comparison with the currently used treatment option for the
      administration of salmon calcitonin. Results of this study have detailed the
      success of the prepared system during both in vitro and in vivo analyses with the
      OGDD providing a greater control of release of salmon calcitonin when compared to
      the commercial product.

PMID- 29452143
TI  - Unusual Self-Assembly of the Recombinant Chlamydia trachomatis Major Outer
      Membrane Protein-Based Fusion Antigen CTH522 Into Protein Nanoparticles.
AB  - Sexually transmitted Chlamydia trachomatis infects more than 100 million people
      annually, and untreated chlamydia infections can cause severe complications.
      Therefore, there is an urgent need for a chlamydia vaccine. The Ctrachomatis
      major outer membrane protein (MOMP) is highly immunogenic but is a challenging
      vaccine candidate by being an integral membrane protein, and the immunogenicity
      depends on a correctly folded structure. We investigated the biophysical
      properties of the recombinant MOMP-based fusion antigen CTH522, which is tested
      in early human clinical trials. It consists of a truncated and cysteine-free
      version of MOMP fused to 4 variable domains from serovars D-G. In the native
      state, CTH522 did not exist as a monomer but showed an unusual self-assembly into
      nanoparticles with a negative zeta potential. In contrast to the beta-barrel
      structure of MOMP, native CTH522 contained no well-defined secondary structural
      elements, and no thermal transitions were measurable. Chemical unfolding resulted
      in monomers that upon removal of the denaturant self-assembled into higher order
      structures, comparable to the structure of the native protein. The conformation
      of CTH522 in nanoparticles is thus not entirely random and contains structural
      elements stabilized via denaturant-disruptable hydrophobic interactions. In
      conclusion, CTH522 has an unusual quaternary structure of supramolecular self
      assemblies.

PMID- 29452144
TI  - Recent progress in immune-metabolism.

PMID- 29452145
TI  - RNA biology-featuring the special issue guest editors "cancer letters".

PMID- 29452146
TI  - The Hippo/YAP1 pathway interacts with FGFR1 signaling to maintain stemness in
      lung cancer.
AB  - The Hippo pathway plays a critical role in organ size control, tissue homeostasis
      and tumor genesis through its key transcription regulator Yes-associated protein1
      (YAP1), but the mechanism underlying its role in lung cancer is unclear. We
      hypothesized that YAP1 influences FGFR1 signaling to maintain cancer stem-like
      cell (CSC) properties in FGFR1-amplified lung cancer. In support of this, our
      data confirms that expression levels of YAP1 are positively associated with those
      of FGFR1 in clinical lung carcinoma samples as measured by real-time PCR, western
      blot, and immunohistochemistry (IHC) staining. Mechanistically, YAP1 up-regulates
      FGFR1 expression at the level of promoter through the TEAD binding site while
      bFGF/FGFR1 induces YAP1 expression via large tumor suppressors 1(LATS1). In
      addition, the absence of YAP1 abolishes self-renewal ability in lung cancer.
      Furthermore, an orthotropic mouse model highlights the function of YAP1 in the
      initiation and metastasis of lung cancer. Verteporfin, a YAP1 inhibitor,
      effectively inhibits both YAP1 and FGFR1 expression in lung cancer. Thus, we
      conclude that YAP1 is a potential therapeutic target for lung cancer. Combined
      targeting of YAP1 and FGFR1 may provide benefits to patients with FGFR1-amplified
      lung cancer.

PMID- 29452147
TI  - Combination of Kras activation and PTEN deletion contributes to murine
      hepatopancreatic ductal malignancy.
AB  - Kras mutations are among the most common genetic abnormalities in human
      neoplasms, including cholangiocarcinomas, pancreatic cancer and colon cancer.
      PTEN has previously been associated with cholangiocarcinoma development in murine
      models. Here, we have established novel mouse models of neoplasms by liver
      specific and biliary-pancreatic Kras activation and PTEN deletion. By liver
      specific disruption of PTEN and activation of Kras in mice caused rapid
      development of intrahepatic biliary epithelial proliferative lesions
      (Intrahepatic cholangiocarcinoma, ICC), which progress through dysplasia to
      invasive carcinoma. In contrast, Kras activation in combination with heterozygous
      PTEN deletion induced mixed carcinomas of liver (both ICC and hepatocellular
      carcinoma, HCC), whereas Kras activation alone did not induce biliary tract
      neoplasm. Use of Sox9-Cre-LoxP-based approach to coordinately delete PTEN and
      activate Kras in the adult mouse resulted in not only development of low-grade
      biliary lesions (ICC and extrahepatic bile duct carcinoma, ECC) but also
      pancreatic carcinomas. Our data provide a functional link between PTEN gene
      status, hepatobiliary cell fate, and HCC, biliary carcinoma, pancreatic cancer
      pathogenesis, and present novel genetically engineered mouse models of PTEN loss
      driven malignancy.

PMID- 29452148
TI  - Complete inhibition of fetal movement in the day 40 pregnant goat model by the
      piperidine alkaloid anabasine but not related alkaloids.
AB  - Four chemically similar alkaloids, anabasine, anabaseine, epibatidine and
      dimethylphenylpiperazinium (DMPP), are potent nicotinic acetylcholine receptor
      agonists of fetal muscle nicotinic acetylcholine receptors in human TE-671 cells.
      Based on results with these cells, we hypothesized that the alkaloids would
      completely inhibit ultrasound-monitored fetal movement in a goat model.
      Different, single doses of anabasine, anabaseine, epibatidine, DMPP, or saline
      control were administered I.V. to pregnant goats on day 40 of gestation and the
      number of fetal movements per 5 min sample was measured by ultrasound at times 0,
      0.5, 1, 2, 4 and 8 h. The differences among does in fetal movements were more
      consistent at dosing and following recovery for doses of anabasine above 0.125
      mg/kg compared to the other compounds and dosages. Anabasine actions were dose
      dependent with an IC50 value of ~0.1 mg/kg, and, at a dose of 0.8 mg/kg,
      completely inhibited fetal movement for 1.5 h after dosing. Anabaseine,
      epibatidine, and DMPP failed to completely inhibit fetal movement in day 40
      pregnant goats at doses predicted to be effective. These results suggest that
      while experiments with TE-671 cells provide valuable information and predictions
      of the actions of plant alkaloids on fetal movement, in vivo experiments are
      still required in order to determine the ability of an alkaloid to inhibit fetal
      movement in livestock species. Moreover, other pharmacological properties such as
      receptor differences between mammalian species and differences in the
      pharmacokinetic properties of the alkaloids also are likely to weaken teratologic
      predictions based solely on the in vitro data.

PMID- 29452149
TI  - Facial gender but not emotion distinguishes neural responses of 10- to 13-year
      old children with social anxiety disorder from healthy and clinical controls.
AB  - OBJECTIVE: The current study examined neural and behavioral responses to angry,
      happy and neutral faces in childhood social anxiety disorder (SAD). METHOD:
      Behavioral (reaction time and accuracy) and electrocortical measures (P100, N170,
      EPN, LPP) were assessed during a facial emotion identification task in children
      (age 10-13) with SAD (n = 32), clinical controls with mixed anxiety disorders (n
      = 30), and healthy controls (n = 33). RESULTS: Overall, there were no group
      differences in behavioral or neural responses to emotional faces. However,
      children with SAD showed an attenuated LPP to male relative to female faces,
      while the opposite pattern emerged in the other two groups. DISCUSSION: Stimulus
      gender, but not facial emotion drove group-specific effects, which became evident
      in later, more elaborate stages of attention processing. The present study
      provides preliminary indications of gender effects in childhood SAD which should
      be further investigated by future studies.

PMID- 29452150
TI  - Cerebral blood flow velocity and autoregulation in paediatric patients following
      a global hypoxic-ischaemic insult.
AB  - AIM: To describe the cerebral blood flow velocity pattern and investigate
      cerebral autoregulation using transcranial Doppler ultrasonography (TCD)
      following a global hypoxic-ischaemic (HI) event in children. METHODS: This was a
      prospective, observational study in a quaternary-level paediatric intensive care
      unit. Intubated children, newborn to 17 years admitted to the PICU following HI
      injury (asphyxia, drowning, cardiac arrest) were eligible for inclusion. TCD was
      performed daily until post-injury day 8, discharge, or death, whichever occurred
      earliest. RESULTS: Twenty-six patients were enrolled. Median age was 3 years
      (0.33, 11.75), initial pH 6.95, and initial lactate 5.4. Median post
      resuscitation Glasgow Coma Score was 3T. Across the entire cohort, cerebral blood
      flow velocity (CBFV) was near normal on day 1. Flow velocity increased to a
      maximum median value of 1.4 standard deviations above normal on day 3 and slowly
      downtrended back to baseline by the end of the study period. Median Paediatric
      Extended Version of the Glasgow Outcome Score was 4 at three months. No patient
      in the favourable outcome group had extreme CBFV on day one, and only one patient
      in the favourable group had extreme CBFV on PID 2. In contrast, 38% of patients
      in the unfavourable group had extreme CBFV on PID 1 (p=.039 compared to frequency
      in favourable group), and 55% had extreme CBFV on PID 2 (p = .023 compared to
      frequency in favourable group). No patient had consistently intact cerebral
      autoregulation throughout the study period. CONCLUSIONS: Following a HI event,
      patients with favourable neurologic outcomes had flow velocity near normal
      whereas unfavourable outcomes had more extreme flow velocity. Intermittently
      intact cerebral autoregulation was more frequently seen in those with favourable
      neurologic outcomes though return to the autoregulatory baseline appears delayed.

PMID- 29452151
TI  - Does reduced mastication influence cognitive and systemic health during aging?
AB  - There is a growing body of literature which suggests that oral health and
      mastication can influence cognitive and systemic health during aging. However, it
      is currently unclear whether oral health, masticatory efficiency, cognitive
      health and systemic health merely deteriorate independently with age, or whether
      mechanisms exist linking mastication to cognitive and systemic health directly.
      The aim of this paper is to review the extent to which reduced mastication
      influences cognitive and systemic health during aging because this knowledge may
      underpin future interventions that improve quality of life. Current evidence
      suggests that a deterioration in mastication and oral health during aging can
      have: 1) direct effects on systemic health through mechanisms such as the
      migration of the oral microbiota into the systemic environment, and 2) indirect
      effects on systemic health through changes nutrient intake. A loss of teeth and
      reduction in masticatory efficiency during aging can have: 1) direct effects on
      cognitive performance and potentially impact cognitive health through mechanisms
      such as enhanced adult hippocampal neurogenesis, and 2) indirect effects on
      cognitive health through changes in nutrient intake. It is concluded that oral
      health and masticatory efficiency are modifiable factors which influence the risk
      poor cognitive and systemic health during aging, although it is currently
      premature to propose chewing-based interventions to slow the rate of cognitive
      decline and improve cognitive health during aging. Future research should include
      large-scale longitudinal studies which control for the types of confounding
      factors which concurrently influence the association between mastication and
      cognitive and systemic health.

PMID- 29452152
TI  - Behavioral and endocrine consequences of placentophagia in male California mice
      (Peromyscus californicus).
AB  - Ingestion of placenta by mammalian mothers can lead to changes in pain
      sensitivity, hormone levels, and behavioral responses to newborns. In some
      biparental mammals, males, in addition to females, ingest placenta when their
      offspring are born. In the monogamous, biparental California mouse (Peromyscus
      californicus), males first become attracted to placenta when cohabitating with
      their pregnant mate, and virgin males administered placenta are less neophobic
      than males given oil vehicle. In this study, we investigated the effects of
      placentophagia on pain sensitivity, anxiety-like behavior, behavioral responses
      to pups, and circulating corticosterone levels of both breeding and nonbreeding
      male California mice. We orally administered either a conspecific placenta or oil
      vehicle to male mice from three reproductive conditions (first-time fathers,
      first-time expectant fathers, and virgin males) and tested their pain sensitivity
      1 h later, as well as their exploratory behavior and paternal responsiveness in
      an open field 4 h post-treatment. We measured plasma corticosterone immediately
      after the open-field test. We found that placenta-treated males, independent of
      reproductive condition, traveled significantly longer distances in the open field
      than males treated with oil, indicative of lower anxiety. Additionally, fathers
      had shorter latencies to approach and to care for pups (i.e., huddling and
      licking pups), and spent more time engaging in these behaviors, than did age
      matched expectant fathers and virgin males, independent of treatment. We found no
      effect on plasma corticosterone levels or pain sensitivity as a result of either
      treatment or reproductive condition. These findings indicate that placenta
      ingestion decreases anxiety-related behaviors in male California mice, but might
      not influence pain sensitivity, paternal responsiveness, or plasma corticosterone
      concentrations.

PMID- 29452154
TI  - Study of petrolatum structure: Explaining its variable rheological behavior.
AB  - The rheological properties of petrolatum are dependent on both temperature and
      thermal history. How this thermal dependency can be explained is unclear. In the
      past it has been suggested that the structure of petrolatum consists of a three
      dimensional crystalline network. This has been established using old microscopic
      techniques only. Therefore a study on the microstructure of petrolatum was
      conducted using rheometry, DSC, pulsed NMR, polarized light microscopy and
      synchrotron X-ray. The combination of these techniques show that petrolatum is
      composed of 21% solid material at room temperature. This consists of partly
      crystalline lamellar sheets which are packed in stacks. The occurrence of these
      lamellar sheets is temperature dependent and the number of lamellar stacks is
      dependent on thermal history. It was shown that rheological differences in
      petrolatum can be explained by the number of lamellar stacks present, where more
      lamellar stacks result in more rigid petrolatum.

PMID- 29452153
TI  - Functionalization of nanodiamond with vitamin E TPGS to facilitate oral
      absorption of curcumin.
AB  - The purpose of this work was to develop a d-alpha-tocopherol polyethylene glycol
      1000 succinate (TPGS) decorated nanodiamond (ND) system loading water-insoluble
      curcumin (ND/CUR/TPGS) to improve the colloidal dispersity and oral
      bioavailability of the preparation. CUR was physically loaded into ND clusters,
      then TPGS was coated to the ND/CUR complex forming amorphous nanostructure on the
      interparticle nanocage of the ND substrate. The formulation of the nanocomplexes
      was optimized using response surface methodology, and the optimal ND/CUR/TPGS
      showed small particle size (196.32 nm), high drug loading efficiency (81.59%) and
      core-shell structure. In vitro release study demonstrated that the nanocomplexes
      provided a sustained release behavior. The absorptive concentration of
      ND/CUR/TPGS was dramatically improved in total intestinal tract compared with CUR
      suspension, and the absorption was controlled by multiple transcytosis
      mechanisms. Furthermore, the pharmacokinetic studies demonstrated that
      ND/CUR/TPGS had significantly higher Cmax (4.50-fold), larger AUC0-t (10.67
      fold), and longer MRT0-t (3.07-fold) in contrast with that of CUR suspension.
      Therefore, ND/CUR/TPGS presented great potential for oral delivery of insoluble
      and poorly permeable drugs.

PMID- 29452155
TI  - Comparative developmental biology of the cardiac inflow tract.
AB  - The vertebrate heart receives the blood through the cardiac inflow tract. This
      area has experienced profound changes along the evolution of vertebrates; changes
      that have a reflection in the cardiac ontogeny. The development of the inflow
      tract involves dynamic changes due to the progressive addition of tissue derived
      from the secondary heart field. The inflow tract is the site where oxygenated
      blood coming from lungs is received separately from the systemic return, where
      the cardiac pacemaker is established and where the proepicardium develops.
      Differential cell migration towards the inflow tract breaks the symmetry of the
      primary heart tube and determines the direction of the cardiac looping. In air
      breathing vertebrates, an inflow tract reorganization is essential to keep
      separate blood flows from systemic and pulmonary returns. Finally, the sinus
      venosus endocardium has recently been recognized as playing a role in the
      constitution of the coronary vasculature. Due to this developmental complexity,
      congenital anomalies of the inflow tract can cause severe cardiac diseases. We
      aimed to review the recent literature on the cellular and molecular mechanisms
      that regulate the morphogenesis of the cardiac inflow tract, together with
      comparative and evolutionary details, thus providing a basis for a better
      understanding of these mechanisms.

PMID- 29452156
TI  - Establishment of a PRKAG2 cardiac syndrome disease model and mechanism study
      using human induced pluripotent stem cells.
AB  - PRKAG2 cardiac syndrome is a distinct form of human cardiomyopathy characterized
      by cardiac hypertrophy, ventricular pre-excitation and progressive cardiac
      conduction disorder. However, it remains unclear how mutations in the PRKAG2 gene
      give rise to such a complicated disease. To investigate the underlying molecular
      mechanisms, we generated disease-specific hiPSC-derived cardiomyocytes from two
      brothers both carrying a heterozygous missense mutation c.905G>A (R302Q) in the
      PRKAG2 gene and further corrected the R302Q mutation with CRISPR-Cas9 mediated
      genome editing. Disease-specific hiPSC-cardiomyocytes recapitulated many
      phenotypes of PRKAG2 cardiac syndrome including cellular enlargement,
      electrophysiological irregularities and glycogen storage. In addition, we found
      that the PRKAG2-R302Q mutation led to increased AMPK activities, resulting in
      extensive glycogen deposition and cardiomyocyte hypertrophy. Finally we confirmed
      that disrupted phenotypes of PRKAG2 cardiac syndrome caused by the specific
      PRKAG2-R302Q mutation can be alleviated by small molecules inhibiting AMPK
      activity and be rescued with CRISPR-Cas9 mediated genome correction. Our results
      showed that disease-specific hiPSC-CMs and genetically-corrected hiPSC
      cardiomyocytes would be a very useful platform for understanding the pathogenesis
      of, and testing autologous cell-based therapies for, PRKAG2 cardiac syndrome.

PMID- 29452157
TI  - Hypertrophic cardiomyopathy mutation R58Q in the myosin regulatory light chain
      perturbs thick filament-based regulation in cardiac muscle.
AB  - Hypertrophic cardiomyopathy (HCM) is frequently linked to mutations in the
      protein components of the myosin-containing thick filaments leading to
      contractile dysfunction and ultimately heart failure. However, the molecular
      structure-function relationships that underlie these pathological effects remain
      largely obscure. Here we chose an example mutation (R58Q) in the myosin
      regulatory light chain (RLC) that is associated with a severe HCM phenotype and
      combined the results from a wide range of in vitro and in situ structural and
      functional studies on isolated protein components, myofibrils and ventricular
      trabeculae to create an extensive map of structure-function relationships. The
      results can be understood in terms of a unifying hypothesis that illuminates both
      the effects of the mutation and physiological signaling pathways. R58Q promotes
      an OFF state of the thick filaments that reduces the number of myosin head
      domains that are available for actin interaction and ATP utilization. Moreover
      this mutation uncouples two aspects of length-dependent activation (LDA), the
      cellular basis of the Frank-Starling relation that couples cardiac output to
      venous return; R58Q reduces maximum calcium-activated force with no significant
      effect on myofilament calcium sensitivity. Finally, phosphorylation of R58Q-RLC
      to levels that may be relevant both physiologically and pathologically restores
      the regulatory state of the thick filament and the effect of sarcomere length on
      maximum calcium-activated force and thick filament structure, as well as
      increasing calcium sensitivity. We conclude that perturbation of thick filament
      based regulation may be a common mechanism in the etiology of missense mutation
      associated HCM, and that this signaling pathway offers a promising target for the
      development of novel therapeutics.

PMID- 29452158
TI  - Protein kinase C epsilon mediates the inhibition of angiotensin II on the slowly
      activating delayed-rectifier potassium current through channel phosphorylation.
AB  - The slowly activating delayed rectifier K+ current (IKs) is one of the main
      repolarizing currents in the human heart. Evidence has shown that angiotensin II
      (Ang II) regulates IKs through the protein kinase C (PKC) pathway, but the
      related results are controversial. This study was designed to identify PKC
      isoenzymes involved in the regulation of IKs by Ang II and the underlying
      molecular mechanism. The whole-cell patch-clamp technique was used to record IKs
      in isolated guinea pig ventricular cardiomyocytes and in human embryonic kidney
      (HEK) 293 cells co-transfected with human KCNQ1/KCNE1 genes and Ang II type 1
      receptor genes. Ang II inhibited IKs in a concentration-dependent manner in
      native cardiomyocytes. A broad PKC inhibitor Go6983 (not inhibiting PKCepsilon)
      and a selective cPKC inhibitor Go6976 did not affect the inhibitory action of Ang
      II. In contrast, the inhibition was significantly attenuated by PKCepsilon
      selective peptide inhibitor epsilonV1-2. However, direct activation of PKC by
      phorbol 12-myristate 13-acetate (PMA) increased the cloned human IKs in HEK293
      cells. Similarly, the cPKC peptide activator significantly enhanced the current.
      In contrast, the PKCepsilon peptide activator inhibited the current. Further
      evidence showed that PKCepsilon knockdown by siRNA antagonized the Ang II-induced
      inhibition on KCNQ1/KCNE1 current, whereas knockdown of cPKCs (PKCalpha and
      PKCbeta) attenuated the potentiation of the current by PMA. Moreover, deletion of
      four putative phosphorylation sites in the C-terminus of KCNQ1 abolished the
      action of PMA. Mutation of two putative phosphorylation sites in the N-terminus
      of KCNQ1 and one site in KCNE1 (S102) blocked the inhibition of Ang II. Our
      results demonstrate that PKCepsilon isoenzyme mediates the inhibitory action of
      Ang II on IKs and by phosphorylating distinct sites in KCNQ1/KCNE1, cPKC and
      PKCepsilon isoenzymes produce the contrary regulatory effects on the channel.
      These findings have provided new insight into the molecular mechanism underlying
      the modulation of the KCNQ1/KCNE1 channel.

PMID- 29452160
TI  - Orchiectomy and letrozole differentially regulate synaptic plasticity and spatial
      memory in a manner that is mediated by SRC-1 in the hippocampus of male mice.
AB  - Hippocampal synaptic plasticity is the basis of spatial memory and cognition and
      is strongly regulated by both testicular androgens (testosterone, T) and
      hippocampal estrogens (17beta-estradiol, E2) converted from T by aromatase, which
      is inhibited by letrozole (LET), but the contribution of each pathway to spatial
      memory and the associated mechanisms are unclear. In this study, we first used
      orchiectomy (ORX) and LET injection to investigate the effects of T and
      hippocampal E2 on spatial memory and hippocampal synaptic plasticity. Next, we
      examined the changes in steroid receptors and steroid receptor coactivator-1 (SRC
      1) under these treatments. Finally, we constructed an SRC-1 RNA interference
      lentivirus and an AROM overexpression lentivirus to explore the roles of SRC-1
      under T replacement and AROM overexpression. The results revealed spatial memory
      impairment only after LET. LET induced more actin depolymerization and greater
      losses of spines, synapses, and postsynaptic proteins compared with ORX.
      Moreover, although ERalpha and ERbeta were affected by LET and ORX at similar
      levels, AR, GPR30, and SRC-1 were dramatically decreased by LET compared with
      ORX. Finally, the T and AROM overexpression-induced changes in synaptic proteins
      and actin polymerization were blocked by SRC-1 inhibition. These results
      demonstrate that testicular androgens play a limited role, whereas local E2 is
      more important for cognition, which may explain why castrated men such as eunuchs
      usually do not have cognitive disorders. These results also suggest a pivotal
      role of SRC-1 in the action of steroids; thus, SRC-1 may serve as a novel
      therapeutic target for cognitive disorders.

PMID- 29452159
TI  - CYP27A1 acts on the pre-vitamin D3 photoproduct, lumisterol, producing
      biologically active hydroxy-metabolites.
AB  - Prolonged exposure of the skin to UV radiation causes previtamin D3, the initial
      photoproduct formed by opening of the B ring of 7-dehydrocholesterol, to undergo
      a second photochemical reaction where the B-ring is reformed giving lumisterol3
      (L3), a stereoisomer of 7-dehydrocholesterol. L3 was believed to be an inactive
      photoproduct of excessive UV radiation whose formation prevents excessive vitamin
      D production. Recently, we reported that L3 is present in serum and that CYP11A1
      can act on L3 producing monohydroxy- and dihydroxy-metabolites which inhibit skin
      cell proliferation similarly to 1alpha,25-dihydroxyvitamin D3. In this study we
      tested the ability of human CYP27A1 to hydroxylate L3. L3 was metabolized by
      purified CYP27A1 to 3 major products identified as 25-hydroxyL3, (25R)-27
      hydroxyL3 and (25S)-27-hydroxyL3, by NMR. These three products were also seen
      when mouse liver mitochondria containing CYP27A1 were incubated with L3. The
      requirement for CYP27A1 for their formation by mitochondria was confirmed by the
      inhibition of their synthesis by 5beta-cholestane-3alpha,7alpha,12alpha-triol, an
      intermediate in bile acid synthesis which serves as an efficient competitive
      substrate for CYP27A1. CYP27A1 displayed a high kcat for the metabolism of L3 (76
      mol product/min/mol CYP27A1) and a catalytic efficiency (kcat/Km) that was 260
      fold higher than that for vitamin D3. The CYP27A1-derived hydroxy-derivatives
      inhibited the proliferation of cultured human melanoma cells and colony formation
      with IC50 values in the nM range. Thus, L3 is metabolized efficiently by CYP27A1
      with hydroxylation at C25 or C27 producing metabolites potent in their ability to
      inhibit melanoma cell proliferation, supporting that L3 is a prohormone which can
      be activated by CYP-dependent hydroxylations.

PMID- 29452161
TI  - C33-A cells transfected with E6*I or E6*II the short forms of HPV-16 E6,
      displayed opposite effects on cisplatin-induced apoptosis.
AB  - The HPV-16 E6/E7 bicistronic immature transcript produces 4 mature RNAs: the
      unspliced HPV-16 E6/E7pre-mRNA product and 3 alternatively spliced mRNAs. The 3
      spliced mRNAs encode short forms of the E6 oncoprotein, namely E6*I, E6*II and
      E6^E7. In this study we showed that transfection of C-33A cells with
      monocistronic constructs of these cDNAs fused to GFP, produced different effects
      on apoptosis, after the treatment with cisplatin. Transfection of C-33A cells
      with the full-length E6-GFP oncoprotein resulted in a 50% decrease in cell death,
      while the transfection with the E6*I-GFP construct showed only a 25% of
      diminution of cell death, compared to the control cells. Transfection with the
      E6^E7-GFP or E7-GFP construct had no effect on the number of the apoptotic cells,
      compared with control cells. Conversely, transfection with the E6*II construct
      resulted in higher cell death than the control cells. Taken together, these
      results suggested that E6*I or E6*II, the short forms of HPV-16 E6, displayed
      opposite effects on cisplatin-induced apoptosis, when transfected in C-33A cells.

PMID- 29452162
TI  - Pseudorabies virus induces autophagy to enhance viral replication in mouse neuro
      2a cells in vitro.
AB  - Autophagy of cytoplasmic components plays an essential role in the pathogenic
      infection process. Furthermore, research suggests that autophagy is an extremely
      important component of the innate immune response. Our study aimed to reveal the
      effect of virus-induced autophagy on pseudorabies virus (PRV) replication. Our
      results confirmed that light chain 3 (LC3)-I was converted into LC3-II after PRV
      infection; this transition is considered an important indicator of autophagy.
      Transmission electron microscopy (TEM) revealed that PRV infection could notably
      increase the number of autophagosomes in mouse neuro-2a (N2a) cells. In addition,
      LC3-II accumulated in response to chloroquine (CQ) treatment, indicating that PRV
      infection induced a complete autophagic flux response. Furthermore, our analyses
      verified differences in the magnitude of autophagy induction by two different PRV
      isolates, LA and ZJ01. Subsequent analysis showed that the induction of autophagy
      by rapamycin facilitated PRV replication, while inhibition of autophagy by 3
      methyladenine (3-MA) reduced PRV replication. These results indicated that PRV
      induced autophagy via the classical Beclin-1-Atg7-Atg5 pathway to enhance viral
      replication in N2a cells in vitro.

PMID- 29452163
TI  - Screening of binding proteins that interact with Chinese sacbrood virus VP3
      capsid protein in Apis cerana larvae cDNA library by the yeast two-hybrid method.
AB  - Chinese sacbrood virus (CSBV) causes larval death and apiary collapse of Apis
      cerana. VP3 is a capsid protein of CSBV but its function is poorly understood. To
      determine the function of VP3 and screen for novel binding proteins that interact
      with VP3, we conducted yeast two-hybrid screening, glutathione S-transferase pull
      down, and co-immunoprecipitation assays. Galectin (GAL) is a protein involved in
      immune regulation and host-pathogen interactions. The yeast two-hybrid screen
      implicated GAL as a major VP3-binding candidate. The assays showed that the VP3
      interacted with GAL. Identification of these cellular targets and clarifying
      their contributions to the host-pathogen interaction may be useful for the
      development of novel therapeutic and prevention strategies against CSBV
      infection.

PMID- 29452164
TI  - Proposal for a new subtype of the zoonotic genotype 3 Hepatitis E virus: HEV-3l.
AB  - The near-complete genomic sequences of two hepatitis E virus (HEV) strains,
      detected from feces of infected pigs, were obtained. Phylogenetic analysis and p
      distance comparisons of the complete coding regions showed a close relationship
      to the French swine strain FR-SHEV3c-like detected in 2006 (p-distance value
      0.101), belonging to HEV-3 but not assigned to any known subtype. The three HEV
      sequences showed, relatively high nucleotide distances (p-distance >0.129)
      compared to the other defined HEV subtype references and unclassified strains.
      The HEV classification criteria and the high sequence similarity suggest that
      these strains can be assigned to a putative novel subtype of genotype 3, HEV-3l.

PMID- 29452165
TI  - The beneficial role of early exercise training following stroke and possible
      mechanisms.
AB  - Exercise training is a regular therapy for stroke patients in clinic. However,
      whether the early exercise is beneficial for stroke patients is still
      controversial. The review was performed in databases of OVID, PUBMED, and ISI Web
      of Science, from respective inception to December 2017. In this review, we
      summarize the effect of different exercise intensity, initiation time, and style
      on ischemic stroke. Moreover, the possible mechanism is also discussed. The
      conclusion is that the voluntary exercise is better in promoting the functional
      recovery following stroke compared to forced exercise; too early initiated
      exercise might play a harmful role following stroke, while early initiated
      exercise might exert benefits after stroke; mild and moderate intensity exercise
      training could generate better neuroprotection in comparison with high intensity
      exercise training; early excise training could regulate the process of brain
      edema, cell apoptosis, oxidative damage, stem cells and other mechanisms in order
      to exert neuroprotection for brain.

PMID- 29452166
TI  - Metformin ameliorates the progression of atherosclerosis via suppressing
      macrophage infiltration and inflammatory responses in rabbits.
AB  - AIMS: The present study aimed to investigate the possible effects of metformin on
      the progression of atherosclerosis in a rabbit model. MAIN METHODS: Rabbits were
      randomly divided into three groups (n = 10): the control (Ctrl) group (fed with a
      chow diet), and two experimental groups, the AS group and the Met group (both
      received an atherogenic diet). After 2 weeks of acclimatization, the rabbits in
      the AS and Met groups were given a placebo and metformin, respectively, daily by
      gavage for 10 weeks. Plasma lipids and inflammatory cytokines were measured. The
      aorta was isolated for histological and immunohistochemical analysis. In vitro,
      human umbilical vein endothelial cells (HUVECs) were treated with metformin, and
      monocyte adhesion and adhesion molecule expression were measured. KEY FINDINGS:
      Metformin reduced plasma inflammatory cytokine levels but did not alter lipid
      content. Compared with that in the AS group, the atherosclerosis burden in the
      Met group was significantly decreased. The lesional macrophage content was
      reduced, but the lesional collagen content was not affected in the metformin
      treated rabbits, compared with the corresponding levels in the non-treated
      controls. Furthermore, the aortic mRNA expression levels of adhesion molecules
      and inflammatory cytokines in the Met group were also significantly reduced
      compared with those in the AS group. Metformin treatment reduced monocyte
      adhesion to endothelial cells (ECs) and adhesion molecule expression, and
      inhibited rabbit monocyte differentiation into macrophages and the macrophage
      inflammatory response. SIGNIFICANCE: Our results suggest that metformin impeded
      the progression of atherosclerosis, possibly by suppressing macrophage
      infiltration and inflammatory responses.

PMID- 29452167
TI  - microRNA-136 inhibits proliferation and promotes apoptosis and radiosensitivity
      of cervical carcinoma through the NF-kappaB pathway by targeting E2F1.
AB  - AIMS: Several microRNAs (miRs) are expressed aberrantly and associated with
      progression, tumorigenesis, and prognosis of haematological and solid tumors. The
      study aimed to identify the effects involved with microRNA-136 (miR-136) on the
      concurrent enhancement of proliferation, apoptosis and radiosensitivity of
      cervical carcinoma through the NF-kappaB signaling pathway by targeting E2F1.
      MAIN METHODS: Totally 338 patients with cervical carcinoma were recruited in this
      study. The expressions of miR-136, E2F1, p65, CyclinD1, Atm, Chk2, Bcl-2,
      Survivin and Bax were detected using RT-qPCR and Western blot analysis. Cells
      with highest miR-136 expression were subsequently assigned into different groups.
      Cell survival and apoptosis rate were detected by colony formation assay and flow
      cytometry, respectively. KEY FINDINGS: Compared to the sensitivity group, E2F1,
      p65, Bcl-2 and Survivin exhibited increased levels, while expression of CyclinD1,
      Atm, Chk2, Bax and miR-136 was reduced in the confrontation group. Cell survival
      rate was declined at 6 and 8 Gy of X-ray irradiation compared with 0, 2 and 4 Gy.
      Compared with the blank and NC groups, expression of E2F1, p65, Bcl-2 and
      Survivin was increased, while that of CyclinD1, Atm, Chk2, Bax and miR-136 was
      all decreased. The cell survival rate was increased; while apoptosis rate was
      decreased in the miR-136 inhibitor group. The trends observed in the miR-136
      mimics and siRNA-E2F1 groups were contradictory to the miR-136 inhibitor group.
      SIGNIFICANCE: Based on our results, miR-136 inhibits proliferation, while acting
      to promote apoptosis and radiosensitivity in cervical carcinoma by targeting E2F1
      through the NF-kappaB signaling pathway, resulting in improved prognoses.

PMID- 29452168
TI  - Non invasive diagnosis of acute cellular rejection after liver transplantation -
      Current opinion.

PMID- 29452169
TI  - Expression patterns of Toll like receptor (TLR)-2, TLR-4 and myeloid
      differentiation primary response gene 88 (MYD88) in renal transplant patients
      developing allograft dysfunction; a cohort study.
AB  - This cohort intends to determine the sequential dynamic changes in Toll-like
      receptor (TLR)-4, TLR-2, and myeloid differentiation primary response gene 88
      (MYD88) mRNA expressions in PBMCs and biopsy samples from kidney allograft
      recipients in relation to graft function. This study enrolled 52 renal transplant
      patients, 27 with well functioning graft (WFG) and 25 graft dysfunction (GD).
      Peripheral blood samples pre- and post-transplantation (days 2, 90 and 180) were
      collected to analyze mRNA expression levels of TLR-2, TLR-4, and MYD88 genes in
      relation to allograft function during one-year follow up. The mean dynamic
      changes of post-transplant TLR-2, TLR-4, and MYD88 mRNA expressions were
      significantly higher in GD compared to WFG patients (P = .001). ROC curve
      analysis based on glomerular filtration rate (GFR) index showed the area under
      curve (AUC) values for the genes: TLR-2(0.89;P < .001), TLR-4(0.86;P < .001), and
      MYD88(0.75;P = .003) in the third month post-transplantation for GD diagnosis.
      The calculated AUCs for the expressions of genes in allograft biopsies were
      0.94(TLR-2), 0.95(TLR-4), and 0.98(MYD88) in the sixth month post-transplant
      based on pathology report (P < .001). Our results indicate that sequential
      monitoring of the expression patterns of TLR-2, TLR-4, and MYD88 in PBMCs and
      biopsy samples could be considered as predictive biomarkers for early and late
      kidney allograft function.

PMID- 29452171
TI  - Evolution of model specific relative growth rate: Its genesis and performance
      over Fisher's growth rates.
AB  - Growth curve models play an instrumental role to quantify the growth of
      biological processes and have immense practical applications across disciplines.
      In the modelling approach, the absolute growth rate and relative growth rate
      (RGR) are two most commonly used measures of growth rates. RGR is empirically
      estimated by Fisher (1921) assuming exponential growth between two consecutive
      time points and remains invariant under any choice of the underlying growth
      model. In this article, we propose a new measure of RGR, called modified RGR,
      which is sensitive to the choice of underlying growth law. The mathematical form
      of the growth equations are utilized to develop the formula for model dependent
      growth rates and can be easily computed for commonly used growth models. We
      compare the efficiency of Fisher's measure of RGR and modified RGR to infer the
      true growth profile. To achieve this, we develop a goodness of fit testing
      procedure using Gompertz model as a test bed. The relative efficiency of the two
      rate measures is compared by generating power curves of the goodness of fit
      testing procedure. The asymptotic distributions of the associated test statistics
      are elaborately studied under Gompertz set up. The simulation experiment shows
      that the proposed formula has better discriminatory power than the existing one
      in identifying the true profile. The claim is also verified using existing real
      data set on fish growth. An algorithm for the model selection mechanism is also
      proposed based on the modified RGR and is generalized for some commonly used
      other growth models. The proposed methodology may serve as a valuable tool in
      growth studies in different research areas.

PMID- 29452170
TI  - Expression and significance of Sirt1 in renal allografts at the early stage of
      chronic renal allograft dysfunction.
AB  - OBJECTIVE: To investigate the expression and significance of Sirt1 in renal
      allografts at the early stage of chronic renal allograft dysfunction (CRAD).
      METHODS: CRAD rat models were established using classical orthotopic F344-Lewis
      kidney transplantation. F344 and Lewis uninephrectomized rats were used as
      controls. Twelve weeks after the operation, the rats were sacrificed for renal
      function, histological, immunohistochemistry and molecular biological analyses.
      RESULTS: The 24-h urinary protein excretion and serum creatinine levels, urine
      microalbumin/creatinine ratios, and Banff score sums were significantly increased
      in the CRAD group compared with those in the F344 and Lewis control groups. The
      degree of mononuclear cell infiltration and interstitial fibrosis (IF) was higher
      in the CRAD group than in the control groups. Sirt1, TGF-beta1, MCP-1, ICAM-1
      expression was up-regulated in CRAD. Furthermore, Sirt1 expression was negatively
      correlated with the 24-h urinary protein excretion and serum creatinine levels,
      Banff score sums, mononuclear cell infiltration and IF severity, and TGF-beta1,
      MCP-1 and ICAM-1 expression levels. CONCLUSION: Sirt1 might be involved in the
      pathogenic process of IF and inflammation at the early stage of CRAD. Thus, Sirt1
      represents a novel therapeutic strategy and target for the early prevention and
      treatment of CRAD.

PMID- 29452172
TI  - Joint evolution of dispersal propensity and site selection in structured
      metapopulation models.
AB  - We propose a novel mathematical model for a metapopulation in which dispersal
      occurs on two levels: juvenile dispersal from the natal site is mandatory but it
      may take place either locally within the natal patch or globally between patches.
      Within each patch, individuals live in sites. Each site can be inhabited by at
      most one individual at a time and it may be of high or low quality. A disperser
      immigrates into a high-quality site whenever it obtains one, but it immigrates
      into a low-quality site only with a certain probability that depends on the time
      within the dispersal season. The vector of these low-quality-site-acceptance
      probabilities is the site-selection strategy of an individual. We derive a proxy
      for the invasion fitness in this model and study the joint evolution of long
      distance-dispersal propensity and site-selection strategy. We focus on the way
      different ecological changes affect the evolutionary dynamics and study the
      interplay between global patch-to-patch dispersal and local site-selection. We
      show that ecological changes affect site-selection mainly via the severeness of
      competition for sites, which often leads to effects that may appear
      counterintuitive. Moreover, the metapopulation structure may result in extremely
      complex site-selection strategies and even in evolutionary cycles. The propensity
      for long-distance dispersal is mainly determined by the metapopulation-level
      ecological factors. It is, however, also strongly affected by the winter-survival
      of the site-holders within patches, which results in surprising non-monotonous
      effects in the evolution of site-selection due to interplay with long-distance
      dispersal. Altogether, our results give new additional support to the recent
      general conclusion that evolution of site-selection is often dominated by the
      indirect factors that take place via density-dependence, which means that
      evolutionary responses can rarely be predicted by intuition.

PMID- 29452173
TI  - Energy intake functions and energy budgets of ectotherms and endotherms derived
      from their ontogenetic growth in body mass and timing of sexual maturation.
AB  - Ectothermic and endothermic vertebrates differ not only in their source of body
      temperature (environment vs. metabolism), but also in growth patterns, in timing
      of sexual maturation within life, and energy intake functions. Here, we present a
      mathematical model applicable to ectothermic and endothermic vertebrates. It is
      designed to test whether differences in the timing of sexual maturation within an
      animal's life (age at which sexual maturity is reached vs. longevity) together
      with its ontogenetic gain in body mass (growth curve) can predict the energy
      intake throughout the animal's life (food intake curve) and can explain
      differences in energy partitioning (between growth, reproduction, heat production
      and maintenance, with the latter subsuming any other additional task requiring
      energy) between ectothermic and endothermic vertebrates. With our model we
      calculated from the growth curves and ages at which species reached sexual
      maturity energy intake functions and energy partitioning for five ectothermic and
      seven endothermic vertebrate species. We show that our model produces energy
      intake patterns and distributions as observed in ectothermic and endothermic
      species. Our results comply consistently with some empirical studies that in
      endothermic species, like birds and mammals, energy is used for heat production
      instead of growth, and with a hypothesis on the evolution of endothermy in
      amniotes published by us before. Our model offers an explanation on known
      differences in absolute energy intake between ectothermic fish and reptiles and
      endothermic birds and mammals. From a mathematical perspective, the model comes
      in two equivalent formulations, a differential and an integral one. It is derived
      from a discrete level approach, and it is shown to be well-posed and to attain a
      unique solution for (almost) every parameter set. Numerically, the integral
      formulation of the model is considered as an inverse problem with unknown
      parameters that are estimated using a series of empirical data.

PMID- 29452174
TI  - Dynamics analysis of epidemic and information spreading in overlay networks.
AB  - We establish an SIS-UAU model to present the dynamics of epidemic and information
      spreading in overlay networks. The overlay network is represented by two layers:
      one where the dynamics of the epidemic evolves and another where the information
      spreads. We theoretically derive the explicit formulas for the basic reproduction
      number of awareness R0a by analyzing the self-consistent equation and the basic
      reproduction number of disease R0d by using the next generation matrix. The
      formula of R0d shows that the effect of awareness can reduce the basic
      reproduction number of disease. In particular, when awareness does not affect
      epidemic spreading, R0d is shown to match the existing theoretical results.
      Furthermore, we demonstrate that the disease-free equilibrium is globally
      asymptotically stable if R0d<1; and the endemic equilibrium is globally
      asymptotically stable if R0d>1. Finally, numerical simulations show that
      information plays a vital role in preventing and controlling disease and
      effectively reduces the final disease scale.

PMID- 29452175
TI  - Replacement treatment during extinction training with the atypical dopamine
      uptake inhibitor, JHW-007, reduces relapse to methamphetamine seeking.
AB  - There are currently no approved medications to effectively counteract the effects
      of methamphetamine (METH), reduce its abuse and prolong abstinence from it. Data
      accumulated in recent years have shown that a range of N-substituted benztropine
      (BZT) analogues possesses psychopharmacological features consistent with those of
      a potential replacement or "substitute" treatment for stimulant addiction. On the
      other hand, the evidence that antidepressant therapy may effectively prevent
      relapse to stimulant seeking is controversial. Here, we compared in rats the
      ability of the BZT analogue and high affinity dopamine (DA) reuptake inhibitor,
      JHW-007, and the antidepressant, trazodone, administered during extinction
      sessions after chronic METH self-administration, to alter METH-primed
      reinstatement of drug seeking. The data showed that trazodone produced
      paradoxical effects on lever pressing during extinction of METH self
      administration, decreasing active, but increasing inactive, lever pressing. JHW
      007 did not have any observable effects on extinction training. Importantly, JHW
      007 significantly attenuated METH-primed reinstatement, whereas trazodone
      enhanced it. These findings lend support to the candidacy of selective DA uptake
      blockers, such as JHW-007, as potential treatments for METH addiction, but not to
      the use of antidepressant medication as a single therapeutic approach for relapse
      prevention.

PMID- 29452176
TI  - Calcium channel blocker use reduces incident dementia risk in elderly
      hypertensive patients: A meta-analysis of prospective studies.
AB  - Calcium channel blockers (CCBs) are an established class of drug for the
      management of hypertension. Observational studies have found that CCB use is
      associated with a reduction in the risk of developing dementia; however, studies
      have variably linked the CCBs use with the risk of dementia. This meta-analysis
      aims to assess whether, in elderly hypertensive patients, the use of CCBs alters
      the risk of developing dementia. We searched PubMed, Embase and Cochrane from
      August 2013 to 21st August 2017. Studies were screened on the basis of title and
      abstract. Quality of the included studies was assessed using the Newcastle-Ottawa
      Scale (NOS). The primary outcome was an estimate of the risk of dementia in
      elderly hypertensive CCBs users. The pooled relative risk (RR) was calculated
      using a generic inverse variance method. A subgroup analysis was also performed
      based on CCB class. Statistical analyses were performed using Review Manager
      Version 5.3. The meta-analysis included ten studies comprising 75,239 patients
      (53.16% female) with a median age and follow-up duration of 72.24 years and 8.21
      years respectively. All of the studies were of high quality. The use of CCBs was
      associated with a significant reduction in the risk of developing dementia in
      elderly hypertensive patients (RR 0.70 [95% CI: 0.58-0.85] p = 0.0003) compared
      to those not using CCBs. In subgroup analysis we found that the dihydropyridine
      class was associated with a 44% [RR 0.56 (95% CI: 0.40-0.78) p = 0.0005]
      reduction in the dementia risk. The use of CCBs was associated with a significant
      reduction in the risk of developing dementia in elderly hypertensive patients.

PMID- 29452177
TI  - Development and validation of prediction models for the risks of diabetes-related
      hospitalization and in-hospital mortality in patients with type 2 diabetes.
AB  - OBJECTIVES: Diabetes is a major cause of hospitalization and in-hospital
      mortality. However, a scoring system that can be used to identify diabetic
      patients at risk of diabetes-related hospitalization and in-hospital mortality is
      lacking. METHODS: We included 32,653 patients in this retrospective cohort study.
      All recruited patients had type 2 diabetes, were 30-84 years of age, and were
      enrolled in the National Diabetes Care Management Program over the period of 2001
      2003. We used the Cox proportional hazard regression model to derive risk scores.
      The predictive accuracy of the models was evaluated using receiver operating
      characteristic curves. We conducted the Hosmer-Lemeshow test to assess the
      agreement between predicted and observed risks. RESULTS: Over a follow-up period
      of eight years, 6243 patients were hospitalized for diabetes-related events, and
      2048 deaths were registered in hospital records. For the one-, three-, five-, and
      eight-year periods, the areas under the curve (AUC) for diabetes-related
      hospitalization in the validation set were 0.80, 077, 0.76, and 0.74,
      respectively. The corresponding values for in-hospital mortality in the
      validation set were 0.87, 080, 0.77, and 0.76. The goodness-of-fit test showed
      that the predicted and observed probabilities in the one-, three-, five-, and
      eight-year periods were similar for diabetes-related hospitalization and in
      hospital mortality in the validation set (all p values > 0.05). CONCLUSION: We
      developed models for the estimation of the risks of diabetes-related
      hospitalization and in-hospital mortality in patients with type 2 diabetes. The
      models may be used to identify diabetic patients who are at high risk for
      hospital admission and in-hospital mortality.

PMID- 29452178
TI  - Effects of canagliflozin versus glimepiride on adipokines and inflammatory
      biomarkers in type 2 diabetes.
AB  - OBJECTIVE: Type 2 diabetes and obesity are pro-inflammatory states associated
      with increased risk of cardiovascular disease. Canagliflozin, an SGLT2 inhibitor,
      demonstrated superiority in lowering HbA1c versus glimepiride with less
      hypoglycemia and greater weight reduction via loss of fat mass in a 52-week trial
      of type 2 diabetes patients. This post hoc, exploratory analysis assessed the
      effects of canagliflozin versus glimepiride on select adipokines, inflammatory
      biomarkers, and chemokines. METHODS: Changes from baseline to Week 52 in serum
      leptin, adiponectin, IL-6, TNFalpha, CRP, PAI-1, VCAM-1, and MCP-1 were measured
      in a randomly selected subset of type 2 diabetes patients on metformin receiving
      canagliflozin 300 mg (n = 100) or glimepiride (n = 100) in the overall study.
      Correlations between change in biomarkers and change in select metabolic and
      anthropometric variables were assessed. RESULTS: At Week 52, canagliflozin
      decreased median serum leptin by 25% (95% CI: -34%, -15%) and increased median
      serum adiponectin by 17% (95% CI: 11%, 23%) compared with glimepiride. There was
      a 22% reduction in median serum IL-6 (95% CI: -34%, -10%) and a 7% increase in
      median serum TNFalpha (95% CI: 1%, 12%) with canagliflozin versus glimepiride. No
      between-group differences were observed with the other biomarkers. The decrease
      in serum leptin with canagliflozin was correlated with change in weight (r >=
      0.3) only; the increase in adiponectin and decrease in IL-6 with canagliflozin
      occurred independently of changes in HbA1c, weight, or lipids. CONCLUSIONS: These
      results indicate that canagliflozin may improve adipose tissue function and
      induce changes in serum leptin, adiponectin, and IL-6 that favorably impact
      insulin sensitivity and cardiovascular disease risk.

PMID- 29452179
TI  - Massively parallel C. elegans tracking provides multi-dimensional fingerprints
      for phenotypic discovery.
AB  - BACKGROUND: The nematode worm C. elegans is a model organism widely used for
      studies of genetics and of human disease. The health and fitness of the worms can
      be quantified in different ways, such as by measuring their bending frequency,
      speed or lifespan. Manual assays, however, are time consuming and limited in
      their scope providing a strong motivation for automation. NEW METHOD: We describe
      the development and application of an advanced machine vision system for
      characterising the behaviour of C. elegans, the Wide Field-of-View Nematode
      Tracking Platform (WF-NTP), which enables massively parallel data acquisition and
      automated multi-parameter behavioural profiling of thousands of worms
      simultaneously. RESULTS: We screened more than a million worms from several
      established models of neurodegenerative disorders and characterised the effects
      of potential therapeutic molecules for Alzheimer's and Parkinson's diseases. By
      using very large numbers of animals we show that the sensitivity and
      reproducibility of behavioural assays is very greatly increased. The results
      reveal the ability of this platform to detect even subtle phenotypes. COMPARISON
      WITH EXISTING METHODS: The WF-NTP method has substantially greater capacity
      compared to current automated platforms that typically either focus on
      characterising single worms at high resolution or tracking the properties of
      populations of less than 50 animals. CONCLUSIONS: The WF-NTP extends
      significantly the power of existing automated platforms by combining enhanced
      optical imaging techniques with an advanced software platform. We anticipate that
      this approach will further extend the scope and utility of C. elegans as a model
      organism.

PMID- 29452180
TI  - The M-Maze task: An automated method for studying fear memory in rats exposed to
      protracted aversive conditioning.
AB  - BACKGROUND: Fear conditioning (FC) in rodents is the most used animal model to
      investigate the neurobiology of posttraumatic stress disorder (PTSD). Although
      research using FC has generated a better understanding of fear memories, studies
      often rely on mild or moderate FC training and behavioral analysis generally
      focuses on measuring freezing responses within few test sessions. NEW METHOD: We
      introduce the M-Maze task, a system that measures extinction of conditioned fear
      using suppression of operant behavior. The apparatus consists of an M-shaped maze
      where rats are trained to alternate nose poking at two pellet dispensers.
      Proximity sensors measure the animal's locomotion, as well as the latencies and
      number of operant behaviors. Here we also describe the protracted aversive
      conditioning (PAC), a rat model of severe fear that induces resistant extinction
      following a 4-day conditioning protocol that combines delay, unpredictable, and
      short- and long-trace conditioning. RESULTS: An intense one-day auditory FC
      protocol induced a sharp elevation in transit time and suppression of nose pokes
      by conditioned cues, but in contrast to what is found in PTSD patients, fear
      extinction was rapidly observed. On the other hand, PAC alone or in combination
      with exposure to single prolonged stress induced persistent extinction
      impairments in M-Maze tests, as well as enhanced anxiety, and social withdrawal.
      COMPARISON WITH OTHER EXISTING METHODS: The M-Maze task is fully automated and
      allows multiple animals to be tested simultaneously in long-term experiments.
      Moreover, PAC training can be an alternative approach to study extinction
      resistant fear. CONCLUSIONS: The M-Maze task allows rapid and unbiased
      measurements of fear-induced suppression. We suggest that long-term assessment of
      extinction impairments would lead to a better understanding of the neurobiology
      of persistent fear and the screening for new therapies.

PMID- 29452181
TI  - The demosponge Pseudoceratina purpurea as a new source of fibrous chitin.
AB  - Among marine demosponges (Porifera: Demospongiae), only representatives of the
      order Verongiida have been recognized to synthetize both biologically active
      substances as well as scaffolds-like fibrous skeletons made of structural
      aminopolysaccharide chitin. The unique 3D architecture of such scaffolds open
      perspectives for their applications in waste treatment, biomimetics and tissue
      engineering. Here, we focus special attention to the demosponge Pseudoceratina
      purpurea collected in the coastal waters of Singapore. For the first time the
      detailed description of the isolation of chitin from the skeleton of this sponge
      and its identification using diverse bioanalytical tools were carried out.
      Calcofluor white staining, FTIR analysis, electrospray ionization mass
      spectrometry (ESI-MS), SEM, and fluorescence microscopy as well as a chitinase
      digestion assay were applied in order to confirm with strong evidence the finding
      of alpha-chitin in the skeleton of P. purpurea. We suggest that the discovery of
      chitin within representatives of Pseudoceratinidae family is a perspective step
      in evaluation of these verongiid sponges as novel renewable sources for both
      chitin and biologically active metabolites, which are of prospective use for
      marine oriented biomedicine and pharmacology, respectively.

PMID- 29452182
TI  - Mussel-inspired fabrication of konjac glucomannan/microcrystalline cellulose
      intelligent hydrogel with pH-responsive sustained release behavior.
AB  - Intelligent hydrogels are attractive biomaterials for various applications,
      however, fabricating a hydrogel with both adequate self-healing ability and
      mechanical properties remains a challenge. Herein, a series of novel intelligent
      konjac glucomannan (KGM)/microcrystalline cellulose (MCC) hydrogels were prepared
      vis the mussel-inspired chemistry. MCC was firstly functionalized by the
      oxidative polymerization of dopamine, and the intelligent hydrogels were obtained
      by mixing aqueous solutions of KGM and functionalized MCC (PDMCC). By introducing
      PDMCC, a more compact interconnected porous structure formed for the resulting
      hydrogels. The self-healing ability and mechanical properties of intelligent
      hydrogels were dependence on the PDMCC content. Compared with KGM hydrogels,
      KGM/PDMCC hydrogels exhibited a more distinct pH sensitivity and a lower initial
      burst release, which was attributed to the compact structure and strong
      intermolecular hydrogen bond interaction between PDMCC and KGM. These results
      suggest that the KGM/PDMCC intelligent hydrogels may be promising carriers for
      controlled drug delivery.

PMID- 29452183
TI  - Purification, structural elucidation, and anti-inflammatory activity of xylosyl
      galactofucan from Armillaria mellea.
AB  - A xylosyl 1,3-galactofucan (AMPS-III) was isolated and identified as a novel anti
      inflammatory agent from an edible fungus, Armillaria mellea. The characteristics
      chemical structure of AMPS-III including the linkages of compositional
      monosaccharides and structure of the repeat unit were depicted and elucidated by
      proton, carbon and two-dimensional nuclear magnetic resonance techniques. AMPS
      III was chemically proposed to have a partial 4-O-xylosylated 1,3-linked alpha-d
      galactosyl-interlaced alpha-l-fucan composed of a pentadecasaccharide repeat unit
      with a molecular mass approximately 13 kDa. AMPS-III significantly suppressed the
      release of tumor necrosis factor-alpha (TNF-alpha) and cytokine monocyte
      chemotactic protein-1 (MCP-1) in RAW264.7 macrophages and EAhy926 following LPS
      and TNF-alpha induction. The results provide helpful evidences for application of
      AMPS-III as anti-inflammatory food supplements.

PMID- 29452184
TI  - Production of chitinase from Escherichia fergusonii, chitosanase from
      Chryseobacterium indologenes, Comamonas koreensis and its application in N
      acetylglucosamine production.
AB  - The important platform polysaccharide N-acetylglucosamine (GlcNAc) has great
      potential to be used in the fields of food, cosmetics, agricultural,
      pharmaceutical, medicine and biotechnology. This GlcNAc is being produced by
      traditional methods of environment-unfriendly chemical digestion with strong
      acids. Therefore, researchers have been paying more attention to enzymatic
      hydrolysis process for the production of GlcNAc. Hence, in this study, we
      isolated novel chitinase (Escherichia fergusonii) and chitosanase
      (Chryseobacterium indologenes, Comamonas koreensis) producing strains from Korean
      native calves feces, and developed the potential of an eco-friendly microbial
      progression for GlcNAc production from swollen chitin and chitosan by enzymatic
      degradation. Maximum chitinase (7.24+/-0.07U/ml) and chitosanase (8.42+/-0.09,
      8.51+/-0.25U/ml) enzyme activity were reached in submerged fermentation at an
      optimal pH of 7.0 and 30 degrees C. In this study, sucrose, yeast extract,
      (NH4)2SO4, and NaCl were found to be the potential enhancers of exo-chitinase
      activity and glucose, corn flour, yeast extract, soybean flour, (NH4)2SO4, NH4Cl
      and K2HPO4 were found to be the potential activator for exo-chitosanase activity.
      Optimum concentrations of the carbon sources for enhanced chitinase activity were
      9.91, 3.21, 9.86, 1.66U/ml and chitosanase activity were 1.63, 1.13, 2.28, 3.71,
      9.02, 4.93, and 2.14U/ml. These enzymes efficiently hydrolyzed swollen chitin and
      chitosan to N-acetylglucosamine were characterized by thin layer chromatography
      and were further confirmed by high-pressure liquid chromatography. From a
      commercial perspective, we isolated, optimized and characterized exochitinase
      from Escherichia fergusonii (HANDI 110) and chitosanase from Chryseobacterium
      indologenes (HANYOO), and Comamonas koreensis (HANWOO) for the large-scale
      production of GlcNAc facilitating its potential use in industrial applications.

PMID- 29452185
TI  - An injectable chitosan/chondroitin sulfate hydrogel with tunable mechanical
      properties for cell therapy/tissue engineering.
AB  - Chitosan (CH) hydrogels with remarkable mechanical properties and rapid gelation
      rate were recently synthesized by combining sodium hydrogen carbonate (SHC) with
      another weak base, such as beta-glycerophosphate (BGP). To improve their
      biological responses, in the present study, chondroitin sulfate (CS) was added to
      these CH hydrogels. Hydrogel characteristics in terms of pH and osmolarity, as
      well as rheological, mechanical, morphological and swelling properties, were
      studied in the absence and presence of CS. Effect of CS addition on
      cytocompatibility of hydrogels was also assessed by evaluating the viability and
      metabolic activity of encapsulated L929 fibroblasts. New CH hydrogels containing
      CS were thermosensitive and injectable with pH and osmolality close to
      physiological levels and enhanced swelling capacity. Encapsulated cells were able
      to maintain their viability and proliferative capacity up to 7 days and CS
      addition improved the viability of the cells, particularly in serum-free
      conditions. Addition of CS showed a reducing and dose-dependent effect on the
      mechanical strength of the hydrogels after complete gelation. This work provides
      evidence that CH-CS hydrogels prepared with a combination of SHC and BGP as a
      gelling agent have a promising potential to be used as thermosensitive,
      injectable and biocompatible matrices with tunable mechanical properties for cell
      therapy applications.

PMID- 29452186
TI  - Lectin obtained from the red seaweed Bryothamnion triquetrum: Secondary structure
      and anti-inflammatory activity in mice.
AB  - Seaweeds are sources of biomolecules with biological activities and
      pharmacological potential - for example, lectins, a group of proteins that can
      bind reversibly to carbohydrates or compounds containing them. The aim of this
      study was to elucidate the structural properties of a lectin extracted from the
      red seaweed Bryothamnion triquetrum (BtL) and to investigate its anti
      inflammatory activity in mice. The lectin was purified by precipitation with
      ammonium sulfate and ion-exchange chromatography. Its secondary structure and
      tryptophan (Trp) microenvironment were analyzed by circular dichroism
      spectroscopy and steady-state fluorescence spectroscopy, respectively. The anti
      inflammatory effect was evaluated by means of paw edema induced by carrageenan or
      dextran, myeloperoxidase activity in paw tissue, and by measurement of leukocyte
      and neutrophil migration and cytokine quantification in a peritonitis model. The
      secondary structure of BtL is mostly composed of beta-strands and unordered
      conformation, and it is quite resistant to extremes of pH and temperature,
      preserving the exposure of Trp residues under these conditions. In an assessment
      of biological activities, groups of mice were subjected to pretreatment with BtL
      before the inflammatory stimulus. BtL had anti-inflammatory effects in the models
      tested, and hence may be considered a molecule with potential to be used in the
      pharmaceutical industry.

PMID- 29452187
TI  - Purification of extra cellular poly-gamma-glutamic acid as an antibacterial agent
      using anion exchange chromatography.
AB  - BLAST analysis of the 16S rRNA gene sequence for the newly isolated bacterium,
      revealed significant identity (99.5%) with Bacillus sonorensis [Ijadi Bajestani,
      M., et al., International Journal of Biological Macromolecules, 2017. 96: p. 100
      110]. According to the literature review for closely related species of Bacillus
      sonorensis, the production of poly-gamma-glutamic acid (gamma-PGA) as an extra
      cellular biopolymer was investigated for the isolated bacteria which is deposited
      in IBRC (Iranian Biological Resource Center) as Bacillus sp. Strain M2 (IBRC
      M11173). To determine if gamma-PGA production by Bacillus sp. Strain M2 is
      glutamate dependent, it was grown on PGA medium, consisted of sodium glutamate.
      The results proved that gamma-PGA production is highly dependent on glutamate
      component. In the following, the bioproduct has undergone different purification
      processes mainly consisting of dialysis, deproteinization and anion exchange
      chromatography. Based on the high-performance liquid chromatography (HPLC)
      results for ion chromatography effluents, 59% of the initial PGA in main solution
      was eluted via NaCl elution. Gel permeation chromatography (GPC) characterization
      analysis was accomplished to determine the polydispersity and gamma-PGA molecular
      weight. Two major average molecular weights were distinguished; the heavy weight
      fraction of 7.7*106g/mol with polydispersity index of 1.73 and the other one with
      an average molecular weight number of 1.7*104g/mol and polydispersity index of
      4.4. The antibacterial activity of the extracellular gamma-PGA, as an anionic
      biopolymer, toward Staphylococcus aureus and E. coli, was assayed using the
      clinical and laboratory standards institute (CLSI) guidelines. For Staphylococcus
      aureus the minimum inhibitory concentration (MIC) value was about 34g/L while for
      E. coli this value reaches 53g/L.

PMID- 29452188
TI  - Phosphate fertilization changes the characteristics of 'Maca' banana starch.
AB  - The unripe banana has been studied as a potential source of starch for use in
      various applications. Considering the importance of phosphorus in the
      biosynthesis of the starch and also the interference of this mineral in starch
      properties, in this study it was evaluated the effect of rates of phosphate
      fertilizer applied in the cultivation of 'Maca' banana on the characteristics of
      the starch. Starches extracted from fruits from different treatments were
      analyzed for morphological characteristics, X-ray diffraction pattern, relative
      crystallinity, granule size, amylose, resistant starch and phosphorus levels, as
      well as, for pasting and thermal properties. Results showed that the phosphate
      fertilization has interference on the characteristics of the banana starch led to
      increase of phosphorus content and size of the granules, reduction of
      crystallinity and resistant starch content, decrease of viscosity peak,
      breakdown, final viscosity, setback, transitions temperatures and enthalpy. These
      changes caused by phosphate fertilizer conditions can be increase the
      applications of the 'Maca' banana starch.

PMID- 29452189
TI  - Roasted and green coffee extracts show antioxidant and cytotoxic activity in
      myoblast and endothelial cell lines in a cell specific manner.
AB  - Coffee is one of the most highly consumed beverages with potential beneficial
      health implications, however its molecular mechanism of action has not been
      completely elucidated yet. To that cause, the polyphenolic composition of
      different coffee extracts (from Light, Medium and Dark roasts as well as green
      beans) was examined by UHPLC-HRMS analysis, indicating chlorogenic acids isomers
      as the main constituents. In the following step, the toxicity of the extracts was
      tested in myoblasts and endothelial cells and differential toxicity of green and
      roasted samples was displayed as the myoblasts were more sensitive to green
      coffee extracts, in contrast to the endothelial cells. Subsequently, biologically
      relevant, non-cytotoxic extract concentrations were administered to explore their
      potential effect on cell redox status using flow cytometry and spectrophotometric
      assays. The results indicated that all coffee extracts improved cell redox
      status, however differences were observed between the two different cell lines
      tested, implying that coffee compounds display cell- and tissue-specificity.
      Glutathione levels were increased in almost all cases up to 70%, while the
      roasting degree affected the free radical scavenging potential of the extracts
      and their ability to protect from macromolecular oxidation as exhibited by the
      differences in ROS, CARB and TBARS levels, especially in the myoblasts.

PMID- 29452190
TI  - Toxicity assessment of mycotoxins extracted from contaminated commercial dog
      pelleted feed on canine blood mononuclear cells.
AB  - Raw ingredients of pet food are often contaminated with mycotoxins. This is a
      serious health problem to pets and causes emotional and economical stress to the
      pet owners. The aim of this study was to determine the immunotoxicity of the most
      common mycotoxins (aflatoxin, fumonisin, ochratoxin A and zearalenone) by
      examining 20 samples of extruded dry dog food found on the South African market
      [10 samples from standard grocery store lines (SB), 10 from premium veterinarian
      lines (PB)]. Pelleted dog food was subjected to extraction protocols optimized
      for the above mentioned mycotoxins. Dog lymphocytes were treated with the
      extracts (24 h incubation and final concentration 40 MUg/ml) to determine cell
      viability, mitochondrial function, oxidative stress, and markers of cell death
      using spectrophotometry, luminometry and flow cytometry. Malondialdehyde, a
      marker of oxidative stress showed no significant difference between SB and PB,
      however, GSH was significantly depleted in SB extract treatments. Markers of
      apoptosis (phosphatidylserine externalization) and necrosis (propidium iodide
      incorporation) were elevated in both food lines when compared to untreated
      control cells, interestingly SB extracts were significantly higher than PB. We
      also observed decreased ATP levels and increased mitochondrial depolarization in
      cells treated with both lines of feed with SB showing the greatest differences
      when compared to the control. This study provides evidence that irrespective of
      price, quality or marketing channels, pet foods present a high risk of mycotoxin
      contamination. Though in this study PB fared better than SB in regards to cell
      toxicity, there is a multitude of other factors that need to be studied which may
      have an influence on other negative outcomes.

PMID- 29452191
TI  - Recent advances of medical foods in China: The opportunities and challenges under
      standardization.
AB  - Malnutrition with high incidence in hospitalized patients in China has brought a
      significant burden of disease. Although many clinical studies have demonstrated
      the importance of nutritional for patients with malnutrition, the application of
      medical foods in China is still restricted. For the classification, limits,
      production and registration of medical foods, the Chinese government newly
      enacted a series of regulations. In this review, comparing the policy,
      researches, and product variety of medical foods in China with other countries,
      although the current status of the development of medical foods in China is still
      far behind that of developed countries, some of regulations are stricter than
      those of many other countries or organizations. The medical foods in China are
      divided into four categories, the nutrients and environmental contaminants are
      limited to ensure the safety. As a prospect, the development of medical foods in
      China is expected to get out of the predicament of lack of emphasis, shortage of
      supply, backward of local processing technology and the imperfect management
      system. After all, in view of the huge population and the increasing demand of
      nutrition in China, there must be a very good prospect for the future development
      of the medical foods industry in China.

PMID- 29452192
TI  - Graded 6-OHDA-induced dopamine depletion in the nigrostriatal pathway evokes
      progressive pathological neuronal activities in the subthalamic nucleus of a hemi
      parkinsonian mouse.
AB  - Recent studies have established methods for establishing a rodent model that
      mimics progressive stages of human Parkinson's disease (PD), via injection of
      graded doses of 6-hydroxydopamine (6-OHDA) into regions within the nigrostriatal
      pathway. However, the electrophysiological characteristics of the subthalamic
      nucleus (STN) in this model have not been fully elucidated in this model. This
      study aimed to investigate changes in the neuronal activity of the STN in a
      graded mouse model of PD. Increasing doses of 6-OHDA were unilaterally injected
      into the medial forebrain bundle (MFB) to produce a hemi-parkinsonian mouse
      model, mimicking early, moderate, advanced, and severe stages of human PD. Mice
      treated with higher doses of 6-OHDA demonstrated significantly lower rates of use
      of the impaired (contralateral) forelimb during wall contact, relative to sham
      mice. The STN firing rate was significantly increased in groups with >75%
      dopaminergic cell loss in the substantia nigra pars compacta (SNc), whereas
      little increase was observed in groups with partial lesions of the SNc, relative
      to the sham group. In addition, firing patterns of the STN in groups treated with
      higher doses of 6-OHDA became more irregular and exhibited burst-like patterns of
      activity, with dominant slow wave oscillations in the frequency range of 0.3-2.5
      Hz. Our results demonstrated a strong correlation between neuronal activities in
      the STN and dopamine depletion in the nigrostriatal pathway, which can be
      manipulated by variation of 6-OHDA doses.

PMID- 29452193
TI  - Antidepressant activity of vorinostat is associated with amelioration of
      oxidative stress and inflammation in a corticosterone-induced chronic stress
      model in mice.
AB  - Major depressive disorder (MDD) is a multifactorial neuropsychiatric disorder.
      Chronic administration of corticosterone (CORT) to rodents is used to mimic the
      stress associated dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis,
      a well-established feature found in depressive patients. Recently, preclinical
      studies have demonstrated the antidepressant potential of histone deacetylase
      (HDAC) inhibitors. So, we examined the antidepressant potential of vorinostat
      (VOR), a HDAC inhibitor against CORT injections in male mice. VOR (25 mg/kg;
      intraperitoneal) and fluoxetine (FLX) (15 mg/kg; oral) treatments were provided
      to CORT administered mice. At the end of dosing schedule, neurobehavioral tests
      were conducted; followed by mechanistic evaluation through biochemical analysis,
      RTPCR and western blot in serum and hippocampus. Neurobehavioral tests revealed
      the development of anxiety/depressive-like behavior in CORT mice as compared to
      the vehicle control. Depressive-mice showed concomitant HPA axis dysregulation as
      observed from the significant increase in serum CORT and ACTH. Chronic CORT
      administration was found to significantly increase hippocampal malondialdehyde
      (MDA) and iNOS levels while lowering glutathione (GSH) content, as compared to
      vehicle control. VOR treatment, in a similar manner to the classical
      antidepressant FLX, significantly ameliorated anxiety/depressive-like behavior
      along with HPA axis alterations induced by CORT. The antidepressant-like ability
      of drug treatments against chronic CORT induced stress model, as revealed in our
      study, may be due to their potential to mitigate inflammatory damage and
      oxidative stress via modulation of hippocampal NF-kappaB p65, COX-2, HDAC2 and
      phosphorylated JNK levels.

PMID- 29452194
TI  - Decompressive craniectomy protects against hippocampal edema and behavioral
      deficits at an early stage of a moderately controlled cortical impact brain
      injury model in adult male rats.
AB  - A decompressive craniectomy (DC) has been shown to be a life-saving therapeutic
      treatment for traumatic brain injury (TBI) patients, which also might result in
      post-operative behavioral dysfunction. However, there is still no definite
      conclusion about whether the behavioral dysfunction already existed at an early
      stage after the DC operation or is just a long-term post-operation complication.
      Therefore, the aim of the present study was to analyze whether DC treatment was
      beneficial to behavioral function at an early stage post TBI. In this study, we
      established a controlled cortical impact injury rat model to evaluate the
      therapeutic effect of DC treatment on behavioral deficits at 1 d, 2 d, 3 d and 7
      d after TBI. Our results showed that rats suffered significant behavioral and
      mood deficits after TBI compared to the control group, while decompressive
      craniectomy treatment could normalize MMP-9 expression levels and reduce
      hippocampal edema formation, stabilize the expression of Synapsin I, which was a
      potential indicator of maintaining the hippocampal synaptic function, thus
      counteracting behavioral but not mood decay in rats subjected to TBI. In
      conclusion, decompressive craniectomy, excepting for its life-saving effect,
      could also play a potential beneficial neuroprotective role on behavioral but not
      mood deficits at an early stage of moderate traumatic brain injury in rats.

PMID- 29452195
TI  - Construction and evaluation of the immune protection of a recombinant divalent
      protein composed of the MrpA from MR/P fimbriae and flagellin of Proteus
      mirabilis strain against urinary tract infection.
AB  - Urinary tract infections (UTI) caused by Proteus mirabilis are prevalent among
      the catheterized patients. There is no effective vaccine to reduce the frequency
      of UTIs caused by P. mirabilis. In the present study, the immune responses and
      effectiveness of different combinations of MrpA and flagellin (FliC) of P.
      mirabilis were assessed intranasally in the mice model. The addition of FliC as
      adjuvant to MrpA in fusion form significantly raised the mucosal IgA and cellular
      (IFN-gamma and IL-17) responses and maintained the serum IgG responses for 180
      days after the first vaccination. Furthermore, MrpA in fusion form with FliC
      significantly increased the systemic, mucosal and IFN-gamma responses of the FliC
      alone. In a bladder challenge assay with P. mirabilis, the fusion MrpA.FliC and
      the mixture of MrpA and FliC significantly decreased the colony count of the
      bacteria in the bladder and kidneys of mice in comparison to the control mice. It
      suggests a complex of the systemic, mucosal and cellular responses are needed for
      protection of the bladder and kidneys against P. mirabilis UTI. In our knowledge,
      the adjuvant property of the recombinant P. mirabilis flagellin was evaluated for
      the first time in a vaccine combination administered by an intranasal route. Our
      results suggest the recombinant flagellin of P. mirabilis could be used as an
      intranasal adjuvant in combination with other potential antigens against UTIs.

PMID- 29452196
TI  - Staphylococcus aureus induces TGF-beta1 and bFGF expression through the
      activation of AP-1 and NF-kappaB transcription factors in bovine mammary
      epithelial cells.
AB  - Staphylococcus aureus is a common Gram-positive pathogen that causes bovine
      mastitis, a persistent infection of the bovine mammary gland. Bovine mammary
      epithelial cells (BMEC) are important parenchymal cells of the bovine mammary
      gland. To better understand the importance of BMEC and the roles of the TLR-NF
      kappaBand TLR-AP-1 signaling pathways in the regulation of S. aureus-associated
      mastitis and mammary fibrosis, BMEC cultured in vitro were stimulated with
      different concentrations of heat-inactivated S. aureus to analyze the gene and
      protein expression and production of toll-like receptor 2 (TLR2), toll-like
      receptor 4 (TLR4), transforming growth factor beta 1 (TGF-beta1), basic
      fibroblast growth factor (bFGF) as well as the protein expression of nuclear
      factor-kappa B (NF-kappaB) and activation protein-1 (AP-1) by means of
      quantitative polymerase chain reaction (qPCR) and western blotting, respectively.
      Specific NF-kappaB and AP-1 inhibitors were also used to investigate their
      effects on the regulation of TGF-beta1 and bFGF expression. The results indicated
      that, in addition to increasing mRNA expression and secretion of TLR2 and TLR4,
      S. aureus could also upregulate TGF-beta1 and bFGF mRNA expression and secretion
      through the activation of NF-kappaB and AP-1. The increase in TGF-beta1 and bFGF
      expression was shown to be inhibited by AP-1- and NF-kappaB-specific inhibitors.
      Taken together, S. aureus induces TGF-beta1 and bFGF expression through the
      activation of AP-1 and NF-kappaB in BMECs. This information offers new potential
      targets for the treatment of bovine mammary fibrosis.

PMID- 29452197
TI  - Essential oils from Origanum vulgare and Salvia officinalis exhibit antibacterial
      and anti-biofilm activities against Streptococcus pyogenes.
AB  - In the present study, essential oils (EOs) extracted from oregano, sage, cloves,
      and ginger were evaluated for the phytochemical profile, antibacterial, and anti
      biofilm activities against Streptococcus pyogenes. The broth microdilution method
      was used to determine the minimal inhibitory concentration (MIC) and minimal
      bactericidal concentration (MBC) of EOs. The minimum biofilm inhibitory
      concentrations (MBICs) were determined using MTT assay and fixed biofilms were
      observed through scan electron microscopy. The oregano and sage EOs showed the
      lowest MIC as well as MBC of 0.25-0.5 mg/mL. Time kill assay results showed that
      oregano and sage EOs exhibited bactericidal effects within 5 min and 4 h,
      respectively. Both oregano and sage extracts acts as a potent anti-biofilm agent
      with dual actions, preventing and eradicating the biofilm. The microscopic
      visualization of biofilms treated with EOs have shown morphological and density
      changes compared to the untreated control. Oregano EO was constituted
      predominantly carvacrol (91.6%) and in sage EO, higher levels of alpha-thujone
      (28.5%) and camphor (16.6%) were revealed. EOs of oregano and sage inhibit the
      growth and biofilm formation of S. pyogenes. Effective concentrations of oregano
      and sage EOs and their phytochemicals can be used in developing potential plant
      derived antimicrobial agents in the management of streptococcal pharyngitis.

PMID- 29452198
TI  - Microbial infection pattern, pathogenic features and resistance mechanism of
      carbapenem-resistant Gram negative bacilli during long-term hospitalization.
AB  - BACKGROUND: Carbapenem-resistant Gram-negative bacilli (GNB) have become an
      important cause of nosocomial infections of hospitalized patients. METHODS: To
      investigate the microbial infection patterns and molecular epidemiology
      characteristics of the carbapenem-resistant GNB isolates from a long-term
      hospitalized patient, antimicrobial susceptibility testing, phenotypic screening
      test for carbapenemase production, PCR screening and DNA sequencing of
      carbapenemase genes, repetitive extragenic palindromic sequence-based PCR (REP
      PCR), multilocus sequencing typing (MLST) and genetic environment analysis were
      performed. RESULTS: Twelve strains with carbapenemase genes were detected from 63
      carbapenem-resistant isolates, including two blaIMP-25-carrying Pseudomonas
      aeruginosa, one blaNDM-1-carrying Citrobacter freundii, three blaNDM-1-carrying
      Klebsiella pneumoniae and six blaKPC-2-carrying K. pneumoniae. Only the blaNDM-1
      genes were successfully transferred from three K. pneumoniae strains to
      Escherichia coli C600 by conjugation. Genetic environment of blaIMP-25, blaNDM-1
      and blaKPC-2 genes in our study were consistent with previous reports. Molecular
      typing of K. pneumoniae performed by MLST revealed that most of the isolates
      belonged to ST11. blaNDM-1-carrying K. pneumoniae sequencing type 1416 was first
      reported in our study. CONCLUSIONS: Carbapenem-resistant GNB are common pathogens
      during long-term hospitalization, and ST11 blaKPC-2-carrying K. pneumoniae is the
      dominant bacterium in our study. Colonization and horizontal transmission of
      resistance by plasmids of carbapenem-resistant GNB have increased the risks of
      persistent infection and mortality of long-term hospitalized patients.

PMID- 29452200
TI  - Identification of clinically relevant chronic rhinosinusitis endotypes using
      cluster analysis of mucus cytokines.

PMID- 29452201
TI  - The nasal microbiome in patients with chronic rhinosinusitis: Analyzing the
      effects of atopy and bacterial functional pathways in 111 patients.

PMID- 29452199
TI  - Establishment of the nasal microbiota in the first 18 months of life: Correlation
      with early-onset rhinitis and wheezing.
AB  - BACKGROUND: Dynamic establishment of the nasal microbiota in early life
      influences local mucosal immune responses and susceptibility to childhood
      respiratory disorders. OBJECTIVE: The aim of this case-control study was to
      monitor, evaluate, and compare development of the nasal microbiota of infants
      with rhinitis and wheeze in the first 18 months of life with those of healthy
      control subjects. METHODS: Anterior nasal swabs of 122 subjects belonging to the
      Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort were
      collected longitudinally over 7 time points in the first 18 months of life. Nasal
      microbiota signatures were analyzed by using 16S rRNA multiplexed pair-end
      sequencing from 3 clinical groups: (1) patients with rhinitis alone (n = 28), (2)
      patients with rhinitis with concomitant wheeze (n = 34), and (3) healthy control
      subjects (n = 60). RESULTS: Maturation of the nasal microbiome followed
      distinctive patterns in infants from both rhinitis groups compared with control
      subjects. Bacterial diversity increased over the period of 18 months of life in
      control infants, whereas infants with rhinitis showed a decreasing trend (P <
      .05). An increase in abundance of the Oxalobacteraceae family (Proteobacteria
      phylum) and Aerococcaceae family (Firmicutes phylum) was associated with rhinitis
      and concomitant wheeze (adjusted P < .01), whereas the Corynebacteriaceae family
      (Actinobacteria phylum) and early colonization with the Staphylococcaceae family
      (Firmicutes phylum; 3 weeks until 9 months) were associated with control subjects
      (adjusted P < .05). The only difference between the rhinitis and control groups
      was a reduced abundance of the Corynebacteriaceae family (adjusted P < .05).
      Determinants of nasal microbiota succession included sex, mode of delivery,
      presence of siblings, and infant care attendance. CONCLUSION: Our results support
      the hypothesis that the nasal microbiome is involved in development of early
      onset rhinitis and wheeze in infants.

PMID- 29452202
TI  - Effectiveness of indoor allergen reduction in asthma management: A systematic
      review.
AB  - BACKGROUND: This review will inform updated National Asthma Education and
      Prevention Program clinical practice guidelines. OBJECTIVE: We sought to evaluate
      the effectiveness of allergen reduction interventions on asthma outcomes.
      METHODS: We systematically searched the "gray literature" and 5 bibliographic
      databases. Eligible studies included systematic reviews, randomized controlled
      trials, and nonrandomized interventional studies. Risk of bias was assessed by
      using the Cochrane Risk of Bias instrument and the Newcastle-Ottawa scale. The
      evidence base was assessed by using the approach of the Agency for Healthcare
      Research and Quality's Evidence-based Practice Center program. RESULTS: Fifty
      nine randomized and 8 nonrandomized trials addressed 8 interventions: acaricide,
      air purification, carpet removal, high-efficiency particulate air filtration
      (HEPA) vacuums, mattress covers, mold removal, pest control, and pet removal.
      Thirty-seven studies evaluated single-component interventions, and 30 studies
      assessed multicomponent interventions. Heterogeneity precluded meta-analysis. For
      most interventions and outcomes, the evidence base was inconclusive or showed no
      effect. No interventions were associated with improvement in validated asthma
      control measures or pulmonary physiology. Exacerbations were diminished in
      multicomponent studies that included HEPA vacuums or pest control (moderate
      strength of evidence [SOE] for both). Quality of life improved in studies of air
      purifiers (SOE: low) and in multicomponent studies that included HEPA vacuums
      (SOE: moderate) or pest control (SOE: low). CONCLUSIONS: Single interventions
      were generally not associated with improvement in asthma measures, with most
      strategies showing inconclusive results or no effect. Multicomponent
      interventions improved various outcomes, but no combination of specific
      interventions appears to be more effective. The evidence was often inconclusive
      because of a lack of studies. Further research is needed comparing the effect of
      indoor allergen reduction interventions on validated asthma measures, with
      sufficient population sizes to detect clinically meaningful differences.

PMID- 29452203
TI  - Morphology of the elytral base sclerites.
AB  - The elytral base sclerites (= sclerites located at the articular region between
      the forewing and thorax in Coleoptera) of selected taxa were examined and
      homologized. Although the elytral base sclerites are highly modified compared to
      the wing base sclerites of the other neopterans, they can be homologized by using
      the conservative wing flapping and folding lines as landmarks. A reduction of the
      first axillary sclerite was identified as a general trend of the elytral base
      sclerites, although the sclerite usually has a very important function to mediate
      flight power from the notum to the wing. This result indicates that the
      functional constraint against the basal sclerites is relaxed because of the lack
      of an ability to produce flight power by elytra. In contrast, the elytral folding
      system formed by the basal sclerites is well retained, which probably occurs
      because proper wing folding is a key for the shelter function of the elytra. The
      elytral base sclerites apparently contain more homoplasies than the serially
      homologous hindwing base sclerites of Coleoptera, which suggests that the
      structure is less useful for higher-level systematics. However, the faster
      evolutionary rate of the elytral base sclerites suggests there is potential for
      studying the lower-level phylogeny of Coleoptera.

PMID- 29452204
TI  - Antiviral therapy in hepatitis B virus-infected children with immune-tolerant
      characteristics: A pilot open-label randomized study.
AB  - BACKGROUND & AIM: Chronic infection with hepatitis B virus (HBV) in children is a
      serious health problem worldwide. How to treat children with immune-tolerant
      chronic hepatitis B infection, commonly characterized by hepatitis B e antigen
      (HBeAg) positivity, high viral load, normal or mildly elevated alanine
      aminotransferase and no or minimal inflammation in liver histology, remains
      unresolved. This trial aims to study the benefits of antiviral therapy in
      children with these characteristics. METHODS: This is a pilot open-label
      randomized controlled study. From May 2014 to April 2015, 69 treatment-naive
      chronically HBV-infected children, aged 1 to 16 years, who had immune-tolerant
      characteristics were recruited to this trial and randomly assigned, in a 2:1
      ratio, to treatment group and control group. Patients in the treatment group
      received either interferon-alpha (IFN) monotherapy or consecutively received IFN
      monotherapy, combination therapy of IFN and lamivudine (LAM), and LAM therapy
      alone. All patients were observed until week 96. RESULTS: At baseline,
      epidemiological, biochemical, serological, virological and histological indices
      were consistent across the treatment and control groups. Of the 46 patients in
      the treatment group, 73.91% had undetectable serum HBV DNA, 32.61% achieved HBeAg
      seroconversion and 21.74% lost hepatitis B surface antigen (HBsAg) at the
      endpoint. No LAM resistance emerged at week 96. In the control group, only one
      (4.35%) patient underwent spontaneous HBeAg seroconversion and had undetectable
      serum HBV DNA during observation, and moreover, none developed HBsAg clearance.
      For all patients, no serious adverse events were observed. CONCLUSION: Antiviral
      treatment with a sequential combination of IFN and LAM resulted in a significant
      improvement in the rates of undetectable serum HBV DNA, HBeAg seroconversion and
      HBsAg loss in children with chronic HBV infection and immune-tolerant
      characteristics. LAY SUMMARY: There is a lack of data regarding treatment of
      immune-tolerant chronic hepatitis B (CHB). It remains unresolved how children
      with immune-tolerant CHB should be treated. This paper reports the outcomes from
      a pilot open-label randomized controlled trial on antiviral therapy in children
      with immune-tolerant characteristics. It shows that a sequential combination of
      interferon-alpha and lamivudine was beneficial.

PMID- 29452205
TI  - Impaired cerebral microcirculation induced by ammonium chloride in rats is due to
      cortical adenosine release.
AB  - BACKGROUND & AIMS: Liver failure results in hyperammonaemia, impaired regulation
      of cerebral microcirculation, encephalopathy, and death. However, the key
      mediator that alters cerebral microcirculation remains unidentified. In this
      study we show that topically applied ammonium significantly increases
      periarteriolar adenosine tone on the brain surface of healthy rats and is
      associated with a disturbed microcirculation. METHODS: Cranial windows were
      prepared in anaesthetized Wistar rats. The flow velocities were measured by
      speckle contrast imaging and compared before and after 30 min of exposure to 10
      mM ammonium chloride applied on the brain surface. These flow velocities were
      compared with those for control groups exposed to artificial cerebrospinal fluid
      or ammonium plus an adenosine receptor antagonist. A flow preservation curve was
      obtained by analysis of flow responses to a haemorrhagic hypotensive challenge
      and during stepwise exsanguination. The periarteriolar adenosine concentration
      was measured with enzymatic biosensors inserted in the cortex. RESULTS: After
      ammonium exposure the arteriolar flow velocity increased by a median
      (interquartile range) of 21.7% (23.4%) vs. 7.2% (10.2%) in controls (n = 10 and n
      = 6, respectively, p <0.05), and the arteriolar surface area increased. There was
      a profound rise in the periarteriolar adenosine concentration. During the
      hypotensive challenge the flow decreased by 27.8% (14.9%) vs. 9.2% (14.9%) in
      controls (p <0.05). The lower limit of flow preservation remained unaffected,
      27.7 (3.9) mmHg vs. 27.6 (6.4) mmHg, whereas the autoregulatory index increased,
      0.29 (0.33) flow units per millimetre of mercury vs. 0.03 (0.21) flow units per
      millimetre of mercury (p <0.05). When ammonium exposure was combined with topical
      application of an adenosine receptor antagonist, the autoregulatory index was
      normalized. CONCLUSIONS: Vasodilation of the cerebral microcirculation during
      exposure to ammonium chloride is associated with an increase in the adenosine
      tone. Application of a specific adenosine receptor antagonist restores the
      regulation of the microcirculation. This indicates that adenosine could be a key
      mediator of the brain dysfunction seen during hyperammonaemia and is a potential
      therapeutic target. LAY SUMMARY: In patients with liver failure, disturbances in
      brain function are caused in part by ammonium toxicity. In our project we studied
      how ammonia, through adenosine release, affects the blood flow in the brain of
      rats. In our experimental model we demonstrated that the detrimental effect of
      ammonia on blood flow regulation was counteracted by blocking the adenosine
      receptors in the brain. With this observation we identified a novel potential
      treatment target. If we can confirm our findings in a future clinical study, this
      might help patients with liver failure and the severe condition called hepatic
      encephalopathy.

PMID- 29452206
TI  - SNX10 mediates alcohol-induced liver injury and steatosis by regulating the
      activation of chaperone-mediated autophagy.
AB  - BACKGROUND & AIMS: Alcoholic liver disease (ALD) is a major cause of morbidity
      and mortality worldwide. However, the cellular defense mechanisms underlying ALD
      are not well understood. Recent studies highlighted the involvement of chaperone
      mediated autophagy (CMA) in regulating hepatic lipid metabolism. Sorting nexin
      (SNX)-10 has a regulatory function in endolysosomal trafficking and
      stabilisation. Here, we investigated the roles of SNX10 in CMA activation and in
      the pathogenesis of alcohol-induced liver injury and steatosis. METHODS: Snx10
      knockout (Snx10 KO) mice and their wild-type (WT) littermates fed either the
      Lieber-DeCarli liquid alcohol diet or a control liquid diet, and primary cultured
      WT and Snx10 KO hepatocytes stimulated with ethanol, were used as in vivo and in
      vitro ALD models, respectively. Activation of CMA, liver injury parameters,
      inflammatory cytokines, oxidative stress and lipid metabolism were measured.
      RESULTS: Compared with WT littermates, Snx10 KO mice exhibited a significant
      amelioration in ethanol-induced liver injury and hepatic steatosis. Both in vivo
      and in vitro studies showed that SNX10 deficiency upregulated lysosome-associated
      membrane protein type 2A (LAMP-2A) expression and CMA activation, which could be
      reversed by SNX10 overexpression in vitro. LAMP-2A interference confirmed that
      the upregulation of Nrf2 and AMPK signalling pathways induced by SNX10 deficiency
      relied on CMA activation. Pull-down assays revealed an interaction between SNX10
      and cathepsin A (CTSA), a key enzyme involved in LAMP-2A degradation. Deficiency
      in SNX10 inhibited CTSA maturation and increased the stability of LAMP-2A,
      resulting in an increase in CMA activity. CONCLUSIONS: SNX10 controls CMA
      activity by mediating CTSA maturation, and, thus, has an essential role in
      alcohol-induced liver injury and steatosis. Our results provide evidence for
      SNX10 as a potential promising therapeutic target for preventing or ameliorating
      liver injury in ALD. LAY SUMMARY: Alcoholic liver disease is a major cause of
      morbidity and mortality worldwide. Recent studies highlight the involvement of
      chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Our
      study reveals that deficiency of sorting nexin (SNX) 10 increases the stability
      of LAMP-2A by inhibiting cathepsin A maturation, resulting in the increase of CMA
      activity and, thus, alleviates alcohol-induced liver injury and steatosis.

PMID- 29452207
TI  - Glycogen synthase kinase 3beta promotes liver innate immune activation by
      restraining AMP-activated protein kinase activation.
AB  - BACKGROUND & AIMS: Glycogen synthase kinase 3beta (Gsk3beta [Gsk3b]) is a
      ubiquitously expressed kinase with distinctive functions in different types of
      cells. Although its roles in regulating innate immune activation and ischaemia
      and reperfusion injuries (IRIs) have been well documented, the underlying
      mechanisms remain ambiguous, in part because of the lack of cell-specific tools
      in vivo. METHODS: We created a myeloid-specific Gsk3b knockout (KO) strain to
      study the function of Gsk3beta in macrophages in a murine liver partial warm
      ischaemia model. RESULTS: Compared with controls, myeloid Gsk3b KO mice were
      protected from IRI, with diminished proinflammatory but enhanced anti
      inflammatory immune responses in livers. In bone marrow-derived macrophages,
      Gsk3beta deficiency resulted in an early reduction of Tnf gene transcription but
      sustained increase of Il10 gene transcription on Toll-like receptor 4 stimulation
      in vitro. These effects were associated with enhanced AMP-activated protein
      kinase (AMPK) activation, which led to an accelerated and higher level of
      induction of the novel innate immune negative regulator small heterodimer partner
      (SHP [Nr0b2]). The regulatory function of Gsk3beta on AMPK activation and SHP
      induction was confirmed in wild-type bone marrow-derived macrophages with a Gsk3
      inhibitor. Furthermore, we found that this immune regulatory mechanism was
      independent of Gsk3beta Ser9 phosphorylation and the phosphoinositide 3-kinase
      Akt signalling pathway. In vivo, myeloid Gsk3beta deficiency facilitated SHP
      upregulation by ischaemia-reperfusion in liver macrophages. Treatment of Gsk3b KO
      mice with either AMPK inhibitor or SHP small interfering RNA before the onset of
      liver ischaemia restored liver proinflammatory immune activation and IRI in these
      otherwise protected hosts. Additionally, pharmacological activation of AMPK
      protected wild-type mice from liver IRI, with reduced proinflammatory immune
      activation. Inhibition of the AMPK-SHP pathway by liver ischaemia was
      demonstrated in tumour resection patients. CONCLUSIONS: Gsk3beta promotes innate
      proinflammatory immune activation by restraining AMPK activation. LAY SUMMARY:
      Glycogen synthase kinase 3beta promotes macrophage inflammatory activation by
      inhibiting the immune regulatory signalling of AMP-activated protein kinase and
      the induction of small heterodimer partner. Therefore, therapeutic targeting of
      glycogen synthase kinase 3beta enhances innate immune regulation and protects
      liver from ischaemia and reperfusion injury.

PMID- 29452208
TI  - Outcome of ABO-incompatible adult living-donor liver transplantation for patients
      with hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Living-donor liver transplantation (LDLT) can simultaneously
      cure hepatocellular carcinoma (HCC) and underlying liver cirrhosis, improving
      long-term results in patients with HCC. ABO-incompatible LDLT could expand the
      living-donor pool, reduce waiting times for deceased-donor liver transplantation,
      and improve long-term survival for some patients with HCC. METHODS: We
      retrospectively reviewed the medical records of patients undergoing LDLT for HCC
      from November 2008 to December 2015 at a single institution in Korea. In total,
      165 patients underwent ABO-incompatible and 753 patients underwent ABO-compatible
      LDLT for HCC. ABO-incompatible recipients underwent desensitization to overcome
      the ABO blood group barrier, including pretransplant plasma exchange and
      rituximab administration (300-375 mg/m2 /body surface area). RESULTS: We
      performed 1:1 propensity score matching and included 165 patients in each group.
      82.4% of ABO-incompatible and 83.0% of -compatible LDLT groups had HCC within
      conventional Milan criteria, respectively, and 92.1% and 92.7% of patients in
      each group had a Child-Pugh score of A or B. ABO-incompatible and -compatible
      LDLT groups were followed up for 48.0 and 48.7 months, respectively, with both
      groups showing comparable recurrence-free survival rates (hazard ratio [HR] 1.14;
      95% CI 0.68-1.90; p = 0.630) and overall patient-survival outcomes (HR 1.10; 95%
      CI 0.60-2.00; p = 0.763). CONCLUSIONS: These findings suggested that ABO
      incompatible liver transplantation is a feasible option for patients with HCC,
      especially for those with compensated cirrhosis with HCC within conventional
      Milan criteria. LAY SUMMARY: Despite hypothetical immunological concerns that the
      desensitization protocol for breaking through the ABO blood group barrier might
      have a negative impact on the recurrence of hepatocellular carcinoma, our
      experience demonstrated no significant differences in the long-term overall
      survival and recurrence-free survival rates between patients receiving ABO
      compatible or ABO-incompatible liver transplantation. In conclusion, results from
      our institution indicated that ABO-incompatible living-donor liver
      transplantation constitutes a potentially feasible option for patients with
      hepatocellular carcinoma, especially those with compensated cirrhosis with
      hepatocellular carcinoma within conventional Milan criteria.

PMID- 29452209
TI  - Prolactin improves hepatic steatosis via CD36 pathway.
AB  - BACKGROUND & AIMS: Prolactin (PRL) is a multifunctional polypeptide with effects
      on metabolism, however, little is known about its effect on hepatic steatosis and
      lipid metabolism. Herein, we aimed to assess the role of PRL in the development
      of non-alcoholic fatty liver disease (NAFLD). METHODS: The serum PRL levels of
      456 patients with NAFLD, 403 controls without NAFLD diagnosed by ultrasound, and
      85 individuals with liver histology obtained during metabolic surgery (44 female
      and 30 male patients with NAFLD and 11 age-matched non-NAFLD female individuals)
      were evaluated. The expression of the gene encoding the prolactin receptor (PRLR)
      and signalling molecules involved in hepatic lipid metabolism were evaluated in
      human liver and HepG2 cells. The effects of overexpression of PRLR or fatty acid
      translocase (FAT)/CD36 or knockdown of PRLR on hepatic lipid metabolism were
      tested in free fatty acid (FFA)-treated HepG2 cells. RESULTS: Circulating PRL
      levels were lower in individuals with ultrasound-diagnosed NAFLD (men: 7.9
      [range, 5.9-10.3] ug/L; women: 8.7 [range, 6.1-12.4] ug/L) than those with non
      NAFLD (men: 9.1 [range, 6.8-13.0] ug/L, p = 0.002; women: 11.6 [range, 8.2-16.1]
      ug/L, p <0.001). PRL levels in patients with biopsy-proven severe hepatic
      steatosis were lower compared with those with mild-to-moderate hepatic steatosis
      in both men (8.3 [range, 5.4-9.5] ug/L vs. 9.7 [range, 7.1-12.3] ug/L, p = 0.031)
      and women (8.5 [range, 4.2-10.6] ug/L vs. 9.8 [range, 8.2-15.7] ug/L, p = 0.027).
      Furthermore, hepatic PRLR gene expression was significantly reduced in patients
      with NAFLD and negatively correlated with CD36 gene expression. In FFA-induced
      HepG2 cells, PRL treatment or PRLR overexpression significantly reduced the
      expression of CD36 and lipid content, effects that were abrogated after silencing
      of PRLR. Furthermore, overexpression of CD36 significantly reduced the PRL
      mediated improvement in lipid content. CONCLUSIONS: Our results reveal a novel
      association between the central nervous system and the liver, whereby PRL/PRLR
      improved hepatic lipid accumulation via the CD36 pathway. LAY SUMMARY: Our
      clinical study suggests a negative association between prolactin (PRL)/prolactin
      receptor (PRLR) and the presence of non-alcoholic fatty liver disease (NAFLD).
      Using cell experiments, we found that PRL ameliorates hepatic steatosis via the
      hepatic PRLR and fatty acid translocase (FAT)/CD36, a key transporter of free
      fatty acid uptake in liver. Our findings suggest a novel approach to improving
      NAFLD using PRL and PRLR. Clinical trial number: NCT03296605.

PMID- 29452210
TI  - Computer simulations for bioequivalence trials: Selection of analyte in BCS class
      II and IV drugs with first-pass metabolism, two metabolic pathways and intestinal
      efflux transporter.
AB  - A semi-physiological two compartment pharmacokinetic model with two active
      metabolites (primary (PM) and secondary metabolites (SM)) with saturable and non
      saturable pre-systemic efflux transporter, intestinal and hepatic metabolism has
      been developed. The aim of this work is to explore in several scenarios which
      analyte (parent drug or any of the metabolites) is the most sensitive to changes
      in drug product performance (i.e. differences in in vivo dissolution) and to make
      recommendations based on the simulations outcome. A total of 128 scenarios (2
      Biopharmaceutics Classification System (BCS) drug types, 2 levels of KM Pgp, in 4
      metabolic scenarios at 2 dose levels in 4 quality levels of the drug product)
      were simulated for BCS class II and IV drugs. Monte Carlo simulations of all
      bioequivalence studies were performed in NONMEM 7.3. Results showed the parent
      drug (PD) was the most sensitive analyte for bioequivalence trials in all the
      studied scenarios. PM and SM revealed less or the same sensitivity to detect
      differences in pharmaceutical quality as the PD. Another relevant result is that
      mean point estimate of Cmax and AUC methodology from Monte Carlo simulations
      allows to select more accurately the most sensitive analyte compared to the
      criterion on the percentage of failed or successful BE studies, even for
      metabolites which frequently show greater variability than PD.

PMID- 29452211
TI  - Impact of change of matrix crystallinity and polymorphism on ovalbumin release
      from lipid-based implants.
AB  - The objectives of this study were to prepare lipid-based implants by hot melt
      extrusion (HME) for the prolonged release of ovalbumin (OVA), and to relate
      protein release to crystallinity and polymorphic changes of the lipid matrix. Two
      lipids, glycerol tristearate and hydrogenated palm oil, with different
      composition and degree of crystallinity were studied. Solid OVA was dispersed
      within the lipid matrixes, which preserved its stability during extrusion. This
      was partially attributed to a protective effect of the lipidic matrix. The
      incorporation of OVA decreased the mechanical strength of the implants prepared
      with the more crystalline matrix, glycerol tristearate, whereas it remained
      comparable for the hydrogenated palm oil because of stronger physical and non
      covalent interactions between the protein and this lipid. This was also the
      reason for the faster release of OVA from the glycerol tristearate matrix when
      compared to the hydrogenated palm oil (8 vs. 28 weeks). Curing induced and
      increased crystallinity, and changes in the release rate, especially for the more
      crystalline matrix. In this case, both an increase and a decrease in release,
      were observed depending on the tempering condition. Curing at higher temperatures
      induced a melt-mediated crystallization and solid state transformation of the
      glycerol tristearate matrix and led to rearrangements of the inner structure with
      the formation of larger pores, which accelerated the release. In contrast,
      changes in the hydrogenated palm oil under the same curing conditions were less
      noticeable leading to a more robust formulation, because of less polymorphic
      changes over time. This study helps to understand the effect of lipid matrix
      composition and crystallinity degree on the performance of protein-loaded
      implants, and to establish criteria for the selection of a lipid carrier
      depending on the release profile desired.

PMID- 29452212
TI  - Exploring in vivo metabolism and excretion of QO-58L using ultra-high-performance
      liquid chromatography coupled with tandem mass spectrometry.
AB  - QO-58 lysine (QO-58L) as a new potassium channel opener, reported to have a
      potential activity to cure neuropathic pain. The aim of this research is to
      develop and validate a high-performance liquid chromatography with tandem
      spectrometry (LC-MS/MS) method for the quantification of QO-58L in rat urine,
      feces and bile. In addition, analyze and identify the metabolites in urine and
      bile. The assay for this compound in samples detected with multiple reaction
      monitoring mode (MRM), and take nimodipine as internal standards (IS). To better
      understand the biotransformation of QO-58L, metabolites in urine and bile were
      identified by using ultra high performance liquid chromatography tandem
      quadrupole/time of flight mass spectrometry (UHPLC-Q-TOF-MS) in the positive and
      negative ion mode. Urine, feces and bile were quantified by three new methods.
      The results showed that: QO-58L was mainly eliminated through fecal route
      (92.94%), a small amount of it via biliary excretion (2.05%), and rarely through
      urinary excretion (0.024%). As a result, there are 11 metabolites were
      identified, including 8 phase I metabolites resulting from elimination,
      hydroxylation and dihydroxylation, and 3 phase II metabolites originating from
      sulfation, N-acetylcysteine conjugation and glucuronidation. Furthermore, the
      newly discoveries of excretion and metabolism significantly expanded our
      understanding and was going to be greatly helpful for QO-58L's further
      pharmacokinetic study in vivo.

PMID- 29452213
TI  - Nanoemulsion of atovaquone as a promising approach for treatment of acute and
      chronic toxoplasmosis.
AB  - Treatment of toxoplasmosis is necessary in congenital form and immunocompromised
      patients. Atovaquone is a powerful suppressor of protozoan parasites with a broad
      spectrum activity, but an extremely low water solubility and bioavailability. In
      this study, nanoemulsion of this drug was prepared with grape seed oil using
      spontaneous emulsification method to increase bioavailability and efficacy of
      atovaquone for treatment of toxoplasmosis. In vitro activity of atovaquone
      nanoemulsion against T. gondii, RH and Tehran strains, was assessed in HeLa cell
      culture. For in vivo assessment, BALB/c mice were infected with RH and Tehran
      strains and then treated with nanoemulsion of atovaquone, compared to that
      treated with free atovaquone. Concentration of atovaquone nanoemulsion showed in
      vitro anti-parasitic effects in both strains of T. gondii. Furthermore, oral
      administration of atovaquone nanoemulsion increased oral bioavailability, tissue
      distribution and mice survival time and reduced parasitemia and number and size
      of the brain cysts. Decrease of cyst numbers was verified by down regulation of
      BAG1 using real-time polymerase chain reaction (real-time PCR) assay. Effective
      therapeutic activity of atovaquone at a reduced dose is the major achievement of
      this study.

PMID- 29452214
TI  - Progranulin promotes lymphangiogenesis through VEGF-C and is an independent risk
      factor in human esophageal cancers.
AB  - Lymph node metastasis is one of the most important predictors of the prognosis
      for esophageal cancer (EC) patients. However, the mechanism underlying the lymph
      node metastasis is largely unknown. Progranulin (PGRN) is shown to be highly
      expressed in various types of cancers and could promote the angiogenesis and
      epithelial-mesenchymal transition of cancer cells in previous studies. However,
      the expression status of PGRN and its effects on the lymphangiogenesis in EC are
      largely unclear. In this study, we show for the first time that PGRN is expressed
      in EC tissue samples and cell lines and could promote the expression of VEGF-C in
      vitro, a well-known lymphangiogenesis inducer, through the putative signaling
      transducers p-ERK and p-AKT. Besides, increased levels of PGRN are correlated
      with lymph node metastasis, high levels of lymph microvessel density, and lymph
      vessel space invasion in tissue samples of EC patients. In addition, Cox
      proportional risk model shows that patients with high levels of PGRN would have 2
      fold increases in 5-year mortality compared with patients with low levels of
      PGRN. Finally, we establish a clinically useful nomogram to predict the
      possibility of mortality for individual EC patients. In conclusion, PGRN may play
      an important role in the lymphangiogenesis through activation of VEGF-C in the EC
      patients.

PMID- 29452215
TI  - Lymphocytic colitis: pathologic predictors of response to therapy.
AB  - Although the presence of intraepithelial lymphocytosis with surface epithelial
      damage is a unifying feature of lymphocytic colitis, there are nonclassical
      features that create morphologic heterogeneity between cases. Limited data on the
      significance of these secondary histologic features are available. Cases of
      lymphocytic colitis diagnosed between 2002 and 2013 were identified using the
      Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy
      slides were reviewed and evaluated for histologic features of lymphocytic
      colitis. Clinical data including type of therapy and response to treatment were
      collected. chi2 Test (or Fisher exact test) and logistic regression analysis were
      used where appropriate. Thirty-two cases of lymphocytic colitis with complete
      clinical data and slides available for review were identified. The mean age was
      56.4 years, and the female-to-male ratio was 3:2. Eleven patients improved with
      minimal intervention (group 1), 14 patients responded to steroid therapy (group
      2), and 7 patients responded to mesalamine, bismuth subsalicylate, and/or
      cholestyramine therapy (group 3). Histologic differences in the characteristics
      of the subepithelial collagen table (P = .018), the severity of lamina propria
      inflammation (P = .042), and the presence of eosinophil clusters (P = .016) were
      seen between groups 2 and 3. Patients in group 1 were more likely to have mild
      crypt architectural distortion in their biopsies than patients in groups 2 and 3.
      Lymphocytic colitis is a heterogeneous disease, and the evaluation of histologic
      factors may help identify various subtypes and predict therapy response.

PMID- 29452216
TI  - Upregulation of Tiam1 contributes to cervical cancer disease progression and
      indicates poor survival outcome.
AB  - T lymphoma invasion and metastasis 1 (Tiam1), a guanine nucleotide exchange
      factor, is involved in the tumorigenesis of a number of malignancies. This study
      was aimed to explore the role of Tiam1 in cervical cancer progression, and
      evaluate the prognostic values. Tiam1 protein expression levels were detected by
      immunohistochemical (IHC) staining in 174 cervical cancer tissues, 92 of CINs
      (cervical intraepithelial neoplasia) and 32 of normal cervical epithelia tissues.
      Clinicopathological parameters and overall survival data were collected and
      compared between different Tiam1 statuses. The role of Tiam1 in cervical cancer
      proliferation, migration and angiogenesis were detected using si-RNA (small
      interfering RNA) transfection. In results, Tiam1 protein showed a cytoplasmic and
      nuclear staining pattern in cervical cancer tissues. The strongly positive
      expression of Tiam1 protein was observed in 51.72% (90/174) of cervical cancers,
      which was significantly higher than in CINs and normal cervical epithelia tissues
      (9.38%, 3/32). High Tiam1 protein expression was closely associated with advanced
      clinical stage, differentiation, lymph node (LN) metastasis, HPV infection and
      lower overall survival (OS) rates in cervical cancer. Multivariate analysis
      indicated that Tiam1 was an independent prognostic factor, along with clinical
      stage, in patients with cervical cancer. Additionally, Tiam1 depletion by RNAi in
      cervical cancer cells significantly decreased cell proliferation, migration and
      angiogenesis. In conclusion, our study demonstrated that upregulation of Tiam1
      contributes to cervical cancer disease progression and indicates poor survival
      outcome.

PMID- 29452217
TI  - Gene expression screening identifies CDCA5 as a potential therapeutic target in
      acral melanoma.
AB  - Acral melanoma (AM) is a rapidly progressing subtype of melanoma with poor
      prognosis. The complete array of molecular changes that occur during AM
      metastasis remains unclear. In this study, we compared the gene expression
      profiles of 6 primary and 12 lymph node metastatic AM samples by tissue
      microarray analysis. We found that the expression levels of 396 genes were
      increased and that of 766 genes were decreased in the metastatic tissues compared
      with that in the primary tumors. The top 19 genes upregulated in the metastatic
      tissue specimens were selected for high-content short interfering RNA screening.
      We found that inhibition of cell division cycle-associated 5 (CDCA5)
      significantly suppressed AM cell migration and invasion. Furthermore, we
      demonstrated that upregulation of CDCA5 was correlated with higher tumor-node
      metastases stages (P=.025) and a shorter disease-free survival in patients with
      AM (P=.038). Cox regression analyses showed that high CDCA5 expression was also
      an independent factor of disease-free survival for patients with AM (hazard ratio
      =1.86, P=.041). Overall, our data define the gene expression signature of AM
      metastasis and indicate that CDCA5 is a potential therapeutic target in AM.

PMID- 29452219
TI  - Increased CD4 counts, pain and depression are correlates of lower sleep quality
      in treated HIV positive patients with low baseline CD4 counts.
AB  - Poor sleep quality leads to increased immune activation and immune activation
      leads to worse sleep quality. South African HIV positive patients typically have
      delayed start of treatment, which has been associated with CD4+ effector T cells
      being more spontaneously activated in chronically treated patients. This cross
      sectional study investigated whether subjective sleep quality was associated with
      CD4+ T lymphocyte reconstitution in treated South African HIV+ patients. One
      hundred and thirty-nine treated HIV+ patients (109 F, age average (SD) = 43 (9))
      were recruited from Chris Hani Baragwanath Academic Hospital in Soweto,
      Johannesburg, South Africa. Participants completed questionnaires evaluating
      their subjective sleep quality (Pittsburgh Sleep Quality Index), daytime
      sleepiness (Epworth sleepiness scale), pain, and depression severity (Beck
      Depression Inventory). Univariate and multivariate analyses were run to determine
      the correlates of sleep quality in this population. Patients had been on
      antiretroviral treatment for about 4 years and had increased their CD4 counts
      from a median at baseline of 82 to 467 cells/uL. They had overall poor sleep
      quality (average (SD) PSQI = 7.7 (+/-5), 61% reporting PSQI > 5, a marker of
      lower sleep quality), 41% had clinical depression (average (SD) BDI = 17 (+/-12))
      and 55% reported pain. In two separate multivariate analyses, both the overall
      CD4 count increase from baseline (p = 0.0006) and higher current CD4 counts (p =
      0.0007) were associated with worse sleep quality, when adjusting for depression
      severity (p < 0.001), daytime sleepiness (p = 0.01) and the presence of pain (p <
      0.01). In this cohort of treated South African HIV positive patients, poor sleep
      quality was associated with higher current CD4 counts, when adjusting for
      depression severity, daytime sleepiness and pain. Further studies should
      investigate the temporal relationship between HIV-related poor sleep quality and
      underlying immune activation.

PMID- 29452218
TI  - TNFalpha disrupts blood brain barrier integrity to maintain prolonged depressive
      like behavior in mice.
AB  - Recovery from major depressive disorder is difficult, particularly in patients
      who are refractory to antidepressant treatments. To examine factors that regulate
      recovery, we developed a prolonged learned helplessness depression model in mice.
      After the induction of learned helplessness, mice were separated into groups that
      recovered or did not recover within 4 weeks. Comparisons were made between groups
      in hippocampal proteins, inflammatory cytokines, and blood brain barrier (BBB)
      permeability. Compared with mice that recovered and control mice, non-recovered
      mice displaying prolonged learned helplessness had greater hippocampal activation
      of glycogen synthase kinase-3 (GSK3), higher levels of tumor necrosis factor
      alpha (TNFalpha), interleukin-17A, and interleukin-23, increased permeability of
      the blood brain barrier (BBB), and lower levels of the BBB tight junction
      proteins occludin, ZO1, and claudin-5. Treatment with the GSK3 inhibitor TDZD-8
      reduced inflammatory cytokine levels, increased tight junction protein levels,
      and reversed impaired recovery from learned helplessness, demonstrating that
      prolonged learned helplessness is reversible and is maintained by abnormally
      active GSK3. In non-recovered mice with prolonged learned helpless, stimulation
      of sphingosine 1-phosphate receptors by Fingolimod or administration of the
      TNFalpha inhibitor etanercept repaired the BBB and reversed impaired recovery
      from prolonged learned helplessness. Thus, disrupted BBB integrity mediated in
      part by TNFalpha contributes to blocking recovery from prolonged learned
      helplessness depression-like behavior. Overall, this report describes a new model
      of prolonged depression-like behavior and demonstrates that stress-induced GSK3
      activation contributes to disruption of BBB integrity mediated by inflammation,
      particularly TNFalpha, which contributes to impaired recovery from prolonged
      learned helplessness.

PMID- 29452220
TI  - Methods for analyzing matched designs with double controls: excess risk is easily
      estimated and misinterpreted when evaluating traffic deaths.
AB  - OBJECTIVES: To demonstrate analytic approaches for matched studies where two
      controls are linked to each case and events are accumulating counts rather than
      binary outcomes. A secondary intent is to clarify the distinction between total
      risk and excess risk (unmatched vs. matched perspectives). STUDY DESIGN AND
      SETTING: We review past research testing whether elections can lead to increased
      traffic risks. The results are reinterpreted by analyzing both the total count of
      individuals in fatal crashes and the excess count of individuals in fatal
      crashes, each time accounting for the matched double controls. RESULTS: Overall,
      1,546 individuals were in fatal crashes on the 10 election days (average =
      155/d), and 2,593 individuals were in fatal crashes on the 20 control days
      (average = 130/d). Poisson regression of total counts yielded a relative risk of
      1.19 (95% confidence interval: 1.12-1.27). Poisson regression of excess counts
      yielded a relative risk of 3.22 (95% confidence interval: 2.72-3.80). The
      discrepancy between analyses of total counts and excess counts replicated with
      alternative statistical models and was visualized in graphical displays.
      CONCLUSION: Available approaches provide methods for analyzing count data in
      matched designs with double controls and help clarify the distinction between
      increases in total risk and increases in excess risk.

PMID- 29452221
TI  - A scoping review and survey provides the rationale, perceptions, and preferences
      for the integration of randomized and nonrandomized studies in evidence syntheses
      and GRADE assessments.
AB  - OBJECTIVES: To review the literature and obtain preferences and perceptions from
      experts regarding the role of randomized studies (RSs) and nonrandomized studies
      (NRSs) in systematic reviews of intervention effects. STUDY DESIGN AND SETTING:
      Scoping review and survey of experts. Using levels of certainty developed by the
      Grading of Recommendations Assessment, Development and Evaluation (GRADE) working
      group, experts expressed their preferences about the use of RS and NRS in health
      syntheses. RESULTS: Of 189 respondents, 123 had the expertise required to answer
      the questionnaire; 116 provided their extent of agreement with approaches to use
      NRS with RS. Most respondents would include NRS when RS was unfeasible (83.6%) or
      unethical (71.5%) and a majority to maximize the body of evidence (66.3%),
      compare results in NRS and RS (53.5%) and to identify subgroups (51.7%). Sizable
      minorities would include NRS and RS to address the effect of randomization
      (29.5%) or because the question being addressed was a public-health intervention
      (36.5%). In summary of findings tables, most respondents would include both
      bodies of evidence-in two rows in the same table-when RS provided moderate, low,
      or very-low certainty evidence; even when RS provided high certainty evidence, a
      sizable minority (25%) would still present results from both bodies of evidence.
      Very few (3.6%) would, under realistic circumstances, pool RS and NRS results.
      CONCLUSIONS: Most experts would include both RS and NRS in the same review under
      a wide variety of circumstances, but almost all would present results of two
      bodies of evidence separately.

PMID- 29452222
TI  - Essential medicines availability is still suboptimal in many countries: a scoping
      review.
AB  - OBJECTIVES: To identify uses of WHO Model list of essential medicines (EMs) and
      summarize studies examining EM and national EM lists (NEMLs). STUDY DESIGN AND
      SETTING: In this scoping review, we searched PubMed, Scopus, WHO website and WHO
      Regional Databases for studies on NEMLs, reimbursement medicines lists, and WHO
      EML, with no date or language restrictions. RESULTS: Three thousand one hundred
      forty-four retrieved documents were independently screened by two reviewers; 100
      full-text documents were analyzed; 37 contained data suitable for quantitative
      and qualitative analysis on EMs availability (11 documents), medicines for
      specific diseases (13 documents), and comparison of WHO EML and NEMLs (13
      documents). From the latter, two documents analyzed the relevance of evidence
      from Cochrane systematic reviews for medicines that were on NEMLs but not on the
      WHO EML. EMs availability is still suboptimal in low-income countries.
      Availability of children formulations and EMs for specific diseases such as
      chronic, cancer, pain, and reproductive health is suboptimal even in middle
      income countries. CONCLUSION: WHO EML can be used as a basic set of medicines for
      different settings. More evidence is needed into how NEMLs can contribute to
      better availability of children formulations, pain, and cancer medicines in
      developing countries.

PMID- 29452223
TI  - GRADE Guidelines: 19. Assessing the certainty of evidence in the importance of
      outcomes or values and preferences-Risk of bias and indirectness.
AB  - OBJECTIVES: The Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) working group defines patient values and preferences as the
      relative importance patients place on the main health outcomes. We provide GRADE
      guidance for assessing the risk of bias and indirectness domains for certainty of
      evidence about the relative importance of outcomes. STUDY DESIGN AND SETTING: We
      applied the GRADE domains to rate the certainty of evidence in the importance of
      outcomes to several systematic reviews, iteratively reviewed draft guidance and
      consulted GRADE members and other stakeholders for feedback. RESULTS: This is the
      first of two articles. A body of evidence addressing the importance of outcomes
      starts at "high certainty"; concerns with risk of bias, indirectness,
      inconsistency, imprecision, and publication bias lead to downgrading to moderate,
      low, or very low certainty. We propose subdomains of risk of bias as selection of
      the study population, missing data, the type of measurement instrument, and
      confounding; we have developed items for each subdomain. The population,
      intervention, comparison, and outcome elements associated with the evidence
      determine the degree of indirectness. CONCLUSION: This article provides guidance
      and examples for rating the risk of bias and indirectness for a body of evidence
      summarizing the importance of outcomes.

PMID- 29452225
TI  - Human dendritic cell immunodeficiencies.
AB  - The critical functions of dendritic cells (DCs) in immunity and tolerance have
      been demonstrated in many animal models but their non-redundant roles in humans
      are more difficult to probe. Human primary immunodeficiency (PID), resulting from
      single gene mutations, may result in DC deficiency or dysfunction. This
      relatively recent recognition illuminates the in vivo role of human DCs and the
      pathophysiology of the associated clinical syndromes. In this review, the
      development and function of DCs as established in murine models and human in
      vitro systems, discussed. This forms the basis of predicting the effects of DC
      deficiency in vivo and understanding the consequences of specific mutations on DC
      development and function. DC deficiency syndromes are associated with
      heterozygous GATA2 mutation, bi-allelic and heterozygous IRF8 mutation and
      heterozygous IKZF1 mutation. The intricate involvement of DCs in the balance
      between immunity and tolerance is leading to increased recognition of their
      involvement in a number of other immunodeficiencies and autoimmune conditions.
      Owing to the precise control of transcription factor gene expression by super
      enhancer elements, phenotypic anomalies are relatively commonly caused by
      heterozygous mutations.

PMID- 29452224
TI  - Methodological and reporting quality in laboratory studies of human eating
      behavior.
AB  - The methodological quality and reporting practices of laboratory studies of human
      eating behavior determine the validity and replicability of nutrition science.
      The aim of this research was to examine basic methodology and reporting practices
      in recent representative laboratory studies of human eating behavior. We examined
      laboratory studies of human eating behavior (N = 140 studies) published during
      2016. Basic methodology (e.g., sample size, use of participant blinding) and
      reporting practices (e.g., information on participant characteristics) were
      assessed for each study. Some information relating to participant characteristics
      (e.g., age, gender) and study methodology (e.g., length of washout periods in
      within-subjects studies) were reported in the majority of studies. However, other
      aspects of study reporting, including participant eligibility criteria and how
      sample size was determined were frequently not reported. Studies often did not
      appear to standardize pre-test meal appetite or attempt to blind participants to
      study aims. The average sample size of studies was small (between-subjects design
      studies in particular) and the primary statistical analyses in a number of
      studies (24%) were reliant on very small sample sizes that would be likely to
      produce unreliable results. There are basic methodology and reporting practices
      in the laboratory study of human eating behavior that are sub-optimal and this is
      likely to be affecting the validity and replicability of research.
      Recommendations to address these issues are discussed.

PMID- 29452226
TI  - Quantitative Proteomic Analysis Reveals Synaptic Dysfunction in the Amygdala of
      Rats Susceptible to Chronic Mild Stress.
AB  - The amygdala plays a key role in the pathophysiology of depression, but the
      molecular mechanisms underlying amygdalar hyperactivity in depression remain
      unclear. In this study, we used a chronic mild stress (CMS) protocol to separate
      susceptible and insusceptible rat subgroups. Proteomes in the amygdalae were
      analyzed differentially across subgroups based on labeling with isobaric tags for
      relative and absolute quantitation (iTRAQ) combined with mass spectrometry. Of
      2562 quantified proteins, 102 were differentially expressed. Several proteins
      that might be associated with the stress insusceptibility/susceptibility
      difference, including synapse-related proteins, were identified in the amygdala.
      Immunoblot analysis identified changes in VGluT1, NMDA GluN2A and GluN2B and AMPA
      GluA1 receptors, and PSD-95, suggesting that CMS perturbs glutamatergic
      transmission in the amygdala. Changes in these regulatory and structural proteins
      provide insight into the molecular mechanisms underlying the abnormal synaptic
      morphological and functional plasticity in the amygdalae of stress-susceptible
      rats. Interestingly, the expression level of CaMKIIbeta, potentially involved in
      regulation of glutamatergic transmission, was significantly increased in the
      susceptible group. Subsequent in vitro experimentation showed that overexpression
      of CaMKIIbeta increased the expression of PSD-95 and GluA1 in cultured
      hippocampal neurons. This result suggested that CaMKIIbeta functions upstream
      from PSD-95 and GluA1 to affect LTP-based postsynaptic functional plasticity in
      the amygdalae of susceptible rats. Therefore, amygdalar CaMKIIbeta is a potential
      antidepressant target. Collectively, our findings contribute to a better
      understanding of amygdalar synaptic plasticity in depression.

PMID- 29452228
TI  - A BACH2 Gene Variant Is Associated with Postoperative Recurrence of Crohn's
      Disease.
AB  - BACKGROUND: Crohn's disease often requires intestinal resection, which is not
      considered curative. Repeat surgical intervention is necessary in more than half
      of patients after their initial operation. Although many genetic loci are
      implicated in Crohn's disease, few have been associated with post-resection
      recurrence. STUDY DESIGN: A cohort of patients with Crohn's disease who underwent
      intestinal resection was analyzed to determine genetic and clinical factors
      associated with post-resection recurrence. Genotype was assessed at 8 loci
      associated with adaptive immunity (SMAD3, IL10RB, IL15RA, BACH2, IL12B, IL18RAP,
      IFNGR2, and JAK2). Univariate and multivariable survival analyses were performed
      using a log-rank test and Cox-proportional hazard model, respectively. RESULTS:
      One hundred and ninety-one patients with Crohn's disease and 11.2 years mean
      postoperative follow-up were included. Forty-six percent experienced a surgical
      recurrence. Factors associated with increased incidence of recurrence included
      male sex (p = 0.05) and shortened time to first intestinal operation (5.0 vs 7.3
      years; p = 0.03); inflammatory disease behavior was associated with a lower
      chance of repeat operation (p < 0.01). Of the loci assessed on multivariable
      analysis, homozygosity for a risk allele at BACH2 (rs1847472) was significantly
      associated with disease recurrence (hazard ratio 1.54; 95% CI 1.00 to 2.36; p <
      0.05). CONCLUSIONS: We identify BACH2 as a susceptibility locus for postoperative
      recurrence of Crohn's disease in our cohort. BACH2 is critical in the
      differentiation and function of T cells, as a regulator of B-cell activity, and
      is associated with several dysregulated immunologic phenomena. Its identification
      as a risk locus in postoperative Crohn's disease recurrence suggests a potential
      role for regulatory T cells, effector T cells, humoral immunity, and immunologic
      memory in the development of this disease process.

PMID- 29452227
TI  - Age and experience dependent changes in Egr-1 expression during the ontogeny of
      the context preexposure facilitation effect (CPFE).
AB  - The context preexposure facilitation effect (CPFE) is a variant of contextual
      fear conditioning in which acquisition of the contextual representation and
      association of the retrieved contextual memory with an immediate foot-shock are
      separated by 24 h. During the CPFE, learning- related expression patterns of the
      early growth response-1 gene (Egr-1) vary based on training phase and brain sub
      region in adult and adolescent rats (Asok, Schreiber, Jablonski, Rosen, &
      Stanton, 2013; Schreiber, Asok, Jablonski, Rosen, & Stanton, 2014; Chakraborty,
      Asok, Stanton, & Rosen, 2016). The current experiments extended our previous
      findings by examining Egr-1 expression in infant (PD17) and juvenile (PD24) rats
      during the CPFE using preexposure protocols involving single-exposure (SE) or
      multiple-exposure (ME) to context. Following a 5 min preexposure to the training
      context (i.e. the SE protocol), Egr-1 expression in the medial prefrontal cortex
      (mPFC), dorsal hippocampus (dHPC) and lateral nucleus of the amygdala (LA) was
      differentially increased in PD24 rats relative to PD17 rats. In contrast,
      increased Egr-1 expression following an immediate foot-shock (2s, 1.5 mA) did not
      differ between PD17 and PD24 rats, and was not learning-related. Interestingly,
      increasing the number of exposures to the training chamber on the preexposure day
      (i.e. ME protocol) altered training-day expression such that a learning-related
      increase in expression was observed in the mPFC in PD24 but not PD17 rats.
      Together, these results illustrate a clear maturation of Egr-1 expression that is
      both age- and experience-dependent. In addition, the data suggest that regional
      activity and plasticity within the mPFC on the preexposure but not the training
      day may contribute to the ontogenetic profile of the effect. Further studies are
      necessary to elucidate the causal role of sub-region-specific neuroplasticity in
      the ontogeny of the CPFE.

PMID- 29452229
TI  - Strategic Partnerships in Surgery: A Model for the US.

PMID- 29452230
TI  - A regulatory circuitry between miR-193a/miR-600 and WT1 enhances leukemogenesis
      in acute myeloid leukemia.
AB  - The aberrant overexpression of Wilms tumor-1 (WT1) in acute myeloid leukemia
      (AML) plays an important role in blast cell survival by enhancing proliferation
      and inhibiting apoptosis. However, the mechanism underlying the overexpression of
      WT1 remains unclear. Here, we identified miR-193a (miR-193a-5p) and miR-600
      targeting and degrading WT1. MiR-193a and miR-600 synergistically reduced WT1
      expression and suppressed the activity of a luciferase reporter by binding coding
      sequence and the 3'-untranslated region of WT1 mRNA, respectively. Furthermore,
      the expression of miR-193a and miR-600 was decreased in AML patients compared
      with normal controls. DNA hypermethylation in pre-miR-193a promoter, but not pre
      miR-600 promoter, caused the downregulation of miR-193a. Most intriguingly,
      ectopic expression of WT1 inhibited miR-600 expression, in turn, by binding the
      putative pre-miR-600 promoter, leading to the downregulation of miR-600 in AML
      blasts. Ectopic expression of miR-193a and miR-600 synergistically inhibited cell
      proliferation, induced apoptosis, and decreased colony formation in leukemia
      cells. Finally, overexpression of miR-193a and miR-600 decreased the growth of
      K562-inoculated tumor xenografts and extended survival time in THP1-transplanted
      leukemia mice. In conclusion, these data reveal an important role of miRNAs-WT1
      circuitry in leukemia cells and the therapeutic promise of restoring miR-193a and
      miR-600 expression in AML patients.

PMID- 29452231
TI  - The association of 22 Y chromosome short tandem repeat loci with initiative
      aggressive behavior.
AB  - Aggressive behavior represents an important public concern and a clinical
      challenge to behaviorists and psychiatrists. Aggression in humans is known to
      have an important genetic basis, so to investigate the association of Y
      chromosome short tandem repeat (Y-STR) loci with initiative-aggressive behavior,
      we compared allelic and haplotypic distributions of 22 Y-STRs in a group of
      Chinese males convicted of premeditated extremely violent crimes (n = 271) with a
      normal control group (n = 492). Allelic distributions of DYS533 and DYS437 loci
      differed significantly between the two groups (P < 0.05). The case group had
      higher frequencies of DYS533 allele 14, DYS437 allele 14, and haplotypes 11-14 of
      DYS533-DYS437 compared with the control group. Additionally, the DYS437 allele 15
      frequency was significantly lower in cases than controls. No frequency
      differences were observed in the other 20 Y-STR loci between these two groups.
      Our results indicate a genetic role for Y-STR loci in the development of
      initiative aggression in non-psychiatric subjects.

PMID- 29452232
TI  - Long noncoding RNA PVT1 promotes EMT via mediating microRNA-186 targeting of
      Twist1 in prostate cancer.
AB  - The pathogenesis and the underlying mechanism of endothelial-mesenchymal
      transition in prostate cancer remain unclear. Plasmacytoma variant translocation
      1 (PVT1), a novel long non-coding RNA maps to 8q24.21, and in many tumor studies
      the up-regulation of PVT1 has already been reported. PVT1 is closely related to
      tumor cell proliferation, invasion, and metastasis. In this study, we employed a
      combination of techniques to study the role of PVT1 in prostate cancer, which
      included bioinformatic analysis, Western blotting and cell migration assays of
      prostate cancer cell lines. We report that PVT1 promotes prostate cancer invasion
      and metastasis by modulating EMT. Furthermore, PVT1 can promote EMT by up
      regulation of Twist1, a transcription factor associated with EMT. We then
      confirmed that PVT1 acts as a sponge for miRNA-186-5p and positively regulates
      Twist1 by a sponge effect. Therefore, this study has revealed a novel MECHANISM
      for the promotion of EMT in prostate cancer by PVT1. Our findings suggest that
      the PVT1/miR-186/Twist1 regulatory axis may be a new therapeutic target for
      prostate cancer.

PMID- 29452233
TI  - Role of adipose tissue derived stem cells differentiated into insulin producing
      cells in the treatment of type I diabetes mellitus.
AB  - Generation of new beta cells is an important approach in the treatment of type 1
      diabetes mellitus (type 1 DM). Adipose tissue-derived stem cells (ADSCs) might be
      one of the best sources for cell replacement therapy for diabetes. Therefore,
      this work aimed to test the possible role of transplanted insulin-producing cells
      (IPCs) differentiated from ADSCs in treatment of streptozotocin (STZ) induced
      type I DM in rats. Type 1 DM was induced by single intra peritoneal injection
      with STZ (50 mg/kg BW). Half of the diabetic rats were left without treatment and
      the other half were injected with differentiated IPCs directly into the pancreas.
      ADSCs were harvested, cultured and identified by testing their phenotypes through
      flow cytometry. They were further subjected to differentiation into IPCs using
      differentiation medium. mRNA expression of pancreatic transcription factors
      (pdx1), insulin and glucose transporter-2 genes by real time PCR was done to
      detect the cellular differentiation and confirmed by stimulated insulin
      secretion. The pancreatic tissues from all groups were examined 2 months after
      IPC transplantation and were subjected to histological, Immunohistochemical and
      morphometric study. The differentiated IPCs showed significant expression of
      pancreatic beta cell markers and insulin secretion in glucose dependent manner.
      Treatment with IPCs induced apparent regeneration, diffused proliferated islet
      cells and significant increase in C-peptide immune reaction. We concluded that
      transplantation of differentiated IPCs improved function and morphology of Islet
      cells in diabetic rats. Consequently, this therapy option may be a promising
      therapeutic approach to patient with type 1 DM if proven to be effective and
      safe.

PMID- 29452234
TI  - Exploring the deleterious SNPs in XRCC4 gene using computational approach and
      studying their association with breast cancer in the population of West India.
AB  - Non-homologous end joining (NHEJ) pathway has pivotal role in repair of double
      strand DNA breaks that may lead to carcinogenesis. XRCC4 is one of the essential
      proteins of this pathway and single-nucleotide polymorphisms (SNPs) of this gene
      are reported to be associated with cancer risks. In our study, we first used
      computational approaches to predict the damaging variants of XRCC4 gene. Tools
      predicted rs79561451 (S110P) nsSNP as the most deleterious SNP. Along with this
      SNP, we analysed other two SNPs (rs3734091 and rs6869366) to study their
      association with breast cancer in population of West India. Variant rs3734091 was
      found to be significantly associated with breast cancer while rs6869366 variant
      did not show any association. These SNPs may influence the susceptibility of
      individuals to breast cancer in this population.

PMID- 29452235
TI  - Improved strength of silk fibers in Bombyx mori trimolters induced by an anti
      juvenile hormone compound.
AB  - BACKGROUND: Bombyx mori silk fibers with thin diameters have advantages of
      lightness and crease-resistance. Many studies have used anti-juvenile hormones to
      induce trimolters in order to generate thin silk; however, there has been
      comparatively little analysis of the morphology, structure and mechanical
      properties of trimolter silk. METHODS: This study induced two kinds of trimolters
      by appling topically anti-juvenile hormones and obtained thin diameter silk.
      Scanning electron microscope (SEM), FTIR analysis, tensile mechanical testing,
      chitin staining were used to reveal that the morphology, conformation and
      mechanical property of the trimolter silk. RESULTS: Cocoon of trimolters were
      highly densely packed by thinner fibers and thus had small apertures. We found
      that the conformation of trimolter silk fibroin changed and formed more beta
      sheet structures. In addition, analysis of mechanical parameters yielded a higher
      Young's modulus and strength in trimolter silk than in the control. By chitin
      staining of silk gland, we postulated that the mechanical properties of
      trimolters' silk was enhanced greatly during to the structural changes of silk
      gland. CONCLUSION: We induced trimolters by anti-juvenile hormones and the
      resulting cocoons were more closely packed and had smaller silk fiber diameters.
      We found that the conformation of trimolters silk fibroin had a higher content of
      beta-sheet structures and better mechanical properties. GENERAL SIGNIFICANCE: Our
      study revealed the structures and mechanical properties of trimolter silk, and
      provided a valuable reference to improve silk quality by influencing molting in
      silkworms.

PMID- 29452236
TI  - Cardiac and placental mitochondrial characterization in a rabbit model of
      intrauterine growth restriction.
AB  - BACKGROUND: Intrauterine growth restriction (IUGR) is associated with
      cardiovascular remodeling persisting into adulthood. Mitochondrial bioenergetics,
      essential for embryonic development and cardiovascular function, are regulated by
      nuclear effectors as sirtuins. A rabbit model of IUGR and cardiovascular
      remodeling was generated, in which heart mitochondrial alterations were observed
      by microscopic and transcriptomic analysis. We aimed to evaluate if such
      alterations are translated at a functional mitochondrial level to establish the
      etiopathology and potential therapeutic targets for this obstetric complication.
      METHODS: Hearts and placentas from 16 IUGR-offspring and 14 controls were
      included to characterize mitochondrial function. RESULTS: Enzymatic activities of
      complexes II, IV and II + III in IUGR-hearts (-11.96 +/- 3.16%; -15.58 +/- 5.32%;
      -14.73 +/- 4.37%; p < 0.05) and II and II + III in IUGR-placentas (-17.22 +/-
      3.46%; p < 0.005 and -29.64 +/- 4.43%; p < 0.001) significantly decreased. This
      was accompanied by a not significant reduction in CI-stimulated oxygen
      consumption and significantly decreased complex II SDHB subunit expression in
      placenta (-44.12 +/- 5.88%; p < 0.001). Levels of mitochondrial content, Coenzyme
      Q and cellular ATP were conserved. Lipid peroxidation significantly decreased in
      IUGR-hearts (-39.02 +/- 4.35%; p < 0.001), but not significantly increased in
      IUGR-placentas. Sirtuin3 protein expression significantly increased in IUGR
      hearts (84.21 +/- 31.58%; p < 0.05) despite conserved anti-oxidant SOD2 protein
      expression and activity in both tissues. CONCLUSIONS: IUGR is associated with
      cardiac and placental mitochondrial CII dysfunction. Up-regulated expression of
      Sirtuin3 may explain attenuation of cardiac oxidative damage and preserved ATP
      levels under CII deficiency. GENERAL SIGNIFICANCE: These findings may allow the
      design of dietary interventions to modulate Sirtuin3 expression and consequent
      regulation of mitochondrial imbalance associated with IUGR and derived
      cardiovascular remodeling.

PMID- 29452237
TI  - A redox-sensitive signaling pathway mediates pro-angiogenic effect of chlordecone
      via estrogen receptor activation.
AB  - AIM: Chlordecone is able to induce pro-angiogenic effect through an estrogen
      receptor (ERalpha) pathway involving NO release and VEGF. The present study aimed
      to determine the molecular mechanisms by which chlordecone promotes angiogenesis
      in human endothelial cells. RESULTS: High but not low concentration of
      chlordecone increased mitochondrial respiratory capacity and mitochondrial DNA
      content in endothelial cells. The ROS scavenger MnTMPyP was able to prevent the
      increase of both VEGF expression and capillary length induced by chlordecone. A
      significant increase of cytoplasmic O2- production was observed after 1 and 4 h
      incubation of chlordecone, but not after 2 h. The NADPH oxidase inhibitor
      apocynin or silencing p47phox prevented angiogenesis and tube formation but also
      the increase in production of O2- at 1 h. In addition, apocynin as well silencing
      p47phox prevented eNOS activation and the NO synthase inhibitor L-NAME inhibited
      mitochondrial O2-production. All the previous effects of chlordecone were
      prevented by fulvestrant. CONCLUSION: Our results indicate that an adaptation of
      the mitochondrial energy metabolism occurs in the chlordecone angiogenic
      response. Finally, we showed that chlordecone induces endothelial cells
      angiogenesis by a cross-talk involving NADPH oxidase and mitochondrial O2-via a
      NO sensitive pathways through activation of ERalpha. These findings propose that
      a molecular mechanism may partly explain the epidemiological evidence implicating
      chlordecone as risk factor carcinogenesis.

PMID- 29452239
TI  - Letter to the editor.

PMID- 29452238
TI  - Human adipose tissue-derived stromal cells in combination with exogenous stimuli
      facilitate three-dimensional network formation of human endothelial cells derived
      from various sources.
AB  - In natural tissues, the nutrition of cells and removal of waste products is
      facilitated by a dense capillary network which is generated during development.
      This perfusion system is also indispensable for tissue formation in vitro.
      Nutrition depending solely on diffusion is not sufficient to generate tissues of
      clinically relevant dimensions, which is a core aim in tissue engineering
      research. In this study, the establishment of a vascular network was investigated
      in a self-assembling approach employing endothelial and mural cells. The process
      of vascularization was analyzed in constructs based on a carrier matrix of
      decellularized porcine small intestinal submucosa (SIS). A three-dimensional
      hydrogel containing MatrigelTM, collagen, and respective cells was casted on top
      of the SIS. Various types of human endothelial cells (hECs), e.g. HUVECs, cardiac
      tissue ECs (hCECs), pulmonary artery ECs (hPAECs), and iPSC-derived ECs, were co
      cultured with human adipose tissue-derived stromal cells (hASCs) within the
      hydrogel. Analyzed hECs were able to self-assemble and form three-dimensional
      networks harboring small caliber lumens within the hydrogel constructs in the
      presence of hASCs as supporting cells. Additionally, microvessel assembling
      required exogenous growth factor supplementation. This study demonstrates the
      development of stable vascularized hydrogels applying hASCs as mural cells in
      combination with various types of hECs, paving the way for the generation of
      clinically applicable tissue engineered constructs.

PMID- 29452240
TI  - The effect of non-TNF-targeted biologics and small molecules on insulin
      resistance in inflammatory arthritis.
AB  - Inflammatory arthritides are chronic diseases characterised by an increase in
      cardiovascular risk, largely attributable to the synergy between high-grade
      systemic inflammation and an elevated prevalence of traditional cardiovascular
      risk factors. Amongst the latter, insulin resistance and type 2 diabetes (T2D)
      play a key position. Previous studies demonstrated a potential insulin
      sensitizing effect of anti-TNF biologic medications. For converse, less is known
      about the role of newer biologics or small molecules. For this reason, we
      performed a systematic review of the literature in order to identify the
      available data on the effect on insulin resistance of non-TNF targeting biologics
      and small molecules approved for the treatment of inflammatory arthritides. The
      search strategy initially retrieved 486 records of which only 10 articles were
      selected for inclusion in the final review. According to the available evidence,
      some of the newest molecules, in particular tocilizumab and abatacept, may have a
      role in improving insulin sensitivity; for converse, anakinra-mediated effect on
      glucose metabolism may exploit different facets of T2D pathophysiology, such as
      the preservation of beta-cell function. However, the data available on this issue
      are largely inconsistent and future, adequately designed studies are still needed
      to clarify the differential impact of novel therapeutics on individual
      pathophysiological features of T2D and other emerging cardiovascular risk
      factors.

PMID- 29452241
TI  - Raw material variability of an active pharmaceutical ingredient and its relevance
      for processability in secondary continuous pharmaceutical manufacturing.
AB  - Active Pharmaceutical Ingredients (API) raw material variability is not always
      thoroughly considered during pharmaceutical process development, mainly due to
      low quantities of drug substance available. However, synthesis, crystallization
      routes and production sites evolve during product development and product life
      cycle leading to changes in physical material attributes which can potentially
      affect their processability. Recent literature highlights the need for a global
      approach to understand the link between material synthesis, material variability,
      process and product quality. The study described in this article aims at
      explaining the raw material variability of an API using extensive material
      characterization on a restricted number of representative batches using
      multivariate data analysis. It is part of a larger investigation trying to link
      the API drug substance manufacturing process, the resulting physical API raw
      material attributes and the drug product continuous manufacturing process. Eight
      API batches produced using different synthetic routes, crystallization, drying,
      delumping processes and processing equipment were characterized, extensively.
      Seventeen properties from seven characterization techniques were retained for
      further analysis using Principal Component Analysis (PCA). Three principal
      components (PCs) were sufficient to explain 92.9% of the API raw material
      variability. The first PC was related to crystal length, agglomerate size and
      fraction, flowability and electrostatic charging. The second PC was driven by the
      span of the particle size distribution and the agglomerates strength. The third
      PC was related to surface energy. Additionally, the PCA allowed to summarize the
      API batch-to-batch variability in only three PCs which can be used in future drug
      product development studies to quantitatively evaluate the impact of the API raw
      material variability upon the drug product process. The approach described in
      this article could be applied to any other compound which is prone to batch-to
      batch variability.

PMID- 29452242
TI  - Monolithic zirconia crowns in the aesthetic zone in heavy grinders with severe
      tooth wear - An observational case-series.
AB  - OBJECTIVES: The aim of this study was to assess the clinical outcomes and patient
      satisfaction with monolithic zirconia crowns in patients with severe tooth wear
      (>=1/3 of the tooth crown) in the aesthetic zone. METHODS: The historical
      prospective study sample consisted of 13 patients previously treated with a total
      of 84 monolithic zirconia crowns. The patients had been treated in a private
      clinic in Bergen, Norway, in the period 2012 to 2014. All patients were men, aged
      35-67 years (mean age 56.3 years) and had been in need of prosthetic
      rehabilitation because of severe tooth wear in the aesthetic zone. Technical
      complications as well as biologic findings were registered when the crowns had
      been in function one to three years (mean 20 months). The patients completed a
      self-administered questionnaire regarding satisfaction with aesthetic and
      function. RESULTS: No biological complications were registered in 79 of the
      crowns (94%), and technical complications were registered in only two patients.
      All patients were satisfied with the aesthetic and function of the monolithic
      zirconia crowns and would choose the same treatment modality if they were to be
      treated again. CONCLUSIONS: Within the limitations of this study, we conclude
      that the rate of clinical complications was low and that the patients were
      satisfied with the aesthetic as well as the function of the monolithic zirconia
      crowns. CLINICAL SIGNIFICANCE: Monolithic zirconia crowns may provide a valid
      treatment modality in the aesthetic zone in patients with severe tooth wear.

PMID- 29452243
TI  - Evaluation of ozonated water using ASTM E1174 for standardized testing of
      handwash formulations for healthcare personnel.
AB  - Removal of bacteria by handwashing with ozonated water was evaluated using the
      ASTM E1174 standard test method. Thirty healthy volunteers were assigned randomly
      to three groups: ozonated water, antimicrobial soap and water, and non
      antimicrobial soap and water. A 3 log10 cfu reduction was achieved by washing
      hands with ozonated water or antimicrobial soap and water. However, ozonated
      water was not significantly superior to non-antimicrobial soap and water.
      Ozonated water may remove bacteria from the hands to at least a similar extent as
      that by non-antimicrobial soap and water in the absence of visible dirt or body
      fluid contamination.

PMID- 29452244
TI  - Does saline enema during the first stage of labour reduce the incidence of
      Clostridium difficile colonization in neonates? A randomized controlled trial.
AB  - BACKGROUND: Maternal rectal enemas may reduce neonatal bacterial exposure during
      labour, which may reduce the risk of neonatal colonization with Clostridium
      difficile. The aim of this study was to determine the effectiveness of a saline
      enema during the first stage of labour in reducing neonatal colonization with C.
      difficile. METHODS: This study was conducted at Cairo University Hospital, Egypt
      from January 2016 to July 2016. Asymptomatic mothers with uncomplicated vaginal
      delivery and their neonates without diarrhoea were included. The study group
      underwent saline enema, and the control group had no intervention. Stool samples
      were collected from neonates one week after delivery. The primary outcome was the
      detection of C. difficile in stool culture and direct detection of C. difficile
      Toxin A and Toxin B by enzyme-linked immunosorbent assay. FINDINGS: The two
      groups were comparable (P>0.05) in terms of age, gravidity, parity, body mass
      index and gestational age. C. difficile was detected in 13.54% and 37.63% of
      stool cultures from the enema group and the control group, respectively
      (P<0.001). Direct detection of Toxins A and B was positive in 22.92% of cases in
      the enema group and 53.76% of cases in the control group (P<0.001). CONCLUSION:
      This study suggests that a saline enema for the mother during the first stage of
      labour may be useful in reducing the risk of neonatal gut colonization by C.
      difficile.

PMID- 29452245
TI  - Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide
      Using Non-First-Degree Related Donors.
AB  - Outcomes of nonmyeloablative (NMA) haploidentical (haplo) blood or marrow
      transplant (BMT) with post-transplantation cyclophosphamide (PTCy) using non
      first-degree relatives are unknown. We evaluated 33 consecutive adult patients
      (median age, 56 years) with hematologic malignancies who underwent NMA haplo T
      cell-replete BMT with PTCy at Johns Hopkins using second- or third-degree related
      donors. Donors consisted of 10 nieces (30%), 9 nephews (27%), 7 first cousins
      (21%), 5 grandchildren (15%), and 2 uncles (6%). Thirty-one patients (94%)
      reached full donor chimerism by day 60. The estimated cumulative incidence (CuI)
      of grades II to IV acute graft-versus-host disease (aGVHD) at day 180 was 24%
      (90% confidence interval [CI], 9% to 38%). Only 1 patient experienced grades III
      to IV aGVHD. At 1 year the CuI of chronic GVHD was 10% (90% CI, 0% to 21%). The
      CuI of nonrelapse mortality at 1 year was 5% (90% CI, 0% to 14%). At 1 year the
      probability of relapse was 31% (90% CI, 12% to 49%), progression-free survival
      64% (90% CI, 48% to 86%), and overall survival 95% (90% CI, 87% to 100%). The 1
      year probability of GVHD-free, relapse-free survival was 57% (90% CI, 41% to
      79%). NMA haplo BMT with PTCy from non-first-degree relatives is an acceptably
      safe and effective alternative donor platform, with results similar to those seen
      with first-degree relatives.

PMID- 29452246
TI  - BMP signaling-driven osteogenesis is critically dependent on Prdx-1 expression
      mediated maintenance of chondrocyte prehypetrophy.
AB  - During endochondral ossification, cartilage template is eventually replaced by
      bone. This process involves several well characterized, stereotypic, molecular
      and cellular changes in the cartilage primordia. These steps involve transition
      from resting to proliferative and then pre-hypertrophic to finally hypertrophic
      cartilage. BMP signaling is necessary and sufficient for osteogenesis. However,
      the specific step(s) of endochondral ossification in which BMP signaling plays an
      essential role is not yet known. In this study we have identified Prdx1, a known
      scavenger of ROS, to be expressed in pre-hypertrophic chondrocytes in a BMP
      signaling-dependent manner. We demonstrate that BMP signaling inhibition
      increases ROS levels in osteogenic cells. Further, Prdx1 regulates osteogenesis
      in vivo by helping maintenance of Ihh expressing pre-hypertrophic cells, in turn
      regulating these cells' transition into hypertrophy. Therefore, our data suggests
      that one of the key roles of BMP signaling in endochondral ossification is to
      maintain pre-hypertrophic state.

PMID- 29452247
TI  - Persistent candidemia despite appropriate fungal therapy: First case of Candida
      auris from the United Arab Emirates.
AB  - In this case, we report an elderly patient with multiple chronic conditions and
      prolonged intensive care unit (ICU) stays who had recurrent Candida auris (C.
      auris) in blood despite antifungal therapy. C. auris was misidentified using
      conventional automated identification system as Candida haemulonii resulting in
      delayed diagnosis. The isolate showed increasing minimum inhibitory
      concentrations (MICs) to different antifungal drugs and persisted in the
      patient's blood before the patient deceased. This is the first case of C. auris
      reported from the United Arab Emirates (UAE); laboratories should be aware of
      this Candida species and should confirm suspected cases since it is an emerging
      multi-drug resistant and health-care associated Candida.

PMID- 29452248
TI  - Mercaptopyruvate acts as endogenous vasodilator independently of 3
      mercaptopyruvate sulfurtransferase activity.
AB  - Hydrogen sulfide (H2S) is produced by the action of cystathionine-beta-synthase
      (CBS), cystathionine-gamma-lyase (CSE) or 3-mercaptopyruvate sulfurtransferase (3
      MST). 3-MST converts 3-mercaptopyruvate (MPT) to H2S and pyruvate. H2S is
      recognized as an endogenous gaseous mediator with multiple regulatory roles in
      mammalian cells and organisms. In the present study we demonstrate that MPT, the
      endogenous substrate of 3-MST, acts also as endogenous H2S donor. Colorimetric,
      amperometric and fluorescence based assays demonstrated that MPT releases H2S in
      vitro in an enzyme-independent manner. A functional study was performed on aortic
      rings harvested from C57BL/6 (WT) or 3-MST-knockout (3-MST-/-) mice with and
      without endothelium. MPT relaxed mouse aortic rings in endothelium-independent
      manner and at the same extent in both WT and 3-MST-/- mice. N5-(1-Iminoethyl)-l
      ornithine dihydrochloride (L-NIO, an inhibitor of endothelial nitric oxide
      synthase) as well as 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ, a soluble
      guanylyl cyclase inhibitor) did not affect MPT relaxant action. Conversely,
      hemoglobin (as H2S scavenger), as well as glybenclamide (an ATP-dependent
      potassium channel blocker) markedly reduced MPT-induced relaxation. The
      functional data clearly confirmed a non enzymatic vascular effect of MPT. In
      conclusion, MPT acts also as an endogenous H2S donor and not only as 3-MST
      substrate. MPT could, thus, be further investigated as a means to increase H2S in
      conditions where H2S bioavailability is reduced such as hypertension, coronary
      artery disease, diabetes or urogenital tract disease.

PMID- 29452249
TI  - Expression and therapeutic implications of cyclin-dependent kinase 4 (CDK4) in
      osteosarcoma.
AB  - Overexpression and/or hyperactivation of cyclin-dependent kinase 4 (CDK4) has
      been found in many types of human cancers, and a CDK4 specific inhibitor,
      palbociclib, has been recently approved by the FDA for the treatment of breast
      cancer. However, the expression and the therapeutic potential of CDK4 in
      osteosarcoma remain unclear. In the present study, CDK4 was found to be highly
      expressed in human osteosarcoma tissues and cell lines as compared with normal
      human osteoblasts. Elevated CDK4 expression correlated with metastasis potential
      and poor prognosis in osteosarcoma patients as determined by immunohistochemical
      analysis in a human osteosarcoma tissue microarray (TMA). CDK4 inhibition by
      either palbociclib or specific small interference RNA (siRNA) exhibited dose
      dependent inhibition of osteosarcoma cell proliferation and growth, accompanied
      by suppression of the CDK4/6-cyclinD-Rb signaling pathway. Flow cytometry
      analysis showed that CDK4 knockdown arrested osteosarcoma cells in the G1 phase
      of the cell cycle and induced cell apoptosis. Furthermore, inhibition of CDK4
      significantly decreased osteosarcoma cell migration in vitro determined by the
      wound healing assay. These data highlight that CDK4 may be a potential promising
      therapeutic target in the treatment of human osteosarcoma.

PMID- 29452250
TI  - Hepcidin protects grass carp (Ctenopharyngodon idellus) against Flavobacterium
      columnare infection via regulating iron distribution and immune gene expression.
AB  - Columnaris disease (CD) caused by Flavobacterium columnare (F. columnare) is lack
      of knowledge on effective treatment measures. Bacterial pathogens require iron as
      an essential nutrient to infect the host. While hepcidin acts as a master
      regulator in iron metabolism, its contribution to host defense is emerging as
      complex and multifaceted. In vitro, recombinant Ctenopharyngodon idellus (C.
      idellus) hepcidin (CiHep) and synthetic CiHep both showed the ability to increase
      the expression of hepcidin and ferritin in C. idellus kidney cells, especially
      the recombinant CiHep. In vivo, recombinant CiHep improved the survival rate of
      C. idellus challenged with F. columnare. In addition, the fish fed diet
      containing recombinant CiHep (group H-1) had a higher survival rate than other
      pretreatment groups. The study showed that recombinant CiHep regulated iron
      metabolism causing iron redistribution, decreasing serum iron levels and
      increasing iron accumulation in the hepatopancreas. Moreover, the expression of
      iron-related genes was upregulated in various degrees at a different time except
      for group H-1. Immune-related genes were also evaluated, showing higher
      expression in the groups pretreated with CiHep at an early stage of infection. Of
      note, a clear upregulation of more immune genes occurred in the groups pretreated
      with recombinant CiHep than that pretreated with synthetic CiHep in the late
      stage of infection. In conclusion, the recombinant CiHep has a protective effect
      on the host response to bacterial pathogens. We speculate that hepcidin protects
      C. idellus against F. columnare infection via regulating the iron distribution
      and immune gene expression.

PMID- 29452252
TI  - Compared to what? The placebo effect in dry eye therapy.

PMID- 29452251
TI  - Using in vitro derived enzymatic reaction rates of metabolism to inform pesticide
      body burdens in amphibians.
AB  - Understanding how pesticide exposure to non-target species influences toxicity is
      necessary to accurately assess the ecological risks these compounds pose. To
      assess the potential metabolic activation of broad use pesticides in amphibians,
      in vitro and in vivo metabolic rate constants were derived from toad (Anaxyrus
      terrestris) livers in experiments measuring the depletion of atrazine (ATZ),
      triadimefon (TDN), and fipronil (FIP) as well as formation of their metabolites.
      To determine the predictability of these in vitro derived rate constants,
      Fowler's toads (Anaxyrus fowleri) were exposed to soil contaminated with each of
      the pesticides at maximum application rate. Desethyl atrazine (DEA) and
      deisopropyl atrazine (DIA), both metabolites of ATZ, exhibited similar velocities
      (Vmax) while the KM constant for DIA was two times higher than DEA. TDN was
      metabolized into two diastereomers of triadimenol (TDL A and TDL B), where TDL B
      had a Vmax around two times higher than TDL A. The metabolite fipronil sulfone's
      Vmax and KM were 150 pmol min-1 mg-1 and 29 MUM, respectively. While intrinsic
      clearance rates for the pesticides ranged from 0.54 to 38.31 mL min-1 kg-1. Thus,
      gaining knowledge on differences in metabolism of pesticides within amphibians is
      important in estimating risk to these non-target species since the inherent
      toxicity of metabolites can differ from the parent compound.

PMID- 29452253
TI  - Remote limb ischemic postconditioning protects against cerebral ischemia
      reperfusion injury by activating AMPK-dependent autophagy.
AB  - Remote limb ischemic postconditioning (RIPoC) is a promising adjunct treatment
      for cerebral ischemia-reperfusion (IR) injury. However, the underlying mechanisms
      have not been fully elucidated yet. The present study aims to investigate
      potential involvement and regulatory mechanisms of autophagy in RIPoC treatment
      against cerebral IR injury in mice. Mice were subjected to 2 h middle cerebral
      artery occlusion (MCAO) then treated with vehicle, 3-methyladenine (3-MA, an
      autophagy inhibitor), or compound C (an AMPK inhibitor) at the onset of
      reperfusion. RIPoC was carried out by 3 cycles of 10-min occlusion-reperfusion of
      bilateral femoral artery at the beginning of the reperfusion. Infarct volume,
      neurological score, and brain water content of the mice were assessed after 12 h
      reperfusion. Autophagy markers, cell apoptosis markers, and AMPK pathway activity
      were also evaluated. Our results indicated that RIPoC treatment reduced
      neurological deficits, brain water content, and infarct volume after IR.
      Meanwhile, RIPoC was proved to induce autophagy and activate AMPK pathway.
      Furthermore, the RIPoC-induced autophagy and neuroprotection were abolished by 3
      MA and partially blocked by compound C. In conclusion, the present study suggests
      that RIPoC attenuates cerebral IR injury by activating AMPK-dependent autophagy.

PMID- 29452254
TI  - Response to the question (Ref> No.: JN2017754).

PMID- 29452255
TI  - Radiofrequency ablation of premature ventricular contractions originating from
      uncommon sites of right ventricle.
AB  - Premature Ventricular Contraction (PVC)/ventricular tachycardia (VT) with left
      bundle branch block (LBBB) morphology and inferior axis has been described
      classically to originate from the right ventricular outflow tract (RVOT). Some
      uncommon sites of idiopathic ventricular arrhythmia (VA) origins have been
      revealed including tricuspid annulus (TA) and right ventricular (RV) inflow free
      wall region. We present a series of two cases who have undergone
      electrophysiological study and successful radiofrequency ablation of frequent
      monomorphic PVCs with LBBB pattern originating from relatively uncommon sites of
      RV - TA and RV inflow free wall region.

PMID- 29452256
TI  - Modulation of oxidative stress response by flaxseed oil: Role of lipid
      peroxidation and underlying mechanisms.
AB  - Polyunsaturated fatty acids (PUFA's) are majorly classified as omega-3 and omega
      6 fatty acids. The eicosapentaenoic acid (EPA, omega-3:20-5), docosahexaenoic
      acid (DHA, omega-3:22-6) and alpha-linolenic acid (ALA, omega-3:18-3) are known
      omega-3 fatty acids, extracted from animal (e.g fish oil) and plant sources (e.g
      flaxseed oil). Furthermore, linoleic acid (LA, omega-6:18-2) is recognized as
      omega-6 fatty acid and the most prominent biological fatty acid with a pro
      inflammatory response. Flaxseed oil has variety of biological roles, due to the
      significant amount of omega-3/omega-6 fatty acids. Numerous studies have reported
      that ALA (omega-3:18-3) and LA (omega-6:18-2) has diverse pharmacological
      activities. The ALA (omega-3:18-3) and LA (omega-6:18-2) are recognised to be the
      pharmacological antagonist. For example, ALA (omega-3:18-3) is recognised as anti
      inflammatory, whereas LA (omega-6:18-2) is considered to be pro-inflammatory.
      PUFA's get oxidized in three ways; firstly, free radical-mediated pathway,
      secondly non-free radical non-enzymatic metabolism, and lastly enzymatic
      degradation. The present report is an attempt to summarize various modes of
      PUFA's metabolism and elaborate biological effects of the associated metabolites
      concerning flaxseed oil.

PMID- 29452257
TI  - Microbiota changes impact on sexually transmitted infections and the development
      of pelvic inflammatory disease.
AB  - The integrity of the human urogenital microbiome is crucial for women's health
      and well-being. An imbalance of the urogenital microbiota increases the risk for
      sexually transmitted infections. In this review, we discuss the microbiota
      composition of the female urogenital tract and its role in protecting from
      sexually transmitted infections and the emergence of pelvic inflammatory disease.

PMID- 29452258
TI  - Recent findings related to immune responses against leptospirosis and novel
      strategies to prevent infection.
AB  - What are the new approaches and emerging ideas to prevent leptospirosis, a
      neglected bacterial re-emerging zoonotic disease? How do Leptospira interrogans
      escape the host defenses? We aim here to review and discuss the most recent
      literature that provides some answers to these questions, in particular data
      related to a better understanding of adaptive and innate immunity towards
      leptospires, and design of vaccines. This is an opinion paper, not a
      comprehensive review. We will try to highlight the new strategies and
      technologies boosting the search for drugs and vaccines. We will also address the
      bottlenecks and difficulties impairing the search for efficient vaccines and the
      many gaps in our knowledge of immunity against leptospirosis. Finally, we aim to
      delineate how Leptospira spp. escape the innate immune responses of Toll-Like
      receptors (TLR) and Nod-Like receptors (NLR). The rational use of TLR and NLR
      agonists as adjuvants could be key to design future vaccines against pathogenic
      leptospires.

PMID- 29452259
TI  - Real-world evaluation of a mobile health application in children with asthma.
AB  - BACKGROUND: Mobile health applications for asthma are increasingly being
      developed. However, there are no published randomized controlled trials
      evaluating efficacy in decreasing exacerbations. OBJECTIVE: To evaluate the
      impact of a mobile asthma application for asthma-related urgent health care
      usage. METHODS: We conducted a 6-month prospective randomized controlled trial
      for patients (6 months-21 years old) with persistent asthma presenting with an
      asthma exacerbation to the emergency department of a pediatric academic medical
      center. Participants were randomized to AsthmaCare (application providing
      medication and trigger reminders and treatment plan) or the control (online
      asthma information). Primary outcome measures were comparison of emergency
      department and urgent care visits and hospitalizations 6 months before and after
      randomization. RESULTS: AsthmaCare participants (n = 98) were slightly older
      (7.84 vs 6.24 years; P = .02) than controls (n = 95) but similar for sex (55% vs
      62% boys), race (83% vs 77% African American), and insurer (89% vs 98% Medicaid).
      The 2 groups were similar in having more than 2 comorbidities (34% vs 32%) and
      receiving National Heart, Lung, and Blood Institute step 3 treatment or higher
      (69% vs 57%). There was no significant decrease in emergency department or urgent
      care visits or hospitalizations between the intervention and control groups.
      AsthmaCare participants were more likely to report improvement in asthma
      management 6 months after study enrollment (79% vs 64%; P = .06). CONCLUSION:
      This randomized controlled trial did not demonstrate a significant decrease in
      asthma-related emergency department visits or hospitalizations among children who
      used a mobile health application. TRIAL REGISTRATION: ClinicalTrials.gov,
      Identifier NCT02333630.

PMID- 29452260
TI  - The highs and lows of marijuana use in allergy.

PMID- 29452261
TI  - Maternal betaine administration modulates hepatic type 1 iodothyronine deiodinase
      (Dio1) expression in chicken offspring through epigenetic modifications.
AB  - As a feed additive, betaine is widely used in livestock production for its
      ability to promote growth. Our previous studies had reported that maternal
      betaine supplementation altered hepatic metabolism in offspring. But it remains
      unknown whether and how maternal betaine modulates metabolism of thyroid hormones
      in the offspring chickens by epigenetic modification. In this study, one hundred
      and twenty Rugao yellow-feathered laying hens were randomly divided into two
      groups, and were fed basal diet with or without 0.5% betaine supplementation for
      28 days. After that, all the hens were artificially inseminated and then four
      hundreds fertilized eggs were selected. After hatching, the newborn chicks were
      raised until 56 days old. Betaine fed female chicks showed significantly lower
      body weight and lower level of biologically active thyroid hormone in plasma
      compared to control group, which was associated with significantly decrease in
      expression of type 1 iodothyronine deiodinase (Dio1). Moreover, betaine also
      changed hepatic expression of betaine-homocysteine -S-methyltransferase (BHMT)
      and DNA methyltransferase 1 (DNMT1), which may contribute to hypermethylation of
      the Dio1 promoter. Interestingly, betaine treatments of hens caused none of these
      effects in male chicks except Dio1 expression. These results indicate that
      maternal betaine administration effects growth of offspring through differential
      modification of Dio1 gene methylation and expression in liver and this model of
      transgenerational effects may help elucidate the mechanisms of maternal effects
      arise in natural systems.

PMID- 29452262
TI  - Preventing Postoperative Atrial Fibrillation: Is There One Best Option?

PMID- 29452263
TI  - Awake TEVAR for Ruptured Thoracic Aneurysms: Less Is More?

PMID- 29452264
TI  - Antagonists to TRPV1, ASICs and P2X have a potential role to prevent the
      triggering of regional bone metabolic disorder and pain-like behavior in tail
      suspended mice.
AB  - Our recent studies demonstrated that regional bone loss in the unloaded hind
      limbs of tail-suspended mice triggered pain-like behaviors due to the acidic
      environment in the bone induced by osteoclast activation. The aims of the present
      study were to examine whether TRPV1, ASIC and P2X (known as nociceptors) are
      expressed in bone, and whether the antagonists to those receptors affect the
      expression of osteoblast and osteoclast regulators, and prevent the triggering of
      not only pain-like behaviors but also high bone turnover conditions in tail
      suspension model mice. The hind limb-unloaded mice were subjected to tail
      suspension with the hind limbs elevated for 14days. The effects of the TRPV1,
      ASIC3, P2X2/3 antagonists on pain-like behaviors as assessed by the von Frey
      test, paw flick test and spontaneous pain scale; the expressions of TRPV1, ASICs,
      and P2X2 in the bone; and the effects of those antagonists on osteoblast and
      osteoclast regulators were examined. In addition, we evaluated the preventive
      effect of continuous treatment with a TRPV1 antagonist on the trigger for pain
      like behavior and bone loss in tail-suspended mice. Pain-like behaviors were
      significantly improved by the treatment with TRPV1, ASIC, P2X antagonists; TRPV1,
      ASICs and P2X were expressed in the bone tissues; and the antagonists to these
      receptors down-regulated the expression of osteoblast and osteoclast regulators
      in tail-suspended mice. In addition, continuous treatment with a TRPV1 antagonist
      during tail-suspension prevented the induction of pain-like behaviors and
      regional bone loss in the unloaded hind limbs. We, therefore, believe that those
      receptor antagonists have a potential role in preventing the triggering of
      skeletal pain with associated regional bone metabolic disorder.

PMID- 29452265
TI  - Characterizing the modulation of resting-state fMRI metrics by baseline
      physiology.
AB  - The blood-oxygenation level dependent (BOLD) functional magnetic resonance
      imaging (fMRI) signal is commonly used to assess functional connectivity across
      brain regions, particularly in the resting state (rs-fMRI). However, the BOLD
      fMRI signal is not merely a representation of neural activity, but a combination
      of neural activity and vascular response. These aspects of the BOLD signal are
      easily influenced by systemic physiology, potentially biasing BOLD-based
      functional connectivity measurements. In this work, we focus on the following
      physiological modulators of the BOLD signal: cerebral blood flow (CBF), venous
      blood oxygenation, and cerebrovascular reactivity (CVR). We use simulations and
      experiments to examine the relationship between the physiological parameters and
      rs-fMRI functional connectivity measurements in three resting-state networks:
      default mode network, somatosensory network and visual network. By using the
      general linear model, we demonstrate that physiological modulators significantly
      impact functional connectivity measurements in these regions, but in a manner
      that depends on the interplay between signal- and noise-driven correlations.
      Moreover, we find that the physiological effects vary by brain region and depend
      on the range of physiological conditions probed; the associations are more
      complex than previously reported. The results confirm that it is important to
      account for the effect of physiological modulators when comparing resting-state
      fMRI metrics. We note that such modulatory effects may be amplified by disease
      conditions, which will warrant future investigations.

PMID- 29452266
TI  - Healthy brain aging: Interplay between reactive species, inflammation and energy
      supply.
AB  - Brains' high energy expenditure with preferable utilization of glucose and ketone
      bodies, defines the specific features of its energy homeostasis. The extensive
      oxidative metabolism is accompanied by a concomitant generation of high amounts
      of reactive oxygen, nitrogen, and carbonyl species, which will be here
      collectively referred to as RONCS. Such metabolism in combination with high
      content of polyunsaturated fatty acids creates specific problems in maintaining
      brains' redox homeostasis. While the levels of products of interaction between
      RONCS and cellular components increase slowly during the first two trimesters of
      individuals' life, their increase is substantially accelerated towards the end of
      life. Here we review the main mechanisms controlling the redox homeostasis of the
      mammalian brain, their age-dependencies as well as their adaptive potential,
      which might turn out to be much higher than initially assumed. According to
      recent data, the organism seems to respond to the enhancement of aging-related
      toxicity by forming a new homeostatic set point. Therefore, further research will
      focus on understanding the properties of the new set point(s), the general nature
      of this phenomenon and will explore the limits of brains' adaptivity.

PMID- 29452267
TI  - GIT2-A keystone in ageing and age-related disease.
AB  - Since its discovery, G protein-coupled receptor kinase-interacting protein 2,
      GIT2, and its family member, GIT1, have received considerable interest concerning
      their potential key roles in regulating multiple inter-connected physiological
      and pathophysiological processes. GIT2 was first identified as a multifunctional
      protein that is recruited to G protein-coupled receptors (GPCRs) during the
      process of receptor internalization. Recent findings have demonstrated that
      perhaps one of the most important effects of GIT2 in physiology concerns its role
      in controlling multiple aspects of the complex ageing process. Ageing can be
      considered the most prevalent pathophysiological condition in humans, affecting
      all tissue systems and acting as a driving force for many common and intractable
      disorders. The ageing process involves a complex interplay among various
      deleterious activities that profoundly disrupt the body's ability to cope with
      damage, thus increasing susceptibility to pathophysiologies such as
      neurodegeneration, central obesity, osteoporosis, type 2 diabetes mellitus and
      atherosclerosis. The biological systems that control ageing appear to function as
      a series of interconnected complex networks. The inter-communication among
      multiple lower-complexity signaling systems within the global ageing networks is
      likely coordinated internally by keystones or hubs, which regulate responses to
      dynamic molecular events through protein-protein interactions with multiple
      distinct partners. Multiple lines of research have suggested that GIT2 may act as
      one of these network coordinators in the ageing process. Identifying and
      targeting keystones, such as GIT2, is thus an important approach in our
      understanding of, and eventual ability to, medically ameliorate or interdict age
      related progressive cellular and tissue damage.

PMID- 29452268
TI  - High Prevalence of Liver Fibrosis Among European Adults With Unknown Liver
      Disease: A Population-Based Study.
AB  - BACKGROUND & AIMS: Liver fibrosis is the main determinant of long-term outcome in
      chronic liver diseases. Little is known about the prevalence of liver fibrosis in
      the general population. The aim of the study was to investigate the prevalence of
      liver fibrosis in the general adult population with unknown liver disease.
      METHODS: This was a population-based, cross-sectional study performed in the
      Barcelona metropolitan area. Subjects aged 18 to 75 years old were identified
      randomly from citizens included in the primary health care registry. Of 4866
      subjects invited, 3076 participated (63.2%). Liver fibrosis was estimated by
      measuring liver stiffness (LS) with transient elastography (TE). Liver histology
      was assessed in 92 subjects with increased LS. RESULTS: Prevalence estimates of
      increased LS (>=6.8, >=8.0, and >=9.0 kPa) were 9.0%, 5.8%, and 3.6%,
      respectively. The etiology of liver disease was mainly nonalcoholic fatty liver
      disease (NAFLD), followed by alcohol risk consumption (consumption of >=21
      standard drinking units/wk in men and >=14 standard drinking units/wk in women).
      Factors independently associated with increased LS were male sex, abdominal
      obesity, type 2 diabetes, serum glucose, high-density lipoprotein, and
      triglyceride levels. Subjects without risk factors for NAFLD or without alcohol
      risk consumption had a very low prevalence of increased LS. The best cut-off
      value of LS for significant liver fibrosis (F2-F4) was 9.2 kPa, with high
      sensitivity and specificity. TE was more accurate than alanine aminotransferase,
      NAFLD fibrosis score, or Fibrosis 4. An algorithm for screening for liver
      fibrosis using TE in the community setting is proposed. CONCLUSIONS: These
      findings show a high prevalence of silent liver disease with advanced fibrosis
      mainly related to NAFLD in adult European subjects without known liver disease.
      An LS value less than 9.2 kPa predicts the absence of significant liver fibrosis
      with high accuracy and could be used for screening purposes.

PMID- 29452269
TI  - Progress in Radiotherapy for Regional and Oligometastatic Disease in 2017.
AB  - This review highlights key publications and abstracts in the field of radiation
      oncology for lung cancer in 2017 and attempts to place these in the context of
      developments for the broader thoracic oncology community.

PMID- 29452270
TI  - High-level extracellular production of Rhizopus oryzae lipase in Pichia pastoris
      via a strategy combining optimization of gene-copy number with co-expression of
      ERAD-related proteins.
AB  - Rhizopus oryzae lipase (ROL) is an important industrial enzyme limited in
      application due to its low production in native strains. Here, we used a new
      combined strategy to overexpress ROL in Pichia pastoris. An efficient method
      based on bio-brick was developed to construct a series of vectors harboring
      different copy numbers of ROL gene cassettes, which were then transformed into P.
      pastoris GS115 to generate a strain with specific copy numbers of ROL. An
      optimized gene-dosage recombinant strain of GS115/pAOalpha-5ROL 11# harboring
      five copies of ROL was screened, revealing production of the highest activity
      (2700 U/mL), which was 8-fold higher than that of the strain harboring one copy.
      The activity of GS115/pAOalpha-5ROL 11# was then enhanced to 3080 U/mL in a
      shaking flask under optimized culture conditions. Subsequently, the endoplasmic
      reticulum-associated protein-degradation-related genes Ubc1 or/and Hrd1 were co
      expressed with ROL to further increase ROL expression. The activities of the
      recombinant strains, GS115/5ROL-Ubc1 22#, -Hrd1 15#, and -Hrd1-Ubc1 1#, were 4000
      U/mL, 4200 U/mL, and 4750 U/mL, which was 29.9%, 36.4%, and 54.2% higher,
      respectively, than that observed in GS115/pAOalpha-5ROL 11#. Using the combined
      strategy, ROL expression was improved 15.8-fold, with maximum GS115/5ROL-Hrd1
      Ubc1 1# activity reaching 33,900 U/mL via a sorbitol/methanol co-feeding strategy
      in a 3-L fermenter and resulting in a 1.65-, 1.26-, and 1.14-fold enhancement
      relative to the activities observed in strains GS115/pAOalpha-5ROL 11#,
      GS115/5ROL-Ubc1 22#, and GS115/5ROL-Hrd1 15#, respectively. These results
      indicated that heterologous overexpression of ROL in P. pastoris using this
      combined strategy is feasible for large-scale industrialization.

PMID- 29452271
TI  - Biotechnologically produced chitosan for nanoscale products. A legal analysis.
AB  - Conventionally, chitosans are derived from shrimp and other crustacean shells.
      Biotechnology offers an alternative route to produce chitosans and more
      importantly, specific chitosan structures tailored to the needs of a diversity of
      industries. However, for biotech chitosans and products thereof to be
      commercialised, legislation should not create a burden. Here, the requirements of
      the EU regulatory framework have been analysed for the entire chain from research
      to development and production of several potential applications including
      nanomaterials. The animal or biotechnological origin leads to specific
      requirements in production of the raw material. No EU legislation dedicated to
      nanomaterials has been adopted. Instead, products are governed under the
      respective existing product legislation subject to extra requirements for safety
      assessment. While a knowledge gap exists on hazards related to nanomaterials in
      general, there is a need to establish realistic regulatory study designs to
      assess the safety of specific products. Furthermore, as many of the existing
      chitosan applications are not considered nanomaterials, it would be
      discriminatory to treat biotechnology derived products differently.

PMID- 29452272
TI  - pH-sensitive doxorubicin-conjugated prodrug micelles with charge-conversion for
      cancer therapy.
AB  - : Intelligent drug delivery systems with prolonged circulation time, reduced drug
      leakage in blood, target site-triggered drug release and endosomal escape are
      attractive and ideal for malignant tumor therapy. Herein, doxorubicin (DOX)
      conjugated smart polymeric micelles based on 4-carboxy benzaldehyde-grafted poly
      (L-lysine)-block-poly (methacryloyloxyethyl phosphorylcholine) (PLL(CB/DOX)-b
      PMPC) copolymer are prepared. DOX and electronegative 4-carboxy benzaldehyde are
      conjugated to the PLL block via an imine linkage and as a result, the drug loaded
      micelles exhibited the pH-triggered charge-conversion property and accelerated
      drug release at tumor pH. In vitro cytotoxicity studies of these DOX-loaded
      micelles exhibited great tumor inhibition against HeLa and 4T1 cells. Moreover,
      in mice models of breast cancer, these DOX-loaded micelles showed better anti
      tumor efficacy and less organ toxicity than free drug. In summary, these
      polymeric micelles could be applied as potential nanocarriers for cancer therapy.
      STATEMENT OF SIGNIFICANCE: As a typical anti-cancer drug, Doxorubicin (DOX)
      exhibited remarkable tumor inhibition but was limited by its low drug utilization
      and strong toxicity to organs. To overcome these challenges, we developed a DOX
      conjugated polymeric micelle as a nano drug carrier which was endowed with pH
      sensitivity and charge-conversion function. The structure of micelles would
      quickly disintegrate with surface charge-conversion in acidic environment, which
      would contribute to the endosomal escape and accelerated drug release. These DOX
      conjugated micelles would provide a promising platform for the efficient DOX
      delivery and better anti-cancer efficiency.

PMID- 29452274
TI  - Control of thiol-maleimide reaction kinetics in PEG hydrogel networks.
AB  - : Michael-type addition reactions are widely used to polymerize biocompatible
      hydrogels. The thiol-maleimide modality achieves the highest macromer coupling
      efficiency of the reported Michael-type pairs, but the resulting hydrogel
      networks are heterogeneous because polymerization is faster than the individual
      components can be manually mixed. The reactivity of the thiol dictates the
      overall reaction speed, which can be slowed in organic solvents and acidic
      buffers. Since these modifications also reduce the biocompatibility of resulting
      hydrogels, we investigated a series of biocompatible buffers and crosslinkers to
      decelerate gelation while maintaining high cell viability. We found that lowering
      the polymer weight percentage (wt%), buffer concentration, and pH slowed gelation
      kinetics, but crosslinking with an electronegative peptide was optimal for both
      kinetics and cell viability. Including a high glucose medium supplement in the
      polymer solvent buffer improved the viability of the cells being encapsulated
      without impacting gelation time. Slowing the speed of polymerization resulted in
      more uniform hydrogels, both in terms of visual inspection and the diffusion of
      small molecules through the network. However, reactions that were too slow
      resulted in non-uniform particle dispersion due to settling, thus there is a
      trade-off in hydrogel network uniformity versus cell distribution in the
      hydrogels when using these networks in cell applications. STATEMENT OF
      SIGNIFICANCE: The polymer network of thiol-maleimide hydrogels assembles faster
      than individual components can be uniformly mixed due to their fast gelation
      kinetics. The lack of homogeneity can result in variable cell-based assay
      results, resulting in batch-to-batch variability and limiting their use in
      predictive screening assays. Although these hydrogels are incredibly useful in
      tissue engineering, this network heterogeneity is a known problem in the field.
      We screened a variety of possible techniques to slow down the reaction speed and
      improve the homogeneity of these hydrogels, without sacrificing the viability and
      distribution of encapsulated cells. As others have reported, an electronegative
      crosslinker was the most effective technique to slow the reaction, but the
      chemical modification required is technically challenging. Of interest to a broad
      community, we screened buffer type, strength, and crosslinker electronegativity
      to find an optimal reaction speed that allows for high cell viability and small
      molecule diffusion, without allowing cells to settle during gelation, allowing
      application of these materials to the drug screening industry and tissue
      engineering community.

PMID- 29452275
TI  - A laser-activated multifunctional targeted nanoagent for imaging and gene therapy
      in a mouse xenograft model with retinoblastoma Y79 cells.
AB  - : Retinoblastoma (RB) is the most common intraocular malignancy of childhood that
      urgently needs early detection and effective therapy methods. The use of
      nanosized gene delivery systems is appealing because of their highly adjustable
      structure to carry both therapeutic and imaging agents. Herein, we report a folic
      acid (FA)-modified phase-changeable cationic nanoparticle encapsulating liquid
      perfluoropentane (PFP) and indocyanine green (ICG) (FA-CN-PFP-ICG, FCNPI) with
      good plasmid DNA (pDNA) carrying capacity, favorable biocompatibility, excellent
      photoacoustic (PA) and ultrasound (US) contrast, enhanced gene transfection
      efficiency and therapeutic effect. The liquid-gas phase transition of the FCNPI
      upon laser irradiation has provided splendid contrasts for US/PA dual-modality
      imaging in vitro as well as in vivo. More importantly, laser-mediated gene
      transfection with targeted cationic FCNPI nanoparticles demonstrated the best
      therapeutic effect compared with untargeted cationic nanoparticle (CN-PFP-ICG,
      CNPI) and neutral nanoparticle (NN-PFP-ICG, NNPI), both in vitro and in vivo.
      Such a multifunctional nanoagent is expected to combine dual-mode guided imaging
      with fewer side effects and proper therapeutic efficacy. These results establish
      an experimental foundation for the clinical detection of and therapy for RB.
      STATEMENT OF SIGNIFICANCE: We successfully constructed a multifunctional targeted
      cationic nanoparticle (FCNPI) and meticulously compared the variations in the
      plasmid loading capacity and binding to Y79 cells with NNPI, CNPI, and FCNPI.
      FCNPI exhibited favorable plasmid loading capability, splendid ability for
      targeting and only it could provide optimal US and PA contrast to background
      during a considerable long time. The FCNPI/pDNA + Laser system also exhibited the
      best therapeutic effect in vivo; this finding proposes a potential strategy for
      the evaluation of an efficient gene delivery nanocarrier for gene targeting
      therapy of RB tumor. Our study showed that there are great advantages of
      targeting FCNPI to provide PA/US imaging and to enlighten laser-mediated gene
      transfection. FCNPI is a very helpful multifunctional agent with potential.

PMID- 29452273
TI  - 3D bioprinted functional and contractile cardiac tissue constructs.
AB  - : Bioengineering of a functional cardiac tissue composed of primary
      cardiomyocytes has great potential for myocardial regeneration and in vitro
      tissue modeling. However, its applications remain limited because the cardiac
      tissue is a highly organized structure with unique physiologic, biomechanical,
      and electrical properties. In this study, we undertook a proof-of-concept study
      to develop a contractile cardiac tissue with cellular organization, uniformity,
      and scalability by using three-dimensional (3D) bioprinting strategy. Primary
      cardiomyocytes were isolated from infant rat hearts and suspended in a fibrin
      based bioink to determine the priting capability for cardiac tissue engineering.
      This cell-laden hydrogel was sequentially printed with a sacrificial hydrogel and
      a supporting polymeric frame through a 300-um nozzle by pressured air. Bioprinted
      cardiac tissue constructs had a spontaneous synchronous contraction in culture,
      implying in vitro cardiac tissue development and maturation. Progressive cardiac
      tissue development was confirmed by immunostaining for alpha-actinin and connexin
      43, indicating that cardiac tissues were formed with uniformly aligned, dense,
      and electromechanically coupled cardiac cells. These constructs exhibited
      physiologic responses to known cardiac drugs regarding beating frequency and
      contraction forces. In addition, Notch signaling blockade significantly
      accelerated development and maturation of bioprinted cardiac tissues. Our results
      demonstrated the feasibility of bioprinting functional cardiac tissues that could
      be used for tissue engineering applications and pharmaceutical purposes.
      STATEMENT OF SIGNIFICANCE: Cardiovascular disease remains a leading cause of
      death in the United States and a major health-care burden. Myocardial infarction
      (MI) is a main cause of death in cardiovascular diseases. MI occurs as a
      consequence of sudden blocking of blood vessels supplying the heart. When
      occlusions in the coronary arteries occur, an immediate decrease in nutrient and
      oxygen supply to the cardiac muscle, resulting in permanent cardiac cell death.
      Eventually, scar tissue formed in the damaged cardiac muscle that cannot conduct
      electrical or mechanical stimuli thus leading to a reduction in the pumping
      efficiency of the heart. The therapeutic options available for end-stage heart
      failure is to undergo heart transplantation or the use of mechanical ventricular
      assist devices (VADs). However, many patients die while being on a waiting list,
      due to the organ shortage and limitation of VADs, such as surgical complications,
      infection, thrombogenesis, and failure of the electrical motor and hemolysis.
      Ultimately, 3D bioprinting strategy aims to create clinically applicable tissue
      constructs that can be immediately implanted in the body. To date, the focus on
      replicating complex and heterogeneous tissue constructs continues to increase as
      3D bioprinting technologies advance. In this study, we demonstrated the
      feasibility of 3D bioprinting strategy to bioengineer the functional cardiac
      tissue that possesses a highly organized structure with unique physiological and
      biomechanical properties similar to native cardiac tissue. This bioprinting
      strategy has great potential to precisely generate functional cardiac tissues for
      use in pharmaceutical and regenerative medicine applications.

PMID- 29452277
TI  - Association Between Obesity and Acute Severity Among Patients Hospitalized for
      Asthma Exacerbation.
AB  - BACKGROUND: Although studies have demonstrated relations between obesity and
      incident asthma, little is known about the association of obesity with acute
      severity in adults hospitalized for asthma exacerbation. OBJECTIVES: To
      investigate the association of obesity with acute severity of asthma
      exacerbation. METHODS: This is a retrospective cohort study using population
      based data of 8 geographically diverse US states from 2010 through 2013. We
      included adults (age 18-54 years) hospitalized for asthma exacerbation. The
      outcome measures were markers of acute severity-use of mechanical ventilation
      (defined by noninvasive positive pressure ventilation and/or invasive mechanical
      ventilation) and hospital length of stay. To determine the association of obesity
      with each outcome, we fit multivariable models adjusting for patient-level
      confounders (eg, age, sex, race/ethnicity, primary insurance, quartiles for
      household income, residential status, and comorbidities) and potential patient
      clustering within hospitals. RESULTS: Among the 72,086 patients hospitalized for
      asthma exacerbation, 24% were obese. Obesity was associated with a significantly
      higher risk of any mechanical ventilation use (8.3% vs 5.0%; adjusted odds ratio
      [OR], 1.77; 95% CI, 1.63-1.92; P < .001) driven by the higher risk of noninvasive
      positive pressure ventilation use (7.2% vs 3.4%; adjusted OR, 2.14; 95% CI, 1.96
      2.35; P < .001). Likewise, obese patients were more likely to have a hospital
      length of stay of 3 or more days compared with nonobese patients (59.4% vs 46.5%;
      adjusted OR, 1.37; 95% CI, 1.32-1.43; P < .001). These findings were consistent
      with stratifications by age, sex, and race/ethnicity. CONCLUSIONS: In this
      population-based study of adults hospitalized for asthma exacerbation, obesity
      was associated with higher acute severity.

PMID- 29452278
TI  - G-quadruplexes in Prague: A Bohemian Rhapsody.
AB  - The Sixth International Meeting on Quadruplex Nucleic Acids was held at the Hotel
      Internationale in Prague, Czech Republic from 31 May - 3 June 2017. A vibrant
      interdisciplinary community of over 300 scientists gathered to share their newest
      results in this exciting field and exchange ideas for further investigations.

PMID- 29452279
TI  - Biophysical methods: Complementary tools to study the influence of human steroid
      hormones on the liposome membrane properties.
AB  - Human steroid hormones are involved in many aspects of physiology and have long
      been known to exert rapid and delayed effects. They are lipophilic molecules
      which can be incorporated into the lipid membranes. Through non-covalent
      interactions they can alter the properties of the membrane, including fluidity,
      lipid raft formation and others. In this review, different biophysical techniques
      were described to study the interaction of human steroid hormones with biological
      and biomimetic membranes such as differential scanning calorimetry, electron
      paramagnetic resonance, fluorescence spectroscopy and Fourier transform infrared
      spectroscopy. The aim of this review is to overview the results of these
      complementary biophysical techniques summarizing the effects of these hormones on
      thermotropic and dynamic membrane properties. Meanwhile, the disorder induced by
      human steroid hormones is discussed in terms of hydrophobicity and chemical
      structure.

PMID- 29452280
TI  - Sticholysin II-mediated cytotoxicity involves the activation of regulated
      intracellular responses that anticipates cell death.
AB  - Sticholysin II (StII) is a pore-forming toxin of biomedical interest that belongs
      to the actinoporin protein family. Sticholysins are currently under examination
      as an active immunomodulating component of a vaccinal platform against tumoral
      cells and as a key element of a nucleic acids delivery system to cell cytosol.
      These proteins form pores in the plasma membrane leading to ion imbalance and
      cell lysis. However, the intracellular mechanisms triggered by actinoporins upon
      binding to membranes and its consequences for cell death are barely understood.
      Here, we have examined the cytotoxicity and intracellular responses induced by
      StII upon binding to human B-cell lymphoma Raji in vitro. StII cytotoxicity
      involves a functional actin cytoskeleton, induces cellular swelling, lysis and
      the concomitant release of cytosol content. In addition, StII induces calcium
      release mainly from the Endoplasmic Reticulum, activates Mitogen-Activated
      Protein Kinase ERK and impairs mitochondrial membrane potential. Furthermore,
      StII stimulates the expression of receptor interacting protein kinase 1 (RIP1),
      normally related to different forms of regulated cell death such as apoptosis and
      necroptosis. In correspondence, necrostatin-1, an inhibitor of this kinase,
      reduces StII cytotoxicity. However, the mechanism of cell death activated by StII
      does not involve caspases activation, typical molecular features of apoptosis and
      pyroptosis. Our results suggest that, beyond pore-formation and cell lysis, StII
      induced cytotoxicity could involve other regulated intracellular mechanisms
      connected to RIP1-MEK1/2 -ERK1/2- pathways. This opens new perspectives and
      challenges the general point of view that these toxins induce a completely
      unregulated mechanism of necrotic cell death. This study contributes to a better
      understanding of the molecular mechanisms involved in toxin-cell interaction and
      the implications for cell functioning, with connotation for the exploitations of
      these toxins in clinical settings.

PMID- 29452276
TI  - Application of targeted mass spectrometry in bottom-up proteomics for systems
      biology research.
AB  - The enormous diversity of proteoforms produces tremendous complexity within
      cellular proteomes, facilitates intricate networks of molecular interactions, and
      constitutes a formidable analytical challenge for biomedical researchers.
      Currently, quantitative whole-proteome profiling often relies on non-targeted
      liquid chromatography-mass spectrometry (LC-MS), which samples proteoforms
      broadly, but can suffer from lower accuracy, sensitivity, and reproducibility
      compared with targeted LC-MS. Recent advances in bottom-up proteomics using
      targeted LC-MS have enabled previously unachievable identification and
      quantification of target proteins and posttranslational modifications within
      complex samples. Consequently, targeted LC-MS is rapidly advancing biomedical
      research, especially systems biology research in diverse areas that include
      proteogenomics, interactomics, kinomics, and biological pathway modeling. With
      the recent development of targeted LC-MS assays for nearly the entire human
      proteome, targeted LC-MS is positioned to enable quantitative proteomic profiling
      of unprecedented quality and accessibility to support fundamental and clinical
      research. Here we review recent applications of bottom-up proteomics using
      targeted LC-MS for systems biology research. SIGNIFICANCE: Advances in targeted
      proteomics are rapidly advancing systems biology research. Recent applications
      include systems-level investigations focused on posttranslational modifications
      (such as phosphoproteomics), protein conformation, protein-protein interaction,
      kinomics, proteogenomics, and metabolic and signaling pathways. Notably, absolute
      quantification of metabolic and signaling pathway proteins has enabled accurate
      pathway modeling and engineering. Integration of targeted proteomics with other
      technologies, such as RNA-seq, has facilitated diverse research such as the
      identification of hundreds of "missing" human proteins (genes and transcripts
      that appear to encode proteins but direct experimental evidence was lacking).

PMID- 29452281
TI  - Incidence and risk factors of postoperative neurologic decline after complex
      adult spinal deformity surgery: results of the Scoli-RISK-1 study.
AB  - BACKGROUND CONTEXT: Significant variability in neurologic outcomes after surgical
      correction for adult spinal deformity (ASD) has been reported. Risk factors for
      decline in neurologic motor outcomes are poorly understood. PURPOSE: The
      objective of the present investigation was to identify the risk factors for
      postoperative neurologic motor decline in patients undergoing complex ASD
      surgery. STUDY DESIGN/SETTING: This is a prospective international multicenter
      cohort study. PATIENT SAMPLE: From September 2011 to October 2012, 272 patients
      undergoing complex ASD surgery were prospectively enrolled in a multicenter,
      international cohort study in 15 sites. OUTCOME MEASURES: Neurologic decline was
      defined as any postoperative deterioration in American Spinal Injury Association
      lower extremity motor score (LEMS) compared with preoperative status. METHODS: To
      identify risk factors, 10 candidate variables were selected for univariable
      analysis from the dataset based on clinical relevance, and a multivariable
      logistic regression analysis was used with backward stepwise selection. RESULTS:
      Complete datasets on 265 patients were available for analysis and 61 (23%)
      patients showed a decline in LEMS at discharge. Univariable analysis showed that
      the key factors associated with postoperative neurologic deterioration included
      older age, lumbar-level osteotomy, three-column osteotomy, and larger blood loss.
      Multivariable analysis revealed that older age (odds ratio [OR]=1.5 per 10 years,
      95% confidence interval [CI] 1.1-2.1, p=.005), larger coronal deformity angular
      ratio [DAR] (OR=1.1 per 1 unit, 95% CI 1.0-1.2, p=.037), and lumbar osteotomy
      (OR=3.3, 95% CI 1.2-9.2, p=.022) were the three major predictors of neurologic
      decline. CONCLUSIONS: Twenty-three percent of patients undergoing complex ASD
      surgery experienced a postoperative neurologic decline. Age, coronal DAR, and
      lumbar osteotomy were identified as the key contributing factors.

PMID- 29452282
TI  - Load-sharing through elastic micro-motion accelerates bone formation and
      interbody fusion.
AB  - BACKGROUND CONTEXT: Achieving a successful spinal fusion requires the proper
      biological and biomechanical environment. Optimizing load-sharing in the
      interbody space can enhance bone formation. For anterior cervical discectomy and
      fusion (ACDF), loading and motion are largely dictated by the stiffness of the
      plate, which can facilitate a balance between stability and load-sharing. The
      advantages of load-sharing may be substantial for patients with comorbidities and
      in multilevel procedures where pseudarthrosis rates are significant. PURPOSE: We
      aimed to evaluate the efficacy of a novel elastically deformable, continuously
      load-sharing anterior cervical spinal plate for promotion of bone formation and
      interbody fusion relative to a translationally dynamic plate. STUDY
      DESIGN/SETTING: An in vivo animal model was used to evaluate the effects of an
      elastically deformable spinal plate on bone formation and spine fusion. METHODS:
      Fourteen goats underwent an ACDF and received either a translationally dynamic or
      elastically deformable plate. Animals were followed up until 18 weeks and were
      evaluated by plain x-ray, computed tomography scan, and undecalcified histology
      to evaluate the rate and quality of bone formation and interbody fusion. RESULTS:
      Animals treated with the elastically deformable plate demonstrated statistically
      significantly superior early bone formation relative to the translationally
      dynamic plate. Trends in the data from 8 to 18 weeks postoperatively suggest that
      the elastically deformable implant enhanced bony bridging and fusion, but these
      enhancements were not statistically significant. CONCLUSIONS: Load-sharing
      through elastic micro-motion accelerates bone formation in the challenging goat
      ACDF model. The elastically deformable implant used in this study may promote
      early bony bridging and increased rates of fusion, but future studies will be
      necessary to comprehensively characterize the advantages of load-sharing through
      micro-motion.

PMID- 29452283
TI  - Posterolateral fusion (PLF) versus transforaminal lumbar interbody fusion (TLIF)
      for spondylolisthesis: a systematic review and meta-analysis.
AB  - BACKGROUND CONTEXT: Lumbar fusion is an effective and durable treatment for
      symptomatic lumbar spondylolisthesis; however, the current literature provides
      insufficient evidence to recommend an optimal surgical fusion strategy. PURPOSE:
      The present study aims to compare the clinical outcomes, fusion rates, blood
      loss, and operative times between open posterolateral lumbar fusion (PLF) alone
      and open transforaminal lumbar interbody fusion (TLIF) + posterolateral fusion
      for spondylolisthesis. STUDY DESIGN: This is a systematic literature review and
      meta-analysis of English language studies for the treatment of spondylolisthesis
      with PLF versus PLF + TLIF. PATIENT SAMPLE: Data were obtained from published
      randomized controlled trials (RCTs) and retrospective cohort studies. OUTCOME
      MEASURES: Clinical outcomes included Oswestry Disability Index (ODI), back pain,
      leg pain, and health-related quality of life (HRQOL) scores. Fusion rate,
      operative time, blood loss, and infection rate were also assessed. METHODS: A
      literature search of three electronic databases was performed to identify
      investigations performed comparing PLF alone with PLF + TLIF for treatment of low
      grade lumbar spondylolisthesis. The summary effect size was assessed from pooling
      observational studies for each of the outcome variables, with odds ratios (ORs)
      used for fusion and infection rate, mean difference used for improvement in ODI
      and leg pain as well as operative time and blood loss, and standardized mean
      difference used for improvement in back pain and HRQOL outcomes. Studies were
      weighed based on the inverse of the variance and heterogeneity. Heterogeneity was
      assessed using the I2-an estimate of the error caused by between-study variation.
      Effect sizes from the meta-analysis were then compared with data from the RCTs to
      assess congruence in outcomes. RESULTS: The initial literature search yielded 282
      unique, English language studies. Seven were determined to meet our inclusion
      criteria and were included in our qualitative analysis. Five observational
      studies were included in our quantitative meta-analysis. The pooled fusion
      success rates were 84.7% (100/118) in the PLF group and 94.3% (116/123) in the
      TLIF group. Compared with TLIF patients, PLF patients had significantly lower
      odds of achieving solid arthrodesis (OR 0.33, 95% confidence interval [CI] 0.13
      0.82, p=.02; I2=0%). With regard to improvement in back pain, the point estimate
      for the effect size was -0.27 (95% CI -0.43 to -0.10, p=.002; I2=0%), in favor of
      the TLIF group. For ODI, the pooled estimate for the effect size was -3.73 (95%
      CI -7.09 to -0.38, p=.03; I2=35%), significantly in favor of the TLIF group.
      Operative times were significantly shorter in the PLF group, with a summary
      effect size of -25.55 (95% CI -43.64 to -7.45, p<.01; I2=54%). No significant
      difference was observed in leg pain, HRQOL improvement, blood loss, or infection
      rate. Our meta-analysis results were consistent with RCTs, in favor of TLIF for
      achieving radiographic fusion and greater improvement in ODI and back pain.
      CONCLUSIONS: Our results demonstrate that for patients undergoing fusion for
      spondylolisthesis, TLIF is superior to PLF with regard to achieving radiographic
      fusion. However, current data only provide weak support, if any, favoring TLIF
      over PLF for clinical improvement in disability and back pain.

PMID- 29452284
TI  - "Microendoscopic" versus "pure endoscopic" surgery for spinal intradural mass
      lesions: a comparative study and review.
AB  - BACKGROUND CONTEXT: Endoscopy is increasingly being used for minimal invasiveness
      and panoramic visualization, with unclear efficacy and safety among spinal
      intradural mass. OBJECTIVE: The present study aims to compare microendoscopic and
      pure endoscopic surgery for spinal intradural lesions. MATERIALS AND METHODS:
      Spinal intradural lesions operated using endoscopic or access ports were
      categorized into "microendoscopic" (predominant microscope use) or "pure
      endoscopic" (stand-alone endoscopy) surgery, and were studied with respect to
      clinico-radiological features, techniques, perioperative course, histopathology,
      clinical, and radiological outcome at minimum of 3 months. RESULTS: Among 34
      patients studied, the initial 15 had "microendoscopic" surgery, 16 had "pure
      endoscopic" surgery, and 3 had "mixed" use. There were 18 nerve sheath tumors, 6
      meningiomas, 6 cysts, 2 ependymomas, ranging in size from 1.5 to as large as 6.8
      cm (21%>=4 cm), including 4 in craniovertebral junction (CVJ). Intermuscular or
      paraspinous approach was utilized, followed by small bony fenestration or
      interlaminar corridor. Even larger tumors could be excised using expandable ports
      or "sliding delivery" technique. Although visualization of sides and angles was
      better with endoscope, hemostasis and dural closure had steep learning curve,
      necessitating the use of microscope in the initial cases. Clinical improvement
      and radiological resolution could be achieved in all. There was no significant
      difference between the groups. The change in Nurick grade had significant
      correlation with only the dimension of lesion (p=.03) and preoperative grade
      (p=.05). CONCLUSIONS: This is probably the first report of spinal endoscopy for
      intradural tumors in CVJ or as big as 7 cm. Endoscopy is effective and safe for
      even large tumors with better visualization of sides and angles, albeit with
      hemostasis and dural closure having initial learning curve. Wide heterogeneity of
      surgical terminologies in the literature on these procedures warrants consensus
      for uniform reporting.

PMID- 29452285
TI  - Risk factors for perioperative morbidity in spine surgeries of different
      complexities: a multivariate analysis of 1,009 consecutive patients.
AB  - BACKGROUND CONTEXT: There is a broad spectrum of complications during or after
      surgical procedures, with differing incidences reported in the published
      literature. Heterogeneity can be explained by the lack of an established evidence
      based classification system for documentation and classification of complications
      in a standardized manner. PURPOSE: The objective of this study was to identify
      predictive risk factors for perioperative and early postoperative morbidities in
      spine surgeries of different complexities in a large cohort of consecutive
      patients. STUDY DESIGN: This study is a retrospective case series. OUTCOME
      MEASURES: The outcome measures are the occurrence of perioperative and early
      postoperative morbidities. METHODS: A classification of surgical complexity
      (Grades I-III) was created and applied to 1,009 patients who consecutively
      underwent spine surgery at a single university hospital. The incidence and the
      type of perioperative and early postoperative morbidities were documented.
      Multivariate binary logistic regression analyzed risk factors for (1) hospital
      stay of >=10 days, (2) intermediate care unit (IMC) stay of >=24 hours, (3) blood
      loss of >500 mL, and occurrence of a (4) surgical or (5) medical morbidity.
      RESULTS: A deviation from the regular postoperative course (defined as
      "morbidity") included surgical reasons, such as relapse of symptoms of any kind
      (3.3%), wound healing problems (2.4%), implant-associated complications (1.6%),
      postoperative neurologic deficits (1.5%), infection (1.5%), fracture (0.8%), and
      dural tear in need of revision (0.6%). Medical reasons included anemia (1.8%),
      symptomatic electrolyte derailment (1.0%), and cardiac complications (0.7%),
      among others. An independent risk factor associated with a surgical reason for an
      irregular postoperative course was male gender. Risk factors associated with a
      medical reason for an irregular postoperative course were identified as
      preoperatively high creatinine levels, higher blood loss, and systemic steroid
      use. Independent risk factors for a prolonged hospitalization were preoperatively
      high C-reactive protein level, prolonged postoperative IMC stay, and revision
      surgery. Spinal stabilization or fusion surgery, particularly if involving the
      lumbosacral spine, age, and length of surgery were associated with blood loss of
      >500 mL. Higher surgical complexity, involvement of the pelvis in
      instrumentation, American Society of Anesthesiologists Grade >=III, and
      preoperatively higher creatinine levels were associated with a postoperative IMC
      stay of >24 hours. CONCLUSIONS: The present study confirms several modifiable and
      non-modifiable risk factors for perioperative and early postoperative morbidities
      in spine surgery, among which surgical factors (such as complexity, revision
      surgery, and instrumentation, including the pelvis) play a crucial role. A
      classification of surgical complexity is proposed and validated.

PMID- 29452286
TI  - Risk factor analysis of adjacent segment disease requiring surgery after short
      lumbar fusion: the influence of rheumatoid arthritis.
AB  - BACKGROUND CONTEXT: The influence of rheumatoid arthritis (RA) on the lumbar
      spine has received relatively little attention compared with cervical spine, and
      few studies have been conducted for adjacent segment disease (ASD) after lumbar
      fusion in patients with RA. PURPOSE: The present study aims to determine the
      incidence of ASD requiring surgery (ASDrS) after short lumbar fusion and to
      evaluate risk factors for ASDrS, including RA. STUDY DESIGN: This is a
      retrospective cohort study. PATIENT SAMPLE: The present study included 479
      patients who underwent lumbar spinal fusion of three or fewer levels, with the
      mean follow-up period of 51.2 (12-132) months. OUTCOME MEASURES: The development
      of ASD and consequent revision surgery were reviewed using follow-up data.
      METHODS: The ASDrS-free survival rate of adjacent segments was calculated through
      Kaplan-Meier method. The log-rank test and Cox regression analysis were used to
      evaluate risk factors comprising RA, age, gender, obesity, osteoporosis,
      diabetes, smoking, surgical method, and the number of fusion segments. RESULTS:
      After short lumbar fusion, revision surgery for ASD was performed in 37 patients
      (7.7%). Kaplan-Meier analysis predicted that the ASDrS-free survival rate of
      adjacent segments was 97.8% at 3 years, 92.7% at 5 years, and 86.8% at 7 years.
      In risk factor analysis, patients with RA showed a 4.5 times higher risk of ASDrS
      than patients without RA (p<.001), and patients with three-segment fusion showed
      a 2.7 times higher risk than patients with one- or two-segment fusion (p=.005).
      CONCLUSIONS: Adjacent segment disease requiring surgery was predicted in 13.2% of
      patients at 7 years after short lumbar fusion. Rheumatoid arthritis and the
      number of fusion segments were confirmed as risk factors.

PMID- 29452287
TI  - Dental pulp stem cell-derived chondrogenic cells demonstrate differential cell
      motility in type I and type II collagen hydrogels.
AB  - BACKGROUND CONTEXT: Advances in the development of biomaterials and stem cell
      therapy provide a promising approach to regenerating degenerated discs. The
      normal nucleus pulposus (NP) cells exhibit similar phenotype to chondrocytes.
      Because dental pulp stem cells (DPSCs) can be differentiated into chondrogenic
      cells, the DPSCs and DPSCs-derived chondrogenic cells encapsulated in type I and
      type II collagen hydrogels can potentially be transplanted into degenerated NP to
      repair damaged tissue. The motility of transplanted cells is critical because the
      cells need to migrate away from the hydrogels containing the cells of high
      density and disperse through the NP tissue after implantation. PURPOSE: The
      purpose of this study was to determine the motility of DPSC and DPSC-derived
      chondrogenic cells in type I and type II collagen hydrogels. STUDY
      DESIGN/SETTING: The time lapse imaging that recorded cell migration was analyzed
      to quantify the cell migration velocity and distance. METHODS: The cell viability
      of DPSCs in native or poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S
      StarPEG)-crosslinked type I and type II collagen hydrogels was determined using
      LIVE/DEAD cell viability assay and AlamarBlue assay. DPSCs were differentiated
      into chondrogenic cells. The migration of DPSCs and DPSC-derived chondrogenic
      cells in these hydrogels was recorded using a time lapse imaging system. This
      study was funded by the Regional Institute on Aging and Wichita Medical Research
      and Education Foundation, and the authors declare no competing interest. RESULT:
      DPSCs showed high cell viability in non-crosslinked and crosslinked collagen
      hydrogels. DPSCs migrated in collagen hydrogels, and the cell migration speed was
      not significantly different in either type I collagen or type II collagen
      hydrogels. The migration speed of DPSC-derived chondrogenic cells was higher in
      type I collagen hydrogel than in type II collagen hydrogel. Crosslinking of type
      I collagen with 4S-StarPEG significantly reduced the cell migration speed of DPSC
      derived chondrogenic cells. CONCLUSIONS: After implantation of collagen hydrogels
      encapsulating DPSCs or DPSC-derived chondrogenic cells, the cells can potentially
      migrate from the hydrogels and migrate into the NP tissue. This study also
      explored the differential cell motility of DPSCs and DPSC-derived chondrogenic
      cells in these collagen hydrogels.

PMID- 29452289
TI  - Polypharmacy in people with dementia: Associations with adverse health outcomes.
AB  - Polypharmacy has been linked to higher risks of hospitalisation and death in
      community samples. It is commonly present in people with dementia but these risks
      have rarely been studied in this population. We aimed to investigate associations
      between polypharmacy and emergency department attendance, any and unplanned
      hospitalisation, and mortality in patients with dementia. Using a large mental
      health care database in South London, linked to hospitalisation and mortality
      data, we assembled a retrospective cohort of patients diagnosed with dementia. We
      ascertained number of medications prescribed at the time of dementia diagnosis
      and conducted multivariate Cox regression analyses. Of 4668 patients with
      dementia identified, 1128 (24.2%) were prescribed 4-6 medications and 739 (15.8%)
      >=7 medications. Compared to those using 0-3 medications, patients with dementia
      using 4-6 or >=7 agents had an increased risk of emergency department attendance
      (hazard ratio 1.20/1.35), hospitalisation (hazard ratio 1.12/1.32), unplanned
      hospital admission (hazard ratio 1.12/1.25), and death within two years (hazard
      ratio 1.29/1.39) after controlling for potential confounders. We found evidence
      of a dose response relationship with each additional drug at baseline increasing
      the risk of emergency department attendance and mortality by 5% and
      hospitalisation by 3%. In conclusion, polypharmacy at dementia diagnosis is
      associated with a higher risk of adverse health outcomes. Future research is
      required to elucidate which specific agents underlie this relationship and if
      reduction of inappropriate prescribing is effective in preventing these outcomes
      in dementia.

PMID- 29452290
TI  - Lean body weight is the best scale for venous thromboprophylaxis algorithm in
      severely obese patients undergoing bariatric surgery.
AB  - Severely obese patients undergoing bariatric surgery (BS) are at increased risk
      for venous thromboembolism (VTE). How standard low molecular weight heparin
      (LMWH) regimen should be adapted to provide both sufficient efficacy and safety
      in this setting is unclear. We aimed to compare the influence of four body size
      descriptors (BSD) on peak anti-Xa levels in BS obese patients receiving LMWH
      fixed doses to identify which one had the greatest impact. One hundred and
      thirteen BS obese patients [median body mass index (BMI), 43.3 kg/m2 (IQR, 40.6
      48.7 kg/m2)] receiving subcutaneous dalteparin 5000 IU twice daily were included
      in this prospective monocenter study. Peak steady-state anti-Xa levels were
      measured peri-operatively following thromboprophylaxis initiation. Only 48% of
      patients achieved target anti-Xa levels (0.2-0.5 IU/ml). In univariate analysis,
      age, gender, total body-weight (TBW), lean body-weight (LBW), ideal body-weight
      (IBW), BMI and estimated glomerural filtration rate (eGFR) were associated with
      anti-Xa levels. The strongest negative association was observed with LBW (r = 
      0.56, p < .0001). Receiver operating characteristic curves indicated that among
      BSD, LBW (cut-off >55.8 kg) had the highest sensitivity (73%) and specificity
      (69%) to predict sub-prophylactic anti-Xa levels. In multivariate analysis, LBW
      and eGFR remained associated with anti-Xa levels (beta = -0.47 +/- 0.08, p <
      .0001 and beta = -0.19 +/- 0.08; p = .02, respectively). In BS morbidly obese
      patients receiving LMWH for thromboprophylaxis after BS, LBW and eGFR are the
      main determinants of anti-Xa level, and could be proposed in LMWH-based
      thromboprophylaxis dosing algorithms. The efficacy of a LBW-scale based dosing
      algorithm for optimal VTE prevention deserves further prospective randomized
      trials.

PMID- 29452291
TI  - Pharmacokinetic models to assist the prescriber in choosing the best tacrolimus
      dose.
AB  - Due to a high inter-individual variability in its pharmacokinetics, tacrolimus
      dose individualization is mandatory. Even though the expert opinion has defined
      the area under the curve (AUC) as the best marker to use when performing dose
      adjustment of tacrolimus, most centres only use trough levels. Multiple targets
      have been proposed for this parameter and physicians rely largely on their
      personal experience when making a decision about dose adjustment. Several
      population pharmacokinetics models (POPPK) allowing AUC determination have been
      developed, but only a few are actually used in routine practice for dose
      individualization. These POPPK models can also be used to perform Monte Carlo
      simulations that help to establish different dosing rules or to anticipate the
      pharmacokinetics of tacrolimus in particular populations, without conducting
      clinical trials. Various available applications of POPPK models to assist the
      prescriber in choosing the best tacrolimus dose are discussed in this paper as
      well as the difficulties in introducing them into routine therapeutic drug
      monitoring.

PMID- 29452288
TI  - Repetitive TLR3 activation in the lung induces skeletal muscle adaptations and
      cachexia.
AB  - Due to immunosenescence, older adults are particularly susceptible to lung-based
      viral infections, with increased severity of symptoms in those with underlying
      chronic lung disease. Repeated respiratory viral infections produce lung
      maladaptations, accelerating pulmonary dysfunction. Toll like 3 receptor (TLR3)
      is a membrane protein that senses exogenous double-stranded RNA to activate the
      innate immune response to a viral infection. Polyinosinic-polycytidylic acid
      [poly(I:C)] mimics double stranded RNA and has been shown to activate TLR3.
      Utilizing an established mouse viral exacerbation model produced by repetitive
      intranasal poly(I:C) administration, we sought to determine whether repetitive
      poly(I:C) treatment induced negative muscle adaptations (i.e. atrophy, weakness,
      and loss of function). We determined skeletal muscle morphological properties
      (e.g. fiber-type, fiber cross-sectional area, muscle wet mass, etc.) from a
      treated group ((poly(I:C), n = 9) and a sham-treated control group (PBS, n = 9);
      age approximately 5 months. In a subset (n = 4 for both groups), we determined in
      vivo physical function (using grip test for strength, rotarod for overall motor
      function, and treadmill for endurance) and muscle contractile properties with in
      vitro physiology (in the EDL, soleus and diaphragm). Our findings demonstrate
      that poly(I:C)-treated mice exhibit both muscle morphological and functional
      deficits. Changes of note when comparing poly(I:C)-treated mice to PBS-treated
      controls include reductions in fiber cross-sectional area (-27% gastrocnemius, 
      25% soleus, -16% diaphragm), contractile dysfunction (soleus peak tetanic force, 
      26%), muscle mass (gastrocnemius -19%, soleus -23%), physical function (grip test
      -34%), body mass (-20%), and altered oxidative capacity (140% increase in
      succinate dehydrogenase activity in the diaphragm, but 66% lower in the
      gastrocnemius). Our data is supportive of a new model of cachexia/sarcopenia that
      has potential for future research into the mechanisms underlying muscle wasting.

PMID- 29452292
TI  - Prevalence, risk factors and genetic characterization of Toxoplasma gondii in
      sick pigs and stray cats in Jiangsu Province, eastern China.
AB  - Toxoplasma gondii is an obligate intracellular parasitic protozoan with a
      worldwide distribution. The parasites in edible tissues of pigs and oocysts from
      cats are the major sources of T. gondii infection in humans. However, there are
      no data from sick pigs in veterinary clinics or from stray cats in Jiangsu
      Province, eastern China. In total, biological samples from 141 sick pigs and 64
      stray cats were collected from this region. The rate of T. gondii infection in
      sick pigs was 46.81% using a polymerase chain reaction (PCR), and the overall
      prevalence of toxoplasmosis in stray cats was 34.38% by PCR and an enzyme-linked
      immunosorbent assay (ELISA). T. gondii was significantly more prevalent in lungs
      and heart than in liver and spleen (P < 0.05). Age and geographic region were
      considered to be the main risk factors associated with T. gondii infection in
      these pigs. The DNA samples from 17 sick pigs and seven stray cats, were
      successfully genotyped by multilocus PCR-restriction fragment length polymorphism
      (PCR-RFLP) with 10 genetic markers [SAG1, SAG2 (5'-3'SAG2, alt. SAG2), SAG3,
      GRA6, PK1, c22-8, c29-2, BTUB, L358 and Apico]. Six distinct genotypes were
      found, which were designated ToxoDB PCR-RFLP genotypes #9 (Chinese I), #10 (Type
      I), #213, and #89, and New 1 and New 2. Chinese I is the most prevalent T. gondii
      genotype in this region. The two new genotypes (designated New 1 and New 2) are
      reported and the ToxoDB PCR-RFLP genotype #89 is found for the first time in
      China. Such information will be useful for the prevention, diagnosis and
      treatment of porcine toxoplasmosis in Jiangsu Province, eastern China.

PMID- 29452293
TI  - Genetic diversity and functional analysis of oipA gene in association with other
      virulence factors among Helicobacter pylori isolates from Iranian patients with
      different gastric diseases.
AB  - Helicobacter pylori (H. pylori) is one of the most genetically diverse bacterial
      pathogens that persistently colonizes the human gastric epithelium. This
      remarkable genomic plasticity may act as a driving force for successful
      adaptation and persistence of the bacteria in the harsh gastric environment.
      Outer inflammatory protein A (OipA) encoded by oipA gene (HP0638/hopH) is a
      member of the outer membrane proteins (OMPs) of H. pylori involved in induction
      of IL-8 secretion and is associated with development of peptic ulcer and gastric
      cancer. Expression of OipA is regulated by phase variation within a CT
      dinucleotide repeat motif of the oipA gene. In this study we carried out direct
      DNA sequence analysis of 53 amplified fragments to investigate the oipA "On/Off"
      status among Iranian H. pylori isolates from patients with various gastric
      diseases. The prevalence of cagL, cagA, EPIYA motifs, vacA alleles, babA2 and
      sabA genotypes as well as cagPAI integrity of the isolates were determined by
      PCR. Our results demonstrated a high prevalence of strains with functional oipA
      status (79%) and significant associations were found between functional oipA and
      cagA (P = 0.027) and vacA s1m1 (P = 0.022) genotypes. The vacA s1m2 genotype was
      also found to be statistically associated with PUD (P = 0.0001). Interestingly,
      we showed that H. pylori strains with intact cagPAI co-expressed oipA gene in a
      significant synergistic relationship (P < 0.01). However, no significant
      association was observed between the functional oipA status and clinical outcomes
      (P > 0.05). In conclusion, our findings denotes great diversity in the number and
      pattern of CT dinucleotide repeats of oipA among Iranian H. pylori strains. The
      synergistic link between functional oipA and other important virulence factors is
      proposed to be critical in the pathogenesis of H. pylori, which needs further
      studies with a larger number of samples.

PMID- 29452294
TI  - Vitamin D pathway genetic variants are able to influence sofosbuvir and its main
      metabolite pharmacokinetics in HCV mono-infected patients.
AB  - Vitamin D levels and genetic variants were associated with drug outcome/toxicity
      and concentrations. The plasma exposure of GS-331007, the main sofosbuvir
      metabolite, has been related to SVR. We evaluated the impact of polymorphisms in
      genes (CYP27B1, CYP24A1, VDBP and VDR) related to vitamin D pathway on sofosbuvir
      and GS-331007 plasma levels in HCV mono-infected patients at one month of
      treatment. Polymorphisms were investigated through real-time PCR; drug plasma
      quantification was performed through a UHPLC-MS/MS method. GS-331007 levels were
      associated with CYP24A1rs2248359 and VDRCdx2 variants in all the analyzed
      patients and linear regression analysis showed that sex, body mass index, HCV
      genotype, baseline estimated glomerular filtration rate, VDRCdx2AG/GG and CYP27B1
      1260TT genotypes significantly predict concentrations. We performed sub-analyses
      considering the HCV genotype and the concomitant drug, identifying polymorphisms
      associated with GS-331007 concentrations. This is the first study focusing on
      vitamin D pathway gene variants and DAAs concentrations, but further studies are
      required.

PMID- 29452295
TI  - What Types of Treatment Are Provided for Patients With Carpal Tunnel Syndrome? A
      Retrospective Analysis of Commercial Insurance.
AB  - BACKGROUND: Treatment of carpal tunnel syndrome (CTS) in commercially insured
      patients across the spectrum of provider types rarely has been described.
      OBJECTIVE: To describe patterns of types of treatment for patients with CTS using
      a large commercial insurance database. DESIGN: Retrospective cohort descriptive
      study. SETTING: Administrative health data from the Clinformatics Data Mart
      (OptumInsight, Eden Prairie, MN). PATIENTS: Adults with a primary diagnosis of
      CTS seen from between January 2010 to December 2012 who had a total of 48 months
      of continuous data (12 months before diagnosis and 36 months after diagnosis) (n
      = 24,931). OUTCOMES: Frequency of types of treatment (heat, manual therapy,
      positioning, steroids, stretching, surgery) by number of treatments, number of
      visits, provider type, and characteristics. RESULTS: Fifty-four percent of
      patients received no reported treatment, and 50.4% had no additional visits.
      Surgery (42.5%) and positioning (39.8%) were the most frequent single treatments.
      Patients who were seen by orthopedist for their first visit more frequently
      received some treatment (75.1%) and at least 1 additional visit (74.1%) compared
      with those seen by general practitioners (59.5%, 57.5%, respectively) or other
      providers (65.4%, 68.4, respectively). Orthopedists more frequently prescribed
      positioning devices (26.8%) and surgery (36.8%) than general practitioners
      (18.8%, 14.1%, respectively) or other providers (15.7%, 19.7%, respectively).
      Older adults more frequently had CTS surgery, as did people who lived in the
      Midwest. Overall, only 24% of patients with CTS had surgery. CONCLUSIONS: For
      more than one-half of patients with CTS no treatment was provided after an
      initial visit. Surgery rates were much lower than what has previously been
      reported in the literature. Generally, patients with CTS receive treatments that
      are supported by current treatment guidelines. LEVEL OF EVIDENCE: NA.

PMID- 29452296
TI  - Development and Persistence of Suspected Neuropathic Pain After Total Knee
      Arthroplasty in Individuals With Osteoarthritis.
AB  - BACKGROUND: Despite the effectiveness of total knee arthroplasty (TKA) for
      osteoarthritis (OA), up to 20% will report knee pain 1 year after surgery. One
      possible reason is the development of neuropathic pain before or after TKA.
      OBJECTIVE: To longitudinally describe suspected neuropathic pain in patients pre-
      and post-TKA and to explore relations between pre-TKA suspected neuropathic pain
      and post-TKA outcomes. DESIGN: Prospective observational study. SETTING:
      Participants were recruited from orthopedic surgery clinics prior to inpatient
      elective primary TKA. PARTICIPANTS: Convenience sample of 135 patients were
      assessed for eligibility; 99 were enrolled and 74 completed the 6-month follow
      up. METHODS: Participants completed the Self-Leeds Assessment of Neuropathic
      Symptoms and Signs (S-LANSS) and outcome measures at baseline (pre-TKA) and 1 and
      6 months post-TKA by postal survey. Demographic variables included age, gender,
      and comorbidities. Descriptive statistics were calculated for the presence of
      suspected neuropathic pain at each assessment and course of outcomes for various
      suspected neuropathic pain trajectories. Further, t-tests were used to compare
      outcomes between those with and without suspected neuropathic pain at each
      assessment. Multiple linear regressions assessed the relationship between
      baseline suspected neuropathic pain and 6-month outcomes. MAIN OUTCOME
      MEASUREMENTS: Intermittent and Constant Osteoarthritis Pain (ICOAP), Pain
      Catastrophizing Scale (PCS), and the Patient Health Questionnaire (PHQ-9) for
      depression. RESULTS: Suspected neuropathic pain was present in 35.5% of pre-TKA
      patients, 39.0% at 1 month, and 23.6% at 6 months post-TKA. Those with suspected
      neuropathic pain had higher scores for ICOAP total pain (P = .05), pain
      catastrophizing (P < .01), and depression (P < .01) at each assessment. After
      adjusting for potential confounding, pre-TKA suspected neuropathic pain did not
      predict ICOAP total pain or PHQ-9 depression scores at 6 months. CONCLUSIONS:
      Although 14% of individuals with knee OA had suspected neuropathic pain that
      persisted 6 months post-TKA and those with suspected neuropathic pain had higher
      levels of pain, catastrophizing, and depression, the clinical identification of
      neuropathic pain remains enigmatic. Preoperative suspected neuropathic pain, as
      measured by S-LANSS, may have limited prognostic value for post-TKA outcomes.
      LEVEL OF EVIDENCE: II.

PMID- 29452297
TI  - Lumbar Intraspinal Spindle Cell Rhabdomyosarcoma as a Rare Cause of Spinal
      Stenosis: A Case Report.
AB  - : Rhabdomyosarcoma (RMS) represents the most common sarcoma in childhood yet is
      extremely rare in adults, with only a handful of cases reported. Here we present
      a case of intraspinal spindle cell RMS in an adult who presented as a typical
      case of spinal stenosis. To our knowledge, this is the first reported case of
      lumbar intraspinal spindle cell RMS in an adult patient. Furthermore, RMS
      phenotypically presents more aggressively in adults compared with children. LEVEL
      OF EVIDENCE: V.

PMID- 29452298
TI  - Treatment and outcomes in patients with IgG4-related disease using the IgG4
      responder index.
AB  - BACKGROUND: IgG4-related disease (IgG4-RD) is an autoimmune disease triggering an
      inflammatory cascade that leads to fibrosis. Outcome measures are limited and
      treatment options remain underexplored. OBJECTIVES: To assess the variation of
      the IgG4 responder index (IgG4-RI) in a cohort of IgG4-RD patients and to explore
      their treatments and outcomes. METHODS: We studied the clinical phenotype,
      severity of the disease and response to treatment in an ambispective multicenter
      cohort study including 14 different hospitals in Spain. All patients met the 2012
      international consensus on pathology criteria for diagnosis. RESULTS: Sixty-eight
      patients were included, with a mean age of 53.4 years and predominance of male
      sex. The most commonly involved tissues were: retroperitoneum (33%), orbital
      pseudotumor (28%) and maxillary and paranasal sinuses (24%). IgG4-RI values were
      higher in patients with multiorgan disease and before treatment. After being
      treated, IgG4-RI values were lower, in accordance with the high rates of
      treatment response. Most patients received: glucocorticoids (GC), surgery,
      azathioprine (AZA), mofetil mycophenolate or rituximab. GC alone, GC plus surgery
      and GC plus AZA were given in the most of the IgG4-RD disease activity episodes.
      All treatments had high response rates but relapses and flares were common.
      CONCLUSIONS: IgG4-RI is a promising outcome measure in IgG4-RD, but still in
      development. Treatment algorithms are ill defined. GC and rituximab are the drugs
      with more evidence available. Disease modifying anti-rheumatic drugs may have a
      role in IgG4-RD and warrant more prospective studies.

PMID- 29452299
TI  - Non-celiac gluten intolerance in patients with scleroderma.

PMID- 29452300
TI  - Therapeutic strategy for rheumatoid arthritis patients who have achieved
      remission.
AB  - Once remission or low disease activity (LDA) is attained in established
      rheumatoid arthritis (RA) patients, attempting disease-modifying anti-rheumatic
      drug (DMARD) tapering appears to be a viable option to avoid patient
      overtreatment. Potential benefits include reduction in the treatment burden and
      the risk of adverse events, although the latter has not been demonstrated
      convincingly. The feasibility of DMARD discontinuation has been tested in
      numerous studies or trials. All have revealed a high risk of relapse, ranging
      from 56%-87% at one year. Although remission/LDA can usually be re-established by
      re-initiation of the previous treatment, the associated risk appears to be more
      harmful than beneficial. DMARD tapering, either by dose reduction or by injection
      spacing, is conceptually more acceptable and two superiority randomized
      controlled trials (RCTs) comparing half-dose etanercept to full-dose continuation
      demonstrated no significant difference at one year. By contrast, two equivalence
      RCTs that tested disease activity-guided dose optimization by progressive
      etanercept and adalimumab injection spacing versus continuation revealed an
      increased risk of acute flare. Interestingly, one of these also demonstrated the
      equivalence of increasing injection spacing and standard of care in terms of
      recurrent flare and overall disease activity over the 18-month follow-up period.
      The risk of structural damage progression was minimal or null. Reintroduction of
      DMARD at the previous dose was associated with remission being achieved in the
      majority of patients who flared. Tapering strategies that adhere to the Tight
      Control and Treat-to-Target principles appear to be suitable options for RA
      patients who have achieved sustained remission or low disease activity.

PMID- 29452301
TI  - Failure of conventional treatment and losartan in Camurati-Engelmann disease: A
      case report.

PMID- 29452302
TI  - Switching of biologics in RA patients who do not respond to the first biologic.

PMID- 29452303
TI  - Effect of biologics on fatigue in psoriatic arthritis: A systematic literature
      review with meta-analysis.
AB  - OBJECTIVES: Fatigue is a significant issue in psoriatic arthritis. The objective
      was to assess the effect of biological disease modifying antirheumatic drugs and
      apremilast on fatigue in psoriatic arthritis randomised controlled trials and to
      compare this effect with the effect in the same trials, on pain, through a
      systematic literature review and meta-analysis. METHODS: A systematic literature
      review was performed up to January 2017 in PubMed, Embase and Cochrane databases.
      All randomized controlled trials in psoriatic arthritis of biological disease
      modifying antirheumatic drugs or apremilast, assessing fatigue (whatever the
      score used), were included. Data were collected by 2 assessors regarding levels
      of fatigue and pain at baseline and at the time point closest to 24 weeks after
      the treatment introduction. Pooled standardized mean differences were calculated
      using RevMan. RESULTS: After screening 295 publications, 7 randomised controlled
      trials were analysed: they pertained to adalimumab (n=2), certolizumab pegol
      (n=1), secukinumab (n=2), ustekinumab (n=1) and apremilast (n=1), compared to
      placebo. The studies included 2341 patients: weighted mean+/-standard deviation
      age: 48.6+/-1.3years, disease duration: 7.7+/-1.6years, 51.6% were females.
      Fatigue levels were high at baseline (Functional Assessment of Chronic Illness
      Therapy score: 28.7+/-2.4). The pooled standardized mean difference was, for
      fatigue -0.44 (95% confidence interval: -0.54, -0.35) and for pain, -0.62 (-0.73,
      -0.52). CONCLUSIONS: Biological disease modifying antirheumatic drugs and
      apremilast had a small effect on fatigue at 24 weeks in psoriatic arthritis
      randomized controlled trials and a higher effect on pain. These results are
      important to take into account in shared decision-making.

PMID- 29452304
TI  - The chondrocyte channelome: A narrative review.
AB  - Chondrocytes are the main cells in the extracellular matrix (ECM) of articular
      cartilage and possess a highly differentiated phenotype that is the hallmark of
      the unique physiological functions of this specialised load-bearing connective
      tissue. The plasma membrane of articular chondrocytes contains a rich and diverse
      complement of membrane proteins, known as the membranome, which defines the cell
      surface phenotype of the cells. The membranome is a key target of pharmacological
      agents and is important for chondrocyte function. It includes channels,
      transporters, enzymes, receptors, and anchors for intracellular, cytoskeletal and
      ECM proteins and other macromolecular complexes. The chondrocyte channelome is a
      sub-compartment of the membranome and includes a complete set of ion channels and
      porins expressed in these cells. Many of these are multi-functional proteins with
      "moonlighting" roles, serving as channels, receptors and signalling components of
      larger molecular assemblies. The aim of this review is to summarise our current
      knowledge of the fundamental aspects of the chondrocyte channelome, discuss its
      relevance to cartilage biology and highlight its possible role in the
      pathogenesis of osteoarthritis (OA). Excessive and inappropriate mechanical
      loads, an inflammatory micro-environment, alternative splicing of channel
      components or accumulation of basic calcium phosphate crystals can result in an
      altered chondrocyte channelome impairing its function. Alterations in Ca2+
      signalling may lead to defective synthesis of ECM macromolecules and aggravated
      catabolic responses in chondrocytes, which is an important and relatively
      unexplored aspect of the complex and poorly understood mechanism of OA
      development.

PMID- 29452305
TI  - Spontaneous epidural hematoma of the cervical spine after caesarean section.

PMID- 29452306
TI  - Boundaries between familial Mediterranean fever and juvenile spondyloarthritis:
      Analysis of three French retrospective cohorts.
AB  - OBJECTIVES: Children with Familial Mediterranean fever may suffer from
      musculoskeletal involvement, somewhat difficult to distinguish from juvenile
      spondyloarthritis. The association of these two diseases has been scarcely
      reported in children. Objective of this work was to define the association of
      familial Mediterranean fever and juvenile spondyloarthritis in France. METHODS:
      Three cohorts of children with familial Mediterranean fever, juvenile
      spondyloarthritis, familial Mediterranean fever related juvenile
      spondyloarthritis, were retrospectively identified in the French reference center
      of auto-inflammatory diseases. Familial Mediterranean fever was defined according
      to Tel-Hashomer or Turkish pediatric criteria with at least one exon-10 MEFV-gene
      mutation. Juvenile spondyloarthritis was defined according to ILAR criteria.
      Patients with familial Mediterranean fever or juvenile spondyloarthritis were
      respectively compared to familial Mediterranean fever related juvenile
      spondyloarthritis patients. RESULTS: Sixteen children were identified as having
      familial Mediterranean fever related juvenile spondyloarthritis. The male/female
      ratio was 0.6, with median age at spondyloarthritis onset of 7.5years (3
      16years). All carried at least one M694V variant in MEFV gene; 16.7% were HLA-B27
      carriers. Compared to 83 familial Mediterranean fever patients, familial
      Mediterranean fever related juvenile spondyloarthritis patients had less
      frequently fever (P<0.01) and more frequently arthritis (P<0.05), enthesitis
      (P<0.001), inflammatory back pain (P<0.001), inadequate response to colchicine
      (P<0.05). Compared to 20 juvenile spondyloarthritis patients, familial
      Mediterranean fever related juvenile spondyloarthritis patients less often
      received non-steroidal anti-inflammatory drugs (P<0.01) and anti-tumor necrosis
      factor drugs (P<0.001). CONCLUSIONS: Familial Mediterranean fever may be
      associated with typical pattern of juvenile spondyloarthritis. These patients,
      with less response to colchicine, should be diagnosed earlier and treated as for
      jSpA.

PMID- 29452307
TI  - Impact of metabolic syndrome on clinical severity and long-term prognosis in
      patients with myocardial infarction with ST-segment elevation.
AB  - AIMS: The aim of this study is to evaluate the impact of metabolic syndrome
      (MetS) on clinical severity and long-term prognosis in patients with myocardial
      infarction with ST-segment elevation (STEMI). METHODS: We examined 507 patients
      with STEMI, who were admitted for primary percutaneous coronary intervention
      classified according to the presence of MetS using American Heart Association and
      the National Heart, Lung, and Blood Institute definition. After applying these
      criteria, the patients were categorized into groups as patients with MetS and
      without MetS. We compared baseline characteristics, clinical findings, and
      outcomes between these groups. During the 48-month follow-up, we collected data
      about major adverse cardiac events (MACE) and mortality. RESULTS: The MetS group
      comprised 217 patients with MetS (mean age = 60.71 +/- 11.52 years; 59 females),
      while the control group comprised 290 subjects (mean age = 57.50 +/- 10.95 years;
      54 females). The patients with and without MetS had similar parameters of
      clinical severity of STEMI but differed in severe coronary artery disease. During
      the follow-up period, a significantly higher percentage of myocardial infarction
      (6.91% vs 2.06%) and new revascularization (16.59% vs 8.97%) was recorded in the
      MetS group. On multivariate analysis, MetS was independently associated with MACE
      (HR = 1.834, 95% CI = 1.162-2.896, p = 0.009) but not with mortality (HR = 1.603,
      95% CI = 0.864-2.973, p = 0.134). Among cardiovascular events that compose MACE,
      MetS was associated with new revascularization (HR = 2.204, 95% CI = 1.273-3.815,
      p=0.005). CONCLUSION: The presence of MetS in patients with STEMI is an
      independent risk factor for MACE, and this syndrome is strongly associated with
      new revascularization.

PMID- 29452308
TI  - A case of pheochromocytoma crisis simulating acute coronary syndrome and multiple
      organ dysfunction syndrome.

PMID- 29452309
TI  - Echocardiography for the management of patients with biventricular pacing:
      Possible roles in cardiac resynchronization therapy implementation.
AB  - Cardiac resynchronization therapy (CRT) is an established therapeutic option for
      the subset of patients with heart failure (HF), reduced ejection fraction (EF),
      and dyssynchrony evidenced by electrocardiography. Benefit from CRT has been
      proven in many clinical trials, yet a sizeable proportion of these patients with
      wide QRS do not respond to this intervention, despite the updated practice
      guidelines. Several echocardiographic indices, targeting mechanical rather than
      electrical dyssynchrony, have been suggested to address this issue, but research
      so far has not succeeded in providing a single and simple measurement with
      adequate sensitivity and specificity for identification of responders. While
      there is still ongoing research in this field, echocardiography proves helpful in
      other aspects of CRT implementation, such as site selection for left ventricular
      (LV) lead pacing and optimization of pacing parameters during follow-up visits.

PMID- 29452310
TI  - Serial long-term follow-up of a medically managed aortic prosthetic valve
      thrombosis.

PMID- 29452311
TI  - Phylogenetic relationships and cryptic species diversity in the Brazilian egg
      brooding tree frog, genus Fritziana Mello-Leitao 1937 (Anura: Hemiphractidae).
AB  - The genus Fritziana (Anura: Hemiphractidae) comprises six described species (F.
      goeldii, F. ohausi, F. fissilis, F. ulei, F. tonimi, and F. izecksohni) that are
      endemic to the Brazilian Atlantic Forest. Although the genus has been the subject
      of studies dealing with its taxonomy, phylogeny, and systematics, there is
      considerable evidence for cryptic diversity hidden among the species. The present
      study aims to understand the genetic diversity and phylogenetic relationships
      among the species of Fritziana, as well as the relationships among populations
      within species. We analyzed 107 individuals throughout the distribution of the
      genus using three mitochondrial gene fragments (12S, 16S, and COI) and two
      nuclear genes (RAG1 and SLC8A3). Our data indicated that the species diversity in
      the genus Fritziana is underestimated by the existence of at least three
      candidate species hidden amongst the group of species with a closed dorsal pouch
      (i.e. F. fissilis and F. ulei). We also found four species presenting
      geographical population structures and high genetic diversity, and thus require
      further investigations. In addition, we found that two candidate species show a
      new arrangement for the tRNA-Phe gene, unique in Anura so far. Based on our
      results, we suggest that the conservation status of the species, as well as the
      species diversity in the genus Fritziana, needs to be reviewed.

PMID- 29452312
TI  - Effects of Higher Versus Lower Threat Contexts on Pain-Related Visual Attention
      Biases: An Eye-Tracking Study of Chronic Pain.
AB  - : In this research, we examined effects of higher versus lower threat contexts on
      attention biases in more and less pain-fearful chronic pain subgroups via eye
      tracking methodology. Within a mixed chronic pain sample (69 women, 29 men),
      biases in orienting and maintenance of visual attention were assessed during the
      standardized image pair presentation phase (2,000 ms) of a modified visual dot
      probe task featuring painful-neutral (P-N) image pairs (lower threat context) and
      a parallel task in which these P-N pairs cued potential pain (higher threat
      context). Across both tasks, participants more often oriented toward, gazed
      longer at, and made more unique fixations upon pain images during P-N pair
      presentations. Although trait-based fear of pain was not related to any gaze bias
      index in either task, between task analyses indicated the sample reported more
      state fear, directed their initial gaze less often, and displayed longer overall
      gaze durations toward pain images in the higher threat context in which P-N
      trials signaled potential pain. Results supported the threat interpretation model
      premise that persons with chronic pain have difficulty disengaging from
      moderately threatening visual painful cues. PERSPECTIVE: Through integrating dot
      probe and impending pain task paradigms, we assessed effects of lower versus
      higher threat contexts on visual attention biases of persons with chronic pain
      via eye tracking. Under higher threat conditions featuring possible pain, state
      fear levels were elevated and maintenance of attention on painful depictions was
      more prolonged.

PMID- 29452313
TI  - Does the Iliac Wing Influence L5 Pedicle Screw Fixation?
AB  - OBJECTIVE: To explore whether the iliac wing influences L5 pedicle screw (PS)
      fixation and to propose methods to reduce such influence. METHODS: A total of 100
      computed tomography scans (from 50 male and 50 female patients) of the lower
      lumbar region and pelvis were obtained and 3-dimensionally reconstructed.
      Cylinders with 6.5-mm diameters were drawn to simulate the different trajectories
      of L5 PS. The maximum lengths and lateral angles of trajectories, and the
      vertical distances from the inner edge of the iliac wing to these trajectories,
      were measured. RESULTS: The maximum lengths and lateral angles differed
      significantly among trajectories; the maximum length, but not the lateral angle,
      differed significantly between male and female subjects. The influence of the
      iliac wing was more significant in male than in female subjects. The iliac wing
      had a greater effect on screws implanted along the pedicle axis than on screws
      for which the trajectories commenced at Du's entry point and passed through the
      center of the pedicle. CONCLUSIONS: This study elucidates the influence of the
      iliac wing on L5 PS fixation. Careful attention is required when implanting PSs,
      especially in male patients. The combined use of Du's technique and a
      percutaneous method for PS implantation effectively reduces the influence of the
      iliac wing. To minimize the complications of PS fixation further, preoperative
      simulation of fixation for each patient is very important.

PMID- 29452314
TI  - Movement Disorders and Deep Brain Stimulation in the Middle East.
AB  - BACKGROUND: Deep brain stimulation (DBS) is a well-established neuromodulation
      therapy for advanced Parkinson disease, essential tremor and dystonia. In as much
      as this therapy is being developed in the Middle East, a better understanding of
      the incidence and prevalence of movement disorders, health care, and social
      framework is required for the region. METHODS: We reviewed current literature on
      the incidence and prevalence of various movement disorders in the Middle East
      amenable to DBS surgery. We also assessed recent efforts to develop DBS in the
      region. RESULTS: Available data on incidence and prevalence of movement disorders
      in the Middle East are old, inconclusive, and conflicting. We identify key areas
      such as cultural background, availability of accessible information, training,
      infrastructure, and public support groups in the region that may pose challenges.
      CONCLUSIONS: The Middle East is projected to be a growing market for
      neuromodulation. The available data on incidence and prevalence of movement
      disorders is from studies that were small, partial, and old, with inconsistent
      results, highlighting the need for newer, better-designed, and larger studies.
      DBS in the Middle East will need assessment of incidence and prevalence of
      movement disorders, existing challenges to its application, and focused efforts
      on key opportunities to foster development of DBS for this underserved region.
      This article is an attempt to identify and explore these challenges and propose
      solutions in anticipation.

PMID- 29452315
TI  - Technical Aspects of Awake Craniotomy with Mapping for Brain Tumors in a Limited
      Resource Setting.
AB  - BACKGROUND: Brain tumor surgery near or within eloquent regions is increasingly
      common and is associated with a high risk of neurologic injury. Awake craniotomy
      with mapping has been shown to be a valid method to preserve neurologic function
      and increase the extent of resection. However, the technique used varies greatly
      among centers. Most count on professionals such as neuropsychologists, speech
      therapists, neurophysiologists, or neurologists to help in intraoperative patient
      evaluation. We describe our technique with the sole participation of
      neurosurgeons and anesthesiologists. METHODS: A retrospective review of 19
      patients who underwent awake craniotomies for brain tumors between January 2013
      and February 2017 at a tertiary university hospital was performed. We sought to
      identify and describe the most critical stages involved in this surgery as well
      as show the complications associated with our technique. RESULTS: Preoperative
      preparation, positioning, anesthesia, brain mapping, resection, and management of
      seizures and pain were stages deemed relevant to the accomplishment of an awake
      craniotomy. Sixteen percent of the patients developed new postoperative deficit.
      Seizures occurred in 24%. None led to awake craniotomy failure. CONCLUSIONS: We
      provide a thorough description of the technique used in awake craniotomies with
      mapping used in our institution, where the intraoperative patient evaluation is
      carried out solely by neurosurgeons and anesthesiologists. The absence of other
      specialized personnel and equipment does not necessarily preclude successful
      mapping during awake craniotomy. We hope to provide helpful information for those
      who wish to offer function-guided tumor resection in their own centers.

PMID- 29452316
TI  - Endoscopic Neurosurgery: Surgeon Versus Machine.

PMID- 29452317
TI  - Minimally Invasive Alternative Approaches to Pterional Craniotomy: A Systematic
      Review of the Literature.
AB  - OBJECTIVE: Minimally invasive alternatives to the pterional craniotomy include
      the minipterional and the supraorbital craniotomy (SOC). The latter is performed
      via either an eyebrow or an eyelid skin incision. The purpose of this systematic
      review was to analyze the type and the incidence of approach-related
      complications of these so-called "keyhole craniotomies". METHODS: We review
      pertinent articles retrieved by search in the PubMed/Medline database. Inclusion
      criteria were all full-text articles, abstracts, and posters in English, up to
      2016, reporting clinical results. RESULTS: A total of 105 articles containing
      data on 5837 surgeries performed via a minipterional or either of the 2 variants
      of the SOC met the eligibility criteria. Pain on mastication was the most
      commonly reported approach-related complication of the minipterional approach,
      and occurred in 7.5% of cases. Temporary palsy of the frontal branch of the
      facial nerve and temporary supraorbital hypesthesia were associated with the SOC
      eyebrow variant, and occurred in 6.5%, respectively in 3.6% of cases. Transient
      postoperative periorbital edema and transient ophthalmoparesis occurred in 36.8%
      and 17.4% of cases, respectively, when the SOC was performed via an eyelid skin
      incision. The risk of occurrence of the latter 2 complications was related to the
      removal of the orbital rim, which is an obligatory part of the SOC approach
      through the eyelid but optional with the SOC eyebrow variant. CONCLUSIONS: Each
      of the 3 keyhole approaches has a specific set and incidence of approach-related
      complications. It is essential to be aware of these complications to make the
      safest individual choice.

PMID- 29452318
TI  - Bone Metabolic Markers in the Clinical Assessment of Patients with Superior
      Semicircular Canal Dehiscence.
AB  - BACKGROUND: Superior semicircular canal dehiscence (SSCD) is a bony defect in the
      osseous shell of the petrous temporal bone. The pathophysiological association
      between osteoporosis and SSCD remains poorly understood. We investigated the
      relationship between bone metabolic markers and symptoms in patients with SSCD.
      METHODS: We collected patient demographics and clinical parameters for adult
      patients diagnosed with SSCD on high-resolution computed tomography scans. We
      used point-biserial correlation analysis to investigate the relationship between
      bone metabolic markers and symptoms in patients with SSCD. We compared clinical
      symptoms before and after surgical repair of SSCD through a middle fossa
      craniotomy using McNemar's test for paired comparisons of binary measures.
      RESULTS: We included a total of 99 patients (64 females and 35 males; average age
      52 years; 118 surgeries). The level of serum calcium correlated with the need for
      a second surgery (rpb = -0.35, P = 0.001). Postoperative calcium supplementation
      negatively correlated with improvement in dizziness (rpb = -0.36, P = 0.01). The
      level of 25-hydroxyvitamin D correlated with preoperative hyperacusis (rpb = 
      0.98, P = 0.02) and postoperative autophony (rpb = 0.96, P = 0.04). Postoperative
      vitamin D supplementation positively correlated with hearing decline (rpb = 0.04,
      P = 0.04) The level of thyroid stimulating hormone correlated with preoperative
      autophony, amplification, and tinnitus (rpb = -0.71, rpb = -0.75, rpb = -0.70,
      all P < 0.001). CONCLUSIONS: Bone metabolic markers could be important in the
      clinical assessment of SSCD patients and could be potential targets for symptom
      management.

PMID- 29452319
TI  - "White Cord Syndrome" of Acute Hemiparesis After Posterior Cervical Decompression
      and Fusion for Chronic Cervical Stenosis.
AB  - BACKGROUND: "White cord syndrome" is a very rare condition thought to be due to
      acute reperfusion of chronically ischemic areas of the spinal cord. Its hallmark
      is the presence of intramedullary hyperintense signal on T2-weighted magnetic
      resonance imaging sequences in a patient with unexplained neurologic deficits
      following spinal cord decompression surgery. The syndrome is rare and has been
      reported previously in 2 patients following anterior cervical decompression and
      fusion. We report an additional case of this complication. CASE DESCRIPTION: A 68
      year-old man developed acute left-sided hemiparesis after posterior cervical
      decompression and fusion for cervical spondylotic myelopathy. The patient
      improved with high-dose steroid therapy. CONCLUSIONS: The rare white cord
      syndrome following either anterior cervical decompression and fusion or posterior
      cervical decompression and fusion may be due to ischemic-reperfusion injury
      sustained by chronically compressed parts of the spinal cord. In previous
      reports, patients have improved following steroid therapy and acute
      rehabilitation.

PMID- 29452320
TI  - The Risk of Traumatic Brain Injury Occurring Among Patients with Parkinson
      Disease: A 14-Year Population-Based Study.
AB  - BACKGROUND: Previous studies have implicated traumatic brain injury (TBI) as a
      risk factor for Parkinson disease (PD). However, the incidence risk of new-onset
      TBI among patients with PD is not well established. This study investigated the
      contribution of PD to new-onset TBI associations. METHODS: The study selected
      6076 patients with PD and using 1:2 propensity score matching 12,152 general
      population cohorts in a longitudinal population database in Taiwan. The Cox
      proportional hazard regression model was used to estimate the hazard ratio of TBI
      adjusted with the potential confounding factors. RESULTS: The incidence of TBI in
      patients with PD (2.57%) and compared cohorts (1.81%) was significantly different
      (P = 0.0007). Patients with PD had a higher risk of TBI (hazard ratio, 1.63; 95%
      confidence interval, 1.32-2.01) compared with the general population. Patients
      with PD with TBI incidence had a higher Charlson Comorbidity Index than did the
      general population with TBI (P < 0.0001). Fall is the major cause of TBI in
      patients with PD. CONCLUSIONS: This study shows that patients with PD have a high
      risk of TBI, and the major cause of TBI in patients with PD is fall.

PMID- 29452321
TI  - Hypoplastic Straight Sinus with Persistent Falcine Sinus in Adult with Sinus
      Pericranii.
AB  - Open magnetic resonance imaging of a 45-year-old man with panic disorder showed a
      sinus pericranii (SP). Examination of the scalp revealed a discolored scalp mass,
      and magnetic resonance venography displayed a hypoplastic straight sinus with
      persistent falcine sinus. SP is a venous anomaly consisting of a transosseous
      vascular channel connecting an intracranial sinus with subgaleal veins. High
      venous pressure in the late embryonic stage, as with a hypoplastic straight
      sinus, has been hypothesized to predispose affected individuals to develop other
      venous anomalies (i.e., falcine sinus). Because there is no major venous outflow
      through this accessory SP in an asymptomatic adult, no intervention was
      recommended for our patient.

PMID- 29452322
TI  - End-Stage Liver Disease in Patients with Intracranial Hemorrhage Is Associated
      with Increased Mortality: A Cohort Study.
AB  - OBJECTIVE: To determine if end-stage liver disease (ESLD) in patients with
      intracranial hemorrhage (ICH) is associated with increased mortality. METHODS:
      This single-center, retrospective cohort study included 53 patients (33 in ESLD
      cohort and 20 in non-ESLD cohort) who received neurosurgical care between 2006
      and 2017. ESLD was defined clinically as severely impaired liver function and at
      least 1 major complication of liver failure. The primary outcome was mortality.
      RESULTS: Overall, in-hospital, and 30-day mortality rates were higher in the ESLD
      cohort versus the non-ESLD cohort (79 vs. 30%, 79 vs. 20%, and 64 vs. 25%, all P
      <= 0.01). We identified a significant difference in overall survival between ESLD
      and non-ESLD cohorts on Kaplan-Meier analysis (P = 0.004 with log-rank and
      Wilcoxon tests). Odds of overall, in-hospital, and 30-day mortality in the ESLD
      cohort were 8.67 (95% confidence interval [CI], 2.44-30.84), 14.86 (95% CI, 3.75
      58.90), and 5.25 (95% CI, 1.53-18.08). Other predictors of overall mortality
      included primary admission diagnosis of liver disease (odds ratio [OR] = 9.60;
      95% CI, 3.75-58.90), higher Child-Pugh (OR = 1.64; 95% CI, 2.66-34.67) and Model
      for End-Stage Liver Disease (OR = 1.12; 95% CI, 1.04-1.20) scores, lower Glasgow
      Coma Scale score (OR = 0.73; 95% CI, 0.61-0.88), ICH that developed in the
      hospital (OR = 4.11; 95% CI, 1.21-13.98), and intraparenchymal hemorrhage (OR =
      9.23; 95% CI, 1.72-49.56). CONCLUSIONS: ESLD in patients with ICH is associated
      with increased mortality.

PMID- 29452323
TI  - Burr Hole Surgery for Chronic Subdural Hematoma with Extensive Scalp Burn.
AB  - BACKGROUND: Neurosurgical intervention for a patient with an extensive scalp burn
      is rare, but it may be associated with a high risk of surgical site infection.
      CASE DESCRIPTION: An 80-year-old man had a severe and extensive scalp burn. A
      chronic subdural hematoma (CSDH) was observed on a computed tomographic view of
      the head, performed for the assessment of bacteremia during treatment in the
      intensive care unit. To evaluate whether the CSDH might underlie the patient's
      prolonged fever and sepsis, we urgently evacuated the hematoma using 1 burr hole.
      The surgery was uneventful. We made a skin incision through the deep burn wounds
      covering the right temporal muscle. We removed necrotic tissue from scalp burns
      continuously to avoid wound complications and intracranial infection.
      CONCLUSIONS: Temporal muscle with a constant blood supply served as an effective
      tissue for surgical wound closure. By use of this multidisciplinary approach, the
      CSDH resolved completely, and surgical wound complications were avoided.

PMID- 29452324
TI  - Microsurgical Clipping of Intracranial Aneurysms Assisted by Neurophysiological
      Monitoring, Microvascular Flow Probe, and ICG-VA: Outcomes and Intraoperative
      Data on a Multimodal Strategy.
AB  - OBJECTIVE: The aim of this study is to report data on a multimodal monitoring
      strategy based on the intraoperative use of neurophysiological monitoring,
      flowmetry by microflow probe, and intraoperative indocyanine green video
      angiography (ICG-VA) during microsurgical clipping of intracranial aneurysms.
      METHODS: This retrospective analysis was performed on 85 consecutive patients
      undergoing clipping of 96 intracranial aneurysms with the present monitoring
      strategy. Patient outcomes were evaluated by assessing rate of aneurysm exclusion
      and postoperative occurrence of ischemic injury. Intraoperative data for the
      strategy in addition to changes in each monitoring technique depending on
      aneurysm features were reported. RESULTS: Complete aneurysm exclusion was
      achieved in 98.9% of cases. Postoperative symptomatic ischemic injury was
      recorded in 2.08% aneurysms. Clip repositioning occurred in 40.6% of cases:
      because of motor evoked potential (MEP) decrease in 9.3%, flowmetry in 22.91%,
      and ICG-VA in 8.3% of treated aneurysms (1.05% after ICG injection, 7.4% after
      the squeezing maneuver). The role of each technique differed according to
      aneurysm features; flowmetry alterations occurred more frequently in distal than
      in proximal aneurysms (P = 0.0001) and in atherosclerotic aneurysms (P = 0.0001).
      MEP impairment occurred more often in proximal aneurysms (P < 0.05). ICG-VA
      disclosed remnant aneurysms mainly in atherosclerotic aneurysms (P < 0.05); only
      one false negative remnant neck was recorded with a negative predictive value of
      98.8%. CONCLUSIONS: Microsurgical clipping assisted by a multimodal monitoring
      strategy achieved a high rate of aneurysm exclusion with low morbidity in our
      series. Our data show that the 3 techniques used in our strategy were
      complementary and that a monitoring strategy can be tailored to aneurysm
      features.

PMID- 29452325
TI  - Treatment of Wide-Neck Bifurcation Aneurysm Using "WEB Device Waffle Cone
      Technique".
AB  - BACKGROUND: The endovascular treatment of wide-neck bifurcation aneurysms can be
      challenging and often requires the use of adjunctive techniques and devices.
      METHODS: We report our first experience of using a waffle-cone technique adapted
      to the Woven Endoluminal Bridge (WEB) device in a large-neck basilar tip
      aneurysm, suitable in cases where the use of Y stenting or other techniques is
      limited due to anatomic restrictions. RESULTS: The procedure was complete, and
      angiographic occlusion of the aneurysm was achieved 24 hours post treatment, as
      confirmed by digital subtraction angiography. No complications occurred.
      CONCLUSIONS: The case reported here was not suitable for Y stenting or deployment
      of the WEB device alone, due to the small caliber of both posterior cerebral
      arteries and their origin at the neck level. The main advantage of this technique
      is that both devices have a controlled detachment system and are fully
      independent. To our knowledge, this technique has not been reported previously
      and this modality of treatment has never been described in the literature.

PMID- 29452326
TI  - Awake Microvascular Decompression for Trigeminal Neuralgia: Concept and Initial
      Results.
AB  - BACKGROUND: In this initial series, we evaluated the use of microvascular
      decompression (MVD) under an awake anesthesia protocol ("awake" MVD) to assess
      whether intraoperative pain evaluation can identify and mitigate insufficient
      decompression of the trigeminal nerve, improving surgical outcomes, and possibly
      expand the indications of MVD in patients with comorbidities that would preclude
      the use of general endotracheal anesthesia (GEA). METHODS: An Institutional
      Review Board-approved prospective study of 10 consecutive adults who underwent
      MVD for trigeminal neuralgia (TN) was conducted. The primary outcome measure was
      postoperative TN pain quantified on the Barrow Neurological Institute (BNI) Pain
      Severity Scale. RESULTS: The median patient age was 65.5 years, with a
      female:male ratio of 6:4. All 10 patients tolerated the procedure well and did
      not require GEA intraoperatively or postoperatively. Nine patients had a
      successful surgical outcome (BNI score I, n = 5; BNI score II, n = 4). One
      patient did not have pain relief (BNI score IV). This same patient also developed
      a pseudomeningocele, which was the sole surgical complication observed in this
      series. One patient experienced recurrence of pain at 11 months, with BNI score
      increasing from I to II. The median duration of follow-up was 16.5 months. Two
      patients did not experienced resolution of evoked pain during intraoperative
      awake testing following decompression. Further intraoperative exploration
      revealed secondary offending vessels that were subsequently decompressed, leading
      to resolution of pain. CONCLUSIONS: Intraoperative awake testing for treatment
      efficacy may increase the success rate of MVD by rapidly identifying and
      mitigating insufficient cranial nerve V decompression.

PMID- 29452327
TI  - Effect and Feasibility of Endoscopic Surgery in Spontaneous Intracerebral
      Hemorrhage: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Spontaneous intracerebral hemorrhage remains a major cause of death
      and dependence. Endoscopic surgery (ES) is potential to improve outcomes, but a
      consensus on the superiority of ES has not been achieved. We conducted a
      systematic review to clarify the effect of ES in spontaneous intracerebral
      hemorrhage and compare it with other treatment options (craniotomy, conservation,
      and stereotactic aspiration [SA]). METHODS: We performed this review based on the
      Preferred Reporting Items for Systematic review and Meta-Analysis. The subgroup
      analyses were stratified by study type, location, hematoma volume, interval to
      treatment, follow-up time, and stereotactic frame assistance. RESULTS: A total of
      18 studies were included containing 1213 patients, most of whom harbored a
      hematoma greater than 50 mL. Compared with craniotomy and conservation, ES
      significantly reduced the mortality (P < 0.0001), poor outcomes (P < 0.00001),
      rebleeding (P = 0.0009), and pneumonia (P < 0.00001). In the subgroup analyses,
      late surgery (<48 hours) benefited more from ES than early surgery (<24 hours).
      The study location, hematoma volume, and stereotactic frame assistance
      insignificantly influenced the therapeutic effect of ES. Comparing ES and SA, we
      found that differences in mortality, poor outcomes, and rebleeding were
      insignificant, but ES had a greater evacuation rate and SA had shorter operative
      times. CONCLUSIONS: ES achieves a better performance than craniotomy and
      conservation in terms of reducing mortality, dependence, and specific
      complications. Despite being similarly effective in improving functional
      outcomes, ES and SA have respective advantages. ES is a feasible alternation to
      craniotomy and conservation, and the comparison between ES and SA warrants
      further study.

PMID- 29452328
TI  - Louis Victor Leborgne ("Tan").
AB  - Louis Victor Leborgne was a patient of Paul Broca. "Monsieur Leborgne," as Broca
      would call him, was also known around in the hospital by the nickname "Tan." His
      neurologic condition left him with difficulty in speaking, and he could only
      speak the word "Tan." Leborgne spent nearly half of his entire life in the
      hospital. He was initially admitted into the psychiatry division of the hospital
      and was later transferred under the care of Broca toward the end of his life. The
      story of the Leborgne sits in the crossroads of human thoughts that led to the
      discovery of cerebral localization. It is the objective of this study to describe
      the circumstances associated with this patient, which led the great thinkers of
      that time to discover the language localization in the cerebral cortex.
      Leborgne's condition was the cornerstone in the evolution of this discovery. More
      than 150 years have passed since the death of Leborgne, yet Leborgne's brain
      continues to attract researchers investigating the mysteries of human speech.

PMID- 29452329
TI  - Frontal Sinus Osteoma Accompanied by Intracranial Mucocele and Local Hyperostosis
      Frontalis Interna.
AB  - Frontal sinus osteoma accompanied by intracranial mucocele and local hyperostosis
      frontalis interna has never been reported. A 47-year-old woman presented with a 3
      month history of intermittent headache. Physical examination revealed no
      neurologic abnormality. Contrasted magnetic resonance imaging showed a frontal
      heterogeneously enhanced lesion with adjacent nonenhanced cyst. Computed
      tomography showed a bone density mass, which was accompanied by local
      hyperostosis frontalis interna, which filled the left frontal sinus and extended
      intracranially. The patient underwent a left frontobasal craniotomy. Both the
      osseous mass and cyst capsule were removed totally via a frontal craniotomy,
      followed by skull base reconstruction. The postoperative course was uneventful.
      The final pathologic diagnosis was osteoma and mucocele.

PMID- 29452330
TI  - Atypical Teratoid/Rhabdoid Tumor After In Vitro Fertilization: Illustrative Case
      Report and Systematic Literature Review.
AB  - OBJECTIVE: In vitro fertilization (IVF) is increasingly used for the treatment of
      infertile couples worldwide. The association between IVF and cancer risk in
      offspring is conflicting. We present a case of atypical teratoid/rhabdoid tumor
      (AT/RT) in a girl conceived by IVF and present results of systematic review of
      literature of primary intracranial neoplasms diagnosed in children conceived by
      IVF. METHODS: A systematic review of literature was conducted on April 12, 2017,
      to identify previously published reports of intracranial brain tumors in patients
      conceived after IVF. RESULTS: A 21-month-old girl born after IVF and uneventful
      pregnancy presented with progressive nausea, vomiting, irritability, and right
      side weakness. Magnetic resonance imaging demonstrated large heterogeneous
      contrast enhancing left frontotemporoparietal tumor. The operation was aborted
      due to asystole after subtotal tumor removal. The patient passed away on
      postoperative day 3. Histologic examination demonstrated AT/RT. We identified 7
      previously published case reports of intracranial neoplasms in children conceived
      by IVF. Patient age at brain tumor diagnosis ranged from 31st week of gestation
      to 3 years of age. The most common histological diagnosis was AT/RT (3 cases),
      followed by glioblastoma multiforme, gliosarcoma, medulloblastoma,
      craniopharyngioma, and choroid plexus papilloma. Three of five operated patients
      died during perioperative period. Outcomes were dismal in 7 patients.
      CONCLUSIONS: IVF-associated brain tumors are usually malignant and associated
      with high mortality. Future studies investigating possible causal relationship
      between IVF and brain tumor risk are encouraged.

PMID- 29452331
TI  - Reproducibility of sub-acromial impingement tests, including a new clinical
      manoeuver.
AB  - BACKGROUND: The Neer, Hawkins, and Yocum clinical tests detect sub-acromial
      impingement as a pathogenic process of degenerative rotator cuff disease. Their
      reproducibility has been little investigated. OBJECTIVES: We tested the
      reproducibility of the Neer, Hawkins, and Yocum clinical tests for detecting this
      sub-acromial impingement and also an original clinical manoeuver, the countertest
      with elevation with lateral rotation (CELR), which is a test of sub-acromial
      impingement. METHODS: Patients with shoulder pain due to degenerative rotator
      cuff disease were prospectively included. They were assessed with the Neer,
      Hawkins and Yocum tests as well as the CELR twice at a 1 week interval. Intra-
      and inter-observer reproducibility was assessed by percentage agreement and the
      kappa coefficient of concordance with 95% confidence intervals (CIs). Concordance
      was poor with kappa <=0.4, moderate >0.4, and good >0.61. It was considered
      suitable for clinical use with kappa >0.4. RESULTS: We included 34 patients (mean
      [SD] age 60 [11] years; 26 females). For intra-observer reproducibility,
      agreement was 80% to 88%. By the kappa coefficient, intra-observer
      reproducibility was poor for the Neer test and moderate for the Hawkins test
      (0.56 [95% CI 0;0.9]) and Yocum test (0.48 [0;0.8]) and CELR (0.6 [0.2;0.9]). For
      inter-observer reproducibility, agreement was 73% to 88%. By the kappa
      coefficient, inter-observer reproducibility was poor for the Yocum test, moderate
      for the Hawkins test (0.54 [0.2;0.8]) and CELR (0.58 [0.2;0.8]), and good for the
      Neer test (0.64 [0.2;0.9]). CONCLUSION: The Hawkins test and CELR had a balanced
      profile of reproducibility suitable for clinical practice. We underline the
      potential interest of CELR, an original manoeuver.

PMID- 29452332
TI  - Ultrasound-guided erector spinae plane block provides effective perioperative
      analgesia and anaesthesia for thoracic mass excision: A report of two cases.

PMID- 29452333
TI  - Male requires a higher median target effect-site concentration of propofol for I
      gel placement when combined with dexmedetomidine.
AB  - OBJECTIVE: The supraglottic airway device (SAD) can be used for airway management
      of spontaneous breathing patients, and propofol is commonly applied for the SAD
      placement. This study was designed to assess the effect of gender on median
      target effect-site concentration (Ce50) of propofol for I-gel placement when
      combined with dexmedetomidine. MATERIAL AND METHOD: 19 males and 18 females, aged
      18 to 59 and undergoing elective surgery, were enrolled. After intravenous
      infusion of dexmedetomidine 1.0MUg/kg over 10min followed by continuous infusion
      of 0.4MUg/kg/h, target-controlled infusion of propofol under Marsh model was
      started and the initial Ce of propofol was set at 4.79MUg/mL and 4.35MUg/mL in
      the male and female patients, respectively. The I-gel was inserted when the Ce of
      propofol reached the pre-set concentration and bispectral index value was less
      than 60. The Ce of propofol required for I-gel placement was determined by the
      Dixon up-and-down method. RESULTS: The Ce50 (95% confidence interval) of propofol
      required for I-gel placement were 4.082MUg/mL (3.798-4.332MUg/mL) and 3.509MUg/mL
      (3.266-3.749MUg/mL) in male and female patients, respectively, with a
      significantly higher Ce50 in males. CONCLUSION: When combined with
      dexmedetomidine, males require a higher Ce50 of propofol for I-gel placement
      compared to females.

PMID- 29452334
TI  - SEED 2: a user-friendly platform for amplicon high-throughput sequencing data
      analyses.
AB  - Motivation: Modern molecular methods have increased our ability to describe
      microbial communities. Along with the advances brought by new sequencing
      technologies, we now require intensive computational resources to make sense of
      the large numbers of sequences continuously produced. The software developed by
      the scientific community to address this demand, although very useful, require
      experience of the command-line environment, extensive training and have steep
      learning curves, limiting their use. We created SEED 2, a graphical user
      interface for handling high-throughput amplicon-sequencing data under Windows
      operating systems. Results: SEED 2 is the only sequence visualizer that empowers
      users with tools to handle amplicon-sequencing data of microbial community
      markers. It is suitable for any marker genes sequences obtained through Illumina,
      IonTorrent or Sanger sequencing. SEED 2 allows the user to process raw sequencing
      data, identify specific taxa, produce of OTU-tables, create sequence alignments
      and construct phylogenetic trees. Standard dual core laptops with 8 GB of RAM can
      handle ca. 8 million of Illumina PE 300 bp sequences, ca. 4 GB of data.
      Availability and implementation: SEED 2 was implemented in Object Pascal and uses
      internal functions and external software for amplicon data processing. SEED 2 is
      a freeware software, available at http://www.biomed.cas.cz/mbu/lbwrf/seed/ as a
      self-contained file, including all the dependencies, and does not require
      installation. Supplementary data contain a comprehensive list of supported
      functions. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29452335
TI  - Change in cardiometabolic risk among blacks, whites and Hispanics: findings from
      the Health and Retirement Study.
AB  - Background: Blacks experience greater multi-system physiological dysregulation,
      or cumulative biological risk, which is associated with poor cardiometabolic
      health and mortality. In this study, we assess race differences in change in risk
      over four years among older whites, blacks and Hispanics. Method: We examined
      race differences in 4-year change in individual biomarkers and a cumulative
      measure of risk-cardiometabolic risk (CMR)-using data for each respondent from
      two waves of the Health and Retirement Study's biomarker assessment (n=5,512).
      CMR is a count of high-risk cardiovascular and metabolic biomarkers. We estimated
      mean CMR at baseline and follow-up by race/ethnicity, and used logistic
      regression to determine whether race differences exist in 4-year transitions
      between high- and low-risk states for individual biomarkers. Results: Blacks had
      higher baseline CMR than whites and Hispanics and experienced an increase in risk
      over four years; conversely, CMR decreased among whites and Hispanics. Blacks
      were more likely to develop high-risk pulse pressure and high-risk hemoglobin
      A1c, which contributed to increases in CMR. Whites and Hispanics were more likely
      to become low-risk on C-reactive protein and HDL cholesterol which contributed to
      declines in CMR. Race differences in transitions between risk states remained
      after controlling for social, behavioral and health care related factors.
      However, the racial patterning of these differences was influenced by disease
      diagnosis and medication use. Conclusions: We show that the cardiometabolic
      health of older blacks worsens as they age both absolutely and relative to that
      of whites and Hispanics because of poor blood pressure control and diabetes
      prevention.

PMID- 29452337
TI  - Commentary on: Oral Contraceptive Management in Aesthetic Surgery: A Survey of
      Current Practice Trends.

PMID- 29452336
TI  - Invited Commentary: Male Reproductive System Congenital Malformations and the
      Risk of Autism Spectrum Disorder.
AB  - Autism spectrum disorder (ASD) is a prevalent developmental disorder. Studies
      indicate that while ASD etiology has a genetic component, the risk is polygenic,
      with gene-environment interactions being likely. The prenatal period is a
      critical exposure window for nongenetic risk factors. Previous studies have found
      positive associations between congenital malformations (all types) and ASD; a few
      also found specific associations between genitourinary system malformations and
      ASD; and one study found an association between hypospadias and ASD. In the
      accompanying article, Rotem et al. (Am J Epidemiol. 2018;187(4):656-663) describe
      how they conducted a comprehensive analysis focusing on the shared risk of ASD
      with hypospadias or cryptorchidism, using existing data from a large Israeli
      health services system, which afforded several advantages because of the large
      sample size and low attrition of the patient population. The authors conducted a
      careful analysis, including sensitivity analyses, to account for risk factor and
      case misclassifications that might have occurred had they relied solely on
      preexisting diagnostic codes to define exposures and outcome. They observed
      positive associations between both hypospadias and cryptorchidism and ASD that
      were independent of numerous sociodemographic and pregnancy health factors. This
      study advances our understanding of ASD etiology and illustrates how existing
      data might be used to assess some ASD risk factors.

PMID- 29452338
TI  - Potential benefits of prasugrel and ticagrelor is diabetics are not substantiated
      by the Food and Drug Administration adverse event repository.

PMID- 29452339
TI  - Using light to fight atrial fibrillation.

PMID- 29452340
TI  - Congenital Abnormalities of the Male Reproductive System and Risk of Autism
      Spectrum Disorders.
AB  - Androgens have an extensive influence on brain development in regions of the
      brain that are relevant for autism spectrum disorder (ASD), yet their etiological
      involvement remains unclear. Hypospadias (abnormal positioning of the urethral
      opening) and cryptorchidism (undescended testes) are 2 relatively common male
      birth defects that are strongly associated with prenatal androgen deficiencies.
      Having either disorder is a proxy indicator of atypical gestational androgen
      exposure, yet the association between these disorders and autism has not been
      extensively studied. We analyzed male singleton live births (n = 224,598)
      occurring from January 1, 1999, through December 31, 2013, in a large Israeli
      health-care organization. Boys with autism, cryptorchidism, and hypospadias were
      identified via International Classification of Diseases, Ninth Revision, codes,
      with further verification of autism case status by review of medical records. In
      multivariable-adjusted analyses, the odds ratio for ASD among boys with either
      condition was 1.62 (95% confidence interval (CI): 1.44, 1.82). The odds ratio for
      boys with cryptorchidism only was 1.55 (95% CI: 1.34, 1.78), and that for boys
      with hypospadias only was 1.65 (95% CI: 1.38, 1.98). ASD risk was not elevated
      among unaffected brothers of hypospadias or cryptorchidism cases, despite
      familial aggregation of all 3 conditions, providing some indication for the
      possibility of pregnancy-specific risk factors driving the observed associations.
      Results suggest that in-utero hypoandrogenicity could play a role in ASD
      etiology.

PMID- 29452341
TI  - Betadine and Breast Implants.
AB  - In the fourth quarter of 2017, the US FDA reviewed and approved a request by one
      of the breast implant manufacturers for a change in the Directions for Use (DFU)
      that removed warnings regarding the use of Betadine (povidone-iodine [PI] 10%
      solution, 1% available iodine [Purdue Frederick Company, Stamford, CT], also
      available in generic formulations [Aplicare, Inc., Meriden, CT]). Previously, in
      2000, there were concerns by the FDA that PI would degrade the silicone elastomer
      shell. This change in the DFU represents an important advance that will benefit
      patients through the permitted use of PI to reduce the risk of bacterial
      contamination of implant surfaces. What was formerly an off-label practice can be
      openly practiced by plastic surgeons as an anti-infective and biofilm-mitigation
      strategy. PI has an ideal spectrum effect for gram-positive and gram-negative
      organisms. Gram-positive organisms have been linked to capsular contracture and
      gram-negative Ralstonia picketti to breast implant-associated anaplastic large
      cell lymphoma (BIA-ALCL). R picketti is resistant to aminoglycoside antibiotics,
      but it is susceptible to at least a 50% solution of PI. We believe that the
      strategy of antisepsis and biofilm mitigation is an integral part of a
      contemporary approach for breast augmentation. This is beneficial regarding
      reduction of the risk of surgical infection, capsular contracture, and BIA-ALCL.
      Outcome data so far indicate that antibiotics/anti-infectives seem to reduce the
      incidence of these adverse events that lead to reoperation and increased costs.
      It behooves plastic surgeons to take all actionable steps that enhance the
      quality of breast implant outcomes and reduce the rate of reoperation.

PMID- 29452342
TI  - Neurofilament light chain and oligoclonal bands are prognostic biomarkers in
      radiologically isolated syndrome.
AB  - The prognostic role of cerebrospinal fluid molecular biomarkers determined in
      early pathogenic stages of multiple sclerosis has yet to be defined. In the
      present study, we aimed to investigate the prognostic value of chitinase 3 like 1
      (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to
      clinically isolated syndrome and to multiple sclerosis in 75 patients with
      radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and
      neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni
      and multivariable Cox regression models including as covariates age at diagnosis
      of radiologically isolated syndrome, number of brain lesions, sex and treatment
      were used to investigate associations between cerebrospinal fluid CHI3L1 and
      neurofilament light chain levels and time to conversion to clinically isolated
      syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal
      bands were independent risk factors for the development of clinically isolated
      syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012,
      respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard
      ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal
      fluid neurofilament light chain levels into high and low was 619 ng/l, and high
      neurofilament light chain levels were associated with a trend to shorter time to
      clinically isolated syndrome (P = 0.079) and significant shorter time to multiple
      sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome
      presenting positive oligoclonal bands converted faster to clinically isolated
      syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The
      effects of high neurofilament light chain levels shortening time to clinically
      isolated syndrome and multiple sclerosis were more pronounced in radiologically
      isolated syndrome patients with >=37 years compared to younger patients.
      Cerebrospinal fluid CHI3L1 levels did not influence conversion to clinically
      isolated syndrome and multiple sclerosis in radiologically isolated syndrome
      patients. Overall, these findings suggest that cerebrospinal neurofilament light
      chain levels and oligoclonal bands are independent predictors of clinical
      conversion in patients with radiologically isolated syndrome. The association
      with a faster development of multiple sclerosis reinforces the importance of
      cerebrospinal fluid analysis in patients with radiologically isolated syndrome.

PMID- 29452343
TI  - Height-Based Equations Can Improve the Diagnosis of Elevated Blood Pressure in
      Children.
AB  - Background: High blood pressure (BP) is usually underdiagnosed in children and
      adolescents, particularly due to its complex diagnosis process. This study
      describes novel height-based equations for the detection of BP disorders (BP >
      90th percentile) and compares the accuracy of this approach with previously
      described screening methods to identify BP disorders. Methods: Height-based
      equations were built using the 90th percentile values for systolic and diastolic
      BP and respective height values from the current guideline of high-BP management
      in children. This guideline was also used as the gold standard method for
      identification of BP disorders. The equations were tested in Brazilian (n =
      2,936) and American (n = 6,541) populations of children with 8-13 years old.
      Results: The obtained equations were 70 + 0.3 * height (in cm) for systolic BP
      and 35 + 0.25 * height (in cm) for diastolic BP. The new equations presented
      sensitivity and negative predictive value of near 100% and specificity > 91% and
      showed higher specificity and positive predictive value when compared with other
      screening tools. Importantly, height-based equations had greater agreement (kappa
      coefficient = 0.75-0.81) with the gold standard method than the other methods
      (kappa coefficient = 0.53-0.73). Further analysis showed that alternative height
      based equations designed to identify hypertension (BP >= 95th percentile) also
      showed superior performance (kappa coefficient = 0.89-0.92) compared with other
      screening methods (kappa coefficient = 0.43-0.85). Conclusions: These findings
      suggest that the use of height-based equations may be a simple and feasible
      approach to improve the detection of high BP in the pediatric population.

PMID- 29452344
TI  - Overexpression of BLM promotes DNA damage and increased sensitivity to platinum
      salts in triple-negative breast and serous ovarian cancers.
AB  - Background: Platinum-based therapy is an effective treatment for a subset of
      triple-negative breast cancer and ovarian cancer patients. In order to increase
      response rate and decrease unnecessary use, robust biomarkers that predict
      response to therapy are needed. Patients and methods: We performed an integrated
      genomic approach combining differential analysis of gene expression and DNA copy
      number in sensitive compared with resistant triple-negative breast cancers in two
      independent neoadjuvant cisplatin-treated cohorts. Functional relevance of
      significant hits was investigated in vitro by overexpression, knockdown and
      targeted inhibitor treatment. Results: We identified two genes, the Bloom
      helicase (BLM) and Fanconi anemia complementation group I (FANCI), that have both
      increased DNA copy number and gene expression in the platinum-sensitive cases.
      Increased level of expression of these two genes was also associated with
      platinum but not with taxane response in ovarian cancer. As a functional
      validation, we found that overexpression of BLM promotes DNA damage and induces
      sensitivity to cisplatin but has no effect on paclitaxel sensitivity.
      Conclusions: A biomarker based on the expression levels of the BLM and FANCI
      genes is a potential predictor of platinum sensitivity in triple-negative breast
      cancer and ovarian cancer.

PMID- 29452345
TI  - Daily Biopsy Diagnosis in Surgical Pathology: Concordance Between Light
      Microscopy and Whole-Slide Imaging in Real-Life Conditions.
AB  - Objectives: The current challenge for the various digital whole-slide imaging
      (WSI) systems is to be definitively validated for diagnostic purposes. We
      designed a concordance study between glass slide and digital slide diagnosis in
      real-life conditions, coupled with an ergonomic study. Methods: Three senior
      pathologists evaluated, first in glass slides and then in digital slides, 119
      biopsy cases, including 749 slides, with 332 H&E saffron stains and 417
      additional techniques, mainly immunohistochemistry. Results: All digital slides,
      including specially stained slides, were interpretable. Concordance between glass
      slides and digital slides was observed in 87.4% of cases. Minor discordances were
      observed in 12 (10.1%) cases and major discordances, with therapeutic impact, in
      three (2.5%), including one related to WSI. The satisfaction of participants was
      high and increased with time. Conclusions: Our study confirms the feasibility and
      accuracy of WSI diagnosis, even for cases having multiple samples and requiring
      special staining techniques, such as immunohistochemistry and in situ
      hybridization.

PMID- 29452347
TI  - The Importance of Clinically Relevant Research When Making Comparisons.

PMID- 29452346
TI  - Beyond second-line therapy in patients with metastatic colorectal cancer: a
      systematic review.
AB  - Background: The optimal chemotherapeutic regimen for use beyond the second line
      for patients with metastatic colorectal cancer (mCRC) remains unclear. Materials
      and methods: We systematically searched the Cochrane Database of Systematic
      Reviews, EMBASE and Medline for records published between January 2002 and May
      2017, and cancer congress databases for records published between January 2014
      and June 2017. Eligible studies evaluated the efficacy, safety and patient
      reported outcomes of monotherapies or combination therapies at any dose and
      number of treatment cycles for use beyond the second line in patients with mCRC.
      Studies were assessed for design and quality, and a qualitative data synthesis
      was conducted to understand the impact of treatment on overall survival and other
      relevant cancer-related outcomes. Results: The search yielded 938 references of
      which 68 were included for qualitative synthesis. There was limited evidence to
      support rechallenge with chemotherapy, targeted therapy or both. Compared with
      placebo, an overall survival benefit for trifluridine/tipiracil (also known as
      TAS-102) or regorafenib has been shown for patients previously treated with
      conventional chemotherapy and targeted therapy. There was no evidence to suggest
      a difference in efficacy between these treatments. Patient choice and quality of
      life at this stage of treatment should also be considered when choosing an
      appropriate therapy. Conclusions: These findings support the introduction of an
      approved agent such as trifluridine/tipiracil or regorafenib beyond the second
      line before any rechallenge in patients with mCRC who have failed second-line
      treatment.

PMID- 29452348
TI  - Non-invasive screening for coronary artery disease in asymptomatic diabetic
      patients: a systematic review and meta-analysis of randomised controlled trials.
AB  - It is unclear whether non-invasive screening of asymptomatic diabetic patients
      for coronary artery disease (CAD) may improve cardiac outcomes. Thus, we
      performed a systematic literature review and meta-analysis of randomised
      controlled trials (RCT's) on this topic. We searched appropriate RCT's in five
      online databases (PubMed/MEDLINE, Cochrane Library, Embase, Scopus, and Web of
      Science) from January 2000 to November 2017 and in 41 recent reviews. Two
      investigators independently extracted and assessed study data using standardised
      forms. Additional unpublished data were obtained from trial authors. The primary
      endpoint 'any cardiac event' was a composite of cardiac death, non-fatal
      myocardial infarction (MI), unstable angina (UA), or heart failure (HF)
      hospitalisation. We performed a meta-analysis of relative risks (RRs) with 95%
      confidence intervals (CI) using the Mantel-Haenszel method. We included five
      RCT's with 3299 patients, of which 189 (5.7%) experienced any cardiac event on
      follow-up (weighted mean 4.1 years). Non-invasive CAD screening significantly
      reduced any cardiac event by 27% [RR 0.73 (95% CI 0.55-0.97), P = 0.028, number
      needed to screen 56]. This result was driven by important, albeit non-significant
      decreases in non-fatal MI [RR 0.65 (95% CI 0.41-1.02), P = 0.062] and HF
      hospitalisation [RR 0.61 (95% CI 0.33-1.10), P = 0.100]. Non-invasive CAD
      screening did not significantly affect cardiac death [RR 0.92 (95% CI 0.53-1.60),
      P = 0.77] and UA [RR 0.73 (95% CI 0.41-1.31), P = 0.29]. Compared with the
      standard care, non-invasive CAD screening reduced cardiac events by 27% in
      asymptomatic diabetic patients, largely through reductions in non-fatal MIs, and
      HF hospitalisations. The present results justify larger, appropriately powered
      trials to potentially revisit current recommendations.

PMID- 29452349
TI  - Non-genomic effects of nuclear receptors: insights from the anucleate platelet.
AB  - Nuclear receptors (NRs) have the ability to elicit two different kinds of
      responses, genomic and non-genomic. Although genomic responses control gene
      expression by influencing the rate of transcription, non-genomic effects occur
      rapidly and independently of transcriptional regulation. Due to their anucleate
      nature and mechanistically well-characterized and rapid responses, platelets
      provide a model system for the study of any non-genomic effects of the NRs.
      Several NRs have been found to be present in human platelets, and multiple NR
      agonists have been shown to elicit anti-platelet effects by a variety of
      mechanisms. The non-genomic functions of NRs vary, including the regulation of
      kinase and phosphatase activity, ion channel function, intracellular calcium
      levels, and production of second messengers. Recently, the characterization of
      mechanisms and identification of novel binding partners of NRs have further
      strengthened the prospects of developing their ligands into potential
      therapeutics that offer cardio-protective properties in addition to their other
      defined genomic effects.

PMID- 29452350
TI  - Extra-virgin olive oil contains a metabolo-epigenetic inhibitor of cancer stem
      cells.
AB  - Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC)
      with phytochemicals is a novel paradigm for cancer prevention and treatment. We
      herein employed a phenotypic drug discovery approach coupled to mechanism-of
      action profiling and target deconvolution to identify phenolic components of
      extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC
      in breast cancer (BC). In vitro screening revealed that the secoiridoid
      decarboxymethyl oleuropein aglycone (DOA) could selectively target subpopulations
      of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like,
      CD44+CD24-/low CSC. DOA could potently block the formation of multicellular
      tumorspheres generated from single-founder stem-like cells in a panel of
      genetically diverse BC models. Pretreatment of BC populations with noncytotoxic
      doses of DOA dramatically reduced subsequent tumor-forming capacity in vivo. Mice
      orthotopically injected with CSC-enriched BC-cell populations pretreated with DOA
      remained tumor-free for several months. Phenotype microarray-based screening
      pointed to a synergistic interaction of DOA with the mTOR inhibitor rapamycin and
      the DNA methyltransferase (DNMT) inhibitor 5-azacytidine. In silico computational
      studies indicated that DOA binds and inhibits the ATP-binding kinase domain site
      of mTOR and the S-adenosyl-l-methionine (SAM) cofactor-binding pocket of DNMTs.
      FRET-based Z-LYTETM and AlphaScreen-based in vitro assays confirmed the ability
      of DOA to function as an ATP-competitive mTOR inhibitor and to block the SAM
      dependent methylation activity of DNMTs. Our systematic in vitro, in vivo and in
      silico approaches establish the phenol-conjugated oleoside DOA as a dual
      mTOR/DNMT inhibitor naturally occurring in EVOO that functionally suppresses CSC
      like states responsible for maintaining tumor-initiating cell properties within
      BC populations.

PMID- 29452351
TI  - Impact of treatment delay on mortality in ST-segment elevation myocardial
      infarction (STEMI) patients presenting with and without haemodynamic instability:
      results from the German prospective, multicentre FITT-STEMI trial.
AB  - Aims: The aim of this study was to investigate the effect of contact-to-balloon
      time on mortality in ST-segment elevation myocardial infarction (STEMI) patients
      with and without haemodynamic instability. Methods and results: Using data from
      the prospective, multicentre Feedback Intervention and Treatment Times in ST
      Elevation Myocardial Infarction (FITT-STEMI) trial, we assessed the prognostic
      relevance of first medical contact-to-balloon time in n = 12 675 STEMI patients
      who used emergency medical service transportation and were treated with primary
      percutaneous coronary intervention (PCI). Patients were stratified by cardiogenic
      shock (CS) and out-of-hospital cardiac arrest (OHCA). For patients treated within
      60 to 180 min from the first medical contact, we found a nearly linear
      relationship between contact-to-balloon times and mortality in all four STEMI
      groups. In CS patients with no OHCA, every 10-min treatment delay resulted in
      3.31 additional deaths in 100 PCI-treated patients. This treatment delay-related
      increase in mortality was significantly higher as compared to the two groups of
      OHCA patients with shock (2.09) and without shock (1.34), as well as to
      haemodynamically stable patients (0.34, P < 0.0001). Conclusions: In patients
      with CS, the time elapsing from the first medical contact to primary PCI is a
      strong predictor of an adverse outcome. This patient group benefitted most from
      immediate PCI treatment, hence special efforts to shorten contact-to-balloon time
      should be applied in particular to these high-risk STEMI patients. Clinical Trial
      Registration: NCT00794001.

PMID- 29452353
TI  - A diagnostic germ cell score for immature testicular tissue at risk of germ cell
      loss.
AB  - STUDY QUESTION: Can a systematic scoring procedure provide crucial information on
      the status of highly heterogeneous immature human testicular tissues in the
      context of cryopreservation for fertility preservation? SUMMARY ANSWER: We
      developed a systematic histological score as a novel diagnostic tool which
      differentiates the patient cohort according to the status of germ cell
      differentiation and number of spermatogonia (normal, diminished and absent), and
      which could be relevant in the fertility clinic. WHAT IS KNOWN ALREADY:
      Cryopreservation of testicular tissue of immature boys is currently considered
      the option for future fertility restoration. However, experimental techniques for
      the derivation of sperm as well as valid diagnostic scoring of these immature
      testis tissues are not yet reported. STUDY DESIGN, SIZE, DURATION: Testicular
      tissues of 39 patients (aged 2-20 years) who attended our clinic for
      cryopreservation between 2010 and 2015 were analyzed to determine the variability
      of testicular tissue composition, germ cell numbers and differentiation status.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular tissue samples were
      divided into three groups. Group NT included patients suffering from diseases
      which do not directly affect the testes (n = 6; aged 6-14 years), group AT
      included patients suffering from diseases that directly affect the testes (n =
      14; 2-17 years), and group KS (Klinefelter patients, n = 19; 12-20 years). Based
      on immunohistochemical stainings for MAGEA4, the differentiation status as well
      as the numbers of gonocytes, spermatogonia and spermatocytes were determined.
      MAIN RESULTS AND THE ROLE OF CHANCE: Testicular tissue samples from the NT group
      contained a mean of 100.3 spermatogonia/mm3 (*103). Highly heterogeneous and
      significantly lower mean numbers of spermatogonia were scored in testes from boys
      after cytotoxic exposures or with pre-existing disease (AT group: 35.7
      spermatogonia/mm3 (*103); KS group: 1.8 spermatogonia/mm3 (*103)). In addition,
      the germ cell differentiation status was determined and revealed tissues with
      either spermatogonia and gonocytes, only spermatogonia, spermatogonia and
      spermatocytes, or all three germ cell types were present. Based on spermatogonial
      numbers and differentiation status, we developed a germ cell score which we
      applied to each individual patient sample. LIMITATIONS REASONS FOR CAUTION:
      Normal human testicular tissue samples are difficult to obtain for ethical
      reasons and the sample numbers were small. However, six such samples provide a
      valid baseline for the normal situation. WIDER IMPLICATIONS OF THE FINDINGS:
      Fertility preservation of immature male tissues is an emerging field and is
      currently offered in many specialized centers worldwide. Our diagnostic germ cell
      score delivers an easily applicable tool, facilitating patient counseling and
      thus ensuring comparability between the centers with regard to future studies.
      STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Funding
      Initiative: Translational Research, Ministry of Innovation, Science and Research,
      Federal State of North Rhine Westphalia (z1403ts006). The authors declare that
      they do not have competing financial interests.

PMID- 29452352
TI  - Conditional ablation and conditional rescue models for Casq2 elucidate the role
      of development and of cell-type specific expression of Casq2 in the CPVT2
      phenotype.
AB  - Cardiac calsequestrin (Casq2) associates with the ryanodine receptor 2 channel in
      the junctional sarcoplasmic reticulum to regulate Ca2+ release into the
      cytoplasm. Patients carrying mutations in CASQ2 display low resting heart rates
      under basal conditions and stress-induced polymorphic ventricular tachycardia
      (CPVT). In this study, we generate and characterize novel conditional deletion
      and conditional rescue mouse models to test the influence of developmental
      programs on the heart rate and CPVT phenotypes. We also compare the requirements
      for Casq2 function in the cardiac conduction system (CCS) and in working
      cardiomyocytes. Our study shows that the CPVT phenotype is dependent upon
      concurrent loss of Casq2 function in both the CCS and in working cardiomyocytes.
      Accordingly, restoration of Casq2 in only the CCS prevents CPVT. In addition,
      occurrence of CPVT is independent of the developmental history of Casq2
      deficiency. In contrast, resting heart rate depends upon Casq2 gene activity only
      in the CCS and upon developmental history. Finally, our data support a model
      where low basal heart rate is a significant risk factor for CPVT.

PMID- 29452354
TI  - Alpha-synuclein inhibits Snx3-retromer-mediated retrograde recycling of iron
      transporters in S. cerevisiae and C. elegans models of Parkinson's disease.
AB  - We probed the role of alpha-synuclein (alpha-syn) in modulating sorting nexin 3
      (Snx3)-retromer-mediated recycling of iron transporters in Saccharomyces
      cerevisiae and Caenorhabditis elegans. In yeast, the membrane-bound heterodimer
      Fet3/Ftr1 is the high affinity iron importer. Fet3 is a membrane-bound
      multicopper ferroxidase, whose ferroxidase domain is orthologous to human
      ceruloplasmin (Cp), that oxidizes external Fe+2 to Fe+3; the Fe+3 ions then
      channel through the Ftr1 permease into the cell. When the concentration of
      external iron is low (<1 uM), Fet3/Ftr1 is maintained on the plasma membrane by
      retrograde endocytic-recycling; whereas, when the concentration of external iron
      is high (>10 uM), Fet3/Ftr1 is endocytosed and shunted to the vacuole for
      degradation. We discovered that alpha-syn expression phenocopies the high iron
      condition: under the low iron condition (<1 uM), alpha-syn inhibits Snx3-retromer
      mediated recycling of Fet3/Ftr1 and instead shunts Fet3/Ftr1 into the
      multivesicular body pathway to the vacuole. alpha-Syn inhibits recycling by
      blocking the association of Snx3-mCherry molecules with endocytic vesicles,
      possibly by interfering with the binding of Snx3 to phosphatidylinositol-3
      monophosphate. In C. elegans, transgenic worms expressing alpha-syn exhibit an
      age-dependent degeneration of dopaminergic neurons that is partially rescued by
      the iron chelator desferoxamine. This implies that alpha-syn-expressing
      dopaminergic neurons are susceptible to changes in iron neurotoxicity with age,
      whereby excess iron enhances alpha-syn-induced neurodegeneration. In vivo genetic
      analysis indicates that alpha-syn dysregulates iron homeostasis in worm
      dopaminergic neurons, possibly by inhibiting SNX-3-mediated recycling of a
      membrane-bound ortholog of Cp (F21D5.3), the iron exporter ferroportin (FPN1.1),
      or both.

PMID- 29452356
TI  - Baseline anticholinergic burden from medications predicts incident fatal and non
      fatal stroke in the EPIC-Norfolk general population.
AB  - Background: Stroke is primarily a disease of older age, with a substantial impact
      on global mortality and morbidity. Medications with anticholinergic effects are
      widely used, but no studies have been conducted to examine the relationship
      between anticholinergic burden (ACB) and stroke in a general population. Method:
      The sample was drawn from the EPIC-Norfolk cohort. Baseline assessments were
      carried out during 1993-97 and participants were followed up until March 2016.
      Participants were divided into four groups according to their total ACB score at
      baseline; these groups were those with a total ACB score of 0, 1, 2-3 and >3.
      After exclusion, Cox proportional hazards models were constructed to determine
      the associations between the ACB score groups and the risk of incident stroke and
      stroke mortality. Sensitivity analysis and propensity score matched analyses were
      performed. Results: In total 25 639 participants attended the first health check;
      3917 participants were excluded, leaving 21 722 participants to be included.
      Participants had a mean age [standard deviation (SD)] of 58.9 (9.2) years (54.4%
      women). Of these, 2131 suffered incident stroke and 562 died from stroke. Mean
      follow-up was approximately 18 years for both outcomes. In the fully adjusted
      model, those with an ACB of >3 had 59% relative risk of incident stroke {hazard
      ratio [HR] [95% confidence interval (CI) 1.59 [1.34-1.89]} and 86% relative risk
      of stroke mortality [1.86 (1.37-2.53)] compared with those in ACB 0 category.
      Sensitivity analyses and propensity score matched analyses showed similar
      results. Conclusions: Our results provide an incentive for the cautious use of
      medications with anticholinergic properties, to help reduce the global burden of
      stroke.

PMID- 29452357
TI  - del Nido cardioplegia in adult cardiac surgery: beyond single-valve surgery.
AB  - OBJECTIVES: In recent years, the use of del Nido (DN) cardioplegia has been
      reported in single-valve surgery or isolated coronary artery bypass surgery with
      acceptable outcomes. The reports of its use in more complex adult cardiac
      procedures, however, have been scarce. METHODS: We enrolled a total of 149 adult
      patients who underwent heart valve surgery with the use of DN cardioplegia
      between May 2014 and December 2016. For a benchmark comparison, 892 patients who
      underwent cardiac valve surgery with blood cardioplegia during the same period
      served as controls. To reduce selection bias, propensity score matching was used;
      the inverse probability of treatment weighting method was performed for further
      validations. RESULTS: Overall, 57.7% of patients in the DN group underwent
      multiple or complex cardiac procedures. Early mortality rates were 0.7% and 2.4%
      in the DN and blood groups, respectively (P = 0.31). Propensity score matching
      yielded 111 pairs of patients who were well balanced for all 23 measured baseline
      covariates. In the matched cohort, the postoperative peak troponin I levels (P =
      0.004) and the aortic clamping times (P < 0.001) were significantly lower and
      shorter compared with those in the blood group. There were no significant
      differences in early mortality rates (1.9% vs 0%, P > 0.99), low cardiac output
      (P = 0.57) and neurological events (P = 0.21). The quantities of postoperative
      transfusions (P = 0.008) and fluid supplements (P < 0.001) were significantly
      lower in the matched DN group compared with the blood group. CONCLUSIONS: The use
      of DN in adult valve surgery including complex procedures may confer acceptable
      outcomes comparable to or even superior to those obtained with the use of blood
      cardioplegia.

PMID- 29452358
TI  - Reperfusion delay in patients with high-risk ST-segment elevation myocardial
      infarction: every minute counts, much more than suspected.

PMID- 29452355
TI  - Culture-Facilitated Comparative Genomics of the Facultative Symbiont Hamiltonella
      defensa.
AB  - Many insects host facultative, bacterial symbionts that confer conditional
      fitness benefits to their hosts. Hamiltonella defensa is a common facultative
      symbiont of aphids that provides protection against parasitoid wasps. Protection
      levels vary among strains of H. defensa that are also differentially infected by
      bacteriophages named APSEs. However, little is known about trait variation among
      strains because only one isolate has been fully sequenced. Generating complete
      genomes for facultative symbionts is hindered by relatively large genome sizes
      but low abundances in hosts like aphids that are very small. Here, we took
      advantage of methods for culturing H. defensa outside of aphids to generate
      complete genomes and transcriptome data for four strains of H. defensa from the
      pea aphid Acyrthosiphon pisum. Chosen strains also spanned the breadth of the H.
      defensa phylogeny and differed in strength of protection conferred against
      parasitoids. Results indicated that strains shared most genes with roles in
      nutrient acquisition, metabolism, and essential housekeeping functions. In
      contrast, the inventory of mobile genetic elements varied substantially, which
      generated strain specific differences in gene content and genome architecture. In
      some cases, specific traits correlated with differences in protection against
      parasitoids, but in others high variation between strains obscured identification
      of traits with likely roles in defense. Transcriptome data generated continuous
      distributions to genome assemblies with some genes that were highly expressed and
      others that were not. Single molecule real-time sequencing further identified
      differences in DNA methylation patterns and restriction modification systems that
      provide defense against phage infection.

PMID- 29452360
TI  - The role of transvenous lead extraction in the management of redundant or
      malfunctioning pacemaker and defibrillator leads post ELECTRa.
AB  - Cardiac implantable electronic devices implantation rates have increased over the
      past decade due to broader indications and an ageing population. Similarly,
      device and lead complications have also risen. The management of
      pacemaker/defibrillator leads that are no longer required (redundant) or
      malfunctioning, can be contentious. There is a need to balance the risk of
      transvenous lead extraction (TLE) against those of lead abandonment. The recently
      published European Lead Extraction ConTRolled Registry (ELECTRa) study provides
      contemporary outcomes for TLE across Europe with important implications for the
      management of redundant and/or malfunctioning leads. This review article
      discusses the potential complications for each interventional approach when
      managing redundant or malfunctioning pacemaker leads.

PMID- 29452359
TI  - Convergent Amino Acid Signatures in Polyphyletic Campylobacter jejuni
      Subpopulations Suggest Human Niche Tropism.
AB  - Human infection with the gastrointestinal pathogen Campylobacter jejuni is
      dependent upon the opportunity for zoonotic transmission and the ability of
      strains to colonize the human host. Certain lineages of this diverse organism are
      more common in human infection but the factors underlying this overrepresentation
      are not fully understood. We analyzed 601 isolate genomes from agricultural
      animals and human clinical cases, including isolates from the multihost
      (ecological generalist) ST-21 and ST-45 clonal complexes (CCs). Combined
      nucleotide and amino acid sequence analysis identified 12 human-only amino acid
      KPAX clusters among polyphyletic lineages within the common disease causing CC21
      group isolates, with no such clusters among CC45 isolates. Isolate sequence types
      within human-only CC21 group KPAX clusters have been sampled from other hosts,
      including poultry, so rather than representing unsampled reservoir hosts, the
      increase in relative frequency in human infection potentially reflects a genetic
      bottleneck at the point of human infection. Consistent with this, sequence
      enrichment analysis identified nucleotide variation in genes with putative
      functions related to human colonization and pathogenesis, in human-only clusters.
      Furthermore, the tight clustering and polyphyly of human-only lineage clusters
      within a single CC suggest the repeated evolution of human association through
      acquisition of genetic elements within this complex. Taken together, combined
      nucleotide and amino acid analysis of large isolate collections may provide clues
      about human niche tropism and the nature of the forces that promote the emergence
      of clinically important C. jejuni lineages.

PMID- 29452361
TI  - IUI: review and systematic assessment of the evidence that supports global
      recommendations.
AB  - BACKGROUND: IUI with or without ovarian stimulation (OS) has become a first-line
      treatment option for many infertile couples, worldwide. The appropriate treatment
      modality for couples and their clinical management through IUI or IUI/OS cycles
      must consider maternal and perinatal outcomes, most notably the clinical
      complication of higher-order multiple pregnancies associated with IUI-OS. With a
      current global emphasis to continue to decrease maternal and perinatal mortality
      and morbidity, the World Health Organization (WHO) had established a multi-year
      project to review the evidence for the establishment of normative guidance for
      the implementation of IUI as a treatment to address fertility problems, and to
      consider its cost-effectiveness for lower resource settings. OBJECTIVE AND
      RATIONALE: The objective of this review is to provide a review of the evidence of
      13 prioritized questions that cover IUI with and without OS. We provide summary
      recommendations for the development of global, evidence-based guidelines based
      upon methodology established by the WHO. SEARCH METHODS: We performed a
      comprehensive search using question-specific relevant search terms in May 2015.
      For each PICO (Population, Intervention, Comparison and Outcomes) drafted by WHO,
      specific search terms were used to find the available evidence in MEDLINE (1950
      to May 2015) and The Cochrane Library (until May 2015). After presentation to an
      expert panel, a further hand search of references in relevant reviews was
      performed up to January 2017. Articles that were found to be relevant were read
      and analysed by two investigators and critically appraised using the Cochrane
      Collaboration's tool for assessing risk of bias, and AMSTAR in case of systematic
      reviews. The quality of the evidence was assessed using the GRADE system. An
      independent expert review process of our analysis was conducted in November 2016.
      OUTCOMES: This review provides an assessment and synthesis of the evidence that
      covers 13 clinical questions including the indications for the use of IUI versus
      expectant management, the sperm parameters required, the best and optimal method
      of timing and number of inseminations per cycle, prevention strategies to
      decrease multiple gestational pregnancies, and the cost-effectiveness of IUI
      versus IVF. We provide an evidence-based formulation of 20 recommendations, as
      well as two best practice points that address the integration of methods for the
      prevention of infection in the IUI laboratory. The quality of the evidence ranges
      from very low to high, with evidence that may be decades old but of high quality,
      however, we further discuss where critical research gaps in the evidence remain.
      WIDER IMPLICATIONS: This review presents an evidence synthesis assessment and
      includes recommendations that will assist health care providers worldwide with
      their decision-making when considering IUI treatments, with or without OS, for
      their patients presenting with fertility problems.

PMID- 29452362
TI  - Reported theory use in walking interventions: a literature review and research
      agenda.
AB  - There is mixed evidence with some suggesting walking can be increased up to the
      recommended level through interventions based on behaviour change models and
      others showing partial or no effects [Arbour and Ginis (A randomised controlled
      trial of the effects of implementation intentions on women's walking behaviour.
      Psychol Health, 2009;24:49-65); Merom et al. (Can a motivational intervention
      overcome an unsupportive environment for walking-findings from the Step-by-Step
      Study. Ann Behav Med 2009;38:137-46); Ornes and Ransdell (A pilot study examining
      exercise self-efficacy as a mediator for walking behavior in college-age women.
      Perceptual Motor Skills, 2010;1101098-104)]. Taken together, prior studies
      suggest that ongoing research attention is warranted. Walking behaviour change
      intervention studies were searched using key search words 'walking promotion' and
      'pedometer' in the PubMed database. Initially, 87 articles were found and 25
      walking behaviour change interventions were reviewed to focus attention on
      reported theory use. Results of the review suggest that interventions that are
      theoretically underpinned may be no more effective than their counterparts. The
      Transtheoretical Model (TTM) and Social Cognitive Models were most frequently
      reported with positive effects noted for TTM use. The review also indicates that
      using single theory may be better than using multiple theories in a single
      intervention.

PMID- 29452363
TI  - StructureMapper: a high-throughput algorithm for analyzing protein sequence
      locations in structural data.
AB  - Motivation: StructureMapper is a high-throughput algorithm for automated mapping
      of protein primary amino sequence locations to existing three-dimensional protein
      structures. The algorithm is intended for facilitating easy and efficient
      utilization of structural information in protein characterization and proteomics.
      StructureMapper provides an analysis of the identified structural locations that
      includes surface accessibility, flexibility, protein-protein interfacing,
      intrinsic disorder prediction, secondary structure assignment, biological
      assembly information and sequence identity percentages, among other metrics.
      Results: We have showcased the use of the algorithm by estimating the coverage of
      structural information of the human proteome, identifying critical interface
      residues in DNA polymerase gamma, profiling structurally protease cleavage sites
      and post-translational modification sites, and by identifying putative, novel
      phosphoswitches. Availability and implementation: The StructureMapper algorithm
      is available as an online service and standalone implementation at
      http://structuremapper.uta.fi. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29452364
TI  - 4-Phenylbutyrate suppresses the unfolded protein response without restoring
      protein folding in Saccharomyces cerevisiae.
AB  - Accumulation of unfolded secretory proteins in the endoplasmic reticulum (ER),
      namely ER stress, is hazardous to eukaryotic cells and promotes the unfolded
      protein response (UPR). Ire1 is an ER-located transmembrane protein that senses
      ER stress and triggers the UPR. According to previous in vitro experiments, 4
      phenylbutyrate (4-PBA) works as a chemical molecular chaperone. Since 4-PBA
      attenuates the UPR in mammalian tissue cultures, this chemical may have clinical
      potential for restoring ER-stressing conditions. In this study, we investigated 4
      PBA's mode of action using the yeast Saccharomyces cerevisiae as a model
      organism. Although 4-PBA blocked a dithiothreitol (DTT)-induced UPR, it did not
      appear to restore impairment of ER protein folding that was caused by DTT.
      Moreover, even under non-stress conditions, 4-PBA attenuated UPR that was induced
      by an Ire1 mutant that exhibits a substantial activity without sensing ER
      accumulation of unfolded proteins. We also found that 4-PBA drastically promotes
      the degradation of Ire1. These observations indicate that at least in the case of
      yeast cells, 4-PBA suppresses the UPR not through restoration of the ER function
      to correctly fold proteins. Instead, the accelerated degradation of Ire1 possibly
      explains the reason why the UPR is attenuated by 4-PBA.

PMID- 29452365
TI  - Indigenous medicine and biomedical health care in fragile settings: insights from
      Burundi.
AB  - This study contributes to the health policy debate on medical systems integration
      by describing and analysing the interactions between health-care users,
      indigenous healers, and the biomedical public health system, in the so far rarely
      documented case of post-conflict Burundi. We adopt a mixed-methods approach
      combining (1) data from an existing survey on access to health-care, with 6,690
      individuals, and (2) original interviews and focus groups conducted in 2014 with
      121 respondents, including indigenous healers, biomedical staff, and health-care
      users. The findings reveal pluralistic patterns of health-care seeking behaviour,
      which are not primarily based on economic convenience or level of education.
      Indigenous healers' diagnosis is shown to revolve around the concept of 'enemy'
      and the need for protection against it. We suggest ways in which this category
      may intersect with the widespread experience of trauma following the civil
      conflict. Finally, we find that, while biomedical staff displays ambivalent
      attitudes towards healers, cross-referrals occasionally take place between
      healers and health centres. These findings are interpreted in light of the debate
      on health systems integration in Sub-Saharan Africa. In particular, we discuss
      policy options regarding healers' accreditation, technical training, management
      of cross-referrals as well as of herb-drug interactions; and we emphasise
      healers' psychological support role in helping communities deal with trauma. In
      this respect, we argue that the experience of conflict, and the experiences and
      conceptualizations of mental and physical illness, need to be taken into account
      when devising appropriate public or international health policy responses.

PMID- 29452366
TI  - Prevalence and Incidence of Anal and Cervical High-Risk Human Papillomavirus
      (HPV) Types Covered by Current HPV Vaccines Among HIV-Infected Women in the SUN
      Study.
AB  - Background: Nonavalent (9v) human papilloma virus vaccine targets high-risk human
      papillomavirus (HR-HPV) types 16, 18, 31, 33, 45, 52, 58, and low-risk 6, 11. We
      examined prevalence, incidence, and clearance of anal and cervical HR-HPV in HIV
      infected women. Methods: The SUN Study enrolled 167 US women in 2004-2006. Anal
      and cervical specimens were collected annually for cytology and identification of
      37 HPV types: 14 HR included: 9v 16, 18, 31, 33, 45, 52, 58; non-9v 35, 39, 51,
      56, 59, 66, 68. Results: Baseline characteristics of 126 women included: median
      age 38 years; 57% non-Hispanic black; 67% HIV RNA < 400 copies/mL; 90% CD4 counts
      >=200 cells/mm3. HPV prevalence at anus and cervix was 90% and 83%; for 9v HR-HPV
      types, 67% and 51%; non-9v HR-HPV, 54% and 29%, respectively. The 9v and non-9v
      HR-HPV incidence rates/100 person-years were similar (10.4 vs 9.5; 8.5 vs 8.3,
      respectively); 9v clearance rates were 42% and 61%; non-9v 46% and 59%, in anus
      and cervix, respectively. Conclusions: Anal HR-HPV prevalence was higher than
      cervical, with lower clearance; incidence was similar. Although prevalence of non
      9v HR-HPV was substantial, 9v HR-HPV types were generally more prevalent. These
      findings support use of nonavalent vaccine in HIV-infected women.

PMID- 29452367
TI  - Variant in human POFUT1 reduces enzymatic activity and likely causes a recessive
      microcephaly, global developmental delay with cardiac and vascular features.
AB  - Protein O-fucosyltransferase-1 (POFUT1) adds O-fucose monosaccharides to
      epidermal growth factor-like (EGF) repeats found on approximately 100 mammalian
      proteins, including Notch receptors. Haploinsufficiency of POFUT1 has been linked
      to adult-onset Dowling Degos Disease (DDD) with hyperpigmentation defects.
      Homozygous deletion of mouse Pofut1 results in embryonic lethality with severe
      Notch-like phenotypes including defects in somitogenesis, cardiogenesis,
      vasculogenesis and neurogenesis, but the extent to which POFUT1 is required for
      normal human development is not yet understood. Here we report a patient with a
      congenital syndrome consisting of severe global developmental delay,
      microcephaly, heart defects, failure to thrive and liver disease with a
      previously unreported homozygous NM_015352.1: c.485C>T variant (p.Ser162Leu) in
      POFUT1 detected by exome sequencing. Both parents are heterozygotes and neither
      manifests any signs of DDD. No other detected variant explained the phenotype.
      This variant eliminated a conserved N-glycosylation sequon at Asn160 in POFUT1
      and profoundly decreased POFUT1 activity in patient fibroblasts compared to
      control fibroblasts. Purified p.Ser162Leu mutant protein also showed much lower
      POFUT1 activity with a lower affinity for EGF acceptor substrate than wild type
      POFUT1. Eliminating the N-glycan sequon by replacing Asn160 with Gln had little
      effect on POFUT1 activity, suggesting that loss of the glycan is not responsible
      for the defect. Furthermore, the p.Ser162Leu mutant showed weaker ability to
      rescue Notch activity in cell-based assays. These results suggest that this N
      glycan of POFUT1 is not required for its proper enzymatic function, and that the
      p.Ser162Leu mutation of POFUT1 likely causes global developmental delay,
      microcephaly with vascular and cardiac defects.

PMID- 29452368
TI  - Validity of the Swedish Cardiac Surgery Registry.
AB  - OBJECTIVES: Our goal was to validate the Swedish Cardiac Surgery Registry by
      reviewing the reported cardiac operations to assess the completeness and quality
      of the registered data and the EuroSCORE II variables. METHODS: A total of 5837
      cardiac operations were reported to the Swedish Cardiac Surgery Registry in
      Sweden during 2015. A randomly selected sample of 753 patient records (13%) was
      scrutinized by 3 surgeons at all 8 units in Sweden performing open cardiac
      surgery in adults. RESULTS: Coverage was excellent with 99% [95% confidence
      interval (CI) 98-99%] of the performed procedures found in the registry. Reported
      waiting times for surgery were correct in 78% (95% CI 76-79%) of the cases. The
      main procedural code was correctly reported in 96% (95% CI 95-97%) of the cases.
      The correlation between reported and monitored logistic EuroSCORE II had a
      coefficient of 0.79 (95% CI 0.76-0.82), and the median difference in EuroSCORE II
      was 0% (interquartile range -0.4% to 0.4%). The majority of EuroSCORE II
      variables had good agreement and coherence; however, New York Heart Association
      functional class, preoperative renal dysfunction, left ventricular ejection
      fraction, Canadian Cardiovascular Society Class IV angina and poor mobility were
      less robust. Postoperative complications were rare and in general had a high
      degree of completeness and agreement. CONCLUSIONS: The reliability of the
      variables in the national Swedish Cardiac Surgery Registry was excellent. Thus,
      the registry is a valuable source of data for quality studies and research. Some
      EuroSCORE II variables require improved and stricter definitions to obtain
      uniform reporting and high validity.

PMID- 29452369
TI  - In search of the best xenogeneic material for a paediatric conduit: an analysis
      of clinical data.
AB  - OBJECTIVES: In this study, we aimed to determine the incidence of reintervention
      and calcification of xenografts in paediatric patients who underwent placement of
      the right ventricle-to-pulmonary artery valved conduits. METHODS: We
      retrospectively analysed clinical data of paediatric patients (1 day-18 years)
      who underwent right ventricular outflow tract reconstruction using xenograft from
      2000 to 2016 at a single centre. RESULTS: A total of 301 patients underwent the
      placement of 337 xenografts, including glutaraldehyde-treated bovine jugular vein
      (n = 171, 50.7%), glutaraldehyde-treated bovine pericardial valved conduit (n =
      75, 22.3%), diepoxy-treated porcine aortic conduit (n = 58, 17.2%) and diepoxy
      treated bovine pericardial valved conduit (DE-PVC) (n = 33, 9.8%). There were 284
      (84.3%) primary implantations and 53 (15.7%) reimplantations. The median follow
      up was 4.2 years (range 1.5 months-14.5 years). The multivariate regression
      analysis did not reveal statistically significant associations of the first
      reintervention with the type of xenograft (P = 0.78). At reintervention,
      calcification of the wall and/or cusps was the main cause of conduit dysfunction
      in 66.4% of cases. On the basis of the multivariate Cox regression analysis,
      xenograft types were significant predictors of reintervention caused by conduit
      calcification (P = 0.012). The diepoxy-treated porcine aortic conduit group had
      the risk of calcification 3 times higher than the glutaraldehyde-treated bovine
      jugular vein group (P < 0.001).The glutaraldehyde-treated bovine pericardial
      valved conduit and diepoxy-treated bovine pericardial valved conduit groups had
      the risk of calcification comparable with the glutaraldehyde-treated bovine
      jugular vein group in multivariate proportional hazards model (P = 0.36 and P =
      0.59, respectively). CONCLUSIONS: We have not revealed significant difference in
      the freedom from first reintervention among types of conduit. Calcification
      leading to the conduit dysfunction was present in all groups; however, diepoxy
      treated porcine aortic conduits demonstrated suboptimal results in terms of
      calcification at follow-up.

PMID- 29452370
TI  - Blood cardioplegia for cardiac surgery in acute myocardial infarction: rat
      experiments with two widely used solutions.
AB  - OBJECTIVES: Blood cardioplegia (BCP) can be used in different ways to protect the
      heart from ischaemia-reperfusion injury during cardiac surgery. Because there
      could be differences between warm and cold intermittent cardioplegia with or
      without warm reperfusion, we investigated the influence of 2 blood cardioplegia
      solutions on cardiac function, metabolism and infarct size in stable and
      infarcted rat hearts. METHODS: The hearts of 32 male Wistar rats were excised and
      inserted into a blood-perfused isolated heart apparatus. In 16 hearts, an acute
      myocardial infarction was induced by ligation of the left anterior descending
      coronary artery at least 30 min before aortic clamping. After aortic clamping,
      either Calafiore or Buckberg BCP was administered. During reperfusion, coronary
      blood flow, left ventricular developed pressure and dp/dt max were recorded, and
      oxygen consumption and lactate production were determined. The infarct size after
      90 min of reperfusion was measured by triphenyl tetrazolium chloride staining.
      The hearts of rats without infarction were investigated using transmission
      electron microscopy. RESULTS: In hearts without infarction, haemodynamic recovery
      was similar for Calafiore and Buckberg solutions: left ventricular developed
      pressure [Cala 62% of baseline (BL), Buck 58% BL] and dp/dt max (Cala 83% BL,
      Buck 89% BL). Coronary flow, which was slightly less in infarcted hearts, also
      recovered similarly after the administration of the 2 BCP solutions (Cala 65% BL,
      Buck 68% BL). During reperfusion, lactate production was similar (Cala 0.85
      ml/min, Buck 1.0 ml/min), and the cellular oedema index and mitochondrial
      swelling were comparable between the 2 groups. In hearts with infarction, left
      ventricular developed pressure (Cala 58% BL, Buck 56% BL) and dp/dt max (Cala 79%
      BL, Buck 72% BL) showed similar recovery for reperfusion with Calafiore or
      Buckberg BCP. In addition, coronary flow recovered similarly (Cala 54% BL, Buck
      57% BL). During reperfusion, myocardial oxygen consumption was lower in the Cala
      (67% BL) than in the Buck (82% BL) group, but lactate production was similar
      between the Cala (1.1 ml/min) and the Buck (1.1 ml/min) groups. Myocardial
      infarct size was also similar in the Cala group (24%) and in the Buck group
      (26%). CONCLUSIONS: In stable perfused rat hearts and in an in vitro model of
      acute myocardial infarction, the 2 BCP solutions offer equally good myocardial
      protection.

PMID- 29452371
TI  - A bidirectional association between cognitive ability in young adulthood and
      epilepsy: a population-based cohort study.
AB  - Aim: To investigate the bidirectional association between cognitive ability in
      young adulthood and epilepsy. Methods: This cohort study included 1 159 076 men
      enrolled in the mandatory conscription board examination from the Danish
      Conscription Database (DCD; 658 465 men examined 1957-84), the Danish Defence
      Personnel Organization Database (DPOD; 216 509 men examined 1987-2005) and the
      Danish Conscription Registry (DCR; 284 102 men examined 2006-15). A supplementary
      analysis included 14 814 female volunteers. Cognitive ability was measured at
      conscription, and epilepsy was ascertained by physician diagnoses in the Danish
      National Patient Registries 1977-2016 [using International Classification of
      Diseases (ICD) codes: ICD-8-345; ICD-10-G40-G41]. Differences in cognitive
      ability in relation to epilepsy status at the time of conscription (age 19) were
      calculated using linear regression. The risk of epilepsy associated with
      cognitive ability was estimated using Cox regression models, split at age at
      follow-up (40 and 60 years) and adjusted for year of birth, cerebrovascular
      disease, traumatic brain injury and education. Results: In all, 5097 (1.0%) men
      from the DPOD and DCR were diagnosed with epilepsy before conscription, and they
      had about 0.25 standard deviation (SD) lower cognitive scores than men without
      epilepsy. The largest difference in cognition was seen for those with the largest
      number of hospital contacts. A total of 22 364 (1.9%) men developed epilepsy, and
      cognitive ability was inversely associated with the risk of epilepsy. With the
      end of follow-up at age 40 years, the adjusted hazard ratio (HR)per SD increase
      was 0.75 (95% confidence interval = 0.73-0.77). The association attenuated with
      increasing age at diagnosis. The findings were replicated in female conscripts.
      Conclusions: The cognitive impairment seen in adults with epilepsy seems to
      reflect combined effects of epileptic processes and lower premorbid cognitive
      ability.

PMID- 29452372
TI  - Impact of Timing of Influenza Vaccination in Pregnancy on Transplacental Antibody
      Transfer, Influenza Incidence, and Birth Outcomes: A Randomized Trial in Rural
      Nepal.
AB  - Background: Maternal influenza vaccination protects mothers and their infants in
      low resource settings, but little is known about whether the protection varies by
      gestational age at vaccination. Methods: Women of childbearing age in rural
      southern Nepal were surveilled for pregnancy, consented and randomized to receive
      maternal influenza vaccination or placebo, with randomization stratified on
      gestational age (17-25 or 26-34 weeks). Enrollment occurred in 2 annual cohorts,
      and vaccinations occurred from April 2011 through September 2013. Results: In
      sum, 3693 women consented and enrolled, resulting in 3646 live births. Although
      cord blood antibody titers and the rise in maternal titers were generally greater
      when women were vaccinated later in pregnancy, this was not statistically
      significant. The incidence risk ratio (IRR) for maternal influenza in pregnancy
      through 6 months postpartum was 0.62 (95% confidence interval [CI]: 0.35, 1.10)
      for those vaccinated 17-25 weeks gestation and 0.89 (95% CI: 0.39, 2.00) for
      those 26-34 weeks. Infant influenza IRRs were 0.73 (95% CI: 0.51, 1.05) for those
      whose mothers were vaccinated earlier in gestation, and 0.63 (95% CI: 0.37, 1.08)
      for those later. Relative risks (RR) for low birthweight were 0.83 (95% CI: 0.71,
      0.98) and 0.90 (95% CI: 0.72, 1.12) for 17-25 and 26-34 weeks gestation at
      vaccination, respectively. IRRs did not differ for small-for-gestational age or
      preterm. No RRs were statistically different by timing of vaccine receipt.
      Conclusions: Vaccine efficacy did not vary by gestational age at vaccination,
      making maternal influenza immunization programs easier to implement where women
      present for care late in pregnancy. Clinical Trials Registration: NCT01034254.

PMID- 29452373
TI  - Corrigendum.

PMID- 29452374
TI  - Response to "The Importance of Clinically Relevant Research When Making
      Comparisons".

PMID- 29452375
TI  - 1alpha-Hydroxycholecalciferol improves the growth performance and up-regulates
      the mRNA expression of vitamin D receptor in the small intestine and kidney of
      broiler chickens.
AB  - 1alpha-Hydroxycholecalciferol (1alpha-OH-D3) is a vitamin D derivative. The
      objective of this study was to evaluate the effects of 1alpha-OH-D3 on the growth
      and the mRNA expression of vitamin D receptor (VDR) in the small intestine and
      kidney of chickens. A total of 240 males of one-day-old Ross 308 broilers was
      randomly assigned to 4 treatments with 5 replicates of 12 birds per replicate.
      Three levels of 1alpha-OH-D3 (1.25, 2.5, and 5 MUg/kg) were added to a basal diet
      containing 0.50% calcium (Ca), 0.25% non-phytate phosphorus (NPP), and without
      supplemental cholecalciferol (vitamin D3). The control diet contained 1.00% Ca,
      0.45% NPP, and 25 MUg/kg cholecalciferol. Dietary 1alpha-OH-D3 levels linearly
      improved the average daily feed intake (ADFI), average daily gain (ADG), femur
      and tibia mineralization, and plasma Ca concentration, and retained Ca and total
      phosphorus (tP) amounts in broilers from 1 to 21 d of age (P < 0.05). In
      addition, 1alpha-OH-D3 also linearly up-regulated the mRNA expression levels of
      VDR in the duodenum as well as those of VDR and sodium-phosphate cotransporter
      NaPi-IIa and NaPi-IIc in the kidney of broilers (P < 0.05). However, 1alpha-OH-D3
      did not affect the mRNA levels of 25-hydroxylase in the liver or NaPi-IIb in the
      duodenum (P > 0.05). No differences were observed in the ADFI, ADG, bone length,
      plasma mineral concentration, retained tP amount, or the mRNA levels of the above
      genes (except for VDR in the kidney) between the birds fed the diet with 5 MUg/kg
      1alpha-OH-D3 and the birds fed the control diet (P > 0.05). By contrast, the
      weight, ash weight, ash percentage, and Ca percentage of the bone, retained Ca
      amount, and the mRNA level of VDR in the kidney were lower in the birds fed the
      diet with 5 MUg/kg 1alpha-OH-D3 than in the birds fed the control diet (P <
      0.05). These data indicate that 1alpha-OH-D3 up-regulates the gene expression of
      VDR in the small intestine and kidney at the transcriptional level, thereby
      improving the growth performance and bone mineralization of broiler chickens from
      1 to 21 d of age.

PMID- 29452376
TI  - The Vacuolar Transportome of Plant Specialized Metabolites.
AB  - The plant vacuole is a cellular compartment that is essential to plant
      development and growth. Often plant vacuoles accumulate specialized metabolites,
      also called secondary metabolites, which constitute functionally and chemically
      diverse compounds that exert in planta many essential functions and improve the
      plant's fitness. These metabolites provide, for example, chemical defense against
      herbivorous and pathogens or chemical attractants (color and fragrance) to
      attract pollinators. The chemical composition of the vacuole is dynamic, and is
      altered during development and as a response to environmental changes. To some
      extent these alterations rely on vacuolar transporters, which import and export
      compounds into and out of the vacuole, respectively. During the past decade,
      significant progress was made in the identification and functional
      characterization of the transporters implicated in many aspects of plant
      specialized metabolism. Still, deciphering the molecular players underlying such
      processes remains a challenge for the future. In this review, we present a
      comprehensive summary of the most recent achievements in this field.

PMID- 29452378
TI  - Patients Maintained on Buprenorphine for Opioid Use Disorder Should Continue
      Buprenorphine Through the Perioperative Period.

PMID- 29452377
TI  - Discordance in the Dependence on Kisspeptin Signaling in Mini Puberty vs
      Adolescent Puberty: Human Genetic Evidence.
AB  - Context: Hypothalamic kisspeptin signaling plays a critical role in the
      initiation and maintenance of reproductive function. Biallelic mutations in the
      coding sequence of KISS1R (GPR54) have been identified in patients with
      idiopathic hypogonadotropic hypogonadism, but it is unknown whether biallelic
      variants can also be associated with related reproductive disorders. Case
      Description: A missense homozygous variant (c.890G>T p.R297L) in KISS1R was
      identified in a child who presented with microphallus and bilateral
      cryptorchidism. This variant has been reported to reduce, but not abolish,
      postreceptor signaling in vitro. Biochemical evaluation during the neonatal
      period revealed low testosterone levels. By 11 years and 8 months, the boy began
      demonstrating increases in testicular volume. By 17 years and 3 months, his
      testicular volume was 20 mL; his penile length was 7.3 cm; and he had adult
      levels of circulating gonadotropins and testosterone. Conclusion: This case
      report associates biallelic loss-of-function mutations in KISS1R with normal
      timing of adolescent puberty. Because these coding sequence variants occurred in
      a patient with microphallus and cryptorchidism, they demonstrate different levels
      of dependence of the hypothalamic-pituitary-gonadal cascade on kisspeptin
      signaling at distinct times in the reproductive life span. The suppression of the
      hypothalamic-pituitary-gonadal cascade during early life but not adolescence
      suggests that the mini puberty of infancy depends more on kisspeptin-induced,
      gonadotropin-releasing hormone-induced luteinizing hormone secretion than does
      adolescent puberty.

PMID- 29452379
TI  - Reply to San Giorgi and Dikkers.

PMID- 29452381
TI  - A fungal Argonaute interferes with RNA interference.

PMID- 29452380
TI  - Relative Vaccine Effectiveness of High-Dose Versus Standard-Dose Influenza
      Vaccines Among Veterans Health Administration Patients.
AB  - Background: We examined whether a high-dose inactivated influenza vaccine was
      more efficacious in preventing hospitalizations than a standard-dose vaccine in
      the Veterans Health Administration (VHA) senior population. Methods: This study
      estimated the relative vaccine effectiveness (rVE) of high dose versus standard
      dose using a retrospective cohort of VHA patients 65 years of age or older in the
      2015-2016 influenza season. To adjust for measured confounders, we matched each
      high-dose recipient with up to 4 standard-dose recipients vaccinated at the same
      location within a 2-week period and having 2 or more pre-existing medical
      comorbidities. We used the previous event rate ratio method (PERR), a type of
      difference-in-differences analysis, to adjust for unmeasured confounders.
      Results: We evaluated 104965 standard-dose and 125776 high-dose recipients;
      matching decreased the population to 49091 standard-dose and 24682 high-dose
      recipients. The matched, PERR-adjusted rVE was 25% (95% confidence interval [CI],
      2%-43%) against influenza- or pneumonia-associated hospitalization, 7% (95% CI, 
      2% to 14%) against all-cause hospitalization, 14% (95% CI, -8% to 32%) against
      influenza- or pneumonia-associated outpatient visit, 5% (95% CI, 2%-8%) against
      all-cause outpatient visit, and 38% (95% CI, -5% to 65%) against laboratory
      confirmed influenza. Conclusions: In protecting senior VHA patients against
      influenza- or pneumonia-associated hospitalization, a high-dose influenza vaccine
      is more effective than a standard-dose vaccine.

PMID- 29452382
TI  - Simulated ablation for detection of cells impacting paracrine signalling in
      histology analysis.
AB  - Intra-tumour phenotypic heterogeneity limits accuracy of clinical diagnostics and
      hampers the efficiency of anti-cancer therapies. Dealing with this cellular
      heterogeneity requires adequate understanding of its sources, which is extremely
      difficult, as phenotypes of tumour cells integrate hardwired (epi)mutational
      differences with the dynamic responses to microenvironmental cues. The later
      comes in form of both direct physical interactions, as well as inputs from
      gradients of secreted signalling molecules. Furthermore, tumour cells can not
      only receive microenvironmental cues, but also produce them. Despite high
      biological and clinical importance of understanding spatial aspects of paracrine
      signaling, adequate research tools are largely lacking. Here, a partial
      differential equation (PDE)-based mathematical model is developed that mimics the
      process of cell ablation. This model suggests how each cell might contribute to
      the microenvironment by either absorbing or secreting diffusible factors, and
      quantifies the extent to which observed intensities can be explained via
      diffusion-mediated signalling. The model allows for the separation of phenotypic
      responses to signalling gradients within tumour microenvironments from the
      combined influence of responses mediated by direct physical contact and hardwired
      (epi)genetic differences. The method is applied to a multi-channel
      immunofluorescence in situ hybridisation (iFISH)-stained breast cancer
      histological specimen, and correlations are investigated between: HER2 gene
      amplification, HER2 protein expression and cell interaction with the diffusible
      microenvironment. This approach allows partial deconvolution of the complex
      inputs that shape phenotypic heterogeneity of tumour cells and identifies cells
      that significantly impact gradients of signalling molecules.

PMID- 29452383
TI  - The Effectiveness of Asian Bush Mosquito (Aedes japonicus japonicus) Control
      Actions in Colonised Peri-urban Areas in the Netherlands.
AB  - The Asian bush mosquito (Aedes japonicus japonicus (Theobald)) is an invasive
      mosquito species in Europe. In 2012, it was for the first time detected in the
      Netherlands, in the municipality of Lelystad. After further research, thousands
      of specimens were found in the surrounding peri-urban areas of the city. A
      targeted mosquito control campaign began in 2015 with the objective of reducing
      populations in locations with the highest concentrations of Ae. japonicus
      breeding sites: allotment garden complexes. Mosquito control consisted of source
      reduction combined with application of the larvicide Vectomax in breeding sites.
      At eight complexes, mosquito control effectiveness has been systematically
      measured by sampling larvae from breeding sites. Six measurements were performed
      between 2015 and 2016. Results show that the effectiveness of mosquito control
      actions was similar in all treated allotment gardens and resulted in a
      significant reduction in Ae. japonicus larval abundance. Rain barrels at the
      allotments represent the most frequent breeding site in Lelystad, but every water
      filled artificial container is a potential breeding site for the species. Ae.
      japonicus was not found in the samples taken in other allotment gardens in the
      province of Flevoland; however, the collection methodology used proven to be
      effective in detecting this species when it has newly colonized surrounding
      areas. Targeted mosquito control actions at the breeding sites are crucial for
      successful reduction of populations of an invasive mosquito species, and
      systematic measurements of the effectiveness, is in this case, the base to
      understand the dynamics of Ae. japonicus populations after mosquito control.

PMID- 29452384
TI  - Response.

PMID- 29452385
TI  - Longitudinal Tobacco Use Transitions Among Adolescents and Young Adults: 2014
      2016.
AB  - Introduction: Among youth, the frequency and prevalence of using more than one
      tobacco (small cigar, cigarette, and hookah) or nicotine-containing product (e
      cigarettes-ENDS) are changing. These shifts pose challenges for regulation,
      intervention, and prevention campaigns because of scant longitudinal data on the
      stability of use patterns in this changing product landscape. Methods: A
      nationally representative longitudinal survey of 15- to 21-year olds (n = 15,275)
      was used to describe transitions between never use, noncurrent use, and past 30
      day use of combustible tobacco, e-cigarettes (ENDS), and dual use of both kinds
      of products. A multistate model was fit to observations collected every 6 months
      across 2.5 years to estimate the probability of transitions between states (TPs),
      the average time in state (sojourn time), and the effect of age on transitions.
      Results: Current state strongly predicted future state over time intervals of 1
      year or less, but only weakly predicted future state at longer intervals: TP to
      noncurrent use was higher for ENDS-only than combustible-only users over a 6
      month interval but was similar for both groups over a 2-year interval. Sojourn
      time was significantly longer for combustible-only (0.52 years) and dual use
      (0.55 years) than ENDS-only use (0.27 years); older youth were more likely than
      younger youth to stay combustible tobacco users or noncurrent users. Conclusions:
      The dynamics of transitions between combustible tobacco products and ENDS in a
      population of youth and young adults suggest that policy and prevention efforts
      must consider the frequent changes and instability over a 1-year or less time
      period in use patterns among young people. Implications: The study addresses an
      urgent need in public health for timely information on how youth and young adults
      use tobacco and nicotine products. We found that youth, particularly adolescents,
      moved frequently between using ENDS and combustible tobacco products either alone
      or together. Importantly, the utility of current-use states for predicting future
      use states declined for time horizons longer than 1 year. Our results demonstrate
      a need for caution in interpreting product transitions. Longitudinal data with
      frequent observations and coverage of a wide range of possible product types is
      required to fully characterize usage patterns in youth.

PMID- 29452386
TI  - Amino acid digestibility of larval meal (Musca domestica) for broiler chickens.
AB  - Work was undertaken to investigate the potential use of housefly (Musca
      domestica) larvae reared on broiler manure as a source of nutrition for poultry
      production in the United Kingdom. Nutritional analysis showed that larvae have a
      high (>45% dry wt.) protein content and a favorable amino acid profile that is
      rich in key amino acids, such as lysine and methionine. A broiler digestibility
      trial was carried out to determine the apparent ileal digestibility coefficients
      (AIDC) and true ileal digestibility coefficients (TIDC) of amino acids (AA) from
      insect larval meal (ILM) from M. domestica and fishmeal (FM) in broiler chickens.
      This was calculated using multiple linear regression technique based upon 3
      inclusions of each protein source in a semisynthetic diet. One-hundred-forty-four
      day-old male (Ross 308) broilers were fed from hatch on a commercial starter diet
      for 20 days. Experimental diets were fed from d 21 to 28, and feed intakes were
      measured daily. On d 28, the trial was terminated, ileal digesta were collected
      for the determination of AIDC and TIDC of AA, and inflammatory responses (gizzard
      erosion and eye discharge) were measured. No significant differences were
      observed in digestibilities between protein sources for any AA. Furthermore, ILM
      feeding did not induce gizzard erosion or eye discharge at any inclusion. These
      results provide strong evidence to suggest that ILM of the common housefly can
      provide a successful alternative protein source to FM in broiler diets.

PMID- 29452387
TI  - OAS1, 2, and 3: Significance During Active Tuberculosis?
AB  - Evidence to-date points to a detrimental role of the type I IFNs during
      tuberculosis. The mechanisms underpinning the IFNalphabeta-mediated exacerbation
      of the disease is unclear. The 2'-5'-oligoadenylate synthetases (OAS), namely
      OAS1, OAS2 and OAS3 are part of the interferon-induced genes which until now have
      been synonymous with an anti-viral function. Blood transcriptome profiling has
      continuously observed their upregulation in a number of gene expression
      signatures which discriminate active TB from latent TB infection, however the
      role of the OASs and the effect that their expression has on the pathogenesis and
      persistence of TB is unknown. Evidence suggests that the OASs exhibit other
      cellular functions which include the induction of apoptosis, enhancement of
      IFNalphabeta signalling, immune cell receptor modulation and autophagy. We
      propose that i) during the late stages of disease, sustained RNaseL expression
      through OAS activation enhances type I IFN signalling and, ii) that they may
      exhibit immune-modulatory capabilities.

PMID- 29452388
TI  - Structural and functional changes in coffee trees after 4 years under free air
      CO2 enrichment.
AB  - Background and Aims: Climate forecasts suggest that [CO2] in the atmosphere will
      continue to increase. Structural and ecophysiological responses to elevated air
      [CO2] (e[CO2]) in tree species are contradictory due to species-dependent
      responses and relatively short-term experiments. It was hypothesized that long
      term exposure (4 year) to e[CO2] would change canopy structure and function of
      Coffea arabica trees. Methods: Coffee plants were grown in a FACE (free air CO2
      enrichment) facility under two air [CO2]: actual and elevated (actual + approx.
      200 MUL CO2 L-1). Plants were codified following the VPlants methodology to
      obtain coffee mock-ups. Plant canopies were separated into three 50 cm thick
      layers over a vertical profile to evaluate their structure and photosynthesis,
      using functional-structural plant modelling. Key Results: Leaf area was strongly
      reduced on the bottom and upper canopy layers, and increased soil carbon
      concentration suggested changes in carbon partitioning of coffee trees under
      e[CO2]. Increased air [CO2] stimulated stomatal conductance and leaf
      photosynthesis at the middle and upper canopy layers, increasing water-use
      efficiency. Under e[CO2], plants showed reduced diameter of the second-order axes
      and higher investment in the youngest third to fifth-order axes. Conclusions: The
      responses of Arabica coffee grown under long-term exposure to e[CO2] integrated
      structural and functional modifications, which balanced leaf area loss through
      improvements in leaf and whole-plant photosynthesis.

PMID- 29452389
TI  - Parity associated with telomere length among US reproductive age women.
AB  - STUDY QUESTION: Is telomere length related to parity among a nationally
      representative sample of US reproductive age women? SUMMARY ANSWER: History of
      live birth was associated with shorter telomere length. WHAT IS KNOWN ALREADY:
      Shorter telomeres have been linked with a range of chronic health conditions and
      mortality and parity has been associated with health indicators. However, there
      is a lack of research on how parity relates to telomere length. STUDY DESIGN,
      SIZE, DURATION: This nationally representative, cross-sectional study included
      1954 women from the National Health and Nutrition Examination Survey, 1999-2002,
      the only survey period which includes measurement of telomere length.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 20-44 were included. Parity,
      defined as number of previous live births, was ascertained by questionnaire.
      Leukocyte telomere length was measured by polymerase chain reaction and reported
      as a ratio in relation to standard reference DNA (T/S ratio). The relationship
      between leukocyte T/S ratio and parity was examined using survey weighted linear
      regression. Models were adjusted for race/ethnicity, age, BMI, income-to-poverty
      ratio, education, early age at menarche and smoking status. MAIN RESULTS AND THE
      ROLE OF CHANCE: Among reproductive age women in the US, the adjusted mean
      leukocyte T/S ratio was 4.2% (95% CI: 0.9, 7.3) shorter in parous compared with
      nulliparous women. Parity was associated with 116 fewer base pairs (95% CI: 26,
      204) on average, using estimated coefficients from the adjusted linear regression
      models and mean covariate values. LIMITATIONS REASONS FOR CAUTION: This study was
      cross-sectional and therefore was unable to establish temporality. The dataset
      lacked information on social factors, stress and fertility status, which may help
      explain these findings. Only two previous studies have examined this question and
      our findings should be interpreted with caution. WIDER IMPLICATIONS OF THE
      FINDINGS: These findings in a nationally representative sample of US reproductive
      age women suggest that history of live birth may be associated with accelerated
      cellular aging. The magnitude of the observed association was greater than that
      of the impact of smoking or obesity on telomere length, suggesting that parity
      may have an independent influence on cellular aging and warrant further study.
      STUDY FUNDING/COMPETING INTEREST(S): The study was funded in part by the
      Undergraduate Research Scholars Program at George Mason University. The authors
      have no conflicts of interest. TRIAL REGISTRATION NUMBER: NA.

PMID- 29452390
TI  - Effects of storage conditions on hatchability, embryonic survival and
      cytoarchitectural properties in broiler from young and old flocks.
AB  - Storing eggs at low temperature prior to incubation is common practice in the
      broiler hatchery industry; however, prolonged storage (beyond 7 d) is known to
      increase early embryonic mortality and reduce chick quality and performance. To
      better understand the basis of this mortality, we previously published milestone
      criteria to evaluate morphological and cellular properties of the freshly laid
      embryo. Using these criteria, in the present study we checked the effects of
      storage at 18 degrees C and 12 degrees C for up to 28 d on hatchability and chick
      quality. Furthermore, using a 3D high-resolution episcopic microscopy (HREM)
      imaging system combined with standard and confocal microscopy and cell viability
      markers, we analyzed the effects of the different storage conditions on embryonic
      developmental stage, cytoarchitectural properties, mitotic index and cell
      survival. A total of 1,483 eggs from a young flock were divided in 2 groups, 18
      degrees C and 12 degrees C, and stored for 7, 14, 21, and 28 d. Following
      storage, randomly selected 1,222 eggs were incubated, and the hatched chicks were
      evaluated for chick quality parameters. Nonhatched eggs were also analyzed to
      determine the stage of embryonic mortality. The remaining 261 eggs were isolated
      and analyzed for developmental stage, cytoarchitecture, mitotic index, and cell
      death following storage. Hatchability rates beyond 7 d of storage at 12 degrees C
      were significantly improved compared to 18 degrees C, and chick quality remained
      high. Similar results were obtained for an old flock's eggs (n = 1,350).
      Analyzing the embryos, at each time point, we found that at 12 degrees C, the
      developmental progression during storage slows significantly, mitotic index-which
      at this temperature may indicate mitotic arrest-increases and the rate of early
      apoptosis is half than at 18 degrees C. Moreover, the HREM system and
      histological sections showed that embryos stored at 18 degrees C for prolonged
      times undergo dramatic cytoarchitectural changes that may be maladaptive to
      resuming normal development after diapause. We thus demonstrate the usefulness of
      the milestone criteria for predicting and studying the storage conditions that
      will allow for better performance in hatchery practice.

PMID- 29452391
TI  - Lithoplasty-assisted transfemoral aortic valve implantation.

PMID- 29452392
TI  - pBRIT: gene prioritization by correlating functional and phenotypic annotations
      through integrative data fusion.
AB  - Motivation: Computational gene prioritization can aid in disease gene
      identification. Here, we propose pBRIT (prioritization using Bayesian Ridge
      regression and Information Theoretic model), a novel adaptive and scalable
      prioritization tool, integrating Pubmed abstracts, Gene Ontology, Sequence
      similarities, Mammalian and Human Phenotype Ontology, Pathway, Interactions,
      Disease Ontology, Gene Association database and Human Genome Epidemiology
      database, into the prediction model. We explore and address effects of sparsity
      and inter-feature dependencies within annotation sources, and the impact of bias
      towards specific annotations. Results: pBRIT models feature dependencies and
      sparsity by an Information-Theoretic (data driven) approach and applies
      intermediate integration based data fusion. Following the hypothesis that genes
      underlying similar diseases will share functional and phenotype characteristics,
      it incorporates Bayesian Ridge regression to learn a linear mapping between
      functional and phenotype annotations. Genes are prioritized on phenotypic
      concordance to the training genes. We evaluated pBRIT against nine existing
      methods, and on over 2000 HPO-gene associations retrieved after construction of
      pBRIT data sources. We achieve maximum AUC scores ranging from 0.92 to 0.96
      against benchmark datasets and of 0.80 against the time-stamped HPO entries,
      indicating good performance with high sensitivity and specificity. Our model
      shows stable performance with regard to changes in the underlying annotation
      data, is fast and scalable for implementation in routine pipelines. Availability
      and implementation: http://biomina.be/apps/pbrit/;
      https://bitbucket.org/medgenua/pbrit. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 29452393
TI  - No copper supplementation in a corn-soybean basal diet has no adverse effects on
      late-phase laying hens under normal and cyclic high temperatures.
AB  - Over supplementation of copper (Cu) in animal diets may cause serious pollution
      in soil, water and harvested crops. To minimize the potential pollution, the
      effects of corn-soybean basal diet with or without supplementation of 8 mg Cu/kg
      on laying performance, plasma biochemical metabolic indices, and antioxidant
      status in laying hens were evaluated under normal and cyclic high temperatures. A
      total of 240 Hy-Line Brown laying hens were randomly allotted to 4 treatments
      with 6 replicates of 10 hens per replicate according to factorial design involved
      in 2 temperatures [normal temperature (NT) vs. cyclic high temperature (CHT)] and
      2 dietary Cu addition amount [Cu0 (0 mg/kg) vs. Cu8 (8 mg/kg in the form of
      CuSO4.5H2O)]. The experimental period included 1-week adaptation, 2-week heat
      stress and 2-week convalescence. The temperatures of NT groups in the same period
      or any groups during other periods were kept at 26 +/- 2 degrees C except that of
      CHT groups were 26 +/- 2 degrees C~33 +/- 2 degrees C cyclically during heat
      stress period. CHT groups increased (P < 0.05) the rectal temperature and plasma
      glucose content under heat stress, but decreased (P < 0.01) the egg yield at the
      second week of heat stress and the first week of convalescence, and the plasma
      triglyceride, uric acid, and triiodothyronine levels under heat stress. Cu8
      groups increased (P < 0.05) egg weight at the first week of convalescence, and
      plasma thyroxin level during the whole convalescence. Interactions between
      temperature and Cu content existed (P < 0.05) in the laying rate at the first
      week of convalescence, and the plasma lactic dehydrogenase level under heat
      stress. Conclusively, the CHT impaired laying performance. The Cu content (10.3
      mg/kg) in corn-soybean basal diet might be sufficient for meeting the maintenance
      and production requirements of late-phase laying hens, and no Cu supplementation
      had no adverse effects on egg production and antioxidant indices under cyclic
      high (26 +/- 2 degrees C~33 +/- 2 degrees C) or normal (26 +/- 2 degrees C)
      temperatures.

PMID- 29452394
TI  - Treatment of hypertrophic cardiomyopathy caused by cardiospecific variants of
      Fabry disease with chaperone therapy.

PMID- 29452395
TI  - Mini-extracorporeal circulation technology, conventional bypass and prime
      displacement in isolated coronary and aortic valve surgery: a propensity-matched
      in-hospital and survival analysis.
AB  - OBJECTIVES: Conventional cardiopulmonary bypass is the most commonly used means
      of artificial circulation in cardiac surgery. However, it suffers from the
      effects of haemodilution and activation of inflammatory/coagulation cascades.
      Prime displacement (PD) can offset haemodilution and mini-extracorporeal
      technology (MIECT) can offset both. So far, no study has compared all of these
      modalities together; hence, we compared the outcomes of these 3 modalities at our
      institution. METHODS: This was a retrospective analysis of our cardiac surgical
      database. A total of 9626 patients underwent conventional bypass (CB), 3125
      patients underwent a modification of CB, called PD, and 904 underwent MIECT. A
      1:1 propensity-matching algorithm was employed using IBM SPSS 24 to match (i) 813
      MIECT patients with 813 CB patients and (ii) 717 MIECT patients with 717 PD
      patients. The patients included coronary artery bypass grafting and valve
      surgery. RESULTS: MIECT had significantly (P < 0.05) longer bypass and cross
      clamp times compared to CB and PD. MIECT had significantly higher rates of
      postoperative atrial fibrillation associated with it compared to CB. The mean red
      cell blood transfusion was significantly lower in the MIECT group compared to the
      CB group as was the mean platelet transfusion and fresh frozen plasma
      transfusion. The overall 5-year survival was higher in the MIECT group compared
      to the CB group (log-rank, P = 0.018). Between the MIECT and the PD groups, we
      found the incidence of renal failure and gastrointestinal complications to be
      significantly higher in the PD group compared to the MIECT group. CONCLUSIONS:
      MIECT has short-term advantages over CB and PD. However, due to the retrospective
      limitations of the study, including calendar time bias, a multicentre randomized
      controlled trial comparing all 3 modalities will be beneficial for the larger
      cardiac community.

PMID- 29452396
TI  - Changes in access to primary care in Europe and its patterning, 2007-12: a
      repeated cross-sectional study.
AB  - Background: The strengthening of primary care (PC) has been encouraged as a
      strategy to achieve more efficient and equitable health systems. However, the
      Great Recession may have reduced access to PC. This paper analyses the change in
      access to PC and its patterning in 28 European countries between 2007 and 2012.
      Methods: We used data from the 2007 and 2012 waves of the EU-SILC questionnaire
      (n = 687 170). The dependent variable was the self-reported access to PC ('easy'
      vs. 'difficult'). We modelled the access to PC as a function of the year and
      individual socioeconomic and country-level health system variables, using a mixed
      effects logistic regression, adjusting for sex, age, civil status, country of
      birth, chronic condition and self-reported health. Additionally, we interacted
      the year with socioeconomic and country-level variables. Results: The probability
      of reporting difficult access to PC services was 4% lower in 2012, in comparison
      with 2007 (OR = 0.96, P < 0.01). People with the lowest educational level (OR =
      1.63, P < 0.01), high difficulty to make ends meet (OR = 1.94, P < 0.01) and with
      material deprivation (OR = 1.25, P < 0.01) experienced a significantly higher
      likelihood of difficult access. The better access in 2012 was significantly
      higher in people living in countries with higher health expenditures, a greater
      number of generalist medical practitioners, and with stronger gatekeeping.
      Conclusion: Access to PC improved between 2007 and 2012, and this improvement was
      greater for people living in countries with a higher investment in health and PC.
      However, the poor access amongst low-SE status people was stable over the period.

PMID- 29452397
TI  - Cohort Profile: The Singapore Multi-Ethnic Cohort (MEC) study.

PMID- 29452398
TI  - Predominant patterns of splicing evolution on human, chimpanzee and macaque
      evolutionary lineages.
AB  - Although splicing is widespread and evolves rapidly among species, the mechanisms
      driving this evolution, as well as its functional implications, are not yet fully
      understood. We analyzed the evolution of splicing patterns based on transcriptome
      data from five tissues of humans, chimpanzees, rhesus macaques and mice. In
      total, 1526 exons and exon sets from 1236 genes showed significant splicing
      differences among primates. More than 60% of these differences represent
      constitutive-to-alternative exon transitions while an additional 25% represent
      changes in exon inclusion frequency. These two dominant evolutionary patterns
      have contrasting conservation, regulation and functional features. The sum of
      these features indicates that, despite their prevalence, constitutive-to
      alternative exon transitions do not substantially contribute to long-term
      functional transcriptome changes. Conversely, changes in exon inclusion frequency
      appear to be functionally relevant, especially for changes taking place in the
      brain on the human evolutionary lineage.

PMID- 29452399
TI  - Response of goose intestinal microflora to the source and level of dietary fiber.
AB  - Geese are capable of digesting and making use of a high-fiber diet, but the
      mechanism is not well understood and would be of great significance for the
      development and utilization of roughage resources. In this study, we investigated
      the effect of dietary fiber (source: corn stover and alfalfa, included at 5% or
      8%) on microflora in goose intestines. We used 35-day-old Carlos geese in which
      we first studied the influence of fiber ingestion on diet digestibility and
      immune organ indices of geese and found that high dietary fiber (8% content)
      significantly increased feed intake, the digestibility of neutral and acid
      detergent fiber, and thymus, bursa, and spleen size. Subsequently, we
      investigated the effect of dietary fiber on the microbial flora in the various
      intestinal segments by high throughput sequencing. The bacterial diversity and
      relative abundance were significantly affected by the type and amount of dietary
      fiber fed, including that of cellulolytic bacteria such as Bacteroides,
      Ruminococcus, Clostridium, and Pseudomonas spp. Finally, we isolated and
      identified 8 strains with cellulolytic ability from goose intestine and then
      analyzed their activities in combination. The optimal combination for cellulase
      activity was Cerea bacillus and Pseudomonas aeruginosa. This study has laid a
      theoretical and practical foundation for knowledge of the efficient conversion
      and utilization of cellulose by geese.

PMID- 29452400
TI  - Sleep quality in well-defined Lyme disease: a clinical cohort study in Maryland.
AB  - Study Objectives: Lyme disease (LD) is the most common vector-borne disease in
      the United States. Approximately 5-15 per cent of patients develop postantibiotic
      treatment symptoms termed post-treatment Lyme disease syndrome (PTLDS). The
      primary objective of this study is to examine and quantify sleep quality among
      patients with early LD during the acute and convalescent periods, including among
      the subset who met criteria for PTLDS. Methods: This paper draws from a clinical
      cohort study of participants with early LD (n = 122) and a subcohort of
      individuals who later met criteria for PTLDS (n = 6). Participants were followed
      for 1 year after antibiotic treatment. The Pittsburgh Sleep Quality Index and
      standardized measures of pain, fatigue, depressive symptoms, and functional
      impact were administered at all visits for participants and controls (n = 26).
      Participants meeting criteria for PTLDS at 1 year post-treatment were compared
      with a subset of PSQI-defined poor sleeping controls (n = 10). Results: At the
      pretreatment visit, participants with early LD reported poorer sleep than
      controls. By 6 months post-treatment, participant sleep scores as a group
      returned to control levels. Participants with PTLDS reported significantly worse
      global sleep and sleep disturbance scores and worse fatigue, functional impact,
      and more cognitive-affective depressive symptoms compared with poor sleeping
      controls. Conclusions: Participants with early LD experienced poor sleep quality,
      which is associated with typical LD symptoms of pain and fatigue. In the subset
      of patients who developed PTLDS, sleep quality remains affected for up to 1 year
      post-treatment and is commonly associated with pain. Sleep quality should be
      considered in the clinical picture for LD and PTLDS.

PMID- 29452401
TI  - Understanding communication breakdown in the outpatient referral process in Latin
      America: a cross-sectional study on the use of clinical correspondence in public
      healthcare networks of six countries.
AB  - An adequate use of referral and reply letters-the main form of communication
      between primary care (PC) and out-patient secondary care (SC)-helps to avoid
      medical errors, test duplications and delays in diagnosis. However, it has been
      little studied to date in Latin America. The aim is to determine the level and
      characteristics of PC and SC doctors' use of referral and reply letters and to
      explore influencing factors in public healthcare networks of Argentina, Brazil,
      Chile, Colombia, Mexico and Uruguay. A cross-sectional study was conducted
      through a survey of PC and SC doctors working in public healthcare networks (348
      doctors per country). The COORDENA questionnaire was applied to measure the
      frequency of use and receipt of referral and reply letters, quality of contents,
      timeliness and difficulties in using them. Descriptive analyses were conducted
      and a multivariate logistic regression model was generated to assess the
      relationship between frequent use and associated factors. The great majority of
      doctors claim that they send referral letters to the other level. However, only
      half of SC doctors (a higher proportion in Chile and Mexico) report that they
      receive referral letters and <20% of PC doctors receive a reply from specialists.
      Insufficient recording of data is reported in terms of medical history, tests and
      medication and the reason for referral. The factor associated with frequent use
      of the referral letter is doctors' age, while the use of reply letters is
      associated with identifying PC doctors as care coordinators, knowing them and
      trusting in their clinical skills, and receiving referral letters. Significant
      problems are revealed in the use of referral and reply letters which may affect
      quality of care. Multifaceted strategies are required that foster a direct
      contact between doctors and a better understanding of the PC-based model.

PMID- 29452403
TI  - Mechanisms controlling nucleic acid-sensing Toll-like receptors.
AB  - Nucleic acid (NA)-sensing Toll-like receptors (TLRs) respond to DNA/RNA derived
      from pathogens and dead cells. Structural studies have revealed a variety of
      molecular mechanisms by which TLRs sense NAs. Double-stranded RNA and single
      stranded DNA directly bind to TLR3 and TLR9, respectively, whereas TLR7 and TLR8
      bind to nucleosides and oligoribonucleotides derived from RNAs. Activation of
      ligand-bound TLRs is influenced by the functional status of TLRs. Proteolytic
      cleavage of NA-sensing TLRs enables ligand-dependent TLR dimerization.
      Trafficking of ligand-activated TLRs in endosomal and lysosomal compartments is
      requisite for production of type I interferons. Activation of NA-sensing TLRs is
      required for the control of viruses such as herpes simplex virus and endogenous
      retroviruses. On the other hand, excessive activation of NA-sensing TLRs drives
      disease progression in a variety of inflammatory diseases including systemic
      lupus erythematosus, heart failure, arthritis and non-alcoholic steatohepatitis.
      NA-sensing TLRs are targets for therapeutic intervention in these diseases. We
      here focus on our recent progresses in our understanding of NA-sensing TLRs.

PMID- 29452402
TI  - Mitotane Monotherapy in Patients With Advanced Adrenocortical Carcinoma.
AB  - Context: Although mitotane is the only approved drug for the treatment of
      adrenocortical carcinoma (ACC), data on monotherapy in advanced disease are still
      scarce. Objective: To assess the efficacy of mitotane in advanced ACC in a
      contemporary setting and to identify predictive factors. Design and Setting:
      Multicenter cohort study of three German referral centers. Patients: One hundred
      twenty-seven patients with advanced ACC treated with mitotane monotherapy.
      Outcome Measures: Response Evaluation Criteria in Solid Tumors evaluation,
      progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier method,
      and predictive factors by Cox regression. Results: Twenty-six patients (20.5%)
      experienced objective response, including three with complete remission. Overall,
      median PFS was 4.1 months (range 1.0 to 73) and median OS 18.5 months (range 1.3
      to 220). Multivariate analysis indicated two main predictive factors: low tumor
      burden (<10 tumoral lesions), hazard ratio (HR) for progression of 0.51 (P =
      0.002) and for death of 0.59 (P = 0.017); and initiation of mitotane at delayed
      advanced recurrence, HR 0.35(P < 0.001) and 0.34 (P < 0.001), respectively.
      Accordingly, 67% of patients with low tumor burden and mitotane initiation >=360
      days after primary diagnosis experienced a clinical benefit (stable disease >180
      days). Patients who achieved mitotane levels >14 mg/L had significantly longer OS
      (HR 0.42; P = 0.003). Conclusions: At 20.5% the objective response rate was
      slightly lower than previously reported. However, >20% of patients experienced
      long-term disease control at >1 year. In general, patients with late diagnosis of
      advanced disease and low tumor burden might especially benefit from mitotane
      monotherapy, whereas patients with early advanced disease and high tumor burden
      are probably better candidates for combined therapy of mitotane and cytotoxic
      drugs.

PMID- 29452404
TI  - Vitamin E and vitamin C supplementation improves antioxidant status and immune
      function in oxidative-stressed breeder roosters by up-regulating expression of
      GSH-Px gene.
AB  - This study aimed to evaluate the effects of vitamin C and vitamin E on
      antioxidant capacity and immune function in oxidative-stressed breeder roosters.
      One hundred twenty 45-week-old Lveyang black-boned breeder roosters were randomly
      assigned to 5 dietary treatments, including negative control group (NC), positive
      control group (PC), and 3 trial groups, which were fed the diets containing 300
      mg/kg VC, 200 mg/kg VE, or 300 mg/kg VC and 200 mg/kg VE (VC+VE). At 47 wk of
      age, the positive control and trial groups were subcutaneously injected 3 times
      every other d with dexamethasone (DEX) 4 mg/kg of body weight, the negative
      control group was injected with saline. The experiment lasted for 35 d. The
      results showed that at 50 wk of age, average daily feed intake of birds
      challenged with DEX significantly increased (P < 0.05). During post-stress
      recovery period (52 wk of age), dietary supplemental VE or VC+VE notably
      increased body weight under oxidative stress (P < 0.01). Oxidative stress induced
      by DEX could significantly decrease superoxide dismutase (SOD), IgM, antibody
      titer of ND and mRNA expression of SOD or glutathion peroxidase activity (GSH
      Px), increase serous malondialdehyde (MDA) (P < 0.05). Supplementation of VC or
      VE significantly decreased serous MDA, and increased SOD under oxidative stress
      (P < 0.05). Supplementation of VC or VE, or their combination significantly
      increased the relative expression of GSH-Px mRNA when compared to the oxidative
      stressed control treatment (P < 0.05), whereas did not alleviate the relative
      expression of SOD mRNA (P > 0.05). Therefore, the results suggest that addition
      of 300 mg/kg VC, 200 mg/kg VE or their combination could improve antioxidant
      ability and immune performance in oxidative-stressed breeder roosters through up
      regulating the expression of GSH-Px gene.

PMID- 29452405
TI  - Commentary: Neurosurgery and the Ongoing American Opioid Crisis.

PMID- 29452406
TI  - Negative Association Between Sclerostin and INSL3 in Isolated Human Osteocytes
      and in Klinefelter Syndrome: New Hints for Testis-Bone Crosstalk.
AB  - Context: The regulation of bone mass by the testis is a well-recognized
      mechanism, but the role of Leydig-specific marker insulin-like 3 peptide (INSL3)
      on the most abundant bone cell population, osteocytes, is unknown. In this study,
      we aimed to investigate the relationship between INSL3 and sclerostin, an
      osteocyte-specific protein that negatively regulates bone formation. Design:
      Serum sclerostin and INSL3 levels were evaluated in Klinefelter syndrome (KS) and
      healthy controls. In vitro effect of INSL3 on sclerostin production was evaluated
      in human cultured osteocytes. Patients: A total of 103 KS patients and 60 age-
      and sex-matched controls were recruited. Main Outcome Measures: Serum sclerostin
      and INSL3 levels were assessed by enzyme-linked immunosorbent assay. Osteocytes
      were isolated by fluorescence-assisted cell sorting. Sclerostin expression was
      evaluated by western blot, immunofluorescence, and reverse transcription
      polymerase chain reaction. Measurement of bone mineral density was done by dual
      energy X-ray absorptiometry at lumbar spine (L1-L4) and femoral neck. Results:
      Sclerostin levels were significantly increased in KS subjects, and negatively
      correlated with INSL3 levels in both cohorts and with bone mineral density in the
      KS group. Stimulation of cultured osteocytes with INSL3 at 10-7 M significantly
      decreased both sclerostin messenger RNA and protein expression. Conclusions: We
      report a negative association between the testicular hormone INSL3 and the
      osteocytic negative regulator of bone formation, sclerostin. We further explored
      this association in vitro and showed that INSL3 was able to reduce sclerostin
      expression. These results add further knowledge on the emerging role of
      sclerostin as a therapeutic target for osteoporosis treatment.

PMID- 29452407
TI  - Dietary L-glutamine supplementation improves growth performance, gut morphology,
      and serum biochemical indices of broiler chickens during necrotic enteritis
      challenge.
AB  - Necrotic enteritis (NE) causes significant economic losses in the broiler chicken
      industry, especially in birds raised without in-feed antibiotics. L-glutamine
      (Gln) is an amino acid that may compensate for metabolic losses from infection
      and improve the intestinal development. This study investigated the effects of
      dietary Gln (10 g/kg) supplementation on growth performance, intestinal lesions,
      jejunum morphology, and serum biochemical indices of broiler chickens during NE
      challenge. The study employed a factorial arrangement of treatments with factors:
      NE challenge, no or yes; dietary Gln inclusion, 0 g/kg in starter (S), d 0 to 10,
      grower (G) d 10 to 24, and finisher (F) d 24 to 35; 10 g/kg in S, G, F, or 10
      g/kg in S, G only. Each treatment was replicated in 6 floor pens with 17 birds
      per pen as the experimental unit for performance and 2 birds for other
      measurements. Challenge significantly reduced bird performance, increased
      incidence of intestinal lesions, and affected intestinal development and serum
      biochemical indices. Regardless of challenge, Gln supplementation increased gain
      (P < 0.05), feed intake (P < 0.05), and decreased FCR (P < 0.05) on d 24. On d
      35, Gln improved gain (P < 0.05) and FCR (P < 0.001) whereas withdrawing Gln from
      finisher tended to diminish the beneficial effect on weight gain but not FCR.
      Dietary Gln reduced lesion scores in the jejunum (P < 0.01) and ileum (P < 0.01)
      in challenged birds. On d 16, Gln increased villus height to crypt depth ratio in
      unchallenged birds (P < 0.05) and reduced crypt depth of challenged birds on d 24
      (P < 0.05). Regardless of challenge, supplementation with Gln reduced crypt depth
      on d 16 (P < 0.05), and increased villus height (P < 0.01) and the villus height
      to crypt depth ratio (P < 0.001) on d 24. Dietary Gln lowered serum uric acid
      level regardless of challenge (P < 0.05). The current study indicates that
      dietary Gln alleviates adverse effects of NE and may be useful in antibiotic-free
      diets.

PMID- 29452410
TI  - Irene Lang MD.

PMID- 29452411
TI  - Engaging patients in their medical care.

PMID- 29452409
TI  - Recruitment and retention of trainee physicians: a retrospective analysis of the
      motivations and influences on career choice of trainee physicians.
AB  - Background: Across the UK, there are vacant physician posts at every level. This
      increases workload and stress for those who remain, in turn making substantive
      jobs less attractive. Aim: To understand the influences on career choice and
      retention in training of current trainee physicians. Methods: An online survey,
      with a combination of closed and free text questions, was developed to assess
      factors that affected career choices. This was sent to all core and higher
      specialty trainees in Scotland and Associate or Collegiate members of the Royal
      College of Physicians Edinburgh not training in Scotland. Results: A total of 846
      trainees responded, 231 of whom were trainee physicians; 161 (70%) of trainee
      physicians stated that experience prior to their current role had a very positive
      impact on career choice, particularly positive role modelling and informal career
      advice. Core trainees were less likely to report enjoying their job than higher
      specialty trainees with 31 (50%) found to enjoy their job 'always' or 'most of
      the time' in comparison to 114 (79%). About 181 (78%) of trainees selected
      through national recruitment of which 77 (42%) were moderately satisfied and 32
      (8%) completely satisfied with the process. Uncertainty of job location and
      inability to demonstrate professional ability were the main complaints.
      Conclusions: Career choices are influenced by role models and informal careers
      advice. Efforts must be made to improve the experience trainees, particularly
      those in core training. Current physicians, both trainees and consultants, have
      an important role in recruiting the next generation of trainee physicians-this
      must be supported.

PMID- 29452412
TI  - The GPCC.

PMID- 29452408
TI  - Genome-wide association study identifies seven novel susceptibility loci for
      primary open-angle glaucoma.
AB  - Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness
      worldwide for which 15 disease-associated loci had been discovered. Among them,
      only 5 loci have been associated with POAG in Asians. We carried out a genome
      wide association study and a replication study that included a total of 7378 POAG
      cases and 36 385 controls from a Japanese population. After combining the genome
      wide association study and the two replication sets, we identified 11 POAG
      associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7
      novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a
      genome-wide significance level (P < 5.0*10-8), bringing the total number of POAG
      susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a
      multiethnic population comprising non-Japanese East Asians (1008 cases, 591
      controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037
      controls). The candidate genes located within the new loci were related to ocular
      development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B,
      LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor
      signaling might be involved in POAG pathogenesis. Genetic correlation analysis
      revealed the relationships between POAG and systemic diseases, including type 2
      diabetes and cardiovascular diseases. These results improve our understanding of
      the genetic factors that affect the risk of developing POAG and provide new
      insight into the genetic architecture of POAG in Asians.

PMID- 29452414
TI  - Peace Plaque for the city of Barcelona.

PMID- 29452413
TI  - Ferrara IV.

PMID- 29452415
TI  - Epidemiology of cardiovascular disease: the new ESC Atlas and beyond.

PMID- 29452416
TI  - Early and Midlife Predictors of Wisdom and Subjective Well-Being in Old Age.
AB  - Objectives: We explored whether wisdom and well-being in old age are the result
      of early personality traits related to personality growth or personality
      adjustment, respectively, or successful human development as outlined by
      Erikson's stage theory and the life course paradigm. Method: Structural equation
      models were applied to analyze 60-year longitudinal data of 98 white male Harvard
      graduates born between 1915 and 1924. Different sets of judges rated the men's
      childhood and adolescence, early adult personality, and midlife generativity.
      Items measuring wisdom and well-being in old age were self-assessed. Results:
      Although wisdom and subjective well-being at age 80 were positively correlated,
      early life predictors differed. Openness to experiences in early adulthood
      predicted wisdom 60 years later, whereas greater emotional stability and
      extraversion predicted subjective well-being. Additionally, old age wisdom could
      be traced back to psychosocial growth throughout life, facilitated by a
      supportive childhood, adolescent competence, emotional stability in early
      adulthood, and generativity at midlife. Discussion: Personality traits indicative
      of personality adjustment or growth differentially predict late-life well-being
      and wisdom. Yet a balance between personality adjustment and growth, aided by
      social support and competence during the formative years, might be required to
      promote wisdom development throughout life.

PMID- 29452417
TI  - Fruit production and branching density affect shoot and whole-tree wood to leaf
      biomass ratio in olive.
AB  - The amount of shoot stem (i.e., woody part of the shoot) dry matter per unit
      shoot leaf dry matter (i.e., the shoot wood to leaf biomass ratio) has been
      reported to be lower in short shoots than in long ones, and this is related to
      the greater and earlier ability of short shoots to export carbon. This is
      important in fruit trees, since the greater and earlier carbon export ability of
      shoots with a lower wood to leaf biomass ratio improves fruit production. This
      ratio may vary with cultivars, training systems or plant age, but no study has
      previously investigated the possible effect of fruit production. In this study on
      two olive cultivars (i.e., Arbequina, with low growth rate, and Frantoio, with
      high growth rate) subject to different fruit production treatments, we found that
      at increasing fruit production, shoot length and shoot wood to leaf biomass ratio
      were proportionally reduced in the new shoots growing at the same time as the
      fruit. Specifically, fruit production proportionally reduced total new-shoot
      biomass, length, leaf area and average shoot length. With decreasing shoot
      length, shoot diameter, stem mass, internode length, individual leaf area and
      shoot wood to leaf biomass ratio also decreased. This may be viewed as a plant
      strategy to better support fruit growth in the current year, given the greater
      and earlier ability of short shoots to export carbon. Moreover, at the whole-tree
      level, the percentage of total tree biomass production invested in leaves was
      closely correlated with branching density, which differed significantly across
      cultivars. By branching more, Arbequina concentrates more shoots (thus leaves)
      per unit of wood (trunk, branches and root) mass, decreasing wood to leaf biomass
      ratio at the whole-tree level. Therefore, while, at the shoot level, shoot length
      determines shoot wood to leaf biomass ratio, at the canopy level branching
      density is also an important determinant of whole-tree wood to leaf biomass
      ratio. Whole-tree wood to leaf biomass ratio is likely to affect the canopy's
      ability to export carbon (i.e., towards fruits), as shoot wood to leaf biomass
      ratio affects the carbon export ability of the shoot.

PMID- 29452418
TI  - PHF20 collaborates with PARP1 to promote stemness and aggressiveness of
      neuroblastoma cells through activation of SOX2 and OCT4.
AB  - The differentiation status of neuroblastoma (NB) strongly correlates with its
      clinical outcomes; however, the molecular mechanisms driving maintenance of
      stemness and differentiation remain poorly understood. Here, we show that plant
      homeodomain finger-containing protein 20 (PHF20) functions as a critical
      epigenetic regulator in sustaining stem cell-like phenotype of NB by using
      CRISPR/Cas9-based targeted knockout (KO) for high-throughput screening of gene
      function in NB cell differentiation. The expression of PHF20 in NB was
      significantly associated with high aggressiveness of the tumor and poor outcomes
      for NB patients. Deletion of PHF20 inhibited NB cell proliferation, invasive
      migration, and stem cell-like traits. Mechanistically, PHF20 interacts with
      poly(ADP-ribose) polymerase 1 (PARP1) and directly binds to promoter regions of
      octamer-binding transcription factor 4 (OCT4) and sex determining region Y-box 2
      (SOX2) to modulate a histone mark associated with active transcription,
      trimethylation of lysine 4 on histone H3 protein subunit (H3K4me3).
      Overexpression of OCT4 and SOX2 restored growth and progression of PHF20 KO tumor
      cells. Consistently, OCT4 and SOX2 protein levels in clinical NB specimens were
      positively correlated with PHF20 expression. Our results establish PHF20 as a key
      driver of NB stem cell-like properties and aggressive behaviors, with
      implications for prognosis and therapy.

PMID- 29452420
TI  - Gut Microbiomics-A Solution to Unloose the Gordian Knot of Biological Effects of
      Ionizing Radiation.
AB  - The Chernobyl and Fukushima nuclear accidents have called forth a growing body of
      research on their biological aftermaths. A variety of wild organisms, including
      primates, birds, fish, insects, and worms are being studied in the affected
      areas, with emerging morphological, physiological, and genetic aberrations
      ascribed to ionizing radiation. Despite the effort in surveying Chernobyl and
      Fukushima wildlife, little is known about the microorganisms associated with
      these radiation-contaminated animals. The microbiota, especially the gut
      commensal, plays an important role in shaping the metabolic reservoir and immune
      system of the host, and is sensitive to a wide array of environmental factors,
      including ionizing radiation. Humans and limited numbers of laboratory species
      have been the main subjects of microbiome studies, however, a more practical
      insight on host-gut microbiota dynamics under environmental impact should be
      explored in natural habitats. In this analysis, we introduced a working model
      explaining possible mechanisms of ionizing radiation on the gut microbiota, with
      an evaluation of the gut microbiota as a potential biomarker for exposure to
      ionizing radiation.

PMID- 29452419
TI  - Temozolomide-associated hypermutation in gliomas.
AB  - Low-grade gliomas cause considerable morbidity and most will recur after initial
      therapy. At recurrence, low-grade gliomas can undergo transformation to high
      grade gliomas (grade III or grade IV), which are associated with worse prognosis.
      Temozolomide (TMZ) provides survival benefit in patients with glioblastomas, but
      its value in patients with low-grade gliomas is less clear. A subset of TMZ
      treated, isocitrate dehydrogenase-mutant, low-grade astrocytomas recur as more
      malignant tumors with thousands of de novo, coding mutations bearing a signature
      of TMZ-induced hypermutation. Preliminary studies raise the hypothesis that TMZ
      induced hypermutation may contribute to malignant transformation, although with
      highly variable latency. On the other hand, hypermutated gliomas have radically
      altered genomes that present new opportunities for therapeutic intervention. In
      light of these findings and the immunotherapy clinical trials they inspired, how
      do patients and providers approach the risks and benefits of TMZ therapy? This
      review discusses what is known about the mechanisms and consequences of TMZ
      induced hypermutation and outstanding questions regarding its clinical
      significance.

PMID- 29452421
TI  - The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS.
AB  - Background: The cosyntropin test is used to diagnose adrenal insufficiency (AI)
      and nonclassical congenital adrenal hyperplasia (NCCAH). Current cutoffs for
      cortisol and 17-hydroxyprogesterone (17-OHP) are derived from nonstandardized
      immunoassays. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers
      direct measurement of steroids, prompting the need to re-establish normal ranges.
      Objective: The goal of this study was to define cutoff values for cortisol and 17
      OHP in serum by LC-MS/MS 30 and 60 minutes after intravenous administration of
      250 ug tetracosactide acetate to healthy volunteers and to compare the results
      with LC-MS/MS with routine immunoassays. Methods: Cosyntropin testing was
      performed in healthy subjects (n = 138) and in patients referred for evaluation
      of adrenocortical function (n = 94). Steroids were assayed by LC-MS/MS and
      compared with two immunoassays used in routine diagnostics (Immulite and Roche
      platforms). The cutoff level for cortisol was defined as the 2.5% percentile in
      healthy subjects not using oral estrogens (n = 121) and for 17-OHP as the 97.5%
      percentile. Results: Cortisol cutoff levels for LC-MS/MS were 412 and 485 nmol/L
      at 30 and 60 minutes, respectively. Applying the new cutoffs, 13 of 60 (22%)
      subjects who had AI according to conventional criteria now had a normal test
      result. For 17-OHP, the cutoff levels were 8.9 and 9.0 nmol/L at 30 and 60
      minutes, respectively. Conclusions: LC-MS/MS provides cutoff levels for cortisol
      and 17-OHP after cosyntropin stimulation that are lower than those based on
      immunoassays, possibly because cross-reactivity between steroid intermediates and
      cortisol is eliminated. This reduces the number of false-positive tests for AI
      and false-negative tests for NCCAH.

PMID- 29452422
TI  - Asynchronous and pathological windows of implantation: two causes of recurrent
      implantation failure.
AB  - STUDY QUESTION: Is endometrial recurrent implantation failure (RIF) only a matter
      of an asynchronous (displaced) window of implantation (WOI), or could it also be
      a pathological (disrupted) WOI? SUMMARY ANSWER: Our predictive results
      demonstrate that both displaced and disrupted WOIs exist and can present
      independently or together in the same RIF patient. WHAT IS KNOWN ALREADY: Since
      2002, many gene expression signatures associated with endometrial receptivity and
      RIF have been described. Endometrial transcriptomics prediction has been applied
      to the human WOI in two previous studies. One study describes endometrial RIF to
      be the result of a temporal displacement of the WOI. The other indicates that
      endometrial RIF can also result from a molecularly disrupted WOI without temporal
      displacement. STUDY DESIGN, SIZE, DURATION: Retrospective analysis was undertaken
      to compare WOI endometrial transcriptomics predictions in controls (n = 72) and
      RIF patients (n = 43). RIF was clinically designated by the absence of
      implantation after four or more transfers of high quality embryos or after the
      placement of 10 or more embryos in multiple transfers. Endometrial tissue samples
      were collected from LH + 5 to LH + 8. We compared the two molecular causes of RIF
      to signatures currently described in the literature. We propose a new
      transcriptomic RIF taxonomy to fill the gap between the two hypotheses and to
      guide the development of clinical detection and determination of both types of
      RIF. PARTICIPANTS/MATERIALS, SETTING, METHODS: Utilizing 115 gene expression
      profiles, two different predictive designs were developed: one considering RIF
      versus controls removing menstrual cycle timing, called the disrupted or
      pathological model, and another stratifying the WOI in transcriptomic profiles
      related to timing for predicting displacements. The predictive value of each
      model was compared between all signatures selected. We propose a new genomic
      approach that distinguishes between both types of RIF in the same sample cohort.
      MAIN RESULTS AND THE ROLE OF CHANCE: From the 16 signatures analysed, we clearly
      predicted two causes of RIF-both a displaced WOI and an on-time but
      pathologically disrupted WOI. A high predictive value related to WOI profiles
      associated with menstrual cycle timing was found in most of the signatures.
      Specifically, 69% of the signatures analysed presented an accuracy higher than
      expected by chance in a range from 0.87 to 0.97. Displacements and disruptions
      were not molecularly independent, as some signatures were moderately associated
      with both causes. The gene and functional comparison between signatures revealed
      that they were not similar, although we did find functions in common and a
      cluster of moderate functional concordance between some of the signatures that
      predicted displacements (the highest Cohen's Kappa index were between 0.55 and
      0.62 depending on the functional database). We propose a new transcriptomic RIF
      taxonomy to fill the gap between these prior studies and to establish methodology
      for detecting and distinguishing both types of RIF in clinical practice. Our
      findings indicate these two phenotypes could present independently or together in
      the same RIF patient. RIF patients designated by clinical criteria have been
      stratified transcriptomically as 18.6% with only a displaced WOI, 53.5% with a
      displaced and pathological WOI, 23.3% with only a disrupted WOI, and 4.7% could
      be a clinical RIF with non-endometrial origin. The new RIF transcriptomic
      taxonomy avoids menstrual cycle timing as a confounding variable that should be
      controlled for, distinguishing clearly between a disrupted and a displaced WOI
      for precision medicine in RIF. LIMITATIONS REASONS FOR CAUTION: The main
      objective of this study was to use transcriptomics to detect both RIF causes and
      to understand the role of transcriptomic signatures in these phenotypes. The
      predictive value in absolute terms for each signature was not indicative in these
      prediction designs; instead, the comparison between signatures was most important
      for prediction capability in the same sample cohort for both RIF causes. Clinical
      follow up of the RIF taxonomies proposed has not been analysed in this study, so
      further prospective clinical studies are necessary to determine the prevalence
      and penetrance of these phenotypes. WIDER IMPLICATIONS OF THE FINDINGS: The main
      insight from this study is a new understanding of RIF taxonomy. Understanding how
      to classify RIF patients to distinguish clinically between a patient who could
      benefit from a personalized embryo transfer day and a patient with a disrupted
      WOI will enable identification and stratification for the research and
      development of new treatments. In addition, we demonstrate that basic research
      designs in endometrial transcriptomics cause masking of the study variable by the
      menstrual cycle timing. STUDY FUNDING/COMPETING INTEREST(S): This research has
      been funded by IVI-RMA; the authors do not have any competing interests.

PMID- 29452423
TI  - Anti-citrullinated alpha enolase antibodies, interstitial lung disease and bone
      erosion in rheumatoid arthritis.
AB  - Objectives: RA is an articular chronic inflammatory disease that in a subgroup of
      patients can also present with extra-articular manifestations (EAMs). Despite
      intense investigation on this topic, reliable biomarkers for EAMs are lacking. In
      recent years several ACPAs, including those targeting anti-citrullinated alpha
      enolase peptide-1 (anti-CEP-1), have been identified in patients with RA. Data
      about the ability of anti-CEP-1 to predict the development of erosive disease are
      confliciting and no evidence concerning their possible association with EAMs in
      RA is currently available. The aim of this study was to investigate the
      prevalence and significance of anti-CEP-1 with regard to the association with
      erosive disease and EAMs in a large cohort of patients with RA. Methods: Anti-CCP
      and anti-CEP-1 antibodies have been assessed on serum samples of RA patients,
      healthy donors and patients with SpA using commercially available ELISA kits.
      Results: Anti-CEP-1 antibodies are detectable in over 40% of RA patients and are
      associated with erosive RA and with RA-associated interstitial lung disease
      (ILD). Conclusion: Anti-CEP-1 antibodies may represent a useful biomarker for RA
      associated ILD and erosive disease to be employed in clinical practice.

PMID- 29452424
TI  - Age-related changes in survival and turnover rates of balsam fir (Abies balsamea
      (L.) Mill.) fine roots.
AB  - Fine-root (<=2 mm) demographics change as forests age, but the direction and
      extent of change are unknown. Knowledge of the change and understanding of causes
      will improve predictions of climate change impacts. We used minirhizotrons at
      three young and three mature balsam fir (Abies balsamea (L.) Mill.) sites to
      measure median lifespan (MLS) for each site and for annual cohorts. We computed
      turnover rate from the inverse of MLS (Tinv) and calculated a second turnover
      rate (T) from annual mortality, annual production and previous year-end standing
      crop. Median lifespan at mature sites (436 days) was half that at young sites
      (872 days). Median lifespan of annual cohorts varied widely at all sites. Age
      class distributions of fine roots seen by minirhizotrons changed with increasing
      years of observation, with older age classes accumulating more slowly at mature
      sites. Our findings highlight the need to determine whether the proportional
      contributions of absorbing and transporting fine roots to annual production and
      their median lifespans change during stand development. Due to its variation
      among annual cohorts, we believe robust estimates of MLS at our sites require 5-7
      years of observation, and reliable estimates of Tinv are reached earlier than T.

PMID- 29452425
TI  - Clinical evidence on dietary supplementation with chia seed (Salvia hispanica
      L.): a systematic review and meta-analysis.
AB  - Context: Chia seed is a popular dietary supplement, taken mainly for its high
      content of alpha-linolenic acid, vegetable protein, and dietary fiber, yet
      information about its clinical effects is lacking. Objective: This review aims to
      summarize the clinical evidence regarding the use of chia seed for a wide variety
      of health conditions. Data Sources: A number of databases, including PubMed and
      Embase, were searched systematically. Study Selection: Randomized controlled
      trials that assessed the clinical effects of chia seed consumption in human
      participants were included. The quality of trials was assessed using the Cochrane
      Risk of Bias Tool. Data Extraction: Data on study design, blinding status,
      characteristics of participants, chia seed intervention, comparator, clinical
      assessment, duration of intake, interval of assessment, and study funding status
      were extracted. Meta-analysis was performed. Results: Twelve trials were
      included. Participants included healthy persons, athletes, diabetic patients, and
      individuals with metabolic syndrome. Pooling of results showed no significant
      differences except for the following findings of subgroup analysis at higher
      doses of chia seed: (1) lower postprandial blood glucose level (mean difference
      [MD] of -33.95 incremental area under the curve [iAUC] [mmol/L * 2 h] [95%CI, 
      61.85, -6.05] and -51.60 iAUC [mmol/L * 2 h] [95%CI, -79.64, -23.56] at medium
      doses and high doses, respectively); (2) lower high-density lipoprotein in serum
      (MD of -0.10 mmol/L [95%CI, -0.20, -0.01]); and (3) lower diastolic blood
      pressure (MD of -7.14 mmHg [95%CI, -11.08, -3.19]). The quality of all evidence
      assessed using the Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) approach was low or very low. All trials employed only
      surrogate markers as outcomes. Conclusions: Future trials with improved
      methodological quality, well-described clinical events, and validated surrogate
      markers as outcomes are needed to support the potential health benefits of chia
      seed consumption. Systematic Review Registration: PROSPERO registration no.
      CRD42015029990.

PMID- 29452426
TI  - Open Access, data capitalism and academic publishing.
AB  - Open Access (OA) is widely considered a breakthrough in the history of academic
      publishing, rendering the knowledge produced by the worldwide scientific
      community accessible to all. In numerous countries, national governments, funding
      institutions and research organisations have undertaken enormous efforts to
      establish OA as the new publishing standard. The benefits and new perspectives,
      however, cause various challenges. This essay addresses several issues, including
      that OA is deeply embedded in the logic and practices of data capitalism. Given
      that OA has proven an attractive business model for commercial publishers, the
      key predictions of OA-advocates, namely that OA would liberate both scientists
      and tax payers from the chains of global publishing companies, have not become
      true. In its conclusion, the paper discusses the opportunities and pitfalls of
      non-commercial publishing.

PMID- 29452427
TI  - Effect of Routine, Screening Head Ultrasounds on Clinical Interventions for
      Premature Infants.
AB  - OBJECTIVE:  This article assesses whether routine, screening head ultrasound
      (HUS) studies performed at 7 to 14 postnatal days for premature infants are
      followed by clinical interventions. STUDY DESIGN:  This retrospective cohort
      study included all inborn infants delivered at < 30 weeks' gestational age (GA)
      between January 1, 2012 and December 31, 2015 at a single center who had a
      routine, screening HUS performed between 7 and 14 postnatal days (n = 303). We
      defined "clinical intervention" as a 7 to 14 postnatal day HUS that was followed
      by neurosurgical intervention prior to a 36- to 40-week postmenstrual age (PMA)
      HUS or elective withdrawal of critical care within 30 days of a positive HUS
      finding. RESULTS:  Four infants (1.3%) had neurosurgical intervention prior to a
      36- to 40-week PMA HUS; all four had a diagnostic HUS performed prior to
      postnatal day 7 to assess for an intraventricular hemorrhage (IVH) due to
      clinical instability. No infant had critical care electively withdrawn following
      a 7 to 14 postnatal day HUS. CONCLUSION:  Clinical intervention rarely followed
      routine, screening HUS studies performed at 7 to 14 postnatal days for inborn
      infants delivered at < 30 weeks' GA. In no case did clinical intervention related
      to HUS results occur when a 7 to 14 postnatal day HUS was the initial HUS
      performed.

PMID- 29452428
TI  - Illness Severity Predicts Death and Brain Injury in Asphyxiated Newborns Treated
      with Hypothermia.
AB  - OBJECTIVE:  To determine if illness severity during the first days of life
      predicts adverse outcome in asphyxiated newborns treated with hypothermia. STUDY
      DESIGN:  We conducted a retrospective cohort study of asphyxiated newborns
      treated with hypothermia. Illness severity was calculated daily during the first
      4 days of life using the Score for Neonatal Acute Physiology II (SNAP-II score).
      Adverse outcome (death and/or brain injury) was recorded. Differences in SNAP-II
      scores between the newborns with and without adverse outcome were assessed.
      RESULT:  214 newborns were treated with hypothermia. The average SNAP-II score
      over the first 4 days of life was significantly worse in newborns developing
      adverse outcome. The average SNAP-II score was an excellent predictor of death
      (area under the curve [AUC]: 0.93; p < 0.001) and a fair predictor of adverse
      outcome (AUC: 0.73; p < 0.001). The average SNAP-II score remained a significant
      predictor of adverse outcome (odds ratio [95% confidence interval]: 1.08 [1.04
      1.12]; p < 0.001), after adjusting for baseline characteristics, degree of
      initial asphyxial event, and initial severity of encephalopathy. CONCLUSION:  In
      asphyxiated newborns treated with hypothermia, not only the initial asphyxial
      event but also the illness severity during the first days of life was a
      significant predictor of death or brain injury.

PMID- 29452429
TI  - Less invasive than minimally invasive: peroral endoscopic myotomy with a slim
      scope in the treatment of esophageal achalasia.

PMID- 29452430
TI  - Combined endoscopic submucosal dissection and transanal minimally invasive
      surgery for resection of large refractory rectal polyp.

PMID- 29452431
TI  - Endosonography-guided hepatogastrostomy post-percutaneous biliary drainage in
      collaboration with interventional radiology.

PMID- 29452432
TI  - Acute pancreatitis: ascaris in the pancreatic duct.

PMID- 29452433
TI  - Successful digital cholangioscopy removal of a stent-retriever tip migrated into
      the periphery of the bile duct.

PMID- 29452434
TI  - Long-term result of endoscopic treatment of an ampullary adenoma with extension
      into the common bile duct.

PMID- 29452435
TI  - Dynamic lumen obstructing angulation in advanced sigmoid-type achalasia
      successfully treated by additional proximal curve myotomy.

PMID- 29452436
TI  - Cholangioscopy-guided electrohydraulic lithotripsy of large bile duct stones
      through a percutaneous access device.

PMID- 29452437
TI  - Successful treatment of giant esophageal diverticulum by per-oral endoscopic
      myotomy.

PMID- 29452438
TI  - Algorithmic Approach for Intraoperative Salvage of Venous Congestion in DIEP
      Flaps.
AB  - BACKGROUND:  Flap congestion is a frequently described intraoperative
      complication during autologous breast reconstruction with abdominal perforator
      flaps, which, if not addressed, can lead to detrimental results such as flap
      failure. Here, we describe our institution's algorithm of intraoperative salvage
      of congested flaps and present their outcomes. PATIENTS AND METHODS:  All patient
      charts from 2002 to 2016 of a single plastic surgeon were reviewed for patients
      who underwent deep inferior epigastric perforator flap breast reconstruction
      resulting in 602 patients and 831 flaps. Of those, 38 women (6.3%) with 40
      congested flaps (4.8%) were included in this study. Based on the algorithm
      guiding the selection of additional venous anastomosis, the patients' surgical
      details, outcomes, as well as their demographic characteristics are evaluated.
      RESULTS:  Average age and body mass index of our cohort were 47.0 +/- 8.0 years
      and 26.1 +/- 3.9, respectively. Ten patients (26.3%) were current or former
      smokers while 20 (52.6%) required external radiation. Thirty-two congested flaps
      (80.0%) were predominantly salvaged with a superficial inferior epigastric vein
      (SIEV)-to-deep inferior epigastric vein (comitante) anastomosis. An SIEV-to
      internal mammary vein comitante anastomosis was the second favorite option (5
      flaps, 12.5%). Five patients suffered minor complications within a mean follow-up
      of 18.8 +/- 12.3 months without flap failure, bleeding, or infection.
      CONCLUSIONS:  Venous flap congestion is an uncommon intraoperative intricacy
      during free tissue transfer for autologous breast reconstruction. Our proposed
      algorithm primarily recommends adding an additional venous anastomosis between
      the superficial and deep drainage system and results and favorable outcomes
      without major complications.

PMID- 29452439
TI  - Assessment of Function after Free Tissue Transfer to the Lower Extremity for
      Chronic Wounds Using the Lower Extremity Functional Scale.
AB  - BACKGROUND:  Free tissue transfer is one option for preservation of form and
      function in the native limb, in the setting of soft tissue paucity. However, the
      data on patient functionality after microvascular intervention is inconsistently
      reported. The Lower Extremity Function Scale (LEFS) measures patient-reported
      difficulty in carrying out 20 physical activities, on a Likert scale, the sum of
      which correlates with descriptive functional stages of 1-5. We assess limb
      functionality in this cohort of microvascular patients using the LEFS survey.
      METHODS:  A retrospective chart review was conducted at a single academic medical
      center of 101 consecutive free flaps, from 2011 to 2016. Of the flaps that met
      inclusion criteria, 39 had completed LEFS surveys. Mean LEFS scores were
      calculated, and the effects of risk factors such as diabetes, age, and smoking
      status were analyzed. RESULTS:  The mean LEFS score after free tissue transfer
      was 50.3 (SD +/- 21.1), with a mean follow up survey time of 3.0 years (SD +/-
      1.3). The score correlated with Stage 4 function, or "independent community
      ambulation," and age was the only demographic factor associated with decreased
      functionality in this group. This is compared with mean LEFS score of 43.1 (SD +/
      18.4) in cohort of 55 below knee amputations (BKAs), and 38.3 (SD +/- 14.9) in
      28 above knee amputations (AKAs), both correlating with Stage 3 function:
      "limited community ambulation." CONCLUSIONS:  Functional outcomes scores such as
      the LEFS demonstrate that patients can obtain an adequate level of functionality
      for independent community activity after free tissue transfer, although
      functional improvement diminishes with age.

PMID- 29452440
TI  - Operative Time and Flap Failure in Unilateral and Bilateral Free Flap Breast
      Reconstruction.
AB  - BACKGROUND:  There is an increasing trend toward bilateral breast reconstruction.
      Using the National Surgical Quality Improvement Program (NSQIP) database, we
      sought to understand the association between unilateral and bilateral free flap
      breast reconstruction and operative time and flap failure. METHODS:  We selected
      a cohort of patients undergoing free flap breast reconstruction using the 2005 to
      2010 NSQIP database. Cases were divided into unilateral and bilateral
      reconstruction. Subgroup analyses were performed dividing cases into delayed and
      immediate reconstruction. The effect of patient characteristics including age,
      body mass index (BMI), history of diabetes, and the American Society of
      Anesthesiologists' classification on operative time and flap failure was examined
      using univariable and multivariable regression models. Rates and odds ratios (OR)
      were reported using the multivariable gamma and logistic regression models,
      respectively. RESULTS:  There were 691 free flap breast reconstructions performed
      in the cohort and 29.1% were bilateral cases. There was a 78-minute increase in
      the median operative time when comparing unilateral and bilateral reconstruction
      (p = 0.005). Patients undergoing bilateral reconstructions were generally younger
      and had fewer comorbidities compared with unilateral reconstructions. There was
      no significant association between bilateral reconstruction and flap failure.
      Immediate bilateral reconstructions had a significant increase in median
      operative time compared with immediate unilateral reconstructions (563 versus 480
      minutes, p = 0.002) but no significant increase in operative time was noted when
      comparing delayed unilateral and delayed bilateral reconstructions. Prolonged
      operative time was associated with flap failure after adjusting for age and BMI
      (OR 1.17, p < 0.001). CONCLUSIONS:  Bilateral free flap breast reconstruction can
      be performed safely despite an increase in operative time when compared with
      unilateral reconstruction.

PMID- 29452441
TI  - Assessing the Safety and Efficacy of Regional Anesthesia for Lower Extremity
      Microvascular Reconstruction: Enhancing Recovery.
AB  - BACKGROUND:  Perioperative pain, increased sympathetic tone, and peripheral
      vasospasm may be safely managed with regional nerve blockade during microvascular
      reconstruction in the lower extremity. Limited reports exist in this setting;
      therefore, we evaluated our use of peripheral nerve catheters (PNCs) during
      microvascular limb salvage to determine safety and efficacy for both patient and
      flap. METHODS:  A single-institution, retrospective review of a prospectively
      maintained database on all patients with lower extremity free tissue transfers
      between 2012 and 2017 was completed. Patients were matched into groups based on
      PNC utilization. The use of intravenous narcotics including patient-controlled
      analgesia (PCA), oral narcotics, antiemetics, length of stay (LOS), associated
      pain scores, flap-related performance, and patient morbidity was recorded.
      RESULTS:  Of 48 patients who underwent lower extremity free tissue transfer, 35
      satisfied criteria for comparison. Of these, PNC was utilized in 83%. The mean
      pain score in the immediate postoperative period was 3.84 +/- 2.47 (10-point
      Likert scale). PCA and narcotic use were decreased in the PNC group, and no
      adverse effects of the catheter were identified. Microsurgical outcomes were not
      adversely affected in comparison. CONCLUSION:  PNC utilization for lower
      extremity free flap transfer significantly reduced concurrent narcotic use and
      attained a shorter LOS. The technique provided for safe analgesia during lower
      extremity free flap reconstructions satisfying the microsurgeon and the
      anesthesiologist.

PMID- 29452442
TI  - Simplifying Arterial Coupling in Microsurgery-A Preclinical Assessment of an
      Everter Device to Aid with Arterial Anastomosis.
AB  - BACKGROUND:  A novel arterial everter device was engineered to simplify
      microvascular coupling of arteries by reliably securing the stiff, muscular wall
      of arteries over coupler pins. We compare microvascular coupling with the everter
      device to manual suturing for arterial anastomoses in a live large animal model.
      MATERIALS AND METHODS:  In this preliminary study, bilateral external femoral
      arteries of five male swine were exposed and sharply divided. Arteries were
      anastomosed using either interrupted sutures (n = 5) or the everter device and
      Synovis Coupler (n = 5). The efficiency in engaging coupler pins, the time taken
      to perform the anastomosis, and vessel patency immediately post-op and at 1-week
      postanastomosis were evaluated. Vessel wall injury and luminal stenosis were
      compared between groups using histomorphometric analyses. RESULTS:  On an
      average, 80% of coupler pins engaged the vessel walls after a single pass of the
      everter. The average time to perform the anastomosis was significantly less when
      using the everter/coupler compared with manual suturing (6:35 minutes versus
      25:09 minutes, p < 0.001). Immediately post-op, 100% patency was observed in both
      groups. At 1 week post-op, four of five (80%) of coupled arteries and all five
      (100%) of hand-sewn arteries were patent. The degree of arterial wall injury,
      neointimal formation, and luminal stenosis for patent arteries were similar
      between groups. CONCLUSIONS:  Successful arterial anastomoses using the everter
      device with the Synovis Coupler was easier and significantly more efficient when
      compared with a standard hand-sewn technique. Both techniques had acceptable
      patency rates and similar effects on the vessel wall and intima.

PMID- 29452443
TI  - Gender Comparison of Medical Student Microsurgical Skills in a Laboratory Model.
AB  - BACKGROUND:  Perceived gender-related differences in surgical skills could limit
      opportunities available for any aspiring surgeon. There should be more available
      literature and logical analysis of these observations. The objective of this
      study is to evaluate the microsurgical skills of male and female medical students
      using a standard scale in the laboratory. METHODS:  This study included medical
      students enrolled in the Kaohsiung Chang Gung Memorial Hospital from 2002 to 2015
      who were evaluated by a senior consultant for their microsurgical skills. A
      standard numeric scale was used to evaluate their suturing technique after basic
      microsurgical training. Differences in the scores between male and female medical
      students were evaluated using statistical analysis. RESULTS:  A total of 578
      medical students were included in the study. There were 393 males (68%) and 185
      females (32%). Using statistical analysis, there is no significant difference in
      the distribution of scores (p-Value = 0.78) and mean scores (p-Value = 0.75)
      between the two groups. CONCLUSIONS:  This study shows that microsurgical skills
      of male and female medical students are similar. Equal opportunities in the
      eventual pursuit of the surgical specialties should be available regardless of
      gender.

PMID- 29452444
TI  - Risk of Venous Thrombosis in Antithrombin Deficiency: A Systematic Review and
      Bayesian Meta-analysis.
AB  - Antithrombin deficiency is a strong risk factor for venous thromboembolism (VTE),
      but the absolute risk of the first and recurrent VTE is unclear. The objective of
      this paper is to establish the absolute risks of the first and recurrent VTE and
      mortality in individuals with antithrombin deficiency. The databases Embase,
      Medline Ovid, Web of Science, the Cochrane Library, and Google Scholar were
      systematically searched for case-control and cohort studies. Bayesian random
      effects meta-analysis was used to calculate odds ratios (ORs), absolute risks,
      and probabilities of ORs being above thresholds. Thirty-five publications were
      included in the systematic review and meta-analysis. Based on 19 studies, OR
      estimates for the first VTE showed a strongly increased risk for antithrombin
      deficient individuals, OR 14.0; 95% credible interval (CrI), 5.5 to 29.0. Based
      on 10 studies, meta-analysis showed that the annual VTE risk was significantly
      higher in antithrombin-deficient than in non-antithrombin-deficient individuals:
      1.2% (95% CrI, 0.8-1.7) versus 0.07% (95% CrI, 0.01-0.14). In prospective
      studies, the annual VTE risk in antithrombin deficient individuals was as high as
      2.3%; 95% CrI, 0.2-6.5%. Data on antithrombin deficiency subtypes are very
      limited for reliable risk-differentiation. The OR for recurrent VTE based on 10
      studies was 2.1; 95% CrI, 0.2 to 4.0. The annual recurrence risk without long
      term anticoagulant therapy based on 4 studies was 8.8% (95% CrI, 4.6-14.1) for
      antithrombin-deficient and 4.3% (95% CrI, 1.5-7.9) for non-antithrombin-deficient
      VTE patients. The probability of the recurrence risk being higher in antithrombin
      deficient patients was 95%. The authors conclude that antithrombin deficient
      individuals have a high annual VTE risk, and a high annual recurrence risk.
      Antithrombin deficient patients with VTE require long-term anticoagulant therapy.

PMID- 29452445
TI  - Suppressive Role of Tissue Factor Pathway Inhibitor-alpha in Platelet-Dependent
      Fibrin Formation under Flow Is Restricted to Low Procoagulant Strength.
AB  - Tissue factor pathway inhibitor-alpha (TFPI-alpha) is a Kunitz-type serine
      protease inhibitor, which suppresses coagulation by inhibiting the tissue factor
      (TF)/factor VIIa complex as well as factor Xa. In static plasma-phospholipid
      systems, TFPI-alpha thus suppresses both factor Xa and thrombin generation. In
      this article, we used a microfluidics approach to investigate how TFPI-alpha
      regulates fibrin clot formation in platelet thrombi at low wall shear rate. We
      therefore hypothesized that the anticoagulant effect of TFPI-alpha in plasma is a
      function of the local procoagulant strength-defined as the magnitude of thrombin
      generation under flow, due to local activities of TF/factor VIIa and factor Xa.
      To test this hypothesis, we modulated local coagulation by microspot coating of
      flow channels with 0 to 100 pM TF/collagen, or by using blood from patients with
      haemophilia A or B. For blood or plasma from healthy subjects, blocking of TFPI
      alpha enhanced fibrin formation, extending from a platelet thrombus, under flow
      only at <2 pM coated TF. This enhancement was paralleled by an increased thrombin
      generation. For mouse plasma, genetic deficiency in TFPI enhanced fibrin
      formation under flow also at 0 pM TF microspots. On the other hand, using blood
      from haemophilia A or B patients, TFPI-alpha antagonism markedly enhanced fibrin
      formation at microspots with up to 100 pM coated TF. We conclude that, under
      flow, TFPI-alpha is capable to antagonize fibrin formation in a manner dependent
      on and restricted by local TF/factor VIIa and factor Xa activities.

PMID- 29452446
TI  - Sjogren's Disease Associated with Severe Retinal Vasculitis and/or Necrotizing
      Scleritis: Two Cases.

PMID- 29452447
TI  - Intense Pulsed Light Eyebrow Epilation and Iris Lesion.

PMID- 29452448
TI  - [Fulminant Panendophthalmitis from Streptococcus pneumoniae after Removal of
      Corneal Suture].

PMID- 29452449
TI  - Efficacy of Natalizumab in Intermediate Uveitis Related to Multiple Sclerosis: A
      Case Report.

PMID- 29452450
TI  - [Cost Comparison of Licensed Intravitreal Therapies for Insufficiently Anti-VEGF
      Responding Fovea Involving Diabetic Macular Edema in Germany].
AB  - BACKGROUND: In the treatment of center-involving diabetic macular edema, despite
      initial therapy with an anti-VEGF compound, an insufficient response may occur.
      Further therapy options include a switch of anti-VEGF products or to
      corticosteroid implants, such as Fluocinolone acetonide or Dexamethasone.
      OBJECTIVES: Firstly, to investigate systematically which evidence-based study
      data are available describing the efficacy of in-label treatments after primary
      anti-VEGF treatment, secondly, to investigate which costs go along for the
      healthcare provider. METHODS: A systematic literature review (SLR) for randomized
      controlled trials (RCT) was performed in Medline and Embase. A short-term cost
      cost model was built in MS Excel with a 3 year time horizon to compare in-label
      intravitreal options Ranibizumab (Lucentis(r)), Aflibercept (Eylea(r)),
      Fluocinolone acetonide implant (Iluvien(r)), and Dexamethasone implant
      (Ozurdex(r)). Cost components comprised of drug and injection costs, optical
      coherence tomography (OCT) procedures, and adverse events such as
      endophthalmitis, IOP-lowering drugs and surgery and cataract surgery. RESULTS: A
      total of 42 publications of 20 RCTs were identified. No study had a clearly
      defined population after first line anti-VEGF treatment, thus no direct efficacy
      comparison was possible. In the short-term cost-cost model total costs were
      17,542 ? for Ranibizumab, 15,896 ? for Aflibercept, 10,826 ? for Fluocinolone
      acetonide implant and 12,365 ? for Dexamethasone implant. For all treatment
      regimens, drug costs were the predominant cost component, followed by injection
      costs (with variations dependent on the specific drug) and OCT costs. In the uni-
      and multivariate sensitivity analyses, the results obtained were robust to
      changes of model inputs. CONCLUSIONS: In summary, the short-term cost-cost
      comparison demonstrates that steroid implants can provide significant cost
      savings versus in-label anti-VEGF treatment for center-involving diabetic macular
      edema. Single application of the long-lasting Fluocinolone acetonide implant is
      the most cost-efficient in-label treatment option.

PMID- 29452451
TI  - Botulinum Toxin for the Treatment of Cyclic Strabismus in Children: Three Case
      Reports.
AB  - Cyclic strabismus is a rare disease of unknown origin. If untreated, it leads to
      manifest strabismus with the risk of amblyopia in children. Treatment is
      generally surgical. Here we report on three children in whom cyclic esotropia was
      successfully treated with one bimedial injection of 5 IU Botox(r). All patients
      remained orthotropic with good stereo functions at the last follow-ups at 16, 11,
      and 8 months. Botulinum toxin offered a minimally invasive treatment option in
      these patients.

PMID- 29452452
TI  - [Effectivity and Safety of a Modified Tip Design in Torsional
      Phacoemulsification].
AB  - BACKGROUND: Torsional mode phacoemulsification results in more effective
      fragmentation of the nucleus due to a different movement of the phacotip. In this
      clinical study, we investigated the influence of a modified tip design and active
      fluidics on the efficacy of phacoemulsification and safety for the corneal
      endothelium. MATERIAL AND METHODS: We conducted a prospective randomized 2 : 1
      study in which 40 patients were operated on with the mini-flared Kelman Tip using
      the Infiniti(r) System (group 1), and 20 patients were operated on with the
      Intrepid(r) Balanced Tip and the Centurion(r) System. We analyzed the
      intraoperative cumulative dissipated energy and also the density of the corneal
      endothelium measured with an endothelial microscope (CEM 530, Nidek) pre- and
      postoperatively. RESULTS: Both groups did not differ preoperatively in age, sex,
      axial length of the globe or corneal endothelium cell density nor cataract
      density (LOCS3). All surgeries were uneventful. The cumulative dissipated energy
      in group 1 (mini-flared Kelman tip, Infiniti System) was 38% higher than in group
      2 (balanced tip, Centurion System; p < 0.05). The endothelial cell loss was 8% in
      group 1 and 10.3% in group 2 (p > 0.05). The cell size (polymegathism) increased
      in both groups significantly with + 37 um in group 1 (p < 0.05) und + 54 um in
      group 2 (p < 0.05). There was no statistically significant difference between
      both groups (p > 0.05). The number of hexagonal cells (pleomorphism) and corneal
      thickness did not differ in both groups either pre- nor postoperatively.
      CONCLUSIONS: Compared to torsional phacoemulsification with a mini-flared Kelman
      Tip and gravity fluidics, torsional phacoemulsification with a modified tip
      design and active fluidics is 38% more effective regarding the cumulative
      dissipated energy. Endothelial cell loss occurs to a similar extend using both
      systems. The postoperative changes in cell size (polymegathism), number of
      hexagonal cells (pleomorphism) and corneal thickness (pachymetry) were similar
      among both systems. We conclude, that the intraoperative stress on the
      endothelium is equivalent with both systems used.

PMID- 29452453
TI  - [Personalized Ophthalmology - Induced Pluripotent Stem Cells for In Vitro
      Modelling of Retinal Degenerative Diseases].
AB  - Today, the search for therapeutic options to treat retinal degeneration often
      relies on an in-depth understanding of the underlying pathological events.
      Alternatively, it is conceivable to search, in an undirected screening approach,
      for chemical compounds affecting disease outcome. For both approaches, there is
      an urgent need for in vitro and, ideally, in vivo disease models that adequately
      reflect the site of pathology. Currently available animal models possess
      limitations as they often develop only defined aspects of disease. Primary cell
      cultures, derived from the posterior pole of the eye, can only be obtained after
      invasive surgery or are available post mortem, but due to rapid cell senescence
      are not suited for long-term analysis. Immortalized retinal cell lines, on the
      other hand, differ in many aspects from native cells. In this situation, a
      promising alternative could arise from induced pluripotent stem cells (iPSCs).
      This cell species can be generated via non-invasive techniques, they are patient
      specific, can be propagated indefinitely, and theoretically can be differentiated
      in all types of retinal cells due to their pluripotent capacities. Importantly,
      the iPSC-derived retinal cells greatly resemble native cells in many
      characteristic traits. In this review we present a selection of established in
      vivo und in vitro models for retinal degenerative disease. We also discuss the
      potential of iPSCs for personalized in vitro modelling and provide an overview of
      existent iPSC-derived cell types of the posterior pole, particularly for cells of
      the retinal pigment epithelium. We finally give an outlook for the potential of
      such cells for basic research in ophthalmology.

PMID- 29452454
TI  - Macular Edema in Childhood Uveitis.
AB  - BACKGROUND: Pediatric uveitis is associated with a high incidence of severe and
      frequently permanent visual loss. This article summarizes the current
      understanding of the disease and the therapeutic options that are available to
      improve treatment outcomes. METHODS: A Medline search spanning the last 10 years
      was undertaken using the key terms "pediatric uveitis" or "childhood uveitis" and
      "macular edema". Articles which appertained to case reports or small case series
      were excluded from consideration, whereas those in which the opinions of experts
      were expressed, as well as reviews, were not. The information contained in these
      latter two forms of publication was particularly valuable, owing to the scarcity
      of prospective clinical data appertaining to the treatment of pediatric uveitis
      associated macular edema. RESULTS: Ten years ago, 34% of children who presented
      with uveitis manifested secondary complications at the time of diagnosis. During
      the ensuing 3 years of treatment, this rose to 86%. Heightening awareness of the
      disease with earlier referrals to expert centers, as well as the advent of
      therapeutic strategies involving anti-TNF agents and intravitreal
      corticosteroids, have led to a decrease in the incidence of legal blindness in
      the affected eyes from 18 - 69% to below 8% during a five-year course of
      treatment. CONCLUSION: Early diagnosis and strict control of inflammatory
      activity have led to a dramatic reduction in the incidence of vision-threatening
      secondary complications. In the majority of cases, it has also been possible to
      resolve cystoid macular edema, which, if insufficiently controlled by systemic
      therapy, usually responds well to intravitreal dexamethasone implants.

PMID- 29452456
TI  - Cutoff for high-sensitivity cardiac troponin T is not arbitrary but according to
      usual clinical practice.

PMID- 29452457
TI  - Perioperative myocardial infarction after heart valve surgery, where are we
      going?

PMID- 29452455
TI  - Complex HuR function in pancreatic cancer cells.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with
      dismal patient outcomes. The underlying core genetic drivers of disease have been
      identified in human tumor specimens and described in genetically engineered mouse
      models. These genetic drivers of PDAC include KRAS signaling, TP53 mutations, and
      genetic loss of the SMAD4 tumor suppressor protein. Beyond the known mutational
      landscape of PDAC genomes, alternative disrupted targets that extend beyond
      conventional genetic mutations have been elusive and understudied in the context
      of PDAC cell therapeutic resistance and survival. This last point is important
      because PDAC tumors have a unique and complex tumor microenvironment that
      includes hypoxic and nutrient-deprived niches that could select for cell
      populations that garner therapeutic resistance, explaining tumor heterogeneity in
      regards to response to different therapies. We and others have embarked in a line
      of investigation focused on the key molecular mechanism of posttranscriptional
      gene regulation that is altered in PDAC cells and supports this pro-survival
      phenotype intrinsic to PDAC cells. Specifically, the key regulator of this
      mechanism is a RNA-binding protein, HuR (ELAVL1), first described in cancer
      nearly two decades ago. Herein, we will provide a brief overview of the work
      demonstrating the importance of this RNA-binding protein in PDAC biology and then
      provide insight into ongoing work developing therapeutic strategies aimed at
      targeting this molecule in PDAC cells. This article is categorized under: RNA in
      Disease and Development > RNA in Disease.

PMID- 29452458
TI  - Working toward an evidence-based cutoff recommendation for myocardial infarction
      detection after cardiac surgery.

PMID- 29452459
TI  - What is the best tool for rescue?

PMID- 29452460
TI  - Outcomes after surgical pulmonary embolectomy for acute submassive and massive
      pulmonary embolism: A single-center experience.
AB  - OBJECTIVES: Ideal treatment strategies for submassive and massive pulmonary
      embolism remain unclear. Recent reports of surgical pulmonary embolectomy have
      demonstrated improved outcomes, but surgical technique and postoperative outcomes
      continue to be refined. The aim of this study is to describe in-hospital survival
      and right ventricular function after surgical pulmonary embolectomy for
      submassive and massive pulmonary embolism with excessive predicted mortality
      (>=5%). METHODS: All patients undergoing surgical pulmonary embolectomy (2011
      2015) were retrospectively reviewed. Patients with pulmonary embolism were
      stratified as submassive, massive without arrest, and massive with arrest.
      Submassive was defined as normotensive with right ventricular dysfunction.
      Massive was defined as prolonged hypotension due to the pulmonary embolism.
      Preoperative demographics, intraoperative variables, and postoperative outcomes
      were compared. RESULTS: A total of 55 patients were identified: 28 as submassive,
      18 as massive without arrest, and 9 as massive with arrest. All patients had a
      right ventricle/left ventricle ratio greater than 1.0. Right ventricular
      dysfunction decreased from moderate preoperatively to none before discharge (P <
      .001). In-hospital and 1-year survival were 93% and 91%, respectively, with 100%
      survival in the submassive group. No patients developed renal failure requiring
      hemodialysis at discharge or had a postoperative stroke. CONCLUSIONS: In this
      single institution experience, surgical pulmonary embolectomy is a safe and
      effective therapy to treat patients with a submassive or massive pulmonary
      embolism. Although survival in this study is higher than previously reported for
      patients treated with medical therapy alone, a prospective trial comparing
      surgical therapy with medical therapy is necessary to further elucidate the role
      of surgical pulmonary embolectomy in the treatment of pulmonary embolism.

PMID- 29452461
TI  - Angiogenesis precedes cardiomyocyte migration in regenerating mammalian hearts.
AB  - OBJECTIVE: Although the mammalian heart's ability to fully regenerate is debated,
      its potential to extensively repair itself is gaining support. We hypothesized
      that heart regeneration relies on rapid angiogenesis to support myocardial
      regrowth and sought to characterize the timeline for angiogenesis and cell
      proliferation in regeneration. METHODS: One-day-old CD-1 mice (P1, N = 60)
      underwent apical resection or sham surgery. Hearts were explanted at serial time
      points from 0 to 30 days postresection and analyzed with immunohistochemistry to
      visualize vessel ingrowth and cardiomyocyte migration into the resected region.
      Proliferating cells were labeled with 5-ethynyl-2'-deoxyuridine injections 12
      hours before explant. 5-Ethynyl-2'-deoxyuridine-positive cells were counted in
      both the apex and remote areas of the heart. Masson's trichrome was used to
      assess fibrosis. RESULTS: By 30 days postresection, hearts regenerated with
      minimal fibrosis. Compared with sham surgery, apical resection stimulated a
      significant increase in proliferation of preexisting cardiomyocytes between 3 and
      11 days after injury. Capillary migration into the apical thrombus was detected
      as early as 2 days postresection, with development of mature arteries by 5 days
      postresection. New vessels became perfused by 5 days postresection as evidenced
      by lectin injection. Vessel density and diameter significantly increased within
      the resected area over 21 days, and vessel ingrowth always preceded cardiomyocyte
      migration, with coalignment of most migrating cardiomyocytes with ingrowing
      vessels. CONCLUSIONS: Endothelial cells migrate into the apical thrombus early
      after resection, develop into functional arteries, and precede cardiomyocyte
      ingrowth during mammalian heart regeneration. This endogenous neonatal response
      emphasizes the importance of expeditious angiogenesis required for neomyogenesis.

PMID- 29452462
TI  - Heart regeneration: The endothelial cell comes first.

PMID- 29452464
TI  - The pitfalls of early mortality as a measure of surgical success.

PMID- 29452463
TI  - Autosomal dominant mannose-binding lectin deficiency is associated with worse
      neurodevelopmental outcomes after cardiac surgery in infants.
AB  - OBJECTIVES: The MBL2 gene is the major genetic determinant of mannose-binding
      lectin (MBL)-an acute phase reactant. Low MBL levels have been associated with
      adverse outcomes in preterm infants. The MBL2Gly54Asp missense variant causes
      autosomal dominant MBL deficiency. We tested the hypothesis that MBL2Gly54Asp is
      associated with worse neurodevelopmental outcomes after cardiac surgery in
      neonates. METHODS: This is an analysis of a previously described cohort of
      patients with nonsyndromic congenital heart disease who underwent cardiac surgery
      with cardiopulmonary bypass before age 6 months (n = 295). Four-year
      neurodevelopment was assessed in 3 domains: Full-Scale Intellectual Quotient, the
      Visual Motor Integration development test, and the Child Behavior Checklist to
      assess behavior problems. The Child Behavior Checklist measured total behavior
      problems, pervasive developmental problems, and internalizing/externalizing
      problems. A multivariable linear regression model, adjusting for confounders, was
      fit. RESULTS: MBL2Gly54Asp was associated with a significantly increased
      covariate-adjusted pervasive developmental problem score (beta = 3.98; P =
      .0025). Sensitivity analyses of the interaction between age at first surgery and
      MBL genotype suggested effect modification for the patients with MBL2Gly54Asp
      (Pinteraction = .039), with the poorest neurodevelopment outcomes occurring in
      children who had surgery earlier in life. CONCLUSIONS: We report the novel
      finding that carriers of MBL2Gly54Asp causing autosomal dominant MBL deficiency
      have increased childhood pervasive developmental problems after cardiac surgery,
      independent of other covariates. Sensitivity analyses suggest that this effect
      may be larger in children who underwent surgery at earlier ages. These data
      support the role of nonsyndromic genetic variation in determining postsurgical
      neurodevelopment-related outcomes in children with congenital heart disease.

PMID- 29452465
TI  - Early mortality is inherently inaccurate as a quality marker for congenital heart
      surgery.

PMID- 29452466
TI  - Tracing the origin, tracking the evolution, and the treatment of the future.

PMID- 29452467
TI  - Is there a benefit to continuing with resection of all sites of disease when
      clinically occult pleural metastases from non-small cell carcinoma are found?

PMID- 29452468
TI  - Direct comparison between video-assisted thoracoscopic surgery and muscle-sparing
      minithoracotomy in the era of minimally invasive thoracic surgery.

PMID- 29452469
TI  - Comparison of outcomes between muscle-sparing thoracotomy and video-assisted
      thoracic surgery in patients with cT1 N0 M0 lung cancer.

PMID- 29452470
TI  - Are we comparing apples and thoracotomies?

PMID- 29452471
TI  - Precise capture of thoracic morbidity and mortality: Essential to the process and
      culture of quality improvement.

PMID- 29452472
TI  - Accurate data capture, essential but only the first step in quality improvement.

PMID- 29452473
TI  - Short-term outcomes do not capture the real value of lung cancer surgery.

PMID- 29452474
TI  - Left versus right.

PMID- 29452475
TI  - Left versus right.

PMID- 29452476
TI  - Oxygen insufflation during 1-lung ventilation.

PMID- 29452477
TI  - Confusion still exists regarding postoperative delirium and its etiology after
      esophagectomy.

PMID- 29452478
TI  - Why consider a paraesophageal hernia giant and a long esophagus short?
      Definitions and results of surgery for paraesophageal hiatal hernias.

PMID- 29452479
TI  - Short esophagus is a disease of the past and the prevention of recurrent hiatal
      hernia is the challenge of the future.

PMID- 29452480
TI  - Paraesophageal hernias: "You say potato, I say potato".

PMID- 29452481
TI  - Notice of Correction.

PMID- 29452482
TI  - 2017 The American Association for Thoracic Surgery Presidential Address: Ancora
      imparo: Always learning.

PMID- 29452483
TI  - Magdi H. Yacoub: Celebrating the AATS Scientific Achievement Award.

PMID- 29452484
TI  - Comparison of patients with multivessel disease treated at centers with and
      without on-site cardiac surgery.
AB  - BACKGROUND: The regional needs and consolidation of cardiac surgery services
      (CSS) result in an increased number of stand-alone interventional cardiology
      units. We aimed to explore the impact of a heart team on the decision making and
      outcomes of patients with multivessel coronary artery disease referred for
      coronary revascularization in stand-alone interventional cardiology units.
      METHODS: This prospective study included 1063 consecutive patients with
      multivessel disease enrolled between January and April 2013 from all 22 hospitals
      in Israel that perform coronary angiography and percutaneous coronary
      intervention (PCI), with or without on-site CSS. RESULTS: Of the 1063 patients,
      487 (46%) underwent coronary artery bypass grafting (CABG) and 576 (54%)
      underwent PCI. A higher proportion of patients underwent PCI in hospitals without
      on-site CSS compared with those with on-site CSS (65% vs 46%; P < .001).
      Furthermore, patients referred to CABG from hospitals without on-site CSS had a
      significantly higher mean SYNTAX score compared with those who underwent CABG in
      centers with on-site CSS (29 vs 26; P = .018). Multivariate logistic regression
      analysis consistently showed that the absence of on-site cardiac surgery and a
      heart team was independently associated with a 2.5-fold increased likelihood for
      predicting the referral of PCI rather than CABG (odds ratio, 2.54; 95% confidence
      interval, 1.8-3.6). CONCLUSIONS: Patients with multivessel coronary artery
      disease treated in centers without on-site cardiac surgery services receive a
      lower rate of appropriate guideline-based intervention with CABG. These findings
      suggest that a heart team approach should be mandatory even in centers with stand
      alone interventional cardiology units.

PMID- 29452485
TI  - Sternotomy extra-anatomic bypass followed by stent-graft extraction.

PMID- 29452486
TI  - There's more than one way to skin this cat.

PMID- 29452487
TI  - When push comes to shove.

PMID- 29452488
TI  - Picosecond Proton Transfer Kinetics in Water Revealed with Ultrafast IR
      Spectroscopy.
AB  - Aqueous proton transport involves the ultrafast interconversion of hydrated
      proton species that are closely linked to the hydrogen bond dynamics of water,
      which has been a long-standing challenge to experiments. In this study, we use
      ultrafast IR spectroscopy to investigate the distinct vibrational transition
      centered at 1750 cm-1 in strong acid solutions, which arises from bending
      vibrations of the hydrated proton complex. Broadband ultrafast two-dimensional IR
      spectroscopy and transient absorption are used to measure vibrational relaxation,
      spectral diffusion, and orientational relaxation dynamics. The hydrated proton
      bend displays fast vibrational relaxation and spectral diffusion timescales of
      200-300 fs; however, the transient absorption anisotropy decays on a remarkably
      long 2.5 ps timescale, which matches the timescale for hydrogen bond
      reorganization in liquid water. These observations are indications that the
      bending vibration of the aqueous proton complex is relatively localized, with an
      orientation that is insensitive to fast hydrogen bonding fluctuations and
      dependent on collective structural relaxation of the liquid to reorient. We
      conclude that the orientational relaxation is a result of proton transfer between
      configurations that are well described by a Zundel-like proton shared between two
      flanking water molecules.

PMID- 29452492
TI  - Treatment patterns and Medicaid spending in comorbid schizophrenia populations:
      once-monthly paliperidone palmitate versus oral atypical antipsychotics.
AB  - OBJECTIVE: To compare treatment patterns and Medicaid spending between
      schizophrenia patients initiating once-monthly paliperidone palmitate (PP1M) and
      oral atypical antipsychotics (OAAs) within four comorbid populations:
      cardiovascular disease (CVD), diabetes, hypertension and obesity. METHODS: Five
      state Medicaid data identified comorbid adults with schizophrenia initiating PP1M
      or OAAs (index) from September 2009 balanced with inverse probability of
      treatment weighting. Chi-squared and t-tests compared index antipsychotic (AP)
      exposure (no gap >90 days) duration, AP polypharmacy, and index AP adherence
      (proportion of days covered >=80%) and persistence (no gap >=60 days) at 12
      months post-index. Linear models with a non-parametric bootstrap procedure
      compared costs. RESULTS: PP1M patients consistently had longer index AP exposure
      (e.g. CVD: 244 vs. 189 days; p < .001) and less AP polypharmacy (e.g. CVD: 21.1%
      vs. 28.1%; p < .001) versus OAA patients. Relative to OAA patients, adherence was
      more likely in PP1M patients with CVD or obesity (e.g. CVD: 28.6% vs. 22.1%; p <
      .001) and less likely for patients with diabetes (22.0% vs. 24.4%; p = .031).
      Persistence was consistently more likely for PP1M versus OAA patients (e.g. CVD:
      49.9% vs. 27.4%; p < .001). Total costs were not significantly different between
      PP1M and OAA patients for any comorbidity. PP1M patients with diabetes,
      hypertension or obesity had higher pharmacy and lower medical costs (all p <
      .05). CONCLUSIONS: Treatment with PP1M versus OAAs may reduce AP polypharmacy and
      increase AP persistence in comorbid patients with schizophrenia, without
      increasing total healthcare costs. Comorbidities are a highly prevalent driver of
      excess mortality in this vulnerable population; thus, future studies should
      specifically address the real-world effectiveness of therapies, including long
      acting injectable therapies (LAIs), for these patients.

PMID- 29452493
TI  - In vitro and in vivo evaluation of cyclodextrin-based nanosponges for enhancing
      oral bioavailability of atorvastatin calcium.
AB  - The aim of this study was to explore the feasibility of complexing the poorly
      water-soluble drug atorvastatin calcium (AC) with beta-cyclodextrin (beta-CD)
      based nanosponges (NS), which offer advantages of improving dissolution rate and
      eventually oral bioavailability. Blank NS were fabricated at first by reacting
      beta-CD with the cross-linker carbonyldiimidazole at different molar ratios (1:2,
      1:4, and 1:8), then NS of highest solubilization extent for AC were complexed
      with AC. AC loaded NS (AC-NS) were characterized for various physicochemical
      properties. Pharmacokinetic, pharmacodynamics and histological finding of AC-NS
      were performed in rats. The prepared AC-NS showed particles size ranged from
      408.7 +/- 12.9 to 423 +/- 15.9 nm while zeta potential values varied from -21.7
      +/- 0.90 to -22.7 +/- 0.85 mV. The loading capacity varied from 17.9 +/- 1.21 to
      34.1 +/- 1.16%. DSC, FT-IR, and PXRD studies confirmed the complexation of AC
      with NS and amorphous state of the drug in the complex. AC-NS displayed a
      biphasic release pattern with increase in the dissolution rate of AC as compared
      to plain AC. Oral administration of AC-NS (1:4 w/w, drug: NS) to rats led to 2.13
      folds increase in the bioavailability as compared to AC suspension.
      Pharmacodynamics studies in rats with fatty liver revealed significant reduction
      (p < .05) in total cholesterol, triglyceride, LDL-C and increased level of
      beneficial HDL-C along with improvement in the associated liver steatosis as
      confirmed through photomicrographs of liver sections. In this study, we confirmed
      that complexation of AC with NS would be a viable approach for improving oral
      bioavailability and in vivo performance of AC.

PMID- 29452499
TI  - Louis Agassiz: Creator of American Science by Christoph Irmscher (2013) Houghton
      Mifflin Harcourt, Boston.

PMID- 29452500
TI  - Preparation of an optimized ciprofloxacin-loaded chitosan nanomicelle with
      enhanced antibacterial activity.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of lipid
      structure on physicochemical properties of chitosan-fatty acid nanomicelles and
      prepare an optimum ciprofloxacin-loaded formulation from these conjugates which
      could enhance the antibacterial effects of drug against some important pathogens
      like P. aeruginosa. SIGNIFICANCE: Nowadays, resistance in infectious diseases is
      a growing worldwide concern. Nanocarriers can increase the therapeutic index and
      consequently reduce the antibiotic resistance. By site-specific delivery of drug,
      the adverse effects of broad-spectrum antibiotics such as ciprofloxacin would be
      reduced. METHODS: Fatty acid grafted chitosan conjugates were synthetized in the
      presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. The effects of fatty
      acid type (stearic acid, palmitic acid, and linoleic acid) on physicochemical
      properties of conjugates were investigated. Ciprofloxacin was encapsulated in
      nanomicelles by thin film hydration method. Also, the preparation process was
      optimized with a central composite design. The antibacterial effect of optimum
      formulation against P. aeruginosa, K. pneumoniae, and S. pneumoniae species was
      determined. RESULTS: All conjugates were synthetized with high yield values and
      the substitution degrees ranged between 2.13 and 35.46%. Ciprofloxacin was
      successfully encapsulated in nanomicelles. The optimum formulation showed high
      drug loading (~ 19%), with particle size of about 260 nm and a sustained release
      profile of ciprofloxacin. The minimum inhibitory concentrations of ciprofloxacin
      in optimum formulation against P. aeruginosa and K. pneumoniae species were 4 and
      2 times lower in comparison with the free drug, respectively. CONCLUSIONS: The
      antibacterial effect of ciprofloxacin was improved by encapsulation of drug in
      chitosan nanomicelles.

PMID- 29452497
TI  - No signal of interactions between influenza vaccines and drugs used for chronic
      diseases: a case-by-case analysis of the vaccine adverse event reporting system
      and vigibase.
AB  - BACKGROUND: An increasing number of reports indicates that vaccines against
      influenza may interact with specific drugs via drug metabolism. To date, actual
      impact of vaccine-drug interactions observed in the real world clinical practice
      has not been investigated. METHODS: From VAERS and VigiBase, we collected Adverse
      Event Following Immunization (AEFI) reports for individuals receiving vaccines
      against influenza recorded as suspect and selected cases where predictable
      toxicity was recorded with oral anticoagulants, antiepileptics and statins (i.e.
      hemorrhages, overdosage and rhabdomyolysis, respectively). We applied AEFI and
      Drug Interaction Probability Scale (DIPS) Algorithms to assess causality of drug
      vaccine interactions. RESULTS: 116 AEFI reports submitted to VAERS and 83 from
      Vigibase were included in our analysis; antiepileptics and statins were related
      to the highest number of indeterminate/consistent (93.7%; 65.3%) and
      possible/probable (50%; 57.7%) cases according to the AEFI and DIPS,
      respectively. The majority of cases occurred within the first week after vaccine
      administration (5-7 days). CONCLUSION: The relative paucity of detected
      interactions does not impact on the benefit of the vaccination against influenza,
      which remains strongly recommended; this does not exclude that closer monitoring
      for selected patients exposed to concomitant chronic pharmacological therapies
      and affected by predisposing factors may be useful.

PMID- 29452502
TI  - Electronic Health Records: A Community Practitioner's Perspective.

PMID- 29452501
TI  - PLWC Podcasts Deliver Oncologist-Approved Information to Patients.

PMID- 29452503
TI  - ASCO 2007 Clinical Practice Guideline Update on the Role of Bisphosphonates in
      Multiple Myeloma: Guideline Summary.

PMID- 29452505
TI  - Building and Maintaining a Referral Base.

PMID- 29452504
TI  - Ovarian Cancer National Alliance: Supporting Action, Education, and Awareness.

PMID- 29452506
TI  - ASCO Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors:
      Cardiac and Pulmonary Late Effects-Review Summary.

PMID- 29452507
TI  - Developing an Effective Oncology Team.

PMID- 29452508
TI  - A 10-Point Billing Office Check-Up.

PMID- 29452509
TI  - Why Volunteer?

PMID- 29452511
TI  - State Affiliate Grant Program.

PMID- 29452510
TI  - ASCO's Advocacy Updates.

PMID- 29452512
TI  - FAQs From the Coding and Reimbursement Hotline: Port Flush, 59 and 25 Modifiers,
      Anticoagulation, and Management.

PMID- 29452513
TI  - Documenting Informed Consent for Chemotherapy.

PMID- 29452514
TI  - Medicare's Hospital Outpatient Prospective Payment System: OPPS 101 (part 1 of
      2).

PMID- 29452515
TI  - Intelligent anticancer drug delivery performances of two poly(N
      isopropylacrylamide)-based magnetite nanohydrogels.
AB  - This article evaluates the anticancer drug delivery performances of two
      nanohydrogels composed of poly(N-isopropylacrylamide-co-itaconic anhydride)
      [P(NIPAAm-co-IA)], poly(ethylene glycol) (PEG), and Fe3O4 nanoparticles. For this
      purpose, the magnetite nanohydrogels (MNHGs) were loaded with doxorubicin
      hydrochloride (DOX) as a universal anticancer drug. The morphologies and magnetic
      properties of the DOX-loaded MNHGs were investigated using transmission electron
      microscopy (TEM) and vibrating-sample magnetometer (VSM), respectively. The sizes
      and zeta potentials (xi) of the MNHGs and their corresponding DOX-loaded
      nanosystems were also investigated. The DOX-loaded MNHGs showed the highest drug
      release values at condition of 41  degrees C and pH 5.3. The drug-loaded MNHGs at
      physiological condition (pH 7.4 and 37  degrees C) exhibited negligible drug
      release values. In vitro cytotoxic effects of the DOX-loaded MNHGs were
      extensively evaluated through the assessing survival rate of HeLa cells using the
      MTT assay, and there in vitro cellular uptake into the mentioned cell line were
      examined using fluorescent microscopy and fluorescence-activated cell sorting
      (FACS) flow cytometry analyses. As the results, the DOX-loaded MNHG1 exhibited
      higher anticancer drug delivery performance in the terms of cytotoxic effect and
      in vitro cellular uptake. Thus, the developed MNHG1 can be considered as a
      promising de novo drug delivery system, in part due to its pH and thermal
      responsive drug release behavior as well as proper magnetite character toward
      targeted drug delivery.

PMID- 29452517
TI  - A decade of the Clinical Trials Transformation Initiative: What have we
      accomplished? What have we learned?
AB  - The Clinical Trials Transformation Initiative reflects on 10 years of working to
      improve the quality and efficiency of clinical trials. This article highlights
      many of the Clinical Trials Transformation Initiative's accomplishments and
      offers examples of the impact that the Clinical Trials Transformation Initiative
      has had on the clinical trials enterprise. After conducting more than 25 projects
      and issuing recommendations for specific strategies to improve the design and
      execution of clinical trials, some common themes and lessons learned have
      emerged. Lessons include the importance of engaging many stakeholders, advanced
      planning to address critical issues, discontinuation of non-value added
      practices, and new opportunities presented by technology. Through its work, the
      Clinical Trials Transformation Initiative has also derived some operational best
      practices for conducting collaborative, multi-stakeholder projects covering
      project selection, project team dynamics and execution, and multi-stakeholder
      meetings and team discussions. Through these initiatives, the Clinical Trials
      Transformation Initiative has helped move the needle toward needed change in the
      clinical trials enterprise that has directly impacted stakeholders and patients
      alike.

PMID- 29452518
TI  - The Clinical Trials Transformation Initiative: Looking back, looking forward.

PMID- 29452519
TI  - Patient engagement in clinical trials: The Clinical Trials Transformation
      Initiative's leadership from theory to practical implementation.
AB  - Patient engagement is an increasingly important aspect of successful clinical
      trials. Over the past decade, as patient group involvement in clinical trials has
      continued to increase and diversify, the Clinical Trials Transformation
      Initiative has not only recognized the crucial role patients play in improving
      the clinical trial enterprise but also made a deep commitment to help grow and
      shape the emerging field of patient engagement. This article describes the
      evolution of patient engagement including the origins of the patient engagement
      movement; barriers to successful engagement and remaining challenges to full and
      valuable collaboration between patient groups and trial sponsors; and Clinical
      Trials Transformation Initiative's role in influencing the field through
      organizational practices, formal project work and resulting recommendations, and
      external advocacy efforts.

PMID- 29452521
TI  - Clinical trial quality: From supervision to collaboration and beyond.
AB  - Over the past decade, clinical trial quality has evolved from an after-the-fact,
      reactive activity to one focused on the important work of evidence generation
      from well-designed trials. This article explores the role the Clinical Trials
      Transformation Initiative has played in advancing quality as a core element of
      clinical trial design, through project work that initially focused on monitoring
      but evolved into a holistic, prospective, and comprehensive quality by design
      approach to clinical trial design and conduct.

PMID- 29452520
TI  - The Clinical Trials Transformation Initiative: Methodology supporting the
      mission.
AB  - The mission of the Clinical Trials Transformation Initiative, a public-private
      partnership co-founded by the U.S. Food and Drug Administration and Duke
      University, is to develop and drive adoption of practices that will increase the
      quality and efficiency of clinical trials. The Clinical Trials Transformation
      Initiative works collaboratively with key stakeholders, implements "fit-for
      purpose" evidence-gathering projects, and develops actionable recommendations and
      tools to address the challenges faced by the clinical trials enterprise. In
      pursuit of its mission, The Clinical Trials Transformation Initiative follows an
      innovative and collaborative, five-step methodology: (1) state the problem and
      identify impediments to research, (2) gather evidence to identify gaps and
      barriers, (3) explore results by analyzing and interpreting findings, (4)
      finalize solutions by developing recommendations and tools, and (5) drive
      adoption through disseminating and implementing recommendations and tools. This
      article describes each step of the Clinical Trials Transformation Initiative's
      methodology, with a specific focus on describing the evidence-gathering
      activities.

PMID- 29452522
TI  - The evolution of clinical trials: Can we address the challenges of the future?
AB  - The authors describe key challenges facing the clinical trials community and
      propose solutions to these issues, including the role the Clinical Trials
      Transformation Initiative can play in addressing these issues. Specifically, the
      authors reflect on clinical trial globalization and the harmonization of
      frameworks and requirements across regions; the challenges associated with
      balancing the desire for external validity, pragmatic trials, and precision
      medicine; clinical trial transparency; and operational complexity and the expense
      of clinical trials. By addressing these challenges, future clinical trials will
      be more feasible, relevant, and credible, and support both the continuing
      altruistic contributions of patients and the collection of more meaningful data.

PMID- 29452523
TI  - Oncology Tomorrowland (With Apologies to Walt Disney).

PMID- 29452524
TI  - Look Good ... Feel Better Helps People Battling Cancer Help Themselves.

PMID- 29452525
TI  - Institutional Review Boards and Safety Interventions.
AB  - Monitoring and quality assurance in a medically valid way is essential, even in a
      small community setting.

PMID- 29452526
TI  - Resources Update.

PMID- 29452527
TI  - Communication: What Do Patients Want and Need?

PMID- 29452528
TI  - Principles of Safe Practice Using an Oncology EHR System for Chemotherapy
      Ordering, Preparation, and Administration, Part 2 of 2.
AB  - Integrating electronic health records into the oncology office, while taking into
      consideration the principles of electronic health record usage, is a great way to
      improve the chemotherapy ordering and administration process.

PMID- 29452529
TI  - Institute for Healthcare Improvement Community-Based Cancer Care Studies.
AB  - The Institute for Healthcare Improvement undertook a series of 90-day studies to
      see which practices provide coordinated care informed by physical and
      psychosocial health.

PMID- 29452531
TI  - The ASCO Cancer Foundation.

PMID- 29452530
TI  - Medicare Contracting Reform.
AB  - Having a single Medicare administrative contractor, or MAC, lets providers rely
      on one entity for coverage and reimbursement policies, claims processing issues,
      and general provider information.

PMID- 29452532
TI  - State Affiliate Grant Program.

PMID- 29452533
TI  - Serum CA125 in combination with ferritin improves diagnostic accuracy for
      epithelial ovarian cancer.
AB  - INTRODUCTION: CA125 has poor sensitivity and low specificity for detecting early
      ovarian cancer. Serum ferritin is elevated in many malignancies. We evaluated the
      performance of ferritin alone and in combination with CA125 as a diagnostic tool
      to detect epithelial ovarian cancer (EOC). METHODS: CA125 and ferritin were
      detected in the serum of 50 healthy control (HC), 50 women with benign
      gynaecological conditions and 124 women with EOC. The relationship between serum
      ferritin and CA125 and each of the clinicopathological parameters was assessed,
      and their diagnostic accuracy for discriminating ovarian cancer determined.
      RESULTS: Serum ferritin and CA125 were higher in patients with EOC compared to
      HCs and patients with benign conditions (both p < 0.001). There was no
      relationship between levels of ferritin and CA125. Both ferritin and CA125
      discriminated HC from EOC (p < 0.05), but ferritin showed better diagnostic
      accuracy than CA125 (p = 0.048). Ferritin was superior to CA125 in discrimination
      early EOC (p = 0.002), but in advanced stages, CA125 was superior (p = 0.026). A
      combination of ferritin and CA125 marginally increases the diagnostic accuracy to
      discriminate EOC from HCs. CONCLUSION: Ferritin discriminates between HCs and EOC
      patients, especially in early stage disease. The combination of serum ferritin
      and CA125 provides the higher diagnostic accuracy to screen for EOC. Serum
      ferritin could serve as an EOC biomarker to complement the standard CA125 test.

PMID- 29452537
TI  - Current Procedural Terminology 2009 Coding Changes for Drug Administration.

PMID- 29452538
TI  - A Guide to Web Site Development for the Community Oncology Practice.

PMID- 29452534
TI  - Co-culture of human bone marrow mesenchymal stem cells and macrophages attenuates
      lipopolysaccharide-induced inflammation in human corneal epithelial cells.
AB  - Dry eye syndrome (DES) is considered as an ocular surface inflammatory disease.
      Previous studies have shown inflammation plays an important role in the
      progression and onset of DES. Co-culture of human bone marrow mesenchymal stem
      cells (HBMSCs) and macrophages showed immunomodulatory effects via regulation of
      cytokine regulation. Thus, the aim of this study was to investigate the effect of
      the interaction of these cells on in vitro DES model. The conditioned media (CM)
      from macrophages, HBMSCs, and HBMSCs + macrophages were treated to human corneal
      epithelial cells, which showed significant reduction in IL-1alpha and IL-1beta
      expression levels in HBMSCs + macrophages group. Moreover, the IL-1 Receptor
      Antagonist (IL-1RA) was highly expressed in the CM from the HBMSCs + macrophages
      group. Wounded eyes of mice were treated with IL-1RA at 0-100 ng/mL for 16 h, the
      wound size was reduced. The results of this study might lead to the
      identification of new therapeutic targets for DES.

PMID- 29452539
TI  - Informed Consent for Chemotherapy: ASCO Member Resources.

PMID- 29452541
TI  - State Affiliate Management Options.

PMID- 29452540
TI  - Striving to Better Serve and Respond to Members.

PMID- 29452543
TI  - View and Order Updated Patient Materials From Cancer.Net, ASCO's Patient
      Information Website.

PMID- 29452542
TI  - Effective Staff Management.

PMID- 29452544
TI  - Can combined blood neutrophil to lymphocyte ratio and C-reactive protein be used
      for diagnosis of spontaneous bacterial peritonitis?
AB  - BACKGROUND AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is diagnosed by
      the presence of >=250 polymorphonuclear neutrophils (PMN)/mm3 in the ascites and
      the absence of surgically treatable cause of intra-abdominal infection. Blood
      neutrophil lymphocytic ratio (NLR) is an inexpensive and simple test for
      inflammation. C-reactive protein (CRP) is an inflammatory marker used for the
      diagnosis and follow-up of many diseases and morbidities. We aimed to evaluate
      the clinical utility of combined blood NLR and CRP as a non-invasive test for SBP
      diagnosis. METHODS: Blood NLR was calculated, and CRP value determined in 180
      cirrhotic patients with ascites (126 with and 54 without SBP). Sensitivity and
      specificity of combined blood NLR and CRP values for SBP diagnosis were estimated
      by receiver operator characteristic curve. RESULTS: Both blood NLR and CRP values
      were significantly higher in SBP (p < 0.001). For SBP diagnosis, a blood NLR of
      >2.89 had a sensitivity 80.3% and specificity 88.9%. CRP >11.3 mg/dL had a
      sensitivity 88.9% and specificity 92.6%. In logistic regression analysis,
      combined blood NLR and CRP had a sensitivity 95.1% and specificity 96.3% at the
      same cut off values. CONCLUSIONS: Combined NLR and CRP could be used as a novel,
      simple, low-cost, non-invasive test for SBP diagnosis.

PMID- 29452545
TI  - Sentinel Lymph Node Biopsy for Melanoma: American Society of Clinical Oncology
      and Society of Surgical Oncology Joint Clinical Practice Guideline.

PMID- 29452546
TI  - Appropriate Chemotherapy Dosing for Obese Adult Patients With Cancer: American
      Society of Clinical Oncology Clinical Practice Guideline.

PMID- 29452548
TI  - Oncology Clinical Pathways: A Form of Governance?

PMID- 29452547
TI  - Potential value of circulating microRNA-126 and microRNA-210 as biomarkers for
      type 2 diabetes with coronary artery disease.
AB  - BACKGROUND: Macrovascular complications are the main cause of morbidity and
      mortality among the diabetic patients. MicroRNAs (miRNAs), a family of small non
      coding RNAs, play vital roles in the regulation of blood glucose level and the
      concurrent cardiovascular complications of type 2 diabetes. We hypothesized that
      plasma miR-126 and miR-210 are linked to coronary artery disease (CAD) in these
      diabetes patients. METHODS: Fasting blood samples were collected from 20 healthy
      volunteers and 100 patients with diabetes (54 patients without CAD and 46
      patients with CAD). Plasma miR-126 and miR-210 expressions were assessed by
      quantitative real time PCR. Specificity and sensitivity of miR-126 and miR-210 to
      discriminate CAD with diabetes was determined by receiver operating
      characteristic curve analysis. Correlations between miR-126 and miR-210 and
      studied characteristics in diabetes patients with and without CAD were compared.
      RESULTS: Plasma relative expressions of miR-126 and miR-210 were 0.38 +/- 0.03
      and 5.3 +/- 0.56 in diabetes alone vs. 0.08 +/- 0.03 and 21.44 +/- 0.97 in
      diabetes with CAD, respectively (both p < 0.0001). Levels of miR-126 and miR-210
      significantly correlated with certain glycemic and lipid indices. The miRNAs
      significantly discriminated between diabetes with and without CAD at cut-off
      values of 0.055 (sensitivity 91.3%, specificity 100%) for miR-126 and of 17.59
      (sensitivity 93.5%, specificity 100%) for miR-210. CONCLUSION: Plasma miR-126 and
      miR-210 levels may be biomarkers for diabetes with or without CAD.

PMID- 29452549
TI  - Characterizing Potentially Preventable Cancer- and Chronic Disease-Related
      Emergency Department Use in the Year After Treatment Initiation: A Regional
      Study.
AB  - PURPOSE: As new quality metrics and interventions for potentially preventable
      emergency department (ED) visits are implemented, we sought to compare methods
      for evaluating the prevalence and costs of potentially preventable ED visits that
      were related to cancer and chronic disease among a commercially insured oncology
      population in the year after treatment initiation. METHODS: We linked SEER
      records in western Washington from 2011 to 2016 with claims from two commercial
      insurers. The study included patients who were diagnosed with a solid tumor and
      tracked ED utilization for 1 year after the start of chemotherapy or radiation.
      Cancer symptoms from the Centers for Medicare & Medicaid Services metric and a
      patient-reported outcome intervention were labeled potentially preventable
      (PpCancer). Prevention Quality Indicators of the Agency for Healthcare Research
      and Quality were labeled potentially preventable-chronic disease (PpChronic). We
      reported the primary diagnosis, all diagnosis field coding (1 to 10), and 2016
      adjusted reimbursements. RESULTS: Of 5,853 eligible patients, 27% had at least
      one ED visit, which yielded 2,400 total visits. Using primary diagnosis coding,
      49.8% of ED visits had a PpCancer diagnosis, whereas 3.2% had a PpChronic
      diagnosis. Considering all diagnosis fields, 45.0%, 9.4%, and 18.5% included a
      PpCancer only, a PpChronic only, and both a PpCancer and a PpChronic diagnosis,
      respectively. The median reimbursement per visit was $735 (interquartile ratio,
      $194 to $1,549). CONCLUSION: The prevalence of potentially preventable ED visits
      was generally high, but varied depending on the diagnosis code fields and the
      group of codes considered. Future research is needed to understand the complex
      landscape of potentially preventable ED visits and measures to improve value in
      cancer care delivery.

PMID- 29452551
TI  - NASN: 50 Years of Leadership.

PMID- 29452550
TI  - An Eye on Vision: 20 Questions About Vision Screening and Eye Health.
AB  - Current evidence-based and best practice vision screening and eye health
      approaches, tools, and procedures are the result of revised national guidelines
      in the past 3 years and advances in research during the last 16 years. To help
      the busy school nurse with little time to keep up with changes in children's
      vision practices and a growing body of literature, the National Center for
      Children's Vision and Eye Health at Prevent Blindness is providing answers to 20
      questions received most often from the field. Question topics are: (1) arranging
      the screening environment, (2) occluders to cover the eyes during vision
      screening, (3) optotype-based screening at distance, (4) optotype-based screening
      at near, (5) instrument-based screening, (6) muscle imbalance screening, (7)
      referrals, and (8) vision screening certification.

PMID- 29452553
TI  - Sexual Health Education in Schools: Position Statement.

PMID- 29452552
TI  - Caring for the Student With Asthma at School: What's Out There to Help the School
      Nurse?
AB  - Asthma is a high impact health issue in the school setting. One in 10 children
      comes to school with asthma, and it is the leading cause for absenteeism causing
      13.8 million missed school days each year. Where can the school nurse turn for
      help? The following article provides evidence-based resources to assist school
      nurses in caring for their students with asthma.

PMID- 29452554
TI  - What Does the Evidence Say Is Best for Your Student? CLUE #3: Appraise.
AB  - School nurses are often faced with various requests from parents, teachers, and
      even healthcare providers. How do you know what requests should be honored? What
      does the current evidence indicate? This article is the third in a series of
      articles outlining the steps of evidence-based practice. The article explains and
      provides tips for accomplishing the third step: Appraise the evidence. Appraising
      the evidence means better understanding what the literature says and how strong
      the evidence is. This is an important step in evidence-based school nursing
      practice.

PMID- 29452555
TI  - Letter to the Editor.

PMID- 29452556
TI  - Use of a Prescription-Assistance Program for Medically Uninsured Patients With
      Cancer: Case Study of a Public Hospital Experience in New York State.
AB  - PURPOSE: With the advances in early detection, prevention, and treatment of some
      cancers, mortality rates in the United States have been consistently falling.
      However, with these successes have come substantial increases in the cost of
      cancer care. Antineoplastics are the leading class in hospital drug expenditures.
      Cancer treatments are causing a serious financial burden for patients, families,
      hospitals, and society at large, especially for those who are uninsured.
      Prescription assistance programs (PAPs) are offered by pharmaceutical
      manufacturers to provide medications at no out-of-pocket cost to medically
      indigent patients. To assist the Cancer Care Center at Nassau University Medical
      Center (NUMC) with drug costs for chemotherapies, a clinical pharmacist-managed
      PAP was implemented to procure chemotherapy medications from pharmaceutical
      manufacturers. NUMC is a safety-net teaching hospital in suburban New York. It
      serves mostly an indigent population, and its Level I trauma center has more than
      77,000 emergency department visits per year. METHODS: We observed all patients
      requiring assistance with chemotherapy who enrolled in PAPs from January 1, 2011,
      through December 31, 2012. The total number of visits in the clinic over 24
      months was 9,405. Individuals potentially eligible for the PAP were identified by
      oncologists. Patients received a referral to the PAP when they mentioned to
      office personnel that they had difficulty obtaining medications or expressed
      financial concerns related to management. RESULTS: The clinical pharmacist spent
      the majority of his time assisting uninsured individuals, working with charity
      pools from the drug manufacturers, and obtaining medications through the PAP. The
      program served 341 patients in 2011 and 579 patients in 2012. Medications
      obtained for these patients included both oral and parenteral chemotherapy drugs
      and antiemetics. The total cost savings of the medications was $908,944.11 in
      2011 and $1,715,538.37 in 2012. In 2012, a total of 783 prescriptions were
      processed, and 775 were approved by the manufacturers (98.9%). CONCLUSION: PAPs
      provide a valuable safety net to ensure that uninsured patients with cancer
      receive needed prescription medications. The rising cost of health care and the
      high proportion of indigent patients have financially burdened the hospital. For
      the pharmacy department, this has resulted in a lack of compensation for
      pharmaceuticals dispensed to indigent patients. A pharmacy-based program to
      procure free medications for uninsured patients with cancer has helped to defray
      the expenses of the Cancer Care Center in providing care at NUMC, increased
      patient compliance with chemotherapy protocols, and allowed many patients to
      receive the treatments they otherwise would not have been able to afford.

PMID- 29452557
TI  - Michigan Oncology Medical Home Demonstration Project: First-Year Results.
AB  - PURPOSE: The Michigan Oncology Medical Home Demonstration Project (MOMHDP) is an
      innovative multipractice oncology medical home model, supported by payment
      reform. Sponsored by Priority Health, Physician Resource Management, and ION
      Solutions, MOMHDP includes four oncology practices and 29 physicians. METHODS:
      Oncology practices used existing technologies, with MOMHDP providing evidence
      based treatment guideline selection and compliance tracking, automated physician
      order entry, a patient portal, symptom management/standardized nurse triage, and
      advance care planning. To support changes in care and administrative models and
      to focus on quality, MOMHDP modifies provider payments. The program replaces the
      average sales price payment methodology with a drug acquisition reimbursement
      plus a care management fee, calculated to increase total drug reimbursement.
      Additionally, it reimburses for chemotherapy and treatment planning and advance
      care planning consultation. There is also a shared savings opportunity. MOMHDP
      will be enhanced in its second year to include a survivorship program, patient
      distress screening, imaging guidelines, and standardized patient satisfaction
      surveys. Priority Health patients receiving chemotherapy for a cancer diagnosis
      were recruited to the program. Results for this group were compared with a
      control group of patients from a prior period. RESULTS: In addition to the
      financial results, the project also accomplished the following: (1) adherence to
      practice-selected guidelines, (2) institution of advance care planning, (3)
      effective and standardized symptom management; and (4) payment reform.
      CONCLUSION: We have identified a number of critical success factors: strong
      payer/provider collaboration built on trust through transparent use and cost
      data; timing of clinical standardization must come from the practices, so they
      can effectively absorb new approaches; having comprehensive, written program
      documentation and consistently applied training facilitate practice
      understanding; existing, off-the-shelf technologies help control costs;
      independent clinical, administrative, and technical coordination improves
      provider/payer collaboration; everything takes longer than anticipated, including
      practice commitment, contracting, and technology implementation. Practices are
      willing to take on clinical standardization with payment reform. Neither practice
      size nor technology platform variation was a barrier to participation or success
      in the project. These results represent preliminary reporting from the first
      multipractice oncology medical home in the United States, to our knowledge, with
      payer support that includes payment reform. The results are promising, and the
      concept warrants further study, review, and reporting. [Table: see text].

PMID- 29452558
TI  - Achieving the Meaningful Use Standard: A Model for Implementing Change Within
      Medical Practices.
AB  - PURPOSE: Change management in medical practices is often an uphill battle. Lack
      of agreement on standards, ineffective leadership, inertia, inconsistent access
      to data, and inability to clearly define and communicate the benefits of change
      represent significant barriers to success. In 2009, the Health Information
      Technology for Economic and Clinical Health (HITECH) Act created the meaningful
      use (MU) incentive program administered through the Centers for Medicare and
      Medicaid Services (CMS). To earn financial incentive payments, eligible
      physicians adopt certified electronic health record (EHR) technology and use it
      to meet specified objectives. In response, leadership of the US Oncology Network
      launched an MU initiative designed to create a comprehensive system of tools,
      education, performance feedback, and support that would facilitate successful
      achievement of the MU standards. METHODS: The EHR used by the majority of network
      physicians was modified according to the MU specifications, and EHR certification
      was obtained. Baseline compliance data were measured for each of the MU standards
      and for each of the eligible physicians. Physician and staff workflow processes
      necessary for consistent data input and compliance were outlined for each
      standard. Each practice identified one or more staff members who would act as MU
      leads. Training modules were developed for the MU leads as well as for
      physicians, mid-level providers, nurses, medical assistants, and office staff. An
      MU measurement tool was created, designed to target areas for MU process
      improvement and automate reporting. Data were updated and verified weekly to
      provide timely feedback to practices, including individual physician detail and
      links to individual patient records. RESULTS: A total of 943 practitioners within
      the US Oncology Network met eligibility criteria for the MU program. At baseline,
      compliance with each MU standard ranged from 0% (clinical summaries) to 100%
      (computerized order entry). In many cases, data were simply not being entered
      into the EHR. Time from program launch to first submission of MU attestation was
      18 months. As of March 2013, 781 practitioners (83%) had achieved the MU
      standards. In comparison, CMS reported that 44% of all eligible physicians and
      26% of hematologists and oncologists had successfully achieved Medicare MU
      standards and received payment. CONCLUSION: Successful change management in
      medical practices can be accomplished through a comprehensive system of
      leadership, education, support, timely feedback of data, and clearly defined
      incentives. Incentives alone may be far less effective.

PMID- 29452559
TI  - Improving Medical Oncology Quality Through Peer-to-Peer Consultation.
AB  - PURPOSE: This study describes how the use of peer-to-peer (P2P) physician
      consultation improves medical oncology care quality by preventing non-evidence
      based and potentially morbid chemotherapy treatments. New Century Health (NCH)
      has adapted a physician audit and feedback model to strengthen adherence to
      clinical guidelines. In the NCH oncology program, P2P consultation complements
      clinical pathways and an online prior authorization platform. Payers are adopting
      the use of clinical pathways as a management strategy for managing costs and
      improving quality. Managing medical oncology is a complex process, because
      evidence evolves rapidly, and almost one third of chemotherapy is prescribed off
      label. The use of prior authorization, combined with standardized protocols for
      patients with specific cancer diagnoses, is one way for payers to reduce
      unnecessary treatment variation. [Table: see text] Methods: NCH completed a
      retrospective analysis of the chemotherapy treatment requests (CTRs) submitted by
      payers' oncologists for prior authorization between January and December 2012.
      The objectives of the clinical impact analysis were to measure the CTR
      disposition rate, identify the CTR intervention rate resulting from P2P
      consultation, and identify the types of drug triggering the interventions.
      RESULTS: Analysis of the 13,078 CTRs associated with the 1,116 unique Medicare
      and commercial patients of a national health plan determined that CTRs
      voluntarily withdrawn or recommended adverse determination (RAD; ie, NCH
      recommendation to member's health plan to not authorize treatment as requested;
      after review of health plan policy and compendia, NCH was not able to resolve
      provider's request through P2P consultation and could not recommend approval of
      treatment plan as requested, therefore recommending denial of request) by the
      submitting physician as a result of a P2P consultation with an NCH board
      certified oncologist comprised 11.6% of all CTRs. Further analysis identified the
      types of medication associated with the 1,521 CTRs withdrawn/RAD as a consequence
      of P2P consultation. Interventions on chemotherapeutic medications and supportive
      care were evenly distributed at 51.2% and 48.8%, respectively. Interventions on
      medications that had received US Food and Drug Administration approval within the
      last 2 years (initial approval or for new indications) represented 12.1%. [Table:
      see text] Conclusion: Using P2P consultation to complement a pathway-driven prior
      authorization process improves medical oncology quality. In addition, P2P
      consultation can be an effective collaborative physician engagement strategy by
      supporting oncologists with critical clinical information and mitigating concerns
      about pathway implementation and about payer involvement in drug use management.

PMID- 29452560
TI  - Health Care Efficiencies: Consolidation and Alternative Models vs. Health Care
      and Antitrust Regulation - Irreconcilable Differences?
AB  - Despite the U.S. substantially outspending peer high income nations with almost
      18% of GDP dedicated to health care, on any number of statistical measurements
      from life expectancy to birth rates to chronic disease, 1 the U.S. achieves
      inferior health outcomes. In short, Americans receive a very disappointing return
      on investment on their health care dollars, causing economic and social strain. 2
      Accordingly, the debates rage on: what is the top driver of health care spending?
      Among the culprits: poor communication and coordination among disparate
      providers, paperwork required by payors and regulations, well-intentioned
      physicians overprescribing treatments, drugs and devices, outright fraud and
      abuse, and medical malpractice litigation. Fundamentally, what is the best way to
      reduce U.S. health care spending, while improving the patient experience of care
      in terms of quality and satisfaction, and driving better patient health outcomes?
      Mergers, partnerships, and consolidation in the health care industry, new care
      delivery models like Accountable Care Organizations and integrated care systems,
      bundled payments, information technology, innovation through new drugs and new
      medical devices, or some combination of the foregoing? More importantly, recent
      ambitious reform efforts fall short of a cohesive approach, leaving fundamental
      internal inconsistencies across divergent arms of the federal government, raising
      the issue of whether the U.S. health care system can drive sufficient
      efficiencies within the current health care and antitrust regulatory
      environments. While debate rages on Capitol Hill over "repeal and replace," only
      limited attention has been directed toward reforming the current "fee-for
      service" model pursuant to which providers are paid for volume of care rather
      than quality or outcomes. Indeed, both the Patient Protection and Affordable Care
      Act ("ACA") 3 and proposals for its replacement focus primarily on the reach and
      cost of providing coverage for health care, rather than specifics for the
      delivery of health care. 4 With the U.S. expenditures on health care producing
      inferior results, experts see consolidation and alternatives to fee-for-service
      as fundamental to reducing costs. 5 Integrating care coordination and delivery
      and increasing scale to drive efficiencies allows organizations to benefit from
      shared savings and relationships with payors and vendors. 6 Deloitte forecasts
      that, by 2024, the current health system landscape-which includes roughly 80
      national health systems, 275 regional systems, 130 academic medical centers, and
      1,300 small community systems-will morph into just over 900 multi-hospital
      systems. 7 Even though health care market and payment reforms encourage
      organizations to consolidate and integrate, innovators must proceed with extreme
      caution. Health care organizations attempting to drive efficiencies and bring
      down costs through mergers may run afoul of numerous federal and state laws and
      regulations. 8 Calls for updates or leniency in these laws are growing, including
      the possible recognition of an "Obamacare defense" to antitrust restrictions 9
      and speculation that laws restricting physicians from having financial
      relationships will be repealed, ostensibly to allow sharing of the rewards reaped
      from coordinated care. 10 In the meantime, however, absent specific waivers or
      exemptions, all the usual rules and regulations apply, including antitrust
      constraints, 11 physician self-referral 12 and anti-kickback laws and
      regulations, 13 state fraud and abuse restrictions, 14 and more. In short, a
      maelstrom of conflicting political prescriptions, health care regulations, and
      antitrust restrictions undermine the ability of innovators to achieve
      efficiencies through joint ventures, transactions, innovative models, and other
      structures. This article first considers the conflicting positions taken by the
      United States government with respect to achieving efficiencies in health care
      under the ACA and alternative delivery models, on the one hand, and health care
      regulatory enforcement and antitrust enforcement, on the other. At almost a fifth
      of the U.S. economy, 15 health care arguably has grown ungovernable, exceeding
      the ability of any one law or branch of government to create or implement
      coherent reform. Indeed, the article posits that although the ACA reformed and
      expanded access to health care, it failed to transform the way health care is
      delivered beyond limited "demonstration projects", leaving fee-for-service
      intact. Nonetheless, even with limited rather than revolutionary goals, the ACA
      still lacks sufficient authority across disparate branches of government to
      achieve its stated goals. The article then examines the conflicting positions of
      the various United States regulatory schemes and enforcement agencies governing
      health care, and whether they can be reconciled with the stated goal of the
      government, often referred to as the "Triple Aim": 16 improving quality of care,
      improving population health, and lowering health care costs. It examines
      fundamental, systemic challenges to achieving the "Triple Aim": longstanding
      health care regulatory laws that impede adoption of innovative delivery systems
      beyond their current "demonstration project" status, and antitrust enforcement
      that promotes waste and duplication in densely populated areas, while preventing
      necessary consolidation to more efficiently reach rural areas. The article
      concludes with recommendations for promoting efficiency through modest
      reconciliation of the conflicting goals and regulations in health care.

PMID- 29452561
TI  - Recent Case Developments.

PMID- 29452562
TI  - Deciphering the Sunshine Act: Transparency Regulation and Financial Conflicts in
      Health Care.
AB  - The Physician Payments Sunshine Act ("Sunshine Act"), enacted to address
      financial conflicts in health care, is the first comprehensive federal
      legislation mandating public reporting of payments between drug companies, device
      manufacturers, and medicine. This article analyzes the Sunshine Act's uneven
      record, exploring how the law serves as an intriguing example of the uncertain
      case for transparency regulation in health care. The Sunshine Act's bumpy rollout
      demonstrates that commanding transparency through legislation can be arduous
      because of considerable implementation challenges. Capturing all the relevant
      information about financial relationships and reporting it with sufficient
      contextual and comparative data has proven disappointingly difficult. In
      addition, the law suffers from uncertainty and poor design as to the intended
      audience. Indeed, there is strong reason to believe that it will not
      significantly impact decision-making of primary recipients like patients. Yet the
      Sunshine Act nonetheless retains important and perhaps underappreciated value.
      From the almost four years of information generated, we have learned that
      industry-medicine financial ties vary significantly by physician specialty, and
      somewhat by physician gender. In many medical fields the distribution of top
      dollar payments tends to be heavily skewed to a few recipients, all of which have
      important implications for optimal management of financial conflicts and for
      health policy more generally. Accordingly, the Sunshine Act's greatest potential
      is not guiding decisions of individual patients or physicians, but its downstream
      effects. This Article traces how secondary audiences, such as regulators,
      watchdogs, and counsel are already starting to make productive use of Sunshine
      Act information. Public reporting has, for example, made more feasible linking
      industry payment information with Medicare reimbursement data. As a result,
      policymakers can more closely examine correlations between industry spending
      directed at individual physicians and their prescribing and referral decisions.
      Moreover, savvy counsel are recognizing that Sunshine Act information provides
      explosive evidence in private civil litigation and this Article explores the
      first wave of cases.

PMID- 29452563
TI  - Code Red: The Essential Yet Neglected Role of Emergency Care in Health Law
      Reform.
AB  - The United States' health care system is mired in uncertainty. Public opinion on
      the Patient Protection and Affordable Care Act ("ACA") is undeniably mixed and
      politicized. The individual mandate, tax subsidies, and Medicaid expansion
      dominate the discussion. This Article argues that the ACA and reform discourse
      have given short shrift to a more static problem: the law of emergency care. The
      Emergency Medical Treatment and Active Labor Act of 1986 ("EMTALA") requires most
      hospitals to screen patients for emergency medical conditions and provide
      stabilizing treatment regardless of patients' insurance status or ability to pay.
      Remarkably, this law strengthened the health safety net in a country that has no
      universal health care. But it is an unfunded mandate that responded to the
      problem of emergency care in a flawed fashion and contributed to the supposed
      "free rider" problem that the ACA attempted to cure. But the ACA has also not
      been effective at addressing the issue of emergency care. The ACA's architects
      reduced funding for hospitals that serve a disproportionate percentage of the
      medically indigent but did not anticipate the Supreme Court's ruling in NFIB v.
      Sebelius, which made Medicaid expansion optional. Public and non-profit hospitals
      now face a scenario of less funding and potentially higher emergency room
      utilization due to continued uninsurance or underinsurance. Alternatives to the
      ACA have been insufficiently attentive to the importance of emergency care in our
      health system. This Article contends that any proposal that does not seriously
      consider EMTALA is incomplete and bound to produce some of the same problems that
      have dogged the American health care system for the past few decades. Moreover,
      the Article shows how notions of race, citizenship, and deservingness have
      filtered into this health care trajectory, and in the context of reform, have the
      potential to exacerbate existing health inequality. The paper concludes with
      normative suggestions on how to the mitigate EMTALA's problems in ways that might
      improve population health.

PMID- 29452564
TI  - When Consent Does Not Help: Challenges to Women's Access to a Vaginal Birth After
      Cesarean Section and the Limitations of the Informed Consent Doctrine.
AB  - Pregnant women with a prior cesarean delivery face challenges in accessing a
      vaginal birth due to both hospital and provider preferences and practices.
      Although the doctrine of informed consent secures women's reproductive rights, it
      is not a viable legal remedy. Instead, women should champion increased maternity
      related education and transparency as well as medical malpractice reform to
      increase the desired access.

PMID- 29452565
TI  - Serum vitamin C levels modulate the lifespan and endoplasmic reticulum stress
      response pathways in mice synthesizing a nonfunctional mutant WRN protein.
AB  - Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ
      family DNA helicase (WRN). Mice lacking part of the helicase domain of the WRN
      ortholog exhibit several phenotypic features of WS. In this study, we generated a
      Wrn mutant line that, like humans, relies entirely on dietary sources of vitamin
      C (ascorbate) to survive, by crossing them to mice that lack the gulonolactone
      oxidase enzyme required for ascorbate synthesis. In the presence of 0.01%
      ascorbate (w/v) in drinking water, double-mutant mice exhibited a severe
      reduction in lifespan, small size, sterility, osteopenia, and metabolic profiles
      different from wild-type (WT) mice. Although increasing the dose of ascorbate to
      0.4% improved dramatically the phenotypes of double-mutant mice, the metabolic
      and cytokine profiles were different from age-matched WT mice. Finally, double
      mutant mice treated with 0.01% ascorbate revealed a permanent activation of all
      the 3 branches of the ER stress response pathways due to a severe chronic
      oxidative stress in the ER compartment. In addition, markers associated with the
      ubiquitin-proteasome-dependent ER-associated degradation pathway were increased.
      Augmenting the dose of ascorbate reversed the activation of this pathway to WT
      levels rendering this pathway a potential therapeutic target in WS.-Aumailley,
      L., Dubois, M. J., Brennan, T. A., Garand, C., Paquet, E. R., Pignolo, R. J.,
      Marette, A., Lebel, M. Serum vitamin C levels modulate the lifespan and
      endoplasmic reticulum stress response pathways in mice synthesizing a
      nonfunctional mutant WRN protein.

PMID- 29452567
TI  - A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and
      inflammation.
AB  - Angiotensin II (Ang-II)-induced hypertension is associated with accelerated
      thrombus formation in arterioles and leukocyte recruitment in venules. The
      mechanisms that underlie the prothrombotic and proinflammatory responses to
      chronic Ang-II administration remain poorly understood. We evaluated the role of
      CD40/CD40 ligand (CD40L) signaling in Ang-II-mediated microvascular responses and
      assessed whether and how soluble CD40L (sCD40L) contributes to this response.
      Intravital video microscopy was performed to analyze leukocyte recruitment and
      dihydrorhodamine-123 oxidation in postcapillary venules. Thrombus formation in
      cremaster muscle arterioles was induced by using the light/dye endothelial cell
      injury model. Wild-type (WT), CD40-/-, and CD40L-/- mice received Ang-II for 14 d
      via osmotic minipumps. Some mice were treated with either recombinant sCD40L or
      the VLA5 (very late antigen 5; alpha5beta1) antagonist, ATN-161. Our results
      demonstrate that CD40-/-, CD40L-/-, and WT mice that were treated with ATN-161
      were protected against the thrombotic and inflammatory effects of Ang-II
      infusion. Infusion of sCD40L into CD40-/- or CD40L-/- mice restored the
      prothrombotic effect of Ang-II infusion. Mice that were treated with ATN-161 and
      infused with sCD40L were protected against accelerated thrombosis. Collectively,
      these novel findings suggest that the mechanisms that underlie Ang-II-dependent
      thrombotic and inflammatory responses link to the signaling of CD40L via both
      CD40 and VLA5.-Senchenkova, E. Y., Russell, J., Vital, S. A., Yildirim, A., Orr,
      A. W., Granger, D. N., Gavins, F. N. E. A critical role for both CD40 and VLA5 in
      angiotensin II-mediated thrombosis and inflammation.

PMID- 29452566
TI  - Near-tetraploid cancer cells show chromosome instability triggered by replication
      stress and exhibit enhanced invasiveness.
AB  - A considerable proportion of tumors exhibit aneuploid karyotypes, likely
      resulting from the progressive loss of chromosomes after whole-genome
      duplication. Here, by using isogenic diploid and near-tetraploid (4N) single-cell
      derived clones from the same parental cell lines, we aimed at exploring how
      polyploidization affects cellular functions and how tetraploidy generates
      chromosome instability. Gene expression profiling in 4N clones revealed a
      significant enrichment of transcripts involved in cell cycle and DNA replication.
      Increased levels of replication stress in 4N cells resulted in DNA damage,
      impaired proliferation caused by a cell cycle delay during S phase, and higher
      sensitivity to S phase checkpoint inhibitors. In fact, increased levels of
      replication stress were also observed in nontransformed, proliferative
      posttetraploid RPE1 cells. Additionally, replication stress promoted higher
      levels of intercellular genomic heterogeneity and ongoing genomic instability,
      which could be explained by high rates of mitotic defects, and was alleviated by
      the supplementation of exogenous nucleosides. Finally, our data found that 4N
      cancer cells displayed increased migratory and invasive capacity, both in vitro
      and in primary colorectal tumors, indicating that tetraploidy can promote
      aggressive cancer cell behavior.-Wangsa, D., Quintanilla, I., Torabi, K., Vila
      Casadesus, M., Ercilla, A., Klus, G., Yuce, Z., Galofre, C., Cuatrecasas, M.,
      Lozano, J. J., Agell, N., Cimini, D., Castells, A., Ried, T., Camps, J. Near
      tetraploid cancer cells show chromosome instability triggered by replication
      stress and exhibit enhanced invasiveness.

PMID- 29452568
TI  - Primary cilia-regulated transcriptome in the renal collecting duct.
AB  - Renal tubular cells respond to mechanical stimuli generated by urinary flow to
      regulate the activity and transcript abundance of important genes for ion
      handling, cellular homeostasis, and proper renal development. The primary cilium,
      a mechanosensory organelle, is postulated to regulate this mRNA response. The aim
      of this study is to reveal the transcriptome changes of tubular epithelia in
      response to fluid flow and determine the role of primary cilia in this process.
      Inner-medullary collecting duct (CD) cells were subjected to either static or
      physiologically relevant fluid flow (~0.6 dyn/cm2). RNA-sequencing analysis of
      ciliated cells subjected to fluid flow showed up-regulation of 1379 genes and
      down-regulation of 1294 genes compared with static control cells. Strikingly,
      only 54 of these genes were identified as gene candidates sensitive to primary
      cilia sensing of fluid flow, of which 16 were linked to ion or water transport
      pathways in the CD. Validation by quantitative real-time PCR revealed that only
      the expression of transferrin receptor, which is involved in iron transport; and
      tribbles pseudokinase 3, which is involved in insulin signaling, were
      unequivocally regulated by primary cilia sensing of fluid flow. This study shows
      that the involvement of primary cilia in ion transport in the collecting duct is
      exceptionally specific.-Mohammed, S. G., Arjona, F. J., Verschuren, E. H. J.,
      Bakey, Z., Alkema, W., van Hijum, S., Schmidts, M., Bindels, R. J. M., Hoenderop,
      J. G. J. Primary cilia-regulated transcriptome in the renal collecting duct.

PMID- 29452570
TI  - S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.
AB  - Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate
      (S1P), and it participates in several physiologic processes by activating
      different S1P receptors (S1PRs). However, its functions in the nervous system
      remain largely unclear. We explored the important role of SPNS2 in the process of
      retinal morphogenesis using a spns2-deficient rat model. In the absence of the
      functional SPNS2 transporter, we observed progressively aggravating laminar
      disorganization of the epithelium at the postnatal stage of retinal development.
      Disrupted cell polarity, delayed cell-cycle exit of retinal progenitor cells, and
      insufficient migration of newborn neurons were proposed in this study as
      potential mechanisms accounting for this structural disorder. In addition, we
      analyzed the expression profiles of spns2 and s1prs, and proposed that SPNS2
      regulated retinal morphogenesis by establishing the S1P level in the eye and
      activating S1PR3 signaling. These data indicate that SPNS2 is indispensable for
      normal retinal morphogenesis and provide new insights on the role of S1P in the
      developing retina using an established in vivo model.-Fang, C., Bian, G., Ren,
      P., Xiang, J., Song, J., Yu, C., Zhang, Q., Liu, L., Chen, K., Liu, F., Zhang,
      K., Wu, C., Sun, R., Hu, D., Ju, G., Wang, J. S1P transporter SPNS2 regulates
      proper postnatal retinal morphogenesis.

PMID- 29452569
TI  - Up-regulation of SFTPB expression and attenuation of acute lung injury by
      pulmonary epithelial cell-specific NAMPT knockdown.
AB  - Although a deficiency of surfactant protein B (SFTPB) has been associated with
      lung injury, SFTPB expression has not yet been linked with nicotinamide
      phosphoribosyltransferase (NAMPT), a potential biomarker of acute lung injury
      (ALI). The effects of Nampt in the pulmonary epithelial cell on both SFTPB
      expression and lung inflammation were investigated in a LPS-induced ALI mouse
      model. Pulmonary epithelial cell-specific knockdown of Nampt gene expression,
      achieved by the crossing of Nampt gene exon 2 floxed mice with mice expressing
      epithelial-specific transgene Cre or by the use of epithelial-specific expression
      of anti-Nampt antibody cDNA, significantly attenuated LPS-induced ALI. Knockdown
      of Nampt expression was accompanied by lower levels of bronchoalveolar lavage
      (BAL) neutrophil infiltrates, total protein and TNF-alpha levels, as well as
      lower lung injury scores. Notably, Nampt knockdown was also associated with
      significantly increased BAL SFTPB levels relative to the wild-type control mice.
      Down-regulation of NAMPT increased the expression of SFTPB and rescued TNF-alpha
      induced inhibition of SFTPB, whereas overexpression of NAMPT inhibited SFTPB
      expression in both H441 and A549 cells. Inhibition of NAMPT up-regulated SFTPB
      expression by enhancing histone acetylation to increase its transcription.
      Additional data indicated that these effects were mainly mediated by NAMPT
      nonenzymatic function via the JNK pathway. This study shows that pulmonary
      epithelial cell-specific knockdown of NAMPT expression attenuated ALI, in part,
      via up-regulation of SFTPB expression. Thus, epithelial cell-specific knockdown
      of Nampt may be a potential new and viable therapeutic modality to ALI.-Bi, G.,
      Wu, L., Huang, P., Islam, S., Heruth, D. P., Zhang, L. Q., Li, D.-Y., Sampath,
      V., Huang, W., Simon, B. A., Easley, R. B., Ye, S. Q. Up-regulation of SFTPB
      expression and attenuation of acute lung injury by pulmonary epithelial cell
      specific NAMPT knockdown.

PMID- 29452572
TI  - As We Continue to Drift Into a Totalitarian Medical System: A View of a Country
      Boy.

PMID- 29452573
TI  - The effect of Metformin treatment in obese insulin-resistant patients with
      euthyroid goiter.
AB  - Objective The study's objective was to evaluate the thyroid parameters in obese
      insulin-resistant patients with euthyroid diffuse or nodular goiter, following
      Metformin treatment. Patients and methods The study was experimental, open, and
      prospective. Fifty-three patients aged 18-68 were enrolled for two years. Obese
      insulin-resistant patients (cut-off Homeostasis-Model-Assessment of Insulin
      Resistance-HOMA-IR >= 2.5) with euthyroid nodular/diffuse goiter were included.
      Subjects with diabetes, hypo-/hyper-thyroidism, autoimmune thyroiditis,
      psychiatric disorders, liver or heart failure were excluded. Patients were
      randomly assigned to one of the following treatment: Metformin 1000 mg/day +
      Levothyroxine 25 MUg/day (M + LT4 group) and only Levothyroxine 25 MUg/day (LT4
      group). Thyroid and metabolic parameters' evolution was investigated over six
      months. Results The two groups were comparable at baseline (p >= 0.10). TSH,
      waist/hip ratio (WHR), visceral fat thickness (VFT), insulin, and HOMA-IR
      decreased significantly more in M + LT4 group compared to LT4 group. TSH decrease
      correlated with WHR reduction (p = 0.002) only in M + LT4 group. Moreover, the
      multivariate regression analysis revealed that insulin's and HOMA-IR levels'
      decrease was an independent factor associated with FT4's increase (p = 0.031, p =
      0.033) just in M + LT4 group. No other independent association between the
      evolution (Delta) of TSH, thyroid volume (TTV), thyroid nodules-maximum diameter
      (TN-MD), and metabolic parameters was found. In addition, no significant
      threshold between groups was reached when DeltaFT4, DeltaTTV, DeltaTN-MD were
      compared (p > 0.07), although their significant improvement was recorded between
      the baseline and the follow-up moment in each group (p < 0.003). Conclusion
      Metformin added to obese insulin-resistant patients treated with Levothyroxine
      for diffuse/nodular goiter determined a significant decrease in TSH and metabolic
      parameters, compared to those treated with Levothyroxine alone, but no
      significant difference regarding thyroid morphology after 6 months.

PMID- 29452574
TI  - Association of Helicobacter pylori and protozoal parasites in patients with
      chronic diarrhoea.
AB  - Introduction An association of Helicobacter pylori and common protozoal parasites
      in patients with abdominal discomfort and chronic diarrhoea is unclear and may be
      pathological. Materials and methods One hundred and sixty-one patients with
      diarrhoea were compared to 114 age and sex matched controls. Stool samples were
      examined by microscopy and DNA extracted for PCR with specific primers for H.
      pylori and protozoal parasites Blastocystis sp., Entamoeba sp. (Entamoeba
      histolytica, Entamoeba dispar and Entamoeba moshkovskii) and Giardia duodenalis
      (G. duodenalis). Results There was a marked difference in the presence of
      parasites between patients and controls: no parasite 42/75%, one parasite 42/15%,
      two or more parasites 16/10%, respectively (p < 0.001). Patients with diarrhoea
      were more likely to be infected with Blastocystis sp (p < 0.001), E. histolytica
      (p = 0.027) and E moshkovskii (p = 0.003). There was no difference in the
      frequency of H. pylori (p = 0.528), G duodenalis (p = 0.697) or E dispar (p =
      0.425). Thirty-three patients and 27 controls had H. pylori infection. Of these,
      22 patients and 6 controls were infected with Blastocystis sp (p = 0.001), 6
      patients and no controls were infected with E. histolytica (p = 0.02), whilst 7
      patents and 9 controls were infected with E dispar (p = 0.292). Conclusion In
      this population, diarrhoea is linked to infection with Blastocystis sp, E.
      histolytica and E moshkoviskii. In H. pylori infection, diarrhoea is linked to
      Blastocystis sp and E. histolytica infection. These associations may be linked
      pathogenically.

PMID- 29452575
TI  - A machine learning approach to detect changes in gait parameters following a
      fatiguing occupational task.
AB  - The purpose of this study is to provide a method for classifying non-fatigued vs.
      fatigued states following manual material handling. A method of template matching
      pattern recognition for feature extraction ($1 Recognizer) along with the support
      vector machine model for classification were applied on the kinematics of gait
      cycles segmented by our stepwise search-based segmentation algorithm. A single
      inertial measurement unit on the ankle was used, providing a minimally intrusive
      and inexpensive tool for monitoring. The classifier distinguished between states
      using distance-based scores from the recogniser and the step duration. The
      results of fatigue detection showed an accuracy of 90% across data from 20
      recruited subjects. This method utilises the minimum amount of data and features
      from only one low-cost sensor to reliably classify the state of fatigue induced
      by a realistic manufacturing task using a simple machine learning algorithm that
      can be extended to real-time fatigue monitoring as a future technology to be
      employed in the manufacturing facilities. Practitioner Summary: We examined the
      use of a wearable sensor for the detection of fatigue-related changes in gait
      based on a simulated manual material handling task. Classification based on foot
      acceleration and position trajectories resulted in 90% accuracy. This method
      provides a practical framework for predicting realistic levels of fatigue.

PMID- 29452576
TI  - Assessing retention in care after 12 months of the Pediatric Development Clinic
      implementation in rural Rwanda: a retrospective cohort study.
AB  - BACKGROUND: In Africa, a high proportion of children are at risk for
      developmental delay. Early interventions are known to improve outcomes, but they
      are not routinely available. The Rwandan Ministry of Health with Partners In
      Health/Inshuti Mu Buzima created the Pediatric Development Clinic (PDC) model for
      providing interdisciplinary developmental care for high-risk infants in rural
      settings. As retention for chronic care has proven challenging in many settings,
      this study assesses factors related to retention to care after 12 months of
      clinic enrollment. METHODS: This study describes a retrospective cohort of
      children enrolled for 12 months in the PDC program in Southern Kayonza district
      between April 2014-March 2015. We reviewed routinely collected data from
      electronic medical records and patient charts. We described patient
      characteristics and the proportion of patients retained, died, transferred out or
      lost to follow up (LTFU) at 12 months. We used Fisher's exact test and
      multivariable logistic regression to identify factors associated with retention
      in care. RESULTS: 228 children enrolled in PDC from 1 April 2014-31 March 2015,
      with prematurity/low birth weight (62.2%) and hypoxic ischemic encephalopathy
      (34.5%) as the most frequent referral diagnoses. 64.5% of children were retained
      in care and 32.5% were LTFU after 12 months. In the unadjusted analysis, we found
      male sex (p = 0.189), having more children at home (p = 0.027), health facility
      of first visit (p = 0.006), having a PDC in the nearest health facility (p =
      0.136), referral in second six months of PDC operation (p = 0.006), and social
      support to be associated (100%, p < 0.001) with retention after 12 months. In
      adjusted analysis, referral in second six months of PDC operation (Odds Ratio
      (OR) 2.56, 95% CI 1.36, 4.80) was associated with increased retention, and being
      diagnosed with more complex conditions (trisomy 21, cleft lip/palate,
      hydrocephalus, other developmental delay) was associated with LTFU (OR 0.34, 95%
      CI 0.15, 0.76). As 100% of those receiving social support were retained in care,
      this was not able to be assessed in adjusted analysis. CONCLUSIONS: PDC retention
      in care is encouraging. Provision of social assistance and decentralization of
      the program are major components of the delivery of services related to retention
      in care.

PMID- 29452577
TI  - Polymerase delta-interacting protein 2 deficiency protects against blood-brain
      barrier permeability in the ischemic brain.
AB  - BACKGROUND: Polymerase delta-interacting protein 2 (Poldip2) is a multifunctional
      protein that regulates vascular extracellular matrix composition and matrix
      metalloproteinase (MMP) activity. The blood-brain barrier (BBB) is a dynamic
      system assembled by endothelial cells, basal lamina, and perivascular astrocytes,
      raising the possibility that Poldip2 may be involved in maintaining its
      structure. We investigated the role of Poldip2 in the late BBB permeability
      induced by cerebral ischemia. METHODS: Transient middle cerebral artery occlusion
      (tMCAO) was induced in Poldip2+/+ and Poldip2+/- mice. The volume of the ischemic
      lesion was measured in triphenyltetrazolium chloride-stained sections. BBB
      breakdown was evaluated by Evans blue dye extravasation. Poldip2 protein
      expression was evaluated by western blotting. RT-PCR, zymography, and ELISAs were
      used to measure mRNA levels, activity, and protein levels of cytokines and MMPs.
      Cultured astrocytes were transfected with Poldip2 siRNA, and mRNA levels of
      cytokines were evaluated as well as IkappaBalpha protein degradation. RESULTS:
      Cerebral ischemia induced the expression of Poldip2. Compared to Poldip2+/+ mice,
      Poldip2+/- animals exhibited decreased Evans blue dye extravasation and improved
      survival 24 h following stroke. Poldip2 expression was upregulated in astrocytes
      exposed to oxygen and glucose deprivation (OGD) and siRNA-mediated downregulation
      of Poldip2 abrogated OGD-induced IL-6 and TNF-alpha expression. In addition,
      siRNA against Poldip2 inhibited TNF-alpha-induced IkappaBalpha degradation. TNF
      alpha, IL-6, MCP-1, VEGF, and MMP expression induced by cerebral ischemia was
      abrogated in Poldip2+/- mice. The protective effect of Poldip2 depletion on the
      increased permeability of the BBB was partially reversed by systemic
      administration of TNF-alpha. CONCLUSIONS: Poldip2 is upregulated following
      ischemic stroke and mediates the breakdown of the BBB by increasing cerebral
      cytokine production and MMP activation. Therefore, Poldip2 appears to be a
      promising novel target for the development of therapeutic strategies to prevent
      the development of cerebral edema in the ischemic brain.

PMID- 29452578
TI  - Clinical and genetic study of 20 patients from China with Cornelia de Lange
      syndrome.
AB  - BACKGROUND: Cornelia de Lange syndrome (CdLS) is a rare congenital syndrome with
      no racial difference. The objective of this study is to report the clinical
      characteristics and genetic study of 20 CdLS cases from China. METHODS: This is
      an observational study. Suspected patients were referred for further
      confirmation, clinical treatment, and genetic testing under voluntary condition.
      Demographic data and family history, data of clinical manifestations including
      facial dysmorphism and developmental delay of each patient were collected.
      Chromosomal analysis and NIPBL/SMC1A/SMC3 gene mutational analysis were carried
      out by PCR, reverse transcription PCR direct sequencing in the probands, and SNP
      array to detect the genome-wide copy number variations. RESULTS: Twenty CdLS
      cases from China were included in this study. Facial dysmorphisms, feeding
      difficulties, and developmental delay were the major clinical manifestations.
      Seven patients underwent gene mutation tests. Both the SMC1A and SMC3 gene
      mutation tests were negative in all. A heterozygous mutation in exon 20 of the
      NIPBL gene in proband 2, and a heterozygous mutation in intron 38 of the NIPBL
      gene in proband 3 were found in 1 patient, and RT-PCR revealed a splicing
      mutation in exon 38, generating both normal transcript and an aberrant
      alternatively spliced transcript with exon 38 deletion. CONCLUSIONS: Clinical
      manifestations of CdLS patients from China are similar to those in the other
      countries. Heterozygous mutations of NIPBL gene were found.

PMID- 29452579
TI  - Reliability of diagnosis and clinical efficacy of visceral osteopathy: a
      systematic review.
AB  - BACKGROUND: In 2010, the World Health Organization published benchmarks for
      training in osteopathy in which osteopathic visceral techniques are included. The
      purpose of this study was to identify and critically appraise the scientific
      literature concerning the reliability of diagnosis and the clinical efficacy of
      techniques used in visceral osteopathy. METHODS: Databases MEDLINE, OSTMED.DR,
      the Cochrane Library, Osteopathic Research Web, Google Scholar, Journal of
      American Osteopathic Association (JAOA) website, International Journal of
      Osteopathic Medicine (IJOM) website, and the catalog of Academie d'osteopathie de
      France website were searched through December 2017. Only inter-rater reliability
      studies including at least two raters or the intra-rater reliability studies
      including at least two assessments by the same rater were included. For efficacy
      studies, only randomized-controlled-trials (RCT) or crossover studies on
      unhealthy subjects (any condition, duration and outcome) were included. Risk of
      bias was determined using a modified version of the quality appraisal tool for
      studies of diagnostic reliability (QAREL) in reliability studies. For the
      efficacy studies, the Cochrane risk of bias tool was used to assess their
      methodological design. Two authors performed data extraction and analysis.
      RESULTS: Eight reliability studies and six efficacy studies were included. The
      analysis of reliability studies shows that the diagnostic techniques used in
      visceral osteopathy are unreliable. Regarding efficacy studies, the least biased
      study shows no significant difference for the main outcome. The main risks of
      bias found in the included studies were due to the absence of blinding of the
      examiners, an unsuitable statistical method or an absence of primary study
      outcome. CONCLUSIONS: The results of the systematic review lead us to conclude
      that well-conducted and sound evidence on the reliability and the efficacy of
      techniques in visceral osteopathy is absent. TRIAL REGISTRATION: The review is
      registered PROSPERO 12th of December 2016. Registration number is CRD4201605286 .

PMID- 29452581
TI  - Prospective observational study on assessing the hemodynamic relevance of patent
      ductus arteriosus with frequency domain near-infrared spectroscopy.
AB  - BACKGROUND: What constitutes a hemodynamically relevant patent ductus arteriosus
      (hrPDA) in preterm infants is unclear. Different clinical and echocardiographic
      parameters are used, but a gold standard definition is lacking. Our objective was
      to evaluate associations between regional cerebral tissue oxygen saturation
      (rcStO2), fraction of tissue oxygen extraction (rcFtO2E) measured by frequency
      domain near-infrared spectroscopy (fd-NIRS) and their correlation to
      echocardiographic, Doppler-ultrasound, and clinical parameters in preterm infants
      with and without a hrPDA. METHODS: In this prospective observational study, 22
      infants < 1500 g (mean [+/- SD]: gestational age 28.6 [+/-1.8] weeks, birth
      weight 1076 [+/-284] g, median (interquartile range) postnatal age at measurement
      7.6 (4.6-12.9) d) with a clinical suspicion of hrPDA were analysed. Twelve
      infants had left-to-right shunt through PDA, and in 6 of these the PDA was
      classified as hrPDA based on pre-defined clinical and echocardiographic criteria.
      fd-NIRS, echocardiographic and Doppler-ultrasound examinations were performed.
      After identification of blood hemoglobin (Hb) as confounding factor, rcStO2 and
      rcFtO2E were corrected for this effect. RESULTS: Overall mean +/- standard
      deviation (normalised to a median Hb of 13.8 mg/dl) was 57 +/-5% for rcStO2 and
      0.39 +/-0.05 for rcFtO2E. Comparing no-hrPDA with hrPDA infants, there were no
      significant differences in mean rcStO2 (58 +/-5% vs. 54 +/-5%; p = .102), but in
      mean rcFtO2E (0.38 +/-0.05 vs. 0.43 +/-0.05; p = .038). Echocardiographic
      parameter and Doppler indices did not correlate with cerebral oxygenation.
      CONCLUSION: Oxygen transport capacity of the blood may confound NIRS data
      interpretation. Cerebral oxygenation determined by fd-NIRS provided additional
      information for PDA treatment decisions not offered by routine investigations.
      Whether indicating PDA therapy based on echocardiography complemented by data on
      cerebral oxygenation results in better outcomes should be investigated in future
      studies.

PMID- 29452580
TI  - Measuring integrated HIV DNA ex vivo and in vitro provides insights about how
      reservoirs are formed and maintained.
AB  - The identification of the most appropriate marker to measure reservoir size has
      been a great challenge for the HIV field. Quantitative viral outgrowth assay
      (QVOA), the reference standard to quantify the amount of replication-competent
      virus, has several limitations, as it is laborious, expensive, and unable to
      robustly reactivate every single integrated provirus. PCR-based assays have been
      developed as an easier, cheaper and less error-prone alternative to QVOA, but
      also have limitations. Historically, measuring integrated HIV DNA has provided
      insights about how reservoirs are formed and maintained. In the 1990s, measuring
      integrated HIV DNA was instrumental in understanding that a subset of resting CD4
      T cells containing integrated HIV DNA were the major source of replication
      competent virus. Follow-up studies have further characterized the phenotype of
      these cells containing integrated HIV DNA, as well as shown the correlation
      between the integration levels and clinical parameters, such as duration of
      infection, CD4 count and viral load. Integrated HIV DNA correlates with total HIV
      measures and with QVOA. The integration assay has several limitations. First, it
      largely overestimates the reservoir size, as both defective and replication
      competent proviruses are detected. Since defective proviruses are the majority in
      patients on ART, it follows that the number of proviruses capable of reactivating
      and releasing new virions is significantly smaller than the number of integrated
      proviruses. Second, in patients on ART clonal expansion could theoretically lead
      to the preferential amplification of proviruses close to an Alu sequence though
      longitudinal studies have not captured this effect. Proviral sequencing combined
      with integration measures is probably the best estimate of reservoir size, but it
      is expensive, time-consuming and requires considerable bioinformatics expertise.
      All these reasons limit its use on a large scale. Herein, we review the utility
      of measuring HIV integration and suggest combining it with sequencing and total
      HIV measurements can provide insights that underlie reservoir maintenance.

PMID- 29452582
TI  - To what extent can behaviour change techniques be identified within an adaptable
      implementation package for primary care? A prospective directed content analysis.
AB  - BACKGROUND: Interpreting evaluations of complex interventions can be difficult
      without sufficient description of key intervention content. We aimed to develop
      an implementation package for primary care which could be delivered using
      typically available resources and could be adapted to target determinants of
      behaviour for each of four quality indicators: diabetes control, blood pressure
      control, anticoagulation for atrial fibrillation and risky prescribing. We
      describe the development and prospective verification of behaviour change
      techniques (BCTs) embedded within the adaptable implementation packages. METHODS:
      We used an over-lapping multi-staged process. We identified evidence-based,
      candidate delivery mechanisms-mainly audit and feedback, educational outreach and
      computerised prompts and reminders. We drew upon interviews with primary care
      professionals using the Theoretical Domains Framework to explore likely
      determinants of adherence to quality indicators. We linked determinants to
      candidate BCTs. With input from stakeholder panels, we prioritised likely
      determinants and intervention content prior to piloting the implementation
      packages. Our content analysis assessed the extent to which embedded BCTs could
      be identified within the packages and compared them across the delivery
      mechanisms and four quality indicators. RESULTS: Each implementation package
      included at least 27 out of 30 potentially applicable BCTs representing 15 of 16
      BCT categories. Whilst 23 BCTs were shared across all four implementation
      packages (e.g. BCTs relating to feedback and comparing behaviour), some BCTs were
      unique to certain delivery mechanisms (e.g. 'graded tasks' and 'problem solving'
      for educational outreach). BCTs addressing the determinants 'environmental
      context' and 'social and professional roles' (e.g. 'restructuring the social and
      'physical environment' and 'adding objects to the environment') were indicator
      specific. We found it challenging to operationalise BCTs targeting 'environmental
      context', 'social influences' and 'social and professional roles' within our
      chosen delivery mechanisms. CONCLUSION: We have demonstrated a transparent
      process for selecting, operationalising and verifying the BCT content in
      implementation packages adapted to target four quality indicators in primary
      care. There was considerable overlap in BCTs identified across the four
      indicators suggesting core BCTs can be embedded and verified within delivery
      mechanisms commonly available to primary care. Whilst feedback reports can
      include a wide range of BCTs, computerised prompts can deliver BCTs at the time
      of decision making, and educational outreach can allow for flexibility and
      individual tailoring in delivery.

PMID- 29452583
TI  - Does rituximab improve clinical outcomes of patients with thyroid-associated
      ophthalmopathy? A systematic review and meta-analysis.
AB  - BACKGROUND: The current therapies of thyroid-associated ophthalmopathy (TAO) were
      still a challenging matter. In this study, we aimed to contrast the impact of
      before- after rituximab (RTX) therapy in the patients with TAO. METHODS: We
      searched the PubMed, EMBASE, and SCOPUS databases for articles published up to
      July 3, 2017. Fixed- or random-effects meta-analysis was used to provide pooled
      estimates of standard mean difference (SMD) both the primary outcome from
      clinical activity score (CAS), and secondary outcomes from thyrotropin receptor
      antibody (TRAb), proptosis, thyroid stimulating hormone (TSH), and interleukin-6
      (IL-6) levels. In addition, the quality and each study was assessed using either
      the Newcastle Ottawa Scale (NOS) or the Cochrane Risk of Bias tool, and
      reliability of the meta-analytic result using the Grading of Recommendations
      Assessment, Development and Evaluation (GRADE). RESULTS: Of the 839 articles
      initially searched, 11 studies were finally eligible for inclusion. Subgroup
      analysis results showed that comparing with initial value, there was a decline in
      CAS at 1,3,6,12 month after RTX treatment, decreased TRAbs level at 6,12 month,
      proptosis improvement at least 1 month, unchanged IL-6 level at 6 month,
      decreased TSH level at 3 month but unchanged at 12 month. All included studies
      were classified as good quality. CONCLUSIONS: The pooled data suggested that the
      preliminary effects of RTX treatment on TAO might be promising. However, more
      large-sample and high-quality studies targeting RTX use during this disease and
      long-term surveillance of prognosis are urgently needed.

PMID- 29452584
TI  - High phosphorus intake and gut-related parameters - results of a randomized
      placebo-controlled human intervention study.
AB  - BACKGROUND: In recent years, high phosphate intakes were discussed critically. In
      the small intestine, a part of the ingested phosphate and calcium precipitates to
      amorphous calcium phosphate (ACP), which in turn can precipitate other intestinal
      substances, thus leading to a beneficial modulation of the intestinal
      environment. Therefore, we analysed faecal samples obtained from a human
      intervention study regarding gut-related parameters. METHODS: Sixty-two healthy
      subjects (men, n = 30; women, n = 32) completed the double-blind, placebo
      controlled and parallel designed study (mean age: 29 +/- 7 years; mean BMI: 24 +/
      3 kg/m2). Supplements were monosodium phosphate and calcium carbonate. During
      the first 2 weeks, all groups consumed a placebo sherbet powder, and afterwards a
      sherbet powder for 8 weeks according to the intervention group: P1000/Ca0 (1000
      mg/d phosphorus), P1000/Ca500 (1000 mg/d phosphorus and 500 mg/d calcium) and
      P1000/Ca1000 (1000 mg/d phosphorus and 1000 mg/d calcium). After the placebo
      period and after 8 weeks of intervention faecal collections took place. We
      determined in faeces: short-chain fatty acids (SCFA) and fat as well as the
      composition of the microbiome (subgroup) and cyto- and genotoxicity of faecal
      water (FW). By questionnaire evaluation we examined tolerability of the used
      phosphorus supplement. RESULTS: Faecal fat concentrations did not change
      significantly due to the interventions. Concentrations of faecal total SCFA and
      acetate were significantly higher after 8 weeks of P1000/Ca500 supplementation
      compared to the P1000/Ca0 supplementation. In men, faecal total SCFA and acetate
      concentrations were significantly higher after 8 weeks in the P1000/Ca1000 group
      compared to the P1000/Ca0 one. None of the interventions markedly affected cyto-
      and genotoxic activity of FW. Men of the P1000/Ca1000 intervention had a
      significantly different gut microbial community compared to the men of the
      P1000/Ca0 and P1000/Ca500 ones. The genus Clostridium XVIII was significantly
      more abundant in men of the P1000/Ca1000 intervention group compared to the other
      groups. Supplementations did not cause increased intestinal distress.
      CONCLUSIONS: The used high phosphorus diet did not influence cyto- and
      genotoxicity of FW and the concentrations of faecal fat independent of calcium
      intake. Our study provides first hints for a potential phosphorus-induced
      modulation of the gut community and the faecal total SCFA content. TRIAL
      REGISTRATION: The trial is registered at ClinicalTrials.gov as NCT02095392 .

PMID- 29452585
TI  - Beta-2 adrenergic receptors increase TREG cell suppression in an OVA-induced
      allergic asthma mouse model when mice are moderate aerobically exercised.
AB  - BACKGROUND: The potency of T regulatory (TREG) cells to inhibit T helper (Th)
      driven immune cell responses has been linked to increased intracellular cyclic
      AMP (cAMP) levels of TREG cells. In an ovalbumin (OVA)-driven allergic asthma
      mouse model, moderate aerobic exercise increases TREG cell function in a contact
      dependent manner that leads to a significant reduction in chronic inflammation
      and restoration of lung function. However, the mechanism, whereby exercise
      increases TREG function, remains unknown and was the focus of these
      investigations. Exercise can communicate with TREG cells by their expression of
      beta2-adrenergic receptors (beta2-AR). Activation of these receptors results in
      an increase in intracellular levels of cyclic-AMP, potentially creating a potent
      inhibitor of Th cell responses. RESULTS: For the allergic asthma model, female
      wildtype BALB/c mice were challenged with OVA, and exercised (13.5 m/min for 45
      min) 3*/week for 4 weeks. TREG cells were isolated from all mouse asthma/exercise
      groups, including beta2-AR-/- mice, to test suppressive function and
      intracellular cAMP levels. In these studies, cAMP levels were increased in TREG
      cells isolated from exercised mice. When beta2-AR expression was absent on TREG
      cells, cAMP levels were significantly decreased. Correlatively, their suppressive
      function was compromised. Next, TREG cells from all mouse groups were tested for
      suppressive function after treatment with either a pharmaceutical beta2
      adrenergic agonist or an effector-specific cAMP analogue. These experiments
      showed TREG cell function was increased when treated with either a beta2
      adrenergic agonist or effector-specific cAMP analogue. Finally, female wildtype
      BALB/c mice were antibody-depleted of CD25+CD4+ TREG cells (anti-CD25). Twenty
      four hours after TREG depletion, either beta2-AR-/- or wildtype TREG cells were
      adoptively transferred. Recipient mice underwent the asthma/exercise protocols.
      beta2-AR-/- TREG cells isolated from these mice showed no increase in TREG
      function in response to moderate aerobic exercise. CONCLUSION: These studies
      offer a novel role for beta2-AR in regulating cAMP intracellular levels that can
      modify suppressive function in TREG cells.

PMID- 29452586
TI  - The role of glucocorticoid, interleukin-1beta, and antioxidants in prenatal
      stress effects on embryonic microglia.
AB  - Maternal stress during pregnancy is associated with an increased risk of
      psychopathology in offspring. Resident immune cells of the brain, microglia, may
      be mediators of prenatal stress and altered neurodevelopment. Here, we
      demonstrate that neither the exogenous pro-inflammatory cytokine, interleukin
      1beta (IL-1beta), nor the glucocorticoid hormone, corticosterone, recapitulated
      the full effects of prenatal stress on the morphology of microglial cells in the
      cortical plate of embryonic mice; IL-1beta effects showed greater similarity to
      prenatal stress effects on microglia. Unexpectedly, oil vehicle alone, which has
      antioxidant properties, moderated the effects of prenatal stress on microglia.
      Microglia changes with prenatal stress were also sensitive to the antioxidant, N
      acetylcysteine, suggesting redox dysregulation as a mechanism of prenatal stress.

PMID- 29452587
TI  - Timing of abortion among adolescent and young women presenting for post-abortion
      care in Kenya: a cross-sectional analysis of nationally-representative data.
AB  - BACKGROUND: Complications of unsafe abortion are a leading cause of maternal
      mortality in sub-Saharan Africa. Adolescents and young women are
      disproportionately represented among those at risk of these complications.
      Currently, we know little about the factors associated with young women's timing
      of abortion. This study examined the timing of abortion as well as factors
      influencing it among adolescents and young women aged 12-24 years who sought post
      abortion care (PAC) in health facilities in Kenya. METHODS: We draw on data from
      a cross-sectional study on the magnitude and incidence of induced abortion in
      Kenya conducted in 2012. The study surveyed women presenting with a diagnosis of
      incomplete, inevitable, missed, complete, or septic abortion over a one-month
      data collection period in 328 health facilities (levels 2-6). Survey data,
      specifically, from adolescents and young women were analyzed to examine their
      characteristics, the timing of abortion, and the factors associated with the
      timing of abortion. RESULTS: One thousand one hundred forty-five adolescents and
      young women presented for PAC during the data collection period. Eight percent of
      the women reported a previous induced abortion and 78% were not using a modern
      method of contraception about the time of conception. Thirty-nine percent of the
      index abortions occurred after 12 weeks of gestation. A greater proportion of
      women presenting with late abortions (more than 12 weeks gestational age) (46%)
      than those presenting with early abortions (33%) presented with severe
      complications. Controlling for socio-demographic and reproductive history, timing
      of abortion was significantly associated with place of residence (marginal),
      education, parity, clinical stage of abortion and level of severity. CONCLUSIONS:
      Late-term abortions were substantial, and may have contributed substantially to
      the high proportion of women with post-abortion complications. Efforts to reduce
      the severity of abortion-related morbidities and mortality must target young
      women, particularly those living in rural and other remote areas. Interventions
      to reduce unintended pregnancies in this population are also urgently needed to
      improve early pregnancy detection and timely care seeking.

PMID- 29452588
TI  - Correction to: The antiangiogenic activities of ethanolic crude extracts of four
      Salvia species.
AB  - CORRECTION: After the publication [1] it came to the attention of the authors
      that one of the co-authors was incorrectly included as Hamza Somrain. The correct
      spelling is as follows: Hamzeh Sumrein.

PMID- 29452589
TI  - Does additional support provided through e-mail or SMS in a Web-based Social
      Marketing program improve children's food consumption? A Randomized Controlled
      Trial.
AB  - BACKGROUND: The FAN Social Marketing program was developed to improve dietary and
      physical activity habits of families with children in Ticino, Switzerland. The
      aim of this study was to examine if the effects of the program on children's food
      intake differed by intervention group. METHODS: Effects of the FAN program were
      tested through a Randomized Controlled Trial. The program lasted 8 weeks, during
      which participants received tailored communication about nutrition and physical
      activity. Families were randomly allocated to one of three groups, where the
      parent received the intervention by the Web (G1), Web + e-mail (G2) or Web + SMS
      (G3). Children in all groups received tailored print letters by post. Children's
      food consumption was assessed at baseline and immediate post intervention using a
      7-day food diary. Generalized linear mixed models with child as a random effect
      and with time, treatment group, and the time by treatment interaction as fixed
      effects were used to test the impact of the intervention. RESULTS: Analyses were
      conducted with a sample of 608 children. After participating in FAN the marginal
      means of daily consumption of fruit changed from 0.95 to 1.12 in G1, from 0.82 to
      0.94 in G2, and from 0.93 to 1.18 in G3. The margins of the daily consumption of
      sweets decreased in each group (1.67 to 1.56 in G1, 1.71 to 1.49 in G2, and 1.72
      to 1.62 in G3). The change in vegetable consumption observed from pre to post
      intervention in G3 (from 1.13 to 1.21) was significantly different from that
      observed in G1 (from 1.21 to 1.17). CONCLUSIONS: A well-designed Web-based Social
      Marketing intervention complemented with print letters can help improve
      children's consumption of water, fruit, soft drinks, and sweets. The use of SMS
      to support greater behavior change, in addition to Web-based communication,
      resulted only in a small significant positive change for vegetables, while the
      use of e-mail in addition to Web did not result in any significant difference.
      TRIAL REGISTRATION: The trial was retrospectively registered in the ISRCTN
      registry (ID ISRCTN48730279 ).

PMID- 29452590
TI  - Factors associated with persistent posttraumatic stress disorder among U.S.
      military service members and veterans.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) can have long-term and far
      reaching impacts on health and social and occupational functioning. This study
      examined factors associated with persistent PTSD among U.S. service members and
      veterans. METHODS: Using baseline and follow-up (2001-2013) questionnaire data
      collected approximately every 3 years from the Millennium Cohort Study,
      multivariable logistic regression was conducted to determine factors associated
      with persistent PTSD. Participants included those who screened positive for PTSD
      using the PTSD Checklist-Civilian Version at baseline (N = 2409). Participants
      were classified as having remitted or persistent PTSD based on screening negative
      or positive, respectively, at follow-up. RESULTS: Almost half of participants (N
      = 1132; 47%) met criteria for persistent PTSD at the first follow-up; of those,
      804 (71%) also screened positive for PTSD at the second follow-up. Multiple
      factors were independently associated with persistent PTSD in an adjusted model
      at the first follow-up, including older age, deployment with high combat
      exposure, enlisted rank, initial PTSD severity, depression, history of physical
      assault, disabling injury/illness, and somatic symptoms. Among those with
      persistent PTSD at the first follow-up, additional factors of less sleep,
      separation from the military, and lack of social support were associated with
      persistent PTSD at the second follow-up. CONCLUSIONS: Combat experiences and PTSD
      severity were the most salient risk factors for persistent PTSD. Comorbid
      conditions, including injury/illness, somatic symptoms, and sleep problems, also
      played a significant role and should be addressed during treatment. The high
      percentage of participants with persistent PTSD supports the need for more
      comprehensive and accessible treatment, especially after separation from the
      military.

PMID- 29452591
TI  - Ageing-associated DNA methylation dynamics are a molecular readout of lifespan
      variation among mammalian species.
AB  - BACKGROUND: Mammalian species exhibit a wide range of lifespans. To date, a
      robust and dynamic molecular readout of these lifespan differences has not yet
      been identified. Recent studies have established the existence of ageing
      associated differentially methylated positions (aDMPs) in human and mouse. These
      are CpG sites at which DNA methylation dynamics show significant correlations
      with age. We hypothesise that aDMPs are pan-mammalian and are a dynamic molecular
      readout of lifespan variation among different mammalian species. RESULTS: A large
      scale integrated analysis of aDMPs in six different mammals reveals a strong
      negative relationship between rate of change of methylation levels at aDMPs and
      lifespan. This relationship also holds when comparing two different dog breeds
      with known differences in lifespans. In an ageing cohort of aneuploid mice
      carrying a complete copy of human chromosome 21, aDMPs accumulate far more
      rapidly than is seen in human tissues, revealing that DNA methylation at aDMP
      sites is largely shaped by the nuclear trans-environment and represents a robust
      molecular readout of the ageing cellular milieu. CONCLUSIONS: Overall, we define
      the first dynamic molecular readout of lifespan differences among mammalian
      species and propose that aDMPs will be an invaluable molecular tool for future
      evolutionary and mechanistic studies aimed at understanding the biological
      factors that determine lifespan in mammals.

PMID- 29452592
TI  - Considering mean and inequality health outcomes together: the population health
      performance index.
AB  - BACKGROUND: The purpose was to develop and test a population health measure that
      combines mean health outcomes and inequalities into a single GDP-like metric to
      help policymakers measure population health performance on both dimensions in one
      metric. METHODS: The Population Health Performance Index is a weighted average of
      a mean index and an inequality index according to the user's inequality aversion.
      We deploy this methodology for two combinations of health outcome and disparity
      domain: infant mortality by race and unhealthy days by education. RESULTS: The
      PHPI is bounded between 0 and 1, and is comprised of a weighted average of two
      separate indices: a mean index and an inequality index, with 1 representing the
      ideal state of no ill health and no inequality and 0 representing the worst state
      in the U.S. PHPI values across states (neutral 50:50 weighting) vary between 0.60
      (Massachusetts) to 0.17 (Delaware) for infant mortality by race and between 0.65
      (North Dakota) to 0.00 (West Virginia) for unhealthy days by education. For some
      states, the choice of inequality aversion significantly impacts their PHPI value
      and state rank. CONCLUSIONS: Mean and inequality health outcomes can be combined
      into a single Population Health Performance Index for use by public and private
      policy makers, like the GDP is used as a summary metric to measure economic
      output. The index can allow for varying degrees of inequality aversion, an
      individual's or jurisdiction's value choice that can substantially impact the
      value of this new summary population health metric.

PMID- 29452594
TI  - Comparative immunogenicity of preparations of yeast-derived dengue oral vaccine
      candidate.
AB  - BACKGROUND: Dengue is listed as a neglected tropical disease by the Center for
      Disease Control and Preservation, as there are insufficient integrated
      surveillance strategies, no effective treatment, and limited licensed vaccines.
      Consisting of four genetically distinct serotypes, dengue virus (DENV) causes
      serious life-threatening infections due to its complexity. Antibody-dependent
      enhancement by pre-existing cross-reactive as well as homotypic antibodies
      further worsens the clinical symptoms of dengue. Thus, a vaccine conferring
      simultaneous and durable immunity to each of the four DENV serotypes is essential
      to restrict its escalation. In deeply affected resource-limited countries, oral
      vaccination using food-grade organisms is considered to be a beneficial approach
      in terms of costs, patient comfort, and simple logistics for mass immunization.
      The current study used a mouse model to explore the immunogenicity of an oral
      dengue vaccine candidate prepared using whole recombinant yeast cells (WC) and
      cell-free extracts (CFE) from cells expressing recombinant Escherichia coli heat
      labile toxin protein B-subunit (LTB) fused to the consensus dengue envelope
      domain III (scEDIII). Mice were treated orally with recombinant WC and CFE
      vaccines in 2-week intervals for 4 weeks and changes in systemic and mucosal
      immune responses were monitored. RESULTS: Both WC and CFE dosage applications of
      LTB-scEDIII stimulated a systemic humoral immune response in the form of dengue
      specific serum IgG as well as mucosal immune response in the form of secretory
      sIgA. Antigen-specific B cell responses in isolated lymphoid cells from the
      spleen and Peyer's patches further indicated an elevated mucosal immune response.
      Cellular immune response estimated through lymphocyte proliferation assay
      indicated higher levels in CFE than WC dosage. Furthermore, sera obtained after
      both oral administrations successfully neutralized DENV-1, whereas CFE
      formulation only neutralized DENV-2 serotype, two representative serotypes which
      cause severe dengue infection. Sera from mice that were fed CFE preparations
      demonstrated markedly higher neutralizing titers compared to those from WC-fed
      mice. However, WC feeding elicited strong immune responses, which were similar to
      the levels induced by CFE feeding after intraperitoneal booster with purified
      scEDIII antigen. CONCLUSIONS: CFE preparations of LTB-scEDIII produced strong
      immunogenicity with low processing requirements, signifying that this fusion
      protein shows promise as a potent oral vaccine candidate against dengue viral
      infection.

PMID- 29452595
TI  - Fertility preservation healthcare circuit and networks in cancer patients
      worldwide: what are the issues?
AB  - BACKGROUND: Fertility preservation (FP) is a major determinant of quality of life
      after cancer remission for women who may not have achieved their ideal family
      size. This article describes the FP services and strategy currently available,
      highlighting issues of oncofertility worldwide. For these patients in complex
      situations, health networks are essential to improve coordination of care, and
      the strengthening of this coordination is a major challenge to improve the
      performance of the health system. Two international networks have been created in
      order to foster scientific exchange between countries and to standardize the
      oncofertility healthcare circuit. However, the paucity of referral nationwide
      networks lead to a structural gap in health care policies. SHORT CONCLUSION:
      Management strategies of oncofertility in the world are still fragile and uneven.
      To structure the oncofertility sector, a multidisciplinary project allowing teams
      to collaborate is of utmost importance particularly in low and middle-income
      countries.

PMID- 29452593
TI  - A review on biosynthesis of silver nanoparticles and their biocidal properties.
AB  - Use of silver and silver salts is as old as human civilization but the
      fabrication of silver nanoparticles (Ag NPs) has only recently been recognized.
      They have been specifically used in agriculture and medicine as antibacterial,
      antifungal and antioxidants. It has been demonstrated that Ag NPs arrest the
      growth and multiplication of many bacteria such as Bacillus cereus,
      Staphylococcus aureus, Citrobacter koseri, Salmonella typhii, Pseudomonas
      aeruginosa, Escherichia coli, Klebsiella pneumonia, Vibrio parahaemolyticus and
      fungus Candida albicans by binding Ag/Ag+ with the biomolecules present in the
      microbial cells. It has been suggested that Ag NPs produce reactive oxygen
      species and free radicals which cause apoptosis leading to cell death preventing
      their replication. Since Ag NPs are smaller than the microorganisms, they diffuse
      into cell and rupture the cell wall which has been shown from SEM and TEM images
      of the suspension containing nanoparticles and pathogens. It has also been shown
      that smaller nanoparticles are more toxic than the bigger ones. Ag NPs are also
      used in packaging to prevent damage of food products by pathogens. The toxicity
      of Ag NPs is dependent on the size, concentration, pH of the medium and exposure
      time to pathogens.

PMID- 29452596
TI  - Relationship between polyunsaturated fatty acid composition in serum
      phospholipids, systemic low-grade inflammation, and glycemic control in patients
      with type 2 diabetes and atherosclerotic cardiovascular disease.
AB  - BACKGROUND: There are inconsistent data about the role of serum phospholipid
      fatty acid composition in patients with type 2 diabetes (T2DM) and
      atherosclerotic cardiovascular disease (ASCVD). The aim of the study was to
      investigate the relationship between serum phospholipid fatty acid composition,
      systemic low-grade inflammation, and glycemic control in high-risk T2DM patients.
      METHODS: Seventy-four patients (26% women, mean age 65.6 +/- 6.8 years) with T2DM
      (median diabetes duration 10 years) and documented ASCVD (74 with coronary artery
      disease, 26 with peripheral arterial disease) were enrolled in the study.
      Baseline HbA1c was estimated using turbidimetric inhibition immunoassay.
      According to the median value of HbA1c the patients were grouped into those with
      HbA1c < 7.0% (< 53 mmol/mol) (n = 38) and those with HbA1c >= 7.0% (>= 53
      mmol/mol) (n = 36). Serum phospholipid fatty acids were measured with gas
      chromatography. RESULTS: Patients with HbA1c >= 7.0%, compared with those with
      HbA1c < 7.0% had similar composition of saturated and monounsaturated fatty acids
      in serum phospholipids, but had higher concentrations of linoleic acid (LA) and
      higher n-6/n-3 polyunsaturated fatty acid (PUFA) ratio as well as lower levels of
      eicosapentaenoic acid (EPA), total n-3 PUFAs, and the EPA/arachidonic acid ratio.
      We found that LA (r = 0.25; p = 0.03) and n-6/n-3 PUFA ratio (r = 0.28; p = 0.02)
      were positively correlated with HbA1c. Multivariate logistic regression analysis
      showed that n-6/n-3 PUFA ratio, hsCRP and T2DM duration were independent
      predictors of worse glycemic control in patients with T2DM and ASCVD.
      CONCLUSIONS: This study showed that glycemic control in high-risk T2DM patients
      with ASCVD was significantly associated with unfavorable serum phospholipid n-6/n
      3 PUFA ratio and greater systemic inflammation.

PMID- 29452597
TI  - Evidence of reduced treatment adherence among HIV infected paediatric and
      adolescent populations in Nairobi at the onset of the UNAIDS Universal Test and
      Treat Program.
AB  - OBJECTIVE: We conducted a retrospective cohort study to evaluate the efficacy of
      the World Health Organization (WHO) "Universal Test and Treat" (UTT) policy,
      initiated in Kenya in September 2016. Under this policy, every human
      immunodeficiency virus (HIV)-infected person should be initiated on
      antiretroviral therapy (ART). We compared intra- and inter-group viral
      suppression and ART adherence rates for pre-UTT (initiated on ART in March-August
      2016) and UTT groups (initiated in September 2016). The study was conducted in a
      community outreach Program in Nairobi with 3500 HIV-infected children enrolled.
      RESULTS: 122 children and adolescents were initiated on first-line ART pre-UTT,
      and 197 during the UTT period. The 6 month viral suppression rate was 79.7% pre
      UTT versus 76.6% UTT (P < 0.05). Suboptimal adherence was higher in the UTT than
      pre-UTT period (88 of 197, 44.7% and 44 of 122, 34%; P < 0.001). The decrease in
      adherence was greater among orphans (91.7% pre-UTT and 87.2% UTT, P = 0.001) and
      children 11-18 years. Our results show that successful implementation of the UTT
      policy in Africa is challenged by an increased risk of suboptimal adherence.
      There is a need to develop extra strategies to support adherence, especially
      among orphans and teenagers.

PMID- 29452598
TI  - 7 versus 14 days of antibiotic treatment for critically ill patients with
      bloodstream infection: a pilot randomized clinical trial.
AB  - BACKGROUND: Shorter-duration antibiotic treatment is sufficient for a range of
      bacterial infections, but has not been adequately studied for bloodstream
      infections. Our systematic review, survey, and observational study indicated
      equipoise for a trial of 7 versus 14 days of antibiotic treatment for bloodstream
      infections; a pilot randomized clinical trial (RCT) was a necessary next step to
      assess feasibility of a larger trial. METHODS: We conducted an open, pilot RCT of
      antibiotic treatment duration among critically ill patients with bloodstream
      infection across 11 intensive care units (ICUs). Antibiotic selection, dosing and
      route were at the discretion of the treating team; patients were randomized 1:1
      to intervention arms consisting of two fixed durations of treatment - 7 versus 14
      days. We recruited adults with a positive blood culture yielding pathogenic
      bacteria identified while in ICU. We excluded patients with severe
      immunosuppression, foci of infection with an established requirement for
      prolonged treatment, single cultures with potential contaminants, or cultures
      yielding Staphylococcus aureus or fungi. The primary feasibility outcomes were
      recruitment rate and adherence to treatment duration protocol. Secondary outcomes
      included 90-day, ICU and hospital mortality, relapse of bacteremia, lengths of
      stay, mechanical ventilation and vasopressor duration, antibiotic-free days,
      Clostridium difficile, antibiotic adverse events, and secondary infection with
      antimicrobial-resistant organisms. RESULTS: We successfully achieved our target
      sample size (n = 115) and average recruitment rate of 1 (interquartile range
      (IQR) 0.3-1.5) patient/ICU/month. Adherence to treatment duration was achieved in
      89/115 (77%) patients. Adherence differed by underlying source of infection:
      26/31 (84%) lung; 18/29 (62%) intra-abdominal; 20/26 (77%) urinary tract; 8/9
      (89%) vascular-catheter; 4/4 (100%) skin/soft tissue; 2/4 (50%) other; and 11/12
      (92%) unknown sources. Patients experienced a median (IQR) 14 (8-17) antibiotic
      free days (of the 28 days after blood culture collection). Antimicrobial-related
      adverse events included hepatitis in 1 (1%) patient, Clostridium difficile
      infection in 4 (4%), and secondary infection with highly resistant microorganisms
      in 10 (9%). Ascertainment was complete for all study outcomes in ICU, in hospital
      and at 90 days. CONCLUSION: It is feasible to conduct a RCT to determine whether
      7 versus 14 days of antibiotic treatment is associated with comparable 90-day
      survival. TRIAL REGISTRATION: ClinicalTrials.gov , identifier: NCT02261506 .
      Registered on 26 September 2014.

PMID- 29452599
TI  - Feasibility and acceptability of PrE-operative Physical Activity to improve
      patient outcomes After major cancer surgery: study protocol for a pilot
      randomised controlled trial (PEPA Trial).
AB  - BACKGROUND: There is a need for evidence of the effectiveness of pre-operative
      exercise for patients undergoing major cancer surgery; however, recruitment to
      such trials can be challenging. The PrE-operative Physical Activity (PEPA) Trial
      will establish the feasibility and acceptability of a pre-operative exercise
      programme aimed to improve patient outcomes after cytoreductive surgery and
      pelvic exenteration. The secondary aim is to obtain pilot data on the likely
      difference in key outcomes (post-operative complications, length of hospital
      stay, post-operative functional capacity and quality of life) to inform the
      sample size calculation for the substantive randomised clinical trial.
      METHODS/DESIGN: Twenty patients undergoing cytoreductive surgery and pelvic
      exenteration at the Royal Prince Alfred Hospital, Sydney will be recruited and
      randomly allocated (1:1 ratio) to either 2 to 6 weeks' pre-operative exercise
      programme (intervention group) or usual care (control group). Those randomised to
      the intervention group will receive up to six individualised, 1-h physiotherapy
      sessions (including aerobic and endurance exercises, respiratory muscle
      exercises, stretching and flexibility exercises), home exercises (instruction and
      recommendations on how to progress the exercises at home) and encouragement to be
      more active by using an activity tracker to measure the number of steps walked
      daily. Patients allocated to the control group will not receive any specific
      advice about exercise training. Feasibility will be assessed with consent rates
      to the study, and for the intervention group, retention and adherence rates to
      the exercise programme. Acceptability of the exercise programme will be assessed
      with a semi-structured questionnaire. The following measures of the effectiveness
      of the intervention will be collected at baseline (2 to 6 weeks pre-operative), a
      week before surgery, during hospital stay and pre hospital discharge: post
      operative complication rates (Clavien-Dindo), post-operative functional capacity
      (Six-minute Walk Test) and quality of life (SF-36v2(r)) and length of hospital
      stay. Functional status will be additionally measured using Cardiopulmonary
      Exercise Testing (CPET), at baseline and within a week before surgery.
      DISCUSSION: The PEPA Trial will provide important information about the
      feasibility and acceptability of a pre-operative exercise programme for patients
      undergoing major cancer surgery. Data from the PEPA Trial will be used to inform
      the design, methodology and to calculate sample size required for a larger,
      definitive trial. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry, ID: ACTRN12617001129370 . Registered on 1 August 2017.

PMID- 29452600
TI  - Patterns of paediatric end-of-life care: a chart review across different care
      settings in Switzerland.
AB  - BACKGROUND: Paediatric end-of-life care is challenging and requires a high level
      of professional expertise. It is important that healthcare teams have a thorough
      understanding of paediatric subspecialties and related knowledge of disease
      specific aspects of paediatric end-of-life care. The aim of this study was to
      comprehensively describe, explore and compare current practices in paediatric end
      of-life care in four distinct diagnostic groups across healthcare settings
      including all relevant levels of healthcare providers in Switzerland. METHODS: In
      this nationwide retrospective chart review study, data from paediatric patients
      who died in the years 2011 or 2012 due to a cardiac, neurological or oncological
      condition, or during the neonatal period were collected in 13 hospitals, two long
      term institutions and 10 community-based healthcare service providers throughout
      Switzerland. RESULTS: Ninety-three (62%) of the 149 reviewed patients died in
      intensive care units, 78 (84%) of them following withdrawal of life-sustaining
      treatment. Reliance on invasive medical interventions was prevalent, and the use
      of medication was high, with a median count of 12 different drugs during the last
      week of life. Patients experienced an average number of 6.42 symptoms. The
      prevalence of various types of symptoms differed significantly among the four
      diagnostic groups. Overall, our study patients stayed in the hospital for a
      median of six days during their last four weeks of life. Seventy-two patients
      (48%) stayed at home for at least one day and only half of those received
      community-based healthcare. CONCLUSIONS: The study provides a wide-ranging
      overview of current end-of-life care practices in a real-life setting of
      different healthcare providers. The inclusion of patients with all major
      diagnoses leading to disease- and prematurity-related childhood deaths, as well
      as comparisons across the diagnostic groups, provides additional insight and
      understanding for healthcare professionals. The provision of specialised
      palliative and end-of-life care services in Switzerland, including the capacity
      of community healthcare services, need to be expanded to meet the specific needs
      of seriously ill children and their families.

PMID- 29452602
TI  - The quest for a framework for sustainable and institutionalised priority-setting
      for health research in a low-resource setting: the case of Zambia.
AB  - BACKGROUND: Priority-setting for health research in low-income countries remains
      a major challenge. While there have been efforts to systematise and improve the
      processes, most of the initiatives have ended up being a one-off exercise and are
      yet to be institutionalised. This could, in part, be attributed to the limited
      capacity for the priority-setting institutions to identify and fund their own
      research priorities, since most of the priority-setting initiatives are driven by
      experts. This paper reports findings from a pilot project whose aim was to
      develop a systematic process to identify components of a locally desirable and
      feasible health research priority-setting approach and to contribute to capacity
      strengthening for the Zambia National Health Research Authority. METHODS:
      Synthesis of the current literature on the approaches to health research
      prioritisations. The results of the synthesis were presented and discussed with a
      sample of Zambian researchers and decision-makers who are involved in health
      research priority-setting. The ultimate aim was for them to explore the different
      approaches available for guiding health research priority-setting and to identify
      an approach that would be relevant and feasible to implement and sustain within
      the Zambian context. RESULTS: Based on the evidence that was presented, the
      participants were unable to identify one approach that met the criteria. They
      identified attributes from the different approaches that they thought would be
      most appropriate and proposed a process that they deemed feasible within the
      Zambian context. CONCLUSION: While it is easier to implement prioritisation based
      on one approach that the initiator might be interested in, researchers interested
      in capacity-building for health research priority-setting organisations should
      expose the low-income country participants to all approaches. Researchers ought
      to be aware that sometimes one shoe may not fit all, as in the case of Zambia,
      instead of choosing one approach, the stakeholders may select desirable
      attributes from the different approaches and piece together an approach that
      would be feasible and acceptable within their context. An approach that builds on
      the decision-makers' understanding of their contexts and their input to its
      development would foster local ownership and has a greater potential for
      sustainability.

PMID- 29452601
TI  - Reactive hyperemia index (RHI) and cognitive performance indexes are associated
      with histologic markers of liver disease in subjects with non-alcoholic fatty
      liver disease (NAFLD): a case control study.
AB  - BACKGROUND: No study evaluated vascular health markers in subjects with non
      alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive
      hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes.
      AIM OF THE STUDY: We aimed to assess whether NAFLD and its histological severity
      are associated with impairment of arterial stiffness and RH-PAT indexes in a
      mixed cohort of patients with biopsy-proven NAFLD. MATERIALS AND METHODS: The
      Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV)
      and augmentation index (Aix) were used as markers of arterial stiffness, whereas
      endothelial function was assessed using reactive hyperemia index (RHI). The mini
      mental state examination (MMSE) was administered to test cognitive performance.
      RESULTS: 80 consecutive patients with biopsy-proven NAFLD and 83 controls without
      fatty liver disease. NAFLD subjects showed significantly lower mean RHI, higher
      mean arterial stiffness indexes and lower mean MMSE score. Multivariable analysis
      after correction for BMI, dyslipidaemia, hypertension, sex, diabetes, age and
      cardiovascular disease showed that BMI, diastolic blood pressure and RHI are
      significantly associated to NAFLD. Simple linear regression analysis showed among
      non-alcoholic steatohepatitis (NASH) subjects a significant negative relationship
      between ballooning grade and MMSE and a significant positive association between
      Kleiner steatosis grade and augmentation index. CONCLUSIONS: Future research will
      be addressed to evaluate the relationship between inflammatory markers and
      arterial stiffness and endothelial function indexes in NAFLD subjects. These
      study will evaluate association between cardiovascular event incidence and
      arterial stiffness, endothelial and cognitive markers, and they will address the
      beneficial effects of cardiovascular drugs such as statins and ACE inhibitors on
      these surrogate markers in NAFLD subjects.

PMID- 29452603
TI  - The effects of Desflurane and Sevoflurane on Nesfatin-1 levels in laparoscopic
      Cholecystectomy: a randomized controlled trial.
AB  - BACKGROUND: Nesfatin-1 is involved in cardiovascular regulation, stress-related
      responses. The objective of this study is to investigate the impact of volatile
      anesthetics on Nesfatin-1 levels. METHOD: Fourty-two patients aged 30-65 years
      with the American Society Anesthesiology (ASA) Class I-II who were scheduled for
      laparoscopic cholecystectomy were included in the study Patients were randomized
      into two group; desflurane administered group (Group I, n = 21) and sevoflurane
      administered group (Group II, n = 21). For anesthesia maintenance, the patients
      received 6% desflurane or 2% sevoflurane in 40% O2 and 60% air. The patient's
      heart rate (HR), mean, systolic and diastolic arterial pressures (MAP, SAP, DAP),
      peripheral O2 saturation (SpO2) were monitored and recorded before induction,
      after induction, after intubation, and during extubation. Blood samples were
      collected before induction (T1), and after extubation when aldrete score was 10
      (T2). RESULTS: Demographic data were similar between the groups. The preoperative
      levels of nesfatin were similar in the two groups (p = 0.715). In desflurane
      group, post-operative nesfatin levels were similar compared to preoperative
      levels (p = 0.073). In sevoflurane group, post-operative nesfatin levels were
      similar (p = 0.131). The nesfatin levels (postoperative vs preoperative) were
      similar between the groups (p = 0.900). CONCLUSION: In conclusion, this study
      results suggest that nesfatin-1 levels are not affected by the use of sevoflurane
      or desflurane in patients undergoing laparoscopic cholecystectomy. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry,
      ACTRN12617001023347 , retrospectively registered on 17 July 2017.

PMID- 29452604
TI  - Transcriptional regulation of ependymal cell maturation within the postnatal
      brain.
AB  - BACKGROUND: Radial glial stem cells within the developing nervous system generate
      a variety of post-mitotic cells, including neurons and glial cells, as well as
      the specialised multi-ciliated cells that line the walls of the ventricular
      system, the ependymal cells. Ependymal cells separate the brain parenchyma from
      the cerebrospinal fluid and mediate osmotic regulation, the flow of cerebrospinal
      fluid, and the subsequent dispersion of signalling molecules via the co-ordinated
      beating of their cilia. Deficits to ependymal cell development and function have
      been implicated in the formation of hydrocephalus, but the transcriptional
      mechanisms underpinning ependymal development remain poorly characterised.
      FINDINGS: Here, we demonstrate that the transcription factor nuclear factor IX
      (NFIX) plays a central role in the development of the ependymal cell layer of the
      lateral ventricles. Expression of ependymal cell-specific markers is delayed in
      the absence of Nfix. Moreover, Nfix-deficient mice exhibit aberrant ependymal
      cell morphology at postnatal day 15, culminating in abnormal thickening and
      intermittent loss of this cell layer. Finally, we reveal Foxj1, a key factor
      promoting ependymal cell maturation, as a target for NFIX-mediated
      transcriptional activation. CONCLUSIONS: Collectively, our data indicate that
      ependymal cell development is reliant, at least in part, on NFIX expression,
      further implicating this transcription factor as a mediator of multiple aspects
      of radial glial biology during corticogenesis.

PMID- 29452605
TI  - Extraordinary disease-free survival in a rare malignant extrarenal rhabdoid
      tumor: a case report and review of the literature.
AB  - BACKGROUND: Malignant extrarenal rhabdoid tumor of the gastrointestinal tract is
      rarely reported in the literature. It is characterized by poor prognosis and
      aggressive metastatic features. A literature review evidenced only 19 cases, with
      poor outcome. CASE PRESENTATION: We report a case of a colonic "pure" malignant
      extrarenal rhabdoid tumor with metastatic nodes in a 65-year-old Caucasian man.
      He was treated surgically with no recurrence, no adjuvant chemotherapy, and with
      4-year survival without disease at the time of the submission of this article.
      CONCLUSIONS: We present an extraordinary case of long-term survival due to the
      extended surgical treatment. We believe that the absence of organ metastasis at
      presentation is a positive prognostic factor, although pathology confirmed node
      involvement (13/38 positive) on microscopy.

PMID- 29452606
TI  - Correction to: Integrating multiple data sources (MUDS) for meta-analysis to
      improve patient-centered outcomes research: a protocol for a systematic review.
AB  - CORRECTION: The correct title of the article [1] should be "Integrating multiple
      data sources (MUDS) for meta-analysis to improve patient-centered outcomes
      research: a protocol". The article is a protocol for a methodological study, not
      a systematic review.

PMID- 29452607
TI  - A Master Switch in Thiopeptide Biosynthesis.
AB  - Although considerable knowledge of the biosynthetic machinery of thiopeptide
      antibiotics has been accumulated, the regulation of their production remains
      unclear. In this issue of Cell Chemical Biology, Li et al. (2018) have now
      characterized a key transcription factor and suggest its feedback regulation by
      biosynthesis intermediates and the final product.

PMID- 29452608
TI  - Insights into an Ancient Atypical Kinase Essential for Biosynthesis of Coenzyme
      Q.
AB  - COQ8 proteins are homologs of atypical protein kinases required for the
      biosynthesis of coenzyme Q (CoQ). In this issue of Cell Chemical Biology,
      Reidenbach et al. (2018) show that COQ8 has an ATPase activity, required for CoQ
      biosynthesis, that is strongly activated by cardiolipin and small molecule mimics
      of early CoQ intermediates.

PMID- 29452609
TI  - Screening Drugs for Kidney Disease: Targeting the Podocyte.
AB  - Podocytes cover the kidney glomerular basement membrane and present the final
      barrier in the renal filtration system. Podocyte loss, observed in most kidney
      diseases, correlates with kidney function decline. In this issue of Cell Chemical
      Biology, Seiber et al. (2018), using a high-throughput chemical screen,
      identified the compound CDG-0876, which improved podocyte survival.

PMID- 29452610
TI  - The plasma membrane calcium pumps-The old and the new.
AB  - The plasma membrane Ca2+-ATPase (PMCA) pumps play a critical role in the
      maintenance of calcium (Ca2+) homeostasis, crucial for optimal neuronal function
      and cell survival. Loss of Ca2+ homeostasis is a key precursor in neuronal
      dysfunction associated with brain aging and in the pathogenesis of
      neurodegenerative disorders. In this article, we review evidence showing age
      related changes in the PMCAs in synaptic plasma membranes (SPMs) and lipid raft
      microdomains isolated from rat brain. Both PMCA activity and protein levels
      decline progressively with increasing age. However, the loss of activity is
      disproportionate to the reduction of protein levels suggesting the presence of
      dysfunctional PMCA molecules in aged brain. PMCA activity is also diminished in
      post-mortem human brain samples from Alzheimer's disease and Parkinson's disease
      patients and in cell models of these neurodegenerative disorders. Experimental
      reduction of the PMCAs not only alter Ca2+ homeostasis but also have diverse
      effects on neurons such as reduced neuritic network, impaired release of
      neurotransmitter and increased susceptibility to stressful stimuli, particularly
      to agents that elevate intracellular Ca2+ [Ca2+]i. Loss of PMCA is likely to
      contribute to neuronal dysfunction observed in the aging brain and in the
      development of age-dependent neurodegenerative disorders. Therapeutic
      (pharmacological and/or non-pharmacological) approaches that can enhance PMCA
      activity and stabilize [Ca2+]i homeostasis may be capable of preventing, slowing,
      and/or reversing neuronal degeneration.

PMID- 29452611
TI  - PMCA2 pump mutations and hereditary deafness.
AB  - Hair cells of the inner ear detect sound stimuli, inertial or gravitational
      forces by deflection of their apical stereocilia. A small number of stereociliary
      cation-selective mechanotransduction (MET) channels admit K+ and Ca2+ ions into
      the cytoplasm promoting hair cell membrane depolarization and, consequently,
      neurotransmitter release at the cell basolateral pole. Ca2+ influx into the
      stereocilia compartment is counteracted by the unusual w/a splicing variant of
      plasma-membrane calcium-pump isoform 2 (PMCA2) which, unlike other PMCA2
      variants, increases only marginally its activity in response to a rapid variation
      of the cytoplasmic free Ca2+ concentration ([Ca2+]c). Missense mutations of
      PMCA2w/a cause deafness and loss of balance in humans. Mouse models in which the
      pump is genetically ablated or mutated show hearing and balance impairment, which
      correlates with defects in homeostatic regulation of stereociliary [Ca2+]c,
      decreased sensitivity of mechanotransduction channels to hair bundle displacement
      and progressive degeneration of the organ of Corti. These results highlight a
      critical role played by the PMCA2w/a pump in the control of hair cell function
      and survival, and provide mechanistic insight into the etiology of deafness and
      vestibular disorders.

PMID- 29452612
TI  - Survival strategies for mouse cerebellar Purkinje neurons lacking PMCA2.
AB  - Expression of the fast calcium extrusion protein, PMCA2, in the cerebellum is
      amongst the highest found throughout the central nervous system, and
      unsurprisingly PMCA2 knockout mice exhibit cerebellar ataxia or loss of
      controlled movement. The sole output neurons of the cerebellar cortex, Purkinje
      neurons, are functionally compromised in these knockout mice, yet remarkably
      these neurons survive. In this mini-review we review and speculate on the
      importance of multiple PMCA2 dependent actions at cellular and synaptic sites
      within the cerebellar Purkinje neuron network. We also explore how loss of PMCA2
      /- can lead to the ataxic phenotype, but can paradoxically also minimise calcium
      rises in cerebellar Purkinje neurons, thereby ensuring their resilience and
      survival.

PMID- 29452613
TI  - The role of Plasma Membrane Calcium ATPases (PMCAs) in neurodegenerative
      disorders.
AB  - Selective degeneration of differentiated neurons in the brain is the unifying
      feature of neurodegenerative disorders such as Parkinson's disease (PD) or
      Alzheimer's disease (AD). A broad spectrum of evidence indicates that initially
      subtle, but temporally early calcium dysregulation may be central to the
      selective neuronal vulnerability observed in these slowly progressing, chronic
      disorders. Moreover, it has long been evident that excitotoxicity and its major
      toxic effector mechanism, neuronal calcium overload, play a decisive role in the
      propagation of secondary neuronal death after acute brain injury from trauma or
      ischemia. Under physiological conditions, neuronal calcium homeostasis is
      maintained by a fine-tuned interplay between calcium influx and releasing
      mechanisms (Ca2+-channels), and calcium efflux mechanisms (Ca2+-pumps and 
      exchangers). Central functional components of the calcium efflux machinery are
      the Plasma Membrane Calcium ATPases (PMCAs), which represent high-affinity
      calcium pumps responsible for the ATP-dependent removal of calcium out of the
      cytosol. Beyond a growing body of experimental evidence, it is their high
      expression level, their independence of secondary ions or membrane potential,
      their profound redox regulation and autoregulation, their postsynaptic
      localization in close proximity to the primary mediators of pathological calcium
      influx, i.e. NMDA receptors, as well as evolutionary considerations which all
      suggest a pivotal role of the PMCAs in the etiology of neurodegeneration and make
      them equally challenging and alluring candidates for drug development. This
      review aims to summarize the recent literature on the role of PMCAs in the
      pathogenesis of neurodegenerative disorders.

PMID- 29452614
TI  - The presynaptic active zone: molecules, plasticity, and diseases.

PMID- 29452615
TI  - Fever of Unknown Origin: the Value of FDG-PET/CT.
AB  - Fever of unknown origin (FUO) is commonly defined as fever higher than 38.3
      degrees C on several occasions during at least 3 weeks with uncertain diagnosis
      after a number of obligatory investigations. The differential diagnosis of FUO
      can be subdivided in four categories: infections, malignancies, noninfectious
      inflammatory diseases, and miscellaneous causes. In most cases of FUO, there is
      an uncommon presentation of a common disease. FDG-PET/CT is a sensitive
      diagnostic technique for the evaluation of FUO by facilitating anatomical
      localization of focally increased FDG uptake, thereby guiding further diagnostic
      tests to achieve a final diagnosis. FDG-PET/CT should become a routine procedure
      in the workup of FUO when diagnostic clues are absent. FDG-PET/CT appears to be a
      cost-effective routine imaging technique in FUO by avoiding unnecessary
      investigations and reducing the duration of hospitalization.

PMID- 29452616
TI  - Tuberculosis.
AB  - Tuberculosis (TB) is currently the world's leading cause of infectious mortality.
      Imaging plays an important role in the management of this disease. The complex
      immune response of the human body to Mycobacterium tuberculosis results in a wide
      array of clinical manifestations, making clinical and radiological diagnosis
      challenging. 18F-FDG-PET/CT is very sensitive in the early detection of TB in
      most parts of the body; however, the lack of specificity is a major limitation.
      18F-FDG-PET/CT images the whole body and provides a pre-therapeutic metabolic map
      of the infection, enabling clinicians to accurately assess the burden of disease.
      It enables the most appropriate site of biopsy to be selected, stages the
      infection, and detects disease in previously unknown sites. 18F-FDG-PET/CT has
      recently been shown to be able to identify a subset of patients with latent TB
      infection who have subclinical disease. Lung inflammation as detected by 18F-FDG
      PET/CT has shown promising signs that it may be a useful predictor of progression
      from latent to active infection. A number of studies have identified imaging
      features that might improve the specificity of 18F-FDG-PET/CT at some sites of
      extrapulmonary TB. Other PET tracers have also been investigated for their use in
      TB, with some promising results. The potential role and future perspectives of
      PET/CT in imaging TB is considered. Literature abounds on the very important role
      of 18F-FDG-PET/CT in assessing therapy response in TB. The use of 18F-FDG for
      monitoring response to treatment is addressed in a separate review.

PMID- 29452617
TI  - Imaging of Spondylodiscitis.
AB  - Spondylodiscitis is an infection of the vertebral body or disc and may also
      involve the epidural space, posterior elements, and paraspinal soft tissues. It
      is a cause of morbidity and mortality, and warrants early diagnosis and prompt
      treatment. Diagnosis can be difficult because of nonspecific signs and symptoms.
      Magnetic resonance imaging is sensitive and specific and is the imaging modality
      of choice for spondylodiscitis. Gadolinium contrast can show the extent of soft
      tissue and bone phlegmon and abscess. The test is less useful for evaluating
      treatment response. When magnetic resonance imaging cannot be performed or is not
      diagnostic, radionuclide imaging is a useful alternative. Although bone
      scintigraphy frequently is used as a screening test, false-negative results can
      occur, especially in the elderly. This test is not useful for detecting soft
      tissue infections that accompany or mimic spondylodiscitis. Gallium-67 citrate
      improves the specificity of the bone scan, can detect infection earlier than the
      bone scan, may be more sensitive, especially in elderly patients, and identifies
      accompanying soft tissue infection. Performing SPECT and SPECT/CT improves
      accuracy. The 2- to 3-day delay between radiopharmaceutical administration and
      the relatively poor image quality are significant disadvantages of gallium-67.
      Indium-111 biotin, alone or in combination with streptavidin, accurately
      diagnoses spondylodiscitis; unfortunately, this agent is not widely available.
      Currently, 18F-FDG imaging is the radionuclide test of choice for
      spondylodiscitis. The procedure, which is completed in a single session, is
      sensitive, has a high negative predictive value, and reliably differentiates
      degenerative from infectious vertebral body end plate abnormalities. In
      comparative investigations, 18F-FDG has outperformed bone and gallium-67 imaging.
      Preliminary data suggest that 18F-FDG may be able to provide an objective means
      to measure response to treatment. Gallium-68 citrate and 99mTc-radiolabeled
      antimicrobial peptides have been investigated, but their role in spondylodiscitis
      has yet to be established.

PMID- 29452618
TI  - Radionuclide Imaging of Infection and Inflammation in Children: a Review.
AB  - With the exception of radiolabeled monoclonal antibodies, antibody fragments and
      radiolabeled peptides which have seen little application in the pediatric
      population, the nuclear medicine imaging procedures used in the evaluation of
      infection and inflammation are the same for both adults and children. These
      procedures include (1) either a two- or a three-phase bone scan using technetium
      99m methylene diphosphonate; (2) Gallium 67-citrate; (3) in vitro radiolabeled
      white blood cell imaging (using 111Indium-oxine or 99mTechnetium hexamethyl
      propylene-amine-oxime-labeled white blood cells); and (4) hybrid imaging with 18F
      FDG. But children are not just small adults. Not only are the disease processes
      encountered in children different from those in adults, but there are
      developmental variants that can mimic, but should not be confused with,
      pathology. This article discusses some of the differences between adults and
      children with osteomyelitis, illustrates several of the common developmental
      variants that can mimic disease, and, finally, focuses on the increasing use of
      18F-FDG PET/CT in the diagnosis and response monitoring of children with
      infectious and inflammatory processes. The value of and need for pediatric
      specific imaging protocols are reviewed.

PMID- 29452619
TI  - Monitoring Response to Therapy.
AB  - Monitoring response to treatment is a key element in the management of infectious
      diseases, yet controversies still persist on reliable biomarkers for noninvasive
      response evaluation. Considering the limitations of invasiveness of most
      diagnostic procedures and the issue of expression heterogeneity of pathology,
      molecular imaging is better able to assay in vivo biologic processes
      noninvasively and quantitatively. The usefulness of 18F-FDG-PET/CT in assessing
      treatment response in infectious diseases is more promising than for conventional
      imaging. However, there are currently no clinical criteria or recommended imaging
      modalities to objectively evaluate the effectiveness of antimicrobial treatment.
      Therapeutic effectiveness is currently gauged by the patient's subjective
      clinical response. In this review, we present the current studies for monitoring
      treatment response, with a focus on Mycobacterium tuberculosis, as it remains a
      major worldwide cause of morbidity and mortality. The role of molecular imaging
      in monitoring other infections including spondylodiscitis, infected prosthetic
      vascular grafts, invasive fungal infections, and a parasitic disease is
      highlighted. The role of functional imaging in monitoring lipodystrophy
      associated with highly active antiretroviral therapy for human immunodeficiency
      virus is considered. We also discuss the key challenges and emerging data in
      optimizing noninvasive response evaluation.

PMID- 29452621
TI  - Letter from the Editors.

PMID- 29452622
TI  - Letter from the Guest Editor.

PMID- 29452623
TI  - Currently Available Radiopharmaceuticals for Imaging Infection and the Holy
      Grail.
AB  - Infection is ubiquitous. However, its management is challenging for both the
      patients and the health-care providers. Scintigraphic imaging of infection dates
      back nearly half a century. The advances in our understanding of the
      pathophysiology of disease at cellular and molecular levels have paved the way to
      the development of a large number of radiopharmaceuticals for scintigraphic
      imaging of infection. These include radiolabeling of blood elements such as serum
      proteins, white blood cells (WBCs), and cytokines, to name a few. Infectious foci
      have also been imaged using a radiolabeled sugar molecule by taking advantage of
      increased metabolic activity in the infectious lesions. Literature over the years
      has well documented that none of the radiopharmaceuticals and associated
      procedures that facilitate imaging infection are flawless and acceptable without
      a compromise. As a result, only a few compounds such as 99mTc
      hexamethylpropyleneamineoxime, 18F-FDG, the oldest but still considered as a gold
      standard 111In-oxine, and, yes, even 67Ga-citrate in some countries, have
      remained in routine clinical practice. Nonetheless, the interest of scientists
      and physicians to improve the approaches to imaging and to the management of
      infection is noteworthy. These approaches have paved the way for the development
      of numerous, innovative radiopharmaceuticals to label autologous WBCs ex vivo or
      even those that could be injected directly to image infection or inflammation
      without direct involvement of WBCs. In this review, we briefly describe these
      agents with their pros and cons and place them together for future reference.

PMID- 29452620
TI  - Pathogen-Specific Bacterial Imaging in Nuclear Medicine.
AB  - When serious infections are suspected, patients are often treated empirically
      with broad-spectrum antibiotics while awaiting results that provide information
      on the bacterial class and species causing the infection, as well as drug
      susceptibilities. For deep-seated infections, these traditional diagnostic
      techniques often rely on tissue biopsies to obtain clinical samples which can be
      expensive, dangerous, and has the potential of sampling bias. Moreover, these
      procedures and results can take several days and may not always provide reliable
      information. This combination of time and effort required for proper antibiotic
      selection has become a barrier leading to indiscriminate broad-spectrum
      antibiotic use. Exposure to nosocomial infections and indiscriminate use of broad
      spectrum antibiotics are responsible for promoting bacterial drug-resistance
      leading to substantial morbidity and mortality, especially in hospitalized and
      immunosuppressed patients. Therefore, early diagnosis of infection and targeted
      antibiotic treatments are urgently needed to reduce morbidity and mortality
      caused by bacterial infections worldwide. Reliable pathogen-specific bacterial
      imaging techniques have the potential to provide early diagnosis and guide
      antibiotic treatments.

PMID- 29452624
TI  - From the Editor's Perspective....

PMID- 29452625
TI  - Knowledge regarding noncytotoxic medication extravasation among registered nurses
      working in western Saudi Arabia.
AB  - Extravasation and infiltration are among the most common intravenous therapy
      complications. For noncytotoxic agents, the incidence of extravasation remains
      unknown. There has been little research into extravasation due to ethical
      considerations limiting controlled research; most evidences are based on small,
      uncontrolled trials or case reports. The purpose of this study was to assess the
      knowledge level regarding noncytotoxic medications extravasation and its
      associated factors among staff nurses.A descriptive correlational design using
      self-administered questionnaire was employed. A convenience sample of 387 nurses
      completed a questionnaire about noncytotoxic medication extravasation.
      Statistical Package for Social Sciences version 21 was used to analyze data by
      applying the chi-square test, t test, and the Mann-Whitney test to assess the
      knowledge difference between open and closed units' nurses.The results indicate
      that only 19.6% of nurses have a good knowledge about noncytotoxic medications
      extravasation. There was consistently poor staff knowledge regarding noncytotoxic
      medications extravasation. Although the closed units' nurses reported relatively
      higher level of knowledge than open units' nurses, their level of knowledge still
      inadequate. Health care organizations must consider developing specific policies
      regarding extravasation. Closed and open units' nurses should be enrolled in
      special education programs to improve their level of knowledge regarding
      noncytotoxic medication extravasation.

PMID- 29452627
TI  - Case series of 18 patients with lower extremity wounds treated with a
      concentrated surfactant-based gel dressing.
AB  - The purpose of this case series was to assess the performance of a concentrated
      surfactant-based gel (CSG) dressing on 18 patients in the outpatient setting over
      4 weeks. Wounds selected were full thickness, had been presented for greater than
      4 weeks, and were located on the lower extremities. Patients were given the CSG
      dressing and instructed on its use. On follow-up clinic visits, the wound was
      assessed, measurements were obtained, Pressure Ulcer Scale for Healing (PUSH)
      Tool scores completed, and satisfaction with the dressing was solicited.
      Individual analysis of each subject's wound was conducted to determine if there
      was a healing trend over time with a decrease in total PUSH score. Descriptive
      statistics were used to analyze the results. Eighteen patients participated in
      this case series involving 9 women and 9 men with a mean age of 66 years (range
      from 52 to 91). All 18 of the patients had a primary diagnosis of peripheral
      vascular disease with 7 patients having venous leg ulcers and 11 patients with
      lower extremity arterial ulcers. The mean Total PUSH score before the CSG
      dressing was applied was 10.7 (range from 5 to 15) (standard deviation [SD] 3.09)
      and posttreatment was 8.3 (range from 0 to 14) (SD 4). All 18 patients had a
      decrease in their pretreatment score from the first clinic visit compared with
      the posttreatment PUSH Tool score, indicating that the CSG dressing may be an
      effective dressing in the management of lower extremity wounds.

PMID- 29452626
TI  - Translation of an evidence-based therapeutic exercise program for patients with
      peripheral artery disease.
AB  - The purpose of this study was to implement and evaluate quality outcomes
      including referral, enrollment, and completion rates of a new peripheral artery
      disease (PAD)-specific supervised exercise therapy (SET) program within a
      preexisting clinical exercise wellness program and to evaluate the clinical
      effectiveness and patient-centered outcomes derived from 12 weeks of PAD-specific
      SET. Recruited participants completed an individualized, minimally supervised,
      PAD-specific SET program based on the AHA-ACC guidelines. Exercise workloads
      (metabolic equivalents of task [METs]) were tracked and evaluated throughout the
      program. Short Physical Performance Battery, 6-minute walk test (6MWT) Walking
      Impairment Questionnaire, Short-Form 36 (SF-36), and Peripheral Artery Disease
      Quality of Life Questionnaire (PADQOL) were assessed before and after the
      program. Paired t-tests were used to examine differences between baseline and
      follow-up outcome variables. On average, participants (n = 46) attended 23
      (standard deviation [SD] 12.9) out of the possible 36 training sessions, for a
      64% attendance rate. Among participants who used treadmill walking as the primary
      mode of exercise (n = 40), the overall mean MET level just prior to program
      completion was 3.79 (SD 1.49), which represented an increase of 0.92 (34%) METs
      compared to baseline (P < .001). Total distance on the 6MWT increased 115 (11%)
      feet (P = .011), which is considered a clinically meaningful improvement.
      Significant improvements were noted in the PADQOL: symptoms and limitations in
      physical functioning (P = .007). This study demonstrates that a minimally staffed
      PAD-specific SET program can improve functional performance in patients with
      claudication due to PAD and serves as a foundation to help build a clinically
      effective, Centers for Medicare and Medicaid reimbursed PAD-specific
      rehabilitation program.

PMID- 29452628
TI  - An integrative review of peer support for patients undergoing major limb
      amputation.
AB  - Medical literature is replete with evidence regarding physical rehabilitation of
      the amputee; however, scant attention has been paid to psychological
      rehabilitation. The objective was to perform an integrative review of the
      published medical evidence regarding amputee peer support in the civilian
      population and provide an evidence-based clinical practice recommendation. This
      study was based on an exhaustive examination of the civilian amputee peer support
      medical evidence, bibliographic search, and on the experience of the authors when
      performing this integrative review. Our search uncovered 10 published peer
      reviewed pieces of medical evidence including one level III retrospective case
      controlled trial, two level IV case series, and seven level V expert opinions.
      Given the totality of the published evidence, albeit limited, in favor of amputee
      peer support, an abundance of unpublished anecdotal evidence, virtually no
      potential risk of harm, and low cost, it seems reasonable to recommend
      incorporating a preoperative and/or postoperative peer visit in clinical
      protocols for all patients incurring a major limb amputation.

PMID- 29452629
TI  - Continuous betadine-bacitracin irrigation for vascular graft infections: A case
      series.
AB  - The aim of the study was to conduct a retrospective chart review of patients who
      underwent betadine/bacitracin continuous irrigation (BBCI) for vascular graft
      infections (VGIs) to review its use as a treatment option. A retrospective chart
      review from 2013 to 2017 was conducted of patients with VGIs that were treated
      with BBCI postremoval of the infected graft. The BBCI is a continuous infusion of
      0.25% betadine in normal saline at 0.3 mL/kg/h for 48 hours then followed by
      bacitracin infusion with a concentration of 50,000 units bacitracin/per liter
      normal saline at 0.3 mL/kg/h for 72 hours. Descriptive statistics were used to
      describe the sample. The nine adult patients who received postoperative BBCI had
      an age range of 30-81 years, with average age of 58.8 years. Five of the subjects
      were females with four males. A total of nine patients with groin infections were
      identified, with two aortobifemoral bypasses, two axillofemoral bypasses, three
      femoral-femoral bypasses, one femoral artery pseudoaneurysm repair with Dacron
      patch, and one common femoral endarterectomy with Dacron patch. VGIs were
      identified from 10 days up to 72 months from the original vascular procedure. Six
      patients had negative wound cultures, while two had wound cultures positive for
      methicillin-resistant Staphylococcus aureus and one patient had positive culture
      for Escherichia coli. The length of time of BBCI ranged from 48 to 84 hours with
      average of 57.6 hours (standard deviation [SD] = 12.7 hours). The length of time
      of the bacitracin irrigation ranged from 30 to 72 hours with average of 48.4
      hours (SD = 14.9 hours). All patients healed their groin wounds except for an 81
      year-old patient with aortobifemoral bypass graft who developed ischemic bowel
      and expired. Patients received at least 6 weeks of intravenous antibiotics
      followed by oral antibiotic suppression therapy for life. VGIs are a devastating
      complication associated with a high morbidity. BBCI provides an option for
      antiseptic irrigation of the vascular graft site postgraft removal to promote
      wound closure.

PMID- 29452630
TI  - Review of article: Predictive ability of the Society for Vascular Surgery Wound,
      Ischemia, and foot Infection (WIfI) classification system following
      infrapopliteal endovascular interventions for critical limb ischemia. Darling,
      J.D., McCallum, J.C., Soden, P.A., Meng, Y., Wyers, M.C., Hamdan, A.D., Verhagen,
      H.J. & Schermerhorn, M.L. Journal of Vascular Surgery 2016; 64:616-22.

PMID- 29452632
TI  - SOARD Category 1 CME Credit Featured Articles, Volume 14, February 2018retain-->.

PMID- 29452631
TI  - The evaluation of the implementation of the vascular preventative bundle and
      development of suggested interventions for improvement and sustainability.
AB  - Postoperative infections can complicate patient care and increase health care
      costs. A vascular preventative bundle was implemented at a large
      teaching/research intensive hospital to decrease surgical site infections (SSIs)
      with vascular surgery patients. The aim of this study was to measure fidelity to
      the bundle and determine if implementation of the vascular SSI bundle reduced the
      rate of SSIs. Three periods of data were collected, and they are identified as
      preimplementation (period 1), early implementation (period 2), and
      postimplementation (period 3). There were 711 patients for all three periods,
      approximately equally distributed in the periods. The use of preoperative hair
      clippings, chlorhexidine (CHG) wipes, and appropriate antibiotics showed the
      greatest improvement from preimplementation to early implementation. All three
      measures showed significant improvements in fidelity. For appropriate
      antibiotics, the fidelity was the highest and showed the largest improvement
      compared to the other measures. The performance of clippings preoperatively and
      using CHG wipes improved significantly. Evidence-based interventions have been
      recommended to support the implementation and sustainability of the bundle. The
      infection rate between preop and postperiod was not statistically different.

PMID- 29452633
TI  - Inflammation NODs to Antagonists of RIP2-XIAP Interaction.
AB  - While innate immunity is crucial for host defense, dysregulated signaling
      activation leads to pathological inflammation. In this issue of Molecular Cell,
      Goncharov et al. (2018) present a strategy to combat inflammatory diseases by
      disrupting RIP2-XIAP interaction in NOD2-mediated signaling.

PMID- 29452634
TI  - m6A and eIF2alpha-p Team Up to Tackle ATF4 Translation during Stress.
AB  - While m6A modification of mRNAs is now known to be widespread, the cellular roles
      of this modification remain largely mysterious. In this issue of Molecular Cell,
      Zhou et al. (2018) show that m6A modification unexpectedly contributes to the
      established uORF- and eIF2alpha-p-dependent mechanism of ATF4 translational
      regulation in response to stress.

PMID- 29452635
TI  - The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic
      Activities Upstream of the Drosophila Toll Pathway.
AB  - Microbial or endogenous molecular patterns as well as pathogen functional
      features can activate innate immune systems. Whereas detection of infection by
      pattern recognition receptors has been investigated in details, sensing of
      virulence factors activities remains less characterized. In Drosophila, genetic
      evidences indicate that the serine protease Persephone belongs to a danger
      pathway activated by abnormal proteolytic activities to induce Toll signaling.
      However, neither the activation mechanism of this pathway nor its specificity has
      been determined. Here, we identify a unique region in the pro-domain of
      Persephone that functions as bait for exogenous proteases independently of their
      origin, type, or specificity. Cleavage in this bait region constitutes the first
      step of a sequential activation and licenses the subsequent maturation of
      Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish
      Persephone itself as an immune receptor able to sense a broad range of microbes
      through virulence factor activities rather than molecular patterns.

PMID- 29452636
TI  - Disruption of XIAP-RIP2 Association Blocks NOD2-Mediated Inflammatory Signaling.
AB  - Inflammatory responses mediated by NOD2 rely on RIP2 kinase and ubiquitin ligase
      XIAP for the activation of nuclear factor kappaB (NF-kappaB), mitogen-activated
      protein kinases (MAPKs), and cytokine production. Herein, we demonstrate that
      selective XIAP antagonism blocks NOD2-mediated inflammatory signaling and
      cytokine production by interfering with XIAP-RIP2 binding, which removes XIAP
      from its ubiquitination substrate RIP2. We also establish that the kinase
      activity of RIP2 is dispensable for NOD2 signaling. Rather, the conformation of
      the RIP2 kinase domain functions to regulate binding to the XIAP-BIR2 domain.
      Effective RIP2 kinase inhibitors block NOD2 signaling by disrupting RIP2-XIAP
      interaction. Finally, we identify NOD2 signaling and XIAP-dependent
      ubiquitination sites on RIP2 and show that mutating these lysine residues
      adversely affects NOD2 pathway signaling. Overall, these results reveal a
      critical role for the XIAP-RIP2 interaction in NOD2 inflammatory signaling and
      provide a molecular basis for the design of innovative therapeutic strategies
      based on XIAP antagonists and RIP2 kinase inhibitors.

PMID- 29452637
TI  - Ubiquitin-Mediated Regulation of RIPK1 Kinase Activity Independent of IKK and
      MK2.
AB  - Tumor necrosis factor (TNF) can drive inflammation, cell survival, and death.
      While ubiquitylation-, phosphorylation-, and nuclear factor kappaB (NF-kappaB)
      dependent checkpoints suppress the cytotoxic potential of TNF, it remains unclear
      whether ubiquitylation can directly repress TNF-induced death. Here, we show that
      ubiquitylation regulates RIPK1's cytotoxic potential not only via activation of
      downstream kinases and NF-kB transcriptional responses, but also by directly
      repressing RIPK1 kinase activity via ubiquitin-dependent inactivation. We find
      that the ubiquitin-associated (UBA) domain of cellular inhibitor of apoptosis
      (cIAP)1 is required for optimal ubiquitin-lysine occupancy and K48 ubiquitylation
      of RIPK1. Independently of IKK and MK2, cIAP1-mediated and UBA-assisted
      ubiquitylation suppresses RIPK1 kinase auto-activation and, in addition, marks it
      for proteasomal degradation. In the absence of a functional UBA domain of cIAP1,
      more active RIPK1 kinase accumulates in response to TNF, causing RIPK1 kinase
      mediated cell death and systemic inflammatory response syndrome. These results
      reveal a direct role for cIAP-mediated ubiquitylation in controlling RIPK1 kinase
      activity and preventing TNF-mediated cytotoxicity.

PMID- 29452638
TI  - NADH Shuttling Couples Cytosolic Reductive Carboxylation of Glutamine with
      Glycolysis in Cells with Mitochondrial Dysfunction.
AB  - The bioenergetics and molecular determinants of the metabolic response to
      mitochondrial dysfunction are incompletely understood, in part due to a lack of
      appropriate isogenic cellular models of primary mitochondrial defects. Here, we
      capitalize on a recently developed cell model with defined levels of m.8993T>G
      mutation heteroplasmy, mTUNE, to investigate the metabolic underpinnings of
      mitochondrial dysfunction. We found that impaired utilization of reduced
      nicotinamide adenine dinucleotide (NADH) by the mitochondrial respiratory chain
      leads to cytosolic reductive carboxylation of glutamine as a new mechanism for
      cytosol-confined NADH recycling supported by malate dehydrogenase 1 (MDH1). We
      also observed that increased glycolysis in cells with mitochondrial dysfunction
      is associated with increased cell migration in an MDH1-dependent fashion. Our
      results describe a novel link between glycolysis and mitochondrial dysfunction
      mediated by reductive carboxylation of glutamine.

PMID- 29452639
TI  - Mitochondrial MDM2 Regulates Respiratory Complex I Activity Independently of p53.
AB  - Accumulating evidence indicates that the MDM2 oncoprotein promotes tumorigenesis
      beyond its canonical negative effects on the p53 tumor suppressor, but these p53
      independent functions remain poorly understood. Here, we show that a fraction of
      endogenous MDM2 is actively imported in mitochondria to control respiration and
      mitochondrial dynamics independently of p53. Mitochondrial MDM2 represses the
      transcription of NADH-dehydrogenase 6 (MT-ND6) in vitro and in vivo, impinging on
      respiratory complex I activity and enhancing mitochondrial ROS production.
      Recruitment of MDM2 to mitochondria increases during oxidative stress and
      hypoxia. Accordingly, mice lacking MDM2 in skeletal muscles exhibit higher MT-ND6
      levels, enhanced complex I activity, and increased muscular endurance in mild
      hypoxic conditions. Furthermore, increased mitochondrial MDM2 levels enhance the
      migratory and invasive properties of cancer cells. Collectively, these data
      uncover a previously unsuspected function of the MDM2 oncoprotein in mitochondria
      that play critical roles in skeletal muscle physiology and may contribute to
      tumor progression.

PMID- 29452641
TI  - Cdc48/VCP Promotes Chromosome Morphogenesis by Releasing Condensin from Self
      Entrapment in Chromatin.
AB  - The morphological transformation of amorphous chromatin into distinct chromosomes
      is a hallmark of mitosis. To achieve this, chromatin must be compacted and
      remodeled by a ring-shaped enzyme complex known as condensin. However, the
      mechanistic basis underpinning condensin's role in chromosome remodeling has
      remained elusive. Here we show that condensin has a strong tendency to trap
      itself in its own reaction product during chromatin compaction and yet is capable
      of interacting with chromatin in a highly dynamic manner in vivo. To resolve this
      apparent paradox, we identified specific chromatin remodelers and AAA-class
      ATPases that act in a coordinated manner to release condensin from chromatin
      entrapment. The Cdc48 segregase is the central linchpin of this regulatory
      mechanism and promotes ubiquitin-dependent cycling of condensin on mitotic
      chromatin as well as effective chromosome condensation. Collectively, our results
      show that condensin inhibition by its own reaction product is relieved by
      forceful enzyme extraction from chromatin.

PMID- 29452640
TI  - Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation
      Initiation and Maintenance of Formylmethionyl-tRNAs.
AB  - Upon glucose restriction, eukaryotic cells upregulate oxidative metabolism to
      maintain homeostasis. Using genetic screens, we find that the mitochondrial
      serine hydroxymethyltransferase (SHMT2) is required for robust mitochondrial
      oxygen consumption and low glucose proliferation. SHMT2 catalyzes the first step
      in mitochondrial one-carbon metabolism, which, particularly in proliferating
      cells, produces tetrahydrofolate (THF)-conjugated one-carbon units used in
      cytoplasmic reactions despite the presence of a parallel cytoplasmic pathway.
      Impairing cytoplasmic one-carbon metabolism or blocking efflux of one-carbon
      units from mitochondria does not phenocopy SHMT2 loss, indicating that a
      mitochondrial THF cofactor is responsible for the observed phenotype. The enzyme
      MTFMT utilizes one such cofactor, 10-formyl THF, producing formylmethionyl-tRNAs,
      specialized initiator tRNAs necessary for proper translation of mitochondrially
      encoded proteins. Accordingly, SHMT2 null cells specifically fail to maintain
      formylmethionyl-tRNA pools and mitochondrially encoded proteins, phenotypes
      similar to those observed in MTFMT-deficient patients. These findings provide a
      rationale for maintaining a compartmentalized one-carbon pathway in mitochondria.

PMID- 29452645
TI  - Patient-Reported Outcomes in Esophageal Diseases.

PMID- 29452643
TI  - Combinatorial CRISPR-Cas9 Metabolic Screens Reveal Critical Redox Control Points
      Dependent on the KEAP1-NRF2 Regulatory Axis.
AB  - The metabolic pathways fueling tumor growth have been well characterized, but the
      specific impact of transforming events on network topology and enzyme
      essentiality remains poorly understood. To this end, we performed combinatorial
      CRISPR-Cas9 screens on a set of 51 carbohydrate metabolism genes that represent
      glycolysis and the pentose phosphate pathway (PPP). This high-throughput
      methodology enabled systems-level interrogation of metabolic gene dispensability,
      interactions, and compensation across multiple cell types. The metabolic impact
      of specific combinatorial knockouts was validated using 13C and 2H isotope
      tracing, and these assays together revealed key nodes controlling redox
      homeostasis along the KEAP-NRF2 signaling axis. Specifically, targeting KEAP1 in
      combination with oxidative PPP genes mitigated the deleterious effects of these
      knockouts on growth rates. These results demonstrate how our integrated
      framework, combining genetic, transcriptomic, and flux measurements, can improve
      elucidation of metabolic network alterations and guide precision targeting of
      metabolic vulnerabilities based on tumor genetics.

PMID- 29452646
TI  - Corrigendum to "Insights into molecular and cellular mechanisms of hormonal
      actions on fish ion regulation derived from the zebrafish model" [Gen. Comp.
      Endocrinol. 251 (2017) 12-20].

PMID- 29452642
TI  - The Yeast INO80 Complex Operates as a Tunable DNA Length-Sensitive Switch to
      Regulate Nucleosome Sliding.
AB  - The yeast INO80 chromatin remodeling complex plays essential roles in regulating
      DNA damage repair, replication, and promoter architecture. INO80's role in these
      processes is likely related to its ability to slide nucleosomes, but the
      underlying mechanism is poorly understood. Here we use ensemble and single
      molecule enzymology to study INO80-catalyzed nucleosome sliding. We find that the
      rate of nucleosome sliding by INO80 increases ~100-fold when the flanking DNA
      length is increased from 40 to 60 bp. Furthermore, once sliding is initiated,
      INO80 moves the nucleosome rapidly at least 20 bp without pausing to re-assess
      flanking DNA length, and it can change the direction of nucleosome sliding
      without dissociation. Finally, we show that the Nhp10 module of INO80 plays an
      auto-inhibitory role, tuning INO80's switch-like response to flanking DNA. Our
      results indicate that INO80 is a highly processive remodeling motor that is
      tightly regulated by both substrate cues and non-catalytic subunits.

PMID- 29452648
TI  - Insufficient evidence of the superiority of near-infrared light transillumination
      over bite-wing digital radiograph for detecting early interproximal carious
      lesions.

PMID- 29452649
TI  - Large proportion of impressions for fixed prosthesis had errors, but we cannot
      infer how this would affect outcomes important to patients.

PMID- 29452647
TI  - Genetic markers of nasolabial morphology.

PMID- 29452650
TI  - Short-term use of alcohol-containing mouthrinse does not worsen xerostomia
      compared with alcohol-free mouthrinse.

PMID- 29452651
TI  - Melatonin as an adjunct to autogenous bone grafts may result in small benefits in
      probing depth, marginal bone loss, and gingival index of sites with immediate
      implants.

PMID- 29452652
TI  - ?

PMID- 29452653
TI  - [Post-inflammatory hyperpigmentation].
AB  - Post-inflammatory hyperpigmentation (PIH) is a hyperpigmentation of the skin
      occurring after and sometimes during an inflammatory process. Although more
      frequent in dark skinned individuals, PIH can be observed in any type of skin and
      at all ages. In most case a strong impact on the quality of life of affected
      individuals is observed. The pathophysiology of PIH remains largely unknown. The
      activation of the melanocytes occurs in the first week following the inflammation
      emphasizing the crucial role of early preventive measures. Photoprotection with
      balanced UVA and UVB protection is required. Visible light could also play a role
      in PIH but this remains to be demonstrated. Healing topics with anti-inflammatory
      properties are of interest after a skin procedure. When the risk of PIH is high
      or when PIH occurs, topical steroids remains the gold standard approach.

PMID- 29452654
TI  - [Dermatosurgery and other interventional techniques in dermatology: a more than
      2000 year-history].
AB  - Surgical dermatology has probably existed since the first steps of antique
      medicine, especially for cutaneous cancer excision and wound reparation.
      Wonderful descriptions of surgical flaps can be found in the Encyclopedy of
      Celse, a Roman doctor living in the first century AC. Major progresses in local
      anesthesy were achieved at the end of the XIXth century, allowing the first
      dermatologists of the XXth century to perform biopsies and cutaneous surgery with
      a good control of patient's pain. Electricity was introduced in medicine at the
      end of the XIXth century, and our ancestors dermatologists used it for
      electrocoagulation, cauterization and electric hair removal. In the " Pratique
      dermatologique ", the first encyclopedy of dermatology published in 1900, many
      chapters show how important instrumental and surgical dermatology was. Pigmentary
      changes induced by surgery and other procedures were probably well known then but
      were less important than troubles due to scarring, which are mentioned in the
      early literature. Spontaneous or post-interventional cheloids are well discussed
      in the early works of Alibert, in the years 1810. This article shows that
      surgical dermatology is far more ancient than the creation of societies dedicated
      to it in the XXth century.

PMID- 29452655
TI  - [How to optimize scarring in dermatologic surgery?]
AB  - Scarring is the response elicited by the skin surface to injury and loss of
      tissue material. Wound healing takes place through a complex natural repair
      system consisting of vascular, inflammatory and proliferative phenomena, followed
      by a remodelling and cell apoptosis phase. This incredible repair system is
      inevitable, but sometimes unpredictable due to individual differences based on
      multiple factors. The scar is the objective criterion of a skin surgery, both for
      the patient and the dermsurgeon. It is therefore crucial to establish with the
      patient during the preoperative consultation, the size and positioning of the
      expected scar, taking into account the oncologic, anatomic and surgical
      constraints. Scars can ideally blend into normal skin, but may also give rise to
      various abnormalities. We can manage and prevent these abnormalities by mastering
      initial inflammation, that may induce hyperpigmentation and hypertrophy. Early
      massage using cortocosteroid topic or anti-inflammatory moisturizers may be
      effective. Random individual scarring may be minimized by a dynamic personalized
      accompanying scarring.

PMID- 29452656
TI  - [Optimization of the healing process after laser procedure, except
      photorejuvenation].
AB  - The use of Lasers in dermatology implies a crucial follow-up in order to optimize
      the final result and avoid any side effects. With the use of ablative laser
      devices, the initial phase is characterized by the development of crusts. These
      crusts necessitate the application of sterile ointments (regularly repeated
      throughout the day) as well as an antibiotic ointment two times a day. In a
      second step, comes a secondary inflammatory state, in the dermis, which is
      generally observed at the outset of all other laser treatments. The main purpose
      is to avoid it from being too sustained over time, but also to prevent the
      occurrence of post inflammatory hyperpigmentation. Obviously, a solar eviction
      will be strongly recommended. The risk being maximized with dark phototypes, the
      choice of the Laser, as well as its specific parameters will be specific and
      decisive.

PMID- 29452657
TI  - [Post-inflammatory hyperpigmentation occuring after cosmetic procedures].
AB  - A post-inflammatory hyperpigmentation (PIHP) can occur after cosmetic procedures
      such as chemical peels and lasers. Patients must be informed about this risk.
      Precautionary measures before, during and after the procedure can prevent or
      reduce the risk of PIHP. These procedures should not be done in summer on
      suntanned skin and patients have to be aware of the importance of an effective
      photoprotection. The PIHP occurs more frequently on dark-skinned patients, in
      Asians as well as in women with melasma history. In these cases, risk/benefit
      assessment of the cosmetic procedure is required: no risky procedure in patients
      at risk! PIHP can also be related to technical errors such as too high
      concentration or too long exposure time during peel procedure as well as
      excessive threshold fluences during laser procedure. If many therapies for PIHP
      damages can be proposed, patients feel frequently that they are not as quickly
      effective as they would like. Patients must be reassured as many PIHP resolve
      spontaneously. If photoprotection is always required, it is also possible to
      accelerate the pigmentation's clearing using the Kligman trio or the numerous
      topical lightening agents targeting several steps of the hyperpigmentation
      process. More invasive and expensive therapies such as peels, lasers, IPL or
      radiofrequency might be used for refractory cases. As a pigmentary relapse might
      occur after these procedures, the traditional Kligman trio should be always
      considered.

PMID- 29452658
TI  - Corrigendum to "Quantification of type II procollagen splice forms using
      alternative transcript-qPCR (AT-qPCR)" [Matrix Biol. 31(2012) 412-420].

PMID- 29452659
TI  - Indolent lymphomas.

PMID- 29452660
TI  - Novel therapies for relapsed/refractory mantle cell lymphoma.
AB  - Mantle cell lymphoma is an aggressive Non-Hodgkin's lymphoma that is considered
      incurable with standard therapies. Most patients treated with frontline
      immunochemotherapy relapse within a few years and do not usually respond to
      salvage chemotherapy. Persistent activation of the B-cell receptor pathway is
      critical to the pathogenesis of mantle cell lymphoma. Inhibition of Bruton's
      tyrosine kinase, an essential B-cell receptor pathway component with ibrutinib
      has shown clinical activity and has changed how MCL is treated in the
      relapsed/refractory setting. However, resistance to ibrutinib is common and
      response is limited. Novel agents targeting the B-cell receptor pathway along
      with therapies outside of the pathway will be reviewed in this article. Ongoing
      and future studies will better define how these agents should be utilized in the
      ever-changing treatment landscape of mantle cell lymphoma.

PMID- 29452661
TI  - Risk stratification in follicular lymphoma.
AB  - Advances in the understanding of FL biology, molecular characteristics and
      clinical risk factors are further highlighting the heterogeneity of this disease.
      Historically used prognostic factors were broadly based on clinical and
      laboratory features at the time of diagnosis. However novel prognostic factors
      are emerging that can be studied at the time of diagnosis, and relapse, and use a
      variety of tools including gene alterations and diagnostic imaging. These novel
      discoveries are being implemented into daily practice with the ultimate goal of
      providing a precise, individualized approach to every patient with FL.

PMID- 29452662
TI  - Pathogenesis of follicular lymphoma.
AB  - Follicular lymphoma (FL) is presented as a germinal centre B cell lymphoma that
      is characterized by an indolent clinical course, but remains - paradoxically -
      largely incurable to date. The last years have seen significant progress in our
      understanding of FL lymphomagenesis, which is a multi-step process beginning in
      the bone marrow with the hallmark t(14;18)(q32;q21) translocation. The
      pathobiology of FL is complex and combines broad somatic changes at the level of
      both the genome and the epigenome, the latter evidenced by highly recurrent
      mutations in chromatin-modifying genes such as KMT2D and CREBBP. While the
      importance of the FL microenvironment has since long been well understood, it has
      become evident that somatic lesions within tumour cells re-educate normal immune
      and stromal cells to their advantage. Enhanced understanding of FL pathogenesis
      is currently leading to refined therapeutic targeting of perturbed biology,
      paving the way for precision medicine in this lymphoma subtype.

PMID- 29452663
TI  - Management of untreated advanced stage follicular lymphoma: Role of patient
      discernment.
AB  - Follicular lymphoma is the most common indolent non-Hodgkin lymphoma. Advanced
      stage disease is common at diagnosis. The timing of treatment for follicular
      lymphoma is best approached by considering the combination of presence or absence
      of symptoms along with estimation of tumor burden. Upfront treatment strategies
      should take into initial presentation variables, pace of disease progression and
      goals of care after discussion with the patient. Treatment approaches remain
      diverse and patient discernment is paramount.

PMID- 29452664
TI  - The role of stem cell transplantation in follicular lymphoma.
AB  - With the introduction of novel treatments paradigms to if or when to use
      transplantation strategies for patients with follicular lymphoma have changed
      substantially. Autologous transplantation has been intensively evaluated as
      consolidation after first induction treatment with positive effects, however the
      introduction of Rituximab led to comparable improvements and HDT has been moved
      to relapse treatment. In this indication HDT was frequently use already at first
      relapse, but now is dominantly used in patients with a highrisk profile, e.g.
      failure of response, early or multiply relapse and/or signs of transformation.
      The ideal place for allogeneic transplantation is even harder to define, as the
      curative potential might be outweighed by the substantial side effect profile and
      the indication must always be discussed in the light of available alternatives.
      In consequence, transplantation strategies remain an important therapeutic
      instrument for patients with FL, however timing within the treatment course has
      to be defined individually.

PMID- 29452665
TI  - Novel agents for relapsed and refractory follicular lymphoma.
AB  - Follicular lymphoma is one of the most common non-Hodgkin's lymphomas. Although
      current frontline regimens are associated with high response rates, most patients
      still relapse. When progression is discovered, re-establishing the diagnosis and
      ruling out transformation in paramount. The outcomes following relapse have been
      improving due to the activity and increasing availability of novel agents with
      various mechanisms of action. Despite these advances, single agent activity is
      limited and the disease remains incurable in the majority of cases. Examples of
      drug classes with promising activity in relapsed disease include anti-CD20
      monoclonal antibodies, immunomodulatory drugs (IMiDs), small molecule tyrosine
      kinase inhibitors, bcl2 inhibitors, epigenetic modifiers, conjugated antibodies,
      and checkpoint inhibitors. Many drugs in each class are associated with unique,
      variable and often surprising toxicity profiles. Combination studies are
      currently underway with novel-novel combinations and with traditional
      chemotherapy regimens. This overview will discuss the results of several recent
      studies exploring activity of novel drugs in relapsed follicular lymphoma.

PMID- 29452666
TI  - Transformation of follicular lymphoma - Why does it happen and can it be
      prevented?
AB  - Follicular lymphoma is a clinical disease with a multitude of presentations and
      behaviors. Although infrequent, transformation of follicular lymphoma to a more
      aggressive behaving subtype - prototypically diffuse large B-cell lymphoma -
      confers a substantially adverse prognosis. There is no consensus for optimal
      management after transformation is recognized. Historically considered a distinct
      clinical event, this review highlights the multiple subclinical transformational
      events that either variably or cumulatively result in clinical recognition of
      transformed follicular lymphoma. Known and suspected events include genetic and
      epigenetic perturbations, metabolomic changes, and alterations in the
      microenvironment. This diverse spectrum of pathways leads to heterogeneous
      clinical presentations and outcomes of transformed follicular lymphoma. Current
      options for prevention of transformation are limited to known strategies of
      managing follicular lymphoma before the transformation is recognized. Although
      most retrospectively analyzed studies suggest an association of lower
      transformation rates with early systemic therapy, specific components of therapy
      such as anti-CD20 antibodies, anthracyclines, or purine analogues are less
      strongly associated with "preventative' value. Thus, the goal of preventing
      transformation is of limited value among all factors that go into decisions on
      early management of follicular lymphoma. Future opportunities to prevent clinical
      evidence of transformation will benefit from early detection of markers of
      subclinical transformation and development of therapies to specifically target
      the biology implied by those markers.

PMID- 29452667
TI  - Overview on the management of non-gastric MALT lymphomas.
AB  - Extranodal marginal zone B-cell lymphomas (EMZLs) of the mucosa-associated
      lymphoid tissue (MALT) are indolent lymphomas which can present at any extranodal
      site. The most frequent localizations (other than stomach) are ocular adnexa,
      salivary gland, skin, lung and thyroid. Chronic inflammation and antigenic
      stimulation are a potential risk for the development of MALT lymphomas. While
      Helicobacter Pylori (HP) is known to be associated with gastric MALT lymphoma and
      antibiotic therapy is effective in the setting of HP-positive, other
      microorganisms (such as Chlamydophila Psittaci, Campylobacter Jejiuni, Borrelia
      Burgdoferi) have been implicated in the pathogenesis of non-gastric MALT
      lymphomas. However, antibiotic therapy has not been extensively investigated for
      the non-gastric type, except for ocular adnexal MALT lymphoma, which could
      benefit from an upfront treatment with doxycycline. Surgery, radiotherapy,
      Rituximab alone or in combination with chemotherapy and "chemo-free" approaches,
      including lenalidomide, have shown efficacy in the treatment of non-gastric MALT
      lymphomas.

PMID- 29452668
TI  - Should rituximab replace splenectomy in the management of splenic marginal zone
      lymphoma?
AB  - BACKGROUND: SMZL is a relatively rare low grade B-cell lymphoma, characterized
      usually by an indolent clinical behavior. Since there is no prospective
      randomized trials to establish the best treatment approach, decision on
      therapeutic management should be based on the available retrospective series.
      Based on these data, rituximab and splenectomy appear to be the most effective.
      Splenectomy represented the standard treatment modality until early 2000s. More
      than 90% of the patients present quick amelioration of splenomegaly related
      symptoms along with improvement of cytopenias related to hypersplenism. The
      median progression free survival was 8.25 years in the largest series of patients
      published so far, while the median 5- and 10- year OS were 84% and 67%,
      respectively. Responses to splenectomy are not complete since extrasplenic
      disease persists. Patients with heavy bone marrow infiltration, lymphadenopathy
      or other disease localization besides the spleen are not good candidates for
      splenectomy. Furthermore splenectomy is a major surgical procedure accompanied by
      acute perioperative complications as well as late toxicities mainly due to
      infections. For that reasons splenectomy is not appropriate for elderly patients
      or patients with comorbidities with a high surgical risk. On the other hand
      rituximab monotherapy displays high efficacy with minimal toxicity. Several
      published series have shown an ORR more than 90%, with high CR rates (~50%). The
      10-year PFS and OS were 63% and 85%, respectively in a series of 104 SMZL
      patients. The role of rituximab maintenance has been investigated by only one
      group. Based on these data, maintenance with rituximab further improved the
      quality of responses by increasing significantly the CR rates (from 42% at the
      end of induction to 71% at the end of maintenance treatment), as well as the
      duration of responses: 7-year PFS was 75% for those patients who received
      maintenance vs 39% for those who did not (p < 0.0004). However no difference in
      OS has been noticed between the two groups, so far. Summarizing the above data,
      it is obvious that Rituximab monotherapy is associated with high response rates,
      long response duration and favorable safety profile, rendering it as the
      treatment of choice in SMZL.

PMID- 29452669
TI  - Optimal management of the young patient CLL patient.
AB  - The emergence of targeted therapy for patients with chronic lymphocytic leukemia
      (CLL) has permanently altered the therapeutic landscape. In both upfront and
      relapsed settings, safe and effective oral kinase inhibitors are available which
      rival the responses and durability seen with standard chemo immunotherapy
      regimens. In 2016, ibrutinib was granted Federal Drug Administration approval for
      first-line therapy in patients with CLL. While its role as initial therapy for
      older, unfit or deleted 17p CLL patients is less controversial, its role as first
      line treatment for younger fit patients is less clear, begging the question, what
      is the optimal treatment for these patients, novel agents or standard CIT
      strategies? In this review, we aim to provide guidance for what we believe is the
      optimal management of young fit patients with CLL.

PMID- 29452670
TI  - What is the optimal management of older CLL patients?
AB  - CLL is the most common leukemia in older adults with a median age at diagnosis of
      71. Therefore, management of patients with this disease must take into account
      the older age of most patients and consequences of this in terms of functional
      status and organ function. This review will discuss the management of CLL with
      regards to observation prior to the initiation of therapy, functional status, and
      initial treatment. We will discuss criteria for the initiation of therapy, and
      how initial therapy is different between older and younger patients. Finally, we
      will discuss specific therapies including chemoimmunotherapy and newer targeted
      therapies that are being used widely in the older patient population.

PMID- 29452671
TI  - What is the optimal initial management of the younger mantle cell lymphoma
      patient?
AB  - The last 20 years has seen considerable advances made in the management of
      younger patients with mantle cell lymphoma. The use of high dose cytarabine and
      rituximab in induction therapy, usually followed by autologous stem cell
      transplant consolidation, has become established practice and the median overall
      survival now exceeds 10 years. However, this high intensity upfront approach is
      not necessarily appropriate for all newly diagnosed patients. A minority exhibit
      disease that behaves in an indolent fashion with no proven benefit from early
      intervention, and at the opposite end of the spectrum a high-risk group exists
      who do poorly with conventional treatment. This review considers the role of
      watch and wait strategies in indolent presentations, examines the evidence behind
      current induction approaches and considers ways to modify these for those young
      patients presenting with adverse features. It concludes with an assessment of the
      emerging role of novel agents and the search for robust risk-adapted treatment
      strategies.

PMID- 29452672
TI  - What is the optimal initial management of the older MCL patient?
AB  - The current first line treatment of a patient with mantle cell lymphoma (MCL) is
      often considered as too toxic for elderly patients. The elderly, however,
      comprise the majority of the patients with MCL. The results of several recent
      studies have shown that the outcome of this patient group is not as dismal as in
      the past. Indeed, if patients are not considered frail, and can tolerate
      rituximab and moderate intensive chemotherapy such as R-CHOP followed by
      rituximab maintenance or R-bendamustine, a 4-year overall survival of >80% can be
      achieved. In this chapter the developments of the regimens, resulting in the
      standard treatment options for these patients, are discussed.

PMID- 29452673
TI  - Clearing the haze around medicinal cannabis.

PMID- 29452674
TI  - Pimavanserin for patients with Alzheimer's disease psychosis.

PMID- 29452675
TI  - DBS for Parkinson's disease with behavioural disturbances.

PMID- 29452676
TI  - The future of seizure detection.

PMID- 29452677
TI  - Corrections.

PMID- 29452678
TI  - The advocacy role of the World Federation of Neurology.

PMID- 29452679
TI  - Distinct representation of muscle weakness in QMG and MG-ADL.

PMID- 29452680
TI  - Distinct representation of muscle weakness in QMG and MG-ADL - Authors' reply.

PMID- 29452682
TI  - Brian Andrew Gordon.

PMID- 29452681
TI  - The enthusiasm of Christian Elger.

PMID- 29452683
TI  - Temporal lobe epilepsy in The Passion According to GH.

PMID- 29452684
TI  - Evaluation of the safety, tolerability, and efficacy of pimavanserin versus
      placebo in patients with Alzheimer's disease psychosis: a phase 2, randomised,
      placebo-controlled, double-blind study.
AB  - BACKGROUND: Pimavanserin is a selective 5-HT2A receptor inverse agonist and
      antagonist approved in the USA for the treatment of hallucinations and delusions
      associated with Parkinson's disease psychosis. No safe or effective
      pharmacological treatment is approved for psychosis in patients with Alzheimer's
      disease. Therefore, we aimed to evaluate the safety, tolerability, and efficacy
      of pimavanserin versus placebo in patients with Alzheimer's disease psychosis.
      METHODS: We did a phase 2, randomised, double-blind, placebo-controlled, single
      centre (with multiple affiliated nursing home sites across the UK) study. We
      included participants of either sex who were aged 50 years or older with possible
      or probable Alzheimer's disease and psychotic symptoms including visual or
      auditory hallucinations, delusions, or both. Participants were randomly assigned
      (1:1) to 12 weeks of oral treatment with either pimavanserin (two 17 mg tablets
      daily) or placebo, with use of permuted block sizes of four and stratified by
      baseline Mini-Mental State Examination (MMSE) total score (<6 or >=6) and
      Neuropsychiatric Inventory-Nursing Home version (NPI-NH) psychosis score (<12 or
      >=12). Participants, caregivers, the study sponsor, and study personnel at the
      clinic site were masked to treatment assignment. The primary endpoint was mean
      change from baseline to week 6 in the NPI-NH psychosis score for pimavanserin
      versus placebo in the modified intention-to-treat population. Sustained benefit
      and safety of pimavanserin were assessed through week 12. This study is
      registered at ClinicalTrials.gov, number NCT02035553. FINDINGS: Between Jan 16,
      2014, and Oct 27, 2016, 345 participants across 133 nursing homes were screened,
      of whom 181 were randomly assigned treatment (n=90 pimavanserin and n=91
      placebo). 178 participants were included in the modified intention-to-treat
      population. Mean total baseline NPI-NH psychosis scores were 9.5 (SD 4.8) for the
      pimavanserin group and 10.0 (5.6) for the placebo group. Mean change in the NPI
      NH psychosis score at week 6 was -3.76 points (SE 0.65) for pimavanserin and 
      1.93 points (0.63) for placebo (mean difference -1.84 [95% CI -3.64 to -0.04],
      Cohen's d=-0.32; p=0.045). By week 12, no significant advantage for pimavanserin
      versus placebo was observed for the overall study population (treatment
      difference -0.51 [95% CI -2.23 to 1.21]; p=0.561). Common adverse events were
      falls (21 [23%] of 90 participants in the pimavanserin group vs 21 [23%] of 91 in
      the placebo group), urinary tract infections (20 [22%] vs 25 [28%]), and
      agitation (19 [21%] vs 13 [14%]). Eight (9%) participants on pimavanserin and 11
      (12%) on placebo discontinued treatment because of adverse events. No detrimental
      effect was observed on cognition or motor function in either group.
      INTERPRETATION: Pimavanserin showed efficacy in patients with Alzheimer's disease
      psychosis at the primary endpoint (week 6) with an acceptable tolerability
      profile and without negative effect on cognition. Further follow-up to week 12
      did not show significant advantage for pimavanserin versus placebo. FUNDING:
      ACADIA Pharmaceuticals.

PMID- 29452686
TI  - Technological advances and changing indications for lumbar puncture in
      neurological disorders.
AB  - Technological advances have changed the indications for and the way in which
      lumbar puncture is done. Suspected CNS infection remains the most common
      indication for lumbar puncture, but new molecular techniques have broadened CSF
      analysis indications, such as the determination of neuronal autoantibodies in
      autoimmune encephalitis. New screening techniques have increased sensitvity for
      pathogen detection and can be used to identify pathogens that were previously
      unknown to cause CNS infections. Evidence suggests that potential treatments for
      neurodegenerative diseases, such as Alzheimer's disease, will rely on early
      detection of the disease with the use of CSF biomarkers. In addition to being
      used as a diagnostic tool, lumbar puncture can also be used to administer
      intrathecal treatments as shown by studies of antisense oligonucleotides in
      patients with spinal muscular atrophy. Lumbar puncture is generally a safe
      procedure but complications can occur, ranging from minor (eg, back pain) to
      potentially devastating (eg, cerebral herniation). Evidence that an atraumatic
      needle tip design reduces complications of lumbar puncture is compelling, and
      reinforces the need to change clinical practice.

PMID- 29452687
TI  - Diagnostic challenges in epilepsy: seizure under-reporting and seizure detection.
AB  - Epileptic seizures vary greatly in clinical phenomenology and can markedly affect
      the patient's quality of life. As therapeutic interventions focus on reduction or
      elimination of seizures, the accurate documentation of seizure occurrence is
      essential. However, patient self-evaluation compared with objective evaluation by
      video-electroencephalography (EEG) monitoring or long-term ambulatory EEG
      revealed that patients document fewer than 50% of their seizures, on average, and
      that documentation accuracy varies significantly over time. For good clinical
      practice in epilepsy, novel and feasible seizure detection techniques for
      ambulatory long-term use are needed. Generalised tonic-clonic seizures can
      already be detected reliably by methods that rely on motion recording (eg,
      surface electromyography). However, the automatic detection of other seizure
      types, such as complex partial seizures, will require multimodal approaches that
      combine the measurement of ictal autonomic alterations (eg, heart rate) and of
      characteristic movement patterns (eg, accelerometry). Innovative and feasible
      tools for automatic seizure detection are likely to advance both monitoring of
      the outcome of a treatment in a patient and clinical research in epilepsy.

PMID- 29452685
TI  - Behavioural outcomes of subthalamic stimulation and medical therapy versus
      medical therapy alone for Parkinson's disease with early motor complications
      (EARLYSTIM trial): secondary analysis of an open-label randomised trial.
AB  - BACKGROUND: Although subthalamic stimulation is a recognised treatment for motor
      complications in Parkinson's disease, reports on behavioural outcomes are
      controversial, which represents a major challenge when counselling candidates for
      subthalamic stimulation. We aimed to assess changes in behaviour in patients with
      Parkinson's disease receiving combined treatment with subthalamic stimulation and
      medical therapy over a 2-year follow-up period as compared with the behavioural
      evolution under medical therapy alone. METHODS: We did a parallel, open-label
      study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We
      recruited patients with Parkinson's disease who were disabled by early motor
      complications. Participants were randomly allocated (1:1) to either medical
      therapy alone or bilateral subthalamic stimulation plus medical therapy. The
      primary outcome was mean change in quality of life from baseline to 2 years. A
      secondary analysis was also done to assess behavioural outcomes. We used the
      Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour
      between baseline and 2-year follow-up. Apathy was also measured using the
      Starkstein Apathy Scale, and depression was assessed with the Beck Depression
      Inventory. The secondary analysis was done in all patients recruited. We used a
      generalised estimating equations (GEE) regression model for individual items and
      mixed model regression for subscores of the Ardouin scale and the apathy and
      depression scales. This trial is registered with ClinicalTrials.gov, number
      NCT00354133. The primary analysis has been reported elsewhere; this report
      presents the secondary analysis only. FINDINGS: Between July, 2006, and November,
      2009, 251 participants were recruited, of whom 127 were allocated medical therapy
      alone and 124 were assigned bilateral subthalamic stimulation plus medical
      therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (
      363.3 mg/day [SE 41.8]) in individuals allocated bilateral subthalamic
      stimulation plus medical therapy and was increased by 21% (245.8 mg/day [40.4])
      in those assigned medical therapy alone (p<0.0001). Neuropsychiatric fluctuations
      decreased with bilateral subthalamic stimulation plus medical therapy during 2
      year follow-up (mean change -0.65 points [SE 0.15]) and did not change with
      medical therapy alone (-0.02 points [0.15]); the between-group difference in
      change from baseline was significant (p=0.0028). At 2 years, the Ardouin scale
      subscore for hyperdopaminergic behavioural disorders had decreased with bilateral
      subthalamic stimulation plus medical therapy (mean change -1.26 points [SE 0.35])
      and had increased with medical therapy alone (1.12 points [0.35]); the between
      group difference was significant (p<0.0001). Mean change from baseline at 2 years
      in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the
      Starkstein Apathy Scale score, and the Beck Depression Inventory score did not
      differ between treatment groups. Antidepressants were stopped in 12 patients
      assigned bilateral subthalamic stimulation plus medical therapy versus four
      patients allocated medical therapy alone. Neuroleptics were started in nine
      patients assigned medical therapy alone versus one patient allocated bilateral
      subthalamic stimulation plus medical therapy. During the 2-year follow-up, two
      individuals assigned bilateral subthalamic stimulation plus medical therapy and
      one patient allocated medical therapy alone died by suicide. INTERPRETATION: In a
      large cohort with Parkinson's disease and early motor complications, better
      overall behavioural outcomes were noted with bilateral subthalamic stimulation
      plus medical therapy compared with medical therapy alone. The presence of
      hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged
      additional arguments in favour of subthalamic stimulation if surgery is
      considered for disabling motor complications. FUNDING: German Federal Ministry of
      Education and Research, French Programme Hospitalier de Recherche Clinique
      National, and Medtronic.

PMID- 29452688
TI  - Comparison of the Efficacy and Safety of Orbital and Rotational Atherectomy in
      Calcified Narrowings in Patients Who Underwent Percutaneous Coronary
      Intervention.
AB  - We aimed to compare the safety and efficacy of rotational atherectomy (RA) and
      orbital atherectomy (OA) during percutaneous coronary intervention in an all
      comer population with severely calcified lesions. We included all patients who
      underwent percutaneous coronary intervention with OA or RA in our institution
      from October 2013 until October 2016. Comparison of baseline and procedural
      characteristics, along with acute complication rates and postprocedural cardiac
      enzyme elevation, was performed. There were 191 RA and 57 OA patients. Other than
      creatinine clearance, which was lower in patients with OA (p = 0.01), there were
      no differences in baseline characteristics. OA was more frequent in left anterior
      descending artery lesions (p = 0.02), whereas RA was more common in right
      coronary artery lesions (p = 0.01). Intracoronary imaging rates were above 60% in
      both groups. There was a higher rate of coronary dissections with OA compared
      with RA (p = 0.003), but there was no difference in periprocedural events.
      Maximal troponin levels were similar in both groups. Residual stenosis measured
      by intravascular ultrasound in 29 patients revealed no significant differences
      between OA and RA (p = 0.58). In conclusion, RA and OA have similar safety and
      efficacy profiles in treating patients with calcified coronary lesions, and
      intracoronary imaging is highly beneficial in identifying coronary injury after
      atherectomy procedures.

PMID- 29452689
TI  - Measurements of Lumen Areas and Diameters of Proximal and Middle Coronary Artery
      Segments in Subjects Without Coronary Atherosclerosis.
AB  - There are plenty of data on morphology and lumen dimensions of diseased coronary
      arteries. However, information on normal coronary vessel anatomy is scarce. We
      provided computed tomography angiography-derived reference values of lumen
      dimensions in proximal and middle coronary segments in a healthy population with
      respect to gender and vessel dominance. Consecutive 2,849 computed tomography
      angiography examinations were reviewed to identify 201 subjects (77 men, patient
      age 50 +/- 13 years) whose coronary arteries were free from any sign of
      atherosclerosis (calcium score 0, no detectable plaque). For all proximal and
      middle coronary segments, lumen areas (LAs) and lumen diameters were measured.
      Coronary vessel segmentation and dominance pattern were defined using the Syntax
      Score. Normal values of LAs and lumen diameters were significantly smaller for
      women compared with men except for the proximal right coronary artery and the
      left main coronary artery (LMCA) (20.2 +/- 6.6 mm2 vs 23.0 +/- 6.1 mm2, p =
      0.0003, and 5.0 +/- 0.8 mm vs 5.4 +/- 0.7 mm, p = 0.0001). The lower limit of
      normal for the LMCA (defined as mean LA - 2 standard deviations) equaled 7.0 and
      10.8 mm2 for women and men, respectively. Subjects with left (vs right) coronary
      dominance had significantly larger areas and diameters of the LMCA (26.2 +/- 9.2
      mm2 vs 20.7 +/- 6.0 mm2, p = 0.0017, and 5.7 +/- 1.0 mm vs 5.1 +/- 0.7 mm, p =
      0.0017, respectively) and proximal left circumflex (13.8 +/- 2.7 mm2 vs 10.4 +/-
      3.8 mm2, p = 0.0001, and 4.2 +/- 0.4 mm vs 3.6 +/- 0.7 mm, p = 0.0001,
      respectively) and smaller areas and diameters of the proximal right coronary
      artery (7.1 +/- 2.0 mm2 vs 13.3 +/- 3.6 mm2, p <0.0001, and 3.0 +/- 0.4 mm vs 4.1
      +/- 0.6 mm, p <0.0001, respectively). In conclusion, gender and coronary artery
      dominance pattern significantly impact normal LAs and dimensions in subjects
      without coronary atherosclerosis.

PMID- 29452690
TI  - Utility of Physician Selection of Cardiac Tests in a Chest Pain Unit to Exclude
      Acute Coronary Syndrome Among Patients Without a History of Coronary Artery
      Disease.
AB  - There are few data on the utility of physician selection of cardiac tests,
      including no-test, in a chest pain unit (CPU) to rule out acute coronary syndrome
      in low-risk patients without a history of coronary artery disease. We analyzed
      consecutive low-risk patients admitted to our CPU between 2012 and 2014 and
      determined the proportion of patients selected for testing, the type of initial
      cardiac test selected, and the incidence of major adverse cardiac events (MACEs)
      at 30 days and 6 months. The study group comprised 619 patients: mean age 57
      years (27 to 92), 332 women (54%), and 360 (58%) with multiple cardiac risk
      factors. Cardiac testing included 283 no-test (46%); 179 exercise treadmill
      (29%); 113 myocardial perfusion stress scintigraphy (18%); <10% each for exercise
      stress echocardiography and coronary angiography. Testing was negative in 296
      (88%), nondiagnostic in 30 (9%), and positive in 10 patients (3%). There were no
      MACEs at 30 days in any patients, and at 6 months, MACEs were 5 (1.1%). Length of
      stay was less in no-test than in tested patients (5.4 hours vs 9.8 hours, p
      <0.0001), and there was no difference in incidence of MACE at 6 months in no-test
      vs tested patients (2 MACEs vs 3 MACEs). Physician selection of cardiac tests,
      including no-test, promptly identified patients at low risk of acute coronary
      syndrome who could be safely and rapidly discharged from the CPU. Exclusion of
      cardiac testing shortened length of stay and was not associated with increase in
      MACE at 6 months.

PMID- 29452691
TI  - Recurrent Cardiovascular Events in Survivors of Myocardial Infarction With ST
      Segment Elevation (from the AMI-QUEBEC Study).
AB  - The characteristics and predictors of long-term recurrent ischemic cardiovascular
      events (RICEs) after myocardial infarction with ST-segment elevation (STEMI) have
      not yet been clarified. We aimed to characterize the 10-year incidence, types,
      and predictors of RICE. We obtained 10-year follow-up of STEMI survivors at 17
      Quebec hospitals in Canada (the AMI-QUEBEC Study) in 2003. There were 858
      patients; mean age was 60 years and 73% were male. The majority of patients
      receive reperfusion therapy; 53.3% and 39.2% of patients received primary
      percutaneous coronary intervention (PCI) and fibrinolytic therapy, respectively.
      Seventy-five percent of patients underwent in-hospital PCI (elective, rescue, and
      primary). At 10 years, 42% of patients suffered a RICE, with most RICEs (88%)
      caused by recurrent cardiac ischemia. The risk of RICE was the highest during the
      first year (23.5 per patient-year). At 10 years, the all-cause mortality was
      19.3%, with 1/3 of deaths being RICE-related. Previous cardiovascular event,
      heart failure during the index STEMI hospitalization, discharge prescription of
      calcium blocker increased the risk of RICE by almost twofold. Each point increase
      in TIMI (Thrombolysis In Myocardial Infarction) score augmented the risk of RICE
      by 6%, whereas discharge prescription of dual antiplatelets reduced the risk of
      RICE by 23%. Our findings suggested that survivors of STEMI remain at high long
      term risk of RICE despite high rate of reperfusion therapy and in-hospital PCI.
      Patients with previous cardiovascular event, in-hospital heart failure, and high
      TIMI score were particularly susceptible to RICE. Future studies are needed to
      confirm the impacts of calcium blocker and dual antiplatelets on long-term risk
      of RICE.

PMID- 29452692
TI  - Prognostic Significance of Complex Ventricular Arrhythmias Complicating ST
      Segment Elevation Myocardial Infarction.
AB  - The aim of the study was to assess the clinical significance of complex
      ventricular arrhythmias (VAs) (sustained ventricular tachycardia [sVT] and
      ventricular fibrillation [VF]) in patients with ST-segment elevation myocardial
      infarction (STEMI) depending on timing of arrhythmia. We analyzed 4,363
      consecutive patients with STEMI treated invasively between 2004 and 2014. The
      median follow-up was 69.6 months (range: 0 to 139.8 months). The study population
      was divided into 2 main groups; VA group encompassed 476 patients (10.91%) with
      VAs, whereas 3,887 subjects (89.09%) without VT or VF were included into the
      control group. In VA population, prereperfusion VA (34.24%; n = 163) was the most
      common arrhythmia, whereas reperfusion-induced, early postreperfusion, and late
      postreperfusion VAs were diagnosed in 103 (21.64%), 103 (21.64%), and 107
      (22.48%) patients, respectively. Every type of sVT or VF complicating STEMI
      portended significantly worse in-hospital prognosis, however a late onset
      arrhythmia was associated with the highest (over fivefold) and reperfusion
      induced VA with the lowest (less than threefold) increase in mortality risk
      compared with the control group. On the contrary, long-term mortality was
      significantly increased only in subjects with late postreperfusion and
      prereperfusion VAs compared with VA-free population (43.93% and 36.81%,
      respectively vs 22.58%; p <0.001). Apart from cardiogenic shock on admission,
      late postreperfusion (hazard ratio 3.39) and prereperfusion VAs (hazard ratio
      2.76) were the strongest independent predictors of death in the analyzed
      population. In conclusion, 1 in 10 patients with STEMI treated invasively was
      affected by sVT or VF. The clinical impact of VAs was strongly dependent on
      timing of arrhythmia.

PMID- 29452693
TI  - Performance and Safety of a New Ab Interno Gelatin Stent in Refractory Glaucoma
      at 12 Months.

PMID- 29452694
TI  - Chitinase 3 like 1 (CHI3L1) promotes vasculogenic mimicry formation in cervical
      cancer.
AB  - Vasculogenic mimicry (VM) is an alternative microvascular system which tumour
      cells orchestrate, independent of endothelial cell-mediated angiogenesis. VM
      develops tumour vascular networks that correlate with tumour growth, metastasis,
      and short survival time of patients with a number of cancers. However, little is
      known regarding VM in the vascularisation of cervical cancer. Chitinase 3 like 1
      (CHI3L1) has been previously reported to display the ability to induce
      angiogenesis in cervical cancer. Here, we explored a pathological role of CHI3L1
      in tumour cell-mediated vascularisation. Sixty-six samples of cervical cancer
      were collected to examine CHI3L1 expression and VM formation using
      immunohistochemistry and CD34-periodic acid-Schiff (PAS) dual staining. CHI3L1
      expression was significantly correlated with formation of tumour cell-associated
      vascular channels in the absence of endothelial cells (p=0.031). Interestingly,
      tumour samples lacking VM were positively correlated with non-metastasis
      (p=0.035). Patients with VM positive tumours tended to have decreased overall
      survival (OS) compared to those with VM negative samples (43.9 versus 64.6
      months, p=0.079). In addition, recombinant CHI3L1 enhanced cervical cancer cell
      lines to form tube-like structures, supporting the notion that CHI3L1 mediates VM
      in cervical cancer. Our present data reveal the crucial role of CHI3L1 in the
      formation of VM, which may contribute to tumour aggressiveness. Therefore,
      targeting CHI3L1 may be a valuable strategy for the reduction of cervical cancer
      vascularisation and metastasis.

PMID- 29452695
TI  - The combination of maltose-binding protein and BCG-induced Th1 activation is
      involved in TLR2/9-mediated upregulation of MyD88-TRAF6 and TLR4-mediated
      downregulation of TRIF-TRAF3.
AB  - Our previous study demonstrated that maltose-binding protein (MBP) activated Th1
      through the TLR2-mediated MyD88-dependent pathway and the TLR4-mediated TRIF
      dependent pathway. The combination of MBP and BCG synergistically induced Th1
      activation, and the TLR2/9-mediated MyD88-dependent pathway is involved in this
      process. To further explore this mechanism, we stimulated purified mouse CD4+ T
      cells with MBP and BCG in vitro. The results demonstrated that MBP combined with
      BCG synergistically increased IFN-gamma production and TLR2/4/9 expression,
      suggesting the involvement of TLR2/4/9 in the combination-induced Th1 activation.
      Next, TLRs 2/4/9 were blocked to analyze the effects of TLRs on Th1 activation.
      The results demonstrated that MBP induced a low level of Th1 activation by
      upregulating TLR2-mediated MyD88-TRAF6 and TLR4-mediated TRIF-TRAF3 expression,
      whereas MBP combined with BCG induced synergistic Th1 activation, which was not
      only triggered by strong upregulation of TLR2/9-mediated MyD88-TRAF6 expression
      but also by shifting TLR4-mediated TRIF-TRAF3 into the TRIF-TRAF6 pathway.
      Moreover, we observed that a TLR4 antibody upregulated MyD88 expression and a
      TLR9 inhibitor downregulated TRIF expression, indicating that there was cross
      talk between TLRs 2/4/9 in MBP combined with BCG-induced Th1 activation. Our
      findings may expand the knowledge regarding TLR cross-talk involved in regulating
      the Th1 response.

PMID- 29452696
TI  - Embarrassed and Sorry.

PMID- 29452697
TI  - President's Message.

PMID- 29452698
TI  - Are cleavage anomalies, multinucleation, or specific cell cycle kinetics observed
      with time-lapse imaging predictive of embryo developmental capacity or ploidy?
AB  - OBJECTIVE: To determine whether cleavage anomalies, multinucleation, and specific
      cellular kinetic parameters available from time-lapse imaging are predictive of
      developmental capacity or blastocyst chromosomal status. DESIGN: Retrospective
      analysis of prospectively collected data. SETTING: Single academic center.
      PATIENT(S): A total of 1,478 zygotes from patients with blastocysts biopsied for
      preimplantation genetic screening were cultured in the EmbryoScope.
      INTERVENTION(S): Trophectoderm biopsy. MAIN OUTCOME MEASURE(S): Embryo
      dysmorphisms, developmental kinetics, and euploidy. RESULT(S): Of the 767
      biopsied blastocysts, 41.6% (95% confidence interval [CI], 38%-45%) were
      diagnosed as euploid. Individual dysmorphisms such as multinucleation, reverse
      cleavage, irregular chaotic division, or direct uneven cleavage were not
      associated with aneuploidy. Direct uneven cleavage and irregular chaotic division
      embryos did, however, exhibit lower developmental potential. The presence of two
      or more dysmorphisms was associated with an overall lower euploidy rate, 27.6%
      (95% CI 19%-39%). Early embryo kinetics were predictive of blastocyst development
      but not ploidy status. In contrast, chromosomal status correlated significantly
      with start time of blastulation (tSB), expansion (tEB), and the tEB-tSB interval.
      A lower euploidy rate, 36.6% (95% CI 33%-42%) was observed with tSB >= 96.2
      hours, compared with 48.2% with tSB < 96.2 (95% CI 42%-54%). A drop in euploidy
      rate to 30% (95% CI 25%-37%) was observed in blastocysts with delayed expansion
      (tEB > 116). The proportion of euploid blastocysts was increased with tEB-tSB
      intervals of <=13 hours. A logistic regression model to enhance the probability
      of selecting a euploid blastocyst was constructed. CONCLUSION(S): Morphokinetics
      may aid in selection of euploid embryos from a cohort of day 5/6 blastocysts.

PMID- 29452699
TI  - Hypolipidemic Components from Medicine Food Homology Species Used in China:
      Pharmacological and Health Effects.
AB  - Hyperlipidemia is a systemic disease caused by abnormal human lipid metabolism.
      Dietary control and treatment on hyperlipidemia is now a popular therapy pathway.
      This paper focuses on the medicine food homology (MFH) species used in China with
      hypolipidemic function, and emphasizes on the active ingredients and their
      pharmacological effect. The single herbal and its hypolipidemic active
      ingredients are summarized through reviewing the relevant literatures published
      in the past twenty years. The ingredients are divided into polysaccharides,
      flavonoids, steroidal saponins, quinones, alkaloids and others, of which the
      related researches are described from the aspects of sources, model and method,
      result and mechanisms, respectively. MFH exerts treating hyperlipidemia through
      inhibiting the biosynthesis of endogenous lipids, promoting the catabolism of
      exogenous lipid, restraining lipid absorption, and anti-lipid peroxidation. It is
      concluded that some MFH species with low toxicity and small side effects can used
      to adjust the diet nutrition to prevent the occurrence of hyperlipidemia and
      cardiovascular disease.

PMID- 29452700
TI  - Liver resection for recurrent hepatocellular carcinoma to improve survivability:
      a proposal of indication criteria.
AB  - BACKGROUND: Despite curative resection of hepatocellular carcinoma, patients have
      a high probability of recurrence. We examined indications for liver resection in
      cases of recurrent hepatocellular carcinoma. METHODS: Patients undergoing a
      second liver resection (n=210) or treatment by transcatheter arterial
      chemoembolization (n=184) for recurrent hepatocellular carcinoma of up to 3
      lesions were included. We developed a prediction score based on prognostic
      factors and compared survival according to this prediction score. RESULTS: The
      prediction score was based on 3 independent variables identified by survival
      analysis in 210 patients undergoing a second liver resection and included age >=
      75 years, tumor size >= 3.0 cm, and multiple tumors. Each patient was assigned a
      total score. Median overall survival in patients undergoing a second liver
      resection with scores of 0, 1, and 2/3 were 7.9 years (95% confidence interval,
      5.6-NA), 4.5 years (3.8-6.2), and 2.6 years (2.1-5.3), respectively (P < 0.001).
      Among patients with a score of 0, the survival in patients undergoing liver
      resection was greater than survival in those undergoing transcatheter arterial
      chemoembolization (median 7.9 [95% confidence interval, 5.6-NA] years versus 3.1
      [2.1-3.7] years, P < 0.001), and resection was an independent factor for
      survival. In contrast, survival did not differ in patients with scores 2/3 (2.6
      years [95% confidence interval, 1.9-5.3] versus 2.3 years [1.6-2.8], P = 0.176).
      CONCLUSION: Liver resection is recommended as first-line therapy for recurrent
      hepatocellular carcinoma in patients with a score of 0, while those with score
      2/3 should be considered candidates for transcatheter arterial chemoembolization.

PMID- 29452701
TI  - Corrigendum to "Inhibition of Fgf signaling in short bowel syndrome increases
      weight loss and epithelial proliferation." [surgery volume 161, number 3 (2017)
      694-703].

PMID- 29452702
TI  - The value proposition of simulation-based education.
AB  - Simulation has become an integral part of physician education, and abundant
      evidence confirms that simulation-based education improves learners' skills and
      behaviors and is associated with improved patient outcomes. The resources
      required to implement simulation-based education, however, have led some
      stakeholders to question the overall value proposition of simulation-based
      education. This paper summarizes the information from a special panel on this
      topic and defines research priorities for the field. Future work should focus on
      both outcomes and costs, with robust measurement of resource investments,
      provider performance (in both simulation and real settings), patient outcomes,
      and impact on the health care organization. Increased attention to training
      practicing clinicians and health care teams is also essential. Clarifying the
      value proposition of simulation-based education will require a major national
      effort with funding from multiple sponsors and active engagement of a variety of
      stakeholders.

PMID- 29452703
TI  - Validation of the eighth edition of the American Joint Committee on Cancer
      staging system for ampulla of Vater cancer.
AB  - BACKGROUND: The American Joint Committee on Cancer recently proposed the eighth
      edition of cancer staging system. Validation studies are required to evaluate the
      prognostic stratification of ampulla of Vater cancer patients. METHODS: In the
      study, 369 operatively resected patients with ampullary cancers were grouped
      based on the eighth T (T1a, limited to sphincter of Oddi; T1b, invasion to
      duodenal submucosa; T2, invasion to duodenal proper muscle; T3a, invasion to
      pancreas <=0.5 cm; T3b, invasion to pancreas >0.5 cm; and T4, involvement of
      celiac axis or superior mesenteric artery) and N (N0, no nodal metastasis; N1, 1
      3 nodal metastasis; and N2, >=4 nodal metastasis) category of ampullary cancer
      staging. RESULTS: Overall 5-year survival rates for T and N categories were as
      followed: T1a, 83%; T1b, 71%; T2, 46%; T3a, 48%; T3b, 28.5%, T4, 7% (P< .001);
      N0, 44.8%; N1, 20%; N2, 4% (P < .001). Pair-wise comparisons demonstrated
      significant differences between T1a-b (P = .005), T3a-T3b (P = .03), N0-N1 (P <
      .001), and N1-N2 (P = .007) tumors, but not between T1b-T2 (P = .20), T2-T3a (P =
      .84), and T3b-T4 (P = .17) lesions. CONCLUSION: The eighth edition T category for
      ampullary cancer does not stratify patients accurately with regard to prognosis.
      Modification of the current T category with eliminating subcategories (T1,
      invasion to duodenal submucosa; T2, invasion to duodenal proper muscle; T3,
      invasion to pancreas or duodenal subserosa) is a better way for determining
      prognosis of ampullary cancer. The current N category segregates patient survival
      well.

PMID- 29452704
TI  - Substance Use Disorder Among Current Cancer Patients: Rates and Correlates
      Nationally in the Department of Veterans Affairs.
AB  - BACKGROUND: Substance use disorders (SUDs) are known to cause or complicate
      treatment of many types of cancers. OBJECTIVES: We sought to systematically
      assess rates of current SUDs among patients currently in treatment for cancer.
      METHODS: The National Veteran Health Administration administrative data from
      fiscal year 2012 were used to compare veterans with both cancer and comorbid SUDs
      to veterans with cancer but no SUDs and those with a SUD but no cancer. Bivariate
      comparisons and multivariate logistic regression were used to compare groups on
      sociodemographic characteristics, medical and mental health diagnoses, service
      use, and psychotropic and opioid medication fills. RESULTS: Of 482,688 veterans
      with cancer diagnoses, 32,037 (6.64%) had a comorbid SUD diagnosis. Veterans with
      cancer and a SUD had more medical and psychiatric disorders than those with
      cancer alone, a greater risk of homelessness, and a greater use of both mental
      and medical health services, with 60% receiving mental health outpatient
      treatment. These veterans had fewer differences from veterans with SUDs only,
      although they were older and had more medical illnesses. Notably the cancer SUD
      group had higher rates of hepatic disease and received a greater number of opioid
      prescriptions than both veterans with cancer alone and veterans with SUD alone.
      CONCLUSIONS: Veterans with cancer and SUD showed a specific risk for liver
      disease and a higher use of opioids. Collaborative teams involving oncology,
      palliative care, and psychiatry may be best able to address the challenge of
      providing adequate and safe opiate pain control for this vulnerable population.

PMID- 29452706
TI  - The ever-broadening field of application of transcatheter pulmonary valves.

PMID- 29452707
TI  - Definition of postoperative bleeding in children undergoing cardiac surgery with
      cardiopulmonary bypass: One size doesn't fit all.

PMID- 29452708
TI  - Endovascular treatment of bronchial aneurysms.

PMID- 29452705
TI  - The Changing Incidence and Presentation of Urinary Stones Over 3 Decades.
AB  - OBJECTIVE: To evaluate trends in the incidence of kidney stones and
      characteristics associated with changes in the incidence rate over 3 decades.
      PATIENTS AND METHODS: Adult stone formers in Olmsted County, Minnesota, from
      January 1, 1984, to December 31, 2012, were validated and characterized by age,
      sex, stone composition, and imaging modality. The incidence of kidney stones per
      100,000 person-years was estimated. Characteristics associated with changes in
      the incidence rate over time were assessed using Poisson regression models.
      RESULTS: There were 3224 confirmed symptomatic (stone seen), 606 suspected
      symptomatic (no stone seen), and 617 incidental asymptomatic kidney stone
      formers. The incidence of confirmed symptomatic kidney stones increased from the
      year 1984 to 2012 in both men (145 to 299/100,000 person-years; incidence rate
      ratio per 5 years, 1.14, P<.001) and women (51 to 217/100,000 person-years;
      incidence rate ratio per 5 years, 1.29, P<.001). Overall, the incidence of
      suspected symptomatic kidney stones did not change, but that of asymptomatic
      kidney stones increased. Utilization of computed tomography for confirmed
      symptomatic stones increased from 1.8% in 1984 to 77% in 2012; there was a
      corresponding higher increased incidence of symptomatic small stones (<=3 mm)
      than of larger stones (>3 mm). Confirmed symptomatic kidney stones with
      documented spontaneous passage also increased. The incidence of kidney stones
      with unknown composition increased more than that of stones with known
      composition. CONCLUSION: The incidence of both symptomatic and asymptomatic
      kidney stones has increased dramatically. The increased utilization of computed
      tomography during this period may have improved stone detection and contributed
      to the increased kidney stone incidence.

PMID- 29452709
TI  - Late restored cardiac function after successful resynchronization by right
      posterior accessory pathway ablation in Wolff-Parkinson-White syndrome associated
      dilated cardiomyopathy.

PMID- 29452710
TI  - Re: Nicolas Mottet, Joaquim Bellmunt, Erik Briers, et al. EAU-ESTRO-ESUR-SIOG
      Guidelines on Prostate Cancer. European Association of Urology; 2017.
      http://uroweb.org/guideline/prostate-cancer: How to Assess the Efficacy of
      Medical Castration.

PMID- 29452711
TI  - Primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease
      characterised by intrahepatic or extrahepatic stricturing, or both, with bile
      duct fibrosis. Inflammation and fibrosis of bile ducts and the liver are followed
      by impaired bile formation or flow and progressive liver dysfunction. Patients
      might be asymptomatic at presentation or might have pruritus, fatigue, right
      upper quadrant pain, recurrent cholangitis, or sequelae of portal hypertension.
      The key diagnostic elements are cholestatic liver biochemistry and bile duct
      stricturing on cholangiography. Genetic and environmental factors are important
      in the cause of the disease, with the intestinal microbiome increasingly thought
      to play a pathogenetic role. Approximately 70% of patients have concurrent
      inflammatory bowel disease and patients require colonoscopic screening and
      surveillance. Primary sclerosing cholangitis is associated with increased
      malignancy risk and surveillance strategies for early cholangiocarcinoma
      detection are limited. No single drug has been proven to improve transplant-free
      survival. Liver transplantation is effective for advanced disease but at least
      25% of patients develop recurrent disease in the graft.

PMID- 29452712
TI  - Over-under topsy-turvy - what's the deal with "healthy obesity"?

PMID- 29452713
TI  - Physiochemical characteristics of aerosol particles collected from the Jokhang
      Temple indoors and the implication to human exposure.
AB  - This paper presents a detailed study on the indoor air pollution in the Jokahng
      Temple at Tibet Plateau, and its implication to human health. The mean
      concentrations of PM1.0 and PM2.5 were 435.0 +/- 309.5 and 483.0 +/- 284.9
      MUg/m3, respectively. The PM2.5 concentration exceeded the National Ambient Air
      Quality Standard (75 MUg/m3) by 6.4 times. The size-segregated aerosols displayed
      a bimodal distribution. One peak was observed in the fine mode (0.4-2.1 MUm) and
      the other peak appeared in the coarse mode (2.1-9.0 MUm). The concentration of
      the total size-resolved PM was 794.3 +/- 84.9 MUg/m3. The mass fraction of coarse
      particles shared by 41.1%, apparently higher than that reported at low altitudes,
      probably due to incomplete combustion at Tibet Plateau with hypoxic atmospheric
      environment. The total concentration of polycyclic aromatic hydrocarbons (PAHs)
      was 331.2 +/- 60.3 ng/m3, in which the concentration of benzo(a)pyrene (BaP) was
      18.5 +/- 4.3 ng/m3, over ten times higher than the maximum permissible risk value
      of 1 ng/m3 on account of carcinogenic potency of particulate PAHs through
      inhalation. PAHs exhibited a trimodal distribution, of which two peaks were
      observed in the fine mode and one peak in the coarse mode. With the aromatic
      rings increasing, the peak intensity increased in the fine mode. Na, Ca, Al, Mg
      and K dominated the elemental mass profiles, and metals displayed a bimodal
      distribution with a dominant peak in the coarse range. The total PAH deposition
      flux was 123.6 and 53.1 ng/h for adults and children, respectively. Coarse
      particles contributed most deposition flux in the head region, while fine
      particles contribute most deposition flux in the alveolar region. The increment
      lifetime cancer risk (ILCR) of PAHs ranaged at 10-5-10-4, indicating potential
      cancer risk to human health. The total deposition flux of metals was estimated at
      1.4-13.2 ng/h. With the size increasing, deposition flux increased in the head
      region while decreased in the alveolar region. The highest ILCR of Cr and Ni were
      4.9 * 10-5 and 1.5 * 10-6, respectively, exceeding the permissible risk of 10-6.
      The hazard quotient (HQ) of Fe (10-5-10-4) and Zn (10-6-10-5) were much lower
      than the safe level of 1.0, and thus they were not considered as a health
      concern.

PMID- 29452714
TI  - Genetic diversity and structure of Rhizobium leguminosarum populations associated
      with clover plants are influenced by local environmental variables.
AB  - The identification and conservation of indigenous rhizobia associated with legume
      plants and their application as biofertilizers is becoming an agricultural
      worldwide priority. However, little is known about the genetic diversity and
      phylogeny of rhizobia in Romania. In the present study, the genetic diversity and
      population composition of Rhizobium leguminosarum symbiovar trifolii isolates
      from 12 clover plants populations located across two regions in Romania were
      analyzed. Red clover isolates were phenotypically evaluated and genotyped by
      sequencing 16S rRNA gene, 16S-23S intergenic spacer, three chromosomal genes
      (atpD, glnII and recA) and two plasmid genes (nifH and nodA). Multilocus sequence
      typing (MLST) analysis revealed that red clover plants are nodulated by a wide
      genetic diversity of R. leguminosarum symbiovar trifolii sequence types (STs),
      highly similar to the ones previously found in white clover. Rhizobial genetic
      variation was found mainly within the two clover populations for both chromosomal
      and plasmid types. Many STs appear to be unique for this region and the genetic
      composition of rhizobia differs significantly among the clover populations.
      Furthermore, our results showed that both soil pH and altitude contributed to
      plasmid sequence type composition while differences in chromosomal composition
      were affected by the altitude and were strongly correlated with distance.

PMID- 29452715
TI  - Cyanobacteria inhabiting biological soil crusts of a polar desert: Sor Rondane
      Mountains, Antarctica.
AB  - Molecular and morphological methods were applied to study cyanobacterial
      community composition in biological soil crusts (BSCs) from four areas (two
      nunataks and two ridges) in the Sor Rondane Mountains, Antarctica. The sampling
      sites serve as control areas for open top chambers (OTCs) that were put in place
      in 2010 at the time of sample collection and will be compared with BSC samples
      taken from the OTCs in the future. Cyanobacterial cell biovolume was estimated
      using epifluorescence microscopy, which revealed the dominance of filamentous
      cyanobacteria in all studied sites except the Utsteinen ridge, where unicellular
      cyanobacteria were the most abundant. Cyanobacterial diversity was studied by a
      combination of molecular fingerprinting methods based on the 16S rRNA gene
      (denaturing gradient gel electrophoresis (DGGE) and 454 pyrosequencing) using
      cyanobacteria-specific primers. The number of DGGE sequences obtained per site
      was variable and, therefore, a high-throughput method was subsequently employed
      to improve the diversity coverage. Consistent with previous surveys in
      Antarctica, both methods showed that filamentous cyanobacteria, such as
      Leptolyngbya sp., Phormidium sp. and Microcoleus sp., were dominant in the
      studied sites. In addition, the studied localities differed in substrate type,
      climatic conditions and soil parameters, which probably resulted in differences
      in cyanobacterial community composition. Furthermore, the BSC growing on gneiss
      pebbles had lower cyanobacterial abundances than BSCs associated with granitic
      substrates.

PMID- 29452716
TI  - Dental Pulp Status of Posterior Teeth in Patients with Oral and Oropharyngeal
      Cancer Treated with Radiotherapy: 1-year Follow-up.
AB  - INTRODUCTION: Teeth may react negatively to pulp sensitivity testing in patients
      who have undergone radiotherapy. The aim of the current investigation was to
      evaluate the pulp sensibility of posterior teeth at 4, 6, and 12 months in
      patients who have undergone radiotherapy for oral and oropharyngeal malignancies.
      METHODS: Seventy-nine patients diagnosed with malignant oral and oropharyngeal
      cancer undergoing radiotherapy underwent cold thermal pulp sensitivity testing
      and electric pulp testing of 4 teeth, 1 from each quadrant. The results were
      recorded at 5 different time points (TPs): before radiotherapy (TP1), at the end
      of radiotherapy at 66-70 Gy (TP2), 4 months after the completion of radiotherapy
      (TP3), 6 months after the completion of radiotherapy (TP4), and 12 months after
      the completion of radiotherapy (TP5). RESULTS: All 288 teeth tested positive to
      cold thermal pulp sensitivity testing and electric pulp testing (EPT) at TP1
      (100%). No tooth responded to the cold test (100%) at TP4 and TP5, and
      progressively higher EPT values were noted during the observation period. A
      statistically significant difference existed in the number of positive responses
      between different TPs. CONCLUSIONS: There was a progressive decrease in pulp
      sensibility from TP1 to TP5 in teeth of patients with oral and oropharyngeal
      cancer who underwent radiotherapy (66-70 Gy). No response to cold thermal tests
      was noted at TP4 (6 months) and TP5 (12 months), and teeth responded at
      increasingly higher EPT values from TP1 through TP5. This result was
      statistically significant.

PMID- 29452717
TI  - Evaluation of the mobility of the shoulder and quality of life after perforator
      flaps for recalcitrant axillary hidradenitis.
AB  - BACKGROUND: Hidradenitis suppurativa is a very debilitating disease, treated by
      antibiotics and excision. The reconstruction is usually done by secondary wound
      healing and/or split-thichness skin graft. The aim of this study was to evaluate
      the reconstruction of the axilla with local perforator flaps as a single stage
      surgical treatment. METHODS: This was a monocentric retrospective study conducted
      between November 2013 and June 2015. We included the patients with a severe
      axillary localization of the disease. Between 6 months and 1 year
      postoperatively, we noted length of complete healing, complications, patients
      satisfaction score about the surgery, DASH functional score, maximum abduction
      angle of the arm, and recurrence of the disease. RESULTS: Thirteen patients were
      included, for a total of seventeen affected axillae. We performed seven
      thoracodorsal artery perforator flaps, seven lateral intercostal artery
      perforator flaps and three serratus anterior artery perforator flaps. The mean
      duration of follow-up was 279.1+/-84.1 days (180-365). The average complete
      healing time was 20.5+/-13.5 days (10-60). Six axillae were compounded (35%). The
      average recurrence rate of HS was 0%. The average score in the DASH questionnaire
      was 68.6+/-35.3 points (39-152) and the average maximum abduction angle of the
      arm was 160.6+/-18.5 degrees. The average score on the satisfaction questionnaire
      was 36.5+/-5.6 points (25-43). CONCLUSION: This is a single stage, reliable and
      effective surgical procedure. The results are very encouraging, with a good
      quality of life, a low functional disability and a shorter healing time.

PMID- 29452718
TI  - Health policies for the reduction of obstetric interventions in singleton full
      term births in Catalonia.
AB  - AIM: To explore the effect of hospital's characteristics in the proportion of
      obstetric interventions (OI) performed in singleton fullterm births (SFTB) in
      Catalonia (2010-2014), while incentives were employed to reduce C-sections.
      METHODS: Data about SFTB assisted at 42 public hospitals were extracted from the
      dataset of hospital discharges. Hospitals were classified according to the level
      of complexity, the volume of births attended, and the adoption of a non
      medicalized delivery (NMD) strategy. The annual average change in the percentage
      for OI was calculated based on Poisson regression models. RESULTS: The rate of OI
      (35% of all SFTB) including C-sections (20.6%) remained stable through the
      period. Hospitals attending less complex cases had a lower average of OI, while
      hospitals attending lower volumes had the highest average. Higher levels of
      complexity increased the use of C-sections (+4% yearly) and forceps (+16%). The
      adoption of the NMD strategy decreased the rate of C-sections. CONCLUSIONS: The
      proportion of OI, including C-sections, remained stable in spite of public
      incentives to reduce them. The adoption of the NMD strategy could help in
      decreasing the rate of OI. To reduce the OI rate, new strategies should be
      launched as the development of low-risk pregnancies units, alignment of
      incentives and hospital payment, increased value of incentives and encouragement
      of a cultural shift towards non-medicalized births.

PMID- 29452719
TI  - Syphilitic chorioretinitis: Final outcome without treatment.

PMID- 29452720
TI  - Evaluation of the biological activities of the IL-15 superagonist complex, ALT
      803, following intravenous versus subcutaneous administration in murine models.
AB  - ALT-803 is a fusion protein complex consisting of an interleukin (IL)-15
      superagonist and a dimeric IL-15 receptor alpha sushi domain IgG1 Fc fusion
      protein. When administered to mice, ALT-803 is capable of inducing natural killer
      (NK) and CD8+ T cell proliferation and activation, and effectively promoting
      potent anti-tumor responses. Currently, ALT-803 is in clinical trials for
      treatment of various solid tumors and hematological malignancies. In the initial
      phase of these clinical studies, intravenous (iv) injection was used according to
      the route used in pre-clinical efficacy studies. In order to evaluate the
      possible advantage of subcutaneous (sc) injection versus iv injection, this study
      compared the biological activity of the two treatment regimens of ALT-803 in pre
      clinical in vivo models. The pharmacokinetics, immune stimulation, and anti-tumor
      efficacy of iv and sc injection routes of ALT-803 in C57BL/6 mice were compared.
      The half-life of ALT-803 was 7.5 h for iv versus 7.7 h for sc with the maximal
      detected serum concentration of ALT-803 to be 3926 ng/ml at 0.5 h time-point
      following iv injection versus 495 ng/ml at 16 h post sc injection.
      Biodistribution studies indicated that sc ALT-803, similarly to iv ALT-803 as
      previously reported, has a greater tissue distribution and longer residence time
      in lymphoid tissues compared to recombinant IL-15. Notably, ALT-803 when
      administered either iv or sc induced comparable proliferation and activation of
      CD8+ T and NK cells and resulted in similar reductions of tumor burden. A
      toxicity study of mice receiving multiple injections of ALT-803 for 4 weeks by iv
      or sc routes revealed equivalent immune-related changes. The gradual absorbance
      into the blood stream and lower maximal blood levels of ALT-803 in sc-injected
      mice, along with similar anti-tumor efficacy support the administration of ALT
      803 by sc injection in patients with various malignancies and infectious
      diseases.

PMID- 29452721
TI  - Use of the Gore Tigris Vascular Stent in Advanced Femoropopliteal Peripheral
      Arterial Disease.
AB  - PURPOSE: To prospectively evaluate the safety and efficacy of using the Tigris
      vascular stent (Gore, Flagstaff, Arizona) alone or in combination with the
      Viabahn stent (Gore) for revascularizing femoropopliteal Trans-Atlantic
      Intersociety Consensus (TASC) type B-D lesions with varying degrees of
      calcification. MATERIALS AND METHODS: Patients with Rutherford stage >= 3 and
      TASC type >= B were included in the study. From January 2015 to April 2017, 31
      segments in 31 patients (21 men, ovarall mean age 73.3 +/- 9.2 years) were
      treated. The breakdown by TASC type and Rutherford stage were TASC B (n = 12), C
      (n = 6), and D (n = 13), and Rutherford 3 (n = 28) and 4 (n = 3). The lesions
      were located in the common femoral artery (n = 1), superficial femoral artery
      (SFA; n = 20), distal SFA to P1 (n = 3), popliteal P1 (n = 1), popliteal P1-3 (n
      = 3), popliteal P2-3 (n = 2), and 1 femoropopliteal bypass. There were 18
      occlusions (58.1%) and 13 stenoses (41.9%). The mean diseased segment length was
      15.5 +/- 9.9 cm with 80.6% of moderate/severe calcification. The follow-up
      consisted of color Doppler ultrasound and clinical assessment at 1, 3, 6, 9, 12,
      and 15 months. RESULTS: Technical success was 100%. There were no periprocedural
      or postprocedural complications. The mean stented lesion length was 17.2 +/- 10.5
      cm with a mean follow-up of 13.1 +/- 6.9 months. Primary patency rates at 6, 9,
      12, and 15 months were, respectively, 100% (24/31 patients), 90.5% (21/31
      patients), 88.9% (20/31 patients), and 80% (15/31 patients). The median
      postprocedural Rutherford stage was 1. Three occlusions occurred at 7, 9, and 14
      months, leading to a target lesion revascularization of 9.7% and a secondary
      patency of 100% at 15 months. Logistic analysis results demonstrated that lesion
      length (P = .003) was associated with reocclusion. Amputation-free survival at 15
      months was 100%. Intrastent restenosis was observed in four cases (12.9%) but
      none were associated with worsening of symptoms. No stent fractures were
      observed. CONCLUSIONS: The Tigris stent used alone or in combination with a
      Viabahn stent for femoropopliteal TASC B-D lesions demonstrated acceptable 12
      month primary patency with a low reintervention rate.

PMID- 29452722
TI  - Traumatic Lingual Hematoma Resulting in Bilateral Temporal Mandibular Joint
      Dislocations.
AB  - BACKGROUND: Lingual hematoma (LH) is a relatively uncommon entity seen after both
      medical and traumatic etiologies. Regardless of the cause, the feared
      complication is acute airway obstruction. CASE REPORT: Our case involves a 39
      year-old man who presented to the Emergency Department via emergency medical
      services with an enlarging LH after an unwitnessed fall, suspected to be an
      alcohol withdrawal seizure. The bleeding was likely exacerbated by previously
      undiagnosed thrombocytopenia. Airway stabilization was rapidly established via
      nasotracheal intubation after standard intubation techniques were deemed
      unfeasible. Despite correction of the coagulopathy, the LH continued to expand,
      resulting in bilateral tympanomandibular joint (TMJ) dislocations. To our
      knowledge, this complication has not been previously reported as a complication
      of LH. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite being a
      relatively uncommon condition, LH has the potential to result in life-threatening
      airway obstruction with limited airway options. Prompt airway stabilization
      should be the first priority upon diagnosis. A rapidly evolving LH can limit
      standard orotracheal rapid sequence intubation options, and may require
      alternative airway procedures. Additionally, ongoing lingual swelling after
      airway stabilization has now been shown in our case to result in bilateral TMJ
      dislocations. Concurrent management of reversible coagulopathy may help prevent
      this complication or reduce its severity.

PMID- 29452723
TI  - Q-marker based strategy for CMC research of Chinese medicine: A case study of
      Panax Notoginseng saponins.
AB  - BACKGROUND: To ensure pharmaceutical quality, chemistry, manufacturing and
      control (CMC) research is essential. However, due to the inherent complexity of
      Chinese medicine (CM), CMC study of CM remains a great challenge for academia,
      industry, and regulatory agencies. Recently, quality-marker (Q-marker) was
      proposed to establish quality standards or quality analysis approaches of Chinese
      medicine, which sheds a light on Chinese medicine's CMC study. PURPOSE: Here
      manufacture processes of Panax Notoginseng Saponins (PNS) is taken as a case
      study and the present work is to establish a Q-marker based research strategy for
      CMC of Chinese medicine. STUDY DESIGN: The Q-markers of Panax Notoginseng
      Saponins (PNS) is selected and established by integrating chemical profile with
      pharmacological activities. Then, the key processes of PNS manufacturing are
      identified by material flow analysis. Furthermore, modeling algorithms are
      employed to explore the relationship between Q-markers and critical process
      parameters (CPPs) of the key processes. At last, CPPs of the key processes are
      optimized in order to improving the process efficiency. RESULTS: Among the 97
      identified compounds, Notoginsenoside R1, ginsenoside Rg1, Re, Rb1 and Rd are
      selected as the Q-markers of PNS. Our analysis on PNS manufacturing show the
      extraction process and column chromatography process are the key processes. With
      the CPPs of each process as the inputs and Q-markers' contents as the outputs,
      two process prediction models are built separately for the extraction process and
      column chromatography process of Panax notoginseng, which both possess good
      prediction ability. Based on the efficiency models of extraction process and
      column chromatography process we constructed, the optimal CPPs of both processes
      are calculated. CONCLUSION: Our results show that the Q-markers derived from CMC
      research strategy can be applied to analyze the manufacturing processes of
      Chinese medicine to assure product's quality and promote key processes'
      efficiency simultaneously.

PMID- 29452724
TI  - Mathematical Modelling for Patient Selection in Proton Therapy.
AB  - Proton beam therapy (PBT) is still relatively new in cancer treatment and the
      clinical evidence base is relatively sparse. Mathematical modelling offers
      assistance when selecting patients for PBT and predicting the demand for service.
      Discrete event simulation, normal tissue complication probability, quality
      adjusted life-years and Markov Chain models are all mathematical and statistical
      modelling techniques currently used but none is dominant. As new evidence and
      outcome data become available from PBT, comprehensive models will emerge that are
      less dependent on the specific technologies of radiotherapy planning and
      delivery.

PMID- 29452725
TI  - Base of tongue cancer-is it tongue cancer located at the base of the tongue, or
      is it a type of lingual tonsil cancer? The perspective from a genomic analysis.
AB  - The aim of this study was to determine whether base of tongue (BOT) cancer is
      tongue cancer located at the base of the tongue or lingual tonsil cancer
      originating from tonsil tissue. This was a retrospective study using data from
      The Cancer Genome Atlas (TCGA). The genomic patterns of three primary cancers
      (BOT, oral tongue, and tonsil) were compared to determine their similarities and
      differences. Gene expression data (n=193; 26 BOT, 125 oral tongue, and 42 tonsil
      cases), copy number alteration data (n=142; 19 BOT, 96 oral tongue, and 27 tonsil
      cases), and somatic mutation data (n=187; 25 BOT, 122 oral tongue, and 40 tonsil
      cases) were analyzed using the t-test, heatmap analysis, and OncoPrint,
      respectively. Clinical information for the three tumour groups was included in
      the analyses. When using multiplatform analysis, BOT cancer showed nearly the
      same genomic pattern as tonsil cancer, but not oral tongue cancer. The chi2 test
      and survival analysis revealed that BOT cancer had the same clinical and survival
      patterns as tonsil cancer. In conclusion, BOT cancer showed a genomic pattern
      similar to that of tonsil cancer, but different to that of oral tongue cancer.
      Further prospective studies are warranted before the results of this study can be
      applied in a clinical setting.

PMID- 29452726
TI  - Randomized clinical trial on condylar fractures: 'open or closed'?

PMID- 29452727
TI  - A systematic review and meta-analysis of sleep architecture and chronic traumatic
      brain injury.
AB  - Sleep quality appears to be altered by traumatic brain injury (TBI). However,
      whether persistent post-injury changes in sleep architecture are present is
      unknown and relatively unexplored. We conducted a systematic review and meta
      analysis to assess the extent to which chronic TBI (>6 months since injury) is
      characterized by changes to sleep architecture. We also explored the relationship
      between sleep architecture and TBI severity. In the fourteen included studies,
      sleep was assessed with at least one night of polysomnography in both chronic TBI
      participants and controls. Statistical analyses, performed using Comprehensive
      Meta-Analysis software, revealed that chronic TBI is characterized by relatively
      increased slow wave sleep (SWS). A meta-regression showed moderate-severe TBI is
      associated with elevated SWS, reduced stage 2, and reduced sleep efficiency. In
      contrast, mild TBI was not associated with any significant alteration of sleep
      architecture. The present findings are consistent with the hypothesis that
      increased SWS after moderate-severe TBI reflects post-injury cortical
      reorganization and restructuring. Suggestions for future research are discussed,
      including adoption of common data elements in future studies to facilitate cross
      study comparability, reliability, and replicability, thereby increasing the
      likelihood that meaningful sleep (and other) biomarkers of TBI will be
      identified.

PMID- 29452728
TI  - Effects of advance care planning on confidence in surrogates' ability to make
      healthcare decisions consistent with older adults' wishes: Findings from a
      randomized controlled trial.
AB  - OBJECTIVE: To investigate how confidence in surrogates' ability to make
      consistent decisions in the future change over time, in the context of an ACP
      intervention that did not improve surrogates' ability to predict an older adult's
      hypothetical treatment preferences. METHODS: The study involved 235 older adults
      and surrogates, randomly allocated to an ACP or control intervention. At
      baseline, end of intervention, and six months later, participants were asked how
      confident they were in the surrogate making decisions in the future that would
      match the older adult's wishes. RESULTS: By the end of the intervention,
      confidence had increased among older adults and surrogates involved in ACP (OR =
      3.1 and 5.8 respectively, p < 0.001), while less change occurred among controls.
      Over the following six months, confidence remained stable among older adults but
      decreased among surrogates (OR = 0.5, p = 0.005). CONCLUSION: ACP increases
      confidence in surrogates' ability to make consistent decisions, which may lighten
      the burden of substitute decision making. Efforts to improve substitute decision
      making must continue so that participants' confidence is not based on the
      mistaken assumption that surrogates can make consistent decisions. PRACTICE
      IMPLICATIONS: Professionals involved in ACP should inform participants that
      confidence in the surrogate may increase in the absence of enhanced predictive
      ability.

PMID- 29452729
TI  - Postoperative pneumonia among patients with and without COPD in Spain from 2001
      to 2015.
AB  - BACKGROUND: To describe and compare incidence, characteristics and outcomes of
      postoperative pneumonia among patients with or without COPD. METHODS: We included
      hospitalized patients aged >=40 years whose medical diagnosis included pneumonia
      and ventilator-associated pneumonia in the secondary's diagnosis field and who
      were discharged from Spanish hospitals from 2001 to 2015. Irrespectively of the
      position at the procedures coding list, we retrieved data about the type of
      surgical procedures using the enhanced ICD-9-CM codes. We grouped admissions by
      COPD status. The data were collected from the National Hospital Discharge
      Database. RESULTS: We included 117,665 hospitalizations of patients that
      developed postoperative pneumonia (18.06% of them had COPD). The incidence of
      postoperative pneumonia was significantly higher in COPD patients than in those
      without COPD (IRR 1.93, 95%CI 1.68-2.24). In hospital-mortality (IHM) was
      significantly lower in the first group of patients (29.79% vs 31.43%, p < 0.05).
      Factors independently associated with IHM, among COPD and non-COPD patients, were
      older age, more comorbidities, mechanical ventilation, pleural drainage tube, red
      blood cell transfusion, dialysis and emergency room admission. Time trend
      analysis showed a significant decrease in IHM from 2001 to 2015. COPD was
      associated with lower IHM (OR 0.91, 95%CI 0.88-0.95). CONCLUSIONS: The incidence
      of postoperative pneumonia was higher in COPD patients than in those without this
      disease. However, IHM was lower among COPD patients. IHM decreased over time,
      regardless of the existence or not of COPD.

PMID- 29452730
TI  - External validation of a decision tree early warning score using only laboratory
      data: A retrospective review of prospectively collected data.
AB  - INTRODUCTION: Early warning scores (EWS) have been developed to identify the
      degree of illness severity among acutely ill patients. One system, The Laboratory
      Decision Tree Early Warning Score (LDT-EWS) is wholly laboratory data based.
      Laboratory data was used in the development of a rare computerized method,
      developing a decision tree analysis. This article externally validates LDT-EWS,
      which is obligatory for an EWS before clinical use. METHOD: We conducted a
      retrospective review of prospectively collected data based on a time limited
      sample of all patients admitted through the medical admission unit (MAU) on a
      Danish secondary hospital. All consecutive adult patients admitted from 2 October
      2008 until 19 February 2009, and from 23 February 2010 until 26 May 2010, were
      included. Validation was made by calculating the discriminatory power as area
      under the receiver-operating curve (AUROC) and calibration (precision) as Hosmer
      Lemeshow Goodness of fit test. RESULTS: A total of 5858 patients were admitted
      and 4902 included (83.7%). In-hospital mortality in our final dataset (n=4902)
      was 3.5%. Discriminatory power (95% CI), identifying in-hospital death was 0.809
      (0.777-0.842). Calibration was good with a goodness-of-fit test of X2=5.37 (7
      degrees of freedom), p=0.62. CONCLUSION: LDT-EWS has acceptable ability to
      identify patients at high risk of dying during hospitalization with good
      precision. Further studies performing impact analysis are required before this
      score should be implemented in clinical practice.

PMID- 29452731
TI  - Submersion injuries in the United States: Patients characteristics and predictors
      of mortality and morbidity.
AB  - INTRODUCTION: Drowning leads to 372,000 deaths annually worldwide and to severe
      morbidity secondary to asphyxiation or aspiration. Previous studies described
      submersion injuries mainly in the pediatric population. This study describes
      characteristics of patients presenting with submersion injuries to United States
      emergency departments (EDs) and identifies predictors of poor outcomes (death or
      long term neurologic deficits) after drowning. METHODS: This retrospective cross
      sectional study included ED visits for submersion injuries from the United States
      2013 Nationwide Emergency Department Sample (NEDS) dataset using discharge data
      (CCS diagnosis codes). Descriptive analysis was done for the collected variables
      and was followed by a multivariate regression analysis to identify predictors of
      poor outcomes (mortality and morbidity). RESULTS: A total of 12,529 weighted
      patients presented to EDs for submersion injury in 2013 yielding a rate of 9.29
      per 100,000 ED visits. Patients were more frequently males (65.8%, 95%CI: 64.0
      67.6) and in the 19-65 years age group (41.8%, 95%CI: 40.0-43.6). Poor outcomes
      were present in 11.7% (95%CI: 10.5-13.0) of patients. Significant positive
      predictors of poor outcomes were: male gender (OR = 1.761, 95%CI: 1.247-2.487);
      presence of chronic conditions involving infectious and parasitic disease (OR =
      2.824, 95%CI: 1.155-6.908), the circulatory system (OR = 12.818, 95%CI: 8.953
      18.351), the respiratory system (OR = 1.498, 95%CI: 1.079-2.079) or the digestive
      system (OR = 2.006, 95%CI: 1.106-3.636); associated motor vehicle traffic injury
      (OR = 5.221, 95%CI: 1.563-17.441) and self-payers. CONCLUSION: Submersion remains
      a high impact emergency condition in the United States. Significant predictors of
      poor outcomes were identified. Prevention efforts targeting susceptible
      population are needed to reduce the impact of submersion injuries on different
      communities in the United States.

PMID- 29452732
TI  - Efficacy of pre-hospital rapid sequence intubation in paediatric traumatic brain
      injury: A 9-year observational study.
AB  - INTRODUCTION: Prehospital airway management of the paediatric patient with
      traumatic brain injury (TBI) is controversial. Endotracheal intubation of
      children in the field requires specific skills and has potential benefits but
      also carries potentially serious complications. We aimed to compare mortality and
      functional outcomes after six months between children with TBI who either
      underwent prehospital rapid sequence intubation (RSI) by trained Intensive Care
      paramedics (ICP) or received no intubation. METHODS: We conducted a retrospective
      study of patients aged <=14 years with suspected TBI in Victoria, Australia.
      Patients were either transported via helicopter and received RSI by an ICP (2005
      2013) or via road ambulance and received no intubation (2006-2013). Prehospital
      data was linked to hospital and 6-month follow-up data to assess mortality and
      functional outcome. RESULTS: A total of 106 patients were included in the study
      of which 87 received RSI by paramedics and 19 did not receive intubation.
      Overall, the intubation success rate was 99% (86/87), with a first-pass success
      rate of 93% (81/87). In total, 67% of patients (n = 41) receiving RSI had a
      favourable functional outcome, compared with 54% of non-intubated patients (n =
      7) (p = 0.36). In the 75 children with major trauma, prehospital RSI was
      associated with a significant decrease in length of hospital stay (523 h vs. 1939
      h, p = 0.03). In the 53 children in this subgroup with available six months data
      the difference in favourable functional outcome increased to 66% (n = 31)vs. 17%
      (n = 1) (p = 0.06). DISCUSSION: Prehospital RSI in paediatric patients with TBI
      can safely be performed by highly trained paramedics. Overall, we observed more
      favourable long-term outcomes in patients who received prehospital intubation
      than those who did not, however our study is not powered to detect a significant
      difference. Intubation prior to transport might be beneficial for major trauma
      patients.

PMID- 29452733
TI  - Trajectory of physical activity after hip fracture: An analysis of community
      dwelling individuals from the English Longitudinal Study of Ageing.
AB  - INTRODUCTION: To analyse physical activity participation in a community-dwelling
      people in England with hip fracture the interval prior to fracture, in the
      fracture recovery period, and a minimum of two years post-fracture. MATERIALS AND
      METHODS: 215 individuals were identified from the English Longitudinal Study of
      Ageing cohort (2002-2014) who sustained a hip fracture following a fall and for
      whom data were available on physical activity participation relating to the
      period pre-fracture, within-fracture recovery phase and post-fracture (minimum of
      two years). Physical activity was assessed using the validated ELSA physical
      activity questionnaire. Prevalence of 'low' physical activity participation was
      calculated and multi-level modelling analyses were performed to explore physical
      activity trajectories over the follow-up phase, and whether age, depression,
      gender and frailty were associated with physical activity participation. RESULTS:
      Prevalence of low physical activity participation within two years prior to hip
      fracture was 16.7% (95% Confidence Intervals (CI): 11.6% to 21.8%). This
      increased at the final follow-up phase to 21.3% (95% CI: 15.1% to 27.6%). This
      was not a statistically significant change (P = 0.100). Age (P = 0.005) and
      frailty (P < 0.001) were statistically significant explanatory variables (P =
      0.005) where older age and greater frailty equated to lower physical activity
      participation. Neither gender (P = 0.288) nor depression (P = 0.121) were
      significant explanatory variables. CONCLUSION: Physical activity levels do not
      significantly change between pre-fracture to a minimum of two years post-hip
      fracture for community-dwelling individuals. This contrasts with previous reports
      of reduced mobility post-hip fracture, suggesting that 'physical activity' and
      'mobility' should be considered as separate outcomes in this population.

PMID- 29452734
TI  - Calcar screw position in proximal humerus fracture fixation: Don't miss high!
AB  - INTRODUCTION: In locked plate fixation of proximal humerus fractures, the calcar
      is an important anchor point for screws providing much-needed medial column
      support. Most locking plate implants utilize a fixed-trajectory locking screw to
      achieve this goal. Consequently, adjustments of plate location to account for
      patient-specific anatomy may result in a screw position outside of the calcar. To
      date, little is known about the consequences of "missing" the calcar during plate
      positioning. This study sought to characterize the biomechanics associated with
      proximal and distal placement of locking plates in a two-part fracture model.
      MATERIALS AND METHODS: This experiment was performed twice, first with elderly
      cadaveric specimens and again with osteoporotic sawbones. Two-part fractures were
      simulated and specimens were divided to represent proximal, neutral, and distal
      plate placements. Non-destructive torsional and axial compression tests were
      performed prior to an axial fatigue test and a ramp to failure. Torsional
      stiffness, axial stiffness, humeral head displacement and stiffness during
      fatigue testing, and ultimate load were compared between groups. RESULTS:
      Cadavers: Proximal implant placement led to trends of decreased mechanical
      properties, but there were no significant differences found between groups.
      Sawbones: Distal placement increased torsional stiffness in both directions (p =
      0.003, p = 0.034) and axial stiffness (p = 0.018) when compared to proximal
      placement. Distal placement also increased torsional stiffness in external
      rotation (p = 0.020), increased axial stiffness (p = 0.024), decreased humeral
      head displacement during fatigue testing, and increased stiffness during fatigue
      testing when compared to neutral placement. DISCUSSION: The distal and neutral
      groups had similar mechanical properties in many cadaveric comparisons while the
      proximal group trended towards decreased construct stiffness. RESULTS: from the
      Sawbones model were more definitive and provided further evidence that proximal
      calcar screw placements are undesirable and distal implant placement may provide
      improved construct stability. CONCLUSION: Successful proximal humerus fracture
      reconstruction is inherent upon anatomic fracture reduction coupled with medial
      column support. Results from this experiment suggest that missing the calcar
      proximally is deleterious to fixation strength, while it is safe, and perhaps
      even desirable, to aim slightly distal to the intended target.

PMID- 29452735
TI  - Letter to the Editor.

PMID- 29452736
TI  - Reply to Letter to the Editor.

PMID- 29452737
TI  - Perioperative Glycemic Control in Patients With Diabetes.

PMID- 29452738
TI  - Can Texting Improve Preoperative and Postoperative Communication With Parents?

PMID- 29452739
TI  - Gender Diversity.

PMID- 29452740
TI  - Trends in the Incidence of Sudden Unexpected Infant Death in the Newborn: 1995
      2014.
AB  - OBJECTIVE: To evaluate the epidemiology of sudden unexpected infant death (SUID)
      over a 20-year period in the US, to assess the potential frequency of sudden
      unexpected postnatal collapse in the early days of life, and to determine if SUID
      rates in the neonatal period (0-27 days) have changed in parallel with rates in
      the postneonatal periods, including the percentages attributed to codes that
      include accidental suffocation. STUDY DESIGN: Data from the US Centers for
      Disease Control and Prevention Linked Birth/Infant Death Records for 1995-2014
      were analyzed for the first hour, day, week, and month of life. A comparison of
      neonatal and postneonatal data related to SUID, including accidental suffocation,
      was carried out. RESULTS: Death records for 1995-2014 indicate that, although
      SUID rates in the postneonatal period have declined subsequent to the 1992
      American Academy of Pediatrics sleep position policy change, newborn SUIDs have
      failed to decrease, and the percentage of SUIDs attributed to unsafe sleep
      conditions has increased significantly in both periods; 29.2% of the neonatal
      cases occurred within the first 6 days of life. CONCLUSIONS: The frequency of
      SUIDs during the neonatal period warrants ongoing attention to all circumstances
      contributing to this category of deaths. The development of a standardized
      definition of sudden unexpected postnatal collapse and a national registry of
      these events is recommended. Ongoing research on the effects of early neonatal
      practices on postneonatal SUID should also be encouraged.

PMID- 29452741
TI  - Magic Angle in Cardiac CT: Eliminating Clinically Relevant Metal Artifacts in
      Pacemaker Leads with a Lead-Tip/Gantry Angle of <=70 degrees .
AB  - RATIONALE AND OBJECTIVE: To identify the influence of various parameters for
      reducing artifacts in computed tomography (CT) of commonly used pacemakers or
      implantable cardioverter-defibrillator (ICD) lead tips. MATERIALS AND METHODS:
      This ex vivo phantom study compared two CT techniques (Dual-Energy CT [DECT] vs.
      Dual-Source CT [DSCT]), as well as the influence of incremental alterations of
      current-time product and pacemaker lead-tip angle with respect to the gantry
      plane. Four pacemaker leads and one ICD lead were evaluated. The images were
      assessed visually on a five-point Likert scale (1 = artifact free to 5 = massive
      artifacts). Likert values 1-3 represent clinically relevant, diagnostic image
      quality. RESULTS: 344 of 400 total images were rated with diagnostic image
      quality. The DECT and dual-source DSCT technique each scored 86% diagnostic image
      quality. Statistically, DECT images showed significantly improved image quality
      (P < .05). Concerning the current-time product, no statistically significant
      change was found. Regarding lead-tip positioning, an angle of <=70 degrees 
      yielded 100% diagnostic image quality. Pacemaker and ICD leads were assessed to
      have statistically significant differences. CONCLUSIONS: Surprisingly, the lead
      tip angle of 70 degrees  has been established as the key angle under which
      diagnostic image quality is always ensured, regardless of the imaging technique.
      Thus, we call 70 degrees  the "Magic angle" in CT pacemaker imaging.

PMID- 29452742
TI  - To switch from Botox to Dysport in children with CP, a real world, dose
      conversion, cost-effectiveness study.
AB  - BACKGROUND AND OBJECTIVES: Children with cerebral palsy (CP) are routinely
      treated with botulinum toxin A (BoNT-A). Two non dose-equivalent and differently
      priced products, Botox and Dysport are used. Depending on the conversion one of
      the products is considerably cheaper. However, the dose conversion factors
      studied to date have varied widely and relevant studies have not included
      children. Our objective here was to compare the efficacy and health economics of
      the switch from Botox to Dysport in children with CP when conversion was set to
      1:2. Specifically were these treatments perceived as equivalent in terms of
      efficacy, duration and side-effects and were the drug cost lowered by using
      Dysport. METHODS: This prospective, real-world, cost-effectiveness population
      based observational study included all children with CP, (n = 159) mean age 9.4
      years (SD, 4.3), in the larger Stockholm area who received BoNT-A between
      September 1, 2014, and December 31, 2015. Parents reported the efficacy, duration
      and side-effects of previous treatment while physicians reported doses and goals
      set by children and parents for the present treatment. Drug acquisition costs
      were provided by county administrators. RESULTS: In connection with 341 visits
      caregivers reported comparable effects of similar duration with these products,
      with few, similar and transient side-effects. The drug-cost per treatment was
      4029 SEK for Botox and 2380 SEK in the case of Dysport. CONCLUSION: When Botox
      was replaced by a two-fold higher Unit dose of Dysport (conversion 1:2) parents
      perceived the treatment of their children with CP to be equally effective while
      the cost was 41% lower according to procured prices.

PMID- 29452743
TI  - Medication wasted - Contents and costs of medicines ending up in household
      garbage.
AB  - BACKGROUND: Despite potentially considerable implications for public health, the
      environment and public funds, medicine waste is an under-researched topic. This
      study aims to analyse medicines drawn from household garbage in Vienna (Austria)
      and to assess possible financial implications for public payers. METHODS: Four
      pharmaceutical waste samples collected by the Vienna Municipal Waste Department
      between April 2015 and January 2016 were investigated with regard to their
      content. The value of medicines was assessed at ex-factory, reimbursement and
      pharmacy retail price levels, and the portion of costs attributable to the social
      health insurance was determined. Data were extrapolated for Vienna and Austria.
      RESULTS: The waste sample contained 1089 items, of which 42% were excluded (non
      pharmaceuticals, non-Austrian origin and non-attributable medicines). A total of
      637 items were further analysed. Approximately 18% of these medicines were full
      packs. 36% of the medicines wasted had not yet expired. Nearly two out of three
      medicines wasted were prescription-only medicines. The majority were medicines
      related to the 'alimentary tract and metabolism' (ATC code A), the 'nervous
      system' (ATC code N) and the 'respiratory system' (ATC code R). The medicines
      wasted had a total value of ? 1965, ? 2987 and ? 4207, expressed at ex-factory,
      reimbursement and pharmacy retail price levels, respectively. Extrapolated for
      Vienna, at least ? 37.65 million in terms of expenditure for public payers were
      wasted in household garbage, corresponding to ? 21 per inhabitant. CONCLUSION:
      This study showed that in Vienna some medicines end up partially used or even
      completely unused in household garbage, including prescription-only medicines,
      non-expired medicines and medicines for chronic diseases. While there might be
      different reasons for medicines being wasted, the findings suggest possible
      adherence challenges as one issue to be addressed.

PMID- 29452744
TI  - Emerging concepts in diagnosis and treatment of syncope by pacing.
AB  - Neuroendocrine syncope is a newly proposed term to embody both syncope of reflex
      and adenosine-related etiology. Recent publications on tilt testing have revealed
      the presence of a hypotensive tendency in some patients, even in the face of
      severe cardioinhibition. This new understanding may allow better selection of
      older reflex syncope patients, documented by ECG loop recorder, for successful
      pacing where tilt testing is ideally negative for a good result in terms of few
      syncope recurrences and prompts a less aggressive management policy when
      hypotensive medication is required. Furthermore, plasma adenosine levels not only
      define a new group of patients who have low adenosine and will respond well to
      cardiac pacing but also, by assessing adenosine receptor affinity, offer a
      possible explanation for vasodepression accompanying severe cardioinhibition. The
      question of the timing of loss of consciousness in reflex syncope needs to be
      addressed because, if consciousness is lost before asystole, pacing is likely to
      be ineffective.

PMID- 29452745
TI  - Does Lidocaine Gel Decrease Procedural Pain for Pediatric Urethral
      Catheterization?

PMID- 29452746
TI  - Update: Can Newer Rapid Influenza Tests Rule Out Disease?

PMID- 29452747
TI  - Accuracy of Clinician Practice Compared With Three Head Injury Decision Rules in
      Children: A Prospective Cohort Study.
AB  - STUDY OBJECTIVE: Three clinical decision rules for head injuries in children
      (Pediatric Emergency Care Applied Research Network [PECARN], Canadian Assessment
      of Tomography for Childhood Head Injury [CATCH], and Children's Head Injury
      Algorithm for the Prediction of Important Clinical Events [CHALICE]) have been
      shown to have high performance accuracy. The utility of any of these in a
      particular setting depends on preexisting clinician accuracy. We therefore assess
      the accuracy of clinician practice in detecting clinically important traumatic
      brain injury. METHODS: This was a planned secondary analysis of a prospective
      observational study of children younger than 18 years with head injuries at 10
      Australian and New Zealand centers. In a cohort of children with mild head
      injuries (Glasgow Coma Scale score 13 to 15, presenting in <24 hours) we assessed
      physician accuracy (computed tomography [CT] obtained in emergency departments
      [EDs]) for the standardized outcome of clinically important traumatic brain
      injury and compared this with the accuracy of PECARN, CATCH, and CHALICE.
      RESULTS: Of 20,137 children, 18,913 had a mild head injury. Of these patients,
      1,579 (8.3%) received a CT scan during the ED visit, 160 (0.8%) had clinically
      important traumatic brain injury, and 24 (0.1%) underwent neurosurgery. Clinician
      identification of clinically important traumatic brain injury based on CT
      performed had a sensitivity of 158 of 160, or 98.8% (95% confidence interval [CI]
      95.6% to 99.8%) and a specificity of 17,332 of 18,753, or 92.4% (95% CI 92.0% to
      92.8%). Sensitivity of PECARN for children younger than 2 years was 42 of 42
      (100.0%; 95% CI 91.6% to 100.0%), and for those 2 years and older, it was 117 of
      118 (99.2%; 95% CI 95.4% to 100.0%); for CATCH (high/medium risk), it was 147 of
      160 (91.9%; 95% CI 86.5% to 95.6%); and for CHALICE, 148 of 160 (92.5%; 95% CI
      87.3% to 96.1%). CONCLUSION: In a setting with high clinician accuracy and a low
      CT rate, PECARN, CATCH, or CHALICE clinical decision rules have limited potential
      to increase the accuracy of detecting clinically important traumatic brain injury
      and may increase the CT rate.

PMID- 29452748
TI  - Knockout of human muscle genes revealed by large scale whole-exome studies.
AB  - Large scale whole-exome sequence studies have revealed that a number of
      individuals from different populations have predicted loss-of-function of
      different genes due to nonsense, frameshift, or canonical splice-site mutations.
      Surprisingly, many of these mutations do not apparently show the deleterious
      phenotypic consequences expected from gene knockout. These homozygous null
      mutations, when confirmed, can provide insight into human gene function and
      suggest novel approaches to correct gene dysfunction, as the lack of the expected
      disease phenotype may reflect the existence of modifier genes that reveal
      potential therapeutic targets. Human knockouts complement the information derived
      from mouse knockouts, which are not always good models of human disease. We have
      examined human knockout datasets searching for genes expressed exclusively or
      predominantly in striated muscle. A number of well-known muscle genes was found
      in one or more datasets, including genes coding for sarcomeric myosins,
      components of the sarcomeric cytoskeleton, sarcoplasmic reticulum and plasma
      membrane, and enzymes involved in muscle metabolism. The surprising absence of
      phenotype in some of these human knockouts is critically discussed, focusing on
      the comparison with the corresponding mouse knockouts.

PMID- 29452749
TI  - Children's physical activity levels during organised sports practices.
AB  - OBJECTIVES: This study measured the physical activity levels of children during
      practice sessions of four popular organised sports in Australia. DESIGN: Cross
      sectional observational design. METHODS: Participants comprised children from
      four local organised sports clubs in suburban Adelaide, South Australia. The
      sports examined were Australian Rules Football (AFL), girls' netball, boys'
      soccer and girls' soccer. Each participant wore a waist-mounted GT3X or
      GT3X+Actigraph accelerometer in either one or two of the practice sessions.
      RESULTS: Participants typically spent 40-50% of each sport practice session in
      moderate to vigorous physical activity (MVPA). Participants in the boys' soccer
      teams spent significantly greater time in MVPA (mean=47% of practice time, 95%
      CI=37%, 57%) than participants in the girls' netball teams (mean=40%, 95% CI=30%,
      50%), participants in the girls' soccer teams (mean=38%, 95% CI=28%, 48%) and
      participants in the boys' AFL teams (mean=40%, 95% CI=36%, 44%). The practice
      sessions contributed approximately half of the 60min of MVPA per day recommended
      by physical activity guidelines for children and young people. CONCLUSIONS: The
      results suggested that organised sports provide a supportive environment for
      physical activity accrual; however, one practice session is insufficient for
      children to reach the amount of MVPA recommended in daily physical activity
      guidelines.

PMID- 29452750
TI  - [Consequences of chronic pain in childhood and adolescence].
AB  - OBJECTIVE: Our aim was to examine and map the consequences of chronic pain in
      children and adolescents. METHOD: A scoping review was carried out in the
      international databases (PubMed, SCOPUS, WOS and CINAHL, Cochrane Library) and
      gray literature. We included documents that addressed psychosocial aspects that
      influence chronic pain, published in English between 2010 and 2016. We excluded
      the documents that dealt with pharmacological treatments, chronic pain derived
      from surgical interventions or where there was no access to full text. 34 of the
      716 documents reviewed were included. RESULTS: Studies show that pain is
      associated with high rates of functional disability, sleep disorders and spectrum
      depression-anxiety. Young people experience higher rates of victimization and
      stigmatization, contributing to social isolation, difficulty in meeting academic
      demands and less opportunity to consume illegal substances. With respect to the
      family, chronic pain has been associated with poorer family functioning and
      considerable investment of economic resources. CONCLUSIONS: This Scoping Review
      shows that functional capacity, sleep, personal development, peer support and
      family functioning are interesting lines in published works. However, gaps in
      knowledge are detected in areas such as risk behaviours, the consequences that
      pain can cause in adulthood and gender inequalities.

PMID- 29452751
TI  - Trends in cancer mortality in Spain: the influence of the financial crisis.
AB  - OBJECTIVE: To determine if the onset of the economic crisis in Spain affected
      cancer mortality and mortality trends. METHOD: We conducted a longitudinal
      ecological study based on all cancer-related deaths and on specific types of
      cancer (lung, colon, breast and prostate) in Spain between 2000 and 2013. We
      computed age-standardised mortality rates in men and women, and fit mixed Poisson
      models to analyse the effect of the crisis on cancer mortality and trends
      therein. RESULTS: After the onset of the economic crisis, cancer mortality
      continued to decline, but with a significant slowing of the yearly rate of
      decline (men: RR = 0.987, 95%CI = 0.985-0.990, before the crisis, and RR = 0.993,
      95%CI = 0.991-0.996, afterwards; women: RR = 0.990, 95%CI = 0.988-0.993, before,
      and RR = 1.002, 95%CI = 0.998-1.006, afterwards). In men, lung cancer mortality
      was reduced, continuing the trend observed in the pre-crisis period; the trend in
      colon cancer mortality did not change significantly and continued to increase;
      and the yearly decline in prostate cancer mortality slowed significantly. In
      women, lung cancer mortality continued to increase each year, as before the
      crisis; colon cancer continued to decease; and the previous yearly downward trend
      in breast cancer mortality slowed down following the onset of the crisis.
      CONCLUSIONS: Since the onset of the economic crisis in Spain the rate of decline
      in cancer mortality has slowed significantly, and this situation could be
      exacerbated by the current austerity measures in healthcare.

PMID- 29452752
TI  - Mental health, family roles and employment status inside and outside the
      household in Spain.
AB  - OBJECTIVE: To document the prevalence of poor mental health by gender and social
      class, and to analyze if poor mental health is associated with the family roles
      or the employment status inside and outside the household. METHOD: A cross
      sectional study based on a representative sample of the Spanish population was
      carried out (n = 14,247). Mental health was evaluated using GHQ-12. Employment
      status, marital status, family roles (main breadwinner and the person who mainly
      carries out the household work) and educational level were considered as
      explanatory variables. Multiple logistic regression models stratified by gender
      and social class were fitted and adjusted odds ratios (aOR) were obtained.
      RESULTS: Gender and social class differences in the prevalence of poor mental
      health were observed. Unemployment was associated with higher prevalence. Among
      men the main breadwinner role was related to poor mental health mainly in those
      that belong to manual classes (aOR = 1.2). Among women, mainly among nonmanual
      classes, these problems were associated to marital status: widowed, separated or
      divorced (aOR = 1.9) and to dealing with the household work by themselves (aOR =
      1.9). CONCLUSIONS: In Spain, gender and social class differences in mental health
      still exist. In addition, family roles and working situation, both inside and
      outside the household, could constitute a source of inequalities in mental
      health.

PMID- 29452753
TI  - [Dual approach for atypical atrial flutter ablation after the Mustard procedure].

PMID- 29452754
TI  - Insulinoma: A retrospective study analyzing the differences between benign and
      malignant tumors.
AB  - BACKGROUND/OBJECTIVES: Insulinoma is a rare pancreatic tumor and, usually, a
      benign disease but can be a malignant one and, sometimes, a highly aggressive
      disease. The aim of this study was to determine differences between benign and
      malignant tumors. METHODS: Retrospective study of 103 patients with insulinoma
      treated in a tertiary center. It was analyzed demographic, clinical, laboratory,
      localization and histologic analysis of tumor and follow up data of subjects in
      order to identify differences between individuals benign and malignant disease.
      RESULTS: Almost all patients (87%) had a benign tumor and survival rates of 100%
      following pancreatic tumor surgery. Those with malignant tumors (13%) have a poor
      prognosis, 77% insulinoma-related deaths over a period of 1-300 months after the
      diagnosis with a survival rate of 24% in five years. The following factors are
      associated with an increased risk of malignant disease: duration of symptoms < 24
      months, fasting time for the occurrence of hypoglycemia < 8 h, blood plasma
      insulin concentration >= 28 MUU/mL and C-peptide >= 4.0 ng/mL at the glycemic
      nadir and tumor size >= 2.5 cm. CONCLUSIONS: Our data help to base the literature
      about these tumors, reinforcing that although insulinoma is usually a single
      benign and surgically treated neoplasia, the malignant one is difficult to treat.
      We highlight the data that help predict a malignancy behavior of tumor and
      suggest a long follow up after diagnosis in these cases.

PMID- 29452755
TI  - Machine learning algorithms based on signals from a single wearable inertial
      sensor can detect surface- and age-related differences in walking.
AB  - The aim of this study was to investigate if a machine learning algorithm
      utilizing triaxial accelerometer, gyroscope, and magnetometer data from an
      inertial motion unit (IMU) could detect surface- and age-related differences in
      walking. Seventeen older (71.5 +/- 4.2 years) and eighteen young (27.0 +/- 4.7
      years) healthy adults walked over flat and uneven brick surfaces wearing an
      inertial measurement unit (IMU) over the L5 vertebra. IMU data were binned into
      smaller data segments using 4-s sliding windows with 1-s step lengths. Ninety
      percent of the data were used as training inputs and the remaining ten percent
      were saved for testing. A deep learning network with long short-term memory units
      was used for training (fully supervised), prediction, and implementation. Four
      models were trained using the following inputs: all nine channels from every
      sensor in the IMU (fully trained model), accelerometer signals alone, gyroscope
      signals alone, and magnetometer signals alone. The fully trained models for
      surface and age outperformed all other models (area under the receiver operator
      curve, AUC = 0.97 and 0.96, respectively; p <= .045). The fully trained models
      for surface and age had high accuracy (96.3, 94.7%), precision (96.4, 95.2%),
      recall (96.3, 94.7%), and f1-score (96.3, 94.6%). These results demonstrate that
      processing the signals of a single IMU device with machine-learning algorithms
      enables the detection of surface conditions and age-group status from an
      individual's walking behavior which, with further learning, may be utilized to
      facilitate identifying and intervening on fall risk.

PMID- 29452756
TI  - Quantification of thrombus formation in malapposed coronary stents deployed in
      vitro through imaging analysis.
AB  - Stent thrombosis is a major complication of coronary stent and scaffold
      intervention. While often unanticipated and lethal, its incidence is low making
      mechanistic examination difficult through clinical investigation alone. Thus,
      throughout the technological advancement of these devices, experimental models
      have been indispensable in furthering our understanding of device safety and
      efficacy. As we refine model systems to gain deeper insight into adverse events,
      it is equally important that we continue to refine our measurement methods. We
      used digital signal processing in an established flow loop model to investigate
      local flow effects due to geometric stent features and ultimately its
      relationship to thrombus formation. A new metric of clot distribution on each
      microCT slice termed normalized clot ratio was defined to quantify this
      distribution. Three under expanded coronary bare-metal stents were run in a flow
      loop model to induce clotting. Samples were then scanned in a MicroCT machine and
      digital signal processing methods applied to analyze geometric stent conformation
      and spatial clot formation. Results indicated that geometric stent features play
      a significant role in clotting patterns, specifically at a frequency of 0.6225 Hz
      corresponding to a geometric distance of 1.606 mm. The magnitude-squared
      coherence between geometric features and clot distribution was greater than 0.4
      in all samples. In stents with poor wall apposition, ranging from 0.27 mm to 0.64
      mm maximum malapposition (model of real-world heterogeneity), clots were found to
      have formed in between stent struts rather than directly adjacent to struts. This
      early work shows how the combination of tools in the areas of image processing
      and signal analysis can advance the resolution at which we are able to define
      thrombotic mechanisms in in vitro models, and ultimately, gain further insight
      into clinical performance.

PMID- 29452757
TI  - Exploring novel objective functions for simulating muscle coactivation in the
      neck.
AB  - Musculoskeletal modeling allows for analysis of individual muscles in various
      situations. However, current techniques to realistically simulate muscle response
      when significant amounts of intentional coactivation is required are inadequate.
      This would include stiffening the neck or spine through muscle coactivation in
      preparation for perturbations or impacts. Muscle coactivation has been modeled
      previously in the neck and spine using optimization techniques that seek to
      maximize the joint stiffness by maximizing total muscle activation or muscle
      force. These approaches have not sought to replicate human response, but rather
      to explore the possible effects of active muscle. Coactivation remains a
      challenging feature to include in musculoskeletal models, and may be improved by
      extracting optimization objective functions from experimental data. However, the
      components of such an objective function must be known before fitting to
      experimental data. This study explores the effect of components in several
      objective functions, in order to recommend components to be used for fitting to
      experimental data. Four novel approaches to modeling coactivation through
      optimization techniques are presented, two of which produce greater levels of
      stiffness than previous techniques. Simulations were performed using OpenSim and
      MATLAB cooperatively. Results show that maximizing the moment generated by a
      particular muscle appears analogous to maximizing joint stiffness. The approach
      of optimizing for maximum moment generated by individual muscles may be a good
      candidate for developing objective functions that accurately simulate muscle
      coactivation in complex joints. This new approach will be the focus of future
      studies with human subjects.

PMID- 29452758
TI  - Supplementation with omega-3 fatty acids and plasma adiponectin in women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To study plasma adiponectin levels in women diagnosed with polycystic
      ovary syndrome given omega-3 fatty acid supplements. PATIENTS AND METHODS: A
      study was conducted in 195 women diagnosed with polycystic ovary syndrome treated
      with omega-3 fatty acids for 12weeks (n=97; groupA) and control women given
      placebo (n=98, groupB). General characteristics, metabolism, lipid profile, and
      hormone and adiponectin levels were compared. RESULTS: There were no significant
      differences between the two groups in general characteristics. No significant
      differences were also found in hormone, blood glucose, and HOMA levels between
      the groups. Women in study groupsA andB showed no statistically significant
      differences in total calorie, carbohydrate, protein, and total fat intake between
      the baseline and final values. Decreased total cholesterol, low-density
      lipoprotein, and triglyceride levels were found in groupA women (P<.0001). Mean
      of adiponectin levels also showed a statistically significant increase after
      treatment (P<.0001). There were no statistically significant differences in the
      mean values of the different variables in groupB women. CONCLUSION: Omega-3 fatty
      acid supplementation for 12weeks caused a significant increase in plasma
      adiponectin levels in women with polycystic ovary syndrome.

PMID- 29452759
TI  - Feasibility Study of Weekly Nanoparticle Albumin-Bound Paclitaxel (150 mg/m2)
      Followed by Fluorouracil, Epirubicin, and Cyclophosphamide Therapy as Neoadjuvant
      Chemotherapy for HER2-Negative Breast Cancer.
AB  - BACKGROUND: Although several studies have shown efficacy of nanoparticle albumin
      bound (nab) paclitaxel use as a neoadjuvant treatment in breast cancer, dosage
      and schedules were varied or used in combination and the data are still limited
      for weekly regimens. We evaluated the feasibility of weekly nab-paclitaxel
      followed by FEC (5-FU [fluorouracil], epirubicin, and cyclophosphamide) treatment
      feasibility as neoadjuvant chemotherapy for breast cancer. PATIENTS AND METHODS:
      Thirty-three patients with no previous chemotherapy were enrolled to receive nab
      paclitaxel 150 mg/m2 the first 3 of 4 weeks (3q4w) followed by FEC as neoadjuvant
      treatment. The trial was powered for analyses of feasibility. RESULTS: Twenty
      five patients completed the treatment as per protocol, and the completion rate
      was 75.8% (95% confidence interval, 59.0-87.2; P = .44). The regimen completion
      group was younger than those with regimen incompletion (average 45.1 vs. 56.6
      years). The pathological complete response (ypT0-is/N0) rate was 30.3% in 33
      patients, which was higher in triple-negative patients (58.3%). Grade 3/4
      neutropenia was seen in 48.5%, although there was no febrile neutropenia. Grade 3
      peripheral neuropathy was seen in 33.3%. CONCLUSION: Our study showed that weekly
      nab-paclitaxel 150 mg/m2 3q4w followed by FEC as neoadjuvant regimen might be
      sufficient in efficacy, although with a relatively high severe adverse event
      occurrence rate.

PMID- 29452760
TI  - Reliable procedure of polyglycolic acid sheet delivery and placement on gastric
      artificial floor: Application of wafer paper and thread.

PMID- 29452761
TI  - Combination therapy could end the recurrence of biliary pancreatitis: It is about
      time!

PMID- 29452762
TI  - A huge rapidly-enlarging multicystic biliary hamartoma.

PMID- 29452763
TI  - The predictive role of E/e' on ischemic stroke and atrial fibrillation in
      Japanese patients without atrial fibrillation.
AB  - BACKGROUND: The predictive role of E/e' on ischemic stroke (IS) and atrial
      fibrillation (AF) in Japanese patients without AF are unclear. METHODS AND
      RESULTS: Shinken database includes all the new patients visiting the
      Cardiovascular Institute Hospital in Tokyo, Japan. E/e' has been routinely
      measured since 2007. Patients without AF for whom E/e' was measured at the
      initial visit between 2007 and 2014 (n=11 477, mean age 57.2 years old, men
      59.5%) were divided into E/e' tertiles (<8.04, 8.04-11.00, >11.00). During the
      mean follow-up period of 1.8 years, 58 IS and 140 new appearances of AF were
      observed. High E/e' tertile was associated with more prevalence of
      atherothrombotic risks. The cumulative incidence of IS events and new appearance
      of AF at 6 years in low, middle, and high E/e' tertiles were 0.5%, 1.4%, and
      3.0%/year (log-rank test, p<0.001), and 2.5%, 2.9%, and 4.2%/year (log-rank test,
      p=0.007), respectively. In multivariate analysis, high E/e' tertile was
      independently associated with IS (HR, 2.857, 95%CI 1.257-6.495, p=0.012).
      Although high E/e' tertile was independently associated with new appearance of AF
      when adjusted for coexistence of atherothrombotic risk factors (HR, 1.694, 95%CI,
      1.097-2.616, p=0.017), the association was attenuated after adjustment for left
      atrial dimension. CONCLUSIONS: E/e' was significantly associated with incidence
      of IS and new appearance of AF in non-AF patients.

PMID- 29452764
TI  - The paradox of increased risk of atrial fibrillation following bariatric surgery.

PMID- 29452765
TI  - Strict sequential catheter ablation strategy targeting the pulmonary veins and
      superior vena cava for persistent atrial fibrillation.
AB  - BACKGROUND: An effective catheter ablation strategy, beyond pulmonary vein
      isolation (PVI), for persistent atrial fibrillation (AF) is necessary. Pulmonary
      vein (PV)-reconduction also causes recurrent atrial tachyarrhythmias. The effect
      of the PVI and additional effect of a superior vena cava (SVC) isolation (SVCI)
      was strictly evaluated. METHODS: Seventy consecutive patients with persistent AF
      who underwent a strict sequential ablation strategy targeting the PVs and SVC
      were included in this study. The initial ablation strategy was a circumferential
      PVI. A segmental SVCI was only applied as a repeat procedure when patients
      demonstrated no PV-reconduction. RESULTS: After the initial procedure, persistent
      AF was suppressed in 39 of 70 (55.7%) patients during a median follow-up of 32
      months. After multiple procedures, persistent AF was suppressed in 46 (65.7%) and
      52 (74.3%) patients after receiving the PVI alone and PVI plus SVCI strategies,
      respectively. In 6 of 15 (40.0%) patients with persistent AF resistant to PVI,
      persistent AF was suppressed. The persistent AF duration independently predicted
      persistent AF recurrences after multiple PVI alone procedures [HR: 1.012 (95%
      confidence interval: 1.006-1.018); p<0.001] and PVI plus SVCI strategies [HR:
      1.018 (95% confidence interval: 1.011-1.025); p<0.001]. A receiver-operating
      characteristic analysis for recurrent persistent AF indicated an optimal cut-off
      value of 20 and 32 months for the persistent AF duration using the PVI alone and
      PVI plus SVCI strategies, respectively. CONCLUSIONS: The outcomes of the PVI plus
      SVCI strategy were favorable for patients with shorter persistent AF durations.
      The initial SVCI had the additional effect of maintaining sinus rhythm in some
      patients with persistent AF resistant to PVI.

PMID- 29452767
TI  - Uptake and distribution of organo-iodine in deep-sea corals.
AB  - Understanding iodine concentration, transport, and bioavailability is essential
      in evaluating iodine's impact to the environment and its effectiveness as an
      environmental biogeotracer. While iodine and its radionuclides have proven to be
      important tracers in geologic and biologic studies, little is known about
      transport of this element to the deep sea and subsequent uptake in deep-sea coral
      habitats. Results presented here on deep-sea black coral iodine speciation and
      iodine isotope variability provides key information on iodine behavior in natural
      and anthropogenic environments, and its geochemical pathway in the Gulf of
      Mexico. Organo-iodine is the dominant iodine species in the black corals,
      demonstrating that binding of iodine to organic matter plays an important role in
      the transport and transfer of iodine to the deep-sea corals. The identification
      of growth bands captured in high-resolution scanning electron images (SEM) with
      synchronous peaks in iodine variability suggest that riverine delivery of
      terrestrial-derived organo-iodine is the most plausible explanation to account
      for annual periodicity in the deep-sea coral geochemistry. Whereas previous
      studies have suggested the presence of annual growth rings in deep-sea corals,
      this present study provides a mechanism to explain the formation of annual growth
      bands. Furthermore, deep-sea coral ages based on iodine peak counts agree well
      with those ages derived from radiocarbon (14C) measurements. These results hold
      promise for developing chronologies independent of 14C dating, which is an
      essential component in constraining reservoir ages and using radiocarbon as a
      tracer of ocean circulation. Furthermore, the presence of enriched 129I/127I
      ratios during the most recent period of skeleton growth is linked to nuclear
      weapons testing during the 1960s. The sensitivity of the coral skeleton to record
      changes in surface water 129I composition provides further evidence that iodine
      composition and isotope variability captured in proteinaceous deep-sea corals is
      a promising geochronometer as well as an emerging tracer for continental material
      flux.

PMID- 29452766
TI  - Traumatic stress and accelerated DNA methylation age: A meta-analysis.
AB  - BACKGROUND: Recent studies examining the association between posttraumatic stress
      disorder (PTSD) and accelerated aging, as defined by DNA methylation-based
      estimates of cellular age that exceed chronological age, have yielded mixed
      results. METHODS: We conducted a meta-analysis of trauma exposure and PTSD
      diagnosis and symptom severity in association with accelerated DNA methylation
      age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium
      PTSD Epigenetics Workgroup (combined N = 2186). Associations between demographic
      and cellular variables and accelerated DNA methylation age were also examined, as
      was the moderating influence of demographic variables. RESULTS: Meta-analysis of
      regression coefficients from contributing cohorts revealed that childhood trauma
      exposure (when measured with the Childhood Trauma Questionnaire) and lifetime
      PTSD severity evidenced significant, albeit small, meta-analytic associations
      with accelerated DNA methylation age (ps = 0.028 and 0.016, respectively). Sex,
      CD4T cell proportions, and natural killer cell proportions were also
      significantly associated with accelerated DNA methylation age (all ps < 0.02).
      PTSD diagnosis and lifetime trauma exposure were not associated with advanced DNA
      methylation age. There was no evidence of moderation of the trauma or PTSD
      variables by demographic factors. CONCLUSIONS: Results suggest that traumatic
      stress is associated with advanced epigenetic age and raise the possibility that
      cells integral to immune system maintenance and responsivity play a role in this.
      This study highlights the need for additional research into the biological
      mechanisms linking traumatic stress to accelerated DNA methylation age and the
      importance of furthering our understanding of the neurobiological and health
      consequences of PTSD.

PMID- 29452769
TI  - The Radiation Resistance of Human Multipotent Mesenchymal Stromal Cells Is
      Independent of Their Tissue of Origin.
AB  - PURPOSE: Human mesenchymal stromal cells (MSCs) may aid the regeneration of
      ionizing radiation (IR)-induced tissue damage. They can be harvested from
      different tissues for clinical purposes; however, the role of the tissue source
      on the radiation response of human MSCs remains unknown. METHODS AND MATERIALS:
      Human MSCs were isolated from adipose tissue, bone marrow, and umbilical cord,
      and cellular survival, proliferation, and apoptosis were measured after
      irradiation. The influence of IR on the defining functions of MSCs was assessed,
      and cell morphology, surface marker expression, and the differentiation potential
      were examined. Western blot analyses were performed to assess the activation of
      DNA damage signaling and repair pathways. RESULTS: MSCs from adipose tissue, bone
      marrow, and umbilical cord exhibited a relative radioresistance independent of
      their tissue of origin. Defining properties including cellular adhesion and
      surface marker expression were preserved, and irradiated MSCs maintained their
      potential for multilineage differentiation irrespective of their tissue source.
      Analysis of activated DNA damage recognition and repair pathways demonstrated an
      efficient repair of IR-induced DNA double-strand breaks in MSCs from different
      tissues, thereby influencing the induction of apoptosis. CONCLUSIONS: These data
      show for the first time that MSCs are resistant to IR and largely preserve their
      defining functions after irradiation irrespective of their tissue of origin.
      Efficient repair of IR-induced DNA double-strand breaks and consecutive reduction
      of apoptosis induction may contribute to the tissue-independent radiation
      resistance of MSCs.

PMID- 29452768
TI  - Qualitative study of challenges of caring for a person with heart failure.
AB  - Heart failure (HF) is a chronic health condition that causes significant
      morbidity among older adults, many of whom receive support and care from an
      informal caregiver. Caregiving is a difficult role with many responsibilities and
      challenges. An in-depth understanding of these challenges is necessary to develop
      services, resources, and interventions for HF caregivers. The goal of this study
      was to qualitatively ascertain the most significant challenges facing HF
      caregivers. We conducted semi-structured interviews with 16 caregivers of a
      person with HF (PHF). Content analysis revealed challenges rooted within the PHF
      (negative affect, resistant behavior, independence, and illness) Caregiver
      (balancing employment, lack of support, time, and caregiver health) and
      Relational level (PHF/caregiver dyadic relationship and other relationships).
      These findings can be used to inform interventions and support services for HF
      caregivers.

PMID- 29452770
TI  - Single-Arm Phase 2 Trial of Elective Nodal Dose Reduction for Patients With
      Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck.
AB  - PURPOSE: To evaluate a novel chemoradiation therapy (CRT) regimen for patients
      with squamous cell carcinoma of the head and neck (SCCHN) incorporating a lower
      intensity modulated radiation therapy dose to electively treated neck lymph nodes
      than is currently standard. METHODS AND MATERIALS: Eligible patients had locally
      advanced SCCHN of the oral cavity, oropharynx, larynx, or hypopharynx. The 7-week
      CRT course consisted of weekly cisplatin at 35 mg/m2 concurrently with sequential
      boost intensity modulated radiation therapy: 36 Gy to high- and low-risk planning
      target volumes followed by a sequential boost to the high-risk planning target
      volume to 70 Gy. The primary endpoint was elective nodal failure. Secondary
      endpoints were survival, toxicity, feeding tube duration, and quality of life
      evaluated by the FACT-HN and QOL-RTI surveys. RESULTS: Between 2011 and 2014, 54
      patients were enrolled, 31 (57%) of whom had human papillomavirus (HPV)-positive
      disease. Of the patients, 35 (65%) had stage IVa disease. The median follow-up
      period for survivors was 36 months (range, 12-66 months). Elective nodal failure
      did not develop in any patient. The actuarial 3-year survival rate for the entire
      cohort was 91% (95% confidence interval [CI] 0.79-0.96); for the HPV-negative
      group, 85% (95% CI 0.61-0.95); and for the HPV-positive group, 96% (95% CI 0.77
      0.99). Common grade 3 toxicities were dysphagia (79%), mucositis and/or
      stomatitis (41%), nausea (20%), xerostomia (13%), vomiting (11%), and neutropenia
      (10%). The median feeding tube duration was 142 days. Patient FACT-HN scores were
      higher at 3, 6, and 12 months versus at the end of treatment (P < .0001). Total
      FACT-HN scores returned to pretreatment baseline by 6 months. Overall QOL-RTI
      scores were lower from pretreatment to the end of treatment through 12 months (P
      = .0001). CONCLUSIONS: This CRT regimen for patients with advanced SCCHN
      demonstrated the potential feasibility of reducing the elective dose to the neck,
      a topic that requires additional study in future clinical trials.

PMID- 29452771
TI  - Radiation Therapy as an Effective Salvage Strategy for Secondary CNS Lymphoma.
AB  - PURPOSE: We assessed the efficacy of radiation therapy (RT) in the management of
      secondary central nervous system (CNS) lymphoma. METHODS AND MATERIALS: The
      cohort comprised 44 patients with systemic diffuse large B-cell lymphoma (DLBCL)
      secondarily involving the brain and/or leptomeninges at initial diagnosis or
      relapse that was treated with RT. RESULTS: Of these patients, 29 (66%) were in
      systemic remission when CNS disease was diagnosed. The overall response rate to
      RT by magnetic resonance imaging was 88% (42% complete, 46% partial). The median
      overall survival (OS) after RT initiation was 7 months (95% confidence interval 4
      10 months). The OS curve plateaued at 31% from 2 to 8 years. OS was superior in
      patients who achieved a complete or partial response to RT, underwent stem cell
      transplantation after RT, and had brain parenchymal (vs leptomeningeal) disease.
      Eight cases of CNS disease progression occurred after RT: 1 involved the brain
      parenchyma, and 7 involved the spine and/or cerebrospinal fluid and/or meninges.
      CONCLUSIONS: We conclude that RT is associated with high response rates and may
      contribute to long-term OS. In addition, RT may provide CNS disease control that
      facilitates successful salvage with stem cell transplantation in patients with
      chemotherapy-refractory disease.

PMID- 29452772
TI  - Metabolic and Lipidomic Reprogramming in Renal Cell Carcinoma Subtypes Reflects
      Regions of Tumor Origin.
AB  - BACKGROUND: Renal cell carcinoma (RCC) consists of prognostic distinct subtypes
      derived from different cells of origin (eg, clear cell RCC [ccRCC], papillary RCC
      [papRCC], and chromophobe RCC [chRCC]). ccRCC is characterized by lipid
      accumulation and metabolic alterations, whereas data on metabolic alterations in
      non-ccRCC are limited. OBJECTIVE: We assessed metabolic alterations and the lipid
      composition of RCC subtypes and ccRCC-derived metastases. Moreover, we elucidated
      the potential of metabolites/lipids for subtype classification and identification
      of therapeutic targets. DESIGN, SETTING, AND PARTICIPANTS: Metabolomic/lipidomic
      profiles were quantified in ccRCC (n=58), chRCC (n=19), papRCC (n=14),
      corresponding nontumor tissues, and metastases (n=9) through a targeted
      metabolomic approach. Transcriptome profiling was performed in corresponding
      samples and compared with expression data of The Cancer Genome Atlas cohorts
      (patients with ccRCC, n=452; patients with papRCC, n=260; and patients with
      chRCC, n=59). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In addition to
      cluster analyses, metabolomic/transcriptomic data were analyzed to evaluate
      metabolic differences of ccRCC and chRCC using Welch's t test or paired t test as
      appropriate. Where indicated, p values were adjusted for multiple testing using
      Bonferroni or Benjamini-Hochberg correction. RESULTS AND LIMITATIONS: Based on
      their metabolic profiles, RCC subtypes clustered into two groups separating ccRCC
      and papRCC from chRCC, which mainly reflected the different cells of origin.
      ccRCC-derived metastases clustered with primary ccRCCs. In addition to
      differences in certain lipids (lysophosphatidylcholines and sphingomyelins), the
      coregulation network of lipids differed between ccRCC and chRCC. Consideration of
      metabolic gene expression indicated, for example, alterations of the polyamine
      pathway at metabolite and transcript levels. In vitro treatment of RCC cells with
      the ornithine-decarboxylase inhibitor difluoromethylornithine resulted in reduced
      cell viability and mitochondrial activity. Further evaluation of clinical utility
      was limited by the retrospective study design and cohort size. CONCLUSIONS: In
      summary, we provide novel insight into the metabolic profiles of ccRCC and non
      ccRCC, thereby confirming the different ontogeny of RCC subtypes. Quantification
      of differentially regulated metabolites/lipids improves classification of RCC
      with an impact on the identification of novel therapeutic targets. PATIENT
      SUMMARY: Several subtypes of renal cell carcinoma (RCC) with different metastatic
      potentials and prognoses exist. In the present study, we provide novel insight
      into the metabolism of these different subtypes, which improves classification of
      subtypes and helps identify novel targets for RCC therapy.

PMID- 29452773
TI  - Corrigendum to "Slow and steady, not fast and furious: Slow temporal modulation
      strengthens continuous flash suppression" [Conscious Cogn. 58 (2018) 10-19].

PMID- 29452774
TI  - Dietary zinc intake and whole blood zinc concentration in subjects with type 2
      diabetes versus healthy subjects: A systematic review, meta-analysis and meta
      regression.
AB  - The aim of this systematic review, meta-analysis and meta-regression was to
      examine the relationship between type 2 diabetes mellitus (T2DM) and
      concentration of zinc in whole blood, as well as dietary zinc intake. Searches
      were performed using Ovid MEDLINE, Embase (Ovid) and The Cochrane Library
      (CENTRAL). Observational studies conducted on diabetic and healthy adults, with
      data on dietary zinc intake and/or concentration of zinc in whole blood, were
      selected. The search strategy yielded 11,150 publications and the manual search
      6, of which 11 were included in the meta-analyses. Mean difference (MD) and 95%
      confidence interval (CI), were calculated using the generic inverse-variance
      method with random-effects models. Heterogeneity was assessed by the Cochran Q
      statistic and quantified by the I2 statistic. Meta-regressions and stratified
      analysis were used to examine whether any covariate had influence on the results.
      The pooled MD for the dietary zinc intake meta-analysis was -0.40 (95% CI: -1.59
      to 0.79; I2 = 61.0%). Differences between diabetic and non-diabetic subjects
      became significant in the presence of complications associated with diabetes (MD
      = -2.26; 95% CI: -3.49 to -1.02; I2 = 11.9%). Meta-regression showed that for
      each year since the diagnosis of diabetes the concentration of zinc in whole
      blood decreased in diabetic patients regarding healthy controls [MD
      (concentration of zinc in blood) = 732.61 + (-77.88303) * (duration of diabetes
      in years)], which is not generally explained by a lower intake of zinc.

PMID- 29452775
TI  - The link between depression and atherosclerosis through the pathways of
      inflammation and endothelium dysfunction.
AB  - A large body of evidence suggests that depression increases the risk of
      cardiovascular morbidity and mortality. The elevated risk associated with
      depression is not limited to clinical major depressive disorder but also extends
      to sub-syndromal depressive symptoms and constructs with overlapping
      characteristics, such as vital exhaustion. Multiple pathophysiological pathways
      are involved in the relationship between depressive symptoms and atherosclerosis
      and its clinical manifestations and progression. These underlying mechanisms are
      not yet fully understood and need further clarification. This review examines
      inflammation and endothelium dysfunction as potential biological factors involved
      in the relationship between depressive symptoms and atherosclerosis. It has been
      reported that systemic inflammation and psychological factors interact through
      complex pathophysiological and behavioral mechanisms and one question that has
      been raised concerns whether the inflammation drives depression or vice versa, or
      whether the association is merely coincidental. Although further investigation is
      needed, including well-designed prospective studies, to address this question
      thoroughly, it seems that there is a feedback relationship, although the
      biological pathways of each direction may be distinct.

PMID- 29452776
TI  - Women-specific risk factors for heart failure: A genetic approach.
AB  - Heart failure is a complex disease, which is presented differently by men and
      women. Several studies have shown that reproductive factors, such as age at
      natural menopause, parity and polycystic ovarian syndrome (PCOS), may play a role
      in the development of heart failure. Shared genetics may provide clues to
      underlying mechanisms; however, this has never been examined. Therefore, the aim
      of the current study was to explore whether any reproductive factor is
      potentially related to heart failure in women, based on genetic similarities.
      Conducting a systematic literature review, single nucleotide polymorphisms (SNPs)
      associated with reproductive factors, heart failure and its risk factors were
      extracted from recent genome-wide association studies. We tested whether there
      was any overlap between the SNPs and their proxies of reproductive risk factors
      with those known for heart failure or its risk factors. In total, 520 genetic
      variants were found that are associated with reproductive factors, namely age at
      menarche, age at natural menopause, menstrual cycle length, PCOS, preeclampsia,
      preterm delivery and spontaneous dizygotic twinning. For heart failure and
      associated phenotypes, 25 variants were found. Genetic variants for reproductive
      factors did not overlap with those for heart failure. However, age at menarche,
      gestational diabetes and PCOS were found to be genetically linked to risk factors
      for heart failure, such as atrial fibrillation, diabetes and smoking.
      Corresponding implicated genes, such as TNNI3K, ErbB3, MKL2, MTNR1B and PRKD1,
      may explain the associations between reproductive factors and heart failure.
      Exact effector mechanisms of these genes remain to be investigated further.

PMID- 29452777
TI  - Yoga for menopausal symptoms-A systematic review and meta-analysis.
AB  - OBJECTIVES: To systematically review and meta-analyze the effectiveness of yoga
      for menopausal symptoms. METHODS: Medline (via PubMed), the Cochrane Central
      Register of Controlled Trials, and Scopus were screened through to February 21,
      2017 for randomized controlled trials (RCTs) comparing the effects of yoga on
      menopausal symptoms to those of no treatment or active comparators. Standardized
      mean differences (SMD) and 95% confidence intervals (CI) were calculated. Two
      authors independently assessed risk of bias using the Cochrane risk of bias tool.
      RESULTS: Thirteen RCTs with 1306 participants were included. Compared with no
      treatment, yoga reduced total menopausal symptoms (SMD=-1.05; 95% CI -1.57 to 
      0.53), psychological (SMD=-0.75; 95% CI -1.17 to -0.34), somatic (SMD=-0.65; 95%
      CI -1.05 to -0.25), vasomotor (SMD=-0.76; 95% CI -1.27 to -0.25), and urogenital
      symptoms (SMD=-0.53; 95% CI -0.81 to -0.25). Compared with exercise controls,
      only an effect on vasomotor symptoms was found (SMD=-0.45; 95% CI -0.87 to 
      0.04). Effects were robust against selection bias, but not against detection and
      attrition bias. No serious adverse events were reported. CONCLUSION: Yoga seems
      to be effective and safe for reducing menopausal symptoms. Effects are comparable
      to those of other exercise interventions.

PMID- 29452778
TI  - Reproductive history and physical functioning in midlife: The Bogalusa Heart
      Study.
AB  - OBJECTIVE: To examine the relationship between reproductive history, pregnancy
      complications, and later physical function. STUDY DESIGN: The Bogalusa Heart
      Study is a long-running study of cardiovascular health in a semirural community.
      761 women were interviewed about their pregnancy history and complications, and
      underwent tests of physical function. Logistic models for dichotomous outcomes
      and linear models for continuous outcomes were used, adjusted for covariates.
      MAIN OUTCOME MEASURES: Overall scores on the Short Physical Performance Battery
      (SPPB), which combines scores for balance, gait speed, and chair stands.
      Additional tests were a 6-min walk, knee extension strength, grip strength, and a
      pegboard challenge. RESULTS: Nulliparity was associated with lower scores on the
      walking and balance portions of the SPPB, less distance covered in the 6-min
      walk, less knee and grip strength, and higher pegboard time, especially among pre
      menopausal women. A history of gestational diabetes was associated with more
      problems on the walk portion of the SPPB (aOR 2.44, 1.06-5.65), higher chair
      stand time, and lower knee strength. Young age at first birth (<16 or 18 years)
      was associated with a shorter chair stand time and a better pegboard score.
      CONCLUSIONS: Nulliparity was associated with worse physical functioning, while
      high parity and early pregnancy were not, suggesting that fertility is associated
      with better health later in life. Pregnancy complications were associated with
      worse physical functioning, even after controlling for body mass index. Future
      studies should attempt to establish the pathways by which reproductive health
      relates to overall physical functioning.

PMID- 29452779
TI  - Management of female stress urinary incontinence: A care pathway and update.
AB  - Stress urinary incontinence (SUI) is a condition characterized by an involuntary
      loss of urine occurring as result of an increase in intra-abdominal pressure due
      to effort or exertion or on sneezing or coughing. Estimates of its prevalence in
      the female population range from 10% to 40%. A literature search of the Medline,
      Cochrane library, EMBASE, NLH, ClinicalTrials.gov and Google Scholar databases
      was done up to July 2017, restricted to English-language articles, using terms
      related to SUI, medical therapy, surgical therapy and treatment options. The
      search terms included female stress urinary incontinence, mid-urethral sling,
      tension-free vaginal tape (TVT) and transobturator tape (TOT, TVT-O). Original
      articles, reviews and meta-analyses were included. Surgical therapy should be
      considered only after conservative therapies (e.g. an exercise programme or
      topical estrogens) have failed. Synthetic mid-urethral slings are the gold
      standard for the surgical treatment of SUI according to the 2016 guidelines of
      the European Society of Urology (ESU) and the 2017 position statement of the
      European Urogynaecological Association (EUA). The therapeutic options are
      numerous but further research into new therapeutic strategies is needed to
      achieve a better balance between efficacy and adverse events.

PMID- 29452780
TI  - Gender differences in the association of cognitive impairment with the risk of
      hip fracture in the older population.
AB  - OBJECTIVES: To test the hypothesis that differences by gender will be observed in
      the association of hip fracture risk with stages of cognitive impairment; and to
      explore the association between Petersen's "mild cognitive impairment" (MCI) and
      DSM-5 "mild neurocognitive disorder" (MND). STUDY DESIGN: A community sample of
      4803 individuals aged 55+ years was assessed in a two-phase case-finding enquiry
      in Zaragoza, Spain, and was followed up for 16 years. Medical and psychiatric
      history was collected with standardized instruments, including the Mini-Mental
      Status Examination (MMSE), Geriatric Mental State (GMS), History and Aetiology
      Schedule, and a Risk Factors Questionnaire. The statistical analysis included
      calculations of Hazard Ratios (HR) in multivariate Cox proportional hazards
      regression models. MAIN OUTCOME MEASURES: Identified cases of hip fracture,
      validated by blind researchers. RESULTS: In men, hip fracture risk was increased
      at the "mild" (HR=4.99 (1.39-17.91)) and at the "severe" (HR=9.31 (1.35-64.06))
      stages of cognitive impairment, indicated by MMSE performance. In contrast, in
      women no association could be documented at the "mild stage" (power=89%), and the
      association disappeared altogether at the "severe stage" in the final
      multivariate statistical model (power 100%). No association observed between hip
      fracture and mild cognitive impairment in both men (power=28% for P-MCI) and
      women (power=44% and 19% for Petersen's MCI and DSM-5 MND, respectively).
      CONCLUSIONS: Increased hip fracture risk was associated with "mild" stages of
      cognitive impairment in men, but not in women. To explore the potential
      association with the construct MCI or MND, studies with greater statistical power
      would be required.

PMID- 29452781
TI  - Physical training maintains or improves gait ability in long-term nursing home
      residents: A systematic review of randomized controlled trials.
AB  - Numerous studies have reported the benefits of physical exercise in older adults.
      However, studies performed in long-term nursing home (LTNH) residents are scarce.
      A literature search was conducted to identify physical exercise intervention
      studies that were randomized and controlled and that assessed gait ability in
      older LTNH residents using both walking speed and timed up-and-go (TUG) tests
      simultaneously. Together, these tests have been defined under the term "gait
      ability"; they are widely used to screen for impaired physical function, and can
      predict accelerated functional decline, difficulty with activities of daily
      living (ADL), falls, and disability in older adults. Multicomponent physical
      exercise programs are effective in improving or maintaining gait ability in older
      LTNH residents. The studies included in this review show substantial
      heterogeneity in terms of participant characteristics (age, baseline TUG
      performance, and walking speed), types of evaluated intervention (multicomponent
      and gait retraining programs), duration of the intervention (ranging from four
      weeks to 12 months), duration of physical exercise sessions (ranging from 30 min
      to 1 h), and exercise intensity (from 40% to 60-70% RM). Due to this
      heterogeneity, no firm conclusions can be drawn regarding the impact of exercise
      programs on gait ability in LTNH residents. However, the results of this review
      should encourage the gathering of additional evidence to support the use of
      multicomponent exercise programs by older individuals.

PMID- 29452782
TI  - Multimorbidity and quality of life at mid-life: A systematic review of general
      population studies.
AB  - There is substantial multimorbidity at mid-life but little is known about the
      strength of evidence on multimorbidity and health-related quality of life (HrQoL)
      at mid-life. This review addresses this gap, focusing on studies of the general
      population. PubMed, Web of Science, Embase and APA PsycNET databases were
      screened on 6 March 2017 for original research on multimorbidity and HrQoL in
      adults aged 40-65 years from the general population. Studies focused on index
      conditions, using single-item HrQoL measures, unlikely to represent the general
      population (e.g. primary care), and papers that were not in the English language
      were excluded. A narrative synthesis was presented due to heterogeneity in the
      measurement of multimorbidity. Of the 2557 articles, 83 underwent full text
      screening and 8 were included in the review. Included studies were of moderate to
      high quality and no exclusions were made on the basis of quality or bias.
      Multimorbidity was associated with poorer HrQoL at mid-life. Two cross-sectional
      studies found that adults with multimorbidity at early mid-life reported poorer
      HrQoL than adults with multimorbidity at late mid-life, while another found the
      reverse. Two distinct disease clusters were identified: mental health conditions
      and cardiovascular disease (CVD). Those in the mental health cluster reported
      poorer HrQoL than those in the CVD cluster, women more so than men. Limitations
      of the selected studies include lack of longitudinal evidence, use of self
      reported conditions and no assessment of disease severity. Multimorbidity is
      associated with poor HrQoL at mid-life at the population level, with some
      evidence of differences in association with age and disease cluster and sparse
      evidence on sex differences. Longitudinal research using a weighted disease
      severity index and multimorbidity trajectories is needed to strengthen the
      evidence base.

PMID- 29452783
TI  - Oxidative stress is increased in sarcopenia and associated with cardiovascular
      disease risk in sarcopenic obesity.
AB  - OBJECTIVES: To define whether circulating markers of oxidative stress correlate
      with sarcopenia in terms of glutathione balance and oxidative protein damage, and
      whether these biomarkers are associated with risk of cardiovascular disease
      (CVD). STUDY DESIGN: Population-based cross-sectional study. 115 out of 347
      elderly subjects were classified as non-sarcopenic non-obese (NS-NO), sarcopenic
      non-obese (S-NO), non-sarcopenic obese (NS-O), and sarcopenic obese (S-O). MAIN
      OUTCOME MEASUREMENTS: Sarcopenia was defined as a relative skeletal muscle mass
      index (RASM) <7.25kg/m2 for men or <5.67kg/m2 for women, while obesity was
      diagnosed in those presenting with% fat >27 for men or >38 for women. The CVD
      risk was estimated by the carotid intima-media thickness (IMT) and the Framingham
      score. Blood reduced glutathione (GSH), oxidized glutathione (GSSG), plasma
      malondialdehyde-(MDA) and 4-hydroxy-2,3-nonenal-(HNE) protein adducts were
      analyzed. RESULTS: Significantly greater blood GSSG/GSH ratio and plasma MDA/HNE
      protein adducts were observed in sarcopenic than in non-sarcopenic patients. A
      logistic regression model showed a close relationship between serum HNE and MDA
      adducts and sarcopenia (OR=1.133, 95% CI 1.057-1.215, and OR=1.592, 95% CI 1.015
      1.991, respectively). Linear and logistic regression analysis evidenced strong
      associations between the IMT or the Framingham CVD risk category and blood
      GSSG/GSH or serum HNE protein adducts in the S-O group. CONCLUSION: Circulating
      markers of oxidative stress are increased in sarcopenia and related to CVD risk
      in sarcopenic obesity, suggesting that redox balance analysis would be a useful
      part of a multidimensional evaluation in aging. Further research is encouraged to
      support interventional strategies to correct redox imbalance, which might
      contribute to the prevention or at least limitation of sarcopenia and its co
      morbidities.

PMID- 29452784
TI  - Abdominal aortic aneurysm: Sex differences.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) predominantly affects an elderly male
      population. Even so, AAA appears more detrimental in women, who experience a
      higher risk of aneurysm rupture and a worse outcome after surgery than men. Why
      women are privileged from yet are worse off once affected has been attributed to
      an effect of sex hormones. This review summarizes the knowledge of sex
      differences in AAA and addresses the changes in the aneurysm wall from a gender
      perspective. METHOD: Standard reporting guidelines set by the PRISMA Group were
      followed to identify studies examining AAA from a gender perspective. Relevant
      reports were identified using two electronic databases: PubMed and Web of
      Science. The systematic search was performed in two stages: firstly, using the
      terms AAA and gender/sex/women; and secondly, adding the terms "elastin",
      "collagen" and "vascular smooth muscle cells", in order to filter the search for
      studies relevant to our focus on the aneurysm wall. CONCLUSION: Current studies
      support the theory that sex has an effect on aneurysm formation, yet are
      inconclusive about whether or not aneurysm formation is dependent on female/male
      sex hormones or a lack thereof. The studies in women are scarce and out of those
      most reports primarily address other end-points, which limit their ability to
      illuminate an effect of sex on aneurysm formation. The complexity of the human
      menstrual cycle and menopausal transition are difficult to mimic in animal
      models, which limit their applicability to AAA formation in humans.

PMID- 29452785
TI  - The risks of sarcopenia, falls and fractures in patients with type 2 diabetes
      mellitus.
AB  - Fracture risk in patients with type 2 diabetes mellitus (T2DM) is increased, and
      the mechanism is multifactorial. Recent research on T2DM-induced bone fragility
      shows that bone mineral density (BMD) is often normal or even slightly elevated.
      However, bone turnover may be decreased and bone material and microstructural
      properties are altered, especially when microvascular complications are present.
      Besides bone fragility, extra-skeletal factors leading to an increased propensity
      to experience falls may also contribute to the increased fracture risk in T2DM,
      such as peripheral neuropathy, retinopathy and diabetes medication (e.g. insulin
      use). One of the probable additional contributing factors to the increased fall
      and fracture risks in T2DM is sarcopenia, the age-related decline in skeletal
      muscle mass, quality and function. Although the association between sarcopenia,
      fall risk, and fracture risk has been studied in the general population, few
      studies have examined the association between T2DM and muscle tissue and the
      risks of falls and fractures. This narrative review provides an overview of the
      literature regarding the multifactorial mechanisms leading to increased fracture
      risk in patients with T2DM, with a focus on sarcopenia and falls.

PMID- 29452786
TI  - Preliminary results of a single-arm pilot study to assess the safety and efficacy
      of visnadine, prenylflavonoids and bovine colostrum in postmenopausal sexually
      active women affected by vulvovaginal atrophy.
AB  - This single-arm pilot study enrolled 47 post-menopausal women affected by
      vulvovaginal atrophy (VVA). The Vaginal Health Index Score (VHIS) was evaluated
      for all women and all completed the Female Sexual Function Index (FSFI)
      questionnaire at baseline (T0) and after 15 days of vaginal cream treatment with
      one application per day (T1). Following treatment there was a significant
      improvement in all VHIS parameters and total score (p < 0.0001). Similarly, there
      was a significant improvement on four FSFI domains (lubrication, orgasm,
      satisfaction and pain) and total score (p = 0.001). None of the patients reported
      any local or systemic side-effects during treatment.

PMID- 29452787
TI  - A modelling study to evaluate the costs and effects of lowering the starting age
      of population breast cancer screening.
AB  - BACKGROUND: Because the incidence of breast cancer increases between 45 and
      50years of age, a reconsideration is required of the current starting age
      (typically 50years) for routine mammography. Our aim was to evaluate the
      quantitative benefits, harms, and cost-effectiveness of lowering the starting age
      of breast cancer screening in the Dutch general population. METHODS: Economic
      modelling with a lifelong perspective compared biennial screening for women aged
      48-74years and for women aged 46-74years with the current Dutch screening
      programme, which screen women between the ages of 50 and 74years. Tumour deaths
      prevented, years of life saved (YOLS), false-positive rates, radiation-induced
      tumours, costs and incremental cost-effectiveness ratios (ICERs) were evaluated.
      RESULTS: Starting the screening at 48 instead of 50 years of age led to increases
      in: the number of small tumours detected (4.0%), tumour deaths prevented (5.6%),
      false positives (9.2%), YOLS (5.6%), radiation-induced tumours (14.7%), and costs
      (4.1%). Starting the screening at 46 instead of 48 years of age increased the
      number of small tumours detected (3.3%), tumour deaths prevented (4.2%), false
      positives (8.8%), YOLS (3.7%), radiation-induced tumours (15.2%), and costs
      (4.0%). The ICER was ?5600/YOLS for the 48-74 scenario and ?5600/YOLS for the 46
      74 scenario. CONCLUSIONS: Women could benefit from lowering the starting age of
      screening as more breast cancer deaths would be averted. Starting regular breast
      cancer screening earlier is also cost-effective. As the number of additional
      expected harms is relatively small in both the scenarios examined, and the
      difference in ICERs is not large, introducing two additional screening rounds is
      justifiable.

PMID- 29452788
TI  - Understanding pre-, peri- and post-menopausal women's intentions to perform
      muscle-strengthening activities using the Theory of Planned Behaviour.
AB  - Although physical activity guidelines recommend muscle-strengthening activities
      (MSA), public health initiatives tend to focus on increasing aerobic activity and
      fail to mention MSA. This study sought to identify the issues influencing pre-,
      peri- and post-menopausal women's intentions to perform MSA with a view to
      informing future interventions for these populations. Mixed methods guided by the
      Theory of Planned Behaviour (TPB) were used to explore factors that influence
      women's intentions to perform MSA. In stage one, 34 women participated in either
      a focus group or interview. Discussions were transcribed verbatim and analysed
      based on menopausal status using a deductive approach. In stage two, 186 women (M
      = 47 years, SD = 9) completed a questionnaire to assess participant demographics,
      levels of MSA, affective and instrumental attitudes, injunctive and descriptive
      norms, self-efficacy and perceived behavioural control. Quantitative data were
      analysed using descriptive statistics, bivariate correlations, regression
      analyses and analysis of variances. Behavioural beliefs were: improved muscular
      health; psychological benefits; improved body shape. Normative beliefs were:
      health professionals; family members; work colleagues. Control beliefs were:
      equipment; motivation; time constraints; knowledge; physical capability; fear of
      judgement. However, these beliefs were not well established. Self-efficacy was
      the strongest predictor of intentions (spc2 = 0.11) followed by affective
      attitudes (spc2 = 0.09), with no significant differences on TPB variables between
      groups. If rising rates of musculoskeletal conditions in women are to be
      prevented, there is an urgent need to increase women's knowledge of recommended
      levels of muscle strengthening, with a view to promoting positive attitudes and
      enhancing women's sense of self-efficacy across all menopausal phases.

PMID- 29452789
TI  - Informal caregiving and metabolic markers in the UK Household Longitudinal Study.
AB  - OBJECTIVES: Informal caregiving is associated with poorer mental and physical
      health. Little research has yet focused on objectively measured health risk
      factors, such as metabolic markers. The aim of this study was to investigate
      whether informal caregiving was associated with markers of metabolism in a large,
      representative UK longitudinal study. We also investigated whether more intensive
      caregiving, as indicated by more caregiving hours, was associated with a less
      favourable metabolic profile. STUDY DESIGN/OUTCOME MEASURES: Using data on 9408
      participants aged 16+ from the UK Household Longitudinal Study, we explored the
      relationship between caregiving and metabolic markers (blood pressure, total and
      high density lipoprotein cholesterol, glycated haemoglobin and triglycerides). We
      additionally investigated the importance of caregiving intensity (number of hours
      spent caregiving per week). Associations between caregiving/caregiving intensity
      and metabolic markers were tested using gender-stratified linear regression
      models adjusted for age, household income, education, social class, chronic
      illness, number of dependent children in the household, body mass index and
      partnership status. RESULTS: Men who were informal caregivers had higher total
      cholesterol levels than non-caregivers (3.25% higher, 95% CI: 0.07, 6.53). Women
      caregivers also had higher total cholesterol levels and women providing intensive
      care (over 20 h per week) had higher triglyceride levels (19.91% higher, 95% CI:
      7.22, 34.10) and lower levels of high density lipoprotein cholesterol (8.46%
      lower, 95% CI: 14.51, 1.99); however, associations for women were attenuated in
      our final models. CONCLUSIONS: Informal caregiving is associated with less
      favourable lipid profiles. This may be one mechanism through which informal
      caregiving is associated with increased disease risk. The health of informal
      caregivers should be a priority for public health.

PMID- 29452790
TI  - [Letter on the article: "Absence of proof does not constitute proof of absence.
      On the misuse of 'evidence-based medicine'"].

PMID- 29452791
TI  - Untapped Reserves: Controlling Primordial Follicle Growth Activation.
AB  - Even with the benefit of assisted reproductive technologies (ART), many women are
      unable to conceive and deliver healthy offspring. One common cause of infertility
      is the inability to produce eggs capable of contributing to live birth. This can
      occur despite standard-of-care treatment to maximize the recovery of eggs from
      growing ovarian follicles. Dormant primordial follicles in the human ovary are a
      'reserve ' that can be exploited clinically to overcome this problem. We discuss
      how controlling primordial follicle growth activation (PFGA) can produce
      increased numbers of high-quality eggs available for fertility treatment(s). We
      consider the state of the art in interventions used to control PFGA, and consider
      genetic and epigenetic strategies on the horizon that might improve compromised
      oocyte quality to increase live births.

PMID- 29452793
TI  - Improving the evidence-base for preoperative cardiopulmonary exercise testing.

PMID- 29452792
TI  - Clinical and radiological features of spinal extradural arachnoid cysts: Valve
      like mechanism involving the nerve root fiber as a possible cause of cyst
      expansion.
AB  - BACKGROUND: Although a valve-like mechanism has been proposed for expansion of
      spinal extradural arachnoid cysts (SEACs), the detailed mechanism remains
      unclear. Moreover, closure of the communication site is essential during surgery,
      but the method to identify the communication site remains unclear. The aim of
      this study was to determine the detailed mechanism of expanding SEACs through
      retrospective analysis of SEAC cases undergoing surgery and to elucidate the
      characteristics of the communication sites. METHODS: The authors retrospectively
      evaluated 12 patients with SEACs who underwent surgery between 2000 and 2014 and
      analyzed their perioperative findings. RESULTS: Dural defects were detected in 11
      out of 12 patients, and a valve-like mechanism was observed in 7 patients,
      wherein a nerve root fiber moved back and forth through the dural defect along
      with the flow of cerebrospinal fluid (CSF) between the intradural space and the
      extradural arachnoid cysts. The dural defect was located at the thoracolumbar
      junction in 7 patients, below the distal end of the bridging ossification in 2,
      at the level of vertebral wedge deformity in 2, and at the level of disc
      herniation in 1. CONCLUSIONS: A valve-like mechanism was observed in 7 of the 12
      patients, which suggests that it could serve as a mechanism of SEAC formation.
      The communication sites were variously located at the end of ossification in
      patients with diffuse idiopathic skeletal hyperostosis (DISH), wedge deformity of
      the vertebral body, or disc herniation, indicating the contribution of mechanical
      stress to SEAC formation.

PMID- 29452794
TI  - Norepinephrine improves cardiac function during septic shock, but why?

PMID- 29452795
TI  - Schrodinger's cat: anaesthetised and not!

PMID- 29452796
TI  - One to rule them all?

PMID- 29452797
TI  - Reconceptualising stroke research to inform the question of anaesthetic
      neurotoxicity.

PMID- 29452798
TI  - "Pain as the fifth vital sign" and dependence on the "numerical pain scale" is
      being abandoned in the US: Why?

PMID- 29452799
TI  - How to prevent medication errors in the operating room? Take away the human
      factor.

PMID- 29452800
TI  - Removal of a supraglottic airway in children with increased risk of respiratory
      complications: is timing of removal not important?

PMID- 29452801
TI  - Systematic review of the effects of intensive-care-unit noise on sleep of healthy
      subjects and the critically ill.
AB  - Intensive-care-unit (ICU) patients exhibit disturbed sleeping patterns, often
      attributed to environmental noise, although the relative contribution of noise
      compared to other potentially disrupting factors is often debated. We therefore
      systematically reviewed studies of the effects of ICU noise on the quality of
      sleep to determine to what extent noise explains the observed sleep disruption,
      using the Cochrane Collaboration method for non-randomized studies. Searches in
      Scopus, PubMed, Embase, CINAHL, Web of Science, and the Cochrane Library were
      conducted until May 2017. Twenty papers from 18 studies assessing sleep of adult
      patients and healthy volunteers in the ICU environment, whilst recording sound
      levels, were included and independently reviewed by two reviewers. We found that
      the numbers of arousals between the baseline and the ICU noise condition in
      healthy subjects differed significantly (mean difference 9.59; 95% confidence
      interval 2.48-16.70). However, there was considerable heterogeneity between
      studies (I2 94%, P < 0.00001), and all studies suffered from a considerable risk
      of bias. The meta-analysis of results was hampered by widely varying definitions
      of sound parameters between studies and a general lack of detailed description of
      methods used. It is, therefore, currently impossible to quantify the extent to
      which noise contributes to sleep disruption among ICU patients, and thus, the
      potential benefit from noise reduction remains unclear. Regardless, the majority
      of the observed sleep disturbances remain unexplained. Future studies should,
      therefore, also focus on more intrinsic sleep-disrupting factors in the ICU
      environment.

PMID- 29452802
TI  - Moving to human trials for argon neuroprotection in neurological injury: a
      narrative review.
AB  - Despite the global burden of brain injury, neuroprotective agents remain elusive.
      There are no clinically effective therapies which reduce mortality or improve
      long-term cognitive outcome. Ventilation could be an easily modifiable variable
      in resuscitation; gases are relatively simple to administer. Xenon is the
      prototypic agent of a new generation of experimental treatments which show
      promise. However, use is hindered by its prohibitive cost and anaesthetic
      properties. Argon is an attractive option, being cheaper, easy to transport, non
      sedating, and mechanistically distinct from xenon. In vitro and in vivo models
      provide evidence of argon reducing brain injury, with improvements in
      neurocognitive, histological, and biomarker metrics, as well as improved
      survival. Current data suggest that the effect of argon is mediated via the toll
      like receptors 2 and 4, the extracellular signal-regulated kinase 1/2, and
      phosphatidylinositol 3 kinase (PI-3K)-AKT pathways. Ventilation with argon
      appears to be safe in pigs and preliminary human trials. Given recent evidence
      that arterial hyperoxia may be harmful, the supplementation of high-concentration
      argon may not necessitate changes to clinical practice. Given the logistic
      benefits, and the evidence for argon neuroprotection summarized in this
      manuscript, we believe that the time has come to consider developing Phase II
      clinical trials to assess its benefit in acute neurological injury.

PMID- 29452803
TI  - Preoperative fasting in children: review of existing guidelines and recent
      developments.
AB  - The current guidelines for preoperative fasting recommend intervals of 6, 4, and
      2 h (6-4-2) of fasting for solids, breast milk, and clear fluids, respectively.
      The objective is to minimize the risk of pulmonary aspiration of gastric
      contents, but also to prevent unnecessarily long fasting intervals. Pulmonary
      aspiration is rare and associated with nearly no mortality in paediatric
      anaesthesia. The incidence may have decreased during the last decades, judging
      from several audits published recently. However, several reports of very long
      fasting intervals have also been published, in spite of the implementation of the
      6-4-2 fasting regimens. In this review, we examine the physiological basis for
      various fasting recommendations, the temporal relationship between fluid intake
      and residual gastric content, and the pathophysiological effects of preoperative
      fasting, and review recent publications of various attempts to reduce the
      incidence of prolonged fasting in children. The pros and cons of the current
      guidelines will be addressed, and possible strategies for a future revision will
      be suggested.

PMID- 29452804
TI  - Inter-observer reliability of preoperative cardiopulmonary exercise test
      interpretation: a cross-sectional study.
AB  - BACKGROUND: Despite the increasing importance of cardiopulmonary exercise testing
      (CPET) for preoperative risk assessment, the reliability of CPET interpretation
      is unclear. We aimed to assess inter-observer reliability of preoperative CPET.
      METHODS: We conducted a prospective, multi-centre, observational study of
      preoperative CPET interpretation. Participants were professionals with previous
      experience or training in CPET, assessed by a standardized questionnaire. Each
      participant interpreted 100 tests using standardized software. The CPET variables
      of interest were oxygen consumption at the anaerobic threshold (AT) and peak
      oxygen consumption (VO2 peak). Inter-observer reliability was measured using
      intra-class correlation coefficient (ICC) with a random effects model. Results
      are presented as ICC with 95% confidence interval, where ICC of 1 represents
      perfect agreement and ICC of 0 represents no agreement. RESULTS: Participants
      included 8/28 (28.6%) clinical physiologists, 10 (35.7%) junior doctors, and 10
      (35.7%) consultant doctors. The median previous experience was 140 (inter
      quartile range 55-700) CPETs. After excluding the first 10 tests
      (acclimatization) for each participant and missing data, the primary analysis of
      AT and VO2 peak included 2125 and 2414 tests, respectively. Inter-observer
      agreement for numerical values of AT [ICC 0.83 (0.75-0.90)] and VO2 peak [ICC
      0.88 (0.84-0.92)] was good. In a post hoc analysis, inter-observer agreement for
      identification of the presence of a reportable AT was excellent [ICC 0.93 (0.91
      0.95)] and a reportable VO2 peak was moderate [0.73 (0.64-0.80)]. CONCLUSIONS:
      Inter-observer reliability of interpretation of numerical values of two commonly
      used CPET variables was good (>80%). However, inter-observer agreement regarding
      the presence of a reportable value was less consistent.

PMID- 29452805
TI  - Perioperative cardiopulmonary exercise testing (CPET): consensus clinical
      guidelines on indications, organization, conduct, and physiological
      interpretation.
AB  - The use of perioperative cardiopulmonary exercise testing (CPET) to evaluate the
      risk of adverse perioperative events and inform the perioperative management of
      patients undergoing surgery has increased over the last decade. CPET provides an
      objective assessment of exercise capacity preoperatively and identifies the
      causes of exercise limitation. This information may be used to assist clinicians
      and patients in decisions about the most appropriate surgical and non-surgical
      management during the perioperative period. Information gained from CPET can be
      used to estimate the likelihood of perioperative morbidity and mortality, to
      inform the processes of multidisciplinary collaborative decision making and
      consent, to triage patients for perioperative care (ward vs critical care), to
      direct preoperative interventions and optimization, to identify new
      comorbidities, to evaluate the effects of neoadjuvant cancer therapies, to guide
      prehabilitation and rehabilitation, and to guide intraoperative anaesthetic
      practice. With the rapid uptake of CPET, standardization is key to ensure valid,
      reproducible results that can inform clinical decision making. Recently, an
      international Perioperative Exercise Testing and Training Society has been
      established (POETTS www.poetts.co.uk) promoting the highest standards of care for
      patients undergoing exercise testing, training, or both in the perioperative
      setting. These clinical cardiopulmonary exercise testing guidelines have been
      developed by consensus by the Perioperative Exercise Testing and Training Society
      after systematic literature review. The guidelines have been endorsed by the
      Association of Respiratory Technology and Physiology (ARTP).

PMID- 29452806
TI  - Steroid administration after anaesthetic induction with etomidate does not reduce
      in-hospital mortality or cardiovascular morbidity after non-cardiac surgery.
AB  - BACKGROUND: We tested the primary hypothesis that corticosteroid administration
      after etomidate exposure reduces a composite of in-hospital mortality and
      cardiovascular morbidity after non-cardiac surgery. METHODS: We evaluated ASA
      physical status III and IV patients who had non-cardiac surgery with general
      anaesthesia at the Cleveland Clinic. Amongst 4275 patients in whom anaesthesia
      was induced with etomidate, 804 were also given steroid intraoperatively, mostly
      dexamethasone at a median dose of 6 mg. We successfully matched 582 steroid
      patients with 1023 non-steroid patients. The matched groups were compared on
      composite of in-hospital mortality and cardiovascular morbidity using a
      generalized-estimating-equation model. Secondly, the matched groups were compared
      on length of hospital stay using a Cox proportional hazard model, and were
      descriptively compared on intraoperative blood pressures using a standardized
      difference. RESULTS: There was no significant association between intraoperative
      steroid administration after anaesthetic induction with etomidate and the
      composite of in-hospital mortality or cardiovascular morbidity; the estimated
      common odds ratio across the two components of the composite was 0.86 [95%
      confidence interval (CI): 0.64, 1.16] for steroid vs non-steroid, P=0.33. The
      duration of postoperative hospitalisation was significantly shorter amongst
      steroid patients [median (Q1, Q3): 6 (3, 10) days] than non-steroid patients [7
      (4, 11) days], with an estimated hazard ratio of 0.89 (0.80, 0.98) for steroid vs
      non-steroid, P=0.01. Intraoperative blood pressures were similar in steroid and
      non-steroid patients. CONCLUSIONS: Steroid administration after induction of
      anaesthesia with etomidate did not reduce mortality or cardiovascular morbidity.

PMID- 29452807
TI  - Incidence and outcomes of sepsis after cardiac surgery as defined by the Sepsis-3
      guidelines.
AB  - BACKGROUND: The Sepsis-3 guidelines diagnose sepsis based on organ dysfunction in
      patients with either proven or suspected infection. The objective of this study
      was to assess the incidence and outcomes of sepsis diagnosed using these
      guidelines in patients in a cardiac intensive care unit (CICU) after cardiac
      surgery. METHODS: Daily sequential organ failure assessment (SOFA) scores were
      calculated for 2230 consecutive adult cardiac surgery patients between January
      2013 and May 2015. Patients with an increase in SOFA score of >=2 and suspected
      or proven infection were identified. The length of CICU stay, 30-day mortality
      and 2-yr survival were compared between groups. Multivariable linear regression,
      multivariable logistic regression, and Cox proportional hazards regression were
      used to adjust for possible confounders. RESULTS: Sepsis with suspected or proven
      infection was diagnosed in 104 (4.7%) and 107 (4.8%) patients, respectively.
      After adjustment for confounding variables, sepsis with suspected infection was
      associated with an increased length of CICU stay of 134.1h (95% confidence
      interval (CI) 99.0-168.2, P<0.01) and increased 30-day mortality risk (odds ratio
      3.7, 95% CI 1.1-10.2, P=0.02). Sepsis with proven infection was associated with
      an increased length of CICU stay of 266.1h (95% CI 231.6-300.7, P<0.01) and
      increased 30-day mortality risk (odds ratio 6.6, 95% CI 2.6-15.7, P<0.01).
      CONCLUSIONS: Approximately half of sepsis diagnoses were based on proven
      infection and half on suspected infection. Patients diagnosed with sepsis using
      the Sepsis-3 guidelines have significantly worse outcomes after cardiac surgery.
      The Sepsis-3 guidelines are a potentially useful tool in the management of sepsis
      following cardiac surgery.

PMID- 29452808
TI  - Norepinephrine exerts an inotropic effect during the early phase of human septic
      shock.
AB  - BACKGROUND: We conducted this study to investigate whether norepinephrine
      increases cardiac contractility when administered during the early phase of
      septic shock. METHODS: We studied 38 patients with septic shock who had been
      resuscitated for <3 h and whose mean arterial pressure (MAP) remained <65 mm Hg.
      Echocardiographic variables were obtained before (T0) and after either initiation
      or an increase in the dose of a norepinephrine infusion to increase MAP to >= 65
      mm Hg (T1). We collected left ventricular ejection fraction (LVEF), velocity-time
      integral of the left ventricular outflow tract (VTI), tissue Doppler imaging of
      mean systolic velocity of the lateral tricuspid annulus (Sa) and of the lateral
      mitral annulus (Sm), and tricuspid annular plane systolic excursion (TAPSE).
      RESULTS: There were significant (P<0.05) increases from T0 to T1 in MAP [mean
      (sd): from 56 (7) to 80 (9) mm Hg], LVEF [from 49 (13) to 56 (13)%], VTI [from 18
      (5) to 20 (6) cm], Sm [from 10.8 (5.1) to 12.1 (5.0) cm s-1], TAPSE [from 1.8
      (0.5) to 2.0 (0.5) cm], and Sa [from 13.0 (5.6) to 15.1 (6.4) cm s-1]. In the
      subgroup of 15 patients with LVEF <=45%, significant increases in VTI [from 16
      (8) to 18 (7) cm] and in LVEF [from 36 (7) to 44 (10)%] were observed.
      CONCLUSIONS: Norepinephrine administration during early resuscitation in patients
      with septic shock increased the cardiac systolic function despite the presumed
      increase in left ventricular afterload secondary to the increased arterial
      pressure. Whether such an effect persists over time remains to be evaluated.
      CLINICAL TRIAL REGISTRATION: NCT02750683.

PMID- 29452809
TI  - Test of neural inertia in humans during general anaesthesia.
AB  - BACKGROUND: Neural inertia is defined as the tendency of the central nervous
      system to resist transitions between arousal states. This phenomenon has been
      observed in mice and Drosophila anaesthetized with volatile anaesthetics: the
      effect-site concentration required to induce anaesthesia in 50% of the population
      (C50) was significantly higher than the effect-site concentration for 50% of the
      population to recover from anaesthesia. We evaluated this phenomenon in humans
      using propofol or sevoflurane (both with or without remifentanil) as anaesthetic
      agents. METHODS: Thirty-six healthy volunteers received four sessions of
      anaesthesia with different drug combinations in a step-up/step-down design.
      Propofol or sevoflurane was administered with or without remifentanil. Serum
      concentrations of propofol and remifentanil were measured from arterial blood
      samples. Loss and return of responsiveness (LOR-ROR), response to pain (PAIN),
      Patient State Index (PSI) and spectral edge frequency (SEF) were modeled with
      NONMEM(r). RESULTS: For propofol, the C50 for induction and recovery of
      anaesthesia was not significantly different across the different endpoints. For
      sevoflurane, for all endpoints except SEF, significant differences were found.
      For some endpoints (LOR and PAIN) the difference was significant only when
      sevoflurane was combined with remifentanil. CONCLUSIONS: Our results nuance
      earlier findings with volatile anaesthetics in mice and Drosophila.
      Methodological aspects of the study, such as the measured endpoint, influence the
      detection of neural inertia. A more thorough definition of neural inertia, with a
      robust methodological framework for clinical studies is required to advance our
      knowledge of this phenomenon. CLINICAL TRIAL REGISTRATION: NCT 02043938.

PMID- 29452810
TI  - Interleukin-6 is both necessary and sufficient to produce perioperative
      neurocognitive disorder in mice.
AB  - BACKGROUND: Perioperative neurocognitive disorders (PND) result in long-term
      morbidity and mortality with no effective interventions available. Because
      interleukin-6 (IL-6), a pro-inflammatory cytokine, is consistently up-regulated
      by trauma, including after surgery, we determined whether IL-6 is a putative
      therapeutic target for PND in a mouse model. METHODS: Following institutional
      approval, adult (12-14 weeks) male C57/Bl6 mice were pretreated with the IL-6
      receptor (IL6R) blocking antibody tocilizumab prior to open tibia fracture with
      internal fixation under isoflurane anaesthesia. Inflammatory and behavioural
      responses in a trace fear conditioning (TFC) paradigm were assessed
      postoperatively. Separately, the effects of IL-6 administration or of depletion
      of bone marrow-derived monocytes (BM-DMs) with clodrolip on the inflammatory and
      behavioural responses were assessed. Blood brain barrier disruption, hippocampal
      microglial activation, and infiltration of BM-DMs were each assessed following IL
      6 administration. RESULTS: The surgery-induced decrement in freezing time in the
      TFC assay, indicative of cognitive decline, was attenuated by tocilizumab
      (P<0.01). The surgery-induced increase in pro-inflammatory mediators was
      significantly reduced by tocilizumab. Exogenously administered IL-6 significantly
      impaired freezing behaviour (P<0.05) and up-regulated pro-inflammatory cytokines;
      both responses were prevented by depletion of BM-DMs. IL-6 disrupted the blood
      brain barrier, and increased hippocampal activation of microglia and infiltration
      of BM-DMs. CONCLUSIONS: IL-6 is both necessary and sufficient to produce
      cognitive decline. Following further preclinical testing of its perioperative
      safety, the IL6R blocker tocilizumab is a candidate for prevention and/or
      treatment of PND.

PMID- 29452811
TI  - Effects on adult cognitive function after neonatal exposure to clinically
      relevant doses of ionising radiation and ketamine in mice.
AB  - BACKGROUND: Radiological methods for screening, diagnostics and therapy are
      frequently used in healthcare. In infants and children, anaesthesia/sedation is
      often used in these situations to relieve the patients' perception of stress or
      pain. Both ionising radiation (IR) and ketamine have been shown to induce
      developmental neurotoxic effects and this study aimed to identify the combined
      effects of these in a murine model. METHODS: Male mice were exposed to a single
      dose of ketamine (7.5 mg kg-1 body weight) s.c. on postnatal day 10. One hour
      after ketamine exposure, mice were whole body irradiated with 50-200 mGy gamma
      radiation (137Cs). Behavioural observations were performed at 2, 4 and 5 months
      of age. At 6 months of age, cerebral cortex and hippocampus tissue were analysed
      for neuroprotein levels. RESULTS: Animals co-exposed to IR and ketamine displayed
      significant (P<=0.01) lack of habituation in the spontaneous behaviour test, when
      compared with controls and single agent exposed mice. In the Morris Water Maze
      test, co-exposed animals showed significant (P<=0.05) impaired learning and
      memory capacity in both the spatial acquisition task and the relearning test
      compared with controls and single agent exposed mice. Furthermore, in co-exposed
      mice a significantly (P<=0.05) elevated level of tau protein in cerebral cortex
      was observed. Single agent exposure did not cause any significant effects on the
      investigated endpoints. CONCLUSION: Co-exposure to IR and ketamine can aggravate
      developmental neurotoxic effects at doses where the single agent exposure does
      not impact on the measured variables. These findings show that estimation of risk
      after paediatric low-dose IR exposure, based upon radiation dose alone, may
      underestimate the consequences for this vulnerable population.

PMID- 29452812
TI  - Randomised trial comparing forced-air warming to the upper or lower body to
      prevent hypothermia during thoracoscopic surgery in the lateral decubitus
      position.
AB  - BACKGROUND: In the supine position, forced-air warming is more effective on the
      lower body than on the upper body to prevent intraoperative hypothermia. However,
      it is unknown in the lateral decubitus position. We thus compared forced-air
      warming on the upper and lower bodies in the lateral position. METHODS: Patients
      (n=123) were randomised to receive forced-air warming on the upper body or lower
      body during thoracoscopic surgery in the lateral position. We measured the
      nasopharyngeal temperature at 0, 30, 60, 90, and 120 min after lateral
      positioning during surgery and the infrared tympanic membrane temperature at 0,
      30, 60, 90, and 120 min after surgery. Patients received both upper and lower
      body warming at a temperature of <35.5 degrees C. The primary outcome was the
      incidence of intraoperative hypothermia with a temperature of <36.0 degrees C.
      RESULTS: Intraoperative hypothermia was less frequent with the upper body warming
      than with the lower body warming {21/62 vs 35/61, risk ratio [95% confidence
      interval (CI)] 0.6 (0.4-0.9), P=0.011}. The intraoperative temperature was higher
      with the upper body warming than with the lower body warming at 30 (P=0.002), 60
      (P<0.001), and 90 (P<0.001) min after lateral positioning, and the postoperative
      temperature was higher at 0 (P<0.001) and 30 (P=0.001) min after surgery. Fewer
      patients received both upper and lower body warming in the upper body warming
      group than in the lower body warming group during surgery (1 vs 7, P=0.032).
      CONCLUSIONS: Forced-air warming was more effective on the upper body than on the
      lower body to prevent hypothermia during thoracoscopic surgery in the lateral
      decubitus position. CLINICAL TRIAL REGISTRATION: NCT02993666.

PMID- 29452813
TI  - Incidence, characteristics, and predictive factors for medication errors in
      paediatric anaesthesia: a prospective incident monitoring study.
AB  - BACKGROUND: Medication errors are not uncommon in hospitalized patients.
      Paediatric patients may have increased risk for medication errors related to
      complexity of weight-based dosing calculations or problems with drug preparation
      and dilution. This study aimed to determine the incidence of medication errors in
      paediatric anaesthesia in a university paediatric hospital, and to identify their
      characteristics and potential predictive factors. METHODS: This prospective
      incident monitoring study was conducted between November 2015 and January 2016 in
      an exclusively paediatric surgical centre. Children <18 yr undergoing general
      anaesthesia were consecutively included. For each procedure, an incident form was
      completed by the attending anaesthetist on an anonymous and voluntary basis.
      RESULTS: Incident forms were completed in 1400 (73%) of the 1925 general
      anaesthetics performed during the study period with 37 reporting at least one
      medication error (2.6%). Drugs most commonly involved in medication errors were
      opioids and antibiotics. Incorrect dose was the most frequently reported type of
      error (n=27, 67.5%), with dilution error involved in 7/27 (26%) cases of
      incorrect dose. Duration of procedure >120 min was the only factor independently
      associated with medication error [adjusted odds ratio: 4 (95% confidence
      interval: 2-8); P=0.0001]. CONCLUSIONS: Medication errors are not uncommon in
      paediatric anaesthesia. Identification of the mechanisms related to medication
      errors might allow preventive measures that can be assessed in further studies.

PMID- 29452814
TI  - Deep or awake removal of laryngeal mask airway in children at risk of respiratory
      adverse events undergoing tonsillectomy-a randomised controlled trial.
AB  - BACKGROUND: Laryngeal mask airways (LMA) are widely used during tonsillectomies.
      Contrasting evidence exists regarding the timing of the removal and the risk of
      perioperative respiratory adverse events. We assessed whether the likelihood of
      perioperative respiratory adverse events is influenced by the timing of LMA
      removal in children with at least one risk factor for these events. METHODS:
      Participants (n=290, 0-16 yr) were randomised to have their LMA removed either
      deep (in theatre by anaesthetist at end-tidal sevoflurane >1 minimum alveolar
      concentration) or awake (in theatre by anaesthetist or in postanaesthesia care
      unit by anaesthetist or trained nurse). The primary outcome was the occurrence of
      perioperative respiratory adverse events over the whole emergence and
      postanaesthesia care unit phases of anaesthesia. The secondary outcome was the
      occurrence of perioperative respiratory adverse events over the distinct phases
      of emergence and postanaesthesia care unit. RESULTS: Data from 283 participants
      were analysed. PRIMARY OUTCOME: even though a higher occurrence of adverse events
      was observed in the awake group, no evidence for a difference was found [45% vs
      35%, odds ratio (OR): 1.5, 95% confidence interval (CI): 0.9-2.5, P=0.09].
      Secondary outcome: there was no evidence for a difference between the groups
      during emergence [19 (14%) deep vs 25 (18%) awake, OR: 0.74, 95%CI: 0.39-1.42,
      P=0.37]. However, in the postanaesthesia care unit, children with an awake rather
      than deep removal experienced significantly more adverse events [55 (39%) vs 37
      (26%); OR: 1.85, 95%CI: 1.12-3.07, P=0.02]. CONCLUSION: We found no evidence for
      a difference in the timing of the LMA removal on the incidence of respiratory
      adverse events over the whole emergence and postanaesthesia care unit phases.
      However, in the postanaesthesia care unit solely, awake removal was associated
      with significantly more respiratory adverse events than deep removal. TRIAL
      REGISTRATION NUMBER: ACTRN12609000387224 (www.anzctr.org.au).

PMID- 29452815
TI  - Variable versus conventional lung protective mechanical ventilation during open
      abdominal surgery (PROVAR): a randomised controlled trial.
AB  - BACKGROUND: Experimental studies showed that controlled variable ventilation
      (CVV) yielded better pulmonary function compared to non-variable ventilation
      (CNV) in injured lungs. We hypothesized that CVV improves intraoperative and
      postoperative respiratory function in patients undergoing open abdominal surgery.
      METHODS: Fifty patients planned for open abdominal surgery lasting >3 h were
      randomly assigned to receive either CVV or CNV. Mean tidal volumes and PEEP were
      set at 8 ml kg-1 (predicted body weight) and 5 cm H2O, respectively. In CVV,
      tidal volumes varied randomly, following a normal distribution, on a breath-by
      breath basis. The primary endpoint was the forced vital capacity (FVC) on
      postoperative Day 1. Secondary endpoints were oxygenation, non-aerated lung
      volume, distribution of ventilation, and pulmonary and extrapulmonary
      complications until postoperative Day 5. RESULTS: FVC did not differ
      significantly between CVV and CNV on postoperative Day 1, 61.5 (standard
      deviation 22.1) % vs 61.9 (23.6) %, respectively; mean [95% confidence interval
      (CI)] difference, -0.4 (-13.2-14.0), P=0.95. Intraoperatively, CVV did not result
      in improved respiratory function, haemodynamics, or redistribution of ventilation
      compared to CNV. Postoperatively, FVC, forced expiratory volume at the first
      second (FEV1), and FEV1/FVC deteriorated, while atelectasis volume and plasma
      levels of interleukin-6 and interleukin-8 increased, but values did not differ
      between groups. The incidence of postoperative pulmonary and extrapulmonary
      complications was comparable in CVV and CNV. CONCLUSIONS: In patients undergoing
      open abdominal surgery, CVV did not improve intraoperative and postoperative
      respiratory function compared with CNV. CLINICAL TRIAL REGISTRATION: NCT
      01683578.

PMID- 29452816
TI  - Transnasal humidified rapid insufflation ventilatory exchange for oxygenation of
      children during apnoea: a prospective randomised controlled trial.
AB  - BACKGROUND: Transnasal humidified rapid insufflation ventilatory exchange
      (THRIVE) comprises the administration of heated, humidified, and blended
      air/oxygen mixtures via nasal cannula at rates of >=2 litres kg-1 min-1. The aim
      of this randomized controlled study was to evaluate the length of the safe apnoea
      time using THRIVE with two different oxygen concentrations (100% vs 30% oxygen)
      compared with standard low-flow 100% oxygen administration. METHODS: Sixty
      patients, aged 1-6 yr, weighing 10-20 kg, undergoing general anaesthesia for
      elective surgery, were randomly allocated to receive one of the following oxygen
      administration methods during apnoea: 1) low-flow 100% oxygen at 0.2 litres kg-1
      min-1; 2) THRIVE 100% oxygen at 2 litres kg-1 min-1; and 3) THRIVE 30% oxygen at
      2 litres kg-1 min-1. Primary outcome was time to desaturation to 95%. Termination
      criteria included SpO2 decreased to 95%, transcutaneous CO2 increased to 65 mmHg,
      or apnoea time of 10 min. RESULTS: The median (interquartile range) [range]
      apnoea time was 6.9 (5.7-7.8) [2.8-10.0] min for low-flow 100% oxygen, 7.6 (6.2
      9.1) [5.2-10.0] min for THRIVE 100% oxygen, and 3.0 (2.4-3.7) [0.2-5.3] min for
      THRIVE 30% oxygen. No significant difference was detected between apnoea times
      with low-flow and THRIVE 100% oxygen administration (P=0.15). THRIVE with 30%
      oxygen demonstrated significantly shorter apnoea times (P<0.001) than both 100%
      oxygen modalities. The overall rate of transcutaneous CO2 increase was 0.57 (0.49
      0.63) [0.29-8.92] kPa min-1 without differences between the 3 groups (P=0.25).
      CONCLUSIONS: High-flow 100% oxygen (2 litres kg-1 min-1) administered via nasal
      cannulas did not extend the safe apnoea time for children weighing 10-20 kg
      compared with low-flow nasal cannula oxygen (0.2 litres kg-1 min-1). No
      ventilatory effect was observed with THRIVE at 2.0 litres kg-1 min-1. CLINICAL
      TRIAL REGISTRATION: NCT02979067.

PMID- 29452817
TI  - Drug errors in paediatric anaesthesia are common-but often unreported unless
      actual harm occurs.

PMID- 29452818
TI  - Medication errors in paediatric anaesthesia-a cultural change is urgently needed!

PMID- 29452819
TI  - Evidence of residual neuromuscular block with sugammadex vs neostigmine.

PMID- 29452820
TI  - Postoperative pulmonary complications and reversal agents.

PMID- 29452821
TI  - Do larger doses of neuromuscular blocking drugs increase postoperative morbidity?

PMID- 29452822
TI  - Evolution of observational research and implementation science in neuromuscular
      pharmacology to improve the value of care.

PMID- 29452823
TI  - Response to Murphy and Shelley.

PMID- 29452824
TI  - Monitoring rather than dose matters when using non-depolarising neuromuscular
      blocking agents.

PMID- 29452825
TI  - Reverse causation.

PMID- 29452826
TI  - Hyperoxia is a modifiable anaesthetic risk factor that varies in the practice of
      individual anaesthetists.

PMID- 29452827
TI  - Erratum to "Intraoperative permissive oliguria - how much is too much?" [Br J
      Anaesth 119 (2017) 1075-1077].

PMID- 29452829
TI  - Cribriform plate width is highly variable within and between subjects.
AB  - OBJECTIVE: All successful endonasal surgery, including functional endoscopic
      sinus surgery (FESS), depends on knowledge of both anatomy and the specific
      variations that can occur between and within patients. Familiarity with these
      structures is a critical component in preventing complications from these
      procedures, and failure to understand subtle variation can have disastrous
      results. The aim of this study was to characterize the anatomical variations (if
      any) of the cribriform plate using a large cadaveric sample set. Better
      understanding of the disparities within and between patients may have important
      implications for surgical planning. METHODS: Whole human skull specimens (31
      specimens, 62 sides) were examined to obtain dimensional measurements of the
      cribriform plate on the right and left sides. RESULTS: The average length of the
      cribriform plate was 21.28mm (range 15.25-27.73mm, SD 3.30mm). The average width
      of the cribriform plate (including the crista galli) was 4.53mm (range 1.75
      8.03mm, SD 1.20mm). When comparing side differences in individual specimens,
      there was more variability between widths, relative standard deviation 26.4%,
      than between lengths, relative standard deviation 15.5%. CONCLUSION: There is a
      range of both length and width of the cribriform plate, between and within
      individuals. This is particularly true for width. In practice, this emphasizes
      the importance of pre-operative imaging and recognition of anatomic variability
      for sinus or anterior skull base procedure.

PMID- 29452828
TI  - Glutamatergic Ventral Pallidal Neurons Modulate Activity of the Habenula
      Tegmental Circuitry and Constrain Reward Seeking.
AB  - BACKGROUND: The ability to appropriately integrate and respond to rewarding and
      aversive stimuli is essential for survival. The ventral pallidum (VP) plays a
      critical role in processing both rewarding and aversive stimuli. However, the VP
      is a heterogeneous structure, and how VP subpopulations integrate into larger
      reward networks to ultimately modulate these behaviors is not known. We identify
      a noncanonical population of glutamatergic VP neurons that play a unique role in
      responding to aversive stimuli and constraining inappropriate reward seeking.
      METHODS: Using neurochemical, genetic, and electrophysiological approaches, we
      characterized glutamatergic VP neurons (n = 4-8 mice/group). We performed patch
      clamp and in vivo electrophysiology recordings in the lateral habenula,
      rostromedial tegmental nucleus, and ventral tegmental area to determine the
      effect of glutamatergic VP neuron activation in these target regions (n = 6-10
      mice/group). Finally, we selectively optogenetically stimulated glutamatergic VP
      neurons in a real-time place preference task and ablated these neurons using a
      virally expressed caspase to determine their necessity for reward seeking.
      RESULTS: Glutamatergic VP neurons exhibit little overlap with cholinergic or
      gamma-aminobutyric acidergic markers, the canonical VP subtypes, and exhibit
      distinct membrane properties. Glutamatergic VP neurons innervate and increase
      firing activity of the lateral habenula, rostromedial tegmental nucleus, and
      gamma-aminobutyric acidergic ventral tegmental area neurons. While nonselective
      optogenetic stimulation of the VP induced a robust place preference, selective
      activation of glutamatergic VP neurons induced a place avoidance. Viral ablation
      of glutamatergic VP neurons increased reward responding and abolished taste
      aversion to sucrose. CONCLUSIONS: Glutamatergic VP neurons constitute a
      noncanonical subpopulation of VP neurons. These glutamatergic VP neurons increase
      activity of the lateral habenula, rostromedial tegmental nucleus, and gamma
      aminobutyric acidergic ventral tegmental area neurons and adaptively constrain
      reward seeking.

PMID- 29452830
TI  - Usefulness of reconstructed 3D images for cochlear implantation in a case with a
      facial nerve anomaly.
AB  - Facial nerve anomalies are a potential problem in patients with cochleovestibular
      malformations. A case of cochlear implant (CI) surgery in the presence of intra
      temporalbone facial nerve bifurcation is presented. During the first surgery, the
      facial nerve bifurcation obscured the promontory and round window. It was
      difficult to perform cochleostomy because of the lack of landmarks of the basal
      turn of the cochlea, and the first surgical attempt at cochleostomy was
      abandoned. A repeat CT scan was performed after the first surgery with
      reconstructed 3D images of the temporal bone and the cochlea, and then the
      cochlea was successfully opened at revision surgery. Reconstructed 3D CT images
      were very useful to identify the site of cochleostomy in this case with such
      difficult temporal bone anatomy.

PMID- 29452831
TI  - Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel
      Trenaunay Syndrome: A Case Report.
AB  - INTRODUCTION: Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular
      disorder characterized by a triad of cutaneous port wine capillary malformations,
      varicose veins, and hemihypertrophy of bone and soft tissues. AIMS: To report on
      a rare case of KTS in an adult man manifested by painless urethral bleeding
      during penile erection briefly review the clinical presentation and management of
      the genitourinary forms of this syndrome. METHODS: On presentation, the clinical
      features of this patient, including medical history, signs and symptoms, and
      imaging examinations, were recorded. After diagnosis and initial treatment, a
      literature review of the urethral features of KTS was performed and is discussed
      in this report. RESULTS: A 35-year-old man with KTS presented with painless
      urethral bleeding during penile erection that was associated with posterior
      urethral vascular malformations. The coagulation method was used to treat the
      malformation, and no urethral bleeding or gross hematuria occurred during a
      postoperative follow-up period of 6 months. CONCLUSION: This case demonstrates
      that coagulation therapy and careful follow-up can be adequate treatment
      approaches for urethral features of KTS. However, the long-term efficacy of
      coagulation for this disorder should be investigated further. Lei H, Guan X, Han
      H, et al. Painless Urethral Bleeding During Penile Erection in an Adult Man With
      Klippel-Trenaunay Syndrome: A Case Report. Sex Med 2018;6:180-183.

PMID- 29452832
TI  - Delayed endovascular aortic repair is associated with reduced in-hospital
      mortality in patients with blunt thoracic aortic injury.
AB  - OBJECTIVE: The traditional approach to stable blunt thoracic aortic injury (BTAI)
      endorsed by the Society for Vascular Surgery is early (<24 hours) thoracic
      endovascular aortic repair (TEVAR). Recently, some studies have shown improved
      mortality in stable BTAI patients repaired in a delayed manner (>=24 hours).
      However, the indications for use of delayed TEVAR for BTAI are not well
      characterized, and its overall impact on the patient's survival remains poorly
      understood. We sought to determine whether delayed TEVAR is associated with a
      decrease in mortality compared with early TEVAR in this population. METHODS: We
      conducted a retrospective cohort study of adult patients with BTAI (International
      Classification of Diseases, Ninth Revision diagnosis code 901.0) who underwent
      TEVAR (International Classification of Diseases, Ninth Revision procedure code
      39.73) from 2009 to 2013 using the National Sample Program data set. Missing
      physiologic data were imputed using chained multiple imputation. Patients were
      parsed into groups based on the timing of TEVAR (early, <24 hours, vs delayed,
      >=24 hours). The chi2, Mann-Whitney, and Fisher exact tests were used to compare
      baseline characteristics and outcomes of interest between groups. Multivariable
      logistic regression for mortality was performed that included all variables
      significant at P <= .2 in univariate analyses. RESULTS: A total of 2045 adult
      patients with BTAI were identified, of whom 534 (26%) underwent TEVAR. Patients
      with missing data on TEVAR timing were excluded (n = 27), leaving a total of 507
      patients for analysis (75% male; 69% white; median age, 40 years [interquartile
      range, 27-56 years]; median Injury Severity Score [ISS], 34 [interquartile range,
      26-41]). Of these, 378 patients underwent early TEVAR and 129 underwent delayed
      TEVAR. The two groups were similar with regard to age, sex, race, ISS, and
      presenting physiology. Mortality was 11.9% in the early TEVAR group vs 5.4% in
      the delayed group, with the early group displaying a higher odds of death (odds
      ratio, 2.36; 95% confidence interval, 1.03-5.36; P = .042). After adjustment for
      age, ISS, and admission physiology, the association between early TEVAR and
      mortality was preserved (adjusted odds ratio, 2.39; 95% confidence interval, 1.01
      5.67; P = .047). CONCLUSIONS: Consistent with current Society for Vascular
      Surgery recommendations, more BTAI patients underwent early TEVAR than delayed
      TEVAR during the study period. However, delayed TEVAR was associated with
      significantly reduced mortality in this population. Together, these findings
      support a need for critical appraisal and clarification of existing practice
      guidelines in management of BTAI. Future studies should seek to understand this
      survival disparity and to determine optimal selection of patients for early vs
      delayed TEVAR.

PMID- 29452833
TI  - Endothelial vascular cell adhesion molecule 1 is a marker for high-risk carotid
      plaques and target for ultrasound molecular imaging.
AB  - BACKGROUND: Molecular imaging of carotid plaque vulnerability to atheroembolic
      events is likely to lead to improvements in selection of patients for carotid
      endarterectomy (CEA). The aims of this study were to assess the relative value of
      endothelial inflammatory markers for this application and to develop molecular
      ultrasound contrast agents for their imaging. METHODS: Human CEA specimens were
      obtained prospectively from asymptomatic (30) and symptomatic (30) patients.
      Plaques were assessed by semiquantitative immunohistochemistry for vascular cell
      adhesion molecule 1 (VCAM-1), lectin-like oxidized low-density lipoprotein
      receptor 1, P-selectin, and von Willebrand factor. Established small peptide
      ligands to each of these targets were then synthesized and covalently conjugated
      to the surface of lipid-shelled microbubble ultrasound contrast agents, which
      were then evaluated in a flow chamber for binding kinetics to activated human
      aortic endothelial cells under variable shear conditions. RESULTS: Expression of
      VCAM-1 on the endothelium of CEA specimens from symptomatic patients was 2.4-fold
      greater than that from asymptomatic patients (P < .01). Expression was not
      significantly different between groups for P-selectin (P = .43), von Willebrand
      factor (P = .59), or lectin-like oxidized low-density lipoprotein receptor 1 (P =
      .99). Although most plaques from asymptomatic patients displayed low VCAM-1
      expression, approximately one in five expressed high VCAM-1 similar to plaques
      from symptomatic patients. In vitro flow chamber experiments demonstrated that
      VCAM-1-targeted microbubbles bind cells that express VCAM-1, even under high
      shear conditions that approximate those found in human carotid arteries, whereas
      binding efficiency was lower for the other agents. CONCLUSIONS: VCAM-1 displays
      significantly higher expression on high-risk (symptomatic) vs low-risk
      (asymptomatic) carotid plaques. Ultrasound contrast agents bearing ligands for
      VCAM-1 can sustain high-shear attachment and may be useful for identifying
      patients in whom more aggressive treatment is warranted.

PMID- 29452834
TI  - Pain and analgesic drugs in chronic venous ulcers with topical sevoflurane use.
AB  - OBJECTIVE: Pain in chronic venous ulcers (CVUs) notably increases with the usual
      cleaning of the wound. Chronic pain is usually poorly controlled even with the
      multiple analgesic treatments available. Analgesics can have different serious
      adverse effects and medical interactions in old patients with several
      comorbidities. This study reports the efficacy and safety of topical sevoflurane
      for treatment of pain in CVUs. METHODS: We report a descriptive and retrospective
      study of 30 patients older than 65 years with painful CVUs refractory to
      conventional analgesic treatments. Patients received topical sevoflurane
      treatment before the usual cleaning of the ulcer. Cleaning visits with
      sevoflurane every 2 days for a period of 1 month were scheduled. We compared the
      visual analog scale results and analgesic drugs for cleaning with and without
      topical sevoflurane. The systemic pharmacokinetics of sevoflurane after topical
      application has not been determined. RESULTS: Pain related to CVUs decreased with
      topical sevoflurane. Sevoflurane had an analgesic effect with latency time
      between 2 and 7 minutes. The duration of analgesia ranged between 8 and 18 hours.
      The time needed to take an analgesic treatment increased after application of
      sevoflurane. The use of other conventional analgesic drugs, including
      paracetamol, metamizole, nonsteroidal anti-inflammatory drugs, tramadol, and
      major opioids, was progressively reduced. The main local adverse effects were
      mild and transient, including heat, pruritus, and erythema. There were no
      systemic adverse effects. CONCLUSIONS: Topical sevoflurane has an intense, fast,
      and long-lasting local analgesic effect with an adequate safety profile. It also
      diminishes the taking of other conventional analgesic drugs. Topical sevoflurane
      is an efficient and safe therapeutic alternative for refractory painful CVUs.

PMID- 29452835
TI  - A comparison of preoperative and intraoperative vein mapping sizes for
      arteriovenous fistula creation.
AB  - BACKGROUND: Duplex ultrasound (DUS) mapping of the veins and arteries of the
      upper extremity is a well-established practice in arteriovenous fistula creation
      for long-term hemodialysis access. Previous publications have shown that vein
      diameters varying from 2 to 3 mm are predictive of success. Regional anesthesia
      is known to result in vasodilation and thus to increase the diameter of upper
      extremity veins. This study compares the sizes of veins measured by preoperative
      DUS mapping with those obtained after regional anesthesia to determine whether
      intraoperative DUS results in increased vein diameters and thus changes in the
      operative plan. A second goal was to determine whether such changes resulted in
      functional access. METHODS: This was a prospective observational study conducted
      between July 2013 and December 2014. Consecutive patients were preoperatively
      mapped and then intraoperatively mapped after administration of a regional
      anesthetic. Comparison of vein mapping sizes and comparison of preoperative plan
      and operative procedure based on the preoperative and intraoperative DUS mapping,
      respectively, were analyzed with a repeated-measures linear model. Significance
      testing was two sided, with a significance level of 5%. RESULTS: Sixty-five
      patients with end-stage renal disease underwent placement of arteriovenous access
      with preoperative and intraoperative DUS mapping after regional anesthesia.
      Comorbidities were representative of the vascular population. After regional
      anesthesia, intraoperative mid forearm and distal forearm cephalic veins were
      significantly larger than their respective preoperative measurements. Average
      increase in diameter of the mid forearm cephalic vein and distal forearm was 0.96
      mm (P < .001) and 0.50 mm (P = .04), respectively. There was a significant
      difference in the number and configuration of arteriovenous accesses (P < .0001).
      There was more than a twofold significant increase in radial artery-based access
      procedures concomitant with a significant reduction of brachial-based access
      procedures and a reduction in graft access procedures. Overall functional access
      rate was 63%, and patency rates were comparable to those reported in the
      literature. CONCLUSIONS: The routine use of intraoperative DUS mapping after
      regional anesthesia is recommended to determine the optimal access site for
      chronic hemodialysis access. Identifying additional access options not seen with
      physical examination and preoperative DUS mapping will provide end-stage renal
      disease patients with more fistula options and hence a longer access life span
      for a lifelong disease.

PMID- 29452836
TI  - Discussion.

PMID- 29452837
TI  - Dramatically Polarized Opinion on the Role of Brachytherapy Boost in Management
      of High-risk Prostate Cancer: A Survey of North American Genitourinary Expert
      Radiation Oncologists.
AB  - INTRODUCTION: Three randomized clinical trials have established brachytherapy
      (BT) boost in combination with external beam radiation therapy (EBRT) and
      androgen deprivation therapy (ADT) as superior to definitive EBRT and ADT alone
      in terms of biochemical control (but not overall survival) at the expense of
      increased toxicity in men with high-risk (HR) prostate cancer (PCa). The current
      view regarding these 2 treatment algorithms among North American genitourinary
      (GU) experts is not known. METHODS: A survey was distributed to 88 practicing
      North American GU physicians serving on decision-making committees of cooperative
      group research organizations. Questions pertained to opinions regarding BT as
      monotherapy for low-risk PCa and BT boost for HR PCa. Responders were asked to
      self-identify as BT experts versus non-experts. Treatment recommendations were
      correlated with practice patterns using the Fisher exact test. RESULTS: Forty-two
      radiation oncologists completed the survey, of whom 23 (55%) recommend EBRT and
      ADT alone and 19 (45%) recommend addition of BT boost. Twenty-five participants
      (60%) identified themselves as BT experts. Nearly 90% of those recommending BT
      boost were BT experts versus approximately 10% of non-BT experts (P < .001).
      Responders who recommended BT monotherapy as first-choice treatment for low-risk
      PCa were more likely to recommend BT boost for HR PCa (P < .0001). CONCLUSIONS:
      There is a dramatic polarization in opinions regarding incorporation of BT boost
      into EBRT + ADT therapy for patients with HR PCa among North American GU
      radiation oncology experts, who serve on decision-making committees and influence
      the national treatment guidelines and future clinical trials. Those who identify
      themselves as BT experts are significantly more likely to recommend BT boost.
      These findings are likely to influence the national guidelines and implementation
      of BT boost in current and future North American PCa clinical studies.

PMID- 29452838
TI  - External quality control program in screening for infectious diseases at blood
      banks in Mexico.
AB  - INTRODUCTION: Quality control for the detection of infectious markers in blood
      banks is a necessary activity to ensure the accuracy of donor screening results.
      Considering that in Mexico blood safety is one of the goals of the National
      Action Programs, it is essential to evaluate banks through an External Quality
      Control Program. OBJECTIVE: To analyze one of the evaluations that showed the
      greatest participation (2014-2/lot46) of banks in the Mexican Republic in the
      detection of transfusion-transmitted diseases. MATERIALS AND METHODS: A
      randomized panel of infectious markers of HIV, HCV, HBV, Treponema pallidum and
      Trypanosoma cruzi was manufactured under high quality standards. The evaluation
      criteria for each infectious marker were the identification of false positives
      and false negative results. Additionally, technologies used to detect infectious
      markers were requested for each bank. RESULTS: Of the 503 banks, only 374
      participated in the evaluation. Technologies based on chemiluminescence,
      immunofluorescence and immunocolorimetry were used to detect viral markers. Even
      rapid tests for T. pallidum continue to be the methods of choice with 42%.
      Trypanosoma cruzi was 20% with fast techniques versus 80% with automated tests.
      Highest incidence of false positives was identified for T. pallidum and HBV,
      followed by T. cruzi, HIV and HCV. Fourteen (3.74%) false negatives results were
      identified for T. cruzi, followed by T. pallidum (n = 5/1.33%), HCV (n = 4/1.06)
      and HVB/HIV (n = 2/0.53%). CONCLUSION: False positive results identified for each
      infectious marker was considered high. This evidence will allow us to focus on
      areas of opportunity during serologic screening with greater emphasis on good
      laboratory practices.

PMID- 29452839
TI  - Development of selective inhibitors for the treatment of rheumatoid arthritis:
      (R)-3-(3-(Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3
      oxopropanenitrile as a JAK1-selective inhibitor.
AB  - A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for
      JAK1-selective inhibitors through the modification of tofacitinib's core
      structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we
      selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a
      scaffold for further SAR studies. From biochemical enzyme assays and liver
      microsomal stability tests, (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4
      yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile (6) was chosen for further in vivo
      test through oral administration. Compound 6 showed improved selectivity for JAK1
      compared to that of tofacitinib (IC50 11, 2.4 * 102, 2.8 * 103, and 1.1 * 102 nM
      for JAK1, JAK2, JAK3, and TYK2, respectively). In CIA and AIA model tests,
      compound 6 exhibited similar efficacy to tofacitinib citrate.

PMID- 29452840
TI  - Borrelidins F-I, cytotoxic and cell migration inhibiting agents from mangrove
      derived Streptomyces rochei SCSIO ZJ89.
AB  - Borrelidin A (1) is produced by several species of Streptomyces and within its
      bioactive scaffold, the vinylic nitrile moiety is essential for activity. We
      report herein newly discovered members of the borrelidin family, borrelidin F
      (2), borrelidin G (3), borrelidin H (4) and borrelidin I (5); all were isolated
      from Streptomyces rochei SCSIO ZJ89 originating from a mangrove-derived sediment
      sample. These structurally diverse metabolites enabled a number of new structure
      activity relationships (SARs) to be identified, especially with respect to the
      different configurations at the C11-OH and C12-C15 double bonds for which the
      absolute configurations were determined using spectroscopic methods. Importantly,
      borrelidin H (4) was found to have a therapeutic window superior to that of
      borrelidin A (1) in vitro and could inhibit migration of cancer cells.

PMID- 29452841
TI  - Impact of age following treatment of severely calcified coronary lesions with the
      orbital atherectomy system: 3-year follow-up.
AB  - OBJECTIVES: We investigated the safety and efficacy of coronary orbital
      atherectomy to treat severely calcified lesions prior to stenting based upon age.
      BACKGROUND: The ORBIT II study reported the safety and efficacy with orbital
      atherectomy in 443 patients with severely calcified lesions. Elderly patients
      undergoing percutaneous coronary intervention may be at increased risk for major
      adverse cardiac events (MACE) and death compared with younger patients. METHODS:
      Patients were stratified according to age (>=75 year old [174/443, 39.3%] vs. <75
      year old [269/443, 60.7%]). The MACE rate, defined as cardiac death, myocardial
      infarction (CK-MB > 3X ULN), and target vessel revascularization, was examined at
      30-day and 3-year follow-up. RESULTS: Elderly and non-elderly groups had similar
      rates of procedural (87.9% vs. 89.5%, p = 0.64) and angiographic success (91.4%
      vs. 91.4%, p = 1.00). Severe angiographic complications were also similar in both
      groups (6.9% vs. 7.4%, p = 1.00). There was no statistically significant
      difference in MACE rates in the elderly and younger groups at 30 days (10.9% vs.
      10.1%; p = 0.76) and 3 years (27.8% vs. 20.7%, p = 0.13). The individual
      endpoints of cardiac death (9.1% vs. 5.1%, p = 0.14), myocardial infarction
      (13.4% vs. 9.7%, p = 0.27), and target vessel revascularization (10.6% vs. 10.0%,
      p = 0.91) were also similar in both groups at 3 years. CONCLUSIONS: The rates of
      adverse clinical events in elderly patients who underwent orbital atherectomy
      were low and similar to the non-elderly patients, suggesting that it could be a
      reasonable treatment strategy for elderly patients with severely calcified
      lesions.

PMID- 29452842
TI  - Total wrist access for angiography and interventions: Procedural success and
      access site crossover in a high volume transradial center.

PMID- 29452843
TI  - Ticagrelor versus clopidogrel in East Asian patients with acute coronary
      syndrome: Systematic review and meta-analysis.
AB  - BACKGROUND: Bleeding complications are associated with unfavorable outcomes in
      patients with acute coronary syndrome (ACS). Compared to Whites, several studies
      demonstrated a higher risk of bleeding in Asians who present with acute
      myocardial infarction. To date, the efficacy and safety of ticagrelor in East
      Asian population have not been well established. METHODS: We conducted a
      systematic review and meta-analysis of randomized controlled trials that compared
      ticagrelor and clopidogrel in East Asian patients with acute coronary syndrome
      (ACS). We systematically searched MEDLINE, EMBASE, the Cochrane Central Register
      of Controlled Trials, and ClinicalTrial.gov database. RESULTS: Three randomized
      controlled trials, including a total of 1552 patients, met our inclusion
      criteria. Study countries included Japan, South Korea, and China. All studies
      defined primary efficacy endpoint and major bleeding events in accordance with
      the PLATO definition. Ticagrelor was associated with a numerically lower, albeit
      statistically nonsignificant, risk of primary efficacy endpoint defined as a
      composite of death from vascular causes, myocardial infarction, or stroke (odds
      ratio 0.84; 95% confidence interval 0.43-1.63; p = 0.60). Ticagrelor was
      associated with a significantly higher risk of PLATO-defined major bleeding
      compared to clopidogrel (odds ratio 1.52; 95% confidence interval 1.04-2.23; p =
      0.03). CONCLUSIONS: Our meta-analysis demonstrated that ticagrelor was associated
      with a higher risk of major bleeding compared to clopidogrel in East Asian
      patients with ACS. Further studies evaluating the role of ticagrelor in
      management of ACS in East Asian patients are warranted.

PMID- 29452844
TI  - Fungal effectors at the crossroads of phytohormone signaling.
AB  - Phytohormone networks are crucial for maintaining the delicate balance between
      growth and biotic stress responses in plants. Jasmonic acid, salicylic acid,
      ethylene, and the associated signaling crosstalk are important for pathogen
      defense; whereas gibberellin and cytokinin function in growth and development in
      plants. Plant pathogenic fungi have evolved remarkable strategies to manipulate
      and/or hijack such phytohormone signaling cascades for their own benefit, thus
      leading to susceptibility and disease in host plants. Interestingly, these
      hormones are also targeted by fungal endosymbionts and mutualists during
      beneficial interactions with plants. We highlight current advances in our
      understanding of the role of fungal effectors in such antagonistic manipulation
      of phytohormones during pathogenic as well as symbiotic association with plant
      hosts. In addition to the aforementioned effector-based control, certain
      phytohormone mimics have recently emerged as a powerful molecular language in
      fungal manipulation of defense responses and innate immunity in plants.

PMID- 29452845
TI  - Just the surface: advances in the discovery and characterization of necrotrophic
      wheat effectors.
AB  - For many years pathogens of wheat have remained poorly understood. Hindered by an
      inaccessible host and the obligate nature of many of the pathogens, our
      understanding of these interactions has been limited compared to other more
      amenable pathosystems. However, breakthroughs over recent years have shed new
      light on diseases of wheat, particularly those caused by the genetically
      tractable necrotrophic pathogens. We now understand that many of the necrotrophic
      fungal pathogens do interact with wheat in a strict gene-for-gene relationship,
      and that pathogen and host partners in these interactions have now been
      identified. This improved understanding of necrotrophic effector biology has
      fundamentally changed the way we consider these important wheat diseases.

PMID- 29452846
TI  - Differential role of gpaB and sidA gene expressions in relation to virulence in
      Aspergillus species from patients with invasive aspergillosis.
AB  - The virulence genes in invasive aspergillosis (IA) have not been analyzed
      adequately. The present study was designed to evaluate the expression of gpaB and
      sidA genes, which are important virulence genes in Aspergillus spp. from
      bronchoalveolar lavage (BAL) samples. Direct examination and culture on Czapek
      Agar and Sabouraud Dextrose Agar media were performed for 600 BAL specimens
      isolated from patients with possible aspergillosis. A Galactomannan ELISA assay
      was also carried out. The expression levels of the gpaB and sidA genes in
      isolates were analyzed using quantitative real-time PCR (qRT-PCR). We identified
      2 species, including Aspergillus flavus (A. flavus) and Aspergillus fumigatus (A.
      fumigatus) in 25 positive samples for invasive aspergillosis as validated using
      GM-ELISA. A. flavus is the main pathogen threatening transplant recipients and
      cancer patients worldwide. In this study, A. flavus had low levels of the gpaB
      gene expression compared to A. fumigatus (p=0.006). The highest sidA expression
      was detected in transplant recipients (p=0.05). There was no significant
      correlation between sidA expression and underlying disease (p=0.15). The sidA and
      gpaB gene expression patterns may provide evidence that these virulence genes
      play important roles in the pathogenicity of Aspergillus isolates; however, there
      are several regulatory genes responsible for the unexpressed sidA and gpaB genes
      in the isolates.

PMID- 29452847
TI  - Primary antibiotic resistance and its relationship with cagA and vacA genes in
      Helicobacter pylori isolates from Algerian patients.
AB  - The epidemiology of Helicobacter pylori resistance to antibiotics is poorly
      documented in Africa and especially in Algeria. The aim of our study was to
      determine the antibiotic resistance rates, as well as its possible relationship
      with VacA and CagA virulence markers of isolates from Algerian patients. One
      hundred and fifty one H. pylori isolate were obtained between 2012 and 2015 from
      200 patients with upper abdominal pain. Antimicrobial susceptibility testing was
      performed for amoxicillin, clarithromycin, metronidazole, ciprofloxacin,
      rifampicin and tetracycline. Molecular identification of H. pylori and the
      detection of vacA and cagA genes were performed using specific primers. We found
      that H. pylori was present in 83.5% of collected biopsies, 54.9% of the samples
      were cagA positive, 49.67% were vacA s1m1, 18.30% were vacA s1m2 and 25.49% were
      vacA s2m2. Isolates were characterized by no resistance to amoxicillin (0%),
      tetracycline (0%), rifampicin (0%), a high rate of resistance to metronidazole
      (61.1%) and a lower rate of resistance to clarithromycin (22.8%) and
      ciprofloxacin (16.8%). No statically significant relationship was found between
      vagA and cagA genotypes and antibiotic resistance results (p>0.5) except for the
      metronidazole, which had relation with the presence of cagA genotype (p=0.001).

PMID- 29452848
TI  - Optimization of liquid fermentation conditions for biotransformation zein by
      Cordyceps militaris 202 and characterization of physicochemical and functional
      properties of fermentative hydrolysates.
AB  - Cordyceps militaris 202 is a potential fungus for biotransformation zein, due to
      its various proteases, high tolerance and viability in nature. In this article,
      single factor experiment and response surface methodology were applied to
      optimize the liquid fermentation conditions and improve the ability of
      biotransformation zein. The optimized fermentation conditions were as follows:
      inoculum concentration of 19%, volume of liquor of 130mL/500mL and pH of 4.7.
      Under this condition, the degree of hydrolysis (DH) was 27.31%. The zein
      hydrolysates from fungi fermentation maintained a high thermal stability.
      Compared to the original zein, the zein hydrolysates were found to have high
      solubility, which most likely results in improved foaming and emulsifying
      properties. Overall, this research demonstrates that hydrolysis of zein by C.
      militaris 202 is a potential method for improving the functional properties of
      zein, and the zein hydrolysates can be used as functional ingredients with an
      increased antioxidant effect in both food and non-food applications.

PMID- 29452849
TI  - Bacterial communities in mining soils and surrounding areas under regeneration
      process in a former ore mine.
AB  - Human activities on the Earth's surface change the landscape of natural
      ecosystems. Mining practices are one of the most severe human activities,
      drastically altering the chemical, physical and biological properties of the soil
      environment. Bacterial communities in soil play an important role in the
      maintenance of ecological relationships. This work shows bacterial diversity,
      metabolic repertoire and physiological behavior in five ecosystems samples with
      different levels of impact. These ecosystems belong to a historical area in Iron
      Quadrangle, Minas Gerais, Brazil, which suffered mining activities until its
      total depletion without recovery since today. The results revealed Proteobacteria
      as the most predominant phylum followed by Acidobacteria, Verrucomicrobia,
      Planctomycetes, and Bacteroidetes. Soils that have not undergone anthropological
      actions exhibit an increase ability to degrade carbon sources. The richest soil
      with the high diversity was found in ecosystems that have suffered anthropogenic
      action. Our study shows profile of diversity inferring metabolic profile, which
      may elucidate the mechanisms underlying changes in community structure in situ
      mining sites in Brazil. Our data comes from contributing to know the bacterial
      diversity, relationship between these bacteria and can explore strategies for
      natural bioremediation in mining areas or adjacent areas under regeneration
      process in iron mining areas.

PMID- 29452850
TI  - Evaluation of dot-blot test for serological diagnosis of bovine brucellosis.
AB  - The objective of this study was to standardize and validate the dot-blot test for
      the serological diagnosis of bovine brucellosis, compare the results with those
      found in the 2-mercaptoethanol (2-ME) and complement fixation test (CF), and
      estimate the relative sensitivity and specificity of the dot-blot compared to
      these tests. Fifty bovine blood serum samples were used for the test
      standardization, and 1315 samples were used for evaluation and comparison between
      the tests; the results were compared using the Kappa indicator. At the end of
      standardization, it was established as optimal for the antigen obtained from
      Brucella abortus B19 after passing through a microorganism rupture process, the
      blood serum samples diluted at 1:100, and the conjugate at 1:30,000. The
      comparison of the dot-blot results with 2-ME showed Kappa index of 0.9939,
      sensitivity of 99.48%, and specificity 99.91%, with CF, Kappa index of 0.8226,
      sensitivity 100% and specificity 95.32%. Using the combination of the test
      results 2-ME and CF to establish the true condition of the animal, the dot-blot
      showed relative sensitivity of 100%, and relative specificity of 99.91%. The
      evaluated test proved to be effective and reliable, besides being easy to handle
      and interpret the results.

PMID- 29452851
TI  - Elastin increases biofilm and extracellular matrix production of Aspergillus
      fumigatus.
AB  - Aspergillus fumigatus is an opportunistic saprobe fungus that accounts for 90% of
      cases of pulmonary aspergillosis in immunosuppressed patients and is known for
      its angiotropism. When it reaches the respiratory tract, A. fumigatus interacts
      with structural components and blood vessels of the lungs, such as elastin. To
      understand the effect of this structural component, we examined the effect of
      elastin on the production and development of the biofilm of A. fumigatus. In RPMI
      containing 10mg/mL of elastin, a significant increase (absorbance p<0.0001; dry
      weight p<0.0001) in the production of biofilm was observed in comparison to when
      RPMI was used alone, reaching a maximum growth of 18.8mg (dry weight) of biofilm
      in 72h. In addition, elastin stimulates the production (p=0.0042) of
      extracellular matrix (ECM) and decreases (p=0.005) the hydrophobicity during the
      development of the biofilm. These results suggest that elastin plays an important
      role in the growth of A. fumigatus and that it participates in the formation of
      thick biofilm.

PMID- 29452852
TI  - Reduction of patient radiation dose with a new organ based dose modulation
      technique for thoraco-abdominopelvic computed tomography (CT) (Liver dose right
      index).
AB  - PURPOSE: To evaluate the radiation dose reduction, image quality and diagnostic
      confidence with thoraco-abdominopelvic computed tomography (TACT) using a new
      organ based dose modulation system (liver dose right index [Liver DRI]), compared
      to TACT using a standard automatic exposure control adjusting mA according to
      attenuation. METHODS: A total of 37 patients who had two TACT examinations on 2
      different CT scanners, one using standard automatic exposure control (combination
      of a DoseRight automatic current selection and Z modulation) and one using Liver
      DRI were included. There were 19 men and 18 women with a mean age of 67.6+/-11.7
      (SD) years (range: 36-85 years) For each patient, volume CT dose index (CTDIvol),
      size-specific dose estimates (SSDE) and signal-to-noise ratio (SNR) were
      evaluated at each anatomic level (lung, breast, liver and pelvis area) for each
      protocol. Two radiologists assessed independently image quality, artifacts and
      diagnostic confidence. RESULTS: The radiation dose decreased significantly using
      Liver DRI compared to standard automatic exposure control on the total scan
      length, lung, breast and pelvis area, with a significant CTDIvol reduction of 27%
      (P=0.0001), 23% (P=0.0002), 24% (P=0.0002) and 31% (P=0.0001), respectively; and
      a significant SSDE reduction of 23% (P=0.0001), 28% (P=0.0001), 23% (P=0.0002)
      and 29% (P=0.0001), respectively. No significant SNR reductions were observed in
      all measured tissues at the level of the aortic arch, celiac trunk and iliac
      bifurcation, except in the muscle (P=0.0013) and fat tissue (P=0.0052) at the
      level of the ureteral meatus. No significant differences were noted between both
      protocols in overall image quality, artifacts and diagnostic confidence with an
      excellent inter observer agreement between radiologists (Kappa values of 0.83,
      0.85 and 0.88, respectively). CONCLUSION: Liver DRI organ based dose modulation
      technique allows significant dose reduction compared to standard automatic
      exposure control while preserving diagnostic image quality in all thoraco
      abdominopelvic areas.

PMID- 29452853
TI  - The impact of sex steroid agonists and antagonists on folliculogenesis in the
      neonatal porcine ovary via cell proliferation and apoptosis.
AB  - The objective of the study was to examine the effects of androgen and estrogen
      agonists or antagonists on the follicle formation, ovarian cell proliferation and
      apoptosis as well as plasma steroid concentration in neonatal pigs. Piglets were
      injected with testosterone propionate (TP, 20 mg/kg bw), flutamide (FLU, 50 mg/kg
      bw), 4-tert-octylphenol (OP, 100 mg/kg bw), ICI 182,780 (ICI, 400 MUg/kg bw),
      methoxychlor (MXC, 100 mg/kg bw) or corn oil (CTR, controls) between postnatal
      Days 1 and 10 (n = 4/group). Heart blood was collected and ovaries were excised
      from the 11-day-old piglets. The lower percentage of oocytes within an egg nest
      and higher ovarian expression of active caspase 3 were found in TP (androgen
      excess) piglets compared to controls. FLU-induced androgen deficiency decreased
      the percentage of primordial follicles, increased that of early primary follicles
      and diminished ovarian cell proliferation. OP-induced estrogen action increased
      the percentage of primordial and developing follicles as well as cell
      proliferation. ICI-induced estrogen deficiency decreased the percentage of
      transitional follicles and ovarian cell proliferation, while increased the
      percentage of primordial follicles and the abundance of active caspase 3.
      Treatment with MXC, exhibiting estrogenic, antiestrogenic, and antiandrogenic
      activities, declined the percentage of developing follicles and cell
      proliferation. Moreover, the investigated compounds differentially affected
      plasma steroid level. In conclusion, the present study demonstrated clear effects
      of TP and FLU during the earliest stages of folliculogenesis in pigs (nest
      breakdown and follicle assembly), whereas OP and ICI influenced also the
      subsequent stages of follicle initial recruitment and growth. Therefore, the
      androgen and estrogen seems to be important for the follicle assembly and
      follicle growth in neonatal porcine ovaries.

PMID- 29452854
TI  - Assessment of the temperature cut-off point by a commercial intravaginal device
      to predict parturition in Piedmontese beef cows.
AB  - Dystocic parturitions have an adverse impact on animal productivity and therefore
      the profitability of the farm. In this regard, accurate prediction of calving is
      essential since it allows for efficient and prompt assistance of the dam and the
      calf. Numerous approaches to predict parturition have been studied, among these,
      measurement of intravaginal temperature (IVT) is the most effective method at the
      field level. Thus, objectives of this experiment were, 1) to find an IVT cut-off
      to predict calving within 24 h, and 2) to clarify the use of IVT as an automated
      method of calving detection in housed beef cows. A commercial intravaginal
      electronic device (Medria Vel'Phone(r)) with a sensor that measures the IVT every
      12 h was used. Piedmontese cows (n = 211; 27 primiparous and 184 multiparous)
      were included in this study. One-way analysis of variance was used to assess the
      temperature differences at 0, 12, 24, 36, 48 and 60 h before parturition.
      Receiving operator characteristic curves were built to determine the temperature
      cut-off which predicts calving within 24 h with the highest summation of
      sensitivity (Se) and specificity (Sp). Binomial logistic regression models were
      computed to identify factors that may affect the IVT before calving. Mean
      gestation length was 291.5 +/- 13.7 d (primiparous, 292 +/- 14.1 d; multiparous,
      289 +/- 9.2 d). A decrease (P < 0.001) in the average IVT was found from 60 h
      before calving until the expulsion of the IVT device. A significant (P < 0.05)
      reduction in the IVT was noticeable from 24 h before until parturition. The IVT
      drop to predict parturition 24 h before calving was 0.21  degrees C (area under
      the curve [AUC] = 0.72; Se = 66%, Sp = 76%). Furthermore, the IVT cut-off value
      to predict parturition within 24 h was 38.2  degrees C (AUC = 0.89; Se = 86%, Sp
      = 91%). None of the evaluated fixed effects (parity, dystocia, season or length
      of gestation) affected (P ? 0.05) the IVT variation from 60 h before and up to
      calving. To conclude, the IVT average seems to be a better parameter than the
      drop in temperature to predict parturition within 24 h. In this regard, a cut-off
      of 38.2  degrees C showed a high Se and Sp for predicting calving. This study
      demonstrates the usefulness of a commercially available device to predict calving
      to improve management in stabled beef farms.

PMID- 29452855
TI  - Constituents of neutrophil extracellular traps induce in vitro collagen formation
      in mare endometrium.
AB  - Neutrophil extracellular traps (NETs) are DNA complexes carrying nuclear and
      cytoplasmic proteins, such as elastase (ELA), cathepsin-G (CAT) and
      myeloperoxidase (MPO). Mare endometrosis is a chronic degenerative process
      characterized by excessive collagen in endometrium. While NETs fight bacteria
      that cause endometritis, they may trigger endometrial fibrogenesis. The aim was
      to evaluate the in vitro effect of some NETs components on mare endometrial
      fibrogenesis and determine its relationship with histopathology or estrous cycle.
      Endometrial explants were incubated with NETs components (ELA, CAT, MPO or
      oxytocin). Collagen type I (COL1) protein and type I and III (COL3) gene
      transcription were evaluated in follicular and mid-luteal phases endometria
      (Kenney and Doig type I/IIA and IIB/III). Increased COL1 occurred with all NETs
      proteins, although endometrial response to each NETs protease depended on estrous
      cycle and/or endometrial category. Since ELA enhanced COL1 production, NETs
      persistence might be linked to endometrosis. Estrous cycle influenced COL1
      protein concentration and COL3 transcripts, suggesting that follicular phase may
      favor endometrial collagen production. However, luteal phase endometria with
      moderate or severe lesions may be also susceptible to fibrotic effects of NETs
      constituents. These data propose that NETs involvement in chronic endometritis in
      mares may act as putative endometrial fibrogenic mediators.

PMID- 29452856
TI  - Generalized cardiovascular disease on a preoperative CT scan is predictive for
      anastomotic leakage after esophagectomy.
AB  - BACKGROUND: Recent studies demonstrated that calcification of arteries supplying
      the gastric tube is associated with anastomotic leakage after esophagectomy.
      However, it remains unclear whether this association only derives from local flow
      limitations, or generalized vascular disease as well. The purpose of this study
      was to determine whether calcification throughout the entire cardiovascular
      system is associated with anastomotic leakage. METHODS: Consecutive patients who
      underwent an esophagectomy with gastric tube reconstruction and cervical
      anastomosis for esophageal cancer were analyzed. Diagnostic CT images were scored
      for the presence of arterial calcification on 10 locations based on a visual
      grading system. The association with anastomotic leakage was studied using
      logistic regression analysis. RESULTS: A total of 406 patients were included for
      analysis of whom 104 developed anastomotic leakage (25.6%). Presence of
      calcification in the coronary arteries (minor calcification: 36.5% leakage; no
      calcification: 18.1%, p = .001), supra-aortic arteries (minor calcification:
      30.9% leakage; major calcification: 35.3%; no calcification: 16.1%, p = .007 and
      p < .001, respectively) and thoracic aorta (major calcification: 33.3% leakage;
      no calcification: 19.4%, p = .011) was associated with leakage. In multivariable
      analysis, minor calcification of the coronary arteries (OR 2.29, 95% CI: 1.28
      4.12, p = .005) and calcification of the supra-aortic arteries (OR 2.48, 95% CI:
      1.30-4.74, p = .006 for minor calcification and OR 2.72, 95% CI: 1.49-4.99, p =
      .001 for major calcification) remained independently associated with leakage.
      CONCLUSIONS: Calcification of the coronary and supra-aortic arteries on routine
      CT are predictive of cervical anastomotic leakage after esophagectomy. These
      results suggest that generalized cardiovascular disease is a strong indicator for
      the risk of leakage.

PMID- 29452857
TI  - Impact of the off-clamp endoscopic robot-assisted simple enucleation (ERASE) of
      clinical T1 renal tumors on the postoperative renal function: Results from a
      matched-pair comparison.
AB  - PURPOSE: To evaluate the surgical and functional outcomes of a matched-paired
      series of on-clamp vs off-clamp endoscopic robot-assisted simple enucleation
      (ERASE) and standardized renorraphy in a tertiary referral institution, to search
      for predictors of functional drop after surgery and to investigate the influence
      of off-clamp technique in patients presenting these characteristics. MATERIALS
      AND METHODS: A matched-pair comparison of 120 on-clamp vs 120 off-clamp over 491
      patients treated with ERASE was performed. Perioperative and functional outcomes
      were compared between groups. RESULTS: Patients treated with on-clamp and off
      clamp technique had comparable complication and positive surgical margin rate.
      The off-clamp group had a significantly lower eGFR drop compared to the on-clamp
      group at 3rd postoperative day (POD) (1% vs 7%, p = 0.0001) and at 30th POD (2.5%
      vs 9%, p = 0.01) from baseline. This difference lost its statistical significance
      at 6th month and at last follow-up (median 40 months). At multivariable analysis
      the Charlson comorbidity index (OR 2.06, p < 0.0001), uncontrolled type 2
      diabetes mellitus (OR 4.13, p < 0.001) were independent predictive factors of a
      >15% eGFR drop from baseline to last follow-up. In a subanalysis over 64 comorbid
      patients, those patients who underwent off-clamp ERASE had a significantly lower
      eGFR drop compared to the comorbid counterpart during the whole follow-up.
      CONCLUSIONS: The off-clamp ERASE is a safe surgical technique with a
      significantly lower renal function drop compared to on-clamp ERASE in the early
      perioperative time. Patients with comorbidity might represent a subgroup of
      patients having a functional benefit after off-clamp RAPN even in the long-term
      period.

PMID- 29452858
TI  - The effect of being informed on receiving immediate breast reconstruction in
      breast cancer patients.
AB  - INTRODUCTION: In previous research from the NABON breast cancer audit, observed
      hospital variation in immediate breast reconstruction (IBR) rates in the
      Netherlands could not be fully explained by tumour, patient, and hospital
      factors. The process of information provision and decision-making may also
      contribute to the observed variation; the objective of the current study was to
      give insight in the underlying decision-making process for IBR and to determine
      the effect of being informed about IBR on receiving IBR. METHODS: A total of 502
      patients with IBR and 716 without IBR treated at twenty-nine hospitals were
      invited to complete an online questionnaire on obtained information and decision
      making regarding IBR. The effect of being informed about IBR on receiving IBR was
      determined by logistic regression analysis. RESULTS: Responses from five hundred
      and ten patients (n = 229 IBR, n = 281 without IBR) were analysed. Patients with
      IBR compared to patients without reconstruction showed a difference in patient,
      tumour, treatment (including radiotherapy), and hospital characteristics.
      Patients with IBR were more often informed about IBR as a treatment option (99%
      vs 73%), they discussed (dis)advantages more often with their physician (86% vs
      68%), and they were more often involved in shared decision-making (91% vs 67%)
      compared to patients without IBR. Multivariate logistic regression analysis,
      corrected for confounders, showed that being informed about IBR increased the
      odds for receiving IBR fourteen times (p < 0.001). CONCLUSIONS: The positive
      effect of being informed about IBR on receiving IBR stresses the importance of
      treatment information in the decision-making process for IBR.

PMID- 29452859
TI  - Evaluation of liquid biopsies for detection of emerging mutated genes in
      metastatic colorectal cancer.
AB  - BACKGROUND: Detection of gene mutations is important for planning molecular
      targeted therapy. Although most gene mutations are concordant between primary
      colon cancers and their liver metastases, new mutations can emerge in metastases.
      The liquid biopsy is a newly developed, gene analytic method to detect mutations
      in metastatic tumors. In this prospective study, we evaluated the applicability
      of liquid biopsies in the detection of mutations in primary and metastatic
      tumors. METHODS: We included 22 patients with liver metastases from colorectal
      cancer and extracted DNA from primary colorectal tumors, metastatic liver tumors,
      and peripheral blood (liquid biopsy). Next-generation sequencing (NGS) and
      digital PCR were performed to detect mutations in these three sample types.
      RESULTS: We found a total of 36 different mutations in samples from primary
      tumors, liver metastases, and liquid biopsies using NGS. Twenty-eight of these
      mutations were found in all three types of samples, whereas liquid biopsy did not
      identify four mutations that had been found in both primary tumors and liver
      metastases, but did identify four mutations that were found in liver tumors but
      not in primary tumors. The sensitivity of liquid biopsies for detecting mutations
      in liver metastases was 64% (23/36) using NGS and 89% (32/36, P = 0.02) using
      dPCR. The specificities of NGS and dPCR were 100% (23/23) and 100% (32/32),
      respectively. CONCLUSIONS: Emerging mutations, which are not found in primary
      tumors, can be detected in their metastases and liquid biopsies.

PMID- 29452861
TI  - Corrigendum to "Thapsigargin triggers cardiac contractile dysfunction via NADPH
      oxidase-mediated mitochondrial dysfunction: Role of Akt dephosphorylation" [Free
      Radic. Biol. Med. 51(12) (2011) 2172-2184].

PMID- 29452860
TI  - Pancreaticoduodenectomy in the surgical management of primary retroperitoneal
      sarcoma.
AB  - BACKGROUND: In retroperitoneal sarcoma (RPS), the optimal extent of resection
      must balance adequate disease control with potential for morbidity. We sought to
      study the frequency and outcomes after a Whipple procedure or
      pancreaticoduodenectomy (PD) in patients undergoing resection for primary RPS.
      METHODS: Participating referral centers within the Trans-Atlantic Retroperitoneal
      Sarcoma Working Group provided retrospective data from January 2007 to December
      2016 for patients with primary RPS who underwent PD along with the total number
      of consecutive resections done during the same time period. Data from
      participating centers were combined for analysis. RESULTS: In total, 29 patients
      underwent PD among 2068 resections performed for primary RPS (1.4%). The
      predominant histologic subtypes were liposarcoma and leiomyosarcoma. All PD
      patients underwent concomitant resection of additional organs (median: 2, range:
      1-5), including 13 patients (45%) who also received vena cava resection.
      Definitive evidence of microscopic invasion of the duodenum or pancreas was seen
      in 84% of patients. Postoperatively, 10 patients (34%) had major complications
      including 8 (28%) that developed a clinically-significant pancreatic leak. One
      postoperative death (3.4%) occurred. With a median follow-up of 4.8 years, 19
      patients (66%) developed disease recurrence. The patterns of recurrence were
      dependent on histologic subtype. CONCLUSION: Although infrequent, when PD is done
      for primary RPS, resection of additional organs is often required and major
      complication rates are moderate. The recurrence rate is overall high and the
      pattern of recurrence is dictated by histologic subtype.

PMID- 29452863
TI  - Chest wall toxicity after hypofractionated proton beam therapy for liver
      malignancies.
AB  - PURPOSE: Normal liver-sparing with proton beam therapy (PBT) allows for dose
      escalation in the treatment of liver malignancies, but it may result in high
      doses to the chest wall (CW). CW toxicity (CWT) data after PBT for liver
      malignancies are limited, with most published reports describing toxicity after a
      combination of hypofractionated proton and photon radiation therapy. We examined
      the incidence and associated factors for CWT after hypofractionated PBT for liver
      malignancies. METHODS AND MATERIALS: We retrospectively reviewed the charts of 37
      consecutive patients with liver malignancies (30 hepatocellular carcinoma, 6
      intrahepatic cholangiocarcinoma, and 1 metastasis) treated with hypofractionated
      PBT. CWT was scored using Common Terminology Criteria for Adverse Events, version
      4. Receiver-operating characteristic curves were used to identify patient and
      dosimetric factors associated with CWT and to determine optimal dose-volume
      histogram parameters/cutoffs. Cox regression univariate analysis was used to
      associate factors to time-dependent onset of CWT. RESULTS: Thirty-nine liver
      lesions were treated with a median dose of 60 GyE (range, 35-67.5) in 15
      fractions (range, 13-20). Median follow-up was 11 months (range, 2-44). Grade >=2
      and 3 CW pain occurred in 7 (19%) and 4 (11%) patients, respectively. Median time
      to onset of pain was 6 months (range, 1-14). No patients had radiographic rib
      fracture. On univariate analysis, CW equivalent 2 Gy dose with an alpha/beta = 3
      Gy (EQD2alpha/beta=3), V57 >20 cm3 (hazard ratio [HR], 2.7; P = .004), V63 >17
      cm3 (HR, 2.7; P = .003), and V78 >8 cm3 (HR, 2.6; P = .003) had the strongest
      association with grade >=2 CW pain, as did tumor dose of >75 Gy EQD2alpha/beta=10
      (HR, 8.7; P = .03). No other patient factors were associated with CWT.
      CONCLUSIONS: CWT after hypofractionated PBT for liver malignancies is clinically
      relevant. For a 15-fraction regimen, V47 >20 cm3, V50 >17 cm3, and V58 >8 cm3
      were associated with higher rates of CWT. Further investigation of PBT techniques
      to reduce CW dose are warranted.

PMID- 29452862
TI  - Protective Effect of Human Leukocyte Antigen (HLA) Allele DRB1*13:02 on Age
      Related Brain Gray Matter Volume Reduction in Healthy Women.
AB  - BACKGROUND: Reduction of brain volume (brain atrophy) during healthy brain aging
      is well documented and dependent on genetic, lifestyle and environmental factors.
      Here we investigated the possible dependence of brain gray matter volume
      reduction in the absence of the Human Leukocyte Antigen (HLA) allele DRB1*13:02
      which prevents brain atrophy in Gulf War Illness (James et al., 2017). METHODS:
      Seventy-one cognitively healthy women (32-69years old) underwent a structural
      Magnetic Resonance Imaging (sMRI) scan to measure the volumes of total gray
      matter, cerebrocortical gray matter, and subcortical gray matter. Participants
      were assigned to two groups, depending on whether they lacked the DRB1*13:02
      allele (No DRB1*13:02 group, N=60) or carried the DRB1*13:02 allele (N=11). We
      assessed the change of brain gray matter volume with age in each group by
      performing a linear regression where the brain volume (adjusted for total
      intracranial volume) was the dependent variable and age was the independent
      variable. FINDINGS: In the No DRB1*13:02 group, the volumes of total gray matter,
      cerebrocortical gray matter, and subcortical gray matter were reduced highly
      significantly. In contrast, none of these volumes showed a statistically
      significant reduction with age in the DRB1*13:02 group. INTERPRETATION: These
      findings document the protective effect of DRB1*13:02 on age-dependent reduction
      of brain gray matter in healthy individuals. Since the role of this allele is to
      connect to matching epitopes of external antigens for the subsequent production
      of antibodies and elimination of the offending antigen, we hypothesize that its
      protective effect may be due to the successful elimination of such antigens to
      which we are exposed during the lifespan, antigens that otherwise would persist
      causing gradual brain atrophy. In addition, we consider a possible beneficial
      role of DRB1*13:02 attributed to its binding to cathepsin S, a known harmful
      substance in brain aging (Wendt et al., 2008). Of course, other factors covarying
      with the presence of DRB1*13:02 could be involved.

PMID- 29452865
TI  - Stereotactic radiosurgery for multiple brain metastases: Results of multicenter
      benchmark planning studies.
AB  - PURPOSE: Stereotactic radiosurgery is indicated for treatment of multiple brain
      metastases. Various treatment platforms are available, but most comparisons are
      limited to single-center studies. As part of a national commissioning program,
      benchmark planning cases were completed by 21 clinical centers, providing a
      unique dataset of current practice across a large number of providers and
      equipment platforms. METHODS AND MATERIALS: Two brain metastases cases were
      provided, with images and structures predrawn, involving 3 and 7 lesions. Centers
      produced plans according to their local practice, which were reviewed centrally
      using metrics for target coverage, selectivity, gradient fall-off, and normal
      tissue sparing. RESULTS: Fifty plans were submitted, using 24 treatment
      platforms. Eleven plans were revised following feedback, including 2 centers that
      acquired a new platform; 1 other center accepted a restriction of service. All
      centers prioritized coverage, with the prescription isodose covering >=95% of 233
      of 235 target volumes. Selectivity was much more variable, especially for smaller
      lesions, and when combined with poor gradient indices resulted in large volumes
      of normal tissue being irradiated. Tomotherapy submissions were outliers for
      either selectivity or gradient index, but other platforms could produce plans
      with relatively low gradient indices for larger lesion volumes. There was more
      variation among Varian and Elekta LINAC plans than for Gamma Knife and
      CyberKnife, and larger differences for smaller targets, both inter- and
      intratreatment platform. Doses to normal brain and brainstem were highest when
      margins were applied, but improvements were possible by replanning alone.
      CONCLUSIONS: Multicenter benchmarking exercises have highlighted some variation
      in clinical practice and priorities, with a few outliers. Most platforms are able
      to achieve comparable plans, except for the smallest volumes and when larger
      planning margins are used. The data will be used to advance standardization and
      quality improvement of national services and can provide useful guidance for
      centers worldwide.

PMID- 29452864
TI  - Managing motion in conventionally fractionated lung cancer radiation therapy:
      Collaborative quality improvement from a statewide consortium of academic and
      community practices.

PMID- 29452866
TI  - Intrapatient study comparing 3D printed bolus versus standard vinyl gel sheet
      bolus for postmastectomy chest wall radiation therapy.
AB  - PURPOSE: This patient study evaluated the use of 3-dimensional (3D) printed bolus
      for chest wall radiation therapy compared with standard sheet bolus with regard
      to accuracy of fit, surface dose measured in vivo, and efficiency of patient
      setup. By alternating bolus type over the course of therapy, each patient served
      as her own control. METHODS AND MATERIALS: For 16 patients undergoing chest wall
      radiation therapy, a custom 5.0 mm thick bolus was designed based on the
      treatment planning computed tomography scan and 3D printed using polylactic acid.
      Cone beam computed tomography scanning was used to image and quantify the
      accuracy of fit of the 2 bolus types with regard to air gaps between the bolus
      and skin. As a quality assurance measure for the 3D printed bolus, optically
      stimulated luminescent dosimetry provided in vivo comparison of surface dose at 7
      points on the chest wall. Durations of patient setup and image guidance were
      recorded and compared. RESULTS: In 13 of 16 patients, the bolus was printed
      without user intervention, and the median print time was 12.6 hours. The accuracy
      of fit of the bolus to the chest wall was improved significantly relative to
      standard sheet bolus, with the frequency of air gaps 5 mm or greater reduced from
      30% to 13% (P < .001) and maximum air gap dimension diminished from 0.5 +/- 0.3
      to 0.3 +/- 0.3 mm on average. Surface dose was within 3% for both standard sheet
      and 3D printed bolus. On average, the use of 3D printed bolus reduced the setup
      time from 104 to 76 seconds. CONCLUSIONS: This study demonstrates 3D printed
      bolus in postmastectomy radiation therapy improves fit of the bolus and reduces
      patient setup time marginally compared with standard vinyl gel sheet bolus. The
      time savings on patient setup must be weighed against the considerable time
      needed for the 3D printing process.

PMID- 29452867
TI  - Deep inspiration breath hold level variability and deformation in locoregional
      breast irradiation.
AB  - PURPOSE: The purpose of this study was to evaluate the dosimetric effect of
      breath hold level variability and deformation on breast, chest wall, internal
      mammary chain (IMC) nodes, and heart. METHODS AND MATERIALS: Left-sided post
      lumpectomy (n = 12) and postmastectomy (n = 3) patients underwent deep
      inspiration breath hold (DIBH) and exhale breath hold (EBH) computed tomography
      (CT) scans. Forward-planned locoregional breast plans were created on the DIBH
      scan. Two effects were modeled assuming no setup uncertainties: residual motion
      within the gating window and systematically shallow breath hold levels (BHLs).
      Real-time position management (RPM) was used to monitor BHL at simulation and
      during treatment. The RPM data were scaled to simulate BHL variation within
      symmetric gating window widths of +/-1, 3, 5, and 7 mm; the dosimetric impact of
      this motion was simulated in the treatment planning system. Systematically
      "shallow" BHL errors were modeled using deformable image registration to map the
      patient trajectory from DIBH to EBH (n = 12). The deformable vector fields were
      scaled to produce synthetic CT scans modeling patient position during breath
      holds 1, 3, 5, and 7 mm shallower than simulator BHL. The original treatment
      plans were applied to the synthetic CTs and dose was recalculated. RESULTS:
      Acceptable plan quality was maintained for most patients with motion within
      gating windows up to +/-7 mm. Patients with shallow median BHLs experienced loss
      of coverage at simulated gating windows +/-5 mm or larger. At systematic 3 mm
      shallow BHL error, 4/12 patients had clinical target volume IMC V80% < 99%; this
      increased to 11/12 patients at 5 mm. Change in heart dose from systematic BHL
      errors was negligible. CONCLUSIONS: Motion within gating windows has minimal
      dosimetric impact for most BHL variability; however, loss of IMC coverage can
      occur even for small gating windows when BHLs are systematically shallow. This
      can be mitigated by restricting lower BHL tolerances or accounting for known
      uncertainties in planning.

PMID- 29452868
TI  - Chest wall dose reduction using noncoplanar volumetric modulated arc radiation
      therapy for lung stereotactic ablative radiation therapy.
AB  - PURPOSE: Stereotactic ablative radiation therapy (SABR) to lung tumors close to
      the chest wall can cause rib fractures or chest wall pain. We evaluated and
      propose a clinically practical solution of using noncoplanar volumetric modulated
      arc radiation therapy (VMAT) to reduce chest wall dose from lung SABR. METHODS
      AND MATERIALS: Twenty lung SABR VMAT plans in which the chest wall volume
      receiving 30 Gy or higher (V30) exceeded 30 mL were replanned by noncoplanar VMAT
      with opposite 15 degrees  couch kicks. Dosimetric parameters including chest wall
      V30 and V40; lung V5, V10, V20, and mean dose; Paddick high-dose conformity
      index; intermediate-dose conformity index; and monitor units (MU) for each plan
      were used to evaluate the plan quality. The treatment time was also estimated by
      delivering the entire treatment. Two-sided paired t test was used to evaluate the
      difference of the dosimetric parameters between coplanar 1 arc (cVMAT1), coplanar
      2 arcs (cVMAT2), and noncoplanar two arcs (nVMAT2) plans; differences with P <
      .05 were considered statistically significant. RESULTS: V30 and V40 for chest
      wall were reduced on average by 20% +/- 9% and 15% +/- 11% (mean +/- standard
      deviation) from cVMAT2 plans to nVMAT2 plans (P < .01 for both comparisons) and
      by 8% +/- 7% and 16% +/- 13% from cVMAT1 plans to cVMAT2 plans (P < .003 for both
      comparisons). The differences in lung mean dose were <0.2 Gy among cVMAT1,
      cVMAT2, and nVMAT2. There were no significant differences in lung V5, V10, and
      V20. On average, the number of MU increased 14% for nVMAT2 compared with cVMAT2.
      The Paddick high-dose conformity indexes were 0.88 +/- 0.03, 0.89 +/- 0.04, and
      0.91 +/- 0.03, and intermediate-dose conformity indexes were 3.88 +/- 0.49, 3.80
      +/- 0.44 and 3.51 +/- 0.38 for cVMAT1, cVMAT2, and nVMAT2, respectively.
      CONCLUSIONS: We found that noncoplanar VMAT plans are feasible, clinically
      practical to deliver, and significantly reduce V30 and V40 of chest wall without
      increasing lung dose.

PMID- 29452869
TI  - Three-dimensional printer-aided casting of soft, custom silicone boluses (SCSBs)
      for head and neck radiation therapy.
AB  - PURPOSE: Custom tissue compensators provide dosimetric advantages for treating
      superficial or complex anatomy, but currently available fabrication technology is
      expensive or impractical for most clinical operations and yields compensators
      that are difficult for patients to tolerate. We aimed to develop an inexpensive,
      clinically feasible workflow for generating patient-specific, soft, custom
      silicone boluses (SCSBs) for head-and-neck (HN) radiation therapy. METHODS AND
      MATERIALS: We developed a method using 3-dimensional printed parts for generating
      SCSBs for the treatment of HN cancers. The clinical workflow for generation of
      SCSBs was characterized inclusive of patient simulation to treatment in terms of
      resource time and cost. Dosimetric properties such as percentage depth dose and
      dose profiles were measured for SCSBs using GaF films. Comprehensive measurements
      were also conducted on an HN phantom. SCSBs were generated and used for electron
      or photon based radiation treatments of 7 HN patients with lesions at nose,
      cheek, eye, or ears. In vivo dose measurements with optically simulated
      luminescence dosimeters were performed. RESULTS: Total design and fabrication
      time from patient simulation to radiation treatment start required approximately
      1 week, with fabrication constituting 1 to 2 working days depending on bolus
      surface area, volume, and complexity. Computed tomography and dosimetric
      properties of the soft bolus were similar to water. In vivo dose measurements on
      7 treated patients confirmed that the dose deposition conformed to planned doses.
      Material costs were lower than currently available hard plastic boluses generated
      with 3-dimensional printing technology. All treated patients tolerated SCSBs for
      the duration of therapy. CONCLUSIONS: Generation and use of SCSBs for clinical
      use is feasible and effective for the treatment of HN cancers.

PMID- 29452870
TI  - Acute pancreatitis: An unexpected toxicity when combining nivolumab and
      stereotactic body radiation therapy.

PMID- 29452871
TI  - Radiation oncology: What's in a name?

PMID- 29452872
TI  - UroLift as a surrogate for fiducial markers in IGRT planning of prostate cancer
      in BPH patients.

PMID- 29452873
TI  - Toward consensus reporting of radiation-induced liver toxicity in the treatment
      of primary liver malignancies: defining clinically relevant endpoints: In Regard
      to Chapman et al.

PMID- 29452874
TI  - Quality of prostate cancer screening information on the websites of nationally
      recognized cancer centers and health organizations.
AB  - PURPOSE: The purpose of this study was to survey the accessibility and quality of
      prostate-specific antigen (PSA) screening information from National Cancer
      Institute (NCI) cancer center and public health organization Web sites. METHODS
      AND MATERIALS: We surveyed the December 1, 2016, version of all 63 NCI-designated
      cancer center public Web sites and 5 major online clearinghouses from allied
      public/private organizations (cancer.gov, cancer.org, PCF.org, USPSTF.org, and
      CDC.gov). Web sites were analyzed according to a 50-item list of validated health
      care information quality measures. Web sites were graded by 2 blinded reviewers.
      Interrater agreement was confirmed by Cohen kappa coefficient. RESULTS: Ninety
      percent of Web sites addressed PSA screening. Cancer center sites covered 45% of
      topics surveyed, whereas organization Web sites addressed 70%. All organizational
      Web pages addressed the possibility of false-positive screening results; 41% of
      cancer center Web pages did not. Forty percent of cancer center Web pages also
      did not discuss next steps if a PSA test was positive. Only 6% of cancer center
      Web pages were rated by our reviewers as "superior" (eg, addressing >75% of the
      surveyed topics) versus 20% of organizational Web pages. Interrater agreement
      between our reviewers was high (kappa coefficient = 0.602). CONCLUSION: NCI
      designated cancer center Web sites publish lower quality public information about
      PSA screening than sites run by major allied organizations. Nonetheless,
      information and communication deficiencies were observed across all surveyed
      sites. In an age of increasing patient consumerism, prospective prostate cancer
      patients would benefit from improved online PSA screening information from
      provider and advocacy organizations. Validated cancer patient Web educational
      standards remain an important, understudied priority.

PMID- 29452875
TI  - Use of expanders for bowel protection in pediatric pelvic tumor radiation
      therapy: 15 years of tolerance results.
AB  - PURPOSE: Bowel is often the dose-limiting organ in curative pelvic irradiation
      because of radiation enteritis when dose exceeds 40 to 45 Gy. To limit radiation
      enteritis, a silicone tissue-expander prothesis (STEP) connected to a
      subcutaneous self-sealing valve was prospectively used in children undergoing
      pelvic or abdominal radiation therapy. This study reports the 15-year long-term
      outcomes of this prospective series. METHODS AND MATERIALS: Between 1987 and
      2008, 29 children from 3 Paris institutions received pelvic radiation therapy
      after surgical placement of a STEP in the pelvis. The median prescribed dose was
      50.4 Gy (44.1-55 Gy) using 5 daily fractions of 1.8 Gy per week, except for 1
      patient receiving 4 fractions of 2.5 Gy per week. The median treatment duration
      was 40 days (29-49 days). After 2000, computed tomography (CT) conformal 3
      dimensional radiation therapy was used, and 12 patients had CT simulation. Four
      had CT before and after insertion of the STEP, enabling us to compare pre- and
      postprosthesis insertion bowel dose-volume histograms. Acute and late toxicities
      were captured using the Radiation Therapy Oncology Group or the National Cancer
      Institute Common Terminology Criteria for Adverse Events 4.0 scale. RESULTS: No
      patient experienced significant perioperative complications. Pre- and post-STEP
      insertion small bowel dose-volume histograms show significant reductions in small
      bowel: 51%, 45%, and 64%, respectively, in V10, V15, and V40 (Vx = irradiated
      volume by x Gy). Twenty-five patients (86%) completed their radiation therapy
      with no or minimal small bowel toxicity. One patient also treated with neutrons
      developed delayed grade 4 toxicities. The 15-year complication-free survival for
      those surviving was 70.3%. CONCLUSIONS: We report the long-term follow-up of STEP
      prosthesis insertion in children to reduce the small bowel volume in the
      radiation field. The acute and long-term tolerances were excellent. The STEP
      reduced the bowel dose over 40 Gy by 64%.

PMID- 29452876
TI  - Stereotactic body radiation therapy for high-riskprostate cancer: Not ready.

PMID- 29452877
TI  - The split hypoglossal nerve versus the cross-face nerve graft to supply the free
      functional muscle transfer for facial reanimation: A comparative study.
AB  - Long-standing cases of facial paralysis are currently treated with free
      functional muscle transfer. Several nerves are mentioned in the literature to
      supply the free muscle transfer. The aim of this study is to compare the split
      hypoglossal nerve and the cross-face nerve graft to supply the free functional
      muscle transfer in facial reanimation. Of 94 patients with long-standing,
      unilateral facial palsy, 49 were treated using the latissimus dorsi muscle
      supplied by the split hypoglossal nerve, and 45 patients were treated using the
      latissmus dorsi muscle supplied by healthy contralateral buccal branch of the
      facial nerve. The excursion gained by the free muscle transfer supplied by the
      split hypoglossal nerve (mean 19.20 +/- 6.321) was significantly higher (P value
      0.001) than that obtained by the contralateral buccal branch of the facial nerve
      (mean 14.59 +/- 6.245). The split hypoglossal nerve appears to be a good possible
      option to supply the free vascularised muscle transfer in facial reanimation. It
      yields a stronger excursion in less time than the contralateral cross-face nerve
      graft.

PMID- 29452878
TI  - Combining Novel Renal Injury Markers with Delta Serum Creatinine Early after
      Cardiac Surgery and Risk-Stratification for Serious Adverse Outcomes: An
      Exploratory Analysis.
AB  - OBJECTIVE: To evaluate the prognostic utility of multiple novel urinary
      biomarkers of renal injury when used alone, in pair-wise combination with an
      early delta serum creatinine (DeltaSCr) term, and combined as a broad biomarker
      panel for the prediction of serious adverse outcomes that may reflect AKI in
      patients undergoing cardiac surgery. DESIGN: Post-hoc analysis of prospective
      observational study. SETTING: Academic medical center. PARTICIPANTS: 603 adults
      undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Urinary cystatin-c, kidney injury molecule-1, chemokine (C-C motif) ligand 2 and
      interleukin-18 were measured at baseline and <1 hour, 3 hours and 18-24 hours
      after separation from cardiopulmonary bypass (CPB). DeltaSCr-initial was defined
      as the difference in SCr from baseline to first postoperative measure. The
      primary outcome of hospital mortality or renal replacement therapy occurred in 25
      patients. Concordant elevation of any urinary biomarker measured 3 hours after
      CPB together with DeltaSCr-initial >=0 mg.dL-1 provided excellent early risk
      stratification for the primary outcome (OR >=15.1, 95% CI 4.1-55.4). Combining
      four urinary biomarkers together with DeltaSCr-initial and neutrophil gelatinase
      associated lipocalin, previously reported from the same cohort, to provide a 6
      point AKI risk score enabled early identification of patients reaching the
      primary outcome (ROCAUC 0.86, 95% CI 0.79-0.92) with potentially useful
      sensitivity and specificity at varied cut-points. CONCLUSIONS: Combining novel
      urinary biomarkers of renal injury with a creatinine-based metric soon after
      cardiac surgery provided excellent prognostic utility for serious adverse
      outcomes. Future studies are required to confirm these findings and determine
      optimal biomarker combinations for cost-effective risk stratification.

PMID- 29452879
TI  - Augmented Reality and Ultrasound Education: Initial Experience.

PMID- 29452880
TI  - Lucerne cast - LuCa: Functional conservative treatment of extra-articular
      fractures of the proximal phalanges of the fingers (with video).
AB  - Most extra-articular fractures of the proximal phalanges (P1) of the
      triphalangeal fingers can be treated conservatively with good results.
      Prerequisites for successful fracture treatment are intact soft tissue without
      any lesions of the extensor hood and stable initial fracture reduction. The key
      to functional conservative treatment of P1 fractures is to immobilize the
      metacarpophalangeal joints in flexion, resulting in equilibrium of flexor and
      extensor forces across the fracture site, which converts these inherently
      unstable fractures into relatively stable fractures. Precise initial application
      of the cast and regular follow-up of the patient is essential for successful
      treatment. By means of an instructional video, an overview of the equipment
      required is given, and the correct application of a Lucerne Cast is illustrated
      step-by-step.

PMID- 29452881
TI  - Tenosynovial chondromatosis of the wrist presenting with acute carpal tunnel
      syndrome: A case report.
AB  - We report a case of synovial chondromatosis of the wrist that manifested as acute
      carpal tunnel syndrome. The patient successfully underwent carpal tunnel release,
      tenosynovectomy and resection of dorsal and volar ossified bodies embedded in the
      tenosynovium overlying the wrist. Final histopathology confirmed the diagnosis of
      synovial chondromatosis. The patient's symptoms of pain, numbness, and
      paresthesia in a median nerve distribution resolved completely and the patient
      resumed full-time work in the service industry 4-weeks postoperatively with no
      functional limitations. This case highlights the importance of maintaining a
      broad differential in the approach to wrist pain and the role of magnetic
      resonance imaging in the diagnosis of synovial chondromatosis given its variable
      degree of ossification.

PMID- 29452882
TI  - Synthesis, characterisation and DNA intercalation studies of regioisomers of
      ruthenium (II) polypyridyl complexes.
AB  - Regioisomers of the functional group of the main ligand (L) on a series of
      [Ru(phen)2L]2+and [Ru(bpy)2L]2+ complexes, where phen is 1,10 phenanthroline and
      bpy is 2,2'-bipyridine, were synthesised to investigate the interaction with
      deoxyribonucleic acid (DNA) as potential therapeutics. UV-Vis binding titrations,
      thermal denaturation and circular dichroism were used to evaluate their
      interaction with DNA. The conclusions indicated the significance of the auxiliary
      ligand; especially 1,10-phenanthroline has on the binding constants (Kb). The
      systematic variation of auxiliary ligand(phen or bpy), and polypyridyl ligand (4
      (1H-Imidazo[4,5-f][1,10]phenanthrolin-2-yl)benzonitrile (CPIP), 2-(4
      formylphenyl)imidazo[4,5-f] [1,10] phenanthroline (FPIP), 2-(4
      bromophenyl)imidazo[4,5-f][1,10]phenanthroline (BPIP) and 2-(4
      nitrophenyl)imidazo[4,5-f] [1,10] phenanthroline (NPIP), split in terms of
      functional group change were investigated for DNA interaction. The CPIP analogues
      in particular were investigated for the regioisomerism (ortho, meta, para) effect
      of the nitrile group on the ligand. It was found that both the DNA interaction
      could be tailored through the systematic variation of the electronic nature of
      the individual auxiliary ligand and to a lesser extent the functional group and
      regioisomeric change. Preliminary cell line studies have been carried out to
      determine the selectivity of the complexes against cell lines such as A375 (Skin
      Cancer), HeLa (Cervical Cancer), A549 (Lung Cancer), Beas2B (Lung Normal Cell)
      and MCF-7 (Breast Cancer). Complexes which had strong DNA interactions in the
      binding studies have proven to be the most efficacious against certain cell
      lines. Establishing well-defined structure property relationships when looking at
      trends in spectroscopic properties and DNA binding will aid in the intelligent
      design of potential therapeutic complexes.

PMID- 29452883
TI  - Thiocarbonyl-bound metallonitrosyl complexes with visible-light induced DNA
      cleavage and promising vasodilation activity.
AB  - Nitric oxide has been involved in many key biological processes such as
      vasodilation, platelet aggregation, apoptosis, memory function, and this has
      drawn attention to the development of exogenous NO donors. Metallonitrosyl
      complexes are an important class of these compounds. Here, two new ruthenium
      nitrosyl complexes containing a thiocarbonyl ligand, with the formula cis
      [Ru(phen)2(L)(NO)](PF6)3 (phen = phenantroline, L = thiourea or thiobenzamide),
      were synthesized and characterized by electronic spectroscopy, FTIR, NMR, mass
      spectrometry and voltammetric techniques. Theoretical calculations using Density
      Functional Theory (DFT) and Time-dependent Density Functional Theory (TD-DFT)
      were also used and further supported the characterizations of these complexes. An
      efficient release of nitric oxide by blue light was validated using a NO/HNO
      probe: 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, known
      as cPTIO. Interestingly, the complex containing thiourea cleaved DNA even in the
      dark, while both complexes showed great DNA photocleavage activity in blue light.
      This process might work mainly through NO and hydroxyl radical production.
      Additionally, these complexes showed promising vasodilator activity, whose
      mechanism of action was investigated using N-Nitro-l-arginine methyl ester
      hydrochloride (L-NAME) and 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and
      compared to sodium nitroprusside. Both compounds were indeed NO-mediated heme
      dependent activators of soluble guanylate cyclase. Additionally, they did not
      show any significant cytotoxicity against cancer cell lines U87 and GBM02.
      Altogether, these results supported both complexes having potential
      pharmacological applications that deserve further studies.

PMID- 29452884
TI  - Water soluble glucose derivative of thiocarbohydrazone acts as ionophore with
      cytotoxic effects on tumor cells.
AB  - A novel water-soluble ionophore based on the thiocarbohydrazone moiety conjugated
      with glucose (GluTch) was synthesized through a simple two-step procedure.
      Structural elucidation was carried out in water solution by means of various
      spectroscopic techniques (NMR, UV-Vis, and CD), electrospray ionization mass
      spectrometry and density functional theory calculations. The flexible nature of
      the thiocarbohydrazone moiety of the new glycoderivative compound induced both
      different coordination motifs and stoichiometry towards copper and zinc.
      Cytotoxicity assays of the ligands on the human normal keratinocyte NCTC-2544,
      MDA-MB-231 breast cancer and PC-3 human prostate adenocarcinoma cell lines
      demonstrated that i) higher activity on cancer cells growth inhibition compared
      to a normal cell line; ii) the introduction of the glucose unit does not alter
      the cytotoxic activity of the underivatized ionophore ligand and iii) the
      presence of copper ion improves the activity of the thiocarbohydrazones.

PMID- 29452885
TI  - Somatolactogens and diabetic retinopathy.
AB  - IMPORTANCE: Diabetic retinopathy (DR) is one of the most common of all diabetic
      complications. The number of people with DR in the United States is expected to
      increase to 16 million by 2050. DR is the leading cause of blindness among
      working-age adults in many different countries, including the United States. In
      later DR stages, neovascularization is associated with extensive retinal
      capillary non-perfusion and vitreo-proliferation leading to retinal detachment.
      This neovascularization is orchestrated by an imbalance of growth factors in the
      retina from which somatolactogens (pituitary growth hormone, GH-N; placental
      growth hormone, GH-V; prolactin, PRL; and placental lactogen, PL, also referred
      as chorionic somatomammotropin, CSH), may play an important role. OBSERVATIONS:
      Somatolactogens are a group of hormones that share many structural and functional
      features. They are important for physiological changes in pregnancy, for adequate
      development of the fetus, and in the case of GH-N, for promoting growth after
      birth. GH-N is synthesized by the anterior pituitary, GH-V and PL are secreted by
      the placenta, whereas, PRL is synthesized by the anterior pituitary and uterine
      decidua. However, in recent years the expression of GH-N and PRL and their
      receptors have been detected in other tissues including the retina, acting as
      neuroprotective and pro-angiogenic agents. The relationship of GH-N and diabetic
      retinopathy (DR) was established many years ago when it was observed that its
      deficiency was related to regression of DR while an increase in serum levels of
      GH-N, GH-V, and PL promoted DR. While more studies are needed to define the
      potential implications of GH-V and PL in DR pathogenesis, it has been
      demonstrated that GH-N and PRL participate in DR by enhancing neovascularization.
      Some PRL isoforms, however, have shown an anti-angiogenic activity rather than
      pro-angiogenesis and appears to be PRL's main role in the regulation of retinal
      vasculature. CONCLUSIONS: Somatolactogens are a group of hormones with a
      significant role in neuroprotection and angiogenesis regulation in the eye.
      Understanding the mechanisms of angiogenesis regulation by somatolactogens will
      potentially lead to the development of new drugs for DR.

PMID- 29452886
TI  - Shifting the IGF-axis: An age-related decline in human tear IGF-1 correlates with
      clinical signs of dry eye.
AB  - OBJECTIVE: The human corneal epithelium expresses both the insulin-like growth
      factor type 1 receptor (IGF-1R) and the IGF-1R/insulin receptor (INSR) hybrid.
      Despite the previous identification of IGF-1 in human tear fluid, little is known
      regarding the regulation of IGF-1 in tear fluid and its role in corneal
      epithelial homeostasis. In the present study, we investigated the impact of
      biological parameters on the concentration of human tear levels of IGF-1. DESIGN:
      Tear levels of IGF-1 were measured in 41 healthy, human volunteers without any
      reported symptoms of dry eye. All volunteers underwent standard biomicroscopic
      examination of the cornea and tear film. In a subgroup of volunteers, corneal
      staining with sodium fluorescein, tear film break up time and tear production
      using a Schirmer's test strip were measured to assess clinical signs of dry eye.
      Tears were collected from the inferior tear meniscus using glass microcapillary
      tubes and IGF-1 levels were measured using a solid phase sandwich ELISA. RESULTS:
      Tear levels of IGF-1 were highest in young adults and significantly decreased in
      older adults (P = 0.003). There were no differences in tear IGF-1 between males
      and females (P = 0.628). Tear IGF-1 levels were correlated with tear film break
      up time (R = 0.738) and tear production (R = 0.826). CONCLUSIONS: These data
      indicate that there is a progressive decline in tear IGF-1 due to aging that is
      associated with clinical signs of dry eye. This effect is likely due to age
      related changes in the lacrimal gland.

PMID- 29452887
TI  - Protein Intake and Long-term Change in Glomerular Filtration Rate in the Jackson
      Heart Study.
AB  - OBJECTIVE: Dietary protein intake could have deleterious renal effects in
      populations at risk for chronic kidney disease. Here, we examined whether higher
      protein intake (>=80th percentile of energy from protein) is associated with
      decline in kidney function and whether this decline varies by diabetes status.
      DESIGN: Observational cohort study. SUBJECTS AND SETTINGS: Participants were
      African-Americans (n = 5,301), who enrolled in the Jackson Heart Study between
      2000 and 2004. METHODS: Dietary intake was assessed using a validated food
      frequency questionnaire at baseline, and serum creatinine was measured at
      baseline (visit 1) and 8 years later (visit 3). Estimated glomerular filtration
      rates (eGFRs) at baseline and follow-up were computed using the chronic kidney
      disease epidemiology collaboration equation. MAIN OUTCOME MEASURE: The change in
      eGFR was computed by subtracting eGFR at visit 1 from that at visit 3. RESULTS:
      Of 3,165 participants with complete data, 64% were women, 57% had hypertension,
      and 19% had diabetes. The median (25th, 75th percentile) percent energy intake
      from protein was 14.3 (12.4, 16.4), comparable to that reported for the general
      US population (15% of energy). During a median (25th, 75th percentile) follow-up
      of 8.0 (7.4, 8.3) years, eGFR declined by 10.5% from a mean (SD) of 97.4 (17.5)
      to 86.9 (21.3) mL/min/1.73 m2. In the fully adjusted model, consumption of
      protein as percent of energy intake in lowest and highest quintiles was
      associated with decline in eGFR among diabetic subjects. The analysis of variance
      with a robust variance estimator was used to determine whether long-term change
      in eGFR significantly varies by protein intake. CONCLUSIONS: Our results show
      that, among African-Americans with diabetes, higher protein intake as a percent
      of total energy intake is positively associated with greater decline in eGFR in
      analyses that accounted for risk factors for kidney disease.

PMID- 29452888
TI  - Could Low-Protein Diet Modulate Nrf2 Pathway in Chronic Kidney Disease?
AB  - Oxidative stress and inflammation are common findings in chronic kidney disease
      (CKD) patients, and they are directly linked to clinical outcomes such as protein
      energy wasting and cardiovascular disease. Nuclear factor-erythroid 2-related
      factor 2 (Nrf2) is the master regulator of antioxidant genes, regulating the
      expression of detoxifying enzymes of phase II and antioxidant responses.
      Furthermore, Nrf2 can also regulate anti-inflammatory cellular responses, by
      inhibiting nuclear factor kappa B activity (transcription factor that promotes
      inflammation). Therefore, modulating Nrf2 can be a new therapeutic approach to
      reduce inflammation and oxidative stress in CKD. Low-protein diet (LPD)
      prescribed for nondialysis CKD patients presents numerous benefits already well
      established, including reduction of inflammation and oxidative stress. However,
      there is no available data regarding the relationship between LPD and Nrf2
      modulation in these patients. This review aims to discuss the impact, if any, of
      LPD on Nrf2 expression, in nondialysis CKD patients.

PMID- 29452889
TI  - Anthropometric and Biochemical Determinants of Estimated Glomerular Filtration
      Rate in a Large Cohort of Obese Children.
AB  - OBJECTIVE: We aimed to investigate which clinical and metabolic factors could
      influence the estimated glomerular filtration rate (eGFR) levels, evaluating a
      large population of obese children without suspect of primary kidney disease.
      DESIGN: Retrospective, cross-sectional study. SETTING: Pediatric university
      department. SUBJECTS: We enrolled 2,957 obese children and adolescents
      consecutively attending our department between January 2000 and 2017. Inclusion
      criteria were body mass index (BMI) > 95th percentile and eGFR > 90 mL/min/1.73
      m2. Exclusion criteria were secondary forms of obesity, eGFR < 90 mL/min/1.73 m2,
      proteinuria/hematuria at urine dipstick, or consumption of any medication.
      INTERVENTIONS: Weight, waist circumference, height, waist to height ratio (W/Hr),
      BMI-standard deviation score (SDS), pubertal stage, systolic blood pressure (SBP)
      and diastolic blood pressure (DBP), duration of obesity, insulin, eGFR, and
      homeostasis model assessment (HOMA-IR) were obtained. A general linear model was
      performed for a multiple variable analysis. MAIN OUTCOME MEASURE: The population
      was divided in tertiles for BMI-SDS, W/Hr, SBP- and DBP-SDS, HOMA-IR, and
      duration of obesity. We compared eGFR levels among these tertiles. RESULTS: The
      eGFR levels significantly increased across both BMI-SDS and W/Hr tertiles.
      Conversely the eGFR levels significantly decreased across SBP-SDS, HOMA-IR, and
      duration of obesity tertiles. No significant differences in eGFR levels across
      DBP-SDS tertiles were detected. Pubertal patients presented significantly lower
      eGFR values compared with prepubertal patients. A general linear model for eGFR
      variance including as covariates W/Hr, HOMA-IR, duration of obesity, pubertal
      stage, BMI-SDS, and SBP-SDS (model R2 39.7%; model P < .00001) was performed. It
      confirmed a direct association of eGFR values with BMI-SDS and an indirect
      association with HOMA-IR, duration of obesity, pubertal stage, and SBP-SDS.
      CONCLUSIONS: We showed a positive correlation of eGFR with both BMI-SDS and a
      negative one with SBP-SDS, HOMA-IR, pubertal stage, and duration of obesity. The
      duration of obesity was the variable most significantly associated to eGFR
      levels.

PMID- 29452890
TI  - Editorial.

PMID- 29452891
TI  - Effect of topical application of 2% lidocaine gel on corneal sensitivity of
      clinically normal equine eyes.
AB  - OBJECTIVE: To assess the degree and duration of corneal anaesthesia provided by
      topical application of a non-ophthalmic 2% lidocaine gel in horses. STUDY DESIGN:
      Experimental, 'blinded', randomized prospective study. ANIMALS: Twelve adult
      horses without relevant ocular abnormalities. METHODS: Baseline corneal touch
      threshold (CTT) measurements were obtained bilaterally by use of a Cochet-Bonnet
      aesthesiometer just prior to topical treatment. A volume of 0.2mL of 2% lidocaine
      gel was administered in one randomly selected eye and the same volume of a
      viscous lubricant in the other eye to serve as control. The CTT value was
      measured on both eyes 5, 10, 20, 30, 45, 60, 75 and 90 minutes after drug
      application. The potential for local adverse effects following lidocaine gel
      application was also evaluated. RESULTS: Mean CTT baseline measurements were not
      significantly different (p>0.05) between the control eyes (3.41+/-0.56cm) and
      those subsequently treated with the lidocaine gel (3.50+/-0.64cm). In control
      eyes, no significant changes in corneal sensitivity (p>0.05) occurred over time
      during the study period. By contrast, a marked reduction in corneal sensitivity
      was observed after lidocaine application, with mean CTT values significantly
      lower (p<0.001) than those of the control eyes from 5 to 75 minutes. A steady
      state maximal corneal anaesthesia was present from 10 to 45 minutes after
      lidocaine gel application with mean CTT values ranging from 0.21 to 0.45cm.
      Corneal epithelial irregularities were detected in three lidocaine-treated eyes,
      but spontaneous resolution occurred within 24hours. CONCLUSIONS AND CLINICAL
      RELEVANCE: Deep and sustained corneal anaesthesia is achieved after application
      of 2% lidocaine gel to the equine eye, with minimal changes in the corneal
      epithelium. It might be useful for minor ophthalmic surgeries performed in the
      standing sedated horse.

PMID- 29452892
TI  - Association of breastfeeding duration with dyslipidemia in women aged over 20
      years: Korea National Health and Nutrition Examination Survey 2010-2014.
AB  - BACKGROUND: The prevalence of dyslipidemia, particularly hypercholesterolemia,
      has been reported to increase after pregnancy and menopause in Korea. This
      suggests the importance of the management of dyslipidemia in women for preventing
      cardiovascular diseases. OBJECTIVE: This study aimed to examine the association
      of breastfeeding with 5 subtypes of dyslipidemia in Korean women aged over 20
      years, by using the nationally representative Korea National Health and Nutrition
      Examination Survey 2010-2014. METHODS: Ordinary least square regression and
      ordered logistic regression analyses were used to determine the association
      between breastfeeding duration and dyslipidemia. RESULTS: The likelihood of
      having low-density lipoprotein cholesterol (LDL-C) disorder decreased by 16% in
      the group that breastfed for more than 24 months (odds ratio, 0.84; 95%
      confidence interval, 0.75-0.95) compared with the group that did not breastfeed.
      The likelihood of having non-high-density lipoprotein cholesterol (non-HDL-C)
      disorder was significantly reduced by 25% when the breastfeeding duration was
      more than 24 months (odds ratio, 0.75; 95% confidence interval, 0.64-0.87). The
      tendency toward developing disorders of total cholesterol (TC), LDL-C, and non
      HDL-C decreased as the duration of breastfeeding increased, particularly among
      women aged 30-39 years. CONCLUSION: Breastfeeding duration was negatively
      correlated with dyslipidemia in terms of TC, LDL-C, non-HDL-C, and triglycerides.
      Long-term breastfeeding was associated with the prevalence of dyslipidemia-TC,
      LDL-C, non-HDL-C, and TG disorders, in particular.

PMID- 29452893
TI  - A novel mutation in GPIHBP1 causes familial chylomicronemia syndrome.
AB  - Familial chylomicronemia syndrome is characterized by severe elevation in serum
      triglycerides and an increased risk of acute pancreatitis. Although familial
      chylomicronemia syndrome is mainly caused by mutations in the lipoprotein lipase
      (LPL) gene, few causal mutations in other genes (ie, APOC2, APOA5, LMF1, and
      GPIHBP1) have also been reported. In this case report, we present the discovery
      of a novel mutation in the glycosylphosphatidylinositol-anchored high-density
      lipoprotein-binding protein 1 (GPIHBP1) gene and discuss its pathogenicity
      through a familial segregation study.

PMID- 29452894
TI  - Bioprocessing automation in cell therapy manufacturing: Outcomes of special
      interest group automation workshop.
AB  - Phacilitate held a Special Interest Group workshop event in Edinburgh, UK, in May
      2017. The event brought together leading stakeholders in the cell therapy
      bioprocessing field to identify present and future challenges and propose
      potential solutions to automation in cell therapy bioprocessing. Here, we review
      and summarize discussions from the event. Deep biological understanding of a
      product, its mechanism of action and indication pathogenesis underpin many
      factors relating to bioprocessing and automation. To fully exploit the
      opportunities of bioprocess automation, therapeutics developers must closely
      consider whether an automation strategy is applicable, how to design an
      'automatable' bioprocess and how to implement process modifications with minimal
      disruption. Major decisions around bioprocess automation strategy should involve
      all relevant stakeholders; communication between technical and business strategy
      decision-makers is of particular importance. Developers should leverage
      automation to implement in-process testing, in turn applicable to process
      optimization, quality assurance (QA)/ quality control (QC), batch failure
      control, adaptive manufacturing and regulatory demands, but a lack of precedent
      and technical opportunities can complicate such efforts. Sparse standardization
      across product characterization, hardware components and software platforms is
      perceived to complicate efforts to implement automation. The use of advanced
      algorithmic approaches such as machine learning may have application to
      bioprocess and supply chain optimization. Automation can substantially de-risk
      the wider supply chain, including tracking and traceability, cryopreservation and
      thawing and logistics. The regulatory implications of automation are currently
      unclear because few hardware options exist and novel solutions require case-by
      case validation, but automation can present attractive regulatory incentives.

PMID- 29452895
TI  - The ultrasonography evaluation of talar dysplasia as a potential prognostic
      factor for predicting the course and outcomes of clubfoot deformity treatment
      using Ponseti technique.
AB  - OBJECTIVE: The aim of this study was to assess the role of sonographic evaluation
      of Talar dysplasia in predicting the outcome of standard Ponseti method in the
      treatment of clubfoot deformity. METHODS: A total 23 children (15 boys and 8
      girls; mean age: 18.2 +/- 5.4 days (8-32)) who underwent Ponseti treatment were
      included in the study. Before the treatment, maximal talus length of affected and
      non-affected feet were measured by US and relative talar dysplasia ratio (RTDR)
      was calculated. The patients were categorized 2 groups according to RTDR: group A
      - mild and group B - severe deformity. Pirani score was used for clinical
      evaluation. The groups were compared in terms of number of the applied casts,
      need of percutaneous tenotomy of Achilles tendon (AchT) and frequency of
      deformity recurrence. RESULTS: Pirani score was 4.46 for population (4.33 for
      group A; 4.54 for group B). Number of casts significantly differed between groups
      (p < 0.001) and positive correlation was found (r = 0.851, p < 0.001). AchT was
      performed in 56% cases for group A and in 86% cases for group B; no statistically
      significant difference was obtained (p = 0.162). Recurrence occurred in 2
      patients belonging to group B without significant difference compared to group A
      (p = 0.502). CONCLUSION: Talar dysplasia assessment appeared as a promising
      prognostic factor for predicting the outcome of the Ponseti technique in
      treatment of clubfoot deformity. LEVEL OF EVIDENCE: Level IV, diagnostic study.

PMID- 29452897
TI  - ""Hand gestures" in chest pain of coronary origin".

PMID- 29452896
TI  - Do subscapularis tears really result in superior humeral migration?
AB  - OBJECTIVES: The aim of this study was to analyse the effect of subscapularis tear
      on superior humeral excursion (SHE) and acromiohumeral distance (AHD). The
      hypothesis was that subscapularis tears do not result in superior humeral
      excursion. METHODS: Patients who underwent shoulder arthroscopy between August of
      2011 and 2015 were reevaluated. Those with isolated Bankart lesion were used as
      control group and included in the Group 1, isolated full-thickness supraspinatus
      tear in the Group 2, isolated subscapularis tear in the Group 3, and combined
      subscapularis and supraspinatus tear in the Group 4. The mean SHE and AHD
      measurements on magnetic resonance imaging of these groups were compared to
      reveal any difference in superior humeral migration (SHM). RESULTS: There were 30
      patients in each group. The mean age of Group 1 (26.44 +/- 8.34) was younger than
      the other 3 groups. The mean AHD and SHE were higher in Group 1 and 3 (Mean AHD:
      12.89 +/- 2.24 and 12.28 +/- 1.9, respectively. Mean SHE: -3.2 +/- 0.99 and -2.78
      +/- 0.64, respectively) than Group 2 and 4 (Mean AHD: 6.2 +/- 1.78 and 6.16 +/-
      1.52, respectively. Mean SHE: 0.72 +/- 0.65 and 1.24 +/- 0.63, respectively). The
      AHD and SHE were strongly correlated with each other (Pearson correlation
      coefficient = 0.184). The inter-observer and intra-observer correlation of the
      measurements of SHE on MRI were excellent with intraclass correlation coefficient
      of 0.95 and 0.94, respectively. CONCLUSION: Subscapularis tears do not lead to
      SHM and subacromial impingement. However, superior rotator cuff tears can still
      lead to SHM and subacromial impingement even when subscapularis tendon is intact.
      LEVEL OF EVIDENCE: Level III, diagnostic study.

PMID- 29452898
TI  - Transcriptional and epigenetic regulation of innate-like T lymphocyte
      development.
AB  - Invariant Natural Killer T (iNKT) cells are a heterogeneous innate T cell
      population that recognizes lipid antigens. Despite the monospecific nature of
      their T cell receptor, iNKT cells differentiate into stable sublineages during
      thymic development, before foreign antigen encounter. How iNKT cell subsets
      acquire and maintain their functional programs is a central question in innate
      lymphocyte biology. Global transcriptional and epigenetic profiling of iNKT
      subsets has provided insights into the internal wiring of these subsets that
      defines their identity. Comparison of the iNKT transcriptional programs with
      those of other adaptive and innate lymphocyte lineages revealed common core
      regulatory circuits that may dictate effector functions. In this review, we
      summarize recent advances on the molecular mechanisms involved in iNKT cell
      development.

PMID- 29452899
TI  - Influence of dominant- as compared with nondominant-side symptoms on Disabilities
      of the Arm, Shoulder and Hand and Western Ontario Rotator Cuff scores in patients
      with rotator cuff tendinopathy.
AB  - HYPOTHESIS AND BACKGROUND: The Disabilities of the Arm, Shoulder and Hand (DASH)
      questionnaire and the Western Ontario Rotator Cuff (WORC) index are 2 widely used
      patient-reported questionnaires in individuals with rotator cuff (RC)
      tendinopathy. In contrast to the WORC index, for which the items are specific to
      the affected shoulder, the items of the DASH questionnaire assess the ability to
      perform activities regardless of the arm used. The objective of this study is to
      determine whether scores on the DASH questionnaire and WORC index are affected if
      the symptoms are on the dominant or nondominant side in individuals with RC
      tendinopathy. Given the number of items that can be influenced by dominance, the
      hypothesis is that DASH scores will be impacted by the side of the symptoms.
      METHODS: Individuals with RC tendinopathy (N = 149) completed questions on
      symptomatology and hand dominance, the DASH questionnaire, and the WORC index.
      Differences in total scores (independent t test) and single items (Wilcoxon rank
      sum test) were compared between groups of participants with dominant-side
      symptoms and those without dominant-side symptoms. RESULTS: No significant
      differences were observed for WORC or DASH total scores when comparing
      participants with and without symptoms on their dominant side. Single-item
      comparison revealed more items being affected by symptom side on the DASH
      questionnaire (6 of 30 items) than on the WORC index (2 of 21 items).
      CONCLUSIONS: The side of the symptoms does not influence the DASH and WORC total
      scores, as there are no systematic differences between individuals with and
      without symptoms in their dominant shoulder. However, the presence of dominant
      symptoms does influence item scores more on the DASH questionnaire than on the
      WORC index.

PMID- 29452900
TI  - Prevalence and correlates of hypertension-outcome of a free medical screening in
      Oke-Ogun area of Oyo state, Nigeria, West Africa.
AB  - Literature abounds on prevalence of hypertension in Nigeria and urban areas of
      Oyo state but none in Oke-Ogun geopolitical zone, which constitutes 10 local
      governments of the 33 in Oyo state, despite the fact that they have high genetic
      and environmental predisposition to developing high blood pressure. The purpose
      of the study was to determine the prevalence of high blood pressure and
      associated risk factors among indigenes of Oke-ogun, Oyo state. A total of 10,000
      respondents were recruited using proportionate sampling techniques. Hypertension
      was defined according to Joint National Committee-8 criteria. The fasting plasma
      glucose of the respondents were classified as normal (<=6 mmol/L), prediabetes
      (6.1-6.9 mmol/L), and diabetes (>=7 mmol/L). Body mass index was calculated as
      weight (kg)/height (m2) and classified as malnutrition/underweight (<16-18.49),
      normal (18.5-24.9), overweight (25-29.9), and obese (30->=40). Data were analyzed
      using descriptive statistics, Chi-square and binary logistic regression tests at
      P < .05. The mean systolic and diastolic blood pressure was 138 +/- 27.81 and
      86.13 +/- 14.39 respectively. The overall prevalence of hypertension was 38.5%.
      64.1% were diabetics. 63.4% had no formal education. Majority (82.95%) earned
      less than N18,000 ($59) per month. 43.3% had family history of hypertension.
      There is high prevalence of hypertension among the people of Oke-ogun, in Oyo
      state. Their low socioeconomic status, low educational background, malnutrition,
      and genetic predisposition were identified risk factors.

PMID- 29452903
TI  - Extracellular vesicles as key mediators of plant-microbe interactions.
AB  - Extracellular vesicles (EVs) are lipid compartments capable of trafficking
      proteins, lipids, RNA and metabolites between cells. Plant cells have been shown
      to secrete EVs during immune responses, but virtually nothing is known about
      their formation, contents or ultimate function. Recently developed methods for
      isolating plant EVs have revealed that these EVs are enriched in stress response
      proteins and signaling lipids, and appear to display antifungal activity.
      Comparison to work on animal EVs, and the observation that host-derived small
      interfering RNAs and microRNAs can silence fungal genes, suggests that plant EVs
      may also mediate trans-kingdom RNA interference. Many fundamental questions
      remain, however, regarding how plant EVs are produced, how they move, and if and
      how they are taken up by target cells.

PMID- 29452902
TI  - Retina dose as a predictor for visual acuity loss in 106Ru eye plaque
      brachytherapy of uveal melanomas.
AB  - BACKGROUND AND PURPOSE: To evaluate the retina dose as a risk factor associated
      with loss of visual acuity (VA) in 106Ru plaque brachytherapy. MATERIAL/METHODS:
      45 patients receiving 106Ru plaques brachytherapy (median follow-up 29.5 months)
      were included in this study. An in-house developed treatment planning system with
      Monte Carlo based dose calculation was used to perform treatment planning and
      dose calculation. Risk factors associated with loss of VA were evaluated using
      the Cox proportional hazards models, Kaplan-Meier estimates and Pearson
      correlation coefficients. RESULTS: A significant correlation was found between VA
      loss and mean (r = 0.49, p = 0.001) and near maximum (r = 0.47, p = 0.001) retina
      dose D2% and tumor basal diameter (r = 0.50, p < 0.001). The Kaplan-Meier and Cox
      proportional hazards model yielded a significantly higher risk for VA loss
      (>0.3Snellen) for patients receiving a maximum dose of >500 Gy (p = 0.002). A Cox
      multivariate analysis including the macula dose (p = 0.237) and basal diameter (p
      = 0.791) showed that a high maximum retinal dose is the best risk factor (p =
      0.013) for VA loss. CONCLUSION: The study showed that retina dose (D2% and Dmean)
      is a suitable predictor for VA loss.

PMID- 29452901
TI  - Improved cost-effectiveness of short-course radiotherapy in elderly and/or frail
      patients with glioblastoma.
AB  - BACKGROUND AND PURPOSE: Short-course radiotherapy (25 Gy in five fractions) was
      recently shown in a randomized phase III trial to be non-inferior to 40 Gy in 15
      fractions in elderly and/or frail patients with glioblastoma multiforme. This
      study compared the cost-effectiveness of the two regimens. MATERIAL AND METHODS:
      The direct unit costs of imaging, radiotherapy (RT), and dexamethasone were
      collected from the five primary contributing countries to the trial, constituting
      the data of 88% of all patients. Effectiveness was measured by the restricted
      mean overall survival (RMOS) and progression free survival (RMPFS). The
      incremental cost-effectiveness ratio (ICER) was calculated. Indirect costs were
      also estimated for comparison. RESULTS: The median OSs for the short-course and
      commonly used RTs were 8.2 (95% confidence interval [CI] 6.1-10.3) and 7.7 (95%
      CI 5.5-9.9) months, respectively (log rank p = 0.340). Median PFSs were also not
      different (p = 0.686). The differences in the RMOS and the ICER, however, were
      +0.11 life-years and -$3062 United States dollars (USD) per life-year gained,
      respectively. The differences in the RMPFS and the ICER were +0.02 PFS and 
      $17,693 USD, respectively. CONCLUSION: The ICER of -$3062 per life-year gained
      and -$17,693 per PFS gained indicates that the short-course RT is less costly
      compared to the longer RT regimen.

PMID- 29452904
TI  - Leaf nodule symbiosis: function and transmission of obligate bacterial
      endophytes.
AB  - Various plant species establish intimate symbioses with bacteria within their
      aerial organs. The bacteria are contained within nodules or glands often present
      in distinctive patterns on the leaves, and have been used as taxonomic marker
      since the early 20th century. These structures are present in very diverse taxa,
      including dicots (Rubiaceae and Primulaceae) and monocots (Dioscorea). The
      symbionts colonize the plants throughout their life cycles and contribute
      bioactive secondary metabolites to the association. In this review, we present
      recent progress in the understanding of these plant-bacteria symbioses, including
      the modes of transmission, distribution and roles of the symbionts.

PMID- 29452905
TI  - Voiding school as a treatment for daytime incontinence or enuresis: Assessing the
      effectiveness of intervention by measuring changes in wetting episodes.
AB  - BACKGROUND: Most urotherapy interventions are planned for children with daytime
      incontinence or symptoms, and are based on individual education. This study
      conducted a voiding school (VS) program with groups of 4-6 children with daytime
      incontinence or enuresis with or without daytime symptoms. OBJECTIVE: The aim of
      this quasi-experimental study with a one-group pretest-posttest design was to
      assess the effectiveness of the VS intervention for treating children's daytime
      incontinence or enuresis. MATERIALS AND METHODS: Sixty-nine 6-12-year-old
      children with incontinence classified as treatment resistant participated in the
      VS at an outpatient clinic. Based on a power analysis, a sample of 52
      participants was required. The VS involved two whole-day group visits 2 months
      apart. The educational content of the intervention was based on the International
      Children's Continence Society's standards for urotherapy, and was delivered with
      child-oriented teaching methods, including group discussions with peers. The
      primary outcome measure was the number of dry days and nights. The amount of
      wetting was also estimated, and the frequency of voiding measured. Data were
      collected with 1-week voiding diaries before and after each visit. Changes in
      dependent variables between four measurement points was measured by using
      repeated measures variance analysis. The long-term effectiveness was evaluated
      from patient records concerning 3-month follow-up phone calls or other contacts 8
      18 months after the VS. RESULTS: Fifty-eight children, 34 girls and 24 boys,
      completed the study. Twelve children had daytime incontinence, 18 had enuresis,
      and 28 had both. The number of dry days increased from a mean of 3.5-5.3 (P <
      0.001), and the number of dry nights increased from a mean of 2.4-3.9 (P < 0.001)
      (Summary table). Thirteen (22%) children became completely dry. Three of them had
      daytime incontinence, five enuresis, and five both. Twenty-four out of 40 (60%)
      children with daytime incontinence, and 23 out of 46 (50%) children with enuresis
      showed >=50% decrease in wetting episodes. The amount of wetting reduced, but the
      voiding frequency remained unchanged based on the voiding diaries. Twenty-two
      (45%) of the children were completely dry (six had daytime incontinence, nine
      enuresis, and seven both), and 16 (39%) showed further improvement, but eight
      (16%) children remained unchanged 8-18 months after the VS. CONCLUSIONS: Voiding
      school (VS) was an effective intervention for treating both daytime incontinence
      and nocturnal enuresis in children who had not benefited from standard treatment
      and were classified as treatment resistant.

PMID- 29452906
TI  - Extracranial arterial wall volume is increased and shows relationships with
      vascular MRI measures in idiopathic Parkinson's disease.
AB  - OBJECTIVE: Idiopathic Parkinson's disease (IPD) is the second most common
      neurodegenerative disorder, often complicated by dementia. Cardiovascular risk
      factors and spontaneous cerebral emboli (SCE) are strongly associated with
      Alzheimer's (AD) and vascular dementia (VaD). We measured SCE in the middle
      cerebral artery and arterial wall volume in the extracranial arteries in patients
      with IPD and controls, and explored the relationships with structural and
      physiological MRI brain neurovascular measures. PATIENTS AND METHODS: Arterial
      wall volume over 2cm of the axillary and internal carotid arteries (ICA)
      bilaterally was measured by 3-D tomographic ultrasound in 15 IPD patients and 16
      age/gender matched controls. SCE were counted by Transcranial Doppler (TCD) using
      international consensus criteria. Venous to arterial circulation shunting (v
      aCS), usually through a patent foramen ovale (PFO), was measured using a TCD
      technique with intravenous microbubble contrast. Structural and physiological MRI
      brain neurovascular measures, acquired separately, comprised white matter lesion
      volume (WMLV), cerebral blood flow (CBF) and arterial arrival time (AAT).
      RESULTS: Mean (95% CI) axillary and ICA wall volume was higher in IPD patients at
      523 mm3 (446, 600) and 455 mm3 (374, 536) respectively compared with 412 mm3
      (342, 483) and 408 mm3 (362, 454) in controls being significant for the axillary
      artery (p = 0.04). Cerebral WMLV was related to mean arterial wall volume for
      both axillary (r = 0.555, p = 0.009) and ICA (r = 0.559, p = 0.026) in all
      participants. SCE were detected in four IPD patients and three controls (p =
      1.00). Two IPD patients and three controls were positive for a v-aCS equivalent
      to PFO (p = 0.477). CONCLUSION: Although frequent in AD and VaD, neither SCE nor
      v-aCS were associated with IPD. This is the first study to demonstrate arterial
      wall volume is increased in IPD and relates to WMLV.

PMID- 29452907
TI  - Bing-Neel syndrome presenting as gait problems due to spinal cord involvement.

PMID- 29452908
TI  - Gait and posture analysis in patients with maxillary transverse discrepancy,
      before and after RPE.
AB  - AIM: The purpose of this study was to evaluate the effects of the rapid palatal
      expansion (RPE) on posture and gait analysis in subjects with maxillary
      transverse discrepancies. MATERIAL AND METHODS: Forty-one patients between 6 and
      12 years were divided into 3 groups: 10 control subjects (Cs), 16 patients with
      unilateral posterior crossbite (CbMono), 15 patients with maxillary transverse
      discrepancy and no crossbite (Nocb). Every subject underwent gait analysis and
      posturographic examination in order to evaluate the presence of balance
      alterations before (T0) and after (T4) RPE application. The examinations were
      performed through a six-cameras stereophotogrammetric system (60-120Hz, BTS
      S.p.A.) synchronized with two force plates (FP4060, Bertec Corp.). Romberg test
      was performed on a force plate, and the statokinesiogram and joint kinematics
      were evaluated. One-way Anova was performed among the variables after evidence of
      normal distribution (Levene's test for equality of variances) and Kruskal-Wallis
      test (P<0.05), in order to compare the three groups of subjects. While paired t
      test was performed, or Kruskal-Wallis test, instead when comparing pre- and post
      RPE application within the same group of subjects (P<0.05). Tamane T2 or
      Bonferroni correction was applied where needed. RESULTS: The posturographic
      analysis reveal significant differences across the 3 population: 95% power
      frequency in medio-lateral and antero-posterior direction in T0, median frequency
      in medio-lateral direction in T0, mean power frequency in medio-lateral direction
      in T0. Significant differences were also registered in the three-dimensional
      joints kinematics variables, mainly between Cs and Cbmono in T0 and T4 and
      between Cbmono and Nocb in T4. CONCLUSIONS: A detectable correlation between
      dental occlusion and body posture is shown in this study that confirms another
      benefit of the RPE. This was mainly revealed in the dynamic posture where
      modifications at the mandibular level affect the whole body.

PMID- 29452909
TI  - ?

PMID- 29452910
TI  - Three-dimensional evaluation of airway volume changes in two expansion activation
      protocols.
AB  - The purpose of this study was to evaluate the airway volume changes associated
      with rapid maxillary expansion (RME) protocols using different activation rates.
      A sample of forty RME treated cases was classified into two groups according to
      the rate of RME activation (Group A: 0.8mm per day and Group B: 0.5mm per day).
      Three-dimensional images were obtained for each case before and three months
      after expansion. Dolphin imaging software was used to identify landmarks and
      calculate airway volumes. Intraclass correlation coefficient was used to confirm
      reliability and Wilcoxon signed rank tests were used for comparison between the
      initial and final measurements within each group and between groups. Significant
      increase in the nasal cavity volume for both groups was observed (P<0.0001 and
      P=0.001 for groups A and B respectively). The increase in nasopharynx volume was
      significant in the group with a more rapid activation rate (P=0.0006).
      Significant differences between the two groups in post-treatment changes were
      detected in the nasal cavity volume (P<0.0001), nasopharynx volume (P=0.0035),
      and soft palate area (P=0.0081). A more rapid activation rate results in a higher
      volume increase for the nasal cavity and nasopharynx than a slower activation
      rate.

PMID- 29452911
TI  - ?

PMID- 29452912
TI  - COPD: an overlooked cause of excess mortality in patients with rheumatoid
      arthritis.

PMID- 29452914
TI  - Corrigendum to Patient reported outcome measurements in the diagnosis of
      incisional hernia: PROMIS questionnaire, a pilot study [Journal of Surgical
      Research 203(2) (2016) 378-382].

PMID- 29452913
TI  - Photo-immobilized EGF chemical gradients differentially impact breast cancer cell
      invasion and drug response in defined 3D hydrogels.
AB  - Breast cancer cell invasion is influenced by growth factor concentration
      gradients in the tumor microenvironment. However, studying the influence of
      growth factor gradients on breast cancer cell invasion is challenging due to both
      the complexities of in vivo models and the difficulties in recapitulating the
      tumor microenvironment with defined gradients using in vitro models. A defined
      hyaluronic acid (HA)-based hydrogel crosslinked with matrix metalloproteinase
      (MMP) cleavable peptides and modified with multiphoton labile nitrodibenzofuran
      (NDBF) was synthesized to photochemically immobilize epidermal growth factor
      (EGF) gradients. We demonstrate that EGF gradients can differentially influence
      breast cancer cell invasion and drug response in cell lines with different EGF
      receptor (EGFR) expression levels. Photopatterned EGF gradients increase the
      invasion of moderate EGFR expressing MDA-MB-231 cells, reduce invasion of high
      EGFR expressing MDA-MB-468 cells, and have no effect on invasion of low EGFR
      expressing MCF-7 cells. We evaluate MDA-MB-231 and MDA-MB-468 cell response to
      the clinically tested EGFR inhibitor, cetuximab. Interestingly, the cellular
      response to cetuximab is completely different on the EGF gradient hydrogels:
      cetuximab decreases MDA-MB-231 cell invasion but increases MDA-MB-468 cell
      invasion and cell number, thus demonstrating the importance of including cell
      microenvironment interactions when evaluating drug targets.

PMID- 29452916
TI  - From the editor: A run of success in treating atherosclerotic vascular disease.

PMID- 29452915
TI  - Effect of male body mass index on assisted reproduction treatment outcome: an
      updated systematic review and meta-analysis.
AB  - Men with a body mass index (BMI) of 30 or over are more likely to have reduced
      fertility and fecundity rates. This systematic review and meta-analysis evaluated
      the effect of male BMI on IVF and intracytoplasmic sperm injection (ICSI)
      outcome. An electronic search for published literature was conducted in MEDLINE
      and EMBASE between 1966 and November 2016. Outcome measures were clinical
      pregnancy rates (CPR) and live birth rates (LBR) per IVF or ICSI cycle. Eleven
      studies were identified, including 14,372 cycles; nine reported CPR and seven
      reported LBR. Pooling of data from those studies revealed that raised male BMI
      was associated with a significant reduction in CPR (OR 0.78, 95% CI 0.63 to 0.98,
      P = 0.03) and LBR (OR 0.88, 95% CI 0.82 to 0.95, P = 0.001) per IVF-ICSI
      treatment cycle. Male BMI could be an important factor influencing IVF-ICSI
      outcome. More robust studies are needed to confirm this conclusion using
      standardized methods for measuring male BMI, adhering to the World Health
      Organization definitions of BMI categories, accounting for female BMI, IVF and
      ICSI cycle characteristics, including the number of embryos transferred and
      embryo quality, and use the live birth rate per cycle as primary outcome.

PMID- 29452917
TI  - Roundtable on etiology of familial chylomicronemia syndrome.

PMID- 29452918
TI  - Predictors of safe discharge for pediatric drowning patients in the emergency
      department.
AB  - OBJECTIVES: The purpose of this study is to determine if stable, well-appearing,
      drowning patients who have normal age-adjusted vital signs and pulse oximetry
      upon arrival to the emergency department may be safely discharged without a
      prolonged observation period. METHODS: Medical records were retrospectively
      reviewed for drowning patients presenting to a single pediatric emergency
      department from 1995 to 2014. Data were collected on vital signs and pulse
      oximetry at presentation, chest x-ray results, disposition and complications for
      each encounter. Patients were identified as having either normal or abnormal
      initial vital signs and pulse oximetry, and were compared based on disposition
      and complication rates. RESULTS: Two hundred seventy-six records were initially
      evaluated and 91 were excluded. Thirty-six percent had normal age-adjusted vital
      signs upon arrival. Patients with abnormal temperature, respiratory rate or pulse
      oximetry, as well as those with any abnormal initial cardiopulmonary physical
      exam findings, abnormal mental status, or chest radiograph findings, were more
      likely to be admitted to the hospital. Eight patients developed respiratory
      complications after presentation to the emergency department. Those with abnormal
      pulse oximetry readings on arrival were more likely to develop complications.
      Only two patients who developed complications had initially normal vital signs
      and each had evidence of clinical deterioration within 1h of arrival.
      CONCLUSIONS: The overall complication rate in initially stable, well-appearing
      drowning patients is low. An abnormal pulse oximetry reading at presentation may
      help predict subsequent complications. Those patients with normal age-adjusted
      vital signs and physical exam at presentation may not require a prolonged
      observation period.

PMID- 29452919
TI  - High dose insulin for beta-blocker and calcium channel-blocker poisoning.
AB  - BACKGROUND/OBJECTIVES: High dose insulin (HDI) is a standard therapy for beta
      blocker (BB) and calcium channel-blocker (CCB) poisoning, however human case
      experience is rare. Our poison center routinely recommends HDI for shock from BBs
      or CCBs started at 1U/kg/h and titrated to 10U/kg/h. The study objective was to
      describe clinical characteristics and adverse events associated with HDI.
      METHODS: This was a structured chart review of patients receiving HDI for BB or
      CCB poisoning with HDI defined as insulin infusion of >=0.5U/kg/h. RESULTS: In
      total 199 patients met final inclusion criteria. Median age was 48years (range 14
      89); 50% were male. Eighty-eight patients (44%) were poisoned by BBs, 66 (33%) by
      CCBs, and 45 (23%) by both. Median nadir pulse was 54 beats/min (range 12-121);
      median nadir systolic blood pressure was 70mmHg (range, 30-167). Forty-one
      patients (21%) experienced cardiac arrest; 31 (16%) died. Median insulin bolus
      was 1U/kg (range, 0.5-10). Median starting insulin infusion was 1U/kg/h (range
      0.22-10); median peak infusion was 8U/kg/h (range 0.5-18). Hypokalemia occurred
      in 29% of patients. Hypoglycemia occurred in 31% of patients; 50% (29/50)
      experienced hypoglycemia when dextrose infusion concentration <=10%, and 30%
      (31/105) experienced hypoglycemia when dextrose infusion concentration >=20%.
      CONCLUSIONS: HDI, initiated by emergency physicians in consultation with a poison
      center, was feasible and safe in this large series. Metabolic abnormalities were
      common, highlighting the need for close monitoring. Hypoglycemia was more common
      when less concentrated dextrose maintenance infusions were utilized.

PMID- 29452920
TI  - Patient centered medical homes did not improve access to timely follow-up after
      ED visit.
AB  - BACKGROUND: Patients newly insured through coverage expansion under the
      Affordable Care Act (ACA) may have difficulty obtaining timely primary care
      follow-up appointments after emergency department (ED) discharge. We evaluated
      the association between availability of timely follow-up appointment with
      practice access improvements, including patient-centered medical home (PCMH)
      designations or extended-hours appointments. METHODS: We performed a secret
      shopper audit of primary care practices in greater New Haven, Connecticut. Two
      callers, posing as patients discharged from the ED, called these practices
      requesting follow-up appointments. They followed standardized scripts varying in
      ED diagnosis (uncontrolled hypertension, acute back pain) and insurance status
      (commercial, exchange, Medicaid). We linked our findings with data from a
      previously completed survey that assessed practice characteristics and examined
      the associations between appointment availability and practice access
      improvements. RESULTS: Of the 58 included primary care practices, 49 (84.5%)
      completed both the audit and the survey. Overall, 167/536 calls (31.2%) obtained
      an appointment in 7days. Practices with PCMH designation were less likely to
      offer appointments within 7days (23.4% vs. 33.1%, p=0.03). However, callers were
      more likely to obtain an appointment in 7days from practices offering after-hour
      appointments (36.3% vs. 27.8%, p=0.04). After adjusting for insurance type, there
      were no significant associations between practice improvements and 7-day
      appointment availability or appointment wait time. CONCLUSION: PCMH designation
      and extended-hours appointments were not associated with improved availability of
      timely primary care follow-up appointment for discharged ED patients. EDs should
      engage local clinicians and other stakeholders to strengthen linkage and care
      transition with outpatient practices.

PMID- 29452921
TI  - Comparison of primary compliance in electronic versus paper prescriptions
      prescribed from the emergency department.

PMID- 29452923
TI  - Statistical and machine learning approaches to predicting protein-ligand
      interactions.
AB  - Data driven computational approaches to predicting protein-ligand binding are
      currently achieving unprecedented levels of accuracy on held-out test datasets.
      Up until now, however, this has not led to corresponding breakthroughs in our
      ability to design novel ligands for protein targets of interest. This review
      summarizes the current state of the art in this field, emphasizing the recent
      development of deep neural networks for predicting protein-ligand binding. We
      explain the major technical challenges that have caused difficulty with
      predicting novel ligands, including the problems of sampling noise and the
      challenge of using benchmark datasets that are sufficiently unbiased that they
      allow the model to extrapolate to new regimes.

PMID- 29452922
TI  - Structural biology of the separase-securin complex with crucial roles in
      chromosome segregation.
AB  - The cysteine protease separase opens the cohesin ring by cleaving its kleisin
      subunit and is a pivotal cell cycle factor for the transition from metaphase to
      anaphase. It is inhibited by forming a complex with the chaperone securin, and in
      vertebrates, also by the Cdk1-cyclin B1 complex. Separase is activated upon the
      destruction of securin or cyclin B1 by the proteasome, after ubiquitination by
      the anaphase-promoting complex/cyclosome (APC/C). Here we review recent
      structures of the active protease segment of Chaetomium thermophilum separase in
      complex with a substrate-mimic inhibitor and full-length Saccharomyces cerevisiae
      and Caenorhabditis elegans separase in complex with securin. These structures
      define the mechanism for substrate recognition and catalysis by separase, and
      show that securin has extensive contacts with separase, consistent with its
      chaperone function. They confirm that securin inhibits separase by binding as a
      pseudo substrate.

PMID- 29452924
TI  - Incidental hepatic lesions detected on breast MRI: Rate of malignancy and
      implications for utilization.
AB  - OBJECTIVE: The objective of this study was to determine the rate of malignancy in
      incidentally detected T2 hyperintense hepatic lesions at breast MRI. METHODS:
      Incidental hepatic lesions identified during breast MRI, for which abdominal
      imaging was recommended, were retrospectively analyzed. RESULTS: Of the hepatic
      lesions, 97.3% were benign, and 2.7% were malignant, with a significant
      association between indication for the breast MRI and the malignancy status of
      the hepatic lesion (Fisher's Exact, P < 0.0142). CONCLUSION: Our initial
      experience suggests the benign nature of incidentally detected T2 hyperintense
      hepatic lesions at breast MRI in women without a newly diagnosed breast cancer.

PMID- 29452925
TI  - Utility of sagittal MR imaging of the whole spine in cases of known or suspected
      single-level spinal infection: Overkill or good clinical practice?
AB  - OBJECTIVE: Multi-sequence sagittal magnetic resonance imaging (MRI) of the entire
      spine is performed in patients with known single level spondylodiscitis. Our
      objective is to determine the frequency of multifocal infection. METHODS: After
      IRB approval, a retrospective five-year review of all patients with
      spondylodiscitis was performed. RESULTS: MRI identified 82 patients with single
      level infection. All 82 had entire spine imaging performed within 72 h of
      admission, showing additional non-continuous sites of infection in 19 patients
      (23%). Remote levels of spondylodiscitis were present in 11 patients (13%).
      CONCLUSION: Multi-sequence sagittal MRI of the entire spine may be helpful in
      patients with known single-level spine infection.

PMID- 29452926
TI  - Designing artificial metabolic pathways, construction of target enzymes, and
      analysis of their function.
AB  - Artificial design of metabolic pathways is essential for the production of useful
      compounds using microbes. Based on this design, heterogeneous genes are
      introduced into the host, and then various analysis and evaluation methods are
      conducted to ensure that the target enzyme reactions are functionalized within
      the cell. In this chapter, we list successful examples of useful compounds
      produced by designing artificial metabolic pathways, and describe the methods
      involved in analyzing, evaluating, and optimizing the target enzyme reaction.

PMID- 29452927
TI  - Toward prediction and control of antibiotic-resistance evolution.
AB  - The emergence of antibiotic-resistant bacteria is a serious public concern. To
      deal with this problem, recent advances in technology and the use of laboratory
      evolution experiments have provided valuable information on the phenotypic and
      genotypic changes that occur during the evolution of resistance. These studies
      have demonstrated the existence of evolutionary constraints on the development of
      drug-resistance, which suggests predictability in its evolution. In this review,
      we focus on the possibility to predict and control the evolution of antibiotic
      resistance, based on quantitative analysis of phenotypic and genotypic changes
      observed in bacterial laboratory evolution. We emphasize the key challenges in
      evolutionary biology that will contribute to the development of appropriate
      treatment strategies for preventing resistance evolution.

PMID- 29452928
TI  - Comprehensive on-line two-dimensional liquid chromatography * supercritical fluid
      chromatography with trapping column-assisted modulation for depolymerised lignin
      analysis.
AB  - Lignin depolymerisation produces a large variety of low molecular weight phenolic
      compounds that can be upgraded to value-added chemicals. Detailed analysis of
      these complex depolymerisation mixtures is, however, hampered by the lack of
      resolving power of traditional analysis techniques. In this study, a novel online
      comprehensive two-dimensional reversed-phase liquid chromatography (RPLC) *
      supercritical fluid chromatography (SFC) method with trapping column interface
      was developed for the separation of phenolic compounds in depolymerised lignin
      samples. The trapping capacities of different trapping columns were evaluated.
      The influence of large volume water-containing injection on SFC performance was
      studied. The relation between peak capacity and first dimension flow rate and
      gradient was investigated. The optimized method was applied for the analysis of a
      depolymerised lignin sample. The RPLC * SFC system exhibited high degree of
      orthogonality. Compared with traditional loop based interface, trapping column
      interface can significantly shorten the analysis time and offer higher
      detectability, with the disadvantage of more severe undersampling in the first
      dimension.

PMID- 29452929
TI  - The short-term effectiveness of low-level laser, phonophoresis, and iontophoresis
      in patients with lateral epicondylosis.
AB  - STUDY DESIGN: Randomized parallel group trial. INTRODUCTION: Various treatment
      options for lateral epicondylosis have been reported in the literature. PURPOSE
      OF STUDY: We aimed to compare the effectiveness of low-level laser therapy
      (LLLT), phonophoresis, and iontophoresis in terms of pain, function, and grip
      strength. METHODS: This study that comprised 37 patients with lateral
      epicondylosis was planned as a prospective randomized parallel group trial.
      Twelve participants were randomized to the LLLT group, 12 to the phonophoresis
      group, and 13 to the iontophoresis group. The Visual Analog Scale (VAS), pressure
      algometer, the Patient-Rated Tennis Elbow Evaluation, and grip strength
      dynamometer were used to measure outcomes. The measurements were performed at
      baseline and at the end of 15 sessions. RESULTS: Investigation of the pain scores
      revealed that all VAS scores were improved in both the laser and iontophoresis
      groups (VAS at rest: P = .015, effect size (ES) = 1.49 and P = .016, ES = 0.58,
      respectively; VAS during activity: P = .008, ES = 1.05 and P = .008, ES = 1.16,
      respectively; VAS at night: P = .013, ES = 1.01 and P = .016, ES = 0.72,
      respectively). Only advance in function and grip strength was associated with the
      iontophoresis group (Patient-Rated Tennis Elbow Evaluation P = .006, ES = 0.78;
      grip strength with elbow extension P = .011, ES = 1.03; with elbow flexion P =
      .003, ES = 0.52). DISCUSSION: The most effective approach could not be
      highlighted among the existing studies in the literature as they were applied in
      combination with other therapies. CONCLUSION: In our study, we observed that LLLT
      provides a benefit only for pain, whereas iontophoresis is beneficial for both
      pain and function. If the effect size is evaluated, LLLT is more influential than
      iontophoresis for decreasing pain. However, when we compared phonophoresis and
      iontophoresis in terms of effectiveness, we found that iontophoresis has better
      effects for pain, function, and grip strength.

PMID- 29452930
TI  - Mechanism-specific rehabilitation management of complex regional pain syndrome:
      Proposed recommendations from evidence synthesis.
AB  - STUDY DESIGN: Narrative review. INTRODUCTION: There are a variety of treatments
      with demonstrated effectiveness for the management of complex regional pain
      syndrome (CRPS). However given the variability in symptom presentation in this
      population, therapists may be unsure what treatments would be most effective for
      individual clients. PURPOSE OF THE STUDY: To present a brief synthesis of the
      literature and propose a rehabilitation version of a mechanism-specific
      management algorithm to guide personalized treatment of CRPS. METHODS: A
      systematic search of the literature was conducted to identify all randomized
      controlled trials, systematic reviews, and clinical practice guidelines
      addressing rehabilitation of CRPS. Results were reviewed independently by 2
      reviewers and final selection of articles was reached by consensus, Data was
      extracted using standardized forms, and a single rater gave quality ratings. Both
      reviewers then used the extracted data to present a synthesis of the evidence
      categorized by the proposed mechanisms of effect. RESULTS: A total of 111
      articles were retrieved and reviewed for inclusion; 49 were selected for data
      extraction. A synthesis of the key recommendations was compiled into a
      rehabilitation-specific version of the mechanism-based management algorithm
      proposed by Gierthmuhlen et al (2014). CONCLUSIONS: Consideration of mechanism
      appropriate rehabilitation interventions may assist therapists to select the most
      appropriate and effective treatments from the body of evidence supporting
      rehabilitation of CRPS.

PMID- 29452931
TI  - Identification of novel uncertainty factors and thresholds of toxicological
      concern for health hazard and risk assessment: Application to cleaning product
      ingredients.
AB  - Uncertainty factors (UFs) are commonly used during hazard and risk assessments to
      address uncertainties, including extrapolations among mammals and experimental
      durations. In risk assessment, default values are routinely used for interspecies
      extrapolation and interindividual variability. Whether default UFs are sufficient
      for various chemical uses or specific chemical classes remains understudied,
      particularly for ingredients in cleaning products. Therefore, we examined
      publicly available acute median lethal dose (LD50), and reproductive and
      developmental no-observed-adverse-effect level (NOAEL) and lowest-observed
      adverse-effect level (LOAEL) values for the rat model (oral). We employed
      probabilistic chemical toxicity distributions to identify likelihoods of
      encountering acute, subacute, subchronic and chronic toxicity thresholds for
      specific chemical categories and ingredients in cleaning products. We
      subsequently identified thresholds of toxicological concern (TTC) and then
      various UFs for: 1) acute (LD50s)-to-chronic (reproductive/developmental NOAELs)
      ratios (ACRs), 2) exposure duration extrapolations (e.g., subchronic-to-chronic;
      reproductive/developmental), and 3) LOAEL-to-NOAEL ratios considering
      subacute/acute developmental responses. These ratios (95% CIs) were calculated
      from pairwise threshold levels using Monte Carlo simulations to identify UFs for
      all ingredients in cleaning products. Based on data availability, chemical
      category-specific UFs were also identified for aliphatic acids and salts,
      aliphatic alcohols, inorganic acids and salts, and alkyl sulfates. In a number of
      cases, derived UFs were smaller than default values (e.g., 10) employed by
      regulatory agencies; however, larger UFs were occasionally identified. Such UFs
      could be used by assessors instead of relying on default values. These approaches
      for identifying mammalian TTCs and diverse UFs represent robust alternatives to
      application of default values for ingredients in cleaning products and other
      chemical classes. Findings can also support chemical substitutions during
      alternatives assessment, and data dossier development (e.g., read across),
      identification of TTCs, and screening-level hazard and risk assessment when
      toxicity data is unavailable for specific chemicals.

PMID- 29452933
TI  - Dronedarone-induced liver injury. A case report.

PMID- 29452932
TI  - Occult abusive injuries in children brought for care after intimate partner
      violence: An exploratory study.
AB  - Children in homes with intimate partner violence (IPV) are at increased risk for
      physical abuse. We determined the frequency and injury patterns in children who
      underwent child abuse consultation after IPV exposure by retrospectively
      analyzing the "Examination of Siblings To Recognize Abuse" cohort of children
      referred for physical abuse. Children were selected who presented after IPV
      exposure. Among 2890 children evaluated by child abuse pediatricians, 61 (2.1%)
      patients presented after IPV exposure. Of the 61, 11 (18.0%) were exposed to IPV,
      but had no direct involvement in the IPV event, 36 (59.0%) sustained inadvertent
      trauma during IPV, and 14 (23.0%) were directly assaulted during IPV. Thirty-six
      patients (59.0%) had an injury: 31 (51.0%) had cutaneous injuries and 15 (24.6%)
      had internal injuries including fracture(s), intracranial or intra-abdominal
      injury. Of the 15 patients with internal injuries, 14 (93.3%) were less than 12
      months old. Among the 36 patients with injuries, 16 (44.4%) had no report of
      direct injury, a report of a mechanism that did not explain the identified
      injuries, or a report of trauma without a specific mechanism. Five (13.9%) did
      not have physical examination findings to suggest the extent of their internal
      injuries. Injuries are present in a significant proportion of children presenting
      to Emergency Departments after IPV exposure. History and physical examination
      alone are insufficient to detect internal injuries especially in infants. These
      preliminary results support the need for future, prospective studies of occult
      injury in children exposed to IPV.

PMID- 29452934
TI  - Evaluation of leader peptides that affect the secretory ability of a multiple
      bacteriocin transporter, EnkT.
AB  - EnkT is a novel ATP-binding cassette (ABC) transporter responsible for secretion
      of four bacteriocins, enterocins NKR-5-3A, C, D, and Z (Ent53A, C, D, and Z),
      produced by Enterococcus faecium NKR-5-3. It is generally recognized that the
      secretion of a bacteriocin requires a dedicated ABC transporter, although
      molecular mechanisms of this secretion are yet to be revealed. In order to
      characterize the unique ability of EnkT to secrete multiple bacteriocins, the
      role of N-terminal leader peptides of bacteriocin precursors was evaluated using
      Ent53C precursor as a model. The 18-amino acid leader peptide of Ent53C (Lc) was
      modified by site-directed mutagenesis to generate various point mutations,
      truncations, or extensions, and substitutions with other leader peptides. The
      impact of these Lc mutations on Ent53C secretion was evaluated using a
      quantitative antimicrobial activity assay. We observed that Ent53C production
      increased with Ala substitution of the highly conserved C-terminal double glycine
      residues that are recognized as the cleavage site. In contrast, Ent53C
      antimicrobial activity decreased, with decrease in the length of the putative
      alpha-helix-forming region of Lc. Furthermore, EnkT recognized and transported
      Ent53C of the transformants possessing heterologous leader peptides of enterocin
      A, pediocin PA-1, brochocins A and B, and lactococcins Qalpha and Qbeta. These
      results indicated that EnkT shows significant tolerance towards the sequence and
      length of leader peptides, to secrete multiple bacteriocins. This further
      demonstrates the functional diversity of bacteriocin ABC transporters and the
      importance of leader peptides as their recognition motif.

PMID- 29452936
TI  - Use of telemedicine in the management of infectious diseases.
AB  - Communication technologies have invaded our daily lives. Several studies have
      assessed these technologies in the management of infectious diseases (mainly
      HIV). Weekly short text messages and real-time compliance monitoring assessed in
      HIV patients are both associated with higher compliance in low-income countries.
      Virtual consultations to monitor stable chronic HIV patients or tuberculosis
      treatment in high-income countries appear to be acceptable and efficient.
      Although assessed in small studies, virtual monitoring seems to reinforce the
      doctor-patient relationship and the relation between primary care settings and
      hospitals in various infectious diseases (endocarditis, urinary tract infection,
      skin and soft tissue infection, HIV, tuberculosis, hepatitis C). A better
      prevention of infectious diseases (mainly sexually transmitted infections) seems
      to be observed with telemedicine tools. As fees for teleconsultation or
      telemonitoring have yet to be defined, the development and evaluation (cost
      effectiveness) of these tools are difficult. The regulatory framework will need
      to be improved to encourage such developments, all the while ensuring the
      confidentiality of data. The development of new tools will require the
      collaboration of physicians, users, and healthcare systems.

PMID- 29452937
TI  - Epigenetic chromatin modification by amber suppression technology.
AB  - The genetic incorporation of unnatural amino acids (UAAs) into proteins by amber
      suppression technology provides unique avenues to study protein structure,
      function and interactions both in vitro and in living cells and organisms. This
      approach has been particularly useful for studying mechanisms of epigenetic
      chromatin regulation, since these extensively involve dynamic changes in
      structure, complex formation and posttranslational modifications that are
      difficult to access by traditional approaches. Here, we review recent
      achievements in this field, emphasizing UAAs that help to unravel protein-protein
      interactions in cells by photo-crosslinking or that allow the biosynthesis of
      proteins with defined posttranslational modifications for studying their function
      and turnover in vitro and in cells.

PMID- 29452935
TI  - E3 Ligase VHL Promotes Group 2 Innate Lymphoid Cell Maturation and Function via
      Glycolysis Inhibition and Induction of Interleukin-33 Receptor.
AB  - Group 2 innate lymphoid cells (ILC2s) are a specialized subset of lymphoid
      effector cells that are critically involved in allergic responses; however, the
      mechanisms of their regulation remain unclear. We report that conditional
      deletion of the E3 ubiquitin ligase VHL in innate lymphoid progenitors minimally
      affected early-stage bone marrow ILC2s but caused a selective and intrinsic
      decrease in mature ILC2 numbers in peripheral non-lymphoid tissues, resulting in
      reduced type 2 immune responses. VHL deficiency caused the accumulation of
      hypoxia-inducible factor 1alpha (HIF1alpha) and attenuated interleukin-33 (IL-33)
      receptor ST2 expression, which was rectified by HIF1alpha ablation or inhibition.
      HIF1alpha-driven expression of the glycolytic enzyme pyruvate kinase M2
      downmodulated ST2 expression via epigenetic modification and inhibited IL-33
      induced ILC2 development. Our study indicates that the VHL-HIF-glycolysis axis is
      essential for the late-stage maturation and function of ILC2s via targeting IL-33
      ST2 pathway.

PMID- 29452939
TI  - Surgical site infection-the next frontier in global surgery.

PMID- 29452938
TI  - Harnessing natural DNA modifying activities for editing of the genome and
      epigenome.
AB  - The introduction of site-specific DNA modifications to the genome or epigenome
      presents great opportunities for manipulating biological systems. Such changes
      are now possible through the combination of DNA-modifying enzymes with targeting
      modules, including dCas9, that can localize the enzymes to specific sites. In
      this review, we take a DNA modifying enzyme-centric view of recent advances. We
      highlight the variety of natural DNA-modifying enzymes-including DNA
      methyltransferases, oxygenases, deaminases, and glycosylases-that can be used for
      targeted editing and discuss how insights into the structure and function of
      these enzymes has further expanded editing potential by introducing enzyme
      variants with altered activities or by improving spatiotemporal control of
      modifications.

PMID- 29452940
TI  - Combining bedaquiline and delamanid to treat multidrug-resistant tuberculosis.

PMID- 29452942
TI  - Early safety and efficacy of the combination of bedaquiline and delamanid for the
      treatment of patients with drug-resistant tuberculosis in Armenia, India, and
      South Africa: a retrospective cohort study.
AB  - BACKGROUND: Bedaquiline and delamanid have been approved for treatment of
      multidrug-resistant (MDR) tuberculosis in the past 5 years. Because of
      theoretical safety concerns, patients have been unable to access the two drugs in
      combination. Medecins Sans Frontieres has supported the use of combination
      bedaquiline and delamanid for people with few treatment options since 2016. We
      describe early safety and efficacy of regimens containing the bedaquiline and
      delamanid combination in patients with drug-resistant tuberculosis in Yerevan,
      Armenia; Mumbai, India; and Khayelitsha, South Africa. METHODS: We
      retrospectively analysed a cohort of all patients who received 6-12 months of
      oral bedaquiline and delamanid in combination (400 mg bedaquiline once per day
      for 2 weeks, then 200 mg bedaquiline three times per week and 100 mg delamanid
      twice per day) in MSF-supported projects. We report serious adverse events, QTc
      corrected using the Fridericia formula (QTcF) interval data, and culture
      conversion data during the first 6 months of treatment. FINDINGS: Between Jan 1,
      2016, and Aug 31, 2016, 28 patients (median age 32.5 years [IQR 28.5-40.5], 17
      men) were included in the analysis. 11 (39%) of 28 patients were HIV-positive. 24
      patients (86%) had isolates resistant to fluoroquinolones; 14 patients (50%) had
      extensively drug-resistant tuberculosis. No patient had an increase of more than
      500 ms in their QTcF interval. Four patients (14%) had six instances of QTcF
      increase of more than 60 ms from baseline but none permanently discontinued the
      drugs. 16 serious adverse events were reported in seven patients. Of 23
      individuals with positive baseline cultures, 17 (74%) converted to negative by
      month 6 of treatment. INTERPRETATION: Use of the bedaquiline and delamanid
      combination appears to reveal no additive or synergistic QTcF-prolonging effects.
      Access to bedaquiline and delamanid in combination should be expanded for people
      with few treatment options while awaiting the results of formal clinical trials.
      FUNDING: Medecins Sans Frontieres (MSF).

PMID- 29452943
TI  - Effect of episiotomy training with beef tongue and sponge simulators on the self
      confidence building of midwifery students.
AB  - This study assesses the efficacy of simulation-based episiotomy training (SBET)
      with beef tongue and sponge models in terms of the self confidence of midwifery
      students while performing episiotomy. Third-year midwifery students from
      Cumhuriyet University in the fall semesters of 2011 and 2012 were enrolled in the
      sponge and beef tongue model groups (n = 36 and n = 37, respectively). A
      checklist was prepared on the required skills for performing episiotomy which can
      be broken into three main parts, namely preparation, cutting and repairing and
      completion. According to the checklist, a Likert type questionnaire was developed
      including 5 items for preparation, 11 items for cutting and repairing, and 6
      items for completion. After SBET with the sponge and beef tongue models in our
      laboratories of Midwifery Department, the students performed episiotomy steps in
      laboring women in Sivas State Hospital and then they filled in the questionnaire
      to indicate whether they gained self-confidence in performing episiotomy or not.
      Although, participants of both groups have successfully completed all the steps
      of episiotomy, overall, beef tongue model was found to be more successful
      regarding their self-confidence (p < 0.05), including the skills in performing
      local anesthesia; choosing needle holder, suture material and scissor for
      cutting; identifying apex, hymen and skin; using needle holder properly while
      penetrating into the skin, suturing vaginal mucosa until hymen, knotting, and
      suturing perineal muscles and skin. Our results suggest that while SBET with both
      models are applicable for episiotomy training of midwifery students in the
      laboratory setting, SBET with beef tongue model provides an additional increase
      in their self-confidence in the clinical settings.

PMID- 29452944
TI  - Iron-engineered mesoporous silica nanocatalyst with biodegradable and catalytic
      framework for tumor-specific therapy.
AB  - Inorganic mesoporous silica-based nanovehicles are highly promising for drug
      delivery but still suffer from the disadvantages of lacking functionality and
      poor biodegradability on account of the inert silica framework. Moreover,
      conventional cancer therapeutics typically employ toxic anticancer drugs or
      invasive external irradiations, which will inevitably give rise to severe adverse
      effects and diminished therapeutic outcome. In this work, we report on the iron
      engineered framework of mesoporous silica nanoparticles (MSNs) to fabricate a
      nanocatalyst with biodegradable and catalytic framework via a "dissolution
      regeneration" strategy (designated as rFeOx-HMSN). Based on the abundant
      overexpressed hydrogen peroxide (H2O2) and mild acidic nature in tumor
      microenvironment (TME), rFeOx-HMSN nanocatalyst could trigger in-situ Fenton-like
      reactions to produce highly toxic hydroxyl radicals (.OH), causing remarkable
      oxidative damages against tumor cells/xenografts. Additionally, the iron
      engineered rFeOx-HMSN nanocatalyst could readily collapse via an iron-extraction
      strategy under protein-rich environment, thereby improving the biodegradability
      of rFeOx-HMSN nanocatalyst. This work paves a promising way to engineer the inert
      framework of MSN into functional, biodegradable and catalytic nanoplatform,
      featuring effective tumor-therapeutic outcome and stimuli-responsive
      biodegradation concurrently.

PMID- 29452945
TI  - Reduction-sensitive fluorescence enhanced polymeric prodrug nanoparticles for
      combinational photothermal-chemotherapy.
AB  - In this study, a reduction-sensitive supramolecular polymeric drug delivery
      system was developed for combinational photothermal-chemotherapy of cancer. The
      multifunctional system was self-assembled by specific host-guest interactions
      between hydrophilic beta-cyclodextrin functionalized hyaluronic acid and
      adamantane linked camptothecin/dye conjugate, where a near-infrared (NIR)
      absorbing dye IR825 was loaded. The hydrophilic hyaluronic acid shell endows the
      assembly with excellent colloidal stability and biocompatibility. The embedded
      disulfide bond in the camptothecin/dye conjugate was cleaved under reducing
      environment, leading to the release of the conjugated drug and the recovery of
      fluorescence emission. Meanwhile, the dye IR825 could efficiently transfer the
      absorbed light into local heat, making the nanoplatform an effective system for
      photothermal therapy. As evident by confocal microscopy images, the nanoplatform
      was quickly internalized by HeLa, MCF-7, and U14 cancer cells and released drug
      molecules inside the cells. In vitro cell viability assays confirmed that the
      cancer cells were efficiently killed by the treatment of the nanoplatform under
      NIR light irradiation. Significant tumor regression was also observed in the
      tumor-bearing mice upon the administration of the nanoplatform through
      combinational photothermal-chemotherapy therapy. Hence, this nanoplatform
      presented a great potential in site-specific combined photothermal-chemotherapy
      of tumor.

PMID- 29452946
TI  - Time-responsive osteogenic niche of stem cells: A sequentially triggered, dual
      peptide loaded, alginate hybrid system for promoting cell activity and osteo
      differentiation.
AB  - The efficacy of stem cell-based bone tissue engineering has been hampered by cell
      death and limited fate control. A smart cell culture system with the capability
      of sequentially delivering multiple factors in specific growth stages, like the
      mechanism of the natural extracellular matrix modulating tissue formation, is
      attractive for enhancing cell activity and controlling cell fate. Here, a bone
      forming peptide-1 (BFP-1)-laden mesoporous silica nanoparticles (pep@MSNs)
      incorporated adhesion peptide, containing the arginine-glycine-aspartic acid
      (RGD) domain, modified alginate hydrogel (RA) system (pep@MSNs-RA) was developed
      to promote the activity and stimulate osteo-differentiation of human mesenchymal
      stem cells (hMSCs) in sequence. The survivability and proliferation of hMSCs were
      enhanced in the adhesion peptide modified hydrogel. Next, BFP-1 released from
      pep@MSNs induced hMSCs osteo-differentiation after the proliferation stage.
      Moreover, BFP-1 near the cells was self-captured by the additional cell-peptide
      cross-linked networks formed by the ligands (RGD) binding to receptors on the
      cell surface, leading to long-term sustained osteo-stimulation of hMSCs. The
      results suggest that independent and sequential stimulation in proliferation and
      osteo-differentiation stages could synergistically enhance the survivability,
      expansion, and osteogenesis of hMSCs, as compared to stimulating alone or
      simultaneously. Overall, this study provided a new and valid strategy for stem
      cell expansion and osteo-differentiation in 2D or 3D culture systems, possessing
      potential applications in 3D bio-printing and tissue regeneration.

PMID- 29452947
TI  - Highly stable molybdenum dioxide nanoparticles with strong plasmon resonance are
      promising in photothermal cancer therapy.
AB  - Photothermal therapy (PTT) is one of promising cancer therapy with high
      efficiency and minimal invasiveness. Exploiting of perfect PTT agent is vital to
      improve the therapy. In this study, a new type of bow tie-like molybdenum dioxide
      (MoO2) nanoparticles was successfully synthesized. These nanobow-ties had strong
      localized surface plasmon resonance (SPR) effect from visible to near infrared
      regions, and exhibited ultrahigh chemical stability. They could not only
      withstand high temperature heating without oxidation, but also resist the
      corrosion of strong acid and alkali. Meanwhile, the MoO2 nanoparticles were
      highly stable in protein-containing biological medium, though they partly
      degraded in PBS solution. Both in vivo and in vitro experiments indicated that
      they exhibited inappreciable toxicity. Under illumination of near infrared laser,
      they showed excellent PTT effect, as revealed by significant inhibition of cancer
      cell viability in vitro and efficient destruction in tumor tissue growth in vivo.
      These MoO2 nanoparticles possessed highly chemical stability and low toxicity
      with high PTT efficiency, thus promising them high potential as nanoagent in
      cancer treatment.

PMID- 29452948
TI  - Photo-tearable tape close-wrapped upconversion nanocapsules for near-infrared
      modulated efficient siRNA delivery and therapy.
AB  - RNA interference (RNAi) has become an appealing therapeutic approach for cancer
      and other diseases. One key challenge is the effective protection of these small
      fragile biomolecules against complicated physiological environments as well as
      efficient on-demand release. Here we design a photo-tearable polymer tape close
      wrapped nanocapsule for efficient NIR modulated siRNA delivery. The photo
      tearable nanocapsules comprise core-shell upconversion nanoparticles (UCNPs)
      coated with mesoporous silica layer for loading of photosensitizer hypocrellin A
      (HA) and small interfering RNA (siRNA) against polo-like kinase 1 (PLK1), and
      covalently bound thin membranes of polyethylene glycol (PEG) via a synthesized
      photocleavable linker (PhL). Upon irradiation at 980 nm, the UCNPs produce UV
      emissions to break PhL and tear out PEG membrane for siRNA release, and blue
      emissions to activate HA for generating reactive oxygen species (ROS). The close
      PEG membrane wrapping not only guarantees the efficient intracellular
      photocleavage, but also extends the circulation time and protects the loaded
      cargos from leakage and degradation. The ROS assists endosomal escape of the
      loaded cargos, therefore effectively improves the gene silencing efficiency and
      the suppressions of cell proliferation in vitro and tumor growth in vivo. The
      proposed photo-tearable tape-wrapped nanocapsules have promising potential
      application in precision medicine.

PMID- 29452949
TI  - Estimation of the effectiveness ratio (alpha/beta) for resistant cancer cells in
      U87MG human glioblastoma.
AB  - Glioblastoma contains self-renewing, tumorigenic cancer stem-like cells that
      contribute to tumor initiation and therapeutic resistance. The aim of this
      research was to estimate and compare the effectiveness ratio (alpha/beta) of stem
      like cells and differentiated glioma cells derived from the U87MG glioblastoma
      cell line. Cell survival experiments were obtained in a dose range of 0-20 Gy
      (13.52 +/- 0.09 Gy/h) as a hyperfractionationated accelerated radiotherapy
      scheme. Biochemical characterization of the post-irradiated cells was performed
      by flow cytometry analysis and the percentage of stem-like cells that resisted
      irradiation was determined by the CD133 expression. Results showed that U87MG
      stem-like cells are highly proliferative and more radioresistant than the U87MG
      adherent group (with a lesser stem-like character), this in association with the
      calculated alpha/beta ratio of 17 and 14.1, respectively.

PMID- 29452951
TI  - Antibacterial Weapons: Targeted Destruction in the Microbiota.
AB  - The intestinal microbiota plays an important role in health, particularly in
      promoting intestinal metabolic capacity and in maturing the immune system. The
      intestinal microbiota also mediates colonization resistance against pathogenic
      bacteria, hence protecting the host from infections. In addition, some bacterial
      pathogens deliver toxins that target phylogenetically related or distinct
      bacterial species in order to outcompete and establish within the microbiota. The
      most widely distributed weapons include bacteriocins, as well as contact
      dependent growth inhibition and type VI secretion systems. In this review, we
      discuss important advances about the impact of such antibacterial systems on
      shaping the intestinal microbiota.

PMID- 29452950
TI  - Dynamic Fungal Cell Wall Architecture in Stress Adaptation and Immune Evasion.
AB  - Deadly infections from opportunistic fungi have risen in frequency, largely
      because of the at-risk immunocompromised population created by advances in modern
      medicine and the HIV/AIDS pandemic. This review focuses on dynamics of the fungal
      polysaccharide cell wall, which plays an outsized role in fungal pathogenesis and
      therapy because it acts as both an environmental barrier and as the major
      interface with the host immune system. Human fungal pathogens use architectural
      strategies to mask epitopes from the host and prevent immune surveillance, and
      recent work elucidates how biotic and abiotic stresses present during infection
      can either block or enhance masking. The signaling components implicated in
      regulating fungal immune recognition can teach us how cell wall dynamics are
      controlled, and represent potential targets for interventions designed to boost
      or dampen immunity.

PMID- 29452953
TI  - The Archaellum: An Update on the Unique Archaeal Motility Structure.
AB  - Each of the three domains of life exhibits a unique motility structure: while
      Bacteria use flagella, Eukarya employ cilia, and Archaea swim using archaella.
      Since the new name for the archaeal motility structure was proposed, in 2012, a
      significant amount of new data on the regulation of transcription of archaella
      operons, the structure and function of archaellum subunits, their interactions,
      and cryo-EM data on in situ archaellum complexes in whole cells have been
      obtained. These data support the notion that the archaellum is evolutionary and
      structurally unrelated to the flagellum, but instead is related to archaeal and
      bacterial type IV pili and emphasize that it is a motility structure unique to
      the Archaea.

PMID- 29452952
TI  - Phasevarions of Bacterial Pathogens: Methylomics Sheds New Light on Old Enemies.
AB  - A wide variety of bacterial pathogens express phase-variable DNA
      methyltransferases that control expression of multiple genes via epigenetic
      mechanisms. These randomly switching regulons - phasevarions - regulate genes
      involved in pathogenesis, host adaptation, and antibiotic resistance. Individual
      phase-variable genes can be identified in silico as they contain easily
      recognized features such as simple sequence repeats (SSRs) or inverted repeats
      (IRs) that mediate the random switching of expression. Conversely, phasevarion
      controlled genes do not contain any easily identifiable features. The study of
      DNA methyltransferase specificity using Single-Molecule, Real-Time (SMRT)
      sequencing and methylome analysis has rapidly advanced the analysis of
      phasevarions by allowing methylomics to be combined with whole
      transcriptome/proteome analysis to comprehensively characterize these systems in
      a number of important bacterial pathogens.

PMID- 29452954
TI  - WITHDRAWN: Clinical correlates of cerebral white matter abnormalities in patients
      with Parkinson's disease: Methodological issues.
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- 29452955
TI  - Yips preceding baseball-related dystonia.

PMID- 29452956
TI  - Comparison of face-to-face interaction and the electronic medical record for
      venous thromboembolism risk stratification using the 2005 Caprini score.
AB  - OBJECTIVE: Perioperative venous thromboembolism (VTE) risk can be quantified with
      the 2005 Caprini score. The Caprini score has previously been validated by review
      of the electronic medical record (EMR) in >3000 plastic surgery patients.
      However, the accuracy of Caprini-based risk stratification using the EMR, as
      opposed to face-to-face contact with the patient, remains unknown. METHODS:
      Plastic and reconstructive surgery patients who had surgery under general
      anesthesia, required postoperative admission, and were started on enoxaparin
      prophylaxis were identified. The 2005 Caprini scores were calculated
      retrospectively using EMR review only (no direct contact with the patients) to
      establish cohort 1. The 2005 Caprini scores were calculated prospectively using
      face-to-face interaction with the patients, followed by EMR review, to establish
      cohort 2. For all included patients, EMR review or face-to-face screening was
      personally performed by the authors. We compared the proportions of patients with
      identified Caprini risk factors and the aggregate risk scores of patients between
      cohorts. RESULTS: Complete data were available for 536 unique patients in the EMR
      review cohort and 207 unique patients in the face-to-face cohort. Patients whose
      risk scores were calculated face to face had higher Caprini scores than those
      calculated by EMR review alone. The face-to-face cohort had a higher proportion
      of patients risk stratified as Caprini 7-8 (29.5% vs 24.8%) and Caprini >8 (26.6%
      vs 10.5%) compared with the EMR review cohort. Patients risk stratified by face
      to-face discussion were significantly more likely to be stratified into a higher
      risk Caprini stratum. Face-to-face discussion identified a 2-fold increase in
      patients with personal history of deep venous thrombosis (12.6% vs 6.3%; P =
      .005), a 3-fold increase in patients with family history of VTE (16.9% vs 5.2%; P
      < .001), and a 20-fold increase in patients with personal history of multiple
      lost pregnancies (13.6% vs 0.6%; P < .001) compared with EMR review. Observed
      differences for family history of VTE and history of pregnancy loss persisted
      after propensity score analysis, created using component variables in the 2005
      Caprini score plus gender; this supports the conclusion that observed differences
      were not due to site variation or case mix. CONCLUSIONS: When it is used in
      isolation, the EMR may provide inaccurate estimation of patient-level VTE risk
      using the 2005 Caprini score. This study demonstrates that EMR review may miss
      key VTE risk factors, such as personal or family history of VTE, history of
      pregnancy loss, and others; this omission results in lower estimates of
      perioperative VTE risk. The importance of provider-patient interaction for
      accurate VTE risk stratification cannot be overstated.

PMID- 29452957
TI  - A systematic review of the efficacy and limitations of venous intervention in
      stasis ulceration.
AB  - BACKGROUND: Surgical techniques to address various components of chronic venous
      disease are rapidly evolving. Their efficacy and generally good results in
      treating superficial venous reflux (SVR) have been documented and compared in
      patients presenting with pain and swelling. A growing amount of literature is now
      available suggesting their efficacy in patients with venous leg ulcer (VLU). This
      review attempts to summarize the efficacy and limitations of commonly used venous
      interventions in the treatment of SVR and incompetent perforator veins (IPVs) in
      patients with VLU. METHODS: A systematic review of the published literature was
      performed. Two different searches were conducted in MEDLINE, Embase, and
      EBSCOhost to identify studies that examined the efficacy of SVR ablation and IPV
      ablation on healing rate and recurrence rate of VLU. RESULTS: In the whole
      review, 1940 articles were screened. Of those, 45 were included in the SVR
      ablation review and 4 in the IPV ablation review. Data were too heterogeneous to
      perform an adequate meta-analysis. The quality of evidence assessed by the
      Grading of Recommendations Assessment, Development, and Evaluation for the two
      outcomes varied from very low to moderate. Ulcer healing rate and recurrence rate
      were between 70% and 100% and 0% and 49% in the SVR ablation review and between
      59% and 93% and 4% and 33% in the IPV ablation review, respectively. To explain
      those variable results, limitations such as inadequate diagnostic techniques,
      saphenous size, concomitant calf pump dysfunction, and associated deep venous
      reflux are discussed. CONCLUSIONS: Currently available minimally invasive
      techniques correct most venous pathologic processes in chronic venous disease
      with a good sustainable healing rate. There are still specific diagnostic and
      efficacy limitations that mandate proper match of individual patients with the
      planned approach.

PMID- 29452958
TI  - BRCA1 mutation spectrum, functions, and therapeutic strategies: The story so far.
AB  - BRCA1 gene mutations account for about 25-28% of hereditary Breast Cancer as
      BRCA1 is included in the category of high penetrance genes. Except for few
      commonmutations, there is a heterogenous spectrum of BRCA1 mutations in various
      ethnic groups. 185AGdel and 5382ins Care the most common BRCA1 alterations
      (founder mutations) which have been identified in most of the population. This
      review has been compiled with an aim to consolidate the information on genetic
      variants reported in BRCA1 found in various ethnic groups, their functional
      implications if known; involvement of BRCA1 in various cellular
      pathways/processes and potential BRCA1 targeted therapies. The pathological
      variations of BRCA1 vary among different ethical groups. A systematic search in
      PubMed and Google scholar for the literature on BRCA1 gene was carried out to
      figure out structure and function of BRCA1 gene. BRCA1 is a large protein having
      1863 amino acids with multiple functional domains and interacts with multiple
      proteins to carry out various crucial cellular processes. BRCA1 plays a major
      role in maintaining genome integrity, transcription regulation, chromatin
      remodeling, cell cycle checkpoint control, DNA damage repair, chromosomal
      segregation, and apoptosis. Studies investigating the phenotypic response of
      mutant BRCA1 protein and comparing it to wildtype BRCA1 protein are clinically
      important as they are involved in homologous recombination and other repair
      mechanisms. These studies may help in developing more targetted therapies,
      detecting novel interacting partners, identification of new signaling pathways
      that BRCA1 is a part of or downstream target genes that BRCA1 affects.

PMID- 29452959
TI  - Differential expressions of MDM2 and TAP73 in cancer and cancer-adjacent tissues
      in patients with non-small-cell lung carcinoma.
AB  - AIM: To investigate the differences in mRNA and protein expressions of MDM2
      (mouse double minute 2 homolog) and P73 in cancer and cancer-adjacent tissues in
      patients with non-small-cell lung carcinoma (NSCLC). MATERIALS AND METHODS: We
      compared the protein expressions of MDM2 and P73 in lung cancer and cancer
      adjacent tissues in NSCLC patients by IHC (immunohistochemistry) and WB (Western
      blot). We divided the NSCLC patients into two subgroups, adenocarcinoma and
      squamous carcinoma. The mRNA expressions of two main isoforms of P73, TAP73 and
      DNP73, as well as the ratio of DNP73/TAP73 were analyzed by qPCR (quantitative
      real-time PCR) in the two tissues in all NSCLC patients and in patients with
      adenocarcinoma or squamous carcinoma, respectively. RESULTS: WB results did not
      show significant differences in MDM2 and P73 protein expressions in lung cancer
      and cancer-adjacent tissues. However, IHC results indicated that MDM2 expression
      significantly increased in cancer tissues in female patients, but not male
      patients. In addition, TAP73 mRNA expression significantly increased in cancer
      tissues in all NSCLC patients (p=0.002) and in patients with adenocarcinoma
      (p=0.01); while there was no significant difference in DNP73 mRNA expression.
      Hence the fold-change of DNP73/TAP73 ratio significantly decreased (p=0.0003) in
      cancer tissues in all NSCLC patients and in patients with adenocarcinoma.
      CONCLUSIONS: TAP73 mRNA expression significantly increased in cancer tissues than
      cancer-adjacent tissues in all NSCLC patients and in patients with
      adenocarcinoma. Meanwhile, the fold-change of DNP73/TAP73 ratio was similar to
      TAP73. MDM2 protein expression significantly increased in cancer tissues in
      female NSCLC patients.

PMID- 29452960
TI  - Traditionally practiced medicinal plant extracts inhibit the ergosterol
      biosynthesis of clinically isolated dermatophytic pathogens.
AB  - OBJECTIVE: Dermatophytes are resistant to some available antibiotics. Development
      of new plant drugs to control drug resistant microbes is urgently needed. This
      study evaluates the antidermatophytic potential of 18 selected medicinal plants
      used by traditional healers in Theni and Virudhunagar Districts of Tamil Nadu,
      India. MATERIALS AND METHODS: Selected plant parts were collected, shade dried
      and powdered. Plant powders were extracted with ethanol and their antifungal
      potency was investigated against and clinical dermatophytes. The antioxidant
      effect of the extracts was screened using DPPH assay. Minimal Inhibitory
      Concentration (MIC) and Minimal Fungicidal Concentration (MFC) were estimated for
      the extracts. Ten plant extracts showed maximum MFC and they were selected to
      study their efficacy in interfering with ergosterol biosynthesis. Fluconazole
      35MUg/mL known fungicide was used as control. The most active extracts were taken
      for biocompatibility studies using 3T3-L1 fibroblast cell lines. RESULTS: The
      ethanol extract of Phyllanthus reticulates leaves showed good antifungal activity
      compared to other plant extracts. The MIC and MFC for Phyllanthus reticulatus
      were 62.5 and 250MUg/mL against M. pachydermatitis and T. rubrum respectively.
      The ethanol extracts of Phyllanthus reticulatus, Coldenia procumbens, Thespesia
      populnea and Senna alata significantly lowered the release of ergosterol by
      16.37, 19.53, 24.79, and 21.44%, respectively. The ethanol extract of Phyllanthus
      reticulatus leaves was more biocompatible to host cells than other active
      extracts. CONCLUSION: Our study indicated that the ethanol extract of Phyllanthus
      reticulates leaves showed promising activity against dermatophytes. It could be a
      potential material for future development of antidermatophytic agents.

PMID- 29452962
TI  - The role of resiliency and coping strategies in occurrence of positive changes in
      medical rescue workers.
AB  - BACKGROUND: Working in the emergency services entails exposure to traumatic
      events; however, their effects can be both negative and positive. Among the
      factors determining posttraumatic growth (PTG) after an experienced trauma are
      the personal resources and coping strategies. The purpose of the research was to
      investigate the role of resiliency and coping strategies with stress in
      posttraumatic growth in a group of medical rescue workers. MATERIALS AND METHODS:
      Data of 80 male medical rescuers who have experienced traumatic event in their
      worksite were analyzed. The Posttraumatic Growth Inventory, Resiliency
      Measurement Scale and Inventory to Measure Coping Strategies with Stress - Brief
      Cope were used in the study. Statistical tests such as t test, correlation and
      path analysis were used. RESULTS: The tested medical rescue workers revealed the
      medium level of PTG. Active coping, planning, turning to religion, seeking of
      social support, both emotional and instrumental, and self-distraction positively
      correlated with posttraumatic growth. A more significant role in the process of
      PTG appeared to be played by avoidance and emotional-focused strategies Although
      resiliency does not directly affect posttraumatic growth, it may strengthen it
      through the choice of coping strategies. CONCLUSIONS: In the process of
      posttraumatic growth avoidance strategies seem to play more important role than
      strategies focusing on the problem.

PMID- 29452961
TI  - Dipeptidyl peptidase-4 inhibitors (DPP-4i) combined with vitamin D3: An
      exploration to treat new-onset type 1 diabetes mellitus and latent autoimmune
      diabetes in adults in the future.
AB  - Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by
      destruction of pancreatic beta cells through cell injury caused primarily by
      cytotoxic T lymphocytes (CD8+). The pathophysiological basis of T1DM seems to be
      an imbalance between a reduced function of T regulatory lymphocytes and an
      increased inflammatory activity of Th17 lymphocytes caused by increased
      production of inflammatory cytokines, as IL-1beta, IL-6, IL-17 and IFN-gamma due
      to environmental factors and genetic predisposition. The preservation of the
      reserve of beta cells in new-onset T1DM and latent autoimmune diabetes in adults
      (LADA) by immunomodulation in addition to the incretin effect seems to be
      possible with an association of DPP-4 inhibitors and vitamin D3. In this review,
      we discuss the effects of both drugs on the immune system and on beta cell
      function and their eventual additive effects in preserving the residual function
      of beta cells in new-onset T1DM and LADA.

PMID- 29452963
TI  - Chemical sensing in development and function of intestinal lymphocytes.
AB  - The immune system of the intestinal tract has the challenging task of recognizing
      and eliminating intestinal pathogens while maintaining tolerance to dietary and
      commensal antigens; therefore, it must be able to sense environmental cues within
      the intestine and mount suitable responses dictated by their pathogenic or
      nonpathogenic nature. The aryl hydrocarbon receptor (AHR) was originally
      characterized as a chemical sensor of the environmental pollutant 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) [12]. More recently, AHR has emerged as a
      major chemical sensor expressed in many intestinal immune cells that enables them
      to distinguish nutritional and microbial cues and is, therefore, important for
      development, maintenance and function of the intestinal immune system. In this
      review, we will highlight recent advances in our knowledge of the role of AHR
      signaling in intestinal innate lymphoid cells (ILC), T cells and B cells.

PMID- 29452964
TI  - Risk factors for platelet transfusion in glioblastoma surgery.
AB  - The objectives of this study are to identify risk factors for and to evaluate
      clinical outcomes of platelet transfusion in glioblastoma surgery. The medical
      records of adult patients who underwent craniotomy for glioblastoma resection at
      a single academic medical center were retrospectively reviewed. We stratified
      patients into 2 groups: those who were transfused at least 1 unit of platelets
      intraoperatively or postoperatively (no more than 7 days after surgery), and
      those who were not transfused with platelets. Through the use of a 1:3 matched
      cohort analysis, we compared complications, length of stay, discharge
      disposition, and mortality, across groups. One hundred and five consecutive adult
      patients were included in this study. Thirteen patients (12.38%) received
      platelet transfusions. Prior antiplatelet therapy (odds ratio [OR] 8.21, 95%
      confidence interval [CI]: 2.36-28.58), preoperative platelet count less than
      200,000 cells/uL (OR 8.46, 95% CI: 2.16-33.22), and longer operative times (OR
      1.73, 95% CI: 1.10-2.72) were significant risk factors for platelet transfusion.
      There were no significant differences in the outcomes of interest in the matched
      cohort analysis.

PMID- 29452966
TI  - Gender differences in the relationship of childhood trauma and the course of
      illness in schizophrenia.
AB  - INTRODUCTION: Different types of childhood trauma have been repeatedly shown to
      contribute to psychotic symptoms. Gender differences in schizophrenia are well
      known. Some studies argue that trauma history means a significantly higher risk
      of psychosis for women than men. However, there is evidence of early adverse life
      events to be associated with higher stress-sensitivity in men. Little is known
      about the connection of specific type of trauma and specific psychotic symptoms
      as well as the course of illness with explicit regard to gender differences.
      METHODS: 102 men and women with schizophrenia spectrum disorder were tested using
      Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Scale for Assessing
      Positive Symptoms, Early Trauma Inventory-SR. RESULTS: Although, women had a
      later age at onset without regarding trauma history (d = 0.74), this difference
      became non-significant when introducing trauma variables. Patients reporting
      physical abuse had a significantly earlier age at onset, regardless of their sex
      (V = 0.13, F = 3.11, p = 0.03. Physical abuse predicted an earlier age at onset
      only in women (R2 = 0.23). History of general trauma predicted more frequent
      hospitalizations only in men (R2 = 0.55). CONCLUSIONS: Although women generally
      tend to have a more favorable course of illness including a later age at onset
      men, women with CPA seem to lose this "advantage". It is necessary to investigate
      the contribution of gender interacting with adverse life events in contribution
      to the phenomenology and etiology of schizophrenia.

PMID- 29452965
TI  - Reversal of antiplatelet therapy in traumatic intracranial hemorrhage: Does
      timing matter?
AB  - Reversal of antiplatelet therapy with platelet transfusion in traumatic
      intracranial hemorrhage remains controversial. Several studies have examined this
      topic but few have investigated whether the timing of transfusion affects
      outcomes. Patients admitted to a level 1 trauma center from 1/1/14 to 3/31/16
      with traumatic intracranial hemorrhage taking pre-injury antiplatelet therapy
      were retrospectively analyzed. Patients on concurrent pre-injury anticoagulant
      therapy were excluded. Per institutional guideline, patients on pre-injury
      clopidogrel received 2 doses of platelets while patients on pre-injury aspirin
      received 1 dose of platelets. Patients with worsening hemorrhage defined by an
      increase in the Rotterdam score on follow up CT were compared to those without
      worsening. Mortality, need for neurosurgical intervention, and timing of platelet
      transfusion were analyzed. A total of 243 patients were included with 23 (9.5%)
      having worsening hemorrhage. Patients with worsening hematoma had higher injury
      severity score, head abbreviated injury scale, incidence of subdural hematoma,
      mortality, and lower Glasgow coma scale. There was no significant difference in
      the number of minutes to platelet transfusion between groups. After logistic
      regression analysis the presence of subdural hematoma and lower admission Glasgow
      coma scale were predictors of worsening hematoma, while there remained no
      significant difference in minutes to platelet transfusion. The timing of platelet
      transfusion did not have any impact on rates of worsening hematoma for patients
      with traumatic intracranial hemorrhage on pre-injury antiplatelet therapy.
      Potential risk factors for worsening hematoma in this group are the presence of
      subdural hematoma and lower admission Glasgow coma scale.

PMID- 29452967
TI  - Verrucous carcinoma of the esophagus: A rare entity with a difficult diagnosis.

PMID- 29452968
TI  - Analysis and description of disease-specific quality of life in patients with
      anal fistula.
AB  - INTRODUCTION: In patients diagnosed with anal fistula, knowing the quality of
      life specifically related to the disease can help coloproctology specialists to
      choose the most appropriate therapeutic strategy for each case. The aim of our
      study is to analyzse and describe the factors related to the specific quality of
      life in a consecutive series of patients diagnosed with anal fistula. METHODS:
      Observational, cross-sectional study carried out from March 2015 to February
      2017. All patients were assessed in the colorectal surgery unit of a hospital in
      southeast of Spain. After performing an initial anamnesis and a physical
      examination, patients diagnosed with anal fistula completed the Quality of Life
      in Ppatients with Anal Fistula Questionnaire (QoLAF-Q). This questionnaire
      specifically measures quality of life in people with anal fistula and its score
      range is the following: zero impact = 14 points, limited impact = 15 to 28
      points, moderate impact = 29 to 42 points, high impact = 43 to 56 points, and
      very high impact = 57 to 70 points. RESULTS: A total of 80 patients were
      included. The median score obtained in the questionnaire for the sample studied
      was 34.00 (range=14-68). Statistically significant differences between patients
      with "primary anal fistula" (n=65) and "recurrent anal fistula" (n=15) were
      observed (mean rank=42.96 vs. mean rank=29.83, p=0.048). Furthermore, an inverse
      proportion (P=.016) between "time with clinical symptoms" and "impact on quality
      of life" was found (<6 months: mean rank = 45.55; 6-12 months: mean rank = 44.39;
      1-2 years: mean rank = 37.83; 2-5 years: mean rank = 22; >5 years: mean rank =
      19.00). There were no statistically significant differences (P=.149) between
      quality of life amongst patients diagnosed with complex (mean rank = 36.13) and
      simple fistulae (mean rank = 43.59). CONCLUSIONS: Anal fistulae exert moderate
      high impact on patients' quality of life. "Shorter time experiencing clinical
      symptoms" and the "presence of primary fistula" are factors that can be
      associated with worse quality of life.

PMID- 29452969
TI  - Breast necrosis in a patient with primary T-cell non-Hodgkin lymphoma.

PMID- 29452970
TI  - Effect of tear supplements on signs, symptoms and inflammatory markers in dry
      eye.
AB  - PURPOSE: Three tear supplements were compared for their effects on the signs,
      symptoms and inflammatory status of subjects with dry eye disease. Assessments
      were made before and after both 2 and 4 weeks of treatment. METHODS: In this
      masked, randomized, 3-way crossover trial, eighteen dry eye subjects were
      recruited. At each visit, symptoms, tear evaporation rate, stability and
      osmolarity were measured and tear samples were analyzed for 7 inflammatory
      markers, using multiplex immunoassays. The 3 treatments included
      carboxymethylcellulose-glycerine-castor oil (CGC), carboxymethylcellulose (CMC)
      and hydroxypropyl guar (HPG). The CGC and HPG drops are emulsified lipids; CGC
      also contains osmoprotectants. The CMC drop is a standard aqueous polymeric
      supplement. RESULTS: Significant improvements were seen in symptoms (OSDI) and
      tear stability (NITBUT) with all 3 treatments at 4 weeks. At 4 weeks post-CGC, 6
      out of 7 biomarkers demonstrated a >25% reduction (in 40% of subjects). The same
      reduction (>25%) was seen in 10% of the subjects for CMC and in none of the
      subjects for HPG. No significantly different change to either evaporation rate or
      tear osmolarity was found following any of the three treatments. CONCLUSIONS: In
      this study, the CGC treatment resulted in the greatest reduction in ocular
      biomarkers of inflammation, while all 3 treatments reduced symptoms and improved
      tear stability. These results indicate that subject-perceived symptomatic
      improvements are not necessarily associated with a reduction in objective
      measures of inflammation.

PMID- 29452971
TI  - Medial Overhang of the Tibial Component Is Associated With Higher Risk of
      Inferior Knee Injury and Osteoarthritis Outcome Score Pain After Knee
      Replacement.
AB  - BACKGROUND: The aim of this prospective multicenter study is to investigate the
      association among (1) tibial site-specific overhang of medial, anterior, and
      lateral overhang in relation to Knee Injury and Osteoarthritis Outcome Score pain
      1 year after surgery (1 Y KOOS pain) and (2) the malalignment of TKA components
      including overall malalignment in relation to 1 Y KOOS pain. METHODS: From 10
      centers, across 4 continents, 323 patients were enrolled from October 2011 to
      February 2014. Radiographs were analyzed for tibial overhang on medial, anterior,
      and lateral site and for overall, tibial, femur, and combined malalignment. A 1 Y
      KOOS pain score <70 represented an unsatisfactory pain level. RESULTS: A
      significant association was observed between medial overhang and 1 Y KOOS pain
      with a cut-off of <70 (P = .04), with an odds ratio of 0.46. No significant
      associations were observed among the independent variables of lateral and
      anterior overhang or for overall, tibial, femoral, and combined component
      malalignment, and the dependent variable of 1 Y KOOS pain <70. CONCLUSION: This
      prospective multicenter study showed a significant association between medial
      overhang of the tibial component and a 1 Y KOOS pain <70. The related odds ratio
      was 0.46, which demonstrates that medial overhang may lead to a 54% reduced
      chance for entering an acceptable pain category 1 year after surgery when
      receiving a TKA.

PMID- 29452972
TI  - Does Preoperative Opioid Use Increase the Risk of Early Revision Total Hip
      Arthroplasty?
AB  - BACKGROUND: The purpose of this study is to evaluate the impact of preoperative
      opioid use on the risk of subsequent revison after primary total hip arthroplasty
      (THA). METHODS: The Humana database was queried for unilateral THA between 2007
      2015. Patients were tracked for the occurrence of an ipsilateral revision THA for
      2 years. Factors analyzed included preoperative opioid use (defined as a history
      of opioid prescription filled within 3 months preceding primary THA), age, sex,
      diabetes, anxiety/depression, chronic kidney disease, and obesity (body mass
      index > 30 kg/m2). Multivariate logistic regression analysis was used to
      determine odds ratios. RESULTS: A total of 17,695 primary THA patients were
      analyzed and 0.88% (n = 155) underwent revision THA within 2 years. Preoperative
      opioid use occurred in 36.7% of all. Females comprised 58.7% of the total cohort
      and 80% were >50 years. Preoperative opioid users were significantly more likely
      to undergo early THA revision (1.2% vs 0.7%, P < .001). Other patient factors
      that significantly increased the risk of early THA revision included obesity
      (1.3% vs 0.8%, P = .03) and a preoperative diagnosis of anxiety/depression (1.9%
      vs 0.8%, P = .006). CONCLUSION: Opioid use within 3 months preceding THA
      independently predicts an increased risk of early revision. Additionally,
      independent predictors of early revision include obesity and a diagnosis of
      anxiety/depression. Factors such as these will need to be considered in risk
      adjustment models when assessing quality of care or implementing bundled payment
      initiatives. Further research is needed to evaluate whether discontinuing opioids
      before surgery mitigates this risk.

PMID- 29452973
TI  - The Alpha-Defensin Test for Diagnosing Periprosthetic Joint Infection in the
      Setting of an Adverse Local Tissue Reaction Secondary to a Failed Metal-on-Metal
      Bearing or Corrosion at the Head-Neck Junction.
AB  - BACKGROUND: In patients with adverse local tissue reaction (ALTR) secondary to a
      failed metal-on-metal (MoM) bearing or corrosion at the head-neck junction in a
      metal-on-polyethylene bearing, ruling in or out periprosthetic joint infection
      (PJI) can be challenging. Alpha-defensin has emerged as an accurate test for PJI.
      The purpose of this multicenter, retrospective study was to evaluate the accuracy
      of the alpha-defensin synovial fluid test in detecting PJI in patients with ALTR.
      METHODS: We reviewed medical records of 26 patients from 3 centers with ALTR that
      had an alpha-defensin test performed. Patients were assessed for PJI using the
      Musculoskeletal Infection Society criteria. Thirteen of these subjects had MoM
      total hip arthroplasty, 9 had ALTR secondary to head-neck corrosion, and 4 had
      MoM hip resurfacing. RESULTS: Only 1 of the 26 patients met Musculoskeletal
      Infection Society criteria for infection. However, 9 hips were alpha-defensin
      positive, including 1 true positive and 8 that were falsely positive (31%). All 8
      of the false positives were also Synovasure positive, although 5 of 8 had an
      accompanying warning stating the results may be falsely positive due to a low
      synovial C-reactive protein value. CONCLUSION: Similar to synovial fluid white
      blood cell count, alpha-defensin testing is prone to false-positive results in
      the setting of ALTR. Therefore, we recommend an aggressive approach to ruling out
      PJI including routine aspiration of all hips with ALTR before revision surgery to
      integrate the synovial fluid blood cell count, differential, cultures and
      adjunctive tests like alpha-defensin to allow for accurate diagnosis
      preoperatively.

PMID- 29452974
TI  - The Lawrence D. Dorr Surgical Techniques & Technologies Award: "Running Two
      Rooms" Does Not Compromise Outcomes or Patient Safety in Joint Arthroplasty.
AB  - BACKGROUND: Scrutiny from the federal government and the media regarding the
      safety of 1 surgeon doing cases in 2 operating rooms (ORs) on the same day,
      prompted us to examine our own institutional data. Over the past 11 years,
      surgeons at our facility have operated consecutively in 1 OR on a given day or
      used 2 alternating ORs. This study compares these cases with a focus on revisions
      and complications in both groups. METHODS: Six surgeons performed a total of
      16,916 primary hip and knee arthroplasties from 2006-2016. 7002 cases (41%) were
      consecutive cases (CCs) and 9914 cases (59%) were overlapping cases (OCs).
      Intraoperative complications, component revisions, and postoperative
      complications within 90 days of surgery were compared between the CC and OC
      groups. RESULTS: There was no difference in intraoperative complication rates
      between the two groups (CC 1.6% vs. OC 1.7%, relative risk 1.082, 95% confidence
      interval 0.852 to 1.375, P = .52). There was no difference in 90-day component
      revision rates among the CC and OC groups (0.66% vs. 0.85% respectively, relative
      risk = 1.290, 95% confidence interval 0.901 to 1.845, P = .19). There was also no
      difference in 90-day complication rates among the CC and OC groups (1.33% vs.
      1.45% respectively, relative risk = 1.094, 95% confidence interval 0.844 to
      1.417, P = .54). CONCLUSION: This large study of a single institution with
      multiple surgeons over an 11-year period shows no compromise in patient safety or
      outcomes when comparing cases done in either consecutive or overlapping rooms.

PMID- 29452976
TI  - The Nourish Program: An Innovative Model for Cooking, Gardening, and Clinical
      Care Skill Enhancement for Dietetics Students.

PMID- 29452975
TI  - Associations between Food Security Status and Dietary Inflammatory Potential
      within Lower-Income Adults from the United States National Health and Nutrition
      Examination Survey, Cycles 2007 to 2014.
AB  - BACKGROUND: Evidence suggests both that chronic inflammation mediates the
      association of food insecurity with adverse health outcomes and that diet may be
      a significant source of inflammation among food insecure individuals. OBJECTIVE:
      To examine whether food security status is associated with dietary inflammatory
      potential. DESIGN AND PARTICIPANTS: Cross-sectional data came from the National
      Health and Nutrition Examination Survey (NHANES), cycles 2007 to 2014 (n=10,630).
      The analysis sample is representative of noninstitutionalized US adults with an
      income-to-poverty ratio <=3.00. MAIN OUTCOME: Dietary Inflammatory Index (DII)
      score, calculated using the average of two 24-hour dietary recalls, was the main
      outcome measure. STATISTICAL ANALYSIS: Type III F tests or chi2 tests compared
      population characteristics by food security status, defined using the US Food
      Security Survey Module. Multivariable linear regression was used to estimate the
      association between food security status and the DII score and moderation by
      demographic factors. Survey weighting procedures accounted for the effects of
      stratification and clustering used in the NHANES study design. RESULTS: When
      accounting for socioeconomic status, demographic factors, and health status, DII
      score was higher at greater levels of food insecurity (P=0.0033). Those with very
      low food security had a 0.31 (95% CI=0.12 to 0.49) higher DII score than those
      with high food security. Age moderated the association between food security
      status and DII score (interaction P=0.0103), where the magnitude of the
      association between DII score and severity of food insecurity was higher for
      those >65 years than for younger age groups. CONCLUSION: Food security status may
      be associated with dietary inflammatory potential, which is hypothesized to play
      a role in multiple chronic health conditions. Further research is needed to
      determine the causal nature of this relationship and evaluate how best to
      implement programs designed to address health disparities within food insecure
      populations.

PMID- 29452977
TI  - Arguments Used in Public Comments to Support or Oppose the US Department of
      Agriculture's Minimum Stocking Requirements: A Content Analysis.
AB  - BACKGROUND: In 2016, the US Department of Agriculture (USDA)'s Supplemental
      Nutrition Assistance Program (SNAP) Retailer Rule proposed several changes for
      SNAP-authorized retailers, including: requiring retailers to have at least 85% of
      their food sales come from items that are not cooked or heated on site before or
      after purchase; requiring stores to stock seven varieties of qualifying foods
      from four staple food groups; requiring stores to carry perishable foods in three
      of the four staple groups; requiring stores to carry six units of qualifying
      foods at all times (depth of stock); disqualifying multiple ingredient foods and
      accessory foods from counting toward depth of stock requirements. OBJECTIVES: To
      better understand arguments used to support or oppose the USDA's proposed rule
      that all SNAP-authorized retailers carry more nutritious foods. DESIGN: We
      conducted a qualitative content analysis of a random sample of public comments
      posted to the US Federal Register (a publicly available database) in response to
      the USDA's proposed rule. PARTICIPANTS/SETTING: A random sample of 20% of all
      public comments submitted by individuals and organizations to the US Federal
      Register were analyzed (n=303) for this study. RESULTS: Three main themes were
      discussed: 1) arguments used in opposition to the rule; 2) arguments used in
      support of the rule; and 3) facilitators to assist stores in implementing the
      rule. Some of the subthemes included focusing on definitions used in the rule,
      reduced food access caused by stores leaving the SNAP program, lack of space and
      equipment for healthy foods, and the potential for increasing healthy food
      access. CONCLUSIONS: Nutrition and dietetics practitioners may be tasked with
      working with stores to implement healthy changes. Nutrition and dietetics
      practitioners must understand the role that the USDA has in food policy. In
      addition, understanding how federal food policy influences the environments in
      which dietetics professionals' clients are making food choices is important.

PMID- 29452978
TI  - The management of antibodies in heart transplantation: An ISHLT consensus
      document.
AB  - Despite the successes from refined peri-operative management techniques and
      immunosuppressive therapies, antibodies remain a serious cause of morbidity and
      mortality for patients both before and after heart transplantation. Patients
      awaiting transplant who possess antibodies against human leukocyte antigen are
      disadvantaged by having to wait longer to receive an organ from a suitably
      matched donor. The number of pre-sensitized patients has been increasing, a trend
      that is likely due to the increased use of mechanical circulatory support
      devices. Even patients who are not pre-sensitized can go on to produce donor
      specific antibodies after transplant, which are associated with worse outcomes.
      The difficulty in managing antibodies is uncertainty over which antibodies are of
      clinical relevance, which patients to treat, and which treatments are most
      effective and safe. There is a distinct lack of data from prospective trials. An
      international consensus conference was organized and attended by 103 participants
      from 75 centers to debate contentious issues, determine the best practices, and
      formulate ideas for future research on antibodies. Prominent experts presented
      state-of-the-art talks on antibodies, which were followed by group discussions,
      and then, finally, a reconvened session to establish consensus where possible.
      Herein we address the discussion, consensus points, and research ideas.

PMID- 29452979
TI  - 3-Piece Inflatable Penile Prosthesis Placement Following Radical
      Cystoprostatectomy and Urinary Diversion: Technique and Outcomes.
AB  - BACKGROUND: After radical cystoprostatectomy (RC), postoperative erectile
      dysfunction (ED) is a common consequence with multiple contributing etiologies.
      The inflatable penile prosthesis (IPP) offers patients a definitive treatment
      option when ED is refractory to medical therapies. Because of the hostile
      postoperative anatomy of these patients, a careful surgical approach is necessary
      for successful outcomes and to avoid adjacent organ injury. To date, there is no
      series describing the outcomes of 3-piece IPP placement in patients with urinary
      diversions. AIM: To present contemporary outcomes and a description of our
      technique in placing a 3-piece IPP for postoperative ED in patients with a
      history of RC with orthotopic neobladder, ileal conduit, or continent cutaneous
      diversion. METHODS: We retrospectively reviewed 80 patients who underwent primary
      placement of a 3-piece IPP (AMS 700; American Medical Systems Inc, Minnetonka,
      MN, USA) after RC and urinary diversion from 2003 through 2016. 79 patients
      underwent RC in their treatment of urologic malignancy (71 for bladder cancer, 8
      for prostate cancer) and 1 underwent RC for refractory interstitial cystitis. An
      infrapubic approach was used in most patients, with reservoir placement in the
      lateral retroperitoneal space through a counterincision medial to the anterior
      superior iliac spine. Patient demographics, perioperative data, and postoperative
      outcomes including prosthetic infection and mechanical failure were examined and
      statistical analysis was performed. OUTCOMES: Rates of device infection, revision
      surgery, and reservoir complications. RESULTS: After mean follow-up of 53.9
      months (6.5-150.7 months), 4 patients developed infection of the prosthesis that
      required explantation. 3 of those patients underwent successful IPP
      reimplantation. 5 patients required revision surgery (pump replacement, n = 3;
      pump relocation, n = 1; cylinder replacement for cylinder aneurysm, n = 1) for
      mechanical failure. No statistically significant associations were found between
      infection and comorbidities, urinary diversion, exposure to chemotherapy,
      radiation, or presence of an artificial urinary sphincter. CLINICAL IMPLICATIONS:
      The 3-piece IPP is an effective treatment option for medication-refractory ED
      that can be placed safely in patients with all forms of urinary diversion.
      STRENGTHS AND LIMITATIONS: This study represents the 1st series that describes a
      successful technique and long-term outcomes of patients with urinary diversion.
      It is limited by its single-surgeon, single-center experience and lacks validated
      patient satisfaction data in follow-up. CONCLUSIONS: The 3-piece IPP, with
      reservoir placement in the lateral retroperitoneum, can be implanted successfully
      in patients with all forms of urinary diversion without a significant increase in
      infectious complications, reservoir erosion, or mechanical failure. Loh-Doyle J,
      Patil MB, Sawkar H, et al. 3-Piece Inflatable Penile Prosthesis Placement
      Following Radical Cystoprostatectomy and Urinary Diversion: Technique and
      Outcomes. J Sex Med 2018;15:907-913.

PMID- 29452980
TI  - Association between smoking cessation and weight gain in treatment-seeking
      African Americans.
AB  - INTRODUCTION: Research has shown that African Americans gain more than average
      weight after smoking cessation. However, African Americans have been
      underrepresented in post-cessation weight gain research. The current study
      examined 1) the pattern of weight gain and 2) the association between smoking
      status and weight gain in a sample of African Americans seeking smoking cessation
      treatment. METHODS: Data were drawn from a randomized controlled trial testing
      the efficacy of a 4-week culturally specific smoking cessation cognitive
      behavioral therapy (CBT) intervention among African American smokers (N = 342).
      Weight was measured and self-reported smoking status was biochemically verified
      at baseline, end of counseling, 3-, 6-, and 12-month follow-ups. Random effects
      multilevel modeling was used to examine weight gain over twelve months post CBT,
      and a fully unconditional model tested the pattern of weight gain over time.
      Smoking status was included as a time-varying factor to examine its effect on
      weight gain, controlling for potential confounding variables. RESULTS: Weight
      significantly increased among those who remained abstinent over 12 months post
      CBT [average gain of seven lbs. (three kg)]. Controlling for covariates,
      abstinence was predictive of the rate of weight gain for those with high weight
      concern. CONCLUSIONS: Weight gain among African American abstainers was
      comparable to the average post-cessation weight gain observed among the general
      population. It is possible that exposure to CBT (culturally specific or standard)
      may have mitigated excessive weight gain. Future research should assess
      predictors of weight gain in African American smokers to inform future smoking
      cessation interventions and help elucidate factors that contribute to tobacco-
      and obesity-related health disparities.

PMID- 29452981
TI  - Body mass index and tobacco-product use among U.S. youth: Findings from wave 1
      (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study.
AB  - INTRODUCTION: Tobacco and obesity are leading contributors to mortality in the
      United States. Due to emerging changes in youth tobacco use, further examination
      of co-occurrence of these issues is warranted. METHODS: This study examined
      associations between body mass index (BMI) and tobacco-product use and whether
      these varied by gender in a nationally representative sample of 12,416 Wave 1
      (2013-2014) U.S. youth (12-17 years) from the Population Assessment of Tobacco
      and Health Study. Multivariable logistic regression analyses examined the odds of
      past 30-day tobacco-product use according to BMI. BMI was analyzed categorically
      using the Centers for Disease Control and Prevention (CDC) BMI-for-age weight
      status categories (underweight/healthy weight, overweight, and obese) and as a
      continuous variable. RESULTS: Youth classified as overweight or obese were not
      more likely to use any tobacco, cigarettes, e-cigarettes, any cigar, or hookah.
      However, youth who were obese were more likely to use smokeless tobacco (Adjusted
      Odds Ratio (AOR) = 1.68, 95% Confidence Interval (CI): 1.01, 2.81). There were no
      significant gender interactions for these associations. When BMI was analyzed
      continuously, a 5-unit and 10-unit increase was significantly associated with
      using any tobacco, cigarettes, any cigar, and smokeless tobacco. This linear
      association was supported by similar results for a log-transformed BMI variable.
      CONCLUSIONS: Findings suggest a continuum between weight increase and tobacco
      product use among American youth. Clinicians should consider screening for
      tobacco use among youth who gain weight within any weight class, not just those
      considered overweight or obese.

PMID- 29452982
TI  - Reactive Oxygen Species: Involvement in T Cell Signaling and Metabolism.
AB  - T cells are a central component of defenses against pathogens and tumors. Their
      effector functions are sustained by specific metabolic changes that occur upon
      activation, and these have been the focus of renewed interest. Energy production
      inevitably generates unwanted products, namely reactive oxygen species (ROS),
      which have long been known to trigger cell death. However, there is now evidence
      that ROS also act as intracellular signaling molecules both in steady-state and
      upon antigen recognition. The levels and localization of ROS contribute to the
      redox modeling of effector proteins and transcription factors, influencing the
      outcome of the T cell response. We discuss here how ROS can directly fine-tune
      metabolism and effector functions of T cells.

PMID- 29452983
TI  - Orchestration of NLRP3 Inflammasome Activation by Ion Fluxes.
AB  - The assembly of the NLRP3 inflammasome can promote the release of IL-1beta/IL-18
      and initiate pyroptosis. Accordingly, the dysregulation of NLRP3 inflammasome
      activation is involved in a variety of human diseases, including gout, diabetes,
      and Alzheimer's disease. NLRP3 can sense a variety of structurally unrelated
      pathogen-associated molecular patterns (PAMPs) or danger-associated molecular
      patterns (DAMPs) to trigger inflammation, but the unifying mechanism of NLRP3
      activation is still poorly understood. Increasing evidence suggests that
      intracellular ions, such as K+, Ca2+, and Cl-, have a significant role in NLRP3
      inflammasome activation. Here, we review the current knowledge about the role of
      ionic fluxes in NLRP3 inflammasome activation and discuss how disturbances in
      intracellular ionic levels orchestrate different signaling events upstream of
      NLRP3.

PMID- 29452984
TI  - Quantitative cerebrovascular pathology in a community-based cohort of older
      adults.
AB  - Cerebrovascular disease, especially small vessel pathology, is the leading
      comorbidity in degenerative disorders. We applied arterial spin labeling and
      cerebrovascular reserve (CVR) imaging to quantify small vessel disease and study
      its effect on cognitive symptoms in nondemented older adults from a community
      based cohort. We evaluated baseline cerebral blood flow (CBF) using arterial spin
      labeling and percent signal change as a marker of CVR using blood-oxygen level
      dependent imaging following a breath-hold stimulus. Measurements were performed
      in and near white matter hyperintensities, which are currently the standard to
      assess severity of vascular pathology. We show that similar to other studies (1)
      CBF and CVR are markedly reduced in the hyperintensities as well as in the tissue
      surrounding them, indicating susceptibility to infarction; (2) low CBF and CVR
      are significantly correlated with poor cognitive performance; and (3) in
      addition, compared to a 58.4% reduction in CBF, larger exhaustion (79.3%) of CVR
      was observed in the hyperintensities with a faster, nonlinear rate of decline. We
      conclude that CVR may be a more sensitive biomarker of small vessel disease than
      CBF.

PMID- 29452985
TI  - Effectiveness of two home ergonomic programs in reducing pain and enhancing
      quality of life in informal caregivers of post-stroke patients: A pilot
      randomized controlled clinical trial.
AB  - BACKGROUND: Informal caregivers of post-stroke patients usually undergo high
      levels of pain and stress and have a reduced quality of life. OBJECTIVE: To
      evaluate the effectiveness of two home ergonomic interventions aimed at reducing
      pain intensity and perceived stress and enhancing the quality of life in informal
      caregivers of chronic post-stroke patients. METHODS: A randomized single-blind
      controlled clinical trial was conducted, with a sample of 33 informal caregivers
      of patients with stroke. Three groups were included: one received postural
      hygiene training and kinesiotherapy, for 12 weeks, two days a week, one hour per
      session; another received adaptation of the home environment, and the third was a
      control group. Pain intensity, stress level and general quality of life were
      evaluated at three-time points: pre-intervention, post-intervention, and after a
      follow-up period of three months. RESULTS: Neck pain decreased in the two
      experimental groups, and increased in the control group. Pain in the shoulders
      and knees was alleviated in the group that received postural hygiene and
      kinesiotherapy. In addition, regarding quality of life, this group obtained an
      improvement in the physical health dimension, while the home adaptation group
      reported improved social relationships. CONCLUSIONS: These results suggest that
      12 weeks of training in postural hygiene, combined with kinesiotherapy, and home
      adaptations can reduce pain and improve several aspects of the quality of life of
      this population. CLINICALTRIALS. GOV ID: NCT03284580.

PMID- 29452986
TI  - The psychological consequences of violence against people with disabilities.
AB  - BACKGROUND: People with disabilities experience mental health disparities and
      higher rates of violence compared to people without disabilities. Few studies
      have examined the psychological consequences of violence against people with
      disabilities, and whether they differ from those experienced by people without
      disabilities. OBJECTIVE: This study compared psychological consequences of
      violence among men and women with and without disabilities. METHODS: We analyzed
      data from the 2008-2014 waves of the National Crime Victimization Survey.
      Multiple logistic regressions were estimated to compare the psychological impact
      of violent crime on respondents without disabilities to those with disabilities,
      who comprised roughly 20% of the sample (n = 8,070). We stratified by gender to
      compare the effects of violence experienced by men and women. RESULTS: Men with
      disabilities were more likely than men without disabilities to report severe
      distress (AOR = 2.07, p < 0.001), anxiety (1.79, p < 0.001), depression (2.32, p
      < 0.001), and anxiety and depression (2.34; p < 0.001), but were less likely to
      experience each outcome compared to women with disabilities. Men with
      disabilities had similar odds of adverse psychological outcomes compared to women
      without disabilities. Women with disabilities had higher odds of severe distress
      following violence compared to men without disabilities (3.90, p < 0.001) or
      women without disabilities (1.86, p < 0.001). Similarly, women with disabilities
      had higher odds of anxiety, depression, and anxiety and depression compared to
      men and women without disabilities. CONCLUSIONS: Women with disabilities are at
      higher risk of negative psychological consequences resulting from violence
      compared to other gender-disability groups. Men with disabilities also experience
      worse outcomes relative to men without disabilities.

PMID- 29452987
TI  - Cell therapy for peripheral artery disease.
AB  - Patients with severe peripheral artery disease (PAD) who are not candidates for
      revascularization have poor prognosis. Cell therapy using peripheral blood
      derived or bone marrow-derived mononuclear cells, mesenchymal stem cells, or
      marker-specific subsets of bone marrow cells with angiogenic properties may hold
      promise for no-option PAD patients. Injected cells may exert beneficial actions
      by enhancing local angiogenesis (either through maturation of endothelial
      progenitors, or through secretion of angiogenic mediators), or by transducing
      cytoprotective signals that preserve tissue structure. Despite extensive
      research, robust clinical evidence supporting the use of cell therapy in patients
      with critical limb ischemia is lacking. Larger, well-designed placebo-controlled
      clinical trials did not support the positive results of smaller less rigorous
      studies. There is a need for high-quality clinical studies to test the
      effectiveness of cell therapy in PAD patients. Moreover, fundamental cell
      biological studies are needed to identify the optimal cell types, and to develop
      strategies that may enhance homing, survival and effectiveness of the injected
      cells.

PMID- 29452988
TI  - Expert consensus recommendations on the cardiogenetic care for patients with
      thoracic aortic disease and their first-degree relatives.
AB  - BACKGROUND: Thoracic aortic aneurysm (TAA) is a potentially life-threatening
      disorder with a strong genetic component. The number of genes implicated in TAA
      has increased exponentially over the last decade. Approximately 20% of patients
      with TAA have a positive family history. As most TAA remain asymptomatic for a
      long time, screening of at risk relatives is warranted to prevent complications.
      Existing international guidelines lack detailed instructions regarding genetic
      evaluation and family screening of TAA patients. We aimed to develop a consensus
      document to provide medical guidance for all health care professionals involved
      in the recognition, diagnosis and treatment of patients with thoracic aortic
      disease and their relatives. METHODS: A multidisciplinary panel of experts
      including cardiologists, cardiothoracic surgeons, clinical geneticists and
      general practitioners, convened to review and discuss the current literature,
      guidelines and clinical practice on genetic testing and family screening in TAA.
      RESULTS: There is a lack of high-quality evidence in the literature. This
      consensus statement, based on the available literature and expert opinions,
      summarizes our recommendations in order to standardize and optimize the
      cardiogenetic care for patients and families with thoracic aortic disease. In
      particular, we provide criteria to identify those patients most likely to have a
      genetic predisposition, and discuss the preferred modality and frequency of
      screening in their relatives. CONCLUSIONS: Age, family history, aortic size and
      syndromic features determine who is advised to have genetic testing as well as
      screening of first-degree relatives. There is a need for more prospective
      multicenter studies to optimize current recommendations.

PMID- 29452989
TI  - Prognostic role of cardiac calcifications in primary prevention: A powerful
      marker of adverse outcome highly dependent on underlying cardiac rhythm.
AB  - BACKGROUND: Increasing evidence exists regarding calcium detected in aortic cusps
      and/or mitral annulus (AOC_MAC) at transthoracic echocardiogram as a predictor of
      cardiovascular (CV) events and mortality. PURPOSE: To verify whether AOC_MAC has
      a prognostic role in the setting of primary prevention independently of the
      presence of atrial fibrillation (AF). METHODS: All subjects consecutively
      referred from January 2011 to October 2014 to the Cardiovascular Centre for CV
      risk assessment in primary prevention were selected. AOC_MAC was assessed by
      transthoracic echocardiography. Primary study endpoint was a composite of CV
      hospitalizations/all-cause death. RESULTS: The 1389 study patients were 70 years
      old, 43% males, 24% had diabetes mellitus, 75% arterial hypertension, 56%
      dyslipidaemia. Of all, 997 (72%) were in sinus rhythm (SR), 392 (28%) in AF.
      Patients with AF were older and more frequently males, with larger atria than SR
      subjects. During a median follow-up of 32 months, 165 patients (12%) were
      hospitalized for CV cause, 68 (5%) died. The primary endpoint occurred more
      frequently in patients with than without AOC_MAC (18% vs 11%, p < 0.001). AF
      patients showed higher event-rate compared with patients in SR (20% vs 10%,
      respectively; p < 0.01). AOC_MAC emerged as an independent prognosticator of
      primary endpoint in SR patients (HR 1.74 [1.07-2.82], p = 0.02), together with
      increasing age and left ventricular hypertrophy, while AOC_MAC had no prognostic
      relevance in AF patients. CONCLUSIONS: In subjects with multiple CV risk factors
      assessed in primary prevention, the presence of AF nullifies the prognostic power
      of AOC_MAC, on the contrary robustly confirmed in SR patients.

PMID- 29452990
TI  - Corrigendum to "The prevention of statins against AKI and mortality following
      cardiac surgery: A meta-analysis" [Int. J. Cardiol. 222 (Nov 1 2016) 260-6].

PMID- 29452991
TI  - Relationship between Pregnancy-associated Plasma Protein-A and tissue factor
      levels in the coronary circulation of patients with acute coronary syndrome.

PMID- 29452992
TI  - Activity of ceftobiprole against Staphylococcus spec. isolates derived from
      foreign body associated infections.
AB  - Antibiotic therapy is essential in foreign body associated infections. The
      treatment regime should aim at high tissue concentrations, high bioavailability,
      high biofilm penetration and good tolerance. We investigated whether the new
      cephalosporin ceftobiprole is active against clinical isolates from
      musculoskeletal foreign body associated infections. One hundred ninety-six
      staphylococci isolates (coagulase negative staphylococci and Staphylococcus
      aureus) derived from foreign body associated infections were tested towards
      susceptibility to ceftobiprole, using a test strip assay and broth microdilution.
      The MIC for all strains S. aureus indicated susceptibility to ceftobiprole. The
      MIC of only two strains of coagulase negative staphylococci was above 2 mg/L. Our
      results show that ceftobiprole might be considered as an off-label treatment
      option in foreign body associated infections.

PMID- 29452993
TI  - An in vitro evaluation of the efficacy of tedizolid: implications for the
      treatment of skin and soft tissue infections.
AB  - Skin and soft tissue infections (SSTI) are among the most commonly occurring
      infections and evidence suggests that these are increasing world-wide. The
      aetiology is diverse, but Staphylococcus aureus predominate and these are often
      resistant to antimicrobials that were previously effective. Tedizolid is a new
      oxazolidinone-class antibacterial indicated for the treatment of adults with SSTI
      caused by Gram-positive pathogens, including S. aureus. The aim of this study was
      to evaluate the in vitro efficacy of tedizolid in comparison to other clinically
      used antibacterials against antibiotic sensitive- and resistant-staphylococci,
      grown in planktonic cultures and as biofilms reflecting the growth of the
      microorganism during episodes of SSTI. Against a panel of 66 clinical
      staphylococci, sensitivity testing revealed that a lower concentration of
      tedizolid was required to inhibit the growth of staphylococci compared to
      linezolid, vancomycin and daptomycin; with the tedizolid MIC50 being 8-fold (S.
      aureus) or 4-fold (S. epidermidis) below that obtained for linezolid. In
      addition, cfr+ linezolid-resistant strains remained fully susceptible to
      tedizolid. Against S. aureus biofilms, 10*MIC tedizolid was superior or
      comparable with 10*MIC comparator agents in activity, and superior to 10*MIC
      linezolid against those formed by S. epidermidis (65 vs. 33% reduction,
      respectively). Under flow-conditions both oxazolidinones at 10*MIC statistically
      out-performed vancomycin in their ability to reduce the viable cell count within
      a S. aureus biofilm with fewer the 12% of cells surviving compared to 63% of
      cells. In conclusion, tedizolid offers a realistic lower-dose alternative agent
      to treat staphylococcal SSTI, including infections caused by multi-drug resistant
      strains.

PMID- 29452994
TI  - Transmission routes of respiratory viruses among humans.
AB  - Respiratory tract infections can be caused by a wide variety of viruses. Airborne
      transmission via droplets and aerosols enables some of these viruses to spread
      efficiently among humans, causing outbreaks that are difficult to control. Many
      outbreaks have been investigated retrospectively to study the possible routes of
      inter-human virus transmission. The results of these studies are often
      inconclusive and at the same time data from controlled experiments is sparse.
      Therefore, fundamental knowledge on transmission routes that could be used to
      improve intervention strategies is still missing. We here present an overview of
      the available data from experimental and observational studies on the
      transmission routes of respiratory viruses between humans, identify knowledge
      gaps, and discuss how the available knowledge is currently implemented in
      isolation guidelines in health care settings.

PMID- 29452941
TI  - Surgical site infection after gastrointestinal surgery in high-income, middle
      income, and low-income countries: a prospective, international, multicentre
      cohort study.
AB  - BACKGROUND: Surgical site infection (SSI) is one of the most common infections
      associated with health care, but its importance as a global health priority is
      not fully understood. We quantified the burden of SSI after gastrointestinal
      surgery in countries in all parts of the world. METHODS: This international,
      prospective, multicentre cohort study included consecutive patients undergoing
      elective or emergency gastrointestinal resection within 2-week time periods at
      any health-care facility in any country. Countries with participating centres
      were stratified into high-income, middle-income, and low-income groups according
      to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1
      study and other studies that have been found to affect the likelihood of SSI were
      entered into risk adjustment models. The primary outcome measure was the 30-day
      SSI incidence (defined by US Centers for Disease Control and Prevention criteria
      for superficial and deep incisional SSI). Relationships with explanatory
      variables were examined using Bayesian multilevel logistic regression models.
      This trial is registered with ClinicalTrials.gov, number NCT02662231. FINDINGS:
      Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for
      analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339
      (58.5%) patient were from high-HDI countries (193 hospitals in 30 countries),
      3918 (31.2%) patients were from middle-HDI countries (82 hospitals in 18
      countries), and 1282 (10.2%) patients were from low-HDI countries (68 hospitals
      in 18 countries). In total, 1538 (12.3%) patients had SSI within 30 days of
      surgery. The incidence of SSI varied between countries with high (691 [9.4%] of
      7339 patients), middle (549 [14.0%] of 3918 patients), and low (298 [23.2%] of
      1282) HDI (p<0.001). The highest SSI incidence in each HDI group was after dirty
      surgery (102 [17.8%] of 574 patients in high-HDI countries; 74 [31.4%] of 236
      patients in middle-HDI countries; 72 [39.8%] of 181 patients in low-HDI
      countries). Following risk factor adjustment, patients in low-HDI countries were
      at greatest risk of SSI (adjusted odds ratio 1.60, 95% credible interval 1.05
      2.37; p=0.030). 132 (21.6%) of 610 patients with an SSI and a microbiology
      culture result had an infection that was resistant to the prophylactic antibiotic
      used. Resistant infections were detected in 49 (16.6%) of 295 patients in high
      HDI countries, in 37 (19.8%) of 187 patients in middle-HDI countries, and in 46
      (35.9%) of 128 patients in low-HDI countries (p<0.001). INTERPRETATION: Countries
      with a low HDI carry a disproportionately greater burden of SSI than countries
      with a middle or high HDI and might have higher rates of antibiotic resistance.
      In view of WHO recommendations on SSI prevention that highlight the absence of
      high-quality interventional research, urgent, pragmatic, randomised trials based
      in LMICs are needed to assess measures aiming to reduce this preventable
      complication. FUNDING: DFID-MRC-Wellcome Trust Joint Global Health Trial
      Development Grant, National Institute of Health Research Global Health Research
      Unit Grant.

PMID- 29452996
TI  - Nomogram for Predicting the Risk of Invasive Pulmonary Adenocarcinoma for Pure
      Ground-Glass Nodules.
AB  - BACKGROUND: The pure ground-glass nodule is a common clinical concern. The
      purpose of this study was to develop a nomogram to predict the risk of invasive
      pulmonary adenocarcinoma in patients with pure ground-glass nodules 1 cm or less
      in diameter based on the computed tomography imaging features. METHODS: We
      reviewed a total of 250 patients who had undergone resection of pure ground-glass
      nodules 1 cm or less in diameter in our hospital, including the data of
      histopathologic examinations after surgical resection. Clinical information and
      imaging features were analyzed by the use of univariable and multivariable
      logistic regression analysis. A nomogram to predict the risk of invasive
      pulmonary adenocarcinoma was developed, and the calibration curves for the
      probability were drawn. RESULTS: Two hundred fifty patients were enrolled for
      analysis: 13 as having benign lesions, 8 as atypical adenomatous hyperplasia, 64
      as adenocarcinoma in situ, 137 as minimally invasive adenocarcinoma, and 28 as
      invasive adenocarcinoma. On the basis of the final regression analysis, the
      lesion size, spiculation, lobulation, air bronchogram, vascular convergence,
      pleural tag, and the computed tomography window width were identified and were
      entered into the nomogram. The nomogram showed an excellent discrimination, with
      an area under the receiver operating characteristics curve of 0.916 for internal
      validation and 0.970 for external validation. The calibration curves for the
      probability of invasive pulmonary adenocarcinoma showed optimal agreement between
      the predicted probability by the nomogram and the actual probability.
      CONCLUSIONS: We constructed a novel nomogram that can predict the risk of
      invasive pulmonary adenocarcinoma for patients with pure ground-glass nodules 1
      cm or less in diameter. With highly accurate, excellent calibration and
      discrimination of the model, clinicians could more precisely make a specific
      treatment strategy for each patient.

PMID- 29452995
TI  - Immune barriers of Ebola virus infection.
AB  - Since its initial emergence in 1976 in northern Democratic Republic of Congo
      (DRC), Ebola virus (EBOV) has been a global health concern due to its virulence
      in humans, the mystery surrounding the identity of its host reservoir and the
      unpredictable nature of Ebola virus disease (EVD) outbreaks. Early after the
      first clinical descriptions of a disease resembling a 'septic-shock-like
      syndrome', with coagulation abnormalities and multi-system organ failure,
      researchers began to evaluate the role of the host immune response in EVD
      pathophysiology. In this review, we summarize how data gathered during the last
      40 years in the laboratory as well as in the field have provided insight into
      EBOV immunity. From molecular mechanisms involved in EBOV recognition in infected
      cells, to antigen processing and adaptive immune responses, we discuss current
      knowledge on the main immune barriers of infection as well as outstanding
      research questions.

PMID- 29452997
TI  - Long-Term Outcomes of Total Anomalous Pulmonary Venous Drainage Repair in
      Neonates and Infants.
AB  - BACKGROUND: Outcomes of operations for total anomalous pulmonary venous drainage
      (TAPVD) have improved. However, operations in the neonatal period and the
      development of postoperative pulmonary venous obstruction are associated with a
      high mortality rate. METHODS: A retrospective review was conducted for all
      neonates and infants (n = 214) who underwent operations for isolated TAPVD (1973
      to 2014). RESULTS: Median age was 18 days (1 day to 1 year). There were 17 (7.9%)
      early deaths. Risk factors for early death were prolonged cardiopulmonary bypass
      time (p = 0.005) and neonatal age at the operation (p = 0.048). Early mortality
      was 2.5% for infants (n = 81) and 11% for neonates (n = 133; p = 0.021) during
      the entire study period. Hospital deaths for neonates remained unchanged during
      the four eras of 1973 to 1988, 1989 to 1998, 1999 to 2008, and 2009 to 2014.
      Survival at 10 and 20 years was 88% +/- 2.2% (95% confidence interval, 82% to
      91%). Reoperation for postoperative pulmonary venous obstruction was required in
      22 patients (10%). Risk factors for reoperation were prolonged cardiopulmonary
      bypass time (p = 0.015), lower operative weight (p = 0.003), and an episode of
      postoperative pulmonary hypertensive crisis (p = 0.005). Freedom from reoperation
      at 20 years was 86% +/- 3.2% (95% confidence interval, 78% to 91%). All survivors
      were asymptomatic at a mean of 13 +/- 9 years (range, 1 month to 42 years) after
      the operation. CONCLUSIONS: Although isolated TAPVD repair in infants can be
      performed without death, the operation is associated with a high mortality rate
      in neonates that remained unchanged during the long study period. Survival beyond
      1 year after the operation is associated with excellent long-term outcomes.

PMID- 29452999
TI  - Chylothorax as a Risk Factor for Thrombosis in Adults: A Proof-of-Concept Study.
AB  - BACKGROUND: Postoperative chylothorax in children is associated with an increased
      risk of vascular thrombosis, hypothesized to be from loss of antithrombin into
      chylous fluid resulting in a hypercoagulable state. In adults, an increased
      thrombotic risk with chylothorax has not been described. Adults undergoing Ivor
      Lewis esophagogastrectomy have two strong thrombotic risk factors-active
      malignancy and postoperative state-allowing for relative homogeneity in baseline
      thrombotic risk; therefore, we studied the association of chylothorax with
      thrombosis in this population. METHODS: We performed a single-center
      retrospective cohort study at a tertiary care academic center. Patients included
      adults undergoing Ivor-Lewis esophagogastrectomy between January 1, 2006, and
      December 31, 2012. We collected demographics, pleural fluid characteristics, and
      relevant imaging within 30 days after the operation. Using nominal logistic
      regression, we studied the effects of chylothorax, age, sex, body mass index,
      American Society of Anesthesiologists Physical Status Classification, operative
      duration, and hospital length of stay on the incidence of postoperative
      thrombosis. RESULTS: We identified 608 patients who underwent Ivor-Lewis
      esophagogastrectomy. Of these, 524 (86.2%) had no pleural fluid analysis, 48
      (7.9%) had nonchylous effusions, and 36 (5.9%) had chylothoraces, with incident
      acute vascular thrombosis within 30 days postoperatively occurring in 22 of 524
      (4.2%), 2 of 48 (4.2%), and 8 of 36 (22.2%), respectively (p = 0.001). In
      multivariate analyses, after adjusting for the above factors, chylothorax was
      associated with significantly higher odds of any vascular thrombosis (odds ratio,
      5.46; p = 0.0013) and deep venous thrombosis/pulmonary embolism (odds ratio,
      6.76; p = 0.0016). CONCLUSIONS: Chylothorax is associated with a significantly
      higher incidence of vascular thrombosis in adults undergoing Ivor-Lewis
      esophagogastrectomy. Vascular thrombosis was associated with a significantly
      higher 90-day mortality rate.

PMID- 29452998
TI  - Resection of Intrathoracic Paraganglioma With and Without Cardiopulmonary Bypass.
AB  - BACKGROUND: Intrathoracic paragangliomas (PGLs) are rare tumors. Approximately
      50% originate from and around cardiac structures. METHODS: A retrospective review
      was made of the perioperative course of patients with intrathoracic PGL resection
      from 2000 through 2015 at Mayo Clinic in Rochester, Minnesota. RESULTS: Twenty
      two patients underwent PGL resection. Sixteen patients (73%) had functioning
      tumors (11, noradrenergic; 4, mixed noradrenergic and dopaminergic; 1,
      dopaminergic). Patients with functioning tumors received preoperative adrenergic
      blockade: 15 (68%), alpha1,2-adrenergic receptor antagonist; 4 (18%), alpha1
      adrenergic receptor antagonists; and 13 (59%) metyrosine. Six patients with
      nonfunctioning tumors had no adrenergic blockade. Twelve patients had tumor
      resection without cardiopulmonary bypass-9 for PGL associated with the great
      vessels, 2 for PGL with pericardial involvement, and 1 for PGL in right
      atrioventricular groove. Ten patients required cardiopulmonary bypass; for 9, the
      tumor involved cardiac structures and for 1, it involved ascending aorta and
      proximal aortic arch. Of these, 1 patient had uncontrollable bleeding and died
      intraoperatively. Other than this single death, there were no inhospital major
      cardiac or pulmonary complications. Median follow-up was 8.2 years (range, 2.1 to
      17.2). Six patients subsequently had metastatic disease, and of them, 1 died 6
      years after the operation. CONCLUSIONS: In this series, 73% of intrathoracic PGLs
      were functional and involved noradrenergic, mixed noradrenergic and dopaminergic,
      or pure dopaminergic secretion. Cardiac and pericardial paraganglioma resection
      may require cardiopulmonary bypass. Although intraoperative bleeding in most
      complex cases may be uncontrollable, as for 1 of our patients, those who survived
      hospital discharge had favorable long-term outcomes.

PMID- 29453000
TI  - Neoadjuvant Chemoradiation Shows No Survival Advantage to Chemotherapy Alone in
      Stage IIIA Patients.
AB  - BACKGROUND: For operable patients with clinical stage IIIA non-small cell lung
      cancer, the optimum neoadjuvant treatment strategy remains unclear. Our aim was
      to compare perioperative and long-term outcomes for patients receiving
      neoadjuvant chemoradiotherapy (NCRT) versus neoadjuvant chemotherapy (NCT) alone.
      METHODS: We queried the National Cancer Database to identify all patients with N2
      and either T1-T2 non-small cell lung cancer who received either NCRT or NCT
      followed by lobectomy between 2006 and 2012. Patients with T3 tumors were
      excluded. A propensity match analysis was performed incorporating preoperative
      variables, and the incidence of postoperative complications, pathologic
      downstaging, and long-term survival were compared. RESULTS: In all, 1,936
      patients met criteria, 745 NCT and 1,191 NCRT. The NCRT patients were younger,
      less likely to be treated at an academic medical center, and more likely to have
      adenocarcinoma. After propensity matching, patients in the NCT group showed lower
      30-day mortality (1.3% versus 2.9%) and 90-day mortality (2.9% versus 6.0%), and
      were more likely to undergo a minimally invasive resection (25.7% versus 14.1%).
      The NCRT patients were more likely to have a pathologic complete response (14.2%
      versus 4.0%) and to be N0 at the time of resection (45.2% versus 38.7%). In the
      multivariable analysis, NCRT patients were at a greater risk of mortality than
      NCT patients (hazard ratio 1.18, 95% confidence interval: 1.03 to 1.36).
      CONCLUSIONS: In our cohort, combined neoadjuvant chemotherapy and radiation
      therapy was associated with improved pathologic downstaging but showed increased
      perioperative mortality with no improvement in long-term overall survival. For
      stage IIIA patients with smaller tumors without local invasion, chemotherapy
      alone may be the preferred neoadjuvant treatment.

PMID- 29453001
TI  - Transmitral Septal Myectomy for Hypertrophic Obstructive Cardiomyopathy.
AB  - BACKGROUND: Intrinsic abnormalities of the mitral valve are common in patients
      with hypertrophic cardiomyopathy and may need to be addressed at operation.
      METHODS: Consecutive patients undergoing transmitral septal myectomy were
      retrospectively reviewed. The ventricular septum was exposed through a left
      atriotomy, and the anterior leaflet of the mitral valve was detached from its
      annulus. An extended myectomy was performed to the base of the papillary muscles.
      After myectomy, the anterior leaflet was reattached and concomitant mitral valve
      repair or replacement was performed. In some cases, we performed a modified
      anterolateral commissural closure suture, which served to reposition the lateral
      aspect of the anterior leaflet out of the left ventricular outflow tract
      ("curtain stitch"). RESULTS: Twenty patients who underwent this procedure were
      identified (70% women; mean age 63 years). Mitral regurgitation was moderate in
      55% and severe in 40%. Preoperative peak left ventricular outflow tract gradient
      was 92 +/- 43 mm Hg. Mitral valve repair (n = 11) or replacement (n = 9) was
      performed. Predischarge transthoracic echocardiography demonstrated a left
      ventricular outflow tract gradient of 10 +/- 5 mm Hg. There was no operative
      mortality. Follow-up was 100% complete and averaged 22 +/- 25 months. No patient
      required reoperation, and there was no recurrence of left ventricular outflow
      tract obstruction or mitral regurgitation greater than mild. CONCLUSIONS:
      Potential advantages of transmitral myectomy include a panoramic view of the
      septum and mitral subvalvular apparatus and the ability to simultaneously address
      mitral valve pathology. Consideration should be given to using the transmitral
      approach to septal myectomy as the preferred approach for the surgical treatment
      of hypertrophic cardiomyopathy.

PMID- 29453002
TI  - Operative Outcomes of Multiple-Arterial Versus Single-Arterial Coronary Bypass
      Grafting.
AB  - BACKGROUND: More than 90% of coronary artery bypass grafting (CABG) is performed
      with a single-arterial bypass graft (SABG), based on the left internal thoracic
      artery (ITA) with supplemental vein grafts. This practice, often justified by
      safety concerns with multiple-arterial grafting (MABG), defies evidence of
      improved late survival achieved with bilateral ITA (BITA-MABG) or left ITA plus
      radial artery (RA-MABG). We hypothesized that MABG and SABG are equally safe.
      METHODS: We analyzed The Society of Thoracic Surgeons National Database (2004 to
      2015) to assess the operative safety of BITA-MABG (n = 73,054) and RA-MABG (n =
      97,623) vs SABG (n = 1,334,511). Primary end points were operative (30-day or
      same hospitalization) mortality (OM) and deep sternal wound infections (DSWI).
      Risk-adjusted odds ratios (AOR) and 95% confidence intervals (CIs) were derived
      from by logistic regression with sensitivity analyses in multiple subcohorts
      including MABG use rate. RESULTS: SABG (73.8% men; median age, 66 years), BITA
      MABG (85.1% men; median age, 59 years), and RA-MABG (82.5% men; median age, 61
      years) showed distinctly different patient characteristics. Compared with SABG
      (1.91% OM; 0.73% DSWI), observed OM was lower for BITA-MABG (1.19%, p < 0.001)
      and RA-MABG (1.19%, p < 0.001). DSWI was higher among BITA-MABG (1.08%, p <
      0.001) and similar for RA-MABG (0.71%, p = 0.55). BITA-MABG showed marginally
      increased, likely not clinically significant, OM (AOR, 1.14; 95% CI, 1.00 to
      1.30; p = 0.05) and doubled DSWI (AOR, 2.09; 95% CI, 1.80 to 2.43; p < 0.001). RA
      MABG had similar OM (AOR, 1.01; 95% CI, 0.89 to 1.15; p = 0.85) and DSWI (AOR,
      0.97; 95% CI, 0.83 to 1.13; p = 0.70). Results were consistent across multiple
      subcohorts. A U-shaped OM vs BITA use relation was documented, with worse OM at
      hospitals with low (<5%: AOR, 1.38; 95% CI, 1.18 to 1.61; p < 0.001) and high
      (>=40%: AOR, 1.31; 95% CI, 1.00 to 1.70; p = 0.049) BITA use. CONCLUSIONS: MABG
      in the United States is associated with OM comparable to SABG and increased DSWI
      risk with BITA-MABG. Our findings highlight the importance of surgeon and
      institutional experience and careful patient selection for BITA-MABG. Our short
      term results should not in any way dissuade the use of MABG, given its well
      established long-term survival advantage.

PMID- 29453003
TI  - Effects of AUT00063, a Kv3.1 channel modulator, on noise-induced hyperactivity in
      the dorsal cochlear nucleus.
AB  - The purpose of this study was to test whether a Kv3 potassium channel modulator,
      AUT00063, has therapeutic potential for reversing noise-induced increases in
      spontaneous neural activity, a state that is widely believed to underlie noise
      induced tinnitus. Recordings were conducted in noise exposed and control hamsters
      from dorsal cochlear nucleus (DCN) fusiform cells before and following
      intraperitoneal administration of AUT00063 (30 mg/kg). Fusiform cell spontaneous
      activity was increased in sound-exposed animals, approximating levels that were
      nearly 50% above those of controls. Administration of AUT00063 resulted in a
      powerful suppression of this hyperactivity. The first signs of this suppression
      began 13 min after AUT00063 administration, but activity continued to decline
      gradually until reaching a floor level which was approximately 60% of pre-drug
      baseline by 25 min after drug treatment. A similar suppressive effect of AUT00063
      was observed in control animals, with onset of suppression first apparent at 13
      min post-treatment, but continuing to decline toward a floor level that was 54%
      of pre-drug baseline and was reached 28 min after drug treatment. In contrast, no
      suppression of spontaneous activity was observed in animals given similar
      injections of vehicle (control) solution. The suppressive effect of AUT00063 was
      achieved without significantly altering heart rate and with minimal effects on
      response thresholds, supporting the interpretation that the reductions of
      hyperactivity were not a secondary consequence of a more general physiological
      suppression of the brain or auditory system. These findings suggest that Kv3
      channel modulation may be an effective approach to suppressing spontaneous
      activity in the auditory system and may provide a future avenue for treatment of
      tinnitus resulting from exposure to intense sound.

PMID- 29453004
TI  - Electrochemical surface-enhanced Raman scattering measurement on ligand capped
      PbS quantum dots at gap of Au nanodimer.
AB  - The vibrational characteristics of ligand-capped lead sulfide (PbS) quantum dots
      (QDs) were clarified via electrochemical surface-enhanced Raman spectroscopy (EC
      SERS) using a hybridized system of gold (Au) nanodimers and PbS QDs under
      electrochemical potential control. Enhanced electromagnetic field caused by the
      coupling of QDs with plasmonic Au nanodimers allowed the characteristic behavior
      of the ligand oleic acid (OA) on the PbS QD surface to be detected under
      electrochemical potential control. Binding modes between the QDs and OA molecules
      were characterized using synchronous two-dimensional correlation spectra at
      distinct electrochemical potentials, confirming that the bidentate bridging mode
      was probably the most stable mode even under relatively negative potential
      polarization. Changes in binding modes and molecular orientations resulted in
      fluctuations in EC-SERS spectra. The present observations strongly recommend the
      validity of the QD-plasmonic nanostructure coupled system for sensitive molecular
      detection via EC-SERS.

PMID- 29453005
TI  - Post-mortem quetiapine concentrations in hair segments of psychiatric patients -
      Correlation between hair concentration, dose and concentration in blood.
AB  - Drug analysis in hair is useful when seeking to establish drug intake over a
      period of months to years. Segmental hair analysis can also document whether
      psychiatric patients are receiving a stable intake of antipsychotics. This study
      describes segmental analysis of the antipsychotic drug quetiapine in post-mortem
      hair samples from long-term quetiapine users by ultra-high performance liquid
      chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The aim was to
      obtain more knowledge on quetiapine concentrations in hair and to relate the
      concentration in hair to the administered dose and the post-mortem concentration
      in femoral blood. We analyzed hair samples from 22 deceased quetiapine-treated
      individuals, who were divided into two groups: natural hair colour and
      dyed/bleached hair. Two to six 1cm long segments were analyzed per individual,
      depending on the length of the hair, with 6cm corresponding to the last six
      months before death. The average daily quetiapine dose and average concentration
      in hair for the last six months prior to death were examined for potential
      correlation. Estimated doses ranged from 45 to 1040mg quetiapine daily over the
      period, and the average concentration in hair ranged from 0.18 to 13ng/mg. A
      significant positive correlation was observed between estimated daily dosage of
      quetiapine and average concentration in hair for individuals with natural hair
      colour (p=0.00005), but statistical significance was not reached for individuals
      with dyed/bleached hair (p=0.31). The individual coefficient of variation (CV) of
      the quetiapine concentrations between segments ranged from 3 to 34% for
      individuals with natural hair colour and 22-62% for individuals with
      dyed/bleached hair. Dose-adjusted concentrations in hair were significantly lower
      in females with dyed/bleached hair than in individuals with natural hair colour.
      The quetiapine concentrations in post-mortem femoral blood and in the proximal
      hair segment, segment 1 (S1), representing the last month before death were also
      investigated for correlation. A significant positive correlation was observed
      between quetiapine concentrations in blood at the time of death and
      concentrations in S1 for individuals with natural hair colour (p=0.003) but not
      for individuals with dyed/bleached hair (p=0.31). The blood concentrations of
      quetiapine ranged from 0.006 to 1.9mg/kg, and the quetiapine concentrations in S1
      ranged from 0.22 to 24ng/mg. The results of this study suggest a positive
      correlation of quetiapine between both concentrations in hair and doses, and
      between proximal hair (S1) and blood concentrations, when conditions such as hair
      treatments are taken into consideration.

PMID- 29453006
TI  - Illicit and prescription drug misuse as reported to the Maine Diversion Alert
      Program.
AB  - BACKGROUND: The opioid epidemic is rapidly evolving and new tools are needed to
      combat drug abuse. The Maine Diversion Alert Program (DAP) is an informational
      resource that facilitates communication about drug arrests between the criminal
      justice and healthcare fields. The objectives of this report were to: (1)
      describe the illegal and prescription pharmaceuticals reported to the DAP; (2)
      determine if the drugs implicated in arrests changed from the first to latter
      half of 2016; (3) identify the demographic and other characteristics of
      arrestees; and (4) outline the strengths and limitations of the DAP for other
      areas considering implementing similar programs. METHODS: The arrests (N=2,368,
      31.4% female, mean age=33.7, SD=9.9, Min=18, Max=71.5) reported to the DAP were
      examined. Drugs were classified by Drug Enforcement Administration Schedule (I-V,
      non-controlled prescription) and into families (opioids, stimulants, sedatives,
      hallucinogens, and other). A comparison between the first and second half of 2016
      and arrest by county was completed. RESULTS: Arrests involved 2,957 substances
      (drugs and paraphernalia). Most arrests (80.6%) involved a single drug. One-third
      (33.2%) of arrests involved illicit drugs (i.e. Schedule I) and three-fifths
      (59.8%) were for controlled prescription medical drugs (i.e. Schedule II-V), and
      a minority (6.8%) involved non-controlled prescription drugs (e.g. gabapentin,
      bupropion). Opioids (e.g. heroin, buprenorphine, and oxycodone) accounted for
      over-half (51.3%) of arrests followed by stimulants (29.0%, e.g. cocaine), and
      sedatives (7.6%). Arrests for oxycodone significantly decreased (51.9%) and
      alprazolam increased (89.3%) during 2016. Arrestees for non-controlled
      prescription drugs were older than arrestees for illegal drugs. Arrests,
      correcting for population, were most common in more urban (e.g. Androscoggin and
      Cumberland) counties. CONCLUSIONS: Opioids (illicit and prescription) account for
      over half of all arrests. However, arrests for oxycodone decreased while arrests
      for benzodiazepines, and especially alprazolam, increased in 2016. The DAP is a
      novel source of information for healthcare decisions and can empirically inform
      law enforcement about drug misuse and addiction.

PMID- 29453007
TI  - When is myocarditis indeed the cause of death?
AB  - Attribution of death to myocarditis continues to be a controversial issue in
      forensic pathology, despite the existence of established histopathological
      criteria as well as complementary investigations. The aim of the study was two
      fold: (a) to retrospectively analyse the data obtained from a series of clinical
      and forensic autopsies in order to assess the number of cases with death
      attributed to myocarditis, and (b) to reevaluate these cases in order to assess
      how properly the histopathological diagnosis of myocarditis conformed to
      established criteria and therefore how accurately these were used on the basis of
      all postmortem investigation findings to conclude the cause of death. 2474
      clinical and forensic autopsies were taken into consideration. Myocarditis was
      recorded as the official, underlying cause of death in 48 cases. Of those, 8
      cases were considered to accurately conform to the histopathological Dallas
      criteria for the presence of myocarditis and could therefore be classified as
      cases of fatal myocarditis. In 19 out of 48 cases, description of focal
      myocarditis was considered to accurately fulfill the histopathological Dallas
      criteria for the presence of myocarditis. However, data provided by histological
      analysis and virology testing result reevaluation allowed alternative causes of
      death to be speculated. In another 21 out of 48 cases, description of focal
      myocardial inflammation was considered to inaccurately meet the histopathological
      Dallas criteria for the presence of myocarditis. The findings of our own study
      appear to be in agreement with previous observations in similar study groups and
      highlight that since myocarditis may occur in association with many diseases, a
      great deal of evidence is required before settling on categorical conclusions.

PMID- 29453008
TI  - Forensic image analysis - CCTV distortion and artefacts.
AB  - As a result of the worldwide deployment of surveillance cameras, authorities have
      gained a powerful tool that captures footage of activities of people in public
      areas. Surveillance cameras allow continuous monitoring of the area and allow
      footage to be obtained for later use, if a criminal or other act of interest
      occurs. Following this, a forensic practitioner, or expert witness can be
      required to analyse the footage of the Person of Interest. The examination
      ultimately aims at evaluating the strength of evidence at source and activity
      levels. In this paper, both source and activity levels are inferred from the
      trace, obtained in the form of CCTV footage. The source level alludes to features
      observed within the anatomy and gait of an individual, whilst the activity level
      relates to activity undertaken by the individual within the footage. The strength
      of evidence depends on the value of the information recorded, where the activity
      level is robust, yet source level requires further development. It is therefore
      suggested that the camera and the associated distortions should be assessed first
      and foremost and, where possible, quantified, to determine the level of each type
      of distortion present within the footage. A review of the 'forensic image
      analysis' review is presented here. It will outline the image distortion types
      and detail the limitations of differing surveillance camera systems. The aim is
      to highlight various types of distortion present particularly from surveillance
      footage, as well as address gaps in current literature in relation to assessment
      of CCTV distortions in tandem with gait analysis. Future work will consider the
      anatomical assessment from surveillance footage.

PMID- 29453009
TI  - Advances in concrete materials for sewer systems affected by microbial induced
      concrete corrosion: A review.
AB  - Microbial induced concrete corrosion (MICC) is recognized as one of the main
      degradation mechanisms of subsurface infrastructure worldwide, raising the demand
      for sustainable construction materials in corrosive environments. This review
      aims to summarize the key research progress acquired during the last decade
      regarding the understanding of MICC reaction mechanisms and the development of
      durable materials from an interdisciplinary perspective. Special focus was laid
      on aspects governing concrete - micoorganisms interaction since being the central
      process steering biogenic acid corrosion. The insufficient knowledge regarding
      the latter is proposed as a central reason for insufficient progress in tailored
      material development for aggressive wastewater systems. To date no cement-based
      material exists, suitable to withstand the aggressive conditions related to MICC
      over its entire service life. Research is in particular needed on the impact of
      physiochemical material parameters on microbial community structure, growth
      characteristics and limitations within individual concrete speciation. Herein an
      interdisciplinary approach is presented by combining results from material
      sciences, microbiology, mineralogy and hydrochemistry to stimulate the
      development of novel and sustainable materials and mitigation strategies for
      MICC. For instance, the application of antibacteriostatic agents is introduced as
      an effective instrument to limit microbial growth on concrete surfaces in
      aggressive sewer environments. Additionally, geopolymer concretes are introduced
      as highly resistent in acid environments, thus representing a possible green
      alternative to conventional cement-based construction materials.

PMID- 29453010
TI  - Qzone use and depression among Chinese adolescents: A moderated mediation model.
AB  - BACKGROUND: Social networking sites (SNSs), which provide abundant social
      comparison opportunities, are ubiquitous around the world, especially among
      adolescents. In China, Qzone stands out as the most popular SNS. Due to the
      opportunity it provides for meticulous self-presentation, SNS may give the
      impression that others are doing better, which is detrimental to individuals'
      well-being. Based on social comparison theory, the current study aimed to
      investigate the association between Chinese adolescents' SNS (Qzone) use and
      depression, as well as the mediating role of negative social comparison and the
      moderating role of self-esteem. METHOD: A total of 764 adolescents (aged 12-18
      years, M = 14.23, SD = 1.75), who had an active Qzone account, were recruited
      voluntarily to complete questionnaires on Qzone use intensity, negative social
      comparison on Qzone, self-esteem, and depression. RESULTS: More intense Qzone use
      was associated with higher level of negative social comparison on Qzone, which
      fully mediated the association between Qzone use and depression. Moreover, the
      mediating effect of negative social comparison on Qzone was moderated by self
      esteem. The specific link between Qzone use and negative social comparison was
      weaker among adolescents with high self-esteem than those with low self-esteem.
      LIMITATIONS: As all the data in this study were self-reported and cross
      sectional, causal associations cannot be identified. Additionally, the specific
      activities on SNS were not identified. CONCLUSIONS: Negative social comparison
      may be a key factor and mechanism accounting for the positive association between
      SNS use and depression, while self-esteem could protect adolescents from the
      adverse outcome of SNS use.

PMID- 29453011
TI  - Emotional availability in mothers with borderline personality disorder and
      mothers with remitted major depression is differently associated with
      psychopathology among school-aged children.
AB  - BACKGROUND: Both, maternal borderline personality disorder (BPD) and maternal
      major depressive disorder (MDD) are often associated with adverse consequences
      for children, including increased risk for child behavior problems. Reduced
      maternal emotional availability might play a critical role in transmitting
      maternal psychopathology on the child. Our aim was to investigate the association
      between emotional availability and maternal BPD and MDD in remission (rMDD), and
      if this interrelatedness mediates the association between maternal mental
      disorders and child behavior problems. METHODS: The interaction of 178 mother
      child dyads was assessed during a play situation using the Emotional Availability
      Scales. Children were between 5 and 12 years old. Regression analyses were used
      to investigate the impact of maternal BPD and maternal rMDD on emotional
      availability. Ordinary least squares regression analyses using bootstrapping were
      conducted to investigate the mediating effect of emotional availability on the
      association between maternal mental disorders and child behavior problems.
      RESULTS: Mothers with BPD showed increased hostility during mother-child
      interaction, whereas history of MDD was associated with reduced sensitivity.
      Maternal hostility was a mediator between maternal BPD and number of child
      psychiatric disorders, as well as externalizing and internalizing behavior.
      Maternal sensitivity mediated the association between maternal rMDD and number of
      child psychiatric disorders, as well as internalizing child behavior.
      CONCLUSIONS: Our data suggest that mothers with BPD show a qualitatively
      different pattern of emotional availability compared to mothers with rMDD. These
      patterns might reflect two separate pathways of transgenerational transmission of
      aspects of maternal mental disorders, where intervention and training programs
      could start: maternal rMDD impacts on child behavior problems via reduced
      sensitivity, and maternal BPD via increased hostility, which could both be
      addressed with specific therapeutic interventions.

PMID- 29453012
TI  - Membrane bioreactor performance in treating Algiers' landfill leachate from using
      indigenous bacteria and inoculating with activated sludge.
AB  - This study focuses on the treatment of both organic and metallic pollution in the
      Staoueli landfill leachate. This leachate contains a large amount of organic and
      inorganic matter and it must imperatively be treated before being released into
      the environment. Our work presents a comparative study between two membrane
      sequenced batch bioreactors (B2 contains indigenous leachate bacteria and B1
      contains activated sludge). The purpose is to assess the best treatment to use,
      one that allows the reduction of the polluting load of the leachate and a
      reduction of membrane fouling. Performances were evaluated by measuring the
      chemical oxygen demand (COD) and the metal content of the leachate (zinc, iron).
      The results showed a similar COD removal efficiency in B2 (95%) and B1 (93%).
      Coupling the bioreactors with an ultrafiltration process allowed a notable
      reduction in zinc and iron concentrations: Fe of 35% and Zn of 78% for B1UF, and
      Fe of 71% and Zn of 74% for B2UF.

PMID- 29453013
TI  - AERMOD as a Gaussian dispersion model for planning tracer gas dispersion tests
      for landfill methane emission quantification.
AB  - The measurement of methane emissions from landfills is important to the
      understanding of landfills' contribution to greenhouse gas emissions. The Tracer
      Dispersion Method (TDM) is becoming widely accepted as a technique, which allows
      landfill emissions to be quantified accurately provided that measurements are
      taken where the plumes of a released tracer-gas and landfill-gas are well-mixed.
      However, the distance at which full mixing of the gases occurs is generally
      unknown prior to any experimental campaign. To overcome this problem the present
      paper demonstrates that, for any specific TDM application, a simple Gaussian
      dispersion model (AERMOD) can be run beforehand to help determine the distance
      from the source at which full mixing conditions occur, and the likely associated
      measurement errors. An AERMOD model was created to simulate a series of TDM
      trials carried out at a UK landfill, and was benchmarked against the experimental
      data obtained. The model was used to investigate the impact of different factors
      (e.g. tracer cylinder placements, wind directions, atmospheric stability
      parameters) on TDM results to identify appropriate experimental set ups for
      different conditions. The contribution of incomplete vertical mixing of tracer
      and landfill gas on TDM measurement error was explored using the model. It was
      observed that full mixing conditions at ground level do not imply full mixing
      over the entire plume height. However, when full mixing conditions were satisfied
      at ground level, then the error introduced by variations in mixing higher up were
      always less than 10%.

PMID- 29453014
TI  - Predictors of illegal dumping at charitable collection points.
AB  - Cleaning and disposal of illegal dumping at charitable collection points costs
      charities and diverts funds from their charitable programs. However, there is no
      published literature that attempts to better understand this problem. The current
      study assesses site-specific characteristics, community level indicators and
      sociodemographic factors as predictors of both charity stores and collection bin
      dumping in the metropolitan area of Perth, Australia. Multiple regression
      analyses revealed that higher levels of dumping at stores were predicted by being
      open on Sundays, the presence of gates/fencing, bringing bins in at night,
      greater 5-year mobility and lower levels of education and occupation in the area.
      The analysis also suggests that preventative measures have not necessarily been
      effective at reducing the amount of illegal dumping at stores. For charity bins,
      significant predictors of higher levels of dumping included private land
      ownership, if the site is shared with bins from another charity, the number of
      bins at the site, the number of days serviced per week, if the bin/s are located
      at a park/reserve and greater 5-year mobility. These results indicate that there
      is a combination of site-specific characteristics and community level indicators
      that play a role in illegal dumping at charitable collection points and indicate
      the type of interventions which may be successful in reducing illegal dumping.
      These may include improved maintenance, better placement of bins and signage and
      collaborations with real estate agents.

PMID- 29453015
TI  - Metabolomic profiling of Campylobacter jejuni with resistance gene ermB by ultra
      high performance liquid chromatography-quadrupole time-of-flight mass
      spectrometry and tandem quadrupole mass spectrometry.
AB  - The metabolome changes of Campylobacter jejuni with resistant gene ermB remain
      unclear. Here, we described an untargeted metabolomic workflow based on ultra
      high performance liquid chromatography-quadrupole time-of-flight mass
      spectrometry to investigate the metabolites perturbations mediated by ermB in C.
      jejuni. After optimization of extractants and chromatographic conditions, the
      combination of 100% methanol extraction with a 12 min gradient by C18 column was
      adopted for untargeted metabolomic profiling in reversed phase separation.
      Meanwhile, 60% methanol extraction followed by a 14 min separation using
      hydrophilic interaction chromatography column was suitable to complementally
      expand the metabolite coverage of C. jejuni. Multivariate statistical analysis
      was performed by means of orthogonal projection to latent structures-discriminant
      analysis to select metabolic features. The selected features were further
      confirmed by ultra-high performance liquid chromatography-tandem quadrupole mass
      spectrometry. A total of thirty-six differential metabolites between the
      susceptible strain (C. jejuni NCTC 11168) and resistant stain (C. jejuni NCTC
      11168 with ermB) were identified. These pivotal metabolites were primarily
      participated in biological processes as cell signaling, membrane
      integrity/stability, fuel and energy source/storage and nutrient. The biofilm
      formation capability of resistant strain was inferior to that of susceptible
      strain, confirming the influence of ermB on membrane integrity/stability of C.
      jejuni. Our findings revealed important metabolic regulatory pathways associated
      with resistant C. jejuni with ermB.

PMID- 29453016
TI  - Metabolic profiling of Gegenqinlian decoction in rat plasma, urine, bile and
      feces after oral administration by ultra high performance liquid chromatography
      coupled with Fourier transform ion cyclotron resonance mass spectrometry.
AB  - Gegenqinlian decoction (GQLD) as a traditional Chinese medical (TCM) prescription
      is made from four Chinese herbs and has been used for centuries to treat pyrexia
      and diarrhea. In this work, an ultra-high performance liquid chromatography
      coupled with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC
      FT-ICR-MS) method was established to profile the metabolic fate of GQLD in rat
      plasma, urine, bile and feces. The analysis was performed on a Waters Acquity
      UPLC HSS T3 column (2.1 mm * 100 mm, 1.8 MUm) at 35  degrees C within 25 min. A
      total of 174 compounds mainly including flavonoids, alkaloids and triterpenoids
      in rat plasma, urine, bile and feces after oral administration of GQLD were
      identified or tentatively characterized by comparison with retention times,
      accurate mass within 5 ppm error and their characteristic MS fragmentation ions.
      Among compounds in rats, 107 compounds are prototypes and 67 compounds are
      metabolites. Results demonstrated that metabolic pathways of GQLD in rats
      included methylation, demethylation, hydrogenation, hydrolysis, hydroxylation,
      methoxylation, sulfate conjugation and glucuronide conjugation. A clear
      understanding of the absorption and metabolism of GQLD is very important in its
      rational clinical use and pharmacological research. These findings enhance our
      understanding of the metabolism and effective forms of GQLD.

PMID- 29453017
TI  - [Retinal arterial macroaneurysm and hypertension: Importance of the
      multidisciplinary approach].

PMID- 29453018
TI  - [Management of Rhinosinusitis in Primary Care].
AB  - Acute rhinosinusitis is an important health problem. Even though its frequency is
      not well documented in our country?, the economic burden it bears is not
      insignificant as it notably alters the quality of life of affected patients. Its
      diagnosis is generally clinical in nature, with further studies reserved only for
      the differential diagnoses of complications or tumour-like processes. The most
      frequent causes are viral infections, although Streptococcus pneumoniae and
      Haemophilus influenzae are the most commonly isolated bacterial agents. Although
      complications are uncommon nowadays, they can be serious when they occur, and
      commonly include orbital infections, closely followed in frequency by
      intracranial and bone infections. Treatment should consist of symptomatic
      measures, like saline rinses and antibiotics in cases of bacterial origin.

PMID- 29453019
TI  - [Electrocardiographic changes due to a giant para-oesophageal hernia].

PMID- 29453020
TI  - 2018 consensus of the Taiwan Society of Cardiology and the Diabetes Association
      of Republic of China (Taiwan) on the pharmacological management of patients with
      type 2 diabetes and cardiovascular diseases.
AB  - The global incidence and prevalence of type 2 diabetes have been escalating in
      recent decades. Patients with type 2 diabetes have an increased risk of
      atherosclerotic cardiovascular disease (ASCVD). About two-thirds of death in type
      2 diabetes are due to ASCVD, including 40% from coronary heart disease (CHD), 15%
      from heart failure (HF), and 10% from stroke. The association between
      hyperglycemia and elevated CV risk has been demonstrated in multiple cohort
      studies. However, clinical trials of intensive glucose reduction did not
      significantly reduce macrovascular outcomes. It remains unclear whether the
      absence of demonstrable benefits is attributed to the inclusion of patients with
      far advanced ASCVD in whom a short treatment period is barely enough for CV
      protective effects to be shown, or complications associated with the treatment
      such as hypoglycemia hamper the beneficial effects to manifest, or simply glucose
      lowering per se is ineffective. Since the US FDA issued a mandate in December
      2008 that every new anti-diabetic agent requires rigorous assessments of its CV
      safety, there have been more than 200,000 patients enrolled in a number of
      randomized controlled trials (RCTs), and around half of them have been completed
      and published. The results of these CV outcome trials are important for
      clinicians in their clinical practice, and also provide an opportunity for
      academic society to formulate treatment guidelines or consensus to provide
      specific recommendations for glucose control in various CV diseases. The Taiwan
      Society of Cardiology (TSOC) and the Diabetes Association of Republic of China
      (DAROC), aiming to formulate a treatment consensus in type 2 diabetic patients
      with CVD, have appointed a jointed consensus group for the 2018 Consensus of
      TSOC/DAROC (Taiwan) on the Pharmacological Management of Patients with Type 2
      Diabetes and CV Diseases. The consensus is comprised of 5 major parts: 1)
      Treatment of diabetes in patients with hypertension, 2) Treatment of diabetes in
      patients with CHD, 3) Treatment of diabetes in patients with stage 3 chronic
      kidney disease, 4) Treatment of diabetes in patients with a history of stroke,
      and 5) Treatment of diabetes in patients with HF. The members of the consensus
      group comprehensively reviewed all the evidence, mainly RCTs, and also included
      meta-analyses, cohort studies, and studies using claim data. The treatment
      targets of HbA1c were provided. The anti-diabetic agents were ranked according to
      their clinical evidence. The consensus is not mandatory. The final decision may
      need to be individualized and based on clinicians' discretion.

PMID- 29453021
TI  - Towards sustainable feedstocks: A guide to electron donors for microbial carbon
      fixation.
AB  - The replacement of fossil and agricultural feedstocks with sustainable
      alternatives for the production of chemicals and fuels is a societal and
      environmental necessity. This challenge can be tackled by using inorganic or one
      carbon compounds as electron donors for microbial CO2 fixation and bioproduction.
      Yet, considering the wide array of microbial electron donors, which are the best
      suited for bioindustry? Here, we propose criteria to evaluate these compounds,
      considering factors such as production methods, physicochemical properties, and
      microbial utilization. H2, CO, and formate emerge as the most promising electron
      donors as they can be produced electrochemically at high efficiency and,
      importantly, have reduction potentials low enough to directly reduce the cellular
      electron carriers. Still, further research towards the production and utilization
      of other electron donors-especially phosphite-might unlock the full potential of
      microbial CO2 fixation and bioproduction.

PMID- 29453022
TI  - Exploring factors that influence students' attitudes toward midwifery in Jordan:
      Measuring psychometric properties of a newly developed tool.
AB  - Students' professional choice to proceed in midwifery is influenced by many
      factors. This study validated an instrument developed to assess students'
      attitudes toward midwifery in Jordan. It also addressed the motivating and de
      motivating factors influencing students' decision concerning joining and
      continuing in midwifery. A descriptive, cross-section study was conducted on a
      convenience sample of 374 midwifery students representing private, governmental,
      and military midwifery colleges. The researchers developed the study
      questionnaire through conducting a comprehensive literature review, organizing
      common themes and consulting experts. Exploratory factor analysis and tests of
      normality and reliability, including Cronbach's Alpha and Bartlett's test, were
      used in the analysis. The result was three factors were explained by 23 items.
      They were as follows: professional knowledge, professional motivation factors,
      and de-motivating professional factors. The first 8 items explained nearly 61% of
      the variance. Cronbach's Alpha was 0.834 with a range of 0.835-0.839. The
      Spearman-Brown coefficient was 0.81 and Guttman Split-Half coefficient was 0.83.
      Issues of reliability and validity require a repetitive process of testing under
      a range of circumstances to ensure both stability and representation of the
      construct. However, addressing factors found to have impact of students'
      decisions is crucial to improve retention of high quality students.

PMID- 29453023
TI  - Implications of altered maternal cytokine concentrations on infant outcomes in
      children with prenatal alcohol exposure.
AB  - Excessive alcohol consumption has been shown to increase serum plasma levels of
      numerous immune cytokines. Maternal immune activation and elevated cytokines have
      been implicated in certain neurological disorders (e.g., autism and
      schizophrenia) in the offspring. We investigated the hypothesis that elevated
      cytokines during pregnancy are a risk factor in women who gave birth to a child
      with Fetal Alcohol Spectrum Disorder (FASD) or a child with neurobehavioral
      impairment, regardless of prenatal alcohol exposure. Moderate to heavy alcohol
      exposed (AE) (N = 149) and low or no alcohol-exposed (LNA) (N = 92) women were
      recruited into the study during mid pregnancy (mean of 19.8 +/- 5.8 weeks'
      gestation) in two regions of Ukraine: Khmelnytsky and Rivne. Maternal blood
      samples were obtained at enrollment into the study at early to mid-pregnancy and
      during a third-trimester follow-up visit and analyzed for plasma cytokines.
      Children were examined at 6 and/or 12 months of age and were classified as having
      FASD if their mothers reported alcohol use and if they had at least one
      standardized score (Bayley Scales of Infant Development II Mental Development
      Index [MDI], or Psychomotor Development Index [PDI]) below 85 with the presence
      or absence of physical features of FASD. In multivariate analyses of maternal
      cytokine levels in relation to infant MDI and PDI scores in the entire sample,
      increases in the ratio of TNF-alpha/IL-10 and IL-6/IL-10 were negatively
      associated with PDI scores at 6 months (p = 0.020 and p = 0.036, respectively)
      and 12 months (p = 0.043 and p = 0.029, respectively), and with MDI scores at 12
      months (p = 0.013 and p = 0.050, respectively). A reduction in the odds ratio of
      having an FASD child was observed with increasing levels of IL-1beta, IL-2, IL-4,
      IL-6, and IL-10 in early to mid-pregnancy and IL-1beta and IL-10 during late
      pregnancy. However, women that failed to increase IL-10 levels in the third
      trimester in order to maintain the balance of pro- and anti-inflammatory
      cytokines had an elevated risk of having an FASD child, specifically a
      significant increase in the odds ratio of FASD with every one-unit log increase
      in late pregnancy TNF-alpha/IL-10 levels (aOR: 1.654, CI: 1.096-2.495, p =
      0.017). These data support the concept that disruptions in the balance between
      pro- and anti-inflammatory cytokines may contribute to neurobehavioral impairment
      and alter the risk of FASD.

PMID- 29453024
TI  - Simultaneous determination of ibuprofen and its metabolites in complex equine
      urine matrices by GC-EI-MS in excretion study in view of doping control.
AB  - A novel assay for the simultaneous determination of ibuprofen (IBU) and its four
      probable metabolites, 1-hydroxyibuprofen (1-OH IBU), 2-hydroxyibuprofen (2-OH
      IBU), 3-hydroxyibuprofen (3-OH IBU) and carboxyibuprofen (CBX IBU) in equine
      urine samples with the application of Gas Chromatography-Electron Ionization-Mass
      Spectrometry (GC-EI-MS) has been developed and elaborated. The new approach for
      sample preparation including minimizing matrix effects by the application of weak
      cation exchange solid-phase extraction together with strong cation exchange solid
      phase extraction has been applied. The GC-EI-MS method was validated to
      demonstrate specificity, matrix effect, linearity, limit of detection (LOD) and
      quantification (LOQ), precision, trueness, carry-over and stability by using the
      matrix-matched quality control samples. Additionally, extraction yield was
      evaluated. The assay achieved the LOQ of 1.75 MUg mL-1, 0.62 MUg mL-1, 4.15 MUg
      mL-1, 0.58 MUg mL-1 and 4.04 MUg mL-1 for IBU, 1-OH IBU, 2-OH IBU, 3-OH IBU and
      CBX IBU, respectively. The developed method has been successfully applied to the
      excretion study in horses, in which a single oral IBU dose was administered to
      twelve horses (mares and geldings) and equine urine samples were collected for 5
      or 6 days after the drug administration. Data on the detection and determination
      of three IBU metabolites, 2-OH IBU, 3-OH IBU and CBX IBU in equine urine samples
      has been presented for the first time. The obtained results indicated the rapid
      excretion of IBU and its metabolites that were detectable only in the first day
      after the drug administration. IBU was mainly the most abundant compound detected
      in equine urine samples (with two exceptions in the case of samples collected
      from two horses, for which the highest instrumental responses were obtained for
      CBX IBU). The received results have indicated that two major IBU metabolites, CBX
      IBU and 2-OH IBU can be important markers for the IBU abuse in view of doping
      control in equestrian sports.

PMID- 29453026
TI  - Assessment of titanium metallization thin film deposited on alumina substrate:
      Microstructure and nano-indentation.
AB  - Surface titanium (Ti) metallization was conducted on alumina (Al2O3) through
      chemical vapor deposition (CVD) method derived from non-contact pack cementation.
      The effects of different deposition temperature (1000  degrees C, 1050  degrees
      C, and 1100  degrees C) were examined in this scenario. The morphology, phase
      composition, and interfacial defects of the resulting films were systematically
      investigated through scanning electron microscopy, energy dispersive
      spectrometry, and X-ray diffraction. The nanomechanical characterization of the
      proposed thin films was evaluated by conducting nano-indentation tests at
      different depths. The results revealed that uniform Ti films were coated on the
      Al2O3 substrate. During coating, the atoms on the matrix surface were driven to
      form different structure due to different deposition temperature, leading to
      disparate morphologies of the surface and the interface, which consequently
      influenced the binding force between the film and the substrate. Moreover, the
      nanomechanical properties were found to be related to the internal and interface
      structure. Decreased modulus and hardness were obtained for metallization films
      treated at 1050  degrees C, and plastic deformation was the main deformation
      pattern.

PMID- 29453025
TI  - Material properties of the brain in injury-relevant conditions - Experiments and
      computational modeling.
AB  - Material properties of the brain have been extensively studied but remain poorly
      characterized. The vast variations in constitutive models and material constants
      are well documented. However, no study exists to translate the variations into
      disparities in impact-induced brain strains most relevant to brain injury. Here,
      we reviewed a subset of injury-relevant brain material properties either
      characterized in experiments or adopted in recent head injury models. To
      highlight how variations in measured brain material properties manifested in
      simulated brain strains, we selected six experiments that have provided a
      complete set of brain material model and constants to implement a common head
      injury model. Responses resulting from two extreme events representing a high
      rate cadaveric head impact and a low-rate in vivo head rotation, respectively,
      varied substantially. We hypothesized, and further confirmed, that the time
      varying shear moduli at the appropriate time scales (e.g., ~5 ms and ~40 ms
      corresponding to the impulse durations of the major acceleration peaks for the
      two impacts, respectively), rather than the initial or long-term shear moduli,
      were the most indicative of impact-induced brain strains. These results
      underscored the need to implement measured brain material properties into an
      actual head injury model for evaluation. They may also provide guidelines to
      better characterize brain material properties in future experiments and head
      injury models. Finally, our finding provided a practical solution to satisfy head
      injury model validation requirements at both ends of the impact severity
      spectrum. This would improve the confidence in model simulation performance
      across a range of time scales relevant to concussion and sub-concussion in the
      real-world.

PMID- 29453027
TI  - Effects of microstructure transformation on mechanical properties, corrosion
      behaviors of Mg-Zn-Mn-Ca alloys in simulated body fluid.
AB  - Magnesium and its alloys have unique advantages to act as resorbable bone
      fixation materials, due to their moderate mechanical properties and
      biocompatibility, which are similar to those of human tissue. However, early
      resorption and insufficient mechanical strength are the main problems that hinder
      their application. Herein, the effects of microstructure transformation on the
      mechanical properties and corrosion performance of Mg-Zn-Mn-Ca were investigated
      with electrochemical and immersion measurements at 37  degrees C in a simulated
      body fluid (SBF). The results showed that the number density of Ca2Mg6Zn3/Mg2Ca
      precipitates was remarkably reduced and grain sizes were gradually increased as
      the temperature increased. The alloy that received the 420  degrees C/24 h
      treatment demonstrated the best mechanical properties and lowest corrosion rate
      (5.94 mm/a) as well as presented a compact and denser film than the others. The
      improvement in mechanical properties could be explained by the eutectic compounds
      and phases (Mg2Ca/Ca2Mg6Zn3) gradually dissolving into a matrix, which caused
      severely lattice distortion and facilitated structural re-arrangement of the
      increased Ca solute. Moreover, the difference in potential between the
      precipitates and the matrix is the main essence for micro-galvanic corrosion
      formation as well as accelerated the dissolution activity and current exchange
      density at the Mg/electrolyte interface. As a result, the best Mg alloys
      corrosion resistance must be matched with a moderate grain size and phase volume
      fractions.

PMID- 29453028
TI  - Transposons: a blessing curse.
AB  - The genomes of most plant species are dominated by transposable elements (TEs).
      Once considered as 'junk DNA', TEs are now known to have a major role in driving
      genome evolution. Over the last decade, it has become apparent that some stress
      conditions and other environmental stimuli can drive bursts of activity of
      certain TE families and consequently new TE insertions. These can give rise to
      altered gene expression patterns and phenotypes, with new TE insertions sometimes
      causing flanking genes to become transcriptionally responsive to the same stress
      conditions that activated the TE in the first place. Such connections between TE
      mediated increases in diversity and an accelerated rate of genome evolution
      provide powerful mechanisms for plants to adapt more rapidly to new environmental
      conditions. This review will focus on environmentally induced transposition, the
      mechanisms by which it alters gene expression, and the consequences for plant
      genome evolution and breeding.

PMID- 29453029
TI  - Systems biology of the human microbiome.
AB  - Recent research has shown that the microbiome-a collection of microorganisms,
      including bacteria, fungi, and viruses, living on and in a host-are of
      extraordinary importance in human health, even from conception and development in
      the uterus. Therefore, to further our ability to diagnose disease, to predict
      treatment outcomes, and to identify novel therapeutics, it is essential to
      include microbiome and microbial metabolic biomarkers in Systems Biology
      investigations. In clinical studies or, more precisely, Systems Medicine
      approaches, we can use the diversity and individual characteristics of the
      personal microbiome to enhance our resolution for patient stratification. In this
      review, we explore several Systems Medicine approaches, including Microbiome Wide
      Association Studies to understand the role of the human microbiome in health and
      disease, with a focus on 'preventive medicine' or P4 (i.e., personalized,
      predictive, preventive, participatory) medicine.

PMID- 29453030
TI  - Effects of triphenyltin on glycinergic transmission on rat spinal neurons.
AB  - Glycine is a fast inhibitory transmitter like gamma-aminobutyric acid in the
      mammalian spinal cord and brainstem, and it is involved in motor reflex,
      nociception, and neuronal development. Triphenyltin (TPT) is an organometallic
      compound causing environmental hazard to many wild creatures. Our previous
      findings show that TPT ultimately induces a drain and/or exhaustion of glutamate
      in excitatory presynaptic nerve terminals, resulted in blockage of
      neurotransmission as well as methylmercury. Therefore, we have investigated the
      neurotoxic mechanism how TPT modulates inhibitory glycinergic transmission in the
      synaptic bouton preparation of rat isolated spinal neurons using a patch clamp
      technique. TPT at environmentally relevant concentrations (3-300 nM)
      significantly increased the number of frequency of glycinergic spontaneous and
      miniature inhibitory postsynaptic currents (sIPSC and mIPSC) without affecting
      the current amplitude and decay time. The TPT effects were also observed in
      external Ca2+-free solution containing tetrodotoxin (TTX) but removed in Ca2+
      free solution with both TTX and BAPTA-AM (Ca2+ chelator). On the other hand, the
      amplitude of glycinergic evoked inhibitory postsynaptic currents (eIPSCs)
      increased with decreasing failure rate (Rf) and paired pulse ratio (PPR) in the
      presence of 300 nM TPT. At a high concentration (1 uM), TPT completely blocked
      eIPSCs after a transient facilitation. Overall, these results suggest that TPT
      directly acts transmitter-releasing machinery in glycinergic nerve terminals.
      Effects of TPT on the nerve terminals releasing fast transmitters were greater in
      the order of glycinergic > glutamatergic > GABAergic ones. Thus, TPT is supposed
      to cause a strong synaptic modulations on glycinergic neurotransmission in wild
      creatures.

PMID- 29453031
TI  - Spaces of hope? Youth perspectives on health and wellness in indigenous
      communities.
AB  - This article addresses an apparent paradox between academic and policy depictions
      of American Indian reservations as "broken" and "unhealthy" places, and
      Indigenous youth perceptions of reservations as spaces of "health" and
      "wellness." Public health literature often frames reservations as damaged, health
      denying places, chronicling the extraordinarily high rates of suicide, substance
      abuse, as well as vast health disparities. Despite these dire statistics, our
      research with Native youth in San Diego County found that young people chose to
      primarily emphasize their positive experiences with, and attachments to, their
      reservations. In this article, we share strength- and desire-based narratives to
      explore how reservations can serve as spaces of wellness for Indigenous youth,
      despite ongoing settler colonial harm. We seek to expand the discussion on the
      unintended consequences of deficit-centered scholarship by arguing that health
      research should also engage with the narratives of hope and desire that are
      reflective of the way many Native youth feel about their communities. In this
      article, we urge scholars and practitioners to rethink how we conduct health
      research to include methodologies that listen to the narratives and experiences
      of those who, day in and day out, navigate settler colonial landscapes, while
      continuing to create spaces of hope and healing.

PMID- 29453032
TI  - Impact of metformin on gastric adenocarcinoma survival: A Belgian population
      based study.
AB  - BACKGROUND: Preclinical studies have shown anticancer activities of metformin in
      gastric cancer and a recent epidemiological study showed a decrease in recurrence
      and mortality of gastric cancer in metformin users. This study aimed to assess
      the impact of metformin on gastric cancer survival in diabetic patients at a
      Belgian population level. METHODS: We conducted an observational, population
      based study by linking data of the Belgian Cancer Registry with medical claims
      data coming from the health insurance companies for patients diagnosed with stage
      I to III gastric adenocarcinoma between 2006 and 2012. Information on gastric
      cancer-specific deaths was retrieved from mortality records collected by regional
      governments. Time-dependent Cox regression models were used to calculate hazard
      ratios (HRs) and 95% confidence intervals (CI) for overall survival (OS) and
      cancer-specific mortality (CSS). RESULTS: In our population of 371 patients, a
      reduction in all-cause mortality was observed in metformin users (adjusted HR =
      0.73, 95% CI: [0.52; 1.01], p = 0.06) but not for cancer specific mortality
      (adjusted HR = 0.86, 95% CI: [0.56; 1.33], p = 0.50). Pre-diagnosis exposure to
      metformin was associated with a significant improvement in OS (adjusted HR =
      0.75, 95% CI: [0.57; 0.98], p = 0.04) that was not significant for CSS (adjusted
      HR = 0.89, 95% CI: [0.62; 1.28], p = 0.52). Moreover, no dose-response
      relationship between metformin use and either all-cause or cancer-specific
      mortality was observed. CONCLUSION: In the first population based study of
      metformin use in gastric cancer adenocarcinoma patients with previous diabetes,
      our findings suggest that metformin use might improve overall mortality. However,
      no such association was found for cancer-specific survival. Additional studies in
      other populations are required.

PMID- 29453033
TI  - The Social Attribution Task - Multiple Choice (SAT-MC): Psychometric comparison
      with social cognitive measures for schizophrenia research.
AB  - The Social Attribution Task-Multiple Choice (SAT-MC) tests the ability to extract
      social themes from viewed object motion. This form of animacy perception is
      thought to aid the development of social inference, but appears impaired in
      schizophrenia. The current study was undertaken to examine psychometric
      equivalence of two forms of the SAT-MC and to compare their performance against
      social cognitive tests recommended for schizophrenia research. Thirty-two
      schizophrenia (SZ) and 30 substance use disorder (SUD) participants completed
      both SAT-MC forms, the Bell-Lysaker Emotion Recognition Task (BLERT), Hinting
      Task, The Awareness of Social Inference Test (TASIT), Ambiguous Intentions and
      Hostility Questionnaire (AIHQ) and questionnaire measures of interpersonal
      function. Test sensitivity, construct and external validity, test-retest
      reliability, and internal consistency were evaluated. SZ scored significantly
      lower than SUD on both SAT-MC forms, each classifying ~60% of SZ as impaired,
      compared with ~30% of SUD. SAT-MC forms demonstrated good test-retest and
      parallel form reliability, minimal practice effect, high internal consistency,
      and similar patterns of correlation with social cognitive and external validity
      measures. The SAT-MC compared favorably to recommended social cognitive tests
      across psychometric features and, with exception of TASIT, was most sensitive to
      impairment in schizophrenia when compared to a chronic substance use sample.

PMID- 29453034
TI  - Adult insecure attachment plays a role in hyperarousal and emotion dysregulation
      in Insomnia Disorder.
AB  - Studies show that unhelpful cognitive processes play a role in insomnia, whereas
      interpersonal factors have been less studied in insomnia. Attachment theory can
      be used as a cognitive-interpersonal framework for understanding insomnia.
      Because attachment insecurity (vs security) is related to psychiatric disorders
      the objective was to study the attachment style in insomnia. To this aim sixty
      four subjects with Insomnia Disorder (DSM-5) and 38 good sleepers were evaluate
      in a cross-sectional study with: Attachment Style Questionnaire (ASQ), Arousal
      Predisposition Scale (APS), Pre-Sleep Arousal Scale (PSAS) and Difficulties in
      Emotion Regulation Scale (DERS). Differences in means between groups were
      assessed using t-test or Mann-Whitney U/Wilcoxon test. Linear/multiple regression
      analyses were performed. Subjects with insomnia (mean age 47.1 + 13 yrs)
      presented an insecure attachment style and higher scores in all the scales (ASQ,
      APS, PSAS, DERS p < 0.0001) than good sleepers (mean age 48.2 + 14 yrs). After
      taking into account anxiety/depressive symptoms, insecure attachment was related
      to hyperarousal trait (p = 0.02), pre-sleep hyperarousal (p = 0.04) and emotion
      dysregulation (p = 0.002). In conclusion subjects with insomnia showed an
      insecure attachment which was related to hyperarousal trait, pre-sleep
      hyperarousal and emotion dysregulation. It may intervene in the trajectory of
      insomnia starting from predisposition to perpetuation. Clinical implications are
      discussed.

PMID- 29453035
TI  - Changes in correlation characteristics of time consumption and mind-reading
      performance in pre-onset and post-onset psychosis.
AB  - There is a strong correlation between neurocognition and social cognition.
      However, none of these studies have examined the key role of time consumption
      during social cognition tasks. Participants included 84 individuals with clinical
      high risk of psychosis (CHR), 95 healthy controls (HC), and 66 case controls
      (schizophrenia patients, SZ), who were assessed through the Reading-Mind-in-Eyes
      Tasks (RMET) with computerized recording of the response time (RT).
      Neurocognitive tests were also performed for the HC and CHR groups. A comparison
      of RMET performance revealed significantly lower scores in the SZ group compared
      to the HC group, with CHR individuals scoring between these two. However, both
      CHR and SZ subjects spent almost twice as long of the time on RMET compared to
      the HC subjects. Significant positive correlation was found between RMET accuracy
      and RT, though only in SZ patients. Taking the RT into consideration, the RMET
      performances were impacted by different neurocognition domains. Our findings
      provide new evidence about how time consumption in mind-reading may impact the
      relationship between social cognition and neurocognition, and we discuss the
      potential importance of recording the response time during social cognition
      assessment in individuals with early psychosis.

PMID- 29453036
TI  - Identifying the relative importance of non-suicidal self-injury features in
      classifying suicidal ideation, plans, and behavior using exploratory data mining.
AB  - Individuals with a history of non-suicidal self-injury (NSSI) are at alarmingly
      high risk for suicidal ideation (SI), planning (SP), and attempts (SA). Given
      these findings, research has begun to evaluate the features of this multi-faceted
      behavior that may be most important to assess when quantifying risk for SI, SP,
      and SA. However, no studies have examined the wide range of NSSI characteristics
      simultaneously when determining which NSSI features are most salient to suicide
      risk. The current study utilized three exploratory data mining techniques
      (elastic net regression, decision trees, random forests) to address these gaps in
      the literature. Undergraduates with a history of NSSI (N = 359) were administered
      measures assessing demographic variables, depression, and 58 NSSI characteristics
      (e.g., methods, frequency, functions, locations, scarring) as well as current SI,
      current SP, and SA history. Results suggested that depressive symptoms and the
      anti-suicide function of NSSI were the most important features for predicting SI
      and SP. The most important features in predicting SA were the anti-suicide
      function of NSSI, NSSI-related medical treatment, and NSSI scarring. Overall,
      results suggest that NSSI functions, scarring, and medical lethality may be more
      important to assess than commonly regarded NSSI severity indices when
      ascertaining suicide risk.

PMID- 29453037
TI  - Profile of psychiatric symptoms in methamphetamine users in China: Greater risk
      of psychiatric symptoms with a longer duration of use.
AB  - Chronic methamphetamine (MA) use is associated with psychiatric symptoms. This
      study explored pattern of co-occurring psychiatric symptoms in MA users and their
      relationship to duration of MA use. A cross-sectional study was conducted among
      MA users at the Shenzhen Compulsory Drug Detoxification Center from April 2012 to
      October 2015. The Positive and Negative Syndrome Scale, Hamilton Anxiety Scale,
      and Beck Depression Inventory were used to assess psychiatric symptoms. Among
      1277 MA users, 57.6% participants had any type of psychiatric symptoms including
      depressive, anxiety and psychotic symptoms. A dose-response relationship was
      found between duration of MA use and risk of psychiatric symptoms. The odds
      ratios (OR) of depressive symptoms increased with the duration of MA use (1-5
      years vs. < 1 year: 1.74 [95% CI, 1.24-2.42]; >= 5 years vs. < 1 year: 2.07 [1.19
      3.61]), so did the ORs of co-occurring anxiety and depressive symptoms (1-5
      years: 1.74 [1.20-2.51]; >= 5 years: 3.09 [1.76-5.40]). Methamphetamine-dependent
      individuals were four-times more likely to experience any type of psychiatric
      symptoms than non-dependent users. The prevalence of psychiatric symptoms was
      high in chronic MA users and increased with MA use duration. Early prevention and
      treatment strategies targeting both MA use and associated psychiatric symptoms
      are needed.

PMID- 29453038
TI  - Psychopathic personality traits as a form of dispositional capability for
      suicide.
AB  - The capability to enact lethal self-harm has recently been highlighted as a
      critical risk factor for suicidal behavior. Klonsky and May's (2015) three step
      theory of suicide (3ST) expanded upon the construct of the capability for suicide
      by dividing it into categories: dispositional, acquired, and practical. The
      current study examined constructs of Patrick and colleagues' (2009) triarchic
      model of psychopathy as indicators of dispositional capability in gun owners, a
      sample at heightened risk for death by suicide (Anestis and Houtsma, 2017). We
      anticipated that specific psychopathic traits would exhibit robust associations
      with other components of the capability for suicide. In a sample of 300 gun
      owning adults, Boldness was uniquely related to all indicators of practical
      capability in both male and female gun owners, and a Boldness*Meanness
      interaction predicted the highest levels of some capability components. These
      results are consistent with theoretical conceptualizations of the triarchic
      model. Our findings indicate that, among US gun owners, dispositional factors may
      impact comfort with and aptitude with guns, which may enhance our understanding
      of which gun owners are at the greatest risk of gun suicide should they develop
      suicidal thoughts.

PMID- 29453039
TI  - Tolerance for psychological pain and capability for suicide: Contributions to
      suicidal ideation and behavior.
AB  - Among people with suicide ideation most do not attempt suicide or die by suicide.
      In this online study of adult US Facebook users (n = 219), we examined capability
      for suicide, operationalized as fearlessness about death, and tolerance for
      psychological pain as potential variables that may explain why some people move
      from suicide ideation to suicidal behavior. Tolerance for psychological pain was
      significantly higher for participants who had never attempted suicide.
      Fearlessness about death was higher in participants who had attempted suicide,
      but not significantly. At high levels of psychological pain, one's belief in the
      ability to cope with psychological pain, a dimension of tolerance for
      psychological pain, was lower in participants with a history of suicide attempt
      than in participants who had never attempted suicide. The odds of suicidal desire
      were almost cut in half with each unit increase in participants' belief in their
      coping ability, whereas for each unit increase in fearlessness about death, the
      odds of suicidal desire increased by 65%. The Pearson correlation between
      tolerance for psychological pain and fearlessness about death was negligible. Our
      findings support a role for both tolerance for psychological pain and capability
      for suicide/fearlessness about death in the ideation-to-action framework of
      suicide.

PMID- 29453040
TI  - Illuminating ATOM: Taking time across the colour category border.
AB  - Walsh's A Theory Of Magnitude (ATOM) contends that we represent magnitudes such
      as number, space, time and luminance on a shared metric, such that "more" of one
      leads to the perception of "more" of the other (e.g. Walsh, 2003). In support of
      ATOM, participants have been shown to judge intervals between stimuli that are
      more discrepant in luminance as having a longer duration than intervals between
      stimuli whose luminance differs by a smaller degree (Xuan, Zhang, He, & Chen,
      2007). We tested the potential limits to the ability of luminance to influence
      duration perception by investigating the possibility that the luminance-duration
      relationship might be interrupted by a concurrent change in the colour of that
      luminance. We showed native Greek and native English speakers sequences of
      stimuli that could be either light or dark versions of green or blue. Whereas for
      both groups a shift in green luminance does not comprise a categorical shift in
      colour, for Greek speakers shifts between light and dark blue cross a colour
      category boundary (ghalazio and ble respectively). We found that duration
      judgements were neither interrupted nor inflated by a shift in colour category.
      These results represent the first evidence that the influence of luminance change
      on duration perception is resistant to interference from discrete changes within
      the same perceptual input.

PMID- 29453041
TI  - MicroRNA signature of regulatory T cells in health and autoimmunity.
AB  - MicroRNAs (miRNAs) are small RNA molecules with regulatory functions on the
      expression of genes through binding directly to target messenger RNA (mRNA)
      transcripts, eventuating in gene expression suppression via translational
      hindrance and/or target mRNA cleavage. These molecules have been established to
      participate in numerous critical cellular settings, including differentiation,
      development, and function of immune cells. As an important suppressor cell of
      immune system, regulatory T cells (Tregs) are important in modulating the immune
      homeostasis as well as tolerance to self-antigens. Despite identification of
      numerous transcription factors, cytokines, and other mediators regulate the
      biology of Tregs, investigations have demonstrated that noncoding RNAs are
      involved in several mechanisms of the regulation of Treg cells. On the other
      side, dysregulation of expression of several miRNAs has been reported in Tregs,
      implicating to the impaired function of these regulatory cells, resulting in
      autoimmune and other immune-based disorders. In this review, we aim to go through
      the overall microRNA network and specific miRNAs that are involved in the
      development, differentiation, and function of Tregs. Moreover, an overview was
      provided with respect to the role of aberrant expression of miRNAs in Tregs of
      autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus,
      rheumatoid arthritis, inflammatory bowel disease, diabetes, and psoriasis.

PMID- 29453042
TI  - Evaluation of the anti-hypertensive effect of Tengfu Jiangya tablet by
      combination of UPLC-Q-exactive-MS-based metabolomics and iTRAQ-based proteomics
      technology.
AB  - OBJECTIVE: Tengfu Jiangya tablet (TJT) is a traditional Chinese medicine
      formulation composed of Uncaria rhynchophylla and Semen raphani. It is a hospital
      preparation that is widely used in clinics for treating hypertension. A previous
      metabolomics study reported that TJT exerted a protective effect on hypertension
      by restoring impaired NO production, ameliorating the inflammatory state, and
      vascular remodeling. A clinical proteomics study also revealed five key target
      proteins during TJT intervention. This study aimed to integrate proteome and
      metabolome data sets for a holistic view of the molecular mechanisms of TJT in
      treating hypertension. METHODS: Serum samples from spontaneously hypertensive
      rats and Wistar Kyoto rats were analyzed using ultra-high performance liquid
      chromatography coupled to Q Exactive hybrid quadrupole-Orbitrap mass spectrometry
      (UPLC-Q-Exactive-MS)-based metabolomics technology and isobaric tags for relative
      and absolute quantitation (iTRAQ)-based quantitative proteomics technology.
      Moreover, we selected two candidate proteins and determined their expression
      levels in rat serum using an enzyme-linked immunosorbent assay (ELISA). RESULTS:
      A total of 20 potential biomarkers and 14 differential proteins in rat serum were
      identified. These substances were mainly involved in three biological pathways:
      the kallikrein-kinin pathway, the lipid metabolism pathway, and the PPARgamma
      signaling pathway. CONCLUSIONS: The results suggested that TJT could effectively
      treat hypertension, partially by regulating the above three metabolic pathways.
      The combination of proteomics and metabolomics provided a feasible method to
      uncover the underlying interventional effect and therapeutic mechanism of TJT on
      spontaneously hypertensive rats.

PMID- 29453043
TI  - Understanding of human ATP binding cassette superfamily and novel multidrug
      resistance modulators to overcome MDR.
AB  - Indeed, multi-drug resistance (MDR) is a significant obstacle to effective
      chemotherapy. The overexpression of ATP-binding cassette (ABC) membrane
      transporters is a principal cause of enhanced cytotoxic drug efflux and treatment
      failure in various types of cancers. At cellular level, the pumps of ABC family
      regulate the transportation of numerous substances including drugs in and out of
      the cells. In past, the overexpression of ABC pumps suggested a well-known
      mechanism of drug resistance in cancers as well as infectious diseases. In
      oncology, the search for new compounds for the inhibition of these hyperactive
      ABC pumps either genetically or functionally, growing interest to reverse multi
      drug resistance and increase chemotherapeutic effects. Several ABC pump
      inhibitor/modulators has been explored to address the cancer associated MDR.
      However, the clinical results are still disappointing and conventional
      chemotherapies are constantly failed in successful eradication of MDR tumors. In
      this context, the structural and functional understanding of different ATP pumps
      is most important. In this concise review, we elaborated basic crystal structure
      of ABC transporter proteins as well as its critical elements such as different
      domains, motifs as well as some important amino acids which are responsible for
      ATP binding and drug efflux as well as demonstrated an ATP-switch model employed
      by various ABC membrane transporters. Furthermore, we briefly summarized
      different newly identified MDR inhibitors/modulators, deployed alone or in
      combination with cytotoxic agents to deal with MDR in different types of cancers.

PMID- 29453044
TI  - Micro RNA-1298 opposes the effects of chronic oxidative stress on human
      trabecular meshwork cells via targeting on EIF4E3.
AB  - OBJECTIVE: This study aimed to investigate the effect and potential mechanism of
      miR-1298 in the progression of human trabecular meshwork (HTM) cells. MATERIAL
      AND METHODS: Expression of miR-1298 was assessed by quantitative real time PCR
      (qRT-PCR), as well as in HTM-1 and HTM-2 cells. Mature miR-1298 mimic, miR-1298
      inhibitor, and si-EIF4E3 and their corresponding controls were transfected into
      HTM-1 and HTM-2 to obtain stable HTM cells. Luciferase reporter assay was used to
      verify regulation between miR-1298 and EIF4E3. Cytotoxicity and Oxidative damage
      were assessed using commercial kits, and apoptosis was determined using flow
      cytometry. ECM and apoptosis related factors were determined using qRT-PCR and
      western blotting, as well as the pathway related factors. RESULTS: The expression
      of miR-1298 was significantly decreased both in glaucoma and HTM cells. MiR-1298
      mimic could significantly inhibit the increase of cytotoxicity, apoptosis,
      accumulation of carbonylated proteins and ECM induced by COS, but miR-1298
      inhibitor could obviously promote the increase effects caused by COS in HTM
      cells. EIF4E3 was a downstream target of miR-1298. Sliced EIF4E3 could
      significantly inhibit the increase effects induced miR-1298 inhibitor in HTM
      cells under COS. The expression levels of TGF-beta2 and Smad4 were significantly
      increased, and Wnt3a and beta-cantenin were obviously decreased under COS, and
      miR-1298 inhibitor could markedly promote this increase effect, while sliced
      EIF4E3 could reverse the effect of miR-1298 under COS. CONCLUSIONS: miR-1298
      could protect HTM cells to against damage caused by COS via inhibiting TGF
      beta2/Smad4 pathway and activating canonical Wnt pathway.

PMID- 29453045
TI  - Activation of PPARgamma mediates icaritin-induced cell cycle arrest and apoptosis
      in glioblastoma multiforme.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is the most prevalent primary
      malignancy of the brain. This study was designed to investigate whether icaritin
      exerts anti-neoplastic activity against GBM in vitro. MATERIALS AND METHODS: Cell
      Counting Kit-8 (CCK-8) assay was utilized to examine the viability of GBM cells.
      The apoptotic cell population was measured by flow cytometry analysis. Cell cycle
      distribution was detected by flow cytometry as well. Western blot analysis was
      performed to examine the level of biomarker proteins in GBM cells. Levels of
      PPARgamma mRNA and protein were detected by qPCR and western blot analysis,
      respectively. To examine the role of PPARgamma in the anti-neoplastic activity of
      icaritin, PPARgamma antagonist GW9662 or PPARgamma siRNA was used. The activity
      of PPARgamma was determined by DNA binding and luciferase assays. RESULTS: Our
      findings revealed that icaritin markedly suppresses cell growth in a dose
      dependent and time-dependent fashion. The cell population at the G0/G1 phase of
      the cell cycle was significantly increased following icaritin treatment.
      Meanwhile, icaritin promoted apoptotic cell death in T98G and U87MG cells.
      Further investigation showed upregulation of PPARgamma played a key role in the
      anti-neoplastic activities of icaritin. Moreover, our result demonstrated
      activation of AMPK signaling by icaritin mediated the modulatory effect of
      icaritin on PPARgamma. CONCLUSION: Our results suggest the PPARgamma may mediate
      anti-neoplastic activities against GBM.

PMID- 29453046
TI  - Molecular chemoprevention by morin - A plant flavonoid that targets nuclear
      factor kappa B in experimental colon cancer.
AB  - Colorectal cancer is the third most common cancer worldwide. The development of
      effective, inexpensive and safe chemopreventive agents would be of great benefit
      as it involves use of natural products to prevent or suppress the progression of
      precursor lesions. Morin a flavonoid found in figs (Ficus carica) and other
      plants is shown to inhibit 1,2-dimethylhydrazine (DMH) induced colon cancer
      progression in a short term and long term model of colon cancer rats; however,
      the molecular target for the colon cancer chemoprotective efficacy of morin is
      yet to be discovered. The present study aims to explore the molecular basis of
      how morin contributes to the chemoprevention with a focus on NF-kappaB signaling
      pathway. The effect of morin on NF-kappaB signaling in DMH-induced carcinogenic
      events such as inflammation and apoptosis were analyzed by studying the
      histopathological analysis using Hematoxylin and Eosin staining (H &E), mRNA
      expression using q-PCR, protein expression using Immunohistochemistry (IHC) and
      western blot. Morin supplementation to DMH administered rats down regulated NF
      kappaB pathway and its downstream inflammatory mediators like tumor necrosis
      factor alpha (TNF-alpha), interleukin 6 (IL-6), cyclooxygenase 2 (COX-2) and
      prostaglandin (PGE-2). Morin supplementation to DMH administered rats alters
      BAX/BCL2 ratio favoring apoptosis in carcinogen treated rats. Our findings
      explored that molecular chemoprevention of morin targets NF-kappaB and acts as a
      potent anti-inflammatory and pro-apoptotic agent for colon cancer prevention.

PMID- 29453047
TI  - Influence of potassium hydroxide activation on characteristics and environmental
      risk of heavy metals in chars derived from municipal sewage sludge.
AB  - To investigate the influence of KOH activation on characteristics and
      environmental risk of heavy metals in chars, sludge was pyrolyzed with varying
      amount of KOH. The analyzation of characteristics and potential ecological risk
      evaluation of heavy metals were conducted by surface area analyzer, FTIR, XRD and
      BCR sequential extraction. The activated chars have higher surface area and lower
      content of silica compared to those without being activated. The activation of
      KOH promoted residual fraction of Cd, meanwhile, Zinc, Cr, Ni and Mn were
      converted to relatively unstable fractions (F2 and F3). The results of risk
      assessment indicated that the potential ecological risk level of Cd was reduced
      in activated chars, while risk level of Zn, Cr, Ni and Mn were increased after
      pyrolysis with KOH activation. The potential ecological risk of heavy metals in
      activated chars was further declined, and the risk level transformed from
      moderate to low.

PMID- 29453048
TI  - A system composed of a biofilm electrode reactor and a microbial fuel cell
      constructed wetland exhibited efficient sulfamethoxazole removal but induced sul
      genes.
AB  - The aim of this work was to study sulfamethoxazole (SMX) removal efficiency and
      fate of corresponding sul genes in a stacked microbial fuel cell-constructed
      wetland coupled biofilm electrode reactor system (MFC-CW-BER). Findings showed
      that two stacked MFC-CWs could provide a relatively stable electricity supply to
      support the biofilm for SMX removal. Excellent SMX removal (>99.29%) was obtained
      in the BER-MFC-CW. Compared with the 2000 ug L-1 SMX influent, the relative
      abundance of the sul genes in biofilm media and effluent was enhanced with
      continuously high concentrations of SMX (4000 MUg L-1). The relative abundances
      of sul genes in biofilm media and effluent increased as the hydraulic retention
      time decreased. However, there was no obvious variation in the relative abundance
      of sul genes in the effluent from MFC-CWs. No effect could be observe of the
      direct voltage and bioelectricity on the relative abundance of the sul genes in
      the BER.

PMID- 29453049
TI  - One-step conversion of agro-wastes to nanoporous carbons: Role in separation of
      greenhouse gases.
AB  - Highly microporous carbons have been synthesized from four types of agro-wastes
      of lignin, walnut shells, orange peels and apricot seeds by one-step
      carbonization/activation with potassium hydroxide (KOH) in varying ratios. The
      resultant carbons demonstrated BET specific surface areas of 727-2254 m2/g, and
      total pore volumes 0.34-1.14 cm3/g. These are higher than the majority of agro
      waste derived carbons reported in the literature. For all the carbons, CO2
      adsorption at 298 K was higher than SF6 followed by N2 suggesting a possible
      separation of CO2 and SF6 from N2. The adsorbed amounts of CO2 at 298 K and 273 K
      and at pressures up to 760 Torr were 7.24 and 9.4 mmol/g, respectively which, to
      the best of our knowledge, are the highest CO2 uptakes in these temperatures by
      any carbon material reported so far. For all the gases, selectivity, mixed
      adsorption isotherms and adsorption breakthrough have been simulated from
      experimental data.

PMID- 29453050
TI  - Enhancement in the aromatic yield from the catalytic fast pyrolysis of rice straw
      over hexadecyl trimethyl ammonium bromide modified hierarchical HZSM-5.
AB  - Modified H-type ZSM-5 (HZSM-5) catalysts were prepared using hexadecyl trimethyl
      ammonium bromide (CTAB) as mesopore templates to enhance the activity for the
      catalytic fast pyrolysis of rice straw for aromatics compounds. A certain
      quantity of CTAB added into the HZSM-5 (HZ) forming hierarchical structure
      exhibited an improvement in the yield of the aromatics and a decrease in the
      yield of coke in comparison with that of bare HZ. In contrast, excessive CTAB
      addition resulted in a decrease in aromatic yield and an increase in coke yield.
      The effects of crystallinity, textural properties, morphological structure and
      acidity distribution on the production of aromatic compounds were measured by
      XRD, BET, TEM and NH3-TPD. The good crystallinity, small amount of mesopore
      formation and highest total acidity discovered in HZ-0.01 (the mole ratio of
      CTAB/SiO2 is 0.01) provided the highest aromatic compound yield of 26.8% and the
      lowest coke yield of 39.2%.

PMID- 29453051
TI  - HNO3 modified biochars for uranium (VI) removal from aqueous solution.
AB  - The HNO3 treatment was used to chemically modify the biochars produced from wheat
      straw (WH) and cow manure for U(VI) removal from aqueous solution. Macroscopic
      experiments proved that the enrichment of U(VI) on the biochars was regulated by
      surface complexation and electrostatic interactions. FTIR and XPS analyses
      confirmed that the highly efficient adsorption of U(VI) was due to the carboxyl
      groups on the biochar surfaces. The reducing agents of the R-CH2OH groups
      facilitated U(VI) adsorption on the untreated biochars. Owing to the higher
      contents of surface COO groups and more negative surface charge, the modified
      biochars showed enhanced U(VI) adsorption ability than the untreated ones. The
      maximum adsorption capacity of U(VI) by the oxidized WH was calculated to be
      355.6 mg/g at pH 4.5 and 298 K, which was an improvement of 40 times relative to
      the untreated WH and was higher than that of most carbon-based adsorbents.

PMID- 29453052
TI  - Ac-LVFFARK-NH2 conjugation to beta-cyclodextrin exhibits significantly enhanced
      performance on inhibiting amyloid beta-protein fibrillogenesis and cytotoxicity.
AB  - Inhibition of amyloid beta-protein (Abeta) aggregation is of significance for the
      potential treatment of Alzheimer's disease. We have herein conjugated
      heptapeptide Ac-LVFFARK-NH2 (LK7) to beta-cyclodextrin (betaCyD) and studied the
      inhibitory effect of the LK7-betaCyD conjugate on Abeta aggregation. The
      conjugation significantly improved the peptide solubility and suppressed the self
      assembly propensity. This led to 30% increase of the binding affinity of LK7 for
      Abeta in the conjugate due to increased hydrophobic interactions. Thus, LK7
      betaCyD suppressed the conformational transition of Abeta and showed stronger
      inhibitory effect on Abeta fibrillation than LK7. Thus, LK7-betaCyD exhibited
      protective effect on Abeta40-induced cytotoxicity, and the cells completely
      survived at 10 molar excess of LK7-betaCyD (from 67% to 100%). By contrast, LK7
      showed only a moderate inhibition on Abeta fibrillation, and could not inhibit
      the amyloid cytotoxicity. The research proved that conjugation of hydrophobic
      peptide to betaCyD was promising to increase its inhibition potency against Abeta
      aggregation.

PMID- 29453053
TI  - Ultrasound molecular imaging of acute cardiac transplantation rejection using
      nanobubbles targeted to T lymphocytes.
AB  - Clinical surveillance of acute heart transplantation rejection requires repeated
      invasive endomyocardial biopsies and noninvasive diagnostic techniques are
      desperately needed. It is acknowledged that T lymphocyte infiltration is the
      central process of acute rejection. We hypothesized that ultrasound molecular
      imaging with T lymphocyte-targeted nanobubbles could be used to detect acute
      rejection in heart transplantation. In this study, nanobubbles bearing anti-CD3
      antibody (NBCD3) or isotype antibody (NBcon) were prepared and characterized.
      There was significant adhesion of NBCD3 to T lymphocytes compared with NBconin
      vitro. The signal intensity of the adherent NBCD3 was significantly higher than
      that of the NBcon in allograft rats, but not significantly different in isograft
      rats. Furthermore, the signal intensity of NBCD3 in allograft rats was
      significantly higher than that in isograft rats, indicating more T lymphocyte
      infiltration in allograft rats compared with isograft rats. These results were
      further confirmed by immunohistochemistry examination, and the signal intensity
      of NBCD3 was positively correlated with the number of T lymphocytes in allograft
      rats. In summary, ultrasound molecular imaging with T lymphocyte-targeted
      nanobubbles can detect T lymphocyte infiltration in acute rejection and could be
      used as a noninvasive method in acute rejection detection after cardiac
      transplantation.

PMID- 29453054
TI  - Determining the number of contributors to DNA mixtures in the low-template
      regime: Exploring the impacts of sampling and detection effects.
AB  - The interpretation of DNA evidence may rely upon the assumption that the forensic
      short tandem repeat (STR) profile is composed of multiple genotypes, or partial
      genotypes, originating from n contributors. In cases where the number of
      contributors (NOC) is in dispute, it may be justifiable to compute likelihood
      ratios that utilize different NOC parameters in the numerator and denominator, or
      present different likelihoods separately. Therefore, in this work, we evaluate
      the impact of allele dropout on estimating the NOC for simulated mixtures with up
      to six contributors in the presence or absence of a major contributor. These
      simulations demonstrate that in the presence of dropout, or with the application
      of an analytical threshold (AT), estimating the NOC using counting methods was
      unreliable for mixtures containing one or more minor contributors present at low
      levels. The number of misidentifications was only slightly reduced when we expand
      the number of STR loci from 16 to 21. In many of the simulations tested herein,
      the minimum and actual NOC differed by more than two, suggesting that low
      template, high-order mixtures with allele counts fewer than six may be
      originating from as many as four-, five-, or six-persons. Thus, there is
      justification for the use of differing or multiple assumptions on the NOC when
      computing the weight of DNA evidence for low-template mixtures, particularly when
      the peak heights are in the vicinity of the signal threshold or allele counting
      methods are the mechanism by which the NOC is assessed.

PMID- 29453055
TI  - Enhanced electrosynthesis performance of Moorella thermoautotrophica by improving
      cell permeability.
AB  - Microbial electrosynthesis systems (MES) are promising devices in which microbes
      obtain electrons from electrodes to produce extracellular multicarbon compounds.
      This study investigates whether improvement in cell permeability can enhance
      electrosynthesis performance of Gram-positive Moorella thermoautotrophica in MES.
      Results showed that when <=30mg/L penicillin was added, the cell permeability was
      doubled, and the electron uptake per biomass (including both cathode-associated
      biomass and suspended biomass) was 1.84 times that of the control, while formate
      and acetate production rates per biomass were 1.96 and 2.23 times those of the
      control, respectively. Enhanced cell permeability caused higher redox activities
      of outmost cytochrome C and increased release of redox electron shuttles, both of
      which were beneficial to extracellular electron uptake. Coulombic efficiencies
      increased from 73%+/-3% to 88%+/-3% with better cell permeability, demonstrating
      that higher proportion of electrical energy recovered in the chemical-production
      reaction. This research demonstrates that making a moderate decrease in
      peptidoglycan of cell walls to improve cell permeability can enhance electron
      uptakes and chemical production rates of Gram-positive microbes in MES, which
      would serve as a base for the future genetic modification study of superior
      electrosynthesis strains.

PMID- 29453056
TI  - Biological properties of Beet soil-borne mosaic virus and Beet necrotic yellow
      vein virus cDNA clones produced by isothermal in vitro recombination: Insights
      for reassortant appearance.
AB  - Two members of the Benyviridae family and genus Benyvirus, Beet soil-borne mosaic
      virus (BSBMV) and Beet necrotic yellow vein virus (BNYVV), possess identical
      genome organization, host range and high sequence similarity; they infect Beta
      vulgaris with variable symptom expression. In the US, mixed infections are
      described with limited information about viral interactions. Vectors suitable for
      agroinoculation of all genome components of both viruses were constructed by
      isothermal in vitro recombination. All 35S promoter-driven cDNA clones allowed
      production of recombinant viruses competent for Nicotiana benthamiana and Beta
      macrocarpa systemic infection and Polymyxa betae transmission and were compared
      to available BNYVV B-type clone. BNYVV and BSBMV RNA1 + 2 reassortants were
      viable and spread long-distance in N. benthamiana with symptoms dependent on the
      BNYVV type. Small genomic RNAs were exchangeable and systemically infected B.
      macrocarpa. These infectious clones represent a powerful tool for the
      identification of specific molecular host-pathogen determinants.

PMID- 29453057
TI  - Mammarenaviruses deleted from their Z gene are replicative and produce an
      infectious progeny in BHK-21 cells.
AB  - Mammarenaviruses bud out of infected cells via the recruitment of the endosomal
      sorting complex required for transport through late domain motifs localized into
      their Z protein. Here, we demonstrated that mammarenaviruses lacking this protein
      can be rescued and are replicative, despite a 3-log reduction in virion
      production, in BHK-21 cells, but not in five other cell lines. Mutations of
      putative late domain motifs identified into the viral nucleoprotein resulted in
      the almost complete abolition of infectious virion production by Z-deleted
      mammarenaviruses. This result strongly suggested that the nucleoprotein may
      compensate for the deletion of Z. These observations were primarily obtained
      using the Lymphocytic choriomeningitis virus, and further confirmed using the Old
      World Lassa and New World Machupo viruses, responsible of human hemorrhagic
      fevers. Z-deleted viruses should prove very useful tools to investigate the
      biology of Mammarenaviruses.

PMID- 29453058
TI  - Antigenic and genetic evolution of contemporary swine H1 influenza viruses in the
      United States.
AB  - Several lineages of influenza A viruses (IAV) currently circulate in North
      American pigs. Genetic diversity is further increased by transmission of IAV
      between swine and humans and subsequent evolution. Here, we characterized the
      genetic and antigenic evolution of contemporary swine H1N1 and H1N2 viruses
      representing clusters H1-alpha (1A.1), H1-beta (1A.2), H1pdm (1A.3.3.2), H1-gamma
      (1A.3.3.3), H1-delta1 (1B.2.2), and H1-delta2 (1B.2.1) currently circulating in
      pigs in the United States. The delta1-viruses diversified into two new genetic
      clades, H1-delta1a (1B.2.2.1) and H1-delta1b (1B.2.2.2), which were also
      antigenically distinct from the earlier H1-delta1-viruses. Further
      characterization revealed that a few key amino acid changes were associated with
      antigenic divergence in these groups. The continued genetic and antigenic
      evolution of contemporary H1 viruses might lead to loss of vaccine cross
      protection that could lead to significant economic impact to the swine industry,
      and represents a challenge to public health initiatives that attempt to minimize
      swine-to-human IAV transmission.

PMID- 29453059
TI  - Lessons learned from research and surveillance directed at highly pathogenic
      influenza A viruses in wild birds inhabiting North America.
AB  - Following detections of highly pathogenic (HP) influenza A viruses (IAVs) in wild
      birds inhabiting East Asia after the turn of the millennium, the intensity of
      sampling of wild birds for IAVs increased throughout much of North America. The
      objectives for many research and surveillance efforts were directed towards
      detecting Eurasian origin HP IAVs and understanding the potential of such viruses
      to be maintained and dispersed by wild birds. In this review, we highlight five
      important lessons learned from research and surveillance directed at HP IAVs in
      wild birds inhabiting North America: (1) Wild birds may disperse IAVs between
      North America and adjacent regions via migration, (2) HP IAVs can be introduced
      to wild birds in North America, (3) HP IAVs may cross the wild bird-poultry
      interface in North America, (4) The probability of encountering and detecting a
      specific virus may be low, and (5) Population immunity of wild birds may
      influence HP IAV outbreaks in North America. We review empirical support derived
      from research and surveillance efforts for each lesson learned and, furthermore,
      identify implications for future surveillance efforts, biosecurity, and
      population health. We conclude our review by identifying five additional areas in
      which we think future mechanistic research relative to IAVs in wild birds in
      North America are likely to lead to other important lessons learned in the years
      ahead.

PMID- 29453060
TI  - Effect of selenium on Penaeus monodon and Perna viridis: Enzyme activities and
      histopathological responses.
AB  - The study was carried out to evaluate enzyme activities and histopathological
      changes due to the effect of acute and chronic definitive toxicity of selenium
      (Se) on the post larvae (PL) of giant tiger shrimp (Penaeus monodon), and green
      mussel (Perna viridis). The 96-h Median Lethal concentration (LC50) for the PL of
      shrimp was 3.36 mg L-1 and the chronic value for the long-term survival endpoint
      in a 21-d exposure was 0.10 mg L-1. The green mussel 96-h LC50 was 28.41 mg L-1
      and the chronic value for the long-term survival endpoint in a 30-d exposure was
      3.06 mg L-1. Native polyacrylamide gel electrophoresis revealed altered diverse
      isoforms of esterase, superoxide dismutase and malate dehydrogenase activities in
      the PL of shrimp and green mussel exposed to sublethal concentration of Se.
      Cellular anomalies such as deformation and fusion of corneal cells, detachment of
      corneal cells from cornea facet and increased space between ommatidia were
      observed in the compound eye of PL of shrimp exposed to Se for 21-d. Shrinkage
      and clumping of mucous gland, degenerative changes in phenol gland, and ciliated
      epithelium were observed in the foot of green mussel exposed to Se for 30-d. This
      study shows that cellular anomalies in the compound eye of PL of P. monodon and
      foot tissues of P. viridis described would affect the vision of shrimp and byssus
      thread formation in green mussel.

PMID- 29453061
TI  - Effect of U(VI) aqueous speciation on the binding of uranium by the cell surface
      of Rhodotorula mucilaginosa, a natural yeast isolate from bentonites.
AB  - This study presents the effect of aqueous uranium speciation (U-hydroxides and U
      hydroxo-carbonates) on the interaction of this radionuclide with the cells of the
      yeast Rhodotorula mucigilanosa BII-R8. This strain was isolated from Spanish
      bentonites considered as reference materials for the engineered barrier
      components of the future deep geological repository of radioactive waste. X-ray
      absorption and infrared spectroscopy showed that the aqueous uranium speciation
      has no effect on the uranium binding process by this yeast strain. The cells bind
      mobile uranium species (U-hydroxides and U-hydroxo-carbonates) from solution via
      a time-dependent process initiated by the adsorption of uranium species to
      carboxyl groups. This leads to the subsequent involvement of organic phosphate
      groups forming uranium complexes with a local coordination similar to that of the
      uranyl mineral phase meta-autunite. Scanning transmission electron microscopy
      with high angle annular dark field analysis showed uranium accumulations at the
      cell surface associated with phosphorus containing ligands. Moreover, the effect
      of uranium mobile species on the cell viability and metabolic activity was
      examined by means of flow cytometry techniques, revealing that the cell
      metabolism is more affected by higher concentrations of uranium than the cell
      viability. The results obtained in this work provide new insights on the
      interaction of uranium with bentonite natural yeast from genus Rhodotorula under
      deep geological repository relevant conditions.

PMID- 29453062
TI  - Heavy metal accumulation, risk assessment and integrated biomarker responses of
      local vegetables: A case study along the Le'an river.
AB  - In this research, Ganzhou Chinese Cabbage (Brassica rapa pekinensis), Native
      Purple Garlic (Allium sativum L) and Leping Radish (Raphanus sativus L) widely
      planted and distributed along the Le'an River were chosen in the present study.
      Soil physical-chemical properties, nutrients contents as well as heavy metals
      elements accumulated in both soils and vegetables collected from 24 sites were
      analyzed by lab analysis combined with statistical method which was also used for
      calculation of contamination factor, pollution indexes and hazardous index. Heavy
      metals accumulation in soils were revealed with higher level, and copper and
      cadmium exceeded the background values by 8.82 and 16.73 times on average, which
      were also significantly related with the distribution of nonferrous metal
      processing enterprises. Heavy metal elements accumulated in vegetables were fully
      consistent with the finding of pollution characteristics in soils. Peroxidase
      biomarkers in vegetables, including superoxide dismutase (SOD), catalase (CAT),
      peroxidase (POD), reduced glutathione (GSH) and lipoperoxidation (as TBARS), as
      well as integrated biomarker responses (IBR) were determined to give a reliable
      response after exposing of contaminants. Heavy metals accumulation ability and
      biomarker responses for three vegetables were usually determined in the following
      decrease trend: Ganzhou Chinese Cabbage > Native Purple Garlic > Leping Radish.
      Compared with peroxidase biomarkers activities or contents of control site, all
      the measured biomarkers in polluted sites showed significantly responses,
      indicating potential relationship between pollutants stresses and biomarker
      responses. This study also revealed that the IBR values were coordinated well
      with the pollutants concentrations.

PMID- 29453063
TI  - 1H NMR-based metabolomics reveals interactive effects between the carrier solvent
      methanol and a pharmaceutical mixture in an amphibian developmental bioassay with
      Limnodynastes peronii.
AB  - Organic carrier solvents are used in aquatic toxicity testing to improve chemical
      solubility and facilitate the exploration of dose-response relationships. Both
      water- and solvent-control groups are normally included in these scenarios to
      ensure that the solvent itself has no effect on the test organism, but this fails
      to consider possible interactive effects between carrier solvents and
      contaminants of interest. We explored this topic by exposing Limnodynastes
      peronii tadpoles to a mixture of common water-soluble pharmaceuticals
      (diclofenac, metformin and valproic acid) in the presence and absence of the
      carrier solvent methanol, according to standard developmental bioassay
      methodology. Nuclear Magnetic Resonance (NMR) spectroscopy was applied as a
      platform for untargeted metabolomics, to compare broad sub-lethal hepatotoxicity
      in solvent- and solvent-free exposure scenarios. Considerable interactive effects
      were identified between the pharmaceutical mixture and a typical dose of methanol
      (0.003%). Specifically, pronounced differences were observed between the solvent-
      and solvent-free exposure groups for leucine, acetate, glutamine, citrate,
      glycogen, tyrosine, arginine, purine nucleotides and an unidentified metabolite
      at 6.53 ppm. Various other metabolites exhibited similar disparity related to the
      use of carrier solvent, but the interactions were non-significant. These results
      raise important questions about the use of carrier solvents for chemical
      exposures in aquatic ecotoxicology, and particularly for studies interested in
      sub-lethal mechanistic information and/or biomarker discovery.

PMID- 29453064
TI  - Levels, sources, and potential human health risks of PCNs, PCDD/Fs, and PCBs in
      an industrial area of Shandong Province, China.
AB  - Polychlorinated naphthalenes (PCNs), polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs), and polychlorinated biphenyls (PCBs) are of public
      concern worldwide because of their persistence and toxicity. To address the human
      health risks of these pollutants and identify possible sources, soil samples were
      collected from an industrial area and surrounding residential area in Shandong
      Province, China. The PCN, PCDD/F, and PCB levels in these samples were
      determined. Extremely high concentrations of PCNs were detected in two soil
      samples, and their congener distributions were similar to those of a PCN
      industrial technical product. The levels of combustion-related PCNs and PCDD/Fs
      were high in samples collected near a secondary copper smelter. The distribution
      of total PCB concentrations was similar to that of PCNs. Both historical residues
      from industrial technical products and emissions from the secondary copper
      smelter were likely sources of PCNs and PCBs, whereas emissions from the smelter
      were the main source of PCDD/Fs. A soil sample from near the smelter had a high
      SigmaTEQ concentration (PCDD/Fs + PCBs + PCNs = 18.33 pg TEQ/g) and carcinogenic
      risk (0.85 * 10-6) to workers. For all the other samples, the levels of PCDD/Fs,
      PCBs and PCNs exhibited low carcinogenic and noncarcinogenic risks to workers and
      residents.

PMID- 29453065
TI  - Transcriptomic analysis of boron hyperaccumulation mechanisms in Puccinellia
      distans.
AB  - Puccinellia distans, common alkali grass, is found throughout the world and can
      survive in soils with boron concentrations that are lethal for other plant
      species. Indeed, P. distans accumulates very high levels of this element. Despite
      these interesting features, very little research has been performed to elucidate
      the boron tolerance mechanism in this species. In this study, P. distans samples
      were treated for three weeks with normal (0.5 mg L-1) and elevated (500 mg L-1)
      boron levels in hydroponic solution. Expressed sequence tags (ESTs) derived from
      shoot tissue were analyzed by RNA sequencing to identify genes up and down
      regulated under boron stress. In this way, 3312 differentially expressed
      transcripts were detected, 67.7% of which were up-regulated and 32.3% of which
      were down-regulated in boron-treated plants. To partially confirm the RNA
      sequencing results, 32 randomly selected transcripts were analyzed for their
      expression levels in boron-treated plants. The results agreed with the expected
      direction of change (up or down-regulation). A total of 1652 transcripts had
      homologs in A. thaliana and/or O. sativa and mapped to 1107 different proteins.
      Functional annotation of these proteins indicated that the boron tolerance and
      hyperaccumulation mechanisms of P. distans involve many transcriptomic changes
      including: alterations in the malate pathway, changes in cell wall components
      that may allow sequestration of excess boron without toxic effects, and increased
      expression of at least one putative boron transporter and two putative
      aquaporins. Elucidation of the boron accumulation mechanism is important in
      developing approaches for bioremediation of boron contaminated soils.

PMID- 29453066
TI  - Synthesis of a stable magnesium-impregnated biochar and its reduction of
      phosphorus leaching from soil.
AB  - Biochar improves soil fertility and promotes long-term terrestrial carbon
      sequestration. However, biochar seems not to be stable enough due to physical,
      chemical and biological reactions. In this study, a novel, stable, and magnesium
      (Mg)-impregnated biochar was prepared from cow dung and applied to decrease P
      leaching from soil. XPS, FTIR, XRD, SEM and EDS were used to evaluate the effect
      of modification and phosphorus(P) sorption on the oxidation resistance of
      biochar. The results showed that the oxidation resistance of the Mg-impregnated
      biochar was improved by the formation of MgO on its surface. The soil column
      experiment indicated that the Mg-impregnated -biochar decreased P loss from
      leaching by 89.25%. In addition, the available P content of the soil surface
      layer under Mg-impregnated biochar treatment increased by 3.5-fold relative to
      that under the control treatment. P sorption also enhanced the oxidation
      resistance of biochar. The relative contents of CO, CO, and COOH on the surface
      of P-laden biochar was 20.97% and was lower than those on the surface of biochar
      without P sorption (33.15%). Oxidation resistance was enhanced by the formation
      of new MgP crystals, which prevented the oxidation of CC, CC, and CH into CO, CO,
      and COOH, respectively, by acting as a physical barrier between the biochar
      surface and oxygen. The results of XRD, SEM and EDS provided evidence for the
      formation of MgP crystals. Overall, results indicated that the Mg-impregnated
      biochar can reduce P leaching loss from soil and has enhanced stability.

PMID- 29453067
TI  - Applying no-depletion equilibrium sampling and full-depletion bioaccessibility
      extraction to 35 historically polycyclic aromatic hydrocarbon contaminated soils.
AB  - Assessing the bioaccessibility of organic pollutants in contaminated soils is
      considered a complement to measurements of total concentrations in risk
      assessment and legislation. Consequently, methods for its quantification require
      validation with historically contaminated soils. In this study, 35 such soils
      were obtained from various locations in Switzerland and Cuba. They were exposed
      to different pollution sources (e.g., pyrogenic and petrogenic) at various
      distance (i.e., urban to rural) and were subject to different land use (e.g.,
      urban gardening and forest). Passive equilibrium sampling with polyoxymethylene
      was used to determine freely dissolved concentrations (Cfree) of polycyclic
      aromatic hydrocarbons (PAHs), while sorptive bioaccessibility extraction (SBE)
      with silicone rods was used to determine the bioaccessible PAH concentrations
      (Cbioacc) of these soils. The organic carbon partition coefficients of the soils
      were highest for skeet soils, followed by traffic, urban garden and rural soils.
      Lowest values were obtained from soil exposed to petrogenic sources.
      Applicability of SBE to quantify Cbioacc was restricted by silicone rod sorption
      capacity, as expressed quantitatively by the Sorption Capacity Ratio (SCR);
      particularly for soils with very high KD. The source of contamination determined
      bioaccessible fractions (fbioacc). The smallest fbioacc were obtained with skeet
      soils (15%), followed by the pyrogenically influenced soils, rural soils, and
      finally, the petrogenically contaminated soil (71%). In conclusion, we present
      the potential and limitations of the SBE method to quantify bioaccessibility in
      real soils. These results can be used for additional development of this and
      similar bioaccessibility methods to guarantee sufficient sorption capacity to
      obtain reliable results.

PMID- 29453068
TI  - Effect of selenium-enriched organic material amendment on selenium fraction
      transformation and bioavailability in soil.
AB  - To exploit the plant byproducts from selenium (Se) biofortification and reduce
      environmental risk of inorganic Se fertilizer, pot experiment was conducted in
      this study. The effects of Se-enriched wheat (Triticum aestivum L.) straw (WS +
      Se) and pak choi (Brassica chinensis L.) (P + Se) amendment on organo-selenium
      speciation transformation in soil and its bioavailability was evaluated by pak
      choi uptake. The Se contents of the cultivated pak choi in treatments amended
      with the same amount of Se-enriched wheat straw and pak choi were 1.7 and 9.7
      times in the shoots and 2.3 and 6.3 times in the roots compared with control
      treatment. Soil respiration rate was significantly increased after all organic
      material amendment in soil (p < 0.05), which accelerated the mineralization of
      organic materials and thus resulted in soluble Se (SOL-Se), exchangeable Se (EX
      Se), and fulvic acid-bound Se (FA-Se) fraction increasing by 25.2-29.2%, 9-13.8%,
      and 4.92-8.28%, respectively. In addition, both Pearson correlation and cluster
      analysis showed that EX-Se and FA-Se were better indicators for soil Se
      availability in organic material amendment soils. The Marquardt-Levenberg Model
      well described the dynamic kinetics of FA-Se content after Se-enriched organic
      material amendment in soil mainly because of the mineralization of organic carbon
      and organo-selenium. The utilization of Se in P + Se treatment was significantly
      higher than those in WS + Se treatment because of the different mineralization
      rates and the amount of FA-Se in soil. Se-enriched organic materials amendment
      can not only increase the availability of selenium in soil but also avoid the
      waste of valuable Se source.

PMID- 29453069
TI  - Combined effect of copper and hydrodynamic conditions on Myriophyllum
      alterniflorum biomarkers.
AB  - The aim of this study is to determine the combined effect of copper and
      hydrodynamic conditions on the response of certain biomarkers of an aquatic
      macrophyte, namely Myriophyllum alterniflorum. Watermilfoil biomarkers are
      monitored in a synthetic medium enriched or not with copper (100 MUg.L-1) for 21
      days in aquarium systems (150 L), under three hydrodynamic conditions: laminar,
      turbulent, and calm. The studied biomarkers are: respiratory and photosynthetic
      activities; concentrations of chlorophyll a, b and carotenoids; osmotic
      potential; hydrogen peroxide content; and growth. In addition, Cu contents in
      water and in Myriophyllum alterniflorum (roots and shoots) are investigated. The
      hydrodynamic conditions only affect watermilfoil morphology. Copper accumulates
      less in turbulent zones; moreover, it is more likely to accumulate in shoots than
      in roots, except within the calm zone. Cu leads to: i) a significant increase in
      H2O2 content, ii) a decrease in root growth, pigment content, osmotic potential,
      photosynthesis and respiration rates, and iii) an inhibition of shoot branching.
      Differential effects are also observed between younger and older parts, thus
      indicating the benefit of considering these two plant parts separately in water
      quality biomonitoring.

PMID- 29453070
TI  - Magnetic Zr-MOFs nanocomposites for rapid removal of heavy metal ions and dyes
      from water.
AB  - Amino-decorated Zr-based magnetic Metal-Organic Frameworks composites (Zr-MFCs)
      were prepared by a facile and efficient strategy. The nano-sized Fe3O4@SiO2 core
      (about 15 nm) was coated with a shell of Zr-MOFs (about 5 nm) by means of in-situ
      growth. And, Fe3O4@SiO2@UiO-66 and its amino derivatives (Fe3O4@SiO2@UiO-66-NH2
      and Fe3O4@SiO2@UiO-66-Urea) were successfully prepared by using different
      precursors. The obtained Zr-MFCs were demonstrated to be efficient adsorbents for
      metal ions/organic dyes removal from aqueous solution, with high adsorption
      capacity and fast adsorption kinetics. It was found that the amine-decorated MFCs
      were highly efficient for metal ions/dyes removal compared to raw MFC-O. Among
      them, MFC-N exhibited the highest capacity for Pb2+ (102 mg g-1) and methylene
      blue (128 mg g-1), while MFC-O exhibited the highest capacity for methyl orange
      (219 mg g-1). Moreover, anionic and cationic dyes could be selectively separated
      and removed from the mixed solution just by adjusting the solution pH with Zr
      MFCs as the adsorbents. And these Zr-MFCs materials can be easily regenerated by
      desorbing metal ions/organic dyes from the sorbents with appropriate eluents, and
      the adsorption capacity can be remained unchanged after 6 recycles. The obtained
      results demonstrated the great application potential of the prepared MFCs as
      fascinating adsorbents for water treatment.

PMID- 29453071
TI  - Degradation of dye Procion Red MX-5B by electrolytic and electro-irradiated
      technologies using diamond electrodes.
AB  - This work focuses on the treatment of synthetic wastewater polluted with dye
      Procion Red MX-5B by different Electrochemical Advanced Oxidation Processes
      (EAOP) based on diamond anodes. The influence of the current density and the
      supporting electrolyte has been studied on dye removal and total mineralization
      of the organic matter. Results show that electrolysis with diamond electrodes is
      a suitable technology for an efficient degradation of dye. Nonetheless, the
      process efficiency increases when using chloride as supporting electrolyte
      because of the electrochemical generation of hypochlorite in wastewater which
      significantly contribute to dye removal. On the contrary, the total
      mineralization of the organic matter is more efficient in sulfate media. In this
      case, large amounts of peroxodisulfate are electrogenerated, favoring the
      complete removal of total organic carbon (TOC). On the other hand, lower current
      densities (10 mA cm-2) lead to a more efficient removal of both dye and TOC due
      to the mass transfer limitations of the technology. Finally, the coupling of UV
      light irradiation or ultrasound to electrolysis significantly improves the
      process performance, being photoelectrolysis the most efficient technology for
      the treatment of wastewater polluted with Procion Red MX-5B. This fact is due to
      the potential production of free chlorine or sulfate radicals that takes place by
      the activation of the electrogenerated oxidants. These species are more reactive
      than oxidants and, therefore, they quickly attack the organic matter present in
      wastewater.

PMID- 29453072
TI  - Selection criteria for oxidation method in total organic carbon measurement.
AB  - During the measurement of total organic carbon (TOC), dissolved organic carbon is
      converted into CO2 by using high temperature combustion (HTC) or wet chemical
      oxidation (WCO). However, the criteria for selecting the oxidation methods are
      not clear. In this study, the chemical structures of organic material were
      considered as a key factor to select the oxidation method used. Most non
      degradable organic compounds showed a similar oxidation efficiency in both
      methods, including natural organic compounds, dyes, and pharmaceuticals, and thus
      both methods are appropriate to measure TOC in waters containing these compounds.
      However, only a fraction of the carbon in the halogenated compounds
      (perfluorooctanoic acid and trifluoroacetic acid) were oxidized using WCO,
      resulting in measured TOC values that are considerably lower than those
      determined by HTC. This result is likely due to the electronegativity of halogen
      elements which inhibits the approach of electron-rich sulfate radicals in the
      WCO, and the higher bond strength of carbon-halogen pairs as compared to carbon
      hydrogen bonds, which results in a lower degree of oxidation of the compounds.
      Our results indicate that WCO could be used to oxidize most organic compounds,
      but may not be appropriate to quantify TOC in organic carbon pools that contain
      certain halogenated compounds.

PMID- 29453073
TI  - Stabilization of lead (Pb) and zinc (Zn) in contaminated rice paddy soil using
      starfish: A preliminary study.
AB  - Lead (Pb) and zinc (Zn) contaminated rice paddy soil was stabilized using natural
      (NSF) and calcined starfish (CSF). Contaminated soil was treated with NSF in the
      range of 0-10 wt% and CSF in the range of 0-5 wt% and cured for 28 days. Toxicity
      characteristic leaching procedure (TCLP) test was used to evaluate effectiveness
      of starfish treatment. Scanning electron microscopy-energy dispersive X-ray
      spectroscopy (SEM-EDX) analyses were conducted to investigate the mechanism
      responsible for effective immobilization of Pb and Zn. Experimental results
      suggest that NSF and CSF treatments effectively immobilize Pb and Zn in treated
      rice paddy soil. TCLP levels for Pb and Zn were reduced with increasing NSF and
      CSF dosage. Comparison of the two treatment methods reveals that CSF treatment is
      more effective than NSF treatment. Leachability of the two metals is reduced
      approximately 58% for Pb and 51% for Zn, upon 10 wt% NSF treatment. More
      pronounced leachability reductions, 93% for Pb and 76% for Zn, are achieved upon
      treatment with 5 wt% CSF. Sequential extraction results reveal that NSF and CSF
      treatments of contaminated soil generated decrease in exchangeable/weak acid Pb
      and Zn soluble fractions, and increase of residual Pb and Zn fractions. Results
      for the SEM-EDX sample treated with 5 wt% CSF indicate that effective Pb and Zn
      immobilization is most probably associated with calcium silicate hydrates (CSHs)
      and calcium aluminum hydrates (CAHs).

PMID- 29453074
TI  - Use of prostaglandin F2alpha as ovulatory stimulus for synchronizing dairy
      cattle.
AB  - The aim of this study was to evaluate if prostaglandin F2alpha (PGF) can be used
      to induce ovulation in a GnRH-progesterone based protocol. In Experiment 1
      crossbred dairy cows (n=32) were synchronized with a progesterone-GnRH based
      protocol for seven days, where the luteolytic dose of 150MUg PGF was given 24h
      prior progesterone device removal (CIDR). On Day 8 cows were separated into two
      groups to receive: 1) 2mL of Saline (Control Group, n=15) or 2) 150MUg of PGF
      (PGF Group, n=17). Ovulation rate was higher in the PGF than Control group (100%
      vs 53.3%, P=0.001, Odds ratio=30.88). The percentage of cows that ovulated
      synchronously tended to be higher in the PGF than Control group (P=0.1, Odds
      ratio=9.6). Experiment 2 was performed in a cross-over (3*3) design. Crossbred
      dairy cows (n=25) received a CIDR for seven days and GnRH on Day 0. Seven days
      later 150MUg of PGF was given and the progesterone device was removed, and 24h
      later cows were distributed into three groups to receive: 1) 2mL of Saline
      (Control Group, n=25), 2) 150MUg of PGF (PGF Group, n=25) or 3) 1mg of ECP (ECP
      Group, n=23). Diameter of ovulatory follicle was larger in the PGF and Control
      than ECP Group (P=0.002, Effect size>4.0). Synchronized ovulation rate (between
      72 and 96h after CIDR removal) tended to be higher in PGF group in Control group
      (P=0.1, Odds ratio=0.35). Results suggest that PGF is equally efficient to ECP to
      induce synchronized ovulation in dairy cows subjected to progesterone-GnRH based
      protocols.

PMID- 29453075
TI  - Pharmacokinetic variability of valproate during pregnancy - Implications for the
      use of therapeutic drug monitoring.
AB  - BACKGROUND AND PURPOSE: Use of valproate (VPA) in women of childbearing age is
      restricted due to dose-dependent risk of teratogenicity. The purpose of this
      study was to characterise pharmacokinetic variability of VPA in pregnancy, and
      discuss use of therapeutic drug monitoring (TDM) as guidance to exposure in
      women. METHOD: Measurements of trough total and unbound VPA concentrations
      before, during and after pregnancy, at assumed steady-state were collected from
      the TDM-database (2006-2016) at the National Center for Epilepsy in Norway.
      Additional clinical data were obtained from the Oppland county Perinatal Database
      (1994-2011). RESULTS: Data from 51 pregnancies in 33 women aged 19-40 years were
      included. Each woman underwent 1-4 pregnancies, and 1-7 measurements per
      pregnancy were performed. The variability in total concentration/dose (C/D)
      ratios between women was 13-fold, and intra-patient variability extensive. Total
      C/D-ratios were reduced by 46% from before pregnancy to third trimester (0.48
      0.29 MUmol/L/mg). Unbound concentrations of VPA were only requested in 10% of the
      pregnancies. Repeated measurements from two pregnancies in one women revealed
      increased unbound concentration of VPA during pregnancy. There were 19 with
      idiopathic generalized epilepsy and two focal based on clinical data from 21
      women and 38 pregnancies; 1 major congenital malformation was noted. CONCLUSION:
      There is pronounced pharmacokinetic variability of VPA during pregnancy. Unbound
      concentrations are rarely requested. TDM should be used by measurements of both
      total and unbound concentrations since total concentrations may be misleading for
      efficacy and fetal exposure of VPA.

PMID- 29453076
TI  - Development of novel synthesized phthalazinone-based PARP-1 inhibitors with
      apoptosis inducing mechanism in lung cancer.
AB  - Herein we report the synthesis of two series of 4-phenylphthalazin-1-ones 11a-i
      and 4- benzylphthalazin-1-ones 16a-h as anti-lung adenocarcinoma agents with
      potential inhibitory activity against PARP-1. All the newly synthesized
      phthalazinones were evaluated for their anti-proliferative activity against A549
      lung carcinoma cell line. Phthalazinones 11c-i and 16b, c showed significant
      cytotoxic activity against A549 cells at different concentrations (0.1, 1 and 10
      MUM) for two time intervals (24 h and 48 h). These nine phthalazinones were
      further examined for their inhibitory activity towards PARP-1. Compound 11c
      emerged as the most potent PARP-1 inhibitor with IC50 value of 97 nM, compared to
      that of Olaparib (IC50 = 139 nM). Furthermore, all these nine phthalazinones
      passed the filters of Lipinski and Veber rules, and predicted to have good
      pharmacokinetics properties in a theoretical kinetic study. On the other hand,
      western blotting in A549 cells revealed the enhanced expression of the cleaved
      PARP-1, alongside, with the reduced expression of pro-caspase-3 and
      phosphorylated AKT. In addition, ELISA assay confirmed the up-regulation of
      active caspase-3 and caspase-9 levels compared to the control, suggesting the
      activation of the apoptotic machinery in the A549 cells. Finally, molecular
      docking of 11c into PARP-1 active site (PDB: 5WRZ) was performed to explore the
      probable binding mode.

PMID- 29453077
TI  - Molecular docking simulation, synthesis and 3D pharmacophore studies of novel 2
      substituted-5-nitro-benzimidazole derivatives as anticancer agents targeting
      VEGFR-2 and c-Met.

PMID- 29453078
TI  - Diterpenoids from the roots of Euphorbia ebracteolata and their anti-tuberculosis
      effects.
AB  - Euphorbia ebracteolata was a natural medicine for the treatment of tuberculosis.
      The present work has performed the investigation of bioactive chemical substances
      from the roots of E. ebracteolata. Using various chromatographic techniques, 15
      compounds were obtained from the roots of E. ebracteolata. On the basis of widely
      spectroscopic data analyses, the isolated compounds were determined to be
      diterpenoids, including rosane derivatives (1-12), isopimarane (13), abietane
      (14), and lathyrane (15), among which compounds 1-4, and 9 were undescribed
      previously. The inhibitory effects of isolated diterpenoids against Mycobacterium
      tuberculosis were evaluated using an Alamar blue cell viability assay. And two
      rosane-type diterpenoids 3 and 8 displayed moderate inhibitory effects on with
      the MIC values of 18 MUg/mL and 25 MUg/mL, respectively. For the potential
      inhibitor 3, the inhibitory effect against the target enzyme GlmU was evaluated,
      which displayed a moderate inhibitory effect with the IC50 12.5 MUg/mL.
      Therefore, the diterpenoids from the roots of E. ebracteolata displayed anti
      tuberculosis effects, which would be pay more attentions for the anti
      tuberculosis agents.

PMID- 29453079
TI  - Spectral/target activity of short lived radio isotope in pulsed plasma
      accelerator.
AB  - Accelerated deuteron spectra from magnetic spectrometry and graphite bombardment
      by such deuterons were used to produce short-lived radionuclides in NX2 plasma
      focus. The experiments show one order of magnitude difference between the
      activity generated by these techniques. The average activity of NX2 is 5.2 kBq
      and the highest activity for the best shot is about 40 kBq.

PMID- 29453080
TI  - Improvement of the radiographic method for measurement of effective energy of
      pulsed X-ray emission from a PF device for different anode's insert materials.
AB  - In this paper, effective energy of pulsed X-Ray emitted from a Mather-type plasma
      focus device in stored energy of 2.5 kJ with six different anode's insert
      materials was measured using radiographic method with attenuation filters. Since
      intensity and energy of X-ray beam were considerably changed with changing the
      insert material, the method was improved by using different filters
      simultaneously in all the experiments and selection of the best filter in each
      experiment according to the appropriate criteria. Effective energy of pulsed X
      ray beam was measured 16, 28, 50, 51, 34 and 44 keV when aluminum, copper, zinc,
      tin, tungsten and lead were used as insert materials, and aluminum, copper,
      silver, silver, copper and lead were used as filters, respectively.

PMID- 29453081
TI  - Sluggish dorsally-driven inhibition of return during orthographic processing in
      adults with dyslexia.
AB  - Dyslexia (D) is a neurodevelopmental reading disorder characterized by
      phonological and orthographic deficits. Before phonological decoding, reading
      requires a specialized orthographic system for parallel letter processing that
      assigns letter identities to different spatial locations. The magnocellular
      dorsal (MD) stream rapidly process the spatial location of visual stimuli
      controlling visuo-spatial attention. To investigate the visuo-spatial attention
      efficiency during orthographic processing, inhibition of return (IOR) was
      measured in adults with and without D in a lexical decision task. IOR is the
      delay in responding to stimuli displayed in a cued location after a long cue
      target interval. Only adults with D did not showed IOR effect during letter
      string recognition, despite the typical left-hemisphere specialization for word
      identification. A specific deficit in coherent-dot-motion perception confirmed an
      MD-stream disorder in adults with D. Our results suggest that adults with D might
      develop an efficient visual word form area, but a dorsal-attentional dysfunction
      impairs their reading fluency.

PMID- 29453082
TI  - Potential roles for transposable elements in creating imprinted expression.
AB  - Changes in gene expression can have profound effects on phenotype. Nature has
      provided many complex patterns of gene regulation such as imprinting. Imprinted
      genes exhibit differences in the expression of the maternal and paternal alleles,
      even though they reside in the same nucleus with access to the same trans-acting
      factors. Significant attention has been focused on the potential reasons that
      imprinted expression could be beneficial and stabilized by selection. However,
      less attention has focused on understanding how imprinted expression might arise
      or decay. We discuss the evidence for frequent turnover of imprinted expression
      based on evolutionary analyses in plants and the potential role for transposable
      elements (TEs) in creating imprinted expression patterns.

PMID- 29453083
TI  - Nonuniform sampling by quantiles.
AB  - A flexible strategy for choosing samples nonuniformly from a Nyquist grid using
      the concept of statistical quantiles is presented for broad classes of NMR
      experimentation. Quantile-directed scheduling is intuitive and flexible for any
      weighting function, promotes reproducibility and seed independence, and is
      generalizable to multiple dimensions. In brief, weighting functions are divided
      into regions of equal probability, which define the samples to be acquired.
      Quantile scheduling therefore achieves close adherence to a probability
      distribution function, thereby minimizing gaps for any given degree of
      subsampling of the Nyquist grid. A characteristic of quantile scheduling is that
      one-dimensional, weighted NUS schedules are deterministic, however higher
      dimensional schedules are similar within a user-specified jittering parameter. To
      develop unweighted sampling, we investigated the minimum jitter needed to disrupt
      subharmonic tracts, and show that this criterion can be met in many cases by
      jittering within 25-50% of the subharmonic gap. For nD-NUS, three supplemental
      components to choosing samples by quantiles are proposed in this work: (i)
      forcing the corner samples to ensure sampling to specified maximum values in
      indirect evolution times, (ii) providing an option to triangular backfill
      sampling schedules to promote dense/uniform tracts at the beginning of signal
      evolution periods, and (iii) providing an option to force the edges of nD-NUS
      schedules to be identical to the 1D quantiles. Quantile-directed scheduling meets
      the diverse needs of current NUS experimentation, but can also be used for future
      NUS implementations such as off-grid NUS and more. A computer program
      implementing these principles (a.k.a. QSched) in 1D- and 2D-NUS is available
      under the general public license.

PMID- 29453084
TI  - Solid lipid nanoparticles as an efficient drug delivery system of olmesartan
      medoxomil for the treatment of hypertension.
AB  - The aim of the current investigation was to develop solid lipid nanoparticles of
      olmesartan medoxomil using hot homogenization method to improve its oral
      bioavailability. Central composite design was applied to optimize the formulation
      variables; lipid X1 (Glyceryl monostearate) and surfactant X2 (Poloxamer: Tween
      80). The particle sizes were in the nanometer range and spherical shaped for all
      prepared solid lipid nanoparticles formulations and the zeta potential absolute
      values were high, predicting good long-term stability. In vitro study of
      olmesartan loaded solid lipid nanoparticle exhibited controlled release profile
      for at least 24 h. The rate and extent of drug diffusion was studied using
      dialysis sac, rat's stomach and intestine tissues; study demonstrated that drug
      release from the solid lipid nanoparticles was significantly higher than drug
      suspension. In vivo pharmacokinetic study of olmesartan loaded solid lipid
      nanoparticles revealed higher Cmax of 1610 ng/mL, higher AUC of 15492.50 ng/mL
      and increased relative bioavailability by almost 2.3 folds compared to marketed
      formulation. These results clearly indicate that olmesartan loaded solid lipid
      nanoparticles are shown to have enhanced bioavailability and effective
      therapeutic result and thus would be an excellent way to treat hypertension.
      Hence, these solid lipid nanoparticles could represent as a great potential for a
      possible alternative to conventional oral formulation in the treatment of
      hypertension.

PMID- 29453085
TI  - The effect of the molecular weight of hyaluronic acid on the physicochemical
      characterization of hyaluronic acid-curcumin conjugates and in vitro evaluation
      in glioma cells.
AB  - In this study, a redox-sensitive glioma-targeting micelle system was designed to
      deliver curcumin (CUR) by conjugating it to hyaluronic acid (HA-s-s-CUR, HSC) via
      disulfide linkage. The effect of the molecular weight of HA on the
      physicochemical characteristics of HSC conjugates and their in vitro effects in
      glioma cells were also explored. These conjugates formed nano-scale micelles (209
      926 nm) independently in aqueous solution. The micelles greatly increased the
      solubility of CUR and improved its stability, which is crucial for harnessing the
      therapeutic potential of this active molecule. The redox sensitivities of
      different HSC micelles were measured by using a dynamic light scattering method
      and in vitro release assay, which showed that the low (50 kDa) and medium
      molecular weight (200 kDa and 500 kD) HA-based conjugates were sensitive to GSH,
      whereas higher molecular weights (1000 kDa and 2000 kDa) did not show redox
      sensitivity. Increased cytotoxicity and uptake of low and medium molecular weight
      modified HSC conjugates by the glioma cells further confirmed that the sensitive
      micelles are more effective for intracellular drug delivery compared to the high
      molecular weight-modified HSC conjugates or the plain CUR. In summary, the
      molecular weight of HA affects the physicochemical attributes of HSC conjugates.
      Only HSC micelles made with HA molecules less than 500 kDa exhibit redox
      sensitivity.

PMID- 29453086
TI  - PEGylated polyaminoacid-capped mesoporous silica nanoparticles for mitochondria
      targeted delivery of celastrol in solid tumors.
AB  - The major goal of cancer chemotherapy is to maximize the therapeutic efficacy of
      anticancer drugs, while minimizing their associated side effects. Celastrol
      (CST), which is extracted from the traditional Chinese medicinal plant
      Tripterygium wilfordii, has been reported to exhibit significant anticancer
      effects in various in vitro and in vivo cancer models. Nanoparticulate drug
      delivery systems could be employed to preserve and enhance the pharmacological
      effects of CST in cancer cells. Among these, mesoporous silica nanoparticles
      (MSNs) are one of the most promising drug delivery systems. MSNs possess the
      capability of passive accumulation within solid tumors, and could efficiently
      transport anticancer drugs to such tumors in a site-specific manner. In this
      study, PEGylated polyaminoacid-capped CST-loaded MSN (CMSN-PEG) showed controlled
      in vitro drug release behavior, and exhibited high in vitro cytotoxicity in
      different cancer cells. Compared to treatment with free CST, treatment with CMSN
      PEG resulted in the increased expression of the apoptosis protein HIF-1alpha and
      proteins corresponding to mitochondrial apoptosis pathway. Importantly, CMSN-PEG
      remarkably reduced tumor burden with no toxicity to healthy cells in the SCC7
      tumor-bearing xenograft model. Our results clearly demonstrate a promising
      potential of CMSN-PEG for the treatment of solid tumors.

PMID- 29453087
TI  - Interleukin-6 is an independent predictor of progressive atherosclerosis in the
      carotid artery: The Tromso Study.
AB  - BACKGROUND AND AIMS: Novel biomarkers are linked to cardiovascular disease (CVD).
      The aim of the present study was to investigate the association between 28 blood
      biomarkers and the formation and progression of carotid plaque. METHODS: In a
      nested case control study with 703 participants from the population based Tromso
      Study, a large biomarker panel was measured in blood obtained at baseline.
      Carotid ultrasound was assessed both at baseline and at 6 years of follow-up.
      Four groups were defined: Group 1: no plaque at baseline or at follow-up
      (reference group); Group 2: novel plaque at follow-up; Group 3: stable plaque at
      follow-up; Group 4: progression of plaque at follow-up. By multinomial logistic
      regression analyses, we assessed the risk of being in the different plaque groups
      with regard to traditional cardiovascular risk factors and levels of biomarkers
      at baseline. RESULTS: Adjusted for traditional risk factors, interleukin-6 (IL-6)
      was an independent predictor of plaque progression (OR 1.44, 95% CI 1.12-1.85 per
      SD increase in IL-6 level). This result remained significant after inclusion of
      other novel biomarkers to the model, and when subjects with former CVD were
      excluded. Neopterin was protective of novel plaque formation (OR 0.73, 95% CI
      0.57-0.93). Myeloperoxidase and Caspase-1 were independent predictors of plaque
      progression, but this effect disappeared when excluding subjects with former CVD.
      CONCLUSIONS: IL-6 is an independent predictor of plaque progression, suggesting
      that it may be a marker of progressive atherosclerosis in the general population
      and that its central role in CVD may be related to promotion of plaque growth.

PMID- 29453088
TI  - Serum matrix metalloproteinase-8, tissue inhibitor of metalloproteinase and
      myeloperoxidase in ischemic stroke.
AB  - BACKGROUND AND AIMS: Matrix metalloproteinase (MMP)-8 and myeloperoxidase (MPO)
      may contribute to cerebral damage in acute ischemic stroke. We tested the
      hypothesis that levels of MPO, MMP-8 and the ratio between MMP-8 and its
      regulator, tissue inhibitor of metalloproteinase (TIMP-1), are increased in acute
      ischemic stroke and its etiologic subgroups and they correlate with stroke
      severity. METHODS: In a cross-sectional case-control study, serum concentrations
      of MMP-8, MPO and TIMP-1 were assessed within 24 h after admission in 470 first
      ever ischemic stroke patients and 809 age- and sex-matched controls, randomly
      selected from the population. Odds ratios (OR) per decade of log transformed
      dependent variables were calculated and adjusted for age, sex and vascular risk
      factors. RESULTS: Levels of MMP-8 (OR 4.9; 95% CI 3.4-7.2), MMP-8/TIMP-1 ratio
      (3.0; 2.2-4.1) and MPO (6.6; 4.0-11.0) were independently associated with
      ischemic stroke. MMP-8 levels differed between etiologic stroke subgroups (p =
      0.019, ANOVA), with higher levels in cardioembolic stroke and stroke due to large
      vessel disease, and lower levels in microangiopathic stroke. MMP-8, MMP-8/TIMP-1
      ratio and MPO (p < 0.001) concentrations showed positive associations with stroke
      severity independent of stroke etiology. CONCLUSIONS: Concentrations of serum
      neutrophil markers are increased after ischemic stroke and associate with stroke
      severity and etiology. The value of these biomarkers in diagnostics and
      prognostics is worth being evaluated.

PMID- 29453089
TI  - Botanical essential oils and uses as mosquitocides and repellents against dengue.
AB  - Plants naturally produce bioactive compounds along with many secondary
      metabolites which serve as defensive chemical against herbivorers including
      insect pests. One group of these phytochemicals are the 'Essential Oils' (EO's),
      which possess an extensive range of biological activity especially insecticidal
      and insect repellents. This review provides a comprehensive viewpoint on
      potential modes of action of biosafety plant derived Essential Oils (EO's) along
      with their principal chemical derivatives against larvae and adult mosquito
      vectors of dengue virus. The development and use of Essential Oils (EO's)
      effectively applied in small rural communities provides an enormous potential for
      low cost effective management of insect vectors of human pathogens which cause
      disease.

PMID- 29453090
TI  - Evaluating effects of prenatal exposure to phthalate mixtures on birth weight: A
      comparison of three statistical approaches.
AB  - OBJECTIVES: We applied three statistical approaches for evaluating associations
      between prenatal urinary concentrations of a mixture of phthalate metabolites and
      birth weight. METHODS: We included 300 women who provided 732 urine samples
      during pregnancy and delivered a singleton infant. We measured urinary
      concentrations of metabolites of di(2-ethylhexyl)-phthalate, di-isobutyl-, di-n
      butyl-, butylbenzyl-, and diethyl phthalates. We applied 1) linear regressions;
      2) classification methods [principal component analysis (PCA) and structural
      equation models (SEM)]; and 3) Bayesian kernel machine regression (BKMR), to
      evaluate associations between phthalate metabolite mixtures and birth weight
      adjusting for potential confounders. Data were presented as mean differences (95%
      CI) in birth weight (grams) as each phthalate increased from the 10th to the 90th
      percentile. RESULTS: When analyzing individual phthalate metabolites using linear
      regressions, each metabolite demonstrated a modest inverse association with birth
      weight [from -93 (-206, 21) to -49 (-164, 65)]. When simultaneously including all
      metabolites in a multivariable model, inflation of the estimates and standard
      errors were noted. PCA identified two principal components, both inversely
      associated with birth weight [-23 (-68, 22), -27 (-71, 17), respectively]. These
      inverse associations were confirmed when applying SEM. BKMR further identified
      that monoethyl and mono(2-ethylhexyl) phthalate and phthalate concentrations were
      linearly related to lower birth weight [-51(-164, 63) and -122 (-311, 67),
      respectively], and suggested no evidence of interaction between metabolites.
      CONCLUSIONS: While none of the methods produced significant results, we
      demonstrated the potential issues arising using linear regression models in the
      context of correlated exposures. Among the other selected approaches,
      classification techniques identified common sources of exposures with
      implications for interventions, while BKMR further identified specific
      contributions of individual metabolites.

PMID- 29453091
TI  - Identification of miRNAs and their targets in maize in response to Sugarcane
      mosaic virus infection.
AB  - MicroRNAs (miRNAs) are endogenous non-coding small RNAs that play essential
      regulatory roles in plant development and environmental stress responses. Maize
      (Zea mays L.) is a global economically important food and forage crop. To date, a
      number of maize miRNAs have been identified as being involved in plant
      development and stress responses. However, the miRNA-mediated gene regulatory
      networks responsive to virus infections in maize remain largely unknown. In this
      study, the profiles of small RNAs in buffer- and Sugarcane mosaic virus (SCMV)
      inoculated maize plants were obtained by high-throughput sequencing,
      respectively. A total of 154 known miRNAs and 213 novel miRNAs were profiled and
      most of the miRNAs identified were differentially expressed after SCMV infection.
      In addition, 70 targets of 13 known miRNAs and 3 targets of a novel miRNA were
      identified by degradome analysis. The results of Northern blotting and
      quantitative real-time PCR showed that the expression levels of the selected
      miRNAs and their targets were mostly influenced by SCMV infection at 12 days post
      inoculation, including up-regulation of miR168 and miR528, and down-regulation of
      miR159, miR397 and miR827. These results provide new insights into the regulatory
      networks of miRNAs and their targets in maize plants responsive to SCMV
      infection.

PMID- 29453092
TI  - Silicon induced Fe deficiency affects Fe, Mn, Cu and Zn distribution in rice
      (Oryza sativa L.) growth in calcareous conditions.
AB  - A protective effect by silicon in the amelioration of iron chlorosis has recently
      been proved for Strategy 1 species, at acidic pH. However in calcareous
      conditions, the Si effect on Fe acquisition and distribution is still unknown. In
      this work, the effect of Si on Fe, Mn, Cu and Zn distribution was studied in rice
      (Strategy 2 species) under Fe sufficiency and deficiency. Plants (+Si or-Si) were
      grown initially with Fe, and then Fe was removed from the nutrient solution. The
      plants were then analysed using a combined approach including LA-ICP-MS images
      for each element of interest, the analysis of the Fe and Si concentration at
      different cell layers of root and leaf cross sections by SEM-EDX, and determining
      the apoplastic Fe, total micronutrient concentration and oxidative stress
      indexes. A different Si effect was observed depending on plant Fe status. Under
      Fe sufficiency, Si supply increased Fe root plaque formation, decreasing Fe
      concentration inside the root and increasing the oxidative stress in the plants.
      Therefore, Fe acquisition strategies were activated, and Fe translocation rate to
      the aerial parts was increased, even under an optimal Fe supply. Under Fe
      deficiency, +Si plants absorbed Fe from the plaque more rapidly than -Si plants,
      due to the previous activation of Fe deficiency strategies during the growing
      period (+Fe + Si). Higher Fe plaque formation due to Si supply during the growing
      period reduced Fe uptake and could activate Fe deficiency strategies in rice,
      making it more efficient against Fe chlorosis alterations. Silicon influenced Mn
      and Cu distribution in root.

PMID- 29453093
TI  - Instruments for evaluation of safety culture in primary health care: integrative
      review of the literature.
AB  - OBJECTIVES: This research aimed to conduct an investigation of the tools used to
      assess safety culture in the primary health care. STUDY DESIGN: Integrative
      review of the literature. METHODS: We conducted a literature search using an
      instrument that included quantitative assessments of safety culture, using the
      following databases: CINAHL, ScienceDirect, PubMed, BIREME, and SciELO. Retrieved
      material comprised original articles published from 1998 to 2014, with titles and
      abstracts available in English, Portuguese, Spanish, and French. RESULTS: The
      search resulted in seven instruments; however, only three were primary healthcare
      focused. CONCLUSION: Most of the existing instruments for assessing safety
      culture have acceptable psychometric properties. The study serves as a source for
      students, workers, and researchers who want to know more about appropriate
      instruments for evaluating safety culture in primary care.

PMID- 29453094
TI  - A multidisciplinary study of 3-(beta-d-glucopyranosyl)-5-substituted-1,2,4
      triazole derivatives as glycogen phosphorylase inhibitors: Computation,
      synthesis, crystallography and kinetics reveal new potent inhibitors.
AB  - 3-(beta-d-Glucopyranosyl)-5-substituted-1,2,4-triazoles have been revealed as an
      effective scaffold for the development of potent glycogen phosphorylase (GP)
      inhibitors but with the potency very sensitive to the nature of the alkyl/aryl 5
      substituent (Kun et al., Eur. J. Med. Chem. 2014, 76, 567). For a training set of
      these ligands, quantum mechanics-polarized ligand docking (QM-PLD) demonstrated
      good potential to identify larger differences in potencies (predictive index PI =
      0.82) and potent inhibitors with Ki's < 10 MUM (AU-ROC = 0.86). Accordingly, in
      silico screening of 2335 new analogues exploiting the ZINC docking database was
      performed and nine predicted candidates selected for synthesis. The compounds
      were prepared in O-perbenzoylated forms by either ring transformation of 5-beta-d
      glucopyranosyl tetrazole by N-benzyl-arenecarboximidoyl chlorides, ring closure
      of C-(beta-d-glucopyranosyl)formamidrazone with aroyl chlorides, or that of N
      (beta-d-glucopyranosylcarbonyl)arenethiocarboxamides by hydrazine, followed by
      deprotections. Kinetics experiments against rabbit muscle GPb (rmGPb) and human
      liver GPa (hlGPa) revealed five compounds as potent low MUM inhibitors with three
      of these on the submicromolar range for rmGPa. X-ray crystallographic analysis
      sourced the potency to a combination of favorable interactions from the 1,2,4
      triazole and suitable aryl substituents in the GP catalytic site. The compounds
      also revealed promising calculated pharmacokinetic profiles.

PMID- 29453095
TI  - Simultaneous measurement of contents of liquirtin and glycyrrhizic acid in
      liquorice based on near infrared spectroscopy.
AB  - OBJECTIVE: To establish calibration models for simultaneous determination of
      contents of liquirtin and glycyrrhizic acid, and to investigate the variable
      selection methods. METHODS: The contents of liquirtin and glycyrrhizic acid
      determined by HPLC were as the reference values, which were associated with
      samples spectra by using near infrared spectrum (NIR) analysis technology.
      Calibration models were developed using partial least squares (PLS) regression
      algorithm, and evaluated by the independent dataset test with calculating the
      metrics of coefficients of determination of calibration and prediction (R2c,
      R2p), the root mean square errors of calibration and prediction (RMSEC, RMSEP),
      the mean absolute errors of calibration and prediction (MAEC, MAEP), and the
      residual prediction deviation (RPD). Five variable selection methods including
      variable importance in projection (VIP), competitive adaptive reweighted sampling
      (CARS), Monte Carlo uninformative variable elimination (MCUVE), particle swarm
      optimization (PSO) and genetic algorithm (GA), were investigated. RESULTS:
      Compared to the original full spectra, both quantification models for liquirtin
      and glycyrrhizic acid performed better with a clear ranking of
      GA>PSO>CARS>MCUVE?VIP>Full. Especially for GA-PLS models, RMSEC and RMSEP were
      <0.05%, R2c and R2p were >0.94, and RPD were both >4, indicating that both the
      models had good robustness and excellent prediction accuracy. CONCLUSION: The
      present calibration models can be utilized to simultaneously determine the
      contents of liquirtin and glycyrrhizic acid in liquorice samples, and thus are of
      great help for rapid quality evaluation and control of liquorice.

PMID- 29453096
TI  - Design of mitochondria-targeted colorimetric and ratiometric fluorescent probes
      for rapid detection of SO2 derivatives in living cells.
AB  - Two mitochondria-targeted colorimetric and ratiometric fluorescent probes for SO2
      derivatives were constructed based on the SO2 derivatives-triggered Michael
      addition reaction. The probes exhibit high specificity toward HSO3-/SO32- by
      interrupting their conjugation system resulting in a large ratiometric blue shift
      of 46-121nm in their emission spectrum. The two well-resolved emission bands can
      ensure accurate detection of HSO3-. The detection limits were calculated to be
      1.09 and 1.35MUM. Importantly, probe 1 and probe 2 were successfully used to
      fluorescence ratiometric imaging of endogenous HSO3- in BT-474 cells.

PMID- 29453097
TI  - Self-assembled vertically aligned Au nanorod arrays for surface-enhanced Raman
      scattering (SERS) detection of Cannabinol.
AB  - Self-assembled multi-layered vertically aligned gold nanorod (AuNR) arrays have
      been fabricated by a simple preparation process that requires a balance between
      the particle concentration and the ionic strength of the solvent. An
      experimentally determined critical AuNR concentration of 2.0nM and 50mM NaCl
      produces well-ordered vertically aligned hexagonally close-packed AuNR arrays. We
      demonstrate surface treatment via UV Ozone cleaning of such samples to allow
      introduction of analyte molecules (benzenethiol and cannabinol) for effective
      surface enhanced Raman scattering detection. This is the first demonstration of
      the SERS analysis of cannabinol. This approach demonstrates a cost-effective,
      high-yield and simple fabrication route to SERS sensors with application in the
      screening for the cannabinoids.

PMID- 29453098
TI  - Control of viral transcripts as a concept for future HBV therapies.
AB  - Chronic hepatitis B virus infections affect over 250 million people world-wide,
      and, at present, are not curable. Of those, over 800000 are expected to die
      yearly from complications including cirrhosis and primary hepatocellular
      carcinoma (HCC). A viral episomal DNA intermediate, covalently closed circular
      DNA (cccDNA) can persist in nuclei of infected hepatocytes and trigger production
      of infectious virus. Current standard of care treatments against chronic HBV
      infections primarily rely on nucleoside analogs (NA) that inhibit de novo virus
      production by inhibiting the viral reverse transcriptase and, as a consequence,
      reducing virus titers. However, they cannot cure infections, because they do not
      directly target cccDNA persistence. Nevertheless, NA therapies can halt
      progression of liver disease including cirrhosis and can reduce the development
      of hepatocellular carcinoma (HCC). A cure for chronic hepatitis B (CHB) must
      reduce the load of cccDNA or permanently silence transcription from cccDNA, and
      ensure sustained activation of an adaptive immune response that prohibits
      reactivation and spread of residual virus in the liver. As discussed in this
      review, novel technologies enabling genetic destruction of cccDNA and advances in
      our understanding of HBV transcriptional control provide exciting opportunities
      for the future development of curative therapies desperately needed to reduce the
      burden of chronic HBV infections.

PMID- 29453099
TI  - Impact of integrated viral DNA on the goal to clear hepatitis B surface antigen
      with different therapeutic strategies.
AB  - A hallmark of hepatitis B virus (HBV) infection is the presence of hepatitis B
      surface antigen (HBsAg) in the serum of patients. Sustained loss of HBV DNA and
      HBsAg from the blood are main goals for treatment, and considered as functional
      cure. It is rarely achieved with long-term nucleoside analogue treatment though,
      both because cccDNA, the template for viral replication, is not completely
      cleared, and probably also because hepatocytes with HBV DNA integrated into their
      chromosomes persist and continue to produce large amounts of HBsAg. Therefore,
      loss of HBsAg requires that both cccDNA and integrated DNA are cleared or their
      expression blocked. Recent data indicate that this may be achieved in some
      patients by stopping nucleoside analogue treatment, and that HBsAg-levels can be
      reduced by using specific interfering RNA. In the future, targeted degradation or
      disruption of HBV DNA might be possible using genome editing techniques such as
      CRISPR/Cas9.

PMID- 29453100
TI  - Nanoscale zero-valent iron assisted phytoremediation of Pb in sediment: Impacts
      on metal accumulation and antioxidative system of Lolium perenne.
AB  - Lead (Pb) is a highly toxic environmental pollutant, and could result in toxic
      effects on living organisms. The effects of 0, 100, 200, 500, 1000 and 2000 mg/kg
      of nZVI on plant growth, Pb accumulation and antioxidative responses of Lolium
      perenne were investigated. Results showed that the total Pb contents in L.
      perenne with the treatment of low concentrations of nZVI (100, 200 and 500 mg/kg)
      were higher than those in the non-nZVI treatments, and the highest Pb
      accumulation capacity of 1175.40 MUg per pot was observed in L. perenne with the
      treatment of 100 mg/kg nZVI. However, the total Pb contents in L. perenne
      decreased at high concentrations of nZVI (1000 and 2000 mg/kg). This might be
      resulted from the decrease of photosynthetic chlorophyll content and the
      aggravated oxidative stress induced by the high concentration of nZVI, which
      caused the decrease of plant biomass and metal accumulation capacity in plant.
      Moreover, the sequential extraction experiments results showed that the lowest
      acid soluble fraction of Pb in the sediments was found in the treatment with 100
      mg/kg of nZVI, indicating that 100 mg/kg was the optimum concentration for nZVI
      to assist the phytoremediation of Pb-polluted sediment. To conclude, these
      findings provide a promising method to remediate Pb-polluted sediment by nZVI
      assisted phytoremediation.

PMID- 29453101
TI  - Can higher training practice dosage with treadmill slip-perturbation necessarily
      reduce risk of falls following overground slip?
AB  - BACKGROUND: Perturbation training is an emerging paradigm to reduce idiopathic
      falls (without clinical signs or symptoms) in older adults. While a higher threat
      dosage (intensity) in motor learning often directly relates to greater
      adaptation, retention, and generalization, little is known whether increasing the
      practice dosage (repetition) of slip-perturbation training would necessarily
      improve its outcomes. RESEARCH QUESTION: Can higher practice dosage of treadmill
      slip-perturbation training lead to greater generalization to an overground slip
      immediately after the training? METHODS: Forty-five community-dwelling older
      adults (73.5 +/- 5.6 years old) participated in the present study. They were
      conveniently assigned to three groups with equivalent treadmill walking duration:
      treadmill slip-perturbation training group with 40 practice dosage, 24 practice
      dosage, and zero practice dosage (without slip-perturbation). Later on during
      overground walking, all of them were exposed to the same generalization test (a
      novel slip on a walkway). Their recovery outcomes (fall, or no fall; balance
      loss, or no balance loss) and center of mass stability were compared. RESULTS:
      Higher practice dosage did not show significantly less incidence of fall, balance
      loss, or greater stability in comparison to lower practice dosage (p > .05). The
      present study showed that there was no evidence of dose-response relationship
      when the practice dosage was set above the 24 trials of practice dosage in
      treadmill slip-perturbation training. SIGNIFICANCE: Contrary to our hypothesis,
      increased practice dosage (40-slips) in treadmill slip-perturbation training from
      the commonly used threshold (24-slips) did not necessarily benefit immediate
      generalization from treadmill to overground walking among community-dwelling
      older adults.

PMID- 29453102
TI  - Preparation of PLGA/Rose Bengal colloidal particles by double emulsion and layer
      by-layer for breast cancer treatment.
AB  - The use of colloidal particles (CPs) in the transport of drugs is developing
      rapidly thanks to its effectiveness and biosafety, especially in the treatment of
      various types of cancer. In this study Rose Bengal/PLGA CPs synthesized by double
      emulsion (W/O/W) and by electrostatic adsorption (layer-by-layer), were
      characterized and evaluated as potential breast cancer treatment. CPs were
      evaluated in terms of size, zeta potential, drug release kinetics and cell
      viability inhibition efficacy with the triple negative breast cancer cell line
      HCC70. The results showed that both types of CPs can be an excellent alternative
      to conventional cancer treatment by taking advantage of the enhanced permeation
      and retention (EPR) effect, manifested by solid tumors; however, the double
      emulsion CPs showed more suitable delivery times of up to 60% within two days,
      while layer-by-layer showed fast release of 50% in 90 min. Both types of CPs were
      capable to decrease cell viability, which encourage us to further testing in in
      vivo models to prove their efficacy and feasible use in the treatment of triple
      negative breast cancer.

PMID- 29453103
TI  - Free-standing red phosphorous/silver sponge monolith as an efficient and easily
      recyclable macroscale photocatalyst for organic pollutant degradation under
      visible light irradiation.
AB  - Traditional nano-sized photocatalysts in powdery form suffer from difficulties in
      recyclability, and have to be immobilized before practical applications. In this
      study, red phosphorous/silver (red P/Ag) sponge monolith was discovered to be a
      new free-standing macroscale photocatalyst, which was fabricated by a one-pot
      hydrothermal method without using any organic surfactants or templates for the
      first time. The elemental red P not only functioned as a reducing agent in the
      formation of Ag sponge monolith during the synthesis processes, but also as the
      active photocatalyst in-situ immobilized onto the Ag sponge. The as-prepared red
      P/Ag sponge monolith showed enhanced photocatalytic activity than that of
      traditional pure powdery red P by a factor of 3.1 times for organic pollutants
      (i.e. Rhodamine 6G, phenol) degradation under visible light irradiation. The
      enhancement was mainly attributed to the function of Ag sponge served as good
      electron sink to trap photo-generated electrons. More importantly, such free
      standing macroscale photocatalyst can be easily recycled without activity
      deterioration. As a proof of concept, this work provides new insights into not
      only for the development of red P-based elemental photocatalysts, but also for
      the one-pot fabrication of novel free-standing macroscale materials with
      excellent photocatalytic activity for practical environmental applications.

PMID- 29453104
TI  - Controlling shape anisotropy of hexagonal CdS for highly stable and efficient
      photocatalytic H2 evolution and photoelectrochemical water splitting.
AB  - Photocorrosion and low solar conversion efficiency hindered widely applications
      of CdS in photocatalytic (PC) H2 evolution and photoelectrochemical (PEC) water
      splitting. Hence, this work reports the shape anisotropy of hexagonal CdS
      possesses highly stable and efficient PC H2 evolution and PEC water splitting by
      simply mixed diethylenetriamine (DETA) and deionized water (DIW) solvothermal.
      Here we demonstrate that the shape of hexagonal CdS plays an important role in
      their PC activity. The CdS-Nanorod yields optimal 5.4 mmol/g/h PC H2 production
      and photocurrent density 2.63 mA/cm2 at open circuit potential (OCP). The
      enhanced performance is attributed to the effective separation and transport of
      the photogenerated electron-hole pairs, which were verified by PL and transisent
      absorbance. Moreover, hexagonal CdS-Nanorod shows long-term PC H2 production and
      highly stable photocurrent density. As compared with CdS-Nanosphere, the
      hexagonal CdS-Nanorod exhibits 27 times and 19.2 times in H2 production and
      photocurrent density, respectively. What's more, STH efficiency of hexagonal CdS
      Nanorod is 3.23% and an impressive applied bias photon-to-current efficiency
      (ABPE) is 2.63% at 0.134 V (vs. RHE). Temperature is also explored and reported.
      The possible mechanism of PC H2 evolution and PEC water spiltting are proposed
      for CdS-Nanorod. This work may provide a promising strategy to fabricate
      efficient PC and PEC systems for solar-to-fuel energy conversion.

PMID- 29453105
TI  - Highly efficient and selective removal of N-heterocyclic aromatic contaminants
      from liquid fuels in a Ag(I) functionalized metal-organic framework: Contribution
      of multiple interaction sites.
AB  - An adsorbent with multiple interaction sites for the adsorption of nitrogen
      containing compounds (NCCs) has been realized in a silver ion functionalized Cr3+
      based metal-organic framework (Cr)-MIL-101-SO3Ag. The adsorptive denitrogenation
      performance of (Cr)-MIL-101-SO3Ag was evaluated in a batch adsorption system in
      terms of both its adsorption capacity and selectivity, of which, quinoline and
      indole were selected as representative organonitrogen contaminants in liquid
      fuels. (Cr)-MIL-101-SO3Ag could interact with NCCs through multiple ways
      simultaneously, which exhibited about 50% higher adsorption capacity compared to
      (Cr)-MIL-101-SO3H, and a still high level of adsorption amount could be remained
      even in a model fuel where toluene (15% v) was added as a co-solvent and
      benzothiophene (BT) was added as a competitive adsorbate. The highly efficient
      and selective denitrogenation performance, we speculated was a combined results
      of these multiple interaction sites. The immobilized Ag(I) sites could strongly
      interact with NCCs through pi-complexation, which was thought to be responsible
      for its high adsorption capacity, meanwhile, the hard lewis acid site (Cr3+),
      which could preferentially interact with the hard nitrogen bases and the acid
      base interaction between nitrogen bases and remaining -SO3H groups endowed (Cr)
      MIL-101-SO3Ag with high selectivity over BT and other aromatic compounds.
      Futhermore, the enhanced interaction of (Cr)-MIL-101-SO3Ag with NCCs was also
      confirmed from the IR spectra with the significantly enhanced absorbance peak at
      806 or 745 cm-1 observed for QUI and IND, respectively when compared to BT. After
      five successive adsorption-desorption cycles, the adsorption capacity of (Cr)-MIL
      101-SO3Ag was almost unchanged, and the structural stability was well maintained,
      making it a potential adsorbent for deep denitrogenation of liquid fuels.

PMID- 29453106
TI  - Regionalized and vectorial charges transferring of Cd1-xZnxS twin nanocrystal
      homojunctions for visible-light driven photocatalytic applications.
AB  - In photocatalyst designing, quick recombination of photo-generated electron-hole
      pairs in the bulk or on the surface of semiconductors is a major limiting factor
      in achieving high photocatalytic efficiency, which is one of the most knotty
      scientific issues. For this purpose, a series of Cd1-xZnxS twin nanocrystal (NC)
      zinc blende/wurtzite (ZB/WZ) homojunctions photocatalysts were synthesized by a
      facile solvothermal route and innovatively employed in photocatalytic
      degradation. In sample Cd0.6Zn0.4S, ZB and WZ phases have the largest
      distribution and closest interconnection at atomic level. The type-II staggered
      band alignment formed between two phases made photo-generated electrons and holes
      spatially separated to ZB (away from twin plane) and WZ (to twin plane) regions,
      and the ordered arrangement of redox reaction's active sites was then realized
      inside a single semiconductor. Finally, photocatalytic activities of the samples
      were evaluated by degradation of methylene blue (MB) upon visible light
      irradiation. The optimal Cd0.6Zn0.4S NCs without any co-catalyst loading showed
      high photocatalytic activity with degradation efficiency of 95% in 80 min and
      performed excellent photostability. Furthermore, photocatalytic degradation and
      electron transfer mechanisms in Cd0.6Zn0.4S twin NCs are studied particularly.
      Inner twin structure homojunction has provided a new insight into the crystalline
      phase engineering.

PMID- 29453108
TI  - Telomeres and telomerase in heart regeneration.
AB  - Although recent advances have overturned the old view of the human heart as an
      inert postmitotic organ, it is clear that the adult heart's capacity to
      regenerate after an ischemic episode is very limited. Unlike humans, zebrafish
      and other lower vertebrates vigorously regenerate damaged myocardium after
      cardiac injury. Understanding how the zebrafish is able to conserve life-long
      cardiac regeneration capacity while mammals lose it soon after birth is crucial
      for the development of new treatments for myocardial infarction. Mammals and
      lower vertebrates differ markedly in their rates of cardiomyocyte proliferation
      and levels of telomerase activity. Here, we review recent discoveries identifying
      lack of telomerase activity and concomitant telomere dysfunction as natural
      barriers to cardiomyocyte proliferation and cardiac regeneration.

PMID- 29453107
TI  - Body fluid identification using a targeted mRNA massively parallel sequencing
      approach - results of a EUROFORGEN/EDNAP collaborative exercise.
AB  - In a previous study we presented an assay for targeted mRNA sequencing for the
      identification of human body fluids, optimised for the Illumina MiSeq/FGx MPS
      platform. This assay, together with an additional in-house designed assay for the
      Ion Torrent PGM/S5 platform, was the basis for a collaborative exercise within 17
      EUROFORGEN and EDNAP laboratories, in order to test the efficacy of targeted mRNA
      sequencing to identify body fluids. The task was to analyse the supplied dried
      body fluid stains and, optionally, participants' own bona fide or mock casework
      samples of human origin, according to specified protocols. The provided primer
      pools for the Illumina MiSeq/FGx and the Ion Torrent PGM/S5 platforms included 33
      and 29 body fluid specific targets, respectively, to identify blood, saliva,
      semen, vaginal secretion, menstrual blood and skin. The results demonstrated
      moderate to high count values in the body fluid or tissue of interest with little
      to no counts in non-target body fluids. There was some inter-laboratory
      variability in read counts, but overall the results of the laboratories were
      comparable in that highly expressed markers showed high read counts and less
      expressed markers showed lower counts. We performed a partial least squares (PLS)
      analysis on the data, where blood, menstrual blood, saliva and semen markers and
      samples clustered well. The results of this collaborative mRNA massively parallel
      sequencing (MPS) exercise support targeted mRNA sequencing as a reliable body
      fluid identification method that could be added to the repertoire of forensic MPS
      panels.

PMID- 29453109
TI  - Genetic basis of diabetic kidney disease and other diabetic complications.
AB  - Diabetic kidney disease and other long-term complications are common in diabetes,
      and comprise the main cause of co-morbidity and premature mortality in
      individuals with diabetes. While familial clustering and heritability have been
      reported for all diabetic complications, the genetic background and the molecular
      mechanisms remain poorly understood. In recent years, genome-wide association
      studies have identified a few susceptibility loci for the renal complications as
      well as for diabetic retinopathy, diabetic cardiovascular disease and mortality.
      As for many complex diseases, the genetic factors increase the risk of
      complications in concert with the environment, and certain associations seem
      specific for particular conditions, for example, SP3-CDCA7 associated with end
      stage renal disease only in women, or MGMT and variants on chromosome 5q13
      associated with cardiovascular mortality only under tight glycaemic control. The
      characterization of the phenotypes is one of the main challenges for genetic
      research on diabetic complications, in addition to an urgent need to increase the
      number of individuals with diabetes with high quality phenotypic data to be
      included in future genetic studies.

PMID- 29453110
TI  - Genetics of type 1 diabetes.
AB  - Type 1 diabetes is the most common autoimmune disorder in childhood,
      characterized by the development of autoimmunity through unknown environmental
      insults in genetically susceptible individuals. There are now over 50 regions of
      the genome that harbor type 1 diabetes susceptibility genes, with much of the
      genetic risk now well-defined in youth of Northern European ancestry. The impact
      of these genetic variants on initiation and progression of the autoimmune process
      (islet autoimmunity) is now being understood; however, studies are only now being
      conducted to understand the function of the variants associated with type 1
      diabetes risk. The characteristics of genetic risk of type 1 diabetes across the
      age spectrum suggests extensive complexity in biological and environmental
      mechanisms. We propose that both genetic and environmental factors attributed to
      type 1 and type 2 diabetes may contribute to beta-cell death through multiple
      mechanisms, leading to the clinical outcome of type 1 diabetes.

PMID- 29453111
TI  - Febrile infection-related epilepsy syndrome (FIRES): therapeutic complications,
      long-term neurological and neuroimaging follow-up.
AB  - PURPOSE: To understand the long-term neurological outcomes and chronological
      changes of brain MRIs in patients with febrile infection-related epilepsy
      syndrome (FIRES). METHODS: From December 2000 to May 2016, 29 patients diagnosed
      with FIRES were collected retrospectively. The demographic distribution, clinical
      manifestations, neuroimaging findings, and treatment methodology were described.
      Follow-up clinical outcomes and chronological evolution of neuroimaging findings
      were analyzed. RESULTS: The median age of disease onset was 8.9 years. The median
      duration of hospitalization was 87 days. During the period of hospitalization,
      more than 50% of patients exhibited complications such as skin rash, liver
      function impairment, and arrhythmia. Abnormal findings were found in 38% of
      neuroimaging studies in the initial study and in 87% of the follow-up brain MRI.
      Focal abnormal signal changes over the periventricular white matter suggested the
      more extensive lesions would be associated with a poorer clinical outcome. The
      median duration of follow-up was 5 years in 23 patients. In total, 87% of
      patients exhibited residual and/or refractory epilepsy. Regarding cognitive
      function, 26% of patients had normal intelligence quotient, 26% had learning
      disability and mild to moderate mental retardation, and 48% had severe mental
      retardation or vegetative status. The mortality rate at acute stage was 10%, and
      that at chronic stage was 13%. CONCLUSIONS: Liver function impairment, skin rash,
      and arrhythmia are frequently seen during hospitalization for FIRES at the acute
      stage of disease course. The higher grade of periventricular white matter lesions
      suggested poorer neurological outcomes. Studies on the pathomechanism of FIRES
      are crucially needed so that new treatment strategies for FIRES can be developed,
      which may improve long-term outcomes.

PMID- 29453112
TI  - Pattern and determinants of self-reported enacted stigma among rural dwellers
      living with epilepsy attending a tertiary health facility in Enugu State Nigeria.
AB  - PURPOSE: Epilepsy related stigma is a barrier to recovery and has been linked to
      a broad range of psychosocial consequences and has the potential to influence the
      provision of care to people with epilepsy. Understanding the determinants of
      enacted stigma in epilepsy is relevant in the understanding of the burden of
      epilepsy in Nigeria. METHOD: Using a semi-structured questionnaire, a cross
      sectional descriptive study was conducted among rural dwellers receiving
      treatment for epilepsy in a tertiary referral specialist hospital in Enugu, south
      east Nigeria. RESULTS: The participants consisted of 108 patients, 63% of whom
      were males. Most patients 99(91.7%) reported experiencing stigma in the past. The
      commonest forms of enacted stigma were being regarded as having 'spiritual
      attack' 88(81.5%) and restraining from interacting with others 49(45.4%). Most
      individuals who received nonorthodox treatment 55(55.6%) experienced stigma.
      Severely stigmatized individuals were more likely to be females. Age of onset of
      epilepsy, use of non-orthodox treatment, seizures occurrence in public places and
      the presence of physical injuries positively correlated with enacted stigma.
      CONCLUSIONS: The burden of epilepsy related enacted stigma is high among rural
      dwellers attending a tertiary medical outpatient clinic in Enugu, southeast
      Nigeria.

PMID- 29453113
TI  - Epidemiological profile of epilepsy in low income populations.
AB  - Epilepsy is a global disease with an unequal distribution. About 80% of the
      affected individuals reside in low and middle income countries. The incidence and
      prevalence of epilepsy in low income populations is higher than in the rest of
      the world, this is partly explained by some risk factors such as head trauma,
      perinatal injury and CNS infections, which are more common in poor regions,
      especially in rural areas. Epilepsy is considered a treatable condition with high
      rates of therapeutic response. About three fourths of patients achieve control of
      the disease with the use of antiepileptic drugs, however, despite this benign
      prognosis, over 75% of patients from low income populations do not receive
      treatment at all. The cultural beliefs, the inequity in the distribution of
      public health services, the inadequate supply of antiepileptic drugs, the low
      number of neurologists involved in the attention of epilepsy, and the social
      stigma, are the main reasons that increase the treatment gap and the burden of
      disease in low income populations with epilepsy. We conducted a narrative review
      regarding the epidemiology of epilepsy in low income populations by searching
      PubMed, EMBASE, Google Scholar and thoroughly examining relevant bibliographies.
      This review aims to summarize the main epidemiological aspects of epilepsy in
      LMIC, emphasizing on incidence, prevalence, socio-demographic profile, TG, social
      stigma and QoL.

PMID- 29453114
TI  - Levetiracetam monotherapy for the treatment of infants with epilepsy.
AB  - PURPOSE: Levetiracetam is a broad-spectrum anti-epileptic drug that is effective
      against both focal and generalized epilepsies. In this study, we aimed to
      evaluate the efficacy, tolerability and safety of levetiracetam monotherapy in
      the management of different seizure types in children with epilepsy under the age
      of two. METHOD: This retrospective study was conducted on children with a
      diagnosis of epilepsy from January 2014 to January 2017. To be included in the
      study, patients were required to be less than two years of age at the time
      levetiracetam was initiated as initial monotherapy and to be followed clinically
      for at least 6 months. RESULTS: Of the 92 patients, 61 (66%) patients were
      seizure free. Fifty-eight percent of the patients (31 of 53) with focal epilepsy
      were seizure free and 77% (30 of 39) generalized epilepsy were seizure free. We
      found that levetiracetam monotherapy was effective in both focal and generalized
      epilepsy. Levetiracetam monotherapy was significantly more effective in patients
      with unknown etiologies (p = 0.004). Seizure freedom rate under levetiracetam
      monotherapy was significantly higher in patients with normal psychomotor
      development (p = 0.000). Seizure freedom rate under levetiracetam monotherapy was
      significantly higher in patients with unknown etiologies and normal psychomotor
      development. Normal psychomotor development was the strongest predictor of
      seizure control under levetiracetam monotherapy (OR = 6; 95% CI = 2.3-16.0; p <
      0.001). Five children (1%) reported irritability. No hematological or
      biochemical, or behavioral adverse side effects except irritability were reported
      in any children. No patient discontinued levetiracetam therapy because of
      treatment-related side effects. CONCLUSION: Our study showed levetiracetam to be
      an effective, well tolerated and safe agent for the treatment of a variety of
      seizure types and etiologies seen in infants.

PMID- 29453115
TI  - Cumulative energy demand and global warming potential of a building-integrated
      solar thermal system with/without phase change material.
AB  - Building-integrated solar thermal (BIST) systems are a specific type of solar
      thermal systems which are integrated into the building and they participate in
      building functionality. The present article is about the life-cycle assessment of
      different options of a BIST system (Mediterranean climatic conditions: Ajaccio,
      France). The environmental profile of the studied configurations is assessed by
      means of CED (cumulative energy demand), GWP (global warming potential) and EPBT
      (energy payback time). The proposed configurations (for the collector) include:
      i) a system without PCM (phase change material) using only rock wool as
      insulation and ii) a system with PCM (myristic acid) and rock wool. Concerning
      life-cycle results based on CED and GWP 100a (scenario without recycling), the
      configuration without PCM shows 0.67 MJprim/kWh and 0.06 kg CO2.eq/kWh while the
      configuration with PCM presents 0.74 MJprim/kWh and 0.08 kg CO2.eq/kWh. Regarding
      EPBT, if the inputs for pumping/auxiliary heating are not taken into account,
      both configurations (with/without PCM) have almost the same EPBT (about 1.3
      years). On the other hand, if the inputs for pumping/auxiliary heating are
      considered, EPBT is lower for the system with PCM. In addition, scenarios with
      recycling have been examined and the results demonstrate that recycling
      considerably improves the environmental profile of the studied configurations.

PMID- 29453116
TI  - Developing a methodology for real-time trading of water withdrawal and waste load
      discharge permits in rivers.
AB  - In this paper, a new methodology is proposed for the real-time trading of water
      withdrawal and waste load discharge permits in agricultural areas along the
      rivers. Total Dissolved Solids (TDS) is chosen as an indicator of river water
      quality and the TDS load that agricultural water users discharge to the river are
      controlled by storing a part of return flows in some evaporation ponds. Available
      surface water withdrawal and waste load discharge permits are determined using a
      non-linear multi-objective optimization model. Total available permits are then
      fairly reallocated among agricultural water users, proportional to their arable
      lands. Water users can trade their water withdrawal and waste load discharge
      permits simultaneously, in a bilateral, step by step framework, which takes
      advantage of differences in their water use efficiencies and agricultural return
      flow rates. A trade that would take place at each time step results in either
      more benefit or less diverted return flow. The Nucleolus cooperative game is used
      to redistribute the benefits generated through trades in different time steps.
      The proposed methodology is applied to PayePol region in the Karkheh River
      catchment, southwest Iran. Predicting that 1922.7 Million Cubic Meters (MCM) of
      annual flow is available to agricultural lands at the beginning of the
      cultivation year, the real-time optimization model estimates the total annual
      benefit to reach 46.07 million US Dollars (USD), which requires 6.31 MCM of
      return flow to be diverted to the evaporation ponds. Fair reallocation of the
      permits, changes these values to 35.38 million USD and 13.69 MCM, respectively.
      Results illustrate the effectiveness of the proposed methodology in the real-time
      water and waste load allocation and simultaneous trading of permits.

PMID- 29453117
TI  - Performance of integrated ferrate-polyaluminum chloride coagulation as a
      treatment technology for removing freshwater humic substances.
AB  - Ferrate-based technologies can play versatile roles in water treatment because of
      their potential for in situ production and because they do not form any harmful
      by-products. We compared the oxidative performance of Fe(VI) generated by an
      electrochemical process, with H2O2-UV irradiation (a standard oxidation process)
      for removing Suwannee River natural organic matter. It took only 5 min for Fe(VI)
      (Fe: 1.67 * 10-4 M) to reduce the fluorescence intensity of a humic-like
      fluorophore by 36% of the original value; in contrast, it took 120 min of
      irradiation using H2O2-UV ([OH] ~ 1.8 * 10-13 M) to remove 68% of the original
      value. In addition to the short reaction time, ferrate can also form aggregates
      that can remove turbidity and adsorb organics and other contaminants present in
      water. Simultaneous addition of ferrate and polyaluminum chloride (PACl) to
      unfiltered natural water displayed the most efficient reduction of UVA254,
      primarily under acidic conditions. Ferrate pre-oxidation followed by PACl
      coagulation was the most effective process for reducing turbidity and
      chromaticity, because of the effects arising from the coagulation of ferrate that
      resulted in Fe(III)(s) species. Ferrate pre-oxidation generated low-molecular
      weight UVA254-absorbing organics, whose dissolved organic matter (DOM) peak at
      1250 Da was removed by PACl coagulation. Neither the initial pH nor the process
      order significantly affected the removal of organic carbon by the integrated
      ferrate-PACl process.

PMID- 29453118
TI  - Effects of forest regeneration practices on the flux of soil CO2 after clear
      cutting in subtropical China.
AB  - Reforestation after clear-cutting is used to facilitate rapid establishment of
      new stands. However, reforestation may cause additional soil disturbance by
      affecting soil temperature and moisture, thus potentially influencing soil
      respiration. Our aim was to compare the effects of different reforestation
      methods on soil CO2 flux after clear-cutting in a Chinese fir plantation in
      subtropical China: uncut (UC), clear-cut followed by coppicing regeneration
      without soil preparation (CC), clear-cut followed by coppicing regeneration and
      reforestation with soil preparation, tending in pits and replanting (CCRP), and
      clear-cut followed by coppicing regeneration and reforestation with overall soil
      preparation, tending and replanting (CCRO). Clear-cutting significantly increased
      the mean soil temperature and decreased the mean soil moisture. Compared to UC,
      CO2 fluxes were 19.19, 37.49 and 55.93 mg m-2 h-1 higher in CC, CCRP and CCRO,
      respectively (P < 0.05). Differences in CO2 fluxes were mainly attributed to
      changes in soil temperature, litter mass and the mixing of organic matter with
      mineral soil. The results suggest that, when compared to coppicing regeneration,
      reforestation practices result in additional CO2 released, and that regarding the
      CO2 emissions, soil preparation and tending in pits is a better choice than
      overall soil preparation and tending.

PMID- 29453119
TI  - An analysis of environmental incidents for a national Antarctic program.
AB  - Research stations in Antarctica are concentrated on scarce ice-free habitats.
      Operating these stations in the harsh Antarctic climate provides many challenges,
      including the need to handle bulk fuel and cargo increasing the risk of
      environmental incidents. We examined 195 reports of environmental incidents from
      the Australian Antarctic Program, spanning six years, to investigate the impacts
      and pathways of contemporary environmental incidents. Fuel and chemical spills
      were most common, followed by biosecurity incursions. The majority of reports
      were assessed as having insignificant actual impacts. Either the incidents were
      small, or active, rapid response and mitigation procedures minimised impact.
      During the period only one spill report (4000 l) was assessed as a 'high' impact.
      This is despite over 13 million litres of diesel utilised. The majority of
      incidents occurred within the existing station footprints. The pathways leading
      to the incidents varied, with technical causes predominately leading to spills,
      and procedural failures leading to biosecurity incursions. The large number of
      reports with inconsequential impacts suggest an effective environmental
      management system with a good culture of reporting environmental incidents. Our
      findings suggest that the key to continual improvement in an ongoing
      environmental management system is to learn from incidences and take action to
      prevent them occurring again, with an end-goal of minimising the residual risk as
      much as possible.

PMID- 29453120
TI  - Mycobiota and co-occurrence of mycotoxins in South African maize-based opaque
      beer.
AB  - Beer, a beverage consumed throughout the world, is mainly derived from cereals.
      In this study, fungal and mycotoxin contamination, as well as the physicochemical
      properties of maize-based opaque beer (umqombothi) obtained from the Gauteng
      province of South Africa, was investigated. The mean water activity, pH and total
      titratable acidity of the analysed beer samples were 0.91, 3.76 and 1.20% lactic
      acid, respectively. The investigation revealed Aspergillus, Penicillium, Phoma
      and Saccharomyces as the predominant fungal genera with a mean fungal load of
      3.66 * 105 CFU/mL. Among the mycotoxigenic fungal species recovered, Aspergillus
      flavus had the highest incidence of 26%. Previously unreported strains such as P.
      chrysogenum strain AD25, A. sydowii strain AD 22 and A. tritici strain AD 11 were
      found. Furthermore, mycotoxin quantitative analysis via liquid chromatography
      tandem mass spectrophotometry showed that deoxynivalenol was the dominant
      mycotoxin occurring in 84% of the samples. This was followed by enniatin B that
      occurred in 75% of samples ranging from 12 to 44 MUg/L and fumonisin B1 (FB1)
      (incidence of 53% at a maximum level of 182 MUg/L). Generally, there was low
      occurrence aflatoxins, whereas T-2, HT-2, nivalenol, zearalenone, 3- and 15
      acetyl-deoxynivalenol were not detected. All the samples analysed had safe levels
      of mycotoxins tested but were contaminated by at least two mycotoxins that could
      pose some additive or synergistic health effects among consumers. On average: a
      60 kg adult consuming 1-6 L/day of the beer was exposed to FB1 + FB2 at an
      estimated 2.20-13.20 MUg/kg body weight/day. These values were far above the
      maximum tolerable daily intake of 2 MUg/kg bw/day established by the Joint
      FAO/WHO Expert Committee on Food Additives (JECFA). The study demonstrates that
      consumption of umqombothi can significantly enhance dietary exposure to multiple
      mycotoxins among consumers, and therefore accentuates the need for strategies
      aimed at reducing toxigenic fungal colonization and mycotoxin contamination in
      the beer processing chain.

PMID- 29453121
TI  - Regenerable urchin-like Fe3O4@PDA-Ag hollow microspheres as catalyst and
      adsorbent for enhanced removal of organic dyes.
AB  - In this work, novel urchin-like Fe3O4@polydopamine (PDA)-Ag hollow microspheres
      have been prepared via a facile synthesis method by in situ reduction and growth
      of Ag nanoparticles on mussel-inspired PDA layers coated on Fe3O4 hollow cores.
      The catalytic reduction efficiency and adsorption performance of the as-prepared
      urchin-like Fe3O4@polydopamine (PDA)-Ag hollow microspheres for model organic
      dyes (i.e., methylene blue and rhodamine B) under varying pH condition have been
      systematically investigated, which are demonstrated to be significantly enhanced
      as compared to that of spherical (relatively smooth) solid Fe3O4@PDA-Ag
      microspheres. The as-prepared urchin-like Fe3O4@PDA-Ag hollow microspheres show
      high reusability, easy separability, and fast regeneration ability, with no
      obvious drop in the catalytic and adsorption efficiency after cyclic reuse. The
      versatile PDA coatings on the urchin-like microspheres allow further surface
      functionalization for development of multifunctional catalyst and adsorbent
      materials. This work provides a very useful and facile methodology for
      synthesizing and tuning the urchin-like morphology of Fe3O4@PDA-Ag microspheres,
      with great potential applications in catalysis and wastewater treatment.

PMID- 29453122
TI  - Assessment of the potential hazard represented by natural raw materials
      containing mineral fibres-The case of the feldspar from Orani, Sardinia (Italy).
AB  - This work describes the nature of the potentially hazardous fibrous amphibole
      found in the Orani's feldspar mine (Sardinia, Italy). To identify its nature, a
      protocol of analysis including morphometric, chemical and crystallographic
      characterizations was applied. Thanks to this approach, it was possible to
      classify the observed fibres as tremolite after comparing chemical data, SEM/TEM
      observations, FTIR/ Raman spectra and X-ray diffraction data with those reported
      for a standard sample. The unit cell parameters of the investigated tremolite
      phase are a = 9.82(1) A, b = 18.08(3) A, c = 5.27(1) A, and the angle beta
      corresponds to 104.4(1) degrees . The mean concentration of asbestos tremolite in
      the Orani's feldspar is 0.28 wt%. Most of the fibres (0.26 wt%) are respirable
      'regulated' fibres, representing a potential hazard. Because the total amount of
      tremolite in the sample is 0.6 wt%, a large fraction of it has a crystal habit
      other than fibrous-asbestiform or acicular. The obtained results allowed us to
      suggest possible solutions for a safe exploitation and mineral processing of the
      Orani's mine. The procedure proposed herein may be a general tool suitable to
      identify the mineralogical nature of fibrous minerals in raw materials and assess
      if they may represent a potential health/environmental hazard.

PMID- 29453124
TI  - Exploring the function of bacterial chemotaxis.
AB  - Bacterial chemotaxis is a classical subject: our knowledge of its molecular
      pathway has grown very detailed, and experimental observations, as well as
      mathematical models of the dynamics of chemotactic populations, have a history of
      several decades. This should not lead to the conclusion that only minor details
      are left to be understood. Indeed, it is believed that bacterial chemotaxis is
      under selection for efficiency, yet the underlying functional forces remain
      largely unknown. These aspects are discussed here by the presentation of
      illustrative examples related to the role of adaptation and signal integration.
      Both are expected to be important in ecologically relevant conditions, where
      chemotaxis should be strongly coupled with metabolism and growth, due to the
      presence of diverse chemoattractant cues and their active consumption by multiple
      types of bacteria competing for growth.

PMID- 29453123
TI  - An experiential model of education introduced to improve the confidence of
      student midwives in undertaking second stage management of the perineum (SSMP).
AB  - BACKGROUND AND OBJECTIVE: the limited availability of high quality evidence
      related to second stage management of the perineum (SSMP) combined with a
      perceived shift in UK practice towards a 'hands off' the perineum/fetal head
      approach are likely to have impacted significantly on student midwives'
      understanding of SSMP. This paper presents a classroom based educational session
      using low fidelity simulation, which was designed in response to student feedback
      and aimed to improve confidence in this skill. DESIGN: reflective teaching
      practice, based on evaluation of SSMP teaching. SETTING: an undergraduate
      midwifery programme based at an inner city university in London UK. PARTICIPANTS:
      student midwives. FINDINGS: the education session based on Kolb's experiential
      approach to learning appeared to address gaps in the previous teaching which was
      identified by students. The Classroom setting offered students a supportive
      setting in which to experiment with different SSMP approaches with a view to
      personalising care and without compromising safety. CONCLUSIONS AND IMPLICATIONS
      FOR PRACTICE: although further longitudnal research is needed, the experiential
      model appears to offer a low resource approach to teaching SSMP and has potential
      application in other countries.

PMID- 29453125
TI  - Discussion of "Patients with sentinel lymph node positive melanoma: Who needs
      completion lymph node dissection?"

PMID- 29453126
TI  - PGY-specific benchmarks improve resident performance on Fundamentals of
      Laparoscopic Surgery tasks.
AB  - BACKGROUND: Although expert proficiency times for Fundamentals of Laparoscopic
      Surgery (FLS) tasks exist, these times are not always attainable for junior
      residents. We hypothesize that post-graduate year (PGY)-specific benchmarks will
      improve resident performance of FLS tasks. METHODS: In 2014, PGY-specific
      benchmarks were developed for FLS tasks for PGY1-PGY4 general surgery residents
      by averaging completion times for each task from 2007 to 2013. Resident
      performance on each FLS task and overall performance was compared for PGY1-PGY4
      residents in the 2007-2013 group and the 2014-2016 group, before and after
      implementation of PGY-specific benchmarks. RESULTS: There was a significant
      improvement in FLS performance in the 2014-2016 group at the PGY1 (p = 0.01),
      PGY2 (p < 0.01), and PGY3 (p = 0.01) levels, but no difference at the PGY4 level
      (p = 0.71). CONCLUSIONS: PGY-specific benchmarks may improve efficacy of
      laparoscopic skills training for junior residents, increasing the efficiency of
      skill development.

PMID- 29453127
TI  - Generation of D1-1 TALEN isogenic control cell line from Dravet syndrome patient
      iPSCs using TALEN-mediated editing of the SCN1A gene.
AB  - Dravet syndrome (DS) is an infantile epileptic encephalopathy mainly caused by de
      novo mutations in the SCN1A gene encoding the alpha1 subunit of the voltage-gated
      sodium channel Nav1.1. As an in vitro model of this disease, we previously
      generated an induced pluripotent stem cell (iPSC) line from a patient with DS
      carrying a c.4933C>T (p.R1645*) substitution in SCN1A. Here, we describe
      developing a genome-edited control cell line from this DS iPSC line by
      substituting the point mutation with the wild-type residue. This artificial
      control iPSC line will be a powerful tool for research into the pathology of DS.

PMID- 29453128
TI  - Generation of a human iPSC line from a patient with congenital glaucoma caused by
      mutation in CYP1B1 gene.
AB  - The human iPSC cell line, GLC-FiPS4F1 (ESi047-A), derived from dermal fibroblast
      from the patient with congenital glaucoma caused by the mutation of the gene
      CYP1B1, was generated by non-integrative reprogramming technology using OCT3/4,
      SOX2, CMYC and KLF4 reprogramming factors.

PMID- 29453129
TI  - Efficient visible light induced synthesis of silver nanoparticles by Penicillium
      polonicum ARA 10 isolated from Chetomorpha antennina and its antibacterial
      efficacy against Salmonella enterica serovar Typhimurium.
AB  - The green synthesis of silver nanoparticles (AgNPs) using biological systems such
      as fungi has evolved to become an important area of nanobiotechnology. Herein, we
      report for the first time the light-induced extracellular synthesis of silver
      nanoparticles using algicolous endophytic fungus Penicillium polonicum ARA 10,
      isolated from the marine green alga Chetomorpha antennina. Parametric
      optimization, including the concentration of AgNO3, fungal biomass, ratio of cell
      filtrate and AgNO3, pH, reaction time and presence of light, was done for rapid
      AgNPs production. The obtained silver nanoparticles (AgNPs) were characterized by
      UV-Visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, Raman
      spectroscopy and Transmission electron microscopy (HRTEM-EDAX). The AgNPs showed
      a characteristic UV-visible peak at 430 nm with an average size of 10-15 nm. The
      NH stretches in FTIR indicate the presence of protein molecules. The Raman
      vibrational bands suggest that the molecules responsible for the reduction and
      stability of AgNPs were extracellular proteins produced by P.polonicum.
      Antibacterial evaluation of AgNPs against the major foodborne bacterial pathogen
      Salmonella enterica serovar Typhimurium MTCC 1251, was assessed by well
      diffusion, Minimum inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC) assay. Killing kinetic studies revealed complete killing of
      the bacterial cells within 4 h and the bactericidal nature of synthesized
      nanoparticles was confirmed by fluorescent microscopy and scanning electron
      microscopy. Furthermore, the bactericidal studies with Transmission electron
      microscopy (TEM) at different time intervals explored the presence of AgNPs in
      the cell wall of S.Typhimurium at about 30 min and the complete bacterial lysis
      was found at 24 h. The current research opens an insight into the green synthesis
      of AgNPs and the mechanism of bacterial lysis by direct damage to the cell wall.

PMID- 29453130
TI  - Charting the development of cognitive mapping.
AB  - Developmental research beginning in the 1970s has suggested that children's
      ability to form cognitive maps reaches adult levels during early adolescence.
      However, this research has used a variety of testing procedures, often in real
      world environments, which have been difficult to share widely across labs and to
      use to probe components of mapping, individual differences in success, and
      possible mechanisms of development and reasons for individual variation. In this
      study, we charted the development of cognitive mapping using a virtual navigation
      paradigm, Silcton, that allows for testing samples of substantial size in a
      uniform way and in which adults show marked individual differences in the
      formation of accurate route representations and/or in route integration. The
      current study tested children aged between 8 and 16 years. In terms of components
      of normative development, children's performance reached adult levels of
      proficiency at around age 12, but route representation progressed significantly
      more quickly than route integration. In terms of individual differences, by age
      12 children could be grouped into the same three categories evident in adults:
      imprecise navigators (who form only imprecise ideas of routes), non-integrators
      (who represent routes more accurately but are imprecise in relating two routes),
      and integrators (who relate the two routes and, thus, form cognitive maps). Thus,
      individual differences likely originate during childhood. In terms of correlates,
      perspective-taking skills predicted navigation performance better than mental
      rotation skills, in accord with the view that perspective taking operates on
      extrinsic spatial representations, whereas mental rotation taps intrinsic spatial
      representations.

PMID- 29453131
TI  - The incidence of associated abnormalities in patients with sacrococcygeal
      teratoma.
AB  - BACKGROUND: Gross genetic causes for SCT are unknown; however, it might be
      associated with other abnormalities. We assessed the incidence of associated
      abnormalities in a large national cohort of neonates with SCT and aimed to
      identify predictive risk factors. PROCEDURE: The medical records were reviewed of
      235 consecutive neonates with SCT treated at the six pediatric surgical centers
      in the Netherlands from 1970 to 2010. Potential risk factors for associated
      abnormalities analyzed included sex, gestational age, tumor-volume/histology and
      Altman-classification. RESULTS: In 76 patients (32.3%) at least one associated
      abnormality was diagnosed, with hydronephrosis as the most common (16.2%) and hip
      dysplasia in 4.3%. Multiple abnormalities were documented for 21 (9.0%).
      Prematurity and Altman type IV SCT were associated with an increased risk of any
      associated abnormality. No association between increased tumor-volume and
      hydronephrosis or hip dysplasia was found. Patients with type IV Altman SCT had a
      fourfold risk of suffering from hydronephrosis compared to Altman type I SCT.
      CONCLUSIONS: SCT was associated with other abnormalities in one-third of
      children. Some were tumor-related while others were related to prematurity or
      occurred sporadically. In contrast to clinically obvious anomalies, hip dysplasia
      or hydronephrosis might be latently present with more subtle clinical
      presentation. We therefore suggest renal- and hip-ultrasound in all patients,
      certainly those with Altman type IV SCT. LEVEL OF EVIDENCE RATING: Level II
      (retrospective study).

PMID- 29453132
TI  - Malrotation is not associated with adverse outcomes after cardiac surgery in
      patients with heterotaxy syndrome.
AB  - BACKGROUND: Patients with heterotaxy syndrome (HS) often have asymptomatic
      malrotation. There is a lack of consensus regarding the management of these
      patients, particularly in patients with complex congenital heart disease (CHD).
      We sought to describe the prevalence of malrotation and incidence of volvulus in
      a population of patients with complex CHD and to identify the impact of
      malrotation on morbidity and mortality following cardiac surgery. METHODS: We
      performed a retrospective review of all patients with HS and complex CHD who
      required cardiac surgery in the first year of life at a single center between
      October 1995 and September 2015. Malrotation was diagnosed by abdominal imaging
      or by direct inspection during abdominal surgery. Demographic data was collected
      along with details of hospitalization following cardiac and GI surgeries.
      Descriptive analysis along with appropriate hypothesis testing was conducted to
      evaluate the results. RESULTS: We identified 49 patients with HS, 42 with single
      ventricle anatomy and 7 with biventricular anatomy. Of the 49 patients, 29 (59%)
      were diagnosed with malrotation, 6 (12%) had normal intestinal rotation, and 14
      (29%) had no evaluation of intestinal rotation. The prevalence of malrotation in
      the population who underwent abdominal imaging was 29 out of 35 (83%). There was
      no difference in survival following cardiac surgery between patients with
      malrotation and those with unknown or normal intestinal anatomy. Comparing
      patients with malrotation and patients with normal or unknown intestinal
      rotation, there was also no difference in surrogate markers of morbidity. Of the
      29 patients with known malrotation, only 2 patients (7%) underwent therapeutic
      Ladd procedures and 19 (65%) underwent prophylactic Ladd procedures. CONCLUSIONS:
      We conclude that the outcomes following cardiac surgery for patients with HS are
      not impacted by the presence of malrotation. Furthermore, we also found that the
      incidence of volvulus in the studied group is low. Given these findings, and the
      understanding that patients with HS and significant CHD are frequently tenuous
      and high risk surgical candidates, we do not believe performing prophylactic Ladd
      procedures is warranted. LEVEL OF EVIDENCE: III.

PMID- 29453133
TI  - Mortality after emergency abdominal operations in premature infants.
AB  - CONTEXT/BACKGROUND: To determine risk of 30-day mortality for premature infants
      undergoing abdominal operations during the first 2 months of life and to identify
      risk factors for perioperative mortality using available demographic and clinical
      variables of interest. BASIC PROCEDURES: Retrospective descriptive analysis of
      premature infants (gestational age less than or equal to 36weeks) undergoing
      abdominal operations during the first 2 months of life using the American College
      of Surgeon's National Surgical Quality Improvement Project Pediatric (NSQIP-P,
      2012-2015) database. A stepwise logistic regression model incorporating multiple
      demographic and clinical factors was constructed to identify independent
      predictors of 30-day mortality. FINDINGS: A total of 1554 premature infants were
      identified who underwent abdominal operations during the first 2 months of life.
      Unadjusted 30-day mortality ranged from 31% for infants born <24weeks gestational
      age to 4.9% for those born at 35-36weeks. Increased gestational age corresponded
      to decreased risk of mortality but week-by-week was not independently predictive
      of mortality in multivariate modeling. Female sex (aOR 1.51, 95% C.I. 1.08-2.10,
      p=0.014), inotrope support (aOR 3.46, 95% C.I. 2.43-4.92, p<0.001), ventilator
      use (aOR 2.86, 95% C.I. 1.56-5.25, p<0.001) and American Society of
      Anesthesiologists (ASA) class 3 (aOR 4.14, 95% C.I. 1.58-10.81, p=0.004) at time
      of operation were all associated with significantly increased risk of 30-day
      mortality. On stepwise logistic regression incorporating only those variables
      with statistical significance, female sex, inotrope, and ventilator support
      retained statistical significance. CONCLUSIONS: Premature infants undergoing
      abdominal operations during the first 2 months of life have expectedly high risk
      of 30-day mortality. Female sex, inotrope, and ventilator support are
      independently associated with increased risk of mortality and can be incorporated
      into a model where, if present, risk of mortality is greater than 14.2%. LEVEL OF
      EVIDENCE: Level III.

PMID- 29453134
TI  - A dose-dependent relationship between copper burden in female urchin gonads and
      developmental impairment of their offspring.
AB  - We examined transgenerational effects of exposure to copper on early development
      of offspring in the urchin Evechinus chloroticus, and whether parental exposure
      mediated offspring response to a further low level exposure to copper during
      early development. Month-long exposure to elevated copper (25 MUgL-1) in the
      laboratory increased copper in gonads of both males and females and reduced gonad
      size by almost half. There was a negative relationship between adult size and
      copper burden. Normal larval development and larval size four days after
      fertilization were both strongly, negatively related to the amount of copper in
      female gonads in a dose-dependent manner, but fertilization success was
      unaffected. This demonstrates a transgenerational effect of maternal exposure to
      copper pollution on offspring performance that is mediated by individual traits
      of females, but no evidence of strong paternal effects, nor of a low level of
      copper in the water in which early development occurs.

PMID- 29453135
TI  - Dual inhibitors of the pro-survival proteins Bcl-2 and Mcl-1 derived from natural
      compound meiogynin A.
AB  - Thirty analogues of natural meiogynin A, a pan-Bcl-2 inhibitor, were prepared in
      order to elaborate cytotoxic compounds on specific cancer cells overexpressing
      one or more proteins of the Bcl-2 family. The interaction of all the new
      analogues with Bcl-xL, Mcl-1 and Bcl-2 proteins was first evaluated by
      fluorescence polarization assay (FPA) and showed that modulation of the lateral
      chain has a dramatic impact as subtle changes significantly modify the activity
      on the target proteins. The acetoxymethyl prodrugs of the two most active
      compounds were then elaborated to determine their cytotoxicity on B cell lines. A
      strong cytotoxic effect on BL2, RS4;11 and H929 cells was observed with a
      triazole prodrug that induces apoptosis.

PMID- 29453136
TI  - Corrigendum to "Implementing the D4F in a robust model, allowing for enhanced
      comparison, prioritisation and grouping of NMs" [Regul. Toxicol. Pharmacol. 92
      (2018) 207-212].

PMID- 29453137
TI  - Scientific evidence on perineal trauma during labor: Integrative review.
AB  - OBJECTIVE: To assess the scientific evidence for management and preservation of
      perineal integrity during the expulsive stage of labor. STUDY DESIGN: Integrative
      review that employed the Population, Intervention, Comparison, Outcome strategy
      to formulate the research question: Which perineal measure(s) is(are) effective
      in maintaining perineal integrity during labor? The search was performed in the
      databases MEDLINE, LILACS, BDENF and SciELO. The ten selected studies were
      analyzed based on their level of evidence and grade of recommendation. RESULTS:
      Four categories of measures were located: antenatal perineal care, perineal
      massage during the expulsive phase of labor, manual perineal support during the
      expulsive phase of labor and perineal hyaluronidase injection. CONCLUSION: Based
      on its level of evidence, perineal massage with lubricants performed by the women
      or their partners at the end of pregnancy may be recommended as a measure
      favorable for perineal protection.

PMID- 29453138
TI  - Increased coagulation index as measured by Thromboelastography during ovarian
      stimulation for in vitro fertilization: Influence of the final oocyte maturation
      triggering agent.
AB  - OBJECTIVE: Thromboelastography (TEG) is a viscoelastic test of hemostasis which
      allows measurement of the processes of clot initiation, propagation,
      stabilization, and dissolution in real time. In this study we aimed to evaluate
      the alterations in coagulation as measured by TEG during In Vitro Fertilization
      (IVF) stimulation cycles and to investigate whether final oocyte maturation with
      recombinant hCG (rhCG) versus GnRH agonist results in a different coagulation
      state. STUDY DESIGN: This is a prospective observational study which included
      fifty-three normogonadotrophic women. All the patients received an antagonist IVF
      treatment protocol. Final oocyte maturation was triggered with either rhCG (n =
      25) or GnRH agonist (n = 26). Two patients did not complete the study due to poor
      response. Venous blood was drawn in the early and late follicular phase and on
      the day of ovum pickup. The TEG parameters assessed were R (time to first clot
      formation), K (time until the clot reaches a fixed strength), alpha angle (the
      rate of clot formation), MA (reflects maximum strength of the platelet-fibrin
      clot), LY30 (percent of clot lysis at 30 min after MA is reached) and the CI (the
      overall coagulability). RESULTS: The overall coagulation index of the entire
      study population was significantly increased on the day of ovum pickup as
      compared to the early follicular phase. This increase in the coagulation index
      was also significant in a subanalysis of patients triggered with rhCG.
      Contrarily, there was no significant increase in the coagulation index in the
      subgroup of patients triggered with GnRH agonist. CONCLUSION: Our results
      demonstrate a procoagulable state in patients after ovulation induction. Final
      triggering with GnRH agonist rather than rhCG, might lower this
      hypercoagulability pattern.

PMID- 29453140
TI  - Serum apolipoprotein A-1 concentrations and the prevalence of cardiovascular
      autonomic neuropathy in individuals with type 2 diabetes.
AB  - OBJECTIVE: To evaluate the relationship between levels of serum apolipoproteins
      and the prevalence of cardiovascular autonomic neuropathy (CAN) in type 2
      diabetes. METHODS: In total, 3199 individuals with type 2 diabetes were
      investigated in a cross-sectional study. The diagnosis of CAN was made based on
      the results of a cardiovascular reflex test. Serum apolipoprotein A-I (apoA-I)
      and apolipoprotein B (apoB) levels were measured. RESULTS: Serum apoA-1 levels
      were significantly low in individuals with CAN, but there was no significant
      association between serum apoB levels and CAN. According to the degree of
      cardiovascular autonomic dysfunction, the average apoA-I levels were
      significantly different after adjusting for other covariates (normal, 1.32 g/l,
      95% confidence interval [CI] 1.30-1.35; early, 1.29 g/l, 95% CI 1.27-1.31;
      definite, 1.27 g/l, 95% CI 1.25-1.30; P for trend = 0.010). In the multivariable
      analysis, the statistically significant association between apoA-I and CAN
      remained after adjusting for the risk factors (odds ratio per standard deviation
      increase in the log-transformed value, 0.65; 95% CI, 0.43-0.97, P = 0.036).
      Additional adjustments for serum high-sensitivity C-reactive protein (or
      fibrinogen) concentrations eliminated this relationship. CONCLUSIONS: Serum apoA
      I levels are inversely associated with the prevalence of CAN in individuals with
      type 2 diabetes. Our data also suggest that a putatively increased risk of CAN
      associated with decreased apoA-I levels might be mediated by correlated increases
      in the levels of inflammatory markers.

PMID- 29453139
TI  - Effect of inhaled corticosteroids on lung function in chronic beryllium disease.
AB  - BACKGROUND: The clinical effects of inhaled corticosteroids (ICS) on chronic
      beryllium disease (CBD) are unknown. Although frequently used for symptoms or
      disease not requiring systemic therapy, the clinical course of patients on ICS
      has not been evaluated. METHODS: In a retrospective cohort study, forty-eight
      subjects with CBD, diagnosed by granulomas on lung biopsy and treated with
      inhaled corticosteroids, were matched to sixty-eight subjects with CBD who were
      not treated. Pulmonary function testing, exercise tolerance, blood BeLPT, BAL
      cell count, and symptoms were evaluated. RESULTS: Treated patients showed no
      significant change over time in pulmonary function, when compared to controls, by
      forced vital capacity (FVC, p = 0.28) or diffusion capacity (DLCO, p = 0.45) or
      in exercise tolerance testing. However, symptoms of cough significantly improved
      in 58% (compared to 17% in controls) and dyspnea improved in 26% after ICS
      treatment (compared to 0 in controls). Symptoms of cough were improved in
      patients with a lower baseline FEV1 and FEV1/FVC ratio. Subgroup analysis showed
      significant lung function response in cases with lower baseline FEV1/FVC and
      higher residual volume (RV). CONCLUSION: Although FVC and DLCO did not improve in
      the ICS treated group, we saw no difference in decline compared to matched
      controls. Symptoms of dyspnea and cough improved with ICS especially in those
      with obstruction and air trapping suggesting that these should be considered an
      indication of ICS use in CBD patients.

PMID- 29453141
TI  - DFT/TD-DFT calculations, spectroscopic characterizations (FTIR, NMR, UV-vis),
      molecular docking and enzyme inhibition study of 7-benzoyloxycoumarin.
AB  - The quantum chemical study, spectroscopic characterization and biological
      activity of the pharmaceutically active 7-benzoyloxycoumarin (2) molecule have
      been presented. Potential energy surface (PES) scanning has been performed to
      search for the most stable molecular geometry of the present compound. The stable
      geometry in the ground state, IR, UV-Vis absorption and NMR (13C, 1H) spectra of
      the title compound were theoretically obtained and compared with the experimental
      one. Various theoretical molecular parameters like molecular energy, atomic
      charges, dipole moment, thermodynamic parameters, donor-acceptor natural bond
      orbital (NBO) hyperconjugative interaction energies, frontier molecular orbitals
      energies, HOMO-LUMO gap, molecular electrostatic potential, chemical reactivity
      descriptors, molecular polarizability and non-linear optical (NLO) properties are
      presented. Moreover, the 3D Hirshfeld surfaces and the associated 2D fingerprint
      plots have been explored. The percentages of various non-covalent interactions
      are studied and pictorialized by fingerprint plots of Hirshfeld surface. 7
      Benzoyloxycoumarin has shown promising inhibitory activity against
      butrylcholinesterase (BuChE) as compared to the reference drug, galantamine.
      Molecular docking is carried to introduce compound into the X-ray crystal
      structures of butrylcholinesterase at the active site to find out the probable
      binding mode. The results of molecular docking indicated that 7-benzoyloxy
      derivative of coumarin may show enzyme inhibitor activity.

PMID- 29453142
TI  - Impulsivity related personality traits and cigarette smoking in adults: A meta
      analysis using the UPPS-P model of impulsivity and reward sensitivity.
AB  - BACKGROUND: Although there is considerable evidence of an association between
      impulsivity and cigarette smoking, the magnitude of this association varies
      across studies. Impulsivity comprises several discrete traits that may influence
      cigarette use in different ways. The present meta-analysis aims to examine the
      direction and magnitude of relationships between specific impulsivity-related
      traits, namely lack of premeditation, lack of perseverance, sensation seeking,
      negative urgency, positive urgency and reward sensitivity and both smoking status
      and severity of nicotine dependence in adults across studies and to delineate
      differences in effects across these relationships. METHODS: Ninety-seven studies
      were meta-analysed using random-effects models to examine the relationship
      between impulsivity-related traits and smoking status and severity of nicotine
      dependence. A number of demographic and methodological variables were also
      assessed as potential moderators. RESULTS: Smoking status and severity of
      nicotine dependence were significantly associated with all impulsivity-related
      traits except reward sensitivity. Lack of premeditation and positive urgency
      showed the largest associations with smoking status (r = 0.20, r = 0.24
      respectively), while positive urgency showed the largest association with
      severity of nicotine dependence (r = 0.23). Study design moderated associations
      between lack of premeditation and lack of perseverance and smoking status, with
      larger effects found in cross-sectional compared to prospective studies.
      CONCLUSIONS: Finding suggest that impulsivity is associated with an increased
      likelihood of being a smoker and greater nicotine dependence. Specific
      impulsivity-related traits differentially relate to smoking status and severity
      of nicotine dependence. Understanding the complexity of impulsivity-related
      traits in relation to smoking can help to identify potential smokers and could
      inform cessation treatment.

PMID- 29453143
TI  - Structure and physico-mechanical properties of low temperature plasma treated
      electrospun nanofibrous scaffolds examined with atomic force microscopy.
AB  - Electrospun nanofibrous scaffolds are willingly used in tissue engineering
      applications due to their tunable mechanical, chemical and physical properties.
      Additionally, their complex openworked architecture is similar to the native
      extracellular matrix of living tissue. After implantation such scaffolds should
      provide sufficient mechanical support for cells. Moreover, it is of crucial
      importance to ensure sterility and hydrophilicity of the scaffold. For this
      purpose, a low temperature surface plasma treatment can be applied. In this
      paper, we report physico-mechanical evaluation of stiffness and adhesive
      properties of electrospun mats after their exposition to low temperature plasma.
      Complex morphological and mechanical studies performed with an atomic force
      microscope were followed by scanning electron microscope imaging and a
      wettability assessment. The results suggest that plasma treatment can be a useful
      method for the modification of the surface of polymeric scaffolds in a desirable
      manner. Plasma treatment improves wettability of the polymeric mats without
      changing their morphology.

PMID- 29453144
TI  - Polydipsia and anxiety as early warning signs of relapse in schizophrenia.

PMID- 29453145
TI  - Demographic and clinical characteristics associated with a history of bizarre
      delusions in a cross-diagnostic sample of individuals with psychotic disorders.
AB  - Bizarre delusions (BizD) are not specific to schizophrenia (SZ) and can be found
      in other psychotic disorders. However, to date, there are no studies
      investigating socio-demographic and clinical characteristics associated with BizD
      across the psychosis spectrum. In this study 819 subjects with a diagnosis of SZ
      (n = 250), schizoaffective disorder (SZA) (n = 228) and bipolar I disorder (BD)
      (n = 341) were included. Patients with history of BizD and with no BizD were
      compared with respect to socidemographic and clinical variables, and predictors
      of BizD were explored. Patients with BizD were less educated, less likely to be
      married, had higher Positive and Negative Syndrome Scale (PANSS) negative scores
      and lower Young Mania Rating Scale scores. Younger age, SZ and SZA diagnoses,
      higher PANSS positive scores, presence of reference delusions, tactile and
      olfactory hallucinations were predictors. Our results indicate that BizD are
      associated with higher illness severity, lower functionality and specific set of
      symptoms.

PMID- 29453146
TI  - Cannabis induced koro in a Nepali migrant.

PMID- 29453147
TI  - Occupational stress and productivity-A forensic perspective.

PMID- 29453148
TI  - Pattern of psychotropic drugs prescription in patients on hemodialysis: A single
      centre experience from South India.

PMID- 29453149
TI  - A case of very early neurosyphilis presented as schizophrenia-like psychosis.

PMID- 29453150
TI  - Aripiprazole induced neck dystonia and oculogyric crisis.

PMID- 29453151
TI  - Problematic shopping behavior: Prevalence and implication for screening &
      intervention in health care setting.

PMID- 29453152
TI  - Gaming disorder as a consequence of attempt at self- medication: Empirical
      support to the hypothesis.

PMID- 29453153
TI  - Expecting exoskeletons for more than spinal cord injury.

PMID- 29453155
TI  - Evaluation of the triage performed by registered nurses in the Hospital Clinico
      Universitario "Lozano Blesa" Emergency service (Saragossa, Spain).
AB  - OBJECTIVE: To evaluate nurses' triage quality and adequacy in Saragossa's
      Hospital Clinico and to compare the main characteristics of "urgent" and "non
      urgent" visits to the Hospital Emergency Department (HED). METHOD: This
      exploratory-retrospective research study was carried out over the last 3 months
      of 2015 (paediatrics, gynaecological and ophthalmologic emergencies were
      excluded). Data were obtained from the "Puesto Clinico Hospitalario" programme
      used in the HED. The quality of the triage performed by nurses was assessed using
      the 4 indexes proposed by Gomez Jimenez and the adequacy of patient
      classification was established by relating the level of triage assigned with the
      place of care, length of stay in the HED and type of discharge. Differences
      between "non-urgent" (seen in outpatient consultations of the HED) and "urgent"
      visits were analysed, RESULTS: 22,047 individuals were included. Quality indices
      relating to waiting times were not fully met. Higher severity of triage was
      associated with being attended in the area of Vital and Medical Care, a longer
      stay in the HED and a higher proportion of hospital admissions (p<.001), so that
      triage performed by nursing is considered adequate. "Non-urgent" visits obtained
      less severity of triage, a shorter stay in HED and a greater proportion of
      hospital discharges (p<.001). CONCLUSIONS: Nursing triage needs to improve
      quality aspects related to waiting times but is appropriate enough as it
      discriminates between place of care and type of discharge for each level of
      triage within the desirable limits.

PMID- 29453154
TI  - Unique pharmacology of a novel allosteric agonist/sensitizer insulin receptor
      monoclonal antibody.
AB  - OBJECTIVE: Insulin resistance is a key feature of Type 2 Diabetes (T2D), and
      improving insulin sensitivity is important for disease management. Allosteric
      modulation of the insulin receptor (IR) with monoclonal antibodies (mAbs) can
      enhance insulin sensitivity and restore glycemic control in animal models of T2D.
      METHODS: A novel human mAb, IRAB-A, was identified by phage screening using
      competition binding and surface plasmon resonance assays with the IR
      extracellular domain. Cell based assays demonstrated agonist and sensitizer
      effects of IRAB-A on IR and Akt phosphorylation, as well as glucose uptake. Lean
      and diet-induced obese mice were used to characterize single-dose in vivo
      pharmacological effects of IRAB-A; multiple-dose IRAB-A effects were tested in
      obese mice. RESULTS: In vitro studies indicate that IRAB-A exhibits sensitizer
      and agonist properties distinct from insulin on the IR and is translated to
      downstream signaling and function; IRAB-A bound specifically and allosterically
      to the IR and stabilized insulin binding. A single dose of IRAB-A given to lean
      mice rapidly reduced fed blood glucose for approximately 2 weeks, with
      concomitant reduced insulin levels suggesting improved insulin sensitivity.
      Phosphorylated IR (pIR) from skeletal muscle and liver were increased by IRAB-A;
      however, phosphorylated Akt (pAkt) levels were only elevated in skeletal muscle
      and not liver vs. control; immunochemistry analysis (IHC) confirmed the long
      lived persistence of IRAB-A in skeletal muscle and liver. Studies in diet-induced
      obese (DIO) mice with IRAB-A reduced fed blood glucose and insulinemia yet
      impaired glucose tolerance and led to protracted insulinemia during a meal
      challenge. CONCLUSION: Collectively, the data suggest IRAB-A acts allosterically
      on the insulin receptor acting non-competitively with insulin to both activate
      the receptor and enhance insulin signaling. While IRAB-A produced a decrease in
      blood glucose in lean mice, the data in DIO mice indicated an exacerbation of
      insulin resistance; these data were unexpected and suggested the interplay of
      complex unknown pharmacology. Taken together, this work suggests that IRAB-A may
      be an important tool to explore insulin receptor signaling and pharmacology.

PMID- 29453156
TI  - Approaching the experience of people through the process of a colostomy.
AB  - OBJECTIVE: The purpose of this paper is to explore the experience of people who
      go through the process of a colostomy. METHOD: Methodological approach of
      qualitative type and with a phenomenological framework, through in-depth
      interviews. Six women and 12 men, between 38 and 86 years of age, were
      interviewed before and after surgery, between 3 and 6 months after the
      intervention. The discourses were recorded and transcribed verbatim and analyzed
      following the 3 stages of Taylor and Bogdan: finding in progress, data coding and
      refinement of the understanding of the subject of study, and relativisation of
      the findings. RESULTS: Colon cancer and colostomy involve changes in a person's
      experience of privacy, and the connotations of "stigma" that can be attached to
      this vital element. It has been observed that the perception of deteriorated body
      image does not relate to an individual's gender, but rather to their age, work
      situation, type of work and social and cultural context. CONCLUSIONS: The
      reconstruction of an individual's relationship map, as a strategy for adapting to
      the process, is interrelated with social, cultural, and stoma management factors,
      and with their capacity for effective problem solving.

PMID- 29453157
TI  - [The Spanish Society of Paediatric Infectious Diseases guidelines on the
      prevention, diagnosis and treatment of neonatal herpes simplex infections].
AB  - Neonatal herpes simplex virus infections are rare, but are associated with
      significant morbidity and mortality. Most newborns acquire herpes simplex virus
      infection in the peripartum period. For peripartum transmission to occur, women
      must be shedding the virus in their genital tracts symptomatically or
      asymptomatically around the time of delivery. There are evidence-based
      interventions in pregnancy to prevent the transmission to the newborn. Caesarean
      section should be performed in the presence of herpetic lesions, and antiviral
      prophylaxis in the last weeks of pregnancy is recommended to suppress genital
      tract herpes simplex virus at the time of delivery. The diagnosis and early
      treatment of neonatal herpes simplex virus infections require a high index of
      suspicion, especially in the absence of skin lesions. It is recommended to rule
      out herpes simplex virus infections in those newborns with mucocutaneous lesions,
      central nervous system involvement, or septic appearance. The prognosis of
      newborns with skin, eye, and/or mouth disease in the high-dose acyclovir era is
      very good. Antiviral treatment not only improves mortality rates in disseminated
      and central nervous system disease, but also improves the rates of long-term
      neurodevelopmental impairment in the cases of disseminated disease.
      Interestingly, a 6-month suppressive course of oral acyclovir following the acute
      infection has improved the neurodevelopmental prognosis in patients with CNS
      involvement.

PMID- 29453158
TI  - Female perpetrated sexual offences reported to a London sexual assault referral
      centre.
AB  - A gender specific approach to understanding female sex offenders is important for
      developing prevention and treatment strategies, yet research to date is limited.
      While it is recognised that females often offend with another person, there has
      been little attempt to look beyond the two groupings of solo and co-offending and
      study females who offend in larger groups. Furthermore, very few studies have
      looked at the victims of these crimes and all of these have focussed on child
      victims only. The present work describes demographic and assault related
      characteristics of victims of all ages reporting a sexual assault by a female
      perpetrator to the Havens sexual assault referral centres in London, UK, in a
      five year period, with the aim of identifying victim, perpetrator and offence
      patterns in solo, pair and group sexual assaults. 47 cases were identified, just
      0.66% of the total cases seen, and victims ranged from 3 to 59 years of age.
      Female perpetrators actively participated in the sexual and physical violence in
      many cases and were often involved in other ways, such as facilitating the
      offence, procuring the victim and filming the assault. Victims of solo
      perpetrators were mostly children who reported an assault by a teacher or
      childminder. Victims of pairs were older and all perpetrators were male/female
      pairs, usually reportedly in a romantic relationship. Victims of groups were more
      often strangers to the perpetrators and these assaults were often very violent.
      These findings are discussed in relation to current knowledge and suggestions are
      made for further research.

PMID- 29453159
TI  - Identifying the most significant indicators of the total road safety performance
      index.
AB  - The review of the national and international literature dealing with the
      assessment of the road safety level has shown great efforts of the authors who
      tried to define the methodology for calculating the composite road safety index
      on a territory (region, state, etc.). The procedure for obtaining a road safety
      composite index of an area has been largely harmonized. The question that has not
      been fully resolved yet concerns the selection of indicators. There is a wide
      range of road safety indicators used to show a road safety situation on a
      territory. Road safety performance index (RSPI) obtained on the basis of a larger
      number of safety performance indicators (SPIs) enable decision makers to more
      precisely define the earlier goal- oriented actions. However, recording a broader
      comprehensive set of SPIs helps identify the strengths and weaknesses of a
      country's road safety system. Providing high quality national and international
      databases that would include comparable SPIs seems to be difficult since a larger
      number of countries dispose of a small number of identical indicators available
      for use. Therefore, there is a need for calculating a road safety performance
      index with a limited number of indicators (RSPIlnn) which will provide a
      comparison of a sufficient quality, of as many countries as possible. The
      application of the Data Envelopment Analysis (DEA) method and correlative
      analysis has helped to check if the RSPIlnn is likely to be of sufficient
      quality. A strong correlation between the RSPIlnn and the RSPI has been
      identified using the proposed methodology. Based on this, the most contributing
      indicators and methodologies for gradual monitoring of SPIs, have been defined
      for each country analyzed. The indicator monitoring phases in the analyzed
      countries have been defined in the following way: Phase 1- the indicators
      relating to alcohol, speed and protective systems; Phase 2- the indicators
      relating to roads and Phase 3- the indicators relating to trauma management. This
      will help achieve the standardization of indicators including data collection
      procedures and selection of the key list of indicators that need to be monitored.
      Based on the results, it has been concluded that the use of the most contributing
      indicators will make it possible to assess the level of road safety on a
      territory, with an acceptable quality score by focusing on the low-ranked
      countries. A smaller set of significant indicators defined in this manner can
      serve for a fast and simple understanding of a road safety situation and
      assessment of effects of measures undertaken. Also, this universal index approach
      is applicable in cases when a broader comprehensive set of indicators is
      analyzed, which provides a more accurate identification of weaker points and rank
      the countries in a more meaningful way.

PMID- 29453160
TI  - DNA damage and micronuclei in parthenogenetic and bisexual Darevskia rock lizards
      from the areas with different levels of soil pollution.
AB  - Natural species are widely used as indicator organisms to estimate of the impact
      of environmental pollution. Here we present the results of first study of a
      reliability of parthenogenetic Darevskia armeniaca and bisexual Darevskia raddei
      rock lizards as sentinels for monitoring of environmental genotoxicity. The comet
      assay and micronucleus test were applied to the lizards sampled in six areas in
      Armenia and Artsakh with different levels of soil contamination. The results
      obtained showed a clear relationship between the pollution level of lizards'
      habitats and the frequency of DNA damage in the comet assay. Low baseline
      frequency of micronuclei in D. armeniaca and D. raddei, however, makes this
      parameter ineffective for environmental genotoxicity evaluation. The
      parthenogenetic lizards D. armeniaca showed higher sensitivity toward genotoxic
      pollutions compared with bisexual D. raddei living in the same environment. The
      correlations between soil content of heavy metals Cr, Cu, Zn, Mo, Pb and DNA
      damage in D. armeniaca and between Cu, As, Mo, Pb and DNA damage in D. raddei
      were revealed. Overall, the lizards D. raddei and D. armeniaca appeared to be
      sensitive species in detecting soil pollution in natural environment. The
      application of the comet assay in Darevskia lizard species can be considered as a
      more appropriate method than a micronucleus test. The use of parthenogenetic
      lizards D. armeniaca as bioindicator will permit to assess the environmental
      genotoxicity independent of the genetic polymorphism of bisexual species.

PMID- 29453161
TI  - Gamma irradiation during gametogenesis in young adult zebrafish causes persistent
      genotoxicity and adverse reproductive effects.
AB  - The biological effects of gamma radiation may exert damage beyond that of the
      individual through its deleterious effects on reproductive function. Impaired
      reproductive performance can result in reduced population size over consecutive
      generations. In a continued effort to investigate reproductive and heritable
      effects of ionizing radiation, we recently demonstrated adverse effects and
      genomic instability in progeny of parents exposed to gamma radiation. In the
      present study, genotoxicity and effects on the reproduction following subchronic
      exposure during a gametogenesis cycle to 60Co gamma radiation (27 days, 8.7 and
      53 mGy/h, total doses 5.2 and 31 Gy) were investigated in the adult wild-type
      zebrafish (Danio rerio). A significant reduction in embryo production was
      observed one month after exposure in the 53 mGy/h exposure group compared to
      control and 8.7 mGy/h. One year later, embryo production was significantly lower
      in the 53 mGy/h group compared only to control, with observed sterility,
      accompanied by a regression of reproductive organs in 100% of the fish 1.5 years
      after exposure. Histopathological examinations revealed no significant changes in
      the testis in the 8.7 mGy/h group, while in 62.5% of females exposed to this dose
      rate the oogenesis was found to be only at the early previtellogenic stage. The
      DNA damage determined in whole blood, 1.5 years after irradiation, using a high
      throughput Comet assay, was significantly higher in the exposed groups (1.2 and 3
      fold increase in 8.7 and 53 mGy/h females respectively; 3-fold and 2-fold
      increase in 8.7 and 53 mGy/h males respectively) compared to controls. A
      significantly higher number of micronuclei (4-5%) was found in erythrocytes of
      both the 8.7 and 53 mGy/h fish compared to controls. This study shows that gamma
      radiation at a dose rate of >= 8.7 mGy/h during gametogenesis causes adverse
      reproductive effects and persistent genotoxicity (DNA damage and increased
      micronuclei) in adult zebrafish.

PMID- 29453162
TI  - The effect of cadmium exposure on diversity of intestinal microbial community of
      Rana chensinensis tadpoles.
AB  - Cadmium is a natural and widely distributed toxicant, and can be commonly found
      in environment. Intestinal microbiota plays a very important role in maintaining
      its host's health. The effects of cadmium on the intestinal microbiota
      composition and stability of amphibians are little known. We exposed Rana
      chensinensis (R. chensinensis) embryos to different concentrations of cadmium (0,
      112 and 448 MUg Cd L-1) until they reached Gosner stage 38, and analyzed their
      microbial communities using 16S rRNA amplicon sequencing. By measures of both
      alpha and beta diversity, intestinal microbial communities were significantly
      differentiated in 448 MUg Cd L-1 exposure groups. Cadmium exposure significantly
      altered the intestinal microflora diversity and composition of R. chensinensis.
      At the phylum level, it is worth noting that Fusobacteria and Spirochaetae were
      not detected in 448 MUg Cd L-1 exposure groups. Firmicutes rapidly decreased in
      448 MUg Cd L-1 exposure group. At the genus level, Succinispira (Firmicutes),
      Desulfovibrio (Proteobacteria) and Fusobacterium (Fusobacteria) vanished in 448
      MUg Cd L-1 exposure groups. Our results demonstrate that cadmium exposure changed
      the composition and decreased the community diversity of intestinal microbiota of
      R. chensinensis tadpoles. Our study may provide a new framework based on
      intestinal microbiota to evaluate the response of amphibians to environmental
      chemicals pollution.

PMID- 29453164
TI  - Perforated Giant Meckel Diverticulitis in an elderly patient: Case report and
      review of the literature.
AB  - INTRODUCTION: Giant Meckel's diverticula are a relatively rare form of Meckel's,
      and henceforth their natural history is not clearly defined. They're currently
      thought of as an infrequent form of ileal dysgenesis. Noted complications include
      perforation, torsion and bowel obstruction. A much rarer presentation is Giant
      Meckel's diverticulitis. CASE: A 71 year old white female presented herself to
      the Emergency Department of a small urban community hospital, complaining of
      severe abdominal pain, nausea & vomiting. Her preoperative workup was consistent
      with Giant Meckel's diverticulitis, with evidence for perforation. She was taken
      for a laparotomy, which confirmed the diagnosis, and was treated with a small
      bowel resection. She made an otherwise uncomplicated recovery. CONCLUSION: Giant
      Meckel's diverticula and their complications require a high index of suspicion
      and once diagnosed, they should be managed expeditiously to avoid complications.

PMID- 29453163
TI  - Incidentally Discovered Persistent Mullerian Duct Syndrome in a 45-year-old male
      presenting with germ cell tumor and bilateral cryptorchidism: A rare case report
      and review of the literature.
AB  - INTRODUCTION: Persistent Mullerian Duct Syndrome (PMDS) is a rare sexual disease.
      It is characterized by the presence of female reproductive structures such as
      uterus, cervix, fallopian tubes and upper part of vagina in a normal
      genotypically and phenotypically male. The diagnosis is usually incidental since
      the patients will present with normal external genitalia and secondary sexual
      characteristics. Imaging techniques such as magnetic resonance imaging (MRI),
      computed tomography (CT) scan, or ultrasound (US) could help in the diagnosis.
      CASE PRESENTATION: A 45-year-old male presented with bilateral undescended testes
      since birth and 2 months history abdominal mass. CT scan showed a 13 * 17 * 20 cm
      solid pelvi-abdominal mass. The diagnosis of mixed germ cell tumor of the
      undescended testes was made based on the CT scan. During resection of the tumor,
      patient was found to have a uterus, fallopian tubes and ovaries. DISCUSSION:
      Pathological investigation showed endometrial tissues with portion of lower
      uterine segment and cervix with remnant of testes with marked atrophy. No Ovarian
      tissues were found nor fallopian tube as well. The diagnosis of PMDS was made
      based on the pathological report. CONCLUSION: PMDS is a challenging condition to
      diagnose. Radiological investigation can miss the presence of the Mullerian duct
      structures as in our case because of the unusual presentation of this condition.
      Early diagnosis and management is important as the malignant transformation is
      high due to the undescended testes.

PMID- 29453165
TI  - Endoscopic submucosal dissection for the diagnosis and therapy of pedunculated
      gastric cancer with prolapse into the duodenal bulb: A case report.
AB  - INTRODUCTION: Preoperative diagnosis of gastric cancer invasion is not always
      sufficiently accurate. Diagnostic endoscopic submucosal dissection (ESD) can be
      performed for the purpose of accurate decision making and to avoid partial
      treatment vs aggressive over-treatment. We present a patient with the gastric
      cancer with indeterminate pre-operative diagnosis for depth of the invasion. CASE
      PRESENTATION: A 70-year-old man presented at our hospital because both anti
      Helicobacter pylori (Hp) IGG antibody and serum pepsinogen (PG) levels were
      classified as positive. Upper gastrointestinal endoscopy was performed, and a
      large (3.5 cm) pedunculated polyp-shaped gastric cancer with prolapse into the
      duodenal bulb was found. [fluorine-18]-fluorodeoxy-glucose (18F-FDG)-positron
      emission tomography (PET)/computed tomography (CT) imaging showed high 18F-FDG
      uptake, suggesting the possibility of advanced gastric cancer. Since the pre
      operative diagnosis of the cancer invasion was indeterminable, diagnostic ESD was
      performed. The pathohistological diagnosis was early gastric cancer (33 * 35 * 20
      mm, well differentiated tubular adenocarcinoma [tub1], pT1a[M], ly[--], v[--],
      UL[--], pHM0, pVM0) according to the Japanese classification of gastric
      carcinoma. DISCUSSION AND CONCLUSION: It was reported that ESD for early gastric
      cancers that met the expanded criteria was acceptable and should be the standard
      treatment instead of gastrectomy. The expanded criteria included cancer confined
      to the mucosa (cT1a), a single primary intestinal-type gastric adenocarcinoma, an
      ulcer-negative lesion of any size. We reported a case of pedunculated gastric
      cancer with prolapse into the duodenal bulb that could be treated by ESD. The
      present case is a good example of diagnostic ESD being used to minimize the
      damage of gastric cancer treatment.

PMID- 29453166
TI  - Skull metastasis revealing a renal tumor: A case report and review of the
      literature.
AB  - BACKGROUND: Renal cell carcinomas represent 85% of malignant renal tumors.
      Typically, the tumor remains asymptomatic a long time before the appearance of
      urologic clinical signs. In some cases, metastasis can precede the manifestations
      of the primary tumor. Different sites are potential metastatic localizations for
      renal tumors, including skull metastases who represent a very rare location. CASE
      DESCRIPTION: We report the case of a 65-year-old man presented after the
      appearance of a skull mass. This tumefaction developed and had progressively
      grown up during 9 months. Neurological examination was normal. Brain imaging
      showed a soft tissue lesion in the left parietal bone with marked osteolysis.
      Peroperative was found a huge oval-shape hemorrhagic and firm mass associated
      with scalp invasion and bone destruction that was totally resected.
      Histopathology revealed renal cell carcinoma (RCC). Pelvic and abdominal CT scan
      was performed, revealing a large mass on the left kidney with irregular contours
      and poor definition. The patient was then transferred to urology where he
      underwent nephrectomy. The patient went then through adjuvant chemotherapy.
      Clinical and radiological follow up of 12 months did not bring to light tumor
      recurrence. CONCLUSIONS: Although metastases to the head and neck occur
      infrequently, they should be considered when evaluating any unusual subcutaneous
      mass in the head and neck. RCC should not be discounted when sites as unlikely as
      the calvaria are evaluated. Treatment of metastatic renal cell carcinoma is
      complex, and the optimal regimen for achieving a lasting response without severe
      toxicity has not yet been defined.

PMID- 29453167
TI  - Electrochemical detection of methylated DNA on a microfluidic chip with
      nanoelectrokinetic pre-concentration.
AB  - DNA methylation is considered to be a promising marker for the early diagnosis
      and prognosis of cancer. However, direct detection of the methylated DNAs in
      clinically relevant samples is still challenging because of its extremely low
      concentration (~fM). Here, an integrated microfluidic chip is reported, which is
      capable of pre-concentrating the methylated DNAs using ion concentration
      polarization (ICP) and electrochemically detecting the pre-concentrated DNAs on a
      single chip. The proposed chip is the first demonstration of an electrochemical
      detection of both level and concentration of the methylated DNAs by integrating a
      DNA pre-concentration unit without gene amplification. Using the proposed chip,
      500 fM to 500 nM of methylated DNAs is pre-concentrated by almost 100-fold in 10
      min, resulting in a drastic improvement of the electrochemical detection
      threshold down to the fM level. The proposed chip is able to measure not only the
      DNA concentration, but also the level of methylation using human urine sample by
      performing a consecutive electrochemical sensing on a chip. For clinical
      application, the level as well as the concentration of methylation of glutathione
      S transferase-P1 (GSTP1) and EGF-containing fibulin-like extracellular matrix
      protein 1 (EFEMP1), which are known to be closely associated with prostate cancer
      diagnosis, are electrochemically detected in human urine spiked with these genes.
      The developed chip shows a limit of detection (LoD) of 7.9 pM for GSTP1 and 11.8
      pM for EFEMP1 and is able to detect the level of methylation in a wide range from
      10% to 100% with the concentration variation from 50 pM to 500 nM.

PMID- 29453168
TI  - Spatial-temporal cluster analysis of mortality from road traffic injuries using
      geographic information systems in West of Iran during 2009-2014.
AB  - INTRODUCTION: Road traffic injuries (RTIs) are considered as one of the most
      important health problems endangering people's life. The examination of the
      geographical distribution of RTIs could help policymakers in better planning to
      reduce RTIs. This study, therefore, aimed to determine the spatial-temporal
      clustering of mortality from RTIs in West of Iran. METHODS: Deaths from RTIs,
      registered in Forensic Medicine Organization of Kermanshah province over a period
      of six years (2009-2014), were used. Using negative binomial regression, the
      mortality trend was investigated. In order to investigate the spatial
      distribution of RTIs, we used ArcGIS. (Version 10.3). RESULTS: The median age of
      the 3231 people died in RTIs was 37 (IQR = 31) year, 78.4% were male. The 6-year
      average mortality rate from RTIs was 27.8/100,000 deaths, and the average rate
      had a declining trend. The dispersion of RTIs showed that most deaths occurred in
      Kermanshah, Islamabad, Bisotun, and Harsin road axes, respectively. The mean
      center of all deaths from RTIs occurred in Kermanshah province, the central area
      of Kermanshah district. The spatial trend of such deaths has moved to the
      northeast-southwest, and such deaths were geographically centralized. Results of
      Moran's I with respect to cluster analysis also indicated positive spatial
      autocorrelations. CONCLUSION: The results showed that the mortality rate from
      RTIs, despite the decline in recent years, is still high when compared with other
      countries. The clustering of accidents raises the concern that road
      infrastructure in certain locations may also be a factor. Regarding the results
      related to the temporal analysis, it is suggested that the enforcement of traffic
      rules be stricter at rush hours.

PMID- 29453169
TI  - Randomized EEG functional brain networks in major depressive disorders with
      greater resilience and lower rich-club coefficient.
AB  - OBJECTIVE: Some studies have shown that the functional electroencephalogram (EEG)
      and functional magnetic resonance imaging (fMRI) networks in those with major
      depressive disorders (MDDs) have an abnormal random topology. In this study we
      aimed to further investigate the characteristics of the randomized functional
      brain networks in MDDs by examining resting-state scalp-EEG data. METHODS: Based
      on the methods of independent component analysis (ICA) and graph theoretic
      analysis, the abnormalities in the power spectral density (PSD) functional brain
      networks were compared between 13 MDDs and 13 matched healthy controls (HCs).
      Nonparametric permutation tests were performed to explore the between-group
      differences in multiple network metrics. The Pearson correlation coefficients
      were calculated to measure the linear relationships between the clinical symptom
      and network metrics. RESULTS: Compared with the HCs, the MDDs showed significant
      randomization of global network metrics, characterized by greater global
      efficiency, but lower clustering coefficient, characteristic path length, and
      local efficiency. This randomization was also reflected in the less heterogeneous
      and less fat-tailed degree distributions in the MDDs. More importantly, the
      randomized brain networks in MDDs had greater network resilience to both random
      failure and targeted attack, which might be a protective mechanism to avoid fast
      deterioration of the integrity of MDDs' brain networks under pathological attack.
      In addition, the randomized brain networks in MDDs had a lower level of rich-club
      coefficient, suggesting that the density of connections among rich-club hubs
      became sparser. Furthermore, some of the network metrics explored in this study
      were significantly associated with the severity of depression in all
      participants. CONCLUSIONS: A replicable randomization of the brain network is
      found in MDDs. The randomization is further characterized by more homogeneous
      degree distribution, greater resilience and lower rich-club coefficient,
      reflecting the reconfiguration of the brain network caused by the reduction of
      hub nodes in MDD. SIGNIFICANCE: Our results may provide new biomarkers of brain
      network organization in MDD.

PMID- 29453170
TI  - Symmetry of cortical planning for initiating stepping in sub-acute stroke.
AB  - OBJECTIVE: This study examined motor planning for stepping when the paretic leg
      was either stepping or standing (to step with the non-paretic leg), to understand
      whether difficulty with balance and walking post-stroke could be attributed to
      poor motor planning. METHODS: Individuals with stroke performed self-initiated
      stepping. Amplitude and duration of the movement-related cortical potential
      (MRCP) was measured from Cz. Electromyography (EMG) of biceps femoris (BF) and
      rectus femoris (RF) were collected. RESULTS: There were no differences between
      legs in stepping speed, MRCP or EMG parameters. The MRCPs when stepping with the
      paretic leg and the non-paretic leg were correlated. When the paretic leg was
      stepping, the MRCP amplitude correlated with MRCP duration, indicating a longer
      planning time was accompanied by higher cognitive effort. Slow steppers had
      larger MRCP amplitudes stepping with the paretic leg and longer MRCP durations
      stepping with the non-paretic leg. CONCLUSIONS: MRCP measures suggest that motor
      planning for initiating stepping are similar regardless of which limb is
      stepping. Individuals who stepped slowly had greater MRCP amplitudes and
      durations for planning. SIGNIFICANCE: Individuals who step slowly may require
      more time and effort to plan a movement, which may compromise their safety in the
      community.

PMID- 29453171
TI  - Finger strength, individuation, and their interaction: Relationship to hand
      function and corticospinal tract injury after stroke.
AB  - OBJECTIVE: The goal of this study was to determine the relative contributions of
      finger weakness and reduced finger individuation to reduced hand function after
      stroke, and their association with corticospinal tract (CST) injury. METHODS: We
      measured individuated and synergistic maximum voluntary contractions (MVCs) of
      the index and middle fingers, in both flexion and extension, of 26 individuals
      with a chronic stroke using a robotic exoskeleton. We quantified finger strength
      and individuation, and defined a novel metric that combines them - "multifinger
      capacity". We used stepwise linear regression to identify which measure best
      predicted hand function (Box and Blocks Test, Nine Hole Peg Test) and arm
      impairment (the Upper Extremity Fugl-Meyer Test). RESULTS: Compared to metrics of
      strength or individuation, capacity survived the stepwise regression as the
      strongest predictor of hand function and arm impairment. Capacity was also most
      strongly related to presence or absence of lesion overlap with the CST.
      CONCLUSIONS: Reduced strength and individuation combine to shrink the space of
      achievable finger torques, and it is the resulting size of this space - the
      multifinger capacity - that is of elevated importance for predicting loss of hand
      function. SIGNIFICANCE: Multi-finger capacity may be an important target for
      rehabilitative hand training.

PMID- 29453172
TI  - The conversion of biomass to light olefins on Fe-modified ZSM-5 catalyst: Effect
      of pyrolysis parameters.
AB  - Light olefins are the key building blocks for the petrochemical industry. In this
      study, the effects of in-situ and ex-situ process, temperature, Fe loading,
      catalyst to feed ratio and gas flow rate on the olefins carbon yield and
      selectivity were explored. The results showed that Fe-modified ZSM-5 catalyst
      increased the olefins yield significantly, and the ex-situ process was much
      better than in-situ. With the increasing of temperature, Fe-loading amount,
      catalyst to feed ratio, and gas flow rate, the carbon yields of light olefins
      were firstly increased and further decreased. The maximum carbon yield of light
      olefins (6.98% C-mol) was obtained at the pyrolysis temperature of 600 degrees C,
      catalyst to feed ratio of 2, gas flow rate of 100ml/min, and 3wt% Fe/ZSM-5 for
      cellulose. The selectivity of C2H4 was more than 60% for all feedstock, and the
      total light olefins followed the decreasing order of cellulose, corn stalk,
      hemicelluloses and lignin.

PMID- 29453173
TI  - Land use change impacts on the amount and quality of recharge water in the loess
      tablelands of China.
AB  - Exploring how land use change (LUC) influences the amount and quality of recharge
      water is important for groundwater sustainability and land use planning. With
      loess of up to 200m in thickness and unsaturated zones up to 100m below the
      surface, the loess tablelands in China can store abundant groundwater resources.
      However, groundwater depletion and substantial LUC have been simultaneously
      observed. It is thus necessary to investigate the relationship between LUC and
      groundwater. We sampled 10-m soil profiles for three land use types (farmlands,
      apple orchards of 10 and 20years old). After measuring the chloride and nitrate
      concentration in soil pore water, the LUC effects on the amount and quality of
      recharge water quality were quantified based on the mass balance method. Results
      showed that soil moisture in aged (20-year-old) apple orchards was significantly
      reduced relative to that measured in farmlands and younger (10-year-old)
      orchards, where measured soil moistures were roughly equal. The accumulated
      nitrate-nitrogen and the depth below which nitrate is stable was smallest in
      farmlands, intermediate in 10-year-old apple orchards, and largest under 20-year
      old apple orchards. The diffuse recharge was 33.0+/-17.9mmyear-1, accounting for
      7.3+/-1.8% of mean annual precipitation under farmlands; however, the conversion
      from farmlands to 20-year-old apple orchards reduced recharge by 42%. The nitrate
      infiltrating to groundwater annually was 4.9+/-2.9kghm-2 and 4.1+/-3.1kghm-2
      under farmlands and 20-year-old apple orchards, respectively. The impacts of LUC
      over the past decades have not yet reached groundwater because of low recharge
      rates; further, the primary factor influencing groundwater quality is recharge
      rate rather than pollutant concentration. As such, the LUC from farmland to apple
      orchard has little impact on short-term groundwater recharge and quality; long
      term impact, however, may be significant.

PMID- 29453174
TI  - Antibiotic resistance along an urban river impacted by treated wastewaters.
AB  - Urban rivers are impacted ecosystems which may play an important role as
      reservoirs for antibiotic-resistant (AR) bacteria. The main objective of this
      study was to describe the prevalence of antibiotic resistance along a sewage
      polluted urban river. Seven sites along the Zenne River (Belgium) were selected
      to study the prevalence of AR Escherichia coli and freshwater bacteria over a 1
      year period. Culture-dependent methods were used to estimate E. coli and
      heterotrophic bacteria resistant to amoxicillin, sulfamethoxazole, nalidixic acid
      and tetracycline. The concentrations of these four antibiotics have been
      quantified in the studied river. The antibiotic resistance genes (ARGs), sul1,
      sul2, tetW, tetO, blaTEM and qnrS were also quantified in both particle-attached
      (PAB) and free-living (FLB) bacteria. Our results showed an effect of treated
      wastewaters release on the spread of antibiotic resistance along the river.
      Although an increase in the abundance of both AR E. coli and resistant
      heterotrophic bacteria was observed from upstream to downstream sites, the
      differences were only significant for AR E. coli. A significant positive
      regression was also found between AR E. coli and resistant heterotrophic
      bacteria. The concentration of ARGs increased from upstream to downstream sites
      for both particle-attached (PAB) and free-living bacteria (FLB). Particularly, a
      significant increase in the abundance of four among six ARGs analyzed was
      observed after crossing urban area. Although concentrations of tetracycline
      significantly correlated with tetracycline resistance genes, the antibiotic
      levels were likely too low to explain this correlation. The analysis of ARGs in
      different fractions revealed a significantly higher abundance in PAB compared to
      FLB for tetO and sul2 genes. This study demonstrated that urban activities may
      increase the spread of antibiotic resistance even in an already impacted river.

PMID- 29453175
TI  - Solubilization of polycyclic aromatic hydrocarbons (PAHs) with phenol in coking
      wastewater treatment system: Interaction and engineering significance.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are accumulated in the sludge collected
      from the coking wastewater treatment. Phenol with its efficient degradation
      observed in biological treatment promotes the solubility of PAHs in aqueous
      phase. The interaction mechanism of phenol and PAHs in aqueous and sludge phases
      was systematically studied in two full-scale engineering projects composed of
      anaerobic-oxic-oxic (A-O1-O2) and anaerobic-oxic-hydrolytic-oxic (A-O1-H-O2)
      sequences. The results showed that reasonable use of phenol facilitates
      solubilization of PAHs alleviating their emission problems. The
      DeltaPAHs/Deltaphenol mass ratio in the sludge phase of A-O1-H-O2 system (146.3)
      exceeded that in A-O1-O2 one (63.80), exhibiting a good solubilization effect on
      PAHs with their more efficient degradation in the former. The full-scale
      observations were verified in laboratory solubilization experiments using
      phenanthrene (Phen), pyrene (Pyr) and benzo[a]pyrene (Bap) as the models of 3-, 4
      and 5-ring PAHs, respectively. The binding energies of [phenol-PAHs] complexes
      were calculated using computational density functional theory showing consistency
      with the experimentally observed phenol-facilitated solubilization efficiencies
      in the row of Phen>Pyr>Bap. The results showed the fate and distribution of PAHs
      in coking wastewater treatment affected by the presence of phenol serving as a
      cost effective reagent for enhanced solubilization of PAHs from the coking
      wastewater sludge.

PMID- 29453176
TI  - Toxicological interactions induced by chronic exposure to gold nanoparticles and
      microplastics mixtures in Daphnia magna.
AB  - The effects of emerging environmental contaminants on human and environmental
      health is of high concern, especially those potentially induced by mixtures. The
      main goal of the present study was to assess the chronic effects of mixtures of
      citrate stabilized ~5 nm gold nanoparticles (AuNP) and 1-5MUm microplastics (MP)
      on Daphnia magna. A 21-day bioassay was carried out. The effect criteria were
      parental mortality, somatic growth and several reproductive parameters. AuNP
      induced parental mortality, reduced the total offspring and caused immobile
      juveniles and aborted eggs. MP induced parental mortality, delayed the first
      brood release, decreased the number of broods released, the total offspring, and
      caused immobile juveniles. All the mixtures caused higher toxicity than AuNP and
      MP alone. Based on parental mortality, evidences of antagonism between AuNP and
      MP were observed at low concentrations of both mixture components, whereas
      evidences of synergism at high concentrations were found. Chronic (21-day)
      exposure of D. magna to AuNPs, MP, and their mixtures can impair development,
      reproduction, ultimately leading to death.

PMID- 29453177
TI  - Association of dioxin exposure and reproductive hormone levels in men living near
      the Bien Hoa airbase, Vietnam.
AB  - Dioxins are endocrine-disrupting chemicals, and their effects on reproductive
      functions are well-documented. The aim of the present study was to measure the
      levels of reproductive hormones in 42 men residing near a dioxin-contaminated
      area in Vietnam. We measured levels of 17 2,3,7,8-substituted congeners of
      polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs) and four non-ortho polychlorinated biphenyls (PCBs) in blood. Levels of
      follicle-stimulating hormone, luteinizing hormone, progesterone, prolactin,
      estradiol, and total testosterone were measured in serum. Blood dioxin levels
      were elevated; the levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin was 7.3pg/g fat.
      Seven of the men had testosterone levels below 250ng/dL, and nine men had
      prolactin levels above 9.7ng/mL. Four PCDD congeners, two PCDF congeners, one PCB
      congener, and the sum TEQ of PCDDs, PCDDs/Fs, and PCDDs/Fs/PCBs were positively
      and significantly correlated with prolactin levels. Two PCDD congeners, six PCDF
      congeners, two PCB congeners, and the TEQs of PCDFs and PCBs were negatively and
      significantly correlated with testosterone levels. There were no significant
      correlations between dioxin congeners and follicle-stimulating hormone,
      luteinizing hormone, or progesterone levels.

PMID- 29453178
TI  - Seasonal dynamics of tetracycline resistance gene transport in the Sumas River
      agricultural watershed of British Columbia, Canada.
AB  - Environmental transport of contaminants that can influence the development of
      antibiotic resistance in bacteria is an important concern in the management of
      ecological and human health risks. Agricultural regions are locales where
      practices linked to food crop and livestock production can introduce contaminants
      that could alter the selective pressures for the development of antibiotic
      resistance in microbiota. This is important in regions where the use of animal
      manure or municipal biosolids as waste and/or fertilizer could influence
      selection for antibiotic resistance in pathogenic bacterial species. To
      investigate the environmental transport of contaminants that could lead to the
      development of antibiotic resistance in bacteria, a watershed with one of the
      highest levels of intensity of agricultural activity in Canada was studied; the
      Sumas River located 60 km east of Vancouver, British Columbia. This two-year
      assessment monitored four selected tetracycline resistance genes (tet(O), tet(M),
      tet(Q), tet(W)) and water quality parameters (temperature, specific conductivity,
      turbidity, suspended solids, nitrate, phosphate and chloride) at eight locations
      across the watershed. The tetracycline resistance genes (Tcr) abundances in the
      Sumas River network ranged between 1.47 * 102 and 3.49 * 104 copies/mL and ranged
      between 2.3 and 6.9 copies/mL in a control stream (located far from agricultural
      activities) for the duration of the study. Further, Tcr abundances that were
      detected in the wet season months ranged between 1.3 * 103 and 2.29 * 104
      copies/mL compared with dry season months (ranging between 0.6 and 31.2
      copies/mL). Highest transport rates between 1.67 * 1011 and 1.16 * 1012 copies/s
      were observed in November 2005 during periods of high rainfall. The study showed
      that elevated concentrations of antibiotic resistance genes in the order of 102
      104 copies/mL can move through stream networks in an agricultural watershed but
      seasonal variations strongly influenced specific transport patterns of these
      genes.

PMID- 29453179
TI  - Enhanced Cr(VI) removal from acidic solutions using biochar modified by
      Fe3O4@SiO2-NH2 particles.
AB  - Fe3O4@SiO2-NH2 magnetic particles with core-shell structure were attached on
      carboxylated biochar derived from phoenix tree leaves to synthesize a novel
      magnetic biochar for removing Cr(VI) ions from acidic solutions. FSEM, FTEM, XRD
      characterizations of the synthesized magnetic biochar revealed that the
      Fe3O4@SiO2-NH2 magnetic particles distributed uniformly on the surface or
      macrospores of carboxylated biochar by strong chemical bonding. The Cr(VI) ions
      adsorption capacity of magnetic biochar was 27.2mg.g-1, surpassing original
      carboxylated biochar (18.2mg.g-1). VSM and XPS characterizations demonstrated
      that the attached Fe3O4@SiO2-NH2 magnetic particles not only endowed biochar with
      perfect magnetic property (23emu.g-1) but also provided complexing sites for
      binding Cr(III) cations reduced from Cr(VI) anions. The Cr(VI) ions removal by
      magnetic biochar contained three steps: (1) adsorption of Cr(VI) anions by
      protonated functional groups; (2) reduction of Cr(VI) anions to Cr(III) cations
      by electron-donor groups; and (3) chelation of Cr(III) cations by amine groups.
      The adsorption recycling test showed that magnetic biochar kept 85% of its
      initial Cr(VI) adsorption capacity at the sixth cycle, and the Fe leakage under
      pH1.0 was smaller than 0.25mg.L-1. The results indicated that this novel magnetic
      biochar was applicable for the practical treatment of Cr(VI)-containing
      wastewater.

PMID- 29453180
TI  - Study of the spatial and temporal distribution of accumulated solids in an
      experimental vertical-flow constructed wetland system.
AB  - Clogging is the most serious problem in the operation of subsurface flow
      constructed wetlands (SSF CWs) and is caused by the accumulation of solids in
      substrates. Study of the solids accumulation process can provide a more accurate
      reference for the management and maintenance of SSF CWs. In this study, an
      experimental vertical-flow constructed wetland system was recreated in the lab,
      and substrates with different depth were sampled through different operation time
      to reveal the spatial and temporal distribution of accumulated solids. During the
      study, particulates mainly accumulated through adsorption along the gravel
      surface. Therefore, the matrix could still provide sufficient space for the
      particles to pass through and be intercepted or adsorbed into the system at a
      constant rate. At the end of the study, an increasing number of large particles
      had been intercepted and were accumulated in the 0-2cm layer of the matrix,
      indicating a significant decrease in the pore diameter at the top substrate
      layer. The spatial and temporal accumulation of substrate particulates during the
      study period was accurately simulated by first-order kinetics models, and the
      simulated results were in good agreement with measured values.

PMID- 29453181
TI  - Fish consumption from urban impoundments: What are the health risks associated
      with DDTs and other organochlorine pesticides in fish to township residents of a
      major inland city.
AB  - Organochlorine pesticides (OCPs) in South Africa have for the most part been
      banned, except dichlorodiphenyltrichloroethane (DDT) which is still used as
      malaria vector control. The aim of this study was to determine OCP residues in
      the aquatic fauna of one of South Africa's most populated areas, Soweto. Risk to
      human health through OCP exposure via fish consumption was investigated. Clarias
      gariepinus was chosen as bioindicator because it is an apex predator that is in
      abundance, but is also a valued food source. Dichlorodiphenyltrichloroethanes
      (DDTs), hexachlorocyclohexanes (HCHs), and chlordanes (CHLs) were detected in the
      fish tissue with the DDTs being the most prevalent at all sites. Of the three
      locations, Fleurhof, Orlando, and Lenasia, the latter location's fish had the
      highest SigmaOCP load, ranging between 81 and 1190ng/gwm. The DDTs were
      determined to be from historic use, whereas the CHL levels indicated more recent
      inputs. Although the possibility of illegal use cannot be excluded completely,
      the presence of OCPs outside of their allowed areas of use indicate that these
      compounds not only stay in the aquatic systems long term, but may be of concern
      in areas previously not considered high risk areas. The OCP residues in C.
      gariepinus from the study area pose an extremely high risk to human health when
      consumed, and has a cancer risk as high as 1 in 10. This potential problem should
      be kept in consideration when developing national health and conservation
      strategies.

PMID- 29453182
TI  - Identification of microbial species present in a pesticide dissipation process in
      biobed systems using typical substrates from southeastern Mexico as a biomixture
      at a laboratory scale.
AB  - Biobed systems are an important option to control point pollution in agricultural
      areas. Substrates used and microbial diversity present in a biomixture perform an
      essential function in pesticide dissipation. In this study, the effects of soil
      (50% of volume/volume [V/V] proportion for all biomixtures) and four soil-based
      biomixtures (miniaturized biobeds; addition of novel substrates from southeastern
      Mexico) on dissipation of high concentrations of 2,4-dichlorophenoxyacetic acid
      (2,4-D), atrazine, carbofuran, diazinon, and glyphosate and on microbial
      diversity in biomixtures were evaluated. Small residual amounts of all pesticides
      at 20 (<2%) and 41 (<1%) days were observed; however, the lowest efficiency rates
      were observed in soil. Glyphosate was the only pesticide that completely
      dissipated in soil and biomixtures. Archaea, bacteria, and fungi were identified
      in biobeds, with bacteria being the most diverse microorganisms according to the
      identified species. The presence of white-rot fungi (normally related to
      pesticide degradation in biomixtures) was observed. Effects of the pesticide type
      and of biomixtures on pesticide dissipation were significant (P<0.05); however,
      only the effect of biomixtures on microbial diversity was significant (P<0.05);
      microbial diversity and richness had a significant effect on the residual amount
      of pesticides (P<0.05). Microbial diversity in terms of phyla was directly
      related to physicochemical parameters such as organic matter, lignin, water
      holding capacity, and pH of soil and biomixtures.

PMID- 29453183
TI  - Spatial assessment of land degradation through key ecosystem services: The role
      of globally available data.
AB  - Land degradation is a serious issue especially in dry and developing countries
      leading to ecosystem services (ESS) degradation due to soil functions' depletion.
      Reliably mapping land degradation spatial distribution is therefore important for
      policy decisions. The main objectives of this paper were to infer land
      degradation through ESS assessment and compare the modelling results obtained
      using different sets of data. We modelled important physical processes (sediment
      erosion and nutrient export) and the equivalent ecosystem services (sediment and
      nutrient retention) to infer land degradation in an area in the Ethiopian Great
      Rift Valley. To model soil erosion/retention capability, and nitrogen
      export/retention capability, two datasets were used: a 'global' dataset derived
      from existing global-coverage data and a hybrid dataset where global data were
      integrated with data from local surveys. The results showed that ESS assessments
      can be used to infer land degradation and identify priority areas for
      interventions. The comparison between the modelling results of the two different
      input datasets showed that caution is necessary if only global-coverage data are
      used at a local scale. In remote and data-poor areas, an approach that integrates
      global data with targeted local sampling campaigns might be a good compromise to
      use ecosystem services in decision-making.

PMID- 29453184
TI  - Is it photosensitization or photodegradation when UV-B irradiation is combined
      with BDE-47? Evidence from the growth and reproduction changes of rotifer
      Brachionus plicatilis.
AB  - Ecotoxicological methods were applied in the present study, and the marine
      rotifer Brachionus plicatilis was used as the toxic endpoint to depict what
      occurred when 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) was combined with solar
      ultraviolet-B radiation (UV-B). B. plicatilis was exposed to three different
      combination methods of BDE-47 and UV-B at an equal toxicity ratio, including
      normal rotifer co-cultured with UV-B-irradiated BDE-47 (known as Method I), UV-B
      irradiated rotifer co-cultured with BDE-47 exposure (known as Method II) and
      normal rotifer co-cultured with the simultaneous addition of BDE-47 and UV-B
      irradiation (known as Method III). Acute and chronic experiments were preformed
      to determine the toxicity differentiation according to the growth and
      reproduction changes in the rotifer. Twenty-four-hour acute experiments showed
      that the modes of three combined methods changed from antagonism to additive, to
      synergistic with the concentration/dose increment, and the contribution rates of
      Method I and Method II to Method III were calculated by approximately 40.4% and
      59.6%, respectively. Chronic exposure to either the single stressor or the
      combination of stressors inhibited the growth and reproduction of the rotifer,
      demonstrating the inhibition of the population growth rate and the decrease in
      the larvae production. Three combined groups presented more serious damages
      compared to groups with single stress exposure, and the ascending sequence of
      toxicity was Method I<Method II<Method III. A higher bioaccumulation of BDE-47
      was found in all combined groups than BDE-47 single stress group, and
      bioconcentration factor (BCF) general ranked Method II<Method I<Method III.
      Moreover, BDE-28, photodegradation production of BDE-47, were found in groups
      preformed Method I and III. We thus speculated that the toxicity enhancement when
      BDE-47 was combined with UV-B was mainly due to photosensitization and
      photodegradation, and the photosensitization might be more noxious to the growth
      and reproduction of the rotifer.

PMID- 29453185
TI  - Air quality impacted by local pollution sources and beyond - Using a prominent
      petro-industrial complex as a study case.
AB  - The present study combines high-resolution measurements at various distances from
      a world-class gigantic petrochemical complex with model simulations to test a
      method to assess industrial emissions and their effect on local air quality. Due
      to the complexity in wind conditions which were highly seasonal, the dominant
      wind flow patterns in the coastal region of interest were classified into three
      types, namely northeast monsoonal (NEM) flows, southwest monsoonal (SEM) flows
      and local circulation (LC) based on six years of monitoring data. Sulfur dioxide
      (SO2) was chosen as an indicative pollutant for prominent industrial emissions. A
      high-density monitoring network of 12 air-quality stations distributed within a
      20-km radius surrounding the petrochemical complex provided hourly measurements
      of SO2 and wind parameters. The SO2 emissions from major industrial sources
      registered by the monitoring network were then used to validate model simulations
      and to illustrate the transport of the SO2 plumes under the three typical wind
      patterns. It was found that the coupling of observations and modeling was able to
      successfully explain the transport of the industrial plumes. Although the
      petrochemical complex was seemingly the only major source to affect local air
      quality, multiple prominent sources from afar also played a significant role in
      local air quality. As a result, we found that a more complete and balanced
      assessment of the local air quality can be achieved only after taking into
      account the wind characteristics and emission factors of a much larger spatial
      scale than the initial (20 km by 20 km) study domain.

PMID- 29453186
TI  - High intake rates of microplastics in a Western Atlantic predatory fish, and
      insights of a direct fishery effect.
AB  - Microplastic contamination was investigated in the gut contents of an
      economically important estuarine top predator, Cynoscion acoupa, according to
      spatiotemporal and ontogenetic use of a tropical estuary. Microplastic
      contamination was found in more than half of the analysed fish. Ingested
      microplastics were classified by type, colour and length with most of the
      particles consisting of filaments (<5 mm). Longer filaments were more frequently
      ingested in the upper estuary and smaller filaments in the lower estuary, as a
      result of differences in hydrodynamic forces and proximity to the probable input
      sources. The river is likely an important source of filaments to the estuary and
      filaments ingested in the upper estuary showed little sign of weathering, when
      compared with those from the lower estuary, which are subject to intense
      weathering and consequent break-up of particles to smaller sizes. Most filaments,
      of all colours, accumulated in adults of C. acoupa, which are more susceptible to
      contamination through both direct ingestion and trophic transference as they
      shift their feeding mode to piscivory. Moreover, the highest ingestion of
      filaments in adults occurred in the lower estuary, during the late rainy season,
      likely associated with the intense fishing activities in this habitat, which
      results in a greater input of filaments from fishing gear, which are mainly blue
      in colour. Overall, 44% of the ingested filaments were blue, 20% purple, 13%
      black, 10% red and 12% white. The next most common colour, the purple filaments,
      are most likely blue filaments whose colour has weathered to purple. Red
      filaments were proportionally more ingested in the lower estuary, indicating a
      coastal/oceanic source. White and black filaments were more commonly ingested in
      the inner estuary, suggesting that they have a riverine origin and/or were
      actively ingested by juveniles and sub-adults, which inhabit the inner estuary
      and have zooplankton as an important food resource.

PMID- 29453187
TI  - Quality of Web-Based Educational Interventions for Clinicians on Human
      Papillomavirus Vaccine: Content and Usability Assessment.
AB  - BACKGROUND: Human papillomavirus (HPV) vaccination rates fall far short of
      Healthy People 2020 objectives. A leading reason is that clinicians do not
      recommend the vaccine consistently and strongly to girls and boys in the age
      group recommended for vaccination. Although Web-based HPV vaccine educational
      interventions for clinicians have been created to promote vaccination
      recommendations, rigorous evaluations of these interventions have not been
      conducted. Such evaluations are important to maximize the efficacy of educational
      interventions in promoting clinician recommendations for HPV vaccination.
      OBJECTIVE: The objectives of our study were (1) to expand previous research by
      systematically identifying HPV vaccine Web-based educational interventions
      developed for clinicians and (2) to evaluate the quality of these Web-based
      educational interventions as defined by access, content, design, user evaluation,
      interactivity, and use of theory or models to create the interventions. METHODS:
      Current HPV vaccine Web-based educational interventions were identified from
      general search engines (ie, Google), continuing medical education search engines,
      health department websites, and professional organization websites. Web-based
      educational interventions were included if they were created for clinicians
      (defined as individuals qualified to deliver health care services, such as
      physicians, clinical nurses, and school nurses, to patients aged 9 to 26 years),
      delivered information about the HPV vaccine and how to increase vaccination
      rates, and provided continuing education credits. The interventions' content and
      usability were analyzed using 6 key indicators: access, content, design,
      evaluation, interactivity, and use of theory or models. RESULTS: A total of 21
      interventions were identified, out of which 7 (33%) were webinars, 7 (33%) were
      videos or lectures, and 7 (33%) were other (eg, text articles, website modules).
      Of the 21 interventions, 17 (81%) identified the purpose of the intervention, 12
      (57%) provided the date that the information had been updated (7 of these were
      updated within the last 6 months), 14 (67%) provided the participants with the
      opportunity to provide feedback on the intervention, and 5 (24%) provided an
      interactive component. None of the educational interventions explicitly stated
      that a theory or model was used to develop the intervention. CONCLUSIONS: This
      analysis demonstrates that a substantial proportion of Web-based HPV vaccine
      educational interventions has not been developed using established health
      education and design principles. Interventions designed using these principles
      may increase strong and consistent HPV vaccination recommendations by clinicians.

PMID- 29453188
TI  - Web-Based Alcohol, Smoking, and Substance Involvement Screening Test Results for
      the General Spanish Population: Cross-Sectional Study.
AB  - BACKGROUND: Information technology in health sciences could be a screening tool
      of great potential and has been shown to be effective in identifying single-drug
      users at risk. Although there are many published tests for single-drug screening,
      there is a gap for concomitant drug use screening in general population. The
      ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) website was
      launched on February 2015 in Madrid, Spain, as a tool to identify those at risk.
      OBJECTIVE: The aim of this study was to describe the use of a tool and to analyze
      profiles of drug users, their consumption patterns, and associated factors.
      METHODS: Government- and press-released launching of a Spanish-validated ASSIST
      test from the World Health Organization (WHO) was used for voluntary Web-based
      screening of people with drug-related problems. The tests completed in the first
      6 months were analyzed . RESULTS: A total of 1657 visitors of the 15,867 visits
      (1657/15,867, 10.44%) completed the whole Web-based screening over a 6-month
      period. The users had an average age of 37.4 years, and 78.87% (1307/1657)
      screened positive for at least one of the 9 drugs tested. The drugs with higher
      prevalence were tobacco (840/1657, 50.69%), alcohol (437/1657, 26.37%), cannabis
      (361/1657, 21.79%), and sedatives or hypnotics (192/1657, 11.59%).
      Polyconsumption or concomitant drug use was stated by 31.80% (527/1657) of the
      users. Male respondents had a higher risk of having alcohol problems (odds ratio,
      OR 1.55, 95% CI 1.18-2.04; P=.002) and double the risk for cannabis problems (OR
      2.07, 95% CI 1.46-2.92; P<.001). Growing age increased by 3 times the risk of
      developing alcohol problems for people aged between 45 and 65 years (OR 3.01, 95%
      CI 1.89-4.79; P<.001). CONCLUSIONS: A Web-based screening test could be useful to
      detect people at risk. The drug-related problem rates detected by the study are
      consistent with the current literature. This tool could be useful for users, who
      use information technology on a daily basis, not seeking medical attention.

PMID- 29453189
TI  - Evaluating the CARE4Carer Blended Care Intervention for Partners of Patients With
      Acquired Brain Injury: Protocol for a Randomized Controlled Trial.
AB  - BACKGROUND: Support programs for partners of patients with acquired brain injury
      are necessary since these partners experience several unfavorable consequences of
      caregiving, such as a high burden, emotional distress, and poor quality of life.
      Evidence-based support strategies that can be included in these support programs
      are psychoeducation, skill building, problem solving, and improving feelings of
      mastery. A promising approach would seem to be to combine web-based support with
      face-to-face consultations, creating a blended care intervention. OBJECTIVE: This
      paper outlines the protocol of a randomized controlled trial to evaluate the
      CARE4Carer blended care intervention for partners of patients with acquired brain
      injury. METHODS: A multicenter two-arm randomized controlled trial will be
      conducted. A total of 120 partners of patients with acquired brain injury will be
      recruited from five rehabilitation centers in the Netherlands. The blended care
      intervention consists of a nine-session web-based support program and two face-to
      face consultations with a social worker. Themes that will be addressed are:
      giving partners insight into their own situation, including possible pitfalls and
      strengths, learning how to cope with the situation, getting a grip on thoughts
      and feelings, finding a better balance in the care for the patient with acquired
      brain injury, thinking about other possible care options, taking care of oneself,
      and communication. The intervention lasts 20 weeks and the control group will
      receive usual care. The outcome measures will be assessed at baseline and at 24-
      and 40-week follow-up. The primary outcome is caregiver mastery. Secondary
      outcome measures are strain, burden, family functioning, emotional functioning,
      coping, quality of life, participation, and social network. RESULTS: The effect
      of the intervention on the primary and secondary outcome measures will be
      determined. Additional a process evaluation will be conducted. CONCLUSIONS: The
      findings of this study will be used to improve the care for partners of patients
      with acquired brain injury. Barriers and facilitators that emerge from the
      process evaluation will be used in the nationwide implementation of the
      intervention. TRIAL REGISTRATION: Dutch Trial Register NTR6197;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6197 (Archived by
      WebCite at http://www.webcitation.org/6xHBAxx0y).

PMID- 29453190
TI  - Testing Behavior Change Techniques to Encourage Primary Care Physicians to Access
      Cancer Screening Audit and Feedback Reports: Protocol for a Factorial Randomized
      Experiment of Email Content.
AB  - BACKGROUND: Cancer Care Ontario's Screening Activity Report (SAR) is an online
      audit and feedback tool designed to help primary care physicians in Ontario,
      Canada, identify patients who are overdue for cancer screening or have abnormal
      results requiring follow-up. Use of the SAR is associated with increased
      screening rates. To encourage SAR use, Cancer Care Ontario sends monthly emails
      to registered primary care physicians announcing that updated data are available.
      However, analytics reveal that 50% of email recipients do not open the email and
      less than 7% click the embedded link to log in to their report. OBJECTIVE: The
      goal of the study is to determine whether rewritten emails result in increased
      log-ins. This manuscript describes how different user- and theory-informed
      messages intended to improve the impact of the monthly emails will be
      experimentally tested and how a process evaluation will explore why and how any
      effects observed were (or were not) achieved. METHODS: A user-centered approach
      was used to rewrite the content of the monthly email, including messages
      operationalizing 3 behavior change techniques: anticipated regret, material
      incentive (behavior), and problem solving. A pragmatic, 2x2x2 factorial
      experiment within a multiphase optimization strategy will test the redesigned
      emails with an embedded qualitative process evaluation to understand how and why
      the emails may or may not have worked. Trial outcomes will be ascertained using
      routinely collected administrative data. Physicians will be recruited for
      semistructured interviews using convenience and snowball sampling. RESULTS: As of
      April 2017, 5576 primary care physicians across the province of Ontario, Canada,
      had voluntarily registered for the SAR, and in so doing, signed up to receive the
      monthly email updates. From May to August 2017 participants received the
      redesigned monthly emails with content specific to their allocated experimental
      condition prompting use of the SAR. We have not yet begun analyses. CONCLUSIONS:
      This study will inform how to communicate effectively with primary care providers
      by email and identify which behavior change techniques tested are most effective
      at encouraging engagement with an audit and feedback report. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT03124316; https://clinicaltrials.gov/ct2/show/NCT03124316
      (Archived by WebCite at http://www.webcitation.org/6w2MqDWGu).

PMID- 29453191
TI  - A Text Message Intervention with Adaptive Goal Support to Reduce Alcohol
      Consumption Among Non-Treatment-Seeking Young Adults: Non-Randomized Clinical
      Trial with Voluntary Length of Enrollment.
AB  - BACKGROUND: Stand-alone text message-based interventions can reduce binge
      drinking episodes (>=4 drinks for women and >=5 drinks for men) among
      nontreatment-seeking young adults, but may not be optimized. Adaptive text
      message support could enhance effectiveness by assisting context-specific goal
      setting and striving, but it remains unknown how to best integrate it into text
      message interventions. OBJECTIVE: The objective of this study was to evaluate
      young adults' engagement with a text message intervention, Texting to Reduce
      Alcohol Consumption 2 (TRAC2), which focuses on reducing weekend alcohol
      consumption. TRAC2 incorporated preweekend drinking-limit goal-commitment
      ecological momentary assessments (EMA) tailored to past 2-week alcohol
      consumption, intraweekend goal reminders, self-efficacy EMA with support tailored
      to goal confidence, and maximum weekend alcohol consumption EMA with drinking
      limit goal feedback. METHODS: We enrolled 38 nontreatment-seeking young adults
      (aged 18 to 25 years) who screened positive for hazardous drinking in an urban
      emergency department. Following a 2-week text message assessment-only run-in,
      subjects were given the opportunity to enroll in 4-week intervention blocks. We
      examined patterns of EMA responses and voluntary re-enrollment. We then examined
      how goal commitment and goal self-efficacy related to event-level alcohol
      consumption. Finally, we examined the association of length of TRAC2 exposure
      with alcohol-related outcomes from baseline to 3-month follow-up. RESULTS: Among
      a diverse sample of young adults (56% [28/50] female, 54% [27/50] black, 32%
      [12/50] college enrolled), response rates to EMA queries were, on average, 82%
      for the first 4-week intervention block, 75% for the second 4-week block, and 73%
      for the third 4-week block. In the first 4 weeks of the intervention, drinking
      limit goal commitment was made 68/71 times it was prompted (96%). The percentage
      of subjects being prompted to commit to a drinking limit goal above the binge
      threshold was 52% (15/29) in week 1 and decreased to 0% (0/15) by week 4.
      Subjects met their goal 130/146 of the times a goal was committed to (89.0%).
      There were lower rates of goal success when subjects reported lower confidence
      (score <4) in meeting the goal (76% [32/42 weekends]) compared with that when
      subjects reported high confidence (98% [56/57 weekends]; P=.001). There were
      reductions in alcohol consumption from baseline to 3 months, but reductions were
      not different by length of intervention exposure. CONCLUSIONS: Preliminary
      evidence suggests that nontreatment-seeking young adults will engage with a text
      message intervention incorporating self-regulation support features, resulting in
      high rates of weekend drinking limit goal commitment and goal success.

PMID- 29453193
TI  - Risks of reformulation: French patients complain after Merck modifies
      levothyroxine pills.

PMID- 29453192
TI  - Dutch to start presumed consent for organ donation in 2020.

PMID- 29453194
TI  - Comparison of Generic Fluorescent Markers for Detection of Extracellular Vesicles
      by Flow Cytometry.
AB  - BACKGROUND: Extracellular vesicles (EVs) in biofluids are potential biomarkers of
      disease. To explore the clinical relevance of EVs, a specific generic EV marker
      would be useful, one that does not require antibodies and binds to all EVs. Here
      we evaluated 5 commonly used generic markers for flow cytometry. METHODS: Flow
      cytometry (A60-Micro, Apogee) was used to evaluate the ability of the generic EV
      markers calcein acetoxymethyl ester, calcein acetoxymethyl ester violet,
      carboxyfluorescein succinimidyl ester (CFSE), 4-(2-[6-(dioctylamino)-2
      naphthalenyl]ethenyl)-1-(3-sulfopropyl)pyridinium (di-8-ANEPPS), and lactadherin
      to stain EVs from MCF7 human breast adenocarcinoma cell line-conditioned culture
      medium [epithelial cell adhesion molecule positive (EpCAM+)] or platelet EVs from
      human plasma [integrin beta3 positive (CD61+)]. Side scatter triggering was
      applied as a reference, and the influence of non-EV components (proteins and
      lipoproteins) was evaluated. RESULTS: Di-8-ANEPPS, lactadherin, and side scatter
      detected 100% of EpCAM+ MCF7 EVs. Lactadherin and side scatter detected 33% and
      61% of CD61+ EVs, respectively. Di-8-ANEPPS detected platelet EVs only if soluble
      protein was first removed. Because all generic markers stained proteins, at best
      33% of platelet EVs in plasma were detected. The calcein markers and CFSE were
      either insensitive to EVs in both samples or associated with swarm detection.
      CONCLUSIONS: None of the generic markers detected all and only EVs in plasma.
      Side scatter triggering detected the highest concentration of plasma EVs on our
      A60-Micro, followed by lactadherin. The choice between scatter or lactadherin
      primarily depends on the analytical sensitivity of the flow cytometer used.

PMID- 29453195
TI  - Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal
      dominant non-syndromic hearing loss.
AB  - Background Hereditary sensorineural hearing loss is a genetically heterogeneous
      disorder. Objectives This study was designed to explore the genetic etiology of
      deafness in a large Chinese family with autosomal dominant, nonsyndromic,
      progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing
      and linkage analysis were performed to identify pathogenic mutation. Inner ear
      expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1
      Morpholino knockdown Zebrafish were constructed to explore the deafness
      mechanism. Results We identified a cosegregating heterozygous missense mutation,
      c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) 
      a protein that functions in the Jak/ STAT pathway- are associated with ADNSHL
      Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and
      non-inflation of the swim bladder in late-stage zebrafish, which can be reversed
      by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish
      causes significant upregulation of cytokine receptor family member b4
      (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3
      pathway at the mRNA level. ConclusionIFNLR1 function is required in the auditory
      system and that IFNLR1 mutations are associated with ADNSHL. To the best of our
      knowledge, this is the first study implicating an interferon lambda receptor in
      auditory function.

PMID- 29453196
TI  - Genome-wide association study identifies ERBB4 on 2q34 as a novel locus
      associated with sperm motility in Japanese men.
AB  - BACKGROUND: The decrease in sperm motility has a potent influence on
      fertilisation. Sperm motility, represented as the percentage of motile sperm in
      ejaculated sperms, is influenced by lifestyle habits or environmental factors and
      by inherited factors. However, genetic factors contributing to individual
      differences in sperm motility remain unclear. To identify genetic factors that
      influence human sperm motility, we performed a genome-wide association study
      (GWAS) of sperm motility. METHODS: A two-stage GWAS was conducted using 811
      Japanese men in a discovery stage, followed by a replication study using an
      additional 779 Japanese men. RESULTS: In the two-staged GWAS, a single nucleotide
      polymorphism rs3791686 in the intron of gene for erb-b2 receptor tyrosine kinase
      4 (ERBB4) on chromosome 2q34 was identified as a novel locus for sperm motility,
      as evident from the discovery and replication results using meta-analysis (beta=
      4.01, combined P=5.40*10-9). CONCLUSIONS: Together with the previous evidence
      that Sertoli cell-specific Erbb4-knockout mice display an impaired ability to
      produce motile sperm, this finding provides the first genetic evidence for
      further investigation of the genome-wide significant association at the ERBB4
      locus in larger studies across diverse human populations.

PMID- 29453197
TI  - Paediatric hospital admission processes and outcomes: a qualitative study of
      parents' experiences and priorities.
AB  - BACKGROUND: Hospital admission, like hospital discharge, represents a transition
      of care associated with changes in setting, healthcare providers and clinical
      management. While considerable efforts have focused on improving the quality and
      safety of hospital-to-home transitions, there has been little focus on
      transitions into hospital. OBJECTIVES: Among children hospitalised with
      ambulatory care sensitive conditions, we aimed to characterise families'
      experiences as they transitioned from outpatient to inpatient care, identify
      hospital admission processes and outcomes most important to families and
      determine how parental perspectives differed between children admitted directly
      and through emergency departments (ED). METHODS: We conducted semistructured
      interviews with parents of hospitalised children at four structurally diverse
      hospitals. We inquired about preadmission healthcare encounters, how hospital
      admission decisions were made and parents' preferences regarding hospital
      admission processes and outcomes. Interviews were transcribed verbatim and
      analysed using a general inductive approach. RESULTS: We conducted 48 interviews.
      Participants were predominantly mothers (74%); 45% had children with chronic
      illnesses and 52% were admitted directly. Children had a median of two (IQR 1-3)
      healthcare encounters in the week preceding hospital admission, with 44% seeking
      care in multiple settings. Patterns of healthcare utilisation were influenced by
      (1) disease acuity and healthcare access; (2) past experiences; and (3) varied
      perspectives about primary care and ED roles as hospital gatekeepers.
      Participants' hospital admission priorities included: (1) effective clinical
      care; (2) efficient admission processes; (3) safety and security; (4) timeliness;
      and (5) patient and family-centred processes of care. CONCLUSIONS: Families
      received preadmission care in several settings and described varying degrees of
      care coordination during their admission processes. This research can guide
      improvements in hospitals' admission systems, necessary to achieve health system
      integration and continuity of care.

PMID- 29453198
TI  - Targeting KCa1.1 Channels with a Scorpion Venom Peptide for the Therapy of Rat
      Models of Rheumatoid Arthritis.
AB  - Fibroblast-like synoviocytes (FLSs) are a key cell type involved in rheumatoid
      arthritis (RA) progression. We previously identified the KCa1.1 potassium channel
      (Maxi-K, BK, Slo 1, KCNMA1) as a regulator of FLSs and found that KCa1.1
      inhibition reduces disease severity in RA animal models. However, systemic KCa1.1
      block causes multiple side effects. In this study, we aimed to determine whether
      the KCa1.1 beta1-3-specific venom peptide blocker iberiotoxin (IbTX) reduces
      disease severity in animal models of RA without inducing major side effects. We
      used immunohistochemistry to identify IbTX-sensitive KCa1.1 subunits in joints of
      rats with a model of RA. Patch-clamp and functional assays were used to determine
      whether IbTX can regulate FLSs through targeting KCa1.1. We then tested the
      efficacy of IbTX in ameliorating disease in two rat models of RA. Finally, we
      determined whether IbTX causes side effects including incontinence or tremors in
      rats, compared with those treated with the small-molecule KCa1.1 blocker
      paxilline. IbTX-sensitive subunits of KCa1.1 were expressed by FLSs in joints of
      rats with experimental arthritis. IbTX inhibited KCa1.1 channels expressed by
      FLSs from patients with RA and by FLSs from rat models of RA and reduced FLS
      invasiveness. IbTX significantly reduced disease severity in two rat models of
      RA. Unlike paxilline, IbTX did not induce tremors or incontinence in rats.
      Overall, IbTX inhibited KCa1.1 channels on FLSs and treated rat models of RA
      without inducing side effects associated with nonspecific KCa1.1 blockade and
      could become the basis for the development of a new treatment of RA.

PMID- 29453199
TI  - Simultaneous Assessment of Clearance, Metabolism, Induction, and Drug-Drug
      Interaction Potential Using a Long-Term In Vitro Liver Model for a Novel
      Hepatitis B Virus Inhibitor.
AB  - Long-term in vitro liver models are now widely explored for human hepatic
      metabolic clearance prediction, enzyme phenotyping, cross-species metabolism,
      comparison of low clearance drugs, and induction studies. Here, we present
      studies using a long-term liver model, which show how metabolism and active
      transport, drug-drug interactions, and enzyme induction in healthy and diseased
      states, such as hepatitis B virus (HBV) infection, may be assessed in a single
      test system to enable effective data integration for physiologically based
      pharmacokinetic (PBPK) modeling. The approach is exemplified in the case of (3S)
      4-[[(4R)-4-(2-Chloro-4-fluorophenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1,4
      dihydropyrimidin-6-yl]methyl]morpholine-3-carboxylic acid RO6889678, a novel
      inhibitor of HBV with a complex absorption, distribution, metabolism, and
      excretion (ADME) profile. RO6889678 showed an intracellular enrichment of 78-fold
      in hepatocytes, with an apparent intrinsic clearance of 5.2 ul/min per mg protein
      and uptake and biliary clearances of 2.6 and 1.6 ul/min per mg protein,
      respectively. When apparent intrinsic clearance was incorporated into a PBPK
      model, the simulated oral human profiles were in good agreement with observed
      data at low doses but were underestimated at high doses due to unexpected
      overproportional increases in exposure with dose. In addition, the induction
      potential of RO6889678 on cytochrome P450 (P450) enzymes and transporters at
      steady state was assessed and cotreatment with ritonavir revealed a complex drug
      drug interaction with concurrent P450 inhibition and moderate UDP
      glucuronosyltransferase induction. Furthermore, we report on the first evaluation
      of in vitro pharmacokinetics studies using HBV-infected HepatoPac cocultures.
      Thus, long-term liver models have great potential as translational research tools
      exploring pharmacokinetics of novel drugs in vitro in health and disease.

PMID- 29453200
TI  - Risk of Cardiovascular Disease and Death in Individuals With Prediabetes Defined
      by Different Criteria: The Whitehall II Study.
AB  - OBJECTIVE: We compared the risk of cardiovascular disease (CVD) and all-cause
      mortality in subgroups of prediabetes defined by fasting plasma glucose (FPG), 2
      h plasma glucose (2hPG), or HbA1c. RESEARCH DESIGN AND METHODS: In the Whitehall
      II cohort, 5,427 participants aged 50-79 years and without diabetes were followed
      for a median of 11.5 years. A total of 628 (11.6%) had prediabetes by the World
      Health Organization (WHO)/International Expert Committee (IEC) criteria (FPG 6.1
      6.9 mmol/L and/or HbA1c 6.0-6.4%), and 1,996 (36.8%) by the American Diabetes
      Association (ADA) criteria (FPG 5.6-6.9 mmol/L and/or HbA1c 5.7-6.4%). In a
      subset of 4,730 individuals with additional measures of 2hPG, 663 (14.0%) had
      prediabetes by 2hPG. Incidence rates of a major event (nonfatal/fatal CVD or all
      cause mortality) were compared for different definitions of prediabetes, with
      adjustment for relevant confounders. RESULTS: Compared with that for
      normoglycemia, incidence rate in the context of prediabetes was 54% higher with
      the WHO/IEC definition and 37% higher with the ADA definition (P < 0.001) but
      declining to 17% and 12% after confounder adjustment (P >= 0.111). Prediabetes by
      HbA1c was associated with a doubling in incidence rate for both the IEC and ADA
      criteria. However, upon adjustment, excess risk was reduced to 13% and 17% (P >=
      0.055), respectively. Prediabetes by FPG or 2hPG was not associated with an
      excess risk in the adjusted analysis. CONCLUSIONS: Prediabetes defined by HbA1c
      was associated with a worse prognosis than prediabetes defined by FPG or 2hPG.
      However, the excess risk among individuals with prediabetes is mainly explained
      by the clustering of other cardiometabolic risk factors associated with
      hyperglycemia.

PMID- 29453201
TI  - Hypercalcemia associated with cosmetic injections: a systematic review.
AB  - INTRODUCTION: Cosmetic injections with silicone and polymethylmethacrylate are
      not FDA approved for augmentation of body parts such as breast, buttock or legs,
      but they have been widely used for decades. Cosmetic injections can cause foreign
      body granulomas and occasionally severe and life-threatening hypercalcemia. We
      aimed to systematically analyze the published literature on cosmetic injection
      associated hypercalcemia. METHODS: We searched relevant articles on hypercalcemia
      associated with various cosmetic injections and extracted relevant data on
      demographics, cosmetic injections used, severity of hypercalcemia, management and
      outcomes. RESULTS: We identified 23 eligible patients from 20 articles. Mean age
      was 49.83 +/- 14.70 years with a female preponderance (78.26% including
      transgender females). Silicone was most commonly used, followed by
      polymethylmethacrylate and paraffin oil (43.48, 30.43, and 8.70% respectively).
      The buttock was the most common site followed by the breast (69.57% and 39.13%
      respectively). Hypercalcemia developed at mean duration of 7.96 +/- 7.19 years
      from the initial procedure. Mean ionized calcium at presentation was 2.19 +/-
      0.61 mmol/L and mean corrected calcium at presentation was 3.43 +/- 0.31 mmol/L.
      1,25-Dihydroxyvitamin D (1,25(OH)2D or calcitriol) was elevated while 25
      hydroxyvitamin D (25(OH)D) and PTH were low in majority of cases. Hypercalcemia
      was managed conservatively with hydration, corticosteroids and bisphosphonates in
      majority of cases. Surgery was attempted in 2 cases but was unsuccessful. Renal
      failure was the most common complication (82.35% cases) and 2 patients died.
      CONCLUSION: Hypercalcemia from cosmetic injections can be severe and life
      threatening and can present years after the initial procedure. Cosmetic injection
      associated granuloma should be considered a cause of hypercalcemia, especially in
      middle-aged females presenting with non-PTH-mediated, non-malignant
      hypercalcemia, which is often associated with elevated calcitriol; however, it
      should be noted that calcitriol level may be normal as well.

PMID- 29453202
TI  - MANAGEMENT OF ENDOCRINE DISEASE Hyperandrogenic states in women: pitfalls in
      laboratory diagnosis.
AB  - Measuring total testosterone level is the first-line approach in assessing
      androgen excess in women. The main pitfalls in measuring testosterone relate to
      its low concentration and to the structural similarity between circulating
      androgens and testosterone, requiring accurate techniques with high specificity
      and sensitivity. These goals can be achieved by immunoassay using a specific anti
      testosterone monoclonal antibody, ideally after an extraction step. Liquid
      chromatography coupled to tandem mass spectrometry (LC-MS/MS) will be commonly
      used for measuring testosterone, providing optimal accuracy with a low limit of
      detection. Yet, the pitfalls of these two techniques are well identified and must
      be recognized and systematically addressed. In general, laboratories using direct
      testosterone immunoassay and mass spectrometry need to operate within a quality
      framework and be actively engaged in external quality control processes and
      standardization, so as to ensure appropriate interpretation irrespective of the
      particular laboratory. Circulating testosterone is strongly bound to sex-hormone
      binding globulin (SHBG), and SHBG levels are typically low in overweight
      hyperandrogenic patients. Thus, low SHBG may decrease circulating testosterone to
      normal values, which will mask androgen excess status. One way to avoid this
      pitfall, awaiting direct free testosterone assays that are yet to be developed,
      is to measure SHBG and calculate free testosterone. A few other pitfalls will be
      discussed in this review, including those of adrenal androgen exploration, with
      the aim of helping clinicians to better handle laboratory investigation of
      androgen excess disorders in women.

PMID- 29453204
TI  - Circulating miRNA Profiles Associated With Hyperglycemia in Patients With Type 1
      Diabetes.
AB  - We investigated plasma microRNA (miRNA) profiles associated with variation of
      hyperglycemia, measured as hemoglobin A1c (HbA1c), in two panels of patients with
      type 1 diabetes (T1D). Using the HTG Molecular Diagnostics EdgeSeq platform,
      2,083 miRNAs were measured in plasma from 71 patients included in a screening
      panel. Quantitative real-time PCR was used to measure the candidate miRNAs in
      plasma from 95 patients included in an independent replication panel. We found 10
      miRNAs replicated in both panels and 4 with high statistical significance. The
      strongest positive correlations with HbA1c were found with miR-125b-5p (rs =
      0.40, P = 6.0 * 10-5) and miR-365a-3p (rs = 0.35, P = 5.9 * 10-4). The strongest
      negative correlations were found with miR-5190 (rs = -0.30, P = 0.003) and miR
      770-5p (rs = -0.27, P = 0.008). Pathway analysis revealed that 50 Kyoto
      Encyclopedia of Genes and Genomes pathways were significantly enriched by genes
      targeted by these four miRNAs. The axon guidance signaling pathway was enriched
      (P < 1 * 10-7) by genes targeted by all four miRNAs. In addition, three other
      pathways (Rap1 signaling, focal adhesion, and neurotrophin signaling) were also
      significantly enriched but with genes targeted by only by three of the identified
      miRNAs. In conclusion, our study identified four circulating miRNAs that were
      influenced by variation in hyperglycemia. Dysregulation of these miRNAs, which
      are associated with hyperglycemia in patients with T1D, may contribute to the
      development of diabetes complications. However, there are multitudes of possible
      mechanisms/pathways through which dysregulation of these miRNAs may impact risk
      of diabetes complications.

PMID- 29453206
TI  - Elevation of Hippocampal Neurogenesis Induces a Temporally Graded Pattern of
      Forgetting of Contextual Fear Memories.
AB  - Throughout life neurons are continuously generated in the subgranular zone of the
      hippocampus. The subsequent integration of newly generated neurons alters
      patterns of dentate gyrus input and output connectivity, potentially rendering
      memories already stored in those circuits harder to access. Consistent with this
      prediction, we previously showed that increasing hippocampal neurogenesis after
      training induces forgetting of hippocampus-dependent memories, including
      contextual fear memory. However, the brain regions supporting contextual fear
      memories change with time, and this time-dependent memory reorganization might
      regulate the sensitivity of contextual fear memories to fluctuations in
      hippocampal neurogenesis. By virally expressing the inhibitory designer receptor
      exclusively activated by designer drugs, hM4Di, we first confirmed that
      chemogenetic inhibition of dorsal hippocampal neurons impairs retrieval of recent
      (day-old) but not remote (month-old) contextual fear memories in male mice. We
      then contrasted the effects of increasing hippocampal neurogenesis at recent
      versus remote time points after contextual fear conditioning in male and female
      mice. Increasing hippocampal neurogenesis immediately following training reduced
      conditioned freezing when mice were replaced in the context 1 month later. In
      contrast, when hippocampal neurogenesis was increased time points remote to
      training, conditioned freezing levels were unaltered when mice were subsequently
      tested. These temporally graded forgetting effects were observed using both
      environmental and genetic interventions to increase hippocampal neurogenesis. Our
      experiments identify memory age as a boundary condition for neurogenesis-mediated
      forgetting and suggest that, as contextual fear memories mature, they become less
      sensitive to changes in hippocampal neurogenesis levels because they no longer
      depend on the hippocampus for their expression.SIGNIFICANCE STATEMENT New neurons
      are generated in the hippocampus throughout life. As they integrate into the
      hippocampus, they remodel neural circuitry, potentially making information stored
      in those circuits harder to access. Consistent with this, increasing hippocampal
      neurogenesis after learning induces forgetting of the learnt information. The
      current study in mice asks whether these forgetting effects depend on the age of
      the memory. We found that post-training increases in hippocampal neurogenesis
      only impacted recently acquired, and not remotely acquired, hippocampal memories.
      These experiments identify memory age as a boundary condition for neurogenesis
      mediated forgetting, and suggest remote memories are less sensitive to changes in
      hippocampal neurogenesis levels because they no longer depend critically on the
      hippocampus for their expression.

PMID- 29453205
TI  - Codeficiency of Lysosomal Mucolipins 3 and 1 in Cochlear Hair Cells Diminishes
      Outer Hair Cell Longevity and Accelerates Age-Related Hearing Loss.
AB  - Acquired hearing loss is the predominant neurodegenerative condition associated
      with aging in humans. Although mutations on several genes are known to cause
      congenital deafness in newborns, few genes have been implicated in age-related
      hearing loss (ARHL), perhaps because its cause is likely polygenic. Here, we
      generated mice lacking lysosomal calcium channel mucolipins 3 and 1 and
      discovered that both male and female mice suffered a polygenic form of hearing
      loss. Whereas mucolipin 1 is ubiquitously expressed in all cells, mucolipin 3 is
      expressed in a small subset of cochlear cells, hair cells (HCs) and marginal
      cells of the stria vascularis, and very few other cell types. Mice lacking both
      mucolipins 3 and 1, but not either one alone, experienced hearing loss as early
      as at 1 month of age. The severity of hearing impairment progressed from high to
      low frequencies and increased with age. Early onset of ARHL in these mice was
      accompanied by outer HC (OHC) loss. Adult mice conditionally lacking mucolipins
      in HCs exhibited comparable auditory phenotypes, thereby revealing that the
      reason for OHC loss is mucolipin codeficiency in the HCs and not in the stria
      vascularis. Furthermore, we observed that OHCs lacking mucolipins contained
      abnormally enlarged lysosomes aggregated at the apical region of the cell,
      whereas other organelles appeared normal. We also demonstrated that these
      aberrant lysosomes in OHCs lost their membrane integrity through lysosomal
      membrane permeabilization, a known cause of cellular toxicity that explains why
      and how OHCs die, leading to premature ARHL.SIGNIFICANCE STATEMENT Presbycusis,
      or age-related hearing loss (ARHL), is a common characteristic of aging in
      mammals. Although many genes have been identified to cause deafness from birth in
      both humans and mice, only a few are known to associate with progressive ARHL,
      the most prevalent form of deafness. We have found that mice lacking two
      lysosomal channels, mucolipins 3 and 1, suffer accelerated ARHL due to auditory
      outer hair cell degeneration, the most common cause of hearing loss and
      neurodegenerative condition in humans. Lysosomes lacking mucolipins undergo
      organelle membrane permeabilization and promote cytotoxicity with age, revealing
      a novel mechanism of outer hair cell degeneration and ARHL. These results
      underscore the importance of lysosomes in hair cell survival and the maintenance
      of hearing.

PMID- 29453207
TI  - Hippocampal Ripple Oscillations and Inhibition-First Network Models: Frequency
      Dynamics and Response to GABA Modulators.
AB  - Hippocampal ripples are involved in memory consolidation, but the mechanisms
      underlying their generation remain unclear. Models relying on interneuron
      networks in the CA1 region disagree on the predominant source of excitation to
      interneurons: either "direct," via the Schaffer collaterals that provide
      feedforward input from CA3 to CA1, or "indirect," via the local pyramidal cells
      in CA1, which are embedded in a recurrent excitatory-inhibitory network. Here, we
      used physiologically constrained computational models of basket-cell networks to
      investigate how they respond to different conditions of transient, noisy
      excitation. We found that direct excitation of interneurons could evoke ripples
      (140-220 Hz) that exhibited intraripple frequency accommodation and were
      frequency-insensitive to GABA modulators, as previously shown in in vitro
      experiments. In addition, the indirect excitation of the basket-cell network
      enabled the expression of intraripple frequency accommodation in the fast-gamma
      range (90-140 Hz), as in vivo In our model, intraripple frequency accommodation
      results from a hysteresis phenomenon in which the frequency responds
      differentially to the rising and descending phases of the transient excitation.
      Such a phenomenon predicts a maximum oscillation frequency occurring several
      milliseconds before the peak of excitation. We confirmed this prediction for
      ripples in brain slices from male mice. These results suggest that ripple and
      fast-gamma episodes are produced by the same interneuron network that is
      recruited via different excitatory input pathways, which could be supported by
      the previously reported intralaminar connectivity bias between basket cells and
      functionally distinct subpopulations of pyramidal cells in CA1. Together, our
      findings unify competing inhibition-first models of rhythm generation in the
      hippocampus.SIGNIFICANCE STATEMENT The hippocampus is a part of the brain of
      humans and other mammals that is critical for the acquisition and consolidation
      of memories. During deep sleep and resting periods, the hippocampus generates
      high-frequency (~200 Hz) oscillations called ripples, which are important for
      memory consolidation. The mechanisms underlying ripple generation are not well
      understood. A prominent hypothesis holds that the ripples are generated by local
      recurrent networks of inhibitory neurons. Using computational models and
      experiments in brain slices from rodents, we show that the dynamics of
      interneuron networks clarify several previously unexplained characteristics of
      ripple oscillations, which advances our understanding of hippocampus-dependent
      memory consolidation.

PMID- 29453208
TI  - Parent-reported prevalence and persistence of 19 common child health conditions.
AB  - OBJECTIVE: To estimate prevalence and persistence of 19 common paediatric
      conditions from infancy to 14-15 years. DESIGN: Population-based prospective
      cohort study. SETTING: Australia. PARTICIPANTS: Parallel cohorts assessed
      biennially from 2004 to 2014 from ages 0-1 and 4-5 years to 10-11 and 14-15
      years, respectively, in the Longitudinal Study of Australian Children. MAIN
      OUTCOME MEASURES: 19 health conditions: 17 parent-reported, 2
      (overweight/obesity, obesity) directly assessed. Two general measures: health
      status, special health care needs. ANALYSIS: (1) prevalence estimated in 2-year
      age-bands and (2) persistence rates calculated at each subsequent time point for
      each condition among affected children. RESULTS: 10 090 children participated in
      Wave 1 and 6717 in all waves. From age 2, more than 60% of children were
      experiencing at least one health condition at any age. Distinct prevalence
      patterns by age-bands comprised eight conditions that steadily rose
      (overweight/obesity, obesity, injury, anxiety/depression, frequent headaches,
      abdominal pain, autism spectrum disorder, attention-deficit hyperactivity
      disorder). Six conditions fell with age (eczema, sleep problems, day-wetting,
      soiling, constipation, recurrent tonsillitis), three remained stable (asthma,
      diabetes, epilepsy) and two peaked in mid-childhood (dental decay, recurrent ear
      infections). Conditions were more likely to persist if present for 2 years;
      persistence was especially high for obesity beyond 6-7 (91.3%-95.1% persisting at
      14-15). CONCLUSIONS: Beyond infancy, most Australian children are experiencing at
      least one ongoing health condition at any given time. This study's age-specific
      estimates of prevalence and persistence should assist families and clinicians to
      plan care. Conditions showing little resolution (obesity, asthma, attention
      deficit hyperactivity disorder) require long-term planning and management.

PMID- 29453209
TI  - Recurrent epistaxis leading to diagnosis of primary sinonasal melanoma.
AB  - A 48-year-old man presented to urgent care with recurrent epistaxis over 6
      months. Initially, nosebleeds were controlled with packing or cautery.
      Ultimately, he was referred to ear, nose and throat department and underwent
      nasal endoscopy which revealed polypoid tissue. A biopsy of the polyp showed non
      specific inflammation with no evidence of malignancy. Follow-up maxillofacial CT
      revealed a large mass lesion in the right maxillary sinus, right nasal fossa,
      much of the ethmoids and right sphenoid, with destruction of adjacent bony
      structures. MRI revealed a mass in the right nasal cavity with extension into the
      ethmoid and anterior sphenoid sinus, anterior cranial fossa and medial orbits.
      Staging CT discovered metastatic disease in the adrenal glands and
      lymphadenopathy in the neck. The patient underwent endoscopic sinus surgery with
      debulking and tissue diagnosis of malignant melanoma. He completed radiation
      therapy to sinus and was subsequently enrolled in a clinical trial. Most recent
      imaging revealed complete metabolic response on positron emission tomography.

PMID- 29453210
TI  - Polymicrobial bacterial pericarditis and cardiac tamponade caused by pericardial
      penetration of an adjustable gastric band.
AB  - We describe a case of polymicrobial bacterial pericarditis with Klebsiella
      pneumoniae and Proteus mirabilis, caused by pericardial penetration of the tip of
      the catheter of a laparoscopic adjustable gastric band (LAGB). The patient
      developed a cardiac tamponade, and subsequently emergency pericardiocentesis was
      performed. Analysis of earlier CT scans showed that the tip of the catheter had
      migrated through the liver and through the diaphragm into the pericardium, and
      was in contact with the myocardium. After stabilisation he was operated to remove
      the LAGB. In this case report, we describe the chain of events that led to the
      polymicrobial pericarditis-a complication of LAGB placement that to our knowledge
      has thus far never been reported. We furthermore present a detailed literature
      review of all published cases of polymicrobial pericarditis and its causes.

PMID- 29453211
TI  - Fistulation between a colonic J-Pouch and the upper vagina in an irradiated
      pelvis: a rare complication following low anterior resection with colonic J-pouch
      anal anastomosis for rectal cancer.
AB  - Formation of a colonic J-pouch with anastomosis to the rectal stump is an
      accepted form of reconstruction after low anterior resection (LAR) for rectal
      carcinoma. It is thought this can help prevent the onset of LAR syndrome as well
      as improve the quality of life in the first two years following surgery.
      Rectovaginal fistulation is a recognised complication of this form of surgery
      usually occurring because of technical failure leading to inclusion of the
      vaginal wall into the stapled anastomosis. We present an as of yet unreported
      case of fistulation between the upper horizontal staple line of a colonic J-pouch
      the tip of the 'J'-which was formed extracorporeally with the posterior vaginal
      fornix. We postulate that pelvic irradiation was partly a causative factor
      alongside subsequent mechanical irritation. Ultimately, surgical intervention was
      required, following which the patient made a full recovery. Interposition of
      omentum may prevent this problem.

PMID- 29453212
TI  - Implant of a left atrial appendage occluder device (Watchman) and leadless pacing
      system (Micra) through the same venous access in a single sitting.
AB  - A left atrial appendage occluder device (Watchman) and leadless pacemaker (Micra)
      was implanted from a single right femoral vein access in a 73-year-old female
      patient with persistent atrial fibrillation and symptomatic tachy-brady syndrome
      and unable to take oral anticoagulants. Standard methods of implantation were
      followed for both procedures. The Watchman device was implanted first followed by
      dilatation of the same venous access site in order to implant Micra transcatheter
      pacing system. The patient tolerated the procedures well and there were no
      complications. At the end of 1 month, both the devices were found to be working
      well.

PMID- 29453213
TI  - The cat did it: erythema nodosum and additional atypical presentations of
      Bartonella henselae infection in immunocompetent hosts.
AB  - A healthy patient presented with painful skin lesions on the anterior surface of
      her legs. Erythema nodosum was diagnosed but all the usual causes were ruled out.
      The finding of bilateral enlarged axillary lymph nodes with necrosis and
      granulomas led to the diagnosis of Bartonella infection, an unusual cause of
      erythema nodosum. Imaging also revealed splenomegaly and small para-aortic lymph
      nodes. Up to one quarter of the patients with cat-scratch disease present
      atypically, a considerably higher prevalence than previously reported. A
      comprehensive review of the literature (PubMed, since inception, all languages)
      revealed a remarkable array of unusual presentations which are summarised and
      briefly discussed.

PMID- 29453214
TI  - Renal nutcracker syndrome in a young lady: unusual findings and endovascular
      management.
AB  - Nutcracker syndrome (NCS) is caused by compression of left renal vein (LRV),
      usually between the aorta and the superior mesenteric artery (SMA). This can lead
      to obstruction of flow into the inferior vena cava and secondary left renal
      venous hypertension. Despite potential serious consequences, diagnosing NCS is
      often challenging, circuitous and commonly delayed. We report an extremely unique
      case of NCS. A 34-year-old woman presented with left flank pain and discomfort.
      On investigation, it was found that high pressure in the LRV, due to compression
      by the SMA, had led to a large venous aneurysm that had caused pelviureteric
      junction obstruction and hydronephrosis. Management was with stenting of the LRV
      and coil embolisation of the venous aneurysm with excellent clinical outcome.

PMID- 29453215
TI  - Syncope and cardiogenic shock in an 80-year-old woman.

PMID- 29453216
TI  - Ankylosing Spondylitis Disease Activity Score (ASDAS): 2018 update of the
      nomenclature for disease activity states.

PMID- 29453217
TI  - Time spent in inactive disease before MTX withdrawal is relevant with regard to
      the flare risk in patients with JIA.
AB  - OBJECTIVES: To determine the reasons of methotrexate (MTX) discontinuation,
      frequency of adverse events (AE) and whether the time in inactive disease before
      MTX withdrawal disease is associated with the risk of disease flare. METHODS:
      Patients with juvenile idiopathic arthritis (JIA) beginning treatment with MTX
      were prospectively observed in the national JIA biologic register Biologika in
      der Kinderrheumatologie/Biologics in Paediatric Rheumatology and its follow-up
      register Juvenile arthritis Methotrexate/Biologics long-term Observation.
      Inactive disease was defined by a clinical Juvenile Arthritis Disease Activity
      Score <=1, flare after MTX discontinuation by reoccurrence of at least moderate
      disease activity or restart of treatment with a disease-modifying antirheumatic
      drug . RESULTS: MTX treatment was initiated in 1514 patients after a mean disease
      duration of 2.1 years (SD=2.8). 40% of the patients experienced oligoarticular
      onset of JIA. MTX was discontinued in 982 (64.9%) patients. Ineffectiveness
      (36.9%) and achieving inactive disease (32.1%) were the most common reasons.
      Among the latter (n=316), 184 (58.2%) patients experienced a flare on follow-up.
      The likelihood of a flare was a function of time in inactive disease prior to MTX
      discontinuation (HR 0.95; 95% CI 0.92 to 0.97). Patients with inactive disease
      for longer than 12 months had a significantly lower flare rate (58 of 119, 48.7%;
      HR 0.48; 95% CI 0.34 to 0.69). The most frequently reported AE was MTX
      intolerance, including nausea, aversion and vomiting, accounting for 441 events
      (13.0 events/100 exposure years) in 307 (20.3%) patients. CONCLUSIONS: Patients
      who spent at least 12 months in inactive disease before MTX discontinuation had a
      significantly lower flare rate.

PMID- 29453218
TI  - Metabolic and cardiovascular benefits of hydroxychloroquine in patients with
      rheumatoid arthritis: a systematic review and meta-analysis.

PMID- 29453219
TI  - European families reveal MHC class I and II associations with autoimmune-mediated
      congenital heart block.

PMID- 29453220
TI  - Identification of novel fusion transcripts in multiple myeloma.
AB  - AIMS: Multiple myeloma (MM) is a heterogeneous disease characterised by
      genetically complex abnormalities. The classical mutational spectrum includes
      recurrent chromosomal aberrations and gene-level mutations. Recurrent
      translocations involving the IGH gene such as t(11;14), t(4;14) and t(14;16) are
      well known. However, the presence of complex genetic abnormalities raises the
      possibility that fusions other than the recurrent IGH translocations exist. We
      therefore employed a targeted RNA-sequencing panel to identify novel putative
      fusions in a local cohort of MM. METHODS: Targeted RNA-sequencing was performed
      on 21 patient samples using the Illumina TruSight RNA Pan-Cancer Panel
      (comprising 1385 genes). Fusion calls were generated from the Illumina RNA
      Sequencing Alignment software (V.1.0.0). These samples had conventional
      cytogenetic and fluorescence in situ hybridisation data for the common recurrent
      chromosomal abnormalities (t(11;14), t(4;14), t(14;16) and 17p13 deletion). The
      MMRF CoMMpass dataset was analysed using the TopHat-fusion pipeline. RESULTS: A
      total of 10 novel fusions were identified by the TruSight RNA Pan-Cancer Panel.
      Two of these fusions, HGF/CACNA2D1 and SMC3/MXI1, were validated by reverse
      transcription PCR and Sanger sequencing as they involve genes that may have
      biological relevance in MM genesis. Four of these (MAP2K4/MAP2K4P1) are likely to
      be spurious secondary to misalignment of reads to a pseudogene. One record of the
      HGF/CACNA2D1 fusion was identified from the MMRF CoMMpass dataset. CONCLUSIONS:
      The identification of novel fusions offers insights into the biology of MM and
      might have clinical relevance. Further functional studies are required to
      determine the biological and clinical relevance of these novel fusions.

PMID- 29453222
TI  - Clear lens extraction for the management of primary angle closure glaucoma:
      surgical technique and refractive outcomes in the EAGLE cohort.
AB  - BACKGROUND: To describe the surgical technique and refractive outcomes following
      clear lens extraction (CLE) in the Effectiveness, in Angle-closure Glaucoma, of
      Lens Extraction trial. METHODS: Review of prospectively collected data from a
      multicentre, randomised controlled trial comparing CLE and laser peripheral
      iridotomy. Eligible participants were >=50 years old and newly diagnosed with (1)
      primary angle closure (PAC) with intraocular pressure above 30 mm Hg or (2) PAC
      glaucoma. We report the postoperative corrected distance visual acuity (CDVA) and
      refractive outcomes at 12 and 36 months postoperatively for those who underwent
      CLE. RESULTS: Of the 419 participants, 208 were randomised to CLE. Mean baseline
      CDVA was 77.9 (SD 12.4) letters and did not change significantly at 36 months
      when mean CDVA was 79.9 (SD 10.9) letters. Mean preoperative spherical
      equivalents were +1.7 (SD 2.3) and +0.08 (SD 0.95) diopters (D) at 36 months.
      Fifty-nine per cent and 85% eyes were within +/-0.5D and +/-1.0D of predicted
      refraction, respectively, at 36 months. CONCLUSIONS: Mean CDVA in patients
      undergoing CLE for angle-closure glaucoma appeared stable over the 3-year study
      period. Refractive error was significantly reduced with surgery but refractive
      predictability was suboptimal. TRIAL REGISTRATION NUMBER: 

PMID- 29453221
TI  - H3K9 demethylase KDM4E is an epigenetic regulator for bovine embryonic
      development and a defective factor for nuclear reprogramming.
AB  - Aberrant epigenetic reprogramming often results in developmental defects in
      somatic cell nuclear transfer (SCNT) embryos during embryonic genome activation
      (EGA). Bovine eight-cell SCNT embryos exhibit global hypermethylation of histone
      H3 lysine 9 tri- and di-methylation (H3K9me3/2), but the intrinsic reason for
      this remains elusive. Here, we provide evidence that two H3K9 demethylase genes,
      lysine-specific demethylase 4D (KDM4D) and 4E (KDM4E), are related to active
      H3K9me3/2 demethylation in in vitro fertilized (IVF) embryos and are deficiently
      expressed in cloned embryos at the time of EGA. Moreover, KDM4E plays a more
      crucial role in IVF and SCNT embryonic development, and overexpression of KDM4E
      can restore the global transcriptome, improve blastocyst formation and increase
      the cloning efficiency of SCNT embryos. Our results thereby indicate that KDM4E
      can function as a crucial epigenetic regulator of EGA and as an internal
      defective factor responsible for persistent H3K9me3/2 barriers to SCNT-mediated
      reprogramming. Furthermore, we show that interactions between RNA and KDM4E are
      essential for H3K9 demethylation during EGA. These observations advance the
      understanding of incomplete nuclear reprogramming and are of great importance for
      transgenic cattle procreation.

PMID- 29453223
TI  - Tissue engineering of retina and Bruch's membrane: a review of cells, materials
      and processes.
AB  - The biological, structural and functional configuration of Bruch's membrane (BM)
      is significantly relevant to age-related macular degeneration (AMD) and other
      chorioretinal diseases, and AMD is one of the leading causes of blindness in the
      elderly worldwide. The configuration may worsen along with the ageing of retinal
      pigment epithelium and BM that finally leads to AMD. Thus, the scaffold-based
      tissue-engineered retina provides an innovative alternative for retinal tissue
      repair. The cell and material requirements for retinal repair are discussed
      including cell sheet engineering, decellularised membrane and tissue-engineered
      membranes. Further, the challenges and potential in realising a whole tissue
      model construct for retinal regeneration are highlighted herein. This review
      article provides a framework for future development of tissue-engineered retina
      as a preclinical model and possible treatments for AMD.

PMID- 29453224
TI  - Simple limbal epithelial transplantation (SLET) in failed cultivated limbal
      epithelial transplantation (CLET) for unilateral chronic ocular burns.
AB  - AIMS: Cultivated limbal epithelial transplantation (CLET) fails in around 20%-30%
      of cases. This study aimed to report the clinical outcomes of autologous simple
      limbal epithelial transplantation (SLET) in eyes with recurrent unilateral limbal
      stem cell deficiency (LSCD) due to failure of CLET. METHODS: This was a
      prospective case series which included 30 eyes of 30 patients who underwent SLET
      between 2010 and 2016 after failure of one (n=24) or two (n=6) previous CLET
      procedures for chronic unilateral ocular burns. The primary outcome measure was
      success of SLET defined on the basis of relative improvement in five objective
      criteria: best corrected visual acuity (BCVA), and grades of symblepharon,
      corneal conjunctivalisation, vascularisation and opacification. RESULTS: At a
      mean follow-up of 2.3 years, 24 (80%) of the 30 eyes maintained a successful
      outcome. Kaplan-Meier analysis showed a 5-year survival probability of 77%+/-8%.
      At 1 year postoperatively statistically significant improvement was noted in BCVA
      (logarithm of the minimum angle of resolution of 3 to 1) and in the median grades
      of corneal conjunctivalisation (2 to 0), vascularisation (2 to 0) and
      opacification (2 to 1) (P<=0.0026). In 62.5% of successful cases, BCVA improved
      to 20/200 or better. The success rate of SLET in failed CLET was better than that
      of repeat CLET (53.5%, P=0.011). None of the donor eyes developed any
      complications. CONCLUSION: SLET is an effective alternative to CLET in eyes with
      recurrence of LSCD after previously failed CLET procedures. Since SLET is single
      staged and less expensive, it is probably preferable to repeating CLET.

PMID- 29453225
TI  - Prevalence of age-related macular degeneration associated genetic risk factors
      and 4-year progression data in the Irish population.
AB  - BACKGROUND/AIMS: Age-related macular degeneration (AMD) is estimated to affect
      196 million people >50 years old globally. Prevalence of AMD-associated genetic
      risk factors and rate of disease progression are unknown in Ireland. METHODS:
      Prevalence of AMD-associated genetic risk variants, complement factor H (CFH)
      rs1061170, age-related maculopathy susceptibility 2 (ARMS2) rs10490924, component
      3 (C3) rs2230199, complement factor B (CFB) rs641153 and superkiller viralicidic
      activity 2-like (SKIV2L) rs429608 and 4-year progression data in a population
      representative cohort (The Irish Longitudinal study on Ageing (TILDA)) were
      assessed. 4473 participants >=50 years were assessed. 4173 had no disease n=1843;
      44% male and n=2330; 56% female, mean age 60+/-9.0, 300 had AMD n=136; 45% male
      and n=164; 55% female, mean age 64+/-9.0. A 4-year follow-up was undertaken with
      66% of AMD cases attending. Progression and regression from early to late AMD
      were measured. Genetic association as indicators of disease and as predictors of
      progression were assessed by multinomial logistic regression. RESULTS: Older age
      and the presence of CFH and ARMS2 risk alleles are two main risk factors
      associated with the prevalence of AMD in the TILDA cohort. 23% progressed to a
      higher grade of AMD. Carriers of CFH risk allele showed a strong association for
      disease progression. Heterozygosity for ARMS2 risk allele predicted progression
      to late AMD. 75% of those who progressed from early to late disease had soft
      drusen and hyperpigmentation at baseline. CONCLUSIONS: The prevalence of risk
      associated genes and 4-year progression rates of AMD in this Ireland cohort are
      comparable with other Caucasian populations. CFH Y402H is associated with disease
      progression, with soft drusen and hyperpigmentation as high-risk features.

PMID- 29453227
TI  - LLM-Domain B-GATA Transcription Factors Play Multifaceted Roles in Controlling
      Greening in Arabidopsis.
AB  - Chlorophyll accumulation and chloroplast development are regulated at multiple
      levels during plant development. The paralogous LLM-domain B-GATA transcription
      factors GNC and GNL contribute to chlorophyll biosynthesis and chloroplast
      formation in light-grown Arabidopsis thaliana seedlings. Whereas there is already
      ample knowledge about the transcriptional regulation of GNC and GNL, the identity
      of their downstream targets is largely unclear. Here, we identified genes
      controlling greening directly downstream of the GATAs by integrating data from
      RNA-sequencing and microarray data sets. We found that genes encoding subunits of
      the Mg-chelatase complex and 3,8-divinyl protochlorophyllide a 8-vinyl reductase
      (DVR) likely function directly downstream of the GATAs and that DVR expression is
      limiting in the pale-green gnc gnl mutants. The GATAs also regulate the nucleus
      encoded SIGMA (SIG) factor genes, which control transcription in the chloroplast
      and suppress the greening defects of sig mutants. Furthermore, GNC and GNL act,
      at the gene expression level, in an additive manner with the GOLDEN2-LIKE1 (GLK1)
      and GLK2 transcription factor genes, which are also important for proper
      chlorophyll accumulation. We thus reveal that chlorophyll biosynthesis genes are
      directly controlled by LLM-domain B-GATAs and demonstrate that these
      transcription factors play an indirect role in the control of greening through
      regulating SIGMA factor genes.

PMID- 29453226
TI  - Modeling the human bone marrow niche in mice: From host bone marrow engraftment
      to bioengineering approaches.
AB  - Xenotransplantation of patient-derived samples in mouse models has been
      instrumental in depicting the role of hematopoietic stem and progenitor cells in
      the establishment as well as progression of hematological malignancies. The
      foundations for this field of research have been based on the development of
      immunodeficient mouse models, which provide normal and malignant human
      hematopoietic cells with a supportive microenvironment. Immunosuppressed and
      genetically modified mice expressing human growth factors were key milestones in
      patient-derived xenograft (PDX) models, highlighting the importance of developing
      humanized microenvironments. The latest major improvement has been the use of
      human bone marrow (BM) niche-forming cells to generate human-mouse chimeric BM
      tissues in PDXs, which can shed light on the interactions between human stroma
      and hematopoietic cells. Here, we summarize the methods used for human
      hematopoietic cell xenotransplantation and their milestones and review the latest
      approaches in generating humanized BM tissues in mice to study human normal and
      malignant hematopoiesis.

PMID- 29453230
TI  - Role of biomarkers in predicting the occurrence of thyroid neoplasms in radiation
      exposed children.
AB  - With increasing numbers of childhood cancer survivors who were treated with
      radiation, there is a need to evaluate potential biomarkers that could signal an
      increased risk of developing thyroid cancer. We aimed to examine the
      relationships between thyrotropin and thyroglobulin levels and the risk of
      developing thyroid nodules and cancer in a cohort of radiation-exposed children.
      764 subjects who were irradiated in the neck area as children were examined and
      followed for up to 25 years. All subjects underwent a clinical examination,
      measurements of thyrotropin, thyroglobulin levels and thyroid imaging. At
      baseline, 216 subjects had thyroid nodules and 548 did not. Of those with
      nodules, 176 underwent surgery with 55 confirmed thyroid cancers. During the
      follow-up, 147 subjects developed thyroid nodules including 22 with thyroid
      cancer. Thyroglobulin levels were higher in subjects with prevalent thyroid
      nodules (26.1 ng/mL vs 9.37 ng/mL; P < 0.001) and in those who had an initial
      normal examination but later developed thyroid nodules (11.2 ng/mL vs 8.87 ng/mL;
      P = 0.017). There was no relationship between baseline thyrotropin levels and the
      prevalent presence or absence of thyroid nodules, whether a prevalent neoplasm
      was benign or malignant, subsequent development of thyroid nodules during follow
      up or whether an incident nodule was benign or malignant. In conclusion, in
      radiation-exposed children, higher thyroglobulin levels indicated an increased
      risk of developing thyroid nodules but did not differentiate between benign and
      malignant neoplasms. There was no association between the baseline TSH level and
      the risk of developing thyroid nodules or cancer.

PMID- 29453228
TI  - Targeted Profiling of Arabidopsis thaliana Subproteomes Illuminates Co- and
      Posttranslationally N-Terminal Myristoylated Proteins.
AB  - N-terminal myristoylation, a major eukaryotic protein lipid modification, is
      difficult to detect in vivo and challenging to predict in silico. We developed a
      proteomics strategy involving subfractionation of cellular membranes, combined
      with separation of hydrophobic peptides by mass spectrometry-coupled liquid
      chromatography to identify the Arabidopsis thaliana myristoylated proteome. This
      approach identified a starting pool of 8837 proteins in all analyzed cellular
      fractions, comprising 32% of the Arabidopsis proteome. Of these, 906 proteins
      contain an N-terminal Gly at position 2, a prerequisite for myristoylation, and
      214 belong to the predicted myristoylome (comprising 51% of the predicted
      myristoylome of 421 proteins). We further show direct evidence of myristoylation
      in 72 proteins; 18 of these myristoylated proteins were not previously predicted.
      We found one myristoylation site downstream of a predicted initiation codon,
      indicating that posttranslational myristoylation occurs in plants. Over half of
      the identified proteins could be quantified and assigned to a subcellular
      compartment. Hierarchical clustering of protein accumulation combined with
      myristoylation and S-acylation data revealed that N-terminal double acylation
      influences redirection to the plasma membrane. In a few cases, MYR function
      extended beyond simple membrane association. This study identified hundreds of N
      acylated proteins for which lipid modifications could control protein
      localization and expand protein function.

PMID- 29453229
TI  - Crystal Structure of Plant Legumain Reveals a Unique Two-Chain State with pH
      Dependent Activity Regulation.
AB  - The vacuolar cysteine protease legumain can cleave and selectively rebuild
      peptide bonds, thereby vastly expanding the sequential repertoire of
      biomolecules. In this context, plant legumains have recently attracted particular
      interest. Furthermore, legumains have important roles in many physiological
      processes, including programmed cell death. Their efficient peptide bond ligase
      activity has gained tremendous interest in the design of cyclic peptides for drug
      design. However, the mechanistic understanding of these dual activities is
      incomplete and partly conflicting. Here, we present the crystal structure of a
      plant legumain, Arabidopsis thaliana isoform-gamma (AtLEGgamma). Employing a
      conserved legumain fold, the plant legumain AtLEGgamma revealed unique mechanisms
      of autoactivation, including a plant-specific two-chain activation state, which
      remains conformationally stable at neutral pH, which is a prerequisite for full
      ligase activity and survival in different cell compartments. The charge
      distribution around the alpha6-helix mediates the pH-dependent dimerization and
      serves as a gatekeeper for the active site, thus regulating its protease and
      ligase activity.

PMID- 29453231
TI  - Correction: CAR-T Cells Inflict Sequential Killing of Multiple Tumor Target
      Cells.

PMID- 29453233
TI  - Distinct Chemopreventive Effects of Aspirin in Diffuse and Intestinal-Type
      Gastric Cancer.
AB  - Introduction: Although aspirin/NSAIDs may have potential preventive effects on
      several cancers, it remains unclear on gastric cancer. The purpose of this study
      is to compare the risk of developing gastric cancer and the histologic changes of
      intestinal metaplasia and neutrophil infiltration, between aspirin/NSAID users
      and nonusers.Methods: Using an electronic endoscopy database in two hospitals
      from 1996 to 2017, we analyzed the data from patients with chronic gastritis who
      received aspirin or NSAIDs prior to upper gastrointestinal endoscopy. One-to-one
      propensity score matching was performed to compare the proportion of gastric
      cancer, intestinal metaplasia, and neutrophil infiltration between these drug
      users and nonusers.Results: We analyzed 2,082 aspirin users and 2,082 nonusers as
      well as 898 NSAID users and 898 nonusers. Six diffuse-type and 19 intestinal-type
      gastric cancer, 1,243 intestinal metaplasia, and 1,503 neutrophil infiltration
      patients were identified. The proportion of diffuse-type gastric cancer (0.05%)
      was 80% lower in aspirin users compared with the nonusers (0.24%), and there was
      no case of diffuse-type cancer in patients who took aspirin for more than 2
      years. In contrast, intestinal-type gastric cancer incidence was significantly
      higher in aspirin users (0.72%) compared with nonusers (0.14%). No significant
      differences in the incidence of gastric cancer were found between NSAID use and
      nonusers. NSAID use was significantly associated with decreased proportion of
      neutrophil infiltration compared with nonusers.Conclusion: Aspirin may have
      distinct effects between intestinal-type and diffuse-type gastric cancer
      development. Cancer Prev Res; 11(5); 279-86. (c)2018 AACR.

PMID- 29453234
TI  - Revisiting the Viability of the Developmental-Behavioral Health Care Workforce.

PMID- 29453232
TI  - A Randomized Multicenter Phase II Study of Docosahexaenoic Acid in Patients with
      a History of Breast Cancer, Premalignant Lesions, or Benign Breast Disease.
AB  - Obesity, a cause of subclinical inflammation, is a risk factor for the
      development of postmenopausal breast cancer and is associated with poorer cancer
      outcomes. Docosahexaenoic acid (DHA), an omega-3 fatty acid, possesses anti
      inflammatory properties. We hypothesized that treatment with DHA would reduce the
      expression of proinflammatory genes and aromatase, the rate-limiting enzyme for
      estrogen biosynthesis, in benign breast tissue of overweight/obese women. A
      randomized, placebo-controlled, double-blind phase II study of DHA given for 12
      weeks to overweight/obese women with a history of stage I-III breast cancer,
      DCIS/LCIS, Paget's disease, or proliferative benign breast disease was carried
      out. In this placebo controlled trial, the primary objective was to determine
      whether DHA (1,000 mg by mouth twice daily) reduced breast tissue levels of
      TNFalpha. Secondary objectives included evaluation of the effect of DHA on breast
      tissue levels of COX-2, IL1beta, aromatase, white adipose tissue inflammation,
      and gene expression by RNA-seq. Red blood cell fatty acid levels were measured to
      assess compliance. From July 2013 to November 2015, 64 participants were
      randomized and treated on trial (32 women per arm). Increased levels of omega-3
      fatty acids in red blood cells were detected following treatment with DHA (P <
      0.001) but not placebo. Treatment with DHA did not alter levels of TNFalpha (P =
      0.71), or other biomarkers including the transcriptome in breast samples.
      Treatment with DHA was overall well-tolerated. Although compliance was confirmed,
      we did not observe changes in the levels of prespecified biomarkers in the breast
      after treatment with DHA when compared with placebo. Cancer Prev Res; 11(4); 203
      14. (c)2018 AACRSee related editorial by Fabian and Kimler, p. 187.

PMID- 29453235
TI  - A Workforce Survey on Developmental-Behavioral Pediatrics.
AB  - BACKGROUND AND OBJECTIVES: Developmental-behavioral conditions are common,
      affecting ~15% of US children. The prevalence and complexity of these conditions
      are increasing despite long wait times and a limited pipeline of new providers.
      We surveyed a convenience sample of the developmental-behavioral pediatric (DBP)
      workforce to determine current practices, workforce trends, and future needs.
      METHODS: An electronic survey was e-mailed to 1568 members of the American
      Academy of Pediatrics Section on Developmental and Behavioral Pediatrics and
      Council on Children with Disabilities, the Society for Developmental and
      Behavioral Pediatrics, and the National Association of Pediatric Nurse
      Practitioners Developmental and Behavioral Mental Health Special Interest Group.
      RESULTS: The response rate was 48%. There were 411 fellowship-trained physicians,
      147 nonfellowship-trained physicians, and 125 nurse practitioners; 61% were
      women, 79% were white, and 5% were Hispanic. Physicians had a mean of 29 years
      since medical school graduation, and one-third planned to retire in 3 to 5 years.
      Nurse practitioners were earlier in their careers. Respondents reported long wait
      times for new appointments, clinician burnout, increased patient complexity and
      up to 50% additional time spent per visit in nonreimbursed clinical-care
      activities. Female subspecialists spent more time per visit in billable and
      nonbillable components of clinical care. CONCLUSIONS: The DBP workforce struggles
      to meet current service demands, with long waits for appointments, increased
      complexity, and high volumes of nonreimbursed care. Sex-based practice
      differences must be considered in future planning. The viability of the DBP
      subspecialty requires strategies to maintain and expand the workforce, improve
      clinical efficiency, and prevent burnout.

PMID- 29453236
TI  - DNMT3A DNA-Binding Residues Provide Specificity for CpG DNA Methylation.
AB  - DNMT3A-DNMT3L-DNA crystal structures provide a mechanism for DNMT3A
      methyltransferase activity.

PMID- 29453237
TI  - Asparagine Bioavailability Drives Breast Cancer Metastasis.
AB  - Asparagine depletion reduces breast cancer invasion and metastasis without
      affecting primary tumor growth.

PMID- 29453238
TI  - Natural Killer Cells Recruit Dendritic Cells to Promote Antitumor Immunity.
AB  - Natural killer (NK) cells recruit conventional type 1 dendritic cells (cDC1) to
      the tumor microenvironment.

PMID- 29453239
TI  - A Next-Generation Chimeric Antigen Receptor Induces JAK-STAT Signaling.
AB  - CAR-T cells designed to activate JAK-STAT signaling show enhanced persistence and
      antitumor activity.

PMID- 29453240
TI  - Arvinas, Pfizer Team Up on PROTACs.
AB  - Biotechnology startup Arvinas is developing proteolysis-targeting chimeras
      (PROTAC) that combat cancer by degrading disease-causing proteins. The company's
      first PROTACs will target prostate and breast cancers, and a recent deal with
      Pfizer will allow Arvinas to develop PROTACs for other cancer types.

PMID- 29453241
TI  - The PI3Kalpha Inhibitor Alpelisib Has Activity in PIK3CA-altered Tumors.
AB  - The PI3Kalpha inhibitor alpelisib achieved a 58.2% disease control rate in PIK3CA
      altered solid tumors.

PMID- 29453242
TI  - Single-subject SPM FDG-PET patterns predict risk of dementia progression in
      Parkinson disease.
AB  - OBJECTIVE: To evaluate the statistical parametric mapping (SPM) procedure for
      fluorodeoxyglucose (FDG)-PET imaging as a possible single-subject marker of
      progression to dementia in Parkinson disease (PD). METHODS: Fifty-four
      consecutive patients with PD without dementia (age at onset of 59.9 +/- 10.1
      years, disease duration of 5.3 +/- 3.4 years) entered the study. The patients
      underwent an extensive motor and cognitive assessment and a single-subject FDG
      PET SPM evaluation at baseline. A 4-year follow-up provided disease progression
      and dementia diagnosis. RESULTS: The FDG-PET SPM was evaluated by 2 expert raters
      allowing the identification of a "typical PD pattern" in 29 patients, whereas 25
      patients presented with "atypical patterns," namely, dementia with Lewy bodies
      (DLB)-like (n = 12), Alzheimer disease (AD)-like (n = 6), corticobasal syndrome
      (CBS)-like (n = 5), and frontotemporal dementia (FTD)-like (n = 2). At 4-year
      follow-up, 13 patients, all showing atypical brain metabolic patterns at
      baseline, progressed to dementia (PD dementia). The DLB- and AD-like SPM patterns
      were the best predictor for incident dementia (p < 0.005, sensitivity 85%,
      specificity 88%), independently from demographics or cognitive baseline
      classification. CONCLUSIONS: This study suggests that FDG-PET SPM at the single
      subject level might help in identifying patients with PD at risk of developing
      dementia.

PMID- 29453243
TI  - Peak perihemorrhagic edema correlates with functional outcome in intracerebral
      hemorrhage.
AB  - OBJECTIVE: To evaluate the association of perihemorrhagic edema (PHE) evolution
      and peak edema extent with day 90 functional outcome in patients with
      intracerebral hemorrhage (ICH) and identify pathophysiologic factors influencing
      edema evolution. METHODS: This retrospective cohort study included patients with
      spontaneous supratentorial ICH between January 2006 and January 2014. ICH and PHE
      volumes were studied using a validated semiautomatic volumetric algorithm.
      Multivariable logistic regression and propensity score matching (PSM) accounting
      for age, ICH volume, and location were used for assessing measures associated
      with functional outcome and PHE evolution. Clinical outcome on day 90 was
      assessed using the modified Rankin Scale (0-3 = favorable, 4-6 = poor). RESULTS:
      A total of 292 patients were included. Median age was 70 years (interquartile
      range [IQR] 62-78), median ICH volume on admission 17.7 mL (IQR 7.9-40.2).
      Besides established factors for functional outcome, i.e., ICH volume and
      location, age, intraventricular hemorrhage, and NIH Stroke Scale score on
      admission, multivariable logistic regression revealed peak PHE volume (odds ratio
      [OR] 0.984 [95% confidence interval (CI) 0.973-0.994]) as an independent
      predictor of day 90 outcome. Peak PHE volume was independently associated with
      initial PHE increase up to day 3 (OR 1.060 [95% CI 1.018-1.103]) and neutrophil
      to lymphocyte ratio on day 6 (OR 1.236 [95% CI 1.034-1.477; PSM cohort, n =
      124]). Initial PHE increase (PSM cohort, n = 224) was independently related to
      hematoma expansion (OR 3.647 [95% CI 1.533-8.679]) and fever burden on days 2-3
      (OR 1.456 [95% CI 1.103-1.920]). CONCLUSION: Our findings suggest that peak PHE
      volume represents an independent predictor of functional outcome after ICH.
      Inflammatory processes and hematoma expansion seem to be involved in PHE
      evolution and may represent important treatment targets.

PMID- 29453244
TI  - White matter change with apathy and impulsivity in frontotemporal lobar
      degeneration syndromes.
AB  - OBJECTIVE: To identify the white matter correlates of apathy and impulsivity in
      the major syndromes associated with frontotemporal lobar degeneration, using
      diffusion-weighted imaging and data from the PiPPIN (Pick's Disease and
      Progressive Supranuclear Palsy: Prevalence and Incidence) study. We included
      behavioral and language variants of frontotemporal dementia, corticobasal
      syndrome, and progressive supranuclear palsy. METHODS: Seventy patients and 30
      controls underwent diffusion tensor imaging at 3-tesla after detailed assessment
      of apathy and impulsivity. We used tract-based spatial statistics of fractional
      anisotropy and mean diffusivity, correlating with 8 orthogonal dimensions of
      apathy and impulsivity derived from a principal component analysis of
      neuropsychological, behavioral, and questionnaire measures. RESULTS: Three
      components were associated with significant white matter tract abnormalities.
      Carer-rated change in everyday skills, self-care, and motivation correlated with
      widespread changes in dorsal frontoparietal and corticospinal tracts, while carer
      observations of impulsive-apathetic and challenging behaviors revealed disruption
      in ventral frontotemporal tracts. Objective neuropsychological tests of cognitive
      control, reflection impulsivity, and reward responsiveness were associated with
      focal changes in the right frontal lobe and presupplementary motor area. These
      changes were observed across clinical diagnostic groups, and were not restricted
      to the disorders for which diagnostic criteria include apathy and impulsivity.
      CONCLUSION: The current study provides evidence of distinct structural network
      changes in white matter associated with different neurobehavioral components of
      apathy and impulsivity across the diverse spectrum of syndromes and pathologies
      associated with frontotemporal lobar degeneration.

PMID- 29453245
TI  - Early vs late age at onset frontotemporal dementia and frontotemporal lobar
      degeneration.
AB  - OBJECTIVE: To examine clinicopathologic correlations in early vs late age at
      onset frontotemporal dementia (FTD) and frontotemporal lobar degeneration (FTLD).
      METHODS: All patients were clinically evaluated and prospectively diagnosed at
      the UCSF Memory and Aging Center. Two consecutive series were included: (1)
      patients with a clinically diagnosed FTD syndrome who underwent autopsy (cohort
      1) and (2) patients with a primary pathologic diagnosis of FTLD, regardless of
      the clinical syndrome (cohort 2). These series were divided by age at symptom
      onset (cutoff 65 years). RESULTS: In cohort 1, 48 (25.3%) were 65 years or older
      at symptom onset. Pathologic causes of behavioral variant FTD (bvFTD) were
      similar in the early age at onset (EO) and late age at onset (LO) bvFTD groups.
      In corticobasal syndrome (CBS), however, the most common pathologic substrate
      differed according to age at onset: progressive supranuclear palsy (42.9%) in LO
      CBS and Alzheimer disease (AD; 40.7%) in EO-CBS. In cohort 2, 57 (28.4%) were
      classified as LO-FTLD. Regarding FTLD major molecular classes, FTLD with
      transactive response DNA-binding protein of 43 kDa was most common in EO-FTLD
      (44.4%), whereas FTLD-tau (58.3%) was most common in LO-FTLD. Antemortem
      diagnosis of a non-FTD syndrome, usually AD-type dementia, was more frequent in
      LO-FTLD than EO-FTLD (19.3% vs 7.7%, p = 0.017). LO-FTLD was also associated with
      more prevalent comorbid pathologic changes. Of these, moderate to severe AD
      neuropathologic change and argyrophilic grain disease were overrepresented among
      patients who received an antemortem diagnosis of AD-type dementia. CONCLUSION:
      Patients with FTD and FTLD often develop symptoms after age 65, and age at onset
      represents an important consideration when making antemortem neuropathologic
      predictions.

PMID- 29453246
TI  - Yield of the RYR2 Genetic Test in Suspected Catecholaminergic Polymorphic
      Ventricular Tachycardia and Implications for Test Interpretation.
AB  - BACKGROUND: Pathogenic RYR2 variants account for ~60% of clinically definite
      cases of catecholaminergic polymorphic ventricular tachycardia. However, the rate
      of rare benign RYR2 variants identified in the general population remains a
      challenge for genetic test interpretation. Therefore, we examined the results of
      the RYR2 genetic test among patients referred for commercial genetic testing and
      examined factors impacting variant interpretability. METHODS: Frequency and
      location comparisons were made for RYR2 variants identified among 1355 total
      patients of varying clinical certainty and 60 706 Exome Aggregation Consortium
      controls. The impact of the clinical phenotype on the yield of RYR2 variants was
      examined. Six in silico tools were assessed using patient- and control-derived
      variants. RESULTS: A total of 18.2% (218/1200) of patients referred for
      commercial testing hosted rare RYR2 variants, statistically less than the 59%
      (46/78) yield among clinically definite cases, resulting in a much higher
      potential genetic false discovery rate among referrals considering the 3.2%
      background rate of rare, benign RYR2 variants. Exclusion of clearly putative
      pathogenic variants further complicates the interpretation of the next novel RYR2
      variant. Exonic/topologic analyses revealed overrepresentation of patient
      variants in exons covering only one third of the protein. In silico tools largely
      failed to show evidence toward enhancement of variant interpretation.
      CONCLUSIONS: Current expert recommendations have resulted in increased use of
      RYR2 genetic testing in patients with questionable clinical phenotypes. Using the
      largest to date catecholaminergic polymorphic ventricular tachycardia patient
      versus control comparison, this study highlights important variables in the
      interpretation of variants to overcome the 3.2% background rate that confounds
      RYR2 variant interpretation.

PMID- 29453247
TI  - BCL2L11 Is Associated With Kawasaki Disease in Intravenous Immunoglobulin
      Responder Patients.

PMID- 29453248
TI  - Is Careful Assessment of Rare Variants in the RYR2 Gene Piercing the Guidelines'
      Strong Armor?

PMID- 29453249
TI  - Hhex induces promyelocyte self-renewal and cooperates with growth factor
      independence to cause myeloid leukemia in mice.
AB  - The hematopoietically expressed homeobox (Hhex) transcription factor is
      overexpressed in human myeloid leukemias. Conditional knockout models of murine
      acute myeloid leukemia indicate that Hhex maintains leukemia stem cell self
      renewal by enabling Polycomb-mediated epigenetic repression of the Cdkn2a tumor
      suppressor locus, encoding p16Ink4a and p19Arf However, whether Hhex
      overexpression also affects hematopoietic differentiation is unknown. To study
      this, we retrovirally overexpressed Hhex in hematopoietic progenitors. This
      enabled serial replating of myeloid progenitors, leading to the rapid
      establishment of interleukin-3 (IL-3)-dependent promyelocytic cell lines. Use of
      a Hhex-ERT2 fusion protein demonstrated that continuous nuclear Hhex is required
      for transformation, and structure function analysis demonstrated a requirement of
      the DNA-binding and N-terminal-repressive domains of Hhex for promyelocytic
      transformation. This included the N-terminal promyelocytic leukemia protein (Pml)
      interaction domain, although deletion of Pml failed to prevent Hhex-induced
      promyelocyte transformation, implying other critical partners. Furthermore,
      deletion of p16Ink4a or p19Arf did not promote promyelocyte transformation,
      indicating that repression of distinct Hhex target genes is required for this
      process. Indeed, transcriptome analysis showed that Hhex overexpression resulted
      in repression of several myeloid developmental genes. To test the potential for
      Hhex overexpression to contribute to leukemic transformation, Hhex-transformed
      promyelocyte lines were rendered growth factor-independent using a constitutively
      active IL-3 receptor common beta subunit (betacV449E). The resultant cell lines
      resulted in a rapid promyelocytic leukemia in vivo. Thus, Hhex overexpression can
      contribute to myeloid leukemia via multiple mechanisms including differentiation
      blockade and enabling epigenetic repression of the Cdkn2a locus.

PMID- 29453250
TI  - Retinal-chitosan Conjugates Effectively Deliver Active Chromophores to Retinal
      Photoreceptor Cells in Blind Mice and Dogs.
AB  - The retinoid (visual) cycle consists of a series of biochemical reactions needed
      to regenerate the visual chromophore 11-cis-retinal and sustain vision. Genetic
      or environmental factors affecting chromophore production can lead to blindness.
      Using animal models that mimic human retinal diseases, we previously demonstrated
      that mechanism-based pharmacological interventions can maintain vision in
      otherwise incurable genetic diseases of the retina. Here, we report that after 9
      cis-retinal administration to lecithin:retinol acyltransferase-deficient (Lrat-/-
      ) mice, the drug was rapidly absorbed and then cleared within 1 to 2 hours.
      However, when conjugated to form chitosan-9-cis-retinal, this prodrug was slowly
      absorbed from the gastrointestinal tract, resulting in sustainable plasma levels
      of 9-cis-retinol and recovery of visual function without causing elevated levels,
      as occurs with unconjugated drug treatment. Administration of chitosan-9-cis
      retinal conjugate intravitreally in retinal pigment epithelium-specific 65
      retinoid isomerase (RPE65)-deficient dogs improved photoreceptor function as
      assessed by electroretinography. Functional rescue was dose dependent and
      maintained for several weeks. Dosing via the gastrointestinal tract in canines
      was found ineffective, most likely due to peculiarities of vitamin A blood
      transport in canines. Use of the chitosan conjugate in combination with 11-cis-6
      ring-retinal, a locked ring analog of 11-cis-retinal that selectively blocks rod
      opsin consumption of chromophore while largely sparing cone opsins, was found to
      prolong cone vision in Lrat-/- mice. Development of such combination low-dose
      regimens to selectively prolong useful cone vision could not only expand retinal
      disease treatments to include Leber congenital amaurosis but also the age-related
      decline in human dark adaptation from progressive retinoid cycle deficiency.

PMID- 29453251
TI  - Novel Adipokine, FAM19A5, Inhibits Neointima Formation After Injury Through
      Sphingosine-1-Phosphate Receptor 2.
AB  - BACKGROUND: Obesity plays crucial roles in the development of cardiovascular
      diseases. However, the mechanisms that link obesity and cardiovascular diseases
      remain elusive. Compelling evidence indicates that adipokines play an important
      role in obesity-related cardiovascular diseases. Here, we found a new adipokine
      named family with sequence similarity 19, member A5 (FAM19A5), a protein with
      unknown function that was predicted to be distantly related to the CC-chemokine
      family. We aimed to test whether adipose-derived FAM19A5 regulates vascular
      pathology on injury. METHODS: DNA cloning, protein expression, purification, and
      N-terminal sequencing were applied to characterize FAM19A5. Adenovirus infection
      and siRNA transfection were performed to regulate FAM19A5 expression. Balloon and
      wire injury were performed in vivo on the rat carotid arteries and mouse femoral
      arteries, respectively. Bioinformatics analysis, radioactive ligand-receptor
      binding assays, receptor internalization, and calcium mobilization assays were
      used to identify the functional receptor for FAM19A5. RESULTS: We first
      characterized FAM19A5 as a secreted protein, and the first 43 N-terminal amino
      acids were the signal peptides. Both FAM19A5 mRNA and protein were abundantly
      expressed in the adipose tissue but were downregulated in obese mice.
      Overexpression of FAM19A5 markedly inhibited vascular smooth muscle cell
      proliferation and migration and neointima formation in the carotid arteries of
      balloon-injured rats. Accordingly, FAM19A5 silencing in adipocytes significantly
      promoted vascular smooth muscle cell activation. Adipose-specific FAM19A5
      transgenic mice showed greater attenuation of neointima formation compared with
      wild-type littermates fed with or without Western-style diet. We further revealed
      that sphingosine-1-phosphate receptor 2 was the functional receptor for FAM19A5,
      with a dissociation constant (Kd) of 0.634 nmol/L. Inhibition of sphingosine-1
      phosphate receptor 2 or its downstream G12/13-RhoA signaling circumvented the
      suppressive effects of FAM19A5 on vascular smooth muscle cell proliferation and
      migration. CONCLUSIONS: We revealed that a novel adipokine, FAM19A5, was capable
      of inhibiting postinjury neointima formation via sphingosine-1-phosphate receptor
      2-G12/13-RhoA signaling. Downregulation of FAM19A5 during obesity may trigger
      cardiometabolic diseases.

PMID- 29453252
TI  - Ecology and Biotechnological Potential of Bacteria Belonging to the Genus
      Pseudovibrio.
AB  - Members of the genus Pseudovibrio have been isolated worldwide from a great
      variety of marine sources as both free-living and host-associated bacteria. So
      far, the available data depict a group of alphaproteobacteria characterized by a
      versatile metabolism, which allows them to use a variety of substrates to meet
      their carbon, nitrogen, sulfur, and phosphorous requirements. Additionally,
      Pseudovibrio-related bacteria have been shown to proliferate under extreme
      oligotrophic conditions, tolerate high heavy-metal concentrations, and metabolize
      potentially toxic compounds. Considering this versatility, it is not surprising
      that they have been detected from temperate to tropical regions and are often the
      most abundant isolates obtained from marine invertebrates. Such an association is
      particularly recurrent with marine sponges and corals, animals that play a key
      role in benthic marine systems. The data so far available indicate that these
      bacteria are mainly beneficial to the host, and besides being involved in major
      nutrient cycles, they could provide the host with both vitamins/cofactors and
      protection from potential pathogens via the synthesis of antimicrobial secondary
      metabolites. In fact, the biosynthetic abilities of Pseudovibrio spp. have been
      emerging in recent years, and both genomic and analytic studies have underlined
      how these organisms promise novel natural products of biotechnological value.

PMID- 29453253
TI  - Assembly of Synthetic Functional Cellulosomal Structures onto the Cell Surface of
      Lactobacillus plantarum, a Potent Member of the Gut Microbiome.
AB  - Heterologous display of enzymes on microbial cell surfaces is an extremely
      desirable approach, since it enables the engineered microbe to interact directly
      with the plant wall extracellular polysaccharide matrix. In recent years,
      attempts have been made to endow noncellulolytic microbes with genetically
      engineered cellulolytic capabilities for improved hydrolysis of lignocellulosic
      biomass and for advanced probiotics. Thus far, however, owing to the hurdles
      encountered in secreting and assembling large, intricate complexes on the
      bacterial cell wall, only free cellulases or relatively simple cellulosome
      assemblies have been introduced into live bacteria. Here, we employed the
      "adaptor scaffoldin" strategy to compensate for the low levels of protein
      displayed on the bacterial cell surface. That strategy mimics natural elaborated
      cellulosome architectures, thus exploiting the exponential features of their Lego
      like combinatorics. Using this approach, we produced several bacterial consortia
      of Lactobacillus plantarum, a potent gut microbe which provides a very robust
      genetic framework for lignocellulosic degradation. We successfully engineered
      surface display of large, fully active self-assembling cellulosomal complexes
      containing an unprecedented number of catalytic subunits all produced in vivo by
      the cell consortia. Our results demonstrate that the enzyme stability and
      performance of the cellulosomal machinery, which are superior to those seen with
      the equivalent secreted free enzyme system, and the high cellulase-to-xylanase
      ratios proved beneficial for efficient degradation of wheat straw.IMPORTANCE The
      multiple benefits of lactic acid bacteria are well established in health and
      industry. Here we present an approach designed to extensively increase the cell
      surface display of proteins via successive assembly of interactive components.
      Our findings present a stepping stone toward proficient engineering of
      Lactobacillus plantarum, a widespread, environmentally important bacterium and
      potent microbiome member, for improved degradation of lignocellulosic biomass and
      advanced probiotics.

PMID- 29453254
TI  - Versatile Cas9-Driven Subpopulation Selection Toolbox for Lactococcus lactis.
AB  - CRISPR-Cas9 technology has been exploited for the removal or replacement of
      genetic elements in a wide range of prokaryotes and eukaryotes. Here, we describe
      the extension of the Cas9 application toolbox to the industrially important dairy
      species Lactococcus lactis The Cas9 expression vector pLABTarget, encoding the
      Streptocccus pyogenes Cas9 under the control of a constitutive promoter, was
      constructed, allowing plug and play introduction of short guide RNA (sgRNA)
      sequences to target specific genetic loci. Introduction of a pepN-targeting
      derivative of pLABTarget into L. lactis strain MG1363 led to a strong reduction
      in the number of transformants obtained, which did not occur in a pepN deletion
      derivative of the same strain, demonstrating the specificity and lethality of the
      Cas9-mediated double-strand breaks in the lactococcal chromosome. Moreover, the
      same pLABTarget derivative allowed the selection of a pepN deletion subpopulation
      from its corresponding single-crossover plasmid integrant precursor, accelerating
      the construction and selection of gene-specific deletion derivatives in L. lactis
      Finally, pLABTarget, which contained sgRNAs designed to target mobile genetic
      elements, allowed the effective curing of plasmids, prophages, and integrative
      conjugative elements (ICEs). These results establish that pLABTarget enables the
      effective exploitation of Cas9 targeting in L. lactis, while the broad-host-range
      vector used suggests that this toolbox could readily be expanded to other Gram
      positive bacteria.IMPORTANCE Mobile genetic elements in Lactococcus lactis and
      other lactic acid bacteria (LAB) play an important role in dairy fermentation,
      having both positive and detrimental effects during the production of fermented
      dairy products. The pLABTarget vector offers an efficient cloning platform for
      Cas9 application in lactic acid bacteria. Targeting Cas9 toward mobile genetic
      elements enabled their effective curing, which is of particular interest in the
      context of potentially problematic prophages present in a strain. Moreover, Cas9
      targeting of other mobile genetic elements enables the deciphering of their
      contribution to dairy fermentation processes and further establishment of their
      importance for product characteristics.

PMID- 29453255
TI  - Endophyte-Mediated Modulation of Defense-Related Genes and Systemic Resistance in
      Withania somnifera (L.) Dunal under Alternaria alternata Stress.
AB  - Endophytes have been explored and found to perform an important role in plant
      health. However, their effects on the host physiological function and disease
      management remain elusive. The present study aimed to assess the potential
      effects of endophytes, singly as well as in combination, in Withania somnifera
      (L.) Dunal, on various physiological parameters and systemic defense mechanisms
      against Alternaria alternata Seeds primed with the endophytic bacteria Bacillus
      amyloliquefaciens and Pseudomonas fluorescens individually and in combination
      demonstrated an enhanced vigor index and germination rate. Interestingly, plants
      treated with the two-microbe combination showed the lowest plant mortality rate
      (28%) under A. alternata stress. Physiological profiling of treated plants showed
      improved photosynthesis, respiration, transpiration, and stomatal conductance
      under pathogenic stress. Additionally, these endophytes not only augmented
      defense enzymes and antioxidant activity in treated plants but also enhanced the
      expression of salicylic acid- and jasmonic acid-responsive genes in the stressed
      plants. Reductions in reactive oxygen species (ROS) and reactive nitrogen species
      (RNS) along with enhanced callose deposition in host plant leaves corroborated
      well with the above findings. Altogether, the study provides novel insights into
      the underlying mechanisms behind the tripartite interaction of endophyte-A.
      alternata-W. somnifera and underscores their ability to boost plant health under
      pathogen stress.IMPORTANCEW. somnifera is well known for producing several
      medicinally important secondary metabolites. These secondary metabolites are
      required by various pharmaceutical sectors to produce life-saving drugs. However,
      the cultivation of W. somnifera faces severe challenge from leaf spot disease
      caused by A. alternata To keep pace with the rising demand for this plant and
      considering its capacity for cultivation under field conditions, the present
      study was undertaken to develop approaches to enhance production of W. somnifera
      through intervention using endophytes. Application of bacterial endophytes not
      only suppresses the pathogenicity of A. alternata but also mitigates excessive
      ROS/RNS generation via enhanced physiological processes and antioxidant
      machinery. Expression profiling of plant defense-related genes further validates
      the efficacy of bacterial endophytes against leaf spot disease.

PMID- 29453256
TI  - Structural Characterization and Directed Evolution of a Novel Acetyl Xylan
      Esterase Reveals Thermostability Determinants of the Carbohydrate Esterase 7
      Family.
AB  - A hot desert hypolith metagenomic DNA sequence data set was screened in silico
      for genes annotated as acetyl xylan esterases (AcXEs). One of the genes
      identified encoded an ~36-kDa protein (Axe1NaM1). The synthesized gene was cloned
      and expressed, and the resulting protein was purified. NaM1 was optimally active
      at pH 8.5 and 30 degrees C and functionally stable at salt concentrations of up
      to 5 M. The specific activity and catalytic efficiency were 488.9 U mg-1 and 3.26
      * 106 M-1 s-1, respectively. The crystal structure of wild-type NaM1 was solved
      at a resolution of 2.03 A, and a comparison with the structures and models of
      more thermostable carbohydrate esterase 7 (CE7) family enzymes and variants of
      NaM1 from a directed evolution experiment suggests that reduced side-chain volume
      of protein core residues is relevant to the thermal stability of NaM1.
      Surprisingly, a single point mutation (N96S) not only resulted in a simultaneous
      improvement in thermal stability and catalytic efficiency but also increased the
      acyl moiety substrate range of NaM1.IMPORTANCE AcXEs belong to nine carbohydrate
      esterase families (CE1 to CE7, CE12, and CE16), of which CE7 enzymes possess a
      unique and narrow specificity for acetylated substrates. All structurally
      characterized members of this family are moderately to highly thermostable. The
      crystal structure of a novel, mesophilic CE7 AcXE (Axe1NaM1), from a soil
      metagenome, provides a basis for comparisons with thermostable CE7 enzymes. Using
      error-prone PCR and site-directed mutagenesis, we enhanced both the stability and
      activity of the mesophilic AcXE. With comparative structural analyses, we have
      also identified possible thermal stability determinants. These are valuable for
      understanding the thermal stability of enzymes within this family and as a guide
      for future protein engineering of CE7 and other alpha/beta hydrolase enzymes.

PMID- 29453257
TI  - Facile Arsenazo III-Based Assay for Monitoring Rare Earth Element Depletion from
      Cultivation Media for Methanotrophic and Methylotrophic Bacteria.
AB  - Recently, methanotrophic and methylotrophic bacteria were found to utilize rare
      earth elements (REEs). To monitor the REE content in culture media of these
      bacteria, we have developed a rapid screening method using the Arsenazo III (AS
      III) dye for spectrophotometric REE detection in the low MUM (0.1 to 10 MUM)
      range. We designed this assay to follow LaIII and EuIII depletion from the
      culture medium by the acidophilic verrucomicrobial methanotroph Methylacidiphilum
      fumariolicum strain SolV. The assay can also be modified to screen the uptake of
      other REEs, such as PrIII, or to monitor the depletion of LaIII from growth media
      in neutrophilic methylotrophs such as Methylobacterium extorquens strain AM1. The
      AS III assay presents a convenient and fast detection method for REE levels in
      culture media and is a sensitive alternative to inductively coupled plasma mass
      spectrometry (ICP-MS) or atomic absorption spectroscopy (AAS).IMPORTANCE REE
      dependent bacterial metabolism is a quickly emerging field, and while the
      importance of REEs for both methanotrophic and methylotrophic bacteria is now
      firmly established, many important questions, such as how these insoluble
      elements are taken up into cells, are still unanswered. Here, an Arsenazo III dye
      based assay has been developed for fast, specific, and sensitive determination of
      REE content in different culture media. This assay presents a useful tool for
      optimizing cultivation protocols, as well as for routine REE monitoring during
      bacterial growth without the need for specialized analytical instrumentation.
      Furthermore, this assay has the potential to promote the discovery of other REE
      dependent microorganisms and can help to elucidate the mechanisms for acquisition
      of REEs by methanotrophic and methylotrophic bacteria.

PMID- 29453258
TI  - Anthropogenic N Deposition Alters the Composition of Expressed Class II Fungal
      Peroxidases.
AB  - Here, we present evidence that ca. 20 years of experimental N deposition altered
      the composition of lignin-decaying class II peroxidases expressed by forest floor
      fungi, a response which has occurred concurrently with reductions in plant litter
      decomposition and a rapid accumulation of soil organic matter. This finding
      suggests that anthropogenic N deposition has induced changes in the biological
      mediation of lignin decay, the rate limiting step in plant litter decomposition.
      Thus, an altered composition of transcripts for a critical gene that is
      associated with terrestrial C cycling may explain the increased soil C storage
      under long-term increases in anthropogenic N deposition.IMPORTANCE Fungal class
      II peroxidases are enzymes that mediate the rate-limiting step in the
      decomposition of plant material, which involves the oxidation of lignin and other
      polyphenols. In field experiments, anthropogenic N deposition has increased soil
      C storage in forests, a result which could potentially arise from anthropogenic N
      induced changes in the composition of class II peroxidases expressed by the
      fungal community. In this study, we have gained unique insight into how
      anthropogenic N deposition, a widespread agent of global change, affects the
      expression of a functional gene encoding an enzyme that plays a critical role in
      a biologically mediated ecosystem process.

PMID- 29453259
TI  - Common Hydraulic Fracturing Fluid Additives Alter the Structure and Function of
      Anaerobic Microbial Communities.
AB  - The development of unconventional oil and gas (UOG) resources results in the
      production of large volumes of wastewater containing a complex mixture of
      hydraulic fracturing chemical additives and components from the formation. The
      release of these wastewaters into the environment poses potential risks that are
      poorly understood. Microbial communities in stream sediments form the base of the
      food chain and may serve as sentinels for changes in stream health. Iron-reducing
      organisms have been shown to play a role in the biodegradation of a wide range of
      organic compounds, and so to evaluate their response to UOG wastewater, we
      enriched anaerobic microbial communities from sediments collected upstream
      (background) and downstream (impacted) of an UOG wastewater injection disposal
      facility in the presence of hydraulic fracturing fluid (HFF) additives: guar gum,
      ethylene glycol, and two biocides, 2,2-dibromo-3-nitrilopropionamide (DBNPA) and
      bronopol (C3H6BrNO4). Iron reduction was significantly inhibited early in the
      incubations with the addition of biocides, whereas amendment with guar gum and
      ethylene glycol stimulated iron reduction relative to levels in the unamended
      controls. Changes in the microbial community structure were observed across all
      treatments, indicating the potential for even small amounts of UOG wastewater
      components to influence natural microbial processes. The microbial community
      structure differed between enrichments with background and impacted sediments,
      suggesting that impacted sediments may have been preconditioned by exposure to
      wastewater. These experiments demonstrated the potential for biocides to
      significantly decrease iron reduction rates immediately following a spill and
      demonstrated how microbial communities previously exposed to UOG wastewater may
      be more resilient to additional spills.IMPORTANCE Organic components of UOG
      wastewater can alter microbial communities and biogeochemical processes, which
      could alter the rates of essential natural attenuation processes. These findings
      provide new insights into microbial responses following a release of UOG
      wastewaters and are critical for identifying strategies for the remediation and
      natural attenuation of impacted environments.

PMID- 29453260
TI  - A new cell extraction method reveals hemolymph microbiome of three aquatic
      invertebrates.
AB  - Symbiotic microorganisms have been found in the hemolymph (blood) of many aquatic
      invertebrates, such as crabs, shrimps and oysters. Hemolymph is a critical site
      in host immune response. Currently, studies on hemolymph microorganisms are
      mostly performed with culture-dependent strategies using selective media (e.g.,
      TCBS, 2216E, and LB) for enumerating and isolating microbial cells. However,
      doubts remain about the "true" representation of the microbial abundance and
      diversity of symbiotic microorganisms in hemolymph, particularly for uncultivable
      microorganisms which are believed to be more abundant than the cultured. To
      explore this, we developed a culture-independent cell extraction method for
      separating microbial cells from the hemolymph of three aquatic invertebrates
      (Scylla paramamosain, Litopenaeus vannamei, and Crassostrea angulata) involving
      filtration through a 5-MUm mesh filter membrane (the Filtration Method). A
      combination of the Filtration Method with fluorescence microscopy and high
      throughput sequencing technique provides insight into the abundances and
      diversity of the total microbiota in the hemolymph of these three invertebrates.
      More than 2.6 * 104 cells/mL of microbial cells dominated by Escherichia-Shigella
      and Halomonas, Photobacterium and Escherichia-Shigella, and Pseudoalteromonas and
      Arcobacter, were detected in the hemolymph of Scylla paramamosain, Litopenaeus
      vannamei, and Crassostrea angulata, respectively. A parallel study for
      investigating the hemolymph microbiome by comparing the Filtration Method and a
      culture-dependent method (the Plate Count Method), showed significantly higher
      microbial abundances (between 26 and 369-folds difference; P<0.05) and less
      biased community structures of the Filtration Method than those of the Plate
      Count Method. Furthermore, hemolymph of the three invertebrates harbored many
      potential pathogens, including Photobacterium, Arcobacter, and Vibrio Finally,
      the Filtration Method provides a solution that improves understanding of the
      metabolic functions of uncultivable hemolymph microorganisms (e.g., metagenomics)
      devoid of host hemocytes contamination.Importance Microorganisms are found in
      invertebrates' hemolymph, a critical site in host immune response. Currently,
      studies on hemolymph microorganisms are mostly performed with culture-dependent
      strategies. However, doubts remain about the "true" representation of hemolymph
      microbiome. This study developed a culture-independent cell extraction method
      that could separate microbial cells from the hemolymph of three aquatic
      invertebrates (S. paramamosain, L. vannamei, and C. angulata) based on filtration
      through a 5-MUm mesh filter membrane (the Filtration Method). A combination of
      the Filtration Method with fluorescence microscopy and high-throughput sequencing
      technique provides insight into the abundances and diversity of the total
      microbiota in the hemolymph of these three invertebrates. Our results demonstrate
      that the hemolymph of aquatic invertebrates harbors a much higher microbial
      abundance and distinct microbial community composition than previously estimated.
      Furthermore, this work provides a less biased solution for studying the metabolic
      functions of uncultivable hemolymph microbiota devoid of host hemocytes
      contamination.

PMID- 29453261
TI  - Molecular and Functional Study of a Branching Sucrase-Like Glucansucrase Reveals
      an Evolutionary Intermediate between Two Subfamilies of the GH70 Enzymes.
AB  - Glucansucrases (GSs) in glycoside hydrolase family 70 (GH70) catalyze the
      synthesis of alpha-glucans from sucrose, a reaction that is widely seen in lactic
      acid bacteria (LAB). These enzymes have been implicated in many aspects of
      microbial life. Products of GSs have great commercial value as food supplements
      and medical materials; therefore, these enzymes have attracted much attention
      from both science and industry. Certain issues concerning the origin and
      evolution of GSs are still to be addressed, although an increasing number of GH70
      enzymes have been characterized. This study describes a GS enzyme with the
      appearance of a branching sucrase (BrS). Structural analysis indicated that this
      GS enzyme produced a type of glucan composed of an alpha-(1->6) glucosidic
      backbone and alpha-(1->4) branches, as well as a considerable amount of alpha-(1
      >3) branches, distinguishing it from the GSs identified so far. Moreover,
      sequence-based analysis of the catalytic core of this enzyme suggested that it
      might be an evolutionary intermediate between the BrS and GS subgroups. These
      results provide an evolutionary link between these subgroups of GH70 enzymes and
      shed new light on the origination of GSs.IMPORTANCE GH70 GSs catalyze the
      synthesis of alpha-glucans from sucrose, a reaction that is widely seen in LAB.
      Products of these enzymes have great commercial value as food supplements and
      medical materials. Moreover, these enzymes have attracted much attention from
      scientists because they have potential in tailored synthesis of alpha-glucans
      with desired structures and properties. Although more and more GSs have been
      characterized, the origin and evolution of these enzymes have not been well
      addressed. This study describes a GS with the appearance of a BrS (i.e., high
      levels of similarity to BrSs in sequence analysis). Further analysis indicated
      that this enzyme synthesized a type of insoluble glucan composed of an alpha-(1
      >6) glucosidic backbone and many alpha-(1->4)- and alpha-(1->3)-linked branches,
      the linkage composition of which has rarely been reported in the literature. This
      BrS-like GS enzyme might be an evolutionary intermediate between BrS and GS
      enzymes.

PMID- 29453262
TI  - Insights into the fundamental physiology of the uncultured Fe-oxidizing bacterium
      Leptothrix ochracea.
AB  - Leptothrix ochracea is known for producing large volumes of iron-oxyhydroxide
      sheaths that alter wetland biogeochemistry. For over a century, these delicate
      structures have fascinated microbiologists and geoscientists. Because L. ochracea
      still resists long-term in vitro culture, the debate regarding its metabolic
      classification dates back to 1885. We developed a novel culturing technique for
      L. ochracea using in situ natural waters, and coupled this with single cell
      genomics and nanoscale secondary ion mass spectrophotometry (nanoSIMS) to probe
      L. ochracea's physiology. In micro-slide cultures L. ochracea doubled every 5.7
      hrs, had an absolute growth requirement for ferrous iron, had the genomic
      capacity for iron-oxidation, and a branched electron transport chain with
      cytochromes putatively involved in lithotrophic iron-oxidation. Additionally, its
      genome encoded several electron transport chain proteins including, a
      molybdopterin ACIII complex, a cytochrome bd oxidase reductase, and several
      terminal oxidase genes. L. ochracea contained two key autotrophic proteins in the
      Calvin Benson Bassham cycle, a Form II ribulose-bis-phosphate carboxylase and a
      phosphoribulose kinase. L. ochracea also assimilated bicarbonate, although
      calculations suggest bicarbonate assimilation is a small fraction of its total
      carbon assimilation. Finally, L. ochracea's fundamental physiology is a hybrid of
      the chemolithotrophic Gallionella-type iron-oxidizing bacteria and the sheathed,
      heterotrophic filamentous metal-oxidizing bacteria of the Leptothrix-Sphaerotilus
      genera. This allows L. ochracea to inhabit a unique niche within the neutrophilic
      iron seeps.ImportanceLeptothrix ochracea was one of three groups of organisms
      Sergei Winogradsky used in the 1880s to develop the hypothesis on
      chemolithotrophy. L. ochracea continues to resist cultivation and appears to have
      an absolute requirement for organic rich waters suggesting its true physiology
      remains unknown. Further, L. ochracea is an ecological engineer, a few L.
      ochracea cells can generate prodigious volumes of iron-oxyhydroxides changing the
      ecosystem geochemistry and ecology. Therefore, to determine Lochracea's basic
      physiology, we employed new single-cell techniques to demonstrate: L. ochracea
      oxidizes iron to generate energy and, despite predicted genes for autotrophic
      growth, L. ochacea assimilates a fraction of the total CO2 that autotrophs do.
      Although not a true chemolithoautotroph, L. ochracea's physiological strategy
      allows it to be flexible, extensively colonize iron-rich wetlands.

PMID- 29453263
TI  - Enzyme Activities of Two Recombinant Heme-Containing Peroxidases, TvDyP1 and
      TvVP2, Identified from the Secretome of Trametes versicolor.
AB  - Trametesversicolor is a wood-inhabiting agaricomycete known for its ability to
      cause strong white-rot decay on hardwood and for its high tolerance of phenolic
      compounds. The goal of the present work was to gain insights into the molecular
      biology and biochemistry of the heme-including class II and dye-decolorizing
      peroxidases secreted by this fungus. Proteomic analysis of the secretome of T.
      versicolor BRFM 1218 grown on oak wood revealed a set of 200 secreted proteins,
      among which were the dye-decolorizing peroxidase TvDyP1 and the versatile
      peroxidase TvVP2. Both peroxidases were heterologously produced in Escherichia
      coli, biochemically characterized, and tested for the ability to oxidize complex
      substrates. Both peroxidases were found to be active against several substrates
      under acidic conditions, and TvDyP1 was very stable over a relatively large pH
      range of 2.0 to 6.0, while TvVP2 was more stable at pH 5.0 to 6.0 only. The
      thermostability of both enzymes was also tested, and TvDyP1 was globally found to
      be more stable than TvVP2. After 180 min of incubation at temperatures ranging
      from 30 to 50 degrees C, the activity of TvVP2 drastically decreased, with 10 to
      30% of the initial activity retained. Under the same conditions, TvDyP1 retained
      20 to 80% of its enzyme activity. The two proteins were catalytically
      characterized, and TvVP2 was shown to accept a wider range of reducing substrates
      than TvDyP1. Furthermore, both enzymes were found to be active against two
      flavonoids, quercetin and catechin, found in oak wood, with TvVP2 displaying more
      rapid oxidation of the two compounds. They were tested for the ability to
      decolorize five industrial dyes, and TvVP2 presented a greater ability to oxidize
      and decolorize the dye substrates than TvDyP1.IMPORTANCETrametesversicolor is a
      wood-inhabiting agaricomycete known for its ability to cause strong white-rot
      decay on hardwood and for its high tolerance of phenolic compounds. Among white
      rot fungi, the basidiomycete T. versicolor has been extensively studied for its
      ability to degrade wood, specifically lignin, thanks to an extracellular
      oxidative enzymatic system. The corresponding oxidative system was previously
      studied in several works for classical lignin and manganese peroxidases, and in
      this study, two new components of the oxidative system of T. versicolor, one dye
      decolorizing peroxidase and one versatile peroxidase, were biochemically
      characterized in depth and compared to other fungal peroxidases.

PMID- 29453264
TI  - Bacterial Community Shift and Coexisting/Coexcluding Patterns Revealed by Network
      Analysis in a Uranium-Contaminated Site after Bioreduction Followed by
      Reoxidation.
AB  - A site in Oak Ridge, TN, USA, has sediments that contain >3% iron oxides and is
      contaminated with uranium (U). The U(VI) was bioreduced to U(IV) and immobilized
      in situ through intermittent injections of ethanol. It then was allowed to
      reoxidize via the invasion of low-pH (3.6 to 4.0), high-nitrate (up to 200 mM)
      groundwater back into the reduced zone for 1,383 days. To examine the
      biogeochemical response, high-throughput sequencing and network analysis were
      applied to characterize bacterial population shifts, as well as cooccurrence and
      coexclusion patterns among microbial communities. A paired t test indicated no
      significant changes of alpha-diversity for the bioactive wells. However, both
      nonmetric multidimensional scaling and analysis of similarity confirmed a
      significant distinction in the overall composition of the bacterial communities
      between the bioreduced and the reoxidized sediments. The top 20 major genera
      accounted for >70% of the cumulative contribution to the dissimilarity in the
      bacterial communities before and after the groundwater invasion. Castellaniella
      had the largest dissimilarity contribution (17.7%). For the bioactive wells, the
      abundance of the U(VI)-reducing genera Geothrix, Desulfovibrio, Ferribacterium,
      and Geobacter decreased significantly, whereas the denitrifying Acidovorax
      abundance increased significantly after groundwater invasion. Additionally, seven
      genera, i.e., Castellaniella, Ignavibacterium, Simplicispira, Rhizomicrobium,
      Acidobacteria Gp1, Acidobacteria Gp14, and Acidobacteria Gp23, were significant
      indicators of bioactive wells in the reoxidation stage. Canonical correspondence
      analysis indicated that nitrate, manganese, and pH affected mostly the U(VI)
      reducing genera and indicator genera. Cooccurrence patterns among microbial taxa
      suggested the presence of taxa sharing similar ecological niches or
      mutualism/commensalism/synergism interactions.IMPORTANCE High-throughput
      sequencing technology in combination with a network analysis approach were used
      to investigate the stabilization of uranium and the corresponding dynamics of
      bacterial communities under field conditions with regard to the heterogeneity and
      complexity of the subsurface over the long term. The study also examined
      diversity and microbial community composition shift, the common genera, and
      indicator genera before and after long-term contaminated-groundwater invasion and
      the relationship between the target functional community structure and
      environmental factors. Additionally, deciphering cooccurrence and coexclusion
      patterns among microbial taxa and environmental parameters could help predict
      potential biotic interactions (cooperation/competition), shared physiologies, or
      habitat affinities, thus, improving our understanding of ecological niches
      occupied by certain specific species. These findings offer new insights into
      compositions of and associations among bacterial communities and serve as a
      foundation for future bioreduction implementation and monitoring efforts applied
      to uranium-contaminated sites.

PMID- 29453265
TI  - Integrated Metabolomics and Morphogenesis Reveal Volatile Signaling of the
      Nematode-Trapping Fungus Arthrobotrys oligospora.
AB  - The adjustment of metabolic patterns is fundamental to fungal biology and plays
      vital roles in adaptation to diverse ecological challenges. Nematode-trapping
      fungi can switch their lifestyle from saprophytic to pathogenic by developing
      specific trapping devices induced by nematodes to infect their prey as a response
      to nutrient depletion in nature. However, the chemical identity of the specific
      fungal metabolites used during the switch remains poorly understood. We
      hypothesized that these important signal molecules might be volatile in nature.
      Gas chromatography-mass spectrometry was used to carry out comparative analysis
      of fungal metabolomics during the saprophytic and pathogenic lifestyles of the
      model species Arthrobotrys oligospora Two media commonly used in research on this
      species, cornmeal agar (CMA) and potato dextrose agar (PDA), were chosen for use
      in this study. The fungus produced a small group of volatile furanone and pyrone
      metabolites that were associated with the switch from the saprophytic to the
      pathogenic stage. A. oligospora fungi grown on CMA tended to produce more traps
      and employ attractive furanones to improve the utilization of traps, while fungi
      grown on PDA developed fewer traps and used nematode-toxic furanone metabolites
      to compensate for insufficient traps. Another volatile pyrone metabolite, maltol,
      was identified as a morphological regulator for enhancing trap formation.
      Deletion of the gene AOL_s00079g496 in A. oligospora led to increased amounts of
      the furanone attractant (2-fold) in mutants and enhanced the attractive activity
      (1.5-fold) of the fungus, while it resulted in decreased trap formation. This
      investigation provides new insights regarding the comprehensive tactics of fungal
      adaptation to environmental stress, integrating both morphological and
      metabolomic mechanisms.IMPORTANCE Nematode-trapping fungi are a unique group of
      soil-living fungi that can switch from the saprophytic to the pathogenic
      lifestyle once they come into contact with nematodes as a response to nutrient
      depletion. In this study, we investigated the metabolic response during the
      switch and the key types of metabolites involved in the interaction between fungi
      and nematodes. Our findings indicate that A. oligospora develops multiple and
      flexible metabolic tactics corresponding to different morphological responses to
      nematodes. A. oligospora can use similar volatile furanone and pyrone metabolites
      with different ecological functions to help capture nematodes in the fungal
      switch from the saprophytic to the pathogenic lifestyle. Furthermore, studies
      with A. oligospora mutants with increased furanone and pyrone metabolites
      confirmed the results. This investigation reveals the importance of volatile
      signaling in the comprehensive tactics used by nematode-trapping fungi,
      integrating both morphological and metabolomic mechanisms.

PMID- 29453266
TI  - The Gills of Reef Fish Support a Distinct Microbiome Influenced by Host-Specific
      Factors.
AB  - Teleost fish represent the most diverse of the vertebrate groups and play
      important roles in food webs, as ecosystem engineers, and as vectors for
      microorganisms. However, the microbial ecology of fishes remains underexplored
      for most host taxa and for certain niches on the fish body. This is particularly
      true for the gills, the key sites of respiration and waste exchange in fishes.
      Here we provide a comprehensive analysis of the gill microbiome. We focus on
      ecologically diverse taxa from coral reefs around Moorea, sampling the gills and
      intestines of adults and juveniles representing 15 families. The gill microbiome
      composition differed significantly from that of the gut for both adults and
      juveniles, with fish-associated niches having lower alpha diversity values and
      higher beta diversity values than those for seawater, sediment, and alga
      associated microbiomes. Of ~45,000 operational taxonomic units (OTUs) detected
      across all samples, 11% and 13% were detected only in the gill and the intestine,
      respectively. OTUs most enriched in the gill included members of the
      gammaproteobacterial genus Shewanella and the family Endozoicimonaceae In adult
      fish, both gill and intestinal microbiomes varied significantly among host
      species grouped by diet category. Gill and intestinal microbiomes from the same
      individual were more similar to one another than to gill and intestinal
      microbiomes from different individuals. These results demonstrate that distinct
      body sites are jointly influenced by host-specific organizing factors operating
      at the level of the host individual. The results also identify taxonomic
      signatures unique to the gill and the intestine, confirming fish-associated
      niches as distinct reservoirs of marine microbial diversity.IMPORTANCE Fish
      breathe and excrete waste through their gills. The gills are also potential sites
      of pathogen invasion and colonization by other microbes. However, we know little
      about the microbial communities that live on the gill and the factors shaping
      their diversity. Focusing on ecologically distinct types of coral reef fish, we
      provide a comprehensive analysis of the fish gill microbiome. By comparison to
      microbiomes of the gut and the surrounding environment, we identify microbes
      unique to the gill niche. These microbes may be targets for further studies to
      determine the contribution of the microbiome to waste exchange or host immunity.
      We also show that despite exhibiting a unique taxonomic signature, the gill
      microbiome is influenced by factors that also influence the gut microbiome. These
      factors include the specific identity of the host individual. These results
      suggest basic principles describing how association with fishes structures the
      composition of microbial communities.

PMID- 29453267
TI  - Plant-Microbe and Abiotic Factors Influencing Salmonella Survival and Growth on
      Alfalfa Sprouts and Swiss Chard Microgreens.
AB  - Microgreens, like sprouts, are relatively fast-growing products and are generally
      consumed raw. Moreover, as observed for sprouts, microbial contamination from
      preharvest sources may also be present in the production of microgreens. In this
      study, two Salmonella enterica serovars (Hartford and Cubana), applied at
      multiple inoculation levels, were evaluated for survival and growth on alfalfa
      sprouts and Swiss chard microgreens by using the most-probable-number (MPN)
      method. Various abiotic factors were also examined for their effects on
      Salmonella survival and growth on sprouts and microgreens. Community-level
      physiological profiles (CLPPs) of sprout/microgreen rhizospheres with different
      levels of S. enterica inoculation at different growth stages were characterized
      by use of Biolog EcoPlates. In the seed contamination group, the ability of S.
      enterica to grow on sprouting alfalfa seeds was affected by both seed storage
      time and inoculation level but not by serovar. However, the growth of S. enterica
      on Swiss chard microgreens was affected by serovar and inoculation level. Seed
      storage time had little effect on the average level of Salmonella populations in
      microgreens. In the irrigation water contamination group, the growth of
      Salmonella on both alfalfa sprouts and microgreens was largely affected by
      inoculation level. Surprisingly, the growth medium was found to play an important
      role in Salmonella survival and growth on microgreens. CLPP analysis showed
      significant changes in the microbial community metabolic diversity during
      sprouting for alfalfa sprouts, but few temporal changes were seen with
      microgreens. The data suggest that the change in rhizosphere bacterial functional
      diversity was dependent on the host but independent of Salmonella
      contamination.IMPORTANCE Sprouts and microgreens are considered "functional
      foods," i.e., foods containing health-promoting or disease-preventing properties
      in addition to normal nutritional values. However, the microbial risk associated
      with microgreens has not been well studied. This study evaluated Salmonella
      survival and growth on microgreens compared to those on sprouts, as well as other
      abiotic factors that could affect Salmonella survival and growth on microgreens.
      This work provides baseline data for risk assessment of microbial contamination
      of sprouts and microgreens. Understanding the risks of Salmonella contamination
      and its effects on rhizosphere microbial communities enables a better
      understanding of host-pathogen dynamics in sprouts and microgreens. The data also
      contribute to innovative preventive control strategies for Salmonella
      contamination of sprouts and microgreens.

PMID- 29453270
TI  - Retraction: Effect of acupuncture and Chinese herbal medicine on subacute stroke
      outcomes: a single center randomized controlled trial.

PMID- 29453268
TI  - High Microbial Diversity Promotes Soil Ecosystem Functioning.
AB  - In soil, the link between microbial diversity and carbon transformations is
      challenged by the concept of functional redundancy. Here, we hypothesized that
      functional redundancy may decrease with increasing carbon source recalcitrance
      and that coupling of diversity with C cycling may change accordingly. We
      manipulated microbial diversity to examine how diversity decrease affects the
      decomposition of easily degradable (i.e., allochthonous plant residues) versus
      recalcitrant (i.e., autochthonous organic matter) C sources. We found that a
      decrease in microbial diversity (i) affected the decomposition of both
      autochthonous and allochthonous carbon sources, thereby reducing global CO2
      emission by up to 40%, and (ii) shaped the source of CO2 emission toward
      preferential decomposition of most degradable C sources. Our results also
      revealed that the significance of the diversity effect increases with nutrient
      availability. Altogether, these findings show that C cycling in soil may be more
      vulnerable to microbial diversity changes than expected from previous studies,
      particularly in ecosystems exposed to nutrient inputs. Thus, concern about the
      preservation of microbial diversity may be highly relevant in the current global
      change context assumed to impact soil biodiversity and the pulse inputs of plant
      residues and rhizodeposits into the soil.IMPORTANCE With hundreds of thousands of
      taxa per gram of soil, microbial diversity dominates soil biodiversity. While
      numerous studies have established that microbial communities respond rapidly to
      environmental changes, the relationship between microbial diversity and soil
      functioning remains controversial. Using a well-controlled laboratory approach,
      we provide empirical evidence that microbial diversity may be of high
      significance for organic matter decomposition, a major process on which rely many
      of the ecosystem services provided by the soil ecosystem. These new findings
      should be taken into account in future studies aimed at understanding and
      predicting the functional consequences of changes in microbial diversity on soil
      ecosystem services and carbon storage in soil.

PMID- 29453271
TI  - Government will cap legal costs of clinical negligence claims.

PMID- 29453272
TI  - Building the Child Safety Collaborative Innovation and Improvement Network: How
      does it work and what is it achieving?
AB  - OBJECTIVE: This study investigated whether the Child Safety Collaborative
      Innovation and Improvement Network (CS CoIIN) framework could be applied in the
      field of injury and violence prevention to reduce fatalities, hospitalizations
      and emergency department visits among 0-19 year olds. SAMPLE: Twenty-one
      states/jurisdictions were accepted into cohort 1 of the CS CoIIN, and 14 were
      engaged from March 2016 through April 2017. A quality improvement framework was
      used to test, implement and spread evidence-based change ideas (strategies and
      programs) in child passenger safety, falls prevention, interpersonal violence
      prevention, suicide and self-harm prevention and teen driver safety. PROCEDURES:
      Outcome and process measure data were analyzed using run chart rules. Descriptive
      data were analyzed for participation measures and descriptive statistics were
      produced. Qualitative data were analyzed to identify key themes. RESULTS: Seventy
      six percent of CS CoIIN states/jurisdictions were engaged in activities and used
      data to inform decision making. Within a year, states/jurisdictions were able to
      test and implement evidence-based change ideas in pilot sites. A small group
      showed improvement in process measures and were ready to spread change ideas.
      Improvement in outcome measures was not achieved; however, 25% of
      states/jurisdictions identified data sources and reported on real-time outcome
      measures. CONCLUSIONS: Evidence indicates the CS CoIIN framework can be applied
      to make progress on process measures, but more time is needed to determine if
      this will result in progress on long-term outcome measures of fatalities,
      hospitalizations and emergency department visits. Seventeen states/jurisdictions
      will participate in cohort 2.

PMID- 29453273
TI  - Evolution of a holistic systems approach to planning and managing road safety:
      the Victorian case study, 1970-2015.
AB  - BACKGROUND: The Victorian Safe System approach to road safety slowly evolved from
      a combination of the Swedish Vision Zero philosophy and the Sustainable Safety
      model developed by the Dutch. The Safe System approach reframes the way in which
      road safety is viewed and managed. METHODS: This paper presents a case study of
      the institutional change required to underpin the transformation to a holistic
      approach to planning and managing road safety in Victoria, Australia. RESULTS:
      The adoption and implementation of a Safe System approach require strong
      institutional leadership and close cooperation among all the key agencies
      involved, and Victoria was fortunate in that it had a long history of strong
      interagency mechanisms in place. However, the challenges in the implementation of
      the Safe System strategy in Victoria are generally neither technical nor
      scientific; they are predominantly social and political. While many governments
      purport to develop strategies based on Safe System thinking, on-the-ground action
      still very much depends on what politicians perceive to be publicly acceptable,
      and Victoria is no exception. CONCLUSIONS: This is a case study of the complexity
      of institutional change and is presented in the hope that the lessons may prove
      useful for others seeking to adopt more holistic planning and management of road
      safety. There is still much work to be done in Victoria, but the institutional
      cultural shift has taken root. Ongoing efforts must be continued to achieve alert
      and compliant road users; however, major underpinning benefits will be achieved
      through focusing on road network safety improvements (achieving forgiving
      infrastructure, such as wire rope barriers) in conjunction with reviews of posted
      speed limits (to be set in response to the level of protection offered by the
      road infrastructure) and by the progressive introduction into the fleet of modern
      vehicle safety features.

PMID- 29453274
TI  - Select and resequence reveals relative fitness of bacteria in symbiotic and free
      living environments.
AB  - Assays to accurately estimate relative fitness of bacteria growing in multistrain
      communities can advance our understanding of how selection shapes diversity
      within a lineage. Here, we present a variant of the "evolve and resequence"
      approach both to estimate relative fitness and to identify genetic variants
      responsible for fitness variation of symbiotic bacteria in free-living and host
      environments. We demonstrate the utility of this approach by characterizing
      selection by two plant hosts and in two free-living environments (sterilized soil
      and liquid media) acting on synthetic communities of the facultatively symbiotic
      bacterium Ensifer meliloti We find (i) selection that hosts exert on rhizobial
      communities depends on competition among strains, (ii) selection is stronger
      inside hosts than in either free-living environment, and (iii) a positive host
      dependent relationship between relative strain fitness in multistrain communities
      and host benefits provided by strains in single-strain experiments. The greatest
      changes in allele frequencies in response to plant hosts are in genes associated
      with motility, regulation of nitrogen fixation, and host/rhizobia signaling. The
      approach we present provides a powerful complement to experimental evolution and
      forward genetic screens for characterizing selection in bacterial populations,
      identifying gene function, and surveying the functional importance of naturally
      occurring genomic variation.

PMID- 29453275
TI  - Structure-based discovery of selective positive allosteric modulators of
      antagonists for the M2 muscarinic acetylcholine receptor.
AB  - Subtype-selective antagonists for muscarinic acetylcholine receptors (mAChRs)
      have long been elusive, owing to the highly conserved orthosteric binding site.
      However, allosteric sites of these receptors are less conserved, motivating the
      search for allosteric ligands that modulate agonists or antagonists to confer
      subtype selectivity. Accordingly, a 4.6 million-molecule library was docked
      against the structure of the prototypical M2 mAChR, seeking molecules that
      specifically stabilized antagonist binding. This led us to identify a positive
      allosteric modulator (PAM) that potentiated the antagonist N-methyl scopolamine
      (NMS). Structure-based optimization led to compound '628, which enhanced binding
      of NMS, and the drug scopolamine itself, with a cooperativity factor (alpha) of
      5.5 and a KB of 1.1 MUM, while sparing the endogenous agonist acetylcholine. NMR
      spectral changes determined for methionine residues reflected changes in the
      allosteric network. Moreover, '628 slowed the dissociation rate of NMS from the
      M2 mAChR by 50-fold, an effect not observed at the other four mAChR subtypes. The
      specific PAM effect of '628 on NMS antagonism was conserved in functional assays,
      including agonist stimulation of [35S]GTPgammaS binding and ERK 1/2
      phosphorylation. Importantly, the selective allostery between '628 and NMS was
      retained in membranes from adult rat hypothalamus and in neonatal rat
      cardiomyocytes, supporting the physiological relevance of this PAM/antagonist
      approach. This study supports the feasibility of discovering PAMs that confer
      subtype selectivity to antagonists; molecules like '628 can convert an
      armamentarium of potent but nonselective GPCR antagonist drugs into subtype
      selective reagents, thus reducing their off-target effects.

PMID- 29453276
TI  - Entropy drives selective fluorine recognition in the fluoroacetyl-CoA
      thioesterase from Streptomyces cattleya.
AB  - Fluorinated small molecules play an important role in the design of bioactive
      compounds for a broad range of applications. As such, there is strong interest in
      developing a deeper understanding of how fluorine affects the interaction of
      these ligands with their targets. Given the small number of fluorinated
      metabolites identified to date, insights into fluorine recognition have been
      provided almost entirely by synthetic systems. The fluoroacetyl-CoA thioesterase
      (FlK) from Streptomyces cattleya thus provides a unique opportunity to study an
      enzyme-ligand pair that has been evolutionarily optimized for a surprisingly high
      106 selectivity for a single fluorine substituent. In these studies, we
      synthesize a series of analogs of fluoroacetyl-CoA and acetyl-CoA to generate
      nonhydrolyzable ester, amide, and ketone congeners of the thioester substrate to
      isolate the role of fluorine molecular recognition in FlK selectivity. Using a
      combination of thermodynamic, kinetic, and protein NMR experiments, we show that
      fluorine recognition is entropically driven by the interaction of the fluorine
      substituent with a key residue, Phe-36, on the lid structure that covers the
      active site, resulting in an ~5- to 20-fold difference in binding (KD). Although
      the magnitude of discrimination is similar to that found in designed synthetic
      ligand-protein complexes where dipolar interactions control fluorine recognition,
      these studies show that hydrophobic and solvation effects serve as the major
      determinant of naturally evolved fluorine selectivity.

PMID- 29453277
TI  - Editing out five Serpina1 paralogs to create a mouse model of genetic emphysema.
AB  - Chronic obstructive pulmonary disease affects 10% of the worldwide population,
      and the leading genetic cause is alpha-1 antitrypsin (AAT) deficiency. Due to the
      complexity of the murine locus, which includes up to six Serpina1 paralogs, no
      genetic animal model of the disease has been successfully generated until now.
      Here we create a quintuple Serpina1a-e knockout using CRISPR/Cas9-mediated genome
      editing. The phenotype recapitulates the human disease phenotype, i.e., absence
      of hepatic and circulating AAT translates functionally to a reduced capacity to
      inhibit neutrophil elastase. With age, Serpina1 null mice develop emphysema
      spontaneously, which can be induced in younger mice by a lipopolysaccharide
      challenge. This mouse models not only AAT deficiency but also emphysema and is a
      relevant genetic model and not one based on developmental impairment of
      alveolarization or elastase administration. We anticipate that this unique model
      will be highly relevant not only to the preclinical development of therapeutics
      for AAT deficiency, but also to emphysema and smoking research.

PMID- 29453278
TI  - Molecular signatures of circulating melanoma cells for monitoring early response
      to immune checkpoint therapy.
AB  - A subset of patients with metastatic melanoma have sustained remissions following
      treatment with immune checkpoint inhibitors. However, analyses of pretreatment
      tumor biopsies for markers predictive of response, including PD-1 ligand (PD-L1)
      expression and mutational burden, are insufficiently precise to guide treatment
      selection, and clinical radiographic evidence of response on therapy may be
      delayed, leading to some patients receiving potentially ineffective but toxic
      therapy. Here, we developed a molecular signature of melanoma circulating tumor
      cells (CTCs) to quantify early tumor response using blood-based monitoring. A
      quantitative 19-gene digital RNA signature (CTC score) applied to
      microfluidically enriched CTCs robustly distinguishes melanoma cells, within a
      background of blood cells in reconstituted and in patient-derived (n = 42) blood
      specimens. In a prospective cohort of 49 patients treated with immune checkpoint
      inhibitors, a decrease in CTC score within 7 weeks of therapy correlates with
      marked improvement in progression-free survival [hazard ratio (HR), 0.17; P =
      0.008] and overall survival (HR, 0.12; P = 0.04). Thus, digital quantitation of
      melanoma CTC-derived transcripts enables serial noninvasive monitoring of tumor
      burden, supporting the rational application of immune checkpoint inhibition
      therapies.

PMID- 29453280
TI  - Elevated Expression of IL-33 and TSLP in the Airways of Human Asthmatics In Vivo:
      A Potential Biomarker of Severe Refractory Disease.
AB  - The epithelial cytokines IL-33, thymic stromal lymphopoietin (TSLP), and IL-25
      have been implicated in asthma pathogenesis because they promote Th2-type
      cytokine synthesis, but their expression is relatively poorly documented in "real
      life" human asthma. Using bronchoalveolar lavage fluid (BALF), we measured airway
      concentrations of these mediators and compared them with those of Th1- and Th2
      type cytokines, airway infiltration of neutrophils and eosinophils, and lung
      function in a large group of asthmatic patients with a range of disease severity
      (n = 70) and control subjects (n = 30). The median BALF concentrations of IL-33,
      TSLP, IL-4, IL-5, IL-13, and IL-12p70, but not IL-25, IL-2, or IFN-gamma, were
      significantly elevated in asthmatics compared with controls (p < 0.05). The
      concentrations of IL-33 and TSLP, but not IL-25, correlated inversely with the
      lung function (forced expiratory volume in the first second) of asthmatics (IL
      33: r = -0.488, p < 0.0001; TSLP: r = -0.565, p < 0.0001) independently of
      corticosteroid therapy. When divided according to disease severity and
      corticosteroid therapy, all subgroups of asthmatics had elevated median numbers
      of eosinophils in BALF, whereas the patients with more severe disease who were
      treated with corticosteroids had higher numbers of neutrophils compared with
      milder asthmatics not so treated and control subjects (p < 0.05). The data
      implicate TSLP and IL-33 in the pathogenesis of asthma that is characterized by
      persistent airway inflammation and impaired lung function despite intensive
      corticosteroid therapy, highlighting them as potential molecular targets.

PMID- 29453279
TI  - IL-12+IL-18 Cosignaling in Human Macrophages and Lung Epithelial Cells Activates
      Cathelicidin and Autophagy, Inhibiting Intracellular Mycobacterial Growth.
AB  - The ability of Mycobacterium tuberculosis to block host antimicrobial responses
      in infected cells provides a key mechanism for disease pathogenesis. The immune
      system has evolved to overcome this blockade to restrict the infection, but it is
      not clear whether two key innate cytokines (IL-12/IL-18) involved in host defense
      can enhance antimycobacterial mechanisms. In this study, we demonstrated that the
      combination of IL-12 and IL-18 triggered an antimicrobial response against
      mycobacteria in infected macrophages (THP-1 and human primary monocyte-derived
      macrophages) and pulmonary epithelial A549 cells. The inhibition of intracellular
      bacterial growth required p38-MAPK and STAT4 pathways, the vitamin D receptor,
      the vitamin D receptor-derived antimicrobial peptide cathelicidin, and autophagy,
      but not caspase-mediated apoptosis. Finally, the ability of IL-12+IL-18 to
      activate an innate antimicrobial response in human primary macrophages was
      dependent on the autonomous production of IFN-gamma and the CAMP/autophagy
      pathway. Together, these data suggest that IL-12+IL-18 cosignaling can trigger
      the antimicrobial protein cathelicidin and autophagy, resulting in inhibition of
      intracellular mycobacteria in macrophages and lung epithelial cells.

PMID- 29453281
TI  - The PI3Kdelta-Selective Inhibitor Idelalisib Minimally Interferes with Immune
      Effector Function Mediated by Rituximab or Obinutuzumab and Significantly
      Augments B Cell Depletion In Vivo.
AB  - Idelalisib is a highly selective oral inhibitor of PI3Kdelta indicated for the
      treatment of patients with relapsed chronic lymphocytic leukemia in combination
      with rituximab. Despite additive clinical effects, previous studies have
      paradoxically demonstrated that targeted therapies potentially negatively affect
      anti-CD20 mAb effector mechanisms. To address these potential effects, we
      investigated the impact of PI3Kdelta inhibition by idelalisib on the effector
      mechanisms of rituximab and obinutuzumab. At clinically relevant concentrations,
      idelalisib minimally influenced rituximab- and obinutuzumab-mediated Ab-dependent
      cellular cytotoxicity and phagocytosis on human lymphoma cell lines, while
      maintaining the superiority of obinutuzumab-mediated Ab-dependent cellular
      cytotoxicity. Consistent with this, idelalisib did not influence obinutuzumab
      mediated B cell depletion in whole-blood B cell-depletion assays. Further,
      idelalisib significantly enhanced obinutuzumab-mediated direct cell death of
      chronic lymphocytic leukemia cells. In murine systems, in vivo inhibition of
      PI3Kdelta minimally interfered with maximal rituximab- or obinutuzumab-mediated
      depletion of leukemic targets. In addition, the duration of rituximab- and
      obinutuzumab-mediated depletion of leukemia cells was extended by combination
      with PI3Kdelta inhibition. Collectively, these data demonstrate that PI3Kdelta
      inhibition does not significantly affect the effector mechanisms induced by
      rituximab or obinutuzumab and provides an effective in vivo therapeutic
      combination. Therefore, combinations of obinutuzumab and idelalisib are currently
      being assessed in clinical studies.

PMID- 29453282
TI  - Eukaryotic translation elongation factor 2 (eEF2) catalyzes reverse translocation
      of the eukaryotic ribosome.
AB  - During protein synthesis, a ribosome moves along the mRNA template and, using
      aminoacyl-tRNAs, decodes the template nucleotide triplets to assemble a protein
      amino acid sequence. This movement is accompanied by shifting of mRNA-tRNA
      complexes within the ribosome in a process called translocation. In living cells,
      this process proceeds in a unidirectional manner, bringing the ribosome to the 3'
      end of mRNA, and is catalyzed by the GTPase translation elongation factor 2 (EF-G
      in prokaryotes and eEF2 in eukaryotes). Interestingly, the possibility of
      spontaneous backward translocation has been shown in vitro for bacterial
      ribosomes, suggesting a potential reversibility of this reaction. However, this
      possibility has not yet been tested for eukaryotic ribosomes. Here, using a
      reconstituted mammalian translation system, we show that the eukaryotic
      elongation factor eEF2 catalyzes ribosomal reverse translocation at one mRNA
      triplet. We found that this process requires a cognate tRNA in the ribosomal E
      site and cannot occur spontaneously without eEF2. The efficiency of this reaction
      depended on the concentrations of eEF2 and cognate tRNAs and increased in the
      presence of nonhydrolyzable GTP analogues. Of note, ADP-ribosylation of eEF2
      domain IV blocked reverse translocation, suggesting a crucial role of
      interactions of this domain with the ribosome for the catalysis of the reaction.
      In summary, our findings indicate that eEF2 is able to induce ribosomal
      translocation in forward and backward directions, highlighting the universal
      mechanism of tRNA-mRNA movements within the ribosome.

PMID- 29453283
TI  - Chemical stresses fail to mimic the unfolded protein response resulting from
      luminal load with unfolded polypeptides.
AB  - The stress sensors ATF6, IRE1, and PERK monitor deviations from homeostatic
      conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of
      eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to re
      establish proteostasis. UPR have been extensively investigated in cells exposed
      to chemicals that activate ER stress sensors by perturbing calcium, N-glycans, or
      redox homeostasis. Cell responses to variations in luminal load with unfolded
      proteins are, in contrast, poorly characterized. Here, we compared gene and
      protein expression profiles in HEK293 cells challenged with ER stress-inducing
      drugs or expressing model polypeptides. Drug titration to limit up-regulation of
      the endogenous ER stress reporters heat shock protein family A (Hsp70) member 5
      (BiP/HSPA5) and homocysteine-inducible ER protein with ubiquitin-like domain 1
      (HERP/HERPUD1) to levels comparable with luminal accumulation of unfolded
      proteins substantially reduced the amplitude of both transcriptional and
      translational responses. However, these drug-induced changes remained pleiotropic
      and failed to recapitulate responses to ER load with unfolded proteins. These
      required unfolded protein association with BiP and induced a much smaller subset
      of genes participating in a chaperone complex that binds unfolded peptide chains.
      In conclusion, UPR resulting from ER load with unfolded proteins proceed via a
      well-defined and fine-tuned pathway, whereas even mild chemical stresses caused
      by compounds often used to stimulate UPR induce cellular responses largely
      unrelated to the UPR or ER-mediated protein secretion.

PMID- 29453284
TI  - Structural and compositional diversity of fibrillin microfibrils in human
      tissues.
AB  - Elastic fibers comprising fibrillin microfibrils and elastin are present in many
      tissues, including the skin, lungs, and arteries, where they confer elasticity
      and resilience. Although fibrillin microfibrils play distinct and tissue-specific
      functional roles, it is unclear whether their ultrastructure and composition
      differ between elastin-rich (skin) and elastin-poor (ciliary body and zonule)
      organs or after in vitro synthesis by cultured cells. Here, we used atomic force
      microscopy, which revealed that the bead morphology of fibrillin microfibrils
      isolated from the human eye differs from those isolated from the skin. Using
      newly developed pre-MS preparation methods and LC-MS/MS, we detected tissue
      specific regions of the fibrillin-1 primary structure that were differentially
      susceptible to proteolytic extraction. Comparing tissue- and culture-derived
      microfibrils, we found that dermis- and dermal fibroblast-derived fibrillin
      microfibrils differ in both bead morphology and periodicity and also exhibit
      regional differences in fibrillin-1 proteolytic susceptibility. In contrast,
      collagen VI microfibrils from the same dermal or fibroblast samples were
      invariant in ultrastructure (periodicity) and protease susceptibility. Finally,
      we observed that skin- and eye-derived microfibril suspensions were enriched in
      elastic fiber- and basement membrane-associated proteins, respectively. LC-MS/MS
      also identified proteins (such as calreticulin and protein-disulfide isomerase)
      that are potentially fundamental to fibrillin microfibril biology, regardless of
      their tissue source. Fibrillin microfibrils synthesized in cell culture lacked
      some of these key proteins (MFAP2 and -4 and fibrillin-2). These results showcase
      the structural diversity of these key extracellular matrix assemblies, which may
      relate to their distinct roles in the tissues where they reside.

PMID- 29453285
TI  - The distal upstream region of insulin-like growth factor-binding protein-1
      enhances its expression in endometrial stromal cells during decidualization.
AB  - We have previously shown that decidualization of human endometrial stromal cells
      (ESCs) causes a genome-wide increase in the levels of acetylation of histone-H3
      Lys-27 (H3K27ac). We also reported that the distal gene regions, more than 3 kb
      up- or downstream of gene transcription start sites have increased H3K27ac
      levels. Insulin-like growth factor-binding protein-1 (IGFBP-1) is a specific
      decidualization marker and has increased H3K27ac levels in its distal upstream
      region (-4701 to -7501 bp). Here, using a luciferase reporter gene construct
      containing this IGFBP-1 upstream region, we tested the hypothesis that it is an
      IGFBP-1 enhancer. To induce decidualization, we incubated ESCs with cAMP and
      found that cAMP increased luciferase expression, indicating that decidualization
      increased the transcriptional activity from the IGFBP-1 upstream region.
      Furthermore, CRISPR/Cas9-mediated deletion of this region in HepG2 cells
      significantly reduced IGFBP-1 expression, confirming its role as an IGFBP-1
      enhancer. A ChIP assay revealed that cAMP increased the recruitment of the
      transcriptional regulators CCAAT enhancer-binding protein beta (C/EBPbeta),
      forkhead box O1 (FOXO1), and p300 to the IGFBP-1 enhancer in ESCs. Of note,
      C/EBPbeta knockdown inhibited the stimulatory effects of cAMP on the levels of
      H3K27ac, chromatin opening, and p300 recruitment at the IGFBP-1 enhancer. These
      results indicate that the region -4701 to -7501 bp upstream of IGFBP-1 functions
      as an enhancer for IGFBP-1 expression in ESCs undergoing decidualization, that
      C/EBPbeta and FOXO1 bind to the enhancer region to up-regulate IGFBP-1
      expression, and that C/EBPbeta induces H3K27ac by recruiting p300 to the IGFBP-1
      enhancer.

PMID- 29453286
TI  - Chaperone substrate provides missing link for cancer drug discovery.
AB  - Both Hsp70 and Hsp90 chaperones are overexpressed in cancer, making them relevant
      targets for the development of cancer chemotherapeutics, but a lack of
      biomolecular readouts for Hsp70 inhibition has limited the pursuit of specific
      inhibitors for this enzyme. A new study from Cesa et al. identifies two
      inhibitors of apoptosis proteins (IAPs) as specific client substrates of Hsp70.
      These results establish biomarkers that can be utilized to monitor Hsp70
      inhibition and provide a framework for future efforts to deconvolute chaperone
      networks.

PMID- 29453287
TI  - Adoption of Sacubitril/Valsartan for the Management of Patients With Heart
      Failure.
AB  - BACKGROUND: The US Food and Drug Administration approved the use of
      sacubitril/valsartan in patients with heart failure with reduced ejection
      fraction in July 2015. We aimed to assess the adoption and prescription drug
      costs of sacubitril/valsartan in its first 18 months after Food and Drug
      Administration approval. METHODS AND RESULTS: Using a large US insurance
      database, we identified privately insured and Medicare Advantage beneficiaries
      who filled a first prescription for sacubitril/valsartan between July 1, 2015,
      and December 31, 2016. We compared them to patients treated with an angiotensin
      converting enzyme inhibitor or angiotensin receptor blocker. Outcomes included
      adoption, prescription drug costs, and 180-day adherence, defined as a proportion
      of days covered >=80%. A total of 2244 patients initiated sacubitril/valsartan.
      Although the number of users increased over time, the proportion of heart failure
      with reduced ejection fraction patients taking sacubitril/valsartan remained low
      (<3%). Patients prescribed sacubitril/valsartan were younger, more often male,
      with less comorbidity than those taking an angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker. Although a majority of prescription costs
      were covered by the health plan (mean, $328.37; median, $362.44 per 30-day
      prescription), out-of-pocket costs were still high (mean, $71.16; median,
      $40.27). By comparison, median out-of-pocket costs were $2 to $3 for lisinopril,
      losartan, carvedilol, and spironolactone. Overall, 59.1% of patients were
      adherent to sacubitril/valsartan. Refill patterns suggested that nearly half of
      nonadherent patients discontinued sacubitril/valsartan within 180 days of
      starting. CONCLUSIONS: Adoption of sacubitril/valsartan after Food and Drug
      Administration approval has been slow and may be associated with the high cost.

PMID- 29453288
TI  - From Molecules to Markets: Broadening the Focus of Cardiovascular Innovation.

PMID- 29453289
TI  - Intracardiac Echinococcal Cyst Causing Biventricular Cavity Obliteration.

PMID- 29453290
TI  - Mouse and human HSPC immobilization in liquid culture by CD43- or CD44-antibody
      coating.
AB  - Keeping track of individual cell identifications is imperative to the study of
      dynamic single-cell behavior over time. Highly motile hematopoietic stem and
      progenitor cells (HSPCs) migrate quickly and do not adhere, and thus must be
      imaged very frequently to keep cell identifications. Even worse, they are also
      flushed away during medium exchange. To overcome these limitations, we tested
      antibody coating for reducing HSPC motility in vitro. Anti-CD43- and anti-CD44
      antibody coating reduced the cell motility of mouse and human HSPCs in a
      concentration-dependent manner. This enables 2-dimensional (2D) colony formation
      without cell mixing in liquid cultures, massively increases time-lapse imaging
      throughput, and also maintains cell positions during media exchange. Anti-CD43
      but not anti-CD44 coating reduces mouse HSPC proliferation with increasing
      concentrations. No relevant effects on cell survival or myeloid and megakaryocyte
      differentiation of hematopoietic stem cells and multipotent progenitors 1-5 were
      detected. Human umbilical cord hematopoietic CD34+ cell survival, proliferation,
      and differentiation were not affected by either coating. This approach both
      massively simplifies and accelerates continuous analysis of suspension cells, and
      enables the study of their behavior in dynamic rather than static culture
      conditions over time.

PMID- 29453291
TI  - LSD1 inhibition exerts its antileukemic effect by recommissioning PU.1- and
      C/EBPalpha-dependent enhancers in AML.
AB  - Epigenetic regulators are recurrently mutated and aberrantly expressed in acute
      myeloid leukemia (AML). Targeted therapies designed to inhibit these chromatin
      modifying enzymes, such as the histone demethylase lysine-specific demethylase 1
      (LSD1) and the histone methyltransferase DOT1L, have been developed as novel
      treatment modalities for these often refractory diseases. A common feature of
      many of these targeted agents is their ability to induce myeloid differentiation,
      suggesting that multiple paths toward a myeloid gene expression program can be
      engaged to relieve the differentiation blockade that is uniformly seen in AML. We
      performed a comparative assessment of chromatin dynamics during the treatment of
      mixed lineage leukemia (MLL)-AF9-driven murine leukemias and MLL-rearranged
      patient-derived xenografts using 2 distinct but effective differentiation
      inducing targeted epigenetic therapies, the LSD1 inhibitor GSK-LSD1 and the DOT1L
      inhibitor EPZ4777. Intriguingly, GSK-LSD1 treatment caused global gains in
      chromatin accessibility, whereas treatment with EPZ4777 caused global losses in
      accessibility. We captured PU.1 and C/EBPalpha motif signatures at LSD1 inhibitor
      induced dynamic sites and chromatin immunoprecipitation coupled with high
      throughput sequencing revealed co-occupancy of these myeloid transcription
      factors at these sites. Functionally, we confirmed that diminished expression of
      PU.1 or genetic deletion of C/EBPalpha in MLL-AF9 cells generates resistance of
      these leukemias to LSD1 inhibition. These findings reveal that pharmacologic
      inhibition of LSD1 represents a unique path to overcome the differentiation block
      in AML for therapeutic benefit.

PMID- 29453292
TI  - Clonal selection drives protective memory B cell responses in controlled human
      malaria infection.
AB  - Affinity maturation, the clonal selection and expansion of antigen-activated B
      cells expressing somatically mutated antibody variants that develop during T cell
      dependent germinal center reactions, is considered pivotal for efficient
      development of protective B cell memory responses to infection and vaccination.
      Repeated antigen exposure promotes affinity maturation but each time also
      recruits antigen-reactive naive B cells into the response. Here, we determined
      the relative impact of affinity maturation versus antigen-mediated clonal
      selection of naive B cells to mount potent B cell memory responses in humans
      after repeated exposure to a complex pathogen, the malaria parasite Plasmodium
      falciparum (Pf). Using single-cell immunoglobulin (Ig) gene sequencing and
      production of recombinant monoclonal antibodies, we analyzed the origin,
      development, and quality of memory B cell responses to Pf circumsporozoite
      protein (PfCSP), the major sporozoite surface protein. We show that after
      repeated immunization of Pf-naive volunteers with infectious Pf sporozoites
      (PfSPZ Challenge) under chloroquine prophylaxis (PfSPZ-CVac), the clonal
      selection of potent germline and memory B cell precursors against the central
      PfCSP NANP repeat outpaces affinity maturation because the majority of Ig gene
      mutations are affinity-neutral. Mathematical modeling explains how the efficiency
      of affinity maturation decreases strongly with antigen complexity. Thus, in the
      absence of long-term exposure, the frequency of antigen-reactive precursors and
      likelihood of their activation rather than affinity maturation will determine the
      quality of anti-PfCSP memory B cell responses. These findings have wide
      implications for the design of vaccination strategies to induce potent B cell
      memory responses against PfCSP and presumably other structurally complex
      antigens.

PMID- 29453294
TI  - Public preferences for interventions to prevent emerging infectious disease
      threats: a discrete choice experiment.
AB  - OBJECTIVE: When faced with an emergent epidemic with high mortality and morbidity
      potential, policy makers must decide what public health interventions to deploy
      at different stages of the outbreak. However, almost nothing is known about how
      the public view these interventions or how they trade off risks (of disease) with
      inconvenience (of interventions). In this paper, we aim to understand public
      perceptions on pandemic interventions, as well as to identify if there are any
      distinct respondent preference classes. DESIGN: A discrete choice experiment.
      SETTING: This study was fielded in Singapore between November 2012 and February
      2013. PARTICIPANTS: A random sample of 500 Singapore residents aged 21 and over,
      including 271 women and 229 men, was analysed. OUTCOME MEASURES: Demographic
      information was collected from each participant. Participants were also shown a
      series of pairs of alternatives, each combining interventions and morbidity,
      mortality and cost outcomes and declared a preference for one combination. A
      random utility model was developed to determine the individual's preference for
      interventions and a hierarchical cluster analysis was performed to identify
      distinct respondent preference classes. RESULTS: On average, participants
      preferred more intense interventions, and preferred scenarios with fewer deaths
      and lower tax. The number of infections did not significantly influence
      respondents' responses. We identified two broad classes of respondents: those who
      were mortality averse and those who were expenditure averse. Education was found
      to be a predictor of group membership. CONCLUSION: Overall, there was
      considerable support for government interventions to prevent or mitigate
      outbreaks of emerging infectious diseases, including those that greatly
      restricted individual liberties, as long as the restrictions showed a reasonable
      chance of reducing the adverse health effects of the outbreak.

PMID- 29453293
TI  - Protein phosphorylation maintains the normal function of cloned human Cav2.3
      channels.
AB  - R-type currents mediated by native and recombinant Cav2.3 voltage-gated Ca2+
      channels (VGCCs) exhibit facilitation (run-up) and subsequent decline (run-down)
      in whole-cell patch-clamp recordings. A better understanding of the two processes
      could provide insight into constitutive modulation of the channels in intact
      cells, but low expression levels and the need for pharmacological isolation have
      prevented investigations in native systems. Here, to circumvent these
      limitations, we use conventional and perforated-patch-clamp recordings in a
      recombinant expression system, which allows us to study the effects of cell
      dialysis in a reproducible manner. We show that the decline of currents carried
      by human Cav2.3+beta3 channel subunits during run-down is related to adenosine
      triphosphate (ATP) depletion, which reduces the number of functional channels and
      leads to a progressive shift of voltage-dependent gating to more negative
      potentials. Both effects can be counteracted by hydrolysable ATP, whose
      protective action is almost completely prevented by inhibition of
      serine/threonine but not tyrosine or lipid kinases. Protein kinase inhibition
      also mimics the effects of run-down in intact cells, reduces the peak current
      density, and hyperpolarizes the voltage dependence of gating. Together, our
      findings indicate that ATP promotes phosphorylation of either the channel or an
      associated protein, whereas dephosphorylation during cell dialysis results in run
      down. These data also distinguish the effects of ATP on Cav2.3 channels from
      those on other VGCCs because neither direct nucleotide binding nor PIP2 synthesis
      is required for protection from run-down. We conclude that protein
      phosphorylation is required for Cav2.3 channel function and could directly
      influence the normal features of current carried by these channels. Curiously,
      some of our findings also point to a role for leupeptin-sensitive proteases in
      run-up and possibly ATP protection from run-down. As such, the present study
      provides a reliable baseline for further studies on Cav2.3 channel regulation by
      protein kinases, phosphatases, and possibly proteases.

PMID- 29453295
TI  - Socioeconomic, religious, spiritual and health factors associated with symptoms
      of common mental disorders: a cross-sectional secondary analysis of data from
      Bhutan's Gross National Happiness Study, 2015.
AB  - OBJECTIVE: Common mental disorders (CMDs) are a major cause of the global burden
      of disease. Bhutan was the first country in the world to focus on happiness as a
      state policy; however, little is known about the prevalence and risk factors of
      CMDs in this setting. We aim to identify socioeconomic, religious, spiritual and
      health factors associated with symptoms of CMDs. DESIGN AND SETTING: We used data
      from Bhutan's 2015 Gross National Happiness (GNH) Survey, a multistage, cross
      sectional nationwide household survey. Data were analysed using a hierarchical
      analytical framework and generalised estimating equations. PARTICIPANTS: The GNH
      Survey included 7041 male and female respondents aged 15 years and above.
      MEASURES: The 12-item General Health Questionnaire was used to measure symptoms
      of CMDs. We estimated the prevalence of CMDs using a threshold score of >=12.
      RESULTS: The prevalence of CMDs was 29.3% (95% CI 26.8% to 31.8%). Factors
      associated with symptoms of CMDs were: older age (65+) (beta=1.29, 95% CI 0.57 to
      2.00), being female (beta=0.70, 95% CI 0.45 to 0.95), being divorced or widowed
      (beta=1.55, 95% CI 1.08 to 2.02), illiteracy (beta=0.48, 95% CI 0.21 to 0.74),
      low income (beta=0.37, 95% CI 0.15 to 0.59), being moderately spiritual
      (beta=0.61, 95% CI 0.34 to 0.88) or somewhat or not spiritual (beta=0.76, 95% CI
      0.28 to 1.23), occasionally considering karma in daily life (beta=0.53, 95% CI
      0.29 to 0.77) or never considering karma (beta=0.80, 95% CI 0.26 to 1.34), having
      poor self-reported health (beta=2.59, 95% CI 2.13 to 3.06) and having a
      disability (beta=1.01, 95% CI 0.63 to 1.40). CONCLUSIONS: CMDs affect a
      substantial proportion of the Bhutanese population. Our findings confirm the
      importance of established socioeconomic risk factors for CMDs, and suggest a
      potential link between spiritualism and mental health in this setting.

PMID- 29453296
TI  - Understanding the characteristics of recurrent visits to the emergency department
      by paediatric patients: a retrospective observational study conducted at three
      tertiary hospitals in Korea.
AB  - OBJECTIVES: The number of paediatric patients visiting the emergency department
      (ED) continues to rise. In South Korea, approximately 25% of the patients who
      visit the ED are paediatric patients. In the USA, about 20% of the paediatric
      population were found to have visited the ED in the past year. A recent study
      demonstrated that 4.5%-8% of patients account for 25% of all ED visits.
      Therefore, the aim of this study was to identify the characteristics of recurrent
      visits. METHODS: Design: retrospective observational study. SETTING: this study
      examined and analysed medical record data involving three tertiary EDs.
      PARTICIPANTS: a total of 46 237 ED visits by patients <16 years during 1-year
      period. MAIN OUTCOME MEASURES: data collected included the number of recurrent ED
      patients, frequency of recurrent visits, age, sex, insurance status, period until
      recurrent visit (days), main diagnosis and ED discharge results. RESULTS:
      Excluding patients with multiple visits, the total number of paediatric patients
      who fit the study criteria was 33 765. Among these patients, 23 384 (69.2%) had
      no recurrent ED visits in the subsequent year after their first visit. A total of
      15 849 (46.8%) patients were toddlers (between age 1 and 4 years). In the patient
      group without a recurrent visit, fever was the most common diagnosis.
      CONCLUSIONS: Our study reviewed medical records to inspect the characteristics of
      patients who return to care. Higher recurrent visit frequency was associated with
      using the 119 rescue centre service, having a medical condition, with younger age
      and a higher rate of hospitalisation. Analysis of the factors associated with
      frequent ED visits will help to improve care for paediatric patients who visit
      the ED.

PMID- 29453297
TI  - What factors mediate the inter-relationship between frailty and pain in
      cognitively and functionally sound older adults? A prospective longitudinal
      ageing cohort study in Taiwan.
AB  - OBJECTIVES: The main aim was to investigate the complex inter-relationship
      between frailty and pain, and the mediating roles of cognitive function,
      morbidity and mood in this nexus. DESIGN: A cross-sectional analysis. SETTING: A
      prospective community-dwelling population-based cohort. PARTICIPANTS: 1682 adults
      age >=50 years without evident cognitive or functional impairment, or history of
      cancer. PRIMARY AND SECONDARY OUTCOME MEASURES: The mediating effect of
      depression, cognitive function and comorbidity on the nexus between pain and
      frailty among older and middle-aged adults. RESULTS: The pain score among older
      subjects (>=65 years), increased with the degree of frailty (robust=0.96+/-0.82;
      pre-frail=1.13+/-0.86; frail=1.63+/-1.02; P<0.001); multivariate analysis gave
      the same result, while moderate pain was associated with frailty in older
      subjects (OR=3.00, 95% CI 1.30 to 6.60). Conversely, pain and frailty among
      middle-aged subjects (aged 50-64 years) did not appear to be significantly
      related; in mediation analysis, pain exerted an indirect effect on frailty via
      depression (indirect effect=0.03, 95% CI 0.01 to 0.07), while neither cognitive
      function nor comorbidity had any significant effect in mediating the relationship
      between pain and frailty. CONCLUSION: In cognitively and functionally sound
      community-dwelling adults aged >=50 years, moderate pain was related to frailty
      in those older than 65 years, but not younger ones. Besides the direct influence
      of pain on frailty, depression partially mediated the pain-frailty nexus. The
      mechanism by which depression influences pain and frailty requires further
      investigation.

PMID- 29453298
TI  - Urban green spaces and cancer: a protocol for a scoping review.
AB  - INTRODUCTION: Green space in the built environment is an important topic on the
      health agenda today. Studies have shown that access to green spaces is associated
      with better mental and physical health, yet green spaces can also be detrimental
      to health if they are not managed appropriately. Despite the increasing interest
      in urban green spaces, little research has so far been conducted into the links
      between green spaces and cancer. OBJECTIVE: The purpose of this scoping review is
      therefore to map the literature available on the types of relationship between
      urban green spaces and cancer. METHOD AND ANALYSIS: We followed the Preferred
      Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guideline
      to report the protocol. To conduct this scoping review, we will use a structured
      search strategy based on controlled vocabulary and relevant key terms related to
      green space, urban space and cancer. We will search MEDLINE (PubMed), GreenFILE
      (EBSCOhost), Cumulative Index to Nursing and Allied Health Literature (EBSCOhost)
      and ScienceDirect as electronic database as well as hand-search publications for
      grey literature. This review will therefore provide evidence on this current
      topic, one which could have practical implications for policy-makers involved in
      choices which are more conducive to healthy living. ETHICS AND DISSEMINATION: No
      primary data will be collected since all data that will be presented in this
      review are based on published articles and publicly available documents, and
      therefore ethics committee approval is not a requirement. The findings of this
      review will be presented at workshops and conferences, and will be submitted for
      publication in a peer-reviewed journal.

PMID- 29453299
TI  - Pulmonary sarcoidosis with and without extrapulmonary involvement: a cross
      sectional and observational study in China.
AB  - OBJECTIVES: Sarcoidosis is a multisystem disease characterised by the formation
      of granulomas within various organs, mainly the lungs. Several studies from
      different countries have been undertaken to investigate sarcoidosis with
      extrapulmonary involvement except from China. The objective of this study is to
      investigate a comparative clinical analysis in patients with pulmonary
      sarcoidosis with and without extrapulmonary involvement from China. METHODS: Data
      from inpatients diagnosed with sarcoidosis at Shanghai Pulmonary Hospital
      (Shanghai, China) between January 2009 and December 2014 were retrospectively
      collected and analysed. Six hundred and thirty-six patients with biopsy-proven
      sarcoidosis were included in the study, including 378 isolated pulmonary
      sarcoidosis and 258 pulmonary sarcoidosis plus extrapulmonary involvement.
      RESULTS: Two hundred and fifty-eight (40.6%) patients with pulmonary sarcoidosis
      had extrapulmonary involvement. Extrapulmonary localisations were detected mostly
      in extrathoracic lymph nodes (n=147) and skin (n=86). Statistically significant
      differences were demonstrated between patients with pulmonary sarcoidosis plus
      extrapulmonary involvement and patients with isolated pulmonary sarcoidosis for
      fatigue (16.6%vs8.3%, P<0.05), serum ACE (SACE) levels (79.0+/-46.9 IU/L vs
      69.7+/-38.7 IU/L, P<0.05), and high-resolution CT (HRCT) findings (53.8%vs46.2%,
      P<0.05). CONCLUSIONS: Extrapulmonary involvement is common in patients with
      pulmonary sarcoidosis, with the most common sites being extrathoracic lymph nodes
      and skin. Patients with sarcoidosis with extrapulmonary involvement are more
      symptomatic (fatigue), have higher SACE levels and more deteriorating HRCT
      findings, to which clinicians should pay attention.

PMID- 29453300
TI  - School-based lifestyle education involving parents for reducing subjective
      psychosomatic symptoms in Japanese adolescents: study protocol for a cluster
      randomised controlled trial.
AB  - INTRODUCTION: Severe subjective psychosomatic symptoms (SPS) in adolescents are a
      major public health concern, and lifestyle modification interventions for
      reducing SPS are important topics. Recently, we developed a school-based
      lifestyle education involving parents for reducing SPS of adolescents (SPRAT), an
      improved version of the programme from our previous study Programme for
      adolescent of lifestyle education in Kumamoto (PADOK). This study aimed to
      evaluate the effectiveness of SPRAT in reducing SPS among adolescents. METHODS
      AND ANALYSIS: This is a 6-month, cluster randomised clinical trial with two
      intervention arms (SPRAT vs usual school education). The study population will be
      composed of middle school students (aged 12-14 years) with their
      parents/guardians in Japan. SPRAT is expected to be a more powerful programme
      than PADOK as it reinforces the role of parent participation. The primary
      endpoint will be the change from baseline SPS scores to those obtained after 6
      months. Between-group differences will be analysed following the intention-to
      treat principle. Crude and multivariate adjusted effects will be examined using a
      general linear mixed-effects model for continuous variables and a logistic
      regression model for dichotomous variables. The sample size required was
      determined based on the information needed to detect a difference in the primary
      outcome with a significance level of 5% and power of 80% under the assumptions of
      40 students per cluster (assuming the same sample size for each cluster), an
      effect size of 0.3 and an intraclass correlation coefficient of 0.02. In total,
      participation by 28 schools (14 schools in each arm) (students: n=1120) will be
      needed. ETHICS AND DISSEMINATION: This study was approved by the Medical Ethical
      Committee of Minami Kyushu University in 2017 (number 137). The findings will be
      disseminated widely through peer-reviewed publications and conference
      presentations. TRIAL REGISTRATION NUMBER: UMIN000026715; Pre-results.

PMID- 29453302
TI  - Characteristics and publication fate of unregistered and retrospectively
      registered clinical trials submitted to The BMJ over 4 years.
AB  - OBJECTIVES: We sought to evaluate the characteristics and publication fate of
      improperly registered clinical trials submitted to a medical journal (The BMJ)
      over a 4-year period to identify common types of registration issues and their
      relation to publication outcomes. DESIGN: Research articles submitted to The BMJ
      and identified as unregistered or retrospectively registered by editors were
      included if they reported outcomes of a clinical trial. Relevant data regarding
      the trials were then extracted from each paper. Trials were categorised as
      prospectively registered, registered in an unapproved registry, unregistered or
      other, and explanations for registration deficiencies were grouped into six
      categories. We searched PubMed and Google to determine whether, where and when
      improperly registered studies were subsequently published and whether
      registration issues were disclosed. RESULTS: 123 research papers reporting
      apparently unregistered or retrospectively registered clinical trials were
      identified. 110 studies (89.4%) were retrospectively registered, nine (7.3%) were
      unregistered, three (2.4%) had been registered in an unapproved registry and one
      study originally lacking registration details was later discovered to have been
      prospectively registered. 82 studies (66.6%) were funded entirely or in part by
      government sources, and only seven studies (5.7%) received funding from industry.
      Of those papers submitted to The BMJ through the end of 2015, 67 of the 70 papers
      rejected for registration problems (95.7%) were subsequently published in another
      journal. The registration problem was disclosed in only 2 (2.9%). CONCLUSIONS:
      Improper registration remains a problem, particularly for clinical trials that
      are government or foundation-funded. Nonetheless, improperly registered trials
      are almost always published, suggesting that medical journal editors may not
      actively enforce registration requirements.

PMID- 29453303
TI  - Identifying positively deviant elderly medical wards using routinely collected
      NHS Safety Thermometer data: an observational study.
AB  - OBJECTIVE: The positive deviance approach seeks to identify and learn from
      exceptional performers. Although a framework exists to apply positive deviance
      within healthcare organisations, there is limited guidance to support its
      implementation. The approach has also rarely explored exceptional performance on
      broad outcomes, been implemented at ward level, or applied within the UK. This
      study develops and critically appraises a pragmatic method for identifying
      positively deviant wards using a routinely collected, broad measure of patient
      safety. DESIGN: A two-phased observational study was conducted. During phase 1,
      cross-sectional and temporal analyses of Safety Thermometer data were conducted
      to identify a discrete group of positively deviant wards that consistently
      demonstrated exceptional levels of safety. A group of matched comparison wards
      with above average performances were also identified. During phase 2,
      multidisciplinary staff and patients on the positively deviant and comparison
      wards completed surveys to explore whether their perceptions of safety supported
      the identification of positively deviant wards. SETTING: 34 elderly medical wards
      within a northern region of England, UK. PARTICIPANTS: Multidisciplinary staff
      (n=161) and patients (n=188) clustered within nine positively deviant and
      comparison wards. RESULTS: Phase 1: A combination of analyses identified five
      positively deviant wards that performed best in the region, outperformed their
      organisation and performed consistently well over 12 months. Five above average
      matched comparator wards were also identified. Phase 2: Staff and patient
      perceptions of safety generally supported the identification of positively
      deviant wards using Safety Thermometer data, although patient perceptions of
      safety were less concordant with the routinely collected data. CONCLUSIONS: This
      study tentatively supports a pragmatic method of using routinely collected data
      to identify positively deviant elderly medical wards; however, it also highlights
      the various challenges that are faced when conducting the first stage of the
      positive deviance approach. TRIAL REGISTRATION NUMBER: UK Clinical Research
      Network Portfolio (reference-18050).

PMID- 29453301
TI  - Role of the family doctor in the management of adults with obesity: a scoping
      review.
AB  - OBJECTIVES: Obesity management is an important issue for the international
      primary care community. This scoping review examines the literature describing
      the role of the family doctor in managing adults with obesity. The methods were
      prospectively published and followed Joanna Briggs Institute methodology.
      SETTING: Primary care. Adult patients. INCLUDED PAPERS: Peer-reviewed and grey
      literature with the keywords obesity, primary care and family doctors. All
      literature published up to September 2015. 3294 non-duplicate papers were
      identified and 225 articles included after full-text review. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Data were extracted on the family doctors'
      involvement in different aspects of management, and whether whole person and
      person-centred care were explicitly mentioned. RESULTS: 110 papers described
      interventions in primary care and family doctors were always involved in
      diagnosing obesity and often in recruitment of participants. A clear description
      of the provider involved in an intervention was often lacking. It was difficult
      to determine if interventions took account of whole person and person
      centredness. Most opinion papers and clinical overviews described an extensive
      role for the family doctor in management; in contrast, research on current
      practices depicted obesity as undermanaged by family doctors. International
      guidelines varied in their description of the role of the family doctor with a
      more extensive role suggested by guidelines from family medicine organisations.
      CONCLUSIONS: There is a disconnect between how family doctors are involved in
      primary care interventions, the message in clinical overviews and opinion papers,
      and observed current practice of family doctors. The role of family doctors in
      international guidelines for obesity may reflect the strength of primary care in
      the originating health system. Reporting of primary care interventions could be
      improved by enhanced descriptions of the providers involved and explanation of
      how the pillars of primary care are used in intervention development.

PMID- 29453305
TI  - Frequency and Outcomes of Reduced Dose Non-Vitamin K Antagonist Anticoagulants:
      Results From ORBIT-AF II (The Outcomes Registry for Better Informed Treatment of
      Atrial Fibrillation II).
AB  - BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are indicated
      for stroke prevention in atrial fibrillation (AF) but require lower doses in
      certain patients. We sought to describe the frequency, appropriateness (according
      to Food and Drug Administration labeling), and outcomes of patients prescribed
      reduced doses of NOACs in community practice. METHODS AND RESULTS: We analyzed
      data from the ORBIT-AF II (The Outcomes Registry for Better Informed Treatment of
      Atrial Fibrillation II) registry, a prospective, national, observational registry
      of AF patients. Among 7925 AF patients receiving NOACs, we assessed patterns of
      use of reduced NOAC doses and associated cardiovascular and bleeding outcomes at
      median follow-up of 1 year. Overall, 6636 patients (84%) received a NOAC at
      standard dose, which was consistent with US Food and Drug Administration labeling
      in 6376 (96%). Reduced NOAC dose was prescribed to 1289 (16% overall), which was
      consistent with Food and Drug Administration labeling in only 555 patients (43%).
      Compared with those whose NOAC dose was appropriately reduced, patients receiving
      inappropriate dose reductions were younger (median age 79 versus 84, P<0.0001)
      and had lower ORBIT bleeding risk scores (26% >=4 versus 45%, P<0.0001). Compared
      with those appropriately receiving standard dosing, patients receiving
      inappropriately reduced-dose NOACs had higher unadjusted rates of thromboembolic
      events (2.11 versus 1.35 events per 100 patient years, hazard ratio 1.56, 95%
      confidence interval 0.92-2.67) and death (6.77 versus 2.60, hazard ratio 2.61,
      95% confidence interval 1.86-3.67). After adjustment, outcomes were not
      significantly different but tended to favor patients dosed appropriately.
      CONCLUSIONS: The majority of dose reductions of NOACs in AF are inconsistent with
      US Food and Drug Administration recommendations. There appear to be opportunities
      to improve current NOAC dosing in community practice. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01701817.

PMID- 29453304
TI  - Protocol investigating the clinical utility of an objective measure of attention,
      impulsivity and activity (QbTest) for optimising medication management in
      children and young people with ADHD 'QbTest Utility for Optimising Treatment in
      ADHD' (QUOTA): a feasibility randomised controlled trial.
AB  - INTRODUCTION: Attention-deficit hyperactivity disorder (ADHD) is characterised by
      symptoms of inattention, hyperactivity and impulsivity. To improve outcomes, the
      National Institute for Health and Care Excellence ADHD guidelines recommend
      regular monitoring of symptoms when children commence medication. However,
      research suggests that routine monitoring rarely happens, and clinicians often
      rely on subjective information such as reports from parents and teachers to
      ascertain improvement. These sources can be unreliable and difficult to obtain.
      The addition of an objective test of attention and activity (QbTest) may improve
      the objectivity, reliability and speed of clinical decision-making and so reduce
      the time to identify the optimal medication dose. This study aims to assess the
      feasibility and acceptability of a QbTest medication management protocol
      delivered in routine healthcare services for children with ADHD. METHOD AND
      ANALYSIS: This multisite feasibility randomised controlled trial (RCT) will
      recruit 60 young people (aged 6-17 years old), diagnosed with ADHD, and starting
      stimulant medication who are seen by Child and Adolescent Mental Health Services
      or Community Paediatric services. Participants will be randomised into one of two
      arms. In the experimental arm (QbTest protocol), the participant will complete a
      QbTest at baseline (prior to medication initiation), and two follow-up QbTests on
      medication (2-4 weeks and 8-10 weeks later). In the control arm, participants
      will receive treatment as usual, with at least two follow-up consultations.
      Measures of parent-, teacher- and clinician-rated symptoms and global functioning
      will be completed at each time point. Health economic measures will be completed.
      Clinicians will record treatment decision-making. Acceptability and feasibility
      of the protocol will be assessed alongside outcome measure completion rates.
      Qualitative interviews will be conducted. ETHICS AND DISSEMINATION: The findings
      will be used to inform the development of a fully powered RCT. The results will
      be submitted for publication in peer-reviewed journals. The study has ethical
      approval. TRIAL REGISTRATION NUMBER: NCT03368573; Pre-results.

PMID- 29453306
TI  - Acute Pressor Response to Psychosocial Stress Is Dependent on Endothelium-Derived
      Endothelin-1.
AB  - BACKGROUND: Acute psychosocial stress provokes increases in circulating
      endothelin-1 (ET-1) levels in humans and animal models. However, key questions
      about the physiological function and cellular source of stress-induced ET-1
      remain unanswered. We hypothesized that endothelium-derived ET-1 contributes to
      the acute pressor response to stress via activation of the endothelin A receptor.
      METHODS AND RESULTS: Adult male vascular endothelium-specific ET-1 knockout mice
      and control mice that were homozygous for the floxed allele were exposed to acute
      psychosocial stress in the form of cage switch stress (CSS), with blood pressure
      measured by telemetry. An acute pressor response was elicited by CSS in both
      genotypes; however, this response was significantly blunted in vascular
      endothelium-specific ET-1 knockout mice compared with control mice that were
      homozygous for the floxed allele. In mice pretreated for 3 days with the
      endothelin A antagonist, ABT-627, or the dual endothelin A/B receptor antagonist,
      A-182086, the pressor response to CSS was similar between genotypes. CSS
      significantly increased plasma ET-1 levels in control mice that were homozygous
      for the floxed allele. CSS failed to elicit an increase in plasma ET-1 in
      vascular endothelium-specific ET-1 knockout mice. Telemetry frequency domain
      analyses suggested similar autonomic responses to stress between genotypes, and
      isolated resistance arteries demonstrated similar sensitivity to alpha1
      adrenergic receptor-mediated vasoconstriction. CONCLUSIONS: These findings
      specify that acute stress-induced activation of endothelium-derived ET-1 and
      subsequent endothelin A receptor activation is a novel mediator of the blood
      pressure response to acute psychosocial stress.

PMID- 29453307
TI  - Delirium in the Cardiac Intensive Care Unit.

PMID- 29453308
TI  - Sex-Specific Mechanisms of Resistance Vessel Endothelial Dysfunction Induced by
      Cardiometabolic Risk Factors.
AB  - BACKGROUND: The incidence of obesity is rising, particularly among women.
      Microvascular dysfunction is more common with female sex, obesity, and
      hyperlipidemia and predicts adverse cardiovascular outcomes, but the molecular
      mechanisms are unclear. Because obesity is associated with mineralocorticoid
      receptor (MR) activation, we tested the hypothesis that MR in endothelial cells
      contribute to sex differences in resistance vessel dysfunction in response to
      cardiometabolic risk factors. METHODS AND RESULTS: Male and female endothelial
      cell-specific MR knockout mice and MR-intact littermates were randomized to high
      fat-diet-induced obesity or obesity with hyperlipidemia induced by adeno
      associated virus-based vector targeting transfer of the mutant stable form (DY
      mutation) of the human PCSK9 (proprotein convertase subtilisin/kexin type 9) gene
      and compared with control diet. Female but not male mice were sensitive to
      obesity-induced endothelial dysfunction, whereas endothelial function was
      impaired in obese hyperlipidemic males and females. In males, obesity or
      hyperlipidemia decreased the nitric oxide component of vasodilation without
      altering superoxide production or endothelial nitric oxide synthase expression or
      phosphorylation. Decreased nitric oxide content in obese males was overcome by
      enhanced endothelium-derived hyperpolarization-mediated relaxation along with
      increased SK3 expression. Conversely, in females, endothelium-derived
      hyperpolarization was significantly impaired by obesity with lower IK1 expression
      and by hyperlipidemia with lower IK1 and SK3 expression, loss of H2O2-mediated
      vasodilation, and increased superoxide production. Endothelial cell-MR deletion
      prevented endothelial dysfunction induced by risk factors only in females. Rather
      than restoring endothelium-derived hyperpolarization in females, endothelial cell
      MR deletion enhanced nitric oxide and prevented hyperlipidemia-induced oxidative
      stress. CONCLUSIONS: These data reveal distinct mechanisms driving resistance
      vessel dysfunction in males versus females and suggest that personalized
      treatments are needed to prevent the progression of vascular disease in the
      setting of obesity, depending on both the sex and the metabolic profile of each
      patient.

PMID- 29453310
TI  - Do migrating cells need a nucleus?
AB  - How the nucleus affects cell polarity and migration is unclear. In this issue,
      Graham et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201706097) show
      that enucleated cells polarize and migrate in two but not three dimensions and
      propose that the nucleus is a necessary component of the molecular clutch
      regulating normal mechanical responses.

PMID- 29453309
TI  - Sutureless Perceval Aortic Valve Versus Conventional Stented Bioprostheses: Meta
      Analysis of Postoperative and Midterm Results in Isolated Aortic Valve
      Replacement.
AB  - BACKGROUND: Aortic stenosis is the most common valvular disease and has a dismal
      prognosis without surgical treatment. The aim of this meta-analysis was to
      quantitatively assess the comparative effectiveness of the Perceval (LivaNova)
      valve versus conventional aortic bioprostheses. METHODS AND RESULTS: A total of 6
      comparative studies were identified, including 639 and 760 patients who
      underwent, respectively, aortic valve replacement with the Perceval sutureless
      valve (P group) and with a conventional bioprosthesis (C group). Aortic cross
      clamping and cardiopulmonary bypass duration were significantly lower in the P
      group. No difference in postoperative mortality was shown for the P and C groups
      (2.8% versus 2.7%, respectively; odds ratio [OR]: 0.99 [95% confidence interval
      (CI), 0.52-1.88]; P=0.98). Incidence of postoperative renal failure was lower in
      the P group compared with the C group (2.7% versus 5.5%; OR: 0.45 [95% CI, 0.25
      0.80]; P=0.007). Incidence of stroke (2.3% versus 1.7%; OR: 1.34 [95% CI, 0.56
      3.21]; P=0.51) and paravalvular leak (3.1% versus 1.6%; OR: 2.52 [95% CI, 0.60
      1.06]; P=0.21) was similar, whereas P group patients received fewer blood
      transfusions than C group patients (1.16+/-1.2 versus 2.13+/-2.2; mean
      difference: 0.99 [95% CI, -1.22 to -0.75]; P=0.001). The incidence of pacemaker
      implantation was higher in the P than the C group (7.9% versus 3.1%; OR: 2.45
      [95% CI, 1.44-4.17]; P=0.001), whereas hemodynamic Perceval performance was
      better (transvalvular gradient 23.42+/-1.73 versus 22.8+/-1.86; mean difference:
      0.90 [95% CI, 0.62-1.18]; P=0.001), even during follow-up (10.98+/-5.7 versus
      13.06+/-6.2; mean difference: -2.08 [95% CI, -3.96 to -0.21]; P=0.030). We found
      no difference in 1-year mortality. CONCLUSIONS: The Perceval bioprosthesis
      improves the postoperative course compared with conventional bioprostheses and is
      an option for high-risk patients.

PMID- 29453311
TI  - Visualization of ligand-induced transmembrane signaling in the full-length human
      insulin receptor.
AB  - Insulin receptor (IR) signaling plays a critical role in the regulation of
      metabolism and growth in multicellular organisms. IRs are unique among receptor
      tyrosine kinases in that they exist exclusively as covalent (alphabeta)2
      homodimers at the cell surface. Transmembrane signaling by the IR can therefore
      not be based on ligand-induced dimerization as such but must involve structural
      changes within the existing receptor dimer. In this study, using glycosylated
      full-length human IR reconstituted into lipid nanodiscs, we show by single
      particle electron microscopy that insulin binding to the dimeric receptor
      converts its ectodomain from an inverted U-shaped conformation to a T-shaped
      conformation. This structural rearrangement of the ectodomain propagates to the
      transmembrane domains, which are well separated in the inactive conformation but
      come close together upon insulin binding, facilitating autophosphorylation of the
      cytoplasmic kinase domains.

PMID- 29453312
TI  - Inhibition of Ras activity coordinates cell fusion with cell-cell contact during
      yeast mating.
AB  - In the fission yeast Schizosaccharomyces pombe, pheromone signaling engages a
      signaling pathway composed of a G protein-coupled receptor, Ras, and a mitogen
      activated protein kinase (MAPK) cascade that triggers sexual differentiation and
      gamete fusion. Cell-cell fusion requires local cell wall digestion, which relies
      on an initially dynamic actin fusion focus that becomes stabilized upon local
      enrichment of the signaling cascade on the structure. We constructed a live
      reporter of active Ras1 (Ras1-guanosine triphosphate [GTP]) that shows Ras
      activity at polarity sites peaking on the fusion structure before fusion.
      Remarkably, constitutive Ras1 activation promoted fusion focus stabilization and
      fusion attempts irrespective of cell pairing, leading to cell lysis. Ras1
      activity was restricted by the guanosine triphosphatase-activating protein Gap1,
      which was itself recruited to sites of Ras1-GTP and was essential to block
      untimely fusion attempts. We propose that negative feedback control of Ras
      activity restrains the MAPK signal and couples fusion with cell-cell engagement.

PMID- 29453313
TI  - Multigene Profiling of CTCs in mCRPC Identifies a Clinically Relevant Prognostic
      Signature.
AB  - The trend toward precision-based therapeutic approaches dictated by molecular
      alterations offers substantial promise for men with metastatic castration
      resistant prostate cancer (mCRPC). However, current approaches for molecular
      characterization are primarily tissue based, necessitating serial biopsies to
      understand changes over time and are limited by the challenges inherent to
      extracting genomic material from predominantly bone metastases. Therefore, a
      circulating tumor cell (CTC)-based assay was developed to determine gene
      expression across a panel of clinically relevant and potentially actionable
      prostate cancer-related genes. CTCs were isolated from the whole blood of mCRPC
      patients (n = 41) and multiplex qPCR was performed to evaluate expression of
      prostate cancer-related target genes (n = 78). A large fraction of patients
      (27/41, 66%) had detectable CTCs. Increased androgen receptor (AR) expression
      (70% of samples) and evidence of Wnt signaling (67% of samples) were observed.
      The TMPRSS2:ERG fusion was expressed in 41% of samples, and the aggressive
      prostate cancer-associated long noncoding RNA SChLAP1 was upregulated in 70%.
      WNT5a [HR 3.62, 95% confidence interval (CI), 1.63-8.05, P = 0.002], AURKA (HR
      5.56, 95% CI, 1.79-17.20, P = 0.003), and BMP7 (HR 3.86, 95% CI, 1.60-9.32, P =
      0.003) were independently predictive of overall survival (FDR < 10%) after
      adjusting for a panel of previously established prognostic variables in mCRPC
      (Halabi nomogram). A model including Halabi, WNT5a, and AURKA expression, termed
      the miCTC score, outperformed the Halabi nomogram alone (AUC = 0.89 vs. AUC =
      0.70). Understanding the molecular landscape of CTCs has utility in predicting
      clinical outcomes in patients with aggressive prostate cancer and provides an
      additional tool in the arsenal of precision-based therapeutic approaches in
      oncology.Implications: Analysis of CTC gene expression reveals a clinically
      prognostic "liquid biopsy" signature in patients with metastatic castrate
      resistance prostate cancer. Mol Cancer Res; 16(4); 643-54. (c)2018 AACR.

PMID- 29453314
TI  - AR Expression in Breast Cancer CTCs Associates with Bone Metastases.
AB  - Molecular drivers underlying bone metastases in human cancer are not well
      understood, in part due to constraints in bone tissue sampling. Here, RNA
      sequencing was performed of circulating tumor cells (CTC) isolated from blood
      samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing
      cases with progression in bone versus visceral organs. Among the activated
      cellular pathways in CTCs from bone-predominant breast cancer is androgen
      receptor (AR) signaling. AR gene expression is evident, as is its constitutively
      active splice variant AR-v7. AR expression within CTCs is correlated with the
      duration of treatment with aromatase inhibitors, suggesting that it contributes
      to acquired resistance to endocrine therapy. In an established breast cancer
      xenograft model, a bone-tropic derivative displays increased AR expression, whose
      genetic or pharmacologic suppression reduces metastases to bone but not to lungs.
      Together, these observations identify AR signaling in CTCs from women with bone
      predominant ER+ breast cancer, and provide a rationale for testing androgen
      inhibitors in this subset of patients.Implications: This study highlights a role
      for the AR in breast cancer bone metastasis, and suggests that therapeutic
      targeting of the AR may benefit patients with metastatic breast cancer. Mol
      Cancer Res; 16(4); 720-7. (c)2018 AACR.

PMID- 29453315
TI  - Autophagic Flux Is Regulated by Interaction Between the C-terminal Domain of
      PATCHED1 and ATG101.
AB  - The Hedgehog (Hh) receptor Patched1 (PTCH1) is a well-known tumor suppressor that
      in its active form represses Smoothened (SMO) activity, inhibits proliferation,
      and induces apoptosis. The cytoplasmic C-terminal domain (CTD) regulates PTCH1
      turnover and nucleates a proapoptotic complex. In this study, it was
      mechanistically determined that Autophagy-related 101 (ATG101), essential for
      mammalian autophagy, physically interacts with the CTD of PTCH1 and connects it
      to the ULK complex, which stimulates the autophagy machinery in response to
      changes in nutrient availability. This interaction results in a blockade of basal
      autophagic flux and accumulation of autophagosomes with undegraded cargo.
      Remarkably, this function of PTCH1 is independent of its repressive activity on
      SMO, as shown in SMO-deficient cells or in the presence of a SMO inhibitor, but
      is opposed by Sonic Hedgehog (SHH). These findings reveal a novel noncanonical
      function of PTCH1 that limits autophagy, mediated by ATG101, which could have
      therapeutic implications in Hh-dependent cancers.Implications: Loss-of-function
      of the tumor suppressor Patched1 might promote cancer cell fitness by increasing
      autophagic flux in response to metabolic or environmental stresses. Mol Cancer
      Res; 16(5); 909-19. (c)2018 AACR.

PMID- 29453316
TI  - BRD1-Mediated Acetylation Promotes Integrin alphaV Gene Expression Via
      Interaction with Sulfatide.
AB  - Integrin alphaV gene expression is often dysregulated in cancers especially in
      hepatocellular carcinoma (HCC); however, the mechanism of regulation is poorly
      understood. Here, it is demonstrated that sulfatide activated integrin alphaV
      gene transcription, through histone H3K9/14 acetylation at the promoter, and high
      integrin alphaV expression are closely associated with poor prognosis. To
      elucidate the mechanism of regulation of acetylation, sulfatide-bound proteins
      were screened by mass spectrometry (MS), and bromodomain containing protein 1
      (BRD1) was identified as an interacting protein that also colocalized with
      sulfatide in HCC cells. BRD1 was also formed a complex with Sp1, which was
      recruited to the integrin alphaV gene promoter. Sulfatide was also found to
      induce BRD1, monocytic leukemia zinc finger (MOZ) and histone acetyltransferase
      binding to ORC1 (HBO1) acetyltransferase multiprotein complex recruitment to the
      integrin alphaV promoter, which is responsible for histone H3K9/14 acetylation.
      Finally, knockdown of BRD1 limited sulfatide-induced H3K9/14 acetylation and
      occupancy of MOZ or HBO1 on integrin alphaV gene promoter.Implications: This
      study demonstrates that sulfatide interaction with BRD1 mediates acetylation and
      is important for regulation of integrin alphaV gene expression. Mol Cancer Res;
      16(4); 610-22. (c)2018 AACR.

PMID- 29453317
TI  - Histone H3.3K27M Mobilizes Multiple Cancer/Testis (CT) Antigens in Pediatric
      Glioma.
AB  - Lysine to methionine mutations at position 27 (K27M) in the histone H3 (H3.3 and
      H3.1) are highly prevalent in pediatric high-grade gliomas (HGG) that arise in
      the midline of the central nervous system. H3K27M perturbs the activity of
      polycomb repressor complex 2 and correlates with DNA hypomethylation; however,
      the pathways whereby H3K27M drives the development of pediatric HGG remain poorly
      understood. To understand the mechanism of pediatric HGG development driven by
      H3.3K27M and discover potential therapeutic targets or biomarkers, we established
      pediatric glioma cell model systems harboring H3.3K27M and performed microarray
      analysis. H3.3K27M caused the upregulation of multiple cancer/testis (CT)
      antigens, such as ADAMTS1, ADAM23, SPANXA1, SPANXB1/2, IL13RA2, VCY, and VCX3A,
      in pediatric glioma cells. Chromatin immunoprecipitation analysis from H3.3K27M
      cells revealed decreased H3K27me3 levels and increased H3K4me3 levels on the
      VCX3A promoter. Knockdown of VCX3A by siRNA significantly inhibited the growth of
      pediatric glioma cells harboring H3.3K27M. Overexpression of VCX3A/B genes
      stimulated the expression of several HLA genes, including HLA-A, HLA-B, HLA-E,
      HLA-F, and HLA-G The expression of VCX3A in pediatric HGG was confirmed using a
      tissue microarray. Gene set enrichment analysis revealed that CT antigens are
      enriched in pediatric HGG clinical specimens with H3.3K27M, with the upregulation
      of IL13RA2 contributing to the enrichment significantly. These results indicate
      that the upregulation of CT antigens, such as VCX3A and IL13RA2, correlates with
      pediatric gliomagenesis. Mol Cancer Res; 16(4); 623-33. (c)2018 AACR.

PMID- 29453318
TI  - Integration of Distinct ShcA Signaling Complexes Promotes Breast Tumor Growth and
      Tyrosine Kinase Inhibitor Resistance.
AB  - The commonality between most phospho-tyrosine signaling networks is their shared
      use of adaptor proteins to transduce mitogenic signals. ShcA (SHC1) is one such
      adaptor protein that employs two phospho-tyrosine binding domains (PTB and SH2)
      and key phospho-tyrosine residues to promote mammary tumorigenesis. Receptor
      tyrosine kinases (RTK), such as ErbB2, bind the ShcA PTB domain to promote breast
      tumorigenesis by engaging Grb2 downstream of the ShcA tyrosine phosphorylation
      sites to activate AKT/mTOR signaling. However, breast tumors also rely on the
      ShcA PTB domain to bind numerous negative regulators that limit activation of
      secondary mitogenic signaling networks. This study examines the role of PTB
      independent ShcA pools in controlling breast tumor growth and resistance to
      tyrosine kinase inhibitors. We demonstrate that PTB-independent ShcA complexes
      predominately rely on the ShcA SH2 domain to activate multiple Src family kinases
      (SFK), including Src and Fyn, in ErbB2-positive breast cancers. Using genetic and
      pharmacologic approaches, we show that PTB-independent ShcA complexes augment
      mammary tumorigenesis by increasing the activity of the Src and Fyn tyrosine
      kinases in an SH2-dependent manner. This bifurcation of signaling complexes from
      distinct ShcA pools transduces non-redundant signals that integrate the AKT/mTOR
      and SFK pathways to cooperatively increase breast tumor growth and resistance to
      tyrosine kinase inhibitors, including lapatinib and PP2. This study
      mechanistically dissects how the interplay between diverse intracellular ShcA
      complexes impacts the tyrosine kinome to affect breast
      tumorigenesis.Implications: The ShcA adaptor, within distinct signaling
      complexes, impacts tyrosine kinase signaling, breast tumor growth, and resistance
      to tyrosine kinase inhibitors. Mol Cancer Res; 16(5); 894-908. (c)2018 AACR.

PMID- 29453319
TI  - Leptin Signaling Mediates Obesity-Associated CSC Enrichment and EMT in
      Preclinical TNBC Models.
AB  - Obesity is associated with poor prognosis in triple-negative breast cancer
      (TNBC). Preclinical models of TNBC were used to test the hypothesis that
      increased leptin signaling drives obesity-associated TNBC development by
      promoting cancer stem cell (CSC) enrichment and/or epithelial-to-mesenchymal
      transition (EMT). MMTV-Wnt-1 transgenic mice, which develop spontaneous basal
      like, triple-negative mammary tumors, received either a control diet (10% kcal
      from fat) or a diet-induced obesity regimen (DIO, 60% kcal from fat) for up to 42
      weeks (n = 15/group). Mice were monitored for tumor development and euthanized
      when tumor diameter reached 1.5 cm. Tumoral gene expression was assessed via RNA
      sequencing (RNA-seq). DIO mice had greater body weight and percent body fat at
      termination than controls. DIO mice, versus controls, demonstrated reduced
      survival, increased systemic metabolic and inflammatory perturbations,
      upregulated tumoral CSC/EMT gene signature, elevated tumoral aldehyde
      dehydrogenase activity (a CSC marker), and greater leptin signaling. In cell
      culture experiments using TNBC cells (murine: E-Wnt and M-Wnt; human: MDA-MB
      231), leptin enhanced mammosphere formation, and media supplemented with serum
      from DIO versus control mice increased cell viability, migration, invasion, and
      CSC- and EMT-related gene expression, including Foxc2, Twist2, Vim, Akt3, and
      Sox2 In E-Wnt cells, knockdown of leptin receptor ablated these procancer effects
      induced by DIO mouse serum. These findings indicate that increased leptin
      signaling is causally linked to obesity-associated TNBC development by promoting
      CSC enrichment and EMT.Implications: Leptin-associated signals impacting CSC and
      EMT may provide new targets and intervention strategies for decreasing TNBC
      burden in obese women. Mol Cancer Res; 16(5); 869-79. (c)2018 AACR.

PMID- 29453320
TI  - Methylation of the HOXA10 Promoter Directs miR-196b-5p-Dependent Cell
      Proliferation and Invasion of Gastric Cancer Cells.
AB  - The cross-talk between epigenetics and miRNA expression plays an important role
      in human tumorigenesis. Herein, the regulation and role of miR-196b-5p in gastric
      cancer was investigated. qRT-PCR demonstrated that miR-196b-5p is significantly
      overexpressed in human gastric cancer tissues (P < 0.01). In addition, it was
      determined that HOXA10, a homeobox family member and host gene for miR-196b-5p,
      is overexpressed and positively correlated with miR-196b-5p expression levels (P
      < 0.001). Quantitative pyrosequencing methylation analysis demonstrated
      significantly lower levels of DNA methylation at the HOXA10 promoter in gastric
      cancer, as compared with nonneoplastic gastric mucosa specimens. 5-Aza-2'
      deoxycytidine treatment confirmed that demethylation of HOXA10 promoter induces
      the expression of HOXA10 and miR-196b-5p in gastric cancer cell model systems.
      Using the Tff1 knockout mouse model of gastric neoplasia, hypomethylation and
      overexpression of HOXA10 and miR-196b-5p in gastric tumors was observed, as
      compared with normal gastric mucosa from Tff1 wild-type mice. Mechanistically,
      reconstitution of TFF1 in human gastric cancer cells led to an increased HOXA10
      promoter methylation with reduced expression of HOXA10 and miR-196b-5p.
      Functionally, miR-196b-5p reconstitution promoted human gastric cancer cell
      proliferation and invasion in vitro In summary, the current data demonstrate
      overexpression of miR-196b-5p in gastric cancer and suggest that TFF1 plays an
      important role in suppressing the expression of miR-196b-5p by mediating DNA
      methylation of the HOXA10 promoter. Loss of TFF1 expression may promote
      proliferation and invasion of gastric cancer cells through induction of promoter
      hypomethylation and expression of the HOXA10/miR-196b-5p axis.Implications: This
      study indicates that loss of TFF1 promotes the aberrant overexpression of HOXA10
      and miR-196b-5p by demethylation of the HOXA10 promoter, which provides a new
      perspective of TFF1/HOXA10/miR-196b-5p functions in human gastric cancer. Mol
      Cancer Res; 16(4); 696-706. (c)2018 AACR.

PMID- 29453321
TI  - Inhibition of CD95/CD95L (FAS/FASLG) Signaling with APG101 Prevents Invasion and
      Enhances Radiation Therapy for Glioblastoma.
AB  - CD95 (Fas/APO-1), a death receptor family member, activity has been linked to
      tumorigenicity in multiple cancers, including glioblastoma multiforme (GBM). A
      phase II clinical trial on relapsed glioblastoma patients demonstrated that
      targeted inhibition of CD95 signaling via the CD95 ligand (CD95L) binding and
      neutralizing Fc-fusion protein APG101 (asunercept) prolonged patient survival.
      Although CD95 signaling may be relevant for multiple aspects of tumor growth, the
      mechanism of action of APG101 in glioblastoma is not clear. APG101 action was
      examined by in vitro proliferation, apoptosis, and invasion assays with human and
      murine glioma and human microglial cells, as well as in vivo therapy studies with
      orthotopic gliomas and clinical data. APG101 inhibits CD95L-mediated invasion of
      glioma cells. APG101 treatment was effective in glioma-bearing mice,
      independently of the presence or absence of CD4 and CD8 T lymphocytes, which
      should be sensitive to CD95L. Combined with radiotherapy, APG101 demonstrated a
      reduction of tumor growth, fewer tumor satellites, reduced activity of matrix
      metalloproteinases (MMP) as well as prolonged survival of tumor-bearing mice
      compared with radiotherapy alone. Inhibiting rather than inducing CD95 activity
      is a break-of-paradigm therapeutic approach for malignant gliomas. Evidence, both
      in vitro and in vivo, is provided that CD95L-binding fusion protein treatment
      enhanced the efficacy of radiotherapy and reduced unwanted proinfiltrative
      effects by reducing metalloproteinase activity by directly affecting the tumor
      cells.Implications: APG101 (asunercept) successfully used in a controlled phase
      II glioblastoma trial (NCT01071837) acts anti-invasively by inhibiting matrix
      metalloproteinase signaling, resulting in additive effects together with
      radiotherapy and helping to further develop a treatment for this devastating
      disease. Mol Cancer Res; 16(5); 767-76. (c)2018 AACR.

PMID- 29453322
TI  - The mTOR Targets 4E-BP1/2 Restrain Tumor Growth and Promote Hypoxia Tolerance in
      PTEN-driven Prostate Cancer.
AB  - The mTOR signaling pathway is a central regulator of protein synthesis and
      cellular metabolism in response to the availability of energy, nutrients, oxygen,
      and growth factors. mTOR activation leads to phosphorylation of multiple
      downstream targets including the eukaryotic initiation factor 4E (eIF4E) binding
      proteins-1 and -2 (EIF4EBP1/4E-BP1 and EIF4EBP2/4E-BP2). These binding proteins
      inhibit protein synthesis, but are inactivated by mTOR to stimulate cell growth
      and metabolism. However, the role of these proteins in the context of aberrant
      activation of mTOR, which occurs frequently in cancers through loss of PTEN or
      mutational activation of the PI3K/AKT pathway, is unclear. Here, even under
      conditions of aberrant mTOR activation, hypoxia causes dephosphorylation of 4E
      BP1/4E-BP2 and increases their association with eIF4E to suppress translation.
      This is essential for hypoxia tolerance as knockdown of 4E-BP1 and 4E-BP2
      decreases proliferation under hypoxia and increases hypoxia-induced cell death.
      In addition, genetic deletion of 4E-BP1 and 4E-BP2 significantly accelerates all
      phases of cancer development in the context of PTEN loss-driven prostate cancer
      in mice despite potent PI3K/AKT and mTOR activation. However, even with a more
      rapid onset, tumors that establish in the absence of 4E-BP1 and 4E-BP2 have
      reduced levels of tumor hypoxia and show increased cell death within hypoxic
      tumor regions. Together, these data demonstrate that 4E-BP1 and 4E-BP2 act as
      essential metabolic breaks even in the context of aberrant mTOR activation and
      that they are essential for the creation of hypoxia-tolerant cells in prostate
      cancer. Mol Cancer Res; 16(4); 682-95. (c)2018 AACR.

PMID- 29453324
TI  - Incidence and Predictors of Perioperative Complications With Transvenous Lead
      Extractions: Real-World Experience With National Cardiovascular Data Registry.
AB  - BACKGROUND: Transvenous lead extraction is an integral part of management of
      patients with cardiovascular implantable electronic devices. Real-world incidence
      and predictors of perioperative complications in extractions involving
      implantable cardioverter-defibrillator leads have not been described in detail.
      METHODS AND RESULTS: Data from the National Cardiovascular Data Registry
      Implantable Cardioverter-Defibrillator Registry were analyzed. Lead extraction
      was defined as removal of leads implanted for >1 year. Predictors of major
      perioperative complications for all extraction procedures (11 304) and for high
      voltage lead (8362, 74%), across 762 centers, were analyzed using univariate and
      multivariate logistic regression. Major complication occurred in 258 (2.3%)
      extraction procedures. Of these 258 with a complication, 41 (16%) required urgent
      cardiac surgery. Of these 41, 14 (34%) died during surgery. Among the total 98
      (0.9%) deaths reported, 18 (0.16% of total) occurred during transvenous lead
      extraction. In multivariable logistic regression analysis, female sex, admission
      other than electively for procedure, >=3 leads extracted, longer implant
      duration, dislodgement of other leads, and patient's clinical status requiring
      lead extraction (infection/perforation) were associated with increased risk of
      complications. Smaller lead diameter, flat versus round coil shape, and greater
      proximal surface coil area were multivariate predictors of major perioperative
      complications specific to high-voltage leads. CONCLUSIONS: The rate of major
      complications and mortality with transvenous lead extraction is similar in the
      real-world outcomes to that reported in recent single-center studies from high
      volume centers. There is significant risk of urgent cardiac surgery, which
      carries a high mortality, and planning for appropriate cardiothoracic surgery
      backup is imperative.

PMID- 29453323
TI  - RNA-stabilization factors in chloroplasts of vascular plants.
AB  - In contrast to the cyanobacterial ancestor, chloroplast gene expression is
      predominantly governed on the post-transcriptional level such as modifications of
      the RNA sequence, decay rates, exo- and endonucleolytic processing as well as
      translational events. The concerted function of numerous chloroplast RNA-binding
      proteins plays a fundamental and often essential role in all these processes but
      our understanding of their impact in regulation of RNA degradation is only at the
      beginning. Moreover, metabolic processes and post-translational modifications are
      thought to affect the function of RNA protectors. These protectors contain a
      variety of different RNA-recognition motifs, which often appear as multiple
      repeats. They are required for normal plant growth and development as well as
      diverse stress responses and acclimation processes. Interestingly, most of the
      protectors are plant specific which reflects a fast-evolving RNA metabolism in
      chloroplasts congruent with the diverging RNA targets. Here, we mainly focused on
      the characteristics of known chloroplast RNA-binding proteins that protect
      exonuclease-sensitive sites in chloroplasts of vascular plants.

PMID- 29453325
TI  - Performance of the 2015 International Task Force Consensus Statement Risk
      Stratification Algorithm for Implantable Cardioverter-Defibrillator Placement in
      Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.
AB  - BACKGROUND: Ventricular arrhythmias are a feared complication of arrhythmogenic
      right ventricular dysplasia/cardiomyopathy. In 2015, an International Task Force
      Consensus Statement proposed a risk stratification algorithm for implantable
      cardioverter-defibrillator placement in arrhythmogenic right ventricular
      dysplasia/cardiomyopathy. METHODS AND RESULTS: To evaluate performance of the
      algorithm, 365 arrhythmogenic right ventricular dysplasia/cardiomyopathy patients
      were classified as having a Class I, IIa, IIb, or III indication per the
      algorithm at baseline. Survival free from sustained ventricular arrhythmia
      (VT/VF) in follow-up was the primary outcome. Incidence of ventricular
      fibrillation/flutter cycle length <240 ms was also assessed. Two hundred twenty
      four (61%) patients had a Class I implantable cardioverter-defibrillator
      indication; 80 (22%), Class IIa; 54 (15%), Class IIb; and 7 (2%), Class III.
      During a median 4.2 (interquartile range, 1.7-8.4)-year follow-up, 190 (52%)
      patients had VT/VF and 60 (16%) had ventricular fibrillation/flutter. Although
      the algorithm appropriately differentiated risk of VT/VF, incidence of VT/VF was
      underestimated (observed versus expected: 29.6 [95% confidence interval, 25.2
      34.0] versus >10%/year Class I; 15.5 [confidence interval 11.1-21.6] versus 1% to
      10%/year Class IIa). In addition, the algorithm did not differentiate survival
      free from ventricular fibrillation/flutter between Class I and IIa patients
      (P=0.97) or for VT/VF in Class I and IIa primary prevention patients (P=0.22).
      Adding Holter results (<1000 premature ventricular contractions/24 hours) to
      International Task Force Consensus classification differentiated risks.
      CONCLUSIONS: While the algorithm differentiates arrhythmic risk well overall, it
      did not distinguish ventricular fibrillation/flutter risks of patients with Class
      I and IIa implantable cardioverter-defibrillator indications. Limited
      differentiation was seen for primary prevention cases. As these are vital
      uncertainties in clinical decision-making, refinements to the algorithm are
      suggested prior to implementation.

PMID- 29453326
TI  - Lead Extraction Through a Wide-Angle Lens.

PMID- 29453327
TI  - Arrhythmic Risk Stratification for Arrhythmogenic Right Ventricular
      Cardiomyopathy: Should We Ask Who Is at High Risk or Who Is at Low Risk?

PMID- 29453328
TI  - Management of atrial fibrillation in patients with rheumatic mitral stenosis.
AB  - Atrial fibrillation (AF) is frequent in patients with rheumatic mitral stenosis
      (MS). Pressure overload leads to marked structural and electrical remodelling of
      left atrium. The frequency of persistent AF increases with age and paroxysmal,
      asymptomatic, AF seems even more frequent. The occurrence of AF worsens the
      haemodynamic tolerance of MS and markedly increases the risk of thromboembolic
      events. AF has a negative impact on the natural history of MS and on its outcome
      after commissurotomy. The respective indications of rhythm and rate control
      should be adapted to patient characteristics, particularly the consequences of
      MS, and take into account the high risk of recurrence of AF. Oral anticoagulant
      therapy is mandatory when AF complicates MS, regardless of its severity and
      CHA2DS2-VASc score. Non-vitamin K antagonists oral anticoagulants are not
      recommended in moderate-to-severe MS due to the lack of data. Percutaneous mitral
      commissurotomy does not appear to prevent the occurrence of AF in MS but should
      be considered as the first-line therapy when AF is associated with severe
      symptomatic MS, followed by the discussion of cardioversion or ablation. AF
      ablation should be considered in patients with mitral disease requiring
      intervention, but the ideal timing and techniques are difficult to determine due
      to the lack of appropriate specific randomised trials in patients with MS.

PMID- 29453329
TI  - Management, characteristics and outcomes of patients with acute coronary syndrome
      in Sri Lanka.
AB  - BACKGROUND: Ischaemic heart disease is the leading cause of in-hospital mortality
      in Sri Lanka. Acute Coronary Syndrome Sri Lanka Audit Project (ACSSLAP) is the
      first national clinical-audit project that evaluated patient characteristics,
      clinical outcomes and care provided by state-sector hospitals. METHODS: ACSSLAP
      prospectively evaluated acute care, in-hospital care and discharge plans provided
      by all state-sector hospitals managing patients with ACS. Data were collected
      from 30 consecutive patients from each hospital during 2-4 weeks window. Local
      and international recommendations were used as audit standards. RESULTS: Data
      from 87/98 (88.7%) hospitals recruited 2177 patients, with 2116 confirmed as
      having ACS. Mean age was 61.4+/-11.8 years (range 20-95) and 58.7% (n=1242) were
      males. There were 813 (38.4%) patients with unstable angina, 695 (32.8%) with non
      ST-elevation myocardial infarction (NSTEMI) and 608 (28.7%) with ST-elevation
      myocardial infarction (STEMI). Both STEMI (69.9%) and NSTEMI (61.4%) were more in
      males (P<0.001). Aspirin, clopidogrel and statins were given to over 90% in acute
      setting and on discharge. In STEMI, 407 (66.9%) were reperfused; 384 (63.2%) were
      given fibrinolytics and only 23 (3.8%) underwent primary percutaneous coronary
      intervention (PCI). Only 42.3 % had thrombolysis in <30 min and 62.5% had PCI in
      <90 min. On discharge, beta-blockers and ACE inhibitors/angiotensin II receptor
      blockers were given to only 50.7% and 69.2%, respectively and only 17.6% had
      coronary interventions planned. CONCLUSIONS: In patients with ACS, aspirin,
      clopidogrel and statin use met audit standards in acute setting and on discharge.
      Vast majority of patients with STEMI underwent fibrinolyisis than PCI, due to
      limited resources. Primary PCI, planned coronary interventions and timely
      thrombolysis need improvement in Sri Lanka.

PMID- 29453330
TI  - Interphysician agreement on subclassification of myocardial infarction.
AB  - OBJECTIVE: The universal definition of myocardial infarction (MI) differentiates
      MI due to oxygen supply/demand mismatch (type 2) from MI due to plaque rupture
      (type 1) as well as from myocardial injuries of non-ischaemic or multifactorial
      nature. The purpose of this study was to investigate how often physicians agree
      in this classification and what factors lead to agreement or disagreement.
      METHODS: A total of 1328 patients diagnosed with MI at eight different Swedish
      hospitals 2011 were included. All patients were retrospectively reclassified into
      different MI or myocardial injury subtypes by two independent specially trained
      physicians, strictly adhering to the third universal definition of MI. RESULTS:
      Overall, there was a moderate interobserver agreement with a kappa coefficient
      (kappa) of 0.55 in this classification. There was substantial agreement when
      distinguishing type 1 MI (kappa: 0.61), compared with moderate agreement when
      distinguishing type 2 MI (kappa: 0.54). In multivariate logistic regression
      analyses, ST elevation MI (P<0.001), performed coronary angiography (P<0.001) and
      larger changes in troponin levels (P=0.023) independently made the physicians
      agree significantly more often, while they disagreed more often with symptoms of
      dyspnoea (P<0.001), higher systolic blood pressure (P=0.001) and higher C
      reactive protein levels on admission (P=0.016). CONCLUSION: Distinguishing MI
      types is challenging also for trained adjudicators. Although strictly adhering to
      the third universal definition of MI, differentiation between type 1 MI, type 2
      MI and myocardial injury only gave a moderate rate of interobserver agreement.
      More precise and clinically applicable criteria for the current classification,
      particularly for type 2 MI diagnosis, are urgently needed.

PMID- 29453331
TI  - A Prospective Cohort Evaluation of the Cortisol Response to Cardiac Surgery with
      Occurrence of Early Postoperative Cognitive Decline.
AB  - BACKGROUND A recent study reported that patients with higher cortisol levels on
      the 1st postoperative morning after cardiac surgery exhibited an increased risk
      of early postoperative cognitive decline (POCD). Therefore, we conducted the
      current study to gain further insight into the stress response to a surgical
      procedure as a potential risk factor for early POCD after cardiac surgery.
      MATERIAL AND METHODS This prospective cohort study enrolled 125 patients
      undergoing elective cardiac surgery with or without cardiopulmonary bypass (CPB).
      Patient serum cortisol levels were determined 1 day before surgery (at 08: 00)
      and on the 1st (at 08: 00, 16: 00 and 24: 00), 3rd (at 08: 00), and 5th (at 08:
      00) postoperative days. A battery of 9 neuropsychological tests were used to
      assess the participants 2 days before the surgical procedure and on the 6th
      postoperative day. POCD was defined as a decrease in performance of 1 SD or
      greater between the postoperative and preoperative z scores on at least 1
      neuropsychological test. A mixed-design ANOVA was used to determine the
      correlations of the perioperative cortisol levels with the occurrence of POCD and
      with the surgical technique performed. RESULTS Mixed-design ANOVA showed no
      statistically significant differences in the cortisol levels between non-POCD and
      POCD patients (F=0.52, P=0.690) or between patients with and without CPB (F=2.02,
      P=0.103) at the 6 perioperative time points. CONCLUSIONS The occurrence of early
      POCD and the use of CPB were not associated with significantly higher cortisol
      levels in the repeated measurement design.

PMID- 29453332
TI  - Step-wise evolution of complex chemical defenses in millipedes: a phylogenomic
      approach.
AB  - With fossil representatives from the Silurian capable of respiring atmospheric
      oxygen, millipedes are among the oldest terrestrial animals, and likely the first
      to acquire diverse and complex chemical defenses against predators. Exploring the
      origin of complex adaptive traits is critical for understanding the evolution of
      Earth's biological complexity, and chemical defense evolution serves as an ideal
      study system. The classic explanation for the evolution of complexity is by
      gradual increase from simple to complex, passing through intermediate "stepping
      stone" states. Here we present the first phylogenetic-based study of the
      evolution of complex chemical defenses in millipedes by generating the largest
      genomic-based phylogenetic dataset ever assembled for the group. Our phylogenomic
      results demonstrate that chemical complexity shows a clear pattern of escalation
      through time. New pathways are added in a stepwise pattern, leading to greater
      chemical complexity, independently in a number of derived lineages. This
      complexity gradually increased through time, leading to the advent of three
      distantly related chemically complex evolutionary lineages, each uniquely
      characteristic of each of the respective millipede groups.

PMID- 29453333
TI  - Scleraxis is a transcriptional activator that regulates the expression of
      Tenomodulin, a marker of mature tenocytes and ligamentocytes.
AB  - Tenomodulin (Tnmd) is a type II transmembrane glycoprotein predominantly
      expressed in tendons and ligaments. We found that scleraxis (Scx), a member of
      the Twist-family of basic helix-loop-helix transcription factors, is a
      transcriptional activator of Tnmd expression in tenocytes. During embryonic
      development, Scx expression preceded that of Tnmd. Tnmd expression was nearly
      absent in tendons and ligaments of Scx-deficient mice generated by transcription
      activator-like effector nucleases-mediated gene disruption. Tnmd mRNA levels were
      dramatically decreased during serial passages of rat tenocytes. Scx silencing by
      small interfering RNA significantly suppressed endogenous Tnmd mRNA levels in
      tenocytes. Mouse Tnmd contains five E-box sites in the ~1-kb 5'-flanking region.
      A 174-base pair genomic fragment containing a TATA box drives transcription in
      tenocytes. Enhancer activity was increased in the upstream region (-1030 to -295)
      of Tnmd in tenocytes, but not in NIH3T3 and C3H10T1/2 cells. Preferential binding
      of both Scx and Twist1 as a heterodimer with E12 or E47 to CAGATG or CATCTG and
      transactivation of the 5'-flanking region were confirmed by electrophoresis
      mobility shift and dual luciferase assays, respectively. Scx directly
      transactivates Tnmd via these E-boxes to positively regulate tenocyte
      differentiation and maturation.

PMID- 29453335
TI  - High-definition and low-noise muography of the Sakurajima volcano with gaseous
      tracking detectors.
AB  - Muography is a novel method to highly resolve the internal structure of active
      volcanoes by taking advantage of the cosmic muon's strong penetration power. In
      this paper, we present the first high-definition image in the vicinity of craters
      of an erupting volcano called Sakurajima, Kyushu, Japan. The muography
      observation system based on the technique of multi-wire proportional chamber
      (mMOS) has been operated reliably during the data taking period of 157 days. The
      mMOS measured precisely the flux of muons up to the thickness of 5,000 meter
      water-equivalent. It was shown that high-definition density maps around the
      Craters A, B and Showa could be determined with a precision of less than 7.5 *
      7.5 m2 which earlier had not yet been achieved. The observed density distribution
      suggests that the fall back deposits filled the magma pathway and increased their
      density underneath Craters A and B.

PMID- 29453334
TI  - beta-catenin-independent regulation of Wnt target genes by RoR2 and ATF2/ATF4 in
      colon cancer cells.
AB  - Wnt signaling is an evolutionarily conserved signaling route required for
      development and homeostasis. While canonical, beta-catenin-dependent Wnt
      signaling is well studied and has been linked to many forms of cancer, much less
      is known about the role of non-canonical, beta-catenin-independent Wnt signaling.
      Here, we aimed at identifying a beta-catenin-independent Wnt target gene
      signature in order to understand the functional significance of non-canonical
      signaling in colon cancer cells. Gene expression profiling was performed after
      silencing of key components of Wnt signaling pathway and an iterative signature
      algorithm was applied to predict pathway-dependent gene signatures. Independent
      experiments confirmed several target genes, including PLOD2, HADH, LCOR and REEP1
      as non-canonical target genes in various colon cancer cells. Moreover, non
      canonical Wnt target genes are regulated via RoR2, Dvl2, ATF2 and ATF4.
      Furthermore, we show that the ligands Wnt5a/b are upstream regulators of the non
      canonical signature and moreover regulate proliferation of cancer cells in a beta
      catenin-independent manner. Our experiments indicate that colon cancer cells are
      dependent on both beta-catenin-dependent and -independent Wnt signaling routes
      for growth and proliferation.

PMID- 29453338
TI  - Revisiting the Pacific Meridional Mode.
AB  - Numerous studies demonstrated that the Pacific Meridional Mode (PMM) can excite
      Central Pacific (CP) El Nino-Southern Oscillation (ENSO) events and that the PMM
      is mostly a stochastic phenomenon associated with mid-latitude atmospheric
      variability and wind-evaporation-SST feedback. Here we show that CP sea surface
      temperature (SST) variability exhibits high instantaneous correlations both on
      interannual (ENSO-related) and decadal (Pacific Decadal Oscillation (PDO)
      related) timescales with the PMM. By prescribing an idealized interannual
      equatorial CP ENSO SST forcing in a partially-coupled atmosphere/slab ocean model
      we are able to generate a realistic instantaneous PMM response consistent with
      the observed statistical ENSO/PMM relationship. This means that CP ENSO and the
      PMM can excite each other respectively on interannual timescales, strongly
      suggesting that a fast positive feedback exists between the two phenomena. Thus,
      we argue that they cannot be considered two independent dynamical entities.
      Additionally, we show that the interannual CP ENSO SST forcing generates
      atmospheric circulation variability that projects strongly on the Aleutian Low
      and North Pacific SST anomalies that exhibit the characteristic PDO pattern.

PMID- 29453336
TI  - Alternative splicing of ALCAM enables tunable regulation of cell-cell adhesion
      through differential proteolysis.
AB  - While many adhesion receptors are known to influence tumor progression, the
      mechanisms by which they dynamically regulate cell-cell adhesion remain elusive.
      We previously identified Activated Leukocyte Cell Adhesion Molecule (ALCAM) as a
      clinically relevant driver of metastasis and hypothesized that a tunable
      mechanism of ectodomain shedding regulates its contribution to dissemination. To
      test this hypothesis, we examined an under-explored ALCAM splice variant (ALCAM
      Iso2) and demonstrated that loss of the membrane-proximal region of ALCAM (exon
      13) increased metastasis four-fold. Mechanistic studies identified a novel MMP14
      dependent membrane distal cleavage site in ALCAM-Iso2, which mediated a ten-fold
      increase in shedding, thereby decreasing cellular cohesion. Importantly, the loss
      of cohesion is not limited to the cell capable of shedding because the released
      extracellular domain diminished cohesion of non-shedding cells through disruption
      of ALCAM-ALCAM interactions. ALCAM-Iso2-dominated expression in bladder cancer
      tissue, compared to normal bladder, further emphasizes that ALCAM alternative
      splicing may contribute to clinical disease progression. The requirement for both
      the loss of exon 13 and the gain of metalloprotease activity suggests that ALCAM
      shedding and concomitant regulation of tumor cell adhesion is a locally tunable
      process.

PMID- 29453337
TI  - p66Shc Signaling Mediates Diabetes-Related Cognitive Decline.
AB  - Accumlating evidence have suggested that diabetes mellitus links dementia,
      notably of Alzheimer's disease (AD). However, the underlying mechanism remains
      unclear. Several studies have shown oxidative stress (OS) to be one of the major
      factors in the pathogenesis of diabetic complications. Here we show OS
      involvement in brain damage in a diabetic animal model that is at least partially
      mediated through an AD-pathology-independent mechanism apart from amyloid-beta
      accumulation. We investigated the contribution of the p66Shc signaling pathway to
      diabetes-related cognitive decline using p66Shc knockout (-/-) mice. p66Shc (-/-)
      mice have less OS in the brain and are resistant to diabetes-induced brain
      damage. Moreover, p66Shc (-/-) diabetic mice show significantly less cognitive
      dysfunction and decreased levels of OS and the numbers of microglia. This study
      postulates a p66Shc-mediated inflammatory cascade leading to OS as a causative
      pathogenic mechanism in diabetes-associated cognitive impairment that is at least
      partially mediated through an AD-pathology-independent mechanism.

PMID- 29453340
TI  - Elevated nitrogen allows the weak invasive plant Galinsoga quadriradiata to
      become more vigorous with respect to inter-specific competition.
AB  - Elevated nitrogen associated with global change is believed to promote the
      invasion of many vigorous exotic plants. However, it is unclear how a weak exotic
      plant will respond to elevated nitrogen in the future. In this study, the
      competitive outcome of a weak invasive plant (Galinsoga quadriradiata) and two
      non-invasive plants was detected. The plants were subjected to 3 types of culture
      (mixed, monoculture or one-plant), 2 levels of nitrogen (ambient or elevated at a
      rate of 2 g m-2 yr-1) and 2 levels of light (65% shade or full sunlight). The
      results showed that elevated nitrogen significantly promoted the growth of both
      the weak invader and the non-invasive plants in one-plant pots; however, growth
      promotion was not observed for the non-invasive species in the mixed culture
      pots. The presence of G. quadriradiata significantly inhibited the growth of the
      non-invasive plants, and a decreased negative species interaction was detected as
      a result of elevated nitrogen. Our results suggest that competitive interactions
      between G. quadriradiata and the non-invasive plants were altered by elevated
      nitrogen. It provides exceptional evidence that an initially weak invasive plant
      can become an aggressive invader through elevated nitrogen deposition.

PMID- 29453339
TI  - A role for tau in learning, memory and synaptic plasticity.
AB  - Tau plays a pivotal role in the pathogenesis of neurodegenerative disorders:
      mutations in the gene encoding for tau (MAPT) are linked to Fronto-temporal
      Dementia (FTD) and hyper-phosphorylated aggregates of tau forming neurofibrillary
      tangles (NFTs) that constitute a pathological hallmark of Alzheimer disease (AD)
      and FTD. Accordingly, tau is a favored therapeutic target for the treatment of
      these diseases. Given the criticality of tau to dementia's pathogenesis and
      therapy, it is important to understand the physiological function of tau in the
      central nervous system. Analysis of Mapt knock out (Mapt-/-) mice has yielded
      inconsistent results. Some studies have shown that tau deletion does not alter
      memory while others have described synaptic plasticity and memory alterations in
      Mapt-/- mice. To help clarifying these contrasting results, we analyzed a
      distinct Mapt-/- model on a B6129PF3/J genetic background. We found that tau
      deletion leads to aging-dependent short-term memory deficits, hyperactivity and
      synaptic plasticity defects. In contrast, Mapt+/- mice only showed a mild short
      memory deficit in the novel object recognition task. Thus, while tau is important
      for normal neuronal functions underlying learning and memory, partial reduction
      of tau expression may have fractional deleterious effects.

PMID- 29453341
TI  - Transcriptomics reveals a cross-modulatory effect between riboflavin and iron and
      outlines responses to riboflavin biosynthesis and uptake in Vibrio cholerae.
AB  - Vibrio cholerae, a pandemic diarrheagenic bacterium, is able to synthesize the
      essential vitamin riboflavin through the riboflavin biosynthetic pathway (RBP)
      and also to internalize it through the RibN importer. In bacteria, the way
      riboflavin biosynthesis and uptake functions correlate is unclear. To gain
      insights into the role of the riboflavin provision pathways in the physiology of
      V. cholerae, we analyzed the transcriptomics response to extracellular riboflavin
      and to deletions of ribD (RBP-deficient strain) or ribN. Many riboflavin
      responsive genes were previously reported to belong to the iron regulon,
      including various iron uptake genes. Real time PCR analysis confirmed this effect
      and further documented that reciprocally, iron regulates RBP and ribN genes in a
      riboflavin-dependent way. A subset of genes were responding to both ribD and ribN
      deletions. However, in the subset of genes specifically affected in the ?ribD
      strain, the functional terms protein folding and oxidation reduction process were
      enriched, as determined by a Gene Ontology analysis. In the gene subset
      specifically affected in the ?ribN strain, the cytochrome complex assembly
      functional term was enriched. Results suggest that iron and riboflavin
      interrelate to regulate its respective provision genes and that both common and
      specific effects of biosynthesized and internalized riboflavin exist.

PMID- 29453342
TI  - Prediction of coronary disease incidence by biomarkers of inflammation,
      oxidation, and metabolism.
AB  - The effect of circulating biomarkers in predicting coronary artery disease (CAD)
      is not fully elucidated. This study aimed to determine the relationship with CAD
      and the predictive capacity of nine biomarkers of inflammation (TNF-alpha, IL-10,
      IL-6, MCP-1, CRP), oxidation (GHS-Px), and metabolism (adiponectin, leptin, and
      insulin). This was a case-cohort study, within the REGICOR population-cohorts
      (North-Eastern Spain), of 105 CAD cases and 638 individuals randomly selected
      from a cohort of 5,404 participants aged 35-74 years (mean follow-up = 6.1
      years). Biomarkers' hazard ratio (HR)/standard deviation was estimated with Cox
      models adjusted for age, sex, and classical risk factors. Discrimination
      improvement and reclassification were analyzed with the c-index and the Net
      reclassification index (NRI). GHS-Px (adjusted HRs = 0.77; 95%CI:0.60-0.99),
      insulin (1.46; 1.08-1.98), leptin (1.40; 1.03-1.90), IL-6 (1.34; 1.03-1.74), and
      TNF-alpha (1.80; 1.26-2.57) were significantly associated with CAD incidence. In
      the model adjusted for all biomarkers, TNF-alpha (1.87;1.31-2.66) and insulin
      (1.59;1.16-2.19) were independently associated with CAD. This final model,
      compared to a model without biomarkers, showed a c-index difference of 1.3% (
      0.7, 3.2) and a continuous NRI of 33.7% (2.6, 61.9). TNF-alpha and insulin are
      independently associated with CAD incidence and they improve reclassification
      when added to a model including classical risk factors.

PMID- 29453343
TI  - Effect of chronic exercise on fluoride metabolism in fluorosis-susceptible mice
      exposed to high fluoride.
AB  - The present study investigated the effect of chronic exercise on fluoride (F)
      metabolism in fluorosis-susceptible mice exposed to high-F and explored the
      relationship between F concentrations in bone and plasma. Thirty male mice were
      randomised into three groups: Group I (No-F, No-Exercise), Group II (50 ppmF, No
      Exercise), Group III (50 ppmF, Exercise). Body weight and physical performance of
      all mice were measured at baseline and end of experiment. F concentrations of
      plasma and bone were measured at the end of experiment. Mean plasma F
      concentration was significantly higher (p < 0.001) in Groups II and III compared
      with Group I. Mean bone F concentration was also significantly higher (p < 0.01)
      in Groups II and III compared with Group I. There was a significant correlation
      (p = 0.01, r = 0.54) between F concentration of plasma and bone. Mean body weight
      of Group I mice was significantly higher than Group II (p < 0.001) and Group III
      (p = 0.001) mice at the end of the experiment. This study, which provides the
      first data on the effect of chronic exercise on F metabolism in fluorosis
      susceptible mice, suggests no effect of chronic exercise on F in plasma and bone.
      However, exposure to high-F resulted in lower body weight and exercise capacity
      in mice.

PMID- 29453344
TI  - Giant electrocaloric and energy storage performance of [(K0.5Na0.5)NbO3](1-x)
      [LiSbO3] x nanocrystalline ceramics.
AB  - Electrocaloric (EC) refrigeration, an EC effect based technology has been
      accepted as an auspicious way in the development of next generation refrigeration
      due to high efficiency and compact size. Here, we report the results of our
      experimental investigations on electrocaloric response and electrical energy
      storage properties in lead-free nanocrystalline (1 - x)K0.5Na0.5NbO3-xLiSbO3 (KNN
      xLS) ceramics in the range of 0.015 <= x <= 0.06 by the indirect EC measurements.
      Doping of LiSbO3 has lowered both the transitions (T C and TO-T) of KNN to the
      room temperature side effectively. A maximal value of EC temperature change,
      DeltaT = 3.33 K was obtained for the composition with x = 0.03 at 345 K under an
      external electric field of 40 kV/cm. The higher value of EC responsivity, zeta =
      8.32 * 10-7 K.m/V is found with COP of 8.14 and recoverable energy storage of
      0.128 J/cm3 with 46% efficiency for the composition of x = 0.03. Our
      investigations show that this material is a very promising candidate for
      electrocaloric refrigeration and energy storage near room temperature.

PMID- 29453345
TI  - Short-term acclimation in adults does not predict offspring acclimation potential
      to hypoxia.
AB  - The prevalence of hypoxic areas in coastal waters is predicted to increase and
      lead to reduced biodiversity. While the adult stages of many estuarine
      invertebrates can cope with short periods of hypoxia, it remains unclear whether
      that ability is present if animals are bred and reared under chronic hypoxia. We
      firstly investigated the effect of moderate, short-term environmental hypoxia
      (40% air saturation for one week) on metabolic performance in adults of an
      estuarine amphipod, and the fitness consequences of prolonged exposure. We then
      reared the offspring of hypoxia-exposed parents under hypoxia, and assessed their
      oxyregulatory ability under declining oxygen tensions as juveniles and adults.
      Adults from the parental generation were able to acclimate their metabolism to
      hypoxia after one week, employing mechanisms typically associated with prolonged
      exposure. Their progeny, however, did not develop the adult pattern of
      respiratory regulation when reared under chronic hypoxia, but instead exhibited a
      poorer oxyregulatory ability than their parents. We conclude that species
      apparently hypoxia-tolerant when tested in short-term experiments, could be
      physiologically compromised as adults if they develop under hypoxia.
      Consequently, we propose that the increased prevalence of hypoxia in coastal
      regions will have marked effects in some species currently considered hypoxia
      tolerant.

PMID- 29453346
TI  - Anti-inflammatory effect of Tauroursodeoxycholic acid in RAW 264.7 macrophages,
      Bone marrow-derived macrophages, BV2 microglial cells, and spinal cord injury.
AB  - This study aimed to investigate the anti-inflammatory effects of
      tauroursodeoxycholic acid (TUDCA) after spinal cord injury (SCI) in rats. We
      induced an inflammatory process in RAW 264.7 macrophages, BV2 microglial cells,
      and bone marrow-derived macrophages (BMM) using lipopolysaccharide (LPS). The
      anti-inflammatory effects of TUDCA on LPS-stimulated RAW 264.7 macrophages, BV2
      microglial cells, and BMMs were analyzed using nitric oxide (NO) assays,
      quantitative real-time polymerase chain reactions (qRT-PCR), and enzyme-linked
      immunosorbent assays (ELISA). The pathological changes in lesions of the spinal
      cord tissue were evaluated by hematoxylin & eosin (H&E) staining, luxol fast
      blue/cresyl violet-staining and immunofluorescent staining. TUDCA decreased the
      LPS-stimulated inflammatory mediator, NO. It also suppressed pro-inflammatory
      cytokines of tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL
      1beta), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in
      both mRNA and protein levels. In addition, TUDCA decreased prostaglandin E2
      (PGE2). After SCI, TUDCA supported the recovery of the injury site and suppressed
      the expression of inflammatory cytokines such as iNOS, CD68 and CD86. In
      addition, TUDCA induced the expression of anti-inflammatory cytokine, Arg-1. In
      conclusion, TUDCA inhibits inflammatory responses in RAW 264.7 macrophages, BV2
      microglial cells, and BMMs. TUDCA can be a potential alternative drug for SCI.

PMID- 29453347
TI  - Reversing Coffee-Ring Effect by Laser-Induced Differential Evaporation.
AB  - The coffee-ring effect, ubiquitously present in the drying process of aqueous
      droplets, impedes the performance of a myriad of applications involving
      precipitation of particle suspensions in evaporating liquids on solid surfaces,
      such as liquid biopsy combinational analysis, microarray fabrication, and ink-jet
      printing, to name a few. We invented the methodology of laser-induced
      differential evaporation to remove the coffee-ring effect. Without any additives
      to the liquid or any morphology modifications of the solid surface the liquid
      rests on, we have eliminated the coffee-ring effect by engineering the liquid
      evaporation profile with a CO2 laser irradiating the apex of the droplets. The
      method of laser-induced differential evaporation transitions particle deposition
      patterns from coffee-ring patterns to central-peak patterns, bringing all
      particles (e.g. fluorescent double strand DNAs) in the droplet to a designated
      area of 100 MUm diameter without leaving any stains outside. The technique also
      moves the drying process from the constant contact radius (CCR) mode to the
      constant contact angle (CCA) mode. Physical mechanisms of this method were
      experimentally studied by internal flow tracking and surface evaporation flux
      mapping, and theoretically investigated by development of an analytical model.

PMID- 29453348
TI  - ABCG2 contributes to the development of gout and hyperuricemia in a genome-wide
      association study.
AB  - Although many genome-wide association studies (GWASs) of hyperuricemia or gout
      have been reported, the related genetic factors and the mechanisms from
      hyperuricemia to gouty attack remain unclear. This study aimed to identify
      genetic factors and pathogenesis of gout from hyperuricemia by genome-wide
      association study (GWAS). 747 gout patients, 747 hyperuricemia and 2071 age
      matched controls were recruited and analyzed with Affymetrix 650 K chip to find
      the related genetic variants. The functions of the related genes were
      investigated in an endothelial cell (EC) with urate crystal stimulation. The GWAS
      results showed 36 SNPs to be strongly associated with gout compared to controls
      (all p-values < 10-7). Whereas the rs2231142 in ABCG2 gene had significant
      associations between gout and controls, between gout and hyperuricemia, and
      between hyperuricemia and controls (all p-values < 10-7), and the ORs were 4.34,
      3.37 and 2.15 (all p-values < 0.001) after adjustment of potential confounders,
      respectively. The cell model showed significantly higher IL-8 release from EC
      combined with ABCG2 knockdown. We concluded that ABCG2 gene contributed to
      hyperuricemia but also gout, and that it was involved in the inflammation
      dysregulation via augmented IL-8 release in EC.

PMID- 29453350
TI  - Navigating the unfolding open data landscape in ecology and evolution.
AB  - Open access to data is revolutionizing the sciences. To allow ecologists and
      evolutionary biologists to confidently find and use the existing data, we provide
      an overview of the landscape of online data infrastructures, and highlight the
      key points to consider when using open data. We introduce an online collaborative
      platform to keep a community-driven, updated list of the best sources that enable
      search for data in one interface. In doing so, our aim is to lower the barrier to
      accessing open data, and encourage its use by researchers hoping to increase the
      scope, reliability and value of their findings.

PMID- 29453349
TI  - Ultrasound and shock-wave stimulation to promote axonal regeneration following
      nerve surgery: a systematic review and meta-analysis of preclinical studies.
AB  - Limited regeneration after nerve injury often leads to delayed or incomplete
      reinnervation and consequently insufficient muscle function. Following nerve
      surgery, application of low-intensity ultrasound or extracorporeal shock waves
      may promote nerve regeneration and improve functional outcomes. Because currently
      clinical data is unavailable, we performed a meta-analysis following the PRISMA
      guidelines to investigate the therapeutic effect of ultrasound and shock wave
      therapies on motor nerve regeneration. Ten ultrasound-studies (N = 445 rats) and
      three shock-wave studies (N = 110 rats) were identified from multiple databases.
      We calculated the difference in means or standardized mean difference with 95%
      confidence intervals for motor function, nerve conduction velocity and
      histomorphological parameters of treated versus sham or non-treated animals.
      Ultrasound treatment showed significantly faster nerve conduction, increased
      axonal regeneration with thicker myelin and improved motor function on sciatic
      functional index scale (week two: DM[95%CI]: 19,03[13,2 to 25,6], 71 animals;
      week four: 7,4[5,4 to 9,5], 47 animals). Shock wave induced recovery improvements
      were temporarily significant. In conclusion, there is significant evidence for
      low-intensity ultrasound but not for extracorporeal shock wave treatment to
      improve nerve regeneration. Prospective clinical trials should therefore
      investigate available FDA-approved ultrasound devices as adjunct postoperative
      treatment following nerve surgery.

PMID- 29453351
TI  - Resistance is ... complex.

PMID- 29453352
TI  - Redefining ecosystem multifunctionality.
AB  - Recent years have seen a surge of interest in ecosystem multifunctionality, a
      concept that has developed in the largely separate fields of biodiversity
      ecosystem function and land management research. Here we discuss the merit of the
      multifunctionality concept, the advances it has delivered, the challenges it
      faces and solutions to these challenges. This involves the redefinition of
      multifunctionality as a property that exists at two levels: ecosystem function
      multifunctionality and ecosystem service multifunctionality. The framework
      presented provides a road map for the development of multifunctionality measures
      that are robust, quantifiable and relevant to both fundamental ecological science
      and ecosystem management.

PMID- 29453353
TI  - Author Correction: Uplift of the central transantarctic mountains.
AB  - The original version of this Article incorrectly referenced the Figures in the
      Supplementary Information. References in the main Article to Supplementary Figure
      7 through to Supplementary Figure 20 were previously incorrectly cited as
      Supplementary Figure 5 through to Supplementary Figure 18, respectively. This has
      now been corrected in both the PDF and HTML versions of the Article.

PMID- 29453354
TI  - Physical basis of amyloid fibril polymorphism.
AB  - Polymorphism is a key feature of amyloid fibril structures but it remains
      challenging to explain these variations for a particular sample. Here, we report
      electron cryomicroscopy-based reconstructions from different fibril morphologies
      formed by a peptide fragment from an amyloidogenic immunoglobulin light chain.
      The observed fibril morphologies vary in the number and cross-sectional
      arrangement of a structurally conserved building block. A comparison with the
      theoretically possible constellations reveals the experimentally observed
      spectrum of fibril morphologies to be governed by opposing sets of forces that
      primarily arise from the beta-sheet twist, as well as peptide-peptide
      interactions within the fibril cross-section. Our results provide a framework for
      rationalizing and predicting the structure and polymorphism of cross-beta
      fibrils, and suggest that a small number of physical parameters control the
      observed fibril architectures.

PMID- 29453356
TI  - Coastal polynyas: Winter oases for subadult southern elephant seals in East
      Antarctica.
AB  - Antarctic coastal polynyas are regions of persistent open water and are thought
      to be key bio-physical features within the sea-ice zone. However, their use by
      the upper trophic levels of ecosystems remains unclear. A unique bio-physical
      dataset recorded by southern elephant seals reveals that East Antarctic polynyas
      are a key winter foraging habitat for male seals. During their post-moult trips
      from Isles Kerguelen to the Antarctic continental shelf, a total of 18 out of 23
      seals visited 9 different polynyas, spending on average 25 +/- 20% (up to 75%) of
      their total trip time inside polynyas. Changes in seal foraging and diving
      behaviours are observed inside polynyas as compared to outside polynyas. Two
      polynya usages by seals are observed for the inactive and active polynya phases,
      pointing to different seasonal peaks in prey abundance. During the active polynya
      phase, we link seal foraging behaviour to changes in the physical stability of
      the water-column, which likely impact the seasonal biological dynamics within
      polynyas.

PMID- 29453355
TI  - Co-expression network analysis and cis-regulatory element enrichment determine
      putative functions and regulatory mechanisms of grapevine ATL E3 ubiquitin
      ligases.
AB  - Arabidopsis thaliana Toxicos en Levadura (ATL) proteins are a subclass of the
      RING-H2 zinc finger binding E3 ubiquitin ligases. The grapevine (Vitis vinifera)
      ATL family was recently characterized, revealing 96 members that are likely to be
      involved in several physiological processes through protein ubiquitination.
      However, the final targets and biological functions of most ATL E3 ligases are
      still unknown. We analyzed the co-expression networks among grapevine ATL genes
      across a set of transcriptomic data related to defense and abiotic stress,
      combined with a condition-independent dataset. This revealed strong correlations
      between ATL proteins and diverse signal transduction components and
      transcriptional regulators, in particular those involved in immunity. An
      enrichment analysis of cis-regulatory elements in ATL gene promoters and related
      co-expressed genes highlighted the importance of hormones in the regulation of
      ATL gene expression. Our work identified several ATL proteins as candidates for
      further studies aiming to decipher specific grapevine resistance mechanisms
      activated in response to pathogens.

PMID- 29453357
TI  - The effect of fidget spinners on fine motor control.
AB  - Fidgeting, defined as the generation of small movements through nervousness or
      impatience, is one of cardinal characteristic of ADHD. While fidgeting is, by
      definition, a motor experience still nothing is known about the effects of
      fidgeting on motor control. Some forms of fidgeting involve also the manipulation
      of external objects which, through repetition, may become automatic and second
      nature. Both repetition and practice are important for the acquisition of motor
      skills and, therefore, it is plausible that the repetitive manipulation of
      objects may influence motor control and performance. As such, fidget spinners, by
      being diffuse and prone to repetitive usage, may represent interesting tool for
      improving motor control. In this study we examine the effect of fidget spinners
      on fine motor control, evaluated by a spiral-tracing task. We show that the use
      of fidget spinner indeed seems to have a favorable effect on fine motor control,
      at least in the short term, although this effect does not seem to be in any way
      inherent to fidget spinners themselves as much as to object manipulation in
      general. However, due to their widespread usage, fidget spinner may have the
      advantage of being an enjoyable means for improving fine motor control.

PMID- 29453358
TI  - Georeferenced soil provenancing with digital signatures.
AB  - The provenance or origin of a soil sample is of interest in soil forensics,
      archaeology, and biosecurity. In all of these fields, highly specialized and
      often expensive analysis is usually combined with expert interpretation to
      estimate sample origin. In this proof of concept study we apply rapid and non
      destructive spectral analysis to the question of direct soil provenancing. This
      approach is based on one of the underlying tenets of soil science - that soil
      pedogenesis is spatially unique, and thus digital spectral signatures of soil can
      be related directly, rather than via individual soil properties, to a
      georeferenced location. We examine three different multivariate regression
      techniques to predict GPS coordinates in two nested datasets. With a minimum of
      data processing, we show that in most instances Eastings and Northings can be
      predicted to within 20% of the range of each within the dataset using the
      spectral signatures produced via portable x-ray fluorescence. We also generate 50
      and 95% confidence intervals of prediction and express these as a range of GPS
      coordinates. This approach has promise for future application in soil and
      environmental provenancing.

PMID- 29453359
TI  - Rational Construction of Uniform CoNi-Based Core-Shell Microspheres with Tunable
      Electromagnetic Wave Absorption Properties.
AB  - Core-shell particles with integration of ferromagnetic core and dielectric shell
      are attracting extensive attention for promising microwave absorption
      applications. In this work, CoNi microspheres with conical bulges were
      synthesized by a simple and scalable liquid-phase reduction method. Subsequent
      coating of dielectric materials was conducted to acquire core-shell structured
      CoNi@TiO2 composite particles, in which the thickness of TiO2 is about 40 nm. The
      coating of TiO2 enables the absorption band of CoNi to effectively shift from Ku
      to S band, and endows CoNi@TiO2 microspheres with outstanding electromagnetic
      wave absorption performance along with a maximum reflection loss of 76.6 dB at
      3.3 GHz, much better than that of bare CoNi microspheres (54.4 dB at 17.8 GHz).
      The enhanced EMA performance is attributed to the unique core-shell structures,
      which can induce dipole polarization and interfacial polarization, and tune the
      dielectric properties to achieve good impedance matching. Impressively, TiO2
      coating endows the composites with better microwave absorption capability than
      CoNi@SiO2 microspheres. Compared with SiO2, TiO2 dielectric shells could protect
      CoNi microspheres from merger and agglomeration during annealed. These results
      indicate that CoNi@TiO2 core-shell microspheres can serve as high-performance
      absorbers for electromagnetic wave absorbing application.

PMID- 29453360
TI  - Role of intestinal trefoil factor in protecting intestinal epithelial cells from
      burn-induced injury.
AB  - Although intestinal trefoil factor (ITF) can alleviate the burn-induced
      intestinal mucosa injury, the underlying mechanisms remains elusive. In this
      study, we investigated if ITF alters glutamine transport on the brush border
      membrane vesicles (BBMVs) of the intestines in Sprague-Dawley rats inflicted with
      30% TBSA and the underlying mechanisms. We found that ITF significantly
      stimulated intestinal glutamine transport in burned rats. Mechanistically, ITF
      enhanced autophagy, reduces endoplasmic reticulum stress (ERS), and alleviates
      the impaired PDI, ASCT2, and B0AT1 in IECs and BBMVs after burn injury likely
      through AMPK activation. Therefore, ITF may protect intestinal epithelial cells
      from burn-induced injury through improving glutamine transport by alleviating
      ERS.

PMID- 29453361
TI  - Heterogeneity and mutation in KRAS and associated oncogenes: evaluating the
      potential for the evolution of resistance to targeting of KRAS G12C.
AB  - Activating mutations in RAS genes are associated with approximately 20% of all
      human cancers. New targeted therapies show preclinical promise in inhibiting the
      KRAS G12C variant. However, concerns exist regarding the effectiveness of such
      therapies in vivo given the possibilities of existing intratumor heterogeneity or
      de novo mutation leading to treatment resistance. We performed deep sequencing of
      27 KRAS G12-positive lung tumors to determine the prevalence of other oncogenic
      mutations within KRAS or within commonly mutated downstream genes that could
      confer resistance at the time of treatment. We also passaged patient-derived
      xenografts to assess the potential for novel KRAS mutation to arise during
      subsequent tumor evolution. Furthermore, we estimate the de novo mutation rate in
      KRAS position 12 and in genes downstream of KRAS. Finally, we present an approach
      for estimation of the selection intensity for these point mutations that explains
      their high prevalence in tumors. We find no evidence of heterogeneity that may
      compromise KRAS G12C targeted therapy within sequenced lung tumors or passaged
      xenografts. We find that mutations that confer resistance are even less likely to
      occur downstream of KRAS than to occur within KRAS. Our approach predicts that
      BRAF V600E would provide the highest fitness advantage for de novo-resistant
      subclones. Overall, our findings suggest that resistance to targeted therapy of
      KRAS G12C-positive tumors is unlikely to be present at the time of treatment and,
      among the de novo mutations likely to confer resistance, mutations in BRAF, a
      gene with targeted inhibitors presently available, result in subclones with the
      highest fitness advantage.

PMID- 29453362
TI  - Long-term bladder and bowel management after spinal cord injury: a 20-year
      longitudinal study.
AB  - STUDY DESIGN: Prospective observational. AIM: The aim of this study was to
      analyse changes in bladder and bowel management methods in persons with long
      standing spinal cord injury (SCI). SETTING: Two spinal centres in UK. METHOD:
      Data were collected through interviews and examinations between 1990 and 2010 in
      a sample of persons injured more than 20 years prior to 1990. RESULTS: For the 85
      participants who completed the 2010 follow-up, the mean age was 67.7 years and
      the mean duration of injury was 46.3 years, 80% were male, 37.7% had tetraplegia
      AIS grade A, B, or C, 44.7% paraplegia AIS A, B, or C, and 17.6% an AIS D grade
      regardless of level. In all, 50.6% reported having changed their bladder method,
      63.1% their bowel method, and 40.5% both methods since they enroled in the study.
      The reasons for change were a combination of medical and practical. In men,
      condom drainage remained the most frequent bladder method, and in women,
      suprapubic catheter replaced straining/expressing as the most frequent method.
      The use of condom drainage and straining/expressing bladder methods decreased,
      whereas the use of suprapubic and intermittent catheters increased. Manual
      evacuation remained the most frequent bowel management method. The percentage of
      participants on spontaneous/voluntary bowel emptying, straining and medications
      alone decreased, whereas the use of colostomy and transanal irrigation increased
      over time. CONCLUSIONS: More than half the sample, all living with SCI for more
      than 40 years, required change in their bladder and bowel management methods, for
      either medical or practical reasons. Regular follow-ups ensure adequate change of
      method if/when needed.

PMID- 29453363
TI  - Guiding of laser pulses in plasma waveguides created by linearly-polarized
      femtosecond laser pulses.
AB  - We experimentally demonstrate that plasma waveguides produced with ultra-short
      laser pulses (sub-picosecond) in gas jets are capable of guiding high intensity
      laser pulses. This scheme has the unique ability of guiding a high-intensity
      laser pulse in a plasma waveguide created by the same laser system in the very
      simple and stable experimental setup. A hot plasma column was created by a
      femtosecond class laser that expands into an on-axis parabolic low density
      profile suitable to act as a waveguide for high intensity laser beams. We have
      successfully guided ~1015 W cm-2 laser pulses in a 8 mm long hydrogen plasma
      waveguide with a 35% guiding efficiency.

PMID- 29453365
TI  - High fidelity heralded single-photon source using cavity quantum electrodynamics.
AB  - Demands for single-photon sources are ubiquitous in quantum information
      processing as well as in quantum metrology. In many protocols for producing
      single photons, a cavity-emitter configuration is used. In such cavity quantum
      electrodynamical systems, the cavity can enforce a well-defined output mode for
      the photon and enhance its collection efficiency, while the emitter is
      indispensable for single photon emission. Here we show the two cavity-one two
      level emitter configuration can be used to produce exclusively photon pairs, with
      each photon in a separate mode. Conditioning on detecting a photon in one of the
      modes, one heralds with high fidelity a single photon in the other mode.
      Counterintuitively, upon decreasing the coupling of the emitter to one of the
      modes, the heralding fidelity can further increase.

PMID- 29453367
TI  - Quantitative Analysis of Charge Distribution in Bi-Emissive layer White Organic
      Light-Emitting Diodes with Two Fluorescent Dopants.
AB  - This work seeks to establish a quantitative method which can estimate the holes
      and electrons ratio in the emission zones. We fabricated multilayered white
      organic light-emitting diodes (WOLEDs) with the device structure of ITO/NPB(80
      nm)/MADN:BUBD-1(7%)(20 nm)/MADN:DCJTB(0.3%)(20 nm)/TPBi(X nm)/LiF(2 nm)/Al as a
      case study on the charge recombination distribution in the emissive layer. The
      result shows a trend in the charge recombination ratio depending on the electron
      transport layer thickness. We obtained an empirical relationship between electron
      transport layer thicknesses and emission ratio in EML. In addition, the
      electroluminescent spectra were analyzed by fitting a Gaussian distribution for
      the two emissive layers to calculate the intensity ratio of the energy
      transitions. The arrival time of hole and electrons from each electrode was
      determined using the thickness and mobility of TPBi as electron transport layer.
      From these initial results, we derived an empirical mechanism to meet with a
      linear relationship that can allow us to design custom- made WOLEDs.

PMID- 29453364
TI  - Biogeographical Differences in the Influence of Maternal Microbial Sources on the
      Early Successional Development of the Bovine Neonatal Gastrointestinal tract.
AB  - The impact of maternal microbial influences on the early choreography of the
      neonatal calf microbiome were investigated. Luminal content and mucosal scraping
      samples were collected from ten locations in the calf gastrointestinal tract
      (GIT) over the first 21 days of life, along with postpartum maternal colostrum,
      udder skin, and vaginal scrapings. Microbiota were found to vary by anatomical
      location, between the lumen and mucosa at each GIT location, and differentially
      enriched for maternal vaginal, skin, and colostral microbiota. Most calf sample
      sites exhibited a gradual increase in alpha-diversity over the 21 days beginning
      the first few days after birth. The relative abundance of Firmicutes was greater
      in the proximal GIT, while Bacteroidetes were greater in the distal GIT.
      Proteobacteria exhibited greater relative abundances in mucosal scrapings
      relative to luminal content. Forty-six percent of calf luminal microbes and 41%
      of mucosal microbes were observed in at-least one maternal source, with the
      majority being shared with microbes on the skin of the udder. The vaginal
      microbiota were found to harbor and uniquely share many common and well-described
      fibrolytic rumen bacteria, as well as methanogenic archaea, potentially
      indicating a role for the vagina in populating the developing rumen and reticulum
      with microbes important to the nutrition of the adult animal.

PMID- 29453366
TI  - Time-dependent Enhanced Corrosion of Ti6Al4V in the Presence of H2O2 and Albumin.
AB  - There is increasing concern regarding the biological consequences of metal
      release from implants. However, the mechanisms underpinning implant surface
      degradation, especially in the absence of wear, are often poorly understood. Here
      the synergistic effect of albumin and H2O2 on corrosion of Ti6Al4V in
      physiological saline is studied with electrochemical methods. It is found that
      albumin induces a time-dependent dissolution of Ti6Al4V in the presence of H2O2
      in physiology saline. Potentiostatic polarisation measurements show that albumin
      supresses dissolution in the presence of H2O2 at short times (<24 h) but over
      longer time periods (120 h) it significantly accelerates corrosion, which is
      attributed to albumin-catalysed dissolution of the corrosion product layer
      resulting in formation of a thinner oxide film. Dissolution of Ti6Al4V in the
      presence of albumin and H2O2 in physiological saline is also found to be
      dependent on potential: the titanium ion release rate is found to be higher (0.57
      ug/cm2) at a lower potential (90 mV), where the oxide capacitance and resistance
      inferred from Electrochemical Impedance Spectroscopy also suggests a less
      resistant oxide film. The study highlights the importance of using more realistic
      solutions, and considering behaviour over longer time periods when testing
      corrosion resistance of metallic biomaterials.

PMID- 29453368
TI  - Effects of timber harvesting on the genetic potential for carbon and nitrogen
      cycling in five North American forest ecozones.
AB  - Forest ecosystems are critical to global biogeochemical cycles but under pressure
      from harvesting and climate change. We investigated the effects of organic matter
      (OM) removal during forest harvesting on the genetic potential of soil
      communities for biomass decomposition and nitrogen cycling in five ecozones
      across North America. We analyzed 107 samples, representing four treatments with
      varied levels of OM removal, at Long-Term Soil Productivity Study sites. Samples
      were collected more than ten years after harvesting and replanting and were
      analyzed via shotgun metagenomics. High-quality short reads totaling 1.2 Tbp were
      compared to the Carbohydrate Active Enzyme (CAZy) database and a custom database
      of nitrogen cycle genes. Gene profile variation was mostly explained by ecozone
      and soil layer. Eleven CAZy and nine nitrogen cycle gene families were associated
      with particular soil layers across all ecozones. Treatment effects on gene
      profiles were mainly due to harvesting, and only rarely to the extent of OM
      removal. Harvesting generally decreased the relative abundance of CAZy genes
      while increasing that of nitrogen cycle genes, although these effects varied
      among ecozones. Our results suggest that ecozone-specific nutrient availability
      modulates the sensitivity of the carbon and nitrogen cycles to harvesting with
      possible consequences for long-term forest sustainability.

PMID- 29453369
TI  - Intratesticular injection followed by electroporation allows gene transfer in
      caprine spermatogenic cells.
AB  - The production of transgenic livestock is constrained due to the limited success
      of currently available methods for transgenesis. Testis mediated gene transfer
      (TMGT) is an emerging method that shows a high success rate in generating
      transgenic mice. In this study, we report a newly developed protocol for
      electroporation-aided TMGT to produce a transgenic goat. The injectable volume
      and concentration of the transgene were first standardized, and then
      electroporation conditions were optimized in vitro. In vivo experiments were
      performed by injecting a transgenic construct (pIRES2-EGFP; enhanced green
      fluorescent protein) into the testicular interstitium followed by
      electroporation. Immunohistochemistry, quantitative real-time PCR (qPCR) and
      western blotting analyses confirmed the successful transfer of the transgene into
      seminiferous tubules and testicular cells. Furthermore, chromosomal integration
      of the transgene and its expression in sperm were evaluated d60 and d120 post
      electroporation. Our protocol neither altered the seminal characteristics nor the
      fertilization capacity of the sperm cells. In vitro fertilization using
      transgenic sperm generated fluorescent embryos. Finally, natural mating of a pre
      founder buck produced a transgenic baby goat. The present study demonstrates the
      first successful report of an electroporation-aided TMGT method for gene transfer
      in goats.

PMID- 29453370
TI  - A multitarget approach to drug discovery inhibiting Mycobacterium tuberculosis
      PyrG and PanK.
AB  - Mycobacterium tuberculosis, the etiological agent of the infectious disease
      tuberculosis, kills approximately 1.5 million people annually, while the spread
      of multidrug-resistant strains is of great global concern. Thus, continuous
      efforts to identify new antitubercular drugs as well as novel targets are
      crucial. Recently, two prodrugs activated by the monooxygenase EthA, 7947882 and
      7904688, which target the CTP synthetase PyrG, were identified and characterized.
      In this work, microbiological, biochemical, and in silico methodologies were used
      to demonstrate that both prodrugs possess a second target, the pantothenate
      kinase PanK. This enzyme is involved in coenzyme A biosynthesis, an essential
      pathway for M. tuberculosis growth. Moreover, compound 11426026, the active
      metabolite of 7947882, was demonstrated to directly inhibit PanK, as well. In an
      independent screen of a compound library against PyrG, two additional inhibitors
      were also found to be active against PanK. In conclusion, these direct PyrG and
      PanK inhibitors can be considered as leads for multitarget antitubercular drugs
      and these two enzymes could be employed as a "double-tool" in order to find
      additional hit compounds.

PMID- 29453371
TI  - Plasmonic Spherical Heterodimers: Reversal of Optical Binding Force Based on the
      Forced Breaking of Symmetry.
AB  - The stimulating connection between the reversal of near-field plasmonic binding
      force and the role of symmetry-breaking has not been investigated comprehensively
      in the literature. In this work, the symmetry of spherical plasmonic heterodimer
      setup is broken forcefully by shining the light from a specific side of the set
      up instead of impinging it from the top. We demonstrate that for the forced
      symmetry-broken spherical heterodimer-configurations: reversal of lateral and
      longitudinal near-field binding force follow completely distinct mechanisms.
      Interestingly, the reversal of longitudinal binding force can be easily
      controlled either by changing the direction of light propagation or by varying
      their relative orientation. This simple process of controlling binding force may
      open a novel generic way of optical manipulation even with the heterodimers of
      other shapes. Though it is commonly believed that the reversal of near-field
      plasmonic binding force should naturally occur for the presence of bonding and
      anti-bonding modes or at least for the Fano resonance (and plasmonic forces
      mostly arise from the surface force), our study based on Lorentz-force dynamics
      suggests notably opposite proposals for the aforementioned cases. Observations in
      this article can be very useful for improved sensors, particle clustering and
      aggregation.

PMID- 29453372
TI  - Enzyme mediated nanofibrillation of cellulose by the synergistic actions of an
      endoglucanase, lytic polysaccharide monooxygenase (LPMO) and xylanase.
AB  - Physiochemical methods have generally been used to "open-up" biomass
      substrates/pulps and have been the main method used to fibrillate cellulose.
      However, recent work has shown that canonical cellulase enzymes such as
      endoglucanases, in combination with "amorphogenesis inducing" proteins such as
      lytic polysaccharide monooxygenases (LPMO), swollenin and hemicellulases, are
      able to increase cellulose accessibility. In the work reported here different
      combinations of endoglucanase, LPMO and xylanase were applied to Kraft pulps to
      assess their potential to induce fibrillation at low enzyme loading over a short
      time period. Although gross fiber properties (fiber length, width and morphology)
      were relatively unchanged, over a short period of time, the intrinsic
      physicochemical characteristics of the pulp fibers (e.g. cellulose
      accessibility/DP/crystallinity/charge) were positively enhanced by the
      synergistic cooperation of the enzymes. LPMO addition resulted in the oxidative
      cleavage of the pulps, increasing the negative charge (~100 mmol kg-1) on the
      cellulose fibers. This improved cellulose nanofibrilliation while stabilizing the
      nanofibril suspension (zeta potential zeta = ~60 mV), without sacrificing
      nanocellulose thermostability. The combination of endoglucanase, LPMO and
      xylanases was shown to facilitate nanofibrillation, potentially reducing the need
      for mechanical refining while resulting in a pulp with a more uniform nanofibril
      composition.

PMID- 29453373
TI  - Dormancy release and germination of Taxus yunnanensis seeds during wet sand
      storage.
AB  - Dormancy is an innate constraint on germination that occurs across all life
      forms. In this study, we investigated the seed dormancy release and germination
      characters of Taxus yunnanensis by exploring the seed morphology, permeability,
      germination inhibitors, endogenous hormones, and embryo germination in vitro
      during wet sand storage. Our results showed that seeds and embryos grew to a
      critical size to germination and permeability increased with the extension of
      storage. Seed coat and kernel methanol extracts reduced Brassica campestris seed
      vigor index. The in vitro embryo germination rate increased by 12.20% after
      storage for 30-360 d, whereas seed germination occurred after 450 d. Gibberellic
      acid and zeatin riboside contents were relatively stable, whereas abscisic acid
      (ABA) content decreased; indole acetic acid (IAA) content and the IAA/ABA ratio
      showed increasing trends. These results indicate that ABA is the key inhibitor of
      germination in Taxus. The chemical(s) in seed coat and kernel cause the
      inhibition of seed germination. Taken together, Taxus seeds have
      morphophysiological dormancy, in which the embryos can continue to grow and
      hormone imbalance inhibits further development and germination. Further, seed
      dormancy is active even during the middle of storage and shows "double peaks"
      during the entire dormancy process.

PMID- 29453374
TI  - Cardiovascular and renal protective role of angiotensin blockade in hypertension
      with advanced CKD: a subgroup analysis of ATTEMPT-CVD randomized trial.
AB  - The ATTEMPT-CVD study was prospective randomized active-controlled trial and the
      main findings had been reported. According to baseline GFR and albuminuria
      categories, we divided the patients of the ATTEMPT-CVD study into 2 subgroups:
      (Group 1) the patients with at least one of eGFR of <45 ml/min per 1.73 m2 and
      UACR of >=300 mg/g creatinine, defined as G3b and/or A3; (Group 2) the patients
      except for Group 1, defined as the other patients. In patients with G3b and/or
      A3, the incidence of cardiovascular events was significantly less in ARB group
      than in non-ARB group (11 vs 22, respectively) (HR = 0.465: 95%CI = 0.224-0.965;
      P = 0.040). UACR was significantly less in ARB group than in non-ARB group during
      follow-up period in patients with G3b and/or A3 (P = 0.0003), while eGFR, plasma
      BNP levels, and blood pressure were comparable between ARB and non-ARB groups.
      Allocation to ARB therapy was a significant independent prognostic factor for
      cardiovascular events in patients with G3b and/or A3 (P = 0.0268). On the other
      hand, in the other patients, the occurrence of cardiovascular events was
      comparable between ARB and non-ARB groups. In patients with advanced CKD, ARB
      based therapy may confer greater benefit in prevention of cardiovascular events
      than non-ARB therapy.

PMID- 29453375
TI  - Self-supporting Co3O4/Graphene Hybrid Films as Binder-free Anode Materials for
      Lithium Ion Batteries.
AB  - A self-supporting Co3O4/graphene hybrid film has been constructed via vacuum
      filtration of Co(OH)2 nanosheet and graphene, followed by a two-step thermal
      treatment. Within the hybrid film, Co3O4 nanoparticles with size of 40~60 nm
      uniformly in-situ grew on the surface of graphene, forming a novel porous and
      interleaved structure with strong interactions between Co3O4 nanoparticles and
      graphene. Such fascinating microstructures can greatly facilitate interfacial
      electron transportation and accommodate the volume changes upon Li ions insertion
      and extraction. Consequently, the binder-less hybrid film demonstrated extremely
      high reversible capacity (1287.7 mAh g-1 at 0.2 A g-1), excellent cycling
      stability and rate capability (1110 and 800 mAh g-1 at 0.5 and 1.0 A g-1,
      respectively).

PMID- 29453376
TI  - High quality self-separated GaN crystal grown on a novel nanoporous template by
      HVPE.
AB  - In this study, a novel nanoporous template was obtained by a two-step etching
      process from MOCVD-GaN/Al2O3 (MGA) with electrochemical etching sequentially
      followed by chemical wet etching. The twice-etched MOCVD-GaN/Al2O3 (TEMGA)
      templates were utilized to grow GaN crystals by hydride vapor phase epitaxy
      (HVPE) method. The GaN crystals were separated spontaneously from the TEMGA
      template with the assistance of voids formed by the etched nanopores. Several
      techniques were utilized to characterize the quality of the free-standing GaN
      crystals obtained from the TEMGA template. Results showed that the quality of the
      as-obtained GaN crystals was improved obviously compared with those grown on the
      MGA. This convenient technique can be applied to grow high-quality free-standing
      GaN crystals.

PMID- 29453377
TI  - Optimized peptide based inhibitors targeting the dihydrofolate reductase pathway
      in cancer.
AB  - We report the first peptide based hDHFR inhibitors designed on the basis of
      structural analysis of dihydrofolate reductase (DHFR). A set of peptides were
      rationally designed and synthesized using solid phase peptide synthesis and
      characterized using nuclear magnetic resonance and enzyme immunoassays. The best
      candidate among them, a tetrapeptide, was chosen based on molecular mechanics
      calculations and evaluated in human lung adenocarcinoma cell line A549. It showed
      a significant reduction of cell proliferation and an IC50 of 82 uM was obtained.
      The interaction of the peptide with DHFR was supported by isothermal calorimetric
      experiments revealing a dissociation constant Kd of 0.7 uM and DeltaG of -34 +/-
      1 kJ mol-1. Conjugation with carboxylated polystyrene nanoparticles improved
      further its growth inhibitory effects. Taken together, this opens up new avenues
      to design, develop and deliver biocompatible peptide based anti-cancer agents.

PMID- 29453378
TI  - Phenotypic plasticity vs. local adaptation in quantitative traits differences of
      Stipa grandis in semi-arid steppe, China.
AB  - Whether plants are able to adapt to environmental changes depends on their
      genetic characteristics and phenotypic plastic responses. We investigated the
      phenotypic responses of 7 populations of an important dominant species in semi
      arid steppe of China - Stipa grandis, and then distinguished which adaptive
      mechanism(s), phenotypic plasticity or local adaptation, was/were involved in
      this species to adapt to environmental changes. (1) All traits were significantly
      influenced by the interaction of population and growth condition and by
      population in each condition, and inter-population variability (CVinter) was
      larger in the field than in the common garden for 8/9 traits, indicating that
      both phenotypic plasticity and genetic differentiation controlled the phenotypic
      differences of S. grandis. (2) From a functional standpoint, the significant
      relationships between the values of traits in the common garden and the
      environmental variables in their original habitats couldn't support local habitat
      adaptation of these traits. (3) Low CVintra, low quantitative differentiation
      among populations (Q ST ), and low plasticity shown in the western populations
      indicated the very low adaptive potential of S. grandis to environmental changes.
      (4) From the original habitats to the common garden which is far away from S.
      grandis distribution region, positive phenotypic responses were found in several
      populations, indicating that some original habitats have become unfavorable for
      S. grandis.

PMID- 29453379
TI  - Comment on "Systematic review and meta-analysis by Dube et al."

PMID- 29453380
TI  - The intricacies of the Mediterranean diet in NAFLD.

PMID- 29453381
TI  - Choledocholithiasis in Roux-en-Y gastric bypass patients.

PMID- 29453382
TI  - Rectal Exam: Yes, it can and should be done in a busy practice!

PMID- 29453383
TI  - Hyperbaric oxygen therapy is well tolerated and effective for ulcerative colitis
      patients hospitalized for moderate-severe flares: a phase 2A pilot multi-center,
      randomized, double-blind, sham-controlled trial.
AB  - BACKGROUND: Hyperbaric oxygen therapy (HBOT) markedly increases tissue oxygen
      delivery. Case series suggest it may have a potential therapeutic benefit in
      ulcerative colitis (UC). We investigated the therapeutic potential of HBOT as an
      adjunct to steroids for UC flares requiring hospitalization. METHODS: The study
      was terminated early due to poor recruitment with 18 of the planned 70 patients
      enrolled. UC patients hospitalized for moderate-severe flares (Mayo score >=6,
      endoscopic sub-score >=2) were block randomized to steroids + daily HBOT (n = 10)
      or steroids + daily sham hyperbaric air (n = 8). Patients were blinded to study
      assignment, and assessments were performed by a blinded gastroenterologist.
      Primary outcome was the clinical remission rate at study day 5 (partial Mayo
      score <=2 with no sub-score >1). Key secondary outcomes were: clinical response
      (reduction in partial Mayo score >=2, rectal bleeding sub-score of 0-1) and
      progression to second-line therapy (colectomy or biologic therapy) during the
      hospitalization. RESULTS: A significantly higher proportion of HBOT-treated
      patients achieved clinical remission at study day 5 and 10 (50 vs. 0%, p = 0.04).
      HBOT-treated patients less often required progression to second-line therapy
      during the hospitalization (10 vs. 63%, p = 0.04). The proportion requiring in
      hospital colectomy specifically as second-line therapy for medically refractory
      UC was lower in the HBOT group compared to sham (0 vs. 38%, p = 0.07). There were
      no serious adverse events. CONCLUSION: In this small, proof-of-concept, phase 2A
      trial, the use of HBOT as an adjunctive therapy to steroids for UC patients
      hospitalized for moderate-severe flares resulted in higher rates of clinical
      remission, and a reduction in rates of progression to second-line therapy during
      the hospitalization. Larger well-powered trials are needed, however, to provided
      definitive evidence of therapeutic benefit.

PMID- 29453384
TI  - Longitudinal impact of IBS-type symptoms on disease activity, healthcare
      utilization, psychological health, and quality of life in inflammatory bowel
      disease.
AB  - OBJECTIVES: The impact of irritable bowel syndrome (IBS)-type symptoms on the
      natural history of inflammatory bowel disease (IBD) is uncertain. We aimed to
      address this in a longitudinal study of secondary care patients. METHODS:
      Longitudinal disease activity was defined by disease flare, escalation of medical
      therapy, hospitalization, or intestinal resection. The number of investigations
      performed and clinics attended determined healthcare utilization. Psychological
      well-being and quality of life were assessed using validated questionnaires.
      These outcomes were compared over a minimum period of 2 years between patients
      reporting IBS-type symptoms and patients with quiescent disease, occult
      inflammation, and active disease at baseline. RESULTS: In 360 IBD patients, there
      were no differences in longitudinal disease activity between patients with IBS
      type symptoms and patients with quiescent disease or occult inflammation. Disease
      flare and escalation of medical therapy was more common in patients with active
      disease than in patients with IBS-type symptoms (hazard ratio (HR) = 3.16; 95%
      confidence interval (CI) 1.93-5.19 and HR = 3.24; 95% CI 1.98-5.31,
      respectively). A greater number of investigations were performed in patients with
      IBS-type symptoms than quiescent disease (P = 0.008), but not compared with
      patients with occult inflammation or active disease. Anxiety, depression, and
      somatization scores at follow up were higher, and quality-of-life scores lower,
      in patients with IBS-type symptoms when compared with patients with quiescent
      disease, but were similar to patients with active disease. CONCLUSIONS: IBS-type
      symptoms in IBD were associated with increased healthcare utilization,
      psychological comorbidity, reduced quality of life, but not adverse disease
      activity outcomes during extended follow-up.

PMID- 29453385
TI  - Prediction of Advanced Axillary Lymph Node Metastases (ypN2-3) Using Breast MR
      imaging and PET/CT after Neoadjuvant Chemotherapy in Invasive Ductal Carcinoma
      Patients.
AB  - We aimed to investigate the value of breast magnetic resonance (MR) imaging and
      positron emission tomography-computed tomography (PET/CT) in predicting advanced
      axillary lymph node (ALN) metastases (ypN2-3) after neoadjuvant chemotherapy
      (NAC) in invasive ductal carcinoma patients. A total of 108 patients with
      invasive ductal carcinoma underwent breast MR imaging and PET/CT both before and
      after NAC (termed initial staging and restaging, respectively). The number of
      positive ALNs and the short diameter (SD) of the largest ALN on breast MR imaging
      and maximal standardized uptake value (SUVmax) in the ALNs on PET/CT were
      evaluated. Odds ratio (OR) for prediction of advanced ALN metastases was
      calculated. The negative predictive value (NPV) of restaging imaging for
      exclusion of advanced ALN metastases was also calculated. Patients with advanced
      ALN metastases were more likely to have a higher number (>=2) of positive LNs
      (OR, 8.06; P = 0.015) on restaging MR imaging. No clinico-pathological factors
      were significantly associated with advanced ALN metastases. With restaging MR
      imaging, PET/CT, and MR imaging plus PET/CT, the NPV for excluding advanced ALN
      metastases was 97.3%, 94.4%, and 100.0%. A higher number of positive ALNs on
      restaging MR imaging was an independent predictor for advanced ALN metastases
      after NAC.

PMID- 29453386
TI  - Anti-fibrotic Effects of CXCR4-Targeting i-body AD-114 in Preclinical Models of
      Pulmonary Fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease that is
      prevalent in individuals >50 years of age, with a median survival of 3-5 years
      and limited therapeutic options. The disease is characterized by collagen
      deposition and remodeling of the lung parenchyma in a process that is thought to
      be driven by collagen-expressing immune and structural cells. The G-protein
      coupled C-X-C chemokine receptor 4, CXCR4, is a candidate therapeutic target for
      IPF owing to its role in the recruitment of CXCR4+ fibrocytes from the bone
      marrow to fibrotic lung tissue and its increased expression levels by structural
      cells in fibrotic lung tissue. We have engineered a novel fully human single
      domain antibody "i-body" called AD-114 that binds with high affinity to human
      CXCR4. We demonstrate here that AD-114 inhibits invasive wound healing and
      collagen 1 secretion by human IPF fibroblasts but not non-diseased control lung
      fibroblasts. Furthermore, in a murine bleomycin model of pulmonary fibrosis, AD
      114 reduced the accumulation of fibrocytes (CXCR4+/Col1+/CD45+) in fibrotic
      murine lungs and ameliorated the degree of lung injury. Collectively, these
      studies demonstrate that AD-114 holds promise as a new biological therapeutic for
      the treatment of IPF.

PMID- 29453387
TI  - Structural determinants of the SINE B2 element embedded in the long non-coding
      RNA activator of translation AS Uchl1.
AB  - Pervasive transcription of mammalian genomes leads to a previously underestimated
      level of complexity in gene regulatory networks. Recently, we have identified a
      new functional class of natural and synthetic antisense long non-coding RNAs
      (lncRNA) that increases translation of partially overlapping sense mRNAs. These
      molecules were named SINEUPs, as they require an embedded inverted SINE B2
      element for their UP-regulation of translation. Mouse AS Uchl1 is the
      representative member of natural SINEUPs. It was originally discovered for its
      role in increasing translation of Uchl1 mRNA, a gene associated with
      neurodegenerative diseases. Here we present the secondary structure of the SINE
      B2 Transposable Element (TE) embedded in AS Uchl1. We find that specific
      structural regions, containing a short hairpin, are required for the ability of
      AS Uchl1 RNA to increase translation of its target mRNA. We also provide a high
      resolution structure of the relevant hairpin, based on NMR observables. Our
      results highlight the importance of structural determinants in embedded TEs for
      their activity as functional domains in lncRNAs.

PMID- 29453388
TI  - Identifying noncoding risk variants using disease-relevant gene regulatory
      networks.
AB  - Identifying noncoding risk variants remains a challenging task. Because noncoding
      variants exert their effects in the context of a gene regulatory network (GRN),
      we hypothesize that explicit use of disease-relevant GRNs can significantly
      improve the inference accuracy of noncoding risk variants. We describe Annotation
      of Regulatory Variants using Integrated Networks (ARVIN), a general computational
      framework for predicting causal noncoding variants. It employs a set of novel
      regulatory network-based features, combined with sequence-based features to infer
      noncoding risk variants. Using known causal variants in gene promoters and
      enhancers in a number of diseases, we show ARVIN outperforms state-of-the-art
      methods that use sequence-based features alone. Additional experimental
      validation using reporter assay further demonstrates the accuracy of ARVIN.
      Application of ARVIN to seven autoimmune diseases provides a holistic view of the
      gene subnetwork perturbed by the combinatorial action of the entire set of risk
      noncoding mutations.

PMID- 29453389
TI  - Toxicity Classification of Oxide Nanomaterials: Effects of Data Gap Filling and
      PChem Score-based Screening Approaches.
AB  - Development of nanotoxicity prediction models is becoming increasingly important
      in the risk assessment of engineered nanomaterials. However, it has significant
      obstacles caused by the wide heterogeneities of published literature in terms of
      data completeness and quality. Here, we performed a meta-analysis of 216
      published articles on oxide nanoparticles using 14 attributes of physicochemical,
      toxicological and quantum-mechanical properties. Particularly, to improve
      completeness and quality of the extracted dataset, we adapted two preprocessing
      approaches: data gap-filling and physicochemical property based scoring.
      Performances of nano-SAR classification models revealed that the dataset with the
      highest score value resulted in the best predictivity with compromise in its
      applicability domain. The combination of physicochemical and toxicological
      attributes was proved to be more relevant to toxicity classification than quantum
      mechanical attributes. Overall, by adapting these two preprocessing methods, we
      demonstrated that meta-analysis of nanotoxicity literatures could provide an
      effective alternative for the risk assessment of engineered nanomaterials.

PMID- 29453390
TI  - Birds and beans: Comparing avian richness and endemism in arabica and robusta
      agroforests in India's Western Ghats.
AB  - Coffee is a major tropical commodity crop that can provide supplementary habitat
      for native wildlife. In Asia, coffee production is an increasingly important
      driver of landscape transformation and shifts between different coffee species is
      a major dimension of agroforestry trends. Yet few studies have compared the
      ecological impacts of conversion between different coffee species. We evaluated
      whether or not the two species of coffee grown globally-Coffea arabica and C.
      canephora (denoted "robusta")-had equivalent avian conservation value in the
      Western Ghats, India, where robusta production has become increasingly dominant.
      We found that habitat specialist and functional guild diversity was higher in
      arabica, and that arabica was more profitable. However, robusta farms generally
      supported the same or slightly higher abundances of habitat specialists and
      functional guilds, largely due to dense canopy and landscape-level forest cover.
      Farming practices, chiefly pesticide use, may affect the suitability of coffee
      agroforests as habitat for avian specialists, and at present, robusta farmers
      tended to use less pesticide. Given future projections for arabica to robusta
      conversion in tropical Asia, our study indicates that certification efforts
      should prioritize maintaining native canopy shade trees and forest cover to
      ensure that coffee landscapes can continue providing biodiversity benefits.

PMID- 29453391
TI  - Diffusion mechanism in the sodium-ion battery material sodium cobaltate.
AB  - High performance batteries based on the movement of Li ions in Li x CoO2 have
      made possible a revolution in mobile electronic technology, from laptops to
      mobile phones. However, the scarcity of Li and the demand for energy storage for
      renewables has led to intense interest in Na-ion batteries, including
      structurally-related Na x CoO2. Here we have determined the diffusion mechanism
      for Na0.8CoO2 using diffuse x-ray scattering, quasi-elastic neutron scattering
      and ab-initio molecular dynamics simulations, and we find that the sodium
      ordering provides diffusion pathways and governs the diffusion rate. Above T ~
      290 K the so-called partially disordered stripe superstructure provides channels
      for quasi-1D diffusion, and melting of the sodium ordering leads to 2D superionic
      diffusion above T ~ 370 K. We obtain quantitative agreement between our
      microscopic study of the hopping mechanism and bulk self-diffusion measurements.
      Our approach can be applied widely to other Na- or Li-ion battery materials.

PMID- 29453392
TI  - A novel flatworm-specific gene implicated in reproduction in Macrostomum lignano.
AB  - Free-living flatworms, such as the planarian Schmidtea mediterranea, are
      extensively used as model organisms to study stem cells and regeneration. The
      majority of flatworm studies so far focused on broadly conserved genes. However,
      investigating what makes these animals different is equally informative for
      understanding its biology and might have biomedical value. We re-analyzed the
      neoblast and germline transcriptional signatures of the flatworm M. lignano using
      an improved transcriptome assembly and show that germline-enriched genes have a
      high fraction of flatworm-specific genes. We further identified the Mlig-sperm1
      gene as a member of a novel gene family conserved only in free-living flatworms
      and essential for producing healthy spermatozoa. In addition, we established a
      whole-animal electron microscopy atlas (nanotomy) to visualize the ultrastructure
      of the testes in wild type worms, but also as a reference platform for different
      ultrastructural studies in M. lignano. This work demonstrates that investigation
      of flatworm-specific genes is crucial for understanding flatworm biology and
      establishes a basis for such future research in M. lignano.

PMID- 29453393
TI  - Adherence to antiretroviral therapy and factors affecting low medication
      adherence among incident HIV-infected individuals during 2009-2016: A nationwide
      study.
AB  - For ideal clinical benefit, human immunodeficiency virus (HIV)-infected
      individuals should receive continuous medication. This is the first nationwide
      antiretroviral therapy (ART) adherence study in Asia, where medication monitoring
      at national level is systemically available. We estimated the ART adherence of
      incident HIV-infected individuals and investigated factors affecting low
      medication adherence using the national health insurance (NHI) claims data from
      2007 to 2016. Medication possession ratio (MPR) was used to measure medication
      adherence and risk factors were identified by multivariable logistic regression
      analysis. Of the 8,501 newly diagnosed HIV-infected individuals during 2009-2016
      with at least one ART prescription, 70.4% of HIV patients had adequate adherence
      to ART defined as MPR >=95%. Requiring prophylactic antibiotics, female gender,
      age of 0-19 and same or over 50 s compared to 30-39, and having a history of
      malignancy, lower socioeconomic status, not visiting tertiary hospital, and being
      diagnosed in the earlier years were risk factors for lower adherence (Odds ratio
      1.7, 1.6, 1.6, 1.4, 1.6, 2.1, 1.2, and 1.6 to 3.8 respectively). Health authority
      should take into consideration of these modifiable and unmodifiable barriers to
      establish sustainable monitoring system at national level and to improve
      adherence.

PMID- 29453394
TI  - Experimental modelling of cardiac pressure overload hypertrophy: Modified
      technique for precise, reproducible, safe and easy aortic arch banding-debanding
      in mice.
AB  - Pressure overload left ventricular hypertrophy is a known precursor of heart
      failure with ominous prognosis. The development of experimental models that
      reproduce this phenomenon is instrumental for the advancement in our
      understanding of its pathophysiology. The gold standard of these models is the
      controlled constriction of the mid aortic arch in mice according to Rockman's
      technique (RT). We developed a modified technique that allows individualized and
      fully controlled constriction of the aorta, improves efficiency and generates a
      reproducible stenosis that is technically easy to perform and release. An
      algorithm calculates, based on the echocardiographic arch diameter, the intended
      perimeter at the constriction, and a suture is prepared with two knots separated
      accordingly. The aorta is encircled twice with the suture and the loop is closed
      with a microclip under both knots. We performed controlled aortic constriction
      with Rockman's and the double loop-clip (DLC) techniques in mice. DLC proved
      superiority in efficiency (mortality and invalid experiments) and more
      homogeneity of the results (transcoarctational gradients, LV mass, cardiomyocyte
      hypertrophy, gene expression) than RT. DLC technique optimizes animal use and
      generates a consistent and customized aortic constriction with homogeneous LV
      pressure overload morphofunctional, structural, and molecular features.

PMID- 29453395
TI  - The genes of the sulphoquinovose catabolism in Escherichia coli are also
      associated with a previously unknown pathway of lactose degradation.
AB  - Comparative genomics analysis of conserved gene cassettes demonstrated
      resemblance between a recently described cassette of genes involved in
      sulphoquinovose degradation in Escherichia coli K-12 MG1655 and a Bacilli
      cassette linked with lactose degradation. Six genes from both cassettes had
      similar functions related to carbohydrate metabolism, namely, hydrolase,
      aldolase, kinase, isomerase, transporter, and transcription factor. The
      Escherichia coli sulphoglycolysis cassette was thus predicted to be associated
      with lactose degradation. This prediction was confirmed experimentally:
      expression of genes coding for aldolase (yihT), isomerase (yihS), and kinase
      (yihV) was dramatically increased during growth on lactose. These genes were
      previously shown to be activated during growth on sulphoquinovose, so our
      observation may indicate multi-functional capabilities of the respective
      proteins. Transcription starts for yihT, yihV and yihW were mapped in silico, in
      vitro and in vivo. Out of three promoters for yihT, one was active only during
      growth on lactose. We further showed that switches in yihT transcription are
      controlled by YihW, a DeoR-family transcription factor in the Escherichia coli
      cassette. YihW acted as a carbon source-dependent dual regulator involved in
      sustaining the baseline growth in the absence of lac-operon, with function either
      complementary, or opposite to a global regulator of carbohydrate metabolism, cAMP
      CRP.

PMID- 29453396
TI  - Bone marrow lympho-myeloid malfunction in obesity requires precursor cell
      autonomous TLR4.
AB  - Obesity, a prevalent condition in adults and children, impairs bone marrow (BM)
      function. However, the underlying mechanisms are unclear. Here, we show that
      obese mice exhibit poor emergency immune responses in a toll-like receptor 4
      (TLR4)-dependent manner. Canonical myeloid genes (Csf1r, Spi1, Runx1) are
      enhanced, and lymphoid genes (Flt3, Tcf3, Ebf1) are reduced. Using adoptive
      transfer and mixed BM chimera approaches we demonstrate that myeloid>lymphoid
      bias arises after 6 weeks of high-fat diet and depends on precursor cell
      autonomous TLR4. Further, lean mice exposed to the TLR4 ligand lipopolysaccharide
      (LPS) at doses similar to that detectable in obese serum recapitulates BM lympho
      myeloid alterations. Together, these results establish a mechanistic contribution
      of BM cell-intrinsic TLR4 to obesity-driven BM malfunction and demonstrate the
      importance of LPS. Our findings raises important questions about the impact of
      maternal obesity and endotoxemia to fetal hematopoiesis, as fetal immune
      precursors are also sensitive to TLR4 signals.

PMID- 29453397
TI  - Temperature Dependence of the Dielectric Function of Monolayer MoSe2.
AB  - The dielectric function [Formula: see text] of monolayer molybdenum diselenide
      (MoSe2) is obtained and analyzed at temperatures from 31 to 300 K and at energies
      from 0.74 to 6.42 eV. The sample is a large-area, partially discontinuous
      monolayer (submonolayer) film of MoSe2 grown on a sapphire substrate by
      selenization of pulsed laser deposited MoO3 film. Morphological and optical
      characterizations verified the excellent quality of the film. The MoSe2 data were
      analyzed using the effective medium approximation, which treats the film and bare
      substrate regions as a single layer. Second derivatives of epsilon with respect
      to energy were numerically calculated and analyzed with standard lineshapes to
      extract accurate critical-point (CP) energies. We find only 6 CPs for monolayer
      MoSe2 at room temperature. At cryogenic temperatures 6 additional structures are
      resolved. The separations in the B- and C-excitonic peaks are also observed. All
      structures blue-shift and sharpen with decreasing temperature as a result of the
      reducing lattice constant and electron-phonon interactions. The temperature
      dependences of the CP energies were determined by fitting the data to the
      phenomenological expression that contains the Bose-Einstein statistical factor
      and the temperature coefficient.

PMID- 29453398
TI  - Host defense against oral microbiota by bone-damaging T cells.
AB  - The immune system evolved to efficiently eradicate invading bacteria and
      terminate inflammation through balancing inflammatory and regulatory T-cell
      responses. In autoimmune arthritis, pathogenic TH17 cells induce bone destruction
      and autoimmune inflammation. However, whether a beneficial function of T-cell
      induced bone damage exists is unclear. Here, we show that bone-damaging T cells
      have a critical function in the eradication of bacteria in a mouse model of
      periodontitis, which is the most common infectious disease. Bacterial invasion
      leads to the generation of specialized TH17 cells that protect against bacteria
      by evoking mucosal immune responses as well as inducing bone damage, the latter
      of which also inhibits infection by removing the tooth. Thus, bone-damaging T
      cells, which may have developed to stop local infection by inducing tooth loss,
      function as a double-edged sword by protecting against pathogens while also
      inducing skeletal tissue degradation.

PMID- 29453400
TI  - A survey of metastasis suppressors in Metazoa.
AB  - Metastasis suppressors are genes/proteins involved in regulation of one or more
      steps of the metastatic cascade while having little or no effect on tumor growth.
      The list of putative metastasis suppressors is constantly increasing although
      thorough understanding of their biochemical mechanism(s) and evolutionary history
      is still lacking. Little is known about tumor-related genes in invertebrates,
      especially non-bilaterians and unicellular relatives of animals. However, in the
      last few years we have been witnessing a growing interest in this subject since
      it has been shown that many disease-related genes are already present in simple
      non-bilateral animals and even in their unicellular relatives. Studying human
      diseases using simpler organisms that may better represent the ancestral
      conditions in which the specific disease-related genes appeared could provide
      better understanding of how those genes function. This review represents a
      compilation of published literature and our bioinformatics analysis to gain a
      general insight into the evolutionary history of metastasis-suppressor genes in
      animals (Metazoa). Our survey suggests that metastasis-suppressor genes emerged
      in three different periods in the evolution of Metazoa: before the origin of
      metazoans, with the emergence of first animals and at the origin of vertebrates.

PMID- 29453399
TI  - Association of Sleep and Circadian Activity Rhythm with Emotional Face Processing
      among 12-month-old Infants.
AB  - Sleep and circadian rhythmicity both play an important role in human's cognitive
      functioning, yet the way in which early development of sleep and circadian rhythm
      affects cognitive processes and social learning in infants remains less
      understood. We examined the association of sleep and circadian activity rhythm
      (CAR) with face and emotional information processing in 12-month old infants.
      Face processing was measured by eye tracking, whereby infants' scanning patterns
      and pupil dilations were calculated when they were presented with neutral,
      pleasant and unpleasant faces. Infants with better sleep quality (i.e., less
      waking after sleep onset) and lower sleep-wake pattern variability (i.e., higher
      inter-daily stability) exhibited a higher eyes over mouth fixation ratio (EMR).
      Infants with longer total sleep time showed larger pupil diameter changes in
      response to emotional facial expressions, more closely resembling the responses
      of adults. Our findings suggest the role of sleep and circadian rhythm in waking
      cognition and have implications for understanding the early development of social
      learning in young children.

PMID- 29453401
TI  - Endothelial smoothened-dependent hedgehog signaling is not required for sonic
      hedgehog induced angiogenesis or ischemic tissue repair.
AB  - Sonic Hedgehog (Shh) signaling induces neovascularization and angiogenesis. It is
      not known whether the hedgehog signaling pathway in endothelial cells is
      essential to angiogenesis. Smoothened (Smo) transduces hedgehog signaling across
      the cell membrane. This study assessed whether endothelial Smoothened-dependent
      Shh signaling is required for Shh-mediated angiogenesis and ischemic tissue
      repair. Endothelial-specific smoothened knockout mice, eSmoNull were created
      using Cre-lox recombination system. eSmoNull mice had no observable phenotype at
      baseline and showed normal cardiac function. Smoothened in CD31+ cells isolated
      from eSmoNull hearts was significantly reduced compared to CD31+ cells from
      eSmoWT littermate control hearts. Fluorescence immunostaining of eSmoNull heart
      sections showed Smo expression in endothelial cells was abolished. The hind-limb
      ischemia (HLI) model was used to assess the response to ischemic injury.
      Perfusion ratio, limb motor function, and limb necrosis were not significantly
      different after HLI between eSmoNull mice and eSmoWT. Capillary densities in the
      ischemic limb in eSmoNull mice were also similar to eSmoWT at 4 weeks after HLI.
      Next, response to exogenous Shh was assessed in the corneal angiogenesis model.
      There was no significant difference in corneal angiogenesis induced by
      administration of Shh pellets between eSmoWT and eSmoNull mice. Furthermore, in
      vitro experiments demonstrated that direct Shh had limited effects on endothelial
      cell proliferation and migration. However, conditioned media from Shh-treated
      fibroblasts had a more potent effect on endothelial cell proliferation and
      migration than non-treated conditioned media. Furthermore, Shh treatment of
      fibroblasts dramatically stimulated angiogenic growth factor expression,
      including PDGF-B, VEGF-A, HGF and IGF. PDGF-B was the most upregulated and may
      contribute to the large neo-vessels associated with Shh-induced angiogenesis.
      Taken together, these data demonstrate that Shh signaling via Smoothened in
      endothelial cells is not required for angiogenesis and ischemic tissue repair.
      Shh signaling via stromal cells likely mediates its angiogenic effects.

PMID- 29453402
TI  - A soft lithographic approach to fabricate InAs nanowire field-effect transistors.
AB  - The epitaxial layer transfer process was previously introduced to integrate high
      quality and ultrathin III-V compound semiconductor layers on any substrate.
      However, this technique has limitation for fabrication of sub-micron nanoribbons
      due to the diffraction limit of photolithography. In order to overcome this
      limitation and scale down its width to sub-50 nm, we need either a costly short
      wavelength lithography system or a non-optical patterning method. In this work,
      high-quality III-V compound semiconductor nanowires were fabricated and
      integrated onto a Si/SiO2 substrate by a soft-lithography top-down approach and
      an epitaxial layer transfer process, using MBE-grown ultrathin InAs as a source
      wafer. The width of the InAs nanowires was controlled using solvent-assisted
      nanoscale embossing (SANE), descumming, and etching processes. By optimizing
      these processes, NWs with a width less than 50 nm were readily obtained. The InAs
      NWFETs prepared by our method demonstrate peak electron mobility of ~1600 cm2/Vs,
      indicating negligible material degradation during the SANE process.

PMID- 29453403
TI  - Tailoring of magnetoimpedance effect and magnetic softness of Fe-rich glass
      coated microwires by stress- annealing.
AB  - There is a pressing need for improving of the high-frequency magneto-impedance
      effect of cost-effective soft magnetic materials for use in high-performance
      sensing devices. The impact of the stress-annealing on magnetic properties and
      high frequency impedance of Fe-rich glass-coated microwires was studied.
      Hysteresis loops of Fe-rich microwires have been considerably affected by stress-
      annealing. In stress-annealed Fe- rich microwire we obtained drastic decreasing
      of coercivity and change of character of hysteresis loop from rectangular to
      linear. By controlling stress-annealing conditions (temperature and time) we
      achieved drastic increasing (by order of magnitude) of giant magnetoimpedance
      ratio. Coercivity, remanent magnetization, diagonal and of-diagonal
      magnetoimpedance effect of Fe-rich microwires can be tuned by stress-annealing
      conditions: annealing temperature and time. Observed experimental results are
      discussed considering relaxation of internal stresses, compressive "back
      stresses" arising after stress annealing and topological short range ordering.

PMID- 29453404
TI  - PREP1 tumor suppressor protects the late-replicating DNA by controlling its
      replication timing and symmetry.
AB  - The synthesis of middle-to-late-replicating DNA can be affected independently of
      the rest of the genome by down-regulating the tumor suppressor PREP1 (PKNOX1).
      Indeed, DNA combing shows that PREP1 down-regulation affects DNA replication
      rate, increases the number of simultaneously firing origins and the asymmetry of
      DNA replication, leading to DNA damage. Genome-wide analysis of replication
      timing by Repli-seq shows that, upon PREP1 down-regulation, 25% of the genome is
      replicated earlier in the S-phase. The targeted DNA sequences correspond to Lamin
      Associated Domains (LADs), and include late-replicating (LRRs) and temporal
      transition regions (TTRs). Notably, the distribution of PREP1 DNA binding sites
      and of its target genes indicates that DNA replication defects are independent of
      the overall PREP1 transcriptional activity. Finally, PREP1 down-regulation causes
      a substantial decrease in Lamin B1 levels. This suggests that DNA is released
      from the nuclear lamina earlier than in the control cells and is available for
      replication, thus explaining timing defects and DNA damage.This is the first
      evidence that the replication timing of a specific fraction of the human genome
      is affected by PREP1 tumor suppressor. This previously unknown function might
      significantly contribute to the genomic instability observed in human tumors.

PMID- 29453405
TI  - Widespread use of incorrect PCR ramp rate negatively impacts multidrug-resistant
      tuberculosis diagnosis (MTBDRplus).
AB  - The scale-up of rapid drug resistance testing for TB is a global priority.
      MTBDRplus is a WHO-endorsed multidrug-resistant (MDR)-TB PCR assay with
      suboptimal sensitivities and high indeterminate rates on smear-negative
      specimens. We hypothesised that widespread use of incorrect thermocycler ramp
      rate (speed of temperature change between cycles) impacts performance. A global
      sample of 72 laboratories was surveyed. We tested 107 sputa from Xpert MTB/RIF
      positive patients and, separately, dilution series of bacilli, both at the
      manufacturer-recommended ramp rate (2.2  degrees C/s) and the most frequently
      reported incorrect ramp rate (4.0  degrees C/s). Mycobacterium tuberculosis
      complex DNA (TUB-band)-detection, indeterminate results, accuracy, and inter
      reader variability (dilution series only) were compared. 32 respondents did a
      median (IQR) of 41 (20-150) assays monthly. 78% used an incorrect ramp rate. On
      smear-negative sputa, 2.2  degrees C/s vs. 4.0  degrees C/s improved TUB-band
      positivity (42/55 vs. 32/55; p = 0.042) and indeterminate rates (1/42 vs. 5/32; p
      = 0.039). The actionable results (not TUB-negative or indeterminate; 41/55 vs.
      28/55) hence improved by 21% (95% CI: 9-35%). Widespread use of incorrect ramp
      rate contributes to suboptimal MTBDRplus performance on smear-negative specimens
      and hence limits clinical utility. The number of diagnoses (and thus the number
      of smear-negative patients in whom DST is possible) will improve substantially
      after ramp rate correction.

PMID- 29453406
TI  - CRISPR-Cas9, a tool to efficiently increase the development of recombinant
      African swine fever viruses.
AB  - African swine fever virus (ASFV) causes a highly contagious disease called
      African swine fever. This disease is often lethal for domestic pigs, causing
      extensive losses for the swine industry. ASFV is a large and complex double
      stranded DNA virus. Currently there is no commercially available treatment or
      vaccine to prevent this devastating disease. Development of recombinant ASFV for
      producing live-attenuated vaccines or studying the involvement of specific genes
      in virus virulence has relied on the relatively rare event of homologous
      recombination in primary swine macrophages, causing difficulty to purify the
      recombinant virus from the wild-type parental ASFV. Here we present the use of
      the CRISPR-Cas9 gene editing system as a more robust and efficient system to
      produce recombinant ASFVs. Using CRISPR-Cas9 a recombinant virus was efficiently
      developed by deleting the non-essential gene 8-DR from the genome of the highly
      virulent field strain Georgia07 using swine macrophages as cell substrate.

PMID- 29453407
TI  - Neovasculature can be induced by patching an arterial graft into a vein: A novel
      in vivo model of spontaneous arteriovenous fistula formation.
AB  - Arteriovenous malformations consist of tangles of arteries and veins that are
      often connected by a fistula. The causes and mechanisms of these clinical
      entities are not fully understood. We discovered that suturing an arterial patch
      into the common jugular vein of rabbits led to spontaneous neovascularization,
      the formation of an arteriovenous fistula and the development of an arteriovenous
      shunt. An arterial patch excised from the common carotid artery was sutured into
      the common jugular vein. Within a month, a dense nidus-like neovasculature formed
      around the patch. Angiography and pulse-oximeter analyses showed that the blood
      flowing into the neovasculature was arterial blood. This indicated that an
      arteriovenous shunt had formed. Fluorescence in situ hybridization with a Y
      chromosome probe in female rabbits that received an arterial patch from male
      rabbits showed that the vessels close to the graft bore the Y chromosome, whereas
      the vessels further away did not. Enzyme-linked immunosorbent assays and cDNA
      microarray analysis showed that multiple angiogenic factors were upregulated
      after patch transplantation. This is the first in vivo model of spontaneous
      arteriovenous fistula formation. Further research on these differences may help
      to improve understanding of human vascular anomaly diseases and the basic
      principles underlying vasculogenesis and/or angiogenesis.

PMID- 29453408
TI  - Biosignals reflect pair-dynamics in collaborative work: EDA and ECG study of pair
      programming in a classroom environment.
AB  - Collaboration is a complex phenomenon, where intersubjective dynamics can greatly
      affect the productive outcome. Evaluation of collaboration is thus of great
      interest, and can potentially help achieve better outcomes and performance.
      However, quantitative measurement of collaboration is difficult, because much of
      the interaction occurs in the intersubjective space between collaborators. Manual
      observation and/or self-reports are subjective, laborious, and have a poor
      temporal resolution. The problem is compounded in natural settings where task
      activity and response-compliance cannot be controlled. Physiological signals
      provide an objective mean to quantify intersubjective rapport (as synchrony), but
      require novel methods to support broad deployment outside the lab. We studied 28
      student dyads during a self-directed classroom pair-programming exercise.
      Sympathetic and parasympathetic nervous system activation was measured during
      task performance using electrodermal activity and electrocardiography. Results
      suggest that (a) we can isolate cognitive processes (mental workload) from
      confounding environmental effects, and (b) electrodermal signals show role
      specific but correlated affective response profiles. We demonstrate the potential
      for social physiological compliance to quantify pair-work in natural settings,
      with no experimental manipulation of participants required. Our objective
      approach has a high temporal resolution, is scalable, non-intrusive, and robust.

PMID- 29453409
TI  - A Potential Prognostic Long Noncoding RNA Signature to Predict Recurrence among
      ER-positive Breast Cancer Patients Treated with Tamoxifen.
AB  - Limited predictable long noncoding RNA (lncRNA) signature was reported in
      tamoxifen resistance among estrogen receptor (ER)-positive breast cancer (BC)
      patients. The aim of this study was to identify and assess prognostic lncRNA
      signature to predict recurrence among ER-positive BC patients treated with
      tamoxifen. Cohorts from Gene Expression Omnibus (GEO) (n = 298) and The Cancer
      Genome Atlas (TCGA) (n = 160) were defined as training and validation cohort,
      respectively. BC relapse associated lnRNAs was identify within training cohort,
      and the predictable value of recurrence was assessed in both cohorts. A total of
      11lncRNAs were recognized to be associated with relapse free survival (RFS) of ER
      positive BC patients receiving tamoxifen, who were divided into low-risk and high
      risk group on basis of relapse risk scores (RRS). Multivariate cox regression
      analyses revealed that the RRS is an independent prognostic biomarker in the
      prediction of ER-positive BC patients' survival. GSEA indicated that high-risk
      group was associated with several signaling pathways in processing of BC
      recurrence and metastasis such as PI3K-Akt and Wnt signaling. Our 11-lncRNA based
      classifier is a reliable prognostic and predictive tool for disease relapse in BC
      patients receiving tamoxifen.

PMID- 29453410
TI  - Molecular characterization of colorectal adenomas with and without malignancy
      reveals distinguishing genome, transcriptome and methylome alterations.
AB  - The majority of colorectal cancer (CRC) arises from precursor lesions known as
      polyps. The molecular determinants that distinguish benign from malignant polyps
      remain unclear. To molecularly characterize polyps, we utilized Cancer Adjacent
      Polyp (CAP) and Cancer Free Polyp (CFP) patients. CAPs had tissues from the
      residual polyp of origin and contiguous cancer; CFPs had polyp tissues matched to
      CAPs based on polyp size, histology and dysplasia. To determine whether molecular
      features distinguish CAPs and CFPs, we conducted Whole Genome Sequencing, RNA
      seq, and RRBS on over 90 tissues from 31 patients. CAPs had significantly more
      mutations, altered expression and hypermethylation compared to CFPs. APC was
      significantly mutated in both polyp groups, but mutations in TP53, FBXW7, PIK3CA,
      KIAA1804 and SMAD2 were exclusive to CAPs. We found significant expression
      changes between CAPs and CFPs in GREM1, IGF2, CTGF, and PLAU, and both expression
      and methylation alterations in FES and HES1. Integrative analyses revealed 124
      genes with alterations in at least two platforms, and ERBB3 and E2F8 showed
      aberrations specific to CAPs across all platforms. These findings provide a
      resource of molecular distinctions between polyps with and without cancer, which
      have the potential to enhance the diagnosis, risk assessment and management of
      polyps.

PMID- 29453411
TI  - The impact of a helminth-modified microbiome on host immunity.
AB  - Intestinal helminths have well-characterized modulatory effects on mammalian
      immune pathways. Ongoing helminth infection has been associated with both the
      suppression of allergies and an altered susceptibility to microbial infections.
      Enteric helminths share a niche with the intestinal microbiota, and the presence
      of helminths alters the microbiota composition and the metabolic signature of the
      host. Recent studies have demonstrated that the helminth-modified intestinal
      microbiome has the capacity to modify host immune responses even in the absence
      of live helminth infection. This article discusses the mechanisms by which
      helminths modify the intestinal microbiome of mammals, and reviews the evidence
      for a helminth-modified microbiome directly influencing host immunity during
      infectious and inflammatory diseases. Understanding the multifaceted mechanisms
      that underpin helminth immunomodulation will pave the way for novel therapies to
      combat infectious and inflammatory diseases.

PMID- 29453412
TI  - Pulmonary antigen encounter regulates the establishment of tissue-resident CD8
      memory T cells in the lung airways and parenchyma.
AB  - Resident memory CD8 T (TRM) cells in the lung parenchyma (LP) and airways provide
      heterologous protection against influenza virus challenge. However, scant
      knowledge exists regarding factors necessary to establish and maintain lung CD8
      TRM. Here we demonstrate that, in contrast to mechanisms described for other
      tissues, airway, and LP CD8 TRM establishment requires cognate antigen
      recognition in the lung. Systemic effector CD8 T cells could be transiently
      pulled into the lung in response to localized inflammation, however these
      effector cells failed to establish tissue residency unless antigen was present in
      the pulmonary environment. The interaction of effector CD8 T cells with cognate
      antigen in the lung resulted in increased and prolonged expression of the tissue
      retention markers CD69 and CD103, and increased expression of the adhesion
      molecule VLA-1. The inability of localized inflammation alone to establish lung
      TRM resulted in decreased viral clearance and increased mortality following
      heterosubtypic influenza challenge, despite equal numbers of circulating memory
      CD8 T cells. These findings demonstrate that pulmonary antigen encounter is
      required for the establishment of lung CD8 TRM and may inform future vaccine
      strategies to generate robust cellular immunity against respiratory pathogens.

PMID- 29453413
TI  - Depression and obesity: evidence of shared biological mechanisms.
AB  - Depression and obesity are common conditions with major public health
      implications that tend to co-occur within individuals. The relationship between
      these conditions is bidirectional: the presence of one increases the risk for
      developing the other. It has thus become crucial to gain a better understanding
      of the mechanisms responsible for the intertwined downward physiological spirals
      associated with both conditions. The present review focuses specifically on
      shared biological pathways that may mechanistically explain the depression
      obesity link, including genetics, alterations in systems involved in homeostatic
      adjustments (HPA axis, immuno-inflammatory activation, neuroendocrine regulators
      of energy metabolism including leptin and insulin, and microbiome) and brain
      circuitries integrating homeostatic and mood regulatory responses. Furthermore,
      the review addresses interventional opportunities and questions to be answered by
      future research that will enable a comprehensive characterization and targeting
      of the biological links between depression and obesity.

PMID- 29453414
TI  - Chemisorption of polysulfides through redox reactions with organic molecules for
      lithium-sulfur batteries.
AB  - Lithium-sulfur battery possesses high energy density but suffers from severe
      capacity fading due to the dissolution of lithium polysulfides. Novel design and
      mechanisms to encapsulate lithium polysulfides are greatly desired by high
      performance lithium-sulfur batteries towards practical applications. Herein, we
      report a strategy of utilizing anthraquinone, a natural abundant organic
      molecule, to suppress dissolution and diffusion of polysulfides species through
      redox reactions during cycling. The keto groups of anthraquinone play a critical
      role in forming strong Lewis acid-based chemical bonding. This mechanism leads to
      a long cycling stability of sulfur-based electrodes. With a high sulfur content
      of ~73%, a low capacity decay of 0.019% per cycle for 300 cycles and retention of
      81.7% over 500 cycles at 0.5 C rate can be achieved. This finding and
      understanding paves an alternative avenue for the future design of sulfur-based
      cathodes toward the practical application of lithium-sulfur batteries.

PMID- 29453415
TI  - ERLIN1 mutations cause teenage-onset slowly progressive ALS in a large Turkish
      pedigree.
AB  - Amyotrophic lateral sclerosis (ALS) is a late-onset motor neuron disease with
      mostly dominant inheritance and a life expectancy of 2-5 years; however, a quite
      common occurrence of atypical forms of the disease, due to recessive inheritance,
      has become evident with the use of NGS technologies. In this paper, we describe a
      family with close consanguinity for at least four generations, suffering from a
      slowly progressive form of ALS. Spastic walking is observed since teenage years,
      while bulbar symptoms start much later, at the fifth or sixth decade of life.
      Patients usually die because of respiratory failure. Using whole-exome
      sequencing, we identified a novel homozygous p.(Val94Ala) (c.281T>C)
      (NG_052910.1) (NM_006459) variation in the endoplasmic reticulum lipid raft
      associated protein 1 (ERLIN1) gene, which segregates with the disease in the
      family. Here we suggest that ERLIN1 variants, previously shown in juvenile
      hereditary spastic paraplegia cases, may also be the cause of a slowly
      progressive early-onset ALS, starting with upper motor neuron features and
      developing into classical ALS with the addition of lower motor neuron
      dysfunction. We also demonstrate that ATP-binding cassette subfamily C member 2
      (ABCC2) gene, responsible for hyperbilirubinemia, is linked to ERLIN1.

PMID- 29453416
TI  - Homozygous deletion in MYL9 expands the molecular basis of megacystis-microcolon
      intestinal hypoperistalsis syndrome.
AB  - Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a severe
      disease characterized by functional obstruction in the urinary and
      gastrointestinal tract. The molecular basis of this condition started to be
      defined recently, and the genes related to the syndrome (ACTG2-heterozygous
      variant in sporadic cases; and MYH11 (myosin heavy chain 11), LMOD1 (leiomodin 1)
      and MYLK (myosin light chain (MLC) kinase)-autosomal recessive inheritance),
      encode proteins involved in the smooth muscle contraction, supporting a myopathic
      basis for the disease. In the present article, we described a family with two
      affected siblings with MMIHS born to consanguineous parents and the molecular
      investigation performed to define the genetic etiology. Previous whole exome
      sequencing of the affected child and parents did not identify a candidate gene
      for the disease in this family, but now we present a reanalysis of the data that
      led to the identification of a homozygous deletion encompassing the last exon of
      MYL9 (myosin regulatory light chain 9) in the affected individual. MYL9 gene
      encodes a regulatory myosin MLC and the phosphorylation of this protein is a
      crucial step in the contraction process of smooth muscle cell. Despite the
      absence of human or animal phenotype related to MYL9, a cause-effect relationship
      between MYL9 and the MMIHS seems biologically plausible. The present study
      reveals a strong candidate gene for autosomal recessive forms of MMIHS, expanding
      the molecular basis of this disease and reinforces the myopathic basis of this
      condition.

PMID- 29453417
TI  - Exome sequencing has higher diagnostic yield compared to simulated disease
      specific panels in children with suspected monogenic disorders.
AB  - As test costs decline, whole-exome sequencing (WES) has become increasingly used
      for clinical diagnosis, and now represents the primary alternative to gene panel
      testing for patients with a suspected genetic disorder. We sought to compare the
      diagnostic yield of singleton-WES with simulated application of commercial gene
      panels in children suspected of having a genetically heterogeneous condition.
      Recruitment, singleton-WES and phenotype-driven variant analysis was completed
      for 145 paediatric patients. At recruitment, clinicians were required to propose
      commercial gene panel tests as an alternative to WES and nominate a phenotype
      driven candidate gene list. In WES-diagnosed children, three commercial options
      for each proposed panel were identified and evaluated for hypothetical diagnostic
      yield assuming 100% analytical sensitivity and specificity. We compared the price
      of WES with the least costly panel in WES-diagnosed children. In WES-undiagnosed
      children, we evaluated the exonic coverage of their phenotype-driven gene list
      using aggregate data. WES diagnoses were made in genes not included in at least
      one-of-three commercial panels in 42% of cases. Had a panel been selected
      instead, 23% of WES-diagnosed children would not have been diagnosed. In 26% of
      cases, the least costly panel option would have been more expensive than WES.
      Evaluation of WES coverage found that at the most stringent level of 20*
      coverage, the likelihood of missing a clinically relevant variant in a candidate
      gene list was maximally 8%. The broader coverage of WES makes it a superior
      alternative to gene panel testing at similar financial cost for children with
      suspected complex monogenic phenotypes.

PMID- 29453419
TI  - A randomized controlled study of a consent intervention for participating in an
      NIH genome sequencing study.
AB  - To make an informed choice to participate in a genome sequencing study that may
      yield primary and secondary findings, one understands relevant information in the
      context of personal values. Consent forms to enroll in a sequencing study can be
      long and complex. The efficacy of the professional encounter to consider the
      information contained in the consent form and make an informed choice is unknown.
      Women diagnosed with primary ovarian insufficiency and eligible for a sequencing
      study were randomized to participate in one of two encounters with a genetic
      counselor: a consent intervention using a lower literacy, less dense form or a
      standard consent encounter. Data were complete for 188 of 225 participants. The
      average time was 32 min for the intervention and 34 min for the standard, with
      the intervention encounter generating more questions from participants. At six
      weeks following consent, no differences were found between the two groups in
      primary outcomes: 'sequencing benefits' knowledge (d  =  0.12, 95%CI: 
      0.03,0.27), 'sequencing limitations' knowledge (d  =  0.04, 95%CI: -0.13,0.21),
      expected personal benefits (d  =  -0.01, 95%CI: -0.26,0.23), and decisional
      conflict (d =  0.04, 95%CI: -0.14,0.21). Although intentions to learn secondary
      variants were high, only 60% (113) of participants made an informed choice as
      defined by the multi-dimensional model of informed choice. We found that a
      modified consent intervention was as effective as a standard encounter and led to
      more interaction. Our data suggest that making decisions to receive secondary
      findings may be particularly challenging and in need of further investigation to
      achieve informed choice.

PMID- 29453418
TI  - Periodic reanalysis of whole-genome sequencing data enhances the diagnostic
      advantage over standard clinical genetic testing.
AB  - Whole-genome sequencing (WGS) as a first-tier diagnostic test could transform
      medical genetic assessments, but there are limited data regarding its clinical
      use. We previously showed that WGS could feasibly be deployed as a single
      molecular test capable of a higher diagnostic rate than current practices, in a
      prospectively recruited cohort of 100 children meeting criteria for chromosomal
      microarray analysis. In this study, we report on the added diagnostic yield with
      re-annotation and reanalysis of these WGS data ~2 years later. Explanatory
      variants have been discovered in seven (10.9%) of 64 previously undiagnosed
      cases, in emerging disease genes like HMGA2. No new genetic diagnoses were made
      by any other method in the interval period as part of ongoing clinical care. The
      results increase the cumulative diagnostic yield of WGS in the study cohort to
      41%. This represents a greater than 5-fold increase over the chromosomal
      microarrays, and a greater than 3-fold increase over all the clinical genetic
      testing ordered in practice. These findings highlight periodic reanalysis as yet
      another advantage of genomic sequencing in heterogeneous disorders. We recommend
      reanalysis of an individual's genome-wide sequencing data every 1-2 years until
      diagnosis, or sooner if their phenotype evolves.

PMID- 29453421
TI  - Minimum energy control for complex networks.
AB  - The aim of this paper is to shed light on the problem of controlling a complex
      network with minimal control energy. We show first that the control energy
      depends on the time constant of the modes of the network, and that the closer the
      eigenvalues are to the imaginary axis of the complex plane, the less energy is
      required for complete controllability. In the limit case of networks having all
      purely imaginary eigenvalues (e.g. networks of coupled harmonic oscillators),
      several constructive algorithms for minimum control energy driver node selection
      are developed. A general heuristic principle valid for any directed network is
      also proposed: the overall cost of controlling a network is reduced when the
      controls are concentrated on the nodes with highest ratio of weighted outdegree
      vs indegree.

PMID- 29453420
TI  - A multiplex serologic platform for diagnosis of tick-borne diseases.
AB  - Tick-borne diseases are the most common vector-borne diseases in the United
      States, with serology being the primary method of diagnosis. We developed the
      first multiplex, array-based assay for serodiagnosis of tick-borne diseases
      called the TBD-Serochip. The TBD-Serochip was designed to discriminate antibody
      responses to 8 major tick-borne pathogens present in the United States, including
      Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, Borrelia
      miyamotoi, Ehrlichia chaffeensis, Rickettsia rickettsii, Heartland virus and
      Powassan virus. Each assay contains approximately 170,000 12-mer linear peptides
      that tile along the protein sequence of the major antigens from each agent with
      11 amino acid overlap. This permits accurate identification of a wide range of
      specific immunodominant IgG and IgM epitopes that can then be used to enhance
      diagnostic accuracy and integrate differential diagnosis into a single assay. To
      test the performance of the TBD-Serochip, we examined sera from patients with
      confirmed Lyme disease, babesiosis, anaplasmosis, and Powassan virus disease. We
      identified a wide range of specific discriminatory epitopes that facilitated
      accurate diagnosis of each disease. We also identified previously undiagnosed
      infections. Our results indicate that the TBD-Serochip is a promising tool for a
      differential diagnosis not available with currently employed serologic assays for
      TBDs.

PMID- 29453422
TI  - Operando characterization of cathodic reactions in a liquid-state lithium-oxygen
      micro-battery by scanning transmission electron microscopy.
AB  - Rechargeable non-aqueous lithium-oxygen batteries with a large theoretical
      capacity are emerging as a high-energy electrochemical device for sustainable
      energy strategy. Despite many efforts made to understand the fundamental Li-O2
      electrochemistry, the kinetic process of cathodic reactions, associated with the
      formation and decomposition of a solid Li2O2 phase during charging and
      discharging, remains debate. Here we report direct visualization of the
      charge/discharge reactions on a gold cathode in a non-aqueous lithium-oxygen
      micro-battery using liquid-cell aberration-corrected scanning transmission
      electron microscopy (STEM) combining with synchronized electrochemical
      measurements. The real-time and real-space characterization by time-resolved STEM
      reveals the electrochemical correspondence of discharge/charge overpotentials to
      the nucleation, growth and decomposition of Li2O2 at a constant current density.
      The nano-scale operando observations would enrich our knowledge on the underlying
      reaction mechanisms of lithium-oxygen batteries during round-trip discharging and
      charging and shed lights on the strategies in improving the performances of
      lithium-oxygen batteries by tailoring the cathodic reactions.

PMID- 29453423
TI  - Unexpected mixed-mode transmission and moderate genetic regulation of
      Symbiodinium communities in a brooding coral.
AB  - Determining the extent to which Symbiodinium communities in corals are inherited
      versus environmentally acquired is fundamental to understanding coral resilience
      and to predicting coral responses to stressors like warming oceans that disrupt
      this critical endosymbiosis. We examined the fidelity with which Symbiodinium
      communities in the brooding coral Seriatopora hystrix are vertically transmitted
      and the extent to which communities are genetically regulated, by genotyping the
      symbiont communities within 60 larvae and their parents (9 maternal and 45
      paternal colonies) using high-throughput sequencing of the ITS2 locus.
      Unexpectedly, Symbiodinium communities associated with brooded larvae were
      distinct from those within parent colonies, including the presence of types not
      detected in adults. Bayesian heritability (h2) analysis revealed that 33% of
      variability in larval Symbiodinium communities was genetically controlled.
      Results highlight flexibility in the establishment of larval symbiont communities
      and demonstrate that symbiont transmission is not exclusively vertical in
      brooding corals. Instead, we show that Symbiodinium transmission in S. hystrix
      involves a mixed-mode strategy, similar to many terrestrial invertebrate
      symbioses. Also, variation in the abundances of common Symbiodinium types among
      adult corals suggests that microhabitat differences influence the structure of in
      hospite Symbiodinium communities. Partial genetic regulation coupled with
      flexibility in the environmentally acquired component of Symbiodinium communities
      implies that corals with vertical transmission, like S. hystrix, may be more
      resilient to environmental change than previously thought.

PMID- 29453424
TI  - Genetic control and evolutionary potential of a constitutive resistance mechanism
      against the spruce budworm (Choristoneura fumiferana) in white spruce (Picea
      glauca).
AB  - Insect herbivory may drive evolution by selecting for trees with heritable
      resistance against defoliation. The spruce budworm (Choristoneura fumiferana,
      SBW) is a highly damaging forest insect pest that can affect population structure
      of white spruce (Picea glauca) in North America. Resistance against SBW was
      recently described in white spruce and was linked to three constitutive
      resistance biomarkers: the phenolic compounds piceol and pungenol, and expression
      of a beta-glucosidase encoding gene (Pgbetaglu-1). We investigated the phenotypic
      variability and heritability of these resistance biomarkers and of picein, the
      precursor of piceol, in the foliage of 874 trees belonging to 33 full-sib
      families and 71 clonal lines under evaluation in seven field locations in Eastern
      Canada. We aimed to (i) determine their genetic control, (ii) estimate the
      genetic and phenotypic correlations among defense biomarkers, and (iii) determine
      whether their constitutive levels are associated with detrimental trade-offs on
      growth. Quantitative genetics analyses indicated that all four traits are
      moderately to highly heritable. The full-sib and clonal analyses showed that
      additive and non-additive genetic effects play major and minor roles,
      respectively. Positive genetic and phenotypic correlations between resistance
      biomarkers and primary growth indicated that there is no trade-off between total
      height and height increment and resistance traits, contradicting the GDBH (Growth
      Differentiation Balance Hypothesis). Our findings about the predominant additive
      genetic basis of the resistance biomarkers show that adaptive evolution of white
      spruce natural populations to resist to SBW is possible and that potentially
      important gains could also be expected from artificial selection.

PMID- 29453426
TI  - Importance of embryo aneuploidy screening in preimplantation genetic diagnosis
      for monogenic diseases using the karyomap gene chip.
AB  - We investigated the incidence of aneuploidy in embryos from couples carrying
      monogenic diseases and the effect of embryo aneuploidy screening on the monogenic
      disease preimplantation genetic diagnosis (PGD). From November 2014 to April
      2017, 36 couples carrying monogenic diseases were enrolled. The karyomap gene
      chip technique was used to analyze the blastocysts from the subjects and select
      normal embryos for transfer. A total of 43 single-gene PGD cycles were performed.
      A total of 687 eggs were obtained and 186 blastocysts were biopsed. After
      analysis via karyomap chip, 175 blastocysts received diagnostic results. In our
      monogenic disease PGD, 66.8% (117/175) of the embryos were diagnosed as normal or
      non-pathogenic (silent carriers), and 33.2% (58/175) of the embryos were
      diagnosed as abnormal or pathogenic. For preimplantation genetic screening (PGS),
      the aneuploidy rate of embryos was 22.9% (40/175). Among embryos diagnosed as
      normal for monogenic diseases, 26.5% (31/117) of the embryos were aneuploid and
      could not be transferred. Thus, approximately 1/4 of normal or non-pathogenic
      blastocysts diagnosed based on monogenic disease PGD were aneuploid, indicating
      the necessity and importance of embryo aneuploidy screening during PGD for
      monogenic diseases.

PMID- 29453425
TI  - Chronic treatment with fluoride affects the jejunum: insights from proteomics and
      enteric innervation analysis.
AB  - Gastrointestinal symptoms are the first signs of fluoride (F) toxicity. In the
      present study, the jejunum of rats chronically exposed to F was evaluated by
      proteomics, as well as by morphological analysis. Wistar rats received water
      containing 0, 10 or 50 mgF/L during 30 days. HuC/D, neuronal Nitric Oxide (nNOS),
      Vasoactive Intestinal Peptide (VIP), Calcitonin Gene Related Peptide (CGRP), and
      Substance P (SP) were detected in the myenteric plexus of the jejunum by
      immunofluorescence. The density of nNOS-IR neurons was significantly decreased
      (compared to both control and 10 mgF/L groups), while the VIP-IR varicosities
      were significantly increased (compared to control) in the group treated with the
      highest F concentration. Significant morphological changes were seen observed in
      the density of HUC/D-IR neurons and in the area of SP-IR varicosities for F
      treated groups compared to control. Changes in the abundance of various proteins
      correlated with relevant biological processes, such as protein synthesis, glucose
      homeostasis and energy metabolism were revealed by proteomics.

PMID- 29453427
TI  - Orthodox religious fasting as a medical nutrition therapy for dyslipidemia: where
      do we stand and how far can we go?
AB  - Previous studies have reported inconclusive results regarding the effects of
      Orthodox religious fasting (OF) on common cardiovascular risk factors, including
      arterial hypertension and diabetes. Contrariwise, an optimal effect on
      dyslipidemia has been demonstrated and significant reductions in total
      cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) concentrations,
      in Orthodox populations without comorbidities, have been consistently reported.
      This favorable effect on lipid homeostasis is probably facilitated by a broad
      lifestyle modification related to OF, extended beyond dietary habits. However,
      several clinical issues require further clarification by future trials including
      the efficacy and safety of OF in specific groups of patients with dyslipidemia,
      mainly those with cardiovascular disease and diabetes, the effects of OF on high
      density lipoprotein-cholesterol (HDL-C), the dietary limitations of specific
      vitamins and minerals during fasting, as well as the optimal duration of this
      dietary intervention. The present article aims to discuss, whether there is a
      strong enough theoretical background, to currently support the implementation of
      OF as a medical nutrition therapy for dyslipidemia in the daily clinical setting,
      with a discourse on available evidence and future research agenda.

PMID- 29453428
TI  - IGF-I and IGFBP-3 concentrations at 2 years: associations with anthropometry and
      milk consumption in an Indian cohort.
AB  - BACKGROUND/OBJECTIVES: To ascertain associations between plasma insulin-like
      growth factor I (IGF-I), insulin-like growth factor-binding protein 3 (IGFBP-3)
      and their molar ratio at 2 y with neonatal size, infant growth, body composition
      at 2 y, and feeding practices in an Indian cohort. SUBJECTS/METHODS: A cohort of
      209 newborns, with 122 followed at 2 y. Anthropometry was conducted at birth and
      2 y. IGF-I and IGFBP-3 concentrations were measured in cord blood and at 2 y.
      Maternal and child diet was assessed by food frequency questionnaires and
      maternal interviews. Multivariate regression was used to test for associations
      adjusting for confounding factors. RESULTS: Mean 2 y plasma IGF-I and IGFBP-3
      concentrations and IGF-I/IGFBP-3 were 49.4 ng/ml (95% CI: 44.1, 54.8), 1953.8
      ng/ml (CI: 1870.6, 2036.9) ng/ml, and 0.088 (CI: 0.081, 0.095), respectively. IGF
      I and IGF-I/IGFBP-3 were positively associated with current length, but not body
      mass index or adiposity. IGF-I was higher among those with greater change in
      length since birth. IGF-I concentrations were higher in children who drank the
      most milk (>500 vs. <250 ml per day: 65.6 vs. 42.8 ng/ml, p < 0.04), received
      other milk <6 months compared to >=6 months (56.3 vs. 44.8 ng/ml, p < 0.05), and
      in those whose mothers consumed milk daily vs. less frequently in late pregnancy
      (56.4 vs. 42.7 ng/ml, p < 0.01). In multivariate regression, 2 y IGF-I
      concentration and IGF-I/IGFBP-3 were each positively associated with current
      length and milk intake. IGFBP-3 was not related to anthropometry or milk intake.
      CONCLUSIONS: Plasma IGF-I concentrations and IGF-I/IGFBP-3 at 2 y are positively
      associated with length at 2 y and current milk intake.

PMID- 29453429
TI  - Human neutrophils can mimic myeloid-derived suppressor cells (PMN-MDSC) and
      suppress microbead or lectin-induced T cell proliferation through artefactual
      mechanisms.
AB  - We report that human conventional CD15+ neutrophils can be isolated in the
      peripheral blood mononuclear cell (PBMC) layer during Ficoll gradient separation,
      and that they can impair T cell proliferation in vitro without concomitant
      neutrophil activation and killing. This effect was observed in a total of 92
      patients with organ transplants, lung cancer or anxiety/depression, and in 18
      healthy donors. Although such features are typically associated in the literature
      with the presence of certain myeloid-derived suppressor cell (PMN-MDSC)
      populations, we found that commercial centrifuge tubes that contained membranes
      or gels for PBMC isolation led to up to 70% PBMC contamination by CD15+
      neutrophils, with subsequent suppressive effects in certain cellular assays. In
      particular, the suppressive activity of human MDSC should not be evaluated using
      lectin or microbead stimulation, whereas assays involving soluble or plate-bound
      antibodies or MLR are unaffected. We conclude that CD15+ neutrophil
      contamination, and associated effects on suppressor assays, can lead to
      significant artefacts in studies of human PMN-MDSC.

PMID- 29453430
TI  - Increased deficit of visual attention span with development in Chinese children
      with developmental dyslexia.
AB  - It has been suggested that orthographic transparency and age changes may affect
      the relationship between visual attention span (VAS) deficit and reading
      difficulty. The present study explored the developmental trend of VAS in children
      with developmental dyslexia (DD) in Chinese, a logographic language with a deep
      orthography. Fifty-seven Chinese children with DD and fifty-four age-matched
      normal readers participated. The visual 1-back task was adopted to examine VAS.
      Phonological and morphological awareness tests, and reading tests in single
      character and sentence levels were used for reading skill measurements. Results
      showed that only high graders with dyslexia exhibited lower accuracy than the
      controls in the VAS task, revealing an increased VAS deficit with development in
      the dyslexics. Moreover, the developmental trajectory analyses demonstrated that
      the dyslexics seemed to exhibit an atypical but not delayed pattern in their VAS
      development as compared to the controls. A correlation analysis indicated that
      VAS was only associated with morphological awareness for dyslexic readers in high
      grades. Further regression analysis showed that VAS skills and morphological
      awareness made separate and significant contributions to single-character reading
      for high grader with dyslexia. These findings suggested a developmental
      increasing trend in the relationship between VAS skills and reading (dis)ability
      in Chinese.

PMID- 29453431
TI  - Delayed gut microbiota development in high-risk for asthma infants is temporarily
      modifiable by Lactobacillus supplementation.
AB  - Gut microbiota dysbiosis and metabolic dysfunction in infancy precedes childhood
      atopy and asthma development. Here we examined gut microbiota maturation over the
      first year of life in infants at high risk for asthma (HR), and whether it is
      modifiable by early-life Lactobacillus supplementation. We performed a
      longitudinal comparison of stool samples collected from HR infants randomized to
      daily oral Lactobacillus rhamnosus GG (HRLGG) or placebo (HRP) for 6 months, and
      healthy (HC) infants. Meconium microbiota of HRP participants is distinct,
      follows a delayed developmental trajectory, and is primarily glycolytic and
      depleted of a range of anti-inflammatory lipids at 6 months of age. These
      deficits are partly rescued in HRLGG infants, but this effect was lost at 12
      months of age, 6 months after cessation of supplementation. Thus we show that
      early-life gut microbial development is distinct, but plastic, in HR infants. Our
      findings offer a novel strategy for early-life preventative interventions.

PMID- 29453432
TI  - Validation of house-keeping genes for normalization of gene expression data
      during diurnal/circadian studies in rice by RT-qPCR.
AB  - The circadian clock in plants is the intrinsic rhythmic expression of thousands
      of genes in a 24 h period, which is set by the day-night cycles in the
      environment. The study of the circadian clock often requires expression profiling
      of genes over a large number of samples for which RT-qPCR is invariably used.
      Reliability of the results depends largely on the house-keeping genes, which
      serve as control and thus should be chosen carefully to prevent erroneous
      results. In this study, ten house-keeping genes were chosen from rice for
      stability analysis with 48 tissue samples harvested from plants subjected to
      diurnal/circadian cycles. Although, all the genes were found to be stable,
      however, six of them showed cyclic expression patterns and caused major changes
      in the expression profiles of the target genes when used to normalize their
      expression data, thereby making them poor candidates for diurnal/circadian
      studies. In conclusion, reference genes need to be selected for diurnal/circadian
      studies with extra caution as more than 80% of transcriptome in plants undergoes
      cycling, which remains undetected by the gene stability assessment software and
      can severely affect the RT-qPCR based gene expression profiling. The geometric
      mean of two or more most stable reference genes is hence recommended for
      diurnal/circadian studies in plants.

PMID- 29453433
TI  - Randomized trial of earlier versus later oral feeding in very premature infants.
AB  - OBJECTIVES: To ascertain if earlier oral feeding initiation results in earlier
      attainment of full oral feedings/hospital discharge in very premature infants.
      STUDY DESIGN: Eligible infants born at <29 weeks' gestation were randomized at 30
      weeks' postmenstrual age (PMA) to initiate oral feedings at 30 weeks' PMA
      (Earlier Oral Feeding Group) versus 33 weeks' PMA (Later Oral Feeding Group).
      RESULTS: Thirty-four infants were randomized to the Earlier Oral Feeding Group
      and 32 to the Later Oral Feeding Group. There were no significant differences in
      our primary outcomes of PMA at full oral feedings (mean difference -0.5 weeks,
      95% CI: -2.2 to +1.2 weeks) or hospital discharge (mean difference -0.2 weeks,
      95% CI: -1.8 to +1.4 weeks). CONCLUSIONS: Initiating oral feeding attempts in
      very premature infants at 30 weeks' PMA does not result in earlier attainment of
      full oral feedings or discharge but is safe for infants who are not severely
      tachypneic or receiving positive pressure.

PMID- 29453434
TI  - Post-ligation cardiac syndrome is associated with increased morbidity in preterm
      infants.
AB  - OBJECTIVE: The influence of post-ligation cardiac syndrome (PLCS), a complication
      of patent ductus arteriosus (PDA) ligations, on neonatal outcomes is unknown. The
      purpose of this study was to determine the risks of PLCS on severe pulmonary
      morbidity and severe retinopathy of prematurity (ROP). STUDY DESIGN:
      Retrospective cohort study of infants who underwent a PDA ligation between 2006
      and 2015. Data were collected on patients with and without PLCS. The primary
      outcome was the difference in severe bronchopulmonary dysplasia (BPD) between
      groups. Secondary outcomes included discharge with home oxygen and severe ROP.
      RESULT: A total of 100 infants that underwent PDA ligation during the study
      period were included in the study; 31 (31%) neonates developed PLCS. In adjusted
      analysis, PLCS was associated with increased risk for severe BPD (RR 1.67, 95%
      CI: 1.15-2.42) and home oxygen therapy (RR: 1.47, 95% CI: 1.09-1.99) only. No
      association with severe ROP was seen (RR: 1.48; 95% CI: 0.87-2.52). CONCLUSION:
      PLCS is associated with severe neonatal pulmonary morbidity, but not with severe
      ROP. Further investigation is warranted to validate these results.

PMID- 29453435
TI  - Evidence of a gene-environment interaction of NODAL variants and inflammation in
      preterm birth.
AB  - OBJECTIVE: NODAL has been implicated in timing of parturition and immune
      regulation. We investigated the relationship between NODAL polymorphisms,
      infection/inflammation, and preterm birth. STUDY DESIGN: For this secondary
      analysis, 613 women (189 preterm and 424 term) from the Montreal Prematurity
      Study were genotyped for NODAL polymorphisms and assessed for bacterial vaginosis
      and placental inflammation. RESULT: NODAL polymorphisms were not associated with
      preterm birth. However, the rs2231947(C>T) variant allele was associated with
      increased risk for preterm birth among women with bacterial vaginosis (odds
      ratio: 2.76, 95% confidence interval: 1.12-6.85). Among women without placental
      inflammation, the rs1904589(A>G) variant allele was associated with increased
      risk of preterm birth (odds ratio: 1.31, 95% confidence interval: 1.02-1.70).
      Among women with placental inflammation, the rs10999338(C>T) variant allele was
      associated with reduced risk of preterm birth (odds ratio: 0.50, 95% confidence
      interval: 0.29-0.87). CONCLUSION: The effect of NODAL polymorphisms on preterm
      birth depends on maternal infection/inflammation status.

PMID- 29453436
TI  - Rural-urban differences in access to hospital obstetric and neonatal care: how
      far is the closest one?
AB  - OBJECTIVES: To quantify drive distances to hospital obstetric services and
      advanced neonatal care and to examine such disparities by residential rurality
      and insurance type. STUDY DESIGN: Data for all-payer maternal childbirth
      hospitalizations in 2002 (N = 661,240) and 2013 (N = 634,807) from nine
      geographically dispersed states were linked with the American Hospital
      Association annual surveys to identify maternal residence zip codes and the
      addresses of hospitals with obstetric services or advanced neonatal care.
      RESULTS: The uneven geographic distribution of hospital obstetric and advanced
      neonatal care increased between 2002 and 2013, varying by maternal residential
      rurality and insurance type. Women in rural non-core areas, with Medicaid or no
      insurance, and living in counties with lower income and educational attainment,
      had to travel farther to the nearest hospital with obstetric services or neonatal
      care than their counterparts. CONCLUSIONS: Women in communities that are already
      socioeconomically disadvantaged face increasing and substantial travel distances
      to access perinatal care.

PMID- 29453437
TI  - Enhancement of immunomodulative effect of lactic acid bacteria on plasmacytoid
      dendritic cells with sucrose palmitate.
AB  - Plasmacytoid dendritic cells (pDCs) play a key role in the immune response
      against viruses. In addition, recent research has suggested that pDCs possess
      direct and indirect tumoricidal activities. We previously found that a lactic
      acid bacteria strain, Lactococcus lactis JCM 5805 (LC-Plasma), stimulated pDCs
      and prevented viral infection in mouse and human studies. Meanwhile, emulsifiers
      have recently been highlighted as candidate adjuvants for some viral vaccines and
      cancer immunotherapies. In this study, we discovered some specific emulsifiers,
      mainly consisting of sucrose fatty acid esters, that drastically enhance the
      potency of LC-Plasma to activate pDCs in vitro. The emulsifiers promoted the
      efficient uptake of LC-Plasma by pDCs and the ratio of pDCs that took up LC
      Plasma correlated with the activity of pDCs. In addition, an in vivo study showed
      that oral treatment with LC-Plasma mixed with an emulsifier induced a higher
      expression of genes related to anti-viral immunity in the lung compared to
      treatment with LC-Plasma alone. Both LC-Plasma and the emulsifiers used in this
      study have been confirmed to be safe for human use. Therefore, LC-Plasma mixed
      with an emulsifier might be a useful tool for certain anti-cancer and anti-viral
      therapies.

PMID- 29453438
TI  - Altered immunity in crowded Mythimna separata is mediated by octopamine and
      dopamine.
AB  - Similar to pathogenic infection, high population density alters insects'
      prophylactic immunity. Density-dependent prophylaxis has been reported in many
      polyphenic insects, but the regulatory mechanism underlying this phenomenon
      remains unclear. The biogenic monoamines are known to play critical roles in
      mediating insect immune responses. In the current study, the immune capacity and
      the levels of three biogenic monoamines were investigated in the polyphenic
      larvae of Mythimna separata, reared at the densities of 1, 2, 5, 10, and 30
      larvae per 650-mL jar. Concomitant with the increased phenoloxidase (PO) activity
      and total haemocyte count in the larvae at high densities (5, 10, 30 larvae/jar),
      the octopamine level was also increased. In contrast, the dopamine level was
      decreased, and the 5-hydroxytryptamine level was not significantly affected.
      Injection of octopamine induced significant increases in the total haemocyte
      count and PO activity. Conversely, epinastine, a specific antagonist of
      octopamine, decreased the total haemocyte count and PO activity. Another
      octopamine antagonist, phentolamine, inhibited the activity of PO and lysozymes.
      In addition, injection of dopamine induced a significant increase in PO activity
      and decreased the total haemocyte count and lysozyme activity. These results
      suggested that both octopamine and dopamine mediate the increases in total
      haemocyte count and PO activity in the crowded larvae.

PMID- 29453440
TI  - Allocation of photosynthesized carbon in an intensively farmed winter wheat-soil
      system as revealed by 14CO2 pulse labelling.
AB  - Understanding the rhizodeposited carbon (C) dynamics of winter wheat (Triticum
      aestivum L.), is crucial for soil fertility and C sequestration. Pot-grown winter
      wheat was pulse labelled with 14CO2 at the key growth stages. 14C in the shoots,
      roots and soil was measured at 5 or 2 days after 14C-labelling (DAL 5/2) at each
      growth stage and at harvest. The 14C in the shoots increased from 4% of the net
      14C recovered (shoots + roots + soil) during tillering to 53% at harvest.
      Approximately 14-34% of the net 14C recovered was incorporated into the soil.
      Allocation of photosynthesized C was extrapolated from the pot experiment to
      field condition, assuming a planting density of 1.8 million plants ha-1. The
      estimated C input to the soil was 1.7 t C ha-1, and 0.7 t C ha-1 of root residues
      was retained after wheat harvest; both values were higher than those previously
      reported (0.6 and 0.4 t C ha-1, respectively). Our findings highlight that C
      tracing during the entire crop season is necessary to quantify the temporal
      allocation of photosynthesized C, especially the contribution to soil carbon in
      intensified farming system.

PMID- 29453439
TI  - Working Memory And Brain Tissue Microstructure: White Matter Tract Integrity
      Based On Multi-Shell Diffusion MRI.
AB  - Working memory is a complex cognitive process at the intersection of sensory
      processing, learning, and short-term memory and also has a general executive
      attention component. Impaired working memory is associated with a range of
      neurological and psychiatric disorders, but very little is known about how
      working memory relates to underlying white matter (WM) microstructure. In this
      study, we investigate the association between WM microstructure and performance
      on working memory tasks in healthy adults (right-handed, native English
      speakers). We combine compartment specific WM tract integrity (WMTI) metrics
      derived from multi-shell diffusion MRI as well as diffusion tensor/kurtosis
      imaging (DTI/DKI) metrics with Wechsler Adult Intelligence Scale-Fourth Edition
      (WAIS-IV) subtests tapping auditory working memory. WMTI is a novel tool that
      helps us describe the microstructural characteristics in both the intra- and
      extra-axonal environments of WM such as axonal water fraction (AWF), intra-axonal
      diffusivity, extra-axonal axial and radial diffusivities, allowing a more
      biophysical interpretation of WM changes. We demonstrate significant positive
      correlations between AWF and letter-number sequencing (LNS), suggesting that
      higher AWF with better performance on complex, more demanding auditory working
      memory tasks goes along with greater axonal volume and greater myelination in
      specific regions, causing efficient and faster information process.

PMID- 29453441
TI  - Circulating cell-free mitochondrial DNA, but not leukocyte mitochondrial DNA copy
      number, is elevated in major depressive disorder.
AB  - Major depressive disorder (MDD) has been linked to mitochondrial defects, which
      could manifest in mitochondrial DNA (mtDNA) polymorphisms or mutations.
      Additionally, copy number of mtDNA (mtDNA-cn) can be quantified in peripheral
      blood mononuclear cells (PBMC)s, indirectly reflecting cellular energetics, or in
      the circulating cell-free mtDNA (ccf-mtDNA) levels, which may reflect a fraction
      of the mitochondrial genome released during cellular stress. Few studies have
      examined ccf-mtDNA in MDD, and no studies have tested its relationship with
      intracellular mtDNA-cn or with antidepressant treatment response. Here, mtDNA
      levels were quantified in parallel from: (i) PBMCs and (ii) cell-free plasma of
      50 unmedicated MDD subjects and 55 controls, in parallel with PBMC telomere
      length (TL) and antioxidant enzyme glutathione peroxidase (GpX) activity. MtDNA
      measures were repeated in 19 MDD subjects after 8 weeks of open-label SSRI
      treatment. In analyses adjusted for age, sex, BMI, and smoking, MDD subjects had
      significantly elevated levels of ccf-mtDNA (F = 20.6, p = 0.00002). PBMC mtDNA-cn
      did not differ between groups (p > 0.4). In preliminary analyses, we found that
      changes in ccf-mtDNA with SSRI treatment differed between SSRI responders and non
      responders (F = 6.47, p = 0.02), with the non-responders showing an increase in
      ccf-mtDNA and responders not changing. Baseline ccf-mtDNA was positively
      correlated with GpX (r = 0.32, p = 0.001), and PBMC mtDNA correlated positively
      with PBMC TL (r = 0.38, p = 0.0001). These data suggest that plasma ccf-mtDNA and
      PBMC mtDNA-cn reflect different cellular processes and that the former may be
      more reflective of certain aspects of MDD pathophysiology and of the response to
      SSRI antidepressants.

PMID- 29453442
TI  - White matter integrity in medication-free women with peripartum depression: a
      tract-based spatial statistics study.
AB  - Diffusion tensor imaging (DTI) studies in depression show decreased structural
      connectivity in the left anterior limb of the internal capsule and the genu of
      the corpus callosum but no such studies exist in peripartum depression (PPD),
      which affects 1 in 8 women. We analyzed fractional anisotropy (FA) as a measure
      of white matter integrity of these two tracts using tract-based spatial
      statistics (TBSS). We then conducted an exploratory whole-brain analysis to
      identify additional regions implicated in PPD. Seventy-five pregnant, medication
      free women were evaluated with the Edinburgh Postnatal Depression Scale (EPDS)
      and Structured Clinical Interview (SCID) for DSM-IV-TR in pregnancy and in the
      postpartum. Structural MRI and DTI sequences were acquired in forty-four women
      within 2-8 weeks postpartum. TBSS data were analyzed between healthy comparison
      postpartum women (HCW) and women who developed PPD to determine differences in
      white matter integrity within the left anterior limb of the internal capsule and
      the genu of the corpus callosum, then analyzed across participants to explore
      correlation between FA and the EPDS score. An exploratory whole-brain analysis
      was also conducted to identify other potential regions showing differences in
      white matter integrity between groups, as well as correlation between EPDS and FA
      across groups. All results were corrected for multiple comparisons and analyses
      conducted using FSL, p < 0.05, K > 10. In comparison to HCW, women with PPD had
      significantly lower FA in left anterior limb of the internal capsule (p = 0.010).
      FA was negatively correlated with EPDS scores in the left anterior limb of the
      internal capsule (p = 0.019). In the whole-brain analysis, FA in the right
      retrolenticular internal capsule (p = 0.03) and two clusters within the body of
      the corpus callosum (p = 0.044, p = 0.050) were negatively correlated with EPDS;
      there were no between-group differences in FA. Reduced FA in the left anterior
      limb of the internal capsule suggests disruption of fronto-subcortical circuits
      in PPD. A negative correlation between FA within the body of the corpus callosum
      and EPDS total score could additionally reflect disrupted interhemispheric
      structural connectivity in women with depressive symptoms.

PMID- 29453443
TI  - Role of the mesolimbic dopamine system in relief learning.
AB  - The relief from an aversive event is rewarding. Since organisms are able to learn
      which environmental cues can cease an aversive event, relief learning helps to
      better cope with future aversive events. Literature data suggest that relief
      learning is affected in various psychopathological conditions, such as anxiety
      disorders. Here, we investigated the role of the mesolimbic dopamine system in
      relief learning. Using a relief learning procedure in Sprague Dawley rats, we
      applied a combination of behavioral experiments with anatomical tracing, c-Fos
      immunohistochemistry, and local chemogenetic and pharmacological interventions to
      broadly characterize the role of the mesolimbic dopamine system. The present
      study shows that a specific part of the mesolimbic dopamine system, the
      projection from the posterior medial ventral tegmental area (pmVTA) to the
      nucleus accumbens shell (AcbSh), is activated by aversive electric stimuli. 6
      OHDA lesions of the pmVTA blocked relief learning but fear learning and safety
      learning were not affected. Chemogenetic silencing of the pmVTA-AcbSh projection
      using the DREADD approach, as well as intra-AcbSh injections of the dopamine D2/3
      receptor antagonist raclopride inhibited relief learning. Taken together, the
      present data demonstrate that the dopaminergic pmVTA-AcbSh projection is critical
      for relief learning but not for similar learning phenomena. This novel finding
      may have clinical implications since the processing of signals predicting relief
      and safety is often impaired in patients suffering from anxiety disorders.
      Furthermore, it may help to better understand psychological conditions like non
      suicidal self-injury, which are associated with pain offset relief.

PMID- 29453444
TI  - Positive regulation of raphe serotonin neurons by serotonin 2B receptors.
AB  - Serotonin is a neurotransmitter involved in many psychiatric diseases. In humans,
      a lack of 5-HT2B receptors is associated with serotonin-dependent phenotypes,
      including impulsivity and suicidality. A lack of 5-HT2B receptors in mice
      eliminates the effects of molecules that directly target serotonergic neurons
      including amphetamine derivative serotonin releasers, and selective serotonin
      reuptake inhibitor antidepressants. In this work, we tested the hypothesis that 5
      HT2B receptors directly and positively regulate raphe serotonin neuron activity.
      By ex vivo electrophysiological recordings, we report that stimulation by the 5
      HT2B receptor agonist, BW723C86, increased the firing frequency of serotonin Pet1
      positive neurons. Viral overexpression of 5-HT2B receptors in these neurons
      increased their excitability. Furthermore, in vivo 5-HT2B-receptor stimulation by
      BW723C86 counteracted 5-HT1A autoreceptor-dependent reduction in firing rate and
      hypothermic response in wild-type mice. By a conditional genetic ablation that
      eliminates 5-HT2B receptor expression specifically and exclusively from Pet1
      positive serotonin neurons (Htr2b 5-HTKO mice), we demonstrated that behavioral
      and sensitizing effects of MDMA (3,4-methylenedioxy-methamphetamine), as well as
      acute behavioral and chronic neurogenic effects of the antidepressant fluoxetine,
      require 5-HT2B receptor expression in serotonergic neurons. In Htr2b 5-HTKO mice,
      dorsal raphe serotonin neurons displayed a lower firing frequency compared to
      control Htr2b lox/lox mice as assessed by in vivo extracellular recordings and a
      stronger hypothermic effect of 5-HT1A-autoreceptor stimulation was observed. The
      increase in head-twitch response to DOI (2,5-dimethoxy-4-iodoamphetamine) further
      confirmed the lower serotonergic tone resulting from the absence of 5-HT2B
      receptors in serotonin neurons. Together, these observations indicate that the 5
      HT2B receptor acts as a direct positive modulator of serotonin Pet1-positive
      neurons in an opposite way as the known 5-HT1A-negative autoreceptor.

PMID- 29453445
TI  - Alterations in interhemispheric gamma-band connectivity are related to the
      emergence of auditory verbal hallucinations in healthy subjects during NMDA
      receptor blockade.
AB  - Auditory verbal hallucinations (AVH) are a common positive symptom of
      schizophrenia. Excitatory-to-inhibitory (E/I) imbalance related to disturbed N
      methyl-D-aspartate receptor (NMDAR) functioning has been suggested as a possible
      mechanism underlying altered connectivity and AVH in schizophrenia. The current
      study examined the effects of ketamine, a NMDAR antagonist, on glutamate-related
      mechanisms underlying interhemispheric gamma-band connectivity, conscious
      auditory perception during dichotic listening (DL), and the emergence of auditory
      verbal distortions and hallucinations (AVD/AVH) in healthy volunteers. In a
      single-blind, pseudo-randomized, placebo-controlled crossover design, nineteen
      male, right-handed volunteers were measured using 64 channel
      electroencephalography (EEG). Psychopathology was assessed with the PANSS
      interview and the 5D-ASC questionnaire, including a subscale to detect auditory
      alterations with regard to AVD/AVH (AUA-AVD/AVH). Interhemispheric connectivity
      analysis was performed using eLORETA source estimation and lagged phase
      synchronization (LPS) in the gamma-band range (30-100 Hz). Ketamine induced
      positive symptoms such as hallucinations in a subgroup of healthy subjects. In
      addition, interhemispheric gamma-band connectivity was found to be altered under
      ketamine compared to placebo, and subjects with AUA-AVD/AVH under ketamine showed
      significantly higher interhemispheric gamma-band connectivity than subjects
      without AUA-AVD/AVH. These findings demonstrate a relationship between NMDAR
      functioning, interhemispheric connectivity in the gamma-band frequency range
      between bilateral auditory cortices and the emergence of AVD/AVH in healthy
      subjects. The result is in accordance with the interhemispheric miscommunication
      hypothesis of AVH and argues for a possible role of glutamate in AVH in
      schizophrenia.

PMID- 29453446
TI  - Environmental, genetic and epigenetic contributions to cocaine addiction.
AB  - Decades of research on cocaine has produced volumes of data that have answered
      many important questions about the nature of this highly addictive drug. Sadly,
      none of this information has translated into the development of effective
      therapies for the treatment of cocaine addiction. This review endeavors to assess
      the current state of cocaine research in an attempt to identify novel pathways
      for therapeutic development. For example, risk of cocaine addiction is highly
      heritable but genome-wide analyses comparing cocaine-dependent individuals to
      controls have not resulted in promising targets for drug development. Is this
      because the genetics of addiction is too complex or because the existing research
      methodologies are inadequate? Likewise, animal studies have revealed dozens of
      enduring changes in gene expression following prolonged exposure to cocaine, none
      of which have translated into therapeutics either because the resulting compounds
      were ineffective or produced intolerable side-effects. Recently, attention has
      focused on epigenetic modifications resulting from repeated cocaine intake, some
      of which appear to be heritable through changes in the germline. While epigenetic
      changes represent new vistas for therapeutic development, selective manipulation
      of epigenetic marks is currently challenging even in animals such that
      translational potential is a distant prospect. This review will reveal that
      despite the enormous progress made in understanding the molecular and
      physiological bases of cocaine addiction, there is much that remains a mystery.
      Continued advances in genetics and molecular biology hold potential for revealing
      multiple pathways toward the development of treatments for the continuing scourge
      of cocaine addiction.

PMID- 29453448
TI  - The gastrointestinal tract microbiota of northern white-cheeked gibbons (Nomascus
      leucogenys) varies with age and captive condition.
AB  - Nutrition and health of northern white-cheeked gibbons (Nomascus leucogenys) are
      considered to be primarily influenced by the diversity of their gastrointestinal
      tract (GIT) microbiota. However, the precise composition, structure, and role of
      the gibbon GIT microbiota remain unclear. Microbial communities from the GITs of
      gibbons from Nanning (NN, n = 36) and Beijing (BJ, n = 20) Zoos were examined
      through 16S rRNA sequencing. Gibbon's GITs microbiomes contained bacteria from 30
      phyla, dominated by human-associated microbial signatures: Firmicutes,
      Bacteroidetes, and Proteobacteria. Microbial species richness was markedly
      different between adult gibbons (>8 years) under distinct captive conditions. The
      relative abundance of 14 phyla varied significantly in samples of adults in BJ
      versus NN. Among the age groups examined in NN, microbiota of adult gibbons had
      greater species variation and richer community diversity than microbiota of
      nursing young (<6 months) and juveniles (2-5 years). Age-dependent increases in
      the relative abundances of Firmicutes and Fibrobacteres were detected, along with
      simultaneous increases in dietary fiber intake. A few differences were detected
      between sex cohorts in NN, suggesting a very weak correlation between sex and GIT
      microbiota. This study is the first to taxonomically identify gibbon's GITs
      microbiota confirming that microbiota composition varies with age and captive
      condition.

PMID- 29453447
TI  - Embryonic stem cell transplants as a therapeutic strategy in a rodent model of
      autism.
AB  - Autism is a neurodevelopmental disorder characterized by disruptions in three
      core behavioral domains: deficits in social interaction, impairments in
      communication, and repetitive and stereotyped patterns of behavior or thought.
      There are currently no drugs available for the treatment of the core symptoms of
      ASD and drugs that target comorbid symptoms often have serious adverse side
      effects, suggesting an urgent need for new therapeutic strategies. The
      neurobiology of autism is complex, but converging evidence suggests that ASD
      involves disruptions in the inhibitory GABAergic neurotransmitter system.
      Specifically, people with autism have a reduction in parvalbumin (PV)-containing
      interneurons in the PFC, leading to the suggestion that restoring interneuron
      function in this region may be a novel therapeutic approach for ASD. Here we used
      a dual-reporter embryonic stem cell line to generate enriched populations of PV
      positive interneurons, which were transplanted into the medial prefrontal cortex
      (mPFC) of the Poly I:C rodent model of autism. PV interneuron transplants were
      able to decrease pyramidal cell firing in the mPFC and alleviated deficits in
      social interaction and cognitive flexibility. Our results suggest that restoring
      PV interneuron function in the mPFC may be a novel and effective treatment
      strategy to reduce the core symptoms of autism.

PMID- 29453449
TI  - Functional analysis of SLC39A8 mutations and their implications for manganese
      deficiency and mitochondrial disorders.
AB  - SLC39A8 encodes ZIP8, a divalent metal ion transporter. Mutations in the SLC39A8
      gene are associated with congenital disorder of glycosylation type II and Leigh
      syndrome. Notably, affected patients with both disorders exhibited severe
      manganese (Mn) deficiency. The cellular function of human SLC39A8 (hSLC39A8) and
      the mechanisms by which mutations in this protein lead to human diseases are
      unclear. Herein, we show that hSLC39A8 mediates 54Mn uptake by the cells, and its
      expression is regulated by Mn. While expression of wild-type hSLC39A8 increased
      54Mn uptake activity, disease-associated mutations abrogated the ability of the
      transporter to mediate Mn uptake into the cells, thereby providing a causal link
      to severe Mn deficiency. All mutants failed to localize on the cell surface and
      were retained within the endoplasmic reticulum. Interestingly, expression of
      hSLC39A8 mutants of both CDG type II and Leigh syndrome reduced mitochondrial
      54Mn levels and activity of Mn-dependent mitochondrial superoxide dismutase
      MnSOD, and in turn increased oxidative stress. The expression of wild-type
      hSLC39A8, but not the disease-associated mutants, promoted mitochondrial
      functions. Moreover, loss of function analyses further corroborate hSLC39A8's
      critical role in mediating Mn uptake and mitochondrial function. Our results
      provide a potential pathogenic mechanism of diseases that are associated with
      hSLC39A8 mutations.

PMID- 29453450
TI  - Insights into the inhibitory mechanisms of NADH on the alphagamma heterodimer of
      human NAD-dependent isocitrate dehydrogenase.
AB  - Human NAD-dependent isocitrate dehydrogenase (NAD-IDH) catalyzes the oxidative
      decarboxylation of isocitrate in the citric acid cycle. In the alpha2betagamma
      heterotetramer of NAD-IDH, the gamma subunit plays the regulatory role and the
      beta subunit the structural role. Previous biochemical data have shown that
      mammalian NAD-IDHs can be inhibited by NADH; however, the molecular mechanism is
      unclear. In this work, we show that the alphabeta, alphagamma and alpha2betagamma
      enzymes of human NAD-IDH can be inhibited by NADH, and further determine the
      crystal structure of the alphagamma heterodimer bound with an Mg2+ and an NADH at
      the active site and an NADH at the allosteric site, which resembles that of the
      inactive alphaMggamma heterodimer. The NADH at the active site occupies the
      binding site for NAD+ and prevents the binding of the cofactor. The NADH at the
      allosteric site occupies the binding sites for ADP and citrate and blocks the
      binding of the activators. The biochemical data confirm that the NADH binding
      competes with the binding of NAD+ and the binding of citrate and ADP, and the two
      effects together contribute to the NADH inhibition on the activity. These
      findings provide insights into the inhibitory mechanisms of the alphagamma
      heterodimer by NADH.

PMID- 29453451
TI  - Prevalence and impact of baseline resistance-associated substitutions on the
      efficacy of ledipasvir/sofosbuvir or simeprevir/sofosbuvir against GT1 HCV
      infection.
AB  - Baseline resistance-associated substitutions (RASs) have variable impacts in
      clinical trials but their prevalence and impact in real-world patients remains
      unclear. We performed baseline resistance testing using a commercial assay (10%
      cutoff) for 486 patients treated with LDV/SOF or SMV/SOF, with or without
      ribavirin, in the multi-center, observational HCV-TARGET cohort. Linkage of RASs
      was evaluated in selected samples using a novel quantitative single variant
      sequencing assay. Our results showed that the prevalence of NS3, NS5A, NS5B RASs
      was 45%, 13%, and 8%, respectively, and 10% of patients harbored RASs in 2 or
      more drug classes. Baseline LDV RASs in GT1a, TE, and cirrhosis LDV/SOF subgroup
      was associated with 2-4% lower SVR12 rates. SMV RASs was associated with lower
      SVR12 rates in GT1a, treatment-experienced, cirrhotics SMV/SOF subgroup. Pooled
      analysis of all patients with baseline RASs revealed that SVR12 was 100% (19/19)
      in patients treated for longer than 98 days but was 87% (81/93) in patients
      treated for shorter than 98 days. These results demonstrate that RASs prevalence
      and their impact in real world practice are in general agreement with
      registration trials, and suggest that longer treatment duration may overcome the
      negative impact of baseline RASs on SVR12 rates in clinical practice.

PMID- 29453453
TI  - A Meta-Surface Antenna Array Decoupling (MAAD) Method for Mutual Coupling
      Reduction in a MIMO Antenna System.
AB  - In this paper, a method to reduce the inevitable mutual coupling between antennas
      in an extremely closely spaced two-element MIMO antenna array is proposed. A
      suspended meta-surface composed periodic square split ring resonators (SRRs) is
      placed above the antenna array for decoupling. The meta-surface is equivalent to
      a negative permeability medium, along which wave propagation is rejected. By
      properly designing the rejection frequency band of the SRR unit, the mutual
      coupling between the antenna elements in the MIMO antenna system can be
      significantly reduced. Two prototypes of microstrip antenna arrays at 5.8 GHz
      band with and without the metasurface have been fabricated and measured. The
      matching bandwidths of antennas with reflection coefficient smaller than -15 dB
      for the arrays without and with the metasurface are 360 MHz and 900 MHz
      respectively. Using the meta-surface, the isolation between elements is increased
      from around 8 dB to more than 27 dB within the band of interest. Meanwhile, the
      total efficiency and peak gain of each element, the envelope correlation
      coefficient (ECC) between the two elements are also improved by considerable
      amounts. All the results demonstrate that the proposed method is very efficient
      for enhancing the performance of MIMO antenna arrays.

PMID- 29453452
TI  - Systematic and stochastic influences on the performance of the MinION nanopore
      sequencer across a range of nucleotide bias.
AB  - Emerging sequencing technologies are allowing us to characterize environmental,
      clinical and laboratory samples with increasing speed and detail, including real
      time analysis and interpretation of data. One example of this is being able to
      rapidly and accurately detect a wide range of pathogenic organisms, both in the
      clinic and the field. Genomes can have radically different GC content however,
      such that accurate sequence analysis can be challenging depending upon the
      technology used. Here, we have characterized the performance of the Oxford MinION
      nanopore sequencer for detection and evaluation of organisms with a range of
      genomic nucleotide bias. We have diagnosed the quality of base-calling across
      individual reads and discovered that the position within the read affects base
      calling and quality scores. Finally, we have evaluated the performance of the
      current state-of-the-art neural network-based MinION basecaller, characterizing
      its behavior with respect to systemic errors as well as context- and sequence
      specific errors. Overall, we present a detailed characterization the capabilities
      of the MinION in terms of generating high-accuracy sequence data from genomes
      with a wide range of nucleotide content. This study provides a framework for
      designing the appropriate experiments that are the likely to lead to accurate and
      rapid field-forward diagnostics.

PMID- 29453454
TI  - A Microvascularized Tumor-mimetic Platform for Assessing Anti-cancer Drug
      Efficacy.
AB  - Assessment of anti-cancer drug efficacy in in vitro three-dimensional (3D)
      bioengineered cancer models provides important contextual and relevant
      information towards pre-clinical translation of potential drug candidates.
      However, currently established models fail to sufficiently recapitulate complex
      tumor heterogeneity. Here we present a chip-based tumor-mimetic platform
      incorporating a 3D in vitro breast cancer model with a tumor-mimetic
      microvascular network, replicating the pathophysiological architecture of native
      vascularized breast tumors. The microfluidic platform facilitated formation of
      mature, lumenized and flow-aligned endothelium under physiological flow
      recapitulating both high and low perfused tumor regions. Metastatic and non
      metastatic breast cancer cells were maintained in long-term 3D co-culture with
      stromal fibroblasts in a poly(ethylene glycol)-fibrinogen hydrogel matrix within
      adjoining tissue chambers. The interstitial space between the chambers and
      endothelium contained pores to mimic the "leaky" vasculature found in vivo and
      facilitate cancer cell-endothelial cell communication. Microvascular pattern
      dependent flow variations induced concentration gradients within the 3D tumor
      mass, leading to morphological tumor heterogeneity. Anti-cancer drugs displayed
      cell type- and flow pattern-dependent effects on cancer cell viability, viable
      tumor area and associated endothelial cytotoxicity. Overall, the developed
      microfluidic tumor-mimetic platform facilitates investigation of cancer-stromal
      endothelial interactions and highlights the role of a fluidic, tumor-mimetic
      vascular network on anti-cancer drug delivery and efficacy for improved
      translation towards pre-clinical studies.

PMID- 29453455
TI  - Temporal structure in spiking patterns of ganglion cells defines perceptual
      thresholds in rodents with subretinal prosthesis.
AB  - Subretinal prostheses are designed to restore sight in patients blinded by
      retinal degeneration using electrical stimulation of the inner retinal neurons.
      To relate retinal output to perception, we studied behavioral thresholds in blind
      rats with photovoltaic subretinal prostheses stimulated by full-field pulsed
      illumination at 20 Hz, and measured retinal ganglion cell (RGC) responses to
      similar stimuli ex-vivo. Behaviorally, rats exhibited startling response to
      changes in brightness, with an average contrast threshold of 12%, which could not
      be explained by changes in the average RGC spiking rate. However, RGCs exhibited
      millisecond-scale variations in spike timing, even when the average rate did not
      change significantly. At 12% temporal contrast, changes in firing patterns of
      prosthetic response were as significant as with 2.3% contrast steps in visible
      light stimulation of healthy retinas. This suggests that millisecond-scale
      changes in spiking patterns define perceptual thresholds of prosthetic vision.
      Response to the last pulse in the stimulation burst lasted longer than the steady
      state response during the burst. This may be interpreted as an excitatory OFF
      response to prosthetic stimulation, and can explain behavioral response to
      decrease in illumination. Contrast enhancement of images prior to delivery to
      subretinal prosthesis can partially compensate for reduced contrast sensitivity
      of prosthetic vision.

PMID- 29453457
TI  - Constructions of Unextendible Maximally Entangled Bases in [Formula: see text].
AB  - We study unextendible maximally entangled bases (UMEBs) in [Formula: see text] (d
      < d'). An operational method to construct UMEBs containing d(d' - 1) maximally
      entangled vectors is established, and two UMEBs in [Formula: see text] and
      [Formula: see text] are given as examples. Furthermore, a systematic way of
      constructing UMEBs containing d(d' - r) maximally entangled vectors in [Formula:
      see text] is presented for r = 1, 2, ..., d - 1. Correspondingly, two UMEBs in
      [Formula: see text] are obtained.

PMID- 29453456
TI  - Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration.
AB  - The goal of replenishing the cardiomyocyte (CM) population using regenerative
      therapies following myocardial infarction (MI) is hampered by the limited
      regeneration capacity of adult CMs, partially due to their withdrawal from the
      cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated in CMs
      during the postnatal switch from proliferation to terminal differentiation. In
      neonatal mice, cardiac-specific overexpression of miR-128 impairs CM
      proliferation and cardiac function, while miR-128 deletion extends proliferation
      of postnatal CMs by enhancing expression of the chromatin modifier SUZ12, which
      suppresses p27 (cyclin-dependent kinase inhibitor) expression and activates the
      positive cell cycle regulators Cyclin E and CDK2. Furthermore, deletion of miR
      128 promotes cell cycle re-entry of adult CMs, thereby reducing the levels of
      fibrosis, and attenuating cardiac dysfunction in response to MI. These results
      suggest that miR-128 serves as a critical regulator of endogenous CM
      proliferation, and might be a novel therapeutic target for heart repair.

PMID- 29453458
TI  - IL-2 Inducible Kinase ITK is Critical for HIV-1 Infection of Jurkat T-cells.
AB  - Successful replication of Human immunodeficiency virus (HIV)-1 depends on the
      expression of various cellular host factors, such as the interleukin-2 inducible
      T-cell kinase (ITK), a member of the protein family of TEC-tyrosine kinases. ITK
      is selectively expressed in T-cells and coordinates signaling pathways downstream
      of the T-cell receptor and chemokine receptors, including PLC-1 activation, Ca2+
      release, transcription factor mobilization, and actin rearrangements. The exact
      role of ITK during HIV-1 infection is still unknown. We analyzed the function of
      ITK during HIV-1 replication and showed that attachment, fusion of virions with
      the cell membrane and entry into Jurkat T-cells was inhibited when ITK was
      knocked down. In contrast, reverse transcription and provirus expression were not
      affected by ITK deficiency. Inhibited ITK expression did not affect the CXCR4
      receptor on the cell surface, whereas CD4 and LFA-1 integrin levels were slightly
      enhanced in ITK knockdown cells and heparan sulfate (HS) expression was
      completely abolished in ITK depleted T-cells. However, neither HS expression nor
      other attachment factors could explain the impaired HIV-1 binding to ITK
      deficient cells, which suggests that a more complex cellular process is
      influenced by ITK or that not yet discovered molecules contribute to restriction
      of HIV-1 binding and entry.

PMID- 29453459
TI  - Ultrahigh resolution radiation imaging system using an optical fiber structure
      scintillator plate.
AB  - High resolution imaging of radiation is required for such radioisotope
      distribution measurements as alpha particle detection in nuclear facilities or
      high energy physics experiments. For this purpose, we developed an ultrahigh
      resolution radiation imaging system using an optical fiber structure scintillator
      plate. We used a ~1-MUm diameter fiber structured GdAlO3:Ce (GAP) /alpha-Al2O3
      scintillator plate to reduce the light spread. The fiber structured scintillator
      plate was optically coupled to a tapered optical fiber plate to magnify the image
      and combined with a lens-based high sensitivity CCD camera. We observed the
      images of alpha particles with a spatial resolution of ~25 MUm. For the beta
      particles, the images had various shapes, and the trajectories of the electrons
      were clearly observed in the images. For the gamma photons, the images also had
      various shapes, and the trajectories of the secondary electrons were observed in
      some of the images. These results show that combining an optical fiber structure
      scintillator plate with a tapered optical fiber plate and a high sensitivity CCD
      camera achieved ultrahigh resolution and is a promising method to observe the
      images of the interactions of radiation in a scintillator.

PMID- 29453461
TI  - Roux-en-Y Gastric-Bypass and sleeve gastrectomy induces specific shifts of the
      gut microbiota without altering the metabolism of bile acids in the intestinal
      lumen.
AB  - Some shifts in the gut microbiota composition and its metabolic fingerprints have
      been associated to Sleeve gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB).
      So far, plasma bile acids have been associated with post-operative glucose
      improvement and weight loss, but nothing is known about their metabolism in the
      gut lumen. As bile acids are physiologically transformed by the microbiota into
      various species, the aim of this work was to study how SG and RYGB-associated
      dysbiosis impact the bioconversion of bile acids in the intestinal lumen.
      Comparing SHAM (n = 9) with our validated rat models of SG (n = 5) and RYGB (n =
      6), we quantified luminal bile acids along the gut and found that the metabolic
      transformation of bile acids (deconjugation, dehydroxylation, and epimerization)
      is not different from the duodenum to the colon. However, in the cecum where the
      biotransformation mainly takes place, we observed deep alterations of the
      microbiota composition, which were specific of each type of surgery. In
      conclusion, despite specific dysbiosis after surgery, the bile acids metabolism
      in the gut lumen is highly preserved, suggesting that a resilience of the gut
      microbiota occurs after these procedures.

PMID- 29453460
TI  - Development and initial characterization of a novel ghrelin receptor CRISPR/Cas9
      knockout wistar rat model.
AB  - BACKGROUND/OBJECTIVES: Ghrelin, a stomach-derived hormone implicated in numerous
      behaviors including feeding, reward, stress, and addictive behaviors, acts by
      binding to the growth hormone secretagogue receptor (GHSR). Here, we present the
      development, verification, and initial characterization of a novel GHSR knockout
      (KO) Wistar rat model created with CRISPR genome editing. METHODS: Using
      CRISPR/Cas9, we developed a GHSR KO in a Wistar background. Loss of GHSR mRNA
      expression was histologically verified using RNAscope in wild-type (WT; n = 2)
      and KO (n = 2) rats. We tested the effects of intraperitoneal acyl-ghrelin
      administration on food consumption and plasma growth hormone (GH) concentrations
      in WT (n = 8) and KO (n = 8) rats. We also analyzed locomotion, food consumption,
      and body fat composition in these animals. Body weight was monitored from early
      development to adulthood. RESULTS: The RNAscope analysis revealed an abundance of
      GHSR mRNA expression in the hypothalamus, midbrain, and hippocampus in WTs, and
      no observed probe binding in KOs. Ghrelin administration increased plasma GH
      levels (p = 0.0067) and food consumption (p = 0.0448) in WT rats but not KOs. KO
      rats consumed less food overall at basal conditions and weighed significantly
      less compared with WTs throughout development (p = 0.0001). Compared with WTs,
      KOs presented higher concentrations of brown adipose tissue (BAT; p = 0.0322).
      CONCLUSIONS: We have verified GHSR deletion in our KO model using histological,
      physiological, neuroendocrinological, and behavioral measures. Our findings
      indicate that GHSR deletion in rats is not only associated with a lack of
      response to ghrelin, but also associated with decreases in daily food consumption
      and body growth, and increases in BAT. This GHSR KO Wistar rat model provides a
      novel tool for studying the role of the ghrelin system in obesity and in a wide
      range of medical and neuropsychiatric disorders.

PMID- 29453462
TI  - GQ-11: A new PPAR agonist improves obesity-induced metabolic alterations in LDLr
      /- mice.
AB  - BACKGROUND: Obesity and insulin resistance/diabetes are important risk factors
      for cardiovascular diseases and demand safe and efficacious therapeutics.
      OBJECTIVE: To assess the effects of a new thiazolidine compound-GQ-11-on obesity
      and insulin resistance induced by a diabetogenic diet in LDL receptor-deficient
      (LDLr-/-) mice. METHODS: Molecular docking simulations of GQ-11, PPARalpha and
      PPARgamma structures were performed. Male C57BL/6J LDLr-/- mice fed a
      diabetogenic diet for 24 weeks were treated with vehicle, GQ-11 or pioglitazone
      or (20 mg/kg/day) for 28 days by oral gavage. Glucose tolerance test, insulin,
      HOMA-IR, adipokines (leptin, adiponectin) and the lipid profile were assessed
      after treatment. Adipose tissue was analysed by X-ray analysis and morphometry;
      gene and protein expression were evaluated by real-time PCR and western blot,
      respectively. RESULTS: GQ-11 showed partial agonism to PPARgamma and PPARalpha.
      In vivo, treatment with GQ-11 ameliorated insulin sensitivity and did not modify
      subcutaneous adipose tissue and body weight gain. In addition, GQ-11 restored
      adipokine imbalance induced by a diabetogenic diet and enhanced Glut-4 expression
      in the adipose tissue. Improved insulin sensitivity was also associated with
      lower levels of MCP-1 and higher levels of IL-10. Furthermore, GQ-11 reduced
      triglycerides and VLDL cholesterol and increased HDL-cholesterol by upregulation
      of Apoa1 and Abca1 gene expression in the liver. CONCLUSION: GQ-11 is a
      partial/dual PPARalpha/gamma agonist that demonstrates anti-diabetic effects.
      Additionally, it improves the lipid profile and ameliorates chronic inflammation
      associated with obesity in atherosclerosis-prone mice.

PMID- 29453463
TI  - Impact of gastric emptying and small intestinal transit on blood glucose,
      intestinal hormones, glucose absorption in the morbidly obese.
AB  - OBJECTIVE: This study evaluated gastric emptying (GE) and small intestinal (SI)
      transit in people with morbid obesity and their relationships to glycaemia,
      incretin hormones, and glucose absorption METHODS: GE and caecal arrival time
      (CAT) of a mixed meal were assessed in 22 morbidly obese (50.2 +/- 2.5 years; 13
      F:9 M; BMI: 48.6 +/- 1.8 kg/m2) and 10 lean (38.6 +/- 8.4 years; 5 F:5 M; BMI:
      23.9 +/- 0.7 kg/m2) subjects, using scintigraphy. Blood glucose, plasma 3-O
      methylglucose, insulin, glucagon, glucose-dependent insulinotropic polypeptide
      (GIP) and glucagon-like peptide-1 (GLP-1) were measured. Insulin sensitivity and
      resistance were also quantified RESULTS: When compared with lean subjects, GE
      (t50: 60.7 +/- 6.5 vs. 41.1 +/- 7.3 min; P  = 0.04) and CAT (221.5 +/- 9.8 vs.
      148.0 +/- 7.1 min; P =  0.001) of solids were prolonged in morbid obesity.
      Postprandial rises in GIP (P = 0.001), insulin (P  = 0.02), glucose (P = 0.03)
      and 3-O-methylglucose (P = 0.001) were less. Whereas GLP-1 increased at 45 mins
      post-prandially in lean subjects, there was no increase in the obese (P  = 0.04).
      Both fasting (P = 0.045) and postprandial (P = 0.012) plasma glucagon
      concentrations were higher in the obese CONCLUSIONS: GE and SI transit are slower
      in the morbidly obese, and associated with reductions in postprandial glucose
      absorption, and glycaemic excursions, as well as plasma GIP and GLP-1.

PMID- 29453464
TI  - Dietitian-led lifestyle modification programme for obese Chinese adolescents with
      non-alcoholic fatty liver disease: a randomized controlled study.
AB  - BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) in
      children is increasing. This study evaluated the efficacy of a dietitian-led
      lifestyle modification programme (D-LMP) to reduce NAFLD in obese adolescents.
      METHODS: Subjects with intra-hepatic triglyceride content (IHTC) equal to or
      greater than 5% diagnosed by proton-magnetic resonance spectroscopy (1H-MRS) were
      enroled and randomly assigned to either the D-LMP intervention or conventional
      paediatrician-led consultation (P-CON) group. Subjects in the P-CON group
      received usual care consisting of a consultation by a paediatrician with the
      child and parents every 16 weeks. Intention-to-treat analysis was used for data
      analysis. RESULTS: Fifty-two subjects were recruited, with 26 in each group.
      After the initiation phase (at week-16), there was a greater difference in the
      change in the IHTC and BMI z-score in the D-LMP group (P = 0.029 and <0.001,
      respectively) and there was a decrease in dietary intake of fat content (P =
      0.019). After 52 weeks of the maintenance phase, both groups had reductions of
      IHTC to 2-3% and there was no intergroup difference in the rate of reduction.
      During the maintenance phase, parents' involvement was minimal in the D-LMP
      group, with only three parents accompanying their children to attend the
      dietitian sessions. In contrast, over 90% of the parents in the P-CON group
      regularly accompanied their children to attend the consultations suggesting the
      possibility that regular parental and paediatrician involvement may contribute to
      increasing awareness on fatty liver complications. Multivariate analysis showed
      that only reduction in body fat remained as an independent factor associated with
      remission of NAFLD at the end of both study phases. CONCLUSIONS: A dietitian-led
      lifestyle modification intervention reduced IHTC, BMI z-score and body fat in
      obese Chinese adolescents with NAFLD. To sustain the effect of this intervention,
      regular parental and paediatrician involvement may be important.

PMID- 29453465
TI  - Screening of potential adipokines identifies S100A4 as a marker of pernicious
      adipose tissue and insulin resistance.
AB  - BACKGROUND: Adipokines are peptides secreted from white adipose tissue (WAT),
      which have been linked to WAT dysfunction and metabolic complications of obesity.
      We set out to identify novel adipokines in subcutaneous WAT (sWAT) linked to
      insulin resistance (IR). METHODS: Gene expression was determined by microarray
      and qPCR in obese and non-obese subjects with varying degree of IR. WAT-secreted
      and circulating protein levels were measured by ELISA. RESULTS: In sWAT of 80
      obese women discordant for IR, 44 genes encoding potential adipose-secreted
      proteins were differentially expressed. Among these, merely two proteins, S100A4
      and MXRA5 were released from sWAT in a time-dependent manner (criterion for true
      adipokines) but only the circulating levels of S100A4 were higher in IR. In two
      additional cohorts (n = 29 and n = 56), sWAT S100A4 secretion was positively and
      BMI-independently associated with IR (determined by clamp or HOMA-IR), ATP-III
      risk score and adipocyte size (hypertrophy). In non-obese (n = 20) and obese
      subjects before and after bariatric surgery (n = 21), circulating and sWAT
      secreted levels were highest in the obese and normalized following weight loss.
      Serum S100A4 concentrations were higher in subjects with type 2 diabetes. S100A4
      sWAT expression associated positively with genes involved in
      inflammation/extracellular matrix formation and inversely with genes in metabolic
      pathways. Although S100A4 was expressed in both stromal cells and adipocytes,
      only the expression in adipocytes associated with BMI. CONCLUSIONS: S100A4 is a
      novel adipokine associated with IR and sWAT inflammation/adipocyte hypertrophy
      independently of BMI. Its value as a circulating marker for dysfunctional WAT and
      IR needs to be validated in larger cohorts.

PMID- 29453466
TI  - Effects of Intrathecal Dexmedetomidine as an Adjuvant to Hyperbaric Bupivacaine
      for Spinal Anaesthesia in Adults Undergoing Elective Infra-umbilical Surgery.
AB  - INTRODUCTION: Various adjuvants to local anaesthetic are used to improve quality
      and duration of spinal anaesthesia. Dexmedetomidine, a novel alpha-2 adrenergic
      agonist, has been proposed to augment local anaesthetic effects. This study aims
      to investigate effects of intrathecal Dexmedetomidine on duration of analgesia
      and duration of sensory block during spinal anaesthesia. METHODS: In this
      randomized double-blind study 38 patients were allocated into each of two groups.
      Otherwise healthy patients (18 to 75 years) scheduled for inguinal hernia repair
      or vaginal hysterectomy were included. For spinal anaesthesia, Group A received
      2.5 ml hyperbaric Bupivacaine 0.5%, whereas Group B received five micrograms
      intrathecal Dexmedetomidine in addition. Characteristics of sensory and motor
      blocks, duration of analgesia, analgesic requirements, and side effects were
      studied for 24 hours. Student's t-test for quantitative variables and Chi-
      squared test for qualitative variables were used for statistical analysis.
      RESULTS: Duration of analgesia was prolonged in Group B (326 min +/-91) as
      compared to 217 min +/-98 in Group A (P value <0.05). Sensory and motor block
      durations were significantly prolonged in Group B. Time taken to reach
      significant peak sensory block level was earlier in Group B. Significant
      reductions in incidence of visceral pain, shivering and analgesic requirements
      were observed in Dexmedetomidine group, without increased need of medications for
      altered hemodynamic parameters. CONCLUSIONS: Dexmedetomidine as an intrathecal
      adjuvant to hyperbaric Bupivacaine in spinal anaesthesia prolongs duration of
      analgesia and sensory block with minimal adverse effects.

PMID- 29453467
TI  - Loading Dose only versus Standard Dose Magnesium Sulfate Seizure Prophylaxis in
      Severe Pre-eclamptic Women.
AB  - INTRODUCTION: Magnesium sulfate is the drug of choice for prevention of seizures
      in the pre-eclamptic woman. There is no agreement in the published randomized
      trials regarding the optimal time to initiate magnesium sulfate, the dose to use
      (both loading and maintenance) as well as the duration of therapy. The objective
      of this study is to determine whether magnesium sulfate prophylaxis is needed for
      up to 24 hours postpartum in all patients with severe pre-eclampsia for the
      prevention of seizure. METHODS: It is a randomized controlled trial conducted on
      60 pregnant women with severe preeclampsia randomized into standard dose and
      loading dose only regimen. RESULTS: Out of 30 cases in each group 1 (3.3%)
      patient in standard regimen and 2 (6.7%) patients in loading dose only developed
      seizure. The occurrence of seizure is not significant statistically. In both
      regimens, there was no maternal mortality. Total of 3 patients needed MICU care
      and 12 patient developed maternal complications. MgSO4 toxicities were seen only
      in standard dose regimen that is in 17 (56.7%) of the patients. The median number
      of IM injections of MgSO4 received in standard dose regimen was 8+/-2.176. In
      standard dose regimen 73.3 percent baby were alive whereas in case of loading
      dose only regimen 93.3 percent of baby were alive after 48 hours of delivery.
      CONCLUSIONS: Single dose of magnesium sulfate is equally effective as standard
      dose regimen in terms of seizure prophylaxis in severe pre eclamptic women, with
      added advantage of reduced maternal toxicity and better neonatal outcome.

PMID- 29453468
TI  - Prevention of Shivering during Spinal Anesthesia: Comparison between Tramadol,
      Ketamine and Ondansetron.
AB  - INTRODUCTION: Shivering is an unpleasant experience after spinal anesthesia. We
      conducted this study to evaluate the efficacy of ondansetron, ketamine and
      tramadol for prevention of shivering. METHODS: In this randomized controlled
      study, 120 patients aged 18-65 years of American Society of Anesthesiologist
      (ASA) physical status I and II undergoing various surgical procedures were
      included and allocated alternately to one of the 4 groups; Normal saline
      (Group1), Ondansetron 4mg (Group2), Ketamine 0.25mg/kg (Group3) and Tramadol
      0.5mg/kg (Group4). Incidence of shivering, effect on hemodynamics, nausea,
      vomiting, sedation and emergence reactions were recorded. Data was analyzed using
      SPSS (The Statistical Package for Social Sciences) version 20.0 software.
      RESULTS: The patients were comparable in terms of demographic variables, baseline
      temperature, type of surgery, median level of sensory blockade, duration of
      surgery and anesthesia. Shivering was present in 17 (56.7%), 5 (16.7%), 3 (10%)
      and 3 (10%) patients respectively in Group 1, 2, 3 and 4 which was statistically
      significant when compared to Group 1 (P=0.00) The odds of NS and ondansetron, NS
      and ketamine, NS and tramadol was 6.53, 11.76 and 11.76 respectively which showed
      that study drugs were effective in preventing shivering. None of the patients
      were sedated in Group 1 and 2. Mild to moderate sedation was present in Group 3
      and 4 (P=0.00). None of the patients had drug related adverse reactions.
      CONCLUSIONS: Prophylactic use of ondansetron, low doses of ketamine and tramadol
      is effective in preventing shivering post spinal anesthesia without untoward
      effects.

PMID- 29453469
TI  - Demographic and Clinical Profile in Patients with Liver Cirrhosis in a Tertiary
      Care Hospital in Central Nepal.
AB  - INTRODUCTION: Liver cirrhosis is an important health problem worldwide and is a
      common disease in Nepal. The profile of cirrhosis may vary due to different
      factors. This study was undertaken to see the demographic and clinical profiles
      of patients with cirrhosis of liver attending a tertiary care hospital in Central
      Nepal. METHODS: Six hundred patients with clinical features, laboratory and
      sonological findings suggestive of chronic liver dysfunction and endoscopic
      evidence of portal hypertension were included in the study. Their demographic and
      clinical profile, endoscopic findings, outcomes during hospitalization were
      studied. Ethical approval was taken from Institutional Review Committee of
      College of Medical Sciences. SPSS 20 was used for statistical analysis. RESULTS:
      The mean age of subjects was 54+/-11.84 years with 435 males (72.5%) and 165
      (27.5%) females. Majority of 203 (33.8%) patients were from Mongol ethnicity
      followed by 127 (21.2%) Khas. Two hundred and twenty (36.6%) were farmers
      followed by 169 (28.2%) retired personnel. A total of 338 (56.4 %) patients were
      from rural areas. The commonest aetiology of cirrhosis was chronic alcohol
      consumption and seen in 552 (92%) patients. Abdominal distension was commonest
      presenting sign and observed in 561 (93.5%) patients. Ascites seen in 555 (92.5%)
      patients was the commonest complication followed by UGI bleed in 326 (54.3%)
      patients. Gastro-oesophageal varices observed in 345 (57.5%) patients, was the
      most common endoscopic finding followed by portal gastropathy, peptic ulcer and
      erosive mucosal diseases. In patient mortality was noted in 92 (15.3 %) patients.
      CONCLUSIONS: This study highlights the burden of cirrhosis, usually caused by
      chronic alcohol consumption in Central Nepal. Majority of subjects were male,
      middle aged, farmers, from rural areas and predominantly observed in some
      ethnicity like Mongols. Cirrhotic patients usually Keywords: cirrhosis of liver;
      complications; endoscopy.

PMID- 29453470
TI  - Nerve Conduction and Heart Rate variability in Patients with Hypothyroidism at a
      Tertiary Care Centre in Eastern Nepal.
AB  - INTRODUCTION: Thyroid hormone effects on many organs including central and
      peripheral nervous systems. However, these hormones do not affect all
      systems/organs to a similar extent. Thus, we conducted this study to explore the
      effect of thyroid hormones on somatic nervous system assessed by Nerve conduction
      study and cardiac autonomic activity assessed by heart rate variability. METHODS:
      The study included newly diagnosed hypothyroid patients and healthy controls. In
      all subjects NCS were performed in median, ulnar, tibial and sural nerves using
      Nihonkohden machine Cardiac autonomic control was assessed using Short-term Heart
      Rate Variability and parameters were analyzed by Time Domain and Frequency Domain
      methods. RESULTS: Both the groups were comparable in term of age, Body Mass
      Index, Pulse Rate, Systolic Blood Pressure and Diastolic Blood Pressure. Sensory
      parameters of NCS showed significant decrease in left median nerve SNAP amplitude
      (38.24+/-10.23 Vs 31.59+/-14.06, P=0.048) and nerve conduction velocity of
      bilateral median nerve in hypothyroid patients. In motor parameters of NCS, onset
      latencies of bilateral median nerves and right ulnar nerve were significantly
      increased in hypothyroid patients. All Time Domain measures of HRV and Frequency
      Domain measures; LF Power, HF Power and Total Power were significantly decreased
      (P<0.05) in hypothyroid patients. These HRV parameters are indicators of
      parasympathetic activity. CONCLUSIONS: In newly diagnosed hypothyroid patients,
      especially median nerve functions (both sensory and motor) and parasympathetic
      activity were decreased. It reflects that in hypothyroidism both autonomic
      nervous system and other somatic nerves are not affected in a similar extent.

PMID- 29453471
TI  - Significance of Non-Invasive Markers as Predictor of Esophageal Varices in Liver
      Cirrhosis.
AB  - INTRODUCTION: Upper gastro-intestinal endoscopy remains the gold standard for
      screening for esophageal varices but it has its own limitations. It is an
      invasive, expensive and uncomfortable procedure and needs clinical expertise.
      Accordingly, this study was conducted to establish the role of non-invasive
      markers for prediction of esophageal varices in liver cirrhosis. METHODS: A
      hospital based descriptive cross-sectional study was carried out in Liver unit of
      National Academy of Medical Sciences, Bir Hospital, from October 2016 to
      September 2017. Complete blood count, liver function test, liver ultrasound and
      upper gastro-intestinal endoscopy were done for all patients to detect esophageal
      varices and to correlate with different non-invasive markers. RESULTS: Total 191
      patients of liver cirrhosis were studied after exclusion. Platelet count of
      92082.00+/-43435.83/mm3 and spleen size of 144.21+/-10.71 mm was found to be good
      predictors of presence of EV (P<=0.001). Significant association between Child
      Turcotte-Pugh class and presence of varices was observed (P<=0.001). AST/ALT
      ratio with cutoff value of 1.415 showed sensitivity of 82.4% and specificity of
      36.4%. APRI at a cutoff value of 1.3 showed a sensitivity of 83.2% and
      specificity of 50%. CONCLUSIONS: Platelet count, spleen size and Child-Turcotte
      Pugh class are good predictors of presence of esophageal varices in patients with
      liver cirrhosis. AST/ALT ratio and APRI score are not good substitutes for upper
      gastro-intestinal endoscopy.

PMID- 29453472
TI  - Prevalence of Hepatitis D Among Patients with Hepatitis B Viral Infection
      Attending a Tertiary Care Centre of Nepal.
AB  - INTRODUCTION: Worldwide there is variation in prevalence of Hepatitis D viral
      infection. Superinfection and co infection with hepatitis B viral infection is
      known to occur in 15-20 million people. METHODS: This was a descriptive cross
      sectional hospital based study carried out in NAMS, Bir hospital, Kathmandu,
      Nepal from period of January 2017 to June 2017. Consecutive patients of chronic
      hepatitis B viral infection of HBsAg positive with more than two-time upper
      normal limit of ALT were enrolled and tested for HDV IgG. RESULTS: Forty patients
      were enrolled during study period. Mean age was 30.9+/-12.2 years. Males were 28
      (70%) and females 12 (30%). Most of the patients were asymptomatic for HBV
      infection 32 (80%). HBeAg negative chronic hepatitis was most commonly present in
      31 (77.5%). Family history of Hepatitis B viral infection was seen in 7 (17.5%)
      and sexual promiscuity in 5 (12.5%) as the mode of acquisition of hepatitis B
      viral infection. HBcIgM was positive in three patients with mean HBV DNA of
      4.97x105+/-4.5x105 IU/ml in HBeAg positive group. HDV IgG was negative in all
      patients. CONCLUSIONS: Coinfection and superinfection of hepatitis D virus were
      found to be uncommon at Bir hospital, Nepal.

PMID- 29453473
TI  - Prehospital Events in ST- Elevation Myocardial Infarction Undergoing Primary
      Angioplasty.
AB  - INTRODUCTION: Pre-hospital delay includes time from onset of symptoms of
      myocardial infarction till arrival to emergency room of the hospital. This
      defines time from symptom onset to first medical contact and first medical
      contact to emergency room. This study aims to study the prehospital events and
      determining factors in patients undergoing primary angioplasty. METHODS: This was
      a cross sectional study in Shahid Gangalal National Heart Centre for three
      months. Timings of chest pain, first medical contact time, transfer time to
      hospital and overall pre-hospital time for PCI and risk factors were analysed.
      RESULTS: There were 79 cases with 66 (83.5%) males and 13 (16.5%) females with
      mean age 56+/-11.2 years. Risk factors were 60 (75.9%), smoking, 47 (59.5%)
      hypertension, 25 (31.6%) diabetes, 22 (27.8%) dyslipidaemia and 16 (20.3%) heart
      failure. Chest pain was maximum in 5 to 9 AM. The median prehospital delay was
      300 minutes (5.0 hours) of which symptom to first medical contact was 165 minutes
      and first medical contact to hospital was 80 minutes. The longer median
      prehospital delay for hypertension, diabetes, female and age >=50 years and the
      shorter for male, age less than 50 years, dyslipidemia and heart failure, though
      not statistically significant. Private transport was the preferred from symptom
      to first medical contact and ambulance for first medical contact to emergency
      room. Patients received in ER had aspirin 72 (91.1%), atorvastatin 54 (68.4%) and
      double anti-platelets 45 (57%). CONCLUSIONS: Chest pain was common in morning and
      the prehospital delay can be minimized by improving time from symptom to first
      medical contact and first medical contact to Emergency room.

PMID- 29453474
TI  - Fingerprints as an Alternative Method to Determine ABO and Rh Blood Groups.
AB  - INTRODUCTION: Blood grouping is conventionally done with invasive method by
      taking blood samples. The objective of this study is to determine blood group
      with uninvasive procedure by taking fingerprints of the participants and know the
      associations between their fingerprints and blood groups. METHODS: Seven hundred
      participants of both genders with no any age limitation from Manipal Teaching
      Hospital and Manipal College of Medical Sciences were randomly selected. The
      blood grouping was done by cross reacting blood sample with the antibodies. The
      fingerprints were taken with the help of stamp pad imprinting the finger ridges
      over A4 size white papers. The loop, whorl and arch patterns were studied.
      RESULTS: O+ve blood group 224 (32%) was most prevalent among 700 participants.
      The loop pattern was highly distributed 3708 (53%) in all blood groups except in
      A-ve blood group with highest distribution of whorl 20 (40%). The mean
      comparisons of specific fingerprint in total and also in individual fingers with
      different ABO and ABO-Rh blood groups showed no any statistical association with
      P>0.05. However, the loop distribution in individual finger was highest in right
      middle finger (M) of B-ve blood group 5 (10%). The whorl distribution in
      individual finger was highest in right index (I), left thumb (T) and left ring
      (R) fingers of AB+ve blood group 20 (5.5% each). Similarly, the arch distribution
      was highest in right index fingers of A-ve blood group 3 (6%). CONCLUSIONS: The
      mean comparison of different fingerprints with ABO and Rh blood groups showed no
      significant statistical association concluding fingerprints cannot be used for
      blood grouping.

PMID- 29453475
TI  - Basal Cell Carcinoma in Cases with or without Xeroderma Pigmentosum.
AB  - INTRODUCTION: Basal cell carcinoma is the most common form of cancer in humans
      and comprises the vast majority of skin cancers. It predominantly affects fair
      skinned individuals, and its incidence is rapidly increasing. The objective of
      the study is to identify the epidemiology, its topography and different
      histological subtypes of basal cell carcinoma in patients with or without
      Xeroderma Pigmentosum. METHODS: A cross-sectional descriptive study was conducted
      at Manipal Teaching Hospital, Pokhara from Jan 2009 to Dec 2016. Ethical approval
      was taken from MEMG/IRC/GA. The study included patients with a confirmed
      diagnosis of basal cell carcinoma irrespective of their age and sex. RESULTS:
      This study showed 77 individuals with 91 biopsies of BCC including 5 cases of
      Xeroderma Pigmentosum. The predominant histological subtype was nodular with 41
      (53.94%) cases, followed by the 14 (18.42%) cases of pigmented and 10 (13.15%)
      cases baso-squamous subtype. The most frequent sites of involvement were the head
      and neck, with predominance in the nasal and orbital region. The mean age was
      57.68 years but the basal cell carcinoma in cases of Xeroderma Pigmentosum was
      seen more in younger age groups. There were 43 (55.84 %) male patients and 34
      (44.16 %) female patients with a male to female ratio of 1.26:1. CONCLUSIONS:
      Nodular and pigmented varieties were the most frequent subtypes with nose being
      the commonest site of involvement. Basal cell carcinomas in cases of Xeroderma
      Pigmentosum were noted in younger age group with multiple lesions.

PMID- 29453476
TI  - Postoperative Outcome in Patients with Pulmonary Hypertension Undergoing Elective
      Non-Cardiac Surgery.
AB  - INTRODUCTION: The impact of pulmonary artery hypertension on post-operative
      outcome in elective, non-cardiac surgery is incompletely understood. This study
      was designed to evaluate the post-operative outcome of patients undergoing
      elective, non-cardiac surgery with and without pulmonary hypertension. METHODS:
      The study was conducted in an inner-city hospital in Bronx, New York. A
      retrospective chart review was conducted on all patients who underwent elective,
      non- cardiac surgery from January 2000 to December 2010 and had echocardiogram
      within 30 days of surgery. Patients with systolic pressure of >=35mm of Hg as
      estimated by echocardiogram were enrolled. Case matched peers with normal
      pulmonary pressures served as controls. Post-operative outcomes were compared
      between the two groups. RESULTS: A total of 66 patients were analysed, 33 cases
      and 33 controls. All patients were followed up to 30-day post-surgery. Heart
      failure, myocardial infarction, arrhythmia, stroke, delayed extubation and deaths
      were measured in both the groups. There were two deaths in the control group
      while there were three deaths in pulmonary hypertension group (statistically not
      significant, P >0.05). A total of three patients in pulmonary hypertension group
      had adverse outcome (one had a major arrhythmia, one had delayed extubation (>24
      hours) and one had stroke). Whereas two patients in control group had adverse
      outcome (one had delayed extubation (>24 hours) and one had major arrhythmia).
      CONCLUSIONS: Pulmonary hypertension does not affect the post-operative outcome in
      the first 30 days for elective non-cardiac surgery.

PMID- 29453477
TI  - Effects of Bilateral Nasal Packing on Oxygen Saturation and Blood Pressure.
AB  - INTRODUCTION: Nasal packing is one of the most common rhinological procedures in
      ENT practice exerting local in nose and systemic effects. Systemic effects may be
      due to poor sleep quality, respiratory difficulty, decreased oxygen saturation,
      circulatory problems and toxic shock syndrome which can threaten the life of a
      person.The study was done to investigate the effect on bilateral nasal packing on
      blood oxygen saturation and blood pressure changes. METHODS: A cross-sectional
      prospective study was undertaken in Kathmandu Medical College from January 2017
      to June 2017. The ethical approval was taken from institutional review committee
      of KMC and verbal consent was taken from each patient. Thirty patients were
      included in the study by simple randomized sampling. The association between
      nasal packing and oxygen saturation and blood pressure was done using ANNOVA and
      Fisher Exact test. P value of <0.005 was considered statistically significant.
      SPSS version 20 for windows OS was used for analysis. RESULTS: Blood oxygen
      saturation on four different days was compared using ANNOVA and paired sample
      tests. It showed a significant dip on the day of bilateral nasal packing compared
      to other readings (P value <0.001). Likewise, systolic and diastolic blood
      pressures showed a significant rise on the day of bilateral nasal packing
      compared to readings on other days (P value <0.001). CONCLUSIONS: Bilateral nasal
      packing can lead to significant rise in systolic and diastolic blood pressure and
      a dip in blood oxygen saturation. Thus care has to be taken while performing
      bilateral nasal packing in normal patients but much more in high risk patients.

PMID- 29453478
TI  - Endoscopic Sinus Surgery for Sinonasal Polyposis: Microdebrider or Conventional
      Instruments.
AB  - INTRODUCTION: Sinonasal polyposis is one of the commonest causes of nasal
      obstruction. Surgical management is treatment of choice. Microdebrider offers
      more advantage to conventional instruments. We aimed to find out outcome using
      microdebrider versus conventional instruments in endoscopic sinus surgery of
      sinonasal polyposis. METHODS: The cross sectional descriptive study carried out
      in patients aged 13 years and above with diagnosis of sinonasal polyposis. Total
      of 51 patients were operated on the right side with microdebrider and left side
      with conventional instruments. Postoperatively each patient assessed for nasal
      obstruction subjectively and by endoscopic examination to look for mucosal
      oedema, synechiae and recurrence at 4 weeks and 8 weeks postoperatively. RESULTS:
      The incidence of mucosal oedema in microdebrider and conventional instruments at
      4 weeks and 8 weeks was statistically not significant with P value 0.089, 0.322
      respectively. The incidence of synechiae in conventional group was more than
      microdebrider 1 (2%) versus 4 (7.8%) at 4 weeks follow up but the difference was
      statistically not significant (P value 0.773). There were 2 (3.9%) recurrences in
      microdebrider group and 3 (5.8%) recurrences in conventional group with P value
      0.532. CONCLUSIONS: Use of microdebrider offered fewer incidences of synechiae
      and recurrence. But we couldn't find statistical advantage over conventional
      instruments.

PMID- 29453479
TI  - Blood Pressure and its Association with Body Mass Index Among the People
      Attending in a Hospital.
AB  - INTRODUCTION: Systolic and diastolic hypertension has been increasing trend and
      different factors are associated such as body mass index, diabetes etc. Obesity
      and overweight are generally associated with high blood pressure. This study aims
      to identify the prevalence of blood pressure level and its association to body
      mass index among people attending in civil service hospital, Kathmandu. METHODS:
      A cross-sectional descriptive study was conducted among all 1002 study subjects
      aged above 20 years. Information were obtained from people coming for Master
      health check-up during study period. Blood pressure and weight were taken by WHO
      certified tool. RESULTS: Half of the respondents were overweight and obese.
      Prevalence of systolic and diastolic hypertension was found to be 171 (17.1%) and
      310 (30.9%) respectively. There is significant difference between body mass index
      to sex. Females are 1.5 times more likely to have high blood pressure who have
      high body mass index. Age group (40-59) years are more than two times likely to
      have overweight, systolic and diastolic blood pressure than other age group.
      Systolic blood pressure is more than six times more likely to be high in 60+ age
      group. But it is only 2.6 times in diastolic blood pressure and in body mass
      index, it is reduced to 1.4 times but it was still statistically significant.
      Overweight people are 1.4 and 1.6 times more likely to have high systolic and
      diastolic BP than another category. CONCLUSIONS: Half of the respondents were
      overweight and obese. Male had high overweight and obesity than female.
      Overweight people more likely to have high systolic and diastolic BP than others.

PMID- 29453480
TI  - Limited Open Reduction and Percutaneous Plate Osteosynthesis - Alternative Option
      to Minimally Invasive Plate Osteosynthesis in Management of Distal Tibia
      Fractures.
AB  - INTRODUCTION: The management of distal tibia fracture is challenging because of
      the limited soft tissue coverage and poor vascularity around the bone in that
      area. Minimally invasive percutaneous plate osteosynthesis is a novel technique
      in this regard but needs fluoroscopy. In unavailability of fluoroscopy or its
      technical malfunction, limited open reduction percutaneous plate osteosynthesis
      becomes useful. The aim of this study is to compare the outcomes of distal tibia
      fractures treated by LORPPO and MIPPO techniques in terms of duration of hospital
      stay, full weight bearing, union time and complications. METHODS: Twenty-two
      cases of closed distal tibia fractures without articular involvement or
      comminution operated at Koshi Zonal Hospital, Nepal from March 2014 to May 2016
      were included in this study. Total 11cases of which were treated by MIPPO whereas
      other 11 cases were treated by LORPPO. MIPPO technique was done only when the
      fluoroscopy was available. RESULTS: In MIPPO, the average age of the patients
      were 43.72 (range 23-65) years, hospital stay mean duration 8.45 (range 6-12)
      days, full weight-bearing walking was started in 11.27 (range 9-15) weeks and
      average radiological union time was 21.25 (range 18-28) weeks. In LORPPO, the
      mean age was 46.36 (range 25-70)years, hospital stay mean 11.81 (range 10-15)
      days, full weight bearing walking mean 10.63 (range 9-15) weeks and average
      radiological union time was 23.0 (range 19-27) weeks. CONCLUSIONS: The outcomes
      are comparatively similar for both the techniques. LORPPO could be an alternative
      to MIPPO in the management of distal tibia fractures.

PMID- 29453481
TI  - Ventilator-Associated Pneumonia and Role of Nurses in Its Prevention.
AB  - Ventilator-associated pneumonia (VAP) is one of the most frequent nosocomial
      infections among ventilated patients in ICUs, associated with an increase in days
      of ICU stay, morbidity, and mortality. Its prevention is a significant concern in
      every hospital. Most of the interventions and prevention strategies are part of
      routine nursing care. Nurses have different vital roles such as care provider,
      manager, educator, coordinator, and evaluator in preventing VAP. Lack of
      knowledge of infection prevention and proper nursing care among nurses may become
      a barrier in adhering to evidence-based guidelines for preventing ventilator
      associated pneumonia. This study will help nurses to know about VAP and its
      prevention in detail so that they can apply the knowledge in clinical practice.
      Understanding pathophysiology of VAP, its risk factors, and care bundle is vital
      for the proper prevention and treatment of VAP. There must be specific protocols,
      strategies and active surveillance in every ICU regarding the care bundle.

PMID- 29453482
TI  - Identification of Deceased Children of Nepal Airlines Crash through Dental Age
      Estimation.
AB  - Identification of victims in a disaster is a challenging process and requires use
      of both primary and secondary identifiers. Development of teeth is one of the
      routinely used methods of age estimation and helps in establishing deceased
      biological profile. Two children who lost their lives in 2014 in Nepal Airlines
      crash, were looked for the dental developmental status. One of the children had
      primary dentition, while the other had mixed dentition. This helped us in
      estimating age of these individuals reconciled with the chronological age
      provided by the relatives. This led to the identification of both the children,
      thus, emphasizing teeth as important means of identification in any disaster.

PMID- 29453483
TI  - Chorioangioma of Placenta.
AB  - Chorioangioma of placenta is the commonest benign tumour of the placenta. It
      consists of a benign angioma arising from chorionic tissue. We report a case of
      placental chorioangioma which was diagnosed in the post partum period in a
      patient with polyhydramnios who went into preterm labor and delivered a premature
      baby.

PMID- 29453484
TI  - Late Presentation of Post Diphtheritic Myocarditis in a 15-year Male.
AB  - A 15-year old male patient presented to us with dyspnoea for four days. He had a
      history of fever, pseudo-membranous tonsillitis and cervical adenopathy twenty
      five days prior to the presentation. On examination and laboratory
      investigations, he had features suggestive of myocarditis with biventricular
      failure. There was no reliable history of immunisation and he had a positive
      history of contact. He was planned for anti-diphtheria toxin but before the anti
      toxin could be initiated, the patient succumbed to refractory cardiogenic shock.
      This was a rare case of late onset diphtheritic myocarditis in an unimmunised
      adult. With the advent of universal immunisation, there has been a significant
      decline in the incidence but there is still some road to cover.

PMID- 29453485
TI  - Oral Squamous Papilloma of Edentulous Mouth Interfering with Denture Retention.
AB  - Soft tissue overgrowths inside oral cavity can present with wide range of
      clinical manifestations and some of them can asymptomatic. Oral squamous
      papilloma is one of that asymptomatic lesion described in the literature with
      extremely low virulence and infectivity rate. Soft tissue overgrowths can
      sometimes interfere with denture retention. Here we report a case of squamous
      papilloma in a 60 years old edentulous female who presented with loss of denture
      retention.

PMID- 29453486
TI  - Immune System and Kidney Transplantation.
AB  - The immune system recognises a transplanted kidney as foreign body and mounts
      immune response through cellular and humoral mechanisms leading to acute or
      chronic rejection, which ultimately results in graft loss. Over the last five
      decades, there have been significant advances in the understanding of the immune
      responses to transplanted organs in both experimental and clinical transplant
      settings. Modulation of the immune response by using immunosuppressive agents has
      led to successful outcomes after kidney transplantation. The paper provides an
      overview of the general organisation and function of human immune system, immune
      response to kidney transplantation, and the current practice of immunosuppressive
      therapy in kidney transplantation in the United Kingdom.

PMID- 29453487
TI  - Significant differences between manufacturer and surgeon in the accuracy of final
      component size prediction with CT-based patient-specific instrumentation for
      total knee arthroplasty.
AB  - PURPOSE: Patient-specific instrumentation (PSI) for total knee arthroplasty (TKA)
      may improve component sizing. Little has been reported about accuracy of the
      default plan created by the manufacturer, especially for CT-based PSI. The goal
      of this study was to evaluate the reliability of this plan and the impact of the
      surgeon's changes on the final accuracy of the guide sizes. METHODS: Forty-five
      patients eligible for primary TKA were prospectively enrolled. The planned
      implant sizes were prospectively recorded from the initial manufacturer's
      proposal and from the final plan adjusted in light of the surgeon's evaluation;
      these two sizes where then compared to the actually implanted sizes. Fisher's
      exact test was used to test differences for categorical variables. Agreement
      between pre-operative plans and final implant was evaluated with the Bland-Altman
      method. RESULTS: The manufacturer's proposal differed from the final implant in 9
      (20.0%) femoral and 23 (51.1%) tibial components, while the surgeon's plan in 6
      (13.3%, femoral) and 12 (26.7%, tibial). Modifications in the pre-operative plan
      were carried out for five (11.1%) femoral and 23 (51.1%) tibial components (p =
      0.03). Appropriate modification occurred in 22 (88.0%) and 19 (76.0%) cases of
      femoral and tibial changes. The agreement between the manufacturer's and the
      surgeon's pre-operative plans was poor, especially with regard to tibial
      components. CONCLUSION: The surgeon's accuracy in predicting the final component
      size was significantly different from that of the manufacturer and changes in the
      initial manufacturer's plan were necessary to get an accurate pre-operative plan
      of the implant sizes. CLINICAL RELEVANCE: Careful evaluation of the initial
      manufacturer's plan by an experienced knee surgeon is mandatory when planning TKA
      with CT-based PSI. LEVEL OF EVIDENCE: II.

PMID- 29453488
TI  - No evidence for combining cartilage treatment and knee osteotomy in
      osteoarthritic joints: a systematic literature review.
AB  - PURPOSE: To assess whether the combination of HTO and cartilage treatment
      produced an additional clinical benefit compared to HTO alone. The secondary aim
      was to identify if there was any difference among different cartilage procedures
      in terms of healing potential and clinical outcome. METHODS: A systematic review
      of the literature was performed on PubMed database by three independent observers
      according to the following inclusion criteria: clinical reports of any level of
      evidence, written in the English language, with no time limitation, about HTO
      associated with cartilage surgical and injective treatment, including surveys
      reporting clinical, radiological, or second-look outcomes at any follow-up time.
      RESULTS: The database search identified 1956 records: 21 studies were included
      for the final analysis, for a total of 1068 patients; 10 case series and 11
      comparative studies. While overall good results were reported in the case series,
      the analysis of the comparative studies showed less uniform results. Among the
      eight studies investigating HTO with cartilage surgical procedures, improved
      tissue regeneration was found in 5/8 studies, whereas a clinical improvement was
      reported only in two studies. Three studies on HTO combination with injective
      treatment showed better tissue regeneration and clinical benefit. CONCLUSIONS:
      Literature presents low-quality studies, with only few heterogeneous comparative
      papers. While surgical treatments targeting only the cartilage layer did not
      achieve clinical improvements, injective treatments targeting the overall joint
      environment showed promising findings. This prompts further research towards the
      development of treatments able to improve knee osteotomies outcomes. However,
      until new evidence will prove otherwise, there is no indication for a combined
      cartilage treatment in routine clinical practice. LEVEL OF EVIDENCE: Level IV.

PMID- 29453489
TI  - Fascia iliaca blockade with the addition of liposomal bupivacaine vs. plain
      bupivacaine for perioperative pain management following hip arthroscopy.
AB  - PURPOSE: A newer formulation of bupivacaine, encapsulated within carrier
      molecules, has garnered attention for its role in providing extended post
      operative analgesia. The purpose was to evaluate the addition of liposomal
      bupivacaine to fascia iliaca blockade during hip arthroscopy. METHODS:
      Retrospective cohort study of patients undergoing hip arthroscopy with a pre
      operative fascia iliaca blockade with either liposomal bupivacaine (Group 1;
      266mg + 20 cc 0.5% plain bupivacaine) or bupivacaine (Group 2; 40 cc 0.25% plain
      bupivacaine). All patients received standardized pre-operative oral pain
      medications. The primary outcome was the defense veteran pain rating scale
      (DVPRS). Secondary outcomes included duration of hospital admission, PACU opioid
      use, PACU pain scores, and duration of nerve blockade. RESULTS: Thirty-eight
      males and 30 females, mean age of 33 years (range 14-56). There was no difference
      in pre-operative DVPRS between the groups (n.s.). There was no difference in post
      operative DVPRS pain scores at POD0 (3.7 vs. 3.9, n.s.), POD1 (4.2 vs. 3.8,
      n.s.), POD2 (4.2 vs. 3.7, n.s.), POD3 (3.9 vs. 3.7, n.s.) or POD14 (2.2 vs. 2.4,
      n.s.). Group 1 trended towards longer mean total hospital admission time (872 vs.
      822 min, n.s.), and greater mean morphine equivalents administered in the PACU
      (33 vs. 29 mg, n.s.). 68% of patients in group 1 reported continued anterior
      thigh numbness at POD3, compared to 34% in group 2 (p = 0.008). CONCLUSIONS:
      Despite the advertised benefits of prolonged post-operative analgesia using
      liposomal bupivacaine, there were no significant differences in post-operative
      pain scores or PACU opioid consumption. Our results support that acceptable pain
      scores are successfully achieved at all time periods with the use of multimodal
      analgesia including fascia iliaca blockade despite the type of pain medication
      administered. LEVEL OF EVIDENCE: III.

PMID- 29453490
TI  - Goal-directed reaching: the allocentric coding of target location renders an
      offline mode of control.
AB  - Reaching to a veridical target permits an egocentric spatial code (i.e., absolute
      limb and target position) to effect fast and effective online trajectory
      corrections supported via the visuomotor networks of the dorsal visual pathway.
      In contrast, a response entailing decoupled spatial relations between stimulus
      and response is thought to be primarily mediated via an allocentric code (i.e.,
      the position of a target relative to another external cue) laid down by the
      visuoperceptual networks of the ventral visual pathway. Because the ventral
      stream renders a temporally durable percept, it is thought that an allocentric
      code does not support a primarily online mode of control, but instead supports a
      mode wherein a response is evoked largely in advance of movement onset via
      central planning mechanisms (i.e., offline control). Here, we examined whether
      reaches defined via ego- and allocentric visual coordinates are supported via
      distinct control modes (i.e., online versus offline). Participants performed
      target-directed and allocentric reaches in limb visible and limb-occluded
      conditions. Notably, in the allocentric task, participants reached to a location
      that matched the position of a target stimulus relative to a reference stimulus,
      and to examine online trajectory amendments, we computed the proportion of
      variance explained (i.e., R2 values) by the spatial position of the limb at 75%
      of movement time relative to a response's ultimate movement endpoint. Target
      directed trials performed with limb vision showed more online corrections and
      greater endpoint precision than their limb-occluded counterparts, which in turn
      were associated with performance metrics comparable to allocentric trials
      performed with and without limb vision. Accordingly, we propose that the absence
      of ego-motion cues (i.e., limb vision) and/or the specification of a response via
      an allocentric code renders motor output served via the 'slow' visuoperceptual
      networks of the ventral visual pathway.

PMID- 29453493
TI  - Altered prepulse inhibition of the acoustic startle response in BDNF-deficient
      mice in a model of early postnatal hypoxia: implications for schizophrenia.
AB  - The brain-derived neurotrophic factor (BDNF) is a major proliferative agent in
      the nervous system. Both BDNF-deficiency and perinatal hypoxia represent
      genetic/environmental risk factors for schizophrenia. Moreover, a decreased BDNF
      response to birth hypoxia was associated with the disease. BDNF expression is
      influenced by neuronal activity and environmental conditions such as hypoxia.
      Thus, it may partake in neuroprotective and reparative mechanisms in acute or
      chronic neuronal insults. However, the interaction of hypoxia and BDNF is
      insufficiently understood and the behavioral outcome unknown. Therefore, we
      conducted a battery of behavioral tests in a classical model of chronic early
      postnatal mild hypoxia (10% O2), known to significantly impair brain development,
      in BDNF-deficient mice. We found selective deficits in measures associated with
      sensorimotor gating, namely enhanced acoustic startle response (ASR) and reduced
      prepulse inhibition (PPI) of ASR in BDNF-deficient mice. Unexpectedly, the
      alterations of sensorimotor gating were caused only by BDNF-deficiency alone,
      whereas hypoxia failed to evoke severe deficits and even leads to a milder
      phenotype in BDNF-deficient mice. As deficits in sensorimotor gating are present
      in schizophrenia and animal models of the disease, our results are of relevance
      regarding the involvement of BDNF in its pathogenesis. On the other hand, they
      suggest that the effect of perinatal hypoxia on long-term brain abnormalities is
      complex, ranging from protective to deleterious actions, and may critically
      depend on the degree of hypoxia. Therefore, future studies may refine existing
      hypoxia protocols to better understand neurodevelopmental consequences associated
      with schizophrenia.

PMID- 29453492
TI  - Application of physiologically based pharmacokinetic modeling to the prediction
      of drug-drug and drug-disease interactions for rivaroxaban.
AB  - PURPOSE: Rivaroxaban is a direct oral anticoagulant with a large inter-individual
      variability. The present study is to develop a physiologically based
      pharmacokinetic (PBPK) model to predict several scenarios in clinical practice.
      METHODS: A whole-body PBPK model for rivaroxaban, which is metabolized by the
      cytochrome P450 (CYP) 3A4/5, 2J2 pathways and excreted via kidneys, was developed
      to predict the pharmacokinetics at different doses in healthy subjects and
      patients with hepatic or renal dysfunction. Hepatic clearance and drug-drug
      interactions (DDI) were estimated by in vitro in vivo extrapolation (IVIVE) based
      on parameters obtained from in vitro experiments. To validate the model, observed
      concentrations were compared with predicted concentrations, and the impact of
      special scenarios was investigated. RESULTS: The PBPK model successfully
      predicted the pharmacokinetics for healthy subjects and patients as well as DDIs.
      Sensitivity analysis shows that age, renal, and hepatic clearance are important
      factors affecting rivaroxaban pharmacokinetics. The predicted fold increase of
      rivaroxaban AUC values when combined administered with the inhibitors such as
      ketoconazole, ritonavir, and clarithromycin were 2.3, 2.2, and 1.3, respectively.
      When DDIs and hepatic dysfunction coexist, the fold increase of rivaroxaban
      exposure would increase significantly compared with one factor alone.
      CONCLUSIONS: Our study using PBPK modeling provided a reasonable approach to
      evaluate exposure levels in special patients under special scenarios. Although
      further clinical study or real-life experience would certainly merit the current
      work, the modeling work so far would at least suggest caution of using
      rivaroxaban in complicated clinical settings.

PMID- 29453491
TI  - Does hearing aid use affect audiovisual integration in mild hearing impairment?
AB  - There is converging evidence for altered audiovisual integration abilities in
      hearing-impaired individuals and those with profound hearing loss who are
      provided with cochlear implants, compared to normal-hearing adults. Still, little
      is known on the effects of hearing aid use on audiovisual integration in mild
      hearing loss, although this constitutes one of the most prevalent conditions in
      the elderly and, yet, often remains untreated in its early stages. This study
      investigated differences in the strength of audiovisual integration between
      elderly hearing aid users and those with the same degree of mild hearing loss who
      were not using hearing aids, the non-users, by measuring their susceptibility to
      the sound-induced flash illusion. We also explored the corresponding window of
      integration by varying the stimulus onset asynchronies. To examine general group
      differences that are not attributable to specific hearing aid settings but rather
      reflect overall changes associated with habitual hearing aid use, the group of
      hearing aid users was tested unaided while individually controlling for
      audibility. We found greater audiovisual integration together with a wider window
      of integration in hearing aid users compared to their age-matched untreated
      peers. Signal detection analyses indicate that a change in perceptual sensitivity
      as well as in bias may underlie the observed effects. Our results and comparisons
      with other studies in normal-hearing older adults suggest that both mild hearing
      impairment and hearing aid use seem to affect audiovisual integration, possibly
      in the sense that hearing aid use may reverse the effects of hearing loss on
      audiovisual integration. We suggest that these findings may be particularly
      important for auditory rehabilitation and call for a longitudinal study.

PMID- 29453494
TI  - Population genetic data of Investigator HDplex markers in Han population from
      Southern China.
AB  - Allele frequencies and forensic statistical parameters for 12 STRs contained in
      the Investigator HDplex Kit (D2S1360, D3S1744, D4S2366, D5S2500, SE33, D6S474,
      D7S1517, D8S1132, D10S2325, D12S391, D18S51, and D21S2055) were estimated from a
      sample of 503 unrelated individuals from the Guangdong Han population of South
      China. No significant departure from the Hardy-Weinberg equilibrium or genetic
      linkage disequilibrium was observed (after Bonferroni correction). The expected
      heterozygosity ranged from 0.6411 to 0.9414. The allele frequencies in Guangdong
      Han significantly differed from that in Shanghai Han, Korea, Northern Italian,
      Swedish, Dutch, Somalia, and Argentinean populations at 2 to 12 loci. The markers
      included in the kit have highly polymorphic information that could be used for
      forensic DNA analysis as potential tools for differentiating Han population from
      other populations in the world.

PMID- 29453495
TI  - Comparison of concentrations of drugs between blood samples with and without
      fluoride additive-important findings for Delta9-tetrahydrocannabinol and
      amphetamine.
AB  - Fluoride is a common stabilizing agent in forensic toxicology to avoid the
      frequent problem of degradation of drugs in blood samples especially described
      for cocaine. In cases only samples with addition of fluoride are available, it is
      a crucial question if also concentrations of common drugs other than cocaine
      (amphetamines, opiates and cannabinoids) are affected by fluoride. So far, there
      are only rare literature data available on discrepant results especially for
      Delta9-tetrahydrocannabinol (THC). In this study, comparative analysis of
      positive tested paired routine plasma/serum samples (n = 375), collected at the
      same time point (one device with and one without fluoride), was carried out with
      special focus on cannabinoids. Samples were measured with validated routine
      liquid chromatography-tandem mass spectrometry methods for THC, 11-hydroxy-THC
      (THC-OH), 11-nor-9-carboxy-THC (THC-COOH), cocaine, benzoylecgonine, ecgonine
      methyl ester, morphine, codeine, amphetamine, methamphetamine, 3,4
      methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, and 3,4
      methylenedioxyethylamphetamine, and results were statistically evaluated. Beside
      the expected stabilization effect on cocaine and the consequently reduced
      concentration of ecgonine methyl ester in fluoride samples, benzoylecgonine was
      elevated compared to respective samples without fluoride. Most importantly, new
      findings were significantly reduced mean concentrations of THC (- 17%), THC-OH (-
      17%), and THC-COOH (- 22%) in fluoride samples. Mean amphetamine concentration
      was significantly higher in samples with the additive (+ 6%). For the other
      amphetamine type of drugs as well as for morphine and codeine, no significant
      differences could be seen. Whenever specified thresholds have been set, such as
      in most European countries, the use of different blood sample systems may result
      in a motorist being differently charged or prosecuted. The findings will support
      forensic toxicologists at the interpretation of results derived from fluoride
      stabilized blood samples.

PMID- 29453496
TI  - Influence of surface treatment on the performance of silorane-based composite
      resin in class I restorations: a randomized clinical trial.
AB  - OBJECTIVES: The aim of this study was to evaluate the clinical performance of
      silorane-based composite restorations applied after different surface treatments.
      MATERIALS AND METHODS: This controlled and randomized clinical trial included 26
      patients with class I restoration indications. The teeth were randomly assigned
      to the following treatments: control 1/G1, silorane specific self-etching
      adhesive (P90 self-etch primer and bond) + silorane-based composite resin
      (FiltekTM P90 low shrink posterior restorative); G2, 37% phosphoric acid +
      silorane specific self-etching adhesive + silorane-based composite resin; G3,
      blasting with aluminum oxide + silorane specific self-etching adhesive + silorane
      based composite resin; and control 2/G4, self-etching adhesive (AdperTM SE Plus
      self-etch adhesive) + dimethacrylate-based composite resin (FiltekTM P60
      posterior restorative). The clinical performance was evaluated at baseline and
      after 1 year. RESULTS: A total of 141 restorations were made and evaluated. For
      all clinical criteria evaluated, no significant difference was found between the
      surface treatments at baseline and after 1 year (p > 0.05). After 1 year, only
      the group with 37% phosphoric acid + silorane specific self-etching adhesive (G2)
      showed a significant reduction in marginal adaptation (p < 0.05). CONCLUSION: In
      general, all surface treatments showed an adequate clinical performance for
      silorane-based composite resin in class I restorations. However, a reduction in
      the marginal adaptation after 1 year was found when additional phosphoric acid
      etching was used prior to silorane specific self-etching adhesive. CLINICAL
      RELEVANCE: The use of phosphoric acid etching prior to specific self-etching
      adhesive can adversely affect the marginal adaptation of silorane-based
      restorations.

PMID- 29453497
TI  - Bone mineralization and vascularization in bisphosphonate-related osteonecrosis
      of the jaw: an experimental study in the rat.
AB  - OBJECTIVES: Pathogenesis of bisphosphonate-related osteonecrosis of the jaws
      (BRONJ) is not fully explained. An antiangiogenic effect of bisphosphonates (BPs)
      or an altered bone quality have been advocated. The aims of the present study
      were to analyze alveolar mandibular vascularization and bone quality in rats with
      BRONJ. MATERIALS AND METHODS: Thirty-eight Sprague-Dawley rats were randomized
      into two groups: zoledronic acid (ZA), n = 27, and control (CTRL) n = 11. The ZA
      group received a weekly IV injection of ZA (100 MUg/kg) during 10 weeks. The CTRL
      group received saline. After 6 weeks, extraction of the right mandibular molars
      was performed. Rats were sacrificed after 14 weeks. Microtomography characterized
      bone lesions and vascularization after injection of a radio-opaque material.
      Raman microspectroscopy evaluated bone mineralization. RESULTS: Fifty-five
      percent of ZA rats presented bone exposure and signs of BRONJ. None sign was
      found at the left hemimandible in the ZA group and in the CTRL group. Vascular
      density appeared significantly increased in the right hemimandibles of the CTRL
      group compared to the left hemimandibles. Vascularization was reduced in the ZA
      group. A significantly increased of the mineral-to-amide ratio was found in the
      alveolar bone of ZA rats by Raman microspectroscopy. CONCLUSIONS: In a rat model
      of BRONJ, microtomography evidenced osteonecrosis in BRONJ. Raman spectroscopy
      showed an increased mineralization. Vascularization after tooth extraction was
      impaired by ZA. CLINICAL RELEVANCE: Prolonged BP administration caused an
      increase in the mineralization and a quantitative reduction of the
      vascularization in the alveolar bone; both factors might be involved
      concomitantly in the BRONJ pathophysiology.

PMID- 29453498
TI  - Seed priming with iron and zinc in bread wheat: effects in germination, mitosis
      and grain yield.
AB  - Currently, the biofortification of crops like wheat with micronutrients such as
      iron (Fe) and zinc (Zn) is extremely important due to the deficiencies of these
      micronutrients in the human diet and in soils. Agronomic biofortification with Fe
      and Zn can be done through different exogenous strategies such as soil
      application, foliar spraying, and seed priming. However, the excess of these
      micronutrients can be detrimental to the plants. Therefore, in the last decade, a
      high number of studies focused on the evaluation of their phytotoxic effects to
      define the best strategies for biofortification of bread wheat. In this study, we
      investigated the effects of seed priming with different dosages (1 mg L-1 to 8 mg
      L-1) of Fe and/or Zn in germination, mitosis and yield of bread wheat cv.
      'Jordao' when compared with control. Overall, our results showed that:
      micronutrient dosages higher than 4 mg L-1 negatively affect the germination; Fe
      and/or Zn concentrations higher than 2 mg L-1 significantly decrease the mitotic
      index and increase the percentage of dividing cells with anomalies; treatments
      performed with 8 mg L-1 of Fe and/or 8 mg L-1 Zn caused negative effects in
      germination, mitosis and grain yield. Moreover, seed priming with 2 mg L-1 Fe + 2
      mg L-1 Zn has been shown to be non-cytotoxic, ensuring a high rate of germination
      (80%) and normal dividing cells (90%) as well as improving tillering and grain
      yield. This work revealed that seed priming with Fe and Zn micronutrients
      constitutes a useful and alternative approach for the agronomic biofortification
      of bread wheat.

PMID- 29453501
TI  - 2018 International Hernia Congress : March 12-15, 2018 Miami, FL.

PMID- 29453499
TI  - Screening for gene-environment (G*E) interaction using omics data from exposed
      individuals: an application to gene-arsenic interaction.
AB  - Identifying gene-environment interactions is a central challenge in the quest to
      understand susceptibility to complex, multi-factorial diseases. Developing an
      understanding of how inter-individual variability in inherited genetic variation
      alters the effects of environmental exposures will enhance our knowledge of
      disease mechanisms and improve our ability to predict disease and target
      interventions to high-risk sub-populations. Limited progress has been made
      identifying gene-environment interactions in the epidemiological setting using
      existing statistical approaches for genome-wide searches for interaction. In this
      paper, we describe a novel two-step approach using omics data to conduct genome
      wide searches for gene-environment interactions. Using existing genome-wide SNP
      data from a large Bangladeshi cohort study specifically designed to assess the
      effect of arsenic exposure on health, we evaluated gene-arsenic interactions by
      first conducting genome-wide searches for SNPs that modify the effect of arsenic
      on molecular phenotypes (gene expression and DNA methylation features). Using
      this set of SNPs showing evidence of interaction with arsenic in relation to
      molecular phenotypes, we then tested SNP-arsenic interactions in relation to skin
      lesions, a hallmark characteristic of arsenic toxicity. With the emergence of
      additional omics data in the epidemiologic setting, our approach may have the
      potential to boost power for genome-wide interaction research, enabling the
      identification of interactions that will enhance our understanding of disease
      etiology and our ability to develop interventions targeted at susceptible sub
      populations.

PMID- 29453500
TI  - Isolated greater tuberosity fractures of the proximal humerus: anatomy, injury
      patterns, multimodality imaging, and approach to management.
AB  - The greater tuberosity is an important anatomic structure and its integrity is
      important for shoulder abduction and external rotation. Isolated fractures of the
      greater tuberosity are often subtle and may not be detected on initial
      radiographs. Clinically, these patients display symptoms which mimic a full
      thickness rotator cuff tear. It is important to differentiate these two entities,
      as their treatment is different (typically nonsurgical management for minimally
      displaced fractures versus rotator cuff repair for acute full thickness rotator
      cuff tears). When greater tuberosity fractures are significantly displaced and
      allowed to heal without anatomic reduction, they can lead to impingement. This
      article will review greater tuberosity anatomy and function, as well as the
      clinical presentation and multimodality imaging findings of greater tuberosity
      fractures. Imaging optimization, pitfalls, and clinical management of these
      fractures will also be discussed.

PMID- 29453502
TI  - Parenting Wisely Six Months Later: How Implementation Delivery Impacts Program
      Effects at Follow-Up.
AB  - We evaluated the effectiveness of the Parenting Wisely (PW) program 6 months post
      intervention and assessed differences based on delivery format. Using a quasi
      experimental design, parents (N = 311) participated in the PW program in one of
      five formats (i.e., parents-only intensive workshop, parents-only 5-week group,
      parents and adolescents 5-week group, parent and adolescent online, and parent
      only online format). An additional 53 parents served as a comparison group. We
      used the McMaster Family Assessment Device, the Child Behavior Checklist, and the
      Violent Behavior Checklist to measure family functioning, parenting, and
      adolescent behavior. Relative to the comparison group, at 6 month follow-up
      parents who participated in PW reported increases in confidence in their
      parenting skills, decreases in conflicts with their adolescents, and decreases in
      adolescent externalizing and violent behavior. Mechanisms of change analyses
      supported the conceptual model that program effects were related to child
      behavior changes by influencing positive parenting and decreasing negative family
      dynamics. PW effectiveness did not vary substantially by delivery format, except
      for the intensive workshop format, which was less effective than other formats.
      These findings extend research on PW to include evidence of sustained program
      effects on adolescent externalizing and violent behaviors in an ethnically
      diverse, socioeconomically disadvantaged sample. Study findings are relevant to
      agencies and clinicians who are seeking to implement an evidence-based, flexible
      parent-training program.

PMID- 29453503
TI  - Monitoring the brain strikes a discordant note for anesthesiologists.

PMID- 29453504
TI  - Financing the Primary Care Behavioral Health Model.
AB  - The PCBH model of integrated care blends behavioral health professionals into the
      primary care team, thereby enhancing the scope of primary care and expanding the
      range of services provided to the patient. Despite promising evidence in support
      of the model and a growing number of advocates and practitioners of PCBH
      integration, current reimbursement policies are not always favorable. As the
      nation's healthcare system transitions to value-based payment models, new
      financing strategies are emerging which will further support the viability of
      PCBH integration. This article provides an overview of the infrastructure
      necessary to support PCBH practice; reviews the current PCBH funding landscape;
      discusses how emerging trends in healthcare financing are impacting the model;
      and provides a vision for the viability of the PCBH model within the value-based
      financing of our healthcare system in the future.

PMID- 29453505
TI  - Does Hope Matter? Associations Among Self-Reported Hope, Anxiety, and Health
      Related Quality of Life in Children and Adolescents with Cancer.
AB  - This study aimed to examine the direct and indirect effects of hope on health
      related quality of life (HRQoL) via anxiety of children/adolescents with cancer.
      We proposed to test if the mediation model was moderated by the
      child/adolescent's treatment status. The participants were 211
      children/adolescents diagnosed with cancer, divided into two clinical groups
      according to treatment status: 97 patients on-treatment and 114 off-treatment.
      Self-reported questionnaires measured the youths' hope, anxiety, and HRQoL
      perceptions. The results revealed that children/adolescents on- and off-treatment
      only differed in levels of HRQoL, with a more compromised HRQoL found for the on
      treatment group. Hope was positively associated with HRQoL, directly and
      indirectly via anxiety reduction. Moreover, only the association between anxiety
      and HRQoL was moderated by clinical group, revealing stronger associations for on
      treatment patients. Findings highlight the importance of hope as a decisive
      resource in pediatric cancer adaptation, which may be strategically targeted in
      psycho-oncological interventions.

PMID- 29453506
TI  - Illness Beliefs, Treatment Beliefs and Information Needs as Starting Points for
      Patient Information: The Evaluation of an Intervention for Patients with
      Depression.
AB  - Patients with depression are often dissatisfied with disease- and therapy-related
      information. The objective of this study was to evaluate an intervention that
      applied the Common Sense Model to the provision of information during inpatient
      rehabilitation for patients with depression. The intervention was evaluated in a
      sequential control group design. Analyses of covariance were used to assess
      differences between the control and intervention groups. Changes with respect to
      illness and treatment beliefs (personal control, treatment control, coherence and
      concerns about medicines), satisfaction with information about medicines, illness
      and rehabilitation, and depressive burden were selected as primary outcome
      measures. We observed significant between-group differences indicating the
      intervention group's superiority in terms of satisfaction with information
      regarding medicines. However, the two groups' changes during rehabilitation did
      not differ in terms of the other outcomes. The intervention resulted in patients
      judging that their medication information needs had been more thoroughly
      fulfilled than those patients who received care-as-usual information. However,
      the intervention did not prove to be effective when the other outcome variables
      are considered. Taken together and bearing in mind the limitations of our study
      particularly the non-randomised design-our results should be replicated in a
      randomised controlled trial.

PMID- 29453507
TI  - Interprofessional Education: Opportunities and Challenges for Psychology.
AB  - This manuscript is an outgrowth of an invited panel presentation at the national
      Association for Psychologists in Academic Health Centers Conference in 2017 on
      Interprofessional Education (IPE). IPE is a structured and transformative
      educational strategy designed to provide active learning experiences where
      trainees from diverse healthcare professions gain shared content knowledge plus
      collaboration skills as they learn about, from, and with each other.
      Collaboration skills include understanding professional role distinctions and
      overlap, effective team-based communication, shared values/ethics and respect for
      each other's expertise, and teamwork dynamics. It is increasingly important to
      expand training beyond the intraprofessional activities in which psychology
      trainees engage to prepare them to participate in interprofessional collaborative
      care. As healthcare systems move to team-based collaborative practice and value
      based reimbursement models, the profession of psychology needs leaders at every
      academic health center to facilitate the design and/or implementation of IPE
      activities. The panel of psychologists presented roles that psychologists play in
      IPE institutional program design and implementation, graduate training programs,
      and the perspectives of an early career psychologist and psychology trainee.
      Opportunities and challenges are highlighted, culminating in a call to action.
      Psychologists must embrace their identity as health professionals and engage
      their learners in IPE so that the emerging cognitive schemata of healthcare that
      is developed includes the profession of psychology. Otherwise, healthcare teams
      and health professionals will not understand the value, roles, or potential
      contributions of psychologists in enhancing patient care outcomes, ultimately
      jeopardizing psychologists' referrals, involvement in healthcare delivery, and
      career opportunities.

PMID- 29453508
TI  - Refractory gastric antral ulcers without Helicobacter pylori infection and non
      steroidal anti-inflammatory drugs.
AB  - Herein, we describe a rare case of refractory gastric antral ulcers. A woman in
      her 50 s was admitted to Nagoya City University Hospital with epigastric pain
      after being diagnosed with gastric antral submucosal tumor at another hospital.
      Findings from esophagogastroduodenoscopy and endoscopic ultrasound examination
      revealed that the lesion was a gastric ulcer. The patient had no Helicobacter
      pylori infection and no recent history of using non-steroidal anti-inflammatory
      drugs. On the basis of these findings, we diagnosed this as a case of refractory
      gastric antral ulcer (RGAU). RGAU is considered a new disease concept and
      detailed analyses are expected in the future.

PMID- 29453509
TI  - Critical thresholds for eventual extinction in randomly disturbed population
      growth models.
AB  - This paper considers several single species growth models featuring a carrying
      capacity, which are subject to random disturbances that lead to instantaneous
      population reduction at the disturbance times. This is motivated in part by
      growing concerns about the impacts of climate change. Our main goal is to
      understand whether or not the species can persist in the long run. We consider
      the discrete-time stochastic process obtained by sampling the system immediately
      after the disturbances, and find various thresholds for several modes of
      convergence of this discrete process, including thresholds for the absence or
      existence of a positively supported invariant distribution. These thresholds are
      given explicitly in terms of the intensity and frequency of the disturbances on
      the one hand, and the population's growth characteristics on the other. We also
      perform a similar threshold analysis for the original continuous-time stochastic
      process, and obtain a formula that allows us to express the invariant
      distribution for this continuous-time process in terms of the invariant
      distribution of the discrete-time process, and vice versa. Examples illustrate
      that these distributions can differ, and this sends a cautionary message to
      practitioners who wish to parameterize these and related models using field data.
      Our analysis relies heavily on a particular feature shared by all the
      deterministic growth models considered here, namely that their solutions exhibit
      an exponentially weighted averaging property between a function of the initial
      condition, and the same function applied to the carrying capacity. This property
      is due to the fact that these systems can be transformed into affine systems.

PMID- 29453510
TI  - Next-generation metabolic screening: targeted and untargeted metabolomics for the
      diagnosis of inborn errors of metabolism in individual patients.
AB  - The implementation of whole-exome sequencing in clinical diagnostics has
      generated a need for functional evaluation of genetic variants. In the field of
      inborn errors of metabolism (IEM), a diverse spectrum of targeted biochemical
      assays is employed to analyze a limited amount of metabolites. We now present a
      single-platform, high-resolution liquid chromatography quadrupole time of flight
      (LC-QTOF) method that can be applied for holistic metabolic profiling in plasma
      of individual IEM-suspected patients. This method, which we termed "next
      generation metabolic screening" (NGMS), can detect >10,000 features in each
      sample. In the NGMS workflow, features identified in patient and control samples
      are aligned using the "various forms of chromatography mass spectrometry (XCMS)"
      software package. Subsequently, all features are annotated using the Human
      Metabolome Database, and statistical testing is performed to identify
      significantly perturbed metabolite concentrations in a patient sample compared
      with controls. We propose three main modalities to analyze complex, untargeted
      metabolomics data. First, a targeted evaluation can be done based on identified
      genetic variants of uncertain significance in metabolic pathways. Second, we
      developed a panel of IEM-related metabolites to filter untargeted metabolomics
      data. Based on this IEM-panel approach, we provided the correct diagnosis for 42
      of 46 IEMs. As a last modality, metabolomics data can be analyzed in an
      untargeted setting, which we term "open the metabolome" analysis. This approach
      identifies potential novel biomarkers in known IEMs and leads to identification
      of biomarkers for as yet unknown IEMs. We are convinced that NGMS is the way
      forward in laboratory diagnostics of IEMs.

PMID- 29453511
TI  - Developing new age-specific prostate-specific antigen thresholds for testing for
      prostate cancer.
AB  - PURPOSE: To examine whether age-related reference ranges for "normal" prostate
      specific antigen (PSA) change (determined in men without prostate cancer) can be
      used to identify men at high risk of having prostate cancer. METHODS: Subjects
      were men aged 50-69 years with PSA < 10 ng/mL from the UK-based Prostate Testing
      for cancer and Treatment (ProtecT) study. Men with prostate cancer were
      categorized as high or low risk of progression (Low risk: Gleason score <= 6 and
      stage T1-T2a; High risk: Gleason score 7-10 or stage T2C). Men without prostate
      cancer were those with no histological confirmation of prostate cancer.
      Previously developed longitudinal reference ranges for normal age-related PSA
      change were used to calculate an age-specific PSA threshold. We compared the
      ability of our age-specific PSA threshold to discriminate between high- and
      no/low-risk prostate cancer with that of two existing thresholds: (i) threshold
      of PSA = 3 ng/ml for all ages; (ii) National Institute of Clinical Excellence
      (NICE) guidelines dependent on age-group thresholds (age 50-59: PSA = 3 ng/mL;
      age 60-70: PSA = 4 ng/mL; age >= 70: PSA = 5 ng/mL). RESULTS: We included 823 men
      with high-risk prostate cancer and 80,721 men with no/low-risk prostate cancer. A
      threshold of PSA = 3 ng/ml for all ages identified more high-risk prostate
      cancers, recommending biopsy in 9.8% of men, of which 10.3% (n = 823) had high
      risk prostate cancer. Using the NICE guidelines as the threshold for biopsy, 6.9%
      men were recommended for biopsy, of which 11.9% (n = 668) had high-risk prostate
      cancer. Using the new age-specific threshold for biopsy, 2.3% men were
      recommended for biopsy, of which 15.2% (n = 290) had high-risk prostate cancer.
      The age-specific threshold identified fewer high-risk prostate cancers, but fewer
      men received unnecessary biopsy. CONCLUSION: There is no benefit to using
      reference ranges for "normal" PSA that change with age nor the age-specific
      thresholds suggested by the NICE guidelines. While the age-varying thresholds are
      more discriminatory, too many high-risk cancers are missed.

PMID- 29453513
TI  - Simultaneous cell disruption and lipid extraction of wet aurantiochytrium sp.
      KRS101 using a high shear mixer.
AB  - Microalgae are regarded as a promising source of biofuels, and the concept of a
      microalgae-based biorefinery has attracted increasing attention in recent years.
      From an economic perspective, however, the process remains far from competitive
      with fossil fuels. This is particularly true of lipid extraction, due in part to
      the energy-intensive drying step. As a result, wet extraction methods have been
      studied as an economic alternative. In the present study, a novel extraction
      approach which utilizes high shear stress mixing was adopted and demonstrated for
      simultaneous lipid extraction and cell disruption to enable the retrieval of
      lipids directly from concentrated wet biomass. When a high shear mixer (HSM) was
      used to extract lipid from a dense biomass (> 350 g/L) of the oleaginous algae
      Aurantiochytrium sp., it exhibited a yield of esterifiable lipids which exceeded
      80% in 10 min at 15,000 rpm with various solvent types. The HSM was found to
      improve the lipid yields substantially with solvents less miscible with either
      lipids or water, such that the range of Hansen solubility parameters for the
      usable solvents became 3.3 times wider (14.9-26.5 MPa1/2). The HSM, which
      appeared effectively to loosen the water barrier that prevents solvent molecules
      from penetrating through the cell envelope, was found to be more efficient with
      hexane, hexane/isopropanol, and ethanol, all of which showed nearly identical
      lipid yields compared to the dry extraction process. The HSM can, indeed, offer a
      powerful mechanical means of lipid extraction with non-polar and less toxic
      solvents from wet biomass.

PMID- 29453512
TI  - Global and Japanese regional variations in radiologist potential workload for
      computed tomography and magnetic resonance imaging examinations.
AB  - PURPOSE: To investigate the global variation in radiologist potential workload
      for CT and MRI examinations, and the regional variation in potential workload and
      extent of radiologists' involvement in CT and MRI examinations in Japan. METHODS:
      "Radiologist potential workload" was defined as the annual number of CT plus MRI
      examinations divided by the total number of diagnostic radiologists. The extent
      of radiologists' involvement was measured as the proportion of CT and MRI
      examinations to which "Added-fees for Radiological Managements on Imaging-studies
      (ARMIs)" were applied among eligible examinations. Maximum variation was computed
      as the ratio of the highest-to-lowest values among the countries or Japanese
      prefectures. RESULTS: The radiologist potential workload in Japan was 2.78-4.17
      times higher than those in other countries. A maximum prefecture-to-prefecture
      variation was 3.88. The average percentage of CT plus MRI examinations with ARMI
      applied was 43.3%, with a maximum prefecture-to-prefecture variation of 3.97.
      Prefectures with more radiologists tended to have a higher extent of
      radiologists' involvement. CONCLUSIONS: Japan had a far greater radiologist
      potential workload compared with other countries, with a large regional variation
      among prefectures. Prefectures with more radiologists tended to have a higher
      extent of radiologists' involvement in CT and MRI examinations.

PMID- 29453514
TI  - Prevalence and Determinants of Vitamin D Deficiency Among the Overweight and
      Obese Singaporeans Seeking Weight Management Including Bariatric Surgery: a
      Relationship with Bone Health.
AB  - PURPOSE: Low vitamin D status is prevalent worldwide and has been linked to a
      variety of pathologies including obesity in adults. The severity of vitamin D
      deficiency amongst the overweight and obese Singaporeans is not well documented.
      The purpose of this prospective observational study was to assess the prevalence
      and determinants of vitamin D deficiency in a multi-ethnic Asian population
      referred for weight management, including those seeking bariatric surgery.
      MATERIALS AND METHODS: This was a cross-sectional study conducted among 111
      consecutive subjects referred to a single institution weight management service
      in Singapore. The data collected included their anthropometric data, body mass
      index (BMI), body fat percentage, waist circumference, 25-hydroxyvitamin D
      [25(OH)D] and other bone turnover markers. RESULTS: The average BMI among the 111
      subjects was 40.1 +/- 8.2 kg/m2 and mean age of 40 +/- 10 years. Vitamin D
      deficiency was found in 75.7% of the population. There was a significant negative
      association of vitamin D with adiposity markers including BMI (r = - 0.31), body
      fat percentage (r = - 0.34) and waist circumference (r = - 0.26). Predictors of
      vitamin D deficiency included age > 50 years, female gender, waist circumference
      and body fat percentage. CONCLUSION: Vitamin D deficiency is prevalent among this
      target population in Singapore regardless of ethnicity. In particular, the
      elderly, females, those with larger waist circumference and body fat percentage
      were significantly associated with lower serum 25(OH)D level. Hence, routine
      screening for the overweight and obese subjects in multi-ethnic Singapore seeking
      weight management is indicated.

PMID- 29453516
TI  - The coiled spring sign of appendiceal intussusception.

PMID- 29453515
TI  - Micro-fragmented adipose tissue injection for the treatment of complex anal
      fistula: a pilot study accessing safety and feasibility.
AB  - BACKGROUND: The aim of the present study was to evaluate the safety and efficacy
      of autologous, micro-fragmented and minimally manipulated adipose tissue
      injection associated closure of the internal opening in promoting healing of
      complex anal fistula. METHODS: A pilot study was conducted on patients referred
      to our center with anal fistula, from April 2015-December 2016. Inclusion
      criteria were age over 16 years old and a diagnosis of complex anal fistula
      according to the American Gastroenterological Association classification The
      patients were divided into 2 groups; the "first time group" (Group I) in which
      micro-fragmented adipose tissue injection with closure of the internal opening
      was the first sphincter-saving procedure, and the "recurrent group" (Group II)
      consisting of patients who had failed prior sphincter-saving procedures. The
      procedure was carried out 4-6 weeks after seton placement. Follow-up visits were
      scheduled at 7 days, and 1, 3, 6 and 12 months after surgery. Fistula healing was
      defined as the closure of the internal and external openings without any
      discharge. RESULTS: Out of 47 patients with complex transsphincteric anal
      fistula, 19 met the inclusion criteria and were selected to undergo the
      procedure. Twelve of these patients (Group I) had micro-fragmented adipose tissue
      injection as first-line treatment, and 7 (Group II) had failed previous sphincter
      saving procedures. The mean operative time was 55 +/- 6 min (range 50-70 min).
      The mean postoperative pain score measured with the visual analog pain scale was
      2 +/- 1.4 (range 0-4). No intraoperative difficulties related to the use of the
      kit were recorded. There were no cases of postoperative fever or abdominal sepsis
      related to the procedure and no post-treatment perianal bleeding or impaired anal
      continence. Only 3 cases of minor abdominal wall hematoma that did not require
      any treatment and 1 case of perianal abscess were observed. Patients were
      evaluated for a mean follow-up time of 9 +/- 3.1 months (range 3-12 months). The
      overall healing rate was 73.7, 83.3% for Group I and 57.1% for Group II.
      CONCLUSIONS: The injection of autologous, micro-fragmented and minimally
      manipulated adipose tissue associated with closure of the internal opening is a
      safe, feasible and reproducible procedure and may enhance complex anal fistula
      healing.

PMID- 29453518
TI  - Chimeric antigen receptors with human scFvs preferentially induce T cell anti
      tumor activity against tumors with high B7H6 expression.
AB  - B7H6 is emerging as a promising tumor antigen that is known to be expressed on a
      wide array of tumors and is reported to stimulate anti-tumor responses from the
      immune system. As such, B7H6 presents a good target for tumor-specific
      immunotherapies. B7H6-specific chimeric antigen receptors (CAR) based on a murine
      antibody showed successful targeting and elimination of tumors expressing B7H6.
      However, mouse single chain variable fragments (scFvs) have the potential to
      induce host anti-CAR responses that may limit efficacy, so human scFvs specific
      for B7H6 were selected by yeast surface display. In this study, we validate the
      functionality of these human scFvs when formatted into chimeric antigen
      receptors. The data indicate that T cells expressing these B7H6-specific human
      scFvs as CARs induced potent anti-tumor activity in vitro and in vivo against
      tumors expressing high amounts of B7H6. Importantly, these human scFv-based CARs
      are sensitive to changes in B7H6 expression which may potentially spare non-tumor
      cells that express B7H6 and provides the foundation for future clinical
      development.

PMID- 29453517
TI  - Probable Diagnosis of a Patient with Niemann-Pick Disease Type C: Managing
      Pitfalls of Exome Sequencing.
AB  - Here, we present a case of a 31-year-old man with progressive cognitive decline,
      ataxia, and dystonia. Extensive laboratory, radiographic, and targeted genetic
      studies over the course of several years failed to yield a diagnosis. Initial
      whole exome sequencing through a commercial laboratory identified several
      variants of uncertain significance; however, follow-up clinical examination and
      testing ruled each of these out. Eventually, repeat whole exome sequencing
      identified a known pathogenic intronic variant in the NPC1 gene (NM_000271.4,
      c.1554-1009G>A) and an additional heterozygous exonic variant of uncertain
      significance in the NPC1 gene (NM_000271.4, c.2524T>C). Follow-up biochemical
      testing was consistent with a diagnosis of probable Niemann-Pick disease Type C
      (NP-C). This case illustrates the potential of whole exome sequencing for
      diagnosing rare complex neurologic diseases. It also identifies several potential
      common pitfalls that must be navigated by clinicians when interpreting commercial
      whole exome sequencing results.

PMID- 29453519
TI  - TriCurin, a synergistic formulation of curcumin, resveratrol, and epicatechin
      gallate, repolarizes tumor-associated macrophages and triggers an immune response
      to cause suppression of HPV+ tumors.
AB  - Our earlier studies reported a unique potentiated combination (TriCurin) of
      curcumin (C) with two other polyphenols. The TriCurin-associated C displays an
      IC50 in the low micromolar range for cultured HPV+ TC-1 cells. In contrast,
      because of rapid degradation in vivo, the TriCurin-associated C reaches only low
      nano-molar concentrations in the plasma, which are sub-lethal to tumor cells.
      Yet, injected TriCurin causes a dramatic suppression of tumors in TC-1 cell
      implanted mice (TC-1 mice) and xenografts of Head and Neck Squamous Cell
      Carcinoma (HNSCC) cells in nude/nude mice. Here, we use the TC-1 mice to test our
      hypothesis that a major part of the anti-tumor activity of TriCurin is evoked by
      innate and adaptive immune responses. TriCurin injection repolarized
      arginase1high (ARG1high), IL10high, inducible nitric oxide synthaselow (iNOSlow),
      IL12low M2-type tumor-associated macrophages (TAM) into ARG1low, IL10low,
      iNOShigh, and IL12high M1-type TAM in HPV+ tumors. The M1 TAM displayed sharply
      suppressed STAT3 and induced STAT1 and NF-kB(p65). STAT1 and NF-kB(p65) function
      synergistically to induce iNOS and IL12 transcription. Neutralizing IL12
      signaling with an IL12 antibody abrogated TriCurin-induced intra-tumor entry of
      activated natural killer (NK) cells and Cytotoxic T lymphocytes (CTL), thereby
      confirming that IL12 triggers recruitment of NK cells and CTL. These activated NK
      cells and CTL join the M1 TAM to elicit apoptosis of the E6+ tumor cells.
      Corroboratively, neutralizing IL12 signaling partially reversed this TriCurin
      mediated apoptosis. Thus, injected TriCurin elicits an M2->M1 switch in TAM,
      accompanied by IL12-dependent intra-tumor recruitment of NK cells and CTL and
      elimination of cancer cells.

PMID- 29453520
TI  - Evaluation of a Comprehensive Oral Health Services Program in School-Based Health
      Centers.
AB  - Objectives In 2011, the Maternal and Child Health Bureau, within the Health
      Resources and Services Administration, awarded a 4-year grant to increase access
      to and assure the delivery of quality oral health preventive and restorative
      services to children. The grant was awarded to organizations serving high-need
      communities through school-based health centers (SBHCs). This article describes
      an independent evaluation investigating program efficacy, integration, and
      sustainability. Methods Program process and outcomes data were gathered from
      interim and final reports. Interviews with key informants were conducted by
      phone, and analyzed in NVivo qualitative software. Results Students had great
      need for comprehensive services: on average, 45% had dental caries at enrollment.
      Enrollment increased from 5000 to more than 9700, and the percent receiving
      preventive services increased from 58 to 88%. Results of the analytically
      weighted linear regression show statistically significant increases in the
      proportion of enrollees who had their teeth cleaned in the past year (t(4) =
      5.19, beta = 8.85, p < 0.05) and those receiving overall preventive services
      (t(4) = 13.52, beta = 10.93, p < 0.01). Grantees integrated into existing
      programs using clear, consistent, and open communication. Grantees sustained the
      full suite of services beyond the grant period by increasing billing and
      insurance claims while still offering free and reduced-cost services to those
      uninsured or otherwise unable to pay. Conclusions for Practice This project
      demonstrates that access to comprehensive oral health care for children can be
      expanded through SBHCs. State Title V Block Grant and other similar federal
      initiatives can learn from the strategic approaches used to overcome challenges
      in the school-based environment.

PMID- 29453521
TI  - Safety and feasibility of breast lesion localization using magnetic seeds
      (Magseed): a multi-centre, open-label cohort study.
AB  - PURPOSE: Wire localization has several disadvantages, notably wire migration and
      difficulty scheduling the procedure close to surgery. Radioactive seed
      localization overcomes these disadvantages, but implementation is limited due to
      radiation safety requirements. Magnetic seeds potentially offer the logistical
      benefits and transcutaneous detection equivalence of a radioactive seed, with
      easier implementation. This study was designed to evaluate the feasibility and
      safety of using magnetic seeds for breast lesion localization. METHODS: A two
      centre open-label cohort study to assess the feasibility and safety of magnetic
      seed (Magseed) localization of breast lesions. Magseeds were placed under
      radiological guidance into women having total mastectomy surgery. The primary
      outcome measure was seed migration distance. Secondary outcome measures included
      accuracy of placement, ease of transcutaneous detection, seed integrity and
      safety. RESULTS: Twenty-nine Magseeds were placed into the breasts of 28 patients
      under ultrasound guidance. There was no migration of the seeds between placement
      and surgery. Twenty-seven seeds were placed directly in the target lesion with
      the other seeds being 2 and 3 mm away. All seeds were detectable transcutaneously
      in all breast sizes and at all depths. There were no complications or safety
      issues. CONCLUSIONS: Magnetic seeds are a feasible and safe method of breast
      lesion localization. They can be accurately placed, demonstrate no migration in
      this feasibility study and are detectable in all sizes and depths of breast
      tissue. Now that safety and feasibility have been demonstrated, further clinical
      studies are required to evaluate the seed's effectiveness in wide local excision
      surgery.

PMID- 29453522
TI  - Structural disconnection is responsible for increased functional connectivity in
      multiple sclerosis.
AB  - Increased synchrony within neuroanatomical networks is often observed in
      neurophysiologic studies of human brain disease. Most often, this phenomenon is
      ascribed to a compensatory process in the face of injury, though evidence
      supporting such accounts is limited. Given the known dependence of resting-state
      functional connectivity (rsFC) on underlying structural connectivity (SC), we
      examine an alternative hypothesis: that topographical changes in SC, specifically
      particular patterns of disconnection, contribute to increased network rsFC. We
      obtain measures of rsFC using fMRI and SC using probabilistic tractography in 50
      healthy and 28 multiple sclerosis subjects. Using a computational model of
      neuronal dynamics, we simulate BOLD using healthy subject SC to couple regions.
      We find that altering the model by introducing structural disconnection patterns
      observed in those multiple sclerosis subjects with high network rsFC generates
      simulations with high rsFC as well, suggesting that disconnection itself plays a
      role in producing high network functional connectivity. We then examine SC data
      in individuals. In multiple sclerosis subjects with high network rsFC, we find a
      preferential disconnection between the relevant network and wider system. We
      examine the significance of such network isolation by introducing random
      disconnection into the model. As observed empirically, simulated network rsFC
      increases with removal of connections bridging a community with the remainder of
      the brain. We thus show that structural disconnection known to occur in multiple
      sclerosis contributes to network rsFC changes in multiple sclerosis and further
      that community isolation is responsible for elevated network functional
      connectivity.

PMID- 29453523
TI  - Digital versus light microscopy assessment of surgical margin status after
      radical prostatectomy.
AB  - Positive surgical margin (PSM) extension reported as focal or non-focal/extensive
      is an important pathologic prognostic parameter after radical prostatectomy.
      Likewise, there is limited or no agreement on how to measure and what the best
      cut-off points to be used in practice are. We hypothesized that digital
      microscopy (DM) would potentially provide a more objective way to measure PSM and
      better define its clinical significance. To further our knowledge, we have
      evaluated PSM status in 107 laparoscopic radical prostatectomies using digital
      and conventional light microscopy (LM). DM evaluation detected three additional
      PSM cases, but no differences were seen (LM vs DM; p = 0.220). Mean linear
      measurement correlated to biochemical recurrence (BR) (LM, p = 0.002; DM, p =
      0.001). ROC analysis identified a cut-off point to assess linear measurement by
      LM (3.5 mm) or DM (3.2 mm), but only digital measurement was significant for BR
      free survival. Our study also evaluated a cut-off <= 3 mm that was associated to
      BR using LM (p = 0.023) or DM (p = 0.001). Finally, the number of paraffin blocks
      bearing PSM correlated with BR (p < 0.001) status with either LM or DM. In
      conclusion, DM produces similar data than LM but shows more accurate
      measurements. Reporting of PSM with score of <= 3 vs. > 3 mm linear extent using
      LM (3.2 mm if digital microscopy is applied) might represent an important
      prognostic feature after radical prostatectomy. Alternatively, reporting the
      number of blocks with PSM 1 vs. 2 or more might also provide important prognostic
      data in practice.

PMID- 29453525
TI  - Correction to: Genetic analysis of multi-environmental spring wheat trials
      identifies genomic regions for locus-specific trade-offs for grain weight and
      grain number.
AB  - Unfortunately, the Fig. 1 of this original article was incorrectly published. The
      corrected Fig. 1 is given below.

PMID- 29453524
TI  - A Nonsteroidal Novel Formulation Targeting Inflammatory and Pruritus-Related
      Mediators Modulates Experimental Allergic Contact Dermatitis.
AB  - INTRODUCTION: A major clinical challenge in treating allergic contact dermatitis
      (ACD) is that the first line of treatment is based on the use of corticosteroids.
      In this study, we aimed to develop a formulation that is devoid of steroids.
      METHODS: We used mouse ears treated with dinitrofluorobenzene (DNFB) to induce
      ACD. The efficacy of the test formulation to ameliorate and to prevent induced
      ACD was determined. RESULTS: To treat this experimentally induced ACD, we
      developed a formulation containing BIPxine (a mixture of Rosa moschata and Croton
      lechleri (antioxidants) and Aloe vera and D-panthenol (moisturizers), and
      hydroglycolic solutions of disodium cromoglycate. Our results show that clear
      inhibition of ACD took place. The target of this formulation was PAR-2, TRPV4,
      and other mediators of the inflammatory and pain responses. However, this
      formulation must be evaluated in other models besides the mouse to confirm its
      effectiveness. CONCLUSION: The formulation presented here may provide new ACD
      therapies that do not involve the use of corticosteroids.

PMID- 29453526
TI  - Characterization of Pm59, a novel powdery mildew resistance gene in Afghanistan
      wheat landrace PI 181356.
AB  - KEY MESSAGE: A new powdery mildew resistance gene, designated Pm59, was
      identified in Afghanistan wheat landrace PI 181356, and mapped in the terminal
      region of the long arm of chromosome 7A. Powdery mildew, caused by Blumeria
      graminis f. sp. tritici (Bgt), is an important foliar disease of wheat worldwide.
      In the Great Plains of the USA, Bgt isolates virulent to widely used powdery
      mildew resistance genes, such as Pm3a, were previously identified. The objectives
      of this study were to characterize the powdery mildew resistance gene in
      Afghanistan landrace PI 181356, which exhibited high resistance to Bgt isolates
      collected in southern Great Plains, and identify molecular markers for marker
      assisted selection. An F2 population and F2:3 lines derived from a cross between
      PI 181356 and OK1059060-126135-3 were used in this study. Genetic analysis
      indicated that PI 181356 carries a single dominant gene, designated Pm59, in the
      terminal region of the long arm of chromosome 7A. Pm59 was mapped to an interval
      between sequence tag site (STS) markers Xmag1759 and Xmag1714 with genetic
      distances of 0.4 cM distal to Xmag1759 and 5.7 cM proximal to Xmag1714. Physical
      mapping suggested that Pm59 is in the distal bin 7AL 0.99-1.00. Pm59 is a novel
      powdery mildew resistance gene, and confers resistance to Bgt isolates collected
      from the Great Plains and the state of Montana. Therefore, Pm59 can be used to
      breed powdery mildew-resistant cultivars in these regions. Xmag1759 is ideal for
      marker-assisted selection of Pm59 in wheat breeding.

PMID- 29453528
TI  - Longitudinal Analysis of Racial/Ethnic Trends in Quality Outcomes in Community
      Health Centers, 2009-2014.
AB  - BACKGROUND: To monitor progress towards eliminating health disparities, community
      health centers have reported on hypertension control, diabetes control, and
      birthweight by race and ethnicity since 2008. OBJECTIVE: To evaluate
      racial/ethnic time trends in quality outcomes in health centers and to assess
      both within- and between-center disparities in outcomes. DESIGN AND SAMPLE: Using
      2009-2014 data from all US health centers (n = 1047 centers, serving 19.6 million
      patients/year), we evaluated racial/ethnic time trends in quality outcomes for
      health centers and assessed within- and between-center disparities. MAIN
      MEASURES: Percentage of patients achieving control of blood pressure < 140/90
      mmHg among hypertensive persons, control of glycosylated hemoglobin <= 9.0% among
      diabetic persons, and birthweight >= 2500 g. All outcomes were reported by
      race/ethnicity. KEY RESULTS: There was no evidence of improved outcomes among
      racial/ethnic subgroups from 2009 to 2014, though electronic health record
      adoption, medical recognition, and insurance coverage rates increased
      substantially. Two exceptions were increased rates of normal birthweight for
      black patients (87.0% to 88.8%, or 0.3 percentage points/year, p = 0.02) and
      decreased rates of diabetes control for white patients (74.2% to 69.5%, or -1.0
      percentage points/year, p < 0.01). Within centers, the largest racial/ethnic
      disparities in 2009 were white/black disparities in hypertension control (8.7
      percentage points, 95% CI 7.4-10.1), white/black disparities in diabetes control
      (3.4 percentage points, 95% CI 2.0-4.7), and white/Hispanic disparities in
      diabetes control (4.4 percentage points, 95% CI 2.8-6.0). All disparities
      remained statistically unchanged from 2009 to 2014. White patients were more
      likely to be seen at a health center in the top performance quintile compared
      with black and Hispanic patients (p < 0.001). CONCLUSIONS: Though quality
      outcomes in health centers continued to compare favorably to other care settings,
      we found no evidence of improved quality or reduced disparities in diabetes
      control, hypertension control, or birthweight from 2009 to 2014. Within- and
      between-center racial/ethnic disparities in quality were evident, and both should
      be targeted in future interventions.

PMID- 29453527
TI  - Effects of 4,9-anhydrotetrodotoxin on voltage-gated Na+ channels of mouse vas
      deferens myocytes and recombinant NaV1.6 channels.
AB  - Molecular investigations were performed in order to determine the major
      characteristics of voltage-gated Na+ channel beta-subunits in mouse vas deferens.
      The use of real-time quantitative PCR showed that the expression of Scn1b was
      significantly higher than that of other beta-subunit genes (Scn2b - Scn4b).
      Immunoreactivity of Scn1b proteins was also detected in the inner circular and
      outer longitudinal smooth muscle of mouse vas deferens. In whole-cell recordings,
      the actions of 4,9-anhydroTTX on voltage-gated Na+ current peak amplitude in
      myocytes (i.e., native INa) were compared with its inhibitory potency on
      recombinant NaV1.6 channels (expressed in HEK293 cells). A depolarizing
      rectangular voltage-pulse elicited a fast and transient inward native INa and
      recombinant NaV1.6 expressed in HEK293 cells (i.e., recombinant INa). The current
      decay of native INa was similar to the recombinant NaV1.6 current co-expressed
      with beta1-subunits. The current-voltage (I-V) relationships of native INa were
      similar to those of recombinant NaV1.6 currents co-expressed with beta1-subunits.
      Application of 4,9-anhydroTTX inhibited the peak amplitude of native INa (K i  =
      510 nM), recombinant INa (K i  = 112 nM), and recombinant INa co-expressed with
      beta1-subunits (K i  = 92 nM). The half-maximal (Vhalf) activation and
      inactivation of native INa values were similar to those observed in recombinant
      INa co-expressed with beta1-subunits. These results suggest that beta1-subunit
      proteins are likely to be expressed mainly in the smooth muscle layers of murine
      vas deferens and that 4,9-anhydroTTX inhibited not only native INa but also
      recombinant INa and recombinant INa co-expressed with beta1-subunits in a
      concentration-dependent manner.

PMID- 29453529
TI  - Toxicity Assessment in the Nanoparticle Era.
AB  - The wide use of engineered nanomaterials in many fields, ranging from biomedical,
      agriculture, environment, cosmetic, urged the scientific community to understand
      the processes behind their potential toxicity, in order to develop new strategies
      for human safety. As a matter of fact, there is a big discrepancy between the
      increased classes of nanoparticles and the consequent applications versus their
      toxicity assessment. Nanotoxicology is defined as the science that studies the
      effects of engineered nanodevices and nanostructures in living organisms. This
      chapter analyzes the physico-chemical properties of the most used nanoparticles,
      the way they enter the living organism and their cytoxicity mechanisms at
      cellular exposure level. Moreover, the current state of nanoparticles risk
      assessment is reported and analyzed.

PMID- 29453530
TI  - Mechanisms of Uptake and Translocation of Nanomaterials in the Lung.
AB  - Nanomaterials are invading our environment due to their increasing use in a very
      broad range of sectors making human exposure foreseeable during the life cycle of
      these materials. Inhalation is one of the most frequent routes of exposure in
      case of unintentional exposure and the small size of nanomaterials allows them to
      reach the deep lung. Understanding the fate and effects of nanomaterials is a
      great challenge for scientists as they exhibit a huge physico-chemical diversity
      that drives their biological reactivity. It is critical to determine the fate of
      nanomaterials at their route of entry in the organism as this will determine
      their local and/or systemic effects. In this review we will describe the
      epithelial barriers and the clearance processes of the respiratory tract. The
      mechanisms involved in the internalization of nanomaterials by respiratory cells
      and their ability to cross the epithelial barrier will be presented, highlighting
      methodologies and the role of the nanomaterial physico-chemical properties.

PMID- 29453531
TI  - Transmucosal Nanoparticles: Toxicological Overview.
AB  - Nanoparticles have specific physicochemical properties different to bulk
      materials of the same composition and such properties make them very attractive
      for commercial and medical applications. Mucoadhesive nanoparticulate dosage
      forms are designed to enable prolonged retention of these nanoparticles at the
      site of application, providing a controlled drug release for improved therapeutic
      outcome. Moreover, drug delivery across the mucosa bypasses the first-pass
      hepatic metabolism and avoids the degradation by gastrointestinal enzymes.
      However, like most new technologies, there is a rising debate concerning the
      possible transmucosal side effects resulting from the use of particles at the
      nano level. In fact, these nanoparticles on entering the body, deposit in several
      organs and may cause adverse biological reactions by modifying the physiochemical
      properties of living matter. Several investigators have found nanoparticles
      responsible for toxicity in different organs. In addition, the toxicity of
      nanoparticles also depends on whether they are persistent or cleared from the
      different organs of entry and whether the host can raise an effective response to
      sequester or dispose of the particles. In contrast to many efforts aimed at
      exploiting desirable properties of nanoparticles for medicine, there are limited
      attempts to evaluate potentially undesirable effects of these particles when
      administered intentionally for medical purposes. This chapter focuses on the
      overview of the mucosal systems, fate of nanoparticles, mechanism of
      nanoparticle's toxicity and the various toxicity issues associated with
      nanoparticles through mucosal routes.

PMID- 29453532
TI  - The Toxicity of Nanoparticles to Human Endothelial Cells.
AB  - The use of nanoparticles (NPs) in commercially available products and as
      biomedicinal materials could lead to increasing contact of human blood vessels
      with NPs, and it is necessary to assess the potential adverse effects of NPs to
      cells lining blood vessels. Of them, endothelial cells (ECs) are of particular
      relevance as they play a crucial role in the regulation of function of blood
      vessels. In this book chapter, I discussed studies that used human ECs to study
      the toxicity and mechanisms of NPs. It has been shown that exposure of human ECs
      to NPs could lead to cytotoxicity, genotoxicity, endothelial activation and
      impaired NO signaling. Oxidative stress and inflammation induced by NPs have been
      suggested as the mechanisms associated with the toxicity of NPs to ECs, and a
      three-tier model has been proposed to explain the association between NP induced
      oxidative stress and toxicity. In recent years, dysfunction of autophagy
      (excessive autophagy induction) has also been suggested as one of the mechanisms
      associated with the toxicity of NPs to human ECs. In the future, it is necessary
      to use human ECs to assess the toxicity of NPs to better understand the potential
      adverse effects of NPs entering circulation.

PMID- 29453533
TI  - The Role of Autophagy in Nanoparticles-Induced Toxicity and Its Related Cellular
      and Molecular Mechanisms.
AB  - In the past decades, nanoparticles have been widely used in industry and
      pharmaceutical fields for drug delivery, anti-pathogen, and diagnostic imaging
      purposes because of their unique physicochemical characteristics such as special
      ultrastructure, dispersity, and effective cellular uptake properties. But the
      nanotoxicity has been raised over the extensive applications of nanoparticles.
      Researchers have elucidated series of mechanisms in nanoparticles-induced
      toxicity, including apoptosis, necrosis, oxidative stress, and autophagy. Among
      upon mechanisms, autophagy was recently recognized as an important cell death
      style in various nanoparticles-induced toxicity, but the role of autophagy and
      its related cellular and molecular mechanisms during nanoparticles-triggered
      toxicity were still confusing. In the chapter, we briefly introduced the general
      process of autophagy, summarized the different roles of autophagy in various
      nanoparticle-treated different in vitro/in vivo models, and deeply analyzed the
      physicochemical and biochemical (cellular and molecular) mechanisms of autophagy
      during nanoparticles-induced toxicity through listing and summarizing
      representative examples. Physicochemical mechanisms mainly include dispersity,
      size, charge, and surface chemistry; cellular mechanisms primarily focus on
      lysosome impairment, mitochondria dysfunction, mitophagy, endoplasmic reticulum
      stress and endoplasmic reticulum autophagy; while molecular mechanisms were
      mainly including autophagy related signaling pathways, hypoxia-inducible factor,
      and oxidative stress. This chapter highlighted the important role of autophagy as
      a critical mechanism in nanoparticles-induced toxicity, and the physicochemical
      and biochemical mechanisms of autophagy triggered by nanoparticles might be
      useful for establishing a guideline for the evaluation of nanotoxicology,
      designing and developing new biosafety nanoparticles in the future.

PMID- 29453534
TI  - Nanoparticles-Caused Oxidative Imbalance.
AB  - Application of nanomaterials in nearly every single branch of industry results in
      their accumulation in both abiotic environment and tissues of living organisms.
      Despite the common use of nanomaterials, we are not able to precisely define
      their toxicity towards humans and surrounding biota. Although we were able to
      determine final effects of chronic exposure to nanoparticles which consist of
      many pathologies such as respiratory diseases, allergies, diseases of
      cardiovascular system, disorders in embryonic life differentiation and growth
      disorders, toxic effects on the immune system and cancers. The most predominantly
      investigated feature of most nanoparticles is their ability to induce oxidative
      stress on cellular level. Imbalance in redox state of cells can lead to various
      malfunctions in their internal metabolism, which in turn can lead to mentioned
      pathologies on the organismal level if the exposure is persistent and spread wide
      enough. Imbalance in redox state translate into production of reactive oxygen
      species in amounts impossible to be scavenged in given time. Many reactive oxygen
      species play crucial role in physiological processes in properly functioning
      cells. It was proven on numerous occasions that abundance of ROS, aside from
      oxidative damage, can lead to more subtle adverse effects tied to disturbances in
      intra- and intercellular signaling pathways. In this chapter we would like to
      address the nanoparticle-induced redox imbalance in cells and its effects.

PMID- 29453535
TI  - Toxicity of Metal Oxide Nanoparticles.
AB  - In the recent times, nanomaterials are used in many sectors of science, medicine
      and industry, without revealing its toxic effects. Thus, it is in urgent need for
      exploring the toxicity along with the application of such useful nanomaterials.
      Nanomaterials are categorized with a particle size of 1-100 nm. They have gained
      increasing attention because of their novel properties, including a large
      specific surface area and high reaction activity. The various fundamental and
      practical applications of nanomaterials include drug delivery, cell imaging, and
      cancer therapy. Nanosized semiconductors have their versatile applications in
      different areas such as catalysts, sensors, photoelectronic devices, highly
      functional and effective devices etc. Metal oxides contribute in many areas of
      chemistry, physics and materials science. Mechanism of toxicity of metal oxide
      nanoparticles can occur by different methods like oxidative stress, co-ordination
      effects, non-homeostasis effects, genotoxicity and others. Factors that affect
      the metal oxide nanoparticles were size, dissolution and exposure routes. This
      chapter will explain elaborately the toxicity of metal oxide nano structures in
      living beings and their effect in ecosystem.

PMID- 29453536
TI  - Relevance of Physicochemical Characterization of Nanomaterials for Understanding
      Nano-cellular Interactions.
AB  - The manufactured nanomaterials (NMs) have specific physicochemical properties
      that confer unique mechanical, optical, electrical and magnetic characteristics
      that are beneficial for biomedical and industrial applications. However, recent
      studies have suggested that such specific physicochemical properties of the NMs
      may define nano-bio interactions thereby determining their toxic potential.One of
      the major concerns about NMs is the potential to induce cancer, suggested by some
      experimental studies, as seen for titanium dioxide nanomaterials or carbon
      nanotubes. To analyze in a short term the carcinogenic properties of a compound,
      genotoxicity assays in mammalian cell lines or animal models are frequently used.
      However, the investigation of the genotoxic properties of NMs has been
      inconclusive, up to date, since divergent results have been reported throughout
      the literature. While trying to understand how the NMs' characteristics may
      encompass increased toxicological effects that harbor uncertainties for public
      health, the use of correlation analysis highlights some physicochemical
      properties that influence the genotoxic potential of these NM.In this chapter, it
      is hypothesized that the different genotoxicity observed in closely related NMs
      may be due to subtle differences in their physicochemical characteristics. The
      present work provides an overview of the studies exploring the correlation
      between physicochemical properties of nanomaterials and their genotoxic effects
      in human cells, with focus on the toxicity of two groups of NMs, titanium dioxide
      nanomaterials and multiwalled-carbon nanotubes. It is suggested that, for
      tackling NMs' uncertainties, the in-depth investigation of the nano-bio
      interactions must be foreseen, where in vitro research must be integrated with in
      vivo and biomonitoring approaches, to cope with the complex dynamic behaviour of
      nanoscale materials.

PMID- 29453537
TI  - Toxicogenomics: A New Paradigm for Nanotoxicity Evaluation.
AB  - The wider applications of nanoparticles (NPs) has evoked a world-wide concern due
      to their possible risk of toxicity in humans and other organisms. Aggregation and
      accumulation of NPs into cell leads to their interaction with biological
      macromolecules including proteins, nucleic acids and cellular organelles, which
      eventually induce toxicological effects. Application of toxicogenomics to
      investigate molecular pathway-based toxicological consequences has opened new
      vistas in nanotoxicology research. Indeed, genomic approaches appeared as a new
      paradigm in terms of providing information at molecular levels and have been
      proven to be as a powerful tool for identification and quantification of global
      shifts in gene expression. Toxicological responses of NPs have been discussed in
      this chapter with the aim to provide a clear understanding of the molecular
      mechanism of NPs induced toxicity both in in vivo and in vitro test models.

PMID- 29453538
TI  - Nickel Oxide Nanoparticles Induced Transcriptomic Alterations in HEPG2 Cells.
AB  - Nickel oxide nanoparticles (NiO-NPs) are increasingly used and concerns have been
      raised on its toxicity. Although a few studies have reported the toxicity of NiO
      NPs, a comprehensive understanding of NiO-NPs toxicity in human cells is still
      lagging. In this study, we integrated transcriptomic approach and genotoxic
      evidence to depict the mechanism of NiO-NPs toxicity in human hepatocellular
      carcinoma (HepG2) cells. DNA damage analysis was done using comet assay, which
      showed 26-fold greater tail moment in HepG2 cells at the highest concentration of
      100 MUg/ml. Flow cytometric analysis showed concentration dependent enhancement
      in intracellular reactive oxygen species (ROS). Real-time PCR analysis of
      apoptotic (p53, bax, bcl2) and oxidative stress (SOD1) genes showed
      transcriptional upregulation. Transcriptome analysis using qPCR array showed over
      expression of mRNA transcripts related to six different cellular pathways. Our
      data unequivocally suggests that NiO-NPs induces oxidative stress, DNA damage,
      apoptosis and transcriptome alterations in HepG2 cells.

PMID- 29453539
TI  - Nanoparticle-Protein Interaction: The Significance and Role of Protein Corona.
AB  - The physico-chemical properties of nanoparticles, as characterized under
      idealized laboratory conditions, have been suggested to differ significantly when
      studied under complex physiological environments. A major reason for this
      variation has been the adsorption of biomolecules (mainly proteins) on the
      nanoparticle surface, constituting the so-called "biomolecular corona". The
      formation of biomolecular corona on the nanoparticle surface has been reported to
      influence various nanoparticle properties viz. cellular targeting, cellular
      interaction, in vivo clearance, toxicity, etc. Understanding the interaction of
      nanoparticles with proteins upon administration in vivo thus becomes important
      for the development of effective nanotechnology-based platforms for biomedical
      applications. In this chapter, we describe the formation of protein corona on
      nanoparticles and the differences arising in its composition due to variations in
      nanoparticle properties. Also discussed is the influence of protein corona on
      various nanoparticle activities.

PMID- 29453540
TI  - Cellular and Molecular Toxicity of Iron Oxide Nanoparticles.
AB  - Iron oxide nanoparticles (ION) have attracted much attention because of their
      particular physico-chemical properties, including superparamagnetism. These
      features make them suitable for many purposes and several interesting biomedical
      applications, such as to increase contrast in magnetic resonance imaging (MRI),
      as drug delivery systems and as hyperthermia agents. However, they have also
      shown to be easily accumulated in diverse tissues and induce toxicity at
      different levels. This chapter reviews the different cellular and molecular
      effects induced by ION reported from in vitro studies with human and non-human
      cell lines. Those effects are mainly dependent on ION type and concentration,
      time of exposure, presence and nature of coating, and cell type evaluated. They
      include decreases in viability, plasmatic membrane disruption, oxidative damage,
      mitochondrial alterations, cell cycle impairments, cytoskeleton disruption, cell
      death, and alterations in cell motility, and in cell integrity. Despite these
      negative effects, the numerous advantages of ION together with their promising
      applications in biomedicine, make it necessary to clearly define their toxicity
      in order to discard potential health risks and to reach optimal benefits of their
      use.

PMID- 29453541
TI  - Detection of DNA Damage Induced by Cerium Dioxide Nanoparticles: From Models to
      Molecular Mechanism Activated.
AB  - This chapter will present an original effort to summarize the relevant data about
      the cyto-genotoxicity induced by cerium dioxide nanoparticles (nanoceria) in
      physiologically (in vivo and in vitro) relevant models. In this way, this chapter
      should be extremely useful to everyone who wants to plan their research and
      publishing their results. Massive application of nanoceria at different fields is
      increasing year after year, and it is urgent to address and discuss their use and
      its safety-related issues. Specifically, the nanoceria are being designed for
      nanomedicine, cosmetics, polishing materials and additives for automotive fuels.
      Their unique properties include the ability to absorb UV radiation, antioxidant
      potential and the rapid exchange of valence between Ce4+ and Ce3+ ions associated
      to oxygen storage. In this chapter, the state of the art regarding the
      physicochemical properties of nanoceria, nanogenotoxicity detected by in vitro
      and in vivo systems and the general aspects in the cyto-genotoxic mechanism of
      nanoceria are summarized. The cyto-genotoxicity will be discussed in terms of
      evaluations by Comet assay, Micronucleus test, DNA damage response and oxidative
      stress detected in cell culture systems and in vivo test. We also described the
      dose dependent cyto-genotoxic effects of nanoceria based on their physical
      chemical nature. Paradoxically, these particles have been characterized as either
      pro-oxidant or anti-oxidant in dependence of microenvironment and physiological
      conditions such as pH. Finally, this chapter will contribute to point out aspects
      of the development of new in vitro and in vivo methodologies to detect cyto
      genotoxic effects of the nanoceria.

PMID- 29453542
TI  - Mechanisms Underlying Neurotoxicity of Silver Nanoparticles.
AB  - The potent antimicrobial properties of nanoparticulate silver (AgNPs) have led to
      broad interest in using them in a wide range of commercial and medical
      applications. Although numerous in vivo and in vitro studies have provided
      evidence of toxic effects, rapid commercialization of AgNP-based nanomaterials
      has advanced without characterization of their potential environmental and health
      hazards. There is evidence that AgNPs can be translocated from the blood to the
      brain, regardless the route of exposure, and accumulate in the brain over time.
      As the brain is responsible for basic physiological functions and controls all
      human activities, it is important to assess the hazardous influence of AgNPs
      released from widely used nanoproducts and possible side effects of AgNP-based
      therapies. A number of studies have suggested that the size, shape and surface
      coating, as well as rates of silver ion release and interactions with proteins
      are the key factors determining the neurotoxicity of AgNPs. AgNPs target
      endothelial cells forming the blood-brain barrier, neurons and glial cells and
      leads finally to oxidative stress-related cell death. In this chapter, we review
      in detail current data on the impact of AgNPs on the central nervous system and
      discuss the possible mechanisms of their neurotoxic effects.

PMID- 29453543
TI  - Toxic and Beneficial Potential of Silver Nanoparticles: The Two Sides of the Same
      Coin.
AB  - Nanotechnology has allowed great changes in chemical, biological and physical
      properties of metals when compared to their bulk counterparts. Within this
      context, silver nanoparticles (AgNPs) play a major role due to their unique
      properties, being widely used in daily products such as fabrics, washing
      machines, water filters, food and medicine. However, AgNPs can enter cells
      inducing a "Trojan-horse" type mechanism which potentially leads to cellular
      autophagy, apoptosis or necrosis. On the other hand, this cytotoxicity mechanism
      can be optimized to develop drug nanocarriers and anticancer therapies. The
      increasing use of these NPs entails their release into the environment, damaging
      ecosystems balance and representing a threat to human health. In this context,
      the possible deleterious effects that these NPs may represent for the biotic and
      abiotic ecosystems components represent an obstacle that must be overcome in
      order to guarantee the safety use of their unique properties.

PMID- 29453544
TI  - Molecular and Cellular Toxicology of Nanomaterials with Related to Aquatic
      Organisms.
AB  - The increasing application of nanomaterials both in commercial and industrial
      products has led their accumulation in the aquatic ecosystem. The rapid
      development and large scale production of nanomaterials in the last few decades
      have stimulated concerns regarding their potential environmental health risks on
      aquatic biota. Inorganic nanoparticles, due to their unique properties and
      associated material characteristics resulted in toxicity of these nanomaterials
      in aquatic organisms. Understanding their novel properties at nanoscale has
      established to be a significant aspect of their toxicity. Unique properties such
      as size, surface area, surface coating, surface charge, aggregation of particles
      and dissolution may affect cellular uptake, molecular response, in vivo
      reactivity and delivery across tissues of living organism. Already lot of
      research in the past three or four decades within the nano-ecotoxicology field
      had been carried out. However, there is not any standard technique yet to assess
      toxicity of nanoparticles (NPs) on different biological systems such as
      reproductive, respiratory, nervous, gastrointestinal systems, and development
      stages of aquatic organisms. Specific toxicological techniques and quantification
      of nanoparticles are vital to establish regulations to control their impact on
      the aquatic organism and their release in the aquatic environment. The main aim
      of this chapter is to critically evaluate the current literature on the toxicity
      of nanomaterials on aquatic organism.

PMID- 29453545
TI  - Cytotoxicity and Physiological Effects of Silver Nanoparticles on Marine
      Invertebrates.
AB  - Silver nanoparticles (AgNPs) incorporation in commercial products is increasing
      due to their remarkable physical and chemical properties and their low cost on
      the market. Silver has been known for a long time to be highly toxic to bacterial
      communities, aquatic organisms, and particularly to marine biota. Strong chloro
      complexes dominate Ag speciation in seawater and facilitate its persistence in
      dissolved form. It has a great impact on marine organisms because low
      concentration of silver can lead to strong bioaccumulation, partly because the
      neutral silver chloro complex (AgCl0) is highly bioavailable. Owing to the fact
      that estuaries and coastal areas are considered as the ultimate fate for AgNPs,
      the study of their toxic effects on marine invertebrates can reveal some
      environmental risks related to nanosilver exposure. In an attempt to reach this
      goal, many invertebrate taxa including mollusks, crustaceans, echinoderms and
      polychaetes have been used as biological models. The main findings related to
      AgNP toxicity and marine invertebrates are summarized hereafter. Some cellular
      mechanisms involving nano-internalization (cellular uptake, distribution and
      elimination), DNA damaging, antioxidant cellular defenses and protein expression
      are discussed. Physiological effects on early stage development, silver metabolic
      speciation, immune response, tissue damaging, anti-oxidant effects and nano
      depuration are also described. Finally, we paid attention to some recent
      interesting findings using sea urchin developmental stages and their cells as
      models for nanotoxicity investigation. Cellular and physiological processes
      characterizing sea urchin development revealed new and multiple toxicity
      mechanisms of both soluble and nano forms of silver.

PMID- 29453546
TI  - A Drosophila Model to Decipher the Toxicity of Nanoparticles Taken Through Oral
      Routes.
AB  - In recent era, nanoparticles (NPs) are widely used in food, medicine and body
      implants. Besides it's wide use being a foreign particle it may have some noxious
      effect on the body. To understand the mechanistic role of NPs toxicity,
      Drosophila appeared to be a superior model organism. Toxicity of several
      nanoparticles were accessed using Drosophila. The NPs, after oral route of
      exposure enter into the gut, crosses the barrier of peritrophic membrane and
      induces apoptosis. The toxicity of NPs within gut resulted in developmental
      delay, with decrease in pupa count, fly hatching along with weight loss. The
      adult fly hatched after nanoparticle treatment shows increasing phenotypic defect
      in various sensory organs as well as in different body parts. Besides phenotypic
      defect some of the nanoparticle results altered behavioural phenotypes like larva
      crawling or adult climbing. Alteration of both phenotypic as well as behavioural
      assay clearly hints that signalling pathway like Notch, Wnt, EGFR etc. get
      affected due to exposure of nanoparticle. Results from various labs prove that
      nanoparticle can mediate developmental defect by altering signalling pathways.
      Since many of the signalling pathways are conserved the effect seen in model
      organisms cannot be overlooked. All the nanoparticles used in food and medicine
      should be modified to nullify the toxic effect before used in food and medicine.

PMID- 29453547
TI  - Using of Quantum Dots in Biology and Medicine.
AB  - Quantum dots are nanoparticles, which due to their unique physical and chemical
      (first of all optical) properties, are promising in biology and medicine. There
      are many ways for quantum dots synthesis, both in the form of nanoislands self
      forming on the surfaces, which can be used as single-photon emitters in
      electronics for storing information, and in the form of colloidal quantum dots
      for diagnostic and therapeutic purposes in living systems. The paper describes
      the main methods of quantum dots synthesis and summarizes medical and biological
      ways of their use. The main emphasis is laid on the ways of quantum dots surface
      modification. Influence of the size and form of nanoparticles, charge on the
      surfaces of quantum dots, and cover type on the efficiency of internalization by
      cells and cell compartments is shown. The main mechanisms of penetration are
      considered.

PMID- 29453548
TI  - [Big data from clinical routine].
AB  - BACKGROUND: Over the past 100 years, evidence-based medicine has undergone
      several fundamental changes. Through the field of physiology, medical doctors
      were introduced to the natural sciences. Since the late 1940s, randomized and
      epidemiological studies have come to provide the evidence for medical practice,
      which led to the emergence of clinical epidemiology as a new field in the medical
      sciences. Within the past few years, big data has become the driving force behind
      the vision for having a comprehensive set of health-related data which tracks
      individual healthcare histories and consequently that of large populations.
      OBJECTIVES: The aim of this article is to discuss the implications of data-driven
      medicine, and to examine how it can find a place within clinical care. MATERIALS
      AND METHODS: The EU-wide discussion on the development of data-driven medicine is
      presented. RESULTS: The following features and suggested actions were identified:
      harmonizing data formats, data processing and analysis, data exchange, related
      legal frameworks and ethical challenges. For the effective development of data
      driven medicine, pilot projects need to be conducted to allow for open and
      transparent discussion on the advantages and challenges. The Federal Ministry of
      Education and Research ("Bundesministerium fur Bildung und Forschung," BMBF)
      Arthromark project is an important example. Another example is the Medical
      Informatics Initiative of the BMBF. DISCUSSION AND CONCLUSION: The digital
      revolution affects clinic practice. Data can be generated and stored in
      quantities that are almost unimaginable. It is possible to take advantage of this
      for development of a learning healthcare system if the principles of medical
      evidence generation are integrated into innovative IT-infrastructures and
      processes.

PMID- 29453549
TI  - The German REACH Congress 2016: a workshop report.
AB  - In October 2016, the German REACH Congress was held at the German Federal
      Institute for Risk Assessment (BfR) in Berlin. Here, the associated improvement
      made in the fields of consumer protection and the progress in and experiences
      gained from the implementation of the authorisation procedure were discussed.
      Several speakers from EU institutions, German authorities, industry, and civil
      society organisations were invited to present their views. There was a shared
      consensus that REACH contributes to the advancement of consumer protection
      against chemical risks, mainly because more and higher quality information on
      substance-related hazards and potential exposures becomes available. In addition,
      risk management measures, particularly regarding restrictions on uses, scale down
      consumer exposures to chemicals. Opportunities for improvements identified at the
      congress include the quality of registration dossiers and the management of and
      communication on substances of very high concern (SVHC) that may be present in
      consumer articles. Although regarded as being in an early implementation phase,
      the authorisation process was generally found to be operational and progressing
      well. Criticism was expressed with regard to the consistency of authorisation
      decisions and the costs and uncertainties related to authorisation applications.
      Consumer protection legislation consists of several legal provisions which are
      interlinked. The congress participants agreed that REACH is an important element
      of this legal framework as it enhances and complements other legal provisions.

PMID- 29453550
TI  - Reviewer's comment concerning "Classification of normal sagittal spine alignment:
      refounding the Roussouly classification" by F. Laouissat et al. (2017).
      doi:10.1007/s00586-017-5111-x (Epub ahead of print).

PMID- 29453551
TI  - Characterization of HIV Recent Infection Among High-Risk Men at Public STI
      Clinics in Mumbai.
AB  - We examined associations with HIV recent infection and estimated transmitted drug
      resistance (TDR) prevalence among 3345 men at sexually transmitted infection
      clinics in Mumbai (2002-2005). HIV seroincidence was 7.92% by the BED-CEIA and
      was higher at a clinic located near brothels (12.39%) than at a hospital-based
      clinic (3.94%). HIV recent infection was associated with a lifetime history of
      female sex worker (FSW) partners, HSV-2, genital warts, and gonorrhea. TDR
      prevalence among recent infection cases was 5.7%. HIV testing services near sex
      venues may enhance case detection among high-risk men who represent a bridging
      population between FSWs and the men's other sexual partners.

PMID- 29453552
TI  - HIV-Related Stigma, Social Support, and Psychological Distress Among Individuals
      Initiating ART in Ethiopia.
AB  - Recent World Health Organization HIV treatment guideline expansion may facilitate
      timely antiretroviral therapy (ART) initiation. However, large-scale success of
      universal treatment strategies requires a more comprehensive understanding of
      known barriers to early ART initiation. This work aims to advance a more
      comprehensive understanding of interrelationships among three known barriers to
      ART initiation: psychological distress, HIV-related stigma, and low social
      support. We analyzed cross-sectional interview data on 1175 adults initiating ART
      at six HIV treatment clinics in Ethiopia. Experience of each form of HIV-related
      stigma assessed (e.g., anticipatory, internalized, and enacted) was associated
      with increased odds of psychological distress. However, among those who reported
      enacted HIV-related stigma, there was no significant association between social
      support and psychological distress. Interventions to improve mental health among
      people living with HIV should consider incorporating components to address
      stigma, focusing on strategies to prevent or reduce the internalization of
      stigma, given the magnitude of the relationship between high internalized stigma
      and psychological distress. Interventions to increase social support may be
      insufficient to improve the mental health of people living with HIV who
      experienced enacted HIV-related stigma. Future research should examine
      alternative strategies to manage the mental health consequences of enacted HIV
      related stigma, including coping skills training.

PMID- 29453553
TI  - [Microbiome, atopic eczema and blockade of type 2 immunity].
AB  - Atopic dermatitis affects roughly 20% of children and 3% of adults in Germany and
      other industrial countries, with an increasing prevalence. Its causality has
      still not been conclusively clarified but a type-2 T-helper cell mediated
      immunity reaction (type 2 immunity) dominates cutaneous inflammation. In the
      quest for the underlying pathogenic mechanisms and the development of improved
      prevention and treatment options, attention is also increasingly being paid to
      the influence of microbial colonization. This is facilitated by the rapid
      development of microbial analysis by sequencing. An increasing number of studies
      have shown that there is a link between disorders of the skin microbiome and the
      occurrence of atopic eczema and some also point towards the intestinal
      microbiome. In particular, a loss of diversity regarding the composition of the
      microbiome has been observed.

PMID- 29453554
TI  - In vitro studies of DNA damage and repair mechanisms induced by BNCT in a poorly
      differentiated thyroid carcinoma cell line.
AB  - Boron neutron capture therapy (BNCT) for aggressive tumors is based on nuclear
      reaction [10B (n, alpha) 7Li]. Previously, we demonstrated that BNCT could be
      applied for the treatment of undifferentiated thyroid carcinoma. The aim of the
      present study was to describe the DNA damage pattern and the repair pathways that
      are activated by BNCT in thyroid cells. We analyzed gammaH2AX foci and the
      expression of Ku70, Rad51 and Rad54, main effector enzymes of non-homologous end
      joining (NHEJ) and homologous recombination repair (HRR) pathways, respectively,
      in thyroid follicular carcinoma cells. The studied groups were: (1) C [no
      irradiation], (2) gamma [60Co source], (3) N [neutron beam alone], (4) BNCT
      [neutron beam plus 10 ug 10B/ml of boronphenylalanine (10BPA)]. The total
      absorbed dose was always 3 Gy. The results showed that the number of nuclear
      gammaH2AX foci was higher in the gamma group than in the N and BNCT groups (30
      min-24 h) (p < 0.001). However, the focus size was significantly larger in BNCT
      compared to other groups (p < 0.01). The analysis of repair enzymes showed a
      significant increase in Rad51 and Rad54 mRNA at 4 and 6 h, respectively; in both
      N and BNCT groups and the expression of Ku70 did not show significant differences
      between groups. These findings are consistent with an activation of HRR mechanism
      in thyroid cells. A melanoma cell line showed different DNA damage pattern and
      activation of both repair pathways. These results will allow us to evaluate
      different blocking points, to potentiate the damage induced by BNCT.

PMID- 29453555
TI  - Evaluation of the effect of hyperthermia and electron radiation on prostate
      cancer stem cells.
AB  - The aim of this study was to investigate the effect of hyperthermia, 6 MeV
      electron radiation and combination of these treatments on cancer cell line DU145
      in both monolayer culture and spheroids enriched for prostate cancer stem cells
      (CSCs). Flowcytometric analysis of the expression of molecular markers
      CD133+/CD44+ was carried out to determine the prostate CSCs in cell line DU145
      grown as spheroids in serum-free medium. Following monolayer and spheroid
      culture, DU145 cells were treated with different doses of hyperthermia, electron
      beam and combination of them. The survival and self-renewing of the cells were
      evaluated by colony formation assay (CFA) and spheroid formation assay (SFA).
      Flowcytometry results indicated that the percentage of CD133+/CD44+ cells in
      spheroid culture was 13.9-fold higher than in the monolayer culture. The SFA
      showed significant difference between monolayer and spheroid culture for
      radiation treatment (6 Gy) and hyperthermia (60 and 90 min). The CFA showed
      significantly enhanced radiosensitivity in DU145 cells grown as monolayer as
      compared to spheroids, but no effect of hyperthermia. In contrast, for the
      combination of radiation and hyperthermia the results of CFA and SFA showed a
      reduced survival fraction in both cultures, with larger effects in monolayer than
      in spheroid culture. Thus, hyperthermia may be a promising approach in prostate
      cancer treatment that enhances the cytotoxic effect of electron radiation.
      Furthermore, determination and characterization of radioresistance and
      thermoresistance of CSCs in the prostate tumor is the key to develop more
      efficient therapeutic strategies.

PMID- 29453556
TI  - Effects of increasing dietary protein supplies on milk yield, milk composition,
      and nitrogen use efficiency in lactating buffalo.
AB  - Nitrogen efficiency of lactating buffalo can be increased by providing dietary
      crude protein (CP) precisely to the requirement. Twelve lactating Nili-Ravi
      buffaloes (6 primiparous and 6 multiparous) at 76 +/- 37.5 days in milk (DIM)
      were used in this study. The treatments were diets providing three levels of CP
      (% DM basis): (1) low-protein = 11%; (2) medium-protein = 13.1%; (3) high-protein
      = 14.2% according to a 3 * 3 Latin square design. The period length of each
      treatment was 21 days and the total duration of experiment was 63 days. The diets
      were designed to provide similar energy. The nitrogen intake of buffalo increased
      linearly by increasing CP levels. Dry matter intake showed a tendency toward
      decrease in quadratic fashion, whereas milk yield decreased linearly in high
      protein diet. No effect was observed on milk protein yield and content.
      Increasing the dietary CP levels increased plasma urea nitrogen, whereas glucose
      and triacylglycerol levels remain unaffected. Efficiency of dietary nitrogen
      utilization to milk averaged 21% and showed both linear and quadratic decreases
      by increasing the protein supply levels. In conclusion, low CP level showed
      higher milk production with low plasma urea nitrogen and high nitrogen efficiency
      in this experiment.

PMID- 29453557
TI  - A framework for regional primary health care to organise actions to address
      health inequities.
AB  - OBJECTIVES: Regional primary health-care organisations plan, co-ordinate, and
      fund some primary health-care services in a designated region. This article
      presents a framework for examining the equity performance of regional primary
      health-care organisations, and applies it to Australian Medicare Locals (funded
      from 2011 to 2015). METHODS: The framework was developed based on theory,
      literature, and researcher deliberation. Data were drawn from Medicare Local
      documents, an online survey of 210 senior Medicare Local staff, and interviews
      with 50 survey respondents. RESULTS: The framework encompassed equity in
      planning, collection of equity data, community engagement, and strategies to
      address equity in access, health outcomes, and social determinants of health.
      When the framework was applied to Medicare Locals, their inclusion of equity as a
      goal, collection of equity data, community engagement, and actions improving
      equity of access were strong, but there were gaps in broader advocacy, and
      strategies to address social determinants of health, and equity in quality of
      care. CONCLUSIONS: The equity framework allows a platform for advancing knowledge
      and international comparison of the health equity efforts of regional primary
      health-care organisations.

PMID- 29453560
TI  - Establishment of Primary Culture of Sertoli Cells.
AB  - The successful isolation and culture of Sertoli cells depend on a series of
      delicate processes of mechanical isolation and enzymatic digestion of the
      testicular tissue, taking advantage of an array of enzymes (such as DNAse,
      collagenase, and pancreatin) in order to digest the extracellular matrix
      components. The complexity of these processes may present some differences
      depending on the origin of the testicular sample (whole tissue or biopsy) and of
      the species in question. Rat and mouse Sertoli cells are obtained by a similar
      protocol, whereas bovine and human Sertoli cells require a more extensive
      mechanical and enzymatic processing.

PMID- 29453559
TI  - Regulation of H+-pyrophosphatase by 14-3-3 Proteins from Arabidopsis thaliana.
AB  - Plant vacuolar H+-transporting inorganic pyrophosphatase (V-PPase; EC 3.6.1.1) is
      a crucial enzyme that exists on the tonoplast to maintain pH homeostasis across
      the vacuolar membrane. This enzyme generates proton gradient between cytosol and
      vacuolar lumen by hydrolysis of a metabolic byproduct, pyrophosphate (PP i ). The
      regulation of V-PPase at protein level has drawn attentions of many workers for
      decades, but its mechanism is still unclear. In this work, we show that AVP1, the
      V-PPase from Arabidopsis thaliana, is a target protein for regulatory 14-3-3
      proteins at the vacuolar membrane, and all twelve 14-3-3 isoforms were analyzed
      for their association with AVP1. In the presence of 14-3-3nu, -u, -omicron, and 
      iota, both enzymatic activities and its associated proton pumping of AVP1 were
      increased. Among these 14-3-3 proteins, 14-3-3 u shows the highest stimulation on
      coupling efficiency. Furthermore, 14-3-3nu, -u, -omicron, and -iota exerted
      protection of AVP1 against the inhibition of suicidal substrate PP i at high
      concentration. Moreover, the thermal profile revealed the presence of 14-3
      3omicron improves the structural stability of AVP1 against high temperature
      deterioration. Additionally, the 14-3-3 proteins mitigate the inhibition of Na+
      to AVP1. Besides, the binding sites/motifs of AVP1 were identified for each 14-3
      3 protein. Taken together, a working model was proposed to elucidate the
      association of 14-3-3 proteins with AVP1 for stimulation of its enzymatic
      activity.

PMID- 29453558
TI  - Inorganic nanoparticles in diagnosis and treatment of breast cancer.
AB  - Nanoparticles are being actively developed for biomolecular profiling of cancer
      biomarkers, tumor imaging in vivo, and targeted drug delivery. These
      nanotechnology-based techniques can be applied widely in the management of
      different malignant diseases, such as breast cancer. Although the number of
      different types of nanoparticles is increasing rapidly, most can be classified
      into two major types: particles that contain organic molecules as a major
      building material (such as dendrimers, micelles, liposomes and carbon nanotubes,
      and other polymers); and those that use inorganic elements, usually metals, as a
      core. In particular, inorganic nanoparticles have received increased attention in
      the recent past as potential diagnostic and therapeutic systems in the field of
      oncology. This review primarily discusses progress in applications of inorganic
      nanoparticles for breast cancer imaging and treatment.

PMID- 29453561
TI  - Evaluation of the Purity of Sertoli Cell Primary Cultures.
AB  - The purity of the primary cultures of Sertoli cells is a factor for the
      validation of the studies using this methodological approach. There is a
      probability of contamination of these cultures with other testicular cellular
      types, such as peritubular cells and germ cells (that represent a large
      percentage of the volume of the seminiferous tubules).For the evaluation of the
      purity of cultures, the immunocytochemistry technique (immunoperoxidase or
      immunofluorescence) is frequently used to label a protein marker specific for the
      Sertoli cells within the testicular environment. The expression of several
      protein markers can be used, with different particularities, being that vimentin
      is often used as a marker for Sertoli cells. Vimentin is expressed independently
      of the differentiation state of the cells and is observed around the nuclei and
      in the cytoplasm of Sertoli cells.

PMID- 29453562
TI  - Preparation of Testicular Samples for Histology and Immunohistochemistry.
AB  - One approach to visualize internal structures of the testis is histological
      sectioning of the material. The use of testicular samples allows a detailed
      analysis of the structure of both seminiferous tubules and the interstitial
      space. It is worth noting that key role in the control of germ cell development
      is assigned to Sertoli cells. Thus, in this chapter the special reference is made
      on visualization of Sertoli cells in the seminiferous epithelium in which they
      create a specialized microenvironment to support the germ cell development
      through the formation of the blood-testis barrier (BTB). The use of transmission
      electron microscopy (TEM) allows a deeper insight into the BTB morphology,
      especially the organization of the basal ectoplasmic specialization (ES) and
      coexisting intercellular junctions.Equally important, immunohistochemistry (IHC)
      is an appropriate technique to detect the localization of various proteins in
      paraffin-embedded and fixed tissues, i.e. testicular samples. A proper fixation
      allows to stabilize structure of the seminiferous tubules and preserve cells
      against irreversible damage. As such localization of various junction proteins
      connecting adjoined Sertoli cells and present in germ cell-Sertoli cell
      interfaces is possible. Also immunofluorescence (IF) is helpful to detect the
      distribution and relative abundance of the junctional proteins, while
      immunocytochemistry (ICC) is a valuable technique to show a protein distribution
      within a single cell (e.g. in Sertoli cell culture).

PMID- 29453563
TI  - Rabbit Sertoli Cells: Immunohistochemical Profile from Neonatal to Adult Age.
AB  - Immunohistochemistry (IHC) on formalin-fixed paraffin-embedded tissue specimens
      is a widely used laboratory technique that allows the demonstration and the
      direct microscopical observation of antigens within tissue sections by means of
      specific antibodies. IHC is one the best tools to define the immunophenotype of a
      cell during maturation or neoplastic transformation.To investigate the
      immunophenotype of postnatal rabbit Sertoli cell, from neonatal to adult age, in
      this chapter, the immunohistochemical protocol described is one of the most
      common: the avidin-biotin complex (ABC) method.

PMID- 29453564
TI  - Identification of Proliferative and Apoptotic Sertoli Cells Using Fluorescence
      and Confocal Microscopy.
AB  - Sertoli cells, the testicular somatic cells of the seminiferous epithelium, are
      vital for the survival of the epithelium. They undergo proliferation and
      apoptosis during fetal, neonatal, and prepubertal development. Apoptosis is
      increased in certain situations such as exposure to many substances, for example,
      toxics, or short photoperiod in the non-breeding season of some mammals.
      Therefore, it has always been considered that Sertoli cells that reach adulthood
      are quiescent cells, that is to say, nonproliferative, do not die, are terminally
      differentiated, and whose numbers remain constant. Recently, a degree of both
      proliferation and apoptosis has been observed in normal adult conditions,
      suggesting that consideration of this cell as quiescent may be subject to change.
      All this make it necessary to use histochemical techniques to demonstrate whether
      Sertoli cells are undergoing proliferation or apoptosis in histological sections
      and to allow the qualitative and quantitative study of these. In this chapter, we
      present two double-staining techniques that can be used for identifying Sertoli
      cells in proliferation or apoptosis by fluorescence microscopy. In both, the
      Sertoli cells are identified by an immunohistochemistry for vimentin followed by
      an immunohistochemistry for PCNA or a TUNEL histochemistry.

PMID- 29453565
TI  - Sertoli Cell Preparation for Co-immunoprecipitation.
AB  - Most techniques to study protein-protein interactions, gene expression or signal
      transduction, among others, in Sertoli cells, depend on obtaining a protein
      extract of such cells. This is accomplished by lysing the Sertoli cells and
      solubilizing the intracellular proteins. Depending on the purpose of your study,
      the technique used to lyse and consequently obtain protein extracts from Sertoli
      cells must be considered. In this chapter, we will focus on how to obtain a
      protein Sertoli cell extract suitable for co-immunoprecipitation technique.

PMID- 29453566
TI  - Profiling Signaling Proteins in Sertoli Cells by Co-immunoprecipitation.
AB  - Sertoli cells are crucial for germ cell support, create a suitable environment
      for spermatogenesis, and integrate information from the nervous system and germ
      cell line. To fully understand the role of Sertoli cells, it is necessary to
      characterize the protein-protein interactions. Identifying the interactome of a
      given protein may provide leads about the role and molecular mechanism of such
      protein in Sertoli cells. One of the techniques to characterize protein
      interactomes consists of co-immunoprecipitation followed by mass spectrometry or
      Western blot. Co-immunoprecipitation enables the isolation of a protein target
      and interactome under physiological conditions. In this chapter, we described how
      to perform an interactomic study using the co-immunoprecipitation technique in
      Sertoli cells. Moreover, we will focus on how to analyze and interpret the
      results of a co-immunoprecipitation before mass spectrometry analysis.

PMID- 29453567
TI  - Phagocytosis by Sertoli Cells: Analysis of Main Phagocytosis Steps by Confocal
      and Electron Microscopy.
AB  - Sertoli cells were discovered in the seminiferous tubules by Enrico Sertoli in
      1865 (Morgagni 7:31-33, 1865). Intense phagocytosis is, in the context of
      spermatogenesis cycle, morphologically the most noticeable function of Sertoli
      cells. In this chapter the major principles of phagocytosis machinery and its
      specificities in the seminiferous tubules will be briefly reviewed, guidelines of
      analysis of main phagocytosis steps by confocal and transmission electron
      microscopy will be described, and a simplified method to assess phagocytosis rate
      in routine experiments will be given.

PMID- 29453569
TI  - Assessing Autophagy in Sertoli Cells.
AB  - Autophagy is an important cellular homeostatic process, it degrades most long
      lived proteins and some organelles by lysosome to provide raw materials for the
      survival of the cells during nutrient or energy deprivation condition. Autophagy
      is active in Sertoli cells and involved in many cellular processes. However, the
      precise role of autophagy in Sertoli cells is still largely unknown. Thus, the
      assessment of autophagy in Sertoli cells should be helpful for investigating the
      functional roles of autophagy in Sertoli cells. This chapter describes some
      methods for assessing autophagy in Sertoli cells, including detection of LC3
      maturation/aggregation, transmission electron microscopy, half-life assessments
      of long-lived proteins, immunofluorescence microscopy, and co-localization of
      autophagy-targeted proteins with autophagy components or lysosomal proteins.

PMID- 29453568
TI  - A Method for In Vivo Induction and Ultrastructural Detection of Mitophagy in
      Sertoli Cells.
AB  - An emerging body of evidences based on in vitro studies indicate that mitophagy
      (selective autophagic clearance of damaged mitochondria) is a prosurvival
      mechanism, specifically under exposure to various stressors. Sertoli cells (SCs)
      play essential roles in maintenance of spermatogenesis via paracrine interactions
      with germ cells and other somatic cells in the testis; however, studies
      investigating mitophagy in SCs are still very few. In this chapter, we give a
      brief review of mechanisms and detection methods of mitophagy in SCs based on our
      recent publications on animal models of ethanol toxicity and current literature.
      In addition, we provide a method for induction and ultrastructural identification
      of mitophagy in SCs of adult Wistar rats using a single intraperitoneal injection
      (5 g/kg) of ethanol. Proper understanding of mitophagy features and mechanisms in
      SCs may have therapeutic implications for infertility associated with alcoholism
      and other diseases characterized by mitochondrial dysfunction.

PMID- 29453570
TI  - Molecular Mechanisms and Signaling Pathways Involved in the Nutritional Support
      of Spermatogenesis by Sertoli Cells.
AB  - Sertoli cells play a central role in spermatogenesis. They maintain the blood
      testis barrier, an essential feature of seminiferous tubules which creates the
      proper environment for the occurrence of the spermatogenesis. However, this
      confinement renders germ cells almost exclusively dependent on Sertoli cells'
      nursing function and support. Throughout spermatogenesis, differentiating sperm
      cells become more specialized, and their biochemical machinery is insufficient to
      meet their metabolic demands. Although the needs are not the same at all
      differentiation stages, Sertoli cells are able to satisfy their needs. In order
      to maintain the seminiferous tubule energetic homeostasis, Sertoli cells react in
      response to several metabolic stimuli, through signaling cascades. The AMP
      activated kinase, sensitive to the global energetic status; the hypoxia-inducible
      factors, sensitive to oxygen concentration; and the peroxisome proliferator
      activated receptors, sensitive to fatty acid availability, are pathways already
      described in Sertoli cells. These cells' metabolism also reflects the whole-body
      metabolic dynamics. Metabolic diseases, including obesity and type II diabetes
      mellitus, induce changes that, both directly and indirectly, affect Sertoli cell
      function and, ultimately, (dys)function in male reproductive health. Insulin
      resistance, increased estrogen synthesis, vascular disease, and pubic fat
      accumulation are examples of metabolic-related conditions that affect male
      fertility potential. On the other hand, malnutrition can also induce negative
      effects on male sexual function. In this chapter, we review the molecular
      mechanisms associated with the nutritional state and male sexual (dys)function
      and the central role played by the Sertoli cells.

PMID- 29453571
TI  - Assessing Sertoli Cell Metabolic Activity.
AB  - Nuclear magnetic resonance (NMR)-based metabolomics is widely used in the
      research of metabolic conditions of complex biological systems under various
      conditions, and its use has been found in the field of male fertility. Here we
      describe the implementation of total and targeted NMR-based metabolomics in the
      research on Sertoli cell metabolism. Main principles and techniques of cell
      medium, cellular extracts, and intact cells are explained, as well as some
      classical experiments that can give complementary information on the Sertoli cell
      metabolism.

PMID- 29453572
TI  - Proteome Profiling of Sertoli Cells Using a GeLC-MS/MS Strategy.
AB  - Proteomics is a technology that allows to decipher the molecular networks
      involved in the regulation of biological processes such as spermatogenesis.
      Sertoli cells (SCs) are key players in the paracrine control of this process.
      Envisioning to increase the knowledge on the molecular networks harbored in SCs,
      we propose a methodology based on GeLC-MS/MS for the characterization of these
      cells' proteome. Proteins are separated by SDS-PAGE hyphenated to HPLC and
      identified by mass spectrometry. The integration of data with bioinformatics
      tools such as ClueGO + CluePedia from Cytoscape allows the identification of the
      biological pathways more prevalent in SCs, and that might be modulated by
      pathophysiological conditions. Moreover, the proteome analysis with tools as
      SignalP/SecretomeP highlights the proteins more prone to be secreted and involved
      in the paracrine control of germ cells, which might also be deregulated by
      diseases.

PMID- 29453573
TI  - Gene Silencing of Human Sertoli Cells Utilizing Small Interfering RNAs.
AB  - Sertoli cells, as the unique somatic cells within the seminiferous tubules, play
      essential roles in regulating normal spermatogenesis. In addition, recent studies
      have demonstrated that Sertoli cells could have significant applications in
      regenerative medicine due to their great plasticity. However, the roles of genes
      in controlling the fate determinations of human Sertoli cells remain largely
      unknown. Silencing genes of human Sertoli cells utilizing small interfering RNAs
      (siRNAs) is an important method to explore their functions and mechanisms in
      human Sertoli cells. We isolated and identified human Sertoli cells. RNA
      interference (RNAi) was employed to probe the roles and signaling pathways of
      BMP6 and BMP4 in mediating the proliferation and apoptosis of human Sertoli
      cells. Specifically, siRNAs against BMP6 and BMP4 were used to knock down the
      expression levels of BMP6 and BMP4 and examine the function and mechanism in
      controlling the fate decisions of human Sertoli cells. In this chapter, we
      provided the detailed methods of RNAi in silencing BMP6 gene of human Sertoli
      cells. Quantitative real-time PCR demonstrated that the designed BMP6 siRNAs
      apparently silenced BMP6 mRNA in human Sertoli cells at 24 h after transfection.
      Western blots showed that the siRNAs silenced the expression of BMP6 protein
      effectively at 48 h after transfection. In summary, siRNAs can effectively and
      specifically knock down targeting genes at both transcriptional and translational
      levels utilizing RNAi in human Sertoli cells.

PMID- 29453574
TI  - Testicular Cell Selective Ablation Using Diphtheria Toxin Receptor Transgenic
      Mice.
AB  - Testis development and function is regulated by intricate cell-cell cross talk.
      Characterization of the mechanisms underpinning this has been derived through a
      wide variety of approaches including pharmacological manipulation, transgenics,
      and cell-specific ablation of populations. The removal of all or a proportion of
      a specific cell type has been achieved through a variety of approaches. In this
      paper, we detail a combined transgenic and pharmacological approach to ablate the
      Sertoli or germ cell populations using diphtheria toxin in mice. We describe the
      key steps in generation, validation, and use of the models and also describe the
      caveats and cautions necessary. We also provide a detailed description of the
      methodology applied to characterize testis development and function in models of
      postnatal Sertoli or germ cell ablation.

PMID- 29453575
TI  - Regulation of Blood-Testis Barrier (BTB) Dynamics, Role of Actin-, and
      Microtubule-Based Cytoskeletons.
AB  - The blood-testis barrier (BTB) is an important ultrastructure in the testis that
      supports meiosis and postmeiotic spermatid development since a delay in the
      establishment of a functional Sertoli cell barrier during postnatal development
      in rats or mice by 17-20 day postpartum (dpp) would lead to a delay of the first
      wave of meiosis. Furthermore, irreversible disruption of the BTB by toxicants
      also induces infertility in rodents. Herein, we summarize recent findings that
      BTB dynamics (i.e., disassembly, reassembly, and stabilization) are supported by
      the concerted efforts of the actin- and microtubule (MT)-based cytoskeletons. We
      focus on the role of two actin nucleation protein complexes, namely, the Arp2/3
      (actin-related protein 2/3) complex and formin 1 (or the formin 1/spire 1
      complex) known to induce actin nucleation, respectively, by conferring plasticity
      to actin cytoskeleton. We also focus on the MT plus (+)-end tracking protein
      (+TIP) EB1 (end-binding protein 1) which is known to confer MT stabilization.
      Furthermore, we discuss in particular how the interactions of these proteins
      modulate BTB dynamics during spermatogenesis. These findings also yield a novel
      hypothetical concept regarding the molecular mechanism that modulates BTB
      function.

PMID- 29453577
TI  - Computational Methods Involved in Evaluating the Toxicity of the Reproductive
      Toxicants in Sertoli Cell.
AB  - The Sertoli cell, the somatic component of seminiferous tubule, provides
      nutritional support and immunological protection and supports overall growth and
      division of germ cells. Cytoskeletons, junction proteins, and kinases in Sertoli
      cells are prime targets for reproductive toxicants and other environmental
      contaminants. Among the varied targets, the kinases that are crucial for
      regulating varied activities in spermatogenesis such as assembly/disassembly of
      blood-testis barrier and apical ES and those that are involved in conferring
      polarity are highly targeted. In an attempt to study the effect of toxicants on
      these kinases, the present chapter deals with computational methodology
      concerning their three-dimensional structure prediction, identification of
      inhibitors, and understanding of conformational changes induced by these
      inhibitors.

PMID- 29453576
TI  - Monitoring the Integrity of the Blood-Testis Barrier (BTB): An In Vivo Assay.
AB  - The blood-testis barrier is a unique ultrastructure in the mammalian testis,
      located near the basement membrane of the seminiferous tubule that segregates the
      seminiferous epithelium into the basal and the adluminal (apical) compartment.
      Besides restricting paracellular and transcellular passage of biomolecules (e.g.,
      paracrine factors, hormones), water, electrolytes, and other substances including
      toxicants and/or drugs to enter the adluminal compartment of the epithelium, the
      BTB is an important ultrastructure that supports spermatogenesis. As such, a
      sensitive and reliable assay to monitor its integrity in vivo is helpful for
      studying testis biology. This assay is based on the ability of an intact BTB to
      exclude the diffusion of a small molecule such as sulfo-NHS-LC-biotin
      (C20H29N4NaO9S2, Mr. 556.59, a water-soluble and membrane-impermeable
      biotinylation reagent) from the basal to the apical compartment of the
      seminiferous epithelium. Herein, we summarize the detailed procedures on
      performing the assay and to obtain semiquantitative data to assess the extent of
      BTB damage when compared to positive controls, such as treatment of rats with
      cadmium chloride (CdCl2) which is known to compromise the BTB integrity.

PMID- 29453578
TI  - A Stopped-Flow Light Scattering Methodology for Assessing the Osmotic Water
      Permeability of Whole Sertoli Cells.
AB  - Movement of water into and out of the cell is fundamental to life. In the male
      reproductive tract, at the level of the seminiferous epithelium, Sertoli cells
      are pivotal in mediating the movement of water into the luminal compartment, a
      process providing a means of transport of spermatozoa into the epididymal ducts.
      Here, we describe a stopped-flow light-scattering methodology to easily assess
      the Sertoli cell osmotic water permeability. The devised methodology is well
      suited for studying how the Sertoli cell's permeability changes following
      exogenous stimuli.

PMID- 29453579
TI  - Cryopreservation of Human Testicular Tissue by Isopropyl-Controlled Slow
      Freezing.
AB  - Tissue cryopreservation uses very low temperatures to preserve structurally
      intact living cells in their natural microenvironment. Cell survival is strongly
      influenced by the biophysical effects of ice during both the freezing and the
      subsequent thawing. These effects can be controlled by optimizing the fragment
      size, type of cryoprotectant, and cooling rate. The challenge is to determine
      cryopreservation parameters that suit all cell types present in the tissue. Here
      we describe a quick and convenient protocol for the cryopreservation of
      testicular tissue using an isopropyl-insulated freezing device, which was
      validated in both a mouse and a human model.

PMID- 29453580
TI  - Neurosurgical management of hydrocephalus by a general surgeon in an extremely
      low resource setting: initial experience in North Kivu province of Eastern
      Democratic Republic of Congo.
AB  - PURPOSE: Evaluate the management of hydrocephalus in pediatric patients in the
      Eastern Democratic Republic of Congo by a general surgeon. METHODS: Retrospective
      review of a single institution in the province of North Kivu. Patient charts and
      surgical notes were reviewed from 2003 to 2016. RESULTS: 116 procedures were
      performed for an average of 8.9 per year. 51.7% of surgeries were on female
      patients with an average age of 13.6 +/- 22.7. The average distance traveled from
      home to hospital was 153.7 km but ranged from 5 to 1420 km. The majority of
      hydrocephalus was due to neonatal sepsis (57%); 33.6% were classified as
      congenital; 9.5% of cases followed myelomeningocele closure. 97.4% had a
      ventriculoperitoneal (VP) shunt placed. Endoscopic third ventriculostomy combined
      choroid plexus cauterization (ETV/CPC) was performed in 2.5% of patients. Shunt
      infection occurred in 9.5% of patients, shunt dysfunction or obstruction in 5.2%
      and shunt exteriorization in 1.7%; no complications occurred in patients who
      underwent ETV/CPC. CONCLUSION: VP shunt is the predominant management for
      hydrocephalus in this environment with increasing use of ETV/CPC. Further
      research is needed to evaluate variability by etiology, short and long-term
      outcomes of procedures performed by neurosurgeons and general surgeons, and
      regional epidemiologic variability.

PMID- 29453581
TI  - Health-related quality of life in children born with congenital diaphragmatic
      hernia.
AB  - PURPOSE: The aim of this study was to examine health-related quality of life
      (HRQoL) in children born with congenital diaphragmatic hernia (CDH). METHODS:
      Between 1993 and 2003, a total of 102 children born with CDH were treated at
      Astrid Lindgren Children's hospital in Stockholm. In 2012, long-term survivors (n
      = 77) were asked to participate in the present study, which resulted in a 46% (n
      = 35) response rate. The KIDSCREEN-52 questionnaire was used for measuring HRQoL
      and a detailed review of medical records was performed. RESULTS: The study
      participants did not differ from the non-participants in terms of prenatal
      diagnosis, gender, side of lesion, method of surgical repair, time to intubation,
      need for ECMO support, or way of discharge from the hospital. Children born with
      CDH considered themselves to have a good HRQoL, as good as healthy Swedish
      children. There were only a few significant HRQoL differences within the group of
      children with CDH, although several median scores in ECMO-treated patients were
      somewhat lower. Correlations between child and parent scores on HRQoL were low.
      CONCLUSIONS: Health-related quality of life in children born with CDH is good
      overall, however, a correlation between the severity of the malformation and
      HRQoL cannot be excluded.

PMID- 29453582
TI  - The clinical phenotype of patients positive for antibodies to myositis and
      myositis-related disorders.
AB  - Inflammatory myopathies are a clinically diverse group of diseases, in which the
      detection of particular autoantibodies may facilitate diagnosis, treatment, and
      prognosis. The aim of this report is to summarize our experience with specific
      autoantibody testing in patients with inflammatory myopathies. Data were
      collected over the last decade in the Autoimmune Center of the Sheba Medical
      Center, a tertiary referral hospital. Data regarding patients' positive for
      autoantibodies against Jo-1, PL-7, PL-12, SRP, Mi-2, Ku, and PM-Scl antigens were
      retrospectively collected. Patient demographics, clinical characteristics, and
      mortality were recorded. Descriptive statistics (mean, standard deviation,
      frequency, and percentage) were calculated. A total of 507 patients were surveyed
      for sclero-poly-synthetase antibodies, as part of the diagnostic workup of
      myositis/myalgia or interstitial lung disease. Forty-three patients were found
      positive for one or more of the abovementioned antibodies, and 23 of them
      (53.49%) had interstitial lung disease (ILD). Four patients were positive for
      anti-PL-7, three of them had ILD and Raynaud's phenomenon. Five patients were
      positive for anti-Ku, and four of them had both arthritis and Raynaud's
      phenomenon. Nine patients were positive for anti-Mi-2, and six of them were given
      diagnosed with dermatomyositis. Ten patients were positive for anti-SRP, and six
      of them had cancers of various types. Our results reiterate the previously
      recognized associations between anti-Mi-2 and dermatomyositis, anti-Ku and
      Raynaud's phenomenon, and between anti-PL-7 and ILD. In addition, our data
      support an association between anti-SRP autoantibody positivity and malignancy,
      which calls for further investigation.

PMID- 29453583
TI  - Reconstruction for chronic Achilles tendinopathy: comparison of flexor hallucis
      longus (FHL) transfer versus V-Y advancement.
AB  - BACKGROUND: Several operative techniques exist for Achilles tendinopathy. The
      purpose of our study was to compare the clinical and functional outcomes of
      flexor hallucis longus (FHL) transfer and V-Y advancement for the treatment of
      chronic insertional Achilles tendinopathy. METHODS: Retrospective chart review
      from 2010 to 2016 of patients that underwent FHL transfer or V-Y advancement for
      chronic insertional Achilles tendinopathy. Outcome measures were compared for
      these two procedures. RESULTS: In total, 46 patients (49 ankles) with a mean age
      of 55.0 (range 33-73) years. Mean follow-up time 44.7 +/- 25.5 months. FHL group
      had 21 patients (21 ankles) with 89% satisfaction, 14% complication rate, final
      VAS of 0.4, final VISA-A of 89.1, subjective strength improvement following
      surgery of 78%, and 94% would recommend the procedure. V-Y group had 25 patients
      (28 ankles) with 74% subjective satisfaction, 21% complication rate, final VAS of
      1.4, final VISA-A of 78.4, subjective strength improvement following surgery of
      67%, and 84% would recommend the procedure. There was no significant difference
      in any of the results rates between the two groups (p > .05). CONCLUSION: V-Y
      advancement is comparable to FHL transfer for the operative management of
      insertional Achilles tendinopathy. Though our results trend towards less
      satisfactory results following V-Y advancement, we found high satisfaction rates
      with similar functional outcomes and complication rates in both operative groups.
      We suggest considering V-Y advancement as a viable option for the primary
      treatment of chronic insertional Achilles tendinopathy in patients who may not be
      an ideal candidate for FHL transfer.

PMID- 29453584
TI  - Variations in the attachments of the medial meniscal anterior horn: a descriptive
      cadaveric study.
AB  - PURPOSE: Meniscal tears are common in Kenya, with prevalence rates ranging from
      45 to 78% of intracapsular knee pathology. Diagnosis of these injuries relies on
      the use of both clinical signs and symptoms as well as radiological
      investigations. In a few instances, radiological detection could be difficult,
      partly because of variant attachment patterns of the medial meniscal anterior
      horn. Some of these unusual attachments of the anterior horn of the medial
      meniscus could even be mistaken for meniscal tears. There is also evidence that
      these variations differ from population to population. This study, therefore,
      aimed to determine the variant bony and ligamentous attachments of the medial
      meniscal anterior horn in a sample Kenyan population. METHODS: The study was
      conducted at the Department of Human Anatomy, University of Nairobi. Thirty-one
      male and female unpaired medial menisci were obtained from cadaveric specimen.
      The bony and ligamentous attachments were identified and recorded and
      photomacrographs taken. RESULTS: The bony attachments different from the
      classical textbook attachment accounted for 54.8% of the medial meniscal anterior
      horns. The anterior intermeniscal ligament was present in 62.3% while 16.2%
      showed attachment to the anterior cruciate ligament. Twenty-nine percent (29%) of
      the medial menisci studied did not have any ligamentous attachments. CONCLUSIONS:
      The bony and ligamentous attachments of the medial meniscal anterior horn are
      highly variable presenting unique diagnostic and therapeutic challenges. A new
      classification of ligamentous attachments is thus proposed.

PMID- 29453585
TI  - Predicting hospital length of stay and short-term function after hip or knee
      arthroplasty: are both performance and comorbidity measures useful?
AB  - PURPOSE: Variations in hospital length of stay (LOS) and function are present
      after hip or knee arthroplasty. Comorbidity and performance measures have been
      associated with post-operative outcomes. It is however not known if both
      independently contribute to outcome prediction. The objective of this study was
      to evaluate the combined predictive ability of comorbidity scores (American
      Society of Anesthesiologists classification system (ASA), Charlson comorbidity
      index (CCI), 2008 version of the CCI (CCI08)) and a performance measure (Timed-Up
      and-Go (TUG)) on LOS and short-term function in patients undergoing knee or hip
      arthroplasty. METHODS: One hundred eight patients undergoing hip or knee
      arthroplasty were assessed preoperatively with the ASA, CCI, CCI08, and TUG. LOS
      was determined through administrative data. The Older Americans Resources and
      Services ADL questionnaire (OARS) was used to assess function two and six weeks
      after surgery. Logistic regression was used to assess the relationship between
      pre-operative assessments and LOS and OARS scores. RESULTS: Both the ASA and TUG
      significantly contributed to LOS prediction. Odds ratio (OR) was 3.57 (95%
      confidence interval (CI) 1.26-10.07) for the ASA, and 2.18 (95% CI 1.67-4.15) for
      a one-standard deviation (SD) increase of 4.45 s of the TUG. Only the TUG was
      predictive of two weeks function and trending towards significance for six weeks
      function. One SD TUG increase yielded an OR of 2.14 (95% CI 1.53-3.79) for two
      week function. CONCLUSIONS: The TUG and ASA can be used pre-operatively in
      combination to predict LOS, and TUG can also be used to predict short-term post
      operative function.

PMID- 29453586
TI  - Three-dimensional orientation and location-dependent varying rules of
      radiographic angles of the acetabular cup.
AB  - AIM: The aim of this study is to demonstrate the varying rules of radiographic
      angles following varying three-dimensional (3D) orientations and locations of cup
      using an accurate mathematical model. METHODS: A cone model is established to
      address the quantitative relationship between the opening circle of cup and its
      ellipse projection on radiograph. The varying rules of two-dimensional (2D)
      radiographic anteversion (RA) and inclination (RI) angles can be analyzed.
      RESULTS: When the centre of cup is located above X-ray source, with proper 3D
      RI/RA angles, 2D RA angle can be equal to its 3D counterpart, and 2D RI angle is
      usually greater than its 3D counterpart. Except for the original point on hip
      centered anterior-posterior radiograph, there is no area on radiograph where both
      2D RA and RI angles are equal to their 3D counterparts simultaneously.
      DISCUSSION: This study proposes an innovative model for accurately explaining how
      2D RA/RI angles of cup are varying following different 3D RA/RI angles and
      location of cup. The analysis results provide clinicians an intuitive grasp of
      knowledge about 2D RA/RI angles greater or smaller than their 3D counterparts
      post-operatively. The established model may allow determining the effects of
      pelvic rotations on 2D radiographic angles of cup.

PMID- 29453587
TI  - Trimorphic extreme clubfoot deformities and their management by triple surgical
      skin expanders- DOLAR, DOLARZ and DOLARZ-E (evidence based mega-corrections
      without arthrodesis).
AB  - AIM/PURPOSE: Extreme congenital club foot deformities are common in developing
      countries, presenting at birth, persisting in children, adolescents and adults;
      as untreated/under-corrected by conservative and/or surgical means. Scores of
      confusing names exist in literature for such deformities with no good treatment
      available; mostly advocating unacceptable arthrodesis. The author researched this
      grey area for more than 40 years and successfully innovated improved surgical
      corrections, more acceptable to patients. METHODS: All were given a generic name:
      "extreme deformities", with 3 hierarchic grades. each 3D (trimorphic) because of
      their common aim: a good correction. The author started with anatomical
      dissections in clubfeet (zero cost), consistently reinforced with solid clinical
      background. Heterogeneous skin contractures, congenital with/without scars, were
      discovered as the primary cause with cramped deeper tissues and evolved, evidence
      based, 3D enlargement of skin chamber by triple expanding incisions: DOrso
      LAteral Rotation skin flap (DOLAR- acronym) for grade I, DOLAR + Z-plasty
      (DOLARZ) for grade II and DOLAR + Z + VY-plasty (DOLARZ-E) for grade III, E means
      Extended. Patient satisfaction level (excellent, good, fair/poor) had been
      considered for grading results, rather than scoring systems because each clubfoot
      is different with countless variables. RESULTS & CONCLUSIONS: The author operated
      1080 feet during the last 40 years with long term follow up, six months to 30
      years, with an average of 121/2 years. The results obtained were: excellent/good
      (96%) and fair/poor (4% including superficial skin necrosis only in 3%, evidence
      based). Triple surgical skin expansion consistently resulted in longer, flexible,
      joints sparing, good shaped, better functioning foot; even in adults.

PMID- 29453588
TI  - Problem and Pathological Gambling in Schizophrenia: Exploring Links with
      Substance Use and Impulsivity.
AB  - High rates of both problem and pathological gambling (PPG) and substance-use
      disorders (SUDs) have been reported in schizophrenia, and yet PPG frequently goes
      undetected in clinical practice and unexamined in research. Here, we aimed to
      examine the relationship between PPG and SUDs in a large sample of patients
      across several factors related to both gambling and substance use, including poly
      substance use. Additionally, delay discounting is a form of impulsivity known to
      positively associate with both PPG and SUDs and thought to underlie mechanisms of
      addiction in both contexts. We aimed to investigate the relationship between PPG
      and delay discounting in schizophrenia. 337 individuals with schizophrenia
      completed structured face-to-face interviews regarding gambling behaviors,
      substance use, and delay discounting. PPG in schizophrenia was associated with
      substance use, in particular with poly-substance use, and with delay discounting
      among males. Factors related to substance use were strongly linked with gambling
      in this sample, but not always with PPG more than recreational gambling. Our
      findings overall support the notions that multiple forms of gambling in
      schizophrenia are clinically relevant, that gambling may share common substrates
      with substance use, and that delay discounting represents a potential mechanism
      of this association in males.

PMID- 29453590
TI  - Attribution of weight regain to emotional reasons amongst European adults with
      overweight and obesity who regained weight following a weight loss attempt.
AB  - PURPOSE: Despite the wide availability of effective weight loss programmes,
      maintenance of weight loss remains challenging. Difficulties in emotion
      regulation are associated with binge eating and may represent one barrier to long
      term intervention effectiveness in obesity. The purpose of this study was to
      determine the relationship between emotion regulation difficulties and the extent
      of weight regain in a sample of adults who had lost, and then regained, weight,
      and to examine the characteristics associated with emotional difficulties.
      METHODS: 2000 adults from three European countries (UK, Portugal, and Denmark)
      completed an online survey assessing self-reported weight loss and regain
      following their most recent weight loss attempt. They also completed a binge
      eating disorder screening questionnaire and, if they had regained weight, were
      asked if they attributed it to any emotional factors (a proxy for emotion
      regulation difficulties). Spearman's correlations and logistic regression were
      used to assess the associations between emotion regulation, weight regain, and
      strategy use. RESULTS: Emotion regulation difficulties were associated with
      greater weight regain (N = 1594 who lost and regained weight). Attribution to
      emotional reasons was associated with younger age, female gender, loss of control
      and binge eating, lower perceptions of success at maintenance, using more dietary
      and self-regulatory strategies in weight loss, and fewer dietary strategies in
      maintenance. CONCLUSIONS: Weight-related emotion regulation difficulties are
      common amongst regainers and are associated with regaining more weight. Affected
      individuals are already making frequent use of behavioural strategies during
      weight loss, but do not apply these consistently beyond active attempts. Simply
      encouraging the use of more numerous strategies, without concurrently teaching
      emotion regulation skills, may not be an effective means to improving weight
      outcomes in this group. LEVEL OF EVIDENCE: Level V, descriptive (cross-sectional)
      study.

PMID- 29453591
TI  - Emotional intelligence, empathy and alexithymia in anorexia nervosa during
      adolescence.
AB  - PURPOSE: Socio-emotional difficulties have been observed on adult patients
      suffering from anorexia nervosa (AN). But researches with adolescents are scarce
      and non-congruent. The aim of this paper is to identify the socio-emotional
      difficulties that are encountered by AN during adolescence, and to isolate them
      from those encountered by control adolescents. METHOD: 41 AN and 38 control
      adolescents were assessed using the emotional quotient inventory by Bar-On, youth
      version (EQ-i: YV), the Toronto Alexithymia Questionnaire (TAS-20), the
      Interpersonal Reactivity Index (IRI), and anxiety and depression were controlled
      using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Personal
      distress remains the main difference between the two groups, even when depression
      and anxiety are controlled. Intrapersonal difficulties are observed in the AN
      group, as well as alexithymic traits. CONCLUSION: Research on AN has to focus on
      the socio-emotional difficulties during adolescence, to properly identify which
      difficulties are linked to that life period, and which are a trait of AN. LEVEL
      III: Evidence obtained from well-designed cohort or case-control analytic
      studies, preferably from more than one center or research group.

PMID- 29453589
TI  - Validity of triglyceride-glucose index as an indicator for metabolic syndrome in
      children and adolescents: the CASPIAN-V study.
AB  - PURPOSE: The purpose of this study was to determine the cut-off values of
      triglycerides and glucose (TyG) index as one of the indirect indices for
      metabolic syndrome (MetS) in a pediatric population. METHODS: This national study
      was conducted in 2015 on 14400 students, aged 7-18 years. They were selected by
      random cluster sampling from 30 provinces of our country during the fifth survey
      of a national school-based surveillance program. MetS was defined based on the
      Adult Treatment Panel III (ATP III) criteria modified for the pediatric age
      group. The cut-off values of TyG index for MetS were obtained using the receiver
      operation characteristic (ROC) curve analysis by gender and age groups. RESULTS:
      Totally, 3843 students (52.3% boys) with mean (SD) age of 12.45 (3.04) years were
      assessed. The area under the ROC curve of TyG index for MetS was 0.83 in total
      participants. According to the ATP III criteria the cut-off values of the TyG
      index were 8.33 (8.21-8.45) in total students, 8.47 (8.36-8.58) in boys, and 8.33
      (8.18-8.48) in girls. In the 7-12 and 13-18 years' age groups, these values were
      8.47 (8.32-8.63) and 8.34 (8.22-8.45) in total, 8.39 (8.26-8.52) and 8.47 (8.33
      8.61) in boys, 8.33 (8.11-8.55) and 8.35 (8.22-8.47) in girls, respectively.
      CONCLUSION: The findings of this study can be clinically helpful for screening
      MetS in children and adolescents but the effectiveness of these criteria needs to
      be evaluated by further longitudinal surveys. LEVEL OF EVIDENCE: Level V, cross
      sectional descriptive study (National surveillance study).

PMID- 29453592
TI  - Patient-specific registration of 3D CT angiography (CTA) with X-ray fluoroscopy
      for image fusion during transcatheter aortic valve implantation (TAVI) increases
      performance of the procedure.
AB  - OBJECTIVES: The aim of this study was to adapt patient-specifically a co
      registration procedure for image fusion (IF) of a pre-interventional CT dataset
      with real-time X-ray (XR) fluoroscopy during transfemoral transcatheter aortic
      valve implantation (TAVI), enabling improved performance of the procedure.
      BACKGROUND: The ability to use 3D models of the respective anatomies to
      complement the anatomic information obtained by XR fluoroscopy and provide a
      greater degree of real-time anatomical guidance holds great potential for complex
      cardiac interventions, especially for TAVI procedures with cerebral protection.
      METHODS: Initial registration of two datasets was performed during the femoral
      puncture and sheath introduction using routinely acquired arteriographies. On
      time refinement of the co-registration was then performed during the on-going
      procedure avoiding additional angiograms for the co-registration. Performance of
      the method was evaluated quantitatively in terms of procedural characteristics
      and clinical events. RESULTS: Significant reduction of the radiation dose [51 (42
      55) vs. 64 (49-81) Gy cm2, p = 0.032] and contrast agent (CA) volume [80 (50-95)
      vs. 100 (80-110) ml, p = 0.010] was achieved with the optimized approach as
      compared to the control group without IF, with simultaneous decrease of
      procedural [48 (41-58) vs. 61 (53-67) min, p = 0.002] and fluoroscopy times [14.8
      (12.7-18.5) vs. 17.8 (14.3-19.4), p = 0.108]. CONCLUSIONS: In this proof-of
      concept study we have demonstrated a novel co-registration approach for IF during
      TAVI not requiring any additional CA or XR scan. We have evaluated its potential
      benefit with the strong focus on guiding the femoral puncture, placement of the
      double-filter cerebral embolic protection device, and deployment of the valve
      prosthesis. We achieved improved performance and safety of the procedure with the
      introduced approach.

PMID- 29453593
TI  - Risk marker profiles in patients treated with percutaneous septal ablation for
      symptomatic hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND AND STUDY OBJECTIVE: Different studies have shown a good long-term
      survival with improvement of symptoms and hemodynamics after percutaneous septal
      ablation (PTSMA), similar to myectomy considered to be the therapeutic "gold
      standard" for symptomatic hypertrophic obstructive cardiomyopathy (HOCM).
      Furthermore, desobliteration of left ventricular (LV) outflow may modify features
      of the disease considered to be risk-relevant, such as magnitude of LV
      hypertrophy, outflow gradient, and left atrial (LA) size. The aim oft this study
      was to examine predictors of long-term mortality in a large cohort of patients
      with HOCM treated with PTSMA. METHODS AND RESULTS: 497 consecutive patients with
      symptomatic HOCM (mean age 55.4 +/- 14.4 years, NYHA class: 2.9 +/- 0.4) who
      underwent PTSMA between 1996 and 2014 were studied. Periprocedural mortality was
      1% (five patients). During a follow-up time of 64.5 +/- 53.2 months (range 0.1
      207), 51 patients died, of these 25 due to cardiovascular problems, while 26
      deaths were attributed to non-cardiac causes. Overall survival rates were 89.4%
      (+/- 1.7) after 5 and 80.6% (+/- 2.7) after 10 years. Among the baseline
      variables, advanced age, recurrent syncope, and magnitude of LV thickening were
      risk markers correlated to long-term post-procedural survival. The only mortality
      predictor that could be identified during follow-up was post-procedural NYHA
      class. Neither the other classical HCM risk markers nor other clinical or
      echocardiographic parameters predicted cardiac or all-cause mortality in this
      cohort. CONCLUSIONS: Our findings suggest that the risk profile after septal
      ablation may differ from that of HOCM patients without an outflow
      desobliteration.

PMID- 29453594
TI  - Time-to-first-event versus recurrent-event analysis: points to consider for
      selecting a meaningful analysis strategy in clinical trials with composite
      endpoints.
AB  - BACKGROUND: Composite endpoints combining several event types of clinical
      interest often define the primary efficacy outcome in cardiologic trials. They
      are commonly evaluated as time-to-first-event, thereby following the
      recommendations of regulatory agencies. However, to assess the patient's full
      disease burden and to identify preventive factors or interventions, subsequent
      events following the first one should be considered as well. This is especially
      important in cohort studies and RCTs with a long follow-up leading to a higher
      number of observed events per patients. So far, there exist no recommendations
      which approach should be preferred. DESIGN: Recently, the Cardiovascular Round
      Table of the European Society of Cardiology indicated the need to investigate
      "how to interpret results if recurrent-event analysis results differ [...] from
      time-to-first-event analysis" (Anker et al., Eur J Heart Fail 18:482-489, 2016).
      This work addresses this topic by means of a systematic simulation study.
      METHODS: This paper compares two common analysis strategies for composite
      endpoints differing with respect to the incorporation of recurrent events for
      typical data scenarios motivated by a clinical trial. RESULTS: We show that the
      treatment effects estimated from a time-to-first-event analysis (Cox model) and a
      recurrent-event analysis (Andersen-Gill model) can systematically differ,
      particularly in cardiovascular trials. Moreover, we provide guidance on how to
      interpret these results and recommend points to consider for the choice of a
      meaningful analysis strategy. CONCLUSIONS: When planning trials with a composite
      endpoint, researchers, and regulatory agencies should be aware that the model
      choice affects the estimated treatment effect and its interpretation.

PMID- 29453595
TI  - Cardio-oncology: conflicting priorities of anticancer treatment and
      cardiovascular outcome.
AB  - BACKGROUND: This article about the emerging field of cardio-oncology highlights
      typical side effects of oncological therapies in the cardiovascular system,
      cardiovascular complications of malignancies itself, and potential preventive or
      therapeutic modalities. METHODS: We performed a selective literature search in
      PubMed until September 2016. RESULTS: Cardiovascular events in cancer patients
      can be frequently attributed to oncological therapies or to the underlying
      malignancy itself. Furthermore, many patients with cancer have pre-existing
      cardiovascular diseases that can be aggravated by the malignancy or its therapy.
      Cardiovascular abnormalities in oncological patients comprise a broad spectrum
      from alterations in electrophysiological, laboratory or imaging tests to the
      occurrence of thromboembolic, ischemic or rhythmological events and the
      impairment of left ventricular function or manifest heart failure. DISCUSSION: A
      close interdisciplinary collaboration between oncologists and
      cardiologists/angiologists as well as an increased awareness of potential
      cardiovascular complications could improve clinical care of cancer patients and
      provides a basis for an improved understanding of underlying mechanisms of
      cardiovascular morbidity.

PMID- 29453599
TI  - Sequential analysis in neonatal research-systematic review.
AB  - : As more new drugs are discovered, traditional designs come at their limits. Ten
      years after the adoption of the European Paediatric Regulation, we performed a
      systematic review on the US National Library of Medicine and Excerpta Medica
      database of sequential trials involving newborns. Out of 326 identified
      scientific reports, 21 trials were included. They enrolled 2832 patients, of whom
      2099 were analyzed: the median number of neonates included per trial was 48 (IQR
      22-87), median gestational age was 28.7 (IQR 27.9-30.9) weeks. Eighteen trials
      used sequential techniques to determine sample size, while 3 used continual
      reassessment methods for dose-finding. In 16 studies reporting sufficient data,
      the sequential design allowed to non-significantly reduce the number of enrolled
      neonates by a median of 24 (31%) patients (IQR - 4.75 to 136.5, p = 0.0674) with
      respect to a traditional trial. When the number of neonates finally included in
      the analysis was considered, the difference became significant: 35 (57%) patients
      (IQR 10 to 136.5, p = 0.0033). CONCLUSION: Sequential trial designs have not been
      frequently used in Neonatology. They might potentially be able to reduce the
      number of patients in drug trials, although this is not always the case. What is
      known: * In evaluating rare diseases in fragile populations, traditional designs
      come at their limits. About 20% of pediatric trials are discontinued, mainly
      because of recruitment problems. What is new: * Sequential trials involving
      newborns were infrequently used and only a few (n = 21) are available for
      analysis. * The sequential design allowed to non-significantly reduce the number
      of enrolled neonates by a median of 24 (31%) patients (IQR - 4.75 to 136.5, p =
      0.0674).

PMID- 29453600
TI  - Argininosuccinate Synthetase-1 (ASS1) Loss in High-Grade Neuroendocrine
      Carcinomas of the Urinary Bladder: Implications for Targeted Therapy with ADI-PEG
      20.
AB  - High-grade neuroendocrine carcinomas (HGNECs) of the urinary bladder encompass
      small cell (SCNEC) and large cell neuroendocrine carcinomas (LCNEC). Currently,
      recommended initial management is with systemic chemotherapy, followed by
      consolidative therapy with either radical cystectomy or radiotherapy in patients
      with localized disease. Nevertheless, survival in this setting remains poor. We
      therefore evaluated the potential to modify arginine metabolism as an
      alternative, targeted therapy approach in these carcinomas. In humans, arginine
      is a semi-essential amino acid and its synthesis enzyme argininosuccinate
      synthetase (ASS1) represents the rate-limiting step in arginine biosynthesis.
      Neoplasms that show low to absent ASS1 expression require extracellular arginine
      for cancer cell survival, and thus can be targeted using arginine-degrading
      enzymes such as pegylated arginine deiminase (ADI-PEG 20). An initial study by
      our group of 19 patients demonstrated that a high percentage of SCNEC lack ASS1
      expression. Herein, we evaluated an expanded cohort of 74 radical cystectomy
      patients with HGNEC, including 63 SCNEC, 5 LCNEC, and 6 mixed morphology HGNEC
      patients. ASS1 expression was assessed through immunohistochemistry. Fifty-eight
      (of 74, 78%) patients with HGNEC showed absent ASS1 expression, including all
      patients with LCNEC and mixed morphology (11 of 11, 100%). Ten-year survival from
      disease-specific death was not statistically significant between ASS1-expressing
      and ASS1-deficient cases (p = 0.75). Our results show that HGNEC of the bladder
      may be candidates for arginine deprivation therapy using drugs such as ADI-PEG
      20. Further studies are needed to validate these findings and to determine the
      therapeutic efficacy of such agents.

PMID- 29453596
TI  - Effectiveness of the sesquiterpene (-)-alpha-bisabolol in dogs with naturally
      acquired canine leishmaniosis: an exploratory clinical trial.
AB  - The use of natural products is a promising approach for treating visceral
      leishmaniosis. (-)-alpha-Bisabolol is a sesquiterpene that have been proved
      active in vivo on Leishmania infantum-infected mice without showing toxicity. A
      single-centre, parallel-group, randomized, exploratory study was designed to
      assess its efficacy in a canine leishmaniosis model involving naturally infected
      dogs. In this clinical trial, 12 dogs were allocated into two groups and were
      treated with either meglumine antimoniate (100 mg/kg) through subcutaneous route
      or (-)-alpha-bisabolol (30 mg/kg) through oral route for two treatment series of
      30 days, separated by a 30-day interval. A 4-month follow-up period was
      established as well. Parasite loads in bone marrow, lymph node and blood were
      estimated through quantitative PCR. Antibody titres were determined through
      immunofluorescence antibody test and cytokine expression values were estimated
      through real-time reverse transcription-PCR. Treatment safety was assessed
      through the evaluation of weight, gastrointestinal alterations and hematological
      and biochemical parameters in blood. Analyses were performed before and after
      treatment, and after a 4-months follow-up period. Treatment with the
      sesquiterpene was effective at decreasing parasite loads and increasing gamma
      interferon expression level. Dogs treated with (-)-alpha-bisabolol did not show
      any toxicity sign. These results were better than those obtained using the
      reference drug, meglumine antimoniate. The natural compound seemed to induce a
      Th1 immune response that led to parasitological and clinical improvement without
      showing any safety issue, suggesting a high potential for the treatment of canine
      and human visceral leishmaniosis.

PMID- 29453602
TI  - Tight software, methodological/physiological variation, less so.

PMID- 29453601
TI  - Immunohistochemical Biomarkers in Pituitary Pathology.
AB  - Pituitary pathology is one area of endocrine pathology that is highly dependent
      on immunohistochemistry. There is a wide range of disorders that occur in and
      around the sella turcica, and the distinction of tumor-like lesions from
      neoplasms requires careful evaluation. The diagnosis, prognosis, and predictive
      features of neoplasms in the sellar region are all dependent on the application
      and interpretation of biomarkers of cell differentiation, hormonal activity,
      subcellular morphology, and proliferation. As in hematopathology, the number of
      biomarkers has increased dramatically and continues to increase. Fortunately,
      some of the biomarkers provide information that was initially dependent on
      electron microscopy; therefore, the need for this additional technology has been
      reduced to only rare unusual tumors. In this review, we provide a simple approach
      to understanding the importance of the various biomarkers that are used to ensure
      the correct diagnosis and provide the treating clinicians with tools to guide
      appropriate patient management and surveillance.

PMID- 29453603
TI  - Repeatable and reproducible measurements of myocardial oxidative metabolism,
      blood flow and external efficiency using 11C-acetate PET.
AB  - BACKGROUND: Non-invasive approaches to investigate myocardial efficiency can help
      track the progression of heart failure (HF). This study evaluates the
      repeatability and reproducibility of 11C-acetate positron emission tomography
      (PET) imaging of oxidative metabolism. METHODS AND RESULTS: Dynamic 11C-acetate
      PET scans were performed at baseline and followup (47 +/- 22 days apart) in 20
      patients with stable HF with reduced ejection fraction. Two observers blinded to
      patients' clinical data used FlowQuant(r) to evaluate test-retest repeatability,
      as well as intra- and inter-observer reproducibility of 11C-acetate tracer uptake
      and clearance rates, for the measurement of myocardial oxygen consumption (MVO2),
      myocardial external efficiency (MEE), work metabolic index (WMI), and myocardial
      blood flow. Reproducibility and repeatability were evaluated using intra-class
      correlation (ICC) and Bland-Altman coefficient-of-repeatability (CR). Test-retest
      correlations and repeatability were better for MEE and WMI compared to MVO2. All
      intra- and inter-observer correlations were excellent (ICC = 0.95-0.99) and the
      reproducibility values (CR = 3%-6%) were significantly lower than the test-retest
      repeatability values (22%-54%, P < 0.001). Repeatability was improved for all
      parameters using a newer PET-computed tomography (CT) scanner compared to older
      PET-only instrumentation. CONCLUSION: 11C-acetate PET measurements of WMI and MEE
      exhibited excellent test-retest repeatability and operator reproducibility. Newer
      PET-CT scanners may be preferred for longitudinal tracking of cardiac efficiency.

PMID- 29453604
TI  - Evaluating the impact of spirituality on the quality of life, anxiety, and
      depression among patients with cancer: an observational transversal study.
AB  - OBJECTIVE: Spiritual well-being was found to have some protective effect against
      end-of life despair in cancer patients. We aimed at assessing the impact of
      spirituality on the quality of life, depression, and anxiety of Lebanese cancer
      patients. METHODS: Our observational transversal monocentric study was conducted
      between January and April 2016 among a convenient sample of 115 Lebanese cancer
      patients admitted to Hotel-Dieu de France Hospital (HDF), Beirut-Lebanon. In
      addition to socio-demographic and clinical data, three questionnaires were used:
      EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality
      of Life Questionnaire, 3rd version), FACIT-Sp-12 (Functional Assessment of
      Chronic Illness Therapy-Spiritual Well-Being; The 12-item Spiritual Well-Being
      Scale, 4th version), and HADS (Hospital Anxiety and Depression Scale). Eighteen
      patients taking anxiolytic and/or antidepressants were not included in the
      analysis. The remaining 97 patients were analyzed. RESULTS: Better emotional and
      cognitive functioning was seen in patients with higher meaning, peace, faith, and
      total FACIT scores. Meaning, peace, and total FACIT scores were also higher among
      patients with better global health status and quality of life. Anxiety as well as
      depression was significantly associated to all spiritual well-being factors.
      CONCLUSION: Spirituality can improve quality of life and decrease the incidence
      of anxiety and depression in cancer patients. Our results highlight the need to
      incorporate spiritual care in healthcare systems.

PMID- 29453605
TI  - Enhanced recovery after surgery-ERAS-principles, practice and feasibility in the
      elderly.
AB  - This is a short overview of the principles of a novel development in surgery
      called enhanced recovery after surgery (ERAS) programs. This is an evidence-based
      approach to perioperative care that has shown to reduce complications and
      recovery time by 30-50%. The main mechanism is reduction of the stress reactions
      to the operation. These principles have been shown to be particularly well suited
      for the compromised patient and hence very good for the elderly people who often
      have co-morbidities and run a higher risk of complications.

PMID- 29453606
TI  - Effect of topiroxostat in patients with diabetic nephropathy and gout or
      hyperuricemia: fact or fallacy.

PMID- 29453607
TI  - Semaphorin 7A in circulating regulatory T cells is increased in autosomal
      dominant polycystic kidney disease and decreases with tolvaptan treatment.
AB  - BACKGROUND: Semaphorin 7A (SEMA7A) is an immunomodulating protein implicated in
      lung and liver fibrosis. In autosomal-dominant polycystic kidney disease (ADPKD),
      the progressive expansion of renal cysts, inflammation, and subsequent renal
      fibrosis leads to end-stage renal disease (ESRD). SEMA7A may play a role in renal
      fibrosis and in ADPKD. METHODS: We evaluated Sema7a in a mouse model of renal
      fibrosis and determined the expression of SEMA7A in human ADPKD kidney. We
      analyzed SEMA7A expression on peripheral blood mononuclear cells (PBMCs),
      including CD45+ (leukocyte), CD14+(monocyte), CD4+ (T lymphocytes) and
      CD4+Foxp3+CD25+ [regulatory T lymphocytes (Tregs)] from 90 ADPKD patients (11
      tolvaptan treated and 79 tolvaptan naive), and 21 healthy volunteers, using a
      Fluorescence-Activated Cell Sorting (FACS). RESULTS: Sema7a is required for renal
      fibrosis. SEMA7A shows robust expression in ADPKD kidneys, localizing to cysts
      derived from distal tubules. SEMA7A is higher in circulating monocytes, but
      unchanged in CD4+ lymphocytes in ADPKD patients. The SEMA7A increase was detected
      early (stage 1 CKD) and seemed more prominent in patients with smaller kidneys (p
      = 0.09). Compared to tolvaptan-naive ADPKD patients, those treated with tolvaptan
      showed reduced SEMA7A expression on monocytes, T lymphocytes, and Tregs, although
      the number of PBMCs was unchanged. After 1 month of tolvaptan treatment, SEMA7A
      expression on Tregs decreased. CONCLUSIONS: SEMA7A shows potential as both a
      therapeutic target in mammalian kidney fibrosis and as a marker of inflammation
      in ADPKD patients. SEMA7A expression was lower after tolvaptan treatment, which
      may reflect drug efficacy.

PMID- 29453609
TI  - Leptin receptor gene (A/G) polymorphism rs1137101 and renal cell carcinoma.
AB  - Leptin plays an important role in carcinogenesis as leptin/leptin receptor
      signaling promotes the angiogenesis, proliferation, and inhibits epithelial cell
      apoptosis. Variants in the leptin receptor gene have potential associations with
      renal cell carcinoma (RCC). We aimed to investigate association of rs1137101
      (A/G) polymorphism at LEPR gene with risk of RCC and patients survival. 123
      individuals were classified into group I: 73 RCC patients and group II: 50
      healthy controls. Genotyping of the Gln223Arg (A/G) polymorphism rs1137101 at
      LEPR gene was analyzed using allelic discrimination assay by Real-Time PCR
      technique. GG genotype was the most frequent among RCC patients (67.1%), while AA
      genotype was the most frequent in controls (60%); (p < 0.001). By univariate cox
      regression: gene polymorphism (GG versus GA +AA), stage, histopathologic subtype,
      and grade were found to affect survival significantly; however, the multivariate
      analysis showed that only gene polymorphism (GG versus GA +AA) and tumor stage
      significantly affect survival. LEPR gene variants rs1137101 might be a candidate
      risk factor for RCC in Egypt. GG genotype is associated with more aggressive
      tumor behavior and shorter survival compared with GA & AA genotypes so,
      genotyping of Gln223Arg (A/G) rs1137101 could also predict RCC outcome.

PMID- 29453608
TI  - Chemopreventive action of Imatinib, a tyrosine kinase inhibitor in the regulation
      of angiogenesis and apoptosis in rat model of lung cancer.
AB  - The present study explored the events of angiogenesis and apoptosis in 7,12
      dimethyl benz(a)anthracene (DMBA)-induced lung cancer in rat and its
      chemoprevention with Imatinib, a receptor tyrosine kinase inhibitor. Further, it
      includes  lipopolysaccharide (LPS) mediating inflammation along with DMBA for the
      promotion of lung carcinogenesis. The animals received a single intratracheal
      instillation of DMBA (20 mg/kg body weight) in olive oil and LPS (0.6 mg/kg body
      weight) to induce tumors in 16 weeks. Besides morphology and histology of the
      lung tissues, RT-PCR, western blots, and immunofluorescence were performed for
      the expression of apoptotic and angiogenic proteins. Apoptosis was studied by
      mitochondrial Bcl-2/Bax ratio and staining with the dyes Acridine orange/ethidium
      bromide of the isolated Broncho epithelial cells. Also, mitochondrial membrane
      potential (DeltaPsiM) was studied by JC-1. The study revealed that the expression
      of VEGF, MMP-2, MMP-9, and the chemokine MCP-1 to be very high in DMBA and DMBA +
      LPS groups, while Bcl-2 also shows an elevated expression. These results were
      restored with Imatinib treatment. The pro-apoptotic proteins, Bax, Bad, Apaf-1,
      and Caspase-3 were highly diminished in DMBA and DMBA + LPS groups which were
      recovered with Imatinib treatment.

PMID- 29453611
TI  - Comparative study of phototoxicity of protoporphyrin IX synthetic and extracted
      from ssp Rattus novergicus albinus rats toward murine melanoma cells.
AB  - Protoporphyrin IX (PpIX) is a precursor of heme synthesis and is known to be an
      active photosensitizer and precursor of photosensitizers applied in photodynamic
      therapy (PDT) and photodynamic diagnostics (PDD). On irradiation with visible
      light, PpIX undergoes phototransformation, producing photoproducts which may also
      be phototoxic and increase its efficacy. The mechanism of PpIX
      phototransformation depends on environmental characteristics and can be different
      in vitro and in vivo. In this paper, we present a comparative study of the
      photoactivity of synthetic PpIX and PpIX extracted from the Harderian gland of
      ssp Rattus novergicus albinus rats, along with their photoproducts toward murine
      B16F-10 melanoma cells. It was observed that when irradiated with visible light
      the endogenous PpIX demonstrates photocytotoxicity ten times higher than the
      synthetic PpIX. The photoproduct of endogenous PpIX also possesses phototoxicity,
      though slightly lower than that of PpIX itself. The rate of cell internalization
      for both endogenous PpIX and its photoproduct was eightfold greater than that
      obtained for the synthetic porphyrin. This difference might result from a
      complexation of the native PpIX with some amphiphilic compounds during its
      synthesis within the Harderian glands, which facilitates the cell uptake of PpIX.
      Fluorescence microscopy images show that both endogenous and synthetic porphyrins
      are localized after uptake predominantly in the mitochondrial region of cells.

PMID- 29453610
TI  - Hepatitis C Cure Is Associated with Decreased Healthcare Costs in Cirrhotics in
      Retrospective Veterans Affairs Cohort.
AB  - BACKGROUND: Approximately 233,898 individuals in the Veterans Affairs healthcare
      network are hepatitis C virus (HCV)-infected, making the Veterans Affairs the
      single largest provider of HCV care in the USA. Direct-acting antiviral treatment
      regimens for HCV offer high cure rates. However, these medications pose an
      enormous financial burden, and whether HCV cure is associated with decreased
      healthcare costs is poorly defined. AIMS: To measure downstream healthcare costs
      in a national population of HCV-infected patients up to 9 years post-HCV
      antiviral treatment, to compare downstream healthcare costs between cured and
      uncured patients, and to assess impact of cirrhosis status on cost differences.
      METHODS: This is a retrospective cohort study (2004-2014) of hepatitis C-infected
      patients who initiated antiviral treatment within the United States Veterans
      Affairs healthcare system October 2004-September 2013. We measured inpatient,
      outpatient, and pharmacy costs after HCV treatment. RESULTS: For the entire
      cohort, cure was associated with mean cumulative cost savings in post-treatment
      years three-six, but no cost savings by post-treatment year nine. By post
      treatment year nine, cure in cirrhosis patients was associated with a mean
      cumulative cost savings of $9474 (- 32,666 to 51,614) per patient, while cure in
      non-cirrhotic patients was associated with a mean cumulative cost excess of $2526
      (- 12,211 to 7159) per patient. CONCLUSIONS: Among patients with cirrhosis at
      baseline, cure is associated with absolute cost savings up to 9 years post
      treatment compared to those without cure. Among patients without cirrhosis, early
      post-treatment cost savings are counterbalanced by higher costs in later years.

PMID- 29453612
TI  - Ancylomarina psychrotolerans sp. nov., isolated from sediments of Fildes
      Peninsula and emended the description of genus Ancylomarina.
AB  - A Gram-stain negative, obligately anaerobic, non-motile, asporogenous long rod
      shaped and non-flagellated bacterial strain, designated 4SWWS2-6T, was isolated
      from sediment in the intertidal zone of Fildes Peninsula, Antarctica.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain
      4SWWS2-6T belongs to the genus Ancylomarina and showed high sequence similarity
      with Ancylomarina subtilis FA102T (96.5%). Optimal growth occurred at pH 6.5, 16 
      degrees C and in the presence of 3% (w/v) NaCl. Strain 4SWWS2-6T contained
      menaquinone-7 (MK-7) as the major respiratory quinone and held iso-C15:0, anteiso
      C15:0 and iso-C15:0 3-OH as the major cellular fatty acids. The major polar
      lipids were phosphatidylethanolamine, phosphatidylmonomethylethanolamine, an
      aminolipid, two unidentified lipids and an unidentified phospholipid. The DNA G +
      C content of strain 4SWWS2-6T was 37.6 mol%. On the basis of the polyphasic
      analyses, strain 4SWWS2-6T is considered to represent a novel species in the
      genus Ancylomarina, for which the name Ancylomarina psychrotolerans sp. nov. is
      proposed. The type strain is 4SWWS2-6T (= KCTC 15504T = MCCC 1K01618T).

PMID- 29453613
TI  - In Vitro Antioxidant and Cytotoxic Activities of 18 Plants from the Erkowit
      Region, Eastern Sudan.
AB  - We investigated the antioxidant potential and cytotoxicity towards human CCRF-CEM
      leukemia cells of 57 extracts obtained from 18 plants collected in the Erkowit
      region, eastern Sudan. The antioxidant activity was determined by measuring the
      radical scavenging effects against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and N,N
      dimethyl-p-phenylendiamine (DMPD), metal-chelation capacity, ferric-reducing
      (FRAP) and phosphomolibdenum-reducing antioxidant power (PRAP) methods using
      ELISA microtiter assays. Total phenol and flavonoid amounts of the extracts were
      determined spectrophotometrically. Cytotoxicity towards CCRF-CEM cells was
      evaluated by the resazurin reduction assay. Geranium favosum followed by
      Kalanchoe glaucescens, Malva parviflora, Aizoon canariense, and Coleus barbatus,
      respectively, possessed the highest antioxidant activity among the studied
      plants. Chrozophora oblongifolia and K. glaucescens exerted considerable
      cytotoxicity against CCRF-CEM leukemia cells. These plants may serve as source
      for the further development of natural antioxidant and antitumor agents.

PMID- 29453614
TI  - Screening of Isochrysis Strains and Utilization of a Two-Stage Outdoor
      Cultivation Strategy for Algal Biomass and Lipid Production.
AB  - Isochrysis is a genus of marine algae without cell wall and capable of
      accumulating lipids. In this study, the lipid production potential of Isochrysis
      was assessed by comparing 15 Isochrysis strains with respect to their growth
      rate, lipid production, and fatty acid profiles. Three best strains were selected
      (lipid productivity, 103.0~121.7 mg L-1 day-1) and their lipid-producing
      capacities were further examined under different controlled parameters, e.g.,
      growth phase, medium nutrient, and light intensity in laboratory cultures.
      Furthermore, the three Isochrysis strains were monitored in outdoor panel
      photobioreactors with various initial cell densities and optical paths, and the
      strain CS177 demonstrated the superior potential for outdoor cultivation. A two
      stage semi-continuous strategy for CS177 was subsequently developed, where high
      productivities of biomass (1.1 g L-1 day-1) and lipid (0.35 g L-1 day-1) were
      achieved. This is a comprehensive study to evaluate the lipid-producing
      capability of Isochrysis strains under both indoor and outdoor conditions.
      Results of the present work lay a solid foundation for the physiological and
      biochemical responses of Isochrysis to various conditions, shedding light on the
      future utilization of this cell wall-lacking marine alga for biofuel production.

PMID- 29453615
TI  - Vidarabine, an anti-herpesvirus agent, prevents catecholamine-induced arrhythmias
      without adverse effect on heart function in mice.
AB  - Sympathetic activation causes clinically important arrhythmias including atrial
      fibrillation (AF) and ventricular tachyarrhythmia. Although the usefulness of
      beta-adrenergic receptor blockade therapy is widely accepted, its multiple
      critical side effects often prevent its initiation or continuation. The aim of
      this study is to determine the advantages of vidarabine, an adenylyl cyclase (AC)
      targeted anti-sympathetic agent, as an alternative treatment for arrhythmia. We
      found that vidarabine, which we identified as a cardiac AC inhibitor,
      consistently shortens AF duration and reduces the incidence of sympathetic
      activation-induced ventricular arrhythmias. In atrial and ventricular myocytes,
      vidarabine inhibits adrenergic receptor stimulation-induced RyR2 phosphorylation,
      sarcoplasmic reticulum (SR) Ca2+ leakage, and spontaneous Ca2+ release from SR,
      the last of which has been considered as a potential arrhythmogenic trigger.
      Moreover, vidarabine also inhibits sympathetic activation-induced reactive oxygen
      species (ROS) production in cardiac myocytes. The pivotal role of vidarabine's
      inhibitory effect on ROS production with regard to its anti-arrhythmic property
      has also been implied in animal studies. In addition, as expected, vidarabine
      exerts an inhibitory effect on AC function, which is more potent in the heart
      than elsewhere. Indexes of cardiac function including ejection fraction and heart
      rate were not affected by a dosage of vidarabine sufficient to exert an anti
      arrhythmic effect. These findings suggest that vidarabine inhibits catecholamine
      induced AF or ventricular arrhythmia without deteriorating cardiac function in
      mice.

PMID- 29453617
TI  - Site suitability evaluation of an old operating landfill using AHP and GIS
      techniques and integrated hydrogeological and geophysical surveys.
AB  - Because of the outdated methods of common landfill selection, it is imperative to
      reevaluate the usage suitability. To assess the suitability of the existing waste
      landfill in Zanjan, Iran, we have used a combination of the analytical hierarchy
      process (AHP) and GIS techniques, along with fieldwork surveys. Four major
      criteria and 12 subcriteria were considered, and the AHP was applied to assign
      the relative importance weights of criteria and subcriteria to each other.
      Finally, a landfill suitability map was generated and ranked based on the final
      suitability scores. The results show that the unsuitable areas are around Zanjan,
      in the middle parts of the plain. By contrast, the most suitable areas are
      uncultivated areas, located mostly in the west, north, and south. The results
      also indicate that the present landfill is a highly suitable site. After desk
      studies, geoelectrical surveys and infiltration measurements were conducted to
      make the final decision. Double-ring permeability tests confirm the landfill is
      an acceptable site. The electrical sounding shows that the leachate plume has a
      width of about ~ 450 m, spreads to a depth of about ~ 55 m, and migrates towards
      the northeast. Considering the groundwater depth, dry climate, and a low
      infiltration rate of the landfill soils, it can be concluded that leachate plumes
      will not contaminate groundwater within this decade. The proposed method can be
      implemented to reevaluate the suitability of any old operating reservoir such as
      oil reservoirs, petrol filling stations, heavy industrial tanks, and landfills,
      containing liquid hazardous materials.

PMID- 29453616
TI  - Laser-induced plasma spectroscopy (LIPS): use of a geological tool in assessing
      bone mineral content.
AB  - Bone may be similar to geological formulations in many ways. Therefore, it may be
      logical to apply laser-based geological techniques in bone research. The mineral
      and element oxide composition of bioapatite can be estimated by mathematical
      models. Laser-induced plasma spectrometry (LIPS) has long been used in geology.
      This method may provide a possibility to determine the composition and
      concentration of element oxides forming the inorganic part of bones. In this
      study, we wished to standardize the LIPS technique and use mathematical
      calculations and models in order to determine CaO distribution and bone
      homogeneity using bovine shin bone samples. We used polished slices of five
      bovine shin bones. A portable LIPS instrument using high-power Nd++YAG laser
      pulses has been developed (OpLab, Budapest). Analysis of CaO distribution was
      carried out in a 10 * 10 sampling matrix applying 300-MUm sampling intervals. We
      assessed both cortical and trabecular bone areas. Regions of interest (ROI) were
      determined under microscope. CaO peaks were identified in the 200-500 nm
      wavelength range. A mathematical formula was used to calculate the element oxide
      composition (wt%) of inorganic bone. We also applied two accepted mathematical
      approaches, the Bartlett's test and frequency distribution curve-based analysis,
      to determine the homogeneity of CaO distribution in bones. We were able to
      standardize the LIPS technique for bone research. CaO concentrations in the
      cortical and trabecular regions of B1-5 bones were 33.11 +/- 3.99% (range 24.02
      40.43%) and 27.60 +/- 7.44% (range 3.58-39.51%), respectively. CaO concentrations
      highly corresponded to those routinely determined by ICP-OES. We were able to
      graphically demonstrate CaO distribution in both 2D and 3D. We also determined
      possible interrelations between laser-induced craters and bone structure units,
      which may reflect the bone structure and may influence the heterogeneity of CaO
      distributions. By using two different statistical methods, we could confirm if
      bone samples were homogeneous or not with respect to CaO concentration
      distribution. LIPS, a technique previously used in geology, may be included in
      bone research. Assessment of element oxide concentrations in the inorganic part
      of bone, as well as mathematical calculations may be useful to determine the
      content of CaO and other element oxides in bone, further analyze bone structure
      and homogeneity and possibly apply this research to normal, as well as diseased
      bones.

PMID- 29453618
TI  - Lumbosacral transitional vertebrae: significance of local bone marrow edema at
      the transverse processes.
AB  - OBJECTIVE: To evaluate the association between low back pain and bone marrow
      edema in lumbosacral transitional vertebra (LSTV) transverse processes, and to
      assess the prevalence of LSTV in a physically active population. MATERIALS AND
      METHODS: Individuals with LSTV on coronal MRI studies were identified in a
      retrospective review by keyword search from PACS. In total, 140 cases were
      reviewed by two fellowship-trained musculoskeletal radiologists. Data on
      associated low back pain were collected from patient records at the time of the
      imaging. RESULTS: Bone marrow edema was observed in 44% of the cases, but no
      correlation with low back pain was found. On coronal MRI, the prevalence of LSTV
      was 2.6%, with type II LSTV being the most common subtype. CONCLUSIONS: No
      correlation with bone marrow edema at the transverse processes of the LSTV and
      low back pain was observed. In our selected study population, the prevalence of
      LSTV was low.

PMID- 29453619
TI  - An Electronic Medical Record Alert Intervention to Improve HPV Vaccination Among
      Eligible Male College Students at a University Student Health Center.
AB  - This pilot study aims to improve HPV vaccination for college aged males at a
      student health center. The first part of the study consisted of a focus group
      that assessed the barriers and facilitators of HPV vaccination among healthcare
      providers and clinic staff (N = 16). Providers reported missed opportunities for
      HPV vaccination. For the second part of the study, providers and staff reviewed
      medical records of patients ages 18-26 with student health insurance and with < 3
      doses of the HPV vaccine at baseline (12/1/2014 to 7/31/2015) and follow-up
      (12/1/2015 to 7/31/2016). A computer-automated EMR alert was generated in the
      medical record of eligible male patients (N = 386). Z-scores were estimated for
      two-sample proportions to measure change in HPV vaccine rates at baseline and
      follow-up for males and females. HPV vaccine initiation rates increased among
      males (baseline: 5.2% follow-up: 25.1%, p < 0.001). This study shows that EMR
      alerts improved HPV vaccine initiation rates among insured college-aged males.

PMID- 29453621
TI  - Response preparation, response selection difficulty, and response-outcome
      learning.
AB  - Voluntary action control is accomplished through anticipating that action's
      perceptual outcomes. Some evidence suggests that this is only true when responses
      are intention-based rather than stimulus-based and that this difference is
      evidence of different response modes. More recently, however, it has been shown
      that response-outcome retrieval effects can occur with stimulus-based responses,
      and that the retrieval depended on response selection efficiency as decreasing
      the response selection efficiency increased response-outcome retrieval (Gozli et
      al., J Exp Psychol: Hum Percept Perform, 2016). We look to extend this finding by
      manipulating response selection difficulty within (Experiment 1) or between
      blocks (Experiment 2) and response preparation time (Experiment 1) within an
      experiment. Individuals completed a task in which they responded to onsets using
      the spatially corresponding finger. The onset was preceded by precues narrowing
      down the response possibilities from four to two. The response possibilities were
      either on the same hand or different hands, such that response selection was easy
      or hard. We also varied the amount of time between the cues and the targets to
      manipulate response preparation time. The results indicated that trial-by-trial
      manipulations of response selection difficulty did not influence response-outcome
      retrieval, but that the between groups manipulation of response preparation time
      did. With less time response preparation time, larger response-outcome
      compatibility effects were found. This study presents further evidence that
      response selection efficiency can influence response-outcome retrieval and that
      this difference can be accounted for in terms of how prepared the responses are
      at the time of target presentation.

PMID- 29453620
TI  - Long-term hearing results of stapedotomy: analysis of factors affecting outcome.
AB  - OBJECTIVE: To evaluate long-term hearing results of stapedotomy and analyze the
      influence of patient-, disease-, and procedure-related variables. STUDY DESIGN:
      Retrospective case series. SETTING: Tertiary referral center. PATIENTS: 230 ears
      (202 patients, 10-74 years) underwent stapedotomy for otosclerosis between
      January 2008 and August 2014. All cases had early postoperative follow-up (4
      weeks post-surgery) and 181 cases had late postoperative follow-up (>= 1 year,
      average 32.5 months). INTERVENTION: Stapedotomy procedure for otosclerosis. MAIN
      OUTCOME MEASURES: Hearing outcome using conventional audiometry. The primary
      outcome parameter was the postoperative air-bone gap pure-tone average.
      Postoperative air-bone gap <= 10 dB was defined as surgical success.
      Preoperative, early postoperative and late postoperative hearing results were
      compared. Influence of patient- and procedure-related variables on hearing
      outcome was evaluated by logistic regression analysis. RESULTS: The postoperative
      air-bone gap was 10 dB or less in 77.0% of cases early post-surgery and in 70.7%
      of cases in long-term follow-up. Air-bone gap closure within 20 dB was obtained
      in 95.7 and 92.3%, respectively. Logistic regression analysis demonstrated that a
      larger preoperative air-bone gap (p = 0.041) and positive family history of
      otosclerosis (p = 0.044) were predictive for less surgical success early
      postoperatively, but not on the long term. Age, gender, primary versus revision
      surgery, presence of preoperative tinnitus and preoperative vertigo did not
      independently and significantly influence postoperative air-bone gap closure.
      CONCLUSION: Our series confirms excellent hearing results achieved in stapedotomy
      surgery, also in long-term follow-up. On the long-term no patient-, disease-, or
      procedure-related variables were identified as predictors of surgical success.

PMID- 29453622
TI  - Cognitive Mediators of Change in Physical Functioning in Response to a
      Multifaceted Intervention for Managing Osteoarthritis.
AB  - PURPOSE: Although non-pharmacological interventions have been shown to improve
      physical functioning in individuals with osteoarthritis (OA), the mechanisms by
      which this occurs are often unclear. This study assessed whether changes in
      arthritis self-efficacy, perceived pain control, and pain catastrophizing
      mediated changes in physical functioning following an osteoarthritis intervention
      involving weight management, physical activity, and cognitive-behavioral pain
      management. METHOD: Three hundred Veteran patients of 30 primary care providers
      with knee and/or hip OA were cluster randomized to an OA intervention group or
      usual care. The OA intervention included a 12-month phone-based patient
      behavioral protocol (weight management, physical activity, and cognitive
      behavioral pain management) plus patient-specific OA treatment recommendations
      delivered to primary care providers. RESULTS: Using linear mixed models adjusted
      for provider clustering, we observed that baseline to 6-month changes in
      arthritis self-efficacy and pain control partially mediated baseline to 12-month
      physical functioning improvements for the intervention group; catastrophizing did
      not. CONCLUSION: Findings of a mediating role of arthritis self-efficacy and pain
      control in intervention-related functional changes are consistent with hypotheses
      and align with theoretical assertions of the role of cognitions in cognitive and
      behavioral interventions for chronic pain. However, contrary to hypotheses,
      catastrophizing was not found to be a mediator of these changes.

PMID- 29453623
TI  - A novel suction/coagulation integrated probe for achieving better hemostasis:
      development and clinical use.
AB  - PURPOSES: Modern electrosurgical tools have a specific coagulation mode called
      "soft coagulation". However, soft coagulation has not been widely accepted for
      surgical operations. To optimize the soft coagulation environment, we developed a
      novel suction device integrated with an electrosurgical probe, called the
      "Suction ball coagulator" (SBC). In this study, we aimed to optimize the SBC
      design with a prototyping process involving a bench test and preclinical study;
      then, we aimed to demonstrate the feasibility, safety, and potential
      effectiveness of the SBC for laparoscopic surgery in clinical settings. METHODS:
      SBC prototyping was performed with a bench test. Device optimization was
      performed in a preclinical study with a domestic swine bleeding model. Then, SBC
      was tested in a clinical setting during 17 clinical laparoscopic colorectal
      surgeries. RESULTS: In the bench tests, two tip hole sizes and patterns showed a
      good suction capacity. The preclinical study indicated the best tip shape for
      accuracy. In clinical use, no device-related adverse event was observed.
      Moreover, the SBC was feasible for prompt hemostasis and blunt dissections. In
      addition, SBC could evacuate vapors generated by tissue ablation using
      electroprobe during laparoscopic surgery. CONCLUSIONS: We successfully developed
      a novel, integrated suction/coagulation probe for hemostasis and commercialized
      it.

PMID- 29453624
TI  - Hydroxyurea responses in clinically varied beta, HbE-beta thalassaemia and sickle
      cell anaemia patients of Eastern India.
AB  - The haematological and clinical response to hydroxyurea was estimated in HbE
      beta, beta thalassaemia and sickle cell anaemia patients of Eastern India, with
      variable clinical severity and transfusion requirement to determine whether
      hydroxyurea can help these patients to maintain their steady haemoglobin level
      without blood transfusions. Three hundred patients (189 HbE-beta thalassaemia, 95
      beta thalassaemia and 16 other haemoglobinopathies including sickle cell anaemia)
      were selected for hydroxyurea therapy and were followed up for 48-60 months.
      Results suggest significant response to hydroxyurea therapy in 19 beta and 99 HbE
      beta patients in the transfusion-dependent group (GR-I). All of them became
      transfusion-independent while on hydroxyurea therapy. The majority of responding
      patients were IVS1-5(G-C) in one of their alleles in HbE-beta cases (83 out of
      119). Though IVS1-5(G-C) was found to be the commonest mutation in our selected
      patients, the mutational background of the patients does not found to have any
      significant correlation with the response category towards hydroxyurea as per the
      results observed in our study. But, the drug works pretty well in most of the
      transfusion-dependent patients, as these patients were withdrawn from regular
      blood transfusion. At the same time, partial or no response to the drug
      hydroxyurea was also recorded in our study.

PMID- 29453625
TI  - Effects of feedstock and co-culture of Lactobacillus fermentum and wild
      Saccharomyces cerevisiae strain during fuel ethanol fermentation by the
      industrial yeast strain PE-2.
AB  - Even though contamination by bacteria and wild yeasts are frequently observed
      during fuel ethanol fermentation, our knowledge regarding the effects of both
      contaminants together is very limited, especially considering that the must
      composition can vary from exclusively sugarcane juice to a mixture of molasses
      and juice, affecting the microbial development. Here we studied the effects of
      the feedstock (sugarcane juice and molasses) and the co-culture of Lactobacillus
      fermentum and a wild Saccharomyces cerevisiae strain (rough colony and
      pseudohyphae) in single and multiple-batch fermentation trials with an industrial
      strain of S. cerevisiae (PE-2) as starter yeast. The results indicate that in
      multiple-cycle batch system, the feedstock had a minor impact on the fermentation
      than in single-cycle batch system, however the rough yeast contamination was more
      harmful than the bacterial contamination in multiple-cycle batch fermentation.
      The inoculation of both contaminants did not potentiate the detrimental effect in
      any substrate. The residual sugar concentration in the fermented broth had a
      higher concentration of fructose than glucose for all fermentations, but in the
      presence of the rough yeast, the discrepancy between fructose and glucose
      concentrations were markedly higher, especially in molasses. The biggest problem
      associated with incomplete fermentation seemed to be the lower consumption rate
      of sugar and the reduced fructose preference of the rough yeast rather than the
      lower invertase activity. Lower ethanol production, acetate production and higher
      residual sugar concentration are characteristics strongly associated with the
      rough yeast strain and they were not potentiated with the inoculation of L.
      fermentum.

PMID- 29453626
TI  - Drug approval based on randomized phase 3 trials for relapsed malignancy:
      analysis of oncologic drugs granted accelerated approval, publications and
      clinical trial databases.
AB  - Background As relapsed disease is frequently the first target of newly developed
      therapies, it is vital to address the difficulty in demonstrating the efficacy of
      new drugs for relapsed malignancy in randomized phase 3 trials. Methods We
      analyzed the approved indications, target populations, and development status of
      post-marketing confirmatory trials of all oncology-related drugs that were
      granted accelerated approval for both hematological and solid malignancies.
      Furthermore, we searched for randomized phase 3 trials for adult patients with
      relapsed lymphoid malignancy, other than chronic lymphocytic leukemia (CLL) and
      multiple myeloma (MM). Results Thirty-one (81.6%) of the 38 hematological
      indications and 23 (53.5%) of the 43 solid malignancy indications were in the
      relapsed settings. The target population of post-marketing studies was different
      from the approved indication in 18 (47.4%) of 38 hematological indications and 11
      (25.6%) of 43 solid malignancy indications; all 18 hematological indications
      involved relapsed settings. Improved time-to-event outcome for relapsed patients
      was the primary endpoint in 6 (19.3%) of the 31 relapsed hematological
      indications. In 4 published studies of relapsed lymphoid malignancy, the
      medication significantly improved outcomes. From 33 trials listed at
      Clinicaltrials.gov , 2 were positive and 13 were negative. Five out of the 13
      negative trials were terminated due to poor accrual. Conclusion Our analysis
      indicates that drug approval based on phase 3 trials is more challenging for
      relapsed hematological malignancies than for solid malignancies. Therefore,
      determining proper evaluation methods for the efficacy and safety of drugs for
      relapsed malignancy, without randomized trials, is important.

PMID- 29453627
TI  - A phase I and pharmacokinetic study of taladegib, a Smoothened inhibitor, in
      Japanese patients with advanced solid tumors.
AB  - Background This phase I dose-escalation study investigated the safety of the
      Smoothened inhibitor taladegib in Japanese patients with advanced solid tumors.
      Methods Patients received taladegib orally once daily for 28-day cycles, using a
      3 + 3 dose-escalation method. The primary objective was the safety and
      tolerability of taladegib at doses up to the global recommended dose (400 mg).
      Secondary objectives included pharmacokinetics, changes in skin glioma-associated
      oncogene homolog 1 (Gli1) transcript levels, and antitumor activity. Results
      Nineteen patients received treatment (100 mg: 3; 200 mg: 3; 400 mg: 13). No dose
      limiting toxicities (DLTs) were observed at doses of 100 mg or 200 mg; 3 of the 9
      patients evaluable for DLTs at the 400 mg dose level experienced DLTs
      (thrombocytopenia: 1; decreased appetite: 2). The most commonly reported
      treatment-related adverse events were dysgeusia (13/19, 68.4%), decreased
      appetite (12/19, 63.2%), nausea (9/19, 47.4%), fatigue (9/19, 47.4%), and
      vomiting (6/19, 31.6%). The pharmacokinetic profile suggested that exposure to
      taladegib was higher in Japanese than non-Japanese patients, possibly related to
      differences in body weight and/or drug formulation. At all dose levels, a high
      level of inhibition of skin Gli1 transcript levels was observed after 15 and 30
      days of exposure to taladegib. Partial response was achieved by 1 patient (basal
      cell carcinoma of the skin) and stable disease by 4 patients. Conclusions
      Taladegib doses of 100 mg and 200 mg, but not the global recommended dose of 400
      mg, were well tolerated in this population of Japanese patients with advanced
      solid tumors.

PMID- 29453628
TI  - Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted
      antibody-drug conjugate, in patients with relapsed or refractory B-cell non
      Hodgkin lymphoma: a dose-escalation, phase I study.
AB  - Background CD37 is expressed on B-cell lymphoid malignancies, thus making it an
      attractive candidate for targeted therapy in non-Hodgkin lymphoma (NHL). IMGN529
      is an antibody-drug conjugate comprising a CD37-binding antibody linked to the
      maytansinoid DM1, a potent anti-mitotic agent. Methods This first-in-human, phase
      1 trial recruited adult patients with relapsed or refractory B-cell NHL. The
      primary objective was to determine the maximum tolerated dose (MTD) and
      recommended phase 2 dose. Secondary objectives were to evaluate safety,
      pharmacokinetics, and preliminary clinical activity. IMGN529 was administered
      intravenously once every 3 weeks, and dosed using a conventional 3 + 3 dose
      escalation design. Results Forty-nine patients were treated at doses escalating
      from 0.1 to 1.8 mg/kg. Dose limiting toxicities occurred in eight patients and
      included peripheral neuropathy, febrile neutropenia, neutropenia, and
      thrombocytopenia. The most frequent treatment-emergent adverse events were
      fatigue (39%), neutropenia, pyrexia, and thrombocytopenia (each 37%). Adverse
      events led to treatment discontinuation in 10 patients (20%). Eight patients
      (16%) had treatment-related serious adverse events, the most common being grade 3
      febrile neutropenia. The MTD (with growth factor support) was 1.4 mg/kg every 3
      weeks. IMGN529 plasma exposure increased monotonically with dose and was
      consistent with target-mediated drug disposition. Five (13%) of 39 response
      evaluable patients achieved an objective response (one complete response and four
      partial responses), four of which occurred in the subgroup of patients with
      diffuse large B-cell lymphoma. Conclusions The manageable safety profile of
      IMGN529 and preliminary evidence of activity, particularly in DLBCL patients,
      support the continued development of this novel CD37-targeting agent.

PMID- 29453629
TI  - [The application of different injection methods for cervical and lumbar
      syndromes].
AB  - The differentiated consideration of cervical and lumbar pain syndromes leads to a
      decoding of complaints to assignable pain generators which enables a targeted
      injection method. Depending on the origin of pain injections are placed at the
      nerve root or the joints. Thus, the vicious cycle can be stopped. A correct
      technical procedure is of enormous importance. Because pharmacological effects
      and special complications are possible, monitoring and precautions are mandatory.

PMID- 29453630
TI  - Somatic BRCA1 mutations in clinically sporadic breast cancer with medullary
      histological features.
AB  - BACKGROUND: The role of somatic BRCA1/2 gene mutations in breast cancer is
      getting increasing attention in view of hereditary disease. The medullary
      phenotype and triple negative intrinsic subtypes are often, but not exclusively
      encountered in BRCA1 germline mutated breast cancer, whilst for BRCA2, no
      association to specific histological features are known. In this study, we
      addressed the relationship between morphological medullary phenotype and BRCA1/2
      somatic mutations in breast cancer without known positive family anamnesis.
      METHODS: 32 clinically sporadic breast cancers with medullary features were
      analyzed for somatic BRCA1/2 mutations (all coding exons) with next-generation
      sequencing technology. Paraffin-embedded formalin-fixed breast cancer samples
      from all patients were analyzed. RESULTS: Three of 32 tumors (9%) had pathogenic
      (ARUP class-5) BRCA1 gene alterations. Two of these pathogenic variants exhibited
      deletions leading to frameshift mutations (p.Glu23fs, p.Val1234fs), and the
      remaining single-nucleotid-variant resulted in premature STOP codon (p.Glu60Ter).
      In one patient, the same pathogenic BRCA1 mutation was detected (p.Glu23fs) in
      normal breast tissue. Retrospective follow-up in two patients revealed a positive
      family history for breast cancer and consecutive germline mutation testing
      confirmed presence of BRCA1 mutations. No somatic pathogenic BRCA2 mutations were
      detected. CONCLUSIONS: BRCA1 mutation testing may be useful in clinically
      sporadic breast cancer patients with medullary features to identify potential
      mutation carriers independently from intrinsic molecular subtype. Formalin-fixed
      paraffin-embedded cancer tissue can undergo testing within a routine molecular
      diagnostic setting as a clinical BRCA1/2 mutation screening strategy.

PMID- 29453631
TI  - Occupational Animal Allergy.
AB  - PURPOSE OF REVIEW: This review explores animal allergen exposure in research
      laboratories and other work settings, focusing on causes and prevention. RECENT
      FINDINGS: (1) Consistent with the hygiene hypothesis, there is new evidence that
      early childhood exposure to pets produces changes in the gut microbiome that
      likely lead to a lower risk of allergy. (2) Anaphylaxis from laboratory animal
      bites occurs more frequently than suggested by prior literature. (3) Animal
      allergens represent an occupational hazard in a wide variety of work settings
      ranging from fields that work with animals to public settings like schools and
      public transportation where allergens are brought into or are present in the
      workplace. Exposure to animal allergens can result in allergy, asthma, and
      anaphylaxis. Animal allergy has been most studied in the research laboratory
      setting, where exposure reduction can prevent the development of allergy. Similar
      prevention approaches need to be considered for other animal work environments
      and in all settings where animal allergens are present.

PMID- 29453632
TI  - Microbiota in fermented feed and swine gut.
AB  - Development of alternatives to antibiotic growth promoters (AGP) used in swine
      production requires a better understanding of their impacts on the gut
      microbiota. Supplementing fermented feed (FF) in swine diets as a novel
      nutritional strategy to reduce the use of AGP and feed price, can positively
      affect the porcine gut microbiota, thereby improving pig productivities. Previous
      studies have noted the potential effects of FF on the shift in benefit of the
      swine microbiota in different regions of the gastrointestinal tract (GIT). The
      positive influences of FF on swine gut microbiota may be due to the beneficial
      effects of both pre- and probiotics. Necessarily, some methods should be adopted
      to properly ferment and evaluate the feed and avoid undesired problems. In this
      mini-review, we mainly discuss the microbiota in both fermented feed and swine
      gut and how FF influences swine gut microbiota.

PMID- 29453633
TI  - Comparative analysis of the mitochondrial genome of the fungus Colletotrichum
      lindemuthianum, the causal agent of anthracnose in common beans.
AB  - Fungi of the genus Colletotrichum are economically important and are used as
      models in plant-pathogen interaction studies. In this study, the complete
      mitochondrial genomes of two Colletotrichum lindemuthianum isolates were
      sequenced and compared with the mitochondrial genomes of seven species of
      Colletotrichum. The mitochondrial genome of C. lindemuthianum is a typical
      circular molecule 37,446 bp (isolate 89 A2 2-3) and 37,440 bp (isolate 83.501) in
      length. The difference of six nucleotides between the two genomes is the result
      of a deletion in the ribosomal protein S3 (rps3) gene in the 83.501 isolate. In
      addition, substitution of adenine for guanine within the rps3 gene in the
      mitochondrial genome of the 83.501 isolate was observed. Compared to the
      previously sequenced C. lindemuthianum mitochondrial genome, an exon no annotated
      in the cytochrome c oxidase I (cox1) gene and a non-conserved open reading frame
      (ncORF) were observed. The size of the mitochondrial genomes of the seven species
      of Colletotrichum was highly variable, being attributed mainly to the ncORF,
      ranging from one to 10 and also from introns ranging from one to 11 and which
      encode a total of up to nine homing endonucleases. This paper reports for the
      first time by means of transcriptome that then ncORFs are transcribed in
      Colletotrichum spp. Phylogeny data revealed that core mitochondrial genes could
      be used as an alternative in phylogenetic relationship studies in Colletotrichum
      spp. This work contributes to the genetic and biological knowledge of
      Colletotrichum spp., which is of great economic and scientific importance.

PMID- 29453634
TI  - Comparison of serological and molecular typing methods for epidemiological
      investigation of Tenacibaculum species pathogenic for fish.
AB  - In the present study, the potential of serological methods, the repetitive
      extragenic palindromic PCR (REP-PCR) and the enterobacterial repetitive
      intergenic consensus sequence PCR (ERIC-PCR) for the typing of the species
      Tenacibaculum maritimum, Tenacibaculum soleae and Tenacibaculum discolor was
      evaluated. Moreover, molecular and proteomic techniques were used to assess
      variability among strains belonging to different serotypes, as well as isolated
      from different host species and geographical areas. Slide agglutination and dot
      blot assays demonstrated the lack of immunological relationships among
      Tenacibaculum species analyzed. The serotype O1 was predominant within T.
      maritimum isolates regardless of the fish species or geographical area. Two
      serotypes were distinguished within T. soleae isolates and at least one within T.
      discolor strains. Species- and strain-specific profiles were obtained from the
      analysis of T. maritimum, T. soleae and T. discolor by REP-PCR and ERIC-PCR,
      demonstrating their potential as diagnostic tools. The genotyping analysis using
      both techniques showed genetic variability among the strains of each fish
      pathogenic Tenacibaculum species analysed. However, Tenacibaculum strains
      isolated from different host species or geographical areas or belonging to
      different serotypes produced REP and ERIC profiles with high similarity. Analysis
      by MALDI-TOF-MS of the T. maritimum strains could not detect any serotype
      identifying biomarkers. Serotype-specific mass peaks were found for the serotypes
      O1 and O2 of T. soleae and for the serotype O1 of T. discolor. However, no
      relationships between the proteomic profiles and the source of isolation of the
      strains were obtained for any of the Tenacibaculum species analysed in this
      study.

PMID- 29453637
TI  - Cough hypersensitivity in patients with obstructive sleep apnea hypopnea
      syndrome.
AB  - PURPOSE: The purpose of this study was to investigate cough hypersensitivity and
      its potential mechanisms in patients with obstructive sleep apnea hypopnea
      syndrome (OSAHS). METHODS: Fifteen OSAHS patients, 12 simple snoring patients,
      and 15 healthy volunteers received cough sensitivity test and induced sputum
      cytology. Cough thresholds C2 and C5 (the minimum of capsaicin inducing >= 2 and
      >= 5 coughs, respectively), total cell count, cell differentials and the levels
      of bradykinin, histamine, prostaglandin E2, substance P, calcitonin gene-related
      peptide, pepsin, and interleukin-2 in the induced sputum detected by enzyme
      linked immunosorbent assay were compared. The linear correlation between lgC2 and
      lgC5 and apnea hypopnea index, cell differentials, and inflammatory mediators in
      the induced sputum was calculated in OSAHS patients. RESULTS: OSAHS patients
      presented with a significant lower C2 and C5 (P < 0.01), increased lymphocyte but
      decreased macrophage and neutrophil proportions in the induced sputum (P < 0.01),
      and higher contents of substance P, calcitonin gene-related peptide and
      interleukin-2 (P < 0.01) but similar levels of bradykinin, pepsin, prostaglandin
      E2, and histamine (P > 0.05) in the supernatant of induced sputum, when compared
      with simple snoring patients and healthy volunteers. However, theses variable
      were comparable between simple snoring patients and healthy volunteers (P >
      0.05). Finally, lgC2 or lgC5 was negatively related to apnea hypopnea index,
      lymphocyte percentage, and the levels of substance P, calcitonin gene-related
      peptide or interleukin-2 in the sputum (P < 0.01). There was a positive linear
      correlation between lymphocyte percentage and interleukin-2 level in the induced
      sputum (r = 0.63, P = 0.00). CONCLUSION: OSAHS patients have a predisposition of
      cough hypersensitivity associated with airway inflammation.

PMID- 29453636
TI  - Assessment of oximetry-based statistical classifiers as simplified screening
      tools in the management of childhood obstructive sleep apnea.
AB  - PURPOSE: A variety of statistical models based on overnight oximetry has been
      proposed to simplify the detection of children with suspected obstructive sleep
      apnea syndrome (OSAS). Despite the usefulness reported, additional thorough
      comparative analyses are required. This study was aimed at assessing common
      binary classification models from oximetry for the detection of childhood OSAS.
      METHODS: Overnight oximetry recordings from 176 children referred for clinical
      suspicion of OSAS were acquired during in-lab polysomnography. Several training
      and test datasets were randomly composed by means of bootstrapping for model
      optimization and independent validation. For every child, blood oxygen saturation
      (SpO2) was parameterized by means of 17 features. Fast correlation-based filter
      (FCBF) was applied to search for the optimum features. The discriminatory power
      of three statistical pattern recognition algorithms was assessed: linear
      discriminant analysis (LDA), quadratic discriminant analysis (QDA), and logistic
      regression (LR). The performance of each automated model was evaluated for the
      three common diagnostic polysomnographic cutoffs in pediatric OSAS: 1, 3, and 5
      events/h. RESULTS: Best screening performances emerged using the 1 event/h cutoff
      for mild-to-severe childhood OSAS. LR achieved 84.3% accuracy (95% CI 76.8-91.5%)
      and 0.89 AUC (95% CI 0.83-0.94), while QDA reached 96.5% PPV (95% CI 90.3-100%)
      and 0.91 AUC (95% CI 0.85-0.96%). Moreover, LR and QDA reached diagnostic
      accuracies of 82.7% (95% CI 75.0-89.6%) and 82.1% (95% CI 73.8-89.5%) for a
      cutoff of 5 events/h, respectively. CONCLUSIONS: Automated analysis of overnight
      oximetry may be used to develop reliable as well as accurate screening tools for
      childhood OSAS.

PMID- 29453635
TI  - Monitoring of erlotinib in pancreatic cancer patients during long-time
      administration and comparison to a physiologically based pharmacokinetic model.
AB  - PURPOSE: In this study, a therapeutic drug monitoring (TDM) of erlotinib in
      pancreatic cancer patients was performed over 50 weeks to reveal possible
      alterations in erlotinib plasma concentrations. Additionally, a physiologically
      based pharmacokinetic (PBPK) model was created to assess such variations in
      silico. METHODS: Patients with advanced pancreatic cancer received a
      chemotherapeutic combination of 100 mg erlotinib q.d., 500-900 mg capecitabine
      b.d. and 5 mg/kg bevacizumab q.2wks. Samples were analyzed by HPLC and the
      results were compared to a PBPK model, built with the software GastroPlusTM and
      based on calculated and literature data. RESULTS: The erlotinib plasma
      concentrations did not show any accumulation, but displayed a high inter-patient
      variability over the whole investigated period. Trough plasma concentrations
      ranged from 0.04 to 1.22 ug/ml after day 1 and from 0.01 to 2.4 ug/ml in the long
      term assessment. 7% of the patients showed concentrations below the necessary
      activity threshold of 0.5 ug/ml during the first week. The impact of some co
      variates on the pharmacokinetic parameters Cmax and AUC0-24 were shown in a PBPK
      model, including food effects, changes in body weight, protein binding or liver
      function and the concomitant intake of gastric acid reducing agents (ARAs).
      CONCLUSION: This study presents the approach of combining TDM and PBPK modeling
      for erlotinib, a drug with a high interaction potential. TDM is an important
      method to monitor drugs with increased inter-patient variability, additionally,
      the PBPK model contributed valuable insights to the interaction mechanisms
      involved, resulting in an effective combination from a PK perspective to ensure a
      safe treatment.

PMID- 29453638
TI  - Effects of CPAP therapy on cognitive and psychomotor performances in patients
      with severe obstructive sleep apnea: a prospective 1-year study.
AB  - STUDY OBJECTIVES: We prospectively investigated the effects of continuous
      positive airway pressure (CPAP) on long-term cognitive and psychomotor
      performances, and excessive daytime sleepiness in severe obstructive sleep apnea
      (OSA) patients. METHODS: A total of 40 patients were recruited and 23 patients
      with severe OSA fully completed the study protocol to investigate the effects of
      CPAP therapy on psychomotor performance at 1, 3, and 6 months and 1 year
      following initiation of the therapy. Psychomotor CRD-series tests measuring
      reaction times of light stimulus perception, solving simple arithmetic
      operations, and complex psychomotor limb coordination, were used in this study.
      The data collected following CPAP therapy were compared to baseline values prior
      to the CPAP treatment for each patient. RESULTS: All of the measured variables
      improved following CPAP treatment. However, the most pronounced effect was
      observed in improvement of reaction times to complex psychomotor limb
      coordination test (p < 0.05). Self-reported evaluation of excessive daytime
      sleepiness measured by Epworth Sleepiness Scale (ESS) showed significant decrease
      from 10.0 +/- 1.1 before to 3.5 +/- 0.5 (p < 0.001), after 1 year on CPAP
      therapy. CONCLUSIONS: The CPAP therapy improved cognitive and psychomotor
      performance on CRD-series tests with the most significant improvement observed in
      complex psychomotor limb coordination of severe OSA patients.

PMID- 29453639
TI  - Upper airway obstruction induced by non-invasive ventilation using an oronasal
      interface.
AB  - BACKGROUND: On initiation of long-term non-invasive ventilation (NIV),
      intermittent upper airway obstruction has rarely been described as possibly
      treatment-induced. Inspiratory pressure effects and the use of an oronasal
      interface may promote obstructive events in some patients with neuromuscular
      disease (NMD) and amyotrophic lateral sclerosis (ALS) in particular. METHODS: We
      evaluated clinical data from 212 patients in whom NIV was initiated using an
      oronasal mask. Treatment-induced upper airway obstruction (TAO) was defined as an
      AHI > 5/h along with a relative increase of the AHI in the first treatment night
      compared to diagnostic sleep studies. RESULTS: Prevalence of TAO was 14.2% in the
      entire cohort, 17.0% in patients with NMD (n = 165), 20.4% in the ALS subgroup (n
      = 93), and 4.3% in non-NMD patients (n = 47). Fixed expiratory positive airway
      pressure (EPAP, n = 192) was significantly correlated with AHI reduction (r =
      0.50; p < 0.001). The inspiratory-expiratory pressure interval (?PAP, n = 191)
      showed inverse correlation with the AHI change achieved in the first treatment
      night (r = - 0.28; p < 0.001). However, ?PAP and the effective pressure range
      between EPAP and the highest inspiratory PAP achieved were not predictive of TAO.
      In patients with ALS, TAO was associated with better bulbar function. Study
      results were limited by initial EPAP being significantly lower in NMD patients
      reflecting that sleep apnea was less frequent and severe in this subgroup.
      CONCLUSIONS: Initiation of NIV using an oronasal interface may be associated with
      TAO in a subset of patients. Since both EPAP and ?PAP appear to play a causative
      role, careful titration of ventilator settings is recommended.

PMID- 29453640
TI  - Effect of semi-rapid maxillary expansion in children with obstructive sleep apnea
      syndrome: 5-month follow-up study.
AB  - BACKGROUND: The purpose of this study was to investigate the effect of semi-rapid
      maxillary expansion (SRME) orthodontic treatment on biomarkers and respiratory
      parameters in children with obstructive sleep apnea syndrome (OSAS) and maxillary
      transverse deficiency. METHODS: Thirty children with OSAS were included in this
      study. Fifteen children were enrolled as control, and 15 children were subjected
      to SRME orthodontic treatment method for 5 months. Beside respiratory parameters,
      pharyngeal area, dental arch, and postero-anterior widths and the levels of OSAS
      biomarkers in serum and urine were measured. RESULTS: Pharyngeal airway space,
      dental arch, and postero-anterior widths were increased after SRME treatment.
      Sleep tests showed a decrease in the apnea-hypopnea index (AHI) after 5-month
      control/treatment duration. Serum kallikrein (KLK)1 levels decreased
      significantly in the treatment group. There was a significant increase in serum
      orosomucoid (ORM)2 levels and a decrease in urine perlecan levels in the control
      group after a 5-month follow-up. A significant negative correlation between serum
      ORM2, perlecan, gelsolin, and KLK1 levels and intercanin width, as well as
      between serum ORM2 and KLK1 levels and intermolar width, was observed.
      CONCLUSIONS: SRME treatment can be considered as a useful approach in children
      with OSAS. A further investigation of OSAS-related biomarkers and their
      relationship with sleep and orthodontic parameters is needed for providing easier
      and reliable modulatory strategies in the treatment of OSAS.

PMID- 29453641
TI  - Factor Structure and Psychometric Properties of the Thoughts About Psychotherapy
      Survey in a Parent Sample.
AB  - Researchers have noted that treatment fearfulness (e.g., embarrassment or
      negative attitudes) causes individuals to avoid seeking therapy. The purpose of
      this study was to examine the psychometric properties of the Thoughts About
      Psychotherapy Survey (TAPS; Kushner and Sher in Prof Psychol Res Prac 20(4):251
      257, 1989) in a sample of parents. This study also examined differences in
      therapy fears among parents with and without a history of using mental health
      services. Using a sample of 138 parents (87% female), findings indicated that a
      three factor structure of the TAPS was a good fit for the data. Furthermore, the
      scales demonstrated "good" internal consistency ranging from .86 to .93. Finally,
      parents that reported previous use of mental health services reported fewer
      treatment fears. Given these findings, the TAPS appears to be a valid measure to
      assess treatment fears among parents. Implications for research and practice will
      be discussed.

PMID- 29453642
TI  - Repeated closed reduction attempts of distal radius fractures in the emergency
      department.
AB  - INTRODUCTION: Repeated attempts of closed reduction of distal radius fractures
      (DRF) are performed in the emergency department setting to optimize fracture
      alignment and avoid surgery. The additional manipulation of the fracture may,
      however, increase dorsal comminution and lead to loss of reduction in the cast.
      This retrospective cohort study has investigated the effect of second reduction
      attempt on fracture alignment and comminution. MATERIALS AND METHODS: Six-hundred
      eighteen patients with DRF were treated in the medical center in 2007-2010.
      Seventy-six (12.3%) DRF who underwent two reductions were included in the study.
      Radiographs taken after the first and second reduction attempts were reviewed for
      changes in fracture alignment parameters (radial height, radial inclination,
      volar tilt) and dorsal comminution length. Patients were also followed
      retrospectively to determine the rates of secondary displacement in a cast.
      RESULTS: A second closed reduction attempt improved mean radial height by 1.43
      mm, mean radial inclination by 1.62 degrees  and mean volar tilt by 8.75 degrees
      . Mean dorsal comminution length increased by 1.6 mm. Of the 19 (25%) patients
      with acceptable alignments after two reduction attempts, follow-up radiographs
      were available for 12, which showed successful reduction in four cases (33.3 or
      5.2% of total 76 patients). CONCLUSIONS: A second closed reduction attempt
      improved immediate fracture alignment, but also worsened dorsal comminution. Only
      5.2% of patients who underwent two reduction attempts had an acceptable final
      alignment and did not require surgery. Increased dorsal comminution may further
      compromise fracture stability, complicate surgery and have negative effect on the
      postoperative course.

PMID- 29453643
TI  - The Effects of Mindfulness on Sexual Outcomes: The Role of Emotion Regulation.
AB  - Individuals higher in dispositional mindfulness, a quality of non-judgmental
      attention to the present moment, fare better than their less mindful counterparts
      on a wide range of psychological and interpersonal outcomes. However, remarkably
      little is known about the potential influence of dispositional mindfulness on
      sexual outcomes. Here we investigated whether dispositional mindfulness was
      associated with a range of sexual outcomes, including sexual satisfaction, sexual
      hyperactivation (heightened sexual desire and worry), sexual deactivation
      (suppression of sexual desire and behavior), and problematic pornography use. We
      also tested whether capacity for emotion regulation was the mechanism underlying
      the mindfulness-sexual outcome association. These hypotheses were tested in two
      samples: a sample of adults in a committed romantic relationship (N = 407) and a
      group of adults who were long-term single (N = 400). Across both samples,
      dispositional mindfulness predicted more adaptive sexual outcomes, and emotion
      regulation generally mediated these associations. Of particular importance, the
      positive effects of dispositional mindfulness on sexual outcomes appear to
      generalize across relationship statuses, with both partnered and long-term single
      individuals displaying a similar pattern of results. These findings highlight
      that high dispositional mindfulness may predict a range of positive sexual
      outcomes in both partnered and single individuals.

PMID- 29453644
TI  - Climate Change: A Call to Action for the Psychiatric Profession.

PMID- 29453645
TI  - Emphasis of FAS/FASL gene polymorphism in patients with non-muscle invasive
      bladder cancer.
AB  - BACKGROUND: Bladder cancer (BCa) is the seventh most common cancer among males
      worldwide. Some reliable markers in blood, urine, and tumor tissue, including
      clinicopathologic variables, molecular and inflammatory markers, gene
      polymorphisms, and tumor gene expression profiles are identified for predicting
      response to BCG immunotherapy in high-risk BCa patients. AIMS: We aimed to
      determine if FAS and FASL polymorphisms are associated with lack of response to
      BCG in patients with BCa. METHODS: The study included patients with primary non
      muscle invasive BCa that had undergone transurethral resection (TUR). Patient
      demographics, BCa characteristics, use of BCG immunotherapy, lack of response to
      BCG (if administered), BCa recurrence, and fatty acid synthetase/fatty acid
      syntethase ligand (FAS/FASL) polymorphisms were investigated. RESULTS: The study
      included 127 patients with primary BCa. Mean age of the 107 (84.3%) male and 20
      (15.7%) female patients was 59.3 +/- 13.2 years. Among the patients that received
      BCG immunotherapy, more FAS homozygous patients had BCa recurrence than FAS
      polymorphism-negative patients (P < 0.001) and more patients with homozygote FASL
      polymorphisms had BCa recurrence than those with heterozygous FASL polymorphisms
      and no polymorphism. CONCLUSION: Evaluation of FAS/FASL polymorphisms can predict
      lack of response to BCG immunotherapy and prevent the loss of valuable time
      before such alternative treatments as early cystectomy are initiated.

PMID- 29453646
TI  - Estimation of Radionuclide Concentrations and Average Annual Committed Effective
      Dose due to Ingestion for the Population in the Red River Delta, Vietnam.
AB  - Radioactivity concentrations of nuclides of the 232Th and 238U radioactive chains
      and 40K, 90Sr, 137Cs, and 239+240Pu were surveyed for raw and cooked food of the
      population in the Red River delta region, Vietnam, using alpha-, gamma
      spectrometry, and liquid scintillation counting techniques. The concentration of
      40K in the cooked food was the highest compared to those of other radionuclides
      ranging from (23 +/- 5) (rice) to (347 +/- 50) Bq kg-1 dw (tofu). The 210Po
      concentration in the cooked food ranged from its limit of detection (LOD) of 5
      mBq kg-1 dw (rice) to (4.0 +/- 1.6) Bq kg-1 dw (marine bivalves). The
      concentrations of other nuclides of the 232Th and 238U chains in the food were
      low, ranging from LOD of 0.02 Bq kg-1 dw to (1.1 +/- 0.3) Bq kg-1 dw. The
      activity concentrations of 90Sr, 137Cs, and 239+240Pu in the food were minor
      compared to that of the natural radionuclides. The average annual committed
      effective dose to adults in the study region was estimated and it ranged from
      0.24 to 0.42 mSv a-1 with an average of 0.32 mSv a-1, out of which rice, leafy
      vegetable, and tofu contributed up to 16.2%, 24.4%, and 21.3%, respectively. The
      committed effective doses to adults due to ingestion of regular diet in the Red
      River delta region, Vietnam are within the range determined in other countries
      worldwide. This finding suggests that Vietnamese food is safe for human
      consumption with respect to radiation exposure.

PMID- 29453647
TI  - New records and host associations of the tick Ixodes apronophorus and the first
      detection of Ehrlichia sp. HF in Romania.
AB  - Ixodes (Ixodes) apronophorus is a neglected tick species and its geographical
      distribution, host associations, and role as a disease vector are not well known.
      We collected I. apronophorus from several locations in Romania. Morphological
      identification of ticks was confirmed by analysis of 16S rDNA and 12S rDNA gene
      sequences. We report new host associations of I. apronophorus, which was
      collected from dogs, foxes, and a hare-all new hosts for this tick species in
      Romania. Furthermore, we report for the first time occurrence of Ehrlichia sp. HF
      in I. apronophorus. Ehrlichia sp. HF was identified by sequencing a part of the
      16S rDNA gene and was found in 16% (3/19) of the tested ticks. Ehrlichia sp. HF
      has not been previously reported in Eastern Europe and seems to have a much
      larger geographic distribution than previously known. Currently, it is unknown
      whether I. apronophorus is a competent vector for Ehrlichia sp. HF, or if the
      findings in this study represent infection in the hosts, namely dogs and fox.

PMID- 29453648
TI  - Supplemental diagnosis of Gyrodactylus fairporti Van Cleave, 1921 (Monogenea)
      from 1 month old black bullhead (Ameiurus melas) in riverside pools in Wisconsin.
AB  - Samples of Gyrodactylus fairporti Van Cleave, 1921 from young-of-the-year black
      bullhead (Ameiurus melas) stranded in riverside pools of the Black River (La
      Crosse County,) WI, USA, are used to supplement the species diagnosis, including
      new details on the marginal hook sickles, the male copulatory organ (MCO), and
      18S rRNA gene sequence data. The anchors of G. fairporti are relatively long and
      thin, 58.2 +/- 1.2 MUm in length; roots 15.5 +/- 1.0 MUm; shaft 38.1 +/- 1.5 MUm;
      point 31.3 +/- 1.5 MUm. The ventral bar is 19.4 +/- 0.4 MUm wide and 5.7 +/- 0.9
      MUm long, with small anterolateral processes, 2.0 +/- 0.6 MUm long, and an almost
      rectangular posterior shield 15.5 +/- 1.1 MUm in length. The marginal hooks are
      29.2 +/- 1.0 MUm long, with the handle 23.9 +/- 1.2 MUm in length. These
      measurements are similar to those reported from Iowa and Alabama, with the
      additional observation of the anchor point bending outwardly halfway along its
      length. The marginal hook sickle blade leaves the base angled ventrally away from
      the longitudinal axis; the sickle point is short; the toe has a rounded shelf and
      the heel is small, thin, and rounded. The MCO has eight small spines, two large
      ones laterally and the others of various lengths, with two of the smallest spines
      being slightly out-of-line compared with all the others. The taxonomy of G.
      fairporti is compared to Gyrodactylus ictaluri Rogers, 1967 and G. nebulosus
      Kritsky & Mizelle, 1967, the other two species known from captive and wild
      ictalurids endemic to North America. The three species all have a relatively
      compact ventral bar with short anterolateral processes, a short almost
      rectangular ventral bar membrane, an MCO with up to eight small spines of varying
      length, and a hook sickle angled ventrally. Diagnostically, the species are
      readily identified by the total length and shape of the anchors. G. fairporti
      bears the longest (53-65 MUm) and most slender anchors of the trio, G. nebulosus
      intermediate (49-51 MUm) and G. ictaluri with the shortest and stoutest (40-45
      MUm) of these species. A BLAST search of a partial (413 bp) 18S rRNA gene showed
      the highest similarity with Gyrodactylus sp. reported from Ameiurus nebulosus
      (Siluriformes) in Ontario.

PMID- 29453649
TI  - Reinereins A and B, new onocerane triterpenoids from Reinwardtiodendron cinereum.
AB  - Bioactivity guided separation of Reinwardtiodendron cinereum barks methanol
      extract led to the isolation of two new onocerane triterpenoids, reinereins A and
      B (1 and 2), together with three known onocerane triterpenoids. Their structures
      were elucidated on the basis of NMR spectroscopic data. In vitro cytotoxic
      activities of the isolated compounds against several type of cancer cells were
      evaluated.

PMID- 29453650
TI  - Atmospheric PM2.5 Mercury in the Metropolitan Area of Mexico City.
AB  - In this study, atmospheric mercury concentration in airborne particulate matter
      with an aerodynamic diameter <= 2.5 um (PM2.5) was analyzed by ICP-MS. Samples
      were collected in the Mexico City Metropolitan Area (MCMA), during 2013, in five
      locations, Northwest, Northeast (NE), Central, Southwest and Southeast, along
      three seasons: dry warm, rainy, and dry cold (DC). It can be observed that NE
      shows the highest mercury concentration (p < 0.05), where pollution events were
      identified. The seasonal distribution shows that samples collected during DC
      present the highest concentration (p < 0.05). These results are in agreement with
      the distribution of important mercury industrial sources located in the northern
      urban area as well with the temperature and wind conditions during 2013. The
      comparison of data obtained in this work with those of similar previous studies
      clearly indicates a decrease, between 2006 and 2013, of mercury content in PM2.5
      collected in MCMA.

PMID- 29453651
TI  - Neurotrophins in Asthma.
AB  - PURPOSE OF REVIEW: Asthma is a chronic airway disease that affects more than 300
      million people worldwide. Current treatment focuses on symptomatic relief by
      temporally dampening inflammation and relaxing the airway. Novel combative
      strategies against asthma and hopefully a cure are yet to be developed. The goal
      of this review is to summarize recent literature on neurotrophins (NTs) in
      experimental models and clinical settings of asthma research. RECENT FINDINGS: We
      highlight studies of early phases of asthma that collectively reveal a profound
      impact of elevated NT levels following initial detrimental insults on long-term
      airway dysfunction. We hope this review will foster insights into the complex
      interaction between NTs, nerves, immune cells, and airway structural cells during
      a critical time window of development and disease susceptibility. Future studies
      are required to better understand the role of NTs in asthma pathophysiology and
      to evaluate whether NTs and their receptors may serve as new drug targets.

PMID- 29453652
TI  - Significance of the nonneoplastic renal parenchymal findings in robotic partial
      nephrectomy series.
AB  - AIM: To describe the pathological characteristics of the peritumoral non
      neoplastic renal parenchyma (NNRP) and to investigate their impact on long-term
      renal function after partial nephrectomy. MATERIALS AND METHODS: In our
      institutional robotic partial nephrectomy database, we identified 394 cases with
      pathological assessment of the NNRP and long-term postoperative renal functional
      follow-up. The NNRP was classified as normal (healthy renal parenchyma) or
      abnormal, based on the presence of arteriosclerosis, glomerulosclerosis,
      interstitial fibrosis, interstitial inflammation, and/or tubulopapillary
      hyperplasia. The primary outcome was a >= 20% decline in estimated glomerular
      filtration rate (eGFR) at 6 and 12 months after surgery. Multivariable analysis
      was used to assess the association between NNRP and eGFR decline, with adjustment
      for demographic, clinical, and tumor factors. RESULTS: Overall, 250 (63.5%)
      pathological specimens had abnormal NNRP features. The most prevalent isolated
      benign pathological feature was glomerulosclerosis (18.0%), followed by
      arteriosclerosis (16.8%), interstitial inflammation (12.4%), interstitial
      fibrosis (1.2%), and tubulopapillary hyperplasia (0.4%). The abnormal NNRP group
      was associated with older age (p = .01), preoperative diabetes mellitus (p =
      .01), and preoperative hypertension (p = .01). The preoperative eGFR was
      significantly lower in the abnormal NNRP group (p = .01). NNRP abnormalities were
      not significantly associated with eGFR decline at either 6 or 12 months. The only
      independent predictor of eGFR decline was warm ischemia time (p = .01), and this
      association was only observed at 12 months. CONCLUSION: NNRP features are
      associated with preoperative comorbidities and lower baseline eGFR; however, they
      are not independent predictors of long-term renal functional preservation after
      partial nephrectomy.

PMID- 29453653
TI  - Tight interplay in early pregnancy between follistatin and anti-mullerian hormone
      in women with polycystic ovarian syndrome (PCOS).
AB  - PURPOSE: Follistatin levels increase during the course of pregnancy and may play
      a role in ovarian arrest, reflected by the simultaneous decrease of anti
      mullerian-hormone (AMH) levels. The aim of the study was to investigate AMH and
      follistatin levels during the hormonal window at the beginning of pregnancy.
      Since both parameters are described as deregulated in polycystic ovarian syndrome
      (PCOS), subgroup analysis of PCOS patients may additionally elucidate their
      interplay and effects on ovarian activity. METHODS: Serum samples were
      retrospectively analyzed using the AMH Gen II ELISA and the Human Follistatin
      Quantikine ELISA Kit. Samples were collected longitudinally from 57 patients (32
      with PCOS and 25 controls) before conception and during the first trimester. In
      18 patients, measurements from the early and the late first trimester were
      available. Potential associations of AMH and follistatin levels with PCOS-related
      parameters were compared between the subgroups as well as longitudinally before
      and in the first trimester of pregnancy. For statistical analysis, the Spearman's
      correlation, Wilcoxon test, t test, Friedman test and multiple linear regression
      analysis was performed. RESULTS: In contrast to AMH, follistatin levels differed
      not between controls and PCOS patients before and in pregnancy. In both
      subgroups, AMH levels significantly decreased and follistatin levels
      significantly increased in longitudinally performed measurements before
      conceiving and in the first trimester of pregnancy. CONCLUSION: Follistatin
      levels are not suited as a biomarker for PCOS, but could be involved in
      suppressing ovarian activity, as reflected by AMH levels at the beginning of
      pregnancy.

PMID- 29453654
TI  - Uterine electrical activity, oxytocin and labor: translating electrical into
      mechanical.
AB  - PURPOSE: Uterine activity plays a crucial role in labor, especially when utero
      tonic materials are administered. We aimed to determine the electrical
      responsiveness of the uterine musculature to labor augmentation with oxytocin
      using electrical uterine myography (EUM) technology, and to assess whether the
      kinetics of the EUM device may serve as a predictor for successful vaginal
      delivery. METHODS: EUM prospectively measured electrical uterine activity in
      women with singleton gestations at term (>= 37 + 0 weeks) undergoing labor
      augmentation by oxytocin administration. The results were reported as the EUM
      index, which represented the mean electrical activity in 10-min intervals and
      measured in units of microwatt per second (mW/s). Measurements were performed at
      least 30 min before oxytocin initiation and until at least four contractions per
      10 min were recorded by standard tocodynamometry. The delta EUM index was defined
      as the difference between the mean EUM index before and after the initiation of
      oxytocin. RESULTS: The mean EUM index increased significantly during oxytocin
      augmentation in all the parturients (P < 0.001). Mean and minimum (but not
      maximum) uterine electrical activity during oxytocin infusion correlated with the
      baseline uterine activity. The delta EUM index was not significantly affected by
      demographic or obstetric parameters. There was no correlation between the delta
      EUM index and time to delivery or the mean EUM index during oxytocin
      administration and time to delivery. CONCLUSIONS: Uterine electrical activity as
      evaluated by EUM is significantly intensified following oxytocin administration,
      regardless of obstetrical characteristics, and is correlated with the baseline
      uterine electrical activity prior to oxytocin infusion.

PMID- 29453655
TI  - Proteomic and genomic responses of plants to nutritional stress.
AB  - Minerals or trace elements in small amount are essential nutrients for every
      plant, but when the internal concentration exceeds the threshold, these essential
      elements do create phytotoxicity. Plant responses to elemental stresses are very
      common due to different anthropogenic activities; however it is a complex
      phenomenon with individual characteristics for various species. To cope up with
      the situation, a plant produces a group of strategies both in proteomic and
      genomic level to overcome it. Controlling the metal stress is known to activate a
      multigene response resulting in the changes in various proteins, which directly
      affects almost all biological processes in a living cell. Therefore, proteomic
      and genomic approaches can be useful for elucidating the molecular responses
      under metal stress. For this, it is tried to provide the latest knowledge and
      techniques used in proteomic and genomic study during nutritional stress and is
      represented here in review form.

PMID- 29453656
TI  - The ferroportin-ceruloplasmin system and the mammalian iron homeostasis machine:
      regulatory pathways and the role of lactoferrin.
AB  - In the last 20 years, several new genes and proteins involved in iron metabolism
      in eukaryotes, particularly related to pathological states both in animal models
      and in humans have been identified, and we are now starting to unveil at the
      molecular level the mechanisms of iron absorption, the regulation of iron
      transport and the homeostatic balancing processes. In this review, we will
      briefly outline the general scheme of iron metabolism in humans and then focus
      our attention on the cellular iron export system formed by the permease
      ferroportin and the ferroxidase ceruloplasmin. We will finally summarize data on
      the role of the iron binding protein lactoferrin on the regulation of the
      ferroportin/ceruloplasmin couple and of other proteins involved in iron
      homeostasis in inflamed human macrophages.

PMID- 29453657
TI  - The effect of L-carnitine supplementation on serum leptin concentrations: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - PURPOSE: The actual effects of L-carnitine administration on leptin serum level
      is inconsistent. In order to assess the efficacy of L-carnitine supplementation
      on serum leptin we conducted a meta-analysis of randomized controlled trials
      (RCTs). METHODS: Seven studies with 325 cases and 330 controls were included. The
      pooled weighted mean difference (WMD) was calculated by random-effects model. The
      heterogeneity across studies was evaluated by using Cochrane's Q and I2 tests. In
      addition, we carried out the metaninf command to test the effect of each
      individual study on the overall result. RESULTS: L-carnitine supplementation
      seemed to have no significant effect on serum leptin concentrations (WMD: -0.565
      ng/mL; 95% CI: -2.417 to 1.287, p = 0.550). However, between-study heterogeneity
      was higher across all studies (I2 = 84.3%, p < 0.0001). Subgroup analysis to find
      the sources of heterogeneity showed that L-carnitine dosage (g) ( < 2 g: I2 =
      00.0%, p = 0.408), and study population (diabetes: I2 = 46.7%, p = 0.153, and non
      diabetes: I2 = 15.1%, p = 0.317) were the potential sources of heterogeneity.
      Besides, a more significant reduction in serum leptin concentration was observed
      with a daily dose of >= 2 mg L-carnitine (WMD: -2.742 ng/mL; 95% CI: -3.039 to 
      2.444, p < 0.001), in diabetic patients (WMD: -2.946 ng/mL; 95% CI: -3.254 to 
      2.638, p < 0.001), and with intervention duration <12 weeks (WMD: -2.772 ng/mL;
      95% CI: -3.073 to -2.471, p < 0.001). CONCLUSION: L-carnitine consumption does
      not reduce serum leptin significantly. However, a significant effect on leptin
      was observed in diabetic patients and patients who received doses more than 3 mg
      per day in the course of <12 weeks.

PMID- 29453658
TI  - High-intensity focused ultrasound (HIFU) therapy for benign thyroid nodules
      without anesthesia or sedation.
AB  - BACKGROUND: Thermal ablation of thyroid nodules has gained momentum due to the
      possibility to avoid surgery. High-intensity focused ultrasound (HIFU) allows
      thermal treatment by energy ultrasound beam inside the targeted zone. Aim of our
      study was to evaluate the effects of HIFU treatment using Beamotion mode without
      anesthesia. METHODS: Since 2016, patients with normal thyroid function, benign
      thyroid nodules with diameter no larger than 4 cm, and presenting local
      discomfort and/or compressive symptoms were treated by HIFU. We performed
      Beamotion HIFU and did not use anesthesia. Nodule size and thyroid function were
      evaluated before HIFU and 6 and 12 months later. Complications to therapy and
      tolerability of patients were also recorded. According to local ethical
      committee, for this retrospective study formal consent was not required. RESULTS:
      The final series included 26 nodules from 26 patients with estimated volume of
      2.81 +/- 2.04 mL, treated by a power of 33.3 +/- 10.3 W/site and energy of 2.1 +/
      1.1 kJ. Nodules volume was significantly (p < 0.0001) reduced at 6 months of
      follow-up (1.83 +/- 1.63 mL), and further at 1 year (1.57 +/- 1.47 mL). Mean
      percentage of reduction over time of nodules was 48%. A 73% of patients described
      good comfort during treatment, 100% experienced good comfort just after therapy,
      and tolerability was high. No complications were recorded. At one 1 year of
      follow-up, 85% of subjects reported a reduction of local symptoms. CONCLUSIONS:
      HIFU therapy is effective in reducing size of thyroid nodules with major diameter
      below 4 cm and can be performed without anesthesia.

PMID- 29453659
TI  - Fracture risk in women with type II diabetes. Results from a historical cohort
      with fracture follow-up.
AB  - PURPOSE: To examine the independent association between type II diabetes and
      fracture risk in a population of predominantly postmenopausal women referred to a
      specialist clinic for osteoporosis evaluation. METHODS: Type II diabetes
      associated fracture risk were evaluated among to 229 patients with type II
      diabetes in a cohort of 6285 women followed on average (until major osteoporotic
      fracture (MOF), death or end of study) for 5.8 years. Information of fracture
      risk factors was obtained from a clinical database and from national registries.
      RESULTS: An elevated fracture risk was present. Prevalent fractures (43.7 vs.
      33.2%, p = 0.0010) and prevalent MOF (26.2 vs. 20.5% p = 0.038) were more common
      among patients with type II diabetes. The unadjusted incident fracture risk was
      increased with a higher relative risk of 42%. An elevated MOF hazard ratio was
      present (HR = 1.726, p = 0.0006). Adjustment for prevalent osteoporosis and other
      possible confounders did not change this finding (HR = 1.558, p = 0.0207).
      CONCLUSIONS: An association between type II diabetes and an increased risk of MOF
      primarily driven by an increased hip fracture risk was documented. This finding
      was independent of the presence of osteoporosis. Clinicians need to be aware of
      and adjust for these findings when evaluating patients with diabetes. Additional
      research examining pathophysiological mechanisms are needed.

PMID- 29453660
TI  - Verification of candidate microRNA markers for parathyroid carcinoma.
AB  - PURPOSE: Parathyroid carcinoma (PCa) is a rare endocrine malignancy with poor
      prognosis and is often difficult to accurately diagnose both before and after
      surgery. Dysregulated microRNA (miRNA) levels have been identified in PCa using a
      limited number of samples. The aim of the present study was to verify a group of
      miRNA markers in a new series of samples to explore their potential significance
      in PCa diagnosis. METHODS: A total of 58 tissue samples, including 17 PCa lesions
      and 41 sporadic parathyroid adenomas (PAds), were obtained from 56 primary
      hyperparathyroidism (pHPT) patients. Candidate miRNAs (miR-139-5p, miR-155-5p,
      miR-222-3p, miR-26b-5p, miR-296-5p, miR-30b-5p, miR-372-3p, miR-503-5p, miR-517c
      3p, miR-7-5p, and miR-126-5p) were quantified by TaqMan real-time quantitative
      PCR assays. RESULTS: Up-regulated miR-222 (p = 0.041) levels and down-regulated
      miR-139 (p = 0.003), miR-30b (p < 0.001), miR-517c (p = 0.038), and miR-126* (p =
      0.002) levels were found in PCa relative to PAd. Binary logistic regression
      analysis showed that miR-139 and miR-30b were the best diagnostic markers. The
      combination of miR-139 and miR-30b yielded an area under the receiver operating
      characteristic curve of 0.888. Additionally, serum calcium (r s  = -0.518, p <
      0.001), intact parathyroid hormone (iPTH) (r s  = -0.495, p < 0.001), and
      alkaline phosphatase (ALP) (r s  = -0.523, p < 0.001) levels were negatively
      correlated with miR-30b levels. CONCLUSIONS: miR-139, miR-222, miR-30b, miR-517c,
      and miR-126* were differentially expressed between PCa and PAd. The combined
      analysis of miR-139 and miR-30b may be used as a potential diagnostic strategy
      for distinguishing PCa from PAd.

PMID- 29453661
TI  - Maize water status and physiological traits as affected by root endophytic fungus
      Piriformospora indica under combined drought and mechanical stresses.
AB  - MAIN CONCLUSION: Under combined drought and mechanical stresses, mechanical
      stress primarily controlled physiological responses of maize. Piriformospora
      indica mitigated the adverse effects of stresses, and inoculated maize
      experienced less oxidative damage and had better adaptation to stressful
      conditions. The objective of this study was to investigate the effect of maize
      root colonization by an endophytic fungus P. indica on plant water status,
      physiological traits and root morphology under combined drought and mechanical
      stresses. Seedlings of inoculated and non-inoculated maize (Zea mays L., cv.
      single cross 704) were cultivated in growth chambers filled with moistened
      siliceous sand at a matric suction of 20 hPa. Drought stress was induced using
      PEG 6000 solution with osmotic potentials of 0, - 0.3 and - 0.5 MPa. Mechanical
      stress (i.e., penetration resistances of 1.05, 4.23 and 6.34 MPa) was exerted by
      placing weights on the surface of the sand medium. After 30 days, leaf water
      potential (LWP) and relative water content (RWC), root and shoot fresh weights,
      root volume (RV) and diameter (RD), leaf proline content, leaf area (LA) and
      catalase (CAT) and ascorbate peroxidase (APX) activities were measured. The
      results show that exposure to individual drought and mechanical stresses led to
      higher RD and proline content and lower plant biomass, RV and LA. Moreover,
      increasing drought and mechanical stress severity increased APX activity by about
      1.9- and 3.1-fold compared with the control. When plants were exposed to combined
      stresses, mechanical stress played the dominant role in controlling plant
      responses. P. indica-inoculated plants are better adapted to individual and
      combined stresses. The inoculated plants had greater RV, LA, RWC, LWP and proline
      content under stressful conditions. In comparison with non-inoculated plants,
      inoculated plants showed lower CAT and APX activities which means that they
      experienced less oxidative stress induced by stressful conditions.

PMID- 29453662
TI  - The overexpression of RXam1, a cassava gene coding for an RLK, confers disease
      resistance to Xanthomonas axonopodis pv. manihotis.
AB  - MAIN CONCLUSION: The overexpression of RXam1 leads to a reduction in bacterial
      growth of XamCIO136, suggesting that RXam1 might be implicated in strain-specific
      resistance. Cassava bacterial blight (CBB) caused by Xanthomonas axonopodis pv.
      manihotis (Xam) is a prevalent disease in all regions, where cassava is
      cultivated. CBB is a foliar and vascular disease usually controlled through host
      resistance. Previous studies have found QTLs explaining resistance to several Xam
      strains. Interestingly, one QTL called XM5 that explained 13% of resistance to
      XamCIO136 was associated with a similar fragment of the rice Xa21-resistance gene
      called PCR250. In this study, we aimed to further identify and characterize this
      fragment and its role in resistance to CBB. Screening and hybridization of a BAC
      library using the molecular marker PCR250 as a probe led to the identification of
      a receptor-like kinase similar to Xa21 and were called RXam1 (Resistance to Xam
      1). Here, we report the functional characterization of susceptible cassava plants
      overexpressing RXam1. Our results indicated that the overexpression of RXam1
      leads to a reduction in bacterial growth of XamCIO136. This suggests that RXAM1
      might be implicated in strain-specific resistance to XamCIO136.

PMID- 29453663
TI  - The rice "fruit-weight 2.2-like" gene family member OsFWL4 is involved in the
      translocation of cadmium from roots to shoots.
AB  - MAIN CONCLUSION: Heterogeneous expression of the rice genes "fruit-weight 2.2
      like" (OsFWL) affects Cd resistance in yeast, and OsFWL4 mediates the
      translocation of Cd from roots to shoots. Cadmium (Cd) induces chronic and toxic
      effects in humans. In a previous study (Xu et al. in Planta 238:643-655, 2013),
      we cloned the rice genes, designated OsFWL1-8, homologous to the tomato fruit
      weight 2.2. Here, we show that expression of genes OsFWL3-7 in yeast confers
      resistance to Cd. The Cd contents of OsFWL3-, -4-, -6- and -7-transformed Cd(II)
      sensitive yeast mutant ycf1 cells were strongly decreased compared with those of
      empty vector, with the strongest resistance to Cd observed in cells expressing
      OsFWL4. Evaluation of truncated and site-directed mutation derivatives revealed
      that the CCXXG motifs near the second transmembrane region of OsFWL4 are involved
      in Cd resistance in yeast. Real-time PCR analysis showed that OsFWL4 expression
      was induced by CdCl2 stress in rice seedlings. Compared with WT plants, the Cd
      contents in the shoots of RNAi mediated OsFWL4 knockdown plants were
      significantly decreased, and Cd translocation from roots to shoots was reduced.
      According to bimolecular fluorescence complementation, yeast two-hybrid and
      Western-blotting assays, the OsFWL4 protein forms homo-oligomers. These results
      suggest that OsFWL4 might act directly as a transporter and is involved in the
      translocation of Cd from roots to shoots in rice.

PMID- 29453664
TI  - Analysis of transactivation potential of rice (Oryza sativa L.) heat shock
      factors.
AB  - MAIN CONCLUSION: Based on yeast one-hybrid assays, we show that the presence of C
      terminal AHA motifs is not a prerequisite for transactivation potential in rice
      heat shock factors. Transcriptional activation or transactivation (TA) of heat
      stress responsive genes takes place by binding of heat shock factors (Hsfs) to
      heat shock elements. Analysis of TA potential of thirteen rice (Oryza sativa L.)
      Hsfs (OsHsfs) carried out in this study by yeast one-hybrid assay showed that
      OsHsfsA3 possesses strong TA potential while OsHsfs A1a, A2a, A2b, A4a, A4d, A5,
      A7b, B1, B2a, B2b, B2c and B4d lack TA potential. From a near complete picture of
      TA potential of the OsHsf family (comprising of 25 members) emerging from this
      study and an earlier report from our group (Mittal et al. in FEBS J 278(17):3076
      3085, 2011), it is concluded that (1) overall, six OsHsfs, namely A3, A6a, A6b,
      A8, C1a and C1b possess TA potential; (2) four class A OsHsfs, namely A3, A6a,
      A6b and A8 have TA potential out of which A6a and A6b contain AHA motifs while A3
      and A8 lack AHA motifs; (3) nine class A OsHsfs, namely A1a, A2a, A2b, A2e, A4a,
      A4d, A5, A7a and A7b containing AHA motif(s) lack TA function in the yeast assay
      system; (4) all class B OsHsfs lack AHA motifs and TA potential (B4a not
      analyzed) and (5) though all class C OsHsf members lack AHA motifs, two members
      C1a and C1b possess TA function, while one member C2a lacks TA potential (C2b not
      analyzed). Thus, the presence or absence of AHA motif is possibly not the only
      factor determining TA potential of OsHsfs. Our findings will help to identify the
      transcriptional activators of rice heat shock response.

PMID- 29453665
TI  - Klaus Apel (1942-2017): a pioneer of photosynthesis research.
AB  - We present here a Tribute to Klaus Apel (1942-2017), a photosynthesis pioneer-an
      authority on plant molecular genetics-in five parts. The first section is a
      prologue. The second section deals with a chronological discussion of Apel's
      research life, prepared by the editor Govindjee; it is based on a website article
      at the Boyce Thompson Institute (BTI) by Patricia Waldron (
      https://btiscience.org/explore-bti/news/post/bti-says-goodbye-klaus-apel/ ), as
      approved for use here by Keith C. Hannon and David Stern of BTI. The third
      section, which focuses on Apel's pioneering work on singlet oxygen-mediated
      EXECUTER-dependent signaling in plants, is written by two of us (J-DR and CK).
      The fourth section includes three selected reminiscences, one from BTI and two
      from ETH (Eidgenossische Technische Hochschule). This tribute ends with section
      five, which is a very brief presentation of Klaus Apel's personal life, by Wiebke
      Apel.

PMID- 29453666
TI  - Comments on "A Mathematical Study to Control Visceral Leishmaniasis: An
      Application to South Sudan".
AB  - Deterministic (ordinary differential equation) models for the transmission
      dynamics of vector-borne diseases that incorporate disease-induced death in the
      host(s) population(s) are generally known to exhibit the phenomenon of backward
      bifurcation (where a stable disease-free equilibrium of the model coexists with a
      stable endemic equilibrium when the associated reproduction number of the model
      is less than unity). Further, it is well known that, in these models, the
      phenomenon of backward bifurcation does not occur when the disease-induced death
      rate is negligible (e.g., if the disease-induced death rate is set to zero). In a
      recent paper on the transmission dynamics of visceral leishmaniasis (a disease
      vectored by sandflies), titled "A Mathematical Study to Control Visceral
      Leishmaniasis: An Application to South Sudan," published in Bulletin of
      Mathematical Biology, Vol. 79, Pages 1110-1134, 2017, Ghosh et al. (2017) stated
      that their deterministic model undergoes a backward bifurcation even when the
      disease-induced mortality in the host population is set to zero. This result is
      contrary to the well-established theory on the dynamics of vector-borne diseases.
      In this short note, we illustrate some of the key errors in the Ghosh et al.
      (2017) study.

PMID- 29453667
TI  - Dissolved organic matter characteristics along sabo dammed streams based on
      ultraviolet visible and fluorescence spectral properties.
AB  - Changes in dissolved organic matter (DOM) characteristics were investigated in
      two mountainous streams with closed-type sabo dams. Surface water was collected
      from four stations along the two mountainous streams and analyzed using
      ultraviolet-visible spectrophotometry and excitation-emission fluorescence matrix
      (EEM) methods. Optical properties of DOM indicated an increase in molecular
      weight and aromaticity at stations near the sabo dams. Average spectral ratio
      values were low before and after the dam (i.e., < 0.72) compared to other
      sections of the stream. Specific ultraviolet absorbance (SUVA254) increased in
      the vicinities of the dams. While chromophoric DOM characteristics from two sites
      were influenced by the dam, fluorescence components, however, did not show
      notable changes around dams. Instead, the three chromophoric components
      distinguished by EEM-parallel factor analysis, that is, humic-like (C1 and C2)
      and protein-like (C3) increase along the stream. Fulvic-like component (C1) had a
      high fluorescence intensity at all stations; all the three components were more
      abundant in the downstream section. Chromophoric DOM properties varied along the
      stream based on alterations in molecular size and aromaticity. Using multivariate
      analysis, the studied sites were grouped into three clusters related to sabo dams
      and other activities. We conclude that sabo dams modify DOM characteristics which
      influence the behavior of DOM transported along the stream.

PMID- 29453668
TI  - Netarsudil Ophthalmic Solution 0.02%: First Global Approval.
AB  - Netarsudil ophthalmic solution 0.02% (hereafter referred to as netarsudil 0.02%)
      [Rhopressa(r)] is a Rho-associated protein kinase inhibitor that is thought to
      lower intraocular pressure (IOP) by increasing aqueous humour outflow through the
      trabecular meshwork. It has been developed by Aerie Pharmaceuticals and was
      recently approved in the USA for the reduction of elevated IOP in patients with
      open-angle glaucoma or ocular hypertension. The recommended dosage is one drop in
      the affected eye(s) once daily in the evening. Phase III development in the EU
      and phase II development in Japan are underway for this indication. This article
      summarizes the milestones in the development of netarsudil 0.02% leading to this
      first approval for the reduction of elevated IOP in patients with open-angle
      glaucoma or ocular hypertension.

PMID- 29453669
TI  - Physical Training and Cardiac Rehabilitation in Heart Failure Patients.
AB  - Regardless of advances in medical and interventional treatment of cardiovascular
      disease (CVD), a limited number of patients attend a cardiac rehabilitation (CR)
      programme on a regular basis. Due to modern therapies more individuals will be
      surviving an acute cardiovascular event, but the expected burden of chronic heart
      failure will be increasing worldwide.However, both in high- and low-income
      countries, secondary prevention after an acute myocardial infarction or stroke
      has been implemented in less than a half of eligible patients.Combined
      interventions are still needed to reduce decompensations, hospitalizations and
      mortality in heart failure patients from any origin. In addition to medical
      treatments, regular exercise has been demonstrated to improve metabolic and
      hemodynamic conditions in both asymptomatic risk factor carriers and cardiac
      patients. Risk factor control and exercise should gather together for an
      effective management of patients.Exercise-based training is a core component of
      primary and secondary prevention. It should involve healthy carriers of
      cardiovascular risk factors, and patients with cardiomyopathy as well. The
      supposed attenuated effect of CR in the era of advanced revascularization and
      structural interventions is due to the heterogeneity of training models and
      physical training in the literature. Moreover, lifestyle modification, psycho
      social challenges and patient's compliance are potential confounders.In this
      chapter the most recent evidences about training modalities and potential benefit
      of CR in heart failure patients are discussed.

PMID- 29453670
TI  - Incidence and Drug Resistance of Zoonotic Mycobacterium bovis Infection in
      Peshawar, Pakistan.
AB  - Prevalence of zoonotic Mycobacterium bovis (bTB) disease in human population is
      underreported from the North of Pakistan. Here, we report on the proportion of
      human bTB disease among the overall TB patients, drug resistance pattern of bTB
      isolates, and knowledge, attitude, and practices (KAP)-based analysis of bTB
      disease. For this purpose, sputum samples from a total of 300 clinically
      diagnosed TB patients and 100 randomly selected school children suspected of
      pulmonary TB were processed by culture as well as polymerase chain reaction (PCR)
      for isolation, identification, and confirmation of Mycobacterium tuberculosis
      (mTB) and bTB species. Isolates of bTB were processed for drug susceptibility
      tests. Data on KAP regarding TB were obtained on a pretested questionnaire.
      Sputum-based PCR results indicated that 288/300 (96%) were confirmed as mTB,
      while 12/300 (4%) were found as bTB diseases. Interestingly, none of the school
      child was declared positive for either mTB or bTB. Notably, 274/300 (91.3%)
      positively cultured samples were identified as mTB, 13/300 (4.3%) as bTB, while
      5/300 (1.7%) as mixed containing both. Importantly, except one, all of the bTB
      isolates were found resistant to pyrazinamide. Surprisingly, most of the bTB
      isolates (~70%) were found resistant to a broad range of first- and second-line
      anti-TB drugs. SplitsTree and recombination analysis indicated no evidence of
      intergenic recombination. Finally, residence, occupation, presence of animals at
      home, and sleeping alongside animals were found significantly associated with
      occurrence of bTB disease. To the best of our knowledge, we report for the first
      time on the high (4%) burden of bTB disease in human TB patients in Peshawar,
      Pakistan.

PMID- 29453671
TI  - Comparative evaluation of pharmacokinetics and pharmacodynamics of insulin
      glargine (Glaritus(r)) and Lantus(r) in healthy subjects: a double-blind,
      randomized clamp study.
AB  - AIMS: The objective of the study was to compare the pharmacokinetic (PK) and
      pharmacodynamic (PD) properties of an insulin glargine formulation, Glaritus(r)
      (test) with the innovator's formulation Lantus(r) (reference) using the
      euglycemic clamp technique in a single-dose, double-blind, randomized, two
      sequences, four-period replicate crossover study in healthy volunteers (n = 40).
      METHODS: Subjects received subcutaneous administration of the insulin glargine
      (0.4 IU/kg) formulation at two occasions for test and reference and a 20% glucose
      solution was infused at variable rate to maintain euglycemia for 24 h. RESULTS:
      Both PK [area under the plasma concentration time curve (AUC0-24 h) and maximum
      insulin concentration (Cmax)] and PD endpoints [area under glucose infusion rate
      time curve (AUCGIR0-24) and maximum glucose infusion rate (GIRmax)] demonstrated
      bioequivalence of Glaritus to Lantus with the 90% confidence interval of
      geometric mean ratio of test to reference entirely contained within 0.80-1.25.
      Both formulations showed equivalent geometric least-square mean LSM value (0.08
      nmol/L) for Cmax. The geometric LSM AUC0-24 h value for Glaritus(r) (1.09 h
      nmol/L) was comparable to Lantus (1.05 h nmol/L). Median Tmax values were also
      identical (12 h for both), and median t1/2 values were also equal (18 h for
      both). For GIRTmax, the difference between the means for the two was not
      statistically significant. No AEs related to study formulations were reported,
      and both products were well tolerated. CONCLUSIONS: The test product (Glaritus)
      was found to be bioequivalent to the reference product (Lantus). CLINICAL TRIAL
      REGISTRATION NUMBER: CTRI/2015/06/005890; http://www.ctri.nic.in/ .

PMID- 29453672
TI  - The effect of n-3 PUFAs on circulating adiponectin and leptin in patients with
      type 2 diabetes mellitus: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - AIM: N-3 PUFAs can potentially influence levels of inflammatory and non
      inflammatory adipokines. Given the contradictory effects of n-3 PUFAs on serum
      levels of adipokines in type 2 diabetes, we conducted a systematic review and
      meta-analysis study of randomized placebo-controlled clinical trials that
      examined the effects of n-3 PUFAs on serum levels of leptin and adiponectin in
      patients with type 2 diabetes. METHODS: The electronic databases, without regard
      to language restrictions including PubMed/Medline, Google Scholar, SCOPUS and ISI
      Web of Science until August 2017, were used to identify randomized controlled
      trials that assessed the effect of n-3 PUFAs on serum leptin and adiponectin
      concentrations in type 2 diabetes. Outcomes were extracted based on the mean +/-
      SD as effect size at baseline and end of the intervention. Between-study
      heterogeneity was evaluated by the I2 estimates and their 95% CIs. Funnel plot
      asymmetry was used to investigate the existence of publication bias. Stata
      software and Review Manager were used for statistical data analysis. RESULTS:
      Data from 10 eligible articles involved 494 subjects with type 2 diabetes
      mellitus (intervention groups = 254 and control groups = 240), with age between
      44 and 70 years, treated with doses of 0.52-7.4 g/day n-3 PUFAs. Adiponectin
      concentration nonsignificantly increased by a MD = 0.17 ug/mL (95% CI - 0.11,
      0.44). Also, leptin concentration nonsignificantly reduced by a MD = - 0.31 ng/mL
      (95% CI - 0.69, 0.07). CONCLUSION: Plant and marine sources of n-3 PUFAs can
      modify serum leptin and adiponectin levels by increasing adiponectin and
      decreasing leptin levels in patients with type 2 diabetes. Due to some
      limitations in this study, further studies are needed to reach a definitive
      conclusion about the effect of n-3 PUFAs on the levels of leptin and adiponectin
      in T2DM.

PMID- 29453674
TI  - Contrast-enhanced ultrasonography of post-interventional hematoma: the bleeding
      mushroom is growing inside.
AB  - Catheter ablation is an effective treatment in patients with symptomatic atrial
      fibrillation. Complications are infrequent and usually resolve with minimal or no
      intervention, but active bleeding due to arterial injury during the vascular
      access can sometimes represent a life-threatening complication. Contrast-enhanced
      computed tomography is the standard technique to detect active bleeding, but it
      may not be immediately available. We report a case of iatrogenic hemorrhage after
      catheter ablation, in which contrast-enhanced ultrasonography played a decisive
      role in the recognition of active arterial bleeding due to injury to the right
      common femoral artery.

PMID- 29453673
TI  - Optical coherence tomography angiography discerns preclinical diabetic
      retinopathy in eyes of patients with type 2 diabetes without clinical diabetic
      retinopathy.
AB  - AIMS: To investigate changes in retinal vascular plexuses and choriocapillaris in
      patients with type 2 diabetes mellitus (DM2) without diabetic retinopathy (DR)
      and healthy controls using optical coherence tomography angiography (OCTA).
      METHODS: A total of 71 DM2 and 67 healthy control subjects were included. All
      subjects underwent OCTA examination (RTVue-XR Avanti; Optovue, Fremont, CA, USA).
      Average vessel density in superficial capillary plexus (SCP), deep capillary
      plexus (DCP) and choriocapillaris, parafoveal vessel density in SCP and DCP, FAZ
      area (mm2) in SCP, microaneurysms and capillary nonperfusion were taken into
      analysis. RESULTS: Parafoveal vessel density in both SCP and DCP decreased in the
      eyes without clinical DR compared to normal controls (p < 0.001). Diabetic
      patients with no signs of DR also had a significant reduction in average vessel
      density of SCP, DCP and choriocapillaris (p < 0.001, p < 0.001 and p = 0.006,
      respectively). No significant difference was found in FAZ area of SCP between DM2
      eyes and healthy controls (p = 0.253). The average vessel density of SCP and DCP
      is not correlated with HbA1c or serum creatinine in DM2 patients. Microaneurysms
      seen in OCTA but not in fundus examination were found in 8 out of the 71 (11.3%)
      diabetic eyes, and capillary nonperfusion was noted in 18 of 71 diabetic eyes.
      CONCLUSIONS: We demonstrated that OCTA can identify preclinical DR before the
      manifestation of clinically apparent retinopathy in diabetic eyes. DM2 patients
      without DR have SCP, DCP and choriocapillaris impairment. Our results suggested
      that OCTA might be a promising tool for regular screening of diabetic eyes for
      DR.

PMID- 29453675
TI  - Evaluation of carotid artery elasticity in patients with uremia by echo tracking.
AB  - PURPOSE: The purpose of this study was to compare the carotid artery wall
      elasticity between patients with uremia and controls using echo tracking (ET).
      METHODS: Ninety-three patients with uremia and 35 control subjects (Group A) were
      enrolled in this study. In the ET mode, the carotid artery elasticity parameters
      including stiffness index (beta), pressure-strain elasticity modulus (EP),
      arterial compliance (AC), and one-point pulse wave velocity (PWVbeta) were
      measured, and carotid intima-media thickness (IMT) was measured with B-mode
      ultrasonography. The patients were classified into three groups: Group B (normal
      IMT), Group C (thickened IMT), and Group D (one single atheroma plaque). RESULTS:
      beta, EP, and PWVbeta were significantly higher in Group B, C, and D (especially
      in group D) than those of the control group (P < 0.05), and there were
      significant differences between Group A and Group B, while AC was lower than in
      controls, but there were no statistically significant differences among the four
      groups. CONCLUSIONS: ET is a noninvasive method that can demonstrate a loss in
      carotid artery elasticity in uremia patients with normal IMT.

PMID- 29453676
TI  - Properties of bacterial communities attached to artificial substrates in a
      hypereutrophic urban river.
AB  - Bacterial communities of biofilms growing on artificial substrates were examined
      at two time periods (7 and 14 days) and two locations (lentic and lotic areas) in
      a hypereutrophic urban river of eastern China. Previous studies in this river
      network indicated that variations of microbial communities were the major factor
      affecting the distribution of antibiotic resistant genes highlighting the
      importance of understanding controls of microbial communities. Bacterial
      communities associated with biofilms were determined using epifluorescence
      microscopy and high-throughput sequencing. Results showed that sampling time and
      site had significant effects on the abundances of surface-associated bacteria. No
      significant differences were found in the number of surface-associated bacteria
      between two substrate types (filament vs. slide). Sequencing revealed microbial
      communities attached to artificial substrates in a hypereutrophic urban river
      were composed of 80,375 OTUs, and distributed in 47 phyla. Proteobacteria and
      Cyanobacteria/Chloroplast were the two dominant phyla, followed by
      Planctomycetes, Actinobacteria, Verrucomicrobia, Firmicutes and Bacteroidetes.
      Taxonomic composition showed ammonia-oxidizing microorganisms, fecal indicator
      bacteria and pathogens enriched in attached microbial communities, especially the
      ammonia-oxidizing Nitrosomonas bacteria. These results indicated that there were
      significant temporal and intra-river heterogeneity of attached microbial
      community structure, but no significant difference in community composition was
      detected between the two substrate types.

PMID- 29453677
TI  - Changes in medicine prescription following a medication review in older high-risk
      patients with polypharmacy.
AB  - Background The more (inappropriate) drugs a patient uses, the higher the risk of
      drug related problems. To reduce these risks, medication reviews can be
      performed. Objective To report changes in the prescribed number of (potentially
      inappropriate) drugs before and after performing a medication review in high-risk
      polypharmacy patients. A secondary objective was to study reasons for continuing
      potentially inappropriate drugs (PIDs). Setting Dutch community pharmacy and
      general medical practice. Methods A retrospective longitudinal intervention study
      with a pre-test/post-test design and follow-up of 1 week and 3 months was
      performed. The study population consisted of 126 patients with polypharmacy and
      with additional risk for drug related problems that underwent a medication review
      in five community pharmacies. The medication review was performed by the
      pharmacist in close cooperation with the general practitioner of each
      corresponding patient. Main outcome measure Number of (potentially inappropriate)
      drugs, and appropriateness of prescribed medicines. Results The average number of
      drugs a patient used 1 day before the review was 8.7 (SD = 2.9), which decreased
      (p < 0.05) to 8.3 (SD = 2.7) 1 week after the review, and to 8.4 (SD = 2.6) 3
      months after the review. The average number of PIDs was initially 0.6 (SD = 0.8)
      per patient and decreased to 0.4 (SD = 0.6, p < 0.05). Twenty-two of the 241
      initial drug changes (9%) were deprescribed during follow-up. Registered reasons
      for continuing PIDs are clinical or patients' preferences. Conclusions Performing
      medication reviews in polypharmacy patients seems useful to continue at least in
      high-risk patients in The Netherlands. The time-consuming reviews could be
      limited to patients who are willing to change their medication.

PMID- 29453679
TI  - The impact of timing of immunotherapy with cranial irradiation in melanoma
      patients with brain metastases: intracranial progression, survival and toxicity.
AB  - Immunotherapy (IT) is increasingly incorporated in the management of metastatic
      melanoma patients with brain metastases, but the impact of timing of IT with
      stereotactic radiosurgery (SRS) remains unclear. The aim of this study was to
      determine the temporal significance of IT in melanoma patients treated with
      cranial radiation therapy (RT) with respect to patterns of intracranial
      progression, overall survival (OS), and toxicity. We retrospectively reviewed
      consecutive melanoma patients with brain metastases undergoing cranial RT and IT
      between 2008 and 2015. Concurrent IT/RT was defined as IT administration within
      30 days of RT. Intracranial progression, OS and radionecrosis were assessed. We
      identified 74 patients with 136 treated brain metastases. Median OS was 13.9
      months. Performance status, pre-SRS surgery, and intracranial progression were
      correlated with OS. Concurrent IT/RT was used in 35 (47.3%) patients. Patients
      receiving concurrent IT/RT were less likely to have a BRAF mutation (p = 0.027)
      and more likely to be treated after 2013 (p = 0.010) compared to non-concurrently
      treated patients. Patients receiving concurrent IT/RT were more likely to have
      intracranial progression within 60-days (54.3% vs. 30.8%, p = 0.041). However,
      25.7% of concurrent IT/RT patients attained >= 1 year intracranial progression
      free survival. There were no significant differences in symptomatic radionecrosis
      (11.4% vs. 12.8%, p = 0.67). In conclusion, although melanoma patients with brain
      metastases receiving concurrent IT/RT were more likely to exhibit early
      intracranial disease progression, a significant proportion of non-early
      progressors attained durable intracranial control. The combination of IT and
      cranial RT appears to be efficacious and safe. Prospective studies are required
      to clarify these retrospective findings.

PMID- 29453678
TI  - Differential expression of the TWEAK receptor Fn14 in IDH1 wild-type and mutant
      gliomas.
AB  - The TNF receptor superfamily member Fn14 is overexpressed by many solid tumor
      types, including glioblastoma (GBM), the most common and lethal form of adult
      brain cancer. GBM is notable for a highly infiltrative growth pattern and several
      groups have reported that high Fn14 expression levels can increase tumor cell
      invasiveness. We reported previously that the mesenchymal and proneural GBM
      transcriptomic subtypes expressed the highest and lowest levels of Fn14 mRNA,
      respectively. Given the recent histopathological re-classification of human
      gliomas by the World Health Organization based on isocitrate dehydrogenase 1
      (IDH1) gene mutation status, we extended this work by comparing Fn14 gene
      expression in IDH1 wild-type (WT) and mutant (R132H) gliomas and in cell lines
      engineered to overexpress the IDH1 R132H enzyme. We found that both low-grade and
      high-grade (i.e., GBM) IDH1 R132H gliomas exhibit low Fn14 mRNA and protein
      levels compared to IDH1 WT gliomas. Forced overexpression of the IDH1 R132H
      protein in glioma cells reduced Fn14 expression, while treatment of IDH1 R132H
      overexpressing cells with the IDH1 R132H inhibitor AGI-5198 or the DNA
      demethylating agent 5-aza-2'-deoxycytidine increased Fn14 expression. These
      results support a role for Fn14 in the more aggressive and invasive phenotype
      associated with IDH1 WT tumors and indicate that the low levels of Fn14 gene
      expression noted in IDH1 R132H mutant gliomas may be due to epigenetic regulation
      via changes in DNA methylation.

PMID- 29453680
TI  - Prognostic implications of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET/CT
      in patients with glioma.
AB  - OBJECTIVE: The potential of positron emission tomography/computed tomography
      using 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) (62Cu-ATSM PET/CT), which
      was originally developed as a hypoxic tracer, to predict therapeutic resistance
      and prognosis has been reported in various cancers. Our purpose was to
      investigate prognostic value of 62Cu-ATSM PET/CT in patients with glioma,
      compared to PET/CT using 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). METHOD: 56
      patients with glioma of World Health Organization grade 2-4 were enrolled. All
      participants had undergone both 62Cu-ATSM PET/CT and 18F-FDG PET/CT within mean
      33.5 days prior to treatment. Maximum standardized uptake value and
      tumor/background ratio were calculated within areas of increased radiotracer
      uptake. The prognostic significance for progression-free survival and overall
      survival were assessed by log-rank test and Cox's proportional hazards model.
      RESULTS: Disease progression and death were confirmed in 37 and 27 patients in
      follow-up periods, respectively. In univariate analysis, there was significant
      difference of both progression-free survival and overall survival in age, tumor
      grade, history of chemoradiotherapy, maximum standardized uptake value and
      tumor/background ratio calculated using 62Cu-ATSM PET/CT. Multivariate analysis
      revealed that maximum standardized uptake value calculated using 62Cu-ATSM PET/CT
      was an independent predictor of both progression-free survival and overall
      survival (p < 0.05). In a subgroup analysis including patients of grade 4 glioma,
      only the maximum standardized uptake values calculated using 62Cu-ATSM PET/CT
      showed significant difference of progression-free survival (p < 0.05).
      CONCLUSIONS: 62Cu-ATSM PET/CT is a more promising imaging method to predict
      prognosis of patients with glioma compared to 18F-FDG PET/CT.

PMID- 29453681
TI  - 18F-FPYBF-2, a new F-18 labelled amyloid imaging PET tracer: biodistribution and
      radiation dosimetry assessment of first-in-man 18F-FPYBF-2 PET imaging.
AB  - OBJECTIVE: Recently, a benzofuran derivative for the imaging of beta-amyloid
      plaques, 5-(5-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)- N
      methylpyridin-2-amine (18F-FPYBF-2) has been validated as a tracer for amyloid
      imaging and it was found that 18F-FPYBF-2 PET/CT is a useful and reliable
      diagnostic tool for the evaluation of AD (Higashi et al. Ann Nucl Med,
      https://doi.org/10.1007/s12149-018-1236-1 , 2018). The aim of this study was to
      assess the biodistribution and radiation dosimetry of diagnostic dosages of 18F
      FPYBF-2 in normal healthy volunteers as a first-in-man study. METHODS: Four
      normal healthy volunteers (male: 3, female: 1; mean age: 40 +/- 17; age range 25
      56) were included and underwent 18F-FPYBF-2 PET/CT study for the evaluation of
      radiation exposure and pharmacokinetics. A 10-min dynamic PET/CT scan of the body
      (chest and abdomen) was performed at 0-10 min and a 15-min whole-body static scan
      was performed six times after the injection of 18F-FPYBF-2. After reconstructing
      PET and CT image data, individual organ time-activity curves were estimated by
      fitting volume of interest data from the dynamic scan and whole-body scans. The
      OLINDA/EXM version 2.0 software was used to determine the whole-body effective
      doses. RESULTS: Dynamic PET imaging demonstrated that the hepatobiliary and renal
      systems were the principal pathways of clearance of 18F-FPYBF-2. High uptake in
      the liver and the gall bladder, the stomach, and the kidneys were demonstrated,
      followed by the intestines and the urinary bladder. The ED for the adult
      dosimetric model was estimated to be 8.48 +/- 1.25 uSv/MBq. The higher absorbed
      doses were estimated for the liver (28.98 +/- 12.49 and 36.21 +/- 15.64 uGy/MBq),
      the brain (20.93 +/- 4.56 and 23.05 +/- 5.03u Gy/MBq), the osteogenic cells (9.67
      +/- 1.67 and 10.29 +/- 1.70 uGy/MBq), the small intestines (9.12 +/- 2.61 and
      11.12 +/- 3.15 uGy/MBq), and the kidneys (7.81 +/- 2.62 and 8.71 +/- 2.90
      uGy/MBq) for male and female, respectively. CONCLUSIONS: The ED for the adult
      dosimetric model was similar to those of other agents used for amyloid PET
      imaging. The diagnostic dosage of 185-370 MBq of 18F-FPYBF-2 was considered to be
      acceptable for administration in patients as a diagnostic tool for the evaluation
      of AD.

PMID- 29453682
TI  - Persistent Pulmonary Hypertension and Histologic Chorioamnionitis in Preterm
      Infants: Controlled Study.
AB  - Persistent pulmonary hypertension (PPHN) of the newborn is one of the most
      challenging acute disorders of postnatal transition with substantial morbidity
      and mortality. The aim of the study was to find if there is an association
      between persistent pulmonary hypertension and histologic chorioamnionitis in
      preterm infants. 27 preterm infants with echocardiographic evidence of PPHN
      within the first 3 days of life were eligible for the study. A matched control
      group of 27 patients was chosen according to gestational age, date of birth, and
      gender. Data collection included the need for respiratory support, use of nitric
      oxide oxygen supplementation, duration of rupture of membranes, blood culture,
      blood count, and C-reactive protein levels at birth and 12 h. Maternal clinical
      and laboratory data suggesting clinical chorioamnionitis Placentas of both groups
      were examined. Differences between groups were analyzed using two-tail t test,
      Kolmogorov-Smirnov test, Chi-square test. No statistically differences were found
      in all parameters compared between groups, except for a higher number of patients
      in the PPHN group who were treated by oxygen supplementation. An association was
      not found between the incidence of HCA and echocardiographic PPHN in preterm
      infants in the first 3 days of life.

PMID- 29453683
TI  - Flow Energy Loss as a Predictive Parameter for Right Ventricular Deterioration
      Caused by Pulmonary Regurgitation After Tetralogy of Fallot Repair.
AB  - The optimal timing for pulmonary valve replacement after Tetralogy of Fallot
      (TOF) repair remains controversial. In this study, we estimated the feasibility
      of using flow energy loss (FEL) to predict right ventricular (RV) deterioration
      due to pulmonary regurgitation after TOF repair. We examined RV outflow tract
      (RVOT) flow in nine patients who underwent TOF or double-outlet right ventricle
      repair in the intervention group (Group I) and compared them with three healthy
      children in the control group (Group C). We evaluated flow across the RVOT and
      pulmonary valve by vector flow mapping (VFM) on echocardiography and by phase
      contrast-magnetic resonance imaging (PC-MRI). Next, we calculated FEL and
      analyzed the relationship between FEL and clinical parameters of RV function. The
      mean FEL was significantly greater in Group I than in Group C (p = 0.002). Flow
      pattern and FEL were comparable by VFM and PC-MRI at the same phase 14.6 years
      after TOF repair. There was a significant positive correlation for the
      cardiothoracic ratio with both the mean FEL [correlation coefficient (r) = 0.78;
      p = 0.012] and the diastolic peak FEL (r = 0.75; p = 0.021) in Group I. There was
      also a significant positive correlation between the serial change in QRS duration
      with both the mean FEL (r = 0.82; p = 0.014) and the diastolic FEL (r = 0.70; p =
      0.052) in Group I. FEL by VFM is an effective tool for evaluating ventricular
      deterioration caused by RV workload.

PMID- 29453685
TI  - Transcatheter Closure of Arterial Duct in Infants < 6 kg: Amplatzer Duct Occluder
      Type I vs Amplatzer Duct Occluder II Additional Sizes.
AB  - Transcatheter closure of arterial duct (AD) remains challenging in low-weight
      patients and using Amplatzer Duct Occluder devices is still considered off-label
      in infants < 6 kg. This study aimed to report a large, single-center experience
      of percutaneous AD closure in infants < 6 kg as well as to compare the most
      frequently used devices, Amplatzer Duct Occluder type I (ADO I) and Amplatzer
      Duct Occluder type II Additional Sizes devices (ADO II-AS) (St. Jude Medical
      Corp, St. Paul, MN, USA). From March 2000 to March 2017, among the 762 patients
      submitted to percutaneous closure of AD at our Institution, 33 were infants < 6
      kg (age 4.8 +/- 2.1 months; weight 5.0 +/- 0.9 kg). Fourteen patients (45%)
      underwent ADO I (Group I) and 19 patients ADO II-AS (Group II) device
      implantation. AD diameter was 2.6 +/- 0.8 (range 1.5-4.0) mm resulting in QP/QS
      of 2.6 +/- 0.0.9 (range 1.1-4.5). Successful device deployment was achieved in
      all patients without procedural morbidity or mortality. Procedural and
      fluoroscopy times were not significantly different between the groups. However,
      total X-ray absorbed dose was significantly higher in Group I (121 +/- 69 vs 29
      +/- 16 mGy/cm2, p < 0.01). Immediate, 24 h, and mid-term (46 +/- 37 months,
      median 39) complete occlusion were recorded in 72.7, 90.9, and 97% of patients,
      respectively without significant difference between the groups. In conclusion,
      transcatheter closure of AD with Amplatzer Duct Occluder devices is feasible,
      safe, and effective also in infants less than 6 kg, without significant
      difference between the most commonly used devices, namely, ADO I and ADO II-AS.

PMID- 29453686
TI  - Antipsychotic Prescribing and Safety Monitoring Practices in Children and Youth:
      A Population-Based Study in Alberta, Canada.
AB  - BACKGROUND AND OBJECTIVE: Antipsychotic medication use has steadily increased in
      Canada, with an expansion in the profile of users and the diagnoses for which
      they are used. The use of antipsychotics is associated with a number of adverse
      effects for which routine monitoring is recommended. The objectives of this study
      were to determine the most common diagnoses associated with antipsychotic use in
      children in Alberta, Canada and the proportion who receive recommended laboratory
      tests for adverse effects. METHODS: Data on dispensed antipsychotics, diagnoses,
      prescribers, and laboratory testing were obtained from provincial data sources.
      To assess the frequency of metabolic and hormonal laboratory baseline and/or
      follow-up testing, the sample was divided into an antipsychotic-naive cohort and
      an antipsychotic non-naive cohort. RESULTS: In 2014, 6916 children were dispensed
      at least one second- or third-generation antipsychotic. The most frequently
      dispensed antipsychotics were risperidone (3908 children), quetiapine (2140
      children), and aripiprazole (1302 children). The majority of children prescribed
      risperidone were diagnosed with Attention Deficit Hyperactivity Disorder (ADHD)
      or conduct disorder. Quetiapine was mainly prescribed for neurotic disorder or
      depression, while aripiprazole was prescribed most frequently for conduct
      disorder or neurotic disorders. Among antipsychotic-naive patients, 17% had at
      least one laboratory test done at baseline, and 35% had at least one laboratory
      test done at follow-up. In the non-naive patients, 42% had at least one follow-up
      laboratory test. Lipid and glucose testing were done in less than 5% of the naive
      cohort at baseline, and in less than 15% at follow-up. In the non-naive cohort,
      less than 22% received lipid or glucose testing during the year 2014.
      CONCLUSIONS: The majority of antipsychotic use in children in Alberta is off
      label and associated with disruptive behavior disorders, depression, and anxiety
      disorders. The vast majority of children prescribed antipsychotic medications do
      not undergo recommended laboratory tests.

PMID- 29453687
TI  - Impact of Boosted Antiretroviral Therapy on the Pharmacokinetics and Efficacy of
      Clopidogrel and Prasugrel Active Metabolites.
AB  - BACKGROUND AND OBJECTIVES: Prasugrel and clopidogrel are inhibitors of the ADP
      P2Y12 platelet receptor used in acute coronary syndrome patients. They require
      bioactivation via isoenzymes such as cytochrome P450 (CYP) 3A4, CYP2C19 and
      CYP2B6. Ritonavir and cobicistat are potent CYP3A inhibitors, prescribed as
      pharmacokinetic (PK) enhancers in the treatment of human immunodeficiency virus
      (HIV) infection. METHODS: In this study, the impact of boosted antiretroviral
      therapies (ARTs) on the PK of clopidogrel and prasugrel active metabolites (AMs),
      and on the efficacy of prasugrel and clopidogrel, were evaluated in a randomized
      crossover clinical trial. RESULTS: A significantly lower exposure to clopidogrel
      AM [3.2-fold lower area under the concentration-time curve (AUC) and maximum
      plasma concentration (Cmax)] and prasugrel AM (2.1-fold and 1.7-fold lower AUC
      and Cmax) were demonstrated in HIV-infected patients treated with boosted ARTs
      compared with healthy controls; however, a differential impact was observed on
      platelet inhibition between clopidogrel and prasugrel. Clopidogrel 300 mg induced
      adequate (although modest) platelet inhibition in all healthy subjects, while
      platelet inhibition was insufficient in 44% of HIV patients. On the contrary,
      prasugrel 60 mg induced a potent platelet inhibition in both healthy and HIV
      infected subjects. CONCLUSION: Prasugrel appears to remain an adequate
      antiplatelet agent in HIV-infected patients and could be preferred to clopidogrel
      in this context, regardless of the metabolic interaction and inhibition of its
      bioactivation pathways.

PMID- 29453688
TI  - Rapid optimization of spore production from Bacillus amyloliquefaciens in
      submerged cultures based on dipicolinic acid fluorimetry assay.
AB  - Some optimization techniques have been widely applied for spore fermentation
      based on the plate counting. This study optimized the culture medium for the
      spore production of Bacillus amyloliquefaciens BS-20 and investigated the
      feasibility of using a dipicolonic acid (DPA) fluorimetry assay as a simpler
      alternative to plate counting for evaluating spore yields. Through the single
      factor experiment, the metal ions and agro-industrial raw materials that
      significantly enhanced spore production were determined. After conducting a
      response surface methodology (RSM) analysis of several metal ions, the combined
      use of optimum concentrations of Mn2+, Fe2+, and Ca2+ in culture media produced a
      3.4-fold increase in spore yields. Subsequently, supplementing soybean meal and
      corn meal with optimum concentrations determined by another RSM analysis produced
      an 8.8-fold increase. The final spore concentration from a culture medium
      incorporating optimum concentrations of the metal ions and raw materials
      mentioned above was verified to reach (8.05 +/- 0.70) * 109 CFU/mL by both DPA
      fluorimetry and plate counting. The results suggest that the use of DPA
      fluorescence intensity as an alternative value to colony counting provides a
      general method for assessing spore yields with less work and shorter time.

PMID- 29453689
TI  - Sustained sensorimotor control as intermittent decisions about prediction errors:
      computational framework and application to ground vehicle steering.
AB  - A conceptual and computational framework is proposed for modelling of human
      sensorimotor control and is exemplified for the sensorimotor task of steering a
      car. The framework emphasises control intermittency and extends on existing
      models by suggesting that the nervous system implements intermittent control
      using a combination of (1) motor primitives, (2) prediction of sensory outcomes
      of motor actions, and (3) evidence accumulation of prediction errors. It is shown
      that approximate but useful sensory predictions in the intermittent control
      context can be constructed without detailed forward models, as a superposition of
      simple prediction primitives, resembling neurobiologically observed corollary
      discharges. The proposed mathematical framework allows straightforward extension
      to intermittent behaviour from existing one-dimensional continuous models in the
      linear control and ecological psychology traditions. Empirical data from a
      driving simulator are used in model-fitting analyses to test some of the
      framework's main theoretical predictions: it is shown that human steering
      control, in routine lane-keeping and in a demanding near-limit task, is better
      described as a sequence of discrete stepwise control adjustments, than as
      continuous control. Results on the possible roles of sensory prediction in
      control adjustment amplitudes, and of evidence accumulation mechanisms in control
      onset timing, show trends that match the theoretical predictions; these warrant
      further investigation. The results for the accumulation-based model align with
      other recent literature, in a possibly converging case against the type of
      threshold mechanisms that are often assumed in existing models of intermittent
      control.

PMID- 29453690
TI  - The effectiveness of targeted relative to empiric prophylaxis on infectious
      complications after transrectal ultrasound-guided prostate biopsy: a meta
      analysis.
AB  - PURPOSE: Rectal culture screening for fluoroquinolone (FQ)-resistant
      Enterobacteriaceae before transrectal ultrasound guided prostate (TRUSPB) biopsy
      and targeted antibiotic prophylaxis (TAP) may decrease post-TRUSPB infection
      rates compared to empiric (EAP) regimens. The objective of this study was to
      evaluate the effectiveness of targeted relative to empiric prophylaxis regimens
      on rates of infectious complications after TRUSPB and to determine the baseline
      prevalence of FQ resistance based on prior rectal swabs. METHODS: An electronic
      search within literature databases including EMBASE and Web of Science (all
      databases) for articles assessing TAP as an approach to TRUSPB prophylaxis was
      conducted. Quality assessment was performed using the Hoy instrument. Meta
      analysis was performed using MetaXL 5.3. RESULTS: From 15 studies (eight
      retrospective and seven prospective) representing 12,320 participants, infectious
      complication incidence was 3.4% in EAP and 0.8% in TAP patients. The number
      needed to treat with TAP to avoid one more infection when compared to the EAP
      group was 39. Effect sizes were homogeneous. Prevalence of FQ resistance showed
      low (15%) and high (28%) subgroups, likely due to region of origin (within and
      outside USA, respectively). CONCLUSIONS: Rectal culture prior to TRUSPB and use
      of TAP adjusts for endemic FQ resistance and is associated with less infectious
      complications and resulting morbidity when compared to EAP. Overtreatment
      associated with augmented prophylaxis approaches may be reduced as a result.
      Further prospective assessment and cost-benefit analyses are required before
      widespread implementation can be recommended.

PMID- 29453691
TI  - Effect of phosphorylation and single nucleotide polymorphisms on caspase
      substrates processing.
AB  - Posttranslational modifications that involve either reversible covalent
      modification of proteins or irreversible proteolysis are central to the
      regulation of key cellular mechanisms, including apoptosis, cell-cycle regulation
      and signal transduction. There is mounting evidence suggesting cross-talk between
      proteases and kinases. For instance: caspases, a class of proteases involved in
      programmed cell death-apoptosis, cleave a large set of various types of proteins.
      Simultaneously, kinases restrict caspase activity by phosphorylating their
      protein substrates in the vicinity of cleavage site. In addition, the caspase
      cleavage pattern in target proteins may be modified as a result of single
      nucleotide polymorphisms (SNPs) in the coding gene. This may either create a
      novel cleavage site, or increase/decrease the cleavage efficiency of a substrate.
      Such point mutations are often associated with the onset of disease. In this
      study, we predicted how phosphorylation and SNPs affect known human caspase
      proteolytic events collected in the CASBAH and Degrabase databases by applying
      Random Forest caspases' substrates prediction method, as implemented in the
      CaspDB, and the molecular dynamics free energy simulations approach. Our analysis
      confirms several experimental observations. Phosphorylation could have both
      positive or negative regulatory effects depending on its position with respect to
      the caspase cleavage site. For instance, we demonstrate that phosphorylation at
      P1' is the most detrimental for proteolytic efficiency of caspases.
      Phosphorylation at the P2 and P2' positions also negatively affect the cleavage
      events. In addition, we uncovered SNPs in 11 caspase substrates capable of
      completely abolishing the cleavage site due to polymorphism at the P1 position.
      The findings presented here may be useful for determining the link between
      aberrant proteolysis and disease.

PMID- 29453692
TI  - Unacylated ghrelin and obestatin in pediatric CKD: are they important in protein
      energy wasting?

PMID- 29453693
TI  - Exploiting the unique phenotypes of the earthworm Eudrilus eugeniae to evaluate
      the toxicity of chemical substances.
AB  - Both the evaluation and the determination of toxicity of chemical substances
      present in the environment have implications in human health. In this present
      study, the natural phenomenon named autotomy, a self-defense mechanism employed
      by several animals against the toxic chemical contaminants, was considered to
      assess the toxicity of different chemical substances. We investigated the effects
      of glucose, sodium chloride, kanamycin, mercuric chloride, arsenic trioxide, and
      lead oxide on the phenotypes of earthworm Eudrilus eugeniae. Depending on the
      concentration of different chemicals, worms exhibit unique phenotypes. These
      phenotypes can be used to identify the toxicity as well as the toxic
      concentration of the chemicals. Upon exposure to toxic chemicals, worms use
      different mechanical forces at the site of cleavage furrow to detach its
      segments. During the detachment, there is no apparent blood loss at both the ends
      of the worm. Our results show that the mercuric chloride is toxic at the
      concentration above 5 MUg when compared to other chemicals. Based on our
      findings, the toxic effects of a chemical and the toxic concentration of a
      chemical can be evaluated in both cost and time-efficient manner; in addition,
      these chemicals can be classified into the following categories: (1) mercuric
      chloride is extreme-toxic, (2) arsenic trioxide and lead oxide is toxic, (3)
      kanamycin and sodium chloride is low-toxic, and (4) glucose is non-toxic.

PMID- 29453694
TI  - Percutaneous left atrial appendage occlusion in the prevention of stroke in
      atrial fibrillation: a systematic review.
AB  - Atrial fibrillation is commonly coexistent with heart failure, and the management
      of the heart failure patient would be incomplete without an appreciation for
      atrial fibrillation management. There are many complications associated with oral
      anticoagulation in the prevention of stroke related to atrial fibrillation. In
      recent years, the advent of several percutaneous left atrial appendage (LAA)
      occlusion/closure strategies has sought to provide an alternative treatment
      modality. Here, we systematically review the published literature to investigate
      the efficacy and safety of percutaneous LAA occlusion/closure devices. We
      searched PubMed, EMBASE, Cochrane database of systematic reviews, and the FDA
      Medical Devices database. Using prespecified criteria, we identified studies of
      the Amplatzer Cardiac Plug (St. Jude Medical), Amplatzer Amulet (St. Jude
      Medical), Lariat suture delivery device (SentreHeart), and Watchman device
      (Boston Scientific). We analyzed 2 randomized controlled trials (RCT) and 15 non
      randomized registries that satisfied the study criteria. The two RCT both studied
      the Watchman device versus standard warfarin therapy; the studies indicate that
      the Watchman may be non-inferior to warfarin. Long-term efficacy outcomes for the
      Watchman device are promising. Data regarding the Amplatzer Cardiac Plug,
      Amplatzer Amulet, and Lariat suture delivery device are limited by the paucity of
      RCT data. High-quality prospective research is needed to directly compare LAA
      occlusion/closure strategies against one another as well as versus the direct
      oral anticoagulation medications. Data regarding the role of LAA occlusion in the
      heart failure population are lacking.

PMID- 29453695
TI  - Temporary assist device support for the right ventricle: pre-implant and post
      implant challenges.
AB  - Severe right ventricular (RV) failure is more likely reversible than similar
      magnitudes of left ventricular (LV) failure and, because reversal of both
      adaptive remodeling and impaired contractility require most often only short
      periods of support, the use of temporary RV assist devices (t-RVADs) can be a
      life-saving therapy option for many patients. Although increased experience with
      t-RVADs and progresses made in the development of safer devices with lower risk
      for complications has improved both recovery rate of RV function and patient
      survival, the mortality of t-RVAD recipients can still be high but it depends
      mainly on the primary cause of RV failure (RVF), the severity of end-organ
      dysfunction, and the timing of RVAD implantation, and much less on adverse events
      and complications related to RVAD implantation, support, or removal. Reduced
      survival of RVAD recipients should therefore not discourage appropriate
      application of RVADs because their underuse further reduces the chances for RV
      recovery and patient survival. The article reviews and discusses the challenges
      related to the pre-implant and post-implant decision-making processes aiming to
      get best possible therapeutic results. Special attention is focused on pre
      implant RV assessment and prediction of RV improvement during mechanical
      unloading, patient selection for t-RVAD therapy, assessment of unloading-promoted
      RV recovery, and prediction of its stability after RVAD removal. Particular
      consideration is also given to prediction of RVF after LVAD implantation which is
      usually hampered by the complex interactions between the different risk factors
      related indirectly or directly to the RV potential for reverse remodeling and
      functional recovery.

PMID- 29453697
TI  - The sacral autonomic outflow is parasympathetic: Langley got it right.
AB  - A recent developmental study of gene expression by Espinosa-Medina, Brunet and
      colleagues sparked controversy by asserting a revised nomenclature for divisions
      of the autonomic motor system. Should we re-classify the sacral autonomic outflow
      as sympathetic, as now suggested, or does it rightly belong to the
      parasympathetic system, as defined by Langley nearly 100 years ago? Arguments for
      rejecting Espinosa-Medina, Brunet et al.'s scheme subsequently appeared in e
      letters and brief reviews. A more recent commentary in this journal by Brunet and
      colleagues responded to these criticisms by labeling Langley's scheme as a
      historical myth perpetuated by ignorance. In reaction to this heated exchange, I
      now examine both sides to the controversy, together with purported errors by the
      pioneers in the field. I then explain, once more, why the sacral outflow should
      remain known as parasympathetic, and outline suggestions for future
      experimentation to advance the understanding of cellular identity in the
      autonomic motor system.

PMID- 29453699
TI  - Unusual Intestinal Involvement by Paracoccidioidomycosis Diagnosed After Oral
      Manifestation.
AB  - Paracoccidioidomycosis is a common deep fungus infection in South America,
      particularly in Brazil. It is acquired through inhalation and primary involvement
      of lungs. Subsequently, dissemination may occur and oral mucosa is frequently
      affected and actually, in most of the cases the diagnosis is established because
      of the oral lesions. Thus, the role of the dentist is fundamental to correct
      diagnosis. However, the involvement of intestine is rarely reported. The current
      case describes a 36-year-old man who presented abdominal pain and intestinal
      constipation, being suspected and then confirmed as paracoccidioidomycosis after
      already be diagnosed with this disease by a dentist through oral manifestations.

PMID- 29453698
TI  - Corneal Collagen Cross-Linking for the Management of Mycotic Keratitis.
AB  - PURPOSE: To evaluate the efficiency of corneal collagen cross-linking (CXL) in
      addition to topical voriconazole in cases with mycotic keratitis. DESIGN:
      Retrospective case series in a tertiary university hospital. PARTICIPANTS: CXL
      was performed on 13 patients with mycotic keratitis who presented poor or no
      response to topical voriconazole treatment. METHODS: The clinical features,
      symptoms, treatment results and complications were recorded retrospectively. The
      corneal infection was graded according to the depth of infection into the stroma
      (from grade 1 to grade 3). The visual analogue scale was used to calculate the
      pain score before and 2 days after surgery. MAIN OUTCOME MEASURES: Grade of the
      corneal infection. RESULTS: Mean age of 13 patients (6 female and 7 male) was
      42.4 +/- 17.7 years (20-74 years). Fungus was demonstrated in culture (eight
      patients) or cytological examination (five patients). Seven of the 13 patients
      (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 +/-
      10 days (15-40 days). The remaining six patients did not respond to CXL
      treatment; they initially presented with higher grade ulcers. Pre- and post
      operative pain score values were 8 +/- 0.8 and 3.5 +/- 1, respectively (p <
      0.05). CONCLUSIONS: The current study suggests that adjunctive CXL treatment is
      effective in patients with small and superficial mycotic ulcers. These
      observations require further research by large randomized clinical trials.

PMID- 29453700
TI  - Reliability of cartilage digestion and FDA-EB fluorescence staining for the
      detection of chondrocyte viability in osteochondral grafts.
AB  - The purpose of this study is to evaluate the reliability of cartilage digestion
      and fluorescein diacetate-ethidium bromide (FDA-EB) fluorescence staining for the
      detection of chondrocyte viability in osteochondral grafts. Sixteen fresh
      osteochondral grafts were harvested from pig knee condyles, and the articular
      cartilage tissue was preserved. Each cartilage graft was cut into two 70-um thick
      pieces and randomly allocated to Group A or Group B. The cell viability of Group
      A was detected using FDA-EB fluorescence staining of the digested cartilage, and
      the viability of Group B was detected with FDA-EB fluorescence staining of
      cartilage sections. Comparisons of chondrocyte viability and correlation analyses
      of the two groups were performed using the paired sample t test and Pearson
      correlation test, respectively. No significant difference was found in the
      chondrocyte viability between Groups A and B (p > 0.05), and a strong correlation
      was observed (r = 0.70, p < 0.05). Therefore, cartilage digestion with FDA-EB
      fluorescence staining is a reliable method for detecting chondrocyte viability in
      osteochondral grafts.

PMID- 29453696
TI  - Interrelationship between diabetes mellitus and heart failure: the role of
      peroxisome proliferator-activated receptors in left ventricle performance.
AB  - Heart failure (HF) is a common cardiac syndrome, whose pathophysiology involves
      complex mechanisms, some of which remain unknown. Diabetes mellitus (DM)
      constitutes not only a glucose metabolic disorder accompanied by insulin
      resistance but also a risk factor for cardiovascular disease and HF. During the
      last years though emerging data set up, a bidirectional interrelationship between
      these two entities. In the case of DM impaired calcium homeostasis, free fatty
      acid metabolism, redox state, and advance glycation end products may accelerate
      cardiac dysfunction. On the other hand, when HF exists, hypoperfusion of the
      liver and pancreas, b-blocker and diuretic treatment, and autonomic nervous
      system dysfunction may cause impairment of glucose metabolism. These molecular
      pathways may be used as therapeutic targets for novel antidiabetic agents.
      Peroxisome proliferator-activated receptors (PPARs) not only improve insulin
      resistance and glucose and lipid metabolism but also manifest a diversity of
      actions directly or indirectly associated with systolic or diastolic performance
      of left ventricle and symptoms of HF. Interestingly, they may beneficially affect
      remodeling of the left ventricle, fibrosis, and diastolic performance but they
      may cause impaired water handing, sodium retention, and decompensation of HF
      which should be taken into consideration in the management of patients with DM.
      In this review article, we present the pathophysiological data linking HF with DM
      and we focus on the molecular mechanisms of PPARs agonists in left ventricle
      systolic and diastolic performance providing useful insights in the molecular
      mechanism of this class of metabolically active regiments.

PMID- 29453701
TI  - EANM guidelines for radionuclide therapy of bone metastases with beta-emitting
      radionuclides.
AB  - The skeleton is the most common metastatic site in patients with advanced cancer.
      Pain is a major healthcare problem in patients with bone metastases. Bone-seeking
      radionuclides that selectively accumulate in the bone are used to treat cancer
      induced bone pain and to prolong survival in selected groups of cancer patients.
      The goals of these guidelines are to assist nuclear medicine practitioners in:
      (a) evaluating patients who might be candidates for radionuclide treatment of
      bone metastases using beta-emitting radionuclides such as strontium-89 (89Sr),
      samarium-153 (153Sm) lexidronam (153Sm-EDTMP), and phosphorus-32 (32P) sodium
      phosphate; (b) performing the treatments; and

PMID- 29453703
TI  - Reply: Interim FDG-PET/CT in primary mediastinal diffuse large B-cell lymphoma:
      really almost useless procedure?

PMID- 29453704
TI  - Brief Report: Reliability of the Participation and Sensory Environment
      Questionnaire: Home Scales.
AB  - The Participation and Sensory Environment Questionnaire: Home Scales (P-SEQ):
      Home Scales is a parent report tool designed to assess the impact of the sensory
      environment on participation in daily activities in the home of children with and
      without autism spectrum disorder. A cross-sectional study was completed to
      determine internal consistency, test-retest reliability, and examine item
      distribution. A total of 304 parents of children between the ages of 2 and 7
      years of age completed the P-SEQ: Home Scales. Results identified excellent
      internal consistency (alpha = 0.96), moderate test-retest reliability (r = .62),
      and reasonable item distribution. Results suggest that the P-SEQ: Home Scales
      provides reliable estimates of the impact of the sensory environment on
      children's participation in home activities.

PMID- 29453702
TI  - The relationship between local recurrences and distant metastases in prostate
      cancer: can 11C-choline PET/CT contribute to understand the link?
AB  - PURPOSE: Previous studies in prostate cancer (PCa) patients tried to correlate
      the onset of local recurrence (LR) with the development of distant metastases and
      formulated, based on theoretical and experimental data, hypotheses linking the
      two events. We aimed to address this issue with 11C-choline positron emission
      tomography/computed tomography (PET/CT). METHODS: This retrospective study
      included 491 PCa patients previously treated with radical prostatectomy who had
      undergone 11C-choline PET/CT owing to biochemical failure. Further inclusion
      criteria were availability of clinical and pathological variables for survival
      analysis. Statistical significance was taken at P < 0.05. RESULTS: Seventy-two
      patients (14.7%) had evidence of LR at 11C-choline PET/CT. The frequency of LR
      increased from 13.8% in the interval 0-4 years after prostatectomy, to 23.9% in
      the 12-16-year interval (P = 0.080). On the contrary, the frequency of lymph node
      metastases (overall rate in the 0-16 years interval after prostatectomy: 26.3%)
      and of bone metastases (overall rate: 13.8%) decreased significantly over time.
      Kaplan-Meier curves showed no significant group difference in the rates of lymph
      node or bone metastases between patients with LR and patients without LR. LR
      significantly predicted PCa-specific survival at univariate analysis, but the
      statistical significance was lost at multivariate analysis. CONCLUSION: We found
      no differences in the rates of lymph node and bone metastases between patients
      with and without LR. An inverse time-dependent trend was observed in the
      frequency of LR on one side and of lymph node and bone metastases on the other
      side. These findings were discussed in relation to previous theories linking LR
      to distant metastases and our study design.

PMID- 29453705
TI  - Using Peer-Mediated LEGO(r) Play Intervention to Improve Social Interactions for
      Chinese Children with Autism in an Inclusive Setting.
AB  - The purpose of this study was to examine the effects of a peer-mediated LEGO(r)
      play intervention on improving social skills for children with ASD in an
      inclusive preschool in China. Three boys with ASD and 13 typically developing
      children participated in this study. A multiple-probe across participants design
      was used. The intervention consisted of LEGO(r) construction activities
      incorporated with peer-mediated strategies for one child with ASD and two
      typically developing peers. The intervention sessions were conducted two sessions
      per week with a total of 28-31 sessions for each participant. Results indicated
      that all three children with ASD increased their social initiations and responses
      following the completion of the intervention. Social validity was also obtained.

PMID- 29453706
TI  - Family Experiences with the Diagnosis of Autism Spectrum Disorder: System
      Barriers and Facilitators of Efficient Diagnosis.
AB  - This paper examines family experiences with the efficiency of ASD diagnosis.
      Children were age 8 or younger with ASD (n = 450). Outcomes were delay from first
      parent concern to diagnosis, shifting diagnoses, and being told child did not
      have ASD. Predictors were screening, travel distance, and problems finding
      providers. Logit models were used to examine associations. Screening was
      associated with reduced delay in diagnosis; problems finding providers were
      associated with greater delay. Screening, travel distance, and delay in diagnosis
      were associated with shifting diagnoses and being told child did not have ASD.
      Physician and parent training in communication and addressing mental health
      professional shortages and maldistribution may improve the diagnosis experiences
      of families of children with ASD.

PMID- 29453708
TI  - Exploring the Effectiveness of a Peer-Mediated Model of the PEERS Curriculum: A
      Pilot Randomized Control Trial.
AB  - This study compared immediate and 4-month outcomes among adolescents with autism
      spectrum disorder randomly assigned to the PEERS curriculum (n = 10), a peer
      mediated PEERS curriculum (n = 12), or a delayed treatment control group (n =
      12). Findings suggest a modest advantage in social skills knowledge and social
      functioning for participants in the peer-mediated PEERS curriculum relative to
      Traditional PEERS, and gains in social skills knowledge, social functioning, and
      reductions in loneliness were maintained in one or both treatment groups at a 4
      month follow-up. Typically developing peer mentors (n = 16) showed improvements
      in social skills knowledge and marginal improvements in autism knowledge and
      loneliness. Future research with a larger sample and objective outcome measures
      is needed.

PMID- 29453707
TI  - Brief Report: When Large Becomes Slow: Zooming-Out Visual Attention Is Associated
      to Orienting Deficits in Autism.
AB  - Previous studies independently demonstrated impairments in rapid
      orienting/disengagement and zooming-out of spatial attention in autism spectrum
      disorder (ASD). These attentional mechanisms, however, are not completely
      independent. Aiming at a more complete picture of spatial attention deficits in
      ASD, we examined the relationship between orienting and zooming in participants
      with ASD and typically developing peers. We modified a classical spatial cuing
      task, presenting two small or large cues in the two visual hemifields and
      subsequently cueing attention to one of them. Our results demonstrate a sluggish
      orienting mechanism in ASD only when a large attentional focus is deployed.
      Moreover, only the sluggish orienting mechanism in the large cues condition
      predicts the severity in the social-interaction symptomatology in individuals
      with ASD.

PMID- 29453709
TI  - Prediction of Autism at 3 Years from Behavioural and Developmental Measures in
      High-Risk Infants: A Longitudinal Cross-Domain Classifier Analysis.
AB  - We integrated multiple behavioural and developmental measures from multiple time
      points using machine learning to improve early prediction of individual Autism
      Spectrum Disorder (ASD) outcome. We examined Mullen Scales of Early Learning,
      Vineland Adaptive Behavior Scales, and early ASD symptoms between 8 and 36 months
      in high-risk siblings (HR; n = 161) and low-risk controls (LR; n = 71).
      Longitudinally, LR and HR-Typical showed higher developmental level and
      functioning, and fewer ASD symptoms than HR-Atypical and HR-ASD. At 8 months,
      machine learning classified HR-ASD at chance level, and broader atypical
      development with 69.2% Area Under the Curve (AUC). At 14 months, ASD and broader
      atypical development were classified with approximately 71% AUC. Thus, prediction
      of ASD was only possible with moderate accuracy at 14 months.

PMID- 29453712
TI  - Author Correction to: Psoriasis in Skin of Color: Insights into the Epidemiology,
      Clinical Presentation, Genetics, Quality-of-Life Impact, and Treatment of
      Psoriasis in Non-White Racial/Ethnic Groups.
AB  - In the original publication, section 5, paragraph 1 was incorrectly published.

PMID- 29453711
TI  - Prevalence of DSM-5 Autism Spectrum Disorder Among School-Based Children Aged 3
      12 Years in Shanghai, China.
AB  - We estimated the prevalence of ASD in a population-based sample comprising
      children aged 3-12 years (N = 74,252) in Shanghai. This included a high-risk
      group sampled from special education schools and a low-risk group randomly
      sampled from general schools. First, we asked parents and then teachers to
      complete the Social Communication Questionnaire for participating children.
      Children who screened positive based on both parental and teachers' reports were
      comprehensively assessed. ASD was identified based on DSM-5 criteria. We
      identified 711 children as being at-risk for ASD, of which 203 were identified as
      ASD cases. The prevalence of ASD was 8.3 per 10,000, which is likely an
      underestimate, given that 81.6% of the children diagnosed with ASD had IQs below
      40. This is the first report on the prevalence of ASD according to DSM-5 in
      China.

PMID- 29453710
TI  - Investigating Mirror System (MS) Activity in Adults with ASD When Inferring
      Others' Intentions Using Both TMS and EEG.
AB  - ASD is associated with mentalizing deficits that may correspond with atypical
      mirror system (MS) activation. We investigated MS activity in adults with and
      without ASD when inferring others' intentions using TMS-induced motor evoked
      potentials (MEPs) and mu suppression measured by EEG. Autistic traits were
      measured for all participants. Our EEG data show, high levels of autistic traits
      predicted reduced right mu (8-10 Hz) suppression when mentalizing. Higher left mu
      (8-10 Hz) suppression was associated with superior mentalizing performances. Eye
      tracking and TMS data showed no differences associated with autistic traits. Our
      data suggest ASD is associated with reduced right MS activity when mentalizing,
      TMS-induced MEPs and mu suppression measure different aspects of MS functioning
      and the MS is directly involved in inferring intentions.

PMID- 29453713
TI  - 1H, 13C, and 15N resonance assignments of CW domain of the N-methyltransferase
      ASHH2 free and bound to the mono-, di- and tri-methylated histone H3 tail
      peptides.
AB  - The ASHH2 CW domain is responsible for recognizing the methylation state at
      lysine 4 of histone 3 N-terminal tails and implicated in the recruitment of the
      ASHH2 methyltransferase enzyme correctly to the histones. The ASHH2 CW domain
      binds H3 lysine motifs that can be either mono-, di-, or tri-methylated
      [ARTK(meX)QTAR, where X denotes the number of methylations], but binds strongest
      to monomethylated instances (Kd values reported in the range of 1 um to 500 nM).
      Hoppmann et al. published the uncomplexed NMR structure of an ASHH2 CW domain in
      2011. Here we document the assignment of a shortened ASHH2 CW construct, CW42,
      with similar binding affinity and better expression yields than the one used to
      solve the uncomplexed structure. We also perform 1H-15N HSQC-monitored titrations
      that document at which protein-peptide ratios the complex is saturated. Backbone
      resonance assignments are presented for this shortened ASHH2 CW domain alone and
      bound to an H3 histone tail mimicking peptide monomethylated on lysine 4
      (ARTK(me1)QTAR). Likewise, the assignment was also performed for the protein in
      complex with the dimethylated (ARTK(me2)QTAR) and trimethylated (ARTK(me3)QTAR)
      peptide. Overall, these two latter situations displayed a similar perturbation of
      shifts as the mono-methylated instance. In the case of the monomethylated histone
      tail mimic, side-chain assignment of CW42 in this complex was performed and
      reported in addition to backbone assignment, in preparation of a future solution
      structure determination and dynamics characterization of the CW42-ARTK(me1)QTAR
      complex.

PMID- 29453714
TI  - Backbone 1H, 13C, and 15N assignments of the extracellular region of human
      Fcgamma receptor IIIb.
AB  - Fcgamma receptor (FcgammaR) promotes various immune responses through
      interactions with the Fc portion of immunoglobulin G (IgG). FcgammaRIIIb is a
      glycosylphosphatidylinositol-linked protein expressed on neutrophils and triggers
      degranulation and opsonic phagocytosis. The extracellular region of FcgammaR is
      composed of two Ig-fold domains and can be cleaved as a soluble form
      (sFcgammaRIIIb), which is also reactive with complement receptor type 3. Although
      structure and Fc interaction of sFcgammaRIIIb have been characterized by X-ray
      crystallography, little has been known about its structure in solution. We herein
      report the backbone NMR assignments of human sFcgammaRIIIb to gain basic
      understanding of functional IgG-FcgammaRIII interactions of immunological and
      biopharmaceutical interest regarding the structural investigation.

PMID- 29453715
TI  - The influence of heavy metals, polyaromatic hydrocarbons, and polychlorinated
      biphenyls pollution on the development of antibiotic resistance in soils.
AB  - The minireview is devoted to the analysis of the influence of soil pollution with
      heavy metals, polyaromatic hydrocarbons (PAHs), and the polychlorinated biphenyls
      (PCBs) on the distribution of antibiotics resistance genes (ARGs) in soil
      microbiomes. It is shown that the best understanding of ARGs distribution process
      requires studying the influence of pollutants on this process in natural
      microbiocenoses. Heavy metals promote co-selection of genes determining
      resistance to them together with ARGs in the same mobile elements of a bacterial
      genome, but the majority of studies focus on agricultural soils enriched with
      ARGs originating from manure. Studying nonagricultural soils would clear
      mechanisms of ARGs transfer in natural and anthropogenically transformed
      environments and highlight the role of antibiotic-producing bacteria. PAHs make a
      considerable shift in soil microbiomes leading to an increase in the number of
      Actinobacteria which are the source of antibiotics formation and bear multiple
      ARGs. The soils polluted with PAHs can be a selective medium for bacteria
      resistant to antibiotics, and the level of ARGs expression is much higher. PCBs
      are accumulated in soils and significantly alter the specific structure of soil
      microbiocenoses. In such soils, representatives of the genera Acinetobacter,
      Pseudomonas, and Alcanivorax dominate, and the ability to degrade PCBs is
      connected to horizontal gene transfer (HGT) and high level of genomic plasticity.
      The attention is also focused on the need to study the properties of the soil
      having an impact on the bioavailability of pollutants and, as a result, on
      resistome of soil microorganisms.

PMID- 29453717
TI  - U-tube based near-surface environmental monitoring in the Shenhua carbon dioxide
      capture and storage (CCS) project.
AB  - The CO2 injected into deep formations during implementation of carbon dioxide
      (CO2) capture and storage (CCS) technology may leak and migrate into shallow
      aquifers or ground surfaces through a variety of pathways over a long period. The
      leaked CO2 can threaten shallow environments as well as human health. Therefore,
      almost all monitoring programs for CCS projects around the world contain near
      surface monitoring. This paper presents a U-tube based near-surface monitoring
      technology focusing on its first application in the Shenhua CCS demonstration
      project, located in the Ordos Basin, Inner Mongolia, China. First, background
      information on the site monitoring program of the Shenhua CCS demonstration
      project was provided. Then, the principle of fluid sampling and the monitoring
      methods were summarized for the U-tube sampler system, and the monitoring data
      were analyzed in detail. The U-tube based monitoring results showed that the U
      tube sampler system is accurate, flexible, and representative of the subsurface
      fluid sampling process. The monitoring indicators for the subsurface water and
      soil gas at the Shenhua CCS site indicate good stratification characteristics.
      The concentration level of each monitoring indicator decreases with increasing
      depth. Finally, the significance of this near-surface environmental monitoring
      technology for CO2 leakage assessments was preliminarily confirmed at the Shenhua
      CCS site. The application potential of the U-tube based monitoring technology was
      also demonstrated during the subsurface environmental monitoring of other CCS
      projects.

PMID- 29453718
TI  - CFD simulation of copper(II) extraction with TFA in non-dispersive hollow fiber
      membrane contactors.
AB  - This study presents computational fluid dynamics (CFD) simulation of dispersion
      free liquid-liquid extraction of copper(II) with trifluoroacetylacetone (TFA) in
      hollow fiber membrane contactor (HFMC). Mass and momentum balance Navier-Stokes
      equations were coupled to address the transport of copper(II) solute across
      membrane contactor. Model equations were simulated using COMSOL MultiphysicsTM.
      The simulation was run to study the detailed concentration distribution of
      copper(II) and to investigate the effects of various parameters like membrane
      characteristics, partition coefficient, and flow configuration on extraction
      efficiency. Once-through extraction was found to be increased from 10 to 100%
      when partition coefficient was raised from 1 to 10. Similarly, the extraction
      efficiency was almost doubled when porosity to tortuosity ratio of membrane was
      increased from 0.05 to 0.81. Furthermore, the study revealed that CFD can be used
      as an effective optimization tool for the development of economical membrane
      based dispersion-free extraction processes.

PMID- 29453716
TI  - Occurrence and assessment of the risk of ultraviolet filters and light
      stabilizers in Victorian estuaries.
AB  - This reconnaissance study was undertaken to examine the occurrence of common
      ultraviolet filters (UVF) and light stabilizers (UVLS), and preservatives in four
      different estuaries in Port Philip Bay, Victoria, for the first time. In total,
      11 UV filters, 10 UV stabilizers, 12 preservatives and a metabolite, and one
      fragrance were screened in grab samples of water and sediment using a combination
      of solid phase extraction and gas and liquid chromatography mass spectrometry
      measurement techniques. In that context, 16 of the UVF and UVLS and 5 of the
      preservatives screened were observed in water and/or sediment samples. There are
      no marine water quality guideline values for any of the fragrances, preservatives
      and UV filters and light stabilizers in Australia's current national water
      quality guidelines, so potential risk was assessed using the risk quotient (RQ)
      and toxic unit (TU) concepts. In that context, only two chemicals (OC and EHMC)
      had both an RQ above 1 and a log10TU above - 3, suggesting that few of the
      screened chemicals would have posed an individual, short-term risk to organisms
      in the waters studied at the time of sampling. However, the detection of common
      UV filters, such as 4MBC, EHMC, OC and the common preservatives 2-PE, MP, and PB
      in these Victorian estuaries highlights that the existence of personal care
      products in the environment is not just an issue for more densley populated
      countries in the northern hemisphere, but also potentially of concern in
      Australia. And, in that context, more sampling campaigns in Port Philip Bay are
      of paramount importance to assess the potential risk posed by these compounds to
      aquatic ecosystems.

PMID- 29453719
TI  - MicroRNA-411 promoted the osteosarcoma progression by suppressing MTSS1
      expression.
AB  - MicroRNAs (miRNAs) play crucial roles in the progression of different tumors. In
      our study, we investigated the expression and roles of miR-411 in human
      osteosarcoma. In this study, we first confirmed that the miR-411 expression was
      higher in the serum of patients with osteosarcoma than in the serum of healthy
      volunteers. In addition, we found that the miR-411 expression was upregulated in
      the osteosarcoma tissues compared to that in the matched normal bone tissues. We
      also demonstrated that the miR-411 expression was upregulated in the four
      osteosarcoma cell lines. Elevated expression of miR-411 promoted osteosarcoma
      cell proliferation and migration. Moreover, we identified that metastasis
      suppressor protein 1 (MTSS1) was a direct target gene of miR-411 in the
      osteosarcoma cell. We also demonstrated that the MTSS1 expression was
      downregulated in the osteosarcoma tissues compared to that in the matched normal
      bone tissues. In addition, MTSS1 expression level was inversely correlated with
      miR-411 expression in the osteosarcoma tissues. Furthermore, elevated expression
      of miR-411 enhanced the osteosarcoma cell proliferation and migration through
      inhibiting the MTSS1 expression. These data suggested that miR-411 played as
      oncogene in the osteosarcoma partly by inhibiting the MTSS1 expression.

PMID- 29453720
TI  - Cytotoxic effect of chlorpyrifos is associated with activation of Nrf-2/HO-1
      system and inflammatory response in tongue of male Wistar rats.
AB  - Repeated administration of chlorpyrifos (CPF), an organophosphate pesticide, can
      increase the risk of oral cytotoxicity. The current study was designed to assess
      the mechanism by which CPF mediates its cytotoxic effect on lingual mucosa of
      rats. Twenty-four male Wistar rats were used in the present study and divided
      into three groups: group I: healthy rats (negative control), group II: rats
      treated with CPF 1/40 LD50 (3.375 mg/kg, orally/daily) for 28 days, group III:
      rats treated with CPF 1/10 LD50 (13.5 mg/kg, orally/daily) for 28 days. At the
      end of the experiment, all rats were sacrificed by cervical dislocation under
      ketamine anesthesia. Tongue samples were dissected out at their base for
      detection of heme oxygenase-1 (HO-1) and nuclear erythroid 2-related factor 2
      (Nrf-2) by western blotting and histopathological and electron microscopic
      studies. Immunostaining was used to determine cleaved caspase 3 and the nuclear
      factor kappa B (NF-kappaB) localization. Structural and ultrastructural
      examination of treated lingual mucosa with CPF demonstrated degenerative changes
      that involved both the dorsal and ventral surfaces of the tongue as well as the
      lingual glands. CPF-treated rats demonstrated a significant increase in the
      levels of pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and
      tumor necrosis factor (TNF-alpha) in addition to a significant dose-dependent
      activation of NF-kappaB and cleaved caspase 3. Furthermore, CPF activated HO-1
      and Nrf-2 pathway in a dose-dependent manner. In conclusion, this data suggests
      that the CPF-induced cytotoxicity may be explained by NF-kappaB activated
      inflammatory cascade. In addition, CPF triggers an adaptive activation of Nrf
      2/HO-1 pathway.

PMID- 29453722
TI  - ESPR special issue on Asian environmental chemistry.

PMID- 29453721
TI  - Fenton treatment of bio-treated fermentation-based pharmaceutical wastewater:
      removal and conversion of organic pollutants as well as estimation of operational
      costs.
AB  - The Fenton process is used as a tertiary treatment to remove organic pollutants
      from the effluent of bio-treated pharmaceutical wastewater (EBPW). The optimal
      and most appropriate Fenton conditions were determined by an orthogonal array
      test and single-factor experiments. The removal of chemical oxygen demand (COD)
      was influenced by the following factors in a descending order: H2O2/Fe(II) molar
      ratio > H2O2 dosage > reaction time. Under the most appropriate Fenton conditions
      (H2O2/Fe(II) molar ratio of 1:1, H2O2 dosage of 120 mg L-1 and reaction time of
      10 min), the COD and dissolved organic carbon (DOC) were removed with
      efficiencies of 62 and 53%, respectively, which met the national discharge
      standard (GB 21903-2008) for the Lake Tai Basin, China. However, the Fenton
      treatment was inadequate for removal of N compounds, and the removal of organic
      nitrogen led to an increment in N-NH3 from 3.28 to 19.71 mg L-1. Proteins and
      polysaccharides were completely removed, and humic acids (HAs) were partly
      removed with an efficiency of 55%. Three-dimensional excitation/emission matrix
      spectra (3DEEMs) indicated complete removal of fulvic acid-like substances and
      90% reduction in the florescence intensity of humic acid-like substances. Organic
      pollutants with molecular weights (MW) > 10 kDa were completely removed, MW 5-10
      kDa were degraded into smaller MW ones, and some low molecular weight acids (MW
      0.1-1 kDa) were mineralized during the Fenton process. Some species, including
      pharmaceutical intermediates and solvents were detected by gas chromatography
      mass spectrometry (GC-MS). The operational costs of the Fenton's treatment were
      estimated to be 0.58 yuan RMB/m3 EBPW based on reagent usage and iron sludge
      treatment and disposal.

PMID- 29453723
TI  - Macroelements and heavy metals content in energy crops cultivated on contaminated
      soil under different fertilization-case studies on autumn harvest.
AB  - Heavy metals (HMs) contamination of soils is a major problem occurring worldwide.
      Utility of energy crops for biofuel feedstock production systems offers a
      feasible solution for a commercial exploitation of an arable land contaminated
      with HMs. Experiments involved field testing of Miscanthus x giganteus and
      Spartina pectinata cultivated on HMs-contaminated soil with standard NPK
      fertilizers and commercially available microbial inoculum. Biomass yield, water
      content, macronutrients (N, P, K, Mg, Ca), and heavy metal (Cd, Pb, Zn)
      concentrations in plant shoots were assessed at the end of the first and the
      second growing season. Independently of the applied fertilizers, Miscanthus x
      giganteus produced higher biomass yield while contrary results were obtained for
      S. pectinata. Higher HMs content in plants influenced the status of the mineral
      macronutrients in particular N and K. Occurrence of hasted senescence induced by
      drought in the second growing season caused reduction in the concentrations of
      all elements (except Pb), due to earlier rhizomes relocation.

PMID- 29453724
TI  - Using combined multiple techniques to characterize refractory organics during
      anammox process with mature coal chemical wastewater as influent.
AB  - This study combined spectroscopy techniques to assess the composition of
      refractory organics and highlighted the potential application of excitation
      emission matrix (EEM) fluorescence spectroscopy within future monitoring of coal
      chemical wastewater treatment by the anammox process. The results showed that the
      anammox process could effectively degrade refractory organic substances, with
      fulvic-like, UV-humic acid, and Vis-humic acid component removal efficiencies of
      43.61, 53.93, and 100%, respectively. In this study, EEM fluorescence
      spectroscopy was proven to be an effective method of assessing the removal of
      dissolved organic nitrogen during anammox treatment of mature coal chemical
      wastewater. Furthermore, remarkable accumulation (9.3-16.2%) of Ca. Kuenenia
      occurred in the anammox granules that underwent long-term cultivation in mature
      coal chemical wastewater, which provided the high nitrogen removal rate. The
      abundance of Anaerolineaceae and Bacteroides was vital in refractory organic
      degradation.

PMID- 29453725
TI  - Distribution and removal of organochlorine pesticides in waste clay bricks from
      an abandoned manufacturing plant using low-temperature thermal desorption
      technology.
AB  - The distribution of pollutants in waste clay bricks from an organochlorine
      pesticide-contaminated site was investigated, and removal of the pollutants using
      a thermal desorption technology was studied. The results showed that the contents
      of HCHs in both the surface and the inner layer of the bricks were slightly
      higher than those of DDTs. The total pore volume of the bricks was 37.7 to 41.6%
      with an increase from external to internal surfaces. The removal efficiency by
      thermal treatment was within 62 to 83% for HCHs and DDTs in bricks when the
      temperature was raised from 200 to 250  degrees C after 1 h. HCHs were more
      easily removed than DDTs with a higher temperature. Either intraparticle or
      surface diffusion controls the desorption processes of pollutants in bricks. It
      was feasible to use the polluted bricks after removal of the pollutants by low
      temperature thermal desorption technology.

PMID- 29453726
TI  - Advances in Probiotic Regulation of Bone and Mineral Metabolism.
AB  - Probiotics have been consumed by humans for thousands of years because they are
      beneficial for long-term storage of foods and promote the health of their host.
      Ingested probiotics reside in the gastrointestinal tract where they have many
      effects including modifying the microbiota composition, intestinal barrier
      function, and the immune system which result in systemic benefits to the host,
      including bone health. Probiotics benefit bone growth, density, and structure
      under conditions of dysbiosis, intestinal permeability, and inflammation
      (recognized mediators of bone loss and osteoporosis). It is likely that multiple
      mechanisms are involved in mediating probiotic signals from the gut to the bone.
      Studies indicate a role for the microbiota (composition and activity), intestinal
      barrier function, and immune cells in the signaling process. These mechanisms are
      not mutually exclusive, but rather, may synergize to provide benefits to the
      skeletal system of the host and serve as a starting point for investigation.
      Given that probiotics hold great promise for supporting bone health and are
      generally regarded as safe, future studies identifying mechanisms are warranted.

PMID- 29453727
TI  - Floating flap of internal limiting membrane in myopic macular hole surgery.
AB  - PURPOSE: To evaluate the surgical results of macular hole (MH) in patients with
      high myopia treated with pars plana vitrectomy (PPV) leaving the internal
      limiting membrane (ILM) flap floating in vitreous fluid at the edge of the MH.
      METHODS: Nine highly myopic eyes with MH of nine consecutive patients who
      underwent PPV were retrospectively evaluated. Three eyes were accompanied by
      retinal detachment (RD). ILM peeling was performed around the MH and some part of
      the ILM flap was left attached to the edge of the MH. Further manipulation of the
      ILM flap to cover the MH was not performed. Fluid-gas exchange was performed to
      the retinal vessel arcade level. Patients maintained a face down position for 3
      to 7 days postoperatively. RESULTS: Complete MH closure was confirmed using
      optical coherence tomography in all eyes and three eyes with RD showed
      reattachment of the retina after the initial surgery. Visual acuity significantly
      improved (P = 0.02) and no eyes experienced MH reopening or RD occurrence during
      the follow-up period of 8.33 +/- 3.61 months after the surgery. CONCLUSIONS: MH
      with or without RD in highly myopic eyes could be successfully treated with PPV
      leaving ILM flap floating in vitreous fluid at the edge of the MH. After the ILM
      peeling, further manipulation of the ILM flap to cover the MH would not be
      necessary for the treatment of MH in high myopia.

PMID- 29453728
TI  - Single-site port robotic-assisted hysterectomy: an update.
AB  - Single-incision approach in robotic gynecology is a relatively new concept. The
      role of single-port systems in robotic hysterectomy, their advantages and
      disadvantages, as well as the technical challenges, are still under
      investigation. A systematic review was performed by searching in PubMed and
      Scopus databases. In 810 out of 1225 patients, hysterectomy was performed for non
      neoplastic disease. Single-Site(r) was the most common port system. Duration of
      the procedure and relative blood loss ranged from 60 to 311 min and 7 to 750 ml,
      respectively. The weight of the removed uteri ranged from 39 to 520 g. 4.9% of
      the included patients presented complications, among which bleeding, vaginal
      haematoma, laceration and dehiscence, umbilical hernia, and visceral injuries.
      Conversion rate to laparotomy reached 2.8%. Although some technical difficulties
      are still described in the literature, the single-port approach is becoming more
      standardized nowadays and performed by more surgeons. The initial phase of the
      learning curve can be achieved after five cases, while a proficiency in
      intracorporeal cuff suturing after 14 cases. Uterus weight and previous abdominal
      surgical history can still be limitations of the technique. Compared to our
      previous study, we can see that the technique has been used in more elderly or
      obese patients. The complication rate can reach 4.9% while the conversion rate
      can reach 2.8%. However, we consider that complication and conversion rates as
      well as surgical time could be improved with experience. Regarding post-operative
      pain and cosmetic outcomes, the lack of information do not allow us to draw any
      safe conclusions.

PMID- 29453729
TI  - Perioperative outcomes of robotic hysterectomy with mini-laparotomy versus open
      hysterectomy for uterus weighing more than 250 g.
AB  - To compare perioperative outcomes in patients undergoing robotic hysterectomy and
      extraction of specimen via mini-laparotomy (RHML) versus open hysterectomy (OH)
      when uterus weighs more than 250 g. To study the factors determining the length
      of hospital stay in 2 groups. A retrospective analysis of all hysterectomies
      performed for uterus weighing more than 250 g from the year 2012 to 2015 was
      conducted. A total of 140 patients were divided into 2 groups based on the type
      of surgery; RHML (n = 82) and OH (n = 58). Mini-laparotomy consisted of a
      customised incision connecting 2 left lateral port sites for specimen extraction
      after completing the hysterectomy robotically. Patient factors and perioperative
      outcomes were compared using Student's t tests and Chi-square analysis. Mean
      length of stay (RHML = 1.4 days; OH = 3.4 days), estimated blood loss (EBL) (RHML
      = 119.9 ml; OH = 547.5 ml) and operative time (RHML = 191.5 min; OH = 162.8 min)
      were significantly different. No significant differences were noted for patient
      BMI, age, comorbidities, intraoperative complications, pathology of uterus and
      uterus weight. Postoperative complications were significantly different between
      two groups (RHML = 6.0%; OH = 15.5%; p = .021). None of the patients stayed less
      than 24 h in OH group compared to 59.8% patients in RHML group. Type of procedure
      (p = .004) and EBL (p = .002) significantly predicted the length of stay.
      Patients undergoing RHML have significantly shorter length of stay, EBL and
      postoperative complications than OH. The operative time for RHML was longer than
      OH, but the overall decreased length of stay overcomes this disadvantage. RHML
      approach retains the benefits of da Vinci, while simultaneously preserving the
      specimen.

PMID- 29453730
TI  - Robotic-assisted bladder diverticulectomy: point of technique to identify the
      diverticulum.
AB  - We aim to outline our technique of performing a robotic-assisted bladder
      diverticulectomy at our institution and report our surgical outcomes. We report
      the cases of three robotic-assisted bladder diverticulectomies, performed at the
      Royal Surrey County Hospital during the period of January 2014 to December 2015.
      Patient was positioned in low dorsal lithotomy position. A 6Fr double-J stent was
      prophylactically inserted at the start of the procedure. Foley catheter was
      placed over guide wire into the diverticulum and balloon inflated on the
      diverticulum neck. We used a transperitoneal extravesical approach to mobilise
      the distended bladder diverticulum, dissected en bloc and transected at the
      diverticulum neck in all cases. The bladder was closed in two layers with
      absorbable sutures. The procedures were uneventful, without post-operative
      complications and minimal blood loss. The median length of stay was 3 days and
      all three patients reported a significant improvement in all symptoms with non
      significant post-void residuals. Robotic-assisted bladder diverticulectomy is a
      safe and effective procedure that results in both symptom relief and minimal post
      void residuals.

PMID- 29453731
TI  - Patient perceptions of acute pain and activity disruption following inguinal
      hernia repair: a propensity-matched comparison of robotic-assisted, laparoscopic,
      and open approaches.
AB  - Few publications describe the potential benefit of robotic-assisted inguinal
      hernia repair on acute postoperative groin pain (APGP). This study compared
      patients' perceptions of APGP, activity limitation, and overall satisfaction
      after robotic-assisted- (R), laparoscopic (L), or open (O) inguinal hernia repair
      (IHR). Random samples of patients from two web-based research panels and surgical
      practices were screened for patients who underwent IHR between October 28, 2015
      and November 1, 2016. Qualified patients were surveyed to assess perceived APGP
      at 1 week postoperatively, activity disruption, and overall satisfaction. Three
      cohorts based on operative approach were compared after propensity matching.
      Propensity scoring resulted in 83 R-IHR matched to 83 L-IHR respondents, while 85
      R-IHR matched with 85 O-IHR respondents. R-IHR respondents recalled less APGP
      compared to respondents who had O-IHR (4.1 +/- 0.3 vs 5.6 +/- 0.3, p < 0.01) but
      similar APGP compared to L-IHR (4.0 +/- 0.3 vs 4.4 +/- 0.3, p = 0.37).
      Respondents recalled less activity disruption 1 week postoperatively after R-IHR
      versus O-IHR (6.1 +/- 0.3 vs. 7.3 +/- 0.2, p < 0.01) but similar levels of
      activity disruption after R-IHR and L-IHR (6.0 +/- 0.3 vs. 6.6 +/- 0.27, p =
      0.32). At the time of the survey, respondents perceived less physical activity
      disruption after R-IHR compared to O-IHR (1.4 +/- 0.2 vs. 2.8 +/- 0.4, p < 0.01)
      but similar between R-IHR and L-IHR (1.3 +/- 0.2 vs 1.2 +/- 0.2, p = 0.94). Most
      respondents felt satisfied with their outcome regardless of operative approach.
      Patient perceptions of pain and activity disruption differ by approach,
      suggesting a potential advantage of a minimally invasive technique over open for
      IHR. Further studies are warranted to determine long-term outcomes regarding pain
      and quality of life after IHR.

PMID- 29453732
TI  - The influence of postgraduate qualifications on educational identity formation of
      healthcare professionals.
AB  - Demand for postgraduate qualifications in medical education can be judged by the
      increase in providers worldwide over the last two decades. However, research into
      the impact of such courses on identity formation of healthcare professionals is
      limited. This study investigates the influence of such programmes on graduates'
      educational identities, practices and career progression. Informed by
      constructivist grounded theory (CGT), semi-structured interviews were conducted
      with 27 graduates (2008-2012) from one postgraduate programme, who were at
      different stages in their careers worldwide. The audio data were transcribed and
      analysed using a CGT approach. Participants enrolled in award-bearing medical
      education courses for various intrinsic and extrinsic reasons. The findings from
      this study highlight their development as educators, and educational researchers,
      leaders and learners, as their self-efficacy in educational practices and
      engagement in scholarly activities increased. Graduates attributed career
      progression to the qualification, with many being promoted into senior positions.
      They also described substantial performance attainments in the workplace. The
      findings contribute to understanding the complexity and nuances of educational
      identity formation of healthcare professionals. A qualification in medical
      education encouraged transformational changes and epistemological development as
      an educator. Awareness of these findings will inform both those considering
      enrolment and those supporting them of potential benefits of these programmes.

PMID- 29453734
TI  - Post-operative imaging assessment of non-functioning pituitary adenomas.
AB  - BACKGROUND: Non-functioning pituitary adenomas (NFAs) are the most common
      pituitary tumors. There is significant variability in clinical practice in terms
      of post-operative imaging evaluation. The objective of this manuscript is to
      provide an exhaustive review of published articles pertaining to the post
      operative imaging evaluation of NFAs. METHODS: The MEDLINE database was queried
      for studies investigating imaging for the post-operative evaluation of pituitary
      adenomas. From an initial search of 5589 articles, 37 articles were evaluated in
      detail and included in this review. RESULTS: Magnetic resonance imaging (MRI) is
      the gold standard for post-operative monitoring of NFAs, although functional
      imaging modalities may improve identification of residual tumor in conjunction
      with MRI. The residual tumor can be distinguished from post-operative changes by
      experienced practitioners using high-resolution MRI in the immediate post
      operative setting (within 1 week of surgery). However, continued imaging
      evolution in the appearance of residual tumor or resection cavity is expected up
      to 3 months post-operatively. CONCLUSIONS: Post-operative imaging appearance of
      the pituitary gland, optic apparatus, and pneumocephalus patterns, correlated
      with the clinical outcomes. Long-term, lifetime follow-up is warranted for NFA
      patients who underwent surgical resection.

PMID- 29453733
TI  - EGFP transgene: a useful tool to track transplanted bone marrow mononuclear cell
      contribution to peripheral remyelination.
AB  - Bone marrow mononuclear cells (BMMC) constitute a heterogeneous population with
      potential to promote tissue regeneration. For this reason, this cell fraction has
      recently become a therapeutic alternative to mesenchymal stem cells, as culture
      is not required and phenotypic transformations can be hence avoided. In this
      work, and in order to attain long-lasting cell labeling and study longer survival
      times, we used BMMC isolated from adult transgenic rats expressing GFP to
      reproduce our wild type model and evaluate their remyelination ability in a
      reversible model of Wallerian degeneration. RT-PCR and flow cytometry analysis
      confirmed that cells isolated from the transgenic strain exhibited similar
      expression levels of markers specific to multipotent progenitors (CD34, CD90 and
      CD105) and Schwann cells (MPZ, MBP, S100beta and p75NTR) compared to wild type
      BMMC. BMMC expressing GFP retained their migration capacity, arriving exclusively
      at the injured nerve. Most importantly, and as detected through long-lasting cell
      tracking, some of these BMMC settled in the demyelinated area, mingled with
      endogenous cells, underwent phenotypic changes and colocalized with Schwann cell
      markers MBP and S100beta. Also worth highlighting, transgenic BMMC replicated
      wild type BMMC effects in terms of MBP organization and levels. On the basis of
      these findings, BMMC isolated from transgenic animals constitute a useful tool to
      evaluate their role in peripheral nervous system demyelination-remyelination and
      the underlying mechanisms.

PMID- 29453735
TI  - Predictors of antegrade flow at internal carotid artery during carotid artery
      stenting with proximal protection.
AB  - BACKGROUND: Carotid artery stenting (CAS) with proximal occlusion effectively
      prevent distal cerebral embolism by flow arrest at internal carotid artery (ICA);
      however, the method can expose antegrade flow at ICA due to incomplete flow
      arrest. The aim of this study was to identify predictors of antegrade flow during
      CAS with proximal protection. METHODS: We retrospectively analyzed clinical and
      angiographic data among 143 lesions treated with CAS with proximal protection by
      occluding the common carotid artery (CCA) and external carotid artery (ECA). Flow
      arrest or antegrade flow at ICA was confirmed by contrast injection during
      proximal protection. RESULTS: Antegrade flow at ICA was observed in 12 lesions
      (8.4%). Compared with lesions in which flow arrest of ICA was achieved, the
      diameter of the superior thyroid artery (STA) was significantly larger (2.4 +/-
      0.34 vs. 1.4 +/- 0.68 mm, p < 0.001), and the rate of ECA branches other than the
      STA located 0-10 mm above the bifurcation was significantly higher (50 vs. 8.4%,
      p < 0.001). Results of multivariate analysis revealed that a diameter of the STA
      >= 2.3 mm (OR 44, 95% CI 8.1-237; p < 0.001) and ECA branches other than the STA
      located 0-10 mm above the bifurcation (OR 6.0, 95% CI 1.1-32; p = 0.036) were
      independent predictors of antegrade flow. CONCLUSIONS: Distal filter protection
      should be combined with proximal protection for the lesions with antegrade flow
      to prevent distal migration of the carotid debris.

PMID- 29453736
TI  - Reproductive epidemiology of glial tumors may reveal novel treatments: high-dose
      progestins or progesterone antagonists as endocrino-immune modifiers against
      glioma.
AB  - Female gender, contraceptives, and menopausal hormone replacement treatments
      containing progesterone analogues associate with higher risk of meningiomas yet
      with lower risk of gliomas. Progesterone receptor (PR) expression and
      mifepristone treatment was highly discussed for meningiomas. However, much less
      is known in regard to progesterone actions in gliomas despite PR expression
      strongly correlates with their grade. Meningiomas and gliomas may grow faster
      during gestation; but paradoxically, parousity reduces lifetime risk of gliomas
      which can be explained with dichotomous cell growth-stimulating and inhibitory
      actions of progesterone at low versus high levels. Progesterone levels gradually
      increase in gestation up to 200-fold and the incidence of highly angiogenic brain
      tumors decreases in the last trimester. Indeed, progesterone stimulates glial
      tumor cell growth at low doses (10 nM) while induces cell kill at higher doses.
      During gestation, some immune pathways are activated to protect the mother and
      the fetus against microbial pathogens. In parallel, high-dose medroxyprogesterone
      acetate (MPA) used in treatment of endometrial carcinoma decreases tumoral
      expression of PR-B and increases infiltration of cytotoxic T lymphocytes and
      natural killer cells. MPA also synergies with IL-2 in clinical treatment of renal
      cancer. In both glioma and meningioma, the dominant cytosolic PR is PR-B which
      increases cell growth, while PR-A limits cell growth. This seems also paradoxical
      at the first glance due to opposite behavior of these tumors in diverse endocrine
      conditions. High-dose progestins may inhibit brain tumor growth by downregulating
      PR-B, yet the dosage thresholds may differ between glial and meningeal tumors due
      to higher total PR expression in meningiomas. Supporting this proposal, certain
      progestins were reported to stimulate meningioma growth in anecdotal reports, but
      same agents at much higher doses reduced meningioma cell proliferation in pilot
      clinical studies. PR antagonist mifepristone reduced meningioma growth in some
      clinical studies, but lacked efficacy in others. In fact, mifepristone also has
      partial PR agonist efficacy and acts in synergy with MPA to block EC growth.
      Hence, a similar mechanism of receptor downregulation may also account for
      mifepristone. Both MPA and mifepristone also harbor myeloprotective features
      against chemotherapy. Ulipristal is another contraceptive PR antagonist and
      exerts promising anticancer activity on drug-resistant ovarian cancer and BRCA1
      mutant breast cancer cells, which can be tested in animal glioblastoma models. We
      propose that progestins strongly deserve to be investigated in experimental
      models of glioblastoma alone and in combination with immunostimulating agents.

PMID- 29453737
TI  - Two-stage hepatectomy aiming for the development of intrahepatic venous
      collaterals for multiple colorectal liver metastases.
AB  - BACKGROUND: Aggressive hepatectomy with venous resection has a higher risk of
      postoperative liver failure (POLF) than hepatectomy without venous
      reconstruction; however, venous reconstruction is technically demanding. We
      performed a novel two-stage hepatectomy (TSH) without venous reconstruction in a
      patient with bilobar multiple colorectal liver metastases located near the caval
      confluence, waiting for the development of intrahepatic venous collaterals
      between procedures. CASE PRESENTATION: A 60-year-old man was referred to our
      hospital with sigmoid colon cancer accompanied by intraabdominal abscess and two
      synchronous liver metastases. One of the liver tumors (tumor 1) was located in
      segment 8 near the caval confluence and was attached to both the right hepatic
      vein (RHV) and middle hepatic vein (MHV). The other tumor (tumor 2) in the left
      lobe invaded the umbilical portion of the portal vein. Both liver metastases
      decreased in size after four cycles of panitumumab/5-fluorouracil, leucovorin,
      and oxaliplatin (FOLFOX) therapy. Radical liver resection was planned because
      tumor 1 had not invaded the MHV. However, three-dimensional volumetric software
      showed that the non-congested volume of the future liver remnant was estimated at
      354 ml, which corresponded to 26.3% of the total liver volume. TSH was scheduled
      to avoid POLF. We first performed limited resection of segment 8 with resection
      of the RHV root. After the first hepatectomy, the development of intrahepatic
      venous collaterals between the RHV and MHV was seen on computed tomography and
      magnetic resonance imaging. The estimated non-congested future liver remnant was
      1242 ml, 78.5% of the total liver volume. Therefore, the patient underwent left
      hemihepatectomy 58 days after the first hepatectomy. We saw no adhesions around
      the porta hepatis, and the left hepatic artery and left branch of the portal vein
      were safely exposed and divided. Intraoperative Doppler ultrasonography revealed
      intrahepatic venous collaterals arising from RHV to MHV. The patient's
      postoperative course was uneventful, and he underwent eight cycles of
      panitumumab/FOLFOX therapy for 5 months after the second hepatectomy.
      CONCLUSIONS: Our TSH strategy helped avoid POLF by waiting for the development of
      intrahepatic venous collaterals.

PMID- 29453738
TI  - Friends in Activities, School-related Affect, and Academic Outcomes in Diverse
      Middle Schools.
AB  - Participating in school-based activities is linked to positive academic
      engagement and achievement, but less is known about how peer relationships within
      activities affect these outcomes. The current study examined friends in
      extracurricular activities as a predictor of academic outcomes in multiethnic
      middle schools in California. Specifically, the mediating role of school
      belonging, and interactions by ethnicity and type of activity, were examined in a
      sample including African American or Black, East or Southeast Asian, White, and
      Latino youth in extracurricular activities (N = 2268; Mage = 13.36 in eighth
      grade; 54% female). The results of multilevel mediational models suggested that
      school belonging mediated the link between friends in activities and academic
      outcomes, and these findings replicated across groups based on ethnicity and the
      type of activity in which one was involved in general. These results are
      discussed in terms of how activities can be structured to promote positive peer
      relations in ways that are linked with academic engagement and achievement.

PMID- 29453739
TI  - How is Civic Engagement Related to Personal Identity and Social Identity in Late
      Adolescents and Emerging Adults? A Person-Oriented Approach.
AB  - Adolescence and emerging adulthood are periods in life when individuals both
      question and define their place in society and form their identity. Meanwhile,
      active youth civic engagement represents a challenge for each democracy. The
      purpose of this study was to analyze the different forms of civic engagement
      among late adolescents and emerging adults and how they are related to personal
      identity and social identity, while adopting an integrative perspective through
      the lens of a person-oriented approach. The participants were 1217 (62.3% female)
      16-24 year-old French students (M age  = 19.17; SD age  = 1.83). First, derived
      from cluster analyses, the findings emphasized diversity in civic engagement,
      from strong civic participation (in different formal and informal ways) to
      various forms of passivity. Diversity was also highlighted for personal identity
      and social identity profiles. Second, a Configural Frequency Analysis revealed a
      typical pattern associating passivity in civic engagement, personal carefree
      diffusion and rejection of social identity. Overall, these findings highlight an
      absence of general youth disaffection and provide a meaningful specific pattern
      for the understanding of passivity in political and civic matters in late
      adolescence and emerging adulthood.

PMID- 29453740
TI  - Arrestins: structural disorder creates rich functionality.
AB  - Arrestins are soluble relatively small 44-46 kDa proteins that specifically bind
      hundreds of active phosphorylated GPCRs and dozens of non-receptor partners.
      There are binding partners that demonstrate preference for each of the known
      arrestin conformations: free, receptor-bound, and microtubule-bound. Recent
      evidence suggests that conformational flexibility in every functional state is
      the defining characteristic of arrestins. Flexibility, or plasticity, of proteins
      is often described as structural disorder, in contrast to the fixed
      conformational order observed in high-resolution crystal structures. However,
      protein-protein interactions often involve highly flexible elements that can
      assume many distinct conformations upon binding to different partners. Existing
      evidence suggests that arrestins are no exception to this rule: their flexibility
      is necessary for functional versatility. The data on arrestins and many other
      multi-functional proteins indicate that in many cases, "order" might be
      artificially imposed by highly non-physiological crystallization conditions
      and/or crystal packing forces. In contrast, conformational flexibility (and its
      extreme case, intrinsic disorder) is a more natural state of proteins,
      representing true biological order that underlies their physiologically relevant
      functions.

PMID- 29453741
TI  - Fuel for the Work Required: A Theoretical Framework for Carbohydrate
      Periodization and the Glycogen Threshold Hypothesis.
AB  - Deliberately training with reduced carbohydrate (CHO) availability to enhance
      endurance-training-induced metabolic adaptations of skeletal muscle (i.e. the
      'train low, compete high' paradigm) is a hot topic within sport nutrition. Train
      low studies involve periodically training (e.g., 30-50% of training sessions)
      with reduced CHO availability, where train-low models include twice per day
      training, fasted training, post-exercise CHO restriction and 'sleep low, train
      low'. When compared with high CHO availability, data suggest that augmented cell
      signalling (73% of 11 studies), gene expression (75% of 12 studies) and training
      induced increases in oxidative enzyme activity/protein content (78% of 9 studies)
      associated with 'train low' are especially apparent when training sessions are
      commenced within a specific range of muscle glycogen concentrations. Nonetheless,
      such muscle adaptations do not always translate to improved exercise performance
      (e.g. 37 and 63% of 11 studies show improvements or no change, respectively).
      Herein, we present our rationale for the glycogen threshold hypothesis, a window
      of muscle glycogen concentrations that simultaneously permits completion of
      required training workloads and activation of the molecular machinery regulating
      training adaptations. We also present the 'fuel for the work required' paradigm
      (representative of an amalgamation of train-low models) whereby CHO availability
      is adjusted in accordance with the demands of the upcoming training session(s).
      In order to strategically implement train-low sessions, our challenge now is to
      quantify the glycogen cost of habitual training sessions (so as to inform the
      attainment of any potential threshold) and ensure absolute training intensity is
      not compromised, while also creating a metabolic milieu conducive to facilitating
      the endurance phenotype.

PMID- 29453742
TI  - The Effect of Physical Activity Interventions on Glycosylated Haemoglobin (HbA1c)
      in Non-diabetic Populations: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Physical activity is widely perceived to be beneficial for preventing
      type 2 diabetes mellitus and for controlling glycaemic levels in patients with
      type 2 diabetes, but evidence supporting a positive effect in the control of
      glycaemic levels in healthy people is rather weak. The aim of this review was to
      estimate the effect of physical activity on glycaemic control measured by
      glycosylated haemoglobin (HbA1c) levels in non-diabetic populations, and to
      determine which type of physical activity has a greater influence on glycaemic
      control. METHODS: We systematically searched the MEDLINE, EMBASE, Cochrane
      Library and Web of Science databases, from inception to May 2017, for
      experimental studies addressing the effect of physical activity on glycaemic
      control measured by HbA1c levels in non-diabetic populations. The DerSimonian and
      Laird method was used to compute pooled estimates of effect size (ES) and
      respective 95% confidence intervals (CIs). The effect of physical activity on
      HbA1c levels was estimated in two ways: (1) physical activity intervention versus
      control; and (2) physical activity pre-post intervention. Additionally, subgroup
      analyses were performed based on age of participants and different aspects of the
      intervention. RESULTS: Fifteen published studies were included in the meta
      analysis. In analyses comparing physical activity intervention and control, we
      found a decrease of HbA1c levels in favour of the intervention group (ES = 0.32;
      95% CI 0.01-0.62) with substantial heterogeneity (I2 = 63.2%; p = 0.008). In the
      pre-post analysis, there was a decrease in HbA1c levels post physical activity
      intervention (ES = 0.17; 95% CI 0.01-0.33) with low heterogeneity (I2 = 25.8%; p
      = 0.164). Additionally, for physical activity intervention versus control, a
      decrease in HbA1c levels was observed in resistance exercise and in intervention
      length below 12 weeks. Furthermore, for pre-post effect analyses, a decrease in
      HbA1c levels was observed in the supervised physical activity programme, other
      type of exercises, intervention length below 12 weeks and exercise intervention
      week duration above 150 min subgroups. CONCLUSIONS: This systematic review and
      meta-analysis provides an overview of the evidence supporting physical activity
      as a suitable intervention for glycaemic control as measured by HbA1c levels in
      non-diabetic populations. TRIAL REGISTRATION: PROSPERO CRD42016050991.

PMID- 29453744
TI  - Low Serum IgE Is a Sensitive and Specific Marker for Common Variable
      Immunodeficiency (CVID).
AB  - Although small prior studies have suggested that IgE can be low in common
      variable immunodeficiency (CVID), the workup for patients with recurrent
      infections and suspected hypogammaglobulinemia does not include the routine
      measurement of serum IgE. We sought to test the hypothesis that low/undetectable
      serum IgE is characteristic of CVID by comparing the frequency of
      low/undetectable serum IgE in healthy controls and patients with CVID. We
      measured total serum IgE in a large multi-center cohort of patients with CVID (n
      = 354) and compared this to large population-based cohorts of children and
      adults. We further compared IgE levels in patients with CVID to those with other
      forms of humoral immunodeficiency, and in a subset, measured levels of allergen
      specific serum IgE and IgG subclasses. Lastly, we evaluated for the presence of
      IgE in commercially available immunoglobulin replacement therapy (IgRT) products.
      An undetectable serum IgE (< 2 IU/ml) occurs in only 3.3% (95% CI, 1.9-5.7%) of
      the general population. In contrast, an undetectable IgE occurs in 75.6% (95% CI,
      65.6-85.7%) of patients with CVID. Conversely, a high IgE (> 180 IU/ml) is very
      uncommon in CVID (0.3% of patients). IgE is > 2 IU/ml in 91.2% of patients with
      secondary hypogammaglobulinemia, and thus, an IgE < LLOD is suggestive of a
      primary humoral immunodeficiency. Allergen-specific IgE is not detectable in
      96.5% of patients with CVID. Sufficient quantities of IgE to change the total
      serum IgE are not contained in IgRT. The IgG1/IgG4 ratio is increased in subjects
      with low IgE, regardless of whether they are controls or have CVID. These
      findings support the routine measurement of serum IgE in the workup of patients
      with hypogammaglobulinemia.

PMID- 29453745
TI  - Investigating the Effectiveness, Acceptability and Impact on Healthcare Usage of
      Providing a Cognitive-Behavioural Based Psychological Therapy Service for
      Patients with Primary Antibody Deficiency.
AB  - PURPOSE: Patients with primary antibody deficiency report poorer quality of life
      and higher rates of anxiety and depression than the general population. Cognitive
      behavioral therapy has been shown to be a valuable treatment for patients with
      other long-term physical health conditions, improving well-being and enabling
      them to manage their symptoms more effectively. The aim of this project was to
      establish the feasibility and effectiveness of providing cognitive-behavioral
      based therapy to patients with primary antibody deficiency. METHODS: Forty-four
      patients completed a course of psychological therapy. Participants completed a
      series of self-report measures examining psychological and physical health, and
      service usage, prior to starting treatment and following their final session.
      They also provided feedback on their experience of treatment. RESULTS: Patients
      showed improvements in anxiety, depression, insomnia and fatigue. There was a
      high level of acceptability of the service and the potential for long-term cost
      savings to the NHS. CONCLUSION: Psychological therapy based on the cognitive
      behavioral model of treatment appears to be a valuable treatment for patients
      with primary antibody deficiency and comorbid mental health difficulties.

PMID- 29453743
TI  - Neuromuscular Control Deficits and the Risk of Subsequent Injury after a
      Concussion: A Scoping Review.
AB  - An emerging area of research has identified that an increased risk of
      musculoskeletal injury may exist upon returning to sports after a sport-related
      concussion. The mechanisms underlying this recently discovered phenomenon,
      however, remain unknown. One theorized reason for this increased injury risk
      includes residual neuromuscular control deficits that remain impaired despite
      clinical recovery. Thus, the objectives of this review were: (1) to summarize the
      literature examining the relationship between concussion and risk of subsequent
      injury and (2) to summarize the literature for one mechanism with a theorized
      association with this increased injury risk, i.e., neuromuscular control deficits
      observed during gait after concussion under dual-task conditions. Two separate
      reviews were conducted consistent with both specified objectives. Studies
      published before 9 December, 2016 were identified using PubMed, Web of Science,
      and Academic Search Premier (EBSCOhost). Inclusion for the objective 1 search
      included dependent variables of quantitative measurements of musculoskeletal
      injury after concussion. Inclusion criteria for the objective 2 search included
      dependent variables pertaining to gait, dynamic balance control, and dual-task
      function. A total of 32 studies were included in the two reviews (objective 1 n =
      10, objective 2 n = 22). According to a variety of study designs, athletes appear
      to have an increased risk of sustaining a musculoskeletal injury following a
      concussion. Furthermore, dual-task neuromuscular control deficits may continue to
      exist after patients report resolution of concussion symptoms, or perform
      normally on other clinical concussion tests. Therefore, musculoskeletal injury
      risk appears to increase following a concussion and persistent motor system and
      attentional deficits also seem to exist after a concussion. While not yet
      experimentally tested, these motor system and attentional deficits may contribute
      to the risk of sustaining a musculoskeletal injury upon returning to full
      athletic participation.

PMID- 29453746
TI  - Effect of Aerobic Exercise on Treg and Th17 of Rats with Ischemic Cardiomyopathy.
AB  - Immune activation and inflammation participate in the progression of chronic
      heart failure (CHF). Th17 cells and CD4+CD25+ regulatory T (Treg) cells both come
      from naive Th cells and share reciprocal development pathways but exhibit
      opposite effects. We hypothesized that the Th17/Treg balance was impaired in
      patients with CHF, and exercise can improve it. Rats with ischemic cardiomyopathy
      were prepared by ligaturing the left anterior descending branch of the left
      coronary artery. Rats in training group were trained with treadmill; Th17 cells
      increased significantly while Treg cells significantly decreased in s by flow
      cytometry, and the peripheral blood level of IL-6, IL-17, and TNF-alpha was
      obviously elevated by ELISA assay. We found that Th17/Treg balance is impaired in
      CHF rats, suggesting Th17/Treg imbalance potentially plays a role in the
      pathogenesis of CHF. Exercise can improve Th17/Treg imbalance, which also
      improves cardiac function of CHF.

PMID- 29453747
TI  - Clinical Applications of Patient-Specific Models: The Case for a Simple Approach.
AB  - Over the past several decades, increasingly sophisticated models of the heart
      have provided important insights into cardiac physiology and are increasingly
      used to predict the impact of diseases and therapies on the heart. In an era of
      personalized medicine, many envision patient-specific computational models as a
      powerful tool for personalizing therapy. Yet the complexity of current models
      poses important challenges, including identifying model parameters and completing
      calculations quickly enough for routine clinical use. We propose that early
      clinical successes are likely to arise from an alternative approach: relatively
      simple, fast, phenomenologic models with a small number of parameters that can be
      easily (and automatically) customized. We discuss examples of simple yet
      foundational models that have already made a tremendous impact on clinical
      education and practice, and make the case that reducing rather than increasing
      model complexity may be the key to realizing the promise of patient-specific
      modeling for clinical applications.

PMID- 29453748
TI  - Social distance in Lithuanian psychology and social work students and
      professionals.
AB  - PURPOSE: This cross-sectional study aimed to compare desire for social distance
      from people with mental illness in the disciplines of social work and psychology,
      and among students and professionals having different professional experience.
      METHODS: 948 respondents (715 students and 233 professionals) from Lithuanian
      educational and mental health-care institutions participated in an anonymous
      survey. Social distance was measured using Lithuanian Social Distance Scale which
      was created for this study. Participants also answered questions about
      familiarity with mental illness. Bias of social desirability was measured using
      the balanced inventory of desirable responding. RESULTS: Series of ANCOVA
      analysis revealed that psychology and social work master's and PhD students
      reported less social distance from people with mental illness when compared with
      bachelor's students. Familiarity with mental illness was significantly related to
      less social distance in the student sample, but not in professionals' sample. The
      strongest desire for social distance in the professionals' sample was observed in
      social workers having less than 5 years of professional practice and most
      experienced psychologists with more than 10 years of professional practice.
      CONCLUSIONS: Social distance from people with mental illness decreases through
      the study years; however, results of professional psychologists and social
      workers illustrate different trajectories in social distance through the
      professional career. The results of this study support the need for anti-stigma
      programmes and initiatives orientated towards mental health professionals.

PMID- 29453749
TI  - Lifelong robbery victimisation and mental disorders at age 18 years: Brazilian
      population-based study.
AB  - PURPOSE: Urban violence is a major problem in Brazil and may contribute to mental
      disorders among victims. The aim of this study was to assess the association
      between robbery victimisation and mental health disorders in late adolescence.
      METHODS: At age 18 years, 4106 participants in the 1993 Pelotas Birth Cohort
      Study were assessed. A questionnaire about history of robbery victimisation was
      administered, the Self-Report Questionnaire was used to screen for common mental
      disorders, and the Mini International Neuropsychiatric Interview was used to
      assess major depressive disorder and generalised anxiety disorder. Cross
      sectional prevalence ratios between lifetime robbery victimisation and mental
      disorders were estimated using Poisson regression with robust standard errors,
      adjusting for socioeconomic variables measured at birth and violence in the home
      and maltreatment measured at age 15. RESULTS: There was a dose-response
      relationship between frequency of lifetime robberies and risk of mental
      disorders. Adolescents who had been robbed three or more times had twice the risk
      (PR 2.04; 95% CI 1.64-2.56) for common mental disorders, over four times the risk
      for depression (PR 4.59; 95% CI 2.60-8.12), and twice the risk for anxiety (PR
      1.93; 95% CI 1.06-3.50), compared with non-victims, adjusting for covariates.
      Experiencing frequent robberies had greater impact on common mental disorders
      than experiencing an armed robbery. Population attributable fractions with regard
      to robbery were 9% for common mental disorders, 13% for depression, and 8% for
      anxiety. CONCLUSIONS: Robberies are associated with common mental disorders in
      late adolescence, independently of violence between family members. Reducing
      urban violence could significantly help in preventing common mental illnesses.

PMID- 29453751
TI  - Effects of ewe's milk yogurt (whole and semi-skimmed) and cow's milk yogurt on
      inflammation markers and gut microbiota of subjects with borderline-high plasma
      cholesterol levels: a crossover study.
AB  - PURPOSE: Ewe's milk yogurt is richer in proteins, minerals and short- and medium
      chain fatty acids compared to cow's milk yogurt. We aimed to evaluate the effects
      of cow's milk yogurt (CW, 3.0% fat), semi-skimmed (ES, 2.8% fat) and whole ewe's
      milk yogurts (EW, 5.8% fat) on inflammatory markers and gut microbiota in
      subjects with borderline-high plasma cholesterol. METHODOLOGY: 30 adults (16
      women) were randomized into a crossover study to consume 250 g/yogurt/day during
      three 5-week periods (4-week washouts). Plasma insulin, leptin, adhesion
      molecules, cytokines and gut microbiota composition (qPCR) were analysed. Rates
      of change were used to assess treatment effects both in the whole group and in
      subgroups of subjects with different cholesterol/HDL-c ratio (Cho-I group A: the
      top 6 women and 4 men values; Cho-I group B: remaining subjects). RESULTS: The
      yogurts showed no different effects on the inflammatory biomarkers or the
      microbiota of the whole group. However, ICAM-1 and P-selectin rates of change
      were lower after EW compared to CW and ES, respectively, in subjects of the Cho-I
      group A (P = 0.047 and P = 0.020). Women of this group showed lower MCP-1 rates
      of change after EW compared to ES and CW (P = 0.028, both). Blautia coccoides
      Eubacterium rectale decreased in women of the Cho-I group A during EW vs. ES (P =
      0.028). CONCLUSION: Ewe's yogurt effects on inflammatory markers and microbiota
      were not different from those after cow's yogurt, but the attenuation of some
      inflammatory biomarkers with ewe's whole-milk yogurt in subjects with the highest
      TC/HDL-c deserves further study.

PMID- 29453750
TI  - Administration of Lactobacillus plantarum Lp62 to dam rats at the end of delivery
      and during lactation affects TGF-beta1 level and nutritional milk composition,
      and body weight of pups.
AB  - PURPOSE: Lactobacillus plantarum Lp62 is a lactic acid bacteria strain that has
      been isolated from cocoa beans and exhibited probiotic potential. The influence
      of oral administration of L. plantarum Lp62 on the growth of rat's pups; on
      yield, cytokines and milk composition was studied. METHODS: Lactobacillus
      plantarum Lp62 is a lactic acid bacteria strain that has been isolated from cocoa
      beans. It was administered daily by gavage to Wistar rats (n = 8), from the 7th
      day before delivery and for 20 days during lactation, in a concentration of 1.44
      * 109 CFU/rat. The dam and pups were weighed and milk was collected at 12th and
      19th day for determination of protein, triglycerides, cholesterol and lactose by
      colorimetric assays. TGF-beta1 milk levels were analyzed by ELISA. The mammary
      glands of rats were removed for histological analysis. To detect statistical
      differences between the groups, tests of mean differences at a significance level
      of 5% was performed. RESULTS: Supplementation with L. plantarum L62 resulted in
      significant higher weight of pups (p < 0.05), with similar weight on dams (p >
      0.05). The milk yield was not altered by L. plantarum treatment, but the levels
      of protein, triglycerides and cholesterol were increased (p < 0.05), with no
      difference in lactose concentration (p > 0.05). Levels of TGF-beta1 were higher
      in the milk of L. plantarum treatment (p < 0.05). CONCLUSIONS: The treatment of
      dams at the end of pregnancy and lactation with L. plantarum Lp62 increased
      nutritional content of milk, probably contributing to the higher weight of the
      pups. The higher levels of TGF-beta1 in the milk, could promote immune benefits
      to the pups. Further studies in this field are needed to prove the potential use
      of L. plantarum Lp62 as a probiotic.

PMID- 29453752
TI  - Satisfied patients after shoulder arthrodesis for brachial plexus lesions even
      after 20 years of follow-up.
AB  - PURPOSE: Patients with an upper brachial plexus lesion can suffer from
      dysfunction, joint deformities and instability of the shoulder. The goal of this
      study was to determine pain, shoulder function, patient satisfaction and muscle
      strength in shoulder arthrodesis in patients with an upper brachial plexus lesion
      more than 15 years after surgery. METHODS: We retrospectively studied 12 patients
      with a brachial plexus lesion of mean age 46 years (27-61). At a mean of 19.8
      years (15.4-30.3) after shoulder arthrodesis, patient-reported outcome measures
      (PROMs), range of motion (e.g., active and passive), patient satisfaction,
      strength of the affected and non-affected side (e.g., maximum isometric strength
      in Newton in forward and retroflexion, ab- and adduction, internal and external
      rotation) and position of fusion were obtained. PROMS consisted of the Visual
      Analogue Scale (VAS; 0-100, 0 being painless) for pain and the Disabilities of
      the Arm, Shoulder and Hand Score (DASH; 0-100, 0 being the best score) for
      function. RESULTS: At latest follow-up, the median VAS pain score was 49 (0-96)
      and 0 for, respectively, the affected and unaffected side. The DASH was 15 (8
      46), meaning a reasonable to good function of the upper extremity. Active and
      passive retroflexion was significantly different (p = 0.028). All subjects stated
      that in the same situation they would undergo a shoulder arthrodesis again. The
      unaffected side was significantly stronger in every direction. Arthrodesis showed
      position of fusion of 31 degrees  (12-70) abduction, 20 degrees  (10-50) forward
      flexion and 22 degrees  (- 14 to 58) internal rotation. The unaffected side was
      significantly (p <= 0.05) stronger in every movement direction. CONCLUSION: At a
      mean of 20 years after shoulder arthrodesis, patients with an upper brachial
      plexus lesion are still satisfied with a good to moderate functional improvement.
      LEVEL OF EVIDENCE III: A retrospective cohort study.

PMID- 29453753
TI  - Pediatric astrocytic tumor grading: comparison between arterial spin labeling and
      dynamic susceptibility contrast MRI perfusion.
AB  - PURPOSE: The aim of this study was to compare arterial spin labeling (ASL) and
      dynamic susceptibility contrast (DSC) MRI perfusion with respect to diagnostic
      performance in tumor grading in pediatric patients with low- and high-grade
      astrocytic tumors (AT). METHODS: We retrospectively analyzed 37 children with
      histologically proven treatment naive low- and high-grade AT who underwent
      concomitant pre-operative ASL and DSC MRI perfusion. Studies were performed on a
      1.5 T scanner, and a pulsed technique was used for ASL. DSC data were post
      processed with a leakage correction software. Normalization of tumor perfusion
      parameters was performed with contralateral normal appearing gray matter.
      Normalized cerebral blood volume (nCBV) values in the most perfused area of each
      neoplasm were compared with normalized DSC-derived cerebral blood flow (nDSC-CBF)
      and ASL-derived cerebral blood flow (nASL-CBF) data, and correlated with WHO
      tumor grade. Statistics included Pearson's chi-square and Mann-Whitney U tests,
      Spearman's rank correlation, and receiver operating characteristic (ROC)
      analysis. RESULTS: A significant correlation was demonstrated between DSC and ASL
      data (p < 0.001). Significant differences in terms of DSC and ASL data were found
      between low- and high-grade AT (p < 0.001). ROC analysis demonstrated similar
      performances between all parameters in predicting tumor grade (nCBV: AUC 0.96, p
      < 0.001; nDSC-CBF: AUC 0.98, p < 0.001; nASL-CBF: AUC 0.96, p < 0.001).
      CONCLUSIONS: Normalized pulsed ASL performed with a 1.5 T scanner provides
      comparable results to DSC MRI perfusion in pediatric AT and may allow distinction
      between high- and low-grade AT.

PMID- 29453755
TI  - Effect of nicotine on repeated bouts of anaerobic exercise in nicotine naive
      individuals.
AB  - PURPOSE: Nicotine is a psychostimulant that is reported to be commonly
      supplemented by athletes. The purpose of the current study was to determine the
      effects of a rapidly absorbed form of nicotine on repeated bouts of anaerobic
      exercise, perception of exertion and a range of cardiovascular variables while
      monitoring side effect profiles. METHODS: Sixteen healthy, nicotine naive male
      athletes (24.1 +/- 5.3 years, 179.0 +/- 8.8 cm, 81.7 +/- 13.5 kg, BMI 25.5 +/-
      3.0, Body fat% 13.2 +/- 5.1%) completed two repeated 30 s Wingate tests with 3
      min rest between bouts following consumption of either a 5-mg oral-dispersible
      nicotine strip (NIC) or a flavour-matched placebo (PLA) in a randomised, double
      blind, cross-over design. Before the Wingate test, resting heart rate and blood
      pressure were also measured prior to and following PLA and NIC ingestion.
      RESULTS: Peak and average power output were significantly greater following NIC
      administration compared to PLA (P < 0.01). Similarly, significant increases were
      also seen in heart rate and blood pressure following NIC administration compared
      to PLA (P < 0.01). No significant effect on pre-exercise side effect score,
      reaction time, rate of perceived exertion or post exercise blood lactate levels
      were observed (P > 0.05). CONCLUSIONS: It was concluded that oral-dispersible
      nicotine strips increase repeated anaerobic performance, possibly through strong
      sympathetic stimulation, as evident by significant elevation of cardiovascular
      parameters.

PMID- 29453754
TI  - PACAP38 in human models of primary headaches.
AB  - BACKGROUND: To review the role of PACAP38 in human models of primary headaches,
      discuss possible mechanisms of PACAP38-induced migraine, and outline future
      directions. DISCUSSION: Experimental studies have established PACAP38 as a potent
      pharmacological "trigger" molecule of migraine-like attacks. These studies have
      also revealed a heterogeneous PACAP38 migraine response in migraine without aura
      patients. In addition, findings from brain imaging studies have demonstrated
      neuronal and vascular changes in migraine patients both ictally and interictally
      after PACAP38 infusion. CONCLUSION: Human migraine models have shed light on the
      importance of PACAP38 in the pathophysiology of primary headaches. These studies
      have also pointed to the PAC1 receptor and the PACAP38 molecule itself as target
      sites for drug testing. Future research should seek to understand the mechanisms
      underlying PACAP38-induced migraine. The results from an ongoing proof of concept
      randomized clinical trial may reveal the therapeutic potential of anti-PAC1
      receptor antibodies for migraine prevention.

PMID- 29453756
TI  - Acute effects of unilateral static stretching on handgrip strength of the
      stretched and non-stretched limb.
AB  - PURPOSE: To determine the effects of an acute bout of unilateral static
      stretching on handgrip strength of both the stretched and non-stretched limb. It
      was reasoned that if the non-stretched limb experienced a decrease in force
      output, further evidence for a neural mechanism to explain a post-stretch force
      reduction would be obtained as no mechanical adaptation would have occurred.
      METHODS: Thirty participants performed maximum voluntary unilateral handgrip
      contractions of both limbs before and after stretching the finger flexors of the
      strength-dominant side only. Each trial was assessed for peak force, muscle
      activity (iEMG), and rate of force generation. RESULTS: Following the stretching
      bout, peak force and iEMG decreased by 4.4% (p = 0.001) and 6.4% (p = 0.000)
      respectively in the stretched limb only. However, rate of force generation was
      significantly impaired in both the stretched (- 17.3%; p = 0.000) and non
      stretched limbs (- 10.8%; p = 0.003) 1 min post-stretch, and remained similarly
      depressed for both limbs 15 min later. CONCLUSION: Acute stretching negatively
      impacts rate of force generation more than peak force. Moreover, a reduced rate
      of force generation from the non-stretched limb indicates the presence of a cross
      over inhibitory effect through the nervous system, which provides additional
      evidence for a neural mechanism.

PMID- 29453758
TI  - Theoretical study on the optical response behavior to hydrogen chloride gas of a
      series of Schiff-base-based star-shaped structures.
AB  - Schiff-base compounds have many applications in the field of optoelectronic
      materials and chemical sensing because of their appealing coordination ability,
      and simple and easily accessible use in structural modification. Herein, five
      kinds of star-shaped Schiff-base compounds were designed and their optical
      response behavior to hydrogen chloride (HCl) gas was studied using dependent/time
      dependent density functional theory (DFT/TDDFT). Moreover, the relationship
      between structures and properties was investigated upon changing the benzene
      group into N atom or triazine group at the core-position and introducing a
      methoxyl (-OCH3) or nitro (-NO2) group into the star-shaped Schiff-bases at the
      tail of the branches. The results show that all five Schiff-bases could be
      candidates for HCl gas sensing materials. Furthermore, introducing an electron
      donating group at either the core or the tail forms a charge transfer channel
      with the electron deficient H-bonded imino group, which is convenient for charge
      transfer and subsequently promotes a red-shift in absorption spectra and
      fluorescence quenching.

PMID- 29453757
TI  - Localization of epithelial sodium channel (ENaC) and CFTR in the germinal
      epithelium of the testis, Sertoli cells, and spermatozoa.
AB  - Spermatogenesis starts within the seminiferous tubules of the testis by mitotic
      division of spermatogonia that produces spermatocytes. Meiotic division of these
      spermatocytes produces haploid spermatids that differentiate into spermatozoa. In
      this study, we examined the expression of ENaC and CFTR (a Cl- channel) in rat
      testicular sections using confocal microscopic immunofluorescence. The structural
      integrity of the seminiferous tubule sections was verified by precise phalloidin
      staining of the actin fibers located abundantly at both basal and adluminal tight
      junctions. The acrosome forming regions in the round spermatids were stained
      using an FITC coupled lectin (wheat germ agglutinin). In all phases of the germ
      cells (spermatogonia, spermatocytes, and spermatids) ENaC was localized in
      cytoplasmic pools. Prior to spermiation, ENaC immunofluorescence appeared along
      the tails of the spermatids. In spermatozoa isolated from the epididymis, ENaC
      was localized at the acrosome and a central region of the sperm flagellum. The
      mature sperm are transcriptionally silent. Hence, we suggest that ENaC subunits
      in cytoplasmic pools in germ cells serve as the source of ENaC subunits located
      along the tail of spermatozoa. The locations of ENaC is compatible with a
      possible role in the acrosomal reaction and sperm mobility. In contrast to ENaC,
      CFTR immunofluorescence was most strongly observed specifically within the
      Sertoli cell nuclei. Based on the nuclear localization of CFTR we suggest that,
      in addition to its role as an ion channel, CFTR may have an independent role in
      gene regulation within the nuclei.

PMID- 29453759
TI  - Systemic Treatment of Patients with Advanced, Unresectable Hepatocellular
      Carcinoma: Emergence of Therapies.
AB  - To date, sorafenib, a multiple tyrosine kinase inhibitor, is the only systemic
      agent approved by the FDA in the first-line treatment of patients with
      unresectable hepatocellular carcinoma (HCC). Several other tyrosine kinase
      inhibiting agents have been investigated in the first-line setting, either alone
      (sunitinib, brivanib, linifanib, and lenvatinib) or in combination with sorafenib
      (erlotinib and doxorubicin) in phase 3 trials. However, none of these studies
      demonstrated an improvement in survival over sorafenib. Many agents have also
      been tested in patients with HCC whose disease has progressed on sorafenib, but
      regorafenib is the only one to have demonstrated efficacy in this setting in a
      randomized, phase 3 trial. There were no clear survival benefits shown with
      everolimus, brivanib, or ramucirumab as second-line therapy. Nivolumab has also
      shown promising efficacy in patients with HCC who progressed on sorafenib, which
      was recently granted approval by the FDA, although larger confirmative trials may
      be considered. The treatment landscape for patients with advanced unresectable
      hepatocellular tumors has remained fairly static for the past 10 years, with
      multiple failed trials yield little change in the way these patients might be
      treated. However, recent findings for regorafenib, lenvatinib, and nivolumab have
      led to the most significant changes in the treatment paradigm in years.

PMID- 29453760
TI  - A Tale of Two Tumors: a Case of Concomitant Esophageal Squamous Papilloma and
      Granular Cell Tumor.

PMID- 29453761
TI  - Expression Level of miR-34a in Tumor Tissue from Patients with Esophageal
      Squamous Cell Carcinoma.
AB  - BACKGROUND: miR-34a has been shown to be involved in P53 regulation. In this
      study, we aimed to evaluate the expression level of miR-34a in esophageal cancer
      and compare it with that of the normal marginal tissues. METHODS: Tumor and
      marginal tissues were obtained from 50 patients with esophageal cancer. After RNA
      extraction, expression level of miR-34a was determined using SYBR green master
      mix and real-time quantitative PCR. RESULTS: It was observed that there was a
      downregulation of miR-34a in tumoral tissue of esophageal patients in comparison
      to normal marginal tissues. Moreover, the expression level of miR-34a was
      correlated with clinicopathological specifications of the patients. CONCLUSIONS:
      miR-34a may be involved in the pathogenesis and development of esophageal cancer
      and have the potential to be used as a diagnostic and therapeutic marker in
      esophageal cancer.

PMID- 29453762
TI  - Inflammatory Myofibroblastic Tumor of the Mid Common Bile Duct Masquerading as
      Cholangiocarcinoma.

PMID- 29453763
TI  - Testing the Grossman model of medical spending determinants with macroeconomic
      panel data.
AB  - Michael Grossman's human capital model of the demand for health has been argued
      to be one of the major achievements in theoretical health economics. Attempts to
      test this model empirically have been sparse, however, and with mixed results.
      These attempts so far relied on using-mostly cross-sectional-micro data from
      household surveys. For the first time in the literature, we bring in
      macroeconomic panel data for 29 OECD countries over the period 1970-2010 to test
      the model. To check the robustness of the results for the determinants of medical
      spending identified by the model, we include additional covariates in an extreme
      bounds analysis (EBA) framework. The preferred model specifications (including
      the robust covariates) do not lend much empirical support to the Grossman model.
      This is in line with the mixed results of earlier studies.

PMID- 29453764
TI  - Comparative analysis of human UCB and adipose tissue derived mesenchymal stem
      cells for their differentiation potential into brown and white adipocytes.
AB  - The differentiation potential of umbilical cord blood-derived mesenchymal stem
      cells (UCB-MSCs) into brown and white adipocytes in comparison to Adipose tissue
      derived MSCs (AD-MSCs) were investigated in order to characterize their potency
      for future cell therapies. MSCs were isolated from ten UCB samples and six
      liposuction materials. MSCs were differentiated into white and brown adipocytes
      after characterization by flow cytometry. Differentiated adipocytes were stained
      with Oil Red O and hematoxylin/eosin. The UCP1 protein levels in brown adipocytes
      were investigated by immunofluoresence and western blot analysis. Cells that
      expressed mesenchymal stem cells markers (CD34-, CD45-, CD90+ and CD105+) were
      successfully isolated from UCB and adipose tissue. Oil Red O staining
      demonstrated that white and brown adipocytes obtained from AD-MSCs showed 85 and
      61% of red pixels, while it was 3 and 1.9%, respectively for white and brown
      adipocytes obtained from UCB-MSCs. Fluorescence microscopy analysis showed strong
      uncoupling protein 1 (UCP1) signaling in brown adipocytes, especially which were
      obtained from AD-MSCs. Quantification of UCP1 protein amount showed 4- and 10.64
      fold increase in UCP1 contents of brown adipocytes derived from UCB-MSCs and AD
      MSCs, respectively in comparison to undifferentiated MSCs (P < 0.004). UCB-MSCs
      showed only a little differentiation tendency into adipocytes means it is not an
      appropriate stem cell type to be differentiated into these cell types. In
      contrast, high differentiation efficiency of AD-MSCs into brown and white
      adipocytes make it appropriate stem cell type to use in future regenerative
      medicine of soft tissue disorders or fighting with obesity and its related
      disorders.

PMID- 29453765
TI  - Statistical assessment of DNA extraction methodology for culture-independent
      analysis of microbial community associated with diverse environmental samples.
AB  - Cost-effectiveness, quality, time-effectiveness and ease of the methodology are
      the most crucial factors in isolating quality DNA from wide variety of samples.
      Thus, research efforts focusing on the development of an efficient DNA extraction
      protocol is the need of the hour. The present study therefore, focuses on
      development of an efficient, rapid and free of inhibitory substances based
      methodology for extracting metagenomic DNA from diverse environmental samples
      viz. anaerobic biogas digesta, ruminant stomach, human feces, soil, and microbial
      starter cultures used for preparation of fermented food. PCR-DGGE based analysis
      and quality metagenomic library preparation, using DNA extraction methodology,
      validates the developed protocol. The developed protocol is cost effective,
      capable of isolating DNA from small sample size (100-1000 ul), time efficient
      (1.5-2.0 h protocol) and results in significantly higher DNA yield (4-8 times
      increased yield) when compared to previously available DNA extraction method and
      a commercial DNA extraction kit. The DNA extracted from the samples using
      different protocols was evaluated based on its ability to identify diverse
      microbial species using PCR-DGGE profiles targeting variable region within the
      16S rRNA gene. The results of microbial community analysis revealed comparability
      of the developed protocol to commercial kits, in effectively identifying dominant
      representatives of the microbial community in different samples. Using the DNA
      extracted from the presented methodology, metagenomic libraries were prepared,
      which were found suitable for sequencing on Illumina platform.

PMID- 29453766
TI  - Spondylodiscitis due to Aerococcus urinae and literature review.
AB  - INTRODUCTION: Aerococccus urinae (AU) is a pathogen mainly identified in male
      urinary tract infections and responsible for bacteremia and endocarditis. To the
      best of our knowledge, there are only five patients with osteomyelitis due to AU
      described in the literature. All of them had urinary tract disease or systemic
      conditions such as diabetes, and two were associated with an endocarditis. CASE
      REPORT: We described the first case of isolated spondylodiscitis without general
      or local predisposing condition, excepted age > 65 years.

PMID- 29453767
TI  - Increasing connectivity between metapopulation ecology and landscape ecology.
AB  - Metapopulation ecology and landscape ecology aim to understand how spatial
      structure influences ecological processes, yet these disciplines address the
      problem using fundamentally different modeling approaches. Metapopulation models
      describe how the spatial distribution of patches affects colonization and
      extinction, but often do not account for the heterogeneity in the landscape
      between patches. Models in landscape ecology use detailed descriptions of
      landscape structure, but often without considering colonization and extinction
      dynamics. We present a novel spatially explicit modeling framework for narrowing
      the divide between these disciplines to advance understanding of the effects of
      landscape structure on metapopulation dynamics. Unlike previous efforts, this
      framework allows for statistical inference on landscape resistance to
      colonization using empirical data. We demonstrate the approach using 11 yr of
      data on a threatened amphibian in a desert ecosystem. Occupancy data for
      Lithobates chiricahuensis (Chiricahua leopard frog) were collected on the Buenos
      Aires National Wildlife Refuge (BANWR), Arizona, USA from 2007 to 2017 following
      a reintroduction in 2003. Results indicated that colonization dynamics were
      influenced by both patch characteristics and landscape structure. Landscape
      resistance increased with increasing elevation and distance to the nearest
      streambed. Colonization rate was also influenced by patch quality, with semi
      permanent and permanent ponds contributing substantially more to the colonization
      of neighboring ponds relative to intermittent ponds. Ponds that only hold water
      intermittently also had the highest extinction rate. Our modeling framework can
      be widely applied to understand metapopulation dynamics in complex landscapes,
      particularly in systems in which the environment between habitat patches
      influences the colonization process.

PMID- 29453768
TI  - Mental Rotation in False Belief Understanding.
AB  - This study examines the spontaneous use of embodied egocentric transformation
      (EET) in understanding false beliefs in the minds of others. EET involves the
      participants mentally transforming or rotating themselves into the orientation of
      an agent when trying to adopt his or her visuospatial perspective. We argue that
      psychological perspective taking such as false belief reasoning may also involve
      EET because of what has been widely reported in the embodied cognition
      literature, showing that our processing of abstract, propositional information is
      often grounded in concrete bodily sensations which are not apparently linked to
      higher cognition. In Experiment 1, an agent placed a ball into one of two boxes
      and left. The ball then rolled out and moved either into the other box (new box)
      or back into the original one (old box). The participants were to decide from
      which box they themselves or the agent would try to recover the ball. Results
      showed that false belief performance was affected by increased orientation
      disparity between the participants and the agent, suggesting involvement of
      embodied transformation. In Experiment 2, false belief was similarly induced and
      the participants were to decide if the agent would try to recover the ball in one
      specific box. Orientation disparity was again found to affect false belief
      performance. The present results extend previous findings on EET in visuospatial
      perspective taking and suggest that false belief reasoning, which is a kind of
      psychological perspective taking, can also involve embodied rotation, consistent
      with the embodied cognition view.

PMID- 29453769
TI  - Human papilloma virus genotyping for the cross-sectional and longitudinal
      probability of developing cervical intraepithelial neoplasia grade 2 or more.
AB  - Human papilloma virus (HPV) testing is more sensitive but less specific than
      cytology. We evaluated stand-alone genotyping as a possible triage method. During
      a multicentre randomised controlled trial comparing HPV testing to conventional
      cytology, HPV-positive women were referred to colposcopy and followed up if no
      high-grade lesion was detected. HPV-positive samples were genotyped by GP5+/GP6+
      primed polymerase chain reaction followed by reverse line blot. Genotypes were
      hierarchically ordered by positive predictive value (PPV) for CIN grade 2 or more
      (CIN2+), and grouped by cluster analysis into three groups (A, B and C in
      decreasing order). Receiver operating characteristic curves were computed. Among
      2,255 HPV-positive women with genotyping, 239 CIN2+ (including 113 CIN3+) were
      detected at baseline or during a 3-year follow-up. HPV33 had the highest PPV with
      CIN2+ and CIN3+ as the endpoint and when considering lesions detected at baseline
      or also during follow-up. HPV16 and HPV35 were the second and third,
      respectively. Cross-sectional sensitivity for CIN2+ at baseline was 67.3% (95% CI
      59.7-74.2), 91.8% (95% CI 86.6-95.5) and 94.7% (95% CI 90.2-97.6), respectively,
      when considering as "positive" any of the HPV types in group A (33, 16 and 35), A
      or B (31, 52, 18, 59 and 58) and A or B or C (39, 51, 56, 45 and 68). The
      corresponding cross-sectional PPVs for CIN2+ were 15.8% 95% (CI 13.2-18.7), 12.0%
      (95% CI 10.3-13.9) and 9.6% (95% CI 8.2-11.1), respectively. HPV33, 16 and 35
      confer a high probability of CIN2+ but this rapidly decreases when adding other
      genotypes.

PMID- 29453770
TI  - Nivolumab-induced lichenoid dermatitis occurring in a patient with metastatic
      melanoma successfully treated with alitretinoin.

PMID- 29453771
TI  - Rapid improvement of nail matrix psoriasis with apremilast: clinical and
      ultrasonographic assessment.

PMID- 29453772
TI  - Effect of incision design on interproximal bone loss of teeth adjacent to single
      implants. A randomized controlled clinical trial comparing intrasulcular vs
      paramarginal incision.
AB  - PURPOSE: To evaluate the effect of incision design in implant surgery on
      interproximal bone loss of posterior teeth adjacent to interdental single
      implants, comparing intrasulcular and paramarginal incision. A further aim was to
      assess the influence of the incision technique on peri-implant bone remodeling.
      MATERIALS AND METHODS: A controlled randomized clinical trial was carried out in
      a University Clinic. All the patients received an interdental posterior single
      implant. The incision type was randomly divided into two groups: (a)
      intrasulcular or (b) paramarginal. Standardized periapical digital radiographs
      were made with the parallel technique and a silicone index individualized in each
      patient. Radiographs were made immediately after implant placement, at abutment
      connection, 6 and 12 months post-loading. Two radiographic reference points were
      detected at the interproximal aspect of the adjacent teeth: (A) the cementoenamel
      junction and (B) the most coronal aspect of the bone crest. The interproximal
      bone loss of the adjacent teeth was calculated as the difference from A to B
      between the different follow-up periods and baseline. Two different examiners
      evaluated the radiographic measurements twice. RESULTS: Sixty patients, each with
      one implant, were included, 30 in each group. A mean interproximal bone loss in
      teeth of 0.09 mm in the intrasulcular and 0.10 mm in the paramarginal group was
      found at 12 months post-loading. Mean peri-implant bone remodeling was 0.17 mm in
      the intrasulcular group and 0.15 mm in the paramarginal group. Differences
      between incision types were not statistically significant (p > .05). CONCLUSIONS:
      Both incision designs used to place interdental single implants resulted in
      minimum bone loss at the interproximal aspect of adjacent teeth. The incision
      design did not significantly influence the radiographically assessed
      interproximal bone loss nor peri-implant bone remodeling.

PMID- 29453773
TI  - Electrospray ionization source with a rear extractor.
AB  - A new electrospray source design is introduced by having an extractor electrode
      placed at 1 to 2 mm behind the emitter tip. The extractor was integrated into the
      sprayer body as a single device. An insulating tube was used to isolate the
      emitter from the extractor and to deliver the sheath gas for the electrospray.
      The electric field strength at the emitter was primarily determined by the
      relative position and the potential between the needle and the extractor;
      therefore, the spraying condition was insusceptible to the change of sprayer
      position or orientation with respect to the ion sampling inlet. Such design
      allowed the use of much lower operating voltage and facilitated the optimization
      of sprayer position by keeping the electric field parameter constant. Using an
      emitter capillary of 150 and 310 MUm in inner and outer diameters, strong ion
      signal could still be acquired with 2-kV emitter potential even if the distance
      between the emitter and ion inlet was extended to >70 mm. Charge reduction of
      protein ions using 2 extractor-based electrosprays of opposite emitter polarities
      was also demonstrated.

PMID- 29453774
TI  - Hobnail (retiform-Dabska) hemangioendothelioma located in the jejunum.

PMID- 29453775
TI  - Effect of PPARG on AGEs-induced AKT/MTOR signaling-associated human chondrocytes
      autophagy.
AB  - Accumulation of advanced glycation end products (AGEs) in articular cartilage is
      thought to represent a major risk factor for osteoarthritis development. In this
      study we aimed to probe the role of AGEs in human chondrocytes and to determine
      the impact of the peroxisome proliferator-activated receptor-gamma (PPARG) on
      AGEs-induced cell autophagy. Cell viability was measured after human chondrocytes
      were treated with different concentrations of AGEs with or without the PPARG
      inhibitor, T0070907, or agonist, pioglitazone. Autophagy activation markers
      (MAP2LC3, BECN1 and SQSTM1/P62), expression of PPARG and the phosphorylation
      levels of Akt/MTOR were determined by Western blotting; autophagosome formation
      was analyzed by transmission electron microscopy (TEM); autophagic flux was
      detected with mRFP-GFP-LC3 tandem construct. Low doses of AGEs over a short
      amount of time stimulated chondrocyte proliferation and autophagy by limiting
      phosphorylation of Akt/MTOR signaling. The addition of PPARG inhibitor T0070907
      lead to defective autophagy. High dose and long exposure to AGEs inhibited cell
      viability and autophagy by increasing phosphorylation levels of Akt/MTOR
      signaling. The agonist, pioglitazone, was shown to protect cell autophagy in a
      dose-dependent manner. Our findings suggest AGEs can downregulate PPARG and that
      PPARG maintains cell viability by activating the Akt/MTOR signaling pathway as
      well as inducing chondrocyte autophagy.

PMID- 29453776
TI  - Syndromic sebaceous nevus: current findings.
AB  - BACKGROUND: Sebaceous nevus is a congenital malformation of the skin that usually
      occurs on the scalp or face. Syndromic forms do rarely exist with associated
      cerebral and ocular malformations. The skin lesions are pale at birth and become
      irregular by puberty. In the adult patient, tumors (usually benign) develop from
      sebaceous nevus. Their surgical excision during childhood can give a better
      result in terms of the definitive scar. OBJECTIVES: The aim of this study is to
      analyze our cases of syndromic sebaceous hamartoma, perform a review of the
      existing literature, and propose guidelines for the therapeutic plan. METHODS:
      This is a retrospective study reviewing the cases of syndromic sebaceous nevus
      treated in the Department of Orthopedic Plastic Pediatric Surgery in Montpellier,
      France, and the Department of Pediatric Surgery in Lausanne, Switzerland, between
      1994 and 2016. RESULTS: The files of six patients with syndromic sebaceous nevus
      were analyzed. The average age at the first consultation was 4 months. The
      location was craniofacial in all cases. Cerebral radiological imaging was
      performed on all patients; two showed abnormal findings. Four patients underwent
      ophthalmic examination, which all revealed abnormalities. Three patients had
      other associated malformations. Three patients presented with epilepsy or
      learning difficulties in the course of follow-up. CONCLUSION: All patients
      presenting with extensive sebaceous nevus of the craniofacial region should
      benefit from cerebral imagery and ophthalmic examination since there is a very
      high probability of associated abnormalities. The developmental problems
      encountered could not be definitively associated with the skin malformations.

PMID- 29453777
TI  - Intramuscular allopregnanolone and ganaxolone in a mouse model of treatment
      resistant status epilepticus.
AB  - Allopregnanolone (5alpha-pregnan-3alpha-ol-20-one) and its synthetic 3beta-methyl
      analog, ganaxolone, are positive allosteric modulators of synaptic and
      extrasynaptic gamma-aminobutyric acid (GABA)A receptors that exhibit antiseizure
      activity in diverse animal seizure models, including models of status epilepticus
      (SE). The 2 neuroactive steroids are being investigated as treatments for SE,
      including as a treatment for SE induced by chemical threat agents. Intramuscular
      injection is the preferred route of administration in the prehospital treatment
      of SE. The objective of this study was to assess the efficacy of intramuscular
      allopregnanolone and ganaxolone in the treatment of SE induced by the chemical
      threat agent tetramethylenedisulfotetramine (TETS). The test agents were
      administered 40 minutes after the onset of SE when mice are refractory to
      treatment. Allopregnanolone and ganaxolone (each at 3 mg/kg) terminated SE in,
      respectively, 92% and 75% of animals, and prevented mortality in 85% and 50% of
      animals; the mean times to termination of behavioral seizures were, respectively,
      172 +/- 16 and 447 +/- 52 seconds. In a separate series of experiments, mice were
      dosed with the neuroactive steroids by intramuscular injection, and plasma and
      brain levels were sampled at various time points following injection to estimate
      pharmacokinetic parameters. Plasma Cmax (maximum concentration) values for
      allopregnanolone and ganaxolone were 645 and 550 ng/mL, respectively. Brain
      exposure of both steroids was approximately 3-fold the plasma exposure. Two
      compartment pharmacokinetic analysis revealed that the central compartment Vd
      (volume of distribution), CL (clearance), t1/2 (terminal half-life), and F
      (intramuscular bioavailability) values for allopregnanolone and ganaxolone were,
      respectively, 4.95 L/kg 12.88 L/kg/h,16 minutes, 97%, and 5.07 L/kg, 8.35 L/kg/h,
      25 minutes, 95%. Allopregnanolone and ganaxolone are effective in the treatment
      of TETS-induced SE when administered by the intramuscular route. Allopregnanolone
      is more rapidly acting and modestly more effective, possibly because it has
      greater potency on GABAA receptors.

PMID- 29453778
TI  - 'I'm happy to own my implicit biases': Public encounters with the implicit
      association test.
AB  - The implicit association test (IAT) and concept of implicit bias have
      significantly influenced the scientific, institutional, and public discourse on
      racial prejudice. In spite of this, there has been little investigation of how
      ordinary people make sense of the IAT and the bias it claims to measure. This
      article examines the public understanding of this research through a discourse
      analysis of reactions to the IAT and implicit bias in the news media. It
      demonstrates the ways in which readers interpreted, related to, and negotiated
      the claims of IAT science in relation to socially shared and historically
      embedded concerns and identities. IAT science was discredited in accounts that
      evoked discourses about the marginality of academic preoccupations, and helped to
      position test-takers as targets of an oppressive political correctness and
      psychologists as liberally biased. Alternatively, the IAT was understood to have
      revealed widely and deeply held biases towards racialized others, eliciting
      accounts that took the form of psychomoral confessionals. Such admissions of bias
      helped to constitute moral identities for readers that were firmly positioned
      against racial bias. Our findings are discussed in terms of their implications
      for using the IAT in prejudice reduction interventions, and communicating to the
      public about implicit bias.

PMID- 29453779
TI  - Mitochondrial cytochrome P450 (CYP) 1B1 is responsible for melatonin-induced
      apoptosis in neural cancer cells.
AB  - Melatonin is an endogenous indoleamine with a wide range of biological functions
      in the various organisms from bacteria to mammals. Evidence indicates that
      melatonin facilitates apoptosis in cancer cells and enhances the antitumor
      activity of chemotherapy in animals and clinical studies. However, the melatonin
      metabolism and the key metabolic targets in cancer cells still remain unknown. In
      this study, U118 and SH-SY5Y tumor cell lines were used to investigate the
      metabolic pathways of melatonin in cancer cells. Interestingly, the inhibitory
      effect of melatonin on proliferation in SH-SY5Y cells is more potent than that in
      U118 cells. In contrast, this inhibitory effect on the normal cells is absent.
      The antitumor effects of melatonin are positively associated with its metabolite
      N-acetylserotonin (NAS). Unexpectedly, CYP1B1 is, for first time, identified to
      localize in the mitochondria of tumor cells, and it metabolizes melatonin to form
      NAS in situ, which subsequently triggers mitochondria-dependent apoptosis in
      cancer cells. In normal cells, NAS does not induce apoptosis. A remarkable
      individual variation on CYP1B1 expression was also detected in human tumor
      tissue. These findings provide the novel mechanisms regarding the antitumor
      effects of melatonin in the level of mitochondria. Thus, we hypothesize that
      CYP1B1 overexpression in mitochondria would significantly enhance the antitumor
      effects of melatonin. Mitochondrial CYP1B1 can potentially serve as a specific
      target to modify the therapeutic and biological effects of melatonin on cancer
      patients.

PMID- 29453780
TI  - Bone-conditioned medium modulates the osteoconductive properties of collagen
      membranes in a rat calvaria defect model.
AB  - OBJECTIVES: Collagen membranes are not limited to be occlusive barriers as they
      actively support bone regeneration. However, the impact of bone-derived growth
      factors on their osteoconductive competence has not been examined. METHODS:
      Twenty adult Sprague Dawley rats were included in the study. Calvaria defects
      with a diameter of five millimeter were created. The defect was covered with one
      layer of a collagen membrane previously soaked in conditioned medium of porcine
      bone chips or in culture medium alone. After 4 weeks, microcomputed tomography
      was performed. Undecalcified thin-ground sections were subjected to light and
      scanning electron microscopy. Primary outcome parameter was the bone volume in
      the defect. Unit of analysis was the bone-conditioned medium (BCM). RESULTS: In
      the central defect area of the control and the BCM group, median new bone
      connected to the host bone was 0.54 and 0.32 mm3, respectively (p = .10). In the
      ectocranial defect area, the control group showed significantly more bone than
      the BCM group (0.90 and 0.26 mm3; p = .02). Based on an exploratory
      interpretation, the control group had smaller bony islands than the BCM group.
      Scanning electron microscopy and histology indicate the formation of bone but
      also the collagen membrane to be mineralized in the defect site. CONCLUSIONS:
      These results demonstrate that the commercial collagen membrane holds an
      osteoconductive competence in a rat calvaria defect model. Soaking collagen
      membranes with BCM shifts bone formation toward the formation of bony islands
      rather than new bone connected to the host bone.

PMID- 29453781
TI  - Commemoration in crisis: A discursive analysis of who 'we' and 'they' have been
      or become in ceremonial political speeches before and during the Greek financial
      downturn.
AB  - This study analyses the discourse of statements of the leaders of two Greek
      political parties commemorating the restoration of Greek democracy on 24 July
      1974; the ruling party New Democracy and the opposition, Coalition of the Radical
      Left. We focus on how these leaders act as entrepreneurs of their identities by
      constructing their ingroups in broad or narrow terms and their outgroups in vague
      or specific terms. These constructions were ventured during a period of relative
      political stability (2008) and instability (2012), and we focus on how ingroup
      prototypes and group boundaries are narrated across Greece's past, present and
      future in ambiguous or concrete terms. The study aligns the social identity
      approach to political leadership with studies on political discourse and 'the
      rhetoric of we'. We view commemorative statements as historical charters and
      respond to calls for discourse analysis to take greater account of historical
      context. The findings suggest concrete hypotheses about how leaders with
      different amounts of political support might define, as identity entrepreneurs,
      who 'we' are, and who 'we' are not in democratic contexts marked by stability or
      crisis.

PMID- 29453782
TI  - Unusual spontaneous porto-systemic shunt: The importance of diagnosing non
      anatomical porto-systemic shunts to improve portal flow in pediatric living
      related liver transplantation. Case report.
AB  - Collateral circulation secondary to liver cirrhosis may cause the development of
      large PSSs that may steal flow from the main portal circulation. It is important
      to identify these shunts prior to, or during the transplant surgery because they
      might cause an insufficient portal flow to the implanted graft. There are few
      reports of "steal flow syndrome" cases in pediatrics, even in biliary atresia
      patients that may have portal hypoplasia as an associated malformation. We
      present a 12-month-old female who received an uneventful LDLT from her mother,
      and the GRWR was 4.8. During the early post-operative period, she became
      hemodynamically unstable, developed ascites, and altered LFT. The post-operative
      ultrasound identified reversed portal flow, finding a non-anatomical PSS. A 3D CT
      scan confirmed the presence of a mesocaval shunt through the territory of the
      right gonadal vein, draining into the right iliac vein, with no portal inflow
      into the liver. The patient was re-operated, and the shunt was ligated. An
      intraoperative Doppler ultrasound showed adequate portal inflow after the
      procedure; the patient evolved satisfactorily and was discharged home on day
      number 49. The aim was to report a case of post-operative steal syndrome in a
      pediatric recipient due to a mesocaval shunt not diagnosed during the
      pretransplant evaluation.

PMID- 29453783
TI  - Affordances after spinal cord injury.
AB  - Spinal cord injury can cause cognitive impairments even when no cerebral lesion
      is appreciable. As patients are forced to explore the environment in a non
      canonical position (i.e., seated on a wheelchair), a modified relation with space
      can explain motor-related cognitive differences compared to non-injured
      individuals. Peripersonal space is encoded in motor terms, that is, in relation
      to the representation of action abilities and is strictly related to the
      affordance of reachability. In turn, affordances, the action possibilities
      suggested by relevant properties of the environment, are related to the
      perceiver's peripersonal space and motor abilities. One might suppose that these
      motor-related cognitive abilities are compromised when an individual loses the
      ability to move. We shed light on this issue in 10 patients with paraplegia and
      20 matched controls. All have been administered an affordances-related
      reachability judgement task adapted from Costantini, Ambrosini, Tieri,
      Sinigaglia, and Committeri (2010, Experimental Brain Research, 207, 95) and
      neuropsychological tests. Our findings demonstrate that patients and controls
      show the same level of accuracy in estimating the location of their peripersonal
      space boundaries, but only controls show the typical overestimation of reaching
      range. Secondly, patients show a higher variability in their judgements than
      controls. Importantly, this finding is related to the patients' ability to
      perform everyday tasks. Finally, patients are not faster in making their
      judgements on reachability in peripersonal space, while controls are. Our results
      suggest that not moving freely or as usual in the environment impact decoding of
      action-related properties even when the upper limbs are not compromised.

PMID- 29453784
TI  - Electrospray mass spectrometry and molecular modeling study of formation and
      stability of silver complexes with diazaperylene and bisisoquinoline.
AB  - The complex formation of the following diazaperylene ligands (L) 1,12
      diazaperylene 1, 1,1'-bisisoquinoline 2, 2,11-disubstituted 1,12-diazaperylenes
      (alkyl = methyl, ethyl, isopropyl, 3, 5, 7), 3,3'-disubstituted 1,1'
      bisisoquinoline (alkyl = methyl, ethyl, isopropyl, 4, 6, 8 and with R = phenyl,
      11 and with pyridine 12), and the 5,8-dimethoxy-substituted diazaperylene 9, 6,6'
      dimethoxy-substituted bisisoquinoline 10 with AgBF4 was investigated. Collision
      induced dissociation measurements were used to evaluate the relative stabilities
      of the ligands themselves and for the [1:1]+ complexes as well as for the
      homoleptic and heteroleptic silver [1:2]+ complexes in the gas phase. This method
      is very useful in rapid screening of the stabilities of new complexes in the gas
      phase. The influence of the spatial arrangement of the ligands and the type of
      substituents employed for the complexation were examined. The effect of the
      preorganization of the diazaperylene on the threshold activation voltages and
      thus of the relative binding energies of the different complexes are discussed.
      Density functional theory calculations were used to calculate the optimized
      structures of the silver complexes and compared with the stabilities of the
      complexes in the gas phase for the first time.

PMID- 29453785
TI  - Assessment of antiplaque effectiveness of chlorhexidine-soaked gauze compared to
      chlorhexidine mouth rinse: Randomized clinical trial.
AB  - AIM: The aim of the present study was to compare the efficacy of a disposable
      gauze soaked with chlorhexidine and rolled up on the finger vs chlorhexidine
      mouth rinse (CM) to maintain oral hygiene. METHODS: In this single-blind,
      randomized trial, both groups were instructed to brush their teeth and use the
      0.12% chlorhexidine intervention twice per day (experimental group: toothbrushing
      + chlorhexidine-soaked gauze; control group: toothbrushing + mouth rinse). The
      main outcome was the change in full mouth plaque index scores from baseline to 2
      weeks. Secondary outcomes were the patient's appreciation (visual analog scale)
      and the bleeding index. RESULTS: The final sample consisted of 60 young patients:
      31 in the experimental group and 29 in the control group. After 2 weeks, both
      interventions were effective in reducing plaque index. The percentage of score
      reduction was 33% in the experimental group and 30% for the controls, with no
      significant difference between groups. Both interventions reduced the bleeding
      index, but this reduction was significant only in the experimental group (P <
      .001). CONCLUSIONS: There is no difference between chlorhexidine-soaked gauze and
      CM regarding plaque control. In addition, gauze soaked with chlorhexidine was
      significantly more effective in reducing the bleeding index score and was
      appreciated by the patients.

PMID- 29453786
TI  - Long-term outcomes of 6-mm diameter fully covered self-expandable metal stents in
      benign refractory pancreatic ductal stricture.
AB  - BACKGROUND AND AIM: Fully covered self-expandable metal stent (FCSEMS) placement
      has been tried for pancreatic ductal strictures in chronic pancreatitis. However,
      the long-term outcome of this procedure remains unknown. The present study aimed
      to investigate the procedural and long-term outcomes of FCSEMS placement in
      patients with benign refractory pancreatic ductal strictures. METHODS: Between
      August 2011 and September 2015, 18 patients underwent endoscopic treatment with
      FCSEMS for benign refractory pancreatic ductal stricture. Technical success,
      clinical success, radiological success, and adverse events were assessed.
      RESULTS: Stent placement was successful in all patients (technical success rate,
      100%). Reduction in pain score of >50% was achieved in 15 of the 18 patients
      (clinical success rate, 83.3%). In all patients, stents could easily be removed
      at a median of 7.5 months (interquartile range [IQR], 6-13.6) after their
      insertion. FCSEMS migration did not develop in any patient. Ductal stricture was
      improved in 15 patients (radiological success rate, 83.3%). After definite stent
      removal, 13 of the 15 (86.7%) patients who had responded to pancreatic stenting
      maintained the response during follow up (median of 47.3 months; IQR, 7.4-57.1).
      CONCLUSIONS: FCSEMS placement appears to be safe and effective for the treatment
      of benign refractory pancreatic ductal strictures as it can provide persistent
      improvement in the stricture in long-term follow up.

PMID- 29453788
TI  - Hard and soft tissue changes around implants activated using plasma of argon: A
      histomorphometric study in dog.
AB  - OBJECTIVE: To histologically assess the hard and soft tissue changes after
      insertion of cleaned and activated titanium implants using plasma of argon.
      MATERIALS AND METHODS: Eight dogs were included in this study. The mandibular
      premolars and first molars were extracted. For each hemi-mandible, four implants,
      7 mm long and 3.3 mm of diameter, with a ZirTi surface were used. The surface of
      two implants was randomly treated with argon plasma (test), while the other two
      implants were left untreated (control). After 1 month, the same procedure was
      performed in the contralateral hemi-mandible. The amount of old bone, new bone,
      overall value of old bone plus new bone, and soft tissue was histologically
      evaluated. RESULTS: After 1 month of healing, high percentages of new bone in
      close contact with the implant surface were found at both the treated (60.1% +/-
      15.6%; 95% CI 56.5%-78.0%) and untreated (57.2% +/- 13.1%; 95% CI 49.3%-67.5%)
      implants. Low percentages of old bone were found at this stage of healing, at
      both the treated (4.4% +/- 3.0%; 95% CI 1.2%-5.4%) and untreated (3.4% +/- 3.1%;
      95% CI 0.6%-4.9%) implants. Not statistically significant differences were found
      between groups (p > .05). After 2 months of healing, treated implants presented a
      significantly higher (p = .012) new bone formation (72.5% +/- 12.4%; 95% CI 69.6%
      86.8%) compared to untreated sites (64.7% +/- 17.3%; 95% CI 59.4%-83.3%).
      Controversially, no difference (p = .270) in terms of old bone was present
      between treated (3.1% +/- 1.7%, 95% CI 1.8%-4.2%) and untreated implants (3.8% +/
      1.9%, 95% CI 3.2%-5.8%). Significant differences (p = .018) in terms of total
      mineralized bone were found between treated (75.6% +/- 13.0%, 95% CI 73.3%-91.3%)
      and untreated implants (68.4% +/- 16.8%; 95% CI 64.2%-87.6%). CONCLUSIONS:
      Implants treated using plasma of argon was demonstrated to reach a higher bone-to
      implant contact when compared to untreated implants.

PMID- 29453787
TI  - A phase II trial of riluzole, an antagonist of metabotropic glutamate receptor 1
      (GRM1) signaling, in patients with advanced melanoma.
AB  - Studies demonstrate that GRM, expressed by >60% of human melanomas, may be a
      therapeutic target. We performed a phase II trial of 100 mg PO bid of riluzole,
      an inhibitor of GRM1 signaling, in patients with advanced melanoma with the
      primary endpoint of response rate. Thirteen patients with GRM1-positive tumors
      were enrolled. No objective responses were observed, and accrual was stopped.
      Stable disease was noted in six (46%) patients, with one patient on study for 42
      weeks. Riluzole was well tolerated, with fatigue (62%) as the most common adverse
      event. Downregulation of MAPK and PI3K/AKT was noted in 33% of paired tumor
      biopsies. Hypothesis-generating correlative studies suggested that downregulation
      of angiogenic markers and increased leukocytes at the active edge of tumor
      correlate with clinical benefit. Pharmacokinetic analysis showed interpatient
      variability consistent with prior riluzole studies. Future investigations should
      interrogate mechanisms of biologic activity and advance the development of agents
      with improved bioavailability.

PMID- 29453791
TI  - Acceptability of health care interventions: A theoretical framework and proposed
      research agenda.

PMID- 29453789
TI  - Psychotic experiences and religiosity: data from the WHO World Mental Health
      Surveys.
AB  - OBJECTIVES: Religiosity is often associated with better health outcomes. The aim
      of the study was to examine associations between psychotic experiences (PEs) and
      religiosity in a large, cross-national sample. METHODS: A total of 25 542 adult
      respondents across 18 countries from the WHO World Mental Health Surveys were
      assessed for PEs, religious affiliation and indices of religiosity, DSM-IV mental
      disorders and general medical conditions. Logistic regression models were used to
      estimate the association between PEs and religiosity with various adjustments.
      RESULTS: Of 25 542 included respondents, 85.6% (SE = 0.3) (n = 21 860)
      respondents reported having a religious affiliation. Overall, there was no
      association between religious affiliation status and PEs. Within the subgroup
      having a religious affiliation, four of five indices of religiosity were
      significantly associated with increased odds of PEs (odds ratios ranged from 1.3
      to 1.9). The findings persisted after adjustments for mental disorders and/or
      general medical conditions, as well as religious denomination type. There was a
      significant association between increased religiosity and reporting more types of
      PEs. CONCLUSIONS: Among individuals with religious affiliations, those who
      reported more religiosity on four of five indices had increased odds of PEs.
      Focussed and more qualitative research will be required to unravel the
      interrelationship between religiosity and PEs.

PMID- 29453790
TI  - Amyloid-beta 1-40 is associated with alterations in NG2+ pericyte population ex
      vivo and in vitro.
AB  - The population of brain pericytes, a cell type important for vessel stability and
      blood brain barrier function, has recently been shown altered in patients with
      Alzheimer's disease (AD). The underlying reason for this alteration is not fully
      understood, but progressive accumulation of the AD characteristic peptide amyloid
      beta (Abeta) has been suggested as a potential culprit. In the current study, we
      show reduced number of hippocampal NG2+ pericytes and an association between NG2+
      pericyte numbers and Abeta1-40 levels in AD patients. We further demonstrate,
      using in vitro studies, an aggregation-dependent impact of Abeta1-40 on human
      NG2+ pericytes. Fibril-EP Abeta1-40 exposure reduced pericyte viability and
      proliferation and increased caspase 3/7 activity. Monomer Abeta1-40 had quite the
      opposite effect: increased pericyte viability and proliferation and reduced
      caspase 3/7 activity. Oligomer-EP Abeta1-40 had no impact on either of the
      cellular events. Our findings add to the growing number of studies suggesting a
      significant impact on pericytes in the brains of AD patients and suggest
      different aggregation forms of Abeta1-40 as potential key regulators of the brain
      pericyte population size.

PMID- 29453792
TI  - Impact of TSH during the first trimester of pregnancy on obstetric and foetal
      complications: Usefulness of 2.5 mIU/L cut-off value.
AB  - OBJECTIVE: An association of pregnancy outcomes with subclinical hypothyroidism
      has been reported; however, there still exists a strong controversy regarding
      whether subclinical hypothyroidism ought to be dealt with or not. The objective
      of the study was to evaluate the association of foetal-maternal complications
      with first trimester maternal Thyrotropin (TSH) values. DESIGN: A retrospective
      study in a single tertiary care hospital was performed. PATIENTS: A total of 1981
      pregnant women were studied during 2012. MEASUREMENTS: Thyrotropin (TSH)
      universal screening was performed between 9 and 12 weeks of gestation. Outcomes
      included foetal-maternal complications and newborn health parameters. RESULTS:
      Median TSH was 1.72 (0.99-2.61) mIU/L. The incidence of perinatal loss,
      miscarriage and stillbirth was 7.2%, 5.9% and 1.1%, respectively. Median TSH of
      women with and without miscarriage was 1.97 (1.29-3.28) vs 1.71 (0.96-2.58) mIU/L
      (P = .009). Incidence of pre-eclampsia was 3.2%; TSH in these women was 2.10
      (1.40-2.74) vs 1.71 (0.98-2.59) mIU/L in those without (P = .027). TSH in women
      with dystocia in labour was 1.76 (1.00-2.53) vs 1.68 (0.94-2.59) mIU/L in those
      who gave birth with normal progression (P = .044). Women with TSH 2.5-5.1 mIU/L
      had a higher risk of perinatal loss [OR 1.589 (1.085-2.329)], miscarriage [OR
      1.702 (1.126-2.572)] and premature birth [OR 1.39 (1.013-1.876)], adjusted by
      mother's age. There was no association with the other outcomes analysed.
      CONCLUSIONS: There is a positive association between maternal TSH in the first
      trimester of pregnancy and the incidence of perinatal loss and miscarriage. The
      TSH cut-off value of 2.5 mIU/L identified women with higher adverse pregnancy
      outcomes.

PMID- 29453793
TI  - Cross-cultural comparison of predictors for self-care behaviors in patients with
      type 2 diabetes.
AB  - The aim of the present study was to evaluate how culture moderates the behavioral
      and psychosocial predictors of diabetes self-care activities. Patients with type
      2 diabetes were recruited in the outpatient department at two sites: Kyoto
      University hospital in Japan and the Christiana Care Health System in the USA.
      The data were collected by survey using questionnaires including questions on the
      frequency of self-care activities, behavioral and psychosocial predictors, and
      other background information from 149 Japanese patients and 48 American patients.
      The cultural impact was observed by multiple regression analyses with interaction
      terms on the association between emotional support and self-care activities in
      diet in female patients. The findings of the present study serve as an example of
      how cultural context can affect patients with diabetes, and lead to a better
      understanding of culturally sensitive behavioral intervention.

PMID- 29453794
TI  - Formulating more consistent public health policies towards cannabis and tobacco.

PMID- 29453795
TI  - Inflammatory and degenerative phases resulting from anterior cruciate rupture in
      a non-invasive murine model of post-traumatic osteoarthritis.
AB  - Joint injury is the predominant risk factor for post-traumatic osteoarthritis
      development (PTOA). Several non-invasive mouse models mimicking human PTOA
      investigate molecular mechanisms of disease development; none have characterized
      the inflammatory response to this acute traumatic injury. Our aim was to
      characterize the early inflammatory phase and later degenerative component in our
      in vivo non-invasive murine model of PTOA induced by anterior cruciate ligament
      (ACL) rupture. Right knees of 12-week-old C57Bl6 mice were placed in flexion at a
      30 degrees  offset position and subjected to a single compressive load (12N, 1.4
      mm/s) to induce ACL rupture with no obvious damage to surrounding tissues. Tissue
      was harvested 4 h post-injury and on days 3, 14, and 21; contralateral left knees
      served as controls. Histological, immunohistochemical, and gene analyzes were
      performed to evaluate inflammatory and degenerative changes. Immunohistochemistry
      revealed time-dependent expression of mature (F4/80 positive) and inflammatory
      (CD11b positive) macrophage populations within the sub-synovial infiltrate,
      developing osteophytes, and inflammation surrounding the ACL in response to
      injury. Up-regulation of genes encoding acute pro-inflammatory markers, inducible
      nitric oxide synthase, interleukin-6 and interleukin-17, and the matrix degrading
      enzymes, ADAMTS-4 and MMP3 was detected in femoral cartilage, concomitant with
      extensive cartilage damage and bone remodelling over 21-days post-injury. Our non
      invasive model describes pathologically distinct phases of the disease,
      increasing our understanding of inflammatory episodes, the tissues/cells
      producing inflammatory mediators and the early molecular changes in the joint,
      thereby defining the early phenotype of PTOA. This knowledge will guide
      appropriate interventions to delay or arrest disease progression following joint
      injury. (c) 2018 The Authors. Journal of Orthopaedic Research(r) Published by
      Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop
      Res 9999:1-10, 2018.

PMID- 29453796
TI  - Using a hospital admission survey to estimate the burden of influenza-associated
      severe acute respiratory infection in one province of Cambodia-methods used and
      lessons learned.
AB  - BACKGROUND: Understanding the burden of influenza-associated severe acute
      respiratory infection (SARI) is important for setting national influenza
      surveillance and vaccine priorities. Estimating influenza-associated SARI rates
      requires hospital-based surveillance data and a population-based denominator,
      which can be challenging to determine. OBJECTIVES: We present an application of
      the World Health Organization's recently developed manual (WHO Manual) including
      hospital admission survey (HAS) methods for estimating the burden of influenza
      associated SARI, with lessons learned to help others calculate similar estimates.
      METHODS: Using an existing SARI surveillance platform in Cambodia, we counted
      influenza-associated SARI cases during 2015 at one sentinel surveillance site in
      Svay Rieng Province. We applied WHO Manual-derived methods to count respiratory
      hospitalizations at all hospitals within the catchment area, where 95% of the
      sentinel site case-patients resided. We used HAS methods to adjust the district
      level population denominator for the sentinel site and calculated the incidence
      rate of influenza-associated SARI by dividing the number of influenza-positive
      SARI infections by the adjusted population denominator and multiplying by 100
      000. We extrapolated the rate to the provincial population to derive a case count
      for 2015. We evaluated data sources, detailed steps of implementation, and
      identified lessons learned. RESULTS: We estimated an adjusted influenza
      associated 2015 SARI rate of 13.5/100 000 persons for the catchment area of Svay
      Rieng Hospital and 77 influenza-associated SARI cases in Svay Rieng Province
      after extrapolation. CONCLUSIONS: Methods detailed in the WHO Manual and
      operationalized successfully in Cambodia can be used in other settings to
      estimate rates of influenza-associated SARI.

PMID- 29453797
TI  - Quality of partner support moderates positive affect in patients with cancer.
AB  - OBJECTIVE: In the present study, we examined whether 4 support quality-related
      characteristics moderate the impact of received partner support on positive
      affect of patients with cancer. The support quality-related characteristics were
      patients' perception regarding the willingness of their partners to offer
      support, patients' perception that partner support is certain, patients'
      satisfaction with partner relationship, and overall patients' satisfaction with
      partner support. METHODS: Seventy-seven recently diagnosed patients with cancer
      were assessed at 2 time points, during chemotherapy treatment (baseline) and 7
      months later (follow-up). Two types of received support were examined, emotional
      support and advice-guidance from partner. Multiple regression analyses were
      performed to determine the moderating effect of the quality-related variables on
      the relationship between received support at baseline and patient's positive
      affect at 7-month follow-up. RESULTS: Results showed that all 4 quality-related
      characteristics had a moderating role (f2 ranged between .06 and .16, P < .05).
      Emotional support predicted positive affect only when patients reported high
      partner willingness to offer support, considered the partner support certain,
      were satisfied with the partner relationship (a trend), and were satisfied with
      the received support. In contrast, when patients perceived their partners as
      unwilling to provide support and were dissatisfied with the relationship, support
      (both emotional and advice-guidance and advice-guidance, respectively) exhibited
      a negative impact on positive affect. CONCLUSIONS: The findings suggest that only
      when the quality of support is high does social support have a positive impact on
      patients' positive affect.

PMID- 29453798
TI  - Melatonin protects against defects induced by deoxynivalenol during mouse oocyte
      maturation.
AB  - Deoxynivalenol (DON) is one of the most prevalent fusarium mycotoxins in
      feedstuff and food. DON causes detrimental effects on human and animal
      reproductive systems by inducing oxidative stress and apoptosis. However,
      melatonin is a multifunctional endogenous hormone that plays crucial roles in the
      development of animal germ cells and embryos as a robust deoxidizer. In this
      study, we explored the effects of melatonin on the DON exposure mouse oocytes.
      Our in vitro and in vivo results showed that DON adversely affected mouse oocyte
      maturation and early embryo cleavage, while melatonin administration ameliorated
      the toxic effects of DON. DON exposure disrupted the meiotic spindle formation
      and kinetochore-microtubule attachment, which induced aneuploidy in oocytes. This
      might be through DON effects on the acetylated tubulin level. Moreover, we found
      that DON exposure caused the alteration of DNA and histone methylation level,
      which might affect early embryo cleavage. The toxic effects of DON on oocytes
      might be through its induction of oxidative stress-mediated early apoptosis,
      while the treatment with melatonin significantly ameliorated these phenotypes in
      DON-exposed mouse oocytes. Collectively, our results indicated the protection
      effects of melatonin against defects induced by DON during mouse oocyte meiotic
      maturation.

PMID- 29453799
TI  - Impact of postdiagnostic statin use on ovarian cancer mortality: A systematic
      review and meta-analysis of observational studies.
AB  - AIMS: To comprehensively evaluate the association between postdiagnostic statin
      use and mortality of ovarian cancer (OC) patients. METHODS: Using a comprehensive
      strategy, multiple databases (Medline, Embase and Web of Science) were
      systematically searched to identify observational studies that examined the
      correlation between statin use and OC mortality up to 31 December 2017. The
      studies were independently reviewed and selected based on predetermined selection
      criteria. Data were extracted independently and in duplicate. The risk of bias
      was evaluated with the Newcastle-Ottawa scale. Hazard ratios (HRs) and 95%
      confidence intervals (CIs) for mortality were summarized with a profile
      likelihood random effects model. RESULTS: Of 269 studies, eight cohort studies of
      19 904 OC patients met the inclusion criteria. Postdiagnostic statin use was
      inversely associated with all-cause mortality/overall survival (summarized HR =
      0.74; 95%CI = 0.63-0.87; I2  = 55%; n = 7) and cancer-specific mortality
      (summarized HR = 0.87; 95%CI = 0.80-0.95; I2  = 0%; n = 3) of OC patients. These
      findings were consistent by subgroup analyses stratified by study and patient
      characteristics as well as adjustments made for potential confounders. A meta
      regression analysis found no effect of modification by these variables. Of note,
      similar significant inverse effects were also observed when increasing the
      intensity (highest vs. lowest) of postdiagnostic statin use (summarized HR =
      0.84; 95%CI = 0.74-0.96; I2  = 0%; n = 3). CONCLUSION: Postdiagnostic statin use
      can improve the survival of patients with OC. Further prospective cohort and
      randomized controlled trials are warranted to confirm the therapeutic role of
      statin use on the outcome of OC.

PMID- 29453801
TI  - Regional deposition of nasal sprays in adults: A wide ranging computational
      study.
AB  - The present work examines regional deposition within the nose for nasal sprays
      over a large and wide ranging parameter space by using numerical simulation. A
      set of 7 realistic adult nasal airway geometries was defined based on computed
      tomography images. Deposition in 6 regions of each nasal airway geometry (the
      vestibule, valve, anterior turbinate, posterior turbinate, olfactory, and
      nasopharynx) was determined for varying particle diameter, spray cone angle,
      spray release direction, particle injection speed, and particle injection
      location. Penetration of nasal spray particles through the airway geometries
      represented unintended lung exposure. Penetration was found to be relatively
      insensitive to injection velocity, but highly sensitive to particle size.
      Penetration remained at or above 30% for particles exceeding 10 MUm in diameter
      for several airway geometries studied. Deposition in the turbinates, viewed as
      desirable for both local and systemic nasal drug delivery, was on average
      maximized for particles ranging from ~20 to 30 MUm in diameter, and for low to
      zero injection velocity. Similar values of particle diameter and injection
      velocity were found to maximize deposition in the olfactory region, a potential
      target for nose-to-brain drug delivery. However, olfactory deposition was highly
      variable between airway geometries, with maximum olfactory deposition ranging
      over 2 orders of magnitude between geometries. This variability is an obstacle to
      overcome if consistent dosing between subjects is to be achieved for nose-to
      brain drug delivery.

PMID- 29453800
TI  - Atomic structures of corkscrew-forming segments of SOD1 reveal varied oligomer
      conformations.
AB  - The aggregation cascade of disease-related amyloidogenic proteins, terminating in
      insoluble amyloid fibrils, involves intermediate oligomeric states. The
      structural and biochemical details of these oligomers have been largely unknown.
      Here we report crystal structures of variants of the cytotoxic oligomer-forming
      segment residues 28-38 of the ALS-linked protein, SOD1. The crystal structures
      reveal three different architectures: corkscrew oligomeric structure, nontwisting
      curved sheet structure and a steric zipper proto-filament structure. Our work
      highlights the polymorphism of the segment 28-38 of SOD1 and identifies the
      molecular features of amyloidogenic entities.

PMID- 29453802
TI  - Introduction to the special issue on membrane trafficking in neurons.

PMID- 29453803
TI  - Competition for nutrients and light: testing advances in resource competition
      with a natural phytoplankton community.
AB  - A key challenge in ecology is to understand how nutrients and light affect the
      biodiversity and community structure of phytoplankton and plant communities.
      According to resource competition models, ratios of limiting nutrients are major
      determinants of species composition. At high nutrient levels, however, species
      interactions may shift to competition for light, which might make nutrient ratios
      less relevant. The "nutrient-load hypothesis" merges these two perspectives, by
      extending the classic model of competition for two nutrients to include
      competition for light. Here, we test five key predictions of the nutrient-load
      hypothesis using multispecies competition experiments. A marine phytoplankton
      community sampled from the North Sea was inoculated in laboratory chemostats
      provided with different nitrogen (N) and phosphorus (P) loads to induce either
      single resource limitation or co-limitation of N, P, and light. Four of the five
      predictions were validated by the experiments. In particular, different resource
      limitations favored the dominance of different species. Increasing nutrient loads
      caused changes in phytoplankton species composition, even if the N:P ratio of the
      nutrient loads remained constant, by shifting the species interactions from
      competition for nutrients to competition for light. In all treatments, small
      species became dominant whereas larger species were competitively excluded,
      supporting the common view that small cell size provides a competitive advantage
      under resource-limited conditions. Contrary to expectation, all treatments led to
      coexistence of diatoms, cyanobacteria and green algae, resulting in a higher
      diversity of species than predicted by theory. Because the coexisting species
      comprised three phyla with different photosynthetic pigments, we speculate that
      niche differentiation in the light spectrum might play a role. Our results show
      that mechanistic resource competition models that integrate nutrient-based and
      light-based approaches provide an important step forward to understand and
      predict how changing nutrient loads affect community composition.

PMID- 29453805
TI  - N-Heterocyclic-Carbene-Treated Gold Surfaces in Pentacene Organic Field-Effect
      Transistors: Improved Stability and Contact at the Interface.
AB  - N-Heterocyclic carbenes (NHCs), which react with the surface of Au electrodes,
      have been successfully applied in pentacene transistors. With the application of
      NHCs, the charge-carrier mobility of pentacene transistors increased by five
      times, while the contact resistance at the pentacene-Au interface was reduced by
      85 %. Even after annealing the NHC-Au electrodes at 200  degrees C for 2 h before
      pentacene deposition, the charge-carrier mobility of the pentacene transistors
      did not decrease. The distinguished performance makes NHCs as excellent
      alternatives to thiols as metal modifiers for the application in organic field
      effect transistors (OFETs).

PMID- 29453804
TI  - Probiotics Affect One-Carbon Metabolites and Catecholamines in a Genetic Rat
      Model of Depression.
AB  - SCOPE: Probiotics may influence one-carbon (C1) metabolism, neurotransmitters,
      liver function markers, or behavior. METHODS AND RESULTS: Male adult Flinders
      Sensitive Line rats (model of depression, FSL; n = 22) received Lactobacillus
      helveticus R0052 and Bifidobacterium longum R0175 (109 or 1010 colony-forming
      units per day) or vehicle for 10 weeks. The controls, Flinders Resistant Line
      rats (FRL, n = 8), only received vehicle. C1-related metabolites were measured in
      plasma, urine, and different tissues. Monoamine concentrations were measured in
      plasma, hippocampus, and prefrontal cortex. Vehicle-treated FSL rats had higher
      plasma concentrations of betaine, choline, and dimethylglycine, but lower plasma
      homocysteine and liver S-adenosylmethionine (SAM) than FRLs. FSL rats receiving
      high-dose probiotics had lower plasma betaine and higher liver SAM compared to
      vehicle-treated FSL rats. FSLs had higher concentrations of norepinephrine,
      dopamine, and serotonin than FRLs across various brain regions. Probiotics
      decreased plasma dopamine in FSLs in a dose-dependent manner. There were no
      detectable changes in liver function markers or behavior. CONCLUSIONS: Probiotics
      reduced the flow of methyl groups via betaine, increased liver SAM, and decreased
      plasma dopamine and norepinephrine. Since these changes in methylation and
      catecholamine pathways are known to be involved in several diseases, future
      investigation of the effect of probiotics is warranted.

PMID- 29453806
TI  - CQ sensitizes human pancreatic cancer cells to gemcitabine through the lysosomal
      apoptotic pathway via reactive oxygen species.
AB  - As an established anticancer drug, gemcitabine (GEM) is an effective systemic
      treatment for advanced pancreatic cancer (PC). However, little is known about the
      potential effectors that may modify tumour cell sensitivity towards GEM.
      Autophagy, as a physiological cellular mechanism, is involved in both cell
      survival and cell death. In this study, we found that exposure to GEM induced a
      significant increase in autophagy in a dose-dependent manner in PANC-1 and BxPC-3
      cells. Inhibition of autophagy by chloroquine (CQ) and ATG7 siRNA increased GEM
      induced cytotoxicity, and CQ was more effective than ATG7 siRNA. Moreover, CQ
      significantly enhanced GEM-induced apoptosis, while ATG7 siRNA failed to show the
      similar effect. Subsequently, we identified a potential mechanism of this
      cooperative interaction by showing that GEM with CQ pretreatment markedly
      triggered reactive oxygen species (ROS) boost and then increased lysosomal
      membrane permeability. Consequently, cathepsins released from lysosome into the
      cytoplasm induced apoptosis. We showed that CQ could enhance PC cells response to
      GEM in xenograft models. In conclusion, our data showed that CQ sensitized PC
      cells to GEM through the lysosomal apoptotic pathway via ROS. Thus, CQ as a
      potential adjuvant to GEM might represent an attractive therapeutic strategy for
      PC treatment.

PMID- 29453807
TI  - Tunable poly(methacrylic acid-co-acrylamide) nanoparticles through inverse
      emulsion polymerization.
AB  - Environmentally responsive biomaterials have played key roles in the design of
      biosensors and drug delivery vehicles. Their physical response to external
      stimuli, such as temperature or pH, can transduce a signal or trigger the release
      of a drug. In this work, we designed a robust, highly tunable, pH-responsive
      nanoscale hydrogel system. We present the design and characterization of
      poly(methacrylic acid-co-acrylamide) hydrogel nanoparticles, crosslinked with
      methylenebisacrylamide, through inverse emulsion polymerization. The effects of
      polymerization parameters (i.e., identities and concentrations of monomer and
      surfactant) and polymer composition (i.e., weight fraction of ionic and
      crosslinking monomers) on the nanoparticles' bulk and environmentally responsive
      properties were determined. We generated uniform, spherical nanoparticles which,
      through modulation of crosslinking, exhibit a volume swelling of 1.77-4.07,
      relative to the collapsed state in an acidic environment. We believe our system
      has potential as a base platform for the targeted, injectable delivery of
      hydrophilic therapeutics. With equal importance, however, we hope that our
      systematic analysis of the individual impacts of polymerization and purification
      conditions on nanoparticle composition, morphology, and performance can be used
      to expedite the development of alternate hydrophilic nanomaterials for a range of
      biomedical applications. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part
      A: 106A: 1677-1686, 2018.

PMID- 29453809
TI  - Treatment optimization with secukinumab 150 mg for moderate-to-severe psoriasis
      in clinical practice: a single-center open-label 52-week study.

PMID- 29453808
TI  - Three-dimensional printing in congenital heart disease: A systematic review.
AB  - Three-dimensional (3D) printing has shown great promise in medicine with
      increasing reports in congenital heart disease (CHD). This systematic review aims
      to analyse the main clinical applications and accuracy of 3D printing in CHD, as
      well as to provide an overview of the software tools, time and costs associated
      with the generation of 3D printed heart models. A search of different databases
      was conducted to identify studies investigating the application of 3D printing in
      CHD. Studies based on patient's medical imaging datasets were included for
      analysis, while reports on in vitro phantom or review articles were excluded from
      the analysis. A total of 28 studies met selection criteria for inclusion in the
      review. More than half of the studies were based on isolated case reports with
      inclusion of 1-12 cases (61%), while 10 studies (36%) focused on the survey of
      opinion on the usefulness of 3D printing by healthcare professionals, patients,
      parents of patients and medical students, and the remaining one involved a
      multicentre study about the clinical value of 3D printed models in surgical
      planning of CHD. The analysis shows that patient-specific 3D printed models
      accurately replicate complex cardiac anatomy, improve understanding and knowledge
      about congenital heart diseases and demonstrate value in preoperative planning
      and simulation of cardiac or interventional procedures, assist surgical decision
      making and intra-operative orientation, and improve patient-doctor communication
      and medical education. The cost of 3D printing ranges from USD 55 to USD 810.
      This systematic review shows the usefulness of 3D printed models in congenital
      heart disease with applications ranging from accurate replication of complex
      cardiac anatomy and pathology to medical education, preoperative planning and
      simulation. The additional cost and time required to manufacture the 3D printed
      models represent the limitations which need to be addressed in future studies.

PMID- 29453810
TI  - A case-control study and meta-analysis reveal the association between COX-2 G
      765C polymorphism and primary end-stage hip and knee osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is a popular arthrosis featured as pain, limited
      joint activity, and deformity. Cyclooxygenase-2 (COX-2) has been reported to be
      up-regulated in arthritic tissues and is integral to the progression of
      osteoarthritis (OA). Previous studies showed the COX-2 promoter G-765C
      polymorphism could influence COX-2 expression. However, the relationship between
      the variant and OA risk is contrasting. METHODS: We conducted a case-control
      study with 196 primary end-stage hip and knee OA cases and 196 controls in a
      Chinese Han population. Subsequently, we integrated this case-control study in a
      meta-analysis to acquire greater statistical power. The results from our case
      control study using MassARRAY genotyping technology and binary logistic
      regression statistical methods. RESULTS: The variant carriers in the Chinese Han
      population had a lower primary end-stage hip and knee OA susceptibility (C vs G:
      OR = 0.350, 95%CI: 0.154-0.797, P = .012; GC vs GG: adjusted OR = 0.282, 95%CI:
      0.118-0.676, P = .005). Stratification studies indicated that a higher GC
      frequency in women decreased not only knee OA susceptibility but also unilateral
      knee OA risk. The meta-analysis showed that the variant exhibited a significantly
      decreased OA risk through comparisons involving allelic, homozygous,
      heterozygous, and dominant models. CONCLUSION: Our findings suggest that the COX
      2 G-765C polymorphism exerts a protective effect against primary end-stage knee
      osteoarthritis in a female Chinese Han population.

PMID- 29453811
TI  - Multimodal treatment including tandem high-dose chemotherapy and autologous stem
      cell transplantation in children with anaplastic ependymomas.
AB  - In this study, we evaluated the results of multimodal treatment that included
      tandem HDCT/auto-SCT in children with anaplastic ependymomas. Fourteen patients
      with anaplastic ependymomas were enrolled from 2006 to 2014. Six cycles of
      induction chemotherapy were administered to all patients before they underwent
      tandem HDCT/auto-SCT. Patients who were older than 3 years of age were
      administered RT after two cycles of induction chemotherapy. In patients under 3
      years of age, RT was either omitted or delayed until they reached 3 years of age,
      if the patients experienced CR after tandem HDCT/auto-SCT. All patients,
      including two who experienced disease progression during induction treatment,
      underwent the first HDCT/auto-SCT, and 13 subsequently underwent the second
      HDCT/auto-SCT. One patient died from hepatic VOD during the second HDCT/auto-SCT;
      other toxicities occurring during tandem HDCT/auto-SCT were manageable. Relapses
      or progression occurred in seven patients, and five of seven of them remain alive
      till date after salvage treatment, including surgery and RT. The 5-year overall
      and event-free survival rates were 85.1% +/- 9.7% and 50.0% +/- 13.4%,
      respectively. These findings suggest that multimodal treatment including tandem
      HDCT/auto-SCT could be a feasible option for improving survival in children with
      anaplastic ependymomas.

PMID- 29453812
TI  - Cognitive outcomes in children and adolescents born very preterm: a meta
      analysis.
AB  - AIM: To estimate the association between very preterm birth (<32wks' gestation)
      and intelligence, executive functioning, and processing speed throughout
      childhood and adolescence, and to examine the effects of gestational age,
      birthweight, and age at assessment. METHOD: Studies were included if children
      were born at earlier than 32 weeks' gestation, aged 4 to 17 years, had an age
      matched term control group, and if the studies used standardized measures, were
      published in an English-language peer-reviewed journal, and placed no
      restrictions on participants based on task performance. RESULTS: We evaluated
      6163 children born very preterm and 5471 term-born controls from 60 studies.
      Children born very preterm scored 0.82 SDs (95% confidence interval [CI] 0.74
      0.90; p<0.001) lower on intelligence tests, 0.51 SDs (95% CI 0.44-0.58; p<0.001)
      lower on measures of executive functioning, and 0.49 SDs (95% CI 0.39-0.60;
      p<0.001) lower on measures of processing speed than term-born controls.
      Gestational age and birthweight were associated with study effect size in
      intelligence and executive functioning of younger children only. Age at
      assessment was not associated with study effect size. INTERPRETATION: Children
      born very preterm have medium to large deficits in these cognitive domains. WHAT
      THIS PAPER ADDS: This meta-analysis is centred on very preterm birth and three
      cognitive domains. The three critical cognitive domains are intelligence,
      executive functioning, and processing speed.

PMID- 29453813
TI  - Association between two common transitions of H2BFWT gene and male infertility: a
      case-control, meta, and structural analysis.
AB  - H2BFWT is one of the testis-specific histones that plays a fundamental role in
      spermatogenesis, and single nucleotide polymorphisms (SNPs) in this gene may
      result in male infertility. This study aimed to investigate the association
      between -9C>T and 368A>G transitions of H2BFWT gene and male infertility through
      a case-control, meta-analysis, and a bioinformatics approach. In this case
      control study, 490 subjects including 240 idiopathic infertile men and 250
      healthy controls were included. The -9C>T and 368A>G SNPs genotyping were
      performed by a PCR-RFLP method. To find eligible studies for meta-analysis, we
      searched valid scientific databases. The odds ratios with 95% confidence
      intervals were estimated to find the strength of these associations. Furthermore,
      the influences of two common transitions on the molecular features of H2BFWT were
      assessed by in silico tools. Our case-control data revealed that -9C>T is not
      associated with male infertility. But, there was a significant association
      between 368A>G and male infertility. In the meta-analysis, five eligible studies
      were included. Our data revealed significant associations between -9C>T, 368A>G,
      and male infertility in overall and stratified analyses. Moreover, structural
      analysis showed that 368A>G could affect the protein structure (SNAP prediction:
      non-neutral, score: 42, expected accuracy: 71%; SIFT prediction: deleterious,
      score: -2.55), while -9C>T may affect the binding nucleotide in the promoter
      region. Based on these findings, two aforementioned polymorphisms were associated
      with increased risk of male infertility. However, studies with larger sample size
      and different ethnicities are needed to obtain more accurate conclusions.

PMID- 29453814
TI  - Preclinical evaluation of a semi-automated and rapid commercial electrophoresis
      assay for von Willebrand factor multimers.
AB  - BACKGROUND: The von Willebrand factor (VWF) multimer test is required to
      correctly subtype qualitative type 2 von Willebrand disease (VWD). The current
      VWF multimer assays are difficult, nonstandardized, and time-consuming. The
      purpose of this study was to evaluate the clinical utility of the commercial VWF
      multimer kit by Sebia (Lisses, France), an electrophoresis technique yielding
      same-day results. METHODS: Ten healthy volunteer plasma samples, in-house
      reference plasma (IRP) and commercial normal plasma (CNP) samples, 10 plasma
      samples from patients with a known VWD type, 1 hemophilia A plasma sample, and 7
      external quality assurance (EQA) samples were analyzed using the commercial VWF
      multimer kit. Additional coagulation testing included measurements of VWF antigen
      (VWF:Ag), VWF activity (VWF:Ac), and FVIII activity (FVIII:C). RESULTS: The CNP
      results revealed a relative loss of the highest molecular weight multimers;
      therefore, IRP was preferred as the reference sample. The interpretations of 10
      patients with a known VWD type could be successfully reproduced and agreed with
      previous VWF multimer results. In all EQA surveys, the multimer results and final
      VWD diagnosis agreed with expert opinion. CONCLUSIONS: The VWF multimer assay by
      Sebia is easy to perform and can be successfully implemented in any clinical
      laboratory for second-stage evaluation of VWD. The resolution power of multimer
      distribution is adequate to correctly classify VWD types 1, 2A, 2B, and 3.

PMID- 29453815
TI  - Chitosan porous 3D scaffolds embedded with resolvin D1 to improve in vivo bone
      healing.
AB  - The aim of this study was to investigate the effect chitosan (Ch) porous 3D
      scaffolds embedded with resolvin D1 (RvD1), an endogenous pro-resolving lipid
      mediator, on bone tissue healing. These scaffolds previous developed by us have
      demonstrated to have immunomodulatory properties namely in the modulation of the
      macrophage inflammatory phenotypic profile in an in vivo model of inflammation.
      Herein, results obtained in an in vivo rat femoral defect model demonstrated that
      two months after Ch + RvD1 scaffolds implantation, an increase in new bone
      formation, in bone trabecular thickness, and in collagen type I and Coll I/Coll
      III ratio were observed. These results suggest that Ch scaffolds embedded with
      RvD1 were able to lead to the formation of new bone with improvement of
      trabecular thickness. This study shows that the presence of RvD1 in the acute
      phase of the inflammatory response to the implanted biomaterial had a positive
      role in the subsequent bone tissue repair, thus demonstrating the importance of
      innovative approaches for the control of immune responses to biomedical implants
      in the design of advanced strategies for regenerative medicine. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1626-1633, 2018.

PMID- 29453816
TI  - Lewis Acid Catalyzed Stereoselective Dearomative Coupling of Indolylboron Ate
      Complexes with Donor-Acceptor Cyclopropanes and Alkyl Halides.
AB  - Indolylboron ate complexes readily generated from 2-lithioindoles and boronic
      esters underwent multicomponent dearomative coupling with D-A cyclopropanes and
      alkyl halides in the presence of Sc(OTf)3 as a catalyst. The reactions proceeded
      with complete diastereoselectivity and excellent stereospecificity to provide
      indolines containing three contiguous stereocenters. The valuable boronic ester
      moiety remains in the product and allows for subsequent functionalization.

PMID- 29453817
TI  - Endocrine and psychological aspects of sexual dysfunction in Klinefelter
      patients.
AB  - Klinefelter syndrome is a frequent cause of hypogonadism, but despite hundreds of
      publications on different aspects of Klinefelter syndrome, only a few studies
      dealt with sexual dysfunction. In particular, testosterone is critical for
      various aspects of sexual response, but its role on sexuality in Klinefelter
      syndrome patients is debatable and no studies have evaluated the efficacy of
      testosterone treatment on sexual dysfunction in these subjects. Furthermore, the
      impact of psychological and relational aspects on sexual function of Klinefelter
      syndrome subjects is poorly defined. In this study, we aimed to determine the
      presence and type of sexual dysfunctions in Klinefelter syndrome subjects; to
      correlate them with testosterone levels and psychosexological and relational
      domains; and to evaluate the effects of testosterone therapy. We studied 62 non
      mosaic naive Klinefelter syndrome patients and 60 age-matched controls by means
      of medical history, psychosexological history, 15-item International Index of
      Erectile Function questionnaire, endocrine assessment, and dynamic penile color
      Doppler ultrasound. Twenty-five hypogonadal Klinefelter syndrome patients were
      studied after 6 months of testosterone replacement therapy. Klinefelter syndrome
      subjects have reduced 15-item International Index of Erectile Function scores
      regarding sexual desire, intercourse satisfaction, and overall satisfaction with
      respect to controls, and these aspects were significantly associated with
      testosterone levels. Klinefelter syndrome subjects had also higher prevalence of
      erectile dysfunction, but no relation with testosterone levels was evident. A
      high prevalence of a range of psychological disturbances was present in
      Klinefelter syndrome subjects with erectile dysfunction with respect to those
      without erectile dysfunction. No statistical difference in the prevalence of
      premature and delayed ejaculation was observed between Klinefelter syndrome and
      control subjects. Testosterone replacement therapy improved sexual desire,
      intercourse satisfaction, and overall satisfaction scores, but had no effect on
      erectile function. Penile color Doppler ultrasound was normal in all subjects.
      This study shows that sexual dysfunction in Klinefelter syndrome is
      multifactorial and related only in part to hypogonadism and largely to
      psychological disturbances. Evaluation and therapy of sexual dysfunction should
      include a combined andrological and psychosexological approach.

PMID- 29453819
TI  - Regulatory T cells, natural killer cells, and obesity in patients with
      gestational diabetes mellitus.

PMID- 29453818
TI  - The association between thyroid function and incidence of metabolic syndrome in
      euthyroid subjects: Tianjin chronic low-grade systemic inflammation and health
      cohort study.
AB  - OBJECTIVE: Thyroid hormones (THs) are primarily responsible for the regulation of
      energy homeostasis and metabolism. However, few prospective studies have assessed
      the association between THs and metabolic syndrome (MetS) in a general
      population. We therefore designed a cohort study to examine whether serum TH
      levels within the reference range are predictive factors for developing MetS in
      adults. DESIGN: Prospective cohort study. PARTICIPANTS: A prospective study (n =
      6119) was performed in Tianjin, China. Participants without a history of MetS
      were followed up for 1 to 3 years with a median follow-up duration of 2 years.
      MEASUREMENTS: Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid
      stimulating hormone (TSH) levels were measured by chemiluminescence immunoassay.
      MetS was defined in accordance with the criteria of the American Heart
      Association scientific statements of 2009. THs, TSH levels and MetS were assessed
      yearly during the follow-up. Adjusted Cox proportional hazards regression models
      were used to assess the associations between FT3, FT4 and TSH quintiles and MetS.
      RESULTS: The incidence of MetS was 17.7% (96 per 1000 person-years). In the final
      multivariate models, the hazard ratios (95% confidence interval) for MetS across
      serum FT3 quintiles were 1.00 (reference), 1.03 (0.84, 1.25), 1.14 (0.94, 1.38),
      1.09 (0.90, 1.32) and 1.33 (1.11, 1.61), respectively (P for trend <.01).
      However, no significant associations between FT4, TSH and MetS were observed.
      CONCLUSIONS: This population-based prospective cohort study suggests that
      increased serum FT3 level, rather than FT4 and TSH, is an independent predictor
      for developing MetS in euthyroid subjects.

PMID- 29453820
TI  - Observations on the measurement of zinc protoporphyrin in both whole blood and
      washed red cells in young children.

PMID- 29453821
TI  - Trends and predictors of cesarean birth in Singapore, 2005-2014: A population
      based cohort study.
AB  - BACKGROUND: Rates of cesarean birth have continued to rise in many high-income
      countries. We examined the temporal trends and predictors of cesarean birth in
      Singapore. METHODS: Linked hospitalization and Birth Registry data were used to
      examine all live births to Singaporean citizens and permanent residents between
      January 1, 2005 and December 31, 2014 (n = 342 932 births). We calculated
      cesarean rates and age-adjusted average annual percent change (AAPC) in those
      rates and used sequential multivariable regression modeling to assess the
      contribution of changes in predictors to the change in cesarean rates over time.
      RESULTS: The overall cesarean rate in Singapore rose from 32.2% in 2005 to 37.4%
      in 2014. Among singleton, cephalic, term pregnancies, the two major predictions
      of cesarean were nulliparity and previous cesarean, each accounting for just over
      one-third of all cesareans. Higher AAPC was observed in nulliparous women of
      Indian ethnicity (0.74% [95% confidence interval 0.68-0.80]) compared with
      Chinese (0.62% [0.60-0.65]) or Malay women (0.63% [0.59-0.68]), and in women who
      delivered in private hospitals (0.62% [0.60-0.64]) compared with those delivered
      under subsidized care in public hospitals (0.58% [0.52-0.63]). Parity and
      education had the largest influences on cesarean birth trend (attenuation of AAPC
      from 0.62% [0.59-0.66] to 0.39% [0.38-0.40] after adjustment). CONCLUSION:
      Cesarean birth has continued to rise at a steady rate in Singapore. Strategies to
      curb this temporal increase include avoidance of medically unnecessary primary
      cesarean and attempts at trial of labor and vaginal delivery among women with a
      history of prior cesarean.

PMID- 29453822
TI  - Full-genome sequencing of porcine circovirus 3 field strains from Denmark, Italy
      and Spain demonstrates a high within-Europe genetic heterogeneity.
AB  - Porcine circovirus 3 (PCV3) is a new species of the Circovirus genus, which has
      recently been associated with different clinical syndromes. Its presence has been
      reported in different countries of North and South America, Asia and recently
      also Europe (Poland). However, different from the other continents, no European
      PCV3 sequence is currently available in public databases. There is a strong need
      of epidemiological data and full-genome sequences from Europe because of its
      relevance in the understanding of PCV3 molecular epidemiology and control. To
      fill this lack of information, samples collected in Denmark, Italy and Spain in
      2016 and 2017 were screened for PCV3. Of the Danish samples, 36 of 38 the lymph
      nodes, six of 20 serum samples and two of 20 lung samples tested positive.
      Similarly, 10 of 29 lungs, 20 of 29 organ pools, six of 33 sera and one of eight
      nasal swabs tested PCV3 positive in Italy. Fourteen of 94 serum pools from seven
      of 14 Spanish farms were also positive. Despite the convenience nature of the
      sampling prevents any precise prevalence estimation, the preliminary screening of
      the data from three European countries confirmed a rather wide PCV3 distribution
      in Europe. Furthermore, the analysis of the six obtained complete European PCV3
      genomes and their comparison with the public available sequences seems to support
      a remarkable worldwide PCV3 circulation. These results underline once more the
      urgency of more extensive epidemiological studies to refine the current knowledge
      on PCV3 evolution, transmission, spreading patterns and impact on pig health.

PMID- 29453823
TI  - Paeoniflorin ameliorates collagen-induced arthritis via suppressing nuclear
      factor-kappaB signalling pathway in osteoclast differentiation.
AB  - Paeoniflorin (PF), extracted from the root of Paeonia lactiflora Pall, exhibits
      anti-inflammatory properties in several autoimmune diseases. Osteoclast, the only
      somatic cell with bone resorbing capacity, was the direct cause of bone
      destruction in rheumatoid arthritis (RA) and its mouse model, collagen-induced
      arthritis (CIA). The objective of this study was to estimate the effect of PF on
      CIA mice, and explore the mechanism of PF in bone destruction. We demonstrated
      that PF treatment significantly ameliorated CIA through inflammatory response
      inhibition and bone destruction suppression. Furthermore, PF treatment markedly
      decreased osteoclast number through the altered RANKL/RANK/OPG ratio and
      inflammatory cytokines profile. Consistently, we found that osteoclast
      differentiation was significantly inhibited by PF through down-regulation of
      nuclear factor-kappaB activation in vitro. Moreover, we found that PF suppressed
      nuclear factor-kappaB activation by decreasing its translocation to the nucleus
      in osteoclast precursor cells. Taken together, our new findings provide insights
      into a novel function of PF in osteoclastogenesis and demonstrate that PF would
      be a new therapeutic modality as a natural agent for RA treatment and other
      autoimmune conditions with bone erosion.

PMID- 29453824
TI  - Giving in when feeling less good: Procrastination, action control, and social
      temptations.
AB  - Emotion-regulation perspectives on procrastination highlighting the primacy of
      short-term mood regulation focus mainly on negative affect. Positive affect,
      however, has received much less attention and has not been considered with
      respect to social temptations. To address this issue, we examined how trait
      procrastination was linked to positive and negative affect in the context of
      social temptations across two prospective studies. Action Control Theory,
      Personality Systems Interactions Theory, and a mood regulation theory of
      procrastination served as guiding conceptual frameworks. In Study 1, moderated
      mediation analyses revealed that low positive affect explained the link between
      trait procrastination and time spent procrastinating on academic tasks over a 48
      hr period in a student sample (N = 142), and this effect was moderated by the
      presence of social temptations. Parallel results for goal enjoyment assessed at
      Time 2 were found in Study 2 with a community sample (N = 94) attempting to make
      intended health behaviour changes over a 6-month period. Our findings indicate
      that procrastinators are at risk for disengaging from intended tasks when social
      temptations are present and positive task-related affect is low.

PMID- 29453825
TI  - Iatrogenic hepatic portal venous gas following balloon endoscopy in a patient
      with hepaticojejunostomy stricture.

PMID- 29453827
TI  - Using niche breadth theory to explain generalization in mutualisms.
AB  - For a mutualism to remain evolutionarily stable, theory predicts that mutualists
      should limit their associations to high-quality partners. However, most
      mutualists either simultaneously or sequentially associate with multiple partners
      that confer the same type of reward. By viewing mutualisms through the lens of
      niche breadth evolution, we outline how the environment shapes partner
      availability and relative quality, and ultimately a focal mutualist's partner
      breadth. We argue that mutualists that associate with multiple partners may have
      a selective advantage compared to specialists for many reasons, including
      sampling, complementarity, and portfolio effects, as well as the possibility that
      broad partner breadth increases breadth along other niche axes. Furthermore,
      selection for narrow partner breadth is unlikely to be strong when the
      environment erodes variation in partner quality, reduces the costs of interacting
      with low-quality partners, spatially structures partner communities, or decreases
      the strength of mutualism. Thus, we should not be surprised that most mutualists
      have broad partner breadth, even if it allows for ineffective partners to
      persist.

PMID- 29453828
TI  - Clinical and aesthetic outcomes of immediately placed single-tooth implants with
      immediate vs. delayed restoration in the anterior maxilla: A retrospective cohort
      study.
AB  - OBJECTIVE: To evaluate the impact of the timing of restoration on clinical and
      aesthetic outcomes following immediate implant placement in the maxillary
      aesthetic zone. MATERIAL AND METHODS: Forty patients (16 males, 24 females) with
      a mean age of 50.55 +/- 12.79 years (range 19-74) who had a single maxillary
      anterior tooth replaced by an immediate implant were included in this study.
      Twenty patients had their implant restored immediately with a provisional
      restoration (Group A), while the other 20 patients had a delayed restoration
      placed after 3-4 months of non-submerged healing (Group B). Clinical parameters
      and hard-tissue changes were evaluated after a mean follow-up period of 3 years.
      Aesthetic evaluation was carried out using the Pink Esthetic Score (PES) and the
      White Esthetic Score (WES). RESULTS: No significant differences were observed in
      the bone level changes between the two groups: 0.05 +/- 0.65 mm mesially and 0.06
      +/- 0.52 mm distally for the immediate group and 0.30 +/- 0.54 mm mesially and
      0.21 +/- 0.60 mm distally for the delayed group, respectively. The median PES
      scores were 11.5 for Group A and 10 for Group B. Mean PES and WES scores did not
      differ significantly between Groups A and B: PES (11.1 vs. 10.3; p = .16) and WES
      (8.4 vs. 7.8; p = .16). In terms of individual PES variables, the distal papillae
      were significantly better in Group A as compared to Group B (p = .006).
      CONCLUSIONS: Within the limits of this study, timing of restoration seemed to
      positively affect the aesthetic outcomes of immediately placed implants as
      evidenced by higher median PES values for the immediate restoration group when
      compared to the delayed restoration group. Restoration timing had no impact on
      the individual PES variables, except for the distal papillary height which was
      superior in the immediate restoration group.

PMID- 29453826
TI  - Protein Turnover in Aging and Longevity.
AB  - Progressive loss of proteostasis is a hallmark of aging that is marked by
      declines in various components of proteostasis machinery, including: autophagy,
      ubiquitin-mediated degradation, protein synthesis, and others. While declines in
      proteostasis have historically been observed as changes in these processes, or as
      bulk changes in the proteome, recent advances in proteomic methodologies have
      enabled the comprehensive measurement of turnover directly at the level of
      individual proteins in vivo. These methods, which utilize a combination of stable
      isotope labeling, mass spectrometry, and specialized software analysis, have now
      been applied to various studies of aging and longevity. Here we review the role
      of proteostasis in aging and longevity, with a focus on the proteomic methods
      available to conduct protein turnover in aging models and the insights these
      studies have provided thus far.

PMID- 29453829
TI  - Proposal for new selection criteria considering pre-transplant muscularity and
      visceral adiposity in living donor liver transplantation.
AB  - BACKGROUND: The significance of pre-operative body composition has recently
      attracted much attention in various diseases. However, cut-off values for these
      parameters remain undetermined, and these factors are not currently included in
      selection criteria for recipients of living donor liver transplantation (LDLT).
      METHODS: Using computed tomography of 657 donors for LDLT, skeletal muscle mass,
      muscle quality, and visceral adiposity were evaluated by using skeletal muscle
      mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to
      subcutaneous adipose tissue area ratio (VSR). Sex-specific cut-offs for SMI,
      IMAC, and VSR were determined, and correlations with outcomes after LDLT in 277
      recipients were examined with the aim of establishing new selection criteria for
      LDLT. RESULTS: On the basis of younger donor data, we determined sex-specific cut
      off values for low SMI, high IMAC, and high VSR (mean +/- 2 standard deviations).
      Patients with all three factors showed the lowest survival rate after LDLT (1
      year survival rate, 41.2%; P < 0.001). On multivariate analysis, low SMI (P =
      0.002), high IMAC (P = 0.002), and high VSR (P = 0.001) were identified as
      independent risk factors for mortality after LDLT. Based on these findings, we
      have excluded patients showing all three factors (low SMI, high IMAC, and high
      VSR) as candidates for LDLT since October 2016. CONCLUSIONS: Using cut-off values
      determined from healthy donors, we have established new selection criteria for
      LDLT including body composition, which should improve post-transplant outcomes.

PMID- 29453830
TI  - Eosinophilic polymorphic and pruritic eruption associated with radiotherapy in a
      patient with primary nodal Merkel cell carcinoma.

PMID- 29453831
TI  - Evaluation of a recombinant multiepitope antigen for diagnosis of hepatitis C
      virus: A lower cost alternative for antigen production.
AB  - BACKGROUND: The most of the hepatitis C-infected patients remain undiagnosed
      until they develop severe liver damage or submitted for serological screening.
      OBJECTIVE: To evaluate a recombinant multiepitope protein for detection of IgG
      anti-hepatitis C virus. METHOD: A synthetic gene was cloned, expressed in
      Escherichia coli, and the recombinant protein was purified. Human serum panel
      consisted of 88 positives (20 HCV genotyped) and 376 negatives for hepatitis C, 6
      positives for human acquired immunodeficiency virus, 6 syphilis positives, 6
      hepatitis B positives were tested by IgG antihepatitis C virus using the protein
      by enzyme-linked immunosorbent assay. In addition, 20 positive (all genotyped
      samples) and 20 negative samples were also tested by immunoblot and dot blot
      assays. RESULTS: Positive hepatitis C sera were strongly reactive against the
      protein by immunoblot assay. In the dot blot assay, positive sera were reactive
      until 1:1000 dilution and there were no false positive results in the hepatitis C
      negative sera. In the enzyme-linked immunosorbent assay, positive and negative
      sera had significant discrimination. No cross-reaction was observed in samples
      positive for syphilis; human acquired immunodeficiency virus and hepatitis B. All
      20 genotyped samples were positive by the three methods. CONCLUSION: The
      multiepitope protein used here has a lower cost compared to production of each
      antigen separately and could be an alternative for the serological diagnosis of
      hepatitis C.

PMID- 29453832
TI  - Living-donor liver transplantation for mild Zellweger spectrum disorder: Up to 17
      years follow-up.
AB  - Mild Zellweger spectrum disorder, also described as Infantile Refsum disease, is
      attributable to mutations in PEX genes. Its clinical course is characterized by
      progressive hearing and vision loss, and neurodevelopmental regression.
      Supportive management is currently considered the standard of care, as no
      treatment has shown clinical benefits. LT was shown to correct levels of
      circulating toxic metabolites, partly responsible for chronic neurological
      impairment. Of three patients having undergone LT for mild ZSD, one died after
      LT, while the other two displayed significant neurodevelopmental improvement on
      both the long-term (17 years post-LT) and short-term (9 months post-LT) follow
      up. We documented a sustained improvement of biochemical functions, with a
      complete normalization of plasma phytanic, pristanic, and pipecolic acid levels.
      This was associated with stabilization of hearing and visual functions, and
      improved neurodevelopmental status, which has enabled the older patient to lead a
      relatively autonomous lifestyle on the long term. The psychomotor acquisitions
      have been markedly improved as compared to their affected siblings, who did not
      undergo LT and exhibited a poor neurological outcome with severe disabilities. We
      speculate that LT performed before the onset of severe sensorineural defects in
      mild ZSD enables partial metabolic remission and improved long-term clinical
      outcomes.

PMID- 29453833
TI  - Ketamine induces apoptosis in lung adenocarcinoma cells by regulating the
      expression of CD69.
AB  - Ketamine, an anesthetic, analgesic, or sedative, is widely used for the treatment
      of cancer pain. Recently, ketamine has been also reported to be tumor repressor
      for inhibiting proliferation, invasion, and migration, and inducing apoptosis in
      many cancers. However, whether ketamine can induce the apoptosis of lung
      adenocarcinoma (LUAD) and which downstream molecular mediates its function remain
      largely unknown. A LUAD cell line A549 was incubated with ketamine at 0, 1, 10,
      and 100 MUmol/L for 24 h. Trypan blue staining was used to detect the cell
      viability. Flow cytometry (FACS) was applied to evaluate cell apoptosis
      proportion. The expression of CD69 was quantitated by western blotting. Ketamine
      induced the A549 cell apoptosis in a concentration-dependent manner. CD69 was
      downregulated in LUAD patients' cancer tissue compared with the normal tissue.
      CD69 can be upregulated in ketamine treating A549 cells and induce the A549 cell
      apoptosis. Rescue experiment showed that downregulation of CD69 significantly
      blocked the function of ketamine on inducing apoptosis. Taken together, our
      results demonstrated that ketamine induced LUAD cells apoptosis by upregulating
      the CD69 expression. This study suggests that the ketamine can be potential drug
      for LUAD treatment, and the ketamine/CD69 signaling may be the new potential
      therapeutic target LUAD therapy.

PMID- 29453834
TI  - Demystifying Evidence-Based Policy Analysis by Revealing Hidden Value-Laden
      Constraints.
AB  - Consider any choice that affects some social policy. A decision that considers
      evidence will, at its heart, contain some kind of explicit or implicit "because"
      statement: "We are doing X because the evidence says Y." But can evidence ever
      truly speak for itself, in the sense of being reducible to objective utterances
      that are either correct or in need of correction? Before answering, consider what
      you'd prefer. Would you rather receive evidence that was free of any value
      judgments imposed by human actors, that was laden with value judgments that you
      agree with, or laden with value judgments that you disagree with? The central
      assertion of this essay is that, throughout policy analysis but especially in
      assessments of the costs and benefits of regulating versus encouraging new
      technologies (cost-benefit analysis, or CBA), the first possibility above is a
      mirage, and the second and third are self-contradictory. Instead, we are
      overwhelmingly confronted with a fourth possibility: we receive evidence that
      appears to be (or is deliberately touted as) value neutral but is suffused with
      hidden value judgments. In the second part of this essay, entitled "A Guided Tour
      through Inevitable Value Judgments," I identify in a systematic way approximately
      sixty-five value judgments that are routinely (in some cases, invariably) made in
      CBA, but that are kept hidden. For each judgment, I discuss its genesis as it is
      most commonly invoked in CBA, explain how it is hidden in plain sight, and offer
      one or more value judgments that could be made instead of or in addition to the
      conventional one. The alternative judgments highlight the width of the spectrum
      of reasonable conclusions an analyst could reach merely by substituting other
      judgments for the ones currently embedded. Bringing hidden value judgments to
      light is doubly valuable. First, it allows discussion to ensue on a level playing
      field; instead of conclusory statements about what the evidence says,
      transparency permits statements taking the form of "when channeled through these
      value judgments, the evidence says this." Perhaps more importantly, transparency
      about value judgments permits participants in the discussions to offer
      interpretations of evidence contingent on there being different value judgments
      chosen at one or more points in the analysis, interpretations that may suggest
      that alternative course(s) of action are preferable to the one being championed.

PMID- 29453835
TI  - Lessons from Environmental Regulation.
AB  - Much of the most substantive and in-depth experience with formal cost-benefit
      analysis in the public policy realm has occurred in the context of federal
      environmental regulation in the United States. This experience has many important
      lessons to teach in the realm of synthetic biology. Indeed, many of the dangers
      and pitfalls that arise when decision-makers use formal CBA to evaluate
      environmental regulation seem likely to arise in the synthetic biology context as
      well, sometimes in particularly troubling forms. Unfortunately, while in many
      instances these concerns may well point toward a rejection of formal CBA for
      synthetic biology, the experience from environmental regulation turns out to be
      far less helpful in identifying alternative decision-making tools. Because the
      decisions that arise in the synthetic biology context have a fundamentally
      different structure from decisions about environmental regulation, the most
      useful alternatives from that context do not map easily onto this new context. It
      may well be generally true that in the search for decision-making tools, we
      should not be looking for a single silver bullet that will work in all public
      policy realms. Perhaps, instead, different kinds of decision-making call for
      different tools. This may be true even within the realm of synthetic biology. I
      am not entirely sure what the "right" tool is for synthetic biology applications,
      or even whether a "right" tool exists. But at the end of this essay, I offer a
      few tentative thoughts about why scenario analysis-a strategic planning tool
      first developed in the context of military planning following World War II-might
      be one alternative worth considering.

PMID- 29453836
TI  - CBA and Precaution: Policy-Making about Emerging Technologies.
AB  - In the technology assessment literature, the leading alternative to CBA-like
      methods is usually held to be precaution, which is understood in various ways but
      is always about making decisions under conditions of uncertainty. Under such
      conditions, proponents of precaution commonly hold, a straightforward tallying of
      potential outcomes does not seem possible. Since CBA aims to tally up outcomes to
      determine which outcome would produce the greatest public benefit, precaution
      begins to look like, not just an alternative to CBA, but an incompatible
      alternative. Nonetheless, some of the better-known formulations of a
      precautionary principle expressly call for combining precaution with assessment
      of costs and benefits. This essay examines the possible intersection of
      precaution and CBA. It argues that a moderate kind of CBA is a necessary part of
      a moderate kind of precaution. The existing proposals for integrating CBA and
      precaution start with an assumption that the integrative task consists in
      combining decision tools that generate (contrasting) substantive guidance. An
      alternative approach, explored here, starts with the idea that precaution is not
      a decision-generating tool. Rather, it is a way of organizing the thinking that
      leads eventually to substantive conclusions. The appropriate policy response is
      reached not by applying a principle but by studying the situation-the proposed
      action and the problem it is meant to address-and developing recommendations
      tailored to it. What makes the thinking precautionary is that it emphasizes
      certain questions-about risk, uncertainty, and values-that CBA tends to suppress.
      So understood, precaution may well slow the science but is not intrinsically
      opposed to science or innovation. It can be understood, in fact, as continuous
      with the science because the contextual understanding of the science and the
      problems it is meant to address would emerge-in part-from a close engagement with
      the science.

PMID- 29453837
TI  - Benefit-Cost Analysis and Emerging Technologies.
AB  - Emerging technologies are, by definition, full of surprises: developments that we
      cannot fully anticipate and that might have some bad outcomes as well as good
      ones. This presents a challenge for anyone trying to make forward-looking policy
      decisions, including those who apply benefit-cost analysis. BCA is now widely
      known and used, but it is also widely misunderstood-by many of its advocates as
      well as its detractors. In this essay, I will begin by examining some of the
      strengths and weaknesses of BCA as a normative science. Yes, "normative science"
      is an oxymoron, and the incongruity it speaks to is a source of much of the
      controversy; BCA is an imperfect answer, but often the best available answer, to
      the question of how a society should go about making collective but not unanimous
      choices. I also want to take a hard look at the question of what we are
      evaluating. BCA is designed to weigh government actions, to see whether they are
      in the public interest; it is not designed to evaluate private actions. But if
      the government action is to approve a private action that otherwise would be
      prohibited, then the BCA inevitably must evaluate the latter. From the
      perspective of a government regulator, it is very tempting to shift the burden of
      proof onto private innovators-to obligate them to seek permission to proceed, and
      to demonstrate that their proposed actions have acceptable risks and will produce
      a net social benefit. But such burden-shifting is not merely an administrative
      convenience; it has serious economic consequences that need to be examined.

PMID- 29453838
TI  - From CBA to Precautionary Appraisal: Practical Responses to Intractable Problems.
AB  - The purpose of this essay is to critically review the design of methods for
      ethically robust forms of technology appraisal in the regulation of research and
      innovation in synthetic biology. It will focus, in particular, on the extent to
      which cost-benefit analysis offers a basis for informing decisions about which
      technological pathways to pursue and which to discourage. A further goal is to
      consider what (if anything) the precautionary principle might offer in enabling
      better decisions. And this, in turn, raises questions about why mention of
      precaution can excite accusations of unscientific bias or irrational, "anti
      innovation" extremism. What does the polarized debate tell us about the politics
      around synthetic biology? In seeking more rigorous, timely, and practical ways to
      govern these remarkable new technologies, what might we be missing? The
      sophistication, diversity, and scope of synthetic biology may seem to make it a
      rather idiosyncratic area for exploring these general issues. It may seem to be a
      special case, with the bewildering pace of change amplifying the difficulties.
      But at root, some of the trickiest issues are just specific instances of familiar
      and long-standing conundrums in the governance of science and technology. The
      basic challenge is how to weigh up, for a wide range of potential options, the
      various pros and cons, as viewed from divergent perspectives, and find a way to
      justify the best course of action on behalf of society as a whole. This is the
      central problem addressed by a number of techniques in CBA. On the face of it,
      synthetic biology seems to present just one more application of these well
      established and self-confident prescriptive methods. But there do emerge several
      obstinate, even prohibitive, difficulties for CBA. Although they are well
      acknowledged by the scholarly literature on and around this topic, they are often
      sidelined in practice. Yet all are central to the case for applying the concept
      of precaution to a field like synthetic biology. This essay will briefly explore
      multicriteria mapping, an appraisal method for exploring contrasting perspectives
      on emerging technologies, as one practical way to address them. The essay focuses
      on MCM, not because it presents any sort of panacea for appraisal, but because it
      is illustrative of the concrete implications of precaution. Setting out even just
      one among potentially many practical alternative methods at least refutes the
      last-ditch argument that CBA is the only operational choice.

PMID- 29453839
TI  - Making Policies about Emerging Technologies.
AB  - Can we make wise policy decisions about still-emerging technologies-decisions
      that are grounded in facts yet anticipate unknowns and promote the public's
      preferences and values? There is a widespread feeling that we should try. There
      also seems to be widespread agreement that the central element in wise decisions
      is the assessment of benefits and costs, understood as a process that consists,
      at least in part, in measuring, tallying, and comparing how different outcomes
      would affect the public interest. But how benefits and costs are best weighed
      when making decisions about whether to move forward with an emerging technology
      is not clear. Many commentators feel that the weighing is often inadequate or
      inappropriate. Those who argue for a "precautionary" approach to the weighing do
      so precisely because they feel the need for a restraint on the dominant decision
      making tools and processes for assessing outcomes. This Hastings Center special
      report examines those tools and processes, taking the method known as cost
      benefit analysis as a starting point. In U.S. governance, CBA, sometimes informed
      by risk assessment, is the most widely used and extensively studied method, and
      authoritative reports on genetic and reproductive technologies often use language
      suggestive of cost-benefit analysis. There is also a long-running debate about
      the role of values in CBA and other formal impact assessment mechanisms-and about
      how those mechanisms compare to the precautionary principle. The guiding idea in
      the report is to engage in a close examination of the strengths and limits of CBA
      for ensuring that emerging technologies are used in ways that square with the
      public's values, drawing on applications of synthetic biology to illustrate and
      sharpen the analysis and then considering corrections to CBA and some alternative
      methodologies that handle values differently.

PMID- 29453840
TI  - About the Special Report.

PMID- 29453841
TI  - Beyond Cost-Benefit Analysis in the Governance of Synthetic Biology.
AB  - For many innovations, oversight fits nicely within existing governance
      mechanisms; nevertheless, others pose unique public health, environmental, and
      ethical challenges. Synthetic artemisinin, for example, has many precursors in
      laboratory-developed drugs that emulate natural forms of the same drug. The
      policy challenges posed by synthetic artemisinin do not differ significantly in
      kind from other laboratory-formulated drugs. Synthetic biofuels and gene drives,
      however, fit less clearly into existing governance structures. How many of the
      new categories of products require new forms of regulatory oversight, or at least
      extensive forms of testing, remains unclear. Any effort to improve the governance
      of synthetic biology should start with a rich understanding of the different
      possible science-policy interfaces that could help to inform governance. CBA
      falls into a subset of the overall range of possibilities, and which interface is
      appropriate may turn out to depend on context, on the demands of the decision at
      hand. In what follows, we lay out a typology of interfaces. After that, we turn
      to the question of how to draw upon the range of possible interfaces and
      effectively address the factual and moral complexities of emerging technologies.
      We propose a governance model built around structures that we call "governance
      coordinating committees." GCCs are intended to be mechanisms for accommodating
      the complexities of innovations that have far-ranging societal impacts. The
      production of biofuels, for example, could contaminate water supplies and have a
      destructive environmental impact if not managed correctly. The introduction of a
      gene drive could have economic and environmental impacts that are not restricted
      to one nation. Forging appropriate means for determining and evaluating those
      societal impacts, to the best of a corporation's, industry's, or government's
      ability, is central to responsible research and innovation. Public policy must be
      shaped in a manner that accommodates as many concerns as possible and minimizes
      risks.

PMID- 29453842
TI  - About The Hastings Center.

PMID- 29453843
TI  - Behavioral Economics and the Public Acceptance of Synthetic Biology.
AB  - Different applications of synthetic biology are alike in that their possible
      negative consequences are highly uncertain, potentially catastrophic, and perhaps
      irreversible; therefore, they are also alike in that public attitudes about them
      are fertile ground for behavioral economic phenomena. Findings from behavioral
      economics suggest that people may not respond to such applications according to
      the normal rules of economic evaluation, by which the value of an outcome is
      multiplied by the mathematical probability that the outcome will occur. Possibly,
      then, synthetic biology applications challenge the normative postulates of the
      standard approach, too. I want to first consider how some of the phenomena
      described by behavioral economists-and behavioral scientists more broadly-might
      affect people's perceptions of the uncertainties associated with synthetic
      biology. My analysis will be far from complete, however, because behavioral
      economics is essentially the study of human behavior, and thus its reach is
      potentially vast and its development longstanding and ongoing. Nonetheless, I
      hope to give an indicative perspective on how some aspects of behavioral
      economics might affect the assessment and perceived acceptability of synthetic
      biology. I will then consider the issue of agency. Should policy-makers respect
      people's reactions to synthetic biology when those reactions are known to be
      driven by behavioral economic phenomena rather than following the normative
      postulates of rational choice theory? Or should policy-makers dismiss these
      reactions as inherently biased? I will argue that the normative force of these
      human reactions (probably) depends on phenomenon and context.

PMID- 29453844
TI  - Integrating Scenario Planning and Cost-Benefit Methods.
AB  - By their nature, the most vexing social problems reflect collisions between
      social and economic interests of parties with highly divergent views and
      perspectives on the cause and character of what is at issue and the consequences
      that flow from it. Conflicts around biotechnology applications are good examples
      of these problems. When considering the potential consequences of proposed
      biotechnology applications, an enormous range of perspectives arise reflecting
      the breadth of different and often competing interests with a stake in life's
      future. This essay starts from an assumption that the traditional tool of cost
      benefit analysis is not adequate for adjudicating competing claims around the
      introduction of new biotechnology applications. It tends to require implicit
      simplifying assumptions that reduce or mask true underlying levels of complexity
      and uncertainty, and the results it produces deliver a definitive and singular
      answer, as opposed to a multiplicity of outcomes. In this essay, I describe some
      of the key elements of formal scenario planning to show how CBA could be
      redeployed as a supporting tool within the broader decision support methodology
      of formal scenario planning.

PMID- 29453846
TI  - Fabrication of miniature elastomer lenses with programmable liquid mold for
      smartphone microscopy: curing polydimethylsiloxane with in situ curvature
      control.
AB  - Miniature lenses can transform commercial imaging systems, e.g., smartphones and
      webcams, into powerful, low-cost, handheld microscopes. To date, the reproducible
      fabrication of polymer lenses is still a challenge as they require controlled
      dispensing of viscous liquid. This paper reports a reproducible lens fabrication
      technique using liquid mold with programmable curvature and off-the-shelf
      materials. The lens curvature is controlled during fabrication by tuning the
      curvature of an interface of two immiscible liquids [polydimethylsiloxane (PDMS)
      and glycerol]. The curvature control is implemented using a visual feedback
      system, which includes a software-based guiding system to produce lenses of
      desired curvature. The technique allows PDMS lens fabrication of a wide range of
      sizes and focal lengths, within 20 min. The fabrication of two lens diameters: 1
      and 5 mm with focal lengths ranging between 1.2 and 11 mm are demonstrated. The
      lens surface and bulk quality check performed using X-ray microtomography and
      atomic force microscopy reveal that the lenses are suitable for optical imaging.
      Furthermore, a smartphone microscope with ~1.4-MUm resolution is developed using
      a self-assembly of a single high power fabricated lens and microaperture. The
      lenses have various potential applications, e.g., optofluidics, diagnostics,
      forensics, and surveillance.

PMID- 29453847
TI  - Fiber bundle endomicroscopy with multi-illumination for three-dimensional
      reflectance image reconstruction.
AB  - Bundled fiber optics allow in vivo imaging at deep sites in a body. The intrinsic
      optical contrast detects detailed structures in blood vessels and organs. We
      developed a bundled-fiber-coupled endomicroscope, enabling stereoscopic three
      dimensional (3-D) reflectance imaging with a multipositional illumination scheme.
      Two illumination sites were attached to obtain reflectance images with left and
      right illumination. Depth was estimated by the horizontal disparity between the
      two images under alternative illuminations and was calibrated by the targets with
      known depths. This depth reconstruction was applied to an animal model to obtain
      the 3-D structure of blood vessels of the cerebral cortex (Cereb cortex) and
      preputial gland (Pre gla). The 3-D endomicroscope could be instrumental to
      microlevel reflectance imaging, improving the precision in subjective depth
      perception, spatial orientation, and identification of anatomical structures.

PMID- 29453848
TI  - Postoperative Recurrence of Crohn's Disease: Pathophysiology, Diagnosis and
      Treatment.
AB  - BACKGROUND: Abstract: Up to 80% of Crohn's disease (CD) patients require at least
      one surgical intervention in their lifetime and up to 70% of these patients
      develop postoperative endoscopic recurrence within 1 year. METHODS: The most
      important predictors of early postoperative recurrence are represented by
      smoking, prior intestinal surgery, penetrating disease and perianal location.
      Genetic factors, gut microbiota structure and immunological alterations may be
      involved in the pathogenesis of postoperative recurrence of CD, although their
      specific roles have to be determined yet. RESULTS: Different drugs, such as
      metronidazole, thiopurines and anti-tumor necrosis factor alpha (anti- TNFalpha)
      have been shown to reduce the risk of recurrence in many clinical trials,
      although the choice of the drug should take into consideration the benefits, the
      potential side effects and also the costs. Patients who are at high risk for
      postoperative recurrence should be considered for early medical prophylaxis with
      thiopurines or anti-TNFalpha drugs; on the contrary, patients who do not have
      risk factors may receive no treatment or receive a course of antibiotic or
      mesalazine followed by tailored therapy based on endoscopy at 6 months.
      CONCLUSION: Therefore, stratifying patients according to their risk of recurrence
      and tailoring therapy are at present the ideal and most cost-effective ways to
      treat operated CD patients, although many aspects require further evaluation.

PMID- 29453849
TI  - Methionine is required for cAMP-PKA-mediated morphogenesis and virulence of
      Candida albicans.
AB  - Candida albicans is a major human fungal pathogen, causing superficial, as well
      as life-threatening invasive infections. Therefore, it has to adequately sense
      and respond to the host defense by expressing appropriate virulence attributes.
      The most important virulence factor of C. albicans is the yeast-to-hyphae
      morphogenetic switch, which can be induced by numerous environmental cues,
      including the amino acid methionine. Here, we show an essential role for
      methionine permease Mup1 in methionine-induced morphogenesis, biofilm formation,
      survival inside macrophages and virulence. Furthermore, we demonstrate that this
      process requires conversion of methionine into S-adenosyl methionine (SAM) and
      its decarboxylation by Spe2. The resulting amino-propyl group is then used for
      biosynthesis of polyamines, which have been shown to activate adenylate cyclase.
      Inhibition of the SPE2 SAM decarboxylase gene strongly impairs methionine-induced
      morphogenesis on specific media and significantly delays virulence in the mouse
      systemic infection model system. Further proof of the connection between
      methionine uptake and initial metabolism and the cAMP-PKA pathway was obtained by
      showing that both Mup1 and Spe2 are required for cAMP production in response to
      methionine. Our results suggest that amino acid transport and further metabolism
      are interesting therapeutic targets as inhibitors of this may prevent the
      morphogenetic switch, thereby preventing virulence.

PMID- 29453850
TI  - The role of the immune system in kidney disease.
AB  - The immune system and the kidneys are closely linked. In health the kidneys
      contribute to immune homeostasis, while components of the immune system mediate
      many acute forms of renal disease and play a central role in progression of
      chronic kidney disease. A dysregulated immune system can have either direct or
      indirect renal effects. Direct immune-mediated kidney diseases are usually a
      consequence of autoantibodies directed against a constituent renal antigen, such
      as collagen IV in anti-glomerular basement membrane disease. Indirect immune
      mediated renal disease often follows systemic autoimmunity with immune complex
      formation, but can also be due to uncontrolled activation of the complement
      pathways. Although the range of mechanisms of immune dysregulation leading to
      renal disease is broad, the pathways leading to injury are similar. Loss of
      immune homeostasis in renal disease results in perpetual immune cell recruitment
      and worsening damage to the kidney. Uncoordinated attempts at tissue repair,
      after immune-mediated disease or non-immune mediated injury, result in fibrosis
      of structures important for renal function, leading eventually to kidney failure.
      As renal disease often manifests clinically only when substantial damage has
      already occurred, new diagnostic methods and indeed treatments must be identified
      to inhibit further progression and promote appropriate tissue repair. Studying
      cases in which immune homeostasis is re-established may reveal new treatment
      possibilities.

PMID- 29453851
TI  - Dicer inactivation stimulates limb regeneration ability in Xenopus laevis.
AB  - The ontogenetic decline of regeneration capacity in the anuran amphibian Xenopus
      makes it an excellent model for regeneration studies. However, the cause of the
      regeneration ability decline is not fully understood. MicroRNAs regulate animal
      development and have been indicated in various regeneration situations. However,
      little is known about the role of microRNAs during limb regeneration in Xenopus.
      This study investigates the effect of Dicer, an enzyme responsible for microRNA
      maturation, on limb development and regeneration in Xenopus. Dicer is expressed
      in the developing Xenopus limbs and is up-regulated after limb amputation during
      both regeneration-competent and regeneration-deficient stages of tadpole
      development. Inactivation of Dicer in early (NF stage 53) tadpole limb buds leads
      to shorter tibulare/fibulare formation but does not affect limb regeneration.
      However, in late-stage, regeneration-deficient tadpole limbs (NF stage 57), Dicer
      inactivation restores the regeneration blastema and stimulates limb regeneration.
      Thus, our results demonstrated that Xenopus limb regeneration can be stimulated
      by the inactivation of Dicer in nonregenerating tadpoles, indicating that
      microRNAs present in late-stage tadpole limbs may be involved in the ontogenetic
      decline of limb regeneration in Xenopus.

PMID- 29453852
TI  - A Sulfonozanamivir Analogue Has Potent Anti-influenza Virus Activity.
AB  - Influenza virus infection continues to cause significant, often severe,
      respiratory illness worldwide. A validated target for the development of anti
      influenza agents is the virus surface protein sialidase. In the current study, we
      have discovered a highly potent inhibitor of influenza virus sialidase, based on
      a novel sialosyl sulfonate template. The synthesised 3-guanidino sialosyl alpha
      sulfonate, a sulfonozanamivir analogue, inhibits viral replication in vitro at
      the nanomolar level, comparable to that of the anti-influenza drug zanamivir.
      Using protein X-ray crystallography we show that the sialosyl alpha-sulfonate
      template binds within the sialidase active site in a 1 C4 chair conformation. The
      C1-sulfonate moiety forms crucial and strong-binding interactions with the active
      site's triarginyl cluster, while the 3-guanidino moiety interacts significantly
      with conserved active site residues. This sulfonozanamivir analogue provides a
      new direction in anti-influenza virus drug development.

PMID- 29453854
TI  - Cost-effective innovations in low-resource settings.

PMID- 29453853
TI  - Role of bi-weekly serum galactomannan screening for the diagnosis of invasive
      aspergillosis in haematological cancer patients.
AB  - Invasive aspergillosis (IA) is a life-threatening infection affecting
      haematological cancer patients with chemotherapy-induced neutropenia. The
      diagnosis of IA often relies on the detection of galactomannan (GM) in serum or
      bronchoalveolar lavage fluid (BAL). Bi-weekly serum GM screening has been
      proposed for a pre-emptive therapeutic approach of IA in patients not receiving
      mold-active prophylaxis. We have analysed all IA cases among patients with
      haematological malignancies and prolonged chemotherapy-induced neutropenia (>14
      days) in our institution over a 10-year period (2007-2017). Serum GM was measured
      twice weekly and mold-active prophylaxis was not routinely administered. Thirty
      IA cases were observed and a positive serum GM was the first indicator of IA in
      10 (33%) of them, which represents a need of approximately 500 GM tests for the
      detection of a single IA case. In the other 20 (67%) cases, suggestive chest CT
      lesion was the first sign of IA and bronchoscopy was required in 15 (50%) cases
      with negative serum GM for establishing the diagnosis of probable/proven IA. A
      positive serum GM was associated with a worse prognosis (57% 12-week survival vs
      100% among serum GM-negative patients, P = .006), irrespective of the timing of
      GM positivity compared to CT. We concluded that bi-weekly serum GM screening
      demonstrated limited benefit in this population.

PMID- 29453855
TI  - Nerve reinnervation and itch behavior in a rat burn wound model.
AB  - In this study, we investigated whether postburn itch in rats, after a full
      thickness burn, is correlated to the nervous reinnervation of the burn wound
      area. For this purpose, we determined scratching duration (expressed as
      second/hour) at 24 hours, 2, 4, 8, and 12 weeks postburn and combined this with
      immunohistochemistry for protein gene product 9.5 (PGP9.5) to identify all nerve
      fibers, calcitonin gene related peptide (CGRP) to identify peptidergic fibers,
      tyrosine hydroxylase (TH) for sympathetic fibers, and growth-associated protein
      43 (GAP-43) for regrowing fibers. We found a modest, but highly significant,
      increase in scratching duration of all burn wound rats from 3 to 12 weeks
      postburn (maximally 63 +/- 9.5 second/hour compared to sham 3.1 +/- 1.4
      second/hour at 9 weeks). At 24 hours postburn, all nerve fibers had disappeared
      from the burn area. Around 4 weeks postburn PGP 9.5- and CGRP-immunoreactive
      nerve fibers returned to control levels. TH- and GAP-43-IR nerve fibers, which we
      found to be almost completely colocalized, did not regrow. No correlation was
      found between scratching duration and nervous reinnervation of the skin. The
      present results suggest that in rat, like in human, burn wound healing will
      induce increased scratching, which is not correlated to the appearance of nervous
      reinnervation.

PMID- 29453856
TI  - Defective RNA sensing by RIG-I in severe influenza virus infection.
AB  - Influenza virus infection causes worldwide seasonal epidemics. Although influenza
      is usually a mild disease, a minority of patients experience very severe
      fulminating disease courses. Previous studies have demonstrated a role for type I
      interferon (IFN) in anti-viral responses during influenza. So far, however, IFN
      regulatory factor (IRF)7 deficiency is the only genetic cause of severe influenza
      described in humans. In this study we present a patient with severe influenza A
      virus (IAV) H1N1 infection during the 2009 swine flu pandemic. By whole exome
      sequencing we identified two variants, p.R71H and p.P885S, located in the caspase
      activation and recruitment domain (CARD) and RNA binding domains, respectively,
      of DExD/H-box helicase 58 (DDX58) encoding the RNA sensor retinoic acid inducible
      gene 1 (RIG-I). These variants significantly impair the signalling activity of
      RIG-I. Similarly, patient cells demonstrate decreased antiviral responses to RIG
      I ligands as well as increased proinflammatory responses to IAV, suggesting
      dysregulation of the innate immune response with increased immunopathology. We
      suggest that these RIG-I variants may have contributed to severe influenza in
      this patient and advocate that RIG-I variants should be sought in future studies
      of genetic factors influencing single-stranded RNA virus infections.

PMID- 29453857
TI  - Psychosocial student functioning in comprehensive dental clinic education: A
      qualitative study.
AB  - INTRODUCTION: The aims were to describe first-year clinical dental students'
      psychosocial experiences in a known well-functioning comprehensive clinic
      teaching group (F+Grp) and a known dysfunctional group (Dys-Grp) and, thus,
      discover and describe phenomena related to psychosocial functioning of students.
      These groups were compared and contrasted regarding negative stress symptoms,
      perfectionism and coping with stress. METHODS: Eight female dental students (mean
      26 years old), four in each group, were interviewed after the first clinical year
      about learning and emotional experiences. The students also rated their perceived
      stress using a 0-10 scale, where 0 is no stress, and 10 is highest stress.
      Qualitative analyses involved searching for recurring themes and discovery of
      categories of clinical and social functioning. All 8 students were revisited as
      dentists after 8 years and filled out a 15-item survey as longitudinal validation
      of their first-year clinical experiences and to estimate group consensus and
      informant accuracy. RESULTS: Both groups suffered from negative stress symptoms
      attributed to lack of time for clinical tasks, worries about work quality with
      confusion about their own expectations and worries about how others perceived
      them. Dys-Grp experienced higher negative stress and maladaptive perfectionism
      and described crying behaviours, withdrawal and unwillingness to cooperate with
      others. In contrast, students in F+Grp provided rich content about mutual
      cooperation related to social networking and positive support. The 8 subjects
      exhibited high internal consistency (alpha  =  .98) in their responses to the
      follow-up survey about their first year of clinic. CONCLUSIONS: The comprehensive
      care teaching clinic environment with students working in groups appeared to
      provide a possibility for students to support each other for improved stress
      coping. Unfortunately, the opposite also occurred. Positive, supportive teacher
      supervision of student challenges related to perfectionism and stress is crucial
      and requires specific attention.

PMID- 29453858
TI  - Comorbidities of pyoderma gangrenosum: a retrospective multicentric analysis of
      126 patients.

PMID- 29453859
TI  - Diminished CXCR5 expression in peripheral blood of patients with Sjogren's
      syndrome may relate to both genotype and salivary gland homing.
AB  - Genetic investigations of Sjogren's syndrome (SS) have identified a
      susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. C
      X-C motif chemokine receptor 5 (CXCR5) is a chemokine receptor expressed on B and
      T cell subsets, and binds the chemotactic ligand C-X-C motif chemokine ligand 13
      (CXCL13). In this study we aimed to link the genetic association with functional
      effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait
      loci analysis of the 11q23.3 locus was performed using B cell mRNA expression
      data from genotyped individuals. Lymphocyte surface markers were assessed by flow
      cytometry, and CXCL13 levels by a proximity extension assay. CXCR5+ and CXCL13+
      cells in minor salivary glands were detected using immunohistochemistry. Our
      results demonstrated that SS-associated genetic polymorphisms affected the
      expression of CXCR5 (P < 0.01). Notably, a decreased percentage of CXCR5+ cells,
      with lower CXCR5 expression, was observed for most circulating B and T cell
      subsets in SS patients, reaching statistical significance in CD19+ CD27+
      immunoglobulin (Ig)D+ marginal zone (P < 0.001), CD19+ CD27+ IgD- memory (P <
      0.05) and CD27-IgD double-negative (P < 0.01) B cells and CD4+ CXCR3- CCR6+ Th17
      cells (P < 0.05). CXCL13 levels were increased in patient plasma (P < 0.001), and
      immunohistochemical staining revealed expression of CXCL13 and higher numbers of
      CXCR5+ cells (P < 0.0001) within focal infiltrates and interstitially in salivary
      glands of SS patients. In conclusion, we link a genetic susceptibility allele for
      SS to a functional phenotype in terms of decreased CXCR5 expression. The decrease
      of CXCR5+ cells in circulation was also related to homing of B and T cells to the
      autoimmune target organ. Therapeutic drugs targeting the CXCR5/CXCL13 axis may be
      useful in SS.

PMID- 29453861
TI  - Virus-Like Particle Engineering: From Rational Design to Versatile Applications.
AB  - As mimicking natural virus structures, virus-like particles (VLPs) have evolved
      to become a widely accepted technology used for humans which are safe, highly
      efficacious, and profitable. Several remarkable advantages have been achieved to
      revolutionize the molecule delivery for diverse applications in nanotechnology,
      biotechnology, and medicine. Here, the rational structure design, manufacturing
      process, functionalization strategy, and emerging applications of VLPs is
      reviewed. The situation and challenges in the VLP engineering, the key
      development orientation, and future applications have been discussed. To develop
      a good VLP design concept, the virus/VLP-host interactions need to be examined
      and the screening methods of the VLP stabilization factors need to be
      established. The functionalization toolbox can be expanded to fabricate smart,
      robust, and multifunctional VLPs. Novel robust VLP manufacturing platforms are
      required to deliver vaccines in resource-poor regions with a significant
      reduction in the production time and cost. The future applications of VLPs are
      always driven by the development of emerging technologies and new requirements of
      modern life.

PMID- 29453860
TI  - Fungal infections in patients with inflammatory bowel disease: A systematic
      review.
AB  - BACKGROUND: Despite reports of fungal infections in patients with inflammatory
      bowel disease (IBD), their clinical and microbiological characteristics remain
      unknown. OBJECTIVES: The aim of this systematic review was to examine all
      available evidence regarding fungal infections in patients with IBD. METHODS:
      Systematic search of PubMed (through 27 May 2017) for studies providing data on
      clinical, microbiological, treatment and outcome data of fungal infections in
      patients with IBD. The primary study outcome was to record the most common fungal
      species in patients with IBD. Secondary outcomes were classified into 3
      categories: (i) characteristics of fungal infections; (ii) data on IBD and (iii)
      treatment and outcomes of fungal infections in patients with IBD. RESULTS:
      Fourteen studies with data on 1524 patients were included in final analysis. The
      most common fungal infections in patients with IBD were caused by Candida species
      (903 infections); the most commonly reported site of Candida infection was the
      gastrointestinal tract. Available evidence shows that most fungal infections
      occur within 12 months of IBD treatment and within 6 months when anti-TNFa agents
      are used. CONCLUSIONS: This systematic review thoroughly describes fungal
      infections in patients with IBD and provides important information for the early
      detection and management of these infections.

PMID- 29453862
TI  - Insights into transcriptional silencing and anti-silencing in Shigella flexneri:
      a detailed molecular analysis of the icsP virulence locus.
AB  - Transcriptional silencing and anti-silencing mechanisms modulate bacterial
      physiology and virulence in many human pathogens. In Shigella species, many
      virulence plasmid genes are silenced by the histone-like nucleoid structuring
      protein H-NS and anti-silenced by the virulence gene regulator VirB. Despite the
      key role that these regulatory proteins play in Shigella virulence, their
      mechanisms of transcriptional control remain poorly understood. Here, we
      characterize the regulatory elements and their relative spacing requirements
      needed for the transcriptional silencing and anti-silencing of icsP, a locus that
      requires remotely located regulatory elements for both types of transcriptional
      control. Our findings highlight the flexibility of the regulatory elements'
      positions with respect to each other, and yet, a molecular roadblock docked
      between the VirB binding site and the upstream H-NS binding region abolishes
      transcriptional anti-silencing by VirB, providing insight into transcriptional
      anti-silencing. Our study also raises the need to re-evaluate the currently
      proposed VirB binding site. Models of transcriptional silencing and anti
      silencing at this genetic locus are presented, and the implications for
      understanding these regulatory mechanisms in bacteria are discussed.

PMID- 29453863
TI  - Aeromonas hydrophila from marketed mullet (Mugil cephalus) in Egypt: PCR
      characterization of beta-lactam resistance and virulence genes.
AB  - AIMS: Aeromonas hydrophila has been isolated from various fish species in Egypt
      and is known to carry virulence and antimicrobial resistance genes, which pose a
      risk for public health. The aim of the present study is to report, for the first
      time, the infection of mullet (Mugil cephalus) with A. hydrophila and to clarify
      the potential association between antimicrobial resistance and virulence traits
      encoded in A. hydrophila. METHODS AND RESULTS: In this study, the occurrence of
      A. hydrophila in marketed mullet and the antimicrobial resistance phenotypes of
      these isolates were determined. Aeromonas hydrophila isolates were screened for
      the presence of virulence and beta-lactam resistance genes; the correlation
      between both gene groups was also investigated. The infection rate of examined
      mullet with A. hydrophila was 37% (50/135). The highest antimicrobial resistance
      was detected to cefoxitin (100%), followed by ampicillin (84%), ceftazidime (56%)
      and cefotaxime (40%). Only 4% of the isolates were resistant to erythromycin; 6%
      were resistant to both gentamicin and kanamycin with no resistance to
      ciprofloxacin. Variable frequencies of virulence and beta-lactam resistance genes
      were evident from PCR, where aerA and blaTEM predominated. The study also
      indicated a general weak positive correlation (R = 0.3) between both virulence
      and beta-lactam resistance genes. Some of the studied virulence genes (e.g.
      aerA:hlyA and hlyA:ast) were found to correlate positively. CONCLUSIONS: The
      presence of virulence and resistance genes in A. hydrophila from food sources
      poses a serious threat to public health. To our knowledge, this is the first
      report describing the occurrence of A. hydrophila in mullet and highlighting the
      coexistence of virulence and beta-lactam resistance genes encoded by these
      bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: These data provide insights into
      the potential association of antimicrobial resistance and virulence genes in A.
      hydrophila from marketed mullet in Egypt, which could pose threats to humans even
      if a weak positive correlation exists between both genes.

PMID- 29453865
TI  - Ulcerated Nodule of the Fingernail.

PMID- 29453866
TI  - Comorbidities in Autoimmune Skin Diseases.

PMID- 29453864
TI  - LPCAT1 controls phosphate homeostasis in a zinc-dependent manner.
AB  - All living organisms require a variety of essential elements for their basic
      biological functions. While the homeostasis of nutrients is highly intertwined,
      the molecular and genetic mechanisms of these dependencies remain poorly
      understood. Here, we report a discovery of a molecular pathway that controls
      phosphate (Pi) accumulation in plants under Zn deficiency. Using genome-wide
      association studies, we first identified allelic variation of the Lyso
      PhosphatidylCholine (PC) AcylTransferase 1 (LPCAT1) gene as the key determinant
      of shoot Pi accumulation under Zn deficiency. We then show that regulatory
      variation at the LPCAT1 locus contributes significantly to this natural variation
      and we further demonstrate that the regulation of LPCAT1 expression involves
      bZIP23 TF, for which we identified a new binding site sequence. Finally, we show
      that in Zn deficient conditions loss of function of LPCAT1 increases the
      phospholipid Lyso-PhosphatidylCholine/PhosphatidylCholine ratio, the expression
      of the Pi transporter PHT1;1, and that this leads to shoot Pi accumulation.

PMID- 29453867
TI  - Inpatient Dermatologists-Crucial for the Management of Skin Diseases in
      Hospitalized Patients.

PMID- 29453868
TI  - Coexistent Solid Malignancies in Pemphigus: A Population-Based Study.
AB  - Importance: The association of pemphigus vulgaris and pemphigus foliaceus with
      comorbid malignancies is yet to be firmly established. Objective: To estimate the
      association between pemphigus and a wide range of nonhematologic malignancies
      using one of the largest cohorts of patients with pemphigus to date. Design,
      Setting, and Participants: For this cross-sectional study, we used the
      computerized database of Clalit Health Services, the largest public health care
      provider organization in Israel insuring 4.4 million individuals in the settings
      of general community clinics, primary care and referral centers, and ambulatory
      and hospitalized health care. The study included 1985 patients with pemphigus and
      9874 control patients and was conducted from January 2004 to December 2014. Main
      Outcomes and Measures: The prevalence of 17 different solid malignancies was
      compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity
      matched control patients; chi2 and t tests were used for univariate analysis, and
      a logistic regression model was used for multivariate analysis. The association
      was examined following a sensitivity analysis that included only cases treated
      with long-term pemphigus-specific medications (corticosteroids,
      immunosuppressants, or rituximab), and following the adjustment for several
      confounding factors. Results: Overall, the total sample included 11 859 eligible
      patients, of whom 1985 were patients with pemphigus (mean [SD] age at
      presentation, 72.1 [18.5] years; 1188 women [59.8%]). In patients with pemphigus
      compared with control patients, there was a greater prevalence of esophageal
      cancers (0.4% vs 0.1%; odds ratio [OR], 2.9; 95% CI, 1.1-7.4) and laryngeal
      cancers (0.6% vs 0.3%; OR, 2.0; 95% CI, 1.0-4.1). No significant associations
      between pemphigus and other solid malignancies were observed. Estimates were not
      altered significantly after controlling for comorbidities, health care
      overutilization, immunosuppressive therapy, and other malignancy-specific risk
      factors (ie, smoking and alcohol abuse in laryngeal cancer, gastroesophageal
      reflux disease in esophageal cancer). Conclusions and Relevance: Significant
      associations were observed between pemphigus and solid malignancies of the larynx
      and the esophagus. Physicians treating patients with pemphigus should be aware of
      these findings. Further observational studies are warranted to establish this
      association in other cohorts.

PMID- 29453869
TI  - Erythema Nodosum-like Eruption in the Setting of Sorafenib Therapy.

PMID- 29453870
TI  - Comparison of Melanocyte Density Counts in Topical Imiquimod-Treated Skin
      Surrounding Lentigo Maligna vs Control Biopsy Specimens.

PMID- 29453871
TI  - Examining the Incidence and Presentation of Melanoma in the Cardiothoracic
      Transplant Population.
AB  - Importance: The immunosuppression vital to maintaining transplanted organs comes
      with an increased incidence of cutaneous neoplasms. Understanding the genesis of
      malignant melanoma (MM) in transplant subpopulations is necessary for adequate
      disease surveillance. Objective: To determine the incidence and timing of
      presentation of MM in the cardiothoracic (heart and/or lung) transplant (CTT)
      population. Design, Setting, and Participants: This was a retrospective cohort
      study of 1164 patients who underwent a CTT from 2001 through 2016 with a median
      follow-up time of 4.3 years. The study was performed at a single academic,
      tertiary referral center. The retrospective database was used to identify 1164
      patients who underwent a CTT at Duke University Hospital from 2001 to 2016. Ten
      patients were excluded from the study owing to a history of MM, resulting in 1154
      patients in the study. Five patients who developed MM after CTT were identified.
      Exposures: Exposures included tacrolimus, prednisone, and mycophenolate mofetil.
      Main Outcomes and Measures: The primary outcome measurement was the MM incidence.
      Secondary outcomes included time to diagnosis and survival. Results: Five of 1154
      patients who underwent a CTT (0.4%) developed biopsy-proven MM at a median follow
      up time of 4.3 years after transplantation at a median age of 64.5 years (range,
      31.0-74.0 years). Of the 1154 patients, 923 (80%) were men. Their mean (SD) age
      range was 63.8 years (27.2-68.2 years). Four patients (80%) presented with stage
      I disease while 1 (20%) presented with stage IV disease at a median time of 2.5
      years (range, 0.1-5.3 years) after transplant compared with a median time of 6.2
      years (range, 0.9-8.7 years) in Duke University's renal transplant population at
      a median follow-up time of 6.6 years. Two patients died after transplant, 1 owing
      to complications of the transplant and 1 owing to metastatic MM. Conclusions and
      Relevance: Representing one of the largest reported studies of patients with CTT
      developing MM, our findings suggest that the CTT population experiences an
      incidence of MM similar to that of other solid organ transplant recipients and
      with a median of 2.5 years from transplant to melanoma diagnosis. While the small
      scale of our study prevents far-reaching conclusions, further study is warranted
      to better understand the incidence, timing, and clinical ramifications of
      melanomagenesis in the CTT population.

PMID- 29453872
TI  - Effect of Dermatology Consultation on Outcomes for Patients With Presumed
      Cellulitis: A Randomized Clinical Trial.
AB  - Importance: Each year, cellulitis leads to 650 000 hospital admissions and is
      estimated to cost $3.7 billion in the United States. Previous literature has
      demonstrated a high misdiagnosis rate for cellulitis, which results in
      unnecessary antibiotic use and health care cost. Objective: To determine whether
      dermatologic consultation decreases duration of hospital stay or intravenous
      antibiotic treatment duration in patients with cellulitis. Design, Setting, and
      Participants: This randomized clinical trial was conducted in a large urban
      tertiary care hospital between October 2012 and January 2017, with 1-month follow
      up duration. Patients were randomized to the control group, which received the
      standard of care (ie, treatment by primary medicine team), or the intervention
      group, which received dermatology consultation. Medical chart review of
      demographic information and hospital courses was performed. Adult patients
      hospitalized with presumed diagnosis of cellulitis were eligible. A total of 1300
      patients were screened, 1125 were excluded, and 175 were included. Statistical
      analysis was employed to identify significant outcome differences between the 2
      groups. Interventions: Dermatology consultation within 24 hours of
      hospitalization. Main Outcomes and Measures: Length of hospital stay and duration
      of intravenous antibiotic treatment. Results: Of 175 participants, 70 (40%) were
      women and 105 (60%) were men. The mean age was 58.8 years. Length of hospital
      stay was not statistically different between the 2 groups. The duration of
      intravenous antibiotic treatment (<4 days: 86.4% vs 72.5%; absolute difference,
      13.9%; 95% CI, 1.9%-25.9%; P = .04) and duration of total antibiotic treatment
      was significantly lower in patients who had early dermatology consultation (<10
      days: 50.6% vs 32.5%; absolute difference, 18.1%; 95% CI, 3.7%-32.5%; P = .01).
      Clinical improvement at 2 weeks was significantly higher for those in the
      intervention group (79 [89.3%] vs 59 [68.3%]; absolute difference, 21.0%; 95% CI,
      9.3%-32.7%; P < .001). There was no significant difference in 1-month readmission
      rate between the groups (4 [4.5%] vs 6 [6.9%]; absolute difference, -2.4%; 95%
      CI, -9.3% to 4.5%; P = .54). In the intervention group, the rate of cellulitis
      misdiagnosis was 30.7% (27 of 88 participants). Among the entire cohort, 101
      (57.7%) patients were treated with courses of antibiotics longer than what is
      recommended by guidelines. Conclusions and Relevance: Early dermatologic
      consultation can improve outcomes in patients with suspected cellulitis by
      identifying alternate diagnoses, treating modifiable risk factors, and decreasing
      length of antibiotic treatment. Trial Registration: clinicaltrials.gov
      Identifier: NCT01706913.

PMID- 29453873
TI  - Association Between Pemphigus and Neurologic Diseases.
AB  - Importance: The association between pemphigus and neurologic diseases was not
      evaluated systematically in the past. In a recent uncontrolled cross-sectional
      study, Parkinson disease was found to be significantly associated with pemphigus;
      in the same study, epilepsy had a nonsignificant association with pemphigus.
      Several case reports have suggested that pemphigus coexists with multiple
      sclerosis and dementia. Objective: To estimate the association between pemphigus
      and 4 neurologic conditions (dementia, epilepsy, Parkinson disease, and multiple
      sclerosis), using one of the largest cohorts of patients with pemphigus. Design,
      Setting, and Participants: A retrospective population-based cross-sectional study
      was performed between January 1, 2004, and December 31, 2014, using the database
      of Clalit Health Services, the largest public health care organization in Israel,
      in the setting of general community clinics, primary care and referral centers,
      and ambulatory and hospitalized care. A total of 1985 patients with a new
      diagnosis of pemphigus and 9874 controls were included in the study. Main
      Outcomes and Measures: The proportion of dementia, epilepsy, Parkinson disease,
      and multiple sclerosis was compared between patients diagnosed with pemphigus and
      age-, sex-, and ethnicity-matched control participants. Logistic regression was
      used to calculate odds ratios (ORs) for dementia, epilepsy, Parkinson disease,
      and multiple sclerosis. The association was examined after a sensitivity analysis
      that included only patients treated with long-term, pemphigus-specific
      medications (corticosteroids, immunosuppressants, or rituximab) and after
      adjustment for several confounding factors. Results: When comparing the 1985
      cases (1188 women and 797 men; mean [SD] age, 72.1 [18.5] years) with the 9874
      controls (5912 women and 3962 men; mean [SD] age, 72.1 [18.5] years), dementia
      was seen in 622 cases (31.3%) vs 1856 controls (18.8%), with an OR of 1.97 (95%
      CI, 1.77-2.20). Epilepsy was present in 74 cases (3.7%) vs 210 controls (2.1%),
      with an OR of 1.78 (95% CI, 1.36-2.33). Parkinson disease was seen in 175 cases
      (8.8%) vs 437 controls (4.4%), with an OR of 2.09 (95% CI, 1.74-2.51). Multiple
      sclerosis was present in 2 cases (0.1%) vs 6 controls (0.01%), with an OR of 1.65
      (95% CI, 0.34-8.22). Study findings were robust to sensitivity analysis that
      included patients receiving pemphigus-specific treatments. Estimates were not
      altered significantly after controlling for comorbidities and overuse of health
      care. Conclusions and Relevance: An association was observed between pemphigus
      and specific neurologic diseases, including dementia, Parkinson disease, and
      epilepsy. Physicians treating patients with pemphigus should be aware of this
      possible association. Patients with pemphigus should be carefully assessed for
      comorbid neurologic disorders and receive appropriate treatment.

PMID- 29453875
TI  - Structural snapshots along the reaction mechanism of the atypical poplar
      thioredoxin-like2.1.
AB  - Plastidial thioredoxin (TRX)-like2.1 proteins are atypical thioredoxins
      possessing a WCRKC active site signature and using glutathione for recycling. To
      obtain structural information supporting the peculiar catalytic mechanisms and
      target proteins of these TRXs, we solved the crystal structures of poplar TRX
      like2.1 in oxidized and reduced states and of mutated variants. These structures
      share similar folding with TRXs exhibiting the canonical WCGPC signature.
      Moreover, the overall conformation is not altered by reduction of the catalytic
      disulfide bond or in a C45S/C67S variant that formed a disulfide-bridged dimer
      possibly mimicking reaction intermediates with target proteins. Modeling of the
      interaction of TRX-like2.1 with both NADPH- and ferredoxin-thioredoxin reductases
      (FTR) indicates that the presence of Arg43 and Lys44 residues likely precludes
      reduction by the plastidial FTR.

PMID- 29453874
TI  - Outcomes of Early Dermatology Consultation for Inpatients Diagnosed With
      Cellulitis.
AB  - Importance: Many inflammatory skin dermatoses mimic cellulitis (pseudocellulitis)
      and are treated with antibiotics and/or hospitalization, leading to unnecessary
      patient morbidity and substantial health care spending. Objective: To evaluate
      the impact of early dermatology consultation on clinical and economic outcomes
      associated with misdiagnosed cellulitis. Design, Setting, and Participants: This
      prospective cohort study enrolled patients with presumed diagnosis of cellulitis
      in the emergency department, in the emergency department observation unit, or
      within 24 hours of admission to an inpatient unit of a large urban teaching
      hospital between February and September 2017. Patients were provided with
      telephone and clinic follow-up during the 30-day postdischarge period. We
      screened 165 patients with the primary concern of cellulitis. Of these, we
      excluded 44 who required antibiotics for cutaneous, soft-tissue, and deeper
      tissue and/or bone infections irrespective of cellulitis status, and 5 who were
      scheduled to be discharged by the emergency department. Interventions: Early
      dermatology consultation for presumed cellulitis. Main Outcomes and Measures:
      Primary outcomes were patient disposition and rates of antibiotic use. Results:
      Of 116 patients (63 [54.3%] women; 91 [78.4%] non-Hispanic white; mean [SD] age,
      58.4 [19.1] years), 39 (33.6%) were diagnosed with pseudocellulitis by
      dermatologists. Of these, 34 (87.2%) had started using antibiotics for presumed
      cellulitis as prescribed by the primary team at the time of enrollment. The
      dermatology team recommended antibiotic discontinuation in 28 of 34 patients
      (82.4%), and antibiotics were stopped in 26 of 28 cases (92.9%). The
      dermatologists also recommended discharge from planned observation or inpatient
      admission in 20 of 39 patients with pseudocellulitis (51.3%), and the primary
      team acted on this recommendation in 17 of 20 cases (85.0%). No patients
      diagnosed with pseudocellulitis experienced worsening condition after discharge
      based on phone and clinic follow-up (30 of 39 [76.9%] follow-up rate).
      Extrapolating the impact of dermatology consultation for presumed cellulitis
      nationally, we estimate 97 000 to 256 000 avoided hospitalization days, 34 000 to
      91 000 patients avoiding unnecessary antibiotic exposure, and $80 million to $210
      million in net cost savings annually. Conclusions and Relevance: Early
      consultation by dermatologists for patients with presumed cellulitis represents a
      cost-effective intervention to improve health-related outcomes through the
      reduction of inappropriate antibiotic use and hospitalization.

PMID- 29453876
TI  - Prognostic importance of FGF2 and FGFR1 expression for patients affected by
      ameloblastoma.
AB  - BACKGROUND: Fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) have
      been investigated in different human neoplasms and were shown to play important
      roles in the pathogenesis of these diseases; however, very few are known
      regarding their prognostic importance in the context of ameloblastoma. Therefore,
      the aim of this study was to investigate whether the expression of FGF2 and FGFR1
      is associated with ameloblastoma clinical behavior. METHODS: Fifty-eight cases of
      ameloblastoma arranged in tissue microarray were submitted to
      immunohistochemistry against FGF2 and FGFR1. Clinicopathological parameters
      regarding sex, age, tumor size, duration and location, treatment, recurrences,
      radiographic features, cortical disruptions, and follow-up data were obtained
      from patients' medical records and correlated with the molecules expression.
      Univariate and multivariate Cox regression analyses were used to investigate the
      prognostic potential of the biomarkers. RESULTS: Forty-four cases (75.9%)
      exhibited cytoplasmic positivity for FGF2 in central and peripheral epithelial
      cells, 46 of 58 (79.3%) showed FGFR1 cytoplasmic positivity predominantly in the
      columnar peripheral cells, and 43 cases (74.1%) were positive for both.
      Expression of FGF2 and FGF2 + FGFR1 was associated with tumor recurrences (P =
      .05). However, univariate and multivariate analyses did not demonstrate a
      significant influence of FGF2, FGFR1, or FGF2 + FGFR1 in the 5-year disease-free
      survival (DFS) rate (P = .27, P = .33, and P = .25, respectively). CONCLUSION:
      Cytoplasmic expression of FGF2 and FGF2 + FGFR1 is associated with ameloblastoma
      recurrence, but FGF2 and FGFR1 are not determinants of a lower DFS.

PMID- 29453877
TI  - Significance of mitochondria on cardiometabolic syndromes.
AB  - Metabolic syndromes (MS) are a cluster of disorders such as obesity,
      hypertension, dyslipidemia, and diabetes. Cardiometabolic syndrome (CMS), a
      branch of MS, is a group of diseases affecting cardiovascular, renal, metabolic,
      prothrombotic, and inflammatory abnormalities due to defects in energy
      metabolism. Since the emergence of molecular biology and the discovery of
      pathogenic mitochondrial DNA defect in the 1980s, research advances have revealed
      a number of common human diseases involving mitochondrial dysfunction. One of the
      major defects in CMS and its associated diseases is excess cellular oxidative
      stress and oxidative damage to mitochondrial components. In this study, we
      overview specific aspects of mitochondrial biology that have contributed and
      likely will continue enhance the progress of development of therapeutics for CMS.
      During the last decade, however, increasing evidence has emerged supporting the
      role of mitochondrial functional parameters in the genesis of various metabolism
      related disorders. The biochemical pathways which modulate various mitochondrial
      functional indicators such as mitochondrial biogenesis, mitochondrial membrane
      potential, electron transport chain and ATP synthesis, intramitochondrial
      oxidative stress, and mitochondria-mediated cell death have been recognized in
      diagnosis and prognosis of various disorders associated with energy metabolism
      and heart function.

PMID- 29453878
TI  - Estimated glomerular filtration rate in stable older kidney transplant recipients
      are present algorithms valid? A national cross-sectional cohort study.
AB  - Several equations have been developed for estimated glomerular filtration rate
      (eGFR) in patients with chronic kidney disease (CKD), but none were developed
      based on data from elderly kidney transplant recipients (KTR). The primary aim of
      this study was to evaluate different creatinine-based equations in stable elderly
      KTR. A national cross-sectional study was performed using data from 263
      consecutive kidney transplant recipients 60 years or older who performed a
      routine GFR measurement one year after engraftment. GFR was measured by iohexol
      clearance calculation based on two samples. eGFR was calculated from a range of
      different creatinine-based equations using information obtained at the time of
      GFR measurement. Bias, precision, and accuracy were evaluated for each equation.
      All equations apart from Nankivell had accuracy (P30) > 80%. The BIS1, FAS, LMRCR
      , and Cockcroft & Gault equations in recipients older than 70 years and the FAS,
      LMRCR , and MDRD in recipients 60-69 years old had nonsignificant bias. The CKD
      EPI had significant bias in both groups. If one should choose a single equation
      for follow-up of individual CKD progression in all recipients >= 60 years, the
      FAS or LMRCR equations are probably the best alternatives.

PMID- 29453880
TI  - Information bias in epidemiological studies with a special focus on obstetrics
      and gynecology.
AB  - Information bias occurs when any information used in a study is either measured
      or recorded inaccurately. This paper describes some of the most common types of
      information bias, using examples from obstetrics and gynecology, and describes
      how information bias may affect results of observational studies. Non
      differential misclassification occurs when the degree of misclassification of
      exposure status among those with and those without the disease is the same; in
      cohort studies, this type of bias is most likely and will bias estimates toward
      no association when exposure is dichotomized. Non-differential underreporting of
      an exposure with more than two categories may mask a true threshold effect as a
      dose-response relation and, if a true threshold effect exists, the threshold will
      be set at too low a level, if the exposure is underreported. Differential
      misclassification may cause bias in either direction and is particularly likely,
      when exposure status is reported after the outcome occurred. Misclassification of
      confounders is an issue that needs special attention by researchers, as failure
      to measure accurately one or more (strong) confounders may seriously bias the
      observed results. Misclassification of disease status may also cause bias of
      estimates of association in either direction. Information bias is probably best
      prevented during planning of data collection, as there are few and insufficient
      methods available for correcting inaccurate information.

PMID- 29453879
TI  - Defining outcomes for beta-cell replacement therapy in the treatment of diabetes:
      a consensus report on the Igls criteria from the IPITA/EPITA opinion leaders
      workshop.
AB  - beta-cell replacement therapy, available currently as pancreas or islet
      transplantation, has developed without a clear definition of graft functional and
      clinical outcomes. The International Pancreas & Islet Transplant Association
      (IPITA) and European Pancreas & Islet Transplantation Association (EPITA) held a
      workshop to develop consensus for an IPITA/EPITA Statement on the definition of
      function and failure of current and future forms of beta-cell replacement
      therapy. There was consensus that beta-cell replacement therapy could be
      considered as a treatment for beta-cell failure, regardless of etiology and
      without requiring undetectable C-peptide, accompanied by glycemic instability
      with either problematic hypoglycemia or hyperglycemia. Glycemic control should be
      assessed at a minimum by glycated hemoglobin (HbA1c ) and the occurrence of
      severe hypoglycemia. Optimal beta-cell graft function is defined by near-normal
      glycemic control [HbA1c  <= 6.5% (48 mmol/mol)] without severe hypoglycemia or
      requirement for insulin or other antihyperglycemic therapy, and with an increase
      over pretransplant measurement of C-peptide. Good beta-cell graft function
      requires HbA1c  < 7.0% (53 mmol/mol) without severe hypoglycemia and with a
      significant (>50%) reduction in insulin requirements and restoration of
      clinically significant C-peptide production. Marginal beta-cell graft function is
      defined by failure to achieve HbA1c  < 7.0% (53 mmol/mol), the occurrence of any
      severe hypoglycemia, or less than 50% reduction in insulin requirements when
      there is restoration of clinically significant C-peptide production documented by
      improvement in hypoglycemia awareness/severity, or glycemic variability/lability.
      A failed beta-cell graft is defined by the absence of any evidence for clinically
      significant C-peptide production. Optimal and good functional outcomes are
      considered successful clinical outcomes.

PMID- 29453881
TI  - Identification of cancer-related potential biomarkers based on lncRNA-pseudogene
      mRNA competitive networks.
AB  - Accumulating evidence indicates that mRNAs and noncoding RNAs act as competitive
      endogenous RNAs (ceRNAs) and play a key role in tumorigenesis. However, the
      complex competitive relationship among genes remains unknown. In the present
      study, the long noncoding RNAs (lncRNAs), pseudogenes and mRNAs that compete with
      common microRNAs are defined as lncRNA-pseudogene-mRNA competitive triples. We
      find that some candidate ceRNAs, modules and triples are associated with cancers
      and can significantly divide patients into high-risk and low-risk groups; thus,
      they may serve as potential cancer biomarkers. In sum, the present study
      systematically analyzes the association between competitive triples and cancer,
      which provides a reference for a deeper understanding of cancer progression.

PMID- 29453882
TI  - Early kidney allograft loss-Is there scope for improvement?

PMID- 29453883
TI  - Entangled signal pathways can both control expression stability and induce
      stochastic focusing.
AB  - Gene transcription is often controlled by multiple interacting signal pathways,
      but how these pathways impact gene expression is not fully understood. Here, we
      refine a mechanic model based on experiments in murine embryonic stem cells and
      analyze the influence of pathway-pathway cross-talk strength (CTS) on mRNA
      expression stability. We find that the CTS can tune this stability, depending on
      the manner of regulation. Furthermore, there is an optimal CTS such that the
      expression pattern is most stable but free energy consumption is at its highest;
      the CTS can induce stochastic focusing of the mRNA level but this is at the cost
      of energy. In both cases, there is a cross-talk-mediated trade-off, implying that
      entangled signal pathways can control both expression stability and energy
      dissipation.

PMID- 29453884
TI  - Daratumumab resistance is frequent in advanced-stage multiple myeloma patients
      irrespective of CD38 expression and is related to dismal prognosis.
AB  - OBJECTIVE: Daratumumab is a promising new antimyeloma agent. We report a single
      center "real-world" series of multiple myeloma (MM) and amyloidosis (AL) patients
      treated with daratumumab. METHODS: Forty-one patients were included: 7 second
      line MM, 30 heavily pretreated (median number of therapies of 5) advanced MM, and
      4 with AL. RESULTS: Second-line patients and advanced AL showed high rate of
      durable overall responses. However, advanced MM patients had a dismal prognosis
      with an overall response rate (ORR) of 36%, and a short median progression-free
      and overall survival of 2.3 and 6.6 months, respectively. Responses were
      particularly poor in patients with extramedullary plasmacytomas. Neither the
      addition of another agent to daratumumab nor changing to the next line of therapy
      produced significant durable responses in this patient population. Flow cytometry
      analysis demonstrated that CD38 expression level was not predictive of response.
      We show that CD38 expression dynamics by a commercially available anti-CD38
      antibody after daratumumab administration was hindered by competitive binding of
      daratumumab. CONCLUSIONS: Responses to daratumumab and combinations in patients
      with advanced MM, particularly with extramedullary disease, are low and short
      lived, stressing the administration of this agent should be early in the course
      of the disease.

PMID- 29453885
TI  - Bacterial neuraminidase-mediated erythrocyte desialylation provokes cell surface
      aminophospholipid exposure.
AB  - BACKGROUND: Surface desialylation is associated with erythrocyte aging and
      mediates phagocytic recognition and clearance of senescent erythrocytes.
      Neuraminidases, a family of glycohydrolytic enzymes, cleave the glycosidic
      linkages between sialic acid and mucopolysaccharides and have previously been
      implicated in erythrocyte dysfunction associated with sepsis. Erythrocytes in
      septic patients further display a phenotype of accelerated eryptosis
      characterized by membrane phospholipid scrambling resulting in phosphatidylserine
      (PS) externalization. Herein, we examined the impact of artificial erythrocyte
      desialylation on eryptosis. METHODS: Using flow cytometry and/or fluorescence
      microscopy, we analyzed desialylation patterns and eryptotic alterations in
      erythrocytes exposed to Clostridium perfringens-derived neuraminidase. RESULTS:
      Exogenous bacterial neuraminidase significantly augmented membrane PS exposure
      and cytosolic Ca2+ levels in a dose- and time-dependent manner. Neuraminidase
      treatment significantly reduced fluorescence-tagged agglutinin binding, an effect
      temporally preceding the increase in PS externalization. Neuraminidase-induced PS
      exposure was significantly curtailed by pretreatment with the pan-sialidase
      inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid. Neuraminidase treatment
      further induced hemolysis but did not significantly impact erythrocyte volume,
      ceramide abundance, or the generation of reactive oxygen species. CONCLUSION:
      Collectively, our data reveal that alteration of erythrocyte sialylation status
      by bacterial neuraminidase favors eryptotic cell death, an effect potentially
      contributing to reduced erythrocyte lifespan and anemia in sepsis.

PMID- 29453886
TI  - Restructuring training in transplantation surgery ...and medicine: a necessity on
      both sides of the Atlantic.

PMID- 29453887
TI  - Coronary artery disease in heart transplantation: new concepts for an old
      disease.
AB  - Cardiac allograft vasculopathy (CAV) remains one of the main long-term
      complications after heart transplantation. We performed a systematic review
      focused on articles published in the previous 6 years to reappraise the novel
      evidences supporting risk factors, pathology, prevention, and treatment of CAV.
      We identified a search string for a literature search on PubMed. We excluded
      articles specifically focused on diagnosis/biomarkers/imaging only or
      complications of other diseases. We included 98 studies out of our search. Forty
      eight articles describe risk factors for CAV, 13 pathology, 24 prevention, and 13
      treatment for CAV. While confirming known concepts, we found supportive evidence
      that CAV pathophysiology may vary according to the time post-transplant and the
      prevalence of metabolic versus immune-mediated risk factors. Selective
      revascularization of focal lesions in patients with CAV may result in some
      clinical benefit, but CAV prevention, rather than treatment, by controlling risk
      factors and by using targeted immunosuppressive therapies is the most evidence
      based approach to reduce disease progression.

PMID- 29453888
TI  - Dual transcriptomics reveals co-evolutionary mechanisms of intestinal parasite
      infections in blue mussels Mytilus edulis.
AB  - On theoretical grounds, antagonistic co-evolution between hosts and their
      parasites should be a widespread phenomenon but only received little empirical
      support so far. Consequently, the underlying molecular mechanisms and
      evolutionary steps remain elusive, especially in nonmodel systems. Here, we
      utilized the natural history of invasive parasites to document the molecular
      underpinnings of co-evolutionary trajectories. We applied a dual-species
      transcriptomics approach to experimental cross-infections of blue mussel Mytilus
      edulis hosts and their invasive parasitic copepods Mytilicola intestinalis from
      two invasion fronts in the Wadden Sea. We identified differentially regulated
      genes from an experimental infection contrast for hosts (infected vs. control)
      and a sympatry contrast (sympatric vs. allopatric combinations) for both hosts
      and parasites. The damage incurred by Mytilicola infection and the following
      immune response of the host were mainly reflected in cell division processes,
      wound healing, apoptosis and the production of reactive oxygen species (ROS).
      Furthermore, the functional coupling of host and parasite sympatry contrasts
      revealed the concerted regulation of chitin digestion by a Chitotriosidase 1
      homolog in hosts with several cuticle proteins in the parasite. Together with the
      coupled regulation of ROS producers and antagonists, these genes represent
      candidates that mediate the different evolutionary trajectories within the
      parasite's invasion. The host-parasite combination-specific coupling of these
      effector mechanisms suggests that underlying recognition mechanisms create
      specificity and local adaptation. In this way, our study demonstrates the use of
      invasive species' natural history to elucidate molecular mechanisms of host
      parasite co-evolution in the wild.

PMID- 29453889
TI  - Mitochondrial dysfunction and axon degeneration in progressive multiple
      sclerosis.
AB  - The neuron is the target of inflammatory demyelinating processes in multiple
      sclerosis (MS). In progressive MS, however, there is a gathering body of evidence
      indicating that molecular changes converge on mitochondria within neuronal cell
      bodies. The most reproducible change relates to mitochondrial respiratory chain
      complex deficiency, which compromises the capacity of neurons to generate ATP.
      The resulting energy failure state is coupled with an increase in demand for
      energy by the demyelinated axon, being particularly relevant to the long tracts
      such as corticospinal tracts with long projection axons. Recent work in our
      laboratory and that of our collaborators indicates the limited reflection of the
      mitochondria changes within neurons in experimental disease models. The
      mitochondrial changes within neuronal compartments are likely to offer novel
      targets for the improvement in neuronal function in patients with progressive MS.

PMID- 29453890
TI  - The co-developmental dynamic of sport and school burnout among student-athletes:
      The role of achievement goals.
AB  - Student-athletes who strive for success in high-level sports while pursuing upper
      secondary education may be prone to sport and school burnout. This study examined
      the co-developmental dynamic of sport and school burnout in Finnish adolescent
      student-athletes (Ntime 1  = 391; Ntime 2  = 373) across the first year of upper
      secondary school using cross-lagged structural equation modeling (SEM).
      Furthermore, we used sport and school-related achievement goals as predictors of
      sport and school burnout, namely sport and school-related exhaustion, cynicism,
      and feelings of inadequacy. The results showed that burnout dimensions in a
      particular domain were substantially stable within the same domain during the
      first year of upper secondary school and that school-related exhaustion at the
      beginning of upper secondary school predicted sport-related exhaustion at the end
      of the school year. Mastery goals in sport and school were negatively associated
      with cynicism and feelings of inadequacy within the same domain. Furthermore,
      performance goals in school were positively associated with school-related
      cynicism. The results can be used by healthcare professionals for early
      prevention of student-athletes' burnout.

PMID- 29453891
TI  - An investigation of an open-access model for scaling up methadone maintenance
      treatment.
AB  - AIMS: To examine retrospectively patient and programmatic outcomes following the
      development and implementation of an 'open-access' model in which prospective
      patients were enrolled rapidly in methadone maintenance treatment, irrespective
      of ability to pay, and provided real-time access to multiple voluntary treatment
      options. DESIGN: Medical and administrative records were abstracted to compare
      data for 1 year before and 9 years after initiating the implementation of an open
      access treatment model in May 2007. SETTING: Methadone maintenance treatment
      center in Connecticut, USA. PARTICIPANTS: Individuals with opioid use disorder
      entering treatment between July 2006 and June 2015. In June 2015, 64% (n = 2594)
      of the sample were men and 80% (n = 3133) reported that they were white.
      INTERVENTION: The Network for the Improvement of Addiction Treatment-informed
      open-access treatment model uses process improvement strategies to improve
      treatment access and capacity. MEASUREMENTS: Census, waiting time, retention, non
      medical opioid use, patient mortality and financial sustainability (net income
      and state-block grants as proportions of revenue). FINDINGS: In the 9 years
      following the initial implementation of the open-access model, patient census
      increased by 183% from 1431 to 4051, and average waiting-time days decreased from
      21 to 0.3 (same day) without apparent deleterious effects on rates of retention,
      non-medical opioid use or mortality. Between fiscal years (FY) 06 and FY 15, net
      operating margin rose from 2 to 10%, while state-block grant revenues declined
      14% and the proportion of total revenue from state-block grant revenue decreased
      from 49 to 24%. CONCLUSIONS: An open-access model for rapid enrolment of people
      with opioid use disorder in methadone treatment appears to improve treatment
      access, capacity, and financial sustainability without evidence of deleterious
      effects on treatment outcomes.

PMID- 29453892
TI  - HIV-1 gp41 transmembrane oligomerization monitored by FRET and FCS.
AB  - The HIV-1 envelope gp120/gp41 trimer mediates viral membrane fusion. After
      cluster of differentiation-4 recognition, gp120 detaches from the virus, exposing
      gp41 which triggers fusion. During the fusion process, gp41 may not remain
      trimeric, which could have functional importance. Here, we probe the reversible
      association of full length gp41 (minus the cytoplasmic domain) in detergent
      micelles (with probes attached to transmembrane domain) by fluorescence resonance
      energy transfer (FRET) with a MUm dissociation constant. This is compared with
      other methods. A gp41-targeted fusion inhibitor must interfere with this
      transition, and monomeric, partially monomeric or trimeric states all present
      potential binding epitopes. The gp41 self-association is a valid drug target
      model and FRET, a potential high-throughput assay system, could be used to screen
      drug libraries.

PMID- 29453893
TI  - CBCT-guided evolutive library for cervical adaptive IMRT.
AB  - PURPOSE: In the context of adaptive radiation therapy (ART) for locally advanced
      cervical carcinoma (LACC), this study proposed an original cone-beam computed
      tomography (CBCT)-guided "Evolutive library" and evaluated it against four other
      known radiotherapy (RT) strategies. MATERIAL AND METHODS: For 20 patients who
      underwent intensity-modulated radiation therapy (IMRT) for LACC, three planning
      CTs [with empty (EB), intermediate (IB), and full (FB) bladder volumes], a CT
      scan at 20 Gy and bi-weekly CBCTs for 5 weeks were performed. Five RT strategies
      were simulated for each patient: "Standard RT" was based on one IB planning CT;
      "internal target volume (ITV)-based RT" was an ITV built from the three planning
      CTs; "RT with one mid-treatment replanning (MidTtReplan)" corresponded to the
      standard RT with a replanning at 20 Gy; "Pretreatment library ART" using a
      planning library based on the three planning CTs; and the "Evolutive library
      ART", which was the "Pretreatment library ART" strategy enriched by including
      some CBCT anatomies into the library when the daily clinical target volume (CTV)
      shape differed from the ones in the library. Two planning target volume (PTV)
      margins of 7 and 10 mm were evaluated. All the strategies were geometrically
      compared in terms of the percentage of coverage by the PTV, for the CTV and the
      organs at risk (OAR) delineated on the CBCT. Inadequate coverage of the CTV and
      OARs by the PTV was also assessed using deformable image registration. The
      cumulated dose distributions of each strategy were likewise estimated and
      compared for one patient. RESULTS: The "Evolutive library ART" strategy involved
      a number of added CBCTs: 0 for 55%; 1 for 30%; 2 for 5%; and 3 for 10% of
      patients. Compared with the other four, this strategy provided the highest CTV
      geometric coverage by the PTV, with a mean (min-max) coverage of 98.5% (96.4-100)
      for 10 mm margins and 96.2% (93.0-99.7) for 7 mm margins (P < 0.05). Moreover,
      this strategy significantly decreased the geometric coverage of the bowel. CTV
      undercoverage by PTV occurred in the anterior and superior uterine regions for
      all strategies. The dosimetric analysis at 7 mm similarly demonstrated that the
      "Evolutive library ART" increased the V42.75Gy of the CTV by 27%, 20%, 13%, and
      28% compared with "Standard RT", "ITV-based RT", "MidTtReplan", and "Pretreatment
      library ART", respectively. The dose to the bowel was also decreased by the
      "Evolutive library ART" compared with that by the other strategies. CONCLUSION:
      The "Evolutive library ART" is a personalized ART strategy that comprises a
      pretreatment planning library of three CT scans, enriched for half of the
      patients by one to three per-treatment CBCTs. This original strategy increased
      both the CTV coverage and bowel sparing compared with all the other tested
      strategies and enables us to consider a PTV margin reduction.

PMID- 29453894
TI  - Organisation of lymphocytic infiltrates in ANCA-associated glomerulonephritis.
AB  - AIMS: Renal involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis contributes to significant morbidity and mortality in patients. In
      chronic inflammation, B cells are recruited to the inflamed tissue and organised
      lymphoid structures have been described in several autoimmune diseases. The aim
      of this study was to correlate the lymphoid organisation in renal biopsies with
      renal outcome in ANCA-associated glomerulonephritis (GN). METHODS AND RESULTS: We
      investigated 112 renal biopsies from patients with newly diagnosed ANCA
      associated necrotising GN. We identified four different levels of the intrarenal
      organisation of lymphocytes: T cells without B cells, scattered B and T cells,
      clustered lymphocytic infiltrates and nodular compartmentally arranged B and T
      cell aggregates. Almost half the patients showed clusters of B and T lymphocytes
      in their biopsies. In 15 of these biopsies, a higher degree of organisation with
      lymphocytic compartments was detected. Inflammatory cell organisation was
      associated with renal failure, but not with tubular atrophy and interstitial
      fibrosis. Patients with organised lymphocytic infiltrates in their biopsy had
      worse renal function during follow-up and were more likely to develop end stage
      renal disease. CONCLUSIONS: In the present study, we show that the renal
      lymphocytic organisation is associated with renal outcome in ANCA-associated GN.
      The organisation of the lymphocytic infiltrate may be a morphological correlate
      of a perpetual and exaggerated inflammation in renal ANCA disease. Classifying
      the lymphocytic infiltrate could help to predict renal outcome, and might
      therefore be used for individualised adjustments in the intensity and duration of
      immunosuppressive therapy.

PMID- 29453895
TI  - Cross-sectional studies - what are they good for?
AB  - Cross-sectional studies serve many purposes, and the cross-sectional design is
      the most relevant design when assessing the prevalence of disease, attitudes and
      knowledge among patients and health personnel, in validation studies comparing,
      for example, different measurement instruments, and in reliability studies. This
      paper describes the use of cross-sectional studies and provides examples within
      obstetrics and gynecology. Caveats are also described; for example, when cross
      sectional data is used for analytical purposes of associations between an
      exposure and an outcome, authors and readers should be careful not to make causal
      inferences, unless the exposure may safely be assumed to be stable over time and
      not influenced by experiencing the outcome. In such cases, analyses are also
      subject to selection and information bias as well as confounding.

PMID- 29453896
TI  - Antimalarial drug mefloquine inhibits nuclear factor kappa B signaling and
      induces apoptosis in colorectal cancer cells.
AB  - Nuclear factor kappa B (NF-kappaB) signaling pathway is activated in many
      colorectal cancer (CRC) cells and in the tumor microenvironment, which plays a
      critical role in cancer initiation, development, and response to therapies. In
      the present study, we found that the widely used antimalarial drug mefloquine was
      a NF-kappaB inhibitor that blocked the activation of IkappaBalpha kinase, leading
      to reduction of IkappaBalpha degradation, decrease of p65 phosphorylation, and
      suppressed expression of NF-kappaB target genes in CRC cells. We also found that
      mefloquine induced growth arrest and apoptosis of CRC cells harboring
      phosphorylated p65 in culture and in mice. Furthermore, expression of
      constitutive active IKKbeta kinase significantly attenuated the cytotoxic effect
      of the compound. These results showed that mefloquine could exert antitumor
      action through inhibiting the NF-kappaB signaling pathway, and indicated that the
      antimalarial drug might be repurposed for anti-CRC therapy in the clinic as a
      single agent or in combination with other anticancer drugs.

PMID- 29453897
TI  - Is cidofovir a better treatment than imiquimod for high-grade vulval
      intraepithelial neoplasia?

PMID- 29453898
TI  - Post-paracentesis hemoperitoneum - Time to become more careful!

PMID- 29453901
TI  - Shedding light on aberrant interactions - a review of modern tools for studying
      protein aggregates.
AB  - The link between protein aggregation and neurodegenerative disease is well
      established. However, given the heterogeneity of species formed during the
      aggregation process, it is difficult to delineate details of the molecular events
      involved in generating pathological aggregates from those producing soluble
      monomers. As aberrant aggregates are possible pharmacological targets for the
      treatment of neurodegenerative diseases, the need to observe and characterise
      soluble oligomers has pushed traditional biophysical techniques to their limits,
      leading to the development of a plethora of new tools capable of detecting
      soluble oligomers with high precision and specificity. In this review, we discuss
      a range of modern biophysical techniques that have been developed to study
      protein aggregation, and give an overview of how they have been used to
      understand, in detail, the aberrant aggregation of amyloidogenic proteins
      associated with the two most common neurodegenerative disorders, Alzheimer's
      disease and Parkinson's disease.

PMID- 29453900
TI  - Downregulation of reticulocalbin-1 differentially facilitates apoptosis and
      necroptosis in human prostate cancer cells.
AB  - Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca2+ -binding
      protein, is dysregulated in cancers, but its pathophysiological roles are largely
      unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate
      cancer (PCa) samples, associated with cyclin B, not cyclin D1 expression,
      compared to that of benign tissues in a Chinese Han population. Downregulation of
      endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell
      cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1
      depletion causes ER stress, which is evidenced by induction of GRP78, activation
      of PERK and phosphorylation of eIF2alpha in PCa cells. Remarkably, RCN1 loss
      triggers DU145 cell apoptosis in a caspase-dependent manner but mainly causes
      necroptosis in LNCaP cells. An animal-based analysis confirms that RCN1 depletion
      suppresses cell proliferation and promotes cell death. Further investigations
      reveal that RCN1 depletion leads to elevation of phosphatase and tensin homolog
      (PTEN) and inactivation of AKT in DU145 cells. Silencing of PTEN partially
      restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation
      of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1
      may promote cell survival and serve as a useful target for cancer therapy.

PMID- 29453902
TI  - Peri-operative outcomes and complications after laparoscopic vs robot-assisted
      dismembered pyeloplasty: a systematic review and meta-analysis.
AB  - OBJECTIVE: To analyse the current difference between dismembered robot-assisted
      pyeloplasty (RAP) and laparoscopic pyeloplasty (LP) in the treatment of pelvi
      ureteric junction (PUJ) obstruction as of 26 June 2017, focusing on operating
      time, length of hospital stay, complication rate, and success rate. PATIENTS AND
      METHODS: We searched PubMed, Medline and Embase databases, consulted experts,
      reviewed reference lists, used the 'related articles' PubMed feature, and
      reviewed scientific meeting abstracts for eligible articles published between
      1993 and 26 June 2017. A modified Newcastle-Ottawa scale was used to assess study
      quality. Subgroup analyses were performed regarding patient age, single or
      multisurgeon experience, presence of complex renal anatomy, study quality,
      Clavien-Dindo grades, and length of follow-up. RESULTS: From 4101 identified
      articles, 17 studies meeting our eligibility criteria were included for data
      extraction. All were observational studies, with 10 deemed to be of low quality.
      Meta-analysis showed that RAP resulted in a 27-min shorter operating time
      (weighted mean difference [WMD] -26.71 min, 95% confidence interval [CI] -44.42
      to -9.00; P = 0.003) and a 1.2-day shorter length of hospital stay (WMD -1.21
      days, 95% CI -1.84 to -0.57; P = 0.003). The quality of evidence for these
      outcomes was rated as very low. Significant heterogeneity was found when
      analysing operating time (P < 0.001) and length of hospital stay (P < 0.001),
      which could not be fully explained through subgroup analyses. We also identified
      other potentially significant sources of bias for which we could not adjust our
      analysis. RAP was also associated with a lower complication rate (odds ratio [OR]
      0.56, 95% CI 0.37 to 0.84; P = 0.005) and higher success rate (OR 2.76, 95% CI
      1.30 to 5.88; P = 0.008); however, whether statistical advantages for these two
      outcomes translated into clinically significant advantages was unclear. The
      quality of evidence for these outcomes was rated as low. CONCLUSION: For patients
      with PUJ obstruction, our meta-analyses show that RAP is advantageous concerning
      operating time, length of hospital stay, complication rate and success rate. Our
      conclusions, however, are weakened by poor quality of evidence and significant
      study heterogeneity. In addition, whether the statistical significance observed
      in the present meta-analysis translates into clinical significance is an
      important question. Further high-quality studies, particularly randomized
      controlled trials, are necessary to strengthen conclusions.

PMID- 29453903
TI  - Tracking the Dynamic Folding and Unfolding of RNA G-Quadruplexes in Live Cells.
AB  - Because of the absence of methods for tracking RNA G-quadruplex dynamics,
      especially the folding and unfolding of this attractive structure in live cells,
      understanding of the biological roles of RNA G-quadruplexes is so far limited.
      Herein, we report a new red-emitting fluorescent probe, QUMA-1, for the
      selective, continuous, and real-time visualization of RNA G-quadruplexes in live
      cells. The applications of QUMA-1 in several previously intractable applications,
      including live-cell imaging of the dynamic folding, unfolding, and movement of
      RNA G-quadruplexes and the visualization of the unwinding of RNA G-quadruplexes
      by RNA helicase have been demonstrated. Notably, our real-time results revealed
      the complexity of the dynamics of RNA G-quadruplexes in live cells. We anticipate
      that the further application of QUMA-1 in combination with appropriate biological
      and imaging methods to explore the dynamics of RNA G-quadruplexes will uncover
      more information about the biological roles of RNA G-quadruplexes.

PMID- 29453899
TI  - The role of DNA-PK in aging and energy metabolism.
AB  - DNA-dependent protein kinase (DNA-PK) is a very large holoenzyme comprised of the
      p470 kDa DNA-PK catalytic subunit (DNA-PKcs ) and the Ku heterodimer consisting
      of the p86 (Ku 80) and p70 (Ku 70) subunits. It is best known for its
      nonhomologous end joining (NHEJ) activity, which repairs double-strand DNA
      (dsDNA) breaks (DSBs). As expected, the absence of DNA-PK activity results in
      sensitivity to ionizing radiation, which generates DSBs and defect in lymphocyte
      development, which requires NHEJ of the V(D)J region in the immunoglobulin and T
      cell receptor loci. DNA-PK also has been reported to have functions seemingly
      unrelated to NHEJ. For example, DNA-PK responds to insulin signaling to
      facilitate the conversion of carbohydrates to fatty acids in the liver. More
      recent evidence indicates that DNA-PK activity increases with age in skeletal
      muscle, promoting mitochondrial loss and weight gain. These discoveries suggest
      that our understanding of DNA-PK is far from complete. As many excellent reviews
      have already been written about the role of DNA-PK in NHEJ, here we will review
      the non-NHEJ role of DNA-PK with a focus on its role in aging and energy
      metabolism.

PMID- 29453904
TI  - Self-Assembly of Azobenzene Derivatives into Organogels and Photoresponsive
      Liquid Crystals.
AB  - A new class of coil-rod-coil molecules with an azobenzene core was synthesized.
      They were found to form robust organogels in several organic solvents. Scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), atomic force
      microscopy (AFM), FTIR spectroscopy, UV/Vis absorption spectroscopy, 1 H NMR
      spectroscopy, and X-ray diffraction (XRD) revealed that in these organogels, the
      molecules self-assembled into a nanofiber network with an H-type aggregation mode
      under the joint effect of pi-pi stacking, intermolecular hydrogen bonding, and
      van der Waals forces. Interestingly, the incorporation of the azobenzene mesogene
      into the rigid core led to photoisomerizable liquid crystal materials, which
      exhibited quick responsiveness to light and temperature, along with the trans-cis
      transition stimulated by UV light and heating.

PMID- 29453905
TI  - Sleep apnea and type 2 diabetes.
AB  - The aim of the present review was to clarify the association between obstructive
      sleep apnea (OSA) and type 2 diabetes, and discuss the therapeutic role of
      continuous positive airway pressure (CPAP) in type 2 diabetes. OSA patients are
      more likely than non-OSA populations to develop type 2 diabetes, while more than
      half of type 2 diabetes patients suffer from OSA. Similar to Western countries,
      in the East Asian population, the association between these two disorders has
      also been reported. CPAP is the primary treatment for OSA, but the effect of CPAP
      on comorbid diabetes has not been established. CPAP improved glucose metabolism
      determined by the oral glucose tolerance test in OSA patients, and several
      studies have shown that CPAP improves insulin resistance, particularly in obese
      populations undergoing long-term CPAP. Diabetes is associated with other sleep
      related manifestations as well, such as snoring and excessive daytime sleepiness.
      Snoring is associated with the development of diabetes, and excessive daytime
      sleepiness appears to modify insulin resistance. Well-designed studies are
      required to clarify the therapeutic effect of CPAP on diabetes. As both diabetes
      and OSA lead to cardiovascular disease, clinicians and healthcare professionals
      should be aware of the association between diabetes and OSA, and should take CPAP
      and health-related behaviors into consideration when treating patients with
      diabetes and/or OSA.

PMID- 29453906
TI  - Positive implications from socially accountable, community-engaged medical
      education across two Philippines regions.
AB  - INTRODUCTION: Hundreds of millions of people worldwide lack access to quality
      health services, largely because of geographic and socioeconomic maldistribution
      of qualified practitioners. This study describes differences between the practice
      locations of Philippines medical graduates from two 'socially accountable,
      community-engaged' health professional education (SAHPE) schools and the practice
      locations of graduates from two 'conventionally trained' medical schools located
      in the same respective geographic regions. Licensed medical graduates were
      currently practising in the Philippines and had been practising for at least 6
      months. Graduates were from two Philippines SAHPE schools (Ateneo de Zamboanga
      University-School of Medicine (ADZU-SOM) on the Zamboanga Peninsula (n=212) and
      the University of the Philippines Manila-School of Health Sciences (SHS-Palo) in
      Eastern Visayas (n=71), and from two 'conventional' medical schools Methods:
      Current graduate practice locations in municipalities or cities were linked with
      their respective population size and socioeconomic income class, and geocoded
      using Geographical Information System software onto a geospatial map of the
      Philippines. Bivariate analysis compared the population size and socioeconomic
      class of communities where the SAHPE medical graduates practised to communities
      where 'conventional' medical school graduates practised. RESULTS: Thirty-one
      percent of ADZU-SOM medical graduates practised in communities <100 000
      population versus 7% of graduates from the conventional school in the Zamboanga
      region (p<0.001), while 61% of SHS-Palo medical graduates practised in
      communities <100 000 population versus 12% of graduates from the conventional
      school in the Visayas region (p<0.001). Twenty-seven percent of ADZU-SOM
      graduates practised in lower income category communities (categories 2-6) versus
      8% of graduates from the conventional school in the same region (p<0.001), while
      49% of SHS-Palo graduates practised in lower income category communities
      (categories 2-6) versus 11% of graduates from the conventional school in the same
      region (p<0.001). CONCLUSIONS: SAHPE has contributed to increased medical
      coverage across rural and/or economically disadvantaged areas in two Philippines
      regions. The extensive community-based medical student placements associated with
      SAHPE likely play a significant role in graduates choosing to practice in rural
      and/or economically disadvantaged communities. Governments experiencing medical
      workforce maldistributions similar to those in the Philippines should consider
      SAHPE as a potentially cost-effective strategy in recruiting and retaining health
      graduates to underserved areas.

PMID- 29453907
TI  - Editorial: Multiple Sclerosis: Pathogenesis and Therapeutics.

PMID- 29453908
TI  - Effective anti-adhesives of uropathogenic Escherichia coli.
AB  - Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC)
      are among the most common infectious diseases in humans. Due to their frequent
      occurrence in the community and nosocomial settings, as well as the development
      of resistance to the commonly prescribed antimicrobial agents, an enormous
      financial burden is placed on healthcare systems around the world. Therefore,
      novel approaches to the prevention and treatment of UTIs are needed. Although
      UPEC may harbour a plethora of virulence factors, type I fimbriae and P pili are
      two of the most studied adhesive organelles, since the attachment to host cells
      in the urinary tract is a crucial step towards infection. Design of receptor
      analogues that competitively bind to UPEC surface adhesins placed at the top of
      pili organelles led to the development of anti-adhesive drugs that are
      increasingly recognized as important and promising alternatives to antibiotic
      treatment of UTIs.

PMID- 29453909
TI  - A headspace-gas chromatography method for isopropanol determination in warfarin
      sodium products as a measure of drug crystallinity.
AB  - Coumadin(r) a nd s everal generic products of warfarin s odium (WS) contain the
      crystalline form (clathrate) in which WS and isopropanol (IPA) are associated in
      a 2:1 molar ratio. IPA is critical in maintaining the WS crystalline structure.
      Physicochemical properties of the drug and drug product may change when the
      crystalline drug transforms to amorphous form. A headspace-gas chromatography (HS
      GC) method was developed and validated for IPA determination in the WS drug
      product. n-propanol (NPA) was used as internal standard and the method was
      validated for specificity, system suitability, linearity, accuracy, precision,
      range, limits of detection and quantification, and robustness. The method was
      specific, with good resolution between IPA and NPA peaks. Chromatographic
      parameters (retention time, IPA/NPA area ratio, tailing factor, theoretical
      plates, USP symmetry, capacity factor, selectivity and resolution) were
      consistent over three days of validation. The analytical method was linear from 2
      200 MUg mL-1 (0.1- 10 % IPA present in the drug product). LOD and LOQ were 0.1
      and 2 MUg mL-1, respectively. Accuracy at low (2 MUg mL-1) and high (200 MUg mL
      1) IPA concentrations of the calibration curve was 103.3-113.3 and 98.9-102.2 %
      of the nominal value, resp. The validated method was precise, as indicated by the
      RSD value of less than 2 % at three concentration levels of the calibration
      curve. The method reported here was utilized to determine accurately and
      precisely the IPA content in in-house formulations and commercial products. In
      summary, IPA determination by HS-GC provides an indirect measure of WS
      crystallinity in the drug product. Nevertheless, it should be confirmed by
      another analytical method since IPA from the drug substance is not
      distinguishable from IPA that may be present outside the drug crystals in a
      dosage form when prepared by wet granulation with IPA.

PMID- 29453910
TI  - Advanced spectrophotometric chemometric methods for resolving the binary mixture
      of doxylamine succinate and pyridoxine hydrochloride.
AB  - The prediction power of partial least squares (PLS) and multivariate curve
      resolution-alternating least squares (MCR-ALS) methods have been studied for
      simultaneous quantitative analysis of the binary drug combination - doxylamine
      succinate and pyridoxine hydrochloride. Analysis of first-order UV overlapped
      spectra was performed using different PLS models - classical PLS1 and PLS2 as
      well as partial robust M-regression (PRM). These linear models were compared to
      MCR-ALS with equality and correlation constraints (MCR-ALS-CC). All techniques
      operated within the full spectral region and extracted maximum information for
      the drugs analysed. The developed chemometric methods were validated on external
      sample sets and were applied to the analyses of pharmaceutical formulations. The
      obtained statistical parameters were satisfactory for calibration and validation
      sets. All developed methods can be successfully applied for simultaneous
      spectrophotometric determination of doxylamine and pyridoxine both in laboratory
      prepared mixtures and commercial dosage forms.

PMID- 29453911
TI  - Induction of xenobiotic-metabolizing enzymes in hepatocytes by beta
      naphthoflavone: Time-dependent changes in activities, protein and mRNA levels.
AB  - In the present study, time-dependency of the induction effect of a selective
      inducer on the activity, protein and mRNA levels of cytochromes P450 1A1/2
      (CYP1A1/2), NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S
      transferases (GSTA), in primary culture of rat hepatocytes was tested and
      evaluated. To show the differences in responses of tested enzymes, the common
      aryl hydrocarbon receptor (AhR) ligand agonist, beta-naphthoflavone (BNF), was
      used. Induction of CYP1A1/2 by BNF was detected at all time intervals and at all
      levels (i.e., mRNA, protein, enzyme activity). Different responses of NQO1 and
      GSTA upon BNF treatment were observed. Our results demonstrate that the responses
      of different xenobiotic-metabolizing enzymes to the inducer vary in time and
      depend on the measured parameter. For these reasons, an induction study featuring
      only one-time interval treatment and/ or one parameter testing could produce
      misleading information.

PMID- 29453912
TI  - HPTLC determination of diosgenin in fenugreek seeds.
AB  - A new HPTLC-densitometric method for diosgenin determination in fenugreek seeds
      was established after optimization of the conditions for efficient saponin
      extraction and acid hydrolysis. Several procedures were tested, the best of which
      was a three-step Soxhlet extraction, followed by hydrolysis of the obtained
      methanolic extract with 2 mol L-1 H2SO4. Best diosgenin separation from other
      hydrolysis products was obtained on HPTLC Si60F254 plates u sing a mixture of n
      heptane/ethyl acetate (7:3, V/V) and modified anisaldehyde as a spraying reagent.
      The method was preliminarily validated and the determined amounts of diosgenin in
      fenugreek seeds of Polish and African origin were found to be similar and ranged
      from 0.12-0.18 %.

PMID- 29453913
TI  - Chronic fluoxetine treatment induces lipid accumulation but does not alter the
      expression of Pref-1 in rat adipose tissue.
AB  - This study aims to investigate the effects of chronic fluoxetine (FLX) treatment
      on preadipocyte factor-1 (Pref-1) expression in subcutaneous, visceral and brown
      adipose tissues, and on the size of vacuoles in a dipocytes obtained from the
      perirenal regions in rats. Twenty-eight Wistar rats were treated with FLX at two
      different doses and fourteen animals received vehicle. After 40 days of
      treatment, the subcutaneous, perirenal and interscapular adipose tissues were
      collected. Pref-1 expression was examined using an immunohistochemical method and
      the vacuolar area was measured in stained sections. In the low dose FLX group,
      the size of vacuoles increased both in male and female animals. The high dose of
      FLX also induced a significant increase of vacuole size, but only in male
      animals. Neither of the two doses of FLX has significantly affected the Pref-1
      expression in any type of adipose tissue.

PMID- 29453914
TI  - Medication adherence and health-related quality of life among patients with
      chronic obstructive pulmonary disease.
AB  - This study evaluated medication adherence and health-related quality of life
      (HRQoL) of Slovenian patients with chronic obstructive pulmonary disease (COPD)
      and examined the factors associated with HRQoL. Demographic and therapy
      information was collected from 65 patients through interviews. The St. George's
      Respiratory Questionnaire and the Morisky Medication Adherence Scale were used to
      evaluate HRQoL and adherence, resp. A multiple linear regression model was used
      to assess the association between the factors and HRQoL. The mean St. George's
      Respiratory Questionnaire score (range 0-100, with higher scores indicating lower
      HRQoL) was 41.4. COPD affected patients' daily activities more than their social
      and psychological functioning. Slightly more than 53 % of the patients were
      optimally adherent, while 12 % were non-adherent. Patients with lower HRQoL had a
      larger number of medications for concomitant diseases, experienced COPD
      exacerbation in the last year, and had less education. No statistically
      significant correlation was found between medication adherence and HRQoL.

PMID- 29453915
TI  - Efficacy of nucleoside analogues for hepatitis B virus-related liver failure: A
      network meta-analysis.
AB  - The purpose of this study was to compare the efficacy of nucleoside analogues
      (NAs) in the treatment of HBV-related liver failure. The data of patients with
      HBV-related liver failure treated with nucleoside analogues were used to conduct
      a network meta-analysis. A total of 1660 patients from 12 articles about the
      efficacy of lamivudine, entecavir, telbivudine and tenofovir for HBV-related
      liver failure treatment were recruited in the study. The highest two- and three
      month survival rate was recorded for patients using tenofovir. The end-stage
      liver disease (MELD) score and mortality in patients undergoing tenofovir
      treatment were the lowest. Patients treated with telbivudine had the highest one
      month survival rate. Patients receiving enticavir therapy showed the lowest HBV
      DNA level. Our results indicate that tenofovir may be the best therapy for the
      treatment of HBV-related liver failure compared to other nucleoside analogues
      (including lamivudine, entecavir and telbivudine) and non-NAs treatment.

PMID- 29453916
TI  - Distinguishing Smilax glabra and Smilax china rhizomes by flow-injection mass
      spectrometry combined with principal component analysis.
AB  - Flow-injection mass spectrometry (FIMS) coupled with a chemometric method is
      proposed in this study to profile and distinguish between rhizomes of Smilax
      glabra (S. glabra) and Smilax china (S. china). The proposed method employed an
      electrospray-time-of-flight MS. The MS fingerprints were analyzed using principal
      component analysis (PCA) and orthogonal partial least squares discriminant
      analysis (OPLS-DA) with the aid of SIMCA software. Findings showed that the two
      kinds of samples perfectly fell into their own classes. Further predictive study
      showed desirable predictability and the tested samples were successfully and
      reliably identified. The study demonstrated that the proposed method could serve
      as a powerful tool for distinguishing between S. glabra and S. china.

PMID- 29453917
TI  - Comparative chemical investigation and evaluation of antioxidant and tyrosinase
      inhibitory effects of Withania somnifera (L.) Dunal and Solanum nigrum (L.)
      berries.
AB  - In the present study, berries of two different species of Solanaceae family,
      Withania somnifera (WS) and Solanum nigrum (SN), were extracted in methanol and
      then fractionated with solvents, ranging from non-polar to polar, for their
      phytochemical profiling and investigation of antioxidant and tyrosinase enzyme
      inhibition capacity. The methanolic extract and n-hexane, ethyl acetate (WSEA,
      SNEA) and aqueous fractions were chemically analyzed and evaluated for biological
      activity. Total flavonoids and total phenolics were quantified in WSEA (96.91 +/-
      1.56 MUg QE mg-1 sample and 178.45 +/- 2.78 MUg GAE mg-1 s ample, r esp.) and S
      NEA (89.58 +/- 0.98 MUg QE mg-1 sample and 120.15 +/- 2.33 MUg GAE mg-1 sample,
      resp.). HPLC-DAD analysis of ethyl acetate fractions of WS and SN measured 13.74
      and 5.34 MUg GAE mg-1 dry fraction and 3.72 and 3.41 MUg QE mg-1 dry fraction,
      resp. WSEA and SNEA fractions showed the highest 2,2-diphenyl-2-picryl hydrazyl
      (DPPH) radical scavenging, total antioxidant capacity and iron reducing power
      activity. The highest inhibition of tyrosinase enzyme was also exhibited by WSEA
      and SNEA (59.6 and 58.7 %) resp. This investigation justifies the medicinal value
      of W. somnifera and S. nigrum berry extracts as potential and readily available
      sources of natural antioxidants. Marked tyrosinase enzyme inhibition activity and
      antioxidant activity of both plant extracts might be due to polyphenols and
      flavonoids.

PMID- 29453918
TI  - High dose of histone deacetylase inhibitors affects insulin secretory mechanism
      of pancreatic beta cell line.
AB  - OBJECTIVE: Histone deacytylase inhibitors (HDACis) inhibit the deacetylation of
      the lysine residue of proteins, including histones, and regulate the
      transcription of a variety of genes. Recently, HDACis have been used clinically
      as anti-cancer drugs and possible anti-diabetic drugs. Even though HDACis have
      been proven to protect the cytokine-induced damage of pancreatic beta cells,
      evidence also shows that high doses of HDACis are cytotoxic. In the present
      study, we, therefore, investigated the eff ect of HDACis on insulin secretion in
      a pancreatic beta cell line. METHODS: Pancreatic beta cells MIN6 were treated
      with selected HDACis (trichostatin A, TSA; valproic acid, VPA; and sodium
      butyrate, NaB) in medium supplemented with 25 mM glucose and 13% heat-inactivated
      fetal bovine serum (FBS) for indicated time intervals. Protein expression of Pdx1
      and Mafa in MIN6 cells was demonstrated by immunohistochemistry and
      immunocytochemistry, expression of Pdx1 and Mafa genes was measured by
      quantitative RT-PCR method. Insulin release from MIN6 cells and insulin cell
      content were estimated by ELISA kit. Superoxide production in MIN6 cells was
      measured using a Total ROS/Superoxide Detection System. RESULTS: TSA, VPA, and
      NaB inhibited the expression of Pdx1 and Mafa genes and their products. TSA
      treatment led to beta cell malfunction, characterized by enhanced insulin
      secretion at 3 and 9 mM glucose, but impaired insulin secretion at 15 and 25 mM
      glucose. Th us, TSA induced dysregulation of the insulin secretion mechanism. TSA
      also enhanced reactive oxygen species production in pancreatic beta cells.
      CONCLUSIONS: Our results showed that HDACis caused failure to suppress insulin
      secretion at low glucose concentrations and enhance insulin secretion at high
      glucose concentrations. In other words, when these HDACis are used clinically,
      high doses of HDACis may cause hypoglycemia in the fasting state and
      hyperglycemia in the fed state. When using HDACis, physicians should, therefore,
      be aware of the capacity of these drugs to modulate the insulin secretory
      capacity of pancreatic beta cells.

PMID- 29453919
TI  - Genetic and epigenetic differences of benign and malignant pheochromocytomas and
      paragangliomas (PPGLs).
AB  - Pheochromocytomas and paragangliomas (PPGLs) are tumors arising from the adrenal
      medulla and sympathetic/parasympathetic paraganglia, respectively. According to
      Th e Cancer Genome Atlas (TCGA), approximately 40% of PPGLs are due to germ line
      mutations in one of 16 susceptibility genes, and a further 30% are due to somatic
      alterations in at least seven main genes (VHL, EPAS1, CSDE1, MAX, HRAS, NF1, RET,
      and possibly KIF1B). Th e diagnosis of malignant PPGL was straight forward in
      most cases as it was defined as presence of PPGL in non-chromaffin tissues.
      Accordingly, there is an extreme need for new diagnostic marker(s) to identify
      tumors with malignant prospective. Th e aim of this study was to review all
      suggested genetic and epigenetic alterations that are remarkably different
      between benign and malignant PPGLs. It seems that more than two genetic mutation
      clusters in PPGLs and other genetic and methylation biomarkers could be targeted
      for malignancy discrimination in different studies.

PMID- 29453920
TI  - Effect of trans-chalcone on hepatic IL-8 through the regulation of miR-451 in
      male rats.
AB  - OBJECTIVE: Trans-chalcone is a chalcone with hepatoprotective and anti
      inflammatory effects. However, the mechanism of these positive effects,
      especially on miR-451 as an inflammatory regulator, is poorly understood. In this
      regard, this microRNA (miRNA) acts by inhibition of hepatic interleukin-8 (IL-8)
      production in the liver which is one of the main proinflammatory cytokines. Th is
      study for the first time examined the effect of trans-chalcone on miR-451/IL-8
      pathway. METHODS: In present study, 21 male rats were randomly divided into 3
      groups (n=7 per each group): control which received solvent (NS), groups 2 (N2T)
      and 3 (N6T), which received transchalcone for 2 and 6 weeks, respectively.
      Hepatic level of miR-451 was measured by qRT-PCR. Serum levels of alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) as well as hepatic
      level of IL-8 protein were measured. RESULTS: Trans-chalcone decreased hepatic
      level of IL-8 protein and serum level of ALT aft er 2 weeks of treatment without
      significant change in hepatic miR-451. Moreover, it increased hepatic level of
      miR-451 and reduced hepatic IL-8 as well as AST and ALT aft er 6 weeks.
      CONCLUSION: Based on the results of present study, miR-451/IL-8 pathway is a
      possible mechanism for hepatoprotective action of trans-chalcone in long-term.

PMID- 29453921
TI  - Changes in erythrocyte deformability during day and possible role of melatonin.
AB  - OBJECTIVES: The deformability of erythrocytes is their ability to change shape in
      order to pass through the capillaries. Th is is necessary for quality of
      microcirculation and sufficient delivery of oxygen to the tissues. Th e aim of
      our study was to investigate the possible spontaneous changes in the erythrocyte
      deformability during day and evaluation of the possible direct effects of
      melatonin (hormone involved in regulation of biorhythms) on the erythrocyte
      deformability. METHODS: Samples of capillary blood were taken from 12 healthy
      volunteers in the morning (8:00) and early in the evening (16:30). Determination
      of erythrocyte deformability was done based on the measurement of their
      filtrability. It was measured immediately aft er the sample collection and 2-hour
      lasting incubation without or with melatonin (2000 MUmol/L). RESULTS: Erythrocyte
      deformability was significantly lower in the morning (filtrability index: 0.68+/
      0.01 morning vs. 0.71+/-0.01 early evening, p<0.05). Th e incubation of blood
      samples with melatonin did not have impact on deformability. CONCLUSIONS: We
      suggest the presence of diurnal changes in erythrocyte deformability with worse
      values in the morning that may contribute to higher risk of ischemic attacks in
      the morning hours. Direct in vitro effect of melatonin on deformability was not
      observed, but possible in vivo effects cannot be excluded.

PMID- 29453922
TI  - A short review of primary aldosteronism in a question and answer fashion.
AB  - OBJECTIVES: The aim of this study was to present up to date information
      concerning the diagnosis and treatment of primary aldosteronism (PA). PA is the
      most common cause of endocrine hypertension. It has been reported up to 24% of
      selective referred hypertensive patients. METHODS: We did a search in Pub-Med and
      Google Scholar using the terms: PA, hyperaldosteronism, idiopathic adrenal
      hyperplasia, diagnosis of PA, mineralocorticoid receptor antagonists,
      adrenalectomy, and surgery. We also did cross-referencing search with the above
      terms. We had divided our study into five sections: Introduction, Diagnosis,
      Genetics, Treatment, and Conclusions. We present our results in a question and
      answer fashion in order to make reading more interesting. RESULTS: PA should be
      searched in all high-risk populations. The gold standard for diagnosis PA is the
      plasma aldosterone/plasma renin ratio (ARR). If this test is positive, then we
      proceed with one of the four confirmatory tests. If positive, then we proceed
      with a localizing technique like adrenal vein sampling (AVS) and CT scan. If the
      lesion is unilateral, after proper preoperative preparation, we proceed, in
      adrenalectomy. If the lesion is bilateral or the patient refuses or is not fit
      for surgery, we treat them with mineralocorticoid receptor antagonists, usually
      spironolactone. CONCLUSIONS: Primary aldosteronism is the most common and a
      treatable case of secondary hypertension. Only patients with unilateral adrenal
      diseases are eligible for surgery, while patients with bilateral and non
      surgically correctable PA are usually treated by mineralocorticoid receptor
      antagonist (MRA). Thus, the distinction between unilateral and bilateral
      aldosterone hypersecretion is crucial.

PMID- 29453923
TI  - Magnesium upregulates insulin receptor and glucose transporter-4 in
      streptozotocin-nicotinamide-induced type-2 diabetic rats.
AB  - OBJECTIVE: We investigated the effects of magnesium supplementation on glucose
      tolerance, insulin sensitivity, oxidative stress as well as the concentration of
      insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide induced
      type-2 diabetic (T2D) rats. METHODS: Rats were divided into four groups
      designated as: 1) control (CTR); 2) diabetic untreated (DU); 3) diabetic treated
      with 1 mg of Mg/kg diet (Mg1-D); and 4) diabetic treated with 2 mg of Mg/kg diet
      (Mg2-D). T2D was induced with a single intraperitoneal (i.p.) injection of
      freshly prepared streptozotocin (55 mg/kg) aft er an initial i.p. injection of
      nicotinamide (120 mg/kg). Glucose tolerance, insulin sensitivity, lipid profile,
      malondialdehyde (MAD) and glutathione content, insulin receptors (INSR) and
      glucose transporter-4 (GLUT4), fasting insulin and glucose levels were measured,
      and insulin resistance index was calculated using the homeostatic model
      assessment of insulin resistance (HOMA-IR). RESULTS: Magnesium supplementation
      improved glucose tolerance and lowered blood glucose levels almost to the normal
      range. We also recorded a noticeable increase in insulin sensitivity in Mg-D
      groups when compared with DU rats. Lipid perturbations associated T2D were
      significantly attenuated by magnesium supplementation. Fasting glucose level was
      comparable to control values in the Mg-D groups while the HOMA-IR index was
      significantly lower compared with the DU rats. Magnesium reduced MDA but
      increased glutathione concentrations compared with DU group. Moreover, INSR and
      GLUT4 levels were elevated following magnesium supplementation in T2D rats.
      CONCLUSION: These findings demonstrate that magnesium may mediate effective
      metabolic control by stimulating the antioxidant defense, and increased levels of
      INSR and GLUT4 in diabetic rats.

PMID- 29453924
TI  - The World Health Organization (WHO) versus The International Association of
      Diabetes and Pregnancy Study Group (IADPSG) diagnostic criteria of gestational
      diabetes mellitus (GDM) and their associated maternal and neonatal outcomes.
AB  - Background Gestational diabetes mellitus (GDM) is a common medical complication
      in pregnancy. The aim of this study was to compare the prevalence of GDM using
      the World Health Organization (WHO) criteria and the International Association of
      Diabetes and Pregnancy Study Group (IADPSG) criteria in our population. We
      further compared the incidence of adverse maternal and neonatal outcomes in women
      diagnosed with GDM using these criteria and determined whether the IADPSG
      criteria is suitable in our population. Methods This randomized controlled trial
      was conducted at our antenatal clinic involving 520 patients from 1st February
      2015 until 30th September 2017. They were randomized into the WHO and the IADPSG
      groups. All eligible women underwent a standard oral glucose tolerance test with
      75 g glucose, their fasting and 2 h post prandial glucose levels were taken. The
      primary outcome was the prevalence of GDM. The secondary outcomes were the
      incidence of primary cesarean section, gestational hypertension or preeclampsia,
      preterm delivery <37 weeks, fetal macrosomia, neonatal hypoglycemia and shoulder
      dystocia or birth injury. Results The prevalence of GDM in both groups were
      similar (37.9% vs. 38.6%). GDM women in the WHO group had a significantly higher
      incidence of gestational hypertension or preeclampsia (p = 0.004) and neonatal
      hypoglycemia (p = 0.042). In contrast, GDM women in the IADPSG group had a
      significantly higher incidence of fetal macrosomia (p = 0.027) and cesarean
      section (p = 0.012). Conclusion The IADPSG diagnostic criteria for GDM may not be
      suitable for use in our population as it resulted in women being diagnosed later
      and being undertreated, thus leading to adverse maternal and neonatal outcomes.

PMID- 29453925
TI  - Impact of opioid therapy on gonadal hormones: focus on buprenorphine.
AB  - Objective The USA is in the midst of an opioid crisis. Understanding the impact
      of opioids and commonly used treatments for opioid dependence is essential for
      clinicians and researchers in order to educate and treat the nation's growing
      population with opioid use disorders. As a relatively new treatment for opioid
      dependence, buprenorphine is gaining popularity to the extent of becoming not
      only a preferred approach to the maintenance of opiate addiction, but also an
      option for chronic pain management. The purpose of this report is to review the
      available evidence on the endocrine effects of buprenorphine, particularly as it
      relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial
      and not fully defined. Method We conducted a Pubmed search (2000-2017) for human
      studies in the English language for articles that were available as full length
      regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids.
      Case reports were also reviewed, although prospective studies and randomized
      controlled trials received more weight. Results Opioid induced hypogonadism is
      well established. Most studies report that buprenorphine being a partial
      agonist/antagonist may not be impacting the pituitary trophic hormones as much.
      There are reports of sexual dysfunction in subjects maintained on buprenorphine,
      some without hormonal correlation. Thus with the understanding that pertinent
      clinical studies are limited in number, varied in methodology, mostly cross
      sectional, predominantly in men and small number of participants, more research
      in this area is warranted. Conclusion Based on a comprehensive review of the
      available literature, we conclude that despite its increasing popularity,
      buprenorphine has not been adequately studied in respect to its long-term effects
      on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for
      longitudinal systematic trials to define the potential buprenorphine-induced
      endocrine consequences.

PMID- 29453926
TI  - Sleep disorder prevalence in at-risk adolescents and potential effects of
      nightmare triad syndrome.
AB  - Objective At-risk high school students, those considered to have a higher
      probability for academic failure or dropping out, were assessed for various sleep
      disorders. Effects were compared between students with and without the nightmare
      triad syndrome (NTS+), the sleep disorders' cluster of frequent nightmares,
      insomnia disorder and suspected sleep-disordered breathing (SDB). Methods Data
      were gathered at a charter school for at-risk youth using: computer based
      surveys, physical airway exams, and mental health interviews by school social
      worker. Ninety-two students were enrolled, and 70 completed all study components.
      Results Students were teenaged [17.10 (1.50) years], male (52.2%) slightly
      overweight [BMI 25.50 (6.41)] Hispanics (87.0%); two-thirds (65 of 92)
      subjectively reported a sleep problem. Frequent nightmares (39.1%), insomnia (ISI
      >= 12, 41.3%), and SDB risk (79.3%) were common. Several presumptive sleep
      disorders (insomnia, SDB risk, parasomnia, or nightmares) were associated with
      worse sleep quality and lower quality of life. Nineteen students met criteria for
      NTS. Compared to NTS-, NTS+ showed significantly lower quality of life (p <
      0.003, g = 0.84). Regression analyses revealed higher levels of depression and
      anxiety symptoms in NTS+ students. NTS was associated with reduced quality of
      life independent of anxiety symptoms. Conclusion Prevalence of presumptive sleep
      disorders was high with a tendency for clusters of sleep disorders in the same
      individual. Students with NTS+ showed worse outcomes and reduced quality of life,
      mediated partially by depression and anxiety. To examine relationships between
      sleep disorders and mental health in at-risk adolescents, research investigations
      must include both subjective and objective measurements of sleep.

PMID- 29453927
TI  - Effect of prenatal recommendations of Traditional Persian Medicine on obstetric
      outcomes: a randomized clinical trial.

PMID- 29453928
TI  - CD4+CD25+CD127low FoxP3+ regulatory T cells in Crohn's disease.
AB  - BACKGROUND: Regulatory T (Treg) cell plays a key role in autoimmune diseases. We
      evaluated the regulatory function and frequency of Treg cells and secreted IL-10,
      IL-35 concentration in Crohn's disease (CD). METHODS: Twenty-three patients with
      CD and 25 healthy controls (HC) were included in this study. We analysed the
      alteration of Tregs frequency using flow cytometry for CD4, CD25, CD127 and FoxP3
      markers. Surface expression of CD4, CD25 and CD127 markers were used for
      isolation of relatively pure Treg cells. Suppressive activity of Tregs was
      determined by measuring their ability to inhibit the proliferation of T responder
      (Tres) cells. In addition, the amounts of IL-10 and IL-35 cytokines in co-culture
      supernatants were measured by ELISA assay after stimulation with anti
      CD2/CD3/CD28. RESULTS: CD patients had significantly lower frequency of CD4+
      CD25+ CD127low FoxP3+ Treg cells in comparison with controls (2.17 +/- 1.04 vs.
      2.83 +/- 1.07, p = 0.0352). Additionally, Treg cells mediated suppression was not
      significantly different in CD patients compared to controls. There was a
      significant difference in IL-10 secretion in response to anti-CD2/CD3/CD28
      stimulation compared with HC (p = 0.0074). CONCLUSION: The frequency of CD4+
      CD25+ CD127low FoxP3+ Tregs decreased in active stage of CD but there was no
      impaired suppressive function of CD4+ CD25+ CD127low FoxP3+ Treg cells. We
      suggest that an alteration in the balance of Tregs and T effectors may contribute
      to pathogenesis of CD.

PMID- 29453929
TI  - The diagnostic and prognostic value of serum endocan in patients with cirrhotic
      cardiomyopathy.
AB  - BACKGROUND: We aimed to determine the relationship between endocan and cirrhotic
      cardiomyopathy. MATERIALS AND METHODS: Patients with liver cirrhosis and no heart
      disease were included in a prospective observational study with liver disease
      decompensation and death as primary outcomes. RESULTS: 83 cirrhotic patients were
      included and 32 had cirrhotic cardiomyopathy. Endocan levels were significantly
      lower in patients with cirrhotic cardiomyopathy (5.6 vs. 7 ng/mL, p = 0.034).
      Endocan correlated with severity of cirrhosis, time to decompensation or death
      from liver disease (OR 4.5 95% CI 1.06-31.1). CONCLUSION: Endocan is a promising
      biomarker of severity of cirrhosis and may help in the diagnosis of cardiac
      dysfunction in this population.

PMID- 29453930
TI  - Ensemble survival tree models to reveal pairwise interactions of variables with
      time-to-events outcomes in low-dimensional setting.
AB  - Unraveling interactions among variables such as genetic, clinical, demographic
      and environmental factors is essential to understand the development of common
      and complex diseases. To increase the power to detect such variables interactions
      associated with clinical time-to-events outcomes, we borrowed established
      concepts from random survival forest (RSF) models. We introduce a novel RSF-based
      pairwise interaction estimator and derive a randomization method with bootstrap
      confidence intervals for inferring interaction significance. Using various linear
      and nonlinear time-to-events survival models in simulation studies, we first show
      the efficiency of our approach: true pairwise interaction-effects between
      variables are uncovered, while they may not be accompanied with their
      corresponding main-effects, and may not be detected by standard semi-parametric
      regression modeling and test statistics used in survival analysis. Moreover,
      using a RSF-based cross-validation scheme for generating prediction estimators,
      we show that informative predictors may be inferred. We applied our approach to
      an HIV cohort study recording key host gene polymorphisms and their association
      with HIV change of tropism or AIDS progression. Altogether, this shows how linear
      or nonlinear pairwise statistical interactions of variables may be efficiently
      detected with a predictive value in observational studies with time-to-event
      outcomes.

PMID- 29453931
TI  - Comparison of Return to Pre-Injury Sport After 10 mm Size Bone-Patellar Tendon
      Bone (BPTB) versus 8 mm Hamstring Anterior Cruciate Ligament Reconstruction: A
      Retrospective Study with a Two-Year Follow-Up.
AB  - BACKGROUND The aim of this study was to evaluate the reconstruction of a torn
      anterior cruciate ligament (ACL) with 10 mm diameter BPTB (bone-patellar tendon
      bone) autograft versus 8 mm HT (hamstring tendon) autografts, to compare the
      ability to restore pre-injury sports activities and reduce revision risk after
      these procedures. MATERIAL AND METHODS A prospective clinical review was
      performed to compare results of patients who underwent primary anatomical ACLR
      with 10 mm BPTB autografts with patients who underwent 8 mm diameter HT
      autografts, between January 2011 and January 2014. RESULTS There were 183
      patients evaluated: the 8 mm HT group showed statistically significant higher
      knee laxity values compared to the 10 mm BPTB group (p=0.042), and significant
      difference were detected in subjective International Knee Documentation Committee
      (IKDC) evaluation scores; the average subjective IKDC evaluations after two-year
      follow-up in the HT group was 88.45+/-2.8 versus 89.24+/-2.5 in BPTB group
      (p=0.047). In the evaluation of the IKDC objective protocol, results were
      excellent and good in 83 patients (94.3%) after BPTB and in 78 patients (82%)
      after HT ACLR (p<0.05). The average score on the Tegner activity scale in the HT
      group decreased from 6.5 at pre-injury to 5.8 at two-year follow-up (p<0.001) and
      from 6.7 at pre-injury to 6.5 at two-year follow-up in the BPTB group (p=0.4).
      The ability to restore pre-injury sports activities was higher in the BPTB group
      (6.5) versus the HT group (5.8) (p<0.001). Revision was required for two patients
      (2.2%) in the BPTB group compared with 14 patients (14.7%) in the HT group
      (p<0.05). CONCLUSIONS Smaller HT graft size was a predictor of higher knee laxity
      and greater revision risk at two-year post primary ACL reconstruction. Larger
      diameter BPTB ACL grafts had a better ability to restore knee stability and
      greater ability to restore pre-injury sports activities.

PMID- 29453932
TI  - Neurotrophin-3 restores synaptic plasticity in the striatum of a mouse model of
      Huntington's disease.
AB  - AIMS: Neurotrophin-3 (NT-3) is expressed in the mouse striatum; however, it is
      not clear the NT-3 role in striatal physiology. The expression levels of mRNAs
      and immune localization of the NT-3 protein and its receptor TrkC are altered in
      the striatum following damage induced by an in vivo treatment with 3
      nitropropionic acid (3-NP), a mitochondrial toxin used to mimic the
      histopathological hallmarks of Huntington's disease (HD). The aim of this study
      was to evaluate the role of NT-3 on corticostriatal synaptic transmission and its
      plasticity in both the control and damaged striatum. METHODS: Corticostriatal
      population spikes were electrophysiologically recorded and striatal synaptic
      plasticity was induced by high-frequency stimulation. Further, the
      phosphorylation status of Trk receptors was tested under conditions that imitated
      electrophysiological experiments. RESULTS: NT-3 modulates both synaptic
      transmission and plasticity in the striatum; nonetheless, synaptic plasticity was
      modified by the 3-NP treatment, where instead of producing striatal long-term
      depression (LTD), long-term potentiation (LTP) was obtained. Moreover, the
      administration of NT-3 in the recording bath restored the plasticity observed
      under control conditions (LTD) in this model of striatal degeneration.
      CONCLUSION: NT-3 modulates corticostriatal transmission through TrkB stimulation
      and restores striatal LTD by signaling through its TrkC receptor.

PMID- 29453933
TI  - Myt1l induced direct reprogramming of pericytes into cholinergic neurons.
AB  - OBJECTIVE: The cholinergic deficit is thought to underlie progressed cognitive
      decline in Alzheimer Disease. The lineage reprogramming of somatic cells into
      cholinergic neurons may provide strategies toward cell-based therapy of
      neurodegenerative diseases. METHODS AND RESULTS: Here, we found that a
      combination of neuronal transcription factors, including Ascl1, Myt1l, Brn2,
      Tlx3, and miR124 (5Fs) were capable of directly converting human brain vascular
      pericytes (HBVPs) into cholinergic neuronal cells. Intriguingly, the inducible
      effect screening of reprogramming factors showed that a single reprogramming
      factor, Myt1l, induced cells to exhibit similarly positive staining for Tuj1,
      MAP2, ChAT, and VAChT upon lentivirus infection with the 5Fs after 30 days. HBVP
      converted neurons were rarely labeled even after long-term incubation with BrdU
      staining, suggesting that induced neurons were directly converted from HBVPs
      rather than passing through a proliferative state. In addition, the
      overexpression of Myt1l induced the elevation of Ascl1, Brn2, and Ngn2 levels
      that contributed to reprogramming. CONCLUSIONS: Our findings provided proof of
      the principle that cholinergic neurons could be produced from HBVPs by
      reprogramming factor-mediated fate instruction. Myt1l was a critical mediator of
      induced neuron cell reprogramming. HBVPs represent another excellent alternative
      cell resource for cell-based therapy to treat neurodegenerative disease.

PMID- 29453936
TI  - A new method for the rapid characterization of root growth and distribution using
      digital image correlation.
AB  - Rapidly determining root growth patterns is biologically important and
      technically challenging. Current methods focus on direct observation of roots and
      require destructive excavations or time-consuming root tracing. We developed a
      novel methodology based on analyzing soil particle displacement, rather than
      direct observation of roots. This inferred root growth method uses digital image
      correlation (DIC) analysis, an established and high-throughput method used in
      many engineering and science disciplines. By applying DIC analyses to repeated
      images of plants grown in clear window boxes, we produced visually intuitive and
      quantifiable strain maps, indicating the magnitude and direction of soil
      movement. From this, we could infer root growth and rapidly quantify root system
      metrics. Strain measures were closely associated with the spatial distribution of
      roots and correlated with root length measured using conventional approaches. The
      method also allowed for the detection of root proliferation in nutrient-enriched
      soil patches, indicating its suitability for quantifying biological patterns.
      This novel application of DIC in root biology is effective, scalable, low cost,
      flexible and complementary to existing technologies. This method offers a new
      tool for answering questions in plant biology and will be particularly useful in
      studies involving temporal dynamics of root processes.

PMID- 29453935
TI  - Evaluation of cerebrospinal fluid phosphorylated tau231 as a biomarker in the
      differential diagnosis of Alzheimer's disease and vascular dementia.
AB  - BACKGROUND: The diagnosis of either Alzheimer's disease (AD) or vascular dementia
      (VaD) is still largely based on clinical guidelines and exclusion of other
      diseases that may lead to dementia. AIMS: In this study, we assessed whether the
      use of sensitive and specific biomarkers such as phosphorylated tau proteins
      could contribute to an earlier and more accurate diagnosis of AD and VaD, as well
      as to their differentiation. MATERIAL AND METHODS: A total of 198 patients, of
      which 152 had AD, 28 VaD, and 18 were healthy controls (HC), were included in the
      analyses. We analyzed cerebrospinal fluid (CSF) levels of total tau protein (t
      tau), tau protein phosphorylated at threonine 231 (p-tau231), and factor score
      (FS) determined by combination of p-tau231 and Mini-Mental State Examination
      (MMSE) in patients with AD and VaD, as well as in HC. We tested the diagnostic
      accuracy of these biomarkers in the CSF and FS (p-tau231, MMSE) in
      differentiating AD from VaD and HC. RESULTS: Total tau levels were significantly
      elevated in subjects with AD compared to HC, as well as in VaD subjects compared
      to HC. DISCUSSION: p-tau231 levels were significantly higher in patients with
      ADvsHC as well in patients with VaD vsHC. p-tau231 levels did not distinguish AD
      from VaD patients. Importantly, FS(p-tau231 and MMSE) showed statistically
      significant differences in the distribution of subjects with AD and VaD.
      CONCLUSION: These results indicate that FS (p-tau231 and MMSE) has a strong
      potential to provide an early distinction between AD and VaD.

PMID- 29453934
TI  - Distinct domains of the AVRPM3A2/F2 avirulence protein from wheat powdery mildew
      are involved in immune receptor recognition and putative effector function.
AB  - Recognition of the AVRPM3A2/F2 avirulence protein from powdery mildew by the
      wheat PM3A/F immune receptor induces a hypersensitive response after co
      expression in Nicotiana benthamiana. The molecular determinants of this
      interaction and how they shape natural AvrPm3a2/f2 allelic diversity are unknown.
      We sequenced the AvrPm3a2/f2 gene in a worldwide collection of 272 mildew
      isolates. Using the natural polymorphisms of AvrPm3a2/f2 as well as sequence
      information from related gene family members, we tested 85 single-residue-altered
      AVRPM3A2/F2 variants with PM3A, PM3F and PM3FL456P/Y458H (modified for improved
      signaling) in Nicotiana benthamiana for effects on recognition. An intact
      AvrPm3a2/f2 gene was found in all analyzed isolates and the protein variant
      recognized by PM3A/F occurred globally at high frequencies. Single-residue
      alterations in AVRPM3A2/F2 mostly disrupted, but occasionally enhanced, the
      recognition response by PM3A, PM3F and PM3FL456P/Y458H . Residues enhancing
      hypersensitive responses constituted a protein domain separate from both
      naturally occurring polymorphisms and positively selected residues of the gene
      family. These results demonstrate the utility of using gene family sequence
      diversity to screen residues for their role in recognition. This approach
      identified a putative interaction surface in AVRPM3A2/F2 not polymorphic in
      natural alleles. We conclude that molecular mechanisms besides recognition drive
      AvrPm3a2/f2 diversification.

PMID- 29453937
TI  - Trajectory classes of cannabis use and heavy drinking among rural African
      American adolescents: multi-level predictors of class membership.
AB  - AIMS: To inform research on the etiology and prevention of substance use among
      rural African American youth by (a) identifying developmental trajectory classes
      of cannabis use and heavy drinking across adolescence and young adulthood and (b)
      examining associations between trajectory class membership and multi-level
      assessments of risk factors. DESIGN: A prospective study spanning 9 years with
      assessments of cannabis use and heavy drinking, the catecholamines epinephrine
      and norepinephrine, perceived stress and psychosocial risk factors. SETTING:
      Rural communities in the southeastern United States. PARTICIPANTS: African
      American youth (n = 518). MEASUREMENTS: Participants were assessed for cannabis
      use and heavy drinking at seven assessments beginning at 16 years of age and
      continuing to 25 years of age. At age 19, participants provided overnight urine
      voids that were assayed for catecholamines, a biological marker of life stress
      resulting from sympathetic nervous system activation. At ages 16 and 19,
      participants provided information on malleable psychosocial risk factors.
      FINDINGS: Latent class growth models revealed three distinct trajectory classes
      for cannabis use and for heavy drinking. Higher levels of circulating stress
      hormones and perceived stress were associated with classes reporting greater
      substance use over time (all Ps < 0.05). A composite of selected risk factors
      discriminated class membership (all Ps < 0.05). Trajectory classes characterized
      by rapid usage increases in early adulthood exhibited the greatest increase in
      deviant peer affiliations between ages 16 and 19 years. CONCLUSIONS: Rural
      African American youth's cannabis use and heavy drinking across adolescence and
      young adulthood demonstrate distinct developmental courses; a small number of
      risk factors and measures of biological and perceived stress differentiate class
      membership prognostically. Variability over time in these measures, specifically
      an increase in deviant peer affiliation, may help to account for steep increases
      in young adulthood.

PMID- 29453938
TI  - Barley stripe mosaic virus infection requires PKA-mediated phosphorylation of
      gammab for suppression of both RNA silencing and the host cell death response.
AB  - The Barley stripe mosaic virus (BSMV) gammab protein is a viral suppressor of RNA
      silencing (VSR) and symptom determinant. However, it is unclear how post
      translational modification affects the different functions of gammab. Here, we
      demonstrate that gammab is phosphorylated at Ser-96 by a PKA-like kinase in vivo
      and in vitro. Mutant viruses containing a nonphosphorylatable substitution
      (BSMVS96A or BSMVS96R ) exhibited reduced viral accumulation in Nicotiana
      benthamiana due to transient induction of the cell death response that
      constrained the virus to necrotic areas. By contrast, a BSMVS96D mutant virus
      that mimics gammab phosphorylation spread similarly to the wild-type virus.
      Furthermore, the S96A mutant had reduced local and systemic gammab VSR activity
      due to having compromised its binding activity to 21-bp dsRNA. However,
      overexpression of other VSRs in trans or in cis failed to rescue the necrosis
      induced by BSMVS96A , demonstrating that suppression of cell death by gammab
      phosphorylation is functionally distinct from its RNA silencing suppressor
      activities. These results provide new insights into the function of gammab
      phosphorylation in regulating RNA silencing and the BSMV-induced host cell death
      response, and contribute to our understanding of how the virus optimizes the
      balance between viral replication and virus survival in the host plants during
      virus infection.

PMID- 29453939
TI  - Editorial: Spatial Cognition in Normal Aging, MCI and AD.

PMID- 29453940
TI  - A Refractory Cutaneous Abscess.

PMID- 29453941
TI  - Increased Morbidity and Mortality Associated with Falls Among Patients with
      Cirrhosis.
AB  - BACKGROUND: Injuries are more morbid and complicated to manage in patients with
      cirrhosis. However, data are limited regarding the relative risk of injury and
      severity of injury from falls in patients with cirrhosis compared with those
      without cirrhosis. METHODS: We examined the nationally representative National
      Emergency Department Sample, an all-payer database including all patients
      presenting with falls, 2009-2012. We determined the relative risks for and
      clinical associations with severe injuries. Outcomes included hospitalization,
      length of stay, costs, and in-hospital death. Outcomes were compared with those
      of patients with congestive heart failure. RESULTS: We identified 102,977 visits
      involving patients with cirrhosis and 26,996,120 involving patients without
      cirrhosis who presented with a fall. Overall and compared with patients with
      congestive heart failure, the adjusted risk of severe injury was higher for
      patients with cirrhosis. These included intracranial hemorrhage (2.33; 95%
      confidence interval [CI], 2.02-2.68), skull fracture (1.75; 95% CI, 1.53-2.00),
      and pelvic fracture (1.71; 95% CI, 1.56-1.88). Risk was lower for less-severe
      injuries, such as concussion (0.95; 95% CI, 0.86-1.06) and lower-leg fracture
      (0.86; 95% CI, 0.80-0.91). Risk factors significantly positively associated with
      severe injury on multivariate analysis were hepatic encephalopathy, alcohol
      abuse, and infection. Cirrhosis was associated with increased risk of in-hospital
      death, longer length of stay, and higher costs after a fall. All outcomes were
      worse compared with those for patients with congestive heart failure CONCLUSION:
      Falls are common in patients with cirrhosis, and they are more likely to incur
      severe injuries, with increased hospital costs and risk of death. Poor outcomes
      are most associated with ascites, hepatic encephalopathy, alcohol abuse, and
      infection, highlighting the subgroups at highest risk and most likely to benefit
      from preventative interventions.

PMID- 29453942
TI  - Mobile Thoracolithiasis.

PMID- 29453944
TI  - Clinical Features of Extrapulmonary Sarcoidosis Without Lung Involvement.
AB  - BACKGROUND: Compared with pulmonary sarcoidosis, sarcoidosis without lung
      involvement may involve other immunopathologic mechanisms and be associated with
      other demographic and clinical features. METHODS: This was a retrospective
      analysis of clinical data collected in real time on 1,686 patients with biopsy
      proven sarcoidosis from two large university sarcoidosis outpatient clinics in
      the United States. We compared differences in demographics characteristics and
      clinical presentation between pulmonary and nonpulmonary sarcoidosis (NPS).
      Patients were considered to have NPS only if they had normal chest imaging and no
      features consistent with pulmonary involvement on the basis of currently accepted
      criteria. RESULTS: A total of 8.3% of this sarcoidosis cohort met criteria for
      NPS. NPS was significantly more common in white than black patients, and more
      common in women than men. The skin was the most common organ involved, and was
      observed in nearly one-half of patients with NPS. Isolated skin sarcoidosis was
      the overwhelmingly most common pattern of organ involvement seen in the NPS group
      (25%), and no other pattern of involvement was found in more than 5% of patients
      with NPS. CONCLUSIONS: Significant demographic and sex differences were observed
      between patients with pulmonary and nonpulmonary sarcoidosis. These differences
      reflect previous data concerning differences between patients with skin and lung
      sarcoidosis because the skin was the major organ involved with NPS. Although the
      lungs are likely the primary site of exposure in pulmonary sarcoidosis, the high
      prevalence of skin involvement in NPS suggests the skin is the most conducive
      site of antigen capture outside of the respiratory tract.

PMID- 29453945
TI  - Evaluation of lipid peroxidation and antioxidant defense mechanisms in the bone
      of rats in conditions of separate and combined administration of vanadium (V) and
      magnesium (Mg).
AB  - The impact of vanadium (V) and magnesium (Mg) applied as sodium metavanadate
      (SMV, 0.125 mg V/ml) and magnesium sulfate (MS, 0.06 mg Mg/ml) on oxidative
      stress markers in bone of male Wistar rats was investigated. Some of them were
      also measured in the liver, e.g. l-ascorbic acid (hepatic L-AA). Additionally,
      relationships between selected indices determined in bone were examined. SMV
      alone (Group II) did not significantly alter the level of TBARS and the activity
      of SOD, compared with the control (Group I), but it slightly reduced the GR
      activity (by 13%) and the L-AA level (by 15.5%). It also markedly lowered the
      activity of CAT and GPx (by 34% and 29%), and to some degree elevated the
      activity of GST (by 16%) and the hepatic L-AA level (by 119%). MS alone (Group
      III) decreased the TBARS level (by 49%), slightly lowered the L-AA concentration
      (by 14%), and reduced the SOD, GPx, and GR activities (by 31%, 40%, and 28%), but
      did not change the activity of CAT, compared with the control. Additionally, it
      elevated the GST activity (by 56%) and the hepatic L-AA level (by 40%). In turn,
      the SMV + MS combination (Group IV) reduced the TBARS level (by 38%) and the SOD,
      CAT, GPx, and GR activities (by 61%, 58%, 72%, and 40%) but elevated the GST
      activity (by 66%), compared with the control. The activity of SOD and GPx in the
      rats in Group IV was also reduced, compared with Group II (by 61% and 61%) and
      Group III (by 44% and 54%). In turn, the activities of CAT and GR were decreased,
      compared with Group III (by 55%) and Group II (by 31%), and the L-AA level was
      lowered, in comparison with Groups II and III (by 53% and 54%). Further, the
      concentration of V in the bone of rats in Groups II and IV increased, whereas the
      concentration of Mg decreased, compared with Groups I and III, in which the V and
      Mg levels dropped and were not altered, respectively, compared with Group I. The
      total content of Fe in the bone of rats in Groups II and IV increased, compared
      with Group III, in which the total Fe content did not change, compared with Group
      I. In turn, the total bone Cu content significantly decreased in the rats in
      Groups III and IV, compared with Groups I and II, whereas the total Zn content
      and the Ca concentration did not change markedly. The results provided evidence
      that the concentration of V used as SMV did not enhance LPO in bone, whereas Mg,
      at the selected level, markedly reduced LPO in this tissue. On the other hand,
      both elements administered separately and in combination disrupted the
      antioxidant defense mechanisms and homeostasis of some metals in bone tissue,
      which consequently may have contributed to disturbances in the balance in the
      activities of osteoblastic and osteoclastic cells, and thereby negatively
      affected bone health.

PMID- 29453946
TI  - The sexual and reproductive health of foreign-born women in the United States.
AB  - OBJECTIVE: To explore the sexual and reproductive health (SRH) behaviors, health
      insurance coverage and use of SRH services of women in the United States (U.S.)
      by nativity, disaggregated by race and ethnicity. STUDY DESIGN: We analyzed
      publicly available and restricted data from the National Survey of Family Growth
      to assess differences and similarities between foreign-born and U.S.-born women,
      both overall and within Hispanic, non-Hispanic (NH) white, NH black and NH Asian
      groups. RESULTS: A larger proportion of foreign-born women than U.S.-born women
      lacked health insurance coverage. Foreign-born women utilized SRH services at
      lower rates than U.S.-born women; this effect diminished at the multivariate
      level, although race and ethnicity differences remained. Overall, foreign-born
      women were less likely to pay for SRH services with private insurance than U.S.
      born women. Foreign-born women were less likely to use the most effective
      contraceptive methods than U.S.-born women, with some variation across race and
      ethnicity: NH white and NH black foreign-born women were less likely to use
      highly effective contraceptive methods than their U.S.-born counterparts, but
      among Hispanic women, the reverse was true. CONCLUSION: Our findings demonstrate
      that the SRH behaviors, needs and outcomes of foreign-born women differ from
      those of U.S-born women within the same race/ethnic group. IMPLICATIONS: This
      paper contributes to the emergent literature on immigrants in the U.S. by laying
      the foundation for further research on the SRH of the foreign-born population in
      the country, which is critical for developing public health policies and programs
      to understand better and serve this growing and diverse population.

PMID- 29453947
TI  - Evaluation of the effects of RP5063, a novel, multimodal, serotonin receptor
      modulator, as single-agent therapy and co-administrated with sildenafil,
      bosentan, and treprostinil in a monocrotaline-induced pulmonary arterial
      hypertension rat model.
AB  - Pulmonary arterial hypertension (PAH), a condition that is defined by pulmonary
      vasculature constriction and remodeling, involves dysfunctional signaling of the
      serotonin (5-HT) receptors, 5-HT2A/2B/7. In a rat model of monocrotaline (MCT)
      induced PAH, the effectiveness of RP5063 (RP), a dopamine and 5-HT receptor
      modulator, was evaluated as monotherapy and as an adjunct to standard PAH
      treatments. After a single 60 mg/kg dose of MCT, rats received vehicle (MCT+Veh;
      gavage twice-daily [b.i.d.]), RP (10 mg/kg; gavage b.i.d.), bosentan (B; 100
      mg/kg; gavage BID), sildenafil (S; 50 mg/kg; gavage, BID), treprostinil (T; 100
      ng/kg/min over 24 h intravenous), RP+B, RP+S, and RP+T for 28 days. Single-agent
      RP limited the functional and structural effects of PAH seen in the MCT+Veh
      group, with significant improvements in pulmonary hemodynamics, right ventricular
      (RV) hypertrophy, SO2, and pulmonary blood vessel structural changes. These
      effects appeared comparable with those associated with B, S, and T. Adjunctive RP
      treatment resulted in significantly lower mean pulmonary arterial pressures, RV
      systolic pressure. It also improved SO2 measurements, as compared with MCT+Veh (P
      < 0.05), and diastolic pulmonary artery pressure (P < 0.05), as compared with
      single-agent B and S therapy (Bonferroni method adjusting for multiplicity). RP+S
      appeared to show the most consistent and extensive effects on pulmonary
      hemodynamics, respiratory parameters, and histopathologic changes. These results
      corroborate earlier preclinical findings supporting the efficacy of single-agent
      RP in PAH. RP, as mono and adjunctive therapy compared with induced-control,
      mitigated the functional and structural effects of MCT-induced PAH.

PMID- 29453949
TI  - Babesia bovis in and around Jimma town, Southwestern Ethiopia.

PMID- 29453948
TI  - Noncritical Signaling Role of a Kinase-Receptor Interaction Surface in the
      Escherichia coli Chemosensory Core Complex.
AB  - In Escherichia coli chemosensory arrays, transmembrane receptors, a histidine
      autokinase CheA, and a scaffolding protein CheW interact to form an extended
      hexagonal lattice of signaling complexes. One interaction, previously assigned a
      crucial signaling role, occurs between chemoreceptors and the CheW-binding P5
      domain of CheA. Structural studies showed a receptor helix fitting into a
      hydrophobic cleft at the boundary between P5 subdomains. Our work aimed to
      elucidate the in vivo roles of the receptor-P5 interface, employing as a model
      the interaction between E. coli CheA and Tsr, the serine chemoreceptor.
      Crosslinking assays confirmed P5 and Tsr contacts in vivo and their strict
      dependence on CheW. Moreover, the P5 domain only mediated CheA recruitment to
      polar receptor clusters if CheW was also present. Amino acid replacements at
      CheA.P5 cleft residues reduced CheA kinase activity, lowered serine response
      cooperativity, and partially impaired chemotaxis. Pseudoreversion studies
      identified suppressors of P5 cleft defects at other P5 groove residues or at
      surface-exposed residues in P5 subdomain 1, which interacts with CheW in
      signaling complexes. Our results indicate that a high-affinity P5-receptor
      binding interaction is not essential for core complex function. Rather, P5 groove
      residues are probably required for proper cleft structure and/or dynamic
      behavior, which likely impact conformational communication between P5 subdomains
      and the strong binding interaction with CheW that is necessary for kinase
      activation. We propose a model for signal transmission in chemotaxis signaling
      complexes in which the CheW-receptor interface plays the key role in conveying
      signaling-related conformational changes from receptors to the CheA kinase.

PMID- 29453943
TI  - MAPK and PI3K signaling: At the crossroads of neural crest development.
AB  - Receptor tyrosine kinase-mediated growth factor signaling is essential for proper
      formation and development of the neural crest. The many ligands and receptors
      implicated in these processes signal through relatively few downstream pathways,
      frequently converging on the MAPK and PI3K pathways. Despite decades of study,
      there is still considerable uncertainty about where and when these signaling
      pathways are required and how they elicit particular responses. This review
      summarizes our current understanding of growth factor-induced MAPK and PI3K
      signaling in the neural crest.

PMID- 29453950
TI  - Towards elimination of schistosomiasis after 5000 years of endemicity in Egypt.
AB  - Schistosomiasis is a snail-transmitted infectious disease caused by a long
      lasting infection with a blood fluke of the genus Schistosoma. S. haematobium and
      S. mansoni are the species endemic in Egypt. The country has been plagued and
      seriously suffered from schistosomiasis over the past 5000 years. Great strides
      had been done in controlling the disease since 1922. The history, epidemiology
      and the different control approaches were reviewed. Currently, Egypt is preparing
      towards schistosomiasis elimination by 2020. The new strategy depends on four
      main axes; large scale treatment in all areas of residual transmission by
      targeting entire populations with PZQ, intensified snail control, heath education
      and behavioral changes and expansion of the complementary public health
      interventions. While on the road towards elimination, we addressed here the
      important challenges, lessons and the key issues from the different control
      strategies to help the achievement of our goal. Notably, frangibility of the drug
      based control, emergence of resistance against PZQ, persistence of some hot spots
      areas, the need of further control efforts to the high risk individuals and
      community involvement in the control programs, reconsideration of diagnostic
      tests used in surveillance, and continous monitoring of the field to detect
      changes in the snail intermediate host. Importantly, the adaptation between the
      parasite and its intermediate snail host throughout water bodies in Egypt merits
      attention as Schistosoma infection can be introduced to the new reclaimed areas.
      This review may help supplying information for the policy makers to tailor
      control measures suitable to the local context that could help in the transfer
      from control to elimination.

PMID- 29453951
TI  - A new species of Simulium (Simulium) (Diptera: Simuliidae) from Genting
      Highlands, Malaysia.
AB  - Simulium (Simulium) rasuli sp. nov. is described from two females collected by a
      Malaise trap in Genting Highlands, Peninsular Malaysia. This new species is
      placed in the Simulium christophersi species-group of the subgenus Simulium. The
      female of this new specie is characterized by the scutum with three longitudinal
      vittae, dark legs, claw with a small subbasal tooth, and ovipositor valve
      triangular with its inner margin nearly straight. This new species is
      distinguished in the female from all the six named species of the species-group
      by the entirely brownish-black femora and tibiae.

PMID- 29453952
TI  - In Response.

PMID- 29453954
TI  - On "End-of-Life Decision Making for Parents of Extremely Preterm Infants".

PMID- 29453953
TI  - Concept Analysis of Responsible Sexual Behavior in Adult Women.
AB  - The concept of responsible sexual behavior is not clearly defined as it applies
      to adult women who have sex with men. Responsible sexual behavior is a socially
      desirable and deliberate pattern of behaviors used to promote sexual health,
      manage risk, and foster respect for sexual partners within the context of
      community influences. A purposeful redefinition may be necessary to maintain a
      concept that is useful and effective for evaluating sexual behavior.

PMID- 29453955
TI  - Cross-reactivity of anti-HMGB1 antibodies for HMGB2.
AB  - HMGB1 and HMGB2 are DNA-interacting proteins but can also have extracellular
      actions during inflammation. Despite their relatively high homology, they may
      have distinct roles, making it essential to be able to differentiate between the
      two. Here we examine the specificity of five commercially-available anti-HMGB1
      antibodies. By Western blotting of recombinant proteins and HMGB1-/- mouse
      embryonic fibroblasts, we identified only one HMGB1 antibody that, under our
      experimental conditions, did not also detect HMGB2. Selecting specific antibodies
      for HMGB1 and HMGB2 allowed identification of distinct HMGB1 and HMGB2
      subcellular pools in primary neutrophils.

PMID- 29453956
TI  - Frequent mutations of RetNet genes in eoHM: Further confirmation in 325 probands
      and comparison with late-onset high myopia based on exome sequencing.
AB  - In our previous study, potential pathological mutations of RetNet genes were
      detected in 23.8% (71/298) of probands with early-onset high myopia (eoHM), based
      on whole exome sequencing (WES). The current study aimed to confirm this finding
      in an additional 325 probands with eoHM and to clarify its specificity by
      comparison of 195 probands with late-onset high myopia (loHM). Variants in the
      234 RetNet genes were selected from whole-exome sequencing data and were filtered
      using multistep bioinformatics analyses. Potential pathological variants in 33
      genes were detected in 76 of 325 (23.4%) probands with eoHM and 14 of 195 (7.2%)
      probands with loHM. Thirty-five of the 76 (46.1%) probands with eoHM had
      mutations in COL2A1, COL11A1, RPGR, and CACNAIF, while only 2/14 (14.3%) probands
      with eoHM were detected. The mutation frequency and spectrum of RetNet genes in
      the 325 probands with eoHM were similar to our previous study but were
      significantly different in 195 probands with loHM (P = 2 * 10-6 and 0.04). Data
      from eoHM and loHM strongly suggest that a significant proportion of eoHM is
      caused by mutations in RetNet genes. These results also provide initial genetic
      evidence that eoHM is different from loHM. The presence of mutations in 7.2%
      probands with loHM raises questions about pathogenicity and the variable
      manifestation of some mutations. The functional studies of the mutations in
      question and more extensive investigations of related phenotypes in the mutation
      carriers and their family members may provide valuable information to address
      these questions.

PMID- 29453957
TI  - Automatic detection of the duration of visual static and dynamic stimuli.
AB  - The perception of the passing of time is fundamental to conscious experience. The
      duration of a sensory stimulus is one of its defining attributes, but it is not
      clear how this is encoded in the brain. This work explores whether the duration
      of a visual stimulus is an attribute that the brain can automatically adapt to
      and use to predict future stimulus durations. Visual mismatch negativity (vMMN)
      is an ERP component elicited, even when the stimuli are unattended, when an
      'unexpected' visual stimulus appears amongst a series of expected stimuli in an
      'oddball' paradigm. As such vMMN has been suggested to show that the violation of
      a pattern in a sequence has been automatically detected. To date, vMMN has only
      been measured to differences in the visual durations of static on/off stimuli,
      placed near to the centre of the visual field. Our study measures vMMN to test
      whether duration is encoded automatically for static stimuli against a blank
      background and moving stimuli against a static background, whilst attention is
      directed to a different spatial location using a continuous, attention demanding
      task. VMMN elicited in response to the shorter duration for both stimuli shows
      that the brain detects the differences of duration even in the absence of
      focussed spatial attention. For the motion stimulus a larger difference in
      duration was needed. We conclude that duration is encoded automatically in the
      visual cortex and is an attribute that can be adapted to, and form the basis of
      predictions.

PMID- 29453958
TI  - Age-dependent effects of dimethyl fumarate on cognitive and neuropathological
      features in the streptozotocin-induced rat model of Alzheimer's disease.
AB  - We previously demonstrated that dimethyl fumarate (DMF), an anti-oxidative and
      immunosuppresive compound, prevents intracerebroventricular (ICV) streptozotocin
      induced disruption of spatial memory and neurodegeneration in 4-month-old rats.
      The present study evaluated the influence of age on DMF's therapeutic effect.
      Aged rats (22-months-old, n = 40) were provided rodent chow containing DMF (0.4%)
      and given ICV injections of streptozotocin (STZ) or vehicle (Sham) on days 2 and
      4. Spatial memory was evaluated using the Morris water maze (MWM) on days 14-21.
      Hippocampal samples from young (4-month-old, n = 36, collected previously) and
      aged rats were assessed for presence of activated (CD68-positive) microglia, IL
      10 and oxidative/nitrative stress marker nitrotyrosine. Aged rat samples were
      also stained with Fluoro-JadeB marker for neurodegeneration. Previously obtained
      MWM and Fluoro-JadeB data from young rats served as a reference for assessing
      impact of age. Aged Sham DMF-fed rats exhibited better spatial memory and less
      neurodegeneration in the CA3 region of the hippocampus compared to corresponding
      young rats. Aged STZ rats displayed greater memory impairment and increased CA2
      neurodegeneration, CA1 nitrotyrosine immunoreactivity, and microglial activation
      in the dentate gyrus (DG), compared to young STZ rats. Notably, within aged STZ
      injected rats, DMF treatment was associated with improved performance in MWM,
      reduced neurodegeneration in all hippocampal areas, reduced DG microglia
      activation, and reduced CA1 nitrotyrosine labeling compared to age-matched rats
      without DMF treatment. This beneficial age-related effect of DMF treatment after
      STZ ICV injections may result from reduced microglial activation in the
      hippocampus that leads to an alleviation of oxidative stress, neurodegeneration,
      and memory impairments.

PMID- 29453959
TI  - Indices of repetitive behaviour are correlated with patterns of intrinsic
      functional connectivity in youth with autism spectrum disorder.
AB  - The purpose of the current study was to examine how repetitive behaviour in
      Autism Spectrum Disorder (ASD) is related to intrinsic functional connectivity
      patterns in a number of large-scale, neural networks. Resting-state fMRI scans
      from thirty subjects with ASD and thirty-two age-matched, typically developing
      control subjects were analysed. Seed-to-voxel and ROI-to-ROI functional
      connectivity analyses were used to examine resting-state connectivity in a number
      of cortical and subcortical neural networks. Bivariate correlation analysis was
      performed to examine the relationship between repetitive behaviour scores from
      the Repetitive Behaviour Scale - Revised and intrinsic functional connectivity in
      ASD subjects. Compared to control subjects, ASD subjects displayed marked over
      connectivity of the thalamus with several cortical sensory processing areas, as
      well as over-connectivity of the basal ganglia with somatosensory and motor
      cortices. Within the ASD group, significant correlations were found between
      functional connectivity patterns and total RBS-R scores as well as one principal
      component analysis-derived score from the RBS-R. These results suggest that
      thalamocortical resting-state connectivity is altered in individuals with ASD,
      and that resting-state functional connectivity is associated with ASD
      symptomatology.

PMID- 29453962
TI  - An Autoantibody Against Human DNA-Topoisomerase I Is a Novel Biomarker for Non
      Small Cell Lung Cancer.
AB  - BACKGROUND: We previously reported a novel tumor-associated antigen with a
      molecular weight of approximately 48 kDa that was a fragment derived from human
      DNA-topoisomerase I. The aim of this study is to further investigate the clinical
      significance of the autoantibody in patients with non-small cell lung cancer
      (NSCLC). METHODS: We determined serum levels of the autoantibody in 127 NSCLC
      patients, 127 age-, sex-, and smoking history-matched healthy control subjects,
      and 38 patients with pulmonary benign tumors by using a specific enzyme linked
      immunosorbent assay for the autoantibody. We then statistically evaluated its
      clinical application value. RESULTS: Serum levels of the autoantibody in NSCLC
      patients were significantly higher than in healthy control subjects and patients
      with benign tumors (p = 0.001). The percentage of sera with a positive level of
      the autoantibody was 71.8%, 65.6%, 41.9%, and 48.0% in stages I, II, III, and IV
      of the cancer, respectively (p = 0.049). The area under the receiver-operating
      characteristics curve was 0.971 (95% confidence interval: 0.953 to 0988) for
      healthy controls and patients with benign tumors versus early stage NSCLC
      patients. Moreover, the overall survival rate of the patients in stages I, II,
      and IV with negative levels of the autoantibody was significantly lower than that
      of patients with positive levels of the autoantibody (p = 0.013, 0.023, and 0.047
      for stages I, II, and IV, respectively). CONCLUSIONS: Our results indicate that
      the autoantibody can be used as a novel biomarker for the early diagnosis and
      prognosis of NSCLC.

PMID- 29453963
TI  - Significance of Spread Through Air Spaces in Resected Pathological Stage I Lung
      Adenocarcinoma.
AB  - BACKGROUND: "Spread through air spaces" (STAS) is a recently described invasive
      pattern of lung cancer that spreads within air spaces beyond the edge of the main
      tumor. In the current study, we investigated the significance of STAS in patients
      with pathologic stage I adenocarcinoma. METHODS: We assessed STAS in a total of
      276 patients with resected pathologic stage I adenocarcinoma. STAS was classified
      as either no STAS, low STAS (1-4 single cells or clusters of STAS), or high STAS
      (>=5 single cells or clusters of STAS) using a 20x objective and a 10x ocular
      lens. We evaluated the association between STAS and the clinicopathologic
      characteristics and postoperative survivals. RESULTS: Among 276 patients, 123
      (44.6%), 48 (17.4%), and 105 (38.0%) were classified as having no, low, and high
      STAS, respectively. The positivity for STAS was significantly associated with
      larger radiologic tumor diameter (p = 0.008), higher consolidation/tumor ratio (p
      < 0.001), higher maximum standard uptake value (p < 0.001), pathologically larger
      tumor size (p = 0.004), pleural invasion (p = 0.027), and histologically invasive
      type (p < 0.001); whereas STAS was not significantly associated with epidermal
      growth factor receptor mutations or programmed death ligand-1 expression (p =
      0.129 and p = 0.872, respectively). Patients with STAS had significantly shorter
      recurrence-free and overall survival than patients without STAS (p < 0.001 and p
      = 0.002, respectively). According to a multivariate analysis, positivity for STAS
      remained an independent prognostic factor for both recurrence-free survival and
      overall survival. CONCLUSIONS: Spread through air spaces was associated with
      clinicopathologically invasive features and was predictive of worse survival.

PMID- 29453961
TI  - Repeat-associated non-AUG (RAN) translation and other molecular mechanisms in
      Fragile X Tremor Ataxia Syndrome.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset inherited
      neurodegenerative disorder characterized by progressive intention tremor, gait
      ataxia and dementia associated with mild brain atrophy. The cause of FXTAS is a
      premutation expansion, of 55 to 200 CGG repeats localized within the 5'UTR of
      FMR1. These repeats are transcribed in the sense and antisense directions into
      mutants RNAs, which have increased expression in FXTAS. Furthermore, CGG sense
      and CCG antisense expanded repeats are translated into novel proteins despite
      their localization in putatively non-coding regions of the transcript. Here we
      focus on two proposed disease mechanisms for FXTAS: 1) RNA gain-of-function,
      whereby the mutant RNAs bind specific proteins and preclude their normal
      functions, and 2) repeat-associated non-AUG (RAN) translation, whereby
      translation through the CGG or CCG repeats leads to the production of toxic
      homopolypeptides, which in turn interfere with a variety of cellular functions.
      Here, we analyze the data generated to date on both of these potential molecular
      mechanisms and lay out a path forward for determining which factors drive FXTAS
      pathogenicity.

PMID- 29453960
TI  - Synaptic dysfunction and altered excitability in C9ORF72 ALS/FTD.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by a progressive
      degeneration of upper and lower motor neurons, resulting in fatal paralysis due
      to denervation of the muscle. Due to genetic, pathological and symptomatic
      overlap, ALS is now considered a spectrum disease together with frontotemporal
      dementia (FTD), the second most common cause of dementia in individuals under the
      age of 65. Interestingly, in both diseases, there is a large prevalence of RNA
      binding proteins (RBPs) that are mutated and considered disease-causing, or whose
      dysfunction contribute to disease pathogenesis. The most common shared genetic
      mutation in ALS/FTD is a hexanucleuotide repeat expansion within intron 1 of
      C9ORF72 (C9). Three potentially overlapping, putative toxic mechanisms have been
      proposed: loss of function due to haploinsufficient expression of the C9ORF72
      mRNA, gain of function of the repeat RNA aggregates, or RNA foci, and repeat
      associated non-ATG-initiated translation (RAN) of the repeat RNA into toxic
      dipeptide repeats (DPRs). Regardless of the causative mechanism, disease symptoms
      are ultimately caused by a failure of neurotransmission in three regions: the
      brain, the spinal cord, and the neuromuscular junction. Here, we review C9
      ALS/FTD-associated synaptic dysfunction and aberrant neuronal excitability in
      these three key regions, focusing on changes in morphology and synapse formation,
      excitability, and excitotoxicity in patients, animal models, and in vitro models.
      We compare these deficits to those seen in other forms of ALS and FTD in search
      of shared pathways, and discuss the potential targeting of synaptic dysfunctions
      for therapeutic intervention in ALS and FTD patients.

PMID- 29453964
TI  - Conidiogenesis-related DNA photolyase gene in Beauveria bassiana.
AB  - Beauveria bassiana is an entomopathogenic fungi used in environmentally mindful
      pest management. Its main active ingredient, conidia, is commercially available
      as a fungal biopesticide. Many studies of conidia production have focused on how
      to optimize culture conditions for maximum productivity and stability against
      unfavorable abiotic factors. However, understanding of how conidiogenesis-related
      genes provide improved conidial production remains unclear. In this study, we
      focus on identifying conidiogenesis-related genes in B. bassiana ERL1170 using a
      random mutagenesis technique. Transformation of ERL1170 using restriction enzyme
      mediated integration generated one morphologically different transformant,
      ERL1170-pABeG #163. The transformant was confirmed to represent B. bassiana, and
      the binary vector was successfully integrated into the genome of ERL1170.
      Compared to the wild type, transformant #163 showed very slow hyphal growth and
      within 6 days only produced <1 * 106 conidia/0.28 cm2 agar block (wild type: 6.2
      * 107 conidia/agar block). Transformant #163 also exhibited different morphology
      than the wild type, including thicker hyphae with some club-shaped parts. In
      contrast, the typical morphology of wild type B. bassiana exhibits thread-like
      hyphae and conidiophore structures and circular conidia. To determine the
      location of the randomly inserted DNA, we conducted thermal asymmetric interlaced
      (TAIL) PCR and Escherichia coli cloning to clearly sequence the disrupted region.
      We identified one colony (colony No. 7) with an insertion site identified as DNA
      photolyase. This was confirmed through a gene knock-out study. It is possible the
      gene that encodes for DNA photolyase was disrupted during the insertion process
      and might be involved in fungal conidiogenesis. This work serves as a platform
      for exploring the function of a variety of B. bassiana genes involved in pest
      management and their downstream processing.

PMID- 29453965
TI  - Effects of Beauveria bassiana on predation and behavior of the predatory mite
      Phytoseiulus persimilis.
AB  - Determination of intraguild interactions between entomopathogens and predators is
      important when attempting to use a combination of these two natural enemy groups
      for biological control of their shared arthropod pest species. This study
      assessed the effects of Beauveria bassiana on the predation and associated
      behavior of the predatory mite, Phytoseiulus persimilis, against Tetranychus
      urticae. The functional response tests showed that P. persimilis exhibited a
      Holling type II response on the spider mite, Tetranychus urticae, when treated
      with either a B. bassiana or Tween-80 suspension. There were no significant
      differences between the treatments in the number of T. urticae consumed. The
      laboratory choice test indicated that P. persimilis displayed a significant
      avoidance response to B. bassiana on bean leaves immediately following spray
      application. They also spent significantly longer time in self-grooming behavior
      on leaf disks sprayed with fungal conidia than on discs treated with Tween-80.
      There were no significant differences in the predation rates on T. urticae eggs
      between the different treatments. The potted plant investigations indicated that
      P. persimilis showed significant aversion behavior to the initial fungal spray,
      but gradually dispersed over the entire bean plants. Observations using scanning
      electron microscopy revealed that fungal conidia were attached to the body of P.
      persimilis after mounting the leaf disk treated with B. bassiana, which would
      account for its varied behavioral responses. Our study suggests that fungal spray
      did not affect the predation capability of P. persimilis and poses a negligible
      risk to their behavior.

PMID- 29453966
TI  - Gamma irradiation inactivates honey bee fungal, microsporidian, and viral
      pathogens and parasites.
AB  - Managed honey bee (Apis mellifera) populations are currently facing unsustainable
      losses due to a variety of factors. Colonies are challenged with brood pathogens,
      such as the fungal agent of chalkbrood disease, the microsporidian gut parasite
      Nosema spp., and several viruses. These pathogens may be transmitted horizontally
      from worker to worker, vertically from queen to egg and via vectors like the
      parasitic mite, Varroa destructor. Despite the fact that these pathogens are
      widespread and often harbored in wax comb that is reused from year to year and
      transferred across beekeeping operations, few, if any, universal treatments exist
      for their control. In order to mitigate some of these biological threats to honey
      bees and to allow for more sustainable reuse of equipment, investigations into
      techniques for the sterilization of hive equipment and comb are of particular
      significance. Here, we investigated the potential of gamma irradiation for
      inactivation of the fungal pathogen Ascosphaera apis, the microsporidian Nosema
      ceranae and three honey bee viruses (Deformed wing virus [DWV], Black queen cell
      virus [BQCV], and Chronic bee paralysis virus [CBPV]), focusing on the
      infectivity of these pathogens post-irradiation. Results indicate that gamma
      irradiation can effectively inactivate A. apis, N. ceranae, and DWV. Partial
      inactivation was noted for BQCV and CBPV, but this did not reduce effects on
      mortality at the tested, relatively high doses. These findings highlight the
      importance of studying infection rate and symptom development post-treatment and
      not simply rate or quantity detected. These findings suggest that gamma
      irradiation may function as a broad treatment to help mitigate colony losses and
      the spread of pathogens through the exchange of comb across colonies, but raises
      the question why some viruses appear to be unaffected. These results provide the
      basis for subsequent studies on benefits of irradiation of used comb for colony
      health and productivity.

PMID- 29453967
TI  - Discovery of anti-viral molecules and their vital functions in Bombyx mori.
AB  - The silkworm Bombyx mori (B. mori), a lepidopteran model organism, has become an
      important model for molecular biology researches with its genome completely
      sequenced. Silkworms confront different types of virus diseases, mainly including
      those caused by Bombyx mori nucleopolyhedrovirus (BmNPV), Bombyx mori densovirus
      type 1 (BmDNV-1), Bombyx mori bidesovirus (BmBDV) which was termed as Bombyx mori
      densovirus type 2 (BmDNV-2) or Bombyx mori parvo-like virus (BmPLV) before in
      sericulture. B. mori offers excellent models to study the molecular mechanisms of
      insect innate immune responses to viruses. A variety of molecules and pathways
      have been identified to be involved in the immune responses in the silkworm to
      viruses, such as the antimicrobial peptides, prophenoloxidase-activating system,
      apoptosis, ROS, small RNA and related molecules. Here in this review, we
      summarize the current research advances in molecules involved in silkworm anti
      virus pathways. Moreover, taking BmNPV as an example, we proposed a schematic
      model of molecules and pathways involved in silkworm immune responses against
      virus infection. We hope this review can facilitate further study of antiviral
      mechanisms in silkworm, and provide a reference for virus diseases in other
      organisms.

PMID- 29453968
TI  - Lipoprotein lipase: Biosynthesis, regulatory factors, and its role in
      atherosclerosis and other diseases.
AB  - Lipoprotein lipase (LPL) is a rate-limiting enzyme that catalyzes hydrolysis of
      the triglyceride (TG) core of circulating TG-rich lipoproteins including
      chylomicrons (CM), low-density lipoproteins (LDL) and very low-density
      lipoproteins (VLDL). A variety of parenchymal cells can synthesize and secrete
      LPL. Recent studies have demonstrated that complicated processes are involved in
      LPL biosynthesis, secretion and transport. The enzyme activity of LPL is
      regulated by many factors, such as apolipoproteins, angiopoietins, hormones and
      miRNAs. In this article, we also reviewed the roles of LPL in atherosclerosis,
      coronary heart disease, cerebrovascular accident, Alzheimer disease and chronic
      lymphocytic leukemia. LPL in different tissues exerts differential physiological
      functions. The role of LPL in atherosclerosis is still controversial as reported
      in the literature. Here, we focused on the properties of LPL derived from
      macrophages, endothelial cells and smooth muscle cells in the vascular wall. We
      also explore the existence of crosstalk between LPL and those cells when the
      molecule mainly plays a proatherogenic role. This review will provide insightful
      knowledge of LPL and open new therapeutic perspectives.

PMID- 29453969
TI  - S100 proteins in oral squamous cell carcinoma.
AB  - BACKGROUND: Controversy exists in the literature regarding the differential
      expression of S100 protein members and their functional correlations in oral
      squamous cell carcinoma (OSCC). The aim of the present study was to
      systematically review the expression of S100 protein family members among OSCC
      and healthy controls and to evaluate whether S100 protein members serve as
      diagnostic marker in OSCC. METHODS: Indexed databases were searched up to and
      including October 2017. Case-control/cross-sectional studies in human diagnosed
      clinically and/or histologically with OSCC and evaluated the expression of S100
      protein family among OSCC and healthy controls were included. RESULTS: A total of
      11 studies were included. Four studies were of good quality, 5 were of moderate
      and 2 were of poor quality. Five studies evaluated S100A2, A7 and A12 and showed
      overexpression of these protein levels in OSCC patients when compared to healthy
      controls. Three studies reported down-regulation of S100A1, A3, A6, A11, A13,
      A14, A16 and S100Z in OSCC patients as compared to healthy controls. Two studies
      reported overexpression of S100A9 and one study each reported overexpression of
      S100A4, A8, A10, and S100P in OSCCs as compared to healthy controls respectively.
      CONCLUSION: It remains debatable whether up-regulation or down-regulation of
      specific S100 protein members serves as a diagnostic marker in OSCC. With the
      findings of the present systematic review, the threshold for diagnostic levels of
      S100 proteins cannot be proposed. In addition, S100A7 protein could act as a
      potential OSCC marker. However, further case-control studies with larger sample
      size are required to obtain strong conclusion in this regard.

PMID- 29453970
TI  - Proton NMR based serum metabolic profile correlates with the neurological
      recovery in treated acute spinal cord injury (ASCI) subjects: A pilot study.
AB  - BACKGROUND: Acute Spinal Cord Injury (ASCI) is still having substantial morbidity
      and mortality despite of advanced therapeutics. Major obstacles are paucity of
      monitoring tools or biomarkers for severity determination, recovery and
      prognostication. A prospective case control pilot study with serum 1H NMR
      spectroscopic metabolic profiling was carried out to evaluate metabolites
      perturbations and its relationship with recovery and to see role of stem cells in
      facilitating neurological recovery. METHODOLOGY: Twenty subjects with ASCI were
      classified on the basis of therapeutic modality into surgical fixation alone
      (Group-1, n = 10), stem cell adjuvant (Group-2, n = 10) and healthy controls
      (Group-0, n = 10). Serum samples were collected at admission (baseline) and after
      six months (follow-up). NMR data of serum sample were quantified and subjected to
      Wilcoxon and ANOVA tests. Further validation was performed using supervised OSC
      PCA and OPLS-DA by incorporating substantial control samples. RESULT: Twenty
      eight metabolites were identified; well resolved resonances of fifteen
      metabolites were quantified wherein seven were statistically significant.
      Predominantly amino acids and ketone bodies played vital role in the
      differentiation of groups. CONCLUSIONS: Serum NMR spectroscopy reveals certain
      metabolites perturbations having clear correlation with pattern of recovery in
      treated ASCI subject. Stem cells treatment group had comparatively effective
      recovery.

PMID- 29453971
TI  - Prediction value of serum HBV large surface protein in different phases of HBV
      infection and virological response of chronic hepatitis B patients.
AB  - BACKGROUND: Serum HBV large surface protein (HBV-LP) is an envelope protein that
      has a close relationship with HBV DNA level. This study is to explore the
      prediction value of HBV-LP in different phase of HBV infection and during
      antiviral therapy in chronic hepatitis B (CHB) patients. METHODS: A retrospective
      study was conducted in 2033 individuals, which included 1677 HBV infected
      patients in different phases and 356 healthy controls. HBV-LP, HBV serum markers
      and HBV DNA were detected by ELISA, CMIA and qRT-PCR, respectively. 85 CHB
      patients receiving PegIFNalpha or ETV were divided into virological response (VR)
      and partial virological response (PVR). The dynamic changes of HBV DNA and HBV-LP
      were observed. RESULTS: The level of HBV-LP in 2033 individuals was shown as:
      HBeAg-positive hepatitis > HBeAg-positive infection > HBeAg-negative hepatitis >
      HBeAg-negative infection > healthy controls. HBV-LP was positive in all patients
      whose HBV DNA > 1.0E + 06 IU/ml. When HBsAg was <0.05 IU/ml or >1000 IU/ml, HBV
      DNAs were all negative if HBV-LP < 1.0 S/CO. When HBsAg was between 0.05 IU/ml
      and 1000 IU/ml, the consistency of HBV-LP with HBV DNA was 100% in case of HBV-LP
      > 4.0 S/CO in HBeAg-positive patients and HBV-LP > 2.0 S/CO in HBeAg-negative
      ones. During antiviral therapy, baseline HBV-LP was lower in VR patients than
      that in PVR patients. The optimal cut-off points to predict VR by baseline HBV-LP
      were 32.4 and 28.6 S/CO for HBeAg-positive and HBeAg-negative hepatitis patients,
      respectively. CONCLUSIONS: HBV-LP may be a useful marker for distinguishing the
      different phases of HBV infection. Moreover, baseline HBV-LP level can be used
      for predicting VR of CHB patients.

PMID- 29453972
TI  - Artemin regulates CXCR4 expression to induce migration and invasion in pancreatic
      cancer cells through activation of NF-kappaB signaling.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the most lethal human malignant tumor
      because of the early onset of local invasion and distant metastasis. Perineural
      invasion is a prominent characteristic of pancreatic adenocarcinoma, which is a
      multifactorial process that involves various signaling molecules from different
      signaling pathways. The glial cell line-derived neurotrophic factor family of
      ligands was reported to be involved in perineural invasion in pancreatic cancer.
      Artemin is one member of the glial cell line-derived neurotrophic factor family
      of ligands. Although Artemin has previously been demonstrated to promote
      invasiveness of pancreatic cancer, the mechanisms remain poorly understood. In
      this study, we performed an analysis to determine the effects of Artemin on
      modulating tumor cell metastatic potential and invasion activity and explored its
      mechanisms in pancreatic cancer. We indicated that Artemin and CXCR4 were
      overexpressed in cancer tissues and widely expressed in pancreatic cancer cell
      lines. We observed that activation of ERK1/2 and Akt in Artemin-treated cells led
      to enhanced nuclear accumulation of NF-kappaB, which then induced CXCR4
      expression. Through regulation of the expression of CXCR4, Artemin functionally
      promoted the migration and invasion in pancreatic cancer cells. The present study
      indicated that Artemin induced CXCR4 expression by activating Akt and ERK 1/2/NF
      kappaB signaling, thereby modulating tumor cell metastatic potential and invasion
      activity in pancreatic cancer by regulating SDF-1alpha/CXCR4 axis. Artemin might
      be an effective and potent therapeutic target for pancreatic cancer metastasis,
      especially in perineural invasion.

PMID- 29453973
TI  - PAX5 haploinsufficiency induce cancer cell dormancy in Raji cells.
AB  - PAX5 mutations have important role in leukemogenesis and leukemia relapse, cancer
      cell dormancy participates in cancer relapse, but there was no report about PAX5
      mutation inducing cancer cell dormancy. we constructed the PAX5 deletion Raji
      cell lines using gene editing technology, evaluated dormancy biological
      characteristics of cell lines. Our results showed PAX5 haploinsufficiency
      restrained the proliferation of Raji cells, induced G0/G1 arrest of Raji cells,
      reduced chemotherapy sensitivity. The tumor formation rate reduced in PAX5
      mutation Raji cells. Our results showed PAX5 insufficiency induced cancer cell
      dormancy in Raji cell.

PMID- 29453974
TI  - Genetically-modified bone mesenchymal stem cells with TGF-beta3 improve wound
      healing and reduce scar tissue formation in a rabbit model.
AB  - Extensive scar tissue formation often occurs after severe burn injury, trauma, or
      as one of complications after surgical intervention. Despite significant
      therapeutic advances, it is still a significant challenge to manage massive scar
      tissue formation while also promoting normal wound healing. The goal of this
      study was to investigate the therapeutic effect of bone mesenchymal stem cells
      (BMSCs) that were genetically modified to overexpress transforming growth factor
      beta 3 (TGF-beta3), an inhibitor of myofibroblast proliferation and collagen type
      I deposition, on full-thickness cutaneous wound healing in a rabbit model. Twenty
      four rabbits with surgically-induced full-thickness cutaneous wounds created on
      the external ear (1.5 * 1.5 cm, two wounds/ear) were randomized into four groups:
      (G1), wounds with no special treatment but common serum-free culture medium as
      negative controls; (G2), topically-applied recombinant adenovirus, expressing TGF
      beta3/GFP; (G3), topically-applied BMSCs alone; (G4), topically-applied BMSCs
      transfected with Ad-TGF-beta3/GFP (BMSCsTGF-beta3); and (G5), an additional
      normal control (n = 2) with neither wound nor treatment on the external ear skin.
      The sizes of wounds on the ear tissues were grossly examined, and the scar depth
      and density of wounds were histologically evaluated 21, 45, and 90 days after
      surgical wound creation. Our results demonstrated that G4 significantly reduced
      the wound scar depth and density, compared to G1~3. Numbers of cells expressing
      GFP significantly increased in G4, compared to G2. The protein expression of TGF
      beta3 and type III collagen in G4 significantly increased, while the ratio of
      type I to type III collagen was also significantly reduced, which is similar to
      the tissue architecture found in G5, as compared the other treatment groups. In
      conclusion, transplantation of BMSCsTGF-beta3 remarkably improves wound healing
      and reduces skin scar tissue formation in an animal model, which may potentially
      provide an alternative in the treatment of extensive scar tissue formation after
      soft tissue injury.

PMID- 29453975
TI  - miR144-3p inhibits PMVECs excessive proliferation in angiogenesis of
      hepatopulmonary syndrome via Tie2.
AB  - BACKGROUND/AIM: Increasing evidence show microRNAs (miRNAs) are associated with
      hepatopulmonary syndrome (HPS). The aim of this study was to investigate the role
      of miR-144 in the angiogenesis of HPS, as well as to identify its underlying
      mechanism. METHODS: The expression levels of miR-144-3p were assessed in
      pulmonary micro-vascular endothelial cells (PMVECs), as well as in lung tissues
      from rats with HPS. We predicted the potential target of miR-144-3p. Tyrosine
      kinase 2(Tie2) was identified as a target gene of miR144-3p, which has an
      essential role in the angiogenesis of lung vessel. In addition, the effects of
      miR-144-3p regulated on Tie2 was examined. The upregulation and down-regulation
      of miR-144-3p can affect the proliferation of PMVECs. RESULTS: We found that the
      levels of miR-144-3p were frequently downregulated in HPS tissues and cell lines,
      and overexpression of miR-144-3p dramatically inhibited PMVECs proliferation and
      cell cycle. We further verified the Tie2 as a novel and direct target of miR-144
      3p in HPS. CONCLUSION: miR-144-3p can negatively regulate PMVECs proliferation by
      Tie2 expression. In addition, overexpression of miR-144-3p may prove beneficial
      as a therapeutic strategy for HPS treatment.

PMID- 29453977
TI  - Amelioration of progressive autoimmune encephalomyelitis by epigenetic regulation
      involves selective repression of mature neutrophils during the preclinical phase.
AB  - We have recently demonstrated that treatment of NOD mice with the epigenetic drug
      Trichostatin A (TSA) ameliorated myelin peptide induced progressive experimental
      autoimmune encephalomyelitis (P-EAE). Protection was accompanied by induction of
      antigen-specific T-cell tolerance in the periphery and reduced influx of T cells
      into the spinal cord. In this investigation, we examined whether the epigenetic
      drug could impact the innate immune system as well. Whereas the mature (MHC class
      II+) CD11b+Ly-6G+ neutrophils expanded substantially in the peripheral lymphoid
      compartment during the preclinical phase, the MHC class II+, CD11b+Ly-6C+ mature
      monocytes increased modestly throughout the disease course. Amelioration of the
      clinical disease by TSA treatment was accompanied by diminished abundance of
      CD11b+Ly-6Gdim activated neutrophils in secondary lymphoid organs and their
      influx into the spinal cord without affecting monocytes. Interestingly, the co
      inhibitory ligand CD274+ (PD-L1+) but not CD275+ (ICOS-L+), CD39+ or CD11c+
      dendritic cells were decreased in the peripheral lymphoid compartment of drug
      treated mice. Thus, in addition to myelin-specific T cell tolerance induction
      observed previously, selective repression of mature neutrophils and PD-L1+ cells
      is critically involved in the epigenetic regulation of P-EAE.

PMID- 29453976
TI  - Cell-type specific expression of constitutively-active Rheb promotes regeneration
      of bulbospinal respiratory axons following cervical SCI.
AB  - Damage to respiratory neural circuitry and consequent loss of diaphragm function
      is a major cause of morbidity and mortality in individuals suffering from
      traumatic cervical spinal cord injury (SCI). Repair of CNS axons after SCI
      remains a therapeutic challenge, despite current efforts. SCI disrupts
      inspiratory signals originating in the rostral ventral respiratory group (rVRG)
      of the medulla from their phrenic motor neuron (PhMN) targets, resulting in loss
      of diaphragm function. Using a rat model of cervical hemisection SCI, we aimed to
      restore rVRG-PhMN-diaphragm circuitry by stimulating regeneration of injured rVRG
      axons via targeted induction of Rheb (ras homolog enriched in brain), a signaling
      molecule that regulates neuronal-intrinsic axon growth potential. Following C2
      hemisection, we performed intra-rVRG injection of an adeno-associated virus
      serotype-2 (AAV2) vector that drives expression of a constitutively-active form
      of Rheb (cRheb). rVRG neuron-specific cRheb expression robustly increased mTOR
      pathway activity within the transduced rVRG neuron population ipsilateral to the
      hemisection, as assessed by levels of phosphorylated ribosomal S6 kinase. By co
      injecting our novel AAV2-mCherry/WGA anterograde/trans-synaptic axonal tracer
      into rVRG, we found that cRheb expression promoted regeneration of injured rVRG
      axons into the lesion site, while we observed no rVRG axon regrowth with AAV2-GFP
      control. AAV2-cRheb also significantly reduced rVRG axonal dieback within the
      intact spinal cord rostral to the lesion. However, cRheb expression did not
      promote any recovery of ipsilateral hemi-diaphragm function, as assessed by
      inspiratory electromyography (EMG) burst amplitudes. This lack of functional
      recovery was likely because regrowing rVRG fibers did not extend back into the
      caudal spinal cord to synaptically reinnervate PhMNs that we retrogradely-labeled
      with cholera toxin B from the ipsilateral hemi-diaphragm. Our findings
      demonstrate that enhancing neuronal-intrinsic axon growth capacity can promote
      regeneration of injured bulbospinal respiratory axons after SCI, but this
      strategy may need to be combined with other manipulations to achieve reconnection
      of damaged neural circuitry and ultimately recovery of diaphragm function.

PMID- 29453978
TI  - Venlafaxine prevents morphine antinociceptive tolerance: The role of
      neuroinflammation and the l-arginine-nitric oxide pathway.
AB  - Opioid-induced neuroinflammation and the nitric oxide (NO) signal-transduction
      pathway are involved in the development of opioid analgesic tolerance. The
      antidepressant venlafaxine (VLF) modulates NO in nervous tissues, and so we
      investigated its effect on induced tolerance to morphine, neuroinflammation, and
      oxidative stress in mice. Tolerance to the analgesic effects of morphine were
      induced by injecting mice with morphine (50 mg/kg) once a day for three
      consecutive days; the effect of co-administration of VLF (5 or 40 mg/kg) with
      morphine was similarly tested in a separate group. To determine if the NO
      precursor l-arginine hydrochloride (l-arg) or NO are involved in the effects
      rendered by VLF, animals were pre-treated with l-arg (200 mg/kg), or the NO
      synthesis inhibitors N(omega)-nitro-l-arginine methyl ester (L-NAME; 30 mg/kg) or
      aminoguanidine hydrochloride (AG; 100 mg/kg), along with VLF (40 mg/kg) for three
      days before receiving morphine for another three days. Nociception was assessed
      with a hot-plate test on the fourth day, and the concentration of tumor necrosis
      factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6),
      interleukin-10, brain-derived neurotrophic factor, NO, and oxidative stress
      factors such as total thiol, malondialdehyde content, and glutathione peroxidase
      (GPx) activity in the brain was also determined. Co-administration of VLF with
      morphine attenuated morphine-induced analgesic tolerance and prevented the
      upregulation of proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), NO,
      and malondialdehyde in brains of mice with induced morphine tolerance; chronic
      VLF administration inhibited this decrease in brain-derived neurotrophic factor,
      total thiol, and GPx levels. Moreover, repeated administration of l-arg before
      receipt of VLF antagonized the effects induced by VLF, while L-NAME and AG
      potentiated these effects. VLF attenuates morphine-induced analgesic tolerance,
      at least partly because of its anti-inflammatory and antioxidative properties.
      VLF also appears to suppress the development of morphine-induced analgesic
      tolerance through an l-arg-NO-mediated mechanism.

PMID- 29453979
TI  - Toward a Meaningful Definition of Recovery After Hip Fracture: Comparing Two
      Definitions for Community-Dwelling Older Adults.
AB  - OBJECTIVES: To examine the course of recovery and resulting health-related
      quality of life (HRQL) after low-trauma hip fracture using 2 different
      definitions of recovery. DESIGN: Inception cohort with 8 assessments over 1 year.
      SETTING: Participants were recruited from a tertiary-care hospital and followed
      up in the community. PARTICIPANTS: Community-dwelling hip fracture patients
      (N=47, 75% of all eligible; aged >=65y). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Prefracture functional level was used to identify subgroups of
      participants with similar trajectories of mobility over time. Recovery in
      functional mobility was defined in 2 ways: the "traditional" definition (return
      to prefracture level of functional mobility) and a "targeted recovery" definition
      (ability to climb 10 steps). Both were measured using the Lower Extremity
      Functional Scale. HRQL was measured using the RAND 36-Item Short-Form Health
      Survey. RESULTS: Participants were categorized into 3 subgroups with: low,
      medium, and high prefracture functional abilities. Agreement between the 2
      definitions of recovery (quantified using kappa coefficient) was strong for the
      medium group (.81; 95% confidence interval, .56-1.00), weak for the high group
      (.46; 95% confidence interval, 0.0-.99), and minimal for the low group (.12; 95%
      confidence interval, 0.0-.328). Contrary to the traditional definition, patients
      who achieved targeted recovery had statistically and clinically better HRQL than
      the rest of the cohort throughout the study (estimated average difference of 10.8
      points on RAND 36-Item Short-Form Health Survey; 95% confidence interval, 6.67
      15.07). CONCLUSIONS: The agreement between the 2 definitions of recovery ranged
      from minimal to strong according to patient group. Using a functional target to
      define recovery predicted HRQL better. It is vital to consider the definition of
      recovery carefully for research or clinical practice because it can influence
      subsequent decisions (eg, endorsing a specific intervention or discharging
      patients).

PMID- 29453980
TI  - Virtual Reality for Upper Limb Rehabilitation in Subacute and Chronic Stroke: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: To evaluate the effectiveness of reinforced feedback in virtual
      environment (RFVE) treatment combined with conventional rehabilitation (CR) in
      comparison with CR alone, and to study whether changes are related to stroke
      etiology (ie, ischemic, hemorrhagic). DESIGN: Randomized controlled trial.
      SETTING: Hospital facility for intensive rehabilitation. PARTICIPANTS: Patients
      (N=136) within 1 year from onset of a single stroke (ischemic: n=78, hemorrhagic:
      n=58). INTERVENTIONS: The experimental treatment was based on the combination of
      RFVE with CR, whereas control treatment was based on the same amount of CR. Both
      treatments lasted 2 hours daily, 5d/wk, for 4 weeks. MAIN OUTCOME MEASURES: Fugl
      Meyer upper extremity scale (F-M UE) (primary outcome), FIM, National Institutes
      of Health Stroke Scale (NIHSS), and Edmonton Symptom Assessment Scale (ESAS)
      (secondary outcomes). Kinematic parameters of requested movements included
      duration (time), mean linear velocity (speed), and number of submovements (peak)
      (secondary outcomes). RESULTS: Patients were randomized in 2 groups (RFVE with
      CR: n=68, CR: n=68) and stratified by stroke etiology (ischemic or hemorrhagic).
      Both groups improved after treatment, but the experimental group had better
      results than the control group (Mann-Whitney U test) for F-M UE (P<.001), FIM
      (P<.001), NIHSS (P<=.014), ESAS (P<=.022), time (P<.001), speed (P<.001), and
      peak (P<.001). Stroke etiology did not have significant effects on patient
      outcomes. CONCLUSIONS: The RFVE therapy combined with CR treatment promotes
      better outcomes for upper limb than the same amount of CR, regardless of stroke
      etiology.

PMID- 29453981
TI  - The C2'- and C3'-endo equilibrium for AMP molecules bound in the cystathionine
      beta-synthase domain.
AB  - The equilibrium between C2'- and C3'-endo conformations of nucleotides in
      solution, as well as their polymers DNA and RNA, has been well studied in
      previous work. However, this equilibrium of nucleotides in their binding state
      remains unclear. We observed two AMP molecules, in C3'- and C2'-endo
      conformations respectively, simultaneously bound to a cystathionine-beta-synthase
      (CBS) domain dimer of the magnesium and cobalt efflux protein CorC in the
      crystallographic study. The C2'-endo AMP molecule assumes the higher sugar pucker
      energy and one more hydrogen bond with the protein than the C3'-endo molecule
      does. The balance between the high sugar pucker energy and the low binding energy
      suggests an equilibrium or switch between C2'- and C3'-endo conformations of the
      bound nucleotides. Our work challenge the previous hypothesis that the ribose of
      the bound nucleotides would be locked in a fixed conformation.

PMID- 29453982
TI  - Glucagon-like peptide-1 contributes to increases ABCA1 expression by
      downregulating miR-758 to regulate cholesterol homeostasis.
AB  - Abnormal regulation of lipid metabolism is associated with type 2 diabetes
      mellitus (T2DM). GLP-1 as a new treatment for T2DM, has unique effects in
      modulating cholesterol homeostasis. However, the mechanism of this effect is
      largely missing. The aim of this study was to determine the effects of GLP-1 on
      cholesterol-induced lipotoxicity in hepatocytes and examine the underlying
      mechanisms. The cell viability was determined, and caspase-3 was used to detect
      the effects of GLP-1 on cholesterol-induced apoptosis. The alterations of miR-758
      and ATP-binding cassette transporter A1 (ABCA1) resulting from cholesterol
      incubation or GLP-1 were detected by qRT-PCR and Western blot assays.
      Overexpression of miR-758 abrogated the GLP-1-mediated ABCA1 expression, and
      conversely, down-regulation of miR-758 aggravated GLP-1's action and revealed
      significant promotion effects. BODIPY-Cholesterol efflux assay revealed that
      treatment with miR-758 inhibitor significantly enhanced ABCA1-dependent
      cholesterol efflux, resulting in reduced total cholesterol. Furthermore, Oil red
      O staining and cholesterol measurement were used to detect lipid accumulation. As
      a result, cholesterol significantly attenuated cell viability, promoted cell
      apoptosis, and facilitated lipid accumulation, and these effects were reversed by
      GLP-1. This study provides evidence that, in HepG2 cells, GLP-1 may affect
      cholesterol homeostasis by regulating the expression of miR-758 and ABCA1. These
      data can inform the development of biomarkers for miR-758, and potentially other
      drugs, on the key pathways of lipid metabolism.

PMID- 29453983
TI  - Aldolase A overexpression is associated with poor prognosis and promotes tumor
      progression by the epithelial-mesenchymal transition in colon cancer.
AB  - There is increasing evidence that glycolysis is involved in cancer progression.
      Aldolase is a glycolytic enzyme that catalyzes the reversible conversion of
      fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone
      phosphate. Disruption of the aldolase genes also plays a role in the progression
      of multiple types of cancer. However, the underlying mechanism of the action of
      aldolases in colon cancer progression remains elusive. In this study, aldolase A
      expression was investigated and found to be upregulated along with human colon
      cancer progression and metastasis at both the mRNA and protein levels in human
      colon cancer tissues. In addition, silencing aldolase A suppressed colon cancer
      cell proliferation and invasion and inhibited the EMT phenotype. Aldolase A
      protein expression in colon cancer was related to tumor location, tumor clinical
      stage and survival. Kaplan-Meier analysis showed that high aldolase A protein
      expression was associated with an unfavorable outcome. Moreover, aldolase A
      affected the development of colon cancer not only by affecting the glucose
      metabolism but also by interacting with the HIF-1 and other EMT-related signaling
      pathways; silencing aldolase A resulted in the reduced activity of these
      signaling pathways. These results indicate that aldolase A has additional non
      glycolytic functions in transcriptional EMT regulation and may therefore have
      potential as a therapeutic target or a biomarker for identifying patients at risk
      for poorer survival.

PMID- 29453984
TI  - GATA3 acetylation at K119 by CBP inhibits cell migration and invasion in lung
      adenocarcinoma.
AB  - GATA3 is a transcriptional factor involved in the development of multiple organs.
      Post translational modifications of GATA3 are critical to its function. Here, we
      report that GATA3 interacts with and is acetylated by the acetyltransferase CBP.
      Class I deacetylases HDAC1, HDAC2 and HDAC3 deacetylate GATA3. The major
      acetylated site of GATA3 in lung adenocarcinoma cells was determined at lysine
      119 (AcK119). Functionally, GATA3-acetylation mimics K119Q mutant was found to
      inhibit lung adenocarcinoma cell migration and invasion with concomitant
      downregulation of EMT-controlling transcriptional factors Slug, Zeb1 and Zeb2.
      Taken together, we demonstrated that GATA3 acetylation at lysine 119 by CBP
      hinders the migration and invasion of lung adenocarcinoma cells.

PMID- 29453985
TI  - Zika virus infected primary microglia impairs NPCs proliferation and
      differentiation.
AB  - Zika virus (ZIKV) can lead to severe birth defects especially microcephaly in
      newborns by infecting human neural progenitors and impairing brain development.
      However, as the resident immune cells in the brain, the role of microglia in the
      ZIKV pathology is not clearly defined. To understand the interplay between immune
      response and neural cells, we investigate the interaction between microglia and
      NPCs during ZIKV infection. Our results demonstrate that primary microglia
      infected with ZIKV induces an inflammatory response similar to that in human,
      producing high level of tumor necrosis factor alpha (TNF-alpha), interleukin 6
      (IL-6), interleukin 1beta (IL-1beta) and inducible nitric oxide synthase (iNOS).
      Furthermore, conditional medium (CM) of ZIKV infected microglia showed inhibitory
      effects on cell proliferation and neuronal differentiation of neural precursor
      cells (NPCs) derived from E14 mice brain. Blocking cytokines in the CM remarkably
      improved neurogenesis and decreased astrocytic differentiation of NPCs. Together,
      our results suggest that microglia mediated neuroinflammation plays an important
      role in neuropathogenesis during ZIKV infection.

PMID- 29453986
TI  - Sterol O-acyltransferase 1 deficiency improves defective insulin signaling in the
      brains of mice fed a high-fat diet.
AB  - Insulin resistance induced by a high-fat diet (HFD) is related to metabolic
      diseases, and sterol O-acyltransferase 1 (SOAT1) is a key enzyme for the
      biosynthesis of cholesteryl ester. In the present study, wild-type (WT) mice and
      SOAT1-knockout (KO) mice with a C57BL6 background fed a HFD were used to explore
      the role of SOAT1 in the hypothalamus. The results show that the WT mice
      exhibited a significant increase in body weight as well as hepatic histologic
      changes; they also had a lower glucose and insulin tolerance than the WT mice fed
      a normal diet. However, the metabolic syndrome was attenuated in the SOAT1-KO HFD
      fed mice. With regard to brain function, the SOAT1-KO HFD-fed mice showed
      improved cognitive function; they also manifested reduced levels of pro
      inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), and IL-6, which would otherwise be raised by a HFD.
      In addition, the HFD led to the overexpression of GFAP and phosphorylated NF
      kappaB in the hypothalamus, changes that were reversed in the SOAT1-KO HFD-fed
      mice. Moreover, SOAT1-KO mice improved HFD-caused defective hypothalamic insulin
      resistance, as evidenced by the upregulation of p-insulin receptor (INSR), p-AKT
      and p-glycogen synthase kinase (GSK)-3beta, while the downregulation of p-AMP
      activated protein kinase (AMPK)-alpha and p-acetyl-CoA carboxylase (ACC)-alpha.
      In addition, similar results were observed in high fructose (HFR)-stimulated
      astrocytes (ASTs) isolated from WT or KO mice. These results suggest that SOAT1
      plays an important role in hypothalamic insulin sensitivity, linked to cognitive
      impairment, in HFD-fed mice.

PMID- 29453987
TI  - The role of Foxq1 in proliferation of human dental pulp stem cell.
AB  - This study aimed to investigate the role for Foxq1 in proliferation activity
      regulation of dental pulp stem cells (DPSCs). Proliferation of DPSC was induced
      by calcium hydroxide, then expression alteration of Foxq1 was evaluated.
      Lentivirus was employed to manipulate Foxq1 level in DPSC, and proliferation
      activities were evaluated. To look into mechanism regulating Foxq1 level after
      calcium hydroxide stimulation, expressions of various microRNAs were evaluated,
      then bioinformatics study and dual-luciferase study were carried out to confirm
      targeting relationship between microRNA and Foxq1. The result of our study
      indicated that proliferation activities of DPSCs were enhanced after calcium
      hydroxide stimulation, during which expression of Foxq1 was also up-regulated.
      Cell viability and progression from G1 to S phase were both improved with
      overexpression of Foxq1, and microRNAs profiling study and dual-luciferase result
      suggested miR-320b contributed to the up-regulation of Foxq1 after calcium
      hydroxide stimulation. These results suggested that miR-320b mediated Foxq1 up
      regulation promote proliferation of dental pulp stem cells.

PMID- 29453988
TI  - Silencing calreticulin gene might protect cardiomyocytes from angiotensin II
      induced apoptosis.
AB  - AIMS: Calreticulin (CRT), as a chaperone, contributes to protein folding and
      quality control cycle. CRT is an important factor regulating Ca2+ that
      participates in cell apoptosis. However, the function of CRT in the heart is
      still controversial. Therefore, we aimed to investigate the potential role of CRT
      in angiotensin II-induced cardiomyocytes apoptosis. MAIN METHODS: Primary
      cultured neonatal cardiomyocytes were stimulated with angiotensin II to induce
      the apoptosis. Expression of CRT and endoplasmic reticulum (ER) stress associated
      protein was detected by western blotting after angiotensin II stimulation for 24
      h. The reactive oxygen species (ROS) production and mitochondrial membrane
      potential (MMP) were also detected. Additionally, the function of CRT on
      cardiomyocytes apoptosis and ER stress/unfolded protein response signaling
      pathway was investigated by transfecting specific CRT-targeting siRNA. KEY
      FINDINGS: Cardiomyocytes apoptosis was induced by angiotensin II. The protein
      level of CRT was elevated after angiotensin -II stimulation for 24 h.
      Additionally, the protein levels of GRP78, ATF4, C-ATF6, CHOP and the ROS
      production were elevated, but the Bcl-2 expression and the level of MMP were down
      regulated. After silencing CRT gene in the process of angiotensin II-induced
      cardiomyocytes apoptosis, cardiomyocytes apoptosis rate decreased, meanwhile the
      protein expression of CRT, GRP78, ATF4, C-ATF6 and CHOP were down-regulated.
      However, the Bcl-2 expression was up-regulated, and the increase of ROS and the
      loss of MMP were alleviated. SIGNIFICANCE: Our study demonstrated that CRT might
      protect cardiomyocytes from apoptosis induced by angiotensin II, in which ER
      stress and mitochondria function were identified as possible underlying molecular
      bases.

PMID- 29453989
TI  - Management of bacterial postoperative endophthalmitis and the role of vitrectomy.
AB  - Management of postoperative bacterial endophthalmitis was explored in the
      Endophthalmitis Vitrectomy Study37 in 1995, which has underpinned the core
      protocols in treatment ever since. While surgical techniques have continued to
      evolve, little has changed in the overall clinical management as no further large
      randomized controlled trials have taken place. We review the literature
      addressing the incidence of endophthalmitis, pathogens, antibiotic therapies, and
      the role of vitrectomy. We suggest an update to management protocols based on
      available evidence. While vitreous culture remains the gold standard for
      diagnosis, new techniques allow bacterial identification after antibiotic
      administration, so injection should be initiated immediately. Current antibiotic
      regimes are comprehensive and do not need changing. Intravitreal antibiotics
      should not be repeated at 48 hours after initial treatment. Vitrectomy should be
      considered instead if the clinical picture is not improving.

PMID- 29453990
TI  - ATP-activated P2X7 receptor in the pathophysiology of mood disorders and as an
      emerging target for the development of novel antidepressant therapeutics.
AB  - Mood disorders are a group of psychiatric conditions that represent leading
      global disease burdens. Increasing evidence from clinical and preclinical studies
      supports that innate immune system dysfunction plays an important part in the
      pathophysiology of mood disorders. P2X7 receptor, belonging to the ligand-gated
      ion channel P2X subfamily of purinergic P2 receptors for extracellular ATP, is
      highly expressed in immune cells including microglia in the central nervous
      system (CNS) and has a vital role in mediating innate immune response. The P2X7
      receptor is also important in neuron-glia signalling in the CNS. The gene
      encoding human P2X7 receptor is located in a locus of susceptibility to mood
      disorders. In this review, we will discuss the recent progress in understanding
      the role of the P2X7 receptor in the pathogenesis and development of mood
      disorders and in discovering CNS-penetrable P2X7 antagonists for potential uses
      in in vivo imaging to monitor brain inflammation and antidepressant therapeutics.

PMID- 29453991
TI  - Identification of branched-chain amino acid aminotransferases active towards (R)
      (+)-1-phenylethylamine among PLP fold type IV transaminases.
AB  - New class IV transaminases with activity towards L-Leu, which is typical of
      branched-chain amino acid aminotransferases (BCAT), and with activity towards (R)
      (+)-1-phenylethylamine ((R)-PEA), which is typical of (R)-selective (R)
      amine:pyruvate transaminases, were identified by bioinformatics analysis,
      obtained in recombinant form, and analyzed. The values of catalytic activities in
      the reaction with L-Leu and (R)-PEA are comparable to those measured for
      characteristic transaminases with the corresponding specificity. Earlier, (R)
      selective class IV transaminases were found to be active, apart from (R)-PEA,
      only with some other (R)-primary amines and D-amino acids. Sequences encoding new
      transaminases with mixed type of activity were found by searching for changes in
      the conserved motifs of sequences of BCAT by different bioinformatics tools.

PMID- 29453992
TI  - Serum cystatin C level is associated with carotid arterial wall elasticity in
      subjects with type 2 diabetes mellitus: A potential marker of early-stage
      atherosclerosis.
AB  - AIMS: Detection of early-stage atherosclerosis in type 2 diabetes mellitus (T2DM)
      patients is important for preventing cardiovascular disease. A phased tracking
      method for evaluating arterial wall elasticity sensitively detects early-stage
      atherosclerosis. However, biochemical markers for early-stage atherosclerosis
      have yet to be established. METHODS: This cross-sectional study enrolled 180 T2DM
      patients, who were classified as not having atherosclerosis according to the
      carotid intima-media thickness (IMT) criteria. We measured serum cystatin C, the
      estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine
      ratio (ACR), and analyzed the associations between these markers and arterial
      wall elasticity (Etheta), IMT and the cardio-ankle velocity index. RESULTS:
      Multiple linear regression analyses revealed that cystatin C was significantly
      associated with Etheta, while neither eGFR nor ACR showed an association.
      Furthermore, among the examined atherosclerotic markers, Etheta was most reliably
      associated with cystatin C. Additionally, the association between cystatin C and
      Etheta disappeared in the low elasticity subgroup, which included subjects in
      whom no atherosclerotic changes had yet been initiated. CONCLUSIONS: In T2DM
      patients without apparent arterial wall thickening, cystatin C is strongly and
      independently associated with arterial wall elasticity, which reflects the degree
      of subclinical atherosclerosis. Thus, cystatin C is a potentially useful marker
      of early-stage atherosclerosis.

PMID- 29453993
TI  - The tegumental allergen-like proteins of Schistosoma mansoni: A biochemical study
      of SmTAL4-TAL13.
AB  - Schistosoma mansoni, like other trematodes, expresses a number of unusual calcium
      binding proteins which consist of an EF-hand domain joined to a dynein light
      chain-like (DLC-like) domain by a flexible linker. These proteins have been
      implicated in host immune responses and drug binding. Three members of this
      protein family from S. mansoni (SmTAL1, SmTAL2 and SmTAL3) have been well
      characterised biochemically. Here we characterise the remaining family members
      from this species (SmTAL4-13). All of these proteins form homodimers and all
      except SmTAL5 bind to calcium and manganese ions. SmTAL9, 10 and 11 also bind to
      magnesium ions. The antischistosomal drug, praziquantel interacts with SmTAL4, 5
      and 8. Some family members also bind to calmodulin antagonists such as
      chlorpromazine and trifluoperazine. Molecular modelling suggests that all ten
      proteins adopt similar overall folds with the EF-hand and DLC-like domains
      folding discretely. Bioinformatics analyses suggest that the proteins may fall
      into two main categories: (i) those which bind calcium ions reversibly at the
      second EF-hand and may play a role in signalling (SmTAL1, 2, 8 and 12) and (ii)
      those which bind calcium ions at the first EF-hand and may play either signalling
      or structural roles (SmTAL7, 9, 10 and 13). The remaining proteins include those
      which do not bind calcium ions (SmTAL3 and 5) and three other proteins (SmTAL4, 6
      and 11). The roles of these proteins are less clear, but they may also have
      structural roles.

PMID- 29453994
TI  - Land use change and conversion effects on ground water quality trends: An
      integration of land change modeler in GIS and a new Ground Water Quality Index
      developed by fuzzy multi-criteria group decision-making models.
AB  - This study aggregated Land Change Modeller (LCM) as a useful model in GIS with an
      extended Groundwater Quality Index (GWQI) developed by fuzzy Multi-Criteria Group
      Decision-Making models to investigate the effect of land use change and
      conversion on groundwater quality being supplied for drinking. The model's
      performance was examined through an applied study in Shiraz, Iran, in a five year
      period (2011 to 2015). Four land use maps including urban, industrial, garden,
      and bare were employed in LCM model and the impact of change in area and their
      conversion to each other on GWQI changes was analysed. The correlation analysis
      indicated that increase in the urban land use area and conversion of bare to the
      residential/industrial land uses, had a relation with water quality decrease.
      Integration of LCM and GWQI can accurately and logically provide a numerical
      analysis of the possible impact of land use change and conversion, as one of the
      influencing factors, on the groundwater quality. Hence, the methodology could be
      used in urban development planning and management in macro level.

PMID- 29453995
TI  - Changes of lipid peroxidation and glutathione redox system, and expression of
      glutathione peroxidase regulatory genes as effect of short-term aflatoxin B1
      exposure in common carp.
AB  - Lipid peroxidation, glutathione content, glutathione peroxidase activity and gene
      expression of transcription factors, glutathione peroxidase, glutathione
      synthetase and glutathione reductase was investigated in common carp liver. Short
      term (24 h) exposure of aflatoxin B1 at different doses (100, 200 and 400 MUg
      AFB1 kg-1 feed) was used. It was found that conjugated dienes and trienes
      elevated after 16 h, while thiobarbituric acid reactive substances content
      increased only at the lowest dose after 16 and 24 h of exposure. Glutathione
      content showed higher levels than control after 16 h of exposure and glutathione
      peroxidase (GPx4) activity was higher in all of the AFB1 treated than the control
      group after 8 h of exposure. Gene expression of transcription factors showed dual
      response. Expression of keap1 gene down-regulated after 8 h and 16 h and nrf2
      gene after16 h, but up-regulated after 24 h of exposure in the lowest, and
      highest dose groups. Expression of gpx4a and gpx4b genes down-regulated after 8 h
      and induction was found after 16 and 24 h of exposure, irrespective of the dose.
      The results indicated that low dose of AFB1 provokes oxidative stress earlier
      than higher doses, which activated the Keap1-Nrf2 pathway. At higher doses this
      pathway activated later, but preformed GPx4 effectively prevented lipid
      peroxidation.

PMID- 29453996
TI  - Systematic review of botulinum toxin treatment for oromandibular dystonia.
AB  - Oromandibular dystonia (OMD) is an isolated focal dystonia that affects the
      muscles of the jaw, lower face and tongue. It is a rare disorder but is
      associated with significant impairment in quality of life. Treatment with oral
      medications has not been successful. Surgical interventions, such as deep brain
      stimulation, may be of benefit but have not been adequately evaluated. Currently,
      botulinum toxin (BoNT) injections are regarded as the treatment of choice for
      OMD. However, the evidence supporting this is not available. Most studies are
      open label, observational studies, longitudinal clinical experience, case reports
      or retrospective analysis. From the available studies, OMD is responsive to
      appropriately targeted BoNT injections. Jaw closing dystonia responds the most
      robustly. Jaw opening dystonia is more complex to inject, but clinical experience
      is consistent with benefit. Lingual dystonia is the most difficult because
      injections into tongue muscles frequently give rise to dysphagia. More controlled
      studies are required to establish BoNT as an effective treatment for OMD.

PMID- 29453997
TI  - Effects of para-methoxyamphetamine (PMA) on agonistic encounters between male
      mice.
AB  - Para-methoxyamphetamine (PMA) is a synthetic drug chemically similar to the
      recreational drug 3,4-methylenedioxy-methamphetamine (MDMA or "ecstasy") and
      often replaces MDMA in tablets that show an "ecstasy" logo. PMA displays a higher
      toxic potential than MDMA, but the behavioral profile of PMA has been scarcely
      studied in animal models. Here we evaluated the effects of PMA (2, 4, 8, and 12
      mg/kg, i.p.) on agonist encounters between male mice using an ethopharmacological
      approach, the isolation-induced aggression model. Likewise, since PMA and MDMA
      share common mechanisms of action, we compared the behavioral profile of PMA with
      that induced by MDMA (8 mg/kg, i.p.) which behavioral effects in this model are
      well characterized. Individually housed mice were exposed to anosmic standard
      opponents 30 min after drug administration. The encounters were videotaped and
      evaluated using an ethologically based analysis. PMA (all doses) significantly
      reduced offensive behaviors (threat and attack), however, a detailed behavioral
      analysis suggests that the observed antiaggressive effect seems to be unspecific,
      showing a complex dose-dependent behavioral profile. Thus, antiaggresive actions
      observed after the administration of the lowest dose were accompanied by
      increases in social investigation, avoidance/flee behaviors and non-social
      explorations, together with a reduction of digging behavior. This pattern
      reflects both approach-contact behaviors and avoidance-flee behaviors. From 4
      mg/kg to 12 mg/kg, the increase in social investigation previously observed
      disappears, and there is a slight increase in immobility, together with a
      different behavioral pattern that suggests anxiogenic effects of PMA, similar to
      those reported after the administration of MDMA. The higher doses of PMA exhibit
      a behavioral profile very similar to that observed in animals treated with MDMA,
      with the exception of the immobility produced by PMA. These findings show for the
      first time the non-specific antiaggressive profile of PMA in the model of
      aggression induced by isolation in male mice.

PMID- 29453998
TI  - CTL14, a recognition receptor induced in late stage larvae, modulates anti-fungal
      immunity in cotton bollworm Helicoverpa armigera.
AB  - C-type lectin (CTL) is usually considered as pattern recognition receptors in
      insect innate immunity. Here we found that CTL14 of Helicoverpa armigera was only
      activated in the fifth instar larvae not in the second instar by entomopathogen
      Beauveria bassiana infection. Recombinant CTL14 protein was found to form
      aggregates with zymosan and B. bassiana in vitro. Immunoprecipitation studies
      demonstrated that CTL14 interacted with serine proteinases (SP), serine
      proteinase inhibitor (serpin), prophenoloxidases (PPO) and vitellogenin (Vg) in
      the larval hemolymph. Furthermore, depletion of CTL14 using dsRNA led to dramatic
      decrease in the expression level of PPO1. Additionally, CTL14 depleted H.
      armigera decreased the resistance to fungal challenge. Taken together, our study
      showed the direct involvement of CTL14 in the anti-fungal immunity of H.
      armigera, which further explained the stronger immune responses in the fifth
      instar compared to the second instar larvae.

PMID- 29453999
TI  - Evolutionary and expression analyses reveal a pattern of ancient duplications and
      functional specializations in the diversification of the Downstream of Kinase
      (DOK) genes.
AB  - Downstream of Kinase (DOK) proteins represent a multigenic family of adaptors
      that includes negative regulators of immune cell signaling. Using phylogenetics
      and intron/exon structure data, we show here that the seven human DOK genes (DOK1
      to DOK7) form three highly divergent groups that emerged before the protostome
      deuterostome split: DOK1/2/3, DOK4/5/6, and DOK7. For two of these three groups
      (DOK1/2/3 and DOK4/5/6), further gene duplications occurred in vertebrates and so
      while chordates only have three DOK genes, vertebrates have seven DOK genes over
      the three groups. From our expression analysis in humans, we show that each group
      of DOK genes has a distinct pattern of expression. The DOK1/2/3 group is immune
      specific, yet each of the three genes in the group has a distinct pattern of
      expression in immune cells. This immune specificity could thus be ancestral, with
      the DOK1/2/3 gene also being immune-related in protostomes. The DOK4/5/6 and DOK7
      groups represent genes that are much less expressed in immune system than the
      DOK1/2/3 group. Interestingly, we identify a novel tyrosine based motif that is
      specific to the vertebrate DOK4/5/6 sequences. The evolution of the DOK genes is
      thus marked by a pattern of ancient duplications and functional specializations.

PMID- 29454001
TI  - Brain bioenergetics in rats with acute hyperphenylalaninemia.
AB  - Phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism caused by
      deficient phenylalanine hydroxylase (PAH) activity. The deficiency results in
      increased levels of Phe and its metabolites in fluids and tissues of patients.
      PKU patients present neurological signs and symptoms including hypomyelination
      and intellectual deficit. This study assessed brain bioenergetics at 1 h after
      acute Phe administration to induce hyperphenylalaninemia (HPA) in rats. Wistar
      rats were randomized in two groups: HPA animals received a single subcutaneous
      administration of Phe (5.2 MUmol/g) plus p-Cl-Phe (PAH inhibitor) (0.9 MUmol/g);
      control animals received a single injection of 0.9% NaCl. In cerebral cortex, HPA
      group showed lower mitochondrial mass, lower glycogen levels, as well as lower
      activities of complexes I-III and IV, ATP synthase and citrate synthase. Higher
      levels of free Pi and phospho-AMPK, and higher activities of LDH, alpha
      ketoglutarate dehydrogenase and isocitrate dehydrogenase were also reported in
      cerebral cortex of HPA animals. In striatum, HPA animals had higher LDH (pyruvate
      to lactate) and isocitrate dehydrogenase activities, and lower activities of
      alpha-ketoglutarate dehydrogenase and complex IV, as well as lower phospho-AMPK
      immunocontent. In hippocampus, HPA rats had higher mRNA expression for MFN1 and
      higher activities of alpha-ketoglutarate dehydrogenase and isocitrate
      dehydrogenase, but decreased activities of pyruvate dehydrogenase and complexes I
      and IV. In conclusion, our data demonstrated impaired bioenergetics in cerebral
      cortex, striatum and hippocampus of HPA rats.

PMID- 29454002
TI  - Biodiversity: The new kid on the block?

PMID- 29454000
TI  - Anticipatory stress associated with functional magnetic resonance imaging:
      Implications for psychosocial stress research.
AB  - Stress tasks performed during functional magnetic resonance imaging (fMRI) elicit
      a relatively small cortisol response compared to stress tasks completed in a
      traditional behavioral laboratory, which may be due to apprehension of fMRI that
      elicits an anticipatory stress response. The present study investigated whether
      anticipatory stress is greater prior to research completed in an MRI environment
      than in a traditional behavioral laboratory. Anticipatory stress (indexed by
      cortisol) was greater prior to testing in the MRI environment than traditional
      behavioral laboratory. Furthermore, anticipation of fMRI elicited a cortisol
      response commensurate with the response to the stress task in the behavioral
      laboratory. However, in the MRI environment, post-stress cortisol was
      significantly lower than baseline cortisol. Taken together, these findings
      suggest the stress elicited by anticipation of fMRI may lead to acute elevations
      in cortisol prior to scanning, which may in turn disrupt the cortisol response to
      stress tasks performed during scanning.

PMID- 29454003
TI  - Long-term clinical effects of early thymectomy: Associations with autoimmune
      diseases, cancer, infections, and atopic diseases.

PMID- 29454005
TI  - A quest to find good primers for gene expression analysis of Candida albicans
      from clinical samples.
AB  - Biofilm production contributes to several human diseases, including oral
      candidiasis. Among the Candida species, Candida albicans is the most prevalent.
      The expression of virulence genes is implicated in the pathogenic potential of
      Candida biofilms. However, the evaluation of microbial gene expression from in
      vivo biofilm samples is not trivial, specifically, assessment via quantitative
      PCR (qPCR) can be a challenge because of several species present in clinical
      samples. Hence, the necessity of primers specificity. The aim of this study was
      to evaluate through in silico and in vitro analyses the specificity of published
      primers and newly designed primers for C. albicans virulence genes: ALS1, CAP1,
      CAT1, EFG1, HWP1, LIP3, PLB1, SAP1, SAP4, SOD1, SOD5 and ACT1 (normalizing gene).
      In silico analysis was performed through a PubMed search of articles with primer
      sequences that evaluated gene expression of C. albicans. Then, the sequence
      similarity of twenty-eight primers was checked through BLASTn and ClustalW2. The
      analysis of secondary structures was performed using mfold. When the primers did
      not present satisfactory characteristics (absence of secondary structures, not
      discrepant Tm of forward and reverse sequences and specificity) following in
      vitro analysis (i.e., end point PCR), new primers were designed using Beacon
      DesignerTM and sequences obtained from the "Candida Genome Database". The
      selected primers were tested in vitro by end point PCR using a panel of genomic
      DNA from five different Candida species (C. albicans, Candida glabrata, Candida
      dubliniensis, Candida krusei, and Candida tropicalis). The resulting PCR products
      were visualized on agarose gel. qPCR reactions were performed to determine
      primers' optimal concentration and PCR efficiency. End point PCR demonstrated
      that published primers for the SAP1 and HWP1 were specific for C. albicans and
      the one for SOD1 reacted with C. albicans and C. dubliniensis. The sequence of
      primers designed for ACT1, ALS1 and HWP1 genes were specific for C. albicans,
      while the ones for CAP1, CAT1, EFG1, LIP3, and PLB1 were detected in C. albicans
      and C. dubliniensis. After optimization, all primers presented a single peak on
      melt curves, correlation coefficient of ?1 and qPCR reaction efficiency of 90
      110%, with slope of ?-3.3. Therefore, these primers should be suitable for future
      gene expression analyses from clinical samples.

PMID- 29454004
TI  - Identification and analysis of peanut-specific effector T and regulatory T cells
      in children allergic and tolerant to peanut.
AB  - BACKGROUND: Peanut allergy (PA) is potentially life-threatening and generally
      persists for life. Recent data suggest the skin might be an important route of
      initial sensitization to peanut, whereas early oral exposure to peanut is
      protective. In mice regulatory T (Treg) cells are central to the development of
      food tolerance, but their contribution to the pathogenesis of food allergy in
      human subjects is less clear. OBJECTIVE: We sought to quantify and phenotype CD4+
      peanut-specific effector T (ps-Teff) cells and peanut-specific regulatory T (ps
      Treg) cells in children with and without PA or PS. METHODS: ps-Teff and ps-Treg
      cells were identified from peripheral blood of children with PA, children with
      PS, and nonsensitized/nonallergic (NA) school-aged children and 1-year-old
      infants based on upregulation of CD154 or CD137, respectively, after stimulation
      with peanut extract. Expression of cytokines and homing receptors was evaluated
      by using flow cytometry. Methylation at the forkhead box protein 3 (FOXP3) locus
      was measured as a marker of Treg cell stability. RESULTS: Differential
      upregulation of CD154 and CD137 efficiently distinguished ps-Teff and ps-Treg
      cells. A greater percentage of ps-Teff cells from infants with PA and infants
      with PS expressed the skin-homing molecule cutaneous lymphocyte antigen,
      suggesting activation after exposure through the skin, compared with NA infants.
      Although ps-Teff cells in both school-aged and infant children with PA produced
      primarily TH2 cytokines, a TH1-skewed antipeanut response was seen only in NA
      school-aged children. The frequency, homing receptor expression, and stability of
      ps-Treg cells in infants and school-aged children were similar, regardless of
      allergic status. CONCLUSIONS: Exposure to peanut through the skin can prime the
      development of TH2 ps-Teff cells, which promote sensitization to peanut, despite
      the presence of normal numbers of ps-Treg cells.

PMID- 29454006
TI  - Predicting cognitive decline with deep learning of brain metabolism and amyloid
      imaging.
AB  - For effective treatment of Alzheimer's disease (AD), it is important to identify
      subjects who are most likely to exhibit rapid cognitive decline. We aimed to
      develop an automatic image interpretation system based on a deep convolutional
      neural network (CNN) which can accurately predict future cognitive decline in
      mild cognitive impairment (MCI) patients using flurodeoxyglucose and florbetapir
      positron emission tomography (PET). PET images of 139 patients with AD, 171
      patients with MCI and 182 normal subjects obtained from Alzheimer's Disease
      Neuroimaging Initiative database were used. Deep CNN was trained using 3
      dimensional PET volumes of AD and normal controls as inputs. Manually defined
      image feature extraction such as quantification using predefined region-of
      interests was unnecessary for our approach. Furthermore, it used minimally
      processed images without spatial normalization which has been commonly used in
      conventional quantitative analyses. Cognitive outcome of MCI subjects was
      predicted using this network. The prediction accuracy of the conversion of mild
      cognitive impairment to AD was compared with the conventional feature-based
      quantification approach. Accuracy of prediction (84.2%) for conversion to AD in
      MCI patients outperformed conventional feature-based quantification approaches.
      ROC analyses revealed that performance of CNN-based approach was significantly
      higher than that of the conventional quantification methods (p < 0.05). Output
      scores of the network were strongly correlated with the longitudinal change in
      cognitive measurements (p < 0.05). These results show the feasibility of deep
      learning as a practical tool for developing predictive neuroimaging biomarker.

PMID- 29454007
TI  - Destruction of noradrenergic terminals increases dopamine concentration and
      reduces dopamine metabolism in the medial prefrontal cortex.
AB  - Effects of destroyed noradrenergic (NE) innervation in the medial prefrontal
      cortex (mPFC) were examined on dopamine (DA) content and metabolism. Six-hydroxy
      DOPA (6-OHDOPA) or 6-hydroxy-dopamine (6-OHDA) in combination with a potent DA
      reuptake inhibitor GBR 12935 or 6-OHDA were injected bilaterally into the mPFC in
      separate groups of animals. In addition, GBR 12935 or vehicle was injected into
      the mPFC in two other groups of animals as control experiments. NE and DA
      concentrations from postmortem tissue of the mPFC were measured using HPLC with
      electrochemical detection. In addition, extracellular NE, DA and DOPAC levels
      were determined using in vivo microdialysis after the 6-OHDA lesion in
      combination with GBR 12935 pretreatment in the mPFC. Using reverse microdialysis
      of alpha-2-adrenoreceptor antagonist yohimbine, we tested the remaining activity
      of NE innervation and the extracellular concentration of DA and DOPAC. NE and DA
      concentrations from postmortem tissue of the mPFC showed that 6-OHDOPA lesion
      reduced NE concentration to 76%, which was a non-significant alteration, however
      it enhanced significantly DA concentration to 186% compared to vehicle. After 6
      OHDA lesion with GBR 12935 pretreatment, concentration of NE significantly
      decreased to 51% and DA level increased to 180%. 6-OHDA lesion without GBR 12635
      pretreatment decreased NE concentration to 23% and DA concentration to 67%. In
      the microdialysis experiment, after 6-OHDA lesion with GBR 12935 pretreatment,
      extracellular NE levels were not detectable, whereas extracellular DA levels were
      increased and DOPAC levels were decreased compared to controls. Reverse
      microdialysis of yohimbine demonstrated that the residual NE innervation was able
      to increase NE level and DA levels, but DOPAC concentration remained low after
      lesion of the NE terminals. These findings suggest that the damage of NE
      innervation in the mPFC may alter extracellular DA level due to a reduced DA
      clearance.

PMID- 29454008
TI  - Temozolomide affects Extracellular Vesicles Released by Glioblastoma Cells.
AB  - Glioblastoma multiforme (GBM) is the most aggressive primary tumour within the
      brain as well as the most common and lethal cerebral cancer, mainly because of
      treatment failure. Indeed, tumour recurrence is inevitable and fatal in a short
      period of time. Glioblastoma stem-like cells (GSCs) are thought to participate in
      tumour initiation, expansion, resistance to treatments, including to the
      alkylating chemotherapeutic agent temozolomide, and relapse. Here, we assessed
      whether extracellular vesicles (EVs) released by GSCs could disseminate factors
      involved in resistance mechanisms. We first characterized EVs either circulating
      in peripheral blood from newly diagnosed patients or released by patient-derived
      temozolomide-resistant GSCs. We found that EVs from both sources were mainly
      composed of particles homogeneous in size (50-100 nm), while they were more
      abundant in liquid biopsies from GBM patients, as compared to healthy donors.
      Further, mass spectrometry analysis from GSC-derived EVs unveiled that particles
      from control and temozolomide-treated cells share core components of EVs, as well
      as ribosome- and proteasome-associated networks. More strikingly, temozolomide
      treatment led to the enrichment of EVs with cargoes dedicated to cell adhesion
      processes. Thus, while relatively inefficient in killing GSCs in vitro,
      temozolomide could instead increase the release of pro-tumoral information.

PMID- 29454010
TI  - Enhancing creative cognition with a rapid right-parietal neurofeedback procedure.
AB  - The present article describes an innovative neurofeedback training (NFT)
      procedure aimed at increasing creative cognition through the enhancement of
      specific brain activities previously associated with divergent thinking. We
      designed and tested two NFT protocols based on training alpha and beta EEG
      oscillations selectively measured over the right parietal region. A total of 80
      participants were involved, 40 in the alpha NFT protocol and 40 in the beta NFT
      protocol. The NFT loop was closed on a video stream that would advance only when
      oscillation power exceeded a normalized threshold. The total duration of the
      protocol was two hours in a single day, hence its classification as rapid.
      Changes in ideational fluency and originality, measured with a divergent thinking
      task, were compared between participants receiving real video feedback and
      participants receiving sham feedback. We controlled for individual differences in
      creative achievement level. Results showed that the protocols were effective at
      enhancing alpha and beta activities in the targeted area. Differences between the
      two protocols emerged in their effectiveness at promoting divergent thinking.
      While no significant changes in originality resulted from the rapid alpha NFT,
      increases in both originality and fluency emerged as a consequence of the rapid
      beta NFT. These results were particularly evident in participants starting with a
      low creative achievement level. Possible interpretations and future directions
      are proposed and discussed.

PMID- 29454011
TI  - Comparative study on some oxidative stress parameters in blood of vitiligo
      patients before and after combined therapy.
AB  - Currently accepted that oxidative stress is a triggering event in the melanocytic
      destruction and is probably involved in the etiopathogenesis of vitiligo disease.
      Despite numerous investigations, contradictory results were reported about the
      levels of oxidative stress biomarkers measured in the skin and blood of vitiligo
      patients. By Electron Paramagnetic Resonance spectroscopy (EPR) and
      spectrophotometry, we have investigated and compared some oxidative stress
      biomarkers in the blood of vitiligo patients' before and after UVB Narrow Band
      311 nm phototherapy combined with the antioxidant nutritional supplement
      containing - Vitamin C, Vitamin B1, L -Cysteine, Lipoic Acid, and polyunsaturated
      fatty acids. Before therapy was found significantly higher levels of CAT activity
      and MDA compared to the patients after therapy and control group (p < 0.05).
      Moreover, levels of Asc* radicals in patients before therapy were significantly
      lower than those measured in controls and patients undergoing therapy (p < 0.05).
      Our finding, the combined therapy applied to vitiligo patients provoked an
      increase in the Asc* levels and a decrease in MDA products and also initial
      repigmentation in the vitiligo spots, made us believe that a combined antioxidant
      therapy, enriched with vitamin C could lead to improvement of the oxidant
      antioxidant balance in vitiligo patients treated with UVB 311 phototherapy.

PMID- 29454009
TI  - 24 vs. 72 hours of hypothermia for pediatric cardiac arrest: A pilot, randomized
      controlled trial.
AB  - AIM: Children surviving cardiac arrest (CA) lack proven neuroprotective
      therapies. The role of biomarkers in assessing response to interventions is
      unknown. We hypothesized that 72 versus 24 h of hypothermia (HT) would produce
      more favorable biomarker profiles after pediatric CA. METHODS: This single center
      pilot randomized trial tested HT (33 +/- 1  degrees C) for 24 vs. 72 h in 34
      children with CA. Children comatose after return of circulation aged 1 week to 17
      years and treated with HT by their physician were eligible. Serum was collected
      twice daily on days 1-4 and once on day 7. Mortality was assessed at 6 months.
      RESULTS: Patient characteristics, baseline biomarker concentrations, and adverse
      events were similar between groups. Eight (47%) and 4 (24%) children died in the
      24 h and 72 h groups, p = .3. Serum neuron specific enolase (NSE) concentration
      was increased in the 24 vs. 72 h group at 84 h-96 h (median [interquartile range]
      47.7 [3.9, 79.9] vs. 1.4 [0.0, 11.1] ng/ml, p = .02) and on day 7 (18.2 [3.2,
      74.0] vs. 2.6 [0.0, 12.8] ng/ml, p = .047). Serum S100b was increased in the 24 h
      vs. 72 h group at 12 h-24 h, 36 h-84 h, and on day 7, all p < 0.05. HT duration
      was associated with S100b (but not NSE or MBP) concentration on day 7 in
      multivariate analyses. CONCLUSION: Serum biomarkers show promise as theragnostic
      tools in pediatric CA. Our biomarker and safety data also suggest that 72 h
      duration after pediatric CA warrants additional exploration.

PMID- 29454013
TI  - Implementation of an outcomes-based curriculum for dermatology clerkships and
      initial positive perceptions from faculty and students.

PMID- 29454012
TI  - Immunologic effects of chronic administration of tofacitinib, a Janus kinase
      inhibitor, in cynomolgus monkeys and rats - Comparison of juvenile and adult
      responses.
AB  - Tofacitinib, an oral Janus kinase (JAK) inhibitor for treatment of rheumatoid
      arthritis, targets JAK1, JAK3, and to a lesser extent JAK2 and TYK2. JAK1/3
      inhibition impairs gamma common chain cytokine receptor signaling, important in
      lymphocyte development, homeostasis and function. Adult and juvenile cynomolgus
      monkey and rat studies were conducted and the impact of tofacitinib on immune
      parameters (lymphoid tissues and lymphocyte subsets) and function (T-dependent
      antibody response (TDAR), mitogen-induced T cell proliferation) assessed.
      Tofacitinib administration decreased circulating T cells and NK cells in juvenile
      and adult animals of both species. B cell decreases were observed only in rats.
      These changes and decreased lymphoid tissue cellularity are consistent with the
      expected pharmacology of tofacitinib. No differences were observed between
      juvenile and adult animals, either in terms of doses at which effects were
      observed or differential effects on immune endpoints. Lymphomas were observed in
      three adult monkeys. Tofacitinib impaired the primary TDAR in juvenile monkeys,
      although a recall response was generated. Complete or partial reversal of the
      effects on the immune system was observed.

PMID- 29454014
TI  - Detecting structural and inflammatory response after in vivo stretch injury in
      the rat median nerve via second harmonic generation.
AB  - BACKGROUND: Second Harmonic Generation (SHG) microscopy is a promising method for
      visualizing the collagenous structure of peripheral nerves. Assessing collagen
      continuity and damage after a stretch injury provides inferential insight into
      the level of axonal damage present. NEW METHODS: This study utilizes SHG
      microscopy after a calibrated in vivo stretch injury of rat median nerves to
      evaluate collagen continuity at several time points throughout the recovery
      process. Endoneurial collagen was qualitatively assessed in nerves that were
      subjected to low strain (LS) and high strain (HS) injuries using SHG microscopy,
      conventional histology, and immunohistochemistry. RESULTS: Following an in vivo
      stretch injury, both LS and HS damaged nerves exhibit signs of structural
      collagen damage in comparison with sham control nerves (SC). Furthermore, LS
      nerves exhibit signs of full regeneration while HS nerves exhibited signs of only
      partial regeneration with lasting damage and intra-neural scar formation.
      COMPARISON WITH EXISTING METHODS: SHG observations of structural changes and
      inflammatory response due to stretch injury were validated upon comparison with
      conventional histological methods CONCLUSIONS: We propose that SHG microscopy can
      be utilized to visualize significant structural artifacts in sectioned median
      nerves following in vivo stretch injury. Based on the findings in this study, we
      believe that the in vivo application of SHG microscopy should be further
      investigated as a means for real-time, intra-operative, quantitative assessment
      of nerve damage.

PMID- 29454015
TI  - Why I eat at night: A qualitative exploration of the development, maintenance and
      consequences of Night Eating Syndrome.
AB  - Night Eating Syndrome (NES), as a diagnosis, presents as a combination of
      disordered eating, sleep and mood. Patients identified as having both NES and
      obesity demonstrate poorer outcomes in terms of weight loss compared to those
      with NES only. However, research focusing on psychological factors associated
      with NES remains relatively underdeveloped. This study aimed to explore the
      relationship between NES and the experience of emotion from the perspective of
      patients accessing a weight management service. Ten adults who met diagnostic
      criteria for moderate or full NES took part in a semi-structured interview. Data
      were analysed using a constructivist approach to grounded theory. A core concept
      to emerge from the analysis was termed 'emotional hunger'; reflecting an urge or
      need to satiate a set of underlying unmet emotional needs. It was underpinned by
      the following interrelated themes: (1) Cultivating a dependency on food; (2)
      Relying on food to regulate emotions; (3) Understanding the significance of night
      time; (4) Acknowledging the consequences of night eating. This study provides an
      in-depth understanding of the relationship between NES and the experience of
      emotion from the perspective of patients attending a weight management service.
      Results have potential to inform future service development, particularly around
      the adoption of a more holistic approach to night eating behaviours.

PMID- 29454016
TI  - Mother and child personality traits associated with common feeding strategies and
      child body mass index.
AB  - The feeding strategies that parents use with their children shape their
      children's attitudes and behaviors toward food. The present research examined
      whether personality traits of the mother and the child are associated with the
      types of feeding strategies mothers use with their children. The present research
      also examined whether these characteristics are associated with the child's body
      mass index (BMI). Mothers (N = 2928) reported how often they used three feeding
      strategies (Restriction, Pressure to Eat, Monitoring) with the target child and
      their personality and the personality of the child. Both mother and child
      Conscientiousness were associated significantly with less use of Restriction and
      Pressure to Eat and more use of Monitoring. Child Openness and Agreeableness were
      likewise related to less use of Restriction and Pressure to Eat. Mother and child
      Conscientiousness were associated with child obesity: Children with obesity
      scored lower in Conscientiousness and also had mothers who scored lower on this
      trait; Restriction and Pressure to Eat partially mediated the association between
      mother Conscientiousness and child BMI. The present findings suggest that
      individual differences in both mother and child personality are associated with
      the use of three common feeding strategies in childhood and the child's weight.

PMID- 29454017
TI  - A rapid method for titration of ascovirus infectivity.
AB  - Ascoviruses are a recently described family and the traditional plaque assay and
      end-point PCR assay have been used for their titration. However, these two
      methods are time-consuming and inaccurate to titrate ascoviruses. In the present
      study, a quick method for the determination of the titer of ascovirus stocks was
      developed based on ascovirus-induced apoptosis in infected insect cells. Briefly,
      cells infected with serial dilutions of virus (10-2-10-10) for 24 h were stained
      with trypan blue. The stained cells were counted, and the percentage of nonviable
      cells was calculated. The stained cell rate was compared between virus-infected
      and control cells. The minimum-dilution group that had a significant difference
      compared with control and the maximum-dilution group that had no significant
      difference were selected and then compared each well of the two groups with the
      average stained cell rate of control. The well was marked as positive well if the
      stained cell rate was higher than the average stained cell rate of control wells;
      otherwise, the well was marked as negative wells. The percentage of positive
      wells were calculated according to the number of positive. Subsequently, the
      virus titer was calculated through the method of Reed and Muench. This novel
      method is rapid, simple, reproducible, accurate, and less material-consuming and
      eliminates the subjectivity of the other procedures for titrating ascoviruses.

PMID- 29454018
TI  - Co-circulation of classic and novel astrovirus strains in patients with acute
      gastroenteritis in Germany.
AB  - OBJECTIVES: In order to analyze the molecular epidemiology of human astroviruses
      (HAstV) in Germany, a retrospective long-term study was performed to characterize
      circulating human astrovirus in patients with acute gastroenteritis in Germany.
      METHODS: A total of 2877 stool samples, collected between January 2010 and
      December 2015 from sporadic cases and outbreaks of acute gastroenteritis were
      retrospectively analyzed for astrovirus. A two-step PCR algorithm was developed
      and used to identify and characterize human astrovirus infections. RESULTS:
      Overall, 143 samples were astrovirus-positive (5.0%). Astrovirus infection was
      most frequently detectable in samples from children of 3-4 years (15%) followed
      by children of 1-2 years (8.6%), detection rates in adults were lower (1%-3.6%).
      A high number (71.3%) of co-infections, mainly with noro- or rotaviruses, were
      identified. Genotyping revealed that at least ten genotypes from all four human
      MAstV species were circulating in the study population. HAstV-1 was predominant
      in different age groups. Novel HAstV (MLB and VA genotypes) were also circulating
      in Germany. CONCLUSION: Our findings give new insights into the circulation and
      genetic diversity of human astroviruses in patients with acute gastroenteritis.
      The novel HAstV-MLB and -VA genotypes could be characterized firstly in Germany
      while the analysis showed that these viruses have been dispersed in Germany since
      2011 as a causative agent of acute gastroenteritis.

PMID- 29454019
TI  - Channelopathies go above and beyond the channels.

PMID- 29454020
TI  - Variation of the alkaloid content of Peumus boldus (boldo).
AB  - Eighteen alkaloids were detected in the bark, leaves, wood and roots of Peumus
      boldus, including traces of secoboldine, N-methylsecoboldine (boldine methine),
      glaucine and norreticuline, not reported previously as constituents of this
      species. Using appropriate standards, we quantified thirteen of them by UHPLC
      MS/MS. Boldine was dominant in the bark, and laurolitsine in wood and roots. The
      alkaloid composition of the leaves, determined for 130 individually identified
      trees, classified by age and sex, was highly variable, where N
      methyllaurotetanine, laurotetanine, coclaurine and in some cases isocorydine
      predominated, but not boldine.

PMID- 29454021
TI  - Three new quinazolines from Evodia rutaecarpa and their biological activity.
AB  - In this research, we investigated the profile and bioactivities of quinazoline
      alkaloids, a class of natural products boasting multiple bioactivities, from the
      unripe fruit of Evodia rutaecarpa (Juss.) Benth. Three new quinazoline alkaloids,
      evodiamide A (1), evodiamide B (2), and evodiamide C (3), as well as eight known
      quinazolines, were isolated from the MeOH extract of E. rutaecarpa. The new
      compounds are rare quinazolinedione derivatives with linked heterocyclic nuclei.
      Among these quinazolines, rhetsinine (8) showed potential as a pesticide and
      exhibited excellent inhibition against Xanthomonas oryzae pv. oryzae, Xanthomonas
      oryzae pv. oryzicola, and Xanthomonas campestris pv. campestris, with respective
      EC50 values of 3.13, 14.32, and 32.72 nmol.

PMID- 29454022
TI  - Five new schinortriterpenoids from Schisandra propinqua var. propinqua.
AB  - Five new schinortriterpenoids, propinqtrilactones A and B (1 and 2) with rare
      lancischiartane scaffold, and propindilactones V-X (3-5), were isolated from the
      stems and leaves of Schisandra propinqua var. propinqua. Their structures were
      elucidated on the basis of comprehensive spectroscopic and mass spectrometric
      analysis. The absolute configurations of 1-5 were determined by CD methods, X-ray
      diffraction analysis and theoretical calculations. 4 was tested for its cytotoxic
      activities against five human tumor cell lines.

PMID- 29454023
TI  - Interaction between hypothermia and delayed mesenchymal stem cell therapy in
      neonatal hypoxic-ischemic brain injury.
AB  - Acute hypothermia treatment (HT) is the only clinically established intervention
      following neonatal hypoxic-ischemic brain injury. However, almost half of all
      cooled infants still die or suffer from long-lasting neurological impairments.
      Regenerative therapies, such as mesenchymal stem cells (MSC) appear promising as
      adjuvant therapy. In the present study, we hypothesized that HT combined with
      delayed MSC therapy results in augmented protection, improving long-term
      neurological outcome. Postnatal day 9 (P9) C57BL/6 mice were exposed to hypoxia
      ischemia followed by 4 h HT. Murine bone marrow-derived MSC (1 * 106
      cells/animal) were administered intranasally at P12. Cytokine and growth factor
      levels were assessed by ELISA and Luminex(r) multiplex assay 24 h following MSC
      delivery. One week after HI, tissue injury and neuroinflammatory responses were
      determined by immunohistochemistry and western blot. Long-term motor-cognitive
      outcome was assessed 5 weeks post injury. MSC responses to the brains'
      environment were evaluated by gene expression analysis in MSC, co-cultured with
      brain homogenates isolated at P12. Both, MSC and HT improved motor deficits,
      while cognitive function could only be restored by MSC. Compared to each single
      therapy, combined treatment led to increased long-lasting motor-cognitive
      deficits and exacerbated brain injury, accompanied by enhanced endothelial
      activation and peripheral immune cell infiltration. MSC co-cultured with brain
      extracts of HT-treated animals revealed increased pro-inflammatory cytokine and
      decreased growth factor expression. In vivo protein analysis showed higher pro
      inflammatory cytokine levels after combined treatment compared to single therapy.
      Furthermore, HI-induced increase in growth factors was normalized to control
      levels by HT and MSC single therapy, while the combination induced a further
      decline below control levels. Our results suggest that alteration of the brains'
      microenvironment by acute HT modulates MSC function resulting in a pro
      inflammatory environment combined with alteration of the homeostatic growth
      factor milieu in the neonatal hypoxic-ischemic brain. This study delineates
      potential unexpected side effects of cell-based therapies as add-on therapy for
      acute hypothermia treatment.

PMID- 29454025
TI  - Early alteration of distribution and activity of hippocampal type-1 cannabinoid
      receptor in Alzheimer's disease-like mice overexpressing the human mutant amyloid
      precursor protein.
AB  - Besides its involvement in Alzheimer's disease (AD) as precursor of the
      neurotoxic amyloid peptides, the pathophysiological impact of brain accumulation
      of amyloid precursor protein (APP) is not yet well understood. Recent studies
      reported that APP interacts with other membrane proteins, including G protein
      coupled receptors, affecting their biological functions. Here, we focused on the
      study of the potential impact of human mutant APP on expression, distribution and
      activity of type-1 cannabinoid (CB1) receptor in the hippocampus of Tg2576 mice,
      an AD-like mice model. By using biochemical and electrophysiological measures, we
      found that in a presymptomatic phase, when amyloid plaques have not yet formed
      and there is no sign of cognitive deficits, the over-expression of full-length
      APP in the hippocampus of Tg2576 mice altered membrane localization and
      inhibitory signalling activity of CB1 receptor, possibly by binding to the
      receptor and reducing its specific interaction with caveolin-1 and G proteins.

PMID- 29454024
TI  - Development of an in vitro screening method of acute cytotoxicity of the
      pyrrolizidine alkaloid lasiocarpine in human and rodent hepatic cell lines by
      increasing susceptibility.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pyrrolizidine alkaloids (PAs) are secondary plant
      ingredients formed in many plant species to protect against predators. PAs are
      generally considered acutely hepatotoxic, genotoxic and carcinogenic. Up to now,
      only few in vitro and in vivo investigations were performed to evaluate their
      relative toxic potential. AIM OF THE STUDY: The aim was to develop an in vitro
      screening method of their cytotoxicity. MATERIALS AND METHODS: Human and rodent
      hepatocyte cell lines (HepG2 and H-4-II-E) were used to assess cytotoxicity of
      the PA lasiocarpine. At concentrations of 25 uM up to even 2400 uM, no toxic
      effects in neither cell line was observed with standard cell culture media.
      Therefore, different approaches were investigated to enhance the susceptibility
      of cells to PA toxicity (using high-glucose or galactose-based media, induction
      of toxifying cytochromes, inhibition of metabolic carboxylesterases, and
      inhibition of glutathione-mediated detoxification). RESULTS: Galactose-based
      culture medium (11.1 mM) increased cell susceptibility in both cell-lines.
      Cytochrome P450-induction by rifampicin showed no effect. Inhibition of
      carboxylesterase-mediated PA detoxification by specific carboxylesterase 2
      inhibitor loperamide (2.5 uM) enhanced lasiocarpine toxicity, whereas the
      unspecific carboxylesterase inhibitor bis(4-nitrophenyl)phosphate (BNPP, 100 uM))
      had a weaker effect. Finally, the inhibition of glutathione-mediated
      detoxification by buthionine sulphoximine (BSO, 100 uM) strongly enhanced
      lasiocarpine toxicity in H-4-II-E cells in low and medium, but not in high
      concentrations. CONCLUSIONS: If no toxicity is observed under standard
      conditions, susceptibility enhancement by using galactose-based media,
      loperamide, and BSO may be useful to assess relative acute cytotoxicity of PAs in
      different cell lines.

PMID- 29454027
TI  - Selection of biomarkers for HIV-1 latency by integrated analysis.
AB  - A major obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1)
      is its ability to establish latent infection. To find novel biomarkers associated
      with the mechanism of HIV-1 latent infection, we identified 70 candidate genes in
      HIV-1 latently infected cells through the integrated analysis in a previous
      study. It is important to select more effective biomarkers among 70 candidates
      and to verify the possibility of selected biomarkers for HIV-1 latency. We
      identified the 24 and 25 genes from 70 candidate genes in significantly enriched
      categories selected by Database for Annotation, Visualization and Integrated
      Discovery (DAVID) software and Gene Set Enrichment Analysis (GSEA) software,
      respectively. Also, we investigated genes regulated in both HIV-1 latently
      infected cell lines and PBMCs from HIV-1 infected patients and found the genes
      with a common pattern of expression levels in both cell lines and PBMCs.
      Consequently, we identified nine genes, APBB2, GMPR, IGF2BP3, LRP1, MAD2L2, MX1,
      OXR1, PTK2B, and TNFSF13B, via integrated analysis. Especially, APBB2 and MAD2L2
      were identified in both DAVID and GSEA software. Our findings suggest that nine
      genes were identified via integrated analysis as potential biomarkers and in
      particular, APBB2 and MAD2L2 may be considered as more significant biomarkers for
      HIV-1 latency.

PMID- 29454026
TI  - Adaptation of Escherichia coli to long-term batch culture in various rich media.
AB  - Experimental evolution studies have characterized the genetic strategies microbes
      utilize to adapt to their environments, mainly focusing on how microbes adapt to
      constant and/or defined environments. Using a system that incubates Escherichia
      coli in different complex media in long-term batch culture, we have focused on
      how heterogeneity and environment affects adaptive landscapes. In this system,
      there is no passaging of cells, and therefore genetic diversity is lost only
      through negative selection, without the experimentally-imposed bottlenecking
      common in other platforms. In contrast with other experimental evolution systems,
      because of cycling of nutrients and waste products, this is a heterogeneous
      environment, where selective pressures change over time, similar to natural
      environments. We determined that incubation in each environment leads to
      different adaptations by observing the growth advantage in stationary phase
      (GASP) phenotype. Re-sequencing whole genomes of populations identified both
      mutant alleles in a conserved set of genes and differences in evolutionary
      trajectories between environments. Reconstructing identified mutations in the
      parental strain background confirmed the adaptive advantage of some alleles, but
      also identified a surprising number of neutral or even deleterious mutations.
      This result indicates that complex epistatic interactions may be under positive
      selection within these heterogeneous environments.

PMID- 29454028
TI  - Fabricating 3D printed orally disintegrating printlets using selective laser
      sintering.
AB  - Selective laser sintering (SLS) is a three-dimensional printing (3DP) technology
      employed to manufacture plastic, metallic or ceramic objects. The aim of this
      study was to demonstrate the feasibility of using SLS to fabricate novel solid
      dosage forms with accelerated drug release properties, and with a view to create
      orally disintegrating formulations. Two polymers (hydroxypropyl methylcellulose
      (HPMC E5) and vinylpyrrolidone-vinyl acetate copolymer (Kollidon(r) VA 64)) were
      separately mixed with 5% paracetamol (used as a model drug) and 3% Candurin(r)
      Gold Sheen colorant; the powder mixes were subjected to SLS printing, resulting
      in the manufacture of printlets (3DP tablets). Modulating the SLS printing
      parameters altered the release characteristics of the printlets, with faster
      laser scanning speeds accelerating drug release from the HPMC formulations. The
      same trend was observed for the Kollidon(r) based printlets. At a laser scanning
      speed of 300 mm/s, the Kollidon(r) printlets exhibited orally disintegrating
      characteristics by completely dispersing in <4 s in a small volume of water. X
      ray micro-CT analysis of these printlets indicated a reduction in their density
      and an increase in open porosity, therefore, confirming the unique disintegration
      behaviour of these formulations. The work reported here is the first to
      demonstrate the feasibility of SLS 3DP to fabricate printlets with accelerated
      drug release and orally disintegrating properties. This investigation has
      confirmed that SLS is amenable to the pharmaceutical research of modern medicine
      manufacture.

PMID- 29454029
TI  - Sex-related differences in the association between grip strength and depression:
      Results from the Irish Longitudinal Study on Ageing.
AB  - Muscular strength is a modifiable protective factor for mental health across
      aging populations. Evidence of sex-related differences in its associations with
      mental health is limited. Therefore, the purpose of this study was to examine sex
      related differences in cross-sectional and prospective associations between grip
      strength and depressive symptoms and status. Participants were community dwelling
      adults (N = 4505; 56.5% female), aged >=50 years. As a measure of muscular
      strength, grip strength (kg) of the dominant hand was assessed using a hand-held
      dynamometer at baseline. Participants were divided into sex-specific tertiles.
      The Center for Epidemiological Studies Depression Scale assessed depressive
      symptoms at baseline and two years later; a score of >=16 defined caseness of
      depression. Depressive symptoms were significantly higher among females at
      baseline (p < 0.001). Prospective models were adjusted for age, sex, waist
      circumference, social class, smoking, and health status. Among males, the middle
      and high strength tertiles were non-significantly associated with 32.9% (p =
      0.21) and 9.9% (p = 0.74) reduced odds of developing depression, respectively.
      Among females, the middle and high strength tertiles were non-significantly
      associated with 28.5% (p = 0.13) and significantly associated with 43.4% (p =
      0.01) reduced odds of developing depression, respectively. In the total sample,
      the middle and high strength tertiles were significantly associated with 31.5% (p
      = 0.04) and 34.1% (p = 0.02) reduced odds of developing depression, respectively.
      The interaction between sex and strength was not statistically significant (p =
      0.25). The present findings indicated that grip strength was inversely associated
      with incident depression in older adults, with stronger associations observed
      among females than males.

PMID- 29454030
TI  - Using decision thresholds for ranking treatments in network meta-analysis results
      in more informative rankings.
AB  - OBJECTIVES: To evaluate how the rank probabilities obtained from network meta
      analysis (NMA) change with the use of increasingly stringent criteria for the
      relative effect comparing two treatments which ranks one treatment better than
      the other. STUDY DESIGN AND SETTING: Systematic survey and reanalysis of
      published data. We included all systematic reviews (SRs) with NMA from the field
      of cardiovascular medicine that had trial-level data available, published in
      Medline up to February 2015. We reran all the NMAs and determined the
      probabilities of each treatment being the best. For the best treatment, we
      examined the effect on these probabilities of varying, what we call the decision
      threshold, the relative effect required to declare two treatments different.
      RESULTS: We included 14 SRs, having a median of 20 randomized trials and 9
      treatments. The best treatments had probabilities of being best that ranged from
      38% to 85.3%. The effect of changing the decision thresholds on the probability
      of a treatment being best varied substantially across reviews, with relatively
      little decrease (~20 percentage points) in some settings but a decline to near 0%
      in others. CONCLUSION: Rank probabilities can be fragile to increases in the
      decision threshold used to claim that one treatment is more effective than
      another. Including these thresholds into the calculation of rankings may aid
      their interpretation and use in clinical practice.

PMID- 29454031
TI  - Expression and characterization of recombinant rattusin, an alpha-defensin
      related peptide with a homodimeric scaffold formed by intermolecular disulfide
      exchanges.
AB  - Rattusin is an alpha-defensin-related peptide isolated from the small intestine
      of rats. The primary sequence of linear rattusin is composed of 31 amino acids
      containing five cysteines with a unique spacing pattern. It forms a homodimeric
      scaffold in which the primary structure occurs in an antiparallel fashion formed
      by five intermolecular disulfide (SS) bonds. Rattusin is a highly potent
      antibiotic, which not only exhibits broad-spectrum antimicrobial activity, but
      also maintains its antimicrobial activity at physiological salt concentrations.
      Therefore, to develop new antibiotics based on rattusin, structural and
      functional studies of rattusin should be performed. For this purpose, large
      amounts of linear rattusin precursor must be obtained through appropriate
      preparation methods. Therefore, we established a mass production technique for
      linear rattusin by using recombinant protein expression and purification
      procedures. We verified that structure and activity of the recombinant rattusin
      are identical to the chemically synthesized rattusin. The described method for
      producing recombinant rattusin provides a high yield of rattusin, which can be
      used to study the biochemical and functional properties of rattusin and for the
      development of rattusin-based peptide antibiotics.

PMID- 29454032
TI  - Basal polarization of the immune responses to Streptococcus agalactiae
      susceptible and resistant tilapia (Oreochromis niloticus).
AB  - One of the highest priority areas for improvement is the development of effective
      strategies for decreasing disease mortality levels in aquaculture production, a
      better understanding of the components of the fish immune system and their
      functions in the context of pathogen invasion is needed. Tilapia is the most
      common fish in South China, and Streptococcus agalactiae has become the most
      serious disease problem for tilapia industry in China. Here, we profiled gene
      expression differences between tilapia differing in their susceptibility to S.
      agalactiae both basally (before infection) and at three early timepoints post
      infection (5 h, 50 h, and 7 d). Between group comparisons revealed 5756 unique
      genes differentially expressed greater than 2-fold at one or more timepoints. And
      the resistant fish showed much more strong ability in pathogen recognition,
      antigen presentation, immune activation, while the susceptible fish showed fast
      activation of apoptosis. Taken together, the immune profiles expand our knowledge
      for molecular mechanisms for disease resistance, as well as provide solid
      molecular resources for further identification of the candidate markers for
      disease-resistant selection and evaluation of disease prevention and treatment
      options for tilapia industry.

PMID- 29454033
TI  - Cause or Coincidence? Spontaneous Hematometra in Young Women Receiving
      Depomedroxyprogesterone Acetate: A Small Case Series.
AB  - BACKGROUND: Abdominal pain, secondary amenorrhea, and abnormal uterine bleeding
      are common gynecologic presentations in adolescence. Rarely this can be
      associated with an acquired hematometra. Hematometra is a condition of retained
      blood or clot within the uterus. High-dose progestogenic agents in this age group
      have been implicated in the accumulation of a hematometra without other
      explanation. CASES: We present 4 cases of hematometra after
      depomedroxyprogesterone acetate (DMPA) therapy in previously menstruating
      adolescents. All 4 presented with abdominal pelvic pain and/or persistent
      abnormal uterine bleeding, with the diagnosis confirmed via ultrasound. Suction
      dilation and curettage was required in each case. SUMMARY AND CONCLUSION: DMPA is
      a possible cause of hematometra and should be considered in anatomically normal
      young women experiencing pain or abnormal bleeding out of character for typical
      long-term DMPA use.

PMID- 29454034
TI  - Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral
      prefrontal cortex in depressive episodes of patients with major depressive
      disorder, bipolar disorder I, and major depressive with alcohol use disorders.
AB  - BACKGROUND: Dorsolateral prefrontal cortex (DLPFC) is critically involved in mood
      and alcohol use disorders. OBJECTIVE: We aimed to investigate the safety of
      intervention with add-on bilateral prefrontal high-frequency deep transcranial
      magnetic stimulation (dTMS) and between-group differences in treatment response
      in patients with different types of depressive episodes, including major
      depressive episodes in the course of major depressive disorder (MDD), bipolar
      disorder, type I (BD-I), and MDD with alcohol use disorder (MDAUD). METHODS: We
      conducted a 6-month open-label study, involving 82 patients with DSM-5 Depressive
      Episode. Of these, 41 had diagnosis of MDD, 20 BD-I, and 21 MDAUD. All patients
      received standard drug treatment and add-on dTMS over the bilateral DLPFC with
      left prevalence for four weeks, with five sessions in each week. We rated mood
      state with the Hamilton Depression Rating Scale (HDRS) at baseline, one-month,
      and six-month follow-up visits. RESULTS: Mean total HDRS scores dropped from 22.8
      (SD = 5.9) at baseline to 10.4 (SD = 3.6) at 1 month, to 10.0 (SD = 4.5) at 6
      months, while response/remission were 70.73% (N = 58) and 19.51% (N = 16) at 1
      month and 76.83% (N = 63) and 32.93% (27) at 6 months, respectively, with no
      between-group differences. No patient experienced any side effects. CONCLUSIONS:
      High-frequency DLPFC dTMS was well tolerated and did not significantly differ on
      improvement of depression in MDD, BD-I, and MDAUD.

PMID- 29454035
TI  - High and low doses of cocaine intake are differentially regulated by dopamine D2
      receptors in the ventral tegmental area and the nucleus accumbens.
AB  - Dopamine D2 receptors (D2Rs) in the ventral tegmental area (VTA) and the nucleus
      accumbens (NAc) are associated with vulnerability to addiction; however, whether
      D2Rs in these two brain regions play differential roles in regulation of drug
      intake is unknown. Here, we compared the effect of decreased mRNA level of Drd2
      in each region on cocaine self-administration in a dose-response function. Drd2
      mRNA levels in rat VTA or NAc were knocked down by bilateral microinjection of
      lentivirus coding shRNAs against rat Drd2 or scrambled shRNA. Drd2 knockdown was
      persistent and stable between 20 and 90 days after lentiviral infection. Animals
      were trained to self-administer cocaine 20 days after Drd2 shRNA treatment.
      Compared to scrambled shRNA treated rats, Drd2 knockdown in the VTA increased
      cocaine self-administration at all tested doses (0.02-0.56 mg/kg/infusion)
      producing an upward shift (both the ascending and descending limb) in the dose
      response curve of cocaine self-administration. In contrast, intra-NAc knockdown
      increased cocaine self-administration only on the ascending limb of the dose
      response curve (0.02-0.07 mg/kg/infusion). These data suggest that D2Rs in the
      VTA, not in the NAc, regulate high-dose cocaine intake. The present study not
      only demonstrates that low levels of D2Rs in either region increase low doses of
      cocaine intake, but also reveals for the first time their dissociable roles in
      limiting high doses of cocaine self-administration.

PMID- 29454036
TI  - Percutaneous Endovenous Intervention Plus Anticoagulation versus Anticoagulation
      Alone for Treating Patients with Proximal Deep Vein Thrombosis: A Meta-analysis
      and Systematic Review.
AB  - BACKGROUND: Combination treatment with percutaneous endovenous intervention
      (PEVI) and anticoagulation has been proposed for treating lower-extremity
      proximal deep vein thrombosis (DVT). We performed a systematic review and meta
      analysis of randomized controlled trials (RCTs) to assess the effect of PEVI plus
      anticoagulation versus anticoagulation alone in patients with lower-extremity
      proximal DVT. METHODS: We systematically searched PubMed, Embase, and the
      Cochrane Library from inception to May 2016. All RCTs comparing clinical outcomes
      between additional PEVI and anticoagulation alone were included. The main end
      points were postthrombotic syndrome (PTS) and major bleeding complications.
      Secondary outcomes included the iliofemoral patency rate, venous obstruction, and
      recurrent DVT. We assessed pooled data using a random-effects model. RESULTS:
      Four RCTs were included. PEVI plus standard anticoagulation compared with
      anticoagulation alone was associated with a lower rate of PTS (odds ratio [OR]
      0.34, 95% confidence interval [CI] 0.18-0.63), significantly higher iliofemoral
      patency rate at 6 months and 12 months (OR 8.49, 95% CI 1.32-54.60), a lower rate
      of venous obstruction (OR 0.42, 95% CI 0.20-0.924), and a lower rate of recurrent
      DVT (OR 0.42, 95% CI 0.20-0.92). However, more major bleeding episodes occurred
      in the group with catheter-directed thrombolysis (Peto OR 5.86, 95% CI 1.76
      19.48). CONCLUSIONS: PEVI plus anticoagulation reduced the occurrence of PTS,
      recurrent DVT, and venous obstruction. Another advantage is an increased patency
      rate at 6 and 12 months. The disadvantage is an increased occurrence of major
      bleeding events.

PMID- 29454037
TI  - Melatonin attenuates Delta9-tetrahydrocannabinol-induced reduction in rat sperm
      motility and kinematics in-vitro.
AB  - The use of Cannabis sativa (CS) has been widely demonstrated to have detrimental
      effect on male reproductive functions. Despite the well-known existence of
      endocannabinoid and melatonergic systems in semen, the physiological significance
      of their interaction is not understood. We recently showed that melatonin
      exacerbates the CS-induced gonadotoxicity in-vivo. To overcome the limitations
      associated with our in-vivo studies and further understand the role of
      cannabinoid-melatonin relationship in sperm functions, this study investigated
      the in-vitro effect of tetrahydrocannabinol (THC) and/or melatonin on motility
      and kinematics of capacitating rat sperms. Rat semen was randomly divided into 9
      treatment groups (n = 5) as follow: Groups 1-4 were treated with placebo,
      SR141716 (1 mM), AM-630 (1 mM), and THC (1 mM) respectively. Groups 5-7 were pre
      treated with SR141716, AM-630, and their combination respectively, followed by
      THC after 5 min. Group 8 was treated with melatonin (5 mM), while group 9 was
      treated with THC and melatonin. THC-induced reduction in sperm motility and
      kinematics were partly inhibited by cannabinoid receptor (CB) 1 or 2 blockade,
      but abolished by blockade of both CBs. Interestingly, melatonin increased the
      progressive motility and kinematics of rat sperms when administered alone and
      also attenuated THC-induced reduction in progressive motility (by 42%) and
      kinematics. The hyper-activated motility of capacitated sperms treated with
      cannabinoids and/or melatonin is determined largely by sperm velocities,
      amplitude of lateral head and beat/cross frequency but less by velocity ratios.
      Conclusively, the spermatotoxic effect of THC is mediated by CBs 1 and 2 and is
      ameliorated by melatonin in-vitro.

PMID- 29454038
TI  - Dendritic cells as cancer therapeutics.
AB  - The ability of immune therapies to control cancer has recently generated intense
      interest. This therapeutic outcome is reliant on T cell recognition of tumour
      cells. The natural function of dendritic cells (DC) is to generate adaptive
      responses, by presenting antigen to T cells, hence they are a logical target to
      generate specific anti-tumour immunity. Our understanding of the biology of DC is
      expanding, and they are now known to be a family of related subsets with variable
      features and function. Most clinical experience to date with DC vaccination has
      been using monocyte-derived DC vaccines. There is now growing experience with
      alternative blood-derived DC derived vaccines, as well as with multiple forms of
      tumour antigen and its loading, a wide range of adjuvants and different modes of
      vaccine delivery. Key insights from pre-clinical studies, and lessons learned
      from early clinical testing drive progress towards improved vaccines. The
      potential to fortify responses with other modalities of immunotherapy makes
      clinically effective "second generation" DC vaccination strategies a priority for
      cancer immune therapists.

PMID- 29454039
TI  - Effect of long-term selenium supplementation on mortality: Results from a
      multiple-dose, randomised controlled trial.
AB  - BACKGROUND: Selenium, an essential trace element, is incorporated into
      selenoproteins with a wide range of health effects. Selenoproteins may reach
      repletion at a plasma selenium concentration of ~ 125 ug/L, at which point the
      concentration of selenoprotein P reaches a plateau; whether sustained
      concentrations higher than this are beneficial, or indeed detrimental, is
      unknown. OBJECTIVE: In a population of relatively low selenium status, we aimed
      to determine the effect on mortality of long-term selenium supplementation at
      different dose levels. DESIGN: The Denmark PRECISE study was a single-centre,
      randomised, double-blinded, placebo-controlled, multi-arm, parallel clinical
      trial with four groups. Participants were 491 male and female volunteers aged 60
      74 years, recruited at Odense University Hospital, Denmark. The trial was
      initially designed as a 6-month pilot study, but supplemental funding allowed for
      extension of the study and mortality assessment. Participants were randomly
      assigned to treatment with 100, 200, or 300 ug selenium/d as selenium-enriched
      yeast or placebo-yeast for 5 years from randomization in 1998-1999 and were
      followed up for mortality for a further 10 years (through March 31, 2015).
      RESULTS: During 6871 person-years of follow-up, 158 deaths occurred. In an
      intention-to-treat analysis, the hazard ratio (95% confidence interval) for all
      cause mortality comparing 300 ug selenium/d to placebo was 1.62 (0.66, 3.96)
      after 5 years of treatment and 1.59 (1.02, 2.46) over the entire follow-up
      period. The 100 and 200 ug/d doses showed non-significant decreases in mortality
      during the intervention period that disappeared after treatment cessation.
      Although we lacked power for endpoints other than all-cause mortality, the
      effects on cancer and cardiovascular mortality appeared similar. CONCLUSIONS: A
      300 ug/d dose of selenium taken for 5 years in a country with moderately-low
      selenium status increased all-cause mortality 10 years later. While our study was
      not initially designed to evaluate mortality and the sample size was limited, our
      findings indicate that total selenium intake over 300 ug/d and high-dose selenium
      supplements should be avoided.

PMID- 29454042
TI  - When Do You Start and When Do You Stop Screening for Colon Cancer in Inflammatory
      Bowel Disease?

PMID- 29454040
TI  - Development of an Unrelated Donor Selection Score Predictive of Survival after
      HCT: Donor Age Matters Most.
AB  - Donor factors, in addition to HLA matching status, have been associated with
      recipient survival in unrelated donor (URD) hematopoietic cell transplantation
      (HCT); however, there is no hierarchical algorithm that weights the
      characteristics of individual donors against each other in a quantitative manner
      to facilitate donor selection. The goal of this study was to develop and validate
      a donor selection score that prioritizes donor characteristics associated with
      better survival in 8/8 HLA-matched URDs. Two separate patient/donor cohorts, the
      first receiving HCT between 1999 and 2011 (n = 5952, c1), and the second between
      2012 and 2014 (n = 4510, c2) were included in the analysis. Both cohorts were
      randomly spilt, 2:1, into training and testing sets. Despite studying over 10,000
      URD transplants, we were unable to validate a donor selection score. The only
      donor characteristic associated with better survival was younger age, with 2-year
      survival being 3% better when a donor 10 years younger is selected. These results
      support previous studies suggesting prioritization of a younger 8/8 HLA-matched
      donor. This large dataset also shows that none of the other donor clinical
      factors tested were reproducibly associated with survival, and hence flexibility
      in selecting URDs based on other characteristics is justified. These data support
      a simplified URD selection process and have significant implications for URD
      registries.

PMID- 29454041
TI  - Potential risks of Zika and chikungunya outbreaks in Brazil: A modeling study.
AB  - OBJECTIVES: While Brazil has witnessed an unprecedented Zika (ZIK) epidemic,
      chikungunya (CHIK) has also recently come into prominence as a threat in the
      Americas. The aim of this study was to identify the regions with increased
      probabilities of ZIK and CHIK occurrence, based on environmental and social
      conditions. METHODS: A statistical Maxent model was used to assess the potential
      spatial risk of ZIK and CHIK dissemination; this considered the number of
      probable autochthonous ZIK and CHIK cases in 2015 and 2016, along with
      environmental variables and social indicators. RESULTS: Land use was the most
      significant variable that best defined the distribution of ZIK and CHIK. Of the
      social variables, garbage destination, type of sanitary installation, and pipe
      borne water were the most significant. An estimated 65 million people in Brazil
      live in areas at high risk of ZIK and 75 million people in areas at high risk of
      CHIK. The southeast and northeast regions of Brazil presented the largest areas
      of high risk for both ZIK and CHIK. CONCLUSIONS: Many areas across the Brazilian
      territory are exposed to ZIK or CHIK infection risks, which are related mainly to
      land use. The study findings offer valuable information to support time-sensitive
      public health decision-making at the local and national levels.

PMID- 29454043
TI  - What Is the Role of the Inflammatory Bowel Disease Panel in Diagnosis and
      Treatment?

PMID- 29454045
TI  - Transforaminal en bloc resection for the treatment of thoracic ossification of
      the ligamentum flavum: Retrospective cohort study.
AB  - BACKGROUND: Our purpose is to introduce transforaminal en bloc resection for the
      treatment of thoracic ossification of ligamentum flavum, and report outcomes of
      the procedure. PATIENTS AND METHODS: The record of patients with symptomatic
      thoracic ossification of the ligamentum flavum who received transforaminal en
      block resection from October 2010 to September 2014 were retrospectively
      reviewed. Outcomes were Japanese Orthopaedic Association (JOA) lower extremity
      motor dysfunction and sphincter dysfunction scores. RESULTS: Seventeen patients
      (10 males, 7 females) with a median age of 60 years were included in the
      analysis. Surgery was performed as planned without complications in all patients.
      One segment decompression was performed in 1 case, 2 segment in 9 cases, 3
      segment in 3 cases, and 4 segment in 4 cases. The median lower extremity motor
      dysfunction score was significantly higher at 2 weeks, 3 months, and 6 months
      postoperatively, and the end of follow-up, than before surgery (median score: 2,
      2, 3, 3, respective, vs. 1, all, p <= 0.008). There were no significant
      differences in JOA sphincter dysfunction score between the different time points.
      CONCLUSION: Transforaminal en bloc resection is a safe and effective method for
      the treatment of thoracic ossification of the ligamentum flavum.

PMID- 29454044
TI  - The expression patterns of vestigial like family member 4 genes in zebrafish
      embryogenesis.
AB  - Transcriptional cofactor Vestigial-like 4 (VGLL4) was considered to take part in
      the early stage of development. Different from human, three paralogs of vgll4
      were found in zebrafish, which were vgll4a, vgll4b and vgll4l. However, the
      expression patterns of the three paralogs during zebrafish development remains
      unknown. In this study, we used in situ hybridization to elucidate the temporal
      and spatial expression of zebrafish vgll4 paralogs during normal embryonic and
      larval development. Similar expression was shown in certain areas at similar
      stages for the three paralogs. Expression of vgll4a, vgll4b and vgll4l were all
      found in pectoral fins and otic vesicles during the early developmental stages.
      On the other hand, a few differences of the three paralogs expression were found
      in eyes, pharynx, pharyngeal arches and brain tissues. The expression of vgll4a
      was weak and ubiquitous, while vgll4b was obviously expressed in brain tissues
      and vgll4l was clearly restricted to each pair of pharyngeal pouches. What's
      more, vgll4b and vgll4l had unique expression at mature lateral line neuromasts
      and forerunner cells respectively. Despite the conservativeness of functional
      domains, the three paralogs of zebrafish vgll4 shared several similarities and
      displayed some distinctions in the expression patterns, indicating that they may
      still have different and exclusive functions, which need to be further explored.

PMID- 29454046
TI  - The Psychometric Properties of the MBPS Scale Used to Assess Procedural Pain.
AB  - : The Modified Behavioral Pain Scale (MBPS) was designed to assess procedural
      pain in infants and is considered valid for assessing immunization pain. The aim
      of this study was to assess the practical and psychometric properties of the MBPS
      when applied to other commonly performed procedures. Twenty-six clinicians
      independently applied the MBPS scale to segments of video collected from 100
      infants and children aged 6 to 42 months undergoing 1 of 4 procedures in the
      emergency department. Positive correlation between MBPS and Visual Analogue Scale
      observer applied (VASobs) pain (r = .74) was shown and inter- and intrarater
      reliability coefficients were high (.87 and .89, respectively). Construct
      validity was shown by scale responsiveness to painful stimuli (4.6 times increase
      in scores across phases) and the capacity of the scale to distinguish between
      painful versus nonpainful procedures (P < .001). However, mean baseline scores
      for procedures were not 0 (likely a function of item descriptors for a "0" score)
      and the mean difference increased across phases for children with baseline scores
      >3, which was much lower than for children with scores <3 (P = .0001). Finally,
      28% of scores changed after the second viewing of a video segment. The MBPS
      appears reliable and sensitive to procedural pain when applied by clinicians.
      Results question the capacity of the scale to differentiate between pain- and
      nonpain-related distress, the feasibility of this scale, and the appropriateness
      of item descriptors for medical procedures. PERSPECTIVE: This article presents
      the psychometric and practical properties of the MBPS applied to assess
      procedural pain. Identification of a suitable scale for this purpose will support
      improved pain management in infants and young children who undergo painful
      procedures.

PMID- 29454048
TI  - New Insights into the Molecular Characteristics of Pulmonary Carcinoids and Large
      Cell Neuroendocrine Carcinomas, and the Impact on Their Clinical Management.
AB  - Carcinoids and large cell neuroendocrine carcinomas (LCNECs) are rare
      neuroendocrine lung tumors. Here we provide an overview of the most updated data
      on the molecular characteristics of these diseases. Recent genomic studies showed
      that carcinoids generally contain a low mutational burden and few recurrently
      mutated genes. Most of the reported mutations occur in chromatin-remodeling genes
      (e.g., menin 1 gene [MEN1]), and few affect genes of the phosphoinositide 3
      kinase (PI3K)-AKT-mechanistic target of rapamycin gene pathway. Aggressive
      disease has been related to chromothripsis, DNA-repair gene mutations, loss of
      orthopedia homeobox/CD44, and upregulation of ret proto-oncogene gene (RET) gene
      expression. In the case of LCNECs, which present with a high mutation burden, two
      major molecular subtypes have been identified: one with biallelic inactivation of
      tumor protein p53 gene (TP53) and retinoblastoma gene (RB1), a hallmark of SCLC;
      and the other one with biallelic inactivation of TP53 and serine/threonine kinase
      11 gene (STK11)/kelch like ECH associated protein 1 gene (KEAP1), genes that are
      frequently mutated in NSCLC. These data, together with the identification of
      common mutations in the different components of combined LCNEC tumors, provide
      further evidence of the close molecular relation of LCNEC with other lung tumor
      types. In terms of therapeutic options, future studies should explore the
      association between mechanistic target of rapamycin pathway mutations and
      response to mechanistic target of rapamycin inhibitors in carcinoids. For LCNEC,
      preliminary data suggest that the two molecular subtypes might have a predictive
      value for chemotherapy response, but this observation needs to be validated in
      randomized prospective clinical trials. Finally, delta like Notch canonical
      ligand 3 inhibitors and immunotherapy may provide alternative options for patient
      tailored therapy in LCNEC.

PMID- 29454047
TI  - Renal perivascular adipose tissue: Form and function.
AB  - Renal sympathetic activity affects blood pressure in part by increasing
      renovascular resistance via release of norepinephrine (NE) from sympathetic
      nerves onto renal arteries. Here we test the idea that adipose tissue adjacent to
      renal blood vessels, i.e. renal perivascular adipose tissue (RPVAT), contains a
      pool of NE which can be released to alter renal vascular function. RPVAT was
      obtained from around the main renal artery/vein of the male Sprague Dawley rats.
      Thoracic aortic PVAT and mesenteric PVAT also were studied as brown-like and
      white fat comparators respectively. RPVAT was identified as a mix of white and
      brown adipocytes, because of expression of both brown-like (e.g. uncoupling
      protein 1) and white adipogenic genes. All PVATs contained NE (ng/g tissue,
      RPVAT:524 +/- 68, TAPVAT:740 +/- 16, MPVAT:96 +/- 24). NE was visualized
      specifically in RPVAT adipocytes by immunohistochemistry. The presence of RPVAT
      (+RPVAT) did not alter the response of isolated renal arteries to NE compared to
      responses of arteries without RPVAT (-RPVAT). By contrast, the maximum
      contraction to the sympathomimetic tyramine was ~2* greater in the renal artery
      +PVAT versus -PVAT. Tyramine-induced contraction in +RPVAT renal arteries was
      reduced by the alpha1-adrenoceptor antagonist prazosin and the NE transporter
      inhibitor nisoxetine. These results suggest that tyramine caused release of NE
      from RPVAT. Renal denervation significantly (>50%) reduced NE content of RPVAT
      but did not modify tyramine-induced contraction of +RPVAT renal arteries.
      Collectively, these data support the existence of a releasable pool of NE in
      RPVAT that is independent of renal sympathetic innervation and has the potential
      to change renal arterial function.

PMID- 29454049
TI  - Emergence of vancomycin-intermediate and -resistant Staphylococcus aureus among
      methicillin-resistant S. aureus isolated from clinical specimens in the northwest
      of Iran.
AB  - OBJECTIVES: The aim of this study was to evaluate the frequency as well as the
      phenotypic and molecular characteristics of methicillin-resistant Staphylococcus
      aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) isolates from clinical
      specimens at three university teaching hospitals in Urmia, Northwest Iran, from
      2012-2015. METHODS: Following identification of the isolates, antibiotic
      susceptibility testing was performed. The presence of the mecA, vanA and pvl
      genes was evaluated, and staphylococcal cassette chromosome mec (SCCmec) typing
      was performed. RESULTS: A total of 177 S. aureus isolates were collected from
      various clinical specimens. Antibiotic susceptibility testing revealed high
      resistance rates to penicillin (98.9%), followed by erythromycin (61.6%). A total
      of 95 isolates (53.7%) were confirmed as MRSA. Among the initially screened
      vancomycin-intermediate S. aureus (VISA) isolates, one isolate with a minimum
      inhibitory concentration (MIC) of 6MUg/mL harboured the vanA gene. Eleven MRSA
      isolates (11.6%) were also VRSA. A majority (23/95; 24.2%) of MRSA were
      classified as SCCmec type III. Only 6 MRSA isolates (6.3%) harboured the pvl
      gene. CONCLUSIONS: This study highlights the presence of MRSA along with VISA and
      VRSA in our setting. To our knowledge, this is the first report showing that a
      strain can be defined as VISA phenotypically and as VRSA by molecular analysis.
      Such a finding raises major concerns with regard to control measures and reliable
      laboratory tests for screening of resistant strains.

PMID- 29454050
TI  - When travel is a challenge: Travel medicine and the 'dis-abled' traveller.
AB  - Travellers with recognised disabilities or the dis-ability to function as
      required during a trip have been overlooked in the travel medicine literature.
      This paper provides a starting point for further discussion and research into
      this neglected traveller population. In contrast, tourism research has explored
      travel with a disability for some time in order to understand the travellers'
      needs and to improve services accordingly. The contemporary bio-psycho-social
      understanding of disability serves as the framework for exploring motivations to
      travel as well as barriers, such as inter and intrapersonal, economic, structural
      and attitudinal obstacles. The demands of complex travel planning are
      acknowledged. Attention is also drawn to the particular issue of acquired
      disability. The theoretical discussion is complemented by travellers' own
      accounts using as examples mobility impairment on aeroplanes, sensory
      impairments, and obesity. These insights should inform high quality travel health
      care starting with an exploration of the health professionals' own views on such
      endeavours. Important are appropriate communication skills, an understanding of
      the travellers'/carers' views, wishes and judgment of abilities, as well as the
      appreciation of the reason for the trip, destination and planned activities.
      Challenging may be the need to accept that the traveller/carer will be more
      knowledgeable about the disability, needs, potential problems and solutions than
      the health professional. Finally, medical requirements for destination and
      activity need to be combined with the medical requirements for the dis-abling
      condition. Scarce literature and increasing numbers of travellers with
      disabilities should make this field a research priority in travel medicine.
      Unless there is an absolute medical contraindication, travel health professionals
      should encourage and support travellers for whom travel is a challenge.

PMID- 29454051
TI  - Retrospective observational study of the use of artemether-lumefantrine in the
      treatment of malaria in Japan.
AB  - BACKGROUND: The Research Group on Chemotherapy of Tropical Diseases, Japan,
      introduced artemether-lumefantrine (AL) in late 2002, mainly for treating
      uncomplicated Plasmodium falciparum malaria. Because AL was on the market in
      Japan in March 2017, the effectiveness and safety of AL were analyzed to help
      medical personnel use AL optimally. METHODS: Case report forms submitted by the
      attending physicians were analyzed. When necessary, direct contact with the
      attending physicians was made to obtain detailed information. RESULTS:
      Effectiveness analysis was performed for 62 cases and safety analysis was
      performed for 66 cases. In P. falciparum malaria, the overall cure rate was 91.1%
      (51/56), of which the cure rates for Japanese and non-Japanese patients were
      82.1% (23/28) and 100% (28/28), respectively. The successfully treated cases
      included severe P. falciparum malaria, with parasite densities exceeding
      500,000/MUL. Adverse events were reported in 14 patients, including delayed
      hemolytic anemia which occurred in the top four highest parasitemic cases.
      CONCLUSIONS: AL treatment failure in P. falciparum malaria may not be rare among
      non-immune individuals, including Japanese. The possibility of delayed hemolytic
      anemia, which occurs preferentially in high parasitemic cases, should be
      considered following AL treatment.

PMID- 29454052
TI  - Activity of nitric oxide synthase isoforms in acute brain oxidative damage
      induced by ozone exposure.

PMID- 29454053
TI  - Development and characterization of nano biopolymer containing cumin oil as a new
      approach to enhance antioxidant properties of button mushroom.
AB  - The aim of present study was to design a controlled release system using Cuminum
      cyminum essential oil loaded chitosan nanoparticles (CEO-CSNPs) and evaluate its
      effect on catalase (CAT), glutathione reductase (GR), peroxidase (POD) activity
      and ascorbic acid content of Agaricus bisporus fruit bodies during 20days of
      storage at 4 degrees C. The success of encapsulation was evaluated through TEM,
      DLS, FT-IR and spectrophotometry and its release behavior was studied in buffer
      solutions with different pH. The CEO-CSNPs exhibited an average size of 30 to
      80nm with a spherical shape. Encapsulation efficiency (EE) and loading capacity
      (LC) were 4.46 to 17.89% and 2.47 to 6.68%, respectively. The highest CAT and GR
      activity was observed in samples packed with CEO-CSNPs after 15days of storage.
      In contrast, POD activity reached a peak at the end of storage in control
      samples. Interestingly, after 20days the level of POD increased 17.13% in CEO
      CSNPs treatment, as compared with the initial level of the mentioned enzyme. At
      the end of storage, ascorbic acid content in samples treated with CEO-CSNPs was
      significantly higher than that detected in the control samples. In brief,
      application of CEO loaded chitosan nanoparticles in packages effectively
      increased the antioxidant activity in white button mushroom and showed promising
      results for extending the shelf life of treated samples.

PMID- 29454054
TI  - Genomic perspectives of spider silk genes through target capture sequencing:
      Conservation of stabilization mechanisms and homology-based structural models of
      spidroin terminal regions.
AB  - A powerful system for studying protein aggregation, particularly rapid self
      assembly, is spider silk. Spider silks are proteinaceous and silk proteins are
      synthesized and stored within silk glands as liquid dope. As needed, liquid dope
      is near-instantaneously transformed into solid fibers or viscous adhesives. The
      dominant constituents of silks are spidroins (spider fibroins) and their terminal
      domains are vital for the tight control of silk self-assembly. To better
      understand spidroin termini, we used target capture and deep sequencing to
      identify spidroin gene sequences from six species representing the araneoid
      families of Araneidae, Nephilidae, and Theridiidae. We obtained 145 terminal
      regions, of which 103 are newly annotated here, as well as novel variants within
      nine diverse spidroin types. Our comparative analyses demonstrated the
      conservation of acidic, basic, and cysteine amino acid residues across spidroin
      types that had been proposed to be important for monomer stability, dimer
      formation, and self-assembly from a limited sampling of spidroins. Computational,
      protein homology modeling revealed areas of spidroin terminal regions that are
      highly conserved in three-dimensions despite sequence divergence across spidroin
      types. Analyses of our dense sampling of terminal regions suggest that most
      spidroins share stabilization mechanisms, dimer formation, and tertiary
      structure, despite producing functionally distinct materials.

PMID- 29454055
TI  - Optimization, chain conformation and characterization of exopolysaccharide
      isolated from Leuconostoc mesenteroides DRP105.
AB  - Response surface methodology (RSM) was used to optimize the fermentation
      condition of exopolysaccharide (EPS) producing strain Leuconostoc mesenteroides
      DRP105. Result showed that the optimum condition was sucrose 86.83g/L, tryptone
      15.47g/L, initial pH7.18 and maximum yield was 53.79+/-0.78g/L in 36h
      fermentation. Chain conformation was characterized by Congo red test, beta
      elimination and circular dichroism (CD), which indicated that the EPS was O
      linkage and exhibited random coil structure in aqueous solution. CD results
      concluded hydrogen-bond interaction and chirality might be connected with
      concentration. Purified EPS has a higher degradation temperature of 279.42
      degrees C, suggesting high thermal stability of the EPS. The absolute value of
      zeta potential and particle size were enhanced with increasing concentration.
      Crude EPS and its purified fraction were found to have moderate DPPH, hydroxyl,
      superoxide anion radicals scavenging activities and reducing power. This study
      provided a high yield EPS with unique characteristics for industrial
      applications.

PMID- 29454056
TI  - Biophysical and immunological characterization of 2-dRib modified HSA and its
      implications in diabetes mellitus.
AB  - Glycoxidation of protein may lead to develop diabetes. In the present study,
      different concentrations of 2-deoxy d-ribose (2-dRib) were used to modify human
      serum albumin (HSA). Nitro Blue Tetrazolium (NBT) assay results showed that yield
      of the fructosamine content was directly proportional to the concentration of 2
      dRib. UV and fluorescence spectroscopy results showed an increment in
      hyperchromicity and decrease in fluorescence intensity of 2-dRib modified HSA as
      compared to native HSA. Further secondary structural changes were confirmed by UV
      circular dichroism (UV-CD) and Fourier transform infrared spectroscopy (FT-IR).
      To evaluate the immunogenicity of 2-dRib modified HSA, rabbits were immunized
      with native and 2-dRib modified HSA. Modified HSA sera showed high antibodies
      titre as compared to native HSA. Moreover, the binding affinity of native and
      modified HSA with diabetic patient's sera has been evaluated by direct binding
      ELISA. It was found that diabetic patient's sera showed high binding affinity
      with the modified HSA as compared to native HSA. On the basis of above findings,
      it can be concluded that 2-dRib is a potential glycating agent that can cause
      alteration in HSA structure and make HSA more immunogenic that might play a role
      in onset and progression of diabetes mellitus and its complications.

PMID- 29454057
TI  - Pullulan suppresses the denaturation of myofibrillar protein of grass carp
      (Ctenopharyngodon idella) during frozen storage.
AB  - This study aims to investigate the effect of pullulan on the denaturation of the
      myofibrillar protein of grass carp (Ctenopharyngodon idella) during frozen
      storage at -18 degrees C for 30days. Pullulan or commercial cryoprotectant (1g
      dry weight) were added to 100g of the myofibrillar protein of grass carp (C.
      idella), respectively, which was frozenly stored at -18 degrees C for 30days, and
      the changes in the state of unfrozen of water, solubility, Ca2+
      adenylpyrophosphatase (ATPase) activity, and sulfhydryl content of myofibrils
      were monitored during frozen storage. Pullulan addition increased unfrozen water
      and sulfhydryl contents in the myofibrillar protein and solubility and ATPase
      activity of the myofibrillar protein compared with those of the control during
      frozen storage at -18 degrees C. Moreover, the cryoprotective efficiency of
      pullulan on the myofibrillar protein of grass carp (C. idella) was higher than
      that of commercial cryoprotectant.

PMID- 29454058
TI  - Carboxymethyl konjac glucomannan - crosslinked chitosan sponges for wound
      dressing.
AB  - In this paper, carboxymethyl konjac glucomannan (CMKGM) was obtained by carboxyl
      modification of konjac glucomannan. Then CMKGM and chitosan (CS) were crosslinked
      and freeze-dried to prepare CMKGM/CS composite sponges with different
      proportions. The structure and micromorphology of CMKGM/CS sponges were
      investigated by FTIR spectroscopy and SEM. The SEM results showed that the pore
      structure of the composite sponge gradually increased with the increase of CMKGM
      content. To assess the applicability of CMKGM/CS composite sponges as wound
      dressing, the swelling behavior, water vapor transmission rate (WVTR),
      biocompatibility (cytotoxicity and hemolysis) were analyzed. The results
      indicated that CMKGM/CS composite sponges possessed high swelling ratio, proper
      WVTR and good biocompatibility, which might accelerate tissue regeneration.
      Meanwhile, in vivo experiments demonstrated that CMKGM/CS composite sponges could
      effectively heal full-layer wound of skin defects of male ICR mice.

PMID- 29454059
TI  - Towards a regulatory use of alternative developmental neurotoxicity testing
      (DNT).
AB  - There is a need for a more effective Developmental Neurotoxicity (DNT) screening
      which is scientifically driven by the fact that the developing nervous system
      might be more sensitive to exposures to some hazardous chemical. Additional
      concern comes from the recent societal concerns that toxic chemicals can
      contribute to the prevalence of neurodevelopment disabilities. Consequently,
      hazard identification and actions to reduce exposure to these chemicals is a
      priority in chemical risk assessment. To reach this goal a cost-efficient testing
      strategy based on a reliable in-vitro testing battery should be developed.
      Although this goal is representing a huge challenge in risk assessment, available
      data and methodologies are supporting the ultimate aim of developing a predictive
      model able to respond to different regulatory based problem formulations.

PMID- 29454060
TI  - AOP-DB: A database resource for the exploration of Adverse Outcome Pathways
      through integrated association networks.
AB  - The Adverse Outcome Pathway (AOP) framework describes the progression of a
      toxicity pathway from molecular perturbation to population-level outcome in a
      series of measurable, mechanistic responses. The controlled, computer-readable
      vocabulary that defines an AOP has the ability to, automatically and on a large
      scale, integrate AOP knowledge with publically available sources of biological
      high-throughput data and its derived associations. To support the discovery and
      development of putative (existing) and potential AOPs, we introduce the AOP-DB,
      an exploratory database resource that aggregates association relationships
      between genes and their related chemicals, diseases, pathways, species orthology
      information, ontologies, and gene interactions. These associations are mined from
      publically available annotation databases and are integrated with the AOP
      information centralized in the AOP-Wiki, allowing for the automatic
      characterization of both putative and potential AOPs in the context of multiple
      areas of biological information, referred to here as "biological entities". The
      AOP-DB acts as a hypothesis-generation tool for the expansion of putative AOPs,
      as well as the characterization of potential AOPs, through the creation of
      association networks across these biological entities. Finally, the AOP-DB
      provides a useful interface between the AOP framework and existing chemical
      screening and prioritization efforts by the US Environmental Protection Agency.

PMID- 29454061
TI  - Activation of NLRX1-mediated autophagy accelerates the ototoxic potential of
      cisplatin in auditory cells.
AB  - To date, the mechanism (s) underlying the cisplatin-elicited ototoxicity has not
      been elucidated fully. Nucleotide-binding domain and leucine-rich-repeat
      containing family member *1 (NLRX1), a cytoplasmic pattern recognition receptor,
      is tightly related to mitochondrial function, reactive oxygen species (ROS)
      production, and autophagy. In this work, autophagy alteration, NLRX1 expression,
      ROS generation and cell injury were investigated correspondingly by
      immunofluorescence staining, western-blot, TEM, flow cytometry and MTT in HEI-OC1
      cells of both NLRX1 overexpression and silencing in response to cisplatin
      stimulus. We found that NLRX1 expression was increased concurrent with the
      increase of autophagy activation in HEI-OC1 cells under the cisplatin insult.
      NLRX1 overexpression led to the amount of accumulation of autophagsomes in HEI
      OC1 cells in normal condition and a higher activation of autophagy concurrent
      with cell injury in HEI-OC1 cells treated with cisplatin, whereas, NLRX1
      silencing decreased the activation level of autophagy concurrent with increased
      cell viability in HEI-OC1 cells treated with cisplatin. Mechanistic studies
      showed that NLRX1 potentiated mitochondrial-derived ROS generation in response to
      cisplatin exposure. Inhibition of ROS generation significantly prevented
      autophagy activation and apoptosis both in HEI-OC1cells and cochlear explants
      treated with cisplatin. The findings from this work reveal that NLRX1 sensitizes
      auditory cells in vitro to cisplatin-induced ototoxity via autophagic cell death
      pathway, providing another strategy against cisplatin-induced ototoxity.

PMID- 29454062
TI  - Laser-assisted delivery of synergistic combination chemotherapy in in vivo skin.
AB  - The effectiveness of topical drugs for treatment of non-melanoma skin cancer is
      greatly reduced by insufficient penetration to deep skin layers. Ablative
      fractional lasers (AFLs) are known to enhance topical drug uptake by generating
      narrow microchannels through the skin, but information on AFL-drug delivery in in
      vivo conditions is limited. In this study, we examined pharmacokinetics,
      biodistribution and toxicity of two synergistic chemotherapy agents, cisplatin
      and 5-fluorouracil (5-FU), following AFL-assisted delivery alone or in
      combination in in vivo porcine skin. Detected at 0-120 h using mass spectrometry
      techniques, we demonstrated that fractional CO2 laser pretreatment (196
      microchannels/cm2, 852 MUm ablation depth) leads to rapid drug uptake in 1500 MUm
      deep skin layers, with a sixfold enhancement in peak cisplatin concentrations
      versus non-laser-treated controls (5 h, P = 0.005). Similarly, maximum 5-FU
      deposition was measured within an hour of AFL-delivery, and exceeded peak
      deposition in non-laser-exposed skin that had undergone topical drug exposure for
      5 days. Overall, this accelerated and deeper cutaneous drug uptake resulted in
      significantly increased inflammatory and histopathological effects. Based on
      clinical scores and transepidermal water loss measurement, AFL intensified local
      toxic responses to drugs delivered alone and in combination, while systemic drug
      exposure remained undetectable. Quantitative histopathologic analyses
      correspondingly revealed significantly reduced epidermal proliferation and
      greater cellular apoptosis after AFL-drug delivery; particularly after combined
      cisplatin + 5-FU exposure. In sum, by overcoming the primary limitation of
      topical drug penetration and providing accelerated, enhanced and deeper delivery,
      AFL-assisted combination chemotherapy may represent a promising treatment
      strategy for non-melanoma skin cancer.

PMID- 29454063
TI  - Characterization of nanomedicines: A reflection on a field under construction
      needed for clinical translation success.
AB  - The nanotechnology revolution offers many expectations for the improvement of
      medicine treatments. At present, nanomedicine (NM) development is hampered by
      methodological barriers for a better characterization and a wider understanding
      of their in vivo behavior. While regulatory agencies setup guidelines to support
      NM translation from bench to bedside, the gap is still hardly overcome by main
      nanomedicines. One lever for filling this gap is a better characterization, thus
      increasing the global knowledge about the NM itself but also validate the
      confidence in terms of batch to batch reproducibility of such complex nano
      objects. Here, we review the current methodologies routinely used for clinical
      release of nanomedicine batches in compliance with official guidelines. We
      confront them to the extreme sharpness of biological systems and finally discuss
      future possible orientations for a better characterization of NMs, needed to
      bridge the gap between physicochemical properties and biological fate.

PMID- 29454065
TI  - Impact of food additives on the gut-brain axis.
AB  - The mammalian intestinal tract is heavily colonized with a complex community of
      micro-organisms, present at a very high density, and containing an estimated
      amount of 1014 bacteria. The microbiota generally benefits the host, as it plays
      a central role in maturing the immune system, protecting against infection by
      entero-pathogens such as Clostridium difficile, and favoring nutrient
      digestion/energy extraction in our intestine. An altered microbiota, however, can
      become detrimental and lead to inflammation, metabolic disorders, and even
      altered behavior/neuroinflammation. While there are many factors involved in
      regulating the intestinal microbiota composition and the way it interacts with
      its host, this review will focus on the role played by food additives on
      host/microbiota relationship.

PMID- 29454064
TI  - RNA-based micelles: A novel platform for paclitaxel loading and delivery.
AB  - RNA can serve as powerful building blocks for bottom-up fabrication of
      nanostructures for biotechnological and biomedical applications. In addition to
      current self-assembly strategies utilizing base pairing, motif piling and
      tertiary interactions, we reported for the first time the formation of RNA based
      micellar nanoconstruct with a cholesterol molecule conjugated onto one helical
      end of a branched pRNA three-way junction (3WJ) motif. The resulting amphiphilic
      RNA micelles consist of a hydrophilic RNA head and a covalently linked
      hydrophobic lipid tail that can spontaneously assemble in aqueous solution via
      hydrophobic interaction. Taking advantage of pRNA 3WJ branched structure, the
      assembled RNA micelles are capable of escorting multiple functional modules. As a
      proof of concept for delivery for therapeutics, Paclitaxel was loaded into the
      RNA micelles with significantly improved water solubility. The successful
      construction of the drug loaded RNA micelles was confirmed and characterized by
      agarose gel electrophoresis, atomic force microscopy (AFM), dynamic light
      scattering (DLS), and fluorescence Nile Red encapsulation assay. The estimate
      critical micelle formation concentration ranges from 39 nM to 78 nM. The
      Paclitaxel loaded RNA micelles can internalize into cancer cells and inhibit
      their proliferation. Further studies showed that the Paclitaxel loaded RNA
      micelles induced cancer cell apoptosis in a Caspase-3 dependent manner but RNA
      micelles alone exhibited low cytotoxicity. Finally, the Paclitaxel loaded RNA
      micelles targeted to tumor in vivo without accumulation in healthy tissues and
      organs. There is also no or very low induction of pro-inflammatory response.
      Therefore, multivalence, cancer cell permeability, combined with controllable
      assembly, low or non toxic nature, and tumor targeting are all promising features
      that make our pRNA micelles a suitable platform for potential drug delivery.

PMID- 29454066
TI  - Walking behavior in a circular arena modified by pulsed light stimulation in
      Drosophila melanogaster w1118 line.
AB  - The Drosophila melanogaster white-eyed w1118 line serves as a parental stock,
      allowing genetic recombination of any gene of interest along with a readily
      recognizable marker. w1118 flies display behavioral susceptibility to
      environmental stimulation such as light. It is of great importance to
      characterize the behavioral performance of w1118 flies because this would provide
      a baseline from which the effect of the gene of interest could be differentiated.
      Little work has been performed to characterize the walking behavior in adult
      w1118 flies. Here we show that pulsed light stimulation increased the regularity
      of walking trajectories of w1118 flies in circular arenas. We statistically
      modeled the distribution of distances to center and extracted the walking
      structures of w1118 flies. Pulsed light stimulation redistributed the time
      proportions for individual walking structures. Specifically, pulsed light
      stimulation reduced the episodes of crossing over the central region of the
      arena. An addition of four genomic copies of mini-white, a common marker gene for
      eye color, mimicked the effect of pulsed light stimulation in reducing crossing
      in a circular arena. The reducing effect of mini-white was copy-number-dependent.
      These findings highlight the rhythmic light stimulation-evoked modifications of
      walking behavior in w1118 flies and an unexpected behavioral consequence of mini
      white in transgenic flies carrying w1118 isogenic background.

PMID- 29454067
TI  - Considering our methods: Methodological issues with rodent models of appetite and
      obesity research.
AB  - A large number of animal models are currently used in appetite and obesity
      research. Because the worldwide incidence of obesity continues to climb, it is
      imperative that animal models sharing characteristics of human obesity and its co
      morbidities be used appropriately in the quest for novel preventions or
      treatments. There is probably no animal model, at least in rodents, that
      recapitulates all aspects of "common" human obesity and its comorbidities, but
      rodent models allow insight into specific mechanisms of disease or its
      consequences. Frequently used obesity models can be partitioned into different
      categories, the major ones being a) based on mutations or manipulations of one or
      a few individual genes or b) those in genetically intact animals exposed to
      obesogenic environments such as, e.g., being maintained on high-fat diets or
      being raised in small litters. Characteristics of these models include distinct
      phenotypes of obesity, hyperphagia or changes in energy metabolism, and frequent
      comorbidities of obesity, like hyperglycemia, insulin resistance or diabetes-like
      syndromes. This review which is based on a presentation given during the Annual
      Meeting of the Society for the Study of Ingestive Behavior in July 2017 points
      out some observations and characteristics of rodent models in obesity and
      diabetes research. The choice of rodent models discussed here is subjective and
      based on the author's own experience or on fruitful discussions with colleagues
      about the pros and cons of specific models. Hence, this review, by no means, is
      meant to give a complete picture of rodent models used in this type of research,
      but the review tries to bring up some issues which, in the author's mind, may
      also be relevant for models not discussed here. For example, by discussing
      specific mouse and rat models, similarities and differences between mice and rats
      will be discussed that need to be considered to interpret experimental findings
      cautiously and in the context of the respective animal model. Knowing which
      animal model to use means, knowing its limitations.

PMID- 29454068
TI  - O-GlcNAcylation of RACK1 promotes hepatocellular carcinogenesis.
AB  - BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked beta
      N-acetylglucosaminylation (O-GlcNAcylation) are general features during
      tumorigenesis. Nevertheless, whether and how these two pathways are interlinked
      remain unknown. Our previous study indicated that ribosomal receptor for
      activated C-kinase 1 (RACK1) promoted chemoresistance and growth in
      hepatocellular carcinoma (HCC). The aim of this study is to examine the role of
      RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis. METHODS:
      The site(s) of RACK1 for O-GlcNAcylation was mapped by mass spectrometry
      analysis. HCC cell lines were employed to examine the effects of RACK1 O
      GlcNAcylation on the translation of oncogenic factors and behaviors of tumor
      cells in vitro. Transgenic knock-in mice were used to detect the role of RACK1 O
      GlcNAcylation in modulating HCC tumorigenesis in vivo. The correlation of RACK1 O
      GlcNAcylation with tumor progression and relapse were analyzed in clinical HCC
      samples. RESULTS: We found that ribosomal RACK1 was highly modified by O-GlcNAc
      at Ser122. O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome
      binding and interaction with PKCbetaII (PRKCB), leading to increased eukaryotic
      translation initiation factor 4E phosphorylation and translation of potent
      oncogenes in HCC cells. Genetic ablation of RACK1 O-GlcNAcylation at Ser122
      dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and
      in diethylnitrosamine (DEN)-induced HCC mouse model. Increased RACK1 O
      GlcNAcylation was also observed in HCC patient samples and correlated with tumor
      development and recurrence after chemotherapy. CONCLUSIONS: These findings
      demonstrate that RACK1 acts as key mediator linking O-GlcNAc metabolism to cap
      dependent translation during HCC tumorigenesis. Targeting RACK1 O-GlcNAcylation
      provides promising options for HCC treatment. LAY SUMMARY: O-GlcNAcylation of
      ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes
      its stability, ribosome localization and interaction with the protein kinase,
      PKCbetaII, thus driving the translation of oncogenes and tumorigenesis of
      hepatocellular carcinoma. Increased O-GlcNAcylation of ribosomal receptor for
      activated C-kinase 1 is positively correlated with tumor growth, metastasis and
      recurrence in patients with hepatocellular carcinoma.

PMID- 29454069
TI  - Recipient characteristics and morbidity and mortality after liver
      transplantation.
AB  - BACKGROUND AND AIMS: Over the last decade, liver transplantation of sicker, older
      non-hepatitis C cirrhotics with multiple co-morbidities has increased in the
      United States. We sought to identify an easily applicable set of recipient
      factors among HCV negative adult transplant recipients associated with
      significant morbidity and mortality within five years after liver
      transplantation. METHODS: We collected national (n = 31,829, 2002-2015) and
      center-specific data. Coefficients of relevant recipient factors were converted
      to weighted points and scaled from 0-5. Recipient factors associated with graft
      failure included: ventilator support (five patients; hazard ratio [HR] 1.59; 95%
      CI 1.48-1.72); recipient age >60 years (three patients; HR 1.29; 95% CI 1.23
      1.36); hemodialysis (three patients; HR 1.26; 95% CI 1.16-1.37); diabetes (two
      patients; HR 1.20; 95% CI 1.14-1.27); or serum creatinine >=1.5 mg/dl without
      hemodialysis (two patients; HR 1.15; 95% CI 1.09-1.22). RESULTS: Graft survival
      within five years based on points (any combination) was 77.2% (0-4), 69.1% (5-8)
      and 57.9% (>8). In recipients with >8 points, graft survival was 42% (model for
      end-stage liver disease [MELD] score <25) and 50% (MELD score 25-35) in
      recipients receiving grafts from donors with a donor risk index >1.7. In center
      specific data within the first year, subjects with >=5 points (vs. 0-4) had
      longer hospitalization (11 vs. 8 days, p <0.01), higher admissions for
      rehabilitation (12.3% vs. 2.7%, p <0.01), and higher incidence of cardiac disease
      (14.2% vs. 5.3%, p <0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p
      = 0.03) within five years. CONCLUSION: The impact of co-morbidities in an MELD
      based organ allocation system need to be reassessed. The proposed clinical tool
      may be helpful for center-specific assessment of risk of graft failure in non-HCV
      patients and for discussion regarding relevant morbidity in selected subsets. LAY
      SUMMARY: Over the last decade, liver transplantation of sicker, older patient
      with multiple co-morbidities has increased. In this study, we show that a set of
      recipient factors (recipient age >60 years, ventilator status, diabetes,
      hemodialysis and creatinine >1.5 mg/dl) can help identify patients that may not
      do well after transplant. Transplanting sicker organs in patients with certain
      combinations of these characteristics leads to lower survival.

PMID- 29454070
TI  - Association of polymorphic variants of IL-1beta and IL-1RN genes in the
      development of Graves' disease in Kashmiri population (North India).
AB  - PURPOSE: Graves' disease (GD) is a multigenic, organ specific autoimmune disorder
      with a strong genetic predisposition and IL-1beta has been shown to be involved
      in its pathogenesis. The present study was aimed to determine the genetic
      associations between polymorphisms of IL-1beta gene promoter region (-511 T>C)
      (rs16944), exon 5 (+3954 C>T) (rs1143634) and IL-1RN gene VNTR (rs2234663)
      polymorphism in patients with GD in ethnic Kashmiri population. METHODS: A total
      of 135 Graves' disease patients and 150 healthy individuals were included in the
      study. PCR and PCR-based restriction analysis methods were done for IL-1RNVNTR
      and IL-1beta gene polymorphisms respectively. RESULTS: We found statistically
      significant increased frequencies of the C/C + CT genotype (P = 0.001; odds ratio
      (OR) = 5.04, 95% confidence interval (CI) = 3.02-8.42) and the C allele (P =
      0.001; OR = 3.10, 95% CI = 2.14-4.50) in IL-1beta gene promoter polymorphism
      (rs16944) with GD patients compared to normal controls. Also in the exon 5
      (rs1143634), a significant increase in frequency of the C/C homozygous genotype
      (P = 0.001; OR = 0.18, 95% CI = 0.11-0.30) and C allele (P = 0.001; OR = 0.31,
      95% CI = 0.20-0.48) was observed in GD cases as against controls. For IL-1RNVNTR
      (rs2234663), we didn't observe any significant difference in the allelic and
      genotypic frequencies between cases and controls. CONCLUSION: Our findings
      suggest that both promoter and exon polymorphisms of IL-1beta gene have a
      significant role in the risk of developing GD, whereas IL-1RNVNTR has no
      association with GD.

PMID- 29454071
TI  - HLA in North Colombia Chimila Amerindians.
AB  - HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from
      Sabana de San Angel (North Colombian Coast) by using high resolution molecular
      typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02
      BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos
      Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had
      already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru
      (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern
      according to HLA allele or haplotype frequencies is lacking in Amerindians, as
      already known. Also, five new extended haplotypes were found in Chimila
      Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with
      aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in
      New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia.
      Finally, this study may show a model of evolutionary factors acting and rising
      one HLA allele frequency (-A*24:02), but not in others that belong to the same or
      different HLA loci.

PMID- 29454072
TI  - Killer cell immunoglobulin-like receptor genotypes in the Turkish population.
AB  - One hundred eighty-seven healthy and unrelated volunteers from various regions of
      Turkey were selected for the study. Killer-cell immunoglobulin-like receptors
      (KIR) genotyping was performed by polymerase chain reaction using commercial
      sequence-specific oligonucleotide probe (SSOP) kits. Gene frequencies of the
      Turkish population were determined by direct counting of the positive and
      negative loci. The genotype data is publicly available in the Allele Frequencies
      Net Database under the population name "Turkey KIR pop 3" number "3399".

PMID- 29454073
TI  - The accumulation of assembly intermediates of the mitochondrial complex I matrix
      arm is reduced by limiting glucose uptake in a neuronal-like model of MELAS
      syndrome.
AB  - Ketogenic diet (KD) which combined carbohydrate restriction and the addition of
      ketone bodies has emerged as an alternative metabolic intervention used as an
      anticonvulsant therapy or to treat different types of neurological or
      mitochondrial disorders including MELAS syndrome. MELAS syndrome is a severe
      mitochondrial disease mainly due to the m.3243A > G mitochondrial DNA mutation.
      The broad success of KD is due to multiple beneficial mechanisms with distinct
      effects of very low carbohydrates and ketones. To evaluate the metabolic part of
      carbohydrate restriction, transmitochondrial neuronal-like cybrid cells carrying
      the m.3243A > G mutation, shown to be associated with a severe complex I
      deficiency was exposed during 3 weeks to glucose restriction. Mitochondrial
      enzyme defects were combined with an accumulation of complex I (CI) matrix
      intermediates in the untreated mutant cells, leading to a drastic reduction in CI
      driven respiration. The severe reduction of CI was also paralleled in post-mortem
      brain tissue of a MELAS patient carrying high mutant load. Importantly, lowering
      significantly glucose concentration in cell culture improved CI assembly with a
      significant reduction of matrix assembly intermediates and respiration capacities
      were restored in a sequential manner. In addition, OXPHOS protein expression and
      mitochondrial DNA copy number were significantly increased in mutant cells
      exposed to glucose restriction. The accumulation of CI matrix intermediates
      appeared as a hallmark of MELAS pathophysiology highlighting a critical
      pathophysiological mechanism involving CI disassembly, which can be alleviated by
      lowering glucose fuelling and the induction of mitochondrial biogenesis,
      emphasizing the usefulness of metabolic interventions in MELAS syndrome.

PMID- 29454075
TI  - The G protein-coupled P2Y6 receptor promotes colorectal cancer tumorigenesis by
      inhibiting apoptosis.
AB  - Colorectal tumors are immersed in an array of tumor-promoting factors including
      extracellular nucleotides such as uridine 5'-diphosphate (UDP). UDP is the
      endogenous agonist of the G protein-coupled P2Y6 receptor (P2Y6R), which may
      contribute to the formation of a tumor-promoting microenvironment by coordinating
      resistance to apoptosis. Colorectal cancer (CRC) was chemically induced in P2ry6
      knockout (P2ry6-/-) mice using azoxymethane and dextran sulfate sodium
      challenges. Mice were euthanatized and their tumor load determined. Fixed tissues
      were stained for histological and immunohistochemistry analysis. Tumoroids were
      also prepared from CRC tumors resected from P2ry6+/+ mice to determine the role
      of P2Y6R in resistance to apoptosis, whereas HT29 carcinoma cells were used to
      elucidate the signaling mechanism involved in P2Y6R anti-apoptotic effect. P2ry6
      /- mice developed a reduced number of colorectal tumors with apparent tumors
      having smaller volumes. Overall dysplastic score was significantly lower in P2ry6
      /- animals. Stimulation of P2Y6R with the selective agonist MRS2693 protected HT
      29 cells from TNFalpha-induced apoptosis. This protective effect was mediated by
      the stabilizing phosphorylation of the X-linked inhibitor of apoptosis protein
      (XIAP) by AKT. Using CRC-derived tumoroids, P2Y6R activation was found to
      contribute to chemoresistance since addition of the P2Y6R agonist MRS2693
      significantly prevented the cytotoxic effect of 5-fluorouracil. The present study
      shows that sustained activation of P2Y6R may contribute to intestinal
      tumorigenesis by blocking the apoptotic process and by contributing to
      chemoresistance, a substantial concern in the treatment of patients with CRC.
      These results suggest that P2Y6R may represent a prime target for reducing
      colorectal carcinogenesis.

PMID- 29454076
TI  - The biological basis of treating jaw discrepancies: An interplay of mechanical
      forces and skeletal configuration.
AB  - Jaw discrepancies and malrelations affect a large proportion of the general
      population and their treatment is of utmost significance for individuals' health
      and quality of life. The aim of their therapy is the modification of aberrant jaw
      development mainly by targeting the growth potential of the mandibular condyle
      through its cartilage, and the architectural shape of alveolar bone through a
      suture type of structure, the periodontal ligament. This targeted treatment is
      achieved via external mechanical force application by using a wide variety of
      intraoral and extraoral appliances. Condylar cartilage and sutures exhibit a
      remarkable plasticity due to the mechano-responsiveness of the chondrocytes and
      the multipotent mesenchymal cells of the sutures. The tissues respond
      biologically and adapt to mechanical force application by a variety of signaling
      pathways and a final interplay between the proliferative activity and the
      differentiation status of the cells involved. These targeted therapeutic
      functional alterations within temporo-mandibular joint ultimately result in the
      enhancement or restriction of mandibular growth, while within the periodontal
      ligament lead to bone remodeling and change of its architectural structure.
      Depending on the form of the malrelation presented, the above treatment
      approaches, in conjunction or separately, lead to the total correction of jaw
      discrepancies and the achievement of facial harmony and function. Overall, the
      treatment of craniofacial and jaw anomalies can be seen as an interplay of
      mechanical forces and adaptations occurring within temporo-mandibular joint and
      alveolar bone. The aim of the present review is to present up-to-date knowledge
      on the mechano-biology behind jaw growth modification and alveolar bone
      remodeling. Furthermore, future molecular targeted therapeutic strategies are
      discussed aiming at the improvement of mechanically-driven chondrogenesis and
      osteogenesis.

PMID- 29454077
TI  - A prospective investigation of neighborhood socioeconomic deprivation and
      physical activity and sedentary behavior in older adults.
AB  - Neighborhood conditions may have an important impact on physical activity and
      sedentary behaviors in the older population. Most previous studies in this area
      are cross-sectional and report mixed findings regarding the effects of
      neighborhood environment on different types of physical activity. Moreover,
      little is known about the prospective relationship between neighborhood
      environment and sedentary behaviors. Our analysis included 136,526 participants
      from the NIH-AARP Diet and Health Study (age 51-70). Neighborhood socioeconomic
      deprivation was measured with an index based on census variables and developed
      using principal component analysis. Physical activity and sedentary behaviors
      were measured both at baseline (1995-1996) and follow-up (2004-2006). Multiple
      regression analyses were conducted to examine the prospective relationship
      between neighborhood deprivation and exercise, non-exercise physical activity,
      and sedentary behaviors, adjusting for baseline physical activity and sedentary
      behaviors as well as potential confounders. We found that more severe
      neighborhood socioeconomic deprivation was prospectively associated with reduced
      time for exercise (beta Q5 vs Q1 (95% confidence interval), hour, -0.85 (-0.95, 
      0.75)) but increased time spent in non-exercise physical activities (1.16 (0.97,
      1.34)), such as household activities, outdoor chores, and walking for
      transportation. Moreover, people from more deprived neighborhoods were also more
      likely to engage in prolonged (>=5 h/day) TV viewing (Odds ratio Q5 vs Q1 (95%
      confidence interval), 1.21 (1.15, 1.27)). In conclusion, neighborhood
      socioeconomic deprivation is associated with physical activity and sedentary
      behavior in the older population. These associations may differ for different
      types of physical activities.

PMID- 29454074
TI  - Nutraceuticals as therapeutic agents for atherosclerosis.
AB  - Atherosclerosis, a chronic inflammatory disorder of medium and large arteries and
      an underlying cause of cardiovascular disease (CVD), is responsible for a third
      of all global deaths. Current treatments for CVD, such as optimized statin
      therapy, are associated with considerable residual risk and several side effects
      in some patients. The outcome of research on the identification of alternative
      pharmaceutical agents for the treatment of CVD has been relatively disappointing
      with many promising leads failing at the clinical level. Nutraceuticals, products
      from food sources with health benefits beyond their nutritional value, represent
      promising agents in the prevention of CVD or as an add-on therapy with current
      treatments. This review will highlight the potential of several nutraceuticals,
      including polyunsaturated fatty acids, flavonoids and other polyphenols, as anti
      CVD therapies based on clinical and pre-clinical mechanism-based studies.

PMID- 29454078
TI  - Looking for capacities rather than vulnerabilities: The moderating effect of
      health assets on the associations between adverse social position and health.
AB  - To increase capacities and control over health, it is necessary to foster assets
      (i.e. factors enhancing abilities of individuals or communities). Acting as a
      buffer, assets build foundations for overcoming adverse conditions and improving
      health. However, little is known about the distribution of assets and their
      associations with social position and health. In this study, we documented the
      distribution of health assets and examined whether these assets moderate
      associations between adverse social position and self-reported health. A
      representative population-based cross-sectional survey of adults in the Eastern
      Townships, Quebec, Canada (n = 8737) was conducted in 2014. Measures included
      assets (i.e. resilience, sense of community belonging, positive mental health,
      social participation), self-reported health (i.e. perceived health, psychological
      distress), and indicators of social position. Distribution of assets was studied
      in relation to gender and social position. Logistic regressions examined whether
      each asset moderated associations between adverse social position and self
      reported health. Different distributions of assets were observed with different
      social positions. Women were more likely to participate in social activities
      while men were more resilient. Resilience and social participation were
      moderators of associations between adverse social position (i.e. living alone,
      lower household income) and self-reported health. Having assets contributes to
      better health by increasing capacities. Interventions that foster assets and
      complement current public health services are needed, especially for people in
      unfavorable situations. Health and social services decision-makers and
      practitioners could use these findings to increase capacities and resources
      rather than focusing primarily on preventing diseases and reducing risk factors.

PMID- 29454079
TI  - A novel metric that quantifies risk stratification for evaluating diagnostic
      tests: The example of evaluating cervical-cancer screening tests across
      populations.
AB  - Our work involves assessing whether new biomarkers might be useful for cervical
      cancer screening across populations with different disease prevalences and
      biomarker distributions. When comparing across populations, we show that standard
      diagnostic accuracy statistics (predictive values, risk-differences, Youden's
      index and Area Under the Curve (AUC)) can easily be misinterpreted. We introduce
      an intuitively simple statistic for a 2 * 2 table, Mean Risk Stratification
      (MRS): the average change in risk (pre-test vs. post-test) revealed for tested
      individuals. High MRS implies better risk separation achieved by testing. MRS has
      3 key advantages for comparing test performance across populations with different
      disease prevalences and biomarker distributions. First, MRS demonstrates that
      conventional predictive values and the risk-difference do not measure risk
      stratification because they do not account for test-positivity rates. Second,
      Youden's index and AUC measure only multiplicative relative gains in risk
      stratification: AUC = 0.6 achieves only 20% of maximum risk-stratification (AUC =
      0.9 achieves 80%). Third, large relative gains in risk-stratification might not
      imply large absolute gains if disease is rare, demonstrating a "high-bar" to
      justify population-based screening for rare diseases such as cancer. We
      illustrate MRS by our experience comparing the performance of cervical-cancer
      screening tests in China vs. the USA. The test with the worst AUC = 0.72 in China
      (visual inspection with acetic acid) provides twice the risk-stratification (i.e.
      MRS) of the test with best AUC = 0.83 in the USA (human papillomavirus and Pap
      cotesting) because China has three times more cervical precancer/cancer. MRS
      could be routinely calculated to better understand the clinical/public-health
      implications of standard diagnostic accuracy statistics.

PMID- 29454081
TI  - Do preventive medicine physicians practice medicine?
AB  - As some preventive medicine physicians have been denied medical licenses for not
      engaging in direct patient care, this paper attempts to answer the question, "Do
      preventive medicine physicians practice medicine?" by exploring the requirements
      of licensure, the definition of "practice" in the context of modern medicine, and
      by comparing the specialty of preventive medicine to other specialties which
      should invite similar scrutiny. The authors could find no explicit licensure
      requirement for either a certain amount of time in patient care or a number of
      patients seen. No physicians board certified in Public Health and General
      Preventive Medicine sit on any state medical boards. The authors propose that
      state medical boards accept a broad standard of medical practice, which includes
      the practice of preventive medicine specialists, for licensing purposes.

PMID- 29454080
TI  - Is the childhood home food environment a confounder of the association between
      child maltreatment exposure and adult body mass index?
AB  - Childhood maltreatment is consistently associated with adult obesity, leading to
      calls for tailored weight interventions for people with maltreatment histories.
      However, it is possible that the maltreatment-obesity association is spurious and
      driven by unmeasured confounding, in which case such interventions would be
      misplaced. The home food environment in childhood is a potential confounder, but
      its role in the association of maltreatment with obesity has not been examined.
      We used a longitudinal dataset (Project EAT) to examine the association of adult
      retrospective reports of maltreatment history in childhood (1+ types of
      maltreatment before age 18 years) with previously-collected prospective childhood
      reports of home food environment characteristics (availability of healthy foods,
      availability of sweet/salty snack food, family meal frequency, and food
      insufficiency). We then estimated the association between maltreatment and adult
      body mass index (BMI, kg/m2) with and without adjustment for these home food
      environment factors. After adjustment for sociodemographics, maltreatment had a
      0.84 kg/m2 (95% CI: 0.28, 1.41) higher BMI at age 24-39 years, compared to those
      with no maltreatment, after adjustment for sociodemographics, parenting style,
      and BMI in childhood. Additional adjustment for home food environment factors had
      little effect on this association (beta = 0.78 kg/m2; 95% CI: 0.21,1.35),
      suggesting limited confounding influence of the home food environment factors.
      Findings provide additional robust evidence that childhood maltreatment is a risk
      factor for obesity that may warrant tailored interventions.

PMID- 29454082
TI  - A straightforward STED-background corrected fitting model for unbiased STED-FCS
      analyses.
AB  - Combining stimulated emission depletion and fluorescence correlation spectroscopy
      (STED-FCS) provides a powerful and sensitive tool for studying the molecular
      dynamics in live cells with high spatio-temporal resolution. STED-FCS gives
      access to molecular diffusion characteristic at the nanoscale occurring within
      short period of times. However due to the incomplete suppression of fluorescence
      in the STED process, the STED-FCS point spread function (PSF) deviates from a
      Gaussian shape and challenges the analysis of the auto-correlation curves
      obtained by FCS. Here, we model the effect of the incomplete fluorescence
      suppression in STED-FCS experiments and propose a new fitting model improving the
      accuracy of the diffusion times and average molecule numbers measurements. The
      implementation of a STED module with pulsed laser source on a commercial
      confocal/FCS microscope allowed us to apply the STED-background corrected model
      to fit the STED-FCS measurements. The experimental results are in good accordance
      with the theoretical analysis both for the number of molecules and the diffusion
      time which decrease accordingly with the STED power.

PMID- 29454083
TI  - Incidence of Acute Suppurative Sialadenitis in End-Stage Cancer Patients: A
      Retrospective Observational Study.
AB  - CONTEXT: Acute suppurative sialadenitis (hereafter referred to as sialadenitis)
      is accompanied by pain and fever and can diminish the quality of life in end
      stage cancer patients; however, its incidence is not clear. OBJECTIVES: We
      conducted this study to elucidate the incidence of sialadenitis in end-stage
      cancer patients. METHODS: Retrospective review and observational study based on
      patients' medical records. SUBJECTS: About 726 consecutive cancer patients who
      died on the palliative care unit of our hospital between April 2012 and November
      2016 were included. MEASUREMENTS: Median duration between sialadenitis onset and
      death, concomitant treatment, average infusion volume per day, site of onset,
      symptoms, effectiveness of antibiotic treatment, and mean duration until
      symptomatic relief. RESULTS: The incidence of sialadenitis was 2.9% (21 of 726
      cases). The median duration from onset to death was 20 days (range 2-112);
      concomitant treatment included opioids in 11 patients (55%), anticholinergic
      drugs in six patients (28%), steroids in three patients (14%), and oxygen
      inhalation in five patients (23%); average infusion volume per day was 588 +/-
      307 mL; site of onset was submandibular gland in 12 patients (57%) and parotid
      gland in nine patients (42%); and symptoms were pain in 18 patients (85%) and
      fever in 13 patients (61%). Antibiotic treatment was administered in 18 patients
      (85%), and the mean duration until symptomatic relief was 4.0 +/- 1.5 days.
      CONCLUSION: Sialadenitis is a rare complication in end-stage cancer patients;
      however, it is important to recognize that it can be associated with severe
      symptoms, including fever and pain.

PMID- 29454084
TI  - Augmented voluntary consumption of ethanol induced by reward downshift increases
      locomotor activity of male Wistar rats in the elevated plus maze.
AB  - Rats exposed to unexpected reward loss increase voluntary oral consumption of
      ethanol. Such consumption has been assumed to attenuate loss-induced negative
      affect (called emotional self-medication). To test this assumption, food-deprived
      male Wistar rats were exposed to 10 sessions of access to 32% sucrose followed by
      5 sessions of access to 4% sucrose (reward downshift). A two-bottle preference
      test was initiated immediately after each consummatory session to assess ethanol
      intake. The experimental group received access to 2% ethanol and water, whereas
      the control group received access to two water bottles. On sessions 11, 12, and
      15, immediately after the preference test, animals were tested in the elevated
      plus maze (EPM) for signs of anxiety. Sucrose consumption was reduced after the
      32-to-4% sucrose downshift on sessions 11 and 12, but behavior recovered by
      session 15. Consummatory suppression was followed by increased ethanol intake in
      the preference test after sessions 11 and 12, but intake was reduced to preshift
      levels by session 15; no changes were observed in water controls. Finally,
      general activity (closed-arm entries and total arm entries) in the EPM increased
      in the ethanol group on session 12, but not on session 15, relative to water
      controls. The increase in ethanol consumption induced by reward downshift had
      measurable effects on activity as assessed in the EPM. These results show that
      voluntary oral 2% ethanol consumption after reward downshift can affect
      subsequent behavior, but fall short of providing unambiguous evidence that such
      ethanol consumption reduces negative affect.

PMID- 29454085
TI  - Effects of orientation and differential reinforcement II: transitivity and
      transfer across five-member sets.
AB  - A recent report by Amd et al. (2017) demonstrated that orienting towards
      successively presented stimulus-stimulus pairs yielded significantly more
      transitive relations then when those same pairs were differentially reinforced
      following training for three, 3-member stimulus sets. We build on that work in
      four important ways. First, transitivity yields produced by Pavlovian and
      instrumental procedures were compared following training for three 5-member sets
      (A1-B1-C1-D1-E1, A2-B2-C2-D2-E2, A3-B3-C3-D3-E3), where the 'A' stimuli were
      emotional faces and all remaining stimuli were nonsense words. Second, our
      instrumental task here required two orienting/observing responses per trial.
      Third, we compared differences in multi-nodal transfer following Pavlovian and
      instrumental relational learning procedures. Finally, we tested whether
      functioning as 'end terms' in a relational series can mitigate transfer following
      instrumental conditioning. Transitivity, as measured by sorting tests, was
      significantly more pronounced following Pavlovian training. Transfer, assessed
      before and after relational training with two visual analog scales corresponding
      to valence and arousal dimensions, appeared marginally more robust observed for
      participants exposed to the Pavlovian condition. Transfer magnitude was
      positively related with demonstrations of transitivity, regardless of type of
      conditioning.

PMID- 29454086
TI  - High prevalence of factor V Leiden and prothrombin G20101A mutations in Kashmiri
      patients with venous thromboembolism.
AB  - AIM: The genetic variants of the factor V (G1691A), prothrombin (G20210A) and
      MTHFR (C677T) genes have been widely implicated as inherited risk factors for
      developing venous thrombosis. This study was undertaken to reveal the frequency
      of these mutations in Kashmiri patients with venous thromboembolism. METHODOLOGY:
      A case-control study was designed with 250 VTE patients and 250 healthy controls.
      The mutations were analysed using ARMS-PCR and PCR-RFLP approach. RESULT: The
      factor V Leiden G1691A mutation was found in 17/250 (6.8%) VTE patients and
      prothrombin G20210A mutation was found in 7/250 (2.8%) VTE patients while no
      mutation was found in any of the healthy controls. Both the mutations were found
      to be significantly associated with the increased risk of VTE (p = 0.0001 and
      0.0150 respectively) while no association of VTE risk with MTHFR C677T
      polymorphism was found (p = 0.53). CONCLUSION: The increased frequency of factor
      V Leiden G1691A and prothrombin G20210A mutation in VTE patients indicates a
      significant role of these mutations in the development of VTE in our population.
      We therefore suggest the routine screening of these two mutations as
      thrombophilic markers in Kashmiri patients with venous thromboembolism.

PMID- 29454087
TI  - Multi-step splicing of sphingomyelin synthase linear and circular RNAs.
AB  - The SGMS1 gene encodes the enzyme sphingomyelin synthase 1 (SMS1), which is
      involved in the regulation of lipid metabolism, apoptosis, intracellular
      vesicular transport and other significant processes. The SGMS1 gene is located on
      chromosome 10 and has a size of 320 kb. Previously, we showed that dozens of
      alternative transcripts of the SGMS1 gene are present in various human tissues.
      In addition to mRNAs that provide synthesis of the SMS1 protein, this gene
      participates in the synthesis of non-coding transcripts, including circular RNAs
      (circRNAs), which include exons of the 5'-untranslated region (5'-UTR) and are
      highly represented in the brain. In this study, using the high-throughput
      technology RNA-CaptureSeq, many new SGMS1 transcripts were identified, including
      both intronic unspliced RNAs (premature RNAs) and RNAs formed via alternative
      splicing. Recursive exons (RS-exons) that can participate in the multi-step
      splicing of long introns of the gene were also identified. These exons
      participate in the formation of circRNAs. Thus, multi-step splicing may provide a
      variety of linear and circular RNAs of eukaryotic genes in tissues.

PMID- 29454088
TI  - HSF4 transcriptional regulates HMOX-1 expression in HLECs.
AB  - The major causes for cataract formation are free radicals, which are neutralized
      by the endogenous antioxidants. However, how the human lens clean these harmful
      free radicals is still unclear. Transcriptional factor heat shock factor 4 (HSF4)
      is a cataract-causing gene and plays important roles during lens development.
      Here we show that HMOX-1, an anti-oxidase, is a bona fide transcriptional target
      gene of HSF4 in HLECs (human lens epithelial cells). HSF4 directly binds to the
      HSE element in HMOX-1 promoter to mediate its mRNA transcription and protein
      accumulation. The HSE element located at the region of -389 bp to -362 bp
      upstream from the TSS (transcription start site), which is critical for HMOX-1
      transcriptional activation. Furthermore, knockdown of HSF4 by siRNA inhibited
      HMOX-1 expression. Thus, these data revealed a novel transcription target of HSF4
      and provided new insights into anti-oxidation regulation in lens and age-related
      cataract.

PMID- 29454089
TI  - Genome-wide gene expression analysis of 45 days pregnant fetal cotyledons vis-a
      vis non-pregnant caruncles in buffalo (Bubalus bubalis).
AB  - The crosstalk between fetus and mother starts with the onset of placental
      attachment to the uterus. The cotyledons and caruncles are the two anatomically
      distinct structures that play a crucial role in this physiological communication.
      Using Agilent Gene Chip Genome microarray, we measured the expression profile of
      pregnancy cotyledons in comparison to caruncular reminiscence of the uteri in non
      pregnant buffalo (Bubalus bubalis) for the detection of the early post-pregnancy
      rapid changes in cellular expression of mRNA transcripts. We identified a total
      of 497 up- and 578 down-regulated genes with <0.05 the FDR corrected p-values
      using 4 replicates in each group (cotyledons and caruncles) and their role in
      pregnancy. Deep bioinformatics analysis of data revealed the cluster of genes
      involved at the placentome level for various functions such as fetus attachment,
      transport of nutrition, and immune response. Importantly, the pathways like
      Hedgehog/Calcium/Wnt signalling, cell cycle regulation and immune responses
      regulatory functions were highly enriched by the differentially identified genes.
      A very highly up-regulated IL-2 specific gene showed the role of interleukin-2
      signalling in the attachment of the embryo. It was observed that the genes
      responsible for immune response were downregulated, suggesting an immune
      suppressive environment which is required to adopt the semiallogeneic fetus for a
      successful pregnancy. To further evaluate and validate the data, we have
      performed qRT-PCR analysis of twenty-one genes. The present study highlights the
      repertoire of active transcripts in the junction of cotyledons and caruncles,
      which are essential for a successful onset and completion of pregnancy.

PMID- 29454090
TI  - Characterization of vasa homolog in a neotropical catfish, Jundia (Rhamdia
      quelen): Molecular cloning and expression analysis during embryonic and larval
      development.
AB  - We have characterized the full-length vasa cDNA from Jundia, Rhamdia quelen
      (Heptapteridae, Siluriformes). vasa encodes a member of the DEAD-box protein
      family of ATP-dependent RNA helicases. This protein is highly conserved among
      different organisms and its role is associated with RNA metabolism. In the
      majority of the investigated species, vasa is restricted to the germ cell lineage
      and its expression has been used to study germline development in many organisms,
      including fish. The deduced R. quelen vasa amino acid sequence displayed high
      similarity with Vasa protein sequences from other organisms, and did not cluster
      with PL10 or P68 DEAD-box protein subfamilies. We also reported that there is no
      other isoform for vasa mRNA in R. quelen gonads. Expression analysis by RT-PCR
      and qPCR showed vasa transcripts exclusively expressed in the germ cells of R.
      quelen gonads. R. quelen vasa mRNA was maternally inherited, and was detected in
      the migrating primordial germ cells (PGCs) until 264 h post-fertilization during
      embryonic and larval development. This work has characterized for the first time
      the full-length R. quelen vasa cDNA, and describes its expression patterns during
      R. quelen embryonic and larval development. Our results will contribute to the
      basic reproductive biology of this native species, and will support studies using
      vasa as a germ cell marker in different biotechnological studies, such as germ
      cell transplantation.

PMID- 29454091
TI  - Anlotinib inhibits angiogenesis via suppressing the activation of VEGFR2,
      PDGFRbeta and FGFR1.
AB  - Tumor cells recruit vascular endothelial cells and circulating endothelial
      progenitor cells to form new vessels to support their own growth and metastasis.
      VEGF, PDGF-BB and FGF-2 are three major pro-angiogenic factors and applied to
      promote angiogenesis. In this research, we demonstrated that anlotinib, a potent
      multi-tyrosine kinases inhibitor (TKI), showed a significant inhibitory effect on
      VEGF/PDGF-BB/FGF-2-induced angiogenesis in vitro and in vivo. Wound healing
      assay, chamber directional migration assay and tube formation assay indicated
      that anlotinib inhibited VEGF/PDGF-BB/FGF-2-induced cell migration and formation
      of capillary-like tubes in endothelial cells. Furthermore, anlotinib suppressed
      blood vessels sprout and microvessel density in rat aortic ring assay and chicken
      chorioallantoic membrane (CAM) assay. Importantly, according to our study, the
      anti-angiogenic effect of anlotinib is superior to sunitinib, sorafenib and
      nintedanib, which are three main anti-angiogenesis drugs in clinic.
      Mechanistically, anlotinib inhibits the activation of VEGFR2, PDGFRbeta and FGFR1
      as well their common downstream ERK signaling. Therefore, anlotinib is a
      potential agent to inhibit angiogenesis and be applied to tumor therapy.

PMID- 29454092
TI  - Analysis of human papillomavirus 16 E6, E7 genes and Long Control Region in
      cervical samples from Uruguayan women.
AB  - OBJECTIVE: This study aims to investigate the HPV16 variant distribution by
      sequence analyses of E6, E7 oncogenes and the Long Control Region (LCR), from
      cervical cells collected from Uruguayan women, and to reconstruct the
      phylogenetic relationships among variants. METHODS: Forty-seven HPV16 variants,
      obtained from women with HSIL, LSIL, ASCUS and NILM cytological classes were
      analyzed for LCR and 12 were further studied for E6 and E7. Detailed sequence
      comparison, genetic heterogeneity analyses and phylogenetic reconstruction were
      performed. RESULTS: A high variability was observed among LCR sequences, which
      were distributed in 18 different variants. E6 and E7 sequences exhibited novel
      non-synonymous substitutions. Uruguayan sequences mainly belonged to the European
      lineage, and only 5 sequences clustered in non-European branches; 3 of them in
      the Asian-American and North-American linage and 2 in an African branch.
      Additionally, 6 new variants from European and African clusters were identified.
      CONCLUSIONS: HPV16 isolates mainly belonged to the European lineage, though
      strains from African and Asian-American lineages were also identified. Herein is
      reported for the first time the distribution and molecular characterization of
      HPV16 variants from Uruguay, providing novel insights on the molecular
      epidemiology of this infectious disease in the South America. SYNOPSIS: A high
      variability among HPV 16 isolates mainly belonged to European lineage, provides
      an extensive sequence dataset from a country with high burden of cervical cancer.

PMID- 29454093
TI  - Silencing circular RNA hsa_circ_0000977 suppresses pancreatic ductal
      adenocarcinoma progression by stimulating miR-874-3p and inhibiting PLK1
      expression.
AB  - Circular RNAs (CircRNAs) are a novel type of endogenous noncoding RNAs that
      regulate target gene expression by interacting with microRNA (miRNA). Emerging
      evidence shows that dysregulation of circRNAs plays important roles in biological
      and pathological processes, including cancer development and progression. The
      functional role of circRNA in PDAC (pancreatic ductal adenocarcinoma) remains to
      be investigated. In this study, high throughput microarray assay revealed that
      hsa_circ_0000977 was aberrantly up-regulated in pancreatic cancer tissues; this
      was also validated by qRT-PCR. Silencing hsa_circ_0000977 suppressed pancreatic
      cancer cell proliferation and induced cell cycle arrest, which was simulated by
      hsa-miR-874-3p mimics and blocked by hsa-miR-874-3p inhibitor. Bioinformatics
      analysis predicted that there is an hsa_circ_0000977/hsa-miR-874-3p/PLK1 (Polo
      like kinase 1) axis in pancreatic cancer progression. Dual-luciferase reporter
      system and FISH assay validated the direct interaction of hsa_circ_0000977, hsa
      miR-874-3p, and PLK1. Western blot verified that inhibition of hsa_circ_0000977
      decreased PLK1 expression. Furthermore, silencing hsa_circ_0000977 suppressed
      pancreatic cancer growth in vivo. Altogether, silencing hsa_circ_0000977
      suppresses progression of pancreatic cancer by interacting with hsa-miR-874-3p
      and decreasing inhibiting PLK1 expression. Our results may provide a promising
      strategy for future diagnosis and treatment of pancreatic cancer.

PMID- 29454094
TI  - Synergistic activity of BET inhibitor BI 894999 with PLK inhibitor volasertib in
      AML in vitro and in vivo.
AB  - Interactions between a new potent Bromodomain and extraterminal domain (BET)
      inhibitor BI 894999 and the polo-like kinase (PLK) inhibitor volasertib were
      studied in acute myeloid leukemia cell lines in vitro and in vivo. We provide
      data for the distinct mechanisms of action of these two compounds with a
      potential utility in AML based on gene expression, cell cycle profile and
      modulation of PD biomarkers such as MYC and HEXIM1. In contrast to BI 894999,
      volasertib treatment neither affects MYC nor HEXIM1 expression, but augments and
      prolongs the decrease of MYC expression caused by BI 894999 treatment. In vitro
      combination of both compounds leads to a decrease in S-Phase and to increased
      apoptosis. In vitro scheduling experiments guided in vivo experiments in
      disseminated AML mouse models. Co-administration of BI 894999 and volasertib
      dramatically reduces tumor burden accompanied by long-term survival of tumor
      bearing mice and eradication of AML cells in mouse bone marrow. Together, these
      preclinical findings provide evidence for the strong synergistic effect of BI
      894999 and volasertib, warranting future clinical studies in patients with AML to
      investigate this paradigm.

PMID- 29454095
TI  - An esophageal adenocarcinoma susceptibility locus at 9q22 also confers risk to
      esophageal squamous cell carcinoma by regulating the function of BARX1.
AB  - Genome wide association studies (GWAS) have identified a series of genetic
      variants associated with the risk of esophageal adenocarcinoma (EAC)/Barrett's
      esophagus (BE), which was different from those loci for esophageal squamous cell
      carcinoma (ESCC). It is important to evaluate whether these susceptibility loci
      for EAC/BE are also implicated in ESCC development. In the current study, we
      analyzed genetic variants at 3p13, 9q22, 16q24 and 19p13 in a case-control study
      including 2139 ESCC patients and 2463 cancer-free controls in a Chinese
      population, and further characterized the biological relevance of genetic
      variants by functional assays. We found that the G allele of rs11789015 at 9q22,
      as compared with the A allele, was significantly associated with a decreased risk
      of ESCC with a per-allele odds ratio of 0.77 (95%CI, 0.65-0.90; P = 1.38 * 10-3),
      whereas the other three loci were not associated with ESCC risk. We further found
      that rs11789015-G allele correlated with decreased mRNA and protein levels of
      BARX1. Dual-luciferase reporter gene assay revealed that the A > G change at
      rs11789015 significantly decreased the promoter activity of BARX1. Both the mRNA
      and protein levels of BARX1 were significantly higher in ESCC tumor tissues
      compared with the corresponding normal tissues. Moreover, the deletion of BARX1
      substantially reduced ESCC cells growth, migration and invasion. In conclusion,
      these results suggest that genetic variants at 9q22 are associated with the risk
      of both EAC/BE and ESCC, possibly by regulating the function of BARX1.

PMID- 29454096
TI  - JAK/STAT inhibitors and other small molecule cytokine antagonists for the
      treatment of allergic disease.
AB  - OBJECTIVE: To provide an overview of janus kinase (JAK), chemoattractant receptor
      homologous molecule expressed on TH2 cells (CRTH2), and phosphodiesterase 4
      (PDE4) inhibitors in allergic disorders. DATA SOURCES: PubMed literature review.
      STUDY SELECTIONS: Articles included in this review discuss the emerging mechanism
      of action of small molecule inhibitors and their use in the treatment of atopic
      dermatitis (AD), asthma, and allergic rhinitis (AR). RESULTS: Allergic diseases
      represent a spectrum of diseases, including AD, asthma, and AR. For decades,
      these diseases have been primarily characterized by increased TH2 signaling and
      downstream inflammation. In recent years, additional research has identified
      disease phenotypes and subsets of patients with non-Th2 mediated inflammation.
      The increasing heterogeneity of disease has prompted investigators to move away
      from wide-ranging treatment approaches with immunosuppressive agents, such as
      corticosteroids, to consider more targeted immunomodulatory approaches focused on
      specific pathways. In the past decade, inhibitors that target JAK signaling,
      PDE4, and CRTH2 have been explored for their potential activity in models of
      allergic disease and therapeutic benefit in clinical trials. Interestingly,
      although JAK inhibitors provide an opportunity to interfere with cytokine
      signaling and could be beneficial in a broad range of allergic diseases, current
      clinical trials are focused on the treatment of AD. Conversely, both PDE4 and
      CRTH2 inhibitors have been evaluated in a spectrum of allergic diseases. This
      review summarizes the varying degrees of success that these small molecules have
      demonstrated across allergic diseases. CONCLUSION: Emerging therapies currently
      in development may provide more consistent benefit to patients with allergic
      diseases by specifically targeting inflammatory pathways important for disease
      pathogenesis.

PMID- 29454097
TI  - Improving sustained drug delivery from ophthalmic lens materials through the
      control of temperature and time of loading.
AB  - Although the possibility of using drug-loaded ophthalmic lens to promote
      sustained drug release has been thoroughly pursued, there are still problems to
      be solved associated to the different alternatives. In this work, we went back to
      the traditional method of drug loading by soaking in the drug solution and tried
      to optimize the release profiles by changing the temperature and the time of
      loading. Two materials commercially available under the names of CI26Y and
      Definitive 50 were chosen. CI26Y is used for intraocular lenses (IOLs) and
      Definitive 50 for soft contact lenses (SCLs). Three drugs were tested: an
      antibiotic, moxifloxacin, and two anti-inflammatories, diclofenac and ketorolac.
      Sustained drug release from CI26Y disks for, at least 15 days, was obtained for
      moxifloxacin and diclofenac increasing the loading temperature up to 60  degrees
      C or extending the loading time till two months. The sustained release of
      ketorolac was limited to about 8 days. In contrast, drug release from Definitive
      50 disks could not be improved by changing the loading conditions. An attempt to
      interpret the impact of the loading conditions on the drug release behavior was
      done using solid-state NMR and differential scanning calorimetry. These studies
      suggested the establishment of reversible, endothermic interactions between CI26Y
      and the drugs, moxifloxacin and diclofenac. The loading temperature had a slight
      effect on the mechanical and optical properties of drug loaded CI26Y samples,
      which still kept adequate properties to be used as IOL materials. The in vivo
      efficacy of CI26Y samples, drug loaded at 60  degrees C for two weeks, was
      predicted using a simplified mathematical model to estimate the drug
      concentration in the aqueous humor. The estimated concentrations were found to
      comply with the therapeutic needs, at least, for moxifloxacin and diclofenac.

PMID- 29454099
TI  - Two-Stage Hepatectomy vs One-Stage Major Hepatectomy with Contralateral Resection
      or Ablation for Advanced Bilobar Colorectal Liver Metastases.
AB  - BACKGROUND: Both 2-stage hepatectomy (TSH) and 1-stage hepatectomy (OSH)
      represent feasible strategies for resection of advanced bilobar colorectal liver
      metastases (CLM). However, the influence of the surgical approach on
      postoperative outcomes and overall survival (OS) is unknown. To define the
      optimal surgical approach for advanced bilobar CLM requiring right
      hemihepatectomy, we compared short-term and long-term outcomes after TSH and OSH
      with contralateral resection or radiofrequency ablation (RFA). STUDY DESIGN: We
      retrospectively reviewed 227 patients with bilobar CLM, who underwent right or
      extended right hepatectomy with treatment of synchronous CLM in segments I, II,
      and/or III, between 1998 and 2015. Postoperative outcomes and OS were compared
      between patients who underwent TSH and those who underwent OSH. RESULTS: Of the
      227 patients, 126 (56%) underwent at least the first stage of TSH, and 101 (44%)
      underwent OSH, 29 (13%) without RFA and 72 (32%) with RFA. Two-stage hepatectomy
      was associated with a lower incidence of postoperative major complications (14%
      vs 26%, p = 0.03) and postoperative hepatic insufficiency (6% vs 20%, p = 0.001)
      than OSH. The 5-year OS rate was higher for patients assigned to TSH than for
      those who underwent OSH (35% vs 24%, p = 0.016). Patients who completed both
      stages of TSH had a higher 5-year OS rate than patients who underwent OSH without
      RFA (50% vs 20%, p = 0.023) or OSH with RFA (50% vs 24%, p < 0.0001).
      CONCLUSIONS: In patients with advanced bilobar CLM, TSH is associated with fewer
      complications than OSH. Both TSH in intention-to-treat analysis and completed TSH
      in as-treated analysis were associated with better OS than OSH.

PMID- 29454098
TI  - Quantitative Imaging Features and Postoperative Hepatic Insufficiency: A Multi
      Institutional Expanded Cohort.
AB  - BACKGROUND: Post-hepatectomy liver insufficiency (PHLI) is a significant cause of
      morbidity and mortality after liver resection. Quantitative imaging analysis
      using CT scans measures variations in pixel intensity related to perfusion. A
      preliminary study demonstrated a correlation between quantitative imaging
      features of the future liver remnant (FLR) parenchyma from preoperative CT scans
      and PHLI. The objective of this study was to explore the potential application of
      quantitative imaging analysis in PHLI in an expanded, multi-institutional cohort.
      STUDY DESIGN: We retrospectively identified patients from 5 high-volume academic
      centers who developed PHLI after major hepatectomy, and matched them to control
      patients without PHLI (by extent of resection, preoperative chemotherapy
      treatment, age [+/-5 years], and sex). Quantitative imaging features were
      extracted from the FLR in the preoperative CT scan, and the most discriminatory
      features were identified using conditional logistic regression. Percent remnant
      liver volume (RLV) was defined as follows: (FLR volume)/(total liver volume) *
      100. Significant clinical and imaging features were combined in a multivariate
      analysis using conditional logistic regression. RESULTS: From 2000 to 2015, 74
      patients with PHLI and 74 matched controls were identified. The most common
      indications for surgery were colorectal liver metastases (53%), hepatocellular
      carcinoma (37%), and cholangiocarcinoma (9%). Two CT imaging features (FD1_4:
      image complexity; ACM1_10: spatial distribution of pixel intensity) were strongly
      associated with PHLI and remained associated with PHLI on multivariate analysis
      (p = 0.018 and p = 0.023, respectively), independent of clinical variables,
      including preoperative bilirubin and %RLV. CONCLUSIONS: Quantitative imaging
      features are independently associated with PHLI and are a promising preoperative
      risk stratification tool.

PMID- 29454100
TI  - Patient-Centered Outcomes after Laparoscopic Paraesophageal Hernia Repair.
AB  - BACKGROUND: The aim of this study is to investigate patient-centered quality of
      life (QOL) outcomes in patients undergoing laparoscopic paraesophageal hernia
      repair. STUDY DESIGN: We prospectively followed patients who underwent
      laparoscopic paraesophageal hernia repair between 2009 and 2016. The QOL outcomes
      were measured using the 36-Item Short Form Health Survey, GERD Health Related
      Quality of Life, Reflux Symptom Index, and Dysphagia score surveys administered
      preoperatively and at 3 weeks, 6 months, 1 year, and 2 years postoperatively.
      Postoperative QOL outcomes were compared with preoperative baseline scores using
      paired t-tests. RESULTS: Of 314 total patients who underwent laparoscopic
      paraesophageal hernia repair, 188 with adequate follow-up were included in
      analysis. Mean age was 69.1 +/- 11.8 years and 22.3% of studied subjects were
      male. Most of the cohort also underwent laparoscopic fundoplication (95.7%).
      Prevalent symptoms at initial presentation include heartburn (65.4%) and
      regurgitation (60.1%). Significant improvements between baseline and all
      postoperative time points were seen in Reflux Symptoms Index (3 weeks: p <
      0.0001, 6 months: p = 0.005, 1 year: p = 0.0004, and 2 years: p = 0.002) and GERD
      Health Related Quality of Life scores (3 weeks: p < 0.0001, 6 months: p = 0.0019,
      1 year: p < 0.0001, and 2 years: p = 0.0003). Dysphagia scores were worse at 3
      weeks but lost significance at all other time points. The 36-Item Short Form
      Health Survey measures of Energy/Fatigue (p = 0.0099), Emotional Well-Being (p =
      0.0393), Social Functioning (p = 0.0278), Pain (p = 0.0021), and Role Limitations
      Due to Physical Health (p = 0.0009) were significantly improved 2 years
      postoperatively. CONCLUSIONS: Laparoscopic paraesophageal hernia repair results
      in significantly improved QOL as measured by the 36-Item Short Form Health Survey
      at both short- and long-term intervals. Additionally, Reflux Symptom Index and
      GERD Health Related Quality of Life scores improved at all postoperative time
      points.

PMID- 29454101
TI  - Venous Thromboembolism after Inpatient Surgery in Administrative Data vs NSQIP: A
      Multi-Institutional Study.
AB  - BACKGROUND: Previous studies have documented significant differences between
      administrative data and registry data in the determination of postoperative
      venous thromboembolism (VTE). The goal of this study was to characterize the
      discordance between administrative and registry data in the determination of
      postoperative VTE. STUDY DESIGN: This study was performed using data from the
      American College of Surgeons NSQIP merged with administrative data from 8
      different hospitals (5 different medical centers) between 2013 and 2015.
      Occurrences of postoperative vein thrombosis (VT) and pulmonary embolism (PE) as
      ascertained by administrative data and NSQIP data were compared. In each
      situation where the 2 sources disagreed (discordance), a 2-clinician chart review
      was performed to characterize the reasons for discordance. RESULTS: The cohort
      used for analysis included 43,336 patients, of which 53.3% were female and the
      mean age was 59.5 years. Concordance between administrative and NSQIP data was
      worse for VT (kappa 0.57; 95% CI 0.51 to 0.62) than for PE (kappa 0.83; 95% CI
      0.78 to 0.89). A total of 136 cases of discordance were noted in the assessment
      of VT; of these, 50 (37%) were explained by differences in the criteria used by
      administrative vs NSQIP systems. In the assessment of postoperative PE,
      administrative data had a higher accuracy than NSQIP data (odds ratio for
      accuracy 2.86; 95% CI 1.11 to 7.14) when compared with the 2-clinician chart
      review. CONCLUSIONS: This study identifies significant problems in ability of
      both NSQIP and administrative data to assess postoperative VT/PE. Administrative
      data functioned more accurately than NSQIP data in the identification of
      postoperative PE. The mechanisms used to translate VTE measurement into quality
      improvement should be standardized and improved.

PMID- 29454102
TI  - Inflammation as a Possible Link Between Dyslipidemia and Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is the leading cause of dementia worldwide. This
      pathological condition is characterized not only by Abeta and tau accumulation in
      the central nervous system (CNS), but also by inflammation, processes that can
      lead to neurodegeneration. Besides that, other factors may contribute to the
      development of AD, such as dyslipidemias. Changes in lipid levels can either
      influence the activity of enzymes related to the protein deposition that occurs
      in this pathological condition, or enhance the peripheral and CNS immune
      responses. Furthermore, cholesterol-associated genes are frequently associated
      with AD. Here, we extensively reviewed the literature and, based on the existing
      evidences, we suggest inflammation as an important link between dyslipidemias and
      AD.

PMID- 29454103
TI  - Corrigendum to "Sparse asynchronous cortical generators can produce measurable
      scalp EEG signals" [Neuroimage 138 (2016) 123-133].

PMID- 29454105
TI  - Assessing the repeatability of absolute CMRO2, OEF and haemodynamic measurements
      from calibrated fMRI.
AB  - As energy metabolism in the brain is largely oxidative, the measurement of
      cerebral metabolic rate of oxygen consumption (CMRO2) is a desirable biomarker
      for quantifying brain activity and tissue viability. Currently, PET techniques
      based on oxygen isotopes are the gold standard for obtaining whole brain CMRO2
      maps. Among MRI techniques that have been developed as an alternative are dual
      calibrated fMRI (dcFMRI) methods, which exploit simultaneous measurements of BOLD
      and ASL signals during a hypercapnic-hyperoxic experiment to modulate brain blood
      flow and oxygenation. In this study we quantified the repeatability of a dcFMRI
      approach developed in our lab, evaluating its limits and informing its
      application in studies aimed at characterising the metabolic state of human brain
      tissue over time. Our analysis focussed on the estimates of oxygen extraction
      fraction (OEF), cerebral blood flow (CBF), CBF-related cerebrovascular reactivity
      (CVR) and CMRO2 based on a forward model that describes analytically the acquired
      dual echo GRE signal. Indices of within- and between-session repeatability are
      calculated from two different datasets both at a bulk grey matter and at a voxel
      wise resolution and finally compared with similar indices obtained from previous
      MRI and PET measurements. Within- and between-session values of intra-subject
      coefficient of variation (CVintra) calculated from bulk grey matter estimates 6.7
      +/- 6.6% (mean +/- std.) and 10.5 +/- 9.7% for OEF, 6.9 +/- 6% and 5.5 +/- 4.7%
      for CBF, 12 +/- 9.7% and 12.3 +/- 10% for CMRO2. Coefficient of variation (CV)
      and intraclass correlation coefficient (ICC) maps showed the spatial distribution
      of the repeatability metrics, informing on the feasibility limits of the method.
      In conclusion, results show an overall consistency of the estimated physiological
      parameters with literature reports and a satisfactory level of repeatability
      considering the higher spatial sensitivity compared to other MRI methods, with
      varied performance depending on the specific parameter under analysis, on the
      spatial resolution considered and on the study design.

PMID- 29454104
TI  - Functional brain connectivity is predictable from anatomic network's Laplacian
      eigen-structure.
AB  - How structural connectivity (SC) gives rise to functional connectivity (FC) is
      not fully understood. Here we mathematically derive a simple relationship between
      SC measured from diffusion tensor imaging, and FC from resting state fMRI. We
      establish that SC and FC are related via (structural) Laplacian spectra, whereby
      FC and SC share eigenvectors and their eigenvalues are exponentially related.
      This gives, for the first time, a simple and analytical relationship between the
      graph spectra of structural and functional networks. Laplacian eigenvectors are
      shown to be good predictors of functional eigenvectors and networks based on
      independent component analysis of functional time series. A small number of
      Laplacian eigenmodes are shown to be sufficient to reconstruct FC matrices,
      serving as basis functions. This approach is fast, and requires no time-consuming
      simulations. It was tested on two empirical SC/FC datasets, and was found to
      significantly outperform generative model simulations of coupled neural masses.

PMID- 29454106
TI  - Binocular vision adaptively suppresses delayed monocular signals.
AB  - A neutral density filter placed before one eye will produce a dichoptic imbalance
      in luminance, which attenuates responses to visual stimuli and lags neural
      signals from retina to cortex in the filtered eye. When stimuli are presented to
      both the filtered and unfiltered eye (i.e., binocularly), neural responses show
      little attenuation and no lag compared with their baseline counterpart. This
      suggests that binocular visual mechanisms must suppress the attenuated and
      delayed input from the filtered eye; however, the mechanisms involved remain
      unclear. Here, we used a Steady-State Visual Evoked Potential (SSVEP) technique
      to measure neural responses to monocularly and binocularly presented stimuli
      while observers wore an ND filter in front of their dominant eye. These data were
      well-described by a binocular summation model, which received the sinusoidal
      contrast modulation of the stimulus as input. We incorporated the influence of
      the ND filter with an impulse response function, which adjusted the input
      magnitude and phase in a biophysically plausible manner. The model captured the
      increase in attenuation and lag of neural signals for stimuli presented to the
      filtered eye as a function of filter strength, while also generating the filter
      phase-invariant responses from binocular presentation for EEG and psychophysical
      data. These results clarify how binocular visual mechanisms-specifically
      interocular suppression-can suppress the delayed and attenuated signals from the
      filtered eye and maintain normal neural signals under imbalanced luminance
      conditions.

PMID- 29454107
TI  - Archetype modeling methodology.
AB  - Clinical Information Models (CIMs) expressed as archetypes play an essential role
      in the design and development of current Electronic Health Record (EHR)
      information structures. Although there exist many experiences about using
      archetypes in the literature, a comprehensive and formal methodology for
      archetype modeling does not exist. Having a modeling methodology is essential to
      develop quality archetypes, in order to guide the development of EHR systems and
      to allow the semantic interoperability of health data. In this work, an archetype
      modeling methodology is proposed. This paper describes its phases, the inputs and
      outputs of each phase, and the involved participants and tools. It also includes
      the description of the possible strategies to organize the modeling process. The
      proposed methodology is inspired by existing best practices of CIMs, software and
      ontology development. The methodology has been applied and evaluated in regional
      and national EHR projects. The application of the methodology provided useful
      feedback and improvements, and confirmed its advantages. The conclusion of this
      work is that having a formal methodology for archetype development facilitates
      the definition and adoption of interoperable archetypes, improves their quality,
      and facilitates their reuse among different information systems and EHR projects.
      Moreover, the proposed methodology can be also a reference for CIMs development
      using any other formalism.

PMID- 29454109
TI  - Comparative evaluation of lignocellulolytic activities of filamentous cultures of
      monocentric and polycentric anaerobic fungi.
AB  - Sixteen strains of monocentric and polycentric anaerobic fungi were evaluated for
      cellulase, xylanase and esterase activities. Though strain level variations were
      observed among all genera, Neocallimastix and Orpinomyces strains exhibited the
      highest lignocellulolytic activities. The esterase activities of monocentric
      group of anaerobic fungi were better than the polycentric group.

PMID- 29454108
TI  - Detection of B. fragilis group and diversity of bft enterotoxin and antibiotic
      resistance markers cepA, cfiA and nim among intestinal Bacteroides fragilis
      strains in patients with inflammatory bowel disease.
AB  - We compared frequency of the members of B. fragilis group in 100 and 20 colon
      biopsy specimens of inflammatory bowel disease (IBD) and non-IBD patients. Agar
      dilution and PCR were orderly used to detect minimal inhibitory concentration of
      ampicillin, imipenem, and metronidazole, and carriage of related resistance genes
      cepA, cfi, and nim. B. fragilis group was detected in 38% of IBD (UC: 36/89;
      CD:1/11) and 25% (5/20) of non-IBD patients. While B. vulgatus (UC: 20/36, CD:
      1/2, control: 1/6); B. fragilis (UC: 18/36, CD: 1/2, control: 5/6); B. ovatus
      (UC: 2/36); B. caccae (UC: 1/36); and B. eggerthii (UC: 1/36) were characterized,
      colonization of B. thetaiotamicron, B. merdae, B. distasonis, B. stercoris and B.
      dorei species was not detected in these specimens. Co-existence of B. fragilis +
      B. vulgatus (5 patients) and B. vulgatus + B. caccae (1 patient) was detected
      just in UC patients. bft was detected among 31.5% (6/19) of B. fragilis strains
      in the IBD and 40% (2/5) in the non-IBD groups. Nearly, 73.6% of the strains from
      the patient group and 80% in control group harbored cepA; 31.5% and 20% in the
      patients and control groups harbored cfiA, and none of them harbored nim
      determinant. Co-occurrence of the cepA and cfiA was orderly detected in 10.5%
      (2/19) and 20% (1/5) of the strains in these groups. The resistance rates were
      detected as 95.8% (23/24 (to ampicillin (MIC range of <=0.5->=16 MUg/ml), 0% to
      metronidazole and 29.1% to imipenem (7/24, MIC range <=4-32 MUg/ml). Nearly 25%
      (6/24) of the strains were resistant to ampicillin and imipenem, simultaneously.
      No statistically significant difference was detected between the IBD and control
      groups for drug resistance phenotypes. Statistical analysis showed significant
      associations between resistance to ampicillin or imipenem and carriage of cepA or
      cfiA, respectively (p value = 0.0007). PCR results on the extracted plasmids
      confirmed their roles in carriage of cfiA and cepA. These data provide guide for
      antibiotic therapy and highlights wide distribution of beta-lactam resistant B.
      fragilis strains in patients with IBD and non-IBD intestinal disorders.

PMID- 29454110
TI  - Study of lipid metabolism by estimating the fat fraction in different breast
      tissues and in various breast tumor sub-types by in vivo 1H MR spectroscopy.
AB  - PURPOSE: To evaluate the utility of fat fraction (FF) for the differentiation of
      different breast tissues and in various breast tumor subtypes using in vivo
      proton (1H) magnetic resonance spectroscopy (MRS). METHODS: 1H MRS was performed
      on 68 malignant, 35 benign, and 30 healthy volunteers at 1.5 T. Malignant breast
      tissues of patients were characterized into different subtypes based on the
      differences in the expression of hormone receptors and the FF was calculated.
      Further, the sensitivity and specificity of FF to differentiate malignant from
      benign and from normal breast tissues of healthy volunteers was determined using
      receiver operator curve (ROC) analysis. RESULTS: A significantly lower FF of
      malignant (median 0.12; range 0.01-0.70) compared to benign lesions (median 0.28;
      range 0.02-0.71) and normal breast tissue of healthy volunteers (median 0.39;
      range 0.06-0.76) was observed. No significant difference in FF was seen between
      benign lesions and normal breast tissues of healthy volunteers. Sensitivity and
      specificity of 75% and 68.6%, respectively was obtained to differentiate
      malignant from benign lesions. For the differentiation of malignant from healthy
      breast tissues, 76% sensitivity and 74.5% specificity was achieved. Higher FF was
      seen in patients with ER-/PR- status as compared to ER+/PR+ patients. Similarly,
      FF of HER2neu+ tumors were significantly higher than in HER2neu- breast tumors.
      CONCLUSION: The results showed the potential of in vivo 1H MRS in providing
      insight into the changes in the fat content of different types of breast tissues
      and in various breast tumor subtypes.

PMID- 29454111
TI  - Combining Rosetta with molecular dynamics (MD): A benchmark of the MD-based
      ensemble protein design.
AB  - Computational protein design is a set of procedures for computing amino acid
      sequences that will fold into a specified structure. Rosetta Design, a commonly
      used software for protein design, allows for the effective identification of
      sequences compatible with a given backbone structure, while molecular dynamics
      (MD) simulations can thoroughly sample near-native conformations. We benchmarked
      a procedure in which Rosetta design is started on MD-derived structural ensembles
      and showed that such a combined approach generates 20-30% more diverse sequences
      than currently available methods with only a slight increase in computation time.
      Importantly, the increase in diversity is achieved without a loss in the quality
      of the designed sequences assessed by their resemblance to natural sequences. We
      demonstrate that the MD-based procedure is also applicable to de novo design
      tasks started from backbone structures without any sequence information. In
      addition, we implemented a protocol that can be used to assess the stability of
      designed models and to select the best candidates for experimental validation. In
      sum our results demonstrate that the MD ensemble-based flexible backbone design
      can be a viable method for protein design, especially for tasks that require a
      large pool of diverse sequences.

PMID- 29454112
TI  - Comparative proteomic analysis of the maize responses to early leaf senescence
      induced by preventing pollination.
AB  - The aim of this study was to explore the molecular mechanisms of induced leaf
      senescence by preventing pollination in maize using a proteomic method combined
      with other physiological methods. An elite maize inbred line Yu816 was selected
      for evaluation of its senescence mechanism. Phenotypic and chlorophyll content
      analysis revealed that the onset of leaf senescence occurred earlier in non
      pollinated (NONPOL) leaves than pollinated (POL) leaves. Leaf protein species of
      NONPOL and POL leaves were separately extracted and their proteomes were assessed
      using isobaric tags for relative and absolute quantitation (iTRAQ) analysis. A
      total of 4371 protein species were identified, of which 809 exhibited
      differentially altered abundance (P < 0.05). The identified protein species were
      related to diverse functions including photosystems, plant hormones, cell death,
      oxidative degradation, and protein metabolism, suggesting a potential signaling
      cascade for ear leaf senescence induced by pollination prevention. In addition,
      leaf total soluble sugar and leaf starch contents were remarkably higher in
      NONPOL plants than in POL plants. These findings suggest that induced leaf
      senescence might be associated with nutrient remobilization. Our results reveal a
      network of molecular mechanisms at the protein level and provide some insights
      into the early senescence mechanism in higher plants. Biological significance:
      The coordination between growth and timing for senescence is critical for maize
      production. However, the molecular mechanism of induced leaf senescence by
      preventing pollination in maize remains to be further elucidated at the proteomic
      level. Herein, we revealed some new protein species that are involved in hormone
      signaling, glycometabolism, oxidation-reduction, protein degradation and
      photosystem breakdown, and other biological processes that were not previously
      known to be associated with leaf senescence. This is the first large-scale
      proteomics study to examine induced leaf senescence in maize by preventing
      pollination.

PMID- 29454113
TI  - Identification of two novel CRESS DNA viruses associated with an Avipoxvirus
      lesion of a blue-and-gray Tanager (Thraupis episcopus).
AB  - The discovery of circular rep-encoding single stranded (CRESS) DNA viruses has
      increased spectacularly over the past decade. They represent the smallest animal
      viruses known worldwide infecting a wide variety of invertebrates and vertebrates
      in different natural and human-made environments. The extremely low similarity of
      nucleotide and protein sequences among different CRESS DNA genomes has challenged
      their classification. Moreover, the existence of capsid proteins (Cp) remains
      difficult to demonstrate which is crucial to understand the structural properties
      of these viruses. Here we describe two unclassified CRESS DNA viruses isolated
      from a cutaneous lesion, caused by a strain of Avipoxvirus, from a blue-and-gray
      tanager (Thraupis episcopus) in Southern Ecuador. Both viruses present
      replication-associated proteins (Rep) and one to two open reading frames (ORF),
      one of which represents a putative Cp. The two new Rep are long proteins
      characterized by the existence of the several highly conserved amino acid
      residues characteristic of rolling circle replication. Within the putative Cp we
      detected intrinsically disordered regions (IDR), potential protein and DNA
      binding regions, and nuclear localization signals (NLS), providing further
      evidence of presumed Cp. Despite being found on the same host lesion, both
      viruses show low similarity between each other (<60%) and other known CRESS DNA
      viruses. Furthermore, we analyze the evolutionary relationships within the CRESS
      DNA diversity. Additional sampling is needed to explore the possible pathogenic
      effects, prevalence and diversity (both phylogenetical and structural) of these
      viruses in wild bird populations.

PMID- 29454114
TI  - Mitochondria: Targeting mitochondrial reactive oxygen species with
      mitochondriotropic polyphenolic-based antioxidants.
AB  - Mitochondrial function and regulation of redox balance is fundamental in
      controlling cellular life and death pathways. Antioxidants have been used to
      counteract disruption of redox networks, normally associated with progressive
      loss of cell homeostasis and disease pathophysiology, although therapeutic
      success is limited mainly due to pharmacokinetic drawbacks. Attempts to improve
      mitochondrial function in a range of diseases spurred active drug discovery
      efforts. Currently, the most effective strategy to deliver drugs to mitochondria
      is the covalent link of lipophilic cations to the bioactive compound. Although
      targeting mitochondrial oxidative stress with antioxidants has been demonstrated,
      clinical use has been hampered by several challenges, with no FDA-approved drug
      so far. Development of new mitochondriotropic antioxidant agents based on dietary
      polyphenols has recently gained momentum. Due to their nature, mitochondria
      targeted multi-functional antioxidants can trigger stress responses and
      contribute to tissue protection through hormesis mechanisms, inhibiting excessive
      mitochondrial ROS production and associated diseases.

PMID- 29454115
TI  - Traumatic Spinal Injury: Global Epidemiology and Worldwide Volume.
AB  - BACKGROUND: Traumatic spinal injury (TSI) results from injury to bony,
      ligamentous, and/or neurologic structures of the spinal column and can cause
      significant morbidity and mortality. The global burden of TSI is poorly
      understood, so we performed a systematic review and meta-analysis to estimate the
      global volume of TSI. METHODS: We performed a systematic review through PubMed,
      Embase, and Cochrane Databases on TSI studies reported from 2000 to 2016.
      Collected data were used to perform a meta-analysis to estimate the annual
      incidence of TSI across World Health Organization regions and World Bank income
      groups using random-effect models. Incorporating global population figures, the
      annual worldwide volume of TSI was estimated. RESULTS: A total of 102 studies
      were included in the systematic review and 19 studies in the meta-analysis. The
      overall global incidence of TSI was 10.5 cases per 100,000 persons, resulting in
      an estimated 768,473 [95% confidence interval, 597,213-939,732] new cases of TSI
      annually worldwide. The incidence of TSI was higher in low- and middle-income
      countries (8.72 per 100,000 persons) compared with high-income countries (13.69
      per 100,000 persons). Road traffic accidents, followed by falls, were the most
      common mechanism of TSI worldwide. Overall, 48.8% of patients with TSI required
      surgery. CONCLUSIONS: TSI is a major source of morbidity and mortality throughout
      the world. Largely preventable mechanisms, including road traffic accidents and
      falls, are the main causes of TSI globally. Further investigation is needed to
      delineate local and regional TSI incidences and causes, especially in low- and
      middle-income countries.

PMID- 29454116
TI  - Cyst with a Twist! Diagnostic Dilemma.
AB  - Obstructive hydrocephalus secondary to posterior cranial fossa space-occupying
      lesions is common, and treatment includes shunting or removal of the causative
      lesion. The list of posterior fossa space-occupying lesions is exhaustive and
      includes tumors, cysts, and tumor-like conditions. In the setting of cancer, the
      first differential is usually a metastatic deposit. However, unrelated
      pathologies could coexist and may be overlooked. We hereby describe an unusual
      case of a posterior fossa cystic, suspected metastatic lesion presenting with
      moderate to severe hydrocephalus in a patient with oral cavity cancer on
      chemotherapy, which turned out to be cysticercosis on excision, leading to a
      diagnostic dilemma; hence the adage "cyst with a twist"!

PMID- 29454117
TI  - The Differentially Expressed Genes of Human Sporadic Cerebral Cavernous
      Malformations.
AB  - OBJECTIVES: To understand the development of sporadic cerebral cavernous
      malformations (SCCM) comprehensively, we analyzed gene expression profiles in
      SCCMs by gene microarray. METHODS: The total number of the specimens collected in
      our study was 14, 7 of which were SCCMs, and the others were controls that were
      obtained from normal brain vessels. The total RNA was extracted and hybridized
      with oligonucleotide array containing 21522 genes. The analysis of Gene Ontology
      (GO) items and molecular pathways was performed based on the GO and Kyoto
      Encyclopedia of Genes and Genomes databases. The gene coexpression networks were
      constructed to identify the core genes regulating the progression of SCCMs.
      RESULTS: A total of 785 probes, showing differentially expressed genes (DEGs)
      between the 2 groups, were found by the gene chips. According to the analysis
      based on GO and Kyoto Encyclopedia of Genes and Genomes, 286 GO terms and 53
      pathways were identified to be significantly relevant with the DEGs. All
      differential gene interactions were analyzed and the core genes were selected in
      the coexpression networks. CONCLUSIONS: The gene expression profiles obtained
      from SCCMs were significantly distinct from those of control brain vascular
      specimens. These DEGs are related to multiple molecular signal pathways, such as
      the mitogen-activated protein kinase pathway, cytokine-cytokine receptor
      interaction, focal adhesion, and inflammatory response. According to the analysis
      of the core genes selected in the gene coexpression networks, we postulated that
      CSF1R, XCL1, KCNMB1, RHOG, and TJP1 might exert enormous functions in the
      pathogenesis of SCCMs. However, further studies are required to aid in the
      clinical diagnosis and prevention of SCCMs.

PMID- 29454118
TI  - The Factors Affecting the Difficulty of Percutaneous Cylindrical Electrode
      Placement for Spinal Cord Stimulation.
AB  - OBJECTIVE: Optimal placement of electrodes is important for spinal cord
      stimulation. Factors affecting the difficulty of percutaneous electrode placement
      are not well known. In this study, we retrospectively evaluated the factors
      affecting the difficulty of percutaneous electrode placement. METHODS: We
      performed a retrospective analysis of 90 consecutive procedures of percutaneous
      cylindrical electrode implantation at the first author's institution. Age, sex,
      smoking state, body mass index, the duration of time from the beginning of pain
      syndrome to operation, diagnosis, the number of previous electrode placements,
      the previous electrode implantation period, the presence of axial low back pain,
      the electrode tip level, the pattern of electrode placement, and the reason for
      reimplantation were selected as factors associated with the success of electrode
      placement or the operation time of electrode placement. RESULTS: The number of
      previous electrode placements and the electrode tip level were independently
      associated with the operation time of electrode placement. According to both
      univariable and multivariable regression analyses, 1 previous electrode placement
      lengthened the operation time by approximately 15 minutes. No factors were
      significantly associated with the success of electrode placement. The more
      frequently that previous electrode placement was performed, the more difficult
      electrode placement tended to be. However, electrode reimplantation can be
      successful given extra time. CONCLUSIONS: This is the first study to evaluate
      factors affecting the difficulty of percutaneous electrode placement. A history
      of percutaneous cylindrical electrode placement did not affect the success of
      current placement, although it lengthened the operation time.

PMID- 29454119
TI  - Anatomic Study of Nutrient Foramina of Posterior Axis with Application to C2
      Pedicle Screw Placement.
AB  - OBJECTIVE: Pedicle screws placed into C2 necessitate a thorough understanding of
      this bone's unique anatomy. Although multiple landmarks and measurements have
      been used by surgeons, these are often varied in the literature with no
      consensus. Herein, we studied one recently proposed landmark using the nutrient
      foramina of the posterior aspect of C2 for pedicle screw placement. METHODS: On
      19 (38 sides) C2 dry bone specimens, the presence, size, location, and distance
      from the midline of the nutrient foramina found at the junction between the
      isthmus and lamina were documented and measured. In addition, to discern the
      source of the artery entering such foramina, an injected adult cadaver was
      dissected. RESULTS: The number of foramina ranged from 0-5 with a mean of 1.84.
      On 3 sides, no foramina were identified. The mean diameter of the foramina was
      0.57 mm. The location of the foramina was at position 1 on 9.5% of sides,
      position 2 on 66.4% of sides, and position 3 on 24.1% of sides. The mean
      horizontal distance from the midline of the spinous process of C2 to the foramina
      was 25.17 mm. In the cadaveric specimen, the source of the artery entering these
      C2 nutrient foramina was found to be distal branches of the deep cervical artery.
      CONCLUSIONS: We found the nutrient foramina of the C2 laminae are useful for
      pedicle screw placement. However, there are minor variations of the number and
      position of these structures. Lastly, on the basis of our study, 7.9% (n = 3) of
      sides will not have such foramina.

PMID- 29454120
TI  - Optic Nerve Atrophy Due to Long-Standing Compression by Planum Sphenoidale
      Meningioma.
AB  - PURPOSE: In this study we report an uncommon endoscopic endonasal image of an
      atrophic optic nerve as seen after surgical removal of a suprasellar meningioma.
      The peculiarity of this case is the long-lasting underestimated ocular
      symptomatology of the patient who reported a 15-year history of impairment of
      vision on her left eye. METHODS: A 51-year-old woman was admitted to our hospital
      complaining of a 15-year history of impairment of vision on her left eye. After
      making serendipitously the diagnosis of a suprasellar mass, we performed
      endoscopic endonasal surgery. RESULTS: The tumor was reached from below and
      removed safely, without manipulation of the optic pathways. At the end of tumor
      removal, the impressive left optic nerve atrophy due to enduring local tumor
      compression was visualized. CONCLUSIONS: To the best of our knowledge, no
      endoscopic endonasal image with such features has been provided in the pertinent
      literature. Possibly, this contribution will help identify damaged optic nerves
      during endoscopic endonasal surgery.

PMID- 29454121
TI  - Complications of Impulse Generator Exchange Surgery for Deep Brain Stimulation: A
      Single-Center, Retrospective Study.
AB  - BACKGROUND: Nonrechargeable deep brain stimulation impulse generators (IGs) with
      low or empty battery status require surgical IG exchange several years after
      initial implantation. The aim of this study was to investigate complication rates
      after IG exchange surgery and identify risk factors. METHODS: We retrospectively
      analyzed complications following IG exchange surgery from 2008 to 2015 in our
      department. Medical records of all patients who underwent IG exchange surgery
      were systematically reviewed. The shortest follow-up time was 19 months. RESULTS:
      From 2008 to 2015, 438 IGs were exchanged in 319 patients. Overall complication
      rate was 8.90%. Infection developed in 12 patients (2.74%). Six patients (1.37%)
      experienced local wound erosions. Hardware malfunctions were present in 11
      patients (2.51%), and local hemorrhage was observed in 3 cases (0.68%). Repeated
      fixation of the IG was required in 2 patients (0.46%). Traction of the connecting
      cables necessitated surgical revision in 2 patients (0.46%). In 2 cases (0.46%),
      the IG was placed abdominally or exchanged for a smaller device owing to patient
      discomfort resulting from the initial positioning. One 80-year-old patient
      (0.23%) had severely worsening heart failure and died 4 days after IG exchange
      surgery. CONCLUSIONS: IG exchange surgery, although often considered a minor
      surgery, was associated with a complication rate of approximately 9% in our
      center. Patients and physicians should understand the complication rates
      associated with IG exchange surgery because this information might facilitate
      selection of a rechargeable IG.

PMID- 29454122
TI  - Rope Jumping-Induced Traumatic Compression Fractures: the Underestimated Danger
      of Repetitive Axial Load Forces.
AB  - A non-osteoporotic adult presented with multilevel compression fractures at the
      apex of the thoracic kyphosis after strenuous rope jumping. Magnetic resonance
      imaging demonstrated diffuse bone marrow changes in the vertebral bodies with
      only a small unilateral endplate fracture. Besides highlighting the oftentimes
      neglected role of repetitive subpathological axial load forces in traumatic
      spinal injuries, the observed imaging pattern substantiates previous experimental
      studies which demonstrated that under cyclic axial loading the initial damage
      occurs in the cancellous regions of the bone (with observation of cracks with
      average length between 50-100 MUM), ultimately leading to a reduction in its
      elastic modulus. This pathophysiological mechanism, in which unmitigated
      propagation of trabecular microscopic cracks through the vertebral bone marrow
      precedes endplate fractures, may provide a rationale for recent proposals of
      targeted cement-augmentation in traumatic compression fractures with cement
      injection directed toward the regions of bone marrow changes.

PMID- 29454123
TI  - Cardiac Metastasis from Clivus Chordoma.
AB  - BACKGROUND: Chordomas are rare tumors showing locally aggressive nature and high
      rates of local recurrences. Distant metastases are infrequently reported and
      cardiac metastases are extremely rare. CASE DESCRIPTION: A 32-year-old woman had
      been diagnosed with a large chordoma involving the clivus. She received a total
      removal of the tumor and adjuvant intensity-modulated radiotherapy. Four and a
      half years after the surgery, she presented with multifocal lesions in the
      ventricles and the right atrium, although an open thoracotomy revealed chronic
      inflammation. Two years after finding the cardiac lesions, thoracoscopic biopsy
      of the chest wall lesion revealed metastatic chordoma. She received palliative
      imatinib for 2 weeks before she died of tumor progression. CONCLUSION: This case
      illustrates the metastatic potential of clivus chordoma, and the heart can be a
      site of metastasis.

PMID- 29454124
TI  - Brainstem Dose Constraints in Nonisometric Radiosurgical Treatment Planning of
      Trigeminal Neuralgia: A Single-Institution Experience.
AB  - BACKGROUND: CyberKnife stereotactic radiosurgery (SRS) for trigeminal neuralgia
      (TGN) administers nonisometric, conformational high-dose radiation to the
      trigeminal nerve with risk of subsequent hypoesthesia. METHODS: We performed a
      retrospective, single-institution review of 66 patients with TGN treated with
      CyberKnife SRS to compare outcomes from 2 distinct treatment periods: standard
      dosing (n = 38) and reduced dosing (n = 28). Standard and reduced dosing
      permitted a maximum brainstem dose of 45 Gy and 25 Gy, respectively, each with a
      prescription dose of 60 Gy. Primary and secondary outcomes were Barrow Neurologic
      Institute pain and numbness scores. Maximum brainstem dose, prepontine nerve
      length, and treatment history were recorded for their predictive contributions by
      logistic regression. RESULTS: After matching, patients in the standard dosing and
      reduced dosing groups were followed for a median of 25 months and 19.5 months,
      respectively. Mean trigeminal nerve length was 8.55 mm in the standard dosing
      group and 9.46 mm in the reduced dosing group. Baseline rates of poorly
      controlled pain were 97% and 88%, respectively, which improved to 23.4% and 8.3%,
      respectively (P < 0.001 for both). The baseline rates of bothersome numbness were
      null in both groups, and increased to 25% in the standard group (P = 0.006) and
      to 21% in the reduced group (P = 0.07). Regression analyses suggested that
      reduced brainstem exposure (P = 0.01), as well as a longer trigeminal nerve (P =
      0.01), were predictive of durable pain control. CONCLUSIONS: These outcomes
      demonstrate that a lower maximum brainstem dose can provide excellent pain
      control without affecting facial numbness. Longer nerves may achieve better long
      term outcomes and help optimize individual plans.

PMID- 29454125
TI  - Management of Skull Base Tumors in the Obstetric Population: A Case Series.
AB  - BACKGROUND: Neoplasms rarely present during pregnancy; however, increases in
      plasma volume, hormone release-induced growth, and tumor hypervascularity can
      cause rapidly progressive symptoms of varying severity, ranging from those not
      requiring intervention to those necessitating emergent operations. Here we
      describe an algorithm for the management of symptomatic neoplasms in the
      obstetric population and provide recommendations for surgical indications and
      timing. METHODS: Patients who presented to the skull base clinic at a large
      tertiary care hospital between 2010 and 2016 were reviewed to identify those who
      presented with a skull base tumor during pregnancy. RESULTS: Our study cohort
      comprised 9 women with a skull base tumor during pregnancy. Four patients
      presented with symptoms that necessitated emergent skull base surgery, and 5
      underwent surgery after delivery or were followed with continued surveillance.
      All operated patients had a World Health Organization grade I or II meningioma or
      schwannoma. There were no maternal complications. Based on our experience with
      this cohort, we have created a management algorithm. CONCLUSIONS: Management of a
      symptomatic tumor during pregnancy requires balancing the potential for curing
      the mother and the risk of harming the fetus. Trimester of pregnancy is the most
      critical factor in evaluating the need for urgent management. The second
      trimester is the optimal time for surgery, associated with the lowest risk for
      spontaneous abortion or preterm birth. The first and third trimesters are
      associated with increased risk of miscarriage and preterm labor, respectively.
      Induction of labor for preterm delivery, followed by surgery, may be appropriate
      in the early third trimester. Regardless of the perceived risk, however, all
      pregnant women with an emergent presentation should be offered surgery,
      regardless of trimester.

PMID- 29454126
TI  - Iatrogenic Spondylolisthesis Following Open Lumbar Laminectomy: Case Series and
      Review of the Literature.
AB  - OBJECTIVE: To present diagnosis and surgical management of postlaminectomy
      spondylolisthesis in patients without preoperative instability and a review of
      relevant literature. METHODS: Medical records and radiographic studies of 105
      patients who underwent first-time bilateral 1- to 4-level open laminectomies for
      degenerative lumbar disease at a single academic institution were reviewed.
      Patients who initially presented with listhesis and had additional discectomy or
      fusion procedures were excluded. RESULTS: Of 105 patients with laminectomies
      across 1-4 levels, 10 patients (9.5%; 5 men and 5 women with average age of 63.0
      +/- 11.2 years) developed subsequent iatrogenic spondylolisthesis at the same
      operative levels that required reoperation. New or worsening low back pain and
      lower extremity pain were reported over an average period of 19.0 +/- 17.5 months
      postoperatively. Imaging studies showed new spondylolisthesis that was not
      present before the index surgery, most commonly at L4-L5 level. All patients were
      treated surgically with posterior instrumented fusion. The average period between
      the first and second surgery was 32.6 +/- 19.9 months. Surgical reduction of
      spondylolisthesis resulted in significant clinical improvement of patients'
      symptoms. CONCLUSIONS: In patients without overt pre-existing instability,
      laminectomy for lumbar stenosis can disrupt spinal stability and result in
      iatrogenic spondylolisthesis. The extent of decompression of the facet joints,
      number of levels decompressed, and preoperative disc space height can help assess
      the risk of postoperative spondylolisthesis. Patients who develop recurrent
      radiculopathy after decompressive lumbar laminectomy should be evaluated for
      potential iatrogenic spondylolisthesis.

PMID- 29454127
TI  - Neurosurgery on a Pregnant Woman with Post Mortem Fetal Extrusion: An Unusual
      Case from Medieval Italy.
AB  - Trepanation is one of the most ancient and applied surgical treatments; several
      archaeologically documented cases are known, dated back from prehistory to the
      Middle Ages. This case study reports the anthropologic analysis of the skeletal
      remains of a young medieval woman and a fetus (Imola, Italy). The fetal remains
      were laid between her pelvis and lower limbs. A perforating injury was observed
      to her frontal bone. After assessing biologic profiles, we attempted to interpret
      the injury and to reconstruct possible circumstances of death. The lesion seems
      commensurate with a surgical intervention; signs of an osteogenic reaction were
      detected at its edges. It can be hypothesized that the survival of the woman
      undergoing the surgery was approximately 1 week and the fetus extruded after the
      burial. Thus, this case represents a unicum, spreading more light on the history
      of neurosurgery during the Early Middle Ages in Europe.

PMID- 29454129
TI  - Delayed Posttraumatic Subacute Lumbar Subarachnoid Hematoma: Case Report and
      Review of the Literature.
AB  - BACKGROUND: Traumatic spinal subarachnoid hematoma, associated or not with a
      concurrent subdural hematoma, has rarely been described. The evolution of such
      hematomas is heterogeneous. This study aims at defining the most accurate
      management, which is currently not standardized. CASE DESCRIPTION: A 20-year-old
      man, victim of a high-kinetic road accident 5 days before and with several
      nonneurologic nonsurgical vertebral fractures, experienced a sudden dorsolumbar
      pain radiating to his lower limbs. A rapidly progressive asymmetric paraparesis
      with loss of reflexes was noticed, associated with bilateral global hypoesthesia
      of the lower limbs and with acute urinary retention, whereas the anal tonicity
      was preserved (American Spinal Injury Association C). Magnetic resonance imaging
      scan revealed a conus medullaris compression at the level of the L1-L2 vertebrae
      by an intradural expansive mass. Immediate surgical decompression revealed a
      strictly subarachnoid hematoma. Venous bleeding was seen at the level of the
      conus medullaris and controlled. Pathologic examination of the clot excluded an
      underlying tumor or vascular abnormality. The complete coagulation profile was
      normal. CONCLUSION: Six weeks after surgery, the neurologic examination revealed
      only a slight tactile hypoesthesia of the left thigh. With only 4 reported cases,
      purely subarachnoid spinal hematomas remain widely rarer than epidural hematomas.
      The reported case possesses a certain number of peculiarities: young age, pure
      subarachnoid location, lumbar location, occurrence after a car accident, subacute
      onset, and excellent neurologic recovery. In our opinion, a symptomatic
      subarachnoid spinal hematoma should be surgically evacuated at the early phase so
      neurologic recovery can be expected.

PMID- 29454128
TI  - Preoperative 3-Dimensional Angiography Data and Intraoperative Real-Time Vascular
      Data Integrated in Microscope-Based Navigation by Automatic Patient Registration
      Applying Intraoperative Computed Tomography.
AB  - OBJECTIVE: To establish a workflow integrating preoperative 3-dimensional (3D)
      angiography data and intraoperative real-time vascular information in microscope
      based navigation for aneurysm and arteriovenous malformation (AVM) surgery.
      METHODS: In 7 patients (3 with AVMs and 4 with aneurysms), preoperative 3D
      rotational angiography or computed tomography (CT) or magnetic resonance
      angiography data were navigated applying a 32-slice movable CT scanner for low
      dose registration scanning. The 3D vasculature was segmented and visualized by
      microscope-based navigation along with navigated intraoperative real-time imaging
      data from indocyanin green angiography and duplex ultrasonography. RESULTS:
      Automatic registration applying intraoperative CT resulted in high accuracy
      (registration error, 0.80 +/- 0.79 mm). The effective radiation dose of the
      registration CT scans (0.28-0.42 mSv) was only approximately one-sixth of a
      standard diagnostic head CT scan. The 3D vessel architecture could be visualized
      accurately in the operating microscope heads-up display and on the navigation
      screens in the same projection as the view angle of the surgeon, both
      facilitating orientation in 3D space, providing a better understanding of
      anatomy. In addition, intraoperative real-time modalities could be coregistered
      with high precision, providing further information during the course of the
      vascular procedure. CONCLUSIONS: Registration CT imaging facilitates integrating
      preoperative and intraoperative vascular image data with a low registration error
      and low radiation exposure for the patient, improving the understanding of 3D
      vascular anatomy during surgery with easier identification of feeding vessels in
      AVMs, and of the projection and configuration of aneurysms.

PMID- 29454130
TI  - Abscess within a Glioblastoma: Mimicking a Matryoshka Doll.
AB  - BACKGROUND: Abscess coexisting within a brain tumor is rare. Case reports in the
      literature primarily consist of sellar pathology and parenchymal lesions,
      including meningioma, glioma, and metastases. We report a case of glioblastoma
      with an intratumoral abscess in a middle-aged patient with no prior invasive
      procedure or systemic focus of infection. CASE DESCRIPTION: A 45-year-old woman
      presented with new-onset generalized seizures and rapidly progressive left
      hemiparesis. Imaging showed a right frontal necrotic lesion with a peripherally
      enhancing wall and solid component posteriorly. There was no diffusion
      restriction within the lesion. She was afebrile, and there was no systemic focus
      of infection. With provisional diagnosis of malignant glioma, she underwent
      surgical resection of the lesion. A differential diagnosis of abscess was
      considered preoperatively because of the rapid increase in size of the lesion. At
      surgery, there was a pus-filled cavity with a few areas of grayish, soft, flimsy
      wall and thrombosed veins. This raised a strong suspicion of a coexisting abscess
      within a malignant glioma, which was confirmed by histopathologic and
      microbiologic examination. CONCLUSIONS: It is important for neurosurgeons to be
      aware of this rare entity. The treatment protocol remains controversial and is
      primarily guided by expert opinion. It is important to aggressively treat the
      patient with antibiotics followed by adjuvant therapy for malignancy. The timing
      and administration of adjuvant therapy are unclear. We suggest a delay of
      chemotherapy until at least 4 weeks of therapy with sensitive antibiotics.

PMID- 29454131
TI  - Self-Reported Headaches in Patients with Unruptured Intracranial Aneurysms
      Treated with the Pipeline Embolization Device.
AB  - INTRODUCTION: The objective of this study was to analyze patients' perceptions of
      their headaches both before and after Pipeline flow diversion treatment of their
      unruptured intracranial aneurysms, with the goal of identifying prognostic
      factors associated with headache patterns to improve predictions of overall
      outcomes. METHODS: We retrospectively identified 133 patients treated with the
      Pipeline embolization device (PED) between January 1, 2014, and December 31,
      2016, at an academic institution in the United States. Patients with at least 6
      months of clinical follow-up, who had completed a validated telephone survey
      assessing their headache perceptions before and after treatment of their UIAs,
      were included. RESULTS: Sixty patients (57.7%) responded to the questionnaire.
      Median aneurysm size was 6.3 mm. Thirty-two patients (53.3%) presented with
      headaches before treatment, which had a median intensity of 7 out of 10 (range, 3
      10). On postprocedural evaluation, 8 patients (25%) had complete resolution of
      their headaches. Of the 24 (75%) patients with persistent headaches, the
      frequency and severity of the headaches decreased or remained the same in most
      (58.3%) patients. Eleven (18.3%) patients had new-onset headaches. This study
      found an association between aneurysm size and a reduction in headache frequency
      and severity after PED treatment. No significant association was found between
      headache persistence, severity, or frequency and patient demographics, aneurysm
      characteristics, and other comorbidities. CONCLUSION: An overall improvement of
      headaches in patients with UIAs who underwent treatment with the PED was
      observed, particularly in patients harboring large aneurysms and who had
      presented with daily headaches.

PMID- 29454132
TI  - Diversion of complement-mediated killing by Bordetella.
AB  - The complement cascade participates in protection against bacterial infections,
      and pathogens, including Bordetella pertussis, have developed complement-evading
      strategies. Here we discuss current knowledge on B. pertussis complement evasion
      strategies and the role of antibody-dependent complement-mediated killing in
      protection against B. pertussis infection pointing out important knowledge gaps
      for further research to improve current pertussis vaccines.

PMID- 29454133
TI  - Prevalence and risk factors for neural axis anomalies in idiopathic scoliosis: a
      systematic review.
AB  - BACKGROUND: There is ongoing controversy about the routine use of magnetic
      resonance imaging (MRI) preoperatively in patients with presumed idiopathic
      scoliosis (IS). Routine MRI can help identify possible causes for the deformity
      and detect anomalies that could complicate deformity surgery. However, routine
      MRI increases health-care costs significantly and may reveal mild variations from
      normal findings without clinical relevance, which can still lead to anxiety and
      influence decision-making. PURPOSE: Given the necessity to make evidence-based
      decisions both in the light of quality of care and cost control, the aim of this
      review is to report the prevalence of neural axis anomalies in IS and to identify
      risk factors associated with these anomalies. STUDY DESIGN: A systematic review
      was carried out. METHODS: An electronic search of PubMed, Embase, Cochrane, and
      Cinahl until May 2017 was performed. Studies were assessed by two reviewers
      independently according to predetermined inclusion (MRI in presumed IS) and
      exclusion criteria (diagnosis other than IS). RESULTS: Fifty-one studies were
      included comprising 8,622 patients. In 981 patients, anomalies were found,
      resulting in an overall prevalence of 11.4%. The prevalence was 10.5%, 9.0%, and
      14.2% when screening was performed of all IS patients, preoperative patients, or
      patients with presumed risk factors. The prevalence of a syrinx (3.7%), an Arnold
      Chiari malformation (3.0%), or a combination of both (2.5%) was highest. Less
      frequent diagnoses included tethered cord (0.6%), an incidental malignancy
      (0.3%), and split cord malformations (0.2%). Risk factors for intraspinal
      anomalies included early-onset scoliosis, male gender, atypical curves, thoracic
      kyphosis, and abnormal neurologic findings such as reflexes and sensation.
      CONCLUSIONS: This systematic review shows that a significant number of patients
      have intraspinal anomalies on preoperative MRI in (presumed) IS. The prevalence
      of finding spinal axis abnormalities increases in preselected patient groups with
      specific risk factors.

PMID- 29454134
TI  - Back pain improves significantly following discectomy for lumbar disc herniation.
AB  - BACKGROUND CONTEXT: Although lumbar disc herniation (LDH) classically presents
      with lower extremity radiculopathy, there are patients who have substantial
      associated back pain. PURPOSE: The present study aims to determine if patients
      with LDH with substantial back pain improve with decompression alone. STUDY
      DESIGN: This is a longitudinal observational cohort study. PATIENT SAMPLE:
      Patients enrolled in the Quality and Outcomes Database with LDH and a baseline
      back pain score of >=5 of 10 who underwent single- or two-level lumbar discectomy
      only. OUTCOME MEASURES: Back and leg pain scores (0-10), Oswestry Disability
      Index (ODI), and EuroQoL 5D were measured. METHODS: Standard demographic and
      surgical variables were collected, as well as patient-reported outcomes at
      baseline and at 3 and 12 months postoperatively. RESULTS: The mean age of the
      cohort was 49.8 years and 1,195 (52.8%) were male. Mean body mass index was 30.1
      kg/m2. About half of the patients (1,103, 48.8%) underwent single-level
      discectomy and the other half (1,159, 51.2%) had two-level discectomy. Average
      blood loss was 44 cc. Most of the patients (2,217, 98%) were discharged home with
      routine postoperative care. The average length of stay was 0.53 days. At 3 and 12
      months postoperatively, there were statistically significant (p<.000)
      improvements in back pain (from 7.7 to 2.9 to 3.2), leg pain (from 7.5 to 2.3 to
      2.5), and ODI (from 26.2 to 11.6 to 11.2). Patients with a single-level
      discectomy, compared with patients with a two-level discectomy, had similar
      improvements in 3- and 12-month back pain, leg pain, and ODI scores. CONCLUSIONS:
      Patients with LDH who have substantial back pain can be counseled to expect
      improvement in their back pain scores 12 months after a discectomy.

PMID- 29454135
TI  - Short-term outcomes following posterior cervical fusion among octogenarians with
      cervical spondylotic myelopathy: a NSQIP database analysis.
AB  - BACKGROUND CONTEXT: Degenerative changes in the cervical spine occur in an age
      dependent manner. As the US population continues to age, the incidence of age
      dependent, multilevel, degenerative cervical pathologies is expected to increase.
      Similarly, the average age of patients with cervical spondylotic myelopathy (CSM)
      will likely trend upward. Posterior cervical fusion (PCF) is often the treatment
      modality of choice in the management of multilevel cervical spine disease.
      Although outcomes following anterior cervical fusion for degenerative disease
      have been studied among older patients (aged 80 years and older), it is unknown
      if these results extend to octogenarian patients undergoing PCF for the surgical
      management of CSM. PURPOSE: The present study aimed to quantify surgical outcomes
      following PCF for the treatment of CSM among the octogenarian patient population
      compared with patients younger than 80 years old. STUDY DESIGN/SETTING: This was
      a retrospective study that used the National Surgical Quality Improvement Program
      (NSQIP). PATIENT SAMPLE: The sample included patients aged 60-89 who had CSM and
      who underwent PCF from 2012 to 2014. OUTCOME MEASURES: The outcome measures were
      multimorbidity, prolonged length of stay (LOS), discharge disposition (to home or
      skilled nursing/rehabilitation facility), 30-day all-cause readmission, and 30
      day reoperation. METHODS: The NSQIP database was queried for patients with CSM
      (International Classification of Disease, Ninth Revision, Clinical Modification
      code 721.1) aged 60-89 who underwent PCF (Current Procedural Terminology code
      22600) from 2012 to 2014. Cohorts were defined by age group (60-69, 70-79, 80
      89). Data were collected on gender, race, elective or emergent status,
      inpatientor outpatient status, where patients were admitted from (home vs.
      skilled nursing facility), American Society of Anesthesiologists class,
      comorbidities, and single- or multilevel fusion. After controllingfor these
      variables, logistic regression analysis was used to compare outcome measures in
      the different age groups. RESULTS: A total of 819 patients with CSM who underwent
      PCF (416 aged 60-69, 320 aged 70-79, and 83 aged 80-89) were identified from 2012
      to 2014. Of the PCF procedures, 79.7% were multilevel. There were no significant
      differences in the odds of multimorbidity, prolonged LOS, readmission, or
      reoperation when comparing octogenarian patients with CSM with patients aged 60
      69 or 70-79. Patients aged 60-69 and 70-79 were significantly more likely to be
      discharged to home than patients over 80 (odds ratio [OR] 4.3, 95% confidence
      interval [CI] 1.8-10.4, p<.0001, and OR 2.7, 95% CI 1.1-6.4, p=.0005,
      respectively). CONCLUSIONS: Compared with patients aged 60-69 and 70-79,
      octogenarian patients with CSM were significantly more likely to be discharged to
      a location other than home following PCF. After controlling for patient
      comorbidities and demographics, 80- to 89-year-old patients with CSM who
      underwent PCF did not differ in other outcomes when compared with the other age
      cohorts. These results can improve preoperative risk counseling and surgical
      decision-making.

PMID- 29454136
TI  - What is fast ventricular tachycardia, and whether to worry about it.

PMID- 29454137
TI  - Mechanisms and management of refractory ventricular arrhythmias in the age of
      autonomic modulation.
AB  - Ventricular arrhythmias are responsible for hundreds of thousands of deaths every
      year. Catheter ablation of ventricular tachycardia (VT) is an essential component
      of the management of these life-threatening arrhythmias. However, in many
      patients, despite medical and interventional therapy, VT recurs. Furthermore,
      some VT substrates (mid-myocardial, left ventricular summit, and intraseptal) are
      not easily targeted because of limitations of currently available technology. In
      certain clinical settings, ventricular fibrillation (VF) episodes that have
      premature ventricular contraction triggers can also be targeted with catheter
      ablation. However, in most patients there is no clear VF trigger to target, and
      therefore polymorphic VT or VF cannot be adequately treated with catheter
      ablation. The autonomic nervous system plays a crucial role in all aspects of
      ventricular arrhythmias, yet interventions specific to the cardiac neuronal axis
      have been largely underutilized. This underutilization has been most pronounced
      in patients with structural heart disease. However, there is a growing body of
      literature on the physiology and pathophysiology of cardiac neural control and
      the benefits of neuromodulation to treat refractory ventricular arrhythmias in
      these patients. We present case-based examples of neuromodulatory interventions
      currently available and a review of the literature supporting their use.

PMID- 29454138
TI  - Prognostic implications of early monomorphic and non-monomorphic tachyarrhythmias
      in patients discharged with acute coronary syndrome.
AB  - BACKGROUND: The prognostic implication of early ventricular tachyarrhythmias
      (VTs) after acute coronary syndrome (ACS) remains unclear. OBJECTIVE: We sought
      to investigate the clinical outcomes of early monomorphic and non-monomorphic VTs
      that occur within 48 hours in patients after ACS. METHODS: We retrospectively
      reviewed the clinical outcomes of 2033 [mean age 67.0 +/- 13.4 years; 1486
      (73.1%) men] consecutive patients who presented with ACS from 2004 to 2015.
      RESULTS: A total of 67 (3.3%) and 90 (4.4%) patients developed early monomorphic
      or non-monomorphic VT, respectively. Killip class IV (odds ratio [OR] 3.05; 95%
      confidence interval [CI] 1.47-6.36; P < .01), creatine kinase level (OR 1.01; 95%
      CI 1.00-1.02 per 100 IU/L; P = .01), and left ventricular ejection fraction (OR
      0.96; 95% CI 0.94-0.99; P < .01) were independently associated with early
      monomorphic VT, whereas age (OR 0.98; 95% CI 0.97-0.99; P = .04), ST elevated
      myocardial infarction (OR 3.53; 95% CI 1.71-7.27; P < .01), Killip class IV (OR
      4.91; 95% CI 2.76-8.74; P < .01), diabetes mellitus (OR 0.48; 95% CI 0.28-0.81; P
      < .01), and left ventricular ejection fraction (OR 0.97; 95% CI 0.95-0.99; P <
      .01) were independently associated with early non-monomorphic VT. More patients
      with early monomorphic VT (n = 22 [32.8%]) died in hospital than those with non
      monomorphic VT (n = 16 [17.8%]) or without early VT (n = 133 [7.1%]; P < .01).
      After a mean follow-up of 67.8 +/- 43.2 months, 21 patients with early
      monomorphic VT (46.7%), 22 patients with early non-monomorphic VT (29.7%), and
      552 patients without early VT (31.7%) died. Both early monomorphic and non
      monomorphic VTs were associated with a long-term increase in sudden arrhythmic
      deaths and recurrent VTs. Nevertheless, only early monomorphic VT was shown to
      independently predict overall survival (hazard ratio 1.62; 95% CI 1.03-2.55; P =
      .04). CONCLUSION: Early monomorphic VT, but not early non-monomorphic VT,
      independently predicted all-cause mortality in patients with ACS who survived to
      hospital discharge.

PMID- 29454139
TI  - Implantation of the subcutaneous implantable cardioverter-defibrillator with
      truncal plane blocks.

PMID- 29454141
TI  - A cluster randomized pilot trial of a tailored worksite smoking cessation
      intervention targeting Hispanic/Latino construction workers: Intervention
      development and research design.
AB  - Construction workers have the highest smoking rate among all occupations (39%).
      Hispanic/Latino workers constitute a large and increasing group in the US
      construction industry (over 2.6 million; 23% of all workers). These minority
      workers have lower cessation rates compared to other groups due to their limited
      access to cessation services, and lack of smoking cessation interventions adapted
      to their culture and work/life circumstances. Formative research was conducted to
      create an intervention targeting Hispanic/Latino construction workers. This paper
      describes the intervention development and the design, methods, and data analysis
      plans for an ongoing cluster pilot two-arm randomized controlled trial comparing
      an Enhanced Care worksite cessation program to Standard Care. Fourteen
      construction sites will be randomized to either Enhanced Care or Standard Care
      and 126 participants (63/arm) will be recruited. In both arms, recruitment and
      intervention delivery occur around "food trucks" that regularly visit the
      construction sites. Participants at Enhanced Care sites will receive the
      developed intervention consisting of a single face-to-face group counseling
      session, 2 phone calls, and a fax referral to Florida tobacco quitline (QL).
      Participants at Standard Care sites will receive a fax referral to the QL. Both
      groups will receive eight weeks of nicotine replacement treatment and two follow
      up assessments at three and six months. Feasibility outcomes are estimated
      recruitment yield, barriers to delivering the intervention onsite, and rates of
      adherence/compliance to the intervention, follow-ups, and QL enrollment. Efficacy
      outcomes are point-prevalence and prolonged abstinence rates at six month follow
      up confirmed by saliva cotinine <15 ng/ml.

PMID- 29454140
TI  - Weight management in rural health clinics: The Midwest diet and exercise trial.
AB  - : Obesity prevalence is higher in rural compared to urban residents. Rural health
      clinics offer a potential venue for delivery of weight management. However,
      traditional programs require travel to attend on-site meetings which is
      impractical or inconvenient for rural residents. Clinic staff in most rural
      settings are unlikely to be trained to provide effective weight management.
      Remote delivery using group phone conferences (GP) or individual phone calls
      (IP), by staff associated with rural clinics eliminates the need for travel to
      attend on-site meetings. The effectiveness of these approaches will be the focus
      of this trial. Staff at five primary care clinics, serving primarily rural
      residents, will be trained to deliver GP and IP interventions and an enhanced
      usual care (EUC), (i.e., individual face-to-face meetings (~45 min) at clinic
      site, four times across 18 mos.). Two hundred overweight/obese adults (BMI >=
      25.0-45.0 kg/m2, age >= 21 yrs.) will be recruited through each clinic and
      randomized to GP (n = 80), IP (n = 80), or EUC (n = 40) to compare weight loss (0
      6 mos.), weight maintenance (7-18 mos.), and weight change during a 6 mo. no
      contact follow-up (19-24 mos.) between intervention arms. The GP and IP
      interventions will be identical in lesson plan content, diet, and physical
      activity. The only difference between groups will be the delivery format (group
      vs. individual) and session duration (GP ~45 min/session; IP ~15 min/session).
      Primary (body weight) and secondary outcomes (waist circumference,
      energy/macronutrient intake, physical activity) will be assessed at baseline, 6,
      12, 18 and 24 mos. Cost and contingent valuation analyses will also be completed.
      NCT REGISTRATION: NCT02932748.

PMID- 29454142
TI  - The levels of oxidative stress and antioxidant capacity in hibernating Nanorana
      parkeri.
AB  - The effect of hibernation on oxidative stress and antioxidant defense was
      assessed in the frog Nanorana parkeri which inhabits the southern Tibetan
      Plateau. We compared the indices of oxidative stress (GSSG/GSH), the degree of
      oxidative damage (content of carbonyl proteins and lipid peroxide products) and
      the activities of antioxidant enzymes (SOD, CAT, GPx, GST and GR) in liver,
      brain, heart and muscle of N. parkeri sampled during summer and winter. Obtained
      results showed that hibernation induced a significant decrease in the level of
      GSH in heart, liver, and muscle, while the ratio of GSSG/GSH markedly increased
      in all tissues except for muscle. Regarding oxidative damage, significant
      increases in TBARS were observed in all tissues of N. parkeri in the midst of
      hibernation, and the lipid peroxides level also clearly elevated in these tissues
      except the liver. In liver and brain, the level of carbonyl proteins was
      significantly higher in winter relative to summer. Additionally, the activity of
      antioxidant enzymes obviously reduced in the liver of hibernating N. parkeri. The
      total antioxidant capacity was also significantly lower in all tissues during
      winter than summer. In conclusion, hibernation in N. parkeri induced oxidative
      stress which was supported by oxidative damage to lipids and proteins with
      suppression of antioxidant defense.

PMID- 29454143
TI  - The osmorespiratory compromise in rainbow trout (Oncorhynchus mykiss): The
      effects of fish size, hypoxia, temperature and strenuous exercise on gill
      diffusive water fluxes and sodium net loss rates.
AB  - In the context of the osmorespiratory compromise, hypoxia and temperature have
      been little studied relative to exercise, and diffusive water flux rates (as
      assessed by 3H2O efflux) have received almost no attention. We investigated the
      effects of fish size, hypoxia, exercise and acute temperature increase on
      diffusive water flux rates and net sodium loss rates in juvenile rainbow trout.
      Trout weighing 13-50 g were used to determine the effects of fish size under
      normoxia. Thereafter 25-50 g trout were selected to assess the effects of
      different hypoxia levels (3.15, 5.25 and 8.40 KPa), time course of hypoxia (1 h
      8.40 KPa, 3 h 8.40 KPa, 1 h 8.40 KPa +1 h normoxic recovery, and 1 h 8.40 KPa + 3
      h normoxic recovery), strenuous exercise (5 min) and acute temperature challenge
      (transfer from 8  degrees C to 13  degrees C or to 18  degrees C). Small fish (13
      g) had higher diffusive water flux rates than larger fish, turning over >100% of
      their fractional body water pool per hour against 34% per hour for 50 g fish.
      Hypoxic exposure exerted a biphasic effect, increasing the diffusive water flux
      rate at 8.40 KPa and 5.25 KPa, while returning it to control levels at 3.15 KPa.
      All the levels of hypoxia increased net Na+ loss. One hour hypoxia (8.40 KPa)
      increased diffusive water flux rate while prolonged 3 h hypoxia (8.40 KPa), and
      short or prolonged normoxic recovery returned diffusive water flux rates to
      control levels. All the treatments over the time course of hypoxia and normoxic
      recovery increased net Na+ loss rates. Strenuous exercise increased both the
      diffusive water flux and net Na+ loss rates. Acute temperature rise increased
      diffusive water flux rates, with Q10 values of 4.03 for 8 to 13  degrees C and
      2.16 for 8 to 18  degrees C, but the net Na+ loss rate did not change. There was
      no significant correlation between diffusive water flux rate and net Na+ loss
      rates at different hypoxia levels, over the course of hypoxia and normoxic
      recovery, or during acute temperature stress. In contrast, we observed a
      significant correlation between diffusive water flux and net Na+ loss rates
      following exercise. Overall, diffusive water flux and sodium loss were regulated
      differently during acute temperature challenge and hypoxia, while following
      exercise the two parameters were regulated in a similar fashion.

PMID- 29454144
TI  - Natural Orifice Specimen Extraction during Laparoscopic Bowel Resection for
      Colorectal Endometriosis: Technique and Outcome.
AB  - STUDY OBJECTIVE: To present a detailed description of a modified natural orifice
      specimen extraction (NOSE) colectomy technique. We also report the postoperative
      outcomes of our prospective case series when compared with conventional
      laparoscopic bowel resection in a relatively large series of patients. DESIGN:
      Canadian Task Force classification II-1. SETTING: A university tertiary referral
      center. PATIENTS: The last 90 consecutive patients in our care with deep
      infiltrating endometriosis of the bowel are presented in this study. Patients
      were diagnosed at the 1st Department of Obstetrics and Gynecology, Semmelweis
      University, Budapest, Hungary. INTERVENTIONS: We performed laparoscopic bowel
      resection using the transrectal NOSE technique and compared the results of the
      new operative method (n = 30) with traditional laparoscopic bowel resection (n =
      60). MEASUREMENTS AND MAIN RESULTS: The median duration of surgery was 121
      minutes in the control group and 96 minutes in the NOSE group (p = .005).
      According to the Clavien-Dindo classification, we observed a severe, grade IIIb
      or higher, overall complication rate of 3.3% among all 90 patients. In the
      control group, anastomosis insufficiency occurred in 3.3% of patients (2/60
      cases), and in 1 patient with anastomotic leakage a rectovaginal fistula was
      observed (1.7%). There was no significant difference in the rates of severe
      postoperative complications (p = .55). The length of hospital stay in the control
      group was a median of 7 days (range, 5-13 days), whereas in the NOSE group it was
      6 days (range, 3-11 days) (p < .001). CONCLUSION: According to our findings, the
      use of NOSE colectomy offers a shorter recovery time and can eventually lead to a
      shorter surgery duration compared with traditional laparoscopic bowel resection.

PMID- 29454145
TI  - Vaginal Excision of a Large Gartner Duct Cyst.

PMID- 29454146
TI  - Matching Trends for the Fellowship in Minimally Invasive Gynecologic Surgery
      Since Participation in the National Residency Match Program.
AB  - OBJECTIVE: To evaluate the level of interest in the fellowship in minimally
      invasive gynecologic surgery (FMIGS) using data from the National Residency Match
      Program (NRMP) over the past 5 years. DESIGN: Retrospective report (Canadian Task
      Force classification II-2). SETTING: Publicly reported data from the NRMP.
      PARTICIPANTS: Applicants using the NRMP to match into fellowship training.
      INTERVENTIONS: Reporting matching trends for the gynecologic surgical
      subspecialty programs starting in 2014, when the FMIGS programs began
      participating in the NRMP. MEASUREMENTS AND MAIN RESULTS: From 2014 to 2018, the
      number of FMIGS positions increased from 28 to 38. Over the 5 application cycles,
      the FMIGS programs had the highest ratio of applicants to positions overall
      (range, 1.7-2.0 for FMIGS) of the surgical gynecologic subspecialty programs
      analyzed (Gynecologic Oncology, Female Pelvic Medicine and Reconstructive
      Surgery, and Reproductive Endocrinology and Infertility). CONCLUSIONS: Since the
      FMIGS programs began participating in the NRMP in 2014, the FMIGS match has been
      highly competitive as a gynecologic surgical subspecialty, suggesting a high
      level of interest from residency graduates. This may reflect growing recognition
      that there is a body of knowledge unique to minimally invasive gynecologic
      surgeons.

PMID- 29454147
TI  - Factors Associated with Malignancy in Hysteroscopically Resected Endometrial
      Polyps: A Systematic Review and Meta-Analysis.
AB  - In this study, we aimed to estimate the frequency of premalignant and malignant
      lesions in endometrial polyps, and to evaluate associated clinical and
      demographic factors. A literature search was performed in major databases and the
      gray literature using the terms polyps OR endometrial polyp AND endometrial
      neoplasms OR endometrial cancer OR endometrial hyperplasia OR malignan*. Studies
      describing the frequency of premalignant and malignant lesions in endometrial
      polyps and any clinical or demographic factors associated with malignant lesions
      extracted using hysteroscopy were considered eligible. Independent investigators
      selected the studies and extracted the data. A meta-analysis was performed using
      a random-effects model and meta-regression. We identified 37 studies (comprising
      21,057 patients) of endometrial polyps. The prevalence of premalignant and
      malignant lesions was 3.4% (95% confidence interval [CI], 2.8-4.1; I2, 80.5%).
      Abnormal uterine bleeding (prevalence ratio [PR], 1.47; 95% CI, 1.27-1.69; I2,
      82.4%), menopausal status (PR, 1.67; 95% CI, 1.48-1.89; I2, 78.4%), age >60 years
      (PR, 2.41; 95% CI, 1.84-3.16; I2, 81.5%), diabetes mellitus (PR, 1.76; 95% CI,
      1.43-2.16; I2, 0.0%), systemic arterial hypertension (PR, 1.50; 95% CI, 1.20
      1.88; I2, 75.9%), obesity (PR, 1.41; 95% CI:1.13-1.76; I2, 41.2%), and tamoxifen
      use (PR, 1.53; 95% CI, 1.06-2.21; I2, 0.0%) were associated with endometrial
      polyp malignancy. However, breast cancer (PR, 0.83; 95% CI, 0.44-1.57; I2, 0.0%),
      hormonal therapy (PR, 0.93; 95% CI, 0.67-1.30; I2, 31.7%), parity (PR, 0.87; 95%
      CI, 0.39-1.96; I2, 78.1%), and endometrial polyp size (PR, 1.05; 95% CI, 0.70
      1.57; I2, 44.7%) were not associated with malignancy of endometrial polyps. Three
      of every 100 women with clinically recognized polyps, a condition associated with
      specific clinical and demographic factors, will harbor premalignant or malignant
      lesions.

PMID- 29454148
TI  - 68Ga[Ga]-Galmydar: Biodistribution and radiation dosimetry studies in rodents.
AB  - INTRODUCTION: 68Ga[Ga]-Galmydar is an avid transport substrate of ABCB1 (P
      Glycoprotein; 170kDa plasma membrane protein), breast cancer resistance protein
      (BCRP; ABCG2; 72kDa), penetrates human epidermal carcinoma (KB3-1), breast cancer
      (MCF7), embryonic kidney (HEK 293) tumor cells and rat cardiomyoblasts, and
      localizes within the mitochondria of tumor and myocardium cells. 68Ga[Ga]
      Galmydar excretes from blood pool quickly, and shows stable retention within rat
      myocardium in vivo for extended periods, therefore, the agent shows potential to
      enable myocardial perfusion imaging. The PET tracer also demonstrates ability to
      probe viability of the blood brain barrier (BBB) in WT mice compared with their
      mdr1a/1b(-/-) (dKO) and mdr1a/1b/ABCG2(-/-/-) (t-KO) counterparts. Herein, we
      report dosimetry data for 68Ga[Ga]-Galmydar in mice, and extrapolate that
      information to determine effective dose (ED) for human studies. METHODS: To
      further assess safety profiles of 68Ga[Ga]-Galmydar for enabling its deployment
      as a PET imaging probe for biomedical imaging in vivo, we estimated human
      radiation dosimetry extrapolated from mice biodistribution data. To accomplish
      this objective, 68Ga[Ga]-Galmydar was injected intravenously into tails, mice
      were euthanized, organs harvested (5min, 15min, 30min, 60min, 120min), counted,
      radiation doses to each organ, and whole body were also determined. RESULTS: The
      effective dose (ED) have been found to be 0.021mGy/MBq in males and 0.023mGy/MBq
      in females. The highest radiation dose was estimated to the kidneys with a value
      of 0.17mGy/MBq for males and 0.19mGy/MBq for females with contribution from
      activity in the urine prior to excretion. The critical organ in humans has been
      determined to be the gall bladder. These data provide preliminary projections on
      human dosimetry derived from rodent estimates thus providing platform for further
      validation of dosimetry analysis in human subjects. CONCLUSIONS: Combined data
      obtained from radiation dosimetry studies in mice indicate that 68Ga[Ga]-Galmydar
      would be safe for further evaluation of dosimetry toxicity and myocardial
      perfusion PET imaging in humans.

PMID- 29454149
TI  - Study of manganese binding to the ferroxidase centre of human H-type ferritin.
AB  - Ferritins are ubiquitous and conserved proteins endowed with enzymatic
      ferroxidase activity, that oxidize Fe(II) ions at the dimetal ferroxidase centre
      to form a mineralized Fe(III) oxide core deposited within the apo-protein shell.
      Herein, the in vitro formation of a heterodimetal cofactor constituted by Fe and
      Mn ions has been investigated in human H ferritin (hHFt). Namely, Mn and Fe
      binding at the hHFt ferroxidase centre and its effects on Fe(II) oxidation have
      been investigated by UV-Vis ferroxidation kinetics, fluorimetric titrations,
      multifrequency EPR, and preliminary Mossbauer spectroscopy. Our results show that
      in hHFt, both Fe(II) and Mn(II) bind the ferroxidase centre forming a Fe-Mn
      cofactor. Moreover, molecular oxygen seems to favour Mn(II) binding and increases
      the ferroxidation activity of the Mn-loaded protein. The data suggest that Mn
      influences the Fe binding and the efficiency of the ferroxidation reaction. The
      higher efficiency of the Mn-Fe heterometallic centre may have a physiological
      relevance in specific cell types (i.e. glia cells), where the concentration of Mn
      is the same order of magnitude as iron.

PMID- 29454150
TI  - Assessment of cervical stiffness in axial rotation among chronic neck pain
      patients: A trial in the framework of a non-manipulative osteopathic management.
AB  - BACKGROUND: Cervical stiffness is a clinical feature commonly appraised during
      the functional examination of cervical spine. Measurements of cervical stiffness
      in axial rotation have not been reported for patients with neck pain. The purpose
      of this study was to investigate cervical spine stiffness in axial rotation among
      neck pain patients and asymptomatic subjects, and to analyze the impact of
      osteopathic management. METHODS: Thirty-five individuals (17 patients) were
      enrolled. Measurements were carried out for left-right axial rotation using a
      torque meter device, prior and after intervention. Passive range of motion,
      stiffness, and elastic-and neutral zone magnitudes were analyzed. Pain intensity
      was also collected for patients. The intervention consisted in one single session
      of non-manipulative osteopathic treatment performed in both groups. FINDINGS: A
      significant main effect of intervention was found for total range of motion and
      neutral zone. Also, treatment by group interaction was demonstrated for neutral-,
      elastic zone, stiffness in right axial rotation, and for total neutral zone.
      Significant changes were observed in the clinical group after intervention,
      indicating elastic zone decrease and neutral zone increase. In contrast, no
      significant alteration was detected for the control group. INTERPRETATIONS:
      Stiffness characteristics of the cervical spine in axial rotation are prone to be
      altered in patients with neck pain, but seem to be relieved after a session of
      non-manipulative manual therapeutic techniques. Further investigations, including
      randomized clinical trials with various clinical populations and therapeutic
      modalities, are needed to confirm these preliminary findings.

PMID- 29454151
TI  - Humoral response to John Cunningham virus during pregnancy in multiple sclerosis.
AB  - BACKGROUND: Pregnancy induces an immunosuppressive state in the mother to ensure
      immunological acceptance of the foetus. Impairment of cell-mediated immune
      responses may render the mother susceptible to intracellular pathogens. It is not
      presently known whether pregnancy alters the immunosurveillance for John
      Cunningham virus (JCV), an opportunistic pathogen associated with natalizumab
      treatment for multiple sclerosis (MS). OBJECTIVE: To evaluate whether the humoral
      immune response to JCV is altered during pregnancy among MS patients and healthy
      controls to get insight to potential pregnancy-induced alterations related to
      immune response to JCV during pregnancy. METHODS: Serum anti-JCV-antibody-indices
      (JCV-Ab-index) were determined by a two-step second-generation enzyme-linked
      immunosorbent assay in 49 MS patients during and after pregnancy and in 49
      healthy controls during pregnancy. For comparison, total IgG levels and
      antibodies against Epstein-Barr, cytomegalo and measles viruses were similarly
      measured. RESULTS: The JCV-Ab-indices of MS patients were not altered during the
      pregnancy (1st vs. 3rd trimester, 0.62 vs. 0.77, p = 0.99). Contrary to this, in
      the healthy controls JCV-Ab-indices (p = 0.005), antibody levels to the other
      viruses, and total IgG levels (p < 0.0001) decreased significantly during
      pregnancy. CONCLUSIONS: JCV-Ab levels remain unaltered during MS pregnancy, while
      the total IgG concentration is reduced/diluted due to increasing plasma volumes
      during the course of pregnancy. This may imply a biologically significant
      alteration in the immune response to JCV during MS pregnancy.

PMID- 29454152
TI  - The influence of biogenic amines on Th17-mediated immune response in multiple
      sclerosis.
AB  - Biogenic amines are direct mediators of interactions between immune and nervous
      systems implicated in the pathogenesis of multiple sclerosis (MS). Recently,
      great attention has been drawn to studying the effects of biogenic amines on Th17
      cells, which play one of the central roles in the development of inflammatory
      lesions in MS. Results of these studies suggest that, depending on the activation
      of particular receptors, biogenic amines can both enhance and inhibit Th17-cell
      functions. Based on these data, targeting biogenic amines and their receptors
      could be explored as a new kind of additional disease-modifying treatment of MS.

PMID- 29454153
TI  - Muscle carnosine in experimental autoimmune encephalomyelitis and multiple
      sclerosis.
AB  - BACKGROUND: Muscle carnosine is related to contractile function (Ca++ handling)
      and buffering of exercise-induced acidosis. As these muscular functions are
      altered in Multiple Sclerosis (MS) it is relevant to understand muscle carnosine
      levels in MS. METHODS: Tibialis anterior muscle carnosine was measured in an
      animal MS model (EAE, experimental autoimmune encephalomyelitis, n = 40) and
      controls (CON, n = 40) before and after exercise training (EAEEX, CONEX, 10d, 1
      h/d, 24 m/min treadmill running) or sedentary conditions (EAESED, CONSED). Human
      m. vastus lateralis carnosine of healthy controls (HC, n = 22) and MS patients (n
      = 24) was measured. RESULTS: EAE muscle carnosine levels were decreased (p <
      .0001) by ~ 40% to ~ 64% at 10d and 17d following EAE induction (respectively)
      regardless of exercise (p = .823). Similarly, human MS muscle carnosine levels
      were decreased (- 25%, p = .03). CONCLUSION: Muscle carnosine concentrations in
      an animal MS model and MS patients are substantially reduced. In EAE exercise
      therapy does not restore this.

PMID- 29454154
TI  - Age-related functional changes in domain-specific medial temporal lobe pathways.
AB  - There is now converging evidence from studies in animals and humans that the
      medial temporal lobes (MTLs) harbor anatomically distinct processing pathways for
      object and scene information. Recent functional magnetic resonance imaging
      studies in humans suggest that this domain-specific organization may be
      associated with a functional preference of the anterior-lateral part of the
      entorhinal cortex (alErC) for objects and the posterior-medial entorhinal cortex
      (pmErC) for scenes. As MTL subregions are differentially affected by aging and
      neurodegenerative diseases, the question was raised whether aging may affect the
      2 pathways differentially. To address this possibility, we developed a paradigm
      that allows the investigation of object memory and scene memory in a mnemonic
      discrimination task. A group of young (n = 43) and healthy older subjects (n =
      44) underwent functional magnetic resonance imaging recordings during this novel
      task, while they were asked to discriminate exact repetitions of object and scene
      stimuli from novel stimuli that were similar but modified versions of the
      original stimuli ("lures"). We used structural magnetic resonance images to
      manually segment anatomical components of the MTL including alErC and pmErC and
      used these segmented regions to analyze domain specificity of functional
      activity. Across the entire sample, object processing was associated with
      activation of the perirhinal cortex (PrC) and alErC, whereas for scene
      processing, activation was more predominant in the parahippocampal cortex and
      pmErC. Functional activity related to mnemonic discrimination of object and scene
      lures from exact repetitions was found to overlap between processing pathways and
      suggests that while the PrC-alErC pathway was more involved in object
      discrimination, both pathways were involved in the discrimination of similar
      scenes. Older adults were behaviorally less accurate than young adults in
      discriminating similar lures from exact repetitions, but this reduction was
      equivalent in both domains. However, this was accompanied by significantly
      reduced domain-specific activity in PrC in older adults compared to what was
      observed in the young. Furthermore, this reduced domain-specific activity was
      associated to worse performance in object mnemonic discrimination in older
      adults. Taken together, we show the fine-grained functional organization of the
      MTL into domain-specific pathways for objects and scenes and their mnemonic
      discrimination and further provide evidence that aging might affect these
      pathways in a differential fashion. Future experiments will elucidate whether the
      2 pathways are differentially affected in early stages of Alzheimer's disease in
      relation to amyloid or tau pathology.

PMID- 29454155
TI  - Immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): Approaches on
      special subgroups and unresolved burning questions.
AB  - Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment
      strategy of advanced non-small cell lung cancer (NSCLC). Beyond the already
      approved indications in first- and second-line setting of advanced NSCLC, new
      data has recently emerged demonstrating its efficacy in locally advanced disease
      as maintenance after chemo-radiotherapy and currently several trials are also
      exploring its efficacy in earlier stages of the disease to evaluate whether these
      results could be extrapolated to the adjuvant setting. With the advent of all
      these new therapies, their potential in other thoracic malignancies such as
      mesothelioma and small-cell lung cancer are also being evaluated with encouraging
      preliminary data that endorses their short-term incorporation as new therapeutic
      options in these thoracic malignancies. However, despite all these new evidence,
      there are still several open questions that remain to be solved like the use of
      immune agents in special subpopulations such as elderly or fragile patients or
      the case of patients with brain metastases or autoimmune disorders. In addition
      some other open questions remain with regards ICIs activity in patients receiving
      corticosteroid or antibiotics, the potential use in oncogenic addicted tumours,
      as well as the safety of retreatment after the onset of immune-related adverse
      events (ir-AE) or the optimal dose schedule or time on treatment for ICIs
      administration. Herein, we propose to address all these questions, reviewing most
      recent evidence available in order to give readers some practical advises and
      guidance on how to deal with these challenges when treating NSCLC patients with
      immunotherapy.

PMID- 29454156
TI  - The GluN2B subunit represents a major functional determinant of NMDA receptors in
      human induced pluripotent stem cell-derived cortical neurons.
AB  - Abnormal signaling pathways mediated by N-methyl-d-aspartate receptors (NMDARs)
      have been implicated in the pathogenesis of various CNS disorders and have been
      long considered as promising points of therapeutic intervention. However, few
      efforts have been previously described concerning evaluation of therapeutic
      modulators of NMDARs and their downstream pathways in human neurons with
      endogenous expression of NMDARs. In the present study, we assessed expression,
      functionality, and subunit composition of endogenous NMDARs in human induced
      pluripotent stem cell (hiPSC)-derived cortical neurons (iCell Neurons and iCell
      GlutaNeurons). We initially confirmed the expected pharmacological response of
      iCell Neurons and iCell GlutaNeurons to NMDA by patch-clamp recordings.
      Subsequent pharmacological interrogation using GluN2 subunit-selective
      antagonists revealed the predominance of GluN2B in both iCell Neurons and iCell
      GlutaNeurons. This observation was also supported by qRT-PCR and Western blot
      analyses of GluN2 subunit expression as well as pharmacological experiments using
      positive allosteric modulators with distinct GluN2 subunit selectivity. We
      conclude that iCell Neurons and iCell GlutaNeurons express functional GluN2B
      containing NMDARs and could serve as a valuable system for development and
      validation of GluN2B-modulating pharmaceutical agents.

PMID- 29454157
TI  - Nanofibrous PLGA electrospun scaffolds modified with type I collagen influence
      hepatocyte function and support viability in vitro.
AB  - : A major challenge of maintaining primary hepatocytes in vitro is progressive
      loss of hepatocyte-specific functions, such as protein synthesis and cytochrome
      P450 (CYP450) catalytic activity. We developed a three-dimensional (3D)
      nanofibrous scaffold made from poly(l-lactide-co-glycolide) (PLGA) polymer using
      a newly optimized wet electrospinning technique that resulted in a highly porous
      structure that accommodated inclusion of primary human hepatocytes. Extracellular
      matrix (ECM) proteins (type I collagen or fibronectin) at varying concentrations
      were chemically linked to electrospun PLGA using amine coupling to develop an in
      vitro culture system containing the minimal essential ECM components of the liver
      micro-environment that preserve hepatocyte function in vitro. Cell-laden
      nanofiber scaffolds were tested in vitro to maintain hepatocyte function over a
      two-week period. Incorporation of type I collagen onto PLGA scaffolds (PLGA
      Chigh: 100 ug/mL) led to 10-fold greater albumin secretion, 4-fold higher urea
      synthesis, and elevated transcription of hepatocyte-specific CYP450 genes
      (CYP3A4, 3.5-fold increase and CYP2C9, 3-fold increase) in primary human
      hepatocytes compared to the same cells grown within unmodified PLGA scaffolds
      over two weeks. These indices, measured using collagen-bonded scaffolds, were
      also higher than scaffolds coupled to fibronectin or an ECM control sandwich
      culture composed of type I collagen and Matrigel. Induction of CYP2C9 activity
      was also higher in these same type I collagen PLGA scaffolds compared to other
      ECM-modified or unmodified PLGA constructs and was equivalent to the ECM control
      at 7 days. Together, we demonstrate a minimalist ECM-based 3D synthetic scaffold
      that accommodates primary human hepatocyte inclusion into the matrix, maintains
      long-term in vitro survival and stimulates function, which can be attributed to
      coupling of type I collagen. STATEMENT OF SIGNIFICANCE: Culturing primary
      hepatocytes within a three-dimensional (3D) structure that mimics the natural
      liver environment is a promising strategy for extending the function and
      viability of hepatocytes in vitro. In the present study we generate porous PLGA
      nanofibers, that are chemically modified with extracellular matrix proteins, to
      serve as 3D scaffolds for the in vitro culture of primary human hepatocytes. Our
      findings demonstrate that the use of ECM proteins, especially type I collagen, in
      a porous 3D environment helps to improve the synthetic function of primary
      hepatocytes over time. We believe the work presented within will provide insights
      to readers for drug toxicity and tissue engineering applications.

PMID- 29454158
TI  - Polyisocyanopeptide hydrogels: A novel thermo-responsive hydrogel supporting pre
      vascularization and the development of organotypic structures.
AB  - : Molecular and mechanical interactions with the 3D extracellular matrix are
      essential for cell functions such as survival, proliferation, migration, and
      differentiation. Thermo-responsive biomimetic polyisocyanopeptide (PIC) hydrogels
      are promising new candidates for 3D cell, tissue, and organ cultures. This is a
      synthetic, thermo-responsive and stress-stiffening material synthesized via
      polymerization of the corresponding monomers using a nickel perchlorate as a
      catalyst. It can be tailored to meet various demands of cells by modulating its
      stiffness and through the decoration of the polymer with short GRGDS peptides
      using copper free click chemistry. These peptides make the hydrogels
      biocompatible by mimicking the binding sites of certain integrins. This study
      focuses on the optimization of the PIC polymer properties for efficient cell,
      tissue and organ development. Screening for the optimal stiffness of the hydrogel
      and the ideal concentration of the GRGDS ligand conjugated with the polymer,
      enabled cell proliferation, migration and differentiation of various primary cell
      types of human origin. We demonstrate that fibroblasts, endothelial cells,
      adipose-derived stem cells and melanoma cells, do survive, thrive and
      differentiate in optimized PIC hydrogels. Importantly, these hydrogels support
      the spontaneous formation of complex structures like blood capillaries in vitro.
      Additionally, we utilized the thermo-responsive properties of the hydrogels for a
      rapid and gentle recovery of viable cells. Finally, we show that organotypic
      structures of human origin grown in PIC hydrogels can be successfully
      transplanted subcutaneously onto immune-compromised rats, on which they survive
      and integrate into the surrounding tissue. STATEMENT OF SIGNIFICANCE: Molecular
      and mechanical interactions with the surrounding environment are essential for
      cell functions. Although 2D culture systems greatly contributed to our
      understanding of complex biological phenomena, they cannot substitute for crucial
      interaction that take place in 3D. 3D culture systems aim to overcome limitations
      of the 2D cultures and answer new questions about cell functions. Thermo
      responsive biomimetic polyisocyanopeptide (PIC) hydrogels are promising new
      candidates for 3D cell, tissue, and organ cultures. They are synthetic and can be
      tailor to meet certain experimental demands. Additionally, they are characterized
      by strain-stiffening, a feature crucial for cell behaviour, but rare in
      hydrogels. Their thermos-responsive properties enable quick recovery of the cells
      by a simple procedure of lowering the temperature.

PMID- 29454159
TI  - An aligned porous electrospun fibrous membrane with controlled drug delivery - An
      efficient strategy to accelerate diabetic wound healing with improved
      angiogenesis.
AB  - : A chronic wound in diabetic patients is usually characterized by poor
      angiogenesis and delayed wound closure. The exploration of efficient strategy to
      significantly improve angiogenesis in the diabetic wound bed and thereby
      accelerate wound healing is still a significant challenge. Herein, we reported a
      kind of aligned porous poly (l-lactic acid) (PlLA) electrospun fibrous membranes
      containing dimethyloxalylglycine (DMOG)-loaded mesoporous silica nanoparticles
      (DS) for diabetic wound healing. The PlLA electrospun fibers aligned in a single
      direction and there were ellipse-shaped nano-pores in situ generated onto the
      surface of fibers, while the DS were well distributed in the fibers and the DMOG
      as well as Si ion could be controlled released from the nanopores on the fibers.
      The in vitro results revealed that the aligned porous composite membranes (DS-PL)
      could stimulate the proliferation, migration and angiogenesis-related gene
      expression of human umbilical vein endothelial cells (HUVECs) compared with the
      pure PlLA membranes. The in vivo study further demonstrated that the prepared DS
      PL membranes significantly improved neo-vascularization, re-epithelialization and
      collagen formation as well as inhibited inflammatory reaction in the diabetic
      wound bed, which eventually stimulated the healing of the diabetic wound.
      Collectively, these results suggest that the combination of hierarchical
      structures (nanopores on the aligned fibers) with the controllable released DMOG
      drugs as well as Si ions from the membranes, which could create a synergetic
      effect on the rapid stimulation of angiogenesis in the diabetic wound bed, is a
      potential novel therapeutic strategy for highly efficient diabetic wound healing.
      STATEMENT OF SIGNIFICANCE: A chronic wound in diabetic patients is usually
      characterized by the poor angiogenesis and the delayed wound closure. The main
      innovation of this study is to design a new kind of skin tissue engineered
      scaffold, aligned porous poly (l-lactic acid) (PlLA) electrospun membranes
      containing dimethyloxalylglycine (DMOG)-loaded mesoporous silica nanoparticles
      (DS), which could significantly improve angiogenesis in the diabetic wound bed
      and thereby accelerate diabetic wound healing. The results revealed that the
      electrospun fibers with ellipse-shaped nano-pores on the surface were aligned in
      a single direction, while there were DS particles distributed in the fibers and
      the DMOG as well as Si ions could be controllably released from the nanopores on
      the fibers. The in vitro studies demonstrated that the hierarchical
      nanostructures (nanopores on the aligned fibers) and the controllable released
      chemical active agents (DMOG drugs and Si ions) from the DS-PL membranes could
      exert a synergistic effect on inducing the endothelial cell proliferation,
      migration and differentiation. Above all, the scaffolds distinctly induced the
      angiogenesis, collagen deposition and re-epithelialization as well as inhibited
      inflammation reaction in the wound sites, which eventually stimulated the healing
      of diabetic wounds in vivo. The significance of the current study is that the
      combination of the hierarchical aligned porous nanofibrous structure with DMOG
      loaded MSNs incorporated in electrospun fibers may suggest a high-efficiency
      strategy for chronic wound healing.

PMID- 29454160
TI  - Vascular parameters continue to decrease post-exposure with simultaneous, but not
      individual exposure to BPA and hypoxia in zebrafish larvae.
AB  - How fish respond to hypoxia, a common stressor, can be altered by simultaneous
      exposure to pollutants like bisphenol A (BPA), a plasticizer. BPA is cardiotoxic
      and interferes with the hypoxia inducible factor pathway (HIF-1alpha), therefore
      disrupting the hypoxic response. Co-exposure to hypoxia and BPA also causes
      severe bradycardia and reduced cardiac output in zebrafish larvae. The purpose of
      this work was to determine how the cardiovascular effects of co-exposure vary
      with BPA concentration and persist beyond exposure. Zebrafish embryos were
      exposed to 0, 0.01, 0.1, 1, and 100 MUg/L of BPA during normoxia (>6.0 mg/L O2)
      and hypoxia (2.0 +/- 0.5 mg/L O2) between 1 h post fertilization (hpf) and late
      hatching (72-96 hpf). Heart rate, cardiac output, and red blood cell (RBC)
      velocity were determined through video microscopy and digital motion analysis at
      late hatching and 10 days post fertilization (dpf), several days post exposure.
      In comparison to the hypoxic control, RBC velocity was 25% lower with 0.01 MUg/L
      BPA and hypoxia at late hatching. At 10 dpf, the difference in RBC velocity
      between these treatments doubled, despite several days of recovery. This
      coincided with a 24% thinner outer diameter for caudal vein but no effect on
      cardiac or developmental parameters. Statistical interactions between BPA and
      oxygen concentration were found for arterial RBC velocity at both ages. Because
      the co-occurrence of both stressors is extremely common, it would be beneficial
      to understand how BPA and hypoxia interact to affect cardiovascular function
      during and after exposure.

PMID- 29454161
TI  - Physiological low-dose oestrogen promotes the development of experimental
      autoimmune thyroiditis through the up-regulation of Th1/Th17 responses.
AB  - Previous studies have reported a preponderance of autoimmune thyroiditis (AIT) in
      females, but the detailed mechanisms have not been elucidated. In this study, we
      explored the effects of oestrogen on experimental AIT (EAT) and its potential
      mechanisms in an ovariectomised mouse model through the supplementation of high
      (equivalent to the level during pregnancy) or low (equivalent to the level at the
      oestrus stage) doses of oestradiol (E2). We found that EAT incidence, the
      intrathyroidal inflammatory score, serum anti-thyroglobulin IgG2b levels, splenic
      mRNA expression of Th1- and Th17-specific transcription factors and typical
      cytokines and the proportion of IL-12-producing dendritic cells were
      significantly increased in EAT mice treated with low-dose E2 compared with those
      in the control group. However, they were not changed when administered with high
      dose E2. These findings indicate that low physiological levels of E2 can
      stimulate the occurrence and development of EAT through the up-regulation of
      Th1/Th17 responses.

PMID- 29454163
TI  - Exacerbations in Adults with Asthma: A Systematic Review and External Validation
      of Prediction Models.
AB  - BACKGROUND: Several prediction models assessing future risk of exacerbations in
      adult patients with asthma have been published. Applicability of these models is
      uncertain because their predictive performance has often not been assessed beyond
      the population in which they were derived. OBJECTIVE: This study aimed to
      identify and critically appraise prediction models for asthma exacerbations and
      validate them in 2 clinically distinct populations. METHODS: PubMed and EMBASE
      were searched to April 2017 for reports describing adult asthma populations in
      which multivariable models were constructed to predict exacerbations during any
      time frame. After critical appraisal, the models' predictive performances were
      assessed in a primary and a secondary care population for author-defined
      exacerbations and for American Thoracic Society/European Respiratory Society
      defined severe exacerbations. RESULTS: We found 12 reports from which 24
      prediction models were evaluated. Three predictors (previous health care
      utilization, symptoms, and spirometry values) were retained in most models.
      Assessment was hampered by suboptimal methodology and reporting, and by
      differences in exacerbation outcomes. Discrimination (area under the receiver
      operating characteristic curve [c-statistic]) of models for author-defined
      exacerbations was better in the primary care population (mean, 0.71) than in the
      secondary care population (mean, 0.60) and similar (0.65 and 0.62, respectively)
      for American Thoracic Society/European Respiratory Society-defined severe
      exacerbations. Model calibration was generally poor, but consistent between the 2
      populations. CONCLUSIONS: The preservation of 3 predictors in models derived from
      variable populations and the fairly consistent predictive properties of most
      models in 2 distinct validation populations suggest the feasibility of a
      generalizable model predicting severe exacerbations. Nevertheless, improvement of
      the models is warranted because predictive performances are below the desired
      level.

PMID- 29454164
TI  - Self-reported inhibition predicts history of suicide attempts in bipolar disorder
      and major depression.
AB  - BACKGROUND: Studies have reliably identified an association between suicide
      attempts and executive functions such as decision making (DM) and inhibitory
      control (IC) in patients with mood disorders. As such, the present study aimed to
      investigate the association between inhibition, DM, impulsivity and the history
      of suicide attempts in individuals with bipolar (BD) or major depressive disorder
      (MDD), identifying which assessment instruments may be most strongly associated
      with suicide in clinical samples. METHODS: The sample included 80 control
      subjects and two groups of patients with BD and MDD, matched by age and education
      (26 with a history of suicide attempts [MD+], and 26 with no such history [MD-]).
      Participants completed behavioral and self-report measures of DM and IC, which
      were compared between groups using ANCOVA, followed by logistic regression for
      patients with mood disorders only, and the presence or absence of a history of
      suicide as the outcome. RESULTS: Cognitive performance did not differ between
      groups. The MD+ group showed significantly higher motor and attentional
      impulsivity on the BIS-11 than the MD- and control groups. A regression analysis
      containing these scores showed that motor impulsivity was the only significant
      predictor of a history of suicide (OR = 1.14; 95%CI 1.00-1.30). CONCLUSIONS: Self
      reported motor impulsivity was a significant predictor of suicide. These findings
      underscore the importance of self-report measures in neuropsychological
      assessment, and their contributions to the management and prognosis of patients
      with mood disorders. Lastly, they point to the role of impulsivity as a target
      for interventions and public policy on suicide prevention.

PMID- 29454165
TI  - Pituitary gland shrinkage in bipolar disorder: The role of gender.
AB  - BACKGROUND: Hyperactivity of the Hypothalamic-Pituitary-Adrenal Axis (HPAA) has
      been consistently reported in mood disorders. However, only few studies
      investigated the Pituitary gland (PG) in Bipolar Disorder (BD) and the results
      are so far contrasting. Therefore, the aim of this study is to explore the
      integrity of the PG as well as the role of gender and the impact of clinical
      measurements on this structure in a sample of BD patients compared to healthy
      controls (HC). METHODS: 34 BD patients and 41 HC underwent a 1.5 T MRI scan. PG
      volumes were manually traced for all subjects. Psychiatric symptoms were assessed
      by means of the Brief Psychiatry Rating Scale, the Hamilton Depression Rating
      Scale and the Bech Rafaelsen Mania Rating Scale. RESULTS: We found decreased PG
      volumes in BD patients compared to HC (F = 24.9, p < 0.001). Interestingly, after
      dividing the sample by gender, a significant PG volume decrease was detected only
      in female BD patients compared to female HC (F = 9.1, p < 0.001), but not in male
      BD compared to male HC (F = -0.12, p = 0.074). No significant correlations were
      observed between PG volumes and clinical variables. CONCLUSIONS: Our findings
      suggest that BD patients have decreased PG volumes, probably due to the long-term
      hyperactivity of the HPAA and to the consequent strengthening of the negative
      feedback control towards the PG volume itself. This alteration was particularly
      evident in females, suggesting a role of gender in affecting PG volumes in BD.
      Finally, the absence of significant correlations between PG volumes and clinical
      variables further supports that PG disruption is a trait feature of BD, being
      independent of symptoms severity and duration of treatment.

PMID- 29454166
TI  - A water-based topical Chinese traditional medicine (Zicao) for wound healing
      developed using 2-hydroxypropyl-beta-cyclodextrin.
AB  - Zicao is a traditional Chinese herbal medicine that has been used for the topical
      treatment of wounds in the form of oil-based ointment for several hundred years.
      To overcome the disadvantages of oil-based ointment such as irritation,
      discomfort, and difficulty in cleaning, this study developed a water-based
      topical formulation of Zicao. An ethanol extract of Zicao was included in 2
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) to form a water-soluble Zicao-HP
      beta-CD complex. The formation of the Zicao-HP-beta-CD complex was determined
      using LC-MS, 1H NMR, ROSEY, and solubility analysis. The bioactivity of Zicao-HP
      beta-CD complex in aqueous solution was evaluated using cellular uptake in vitro
      and experimental excision wounds in vivo. The LC-MS, 1H NMR, ROESY, and
      solubility analyses results show that Zicao extract was successfully included by
      the HP-beta-CD. The results of the cellular uptake in vitro and wound healing in
      vivo suggest that the effect of Zicao was enhanced following the formation of the
      Zicao-HP-beta-CD complex. Therefore, we concluded that complexation with HP-beta
      CD might provide a potential method for developing an effective water-based
      topical solution of Zicao.

PMID- 29454162
TI  - Anxiety, Depression, and Asthma Control: Changes After Standardized Treatment.
AB  - BACKGROUND: It has been documented that anxiety and depression are prevalent in
      patients with asthma and are associated with greater frequency of exacerbations,
      increased use of health care resources, and poor asthma control. OBJECTIVE: To
      examine the association of asthma diagnosis with symptoms of depression/anxiety
      and asthma control not only at baseline but also over a 6-month period of
      specialist supervision. METHODS: We enrolled 3182 patients with moderate to
      severe asthma. All were evaluated with spirometry, the Asthma Control Test, and
      the Hospital Anxiety and Depression Scale at baseline and at 6 months. Treatments
      were decided by specialists according to published guidelines. RESULTS: At
      baseline, 24.2% and 12% of the patients were diagnosed with anxiety and
      depression, respectively, according to the Hospital Anxiety and Depression Scale.
      After 6 months, anxiety and depression improved, affecting 15.3% and 8.1% of
      patients, respectively (P < .001); mean FEV1 and asthma control also improved
      (FEV1 from 81.6% +/- 20.9% to 86% +/- 20.8%; Asthma Control Test score from 15.8
      +/- 4.7 to 19.4 +/- 4.4; both P < .001). Patients with anxiety and depression
      used significantly more health care resources and had more exacerbations. A
      multivariate analysis showed that patients with anxiety, depression, and lower
      FEV1 (odds ratio, 0.20, 0.34, 0.62, respectively; P < .001) were independently
      associated with poor asthma control. A multiple linear regression analysis showed
      that anxiety had a nearly 4-fold greater influence over asthma control than
      depression (0.326/0.85 = 4.075). CONCLUSION: Under standardized asthma care and
      after a specific visit with the specialist, patients present significant
      improvement in these psychological disorders and exhibit better asthma control
      and functional parameters.

PMID- 29454167
TI  - Polydopamine-coated nanocomposites of Angelica gigas Nakai extract and their
      therapeutic potential for triple-negative breast cancer cells.
AB  - Polydopamine (PD)-coated nanocomposites (NCs) based on the ethanol extract of
      Angelica gigas Nakai (AGN EtOH ext) were fabricated and evaluated for breast
      cancer therapy. AGN NCs were prepared using a modified emulsification-solvent
      evaporation method and were further incubated in dopamine solution (at pH 8.6) to
      be covered with the PD layer. PD-AGN NCs with a 213-nm mean diameter, narrow size
      distribution, and negative zeta potential values were fabricated in this study.
      Less negative (close to zero) zeta potential value of PD-AGN NCs than that of AGN
      NCs implied the existence of the PD layer in the outer surface of NCs. The PD
      layer in PD-AGN NCs was also identified by X-ray photoelectron spectroscopy (XPS)
      and ultraviolet (UV)/visible absorption analyses. The sustained release of
      decursin (D) and decursinol angelate (DA), as major active pharmacological
      components of AGN, was observed in both AGN NCs and PD-AGN NCs. Enhanced cellular
      binding property of PD-AGN NCs, compared to AGN NCs, in MDA-MB-231 (human breast
      adenocarcinoma; triple-negative breast cancer) cells was observed. Improved
      anticancer activities of PD-AGN NCs compared with those of AGN EtOH ext and AGN
      NCs were also shown in MDA-MB-231 cells. The developed PD-AGN NCs may be used as
      remarkable platform nanocarriers for efficient breast cancer therapy.

PMID- 29454168
TI  - Genetic and environmental influences on pubertal hormones in human hair across
      development.
AB  - Puberty is a complex biopsychosocial process that can affect an array of
      psychiatric and medical disorders emerging in adolescence. Although the pubertal
      process is driven by neuroendocrine changes, few quantitative genetic studies
      have directly measured puberty-relevant hormones. Hair samples can now be assayed
      for accumulation of hormones over several months. In contrast to more
      conventional salivary measures, hair measures are not confounded by diurnal
      variation or hormonal reactivity. In an ethnically and socioeconomically diverse
      sample of 1286 child and adolescent twins and multiples from 672 unique families,
      we estimated genetic and environmental influences on hair concentrations of
      testosterone, DHEA, and progesterone across the period of 8-18 years of age. On
      average, male DHEA and testosterone were highly heritable, whereas female DHEA,
      progesterone, and puberty were largely influenced by environmental components. We
      identified sex-specific developmental windows of maximal heritability in each
      hormone. Peak heritability for DHEA occurred at approximately 10 years of age for
      males and females. Peak heritability for testosterone occurred at age 12.5 and
      15.2 years for males and females, respectively. Peak heritability for male
      progesterone occurred at 11.2 years, while the heritability of female
      progesterone remained uniformly low. The identification of specific developmental
      windows when genetic signals for hormones are maximized has critical implications
      for well-informed models of hormone-behavior associations in childhood and
      adolescence.

PMID- 29454169
TI  - Farmyard manure alone and combined with immobilizing amendments reduced cadmium
      accumulation in wheat and rice grains grown in field irrigated with raw
      effluents.
AB  - Cadmium (Cd) stress is a serious concern in agricultural soils worldwide whereas
      little is known about the impact of farmyard manure (FYM) alone or combined with
      limestone, lignite and biochar on Cd concentrations in plants. Wheat was grown in
      Cd-contaminated field amended with control (T1), FYM @ 0.1% (T2), FYM + limestone
      @ 0.05% each (T3), FYM + lignite @ 0.05% each (T4), FYM + biochar @ 0.05% each
      (T5) and subsequent rice was grown without additional use of amendments. Soil
      application of amendments increased straw and grain yield and thousand grain
      weight being maximum in FYM + limestone treatment. Wheat and rice straw yield
      increased by 19% and 10% in T3 than control respectively. Photosynthetic pigments
      increased with the supply of amendments than control. Amendments decreased Cd
      concentration, total Cd uptake in straw and grains and Cd harvest index of both
      crops and the maximum reduction in these parameters was recorded with where FYM +
      limestone (T3). Cd concentration in wheat and rice straw decreased by 78.5% and
      65% in T3 than control, respectively. The highest benefit to cost ratio was
      obtained in FYM + limestone (T3). Ammonium bicarbonate - diethylenetriamine penta
      acetic acid (AB-DTPA) extractable Cd of the post-harvest soil reduced whereas Cd
      immobilization index and soil pH increased with the supply of all treatments than
      control being maximum in T3. The present study revealed that field management
      with FYM + limestone increased plant yield and reduced Cd concentrations in
      grains.

PMID- 29454170
TI  - Enhanced electrokinetic remediation of polluted soils by anolyte pH conditioning.
AB  - In the treatment of a polluted soil, the pH has a strong impact on the
      development of different physicochemical processes as precipitation/dissolution,
      adsorption/desorption or ionic exchange. In addition, the pH determines the
      chemical speciation of the compounds present in the system and, consequently, it
      conditions the transport processes by which those compounds will move. This
      question has aroused great interest in the development of pH control technologies
      coupled to soil remediation processes. In electrokinetic remediation processes,
      pH has usually been controlled by catholyte pH conditioning with acid solutions,
      applied to cases of heavy metals pollution. However, this method is not effective
      with pollutants that can be dissociated in anionic species. In this context, this
      paper presents a study of the electrokinetic remediation of soils polluted with
      2,4-Dichlorophenoxyacetic acid, a common polar pesticide, enhanced with an
      anolyte pH conditioning strategy. A numerical study is proposed to evaluate the
      effectiveness of the strategy. Several numerical tests have been carried out for
      NaOH solutions with different concentrations as pH conditioning fluid. The
      results show that the anolyte pH conditioning strategy makes it possible to
      control the pH of the soil and, consequently, the chemical speciation of
      pollutant species. Thus, it is possible to achieve an important flux of pesticide
      into the anolyte compartment (electro-migration of anionic species and diffusive
      transport of acid species). This way, it possible to maximise the pesticide
      accumulation in this compartment, allowing a much more effective removal of
      pollutants from the soil than without the anolyte pH conditioning strategy.

PMID- 29454171
TI  - Reactive oxygen and iron species monitoring to investigate the electro-Fenton
      performances. Impact of the electrochemical process on the biodegradability of
      metronidazole and its by-products.
AB  - In this study, the monitoring of reactive oxygen species and the regeneration of
      the ferrous ions catalyst were performed during electro-Fenton (EF) process to
      highlight the influence of operating parameters. The removal of metronidazole
      (MTZ) was implemented in an electrochemical mono-compartment batch reactor under
      various ranges of current densities, initial MTZ and ferrous ions concentrations,
      and pH values. It was found that under 0.07 mA cm-2, 0.1 mM of ferrous ions and
      pH = 3, the efficiency of 100 mg L-1 MTZ degradation and mineralization were 100%
      within 20 min and 40% within 135 min of electrolysis, respectively. The highest
      hydrogen peroxide and hydroxyl radical concentrations, 1.4 mM and 2.28 mM
      respectively, were obtained at 60 min electrolysis at 0.07 mA cm-2. Improvement
      of the biodegradability was reached from 60 min of electrolysis with a BOD5/COD
      ratio above 0.4, which was reinforced by a respirometric study, that supports the
      feasibility of coupling electro-Fenton and biological treatment for the
      metronidazole removal.

PMID- 29454172
TI  - Toxicity of lanthanum oxide nanoparticles to the fungus Moniliella wahieum Y12T
      isolated from biodiesel.
AB  - Moniliella wahieum Y12T, isolated from biodiesel was used as a model organism to
      assess the use of lanthanum oxide (La2O3) (60-80 nm) and silver oxide (AgO) (10
      40 nm) nanoparticles as potential fungal inhibitors. This is the first study to
      investigate the use of nanoscale La2O3 as a eukaryotic bio-inhibitor. The AgO
      nanoparticles were relatively effective at inhibiting the growth of M. wahieum
      Y12T. The half maximal effective concentration (EC50) for AgO was 0.012 mg/mL as
      compared with 4.63 mg/mL of La2O3. Fluorescein diacetate analysis showed that AgO
      nanoparticles significantly reduced metabolic activity in M. wahieum Y12T. The
      results of this study indicated that AgO nanoparticles can be a nonspecific
      inhibitor for the treatment of M. wahieum Y12T, a eukaryotic biodiesel
      contaminant.

PMID- 29454173
TI  - Photo-assisted electrochemical abatement of trifluralin using a cathode
      containing a C60-carbon nanotubes composite.
AB  - This work reports the potential application of modified gas-diffusion electrode
      (GDE) with C60-CNT composite, as a stable and efficient cathode material for
      degradation of trifluralin (TRL) pesticide by photo-assisted electrochemical (PE)
      process. C60-CNT composite was prepared and characterized. Subsequently, a novel
      C60-CNT composite modified GDE cathode was developed and the electrochemical and
      physical characteristics of the modified GDEs were studied. C60-CNT composite/GDE
      showed great efficiencies for electro-generating H2O2, owing to huge surface area
      and high conductivity. Afterwards, a comparative study of TRL oxidation via
      photolysis, anodic oxidation (AO) and PE processes using C60-CNT composite/GDE
      revealed the degradation percentages of 42.2, 48.5 and 93.4%, respectively, after
      180 min of treatment. The TRL degradation followed a pseudo-first-order kinetics,
      being faster in the order: photolysis < AO < PE. The effects of various
      operational conditions were assessed on the degradation of TRL. From the results,
      PE process using C60-CNT composite/GDE exhibited great performance for the
      degradation of TRL (20 mg L-1) under its original pH, Na2SO4 electrolyte
      concentration of 0.05 mol L-1, applied current intensity of 300 mA, and flow rate
      of 12.5 L h-1. TOC results displayed that 92.8% of TRL was mineralized after 8 h
      of PE process. In addition, a plausible pathway for mineralization of TRL was
      proposed according to the identified by-products detected by means of gas
      chromatography-mass spectroscopy (GC-MS), High-performance liquid chromatography
      (HPLC) and ion chromatography analyses.

PMID- 29454174
TI  - Mastectomy patterns, but not rates, are changing in the treatment of early breast
      cancer. Experience of a single European institution on 2315 consecutive patients.
AB  - BACKGROUND: Recent literature reports that rates of mastectomy are increasing in
      early breast cancer. However, data from European institutions are limited and
      revealed conflicting results. We report on 15-year trends of mastectomy,
      mastectomy plus immediate reconstruction and contralateral prophylactic
      mastectomy (CPM) at an academic institution. METHODS: We identified women
      diagnosed with unilateral early breast cancer at stage 0-IIa, with tumour size <=
      4 cm, between 2002 and 2016. Trends were assessed using the Cochrane-Armitage
      test. Multivariable logistic regression was used to identify factors associated
      with receipt of mastectomy plus immediate reconstruction. RESULTS: A total of
      2315 patients were identified. Of them, 65.7% underwent breast conserving surgery
      (BCS), while 34.3% underwent mastectomy as upfront surgery. Two point four per
      cent also received CPM. Immediate reconstruction was performed in 36.0% of
      patients receiving mastectomy. There was no change in trends of mastectomy over
      the 15 years studied (p = 0.69), as well as in trends of patients undergoing CPM
      (p = 0.44). In contrast, rates of immediate reconstruction rose significantly
      over the study period (from 12.2% in 2002 to 62.7% in 2016, p < 0.0001). Women
      were more likely to receive mastectomy plus immediate reconstruction if they were
      aged 50 years or younger, or had tumours larger than 2 cm, or had non-invasive
      carcinoma. CONCLUSIONS: Our study suggests that rates of both mastectomy and CPM
      in early breast cancer are not increasing, while use of immediate reconstruction
      is on the rise.

PMID- 29454175
TI  - Anticholinergics to treat antipsychotic-induced extrapyramidal symptoms: Time to
      avoid this practice.

PMID- 29454176
TI  - Efficacy of intensive voice feminisation therapy in a transgender young offender.
AB  - Research suggests that transgender young offenders are a uniquely vulnerable
      caseload that may benefit from speech pathology intervention to help bring their
      voice into alignment with their gender identity. However, no previous studies
      have investigated treatment efficacy in this population. This study investigated
      the impact of intensive voice feminisation therapy targeting fundamental
      frequency and oral resonance in a 17 year old transgender individual within a
      youth justice institution. Acoustic analysis, listener and self-ratings of vocal
      femininity, self-ratings of vocal satisfaction, a post-treatment structured
      interview, and pre- and post- treatment completion of the Transsexual Voice
      Questionnaire (TVQMtF) were utilised to determine treatment impact. Outcome
      measures indicated therapy was effective at increasing the client's vocal pitch
      and perceptually femininity without compromising vocal quality. However, the
      client was still not consistently perceived as female post-intervention and had
      difficulty implementing feminine speech strategies in discourse. This case study
      provides preliminary evidence for the effectiveness of intensive voice
      feminisation therapy in a youth offending population. This research also
      highlights the potential utility of speech pathologists working in youth justice
      settings, even when the timeframe for intervention is limited. Furthermore, this
      research paper validates the use of perceptual outcome measures in transgender
      voice work, by replicating previous findings in which significant correlations
      were found between perceptual ratings of vocal gender and client satisfaction.

PMID- 29454178
TI  - Caffeine use disorder: An item-response theory analysis of proposed DSM-5
      criteria.
AB  - INTRODUCTION: Caffeine is a common psychoactive substance with a documented
      addictive potential. Caffeine withdrawal has been included in the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-5), but caffeine use disorder (CUD)
      is considered to be a condition for further study. The aim of the current study
      is (1) to test the psychometric properties of the Caffeine Use Disorder
      Questionnaire (CUDQ) by using a confirmatory factor analysis and an item response
      theory (IRT) approach, (2) to compare IRT models with varying numbers of
      parameters and models with or without caffeine consumption criteria, and (3) to
      examine if the total daily caffeine consumption and the use of different
      caffeinated products can predict the magnitude of CUD symptomatology. METHODS: A
      cross-sectional study was conducted on an adult sample (N = 2259). Participants
      answered several questions regarding their caffeine consumption habits and
      completed the CUDQ, which incorporates the nine proposed criteria of the DSM-5 as
      well as one additional item regarding the suffering caused by the symptoms.
      RESULTS: Factor analyses demonstrated the unidimensionality of the CUDQ. The
      suffering criterion had the highest discriminative value at a higher degree of
      latent trait. The criterion of failure to fulfill obligations and
      social/interpersonal problems discriminate only at the higher value of CUD latent
      factor, while endorsement the consumption of more caffeine or longer than
      intended and craving criteria were discriminative at a lower level of CUD. Total
      daily caffeine intake was related to a higher level of CUD. Daily coffee, energy
      drink, and cola intake as dummy variables were associated with the presence of
      more CUD symptoms, while daily tea consumption as a dummy variable was related to
      less CUD symptoms. Regular smoking was associated with more CUD symptoms, which
      was explained by a larger caffeine consumption. CONCLUSIONS: The IRT approach
      helped to determine which CUD symptoms indicate more severity and have a greater
      discriminative value. The level of CUD is influenced by the type and quantity of
      caffeine consumption.

PMID- 29454177
TI  - Tobacco harm perceptions and use among sexual and gender minorities: findings
      from a national sample of young adults in the United States.
AB  - INTRODUCTION: In the United States, the prevalence of tobacco use among sexual
      and gender minorities (SGM) is higher compared to their non-SGM counterparts.
      Tobacco harm perceptions have gone largely unexamined as a potential mechanism
      supporting disproportionate tobacco use among this population. The purpose of
      this study was to examine differences between SGM and non-SGM young adults in
      harm perceptions of various tobacco products and tobacco use behavior and whether
      low tobacco-related harm perceptions moderate the relationship between
      identifying as a SGM and tobacco use behavior. METHODS: This study used data from
      Wave 10 of the Truth Initiative Young Adult Cohort Study, a sample of U.S. young
      adults (ages 18-34). Data were collected from September to October 2016 and the
      study sample included 3089 individuals. Demographics, past 30-day use of
      cigarettes, little cigars/cigarillos/bidis and electronic cigarettes were
      assessed. Absolute and relative harm perceptions of these products were also
      examined. RESULTS: Identifying as a SGM and low tobacco harm perceptions were
      found to be positively associated with past 30-day tobacco use. There was no
      interaction between SGM status and harm perceptions on past 30-day tobacco use
      CONCLUSIONS: Findings confirm that SGM young adults continue to
      disproportionately use tobacco products, compared to non-SGM young adults. More
      research is needed to understand moderators of the relationship between SGM
      status and tobacco use in young adults.

PMID- 29454179
TI  - Race/ethnicity and racial group composition moderate the effectiveness of
      mindfulness-based relapse prevention for substance use disorder.
AB  - INTRODUCTION: Mindfulness-based relapse prevention has shown promise as a
      treatment for substance use disorder but its efficacy according to racial/ethnic
      minority status and group composition is unknown. METHOD: This is a secondary
      analysis of existing data (Bowen et al., 2014) testing individual race/ethnicity
      and racial/ethnic group composition as moderators of mindfulness-based relapse
      prevention (MBRP). Participants (N = 191; 29% female; 47% racial/ethnic minority;
      mean age = 39) with substance use disorder were randomized to MBRP or relapse
      prevention (RP). Outcomes were heavy drinking days (HDD) and drug use days (DUD)
      12 months after treatment completion. Negative binominal regression models were
      conducted. RESULTS: Analyses accounted for drug of choice. Individual
      race/ethnicity was a significant moderator of substance use outcomes. White
      participants had lower HDD in MBRP than RP (IRR = 0, 95% CI: 0,0), whereas for
      minority participants, there was no treatment difference in HDD. Conversely,
      minorities had lower DUD in MBRP than RP (IRR = 0.03, 95% CI: 0.01, 0.10),
      whereas for whites there was no treatment difference in DUD. Group racial/ethnic
      composition was a significant moderator. Participants in groups with more than
      half whites had lower HDD in MBRP than RP (IRR = 0.01, 95% CI: 0, 0.09), whereas
      for participants in groups with more than half minorities there was no treatment
      difference in HDD. Exploratory analyses suggested MBRP resulted in better
      outcomes than RP when individual race/ethnic status was reflected in the group
      race/ethnicity (i.e., whites in groups with more than half whites or minorities
      in groups with more than half minorities). CONCLUSIONS: Among whites, MBRP
      appears to be more effective than RP in preventing heavy drinking relapse.
      However, among racial/ethnic minorities, MBRP appears to more effective than RP
      in preventing drug use relapse. This suggests that the interaction between
      individual race/ethnicity and group composition may influence primary outcomes.

PMID- 29454181
TI  - Brainstem dysfunction heralding disseminated cryptococcosis.
AB  - Cryptococcal meningoencephalitis is one of the most common central nervous system
      infections affecting immunocompromised patients. However, brainstem involvement
      is extremely rare and may represent a diagnostic challenge to clinicians. We
      report a non-HIV infected, chronically immunosuppressed, patient with fatal
      disseminated cryptococcosis presented with subcutaneous masses at both thighs and
      progressive brainstem dysfunction. Magnetic resonance imaging demonstrated
      multiple brainstem infarcts likely derived from small vessel vasculopathy. Anti
      fungal treatment led to partial neurologic improvement but the patient succumbed
      to a fatal sepsis from hospital-acquired pneumonia.

PMID- 29454182
TI  - The positive effect of venlafaxine on central motor conduction.
AB  - OBJECTIVES: Using the triple stimulation technique (TST) and conventional
      transcranial magnetic stimulation (TMS), this study was designed to investigate
      the effect of venlafaxine on central motor conduction in healthy adults. PATIENTS
      AND METHODS: In this crossover, self-controlled trial, eight healthy adult
      volunteers were randomly divided into groups A and B. In group A, the volunteers
      were administered 1 venlafaxine capsule once daily for 7 consecutive days,
      followed by a 3-day break. Next, volunteers in this group received 1 placebo
      capsule once daily for 7 consecutive days. Group B received the treatments in the
      opposite order. The index finger tapping test, grip strength test, TST and
      conventional TMS examination for each hand were recorded before and one week
      after the administration of venlafaxine or placebo. RESULTS: Compared to the
      placebo stage, in the venlafaxine stage, the number of index finger taps was
      significantly increased for both hands, and the TST amplitude and area ratios
      were significantly increased. The improvement in the TST amplitude ratio was
      significantly and positively correlated with the improvements in performance on
      the index finger tapping test. CONCLUSION: Venlafaxine positively regulates
      central motor conduction in healthy adults.

PMID- 29454180
TI  - Tryptophan-kynurenine and lipid related metabolites as blood biomarkers for first
      episode drug-naive patients with major depressive disorder: An exploratory pilot
      case-control study.
AB  - BACKGROUND: Early intervention in depression has been critical to prevent its
      negative impact including suicide. Recent blood biomarker studies for major
      depressive disorder (MDD) have suggested that tryptophan-kynurenine and lipid
      related metabolites are involved in the pathophysiology of MDD. However, there
      have been limited studies investigating these blood biomarkers in first-episode
      drug-naive MDD, which are particularly important for early intervention in
      depression. METHODS: As an exploratory pilot case-control study, we examined the
      above blood biomarkers, and analyzed how these biomarkers are associated with
      clinical variables in first-episode drug-naive MDD patients, based on
      metabolome/lipidome analysis. RESULTS: Plasma tryptophan and kynurenine levels
      were significantly lower in MDD group (N = 15) compared to healthy controls (HC)
      group (N = 19), and plasma tryptophan was the significant biomarker to identify
      MDD group (area under the curve = 0.740). Lower serum high density lipoprotein
      cholesterol (HDL-C) was the predictive biomarker for severity of depression in
      MDD group (R2 = 0.444). Interestingly, depressive symptoms were variously
      correlated with plasma tryptophan-kynurenine and lipid related metabolites.
      Moreover, plasma tryptophan-kynurenine metabolites and cholesteryl esters (CEs)
      were significantly correlated in MDD group, but not in HC group. LIMITATIONS:
      This study had small sample size, and we did not use the multiple test
      correction. CONCLUSIONS: This is the first study to suggest that not only
      tryptophan-kynurenine metabolites but also HDL-C and CEs are important blood
      biomarkers for first-episode drug-naive MDD patients. The present study sheds new
      light on early intervention in clinical practice in depression, and further
      clinical studies especially large-scale prospective studies are warranted.

PMID- 29454183
TI  - The fine balance between mutualism and antagonism in the Epichloe festucae-grass
      symbiotic interaction.
AB  - Epichloe endophytes form mutualistic symbiotic associations with aerial tissues
      of temperate grasses. Intercalary growth of hyphae within the leaves enables
      fungal growth to be synchronized with host leaf growth, leading to formation of a
      highly structured and tightly regulated symbiotic network. Mutations in fungal
      genes that disrupt cell-cell fusion and other key signalling pathways lead to an
      antagonistic interaction characterized by unregulated growth of endophytic hyphae
      and detrimental effects on host growth. Transcriptome analysis of these mutant
      associations provides key insights into the regulation of the symbiosis. In
      nature a similar switch in growth occurs when hyphae transition into the sexual
      cycle forming stromata that abort host inflorescences. Endophyte infection of the
      grass host leads to a major reprogramming of host metabolism and alters host
      development. Changes in endophyte cell wall structure and the repertoire of
      effectors secreted into the host apoplast accompany establishment of a
      mutualistic interaction within the leaves.

PMID- 29454184
TI  - Exploration and exploitation of the environment for novel specialized
      metabolites.
AB  - Microorganisms are Nature's little engineers of a remarkable array of bioactive
      small molecules that represent most of our new drugs. The wealth of genomic and
      metagenomic sequence data generated in the last decade has shown that the
      majority of novel biosynthetic gene clusters (BGCs) is identified from
      cultivation-independent studies, which has led to a strong expansion of the
      number of microbial taxa known to harbour BGCs. The large size and repeat
      sequences of BGCs remain a bioinformatic challenge, but newly developed software
      tools have been created to overcome these issues and are paramount to identify
      and select the most promising BGCs for further research and exploitation.
      Although heterologous expression of BGCs has been the greatest challenge until
      now, a growing number of polyketide synthase (PKS) and non-ribosomal peptide
      synthetase (NRPS)-encoding gene clusters have been cloned and expressed in
      bacteria and fungi based on techniques that mostly rely on homologous
      recombination. Finally, combining ecological insights with state-of-the-art
      computation and molecular methodologies will allow for further comprehension and
      exploitation of microbial specialized metabolites.

PMID- 29454185
TI  - Preterm infants undergoing laparotomy for necrotizing enterocolitis or
      spontaneous intestinal perforation display evidence of impaired cerebrovascular
      autoregulation.
AB  - BACKGROUND: Preterm infants requiring surgery are at risk of impaired
      neurocognitive development caused, possibly, by cerebral ischemia associated with
      impaired cerebrovascular autoregulation (CAR). We evaluated CAR before, during,
      and after laparotomy. STUDY DESIGN: This was a hypothesis generating prospective
      observational cohort study. SUBJECTS: We included preterm infants requiring
      surgery for necrotizing enterocolitis (NEC) or spontaneous intestinal perforation
      (SIP). Before, during, and after surgery we measured cerebral oxygen saturation
      using NIRS and calculated cerebral fractional tissue oxygen extraction (cFTOE).
      OUTCOME MEASURES: Impaired CAR was defined if correlation coefficients (rho)
      between mean cFTOE and mean arterial blood pressure values were <=-0.30 with P <
      .05. We used logistic regression analyses to determine factors associated with
      impaired CAR. RESULTS: Nineteen infants with median (IQR) GA 27.6 weeks (26.6
      31.0), birth weight 1090 g (924-1430), and postnatal age 9 days (7-12) were
      included. CAR was impaired more often during surgery than before (12 versus 3, P
      = .02) or after (12 versus 0, P < .01). A higher PCO2 level was associated with
      impaired CAR during surgery (OR 3.04, 95% CI, 1.11-8.12 for every 1 kPa
      increase). CONCLUSIONS: More than half of preterm infants with NEC or SIP
      displayed evidence of impaired CAR during laparotomy. Further research should
      focus on mechanisms contributing to impaired CAR in preterm infants during
      surgery.

PMID- 29454186
TI  - Use of pasteurised human donor milk across neonatal networks in England.
AB  - OBJECTIVES: To describe the use of pasteurised human donor milk (pHDM) in England
      and the influence of a human milk bank in the network. DESIGN: Prospective
      observational study SETTING: All 163 neonatal units (23 networks) in England 2012
      2013. PATIENTS: Preterm infants born at <32 weeks gestational age (GA). MAIN
      OUTCOME MEASURES: Proportion of infants and care-days fed pHDM during the first
      30 postnatal days by network METHODS: We extracted daily patient-level data from
      the National Neonatal Research Database (NNRD). We fitted a logistic regression
      of pHDM exposure on the presence of a pHDM bank within the network, with GA, BW z
      score and network as covariates. Significance was assessed by the likelihood
      ratio (chi-squared) test. RESULTS: Data for 13,463 infants were included in the
      study. Across the networks, the proportion (95%CI) of infants ranged from 2.0%
      (1.0, 3.0) to 61.0% (57.4%, 64.6%), and the proportion of care-days in which pHDM
      was fed from 0.08% (0.04%, 0.10%) to 21.9% (19.9%, 24.0%). In three networks <5%,
      and in seven networks >30% of infants received any pHDM. Variation in the use of
      pHDM across networks remained significant after adjustment for presence of a
      human milk bank within the network and all covariates (p < 0.001). CONCLUSIONS:
      Wide variation of pHDM use in England is not fully explained by presence of a
      pHDM bank or patient characteristics. This suggests clinical uncertainty about
      the use of pHDM.

PMID- 29454187
TI  - Investigating the time-dependent zeta potential of wood surfaces.
AB  - This work reports on streaming potential measurements through natural capillaries
      in wood and investigates the cause of a time-dependent zeta potential measured
      during the equilibration of wood cell-walls with an electrolyte solution. For the
      biomaterial, this equilibration phase takes several hours, which is much longer
      than for many other materials that have been characterized by electrokinetic
      measurements. During this equilibration phase the zeta potential magnitude is
      decaying due to two parallel mechanisms: (i) the swelling of the cell-wall which
      causes a dimensional change reducing the charge density at the capillary
      interface; (ii) the transport of ions from the electrolyte solution into the
      permeable cell-wall which alters the electrical potential at the interface by
      internal charge compensation. The obtained results demonstrate the importance of
      equilibration kinetics for an accurate determination of the zeta potential,
      especially for materials that interact strongly with the measurement electrolyte.
      Moreover, the change in zeta potential with time can be correlated with the bulk
      swelling of wood if the effect of electrolyte ion diffusion is excluded. This
      study shows the potential of streaming potential measurements of wood, and
      possibly of other hygroscopic and nanoporous materials, to reveal kinetic
      information about their interaction with liquids, such as swelling and ion
      uptake.

PMID- 29454189
TI  - Pyrimidine-chloroquinoline hybrids: Synthesis and antiplasmodial activity.
AB  - Triazole tethered 7-chloroquinoline-pyrimidine-5-carboxylate hybrids were
      synthesized and evaluated for antiplasmodial activity against chloroquine
      sensitive (CQS) NF54 strain of Plasmodium falciparum. The most active hybrids of
      the series were further screened against the chloroquine resistant (CQR) Dd2
      strain of the parasite and for in vitro cytotoxicity against mammalian Vero cell
      lines. Further, their physico-chemical properties, binding studies with hemin
      (monomeric &MU-oxo dimeric) and DNA [pUC-18, calf thymus (CT)] led us to
      plausible proposed binding mode of the most active member of the present series.

PMID- 29454188
TI  - Modified two-step emulsion solvent evaporation technique for fabricating
      biodegradable rod-shaped particles in the submicron size range.
AB  - HYPOTHESIS: Though the emulsion solvent evaporation (ESE) technique has been
      previously modified to produce rod-shaped particles, it cannot generate small
      sized rods for drug delivery applications due to the inherent coupling and
      contradicting requirements for the formation versus stretching of droplets. The
      separation of the droplet formation from the stretching step should enable the
      creation of submicron droplets that are then stretched in the second stage by
      manipulation of the system viscosity along with the surface-active molecule and
      oil-phase solvent. EXPERIMENTS: A two-step ESE protocol is evaluated where oil
      droplets are formed at low viscosity followed by a step increase in the aqueous
      phase viscosity to stretch droplets. Different surface-active molecules and oil
      phase solvents were evaluated to optimize the yield of biodegradable PLGA rods.
      Rods were assessed for drug loading via an imaging agent and vascular-targeted
      delivery application via blood flow adhesion assays. FINDINGS: The two-step ESE
      method generated PLGA rods with major and minor axis down to 3.2 um and 700 nm,
      respectively. Chloroform and sodium metaphosphate was the optimal solvent and
      surface-active molecule, respectively, for submicron rod fabrication. Rods
      demonstrated faster release of Nile Red compared to spheres and successfully
      targeted an inflamed endothelium under shear flow in vitro and in vivo.

PMID- 29454190
TI  - Potholing of the hydrophobic heme oxygenase-1 western region for the search of
      potent and selective imidazole-based inhibitors.
AB  - Here we report the design, synthesis, and molecular modeling of new potent and
      selective imidazole-based HO-1 inhibitors in which the imidazole nucleus and the
      hydrophobic groups are linked by a phenylethanolic spacer. Most of the tested
      compounds showed a good inhibitor activity with IC50 values in the low micromolar
      range, with two of them (1b and 1j) exhibiting also high selectivity toward HO-2.
      These results were obtained by the idea of potholing the entire volume of the
      principal hydrophobic western region with an appropriate ligand volume. Molecular
      modeling studies showed that these molecules bind to the HO-1 in the consolidated
      fashion where the imidazolyl moiety coordinates the heme iron while the aromatic
      groups are stabilized by hydrophobic interaction in the western region of the
      binding pocket. Finally, the synthesized compounds were analyzed for in silico
      ADME-Tox properties to establish oral drug-like behavior and showed satisfactory
      results.

PMID- 29454191
TI  - Show me the way: rust effector targets in heterologous plant systems.
AB  - For years, the study of rust fungal effectors has been impeded by the lack of
      molecular genetic tools in rust pathosystems. The recent use of heterologous
      plants to perform effector screens (effectoromics)-including effector
      localisation (cellular targets) and protein interactors (molecular targets) in
      plant cells-has changed the game. These screens revealed that many candidate
      effectors from various rust fungi target specific plant cell compartments,
      including chloroplasts, and associate with specific plant protein complexes. Such
      information represents unparalleled opportunities to understand how effectors
      sustain extreme parasitic interactions and obligate biotrophy. Despite their
      limitations, we here portray how the use of heterologous expression systems has
      been essential for gaining new insight into rust effectors.

PMID- 29454192
TI  - Phytophthora sojae effectors orchestrate warfare with host immunity.
AB  - Phytophthora sojae is one of the most damaging plant pathogens of soybean. To aid
      establishment of a compatible interaction with its host, P. sojae deploys many
      secreted effectors. These effectors act either in the apoplastic space to cope
      with hostile conditions or inside of host cells to reprogram host physiology
      favoring pathogen growth. Effectors have been used as molecular probes, which
      revealed in Phytophthora that effectors execute their virulence function via
      manipulating host targets. In addition, recent studies have discovered 'pseudo
      effectors' in Phytophthora that act as decoys to shield virulence effectors from
      host defense, a new paradigm in plant-pathogen interactions.

PMID- 29454193
TI  - Revealing metabolic storage processes in electrode respiring bacteria by
      differential electrochemical mass spectrometry.
AB  - In this work we employ differential electrochemical mass spectrometry (DEMS) in
      combination with static and dynamic electrochemical techniques for the study of
      metabolic processes of electrochemically active bacteria. CO2 production during
      acetate oxidation by electrode respiring bacteria was measured, in-vivo and
      online with a sensitivity of 6.5 ? 10-13 mol/s. The correlation of ion current
      and electrical current provides insight into the interaction of metabolic
      processes and extra-cellular electron transfer. In low-turnover CVs, two
      competing potential dependent electron transfer mechanisms were observed and
      formal potentials of two redox systems that are involved in complete oxidation of
      acetate to CO2 were determined. By balancing charge and carbon flows during
      dynamic measurements, two significant storage mechanisms in electrochemically
      active bacteria were identified: 1) a charge storage mechanism that allows
      substrate oxidation to proceed at a constant rate despite of external current
      flowing in cathodic direction. 2) a carbon storage mechanism that allows the
      biofilm to take up acetate at an unchanged rate at very low potentials even
      though the oxidation to CO2 stops. These storage capabilities allow a limited
      decoupling of electrical current and CO2 production rate.

PMID- 29454194
TI  - Diagnostic and treatment services for patients with Psychogenic Nonepileptic
      Seizures (PNES): A survey of health professionals in urban China.
AB  - PURPOSE: This study is intended to provide an overview of diagnostic and
      treatment services for patients with psychogenic nonepileptic seizures (PNES)
      across China. METHODS: Using a questionnaire devised by the PNES Task Force of
      Neuropsychiatry Commission of the International League Against Epilepsy (ILAE),
      we conducted a survey among Chinese health professionals at the Sixth Advanced
      International Course: Clinical Epileptology. Descriptive analyses were performed.
      RESULTS: Responses from 102 eligible clinicians were analysed. Responses were
      received from urban areas in 20 provinces/municipalities around China. Most
      respondents were neurologists. The results showed that hospitals in urban China
      were mostly well-equipped, and that health professionals' understanding of PNES
      largely reflected current international expert opinion. However, many of the
      participants would not actually make the diagnosis, and most provided neither
      follow-up nor treatment (especially psychotherapy) for patients with PNES. Only
      about one third of the patients diagnosed with PNES were estimated to receive at
      least one appointment for psychological treatment. In the opinion of the
      respondents, tacit trauma (neglect and stress) play an important role in the
      development of PNES. The main obstacles to patients with PNES accessing health
      services for their condition were thought to be lack of knowledge or awareness
      among health professionals, patients and society. CONCLUSION: Despite good access
      to equipment, diagnostic and treatment services for patients with PNES in China
      are currently deficient. Education programs about PNES with different target
      groups, and more effective referral and social security systems emerge as
      particular development needs from this survey.

PMID- 29454195
TI  - CHRNA4 variant causes paroxysmal kinesigenic dyskinesia and genetic epilepsy with
      febrile seizures plus?
AB  - PURPOSE: Paroxysmal kinesigenic dyskinesia (PKD) and epilepsy are thought to have
      a shared genetic etiology. PRRT2 has been identified as a causative gene of both
      disorders. In this study, we aim to explore the potential novel causative gene in
      a PRRT2-negative family with three individuals diagnosed with PKD or genetic
      epilepsy with febrile seizures plus (GEFS+). METHODS: Clinical data were
      collected from all the affected and unaffected members of a PKD/GEFS+ family. The
      Brain magnetic resonance imaging and 24 h video-EEG of all three affected members
      were analyzed. Targeted gene-panel sequencing was used to detect the genetic
      defect in genomic DNAs of three affected and five normal individuals. Co
      segregation analysis of putatively pathogenic mutations with the phenotype was
      carried out in all the family members alive to examine the inheritance status.
      RESULTS: The inheritance model of this pedigree was autosomal dominant. A novel,
      fully co-segregated mutation (NM_000744: c.979G > A) in CHRNA4 was identified in
      the family with three individuals diagnosed with PKD or GEFS+. CONCLUSIONS:
      CHRNA4 may be a novel gene causing of PKD and GEFS+. Our study extends the
      genotypic-phenotypic spectrum of combined epileptic and dyskinetic syndromes, and
      provides a genetic linkage between PKD and GEFS+.

PMID- 29454197
TI  - Cigarette butts may have low toxicity to soil-dwelling invertebrates: Evidence
      from a land snail.
AB  - Cigarette butts are a common form of litter that is often deposited on soil,
      where toxins from butts may affect soil-dwelling organisms. We examined possible
      toxicity of cigarette butts to the woodland snail Anguispira alternata using a
      toxicity study with cigarette butt effluent and a lab-based habitat choice
      experiment in which snails could feed or rest on areas with different butt
      densities. No mortality occurred during the 32-day toxicity study, which used six
      effluent concentrations ranging from 0 to 4butts/l (0 to 0.92butts/kg of soil).
      Neither food consumption nor snail growth differed among the effluent
      concentrations. When provided a choice among four habitats with 0 to 4 cigarette
      butts, snails selected to preferentially rest in the 0-butt habitat and avoided
      the 4-butt habitat. This distribution pattern was strong during the first wk. but
      became weaker over time and largely disappeared by the end of the 3-wk
      experiment. Snails did not discriminate among butt densities when feeding. This
      is the first toxicity test using cigarette butts on soil-dwelling invertebrates.
      Declining aversion to cigarette butts over a 3-wk period may indicate declining
      toxicity of terrestrially deposited butts as they age, but further testing is
      needed.

PMID- 29454196
TI  - Sexually transmitted infections and immune activation among HIV-infected but
      virally suppressed youth on antiretroviral therapy.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with
      chronic immune activation, and concurrent sexually transmitted infections (STIs)
      may increase immune activation. OBJECTIVES: Because HIV-infected youth are at
      high risk of STIs and little is known about the impact of STIs on immune
      activation in HIV-infected youth, we conducted an exploratory study examining the
      association between STIs and systemic inflammation and immune activation among
      HIV-infected adolescents. STUDY DESIGN: Forty-nine behaviorally infected U.S.
      youth ages 18-24 years with baseline CD4+ T-cells >350 who maintained viral
      suppression on therapy by week 48 were included. Evaluation for STIs (herpes
      simplex virus [HSV], Chlamydia trachomatis, syphilis, Neisseria gonorrhoeae) was
      conducted as standard of care and reported on case report forms. Measures of T
      cell subsets, systemic immune activation, and soluble factors were examined at
      week 48 for differences between participants with an STI diagnosis during the 48
      weeks compared to those without an STI. RESULTS: Forty-three participants (88%)
      were male; 57% had baseline CD4+ T-cell counts >500 cells/mm3. Eighteen youth
      were reported to have >=1 STI. At week 48, participants with STIs demonstrated
      lower CD4+ T-cell counts (any STI vs. no STI, p = 0.024; HSV vs. no STI, p =
      0.022) and evidence of increased systemic immune activation, including higher
      CD57 intensity, higher HLA-DR intensity, and lower CD28 percentage, when compared
      to those without STIs. There were no differences in soluble factors between STI
      groups. CONCLUSIONS: Results indicate novel activation of CD4+ T-cells among HIV
      infected youth who have STIs other than HSV, which may contribute to disease
      progression.

PMID- 29454198
TI  - Long-term exposure to air pollution and the risk of suicide death: A population
      based cohort study.
AB  - Suicide is a major public health problem. Previous studies have reported a
      significant association between acute exposure to air pollution and suicide;
      little attention has been paid to the long-term effects of air pollution on risk
      of suicide. We investigated whether long-term exposure to particulate matter of
      <=10MUm in diameter (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2)
      would be associated with a greater risk of death by suicide. The study sample
      comprised 265,749 adults enrolled in the National Health Insurance Service
      National Sample Cohort (2002-2013) in South Korea. Suicide death was defined as
      per ICD-10 code. Data on air pollution exposure used nationwide monitoring data,
      and individual exposure levels were assigned using geographic information
      systems. Air pollution exposure was categorized as the interquartile range (IQR)
      and quartiles. Hazards ratios (HRs) were calculated for the occurrence of suicide
      death after adjusting for potential covariates. During the study period, 564
      (0.2%) subjects died from suicide. Increases in IQR pollutants (7.5MUg/m3 for
      PM10, 11.8ppb for NO2, and 0.8ppb for SO2) significantly increased HR for suicide
      death [PM10: HR=3.09 (95% CI: 2.63-3.63); NO2: HR=1.33 (95% CI: 1.09-1.64); and
      SO2: HR=1.15 (95% CI: 1.07-1.24)]. Compared with the lowest level of air
      pollutants (Quartile 1), the risk of suicide significantly increased in the
      highest quartile level (Quartile 4) for PM10 (HR=4.03; 95% CI: 2.97-5.47) and SO2
      (HR=1.65; 95% CI: 1.29-2.11) and in the third quartile for NO2 (HR=1.52; 95% CI:
      1.17-1.96). HRs for subjects with a physical or mental disorder were higher than
      that those for subjects without the disorder. Subjects living in metropolitan
      areas were more vulnerable to long-term PM10 exposure than those living in non
      metropolitan areas. Long-term exposure to air pollution was associated with a
      significantly increased risk of suicide death. People having underlying diseases
      or living in metropolitan areas may be more susceptible to high air pollution
      exposure.

PMID- 29454199
TI  - Benthic nitrite exchanges in the Seine River (France): An early diagenetic
      modeling analysis.
AB  - Nitrite is a toxic intermediate compound in the nitrogen (N) cycle. Elevated
      concentrations of nitrite have been observed in the Seine River, raising
      questions about its sources and fate. Here, we assess the role of bottom
      sediments as potential sources or sinks of nitrite along the river continuum.
      Sediment cores were collected from two depocenters, one located upstream, the
      other downstream, from the largest wastewater treatment plant (WWTP) servicing
      the conurbation of Paris. Pore water profiles of oxygen, nitrate, nitrite and
      ammonium were measured. Ammonium, nitrate and nitrite fluxes across the sediment
      water interface (SWI) were determined in separate core incubation experiments.
      The data were interpreted with a one-dimensional, multi-component reactive
      transport model, which accounts for the production and consumption of nitrite
      through nitrification, denitrification, anammox and dissimilatory nitrate
      reduction to ammonium (DNRA). In all core incubation experiments, nitrate uptake
      by the sediments was observed, indicative of high rates of denitrification. In
      contrast, for both sampling locations, the sediments in cores collected in August
      2012 acted as sinks for nitrite, but those collected in October 2013 released
      nitrite to the overlying water. The model results suggest that the first step of
      nitrification generated most pore water nitrite at the two locations. While
      nitrification was also the main pathway consuming nitrite in the sediments
      upstream of the WWTP, anammox dominated nitrite removal at the downstream site.
      Sensitivity analyses indicated that the magnitude and direction of the benthic
      nitrite fluxes most strongly depend on bottom water oxygenation and the
      deposition flux of labile organic matter.

PMID- 29454200
TI  - Effect of clonal integration on nitrogen cycling in rhizosphere of rhizomatous
      clonal plant, Phyllostachys bissetii, under heterogeneous light.
AB  - Clonal integration plays an important role in clonal plant adapting to
      heterogeneous habitats. It was postulated that clonal integration could exhibit
      positive effects on nitrogen cycling in the rhizosphere of clonal plant subjected
      to heterogeneous light conditions. An in-situ experiment was conducted using
      clonal fragments of Phyllostachys bissetii with two successive ramets. Shading
      treatments were applied to offspring or mother ramets, respectively, whereas
      counterparts were treated to full sunlight. Rhizomes between two successive
      ramets were either severed or connected. Extracellular enzyme activities and
      nitrogen turnover were measured, as well as soil properties. Abundance of
      functional genes (archaeal or bacterial amoA, nifH) in the rhizosphere of shaded,
      offspring or mother ramets were determined using quantitative polymerase chain
      reaction. Carbon or nitrogen availabilities were significantly influenced by
      clonal integration in the rhizosphere of shaded ramets. Clonal integration
      significantly increased extracellular enzyme activities and abundance of
      functional genes in the rhizosphere of shaded ramets. When rhizomes were
      connected, higher nitrogen turnover (nitrogen mineralization or nitrification
      rates) was exhibited in the rhizosphere of shaded offspring ramets. However,
      nitrogen turnover was significantly decreased by clonal integration in the
      rhizosphere of shaded mother ramets. Path analysis indicated that nitrogen
      turnover in the rhizosphere of shaded, offspring or mother ramets were primarily
      driven by the response of soil microorganisms to dissolved organic carbon or
      nitrogen. This unique in-situ experiment provided insights into the mechanism of
      nutrient recycling mediated by clonal integration. It was suggested that effects
      of clonal integration on the rhizosphere microbial processes were dependent on
      direction of photosynthates transport in clonal plant subjected to heterogeneous
      light conditions.

PMID- 29454201
TI  - Nitrous oxide emissions from near-zero water exchange brackish recirculating
      aquaculture systems.
AB  - The development of intensive recirculating aquaculture systems (RAS) with low
      water exchange has accelerated in recent years as a result of environmental,
      economic and other concerns. In these systems, fish are commonly grown at high
      density, 50 to 150kg/m3, using high-protein (30%-60%) feeds. Typically, the RAS
      consists of a solid treatment and a nitrification unit; in more advanced RAS,
      there is an additional denitrification step. Nitrous oxide (N2O), a byproduct
      during nitrification and denitrification processes, is a potent greenhouse gas
      that destroys the ozone layer. The aim of this study was to measure and assess
      N2O emissions from a near-zero discharge land-based saline RAS. N2O flux was
      monitored from the RAS's fish tank, and moving-bed nitrification and activated
      sludge (with intrinsic C source) denitrification reactors. N2O emission potential
      was also analyzed in the laboratory. N2O flux from the denitrification reactors
      ranged between 6.5 and 48mg/day, equivalent to 1.27+/-1.01% of the removed
      nitrate-N. Direct analysis from the fish tank and nitrification reactors could
      not be performed due to high aeration, which diluted the N2O concentration to
      below detection limits. Thus, its potential emission was estimated in the
      laboratory: from the fishponds, it was negligible; from the nitrification
      reactor, it ranged between 0.4 and 2.8% of the total ammonia-N oxidized. The
      potential N2O emission from the denitrification reactor was 3.72+/-2.75% of the
      reduced nitrate-N, within the range found in the direct measurement. Overall, N2O
      emission during N transformation in a RAS was evaluated to be 885mg/kg feed or
      1.36g/kg fish production, accounting for 1.23% of total N application.
      Consequently, it is estimated that N2O emission from aquaculture currently
      accounts for 2.4% of the total agricultural N2O emission, but will decrease to
      1.7% by 2030.

PMID- 29454202
TI  - Global patterns of extreme drought-induced loss in land primary production:
      Identifying ecological extremes from rain-use efficiency.
AB  - Quantifying the ecological patterns of loss of ecosystem function in extreme
      drought is important to understand the carbon exchange between the land and
      atmosphere. Rain-use efficiency [RUE; gross primary production
      (GPP)/precipitation] acts as a typical indicator of ecosystem function. In this
      study, a novel method based on maximum rain-use efficiency (RUEmax) was developed
      to detect losses of ecosystem function globally. Three global GPP datasets from
      the MODIS remote sensing data (MOD17), ground upscaling FLUXNET observations (MPI
      BGC), and process-based model simulations (BESS), and a global gridded
      precipitation product (CRU) were used to develop annual global RUE datasets for
      2001-2011. Large, well-known extreme drought events were detected, e.g. 2003
      drought in Europe, 2002 and 2011 drought in the U.S., and 2010 drought in Russia.
      Our results show that extreme drought-induced loss of ecosystem function could
      impact 0.9% +/- 0.1% of earth's vegetated land per year and was mainly
      distributed in semi-arid regions. The reduced carbon uptake caused by functional
      loss (0.14 +/- 0.03 PgC/yr) could explain >70% of the interannual variation in
      GPP in drought-affected areas (p <= 0.001). Our results highlight the impact of
      ecosystem function loss in semi-arid regions with increasing precipitation
      variability and dry land expansion expected in the future.

PMID- 29454203
TI  - Metals and arsenic in fish from a Ramsar site under past and present human
      pressures: Consumption risk factors to the local population.
AB  - The risk of metals and As in seafood for traditional populations living in a
      Marine Protected Areas (MPA) is seldom assessed, although the risk of human
      exposure to contaminants is one of the indicators associated with the
      socioeconomic goals of MPAs. The current study aimed to estimate the potential
      risk of some metals (Cd, Pb, and Zn) and arsenic (As) for human health through
      the ingestion of fish locally harvested in a Ramsar site, the Cananeia-Iguape
      Peruibe Environmental Protected Area (APA-CIP). Previous studies showed
      environmental impacts in this area due to former mining activities and
      urbanization. Cathorops spixii, a catfish largely consumed by the local
      population, was collected along the estuary in three seasons with different rain
      regimes. Metals and As loads in muscle tissue were quantified and it was
      estimated (i) the target hazard quotient (THQ) and (ii) the daily intake (EDI)
      for metals and As, (iii) the cancer risk (CRisk) only for As, and (iv) the number
      of eligible meals per month. Cd, Pb, and As were found at concentrations above
      action levels for human consumption. Depending on the level of exposure of the
      local population, the consumption of C. spixii may pose risk to human health.
      Highest THQs were estimated for fish collected in sites closer to the main
      contamination sources in the APA-CIP, i.e. the mouth of Ribeira de Iguape River
      (P1) and the city of Cananeia (P4, P5, and P6). Arsenic showed high levels of
      cancer risk, although restricted to the area close to the city. The exposure of
      the local population to metal and As contaminated seafood cannot be disregarded
      in environmental studies and management of the APA-CIP.

PMID- 29454204
TI  - Scanning vertical distributions of typical aerosols along the Yangtze River using
      elastic lidar.
AB  - In recent years, China has experienced heavy air pollution, especially haze
      caused by particulate matter (PM). The compositions, horizontal distributions,
      transport, and chemical formation mechanisms of PM and its precursors have been
      widely investigated in China based on near-ground measurements. However, the
      understanding of the distributions and physical and chemical processes of PM in
      the vertical direction remains limited. In this study, an elastic lidar was
      employed to investigate the vertical profiles of aerosols along the Yangtze River
      during the Yangtze River Campaign of winter 2015. Some typical aerosols were
      identified and some events were analyzed in three cases. Dust aerosols can be
      transported from the Gobi Desert to the Yangtze River basin across a long
      distance at both low and high altitudes in early December. The transport route
      was perpendicular to the ship track, suggesting that the dust aerosols may have
      affected a large area. Moreover, during transport, some dust was also affected by
      the areas below its transport route since some anthropogenic pollutants were
      mixed with the dust and changed some of its optical properties. Biomass-burning
      aerosols covering a distant range along the Yangtze River were identified. This
      result directly shows the impact areas of biomass-burning aerosols in some
      agricultural fields. Some directly emitted aerosol plumes were observed, and
      direct effects of such plumes were limited both temporally and spatially. In
      addition, an aerosol plume with very low linear depolarization ratios, probably
      formed through secondary processes, was also observed. These results can help us
      better understand aerosols in large spatial scales in China and can be useful to
      regional haze studies.

PMID- 29454205
TI  - How can local representations of changes of the availability in natural resources
      assist in targeting conservation?
AB  - The use and appropriation of natural resources by human groups may be strongly
      related to the perception that these groups have of the abundance or scarcity of
      these resources. Researches on environmental representation can be useful to
      understand the criteria involved in the selection and use of natural resources,
      to verify if people realize changes in the availability of these resources and
      the possible causes of these changes and to elaborate conservation strategies, if
      necessary. However, if people are not realizing these changes, of if they do not
      perceive themselves as a cause of such scarcity, the developing of conservation
      strategies will be very difficult to implement. We investigated the drivers of
      sustainable harvest of Syagrus coronata (Mart.) Becc. (ouricuri palm) leaves by
      the Fulni-o indigenous people in northeastern Brazil and accessed the
      representation of changes in the availability of the populations of this species
      over time. We obtained information about events that, from the point of view of
      the palm harvesters, pose threats to S. coronata populations. More experienced
      local harvesters tend to harvest leaves in a more sustainable manner than did
      young and inexperienced harvesters. The Fulni-o reported a decline in S. coronata
      populations. However, they primarily associate such decline to the farming
      practices of non-indigenous people that lease lands in the area. Although the
      Fulni-o people perceived a shortage of such resource, our findings indicate that
      the implementation of conservation strategies for the ouricuri palm may not be so
      easy to implement, once it affects one of their main income sources (land lease),
      which is recognize as the major threat for the species by harvesters. Ours
      results showed that the relationship between perception of scarcity and ease of
      implementation of conservation actions should be contextualized.

PMID- 29454206
TI  - Less sensitive of urban surface to climate variability than rural in Northern
      China.
AB  - In this study, the relationships between interannual variations of surface urban
      heat islands (SUHIs) and climate variability were studied in 31 cities of China
      for the period 2001-2016. For cold and dry Northern China, it was found that the
      interannual variations of SUHI intensity (SUHII, land surface temperature (LST)
      in urban minus rural) in urban cores was significantly (p<0.05) and negatively
      correlated with rural LST in 9 (in summer days (SDs)) and 8 (in winter days
      (WDs)) of the 15 northern cities, respectively. In addition, the daytime LST
      differences between hot summers and other summers and between cold winters and
      other winters were generally lower in urban cores (1.141 degrees C for SDs and
      2.535 degrees C for WDs) than in rural areas (1.890 degrees C for SDs and 3.377
      degrees C for WDs). The standard deviation was further used to reflect the
      interannual stabilities of LST, enhanced vegetation index (EVI) and white sky
      albedo (WSA). Interestingly, the standard deviations of LST across 2001-2016 were
      generally lower in urban cores (0.994 degrees C for SDs and 1.577 degrees C for
      WDs) than in rural areas (1.431 degrees C for SDs and 2.077 degrees C for WDs).
      Similar results were observed for EVI and WSA (winter). The results suggested
      that the urban surface is less sensitive to climate variability than rural areas
      in Northern China. Comparatively, most findings were less evident in hot and
      humid Southern China. Despite the whole world would become warmer or colder in
      future, the insensitivity of urban surface may mitigate its impacts in cold and
      dry Northern China. However, it does not mean that urbanization is totally good
      due to its environmental problem.

PMID- 29454207
TI  - Repeated treatments of ciprofloxacin and kresoxim-methyl alter their dissipation
      rates, biological function and increase antibiotic resistance in manured soil.
AB  - The dissipation of ciprofloxacin (CIP, 1.0 and 10.0mg/kg) and kresoxim-methyl
      (KM, 1.0 and 2.0mg/kg) in manure-amended soil, the variations in soil enzyme
      activities and microbial functional diversities, and CIP-induced bacterial
      community tolerances were studied using a chromatographic analysis, enzyme
      colorimetric and titration analyses, and the BIOLOG EcoPlate method. Three
      successive treatments of individual and combined samples of CIP and KM at low and
      high concentrations were performed at 60d intervals. The dissipation half-life of
      CIP increased, but that of KM decreased in manured soil with treatment frequency;
      furthermore, the combined treatment altered the dissipation rates of CIP and KM.
      A stronger inhibitory effect on the activities of soil neutral phosphatase and
      urease was observed in the individual KM treatment than in the individual CIP
      treatment. A similar inhibitory trend was also found in soil neutral phosphatase
      activity in the combined treatment at high concentration compared to that at low
      concentration, but the activity of soil catalase was enhanced in the early stages
      of the KM or CIP treatments. Meanwhile, the inhibitory trend on the overall
      activity and functional diversity of soil microorganisms was observed in the
      individual KM or CIP treatment, and the combined treatment exerted a greater
      suppression effect than that in the individual treatment. Bacterial community
      resistance to CIP increased significantly with increasing treatment frequency and
      concentration, and furthermore antibiotic resistance developed faster in the
      combined treatment than in the individual treatment. It was concluded that the
      repeated treatments of CIP and KM could alter their dissipation rates and soil
      enzyme activities, suppress microbial functional diversity, and increase
      bacterial community resistance to CIP in manured soil.

PMID- 29454208
TI  - Barrier effects of remote high mountain on atmospheric metal transport in the
      eastern Tibetan Plateau.
AB  - Anthropogenic metals adsorbed on suspended fine particles can be deposited on
      remote and inaccessible high mountains by long-range atmospheric transport. In
      this study, we investigated the cadmium (Cd) and lead (Pb) in the soils, mosses
      and rainfall of three transects on the Gongga Mountain, eastern Tibetan Plateau,
      to understand the mountain interception effects on their atmospheric transport.
      The concentrations of Cd and Pb in the soils and mosses displayed a pattern of
      eastern transect>northern transect>western transect. The distribution of Cd and
      Pb on the eastern transect increased from 2000 to 2900m a.s.l. (above sea level),
      decreased toward the timberline, and increased again with altitude; on the
      northern transect, it generally decreased with altitude whereas a distribution
      trend was not clearly observed on the western transect. The Cd and Pb
      concentrations in the rainfall of the eastern transect generally decreased with
      altitude, and they were higher inside forests than outside forests and temporally
      higher in the winter than the summer. The Pb isotopic ratios coupled with moss
      bio-monitoring distinguished anthropogenic sources of Cd and Pb on the eastern
      and northern transects, whereas bedrock weathering was the main source of Cd and
      Pb on the western transect. We proposed a conceptual model to delineate the
      effects of terrain, local climate and vegetation on the transport of atmospheric
      metals. Our results highlighted the high mountains in the eastern Tibetan Plateau
      as an effective natural barrier limiting atmospheric metal transport.

PMID- 29454209
TI  - Reconciling discrepancies in the source characterization of VOCs between emission
      inventories and receptor modeling.
AB  - Emission inventory (EI) and receptor model (RM) are two of the three source
      apportionment (SA) methods recommended by Ministry of Environment of China and
      used widely to provide independent views on emission source identifications. How
      to interpret the mixed results they provide, however, were less studied. In this
      study, a cross-validation study was conducted in one of China's fast-developing
      and highly populated city cluster- the Pearl River Delta (PRD) region. By
      utilizing a highly resolved speciated regional EI and a region-wide gridded
      volatile organic compounds (VOCs) speciation measurement campaign, we elucidated
      underlying factors for discrepancies between EI and RM and proposed ways for
      their interpretations with the aim to achieve a scientifically plausible source
      identification. Results showed that numbers of species, temporal and spatial
      resolutions used for comparison, photochemical loss of reactive species,
      potential missing sources in EI and tracers used in RM were important factors
      contributed to the discrepancies. Ensuring the consensus of species used in EIs
      and RMs, utilizing a larger spatial coverage and longer time span, addressing the
      impacts of photochemical losses, and supplementing emissions from missing sources
      could help reconcile the discrepancies in VOC source characterizations acquired
      using both approaches. By leveraging the advantages and circumventing the
      disadvantages in both methods, the EI and RM could play synergistic roles to
      obtain robust SAs to improve air quality management practices.

PMID- 29454210
TI  - Sunshine duration reconstruction in the southeastern Tibetan Plateau based on
      tree-ring width and its relationship to volcanic eruptions.
AB  - Sunshine is as essential as temperature and precipitation for tree growth, but
      sunshine duration reconstructions based on tree rings have not yet been conducted
      in China. In this study, we presented a 497-year sunshine duration reconstruction
      for the southeastern Tibetan Plateau using a width chronology of Abies forrestii
      from the central Hengduan Mountains. The reconstruction accounted for 53.5% of
      the variance in the observed sunshine during the period of 1961-2013 based on a
      stable and reliable linear regression. This reconstructed sunshine duration
      contained six sunny periods (1630-1656, 1665-1697, 1731-1781, 1793-1836, 1862
      1895 and 1910-1992) and seven cloudy periods (1522-1629, 1657-1664, 1698-1730,
      1782-1792, 1837-1861, 1896-1909 and 1993-2008) at a low-frequency scale. There
      was an increasing trend from the 16th century to the late 18th and early 19th
      centuries and a decreasing trend from the mid-19th to the early 21st centuries.
      Sunshine displayed inverse patterns to the local Palmer drought severity index on
      a multidecadal scale, indicating that this region likely experienced droughts
      under more sunshine conditions. The decrease in sunshine particularly in recent
      decades was mainly due to increasing atmospheric anthropogenic aerosols. In terms
      of the interannual variations in sunshine, weak sunshine years matched well with
      years of major volcanic eruptions. The significant cycles of the 2- to 7-year,
      20.0-year and 35.2-year durations as well as the 60.2-year and 78.7-year
      durations related to the El-Nino Southern Oscillation, the Pacific Decadal
      Oscillation and the Atlantic Multidecadal Oscillation suggested that the
      variation in sunshine duration in the southeastern Tibetan Plateau was possibly
      affected by large-scale ocean-atmosphere circulations.

PMID- 29454211
TI  - Seasonality, water use and community management of water systems in rural
      settings: Qualitative evidence from Ghana, Kenya, and Zambia.
AB  - The sustainability of rural, community-managed water systems in sub-Saharan
      Africa depends in part on the ability of local water committees to repair
      breakdowns and carry out the operation and maintenance (O&M) of the system. Much
      of sub-Saharan Africa has two distinct seasons that affect the availability of
      water sources and how people use water. Little is known about how seasonality
      affects water system management. This qualitative study is based on 320
      interviews and focus group discussions and examines the effects of season on
      community water use and management in Ghana, Kenya and Zambia. Participants
      revealed that seasonality affects water availability, water system breakdowns,
      resource mobilization, committee activity, and external support availability. In
      the rainy season, participants typically reported spending less time and money on
      water collection because rainwater harvesting and seasonal streams, ponds, wells
      and reservoirs are available. In the dry season, people used improved groundwater
      sources more often and spent more money and time collecting water. Although
      seasonal changes in household water demand and use have been examined previously,
      our data suggest that seasonality also influences community management through
      differential water system use, system breakdowns and management characteristics.
      We found that water committees generally have less money, time and access to
      external support during the rainy season, making them less able to carry out O&M.
      Our results suggest that community engagement should take place over a long
      period of time so that seasonal patterns in management can be understood and
      incorporated into water committee training. External support actors should make a
      more targeted effort to understand the cultural and economic patterns in a
      community in order to train committees with appropriate management strategies.

PMID- 29454212
TI  - Adsorption of sulfamethoxazole by magnetic biochar: Effects of pH, ionic
      strength, natural organic matter and 17alpha-ethinylestradiol.
AB  - Recent studies have shown the widespread occurrence of pharmaceuticals in the
      aquatic environment leading to increasing global concern on their potential
      adverse effects in the environment and public health. In this study, we evaluated
      the use of magnetic biochar derived from pine sawdust, one of New Zealand's major
      wood wastes, to remove an emerging contaminant, sulfamethoxazole (SMX), at
      different pH, ionic strength, natural organic matter (NOM) and a competing
      compound, 17alpha-ethinylestradiol (EE2). In single-solute system, the sorption
      of SMX onto magnetic biochar was found to be highly pH-dependent and slightly
      increased with increase in ionic strength. However, the effects of pH, ionic
      strength and NOM were relatively insignificant compared to the sorption
      inhibition caused by EE2 in binary-solute system. Both SMX and EE2 sorption onto
      the highly carbonised biochar in magnetic biochar were postulated to be due to
      the pi-pi electron donor acceptor and hydrophobic interaction. EE2 is more
      hydrophobic than SMX. Hence, strong competition between these compounds was
      identified where EE2 markedly inhibited the sorption of SMX onto magnetic biochar
      in all artificial environmental conditions studied.

PMID- 29454213
TI  - Spatio-temporal comparison of neustonic microplastic density in Hong Kong waters
      under the influence of the Pearl River Estuary.
AB  - Rivers are recognised as an important source of plastic debris in the open sea.
      The Pearl River in China is estimated to transport 0.1milliontonnes of plastic
      waste to the open sea annually. However, no empirical study has been conducted to
      assess the plastic contamination levels in the Pearl River Estuary. Hong Kong is
      situated in the east of the Pearl River Estuary; its western waters are strongly
      influenced by river discharge, whereas the eastern waters are unaffected by the
      freshwater plume. In this study, we quantified the neustonic plastic debris
      density in the western and eastern waters of Hong Kong. The mean microplastic
      (0.355-4.749mm) and large plastic debris (>=4.75mm) densities in the western side
      were 3.627 and 0.758n/m3, respectively. Seasonal comparisons indicated that both
      size classes of plastic debris were significantly more abundant by number in the
      rainy season than the dry season (p<0.001). However, the influence of rivers on
      plastic density at the sea surface may be highly restricted to the estuarine
      delta, as no significant spatial difference was found between the western and
      eastern waters.

PMID- 29454214
TI  - Observation of the degradation of three types of plastic pellets exposed to UV
      irradiation in three different environments.
AB  - Plastic debris represents one of the most prevalent and persistent pollution
      problems in the marine environment. In particular, microplastics that are mainly
      degraded from larger plastic debris have become a growing environmental concern.
      However, studies on the degradation of plastics in the aquatic environment that
      hydrobios reside in have been limited, while several studies regarding the
      degradation of plastics have been conducted under outdoor or accelerated
      weathering conditions. Thus, observation of the degradation of three types of
      virgin plastic pellets exposed to UV irradiation in three different environments
      (i.e., simulated seawater, ultrapure water, and a waterless (air) condition) was
      carried out. Data on the changes in physical and chemical properties were
      collected. The FTIR spectra showed that hydroxyl groups and carbonyl groups
      developed in three types of weathered plastic pellets under the air and ultrapure
      water environmental conditions after 3months of UV irradiation, while only
      carbonyl groups were found in plastic pellets in the simulated seawater
      environment. In contrast, the Raman spectra showed no significant changes in the
      weathered plastic pellets, but there were different intensities of characteristic
      peaks after exposure to UV irradiation. In addition, SEM images illustrated that
      granular oxidation, cracks and flakes were common patterns during degradation,
      and the plastic pellets in the three different environments experienced different
      levels of chemical weathering. We suggest that further studies on the degradation
      processes of plastic debris are needed to predict the fate of plastic debris in
      the environment.

PMID- 29454215
TI  - Effect-based trigger values for in vitro and in vivo bioassays performed on
      surface water extracts supporting the environmental quality standards (EQS) of
      the European Water Framework Directive.
AB  - Effect-based methods including cell-based bioassays, reporter gene assays and
      whole-organism assays have been applied for decades in water quality monitoring
      and testing of enriched solid-phase extracts. There is no common EU-wide
      agreement on what level of bioassay response in water extracts is acceptable. At
      present, bioassay results are only benchmarked against each other but not against
      a consented measure of chemical water quality. The EU environmental quality
      standards (EQS) differentiate between acceptable and unacceptable surface water
      concentrations for individual chemicals but cannot capture the thousands of
      chemicals in water and their biological action as mixtures. We developed a method
      that reads across from existing EQS and includes additional mixture
      considerations with the goal that the derived effect-based trigger values (EBT)
      indicate acceptable risk for complex mixtures as they occur in surface water.
      Advantages and limitations of various approaches to read across from EQS are
      discussed and distilled to an algorithm that translates EQS into their
      corresponding bioanalytical equivalent concentrations (BEQ). The proposed EBT
      derivation method was applied to 48 in vitro bioassays with 32 of them having
      sufficient information to yield preliminary EBTs. To assess the practicability
      and robustness of the proposed approach, we compared the tentative EBTs with
      observed environmental effects. The proposed method only gives guidance on how to
      derive EBTs but does not propose final EBTs for implementation. The EBTs for some
      bioassays such as those for estrogenicity are already mature and could be
      implemented into regulation in the near future, while for others it will still
      take a few iterations until we can be confident of the power of the proposed EBTs
      to differentiate good from poor water quality with respect to chemical
      contamination.

PMID- 29454216
TI  - Non-linear effects of mean temperature and relative humidity on dengue incidence
      in Guangzhou, China.
AB  - BACKGROUND: Dengue fever is an important infectious disease in Guangzhou, China;
      previous studies on the effects of weather factors on the incidence of dengue
      fever did not consider the linearity of the associations. METHODS: This study
      evaluated the effects of daily mean temperature, relative humidity and rainfall
      on the incidence of dengue fever. A generalized additive model with splines
      smoothing function was performed to examine the effects of daily mean, minimum
      and maximum temperatures, relative humidity and rainfall on incidence of dengue
      fever during 2006-2014. RESULTS: Our analysis detected a non-linear effect of
      mean, minimum and maximum temperatures and relative humidity on dengue fever with
      the thresholds at 28 degrees C, 23 degrees C and 32 degrees C for daily mean,
      minimum and maximum temperatures, 76% for relative humidity, respectively. Below
      the thresholds, there was a significant positive effect, the excess risk in
      dengue fever for each 1 degrees C in the mean temperature at lag7-14days was
      10.21%, (95% CI: 6.62% to 13.92%), 7.10% (95% CI: 4.99%, 9.26%) for 1 degrees C
      increase in daily minimum temperature in lag 11days, and 2.27% (95% CI: 0.84%,
      3.72%) for 1 degrees C increase in daily maximum temperature in lag 10days; and
      each 1% increase in relative humidity of lag7-14days was associated with 1.95%
      (95% CI: 1.21% to 2.69%) in risk of dengue fever. CONCLUSIONS: Future prevention
      and control measures and epidemiology studies on dengue fever should consider
      these weather factors based on their exposure-response relationship.

PMID- 29454217
TI  - Morphologies and elemental compositions of local biomass burning particles at
      urban and glacier sites in southeastern Tibetan Plateau: Results from an
      expedition in 2010.
AB  - Many studies indicate that the atmospheric environment over the southern part of
      the Tibetan Plateau is influenced by aged biomass burning particles that are
      transported over long distances from South Asia. However, our knowledge of the
      particles emitted locally (within the plateau region) is poor. We collected
      aerosol particles at four urban sites and one remote glacier site during a
      scientific expedition to the southeastern Tibetan Plateau in spring 2010. Weather
      and backward trajectory analyses indicated that the particles we collected were
      more likely dominated by particles emitted within the plateau. The particles were
      examined using an electron microscope and identified according to their sizes,
      shapes and elemental compositions. At three urban sites where the anthropogenic
      particles were produced mainly by the burning of firewood, soot aggregates were
      in the majority and made up >40% of the particles by number. At Lhasa, the
      largest city on the Tibetan Plateau, tar balls and mineral particles were also
      frequently observed because of the use of coal and natural gas, in addition to
      biofuel. In contrast, at the glacier site, large numbers of chain-like soot
      aggregates (~25% by number) were noted. The morphologies of these aggregates were
      similar to those of freshly emitted ones at the urban sites; moreover, physically
      or chemically processed ageing was rarely confirmed. These limited observations
      suggest that the biomass burning particles age slowly in the cold, dry plateau
      air. Anthropogenic particles emitted locally within the elevated plateau region
      may thus affect the environment within glaciated areas in Tibet differently than
      anthropogenic particles transported from South Asia.

PMID- 29454218
TI  - Atmospheric pattern of volatile organochlorine compounds and hexachlorobenzene in
      the surroundings of a chlor-alkali plant.
AB  - The outdoor atmospheric distributions of chlorinated volatile organic compounds
      (VOCs) from locations receiving the emissions of a chlor-alkali plant have been
      studied. Trichloroethylene and tetrachloroethylene (medians 2.4 MUg/m3 and 1.7
      MUg/m3, respectively) were the most abundant compounds, which was in accordance
      with the production processes from these installations. The concentrations of
      trichlorofluoromethane, median 1.6 MUg/m3, are rather similar to the average
      levels described in general in the troposphere and cannot be attributed to this
      specific source. Several by-products involving dichloroacetylene, carbon
      tetrachloride, hexachloroethane, hexachlorobutadiene, trans-1H-pentachloro-1,3
      butadiene, 2H-pentachloro-1,3-butadiene, cis-1H-pentachloro-1,3-butadiene,
      tetrachloro- and trichloro-butadienes and hexachlorobenzene were also identified.
      Some of these compounds, e.g. carbon tetrachloride, chloroform and
      tetrachloroethane, could also have been manufactured during some periods. The
      occurrence of these manufactured compounds and by-products in the atmosphere
      could also reflect, at least in part, volatilization during the extraction of
      previously discharged chlor-alkali residues developed within the environmental
      restoration program of the Flix water reservoir. In this respect, the tri-, tetra
      and pentachloro-1,3-butadienes could also originate from microbial
      transformation in the solid deposits accumulated in the water reservoir which
      were volatilized after extraction. Among all identified VOCs, trichloroethylene
      showed the highest health risks considering the measured airborne concentrations
      and the WHO and USEPA recommendations.

PMID- 29454219
TI  - Reading skill related to left ventral occipitotemporal cortex during a
      phonological awareness task in 5-6-year old children.
AB  - The left ventral occipitotemporal cortex (vOT) is important in visual word
      recognition. Studies have shown that the left vOT is generally observed to be
      involved in spoken language processing in skilled readers, suggesting automatic
      access to corresponding orthographic information. However, little is known about
      where and how the left vOT is involved in the spoken language processing of young
      children with emerging reading ability. In order to answer this question, we
      examined the relation of reading ability in 5-6-year-old kindergarteners to the
      activation of vOT during an auditory phonological awareness task. Two
      experimental conditions: onset word pairs that shared the first phoneme and rhyme
      word pairs that shared the final biphone/triphone, were compared to allow a
      measurement of vOT's activation to small (i.e., onsets) and large grain sizes
      (i.e., rhymes). We found that higher reading ability was associated with better
      accuracy of the onset, but not the rhyme, condition. In addition, higher reading
      ability was only associated with greater sensitivity in the posterior left vOT
      for the contrast of the onset versus rhyme condition. These results suggest that
      acquisition of reading results in greater specialization of the posterior vOT to
      smaller rather than larger grain sizes in young children.

PMID- 29454220
TI  - Early life sexual abuse is associated with increased suicide attempts: An update
      meta-analysis.
AB  - Suicide is an emerging, yet preventable global health issue associated with
      significant mortality. Identification of underlying risk factors and antecedents
      may inform preventive strategies and interventions. This study serves to provide
      an updated meta-analysis examining the extent of association of early life sexual
      abuse with suicide attempts. Using the keywords [early abuse OR childhood abuse
      OR sexual OR rape OR molest* OR violence OR trauma OR PTSD] AND [suicid* OR
      premature OR unnatural OR deceased OR died OR mortality], a preliminary search on
      the PubMed, Ovid, PsychINFO, Web of Science and Google Scholar databases yielded
      12,874 papers published in English between 1-Jan-1988 and 1-June-2017. Of these,
      only 47 studies were included in the final meta-analysis. The 47 studies (25
      cross-sectional, 14 cohort, 6 case-control and 2 twin studies) contained a total
      of 151,476 subjects. Random-effects meta-analysis found early life sexual abuse
      to be a significant risk factor for suicide attempts, compared to baseline
      population (pooled OR 1.89, 95% CI: 1.66 to 2.12, p < 0.001). Subgroup analyses
      of cross-sectional and longitudinal studies showed similar findings of increased
      risk as they yielded ORs of 1.98 (95% CI: 1.70 to 2.25, p < 0.001) and 1.65 (95%
      CI: 1.37 to 1.93, p < 0.001), respectively. In both cross-sectional and
      longitudinal studies, childhood sexual abuse was consistently associated with
      increased risk of suicide attempts. The findings of the present study provide
      strong grounds for funding public policy planning and interventions to prevent
      sexual abuse and support its victims. Areas for future research should include
      preventive and treatment strategies and factors promoting resilience following
      childhood sexual abuse. Future research on the subject should have more robust
      controls and explore the differential effects of gender and intra-versus extra
      familial sexual abuse.

PMID- 29454222
TI  - Obesity, dyslipidemia and brain age in first-episode psychosis.
AB  - INTRODUCTION: Obesity and dyslipidemia may negatively affect brain health and are
      frequent medical comorbidities of schizophrenia and related disorders. Despite
      the high burden of metabolic disorders, little is known about their effects on
      brain structure in psychosis. We investigated, whether obesity or dyslipidemia
      contributed to brain alterations in first-episode psychosis (FEP). METHODS: 120
      participants with FEP, who were undergoing their first psychiatric
      hospitalization, had <24 months of untreated psychosis and were 18-35 years old
      and 114 controls within the same age range participated in the study. We acquired
      3T brain structural MRI, fasting lipids and body mass index. We used machine
      learning trained on an independent sample of 504 controls to estimate the
      individual brain age of study participants and calculated the BrainAGE score by
      subtracting the chronological from the estimated brain age. RESULTS: In a
      multiple regression model, the diagnosis of FEP (B = 1.15, SE B = 0.31, p <
      0.001) and obesity/overweight (B = 0.92, SE B = 0.35, p = 0.008) were each
      additively associated with BrainAGE scores (R2 = 0.22, F(3, 230) = 21.92, p <
      0.001). BrainAGE scores were highest in participants with FEP and
      obesity/overweight (3.83 years, 95%CI = 2.35-5.31) and lowest in normal weight
      controls (-0.27 years, 95%CI = -1.22-0.69). LDL-cholesterol, HDL-cholesterol or
      triglycerides were not associated with BrainAGE scores. CONCLUSIONS:
      Overweight/obesity may be an independent risk factor for diffuse brain
      alterations manifesting as advanced brain age already early in the course of
      psychosis. These findings raise the possibility that targeting metabolic health
      and intervening already at the level of overweight/obesity could slow brain
      ageing in FEP.

PMID- 29454221
TI  - 13C-phenylalanine breath test and serum biopterin in schizophrenia, bipolar
      disorder and major depressive disorder.
AB  - Phenylalanine is required for the synthesis of the neurotransmitters dopamine,
      noradrenaline, and adrenaline. The rate-limiting step for phenylalanine
      metabolism is catalyzed by phenylalanine hydroxylase (PAH) and its cofactor
      tetrahydrobiopterin. We aimed to detect altered phenylalanine metabolism in major
      psychiatric disorders using the l-[1-13C]phenylalanine breath test (13C-PBT) and
      serum biopterin levels. We also investigated association of PAH mutations with
      schizophrenia and phenylalanine metabolism. 13C-phenylalanine (100 mg) was orally
      administered, and the breath 13CO2/12CO2 ratio was monitored for 120 min in four
      groups: 103 patients with schizophrenia (DSM-IV), 39 with bipolar disorder, 116
      with major depressive disorder (MDD), and 241 healthy controls. Serum biopterin
      levels were measured by high performance liquid chromatography. Mutation
      screening of PAH exons was performed by direct sequencing in 46 schizophrenia
      patients. Association analysis was performed using six tag single nucleotide
      polymorphisms and the PAH Arg53His mutation by TaqMan assays in 616 schizophrenia
      patients and 1194 healthy controls. Analyses of covariance controlling for age,
      sex, and body weight showed that the index for the amount of exhaled 13CO2 was
      significantly lower in the schizophrenia group than in the other three groups
      (all p < 0.05). Biopterin levels in schizophrenia and MDD were significantly
      lower than those in controls. Biopterin levels correlated with 13C-PBT indices in
      controls. PAH polymorphisms were not associated with schizophrenia or 13C-PBT
      indices. 13C-PBT revealed reduced phenylalanine metabolism in schizophrenia,
      though we obtained no evidence of involvement of PAH polymorphism. Serum
      biopterin levels were lower in schizophrenia and MDD, warranting further
      investigation.

PMID- 29454223
TI  - Attention as the 'glue' for object integration in parietal extinction.
AB  - Patients with unilateral, parietal brain damage frequently show visual
      extinction, which manifests in a failure to identify contralesional stimuli when
      presented simultaneously with other, ipsilesional stimuli (but full awareness for
      single stimulus presentations). Extinction reflects an impairment of spatial
      selective attention, leaving basic preattentive processing unaffected. For
      instance, access to bilaterally grouped objects is usually spared in extinction,
      suggesting that grouping occurs at a stage preceding (in the patients: abnormally
      biased) spatial-attentional selection. Here, we reinvestigated this notion by
      comparing (largely between participants, but also within a single-case
      participant) conditions with objects that varied in their dominant direction of
      grouping: from the attended to the non-attended hemifield (data from Conci et
      al., 2009) versus from the non-attended to the attended hemifield (new data). We
      observe complete absence of extinction when shape completion extended from the
      attended hemifield. By contrast, extinction was not diminished when object
      groupings propagate from the unattended hemifield. Moreover, we found the
      individual severity of the attentional impairment (assessed by a standard
      "inattention" test) to be directly related to the degree of completion in the
      unattended hemifield. This pattern indicates that grouping can overcome visual
      extinction only when object integration departs from the attended visual field,
      implying, contrary to many previous accounts, that attention is crucial for
      grouping to be initiated.

PMID- 29454224
TI  - The consonant/vowel pattern determines the structure of orthographic
      representations in the left fusiform gyrus.
AB  - Recent findings demonstrated readers' sensitivity to the distinction between
      consonant and vowel letters. Especially, the way consonants and vowels are
      organised within written words determines their perceptual structure. The present
      work attempted to overcome two limitations of previous studies by examining the
      neurophysiological correlates of this perceptual structure through
      magnetoencephalography (MEG). One aim was to establish that the extraction of
      vowel-centred units takes place during early stages of processing. The second
      objective was to confirm that the vowel-centred structure pertains to the word
      recognition system and may constitute one level in a hierarchy of neural
      detectors coding orthographic strings. Participants performed a cross-case
      matching task in which they had to judge pairs of stimuli as identical or
      different. The critical manipulation concerned pairs obtained by transposing two
      letters, so that the vowel-centred structure was either preserved (FOUVERT
      fovuert, two vowel letter clusters) or modified (BOUVRET-bovuret). Mismatches
      were detected faster when the structure was modified. This effect was associated
      with a significant difference in evoked neuromagnetic fields extending from 129
      to 239 msec after the stimulation. Source localization indicated a significant
      effect in the visual word form area around 200 msec. The results confirm the
      hypothesis that the vowel-centred structure is extracted during the early phases
      of letter string processing and that it is encoded in left fusiform regions
      devoted to visual word recognition.

PMID- 29454225
TI  - Low power lasers on genomic stability.
AB  - Exposure of cells to genotoxic agents causes modifications in DNA, resulting to
      alterations in the genome. To reduce genomic instability, cells have DNA damage
      responses in which DNA repair proteins remove these lesions. Excessive free
      radicals cause DNA damages, repaired by base excision repair and nucleotide
      excision repair pathways. When non-oxidative lesions occur, genomic stability is
      maintained through checkpoints in which the cell cycle stops and DNA repair
      occurs. Telomere shortening is related to the development of various diseases,
      such as cancer. Low power lasers are used for treatment of a number of diseases,
      but they are also suggested to cause DNA damages at sub-lethal levels and alter
      transcript levels from DNA repair genes. This review focuses on genomic and
      telomere stabilization modulation as possible targets to improve therapeutic
      protocols based on low power lasers. Several studies have been carried out to
      evaluate the laser-induced effects on genome and telomere stabilization
      suggesting that exposure to these lasers modulates DNA repair mechanisms,
      telomere maintenance and genomic stabilization. Although the mechanisms are not
      well understood yet, low power lasers could be effective against DNA harmful
      agents by induction of DNA repair mechanisms and modulation of telomere
      maintenance and genomic stability.

PMID- 29454226
TI  - Dysphagia and laryngeal pathology in post-surgical cardiothoracic patients.
AB  - PURPOSE: Cardiothoracic surgery is known to result in dysphagia and laryngeal
      injury. While prevalence has been explored, extent, trajectory and longevity of
      symptoms are poorly understood. This retrospective, observational study explored
      dysphagia and laryngeal injury in patients following cardiothoracic surgery
      referred for instrumental swallowing assessment. METHODS: Clinical notes and
      endoscopic recordings of 106 patients (age range 18-87yrs; mean 63yrs; SD 15yrs)
      (including 190 endoscopes) at one large tertiary centre were reviewed by two
      speech-language pathologists and a laryngologist. Standardized measures of
      laryngeal anatomy and physiology, New Zealand Secretion Scale, Penetration
      Aspiration scale and Yale Residue Scale were rated. RESULTS: Prevalence of
      abnormality included 39% silent aspiration, 65% laryngeal edema and 61% vocal
      paralysis. The incidence of pneumonia was 36% with a post-operative stroke rate
      of 14%. Forty percent of patients were receiving a standard diet by discharge
      from acute care; while, 24% continued to require enteral feeding and 8% received
      laryngeal surgery within twelve months of discharge. Vocal fold motion impairment
      was significantly associated with ventilation time and tracheostomy tube duration
      (p<.05). CONCLUSION: Early endoscopic assessment for identification of dysphagia
      and laryngeal injury in patients following cardiothoracic surgery may allow early
      management and prevention of secondary complications.

PMID- 29454227
TI  - A pilot trial of l-carnitine in patients with traumatic brain injury: Effects on
      biomarkers of injury.
AB  - OBJECTIVE: To investigate the effects of l-Carnitine on neuron specific enolase
      (NSE) as a marker of inflammation in patients with traumatic brain injury (TBI).
      METHODS: Forty patients with severe TBI were randomized into 2 groups. The (LCA-)
      group received standard treatment with placebo while the (LCA+) group received l
      Carnitine 2g/day for one week. NSE was measured on days 1, 3 and 7 after the
      initiation of the study. Neurocognitive and neurobehavioral disorders were
      recorded on the first and third months. RESULTS: Neurocognitive function and NSE
      significantly improved within one week in both groups. Patient mortality was
      similar in LCA+ and LCA- groups (P value: 0.76). Brain edema was present in 7
      patients in LCA+ group and 13 patients in LCA-group (P value: 0.044). While there
      was no difference in NSE levels between the two groups. Neurological function was
      preserved in the LCA+ group with an exception of attention deficit, which was
      frequent in the LCA+ group. CONCLUSION: We concluded that despite improvements in
      neurobehavioral function and the degree of cerebral edema, 7-days of treatment
      with l-Carnitine failed to reduce serum NSE levels or improve mortality rate at
      90days in patients with TBI.

PMID- 29454228
TI  - Obturator internus muscle abscess caused by methicillin-resistant Staphylococcus
      aureus in an adult: A case report.
AB  - INTRODUCTION: Obturator internus muscle (OIM) abscess is a rare condition,
      usually affecting children after trauma or muscular effort. Blood cultures always
      yield positive findings, with Staphylococcus aureus being the most common
      culprit. There are few reports in adults. PRESENTATION OF CASE: We report a case
      of OIM abscess in an adult. A 24-year-old male was admitted to our hospital
      because of right hip pain and fever. He was diagnosed with OIM abscess, and
      methicillin-resistant Staphylococcus aureus (MRSA) was detected on bacterial
      examination. The patient was successfully treated with a surgical drainage
      procedure and antibiotics. DISCUSSION: There are only five reported cases of OIM
      abscess in adults. The patient had no history of recent hip trauma, but had
      intractable acronyx of the right great toe, which was being treated for 2 years.
      MRSA was also detected from cultures of samples obtained from the toe. A toe
      infection can lead to bacteremia. CONCLUSION: In conclusion, we report the first
      case of OIM abscess in an adult caused by MRSA. Surgical drainage, debridement,
      and systemic antibiotic treatment were administered, resulting in a successful
      outcome.

PMID- 29454229
TI  - Pancreatic cancer presenting as colonic disease. A rare case report.
AB  - INTRODUCTION: Pancreatic cancer is the fourth major cause of cancer-related
      deaths. About 50% of the patients are diagnosed with advanced disease. Metastatic
      disease to the colon is a very rare entity with only 5 cases described in english
      literature. CASE PRESENTATION: Male, 60 years-old, presents to a surgical consult
      with the diagnosis of an adenocarcinoma of the sigmoid colon. The physical exam
      revealed a periumbilical nodule with suspicious features. The staging CT-scan
      showed a mass in the tail of the pancreas involving the spleen and left kidney,
      thickening of the sigmoid colon, multiple mesenteric masses and trabecular
      changes in the ischium, suggesting metastatic disease. The case was discussed by
      a multidisciplinary team and it was decided to do a biopsy of the umbilical
      nodule and review the specimen obtained in colonoscopy. Pathological analysis
      revealed a metastasis from pancreatic adenocarcinoma. The patient was proposed to
      start palliative chemotherapy for metastatic pancreatic cancer. After 2 cycles of
      FOLFOX the patient was admitted in the OR with a perforation of the sigmoid mass.
      He was submitted to a sigmoidectomy with end colostomy, with discharge at the 5th
      postoperative day. Pathological analysis of the specimen confirmed the pancreatic
      origin of the tumor. Patient proceeded with palliative treatment, with death 9
      months after the diagnosis. DISCUSSION: Pancreatic metastasis to the colon is a
      very rare entity. Care should be taken when addressing these patients.
      CONCLUSION: Although rare, a sigmoid tumor in a patient with known pancreatic
      adenocarcinoma must raise the suspicion of metastasis.

PMID- 29454230
TI  - The effects of pressure biofeedback training on infraspinatus muscle activity and
      muscle thickness.
AB  - The aim of this study was to investigate muscle activity in the infraspinatus and
      posterior deltoid and infraspinatus muscle thickness during a prone external
      rotation (PER) exercise using pressure biofeedback. Fifteen healthy men
      participated in this study, performing PER exercise with pressure biofeedback
      under four conditions (comfortable, 2 mm Hg, 4 mm Hg, and 8 mm Hg). Surface
      electromyography (EMG) was used to monitor infraspinatus and posterior deltoid
      muscle activity, and ultrasonography was used to collect infraspinatus muscle
      thickness data. Infraspinatus activity and muscle thickness were greatest at 2 mm
      Hg pressure feedback, and both measures were significantly different from those
      under other pressure feedback conditions (p < 0.05). In contrast, posterior
      deltoid activity was lower at 2 mm Hg. However, there was no significant
      difference between any of the four pressure feedback conditions. These findings
      suggest that PER exercise with pressure biofeedback, particularly at 2 mm Hg, is
      effective in selectively activating the infraspinatus muscle.

PMID- 29454231
TI  - Influence of heading perception in the control of posture.
AB  - The optic flow visual input directly influences the postural control. The aim of
      the present study was to examine the relationship between visually induced
      heading perception and postural stability, using optic flow stimulation. The dots
      were accelerated to simulate a heading direction to the left or to the right of
      the vertical midline. The participants were instructed to indicate the perceived
      optic flow direction by making a saccade to the simulated heading direction. We
      simultaneously acquired electromyographyc and center of pressure (COP) signals.
      We analysed the postural sway during three different epochs: (i) the first 500 ms
      after the stimulus onset, (ii) 500 ms before saccade onset, epoch in which the
      perception is achieved and, (iii) 500 ms after saccade onset. Participants
      exhibited a greater postural instability before the saccade, when the perception
      of heading was achieved, and the sway increased further after the saccade. These
      results indicate that the conscious representation of the self-motion affects the
      neural control of posture more than the mere visual motion, producing more
      instability when visual signals are contrasting with eye movements. It could be
      that part of these effects are due to the interactions between gaze shift and
      optic flow.

PMID- 29454232
TI  - Effects of mine tailing and mixed contamination on metals, trace elements
      accumulation and histopathology of the chub (Squalius cephalus) tissues: Evidence
      from three differently contaminated sites in Serbia.
AB  - Chub (Squalius cephalus) specimens were collected in Korenita River seven months
      after spillover from the waste water of antimony mine tailing pond and compared
      with chub living in Kruscica reservoir (intended for water supply) and Meduvrsje
      reservoir (influenced by intense emission of industrial, urban and rural
      wastewater). Concentrations of 15 elements (Al, As, B, Ba, Cd, Cr, Cu, Fe, Hg,
      Mn, Ni, Pb, Si, Sr, Zn) were determined in muscle, liver and gills of chub by
      inductively coupled plasma optical spectrometry (ICP-OES) and histopathological
      alterations in liver and gills were assessed. Chub specimens from Korenita River
      had higher concentrations of As, Ba and Pb in all three investigated tissues as
      well as higher total histopathological index values than chub from reservoirs.
      Specimens from Meduvrsje reservoir were characterized by higher values for
      concentrations of Cu and Si in muscle tissue and higher values for regressive
      histopathological alterations in gills. Individuals of chub from Kruscica
      reservoir had the highest concentrations of Fe in liver, Hg in muscle and Sr and
      Zn in muscle while gills had the lowest value of total histopathological index.
      The results from the present study showed higher level of histopathological
      alterations as a result of mine tailing accident. As a result of mixed
      contamination on the Meduvrsje site, histopathological index values of gills were
      in line with the index value from Korenita River. Increased values for Fe and Sr
      in chub tissue from Kruscica reservoir could be explained by geological structure
      of the site which is characterized by magmatic rock rich in Cu, Fe and Ni as well
      as dominant carbonate sediment complex of marine origin with increased level of
      Sr.

PMID- 29454233
TI  - Combined effect of water inundation and heavy metals on the photosynthesis and
      physiology of Spartina alterniflora.
AB  - The frequency and duration of tidal flooding significantly influence the
      bioavailability of heavy metals (HMs) in sediment and hence exert toxicological
      effects on coastal wetland plants. In this study, the combined effects of
      different water inundation times (3, 6, 9, and 12 h) and HMs (Cu, Zn, Pb, and Cr)
      on the photosynthesis and physiology of Spartina alterniflora were investigated
      under greenhouse conditions. Results showed that S. alterniflora was somehow
      tolerant to the combined HMs treatments, and only the highest level of HM
      treatment decreased leaf chlorophyll content. Furthermore, the plants did not
      show any signs of victimization. Different times of water inundation with HMs did
      not exert any significant effect on the malonaldehyde (MDA) and chlorophyll
      contents in the leaves of S. alterniflora at day 20. Prolonged water inundation
      time at day 60 significantly reduced leaf chlorophyll content with the decrease
      in leaf photosynthetic rate, which was accompanied by a significant increase in
      the intercellular concentration of CO2. At day 60, abscisic acid dose-dependently
      increased along the different water inundation times, indicating that this
      phytohormone is involved in plant responses to flooding stress. Peroxidase (POD),
      superoxide dismutase (SOD), and ascorbate peroxidase (APX), showed different
      responses to the combined treatment of water inundation and HMs at different
      times. At day 20, the long duration of water inundation and HMs treatments (9
      h+HMs and/or 12 h+HMs) significantly increased enzyme activity in the leaves
      compared with the control group (6 h). At day 60, the POD and SOD activities in
      the leaves of S. alterniflora decreased with prolonged water inundation time, and
      root APX activity significantly decreased compared with the 6 h water inundation
      treatment.

PMID- 29454234
TI  - Diarylheptanoid from rhizomes of Curcuma kwangsiensis (DCK) inhibited imiquimod
      induced dendritic cells activation and Th1/Th17 differentiation.
AB  - BACKGROUND AND OBJECT: Dendritic cells (DCs) are critical for initiating the
      activation and differentiation of T cells in inflammatory diseases including
      psoriasis. Curcuma kwangsiensis S.G. Lee & C.F. Liang is a herb for treating
      psoriasis and we previously found Diarylheptanoid from rhizomes of Curcuma
      kwangsiensis (DCK) inhibited keratinocytes proliferation. However, it is unknown
      whether DCK influences DC functions. Thus we aimed to explore whether DCK affect
      the major immunological functions of DCs. MATERIALS AND METHODS: Primary DCs
      derived from mouse bone marrow cells and spleen were used for examining their
      general immunological functions, and OVA-specific T cells from OT-II mice were
      used for examining the DC-mediated T-helper (Th) 1 and Th17 cells differentiation
      and effect. RESULTS: We demonstrated DCK suppressed DC uptake of FITC-labeled
      ovalbumin (OVA) and DC maturation characterized by decreased MHCII, CD80 and CD86
      following imiquimod (IMQ) stimulation. DCK also reduced DC expression of the
      lymphoid-homing chemokine receptor CCR7, and DC migration towards CCL21, the
      ligand for CCR7. Importantly, DCK significantly reduced the production of
      proinflammatory cytokines including IL-12, IL-6 and IL-1beta by IMQ-stimulated
      DCs. Moreover, in the coculture of OVA323-339 peptide-pulsed DCs and OVA-specific
      T cells from OT-II mice, DCK significantly inhibited T cell proliferation and the
      differentiation of Th1 and Th17 cells. Furthermore, DCK treatment greatly reduced
      phosphorylation of p65-associated cell signaling pathway in IMQ-stimulated DCs.
      CONCLUSION: These data together demonstrate a potential role of DCK in
      suppressing the biological function of DCs, and provide a possible mechanism for
      understanding the effects of herb Curcuma kwangsiensis in treating psoriasis.

PMID- 29454235
TI  - Donor and recipient P450 gene polymorphisms influence individual pharmacological
      effects of tacrolimus in Chinese liver transplantation patients.
AB  - The immunosuppressant drug tacrolimus (Tac) used for the prevention of
      immunological rejection is a metabolic substrate of cytochrome P450 enzymes. This
      study was designed to evaluate the short-term and long-term potential influence
      of single-nucleotide polymorphisms (SNPs) in CYP450 genes of liver transplant
      (LT) recipients as well as the donors on individual pharmacological effects of
      Tac and to guide individualized-medication from the perspective of
      pharmacogenomics. Twenty-one SNPs of the CYP450 gene were genotyped for both
      recipients and donors in 373 LT patients receiving Tac-based immunosuppressants.
      The Tac concentration/dosage ratio (C/D) was evaluated from the initial
      medication until one year after LT. The C/D ratio was significantly higher when
      the donor and/or recipient genotype of CYP3A5 rs776746 was G/G or rs15524 was T/T
      or rs4646450 was C/C all through one year after transplantation. Comparing the
      effect of donor gene variants of rs776746, rs15524, and rs4646450 on Tac C/D
      ratios with the recipients, statistically significant differences were found
      between the donor T/T group and the recipient T/T group in rs15524 at 1 month and
      6 months, and at 6 months, the donor C/C group differed from the recipient C/C
      group in rs4646450. In conclusion, rs776746, rs15524, and rs4646450 of CYP3A5 had
      a significant influence on Tac pharmacological effects for both the initial use
      and long-term use. The donor liver genotype and the recipient intestine genotype
      contribute almost equally in the short-term, but the donor genotype had a greater
      effect than the recipient genotype at 6 months. Personalized Tac treatment after
      LT should be based on the CYP3A5 genotype.

PMID- 29454237
TI  - Liposomes of dimeric artesunate phospholipid: A combination of dimerization and
      self-assembly to combat malaria.
AB  - Artemisinin and its derivatives are highly effective drugs in the treatment of P.
      falciparum malaria. However, their clinical applications face challenges because
      of short half-life, poor bioavailability and growing drug resistance. In this
      article, novel dimeric artesunate phospholipid (Di-ART-GPC) based liposomes were
      developed by combination of dimerization and self-assembly to address these
      shortcomings. Firstly, Di-ART-GPC conjugate was synthesized by a facile
      esterification of artesunate (ART) and glycerophosphorylcholine (GPC) and
      confirmed by MS, 1H NMR and 13C NMR. The conjugate was then assembled to form
      liposomes without excipient by thin film hydration method. The assembled Di-ART
      GPC liposomes have typical multilamellar vesicle structure with bilayer
      morphology as determined by transmission electron microscopy (TEM) and cryogenic
      electron microscopy (cryo-EM). Moreover, the liposomes displayed an average
      hydrodynamic diameter of 190 nm and negative zeta potential at -20.35 mV as
      determined by Zetasizer. The loading capacity of ART was calculated approximately
      77.6% by weight with this liposomal formulation after a simple calculation. In
      vitro drug release and degradation results showed that the Di-ART-GPC liposomes
      were stable in neutral physiological conditions but effectively degraded to
      release parent ART in simulated weakly acidic microenvironment. In vivo
      pharmacokinetics study revealed that Di-ART-GPC liposomes and conjugate have
      longer retention half-life in bloodstream. Importantly, Di-ART-GPC liposomes
      (IC50 0.39 nM) and the conjugate (IC50 1.90 nM) demonstrated excellent in vitro
      antiplasmodial activities without causing hemolysis of erythrocytes, which were
      superior to free ART (IC50 5.17 nM) and conventional ART-loaded liposomes (IC50
      3.13 nM). Furthermore, the assembled liposomes resulted in enhanced parasites
      killing in P. berghei-infected mice in vivo with delayed recrudescence and
      improved survivability, compared to free ART administration. Based on these
      encouraging results, Di-ART-GPC liposomal formulation could be a replacement to
      parent ART in clinical malarial therapy after thorough investigation.

PMID- 29454236
TI  - STINGel: Controlled release of a cyclic dinucleotide for enhanced cancer
      immunotherapy.
AB  - Recent advancements in the field of immunotherapy have yielded encouraging
      results for the treatment of advanced cancers. Cyclic dinucleotides (CDNs) are a
      powerful new class of immunotherapy drugs known as STING (Stimulator of
      Interferon Genes) agonists, currently in clinical trials. However, previous
      studies of CDNs in murine cancer models have required multiple injections, and
      improve survival only in relatively nonaggressive tumor models. Therefore, we
      sought to improve the efficacy of CDN immunotherapy by developing a novel
      biomaterial we call "STINGel." STINGel is an injectable peptide hydrogel that
      localizes and provides controlled release of CDN delivery, showing an 8-fold
      slower release rate compared to a standard collagen hydrogel. The carrier
      hydrogel is a positively charged, MultiDomain Peptide (MDP) which self-assembles
      to form a nanofibrous matrix and is easily delivered by syringe. The highly
      localized delivery of CDN from this nanostructured biomaterial affects the local
      histological response in a subcutaneous model, and dramatically improves overall
      survival in a challenging murine model of head and neck cancer compared to CDN
      alone or CDN delivered from a collagen hydrogel. This study demonstrates the
      feasibility of biomaterial-based immunotherapy platforms like STINGel as
      strategies for increasing the efficacy of CDN immunotherapies.

PMID- 29454238
TI  - Transformations of dissolved organic matter induced by UV photolysis, Hydroxyl
      radicals, chlorine radicals, and sulfate radicals in aqueous-phase UV-Based
      advanced oxidation processes.
AB  - Considering the increasing identification of trace organic contaminants in
      natural aquatic environments, the removal of trace organic contaminants from
      water or wastewater discharge is an urgent task. Ultraviolet (UV) and UV-based
      advanced oxidation processes (AOPs), such as UV/hydrogen peroxide (UV/H2O2),
      UV/free chlorine and UV/persulfate, are attractive and promising approaches for
      the removal of these contaminants due to the high reactivity of active radical
      species produced in these UV-AOPs with a wide variety of organic contaminants.
      However, the removal efficiency of trace contaminants is greatly affected by the
      presence of background dissolved organic matter (DOM). In this study, we use
      ultrahigh resolution mass spectrometry to evaluate the transformation of a
      standard Suwanee River fulvic acid DOM isolate in UV photolysis and UV-AOPs. The
      use of probe compounds allows for the determination of the steady-state
      concentrations of active radical species in each UV-AOP. The changes in the H/C
      and O/C elemental ratios, double bond equivalents, and the low-molecular-weight
      transformation product concentrations of organic acids reveal that different DOM
      transformation patterns are induced by each UV-AOP. By comparison with the known
      reactivities of each radical species with specific organic compounds, we
      mechanistically and systematically elucidate the molecular-level DOM
      transformation pathways induced by hydroxyl, chlorine, and sulfate radicals in UV
      AOPs. We find that there is a distinct transformation in the aliphatic components
      of DOM due to HO* in UV/H2O2 and UV/free chlorine. Cl* induced transformation of
      olefinic species is also observed in the UV/free chlorine system. Transformation
      of aromatic and olefinic moieties by SO4*- are the predominant pathways in the
      UV/persulfate system.

PMID- 29454240
TI  - Deterrent effects of demerit points and license sanctions on drivers' traffic law
      violations using a proportional hazard model.
AB  - Current traffic law enforcement places an emphasis on reducing accident risk from
      human factors such as drunk driving and speeding. Among the various strategies
      implemented, demerit points and license sanction systems have been widely used as
      punitive and educational measures. Limitations, however, exist in previous
      studies in terms of estimating the interaction effects of demerit points and
      license sanctions. To overcome such limitations, this work focused on identifying
      the interaction effects of demerit points and license sanctions on driver traffic
      violation behavior. The interaction deterrent effects were assessed by using a
      Cox's proportional hazard model to provide a more accurate and unbiased
      estimation. For this purpose, five years of driver conviction data was obtained
      from the Korea National Police Agency (KNPA). This data included personal
      characteristics, demerit point accumulation and license sanction status. The
      analysis showed that accumulated demerit points had specific deterrent effects.
      Additionally, license revocation showed consistent and significant deterrent
      effects, greater than those for suspension. Male drivers under their 30s holding
      a motorcycle license were identified as the most violation-prone driver group,
      suggesting that stricter testing for the acquisition of a motorcycle driver's
      license is needed.

PMID- 29454239
TI  - Phenol separation from phenol-laden saline wastewater by membrane aromatic
      recovery system-like membrane contactor using superhydrophobic/organophilic
      electrospun PDMS/PMMA membrane.
AB  - Phenol recovery from phenol-laden saline wastewater plays an important role in
      the waste reclamation and pollution control. A membrane aromatic recovery system
      like membrane contactor (MARS-like membrane contactor) was set up in this study
      using electrospun polydimethylsiloxane/polymethyl methacrylate (PDMS/PMMA)
      membrane with 0.0048 m2 effective area to separate phenol from saline wastewater.
      Phenol and water contact angles of 0 degrees  and 162 degrees  were achieved on
      this membrane surface simultaneously, indicating its potential in the separation
      of phenol and water-soluble salt. Feed solution (500 mL) of 0.90 L/h and
      receiving solution (500 mL) of 1.26 L/h were investigated to be the optimum
      conditions for phenol separation, which corresponds to the employed Reynolds
      number of 14.6 and 20.5. During 108-h continuous separation for feed solution
      (2.0 g/L phenol, 10.0 g/L NaCl) under room temperature (20  degrees C), 42.6% of
      phenol was recycled in receiving solution with a salt rejection of 99.95%.
      Meanwhile, the mean phenol mass transfer coefficient (Kov) was 6.7 * 10-7 m s-1.
      As a membrane-based process, though the permeated phenol increased with the
      increase of phenol concentration in feed solution, the phenol recovery ratio was
      determined by the membrane properties rather than the pollutant concentrations.
      Phenol was found to permeate this membrane via adsorption, diffusion and
      desorption, and therefore, the membrane fouling generated from pore blockage in
      other membrane separation processes was totally avoided.

PMID- 29454241
TI  - Frailty and life course violence: The international mobility in aging study.
AB  - OBJECTIVE: To estimate the prevalence of frailty in older adults in the IMIAS
      population, to examine associations between lifelong domestic violence and
      frailty and possible pathways to explain these associations. METHODS: A cross
      sectional study with 2002 men and women in the International Mobility in Aging
      Study, aged between 65 and 74 years old living in five cities of Tirana
      (Albania), Natal (Brazil), Kingston and Saint-Hyacinthe (Canada), and Manizales
      (Colombia). Domestic physical and psychological violence by family and intimate
      partner was assessed by the Hurt, Insult, Threaten and Scream (HITS) scale.
      Fried's phenotype was adopted to define frailty. Logistic regressions were fitted
      to estimate between frailty and lifelong violence. Mediation analyses using the
      Preacher and Hayes method was used to examine potential health pathways. RESULTS:
      Frailty prevalence varies across cities, being lowest in Saint-Hyacinthe and
      Kingston, and highest in women in Natal. Women had a higher prevalence in Tirana
      and Natal. Adjusting for age, sex, education and research city, those reporting
      childhood physical abuse (CPA) had higher odds of frailty (OR = 1.68; 95% CI:
      1.01; 2.78); those who had been exposed to psychological violence by their
      intimate partner had also higher odds of frailty (OR = 2.07; 95% CI: 1.37; 3.12).
      CPA effect on frailty was totally mediated by chronic conditions and depression
      symptoms. Effects of psychological violence by intimate partner were partially
      mediated by chronic conditions and depression symptoms. CONCLUSIONS: Childhood
      physical abuse and psychological violence during adulthood leave marks on life
      trajectory, being conducive to adverse health outcomes and frailty in old age.

PMID- 29454242
TI  - Making space work: Staff socio-spatial practices in a paediatric outpatient
      department.
AB  - Studies of the characteristics of therapeutic landscapes have become common in
      medical geography. However, there is limited analysis of how therapeutic
      landscapes are produced. Based upon the qualitative theoretical thematic analysis
      of focus group data, this study examined the spatial work carried out by
      healthcare practitioners in a paediatric outpatients' department, turning
      unsatisfactory space into a therapeutic place. The study highlights the spatial
      strategies employed by staff to mitigate socio-spatial deficiencies in the
      healthcare environment. Staff perceived the task of making space work as an
      integral part of their duty of care to patients and an important facet of their
      professional identity. This study concludes that many of the spatial aspects of
      health care practice are often taken for granted. However this may hide the
      crucial role that health professionals have in producing places that heal.

PMID- 29454243
TI  - Health inequities faced by Ethiopian migrant domestic workers in Lebanon.
AB  - This paper investigates the healthcare needs, access to healthcare, and
      healthcare strategies of Ethiopian migrant domestic workers (MDWs) in Lebanon,
      drawing on qualitative empirical research. The analysis focusses on four types of
      health care needs: minor illnesses, pregnancies, serious illnesses (such as
      cancer, tuberculosis or heart problems), and emergencies (due to accidents,
      suicide attempts or assaults). Predictably, access to healthcare is distinctly
      differentiated according to an MDW's status as a documented, freelancer, or
      undocumented worker. Drawing on the concepts of systemic health inequities and
      inter-personal racial discrimination, the paper provides evidence for inequitable
      access to healthcare experienced by Ethiopian women in Lebanon. I identify the
      specific forms of exclusion they experience and develop a matrix for analysis of
      systemic inequities in access to healthcare differentiated by migrant status.

PMID- 29454244
TI  - 'Keeping birth normal': Exploratory evaluation of a training package for midwives
      in an inner-city, alongside midwifery unit.
AB  - OBJECTIVES: to gain understanding about how participants perceived the value and
      effectiveness of 'Keeping Birth Normal' training, barriers to implementing it in
      an along-side midwifery unit, and how the training might be enhanced in future
      iterations. DESIGN: exploratory interpretive. SETTING: inner-city maternity
      service. PARTICIPANTS: 31 midwives attending a one-day training package on one of
      three occasions. METHODS: data were collected using semi-structured observation
      of the training, a short feedback form (23/31 participants), and focus groups
      (28/31 participants). Feedback form data were analysed using summative content
      analysis, following which all data sets were pooled and thematically analysed
      using a template agreed by the researchers. FINDINGS: We identified six themes
      contributing to the workshop's effectiveness as perceived by participants. Three
      related to the workshop design: (1) balanced content, (2) sharing stories and
      strategies and (3) 'less is more.' And three related to the workshop leaders: (4)
      inspiration and influence, (5) cultural safety and (6) managing expectations.
      Cultural focus on risk and low prioritisation of normal birth were identified as
      barriers to implementing evidence-based practice supporting normal birth.
      Building a community of practice and the role of consultant midwives were
      identified as potential opportunities. KEY CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: a review of evidence, local statistics and practical skills using
      active educational approaches was important to this training. Two factors not
      directly related to content appeared equally important: catalysing a community of
      practice and the perceived power of workshop leaders to influence organisational
      systems limiting the agency of individual midwives. Cyclic, interactive training
      involving consultant midwives, senior midwives and the multidisciplinary team may
      be recommended to be most effective.

PMID- 29454245
TI  - Associations of household renovation materials and periods with childhood asthma,
      in China: A retrospective cohort study.
AB  - BACKGROUND: Childhood asthma is prevalent in China. However, there is a lack of
      evidence on whether household renovation, including the materials used and the
      periods, are associated with the disease. OBJECTIVES: To investigate the
      associations between household decoration materials and renovation periods, and
      childhood asthma and its related symptoms. METHODS: During 2010-2012, a
      retrospective cohort study was initiated in seven cities of China, and 40,010
      children, aged 3-6 years, were recruited. Data on demographics, health status,
      and home decoration conditions were collected using a parent-administered
      questionnaire. Two-level (city-child) logistic regression analyses with adjusted
      odds ratios (AORs) and 95% confidence intervals (CIs) were performed to show the
      target associations. Sensitivity analysis was performed by stratifying data for
      children in the southern and northern cities. RESULTS: Children whose homes
      underwent renovation or the addition of new furniture within 1 year before
      pregnancy, during pregnancy, at age 0-1 year, and after age 1 year had
      significantly (p < 0.05) higher prevalence of childhood asthma and its related
      symptoms. The use of solid wood floors and wallpaper had significant associations
      (cement: AOR, 95% CI: 1.59, 1.17-2.17; lime: AOR, 95% CI: 1.31, 1.00-1.71) with
      an increased risk of lifetime asthma. Household renovation and the addition of
      new furniture during pregnancy had significant associations with lifetime asthma
      (renovation: AOR, 95% CI: 1.23, 1.01-1.51); lifetime wheeze (renovation: AOR, 95%
      CI: 1.21, 1.05-1.39; furniture: AOR, 95% CI: 1.24, 1.14-1.36), current wheeze
      (renovation: AOR, 95% CI, 1.21 1.05-1.40; furniture: AOR, 95% CI: 1.23, 1.12
      1.34), and current dry cough (renovation: AOR, 95% CI: 1.41, 1.23-1.63;
      furniture: AOR, 95% CI: 1.28, 1.17-1.41). Similar associations were found between
      the addition of new furniture during early childhood and lifetime asthma and its
      related symptoms. Except for the association between lifetime wheeze and flooring
      materials, the studied associations were generally stronger among children from
      the northern cities. CONCLUSIONS: We confirmed that using cellulose based
      materials in home decoration and renovation, and adding new furniture during
      early childhood and pregnancy could be risk factors for childhood asthma. The
      association between household decoration during early childhood and childhood
      asthma may be stronger in the northern cities of China.

PMID- 29454246
TI  - Screening of physicochemical treatment processes for reducing toxicity of hair
      care products wastewaters.
AB  - Toxicity reduction in wastewaters from small hair care products manufacturing
      companies using coagulation/flocculation/sedimentation or flotation, membrane
      separation and powdered activated charcoal adsorption was evaluated. Raw
      wastewater composition varied widely within and especially between companies, but
      all exhibited high acute toxicity to Daphnia similis (EC(I)50; 48 h < 0.02
      0.33%). Coagulation with aluminum sulfate and polyaluminum chloride aided by
      cationic or anionic polymers, as well as filtration on ultra (UF) and
      nanofiltration (NF) membranes efficiently removed turbidity (>99%) and oil and
      grease (>99%) and all treated samples exhibited similar dissolved organic matter
      contents. However, elimination of acute toxicity was only achieved after UF on
      submerged hollow fiber membrane, while other membrane modules (tubular UF and NF)
      produced filtrates with residual toxicities equal to or higher than the
      wastewater samples treated by coagulation processes. Adsorption removed up to 90%
      of the soluble COD remaining after coagulation or membrane processes, but did not
      eliminate acute toxicity, possibly because of the presence of activated charcoal
      or substances leached from it in the treated samples. The results indicate the
      need for further studies to develop treatment strategies that can guarantee non
      toxic effluents at costs compatible with those of the simple manufacturing
      processes used at small-scale cosmetics manufacturing plants.

PMID- 29454247
TI  - Tolerance and growth kinetics of bacteria isolated from gold and gemstone mining
      sites in response to heavy metal concentrations.
AB  - Response and growth kinetics of microbes in contaminated medium are useful
      indices for the screening and selection of tolerant species for eco-friendly bio
      augmentative remediation of polluted environments. In this study, the heavy metal
      (HM) tolerance, bioaccumulation and growth kinetics of seven bacterial strains
      isolated from mining sites to 10 HMs (Cd, Hg, Ni, Al, Cr, Pb, Cu, Fe, Mn and Zn)
      at varied concentrations (25-600 mgL-1) were investigated. The isolates were
      phylogenetically (16S rRNA gene) related to Lysinibacillus macroides,
      Achromobacter spanius, Bacillus kochii, B. cereus, Klebsiella pneumoniae,
      Pseudomonas mosselii and P. nitroreducens. Metal tolerance, effects on lag phase
      duration and growth rates were assessed using the 96-well micro-titre method.
      Furthermore, metal bioaccumulation and quantities within cells were determined by
      transmission electron microscopy and electron dispersive x-ray analyses.
      Tolerance to Ni, Pb, Fe and Mn occurred at highest concentrations tested. Growth
      rates increased with increasing Fe concentrations, but reduced significantly (p <
      .05) with increasing Zn, Cu, Hg, Cd and Al. Significantly higher (p < .05) growth
      rates (compared to controls) was found with some isolates in Hg (25 mgL-1), Ni
      (100 mgL-1), Cr (150 mgL-1), Mn (600 mgL-1), Pb (100 mgL-1), Fe (600 mgL-1) and
      Al (50 mgL-1). Lag phase urations were isolate- and heavy metal-specific, in
      direct proportion to concentrations. A. spanius accumulated the most Mn and Zn,
      while B. cereus accumulated the most Cu. Metals accumulated intra-cellularly
      without cell morphology distortions. The isolates' multi-metal tolerance, intra
      cellular metal bioaccumulation and growth kinetics suggest potentials for
      application in the synergetic biodegradation and bioremediation of polluted
      environments, especially HM-rich sites.

PMID- 29454248
TI  - Stereocontrolled synthesis of oleanolic saponin ladyginoside A isolated from
      Ladyginia bucharica.
AB  - Efficient stereocontrolled synthesis of ladyginoside A isolated from Ladyginia
      bucharica is described. The presented methodology bases on the beta-selective
      glycosylation to construct oleanate-3-O-beta-glycoside from selectively protected
      d-cellobiose comprising desired beta-linkage in carbohydrate unit. By using this
      procedure, dimethyl ester of ladyginoside A (1) (methyl oleanate 3-O-(beta-d
      glucopyranosyl)-(1 -> 4)-beta-d-glucuronide methyl ester) was obtained in 16%
      overall yield. Elaborated synthesis is also demonstrated as useful methodology en
      route to saponin 2 with additional glucose unit, namely 3-O-[beta-d
      glucopyranosyl-(1 -> 4)-beta-d-glucuronide] oleanolic acid 28-O-beta-d
      glucopyranosyl ester.

PMID- 29454249
TI  - DFT study of electron absorption and emission spectra of pyramidal LnPc(OAc)
      complexes of some lanthanide ions in the solid state.
AB  - The electron absorption and emission spectra were measured for the pyramidal
      LnPc(OAc) complexes in the solid state and co-doped in silica glass, where Ln=Er,
      Eu and Ho. The theoretical electron spectra were determined from the quantum
      chemical DFT calculation using four approximations CAM-B3LYP/LANL2DZ, CAM
      B3LYP/CC-PVDZ, B3LYP/LANL2DZ and B3LYP/CC-PVDZ. It was shown that the best
      agreement between the calculated and experimental structural parameters and
      spectroscopic data was reached for the CAM-B3LYP/LANL2DZ model. The emission
      spectra were measured using the excitations both in the ligand and lanthanide
      absorption ranges. The possibility of energy transfer between the phthalocyanine
      ligand and excited states of lanthanide ions was discussed. It was shown that the
      back energy transfer from metal states to phthalocyanine state is responsible for
      the observed emission of the studied complexes both in the polycrystalline state
      and silica glass.

PMID- 29454250
TI  - Disulphide linkage: To get cleaved or not? Bulk and nano copper based SERS of
      cystine.
AB  - Different nano-structures of noble metals have been the conventional substrates
      for carrying out Surface Enhanced Raman Spectroscopy (SERS). In this paper we
      examine electrodeposited copper (Cu) nano-structures on pencil graphite as novel
      substrate to carry out SERS measurements by considering l-cystine (Cys-Cys)
      (dimer of the amino acid cysteine) as the probe. The formation of monolayer of
      the probe molecule on the substrates was confirmed using cyclic voltammetric
      measurements. Mode of adsorption of Cys-Cys was observed to be different on bulk
      Cu (taken in the wire form) and nano-structured Cu on pencil graphite. Whereas in
      the former the disulphide bond of Cys-Cys remained intact, it got cleaved when
      Cys-Cys was adsorbed on electrodeposited copper indicating the activated nature
      of the nano-structure compared to bulk copper. CS stretching mode of vibration
      underwent blue shift in Cys-Cys adsorbed on Cu on pencil graphite vis-a-vis Cys
      Cys adsorbed on Cu wire. Further evidence on the cleavage of the CS bond on an
      activated substrate was obtained by considering a bimetallic substrate comprising
      of silver on copper which was electrodeposited on pencil graphite. Our studies
      have demonstrated that nano-copper surface is an excellent substrate for SERS
      giving 200 MUM as lower detection limit for Cys-Cys.

PMID- 29454251
TI  - UV absorption spectrum of allene radical cations in solid argon.
AB  - Electron bombardment during deposition of an Ar matrix containing a small
      proportion of allene generated allene cations. Further irradiation of the matrix
      sample at 385 nm destroyed the allene cations and formed propyne cations in solid
      Ar. Both cations were identified according to previously reported IR absorption
      bands. Using a similar technique, we recorded the ultraviolet absorption spectrum
      of allene cations in solid Ar. The vibrationally resolved progression recorded in
      the range of 266-237 nm with intervals of about 800 cm-1 was assigned to the A2E
      <- X2E transition of allene cations, and the broad continuum absorption recorded
      in the region of 229-214 nm was assigned to their B2A1 <- X2E transition. These
      assignments were made based on the observed photolytic behavior of the
      progressions and the vertical excitation energies and oscillator strengths
      calculated using time-dependent density functional theory.

PMID- 29454252
TI  - Human papillomavirus detection using PCR and ATR-FTIR for cervical cancer
      screening.
AB  - The human papillomavirus (HPV) genital infection is considered one of the most
      common sexually transmitted diseases worldwide, and has been associated with
      cervical cancer. The objective of this study was to investigate the efficacy of
      the diagnostic methods: polymerase chain reaction (PCR) and Fourier transform
      infrared (FTIR) equipped with an ATR (Attenuated Total Reflectance) unit (Pike
      Tech) spectroscopy, to diagnose HPV infection in women undergoing gynecological
      examination. Seventeen patients (41.46%) of the 41 patients analyzed were
      diagnosed with exophytic/condyloma acuminate lesions by clinical analysis, 29
      patients (70.7%) (G1 group) of the 41 patients, showed positive result for HPV
      cell injury by oncotic colpocitology and 12 patients (29.3%) (G2 group),
      presented negative result for cellular lesion and absence of clinical HPV lesion.
      Four samples were obtained per patient, which were submitted oncotic
      colpocitology analysis (Papanicolau staining, two samples), PCR (one sample) and
      ATR-FTIR analysis (one sample). L1 gene was amplified by PCR technique with
      specific GP5+/GP6+ and MY09/MY11 primers. PCR results were uniformly positive for
      presence of HPV in all analyzed samples. Multivariate analysis of ATR-FTIR
      spectra suggests no significant biochemical changes between groups and no
      clustering formed, concurring with results of PCR. This study suggests that PCR
      and ATR-FTIR are highly sensitive technique for HPV detection.

PMID- 29454253
TI  - Charge transfer complex between 2,3-diaminopyridine with chloranilic acid.
      Synthesis, characterization and DFT, TD-DFT computational studies.
AB  - New charge transfer complex (CTC) between the electron donor 2,3-diaminopyridine
      (DAP) with the electron acceptor chloranilic (CLA) acid has been synthesized and
      characterized experimentally and theoretically using a variety of physicochemical
      techniques. The experimental work included the use of elemental analysis, UV-vis,
      IR and 1H NMR studies to characterize the complex. Electronic spectra have been
      carried out in different hydrogen bonded solvents, methanol (MeOH), acetonitrile
      (AN) and 1:1 mixture from AN-MeOH. The molecular composition of the complex was
      identified to be 1:1 from Jobs and molar ratio methods. The stability constant
      was determined using minimum-maximum absorbances method where it recorded high
      values confirming the high stability of the formed complex. The solid complex was
      prepared and characterized by elemental analysis that confirmed its formation in
      1:1 stoichiometric ratio. Both IR and NMR studies asserted the existence of
      proton and charge transfers in the formed complex. For supporting the
      experimental results, DFT computations were carried out using B3LYP/6-31G(d,p)
      method to compute the optimized structures of the reactants and complex, their
      geometrical parameters, reactivity parameters, molecular electrostatic potential
      map and frontier molecular orbitals. The analysis of DFT results strongly
      confirmed the high stability of the formed complex based on existing charge
      transfer beside proton transfer hydrogen bonding concordant with experimental
      results. The origin of electronic spectra was analyzed using TD-DFT method where
      the observed lambdamax are strongly consisted with the computed ones. TD-DFT
      showed the contributed states for various electronic transitions.

PMID- 29454254
TI  - Exploration research on synthesis and application of a new dye containing di-2
      picolyamine.
AB  - A newly designed fluorescence dye L based on di-2-picolyamine (DPA) moiety as a
      chelator was obtained under the protection of N2 at 120 degrees C, and KI as
      catalyst with relatively better yield. More interestingly, L not only could
      selectively and sensitively detect Cu2+ ions in aqueous medium but also examine
      the Cu2+ ions of the actual water samples. Nevertheless, L could be visual in
      Hela cells with excellent cell permeability, viz, monitoring exogenous Cu2+ ions
      as well as realizing an "on-off-on" process.

PMID- 29454255
TI  - Effects of adjunctive eslicarbazepine acetate on neurocognitive functioning in
      children with refractory focal-onset seizures.
AB  - PURPOSE: This was a phase-II, randomized, double-blind (DB), placebo-controlled
      study aimed to evaluate neurocognitive effects of eslicarbazepine acetate (ESL)
      as adjunctive therapy in pediatric patients with refractory focal-onset seizures
      (FOS). METHODS: Children (6-16years old) with FOS were randomized (2:1) to ESL or
      placebo. Treatment started at 10mg/kg/day, was up-titrated up to 30mg/kg/day
      (target dose), and maintained for 8weeks, followed by one-year open-label follow
      up. The primary endpoint was change from baseline to the end of maintenance
      period in the composite Power of Attention assessed with the Cognitive Drug
      Research (CDR) system. Behavioral and emotional functioning and quality of life
      (QOL), secondary endpoints, were assessed with Child Health Questionnaire-Parent
      Form 50 (CHQ-PF50), Child Behavior Checklist (CBCL), and Raven's Standard
      Progressive Matrices (SPM). Efficacy was evaluated through changes in
      standardized seizure frequency (SF), responder rate, and proportion of seizure
      free patients. Safety was evaluated by the incidence of treatment-emergent
      adverse events (TEAEs). RESULTS: One hundred and twenty-three patients were
      randomized. A noninferiority analysis failed to reject the null hypothesis that
      the change from baseline in the Power of Attention score in the ESL group was at
      least 121ms inferior to the placebo group for all age groups. The CDR scores
      showed no differences between placebo and ESL in Power of Attention (1868.0 vs
      1759.5), Continuity of Attention (1.136 vs -1.786), Quality of Working Memory (
      0.023 vs -0.024), and Speed of Memory (-263.4 vs -249.6). Nonsignificant
      differences between placebo and ESL were seen for CHQ-PF50, CBCL scores, and
      Raven's SPM. Episodic Memory Index showed significant negative effect on ESL.
      Efficacy results favored the ESL group (SF least square [LS] means 1.98 vs 4.29).
      The TEAEs had a similar incidence between treatment groups (41.0% vs 47.5%).
      CONCLUSIONS: Overall ESL did not produce statistically significant effects on
      neurocognitive and behavioral functioning in patients with epilepsy aged 6 to
      16years. Additionally, ESL was effective in reducing seizure frequency and was
      well-tolerated.

PMID- 29454256
TI  - Five-month-old infants have expectations for the accumulation of nonsolid
      substances.
AB  - Infants fail to represent quantities of non-cohesive substances in paradigms
      where they succeed with solid objects. Some investigators have interpreted these
      results as evidence that infants do not yet have representations for substances.
      More recent research, however, shows that 5-month-old infants expect objects and
      substances to behave and interact in different ways. In the present experiments,
      we test whether infants have expectations for substances when the outcomes are
      not simply the opposite of those for objects. In Experiment 1, we find that 5
      month-old infants expect that when a cup of sand pours behind a screen, it will
      accumulate in just one pile rather than two. Similarly, infants expect that when
      two cups of sand pour in separate streams, two distinct piles will accumulate
      rather than one. Infants look significantly longer at outcomes with an
      inconsistent number of piles, providing evidence that infants have expectations
      for how sand accumulates. To test whether the number of cups or the number of
      pours guided expectations about accumulation, Experiment 2 placed these cues in
      conflict. This resulted in chance performance, suggesting that, for infants to
      build expectations about these outcomes, they need both cues (cup and pour) to
      converge. These findings offer insight into the nature of infants'
      representations for non-cohesive substances like sand.

PMID- 29454257
TI  - Infants' agent individuation: It's what's on the insides that counts.
AB  - Adults and preschool-aged children believe that internal properties are more
      important than external properties when determining an agent's identity over
      time. The current study examined the developmental origins of this understanding
      using a manual-search individuation task with 13-month-old infants. Subjects
      observed semi-transparent objects that looked and behaved like animate agents
      placed into box that they could reach but not see into. Across trials infants
      observed objects with either the same- or different-colored insides placed into
      the box. We found that infants used internal property differences more than
      external property differences to determine how many agents were involved in the
      event. A second experiment confirmed that this effect was specific to the domain
      of animate entities. These results suggest that infants are biased to see an
      agent's 'insides' as more important for determining its identity over time than
      its outside properties.

PMID- 29454258
TI  - The role of dissociation in revictimization across the lifespan: A 32-year
      prospective study.
AB  - Exposure to childhood abuse puts women at risk for revictimization in adult
      intimate relationships, but knowledge about the mechanism by which it occurs is
      limited. The present study investigated whether dissociation mediates the effect
      of exposure to physical or sexual child abuse on intimate partner violence in
      adulthood. We tested this using prospective data collected from birth to age 32
      from 80 female participants in the Minnesota Longitudinal Study of Risk and
      Adaptation. We found that women who experienced sexual or physical abuse during
      the first 17.5 years of life (n = 37) were more likely (r = 0.30, p < .01) to
      experience intimate partner violence in adulthood (ages 20-32). Furthermore, we
      found that dissociation partially mediated this effect. Specifically, exposure to
      childhood abuse predicted greater dissociation in late adolescence (age 19),
      which in turn predicted more intimate partner violence during early to mid
      adulthood. The results of this study highlight the mediating role played by
      dissociation in the revictimization of women abused during childhood, and speak
      to the need to develop interventions designed to prevent intimate partner
      violence among abused girls or adult women with a history of abuse.

PMID- 29454259
TI  - The cellular mechanisms and consequences of centromere drive.
AB  - During female meiosis, only one of four meiotic products is retained in the egg.
      It was previously proposed that chromosomes might compete for inclusion in the
      egg via their centromere 'strength'. Recent findings have revealed the primary
      requirements for such 'centromere drive'. First, CDC42 signaling from the oocyte
      cortex renders the meiotic I spindle asymmetric. Second, 'stronger' centromeres
      preferentially detach from microtubules in cortical proximity, making them more
      likely to orient away from the cortex, and be included in the egg. Third,
      centromeric satellite DNA expansions result in greater recruitment of centromeric
      proteins. Despite these mechanistic insights, it is still unclear if centromere
      drive elicits rapid evolution of centromeric proteins, thereby driving cellular
      incompatibilities and wreaking havoc on centromere stability.

PMID- 29454260
TI  - Solar photo-Fenton treatment of microcystin-LR in aqueous environment:
      Transformation products and toxicity in different water matrices.
AB  - Transformation products and toxicity patterns of microcystin-LR (MC-LR), a common
      cyanotoxin in freshwaters, during degradation by solar photo-Fenton process were
      studied in the absence and presence of two major water components, namely fulvic
      acid and alkalinity. The transformation products m/z 795, 835, 515/1030 and 532
      can be formed through attack of OH on the conjugated carbon double bonds of Adda.
      Transformation products with m/z 1010, 966 and 513 can be generated through the
      attack of OH on the methoxy group of Adda. The transformation products m/z 783,
      508 and 1012 can be originated from the attack of OH on the cyclic structure of
      MC-LR. Transformation products (m/z 522, 1028, 1012, 1046 and 514) formed after
      hydroxylation of the aromatic ring with OH were also identified in this study.
      The toxicity study revealed that fulvic acid and alkalinity strongly influence
      the toxicity profiles of solar photo-Fenton treated MC-LR. Fulvic acid enhanced
      the detoxification whereas low level total alkalinity (1.8 mg L-1 CaCO3)
      inhibited the detoxification of MC-LR by solar photo-Fenton process as assessed
      by protein phosphatase-1 (PP-1) inhibition assay. This work provides insights on
      the utility of solar photo-Fenton destruction of MC-LR in water based on
      transformation products and toxicity data.

PMID- 29454262
TI  - The influence of evaluation recommendations on instrumental and conceptual uses:
      A preliminary analysis.
AB  - Evaluation recommendations are sometimes included in evaluation reports to
      highlight specific actions to be taken to improve a program or to make other
      changes to its operational context. This preliminary study sought to examine
      evaluation recommendations drawn from 25 evaluation reports published by Canadian
      federal government departments and agencies, in order to examine the evaluation
      issues covered and the focus of the recommendations. Our results show that in
      keeping with policy requirements, the evaluation recommendations focused on
      program relevance, effectiveness and efficiency and economy. Furthermore, a
      significant number of recommendations also focused on the implementation of more
      rigorous performance measurement strategies. The focus of the recommendations did
      not vary by publication date, recommendation type, and organizational sector. The
      findings also show that for the most part, the management responses produced as
      part of the broader evaluation process support the recommendations included in
      the report and identify specific timelines for implementation.

PMID- 29454263
TI  - Homeless youth: Barriers and facilitators for service referrals.
AB  - Young people who are homeless and experiencing mental health issues are reluctant
      to use relevant services for numerous reasons. Youth are also at risk of
      disengaging from services at times of referral to additional or alternative
      services. This study aimed to identify barriers and facilitators for inter
      service referrals for homeless youth with mental health issues who have already
      engaged with a service. Qualitative, semi-structured interviews were conducted
      with homeless youth (n = 10), homelessness support workers (n = 10), and mental
      health clinicians (n = 10). Barriers included: resource shortages; programs or
      services having inflexible entry criteria; complexity of service systems;
      homeless youth feeling devalued; and a lack of communication between services,
      for example, abrupt referrals with no follow up. Referral facilitators included:
      services providers offering friendly and client-centred support; supported
      referrals; awareness of other services; and collaboration between services.
      Relationships with service providers and inter-service collaboration appeared
      essential for successful referrals for homeless youth. These facilitating factors
      may be undermined by sector separation and siloing, as well as resource shortages
      in both the homelessness and mental health sectors. Service transitions may be
      conceptualised as a genuine service outcome for homeless youth, and as a basis
      for successful future service provision.

PMID- 29454261
TI  - Frequency of Somatic TP53 Mutations in Combination with Known Pathogenic
      Mutations in Colon Adenocarcinoma, Non-Small Cell Lung Carcinoma, and Gliomas as
      Identified by Next-Generation Sequencing.
AB  - The tumor suppressor gene TP53 is the most frequently mutated gene in human
      cancer. It encodes p53, a DNA-binding transcription factor that regulates
      multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis,
      and senescence. TP53 is associated with human cancer by mutations that lead to a
      loss of wild-type p53 function as well as mutations that confer alternate
      oncogenic functions that enable them to promote invasion, metastasis,
      proliferation, and cell survival. Identifying the discrete TP53 mutations in
      tumor cells may help direct therapies that are more effective. In this study, we
      identified the frequency of individual TP53 mutations in patients with colon
      adenocarcinoma (48%), non-small cell lung carcinoma (NSCLC) (36%), and
      glioma/glioblastoma (28%) at our institution using next-generation sequencing. We
      also identified the occurrence of somatic mutations in numerous actionable genes
      including BRAF, EGFR, KRAS, IDH1, and PIK3CA that occurred concurrently with
      these TP53 mutations. Of the 480 tumors examined that contained one or more
      mutations in the TP53 gene, 219 were colon adenocarcinomas, 215 were NSCLCs, and
      46 were gliomas/glioblastomas. Among the patients positive for TP53 mutations
      diagnosed with colon adenocarcinoma, 50% also showed at least one mutation in
      pathogenic genes of which 14% were BRAF, 33% were KRAS, and 3% were NRAS. Forty
      seven percent of NSCLC patients harboring TP53 mutations also had a mutation in
      at least one actionable pathogenic variant with the following frequencies: BRAF:
      4%, EGFR: 10%, KRAS: 28%, and PIK3CA: 4%. Fifty-two percent of patients diagnosed
      with glioma/glioblastoma with a positive TP53 mutation had at least one
      concurrent mutation in a known pathogenic gene of which 9% were CDKN2A, 41% were
      IDH1, and 11% were PIK3CA.

PMID- 29454264
TI  - Development and validation of UPLC-MS/MS assay for quantification of cladrin:
      Absolute bioavailability and dose proportionality study in rats.
AB  - Cladrin, an isoflavone is a major bioactive constituent found in stem bark of
      Butea monosperma with remarkable osteogenic activity. A speedy and sensitive UPLC
      coupled tandem mass spectrometry (UPLC-MS/MS) method was developed, validated and
      successfully applied to bioavailability, blood partitioning, plasma protein
      binding, intravenous and multiple-dose oral pharmacokinetics of cladrin in rats.
      Separation was done on C18 column (5.0 MUm, 4.6 * 50 mm) using mobile phase
      containing acetonitrile and 0.10% formic acid in the ratio of 65:35 (v/v) with
      0.60 mL/min flow rate. The method was highly sensitive and has a short run time
      of 2.50 min with an excellent linearity (R2 > 0.99) in the range of 0.20-200
      MUg/L. Absolute bioavailability was found to be 16.58, 19.04 and 6.76% at oral
      doses of 5, 10, and 20 mg/Kg, respectively. Cladrin was rapidly absorbed (Tmax
      3.0 h) with a high apparent volume of distribution (15.03 +/- 1.79L/Kg), high
      clearance (2.27 +/- 0.30L/h/Kg) and high plasma protein binding. The present
      study is a first comprehensive in-vitro as well as the in-vivo preclinical
      pharmacokinetic report of cladrin giving insights about its drug-likeness and
      further development as a potential therapeutic agent.

PMID- 29454265
TI  - Supplementation of lycopene attenuates lipopolysaccharide-induced amyloidogenesis
      and cognitive impairments via mediating neuroinflammation and oxidative stress.
AB  - Neuroinflammation is documented to be the major culprit of Alzheimer's disease.
      Lycopene (LYC), a fat soluble carotenoid, exhibits neuroprotective function in
      several neurodegenerative disorders. However, the effects of LYC to countering
      systemic inflammation-induced amyloidogenesis and memory deficiency remain to be
      elucidated. In current study, 3-month-old male C57BL/6J mice were treated with
      0.03% LYC (w/w, mixed into normal chow) for 5 weeks. The mice were then treated
      by intraperitoneal injection of LPS (0.25mg/kg) for 9 days. It was found that LYC
      inhibited LPS-induced memory loss by behavior tests including Y-maze test and
      Morris water test. Meanwhile, LYC prevented LPS-induced accumulation of Abeta,
      levels of amyloid precursor protein (APP), and suppressed neuronal beta-secretase
      BACE1 and elevated the expressions of alpha-secretase ADAM10. Furthermore, LYC
      down-regulated the expression of IBA-1 (a marker of microglia activation),
      reduced the levels of inflammatory mediators and inhibited oxidative stress in
      LPS-treated mice. Moreover, LYC suppressed the phosphorylation of MAPKs,
      NFkappaB, and activated Nrf2 signaling pathways in LPS-treated BV2 microglial
      cells. Therefore, our study indicated that LYC could ameliorate LPS-induced
      neuroinflammation, oxidative stress, amyloidogenesis and cognitive impairments
      possibly through mediating MAPKs, NFkappaB and Nrf2 signaling pathways,
      indicating that LYC might be a nutritional preventive strategy in
      neuroinflammation-related diseases such as AD.

PMID- 29454266
TI  - Simplified Bernoulli formula to predict flow limiting stenosis at coronary
      computed tomography angiography.
AB  - OBJECTIVE: To compare the diagnostic performance of estimated energy loss (EEL)
      with diameter stenosis (DS) to estimate significant stenosis by fractional flow
      reserve (FFR). MATERIALS AND METHODS: One hundred twenty-five patients were
      included. EEL was calculated using DS, lesion length, minimal lumen area and left
      ventricular volume. FFR <= 0.80 was determined significant. RESULTS: EEL improved
      the accuracy from 63% (95% confidence interval (CI): 55-72%) to 83% (95% CI: 75
      89%, p < 0.0001). EEL increased the area under the receiver operating
      characteristics curve from 0.63 to 0.85 (p < 0.0001). CONCLUSIONS: EEL improved
      the diagnostic performance to detect functionally significant stenosis than DS.

PMID- 29454267
TI  - Necrotizing infection of the heart.
AB  - A case of necrotizing infection of the heart is presented. A 70-year-old woman
      presented with vague chest and abdominal pain. CT of the abdomen and pelvis was
      initially obtained, which demonstrated gas in the myocardium of the left
      ventricle. Subsequent chest CT, endoscopy, and abdominal surgical exploration did
      not reveal perforated viscus or diaphragm compromise. At median sternotomy, the
      inferior wall of the heart was found to be necrotic. Culture of the excised
      tissue grew E. coli. The patient expired shortly after surgical exploration.

PMID- 29454268
TI  - Occurrence and distribution of antibiotics in mariculture farms, estuaries and
      the coast of the Beibu Gulf, China: Bioconcentration and diet safety of seafood.
AB  - The occurrence, distribution, bioconcentration and diet safety via seafood
      consumption of 19 antibiotics were investigated in eight closed mariculture
      ponds, four estuaries, two nearshore areas and one offshore area from the Beibu
      Gulf. Seventeen, 16, 15 and 7 antibiotics were detected at total concentrations
      of 43.2 - 885 ng L-1, 22.4 - 118 ng L-1, 22.7 - 24.5 ng L-1, and 1.81-3.23 ng L-1
      in the water of the above different areas, respectively. This indicates that the
      mariculture ponds are important sources of antibiotic pollution on the coast of
      the Beibu Gulf. Ten antibiotics were detected in feed samples with concentrations
      ranging from 0.03 to 95.4 ng g-1, demonstrating the presence of antibiotics in
      the feed and/or residual antibiotics in the raw material of the feed. The field
      bioconcentration factors (BCFs) of the antibiotics calculated in different
      culture organisms ranged from 0.55 to 10,774 L kg-1. The estimated daily intakes
      (EDIs) of sulphonamides, fluoroquinolones, macrolides and chloramphenicols via
      aquatic products were 19.8-105, 33.7-178, 34.9-186 and 6.9-37.1 ng d-1,
      respectively. According to the acceptable daily intakes (ADIs) and maximum
      residue limits (MRLs) proposed by different organisations, these aquatic products
      (shrimp, crab and oyster) reached the standard of safe consumption and could not
      pose a health risk to humans. However, a potential elevated risk to humans may
      remain because of the occurrence of multiple antibiotics in the cultured
      organisms, particularly for sensitive populations, such as pregnant women, the
      elderly and children.

PMID- 29454269
TI  - Biological effects of four iron-containing nanoremediation materials on the green
      alga Chlamydomonas sp.
AB  - As nanoremediation strategies for in-situ groundwater treatment extend beyond
      nanoiron-based applications to adsorption and oxidation, ecotoxicological
      evaluations of newly developed materials are required. The biological effects of
      four new materials with different iron (Fe) speciations ([i] FerMEG12 - pristine
      flake-like milled Fe(0) nanoparticles (nZVI), [ii] Carbo-Iron(r) - Fe(0)
      nanoclusters containing activated carbon (AC) composite, [iii] Trap-Ox(r) Fe
      BEA35 (Fe-zeolite) - Fe-doped zeolite, and [iv] Nano-Goethite - 'pure' FeOOH)
      were studied using the unicellular green alga Chlamydomonas sp. as a model test
      system. Algal growth rate, chlorophyll fluorescence, efficiency of photosystem
      II, membrane integrity and reactive oxygen species (ROS) generation were assessed
      following exposure to 10, 50 and 500 mg L-1 of the particles for 2 h and 24 h.
      The particles had a concentration-, material- and time-dependent effect on
      Chlamydomonas sp., with increased algal growth rate after 24 h. Conversely,
      significant intracellular ROS levels were detected after 2 h, with much lower
      levels after 24 h. All Fe-nanomaterials displayed similar Z-average sizes and
      zeta-potentials at 2 h and 24 h. Effects on Chlamydomonas sp. decreased in the
      order FerMEG12 > Carbo-Iron(r) > Fe-zeolite > Nano-Goethite. Ecotoxicological
      studies were challenged due to some particle properties, i.e. dark colour, effect
      of constituents and a tendency to agglomerate, especially at high concentrations.
      All particles exhibited potential to induce significant toxicity at high
      concentrations (500 mg L-1), though such concentrations would rapidly decrease to
      mg or ug L-1 in aquatic environments, levels harmless to Chlamydomonas sp. The
      presented findings contribute to the practical usage of particle-based
      nanoremediation in environmental restoration.

PMID- 29454270
TI  - Cadmium-induced stress response of Phanerochaete chrysosporium during the
      biodegradation of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47).
AB  - Cd-induced stress response of Phanerochaete chrysosporium during the
      biodegradation of BDE-47 was investigated in this study, with the goal of
      elucidating the tolerance behavior and the detoxification mechanisms of P.
      chrysosporium to resist the Cd stress in the course of BDE-47 biodegradation,
      which has implications for expanding the application of P. chrysosporium in the
      bioremediation of Cd and BDE-47 combined pollution. The results suggested that
      single BDE-47 exposure did not induce obvious oxidative stress in P.
      chrysosporium, but coexistent Cd significantly triggered ROS generation, both
      intracellular ROS level and H2O2 content showed positive correlation with Cd
      concentration. The activities of SOD and CAT were enhanced by low level of Cd (<=
      1 mg/L), but Cd of higher doses (>1 mg/L) depressed the expression of these two
      antioxidant enzymes at the later exposure period (3-5 days). The intracellular
      content of GSH along with GSH/GSSG ratio also exhibited a bell-shaped response
      with a maximum value at Cd of 1 mg/L. Furthermore, Cd-induced ROS generation
      resulted in the lipid peroxidation, as indicated by a noticeable increment of MDA
      content found after 3 days. Moreover, the study also indicated that Cd less than
      1 mg/L promoted the production of extracellular protein and quickened the
      decrease of pH value in the medium, while excessive Cd (>1 mg/L) would lead to
      inhibition. These findings obtained demonstrated that P. chrysosporium had a
      certain degree of tolerance to Cd within a specific concentration range via
      regulating the antioxidant levels, inducing the synthesis of extracellular
      protein as well as stimulating the production of organic acids, and 1 mg/L is
      suggested to be the tolerance threshold of this strains under Cd stress during
      BDE-47 biodegradation.

PMID- 29454271
TI  - The complexation of rhizosphere and nonrhizosphere soil organic matter with
      chromium: Using elemental analysis combined with FTIR spectroscopy.
AB  - Complexation is a main mechanism controlling the reactions between soil organic
      matter (SOM) and heavy metals, which still have not been fully understood up to
      date. The objective of this study was to compare the SOM composition of
      nonrhizosphere and rhizosphere in low Cr treatment with that in high Cr treatment
      and to find out how metal concentrations affect the complexation with SOM. The
      results revealed that both the hydroxyl and the carboxyl were significantly
      different under different Cr treatment groups. For nonrhizosphere samples, the
      high Cr treatment tended to have less hydroxyl contents and more structural
      changes on hydroxyl (3389-3381 cm-1) than the low Cr treatment (3389-3388 cm-1),
      while in the rhizosphere samples the reverse happened. The gap of the different
      Cr treated band area in the rhizosphere samples (44 a.u of the gap) was greatly
      smaller than that in the nonrhizosphere samples (576 a.u of the gap). In both the
      rhizosphere and nonrhizosphere samples, the high Cr treatment showed greater
      structural changes on carboxylic acids (11, 12 a.u changes based on the control)
      than the low Cr treatment (4, 6 a.u). The unsaturated carboxylic acids could
      account for downward frequency shift and the contents in the nonrhizosphere
      samples were slightly greater than that in the rhizosphere samples. This study
      used elemental analysis combined with FTIR spectroscopy to explore the effects of
      metal concentrations on the complexation of Cr with SOM and the composition of
      SOM. These findings give a way to understanding part of the complexation
      mechanisms between the metal and SOM.

PMID- 29454272
TI  - Dealing with the nucleus during cell migration.
AB  - The position of the nucleus within cells is a key event during cell migration.
      The movement and positioning of the nucleus strongly impacts cell migration.
      Notably, the last two years largely contributed to emphasise the dynamicity of
      the nucleus-cytoskeleton interactions that occur during cell migration. Nuclei
      are under continuous tension from opposing intracellular forces and its tether to
      the cytoskeleton can be regulated at different levels. Interestingly, it was
      showed how nuclear positioning is highly related to cell function. In most
      migrating cells, including cancer cells, the nucleus can be the rate limiting
      step of cell migration and is placed away from the leading edge. By contrast,
      leukocytes position their nucleus close to the lamellipodia at the leading edge,
      and the nucleus contributes to drilling through the endothelium. Differences in
      cell migration in 2D versus 3D environments are also evident. The mechanisms and
      forces at play during nuclear positioning and translocation are clearly affected
      by the nature of the substrate. As such nuclear positioning during cell migration
      can vary between cell types and environments. In this review we aim to give an
      overview of the latest discoveries in the field revealing how nuclear positioning
      is tightly regulated, not only by intrinsic nuclear properties, such as
      deformability, nuclear envelope content or nucleus-cytoskeleton connectivity, but
      also by the microenvironment.

PMID- 29454273
TI  - Mechanosensitive adhesion complexes in epithelial architecture and cancer onset.
AB  - Mechanical signals from the extracellular space are paramount to coordinate
      tissue morphogenesis and homeostasis. Although there is a wide variety of
      cellular mechanisms involved in transducing extracellular forces, recent
      literature emphasizes the central role of two main adhesion complexes in
      epithelial mechanosensitive processes: focal adhesions and adherens junctions.
      These biomechanical sensors can decode physical signals such as matrix stiffness
      or intercellular tension into a wide range of coordinated cellular responses,
      which can impact cell differentiation, migration, and proliferation.
      Communication between cells and their microenvironment plays a pivotal role both
      in physiological and pathological conditions. Here we summarize the most recent
      findings on the biology of these mechanotransduction pathways in epithelial
      cells, highlighting the extensive amount of biological processes coordinated by
      cell-matrix and cell-cell adhesion complexes.

PMID- 29454274
TI  - A multifaceted coating on titanium dictates osteoimmunomodulation and osteo/angio
      genesis towards ameliorative osseointegration.
AB  - A multifaceted coating for hard tissue implants, with favorable osteogenesis,
      angiogenesis, and osteoimmunomodulation abilities, would be of great value since
      it could improve osseointegration and alleviate prosthesis loosening. However, to
      date there are few coatings that fully satisfy these criteria. Herein we describe
      a microporous TiO2 coating decorated with hydroxyapatite (HA) nanoparticles that
      is generated by micro-arc oxidation of pure titanium (Ti) and followed annealing.
      By altering the annealing temperature, it is possible to simultaneously tune the
      coating's physical (morphology and wettability) and chemical (composites and
      crystallinity) properties. A coating produced with micro-arc oxidization (MAO)
      with an annealing temperature of 650  degrees C (MAO-650) exhibits numerous
      favorable physicochemical properties, such as hybrid micro-nano morphology,
      superhydrophilicity, and highly crystalline HA nanoparticles. In vitro
      experiments reveal that the MAO-650 coating not only supports proliferation and
      differentiation of both osteoblasts and endothelial cells, but also inhibits the
      inflammatory response of macrophages and enables a favorable
      osteoimmunomodulation to facilitate osteo/angio-genesis. In vivo evaluation
      mirrors these results, and shows that the MAO-650 coating results in ameliorative
      osseointegration when compared with the pristine MAO coating. These data
      highlight the profound effect of surface physicochemical properties on the
      regulation of osteo/angio-genesis and osteoimmunomodulation in the enhancement of
      osseointegration.

PMID- 29454275
TI  - Long-term follow-up of patients undergoing tibialis posterior transfer: Is
      acquired pes planus a complication?
AB  - In this retrospective study, a series of 10 elective patients treated with
      transfer of the tibialis posterior (TP) tendon for pes cavus and drop foot are
      described. Since TP transfer completely subtracts the role of this tendon, this
      cohort of patients provides an opportunity to examine the consequences of
      tibialis posterior (TP) deficiency. After a mean follow up period of 44.7 months,
      only one patient showed evidence of strain in the spring ligament but none of the
      patients in this series developed clinical or radiological evidence of
      planovalgus deformity. The authors conclude that planovalgus deformity is not an
      inevitable sequelae of TP Tendon transfer and that established theory
      underestimates the role of static soft tissue restraints such as spring ligament
      in hindfoot stability.

PMID- 29454276
TI  - Use of mixed wastewaters from piggery and winery for nutrient removal and lipid
      production by Chlorella sp. MM3.
AB  - The larger-scale generation of piggery and winery wastewaters and consequent
      eutrophication are quite alarming, necessitating the use of a cost-effective
      treatment. This study attempted to remediate wastewaters from piggery and winery
      mixed in the ratios of 20:80, 50:50, 80:20, 100:0 and 0:100, in terms of nutrient
      removal and subsequent lipid accumulation by soil microalga, Chlorella sp. MM3.
      The per cent removal of total nitrogen and phosphates by the alga from mixed
      wastewaters within 10-days ranged between 51 and 89 and 26-49, respectively. As
      determined by FTIR spectroscopy, the lipid accumulation in the microalgal cells
      grown in wastewater mixtures ranged between 29 and 51%. Our results suggest that
      Chlorella sp. MM3 could be a potential candidate for bioremediation of
      wastewaters derived from piggery farm and winery industry, and that mixing of
      these wastewaters in 20:80 ratio would be an efficient approach for
      phycoremediation of mineral-rich effluents and subsequent yield of fairly good
      amounts of biofuel.

PMID- 29454277
TI  - Nitrogen removal enhancement using lactic acid fermentation products from food
      waste as external carbon sources: Performance and microbial communities.
AB  - In this study, nitrogen removal using the lactic acid fermentation products from
      food waste and other external chemical carbon sources (sodium acetate, sodium
      lactate and starch) was investigated. Similar to sodium acetate and lactate, the
      lactic acid-enriched fermentation liquid from food waste (FLFW) exhibited a high
      denitrification rate (5.5 mg NOx-N/(g-VSS h)) and potential (0.16 g NO3--N/g
      COD), and could achieve high NH4+-N and total nitrogen (TN) removal efficiencies
      during long-term operation. Using FLFW as supplementary carbon sources reduced
      the extracellular polymeric substances (EPS) content, improved the settleability
      and achieved a satisfactory biomass yield of activated sludge. Additionally, the
      increased microbial metabolic activity and bacterial community diversity and the
      accumulation of unique bacteria in the activated sludge cultured with FLFW
      further promoted the organics utilization rate and nitrogen removal efficiency,
      indicating that the FLFW prepared from solid waste was an ideal carbon source for
      wastewater treatment.

PMID- 29454278
TI  - Towards a better understanding on mercury adsorption by magnetic bio-adsorbents
      with gamma-Fe2O3 from pinewood sawdust derived hydrochar: Influence of atmosphere
      in heat treatment.
AB  - Pyrolysis under protective atmosphere was regarded as an indispensable process
      for the preparation of biomass-based adsorbents to achieve higher surface areas.
      In this paper, magnetic carbon composites (MCC) that fabricated under air
      atmosphere showed an adsorption capacity of 167.22 mg/g in 200 ppm Hg(II), which
      was significantly higher than magnetic biochar (MBC, 31.80 mg/g) that fabricated
      under traditional nitrogen protection, and this remarkable performance of MCC was
      consistent in a wide range of pHs. Based on BET, XRD, FTIR, SEM and Boehm
      titration, MCC was demonstrated with limited surface area (43.29 m2/g) but large
      amount of surface functional groups comparing with MBC. Additionally, gamma-Fe2O3
      with a high degree of crystallization was generated in MCC, which led to a better
      magnetic property and recyclability. Moreover, characterizations, Langmuir
      isotherm and pseudo-second-order kinetics demonstrated the chemisorption was
      dominant for MCC in mercury capture, and surface complexation co-precipitate of
      Hg4Fe8O16C56H40 were also formed.

PMID- 29454279
TI  - Bonding of composite cements to zirconia: A systematic review and meta-analysis
      of in vitro studies.
AB  - OBJECTIVES: The aim of this study was to systematically review the literature and
      statistically analyze bond strength data to identify the influence that composite
      cements, type of test methodology, chemical and mechanical pre-treatments have on
      the bond strength of composite cements to zirconia in three different artificial
      aging conditions. METHODS: The literature was electronically searched in MEDLINE,
      PUBMED, EMBASE, and SCOPUS to select relevant articles that evaluated the bond
      strength between zirconia and composite cements. A manual search was performed by
      scanning the reference lists of included studies. All articles were published
      online before December 2016 and in English. From electronic database and manual
      searches, 444 studies were identified; 161 articles with 1632 test results met
      the inclusion criteria. Test results were assigned into 3 aging conditions: non
      aged, intermediate-aged and aged groups. Generalized estimating equations (GEE)
      were used to explore actual mean bond strengths. As the bond strength is a non
      negative value, lognormal distribution was used. RESULTS: In non-aged condition,
      data showed statistically significant interactions between cement type and type
      of test. There was no statistically significant interaction between mechanical
      and chemical pre-treatments. In intermediate-aged and aged conditions, data
      showed no statistically significant interactions between mechanical and chemical
      pre-treatments and between cement type and type of test. CONCLUSIONS: This meta
      analysis appeared to indicate that mechanical pre-treatments, and in particular
      ceramic coating, combined with methacryloyloxydecyl dihydrogen phosphate (MDP)
      containing primers yielded the highest long-term bond strength (aged-condition).
      However, data are limited and caution should be exercised before applying these
      results to clinical situations.

PMID- 29454280
TI  - 8-Chrysoeriol, as a potential BCL-2 inhibitor triggers apoptosis of SW1990
      pancreatic cancer cells.
AB  - 8-Chrysoeriol, a bioactive flavanoid, was firstly identified to bind directly to
      BCL-2 as BH3 mimetics by structure-based virtual ligand screening. And 3D docking
      model revealed the molecular basis of 8-Chrysoeriol targeting to BCL-2. The
      interaction between 8-Chrysoeriol and BCL-2 was further confirmed using
      Microscale Thermophoresis (MST) technique. Meanwhile, high expression level of
      antiapoptotic protein BCL-2 was detected in SW1990 pancreatic cancer cells and 8
      Chrysoeriol showed obvious proapoptosis effect against SW1990 in vitro.
      Collectively, the results showed that 8-Chrysoeriol as a natural dietary product
      potentially targeting to BCL-2 could serve as a lead compound for SW1990
      pancreatic cancer therapy.

PMID- 29454281
TI  - Probing the beta-pocket of the active site of human liver glycogen phosphorylase
      with 3-(C-beta-d-glucopyranosyl)-5-(4-substituted-phenyl)-1, 2, 4-triazole
      inhibitors.
AB  - Human liver glycogen phosphorylase (hlGP), a key enzyme in glycogen metabolism,
      is a valid pharmaceutical target for the development of new anti-hyperglycaemic
      agents for type 2 diabetes. Inhibitor discovery studies have focused on the
      active site and in particular on glucopyranose based compounds with a beta-1
      substituent long enough to exploit interactions with a cavity adjacent to the
      active site, termed the beta-pocket. Recently, C-beta-d-glucopyranosyl imidazoles
      and 1, 2, 4-triazoles proved to be the best known glucose derived inhibitors of
      hlGP. Here we probe the beta-pocket by studying the inhibitory effect of six
      different groups at the para position of 3-(beta-d-glucopyranosyl phenyl)-5
      phenyl-, 1, 2, 4-triazoles in hlGP by kinetics and X-ray crystallography. The
      most bioactive compound was the one with an amine substituent to show a Ki value
      of 0.43 MUM. Structural studies have revealed the physicochemical diversity of
      the beta-pocket providing information for future rational inhibitor design
      studies.

PMID- 29454282
TI  - Contaminants of emerging concern presence and adverse effects in fish: A case
      study in the Laurentian Great Lakes.
AB  - The Laurentian Great Lakes are a valuable natural resource that is affected by
      contaminants of emerging concern (CECs), including sex steroid hormones, personal
      care products, pharmaceuticals, industrial chemicals, and new generation
      pesticides. However, little is known about the fate and biological effects of
      CECs in tributaries to the Great Lakes. In the current study, 16 sites on three
      rivers in the Great Lakes basin (Fox, Cuyahoga, and Raquette Rivers) were
      assessed for CEC presence using polar organic chemical integrative samplers
      (POCIS) and grab water samplers. Biological activity was assessed through a
      combination of in vitro bioassays (focused on estrogenic activity) and in vivo
      assays with larval fathead minnows. In addition, resident sunfish, largemouth
      bass, and white suckers were assessed for changes in biological endpoints
      associated with CEC exposure. CECs were present in all water samples and POCIS
      extracts. A total of 111 and 97 chemicals were detected in at least one water
      sample and POCIS extract, respectively. Known estrogenic chemicals were detected
      in water samples at all 16 sites and in POCIS extracts at 13 sites. Most sites
      elicited estrogenic activity in bioassays. Ranking sites and rivers based on
      water chemistry, POCIS chemistry, or total in vitro estrogenicity produced
      comparable patterns with the Cuyahoga River ranking as most and the Raquette
      River as least affected by CECs. Changes in biological responses grouped
      according to physiological processes, and differed between species but not sex.
      The Fox and Cuyahoga Rivers often had significantly different patterns in
      biological response Our study supports the need for multiple lines of evidence
      and provides a framework to assess CEC presence and effects in fish in the
      Laurentian Great Lakes basin.

PMID- 29454283
TI  - Investigating antibiotics, antibiotic resistance genes, and microbial
      contaminants in groundwater in relation to the proximity of urban areas.
AB  - Groundwater is an essential public and drinking water supply and its protection
      is a goal for global policies. Here, we investigated the presence and prevalence
      of antibiotic residues, antibiotic resistance genes (ARGs), mobile genetic
      elements (MGEs), and microbial contamination in groundwater environments at
      various distances from urban areas. Antibiotic concentrations ranged from below
      detection limit to 917 ng/L, being trimethoprim, macrolide, and sulfonamide the
      most abundant antibiotic classes. A total of eleven ARGs (aminoglycoside, beta
      lactam, chloramphenicol, Macrolide-Lincosamide-Streptogramin B - MLSB,
      sulfonamide, and tetracycline), one antiseptic resistance gene, and two MGEs were
      detected by qPCR with relative abundances ranging from 6.61 * 10-7 to 2.30 * 10-1
      copies/16S rRNA gene copies. ARGs and MGEs were widespread in the investigated
      groundwater environments, with increased abundances not only in urban, but also
      in remote areas. Distinct bacterial community profiles were observed, with a
      higher prevalence of Betaproteobacteria and Bacteroidetes in the less-impacted
      areas, and that of Firmicutes in the contaminated groundwater. The combined
      characteristics of increased species diversity, distinct phylogenetic
      composition, and the possible presence of fecal and/or pathogenic bacteria could
      indicate different types of contamination. Significant correlations between ARGs,
      MGEs and specific taxa within the groundwater bacterial community were
      identified, revealing the potential hosts of resistance types. Although no
      universal marker gene could be determined, a co-selection of int1, qacEDelta1 and
      sulI genes, a proxy group for anthropogenic pollution, with the tetC, tetO, tetW
      resistance genes was identified. As the tet group was observed to follow the
      pattern of environmental contamination for the groundwater samples investigated
      in this study, our results strongly support the proposal of this group of genes
      as an environmental tracer of human impact. Overall, the present study
      investigated several emerging contaminants in groundwater habitats that may be
      included in monitoring programs to enable further regulatory and protection
      measures.

PMID- 29454284
TI  - The provision of specialist psychosocial support for people with visible
      differences: A European survey.
AB  - A substantial body of research has demonstrated the challenges commonly facing
      people with visible differences (disfigurements) and explored the potential
      benefits offered by specialist psychosocial support and intervention for those
      who are negatively affected. However, little is known about the availability of
      such support in Europe for people whose appearance is in any way different to
      'the norm'. This survey of 116 psychosocial specialists from 15 European
      countries, working with a range of patient groups, has shown a tendency for
      specialists to prioritise Cognitive-behavioural-based approaches, amongst a wide
      range of other approaches and interventional techniques. It indicates variations
      in the availability of support, and a perceived need for improved access to
      interventions, additional training, and greater awareness of the psychosocial
      issues associated with visible differences.

PMID- 29454285
TI  - POU5F1B promotes hepatocellular carcinoma proliferation by activating AKT.
AB  - Hepatocellular carcinoma (HCC) is one of the most common tumors, so far, there
      still aren't good therapeutic methods. Looking for new targets makes a top
      priority. In this study, we found a OCT4 pseudogene, POU5F1B was significantly
      upregulated in HCC cells and tissues, patients with high POU5F1B had shorter
      survival time compared to patients with low POU5F1B expression. POU5F1B
      overexpression promoted HCC proliferation, while its knockdown inhibited HCC
      proliferation determined by MTT assay, soft agar growth assay, BrdU incorporation
      assay, and cell cycle assay. Mechanism analysis suggested POU5F1B could activate
      AKT, AKT inhibition in HCC cells with POU5F1B overexpression significantly
      inhibited cell proliferation compared to cells only with POU5F1B overexpression,
      suggesting POU5F1B promoted HCC proliferation by activating AKT. Finally, we
      analyzed the relationship between POU5F1B expression and AKT activity in HCC
      tissues, and found POU5F1B expression was positive correlated with activated AKT.
      Taken together, our findings suggested POU5F1B promoted HCC proliferation by
      activating AKT, and provided a new target for HCC therapy.

PMID- 29454286
TI  - The vasodilatory effect of allopurinol mediates its antihypertensive effect:
      Effects on calcium movement and cardiac hemodynamics.
AB  - Despite the reported reduction in blood pressure in hypertensive patients treated
      with allopurinol, the mechanism of the allopurinol hypotensive effect is still
      unclear. In the current study, the hypotensive effect of allopurinol has been
      fully investigated in hypertensive rats. Hypertension was induced in rats by
      angiotensin II (120 ng/min/kg) infusion for two weeks. Rats were then subjected
      to real-time recording of blood pressure, left ventricular pressure and volume
      and surface ECG. After 10 min of basal recording, allopurinol was slowly injected
      into the femoral vein with a dose of 10 MUmole/kg. Then, invasive blood pressure,
      cardiac hemodynamics and ECG were continuously recorded for an additional 20 min.
      In addition, the vasodilation effect of allopurinol was studied using the
      isolated artery technique. Allopurinol injection reduced systolic, diastolic and
      pulse blood pressure. Allopurinol suppressed both cardiac systolic and diastolic
      hemodynamics as is apparent from the reduction in the rate of rise and the rate
      of fall in left ventricular pressure. Allopurinol reduced the general cardiac
      output quickly. Allopurinol addition to the organ bath (10-1000 MUM) produced
      significant vasodilation of PE pre-constricted aortae that was not affected by
      endothelium denudation, L-NAME or indomethacin. However, allopurinol ameliorated
      the calcium induced contraction of aorta pre-constricted with KCl in calcium-free
      media. Erk or ROCK inhibition did not attenuated allopurinol produced
      vasodilation. In conclusion, allopurinol has an antihypertensive effect that is
      mediated, probably, by reducing cardiac output and decreasing vascular
      resistance. The vasodilator effect of allopurinol is most likely mediated by
      calcium blocking activities.

PMID- 29454287
TI  - The sedative activity of flavonoids from Passiflora quadrangularis is mediated
      through the GABAergic pathway.
AB  - The aim of this study was to investigate the sedative activity of the aqueous
      leaf extract of Passiflora quadrangularis, a species that is widely cultivated
      and consumed in South America, and to identify its main constituents and
      elucidate the involvement of the GABAergic pathway in its mechanism of action.
      The bioguided fractionation of the crude extract showed a positive relationship
      between the sedative activity of the extract and its flavonoids. The methods
      employed to identify and isolate its main flavonoids resulted in the
      identification of vitexin-2''-O-xyloside, vitexin-2''-O-glucoside, orientin-2''-O
      xyloside and orientin-2''-O-glucoside. Vitexin-2"-O-xyloside, the major flavonoid
      of the extract, showed sedative activity after oral administration in mice.

PMID- 29454288
TI  - Apocynum venetum leaf extract reverses depressive-like behaviors in chronically
      stressed rats by inhibiting oxidative stress and apoptosis.
AB  - BACKGROUND: Major depressive disorder (MDD) is a common but serious psychiatric
      disorder, but current treatments are inadequate for approximately half of the
      patients with MDD. Thus, better methods of treatment are urgently needed. This
      study aimed to investigate the antidepressant-like effects and potential
      mechanism of Apocynum venetum leaf extract (AVLE) in chronic unpredictable mild
      stress (CUMS) rat model of depression. MATERIALS AND METHODS: The CUMS rat model
      of depression was used to investigate the antidepressant-like activity and
      relevant mechanism of AVLE (30, 60, and 125 mg/kg, i.g.). Behavioral tests,
      including sucrose preference test (SPT), open field test (OFT), and forced
      swimming test (FST) were conducted to assess anhedonic, despairing, and
      spontaneous behaviors, respectively. The activity of the hypothalamic-pituitary
      adrenal (HPA) axis was evaluated by measuring the serum adrenocorticotrophic
      hormone (ACTH) and corticosterone (CORT) concentrations. The underlying mechanism
      was further explored by assessing oxidative stress parameters, cell apoptosis,
      and brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus
      exposed to CUMS. RESULTS: The AVLE (36, 60, 125 mg/kg) treatment exerted
      antidepressant-like effects in CUMS-exposed rats similar to fluoxetine (10
      mg/kg). The AVLE treatment reduced the serum CORT and ACTH levels in CUMS rats.
      It also increased the activities and gene expression of antioxidant enzymes (SOD,
      CAT, and GPx) and decreased the ROS generation levels and the lipid peroxidation
      marker MDA in the rat hippocampus subjected to CUMS. Additionally, it suppressed
      the apoptosis of hippocampus cells by modulating Bcl-2/Bax pathways and improved
      the hippocampal BDNF expressions of CUMS rats. CONCLUSION: Our findings suggested
      that AVLE exerted antidepressant-like effects in CUMS rats, which was possibly
      mediated by the prevention of oxidative stress, the inhibition of hippocampal
      neuronal apoptosis, and the upregulation of the hippocampal BDNF level.

PMID- 29454289
TI  - Walking speed measurement with an Ambient Measurement System (AMS) in patients
      with multiple sclerosis and walking impairment.
AB  - BACKGROUND: Walking speed is an important measure of gait impairment in multiple
      sclerosis (MS). The clinical assessment of walking speed requires dedicated time,
      space, and personnel, and may not accurately gauge real-world performance. The
      term "Ambient Measurement System" (AMS) refers to a new class of device that
      passively measures walking speed at home, without the need for dedicated space or
      specialized setup. This study compared an AMS, Echo5D, versus in-clinic standard
      measures of walking speed on a straight path. METHODS: Twenty participants with
      MS and walking impairment were recruited from the Cleveland Clinic Mellen Center
      for MS. Each participant traversed an electronic GAITRite CIRFace (GC) sensor mat
      four times (two at comfortable pace, two at fast pace). Each participant then
      performed the Timed 25-Foot Walk (T25FW) twice, measured by a manual stopwatch
      (SW). All traversals were simultaneously measured by an array of Echo5D devices.
      Echo5D speeds were correlated with the Patient-Determined Disease Steps and the
      MS Walking Scale-12 patient-reported outcomes. RESULTS: Pearson correlations
      between Echo5D and clinical tests ranged from 0.89 to 0.98 (p < 0.0001). No
      statistically significant bias was found between Echo5D and GC. A small
      statistically significant bias was found between Echo5D and SW, with Echo5D
      reporting approximately 5% faster walking speeds in aggregate. CONCLUSIONS: Among
      MS patients with walking impairments, the Echo5D AMS acquired walking speeds
      which were closely correlated with the standard measures of GC and SW. The strong
      agreement supports the use of Echo5D to assess in-home, real-world walking
      performance in MS.

PMID- 29454290
TI  - Ligand-based computer aided drug design reveals new tropomycin receptor kinase a
      (TrkA) inhibitors.
AB  - Targeting tropomycin kinase A (TrkA) by small molecule inhibitors is considered
      as a promising strategy for treating several human cancers. To achieve this goal,
      a ligand based QSAR model was applied using the Discovery studio 4.5 (DS 4.5).
      Hence, a total list of 161 TrkA inhibitors was investigated. The TrkA inhibitors
      were extensively explored to detect their optimal physicochemical properties and
      pharmacophoric binding modes, which were converted into numeric descriptors and
      allowed to compete within the context of the Genetic Function Algorithm (GFA)
      approximations to find the subset of terms that correlates best with the
      activity. The resulted successful QSAR equation had statistical criteria of
      (r2129=0.67, r2LOO=0.61 r2PRESS against 32 external test inhibitors=0.50).
      Afterwards, the most successful pharmacophore: HypoB-T5-3, was used to screen
      compounds within the National Cancer institute (NCI) database. Only 41 compounds
      were retrieved and 21 of them exhibited anti-TrkA activity. The most potent hit
      had an IC50 value of 2.4MUM. Later, upon docking the active hits into the TrkA
      binding pocket, important interactions were revealed including hydrogen bonding
      with the amino acids Asp668 and Lys544 in addition to the cation-pi interactions
      with the sidechain of Arg559.

PMID- 29454291
TI  - De novo transcriptome of the pallial gland of the date mussel (Lithophaga
      lithophaga).
AB  - Lithophaga lithophaga is a rock-boring bivalve with an ability to dissolve
      carbonate substrata with its siphonal and pallial gland secretions. However, the
      molecular mechanism that enables this species to bore into calcareous rocks is
      not yet known. In order to identify genes potentially involved in chemical boring
      we performed transcriptome sequencing of pallial-gland tissue samples of L.
      lithophaga. Transcriptome sequencing using an Ion Torrent platform generated
      60.563 million clean reads with an average read length of 96 bp. De novo assembly
      of clean reads produced 62,490 contigs with a mean length of 408 bp. Since the
      boring mechanism is attributed to calcium-binding proteins, the search focused on
      transcripts capable of binding this element. In all, 178 genes with calcium
      binding ability were found to be expressed in the pallial gland of L. lithophaga.
      Annexins, calreticulin, phospholipase A2 and V-type proton-ATPases were
      considered as possible candidate chemical-boring genes due to their known
      function and involvement in various other biological processes: e.g. ion
      transport, cellular catabolic process, protein folding. Transcriptome analysis of
      L. lithophaga revealed a set of candidate genes putatively associated with
      chemical boring. The selected set of genes will be studied further to verify
      their expression patterns and their possible involvement in the rate of chemical
      boring in L. lithophaga.

PMID- 29454292
TI  - The nursification of a bioscience unit and its impact on student satisfaction and
      learning in an undergraduate nursing degree.
AB  - Undergraduate nursing students traditionally find bioscience difficult, which can
      be compounded by an inability to relate bioscience theory to nursing practice.
      Subsequently, many registered nurses feel they lack knowledge in this area.
      Several studies have identified this problem and focused on the importance of
      linking bioscience theory in undergraduate nursing curricula to clinical
      practice. The aim of this study was to assess whether nursification (the active
      association of a subject with nursing theory and practice) of the bioscience
      content of a first year, first semester unit impacts on the students' learning
      experience. The study compared two student groups' perceptions of their learning
      experience; one group enrolled before the bioscience unit was linked to nursing
      practice (pre-nursification) and the other group enrolled after the content was
      linked to nursing practice (post-nursification). Retrospective, quantitative
      analysis of the mean scores of the student feedback surveys found no significant
      difference between the pre and post-nursification responses with respect to the
      students' overall satisfaction of the unit or their ability to achieve their
      learning objectives, however the students in the post-nursification group
      reported significantly higher mean scores with respect to their motivation and
      inspiration to learn, and to learn effectively. The findings in this study
      suggest that integration of nursing practice within a bioscience unit can improve
      the learning experience of undergraduate nursing students.

PMID- 29454293
TI  - Health professions faculty beliefs, confidence, use, and perceptions of
      organizational culture and readiness for EBP: A cross-sectional, descriptive
      survey.
AB  - BACKGROUND: Evidence-based practice (EBP) is an essential skill and ethical
      obligation for all practicing health professions clinicians because of its strong
      association with improved health outcomes. Emerging evidence suggests that
      faculty who prepare these clinicians lack proficiency to teach EBP. OBJECTIVES:
      The purpose of this study was to describe; 1) health profession faculty beliefs
      about and confidence in their ability to teach and implement EBP, 2) use of EBP
      for education, 3) organizational culture and readiness for EBP; and to determine
      whether relationships exist among these variables. DESIGN: This study used a
      cross-sectional, descriptive survey design. SETTING AND PARTICIPANTS: College of
      Nursing (CON) and College of Health Professions (CHP) faculty from a university
      located in the Northeast, United States. Faculty were defined as anyone teaching
      a course for the CON or CHP during the fall of 2016. METHODS: Faculty were
      invited to complete an electronic survey measuring EBP beliefs, EBP use, and EBP
      organizational culture and readiness. The survey was comprised of three tools
      developed specifically for health professions educators in 2010 by Fineout
      Overholt & Melnyk. RESULTS: Sixty-nine faculty returned usable surveys (25.5%
      response rate). Mean EBP beliefs score was 89.49 (SD = 10.94) indicating
      respondents had a firm belief in and confidence in their ability to implement and
      teach EBP. Mean EBP use was 32.02 (SD = 20.59) indicating that respondents taught
      and implemented EBP between 1 and 3 times in the last 8-weeks. Mean EBP culture
      and readiness score was 90.20 (SD = 15.23) indicating essential movement toward a
      sustainable culture of college-wide integration of EBP. Mean scores for
      beliefs/confidence were higher for full-time clinical faculty compared to other
      groups [F(2, 55) = 0.075, p = 0.928; etap2 = 0.003)]. Adjunct faculty reported
      higher EBP behaviors expected by health profession educators in the last 8-weeks
      compared to other groups [F(2, 55) = 0.251, p = 0.779; etap2. =0.009)]. Adjunct
      faculty had the highest mean scores on OCRSIEP-E followed by full-time clinical
      faculty. These group differences in OCRSIEP-E were statistically significant
      [F(2, 49) = 7.92, p = 0.001; etap2 = 0.244)]. OCRSIEP-E was significantly
      different between full-time tenure/tenure track faculty (M = 78.0, SD = 12.58)
      and full-time clinical faculty (M = 91.37, SD = 14.79, p = 0.027) and between
      full-time tenure/tenure track faculty and adjunct faculty (M = 97.19, SD = 12.39,
      p = 0.001). CONCLUSIONS: Faculty adoption of EBP as a foundational pillar of
      teaching is essential. Research is needed to define the scope of the problem
      internationally. Organizations need to set standards for faculty teaching in the
      health professions to be EBP proficient. Programs preparing faculty to teach in
      nursing and other health professions must include educator EBP competencies.

PMID- 29454294
TI  - Parents' and early adolescents' self-efficacy about anger regulation and early
      adolescents' internalizing and externalizing problems: A longitudinal study in
      three countries.
AB  - The present study examines whether early adolescents' self-efficacy beliefs about
      anger regulation mediate the relation between parents' self-efficacy beliefs
      about anger regulation and early adolescents' internalizing and externalizing
      problems. Participants were 534 early adolescents (T1: M age = 10.89, SD = .70;
      50% female), their mothers (n = 534), and their fathers (n = 431). Families were
      drawn from Colombia, Italy, and the USA. Follow-up data were obtained two (T2)
      and three (T3) years later. At T1 and T3, parents' self-efficacy beliefs were
      self-reported and internalizing and externalizing problems were assessed via
      mothers', fathers', and early adolescents' reports. At T2, early adolescents'
      self-efficacy beliefs were self-reported Within the overall sample, mothers with
      higher self-efficacy beliefs about anger regulation had children with similar
      beliefs. Early adolescents' low self-efficacy beliefs were associated with higher
      internalizing and externalizing problems.

PMID- 29454295
TI  - Synthetic and genetically encoded fluorescent neural activity indicators.
AB  - The ultimate goal of neuroscience is to relate the complex activity of cells and
      cell-networks to behavior and cognition. This requires tools and techniques to
      visualize neuronal activity. Fluorescence microscopy is an ideal tool to measure
      activity of cells in the brain due to the high sensitivity of the technique and
      the growing portfolio of optical hardware and fluorescent sensors. Here, we give
      a chemist's perspective on the recent progress of fluorescent activity indicators
      that enable the measurement of cellular events in the living brain. We discuss
      advances in both chemical and genetically encoded sensors and look forward to
      hybrid indicators, which incorporate synthetic organic dyes into genetically
      encoded protein constructs.

PMID- 29454296
TI  - Effect of multiple low-dose PGF2alpha injections on the mature corpus luteum in
      non-pregnant bitches.
AB  - This study investigated molecular regulation in the canine corpus luteums/corpora
      lutea (CL) following multiple low-dose prostaglandin F2 alpha (PGF2alpha)
      injections in non-pregnant bitches around 30-35 days after ovulation. The CL were
      obtained by ovariohysterectomy 1 h after the last PGF2alpha injection. The
      subjects were divided into the following groups: control (no PGF2alpha injection,
      n = 4), one PGF2alpha injection (injection at 0 h, 1PGF, n = 4), two PGF2alpha
      injection (injection at 0 and 8 h, 2PGF, n = 4), and three PGF2alpha injection
      (injection at 0, 8 and 24 h, 3PGF, n = 4). In the 1PGF group, the steady-state
      mRNA levels of an immediate early gene (NR4A1) and immune system-related genes
      (MCP-1 and IL-8) increased. NR4A1 was localized in luteal and endothelial cells.
      In contrast, MCP-1 was localized in the luteal tissue between the luteal and
      endothelial cells. LHCGR, CYP11A1, and StAR mRNA expression decreased after the
      second PGF2alpha injection. FASLG increased only after the third PGF2alpha
      injection. The mRNA levels of PTGFR, PGT, and PTGS2 decreased as the number of
      PGF2alpha injections increased. Immunohistochemistry showed a decrease in StAR
      protein density as the number of PGF2alpha injections increased. BAX and CASP3
      mRNA expression levels were similar among the groups. Serum progesterone (P4)
      levels decreased dramatically after the PGF2alpha injections but were still
      higher than the basal level at the end of the study. In conclusion, repeated low
      dose PGF2alpha injections could induce luteolytic mechanisms in the CL of non
      pregnant bitches. Furthermore, it can be concluded that, in non-pregnant bitches,
      some aspects of the molecular regulation of luteolysis in the CL are similar to
      some aspects of such regulation in other domestic animals.

PMID- 29454297
TI  - Intracytoplasmic sperm injection (ICSI) of in vitro matured oocytes with stored
      epididymal spermatozoa in camel (Camelus dromedarius): Effect of exogenous
      activation on in vitro embryo development.
AB  - Experiments were conducted to investigate the development of in vitro matured
      camel oocytes after their intra-cytoplasmic sperm injection (ICSI) with
      epididymal sperm collected from slaughtered male camels. Ovaries and testes were
      collected from a local slaughterhouse in normal saline solution (NSS) at 37 
      degrees C and on ice (0-1  degrees C), respectively. Cumulus-oocyte complexes
      (COCs) aspirated from the follicles were randomly distributed to 4-well culture
      plates (20-25 COCs/well) containing 500 MUL of maturation medium and cultured at
      38.5  degrees C in an atmosphere of 5% CO2 in air for about 30 h. Spermatozoa
      were collected from the cauda epididymites in syringes containing 2-3 mL of tris
      tes egg yolk extender. They were cooled down slowly and stored at refrigeration
      (4  degrees C) temperature. On the day of use, spermatozoa were prepared by the
      swim up technique before use in ICSI. The injected oocytes were either activated
      by ionomycin and roscovitine or put into the culture without any chemical
      activation. In Experiment 1, presumptive zygotes were fixed and stained with
      Hoechst 33342 for evaluation of fertilization after 18 h of culture, while, in
      Experiment 2, they were cultured in 500 MUL of the culture medium at 38.5 
      degrees C in an atmosphere of 5% CO2, 5% O2 and 90% N2 in air for 7 days to
      evaluate their development. The proportion of oocytes activated when ICSI was
      followed by chemical activation was significantly higher (P < 0.05) when compared
      with non-activated ones. In experiment 2, a higher number of oocytes cleaved (59
      vs. 35%) and developed to blastocysts (20 vs. 7%) in the group with post-ICSI
      activation when compared with the group without chemical activation,
      respectively. In conclusion, to the best of our knowledge, this is the first
      report where embryos were produced by ICSI in camels. Chemical activation of
      oocytes by ionomycin and roscovitine, post -ICSI, enhanced their cleavage and
      development to blastocyst stage.

PMID- 29454298
TI  - Is the biparietal diameter of fetuses in late gestation too variable to predict
      readiness for cesarean section in dogs?
AB  - Correct assessment of readiness for cesarean section is essential for timing
      elective cesarean section during late pregnancy in the bitch. In humans,
      biparietal diameter is sufficiently precise and accurate and used in a clinical
      setting daily. The objectives of this study were to determine whether fetal
      biparietal diameter in late gestation in the dog could be used to predict
      readiness for cesarean section by having reached a minimum cut-off value and to
      correlate the biparietal diameter to birth weight. The biparietal diameter of 208
      puppies in 34 litters from 31 English bulldog bitches and 660 puppies in 78
      litters from 70 Boerboel bitches were measured immediately after delivery by
      cesarean section, performed at full term, using digital calipers. At the same
      time the birth weight of the same 208 English bulldog puppies and 494 of the same
      Boerboel puppies in 59 litters from 54 bitches was measured by means of an
      electronic scale. With a cesarean section, all the puppies in a litter are
      delivered simultaneously and readiness for cesarean section must be determined
      for a litter. The minimum, median and maximum biparietal diameter varied from
      21.1 to 47.8, 32.9 to 50.0 and 34.2-58.2 mm, respectively, among English bulldog
      litters and from 18.4 to 48.7, 35.5 to 49.7 and 39.8-54.3 mm among Boerboel
      litters. This large variation suggests that biparietal diameter is too variable
      within and among litters to be useful as a means of determining readiness for
      cesarean section.

PMID- 29454299
TI  - Congenital forms of diabetes: the beta-cell and beyond.
AB  - The majority of patients diagnosed with diabetes less than 6 months of age, and
      many cases diagnosed between 6 and 12 months of age, have a gene mutation that
      causes permanent or transient hyperglycemia. Recent research advances have
      allowed for the discovery of new causes of congenital diabetes, including genes
      involved in pancreatic development (GATA4, NKX2-2, MNX1) and monogenic causes of
      autoimmune dysregulation (STAT3, LRBA). Ongoing follow-up of patients with KCNJ11
      and ABCC8 mutations has supported the safety and efficacy of sulfonylureas, as
      well as the use of insulin pumps and continuous glucose monitors in infants with
      insulin-requiring forms of monogenic diabetes. Future studies are needed to
      improve clinical care and outcomes for these patients and their families.

PMID- 29454300
TI  - Gold-copper bimetallic nanoparticles supported on nano P zeolite modified carbon
      paste electrode as an efficient electrocatalyst and sensitive sensor for
      determination of hydrazine.
AB  - In this report, a facile, efficient and low cost electrochemical sensor based on
      bimetallic Au-Cu nanoparticles supported on P nanozeolite modified carbon paste
      electrode (Au-Cu/NPZ/CPE) was constructed and its efficiency for determination of
      hydrazine in trace level was studied. For this purpose, agro waste material, stem
      sweep ash (SSA) was employed as the starting material (silica source) for the
      synthesis of nano P zeolite (NPZ). After characterization of the synthesized NPZ
      by analytical instruments (scanning electronic microscopy (SEM), transmission
      electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared
      (FT-IR) spectroscopy), construction of Au-Cu/NPZ/CPE was performed by three steps
      procedure involving preparation of nano P zeolite modified carbon paste electrode
      (NPZ/CPE), introducing Cu+2 ions into nano zeolite structure by ion exchange and
      electrochemical reduction of Cu+2 ions upon applying constant potential. This
      procedure is followed by partial replacement of Cu by Au due to galvanic
      replacement reaction (GRR). The electrochemical properties of hydrazine at the
      surface of Au-Cu/NPZ/CPE was evaluated using cyclic voltammetry (CV),
      amperometry, and chronoamperometry methods in 0.1 M phosphate buffer solution
      (PBS). It was found that the prepared sensor has higher electrocatalytic activity
      at a relatively lower potential compared to other modified electrodes including
      Au/NPZ/CPE, Cu/NPZ/CPE, Au-Cu/CPE and etc. Moreover, the proposed electrochemical
      sensor presented the favorable analytical properties for determination of
      hydrazine such as low detection limit (0.04 uM), rapid response time (3 s), wide
      linear range (0.01-150 mM), and high sensitivity (99.53 uA mM-1) that are related
      to the synergic effect of bimetallic of Au-Cu, porous structure and enough
      surface area of NPZ. In addition, capability of Au-Cu/NPZ/CPE sensor was
      successfully tested in real samples with good accuracy and precision.

PMID- 29454301
TI  - Heteroassembled gold nanoparticles with sandwich-immunoassay LSPR chip format for
      rapid and sensitive detection of hepatitis B virus surface antigen (HBsAg).
AB  - This study aimed to develop a more sensitive method for the detection of
      hepatitis B surface antigen (HBsAg) using heteroassembled gold nanoparticles
      (AuNPs). A single layered localized surface plasmon resonance (LSPR) chip format
      was developed with antigen-antibody reaction-based detection symmetry using
      AuNPs, which detected HBsAg at 10 pg/mL. To further improve the detection limit,
      a modified detection format was fabricated by fixing a secondary antibody (to
      form a heteroassembled sandwich format) to the AuNP monolayer, which enhanced the
      detection sensitivity by about 100 times. The developed heteroassembled AuNPs
      sandwich-immunoassay LSPR chip format was able to detect as little as 100 fg/mL
      of HBsAg within 10-15 min. In addition, the heteroassembled AuNPs sandwich
      immunoassay LSPR chip format did not show any non-specific binding to other
      tested antigens, including alpha fetoprotein (AFP), C-reactive protein (CRP), and
      prostate-specific antigen (PSA). These findings confirm that the proposed
      detection strategy of heteroassembled AuNPs sandwich-immunoassay LSPR chip format
      may provide a new platform for early diagnosis of various human diseases.

PMID- 29454303
TI  - SMFM 2018: Meeting highlights-Friday (Podcast).

PMID- 29454302
TI  - Aerobic exercise inhibits obesity-induced respiratory phenotype.
AB  - PURPOSE: Obesity results in decreased lung function and increased inflammation.
      Moderate aerobic exercise (AE) reduced lung inflammation and remodeling in a
      variety of respiratory disease models. Therefore, this study investigated whether
      AE can attenuate a diet-induced obesity respiratory phenotype; including airway
      hyper-responsiveness (AHR), remodeling and inflammation. METHODS: Sixty C57Bl/6
      male mice were distributed into four groups: control lean (CL), exercise lean
      (EL), obese (O) and obese exercise (OE) groups (2 sets of 7 and 8 mice per group;
      n = 15). A classical model of diet-induced obesity (DIO) over 12 weeks was used.
      AE was performed 60 min/day, 5 days/week for 5 weeks. Airway hyperresponsiveness
      (AHR), lung inflammation and remodeling, adipokines and cytokines in
      bronchoalveolar lavage (BAL) was determined. RESULTS: A high fat diet over 18
      weeks significantly increased body weight (p < .0001). Five weeks of AE
      significantly reduced both AHR and pulmonary inflammation. AHR in obese mice that
      exercised was reduced at the basal level (p < .05), vehicle (PBS) (p < .05), 6.25
      MCh mg/mL (p < .05), 12.5 MCh mg/mL (p < .01), 25 MCh mg/mL (p < .01) and 50 MCh
      mg/mL (p < .05). Collagen (p < .001) and elastic (p < .001) fiber deposition in
      airway wall and also smooth muscle thickness (p < .001) were reduced. The number
      of neutrophils (p < .001), macrophages (p < .001) and lymphocytes (p < .01) were
      reduced in the peribronchial space as well as in the BAL: lymphocytes (p < .01),
      macrophages (p < .01), neutrophils (p < .001). AE reduced obesity markers leptin
      (p < .001), IGF-1 (p < .01) and VEGF (p < .001), while increased adiponectin (p <
      .01) in BAL. AE also reduced pro-inflammatory cytokines in the BAL: IL-1beta (p <
      .001), IL-12p40 (p < .001), IL-13 (p < .01), IL-17 (p < .001, IL-23 (p < .05) and
      TNF-alpha (p < .05), and increased anti-inflammatory cytokine IL-10 (p < .05).
      CONCLUSIONS: Aerobic exercise reduces high fat diet-induced obese lung phenotype
      (AHR, pulmonary remodeling and inflammation), involving anti-inflammatory
      cytokine IL-10 and adiponectin.

PMID- 29454304
TI  - First and second eye cataract surgery and driver self-regulation among older
      drivers with bilateral cataract: a prospective cohort study.
AB  - BACKGROUND: Driving a car is the most common form of transport among the older
      population. Common medical conditions such as cataract, increase with age and
      impact on the ability to drive. To compensate for visual decline, some cataract
      patients may self-regulate their driving while waiting for cataract surgery.
      However, little is known about the self-regulation practices of older drivers
      throughout the cataract surgery process. The aim of this study is to assess the
      impact of first and second eye cataract surgery on driver self-regulation
      practices, and to determine which objective measures of vision are associated
      with driver self-regulation. METHODS: Fifty-five older drivers with bilateral
      cataract aged 55+ years were assessed using the self-reported Driving Habits
      Questionnaire, the Mini-Mental State Examination and three objective visual
      measures in the month before cataract surgery, at least one to three months after
      first eye cataract surgery and at least one month after second eye cataract
      surgery. Participants' natural driving behaviour in four driving situations was
      also examined for one week using an in-vehicle monitoring device. Two separate
      Generalised Estimating Equation logistic models were undertaken to assess the
      impact of first and second eye cataract surgery on driver-self-regulation status
      and which changes in visual measures were associated with driver self-regulation
      status. RESULTS: The odds of being a self-regulator in at least one driving
      situation significantly decreased by 70% after first eye cataract surgery (OR:
      0.3, 95% CI: 0.1-0.7) and by 90% after second eye surgery (OR: 0.1, 95% CI: 0.1
      0.4), compared to before first eye surgery. Improvement in contrast sensitivity
      after cataract surgery was significantly associated with decreased odds of self
      regulation (OR: 0.02, 95% CI: 0.01-0.4). CONCLUSIONS: The findings provide a
      strong rationale for providing timely first and second eye cataract surgery for
      older drivers with bilateral cataract, in order to improve their mobility and
      independence.

PMID- 29454305
TI  - Psychotropic and anti-dementia treatment in elderly persons with clinical signs
      of dementia with Lewy bodies: a cross-sectional study in 40 nursing homes in
      Sweden.
AB  - BACKGROUND: Elderly persons with a dementia diagnosis often suffer from different
      neuropsychiatric symptoms (NPS) such as delusions, hallucinations, depression,
      anxiety, irritability and agitation. Currently, the medical treatment for NPS
      consists mostly of psychotropic medication such as hypnotics/sedatives,
      anxiolytics and antipsychotics. In elderly persons with dementia, usage of
      antipsychotics is less appropriate because of the risk of side effects such as
      parkinsonism, rapid cognitive decline, cerebrovascular events and finally
      mortality. Furthermore, elderly persons with dementia with Lewy bodies (DLB) are
      often hypersensitive to antipsychotics with numerous serious adverse events such
      as somnolence, sedation, extra-pyramidal symptoms, delirium and increased
      mortality. The aim of this study was to investigate the usage of psychotropics
      with a focus on antipsychotics and anti-dementia medication (according to the
      Anatomical Therapeutic Chemical Classification System) in elderly persons with
      clinical signs of DLB living in dementia nursing homes (NHs) in Sweden. METHODS:
      Between 2012 and 2013, we applied a specially designed questionnaire that covered
      the clinical DLB features according to the consensus criteria of DLB. We also
      collected computerized medical lists from the Swedish National Medication
      Dispensing System from the same period. All dementia NHs (n = 40) in Malmo, the
      third largest city in Sweden, were covered. Of 650 eligible residents, 610 (94%)
      were included with 576 medical lists. The mean age was 86 years and 76% were
      women. RESULTS: Treatment with antipsychotics was seen in 22% of residents,
      hypnotics/sedatives in 41%, antidepressants in 50% and anxiolytics in 58%. We
      also found an increasing usage of antipsychotics from 25% to 43% in residents
      with the increasing number of DLB features. Anti-dementia medications were found
      in 45% of the elderly with a dementia diagnosis. However, residents with two or
      more DLB features had less anti-dementia medication (37%) than the rest of the
      dementia-diagnosed NH residents (62-69%). CONCLUSIONS: Residents with 2-4 DLB
      clinical features in Swedish NHs receive an unfavourable medical treatment with
      high antipsychotic usage and insufficient anti-dementia medication. These
      findings show the importance of identifying elderly persons with DLB features
      more effectively and improving the collaboration with nursing care to provide
      better medical prescription.

PMID- 29454306
TI  - RECORD-4 multicenter phase 2 trial of second-line everolimus in patients with
      metastatic renal cell carcinoma: Asian versus non-Asian population subanalysis.
AB  - BACKGROUND: RECORD-4 assessed everolimus in patients with metastatic renal cell
      carcinoma (mRCC) who progressed after 1 prior anti-vascular endothelial growth
      factor (VEGF) or cytokine and reinforced the clinical benefit of second-line
      everolimus. Because of the high percentage of patients from China enrolled in
      RECORD-4 (41%) and some reported differences in responses to certain targeted
      agents between Chinese and Western patients, this subanalysis evaluated outcomes
      in Asian versus non-Asian patients. METHODS: RECORD-4 enrolled patients with
      clear cell mRCC into 3 cohorts based on prior first-line therapy: sunitinib,
      other anti-VEGF (sorafenib, bevacizumab, pazopanib, other), or cytokines.
      Patients received everolimus 10 mg/d until progression of disease (RECIST, v1.0)
      or intolerance. Primary end point was progression-free survival per investigator
      review. Data cutoff was Sept 1, 2014. RESULTS: Among Asian (n = 55) versus non
      Asian (n = 79) patients, 98% versus 84% had good/intermediate MSKCC prognosis;
      73% versus 65% were men, and 85% versus 73% were < 65 years of age. All (100%)
      Asian patients were of Chinese ethnicity. Median duration of exposure was 5.5 mo
      for Asian and 6.0 mo for non-Asian patients. Among Asian versus non-Asian
      patients, median progression-free survival (months) was 7.4 versus 7.8 overall,
      7.4 versus 4.0 with prior sunitinib, and 5.7 versus 9.2 with prior other anti
      VEGFs. Clinical benefit rate was similar between populations: 74.5% (95% CI 61.0
      85.3) for Asian patients and 74.7% (95% CI 63.6-83.8) for non-Asian patients.
      Most patients achieved stable disease as best overall response (Asian, 63.6%; non
      Asian, 69.6%). Overall rate of grade 3/4 adverse events appeared similar for
      Asian (58%) and non-Asian patients (54%). CONCLUSIONS: This RECORD-4 subanalysis
      demonstrated comparable efficacy and adverse event profiles of second-line
      everolimus in Asian and non-Asian patients. Efficacy and safety outcomes by prior
      therapy should be interpreted with caution because of small patient numbers in
      some subpopulations. TRIAL REGISTRATION: Everolimus as Second-line Therapy in
      Metastatic Renal Cell. Carcinoma (RECORD-4); ClinicalTrials.gov identifier:
      NCT01491672 . Registration date: December 14, 2011.

PMID- 29454307
TI  - Association between residual teeth number in later life and incidence of
      dementia: A systematic review and meta-analysis.
AB  - BACKGROUND: It has been suggested that tooth loss in later life might increase
      dementia incidence. The objective of this analysis is to systematically review
      the current evidence on the relationship between the number of remaining teeth
      and dementia occurrence in later life. METHODS: A search of multiple databases of
      scientific literature was conducted with relevant parameters for articles
      published up to March 25th, 2017. Multiple cohort studies that reported the
      incidence of dementia and residual teeth in later life were found with
      observation periods ranging from 2.4 to 32 years. Random-effects pooled odds
      ratios (OR) and 95% confidence intervals (CI) were estimated to examine whether
      high residual tooth number in later life was associated with a decreased risk of
      dementia. Heterogeneity was measured by I2. The Grading of Recommendations
      Assessment, Development, and Evaluation (GRADE) system was used to assess the
      overall quality of evidence. RESULTS: The literature search initially yielded 419
      articles and 11 studies (aged 52 to 75 at study enrollment, n = 28,894) were
      finally included for analysis. Compared to the low residual teeth number group,
      the high residual teeth number group was associated with a decreased risk of
      dementia by approximately 50% (pooled OR = 0.483; 95% CI 0.315 to 0.740; p <
      0.001; I2 = 92.421%). The overall quality of evidence, however, was rated as very
      low. CONCLUSION: Despite limited scientific strength, the current meta-analysis
      reported that a higher number of residual teeth was associated with having a
      lower risk of dementia occurrence in later life.

PMID- 29454308
TI  - The unique evolutionary pattern of the Hydroxyproline-rich glycoproteins
      superfamily in Chinese white pear (Pyrus bretschneideri).
AB  - BACKGROUND: The hydroxyproline-rich glycoprotein (HRGP) superfamily, comprising
      three families (arabinogalactan-proteins, AGPs; extensins, EXTs; proline-rich
      proteins, PRPs), is a class of proline-rich proteins that exhibit high diversity
      and are involved in many aspects of plant biology. RESULTS: In this study, 838
      HRGPs were identified from Chinese white pear (Pyrus bretschneideri) by searching
      for biased amino acid composition and conserved motifs. 405 HRGPs were derived
      from whole genome duplication (WGD) events which is suggested to be the major
      force of driving HRGPs expansion and the recent WGD event shared by apple and
      pear generated most duplicated HRGPs in pear. This duplication event drived the
      structural variation of the HRGPs encoding hydroxyproline (Hyp)-rich motifs. The
      rate of HRGPs evolution mainly impacted the Hyp-rich motifs even in chimeric
      HRGPs. During the evolution of 53 PRPs that are also typified by 7-deoxyloganetin
      glucosyltransferase-like genes, the duplication from PRP to non-PRP was
      indirectly modified by positive selection. These results suggested that the rate
      of HRGP evolution mainly influenced the Hyp-rich motifs even in chimeric HRGPs.
      The expression divergence of HRGPs was higher than that of other commonly
      duplicated genes. In pear pistil, 601 HRGPs exhibited expression, while in pear
      pollen, 285 HRGPs were expressed. The qPCR results revealed that Pbr036330.1 and
      Pbr010506.1 showed different expression profile in self-incompatibility of pear
      pistil. CONCLUSIONS: The researches indicated that WGD events was the main
      duplication type during the evolution of HRGPs, and the highly variable Hyp
      motifs might be accountable for the expansion, evolution and expression
      divergence of HRGPs and that this divergence may be responsible for the gain of
      new functions in plants.

PMID- 29454309
TI  - Perceptions about screening for prostate cancer using genetic lifetime risk
      assessment: a qualitative study.
AB  - BACKGROUND: Most health authorities do not recommend screening for prostate
      cancer with PSA tests in asymptomatic patients who are not at increased risk.
      However, opportunistic screening for prostate cancer is still wanted by many
      patients and it is widely used in primary care clinics, with potential for
      overdiagnosis and overtreatment. Better tools for risk assessment have been
      called for, to better target such opportunistic screening. Our aim was to explore
      perceptions about prostate cancer risk and subsequent opportunistic screening
      among patients who were not at increased risk of prostate cancer after a first
      PSA test plus a genetic lifetime risk assessment. METHODS: We undertook semi
      structured patient interviews with recording and verbatim transcription of
      interviews. Data were analysed thematically. RESULTS: Three themes were
      identified: uncertainty of the nature of prostate cancer; perceived benefits of
      testing; and conflicting public health recommendations. Prostate cancer was
      spoken of as an inescapable risk in older age. The aphorism "you die with it, not
      from it" was prominent in the interviews but patients focused on the benefits of
      testing now rather than the future risks associated with treatment relating to
      potential overdiagnosis. Many expressed frustration with perceived mixed messages
      about early detection of cancer, in which on one side men feel that they are
      encouraged to seek medical testing to act responsibly regarding the most common
      cancer disease in men, and on the other side they are asked to refrain from
      opportunistic testing for prostate cancer. Taken together, personal risks of
      prostate cancer were perceived as high in spite of a normal PSA test and a
      genetic lifetime risk assessment showing no increased risk. CONCLUSION: Patients
      saw prostate cancer risk as high and increasing with age. They focused on the
      perceived benefit of early detection using PSA testing. It was also commonly
      acknowledged that most cases are indolent causing no symptoms and not shortening
      life expectancy. There was a frustration with mixed messages about the benefit of
      early detection and risk of overdiagnosis. These men's genetic lifetime risk
      assessment showing no increased risk did not appear to influence current
      intentions to get PSA testing in the future.

PMID- 29454310
TI  - In vitro and in silico validation of CA3 and FHL1 downregulation in oral cancer.
AB  - BACKGROUND: Aberrant methylation is a frequent event in oral cancer. METHODS: In
      order to better characterize these alterations, a search for genes downregulated
      by aberrant methylation in oral squamous cell carcinoma (OSCC) was conducted
      through the mining of ORESTES dataset. Findings were further validated in OSCC
      cell lines and patients' samples and confirmed using TCGA data. Differentially
      expressed genes were identified in ORESTES libraries and validated in vitro using
      RT-PCR in HNSCC cell-lines and OSCC tumor samples. Further confirmation of these
      results was performed using mRNA expression and methylation data from The Cancer
      Genome Atlas (TCGA) data. RESULTS: From the set of genes selected for validation,
      CA3 and FHL1 were downregulated in 60% (12/20) and 75% (15/20) of OSCC samples,
      respectively, and in HNSCC cell lines. The treatment of cell lines JHU-13 and
      FaDu with the demethylating agent 5'-aza-dC was efficient in restoring CA3 and
      FHL1 expression. TCGA expression and methylation data on OSCC confirms the
      downregulation of these genes in OSCC samples and also suggests that expression
      of CA3 and FHL1 is probably regulated by methylation. The downregulation of CA3
      and FHL1 observed in silico was validated in HNSCC cell lines and OSCC samples,
      showing the feasibility of integrating different datasets to select
      differentially expressed genes in silico. CONCLUSIONS: These results showed that
      the downregulation of CA3 and FHL1 data observed in the ORESTES libraries was
      validated in HNSCC cell lines and OSCC samples and in a large cohort of samples
      from the TCGA database. Moreover, it suggests that expression of CA3 and FHL1
      could probably be regulated by methylation having an important role the oral
      carcinogenesis.

PMID- 29454311
TI  - Radiotherapy related skin toxicity (RAREST-01): Mepitel(r) film versus standard
      care in patients with locally advanced head-and-neck cancer.
AB  - BACKGROUND: The aim of the present trial is to investigate a new option of skin
      protection in order to reduce the rate of grade >= 2 skin toxicity in patients
      receiving radiotherapy alone or radiochemotherapy for locally advanced squamous
      cell carcinoma of the head-and-neck (SCCHN). METHODS / DESIGN: This is a
      randomized, active-controlled, parallel-group multi-center trial that compares
      the following treatments of radiation dermatitis in patients with head-and-neck
      cancer: Mepitel(r) Film (Arm A) vs. standard care (Arm B). The primary aim of
      this trial is to investigate the rate of patients experiencing grade >= 2
      radiation dermatitis (according to Common Toxicity Criteria for Adverse Events
      (CTCAE) Version 4.03) until 50 Gy of radiotherapy. Evaluation until 50 Gy of
      radiotherapy has been selected as the primary endpoint, since up to 50 Gy, the
      irradiated volume includes the primary tumor and the bilateral cervical and
      supraclavicular lymph nodes, and, therefore, is similar in all patients. After 50
      Gy, irradiated volumes are very individual, depending on location and size of the
      primary tumor, involvement of lymph nodes, and the treatment approach (definitive
      vs. adjuvant). In addition, the following endpoints will be evaluated: Time to
      grade 2 radiation dermatitis until 50 Gy of radiotherapy, rate of patients
      experiencing grade >= 2 radiation dermatitis during radio(chemo)therapy, rate of
      patients experiencing grade >= 3 skin toxicity during radio(chemo)therapy,
      adverse events, quality of life, and dermatitis-related pain. Administration of
      Mepitel(r) Film will be considered to be clinically relevant, if the rate of
      grade >= 2 radiation dermatitis can be reduced from 85% to 65%. DISCUSSION: If
      administration of Mepitel(r) Film instead of standard care will be able to
      significantly reduce the rate of grade >= 2 radiation dermatitis, it could become
      the new standard of skin care in patients irradiated for SCCHN. TRIAL
      REGISTRATION: clinicaltrials.gov NCT03047174 . Registered on 26th of January,
      2017. First patient included on 9th of May, 2017.

PMID- 29454312
TI  - Effects of a wide range of dietary forage-to-concentrate ratios on nutrient
      utilization and hepatic transcriptional profiles in limit-fed Holstein heifers.
AB  - BACKGROUND: Improving the efficiency of animal production is a relentless pursuit
      of ruminant producers. Energy utilization and partition can be affected by
      dietary composition and nutrient availability. Furthermore, the liver is the
      central metabolic intersection in cattle. However, the specific metabolic changes
      in the liver under conditions of limit-feeding remain unclear and require further
      study. The present study aimed to elucidate the effects of a wide range of
      dietary forage:concentrate ratios (F:C) on energy utilization, and identify
      potential changes in molecular metabolism by analyzing hepatic transcriptional
      profiles. Twenty-four half-sib Holstein heifers were fed four F:C diets (20:80,
      40:60, 60:40, and 80:20 on a dry matter basis), with similar intake levels of
      metabolizable energy (ME) and crude protein. Liver biopsy samples were obtained
      and RNA sequencing was conducted to identify the hepatic transcriptomic changes.
      Moreover, the ruminal fermentation profiles, growth characteristics, and levels
      of metabolites in the liver and plasma of the heifers were monitored. RESULTS:
      The proportion of acetate showed a linear increase (P < 0.01) with increasing
      dietary forage levels, whereas the proportion of propionate showed a linear
      decline (P <= 0.01). Lower levels of average daily gain and feed efficiency (P <
      0.01) were observed in heifers fed high levels of forage, with a significant
      linear response. Using the Short Time-series Expression Miner software package,
      the expression trends of significant differentially expressed genes (DEGs) were
      generally divided into 20 clusters, according to their dynamic expression
      patterns. Functional classification analysis showed that lipid metabolism
      (particularly cholesterol and steroid metabolism which were in line with the
      cholesterol content in the liver and plasma) was significantly increased with
      increasing dietary forage levels and slightly reduced by the 80% forage diet.
      Nine DEGs were enriched in the related pathways, namely HMGCS1, HMGCR, MSMO1,
      MVK, MVD, IDI1, FDPS, LSS, and DHCR7. CONCLUSIONS: The ruminal fermentation and
      feed efficiency results suggest that different mechanisms of energy utilization
      might occur in heifers fed different F:C diets with similar levels of ME intake.
      Increased cholesterol synthesis from acetate might be responsible for the reduced
      efficiency of energy utilization in heifers fed high-forage diets.

PMID- 29454313
TI  - StructRNAfinder: an automated pipeline and web server for RNA families
      prediction.
AB  - BACKGROUND: The function of many noncoding RNAs (ncRNAs) depend upon their
      secondary structures. Over the last decades, several methodologies have been
      developed to predict such structures or to use them to functionally annotate RNAs
      into RNA families. However, to fully perform this analysis, researchers should
      utilize multiple tools, which require the constant parsing and processing of
      several intermediate files. This makes the large-scale prediction and annotation
      of RNAs a daunting task even to researchers with good computational or
      bioinformatics skills. RESULTS: We present an automated pipeline named
      StructRNAfinder that predicts and annotates RNA families in transcript or genome
      sequences. This single tool not only displays the sequence/structural consensus
      alignments for each RNA family, according to Rfam database but also provides a
      taxonomic overview for each assigned functional RNA. Moreover, we implemented a
      user-friendly web service that allows researchers to upload their own nucleotide
      sequences in order to perform the whole analysis. Finally, we provided a stand
      alone version of StructRNAfinder to be used in large-scale projects. The tool was
      developed under GNU General Public License (GPLv3) and is freely available at
      http://structrnafinder.integrativebioinformatics.me . CONCLUSIONS: The main
      advantage of StructRNAfinder relies on the large-scale processing and integrating
      the data obtained by each tool and database employed along the workflow, of which
      several files are generated and displayed in user-friendly reports, useful for
      downstream analyses and data exploration.

PMID- 29454314
TI  - A prospective study to investigate the role of serial serum mesothelin in
      monitoring mesothelioma.
AB  - BACKGROUND: Radiological monitoring of malignant pleural mesothelioma (MPM) using
      modified RECIST criteria is limited by low sensitivity and inter-observer
      variability. Serial serum mesothelin measurement has shown utility in the
      assessment of treatment response during chemotherapy but has never been assessed
      in the longer term follow up of patients. METHODS: This is a single centre study
      of consecutive patients diagnosed with MPM who received chemotherapy or best
      supportive care (BSC). Serum mesothelin measurements with paired 6 monthly CT
      scans were performed following the completion of chemotherapy, or from baseline
      in the BSC group. Changes in mesothelin were correlated with radiological
      progression and overall survival. RESULTS: Forty-one patients with MPM were
      recruited and followed up for a minimum of 12 months (range 12-21 months). The
      majority of patients (n = 23) received chemotherapy with pemetrexed and
      cisplatin. Across the cohort a 10% rise in serum mesothelin could predict
      radiological progression with a sensitivity of 96% (IQR; 79-100) and specificity
      of 74% (IQR; 50-91). Sensitivity fell to 80% in sarcomatoid only disease.
      Patients with a rising mesothelin at 6 months had significantly worse overall
      survival (175 days) compared to stable/falling levels (448 days) (p = 0.003).
      CONCLUSIONS: This is the first study to assess serum mesothelin's ability to
      detect progression of MPM following chemotherapy or during BSC. A 10% rise in
      serum mesothelin level showed excellent sensitivity at predicting progressive
      disease. Mesothelin measurement has several advantages over serial CT imaging
      including reducing hospital visits and cost.

PMID- 29454315
TI  - Prevalence and correlates of positive mental health in Chinese adolescents.
AB  - BACKGROUND: Studies investigating the prevalence of positive mental health and
      its correlates are still scarce compared to the studies on mental disorders,
      although there is growing interest of assessing positive mental health in
      adolescents. So far, no other study examining the prevalence and determinants of
      positive mental health in Chinese adolescents has been found. The purpose of this
      study was to assess the prevalence and correlates of positive mental health in
      Chinese adolescents. METHODS: This cross-sectional study used a questionnaire
      including Mental Health Continuum-Short Form (MHC-SF) and items regarding
      multiple aspects of adolescent life. The sample involved a total of 5399 students
      from grade 8 and 10 in Weifang, China. Multivariate Logistic regression analyses
      were performed to evaluate the associations between potential indicators
      regarding socio-economic situations, life style, social support and school life
      and positive mental health and calculate odds ratios and 95% confidence
      intervals. RESULTS: More than half (57.4%) of the participants were diagnosed as
      flourishing. The correlated factors of positive mental health in regression
      models included gender, perceived family economy, the occurrence of sibling(s),
      satisfaction of self-appearance, physical activity, sleep quality, stress, social
      trust, desire to learn, support from teachers and parents as well as whether
      being bullied at school (OR ranging from 1.23 to 2.75). The Hosmer-Lemeshow p
      value for the final regression model (0.45) indicated adequate model fit.
      CONCLUSION: This study gives the first overview on prevalence and correlates of
      positive mental health in Chinese adolescents. The prevalence of positive mental
      health in Chinese adolescents is higher than reported in most of the previous
      studies also using MHC-SF. Our findings suggest that adolescents with
      advantageous socio-economic situations, life style, social support and school
      life are experiencing better positive mental health than others.

PMID- 29454316
TI  - The theoretical and empirical basis of a BioPsychoSocial (BPS) risk screener for
      detection of older people's health related needs, planning of community programs,
      and targeted care interventions.
AB  - BACKGROUND: This study introduces the conceptual basis and operational measure,
      of BioPyschoSocial (BPS) health and related risk to better understand how well
      older people are managing and to screen for risk status. The BPS Risk Screener is
      constructed to detect vulnerability at older ages, and seeks to measure dynamic
      processes that place equal emphasis on Psycho-emotional and Socio-interpersonal
      risks, as Bio-functional ones. We validate the proposed measure and describe its
      application to programming. METHODS: We undertook a quantitative cross-sectional,
      psychometric study with n = 1325 older Singaporeans, aged 60 and over. We adapted
      the EASYCare 2010 and Lubben Social Network Scale questionnaires to help
      determine the BPS domains using factor analysis from which we derive the BPS Risk
      Screener items. We then confirm its structure, and test the scoring system. The
      score is initially validated against self-reported general health then modelled
      against: number of falls; cognitive impairment; longstanding diseases; and
      further tested against service utilization (linked administrative data). RESULTS:
      Three B, P and S clusters are defined and identified and a BPS managing score
      ('doing' well, or 'some', 'many', and 'overwhelming problems') calculated such
      that the risk of problematic additive BPS effects, what we term health 'loads',
      are accounted for. Thirty-five items (factor loadings over 0.5) clustered into
      three distinct B, P, S domains and were found to be independently associated with
      self-reported health: B: 1.99 (1.64 to 2.41), P: 1.59 (1.28 to 1.98), S: 1.33
      (1.10 to 1.60). The fit improved when combined into the managing score 2.33 (1.92
      to 2.83, < 0.01). The score was associated with mounting risk for all outcomes.
      CONCLUSIONS: BPS domain structures, and the novel scoring system capturing
      dynamic BPS additive effects, which can combine to engender vulnerability, are
      validated through this analysis. The resulting tool helps render clients' risk
      status and related intervention needs transparent. Given its explicit and
      empirically supported attention to P and S risks, which have the potential to be
      more malleable than B ones, especially in the older old, this tool is designed to
      be change sensitive.

PMID- 29454317
TI  - Oxidative damage and response to Bacillus Calmette-Guerin in bladder cancer cells
      expressing sialyltransferase ST3GAL1.
AB  - BACKGROUND: Treatment with Bacillus Calmette-Guerin (BCG) is the gold standard
      adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it
      fails in one third of the patients. NMIBC expresses two tumor-associated O-linked
      carbohydrates: the disaccharide (Galbeta1,3GalNAc) Thomsen-Friedenreich (T)
      antigen, and its sialylated counterpart (Siaalpha2,3Galbeta1,3GalNAc) sialyl-T
      (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are
      unknown. METHODS: The human bladder cancer (BC) cell line HT1376 strongly
      expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or
      with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express,
      respectively, either the sT or the T antigens. Cells were in vitro challenged
      with BCG. Whole gene expression was studied by microarray technology, cytokine
      secretion was measured by multiplex immune-beads assay. Human macrophages derived
      from blood monocytes were challenged with the secretome of BCG-challenged BC
      cells. RESULTS: The secretome from BCG-challenged HT1376sT cells induced a
      stronger macrophage secretion of IL-6, IL-1beta, TNFalpha and IL-10 than that of
      HT1376T cells. Transcriptomic analysis revealed that ST3GAL1 overexpression and
      T/sT replacement modulated hundreds of genes. Several genes preserving genomic
      stability were down-regulated in HT1376sT cells which, as a consequence,
      displayed increased sensitivity to oxidative damage. After BCG challenge, the
      transcriptome of HT1376sT cells showed higher susceptibility to BCG modulation
      than that of HT1376T cells. CONCLUSIONS: High ST3GAL1 expression and T/sT
      replacement in BCG challenged-BC cancer cells induce a stronger macrophage
      response and alter the gene expression towards genomic instability, indicating a
      potential impact on BC biology and patient's response to BCG.

PMID- 29454318
TI  - Points-based physical activity: a novel approach to facilitate changes in body
      composition in inactive women with overweight and obesity.
AB  - BACKGROUND: Physical activity (PA) interventions for the promotion of weight
      management may benefit from increased choice and flexibility to overcome commonly
      perceived barriers to PA. The aim of this study was to investigate the effects of
      a novel "points-based" approach to PA on body composition in inactive women, who
      are overweight or obese. METHODS: Seventy-six overweight or obese, inactive women
      were randomly allocated to one of three conditions: 'Points-based' PA (PBPA; 30
      "PA points"*week- 1), Structured exercise (StructEx; 150 min moderate-intensity
      exercise*week- 1) or control (CONT; continue habitual inactive lifestyle) for a
      24-week intervention. PA points for activities were adapted from MET values, and
      30 points was equivalent to 150 min of brisk walking. Measures of body
      composition (dual-energy x-ray absorptiometry) and anthropometry were obtained at
      weeks 0, 4, 12 and 24. Self-report activities were recorded weekly, with
      objective measures of PA (tri-axial accelerometry) and self-report measures of
      food intake obtained at weeks 0 and 24. RESULTS: Fifty-eight women completed the
      study and provided data for primary outcomes. Of these, n = 41 and n = 19
      provided data for food intake and objectively assessed PA. Mixed-design ANOVAs
      demonstrated that those in PBPA achieved a significant weight-loss at 24 weeks of
      - 3.3 +/- 5.9 kg (- 3.4 +/- 7.1%, p = 0.004). Waist circumference was reduced in
      PBPA at 24 weeks (- 2.8 +/- 4.6 cm), compared with CONT (+ 2.1 +/- 6.6 cm, p =
      0.024). There was a trend for greater reductions in fat mass for those in PBPA
      vs. CONT (- 2.3 +/- 4.6 kg vs. + 0.1 +/- 2.0 kg, p = 0.075). Android fat was
      reduced in PBPA at both 12 weeks (- 6.1 +/- 12.6%, p = 0.005) and 24 weeks (-
      10.1 +/- 18.4%, p = 0.005), while there was a trend for greater reductions in
      visceral adipose tissue in PBPA (- 5.8 +/- 26.0%) vs. CONT at 24 weeks (+ 7.8 +/-
      18.3%, p = 0.053). Body composition, body weight and waist circumference were
      unchanged in StructEx. There were trends for increases in light-activity and
      reductions in sedentary time in PBPA. There was a trend for a reduction in daily
      energy intake of - 445 +/- 564 kcal (p = 0.074), and a significant reduction in
      daily fat intake (p = 0.042) in PBPA. CONCLUSION: A "points-based" approach to
      physical activity appears to be an effective strategy for inducing modest
      reductions in body weight and body fat in inactive women with overweight and
      obesity. TRIAL REGISTRATION: NCT02020239 . Registered 12th December 2013.

PMID- 29454319
TI  - Treatment of upper tract urothelial carcinoma with ureteroscopy and thulium
      laser: a retrospective single center study.
AB  - BACKGROUND: Treatment with the combination of ureteroscopy and thulium laser
      ablation may provide an alternative to radical nephroureterectomy (RNU) for
      patients with upper tract urothelial carcinoma (UTUC). The purpose of this study
      was to investigate the efficacy and safety of this technique. METHODS: We
      performed a retrospective review of the data for patients who were treated
      surgically for upper tract urothelial carcinoma in a single center. It included
      32 patients treated by endoscopic thulium laser resection and 107 patients
      treated by radical nephroureterectomy (RNU). We compared the data of patient sex,
      age at diagnosis, location of carcinoma, length of hospitalization, tumor site,
      size, grade, recurrence, preoperative creatinine and postoperative creatinine in
      two groups. Patients were examined by ureteroscopy every 3 months during the
      first year after surgery, then every 6 months each year. RESULTS: All 32 patients
      were treated successfully, among which 6 were operated by a flexible
      ureteroscope. The average tumor size was 13 +/- 7 mm in diameter. The tumor was
      rated as low grade in 27 patients and high grade in 5 patients. Ureteral
      stricture developed in 4 patients 3 months later after surgery, but the stricture
      was succesfully treated through endoscopic dilation. Seven patients had tumor
      recurrence, 3 of which underwent nephroureterectomy during the follow-up.
      Postoperative creatinine levels (umol/L) were respectively 89 +/- 7.5 in laser
      group and 123 +/- 15.4 in RNU group (p < 0.01). Length of hospitalization was
      respectively 3.6 +/- 1.9 and 8.6 +/- 2.4 days (p < 0.01). Local or bladder
      recurrence rate of thulium laser group and RNU group was respectively 21.9 and
      13.1% (p < 0.01). CONCLUSIONS: Thulium laser group is associated with a less loss
      of renal function, a shorter length of hospitalization, but a higher rate of
      tumor recurrence. Thulium laser therapy combined with ureteroscopic treatment can
      be considered as an acceptable treatment for selected cases of UTUC. Lifetime
      intensive surveillance is necessary.

PMID- 29454320
TI  - Obesity and caries in four-to-six year old English children: a cross-sectional
      study.
AB  - BACKGROUND: Obesity and caries are common conditions in childhood and can have
      significant implications on children's wellbeing. Evidence into their association
      remains conflicting. Furthermore, studies examining the ssociation between
      obesity and caries commonly focus on individual-level determinants. The present
      study aimed to examine the association between obesity and caries in young
      English children and to determine the impact of deprivation and area-level
      characteristics on the distribution of the two conditions. METHODS: This was a
      cross-sectional study among children in Plymouth city aged four-to-six years.
      Anthropometric measurements included weight and height (converted to Body Mass
      Index centiles and z-scores), and waist circumference. Caries was assessed by
      using the sum of the number of teeth that were decayed, missing or filled. A
      questionnaire was used to obtain information on children's demographic
      characteristics, oral hygiene, and dietary habits. The impact of deprivation on
      anthropometric variables and caries was determined using Linear and Poisson
      regression models, respectively. Multiple logistic regression was used to assess
      the association between different anthropometric measures and caries. Logistic
      regression models were also used to examine the impact of several demographic
      characteristics and health behaviours on the presence of obesity and caries.
      RESULTS: The total sample included 347 children aged 5.10 +/- 0.31 (mean +/- SD).
      Deprivation had a significant impact on caries and BMI z-scores (p < 0.05).
      Neither BMI- nor waist circumference z-scores were shown to be significantly
      associated with dental caries. Among the neighbourhood characteristics examined,
      the percentage of people dependent on benefits was found to have a significant
      impact on caries rates (p < 0.05). Household's total annual income was inversely
      related to caries risk and parental educational level affected children's tooth
      brushing frequency. CONCLUSIONS: No associations between any measure of obesity
      and caries were found. However, deprivation affected both obesity and caries,
      thus highlighting the need to prioritise disadvantaged children in future
      prevention programmes.

PMID- 29454321
TI  - Safety and efficacy of temsirolimus as second line treatment for patients with
      recurrent bladder cancer.
AB  - BACKGROUND: Bladder cancer is the 7th cause of death from cancer in men and 10th
      in women. Metastatic patients have a poor prognosis with a median overall
      survival of 14 months. Until recently, vinflunine was the only second-line
      chemotherapy available for patients who relapse. Deregulation of the
      PI3K/AKT/mTOR pathway was observed in more than 40% of bladder tumors and
      suggested the use of mTOR as a target for the treatment of urothelial cancers.
      METHODS: This trial assessed the efficacy of temsirolimus in a homogenous cohort
      of patients with recurrent or metastatic bladder cancer following first-line
      chemotherapy. Efficacy was measured in terms of non-progression at two months
      according to the RECIST v1.1 criteria. Based on a two-stage optimal Simon's
      design, 15 non-progressions out of 51 evaluable patients were required to claim
      efficacy. Patients were treated at a weekly dose of 25 mg IV until progression,
      unacceptable toxicities or withdrawal. RESULTS: Among the 54 patients enrolled in
      the study between November 2009 and July 2014, 45 were assessable for the primary
      efficacy endpoint. A total of 22 (48.9%) non-progressions were observed at 2
      months with 3 partial responses and 19 stable diseases. Remarkably, 4 patients
      were treated for more than 30 weeks. Fifty patients experienced at least a
      related grade1/2 (94%) and twenty-eight patients (52.8%) a related grade 3/4
      adverse event. Eleven patients had to stop treatment for toxicity. This led to
      recruitment being halted by an independent data monitoring committee with regard
      to the risk-benefit balance and the fact that the primary objective was already
      met. CONCLUSIONS: While the positivity of this trial indicates a potential
      benefit of temsirolimus for a subset of bladder cancer patients who are
      refractory to first line platinum-based chemotherapy, the risk of adverse events
      associated with the use of this mTOR inhibitor would need to be considered when
      such an option is envisaged in this frail population of patients. It also remains
      to identify patients who will benefit the most from this targeted therapy. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT01827943 (trial registration
      date: October 29, 2012); Retrospectively registered.

PMID- 29454322
TI  - Using eHealth to engage and retain priority populations in the HIV treatment and
      care cascade in the Asia-Pacific region: a systematic review of literature.
AB  - BACKGROUND: The exponential growth in the reach and development of new
      technologies over the past decade means that mobile technologies and social media
      play an increasingly important role in service delivery models to maximise HIV
      testing and access to treatment and care. This systematic review examines the
      impact of electronic and mobile technologies in medical care (eHealth) in the
      linkage to and retention of priority populations in the HIV treatment and care
      cascade, focussing on the Asia-Pacific region. METHODS: The review was informed
      by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) statement from the Cochrane Collaboration guidelines. Both grey and
      published scientific literature from five different databases were searched for
      all original articles in English published from 2010 to 2017. Studies conducted
      outside the Asia-Pacific region or not including HIV priority populations were
      excluded. The methodological quality of studies included in the review was
      assessed using the Quality Assessment Tool for Quantitative Studies. RESULTS: The
      database search identified 7309 records. Of the 224 peer-reviewed articles
      identified for full text review, 16 studies from seven countries met inclusion
      criteria. Six cross sectional studies found evidence to support the use of
      eHealth, via text messages, instant messaging, social media and health promotion
      websites, to increase rates of HIV testing and re-testing among men who have sex
      with men (MSM). Evidence regarding the efficacy of eHealth interventions to
      improve antiretroviral treatment (ART) adherence was mixed, where one randomised
      controlled trial (RCT) showed significant benefit of weekly phone call reminders
      on improving ART adherence. Three further RCTs found that biofeedback eHealth
      interventions that provided estimated ART plasma concentration levels, showed
      promising results for ART adherence. CONCLUSIONS: This review found encouraging
      evidence about how eHealth can be used across the HIV treatment and care cascade
      in the Asia-Pacific region, including increasing HIV testing and re-testing in
      priority populations as well as ART adherence. eHealth interventions have an
      important role to play in the movement towards the end of AIDS, particularly to
      target harder-to-reach HIV priority populations, such as MSM.

PMID- 29454323
TI  - Autonomy and infant feeding decision-making among teenage mothers in a rural and
      urban setting in KwaZulu-Natal, South Africa.
AB  - BACKGROUND: The nutritional status of infants born to teenage mothers can be sub
      optimal compared to those born to older mothers. One contributing factor is
      inappropriate feeding practices adopted by teenage mothers. Little is known about
      how infant feeding decisions are made among teenage mothers, particularly in
      under resourced settings. In this study we prospectively explored autonomy and
      infant feeding decision-making among teenage mothers in a rural and urban setting
      in KwaZulu-Natal, South Africa. METHODS: This study adopted a qualitative
      longitudinal design. Thirty pregnant participants were recruited to the study
      cohort, from the catchment area of two hospitals (one urban and one rural).
      Participants were purposively selected to include teenagers, HIV positive, and
      working pregnant women. We report findings from ten teenage mothers, aged between
      15 and 19 years, who participated in the larger cohort (n = 5 rural; n = 5
      urban). Monthly in-depth interviews were conducted with participating mothers for
      6 months starting 2 weeks after delivery. All interviews were conducted in the
      local language, transcribed verbatim and translated into English. Data was coded
      using NVivo v10 and framework analysis was used. RESULTS: Findings from this
      study showed that teenage mothers had knowledge about recommended feeding
      practices. However, our findings suggest that these mothers were not involved in
      infant feeding decisions once they were at home, because infant feeding decision
      making was a role largely assumed by older mothers in the family. Further, the
      age of the mother and financial dependency diminished her autonomy and ability to
      influence feeding practices or challenge incorrect advice given at home. Most
      feeding advice shared by family members was inappropriate, leading to poor infant
      feeding practices among teenage mothers. Returning to school and fear of
      breastfeeding in public were also barriers to exclusive breastfeeding.
      CONCLUSION: Teenage mothers had a limited role in the infant feeding decision
      making process. Health workers have an important role to play in ensuring that
      knowledge about infant feeding is shared with the mother's family where infant
      feeding choices are made. This will improve support for teenage mothers, and may
      also positively impact on the nutritional status of children.

PMID- 29454324
TI  - Investigation of the anti-cataractogenic mechanisms of curcumin through in vivo
      and in vitro studies.
AB  - BACKGROUND: Cataract is the leading cause of blindness in elderly people
      worldwide, especially in developing countries. Studies to identify strategies
      that can prevent or retard cataract formation are urgently required. This study
      aimed to investigate the potential mechanism of the cytoprotective effects of
      curcumin in in vivo and in vitro experiments. METHODS: Male Wistar rats were
      randomly divided into three groups: the control group, the model group
      (administered 20 MUmol/kg sodium selenite), and the curcumin group (pretreated
      with 75 mg/kg body weight curcumin 24 h prior to the administration of sodium
      selenite). The expression levels of heat shock protein 70 (HSP70), the activities
      of 8-hydroxy-2-deoxyguanosine (8-OHdG), catalase (CAT), malondialdehyde (MDA),
      superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were assessed by
      using RT-PCR assay and ELISA. In addition, the cell viability, cell apoptosis,
      and cell cycle were assessed using a CCK-8 assay and flow cytometry in in vitro
      studies, followed by RT-PCR analysis to identify the mRNA expression levels of
      caspase 3, Bcl-2 associated X (Bax), B-cell lymphoma 2 (Bcl-2), cyclooxygenase
      (Cox-2), c-met, and Slug. RESULTS: Cataract was successfully established in rats
      of the model group and the curcumin group through intraperitoneal injection of
      sodium selenite. The expression levels of HSP70 and the activities of 8-OHdG and
      MDA in the curcumin group were decreased compared with those in the model group,
      whereas the activities of CAT, SOD, and GSH-Px were significantly higher than
      those in the model group (P < 0.05). In the in vitro studies, the cell viability
      and cell apoptosis significantly increased and decreased, respectively, in the
      curcumin group compared with the model group. Correspondingly, the mRNA
      expression of caspase-3, Bax, and Cox-2 was lower in the curcumin group than in
      the model group (P < 0.05). CONCLUSIONS: This study suggested that curcumin
      attenuated selenite-induced cataract through the reduction of the intracellular
      production of reactive oxygen species and the protection of cells from oxidative
      damage.

PMID- 29454325
TI  - Latent tuberculosis infection and associated risk indicators in pastoral
      communities in southern Ethiopia: a community based cross-sectional study.
AB  - BACKGROUND: Research pertaining to the community-based prevalence of latent
      tuberculosis infection (LTBI) is important to understand the magnitude of this
      infection. This study was conducted to estimate LTBI prevalence and to identify
      associated risk factors in the Omo Zone of Southern Ethiopia. METHODS: A
      community-based cross-sectional study was conducted in six South Omo districts
      from May 2015 to February 2016. The sample size was allocated to the study
      districts proportional to their population sizes. Participants were selected
      using a multi-stage sampling approach. A total of 497 adult pastoralists were
      recruited. Blood samples were collected from the study participants and screened
      for LTBI using a U.S. Food and Drug Administration approved interferon-gamma
      release assay (IGRA). Logistic regression was used to model the likelihood of
      LTBI occurrence and to identify risk factors associated with LTBI. RESULTS: The
      prevalence of LTBI was 50.5% (95% CI: 46%, 55%) with no significant gender
      difference (49.8% among males versus 51.2% among females; Chi-square (chi2) =
      0.10; P = 0.41) and marginally non-significant increasing trends with age (44.6%
      among those below 24 years and 59.7% in the age range of 45-64 years; chi2 =
      6.91; P = 0.075). Being residence of the Dasanech District (adjusted odds ratio,
      AOR = 2.62, 95% CI: 1.30, 5.28; P = 0.007) and having a habit of eating raw meat
      (AOR = 2.89, 95% CI: 1.09, 7.66; P = 0.033) were significantly associated with an
      increased odds of being positive for LTBI. A large family size (size of 5 to 10)
      has significant protective effect against associated a reduced odds of being
      positive for LTBI compared to a family size of below 5 (AOR = 0.65, 95% CI: 0.42,
      0.99; P = 0.045). CONCLUSIONS: A high prevalence of LTBI in the South Omo Zone
      raises the concern that elimination of TB in the pastoral communities of the
      region might be difficult. Screening for and testing individuals infected with
      TB, independent of symptoms, may be an effective way to minimize the risk of
      disease spread.

PMID- 29454326
TI  - Predictors of activity and participation across neurodegenerative conditions: a
      comparison of people with motor neurone disease, multiple sclerosis and
      Parkinson's disease.
AB  - BACKGROUND: Comparisons between neurological conditions have the potential to
      inform service providers by identifying particular areas of difficulty
      experienced by affected individuals. This study aimed to identify predictors of
      activity and participation in people with motor neurone disease (MND), people
      with multiple sclerosis (MS) and people with Parkinson's Disease (PD). METHODS:
      The Oxford Participation and Activities Questionnaire (Ox-PAQ) and Medical
      Outcomes Study 36-Item Short Form Survey (MOS SF-36) were administered by postal
      survey to 386 people with a confirmed diagnosis of MND, MS or PD. Data analyses
      focused on stepwise regression analyses in order to identify predictors of
      activity and participation in the three conditions assessed. RESULTS: Three
      hundred and thirty four participants completed the survey, a response rate of
      86.5%. Regression analyses identified multiple predictors of activity and
      participation dependent on Ox-PAQ domain and disease group, the most prominent
      being social and physical functioning as measured by the MOS SF-36. CONCLUSIONS:
      Results indicate that the physical and social consequences of neurological
      illness are of greatest relevance to people experiencing the conditions assessed.
      Whilst the largely inevitable physical implications of disease take hold,
      emphasis should be placed on the avoidance of social withdrawal and isolation,
      and the maintenance of social engagement should become a significant priority.

PMID- 29454328
TI  - Cap-preserving SMILE Enhancement Surgery.
AB  - BACKGROUND: Different enhancement procedures have been suggested for reduction of
      residual refractive errors after SMILE. The aim of this study is to evaluate an
      improved cap-preserving technique for enhancement after SMILE (Re-SMILE).
      METHODS: A retrospective case series was conducted at Eye subspecialty center,
      Cairo, Egypt on 9 eyes with myopia or myopic astigmatism (spherical equivalent -
      8.0 and - 12.0D). undergoing SMILE procedure and needed second interference. This
      was either because the more myopic meridian was more than - 10.0 D and therefore
      planned to have two-steps procedure (six eyes) or because of under correction
      needing enhancement (three eyes). Assessment after the primary SMILE procedure
      was conducted at 1 day, 1 week, 1 month and 3 months postoperatively. Assessment
      after Re-SMILE was conducted at 1 day, 1 week, 1 month, 3 months, 6 months and 1
      year postoperatively. The assessments included full ophthalmic examination,
      objective and subjective refraction, and rotating Scheimpflug camera imaging.
      RESULTS: Preoperatively, the mean refractive spherical equivalent (MRSE) values
      were: - 9.36 +/- 0. 89. After primary SMILE it was - 2.18 +/- 0.71. After Re
      SMILE it was - 0.13 +/- 0.68. MRSE was significantly improved after both
      procedures (P < 0.01). The safety index of primary SMILE cases was 1.65 +/- 0.62
      and for Re-SMILE 1.13 +/- 0.34 and the efficacy index was 1.14 +/- 0.24 after
      primary SMILE and 1.11 +/- 0.26 after Re-SMILE. CONCLUSION: Centered cap
      preserving Re-SMILE is an effective procedure in reducing residual refractive
      errors after primary SMILE in high myopes.

PMID- 29454329
TI  - Bilateral acute angle-closure glaucoma following tramadol subcutaneous
      administration.
AB  - BACKGROUND: To report a case of bilateral acute angle closure-glaucoma following
      the use of subcutaneous Tramadol. CASE PRESENTATION: A 42-year-old healthy man
      with unremarkable past medical and ocular history, was admitted to the Orthopedic
      Department for surgical treatment of a bilateral open fracture of the femur
      following a road accident. Three hoursafterTramadolsubcutaneous injection, the
      patient complained of a bilateral acute painful visual loss with persistent
      vomiting. An ocular examination showed bilateral acute angle-closure-glaucoma.
      The patient was treated with topical anti-glaucoma therapy and intravenous
      Mannitol 20%.After resolution of ocular hypertension attack, NdYag laser
      peripheral iridotomy was performed on both eyes. After a follow-up period of 7
      days visual acuity improved to 20/20 in both eyes and intraocular pressure
      returned to normal levels. CONCLUSIONS: This case highlights the risk of
      developing bilateral acute angle-closure glaucoma after Tramadol administration.

PMID- 29454327
TI  - Peer support to improve diabetes care: an implementation evaluation of the
      Australasian Peers for Progress Diabetes Program.
AB  - BACKGROUND: Several studies have now demonstrated the benefits of peer support in
      promoting diabetes control. The aim of this study is to evaluate the
      implementation of a cluster randomised controlled trial of a group-based, peer
      support program to improve diabetes self-management and thereby, diabetes control
      in people with Type 2 Diabetes in Victoria, Australia. METHODS: The intervention
      program was designed to address four key peer support functions i.e. 1)
      assistance in daily management, 2) social and emotional support, 3) regular
      linkage to clinical care, and 4) ongoing and sustained support to assist with the
      lifelong needs of diabetes self-care management. The intervention participants
      attended monthly group meetings facilitated by a trained peer leader for 12
      months. Data was collected on the intervention's reach, participation,
      implementation fidelity, groups' effectiveness and participants' perceived
      support and satisfaction with the intervention. The RE-AIM and PIPE frameworks
      were used to guide this evaluation. RESULTS: The trial reached a high proportion
      (79%) of its target population through mailed invitations. Out of a total of 441
      eligible individuals, 273 (61.9%) were willing to participate. The intervention
      fidelity was high (92.7%). The proportion of successful participants who
      demonstrated a reduction in 5 years cardiovascular disease risk score was 65.1
      and 44.8% in the intervention and control arm respectively. Ninety-four percent
      (94%) of the intervention participants stated that the program helped them manage
      their diabetes on a day to day basis. Overall, attending monthly group meetings
      provided 'a lot of support' to 57% and 'moderate' support to 34% of the
      participants. CONCLUSION: Peer support programs are feasible, acceptable and can
      be used to supplement treatment for patients motivated to improve behaviours
      related to diabetes. However, program planners need to focus on the participation
      component in designing future programs. The use of two evaluation frameworks
      allowed a comprehensive evaluation of the trial from the provider-, participant-
      and public health perspective. The learnings gained from this evaluation will
      guide and improve future implementation by improving program feasibility for
      adoption and acceptability among participants, and will ultimately increase the
      likelihood of program effectiveness for the participants. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000469213 .
      Registered 16 June 2009.

PMID- 29454330
TI  - Comparison of visceral, body fat indices and anthropometric measures in relation
      to chronic kidney disease among Chinese adults from a large scale cross-sectional
      study.
AB  - BACKGROUND: The aim of the study was to assess the association between chronic
      kidney disease (CKD) and obesity in predicting CKD among Chinese adults,
      distinguishing between 5 different adiposity indices: visceral fat index (VFI),
      percentage body fat (PBF), body mass index (BMI), waist circumference (WC) and
      waist-to-height ratio (WHtR). METHODS: A total of 29,516 participants aged 35
      years or above were selected using a stratified multistage random sampling method
      across China during 2012-2015. CKD was defined as an estimated glomerular
      filtration (eGFR) < 60 ml/min/1.72m2. RESULTS: The overall weighted prevalence of
      CKD was 3.94% (3.62% in males and 4.25% in females). All five adiposity indices
      had significant negative correlations to eGFR (P < 0.05). The area under the ROC
      (receiver operating characteristic) curves (AUC) for PBF was almost significantly
      larger than the other adiposity indices (P < 0.001). In addition, PBF yielded the
      highest Youden index in identifying CKD (male: 0.15; female: 0.20). In the
      logistic analysis, PBF had the highest crude odds ratios (ORs) in both males (OR:
      1.819, 95% CI 1.559-2.123) and females (OR: 2.268, 95% CI 1.980-2.597). After
      adjusted for age, smoking status, alcohol use, education level, marital status,
      rural vs. urban area, geographic regions, and diagnosis of hypertension, diabetes
      mellitus, myocardial infarction and stroke, the ORs on PBF remained significant
      for both genders (P < 0.05). CONCLUSIONS: Obesity is associated with an increased
      risk of CKD. Furthermore, PBF was a better predictor for identifying CKD than
      other adiposity indices (BMI, WC, WHtR, and VFI).

PMID- 29454331
TI  - The increasing importance of a continence nurse specialist to improve outcomes
      and save costs of urinary incontinence care: an analysis of future policy
      scenarios.
AB  - BACKGROUND: In an ageing population, it is inevitable to improve the management
      of care for community-dwelling elderly with incontinence. A previous study showed
      that implementation of the Optimum Continence Service Specification (OCSS) for
      urinary incontinence in community-dwelling elderly with four or more chronic
      diseases results in a reduction of urinary incontinence, an improved quality of
      life, and lower healthcare and lower societal costs. The aim of this study was to
      explore future consequences of the OCSS strategy of various healthcare policy
      scenarios in an ageing population. METHODS: We adapted a previously developed
      decision analytical model in which the OCSS new care strategy was operationalised
      as the appointment of a continence nurse specialist located within the general
      practice in The Netherlands. We used a societal perspective including healthcare
      costs (healthcare providers, treatment costs, insured containment products,
      insured home care), and societal costs (informal caregiving, containment products
      paid out-of-pocket, travelling expenses, home care paid out-of-pocket). All
      outcomes were computed over a three-year time period using two different base
      years (2014 and 2030). Settings for future policy scenarios were based on desk
      research and expert opinion. RESULTS: Our results show that implementation of the
      OSCC new care strategy for urinary incontinence would yield large health gains in
      community dwelling elderly (2030: 2592-2618 QALYs gained) and large cost-savings
      in The Netherlands (2030: health care perspective: ?32.4 Million - ?72.5 Million;
      societal perspective: ?182.0 Million - ?250.6 Million). Savings can be generated
      in different categories which depends on healthcare policy. The uncertainty
      analyses and extreme case scenarios showed the robustness of the results.
      CONCLUSIONS: Implementation of the OCSS new care strategy for urinary
      incontinence results in an improvement in the quality of life of community
      dwelling elderly, a reduction of the costs for payers and affected elderly, and a
      reduction in time invested by carers. Various realistic policy scenarios even
      forecast larger health gains and cost-savings in the future. More importantly,
      the longer the implementation is postponed the larger the savings foregone. The
      future organisation of healthcare affects the category in which the greatest
      savings will be generated.

PMID- 29454332
TI  - Do pregnancies reduce iron overload in HFE hemochromatosis women? results from an
      observational prospective study.
AB  - BACKGROUND: HFE hemochromatosis is an inborn error of iron metabolism linked to a
      defect in the regulation of hepcidin synthesis. This autosomal recessive disease
      typically manifests later in women than men. Although it is commonly stated that
      pregnancy is, with menses, one of the factors that offsets iron accumulation in
      women, no epidemiological study has yet supported this hypothesis. The aim of our
      study was to evaluate the influence of pregnancy on expression of the predominant
      HFE p.[Cys282Tyr];[Cys282Tyr] genotype. METHODS: One hundred and forty
      p.Cys282Tyr homozygous women enrolled in a phlebotomy program between 2004 and
      2011 at a blood centre in western Brittany (France) were included in the study.
      After checking whether the disease expression was delayed in women than in men in
      our study, the association between pregnancy and iron overload was assessed using
      multivariable regression analysis. RESULTS: Our study confirms that women with
      HFE hemochromatosis were diagnosed later than men cared for during the same
      period (52.6 vs. 47.4 y., P < 0.001). Compared to no pregnancy, having at least
      one pregnancy was not associated with lower iron markers. In contrast, the amount
      of iron removed by phlebotomies appeared significantly higher in women who had at
      least one pregnancy (ebeta = 1.50, P = 0.047). This relationship disappeared
      after adjustment for confounding factors (ebeta = 1.35, P = 0.088). CONCLUSIONS:
      Our study shows that pregnancy status has no impact on iron markers level, and is
      not in favour of pregnancy being a protective factor in progressive iron
      accumulation. Our results are consistent with recent experimental data suggesting
      that the difference in disease expression observed between men and women may be
      explained by other factors such as hormones.

PMID- 29454334
TI  - Predictors of working beyond retirement in older workers with and without a
      chronic disease - results from data linkage of Dutch questionnaire and registry
      data.
AB  - BACKGROUND: An increasing number of retirees continue to work beyond retirement
      despite being eligible to retire. As the prevalence of chronic disease increases
      with age, working beyond retirement may go along with having a chronic disease.
      Working beyond retirement may be different for retirees with and without chronic
      disease. We aim to investigate whether demographic, socioeconomic and work
      characteristics, health and social factors predict working beyond retirement, in
      workers with and without a chronic disease. METHODS: Employees aged 56-64 years
      were selected from the Study on Transitions in Employment, Ability and Motivation
      (N = 1125). Questionnaire data on demographic and work characteristics, health,
      social factors, and working beyond retirement were linked to registry data from
      Statistics Netherlands on socioeconomic characteristics. Separate prediction
      models were built for retirees with and without chronic disease using
      multivariate logistic regression analyses. RESULTS: Workers without chronic
      disease were more likely to work beyond retirement compared to workers with
      chronic disease (27% vs 23%). In retirees with chronic disease, work and health
      factors predicted working beyond retirement, while in retirees without a chronic
      disease, work, health and social factors predicted working beyond retirement. In
      the final model for workers with chronic disease, healthcare work, better
      physical health, higher body height, lower physical load and no permanent
      contract were positively predictive of working beyond retirement. In the final
      model for workers without chronic disease, feeling full of life and being
      intensively physically active for > = 2 days per week were positively predictive
      of working beyond retirement; while manual labor, better recovery, and a partner
      who did not support working until the statutory retirement age, were negatively
      predictive of working beyond retirement. CONCLUSIONS: Work and health factors
      independently predicted working beyond retirement in workers with and without
      chronic disease, whereas social factors only did so among workers without chronic
      disease. Demographic and socioeconomic characteristics did not independently
      contribute to prediction of working beyond retirement in any group. As prediction
      of working beyond retirement was more difficult among workers with a chronic
      disease, future research is needed in this group.

PMID- 29454333
TI  - Comparative study of ultrasound-guided paravertebral block versus intravenous
      tramadol for postoperative pain control in percutaneous nephrolithotomy.
AB  - BACKGROUND: Percutaneous nephrolithotomy (PCNL) is a minimally invasive surgical
      procedure for renal calculi, and nephrostomy tubes lead to postoperative pain
      after PCNL. Regional techniques (e.g., epidural analgesia and peripheral blocks)
      and opioids are applied for postoperative pain treatment. The aim of this study
      was to compare effectiveness of ultrasound-guided paravertebral block (PVB) and
      tramadol on postoperative pain in patients who underwent PCNL. METHOD: Fifty
      three patients were included in this prospective randomized study. The patients
      were allocated into two groups: the PVB group (group P, n = 26) and the tramadol
      group (group T, n = 27). All patients were administered standard general
      anaesthesia. Ultrasound-guided PVB was performed at the T11- L1 levels using 0.5%
      bupivacaine for a total dose of 15 mL in group P. Patients in group T were
      intravenously administered a loading dose of 1 mg/kg tramadol. Patients in both
      groups were given patient-controlled analgesia. Haemodynamic parameters, visual
      analogue scale (VAS) scores, side effects, and complications, tramadol
      consumption and additional analgesic requirements of the patients were recorded
      after surgery. RESULTS: Haemodynamic parameters were statistically similar
      between the groups. The VAS in group P were statistically lower than in group T.
      In the 24-h period after surgery, total PCA tramadol consumption was
      statistically lower in group P than in group T. The use of supplemental analgesic
      in group T was higher than in group P. CONCLUSIONS: Ultrasound-guided PVB was
      found to be an effective analgesia compared to tramadol, and no additional
      complications were encountered. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02412930 , date of registration: March 27, 2015, retrospectively registered.

PMID- 29454335
TI  - Earliella scabrosa-associated postoperative Endophthalmitis after
      Phacoemulsification with intraocular lens implantation: a case report.
AB  - BACKGROUND: Postoperative endophthalmitis after cataract surgery is a severe eye
      infection that can lead to irreversible blindness in the affected eye. The
      characteristics, treatment and prognosis of this disease vary because of its
      association with different pathogens. Here, we report what is possibly the first
      case of endophthalmitis after cataract surgery to be associated with the rare
      pathogen Earliella scabrosa. CASE PRESENTATION: A 56-year-old man from Hainan
      Island (China) with a history of phacoemulsification and type II diabetes
      mellitus underwent intraocular lens (IOL) implantation. He later presented with
      progressive endophthalmitis in his right eye. IOL explantation with capsular bag
      removal and a 23G pars plana vitrectomy combined with a silicone oil tamponade
      was performed. The infection was cleared without recurrence, and the patient's
      visual acuity improved from light perception to 20/200 in the right eye. An in
      vitro culture determined that the causative pathogen was Earliella scabrosa, and
      this result was confirmed by an internal transcribed spacer (ITS) sequence
      analysis. CONCLUSION: Earliella scabrosa has never been reported as an infectious
      agent in human eyes, and its clinical significance remains unknown. Here, we
      report a rare case of Earliella scabrosa-associated endophthalmitis after
      cataract surgery. The fungal infection presented as an acute attack and was
      successfully treated with vitrectomy.

PMID- 29454336
TI  - Change in physical activity level and clinical outcomes in older adults with knee
      pain: a secondary analysis from a randomised controlled trial.
AB  - BACKGROUND: Exercise interventions improve clinical outcomes of pain and function
      in adults with knee pain due to osteoarthritis and higher levels of physical
      activity are associated with lower severity of pain and higher levels of physical
      functioning in older adults with knee osteoarthritis in cross-sectional studies.
      However, to date no studies have investigated if change in physical activity
      level during exercise interventions can explain clinical outcomes of pain and
      function. This study aimed to investigate if change in physical activity during
      exercise interventions is associated with future pain and physical function in
      older adults with knee pain. METHODS: Secondary longitudinal data analyses of a
      three armed exercise intervention randomised controlled trial. Participants were
      adults with knee pain attributed to osteoarthritis, over the age of 45 years old
      (n = 514) from Primary Care Services in the Midlands and Northwest regions of
      England. Crude and adjusted associations between absolute change in physical
      activity from baseline to 3 months (measured by the self-report Physical Activity
      Scale for the Elderly (PASE)) and i) pain ii) physical function (Western Ontario
      and McMaster Universities Osteoarthritis Index) and iii) treatment response
      (OMERACT-OARSI responder criteria) at 3 and 6 months follow-up were investigated
      using linear and logistic regression. RESULTS: Change in physical activity level
      was not associated with future pain, function or treatment response outcomes in
      crude or adjusted models at 3 or 6 months (P > 0.05). A 10 point increase in PASE
      was not associated with pain beta = - 0.01 (- 0.05, 0.02), physical function beta
      = - 0.09 (- 0.19, 0.02) or likelihood (odds ratio) of treatment response 1.02
      (0.99, 1.04) at 3 months adjusting for sociodemographics, clinical covariates and
      the trial intervention arm. Findings were similar for 6 month outcome models.
      CONCLUSIONS: Change in physical activity did not explain future clinical outcomes
      of pain and function in this study. Other factors may be responsible for clinical
      improvements following exercise interventions. However, the PASE may not be
      sufficiently responsive to measure change in physical activity level. We also
      recommend further investigation into the responsiveness of commonly used physical
      activity measures. TRIAL REGISTRATION: ( ISRCTN93634563 ). Registered 29th
      September 2011.

PMID- 29454337
TI  - The second patient? Family members of cancer patients and their role in end-of
      life decision making.
AB  - BACKGROUND: Family members are important companions of severely ill patients with
      cancer. However, studies about the desirability and difficulties of integrating
      relatives in the decision-making process are rare in oncology. This qualitative
      study explores the family role in decisions to limit treatment near the end of
      life from the professionals' point of view. METHODS: Qualitative in-depth
      interviews were conducted with oncologists (n = 12) and nurses (n = 6) working at
      the Department of Hematology/Oncology at the University Hospital in Munich,
      Germany. The data were analyzed using a descriptive qualitative methodology and
      discussed from a medical ethics perspective. RESULTS: Four major themes played a
      central role in the perception of the medical staff in regard to family members.
      (1) Family impact on patients' treatment preferences. (2) Strong family wish for
      further treatment. (3) Emotional distress of the family related to the
      involvement in end-of-life decision-making. (4) Importance of knowing family
      structures. CONCLUSIONS: The important role of the family members in patients'
      disease process is recognized by oncologists and oncology nurses. However, this
      does not seem to lead to an early involvement of the family members. Developing
      and establishing a systematic assessment of family members' needs and wishes in
      order to provide a specific-tailored support should become a priority for
      interdisciplinary clinical research in the near future.

PMID- 29454338
TI  - "Factors associated with non-small cell lung cancer treatment costs in a
      Brazilian public hospital".
AB  - BACKGROUND: The present study estimated the cost of advanced non-small cell lung
      cancer care for a cohort of 251 patients enrolled in a Brazilian public hospital
      and identified factors associated with the cost of treating the disease,
      considering sociodemographic, clinical and behavioral characteristics of
      patients, service utilization patterns and survival time. METHODS: Estimates were
      obtained from the survey of direct medical cost per patient from the hospital's
      perspective. Data was collected from medical records and available hospital
      information systems. The ordinary least squares (OLS) method with logarithmic
      transformation of the dependent variable for the analysis of cost predictors was
      used to take into account the positive skewness of the costs distribution.
      RESULTS: The average cost of NSCLC was US$ 5647 for patients, with 71% of costs
      being associated to outpatient care. The main components of cost were daily
      hospital bed stay (22.6%), radiotherapy (15.5%) and chemotherapy (38.5%). The OLS
      model reported that, with 5% significance level, patients with higher levels of
      education, with better physical performance and less advanced disease have higher
      treatment costs. After controlling for the patient's survival time, only
      education and service utilization patterns were statistically significant.
      Individuals who were hospitalized or made use of radiotherapy or chemotherapy had
      higher costs. The use of these outpatient and hospital services explained most of
      the treatment cost variation, with a significant increase of the adjusted R2 of
      0.111 to 0.449 after incorporation of these variables in the model. The
      explanatory power of the complete model reached 62%. CONCLUSIONS: Inequities in
      disease treatment costs were observed, pointing to the need for strategies that
      reduce lower socioeconomic status and population's hurdles to accessing cancer
      care services.

PMID- 29454339
TI  - A structural preview of aquaporin 8 via homology modeling of seven vertebrate
      isoforms.
AB  - BACKGROUND: Aquaporins (AQPs) facilitate the passage of small neutral polar
      molecules across membranes of the cell. In animals there are four distinct AQP
      subfamilies, whereof AQP8 homologues constitute one of the smallest subfamilies
      with just one member in man. AQP8 conducts water, ammonia, urea, glycerol and
      H2O2 through various membranes of animal cells. This passive channel has been
      connected to a number of phenomena, such as volume change of mitochondria,
      ammonia neurotoxicity, and mitochondrial dysfunction related to oxidative stress.
      Currently, there is no experimentally determined structure of an AQP8, hence the
      structural understanding of this subfamily is limited. The recently solved
      structure of the plant AQP, AtTIP2;1, which has structural and functional
      features in common with AQP8s, has opened up for construction of homology models
      that are likely to be more accurate than previous models. RESULTS: Here we
      present homology models of seven vertebrate AQP8s. Modeling based on the AtTIP2;1
      structure alone resulted in reasonable models except for the pore being blocked
      by a phenylalanine that is not present in AtTIP2;1. To achieve an open pore,
      these models were supplemented with models based on the bacterial water specific
      AQP, EcAqpZ, creating a chimeric monomeric model for each AQP8 isoform. The
      selectivity filter (also named the aromatic/arginine region), which defines the
      permeant substrate profile, comprises five amino acid residues in AtTIP2;1,
      including a histidine coming from loop C. Compared to AtTIP2;1, the selectivity
      filters of modelled AQP8s only deviates in that they are slightly more narrow and
      more hydrophobic due to a phenylalanine replacing the histidine from loop C.
      Interestingly, the models do not exclude the existence of a side pore beneath
      loop C similar to that described in the structure of AtTIP2;1. CONCLUSIONS: Our
      models concur that AQP8s are likely to have an AtTIP2;1-like selectivity filter.
      The detailed description of the expected configuration of residues in the
      selectivity filters of AQP8s provides an excellent starting point for planning of
      as well as rationalizing the outcome of mutational studies. Our strategy to
      compile hybrid models based on several templates may prove useful also for other
      AQPs for which structural information is limited.

PMID- 29454340
TI  - Risk perception of blood transfusions - a comparison of patients and allied
      healthcare professionals.
AB  - BACKGROUND: Due to an increasing demand in health care services plans to
      substitute selective physician-conducted medical activities have become
      attractive. Because administration of a blood transfusion is a highly
      standardized procedure, it might be evaluated if obtaining a patient's consent
      for a blood transfusion can be delegated to allied healthcare professionals.
      Physicians and patients perceive risks of transfusions differently. However, it
      is unknown how allied healthcare professionals perceive risks of transfusion
      associated adverse events. METHODS: Patients (n = 506) and allied healthcare
      professionals (n = 185) of an academic teaching hospital were asked to quantify
      their concerns about transfusions including five predefined transfusion
      associated risks and their incidences. RESULTS: Blood transfusions were
      considered to be generally harmful by 10.9% of patients and 14.6% of caregivers
      (P = 0.180). Among all surveyed patients, 36.8% were worried about infection
      transmissions (caregivers: 27.6%; P = 0.024). Compared to 5.4% of caregivers,
      13.6% of patients believed infection-transmission was a frequent complication (P
      = 0.003). Caregivers ranked the risks of receiving an AB0-mismatch transfusion
      (caregivers: 29.7% vs. PATIENTS: 19.2%, P = 0.003) or a transfusion-associated
      allergic reaction (caregivers: 17.3% vs. PATIENTS: 11.1%, P = 0.030)
      significantly higher than patients and were aware of the high incidence of
      transfusion-associated fever (caregivers: 17.8% vs. PATIENTS: 8.3%, P < 0.001).
      CONCLUSION: A significant part of interviewees perceived transfusions as a
      general health hazard. Patients perceived infection-transmissions as the most
      frequent and greatest transfusion-associated threat while caregivers focused on
      fatal AB0-mismatch transfusions and allergic reactions. Understanding the
      patients' main concerns about blood transfusions and considering that these
      concerns might differ from the view of healthcare professionals might improve the
      process of shared decision making.

PMID- 29454341
TI  - Treatment of depression with Chai Hu Shu Gan San: a systematic review and meta
      analysis of 42 randomized controlled trials.
AB  - BACKGROUND: Depression is a common mental disorder. Chai Hu Shu Gan San, a
      traditional Chinese medicine, is used to treat depression empirically. We present
      a systematic review and meta-analysis of the therapeutic efficacy and safety of
      Chai Hu Shu Gan San in treating depression. METHODS: Several databases, including
      PubMed, China National Knowledge Internet, Wanfang, Chongqing VIP, and the
      Cochrane library, were systematically searched from their date of foundation to
      January 1, 2017. In this review, wehave included randomized control trials that
      compared Chai Hu Shu Gan San (or its combination with a regular Western medicine)
      with a regular Western medicine alone for the treatment of depression. Two
      investigators independently extracted and analyzed the data using RevMan 5.2.0
      software. Mean difference (with a 95% confidence interval) was used as efficacy
      indices for outcomes. RESULTS: We included 42 studies involving 3234 patients
      with depression in 15 different types of diseases. Meta analyses showed better
      effect of Chai Hu Shu Gan San than fluoxetine for pure depression (MD = - 1.59,
      from - 2.82 to - 0.37, 4 trials, I2 = 26%), for post-stroke depression (MD = -
      4.20, from - 6.20 to - 2.19, 7 trials, I2 = 96%), and for postpartum depression
      (MD = - 4.10, from - 7.48 to - 0.72 7 trials, I2 = 86%). None of the articles
      reported severe adverse events of oral administration of Chai Hu Shu Gan San.
      Furthermore, any adverse effects of using Chai Hu Shu Gan San alone were fewer
      than those of regular Western medicines. CONCLUSIONS: This review found that Chai
      Hu Shu Gan San has some advantages in treating depression, especially post-stroke
      depression and post-partum depression. A meticulously designed and conducted
      randomized control trial is needed for further evaluation.

PMID- 29454342
TI  - Social support for patients undergoing liver transplantation in a Public
      University Hospital.
AB  - BACKGROUND: Several diseases may lead to the need for liver transplantation due
      to progressive organ damage until the onset of cirrhosis, resulting in changes in
      interpersonal relationships. Social Support for transplant candidates is an
      important variable, providing them with psychological and social well-being. This
      study aims to assess social support in chronic hepatic patients, waiting for
      liver transplantation. METHODS: A cross-sectional study was conducted with 119
      patients, for convenience sampling, from the liver transplant waiting list at a
      Brazilian University Hospital Outpatients. The information was collected through
      semistructured questionnaires, in four stages: 1) socioeconomic and demographic
      information 2) clinical aspects 3) feelings 4) Social Support Network Inventory
      (SSNI), to Brazilian Portuguese. The statistical analysis was conducted using
      ANOVA and multivariate linear regression analysis to evaluate the relationship
      between the scales of social support and the collected co-variables. RESULTS:
      Average age was 50.2 +/- 11.6, and 87 (73.1%) were men. Patients with alcohol and
      virus liver disease etiology had the same frequency of 28%. The MELD, without
      extrapoints, was 16.7 +/- 4.9. Global social support family score was 3.72 +/-
      0.39, and Cronbach's alpha = 0.79. The multivariate analysis presented the
      following associations, age = [- 0.010 (95% CI = - 0.010 - -0.010); P = 0.001],
      etiology of hepatic disease = [- 0.212 (95% CI = - 0.37 - -0.05); P = 0.009],
      happiness = [- 0.214(95% CI = - 0.33 - -0.09) P = 0.001) and aggressiveness =
      [0.172 (95% CI = 0.040-0.030); P = 0.010). CONCLUSIONS: The social support was
      greater when the patients were younger (18 to 30 years). Patients with alcoholic
      cirrhosis, regardless of whether or not they were associated with virus, had less
      social support. As for feelings, the absence of happiness and the presence of
      aggressiveness showed a negative effect on social support.

PMID- 29454343
TI  - Systematic development and adjustment of the German version of the Supportive and
      Palliative Care Indicators Tool (SPICT-DE).
AB  - BACKGROUND: The Supportive and Palliative Care Indicators tool (SPICT) supports
      the identification of patients with potential palliative care (PC) needs. An
      Austrian-German expert group translated SPICT into German (SPICT-DE) in 2014. The
      aim of this study was the systematic development, refinement, and testing of
      SPICT-DE for its application in primary care (general practice). METHODS: SPICT
      DE was developed by a multiprofessional research team according to the TRAPD
      model: translation, review, adjudication, pretesting and documentation. In a
      pretest, five general practitioners (GPs) rated four case vignettes of patients
      with different PC needs. GPs were asked to assess whether each patient might
      benefit from PC or not (I) based on their subjective appraisal ("usual practice")
      and (II) by using SPICT-DE. After further refinement, two focus groups with 28
      GPs (68% with a further qualification in PC) were conducted to test SPICT-DE.
      Again, participants rated two selected case vignettes (I) based on their
      subjective appraisal and (II) by using SPICT-DE. Afterwards, participants
      reflected the suitability of SPICT-DE for use in their daily practice routine
      within the German primary care system. Quantitative data were analysed with
      descriptive statistics and non-parametric tests for small samples. Qualitative
      data were analysed by conventional content analysis. Focus group discussion was
      analysed combining formal and conventional content analysis. RESULTS: Compared to
      the spontaneous rating of the case vignettes based on subjective appraisal,
      participants in both the pretest and the focus groups considered PC more often as
      being beneficial for the patients described in the case vignettes when using
      SPICT-DE. Participants in the focus groups agreed that SPICT-DE includes all
      relevant indicators necessary for an adequate clinical identification of patients
      who might benefit from PC. CONCLUSIONS: SPICT-DE supports the identification of
      patients who might benefit from PC and seems suitable for routine application in
      general practice in Germany. The systematic development, refinement, and testing
      of SPICT-DE in this study was successfully completed by using a multiprofessional
      and participatory approach.

PMID- 29454344
TI  - Validation of a core patient-reported-outcome measure set for operationalizing
      success in multimodal pain therapy: useful for depicting long-term success?
AB  - BACKGROUND: The study aims to validate a previously developed and published
      combined success criterion for patients after multimodal pain therapy (Donath et
      al., BMC Health Serv Res 15:272, 2015). The criterion classifies treated patients
      as successful in the long term on the basis of pain severity, disability through
      pain, depressiveness, and health-related quality of life. METHODS: Routine
      longitudinal data of 135 pain patients treated with multimodal pain therapy in
      2014-2015 at the Interdisciplinary Pain Center of the University Clinic Erlangen
      were available at baseline, therapy start, therapy end, and 12 months after
      treatment. Patients were, on average, 51.0 (SD 11.1) years old and to 63.7%
      female, two thirds were employed (66.7%). We conducted an analysis of concurrent
      validity (with: pain severity, disability through pain, depressiveness, mental
      and physical quality of life), criterion validity (with disability days, self
      rated success), convergent validity (with stress, anxiety, well-being), and
      discriminant validity (with chronicity of pain, comorbidity), objectivity, and
      reliability. Statistically, descriptive and inference statistics, graphical
      methods and MANOVAs were used. RESULTS: Patients classified as successful had
      significantly better values on the 5 variables demonstrating concurrent validity
      (all p < .001), significantly fewer Disability days (M = 15.31 (SD = 23.15) vs. M
      = 26.75 (SD = 29.15)); t (133) = 2.308; p = .024, less Anxiety (Pillai-Spur: F
      (3, 131) = 2.972, p = .034), less Stress (Pillai-Spur: F (3, 131) = 9.907, p <
      .001), and better Well-being (Pillai-Spur: F (3, 131) = 9.594, p < .001) 12
      months after treatment than patients classified as not successful. The Spearman
      correlation between success classification and Chronicity stage was .094 (p =
      .280). CONCLUSION: We demonstrated the validity of the combined success criterion
      with long-term data in addition to confirming the reliability and objectivity of
      the criterion. Future research might consider identifying predictors of success
      in multi-modal pain therapy.

PMID- 29454345
TI  - Associations of total and type-specific physical activity with mortality in
      chronic obstructive pulmonary disease: a population-based cohort study.
AB  - BACKGROUND: Regular physical activity is recommended for all people with chronic
      obstructive pulmonary disease (COPD), but the dose of physical activity required
      to gain mortality benefit in this population is not yet known. This aim of this
      study was to examine the associations of total and type-specific physical
      activity with mortality risk in people with COPD. METHODS: People with COPD aged
      >=40 years were identified from the 1997 Health Survey for England and the 1998
      and 2003 Scottish Health Survey cohorts. Self-reported total physical activity,
      moderate-vigorous intensity physical activity (MVPA), walking, domestic physical
      activity, and sport/exercise were assessed at baseline. Cox proportional hazards
      models were used to examine the associations between physical activity and
      mortality risk. RESULTS: Two thousand three hundred ninety-eight participants
      with COPD were included in the analysis and followed up for a mean 8.5 (SD 3.9)
      years. For both total physical activity and MVPA, we observed dose-response
      associations with all-cause and cardiovascular disease (CVD) mortality risk, and
      with respiratory mortality risk to a lesser extent. Compared to those who
      reported no physical activity, participants who met the physical activity
      guidelines demonstrated the greatest reductions in all-cause (HR 0.56, 95% CI
      0.45-0.69), CVD (HR 0.48, 95% CI 0.32-0.71) and respiratory mortality risk (HR
      0.40, 95% CI 0.24-0.67). Participants who reported a level of physical activity
      of at least half the dosage recommended by the guidelines also had a reduced risk
      of all-cause (HR 0.75, 95% CI 0.56-1.00) and CVD mortality (HR 0.48, 95% CI 0.26
      0.88). Dose-response associations with mortality risk were demonstrated for
      walking and sport/exercise, but not domestic physical activity. CONCLUSIONS: We
      found a dose-response association between physical activity and all-cause and CVD
      mortality risk in people with COPD, with protective effects appearing at levels
      considerably lower than the general physical activity recommendations. People
      with COPD may benefit from engagement in low levels of physical activity,
      particularly walking and structured exercise.

PMID- 29454346
TI  - Agrobacterium-mediated and electroporation-mediated transformation of
      Chlamydomonas reinhardtii: a comparative study.
AB  - BACKGROUND: Chlamydomonas reinhardtii is an unicellular green alga used for
      functional genomics studies and heterologous protein expression. A major
      hindrance in these studies is the low level and instability of expression of
      nuclear transgenes, due to their rearrangement and/or silencing over time.
      RESULTS: We constructed dedicated vectors for Agrobacterium-mediated
      transformation carrying, within the T-DNA borders, the Paromomycin (Paro)
      selectable marker and an expression cassette containing the Luciferase (Luc)
      reporter gene. These vectors and newly developed co-cultivation methods were used
      to compare the efficiency, stability and insertion sites of Agrobacterium- versus
      electroporation-mediated transformation. The influence of different
      transformation methods, of the cell wall, of the virulence of different
      Agrobacterium strains, and of transgene orientation with respect to T-DNA borders
      were assessed. False positive transformants were more frequent in Agrobacterium
      mediated transformation compared to electroporation, compensating for the
      slightly lower proportion of silenced transformants observed in Agrobacterium
      mediated transformation than in electroporation. The proportion of silenced
      transformants remained stable after 20 cycles of subculture in selective medium.
      Next generation sequencing confirmed the nuclear insertion points, which occurred
      in exons or untraslated regions (UTRs) for 10 out of 10 Agrobacterium-mediated
      and 9 out of 13 of electroporation-mediated insertions. Electroporation also
      resulted in higher numbers of insertions at multiple loci. CONCLUSIONS: Due to
      its labor-intensive nature, Agrobacterium transformation of Chlamydomonas does
      not present significant advantages over electroporation, with the possible
      exception of its use in insertional mutagenesis, due to the higher proportion of
      within-gene, single-locus insertions. Our data indirectly support the hypothesis
      that rearrangement of transforming DNA occurs in the Chlamydomonas cell, rather
      than in the extracellular space as previously proposed.

PMID- 29454347
TI  - Oncology nurses' beliefs and attitudes towards the double-check of chemotherapy
      medications: a cross-sectional survey study.
AB  - BACKGROUND: Double-checking medications is a widely used strategy to enhance safe
      medication administration in oncology, but there is little evidence to support
      its effectiveness. The proliferated use of double-checking may be explained by
      positive attitudes towards checking among nurses. This study investigated
      oncology nurses' beliefs towards double-checking medication, its relation to
      beliefs about safety and the influence of nurses' level of experience and
      proximity to clinical care. METHODS: This was a survey of all oncology nurses in
      three Swiss hospitals. The questionnaire contained 41 items on 6 domains.
      Responses were recorded using a 7-point Likert scale. Multiple regression
      analysis was used to identify factors linked to strong beliefs in the
      effectiveness of double-checking. RESULTS: Overall, 274 (70%) out of 389 nurses
      responded (91% female, mean age 37 (standard deviation = 10)). Nurses reported
      very strong beliefs in the effectiveness and utility of double-checking. They
      were also confident about their own performance in double-checking. Nurses widely
      believed that double checking produced safety (e.g., 86% believed errors of
      individuals could be intercepted with double-checks). In contrast, some
      limitations of double-checking were also recognized, e.g., 33% of nurses reported
      that double checking caused frequent interruptions and 28% reported that double
      checking was done superficially in their unit. Regression analysis revealed that
      beliefs in effectiveness of double-checking were mainly associated with beliefs
      in safety production (p < 0.001). Nurses with experience in barcode scanning held
      less strong beliefs in effectiveness of double-checking (p = 0.006). In contrast
      to our expectations, there were no differences in beliefs between any
      professional sub-groups. CONCLUSION: The widespread and strong believe in the
      effectiveness of double-checking is linked to beliefs about safety production and
      co-exists with acknowledgement of the major disadvantages of double-checking by
      humans. These results are important factors to consider when any existing
      procedures are adapted or new checking procedures are implemented.

PMID- 29454348
TI  - Rational engineering of Streptomyces albus J1074 for the overexpression of
      secondary metabolite gene clusters.
AB  - BACKGROUND: Genome sequencing revealed that Streptomyces sp. can dedicate up to ~
      10% of their genomes for the biosynthesis of bioactive secondary metabolites.
      However, the majority of these biosynthetic gene clusters are only weakly
      expressed or not at all. Indeed, the biosynthesis of natural products is highly
      regulated through integrating multiple nutritional and environmental signals
      perceived by pleiotropic and pathway-specific transcriptional regulators.
      Although pathway-specific refactoring has been a proved, productive approach for
      the activation of individual gene clusters, the construction of a global super
      host strain by targeting pleiotropic-specific genes for the expression of
      multiple diverse gene clusters is an attractive approach. RESULTS: Streptomyces
      albus J1074 is a gifted heterologous host. To further improve its secondary
      metabolite expression capability, we rationally engineered the host by targeting
      genes affecting NADPH availability, precursor flux, cell growth and biosynthetic
      gene transcriptional activation. These studies led to the activation of the
      native paulomycin pathway in engineered S. albus strains and importantly the
      upregulated expression of the heterologous actinorhodin gene cluster.
      CONCLUSIONS: Rational engineering of Streptomyces albus J1074 yielded a series of
      mutants with improved capabilities for native and heterologous expression of
      secondary metabolite gene clusters.

PMID- 29454349
TI  - SGEF is a potential prognostic and therapeutic target for lung adenocarcinoma.
AB  - BACKGROUND: SH3-containing guanine nucleotide exchange factor (SGEF), a RhoG
      specific guanine nucleotide exchange factor (GEF), was consider as a key signal
      that determines cancer cell invasion. Although SGEF has been considered to highly
      express in glioma and prostate cancer. However, it is not well illustrated in
      LAC. METHODS: In this experiment, expression of SGEF was detected in 92 LAC and
      corresponding normal tissue samples by immunohistochemistry. In addition, we
      evaluated the invasion and migration of lung adenocarcinoma cells by the gain and
      loss of SGEF expression. Furthermore, RhoG activity was measured by GST pull-down
      assay. RESULTS: SGEF is highly expressed in LAC tissues than in normal lung
      tissues and was associated with the TNM stage. Lung adenocarcinoma patients with
      low SGEF subgroup had longer overall survival compared to those with high
      expression. Furthermore, univariate analysis showed that SGEF expression was an
      independent prognostic factor for overall survival in lung adenocarcinoma.
      Silencing of SGEF effectively suppressed the invasion and migration of human lung
      adenocarcinoma cells in vitro by inhibiting RhoG activity, and over-expression of
      SGEF could reverse this phenomena. CONCLUSION: SGEF is a novel prognostic target
      in human lung adenocarcinoma.

PMID- 29454350
TI  - Application of four-dimension criteria to assess rigour of qualitative research
      in emergency medicine.
AB  - BACKGROUND: The main objective of this methodological manuscript was to
      illustrate the role of using qualitative research in emergency settings. We
      outline rigorous criteria applied to a qualitative study assessing perceptions
      and experiences of staff working in Australian emergency departments. METHODS: We
      used an integrated mixed-methodology framework to identify different perspectives
      and experiences of emergency department staff during the implementation of a time
      target government policy. The qualitative study comprised interviews from 119
      participants across 16 hospitals. The interviews were conducted in 2015-2016 and
      the data were managed using NVivo version 11. We conducted the analysis in three
      stages, namely: conceptual framework, comparison and contrast and hypothesis
      development. We concluded with the implementation of the four-dimension criteria
      (credibility, dependability, confirmability and transferability) to assess the
      robustness of the study, RESULTS: We adapted four-dimension criteria to assess
      the rigour of a large-scale qualitative research in the emergency department
      context. The criteria comprised strategies such as building the research team;
      preparing data collection guidelines; defining and obtaining adequate
      participation; reaching data saturation and ensuring high levels of consistency
      and inter-coder agreement. CONCLUSION: Based on the findings, the proposed
      framework satisfied the four-dimension criteria and generated potential
      qualitative research applications to emergency medicine research. We have added a
      methodological contribution to the ongoing debate about rigour in qualitative
      research which we hope will guide future studies in this topic in emergency care
      research. It also provided recommendations for conducting future mixed-methods
      studies. Future papers on this series will use the results from qualitative data
      and the empirical findings from longitudinal data linkage to further identify
      factors associated with ED performance; they will be reported separately.

PMID- 29454351
TI  - Disparate compensation policies for research related injury in an era of
      multinational trials: a case study of Brazil, Russia, India, China and South
      Africa.
AB  - BACKGROUND: Compensation for research related injuries is a subject that is
      increasingly gaining traction in developing countries which are burgeoning
      destinations of multi center research. However, the existence of disparate
      compensation rules violates the ethical principle of fairness. The current paper
      presents a comparison of the policies of Brazil, Russia, India, China and South
      Africa (BRICS). METHODS: A systematic search of good clinical practice guidelines
      was conducted employing search strategies modeled in line with the
      recommendations of ADPTE Collaboration (2007). The search focused on three main
      areas namely bibliographic data bases, clinical practice guidelines data bases
      and a restricted internet search. A manual search of references cited in relevant
      guideline documents was also conducted. The search terms, Medical Subject
      Headings (MeSH) and key words were developed for a PubMed platform and then
      adapted for all other data bases. The search terms were kept constant for each
      country with the only difference being the country name. The documents so
      obtained were subjected to systematic content analysis. RESULTS: The study
      revealed that there is vast panoply of regulations which exist on a continuum. On
      one extreme is India with comprehensive regulations that are codified into law,
      and on the other end there is China which does not have specific laws regulating
      research related injuries. There are a number of differences and similarities
      such as mandatory insurance requirements, existence of no fault compensation,
      compensable injuries and the role of research ethics committees. CONCLUSIONS: It
      is imperative to enact legislations that protect participants without stifling
      the research enterprise. There is need for consistency and ideally harmonization
      of such regulations at a global level. A model policy on compensation for
      research related injuries should borrow from the best aspects of the different
      country policies and should be informed by the cardinal ethics principles of
      autonomy, justice and beneficence.

PMID- 29454352
TI  - Lower pole approach in retroperitoneal laparoscopic radical nephrectomy: a new
      approach for the management of renal vascular pedicle.
AB  - BACKGROUND: The objective of this study was to examine the effectiveness and
      safety of lower pole (LP) approach in retroperitoneal laparoscopic radical
      nephrectomy (LRN). METHODS: One hundred thirty-two renal cancer patients were
      scheduled for selective retroperitoneal LRN. The surgery parameters and outcomes
      were compared. Out of 132 patients, 78 (59.1%) patients underwent LRN via LP
      approach, while 54 (40.9%) patients underwent LRN via lateroposterior space (LPS)
      approach. RESULTS: Compared to LPS group, the LP group had a higher body mass
      index (27.0 +/- 1.7 kg/m2 vs. 24.5 +/- 1.8 kg/m2, P <  0.0001) and a larger tumor
      size (6.9 +/- 3.5 cm vs. 4.1 +/- 3.3 cm, P <  0.0001). The LP approach reduced
      the volumes of blood loss and transfusion significantly (135.3 +/- 17.2 mL vs.
      219.6 +/- 30.9 mL, P <  0.0001; 55.6 +/- 28.3 vs. 141.1 +/- 50.4 mL, P <  0.0001)
      as compared to the LPS approach. The LP approach also decreased the risk of
      conversion to open procedure (1.3 vs. 7.4%, P <  0.05). CONCLUSIONS: The LP
      approach is an effective and safe alternative to the LPS approach for
      retroperitoneal LRN and might be more suitable for patients with obesity, large
      tumors, tumors located at the medial part of the kidney, or renal pedicular
      adhesion.

PMID- 29454354
TI  - Cerebrospinal fluid level of Nogo receptor 1 antagonist lateral olfactory tract
      usher substance (LOTUS) correlates inversely with the extent of
      neuroinflammation.
AB  - BACKGROUND: Although inflammation in the central nervous system is responsible
      for multiple neurological diseases, the lack of appropriate biomarkers makes it
      difficult to evaluate inflammatory activities in these diseases. Therefore, a new
      biomarker reflecting neuroinflammation is required for accurate diagnosis,
      appropriate therapy, and comprehension of pathogenesis of these neurological
      disorders. We previously reported that the cerebrospinal fluid (CSF)
      concentration of lateral olfactory tract usher substance (LOTUS), which promotes
      axonal growth as a Nogo receptor 1 antagonist, negatively correlates with disease
      activity in multiple sclerosis, suggesting that variation in LOTUS reflects the
      inflammatory activities and is a useful biomarker to evaluate the disease
      activity. To extend this observation, we analyzed the variation of LOTUS in the
      CSF of patients with bacterial and viral meningitis, which are the most common
      neuroinflammatory diseases. METHODS: CSF samples were retrospectively obtained
      from patients with meningitis (n = 40), who were followed up by CSF study at
      least twice, and from healthy controls (n = 27). Patients were divided into
      bacterial (n = 14) and viral meningitis (n = 18) after exclusion of eight
      patients according to the criteria of this study. LOTUS concentrations, total
      protein levels, and CSF cell counts in the acute and recovery phases were
      analyzed chronologically. We also used lipopolysaccharide-injected mice as a
      model of neuroinflammation to evaluate LOTUS mRNA and protein expression in the
      brain. RESULTS: Regardless of whether meningitis was viral or bacterial, LOTUS
      concentrations in the CSF of patients in acute phase were lower than those of
      healthy controls. As the patients recovered from meningitis, LOTUS levels in the
      CSF returned to the normal range. Lipopolysaccharide-injected mice also exhibited
      reduced LOTUS mRNA and protein expression in the brain. CONCLUSIONS: CSF levels
      of LOTUS correlated inversely with disease activity in both bacterial and viral
      meningitis, as well as in multiple sclerosis, because neuroinflammation
      downregulated LOTUS expression. Our data strongly suggest that variation of CSF
      LOTUS is associated with neuroinflammation and is useful as a biomarker for a
      broader range of neuroinflammatory diseases.

PMID- 29454355
TI  - Temporal changes of fine root overyielding and foraging strategies in planted
      monoculture and mixed forests.
AB  - BACKGROUND: Mixed forests are believed to enhance ecosystem functioning and
      sustainability due to complementary resource use, environmental benefits and
      improved soil properties. The facilitation between different species may induce
      overyielding. Meanwhile, the species-specific fine root foraging strategies and
      tradeoffs would determine the structure and dynamics of plant communities. Here
      the aim was to investigate the admixing effects of fine-root biomass, vertical
      distribution and morphology in Pinus massoniana-Cinnamomum camphora mixed
      plantations and corresponding monocultures at 10-, 24- and 45-year old stands.
      RESULTS: The fine root biomass in the Pinus-Cinnamomum mixed forest exerted a
      certain degree of overyielding effect. These positive admixing effects, however,
      did not enhance with forest stand development. The overall relative yield total
      ranged from 1.83 and 1.51 to 1.33 in 10-, 24- and 45-year-old stand,
      respectively. The overyielding was mainly attributed to the over-performance of
      late successional species, Cinnamomum, in mixed stands. The vertical fine root
      biomass distribution model showed fine roots of pioneer species, Pinus, shifted
      to the superficial layer when mixed with Cinnamomum. Furthermore, the specific
      root length (SRL) of Pinus was significantly higher in Pinus-Cinnamomum mixed
      stands than that in monocultures, and the magnitude of differences increased over
      time. However, the vertical fine-root distribution and SRL for Cinnamomum did not
      show significant differences between monoculture and mixtures. CONCLUSIONS: Our
      results indicated that the magnitude of fine root overyielding in mixed forests
      showed a high degree of consistency with the total amount of fine root biomass
      itself, suggesting the overyielding effects in mixed forests were correlated with
      the degree of belowground interaction and competition degree involved. The late
      successional species, Cinnamomum, invested more carbon to belowground by
      increasing the fine root biomass in mixtures. While the pioneer species, Pinus,
      adapted to the presence of the species Cinnamomum by modification of vertical
      distribution and root morphological plasticity in the mixtures. These species
      specific fine root foraging strategies might imply the differences of forest
      growth strategies of co-occurring species and contribute to the success and
      failure of particular species during the succession over time.

PMID- 29454353
TI  - Genetics of the human Y chromosome and its association with male infertility.
AB  - The human Y chromosome harbors genes that are responsible for testis development
      and also for initiation and maintenance of spermatogenesis in adulthood. The long
      arm of the Y chromosome (Yq) contains many ampliconic and palindromic sequences
      making it predisposed to self-recombination during spermatogenesis and hence
      susceptible to intra-chromosomal deletions. Such deletions lead to copy number
      variation in genes of the Y chromosome resulting in male infertility. Three
      common Yq deletions that recur in infertile males are termed as AZF (Azoospermia
      Factor) microdeletions viz. AZFa, AZFb and AZFc. As estimated from data of nearly
      40,000 Y chromosomes, the global prevalence of Yq microdeletions is 7.5% in
      infertile males; however the European infertile men are less susceptible to Yq
      microdeletions, the highest prevalence is in Americans and East Asian infertile
      men. In addition, partial deletions of the AZFc locus have been associated with
      infertility but the effect seems to be ethnicity dependent. Analysis of > 17,000
      Y chromosomes from fertile and infertile men has revealed an association of gr/gr
      deletion with male infertility in Caucasians and Mongolian men, while the b2/b3
      deletion is associated with male infertility in African and Dravidian men.
      Clinically, the screening for Yq microdeletions would aid the clinician in
      determining the cause of male infertility and decide a rational management
      strategy for the patient. As these deletions are transmitted to 100% of male
      offspring born through assisted reproduction, testing of Yq deletions will allow
      the couples to make an informed choice regarding the perpetuation of male
      infertility in future generations. With the emerging data on association of Yq
      deletions with testicular cancers and neuropsychiatric conditions long term
      follow-up data is urgently needed for infertile men harboring Yq deletions. If
      found so, the information will change the current the perspective of
      androgenetics from infertility and might have broad implication in men health.

PMID- 29454356
TI  - Multiple forms of discrimination and relationships with health and wellbeing:
      findings from national cross-sectional surveys in Aotearoa/New Zealand.
AB  - BACKGROUND: The complex ways in which experiences of discrimination are patterned
      in society, including the exposure of communities to multiple overlapping forms
      of discrimination within social systems of oppression, is increasingly recognised
      in the health sciences. However, research examining the impacts on health and
      contribution to racial/ethnic health inequities remains limited. This study aims
      to contribute to the field by exploring the prevalence and patterning of
      experience of multiple forms of discrimination in Aotearoa/New Zealand, and
      associations with health and wellbeing. METHODS: The study's conceptual approach
      is informed by Kaupapa Maori theory, Ecosocial theory, Critical Race Theory and
      intersectionality. Data are from the 2008, 2010 and 2012 General Social Surveys
      (GSS), biennial nationally-representative surveys in Aotearoa/New Zealand. We
      examined patterning of forms of discrimination in the last 12 months and
      frequency of experiencing multiple forms of discrimination. We also looked at
      associations between experience of multiple discrimination and self-rated health,
      mental health (using SF12), and life satisfaction using logistic regression. We
      used random effects meta-analysis to produce pooled estimates drawing from all
      three survey instances. RESULTS: Maori, and people from Pacific and Asian ethnic
      groups, reported much higher prevalence of racial discrimination, were more
      likely to have any experience of discrimination, and were also more likely to
      experience multiple forms of discrimination, in the last year relative to
      respondents in the European/Other category. Discrimination was associated with
      poorer self-rated health, poorer mental health, and greater life dissatisfaction
      in unadjusted and adjusted estimates. Negative health impacts increased as the
      number of forms of discrimination experienced increased. CONCLUSIONS:
      Discrimination impacts negatively on the health of indigenous peoples and those
      from minoritised ethnic groups in Aotearoa/New Zealand through higher exposure to
      racial discrimination, other forms of discrimination, and a greater likelihood of
      experiencing multiple forms of discrimination. This supports the need for
      research and interventions that more fully account for the multiple and
      interlocking ways in which discrimination impacts on health in racialised social
      hierarchies to maintain systems of privilege and oppression.

PMID- 29454357
TI  - Border analysis for spatial clusters.
AB  - BACKGROUND: The spatial scan statistic is widely used by public health
      professionals in the detection of spatial clusters in inhomogeneous point
      process. The most popular version of the spatial scan statistic uses a circular
      shaped scanning window. Several other variants, using other parametric or non
      parametric shapes, are also available. However, none of them offer information
      about the uncertainty on the borders of the detected clusters. METHOD: We propose
      a new method to evaluate uncertainty on the boundaries of spatial clusters
      identified through the spatial scan statistic for Poisson data. For each spatial
      data location i, a function F(i) is calculated. While not a probability, this
      function takes values in the [0, 1] interval, with a higher value indicating more
      evidence that the location belongs to the true cluster. RESULTS: Through a set of
      simulation studies, we show that the F function provides a way to define, measure
      and visualize the certainty or uncertainty of each specific location belonging to
      the true cluster. The method can be applied whether there are one or multiple
      detected clusters on the map. We illustrate the new method on a data set
      concerning Chagas disease in Minas Gerais, Brazil. CONCLUSIONS: The higher the
      intensity given to an area, the higher the plausibility of that particular area
      to belong to the true cluster in case it exists. This way, the F function
      provides information from which the public health practitioner can perform a
      border analysis of the detected spatial scan statistic clusters. We have
      implemented and illustrated the border analysis F function in the context of the
      circular spatial scan statistic for spatially aggregated Poisson data. The
      definition is clearly independent of both the shape of the scanning window and
      the probability model under which the data is generated. To make the new method
      widely available to users, it has been implemented in the freely available
      SaTScan[Formula: see text] software www.satscan.org .

PMID- 29454358
TI  - Surgical resection for clinical stage I high-grade neuroendocrine carcinoma of
      the lung.
AB  - BACKGROUND: There are few reports about the factor influencing the prognosis of
      high-grade neuroendocrine carcinoma. In this study, we evaluated surgical outcome
      of clinical stage I high-grade neuroendocrine carcinoma. METHODS: Patients who
      underwent curative surgery for high-grade neuroendocrine tumors of the lung in
      clinical stage I were included in this study. We retrospectively analyzed 27
      consecutive patients. The aim of this study was to clarify the clinical course of
      the disease after surgery and what factors influence the prognosis. RESULTS:
      Twenty-two patients have small cell carcinoma, and 5 patients have large cell
      neuroendocrine carcinoma. Patients who could undergo surgery within 60 days after
      the first visit (p < 0.01) and undergo lobectomy (p < 0.01) and whose pro-gastrin
      releasing peptide ? 72 pg/ml (p = 0.04) performed good prognosis after surgery.
      In multivariate analysis, surgery within 60 days and operative procedure were
      independent factors associated with OS. CONCLUSION: Surgical resection for
      clinical stage I high-grade neuroendocrine carcinoma of the lung should be
      performed as early as possible, and better outcome can be obtained with lobectomy
      than partial resection.

PMID- 29454359
TI  - Change in practice: a qualitative exploration of midwives' and doctors' views
      about the introduction of STan monitoring in an Australian hospital.
AB  - BACKGROUND: The present study examines the introduction of an innovation in
      intrapartum foetal monitoring practice in Australia. ST-Analysis (STan) is a
      technology that adds information to conventional fetal monitoring
      (cardiotocography) during labour, with the aim of reducing unnecessary obstetric
      intervention. Adoption of this technology has been controversial amongst
      obstetricians and midwives, particularly as its use necessitates a more invasive
      means of monitoring (a scalp clip), compared to external monitoring from
      cardiotocography alone. If adoption of this technology is going to be successful,
      then understanding staff opinions about the implementation of STan in an
      Australian setting is an important issue for maternity care providers and policy
      makers. METHODS: Using a maximum variation purposive sampling method, 18
      interviews were conducted with 10 midwives and 8 doctors from the Women's and
      Children's Hospital, South Australia to explore views about the introduction of
      the new technology. The data were analysed using Framework Analysis. RESULTS:
      Midwives and doctors indicated four important areas of consideration when
      introducing STan: 1) philosophy of care; 2) the implementation process including
      training and education; 3) the existence of research evidence; and 4) attitudes
      towards the new technology. Views were expressed about the management of change
      process, the fit of the new technology within the current models of care, the
      need for ongoing training and the importance of having local evidence.
      CONCLUSIONS: These findings, coupled with the general literature about
      introducing innovation and change, can be used by other centres looking to
      introduce STan technology.

PMID- 29454360
TI  - Reliability of length measurements collected by community nurses and health
      volunteers in rural growth monitoring and promotion services.
AB  - BACKGROUND: Length measurements are important in growth, monitoring and promotion
      (GMP) for the surveillance of a child's weight-for-length and length-for-age.
      These two indices provide an indication of a child's risk of becoming wasted or
      stunted, and are more informative about a child's growth than the widely used
      weight-for-age index (underweight). Although the introduction of length
      measurements in GMP is recommended by the World Health Organization, concerns
      about the reliability of length measurements collected in rural outreach settings
      have been expressed by stakeholders. Our aim was to describe the reliability and
      challenges associated with community health personnel measuring length for rural
      outreach GMP activities. METHODS: Two reliability studies (A and B), using 10
      children less than 24 months each, were conducted in the GMP services of a rural
      district in Ghana. Fifteen nurses and 15 health volunteers (HV) with no prior
      experience in length measurements were trained. Intra- and inter-observer
      technical error of measurement (TEM), average bias from expert anthropometrist,
      and coefficient of reliability (R) of length measurements were assessed and
      compared across sessions. Observations and interviews were used to understand the
      ability and experiences of health personnel with measuring length at outreach
      GMP. RESULTS: Inter-observer TEM was larger than intra-observer TEM for both
      nurses and HV at both sessions and was unacceptably (compared to error standards)
      high in both groups at both time points. Average biases from expert's
      measurements were within acceptable limits, however, both groups tended to
      underestimate length measurements. The R for lengths collected by nurses (92.3%)
      was higher at session B compared to that of HV (87.5%). Length measurements taken
      by nurses and HV, and those taken by an experienced anthropometrist at GMP
      sessions were of moderate agreement (kappa = 0.53, p < 0.0001). CONCLUSIONS: The
      reliability of length measurements improved after two refresher trainings for
      nurses but not for HV. In addition, length measurements taken during GMP sessions
      may be susceptible to errors due to overburdened health personnel and crowded GMP
      clinics. There is need for both pre- and in-service training of nurses and HV on
      length measurements and procedures to improve reliability of length measurements.

PMID- 29454361
TI  - Wnt-signaling enhances neural crest migration of melanoma cells and induces an
      invasive phenotype.
AB  - BACKGROUND: During embryonic development Wnt family members and bone
      morphogenetic proteins (BMPs) cooperatively induce epithelial-mesenchymal
      transition (EMT) in the neural crest. Wnt and BMPs are reactivated during
      malignant transformation in melanoma. We previously demonstrated that the BMP
      antagonist noggin blocked the EMT phenotype of melanoma cells in the neural crest
      and malignant invasion of melanoma cells in the chick embryo; vice-versa,
      malignant invasion was induced in human melanocytes in vivo by pre-treatment with
      BMP-2. RESULTS: Although there are conflicting results in the literature about
      the role of beta-catenin for invasion of melanoma cells, we found Wnt/beta
      catenin signaling to be analogously important for the EMT-like phenotype of human
      metastatic melanoma cells in the neural crest and during invasion: beta-catenin
      was frequently expressed at the invasive front of human primary melanomas and
      Wnt3a expression was inversely correlated with survival of melanoma patients.
      Accordingly, cytoplasmic beta-catenin levels were increased during invasion of
      melanoma cells in the rhombencephalon of the chick embryo. Fibroblast derived
      Wnt3a reduced melanoma cell adhesion and enhanced migration, while the beta
      catenin inhibitor PKF115-584 increased adhesion and reduced migration in vitro
      and in the chick embryonic neural crest environment in vivo. Similarly, knockdown
      of beta-catenin impaired intradermal melanoma cell invasion and PKF115-584
      efficiently reduced liver metastasis in a chick chorioallantoic membrane model.
      Our observations were accompanied by specific alterations in gene expression
      which are linked to overall survival of melanoma patients. CONCLUSION: We present
      a novel role for Wnt-signaling in neural crest like melanoma cell invasion and
      metastasis, stressing the crucial role of embryonic EMT-inducing neural crest
      signaling for the spreading of malignant melanoma.

PMID- 29454362
TI  - Self-assembly/disassembly hysteresis of nanoparticles composed of marginally
      soluble, short elastin-like polypeptides.
AB  - BACKGROUND: Elastin-like polypeptides (ELPs) are a fascinating biomaterial that
      has undergone copious development for a variety of therapeutic applications
      including as a nanoscale drug delivery vehicle. A comprehensive understanding of
      ELP self-assembly is lacking and this knowledge gap impedes the advancement of
      ELP-based biomaterials into the clinical realm. The systematic examination of
      leucine-containing ELPs endeavors to expand existing knowledge about fundamental
      assembly-disassembly behaviours. RESULTS: It was observed that these marginally
      soluble, short ELPs tend to behave consistently with previous observations
      related to assembly-related ELP phase transitions but deviated in their
      disassembly. It was found that chain length, concentration and overall sequence
      hydrophobicity may influence the irreversible formation of sub-micron particles
      as well as the formation of multi-micron scale, colloidally unstable aggregates.
      Amino acid composition affected surface charge and packing density of the
      particles. Particle stability upon dilution was found to vary depending upon
      chain length and hydrophobicity, with particles composed of longer and/or more
      hydrophobic ELPs being more resistant to disassembly upon isothermal dilution.
      CONCLUSIONS: Taken together, these results suggest marginally soluble ELPs may
      self-assemble but not disassemble as expected and that parameters including
      particle size, zeta potential and dilution resistance would benefit from
      widespread systematic evaluations. This information has the potential to reveal
      novel preparation methods capable of expanding the utility of all existing ELP
      based biomaterials.

PMID- 29454364
TI  - Cyclosporine A does not prevent second-eye involvement in Leber's hereditary
      optic neuropathy.
AB  - BACKRGROUND: Evaluation of the efficacy of oral cyclosporine A as a prophylactic
      agent in preventing second-eye involvement in Leber's hereditary optic neuropathy
      (LHON) in a prospective, open-label, non-randomized, multicenter pilot study.
      Only LHON patients aged 18 years or more, with confirmed primary mitochondrial
      DNA mutations and strictly unilateral optic neuropathy occurring within 6 months
      prior to enrolment, were included in the study. All these patients, receiving
      treatment with oral cyclosporine (Neoral(r), Novartis) at 2.5 mg/kg/day, were
      examined at three-month intervals for a year. The primary endpoint was the best
      corrected visual acuity in the unaffected eye; the secondary endpoints were the
      best corrected visual acuity in the first eye affected, the mean visual field
      defect on automated perimetry, the thickness of the perifoveal retinal ganglion
      cell inner plexiform layer, and the thickness of the peripapillary retinal nerve
      fiber layer in both eyes. RESULTS: Among the 24 patients referred to our
      institution with genetically confirmed LHON, between July 2011 and April 2014,
      only five patients, four males and one female, fulfilled the inclusion criteria.
      Age at enrolment ranged from 19 to 42 years (mean: 27.2 years; median: 26 years),
      four patients harbored the m.11778G > A pathogenic variant, and one the m.14484 T
      > C pathogenic variant. The time-interval between the onset of symptoms and
      inclusion in the study ranged from 7 to 17 weeks (mean: 11.8 weeks; median: 9
      weeks). Despite treatment with oral cyclosporine A, all patients eventually
      experienced bilateral eye involvement, occurring within 11-65 weeks after the
      initiation of treatment. Over the study time period, the average best corrected
      visual acuity worsened in the first eye affected; by the end of the study, both
      eyes were equally affected. CONCLUSIONS: Oral cyclosporine, at 2.5 mg/kg/day, did
      not prevent second-eye involvement in patients with strictly unilateral Leber's
      hereditary optic neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT02176733 . Registrated June 25, 2014.

PMID- 29454365
TI  - Qualitative evaluation of the Saleema campaign to eliminate female genital
      mutilation and cutting in Sudan.
AB  - BACKGROUND: Female genital mutilation and cutting (FGM/C, herein FGM) is a
      widespread and harmful practice. The Government developed a national campaign in
      Sudan, called Saleema, to change social norms discouraging FGM. Saleema
      translates to being "whole", healthy in body and mind, unharmed, intact,
      pristine, and untouched, in a God-given condition. An interim evaluation was
      conducted using focus groups among Sudanese adults. The primary aim was to
      explore perceptions of the Saleema poster exemplars and to assess if the desired
      themes were being communicated. Secondary aims were to understand more about
      participants' information sources, values, and suggestions for the campaign
      broadly. METHODS: The Saleema campaign evaluation included four focus groups from
      each of the 18 states in Sudan (72 total). Participants were presented with three
      poster stimuli from the Saleema campaign and asked about the content and their
      reactions. Themes were coded inductively by concepts that arose through content
      in the transcripts. Codes were also reviewed in conjunction with themes from the
      broader Saleema evaluation framework. RESULTS: Participants reported the most
      common source of information or admiration was from local leaders who are
      responsive to a community, media-based outlets, and discussions among community
      members. Participants held high value for education, community solidarity, and/or
      religious devotion. Participants had positive opinions of Saleema and responded
      positively to the branding elements in the posters and the campaign as a whole.
      The most common suggestion was continued awareness. Advocacy, training, and
      posters were suggested to highlight the harms of FGM through leaders or in
      community settings. Individuals suggested that these activities target older
      women and individuals in rural villages. There was also a burgeoning theme of
      targeting youth for support of the campaign. DISCUSSION: The results of this
      focus group analysis demonstrate support for future Saleema campaign efforts
      promoting awareness and community engagement. The campaign could capitalize on
      partnerships with young people and those who are respected in the community
      (e.g., religious leaders) or continue promoting common values aligning with the
      support of education and community solidarity. Continuing campaign efforts have
      promise to decrease the harms of FGM in Sudan.

PMID- 29454363
TI  - Identification of wild-caught phlebotomine sand flies from Crete and Cyprus using
      DNA barcoding.
AB  - BACKGROUND: Phlebotomine sand flies (Diptera: Psychodidae) are vectors of
      Leishmania spp., protozoan parasites responsible for a group of neglected
      diseases called leishmaniases. Two sand fly genera, Phlebotomus and Sergentomyia,
      contain species that are present in the Mediterranean islands of Crete and Cyprus
      where the visceral (VL), cutaneous (CL) and canine (CanLei) leishmaniases are a
      public health concern. The risk of transmission of different Leishmania species
      can be studied in an area by monitoring their vectors. Sand fly species are
      traditionally identified using morphological characteristics but minute
      differences between individuals or populations could be overlooked leading to
      wrong epidemiological predictions. Molecular identification of these important
      vectors has become, therefore, an essential tool for research tasks concerning
      their geographical distribution which directly relates to leishmaniasis control
      efforts. DNA barcoding is a widely used molecular identification method for
      cataloguing animal species by sequencing a fragment of the mitochondrial gene
      encoding cytochrome oxidase I. RESULTS: DNA barcoding was used to identify
      individuals of five sand fly species (Phlebotomus papatasi, P. similis, P.
      killicki, Sergentomyia minuta, S. dentata) circulating in the islands of Crete
      and Cyprus during the years 2011-2014. Phlebotomus papatasi is a known vector of
      zoonotic CL in the Middle East and it is found in both islands. Phlebotomus
      similis is the suspected vector of Leishmania tropica in Greece causing
      anthroponotic CL. Phlebotomus killicki was collected in Cyprus for the first
      time. Sergentomyia minuta, found to present intraspecific diversity, is discussed
      for its potential as a Leishmania vector. Molecular identification was consistent
      with the morphological identification. It successfully identified males and
      females, which is difficult when using only morphological characters. A
      phylogenetic tree was constructed based on the barcodes acquired, representing
      their genetic relationships along with other species from the area studied. All
      individuals identified were clustered according to their species and subgenus.
      CONCLUSIONS: Molecular identification of sand flies via DNA barcoding can
      accurately identify these medically important insects assisting traditional
      morphological tools, thus helping to assess their implication in Leishmania
      transmission.

PMID- 29454366
TI  - Occurrence of Blastocystis sp. and Pentatrichomonas hominis in sheep and goats in
      China.
AB  - BACKGROUND: Global data regarding the molecular epidemiology of Blastocystis sp.
      and Pentatrichomonas hominis in sheep and goats are sparse. China has one of the
      largest sheep and goat populations in the world. In this study we investigated
      the occurrence of Blastocystis sp. and P. hominis in domestic sheep and goats in
      China, and analyzed the genetic characterization of these two parasite species.
      METHODS: In total, we collected fresh fecal samples from 832 sheep and 781 goats
      located on seven and ten farms, respectively, in the central eastern region of
      China. The corresponding sequences obtained in this study were subject to
      molecular analysis for subtype and allele identification of Blastocystis sp., and
      species and genotype confirmation of P. hominis. RESULTS: The occurrence of
      Blastocystis sp. was 6.0% (50/832) in sheep and 0.3% (2/781) in goats. The most
      predominant subtype (ST) of Blastocystis sp. in sheep was ST10 (50.0%), followed
      by ST14 (20%), ST5 (16%), novel sequence 1 (6%), novel sequence 4 (4%), novel
      sequence 2 (2%) and novel sequence 3 (2%). However, only ST1 was observed in
      goats. No mixed infections with different subtypes were found in this study. The
      18S alleles showed allele 2 (100%) for ST1; allele 115 (75%) for ST5; and no
      match allele for ST5 (25%), ST10 (100%), ST14 (100%), novel sequence 1 (100%),
      novel sequence 2 (100%), novel sequence 3 (100%), and novel sequence 4 (100%) on
      the Blastocystis subtype (18S) and Sequence Typing (MLST) database. For P.
      hominis, two goats (0.3%) and zero sheep (0%) were identified as positive in this
      study. The 18S rRNA gene sequences of two P. hominis isolates from goats
      displayed 100% identity to type CC1, found previously in dogs, monkeys and
      humans. CONCLUSIONS: These results provide the detailed data on the occurrence
      and molecular epidemiology of Blastocystis sp. and P. hominis in sheep and goats
      in China. They also contribute to and expand our knowledge of the Blastocystis
      sp. and P. hominis epidemiology around the world.

PMID- 29454367
TI  - Reassessment of the capacity of the HIV-1 Env cytoplasmic domain to trigger NF
      kappaB activation.
AB  - The cytoplasmic domain of lentiviral Envelopes (EnvCD) ensures Env incorporation
      into nascent virions and regulates Env trafficking to and from the plasma
      membrane. It has also been reported to promote transcription from the viral LTR
      both directly and indirectly. Noticeably, the HIV-1 and SIVmac239 EnvCDs were
      described to trigger nuclear translocation of NF-kappaB (Postler, Cell Host
      Microbes 2012). Given the paramount importance of identifying viral and host
      factors regulating HIV transcription, cellular signaling pathways and latency,
      and given that viral replication capacity is dependent on Env, we asked whether
      HIV EnvCDs from different HIV-1 subtypes differently modulated NF-kappaB. To that
      aim, we evaluated the ability of primary HIV-1 Envs from subtypes B and C to
      activate the NF-kappaB pathway. Primary subtype B and C Envs all failed to
      activate the NF-kappaB pathway. In contrast, when the EnvCD of HIV-1 Envs was
      fused to the the CD8-alpha chain, it induced ~ 10-fold increase in NF-kappaB
      induction, and this increase was much stronger with a truncated form of the HIV
      EnvCD lacking the 76 C-terminal residues and containing the proposed TAK-1
      binding domain. Our results indicate that the HIV-1 EnvCD is unlikely to trigger
      the NF-kappaB pathway in its native trimeric form.

PMID- 29454368
TI  - Survey indicated that core outcome set development is increasingly including
      patients, being conducted internationally and using Delphi surveys.
AB  - BACKGROUND: There are numerous challenges in including patients in a core outcome
      set (COS) study, these can vary depending on the patient group. This study
      describes current efforts to include patients in the development of COS, with the
      aim of identifying areas for further improvement and study. METHODS: Using the
      COMET database, corresponding authors of COS projects registered or published
      from 1 January 2013 to 2 February 2017 were invited via a personalised email to
      participate in a short online survey. The survey and emails were constructed to
      maximise the response rate by following the academic literature on enhancing
      survey responses. Personalised reminder emails were sent to non-responders. This
      survey explored the frequency of patient input in COS studies, who was involved,
      what methods were used and whether or not the COS development was international.
      RESULTS: One hundred and ninety-two COS developers were sent the survey.
      Responses were collected from 21 February 2017 until 7 May 2017. One hundred and
      forty-six unique developers responded, yielding a 76% response rate and data in
      relation to 195 unique COSs (as some developers had worked on multiple COSs). Of
      focus here are their responses regarding 162 COSs at the published, completed or
      ongoing stages of development. Inclusion of patient participants was indicated in
      87% (141/162) of COSs in the published completed or ongoing stages and over 94%
      (65/69) of ongoing COS projects. Nearly half (65/135) of COSs included patient
      participants from two or more countries and 22% (30/135) included patient
      participants from five or more countries. The Delphi survey was reported as being
      used singularly or in combination with other methods in 85% (119/140) of
      projects. Almost a quarter (16/65) of ongoing studies reported using a
      combination of qualitative interviews, Delphi survey and consensus meeting.
      CONCLUSIONS: These findings indicated that the Delphi survey is the most popular
      method of facilitating patient participation, while the combination of
      qualitative interviews, Delphi survey and consensus meetings is the most popular
      combination of methods. The increased inclusion of patient participants in the
      development of COSs is encouraging, as is the international approach to COS
      development that some developers are adopting.

PMID- 29454369
TI  - Evaluation of piezocision and laser-assisted flapless corticotomy in the
      acceleration of canine retraction: a randomized controlled trial.
AB  - BACKGROUND: To evaluate the effectiveness of two minimally invasive surgical
      procedures in the acceleration of canine retraction: piezocision and laser
      assisted flapless corticotomy (LAFC). METHODS: Trial design: A single-centre
      randomized controlled trial with a compound design (two-arm parallel-group design
      and a split-mouth design for each arm). PARTICIPANTS: 36 Class II division I
      patients (12 males, 24 females; age range: 15 to 27 years) requiring first upper
      premolars extraction followed by canine retraction. INTERVENTIONS: piezocision
      group (PG; n = 18) and laser-assisted flapless corticotomy group (LG; n = 18). A
      split-mouth design was applied for each group where the flapless surgical
      intervention was randomly allocated to one side and the other side served as a
      control side. OUTCOMES: the rate of canine retraction (primary outcome),
      anchorage loss and canine rotation, which were assessed at 1, 2, 3 and 4 months
      following the onset of canine retraction. Also the duration of canine retraction
      was recorded. Random sequence: Computer-generated random numbers. Allocation
      concealment: sequentially numbered, opaque, sealed envelopes. Blinding: Single
      blinded (outcomes' assessor). RESULTS: Seventeen patients in each group were
      enrolled in the statistical analysis. The rate of canine retraction was
      significantly greater in the experimental side than in the control side in both
      groups by two-fold in the first month and 1.5-fold in the second month (p <
      0.001). Also the overall canine retraction duration was significantly reduced in
      the experimental side as compared with control side in both groups about 25% (p
      <= 0.001). There were no significant differences between the experimental and the
      control sides regarding loss of anchorage and upper canine rotation in both
      groups (p > 0.05). There were no significant differences between the two flapless
      techniques regarding the studied variables during all evaluation times (p >
      0.05). CONCLUSIONS: Piezocision and laser-assisted flapless corticotomy appeared
      to be effective treatment methods for accelerating canine retraction without any
      significant untoward effect on anchorage or canine rotation during rapid
      retraction. TRIALS REGISTRATION: ClinicalTrials.gov (Identifier: NCT02606331 ).

PMID- 29454370
TI  - Isolation of a novel Rhabdovirus from an insectivorous bat (Pipistrellus kuhlii)
      in Italy.
AB  - BACKGROUND: Rhabdoviridae is one of the most ecologically diverse families of RNA
      viruses which can infect a wide range of vertebrates and invertebrates. Bats,
      among mammals, are pointed to harbor a significantly higher proportion of unknown
      or emerging viruses with zoonotic potential. Herein, we report the isolation of a
      novel rhabdovirus, detected in the framework of a virological survey on bats
      implemented in North Italy. METHODS: Virus isolation and identification were
      performed on samples of 635 bats by using cell cultures, negative staining
      electron microscopy and PCRs for different viruses. NGS was commonly performed on
      cell culture supernatants showing cytopathic effect or in case of samples
      resulted positive by at least one of the PCRs included in the diagnostic
      protocol. RESULTS: A rhabdovirus was isolated from different organs of a
      Pipistrellus kuhlii. Virus identification was obtained by electron microscopy and
      NGS sequencing. The complete genome size was 11,774 nt comprised 5 genes,
      encoding the canonical rhabdovirus structural proteins, and an additional
      transcriptional unit (U1) encoding a hypothetical small protein (157aa) (3'-N-P-M
      G-U1-L-5'). The genome organization and phylogenetic analysis suggest that the
      new virus, named Vaprio virus (VAPV), belongs to the recently established genus
      Ledantevirus (subgroup B) and it is highly divergent to its closest known
      relative, Le Dantec virus (LDV) (human, 1965 Senegal). A specific RT-PCR
      amplifying a 350 bp fragment of the ORF 6 gene, encoding for L protein, was
      developed and used to test retrospectively a subset of 76 bats coming from the
      same area and period, revealing two more VAPV positive bats. CONCLUSIONS: VAPV is
      a novel isolate of chiropteran rhabdovirus. Genome organization and phylogenetic
      analyses demonstrated that VAPV should be considered a novel species within the
      genus Ledantevirus for which viral ecology and disease associations should be
      investigated.

PMID- 29454371
TI  - Auditory effects of autologous fat graft for TORP stabilization in the middle
      ear: a cadaveric study.
AB  - BACKGROUND: Total ossicular replacement prostheses (TORP) are often used to re
      establish ossicular coupling of sound in an ear lacking a stapes supra-structure.
      The use of TORPs, however, is associated with a 2/3 five year failure rate due to
      their anatomic instability over time in the middle ear. The use of autologous fat
      to try and stabilize TORPs may improve long-term results with this challenging
      ossicular reconstruction technique. METHODS: A cadaveric temporal bone model was
      developed and laser Doppler vibrometry was used to measure and record round
      window membrane vibration in response to sound stimulation under the following
      conditions: normal middle ear, middle ear filled with fat, normal middle ear with
      TORP prosthesis, TORP prosthesis with fat around its distal end and TORP
      prosthesis with fat filling the middle ear. Fourteen temporal bones were used.
      RESULTS: There was a significant decrease in round window membrane velocity after
      filling the middle ear with fat in both the normal middle ear (- 8.6 dB; p <
      0.0001) and prosthesis conditions (- 13.7 dB; p < 0.0001). However, there was no
      significant drop in round window membrane velocity associated with using fat
      around the distal end of the TORP prosthesis as compared to the prosthesis
      without fat condition (p > 0.05). CONCLUSIONS: Autologous fat around the distal
      end of a TORP prosthesis may not be associated with any additional hearing loss,
      as demonstrated in this cadaveric model. The additional hearing loss potentially
      caused by using fat to completely surround the prosthesis and fill the middle ear
      is probably not clinically acceptable at this time, especially given the unknown
      way in which the fat will atrophy over time in this context.

PMID- 29454372
TI  - A novel combination of bortezomib, lenalidomide, and clarithromycin produced
      stringent complete response in refractory multiple myeloma complicated with
      diabetes mellitus - clinical significance and possible mechanisms: a case report.
AB  - BACKGROUND: In general, dexamethasone is a required component drug in various
      combination chemotherapies for treating multiple myeloma, and its efficacy has
      been widely recognized. However, administration of dexamethasone is known to
      cause various adverse effects including hyperglycemia which requires insulin
      therapy. During the course of treatment, we developed a novel effective
      dexamethasone-free combination regimen and evaluated it for its effect in
      multiple myeloma. CASE PRESENTATION: We report a case of 68-year-old Japanese
      woman with refractory advanced Bence-Jones-lambda type multiple myeloma
      associated with diabetes mellitus. Various combination regimens were carried out,
      but the response to some regimens was insufficient or others containing
      dexamethasone, although effective, were inappropriate to continue due to
      aggravation of diabetes mellitus. Thus, we developed a dexamethasone-free, short
      dosing-period regimen consisting of bortezomib, lenalidomide, and clarithromycin.
      This regimen was found to be highly effective and succeeded in achieving
      stringent complete response. CONCLUSIONS: The successful dexamethasone-free
      regimen clearly shows that dexamethasone is not a requisite component in treating
      multiple myeloma, and it can be substituted with clarithromycin. This regimen is
      particularly useful for treating patients with multiple myeloma associated with
      diabetes mellitus.

PMID- 29454373
TI  - Subclinical hypothyroidism in children: is it always subclinical?
AB  - Aim of this commentary is to report current knowledges on the main clinical and
      metabolic abnormalities which might be observed in children with longstanding and
      untreated subclinical hypothyroidism (SH) and to comment the most recent views
      about natural evolution of thyroid function in the cases with either idiopathic
      or Hashimoto's thyroiditis-related SH. On the basis of these preliminary remarks,
      the essential guidelines for an appropriate and tailored management of SH
      children are also proposed.

PMID- 29454374
TI  - Effects of umbilical cord blood cells, and subtypes, to reduce neuroinflammation
      following perinatal hypoxic-ischemic brain injury.
AB  - BACKGROUND: It is well understood that hypoxic-ischemic (HI) brain injury during
      the highly vulnerable perinatal period can lead to cerebral palsy, the most
      prevalent cause of chronic disability in children. Recently, human clinical
      trials have reported safety and some efficacy following treatment of cerebral
      palsy using umbilical cord blood (UCB) cells. UCB is made up of many different
      cell types, including endothelial progenitor cells (EPCs), T regulatory cells
      (Tregs), and monocyte-derived suppressor cells (MDSCs). How each cell type
      contributes individually towards reducing neuroinflammation and/or repairing
      brain injury is not known. In this study, we examined whether human (h) UCB, or
      specific UCB cell types, could reduce peripheral and cerebral inflammation, and
      promote brain repair, when given early after perinatal HI brain injury. METHODS:
      HI brain injury was induced in postnatal day (PND) 7 rat pups and cells were
      administered intraperitoneally on PND 8. Behavioral testing was performed 7 days
      post injury, and then, brains and spleens were collected for analysis. RESULTS:
      We found in vitro that all UCB cell types, except for EPCs, were
      immunomodulatory. Perinatal HI brain injury induced significant infiltration of
      CD4+ T cells into the injured cerebral hemisphere, and this was significantly
      reduced by all hUCB cell types tested. Compared to HI, UCB, Tregs, and EPCs were
      able to reduce motor deficits, reduce CD4+ T cell infiltration into the brain,
      and reduce microglial activation. In addition to the beneficial effects of UCB,
      EPCs also significantly reduced cortical cell death, returned CD4+ T cell
      infiltration to sham levels, and reduced the peripheral Th1-mediated pro
      inflammatory shift. CONCLUSION: This study highlights that cells found in UCB is
      able to mediate neuroinflammation and is an effective neuroprotective therapy.
      Our study also shows that particular cells found in UCB, namely EPCs, may have an
      added advantage over using UCB alone. This work has the potential to progress
      towards tailored UCB therapies for the treatment of perinatal brain injury.

PMID- 29454375
TI  - "Sweeter than a rose", at least to Triatoma phyllosoma complex males
      (Triatominae: Reduviidae).
AB  - BACKGROUND: The Triatoma phyllosoma complex of Trypanosoma cruzi vectors
      (Triatominae: Reduviidae) is distributed in both Neotropical and Nearctic
      bioregions of Mexico. METHODS: Volatile organic compounds emitted by disturbed
      Triatoma longipennis, Triatoma pallidipennis and Triatoma phyllosoma, and from
      their Brindley's and metasternal glands, were identified using solid-phase
      microextraction coupled with gas chromatography-mass spectrometry. RESULTS:
      Disturbed bugs and the metasternal glands from T. phyllosoma released or had
      significantly fewer compounds than T. longipennis and T. pallidipennis.
      Isobutyric acid was the most abundant compound secreted by disturbed bugs of the
      three species, while Brindley's glands of all species produced another four
      compounds: propanoic acid, isobutyric acid, pentyl butanoate, and 2-methyl
      hexanoic acid. Two novel compounds, both rose oxide isomers, were produced in MGs
      and released only by disturbed females of all three species, making this the
      first report in Triatominae of these monoterpenes. The principal compound in MGs
      of both sexes of T. longipennis and T. phyllosoma was 3-methyl-2-hexanone, while
      cis-rose oxide was the principal compound in T. pallidipennis females. The major
      components in male effluvia of T. pallidipennis were 2-decanol and 3-methyl-2
      hexanone. CONCLUSION: Discriminant analysis of volatile organic compounds was
      significant, separating the three species and was consistent with morphological
      and genetic evidence for species distinctions within the complex.

PMID- 29454376
TI  - Seroprevalence of Neospora caninum-specific antibodies in German breeding
      bitches.
AB  - BACKGROUND: Neospora caninum is an intracellular obligate apicomplexan parasite
      responsible for multisystemic lesions in dogs. Being definitive hosts and
      reservoirs, dogs excrete environmentally resistant oocysts. Breeding bitches
      represent a susceptible dog group and infected bitches may spread this parasite
      through transplacental transmission. RESULTS: A total of 218 serum samples of
      German breeding bitches were collected to determine the presence of N. caninum.
      Antibodies were detected in 16 (7.33%) bitches using a commercial indirect enzyme
      linked immunosorbent assay (ELISA). Immunoblotting analysis confirmed all
      seropositive samples detected by ELISA, proving that the animals were infected
      with N. caninum. The owners were interviewed regarding breed, age, environment,
      type, vaccine status, feeding habits and the presence of reproductive disorders.
      Seropositive animals were between the ages of two to seven years; three of them
      were kept in kennels while the others were household dogs, one of which was
      additionally a hunting dog. Owners of four seropositive bitches reported one
      gestation, while multiple pregnancies had been recorded for the other twelve
      bitches. Fourteen bitches were regularly vaccinated and six were fed with fresh
      raw meat. CONCLUSIONS: Although the results confirmed a low incidence of N.
      caninum seropositive German breeding bitches, further epidemiological and
      surveillance studies are required to complement our findings regarding the
      current situation of neosporosis in this specific canine population of Germany.

PMID- 29454377
TI  - Chronic recurrent multifocal osteomyelitis: a case report.
AB  - BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO), also known as
      chronic nonbacterial osteomyelitis, is a rare, noninfectious inflammatory
      disorder that causes multifocal bone lesions with swelling and pain. Lytic and
      sclerotic bone lesions could be found on X-ray. Short tau inversion recovery
      magnetic resonance imaging (STIR MRI) shows bone marrow oedema, bone expansion,
      lytic areas and periosteal reaction. CRMO is characterized by periodic
      exacerbations and remissions of unclear/unknown pathogenesis. CASE PRESENTATION:
      A 10 years old girl, suffering from pain in her right shoulder since the age of 9
      years presented to our Department. Thanks to clinical data, laboratoristic and
      radiological findings and bone biopsy CRMO was diagnosed. So patient started anti
      inflammatory treatment and her conditions improved. CONCLUSIONS: In a child with
      bone pain should be considered also rare condition as CRMO to perform a correct
      diagnosis and start an adequate treatment avoiding complications such as bone
      damage. This condition should be suspected in a child with recurrent bone pain,
      modest increase of inflammatory indices, lytic or sclerotic bone lesion on X Ray.
      Typical CRMO localizations are metaphyses of long bones, pelvis, clavicle,
      vertebral column, sternum, ribs, jaw, but any bone can be involved. The most
      common CRMO differential diagnosis is represented by infections, malignant bone
      tumors, Langerhans Cells Histiocytosis (LCH).

PMID- 29454378
TI  - Do employees benefit from collaborations between out of hours general
      practitioners and emergency departments?
AB  - BACKGROUND: In an attempt to redirect patients who are inappropriately attending
      hospital emergency departments (ED) and in doing so provide the right care at the
      right place, out-of-hours GP (General Practitioner) services and EDs increasingly
      collaborate in Urgent Care Collaborations (UCCs). Work satisfaction is an
      important factor in analysing the impact of this organisational change. The
      objective of this study is, firstly, to discover if there is a difference in the
      employee experiences between those working in UCCs and those in traditional out
      of-hours services in which EDs and out-of-hours GP services operate separately
      (i.e. "usual care"). Secondly, we would like to identify which factors affect
      employees' experiences in these settings. METHODS: This study followed a cross
      sectional study design, comparing usual care with UCCs. Data regarding employee
      experiences were collected from physicians, nurses, nurse practitioners, medical
      assistants and front desk personnel, by means of a questionnaire with scales
      regarding quality, workload and co-operation between the out-of-hours GP service
      and ED. Independent samples t-tests were used to determine mean differences
      between the settings. Multiple linear regression analyses were performed to test
      which items affected the perceived quality, workload and co-operation. RESULTS:
      The results showed that mutual co-operation alone was perceived as significantly
      better in UCCs compared to usual care. If divided between employers, no
      differences were found in the employee experiences working in out-of-hours GP
      services. ED employees in UCCs experienced a significantly better co-operation
      with their GP colleagues than their peers in the usual care setting, but also a
      higher workload. Remarkably, ED employees were less satisfied in general. The
      multiple regression model showed that perceived quality, workload and co
      operation were interrelated. Co-operation was the only aspect that was rated
      higher in the UCC setting. CONCLUSION: While perceived quality is equal and co
      operation between out-of-hours GP service and ED is better, the objective and
      perceived ED workload was higher in UCCs compared to usual care. Though UCCs
      relieve the pressure on EDs concerning the number of patients, they seem to
      aggravate the workload. EDs need to be careful not to excessively adjust staff
      capacity when responding to lower numbers of patients.

PMID- 29454379
TI  - Resistance to deltamethrin by domestic and wild Triatoma infestans populations in
      the municipality of Toro Toro, Potosi, Bolivia.
AB  - BACKGROUND: Chemical control with pyrethroid insecticides has been effective in
      reducing endemic areas of distribution of Triatoma infestans in the Southern
      Cone, as well as Bolivia; this had considerably reduced the infestation of
      households in a large part of the territory. Nowadays, areas such as the Chaco
      and the Inter-Andean Valleys are regions where the reach of vector control
      strategies is becoming limited, and infestations of insecticide-treated
      households are reported more often. The objective of this study was to determine
      if the persistence of T. infestans stems from changes in the susceptibility of
      its toxicological profile in four communities in the municipality of Toro Toro,
      Potosi, Bolivia. METHODS: Susceptibility to deltamethrin of wild and domestic
      populations of T. infestans was evaluated in two stages (16 populations before
      and 13 populations after spraying) among DUs (structures in the intra- and
      peridomicile) and wild ecotopes, in four communities. Serial dilutions of
      deltamethrin in acetone (0.2 MUl) were applied topically on standardized first
      stage nymphs. Dose-response results were analyzed with the software PoloPlus and
      the relationships between lethal doses (LD) and resistance ratios (RR50) were
      determined. RESULTS: Different degrees of RR50 were detected among the
      populations before and after spraying (25.66-54.70 and 21.91-40.67,
      respectively), as well as in different ecotopes within a DU (DU JC 3, 28.06
      36.13, in mixed structures of corrals and chicken coops; and DU JG 3, 46.27
      25.70, in kitchen roofs), or in the wild environment of the community JG Sil
      (29.21-40.67). The mortality of insects undergoing diagnostic dose (DD) was never
      higher than 34%. CONCLUSION: The results obtained in this study showed resistance
      of T. infestans to deltamethrin in four communities, hence the complexity of this
      phenomenon is not only limited to the level of communities, but also applies to
      the microgeographical level, as in different ecotopes present within the DUs.
      This phenomenon should be considered while planning the activities of control
      programs.

PMID- 29454380
TI  - Quality of life, satisfaction and outcomes after ministernotomy versus full
      sternotomy isolated aortic valve replacement (QUALITY-AVR): study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: During the last decade, the use of ministernotomy in cardiac surgery
      has increased. Quality of life and patient satisfaction after ministernotomy have
      never been compared to conventional full sternotomy in randomised trials. The aim
      of the study is to determine if this minimally invasive approach improves quality
      of life, satisfaction and clinical morbimortality outcomes. METHODS/DESIGN: The
      QUALITY-AVR trial is a single-blind, single-centre, independent, and pragmatic
      randomised clinical trial comparing ministernotomy ("J" shaped upper
      hemisternotomy toward right 4th intercostal space) to full sternotomy in patients
      with isolated severe aortic stenosis scheduled for elective aortic valve
      replacement. One hundred patients will be randomised in a 1:1 computational
      fashion. Sample size was determined for the primary end point with alpha error of
      0.05 and with power of 90% in detecting differences between intervention groups
      of >= 0.10 points in change from baseline quality of life Questionnaire EuroQOL
      index (EQ-5D-5 L(r)), measured at 1, 6 or 12 months. Secondary endpoints are: the
      differences in change from other baseline EQ-5D-5 L(r) utilities (visual analogue
      scale, Health Index and Severity Index), cardiac surgery specific satisfaction
      questionnaire (SATISCORE(r)), a combined safety endpoint of four major adverse
      complications at 1 month (all-cause mortality, acute myocardial infarction,
      neurologic events and acute renal failure), bleeding through drains within the
      first 24 h, intubation time, postoperative hospital and intensive care unit
      length of stay, transfusion needs during the first 72 h and 1-year survival
      rates. Clinical follow up is scheduled at baseline, 1, 6, and 12 months after
      randomization. All clinical outcomes are recorded following the Valve Academic
      Research Consortium 2 criteria. DISCUSSION: The QUALITY-AVR trial aims to test
      the hypothesis that ministernotomy improves quality of life, satisfaction and
      clinical outcomes in patients referred for isolated aortic valve replacement.
      Statistically significant differences favouring ministernotomy could modify the
      surgical "gold standard" for aortic stenosis surgery, and subsequently the need
      to change the control group in transcatheter aortic valve implantation trials.
      Recruitment started on 18 March 2016. In November 2017, 75 patients were
      enrolled. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02726087 . Registered on 13
      March 2016.

PMID- 29454381
TI  - Human cerebrovascular function in health and disease: insights from integrative
      approaches.
AB  - BACKGROUND: The marked increase in the size of the brain, and consequently, in
      neural processing capability, throughout human evolution is the basis of the
      higher cognitive function in humans. However, greater neural, and thus
      information processing capability, comes at a significant metabolic cost; despite
      its relatively small size, the modern human brain consumes almost a quarter of
      the glucose and oxygen supply in the human body. Fortunately, several vascular
      mechanisms ensure sufficient delivery of glucose and oxygen to the active neural
      tissue (neurovascular coupling), prompt removal of neural metabolic by-products
      (cerebral vasoreactivity), and constant global blood supply despite daily
      variations in perfusion pressure (cerebral autoregulation). The aim of this
      review is to provide an integrated overview of the available data on these
      vascular mechanisms and their underlying physiology. We also briefly review
      modern experimental approaches to assess these mechanisms in humans, and further
      highlight the importance of these mechanisms for humans' evolutionary success by
      providing examples of their healthy adaptations as well as pathophysiological
      alterations. CONCLUSIONS: Data reviewed in this paper demonstrate the importance
      of the cerebrovascular function to support humans' unique ability to form new and
      different interactions with each other and their surroundings. This highlights
      that there is much insight into the neural and cognitive functions that could be
      gleaned from interrogating the cerebrovascular function.

PMID- 29454382
TI  - High risk human papillomavirus prevalence and genotype distribution among women
      infected with HIV in Manaus, Amazonas.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-positive women have a high
      prevalence of human papillomavirus (HPV), and are infected with a broader range
      of HPV types than HIV-negative women. We aimed to determine the prevalence of
      cervical cytologic abnormalities, high-risk (HR)-HPV prevalence, type
      distribution according to the severity of cervical lesions and CD4 cell count and
      identify factors associated with HR-HPV infection among women living with HIV in
      Manaus, Amazonas. METHODS: We enrolled 325 women living with HIV that attended an
      infectious diseases referral hospital. Each woman underwent a gynecological exam,
      cervical cytology, HR-HPV detection by Polymerase chain Reaction (PCR) using the
      BD OnclarityTM HPV Assay, colposcopy and biopsy, when necessary. We assessed the
      associations between potential risk factors and HR-HPV infection. RESULTS:
      Overall, 299 (92.0%) women had a PCR result. The prevalence of HR-HPV- infection
      was 31.1%. The most prevalent HR-HPV types were: 56/59/66 (32.2%), 35/39/68
      (28.0%), 52 (21.5%), 16 (19.4%), and 45 (12.9%). Among the women with HR-HPV
      infection (n = 93), 43.0% had multiple infections. Women with HPV infection
      showed higher prevalence of cervical abnormalities than that HPV-negative (LSIL:
      22.6% vs. 1.5%; HSIL: 10.8% vs. 0.0%). The prevalence of HR-HPV among women with
      cytological abnormalities was 87.5% for LSIL and 100.0% for HSIL. Women with CD4
      < 200 cell/mm3 showed the highest HR-HPV prevalence (59.3%) although this trend
      was not statistically significant (p-value = 0.62). The mean CD4 cell count
      decreased with increasing severity of cervical lesions (p-value = 0.001). The
      multivariable analysis showed that increasing age was associated with a decreased
      risk of HR-HPV infection with an adjusted prevalence odds ratio of 0.9 (95.0% CI:
      0.9-1.0, p-value: 0.03) for each additional year. The only factor statistically
      significant associated with HR-HPV infection was CD4 cell count. CONCLUSIONS: HR
      HPV and abnormal cytology prevalence are high among women in the Amazonas. The
      low CD4 cell count was an important determinant of HPV infection and abnormal
      cytological findings. HPV quadrivalent vaccination used in Brazil might not offer
      protection for an important fraction of HPV-related disease burden in women
      living with HIV. This is partly explained by the high presence of non targeted
      vaccine HR-HPVs, such as the HPV genotype groups 56/59/66, 35/39/68 and
      individually HPV-52 and HPV-45, some of which contribute to high-grade lesion.

PMID- 29454383
TI  - Multidimensional needs of patients living and dying with heart failure in Kenya:
      a serial interview study.
AB  - BACKGROUND: Heart failure is an emerging challenge for Sub Saharan Africa.
      However, research on patients' needs and experiences of care is scarce with
      little evidence available to support and develop services. We aimed to explore
      the experiences of patients living and dying with heart failure in Kenya.
      METHODS: We purposively recruited 18 patients admitted with advanced heart
      failure at a rural district hospital in Kenya. We conducted serial in depth
      interviews with patients at 0, 3 and 6 months after recruitment, and conducted
      bereavement interviews with carers. Interviews were recorded, transcribed into
      English and analyzed using a thematic approach, assisted by Nvivo software
      package. RESULTS: Forty-four interviews were conducted. Patients experienced
      physical, psychosocial, spiritual and financial distress. They also had unmet
      needs for information about their illness, how it would affect them and how they
      could get better. Patients experience of and their interpretation of symptoms
      influenced health care seeking. Patients with acute symptoms sought care earlier
      than those with more gradual symptoms which tended to be normalised as part of
      daily life or assumed to be linked to common treatable conditions. Nearly all
      patients expected to be cured and were frustrated by a progressive illness poorly
      responsive to treatment. Accumulating costs was a barrier to continuity of care
      and caused tensions in social relationships. Patients valued information on the
      nature of their illness, prognosis, self-care, lifestyle changes and prevention
      strategies, but this was rarely available. CONCLUSIONS: This is the first in
      depth study to explore the experiences of people living with advanced heart
      failure in Kenya. This study suggests that patients would benefit from holistic
      care, such as a palliative approach that is aimed at providing multidimensional
      symptom management. A palliative approach to services should be provided
      alongside chronic disease management aimed at primary prevention of risk factors,
      and early identification and initiation of disease modifying therapy. Further
      research is needed to determine best practice for integrating palliative care for
      people living and dying with heart failure.

PMID- 29454384
TI  - APPLaUD: access for patients and participants to individual level uninterpreted
      genomic data.
AB  - BACKGROUND: There is a growing support for the stance that patients and research
      participants should have better and easier access to their raw (uninterpreted)
      genomic sequence data in both clinical and research contexts. MAIN BODY: We
      review legal frameworks and literature on the benefits, risks, and practical
      barriers of providing individuals access to their data. We also survey genomic
      sequencing initiatives that provide or plan to provide individual access. Many
      patients and research participants expect to be able to access their health and
      genomic data. Individuals have a legal right to access their genomic data in some
      countries and contexts. Moreover, increasing numbers of participatory research
      projects, direct-to-consumer genetic testing companies, and now major national
      sequencing initiatives grant individuals access to their genomic sequence data
      upon request. CONCLUSION: Drawing on current practice and regulatory analysis, we
      outline legal, ethical, and practical guidance for genomic sequencing initiatives
      seeking to offer interested patients and participants access to their raw genomic
      data.

PMID- 29454385
TI  - Tranexamic acid in total shoulder arthroplasty and reverse shoulder arthroplasty:
      a systematic review and meta-analysis.
AB  - BACKGROUND: The effects of tranexamic acid (TXA) in the setting of shoulder
      arthroplasty are unclear. The objective of this study was to examine the effects
      of TXA in reducing the need for blood transfusions and blood loss in patients
      undergoing primary total shoulder arthroplasty (TSA) and reverse total shoulder
      arthroplasty (RTSA). METHODS: We conducted a systematic review and meta-analysis
      of randomized controlled trials (RCTs) and retrospective cohort studies (RCS)
      that compared outcomes of patients who did and did not receive TXA during TSA or
      RTSA. We searched Cochrane Central Register of Controlled Trials, EMBASE, and
      MEDLINE for relevant studies. We assessed the risk of bias of the included
      studies and calculated pooled risk estimates. The primary outcome was transfusion
      rate, and secondary outcomes were changes in hemoglobin, estimated total blood
      loss (ETBL), blood loss via drainage, operative time, hospital stay, overall
      complications, and thromboembolic events. RESULTS: We identified 3 RCTs and 3 RCS
      including 677 patients with 680 shoulders (343 TXA and 337 non-TXA). The random
      effects model meta-analysis showed that TXA group had a lower transfusion rate
      (risk ratio (RR) 0.34, 95% CI 0.14 to 0.79), less change in hemoglobin (mean
      difference (MD) -0.64 g/dl, 95% CI -0.81 to - 0.46), and reduced ETBL (MD -249.24
      ml, 95% CI -338.74 to - 159.74). In patients with RTSA, the TXA group had a lower
      transfusion rate (RR 0.28, 95% CI 0.14 to 0.79), less ETBL (MD -249.15 ml, 95% CI
      -426.60 to - 71.70), less change in hemoglobin (MD - 0.64 g/dl, 95% CI -0.86 to -
      0.42), and less blood loss via drainage (MD - 84.56 ml, 95% CI -145.72.14 to -
      23.39) than non-TXA group. CONCLUSIONS: The use of TXA in primary shoulder
      arthroplasty appears safe, and can reduce transfusion rate, changes in
      hemoglobin, and perioperative total blood loss, especially in patients with RTSA.
      LEVEL OF EVIDENCE: Systematic Review and meta-analysis, III.

PMID- 29454386
TI  - Telomere elongation protects heart and lung tissue cells from fatal damage in
      rats exposed to severe hypoxia.
AB  - BACKGROUND: The effects of acute hypoxia at high altitude on the telomere length
      of the cells in the heart and lung tissues remain unclear. This study aimed to
      investigate the change in telomere length of rat heart and lung tissue cells in
      response to acute exposure to severe hypoxia and its role in hypoxia-induced
      damage to heart and lung tissues. METHODS: Forty male Wistar rats (6-week old)
      were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in
      control group were kept at an altitude of 1500 m, while rats in hypoxia group
      were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure
      oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right
      middle lobe tissues of each rat were collected for measurement of telomere length
      and reactive oxygen species (ROS) content, and the mRNA and protein levels of
      telomerase reverse transcriptase (TERT), hypoxia-inducible factor1alpha (HIF
      1alpha), and hypoxia-inducible factor1alpha (HIF-2alpha). RESULTS: Increased
      exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS
      production and telomere length. The mRNA and protein levels of TERT and HIF
      1alpha were significantly higher in rats exposed to hypoxia and increased with
      prolonged exposure; mRNA and protein levels of HIF-2alpha increased only in rats
      exposed to hypoxia for 7 days. TERT was positively correlated with telomere
      length and the levels of HIF-1alpha but not HIF-2alpha. CONCLUSIONS: Acute
      exposure to severe hypoxia causes damage to heart and lung tissues due to the
      production of ROS but promotes telomere length and adaptive response by
      upregulating TERT and HIF-1alpha, which protect heart and lung tissue cells from
      fatal damage.

PMID- 29454387
TI  - The transcriptome response of the ruminal methanogen Methanobrevibacter
      ruminantium strain M1 to the inhibitor lauric acid.
AB  - OBJECTIVE: Lauric acid (C12) is a medium-chain fatty acid that inhibits growth
      and production of the greenhouse gas methane by rumen methanogens such as
      Methanobrevibacter ruminantium. To understand the inhibitory mechanism of C12, a
      transcriptome analysis was performed in M. ruminantium strain M1 (DSM 1093) using
      RNA-Seq. RESULTS: Pure cell cultures in the exponential growth phase were treated
      with 0.4 mg/ml C12, dissolved in dimethyl sulfoxide (DMSO), for 1 h and
      transcriptomic changes were compared to DMSO-only treated cells (final DMSO
      concentration 0.2%). Exposure to C12 resulted in differential expression of 163
      of the 2280 genes in the M1 genome (maximum log2-fold change 6.6). Remarkably,
      C12 hardly affected the expression of genes involved in methanogenesis. Instead,
      most affected genes encode cell-surface associated proteins (adhesion-like
      proteins, membrane-associated transporters and hydrogenases), and proteins
      involved in detoxification or DNA-repair processes. Enrichment analysis on the
      genes regulated in the C12-treated group showed a significant enrichment for
      categories 'cell surface' and 'mobile elements' (activated by C12), and for the
      categories 'regulation' and 'protein fate' (represssed). These results are useful
      to generate and test specific hypotheses on the mechanism how C12 affects rumen
      methanogens.

PMID- 29454388
TI  - DOCK7-ANGPTL3 SNPs and their haplotypes with serum lipid levels and the risk of
      coronary artery disease and ischemic stroke.
AB  - BACKGROUND: Little is known about the association of the dedicator of cytokinesis
      7 (DOCK7 rs1748195) and angiopoietin like 3 (ANGPTL3 rs12563308) single
      nucleotide polymorphisms (SNPs) and their haplotypes with serum lipid levels and
      the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese
      populations. This study aimed to detect such association in a Southern Chinese
      Han population. METHODS: This study included 1728 subjects (CAD, 568; IS, 539;
      and controls, 621). Genotypes of the two SNPs were determined by the Snapshot
      technology. RESULTS: The genotypic and allelic frequencies of the rs1748195 SNP
      were different between CAD patients and controls (P < 0.05 for each), the
      rs1748195G allele frequency was higher in CAD patients than in controls (27.6%
      vs. 23.6%, P = 0.024). The genotypic frequencies of the rs12563308 SNP were also
      different between CAD patients and controls (P = 0.021). The rs1748195 SNP was
      associated with an increased risk of CAD after controlling for potential
      confounders and Bonferroni correction (P < 0.025 considered statistically
      significant; Recessive: OR = 1.79, 95% CI = 1.04-3.06, P = 0.017; Log-additive:
      OR = 1.27, 95% CI = 1.02-1.57, P = 0.014), whereas the rs12563308 SNP was
      associated with a decreased risk of CAD (Dominant: OR = 0.69, 95% CI = 0.45-0.94,
      P = 0.011; Log-additive: OR = 0.73, 95% CI = 0.49-0.89, P = 0.009). The rs1748195
      SNP was also associated with an increased risk of severity to coronary artery
      atherosclerosis (Dominant: OR = 1.45, 95% CI = 1.07-2.11, P = 0.017; Log
      additive: OR = 1.35, 95% CI = 1.09-1.82, P = 0.013). The interactions of SNP
      environment on serum lipid levels and the risk of severity to coronary artery
      atherosclerosis, CAD and IS were noted. The rs1748195G-rs12563308T haplotype was
      associated with an increased angiographic severity to coronary artery
      atherosclerosis (OR = 1.46, 95% CI = 1.05-2.03), and the risk of CAD (OR = 1.37,
      95% CI = 1.08-1.74). The interactions of haplotype-hypertension on the risk of
      CAD and haplotype-drinking on the risk of CAD/IS were observed. CONCLUSIONS:
      These results suggest that the DOCK-ANGPTL3 SNPs and their haplotypes were
      associated with the angiographic severity to coronary artery atherosclerosis and
      the risk of CAD and IS in the Southern Chinese Han population.

PMID- 29454389
TI  - Recruitment of racial and ethnic minorities to clinical trials conducted within
      specialty clinics: an intervention mapping approach.
AB  - BACKGROUND: Despite efforts to increase diversity in clinical trials,
      racial/ethnic minority groups generally remain underrepresented, limiting
      researchers' ability to test the efficacy and safety of new interventions across
      diverse populations. We describe the use of a systematic framework, intervention
      mapping (IM), to develop an intervention to modify recruitment behaviors of
      coordinators and specialist investigators with the goal of increasing diversity
      in trials conducted within specialty clinics. To our knowledge IM has not been
      used in this setting. METHODS: The IM framework was used to ensure that the
      intervention components were guided by health behavior theories and the evidence.
      The IM steps consisted of (1) conducting a needs assessment, (2) identification
      of determinants and objectives, (3) selection of theory-informed methods and
      practical applications, (4) development and creation of program components, (5)
      development of an adoption and implementation plan, and (6) creation of an
      evaluation plan. RESULTS: The intervention included five educational modules, one
      in-person and four web-based, plus technical assistance calls to coordinators.
      Modules addressed the intervention rationale, development of clinic-specific
      plans to obtain minority-serving physician referrals, physician-centered and
      patient-centered communication, and patient navigation. The evaluation, a
      randomized trial, was recently completed in 50 specialty clinics and is under
      analysis. CONCLUSIONS: Using IM we developed a recruitment intervention that
      focused on building relationships with minority-serving physicians to encourage
      minority patient referrals. IM enhanced our understanding of factors that may
      influence minority recruitment and helped us integrate strategies from multiple
      disciplines that were relevant for our audience.

PMID- 29454390
TI  - Promoting public access to clinical trial protocols: challenges and
      recommendations.
AB  - BACKGROUND: Recognizing the value of promoting public access to clinical trial
      protocols, Trials pioneered the way for their publication over a decade ago.
      However, despite major advances in the public accessibility of information about
      trial methods and results, protocol sharing remains relatively rare. MAIN BODY:
      Protocol sharing facilitates the critical appraisal of clinical trials and helps
      to identify and deter the selective reporting of outcomes and analyses.
      Challenges to the routine availability of high quality trial protocols include
      the gaps in incentives and adherence mechanisms, limited venues for sharing the
      original and final protocol versions, and the need for mechanisms to ensure
      transparent and complete protocol content. CONCLUSIONS: We propose
      recommendations for addressing key challenges to protocol sharing in order to
      promote routine public access to protocols for the benefit of patients and other
      users of evidence from clinical trials.

PMID- 29454392
TI  - Soft robotic devices for hand rehabilitation and assistance: a narrative review.
AB  - INTRODUCTION: The debilitating effects on hand function from a number of a
      neurologic disorders has given rise to the development of rehabilitative robotic
      devices aimed at restoring hand function in these patients. To combat the
      shortcomings of previous traditional robotics, soft robotics are rapidly emerging
      as an alternative due to their inherent safety, less complex designs, and
      increased potential for portability and efficacy. While several groups have begun
      designing devices, there are few devices that have progressed enough to provide
      clinical evidence of their design's therapeutic abilities. Therefore, a global
      review of devices that have been previously attempted could facilitate the
      development of new and improved devices in the next step towards obtaining
      clinical proof of the rehabilitative effects of soft robotics in hand
      dysfunction. METHODS: A literature search was performed in SportDiscus, Pubmed,
      Scopus, and Web of Science for articles related to the design of soft robotic
      devices for hand rehabilitation. A framework of the key design elements of the
      devices was developed to ease the comparison of the various approaches to
      building them. This framework includes an analysis of the trends in portability,
      safety features, user intent detection methods, actuation systems, total DOF,
      number of independent actuators, device weight, evaluation metrics, and modes of
      rehabilitation. RESULTS: In this study, a total of 62 articles representing 44
      unique devices were identified and summarized according to the framework we
      developed to compare different design aspects. By far, the most common type of
      device was that which used a pneumatic actuator to guide finger
      flexion/extension. However, the remainder of our framework elements yielded more
      heterogeneous results. Consequently, those results are summarized and the
      advantages and disadvantages of many design choices as well as their rationales
      were highlighted. CONCLUSION: The past 3 years has seen a rapid increase in the
      development of soft robotic devices for hand rehabilitative applications. These
      mostly preclinical research prototypes display a wide range of technical
      solutions which have been highlighted in the framework developed in this
      analysis. More work needs to be done in actuator design, safety, and
      implementation in order for these devices to progress to clinical trials. It is
      our goal that this review will guide future developers through the various design
      considerations in order to develop better devices for patients with hand
      impairments.

PMID- 29454391
TI  - Type 1 diabetes susceptibility alleles are associated with distinct alterations
      in the gut microbiota.
AB  - BACKGROUND: Dysbiosis of the gut microbiota has been implicated in the
      pathogenesis of many autoimmune conditions including type 1 diabetes (T1D). It is
      unknown whether changes in the gut microbiota observed in T1D are due to
      environmental drivers, genetic risk factors, or both. Here, we have performed an
      analysis of associations between the gut microbiota and T1D genetic risk using
      the non-obese diabetic (NOD) mouse model of T1D and the TwinsUK cohort. RESULTS:
      Through the analysis of five separate colonies of T1D susceptible NOD mice, we
      identified similarities in NOD microbiome that were independent of animal
      facility. Introduction of disease protective alleles at the Idd3 and Idd5 loci
      (IL2, Ctla4, Slc11a1, and Acadl) resulted in significant alterations in the NOD
      microbiome. Disease-protected strains exhibited a restoration of immune
      regulatory pathways within the gut which could also be reestablished using IL-2
      therapy. Increased T1D disease risk from IL-2 pathway loci in the TwinsUK cohort
      of human subjects resulted in some similar microbiota changes to those observed
      in the NOD mouse. CONCLUSIONS: These findings demonstrate for the first time that
      type 1 diabetes-associated genetic variants that restore immune tolerance to
      islet antigens also result in functional changes in the gut immune system and
      resultant changes in the microbiota.

PMID- 29454393
TI  - Health professionals' perceptions about their clinical performance and the
      influence of audit and feedback on their intentions to improve practice: a theory
      based study in Dutch intensive care units.
AB  - BACKGROUND: Audit and feedback aims to guide health professionals in improving
      aspects of their practice that need it most. Evidence suggests that feedback
      fails to increase accuracy of professional perceptions about clinical
      performance, which likely reduces audit and feedback effectiveness. This study
      investigates health professionals' perceptions about their clinical performance
      and the influence of feedback on their intentions to change practice. METHODS: We
      conducted an online laboratory experiment guided by Control Theory with 72
      intensive care professionals from 21 units. For each of four new pain management
      indicators, we collected professionals' perceptions about their clinical
      performance; peer performance; targets; and improvement intentions before and
      after receiving first-time feedback. An electronic audit and feedback dashboard
      provided ICU's own performance, median and top 10% peer performance, and
      improvement recommendations. The experiment took place approximately 1 month
      before units enrolled into a cluster-randomised trial assessing the impact of
      adding a toolbox with suggested actions and materials to improve intensive care
      pain management. During the experiment, the toolbox was inaccessible; all
      participants accessed the same version of the dashboard. RESULTS: We analysed 288
      observations. In 53.8%, intensive care professionals overestimated their clinical
      performance; but in only 13.5%, they underestimated it. On average, performance
      was overestimated by 22.9% (on a 0-100% scale). Professionals similarly
      overestimated peer performance, and set targets 20.3% higher than the top
      performance benchmarks. In 68.4% of cases, intentions to improve practice were
      consistent with actual gaps in performance, even before professionals had
      received feedback; which increased to 79.9% after receiving feedback (odds ratio,
      2.41; 95% CI, 1.53 to 3.78). However, in 56.3% of cases, professionals still
      wanted to improve care aspects at which they were already top performers.
      Alternatively, in 8.3% of cases, they lacked improvement intentions because they
      did not consider indicators important; did not trust the data; or deemed
      benchmarks unrealistic. CONCLUSIONS: Audit and feedback helps health
      professionals to work on aspects for which improvement is recommended. Given the
      abundance of professionals' prior good improvement intentions, the limited
      effects typically found by audit and feedback studies are likely predominantly
      caused by barriers to translation of intentions into actual change in clinical
      practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT02922101 . Registered 26
      September 2016.

PMID- 29454394
TI  - Therapeutic antagonism of ANGPTL4.

PMID- 29454395
TI  - Kounis syndrome: New classification.

PMID- 29454396
TI  - Dietary ellagic acid is protective for atherosclerosis.

PMID- 29454397
TI  - Response to letter "Dietary ellagic acid is protective for atherosclerosis".

PMID- 29454398
TI  - An interesting correlation between patent foramen ovale and migraine.

PMID- 29454399
TI  - Reply to the Letter to the Editors: "Takotsubo syndrome: Still a benign entity?"

PMID- 29454400
TI  - Comment on the original paper entitled "The effect of Ezetimibe and Simvastatin
      Combination Therapy on percutaneous coronary intervention patients".

PMID- 29454401
TI  - Inhibition of TGF-beta1 might be a novel therapeutic target in the treatment of
      cardiac fibrosis.

PMID- 29454402
TI  - ANGPTL4, a multifaceted protein at the cross-talk between metabolism and
      cardiovascular disorders.

PMID- 29454403
TI  - Response to inhibition of TGF-beta1 might be a novel therapeutic target in the
      treatment of cardiac fibrosis.

PMID- 29454404
TI  - Is the decrease of triglyceride level after acute myocardial infarction within a
      month by the effect of combination therapy of Ezetimibe and Simvastatin.

PMID- 29454405
TI  - Response to letter regarding article by Formiga et al., "Utility of the
      Controlling Nutritional Status (CONUT) score in patients admitted due to acute
      heart failure".

PMID- 29454406
TI  - Letter regarding Nakamura et al. "Anatomical relationship of coronary sinus/great
      cardiac vein and left circumflex coronary artery along mitral annulus in atrial
      fibrillation before radiofrequency catheter ablation using 320-slice CT".

PMID- 29454407
TI  - Letter to the editor: A simple sarcopenia screening test predicts future adverse
      events in patients with heart failure.

PMID- 29454408
TI  - Reply to letter to the editor: "A simple sarcopenia screening test predicts
      future adverse events in patients with heart failure".

PMID- 29454409
TI  - Inhibition of NLRP1 inflammasome might be a novel therapeutic target in the
      treatment of peripheral arterial disease.

PMID- 29454410
TI  - Possible use of fondaparinux in heparin-induced thrombocytopenia.

PMID- 29454411
TI  - Identification of a potential inhibitor of NLRP1 inflammasome for the treatment
      of peripheral arterial disease.

PMID- 29454412
TI  - VEGF165b elevation in pulmonary arterial hypertension patients, causative or
      adaptive?

PMID- 29454413
TI  - VEGF165b elevation in pulmonary arterial hypertension patients, causative or
      adaptive? -Reply.

PMID- 29454414
TI  - Inhibition of myeloperoxidase might be a novel therapeutic target in the
      treatment of atherosclerosis.

PMID- 29454415
TI  - Inhibition of parkin might be a novel therapeutic target for 'Browning' the
      cardiac adipose tissues.

PMID- 29454416
TI  - HMGA1: A novel predisposing gene for acute myocardial infarction.

PMID- 29454417
TI  - Comment on Li et al. HMGA1: A novel predisposing gene for acute myocardial
      infarction.

PMID- 29454418
TI  - Could direct oral anticoagulants be an alternative to vitamin K antagonists in
      patients with hypertrophic cardiomyopathy and atrial fibrillation?

PMID- 29454419
TI  - Reply to letter of Dr. Bandyopadhyay on "Possible use of fondaparinux in heparin
      induced thrombocytopenia".

PMID- 29454420
TI  - Role of quantitative myocardial-iron in hemodialysis-dependent end-stage renal
      disease subjects.

PMID- 29454421
TI  - Oligonucleotides targeting ANGPTL3.

PMID- 29454422
TI  - Concerns About the Integrity of Sato et al. Am J Med. 2005;118:1250-1255.

PMID- 29454423
TI  - Statement of Concern Regarding: Sato Y, Iwamoto J, Kanoko T, Satoh K.
      Homocysteine as a Predictive Factor for Hip Fracture in Elderly Women with
      Parkinson's Disease. Am J Med. 2005;118:1250-1255.

PMID- 29454424
TI  - Dissemination of Coronary Care Units Versus Geriatric Units.

PMID- 29454425
TI  - The Reply.

PMID- 29454426
TI  - Primary Care Training Must Change.

PMID- 29454427
TI  - The Reply.

PMID- 29454428
TI  - Role of Cholelithiasis in Development of Portal Vein Aneurysm.

PMID- 29454430
TI  - Prevention of Central Venous Catheter Removal-Associated Air Embolization.

PMID- 29454429
TI  - The Reply.

PMID- 29454431
TI  - The Reply.

PMID- 29454432
TI  - Hemoglobin and Change in Hemoglobin Status: Comments on Methodology.

PMID- 29454433
TI  - The Reply.

PMID- 29454434
TI  - Hemorrhagic Brain Metastases as a Diagnosis of Exclusion: A Diagnostic Dilemma.

PMID- 29454435
TI  - Arteriolar Injury in Hypertension.

PMID- 29454436
TI  - Invited commentary.

PMID- 29454437
TI  - Invited commentary.

PMID- 29454438
TI  - Therapeutic lymphangiography for traumatic chylothorax.
AB  - Chylothorax is a challenging disease. We present a case of traumatic chylothorax
      that was successfully treated using lymphangiography through intranodal injection
      of contrast agent. A 17-year-old girl had chylothorax. It did not improve despite
      medical treatment. We performed lymphangiography through intranodal injection of
      an oil contrast agent (Lipiodol). The amount of chylothorax was reduced from 1000
      to 120 mL/d, and we could remove the thoracotomy tube. Thereafter, although she
      had a small amount of pleural effusion, she has not demonstrated aggravation for
      19 months. Lymphangiography with oil contrast agent can be one of the options to
      treat chylothorax.

PMID- 29454439
TI  - Management of an enormous inferior mesenteric vein aneurysm.
AB  - Venous aneurysms are rare entities, with mesenteric venous aneurysms among the
      rarest reported. We present a case of a 66-year-old man with abdominal pain
      secondary to an enormous 7.8-cm inferior mesenteric vein aneurysm. In addition,
      he had evidence of other venous abnormalities, including bilateral leg chronic
      venous insufficiency and a right varicocele. This appears to be the only reported
      case of an isolated inferior mesenteric vein aneurysm. Adding to its
      significance, this aneurysm is among the largest of any mesenteric vein aneurysm
      reported. Given the rupture risk, laparoscopic ligation above the aneurysm was
      performed.

PMID- 29454440
TI  - Giant cephalic vein aneurysm in a kidney transplant recipient with a
      brachiocephalic fistula and recurrent stenosis of the left brachiocephalic vein.

PMID- 29454441
TI  - The hemodynamic effects of pregnancy on the lower extremity venous system.
AB  - OBJECTIVE: Pregnancy has significant effects on the lower extremity venous
      system. Increasing venous pressure and blood volume, in combination with reduced
      flow rates within the deep veins, predisposes pregnant women to both primary and
      secondary chronic venous insufficiency (CVI). This review article highlights the
      specific physiologic and hemodynamic changes that occur during pregnancy and
      examines the nonpharmacologic, pharmacologic, and invasive interventions that are
      appropriate for both prophylaxis and treatment of CVI and venous thromboembolism
      (VTE). METHODS: This study is a review article of the key literature related to
      VTE and CVI in pregnancy. RESULTS: Significant hemodynamic changes occur in the
      lower extremities during pregnancy. Although well documented and essential to
      fetal development, these changes can have a negative impact on the maternal lower
      extremity venous circulation. Consequences of pregnancy can result in venous
      disease only during pregnancy or, particularly in the multiparous patient, can
      progress to CVI. An abundance of literature and guidelines exist for the
      management of VTE during pregnancy; however, the quality and extent of literature
      based around the management of primary CVI during pregnancy are modest at best.
      CONCLUSIONS: The physiologic changes throughout the arterial and venous systems
      during pregnancy are well documented. However, there is a paucity of data
      available to construct guidelines for care, particularly in the pregnant patient
      with symptomatic superficial venous insufficiency. Further investigation in the
      form of prospective randomized trials is required to establish appropriate
      guidelines for treatment.

PMID- 29454442
TI  - Site of service in the Quality Payment Program.

PMID- 29454443
TI  - Regarding "Management of refractory chylous ascites with peritoneovenous shunts".

PMID- 29454444
TI  - Minimally invasive pancreatoduodenectomy: is the incidence of clinically relevant
      postoperative pancreatic fistula comparable to that after open
      pancreatoduodenectomy?
AB  - BACKGROUND: Studies evaluating the efficacy of minimally invasive approaches to
      pancreatoduodenectomy (MIS-PD) compared to open pancreatioduodenectomy (OPD) have
      been limited by selection bias and mixed outcomes. METHODS: ACS-NSQIP 2014-2015
      pancreas procedure-targeted data were used to identify patients undergoing PD.
      Intention-to-treat analysis was performed. RESULTS: Of 7907 PD patients, 1277
      (16%) underwent MIS-PD: 776 (61%) robotic or laparoscopic PD, 304 (24%) hybrid,
      and 197 (15%) unplanned conversions. There were no differences in demographics or
      comorbidities. Patients undergoing MIS-PD were less likely to have pancreatic
      ductal adenocarcinoma (30.9% vs 53.9%, P < 0.01) and less likely to have a
      dilated pancreatic duct (21.8% vs 46.7%, P < 0.01). 30-day morbidity was less for
      MIS-PD (63.6% vs 76.9%, P < 0.01), due to decreased delayed gastric emptying DGE)
      in the MIS-PD group (8.6% vs 15.5%, P < 0.01). 30-day mortality, length-of-stay,
      and readmissions were not significantly different. Patients undergoing MIS-PD had
      greater rates of CR-POPF (15.3% vs 13.0%, P = 0.03). On adjusted multivariable
      analysis, MIS-PD was not associated with CR-POPF (OR 1.05, 95% CI 0.87-1.26) but
      was associated with decreased DGE (OR 0.57, 95% CI 0.46-0.71). CONCLUSION: MIS-PD
      has comparable short-term outcomes to open PD. While CR-POPF rates are greater
      for MIS-PD, this increased risk appears related to case-selection bias and not
      inherent to the MIS-approach.

PMID- 29454445
TI  - Devices and methods to improve colonoscopy completion (with videos).

PMID- 29454446
TI  - Competency in polypectomy: when desirable becomes essential.

PMID- 29454447
TI  - Managing the patient with colorectal adenomas found at an early age.

PMID- 29454448
TI  - Incomplete polyp resection: still searching for a solution.

PMID- 29454449
TI  - Adhering to quality metrics in colonoscopy: we can do better.

PMID- 29454450
TI  - Video-based performance assessment in endoscopy: Moving beyond "see one, do one,
      teach one"?

PMID- 29454451
TI  - Should the colonoscopy patient practice sex and age discrimination?

PMID- 29454452
TI  - Removing large rectal polyps: when the whole may be greater than the sum of its
      parts.

PMID- 29454453
TI  - Rectal EMR for enteric ganglia: Is deeper better?

PMID- 29454454
TI  - Should we use EMR to resect small colorectal polyps? The jury is still out.

PMID- 29454455
TI  - Response.

PMID- 29454456
TI  - Are small adenomas on initial colonoscopy really a risk factor for advanced
      neoplasia on surveillance colonoscopy?

PMID- 29454457
TI  - Response.

PMID- 29454458
TI  - Randomized controlled trial of scleroligation versus band ligation for
      eradication of gastroesophageal varices.

PMID- 29454459
TI  - Stent placement for hilar cholangiocarcinoma.

PMID- 29454460
TI  - Response.

PMID- 29454461
TI  - Fluoridation advocacy in referenda where media coverage is balanced yet biased.
AB  - BACKGROUND: Despite supporting scientific evidence, community water fluoridation
      (CWF) often fails in public referenda. To understand why, the authors
      quantitatively analyzed text from news media coverage of CWF referenda. METHODS:
      The authors analyzed text from 234 articles covering 11 CWF referenda conducted
      in 3 US cities from 1956 through 2013. The authors used cluster analysis to
      identify each article's core rhetoric and classified it according to sentiment
      and tone. The authors used multilevel count regression models to measure the use
      of positive and negative words regarding CWF. RESULTS: Media coverage more
      closely resembled core rhetoric used by fluoridation opponents than the rhetoric
      used by fluoridation proponents. Despite the scientific evidence, the media
      reports were balanced in tone and sentiment for and against CWF. However, in
      articles emphasizing children, greater negative sentiment was associated with CWF
      rejection. CONCLUSIONS: Media coverage depicted an artificial balance of evidence
      and tone in favor of and against CWF. The focus on children was associated with
      more negative tone in cities where voters rejected CWF. PRACTICAL IMPLICATIONS:
      When speaking to the media, advocates for CWF should emphasize benefits for
      children and use positive terms about dental health rather than negative terms
      about dental disease.

PMID- 29454462
TI  - Reply.

PMID- 29454463
TI  - A review on cationic lipids with different linkers for gene delivery.
AB  - Cationic lipids have become known as one of the most versatile tools for the
      delivery of DNA, RNA and many other therapeutic molecules, and are especially
      attractive because they can be easily designed, synthesized and characterized.
      Most of cationic lipids share the common structure of cationic head groups and
      hydrophobic portions with linker bonds between both domains. The linker bond is
      an important determinant of the chemical stability and biodegradability of
      cationic lipid, and further governs its transfection efficiency and cytotoxicity.
      Based on the structures of linker bonds, they can be grouped into many types,
      such as ether, ester, amide, carbamate, disulfide, urea, acylhydrazone,
      phosphate, and other unusual types (carnitine, vinyl ether, ketal, glutamic acid,
      aspartic acid, malonic acid diamide and dihydroxybenzene). This review summarizes
      some research results concerning the nature (such as the structure and
      orientation of linker groups) and density (such as the spacing and the number of
      linker groups) of linker bond for improving the chemical stability,
      biodegradability, transfection efficiency and cytotoxicity of cationic lipid to
      overcome the critical barriers of in vitro and in vivo transfection.

PMID- 29454464
TI  - Prodrugs, phospholipids and vesicular delivery - An effective triumvirate of
      pharmacosomes.
AB  - With the advent from the laboratory bench to patient bedside in last five
      decades, vesicular systems have now come to be widely accepted as pragmatic means
      for controlled delivery of drugs. Their success stories include those of
      liposomes, niosomes and even the lately developed ethosomes and transferosomes.
      Pharmacosomes, which, as delivery systems offer numerous advantages and have been
      widely researched, however, remain largely unacknowledged as a successful
      delivery system. Though a large number of drugs have been derivatized and
      formulated into self-assembled vesicular systems, the term pharmacosomes has not
      been widely used while reporting them. Therefore, their relative obscurity may be
      attributed to the non-usage of the nomenclature of pharmacosomes by the
      researchers working in the area. We present a review on the scenario that lead to
      origin of these bio-inspired vesicles composed of self-assembling amphiphilic
      molecules. Various drugs that have been formulated into pharmacosomes, their
      characterization techniques, their properties relative to those of other
      vesicular delivery systems, and the success achieved so far are also discussed.

PMID- 29454465
TI  - Fatigue as a mediator of the relationship between quality of life and mental
      health problems in hospital nurses.
AB  - The aims of this study were to investigate the relationships among quality of
      life (QoL), mental health problems and fatigue among hospital nurses, and to test
      whether fatigue and its multiple dimensions would mediate the effect of QoL on
      mental health problems. Data were collected using questionnaires (including the
      World Health Organization Quality of Life-BREF [WHOQOL-BREF], General Health
      Questionnaire [GHQ-12] and Multidimensional Fatigue Inventory [MFI-20] for
      evaluation of QoL, mental health problems and fatigue, respectively) from 990
      Iranian hospital nurses, and analysed by generalized structural equation
      modelling (GSEM). The results indicated that QoL, mental health problems and
      fatigue were interrelated, and supported the direct and indirect (through
      fatigue) effects of QoL on mental health problems. All domains of the WHOQOL
      BREF, and particularly physical (sleep problems), psychological (negative
      feelings) and environmental health (leisure activities) domains, were strongly
      related to the mental health status of the studied nurses. Fatigue and its
      multiple dimensions partially mediated the relationship between QoL and mental
      health problems. The results highlighted the importance of physical,
      psychological and environmental aspects of QoL and suggested the need for
      potential interventions to improve fatigue (particularly physical fatigue along
      with mental fatigue) and consequently mental health status of this working
      population. The findings have possible implications for nurses' health and
      patient safety outcomes.

PMID- 29454466
TI  - [Dermoid cysts of the posterior cerebral fossa in children revealed by recurrent
      aseptic meningitis: Report of two cases and a review of the literature].
AB  - INTRODUCTION: Dermoid cysts of central nervous system are very rare. The usual
      clinical presentation is dominated by intracranial hypertension, epilepsy and
      cranial palsy. The revelation mode could be recurrent aseptic meningitis. AIM:
      The aim of this case report is to consider the dermoid cyst as regards the
      differential diagnosis in children treated for recurrent aseptic meningitis to
      avoid misdiagnosis and ice qui a oriente le diagnostic a une meningitnadequate
      treatment. METHODS: Two children were admitted in the pediatric department for
      recurrent aseptic meningitis. The MRI confirmed the presence of a posterior fossa
      dermoid cyst. RESULTS: Loss of meningitis after microsurgical resection.
      CONCLUSION: The diagnosis of dermoid cyst is performed and reconsidered at an
      early stage in aseptic meningitis in order to establish an adequate therapy,
      which is surgery.

PMID- 29454467
TI  - Microvascular decompression for hemifacial spasm: Outcome on spasm and
      complications. A review.
AB  - Over the last decades microvascular decompression (MVD) has been established as
      the curative treatment of the primary Hemifacial Spasm (HFS), proven to be linked
      in almost all cases to a neurovascular compression of the facial nerve. Because
      the disease is not life-threatening and MVD not totally innocuous, efficacy and
      safety have to be weighted before decision taken of indicating surgery. The
      authors have been charged by the French Speaking Society of Neurosurgery to
      conduct a detailed evaluation of the probability of relief of the spasm that MVD
      is able to obtain, together with its potential complications. For the review, the
      authors have gone through the reports available from the Pubmed system. Eighty
      two publications have been read and analysed, totalizing more than 10,000
      operated cases. In most series, the percentage of patients with total relief
      ranged between 85% and 90%. Relief was obtained after a certain delay in as many
      as in 33%+/-8% of the patients in many series. For those, delay lasted around one
      year in 12% of them. When effect of MVD was considered achieved, relief remained
      permanent in all but 1%-2% of the long-term followed patients. As regards to
      complications, risk of permanent cranial nerve deficit was evaluated at 1%-2% for
      facial palsy, 2%-3% for non-functional hearing loss, 0.5%-1% for lower cranial
      nerve dysfunction. Risk of stroke was at 0.1% and mortality at 0.1%. CSF leakage
      and related complications could be reduced at less than 2% in most series
      provided careful closing techniques be applied. Complications were at a higher
      rate in repeated MVD. MVD is an effective curative method for almost all the
      patients affected with primary HFS. Because MVD for HFS is functional surgery,
      scrupulous consideration of its potential risks, together with the ways to avoid
      complications are of paramount importance. When MVD is estimated to have failed,
      it is wise to wait one year before considering to repeat surgery, as number of
      patients may benefit from delayed effect. This is the more so as important as
      repeated surgery entails a higher rate of complications.

PMID- 29454468
TI  - Systematic review, meta-analysis, and a high-volume center experience supporting
      the new role of mural nodules proposed by the updated 2017 international
      guidelines on IPMN of the pancreas.
AB  - BACKGROUND: Mural nodules (MNs) have a predominant role in the 2016 revision of
      the international guidelines on intraductal papillary mucinous neoplasms (IPMN)
      of the pancreas. The aim of this study was to evaluate MNs as predictors of
      invasive cancer (iCa) or high-grade dysplasia (HGD) in IPMNs and to investigate
      the role of MN size in risk prediction. METHODS: A PRISMA-compliant systematic
      review of the literature and meta-analysis on selected studies were conducted.
      The random effect model was adopted, and the pooled SMD (standardized mean
      difference) obtained. The surgical series of IPMNs at a single high-volume
      institution was reviewed. RESULTS: This review included 70 studies and 2297
      resected IPMNs. MNs have a positive predictive value for malignancy of 62.2%. The
      meta-analysis suggested that MN size has a considerable effect on predicting
      IPMNs with both iCa or HGD with a mean SMD of 0.79. All studies included in the
      meta-analysis used contrast-enhanced endosonography (CE-EUS) to assess MNs. Due
      to the heterogeneity of the proposed thresholds, no reliable MN size cut-off was
      identified. Of 317 IPMNs resected at our institution, 102 (32.1%) had a
      preoperative diagnosis of MN. Multivariate analysis showed that MN is the only
      independent predictor of iCa and HGD for all types of IPMNs. CONCLUSION: MNs are
      reliable predictors of iCa and HGD in IPMNs as proposed by the 2016 IAP
      guidelines. CE-EUS seems to be the best tool for characterizing size and has the
      best accuracy for predicting malignancy. Further studies should determine
      potential MN dimensional cut-offs.

PMID- 29454469
TI  - Use of a phoneme monitoring task to examine lexical access in adults who do and
      do not stutter.
AB  - Previous work has postulated that a deficit in lexicalization may be an
      underlying cause of a stuttering disorder (Prins, Main, & Wampler, 1997; Wingate,
      1988). This study investigates the time course of lexicalization of nouns and
      verbs in adults who stutter. A generalized phoneme monitoring (PM) paradigm was
      used. Adults who stutter (AWS) and typically-fluent peers both showed an expected
      effect of word class (verbs yielded slower and less accurate monitoring than
      nouns), as well as phoneme position (word medial/final phonemes yielded slower
      and less accurate monitoring than word initial phonemes). However, AWS had
      considerably more difficulty when targets to be monitored were embedded in the
      medial position. A negative correlation between speed and accuracy was found in
      typically fluent adults, but not in AWS. AWS also scored nonsignificantly more
      poorly on an experimental language task. Because of the additional difficulty
      noted in AWS with word-medial targets, our results provide evidence of
      phonological encoding differences between the two groups. Expanded use of the PM
      paradigm is recommended for the exploration of additional aspects of language
      processing in people who stutter.

PMID- 29454470
TI  - Intracerebral electroencephalography in targeting anterior thalamic nucleus for
      deep brain stimulation in refractory epilepsy.
AB  - BACKGROUND: Results of DBS of ATN in refractory epilepsy depend on accuracy of
      the electrode's location. We searched for characteristic intraoperative,
      intracerebral EEG recording pattern from anterior thalamic nuclei (ATNs) as a
      biological marker for verifying the electrode's position. METHODS: There were six
      patients with refractory epilepsy scheduled for deep brain stimulation (DBS)
      procedure. At surgery, to map the target, we recorded EEG from each lead of DBS
      electrodes. One patient underwent a 24 hours EEG with continuous recording from
      both ATNs before internalization of stimulator units. RESULTS: In all patients we
      recorded spontaneous bioelectric activity of ATNs. The pattern of the recording
      from the ATN was similar in all cases. In the one patient where 24-hour recording
      was done with simultaneous scalp EEG, a complex partial seizure was captured.
      CONCLUSION: This is the first report of using DBS electrode for intraoperative
      EEG recordings from the ATN in patients with refractory epilepsy. Since we
      managed to find the characteristic pattern of bioelectric activity of ATN, this
      technique seems to be a promising method for targeting this structure during the
      operation.

PMID- 29454471
TI  - Severe course of neuromyelitis optica in a female patient with chronic C
      hepatitis.
AB  - Neuromyelitis optica (NMO) is a rare, disabling, recurring inflammatory
      demyelinating disease affecting the spinal cord and optic nerves with
      predominance in women. We present the case of a female patient with chronic C
      hepatitis, who, despite treatment, developed severe symptoms of NMO during
      pregnancy and postpartum.

PMID- 29454472
TI  - Re: Lee C. Zhao, Aaron C. Weinberg, Ziho Lee, et al. Robotic Ureteral
      Reconstruction Using Buccal Mucosa Grafts: A Multi-institutional Experience. Eur
      Urol 2018;73:419-26: Robotic Ureteral Reconstruction with Buccal Mucosal Graft: A
      Call Not To Lose Momentum.

PMID- 29454473
TI  - Re: Propensity Score Analysis of Radical Cystectomy Versus Bladder-sparing
      Trimodal Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic.

PMID- 29454474
TI  - Cardiovascular, pulmonary, and metabolic toxicities complicating tyrosine kinase
      inhibitor therapy in chronic myeloid leukemia: Strategies for monitoring,
      detecting, and managing.
AB  - Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, the incidence of
      which increases with age. Tyrosine kinase inhibitors (TKIs) are the mainstay of
      CML treatment, including imatinib, nilotinib, dasatinib, bosutinib, and
      ponatinib. Beyond matching patient disease profiles with TKI specificity,
      differences in the efficacy and toxicity profiles and a patient's comorbid risk
      factors should be considered when selecting the most appropriate agent. Our
      objectives are to review the incidence and severity of cardiovascular, metabolic,
      and pulmonary disorders associated with these TKIs, highlighting differences in
      adverse event profiles, suggested risk-mitigation strategies, and guidance for
      TKI selection in different settings. Patients receiving TKI agents for CML should
      be monitored for signs and symptoms of toxicity throughout therapy. Preemptive
      assessment, early toxicity recognition, and prompt management of cardiovascular,
      metabolic, and pulmonary toxicities can minimize treatment-limiting complications
      and improve outcomes in patients with CML.

PMID- 29454475
TI  - Does childhood neglect contribute to violent behavior in adulthood? A review of
      possible links.
AB  - Child neglect, whether intentional or unintentional on the part of caregivers,
      has serious and far-reaching negative consequences for children. Neglect is the
      most prevalent form of child maltreatment and has been associated with impaired
      cognitive development, changes in brain structure and nervous systems, behavioral
      and personality disorders and poor academic performance. However, the role of
      child neglect, and subtypes of neglect, in the development of adult violent
      behavior is not well understood. The "cycle of violence" hypothesis, which
      predicts that individuals exposed to child physical abuse are more likely to be
      physically violent in adulthood, is well supported by the literature. However, a
      growing number of studies suggests that child neglect may be equally predictive,
      or more predictive, of adult violent behavior than child physical abuse. The
      present review considers a range of studies that investigate aspects of this
      relationship, and identifies key patterns and trends that have emerged from these
      investigations. Methodological issues and limitations of the existing literature
      are also identified and new research directions suggested. This review also
      considers studies that support the possibility of protective factors against the
      development of adult violent behavior in victims of child neglect.

PMID- 29454476
TI  - Frequency of Electrocardiographic Abnormalities in Patients With Psoriasis.
AB  - Psoriasis is a chronic inflammatory disease associated with cardiovascular
      disease, for example, myocardial infarction, stroke, cardiovascular death, and
      arrhythmias. The resting electrocardiogram may carry prognostic information, but
      limited evidence is available of electrocardiographic findings in subjects with
      psoriasis. The electrocardiographic results were compared between 1,131 subjects
      with self-reported psoriasis and 18,397 controls participating in the Danish
      General Suburban Population Study (GESUS). The mean heart rate was marginally
      increased in patients with psoriasis (66 +/- 11 vs 65 +/- 11 beats/min, p =
      0.007), but not after adjustment for smoking and body mass index. All other
      examined electrocardiographic variables, including QT interval corrected for
      heart rate with the Fridericia formula, PR interval, QRS duration, R axis, P-wave
      duration in lead V1, P-terminal force, J point elevation in lead V1,
      electrocardiographic criteria for left ventricular hypertrophy,
      electrocardiographic signs of previous myocardial infarction, and premature
      ventricular or supraventricular complexes, respectively, were comparable between
      the 2 groups. In conclusion, psoriasis was associated with a marginal increase in
      resting heart rate, which was driven by smoking and increased body mass index.
      All other examined electrocardiographic variables were similar between the 2
      groups. The results suggest that psoriasis per se is not associated with
      significant abnormalities of the electrocardiogram.

PMID- 29454477
TI  - Effect of Elevated C-Reactive Protein Level at Discharge on Long-Term Outcome in
      Patients Hospitalized for Acute Heart Failure.
AB  - In the acute heart failure (AHF) setting, the usefulness of C-reactive protein
      (CRP) at admission as a risk marker is challenged by the possible confounding
      effect of an acute-phase response. We thus evaluated the relation of CRP level at
      discharge (i.e., after stabilization of AHF) with subsequent postdischarge
      outcome in patients hospitalized for AHF. The acute decompensated heart failure
      syndromes study prospectively registered 4,269 hospitalized AHF patients with
      data on CRP levels at discharge. The median CRP level was 3.1 mg/L (interquartile
      range 1.1 to 9.5 mg/L). Within 120 days after discharge, only CRP levels in the
      fourth quartile (>=9.6 mg/L) were independently associated with higher all-cause
      mortality (adjusted hazard ratio [HR], 1.68) according to multivariable models
      with first-quartile (<=1.1 mg/L) as the reference. However, the HR for CRP levels
      in the fourth quartile decreased markedly with time, and CRP levels in the second
      (1.2 to 3.1 mg/L) and third (3.2 to 9.5 mg/L) quartiles were independently
      associated with poorer survival after the 120-day follow-up period (adjusted HR,
      1.41 and 1.63, respectively). In addition, only CRP levels in the third quartile
      were independently associated with the composite end point of all-cause death and
      readmission for AHF after the 120 days of long-term follow-up (adjusted HR,
      1.31). In conclusion, our results suggest that a modestly elevated CRP level
      (approximately 3 to 10 mg/L) at discharge had unique long-term prognostic
      implications in hospitalized patients with AHF.

PMID- 29454478
TI  - Usefulness of Integrating Heart Failure Risk Factors Into Impairment of Global
      Longitudinal Strain to Predict Anthracycline-Related Cardiac Dysfunction.
AB  - The prediction of cancer therapeutics-related cardiac dysfunction (CTRCD) is an
      essential aspect of care for individuals who receive potentially cardiotoxic
      oncologic treatments. Certain clinical risk factors have been described for
      incident CTRCD, and measurement of left ventricular (LV) longitudinal strain by
      speckle tracking 2-dimensional echocardiography (2DE) is the best-validated
      myocardial mechanical imaging assessment to detect subtle changes in LV function
      during cancer treatment. However, the direct integration of clinical and imaging
      risk factors to predict CTRCD has not yet been extensively examined. This was a
      retrospective study of 183 women with breast cancer aged 50.9 +/- 10.8 years who
      received treatment with anthracyclines (doxorubicin dose of 422 +/- 69 mg/m2,
      with 41.2% of subjects also receiving trastuzumab) and underwent 2DE at
      clinically determined intervals. CTRCD was diagnosed when LV ejection fraction
      dropped >=10% to a subnormal (<53%) value by 2DE. Left ventricular global
      longitudinal strain (LV-GLS) was assessed offline. The risk prediction tool based
      only on clinical factors previously described by Ezaz et al was applied to our
      cohort and accurately stratified these subjects into low-, intermediate-, and
      high-risk groups, with incident CTRCD in 7.4%, 26.9%, and 54.6%, respectively
      (chi-square = 20.7, p <0.0001). We developed novel multivariate models to predict
      CTRCD using (1) demographic variables only (c = 0.8674), (2) echocardiographic
      (peak LV-GLS) variables only (c = 0.8440), or (3) a combination of demographic
      and echocardiographic variables, with the combined model exhibiting superior
      receiver-operating characteristics (c = 0.9629). In conclusion, estimation of
      CTRCD risk should integrate all available data, including both clinical variables
      and an imaging assessment.

PMID- 29454479
TI  - The role of antibiotics in acute uncomplicated diverticulitis: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Antibiotics use in acute uncomplicated diverticulitis (AUD) remains
      debated despite recent studies suggesting no difference in outcomes for patients
      treated without antibiotics. DATA SOURCES: Systematic review and meta-analysis
      were performed to determine the role of antibiotics in managing AUD. Literature
      search was conducted using Medline, EMBASE, Scopus, the Cochrane Library, and Web
      of Science databases from 1946 to June 2017. Eight studies with 2469 patients
      were included for review. Overall complication rates were not statistically
      significant between groups (OR 0.72; CI 0.45 to 1.16; P = 0.18), but antibiotic
      use was associated with a longer length of stay in hospital. Subgroup analysis
      revealed no difference in readmission rates, treatment failure rates, progression
      to complicated diverticulitis, or increased need for elective or emergent surgery
      between study groups. CONCLUSIONS: Antibiotic use in patients with AUD increases
      length of hospital stay but is not associated with a reduction in overall or
      individual complication rates.

PMID- 29454480
TI  - Preoperative pain measures ineffective in outpatient abdominal surgeries.
AB  - BACKGROUND: The multimodality addition of preoperative gabapentin, acetaminophen,
      and celecoxib (GAC) and postoperative TENS has been recommended to diminish
      narcotics. We predict that GAC-TENS implementation will reduce recovery room
      time, improve pain control, reduce narcotic refills, and demonstrate usefulness
      of TENS treatment. METHODS: A prospective study compared a control group of
      patients not utilizing the GAC-TENS protocol during 2015 to patients using the
      GAC-TENS protocol during 2016. RESULTS: There was less recovery room time in the
      control group compared to the protocol group. Postoperative day one pain control
      was similar between the groups. Less refills were noted. TENS unit satisfaction
      level was rated "very helpful" by 63% of patients. CONCLUSION: The results call
      into question the efficacy of the American Pain Society recommendations as they
      increase time in recovery room but do not decrease the quantity of narcotics used
      in the recovery room, nor do they improve pain satisfaction responses.

PMID- 29454481
TI  - Getting out of the comfort zone with point-of-care ultrasound.

PMID- 29454482
TI  - Surgery for metastases not of colorectal, neuroendocrine, sarcomatous, or ovarian
      (NCNSO) origin: The cornerstone but not the only stone.

PMID- 29454484
TI  - Shortening antibiotic duration for community acquired pneumonia.

PMID- 29454483
TI  - Postoperative opioid prescribing: Getting it RIGHTT.
AB  - BACKGROUND: Prescription opioid medications account for a large number of fatal
      and non-fatal overdoses. Many opioid prescription medications after surgery go
      unused, with the potential for diversion and misuse. As surgeons become
      increasingly aware of their role in opioid misuse, better tools are needed to
      guide behavior. DATA SOURCES: There has recently been a plethora of research into
      opioid prescribing after surgery. A review of this literature was performed using
      a search for manuscripts written in the English language. Our goal was to develop
      an easily recalled approach to postoperative opioid prescribing. RESULTS: Based
      on an extensive review of recent literature, we developed the acronym RIGHTT:
      Risk for adverse event, Insight into pain, Going over pain plan, Halting opioids,
      Tossing unused opioids and Trouble identification. It is important that surgeons
      recognize the potential for opioid misuse in their patients. Strategies have been
      developed to decrease the risk of prescribing opioids. RIGHTT provides a simple
      acronym for surgeons to integrate best-practice strategies into their management
      of post-surgical opioids.

PMID- 29454486
TI  - Discussion.

PMID- 29454485
TI  - What is the ideal conduit or technique for reconstruction of the right
      ventricular outflow tract?

PMID- 29454487
TI  - A cost-utility analysis of transcatheter versus surgical aortic valve replacement
      for the treatment of aortic stenosis in the population with intermediate surgical
      risk.
AB  - OBJECTIVE: Although transcatheter aortic valve implantation has been shown to be
      noninferior to surgical aortic valve replacement in patients with severe aortic
      stenosis at intermediate surgical risk, the cost-effectiveness of this strategy
      in this population is unknown. Our objective was to conduct a cost-utility
      analysis comparing transcatheter aortic valve implantation with surgical aortic
      valve replacement in the population with intermediate risk severe aortic
      stenosis. METHODS: A fully probabilistic Markov model with 30-day cycles was
      constructed from the Canadian third-party payer's perspective to estimate the
      difference in cost and effectiveness (measured as quality-adjusted life years) of
      transcatheter aortic valve implantation versus surgical aortic valve replacement
      for intermediate-risk patients over a lifetime time horizon, discounted at 1.5%
      per annum. Clinical trial data from The Placement of Aortic Transcatheter Valve 2
      informed the efficacy inputs. Costs (adjusted to 2016 Canadian dollars) were
      obtained from the Canadian Institute of Health Information and the Ontario
      Schedule of Benefits. Incremental cost-effectiveness ratios were calculated.
      RESULTS: In the base-case analysis, total lifetime costs for transcatheter aortic
      valve implantation were $10,548 higher than surgical aortic valve replacement but
      added 0.23 quality-adjusted life years, for an incremental cost-effectiveness
      ratio of $46,083/quality-adjusted life-years gained. Deterministic 1-way analyses
      showed that the incremental cost-effectiveness ratio was sensitive to rates of
      complications and cost of the transcatheter aortic valve implantation prosthesis.
      There was moderate-to-high parameter uncertainty; transcatheter aortic valve
      implantation was the preferred option in only 52.7% and 55.4% of the simulations
      at a $50,000 and $100,000 per quality-adjusted life years willingness-to-pay
      thresholds, respectively. CONCLUSIONS: On the basis of current evidence,
      transcatheter aortic valve implantation may be cost-effective for the treatment
      of severe aortic stenosis in patients with intermediate surgical risk. There
      remains moderate-to-high uncertainty surrounding the base-case incremental cost
      effectiveness ratio.

PMID- 29454488
TI  - Robust fault detection for the dynamics of high-speed train with multi-source
      finite frequency interference.
AB  - This paper proposes a composite fault detection scheme for the dynamics of high
      speed train (HST), using an unknown input observer-like (UIO-like) fault
      detection filter, in the presence of wind gust and operating noises which are
      modeled as disturbance generated by exogenous system and unknown multi-source
      disturbance within finite frequency domain. Using system input and system output
      measurements, the fault detection filter is designed to generate the needed
      residual signals. In order to decouple disturbance from residual signals without
      truncating the influence of faults, this paper proposes a method to partition the
      disturbance into two parts. One subset of the disturbance does not appear in
      residual dynamics, and the influence of the other subset is constrained by
      Hinfinity performance index in a finite frequency domain. A set of detection
      subspaces are defined, and every different fault is assigned to its own detection
      subspace to guarantee the residual signals are diagonally affected promptly by
      the faults. Simulations are conducted to demonstrate the effectiveness and merits
      of the proposed method.

PMID- 29454489
TI  - Basal cell nevus syndrome (Gorlin syndrome): genetic insights, diagnostic
      challenges, and unmet milestones.
AB  - In this article, we present three clinical case reports on Basal Cell Nevus
      Syndrome (Gorlin Syndrome). Gorlin syndrome is an inherited medical condition
      with challenges that manifest in multiple body systems and complicate early
      diagnosis. We examine the epidemiology of the disease and benefits of genetic
      testing, molecular pathophysiology, and advancement in the molecular-based
      therapy of Basal Cell Nevus syndrome. The goal of this paper is to shed light on
      both unmet challenges and advancements in the management of Gorlin syndrome and
      to provide a new clinical perspective and guidance for future research.
      Furthermore, the FDA approved Hedgehog pathway inhibitors Vismodegib and
      Sonidegib designed for advanced basal cell carcinoma have opened a new door for
      treatment that may ultimately decrease the number of surgeries for a patient with
      Gorlin syndrome. The role of these agents in syndromic odontogenic keratocyst has
      not been studied extensively, but one study found that hedgehog pathway
      inhibitors decrease the size of syndromic odontogenic keratocyst. Ideal surgical
      treatment that balances low recurrence rates with low impact on one's quality of
      life for syndromic odontogenic keratocyst is another unanswered question for oral
      and maxillofacial surgeons. Per survey studies, treatment options practiced for
      syndromic odontogenic keratocyst range from marsupialization to segmental
      osteotomy. Future studies performed should take a comprehensive long-term
      approach with at least three years of follow-up in order to determine the most
      appropriate treatment.

PMID- 29454490
TI  - Subchronic exposure to acrylamide leads to pancreatic islet remodeling determined
      by alpha cell expansion and beta cell mass reduction in adult rats.
AB  - Acrylamide (AA) is a toxic substance, used to synthesize polymers for industrial
      and laboratory processes. Also, AA is a food contaminant formed during the high
      temperature preparation of carbohydrate-rich food. The main subject of this study
      was to examine effects of subchronic AA treatment on the islets of Langerhans of
      adult rats. Adult male Wistar rats were orally treated with 25 or 50 mg/kg bw of
      AA for 3 weeks. Qualitative and quantitative immunohistochemical evaluation of
      glucagon and insulin expression and stereological analyses of pancreatic alpha
      and beta cells were performed. Serum insulin and glucose levels were measured.
      Analysis of glucagon-immunostained sections revealed a dose-dependent increase of
      intensity of glucagon immunopositive signal, alpha cell surface and numerical
      densities, volume density of alpha cell nuclei and nucleocytoplasmic ratio in AA
      treated groups compared to the control. In insulin-immunolabeled pancreatic
      sections in AA-treated animals was observed decrease of intensity of insulin
      immunopositive signal, beta cell surface, numerical and volume densities and
      volume density of beta cell cytoplasm. Serum insulin and glucose concentrations
      remained unchanged after both AA treatments. The number of islets of Langerhans
      was not affected by AA treatment. Our results suggest that AA subchronic
      treatment of adult rats leads to remodeling of islet of Langerhans characterized
      by alpha cell expansion and beta cell mass reduction.

PMID- 29454491
TI  - Risk assessment for ballast water management - Learning from the Adriatic Sea
      case study.
AB  - The ballast water management convention incorporates principles of risk
      assessment. A new ballast water management risk assessment model was developed to
      support the implementation of most efficient management measures, which we also
      present as a flowchart decision support system model. The risk assessment model
      was tested using data from port baseline surveys where available, and real
      shipping and ballast water discharges data. The here presented ballast water
      management risk assessment and possible management options are applicable
      elsewhere to support and improve complex decision making in the implementation of
      management requirements according to the ballast water management convention. If
      needed, the model may easy be adapted to address local specifics in any other
      region or area.

PMID- 29454492
TI  - Potential transfer of aquatic organisms via ballast water with a particular focus
      on harmful and non-indigenous species: A survey from Adriatic ports.
AB  - Ballast water discharges may cause negative impacts to aquatic ecosystems, human
      health and economic activities by the introduction of potentially harmful
      species. Fifty untreated ballast water tanks, ten in each port, were sampled in
      four Adriatic Italian ports and one Slovenian port. Salinity, temperature and
      fluorescence were measured on board. Faecal indicator bacteria (FIB), phyto- and
      zooplankton were qualitatively and quantitatively determined to identify the
      species assemblage arriving in ballast water. FIB exceeded the convention
      standard limits in 12% of the sampled tanks. Vibrio cholerae was not detected.
      The number of viable organisms in the size groups (minimum dimension) <50 and
      >=10 MUm and >=50 MUm resulted above the abundances required from the Ballast
      Water Management Convention in 55 and 86% of the samples, respectively. This is
      not surprising as unmanaged ballast waters were sampled. Some potentially toxic
      and non-indigenous species were observed in both phyto- and zooplankton
      assemblages.

PMID- 29454493
TI  - Updating the recommendations for treatment of tardive syndromes: A systematic
      review of new evidence and practical treatment algorithm.
AB  - BACKGROUND: Management of tardive syndromes (TS) is challenging, with only a few
      evidence-based therapeutic algorithms reported in the American Academy of
      Neurology (AAN) guideline in 2013. OBJECTIVE: To update the evidence-based
      recommendations and provide a practical treatment algorithm for management of TS
      by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents
      (DRBAs) an effective TS treatment? 2) Does switching from typical to atypical
      DRBAs reduce TS symptoms? 3) What is the efficacy of pharmacologic agents in
      treating TS? 4) Do patients with TS benefit from chemodenervation with botulinum
      toxin? 5) Do patients with TS benefit from surgical therapy? METHODS: Systematic
      reviews were conducted by searching PsycINFO, Ovid MEDLINE, PubMed, EMBASE, Web
      of Science and Cochrane for articles published between 2012 and 2017 to identify
      new evidence published after the 2013 AAN guidelines. Articles were classified
      according to an AAN 4-tiered evidence-rating scheme. To the extent possible, for
      each study we attempted to categorize results based on the description of the
      population enrolled (tardive dyskinesia [TD], tardive dystonia, tardive tremor,
      etc.). Recommendations were based on the evidence. RESULTS AND RECOMMENDATIONS:
      New evidence was combined with the existing guideline evidence to inform our
      recommendations. Deutetrabenazine and valbenazine are established as effective
      treatments of TD (Level A) and must be recommended as treatment. Clonazepam and
      Ginkgo biloba probably improve TD (Level B) and should be considered as
      treatment. Amantadine and tetrabenazine might be considered as TD treatment
      (Level C). Pallidal deep brain stimulation possibly improves TD and might be
      considered as a treatment for intractable TD (Level C). There is insufficient
      evidence to support or refute TS treatment by withdrawing causative agents or
      switching from typical to atypical DRBA (Level U).

PMID- 29454494
TI  - Historical perspectives on tardive dyskinesia.
AB  - Tardive dyskinesia (TD) is a persistent hyperkinetic movement disorder associated
      with dopamine receptor blocking agents including antipsychotic medications.
      Although uncertainty and concern about this drug side effect have vacillated
      since its initial recognition 60 years ago, recent commercial interest in
      developing effective treatments has rekindled scientific and clinical interest
      after a protracted period of neglect. Although substantial research has advanced
      knowledge of the clinical features and epidemiology of TD, many fundamental
      questions raised by early investigators remain unresolved. In this paper, we
      review the early clinical reports that led to the acceptance of TD as an
      iatrogenic disorder and the lingering controversies that emerged thereafter.
      Continued research on TD as a serious adverse reaction to treatment may not only
      enhance patient outcomes and recovery efforts but may also provide insights into
      both the mechanism of action of antipsychotic drugs and the nosology and
      pathophysiology of idiopathic psychomotor disorders.

PMID- 29454495
TI  - Three-dimensional digital imaging to assess newborn biparietal diameter at term.

PMID- 29454496
TI  - Heterologous expression of mlrA in a photoautotrophic host - Engineering
      cyanobacteria to degrade microcystins.
AB  - In this report, we establish proof-of-principle demonstrating for the first time
      genetic engineering of a photoautotrophic microorganism for bioremediation of
      naturally occurring cyanotoxins. In model cyanobacterium Synechocystis sp. PCC
      6803 we have heterologously expressed Sphingopyxis sp. USTB-05 microcystinase
      (MlrA) bearing a 23 amino acid N-terminus secretion peptide from native
      Synechocystis sp. PCC 6803 PilA (sll1694). The resultant whole cell biocatalyst
      displayed about 3 times higher activity against microcystin-LR compared to a
      native MlrA host (Sphingomonas sp. ACM 3962), normalized for optical density. In
      addition, MlrA activity was found to be almost entirely located in the
      cyanobacterial cytosolic fraction, despite the presence of the secretion tag,
      with crude cellular extracts showing MlrA activity comparable to extracts from
      MlrA expressing E. coli. Furthermore, despite approximately 9.4-fold higher
      initial MlrA activity of a whole cell E. coli biocatalyst, utilization of a
      photoautotrophic chassis resulted in prolonged stability of MlrA activity when
      cultured under semi-natural conditions (using lake water), with the heterologous
      MlrA biocatalytic activity of the E. coli culture disappearing after 4 days,
      while the cyanobacterial host displayed activity (3% of initial activity) after 9
      days. In addition, the cyanobacterial cell density was maintained over the
      duration of this experiment while the cell density of the E. coli culture rapidly
      declined. Lastly, failure to establish a stable cyanobacterial isolate expressing
      native MlrA (without the N-terminus tag) via the strong cpcB560 promoter draws
      attention to the use of peptide tags to positively modulate expression of
      potentially toxic proteins.

PMID- 29454497
TI  - Uptake of nicotine from discarded cigarette butts - A so far unconsidered path of
      contamination of plant-derived commodities.
AB  - This study aimed to elucidate the origin of the widespread nicotine contamination
      of plant-derived commodities, by conducting field experiments with various herbs
      and spice plants. By scattering tobacco and cigarette butts on the field and
      subsequent nicotine analyses of the acceptor plants, we verified that the
      alkaloid is leached out into the soil and is taken up by the crop plants. This
      path of contamination pertains even when there is only one cigarette butt per
      square meter. Even such minor pollution results - at least in the case of basil
      and peppermint - in considerable high nicotine contaminations, which exceed the
      maximum residue level by more than 20-fold. The data reported here clearly
      outline the large practical relevance of this soil-borne contamination path and
      imply that unthoughtful disposal of cigarette butts in the field by farm workers
      may be the reason for the widespread occurrence of nicotine contamination in
      plant-derived commodities. Therefore, such misbehavior needs to be prevented
      using education and sensitization, and by including this issue into the
      guidelines of good agricultural practice.

PMID- 29454498
TI  - [Maintenance of exclusive breastfeeding after three months postpartum: An
      experience in a health department of a Valencian Community].
AB  - AIMS: To investigate the prevalence of EBF at 3-months postpartum, and the early
      factors for discontinuation. DESIGN: Observational, retrospective study.
      LOCATION: Health department of La Ribera, Valencia, Spain. PARTICIPANTS: Newborns
      between December 2012 to January 2017. METHODS: Pregnant women were interviewed
      at postpartum and at 3 months regarding variables associated with breastfeeding
      initiation and continuation, matched with socio-demographic and obstetric
      neonatal information. MAIN MEASUREMENTS: Prevalence of breastfeeding at discharge
      and exclusive breastfeeding at 3 months. Reasons for interrupt exclusive
      breastfeeding. Chi-square determination between qualitative variables. FINDINGS:
      One thousand three hundred and thirty-eighth women were recruited. EBF at
      discharge was 68.2% (913) and at 3 months 46.7% (625). EBF duration was 68.7+/
      32.7 days (95% CI: 66.9-71.2). We found statistically significant differences
      between the type of breastfeeding and the variables, year of study, country of
      origin and parity (P<0.001, P=0.005 and P=0.05 respectively). Hypogalactia
      (21.8%) and lower than recommended increase in newborn weight gain (14.9%) were
      most frequent factors for discontinuation. CONCLUSION: The prevalence of EBF at 3
      months is low compared to other similar studies, although we see an upward trend.
      Belief in hypogalactia influenced the maintenance of exclusive breastfeeding.

PMID- 29454499
TI  - Comment to "Preoperative sarcopenia determinants in pancreatic cancer patients".

PMID- 29454500
TI  - Making body composition measurement a part of routine care in children.

PMID- 29454501
TI  - Postoperative inflammation and insulin resistance in relation to body
      composition, adiposity and carbohydrate treatment: A randomised controlled study.
AB  - BACKGROUND & AIMS: The aims of this study were to identify whether differences in
      distribution of adipose tissue and skeletal muscle in obese and non-obese
      individuals contribute to the magnitude of the postoperative inflammatory
      response and insulin resistance, with and without preoperative treatment with
      carbohydrate drinks. METHODS: Thirty-two adults (16 obese/16 non-obese)
      undergoing elective major open abdominal surgery participated in this 2 * 2
      factorial, randomised, double-blind, placebo-controlled study. Participants
      received Nutricia preOp(r) or placebo (800 ml on the night before surgery/400 ml
      2-3 h preoperatively) after stratifying for obesity. Insulin sensitivity was
      measured using the hyperinsulinaemic-euglycaemic clamp preoperatively and on the
      1st postoperative day. Vastus lateralis, omental and subcutaneous fat biopsies
      were taken pre- and postoperatively and analysed after RNA extraction. The
      primary endpoint was within subject differences in insulin sensitivity. RESULTS:
      Major abdominal surgery was associated with a 42% reduction in insulin
      sensitivity from mean(SD) M value of 37.3(11.8) MUmol kg-1 fat free mass (FFM) to
      21.7(7.4) MUmol kg-1 FFM, but this was not influenced by obesity or preoperative
      carbohydrate treatment. Activation of the triggering receptor expressed on
      myeloid cells (TREM1) pathway was seen in response to surgery in omental fat
      samples. In postoperative muscle samples, gene expression differences indicated
      activation of the peroxisome proliferator-activated receptor (PPAR
      alpha)/retinoid X-receptor (RXR-alpha) pathway in obese but not in non-obese
      participants. There were no significant changes in gene expression pathways
      associated with carbohydrate treatment. CONCLUSION: The reduction in insulin
      sensitivity associated with major abdominal surgery was confirmed but there were
      no differences associated with preoperative carbohydrates or obesity.

PMID- 29454502
TI  - Prevalence and side effects of pediatric home tube feeding.
AB  - BACKGROUND & AIMS: Tube feeding ensures growth, but can have negative effects on
      health and psychosocial functioning, resulting in health related costs. The aims
      of this study were to determine the prevalence of pediatric home tube feeding in
      the Netherlands and to assess the clinical characteristics of tube fed children
      and side effects of tube feeding. METHODS: The prevalence of pediatric home tube
      feeding was calculated using data (2010-2014) of both the Medicines and Devices
      Information Project of the National Health Care Institute, and Statistics
      Netherlands. Subsequently, a cross-sectional parental online questionnaire was
      used to obtain data regarding clinical characteristics of tube fed children and
      side effects of tube feeding. Children aged <=17 years receiving tube feeding >=2
      weeks were included. RESULTS: The prevalence of pediatric home tube feeding was
      83-92:100,000 children/year. Parents of 279 children (53% boys) completed the
      questionnaire. Most children (88%) had >=1 medical diagnosis, of which congenital
      abnormalities (42%), perinatal problems (38%) and neurologic diseases (16%) were
      most common. They had gastrostomy (60%), nasogastric (33%), or other tube types
      (7%). Parents of most children (74%) mentioned >=1 side effect due to tube
      feeding. Vomiting (37%), lack of appetite (29%), and gagging (29%) were reported
      most frequently. Nasogastric tube placement resolved in negative experiences
      (94%). CONCLUSIONS: The prevalence of pediatric home tube feeding varies between
      83 and 92:100,000 children/year in the Netherlands. These children are
      characterized by various underlying medical diagnoses. Side effects of tube
      feeding are frequently reported by parents. Further studies should focus on
      methods reducing side effects.

PMID- 29454503
TI  - A mechanistic look at sacubitril/valsartan action. Unravelling magician's
      secrets.

PMID- 29454504
TI  - The Radiobiology of Proton Therapy: Challenges and Opportunities Around Relative
      Biological Effectiveness.
AB  - With the current UK expansion of proton therapy there is a great opportunity for
      clinical oncologists to develop a translational interest in the associated
      scientific base and clinical results. In particular, the underpinning controversy
      regarding the conversion of photon dose to proton dose by the relative biological
      effectiveness (RBE) must be understood, including its important implications. At
      the present time, the proton prescribed dose includes an RBE of 1.1 regardless of
      tissue, tumour and dose fractionation. A body of data has emerged against this
      pragmatic approach, including a critique of the existing evidence base, due to
      choice of dose, use of only acute-reacting in vivo assays, analysis methods and
      the reference radiations used to determine the RBE. Modelling systems, based on
      the best available scientific evidence, and which include the clinically useful
      biological effective dose (BED) concept, have also been developed to estimate
      proton RBEs for different dose and linear energy transfer (LET) values. The
      latter reflect ionisation density, which progressively increases along each
      proton track. Late-reacting tissues, such as the brain, where alpha/beta = 2 Gy,
      show a higher RBE than 1.1 at a low dose per fraction (1.2-1.8 Gy) at LET values
      used to cover conventional target volumes and can be much higher. RBE changes
      with tissue depth seem to vary depending on the method of beam delivery used. To
      reduce unexpected toxicity, which does occasionally follow proton therapy, a more
      rational approach to RBE allocation, using a variable RBE that depends on dose
      per fraction and the tissue and tumour radiobiological characteristics such as
      alpha/beta, is proposed.

PMID- 29454505
TI  - Current Management of Intracranial Germ Cell Tumours.
AB  - Intracranial germ cell tumours (icGCTs) are uncommon tumours occurring in
      children and young adults. They are usually segregated into germinomas and non
      germinomatous tumours (NGGCTs) in most classifications. Germinomas are highly
      curable tumours with multimodality treatment, but NGGCTs are associated with
      poorer survival outcomes. There are some differences in the approach to the
      management of icGCTs globally. Current research generally focuses on reducing
      treatment intensity, particularly the dose and volume of radiotherapy, in order
      to minimise the risks of late sequelae while maintaining high cure rates in
      icGCTs.

PMID- 29454506
TI  - Becoming a Team: The Nature of the Parent-Healthcare Provider Relationship when a
      Child is Dying in the Pediatric Intensive Care Unit.
AB  - PURPOSE: To explore bereaved parents' perspectives of parent and staff roles in
      the pediatric intensive care unit when their child was dying, and their
      relationships with healthcare staff during this time. DESIGN AND METHODS:
      Constructivist grounded theory was used to undertake this study. Semi-structured
      interviewers were conducted with 26 bereaved parents recruited from four
      Australian pediatric intensive care units. The constant comparative method,
      coupled with open, focused, and theoretical coding were used for data analysis.
      RESULTS: Becoming a team explores the changes that occurred to the parent
      healthcare provider relationship when parents realized their child was dying and
      attempted to become part of their child's care team. When the focus of care
      changed from 'life-saving' to 'end-of-life', parents' perspectives and desires of
      their and the healthcare providers' roles changed. Parents' attempted to
      reconstruct their roles to match their changing perspectives, which may or may
      not have been successful, depending on their ability to successfully negotiate
      these roles with healthcare providers. CONCLUSIONS: Findings offer insights into
      parental understandings of both the parental and healthcare provider roles for
      parents of dying children in intensive care, and the ways in which the parent
      healthcare provider relationships can influence and be influenced by changes to
      these roles. PRACTICE IMPLICATIONS: Successful parent-healthcare provider
      relationships require an understanding of the parental and healthcare provider
      role from the parents' perspective. The meanings of the parental and healthcare
      provider roles should be explored with parents of dying children, and supported
      as much as possible to enable the development of a collaborative relationship.

PMID- 29454507
TI  - Pediatric Early Warning Score Systems, Nurses Perspective - A Focus Group Study.
AB  - PURPOSE: Pediatric early warning score (PEWS) systems are used to monitor
      pediatric patients' vital signs and facilitate the treatment of patients at risk
      of deteriorating. The aim of this study was to gain knowledge about nurses'
      experiences with PEWS and to highlight factors facilitating and impeding the use
      of PEWS tools in clinical practice. DESIGN AND METHODS: An exploratory
      qualitative design was chosen using focus group interviews to gain a deeper
      understanding of nurses' experiences with PEWS. A total of five focus group
      interviews were conducted at three hospitals, and a qualitative meaning
      condensation analysis as described by Kvale and Brinkmann was performed. RESULTS:
      Seven themes were identified, including i) lack of interdisciplinary awareness,
      ii) clinical judgment and PEWS-a multi-faceted approach, iii) PEWS supports a
      professional language, iv) monitoring the patient's - a challenge, v) PEWS helps
      to visualize the need for escalating care, vi) an inflexible and challenging
      tool, and vii) supportive tools enhance the nurses' experiences of PEWS
      positively. CONCLUSIONS: Our findings suggest that attention should be given to
      nurses' perceptions of how both clinical judgment and PEWS should be seen as
      essential in providing nurses with information about the patients' conditions. If
      not, the risk of failing to recognize patients' deteriorating conditions will
      remain as this can have an impeding influence on nurses' use of PEWS. From the
      nurses' perspective, medical doctors seemed unaware of their role in using PEWS.

PMID- 29454508
TI  - The HAS-Choice study: Utilizing the HEART score, an ADP, and shared decision
      making to decrease admissions in chest pain patients.
AB  - OBJECTIVE: The HAS-Choice pathway utilizes the HEART Score, an accelerated
      diagnostic protocol (ADP), and shared decision-making using a visual aid in the
      evaluation of chest pain patients. We seek to determine if our intervention can
      improve resource utilization in a community emergency department (ED) setting
      while maintaining safe patient care. METHODS: This was a single-center
      prospective cohort study with historical that included ED patients >=21years old
      presenting with a primary complaint of chest pain in two time periods. The
      primary outcome was patient disposition. Secondary outcomes focused on 30-day ED
      bounce back and major adverse cardiac events (MACE). We used multivariate
      logistic regression to estimate the odds ratio (OR) and its 95% confidence
      interval (CI). RESULTS: In the pre-implementation period, the unadjusted
      disposition to inpatient, observation and discharge was 6.5%, 49.1% and 44.4%,
      respectively, whereas in the post period, the disposition was 4.8%, 41.5% and
      53.7%, respectively (chi-square p<0.001). The adjusted odds of a patient being
      discharged was 40% higher (OR=1.40; 95% CI, 1.30, 1.51; p<0.001) in the post
      implementation period. The adjusted odds of patient admission was 30% lower
      (OR=0.70; 95% CI, 0.60, 0.82; p<0.001) in the post-implementation period. The
      odds of 30-day ED bounce back did not statistically differ between the two
      periods. MACE rates were <1% in both periods, with a significant decrease in
      mortality in the post-implementation period. CONCLUSION: Our study suggests that
      implementation of a shared decision-making tool that integrates an ADP and the
      HEART score can safely decrease hospital admissions without an increase in MACE.

PMID- 29454509
TI  - Group C strep mediastinitis.
AB  - This case is significant to the practice of emergency medicine because it
      represents the development of an uncommon and potentially fatal mediastinal
      infection from a commonly encountered and appropriately treated community
      respiratory pathogen. Most published reports on mediastinitis are those that are
      status-post cardiothoracic surgery. In our report, we discuss a case of a
      healthy, young individual who developed this morbid entity from extension of a
      simple respiratory infection where Group C Streptococcus has been isolated as the
      causative organism, which to our knowledge has not been previously reported.
      Further, this report outlines how a community acquired pneumonia progressed to a
      life threatening illness despite proper initial treatment per local and national
      guidelines.

PMID- 29454510
TI  - Beyond thrombosis: Anti-beta2GPI domain 1 antibodies identify late pregnancy
      morbidity in anti-phospholipid syndrome.
AB  - Antibodies against beta2 glycoprotein I (anti-beta2GPI) have been identified as
      the main pathogenic autoantibody subset in anti-phospholipid syndrome (APS); the
      most relevant epitope is a cryptic and conformation-dependent structure on
      beta2GPI domain (D) 1. Anti-beta2GPI domain profiling has been investigated in
      thrombotic APS, leading to the identification of antibodies targeting D1 as the
      main subpopulation. In contrast, scarce attention has been paid to obstetric APS,
      hence this study aimed at characterizing the domain reactivity with regards to
      pregnancy morbidity (PM). To this end, 135 women with persistently positive,
      medium/high titre anti-beta2GPI IgG, without any associated systemic autoimmune
      diseases and at least one previous pregnancy were included: 27 asymptomatic
      carriers; 53 women with obstetric APS; 20 women with thrombotic APS; and 35 women
      with both thrombotic and obstetric complications. Anti-D1 and anti-D4/5
      antibodies were tested using a chemiluminescent immunoassay and a research ELISA
      assay, respectively (QUANTA Flash(r) beta2GPI Domain 1 IgG and QUANTA Lite(r)
      beta2GPI D4/5 IgG, Inova Diagnostics). Positivity for anti-D1 antibodies, but not
      anti-D4/5 antibodies, was differently distributed across the 4 subgroups of
      patients (p < 0.0001) and significantly correlated with thrombosis (chi2 = 17.28,
      p < 0.0001) and PM (chi2 = 4.28, p = 0.039). Patients with triple positivity for
      anti-phospholipid antibodies displayed higher anti-D1 titres and lower anti-D4/5
      titres compared to women with one or two positive tests (p < 0.0001 and p =
      0.005, respectively). Reactivity against D1 was identified as a predictor for PM
      (OR 2.4, 95% confidence interval [CI] 1.2-5.0, p = 0.017); in particular, anti-D1
      antibodies were predictive of late PM, conveying an odds ratio of 7.3 (95% CI 2.1
      25.5, p = 0.022). Positivity for anti-D1 antibodies was not associated with early
      pregnancy loss. Anti-D4/5 antibodies were not associated with clinical APS
      manifestations. As a whole, our data suggest that anti-D1 antibodies are
      significantly associated not only with thrombosis, but also with late PM, while
      positive anti-D4/5 antibodies are not predictive of thrombosis or PM.

PMID- 29454511
TI  - Musical deficits and cortical thickness in people with schizophrenia.
AB  - Investigation of acquired amusia caused by brain damage suggested that cortical
      lesions of the right hemisphere contributed to musical deficits. We previously
      reported reduced musical ability in schizophrenia; these deficits were correlated
      with clinical manifestations such as cognitive dysfunction and negative symptoms.
      However, the neural substrate underlying the musical disability in schizophrenia
      remains unclear. We investigated the relationship between musical deficits and
      cortical thickness in patients with schizophrenia using structural MRI. We
      recruited 24 patients (13 males; age mean=45.9years old), and 22 controls (14
      males, age mean=43.5years old). Musical ability was assessed with the Montreal
      Battery for Evaluation of Amusia (MBEA), cognitive function with the Brief
      Assessment of Cognition in Schizophrenia (BACS) and clinical features of illness
      with the Positive and Negative Syndrome Scale (PANSS). MRI Images were acquired
      and processed using FreeSurfer. Surface-based analysis showed that thinner cortex
      in left temporal and inferior frontal region was associated with lower musical
      ability in schizophrenia. In contrast, in controls thicker cortex in the left
      supramarginal region was correlated with lower musical ability. These results
      shed light on the clinical pathology underlying the associations of musical
      ability, cognitive dysfunction and negative symptoms in patients with
      schizophrenia.

PMID- 29454512
TI  - Frontal and temporal cortical volume, white matter tract integrity, and
      hemispheric asymmetry in schizotypal personality disorder.
AB  - Abnormalities in temporal and frontal cortical volume, white matter tract
      integrity, and hemispheric asymmetry have been implicated in schizophrenia
      spectrum disorders. Schizotypal personality disorder can provide insight into
      vulnerability and protective factors in these disorders without the confounds
      associated with chronic psychosis. However, multimodal imaging and asymmetry
      studies in SPD are sparse. Thirty-seven individuals with SPD and 29 healthy
      controls (HC) received clinical interviews and 3T magnetic resonance T1-weighted
      and diffusion tensor imaging scans. Mixed ANOVAs were performed on gray matter
      volumes of the lateral temporal regions involved in auditory and language
      processing and dorsolateral prefrontal cortex involved in executive functioning,
      as well as fractional anisotropy (FA) of prominent white matter tracts that
      connect frontal and temporal lobes. In the temporal lobe regions, there were no
      group differences in volume, but SPD had reduced right>left middle temporal gyrus
      volume asymmetry compared to HC and lacked the right>left asymmetry in the
      inferior temporal gyrus volume seen in HC. In the frontal regions, there were no
      differences between groups on volume or asymmetry. In the white matter tracts,
      SPD had reduced FA in the left sagittal stratum and superior longitudinal
      fasciculus, and increased right>left asymmetry in sagittal stratum FA compared to
      HC. In the SPD group, lower left superior longitudinal fasciculus FA was
      associated with greater severity of disorganization symptoms. Findings suggest
      that abnormities in structure and asymmetry of temporal regions and
      frontotemporal white matter tract integrity are implicated in SPD pathology.

PMID- 29454513
TI  - Outcomes and related factors in a cohort of infants born in Taiwan over a period
      of five years (2007-2011) with borderline viability.
AB  - BACKGROUND: Advances in perinatal and neonatal care have increased the survival
      of extremely preterm infants, but the viability limit is still debated. Here we
      assess the survival, neonatal morbidity, and neurodevelopmental outcomes at 2
      years of age of infants born at 22-26 weeks of gestation in Taiwan between 2007
      and 2011. METHODS: This is a prospective longitudinal multicenter cohort study on
      extremely preterm infants registered in the Taiwan Premature Infant Developmental
      Collaborative Study Group from 2007 to 2011, including 22 neonatal care centers.
      We extracted demographic and clinical data of infants born at 22-26 weeks, and
      obtained growth and developmental outcome data from the follow-up clinic at 24
      months of corrected age. Multivariate analyses using a logistic regression model
      identified factors significantly impacting survival. RESULTS: 647 of the 1098
      infants included in the study (58.9%) survived to discharge. Survival rates were
      8% (4/50), 25% (27/108), 46.8% (117/250), 67.0% (211/315), and 76.8% (288/375)
      for infants born at 22, 23, 24, 25, and 26 weeks, respectively. Most survivors
      (567/647, 87.6%) had major morbidities during hospitalization, and we identified
      factors that positively and negatively affected survival. 514 (79.4%) patients
      received follow-up evaluation at 2 years, and 204 (39.7%) of them had
      neurodevelopmental impairment (NDI) with an incidence of 75%, 65.2%, 49.5%,
      39.5%, and 32.8% for infants born at 22, 23, 24, 25, and 26 weeks, respectively.
      CONCLUSION: Infants born at 22 and 23 weeks have a very low likelihood of
      surviving with little or no impairment. These findings are valuable for parental
      counseling and perinatal care decisions.

PMID- 29454514
TI  - Phase 2 study evaluating intermittent and continuous linsitinib and weekly
      paclitaxel in patients with recurrent platinum resistant ovarian epithelial
      cancer.
AB  - BACKGROUND: Linsitinib, an oral, dual inhibitor of insulin-like growth factor-1
      receptor and insulin receptor, in combination with weekly paclitaxel, may improve
      clinical outcomes compared with paclitaxel alone in patients with refractory or
      platinum-resistant ovarian cancer. PATIENTS AND METHODS: This open-label phase
      1/2 clinical trial (NCT00889382) randomized patients with refractory or platinum
      resistant ovarian cancer (1:1:1) to receive either oral intermittent linsitinib
      (600mg once daily on Days 1-3 per week) combined with paclitaxel (80mg/m2 on Days
      1, 8, and 15; Arm A) or continuous linsitinib (150mg twice daily) in combination
      with paclitaxel (Arm B), or paclitaxel alone (Arm C). Primary endpoint was
      progression-free survival (PFS); secondary endpoints included overall survival
      (OS), overall response rate (ORR), disease control rate (DCR), and
      safety/tolerability. RESULTS: A total of 152 women were randomized to treatment
      (n=51 Arm A; n=51 Arm B, n=50 Arm C). In combination with paclitaxel, neither
      intermittent linsitinib (median PFS 2.8months; 95% confidence interval [CI]:2.5
      4.4) nor continuous linsitinib (median PFS 4.2months; 95% CI:2.8-5.1) improved
      PFS over weekly paclitaxel alone (median PFS 5.6months; 95% CI:3.2-6.9). No
      improvement in ORR, DCR, or OS in either linsitinib dosing schedule was observed
      compared with paclitaxel alone. Adverse event (AE) rates, including all-grade and
      grade 3/4 treatment-related AEs, and treatment-related AEs leading to
      discontinuation, were higher among patients receiving intermittent linsitinib
      compared with the other treatment arms. CONCLUSION: Addition of intermittent or
      continuous linsitinib with paclitaxel did not improve outcomes in patients with
      platinum-resistant/refractory ovarian cancer compared with paclitaxel alone.

PMID- 29454515
TI  - Quantitative profiling reveals minor changes of T cell receptor repertoire in
      response to subunit inactivated influenza vaccine.
AB  - Vaccination against influenza is widely used to protect against seasonal flu
      epidemic although its effectiveness is debated. Here we performed deep
      quantitative T cell receptor repertoire profiling in peripheral blood of a
      healthy volunteer in response to trivalent subunit influenza vaccine. We did not
      observe significant rebuilding of peripheral blood T cell receptors composition
      in response to vaccination. However, we found several clonotypes in memory T cell
      fraction that were undetectable before the vaccination and had a maximum
      concentration at day 45 after vaccine administration. These cells were found in
      lower concentration in the course of repertoire monitoring for two years period.
      Our observation suggests a potential for recruitment of only a limited number of
      new T cells after each seasonal influenza vaccination.

PMID- 29454516
TI  - Immunity against measles, mumps, rubella, varicella, diphtheria, tetanus, polio,
      hepatitis A and hepatitis B among adult asylum seekers in the Netherlands, 2016.
AB  - Asylum seekers are a vulnerable population for contracting infectious diseases.
      Outbreaks occur among children and adults. In the Netherlands, asylum seeker
      children are offered vaccination according to the National Immunization Program.
      Little is known about protection against vaccine-preventable diseases (VPD) in
      adult asylum seekers. In this 2016 study, we assessed the immunity of adult
      asylum seekers against nine VPD to identify groups that might benefit from
      additional vaccinations. We invited asylum seekers from Syria, Iran, Iraq,
      Afghanistan, Eritrea and Ethiopia to participate in a serosurvey. Participants
      provided informed consent and a blood sample, and completed a questionnaire. We
      measured prevalence of protective antibodies to measles, mumps, rubella,
      varicella, diphtheria, tetanus, polio type 1-3 and hepatitis A and B, stratified
      them by country of origin and age groups. The median age of the 622 participants
      was 28 years (interquartile range: 23-35), 81% were male and 48% originated from
      Syria. Overall, seroprotection was 88% for measles (range between countries: 83
      93%), 91% for mumps (81-95%), 94% for rubella (84-98%), 96% for varicella (92
      98%), 82% for diphtheria (65-88%), 98% for tetanus (86-100%), 91% (88-94%) for
      polio type 1, 95% (90-98%) for polio type 2, 82% (76-86%) for polio type 3, 84%
      (54-100%) for hepatitis A and 27% for hepatitis B (anti-HBs; 8-42%). Our results
      indicate insufficient protection against certain VPD in some subgroups. For all
      countries except Eritrea, measles seroprotection was below the 95% threshold
      required for elimination. Measles seroprevalence was lowest among adults younger
      than 25 years. In comparison, seroprevalence in the Dutch general population was
      96% in 2006/07. The results of this study can help prioritizing vaccination of
      susceptible subgroups of adult asylum seekers, in general and in outbreak
      situations.

PMID- 29454517
TI  - Intradermal immunization with inactivated swine influenza virus and adjuvant
      polydi(sodium carboxylatoethylphenoxy)phosphazene (PCEP) induced humoral and cell
      mediated immunity and reduced lung viral titres in pigs.
AB  - Swine influenza virus is endemic worldwide and it is responsible for significant
      economic losses to the swine industry. A vaccine that stimulates a rapid and long
      lasting protective immune response to prevent this infection is highly sought.
      Poly[di(sodium carboxylatoethylphenoxy)-phosphazene (PCEP) has demonstrated
      adjuvant activity when formulated as part of multiple vaccines in mice and pigs.
      In this study we examined the magnitude and type of immune response induced in
      pigs vaccinated via the intramuscular or intradermal routes with inactivated
      swine influenza virus (SIV) H1N1 vaccine formulated with PCEP. Intradermal
      administration of PCEP-adjuvanted inactivated SIV vaccine stimulated significant
      anti-SIV antibody titres, increased neutralizing antibodies, and significantly
      reduced lung virus load with limited reduction of gross lung lesions after
      challenge with virulent H1N1 relative to control animals. These results indicate
      that PCEP may be effective as a vaccine adjuvant against swine influenza viruses
      in pigs and should be considered a potential candidate adjuvant for future swine
      intradermal influenza vaccines.

PMID- 29454518
TI  - Use of a new global indicator for vaccine safety surveillance and trends in
      adverse events following immunization reporting 2000-2015.
AB  - Reporting of adverse events following immunization (AEFI) is a key component for
      functional vaccine safety monitoring system. The aim of our study is to document
      trends in the AEFI reporting ratio globally and across the six World Health
      Organization (WHO) regions. We describe the number of AEFI reports communicated
      each year through the World Health Organization/United Nations Children's Fund
      Joint Reporting Form on Immunization from 2000 to 2015. The AEFI reporting ratios
      (annual AEFI reports per 100,000 surviving infants) were calculated to identify
      WHO countries (n = 191 in 2000 and n = 194 by 2015) that met a minimal reporting
      ratio of 10, a target set by the Global Vaccine Action Plan for vaccine safety
      monitoring as a proxy measure for a functional AEFI reporting system. The number
      of countries reporting any AEFI fluctuated over time but with progress from 32
      (17%) in 2000 to 124 (64%) in 2015. In 2015, the global average AEFI reporting
      ratio was 549 AEFI reports per 100,000 surviving infants. The number of countries
      with AEFI reporting ratios greater than 10 increased from 8 (4%) in 2000 to 81
      (42%) in 2015. In 2015, 60% of countries in the WHO Region of the Americas
      reported at least 10 AEFI per 100,000 surviving infants, followed by 55% in
      European Region, 43% in Eastern Mediterranean Region, 33% in Western Pacific
      Region, 27% in South-East Asia Region and 21% in African Region. Overall, AEFI
      reporting has increased over the past sixteen years worldwide, but requires
      strengthening in a majority of low- and middle- income countries. The AEFI
      reporting ratio is useful for benchmarking and following trends over time; but
      does not provide information on the quality of the reporting system and does not
      guarantee capacity to detect and manage a vaccine safety problem at a national
      level. Additional efforts are required to ensure and improve data quality, AEFI
      reporting and surveillance of immunization safety in every country.

PMID- 29454520
TI  - Ad hominem attacks on vaccine safety researchers.

PMID- 29454519
TI  - High resolution age-structured mapping of childhood vaccination coverage in low
      and middle income countries.
AB  - BACKGROUND: The expansion of childhood vaccination programs in low and middle
      income countries has been a substantial public health success story. Indicators
      of the performance of intervention programmes such as coverage levels and numbers
      covered are typically measured through national statistics or at the scale of
      large regions due to survey design, administrative convenience or operational
      limitations. These mask heterogeneities and 'coldspots' of low coverage that may
      allow diseases to persist, even if overall coverage is high. Hence, to decrease
      inequities and accelerate progress towards disease elimination goals, fine-scale
      variation in coverage should be better characterized. METHODS: Using measles as
      an example, cluster-level Demographic and Health Surveys (DHS) data were used to
      map vaccination coverage at 1 km spatial resolution in Cambodia, Mozambique and
      Nigeria for varying age-group categories of children under five years, using
      Bayesian geostatistical techniques built on a suite of publicly available
      geospatial covariates and implemented via Markov Chain Monte Carlo (MCMC)
      methods. RESULTS: Measles vaccination coverage was found to be strongly predicted
      by just 4-5 covariates in geostatistical models, with remoteness consistently
      selected as a key variable. The output 1 * 1 km maps revealed significant
      heterogeneities within the three countries that were not captured using province
      level summaries. Integration with population data showed that at the time of the
      surveys, few districts attained the 80% coverage, that is one component of the
      WHO Global Vaccine Action Plan 2020 targets. CONCLUSION: The elimination of
      vaccine-preventable diseases requires a strong evidence base to guide strategies
      and inform efficient use of limited resources. The approaches outlined here
      provide a route to moving beyond large area summaries of vaccination coverage
      that mask epidemiologically-important heterogeneities to detailed maps that
      capture subnational vulnerabilities. The output datasets are built on open data
      and methods, and in flexible format that can be aggregated to more operationally
      relevant administrative unit levels.

PMID- 29454521
TI  - Hepatitis B vaccination and the putative risk of central demyelinating diseases -
      A systematic review and meta-analysis.
AB  - BACKGROUND: The anti-hepatitis B immunization campaigns launched in the early
      1990s were a major public health breakthrough and targeted various populations
      (at-risk adults, newborns, adolescents). However, debate is still active about a
      possible link between this vaccine and central demyelination. This study provides
      a pooled estimate of this risk based on a comprehensive review and meta-analysis
      of all available epidemiologic studies. METHODS: A systematic review was
      conducted in Medline, Embase, ISI Web of Science and the Cochrane Library from
      database inception to 10 May 2017. Grey literature was searched and snowballing
      was also undertaken. Only observational studies including a control group were
      retained. Primary outcome was multiple sclerosis diagnosed by recognized
      criteria. Study selection was performed by two independent reviewers with
      disagreements solved through discussion. This meta-analysis based on crude,
      adjusted estimates, or risks limited to the 3 months following immunization was
      performed using a generic inverse variance random-effect model. Heterogeneity was
      investigated; sensitivity and subgroup analyses were performed when necessary.
      This study followed the PRISMA statement and the MOOSE reporting guideline (Study
      protocol registered in PROSPERO: CRD42015020808). FINDINGS: Of the 2804
      references reviewed, 13 studies with a control group were analysed. None of the
      pooled risk estimates for either multiple sclerosis or central demyelination
      following HB immunization reached statistical significance. When considering
      adjusted risk ratios, the following non-significant figures were obtained: 1.19
      (95%CI: 0.93 - 1.52) and 1.25 (95%CI: 0.97 - 1.62), for multiple sclerosis and
      central demyelination, respectively. CONCLUSIONS: No evidence of an association
      between hepatitis B vaccination and central demyelination was found.

PMID- 29454522
TI  - Genetic and subunit vaccines based on the stem domain of the equine influenza
      hemagglutinin provide homosubtypic protection against heterologous strains.
AB  - H3N8 influenza virus strains have been associated with infectious disease in
      equine populations throughout the world. Although current vaccines for equine
      influenza stimulate a protective humoral immune response against the surface
      glycoproteins, disease in vaccinated horses has been frequently reported,
      probably due to poor induction of cross-reactive antibodies against non-matching
      strains. This work describes the performance of a recombinant protein vaccine
      expressed in prokaryotic cells (DeltaHAp) and of a genetic vaccine (DeltaHAe),
      both based on the conserved stem region of influenza hemagglutinin (HA) derived
      from A/equine/Argentina/1/93 (H3N8) virus. Sera from mice inoculated with these
      immunogens in different combinations and regimes presented reactivity in vitro
      against highly divergent influenza virus strains belonging to phylogenetic groups
      1 and 2 (H1 and H3 subtypes, respectively), and conferred robust protection
      against a lethal challenge with both the homologous equine strain (100%) and the
      homosubtypic human strain A/Victoria/3/75 (H3N2) (70-100%). Animals vaccinated
      with the same antigens but challenged with the human strain A/PR/8/34 (H1N1),
      belonging to the phylogenetic group 1, were not protected (0-33%). Combination of
      protein and DNA immunogens showed higher reactivity to non-homologous strains
      than protein alone, although all vaccines were permissive for lung infection.

PMID- 29454523
TI  - A New Bifurcation Inside the Old One.

PMID- 29454524
TI  - An Unusual Cause of Haematemesis.

PMID- 29454525
TI  - Radial umbilical dermatofasciolysis to invert the skin following umbilical
      herniorrhaphy.
AB  - BACKGROUND: Umbilical hernia is a common congenital anomaly, and can result in
      the appearance of a protuberant umbilicus. In select cases, inversion of the
      umbilical skin can be impaired by the presence of thickened dermis or fascial
      remnants of the umbilical stalk. DESCRIPTION OF OPERATIVE TECHNIQUE: After
      umbilical herniorrhaphy, the skin is everted over the left index finger and
      radial partial thickness incisions in the fascia and dermis of the undersurface
      of the umbilicus. The umbilical skin is then inverted and secured to the fascia.
      CONCLUSION: This operative technique can allow complete inversion of the
      umbilical skin creating an aesthetically appealing umbilical hernia repair.

PMID- 29454526
TI  - Predicting sexual problems in young adults with an anorectal malformation or
      Hirschsprung disease.
AB  - AIM: The aim of this study was to examine the prevalence of sexual dysfunction
      and distress and to assess whether sexual functioning could be predicted by
      psychosocial factors in childhood and adolescence in patients with an anorectal
      malformation or Hirschsprung disease. MATERIAL AND METHODS: In 1998 patients
      completed a psychosocial questionnaire: The Self-Perception profile. To assess
      the prevalence of sexual distress and sexual functioning in adulthood (2015) the
      Female Sexual Function Index (FSFI), The Female Sexual Distress Scale (FSDS) and
      the International Index of Erectile Functioning (IIEF) were used. RESULTS: In
      total 74 patients returned the questionnaires (26.2%). 36.8% of women reported
      sexual dysfunction and 45% experienced sexual distress. In our male sample 8.8%
      reported mild to moderate erectile dysfunction. In females perceived self
      competence in adolescence was associated with sexual distress (p<.01). In male
      adolescents associations were found between perceived self-competence in romantic
      relations (p<.01) and in close friendships (p<.05) and sexual desire in
      adulthood. CONCLUSION: Pediatric surgeons should be more aware of sexual problems
      patients may face at older age as a result of their congenital disease and
      treatment. More standardized care and follow-up are needed. Prognosis study-Level
      II.

PMID- 29454527
TI  - WITHDRAWN: Cardiac Calendar 2016-2020.

PMID- 29454528
TI  - Continuous Infusion versus Intermittent Bolus Injection of Furosemide in
      Critically Ill Patients: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: Fluid overload is a common phenomenon seen in intensive care units
      (ICUs). However, there is no general consensus on whether continuous or bolus
      furosemide is safer or more effective in these hemodynamically unstable ICU
      patients. The aim of this meta-analysis was to examine the clinical outcomes of
      continuous versus bolus furosemide in a critically ill population in ICUs. DATA
      SOURCES: MEDLINE, EMBASE, PubMed, and the Cochrane Database of Systematic reviews
      were searched from their inception until June 2017. REVIEW METHODS: All
      randomized controlled trials, observational studies, and case-control studies
      were included. Case reports, case series, nonsystematic reviews, and studies that
      involved children were excluded. RESULTS: Nine studies (n = 464) were eligible in
      the data synthesis. Both continuous and bolus furosemide resulted in no
      difference in all-cause mortality (7 studies; n = 396; I2 = 0%; fixed-effect
      model [FEM]: odds ratio [OR] 1.15 [95% confidence interval (CI) 0.67-1.96]; p =
      0.64). Continuous furosemide was associated with significant greater total urine
      output (n = 132; I2 = 70%; random-effect model: OR 811.19 [95% CI 99.84
      1,522.53]; p = 0.03), but longer length of hospital stay (n = 290; I2 = 40%; FEM:
      OR 2.84 [95% CI 1.74-3.94]; p < 0.01) in comparison to the bolus group. No
      statistical significance was found in the changes of creatinine and estimated
      glomerular filtration rate between both groups. CONCLUSIONS: In this meta
      analysis, continuous furosemide was associated with greater diuretic effect in
      total urine output as compared with bolus. Neither had any differences in
      mortality and changes of renal function tests. However, a large adequately
      powered randomized clinical trial is required to fill this knowledge gap.

PMID- 29454529
TI  - Retention prediction in reversed phase high performance liquid chromatography
      using quantitative structure-retention relationships applied to the Hydrophobic
      Subtraction Model.
AB  - Quantitative Structure-Retention Relationships (QSRR) methodology combined with
      the Hydrophobic Subtraction Model (HSM) have been utilized to accurately predict
      retention times for a selection of analytes on several different reversed phase
      liquid chromatography (RPLC) columns. This approach is designed to facilitate
      early prediction of co-elution of analytes, for example in pharmaceutical drug
      discovery applications where it is advantageous to predict whether impurities
      might be co-eluted with the active drug component. The QSRR model utilized
      VolSurf+ descriptors and a Partial Least Squares regression combined with a
      Genetic Algorithm (GA-PLS) to predict the solute coefficients in the HSM. It was
      found that only the hydrophobicity (eta'H) term in the HSM was required to give
      the accuracy necessary to predict potential co-elution of analytes. Global QSRR
      models derived from all 148 compounds in the dataset were compared to QSRR models
      derived using a range of local modelling techniques based on clustering of
      compounds in the dataset by the structural similarity of compounds (as
      represented by the Tanimoto similarity index), physico-chemical similarity of
      compounds (represented by log D), the neutral, acidic, or basic nature of the
      compound, and the second dominant interaction between analyte and stationary
      phase after hydrophobicity. The global model showed reasonable prediction
      accuracy for retention time with errors of 30 s and less for up to 50% of modeled
      compounds. The local models for Tanimoto, nature of the compound and second
      dominant interaction approaches all exhibited prediction errors less than 30 s in
      retention time for nearly 70% of compounds for which models could be derived.
      Predicted retention times of five representative compounds on nine reversed-phase
      columns were compared with known experimental retention data for these columns
      and this comparison showed that the accuracy of the proposed modelling approach
      is sufficient to reliably predict the retention times of analytes based only on
      their chemical structures.

PMID- 29454530
TI  - System dynamics model of taxi management in metropolises: Economic and
      environmental implications for Beijing.
AB  - Taxis are an important component of urban passenger transport. Research on the
      daily dispatching of taxis and the utility of governmental management is
      important for the improvement of passenger travel, taxi driver income and
      environmental impacts. However, urban taxi management is a complex and dynamic
      system that is affected by many factors, and positive/negative feedback
      relationships and nonlinear interactions exist between each subsystem and
      variable. Therefore, conventional research methods can hardly depict its
      characteristics comprehensively. To bridge this gap, this paper develops a system
      dynamics model of urban taxi management, in which the empty-loaded rate and total
      demand are selected as key factors affecting taxi dispatching, and the impacts of
      taxi fares on driver income and travel demand are taken into account. After the
      validation of the model, taxi operations data derived from a prior analysis of
      origin-destination data of Beijing taxis are used as input for the model to
      simulate the taxi market in Beijing. Finally, economic and environmental
      implications are provided for the government to optimise policies on taxi
      management.

PMID- 29454531
TI  - Orbital atherectomy for the treatment of small (2.5mm) severely calcified
      coronary lesions: ORBIT II sub-analysis.
AB  - OBJECTIVES: We assessed the safety and efficacy of orbital atherectomy to modify
      severely calcified coronary plaque prior to stent implantation in patients with
      small vessel (2.5mm) disease. BACKGROUND: Severe coronary artery calcification
      increases the risk of adverse clinical events during percutaneous coronary
      intervention (PCI). Patients who undergo PCI of small vessels have worse clinical
      outcomes including higher rates of perforation and dissection. The outcomes of
      orbital atherectomy of small diameter vessels (2.5mm) are unknown. METHODS: ORBIT
      II was a single-arm, multicenter trial which prospectively enrolled patients with
      severely calcified coronary lesions treated with orbital atherectomy prior to
      stenting in 49U.S. sites. The primary endpoint was the 3year rate of major
      adverse cardiac events, which was the composite of cardiac death, myocardial
      infarction, and target vessel revascularization. RESULTS: Of the 443 patients, 55
      (12.4%) had reference vessel diameters (RVD) of 2.5mm and 388 (87.6%) had RVD
      >2.5. The rates of severe angiographic complications were similar in both groups.
      The primary endpoint was similar in both groups (30.6% vs. 22.5%, p=0.22), as
      were the rates of cardiac death (9.8% vs. 6.3%, p=0.33) and myocardial infarction
      (12.8% vs. 10.9%, p=0.67). Target vessel revascularization was numerically higher
      in the small vessel group (16.8% vs. 9.3%, p=0.13). CONCLUSIONS: Patients with
      small coronary vessel disease had comparable clinical outcomes compared to the
      larger diameter group following orbital atherectomy. Subsequent studies are
      required to establish the optimal revascularization approach for such patients
      with small coronary vessel disease burdened by heavily calcified lesions.

PMID- 29454532
TI  - Outcomes after magnetic resonance imaging in patients with pacemakers and
      defibrillators and abandoned leads.

PMID- 29454533
TI  - Statistical comments on "Does player time-in-game affect tackle technique in
      elite level rugby union?"

PMID- 29454534
TI  - Sarcomatoid Carcinoma of the Lung: The Mayo Clinic Experience in 127 Patients.
AB  - BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is an unusual form of non-small
      cell lung cancer (NSCLC). Because of its rarity and heterogeneity, the treatment
      and prognosis of PSC have not been clearly described. METHODS AND MATERIALS: We
      retrospectively evaluated all patients with a diagnosis of PSC from 1997 to 2015
      at the Mayo Clinic (Rochester, MN). The clinical characteristics, treatment
      details, and outcomes were collected. The survival rates of the PSC patients were
      compared with those for other subtypes of NSCLC. We used propensity score
      matching to minimize the bias resulting from to imbalanced comparison groups.
      RESULTS: The study included 127 PSC patients. The median age at diagnosis was 68
      years (range, 32-89 years), most of whom were men (61%) and smokers (82%). The
      clinical stage was I, II, III, and IV in 15.9%, 20.6%, 22.2%, and 41.3%,
      respectively. The median survival time was 9.9 months (95% confidence interval
      [CI], 7.6-12.6 months). The 1-, 2-, and 5-year survival rates were 42%, 23%, and
      15%, respectively. Most patients received multimodality treatment. Of the 3
      patients who received neoadjuvant chemotherapy, a partial response was
      demonstrated in 2. Twenty-five patients who underwent palliative chemotherapy
      were evaluated for tumor response: 52% experienced progression, 40% stable
      disease, 8.0% a partial response, and 0% a complete response. Multivariate
      analysis showed T stage, M stage, and treatment with surgery plus neoadjuvant
      chemotherapy or surgery plus adjuvant therapy were independent prognostic factors
      (P < .05). In matched analysis, multivariate models revealed worse overall
      survival for PSC compared with adenocarcinoma (hazard ratio, 2.38; 95% CI, 1.61
      2.53) and squamous cell carcinoma (hazard ratio, 2.20; 95% CI, 1.44-2.34).
      CONCLUSION: We found the outcome of PSC to be significantly worse than that of
      adenocarcinoma and squamous cell carcinoma. Neoadjuvant or adjuvant chemotherapy,
      in addition to surgical resection, should be considered.

PMID- 29454535
TI  - Insurance-mandated preoperative diet and outcomes after bariatric surgery.
AB  - BACKGROUND: Despite a lack of demonstrated patient benefit, many insurance
      providers mandate a physician-supervised diet before financial coverage for
      bariatric surgery. OBJECTIVES: To compare weight loss between patients with
      versus without insurance mandating a preoperative diet. SETTING: University
      hospital, United States. METHODS: Retrospective study of all patients who
      underwent laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy over a 5
      year period, stratified based on whether an insurance-mandated physician
      supervised diet was required. Weight loss outcomes at 6, 12, and 24 months
      postoperation were compared. Linear mixed-models and backward-stepwise selection
      were used. P<0.05 was considered significant. RESULTS: Of 284 patients, 225 (79%)
      were required and 59 (21%) were not required to complete a preoperative diet by
      their insurance provider. Patients without the requirement had a shorter time to
      operation from initial consultation (P = .04), were older (P<.01), and were more
      likely to have government-sponsored insurance (P<.01). There was no difference in
      preoperative weight or body mass index or co-morbidities. In unadjusted models,
      percent excess weight loss was superior in the group without an insurance
      mandated diet at 12 (P = .050) and 24 (P = .045) months. In adjusted analyses,
      this group also had greater percent excess weight loss at 6 (P<.001), 12
      (P<.001), and 24 (P<.001) months; percent total weight loss at 24 months (P =
      .004); and change in body mass index at 6 (P = .032) and 24 (P = .007) months.
      There was no difference in length of stay or complication rates. CONCLUSIONS:
      Insurance-mandated preoperative diets delay treatment and may lead to inferior
      weight loss.

PMID- 29454536
TI  - The role of the OVOL1-OVOL2 axis in normal and diseased human skin.
AB  - OVOLs (OVO-like proteins) are ubiquitously conserved genes encoding a C2H2 zinc
      finger transcription factor in mammals. Functional studies on OVOL1 and OVOL2
      using knockout mice have suggested that these genes play a pivotal role in the
      development of epithelial tissues arising from germ cells; however, the role of
      the OVOL1-OVOL2 axis in normal and diseased tissues remains unclear. This review
      highlights recent advances in understanding how the OVOL1-OVOL2 axis modulates
      cell differentiation and proliferation in human keratinocytes, hair follicles,
      and benign or malignant skin tumors including squamous cell carcinoma and
      malignant melanoma. Furthermore, OVOL1 has been shown to be involved in the
      expression of skin barrier proteins including filaggrin (FLG), and its mutation
      or dysfunction leads to the development of atopic dermatitis (AD). OVOL1 has also
      been identified as a susceptibility gene for AD by genome-wide association
      studies, in addition to FLG. Therefore, we discuss the relationship between OVOL1
      and FLG in the development of AD.

PMID- 29454537
TI  - An infant with generalized pustular psoriasis and geographic tongue had a
      heterozygous IL36RN mutation and IgG2 deficiency.

PMID- 29454538
TI  - Cobalamin deficiency presenting with thrombotic microangiopathy (TMA) features: A
      systematic review.
AB  - INTRODUCTION: Cobalamin deficiency may result in hematologic characteristics
      similar to thrombotic microangiopathy (TMA). To facilitate diagnosis, we reviewed
      reported cases of acquired cobalamin deficiency presenting with TMA features
      (c.def-TMA). METHODS: A literature search identified reports of c.def-TMA.
      Deficiency was defined as B12 levels of <118 pmol/L. Corrected reticulocyte
      counts and reticulocyte production indexes were calculated. Clinical features
      were presented as proportion abnormal and results summarized as medians and
      interquartile ranges (IQR). RESULTS: Patient level data was extracted from 41
      identified cases. Median age (years) was 43 (30-55) with 21/41 (51%) being
      female. Cobalamin deficiency was noted in 35/40 (87.5%) but fold increases in MMA
      and HC were 30 and 6, respectively. The etiology was pernicious anemia in 28/41
      (68%) cases. Anemia was both universal and severe, with hemoglobin levels of 55
      g/L (4.7-6.6). Hypersegmented neutrophils were noted in 23/37 (62%), schistocytes
      in 29/38 (76%) and median LDH levels 3981 U/L (2004-5467). The RPI was <3.0% in
      all patients. Thrombocytopenia occurred in 33/41 (80.5%) with a median platelet
      count of 91 * 109/L (42-112). Plasma infusion or exchange was initiated in 14/41
      (34%) with associated complications in 2 cases. CONCLUSION: Reticulocytopenia
      (RPI of <3.0%) was a universal finding that aids in differentiating c.def-TMA
      from other causes of hemolysis. C.def-TMA was associated with severe anemia,
      generally mild-moderate thrombocytopenia, and significant elevations in LDH.

PMID- 29454539
TI  - Quantification of the risk of urinary calcium stone formation in the urine
      collected at 2 times of the day in a group of children studied to rule out
      prelithiasis.
AB  - BACKGROUND: Various genetic and environmental factors are involved in
      urolithiasis. The 2 most common metabolic abnormalities are the increase in
      urinary calcium and low urinary citrate excretion. The ratio calculated between
      the concentrations of both substances is a good risk marker for the formation of
      calcium stones. OBJECTIVES: To determine whether the risk of urinary calcium
      stone formation changes throughout the day in the same patient. METHODS: We
      studied 56 children (23V, 33M) to check if they had prelithiasis. Calcium,
      citrate, and creatinine concentrations were determined in two urine samples
      collected one before dinner and the other in the morning. It was collected if
      they had ultrasound stones and if there was a history of urolithiasis in first
      and/or second degree relatives. RESULTS: In 25 patients (44.6%), renal ultrasound
      was positive for lithiasis (stones [n=9] and microlithiasis [n=16]). Forty of the
      56 families (71.4%) had a history of urolithiasis. The percentage of abnormal
      urinary calcium (28.6%) concentrations and an abnormal calcium/citrate ratio
      (69.6%) was higher in the first urine of the day. The calcium/citrate ratio was
      the only studied parameter that was related to a family history of urolithiasis.
      There were no differences in urinary parameters between patients with and without
      ultrasound-confirmed kidney stones. CONCLUSIONS: Urinary concentrations of
      calcium and the calcium/citrate ratio vary throughout the day. Urine produced at
      night has a higher risk of urinary calcium stone formation.

PMID- 29454540
TI  - Asymmetric cellulose triacetate is a safe and effective alternative for online
      haemodiafiltration.
AB  - BACKGROUND: In post-dilution haemodiafiltration only synthetic membranes have
      been used to date. Asymmetric cellulose triacetate (ATATM) is now available,
      whose characteristics are suitable for this technique. OBJECTIVES: To describe
      the in vivo performance and behaviour of this membrane, to identify its
      depurative effectiveness, use in clinical practice and its biocompatibility, both
      acute and after one month of treatment. METHODS: Observational prospective study
      of 23 patients who were dialysed for 4 weeks using an ATATM membrane and who
      maintained their prior regimen. RESULTS: A total of 287 sessions were performed
      and 264 complete sessions were collected. With an effective time of 243.7 (17.6)
      min and a mean blood flow of 371.7 (23) ml/min, an average Kt of 56.3 (5.3) l was
      observed, as well as a convection volume of 27.1 (4.2) l, a filtration fraction
      of 29.9 (3.7) %, a urea reduction ratio (RR) of 81 (5.2) %, a creatinine RR of
      74.7 (4.6) %, a beta2-microglobulin RR of 76.5 (4.8) % and a retinol binding
      protein RR of 18.6 (7.6) %. There were no technical problems or alarms. Changing
      the heparin dosage was not necessary. No increases in C3a or C5a concentrations
      or leukopenia were observed in the first 30min of the session. Neither the
      monocyte subpopulations nor IL-beta1 or IL-6 were significantly altered after one
      month of treatment. CONCLUSIONS: The new ATATM membrane achieves adequate Kt and
      convection volume, without technical problems and with good biocompatibility and
      inflammatory profiles. It is therefore a valid option for post-dilution
      haemodiafiltration, particularly in patients allergic to synthetic membranes.

PMID- 29454541
TI  - Participants, Physicians or Programmes: Participants' educational level and
      initiative in cancer screening.
AB  - This study is an in-depth examination of at whose initiative (participant,
      physician or screening programme) individuals participate in cervical, breast and
      colorectal cancer screening across the EU-28. Special attention is paid to (1)
      the association with educational attainment and (2) the country's cancer
      screening strategy (organised, pilot/regional or opportunistic) for each type of
      cancer screened. Data were obtained from Eurobarometer 66.2 'Health in the
      European Union' (2006). Final samples consisted of 10,186; 5443 and 9851
      individuals for cervical, breast, and colorectal cancer, respectively.
      Multinomial logistic regressions were performed. Surprisingly, even in countries
      with organised screening programmes, participation in screenings for cervical,
      breast and colorectal cancer was most likely to be initiated by the general
      practitioner (GP) or the participant. In general, GPs were found to play a
      crucial role in making referrals to screenings, regardless of the country's
      screening strategy. The results also revealed differences between educational
      groups with regard to their incentive to participate in cervical and breast
      cancer screening and, to a lesser extent, in colorectal cancer screening. People
      with high education are more likely to participate in cancer screening at their
      own initiative, while people with less education are more likely to participate
      at the initiative of a physician or a screening programme. Albeit, the results
      varied according to type of cancer screening and national screening strategy.

PMID- 29454542
TI  - Classifying running speed conditions using a single wearable sensor: Optimal
      segmentation and feature extraction methods.
AB  - Accelerometers have been used to classify running patterns, but classification
      accuracy and computational load depends on signal segmentation and feature
      extraction. Stride-based segmentation relies on identifying gait events, a step
      avoided by using window-based segmentation. For each segment, discrete points can
      be extracted from the accelerometer signal, or advanced features can be computed.
      Therefore, the purpose of this study was to examine how different segmentation
      and feature extraction methods influence the accuracy and computational load of
      classifying running conditions. Forty-four runners ran at their preferred speed
      and 25% faster than preferred while an accelerometer at the lower back recorded
      3D accelerations. Computational load was determined as the accelerometer signal
      was segmented into single and five strides, and corresponding small and large
      windows, with discrete points extracted from the single stride segments and
      advanced features computed from all four segment types. Each feature set was used
      to classify speed conditions and classification accuracy was recorded.
      Computational load and classification accuracy were compared across all feature
      sets using a repeated-measures MANOVA, with follow-up t-tests to compare feature
      type (discrete vs. advanced), segmentation method (stride- vs. window-based), and
      segment size (small vs. large), using a Bonferroni-adjusted alpha = 0.003. The
      five-stride (97.49 (+/-4.57)%) and large-window advanced (97.23 (+/-5.51)%)
      feature sets produced the greatest classification accuracy, but the large-window
      advanced feature set had a lower computational load (0.0041 (+/-0.0002)s) than
      the stride-based feature sets. Therefore, using a few advanced features and large
      overlapping window sizes yields the best performance of both classification
      accuracy and computational load.

PMID- 29454543
TI  - Characterization of the passive and active material parameters of the
      pubovisceralis muscle using an inverse numerical method.
AB  - The mechanical characteristics of the female pelvic floor are relevant to
      understand pelvic floor dysfunctions (PFD), and how they are related with changes
      in their biomechanical behavior. Urinary incontinence (UI) and pelvic organ
      prolapse (POP) are the most common pathologies, which can be associated with
      changes in the mechanical properties of the supportive structures in the female
      pelvic cavity. PFD have been studied through different methods, from experimental
      tensile tests using tissues from fresh female cadavers or tissues collected at
      the time of a transvaginal hysterectomy procedure, or by applying imaging
      techniques. In this work, an inverse finite element analysis (FEA) was applied to
      understand the passive and active behavior of the pubovisceralis muscle (PVM)
      during Valsalva maneuver and muscle active contraction, respectively. Individual
      numerical models of women without pathology, with stress UI (SUI) and POP were
      built based on magnetic resonance images, including the PVM and surrounding
      structures. The passive and active material parameters obtained for a
      transversely isotropic hyperelastic constitutive model were estimated for the
      three groups. The values for the material constants were significantly higher for
      the women with POP when compared with the other two groups. The PVM of women with
      POP showed the highest stiffness. Additionally, the influence of these parameters
      was analyzed by evaluating their stress-strain, and force-displacements
      responses. The force produced by the PVM in women with POP was 47% and 82% higher
      when compared to women without pathology and with SUI, respectively. The inverse
      FEA allowed estimating the material parameters of the PVM using input information
      acquired non-invasively.

PMID- 29454544
TI  - Mapping the spatiotemporal evolution of solute transport in articular cartilage
      explants reveals how cartilage recovers fluid within the contact area during
      sliding.
AB  - The interstitial fluid within articular cartilage shields the matrix from
      mechanical stresses, reduces friction and wear, enables biochemical processes,
      and transports solutes into and out of the avascular extracellular matrix. The
      balanced competition between fluid exudation and recovery under load is thus
      critical to the mechanical and biological functions of the tissue. We recently
      discovered that sliding alone can induce rapid solute transport into buried
      cartilage contact areas via a phenomenon termed tribological rehydration. In this
      study, we use in situ confocal microscopy measurements to track the
      spatiotemporal propagation of a small neutral solute into the buried contact area
      to clarify the fluid mechanics underlying the tribological rehydration
      phenomenon. Sliding experiments were interrupted by periodic static loading to
      enable scanning of the entire contact area. Spatiotemporal patterns of solute
      transport combined with tribological data suggested pressure driven flow through
      the extracellular matrix from the contact periphery rather than into the surface
      via a fluid film. Interestingly, these testing interruptions also revealed
      dynamic, repeatable and history-independent fluid loss and recovery processes
      consistent with those observed in vivo. Unlike the migrating contact area, which
      preserves hydration by moving faster than interstitial fluid can flow, our
      results demonstrate that the stationary contact area can maintain and actively
      recover hydration through a dynamic competition between load-induced exudation
      and sliding-induced recovery. The results demonstrate that sliding contributes to
      the recovery of fluid and solutes by cartilage within the contact area while
      clarifying the means by which it occurs.

PMID- 29454545
TI  - Characterization of Urinary Stone Composition by Use of Whole-body, Photon
      counting Detector CT.
AB  - RATIONAL AND OBJECTIVES: This study aims to investigate the performance of a
      whole-body, photon-counting detector (PCD) computed tomography (CT) system in
      differentiating urinary stone composition. MATERIALS AND METHODS: Eighty-seven
      human urinary stones with pure mineral composition were placed in four
      anthropomorphic water phantoms (35-50 cm lateral dimension) and scanned on a PCD
      CT system at 100, 120, and 140 kV. For each phantom size, tube current was
      selected to match CTDIvol (volume CT dose index) to our clinical practice. Energy
      thresholds at [25, 65], [25, 70], and [25, 75] keV for 100, 120, and 140 kV,
      respectively, were used to generate dual-energy images. Each stone was
      automatically segmented using in-house software; CT number ratios were calculated
      and used to differentiate stone types in a receiver operating characteristic
      (ROC) analysis. A comparison with second- and third-generation dual-source, dual
      energy CT scanners with conventional energy integrating detectors (EIDs) was
      performed under matching conditions. RESULTS: For all investigated settings and
      smaller phantoms, perfect separation between uric acid and non-uric acid stones
      was achieved (area under the ROC curve [AUC] = 1). For smaller phantoms,
      performance in differentiation of calcium oxalate and apatite stones was also
      similar between the three scanners: for the 35-cm phantom size, AUC values of
      0.76, 0.79, and 0.80 were recorded for the second- and third-generation EID-CT
      and for the PCD-CT, respectively. For larger phantoms, PCD-CT and the third
      generation EID-CT outperformed the second-generation EID-CT for both
      differentiation tasks: for a 50-cm phantom size and a uric acid/non-uric acid
      differentiating task, AUC values of 0.63, 0.95, and 0.99 were recorded for the
      second- and third-generation EID-CT and for the PCD-CT, respectively. CONCLUSION:
      PCD-CT provides comparable performance to state-of-the-art EID-CT in
      differentiating urinary stone composition.

PMID- 29454546
TI  - Corrigendum to "Manual calf massage and passive ankle motion reduce the incidence
      of deep vein thromboembolism after total hip arthroplasty" [J Orthop Sci 22
      (2017) 726-730].

PMID- 29454547
TI  - Long-term results of autologous bone marrow mesenchymal stem cell transplantation
      for cartilage defects in the patella: Two case reports with more than 18 years of
      follow-up.

PMID- 29454548
TI  - Correlation between molecular tumor volume evaluated with 68Ga-PSMA PET/CT and
      prostatic specific antigen levels.
AB  - OBJECTIVE: To investigate the association between prostatic-specific antigen
      (PSA) levels and molecular tumor volume (MTV) measured in the 68Ga-PSMA PET/CT,
      both done in a short period of time, in prostate cancer patients with biochemical
      failure. METHODS: Eighty-four patients who underwent 68Ga-PSMA PET/CT and
      measurement of PSA levels in the same week (trigger-PSA) were studied in this
      retrospective analysis. MTV was calculated from the sum of the metastatic
      lesions. To determine the association between trigger-PSA level and PET/CT
      findings, Spearman rank correlation was used. RESULTS: The median MTV of
      metastatic bone disease (mBD) was significantly higher than in metastatic lymph
      nodes (mLN) (139.5 versus 17.7; P<.05). Disease was limited to the prostate in 8
      patients (9.5%), mLN in 21 patients (25%), mBD in 32 patients (38.1%) and the 3
      sites (prostate, mLN, and mBD) in 17 patients (20.2%). In 6 patients (6.14%),
      68Ga-PSMA-PET/CT was not capable of detecting disease. The median trigger-PSA
      levels of patients with disease limited to the prostate (2.8ng/mL), mLN
      (6.8ng/mL), and for mBD (16.8ng/mL) was statically significant (P<.05). Positive
      patients had a mean trigger-PSA of 4.3ng/mL vs 1.5ng/mL in negative patients
      (P<.05). We established 3 threshold-points for trigger-PSA level detection
      rate:<=1ng/mL (47.3%), 1-4ng/mL (68.4%) and>=4ng/mL (96.7%). When trigger-PSA
      exceeded 4ng/mL, the MTV was higher (P<.001). CONCLUSION: The correlation of MTV
      with trigger-PSA is demonstrated, which may have an impact on management.
      However, trigger-PSA levels were not capable of distinguishing between localized
      or distant disease. An accurate detection of disease can lead to a better
      therapeutic strategy.

PMID- 29454549
TI  - Technology Advances to Improve Response to Cardiac Resynchronization Therapy:
      What Clinicians Should Know.
AB  - Cardiac resynchronization therapy (CRT) is a well-established treatment for
      symptomatic heart failure patients with reduced left ventricular ejection
      fraction, prolonged QRS duration, and abnormal QRS morphology. The ultimate goals
      of modern CRT are to improve the proportion of patients responding to CRT and to
      maximize the response to CRT in patients who do respond. While the rate of CRT
      nonresponders has moderately but progressively decreased over the last 20 years,
      mostly in patients with left bundle branch block, in patients without left bundle
      branch block the response rate is almost unchanged. A number of technological
      advances have already contributed to achieve some of the objectives of modern
      CRT. They include novel lead design (the left ventricular quadripolar lead, and
      multipoint pacing), or the possibility to go beyond conventional delivery of CRT
      (left ventricular endocardial pacing, His bundle pacing). Furthermore, to improve
      CRT response, a triad of actions is paramount: reducing the burden of atrial
      fibrillation, reducing the number of appropriate and inappropriate interventions,
      and adequately predicting heart failure episodes. As in other fields of
      cardiology, technology and innovations for CRT delivery have been at the
      forefront in transforming-improving-patient care; therefore, these innovations
      are discussed in this review.

PMID- 29454550
TI  - Societe d'imagerie musculosquelettique (SIMS), Federation de radiologie
      interventionnelle (FRI), and Societe francaise de radiologie (SFR)
      recommendations for epidural and transforaminal corticosteroid injections.

PMID- 29454552
TI  - Adjustment of the Vocal Tract Shape via Biofeedback: A Case Study.
AB  - In this study, an adjustment of the vocal tract shape toward selected sound waves
      in the frequency range of the first and second formants without phonation is
      discussed. The sound waves of a loudspeaker in front of the open mouth and
      amplified by the vocal tract are used as biofeedback signals. It is shown that
      the resonance amplification of the vocal tract complies with the concept of
      forced oscillation, with the driver being the sound source and the resonator
      being the vocal tract. An adjustment toward increased amplification via vocal
      tract resonance can be related to smaller bandwidths and lower damping.
      Furthermore, the applied adjustment frequencies are preserved as vocal tract
      resonances during exhalation and even phonation. This novel form of biofeedback
      might enrich standard voice training procedures by exercises without phonation.

PMID- 29454551
TI  - Rostral anterior cingulate cortex is a structural correlate of repetitive TMS
      treatment response in depression.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective
      treatment for medication-refractory major depression, yet the mechanisms of
      action for this intervention are poorly understood. Here we investigate cerebral
      cortex thickness as a possible biomarker of rTMS treatment response. METHODS:
      Longitudinal change in cortical thickness is evaluated relative to clinical
      outcomes across 48 participants in 2 cohorts undergoing left dorsolateral
      prefrontal cortex rTMS as a treatment for depression. RESULTS: Our results reveal
      changes in thickness in a region of the left rostral anterior cingulate cortex
      that correlate with clinical response, with this region becoming thicker in
      patients who respond favorably to rTMS and thinner in patients with a less
      favorable response. Moreover, the baseline cortical thickness in this region
      correlates with rTMS treatment response - those patients with thinner cortex
      before treatment tended to have the most clinical improvement. CONCLUSIONS: This
      study is the first analysis of longitudinal cortical thickness change with rTMS
      as a treatment for depression with similar results across two cohorts. These
      results support further investigation into the use of structural MRI as a
      possible biomarker of rTMS treatment response.

PMID- 29454553
TI  - Mapping nutrition and health data in conflict-affected countries.

PMID- 29454554
TI  - Geospatial inequalities and determinants of nutritional status among women and
      children in Afghanistan: an observational study.
AB  - BACKGROUND: Undernutrition is a pervasive condition in Afghanistan, and
      prevalence is among the highest in the world. We aimed to comprehensively assess
      district-level geographical disparities and determinants of nutritional status
      (stunting, wasting, or underweight) among women and children in Afghanistan.
      METHODS: The study used individualised data from the recent Afghanistan National
      Nutrition Survey 2013. Outcome variables were based on growth and weight
      anthropometry data, which we analysed linearly as Z scores and as dichotomous
      categories. We analysed data from a total of almost 14 000 index mother-child
      pairs using Bayesian spatial and generalised least squares regression models
      accounting for the complex survey design. FINDINGS: We noted that childhood
      stunting, underweight, and combined stunting and wasting were consistently
      highest in districts in Farah, Nangarhar, Nuristan, Kunar, Paktia, and Badakhshan
      provinces. District prevalence ranged from 4% to 84% for childhood stunting and
      5% to 66% for underweight. Child wasting exceeded 20% in central and high
      conflict regions that bordered Pakistan including east, southeast, and south.
      Among mothers, dual burden of underweight and overweight or obesity existed in
      districts of north, northeast, central, and central highlands (prevalence of 15
      20%). Linear growth and weight of children were independently associated with
      household wealth, maternal literacy, maternal anthropometry, child age, food
      security, geography, and improved hygiene and sanitation conditions. The mother's
      body-mass index was determined by many of the same factors, in addition to
      ethnolinguistic status and parity. Younger mothers (<20 years old) were more
      underweight and shorter than older mothers (aged 20-49 years). INTERPRETATION:
      Afghanistan's rapidly changing political, socioeconomic, and insecurity landscape
      has both direct and indirect implications on population nutrition. Novel evidence
      from our study can be used to understand these multifactorial determinants and to
      identify granular disparities for local level tracking, planning, and
      implementation of nutritional interventions. FUNDING: None.

PMID- 29454555
TI  - Desire for Patient-Centered HIV Care Among Inconsistently Engaged Racial and
      Ethnic Minority People Living With HIV.
AB  - Many low-income people of color living with HIV are not virally suppressed. More
      research is needed to understand how socially marginalized, disengaged, or
      inconsistently engaged people living with HIV (PLWH) contend with antiretroviral
      therapy (ART)-related challenges, particularly in the context of interactions
      with HIV care providers. Twenty-seven semi-structured interviews were conducted
      with low-income Black and Hispanic PLWH in the New York City area who were
      currently, or recently, disengaged from outpatient HIV health care at the time of
      the interview. Participants valued patient-centered health care in which they
      felt genuinely heard and cared for by their HIV clinicians. This desire was
      particularly pronounced in the context of wanting to change one's ART regimen.
      Participant emphasis on wanting to manage ART-related challenges with their
      providers suggests that HIV providers have an instrumental role in helping their
      patients feel able to manage their HIV.

PMID- 29454556
TI  - Validity and Responsiveness of the Two-Minute Walk Test for Measuring Functional
      Recovery After Total Knee Arthroplasty.
AB  - BACKGROUND: The 2-minute walk test (2mwt) is a performance-based test that
      evaluates functional recovery after total knee arthroplasty (TKA). This study
      evaluated its validity compared with the modified Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), modified Knee
      Score, Numerical Pain Rating Scale, and Timed Up and Go test, and its
      responsiveness in assessing functional recovery in TKA patients. METHODS: This
      prospective cohort study included 162 patients undergoing primary TKA between
      2013 and 2015. We used patient-reported outcome measures (modified WOMAC, OKS,
      modified Knee Score, Numerical Pain Rating Scale) and performance-based tests
      (2mwt and Timed Up and Go test) at baseline and 3, 6, and 12 months
      postoperatively. The construct validity of 2mwt was determined between the 2mwt
      distances walked and other outcome measurements. To assess responsiveness, effect
      size and standardized response mean were analyzed. Minimal clinically important
      difference of 2mwt at 12 months after TKA was also calculated. RESULTS: All
      outcome measurements improved significantly from baseline to 3, 6, and 12 months
      postoperatively. Bivariate analysis revealed mild to moderate associations
      between the 2mwt and modified WOMAC function subscales, and moderate to strong
      associations with OKS. Mild to moderate correlations were found for pain and
      stiffness between 2mwt and other outcome measurements. The effect size and
      standardized response mean at 12 months were large, with a minimal clinically
      important difference of 12.7 m. CONCLUSION: 2mwt is a validated performance-based
      test with responsiveness properties. Being simple and easy to perform, it can be
      used routinely in clinical practice to evaluate functional recovery after TKA.

PMID- 29454557
TI  - Development of a risk-scoring system to evaluate the serosal invasion for
      macroscopic serosal invasion positive gastric cancer patients.
AB  - BACKGROUND: The status of serosal invasion is often discordance between
      pathological and intraoperative evaluation. Our study sought to develop a risk
      scoring system (RSS) to predict the probability of pT4a for macroscopic serosal
      invasion (MSI) positive patients and reevaluate the serosal invasion status.
      PATIENTS AND METHODS: A total of 1301 pT3/pT4a gastric cancer patients with
      curative surgery were reviewed. We constructed the RSS to predict the probability
      of pT4a and assigned MSI-positive patients into different risk groups based on
      the risk scores. The prognostic significance of these risk groups was also
      evaluated. RESULTS: Univariate and multivariate analyses identified that tumor
      location, Lauren type, Borrmann type, tumor size, lymphovascular invasion and pN
      stage were risk factors related to pT4a. Survival analyses showed that pT3 MSI
      positive patients in high-risk group had similar survival with pT4a patients. We
      incorporated these two groups into one stage and proposed a novel revised-T
      stage. Two-step multivariate analyses indicated that the revised-T stage showed
      better prediction ability for prognosis and peritoneal recurrence assessment than
      original pT stage and MSI status. CONCLUSIONS: In our present study, we developed
      a RSS to predict the probability of pT4a for MSI-positive patients. Based on our
      RSS, we proposed a treatment algorithm to reevaluate the tumor invasion for MSI
      positive patients in clinical practice. Future studies should include other
      preoperative predictors to improve the clinical utility of our model.

PMID- 29454558
TI  - Clinical characteristics and management of patients with atrial fibrillation
      treated with direct oral anticoagulants according to blood pressure control.
AB  - OBJECTIVE: To determine the clinical characteristics and management of
      hypertensive patients with nonvalvular atrial fibrillation (AF) treated with
      direct oral anticoagulants (DOACs) according to blood pressure (BP) control.
      METHODS: For this purpose, data from two observational, cross-sectional and
      multicenter studies were combined. In both studies, patients on chronic treatment
      with anticoagulants and that were on current treatment with DOACs at least for 3
      months were included. Adequate BP was defined as a systolic BP<140mmHg and a
      diastolic BP<90mmHg (<140/85mmHg if diabetes). RESULTS: Overall, 1036 patients
      were included. Of these, 881 (85%) had hypertension that were finally analyzed.
      The presence of other risk factors and cardiovascular disease was common. Mean BP
      was 132.6+/-14.3/75.2+/-9.2mmHg and 70.5% of patients achieved BP goals. Those
      patients with a poor BP control had more frequently diabetes, and a history of
      prior labile INR. Patients had a high thromboembolic risk, but without
      significant differences according to BP control. By contrast, more patients with
      a poor BP control had a higher bleeding risk (HAS-BLED >=3: 24.0% vs 35.4%;
      P<0.001). HAS-BLED score was an independent predictor of poor BP control (odds
      ratio 1.435; 95% confidence interval 1.216-1.693; P<0.001). Satisfaction with
      anticoagulant treatment was independent of BP control. CONCLUSIONS: More than two
      thirds of our patients with hypertension and AF anticoagulated with DOACs achieve
      BP targets, what is clearly superior to that reported in the general hypertensive
      population.

PMID- 29454559
TI  - Update on Hereditary Colorectal Cancer: Improving the Clinical Utility of
      Multigene Panel Testing.
AB  - Colorectal cancer (CRC), one of the most common cancers, is a major public health
      issue globally, especially in Westernized countries. Up to 35% of CRCs are
      thought to be due to heritable factors, but currently only 5% to 10% of CRCs are
      attributable to high-risk mutations in known CRC susceptibility genes,
      predominantly the mismatch repair genes (Lynch syndrome) and adenomatous
      polyposis coli gene (APC; familial adenomatous polyposis). In this era of
      precision medicine, high-risk mutation carriers, when identified, can be offered
      various risk management options that prevent cancers and improve survival,
      including risk-reducing medication, screening for early detection, and surgery.
      The practice of clinical genetics is currently transitioning from phenotype
      directed single gene testing to multigene panels, now offered by numerous
      providers. For CRC, the genes included across these panels vary, ranging from
      well established, clinically actionable susceptibility genes with quantified
      magnitude of risk, to genes that lack extensive validation or have less evidence
      of association with CRC and, therefore, have minimal clinical utility. The
      current lack of consensus regarding inclusion of genes in CRC panels presents
      challenges in patient counseling and management, particularly when a variant in a
      less validated gene is identified. Furthermore, there remain considerable
      challenges regarding variant interpretation even for the well established CRC
      susceptibility genes. Ironically though, only through more widespread testing and
      the accumulation of large international data sets will sufficient information be
      generated to (i) enable well powered studies to determine if a gene is associated
      with CRC susceptibility, (ii) to develop better models for variant interpretation
      and (iii) to facilitate clinical translation.

PMID- 29454560
TI  - Bioactive Lipid Mediator Profiles in Human Psoriasis Skin and Blood.
AB  - Psoriasis is a chronic immune-mediated disease that represents a unique model for
      investigating inflammation at local and systemic levels. Bioactive lipid
      mediators (LMs) are potent compounds reported to play a role in the development
      and resolution of inflammation. Currently, it is not known to what extent these
      LMs are involved in psoriasis pathophysiology and related metabolic dysfunction.
      Here, we use targeted and untargeted liquid chromatography-tandem mass
      spectrometry approaches to quantify LMs in skin and peripheral blood from
      psoriasis patients and compared them with those of healthy individuals. Lesional
      psoriasis skin was abundant in arachidonic acid metabolites, as 8-, 12- and 15
      hydroxyeicosatetraenoic acid, compared with adjacent nonlesional and skin from
      healthy individuals. Additionally, a linoleic acid-derived LM, 13
      hydroxyoctadecadienoic acid, was significantly increased compared with healthy
      skin (607.9 ng/g vs. 5.4 ng/g, P = 0.001). These psoriasis skin differences were
      accompanied by plasma decreases in antioxidant markers, including glutathione,
      and impaired lipolysis characterized by lower concentrations of primary and
      secondary bile acids. In conclusion, our study shows that psoriasis skin and
      blood have disease-specific phenotype profiles of bioactive LMs represented by
      omega-6 fatty acid-oxidized derivatives. These findings provide insights into
      psoriasis pathophysiology that could potentially contribute to new biomarkers and
      therapeutics.

PMID- 29454561
TI  - Flexible Neural Hardware Supports Dynamic Computations in Retina.
AB  - The ability of the retina to adapt to changes in mean light intensity and
      contrast is well known. Classically, however, adaptation is thought to affect
      gain but not to change the visual modality encoded by a given type of retinal
      neuron. Recent findings reveal unexpected dynamic properties in mouse retinal
      neurons that challenge this view. Specifically, certain cell types change the
      visual modality they encode with variations in ambient illumination or following
      repetitive visual stimulation. These discoveries demonstrate that computations
      performed by retinal circuits with defined architecture can change with visual
      input. Moreover, they pose a major challenge for central circuits that must
      decode properties of the dynamic visual signal from retinal outputs.

PMID- 29454562
TI  - Long-term functional, subjective and psychological results after single digit
      replantation.
AB  - OBJECTIVE: The aim of this study was to analyse the long-term functional,
      subjective, and psychological results after single-digit replantation. METHODS:
      Thirty cases of digital replantation (14 thumbs, 12 index fingers, 2 middle
      fingers, 1 ring finger, and 1 little finger) in 30 patients (7 females and 23
      males) with a mean age of 44.2 years (20-65 years) were evaluated at the end of a
      mean follow-up time of 36 months (19-50 months). The active range of motion of
      joints, grip and pinch strength, cutaneous sensibility, upper-extremity
      functioning, and subjective satisfaction were determined using the Disability of
      Arm, Shoulder, and Hand (DASH) questionnaire and the Michigan Hand Outcomes
      questionnaire (MHQ). Psychological sequelae, including depression, anxiety, and
      posttraumatic stress disorder (PTSD), were assessed. A correlation analysis among
      variables was also performed. RESULTS: The mean score for the DASH questionnaire
      was 6.6 (range: 0-39.2). The symptom of cold intolerance occurred in 53% of the
      patients. Two patients were diagnosed with depression, and only one patient
      exhibited PTSD. The DASH score had a good statistical correlation with total grip
      strength, pinch grip strength, and static two-point discrimination (S-2PD) (P <
      0.05). Several aspects of the MHQ were also statistically relevant to some or all
      of the three objective results. Furthermore, the grip strength showed significant
      correlation with DASH and most aspects of the MHQ in multivariate logistic
      regression analysis (P < 0.05). CONCLUSION: Total grip strength is the most
      important factor positively related to subjective outcomes. The incidence rates
      of psychological symptoms after digit replantation are very low at long-term
      follow-up. LEVEL OF EVIDENCE: Level IV, therapeutic study.

PMID- 29454564
TI  - Single or double anterior portal shoulder arthroscopy for Bankart repair? That is
      the question.

PMID- 29454563
TI  - Radiological and clinical outcomes of medial approach open reduction by using two
      intervals in developmental dysplasia of the hip.
AB  - OBJECTIVE: To evaluate the midterm clinical and radiological outcomes of the
      medial approach using two intervals for developmental hip dysplasia (DDH).
      METHODS: The study involved 62 hips of 47 patients (41 girls, 6 boys) treated
      with medial approach for DDH from 1999 to 2010. The age of the patients at
      surgery was 18.7 +/- 2.25 months. Follow up of the patients was 11.3 +/- 3.07
      years. The age of the patients at the last follow up was 12.6 +/- 1.74 years.
      According to the Tonnis classification, 13 hips were grade II, 27 hips were grade
      III and 22 hips were grade IV. Patients were evaluated according to Omeroglu
      radiological criteria and modified McKay functional criteria. The presence of
      avascular necrosis (AVN) of the hip was questioned using the KalamchiMacEwen
      classification. RESULTS: Radiologically, forty eight (77%) hips were evaluated as
      "excellent", 8 (13%) hips as "good" and 5 (8%) hips as "fair plus" and 1 (%2) hip
      as "fair minus". Two (3%) patients had type 1 temporary AVN and one (1%) patient
      had type 4 AVN with coxa magna and overgrowth of the greater trochanter.
      According to McKay functional criteria, 56 (90%) hips had "excellent" and 6 (10%)
      had "good" results. Two (3.2%) hips of one patient had to be reoperated with
      Salter osteotomy and femoral shortening + derotation osteotomy. CONCLUSION:
      Medial approach using two separate intervals for tenotomy and capsulotomy does
      not jeopardize the medial circumflex or the femoral vessels and yields
      satisfactory midterm results for children 18 months old with dysplasia of the
      hip. LEVEL OF EVIDENCE: Level IV, therapeutic study.

PMID- 29454565
TI  - Investigation of the biomechanical and histopathological effects of autologous
      conditioned serum on healing of Achilles tendon.
AB  - OBJECTIVE: The aim of this study to evaluate the effects of autologous
      conditioned serum (ACS) on the healing of transected rat Achilles tendons via the
      assessment of biomechanical and histological parameters. METHODS: The study was
      conducted on 45 male Sprague-Dawley rats. Five rats were used as donors for ACS
      preparation. Animals were randomly assigned to the experimental or control group.
      In both groups, the Achilles tendon was cut transversally and then sutured. In
      the placebo control and ACS-treated groups, saline or ACS, respectively, was
      injected into the repair zone three times after surgery. Ten rats from each group
      (ACS group, n = 20; control group, n = 20) were euthanized at days 15 and 30
      after surgery for histopathological (n = 5) and biomechanical (n = 5) testing.
      The histopathological findings were interpreted using the Bonar and Movin scales.
      Tendon remodelling was evaluated via the immunohistochemical staining of collagen
      type 3. Biomechanical effects were assessed by tensile testing. RESULTS: The
      Bonar and Movin scale scores were significantly better in the ACS-treated group
      on both day 15 (p = 0.003 and p = 0.003, respectively) and day 30 (p = 0.005 and
      p = 0.004, respectively). The immunohistochemical density of collagen type 3 was
      significantly lower in the ACS-treated group on day 30 (p = 0.018). The type 1/3
      collagen ratios of the groups were similar on days 15 and 30, as determined by
      Sirius Red staining (p = 0.910 and p = 0.133, respectively). In the biomechanical
      assessment results, the ACS-treated group's maximum load to failure values were
      significantly higher on day 15 (p = 0.049). CONCLUSION: Injection of ACS had a
      positive effect on the histopathological healing of rat Achilles tendons on days
      15 and 30 and on biomechanical healing on day 15. ACS treatment contributed to
      lowering the collagen type 3 density by day 30. According to our study, ACS may
      be favourable for the treatment of human Achilles tendon injuries and
      tendinopathies.

PMID- 29454566
TI  - Determinants of Stroke in Brazil: A Cross-Sectional Multivariate Approach from
      the National Health Survey.
AB  - OBJECTIVE: The objective of this study was to investigate the association between
      biological-health, socioeconomics, and behavioral determinants and stroke by
      evaluating the risk of stroke in the presence of each or all determinants grouped
      in a multivariate model. METHODS: This study is a transversal secondary data
      analysis of the Brazilian National Health Survey, released by the Brazilian
      Institute of Geography and Statistics. The prevalence, prevalence ratios, and
      confidence intervals were calculated for the main outcome. A multivariate
      regression model was applied, with the stroke as outcome and all other variables
      with a P value of .20 or lower in the univariate analysis included as explanatory
      variables to adjust for potential confounders and effect modifiers. RESULTS: The
      mean age was 43.3 +/- 16.6 years, ranging from 18 to 101 years. The prevalence of
      hypertension was 21.4%, and with regard to lifestyle habits, it was observed that
      20.0% had smoked but stopped and 29.7% practiced physical activity in the last 30
      days. The regression model showed that the odds ratio in the final model was
      weighted, with low schooling, smoking habit, overweight, low physical activity
      practice, diabetes, and hypertension being significantly associated with stroke.
      CONCLUSION: The multivariate model showed that the chance of stroke is high, both
      combined or isolated.

PMID- 29454567
TI  - Cilostazol May Decrease Plasma Inflammatory Biomarkers in Patients with Recent
      Small Subcortical Infarcts: A Pilot Study.
AB  - BACKGROUND: The mechanism of progressive neurological deficit in patients with
      recent small subcortical infarcts has not yet been clarified. Inflammatory
      biomarkers and the use of cilostazol may be associated with this phenomenon.
      METHODS: Between May 2013 and April 2014, we evaluated consecutive first-ever
      patients with stroke due to recent small subcortical infarcts within 48 hours of
      onset. We divided patients into 2 groups according to the use of antiplatelet
      agents (cilostazol with or without aspirin versus aspirin alone). Plasma
      biomarkers such as matrix metalloproteinase-9, interleukin-6, high sensitive C
      reactive protein, and amyloid beta precursor protein (APP770, indicating
      endothelial dysfunction) were measured twice: (1) within 24 hours; and (2) 1 week
      after their admission. Multivariable logistic regression analyses were performed
      to identify the variables independently associated with progressive neurological
      deficit and poor functional outcome. RESULTS: We analyzed 41 patients (male:
      63.4%, mean age: 70.8 years). Most of the patients (90%) who were treated with
      cilostazol were concomitantly treated with aspirin. Matrix metalloproteinase-9
      and high sensitive C-reactive protein were higher in patients with progressive
      neurological deficit compared with those without. APP770 were more likely to be
      decreased in cilostazol group compared with aspirin group. Multivariable analyses
      show that traditional risk factors such as age and National Institutes of Health
      Stroke Scale scores were independently associated with both progressive
      neurological deficit and poor functional outcome. CONCLUSIONS: Inflammatory
      biomarkers may be associated with progressive neurological deficit. Early
      initiation of cilostazol may decrease the levels of plasma biomarkers.

PMID- 29454569
TI  - Risk of recurrence following mesh associated incisional hernia repair using the
      retromuscular technique in patients with relevant medical conditions.
AB  - BACKGROUND: Incisional hernia is a common problem following open abdominal
      surgery. Hernia repair in patients with relevant medical conditions is a topic of
      controversy due to the high risk of morbidity and recurrence. We investigated the
      risk of recurrence in patients with relevant medical conditions managed with a
      prosthesis in the retromuscular position. METHODS: A retrospective review of the
      data of patients undergoing midline incisional hernia repair was performed. The
      outcomes of patients with relevant concomitant medical conditions defined as ASA
      scores >2 were compared with those of healthier patients with ASA scores <=2.
      RESULTS: 115 patients including 41 with ASA >2 and 74 with ASA <=2 were included
      for analysis. There were no statistically significant differences amongst both
      groups with regard to the size of the hernia defect, the duration of surgery
      (123.0 +/- 71 vs. 149.0 +/- 92 min, p = 0.73), the incidence of postoperative
      seroma (14.6% vs. 29.7%, p = 0.07), postoperative hematoma (12.2% vs. 4.1%, p =
      0.10) and surgical site infection (14.6% vs. 8.1%, p = 0.27). No statistically
      significant difference was seen amongst both groups with respect to the rate of
      long-term recurrence after a median follow-up of 63.0 +/- 36 months (12.2% vs.
      6.8%, p = 0.32). CONCLUSION: Relevant medical condition alone cannot be seen as a
      contraindication for midline incisional hernia repair using the retromuscular
      technique. Rates of morbidity and long-term recurrence following mesh-associated
      closure are not difference from those of healthier patients.

PMID- 29454568
TI  - Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family
      with early-onset disease.
AB  - BACKGROUND AND AIMS: The time course for the development of clinically
      significant hereditary diffuse gastric cancer (HDGC) is unpredictable. Little is
      known about the progression from preclinical, indolent lesions to widely
      invasive, aggressive phenotypes. Gastroendoscopy often fails to detect early
      lesions, and risk-reducing/prophylactic total gastrectomy (PTG) is the only
      curative approach. We present an HDGC family with early-onset disease in which
      clinical and histologic findings provided insight into the understanding of
      different HDGC phenotypes. METHODS: The proband was diagnosed at age 18 years
      with widely invasive, metastatic DGC. CDH1 genetic testing identified a
      pathogenic, germline CDH1 variant (c.1901C>T, p.Ala634Val). Thirty family members
      were tested, and 15 CDH1 carriers were identified. RESULTS: Six family members
      had PTG, with negative preoperative workup. The proband's 14-year-old sister is
      the youngest patient, reported to date, to have PTG after negative preoperative
      biopsy sampling. Intramucosal HDGC foci were detected in all PTG specimens (1
      33). In contrast to the "indolent" phenotype of these foci, the aggressive DGC
      from the proband showed pleomorphic cells, absent E-cadherin expression,
      increased proliferation (Ki-67 index), and activation of oncogenic events (p53,
      pSrc and pStat3 overexpression). All family members had Helicobacter pylori
      gastritis. Cag-A-positive strains were detected in all specimens, except in the
      proband's sister. CONCLUSIONS: HDGC is a heterogeneous disease regarding clinical
      behavior, endoscopic findings, histopathologic features, and
      immunophenotypic/molecular profile. The presence of bizarre, pleomorphic cells in
      endoscopic biopsy specimens is suggestive of advanced disease and should prompt
      clinical intervention. The involvement of a full multidisciplinary team is
      essential for the management of these patients.

PMID- 29454570
TI  - Fibrosis score impacts survival following resection for hepatocellular carcinoma
      (HCC): A Surveillance, End Results and Epidemiology (SEER) database analysis.
AB  - BACKGROUND/OBJECTIVES: Surgical extirpation for hepatocellular carcinoma (HCC)
      with background fibrosis remains a challenge. This study evaluated impact of
      fibrosis score on long term outcomes of patients undergoing surgical resection
      for HCC. METHODS: Using the Surveillance, Epidemiology and End Results (SEER)
      database (2004-2013), complete data on 1433 patients undergoing surgical
      resection for non-metastatic HCC were identified. Overall survival (OS) was
      estimated using the Kaplan-Meier method. Cox proportional hazards model were used
      to produce adjusted hazard ratios (HR). RESULTS: In this study, 54% (650/1433)
      patients had F5-6 fibrosis at the time for surgical resection of HCC. In adjusted
      models, F5/6 fibrosis significantly reduces overall survival (HR: 1.62, 95% CI:
      1.34-1.94; p < 0.001). Median survival was significantly longer for patients with
      F0-4 fibrosis for T1a, T1b and T2 tumours as compared to F5-6 fibrosis, not for
      T3 and T4 tumours, even when stratified by extent of hepatectomy. There were no
      significant differences in 90-day post-operative mortality between fibrosis
      groups when stratified by T-classifications. CONCLUSION: Liver resection in
      patients with advanced fibrosis has significantly lower survival as compared to
      patients with F0-4 fibrosis in early stage (T1 and T2), not advanced tumours (T3
      and T4). Improvement in patient selection and perioperative care for liver
      resection may offer consistent and clinically meaningful long-term survival in
      HCC.

PMID- 29454571
TI  - Feasibility of restorative proctocolectomy in patients with ulcerative colitis
      associated lower rectal cancer: A retrospective study.
AB  - BACKGROUND/OBJECTIVE: Restorative proctocolectomy (RP) may improve quality of
      life in patients with ulcerative colitis (UC)-associated lower rectal cancer to a
      greater extent than total proctocolectomy. However, patients with UC-associated
      cancer often have flat mucosal lesions that make it extremely difficult to
      endoscopically delineate the tumor margins. Therefore, there is a potential risk
      of residual tumor and local recurrence after RP in patients with UC-associated
      lower rectal cancer. The aim of this study was to assess the feasibility of RP in
      patients with UC-associated cancer of the lower rectum. METHODS: We
      retrospectively identified nine patients who had undergone RP for UC-associated
      lower rectal cancer at the Niigata University Medical and Dental Hospital between
      January 2000 and December 2016. The incidence of flat mucosal cancer, distal
      margin status, and oncologic outcomes were evaluated in the nine patients.
      RESULTS: Eight (89%) of the nine patients had flat mucosal cancer in the lower
      rectum. The median length of the distal margin was 22 mm (range 0-55 mm). No
      patient developed local or distant recurrence during follow-up. One patient had a
      positive distal margin. This patient underwent annual pouchoscopy, but had no
      local recurrence and died of pancreatic cancer 81 months after RP. The remaining
      eight patients were alive at the final observation. Five-year and 10-year overall
      survival rates in the nine patients were 100% and 66.7%, respectively.
      CONCLUSION: Patients with UC-associated lower rectal cancer often have lesions of
      the flat mucosal type. However, RP is feasible and not necessarily
      contraindicated in such patients.

PMID- 29454572
TI  - Presence of colon carcinoma cells at the resection line may cause recurrence
      following stapling anastomosis.
AB  - BACKGROUND/OBJECTIVE: The presence of carcinoma cells in the suture line may
      result in local recurrence. The purpose of this study was to assess whether
      carcinoma cells were present along the resection line where the distal clamp was
      applied. METHODS: During surgery, the rectum was clamped at least 3 cm distal to
      the palpable margin of the tumor mass. The rectum was divided distal and proximal
      to the clamp. The tissue inside the clamp was rinsed with normal saline, and the
      irrigation solution was sent for cytologic examination. RESULTS: In 134 patients
      with carcinoma of the rectosigmoid colon or rectum, we found four (3.0%) cases of
      positive cytology, and five cases (3.7%) with cytology indicting the presence of
      atypical cells highly suspicious for malignancy. It was postulated that the
      trapping of cancer cells in a double-staple anastomosis line may have resulted in
      local recurrence. CONCLUSION: This study indicates that double staple-line
      recurrence is related to the shedding of cancer cells during dissection and
      clamping.

PMID- 29454573
TI  - Revisiting donor risk over two decades of single-center experience: More
      attention on the impact of overweight.
AB  - OBJECTIVE: Morbidity rates after living donor hepatectomy vary greatly among
      centers. Donor morbidity in a tertiary center over the past two decades was
      revisited. METHODS: Clinical data and grading of complications were reviewed by a
      nontransplant surgeon based on Clavien 5 tier grading. Risk factors were
      analyzed. RESULTS: In total, 473 consecutive living liver donors from 1997 to
      2016 were included for analysis; 305 were right liver donors and 168 left liver
      donors, and the corresponding morbidity rates were 27.2% and 9.5%. The majority
      (81/99, 81.2%) of complications were grade I and II. Donors with morbidity
      compared with those without were significantly younger, nonoverweight body figure
      (BMI < 25), more as the right liver donors, and longer length of hospital stay.
      Right liver donation had significantly higher morbidity rates than did left liver
      donation in earlier periods (before 2011), but not thereafter. Multivariate
      modeling revealed that right lobe donation and overweight (BMI >= 25 kg/m2) were
      significant factors associated with donor morbidity, with adjusted hazard ratios
      HR (95% confidence interval) of 3.401 (1.909-6.060) and 0.550 (0.304-0.996),
      respectively. Further, overweight was a paradoxical risk factor in right donor
      hepatectomy with HR 0.422 (0.209-0.851), but the effect was nonsignificant in
      left liver donors. Most complications in overweight donors were grade I and not
      specific to liver surgery. CONCLUSIONS: The overall complication rate was 20.9%.
      Overweight might be protective against morbidity in right hepatectomy and
      warrants further deliberation.

PMID- 29454574
TI  - Editorial commentary: Use of cerebral embolic protection devices during
      transcatheter aortic valve replacement.

PMID- 29454576
TI  - Janus face of complement-driven neutrophil activation during sepsis.
AB  - During local and systemic inflammation, the complement system and neutrophil
      granulocytes are activated not only by pathogens, but also by released endogenous
      danger signals. It is recognized increasingly that complement-mediated neutrophil
      activation plays an ambivalent role in sepsis pathophysiology. According to the
      current definition, the onset of organ dysfunction is a hallmark of sepsis. The
      preceding organ damage can be caused by excessive complement activation and
      neutrophil actions against the host, resulting in bystander injury of healthy
      tissue. However, in contrast, persistent and overwhelming inflammation also leads
      to a reduction in neutrophil responsiveness as well as complement components and
      thus may render patients at enhanced risk of spreading infection. This review
      provides an overview on the molecular and cellular processes that link complement
      with the two-faced functional alterations of neutrophils in sepsis. Finally, we
      describe novel tools to modulate this interplay beneficially in order to improve
      outcome.

PMID- 29454577
TI  - Morphological clues to the appropriate recognition of hereditary renal neoplasms.
AB  - An important emerging role of the surgical pathologist besides the traditional
      tasks of establishment of the diagnosis and documentation of prognostic and
      predictive factors, is to recognize the possibility of a hereditary condition in
      cases where the histology is suggestive for a familial cancer syndrome. In recent
      years, the knowledge regarding all of the above roles, including the role of
      recognition of familial cancer, has particularly expanded in renal neoplasms with
      the close scrutiny to morphology, molecular correlates and clinical features of
      the different sub-types of renal cell carcinoma. Awareness of these clinically
      distinctive sub-types and their associated histologic clues will prompt the
      pathologist for further immunohistochemical or molecular work up, to look for
      clinical information to support the suspected diagnosis of familial cancer, to
      alert managing physician/s to look for stigmata of history of familial cancer,
      which will permit triaging patients and their families for appropriate genetic
      counseling. This review provides a comprehensive review of the known sub-types of
      renal cell carcinoma that have a predilection to occur in the setting of
      hereditary disease; examples include renal cancers occurring in the background of
      von Hippel Lindau disease, hereditary leiomyomatosis and renal cell carcinoma
      syndrome, tuberous sclerosis, Birt Hogg Dube syndrome and succinate dehydrogenase
      deficiency. Herein we focus on diagnostic clues for renal tumors occurring in a
      non-pediatric setting that should prompt their correct recognition and reiterate
      the importance of the correct diagnosis.

PMID- 29454578
TI  - Arithmetic skills correlate negatively with the overlap of symbolic and non
      symbolic number representations in the brain.

PMID- 29454575
TI  - Targeting complement-mediated immunoregulation for cancer immunotherapy.
AB  - Complement was initially discovered as an assembly of plasma proteins
      "complementing" the cytolytic activity of antibodies. However, our current
      knowledge places this complex system of several plasma proteins, receptors, and
      regulators in the center of innate immunity as a bridge between the initial
      innate responses and adaptive immune reactions. Consequently, complement appears
      to be pivotal for elimination of pathogens, not only as an early response
      defense, but by directing the subsequent adaptive immune response. The discovery
      of functional intracellular complement and its roles in cellular metabolism
      opened novel avenues for research and potential therapeutic implications. The
      recent studies demonstrating immunoregulatory functions of complement in the
      tumor microenvironment and the premetastatic niche shifted the paradigm on our
      understanding of functions of the complement system in regulating immunity.
      Several complement proteins, through their interaction with cells in the tumor
      microenvironment and in metastasis-targeted organs, contribute to modulating
      tumor growth, antitumor immunity, angiogenesis, and therefore, the overall
      progression of malignancy and, perhaps, responsiveness of cancer to different
      therapies. Here, we focus on recent progress in our understanding of
      immunostimulatory vs. immunoregulatory functions of complement and potential
      applications of these findings to the design of novel therapies for cancer
      patients.

PMID- 29454580
TI  - Are synechiae a complication of laparotomic myomectomy?
AB  - Laparotomic myomectomy is often the only realistic solution for symptomatic women
      with multiple or large myomas who wish to retain their fertility. The aim of this
      study was to document the rate of uterine synechiae and their associated risk
      factors after laparotomic myomectomy. This prospective observational study took
      place in a teaching hospital from May 2009 to June 2014. It included all women
      aged 18-45 years who had laparotomic myomectomies (without diagnostic
      hysteroscopy at the time of surgery) for myomas and a postoperative diagnostic
      office hysteroscopy 6-8 weeks later. The study included 98 women with a
      laparotomic myomectomy and a postoperative hysteroscopic follow-up. Women with a
      laparotomic myomectomy for a subserosal myoma were excluded. The intrauterine
      adhesion rate after laparotomic myomectomy was 25.51% (25/98); 44% (11/25) of
      them were complex intrauterine adhesions. Opening the uterine cavity was a major
      risk factor for these complex adhesions, with an OR of 6.42 (95% CI 1.27 to
      32.52). Office hysteroscopy could be carried out after surgery in such cases.

PMID- 29454579
TI  - Nucleus accumbens inflammation mediates anxiodepressive behavior and compulsive
      sucrose seeking elicited by saturated dietary fat.
AB  - OBJECTIVE: The incidence of depression is significantly compounded by obesity.
      Obesity arising from excessive intake of high-fat food provokes anxiodepressive
      behavior and elicits molecular adaptations in the nucleus accumbens (NAc), a
      region well-implicated in the hedonic deficits associated with depression and in
      the control of food-motivated behavior. To determine the etiology of diet-induced
      depression, we studied the impact of different dietary lipids on anxiodepressive
      behavior and metabolic and immune outcomes and the contribution of NAc immune
      activity. METHODS: Adult C57Bl/6 mice were subjected to isocaloric high-fat/high
      sucrose diets (HFD), enriched in either saturated or monounsaturated fat, or a
      control low-fat diet (LFD). Metabolic responses, anxiodepressive behavior, and
      plasma and NAc inflammatory markers were assessed after 12 weeks. In separate
      experiments, an adenoviral construct inhibiting IKKbeta, an upstream component of
      the nuclear factor kappa-b (NFkB) pathway, was a priori injected into the NAc.
      RESULTS: Both HFDs resulted in obesity and hyperleptinemia; however, the
      saturated HFD uniquely triggered anxiety-like behavior, behavioral despair,
      hyperinsulinemia, glucose intolerance, peripheral inflammation, and multiple pro
      inflammatory signs in the NAc, including reactive gliosis, increased expression
      of cytokines, antigen-presenting markers and NFkB transcriptional activity.
      Selective NAc IKKbeta inhibition reversed the upregulated expression of
      inflammatory markers, prevented anxiodepressive behavior and blunted compulsive
      sucrose-seeking in mice fed the saturated HFD. CONCLUSIONS: Metabolic
      inflammation and NFkB-mediated neuroinflammatory responses in the NAc contribute
      to the expression of anxiodepressive behavior and heightened food cravings caused
      by a diet high in saturated fat and sugar.

PMID- 29454581
TI  - Emerging roles of microglial cathepsins in neurodegenerative disease.
AB  - Alzheimer's disease (AD) is one of the leading causes of dementia, and its
      prevalence is expected to increase dramatically due to the aging global
      population. Microglia-driven neuroinflammation may contribute to the progression
      of AD. Microglia, the immune cells of the central nervous system (CNS), become
      chronically activated by the pathological proteins of AD including amyloid-beta
      peptides (Abeta). Such adversely activated microglia secrete mediators that
      promote inflammation and damage neurons. Cathepsins are proteases that are
      expressed by all brain cell types, and most of them are found both intra- and
      extra-cellularly. Microglia express and secrete several different cathepsins,
      which support various immune functions of microglia, in addition to their
      involvement in key neuroinflammatory pathways. This review focuses specifically
      on microglial cathepsins B, D and S, which have been implicated in AD
      pathogenesis; we identify their roles relevant to microglial involvement in AD
      pathogenesis. As dysregulated microglial function and neuroinflammation can
      contribute to AD progression, cathepsins should be considered as potential
      therapeutic targets for the development of effective AD treatment options. We
      conclude that the specific inhibition of microglial cathepsin B may lead to
      neuroprotective outcomes in AD, while the functions of this cysteine protease in
      neurons appears to be very complex and further studies are required to fully
      elucidate the pathophysiological role of neuronal cathepsin B. Examination of the
      CNS roles of cathepsins is limited by the shortage of highly selective
      inhibitors, with CA-074 being the only available specific cathepsin B inhibitor.
      We also conclude that non-specific inhibition of aspartic proteases, including
      cathepsin D, may promote adverse CNS effects, and may not be safe as AD
      therapeutics. Finally, cathepsin S inhibition has shown promise in preclinical
      studies due to its neuroprotective and anti-inflammatory effects; however, the
      many homeostatic roles of cathepsin S must be considered during the subsequent
      stages of development of cathepsin S inhibitors as AD therapeutics. Discovery of
      novel, highly selective inhibitors of various cathepsins and their clinical
      testing are required for the development of effective future AD therapies.

PMID- 29454582
TI  - Predictors and Outcomes of Cardiac Surgery-Associated Delirium. A Single Centre
      Retrospective Cohort Study.
AB  - BACKGROUND: The predictors and independent outcome association of delirium after
      cardiac surgery are important and yet poorly characterised. METHODS: We performed
      a retrospective observational study of cardiac surgery patients between January
      2009 and March 2016. We defined delirium using ICD-10 diagnostic codes.
      Multivariable analysis was conducted to find independent associations between
      baseline variables, delirium, and key clinical outcomes. RESULTS: We studied 2447
      study patients (28.7% female, median age was 66 [IQR 57-74] years). Delirium was
      coded for in 12.9% of patients overall, and in 22.9% of those aged >75years.
      Increasing age, Charlson co-morbidity index, admission not from home, peripheral
      vascular disease, respiratory disease, preoperative atrial fibrillation, duration
      of cardiopulmonary bypass and nature of surgery were all independent predictors
      of delirium. Delirium was independently and strongly associated with increased
      risk of reintubation (OR 8.18 [95% CI 5.24-12.78]), tracheostomy (OR 10.44 [95%
      CI 5.91-18.45]), and increased length of stay by 113.7 [95% CI 99.7-127.7] ICU
      hours and 6.95 [95% CI 5.94-7.95] hospital days, but not 30-day mortality (OR
      0.78 [95% CI 0.38-1.59]; p=0.5). CONCLUSIONS: Delirium is common in cardiac
      surgery patients and increases with age. Delirium was the strongest predictor of
      reintubation, need for tracheostomy, and prolongation of intensive care unit
      (ICU) and hospital length of stay. Delirium prevention and attenuation are a
      priority in cardiac surgery patients.

PMID- 29454583
TI  - Post-operative ventricular flow dynamics following atrioventricular valve
      surgical and device therapies: A review.
AB  - Intra-ventricular flow dynamics has recently emerged as an important evaluation
      and diagnosis tool in different cardiovascular conditions. The formation of
      vortex pattern during the cardiac cycle has been suggested to play important
      epigenetic and energy-modulation roles in cardiac remodelling, adaptations and
      mal-adaptations. In this new perspective, flow alterations due to different
      cardiovascular procedures can affect the long-term outcome of those procedures.
      Especially, repairs and replacements performed on atrioventricular valves are
      likely to exert direct impact on intra-ventricular flow pattern. In this review,
      current consensus around the roles of vortex dynamics in cardiac function is
      discussed. An overview of physiological vortex patterns found in healthy left and
      right ventricles as well as post-operative ventricular flow phenomenon owing to
      different atrioventricular valvular procedures are reviewed, followed by the
      summary of different vortex identification schemes used to characterise
      intraventricular flow. This paper also emphasises on future research directions
      towards a comprehensive understanding of intra-cardiac flow and its clinical
      relevance. The knowledge could encourage more effective pre-operative planning
      and better outcomes for current clinical practices.

PMID- 29454584
TI  - Fat-specific protein 27 is a novel target gene of liver X receptor alpha.
AB  - Fat-specific protein 27 (FSP27) is highly expressed in the fatty liver of
      genetically obese ob/ob mice and promotes hepatic triglyceride (TG) accumulation.
      The nuclear hormone receptor liver X receptor alpha (LXRalpha) also plays a
      critical role in the control of TG levels in the liver. The present study
      demonstrated transcriptional regulation of Fsp27a and Fsp27b genes by LXRalpha.
      Treatment with the LXR ligand T0901317 markedly increased Fsp27a and Fsp27b mRNAs
      in wild-type C57BL/6J and ob/ob mouse livers. A reporter assay indicated that two
      LXR-responsive elements (LXREs) are necessary for LXRalpha-dependent induction of
      Fsp27a and Fsp27b promoter activities. Furthermore, the LXRalpha/retinoid X
      receptor alpha complex is capable of directly binding to the two LXREs both in
      vitro and in vivo. These results suggest that LXRalpha positively regulates
      Fsp27a and Fsp27b expression through two functional LXREs. Fsp27a/b are novel LXR
      target genes in the ob/ob fatty liver.

PMID- 29454585
TI  - The hot cross bun sign in a patient with encephalitis.
AB  - The 'hot cross' bun (HCB) sign refers to pontine cruciform hyperintensity on T2
      weighted magnetic resonance image (MRI) which is frequently seen in multiple
      system atrophy and spinocerebellar ataxia types 2 and 3. We describe a 3 years
      old boy of encephalitis and his MRI image showed HCB sign in the pontine. After
      immunosuppressive treatment and followed up 14 months, he got a good outcome and
      the HCB sign narrowed nearly disappeared.

PMID- 29454587
TI  - Comparison of CT radiogenomic and clinical characteristics between EGFR and KRAS
      mutations in lung adenocarcinomas.
AB  - AIM: To compare computed tomography (CT) radiogenomic and clinical
      characteristics between patients with epidermal growth factor receptor (EGFR) and
      Kirsten rat sarcoma viral oncogene (KRAS) mutations in lung adenocarcinomas.
      MATERIALS AND METHODS: This study was a retrospective analysis of patients with
      histopathologically confirmed lung adenocarcinoma, who had complete clinical and
      imaging data, and were tested for EGFR and KRAS mutations. Of the 313 included
      patients, 116 had effective EGFR mutations (EGFR group), 31 had KRAS mutations
      (KRAS group), and 166 had no EGFR or KRAS mutations (control group). Multivariate
      analysis was used to evaluate CT imaging features and clinical data. RESULTS:
      Multivariate analysis showed that significant variables between the EGFR and
      control groups were spiculation (odds ratio [OR] 2.70, 95% confidence interval
      [CI]: 1.54-4.75, p=0.001), and multiple small metastatic nodules (OR=7.52, 95%
      CI: 1.44-39.17, p=0.017). Significant variables between the KRAS and the control
      group were multiple small metastatic nodules (OR=7.65, 95% CI: 1.18-49.50,
      p=0.033). CONCLUSIONS: Patients with EGFR or KRAS mutations are prone to multiple
      metastases in both lungs. In addition, effective EGFR mutations mostly occurred
      in patients with multiple spiculations.

PMID- 29454586
TI  - Isolation of two plasmids, pRET1100 and pRET1200, from Rhodococcus erythropolis
      IAM1400 and construction of a Rhodococcus-Escherichia coli shuttle vector.
AB  - With the aim of being able to co-express multiple genes, I searched for novel
      compatible plasmids and isolated two plasmid species, pRET1100 and pRET1200, from
      Rhodococcus erythropolis IAM1400. Sequencing analysis revealed that the pRET1100
      plasmid is a double-stranded DNA molecule of 5444 bp with two possible open
      reading frames (ORFs), repT and div, and three minor ORFs. The cryptic
      replication protein, RepT, is not highly homologous to those from other plasmids
      that have been reported. The Rhodococcus-Escherichia coli shuttle vector pRET1102
      was transformed into R. erythropolis JCM2895 harboring the pRE2895 plasmid. The
      recombinant R. erythropolis JCM2895 harbored two plasmid species. These results
      suggest that plasmid derivatives of pRET1100 and pRE2895 are fully compatible in
      R. erythropolis. I determined the minimum region of pRET1100 required for
      autonomous replication in R. erythropolis and constructed a high-copy plasmid,
      pRET1129, in R. erythropolis.

PMID- 29454588
TI  - Diagnostic performance of two corrected transluminal attenuation gradient metrics
      in coronary CT angiography for the evaluation of significant in-stent restenosis
      by dual-source CT: a validation study with invasive coronary angiography.
AB  - AIM: To determine the diagnostic potential of transluminal attenuation gradients
      (TAG) with exclusion of stented coronary segments (TAG-ExS) and TAG-corrected
      contrast opacification (CCO) excluding stented coronary segments (TAG-CCO-ExS)
      for the assessment of in-stent restenosis (ISR). MATERIALS AND METHODS: TAG-ExS
      and TAG-CCO-ExS were calculated in 93 coronary arteries with 190 stents. The
      diagnostic performances and the incremental values of the two metrics to coronary
      computed tomography angiography (CCTA) were analysed and compared. RESULTS: For
      all stents and stents >3 mm in diameter, TAG-ExS and TAG-CCO-ExS were
      significantly lower in >=50% than that in <50% of ISR (both p<0.05). For stent
      diameters <=3 mm, significantly lower TAG-CCO-ExS (p=0.000), but not TAG-ExS
      (p=0.059), was found in >=50% than in <50% of ISR. Addition of TAG-ExS or TAG-CCO
      ExS to CCTA, did not improve the diagnostic accuracy of CCTA significantly (all
      p>0.05). Only TAG-CCO-ExS had a significant impact on CCTA for the
      reclassifications of ISR (p=0.046) in stent diameters <=3 mm. CONCLUSIONS: TAG
      ExS and TAG-CCO-ExS did not provide incremental diagnostic value over CCTA in
      assessing ISR. TAG-CCO-ExS slightly enhanced the reclassifications of ISR for
      stents <=3 mm in diameter.

PMID- 29454589
TI  - A retrospective review of registrar out-of-hours reporting in a university
      hospital: the effect of time and seniority on discrepancy rates.
AB  - AIM: To assess the influence of time, intensity, and trainee seniority on
      radiology registrars' major and minor discrepancy rates during weekend reporting
      at a university teaching hospital. MATERIALS AND METHODS: A 12-month
      retrospective review was performed of out-of-hours trainee provisional reports
      for computed tomography (CT) and magnetic resonance imaging (MRI) in a university
      teaching hospital. From Friday 9.00 pm to Sunday 9.00 pm, the out-of-hours
      service is provided by a single registrar rotating every 12 hours. A busy shift
      was defined as more than 24 reports issued during the shift. A senior trainee was
      defined as having more than 2 years' experience on the on-call rota. Reports were
      compared to subsequent subspecialist consultant review with all discrepancies
      collected. Discrepancy rates were calculated for junior/senior registrars, time
      of shift, and for busy/less busy shifts. RESULTS: The total discrepancy rate was
      11.1%, with a major discrepancy rate of 3%. Junior registrars had a lower total
      discrepancy rate (9.7% versus 12.2%, p=0.0065). Although there was no difference
      between major discrepancies, junior trainees made fewer minor discrepancies (7.1%
      versus 8.93%, p=0.03). The discrepancy rate was higher at night (12.3% versus
      10.4%, p=0.0418). On a less busy shift, more discrepancies were made (12.8%
      versus 10%, p=0.0001). CONCLUSION: The major discrepancy rate of trainees is low.
      More discrepancies are made at night, and trainee seniority does not mitigate
      this problem. Night shifts are less busy in comparison to day shifts, which may
      explain why less busy shifts appear to yield more mistakes.

PMID- 29454590
TI  - Understanding how prostate cancer patients value the current treatment options
      for metastatic castration resistant prostate cancer.
AB  - : Several new compounds are now available for castration resistant prostate
      cancer (CRPC). Individual costs range between $40,000 and $93,000 with mean
      survival extensions from 2.4 to 4.8 months. Currently, it remains unclear how
      patients with prostate cancer (PCa) value the effect of these therapies in the
      setting of CRPC. OBJECTIVE: To assess patient understanding of core cancer
      concepts, opinions on the cost and overall benefit of CRPC drugs, whether out-of
      pocket costs would change opinions and whether patients would ultimately opt out
      of CRPC drug treatment for an end-of-life (EOL) premium. PATIENTS AND METHODS: We
      conducted a qualitative survey among patients with various PCa states ranging
      from active surveillance to CRPC and from various familial, financial and
      educational demographics. Through a series of hypothetical scenarios, we
      extrapolated opinions on CRPC drug value, efficacy and monetary worth. We
      assessed patient willingness to accept an EOL ($50,000) premium in lieu of CRPC
      drug treatment. Statistically, chi-squared analysis and Fisher's exact test were
      used when appropriate. RESULTS: In total, 103 patients completed the
      questionnaire, one-half of whom did not understand "advanced PCa" state and more
      than one-third of the concept of palliative care despite multiple meetings with
      Urologists. Patients willingness-to-pay and proposed drug value was higher than
      that accepted by government when government funded, with costs exceeding $250,000
      per person, but lower than that accepted by government when self-funded. A
      majority (60%) would accept/consider the EOL premium in the setting of CRPC.
      Patients with higher education were more skeptical about CRPC drug value and more
      likely to accept the EOL premium (P = 0.003.) CONCLUSION: Patients have an
      incomplete understanding of their own disease prognosis and its therapeutic
      options. This ultimately influences patient decision-making. Education, income
      and out-of-pocket costs diminished opinion of CRPC drugs considerably. As such,
      an EOL premium should be considered in subsets of patients.

PMID- 29454591
TI  - The effect of treatment at minority-serving hospitals on outcomes for bladder
      cancer.
AB  - OBJECTIVES: Healthcare for racial minorities is densely concentrated at a small
      subset of hospitals in the United States. Understanding long-term outcomes at
      these minority-serving hospitals is highly relevant to elucidating the sources of
      racial disparities in cancer care. We investigated the effect of treatment at a
      minority-serving hospital on overall survival and receipt of definitive treatment
      for bladder cancer. MATERIALS AND METHODS: Using the National Cancer Database, we
      identified all patients diagnosed with clinically localized, muscle-invasive
      bladder cancer between 2004 and 2012. We defined "minority-serving hospitals" as
      institutions in the top decile by proportion of Black and Hispanic patients
      within this cohort. Univariate and multivariable analyses were performed to
      assess the sociodemographic, clinical, and hospital-level factors influencing
      overall survival and receipt of definitive treatment for bladder cancer. RESULTS:
      In adjusted analyses, there was no significant difference in overall survival
      between patients treated at minority-serving hospitals versus those treated at
      nonminority-serving hospitals (hazard ratio = 0.95, 95% CI: 0.90-1.01). There was
      also no significance in receipt of definitive treatment between the two hospital
      types (odds ratio [OR] = 0.85, 95% CI: 0.68-1.06). Black race was independently
      associated with increased likelihood of mortality (hazard ratio = 1.08, 95% CI:
      1.03-1.14) and decreased odds of receiving appropriate definitive treatment (OR =
      0.73, 95% CI: 0.66-0.82). CONCLUSIONS: There was no difference between minority
      serving and nonminority-serving hospitals in overall survival or receipt of
      definitive treatment. Black patients suffered worse survival and were less likely
      to receive definitive treatment for bladder cancer regardless of the type of
      hospital in which they were treated.

PMID- 29454592
TI  - Effective Antimicrobial Stewardship Strategies for Cost-effective Utilization of
      Telavancin for the Treatment of Patients With Hospital-acquired Bacterial
      Pneumonia Caused by Staphylococcus aureus.
AB  - PURPOSE: Clinicians and stewardship programs are challenged with positioning of
      novel, higher priced antibiotic agents for the treatment of clinical infections.
      We developed a decision-analytic model to describe costs, including drug, total
      treatment costs, and health care outcomes, associated with telavancin (TLV)
      compared with vancomycin (VAN) for patients with Staphylococcus aureus (SA)
      hospital-acquired bacterial pneumonia (HABP). METHODS: This decision-analytic
      model assessed the treatment of SA-HABP with TLV versus VAN. Data were obtained
      from the ATTAIN (Assessment of Telavancin for Treatment of Hospital-Acquired
      Pneumonia) clinical trials on the following: the probability of clinical cure;
      probability of nephrotoxicity; and prevalence of polymicrobial infection (30%),
      methicillin-resistant Staphylococcus aureus (MRSA) (68%), and SA with VAN MIC >=1
      ug/mL (85%). Data on length of stay for cure (10 days), failure (10 additional
      days), and nephrotoxicity (3.5 days) were based on literature. Cost per treated
      patient and incremental cost-effectiveness ratio (ICER) per additional cure were
      calculated for SA-HABP and for monomicrobial SA-HABP. One-way sensitivity
      analyses were performed. FINDINGS: Patients with SA-HABP were sub-grouped by
      methicillin susceptibility (n = 140, 32%) or resistance (n = 293, 68%), and
      occurrence of polymicrobial (n = 128, 30%) vs monomicrobial (n = 305, 70%)
      infections. Under the base case, hospital cost for patients with HABP treated
      with TLV was $42,564 and with VAN, it was $42,296. Telavancin was associated with
      higher drug ($2082) and nephrotoxicity ($467) costs and lower intensive care unit
      (-$1738) and ventilator (-$114) costs. ICER was $4156 per additional cure. ICER
      was sensitive to probabilities of cure, length of treatment in cures, intensive
      care unit cost, TLV cost, and additional length of stay due to failure. For
      monomicrobial SA-HABP, TLV was associated with a net cost savings of $907 per
      patient and yielded economic dominance. IMPLICATIONS: Our decision-analytic model
      suggests that TLV for monomicrobial SA-HABP is associated with higher drug
      acquisition costs but a favorable ICER relative to VAN, provided that effective
      antimicrobial stewardship limits therapy to 7 days. Sensitivity analyses suggest
      a potential economic benefit of TLV treatment with appropriate patient selection.
      Antimicrobial stewardship programs may be able to reduce total costs through
      judicious use of novel antimicrobial agents. ClinicalTrials.gov identifiers:
      NCT00107952 and NCT00124020.

PMID- 29454593
TI  - Department of Error.

PMID- 29454594
TI  - Low magnesium intake is associated with increased knee pain in subjects with
      radiographic knee osteoarthritis: data from the Osteoarthritis Initiative.
AB  - OBJECTIVE: As magnesium mediates bone and muscle metabolism, inflammation, and
      pain signaling, we aimed to evaluate whether magnesium intake is associated with
      knee pain and function in radiographic knee osteoarthritis (OA). METHODS: We
      investigated the associations between knee pain/function metrics and magnesium
      intake from food and supplements in 2548 Osteoarthritis Initiative cohort
      participants with prevalent radiographic knee OA (Kellgren-Lawrence score >=2).
      Magnesium intake was assessed by Food Frequency Questionnaire (FFQ) at baseline.
      WOMAC and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were
      reported annually with total follow up of 48 months. Analyses used linear mixed
      models. RESULTS: Among participants with baseline radiographic knee OA the mean
      total magnesium intake was 309.9 mg/day (SD 132.6) for men, and 287.9 mg/day (SD
      118.1) for women, with 68% of men and 44% of women below the estimated average
      requirement. Subjects with lower magnesium intake had worse knee OA pain and
      function scores, throughout the 48 months (P < 0.001). After adjustment for age,
      sex, race, body mass index (BMI), calorie intake, fiber intake, pain medication
      use, physical activity, renal insufficiency, smoking, and alcohol use, lower
      magnesium intake remained associated with worse pain and function outcomes (1.4
      points higher WOMAC and 1.5 points lower KOOS scores for every 50 mg of daily
      magnesium intake, P < 0.05). Fiber intake was an effect modifier (P for
      interaction <0.05). The association between magnesium intake and knee pain and
      function scores was strongest among subjects with low fiber intake. CONCLUSION:
      Lower magnesium intake was associated with worse pain and function in knee OA,
      especially among individuals with low fiber intake.

PMID- 29454595
TI  - Growth hormone promotes synaptogenesis and protects neuroretinal dendrites
      against kainic acid (KA) induced damage.
AB  - There is increasing evidence that suggests a possible role for GH in retinal
      development and synaptogenesis. While our previous studies have focused largely
      on embryonic retinal ganglion cells (RGCs), our current study demonstrates that
      GH has a synaptogenic effect in retinal primary cell cultures, increasing the
      abundance of both pre- (SNAP25) and post- (PSD95) synaptic proteins. In the
      neonatal chick, kainate (KA) treatment was found to damage retinal synapses and
      abrogate GH expression. In response to damage, an increase in Cy3-GH
      internalization into RGCs was observed when administered shortly before or after
      damage. This increase in internalization also correlated with increase in PSD95
      expression, suggesting a neuroprotective effect on the dendritic trees of RGCs
      and the inner plexiform layer (IPL). In addition, we observed the presence of
      PSD95 positive Muller glia, which may suggest GH is having a neuroregenerative
      effect in the kainate-damaged retina. This work puts forth further evidence that
      GH acts as a synaptogenic modulator in the chick retina and opens a new
      possibility for the use of GH in retinal regeneration research.

PMID- 29454596
TI  - Comparatively study on the insulin-regulated glucose homeostasis through brain
      gut peptides in Japanese flounder Paralichthys olivaceus after intraperitoneal
      and oral administration of glucose.
AB  - The present study comparatively analyzed the blood glucose and insulin
      concentration, the temporal and spatial expression of brain-gut peptides and the
      key enzymes of glycolysis and gluconeogenesis in Japanese flounder by
      intraperitoneal injection (IP) and oral administration (OR) of glucose. Samples
      were collected at 0, 1, 3, 5, 7, 9, 12, 24 and 48 h after IP and OR glucose,
      respectively. Results showed that the hyperglycemia lasted for about 10 h and 21
      h in OR and IP group, respectively. The serum insulin concentration significantly
      decreased at 3 h (1.58 +/- 0.21 mIU/L) after IP glucose. However, it
      significantly increased at 3 h (3.37 +/- 0.341 mIU/L) after OR glucose. The gene
      expressions of prosomatostatin, neuropeptide Y, cholecystokinin precursor and
      orexin precursor in the brain showed different profiles between the OR and IP
      group. The OR not IP administration of glucose had significant effects on the
      gene expressions of preprovasoactive intestinal peptide, pituitary adenylate
      cyclase activating polypeptide and gastrin in intestine. In conclusion, brain-gut
      peptides were confirmed in the present study. And the serum insulin and the brain
      gut peptides have different responses between the IP and OR administration of
      glucose. The OR could stimulate the brain-gut peptide expressions, which have
      effects on the insulin secretion and then regulate the blood glucose levels.
      However, in IP group, there is little chance to stimulate brain-gut peptide
      expression to influence the insulin secretion, which leads to a longer
      hyperglycemia.

PMID- 29454597
TI  - CRT-D oversensing storm by contacted electromagnetic interference.

PMID- 29454598
TI  - Use of intravenous vernakalant for atrial fibrillation conversion in the regular
      ward under only bedside monitoring.

PMID- 29454599
TI  - Vascularized Bone Graft to the Lunate Combined With Temporary Scaphocapitate
      Fixation for Treatment of Stage III Kienbock Disease: A Report of the Results, a
      Minimum of 2 Years After Surgery.
AB  - PURPOSE: To report the outcomes of patients with stage III Kienbock disease
      treated by vascularized bone graft (VBG) followed by temporary scaphocapitate
      (SC) fixation, a minimum of 2 years after surgery. METHODS: Twenty-six patients
      (mean age, 35 years) with stage III Kienbock disease (16 with stage IIIA and 10
      with stage IIIB), treated with VBG followed by SC fixation for 4 months, were
      retrospectively followed for at least 2 years (range, 24-121 months; mean, 61.8
      months). The preoperative and postoperative assessments included range of motion
      (ROM) of the wrist, grip strength (GS), wrist pain, the modified Mayo wrist score
      (MMWS), carpal height ratio (CHR), Stahl index (STI), and radioscaphoid angle
      (RSA). The outcomes of each assessment of the stages IIIA and IIIB groups at the
      final examination were compared with those before surgery. RESULTS: In both
      stages IIIA and IIIB groups, GS increased after surgery. Decrease of CHR and STI
      was associated with the increase of RSA in the stage IIIA group after surgery,
      while RSA decreased, although neither CHR nor STI significantly increased in the
      stage IIIB patients. No patient demonstrated deterioration of the wrist pain
      after surgery. Twenty-one of 26 patients had an improved MMWS grade at the final
      follow-up. CONCLUSIONS: Vascularized bone graft combined with SC fixation for 4
      months provided greater GS, pain relief, and functional improvement compared with
      before surgery in both stages IIIA and IIIB groups. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 29454600
TI  - New Methods to Assess Forearm Torque and Lifting Strength: Reliability and
      Validity.
AB  - PURPOSE: To determine the repeatability and validity of new methods designed to
      objectively measure forearm torque and lifting strength in a clinical setting.
      METHODS: Twenty-eight healthy volunteers, 19 women and 9 men, were tested for
      lifting strength and forearm torque with the Kern and Baseline dynamometers. Two
      raters tested each participant on 3 occasions in the standing position. One of
      the raters also examined 15 subjects, 3 times, for forearm torque in the seated
      position and for lifting strength and forearm torque by the Work Simulator II,
      Baltimore Therapeutic Equipment (BTE II). Intraclass correlation coefficients
      (ICC) model 2,1 was used to calculate ICCs for intra- and interrater reliability.
      The same ICC model and Bland-Altman plots were used to analyze the validity and
      agreement between the new test methods and the BTE II equipment and for
      comparison between tests performed in the standing and seated positions. RESULTS:
      Intra- and interrater reliability for forearm torque measurements with both the
      Baseline and the BTE II demonstrated ICCs between 0.88 and 0.96. The comparison
      between the Baseline and the BTE equipment yielded lower ICCs of 0.74 to 0.88 but
      they were still substantial and in good agreement. The ICCs for torques recorded
      in the standing and seated position were 0.89 to 0.96. Lifting strength, measured
      in 3 different positions of forearm rotation, yielded ICC values between 0.84 and
      0.96 for both raters and with both the Kern and the BTE II instruments.
      Similarly, comparisons between the Kern and the BTE II methods showed ICC values
      between 0.91 and 0.95. CONCLUSIONS: Both the Baseline and the Kern dynamometers
      demonstrated excellent intra- and interrater repeatability. Except for forearm
      torque test in direction of pronation, which had a slightly lower ICC of 0.74,
      our new methods were valid when the BTE II was used as the reference standard.
      Assessments in the standing or seated position for torque measurements made
      little difference. Thus, we found the quality of measurements performed with our
      new methods sufficient for future studies of forearm torque and lifting strength.
      CLINICAL RELEVANCE: Simple, yet reliable, methods to quantify torque and lifting
      strength in a clinical setting have the potential to improve evaluations of wrist
      and forearm disorders as well as their treatments.

PMID- 29454602
TI  - ?

PMID- 29454601
TI  - Cross-linked polyethylene does not reduce wear in total knee arthroplasty.
AB  - AIM: To compare two different types of inserts: Ultra-high molecular weight
      polyethylene (UHMWPE) and cross-linked polyethylene with a quantitative and
      qualitative study of polyethylene wear particles in synovial fluid 3 years after
      total knee arthroplasty. MATERIAL AND METHODS: A prospective, randomized,
      controlled cohort study with blinded evaluation was carried out on 25 patients
      undergoing staged bilateral total knee replacement, 6 months apart. Knee
      arthrocentesis was performed on 12 patients 3 years after surgery, and the
      polyethylene particles were analyzed. RESULTS: No significant differences were
      found in the number of particles generated by the two different types of inserts
      at 3 years from total knee arthroplasty (3,000*: x- cross-linked=849.7; x-
      UHMWPE=796.9; P=.63; 20,000*: x- cross-linked=66.3; x- UHMWPE=73.1; P=.76).
      Likewise, no differences in the probability of finding elongated (chi2=0.19;
      P=.66) or rounded (chi2=1.44; P=.23) particles in both types of inserts were
      observed. However, the probability of finding fibrillar particles is 3.08 times
      greater in UHMWPE. CONCLUSIONS: Cross-linked polyethylene does not significantly
      reduce the generation of polyethylene particles in patients with total knee
      arthroplasty, 3 years after the surgical procedure.

PMID- 29454603
TI  - ?

PMID- 29454605
TI  - Knowledge of sudden unexpected death in epilepsy (SUDEP) among 372 patients
      attending a German tertiary epilepsy center.
AB  - BACKGROUND: There is evidence that the sudden unexpected death in epilepsy
      (SUDEP) risk can be reduced by good seizure control, nocturnal supervision, and
      by early cardiopulmonary resuscitation if cardiorespiratory arrest occurs in the
      aftermaths of generalized tonic-clonic seizures (GTCS). These measures, however,
      may critically depend on the knowledge of patients and relatives on SUDEP. Here,
      we assessed the basic knowledge on SUDEP of people with epilepsy at a tertiary
      epilepsy center in Germany. METHODS: Adult patients with epilepsy and relatives
      or caregivers of patients with epilepsy aged 16years or older attending our
      outpatient clinic from January to March 2014 were given the opportunity to
      participate in a (assisted or unassisted) written survey. In the anonymized
      questionnaire, people were asked if they had already heard about SUDEP, by what
      means and if they wish to learn (more) about SUDEP. Furthermore, age, sex,
      epilepsy duration, highest degree of education, number of GTCS during the last
      year, and estimation of subjective impairment by their disease were assessed.
      Statistics were done using mixed linear or logistic regression models. RESULTS: A
      total of 372 patients' questionnaires were included in this survey. More than 87%
      of the participants had never heard of SUDEP before. Whereas about 50% of the
      participants wanted to learn more about SUDEP, about 40% did not. Only the age at
      survey was significantly associated with both being informed and the desire of
      learning more about SUDEP: Younger patients had more often heard (p=0.022) and
      wanted to know more about SUDEP (p=0.020). Thirty-nine patients were considered
      at high risk for SUDEP. Of these, only 6 patients (15%) knew about SUDEP prior to
      this survey, but 18 patients (46%) wanted to learn more about this fatal
      complication. CONCLUSION: Our data suggest that the level of information on SUDEP
      among people with epilepsy is poor in Germany regardless of sex, school
      education, or epilepsy severity. Additionally, a considerable proportion of
      people with epilepsy seems to prefer not getting detailed information on SUDEP.
      More efforts are required to understand the potential barriers of the education
      of patients and relatives on sudden death with the ultimate goal of decreasing
      the risk of SUDEP.

PMID- 29454604
TI  - Cytotoxic and inflammatory effects of alendronate and zolendronate on human
      osteoblasts, gingival fibroblasts and osteosarcoma cells.
AB  - OBJECTIVE: The aim of this paper was to assess the effects of zoledronate (ZOL)
      and alendronate (FOS) on apoptotic behavior and gene expression of pro- and
      inflammatory cytokines of three cell types (human osteoblasts, human gingival
      fibroblasts and human osteogenic sarcoma cell lines) during a period of 4 weeks.
      MATERIAL AND METHODS: Cell viability and proliferation was assessed via cell
      proliferation test (MTT), fluorescence diacetate analysis (FDA). Expression of
      inflammatory cytokines was investigated by using polymerase chain reaction.
      RESULTS: The proliferation and cell vitality of osteoblasts and fibroblasts were
      negatively affected in a dose dependent manner under ZOL and FOS administration.
      Osteosarcoma cells showed an increase in proliferation under lower doses of BP.
      ZOL had a significantly higher cytotoxic effect compared with FOS on osteoblasts
      and fibroblasts. ZOL increased the production of IL-6 in all cell types, whereas
      FOS only in osteosarcoma cell, which happened in dose dependent manner.
      Bisphosphonates could result in increase of IL-1beta expression of fibroblasts.
      An increase of IL-12 was observed at higher doses of ZOL administration among
      osteoblasts and FOS administration in osteosarcoma cells. CONCLUSION: ZOL and FOS
      could encourage cytotoxic and inflammatory reactions.

PMID- 29454606
TI  - Psychosocial outcome in epilepsy after extratemporal surgery.
AB  - OBJECTIVE: Only limited data exist on psychosocial long-term outcome after
      epilepsy surgery in patients with extratemporal epilepsy. The aim of this study
      was to investigate psychosocial outcome after extratemporal epilepsy surgery and
      to assess factors predicting favorable outcome. METHOD: Sixty-five out of 104
      eligible patients who had undergone extratemporal epilepsy surgery at our
      epilepsy center between 1990 and 2015 (mean age: 42.2. years; 75% of the
      resections in the frontal lobe) completed a questionnaire asking about seizure
      status, employment status, marital and living situation, driving status,
      depressive symptoms, and quality of life (QOL). Follow-up was on average 9.2years
      after surgery (range: 1-26years). RESULTS: Thirty-eight (58%) patients were free
      of disabling seizures (Engel class I), and 28 (43%) have not experienced any
      seizures after surgery (Engel class IA). Employment rate in the primary labor
      market remained at 45%, but more patients lost employment (14%) than gained
      employment (8%). Postoperative employment was predicted by preoperative
      employment (p=.007), seizure freedom (p=.025), older age at seizure onset
      (p=.018), younger age at follow-up (p=.035), and female gender (p=.048). Seizure
      free patients were more likely to be driving; have a partner, particularly in
      males; and have lower depressive scores. Quality of life at follow-up was best
      predicted by employment (p=.012), partnership (p=.025), and seizure freedom
      (p=.025). In contrast, recurrence of seizures and early seizure onset were
      associated with poor psychosocial outcome, particularly in men. CONCLUSION: The
      study provides support that extratemporal surgery can lead to improved QOL and
      favorable psychosocial outcome. Seizure freedom is important but not the only
      determinant of good psychosocial outcome.

PMID- 29454607
TI  - Italian Wikipedia and epilepsy: An infodemiological study of online information
      seeking behavior.
AB  - Wikipedia is the most commonly accessed source of health information by both
      healthcare professionals and the lay public worldwide. We aimed to evaluate
      information-seeking behavior of Internet users searching the Italian Wikipedia
      for articles related to epilepsy and its treatment. Using Pageviews Analysis, we
      assessed the total and mean monthly views of articles from the Italian Wikipedia
      devoted to epilepsy, epileptic syndromes, seizure type, and antiepileptic drugs
      (AEDs) from January 1, 2015 to October 31, 2017. We compared the views of the
      article on epilepsy with those of articles focusing on Alzheimer's disease,
      migraine, multiple sclerosis, syncope, and stroke and adjusted all results for
      crude disease prevalence. With the only exception of the article on multiple
      sclerosis, the adjusted views for the Italian Wikipedia article on epilepsy were
      higher than those for the other neurological disorders. The most viewed articles
      on seizure type were devoted to tonic-clonic seizure, typical absence seizure,
      tonic convulsive seizures, and clonic convulsive seizures. The most frequently
      accessed articles on epilepsy syndromes were about temporal lobe epilepsy and
      Lennox-Gastaut syndrome. The most frequently viewed articles on AEDs were devoted
      to valproic acid, carbamazepine, and levetiracetam. Wikipedia searches seem to
      mirror patients' fears and worries about epilepsy more than its actual
      epidemiology. The ultimate reasons for searching online remain unknown.
      Epileptologists and epilepsy scientific societies should make greater efforts to
      work jointly with Wikipedia to convey more accurate and up-to-date information
      about epilepsy.

PMID- 29454608
TI  - miRNA-185 serves as a prognostic factor and suppresses migration and invasion
      through Wnt1 in colon cancer.
AB  - Colon cancer is one of the deadliest cancers worldwide; abnormal microRNA
      expression is common during colon cancer development. The aim of the present
      study was to elucidate the role played by miR-185 in this context. We used
      quantitative real-time PCR (qRT-PCR) to measure miR-185 expression levels in
      colon cancer cell lines. The effects of miR-185 on colon cancer cell
      proliferation and invasion were assessed using the MTT, colony-forming, wound
      healing, and transwell assays. A luciferase activity assay was used to confirm
      the target of miR-185. Our data showed that miR-185 was significantly down
      regulated in colon cancer cells and colonic cancer tissues compared with NCM460
      normal colonic epithelial cells and adjacent normal tissues. A functional
      analysis revealed that ectopic expression of miR-185 significantly inhibited
      colon cancer cell proliferation, colony formation, migration, and invasion. In
      addition, western blot, qRT-PCR, and luciferase assays confirmed in colon cancer
      cells that Wnt1 was a downstream target of miR-185, in turn suppressing beta
      catenin-mediated signaling. In conclusion, we found that miR-185 inhibits colon
      cancer cell proliferation and invasion by targeting Wnt1, and that it serves as a
      tumor suppressor, indicating that the modulation of miR-185 levels may
      potentially be therapeutic in colon cancer patients.

PMID- 29454609
TI  - Deubiquitinase inhibitor b-AP15 activates endoplasmic reticulum (ER) stress and
      inhibits Wnt/Notch1 signaling pathway leading to the reduction of cell survival
      in hepatocellular carcinoma cells.
AB  - b-AP15, a potent and selective inhibitor of the ubiquitin-specific peptidase 14
      (USP14), displays in vitro and in vivo antitumor abilities on some types of
      cancer cells. However, the mechanism underlying its action is not well
      elucidated. The purposes of the present study are to observe the potential
      impacts of b-AP15 on cell survival of hepatocellular carcinoma cells and to
      investigate whether and how this compound inhibits some survival-promoting
      signaling pathways. We found that b-AP15 significantly decreased cell viability
      and increased cell apoptosis in a dose-dependent manner in hepatocellular
      carcinoma cells, along with the perturbation of cell cycle and the decreased
      expressions of cell cycle-related proteins. We also demonstrated that the
      endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) were
      enhanced by b-AP15 supplementation. The inhibition of ER stress/UPR only partly
      attenuated the cytotoxicity of b-AP15 on hepatocellular carcinoma cells. In
      addition, b-AP15 treatment inhibited Wnt/beta-catenin and Notch1 signaling
      pathways, and suppressed phosphorylation of STAT3, Akt, and Erk1/2, which were
      not restored by the inhibition of ER stress/UPR. Furthermore, the expression
      levels of signaling molecules in Notch1 were reduced by specific inhibitor of
      Wnt/beta-catenin pathway. Notably, either Wnt or Notch1 signaling inhibitor
      mitigated phosphorylation of STAT3, Akt, and Erk1/2, and mimicked the
      cytotoxicity of b-AP15 on hepatocellular carcinoma cells. These results clearly
      indicate that b-AP15 induced cytotoxic response to hepatocellular carcinoma cells
      by augmenting ER stress/UPR and inhibiting Wnt/Notch1 signaling pathways. This
      new finding provides a novel mechanism by which b-AP15 produces its antitumor
      therapeutic effects.

PMID- 29454610
TI  - Direct and indirect effects of ephedrine on heart rate and blood pressure in
      vehicle-treated and sympathectomised male rats.
AB  - We have investigated the cardiac and pressor responses to (+/-)-ephedrine and (-)
      ephedrine in pentobarbitone anaesthetized male wistar rats. The tachycardiac
      responses to (+/-)- and (-)-ephedrine were similar, but pressor responses to (-)
      ephedrine (10 mg/kg) were significantly greater than those to (+/-)-ephedrine,
      and for both, the pressor response was followed by a small depressor response.
      Sympathectomy did not affect pressor responses, but significantly increased the
      later depressor response to both compounds. Sympathectomy did not affect
      tachycardiac or depressor responses to the beta-adrenoceptor agonist
      isoprenaline, but significantly reduced the tachycardia to (+/-)-ephedrine. (+/-)
      Ephedrine contracted vas deferens from vehicle treatment animals, but in vas
      deferens from sympathectomised rats, (+/-)-ephedrine produced almost no tonic
      contraction (alpha1A-adrenoceptor mediated), but the phasic contraction was
      unaffected (alpha1D-adrenoceptor mediated). It is concluded, firstly, that (-)
      ephedrine is more potent than the racemate mixture at producing pressor
      responses. Secondly, since the depressor response to isoprenaline was unaffected,
      sympathectomy presumably reduced a pressor component to the response to (+/-)-
      and (-)-ephedrine. Hence, a component of the pressor response to both (+/-)- and
      (-)-ephedrine is indirect and may involve actions at alpha1A-adrenoceptors, at
      which ephedrine does not have marked direct actions.

PMID- 29454611
TI  - Taste receptor plasticity in relation to feeding history in two congeneric
      species of Papilionidae (Lepidoptera).
AB  - In the peripheral taste system of insects, the responsiveness of gustatory
      receptor neurons (GRNs) depends on several factors, such as larval instar,
      feeding history, physiological state and time of day. To study the role of the
      feeding history, the spike activity of the maxillary taste chemosensilla in the
      larvae of two related species of Lepidoptera (Papilio machaon L. and Papilio
      hospiton Gene) raised on different host plants, was recorded with
      electrophysiological techniques after stimulation with simple stimuli (sugars,
      bitters and inorganic salt) and host plant saps, with the aim of cross-comparing
      their response patterns and evaluating any effects of different feeding
      histories. For this purpose the larvae were raised each on their preferential
      host plant and, in addition, P. machaon larvae was also raised on Ferula
      communis, the host plant preferred by P. hospiton. The GRN spike activity of the
      lateral and medial sensilla of each test group was measured in response to simple
      and complex stimuli. The taste discrimination capabilities and modalities of the
      two species were measured and cross-compared with the aim of studying convergence
      and/or divergence linked to the insect feeding history. The results show that: a)
      the GRN responsiveness of both sensilla in P. machaon raised on Fe. communis
      differs significantly from that of P. machaon on Foeniculum vulgare, but is not
      different from P. hospiton on Fe. communis; b) P. machaon larvae raised on Fe.
      communis exhibit response spectra somewhat intermediate between those of P.
      machaon on fennel and of P. hospiton on Fe. communis, the latter two exhibiting a
      wider difference from each other; c) the pattern of GRNs activity generated by
      each plant sap in both sensilla of P. machaon raised on Fe. communis is different
      from that generated when raised on Fo. vulgare, while no difference is observed
      with P. hospiton. The data support the hypothesis that diet-related factors may
      influence peripheral chemosensitivity in lepidopterous larvae.

PMID- 29454612
TI  - Ecdysteroidogenesis and development in Heliothis virescens (Lepidoptera:
      Noctuidae): Focus on PTTH-stimulated pathways.
AB  - Post-embryonic development and molting in insects are regulated by endocrine
      changes, including prothoracicotropic hormone (PTTH)-stimulated ecdysone
      secretion by the prothoracic glands (PGs). In Lepidoptera, two pathways are
      potentially involved in PTTH-stimulated ecdysteroidogenesis, mitogen-activated
      protein kinase (MAPK) and phosphoinositide 3-kinase/protein kinase B/target of
      rapamycin (PI3K/Akt/TOR). We investigated the potential roles of both these
      pathways in Heliothis virescens ecdysteroidogenesis. We identified putative
      proteins belonging to MAPK and PI3K/Akt/TOR signaling cascades, using
      transcriptomic analyses of PGs from last (fifth) instar larvae. Using western
      blots, we measured the phosphorylation of 4E-BP and S6K proteins, the main
      targets of TOR, following the in vitro exposure of PGs to brain extract
      containing PTTH (hereafter referred to as PTTH) and/or the inhibitors of MAPK
      (U0126), PI3K (LY294002) or TOR (rapamycin). Next, we measured ecdysone
      production, under the same experimental conditions, by enzyme immunoassay (EIA).
      We found that in Heliothis virescens last instar larvae, both pathways modulated
      PTTH-stimulated ecdysteroidogenesis. Finally, we analyzed the post-embryonic
      development of third and fourth instar larvae fed on diet supplemented with
      rapamycin, in order to better understand the role of the TOR pathway in larval
      growth. When rapamycin was added to the diet of larvae, the onset of molting was
      delayed, the growth rate was reduced and abnormally small larvae/pupae with high
      mortality rates resulted. In larvae fed on diet supplemented with rapamycin, the
      growth of PGs was suppressed, and ecdysone production and secretion were
      inhibited. Overall, the in vivo and in vitro results demonstrated that, similarly
      to Bombyx mori, MAPK and PI3K/Akt/TOR pathways are involved in PTTH signaling
      stimulated ecdysteroidogenesis, and indicated the important role of TOR protein
      in H. virescens systemic growth.

PMID- 29454613
TI  - Isoquercetin attenuates oxidative stress and neuronal apoptosis after
      ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF
      kappaB pathway.
AB  - Isoquercetin (Iso) has been found to have neuroprotective effects against
      cerebral ischemic stroke. However, the exact molecular mechanism underlying its
      neuroprotective ability remains unclear. In this study, we aimed to evaluate the
      neuroprotective effects of Iso in primary culture of rat hippocampal neurons
      exposed to oxygen and glucose deprivation and reperfusion (OGD/R) injury and in
      rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R)
      injury. We found that rats treated with Iso exhibited a lower degree of infarct
      volume, and brain water content than the vehicle-treated rats. Treatment with Iso
      also improved the neurological deficits in MCAO/R rats as shown by the decreased
      modified neurological severity score. Iso treatment decreased the reactive oxygen
      species (ROS) and malondialdehyde (MDA) production, and increased the activity of
      superoxide dismutase (SOD) and catalase (CAT) in brains of MCAO/R rats and
      primary culture of rat hippocampal neurons exposed to OGD/R. Iso treatment
      prevents I/R-induced neuronal apoptosis in vivo and in vitro as indicated by
      increased cell viability and decreased number of TUNEL-positive cells,
      accompanying with downregulation of cleaved caspase-3 protein and upregulation of
      Bcl-2 protein. Moreover, Nrf2 knockdown weakened the anti-apoptotic and anti
      oxidant activities of Iso in primary culture of rat hippocampal neurons exposed
      to OGD/R. Interestingly, we found that Iso could induce Nrf2 translocation from
      cytoplasm to nucleus in primary culture of rat hippocampal neurons exposed to
      OGD/R. Iso activated the NOX4/ROS/NF-kappaB signaling pathway in in vivo and in
      vitro cerebral I/R injury models. Nrf2 knockdown blocked the inhibitory effect of
      Iso on protein expression of NOX4, p-IkappaBalpha and p-p65 in primary culture of
      rat hippocampal neurons exposed to OGD/R. All the data suggested that Iso
      protected against oxidative stress and neuronal apoptosis in in vivo and in vitro
      cerebral I/R injury models via Nrf2-mediated inhibition of the NOX4/ROS/NF-kappaB
      signaling pathway. Our findings suggested that Iso could be a potential agent for
      I/R brain injury.

PMID- 29454614
TI  - Selenium deficiency aggravates T-2 toxin-induced injury of primary neonatal rat
      cardiomyocytes through ER stress.
AB  - Keshan disease is a potentially fatal cardiomyopathy in humans. Selenium
      deficiency, T-2 toxin, and myocarditis virus are thought to be the major factors
      contributing to Keshan disease. But the relationship among these three factors is
      poorly described. This study aims to explore whether selenium deficiency
      aggravates T-2 toxin-induced cardiomyocyte injury and its underlying mechanism.
      Cardiomyocytes were isolated from neonatal rat and cultured at the physiological
      (2.0 MUM) or lower concentrations of selenium with different concentrations of T
      2 toxin. Our results showed that selenium deficiencies aggravated T-2 toxin
      induced cardiomyocyte injury in a concentration-dependent manner as demonstrated
      by MTT bioassay, LDH activity, reactive oxygen species levels and caspase 3
      protein expressions. T-2 toxin treatment significantly increased mRNA expressions
      for stress proteins GRP78 and CHOP in cardiomyocytes compared with the control.
      Selenium deficiencies further promoted GRP78, CHOP and p-eIF2alpha expressions.
      Knockdown of CHOP by the specific small interfering RNA eliminated the effect of
      selenium deficiencies on T-2 toxin-induced injury. It could be concluded that
      selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury through
      initiating more aggressive endoplasmic reticulum stress.

PMID- 29454615
TI  - Synthesis and biological investigation of new carbonic anhydrase IX (CAIX)
      inhibitors.
AB  - In this report, we describe the synthesis, characterization, in vitro anticancer
      activity and Carbonic anhydrase IX (CAIX) inhibition of new sulfamate conjugates
      of Betulin and Betulinic acid (BA). The betulinyl sulfamates were subjected to
      inhibit carbonic anhydrases (CA), e.g. CAIX, an attractive target for tumor
      selective therapy strategies in cancer cells. Data on combined in vitro antitumor
      activity with CAIX inhibition are very rare. The betulinyl sulfamates were tested
      against five tumor cell lines and normal human skin fibroblasts. The mode of cell
      death on MCF7 breast cancer cells induced by the most active compounds CAI1, CAI3
      and CAI6 was investigated by Fluorescence Activated Cell Sorting (FACS)
      experiments. The compounds showed inhibitory activity towards CAIX, which was
      determined via in vitro enz-yme assay. Our preliminary investigations revealed
      that all compounds showed potent anticancer properties with IC50 values below 20
      MUM against all tumor cells. Interestingly, among the panel of sulfamate
      conjugates, CAI3 found to be highly cytotoxic (average IC50 = 5-10 MUM) and
      possess high inhibitory activity (Ki = 1.25 nM) towards CAIX. Our results suggest
      that betulinyl sulfamates seem to be attractive substances, due to their
      possibility of targeted drug delivery they deserve to be proceeded for further
      pre-clinical (kinetic studies) and in vivo investigations.

PMID- 29454616
TI  - Zoledronate modulates intracellular vesicle trafficking in mast cells via
      disturbing the interaction of myosinVa/Rab3a and sytaxin4/VAMP7.
AB  - Nitrogen-containing bisphosphonates (NBPs) have been widely used as bone anti
      resorptive drugs for the treatment of osteoclast-dependent bone disorders.
      Zoledronate is currently the most potent NBP, and has potential as an inhibitor
      of farnesyl pyrophosphate synthase. The present study was undertaken to elucidate
      the possible effects of zoledronate on FcepsilonRI-dependent mast cell activity
      in vitro, which is essential for in maintaining homeostasis of the
      gastrointestinal mucosa. Treatment with zoledronate significantly diminished
      exocytosis of mast cells, which was reflected by a decrease of FcepsilonRI
      dependent histamine release compared to that in vehicle-treated mast cells. Our
      single-vesicle monitoring and biochemical results suggested that zoledronate
      modulates intracellular formation of the myosinVa/Rab3a complex and
      syntaxin4/VAMP7 complex, which are critical in vesicle motility, and therefore
      disturbs exocytosis via suppression of the velocity of intracellular vesicles and
      inhibition of membrane fusion. Our findings imply that oral administration of
      zoledronate could modulate mucosal immune function by blocking mast cell
      function, and this risk should be of concern in the clinical usage of NBPs.

PMID- 29454617
TI  - Antihypertensive potential of linalool and linalool complexed with beta
      cyclodextrin: Effects of subchronic treatment on blood pressure and vascular
      reactivity.
AB  - Linalool (LIN) is a monoterpene alcohol present in some aromatic medicinal plants
      with biological activities that can impact cardiovascular diseases. This chemical
      class is highly volatile and beta-cyclodextrin (beta-CD) has been employed to
      improve the pharmacological properties of monoterpenes. Thus, the aim of this
      study was to evaluate the cardiovascular effects of LIN free focusing on the
      antihypertensive properties of this monoterpene and to study whether LIN,
      complexed in beta-cyclodextrin (LIN-betaCD) is able to improve the
      pharmacological activity of LIN. Spontaneously hypertensive rats (SHR) were
      randomly divided into 5 groups, each treated daily for 21 days, in the following
      manner: group 1 (vehicle solution); group 2 (captopril; 30 mg/kg/day); group 3
      (LIN; 100 mg/kg/day); group 4 (LIN; 50 mg/kg/day) and group 5 (LIN/beta-CD; 50
      mg/kg/day). Daily body weight measurements were conducted and mean arterial
      pressure and heart rate were measured every 5 days. The mesenteric artery from
      treated animals was tested for phenylephrine and sodium nitroprusside (SNP)
      sensitivity. The SHR treated with vehicle demonstrated progressive increase in
      mean arterial pressure and captopril, a positive control, induced a significant
      decrease. After 21 days of treatment, the blood pressure of the SHR treated by (
      )-LIN (100 mg/kg) was significantly reduced. In addition, various important
      cardiovascular parameters improved, including: the treatment with LIN prevented
      the development of cardiac hypertrophy, increased levels of the anti-inflammatory
      cytokine (IL-10), increased vasodilator responsiveness and reduced sensitivity to
      the sympathetic agonist. Furthermore, the inclusion complex containing LIN in
      beta-CD produced a higher antihypertensive profile when compared with uncomplexed
      form. Taking together, our results suggested that LIN shown a potential
      antihypertensive effect and beta-CD may be an important tool to improve the
      cardiovascular activity of LIN and other water-insoluble compounds.

PMID- 29454618
TI  - Natural small molecule bigelovin suppresses orthotopic colorectal tumor growth
      and inhibits colorectal cancer metastasis via IL6/STAT3 pathway.
AB  - Bigelovin, a sesquiterpene lactone, has been demonstrated to induce apoptosis,
      inhibit inflammation and angiogenesis in vitro, but its potential anti-metastatic
      activity remains unclear. In the present study, two colon cancer mouse models,
      orthotopic tumor allografts and experimental metastatic models were utilized to
      investigate the progression and metastatic spread of colorectal cancer after
      bigelovin treatments. Results showed that bigelovin (intravenous injection; 0.3-3
      mg/kg) significantly suppressed tumor growth and inhibited liver/lung metastasis
      with modulation of tumor microenvironment (e.g. increased populations of T
      lymphocytes and macrophages) in orthotopic colon tumor allograft-bearing mice.
      Furthermore, the inhibitory activities were also validated in the experimental
      human colon cancer metastatic mouse model. The underlying mechanisms involved in
      the anti-metastatic effects of bigelovin were then revealed in murine colon tumor
      cells colon 26-M01 and human colon cancer cells HCT116. Results showed that
      bigelovin induced cytotoxicity, inhibition of cell proliferation, motility and
      migration in both cell lines, which were through interfering IL6/STAT3 and
      cofilin pathways. Alternations of the key molecules including Rock, FAK, RhoA,
      Rac1/2/3 and N-cadherin, which were detected in bigelovin-treated cancer cells,
      were also observed in the tumor allografts of bigelovin-treated mice. These
      findings strongly indicated that bigelovin has potential to be developed as anti
      tumor and anti-metastatic agent for colorectal cancer.

PMID- 29454619
TI  - Delineation of the functional properties and the mechanism of action of AA29504,
      an allosteric agonist and positive allosteric modulator of GABAA receptors.
AB  - The retigabine analog 2-amino-4-[(2,4,6-trimethylbenzylamino)-phenyl]-carbamic
      acid ethyl ester (AA29504) is a positive allosteric modulator (PAM) of gamma
      aminobutyric acidA receptors (GABAARs), and the modulator has been used in ex
      vivo/in vivo studies to probe the physiological roles of native delta-containing
      GABAARs. In this study, the functional properties and mode of action of AA29504
      were investigated at human GABAARs expressed in Xenopus oocytes by two-electrode
      voltage clamp electrophysiology. AA29504 was found to be an allosteric GABAAR
      agonist displaying low intrinsic activities at 3-30 MUM. AA29504 was essentially
      equipotent as a PAM at the 13 GABAAR subtypes tested (EC50: 0.45-5.2 MUM),
      however GABA EC5-evoked currents through alphabetadelta subtypes were modulated
      to substantially higher levels than those through alphabetagamma2S subtypes
      (relative to GABA Imax). While the delta/gamma2S-difference clearly was key for
      this differential GABA efficacy modulation, studies of the AA29504-mediated
      modulation of different alpha4,5,6-containing alphabeta, alphabetagamma2S and
      alphabetadelta GABAARs revealed the alpha-subunit identity to be another
      important determinant. Based on its functional properties at numerous mutant
      GABAARs and on in silico analysis of its low-energy conformations, AA29504 is
      proposed to act through an allosteric site in the transmembrane beta(+)/alpha(-)
      interface in the GABAAR also targeted by etomidate and several other modulators.
      In contrast to these modulators, however, AA29504 did not display substantial
      beta2/beta3-over-beta1 GABAAR preference, which challenges the notion of ligands
      targeting this site always possessing this subtype-selectivity profile. Hence,
      the detailed pharmacological profiling of AA29504 both highlights the complexity
      of allosteric GABAAR modulation and provides valuable information about this
      modulator as a pharmacological tool.

PMID- 29454621
TI  - The G protein-coupled receptors deorphanization landscape.
AB  - G protein-coupled receptors (GPCRs) are usually highlighted as being both the
      largest family of membrane proteins and the most productive source of drug
      targets. However, most of the GPCRs are understudied and hence cannot be used
      immediately for innovative therapeutic strategies. Besides, there are still
      around 100 orphan receptors, with no described endogenous ligand and no clearly
      defined function. The race to discover new ligands for these elusive receptors
      seems to be less intense than before. Here, we present an update of the various
      strategies employed to assign a function to these receptors and to discover new
      ligands. We focus on the recent advances in the identification of endogenous
      ligands with a detailed description of newly deorphanized receptors. Replication
      being a key parameter in these endeavors, we also discuss the latest
      controversies about problematic ligand-receptor pairings. In this context, we
      propose several recommendations in order to strengthen the reporting of new
      ligand-receptor pairs.

PMID- 29454622
TI  - Development of Adjuvanted Solid Fat Nanoemulsions for Pulmonary Hepatitis B
      Vaccination.
AB  - Pulmonary vaccination is one of the most promising routes for immunization owing
      to its noninvasive nature and induction of strong mucosal immunity and systemic
      response. In the present study, recombinant hepatitis B surface antigen loaded
      solid fat nanoemulsions (SFNs) as carrier system and monophosphoryl lipid A as an
      adjuvant-carrier system was prepared and evaluated as multiadjuvanted vaccine
      system for deep pulmonary vaccination. Deposition and clearance from the deep
      lung of rats were determined by gamma scintigraphy. Biodistribution of SFNs was
      determined by the live animal imaging system. SFNs dispersion showed slower
      clearance as compared with sodium pertechnetate control solution (***p <0.001)
      from the pulmonary region due to the virtue of particulate and hydrophobic nature
      of formulations. Humoral (sIgA and IgG) and cellular (IL-2 and IF-gamma) immune
      responses were found to be significant (***p <0.001) when compared with naive
      antigen (recombinant surface antigen without any excipient) solution. Data
      indicate that deep pulmonary immunization offers a stronger immune response with
      balanced humoral, mucosal, and cellular immunization, which further needs to be
      tested in higher animals to support this hypothesis for clinical translation of
      this so far neglected yet potential target tissue for immunization.

PMID- 29454620
TI  - Extracellular loops 2 and 3 of the calcitonin receptor selectively modify agonist
      binding and efficacy.
AB  - Class B peptide hormone GPCRs are targets for the treatment of major chronic
      disease. Peptide ligands of these receptors display biased agonism and this may
      provide future therapeutic advantage. Recent active structures of the calcitonin
      (CT) and glucagon-like peptide-1 (GLP-1) receptors reveal distinct engagement of
      peptides with extracellular loops (ECLs) 2 and 3, and mutagenesis of the GLP-1R
      has implicated these loops in dynamics of receptor activation. In the current
      study, we have mutated ECLs 2 and 3 of the human CT receptor (CTR), to
      interrogate receptor expression, peptide affinity and efficacy. Integration of
      these data with insights from the CTR and GLP-1R active structures, revealed
      marked diversity in mechanisms of peptide engagement and receptor activation
      between the CTR and GLP-1R. While the CTR ECL2 played a key role in
      conformational propagation linked to Gs/cAMP signalling this was mechanistically
      distinct from that of GLP-1R ECL2. Moreover, ECL3 was a hotspot for distinct
      ligand- and pathway-specific effects, and this has implications for the future
      design of biased agonists of class B GPCRs.

PMID- 29454623
TI  - Antisolvent Recrystallization Strategy to Screen Appropriate Carriers to
      Stabilize Filgotinib Amorphous Solid Dispersions.
AB  - Drugs in amorphous solid dispersions (ASDs) are highly dispersed in hydrophilic
      polymeric carriers, which also help to restrain recrystallization and stabilize
      the ASDs. In this study, microscopic observation after antisolvent
      recrystallization was developed as a rapid screening method to select appropriate
      polymers for the initial design filgotinib (FTN) ASDs. Using solvent evaporation,
      FTN ASDs with the polymers were prepared, and accelerated experimentation
      validated this screening method. Fourier-transform infrared spectroscopy, Raman
      scattering, and nuclear magnetic resonance revealed hydrogen-bonding formation in
      the drug-polymer binary system, which was critical for ASDs stabilization. A
      Flory-Huggins interaction parameter and water sorption isotherms were applied to
      evaluate the strength of the interaction between FTN and the polymers. The
      dissolution rate was also significantly improved by ASDs formulation, and the
      presence of the polymers exerted solubilization effects. These results suggested
      the efficacy of this screening method as a preliminary tool for polymer selection
      in ASDs design.

PMID- 29454624
TI  - The Synergetic Effects of Nonpolar and Polar Protic Solvents on the Properties of
      Felodipine and Soluplus in Solutions, Casting Films, and Spray-Dried Solid
      Dispersions.
AB  - The aim was to explore the effects of nonpolar and polar protic solvents composed
      of dichloromethane (DCM) and ethanol (EtOH) on the properties of felodipine
      (FLDP) and Soluplus in solutions, casting films, and spray-dried drug-rich or
      polymer-rich solid dispersions (SDs). Measurement of intrinsic viscosity and
      solubility indicated that FLDP and Soluplus were miscible. EtOH-DCM ranging from
      20:80 to 50:50 induced the strongest molecular interactions for FLDP-Soluplus
      solvents systems. Accordingly, the casting films and spray-dried powders of FLDP
      and Soluplus were prepared using pure EtOH or DCM and their mixtures as solvents.
      Polarized light microscopy, differential scanning calorimetry, Fourier transform
      infrared spectroscopy, in vitro dissolution tests, and stability have been
      conducted to characterize these films or spray-dried powders. EtOH-DCM (50:50)
      showed deltaH 2-3 MPa1/2 higher than FLDP and Soluplus. It exhibited stronger
      inhibitory effects on phase separation and recrystallization of amorphous FLDP
      than pure DCM or EtOH in the drug-rich casting films, spray drying process, and
      spray-dried SDs exposure to 40 degrees C/RH75% for 1 month. Higher ratio of
      Soluplus may offset the effects of solvents on the dissolution and stability of
      polymer-rich SDs. In conclusion, combination of nonpolar and polar protic
      solvents is of high potential for spray drying to optimize drug-rich SDs.

PMID- 29454625
TI  - Intensified nitrogen and phosphorus removal by embedding electrolysis in an
      anaerobic-anoxic-oxic reactor treating low carbon/nitrogen wastewater.
AB  - A modified anaerobic-anoxic-oxic (AAO) reactor embedding electrolysis was
      constructed for treatment of low carbon/nitrogen (C/N) wastewater. The effect of
      different current conditions on the performance of reactor was investigated in
      this study. When the current ranged from 0 mA to 200 mA, the removal efficiency
      of total nitrogen (TN) increased from 61.25% (0 mA) to 75.60% (200 mA), and that
      of total phosphorus (TP) increased from 72.24% (0 mA) to 93.93% (200 mA). In
      addition, the removal efficiencies of chemical oxygen demand (COD) and NH4+-N
      were not affected. The results indicated that AAO reactor coupling electrolysis
      was an effective way to strengthen the removal of nitrogen and phosphorus for
      treatment of low C/N wastewater.

PMID- 29454626
TI  - Effect of adding low-concentration of rhamnolipid on reactor performances and
      microbial community evolution in MBBRs for low C/N ratio and antibiotic
      wastewater treatment.
AB  - This study aims to explore the potential of low-concentration of rhamnolipid in
      efficient treatment of wastewater with poor biodegradability. Six lab-scale
      moving bed biofilm reactors (MBBRs) were applied to investigate the effect of
      rhamnolipid concentration (0, 20, 50 mg/L) on pollutants removal, biomass
      accumulation, microbial morphology and community evolution in synthetic low C/N
      ratio (3:1) and antibiotic (50 MUg/L tetracycline) wastewater. 20 mg/L
      rhamnolipid treated groups exhibited significant increase (p < 0.05) of chemical
      oxygen demand (COD) removal and volatile solid (VS) content in both synthetic
      wastewater. Hydrogenophaga and Aeromonas were dominant in all reactors in which
      Aeromonas was positively correlated with the removal of COD and ammonia nitrogen
      (NH4+-N). Besides, Methyloversatilis became dominant only in 20 mg/L rhamnolipid
      treated groups and was positively correlated with VS. This study provides a novel
      and feasible strategy for treating poorly biodegradable wastewater by biofilm
      process with moderate amount of rhamnolipid.

PMID- 29454627
TI  - Changes in salsolinol production and salsolinol synthase activity in Parkinson's
      disease model.
AB  - Salsolinol is an endogenous neurotoxin derived from dopamine, and has been proved
      to cause the apoptosis of the dopaminergic neurons involved in the pathogenesis
      of Parkinson's disease (PD). Salsolinol synthase is the key enzyme in the
      biosynthesis of salsolinol, and its activity exists in most regions of rat brain.
      However, the activity distribution and its catalyzed function in vivo are still
      unknown. On the basis of the chromatographic assay established previously, we
      investigated the activity of salsolinol synthase and salsolinol production in
      both cell and rat model of PD induced by 6-hydroxydopamine (6-OHDA). The results
      show that the enzymatic activity increases in cell model and in the striatum
      region of PD rat brain. Nevertheless, there is a reduction of activity in
      hippocampus, cortex, and midbrain of PD model when compared with control.
      Conversely, the level of salsolinol was significantly increased in the midbrain
      region. Together, these results indicate the relationship between the oxidative
      stress induced by 6-OHDA and the activity of salsolinol synthase, suggesting the
      correlation of the endogenous neurotoxin and Parkinson's disease. Further
      research will provide more evidence and clarity on the function of Sal synthase.

PMID- 29454629
TI  - Postoperative pain and analgesia administration in children after urological
      outpatient procedures.
AB  - INTRODUCTION: There are limited data about pain patterns, analgesic requirements
      and factors predicting opioid requirements of children undergoing outpatient
      urologic surgery. This prospective study aimed to assess recovery profiles and
      pain medication requirements. METHODS: Patients between 6 months and 12 years of
      age were recruited prospectively between December 2013 and June 2014. Demographic
      and operative characteristics were collected. Following discharge home, the
      parents were asked to administer both acetaminophen and ibuprofen Q6H at a weight
      adjusted dose, based on a schedule, until the end of postoperative day 2, and to
      administer the medication as required on postoperative day 3. Pain severity was
      recorded using validated pain scores (Face, Legs, Activity, Cry,
      Consolability/Parents' Postoperative Pain Measurement). A morphine prescription
      was provided for breakthrough pain. A Likert scale was used to assess parent's
      satisfaction with the pain management. RESULTS: A total of 249 patients were
      recruited, 111 patients (45%) returned appropriately completed surveys and were
      included in the final analysis. Mean age was 44.1 months (SD = 37.3). The
      performed procedures were orchidopexy (31), hypospadias repair (26),
      hernia/hydrocele repair (15), Fowler-Stephens procedure (13), meatoplasty (7),
      phalloplasty (4), scrotoplasty (1), circumcision (7), and diagnostic laparoscopy
      (5). After discharge home 17 patients (15.3%) received morphine. Mean utilization
      of non-opioid analgesia was 79% on postoperative day 1, 67% on day 2, 36% on day
      3, and 2% on day 4. Parental satisfaction was high (92.0% satisfied/very
      satisfied). No patient, anaesthetic or surgical factors were associated with
      opioid use or prolonged need for postoperative analgesia. CONCLUSION: The
      combination of scheduled non-opioid medications for maintenance and opioids for
      breakthrough pain provided satisfactory pain control after outpatient urologic
      surgery in children. There were no specific patient, anesthetic or surgical
      factors that predicted postoperative opioid requirements.

PMID- 29454628
TI  - Tunica vaginalis flap for salvaging testicular torsion: A matched cohort
      analysis.
AB  - INTRODUCTION: In testicular torsion, ischemia time from pain onset impacts
      testicular salvage. A tunica albuginea fasciotomy to relieve compartment pressure
      followed by a tunica vaginalis flap (TVF) may enhance salvage. OBJECTIVE: To
      define the optimal window of ischemia time during which TVF may be most
      beneficial to avoid orchiectomy. STUDY DESIGN: A retrospective cohort study of
      males presenting with testicular torsion at a single tertiary-care institution
      from January, 2003 to March, 2017. Ischemia time was defined as duration of pain
      from onset to surgery. Because TVF would be an option to orchiectomy, and it was
      found that ischemia time was longer in testicles that underwent orchiectomy,
      matching was performed. Cases of torsion treated with TVF were matched 1:1 with
      cases treated with orchiectomy on age at surgery, and ischemia time. Outcomes
      included postoperative viability, defined as palpable testicular tissue with
      normal consistency, and atrophy, defined as palpable decrease in size relative to
      contralateral testicle. Sensitivity analyses were performed restricting to the
      subgroups with postoperative ultrasound, >6 months' follow-up, and additionally
      matching for degrees of twist. RESULTS: A total of 182 patients met eligibility
      criteria, of whom 49, 36, and 97 underwent orchiectomy, TVF, and septopexy alone,
      respectively. Median follow-up was 2.7 months; 26% of patients had postoperative
      ultrasound (61% of TVF group). In the orchiectomy, TVF, and septopexy groups,
      respectively, median ischemia times were 51, 11, and 8 h, postoperative viability
      rates were 0, 86, and 95%, and postoperative atrophy rates were 0, 68, and 24%.
      After matching, 32 patients with TVF were matched to 32 patients who underwent
      orchiectomy. In the TVF group, postoperative viability occurred in 95% (19/20) vs
      67% (8/12) of patients with ischemia times <=24 and >24 h, respectively. Atrophy
      occurred in 67% (12/18) vs 83% (10/12) of these same respective patients.
      Sensitivity analysis by ultrasound and longer follow-up found similar viability
      results, although atrophy rates were higher. Additional matching for degrees of
      twist showed lower viability and higher atrophy rates for increasing ischemia
      times. DISCUSSION: Patients who presented with testicular torsion with ischemia
      times <=24 h and who were being considered for orchiectomy may have benefitted
      most from TVF, albeit at high risk of atrophy. However, for ischemia times >24 h,
      TVF may still have preserved testicular viability in two-thirds of cases. A
      limitation was short follow-up. CONCLUSION: A TVF was a valid alternative to
      orchiectomy for torsed testicles, albeit with high testicular atrophy rates.

PMID- 29454630
TI  - Microsurgical anastomosis of renal vasculature in rats: A practical platform for
      acellular kidney transplantation.
AB  - End-stage renal disease is becoming a contemporary global concern with increasing
      prevalence. The available treatment strategies are limited to dialysis and renal
      transplantation. However, limited organ supply and autoimmune rejection are the
      shortcomings that limit widespread application of transplantation. Favorably,
      regenerative medicine is able to provide acellular natural scaffolds for renal
      transplantation. Experimental surgeries in animal models are a fundamental step
      in transplantation research. This video presents a practical method for
      transplantation of bilateral acellular kidneys in a rat model, which could serve
      as a key step for further research.

PMID- 29454631
TI  - Update on visual function and choroidal-retinal thickness alterations in
      Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative process that affects 7.5 million
      people around the world. Since 2004, several studies have demonstrated changes in
      various retinal layers in PD using optical coherence tomography (OCT). However,
      there are some discrepancies in the results of those studies. Some of them have
      correlated retinal thickness with the severity or duration of the disease,
      demonstrating that OCT measurements may be an innocuous and easy biomarker for PD
      progression. Other studies have demonstrated visual dysfunctions since early
      phases of the disease. Lastly, the most recent studies that use Swept Source OCT
      technology, have found choroidal thickness increase in PD patients and provide
      new information related to the retinal degenerative process in this disease. The
      aim of this paper is to review the literature on OCT and PD, in order to
      determine the altered retinal and choroidal parameters in PD and their possible
      clinical usefulness, and also the visual dysfunctions with higher impact in these
      patients.

PMID- 29454632
TI  - A case of Epstein-Barr virus-negative human immunodeficiency virus-related
      primary effusion lymphoma.
AB  - Primary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma
      associated with human herpesvirus-8. Most cases are co-infected with Epstein-Barr
      virus (EBV). The prognosis of PEL is extremely poor and no optimal treatment
      regimen has been established. We report a case of EBV-negative PEL in a 49-year
      old human immunodeficiency virus-positive man, presenting with massive bilateral
      pleural effusion.

PMID- 29454633
TI  - Long-term sequelae after lung abscess in children - Two tertiary centers'
      experience.
AB  - AIM: The aim of the study was to describe the epidemiology and clinical
      characteristic of children hospitalized with pneumonia complicated by lung
      abscess, as well as to evaluate the long-term sequelae of the disease. METHODS: A
      retrospective review of medical records of all patients treated for pulmonary
      abscess in two tertiary centers was undertaken. Pulmonary function tests and lung
      ultrasound were performed at a follow-up. RESULTS: During the study period, 5151
      children with pneumonia were admitted, and 49 (0.95%) cases were complicated with
      lung abscess. In 38 (77.5%) patients, lung abscess was treated solely with
      antibiotics, and in nine cases (16.3%) surgically. In 21 (51.21%) children
      complete radiological regression was documented. The mean time for radiological
      abnormalities regression was 84.14 +/- 51.57 days, regardless of the treatment
      mode. Fifteen patients were followed up at 61.6 +/- 28.3 months after discharge.
      Lung ultrasound revealed minor residual abnormalities: pleural thickening,
      subpleural consolidations and line B artefacts in 11 (73.3%) children. Pulmonary
      function tests results were abnormal in eight (53.3%) patients, the most frequent
      abnormality being hyperinflation. We did not find a restrictive disorder in any
      of the children. There were no deaths in our study. CONCLUSIONS: Lung abscess is
      a rare but severe complication of pneumonia in children. Most children recover
      uneventfully with no significant long-term pulmonary sequelae.

PMID- 29454634
TI  - Feminizing Genital Gender-Confirmation Surgery.
AB  - INTRODUCTION: For many patients with gender dysphoria, gender-confirmation
      surgery (GCS) helps align their physical characteristics with their gender
      identity and is a fundamental element of comprehensive treatment. This article is
      the 2nd in a 3-part series about the treatment of gender dysphoria. Non-operative
      management was covered in part 1. This section begins broadly by reviewing
      surgical eligibility criteria, benefits of GCS, and factors associated with
      regret for transgender men and women. Then, the scope narrows to focus on aspects
      of feminizing genital GCS, including a discussion of vaginoplasty techniques,
      complications, and sexual function outcomes. Part 3 features operative
      considerations for masculinizing genital GCS. AIM: To summarize the World
      Professional Association for Transgender Health's (WPATH) surgical eligibility
      criteria and describe how patients with gender dysphoria benefit from GCS,
      provide an overview of genital and non-genital feminizing gender-confirmation
      procedures, and review vaginoplasty techniques, preoperative considerations,
      complications, and outcomes. METHODS: A review of relevant literature through
      April 2017 was performed using PubMed. MAIN OUTCOME MEASURES: Review of
      literature related to surgical eligibility criteria for GCS, benefits of GCS, and
      surgical considerations for feminizing genitoplasty. RESULTS: Most transgender
      men and women who satisfy WPATH eligibility criteria experience improved quality
      of life, overall happiness, and sexual function after GCS; regret is rare. Penile
      inversion vaginoplasty is the preferred technique for feminizing genital GCS
      according to most surgeons, including the authors whose surgical technique is
      described. Intestinal vaginoplasty is reserved for certain scenarios. After
      vaginoplasty most patients report overall high satisfaction with their sexual
      function even when complications occur, because most are minor and easily
      treatable. CONCLUSION: GCS alleviates gender dysphoria for appropriately selected
      transgender men and women. Preoperative, intraoperative, and postoperative
      considerations of feminizing genital gender-confirmation procedures were
      reviewed. Hadj-Moussa M, Ohl DA, Kuzon WM. Feminizing Genital Gender-Confirmation
      Surgery. Sex Med Rev 2018;6:457-468.

PMID- 29454635
TI  - Sleep Behavior and EEG Oscillations in Aged Dp(16)1Yey/+ Mice: A Down Syndrome
      Model.
AB  - Down syndrome (DS) results from the triplication of genes located on human
      chromosome 21 (Hsa21). Though many cognitive and behavioral impairments are
      associated with DS, sleep disturbances remain poorly understood despite being a
      reported phenotype in approximately 60% of individuals diagnosed with DS. In this
      study, sleep and electroencephalography (EEG) oscillations were recorded from
      aged (12-14 mos.) Dp(16)1Yey/+ mice (Dp16), a mouse model of DS. We observed
      disrupted sleep demonstrated by increased activity during the dark phase and
      increased time awake at the expense of NREM sleep compared to wild-type mice. In
      addition, we found that Dp16 mice display significant differences in relative EEG
      power distribution among oscillation frequencies in both sleep and awake states.
      These results in Dp16 mice are consistent with sleep disturbances found in
      individuals with DS, and the abnormal EEG oscillations in aged Dp16 mice suggest
      a potential role for GABAergic activity in these sleep and EEG abnormalities.
      These sleep and EEG data reflect underlying differences in neuronal activity at
      the network level and thus are causative agents rather than merely symptoms of
      DS.

PMID- 29454636
TI  - Incisional hernia prevention and use of mesh. A narrative review.
AB  - Incisional hernias are a very common problem, with an estimated incidence around
      15-20% of all laparotomies. Evisceration is another important problem, with a
      lower rate (2.5-3%) but severe consequences for patients. Prevention of both
      complications is an essential objective of correct patient treatment due to the
      improved quality of life and cost savings. This narrative review intends to
      provide an update on incisional hernia and evisceration prevention. We analyze
      the current criteria for proper abdominal wall closure and the possibility to add
      prosthetic reinforcement in certain cases requiring it. Parastomal, trocar-site
      hernias and hernias developed after stoma closure are included in this review.

PMID- 29454637
TI  - Tools to study pathogen-host interactions in bats.
AB  - Bats are natural reservoirs for a variety of emerging viruses that cause
      significant disease in humans and domestic animals yet rarely cause clinical
      disease in bats. The co-evolutionary history of bats with viruses has been
      hypothesized to have shaped the bat-virus relationship, allowing both to exist in
      equilibrium. Progress in understanding bat-virus interactions and the isolation
      of bat-borne viruses has been accelerated in recent years by the development of
      susceptible bat cell lines. Viral sequences similar to severe acute respiratory
      syndrome corona virus (SARS-CoV) have been detected in bats, and filoviruses such
      as Marburg virus have been isolated from bats, providing definitive evidence for
      the role of bats as the natural host reservoir. Although viruses can be readily
      detected in bats using molecular approaches, virus isolation is far more
      challenging. One of the limitations in using traditional culture systems from non
      reservoir species is that cell types and culture conditions may not be compatible
      for isolation of bat-borne viruses. There is, therefore, a need to develop
      additional bat cell lines that correspond to different cell types, including less
      represented cell types such as immune cells, and culture them under more
      physiologically relevant conditions to study virus host interactions and for
      virus isolation. In this review, we highlight the current progress in
      understanding bat-virus interactions in bat cell line systems and some of the
      challenges and limitations associated with cell lines. Future directions to
      address some of these challenges to better understand host-pathogen interactions
      in these intriguing mammals are also discussed, not only in relation to viruses
      but also other pathogens carried by bats including bacteria and fungi.

PMID- 29454638
TI  - Testosterone Levels and Prostate Cancer Prognosis: Systematic Review and Meta
      analysis.
AB  - Androgen receptor is the major driver of and testosterone the natural growth
      factor of prostate cancer (PC). Studies exploring the relationship among
      circulating testosterone levels, PC aggressiveness, and patient prognosis showed
      contradictory results. We performed a comprehensive literature search for studies
      reporting the independent relationship between serum testosterone and prognosis
      of PC patients. Meta-analyses using random effects models were conducted to
      estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). We
      identified 25 articles that evaluated the prognostic value of testosterone in
      early-stage PC (8 studies), in advanced PC either before (4 studies) or during
      androgen deprivation therapy (ADT) (5 studies), and in castration-resistant PC (8
      studies). In early PC, serum testosterone level was not prognostic in terms of
      overall survival (HR = 1.03; 95% CI, 0.99-1.08; P = .19) and biochemical
      recurrence (HR = 0.99; 95% CI, 0.87-1.13; P = .93). In advanced PC, higher
      testosterone levels before ADT were associated with a reduced risk of death (HR =
      0.58; 95% CI, 0.45-0.74; P < .0001). During ADT, lower levels were associated
      with a reduced risk of death (HR = 0.48; 95% CI, 0.28-0.81; P = .006) and
      progression (HR = 0.59; 95% CI, 0.46-0.77; P < .0001). In castration-resistant PC
      patients, higher testosterone levels predicted a reduced risk of progression (HR
      = 0.33; 95% CI, 0.11-0.97; P = .04) but not of death (HR = 0.86; 95% CI, 0.69
      1.07; P = .18). The heterogeneity of the included studies is a major limitation
      of this meta-analysis. The relationship between circulating testosterone and PC
      prognosis varies in different clinical settings and according to ADT
      administration.

PMID- 29454639
TI  - Neutrophil-to-lymphocyte Ratio, Platelet-to-lymphocyte Ratio, and C-reactive
      Protein as New and Simple Prognostic Factors in Patients With Metastatic Renal
      Cell Cancer Treated With Tyrosine Kinase Inhibitors: A Systemic Review and Meta
      analysis.
AB  - BACKGROUND: Inflammation plays a crucial role in cancer development. In this
      study, we evaluate the prognostic values of systemic inflammation markers such as
      neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C
      reactive protein (CRP) for the progression-free survival and overall survival in
      patients with metastatic renal cell carcinoma treated with tyrosine kinase
      inhibitors. MATERIALS AND METHODS: PubMed and the Cochrane Library databases were
      searched for published studies on the effect of NLR, PLR, and CRP in patients
      with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.
      RESULTS: In the meta-analysis, NLR (hazard ratio [HR], 2.01; 95% confidence
      interval [CI], 1.27-3.18; P = .003) and PLR (HR, 6.96; 95% CI, 5.04-9.62; P <
      .001) had a significant influence on progression-free survival, whereas all
      considered proinflammatory markers had a significant impact on overall survival:
      NLR (HR, 2.14; 95% CI, 1.67-2.73; P < .001), PLR (HR, 14.67; 95% CI, 11.10-19.57;
      P < .001), and CRP (HR, 1.96; 95% CI, 1.26-3.05; P = .003). CONCLUSIONS:
      Inflammation markers such as NLR, PLR, and CRP are predictors of clinical outcome
      and could provide additional information to individualize treatment.

PMID- 29454640
TI  - Correction.

PMID- 29454641
TI  - Beyond the FRN: Broadening the time-course of EEG and ERP components implicated
      in reward processing.
AB  - Most reward-related electroencephalogram (EEG) studies focus exclusively on the
      feedback-related negativity (FRN, also known as feedback negativity or FN, medial
      frontal negativity or MFN, feedback error-related negativity or fERN, and reward
      positivity or RewP). This component is usually measured approximately 200-300 ms
      post-feedback at a single electrode in the frontal-central area (e.g., Fz or
      FCz). The present review argues that this singular focus on the FRN fails to
      leverage EEG's greatest strength, its temporal resolution, by underutilizing the
      rich variety of event-related potential (ERP) and EEG time-frequency components
      encompassing the wider temporal heterogeneity of reward processing. The primary
      objective of this review is to provide a comprehensive understanding of often
      overlooked ERP and EEG correlates beyond the FRN in the context of reward
      processing with the secondary goal of guiding future research toward multistage
      experimental designs and multicomponent analyses that leverage the temporal power
      of EEG. We comprehensively review reward-related ERPs (including the FRN,
      readiness potential or RP, stimulus-preceding negativity or SPN, contingent
      negative variation or CNV, cue-related N2 and P3, Feedback-P3, and late-positive
      potential or LPP/slow-wave), and reward-related EEG time-frequency components
      (changes in power at alpha, beta, theta, and delta bands). These
      electrophysiological signatures display distinct time-courses, scalp
      topographies, and reflect independent psychological processes during anticipatory
      and/or outcome stages of reward processing. Special consideration is given to the
      time-course of each component and factors that significantly contribute to
      component variation. Concluding remarks identify current limitations along with
      recommendations for potential important future directions.

PMID- 29454642
TI  - Moderate financial incentive does not appear to influence the P300 Concealed
      Information Test (CIT) effect in the Complex Trial Protocol (CTP) version of the
      CIT in a forensic scenario, while affecting P300 peak latencies and behavior.
AB  - Previous research indicated that the skin conductance response (SCR) of the
      Autonomic Nervous System (ANS) in the Concealed Information Test (CIT) is
      typically increased in subjects who are financially and otherwise incentivized to
      defeat the CIT (the paradoxical "motivational impairment" effect). This is not
      the case for RT-based CITs, nor for P300 tests based on the 3-stimulus protocol
      or Complex Trial Protocol for detection of cognitive malingering (although these
      are not the same as forensic CITs). The present report extends earlier studies of
      malingerers by running five groups of subjects (15-16 per group yielding 78
      total) in a mock crime (forensic) scenario: paid (to beat the test) and unpaid,
      instructed and uninstructed, and simply guilty. There was no evidence that the
      "CIT effect" (probe-minus-irrelevant P300 differences) differed among groups,
      although behavioral differences among groups were seen.

PMID- 29454643
TI  - Proprioceptive stimuli and habit formation: Interresponse time mediated behavior
      in CD-1 mice.
AB  - The consolidation of behavioral sequences into relatively ballistic habits is
      thought to involve the formation of stimulus - response associations. Typically,
      the stimuli in these associations are assumed to be exteroceptive, i.e., external
      to the organism. However, responses, themselves, also possess stimulus properties
      that can mediate behavior. Indeed, these "proprioceptive cues" have long been
      hypothesized to underlie habit formation (Hull, 1934a, 1934b). One such stimulus
      involves the time durations between responses - a stimulus termed interresponse
      time (IRT). We hypothesize that IRTs can come to serve as stimuli that
      differentially control response elements during habit formation. To examine this
      hypothesis we report on two experiments that asked whether CD-1 mice utilize IRTs
      to structure behavior in a two-choice environment. In experiment 1, eight mice
      were exposed to a free-operant concurrent variable-interval (VI) 30-s VI 60-s
      reinforcement schedule. We found that switch and stay responses were
      differentially correlated with IRT durations. In Experiment 2 we directly and
      differentially reinforced stay/switch responses based on IRT durations in a two
      lever procedure. For four of the subjects, the probability of receiving
      reinforcement after switch responses was proportional to IRT duration. For five
      of the subjects, these reinforcement probabilities were inversely proportional to
      IRT duration. Regardless, all of our subjects learned to emit IRT-mediated
      switching behavior that matched the reinforcement contingencies. Together,
      Experiments 1 and 2 provide the first evidence of which we are aware that IRTs
      can come to control sequential choice behavior in mice.

PMID- 29454644
TI  - Testing aggressive behaviour in a feeding context: Importance of ethologically
      relevant stimuli.
AB  - The choice of stimuli used in tests of animal behaviour can have a critical
      effect on the outcome. Here we report two experiments showing how different foods
      influenced aggressive behaviour in competition tests at weaning among littermates
      of the domestic cat. Whereas in Experiment 1 canned food elicited almost no overt
      competition, a piece of raw beef rib elicited clearly aggressive behaviour among
      littermates. In Experiment 2 the food stimuli were chosen to differ from raw beef
      rib in various combinations of taste/smell, texture and monopolizability. Kittens
      showed different levels of aggression in response to the five stimuli tested,
      which suggests that the strong effect of beef rib in eliciting aggressive
      behaviour was due to a complex combination of features. We suggest that using
      stimuli approximating the evolved, functional significance to the species
      concerned is more likely to result in robust, biologically relevant behaviours
      than more artificial stimuli.

PMID- 29454645
TI  - Characterization of CD4+ T cell-mediated cytotoxicity in patients with multiple
      myeloma.
AB  - Multiple myeloma (MM) is an incurable cancer characterized by the development of
      malignant plasma cells. The CD8 T cell-mediated cytotoxicity is considered a
      major player in antitumor immunity, but in MM patients, the CD8 T cells displayed
      senescence markers and were functionally impaired. To investigate whether
      cytotoxic CD4 T cells could act as a treatment alternative in MM, we examined the
      frequency and function of naturally occurring cytotoxic CD4 T cells in MM
      patients. The cytotoxic CD4 T cells were identified as granzyme-A, granzyme B-,
      and perforin-expressing CD4 T cells, and their frequencies were significantly
      upregulated in MM patients when compared with healthy controls. The frequencies
      of cytotoxic CD4 T cells in MM patients were not associated with the frequencies
      of cytotoxic CD8 T cells, but were negatively associated with disease severity.
      Interestingly, the expression levels of inhibitory molecules, including PD-1 and
      CTLA-4, were significantly lower in cytotoxic CD4 T cells than in cytotoxic CD8 T
      cells. When co-incubated with autologous CD38+CD138+ plasma cells, CD4 T cells
      were capable of eliminating plasma cells with varying degrees of efficacy. In MM
      patients, the frequency of circulating plasma cells was negatively correlated
      with the frequency of cytotoxic CD4 T cells. Therefore, CD4 T cell-mediated
      cytotoxicity existed naturally in MM patients and could potentially act as an
      option in antitumor therapies.

PMID- 29454646
TI  - Alteration of CCR6+CD95+CD4+ naive T cells in HIV-1 infected patients:
      Implication for clinical practice.
AB  - The profound deficiency of Th17 cells contributes to HIV disease progression. The
      mechanisms of their perturbation remain unclear. Recently, CCR6+CD95+CD4+ naive T
      cells (CCR6+CD95+CD4+ TNA), identified as pre-committed Th17 precursors, were
      recognized as a subpopulation of CD4+ T cells with stem cell properties.
      Following phenotypical identification, we evaluated their level in patients
      during chronic HIV infection and following antiretroviral therapy (ART) using
      flow cytometry. The levels of CCR6+CD95+CD4+ TNA were decreased during chronic
      HIV infection and correlated with CD4+ T cell counts. Immunological responders
      harbored higher frequency of CCR6+CD95+CD4+ TNA, which was associated with
      CD4/CD8 T cell ratio. Immunological non-responders with lower frequency of
      CCR6+CD95+CD4+ TNA failed to exhibit a correlation between CCR6+CD95+CD4+ TNA and
      CCR6+CD95+CD4+ TCM, and displayed elevated ratio of CCR6+CD95+CD4+ TCM/TNA. The
      number of CCR6+CD95+CD4+ TNA was increased following early ART. These findings
      shed light on the importance of targeting pre-committed Th17 precursors that
      enhance immune reconstitution.

PMID- 29454647
TI  - Dynamic plasticity of macrophage functions in diseased liver.
AB  - Liver macrophages attract increasing interest due to their crucial roles in
      homeostasis and hepatic diseases. Recent findings in mice and man suggest a
      remarkable phenotypic and functional diversity of liver macrophages. Kupffer
      cells, the subset of tissue resident macrophages with sentinel functions in
      liver, mainly arise from embryogenic precursors, whereas in injury, liver tissue
      is engrafted by monocyte-derived macrophages. Both principal macrophage
      populations respond to local or systemic signals and have substantial effects on
      reduction as well as aggravation of hepatic diseases. Despite contrasting
      functions of heterogeneous macrophage subsets in disease progression and
      regression, they may provide promising targets for novel therapeutic
      interventions in hepatology. Areas of intense research include their multifaceted
      roles in metabolic diseases (non-alcoholic steatohepatitis, NASH), fibrosis or
      liver cancer (hepatocellular or cholangiocellular carcinoma, HCC or CCA). We
      discuss recent findings on the origin, diversity and functional plasticity of
      liver macrophages in homeostasis and hepatic disease conditions.

PMID- 29454648
TI  - FOXP3 renders activated human regulatory T cells resistant to restimulation
      induced cell death by suppressing SAP expression.
AB  - Restimulation-induced cell death (RICD) is an apoptotic program that regulates
      effector T cell expansion, triggered by repeated stimulation through the T cell
      receptor (TCR) in the presence of interleukin-2 (IL-2). Although CD4+ regulatory
      T cells (Tregs) consume IL-2 and experience frequent TCR stimulation, they are
      highly resistant to RICD. Resistance in Tregs is dependent on the forkhead box P3
      (FOXP3) transcription factor, although the mechanism remains unclear. T cells
      from patients with X-linked lymphoproliferative disease (XLP-1), that lack the
      adaptor molecule SLAM-associated protein (SAP), are also resistant to RICD. Here
      we demonstrate that normal Tregs express very low levels of SAP compared to
      conventional T cells. FOXP3 reduces SAP expression by directly binding to and
      repressing the SH2D1A (SAP) promoter. Indeed, ectopic SAP expression restores
      RICD sensitivity in human FOXP3+ Tregs. Our findings illuminate the mechanism
      behind FOXP3-mediated RICD resistance in Tregs, providing new insight into their
      long-term persistence.

PMID- 29454649
TI  - Relationship between vectorcardiographic QRSarea, myocardial scar quantification,
      and response to cardiac resynchronization therapy.
AB  - PURPOSE: To investigate the relationship between vectorcardiography (VCG) and
      myocardial scar on cardiac magnetic resonance (CMR) imaging, and whether
      combining these metrics may improve cardiac resynchronization therapy (CRT)
      response prediction. METHODS: Thirty-three CRT patients were included. QRSarea,
      Tarea and QRSTarea were derived from the ECG-synthesized VCG. CMR parameters
      reflecting focal scar core (Scar2SD, Gray2SD) and diffuse fibrosis (pre-T1,
      extracellular volume [ECV]) were assessed. CRT response was defined as >=15%
      reduction in left ventricular end-systolic volume after six months' follow-up.
      RESULTS: VCG QRSarea, Tarea and QRSTarea inversely correlated with focal scar (R
      = -0.44--0.58 for Scar2SD, p <= 0.010), but not with diffuse fibrosis. Scar2SD,
      Gray2SD and QRSarea predicted CRT response with AUCs of 0.692 (p = 0.063), 0.759
      (p = 0.012) and 0.737 (p = 0.022) respectively. A combined ROC-derived threshold
      for Scar2SD and QRSarea resulted in 92% CRT response rate for patients with large
      QRSarea and small Scar2SD or Gray2SD. CONCLUSION: QRSarea is inversely associated
      with focal scar on CMR. Incremental predictive value for CRT response is achieved
      by a combined CMR-QRSarea analysis.

PMID- 29454650
TI  - Author's re'sponse to letter to the editor from Hayirlioglu M et al.

PMID- 29454651
TI  - Effects of Prophylactic Foscarnet on Human Herpesvirus-6 Reactivation and
      Encephalitis in Cord Blood Transplant Recipients: A Prospective Multicenter Trial
      with an Historical Control Group.
AB  - Cord blood transplantation (CBT) is a distinct risk factor for human herpesvirus
      6 (HHV-6) reactivation and HHV-6 encephalitis. In a prospective multicenter trial
      we investigated the effects of prophylactic foscarnet (90 mg/kg i.v. infusion
      from days 7 to 27 after CBT) on the occurrence of HHV-6 reactivation, HHV-6
      encephalitis, and acute graft-versus-host disease (aGVHD) in CBT recipients.
      Between 2014 and 2016, 57 patients were included in a foscarnet-prophylaxis
      group. Outcomes were compared with an historical control group who received CBT
      between 2010 and 2014 (standard-treatment group, n = 63). The cumulative
      incidence of high-level HHV-6 reactivation, defined as plasma HHV-6 DNA >= 104
      copies/mL, at 60 days after CBT was significantly lower in the foscarnet
      prophylaxis group than in the standard-treatment group (18.3% versus 57.3%, P <
      .001). Multivariate analysis revealed that myeloablative preconditioning and
      standard treatment were significant risk factors for high-level HHV-6
      reactivation. The cumulative incidence of HHV-6 encephalitis at 60 days after CBT
      was not different between the groups (foscarnet-prophylaxis group, 12.4%;
      standard-treatment group, 4.9%; P = .14). The cumulative incidences of grades II
      to IV and grades III to IV aGVHD at 60 days after CBT were not different between
      the groups (grades II to IV aGVHD: foscarnet-prophylaxis group, 42.0%; standard
      treatment group, 40.5%; P = .96; grades III to IV aGVHD: foscarnet-prophylaxis
      group, 14.5%; standard-treatment group, 14.5%; P = 1.00). In the setting of this
      study foscarnet significantly suppressed systemic HHV-6 reactivation in CBT
      recipients but failed to prevent the development of HHV-6 encephalitis.
      Suppression of HHV-6 reactivation by foscarnet did not show any effects against
      the incidence of aGVHD.

PMID- 29454652
TI  - Rapid one-step extraction method for the identification of molds using MALDI-TOF
      MS.
AB  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) has revolutionized fungal identification. Previously, we developed
      a MALDI-TOF MS mold extraction procedure and comprehensive database. While MALDI
      TOF MS has become routine in a few laboratories, it has not yet become
      widespread. A major obstacle is the lack of a simple, reproducible and uniform
      protein extraction procedure. In this study, we developed and validated a rapid
      one-step protein extraction protocol for filamentous fungi. Excised molds were
      placed into tubes containing zirconia-silica beads and extraction solution
      without washing or ethanol inactivation steps. Extraction solutions containing
      different ratios of acetonitrile and formic acid were evaluated. Samples were
      then processed using a PowerLyzer high power bead based homogenizer and
      supernatants spotted for MALDI-TOF MS. The rapid method was evaluated
      prospectively and in parallel to our current mold extraction protocol for 3
      months. Analysis of 106 clinical mold isolates resulted in an improved
      performance and a decrease in extraction time by 30 minutes to a total of 5
      minutes of hands-on time. Acceptable identification scores (>= 2.00) were
      achieved for up to 63.0% of mold isolates by the rapid method compared with 52.8%
      of isolates by the current routine protocol. Score comparisons between duplicate
      spots showed higher reproducibility of the rapid method as compared to the
      routine method. The rapid extraction method allows efficient analysis of clinical
      mold isolates both in scheduled batch runs and on an in-demand basis while
      providing a simple starting platform for laboratories adopting MALDI-TOF MS for
      mold identification.

PMID- 29454653
TI  - Diagnostic yield of real-time polymerase chain reaction in the diagnosis of
      intrapartum maternal rectovaginal colonization by group B Streptococcus: a
      systematic review with meta-analysis.
AB  - Group B Streptococcus is the leading etiologic factor of neonatal sepsis.
      Intrapartum real-time polymerase chain reaction (RT-PCR) may allow faster and
      more accurate detection of maternal colonization. The aim of this study was to
      determine the sensitivity and specificity of RT-PCR when compared to the
      reference standard culture in selective broth media collected from rectovaginal
      tract from laboring women. We selected 15 studies that included 6368 women.
      Papers selection, data extraction, and quality assessment were carried out by two
      independent researchers. The prevalence of maternal colonization was 23.8% by RT
      PCR and 22.1% by culture. The meta-analysis demonstrated an RT-PCR sensitivity of
      93.7% (CI 92.1-95.3), and specificity of 97.6% (CI 97.0-98.1). This result is
      above the cutoff point defined by the Centers for Disease Control and Prevention
      for clinical usefulness. In conclusion, RT-PCR for GBS screening in labor ward is
      a promising tool; however, further well-designed studies to justify its use are
      needed.

PMID- 29454655
TI  - Neurogenetic Approaches to Stress and Fear in Humans as Pathophysiological
      Mechanisms for Posttraumatic Stress Disorder.
AB  - In this review article, genetic variation associated with brain responses related
      to acute and chronic stress reactivity and fear learning in humans is presented
      as an important mechanism underlying posttraumatic stress disorder. We report
      that genes related to the regulation of the hypothalamic-pituitary-adrenal axis,
      as well as genes that modulate serotonergic, dopaminergic, and neuropeptidergic
      functions or plasticity, play a role in this context. The strong overlap of the
      genetic targets involved in stress and fear learning suggests that a dimensional
      and mechanistic model of the development of posttraumatic stress disorder based
      on these constructs is promising. Genome-wide genetic analyses on fear and stress
      mechanisms are scarce. So far, reliable replication is still lacking for most of
      the molecular genetic findings, and the proportion of explained variance is
      rather small. Further analysis of neurogenetic stress and fear learning needs to
      integrate data from animal and human studies.

PMID- 29454654
TI  - Invasive pulmonary aspergillosis and influenza co-infection in immunocompetent
      hosts: case reports and review of the literature.
AB  - Invasive pulmonary aspergillosis (IPA) is classically considered an illness of
      severely immunocompromised patients with limited host defenses. However, IPA has
      been reported in immunocompetent but critically ill patients. This report
      describes two fatal cases of pathologically confirmed IPA in patients with
      influenza in the intensive care unit. One patient had influenza B infection,
      whereas the other had influenza A H1N1. Both patients died despite broad-spectrum
      antimicrobials, mechanical ventilation, and vasopressor support. Microscopic and
      histologic postmortem examination confirmed IPA. Review of the English language
      and foreign literature indicates that galactomannan antigen testing and classic
      radiologic findings for IPA may not be reliable in immunocompetent patients.
      Respiratory cultures which grow Aspergillus species in critically ill patients,
      particularly those with underlying influenza infection, should not necessarily be
      disregarded as contaminants or colonizers. Further research is needed to better
      understand the immunological relationship between influenza and IPA for improved
      prevention and treatment of influenza and Aspergillus co-infections.

PMID- 29454656
TI  - Rhythm and orthopedics: The effect of music therapy in cast room procedures, a
      prospective clinical trial.
AB  - INTRODUCTION: Cast room procedures generally cause anxiety in patients. Anxiety
      complicates the procedure as well as increases the risk of a complication.
      Listening to music was found to be the safest and most common non-drug treatment
      method. The aim of this study is to evaluate the effect of listening to music on
      adult patients in cast room procedures. This study points out the relation
      between anxiety and anxiety relevant cardiac arrhythmia. MATERIALS AND METHODS:
      The study was performed on 199 patients with stable general condition, aged above
      18. The patients were divided into two groups. Randomization method used in the
      study was coin flip. The first group (Group 1) listened to music during cast room
      procedures whereby the second group (Group 2) did not listen to music. Length of
      the procedure, complication, blood pressure and heart rate evaluations before and
      after the procedure, Visual Analogue Scale (VAS scores for pain), State-Trait
      Anxiety Inventory (STAI) anxiety score, patient satisfaction, willingness of the
      patient to repeat the procedure, P wave dispersion (Pd) and corrected QT interval
      dispersion (QTcd) as electrocardiographic arrhythmia predictors were evaluated.
      The Clinical Research Ethics Committee approval was obtained for this study.
      RESULTS: Significant difference was shown between the two groups for the
      following criteria: VAS scores (p = 0.005), anxiety scores (p = 0.032),
      processing time (p = 0.027), and QTcd values (p = 0.031). Patient satisfaction (p
      < 0.001) and willingness to repeat the procedure (p < 0.001) were higher for the
      group who listened to music. No significant difference in Pd values, blood
      pressure and heart rate was reported within the groups. CONCLUSION: Music therapy
      is a non-invasive, safe, nonpharmacologic, anxiolytic, and analgesic treatment.
      Music therapy should become standard protocol in cast room procedures. One of the
      most important achievements of this study was the fact that music decreases
      anxiety and anxiety-related cardiac arrhythmia. Therefore, conducting further
      prospective studies including high cardiac risk patients especially with
      arrhythmia is crucial.

PMID- 29454657
TI  - Monitoring brain neuronal activity with manipulation of cardiac events in a
      freely moving rat.
AB  - Behavioral and cognitive studies have demonstrated that brain functions are
      affected by the activity states of the peripheral organs, such as the cardiac and
      respiratory systems. However, detailed neurophysiological mechanisms underlying
      the body-brain interactions remain unknown. In this study, we developed a method
      for manipulating activity levels of the heart using direct cardiac stimulation
      and vagus nerve stimulation that can be combined with recording cerebral local
      field potentials using a microdrive system, electrocardiograms, electromyograms,
      in a freely moving rat. With this method, the electrical stimulation to the heart
      increases heart rates up to 14 Hz, whereas the vagus nerve stimulation decreases
      heart rates to 3 Hz. Transient electrical artifacts arising from the peripheral
      stimulation are not contaminated in cortical local field potential signals low
      pass filtered at 150 Hz and distinguishable from extracellular multiunit signals.
      The technique will contribute to understanding the neurophysiological correlate
      of mind-body associations in health and disease.

PMID- 29454658
TI  - Return to the Operating Room after Macular Surgery: IRIS Registry Analysis.
AB  - PURPOSE: To investigate the rate of return to the operating room after vitrectomy
      surgery to treat macular hole or epiretinal membrane. DESIGN: A retrospective
      registry cohort. PARTICIPANTS: Individuals receiving care in ophthalmology
      practices participating in the Academy IRIS (Intelligent Research in Sight)
      Registry. METHODS: Data from the IRIS Registry were analyzed for patients who
      underwent vitrectomy for macular holes or epiretinal membranes. Cases were
      identified by the combination of International Classification of Diseases, 9th
      revision code (362.54, 362.56) and a current procedural terminology (CPT) code
      for vitrectomy surgery between January 1, 2013 and June 30, 2017. MAIN OUTCOME
      MEASURES: The eyes that underwent additional eye surgery within 1 year after
      initial vitrectomy for macular hole or epiretinal membrane were identified, as
      was the nature of the additional procedures per CPT code. RESULTS: A total of 41
      475 eyes underwent vitrectomy for macular hole and 73 219 eyes underwent
      vitrectomy for epiretinal membrane during the study period. In the macular hole
      group, 7573 had a second surgery within 1 year, and 2827 (6.8%) had a second
      surgery that was not cataract related. In the epiretinal membrane group, 12 433
      had a second surgery within 1 year, 4022 (5.5%) of which were not cataract
      related. In the macular hole group, 4.6% of eyes returned to the operating room
      for another macular hole repair surgery, and 2.0% returned for retinal detachment
      repair. In the epiretinal membrane group, 1.4% returned for a second vitrectomy
      with membrane stripping, and 2.5% returned for retinal detachment repair.
      CONCLUSIONS: This registry-based study encompassed a large number of patients but
      was limited by the inaccessibility of some information and the potential for
      inaccurate medical records or coding, as it obtained data from multiple
      electronic health records entities. Excluding cataract surgery, approximately 6%
      of eyes that underwent vitrectomy to address macular hole or epiretinal membrane
      returned for a second ophthalmic procedure within a year. In the macular hole
      group, most secondary non-cataract surgeries were for another macular hole repair
      procedure. For both macular holes and epiretinal membranes, approximately 2% of
      eyes required retinal detachment repair surgery within 1 year.

PMID- 29454659
TI  - Predicting Visual Acuity by Using Machine Learning in Patients Treated for
      Neovascular Age-Related Macular Degeneration.
AB  - PURPOSE: To predict, by using machine learning, visual acuity (VA) at 3 and 12
      months in patients with neovascular age-related macular degeneration (AMD) after
      initial upload of 3 anti-vascular endothelial growth factor (VEGF) injections.
      DESIGN: Database study. PARTICIPANTS: For the 3-month VA forecast, 653 patients
      (379 female) with 738 eyes and an average age of 74.1 years were included. The
      baseline VA before the first injection was 0.54 logarithm of the minimum angle of
      resolution (logMAR) (+/-0.39). A total of 456 of these patients (270 female, 508
      eyes, average age: 74.2 years) had sufficient follow-up data to be included for a
      12-month VA prediction. The baseline VA before the first injection was 0.56
      logMAR (+/-0.42). METHODS: Five different machine-learning algorithms
      (AdaBoost.R2, Gradient Boosting, Random Forests, Extremely Randomized Trees, and
      Lasso) were used to predict VA in patients with neovascular AMD after treatment
      with 3 anti-VEGF injections. Clinical data features came from a data warehouse
      (DW) containing electronic medical records (41 features, e.g., VA) and
      measurement features from OCT (124 features, e.g., central retinal thickness).
      The VA of patient eyes excluded from machine learning was predicted and compared
      with the ground truth, namely, the actual VA of these patients as recorded in the
      DW. MAIN OUTCOME MEASURES: Difference in logMAR VA after 3 and 12 months upload
      phase between prediction and ground truth as defined. RESULTS: For the 3-month VA
      forecast, the difference between the prediction and ground truth was between 0.11
      logMAR (5.5 letters) mean absolute error (MAE)/0.14 logMAR (7 letters) root mean
      square error (RMSE) and 0.18 logMAR (9 letters) MAE/0.2 logMAR (10 letters) RMSE.
      For the 12-month VA forecast, the difference between the prediction and ground
      truth was between 0.16 logMAR (8 letters) MAE/0.2 logMAR (10 letters) RMSE and
      0.22 logMAR (11 letters) MAE/0.26 logMAR (13 letters) RMSE. The best performing
      algorithm was the Lasso protocol. CONCLUSIONS: Machine learning allowed VA to be
      predicted for 3 months with a comparable result to VA measurement reliability.
      For a forecast after 12 months of therapy, VA prediction may help to encourage
      patients adhering to intravitreal therapy.

PMID- 29454660
TI  - Development and Course of Scars in the Comparison of Age-Related Macular
      Degeneration Treatments Trials.
AB  - PURPOSE: To describe risk factors for scar formation and changes to fibrotic scar
      through 5 years in the Comparison of Age-related Macular Degeneration Treatments
      Trials (CATT). DESIGN: Multicenter, prospective cohort study. PARTICIPANTS: A
      total of 1061 subjects in CATT. METHODS: Color photographic and fluorescein
      angiographic images from baseline and 1, 2, and 5 years were evaluated. Incidence
      of scar formation was estimated with Kaplan-Meier curves. Risk factors were
      assessed with Cox regression models. MAIN OUTCOME MEASURES: Scar formation,
      fibrotic scar area, and macular atrophy associated with fibrotic scar
      ("atrophy"). RESULTS: Cumulative proportion of eyes with scar was 32%, 46%, and
      56% at years 1, 2, and 5, respectively. Baseline factors associated with
      increased risk (adjusted hazards ratio [aHR] and 95% confidence interval [CI])
      were classic choroidal neovascularization (CNV) (aHR, 4.49; 95% CI, 3.34-6.04)
      versus occult, hemorrhage >1 disc area (DA) (aHR, 2.28; 95% CI, 1.49-3.47) versus
      no hemorrhage, retinal thickness >212 MUm (aHR, 2.58; 95% CI, 1.69-3.94) versus
      <120 MUm, subretinal tissue complex thickness >275 MUm (aHR, 2.64; 95% CI, 1.81
      3.84) versus <=75 MUm, subretinal fluid thickness >25 MUm (aHR, 1.31; 95% CI,
      0.97-1.75) versus no fluid, visual acuity (VA) in fellow eye 20/20 (aHR, 1.72;
      95% CI, 1.25-2.36) versus 20/50 or worse, retinal pigment epithelium elevation
      absence (aHR, 1.71; 95% CI, 1.21-2.41), and subretinal hyperreflective material
      (aHR, 1.72; 95% CI, 1.25-2.36). Among 68 eyes that developed fibrotic scar at
      year 1, VA decreased by a mean of additional 13 letters between years 1 and 5.
      Mean scar area was 1.2, 1.2, and 1.9 DA at 1, 2, and 5 years, respectively.
      Atrophy was present in 18%, 24%, and 54% of these eyes at years 1, 2, and 5,
      respectively; the mean areas were 1.6, 2.0, and 3.1 DA, respectively. Atrophy
      replaced fibrotic scar in 8 eyes at year 5. There was no significant correlation
      between scar growth and atrophy growth. The rate of growth for both was similar
      between the clinical trial and observation periods. CONCLUSIONS: Several
      morphologic features, including classic CNV and large hemorrhage, are associated
      with scar formation. Rate of new scar formation declined after 2 years. Most
      fibrotic scars and accompanying macular atrophy expanded over time, reducing VA.

PMID- 29454662
TI  - Fecal markers of intestinal inflammation and intestinal permeability are elevated
      in Parkinson's disease.
AB  - BACKGROUND/OBJECTIVE: Intestinal inflammation and increased intestinal
      permeability (both possibly fueled by dysbiosis) have been suggested to be
      implicated in the multifactorial pathogenesis of Parkinson's disease (PD). The
      objective of the current study was to investigate whether fecal markers of
      inflammation and impaired intestinal barrier function corroborate this pathogenic
      aspect of PD. METHODS: In a case-control study, we quantitatively analyzed
      established fecal markers of intestinal inflammation (calprotectin and
      lactoferrin) and fecal markers of intestinal permeability (alpha-1-antitrypsin
      and zonulin) in PD patients (n = 34) and controls (n = 28, group-matched for age)
      by enzyme-linked immunosorbent assay. The study design controlled for potential
      confounding factors. RESULTS: Calprotectin, a fecal marker of intestinal
      inflammation, and two fecal markers of increased intestinal permeability (alpha-1
      antitrypsin and zonulin) were significantly elevated in PD patients compared to
      age-matched controls. Lactoferrin, as a second fecal marker of intestinal
      inflammation, showed a non-significant trend towards elevated concentrations in
      PD patients. None of the four fecal markers correlated with disease severity, PD
      subtype, dopaminergic therapy, or presence of constipation. CONCLUSIONS: Fecal
      markers reflecting intestinal inflammation and increased intestinal permeability
      have been primarily investigated in inflammatory bowel disease so far. Our data
      indicate that calprotectin, alpha-1-antitrypsin and zonulin could be useful non
      invasive markers in PD as well. Even though these markers are not disease
      specific, they corroborate the hypothesis of an intestinal inflammation as
      contributing factor in the pathogenesis of PD. Further investigations are needed
      to determine whether calprotectin, alpha-1-antitrypsin and zonulin can be used to
      define PD subgroups and to monitor the effect of interventions in PD.

PMID- 29454663
TI  - Novel PLA2G6 mutations and clinical heterogeneity in Chinese cases with
      phospholipase A2-associated neurodegeneration.
AB  - INTRODUCTION: Phospholipase A2-associated neurodegeneration (PLAN) is an
      autosomal recessive movement disorder with abnormal iron deposition in basal
      ganglia, substantial nigra and adjacent areas, and cerebellar atrophy. It is
      caused by PLA2G6 mutations and comprises three phenotypes. We aimed to
      investigate genetic mutations in patients with predominantly extrapyramidal
      symptoms. METHODS: Eighteen Chinese patients with early onset of extrapyramidal
      symptoms were identified and underwent targeted next-generation sequencing,
      followed by Sanger sequencing. Detailed clinical and radiological features are
      presented. Prediction software was used to evaluate the pathogenicity of the
      identified variants. RESULTS: We identified 7 PLA2G6 variants including five
      known variants (c.668C > T, c.991G > T, c.1117G > A, c.1982C > T, and c.2218G >
      A) and two novel variants (c.1511C > T, and c.1915G > A) in four index cases.
      Among them, three cases had initial symptoms of difficulty walking or gait
      disturbance around the age of 30, and one case and his sibling developed mental
      handicap at age 7. Two cases exhibited a phenotype of "early parkinsonism" and
      the other two cases mimicked a phenotype of "hereditary spastic paraplegia
      (HSP)". Iron deposition in globus pallidus and substantia nigra was seen in three
      cases. Cerebellar atrophy was present in all four cases. CONCLUSIONS: Our study
      expands the mutation spectrum of the PLA2G6 gene and further supports the
      hypothesis that PLA2G6 mutations are associated with a continuous clinical
      spectrum from PLAN to HSP.

PMID- 29454664
TI  - Survey of midwives' perinatal mental health knowledge, confidence, attitudes and
      learning needs.
AB  - BACKGROUND: Midwives have a primary role in facilitating the first stage of
      perinatal mental health risk reduction through inquiring about perinatal mental
      health, identifying risk factors and current perinatal mental health problems,
      providing support or crisis intervention, referring for treatment and decreasing
      stigmatisation. AIMS: The aims of this study were to determine midwives' (a)
      knowledge of and confidence to identify and manage perinatal mental health
      problems, (b) attitudes towards women who experience severe mental illness and
      (c) perceived learning needs. DESIGN: A cross-sectional survey design. METHODS:
      The study was conducted between September 2016 and April 2017 in seven Maternity
      services in the Republic of Ireland with a purposeful non-random convenience
      sample of midwives (n=157). Data was anonymously collected utilising the
      Perinatal Mental Health Questionnaire, the Mental Illness: Clinician's Attitudes
      scale and the Perinatal Mental Health Learning Needs questionnaire. FINDINGS:
      Midwives indicated high levels of knowledge (71.1%) and confidence (72%) in
      identifying women who experience depression and anxiety however, they reported
      less confidence in caring (43.9%) for women. Only 17.8% (n=28) of midwives felt
      equipped to support women whilst 15.3% (n=24) reported having access to
      sufficient information. Midwives desire education on the spectrum of perinatal
      mental health problems. The mean score for the Mental Illness: Clinician's
      Attitudes scale was 36.31 (SD=7.60), indicating positive attitudes towards women
      with severe mental illness. CONCLUSION: Midwives require further education on
      perinatal mental health across cultures with a skill focus and which explores
      attitudes delivered in a study day format.

PMID- 29454661
TI  - Rethinking Phagocytes: Clues from the Retina and Testes.
AB  - Specialized phagocytes are a newly appreciated classification of phagocyte that
      currently encompasses Sertoli cells (SCs) of the testes and the retinal pigment
      epithelial cells (RPE) of the retina. While these cells support very different
      tissues, they have a striking degree of similarity both as phagocytes and in ways
      that go beyond cell clearance. The clearance of apoptotic germ cells, cell
      debris, and used photoreceptor outer segments are critical functions of these
      cells, and the unique nature of their clearance events make specialized
      phagocytes uniquely suited for studying the larger implications of cell clearance
      in vivo. The shared functions of specialized phagocytes could provide novel
      insights into how phagocytosis impacts tissue homeostasis and immune modulation.
      In this review, we examine the remarkable similarities between SCs and RPE as
      specialized phagocytes and the physiological effects of cell clearance within a
      tissue.

PMID- 29454665
TI  - Women's choice of maternal healthcare in Parung, West Java, Indonesia: Midwife
      versus traditional birth attendant.
AB  - BACKGROUND: In the 1990s, the Indonesian government launched programmes to train
      traditional birth attendants (TBAs) and increase the number of midwives. AIM: To
      identify and compare the factors that influence women's choice of a midwife or a
      TBA for maternal healthcare in Indonesia. METHODS: This study used a descriptive
      design for comparing women's choice of maternal healthcare. The participants were
      (1) married women, (2) experienced birth within two years, (3) living in a rural
      or urban village, and (4) capable of communicating in the Indonesia language.
      Three instruments were used: (1) traditional belief questionnaire, (2) preference
      for caregiver questionnaire, and (3) women-centered care (WCC) questionnaire
      which measured women's perceptions of care that they received during pregnancy.
      FINDINGS: A total of 371 women participated in this study. All these subjects
      answered based on their most recent birth within the last two years. Of the 371
      women, 207 (55.8%) chose a midwife and 164 (44.2%) chose a TBA for giving birth.
      Women choosing midwives were generally satisfied and perceived receiving WCC.
      Factors determining choice were (1) women's background, (2) perception of WCC,
      (3) satisfaction, (4) choice of antenatal care (ANC), (5) family encouragement,
      and (6) traditional beliefs. DISCUSSION: The choice of caregivers was determined
      by not only education, parity, usual source of healthcare payment, and family
      encouragement but also traditional beliefs. CONCLUSION: Indonesian women's choice
      of a midwife instead of a TBA for their maternal healthcare resulted in a higher
      satisfaction of care and more ANC visits.

PMID- 29454666
TI  - Right atrium enlargement predicts clinically significant supraventricular
      arrhythmia in patients with pulmonary arterial hypertension.
AB  - BACKGROUND: Right atrial (RA) enlargement is a common finding in patients with
      pulmonary arterial hypertension (PAH) and an important predictor of mortality,
      however its relation to the risk of atrial arrhythmias has not been assessed.
      OBJECTIVES: To assess whether RA enlargement is associated with supraventricular
      arrhythmias (SVA) and whether it predicts new clinically significant SVA (csSVA).
      METHODS: Patients with PAH were recruited between January 2010 and December 2014
      and followed until January 2017. csSVA was diagnosed if it resulted in
      hospitalization. To assess predictors of new csSVA, only patients without a
      history of SVA at baseline were analyzed. RESULTS: Among 97 patients, any SVA was
      observed in 45 (46.4%) and included permanent atrial fibrillation(AF, n = 8),
      paroxysmal AF (n = 10), permanent atrial flutter (AFl, n = 1), paroxysmal AFl (n
      = 2) or other types of supraventricular tachycardia (n = 24). Patients with SVA
      as compared to patients without SVA were characterized by older age, lower
      distance in a 6-minute test, higher NT-proBNP, higher RA area index (RAai), left
      atrial area index, mean right atrial pressure (mRAP) and were more commonly
      treated with beta-blocker. Eighty five patients who were in sinus rhythm at
      baseline assessment and had no history of significant SVA were observed for 37 +/
      19.9 months. During that time csSVA occurred in 15.3%. In univariate models, the
      occurrence of csSVA were predicted by age, right ventricular ejection fraction,
      right ventricular end diastolic index, RAai and mRAP, but in multivariate model
      only RAai remained significant predictor for csSVA (HR of 1.23, 95%CI: 1.11-1.36,
      p < 0.001). The optimal threshold for RA enlargement as discriminator of csSVA
      was 21.7 cm2/m2. CONCLUSIONS: In PAH patients RA enlargement is associated with
      increased prevalence of SVA. RAai is an independent predictor of hospitalization
      due to csSVA.

PMID- 29454668
TI  - High level production of a recombinant acid stable exoinulinase from Aspergillus
      kawachii.
AB  - Exoinulinases-enzymes extensively studied in recent decades because of their
      industrial applications-need to be produced in suitable quantities in order to
      meet production demands. We describe here the production of an acid-stable
      recombinant inulinase from Aspergillus kawachii in the Pichia pastoris system and
      the recombinant enzyme's biochemical characteristics and potential application to
      industrial processes. After an appropriate cloning strategy, this genetically
      engineered inulinase was successfully overproduced in fed-batch fermentations,
      reaching up to 840 U/ml after a 72-h cultivation. The protein, purified to
      homogeneity by chromatographic techniques, was obtained at a 42% yield. The
      following biochemical characteristics were determined: the enzyme had an optimal
      pH of 3, was stable for at least 3 h at 55  degrees C, and was inhibited in
      catalytic activity almost completely by Hg+2. The respective Km and Vmax for the
      recombinant inulinase with inulin as substrate were 1.35 mM and 2673
      MUmol/min/mg. The recombinant enzyme is an exoinulinase but also possesses
      synthetic activity (i. e., fructosyl transferase). The high level of production
      of this recombinant plus its relevant biochemical properties would argue that the
      process presented here is a possible recourse for industrial applications in
      carbohydrate processing.

PMID- 29454667
TI  - PTEN expression in astrocytic processes after spinal cord injury.
AB  - The role of the Rho/ROCK/PTEN signaling pathway in the regulation of astrocyte
      function for consolidation/stabilization of the synapse has not been thoroughly
      studied. In this study, the expression of phosphatase and tensin homolog deleted
      on chromosome 10 (PTEN) in GFAP-positive astrocytic processes in the ventral
      horns (VH) of the rat spinal cord has been evaluated in the normal condition and
      in a delayed period (30 days) after dosed contusion spinal cord injury (SCI) in
      caudal thoracic segments. In intact rats and at 30 days post-injury (dpi), semi
      quantitative immunohistochemical analysis showed that there is approximately 2
      folds less synaptophysin reactivity in the motoneuron perikarya than outside the
      perikarya, i.e., on dendritic spines, in the VH area. At 30 dpi, the square
      occupied by synaptophysin reactivity on the motoneuron perikarya and dendritic
      spines decreased ~2.4 and ~2.1 folds, respectively. Western blotting of the
      postsynaptic density protein 95 (PSD95) showed a decreased amount in the area of
      injury of ~3 folds at 30 dpi. Expression of GFAP in the astrocytic processes
      around the synaptophysin spots (APAS) was less than in the astrocytic processes
      that were located at distance from the synapses (APFS) both in the intact and SCI
      groups. In the APAS, the expression level of PTEN increased significantly after
      SCI. In these astrocytic processes, the PTEN expression level was significantly
      higher than in the APFS for both the intact and SCI rats. In the intact spinal
      cord, different PTEN expression levels were detected both in APAS and APFS. This
      may be due to the varying degree of integration of PTEN in the membrane
      compartment of astrocyte stem processes and possibly the increased delivery of
      PTEN from the GFAP-positive stem into fine GFAP-negative peripheral processes.
      The observed shifts after SCI reflect the imbalance in the mechanisms of synaptic
      plasticity after injury. Thus, strategies that have been developed for the
      deletion or knockdown of the PTEN gene are quite promising.

PMID- 29454669
TI  - Rabbits and the Specious Origins of Domestication.
AB  - Rabbits are commonly thought to have been domesticated in ~AD600 by French monks.
      Using historical and archaeological records, and genetic methods, we demonstrate
      that this is a misconception and the general inability to date domestication
      stems from both methodological biases and the lack of appreciation of
      domestication as a continuum.

PMID- 29454670
TI  - Ultrasonography and detection of subclinical joints and tendons involvements in
      Systemic Lupus erythematosus (SLE) patients: A cross-sectional multicenter study.
AB  - OBJECTIVES: The aims of this study in SLE population were (1) to describe
      ultrasonography (US) joint abnormalities, (2) to estimate the reliability of
      clinical swollen joint count (C-SJC) and SLEDAI (C-SLEDAI) versus US-SJC and US
      SLEDAI scores, (3) to highlight specific patterns of lupus patients with Power
      Doppler (PD) abnormalities. METHOD: For this cross-sectional multicenter study,
      151 consecutive adult SLE patients were recruited. Evaluation included a clinical
      standardized joint assessment, B-mode and PD US of 40 joints and 26 tendons
      blinded for clinical examination. Reliability and agreement between clinical and
      B-mode US were calculated using the intraclass correlation coefficients (ICC [95%
      Confidence Interval]). RESULTS: We found a very high frequency of subclinical US
      abnormalities in asymptomatic patients: 85% of patients without joint symptoms
      had at least 1 US abnormality. Among them 46 patients (87%) had a history of
      joint involvement. The most frequent abnormalities were joint effusmaions (108
      patients), synovial hypertrophy (SH, 109 patients) and synovitis (61 patients).
      Joint or tendon PD signal (grade>1) was found in 44% of patients (67/151).
      Synovitis were mainly located especially on MCPs and wrists. Even if reliability
      between clinical and grey-scale US SJC assessments was poor, reliability between
      clinical and US SLEDAI was good. Comparison between SLE patients with and without
      PD signal did not show any specific SLE pattern. CONCLUSION: US may be useful to
      assess joint involvement in SLE patients but did not significantly change SLEDAI
      score.

PMID- 29454671
TI  - Corrigendum to "A vascular endothelial growth factor-dependent sprouting
      angiogenesis assay based on an in vitro human blood vessel model for the study of
      anti-angiogenic drugs" [Ebiomedicine 27 (2018) 225-236].

PMID- 29454672
TI  - Much Ado About Precision.

PMID- 29454673
TI  - Remote Ischemic Preconditioning: A Complex Question with an Even More Complex
      Answer.

PMID- 29454674
TI  - Management of Post-pneumonectomy Bronchopleural Fistula: A Roadmap for Rescue.

PMID- 29454675
TI  - Targeting immune-driven opioid analgesia by sigma-1 receptors: Opening the door
      to novel perspectives for the analgesic use of sigma-1 antagonists.
AB  - Immune cells have a known role in pronociception, since they release a myriad of
      inflammatory algogens which interact with neurons to facilitate pain signaling.
      However, these cells also produce endogenous opioid peptides with analgesic
      potential. The sigma-1 receptor is a ligand-operated chaperone that modulates
      neurotransmission by interacting with multiple protein partners, including the MU
      opioid receptor. We recently found that sigma-1 antagonists are able to induce
      opioid analgesia by enhancing the action of endogenous opioid peptides of immune
      origin during inflammation. This opioid analgesia is seen only at the inflamed
      site, where immune cells naturally accumulate. In this article we review the
      difficulties of targeting the opioid system for selective pain relief, and
      discuss the dual role of immune cells in pain and analgesia. Our discussion
      creates perspectives for possible novel therapeutic uses of sigma-1 antagonists
      as agents able to maximize the analgesic potential of the immune system.

PMID- 29454676
TI  - OPA1: How much do we know to approach therapy?
AB  - OPA1 is a GTPase that controls several functions, such as mitochondrial dynamics
      and energetics, mtDNA maintenance and cristae integrity. In the last years, there
      have been described other cellular pathways and mechanisms involving OPA1
      directly or through its interaction. All this new information, by implementing
      our knowledge on OPA1 is instrumental to elucidating the pathogenic mechanisms of
      OPA1 mutations. Indeed, these are associated with dominant optic atrophy (DOA),
      one of the most common inherited optic neuropathies, and with an increasing
      number of heterogeneous neurodegenerative disorders. In this review, we overview
      all recent findings on OPA1 protein functions, on its dysfunction and related
      clinical phenotypes, focusing on the current therapeutic options and future
      perspectives to treat DOA and the other associated neurological disorders due to
      OPA1 mutations.

PMID- 29454677
TI  - Saturated fatty acids and mortality in patients referred for coronary angiography
      The Ludwigshafen Risk and Cardiovascular Health study.
AB  - BACKGROUND: Saturated fatty acids are thought to be harmful by increasing the
      risk for cardiovascular events. OBJECTIVE: We examined the associations of
      erythrocyte saturated fatty acids with total and cardiovascular mortality in
      patients referred for coronary angiography. METHODS: Red blood cell saturated
      fatty acid (RBC SFA) proportions were measured by gas chromatography at baseline
      in 3259 participants of the Ludwigshafen Risk and Cardiovascular Health study.
      Associations of saturated fatty acid concentrations with mortality were
      investigated using Cox proportional hazards regression. RESULTS: During a median
      follow-up of 9.9 years, 975 patients (29.9%) died and 614 patients (18.8%) died
      of cardiovascular causes. The proportion of palmitic acid (PA, C16:0) ranged from
      15.1% to 27.4% with a mean (standard deviation) of 21.9% (1.15%) and was
      associated with an increased risk for mortality in models adjusted for
      conventional cardiovascular risk factors. An increase of 1-standard deviation in
      PA was associated with a hazard ratio (95% confidence interval) of 1.08 (1.01
      1.16) for all cause and 1.05 (0.96-1.15) for cardiovascular mortality after
      adjustment for cardiovascular risk factors. For the other investigated RBC SFA
      (C14:0, C18:0, C20:0, C22:0, and C24:0), there was no association with mortality
      and also not for the sum of all saturated fatty acids. CONCLUSIONS: Our results
      reveal association with increased mortality risk only for PA but not for the
      other RBC SFAs or the sum of all RBC SFAs and emphasize the need to investigate
      each fatty acid individually rather than studying groups of fatty acids.

PMID- 29454678
TI  - Treatment of coenzyme Q10 for 24 weeks improves lipid and glycemic profile in
      dyslipidemic individuals.
AB  - BACKGROUND: The use of coenzyme Q10 (CoQ10) as an adjuvant treatment with routine
      clinical therapy against metabolic diseases has shown benefit. However, the
      effect of CoQ10 as a primary preventive agent against cardiovascular diseases
      (CVDs) has not been well studied. OBJECTIVE: The objective of this study was to
      investigate the effect of CoQ10 on CVD risk factors in dyslipidemic patients.
      METHODS: In this randomized, double-blinded, placebo-controlled trial, 101
      dyslipidemic subjects without taking any hypoglycemic or hypolipidemic drugs were
      administrated to 120 mg CoQ10 or placebo daily for 24 weeks. Anthropometric
      parameters, lipid and glycemic profile, biomarkers of inflammation, and
      antioxidant capacity were evaluated before and after 12 and 24 weeks of
      intervention. RESULTS: All 101 subjects were included in the analysis. On the
      12th week, compared to placebo, CoQ10 supplementation decreased systolic (P =
      .010) and diastolic pressure (P = .001) and increased serum total antioxidant
      capacity (TAC; P = .003). On the 24th week, compared to placebo, CoQ10
      supplementation further lowered blood pressure and TAC, reduced triglyceride (P =
      .020) and low-density lipoprotein cholesterol (P = .016), and increased ApoA-I (P
      < .001) while decreasing homeostasis model assessment of insulin resistance index
      (P = .009). Adjustment for change of physical activity and energy intake did not
      alter the effect of CoQ10 on the aforementioned parameters but led to significant
      decrease of non-high-density lipoprotein cholesterol in CoQ10 group compared to
      placebo (P = .031). CONCLUSIONS: Twenty-four-week treatment of CoQ10 ameliorates
      multiple CVD risk factors. The versatility and safety of CoQ10 makes it a
      potential candidate for the primary prevention of CVD.

PMID- 29454679
TI  - The prevalence and etiology of extreme hypertriglyceridemia in children: Data
      from a tertiary children's hospital.
AB  - BACKGROUND: Extreme hypertriglyceridemia (eHTG; serum triglycerides >= 2000
      mg/dL) poses a significant risk for acute pancreatitis. There is paucity of data
      regarding the prevalence and etiology of eHTG in children. OBJECTIVE: To
      determine the prevalence, clinical features and etiologies of patients with eHTG
      at a tertiary children's hospital in the United States and in the United States
      National Health and Nutrition Examination Survey (NHANES). METHODS: A
      retrospective analysis was conducted of the electronic medical records of the
      Children's Medical Center, Dallas, from 2000-2015, and the NHANES data from 2005
      2014 for eHTG. RESULTS: Of 30,623 children, 36 (~ 1 in 1000) had eHTG and one
      third of them developed acute pancreatitis. They tended to be female (61%),
      Hispanic (39%), and nonobese (median body mass index z-score 1.60 and 1.25 in
      males and females, respectively). Most patients had secondary causes such as
      uncontrolled diabetes mellitus (30%), L-asparaginase and high-dose corticosteroid
      therapy for acute lymphoblastic leukemia (28%), and sirolimus/tacrolimus therapy
      after solid organ transplantation (14%). Five patients (14%) had type 1
      hyperlipoproteinemia (T1HLP; familial chylomicronemia syndrome). The NHANES data
      revealed that none of the 2362 children had eHTG, and the prevalence in adults
      was 0.02%. CONCLUSIONS: Extreme HTG is rare in children and majority of the
      children had secondary causes. Patients with diabetes mellitus or receiving
      drugs, such as, L-asparaginase, corticosteroids, and sirolimus, should be closely
      monitored for eHTG. Prevalence of T1HLP is approximately 1 in 6000 at a tertiary
      care center with an estimated population prevalence of 1 in 3,00,000. Early
      neonatal screening and intervention for T1HLP can prevent life-threatening
      morbidities such as acute pancreatitis.

PMID- 29454680
TI  - Cardiomyopathy in the pediatric patients.
AB  - Pediatric cardiomyopathies are a group of myocardial diseases with complex
      taxonomies. Cardiomyopathy can occur in children at any age, and it is a common
      cause of heart failure and heart transplantation in children. The incidence of
      pediatric cardiomyopathy is increasing with time. They may be associated with
      variable comorbidities, which are most often arrhythmia, heart failure, and
      sudden death. Medical imaging technologies, including echocardiography, cardiac
      magnetic resonance, and nuclear cardiology, are helpful in reaching a diagnosis
      of cardiomyopathy. Nevertheless, endomyocardial biopsy is the final diagnostic
      method of diagnosis. Patients warrant surgical operations, such as palliative
      operations, bridging operations, ventricular septal maneuvers, and heart
      transplantation, if pharmaceutical therapies are ineffective. Individual
      therapeutic regimens due to pediatric characteristics, genetic factors, and
      pathogenesis may improve the effects of treatment and patients' survival.

PMID- 29454681
TI  - Male Breast Magnetic Resonance Imaging: When is it Helpful? Our Experience Over
      the Last Decade.
AB  - Currently, there are no clear indications or guidelines for performing breast
      magnetic resonance imaging (MRI) in male patients diagnosed with primary breast
      cancer. The literature is also very limited on the usage of breast MRI in male
      patients. Although it is not common or recommended as a routine clinical practice
      to perform breast MRI in male patients even in the setting of a diagnosis of
      breast cancer, there are few instances where MRI may help clinicians and
      surgeons. With a comprehensive review of cases that was performed at our
      institution over the last 10 years, the readers may achieve better understanding
      of when it may be helpful to perform breast MRI in male patients.

PMID- 29454682
TI  - Short communication: Genetic lag represents commercial herd genetic merit more
      accurately than the 4-path selection model.
AB  - Expectation of genetic merit in commercial dairy herds is routinely estimated
      using a 4-path genetic selection model that was derived for a closed population,
      but commercial herds using artificial insemination sires are not closed. The 4
      path model also predicts a higher rate of genetic progress in elite herds that
      provide artificial insemination sires than in commercial herds that use such
      sires, which counters other theoretical assumptions and observations of realized
      genetic responses. The aim of this work is to clarify whether genetic merit in
      commercial herds is more accurately reflected under the assumptions of the 4-path
      genetic response formula or by a genetic lag formula. We demonstrate by tracing
      the transmission of genetic merit from parents to offspring that the rate of
      genetic progress in commercial dairy farms is expected to be the same as that in
      the genetic nucleus. The lag in genetic merit between the nucleus and commercial
      farms is a function of sire and dam generation interval, the rate of genetic
      progress in elite artificial insemination herds, and genetic merit of sires and
      dams. To predict how strategies such as the use of young versus daughter-proven
      sires, culling heifers following genomic testing, or selective use of sexed semen
      will alter genetic merit in commercial herds, genetic merit expectations for
      commercial herds should be modeled using genetic lag expectations.

PMID- 29454683
TI  - Short communication: Heritability of twinning rate in Holstein cattle.
AB  - Multiple births or twinning in cattle is a naturally occurring reproductive
      phenomenon. For dairy cattle, twinning is considered a detrimental trait as it
      can be harmful to cow and calf as well as costly to the producer. The objective
      of this study was to examine recent US calving records for the Holstein breed to
      determine a current estimate of heritability for twinning rate along with effects
      of season and parity. Two models were used in this study: a linear sire model and
      a binary threshold-logit sire model. Both were mixed models considering fixed
      effects and random effects. Analyses were conducted using a restricted maximum
      likelihood method. Heritability estimates were 0.0192 +/- 0.0009 and 0.1420 +/-
      0.0069 for the linear and threshold models, respectively. Repeatabilities from
      the linear and threshold-logit models were 0.0443 +/- 0.0012 and 0.2310 +/-
      0.0072, respectively. The nonzero estimates of heritability indicate the
      potential to select against this trait for genetic improvement of Holstein
      cattle.

PMID- 29454684
TI  - Behavior and productivity of cows milked in automated systems before diagnosis of
      health disorders in early lactation.
AB  - Associations of electronically recorded data were examined before diagnosis of
      health disorders in early-lactation cows in herds with automated milking systems
      (AMS). Rumination time, activity, and milk yield data were collected for 8 mo for
      605 early-lactation cows in 9 commercial AMS herds. Using multivariable
      generalized linear regression models controlling for parity and days in milk,
      data were examined relative to the day of diagnosis for health disorders
      occurring in absence of, or at least 14 d before, another disorder: mastitis (n =
      13), new cases of lameness (n = 45), subclinical ketosis (SCK; n = 113), and
      purulent vaginal discharge (n = 49). All cases of displaced abomasum (DA; n = 8)
      occurred in conjunction with other disorders. Deviations from baseline among
      affected cows were examined, as well as differences compared with a group of
      healthy cows and an average group of all cows, who were given mock diagnosis days
      using the mean days in milk at diagnosis for each disorder. On 6 to 14 d of the 2
      wk before diagnosis, cows with DA or mastitis had lower milk yield, rumination
      time, milking frequency, activity, and milk temperature compared with healthy
      cows as well as deviations from their own baseline rumination time and milk data
      starting 4 to 12 d before diagnosis. Cows with DA had lower AMS supplement intake
      than healthy cows and deviations from their baseline activity and milk
      temperature starting 6 and 4 d before diagnosis, respectively. Cows with mastitis
      had greater milk conductivity than healthy cows and deviated from their baseline
      milking frequency and conductivity 8 and 12 d before diagnosis, respectively.
      Compared with healthy cows, those with SCK or new cases of lameness generally had
      lower milk yield, rumination time, milk temperature, supplement intake, and
      milking and refusal frequencies. Only the milk temperature of lame cows deviated
      from baseline. Thus, acute health disorders (i.e., DA and mastitis) were
      associated with deviations from those cows' baseline AMS data, whereas more
      chronic disorders (i.e., SCK and lameness) were associated with significant but
      subtle longer term changes in milk production and behavior. Because cows with
      health disorders deviated from a group of healthy cows before they deviated from
      their own baseline and from the average of all other cows, including a healthy
      reference group in health alerts could refine the ability of detection models to
      identify subtle deviations in early lactation.

PMID- 29454685
TI  - Genes involved in tolerance to osmotic stress by random mutagenesis in
      Cronobacter malonaticus.
AB  - Cronobacter malonaticus is one of the opportunistic food-borne pathogens in
      powdered infant formula and has unusual abilities to survive under environmental
      stresses such as osmotic conditions. However, the genes involved in osmotic
      stress have received little attention in C. malonaticus. Here, genes involved in
      osmotic stress were determined in C. malonaticus using a transposon mutagenesis
      approach. According to the growth of mutants (n = 215) under 5.0% NaCl
      concentration, the survival of 5 mutants under osmotic stress was significantly
      decreased compared with that of the wild type strain. Five mutating sites,
      including potassium efflux protein KefA, inner membrane protein YqjF,
      peptidylprolyl isomerase, Cys-tRNA(Pro)/Cys-tRNA(Cys) deacylase, and
      oligogalacturonate lyase were successfully identified. In addition, the biofilm
      formation of 5 mutants was determined using crystal violet staining, scanning
      electron microscopy, and confocal laser scanning microscopy, and the biofilms of
      5 mutants significantly decreased within 72 h compared with that of wild type
      strain. This is the first report to determine the genes involved in osmotic
      tolerance in C. malonaticus. The findings provided valuable information for deep
      understanding of the mechanism of survival of C. malonaticus under osmotic
      stress, and a possible relationship between biofilm formation and tolerance to
      osmotic stress was also demonstrated in C. malonaticus.

PMID- 29454686
TI  - Differential effects of a single dose of oral calcium based on postpartum plasma
      calcium concentration in Holstein cows.
AB  - Our objectives were to determine (1) the effect of a single dose of an oral Ca
      bolus within 24 h after parturition on plasma Ca concentration, (2) the response
      of primiparous (PP) and multiparous (MP) cows to this supplementation strategy,
      and (3) differential responses based on plasma Ca at enrollment. For objective 1,
      cows from 1 commercial dairy in New York State were enrolled within 19 h after
      parturition (mean +/- standard deviation = 8.3 +/- 5.3 h) and randomized within
      parity group (first, second, and >=third) to control [CON (n = 25); no placebo]
      or a single dose bolus treatment [BOL (n = 25); 3 oral Ca boluses supplying 54 to
      64 g of Ca]. Plasma Ca was measured repeatedly between 1 and 24 h following
      treatment. For objectives 2 and 3, cows on 6 commercial farms in New York State
      were assigned to treatment as for objective 1 (CON, n = 1,973; BOL, n = 1,976).
      Herd records for health, reproduction, and Dairy Herd Improvement Association
      test day milk production were collected. Mixed effect multivariable models were
      developed using repeated measures ANOVA, Poisson regression, or proportional
      hazard models. Objective 2 analyses considered treatment with periparturient risk
      factors, whereas objective 3 analyses also considered Ca status. No difference
      was observed for plasma Ca between 1 and 24 h after treatment. Primiparous cows
      assigned to BOL calving at >712 d old had decreased risk of one or more health
      disorders [<=30 d in milk; risk ratio (RR) = 0.65, 95% confidence interval (CI) =
      0.51 to 0.84] and those with body condition score >3.5 responded to BOL with
      increased milk production (CON = 31.7 +/- 1.1, BOL = 35.1 +/- 1.1 kg/d), as did
      those with days carried calf >277 (CON = 31.9 +/- 1.0, BOL = 34.7 +/- 1.0 kg/d).
      Reduced risk of one or more health disorders was observed in parity >=3 (RR =
      0.85, 95% CI = 0.81 to 0.89) and MP cows with body condition score >3.5 (retained
      placenta; RR = 0.70, 95% CI = 0.58 to 0.84) or that were lame (displaced
      abomasum; RR = 0.49, 95% CI = 0.32 to 0.75). Differential responses for PP cows
      by Ca status were minimal. For MP cows with low plasma Ca, BOL decreased risk of
      additional Ca treatment (<=1.8 mmol/L; RR = 0.57, 95% CI = 0.40 to 0.80) as well
      as risk of one or more health disorders (<=2.15 mmol/L; RR = 0.90, 95% CI = 0.85
      to 0.95). Supplementation with a single oral dose of Ca could be targeted to
      periparturient risk groups for improved health. Calcium status did not
      differentiate responses of PP cows, but MP cows with low Ca at parturition had
      improved health status when supplemented.

PMID- 29454687
TI  - Bioeconomics of sexed semen utilization in a high-producing Holstein-Friesian
      dairy herd.
AB  - A bioeconomic, stochastic spreadsheet model, that included calculation of the net
      present value of the additional value of all future descendants resulting from
      increased selection intensity, was developed to study the profitability of using
      sexed semen in a high input-high output dairy herd. Three management strategies
      were modeled: (1) only heifers inseminated with sex-sorted semen and cows
      inseminated with unsorted semen; (2) both heifers and cows inseminated with sex
      sorted semen; and (3) a reference scenario, in which all breeding females were
      inseminated with unsorted semen. A Monte Carlo simulation (@risk software,
      Palisade Corp., Ithaca, NY) was run to study the sensitivity of net profit and
      sexed semen advantage to key input parameters. Most input parameters were given
      truncated normal distributions, whereas the maximum numbers of inseminations in
      heifers and cows were given discrete distribution functions. The calculated
      intensity of selection accounted for the different numbers of dairy females born
      for each of the 100,000 iterations. Using sexed semen (X-sorted, female) was
      shown to be profitable, with insemination of both heifers and cows being most
      profitable. The returns on assets were higher when only heifers were inseminated
      with sexed semen (8.54% +/- 2.94; +/-SD) or all females were inseminated with
      sexed semen (8.85% +/- 2.93) than when all females were inseminated with unsexed
      semen (8.38% +/- 2.95). The range in net profit was most sensitive to the assumed
      distributions of milk protein price (?/kg), milk fat price (?/kg), cow pregnancy
      rate, fertilizer price (?/t), and concentrate price (?/t) when unsorted semen was
      used. When only heifers or both heifers and cows were inseminated with sex-sorted
      semen, the range in net profit was most sensitive to the same distributions, with
      fertilizer price and cow pregnancy rate in reverse order of sensitivity. However,
      the range in sex-sorted semen advantage (in net profit) when only heifers were
      inseminated with sex-sorted semen was most sensitive to the assumed distributions
      of cow pregnancy rate, sex-sorted semen pregnancy rate as a percent of unsorted
      semen rates, standard deviation of index, additional cost of sex-sorted semen
      (?/dose), dairy bull calf price (?/head), and dairy heifer calf price (?/head).
      When both heifers and cows were inseminated, the order of importance of the last
      2 inputs was reversed. This study highlights the relatively high effect of
      pregnancy rate and the genetic value of dairy bulls in determining the level of
      financial advantage from using sex-sorted semen in a dairy herd.

PMID- 29454688
TI  - Fermentation and aerobic stability of rehydrated corn grain silage treated with
      different doses of Lactobacillus buchneri or a combination of Lactobacillus
      plantarum and Pediococcus acidilactici.
AB  - We investigated the effects of different types and doses of inoculants for
      ensiling rehydrated corn grain. Shelled corn was finely ground and rehydrated to
      35% moisture. Treatments were as follows: (1) control (no additives); (2)
      Lactobacillus plantarum and Pediococcus acidilactici (LPPA) at a theoretical
      application rate of 1 * 105 cfu/g; (3) LPPA at 5 * 105 cfu/g; (4) LPPA at 1 * 106
      cfu/g; (5) Lactobacillus buchneri (LB) at 1 * 105 cfu/g; (6) LB at 5 * 105 cfu/g;
      and (7) LB at 1 * 106 cfu/g. We detected no effect of inoculant dose. Gas losses
      were greater in silages treated with LB compared with control and LPPA silages.
      Treating silages with LB reduced the concentrations of lactic acid and ethanol
      and increased silage pH and concentrations of acetic acid, propionic acid, and
      1,2-propanediol. At silo opening, silages treated with LB had higher counts of
      lactic acid bacteria but lower yeast counts than the control silage. Aerobic
      stability was greater for silages treated with LB and lower for silages treated
      with LPPA compared with the control. The LB reduced dry matter (DM) losses during
      aerobic exposure, whereas LPPA increased them. Prolamin content was lower in
      silages treated with LB compared with the control, resulting in greater ruminal
      in situ DM degradability. Inoculating LB to a dose of 1 * 105 cfu/g increased
      aerobic stability and ruminal in situ DM degradability of rehydrated corn grain
      silage. The addition of LPPA did not alter the fermentation process and worsened
      the aerobic stability of rehydrated corn grain silage. Further studies are
      warranted to confirm these conclusions in other corn hybrids, inoculants, and
      their combinations.

PMID- 29454689
TI  - Southeast Asia's import demand for skim milk powder: Implications for US
      exporters.
AB  - Dairy industries in Southeast Asia are small and produce less than the domestic
      market demands. As expenditure and population grow in Southeast Asia, it is
      expected that the expenditures on skim milk powder (SMP) will grow. In this
      study, we examined the competitiveness of US SMP in the Southeast Asian market
      with respect to other leading dairy exporters, including the European Union (EU
      28), New Zealand, and Australia. Using monthly data from 2006 to 2015, Rotterdam
      models were used to estimate import demands for SMP in 4 Southeast Asian
      countries. In a scenario using annual averages from 2013 to 2015 as a baseline,
      our findings suggest that a 10% reduction in the US price of SMP would cause
      Indonesia, Singapore, Vietnam, and the Philippines SMP imports from the United
      States to increase by 3.96, 0.44, 2.68, and 1.94 kt, respectively. Under the same
      scenario, the value of US SMP imports would decrease for Indonesia, Vietnam, and
      the Philippines by $4.12, $2.93, and $2.48 million, respectively; however, the
      value of US SMP to Singapore would increase by $0.20 million. Singapore and
      Indonesia expenditures for the US SMP are elastic, which means that as
      expenditure and population in Southeast Asia continue to grow, a 1% increase in
      SMP expenditure in Singapore and Indonesia would result in 1.25 and 1.20%
      increases in US SMP exports.

PMID- 29454690
TI  - Hyperimmune colostrum alleviates rheumatoid arthritis in a collagen-induced
      arthritis murine model.
AB  - Our aging population and the accompanying decline in immune function is a growing
      concern that may be addressed by finding natural methods to enhance the
      immunocompetence of our elderly. Bovine milk and colostrum from cows that have
      been immunized have been shown to provide additional immunoglobulins and other
      bioactive molecules that enhance immune function. The purpose of this study was
      to investigate the ability of hyperimmune bovine colostrum to alleviate the
      symptoms of rheumatoid arthritis in a murine model. The collagen-induced
      arthritis DBA/1J murine model was used for this study. Mice were fed colostrum
      from immunized cows at either 5 or 10 mg/mouse per day or controls for 49 d. The
      data showed that the colostrum-fed groups had significantly lower total swelling
      scores and significantly lower collagen-specific antibody (IgG2a), inflammation
      associated antibody (total IgG), and the inflammatory cytokines tumor necrosis
      factor alpha, IL-2, IL-6, and IFN-gamma. The results strongly suggest that
      colostrum from immunized cows may have anti-inflammatory activity in a mouse
      model of rheumatoid arthritis.

PMID- 29454691
TI  - The effect of alfalfa (Medicago sativa) silage chop length and inclusion rate
      within a total mixed ration on the ability of lactating dairy cows to cope with a
      short-term feed withholding and refeeding challenge.
AB  - The objectives of the study were (1) to test whether 6 h of feed deprivation
      followed by refeeding induces an acidosis challenge in dairy cattle and (2) to
      quantify the acidosis challenge mitigation potential of increased alfalfa silage
      concentration in the diet. Alfalfa silage constituted either 25 or 75% of forage
      dry matter (DM) replacing corn silage [low (LA) or high alfalfa (HA)] and was
      chopped to either 14 or 19 mm theoretical length [short (S) or long (L)]. Dietary
      treatments LAS, LAL, HAS, or HAL were offered to 4 rumen-cannulated Holstein
      dairy cattle (161 d in milk; 5th or 6th parity) in a 4 * 4 Latin square design
      study with 21-d periods. Starch concentration was 69 g/kg of DM higher for LA
      diets than HA diets. Feed was withheld for 6 h followed by ad libitum refeeding
      on d 18 of each period. Measurements of DM intake, milk yield and composition,
      rumen pH, and eating and rumination behavior were taken on 1 baseline day, the
      challenge day, and 2 further recovery days. After refeeding, rumen pH was reduced
      in cows fed LA diets but not HA diets. Feeding LAL resulted in the greatest
      subclinical acidosis risk (pH <5.8 for 355 min on the first recovery day).
      Animals fed LA produced 4.4 L less milk on the challenge day in comparison to
      baseline. It was concluded that short-term feed deprivation detrimentally
      affected rumen health and milk yield in dairy cattle normally fed ad libitum, but
      had no effect on DM intake or milk composition. Feeding alfalfa silage in place
      of corn silage mitigated acidosis risk due to interrupted feed supply, likely due
      to a combination of lower starch concentration in HA diets, greater effective
      fiber concentration, and higher buffering capacity of alfalfa relative to corn
      silage.

PMID- 29454692
TI  - From milk to cheese: Evolution of flavor fingerprint of milk, cream, curd, whey,
      ricotta, scotta, and ripened cheese obtained during summer Alpine pasture.
AB  - The role of each step of cheese and ricotta making in development of flavor of
      cheese and other dairy products is not yet well known. The objectives of this
      study were to characterize volatile organic compounds (VOC) in cheese and ricotta
      making with bulk milk from cows grazing in a highland area and to evaluate their
      evolution in the various dairy products and by-products obtained during the
      production processes. A group of 148 cows was grazed day and night on pasture
      from June to September. A total of 7 cheese-making sessions were carried out
      using the bulk milk collected every 2 wk during summer pasturing according to the
      artisanal procedure used for Malga cheese production. All milks, products, and by
      products were sampled, and the VOC content of milk, cream, whey, ricotta, scotta
      (residual liquid), fresh cheeses, and cheeses ripened for 6 and 12 mo was
      determined by solid-phase microextraction gas chromatography-mass spectrometry.
      Forty-nine compounds were identified belonging to the following chemical
      families: alcohols (13), aldehydes (9), esters (8), free fatty acids (6), ketones
      (5), lactones (2), sulfurs (2), terpenes (2), phenol (1), and benzene (1). The
      results showed that the amounts of VOC in the various dairy products differed
      significantly. Comparisons between the VOC of 4 types of milk (whole evening,
      skim evening, whole morning, mixed in the vat) showed that the skimming process
      had the greatest effect, with about half of all the VOC analyzed affected,
      followed by time of milking (evening milking vs. morning milking) and mixing
      (skim evening milk mixed with whole morning milk). In general, among fresh
      products, cream had higher contents of fatty acids, sulfurs, and terpene volatile
      compounds than fresh cheese and ricotta, whereas ricotta showed a very high VOC
      amount compared with fresh cheese, probably due to its high processing
      temperature. The effects of the progressive nutrient depletion in milk during
      processing were investigated by comparing the amounts of VOC in vat milk, whey,
      and scotta. Although milk contained greater amounts of nutrients, whey and
      especially scotta had higher concentrations of VOC, with the exception of esters,
      sulfurs, terpenes, and phenolic compounds, as a result of physicochemical and
      microbial modifications during processing. Finally, the effect of ripening was
      tested by comparing the VOC of fresh and ripened cheeses (6 and 12 mo), revealing
      that VOC release increased dramatically during the first semester and further
      with increasing the ripening period to 1 yr. In particular, some alcohols (butan
      2-ol), aldehydes (2-methylpropanal, hexanal, and heptanal), esters (ethyl
      butanoate and ethyl hexanoate), fatty acids (acetic, butanoic, and hexanoic
      acids), and ketones (butan-2-one, pentan-2-one, and heptan-2-one) showed a very
      large increase. In conclusion, according to the artisanal milk processing carried
      out for Malga cheese production, the quantity of VOC was shown to increase about
      3 times during cheese making (from milk in vat to fresh cheese plus whey), almost
      4 times during ricotta making (from whey to ricotta plus scotta), and about 16
      times during 1 yr of ripening of cheese.

PMID- 29454693
TI  - Mating strategies to maximize genetic merit in dairy cattle herds.
AB  - The genetic merit of a herd is a key determinant in productivity for dairy
      farmers. However, making breeding decisions to maximize the rate of genetic gain
      can be complex because there is no certainty about which cows will become
      pregnant with a heifer calf. In this study, breeding worth (BrW) was used as a
      measure of genetic merit, and several mating strategies were evaluated. These
      strategies included randomly mating whole herds to the entire bull team,
      excluding low-ranked cows from producing replacement heifers, and nominating high
      ranked cows to the most highly ranked bulls. Simulations were undertaken using 4
      bull teams generated from bulls currently marketed in New Zealand and a selection
      of New Zealand dairy herds. Average replacement heifer BrW was calculated for
      1,000 iterations of each combination of mating strategy, herd, and bull team
      (scenario). Variation in resulting average replacement heifer BrW within
      scenarios was due to random sampling of which cows became pregnant with a heifer
      calf. Relative to mating the whole herd to an entire bull team, excluding the
      lowest ranked cows from producing replacements resulted in the greatest increase
      in average replacement heifer BrW across all herds and bull teams, with a gain of
      approximately 0.4 BrW point for each 1% of cows excluded. Nominating top-ranking
      cows to the highest ranking bulls in the team had little effect (0.06-0.13 BrW
      increase for each 1% of top cows nominated) in improving BrW of replacement
      heifers. The number of top bulls nominated had a variable effect depending on the
      BrW spread of the entire bull team. Although excluding cows with the lowest BrW
      from producing replacement heifers is most effective for improving BrW, it is
      important to ensure that the number of heifers born is sufficient to replace cows
      leaving the herd. It is likely that optimal strategies for improving BrW will
      vary from farm to farm depending not only on the BrW structure of the herd, the
      bull team available, and the reproduction success on farm but also on farm
      management practices. This simulation study provides expected outcomes from a
      variety of mating strategies to allow informed decision making on farm.

PMID- 29454694
TI  - Milk losses associated with somatic cell counts by parity and stage of lactation.
AB  - The reduction of milk production caused by subclinical mastitis in dairy cows was
      evaluated through the regression of test-day milk yield on log-transformed
      somatic cell counts (LnSCC). Official test-day records (n = 1,688,054) of
      Holstein cows (n = 87,695) were obtained from 719 herds from January 2010 to
      December 2015. Editing was performed to ensure both reliability and consistency
      for the statistical analysis, and the final data set comprised 232,937 test-day
      records from 31,692 Holstein cows in 243 herds. A segmented regression was fitted
      to estimate the cutoff point in the LnSCC scale where milk yield started to be
      affected by mastitis. The statistical model used to explain daily milk yield
      included the effect of herd as a random effect and days in milk and LnSCC as
      fixed effects regressions, and analyses were performed by parity and stage of
      lactation. The cutoff point where milk yield starts to be affected by changes in
      LnSCC was estimated to be around 2.52 (the average of all estimates of
      approximately 12,400 cells/mL) for Holsteins cows from Brazilian herds. For first
      lactation cows, milk losses per unit increase of LnSCC had estimates around 0.68
      kg/d in the beginning of the lactation [5 to 19 d in milk (DIM)], 0.55 kg/d in
      mid-lactation (110 to 124 DIM), and 0.97 kg/d at the end of the lactation (289 to
      304 DIM). For second-lactation cows, milk losses per unit increase of LnSCC had
      estimates around 1.47 kg/d in the beginning of the lactation (5 to 19 DIM), 1.09
      kg/d in mid-lactation (110 to 124 DIM), and 2.45 kg/d at the end of the lactation
      (289 to 304 DIM). For third-lactation cows, milk losses per unit increase of
      LnSCC had estimates around 2.22 kg/d in the beginning of the lactation (5 to 19
      DIM), 1.13 kg/d in mid-lactation (140 to 154 DIM), and 2.65 kg/d at the end of
      the lactation (289 to 304 DIM). Daily milk losses caused by increased LnSCC were
      dependent on parity and stage of lactation, and these factors should be
      considered when estimating losses associated with subclinical mastitis.

PMID- 29454695
TI  - Short communication: Cholesterol oxidation products in traditional buttermilk.
AB  - The aim of this study was to quantitatively and qualitatively assess the content
      of cholesterol oxidation products in traditional buttermilk after butter
      production. Cholesterol oxidation products (COP) exhibit a wide spectrum of
      biological activity, including cytotoxic, carcinogenic, and pro-oxidative
      properties. Buttermilk has about 2 mg of COP/kg of fat, including 7beta
      hydroxycholesterol and 5,6alpha-epoxycholesterol. Buttermilk immediately after
      production had a relatively high level of 7beta-hydroxycholesterol (1.47 mg/kg),
      which decreased to 0.61 mg/kg after storage for 10 h at 3 degrees C. During
      storage, the content of 5,6alpha-epoxycholesterol increased from 0.50 to 1.40
      mg/kg. After 10 h of storage, the antioxidant potential of the buttermilk
      decreased (expressed as radical scavenging ability; change in 1,1-diphenyl-2
      picrylhydrazyl = 32.2%). This study showed the presence of COP in fresh and
      stored buttermilk and the influence of time on changing the direction of
      cholesterol oxidation.

PMID- 29454696
TI  - The effect of tube versus bottle feeding colostrum on immunoglobulin G
      absorption, abomasal emptying, and plasma hormone concentrations in newborn
      calves.
AB  - The objective of this study was to determine if feeding colostrum to newborn
      calves through an esophageal tube, compared with a nipple bottle, would delay
      abomasal emptying, which would in turn decrease passive transfer of IgG and
      plasma glucose, insulin, and glucagon-like peptide (GLP) 1 and GLP-2
      concentrations. Twenty newborn Holstein bull calves were fed 3 L of colostrum
      replacer (200 g of IgG) through either an esophageal tube or nipple bottle at 2 h
      after birth followed by feeding pooled whole milk every 12 h after birth.
      Acetaminophen was mixed into the colostrum meal as a marker for abomasal
      emptying. A jugular catheter was inserted 1 h after birth and blood was sampled
      frequently to analyze serum for IgG and acetaminophen and plasma for glucose,
      insulin, GLP-1, and GLP-2. Feeding method did not affect abomasal emptying, and
      as a result no treatment effect was present on serum IgG concentrations. Maximum
      concentration of serum IgG was 24.4 +/- 0.40 mg/mL (+/- standard error), which
      was reached at 14.6 +/- 1.88 h after the colostrum meal for both groups. Apparent
      efficiency of absorption at maximum concentration of IgG was 52.9%, indicating
      high efficiency of passive transfer of IgG for both treatments. Tube feeding
      increased glucose and insulin area under the curve before the first milk meal,
      most likely due to the decreased time to consume the colostrum meal. In addition,
      tube-fed calves consumed 0.5 +/- 0.13 L more milk in their first milk meal than
      bottle-fed calves. No treatment effect on plasma concentrations of GLP-1 or GLP-2
      was present, but both hormones increased after colostrum feeding. These findings
      confirm that there is no effect on absorption of IgG from colostrum when feeding
      good-quality colostrum at a volume of 3 L through either an esophageal tube or
      nipple bottle.

PMID- 29454697
TI  - Symposium review: Building a better cow-The Australian experience and future
      perspectives.
AB  - Genomic selection has led to opportunities for developing new breeding values
      that rely on phenotypes in dedicated reference populations of genotyped cows. In
      Australia, it has been applied to 2 novel traits: feed efficiency, which was
      released in 2015 as feed saved breeding values, and heat tolerance genomic
      breeding values, released for the first time in 2017. Feed saved is already
      included in the national breeding objective, which is focused on profitability
      and designed to be in line with farmer preferences. Our future focus is on traits
      associated with animal health, either directly or in combination with predictor
      traits, such as mid-infrared spectral data and, into the future, automated data
      capture. Although it is common for many evaluated traits to have genomic
      reliabilities ranging between 60 and 75%, many new, genomic information-only
      traits are likely to have reliabilities of less than 50%. Pooling of phenotype
      data internationally and investing in maintenance of reference populations is one
      option to increase the reliability of these traits; the other is to apply
      improved genomic prediction methods. For example, advances in the use of sequence
      data, in addition to gene expression studies, can lead to improved persistence of
      genomic breeding values across breeds and generations and potentially lead to
      greater reliabilities. Lower genomic reliabilities of novel traits could reduce
      the overall index reliability. However, provided these traits contribute to the
      overall breeding objective (e.g., profit), they are worth including. Bull
      selection tools and personalized genetic trends are already available, but
      increased access to economic and automatic capture farm data may see even better
      use of data to improve farm management and selection decisions.

PMID- 29454698
TI  - Udder health of dairy cows fed different dietary energy levels after a short or
      no dry period without use of dry cow antibiotics.
AB  - Reports on the effects of length of dry period (DP) on udder health of cows that
      were not treated with dry cow antibiotics are scarce. Additionally, the effects
      of a reduced dietary energy level for cows with a 0-d DP on udder health have not
      yet been studied. The aims of this study were (1) to compare effects of a 0-d or
      30-d DP without use of dry cow antibiotics on udder health across the DP and
      subsequent lactation in dairy cows fed different dietary energy levels and (2) to
      evaluate associations between udder health and metabolic status of dairy cows.
      Five weeks before the expected calving date, Holstein-Friesian dairy cows (n =
      115) were blocked for parity, expected calving date, and milk yield and somatic
      cell count (SCC) at their 2 last test days and were randomly assigned to 2 DP
      lengths: 0-d DP (n = 77) or 30-d DP (n = 38). Quarter milk samples were taken in
      wk 5 prepartum and in wk 1 and 5 postpartum. Proportion of quarters with elevated
      SCC (SCC >=200,000 cells/mL) and proportion of udder pathogens in quarter milk
      samples did not differ between DP lengths among weeks. After calving, 102 of
      these cows were randomly assigned to 3 treatments: a 30-d DP with a standard
      energy level required for expected milk yield (30-d DP SEL; n = 36), a 0-d DP
      with the same energy level as cows with a 30-d DP (0-d DP SEL; n = 33), and a 0-d
      DP with a low energy level (0-d DP LEL, n = 33). From wk 8 of lactation onward,
      cows received either a glucogenic ration consisting of corn silage and grass
      silage or a lipogenic ration consisting of grass silage and sugar beet pulp at a
      standard or low energy level. During wk 1 to 7 postpartum, treatment did not
      affect SCC or SCC corrected for milk yield. During wk 8 to 44 of lactation, 0-d
      DP SEL cows had a greater SCC than 0-d DP LEL or 30-d DP SEL cows and had a
      greater SCC corrected for milk yield than 0-d DP LEL cows. During wk 1 to 44 of
      lactation, occurrence of at least 1 elevation of SCC (SCC >=200,000 cells/mL
      after 2 wk of SCC <200,000 cells/mL) was not different among treatments. The 0-d
      DP SEL cows but not the 0-d DP LEL cows tended to have a 2.17 times greater
      hazard of having a case of clinical mastitis at any time in lactation than 30-d
      DP SEL cows. In wk 1 to 44 of lactation, lower fat- and protein- corrected milk
      yield and energy intake, greater energy balance, and greater plasma insulin
      concentration were associated with greater SCC. In conclusion, DP length did not
      affect udder health in the DP and in early lactation but seemed to decrease udder
      health for 0-d DP SEL cows in later lactation compared with 30-d DP SEL or 0-d DP
      LEL cows.

PMID- 29454699
TI  - Interrelations between the rumen microbiota and production, behavioral, rumen
      fermentation, metabolic, and immunological attributes of dairy cows.
AB  - Different studies have shown a strong correlation between the rumen microbiome
      and a range of production traits (e.g., feed efficiency, milk yield and
      components) in dairy cows. Underlying dynamics concerning cause and effect are,
      however, still widely unknown and warrant further investigation. The aim of the
      current study was to describe possible functional interrelations and pathways
      using a large set of variables describing the production, the metabolic and
      immunological state, as well as the rumen microbiome and fermentation
      characteristics of dairy cows in early lactation (n = 36, 56 +/- 3 d in milk). It
      was further hypothesized that the feed intake-associated behavior may influence
      the ruminal fermentation pattern, and a set of variables describing these
      individual animal attributes was included. Principal component analysis as well
      as Spearman's rank correlations were conducted including a total of 265
      variables. The attained plots describe several well-known associations between
      metabolic, immunological, and production traits. Main drivers of variance within
      the data set included milk production and efficiency as well as rumen
      fermentation and microbiome diversity attributes, whereas behavioral, metabolic,
      and immunological variables did not exhibit any strong interrelations with the
      other variables. The previously well-documented strong correlation of production
      traits with distinct prokaryote groups was confirmed. This mainly included a
      negative correlation of operational taxonomic units ascribed to the Prevotella
      genus with milk and fat yield and feed efficiency. A central role of the animals'
      feed intake behavior in this context could not be affirmed. Furthermore,
      different methodological and interpretability aspects concerning the microbiome
      analysis by 16S rRNA gene sequencing, such as the discrepancy between taxonomic
      classification and functional communality, as well as the comparability with
      other studies, are discussed. We concluded that, to further investigate the
      driving force that causes the difference between efficient and inefficient
      animals, studies including more sophisticated methods to describe phenotypical
      traits of the host (e.g., rumen physiology, metabolic and genetic aspects) as
      well as the rumen microbiome (e.g., metagenome, metatranscriptome, metaproteome,
      and metabolome analysis) are needed.

PMID- 29454700
TI  - Technical note: An in vivo method to determine kinetics of unsaturated fatty acid
      biohydrogenation in the rumen.
AB  - Rumen microbial biohydrogenation (BH) of unsaturated fatty acids (UFA) has been
      extensively studied in vitro; however, in vitro BH pathways, rates, and extents
      may not parallel those in vivo. The objective was to develop an assay to assess
      in vivo rates, pathways, and extent of BH of oleic (OA), linoleic (LA), and alpha
      linolenic (ALA) acids. Each UFA was characterized in a separate experiment, each
      using 4 ruminally cannulated lactating Holstein cows. A single bolus consisting
      of 200 g of a UFA-oil [experiment 1 (EXP1): 87% OA sunflower, experiment 2
      (EXP2): 70% LA safflower, and experiment 3 (EXP3): 54% ALA flaxseed] and 12 g of
      heptadecanoic acid (C17:0) was mixed into the rumen through the fistula. Rumen
      digesta was collected at -1, -0.25, 0.1, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, and 6
      h relative to the bolus. Overall, the triglyceride boluses increased total fatty
      acids (FA) in the rumen from 3.9 (standard deviation = +/-1.4) to 7.3% (+/-1.4)
      of rumen dry matter and enriched C17:0 from 0.4 (+/-0.1) to 2.5% (+/-0.5) of FA.
      The bolus enriched OA from 8.9 (+/-1.0) to 30.1% (+/-4.6) of FA in EXP1, LA from
      11.1 (+/-1.8) to 35.9% (+/-5.0) of FA in EXP2, and ALA from 2.1 (+/-0.1) to 19.8%
      (+/-4.3) of FA in EXP3. The disappearances of C17:0, OA, LA, and ALA were fit to
      a single exponential decay model. The first-order rate of C17:0 rumen
      disappearance (turnover) was 9.1, 6.9, and 5.2%/h in EXP1, EXP2, and EXP3,
      respectively, and was used as a marker of FA passage. The rate of total rumen
      turnover of OA was 54.1%/h, LA was 60.5%/h, and ALA was 93.0%/h in EXP1, EXP2,
      and EXP3, respectively. Rumen concentration of all 3 UFA reached prebolus
      concentrations within 4 h. The calculated extent of lipolysis and initial
      isomerization was 85.6% for OA, 89.8% for LA, and 94.7% for ALA in EXP1, EXP2,
      and EXP3, respectively. Assuming that BH equals total disappearance minus
      passage, the rates of lipolysis and initial isomerization were 45.0, 53.6, and
      87.8%/h for OA, LA, and ALA in EXP1, EXP2, and EXP3, respectively. Analysis of
      the data using compartmental modeling showed that the normal BH pathways proposed
      in the literature explained 46.0, 37.3, and 49.8% of the BH of OA, LA, and ALA in
      EXP1, EXP2, and EXP3, respectively. Based on the model, BH of trans C18:1 FA was
      the rate-limiting step to complete BH. Importantly, oils were provided as
      triglycerides and the reported rates represent the rate of lipolysis and BH. In
      conclusion, the rate of ruminal BH of OA, LA, and ALA was higher than that
      commonly observed in vitro, but the extent of BH was near expected values. The
      method developed provides a potential in vivo assay of ruminal BH for use in
      future experiments and modeling efforts.

PMID- 29454701
TI  - Fatty acid elongase 5 (ELOVL5) alters the synthesis of long-chain unsaturated
      fatty acids in goat mammary epithelial cells.
AB  - Increased production of long-chain unsaturated fatty acids (LCUFA) can have a
      positive effect on the nutritional value of ruminant milk for human consumption.
      In nonruminant species, fatty acid elongase 5 (ELOVL5) is a key enzyme for
      endogenous synthesis of long-chain unsaturated fatty acids. However, whether
      ELOVL5 protein plays a role (if any) in ruminant mammary tissue remains unclear.
      In the present study, we assessed the mRNA abundance of ELOVL5 at 3 stages of
      lactation in goat mammary tissue. Results revealed that ELOVL5 had the lowest
      expression at peak lactation compared with the nonlactating and late-lactating
      periods. The ELOVL5 was overexpressed or knocked down to assess its role in goat
      mammary epithelial cells. Results revealed that ELOVL5 overexpression increased
      the expression of perilipin2 (PLIN2) and decreased diacylglycerolacyltransferase
      2 (DGAT2) and fatty acid desaturase 2 (FADS2) mRNA, but had no effect on the
      expression of DGAT1, FADS1, and stearoyl-CoA desaturase 1 (SCD1). Overexpression
      of ELOVL5 decreased the concentration of C16:1n-7, whereas no significant change
      in C18:1n-7 and C18:1n-9 was observed. Knockdown of ELOVL5 decreased the
      expression of PLIN2 but had no effect on DGAT1, DGAT2, FADS1, FADS2, and SCD1
      mRNA expression. Knockdown of ELOVL5 increased the concentration of C16:1n-7 and
      decreased that of C18:1n-7. The alterations of expression of genes related to
      lipid metabolism after overexpression or knockdown of ELOVL5 suggested a negative
      feedback regulation by the products of ELOVL5 activation. However, the content of
      triacylglycerol was not altered by knockdown or overexpression of ELOVL5 in goat
      mammary epithelial cells, which might have been due to the insufficient
      availability of substrate in vitro. Collectively, these are the first in vitro
      results highlighting an important role of ELOVL5 in the elongation of 16-carbon
      to 18-carbon unsaturated fatty acids in ruminant mammary cells.

PMID- 29454702
TI  - C-C motif chemokine ligand 2 induces proliferation and prevents
      lipopolysaccharide-induced inflammatory responses in bovine mammary epithelial
      cells.
AB  - C-C motif chemokine ligand 2 (CCL2) is a small chemokine which belongs to the CC
      type chemokine family, and has chemoattractant activity for recruitment of
      monocytes to sites of inflammation. Overexpressed CCL2 binding to its receptor C
      C chemokine receptor 2 increases the risk of breast cancer in humans, but its
      effects on proliferation of bovine mammary epithelial cells is not known.
      Maintaining a high level of proliferative activity in bovine mammary epithelial
      cells during lactation is important for improving milk yield and can benefit the
      dairy industry economically. In the present study, we demonstrated that CCL2
      induces proliferation of MAC-T cells, a bovine mammary epithelial cell line, and
      stimulates progression of the cell cycle through stimulation of expression of
      cyclin D1. Moreover, CCL2 activates phosphoinositide 3-kinase (PI3K)/AKT [AKT,
      P70-S6 kinase 1 (P70S6K), ribosomal protein S6 (S6)] and mitogen activated
      protein kinase (MAPK) [extracellular signal-regulated kinase-1/2 (ERK1/2), c-Jun
      N-terminal kinase (JNK), and P38] pathways, which are involved in proliferation
      of MAC-T cells, as evidenced by co-treatment of MAC-T cells with pharmacological
      inhibitors of cell signaling transcription factors including Wortmannin, U0126,
      and SP600125. The CCL2 in MAC-T cells attenuates endoplasmic reticulum stress
      induced by tunicamycin, suggesting that CCL2 regulates intracellular synthesis of
      proteins and lipids and prevents activation of apoptotic pathways initiated in
      response to endoplasmic reticulum stress. Furthermore, CCL2 is involved in
      alleviating lipopolysaccharide (LPS)-induced inflammatory responses in MAC-T
      cells by reducing LPS-induced expression of IL8, IL6, and nuclear factor kappa B
      subunit 1 (NFKB1). Collectively, CCL2 is a novel target for improving the
      quantity and quality of milk from cows through stimulation of proliferation on
      mammary epithelial cells and attenuation of LPS-induced inflammatory responses.

PMID- 29454703
TI  - Synthesis and evaluation of novel dolastatin 10 derivatives for versatile
      conjugations.
AB  - Dolastatin 10 (1) is a highly potent cytotoxic microtubule inhibitor
      (cytotoxicity IC50 < 5.0 nM) and several of its analogs have recently been used
      as payloads in antibody drug conjugates. Herein, we describe the design and
      synthesis of a series of novel dolastatin 10 analogs useful as payloads for
      conjugated drugs. We explored analogs containing functional groups at the
      thiazole moiety at the C-terminal of dolastatin 10. The functional groups
      included amines, alcohols, and thiols, which are representative structures used
      in known conjugated drugs. These novel analogs showed excellent potency in a
      tumor cell proliferation assay, and thus this series of dolastatin 10 analogs is
      suitable as versatile payloads in conjugated drugs. Insights into the structure
      activity relationships of the analogs are also discussed.

PMID- 29454704
TI  - Selective inhibition of CYP2C8 by fisetin and its methylated metabolite,
      geraldol, in human liver microsomes.
AB  - Fisetin is a flavonol compound commonly found in edible vegetables and fruits. It
      has anti-tumor, antioxidant, and anti-inflammatory effects. Geraldol, the O
      methyl metabolite of fisetin in mice, is reported to suppress endothelial cell
      migration and proliferation. Although the in vivo and in vitro effects of fisetin
      and its metabolites are frequently reported, studies on herb-drug interactions
      have not yet been performed. This study was designed to investigate the
      inhibitory effect of fisetin and geraldol on eight isoforms of human cytochrome
      P450 (CYP) by using cocktail assay and LC-MS/MS analysis. The selective
      inhibition of CYP2C8-catalyzed paclitaxel hydroxylation by fisetin and geraldol
      were confirmed in pooled human liver microsomes (HLMs). In addition, an IC50
      shift assay under different pre-incubation conditions confirmed that fisetin and
      geraldol shows a reversible concentration-dependent, but not mechanism-based,
      inhibition of CYP2C8. Moreover, Michaelis-Menten, Lineweaver-burk plots, Dixon
      and Eadie-Hofstee showed a non-competitive inhibition mode with an equilibrium
      dissociation constant of 4.1 MUM for fisetin and 11.5 MUM for geraldol,
      determined from secondary plot of the Lineweaver-Burk plot. In conclusion, our
      results indicate that fisetin showed selective reversible and non-competitive
      inhibition of CYP2C8 more than its main metabolite, geraldol, in HLMs.

PMID- 29454705
TI  - Schwann cell precursor: a neural crest cell in disguise?
AB  - Schwann cell precursors (SCPs) are multipotent embryonic progenitors covering all
      developing peripheral nerves. These nerves grow and navigate with unprecedented
      precision, delivering SCP progenitors to almost all locations in the embryonic
      body. Within specific developing tissues, SCPs detach from nerves and generate
      neuroendocrine cells, autonomic neurons, mature Schwann cells, melanocytes and
      other cell types. These properties of SCPs evoke resemblances between them and
      their parental population, namely, neural crest cells. Neural crest cells are
      incredibly multipotent migratory cells that revolutionized the course of
      evolution in the lineage of early chordate animals. Given this similarity and
      recent data, it is possible to hypothesize that proto-neural crest cells are
      similar to SCPs spreading along the nerves. Here, we review the multipotency of
      SCPs, the signals that govern them, their potential therapeutic value, SCP's
      embryonic origin and their evolutionary connections. We dedicate this article to
      the memory of Wilhelm His, the father of the microtome and "Zwischenstrang",
      currently known as the neural crest.

PMID- 29454707
TI  - Crystal Structure of the Capsid Protein from Zika Virus.
AB  - Recently, Zika virus (ZIKV) emerged as a global public health concern and is
      distinct from other flaviviruses in many aspects, for example, causing
      transplacental infection, fetal abnormalities and vector-independent transmission
      through body fluids in humans. The capsid (C) protein is a multifunctional
      protein, since it binds to viral RNA in the process of nucleocapsid assembly and
      plays important roles in virus infection processes by interacting with cellular
      proteins, modulating cellular metabolism, apoptosis and immune response. Here we
      solved the crystal structure of ZIKV C protein at a resolution of 1.9A. The ZIKV
      C protein structure contains four alpha helices with a long pre-alpha1 loop and
      forms dimers. The unique long pre-alpha1 loop in ZIKV C contributes to the
      tighter association of dimeric assembly and renders a divergent hydrophobic
      feature at the lipid bilayer interface in comparison with the known C structures
      of West Nile and dengue viruses. We reported the interaction between the ZIKV C
      protein and lipid droplets through confocal microscopy analysis. Substitutions of
      key amino acids in the pre-alpha1 loop of ZIKV C disrupted the interaction with
      lipid droplets, indicating that the loop is critical for membrane association. We
      also recognized that ZIKV C protein possesses broad binding capability to
      different nucleotide types, including single-stranded and double-stranded RNAs or
      DNAs. Furthermore, the highly positively charged interface, mainly formed by
      alpha4 helix, is proposed to be responsible for nucleotide binding. These
      findings will greatly enhance our understanding of ZIKV C protein, providing
      information for anti-ZIKV drug design targeting the C protein.

PMID- 29454706
TI  - GATA6 phosphorylation by Erk1/2 propels exit from pluripotency and commitment to
      primitive endoderm.
AB  - The transcription factor GATA6 and the Fgf/Ras/MAPK signaling pathway are
      essential for the development of the primitive endoderm (PrE), one of the two
      lineages derived from the pluripotent inner cell mass (ICM) of mammalian
      blastocysts. A mutant mouse line in which Gata6-coding exons are replaced with
      H2BGFP (histone H2B Green Fluorescence Protein fusion protein) was developed to
      monitor Gata6 promoter activity. In the Gata6-H2BGFP heterozygous blastocysts,
      the ICM cells that initially had uniform GFP fluorescence signal at E3.5 diverged
      into two populations by the 64-cell stage, either as the GFP-high PrE or the GFP
      low epiblasts (Epi). However in the GATA6-null blastocysts, the originally
      moderate GFP expression subsided in all ICM cells, indicating that the GATA6
      protein is required to maintain its own promoter activity during PrE linage
      commitment. In embryonic stem cells, expressed GATA6 was shown to bind and
      activate the Gata6 promoter in PrE differentiation. Mutations of a conserved
      serine residue (S264) for Erk1/2 phosphorylation in GATA6 protein drastically
      impacted its ability to activate its own promoter. We conclude that
      phosphorylation of GATA6 by Erk1/2 compels exit from pluripotent state, and the
      phosphorylation propels a GATA6 positive feedback regulatory circuit to compel
      PrE differentiation. Our findings resolve the longstanding question on the dual
      requirements of GATA6 and Ras/MAPK pathway for PrE commitment of the pluripotent
      ICM.

PMID- 29454708
TI  - Incidence and Risk of Oxaliplatin-Induced Hypersensitivity in Patients with
      Asymptomatic Prior Exposure: A Prospective Observational Study.
AB  - BACKGROUND: Oxaliplatin-related hypersensitivity reactions (HSRs), which can be
      life threatening, have introduced a dilemma regarding the use of chemotherapeutic
      agents. Because repeated exposure to oxaliplatin may increase the risk of
      sensitization, patients with a history of prior asymptomatic exposure require
      risk-stratified care. OBJECTIVE: This study aimed to elucidate the incidence and
      risk of oxaliplatin HSRs in patients with a history of asymptomatic prior
      exposure. METHODS: We performed a prospective observational study of patients who
      completed oxaliplatin-based chemotherapy between March 2013 and January 2015.
      Prior exposure to oxaliplatin, the oxaliplatin-free interval, reaction severity,
      eosinophil counts, and premedication were reviewed to assess the risk factors.
      RESULTS: A total of 793 patients were enrolled, among whom 148 (18.7%)
      experienced an HSR. The HSR incidence was 15.2% among oxaliplatin-naive patients
      but increased to 31.9% among those with a history of asymptomatic exposure and
      75.0% among those with a history of oxaliplatin HSRs during the previous
      exposure, despite prophylaxis. The mean HSR onset cycle was earliest in the
      previous HSR group, followed by the previous asymptomatic exposure and
      nonexposure groups. The HSR severity also differed according to the previous
      exposure history and HSRs. In the multivariate analysis, prior exposure to
      oxaliplatin (odds ratio [OR], 3.78; 95% confidence interval [CI], 2.46-5.79) and
      a longer oxaliplatin-free interval (>=36 months; OR, 4.85; 95% CI, 1.60-14.37)
      were independent risk factors for HSRs. CONCLUSIONS: Previous exposure to
      oxaliplatin is a risk factor for earlier HSR onset and more severe and frequent
      HSR episodes, even if prior therapy was well tolerated.

PMID- 29454709
TI  - In Vitro Diagnosis of Immediate Drug Hypersensitivity During Anesthesia: A Review
      of the Literature.
AB  - Quantification of specific IgE (sIgE) antibodies constitutes an important measure
      to document anesthesia-related immediate hypersensitivity reactions (IHRs).
      However, only a few drug-specific assays are available and their predictive value
      is not known. In cases of non-IgE mediated IHRs, diagnosis might benefit from
      cellular tests such as basophil mediator release tests and basophil activation
      tests (BATs). To review the potential and limitations of quantification of sIgE,
      mediator release, and BAT in anesthesia-related IHRs, a literature search was
      conducted using the key words allergy, basophil activation, CD63, CD203c,
      diagnosis, drugs, hypersensitivity, flow cytometry, MRGPRX2, specific IgE
      antibodies, leukotrienes, histamine, and tryptase; this was complemented by the
      authors' experience. The drugs and compounds that have predominantly been studied
      are neuromuscular blocking agents (NMBAs), beta-lactams, latex, and
      chlorhexidine. For sIgE NMBA, sensitivity and specificity varies between 38.5% to
      92% and 92% to 100%, respectively. For sIgE beta-lactams, sensitivity varies
      between 0% to 85% and specificity between 52% to 100%. sIgE to morphine should
      not be used in isolation to diagnose IHRs to NMBAs or opiates. sIgE for latex,
      and, in difficult cases, molecular diagnosis with quantification of sIgE to Hevea
      components constitute reliable diagnostics. For drugs, the sensitivity of BAT
      varies between 50% and 60% and specificity reaches 80% to 90%. Basophil mediator
      release tests seem to be abandoned and supplanted by BATs.

PMID- 29454710
TI  - Experiences of guilt, shame and blame in those affected by burns: A qualitative
      systematic review.
AB  - BACKGROUND: A significant burn can severely impact the lives of survivors and
      their carers. This systematic review sought to incorporate the experiences of
      guilt, blame and shame across the lifespan for burn survivors, their families as
      well as the experiences of the parents of burned children. METHODS: A systematic
      review of qualitative studies on the experiences and perspectives of guilt, blame
      and shame by those affected by burn trauma across the lifespan. The databases,
      Pubmed, Scopus, EMBASE, CINAHL, PsychINFO were systematically searched. Authors
      independently rated the reporting of the qualitative studies included. Thematic
      synthesis was used to analyse the data. The search identified 230 papers.
      Eighteen research papers met the study inclusion criteria. RESULTS: Guilt and
      ruminations of guilt, blame attribution and shame and body image were identified
      during thematic analysis as pivotal factors across the lifespan for burn
      survivors, their families as well as the experiences of the parents of burn
      injured children. Accounts presented, suggest that the impact of burns on the
      lives of the survivor and family covers a diverse spectrum of impact; personal,
      cultural and societal. CONCLUSION: From the findings of the literature searches
      and the post-burn experiences described in this review there is a gap in the
      psychological care for burn survivors and their caregivers. This is specifically
      relevant around issues of parental guilt and blame, ruminations of guilt and
      shame as well as body image. These findings may not be new to burns professionals
      but the key message is that management of these issues fall short of delivering
      comprehensive post trauma care. Identifying and highlighting the importance of
      residual psychosocial problems will ultimately influence positive outcomes for
      burn survivors.

PMID- 29454711
TI  - Outcomes of post burn flexion contracture release under tourniquet versus
      tumescent technique in children.
AB  - OBJECTIVE: To compare the clinical outcomes of release of flexion contractures
      after burn of the hand in children using tourniquet or tumescent technique in
      terms of operative time, postoperative pain score, and percentage of graft take.
      METHODS: Patients aged 3 to 12 years who required release of post-burn flexion
      contractures involving volar aspect of palm and fingers were enrolled from
      outpatient clinic. Patients were randomized in 1:1 ratio to the use of either
      tumescent technique or tourniquet during contracture release. Duration of
      procedure, postoperative pain score, percentage of graft take, and any
      complications were assessed and analyzed in both groups by a blinded observer.
      RESULTS: Of the 160 patients randomized in the study (80 in each group), 84
      (52.5%) were males. The mean+/-SD age of participants was 7.84+/-3.49 years, with
      no statistically significant difference in gender and age distribution between
      the groups. Similarly, there was no statistically significant difference in
      duration of surgery in both groups. However, there was a statistically
      significant difference in percentage of graft take at the 14th postoperative day;
      significantly more graft take was noted in the tumescent group (8.97+/-3.7cm vs.
      7.26+/-2.6cm; P=0.001). Mean analgesia consumed in the tumescent group was
      significantly less than that of the tourniquet group (6.26+/-1.9mg vs. 9.41+/
      2.2mg; P<=0.001). Similarly, statistically significant difference in the mean
      FLACC pain score was noted, with remarkably low pain score in the tumescent
      group. CONCLUSION: We found that the use of the tumescent technique for the
      release of flexion contracture resulted in better graft take, lower pain scores,
      and lesser consumption of analgesic than the use of tourniquet.

PMID- 29454712
TI  - Pre-burn malnutrition increases operative mortality in burn patients who undergo
      early excision and grafting in a sub-Saharan African burn unit: Methodological
      issues.

PMID- 29454713
TI  - The Red Journal's Top Downloads of 2016.

PMID- 29454714
TI  - Interphysician Differences in Emergency Department Length of Stay.
AB  - BACKGROUND: Emergency physicians differ in many ways with respect to practice.
      One area in which interphysician practice differences are not well characterized
      is emergency department (ED) length of stay (LOS). OBJECTIVE: To describe how ED
      LOS differs among physicians. METHODS: We performed a 3-year, five-ED
      retrospective study of non-fast-track visits evaluated primarily by physicians.
      We report each provider's observed LOS, as well as each provider's ratio of
      observed LOS/expected LOS (LOSO/E); we determined expected LOS based on site
      average adjusted for the patient characteristics of age, gender, acuity, and
      disposition status, as well as the time characteristics of shift, day of week,
      season, and calendar year. RESULTS: Three hundred twenty-seven thousand, seven
      hundred fifty-three visits seen by 92 physicians were eligible for analysis. For
      the five sites, the average shortest observed LOS was 151 min (range 106-184
      min), and the average longest observed LOS was 232 min (range 196-270 min); the
      average difference was 81 min (range 69-90 min). For LOSO/E, the average lowest
      LOSO/E was 0.801 (range 0.702-0.887), and the average highest LOSO/E was 1.210
      (range 1.186-1.275); the average difference between the lowest LOSO/E and the
      highest LOSO/E was 0.409 (range 0.305-0.493). CONCLUSION: There are significant
      differences in ED LOS at the level of the individual physician, even after
      accounting for multiple confounders. We found that the LOSO/E for physicians with
      the lowest LOSO/E at each site averaged approximately 20% less than predicted,
      and that the LOSO/E for physicians with the highest LOSO/E at each site averaged
      approximately 20% more than predicted.

PMID- 29454715
TI  - [Sleepiness, continuous positive airway pressure and the obstructive sleep apnea
      hypopnea syndrome].
AB  - Excessive daytime sleepiness is a major symptom in cases of the obstructive sleep
      apnea-hypopnea syndrome. Most often, it is vastly improved by treatment with
      continuous positive airway pressure (CPAP). The most effective way to confirm its
      disappearance is through wakefulness maintenance testing. If residual sleepiness
      remains, despite CPAP, further diagnostic investigation must be carried out.
      Firstly, it must be assessed whether the treatment is fully effective (apnea
      hypopnea index<10/h) by examining flow limitations under treatment
      (polysomnography) and whether it is sufficiently used (>6h/night). If this is the
      case, the possibility of other situations responsible for excessive daytime
      sleepiness must be reviewed and eliminated, whether they are depression, sleep
      insufficiency, use of intoxicants, obesity, restless legs syndrome, or circadian
      sleep-wake cycle disorder. If not, the multiple sleep latency tests make it
      possible to assess sleepiness (latency<8min) and can lead to a diagnosis of
      central hypersomnia (narcolepsy, idiopathic hypersomnia, hypersomnia due to a
      medical pathology). In some rare cases (about 6% of patients) investigations will
      reveal central hypersomnia due to the obstructive sleep apnea-hypopnea syndrome
      or "lesional" hypersomnia due to intermittent hypoxia. Since 2011, medications
      treating excessive sleepiness have had marketing authorization only for
      narcolepsy in France. However, they can be administered by way of derogation to
      other neurological hypersomnias on prescription by a reference centre or a centre
      with expertise in hypersomnia.

PMID- 29454716
TI  - Emergency Management of Priapism in the United Kingdom: A Survey of Current
      Practice.
AB  - BACKGROUND: Despite its importance, current practice in the emergency management
      of priapism in the United Kingdom is unknown. AIM: To evaluate current practice
      in the emergency management of priapism in the United Kingdom. METHODS: All
      "full," "associate urological specialist," and "trainee" members of the British
      Association of Urological Surgeons (BAUS; leading membership-based organization
      for practitioners of urologic surgery in the United Kingdom) were invited to
      participate in an online survey. Questions related to the emergency management of
      priapism, access to tertiary andrology services, and use of guidelines. OUTCOMES:
      Key outcome measures included frequency of encountered cases, access to
      specialist andrology support, confidence in key management steps, and use of
      current guidelines. RESULTS: 213 of 1,304 (16.3%) eligible members completed the
      survey. Most reported managing 1 case annually (median = 1, range = 0->10). Only
      7.0% transferred patients to a tertiary center and 87.8% believed they could
      access specialist andrology advice if required. Respondents were less confident
      in performing intracavernosal phenylephrine instillation (88.7%) compared with
      corporal aspiration (98.1%), with confidence lowest among trainee members. Only
      68.5% reported performing the distal shunt procedure. Of the 212 respondents that
      chose to answer questions relating to guidelines, only 155 (73.1%) were aware of
      their existence, with those published by the European Association of Urology
      being most popular (53.8%). 205 (96.2%) respondents expressed an interest in the
      development of a UK-specific guideline, with 162 of 212 (76.4%) stating they
      would use this in practice. CLINICAL IMPLICATIONS: Urologists in the United
      Kingdom support the development of UK-specific guidance on the emergency
      management of priapism for use within the context of the National Health Service.
      STRENGTHS AND LIMITATIONS: This is the first study to assess current practice in
      the emergency management of priapism in the United Kingdom. Its strength is that
      most UK urologists were invited to participate through collaboration with the
      BAUS. Although the response rate of 16.3% is acceptable for a national survey of
      this nature, responses were self-reported, rendering them susceptible to bias.
      CONCLUSION: This study demonstrates that some UK urologists lack confidence in
      key steps in the emergency management of priapism and identifies a strong level
      of support for the development of up-to-date UK-specific guidance. Bullock N,
      Steggall M, Brown G. Emergency Management of Priapism in the United Kingdom: A
      Survey of Current Practice. J Sex Med 2018;15:476-479.

PMID- 29454717
TI  - Superior Approach for Supracardiac Total Anomalous Pulmonary Venous Connection.
AB  - BACKGROUND: Studies on the outcomes of surgical repair for supracardiac total
      anomalous pulmonary venous connection through the superior approach are uncommon.
      METHODS: From January 2004 to January 2016, 198 patients with supracardiac total
      anomalous pulmonary venous connection underwent side-to-side anastomosis between
      the common pulmonary vein and left atrium through the superior approach. Kaplan
      Meier curve was used to demonstrate the survival estimates. Cox proportional
      hazard model and competing risk regression model were used to identify risk
      factors for death and postoperative pulmonary venous obstruction. RESULTS: There
      were six in-hospital deaths and no late deaths. The survival rates at 30 days, 1
      year, and 12 years were 97%, 97%, and 97%, respectively. Follow-up was completed
      in 92.2% of the survivors. Median follow-up was 47 months (range: 0 to 136
      months). Twenty-seven patients (14.1%, 27 of 192) required reoperation for
      pulmonary venous obstruction, residual atrial septal defect, or superior cava
      vena syndrome. Multivariable analysis showed that preoperative pulmonary venous
      obstruction (p = 0.012), longer duration of ventilation (p = 0.011), and
      emergency operation (p = 0.010) were incremental risk factors for death. Aortic
      cross-clamp time (p < 0.001) and preoperative pulmonary venous obstruction (p =
      0.002) were associated with postoperative pulmonary venous obstruction.
      CONCLUSIONS: Side-to-side anastomosis through a superior approach in surgical
      repair of supracardiac total anomalous pulmonary venous connection can achieve
      satisfactory results.

PMID- 29454718
TI  - Learning Curve for Robot-Assisted Minimally Invasive Thoracoscopic Esophagectomy:
      Results From 312 Cases.
AB  - BACKGROUND: Thoracic laparoscopic robot-assisted minimally invasive esophagectomy
      (RAMIE) was developed in 2003. RAMIE was shown to be safe and oncologically
      effective. The aim of this study was to assess the learning curve and the
      proctoring program for a newly introduced surgeon (surgeon 2). METHODS: The
      "learning curve" was defined as the number of operations that must be performed
      by a surgeon to achieve a steady level of performance. Measures of proficiency to
      describe the learning curve of the proctor and the newly introduced surgeon 2
      included operating time, blood loss, and conversion rates and were analyzed using
      the cumulative sum method. Results of the newly introduced surgeon were compared
      with the proctor in the same period of time. RESULTS: The proctor performed 232
      of 312 procedures (74%) and surgeon 2 performed 80 of 312 procedures (26%). The
      proctor reached proficiency after 70 procedures in 55 months. The structured
      proctoring program for surgeon 2 started with 20 procedures as assisting table
      surgeon, followed by 5 observational and 15 supervised cases. Surgeon 2 performed
      at the same level as the proctor concerning operating time, blood loss,
      conversion rates, radicality, and complications. For surgeon 2, the learning
      phase of thoracic laparoscopic RAMIE was completed within 24 cases (15 supervised
      and 9 independent cases) in 13 months; a reduction of 66% in the number of
      operations and a reduction of 76% in time, compared with the proctor.
      CONCLUSIONS: The learning phase of thoracic laparoscopic RAMIE consisted of 70
      procedures in 55 months. A structured proctoring for RAMIE substantially reduced
      the number of procedures and time required to achieve proficiency.

PMID- 29454719
TI  - Supply Shortages: A Silver Lining.

PMID- 29454720
TI  - Shared Clinical Truths.

PMID- 29454721
TI  - Extensive Iliofemoral Occlusion After Aortobifemoral Bypass Occlusion: The
      Potential of Native Artery Recanalization.

PMID- 29454722
TI  - Quadriostial Origin of 4 Coronary Arteries From the Right Coronary Sinus of
      Valsalva: Rare Anomaly.

PMID- 29454723
TI  - To EncourAGE Individualized Dual Antiplatelet Therapy Duration After Drug-Eluting
      Stent Implantation: A New pAGE of an Intriguing Book.

PMID- 29454724
TI  - "Silent" Diabetes and Clinical Outcome After Treatment With Contemporary Drug
      Eluting Stents: The BIO-RESORT Silent Diabetes Study.
AB  - OBJECTIVES: This study sought to assess the prevalence and clinical impact of
      silent diabetes and pre-diabetes in "nondiabetic" percutaneous coronary
      intervention (PCI) all-comers. BACKGROUND: Patients with undetected and thus
      untreated (silent) diabetes may have higher event risks after PCI with
      contemporary drug-eluting stents (DES). METHODS: The BIO-RESORT Silent Diabetes
      study, performed at Thoraxcentrum Twente, is a substudy of the randomized
      multicenter BIO-RESORT (BIOdegradable Polymer and DuRable Polymer Drug-eluting
      Stents in an All COmeRs PopulaTion) trial (NCT01674803). Patients underwent oral
      glucose tolerance testing (OGTT), and assessment of glycosylated hemoglobin with
      fasting plasma glucose. Primary endpoint was a composite of cardiac death, target
      vessel-related myocardial infarction, or target vessel revascularization at 1
      year. RESULTS: Of the 988 participants, OGTT detected silent diabetes in 68
      (6.9%), pre-diabetes in 133 (13.3%), and normal glucose metabolism in 788
      (79.8%). Patients with silent diabetes had higher primary endpoint rates (13.2%
      vs. 7.6% vs. 4.8%; p < 0.001; silent diabetes vs. normal: hazard ratio: 4.2; 95%
      confidence interval: 1.9 to 9.2). Differences were driven by myocardial
      infarction (p < 0.001) which occurred mostly <48 h. Based on glycosylated
      hemoglobin and fasting plasma glucose, silent diabetes was found in 33 (3.3%)
      patients, pre-diabetes in 217 (22.0%) patients, and normal glucose metabolism in
      738 (74.7%) patients; primary endpoint rates were similar to OGTT-based analyses
      (12.1% vs. 5.5% vs. 3.1%; p = 0.01). Multivariate analyses demonstrated that
      abnormal glucose metabolism by either diagnostic approach, present in 330 (33.4%)
      patients, independently predicted adverse event risk (hazard ratio: 2.2; 95%
      confidence interval: 1.2 to 4.2). CONCLUSIONS: Abnormal glucose metabolism was
      detected in 1 of 3 "nondiabetic" PCI patients and was independently associated
      with up to 4-fold higher event risks. Future intervention trials should determine
      whether meaningful benefits accrue from routine glycemia testing in such
      patients.

PMID- 29454725
TI  - Suboptimal Bifurcation Stenting: A Case When the Check Comes Late.

PMID- 29454726
TI  - Successful Percutaneous Retrieval of a 33-mm Watchman Left Atrial Appendage
      Occlusion Device From the Left Atrium.

PMID- 29454727
TI  - Emergency Treatment of a Ruptured Giant Aneurysm in a Saphenous Vein Graft.

PMID- 29454728
TI  - First Report of Drug-Coated Balloon Angioplasty for Vertebral Artery Origin
      Stenosis.

PMID- 29454729
TI  - Moving Beyond the Stent: Identifying the Percutaneous Coronary Intervention
      Patient With Silent Diabetes and Pre-Diabetes.

PMID- 29454730
TI  - Short-Term Versus Long-Term Dual Antiplatelet Therapy After Drug-Eluting Stent
      Implantation in Elderly Patients: A Meta-Analysis of Individual Participant Data
      From 6 Randomized Trials.
AB  - OBJECTIVES: This study sought to evaluate the optimal duration of dual
      antiplatelet therapy (DAPT) after the implantation of a drug-eluting stent (DES)
      in elderly patients. BACKGROUND: Qualified studies to evaluate the optimal
      duration of DAPT in elderly patients have been very limited. METHODS: Using 6
      randomized trials that compared short-term (<=6 months) and long-term (12 months)
      DAPT, individual participant data meta-analysis was performed in elderly patients
      (>=65 years of age). The primary study outcome was the 12-month risk of a
      composite of myocardial infarction, definite or probable stent thrombosis, or
      stroke. The major secondary outcome was the 12-month risk of major bleeding.
      RESULTS: The primary outcome risk did not significantly differ between patients
      receiving short-term and long-term DAPT (hazard ratio [HR]: 1.12; 95% confidence
      interval [CI]: 0.88 to 1.43; p = 0.3581) in the overall group of study
      participants. In subgroup analysis, a significant interaction between age and
      DAPT duration was observed for primary outcome risk (p for interaction = 0.0384).
      In the subset of younger patients (<65 years of age, n = 6,152), short-term DAPT
      was associated with higher risk of primary outcome (HR: 1.67; 95% CI: 1.14 to
      2.44; p = 0.0082). In elderly patients (n = 5,319), however, the risk of primary
      outcome did not significantly differ between patients receiving short-term and
      long-term DAPT (HR: 0.84; 95% CI: 0.60 to 1.16; p = 0.2856). Short-term DAPT was
      associated with a significant reduction in major bleeding compared with long-term
      DAPT (HR: 0.50; 95% CI: 0.30 to 0.84; p = 0.0081) in the overall group, and
      particularly in elderly patients (HR: 0.46; 95% CI: 0.24-0.88; p = 0.0196).
      CONCLUSIONS: Short-term DAPT after new-generation DES implantation may be more
      beneficial in elderly patients than in younger patients.

PMID- 29454731
TI  - Significance of novel subcortical low intensity score on transient neurological
      events after revascularization surgery for moyamoya disease.
AB  - OBJECTIVES: Transient neurological events (TNEs) are frequently observed after
      revascularization surgery for moyamoya disease (MMD). Recently, two signs on
      fluid-attenuated inversion recovery magnetic resonance images, a cortical
      hyperintensity belt (CHB) sign possibly reflecting vasogenic edema and a
      transient subcortical low intensity (SCLI) sign possibly reflecting cytotoxic
      edema, were reported associated with TNEs. The purpose of this study was to
      create a SCLI score and to investigate the significance of the score in TNEs.
      PATIENTS AND METHODS: The authors retrospectively analyzed 18 cerebral
      hemispheres in 16 consecutive patients with revascularization surgery for MMD.
      The SCLI sign was defined as a transient SCLI in surgically treated hemispheres,
      and blindly graded as the SCLI score (0-4) based on the extent. The relationships
      among SCLI, CHB signs and TNEs were evaluated. RESULTS: Postoperative TNEs, SCLI
      and CHB signs were detected in 8 (44.4%), 9 (50.0%) and 12 (66.7%) hemispheres,
      respectively. Patients with SCLI and CHB signs had a significantly higher TNE
      occurrence rate than those without these signs (p = 0.015, and p = 0.013,
      respectively). Patients with TNEs showed significantly higher SCLI scores than
      those without TNEs (p = 0.009), while the difference of CHB scores did not reach
      significance between patients with and without TNEs. For the occurrence of
      postoperative TNEs, SCLI score with a cut-off value of 1.0 resulted in a
      specificity of 80.0% and a sensitivity of 87.5%. CONCLUSION: The novel SCLI score
      may be useful for diagnosing TNEs after revascularization surgery for MMD,
      although both vasogenic and cytotoxic edema may be involved in postoperative
      TNEs.

PMID- 29454732
TI  - Genetic interaction and diversity of the families Libellulidae and Gomphidae
      through COI gene from China and Pakistan.
AB  - A total of 300 dragonflies (Odonata) were collected from six different localities
      of China and Pakistan. Sixty seven representative samples were selected to
      sequence their mitochondrial cytochrome oxidase subunit I (COI). An examination
      of the resultant sequences identified 21 different dragonfly species, belonging
      to 15 distinct genera, two families, Libellulidae and Gomphidae. Sequence
      alignment was executed using Clustal-W in BioEdit v6. The phylogenetic tree was
      constructed through Neighbor-joining method by using Jukes-Cantor model, and
      genetic divergence was calculated via Kimura 2-parameter using MEGA7, while
      Genetic diversity was calculated by DnaSP v5. The maximum genetic divergence was
      observed for Crocothemis servilia, at 20.49%, followed by Libellulidae sp. with
      22.30% while minimum divergence (0.82%) was observed for Melligomphus ardens.
      Likewise, a significant genetic diversity was observed for all species. However,
      Crocothemis servilia species presented maximum value (176 mutations) followed by
      Libellulidae spp. (150 mutations), whereas minimum value (3 mutations) was
      observed by Orthetrum testaceum. Interestingly, the diversity of C. servilia, all
      of which are collected from a single location of China, is much higher than those
      from Pakistan, which were collected from 5 different places with a spatial
      distance exceeding 500 Kms. Our results are useful in gaining a full appreciation
      of the global diversity of dragonflies and the development of conservation
      measures of this insect.

PMID- 29454733
TI  - Characterization of fungus microbial diversity in healthy and diarrheal yaks in
      Gannan region of Tibet Autonomous Prefecture.
AB  - Diarrhea is a serious epidemic in yaks on Qinghai Tibet plateau, but the exact
      pathogen is not confirmed. Diarrhea is related to the changes in diversity of
      intestinal flora. The current study herein is performed for high-throughput
      sequencing of fungus microbial diversity in healthy adult yaks, diarrheal adult
      yaks and diarrheal yak calves in Gannan Tibetan Autonomous Prefecture. A total
      446726 optimized sequences were achieved. Over 250 OTUs in species level have
      been indentified for each sample. The Shannon and Simpson index revealed that
      there was no visible difference in the flora between different yak groups (p >
      0.05). However, obvious difference was watched in the principal component of
      microbial community structure in different yak groups by PCA analysis, especially
      between healthy adult yak group and diarrheal adult yak groups. There were 248
      fungus species shared in three groups. Interestingly, there were 97 fungus
      species shared in the diarrheal groups (calves and adult yaks), which were not
      found in the healthy yaks, while there were 212 fungus species only found in the
      healthy yaks. In the Phylum level, 1 phylum (Neocallimastigomycota) was
      discovered to have significant difference between healthy yaks and diarrheal yak
      calves (p < 0.05). In the genus level, 23 genus were found obvious difference
      between healthy adult yaks and diarrheal adults yaks (p < 0.05); 28 genus were
      found significant difference between healthy adult yaks and diarrheal yak calves
      (p < 0.05); 23 genus were found obvious difference between diarrheal adult yaks
      and diarrheal yak calves (p < 0.05). The present study herein first reported an
      insight of the change of microbial diversity of fungus in diarrhea yaks at
      altitude regions, which contributed towards the solid prevention of diarrhea in
      yaks.

PMID- 29454734
TI  - Management of arthropod vector data - Social and ecological dynamics facing the
      One Health perspective.
AB  - Emerging infectious diseases (EIDs) are spread by direct and/or indirect contacts
      between a pathogen or parasite and their hosts. Arthropod vectors have evolved as
      excellent bloodsuckers, providing an elegant transportation mode for a wide
      number of infectious agents. The nature of pathogen and parasite transfer and the
      models used to predict how a disease might spread are magnified in complexity
      when an arthropod vector is part of the disease cycle. One Health is a worldwide
      strategy for expanding interdisciplinary collaborations and communications in all
      aspects of health care for humans, animals and the environment. It would benefit
      from a structured analysis to address vectoring of arthropod-borne diseases as a
      dynamic transactional process. This review focused on how arthropod vector data
      can be used to better model and predict zoonotic disease outbreaks. With enhanced
      knowledge to describe arthropod vector disease transfer, researchers will have a
      better understanding about how to model disease outbreaks. As public health
      research evolves to include more social-ecological systems, the roles of society,
      ecology, epidemiology, pathogen/parasite evolution and animal behavior can be
      better captured in the research design. Overall, because of more collaborative
      data collection processes on arthropod vectors, disease modeling can better
      predict conditions where EIDs will occur.

PMID- 29454736
TI  - Editorial -March issue surgical oncology.

PMID- 29454735
TI  - Metaperiodate deglycosylation of Strongyloides venezuelensis larvae:
      Immunochemical characterization and antigen production for human strongyloidiasis
      diagnosis.
AB  - Strongyloidiasis is an important helminthiasis affecting million people
      worldwide. The aim of this study was to use sodium metaperiodate (MP) treatment
      to immunochemically characterize Strongyloides venezuelensis filariform larvae
      and use MP-treated heterologous antigen to detect IgG and subclasses in serum.
      Samples from individuals with definitive diagnosis of strongyloidiasis (n = 50),
      other parasitic diseases (n = 60) and negative endemic (n = 50) were tested. TG
      ROC and two-way ANOVA were applied. MP-treatment resulted on differential
      localization of carbohydrates at larval structure and no carbohydrate content in
      saline extract (SE). Electrophoretic profiles were similar before and after
      treatment. ELISA sensitivity and specificity were: 90%; 88.2% for SE and 92.0%;
      94.6% for MP, respectively. When using MP treated antigen we observed reduction
      in IgG1 and IgG3 detection in strongyloidiasis group and decrease of cross
      reactions in control groups. Our data demonstrate the role of carbohydrate
      residues in cross reactions and on the recognition of anti-Strongyloides IgG and
      its subclasses.

PMID- 29454737
TI  - Adjuvant radiotherapy for positive lymph nodes of oesophageal squamous cell
      carcinoma: Can it earn promising benefits at long-term follow-up?
AB  - PURPOSE: The value of adjuvant radiotherapy for patients with positive lymph
      nodes after curative resection of oesophageal squamous cell carcinoma is
      controversial. This study aims to investigate its long-term benefits in a
      specific cohort. PATIENTS AND METHODS: The charts between 1990 and 2003 from
      patients with positive lymph nodes were retrospectively reviewed. Those subjects
      were divided into adjuvant radiotherapy and surgery alone groups, with two
      subgroups defined by radiation dose (cutoff value: 50Gy). Overall survival,
      disease-free survival and locoregional recurrence-free survival were compared
      between two groups, with predictive factors of overall survival analysed
      meanwhile. RESULTS: In sum, 175 matched patients with 1:2 ratios for group
      balance were enrolled for final analysis. During the follow-up (median: 37.0
      months), 143 (81.7%) deaths were recorded, with 70.6% of deaths from cancer
      progression. The median overall survival time (19.5, 4 to 172 months) was not
      significantly different between the two groups (18.9 vs. 20.0 months, P=0.179).
      However, the disease-free survival time was significantly shorter in the adjuvant
      radiotherapy group than that in the control group (median, 11.5 vs. 14.9 months;
      P=0.001), with the locoregional recurrence-free survival time impressively
      prolonged (median: 18.3 vs. 16.5 months; P=0.022). Age (P=0.030), number
      (P=0.005) and ratio (P=0.002) of positive lymph nodes were associated with
      overall survival, but radiation dose was not (P=0.204). CONCLUSION: Adjuvant
      radiotherapy with low- or high-dose did not improve survival compared with
      surgery alone. However, radiotherapy was effective to control locoregional
      recurrence, and could be applied as salvage therapy when recurrence event
      occurred.

PMID- 29454738
TI  - [Satellite center of human milk: Analysis of cost reduction].
AB  - INTRODUCTION: Donor milk is the second best alternative for a newborn after the
      mother's own milk, especially when the baby is a premature or a sick child since
      this milk has the advantage of protecting against necrotizing enterocolitis.
      There are currently 13 milk banks in Spain, however this is not sufficient to
      supply all Spanish neonatal units with donor milk. In order to bring donor milk
      to the babies in Neonatal Unit of the Regional University Hospital of Malaga, a
      Satellite Centre (CS) was created in 2012, depending on the Milk Bank of Virgen
      de las Nieves Hospital in Granada. AIM: Assessing the efficiency of a SC compared
      to an independent milk bank. METHOD: A study of cost minimization is used for the
      analysis. The cost of the implementation of the SC is calculated and compared to
      the cost of the implementation of the Milk Bank of Virgen de las Nieves of
      Granada. Additionally, the maintenance cost per year of the 2 models is compared,
      taking into account the running phase from June, 2012 through August 2015 in the
      SC. RESULTS: A SC implies savings of 88,852 Euro in equipment, and 24,572 Euro
      per year in maintenance compared to an independent milk bank. CONCLUSIONS: The
      efficiency of the SC is due to a better use of resources. A distribution network
      model of donor human milk, consisting of milk banks and SC, makes it possible to
      equally supply human milk to premature infants with a reduced cost.

PMID- 29454740
TI  - A rapid point-of-care test for dengue virus-1 based on a lateral flow assay with
      a near-infrared fluorescent dye.
AB  - Dengue fever is caused by the dengue virus (DENV), and DENV1 is the prevalent
      epidemic serotype in south China. A new lateral flow assay (LFA) based on a near
      infrared (NIR) fluorescent dye was developed to detect anti-DENV1 IgG antibodies.
      DyLight-800 was used as the marker conjugated to goat anti-human IgG antibodies,
      and recombinant dengue type 1 envelope protein was used as the capture protein on
      the test line. Twenty samples from patients infected with DENV1 and 160 negative
      controls were analyzed using this new NIR-LFA. The results of the NIR-LFA were
      compared with the results of Panbio Dengue IgG ELISA and the Dengue Duo IgM/IgG
      Cassette. Nineteen confirmed DENV1-positive samples were identified by NIR-LFA,
      giving 95% (19/20) sensitivity. No significant differences existed in the results
      when the 20 primary clinical samples were analyzed using NIR-LFA, Panbio ELISA,
      and the Dengue Duo Cassette. However, NIR-LFA had a lower limit of detection than
      IgG ELISA and Duo IgM/IgG Cassette did when analyzing a 2-fold dilution series of
      the 19 samples positively identified by NIR-LFA. When incorporated with an NIR
      POCT device, the new NIR-LFA was rapid, easy to use, and highly sensitive in
      detecting DENV1, and has potential for application to clinical diagnosis.

PMID- 29454739
TI  - Spanish and Catalan translation, cultural adaptation and validation of the Picker
      Patient Experience Questionnaire-15.
AB  - OBJECTIVE: To develop and test a culturally adapted core set of questions to
      measure patients' experience after in-patient care. MATERIAL AND METHODS:
      Following the methodology recommended by international guides, a basic set of
      patient experience questions, selected from Picker Institute Europe
      questionnaires (originally in English), was translated to Spanish and Catalan.
      Acceptability, construct validity and reliability of the adapted questionnaire
      were assessed via a cross-sectional validation study. The inclusion criteria were
      patients aged >18 years, discharged within one week to one month prior to
      questionnaire sending and whose email was available. Day cases, emergency
      department patients and deaths were excluded. Invitations were sent by email
      (N=876) and questionnaire was fulfilled through an online platform. An automatic
      reminder was sent 5 days later to non-respondents. RESULTS: A questionnaire, in
      Spanish and Catalan, with adequate conceptual and linguistic equivalence was
      obtained. Response rate was 44.4% (389 responses). The correlation matrix was
      factorable. Four factors were extracted with Parallel Analysis, which explained
      43% of the total variance. First factor: information and communication received
      during discharge. Second factor: low sensitivity attitudes of professionals.
      Third factor: assessment of communication of medical and nursing staff. Fourth
      factor: global items. The value of the Cronbach alpha was 0.84, showing a high
      internal consistency. CONCLUSIONS: The obtained experience patient questionnaire,
      in Spanish and Catalan, shows good results in the psychometric properties
      evaluated and could be a useful tool to identify opportunities for health care
      improvement in our context. Email could become a feasible tool for greater
      patient participation in everything that concerns his health.

PMID- 29454741
TI  - Exploiting or overcoming the dome trap for enhanced oral immunization and drug
      delivery.
AB  - The microfold cells (M cells) residing in the outmost follicle-associated
      epithelia (FAE) of Peyer's patches capture foreign particles and hand over to sub
      FAE lymphatics, where the particles are retained and disposed subsequently. A
      concept of "dome trap" is proposed to highlight the significance of this
      mechanism. For oral immunization, it is better to exploit the entrapment capacity
      to maximize immune response, whereas for drug delivery it is better to overcome
      the dome trap to transport drugs into the systemic circulation. By optimizing the
      size, shape, surface charges and surface properties of particles, either oral
      immunization or drug delivery can be potentially enhanced.

PMID- 29454742
TI  - Tumor target amplification: Implications for nano drug delivery systems.
AB  - Tumor cells overexpress surface markers which are absent from normal cells. These
      tumor-restricted antigenic signatures are a fundamental basis for distinguishing
      on-target from off-target cells for ligand-directed targeting of cancer cells.
      Unfortunately, tumor heterogeneity impedes the establishment of a solid
      expression pattern for a given target marker, leading to drastic changes in
      quality (availability) and quantity (number) of the target. Consequently, a
      subset of cancer cells remains untargeted during the course of treatment, which
      subsequently promotes drug-resistance and cancer relapse. Since target
      inefficiency is only problematic for cancer treatment and not for treatment of
      other pathological conditions such as viral/bacterial infections, target
      amplification or the generation of novel targets is key to providing eligible
      antigenic markers for effective targeted therapy. This review summarizes the
      limitations of current ligand-directed targeting strategies and provides a
      comprehensive overview of tumor target amplification strategies, including self
      amplifying systems, dual targeting, artificial markers and peptide modification.
      We also discuss the therapeutic and diagnostic potential of these approaches, the
      underlying mechanism(s) and established methodologies, mostly in the context of
      different nanodelivery systems, to facilitate more effective ligand-directed
      cancer cell monitoring and targeting.

PMID- 29454743
TI  - Corrigendum to "Precision medicine for patients with advanced biliary tract
      cancers: An effective strategy within the prospective MOSCATO-01 trial" [Eur J
      Cancer 87 (2017) 122-130].

PMID- 29454744
TI  - European Academy of Cancer Sciences-Designation of Comprehensive Cancer Centres
      of Excellence.

PMID- 29454745
TI  - New ADCY3 Variants Dance in Obesity Etiology.
AB  - The genetic etiology for obesity-related traits remains elusive. Recent studies
      link novel ADCY3 variants to obesity and diabetes, and identify an important role
      of ADCY3-mediated signaling at neuronal primary cilia in the predisposition of
      obesity. These findings provide new information on obesity etiology and suggest
      potential anti-obesity therapeutic strategies.

PMID- 29454746
TI  - Phosphodiesterase inhibition and modulation of corticostriatal and hippocampal
      circuits: Clinical overview and translational considerations.
AB  - The corticostriatal and hippocampal circuits contribute to the neurobiological
      underpinnings of several neuropsychiatric disorders, including Alzheimer's
      disease, Parkinson's disease and schizophrenia. Based on biological function,
      these circuits can be clustered into motor circuits, associative/cognitive
      circuits and limbic circuits. Together, dysfunctions in these circuits produce
      the wide range of symptoms observed in related neuropsychiatric disorders.
      Intracellular signaling in these circuits is largely mediated through the cyclic
      adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway with an additional
      role for the cyclic guanosine monophosphate (cGMP)/ protein kinase G (PKG)
      pathway, both of which can be regulated by phosphodiesterase inhibitors (PDE
      inhibitors). Through their effects on cAMP response element-binding protein
      (CREB) and Dopamine- and cAMP-Regulated PhosphoProtein MR 32 kDa (DARPP-32),
      cyclic nucleotide pathways are involved in synaptic transmission, neuron
      excitability, neuroplasticity and neuroprotection. In this clinical review, we
      provide an overview of the current clinical status, discuss the general mechanism
      of action of PDE inhibitors in relation to the corticostriatal and hippocampal
      circuits and consider several translational challenges.

PMID- 29454747
TI  - Plasminogen Activator Inhibitor-1 Reduces Tissue-Type Plasminogen Activator
      Dependent Fibrinolysis and Intrahepatic Hemorrhage in Experimental Acetaminophen
      Overdose.
AB  - Acetaminophen (APAP)-induced liver injury in mice is associated with activation
      of the coagulation cascade and deposition of fibrin in liver. Plasminogen
      activator inhibitor-1 (PAI-1) is an important physiological inhibitor of tissue
      type plasminogen activator (tPA) and plays a critical role in fibrinolysis. PAI-1
      expression is increased in both experimental APAP-induced liver injury and
      patients with acute liver failure. Prior studies have shown that PAI-1 prevents
      intrahepatic hemorrhage and mortality after APAP challenge, but the downstream
      mechanisms are not clear. We tested the hypothesis that PAI-1 limits liver
      related morbidity after APAP challenge by reducing tPA-dependent fibrinolysis.
      Compared with APAP-challenged (300 mg/kg) wild-type mice, hepatic deposition of
      cross-linked fibrin was reduced, with intrahepatic congestion and hemorrhage
      increased in PAI-1-deficient mice 24 hours after APAP overdose. Administration of
      recombinant wild-type human PAI-1 reduced intrahepatic hemorrhage 24 hours after
      APAP challenge in PAI-1-/- mice, whereas a mutant PAI-1 lacking antiprotease
      function had no effect. Of interest, tPA deficiency alone did not affect APAP
      induced liver damage. In contrast, fibrinolysis, intrahepatic congestion and
      hemorrhage, and mortality driven by PAI-1 deficiency were reduced in APAP-treated
      tPA-/-/PAI-1-/- double-knockout mice. The results identify PAI-1 as a critical
      regulator of intrahepatic fibrinolysis in experimental liver injury. Moreover,
      the results suggest that the balance between PAI-1 and tPA activity is an
      important determinant of liver pathology after APAP overdose.

PMID- 29454748
TI  - Fatty Acid Binding Protein 4 (FABP4) Overexpression in Intratumoral Hepatic
      Stellate Cells within Hepatocellular Carcinoma with Metabolic Risk Factors.
AB  - Metabolic syndrome is a newly identified risk factor for hepatocellular carcinoma
      (HCC); however, tumor-specific biomarkers still remain unclear. We performed
      cross-species analysis to compare gene signatures of HCC from human patients and
      melanocortin 4 receptor-knockout mice, which develop HCC with obesity, insulin
      resistance, and dyslipidemia. Unsupervised hierarchical clustering and principle
      component analysis of 746 differentially expressed orthologous genes classified
      HCC of 152 human patients and melanocortin 4 receptor-knockout mice into two
      distinct subgroups, one of which included mouse HCC and was causatively
      associated with metabolic risk factors. Nine genes commonly overexpressed in
      human and mouse metabolic disease-associated HCC were identified; fatty acid
      binding protein 4 (FABP4) was remarkably enriched in intratumoral activated
      hepatic stellate cells (HSCs). Subclones constitutively expressing FABP4 were
      established from a human HSC cell line in which expression levels of inflammatory
      chemokines, including IL-1A and IL-6, were up-regulated through NF-kappaB nuclear
      translocation, resulting in recruitment of macrophages. An immunohistochemical
      validation study of 106 additional human HCC samples indicated that FABP4
      positive HSCs were distributed in tumors of 38 cases, and the FABP4-high group
      consisted of patients with nonviral and nonalcoholic HCC (P = 0.027) and with
      multiple metabolic risk factors (P < 0.001) compared with the FABP4-low group.
      Thus, FABP4 overexpression in HSCs may contribute to hepatocarcinogenesis in
      patients with metabolic risk factors by modulation of inflammatory pathways.

PMID- 29454749
TI  - Microbiota-Derived Indole Metabolites Promote Human and Murine Intestinal
      Homeostasis through Regulation of Interleukin-10 Receptor.
AB  - Interactions between the gut microbiota and the host are important for health,
      where dysbiosis has emerged as a likely component of mucosal disease. The
      specific constituents of the microbiota that contribute to mucosal disease are
      not well defined. The authors sought to define microbial components that regulate
      homeostasis within the intestinal mucosa. Using an unbiased, metabolomic
      profiling approach, a selective depletion of indole and indole-derived
      metabolites was identified in murine and human colitis. Indole-3-propionic acid
      (IPA) was selectively diminished in circulating serum from human subjects with
      active colitis, and IPA served as a biomarker of disease remission.
      Administration of indole metabolites showed prominent induction of IL-10R1 on
      cultured intestinal epithelia that was explained by activation of the aryl
      hydrocarbon receptor. Colonization of germ-free mice with wild-type Escherichia
      coli, but not E. coli mutants unable to generate indole, induced colonic
      epithelial IL-10R1. Moreover, oral administration of IPA significantly
      ameliorated disease in a chemically induced murine colitis model. This work
      defines a novel role of indole metabolites in anti-inflammatory pathways mediated
      by epithelial IL-10 signaling and identifies possible avenues for utilizing
      indoles as novel therapeutics in mucosal disease.

PMID- 29454750
TI  - A Newly Discovered Antifibrotic Pathway Regulated by Two Fatty Acid Receptors:
      GPR40 and GPR84.
AB  - Numerous clinical conditions can lead to organ fibrosis and functional failure.
      There is a great need for therapies that could effectively target
      pathophysiological pathways involved in fibrosis. GPR40 and GPR84 are G protein
      coupled receptors with free fatty acid ligands and are associated with metabolic
      and inflammatory disorders. Although GPR40 and GPR84 are involved in diverse
      physiological processes, no evidence has demonstrated the relevance of GPR40 and
      GPR84 in fibrosis pathways. Using PBI-4050 (3-pentylbenzeneacetic acid sodium
      salt), a synthetic analog of a medium-chain fatty acid that displays agonist and
      antagonist ligand affinity toward GPR40 and GPR84, respectively, we uncovered an
      antifibrotic pathway involving these receptors. In experiments using Gpr40- and
      Gpr84-knockout mice in models of kidney fibrosis (unilateral ureteral
      obstruction, long-term post-acute ischemic injury, and adenine-induced chronic
      kidney disease), we found that GPR40 is protective and GPR84 is deleterious in
      these diseases. Moreover, through binding to GPR40 and GPR84, PBI-4050
      significantly attenuated fibrosis in many injury contexts, as evidenced by the
      antifibrotic activity observed in kidney, liver, heart, lung, pancreas, and skin
      fibrosis models. Therefore, GPR40 and GPR84 may represent promising molecular
      targets in fibrosis pathways. We conclude that PBI-4050 is a first-in-class
      compound that may be effective for managing inflammatory and fibrosis-related
      diseases.

PMID- 29454751
TI  - Strain-Dependent Variation in Acute Ischemic Muscle Injury.
AB  - Limited efficacy of clinical interventions for peripheral arterial disease
      necessitates a better understanding of the environmental and genetic determinants
      of tissue pathology. Existing research has largely ignored the early skeletal
      muscle injury response during hind limb ischemia (HLI). We compared the hind limb
      muscle response, after 6 hours of ischemia, in two mouse strains that differ
      dramatically in their postischemic extended recovery: C57BL/6J and BALB/cJ.
      Perfusion, measured by laser Doppler and normalized to the control limb, differed
      only slightly between strains after HLI (<12% across all measures). Similar
      (<10%) effect sizes in lectin-perfused vessel area and no differences in tissue
      oxygen saturation measured by reflectance spectroscopy were also found. Muscles
      from both strains were functionally impaired after HLI, but greater muscle
      necrosis and loss of dystrophin-positive immunostaining were observed in BALB/cJ
      muscle compared with C57BL/6J. Muscle cell-specific dystrophin loss and reduced
      viability were also detected in additional models of ischemia that were
      independent of residual perfusion differences. Our results indicate that factors
      other than the completeness of ischemia alone (ie, background genetics) influence
      the magnitude of acute ischemic muscle injury. These findings may have
      implications for future development of therapeutic interventions for limb
      ischemia and for understanding the phasic etiology of chronic and acute ischemic
      muscle pathophysiology.

PMID- 29454752
TI  - Effects of 5-Hydroxytryptamine Class 2 Receptor Antagonists on
      Bronchoconstriction and Pulmonary Remodeling Processes.
AB  - Serotonin [5-hydroxytryptamine (5-HT)] is associated with several chronic
      pulmonary diseases, recognizing 5-HT2 receptor antagonists as potential
      inhibitors of tissue remodeling. However, the effects of 5-HT2 receptors,
      especially 5-HT2B receptors on airway function and remodeling, are unclear. We
      investigated the role of 5-HT2B receptors on airway smooth muscle contractility
      and remodeling processes. Murine precision-cut lung slices were pretreated with 5
      HT2B receptor antagonists (EXT5, EXT9, RS 127445, and PRX 08066), as well as
      ketanserin (5-HT2A/2C receptor antagonist) (1, 10 MUmol/L), before addition of
      cumulative concentrations of 5-HT to induce bronchoconstriction. Remodeling
      effects after treatment with 10 MUmol/L 5-HT and 5-HT2 receptor antagonists were
      further studied in distal lung tissue by examining release of profibrotic
      transforming growth factor (TGF)-beta1 and proliferation of human bronchial
      smooth muscle cells (HBSMCs). 5-HT-induced bronchoconstriction was significantly
      reduced by EXT5, EXT9, and ketanserin, but not by RS 127445 or PRX 08066. The 5
      HT2B receptor antagonists significantly reduced TGF-beta1 release. 5-HT, in
      combination with TGF-beta1, increased proliferation of HBSMCs, a process reduced
      by EXT5 and EXT9. Our results indicate that EXT5 and EXT9 may relieve
      bronchoconstriction in murine airways and serve as an add-on effect in
      attenuating pulmonary remodeling by improving airway function. The
      antiproliferative effect on HBSMCs and the inhibition of TGF-beta1 release
      further support a role of 5-HT2B receptors in pathologic remodeling processes.

PMID- 29454753
TI  - Protein S Exacerbates Chronic Liver Injury and Fibrosis.
AB  - Protein S is a vitamin K-dependent glycoprotein produced mainly in the liver with
      anticoagulant, anti-inflammatory, immune-modulatory, and antiapoptotic
      properties. Protein S exacerbates acute liver injury by prolonging the survival
      of liver immune cells. However, the effect of protein S on chronic liver injury
      and fibrosis is unknown. Here, we investigated whether human protein S can affect
      chronic liver injury and fibrosis. Liver injury/fibrosis was induced by carbon
      tetrachloride injection in mice overexpressing human protein S and in wild-type
      mice. Human protein S transgenic mice receiving carbon tetrachloride showed
      significantly higher circulating levels of liver transaminases, increased liver
      expression of inflammatory cytokines, significantly more extended liver fibrosis,
      and areas with DNA breakage after chronic injury compared with wild-type mice.
      Wild-type mice infused with exogenous human protein S exhibited exacerbated liver
      injury and increased number of hepatic stellate cells compared with untreated
      mice. Human protein S inhibited apoptosis and increased Akt pathway activation in
      hepatic stellate cells. The antiapoptotic activity of protein S may play a role
      in chronic liver injury and subsequent liver fibrosis.

PMID- 29454754
TI  - Mutational Analysis of AKT1 and PIK3CA in Intraductal Papillomas of the Breast
      with Special Reference to Cellular Components.
AB  - The pathologic feature of intraductal papillomas is defined as a papillary
      structure composed of a fibrovascular stromal core lined by luminal epithelial
      cells and myoepithelial cells. We used droplet digital PCR for the mutational
      analysis of AKT1 (E17K) and PIK3CA (H1047R, E542K, and E545K) in 60 papillomas.
      AKT1 and PIK3CA mutations were detected in 12 (20%) and 17 (28%) of the
      papillomas, respectively. In five tumors harboring mutations, mutational analysis
      of AKT1 or PIK3CA was performed separately using luminal epithelial cells and
      myoepithelial cells sorted using anti-cytokeratin 19 antibody and anti-alpha
      smooth muscle actin antibody. The two types of cells from a given papilloma had
      the identical mutation. Three patients with the PIK3CA mutation-positive
      papilloma developed breast cancers at the resection site of the papilloma, but
      none of these subsequent breast cancers had the PIK3CA mutation. These results
      indicate that a papilloma stems from a bipotent progenitor cell that contains the
      AKT1 or PIK3CA mutation and proliferates and differentiates to form the
      papilloma. Papilloma can be a risk factor for developing breast cancer but is
      unlikely to be its obligate precursor.

PMID- 29454755
TI  - Evaluation of antidiabetic potential of steroidal alkaloid of Sarcococca saligna.
AB  - The demand for natural medicines has increased because of their limited adverse
      effects. The aim of study is to explore the antidiabetic potential of isolated
      steroidal alkaloid from Sarcococca saligna in streptozotocin induced diabetic
      rats. To determine the antidiabetic activity of steroidal alkaloids, diabetes was
      induced in rats by injecting streptozotocin intraperitoneally at a dose of 40
      mg/Kg. After a week of STZ injection the treatment were started and the 8th day
      was considered as the 1st day of treatment and up to four weeks the rats were
      treated with steroidal alkaloids. Animals were divided into five groups, group 1
      considered as a control group by receiving normal saline (1 ml/Kg) twice daily
      and group 2, 3, 4 were treated with active compound sarcovagine-D, saracodine and
      holaphylline at the dose of 5 mg/Kg subcutaneously twice a day while group 5 was
      treated with a standard drug glibenclamide at a dose of 1 mg/Kg/day. The result
      showed that treated group 2 and 4 reduced the glucose level in blood
      significantly while group 3 showed moderate glucose reduction. The fructosamine
      level reduced significantly in treating group 4 from the 2nd week of treatment
      while group 2 and 3 decreased the level significantly in week 4 in diabetic rats.
      The treated groups showed gradual decreases the glucose level in 1st and 2nd week
      of oral glucose tolerance test compared to control group. The group receiving
      holaphylline (4) and sarcovagine-D (2) showed good improvements in blood lipids
      while the effect of compound on body weight showed less significant improvement.
      The present study concluded that steroid alkaloids from isolated Sarcococca
      saligna possess hypoglycemic effect and improve others diabetes associated
      complications. Together these finding further research is needed using a range of
      doses to explore the other possible beneficial effects in diabetes mellitus and
      its molecular mechanism.

PMID- 29454756
TI  - Outcomes after acute symptomatic seizures in neonates.
AB  - Acute symptomatic seizures are a common sign of neurological dysfunction and
      brain injury in neonates and occur in approximately one to three per 1000 live
      births. Seizures in neonates are usually a sign of underlying brain injury and,
      as such, are commonly associated with adverse outcomes. Neurological morbidities
      in survivors often co-occur; epilepsy, cerebral palsy, and intellectual
      disability often occur together in the most severely affected children. Risk
      factors for adverse outcome include prematurity, low Apgar scores, low pH on the
      first day of life, seizure onset <24 or >72 h after birth, abnormal neonatal
      neurological examination, abnormal neonatal electroencephalographic background,
      status epilepticus, and presence and pattern of brain injury (particularly deep
      gray or brainstem injury). Despite this list of potential indicators, accurate
      prediction of outcome in a given child remains challenging. There is great need
      for long-term, multicenter studies to examine risk factors for, and pathogenesis
      of, adverse outcomes following acute symptomatic seizures in neonates.

PMID- 29454757
TI  - Open Reduction and Internal Fixation of Mandibular Condylar Base and Neck
      Fractures Using Strut Plates.
AB  - PURPOSE: To evaluate clinical, radiologic, and functional outcomes of patients
      with condylar neck or base fractures treated with open reduction and internal
      fixation using strut plates. PATIENTS AND METHODS: Thirty patients with 34
      condylar neck and base fractures were included in the study. Transoral
      endoscopically assisted, submandibular, or transparotid approaches were
      performed. Clinical and radiologic outcomes were evaluated. Functional outcomes
      were assessed with the Helkimo index in a subgroup of 15 patients. RESULTS: Strut
      plates were successfully placed in all surgical approaches used in this study.
      Fracture healing occurred without complications in 33 condylar processes. One
      plate fracture occurred. In the subgroup, 7 patients had a good functional
      outcome, 7 had a slightly impaired functional outcome, and 1 patient had a
      moderately impaired functional outcome. CONCLUSION: Strut plates are appropriate
      for retromandibular transparotid, endoscopically assisted transoral, or
      submandibular approaches in the management of condylar neck or base fractures.
      Intraoperative handling and fitting accuracy of the strut plates are good. Good
      to slightly impaired functional outcome was observed in a subgroup of patients.

PMID- 29454758
TI  - Optical fiber tips for biological applications: From light confinement,
      biosensing to bioparticles manipulation.
AB  - BACKGROUND: The tip of an optical fiber has been considered an attractive
      platform in Biology. The simple cleaved end of an optical fiber can be machined,
      patterned and/or functionalized, acquiring unique properties enabling the
      exploitation of novel optical phenomena. Prompted by the constant need to measure
      and manipulate nanoparticles, the invention of the Scanning Near-field Optical
      Microscopy (SNOM) triggered the optimization and development of novel fiber tip
      microfabrication methods. In fact, the fiber tip was soon considered a key
      element in SNOM by confining light to sufficiently small extensions, challenging
      the diffraction limit. As result and in consequence of the newly proposed "Lab On
      Tip" concept, several geometries of fiber tips were applied in three main fields:
      imaging (in Microscopy/Spectroscopy), biosensors and micromanipulation (Optical
      Fiber Tweezers, OFTs). These are able to exert forces on microparticles, trap and
      manipulate them for relevant applications, as biomolecules mechanical study or
      protein aggregates unfolding. SCOPE OF REVIEW: This review presents an overview
      of the main achievements, most impactful studies and limitations of fiber tip
      based configurations within the above three fields, along the past 10 years.
      MAJOR CONCLUSIONS: OFTs could be in future a valuable tool for studying several
      cellular phenomena such as neurodegeneration caused by abnormal protein fibrils
      or manipulating organelles within cells. This could contribute to understand the
      mechanisms of some diseases or biophenomena, as the axonal growth in neurons.
      GENERAL SIGNIFICANCE: To the best of our knowledge, no other review article has
      so far provided such a broad view. Despite of the limitations, fiber tips have
      key roles in Biology/Medicine.

PMID- 29454759
TI  - Chromosomal numerical aberration pattern in papillary renal cell carcinoma:
      Review article.
AB  - Traditionally, papillary renal cell carcinomas (PRCCs) have been divided in two
      subgroups - type 1 and type 2. Based on recent molecular and genetic developments
      in the understanding of RCCs, it seems that this traditional classification may
      not be adequate and that the spectrum of PRCCs is much wider than initially
      proposed. Small series of distinct types of PRCC which do not fit into the above
      mentioned categories have been described in the literature. Published studies
      investigating molecular genetic changes in various types of PRCCs have shown that
      the molecular genetic features are remarkably heterogeneous across the whole
      spectrum of PRCCs. Of all PRCC subtypes/variants, PRCC type 1 seems to be a
      genetically uniform group, while other types showed different degrees of
      heterogeneity. Among different molecular-genetic features, chromosomal numerical
      aberration status is one of the most frequently studied features so far. It is
      becoming more evident that tumor type-specific chromosomal numerical aberration
      status in PRCCs may not exist. In this review, we present the most current
      knowledge concerning chromosomal numerical aberration status in PRCCs.

PMID- 29454760
TI  - Radiolabeled Duramycin: Promising Translational Imaging of Myocardial Apoptosis.

PMID- 29454761
TI  - Diagnostic Accuracy of Cardiovascular Magnetic Resonance in Acute Myocarditis: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: The purpose of this systematic review was to explore the diagnostic
      accuracy of various cardiovascular magnetic resonance (CMR) index tests for the
      diagnosis of acute myocarditis in adult patients. BACKGROUND: Acute myocarditis
      remains one of the most challenging diagnoses in cardiology. CMR has emerged as
      the diagnostic tool of choice to detect acute myocardial injury and necrosis in
      patients with suspected myocarditis. METHODS: We considered all diagnostic cohort
      and case-control studies. We searched MEDLINE, EMBASE, Cochrane Library, SCOPUS,
      and Web of Science up to April 21, 2017. We used the Quality Assessment of
      Diagnostic Accuracy Studies-2 tool to assess the quality of included studies.
      PROSPERO registration number CRD42017055778 was used. RESULTS: Twenty-two studies
      were included in the systematic review. Because significant heterogeneity exists
      among the studies, we only present hierarchical receiver operator curves. The
      areas under the curve (AUC) for each index test were for T1 mapping 0.95 (95%
      confidence interval [CI]: 0.93 to 0.97), for T2 mapping 0.88 (95% CI: 0.85 to
      0.91), for extracellular volume fraction (ECV) 0.81 (95% CI: 0.78 to 0.85), for
      increased T2 ratio/signal 0.80 (95% CI: 0.76 to 0.83), for late gadolinium
      enhancement (LGE) 0.87 (95% CI: 0.84 to 0.90), for early gadolinium enhancement
      (EGE) 0.78 (95% CI: 0.74 to 0.81), and for the Lake Louise criteria (LLC) 0.81
      (95% CI: 0.77 to 0.84). Native T1 mapping had superior diagnostic accuracy across
      all index tests. The AUC of T2 mapping was greater than the AUC of increased T2
      ratio/signal and EGE, whereas ECV showed no superiority compared with other index
      tests. LGE had better diagnostic accuracy compared with the classic CMR index
      tests, similar accuracy with T2 mapping and ECV, and only T1 mapping surpassed
      it. CONCLUSIONS: Novel CMR mapping techniques provide high diagnostic accuracies
      for the diagnosis of acute myocarditis and constitute promising successors of the
      classic elements of the LLC for routine diagnostic protocols.

PMID- 29454762
TI  - Prognostic Value of Right Ventricular Dysfunction on Clinical Outcomes After
      Transcatheter Aortic Valve Replacement.
AB  - OBJECTIVES: The purpose of this study was to investigate the association between
      right ventricular dysfunction (RVD) and cardiovascular death after transcatheter
      aortic valve replacement (TAVR). BACKGROUND: There is conflicting evidence on the
      effect of RVD on clinical outcomes after TAVR. METHODS: A total of 1,116 TAVR
      patients (age 82 +/- 6 years; 51% female) who were consecutively enrolled into a
      prospective registry underwent detailed pre-operative assessment of right
      ventricular (RV) function and were dichotomized into 2 groups for the purposes of
      the present retrospective analysis. RVD was assessed using fractional area change
      (<35%), tricuspid annular plane systolic excursion (<1.7 cm), and systolic
      movement of the RV lateral wall by tissue Doppler imaging (<9.5 cm/s). RVD was
      found in 325 (29.1%) patients. The primary outcome was cardiovascular death at 1
      year. RESULTS: After adjustment for comorbidities, patients with RVD had a higher
      risk of cardiovascular death at 1 year compared with patients with normal RV
      function (20.1% vs. 7.1%; adjusted hazard ratio [HRadj]: 2.94; 95% confidence
      interval [CI]: 2.02 to 4.27; p < 0.001). The difference emerged within the first
      30 days after TAVR (9.0% vs. 2.2%; HRadj: 4.62; 95% CI: 2.51 to 8.50; p < 0.001).
      Normalization of RV function after TAVR was found in 57.4% of patients with RVD
      at baseline. There was a gradient of increasing risk of cardiovascular death
      among patients with normal RV function, RVD recovery (HRadj: 2.16; 95% CI: 1.16
      to 4.02), new RVD (HRadj: 3.93; 95% CI: 2.09 to 7.39), and maintained RVD (HRadj:
      8.74; 95% CI: 5.33 to 14.3), respectively. CONCLUSIONS: RVD at baseline was
      associated with a more than 2-fold increased risk of cardiovascular death at 1
      year after TAVR, with a gradient of risk according to RVD recovery. (Swiss TAVI
      Registry; NCT01368250).

PMID- 29454763
TI  - Early Strut Coverage in Patients Receiving Drug-Eluting Stents and its
      Implications for Dual Antiplatelet Therapy: A Randomized Trial.
AB  - OBJECTIVES: This study sought to measure early strut coverage in patients
      receiving drug-eluting stents (DESs) and to explore the feasibility of short-term
      dual antiplatelet therapy (DAPT) based on the degree of early strut coverage.
      BACKGROUND: Data for early strut coverage in patients receiving new-generation
      DESs, and its implications for DAPT continuation were limited. METHODS: A
      randomized, multicenter trial was conducted in 894 patients treated with DESs.
      Patients were randomly assigned to everolimus-eluting stent (EES) (n = 444) or
      biolimus-eluting stent (BES) (n = 450) groups and optical coherence tomography
      (OCT)-guided (n = 445) or angiography-guided (n = 449) implantation groups using
      a 2-by-2 factorial design. Early strut coverage was measured as the percentage of
      uncovered struts on 3-month follow-up OCT examination. The primary outcome was
      the difference in early strut coverage between EES and BES groups and between OCT
      and angiography-guided implantation groups. The secondary outcome was a
      composite of cardiac death, myocardial infarction, stent thrombosis, and major
      bleeding during the first 12 months post-procedure in patients receiving 3-month
      DAPT based on the presence of early strut coverage (<=6% uncovered) on 3-month
      follow-up OCT. RESULTS: Three-month follow-up OCT data were acquired for 779
      patients (87.1%). The median percentage of uncovered struts at 3 months was 8.9%
      and 8.2% in the EES and BES groups, respectively (p = 0.69) and was lower in the
      OCT-guided group (7.5%) than in the angiography-guided group (9.9%; p = 0.009).
      Favorable early strut coverage (<=6% uncovered strut) was observed in 320 of 779
      patients (41.1%). At 12 months, the composite event rarely occurred in the 3
      month (0.3%) or 12-month (0.2%) DAPT groups (p = 0.80). CONCLUSIONS: OCT-guided
      DES implantation improved early strut coverage compared with angiography-guided
      DES implantation, with no difference in strut coverage between EES and BES
      groups. Short-term DAPT may be feasible in selected patients with favorable early
      strut coverage (Determination of the Duration of the Dual Antiplatelet Therapy by
      the Degree of the Coverage of The Struts on Optical Coherence Tomography From the
      Randomized Comparison Between Everolimus-eluting Stents Versus Biolimus A9
      eluting Stents [DETECT-OCT]; NCT01752894).

PMID- 29454764
TI  - Importance of Sex-Specific Regression Models to Estimate Synthetic Hematocrit and
      Extracellular Volume Fraction.

PMID- 29454765
TI  - Thrombus-Related Coronary High-Intensity Signal on T1-Weighted Magnetic Resonance
      Imaging Is a Potential Predictor of Adverse Cardiovascular Events After Stent
      Implantation.

PMID- 29454766
TI  - Molecular Imaging of Apoptosis in Cancer Therapy-Related Cardiac Dysfunction
      Before LVEF Reduction.

PMID- 29454767
TI  - Diagnostic Performance of Fully Automated Pixel-Wise Quantitative Myocardial
      Perfusion Imaging by Cardiovascular Magnetic Resonance.
AB  - OBJECTIVES: The authors developed a fully automated framework to quantify
      myocardial blood flow (MBF) from contrast-enhanced cardiac magnetic resonance
      (CMR) perfusion imaging and evaluated its diagnostic performance in patients.
      BACKGROUND: Fully quantitative CMR perfusion pixel maps were previously validated
      with microsphere MBF measurements and showed potential in clinical applications,
      but the methods required laborious manual processes and were excessively time
      consuming. METHODS: CMR perfusion imaging was performed on 80 patients with known
      or suspected coronary artery disease (CAD) and 17 healthy volunteers. Significant
      CAD was defined by quantitative coronary angiography (QCA) as >=70% stenosis.
      Nonsignificant CAD was defined by: 1) QCA as <70% stenosis; or 2) coronary
      computed tomography angiography as <30% stenosis and a calcium score of 0 in all
      vessels. Automatically generated MBF maps were compared with manual
      quantification on healthy volunteers. Diagnostic performance of the automated MBF
      pixel maps was analyzed on patients using absolute MBF, myocardial perfusion
      reserve (MPR), and relative measurements of MBF and MPR. RESULTS: The correlation
      between automated and manual quantification was excellent (r = 0.96). Stress MBF
      and MPR in the ischemic zone were lower than those in the remote myocardium in
      patients with significant CAD (both p < 0.001). Stress MBF and MPR in the remote
      zone of the patients were lower than those in the normal volunteers (both p <
      0.001). All quantitative metrics had good area under the curve (0.864 to 0.926),
      sensitivity (82.9% to 91.4%), and specificity (75.6% to 91.1%) on per-patient
      analysis. On a per-vessel analysis of the quantitative metrics, area under the
      curve (0.837 to 0.864), sensitivity (75.0% to 82.7%), and specificity (71.8% to
      80.9%) were good. CONCLUSIONS: Fully quantitative CMR MBF pixel maps can be
      generated automatically, and the results agree well with manual quantification.
      These methods can discriminate regional perfusion variations and have high
      diagnostic performance for detecting significant CAD. (Technical Development of
      Cardiovascular Magnetic Resonance Imaging; NCT00027170).

PMID- 29454768
TI  - The Dilemma of Exertional Dyspnea and Diagnosis of Heart Failure: Convergent and
      Discriminant Validity.

PMID- 29454769
TI  - CMR Mapping for Myocarditis: Coming Soon to a Center Near You.

PMID- 29454771
TI  - Incremental Benefit of CT Perfusion to CT Coronary Angiography: Another Step to
      the One-Stop-Shop?

PMID- 29454770
TI  - Molecular Imaging of Apoptosis in Ischemia Reperfusion Injury With Radiolabeled
      Duramycin Targeting Phosphatidylethanolamine: Effective Target Uptake and Reduced
      Nontarget Organ Radiation Burden.
AB  - OBJECTIVES: The purpose of this study was to evaluate the feasibility of imaging
      apoptosis in experimental ischemia-reperfusion model by technetium-99m (99mTc)
      labeled Duramycin, and compare it to an established tracer, 99mTc-labeled Annexin
      V, which has a relative disadvantage of high radiation burden to nontarget
      organs. BACKGROUND: During apoptosis, the cell membrane phospholipids
      phosphatidylserine (PS) and phosphatidylethanolamine (PE) are exposed and can be
      targeted by Annexin-V and Duramycin, respectively, for in vivo imaging.
      Identification of a reversible cell death process should permit therapeutic
      intervention to help reduce myocyte loss and left ventricle dysfunction. METHODS:
      In a 40-min left coronary artery ischemia-reperfusion model in 17 rabbits, 7 mCi
      of 99mTc-labeled Duramycin (n = 10), 99mTc-linear Duramycin (a negative tracer
      control; n = 3), or 99mTc-Annexin-V (a positive tracer-control; n = 4) were
      intravenously administered 30 min after reperfusion. Of the 10 Duramycin group
      animals, 4 animals were treated with an antiapoptotic agent, minocycline at the
      time of reperfusion. In vivo and ex vivo micro-single-photon emission computed
      tomography (MUSPECT) and micro-computed tomography (MUCT) imaging was performed 3
      h after reperfusion, followed by quantitative assessment of tracer uptake and
      pathological characterization. Fluorescent Duramycin and Annexin-V were injected
      in 4 rats to visualize colocalization in infarct areas in a 40-min left coronary
      artery occlusion and 30-min reperfusion model. RESULTS: Intense uptake of
      Duramycin and Annexin-V was observed in the apical (infarcted) areas. The percent
      injected dose per gram uptake of Duramycin in apical region (0.751 +/- 0.262%)
      was significantly higher than remote area in same animals (0.045 +/- 0.029%; p <
      0.01). Duramycin uptake was insignificantly lower than Annexin-V uptake (1.23 +/-
      0.304%; p > 0.01) but demonstrated substantially lower radiation burden to
      kidneys (0.358 +/- 0.210% vs. 1.58 +/- 0.316%, respectively; p < 0.001).
      Fluorescence studies with Duramycin and Annexin V showed colocalization in
      infarct areas. Minocycline treatment substantially resolved Duramycin uptake
      (0.354% +/- 0.0624%; p < 0.01). CONCLUSIONS: Duramycin is similarly effective in
      imaging apoptotic cell death as Annexin-V with lower nontarget organ radiation.
      Clinical feasibility of apoptosis imaging with a PE-seeking tracer should be
      tested.

PMID- 29454772
TI  - Decreased Exercise Tolerance in Stage B Heart Failure: A Shade of Grey.

PMID- 29454773
TI  - Relationship Between Left Atrial Functional Measures and Incident Atrial
      Fibrillation in the General Population: The Copenhagen City Heart Study.
AB  - OBJECTIVES: This study sought to investigate whether left atrial (LA) functional
      measures predict atrial fibrillation (AF) in the general population. BACKGROUND:
      Increasing evidence suggests LA functional measures are predictors of AF in
      several patient groups. METHODS: In a community-based cohort study, approximately
      2,000 individuals underwent a transthoracic echocardiogram. Conventional
      echocardiographic measures and extended LA measures, including the minimal and
      maximal LA volumes (LAVmin and LAVmax, respectively) and left atrial emptying
      fraction (LAEF), were performed. The endpoint was incident AF, and participants
      with known AF were excluded, which left 1,951 for inclusion. RESULTS: Over 11.0
      years of follow-up, 184 (9.4%) developed AF. Those who developed AF had
      significantly larger LA volumes and lower LAEF than participants free of AF.
      These LA measures were univariable predictors of AF (LAVmax hazard ratio [HR]:
      1.10 [95% confidence interval (CI): 1.08 to 1.12] per 1-ml increase, p < 0.001;
      LAVmin HR: 1.14 [95% CI: 1.12 to 1.16] per 1-ml increase, p < 0.001; LAEF HR:
      1.03 [95% CI: 1.02 to 1.04] per percent decrease, p < 0.001). All LA measures
      remained predictors independent of clinical risk scores, with LAVmin providing
      the highest C-statistics when added to these risk scores (C-statistic for CHADS2
      0.728 vs. CHADS2 + LAVmin 0.778; C-statistic for CHARGE-AF 0.815 vs. CHARGE-AF +
      LAVmin 0.830). However, hypertension modified the relationship between the
      measures of LA function (both LAVmin and LAEF) and risk of AF (p for interaction
      < 0.001), which was not the case for LAVmax (p = 0.22). The measures of LA
      function mainly provided prognostic information regarding risk of AF in
      participants without hypertension. Even when we restricted our analysis to
      individuals without hypertension and nondilated LA (LAVmax<34 ml/m2), the LAVmin
      and LAEF remained significantly independent predictors of AF after multivariable
      adjustments (LAVmin HR: 1.12 [95% CI: 1.01 to 1.24], p = 0.028, and LAEF HR: 1.03
      [95% CI: 1.00 to 1.06], p = 0.021, respectively). CONCLUSIONS: LA functional
      measures predict AF in the general population and provide prognostic information
      incremental to clinical risk scores. In individuals without hypertension and
      nondilated LA, these measures indicate an increased risk of AF.

PMID- 29454775
TI  - Left Ventricular Dysfunction and Exercise Capacity Trajectory: Implications for
      Subclinical Heart Failure Staging Criteria.
AB  - OBJECTIVES: This study aimed to determine the association of stage B heart
      failure (SBHF) and its constituent left ventricular (LV) abnormalities with
      trajectory of exercise capacity over time, and assess whether this association is
      modified by reversion of these LV abnormalities to normal. BACKGROUND: The LV
      abnormalities of SBHF may coincide with a reduction in exercise capacity that
      precedes the overt exercise intolerance of clinical heart failure (HF).
      Determining the predictive capacity of established and novel SBHF criteria for
      exercise capacity decline may improve HF risk stratification. METHODS: LV
      structure/function (echocardiography) and exercise capacity (6-minute walk
      distance [6MWD]) were assessed at baseline and 3-year follow-up in 268 patients
      from the NIL-CHF (Nurse-led Intervention for Less Chronic Heart Failure) study
      (all stage A [SAHF] or SBHF). Changes (Delta) in 6MWD were compared between SAHF
      and SBHF and across each of 4 constituent components of SBHF: LV hypertrophy,
      regional wall motion abnormality(ies) (RWMA), left ventricular systolic
      dysfunction (LVSD) (ejection fraction <45%) and elevated early diastolic
      filling/annular velocity ratio (E/e' >= 15). RESULTS: Delta6MWD was similar in
      those with SAHF (n = 141) and SBHF (n = 127; -5 m [95% confidence interval (CI): 
      21 to +11 m]; covariate-adjusted). However, within the setting of SBHF there was
      substantive heterogeneity; that is, reductions in 6MWD were observed with
      persistent elevated E/e' (-34 m [95% CI: -62 to -6 m]) and persistent LVSD (-41 m
      [95% CI: -74 to -8 m]), but not with LV hypertrophy (+17 m [95% CI: -15 to +49 m)
      or RWMA (+5 m [-27 to +36 m]), nor in patients whose elevated E/e' or LVSD
      reverted to normal by 3 years (p > 0.10). CONCLUSIONS: Elevated E/e' is
      associated with a similar degree of exercise capacity decline to LVSD, supporting
      that both LV functional criteria be considered in distinguishing SBHF from SAHF.
      That reversion of either manifestation of LV dysfunction was associated with
      preserved exercise capacity advocates targeting of these factors by HF preventive
      interventions.

PMID- 29454774
TI  - Incremental Diagnostic Value of Stress Computed Tomography Myocardial Perfusion
      With Whole-Heart Coverage CT Scanner in Intermediate- to High-Risk Symptomatic
      Patients Suspected of Coronary Artery Disease.
AB  - OBJECTIVES: The goal of this study was to evaluate the diagnostic accuracy of
      stress computed tomography myocardial perfusion (CTP) for the detection of
      functionally significant coronary artery disease (CAD) by using invasive coronary
      angiography (ICA) plus invasive fractional flow reserve (FFR) as the reference
      standard in consecutive intermediate- to high-risk symptomatic patients.
      BACKGROUND: Stress CTP recently emerged as a potential strategy to combine the
      anatomic and functional evaluation of CAD in a single scan. METHODS: A total of
      100 consecutive symptomatic patients scheduled for ICA were prospectively
      enrolled. All patients underwent rest coronary computed tomography angiography
      (CTA) followed by stress static CTP with a whole-heart coverage CT scanner
      (Revolution CT, GE Healthcare, Milwaukee, Wisconsin). Diagnostic accuracy and
      overall effective dose were assessed and compared versus those of ICA and
      invasive FFR. RESULTS: The prevalence of obstructive CAD and functionally
      significant CAD were 69% and 44%, respectively. Coronary CTA alone demonstrated a
      per-vessel and per-patient sensitivity, specificity, negative predictive value,
      positive predictive value, and accuracy of 98%, 76%, 99%, 63%, and 83% and of
      98%, 54%, 96%, 68%, and 76%, respectively. Combining coronary CTA with stress
      CTP, per-vessel and per-patient sensitivity, specificity, negative predictive
      value, positive predictive value, and accuracy were 91%, 94%, 96%, 86%, and 93%
      and 98%, 83%, 98%, 86%, and 91%, with a significant improvement in specificity,
      positive predictive value, and accuracy in both models. The mean effective dose
      for coronary CTA and stress CTP were 2.8 +/- 1.4 mSv and 2.5 +/- 1.1 mSv.
      CONCLUSIONS: The inclusion of stress CTP for the evaluation of patients with an
      intermediate to high risk for CAD is feasible and improved the diagnostic
      performance of coronary CTA for detecting functionally significant CAD.

PMID- 29454776
TI  - Cardiac Magnetic Resonance Myocardial Feature Tracking for Optimized Prediction
      of Cardiovascular Events Following Myocardial Infarction.
AB  - OBJECTIVES: The aims of the study were to assess the prognostic significance of
      cardiac magnetic resonance myocardial feature tracking (CMR-FT) in a large
      multicenter study and to evaluate the most potent CMR-FT predictor of hard
      clinical events following myocardial infarction (MI). BACKGROUND: CMR-FT is a new
      method that allows accurate assessment of global and regional circumferential,
      radial, and longitudinal myocardial strain. The prognostic value of CMR-FT in
      patients with reperfused MI is unknown. METHODS: The study included 1,235 MI
      patients (n = 795 with ST-segment elevation MI and 440 with non-ST-elevation MI)
      at 15 centers. All patients were reperfused by primary percutaneous coronary
      intervention. Central core laboratory-masked analyses were performed to determine
      left ventricular (LV) circumferential, radial, and longitudinal strain. The
      primary clinical endpoint of the study was the occurrence of major adverse
      cardiac events within 12 months after infarction. RESULTS: Patients with
      cardiovascular events had significantly impaired CMR-FT strain values (p < 0.001
      for all). Global longitudinal strain was identified as the strongest CMR-FT
      parameter of future cardiovascular events and emerged as an independent predictor
      of poor prognosis following MI even after adjustment for established prognostic
      markers. Global longitudinal strain provided an incremental prognostic value for
      all-cause mortality above LV ejection fraction (c-index increase from 0.65 to
      0.73; p = 0.04) and infarct size (c-index increase from 0.60 to 0.78; p = 0.002).
      CONCLUSIONS: CMR-FT is a superior measure of LV function and performance early
      after reperfused MI with incremental prognostic value for mortality over and
      above LV ejection fraction and infarct size. (Abciximab i.v. Versus i.c. in ST
      segment elevation Myocardial Infarction [AIDA STEMI]; NCT00712101; Thrombus
      Aspiration in ThrOmbus Containing culpRIT Lesions in Non-ST-Elevation Myocardial
      Infarction [TATORT-NSTEMI]; NCT01612312).

PMID- 29454777
TI  - Undiluted Contrast Media in the Pulmonary Veins and Left Atrium After
      Cavopulmonary Connection: CT Sign of a Right-to-Left Shunt.

PMID- 29454778
TI  - Computed Tomography for Diagnosis and Classification of Bicuspid Aortic Valve
      Disease in Transcatheter Aortic Valve Replacement.

PMID- 29454779
TI  - Effect of Traditional Heart Failure Risk Factors on Myocardial Dysfunction in
      Adult Survivors of Childhood Cancer.

PMID- 29454780
TI  - Infective Endocarditis After Bentall Surgery: Usefulness of New Imaging
      Modalities and Outcomes.

PMID- 29454781
TI  - Imaging of C-X-C Motif Chemokine Receptor CXCR4 Expression After Myocardial
      Infarction With [68Ga]Pentixafor-PET/CT in Correlation With Cardiac MRI.

PMID- 29454782
TI  - Global Left Atrial Strain as a Predictor of Silent Atrial Fibrillation Following
      Dual Chamber Cardiac Implantable Electronic Device Implantation.

PMID- 29454783
TI  - Comparison of the Diastolic Stress Test With a Combined Resting Echocardiography
      and Biomarker Approach to Patients With Exertional Dyspnea: Diagnostic and
      Prognostic Implications.
AB  - OBJECTIVES: This study sought to establish the diagnostic and prognostic value of
      a strategy for prediction of abnormal diastolic response to exercise (AbnDR)
      using clinical, biochemical, and resting echocardiographic markers in dyspneic
      patients with mild diastolic dysfunction. BACKGROUND: An AbnDR (increase in left
      ventricular filling pressure) may indicate heart failure with preserved ejection
      fraction as the cause of symptoms in dyspneic patients, despite a nonelevated
      noncardiac at rest. However, exercise testing may be inconclusive in patients
      with noncardiac limitations to physical activity. METHODS: In 171 dyspneic
      patients (64 +/- 8 years) with suspected heart failure with preserved ejection
      fraction but resting peak early diastolic mitral inflow velocity/peak early
      diastolic mitral annular velocity ratio (E/e') <14, a complete echocardiogram
      (including assessment of myocardial deformation and rotational mechanics) and
      blood assays for biomarkers were performed. Echocardiography following maximal
      exercise was undertaken to assess AbnDR (exertional E/e' >14). Patients were
      followed over 26.2 +/- 4.6 months for endpoints of cardiovascular hospitalization
      and death. RESULTS: AbnDR was present in 103 subjects (60%). Independent
      correlates of AbnDR were resting E/e' (odds ratio [OR]: 8.23; 95% confidence
      interval [CI]: 3.54 to 9.16; p < 0.001), left ventricular untwisting rate (OR:
      0.60; 95% CI: 0.42 to 0.86; p = 0.006), and galectin-3-a marker of fibrosis (OR:
      1.80; 95% CI: 1.21 to 2.67; p = 0.004). The use of resting E/e' >11.3 and
      galectin-3 <1.17 ng/ml to select patients for further diagnostic processing would
      have allowed exercise testing to be avoided in 65% of subjects, at the cost of
      misclassification of 13%. The composite outcome of cardiovascular hospitalization
      or death occurred in 47 patients (27.5%). The predictive value of an AbnDR
      response and the combined strategy (resting echocardiography and galectin-3 or
      exercise testing in case of an inconclusive first step) showed similar event
      prediction (36 vs. 34; p = 0.95). CONCLUSIONS: The implementation of a 2-step
      algorithm (echocardiographic evaluation of resting E/e' followed by the
      assessment of galectin-3) may improve the diagnosis and prognostic assessment of
      individuals with suspected heart failure with preserved ejection fraction who are
      unable to perform a diagnostic exercise test.

PMID- 29454784
TI  - Coronary Artery Calcium Scores and Atherosclerotic Cardiovascular Disease Risk
      Stratification in Smokers: MESA.
AB  - OBJECTIVES: This study assessed the utility of the pooled cohort equation (PCE)
      and/or coronary artery calcium (CAC) for atherosclerotic cardiovascular disease
      (ASCVD) risk assessment in smokers, especially those who were lung cancer
      screening eligible (LCSE). BACKGROUND: The U.S. Preventive Services Task Force
      recommended and the Centers for Medicare & Medicaid Services currently pays for
      annual screening for lung cancer with low-dose computed tomography scans in a
      specified group of cigarette smokers. CAC can be obtained from these low-dose
      scans. The incremental utility of CAC for ASCVD risk stratification remains
      unclear in this high-risk group. METHODS: Of 6,814 MESA (Multi-Ethnic Study of
      Atherosclerosis) participants, 3,356 (49.2% of total cohort) were smokers (2,476
      former and 880 current), and 14.3% were LCSE. Kaplan-Meier, Cox proportional
      hazards, area under the curve, and net reclassification improvement (NRI)
      analyses were used to assess the association between PCE and/or CAC and incident
      ASCVD. Incident ASCVD was defined as coronary death, nonfatal myocardial
      infarction, or fatal or nonfatal stroke. RESULTS: Smokers had a mean age of 62.1
      years, 43.5% were female, and all had a mean of 23.0 pack-years of smoking. The
      LCSE sample had a mean age of 65.3 years, 39.1% were female, and all had a mean
      of 56.7 pack-years of smoking. After a mean of 11.1 years of follow-up 13.4% of
      all smokers and 20.8% of LCSE smokers had ASCVD events; 6.7% of all smokers and
      14.2% of LCSE smokers with CAC = 0 had an ASCVD event during the follow-up. One
      SD increase in the PCE 10-year risk was associated with a 68% increase risk for
      ASCVD events in all smokers (hazard ratio: 1.68; 95% confidence interval: 1.57 to
      1.80) and a 22% increase in risk for ASCVD events in the LCSE smokers (hazard
      ratio: 1.22; 95% confidence interval: 1.00 to 1.47). CAC was associated with
      increased ASCVD risk in all smokers and in LCSE smokers in all the Cox models.
      The C-statistic of the PCE for ASCVD was higher in all smokers compared with LCSE
      smokers (0.693 vs. 0.545). CAC significantly improved the C-statistics of the PCE
      in all smokers but not in LCSE smokers. The event and nonevent net
      reclassification improvements for all smokers and LCSE smokers were 0.018 and 
      0.126 versus 0.16 and -0.196, respectively. CONCLUSIONS: In this well
      characterized, multiethnic U.S. cohort, CAC was predictive of ASCVD in all
      smokers and in LCSE smokers but modestly improved discrimination over and beyond
      the PCE. However, 6.7% of all smokers and 14.2% of LCSE smokers with CAC = 0 had
      an ASCVD event during follow-up.

PMID- 29454786
TI  - Rhinovirus respiratory tract infection in hospitalized adult patients is
      associated with TH2 response irrespective of asthma.
AB  - OBJECTIVES: We assessed the immunological response of hospitalized adult patients
      with rhinovirus infection, including critically-ill patients. METHODS: The
      differential white blood cell (WBC) count and the levels of 29 plasma
      cytokines/chemokines were compared between 50 adult hospitalized patients with
      rhinovirus infection and 100 age-matched controls with influenza virus infection.
      RESULTS: The demographics and comorbidities were similar between rhinovirus and
      influenza patients, but severe disease was more common for the rhinovirus cohort.
      Rhinovirus patients had significantly higher WBC counts than influenza patients,
      especially for eosinophil (P = 3.1 * 10-8). The level of the TH2 cytokine IL-5
      was significantly higher among rhinovirus patients, while the levels of 9 other
      cytokines/chemokines were significantly lower among rhinovirus patients. The
      levels of CXCL-10 (IP-10), CCL-2 (MCP-1), IFN-alpha2, IFN-gamma, IL-10, and IL-15
      remained significantly lower among rhinovirus patients after correction for
      multiple comparisons. Notably, CXCL-10 had the highest area under the receiver
      operating characteristic curve (AUC) in differentiating rhinovirus from influenza
      patients (AUC, 0.918). In the patient subgroup without asthma, the difference in
      the WBC count and cytokine/chemokine levels between rhinovirus and influenza
      patients remained statistically significant. CONCLUSIONS: Rhinovirus infection
      was characterized by a prominent TH2 response, even in patients without asthma.
      CXCL-10 (IP-10) is a potential biomarker in differentiating rhinovirus from
      influenza infection.

PMID- 29454785
TI  - Lymphoid tissue inducer-A divergent member of the ILC family.
AB  - Innate lymphoid cells (ILCs) that are capable of producing effector cytokines
      reminiscent of CD4+ T helper (Th) cells during infections and tissue
      inflammations have drawn much attention in the immunology field in recent years.
      Within the ILCs, the lymphoid tissue inducer (LTi) cells that play a critical
      role in lymphoid organogenesis were identified long before the establishment of
      the ILC concept. LTi cells, developed and functioning mainly at the fetal stage,
      and LTi-like cells, presumably generated during the adulthood, are regarded as a
      subset of type 3 ILCs (ILC3s) because they express the ILC3 lineage-defining
      transcription factor RORgammat, and like other ILC3s, can produce an ILC3
      signature cytokine IL-22 and initiate protective immune responses against
      extracellular bacteria. However, LTi/LTi-like cells have a unique gene expression
      pattern, and they develop from a progenitor that is distinct from the progenitor
      of all other ILCs and the progenitor of conventional natural killer (cNK) cells.
      There are also several other unique features of LTi/LTi-like cells comparing to
      non-LTi ILC3s. In addition to their classical function in lymphoid organogenesis,
      LTi/LTi-like cells also have specialized functions in association with the
      adaptive immune system, which include their effects on T and B cell development,
      activation and function. In this review, we summarize these specific features of
      LTi/LTi-like cells and propose that these cells should be considered as a
      separated innate lymphoid lineage in parallel with other non-LTi ILCs and cNK
      cells.

PMID- 29454788
TI  - Advances and Challenges in Endoscopic Training.
AB  - One of the challenges of the current era is ensuring that endoscopic training is
      accomplished effectively in the face of multiple competing demands. As health
      care delivery evolves, with rising patient complexity and increasing productivity
      requirements, there is mounting pressure on the time available for training in
      the clinical setting. The practice of endoscopy itself continues to expand to
      include increasingly complex procedures (eg, therapeutic endoscopic ultrasound,
      endoscopic submucosal dissection, and peroral endoscopic myotomy) that require
      dedicated endoscopy training. The rapid pace of progress in the field of
      endoscopy means that the demand for endoscopy training is not limited to the
      formal period of training, but instead spans the spectrum to include physicians
      already in practice. In light of recent advances in our understanding of
      endoscopy training, this review will serve to highlight the current state of
      affairs with respect to endoscopic training and how we can consider approaching
      these challenges.

PMID- 29454787
TI  - Trans-envelope multidrug efflux pumps of Gram-negative bacteria and their
      synergism with the outer membrane barrier.
AB  - Antibiotic resistance is a serious threat to public health. Significant efforts
      are currently directed toward containment of the spread of resistance, finding
      new therapeutic options concerning resistant human and animal pathogens, and
      addressing the gaps in the fundamental understanding of mechanisms of resistance.
      Experimental data and kinetic modeling revealed a major factor in resistance, the
      synergy between active efflux and the low permeability barrier of the outer
      membrane, which dramatically reduces the intracellular accumulation of many
      antibiotics. The structural and mechanistic particularities of trans-envelope
      efflux pumps amplify the effectiveness of cell envelopes as permeability
      barriers. An important feature of this synergism is that efflux pumps and the
      outer membrane barriers are mechanistically independent and select antibiotics
      based on different physicochemical properties. The synergism amplifies even weak
      polyspecificity of multidrug efflux pumps and creates a major hurdle in the
      discovery and development of new therapeutics against Gram-negative pathogens.

PMID- 29454789
TI  - Less Is More: A Minimalist Approach to Endoscopy.
AB  - A substantial literature documents inappropriate usage of gastrointestinal
      endoscopy in a variety of clinical settings. Overusage of endoscopy appears to be
      common, and 30% or more of procedures performed in some clinical settings have
      questionable indications. The potential reasons for overuse of endoscopy are
      multiple, and include cancer phobia, fear of medical malpractice litigation,
      profit motive, the investigation of "incidentalomas" found on other imaging, and
      underappreciation of the delayed harms of endoscopy, among other reasons.
      Clinical guidelines, which should limit overuse of endoscopy, may instead serve
      to promote it, if authors opt to be "conservative," recommending endoscopy in
      situations of unclear utility. Several strategies may decrease overuse of
      endoscopy, including careful attention to risk stratification when choosing
      patients to screen, adherence to guidelines for surveillance intervals for
      colonoscopy, the use of quality indicators to identify outliers in endoscopy
      utilization, and education on appropriate indications and the risks of overuse at
      the medical student, residency, and fellowship levels.

PMID- 29454790
TI  - Super-Enhancer-Driven Long Non-Coding RNA LINC01503, Regulated by TP63, Is Over
      Expressed and Oncogenic in Squamous Cell Carcinoma.
AB  - BACKGROUND & AIMS: Long non-coding RNAs (lncRNAs) are expressed in tissue
      specific pattern, but it is not clear how these are regulated. We aimed to
      identify squamous cell carcinoma (SCC)-specific lncRNAs and investigate
      mechanisms that control their expression and function. METHODS: We studied
      expression patterns and functions of 4 SCC-specific lncRNAs. We obtained 113
      esophageal SCC (ESCC) and matched non-tumor esophageal tissues from a hospital in
      Shantou City, China, and performed quantitative reverse transcription polymerase
      chain reaction assays to measure expression levels of LINC01503. We collected
      clinical data from patients and compared expression levels with survival times.
      LINC01503 was knocked down using small interfering RNAs and oligonucleotides in
      TE7, TE5, and KYSE510 cell lines and overexpressed in KYSE30 cells. Cells were
      analyzed by chromatin immunoprecipitation sequencing, luciferase reporter assays,
      colony formation, migration and invasion, and mass spectrometry analyses. Cells
      were injected into nude mice and growth of xenograft tumors was measured.
      LINC01503 interaction with proteins was studied using fluorescence in situ
      hybridization, RNA pulldown, and RNA immunoprecipitation analyses. RESULTS: We
      identified a lncRNA, LINC01503, which is regulated by a super enhancer and is
      expressed at significantly higher levels in esophageal and head and neck SCCs
      than in non-tumor tissues. High levels in SCCs correlated with shorter survival
      times of patients. The transcription factor TP63 bound to the super enhancer at
      the LINC01503 locus and activated its transcription. Expression of LINC01503 in
      ESCC cell lines increased their proliferation, colony formation, migration, and
      invasion. Knockdown of LINC01503 in SCC cells reduced their proliferation, colony
      formation, migration, and invasion, and the growth of xenograft tumors in nude
      mice. Expression of LINC01503 in ESCC cell lines reduced ERK2 dephosphorylation
      by DUSP6, leading to activation of ERK signaling via MAPK. LINC01503 disrupted
      the interaction between EBP1 and the p85 subunit of PI3K, increasing AKT
      signaling. CONCLUSIONS: We identified an lncRNA, LINC01503, which is increased in
      SCC cells compared with non-tumor cells. Increased expression of LINC01503
      promotes ESCC cell proliferation, migration, invasion, and growth of xenograft
      tumors. It might be developed as a biomarker of aggressive SCCs in patients.

PMID- 29454791
TI  - Endoscopic Management of Transmural Defects, Including Leaks, Perforations, and
      Fistulae.
AB  - Transmural defects of the gastrointestinal tract can be classified into 3
      distinct entities-leak, perforation, and fistula. Each arises from different
      mechanisms and is managed accordingly. Leaks occur most often after surgery,
      while perforations occur most often after flexible endoscopic maneuvers. Fistulae
      arise from a variety of mechanisms, such as an evolution from surgical leaks, as
      well as from specific disease states. Endoscopic management plays a vital role in
      the treatment of transmural defects as long as the region of interest can be
      accessed with the appropriate endoscopic accessories. Endoscopic approaches can
      be broadly classified into those that provide closure and those that provide
      diversion of luminal contents. With advances in technology, a myriad of devices
      and accessories are available that allow a tailored approach. Endoscopic
      approaches to leaks, perforations, and fistulae are discussed in this review.

PMID- 29454792
TI  - Clinical and Genomic Correlates of Neutrophil Reactive Oxygen Species Production
      in Pediatric Patients With Crohn's Disease.
AB  - BACKGROUND & AIMS: Individuals with monogenic disorders of phagocyte function
      develop chronic colitis that resembles Crohn's disease (CD). We tested for
      associations between mutations in genes encoding reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidases, neutrophil function, and phenotypes of
      CD in pediatric patients. METHODS: We performed whole-exome sequence analysis to
      identify mutations in genes encoding NADPH oxidases (such as CYBA, CYBB, NCF1,
      NCF2, NCF4, RAC1, and RAC2) using DNA from 543 pediatric patients with
      inflammatory bowel diseases. Blood samples were collected from an additional 129
      pediatric patients with CD and 26 children without IBD (controls); we performed
      assays for neutrophil activation, reactive oxygen species (ROS) production, and
      bacteria uptake and killing. Whole-exome sequence analysis was performed using
      DNA from 46 of the children with CD to examine associations with NADPH gene
      mutations; RNA sequence analyses were performed using blood cells from 46
      children with CD to test for variations in neutrophil gene expression associated
      with ROS production. RESULTS: We identified 26 missense mutations in CYBA, CYBB,
      NCF1, NCF2, and NCF4. Patients with CD who carried mutations in these genes were
      3-fold more likely to have perianal disease (P = .0008) and stricturing
      complications (P = .002) than children with CD without these mutations. Among
      patients with CD with none of these mutations, 9% had undergone abdominal
      surgery; among patients with mutations in these NADPH oxidase genes, 31% had
      undergone abdominal surgery (P = .0004). A higher proportion of neutrophils from
      children with CD had low ROS production (47%) than from controls (15%) among the
      129 patients tested for ROS (P = .002). Minor alleles of the NADPH genes were
      detected in 7% of children with CD whose neutrophils produced normal levels of
      ROS vs 38% of children whose neutrophils produced low levels of ROS (P = .009).
      Neutrophils that produced low levels of ROS had specific alterations in genes
      that regulate glucose metabolism and antimicrobial responses. CONCLUSIONS: We
      identified missense mutations in genes that encode NADPH oxidases in children
      with CD; these were associated with a more aggressive disease course and reduced
      ROS production by neutrophils from the patients.

PMID- 29454794
TI  - HCV Genotype 6a Escape From and Resistance to Velpatasvir, Pibrentasvir, and
      Sofosbuvir in Robust Infectious Cell Culture Models.
AB  - BACKGROUND & AIMS: Chronic liver diseases caused by hepatitis C virus (HCV)
      genotype 6 are prevalent in Asia, and millions of people require treatment with
      direct-acting antiviral regimens, such as NS5A inhibitor velpatasvir combined
      with the NS5B polymerase inhibitor sofosbuvir. We developed infectious cell
      culture models of HCV genotype 6a infection to study the effects of these
      inhibitors and the development of resistance. METHODS: The consensus sequences of
      strains HK2 (MG717925) and HK6a (MG717928), originating from serum of patients
      with chronic HCV infection, were determined by Sanger sequencing of genomes
      amplified by reverse-transcription polymerase chain reaction. In vitro
      noninfectious full-length clones of these 6a strains were subsequently adapted in
      Huh7.5 cells, primarily by using substitutions identified in JFH1-based Core-NS5A
      and Core-NS5B genotype 6a recombinants. We studied the efficacy of NS5A and NS5B
      inhibitors in concentration-response assays. We examined the effects of long-term
      culture of Huh7.5 cells incubated with velpatasvir and sofosbuvir singly or
      combined following infection with passaged full-length HK2 or HK6a recombinant
      viruses. Resistance-associated substitutions (RAS) were identified by Sanger and
      next-generation sequencing, and their effects on viral fitness and in drug
      susceptibility were determined in reverse-genetic experiments. RESULTS: Adapted
      full-length HCV genotype 6a recombinants HK2cc and HK6acc had fast propagation
      kinetics and high infectivity titers. Compared with an HCV genotype 1a
      recombinant, HCV genotype 6a recombinants of strains HK2 and HK6a were equally
      sensitive to daclatasvir, elbasvir, velpatasvir, pibrentasvir, and sofosbuvir,
      but less sensitive to ledipasvir, ombitasvir, and dasabuvir. Long-term exposure
      of HCV genotype 6a-infected Huh7.5 cells with a combination of velpatasvir and
      sofosbuvir resulted in clearance of the virus, but the virus escaped the effects
      of single inhibitors via emergence of the RAS L31V in NS5A (conferring resistance
      to velpatasvir) and S282T in NS5B (conferring resistance to sofosbuvir).
      Engineered recombinant genotype 6a viruses with single RAS mediated resistance to
      velpatasvir or sofosbuvir. HCV genotype 6a viruses with RAS NS5A-L31V or NS5B
      S282T were however, able to propagate and escape in Huh7.5 cells exposed to the
      combination of velpatasvir and sofosbuvir. Further, HCV genotype 6a with NS5A
      L31V was able to propagate and escape in the presence of pibrentasvir with
      emergence of NS5A-L28S, conferring a high level of resistance to this inhibitor.
      CONCLUSIONS: Strains of HCV genotype 6a isolated from patients can be adapted to
      propagate in cultured cells, permitting studies of the complete life cycle for
      this important genotype. The combination of velpatasvir and sofosbuvir is
      required to block propagation of original HCV genotype 6a, which quickly becomes
      resistant to single inhibitors via the rapid emergence and persistence of RAS.
      These features of HCV genotype 6a could compromise treatment.

PMID- 29454795
TI  - Advances in CRC Prevention: Screening and Surveillance.
AB  - Colorectal cancer (CRC) is among the most commonly diagnosed cancers and causes
      of death from cancer across the world. CRC can, however, be detected in
      asymptomatic patients at a curable stage, and several studies have shown lower
      mortality among patients who undergo screening compared with those who do not.
      Using colonoscopy in CRC screening also results in the detection of precancerous
      polyps that can be directly removed during the procedure, thereby reducing the
      incidence of cancer. In the past decade, convincing evidence has appeared that
      the effectiveness of colonoscopy as CRC prevention tool is associated with the
      quality of the procedure. This review aims to provide an up-to-date overview of
      recent efforts to improve colonoscopy effectiveness by enhancing detection and
      improving the completeness and safety of resection of colorectal lesions.

PMID- 29454793
TI  - P300 Acetyltransferase Mediates Stiffness-Induced Activation of Hepatic Stellate
      Cells Into Tumor-Promoting Myofibroblasts.
AB  - BACKGROUND & AIMS: Hepatic stellate cells (HSCs) contribute to desmoplasia and
      stiffness of liver metastases by differentiating into matrix-producing
      myofibroblasts. We investigated whether stiffness due to the presence of tumors
      increases activation of HSCs into myofibroblasts and their tumor-promoting
      effects, as well as the role of E1A binding protein p300, a histone
      acetyltransferase that regulates transcription, in these processes. METHODS: HSCs
      were isolated from liver tissues of patients, mice in which the p300 gene was
      flanked by 2 loxP sites (p300F/F mice), and p300+/+ mice (controls). The HSCs
      were placed on polyacrylamide gels with precisely defined stiffness, and their
      activation (differentiation into myofibroblasts) was assessed by
      immunofluorescence and immunoblot analyses for alpha-smooth muscle actin. In HSCs
      from mice, the p300 gene was disrupted by cre recombinase. In human HSCs, levels
      of p300 were knocked down with small hairpin RNAs or a mutant form of p300 that
      is not phosphorylated by AKT (p300S1834A) was overexpressed. Human HSCs were also
      cultured with inhibitors of p300 (C646), PI3K signaling to AKT (LY294002), or
      RHOA (C3 transferase) and effects on stiffness-induced activation were measured.
      RNA sequencing and chromatin immunoprecipitation-quantitative polymerase chain
      reaction were used to identify HSC genes that changed expression levels in
      response to stiffness. We measured effects of HSC-conditioned media on
      proliferation of HT29 colon cancer cells and growth of tumors following
      subcutaneous injection of these cells into mice. MC38 colon cancer cells were
      injected into portal veins of p300F/Fcre and control mice, and liver metastases
      were measured. p300F/Fcre and control mice were given intraperitoneal injections
      of CCl4 to induce liver fibrosis. Liver tissues were collected and analyzed by
      immunofluorescence, immunoblot, and histology. RESULTS: Substrate stiffness was
      sufficient to activate HSCs, leading to nuclear accumulation of p300. Disrupting
      p300 level or activity blocked stiffness-induced activation of HSCs. In HSCs,
      substrate stiffness activated AKT signaling via RHOA to induce phosphorylation of
      p300 at serine 1834; this caused p300 to translocate to the nucleus, where it up
      regulated transcription of genes that increase activation of HSCs and metastasis,
      including CXCL12. MC38 cells, injected into portal veins, formed fewer metastases
      in livers of p300F/Fcre mice than control mice. Expression of p300 was increased
      in livers of mice following injection of CCl4; HSC activation and collagen
      deposition were reduced in livers of p300F/Fcre mice compared with control mice.
      CONCLUSIONS: In studies of mice, we found liver stiffness to activate HSC
      differentiation into myofibroblasts, which required nuclear accumulation of p300.
      p300 increases HSC expression of genes that promote metastasis.

PMID- 29454796
TI  - Endoscopic Myotomy for Foregut Motility Disorders.
AB  - Peroral endoscopic myotomy (POEM) is an advanced endoscopic procedure classically
      performed for the treatment of achalasia. The procedure is based on principles of
      submucosal endoscopy and is composed of a mucosal incision, submucosal tunneling,
      myotomy, and mucosal closure. Multiple published studies that collectively
      include more than 6000 patients reported clinical success in more than 80% to 90%
      of patients. Recent literature also suggested durability of response over a
      medium-term follow-up. POEM is associated with a low rate of adverse events when
      performed by experienced operators. Gastroesophageal reflux is not infrequent
      after POEM but does not seem significantly different from reflux that occurs
      after Heller myotomy. POEM also seems to be effective in the treatment of spastic
      esophageal disorders (eg, jackhammer and diffuse esophageal spasm). Last, the
      role of gastric POEM (G-POEM) in the treatment of gastroparesis has been
      investigated in recent studies with promising results.

PMID- 29454798
TI  - Functional Bowel Disorders.

PMID- 29454799
TI  - Identification of genomic variants causing sperm abnormalities and reduced male
      fertility.
AB  - Whole genome sequencing has identified millions of bovine genetic variants;
      however, there is currently little understanding about which variants affect male
      fertility. It is imperative that we begin to link detrimental genetic variants to
      sperm phenotypes via the analysis of semen samples and measurement of fertility
      for bulls with alternate genotypes. Artificial insemination (AI) bulls provide a
      useful model system because of extensive fertility records, measured as sire
      conception rates (SCR). Genetic variants with moderate to large effects on
      fertility can be identified by sequencing the genomes of fertile and subfertile
      or infertile sires identified with high or low SCR as adult AI bulls or yearling
      bulls that failed Breeding Soundness Evaluation. Variants enriched in frequency
      in the sequences of subfertile/infertile bulls, particularly those likely to
      result in the loss of protein function or predicted to be severely deleterious to
      genes involved in sperm protein structure and function, semen quality or sperm
      morphology can be designed onto genotyping assays for validation of their effects
      on fertility. High throughput conventional and image-based flow cytometry,
      proteomics and cell imaging can be used to establish the functional effects of
      variants on sperm phenotypes. Integrating the genetic, fertility and sperm
      phenotype data will accelerate biomarker discovery and validation, improve
      routine semen testing in bull studs and identify new targets for cost-efficient
      AI dose optimization approaches such as semen nanopurification. This will
      maximize semen output from genetically superior sires and will increase the
      fertility of cattle. Better understanding of the relationships between male
      genotype and sperm phenotype may also yield new diagnostic tools and treatments
      for human male and idiopathic infertility.

PMID- 29454797
TI  - Alterations in Intestinal Microbiota Lead to Production of Interleukin 17 by
      Intrahepatic gammadelta T-Cell Receptor-Positive Cells and Pathogenesis of
      Cholestatic Liver Disease.
AB  - BACKGROUND & AIMS: Variants at the ABCB4 or MDR2 locus, which encodes a biliary
      transport protein, are associated with a spectrum of cholestatic liver diseases.
      Exacerbation of liver disease has been linked to increased hepatic levels of
      interleukin (IL) 17, yet the mechanisms of this increase are not understood. We
      studied mice with disruption of Mdr2 to determine how defects in liver and
      alteration in the microbiota contribute to production of IL17 by intrahepatic
      gammadelta T cells. METHODS: We performed studies with Mdr2-/- and littermate
      FVB/NJ (control) mice. IL17 was measured in serum samples by an enzyme-linked
      immunosorbent assay. Mice were injected with neutralizing antibodies against the
      gammadelta T-cell receptor (TCR; anti-gammadelta TCR) or mouse IL17A (anti
      IL17A). Livers were collected and bacteria were identified in homogenates by
      culture procedures; TCRgammadelta+ cells were isolated by flow cytometry. Fecal
      samples were collected from mice and analyzed by 16S ribosomal DNA sequencing.
      Cells were stimulated with antibodies or bacteria, and cytokine production was
      measured. We obtained tissues from 10 patients undergoing liver transplantation
      for primary sclerosing cholangitis or chronic hepatitis C virus infection.
      Tissues were analyzed for cytokine production by gammadelta TCR+ cells. RESULTS:
      Mdr2-/- mice had collagen deposition around hepatic bile ducts and periportal
      bridging fibrosis with influx of inflammatory cells and increased serum levels of
      IL17 compared with control mice. Administration of anti-IL17A reduced hepatic
      fibrosis. Livers from Mdr2-/- mice had increased numbers of IL17A+ gammadeltaTCR+
      cells-particularly of IL17A+ Vgamma6Jgamma1 gammadelta TCR+ cells. Fecal samples
      from Mdr2-/- mice were enriched in Lactobacillus, and liver tissues were enriched
      in Lactobacillus gasseri compared with control mice. Mdr2-/- mice also had
      increased intestinal permeability. The gammadelta TCR+ cells isolated from Mdr2-/
      livers produced IL17 in response to heat-killed L gasseri. Intraperitoneal
      injection of control mice with L gasseri led to increased serum levels of IL17
      and liver infiltration by inflammatory cells; injection of these mice with anti
      gammadelta TCR reduced serum level of IL17. Intravenous injections of Mdr2-/-
      mice with anti-gammadelta TCR reduced fibrosis; liver levels of IL17, and
      inflammatory cells; and serum levels of IL17. gammadeltaTCR+ cells isolated from
      livers of patients with primary sclerosing cholangitis, but not hepatitis C virus
      infection, produced IL17. CONCLUSIONS: In Mdr2-/- mice, we found development of
      liver fibrosis and inflammation to require hepatic activation of gammadelta TCR+
      cells and production of IL17 mediated by exposure to L gasseri. This pathway
      appears to contribute to development of cholestatic liver disease in patients.

PMID- 29454800
TI  - Remarkable improved electro-Fenton efficiency by electric-field-induced catalysis
      of CeO2.
AB  - In this study, we designed a novel combined electro-Fenton system for the
      treatment of wastewater containing biological recalcitrant using electric-field
      induced ceria (CeO2) as the synergistic catalysts. It was found that by applying
      this CeO2 electro-Fenton system, the current efficiency improved from 74.49% to
      109.82% within 2.5 min; the removal efficiency for dimethyl phthalate (DMP)
      increased from 85.5% to 94.9% within 20 min; and the mineralization rate
      increased from 76.01% to 93.58% after 120 min. The effects of parameters such as
      the applied potential, electrolyte, and concentration of Fe2+ on the current
      efficiency were systematically studied. Investigations by LSV, zeta titration, X
      ray photoelectron spectroscopy (XPS), X-Ray Diffraction (XRD)and electron spin
      resonance (ESR)revealed the reasons for achieving a current efficiency of over
      100% in the CeO2 electro-Fenton system. A mechanism that involved Bronsted acid
      sites and the redox cycle of sulfate CeO2 was proposed.

PMID- 29454801
TI  - The influence of Pb addition on the properties of fly ash-based geopolymers.
AB  - Preventing or reducing negative effects on the environment from the waste
      landfilling is the main goal defined by the European Landfill Directive.
      Generally geopolymers can be considered as sustainable binders for immobilization
      of hazardous wastes containing different toxic elements. In this paper the
      influence of addition of high amount of lead on structure, strength, and leaching
      behavior (the effectiveness of Pb immobilization) of fly ash-based geopolymers
      depending on the geopolymer curing conditions was investigated. Lead was added
      during the synthesis of geopolymers in the form of highly soluble salt - lead
      nitrate. Structural changes of geopolymers as a result of lead
      addition/immobilization were assessed by means of XRD, SEM/EDS, and 29Si MAS NMR
      analysis. Investigated curing conditions significantly influenced structure,
      strength and leaching behavior of geopolymers. High addition of lead caused a
      sizeable decrease in compressive strength of geopolymers and promoted formation
      of aluminum-deficient aluminosilicate gel (depolymerization of aluminosilicate
      gel), regardless of the curing conditions investigated. According to the EUWAC
      limitations, 4% of lead was successfully immobilized by fly ash-based geopolymers
      cured for 28 days in a humid chamber at room temperature.

PMID- 29454802
TI  - Vangl2 is essential for myocardial remodeling activated by Wnt/JNK signaling.
AB  - The Wnt/JNK pathway, responsible for tissue polarity in cardiogenesis in
      vertebrates, has been shown to play numerous roles during differentiation and
      development of cardiac myocytes. Van Gogh-like-2 (Vangl2) is a core component
      that regulates the induction of polarized cellular and tissue morphology during
      animal development. However, little is known about Wnt/JNK signaling pathway in
      the process of myocardial remodeling. In present study, we found that activation
      of Wnt/JNK signaling by Wnt5a stimulates enlargement of cardiomyocyte surface
      area. The hypertrophic features were inhibited in Vangl2 depleted cells.
      Meanwhile, Wnt/JNK activation induced cytoskeleton rearrangement but failed to
      activate these effects in cells lacking Vangl2. Moreover, Wnt/JNK activation
      significantly increased the cell apoptosis by mediating the mitochondrial
      permeability transition pore (mPTP) dysfunction, whereas knockdown of Vangl2
      partly reversed these effects. These results suggest that activation of Wnt/JNK
      signaling stimulates myocardial remodeling (cell morphological changes, apoptosis
      and mitochondrial dysfunction), in which Vangl2 may play an essential role.

PMID- 29454803
TI  - Physics of mind: A new perspective to understand better the external world by
      looking inside our brain: Comment on "Physics of mind: Experimental confirmations
      of theoretical predictions" by Felix Schoeller et al.

PMID- 29454804
TI  - Physiological predictors of leptin vary during menses and ovulation in healthy
      women.
AB  - Although research has shown interactions between the reproductive system and
      energy homeostasis, it is not clear how environmental or behavioral factors may
      factor into these associations. Here we aimed to determine how changes in
      reproductive state (i.e., phase of the menstrual cycle) and other behavioral and
      physiological factors may influence leptin levels in healthy women, as well as
      how sexual activity may play a role in leptin modulation. We collected serum and
      saliva from 32 healthy women and measured leptin, estradiol, and progesterone.
      Participants also completed surveys of demographics, health and sexual behaviors,
      and physical activity. Leptin was predicted by meals per day and missed meals at
      both menses and ovulation. However, estradiol and physical activity were stronger
      predictors of leptin at menses, while sexual activity was a stronger predictor of
      leptin at ovulation. These findings suggest that predictors of serum leptin, and
      possibly energy storage and expenditure, vary across the menstrual cycle.

PMID- 29454806
TI  - Oxidative imbalance in mice intoxicated by microcystin-LR can be minimized.
AB  - Microcystins-LR (MC-LR) is a cyanotoxin produced by cyanobacteria. We evaluated
      the antioxidant potential of LASSBio-596 (LB-596, inhibitor of phosphodiesterases
      4 and 5), per os, and biochemical markers involved in lung and liver injury
      induced by exposure to sublethal dose of MC-LR. Fifty male Swiss mice received an
      intraperitoneal injection of 60 MUL of saline (CTRL group, n = 20) or a sublethal
      dose of MC-LR (40 MUg/kg, TOX group, n = 20). After 6 h the animals received
      either saline (TOX and CTRL groups) or LB-596 (50 mg/kg, TOX + LASS group, n =
      10) by gavage. At 6 h after exposure, respiratory mechanics was evaluated in 10
      CTRL and 10 TOX mice: there was a significant increase of all lung mechanics
      parameters (static elastance, viscoelastic component of elastance and lung
      resistive and viscoelastic/inhomogeneous pressures) in TOX compared to CTRL. 8 h
      after saline or MC-LR administration, i.e., 2 h after treatment with LB-596,
      blood serum levels of alanine aminotransferase and aspartate aminotransferase,
      activity of superoxide dismutase, catalase, and content of malondialdehyde and
      carbonyl in lung and liver, NADPH oxidase 2 and 4 mRNA expressions, dual oxidase
      enzyme activity and H2O2 generation were analyzed in lung homogenates. All
      parameters were significantly higher in TOX than in the other groups. There was
      no significant difference between CTRL and TOX + LASS. MC-LR deteriorated lung
      and liver functions and induced redox imbalance in them, which was prevented by
      oral administration of LB-596.

PMID- 29454805
TI  - Mouse preantral follicle growth in 3D co-culture system using human menstrual
      blood mesenchymal stem cell.
AB  - Follicle culture provides a condition which can help investigators to evaluate
      various aspects of ovarian follicle growth and development and impact of
      different components and supplementations as well as presumably application of
      follicle culture approach in fertility preservation procedures. Mesenchymal Stem
      Cells (MSCs), particularly those isolated from menstrual blood has the potential
      to be used as a tool for improvement of fertility. In the current study, a 3D co
      culture system with mice preantral follicles and human Menstrual Blood
      Mesenchymal Stem Cells (MenSCs) using either collagen or alginate beads was
      designed to investigate whether this system allows better preantral follicles
      growth and development. Results showed that MenSCs increase the indices of
      follicular growth including survival rate, diameter, and antrum formation as well
      as the rate of in vitro maturation (IVM) in both collagen and alginates beads.
      Although statistically not significant, alginate was found to be superior in
      terms of supporting survival rate and antrum formation. Hormone assay
      demonstrated that the amount of secreted 17 beta-estradiol and progesterone in
      both 3D systems increased dramatically after 12 days, with the highest levels in
      system employing MenSCs. Data also demonstrated that relative expression of
      studied genes increased for Bmp15 and Gdf9 and decreased for Mater when follicles
      were cultured in the presence of MenSCs. Collectively, results of the present
      study showed that MenSCs could improve indices of follicular growth and
      maturation in vitro. Further studies are needed before a clinical application of
      MenSCs-induced IVM is considered.

PMID- 29454807
TI  - Characterization of chronic obstructive pulmonary disease prescribing patterns in
      the United States.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third-leading
      cause of death in the United States. Guideline recommendations for medication
      therapy include the use of inhaled medications for management of stable COPD.
      There are limited data available describing prescribing percentages of
      medications in patients with COPD. AIM: To determine the prescribing percentages
      of medications for COPD in a national, cross-sectional study. METHODS: This was a
      national, cross-sectional study using data from the National Ambulatory Medical
      Care Survey (NAMCS) in 2013. Patients were included if they had an International
      Classification of Diseases (ICD) 9 code for COPD and were greater than 18 years
      of age. Data describing patient demographics, provider demographics and
      prescribed medications were collected. Data were analyzed using sample weights to
      account for the multi-stage sample design. RESULTS: On weighted analysis,
      15,821,000 patient visits were included. Patients were predominantly female,
      greater than 40 years of age and white, non-Hispanic. The most common provider
      type was primary care provider. At least one COPD medication was prescribed to
      64.8% of included patients. Prescription of short-acting bronchodilators was most
      common in this cohort and observed at a percentage of 42.5%. A long-acting
      bronchodilator or inhaled corticosteroid was prescribed to 32.3% of included
      patients. The most common long-acting bronchodilator used was long-acting beta
      agonist therapy in 21.3% of patients. CONCLUSION: This study describes patients
      with COPD from a nationally representative sample. The percentage of maintenance
      medication prescribing indicates further opportunity for medication optimization
      in the outpatient setting for patients with COPD.

PMID- 29454808
TI  - A new multifunctionalized material against multi-drug resistant bacteria and
      abnormal osteoclast activity.
AB  - The development of new biomaterials able to favor bone formation and to inhibit
      bone abnormal resorption is mandatory to face the increasing number of age
      related musculo-skeletal disorders. Moreover, the increasing antibiotic
      resistance of clinically important bacteria, which is among the main causes of
      implant failure, requires new antimicrobial systems. In this study, we prepared
      multifunctional materials consisting of hydroxyapatite-zoledronate composite
      crystals decorated with Ag Nanoparticles (AgNPs). Zoledronate, a potent
      bisphosphonate widely applied for the treatment of pathologies associated to
      abnormal bone loss, was incorporated into hydroxyapatite up to about 8 wt%.
      Loading of poly(ethylenimine) - stabilized AgNPs onto the crystals was promoted
      by zoledronate functionalization and provoked a significant variation of the
      values of zeta potential. The results of in vitro tests demonstrate that the
      multifunctional materials combine the beneficial actions of zoledronate and
      AgNPs. In fact, they improve osteoblast differentiation and activity, whereas
      they inhibit osteoclastogenesis and osteoclast differentiation, and significantly
      hinder the growth of multi-drug resistant Gram positive and Gram negative
      bacteria. As a consequence, they can be exploited both as antiresorptive agents
      and as antimicrobial materials able to prevent the development of bone-associated
      infections.

PMID- 29454809
TI  - The hidden lipoproteome of Staphylococcus aureus.
AB  - Lipoproteins are attached to the outer leaflet of the membrane by a di- or tri
      acylglyceryl moiety and are thus positioned in the membrane-cell wall interface.
      Consequently, lipoproteins are involved in many surface associated functions,
      including cell wall synthesis, electron transport, uptake of nutrients, surface
      stress response, signal transduction, and they represent a reservoir of bacterial
      virulence factors. Inspection of 123 annotated Staphylococcus aureus genome
      sequences in the public domain revealed that this organism devotes about 2-3% of
      its coding capacity to lipoproteins, corresponding to about 70 lipoproteins per
      genome. 60 of these lipoproteins were identified in 95% of the genomes analyzed,
      which thus constitute the core lipoproteome of S. aureus. 30% of the conserved
      staphylococcal lipoproteins are substrate-binding proteins of ABC transporters
      with roles in nutrient transport. With a few exceptions, much less is known about
      the function of the remaining lipoproteins, representing a large gap in our
      knowledge of this functionally important group of proteins. Here, we summarize
      current knowledge, and integrate information from genetic context analysis,
      expression and regulatory data, domain architecture, sequence and structural
      information, and phylogenetic distribution to provide potential starting points
      for experimental evaluation of the biological function of the poorly or
      uncharacterized lipoproteome of S. aureus.

PMID- 29454810
TI  - Predictors of functional outcome after hanging injury.
AB  - PURPOSE: Suicide becomes a serious problem in today's society and hanging is a
      common method of suicide. We want to find the factors which can predict the final
      functional outcomes of these cases. METHODS: All patients who presented to
      Accident and Emergency Department (ED) of the National Cheng Kung University
      Hospital from 1st January 2005 to 31th December 2013 with a hanging injury were
      included in this study. All cases were divided into good outcome group and bad
      outcome group according to Glasgow Outcome Scale (GOS). Data was analyzed by Mann
      Whitney test and chi-square test. RESULTS: Glasgow Coma Scale (GCS) < 3, pupil
      dilation and no pupillary light reflex both at the scene and ED were the factors
      to indicate poor functional outcome. Out-hospital cardiac arrest (OHCA), acidosis
      (pH < 7.2) and the need for intubation once arriving at ED were also related to
      poor functional outcome. OHCA cases all had poor functional outcome. CONCLUSION:
      GCS, pupil size, pupillary light reflex, OHCA and acidosis are useful as
      prognostic factors. GCS = 3 lead to a very poor outcome. However, the functional
      outcome seems good in patients with GCS>3. There parameters can help to predict
      the outcome before treatment.

PMID- 29454811
TI  - Examining parental monitoring as a moderator of the relationship between
      depressed mood and alcohol use and problems.
AB  - BACKGROUND: The comorbidity of depressed mood and college student drinking causes
      consequences for both the individual and society. Aspects of parenting have been
      shown to be important for college students' well-being. While some interventions
      are beginning to address this population, few studies have examined how parental
      monitoring impacts the relationship between depressed mood, alcohol use, and
      related consequences. The present study examined whether perceived parental
      monitoring moderated the relationship between depressed mood and alcohol use and
      related problems. METHODS: Students (N = 796) completed a survey during the fall
      semester of their first two years of college at a large, public university
      assessing drinking and related negative consequences, maternal and paternal
      monitoring, and depressed mood. RESULTS: Results revealed that maternal and
      paternal monitoring moderated the relationship between depressed mood and typical
      weekly drinking, and depressed mood and consequences (i.e., self-perception, self
      care, blackouts). CONCLUSIONS: Interventions should be tailored to parents based
      on considerations of both student mental health and alcohol use.

PMID- 29454812
TI  - Impulsivity-related traits, college alcohol beliefs, and alcohol outcomes:
      Examination of a prospective multiple mediation model among college students in
      Spain, Argentina, and USA.
AB  - OBJECTIVES: The present study examined (both cross-sectionally and prospectively)
      the mediational role of college alcohol beliefs in the relationship between
      impulsivity-related traits and alcohol outcomes (i.e., alcohol use and negative
      consequences) among college student drinkers from the United States (U.S.),
      Spain, and Argentina. METHOD: A sample of 1429 (U.S. = 733, Spain = 292,
      Argentina = 404) drinkers (at least one drinking episode within the previous
      month) completed the baseline survey, and 242 drinkers completed the follow-up.
      To test study aims, a cross-sectional model was first employed to examine whether
      the proposed double-mediated paths (i.e., each dimension of impulsivity ->
      college alcohol beliefs -> alcohol use -> negative alcohol-related consequences)
      extends across samples with different cultural backgrounds (i.e., structural
      invariance testing). A longitudinal model was then conducted to assess if college
      alcohol beliefs prospectively mediate the associations between trait impulsivity
      and alcohol outcomes. RESULTS: College alcohol beliefs were concurrently and
      prospectively associated with both greater alcohol use and increased number of
      negative alcohol-related consequences. These internalized beliefs about college
      student drinking culture significantly mediated the effects of several distinct
      impulsivity-related traits on alcohol-related outcomes including urgency
      (positive and negative), sensation seeking, and perseverance. These findings were
      invariant across gender and across three countries (Argentina, Spain, and the
      U.S.). CONCLUSIONS: Our findings highlight the modulatory role of cognitive
      factors on problematic alcohol use among college students with different cultural
      backgrounds. Our results suggest that, despite the cultural differences exhibited
      by these three countries, the unique and mediational effects of college alcohol
      beliefs appear relatively universal.

PMID- 29454813
TI  - Development and psychometric evaluation of a new measure to assess pregaming
      motives in Spanish-speaking young adults.
AB  - AIMS: The present study was divided into two different stages that sought to
      develop (Stage 1) and validate (Stage 2) the Argentinean-version of the Pregaming
      Motives Questionnaire (PMQ-Arg), a new, ecologically valid measure to assess
      pregaming (i.e., the consumption of alcohol prior to attending a social/sporting
      event where alcohol may or may not be available) motives among Spanish-speaking
      youth. METHOD: Two separate samples of Argentinian young adults (all last-year
      pregamers) were recruited by disseminating an invitation through online social
      networks and e-mail listings. RESULTS: In Stage 1, a total of 635 participants
      answered an open-ended question about their reasons for pregaming. In Stage 2
      (n=361), exploratory factor analysis was conducted with the preliminary set of
      high-quality, high-frequency pregaming motives that were obtained in Stage 1,
      yielding a final 23-item measure that was grouped in four factors: (i)
      Intoxication and Fun, (ii) Gathering and Social Enhancement, (iii) Going with the
      Flow, and (iv) Beverage Preference. Despite some broad similarities with measures
      that were developed with U.S. young adults, the present results indicated that
      the narrow content of some items of the PMQ-Arg were somewhat unique, possibly
      reflecting cultural differences between the United States and Argentina. The
      findings supported the adequate reliability, discriminant validity, convergent
      validity, and criterion-related validity of PMQ-Arg scores. CONCLUSIONS: The
      findings suggest that the PMQ-Arg meets the psychometric requirements of validity
      and reliability for its use to assess reasons for pregaming among Spanish
      speaking youth.

PMID- 29454814
TI  - Smoking behaviour and sensations during the pre-quit period of an exercise-aided
      smoking cessation intervention.
AB  - INTRODUCTION: Previous research has shown reductions in cigarette consumption
      during the pre-quit period of exercise-aided smoking cessation interventions.
      Smoking topography and sensation patterns during this period is unknown and may
      provide valuable insight into compensation and cessation readiness. METHODS:
      Female smokers (N = 236, M age = 43, M cigarettes/day = 17.0) enrolled in an
      exercise-aided smoking cessation intervention self-reported daily cigarette use
      and cigarette sensory experiences. Breath carbon monoxide and smoking topography
      data were collected during the period leading up to the targeted quit date (i.e.,
      baseline, week 1, and week 3), which was set for week 4. RESULTS: Repeated
      measures ANOVAs revealed that cigarette consumption (p < 0.001, eta = 0.32),
      carbon monoxide (p < 0.001, eta = 0.14), puff duration (p = 0.01, eta = 0.05),
      smoking satisfaction (p < 0.001, eta = 0.34), psychological reward (p < 0.001,
      eta = 0.43), enjoyment of respiratory tract sensations (p < 0.001, eta = 0.29),
      and craving (p < 0.001, eta = 0.39) decreased, whereas average puff flow (p =
      0.01, eta = 0.05) increased. CONCLUSIONS: This is the first study to establish
      that regular exercise during the pre-quit period served as a conduit for
      facilitating behavioral and sensory harm reduction with cigarettes. Furthermore,
      the pattern of change observed between cigarette consumption and smoking
      topography does not support compensation. These findings imply that female
      smokers who exercise prior to a quit attempt are in a favourable state to achieve
      cessation.

PMID- 29454815
TI  - Modelling the driving forces of the municipal solid waste generation in touristic
      islands. A case study of the Balearic Islands (2000-2030).
AB  - The improvement of municipal solid waste (MSW) management in touristic islands
      has not been sufficiently studied, and by using the Spanish Balearics as a case
      study, a hybrid methodology has been developed which: (i) identifies the three
      most influential variables (driving forces) of the MSW generation system through
      an econometric model based on official historical data for a given period (2000
      2014), (ii) develops a System Dynamics (SD) model of the evolution of MSW
      generation in this archipelago based on the same data and time period, and (iii)
      forecasts the performance of the MSW management system for a future period (2015
      2030). Six different scenarios are considered with varying assumptions,
      objectives and management policies, while applying Scenario Analysis to the SD
      model developed. The results show that by maintaining the current policies
      ("business as usual" BAU scenario) it will be impossible to meet the goals set by
      the Regional and the Spanish National Plans based on the European MSW Directive.
      However, by implementing the improvements proposed in the simulated alternative
      scenarios, the model predicts that by 2030, generation of MSW will have increased
      by 15% compared to 2014, mainly due to the effect of the Tourist Population which
      is 37.5% higher than the Resident Population. In addition, for the most
      optimistic scenario, the amount of MSW sent to landfills would decrease by 40%,
      and selective collection would increase by 30%, compared to 2014.

PMID- 29454816
TI  - Optimization of granular waste production based on mechanical properties.
AB  - Pellet production of food and agricultural wastes is a suitable method to supply
      livestock feed. Mechanical properties of pellets play an important role in their
      handling and transportation. In this study, the mechanical properties of pellets
      made from waste are investigated. After the pelleting process, the pellets were
      dried with a laboratory convective hot air dryer until reaching a safe moisture
      content. The effects of feedstock moisture content (0.54, 0.88, and 1.2 kgw kgDM
      1), particle size (PS < 0.4, 0.4 < PS<1.2, and 1.2 < PS<2 mm), drying temperature
      (318, 333, and 348 K) and infrared radiation power of the dryer (0, 500, and 1000
      W) on pellet durability, impact resistance, and compressive strength were
      investigated for two diets. The results showed that the mechanical properties of
      the pellets increased with decreasing particle size of the raw materials. The
      feedstock moisture content also affected the durability, impact resistant, and
      compressive strength of pellets. Moreover, mechanical properties were reduced
      considerably when the pellets were dried at a high temperature and infrared
      power. The diet with a lower fat content as well as a lower neutral detergent
      fiber indicated a higher pellet quality. Furthermore, the combination of raw
      materials and optimization of pelleting and drying conditions had a significant
      effect on the quality of the produced pellets.

PMID- 29454817
TI  - Investigating the feasibility of a reuse scenario for textile fibres recovered
      from end-of-life tyres.
AB  - The management of end-of-life tyres (ELTs) is regulated by several national and
      international legislations aiming to promote the recovery of materials and energy
      from this waste. The three main materials used in tyres are considered: rubber
      (main product), which is currently reused in other closed-loop applications;
      steel, which is used for the production of virgin materials; and textile fibres
      (approximately 10% by weight of ELTs), which are mainly incinerated for energy
      recovery (open-loop scenario). This study aims to propose and validate a new
      closed-loop scenario for textile fibres based on material reuse for bituminous
      conglomerates. The final objective is to verify the technical, environmental,
      financial, and economic feasibility of the proposed treatment process and reuse
      scenario. After characterization of the textile material, which is required to
      determine the technological feasibility, a specific process has been developed to
      clean, compact, and prepare the fibres for subsequent reuse. A life cycle
      assessment (LCA) has been carried out to quantify the environmental benefits of
      reusing the fibres. Finally, a cost benefit analysis based on the LCA results was
      conducted to establish the long-term financial and economic sustainability. From
      a technological point of view, the tyre textile fibres could be a promising
      substitute to the reinforcement cellulose commonly used in asphalts as long as
      the fibres are properly prepared (compaction and pellet production) for
      application in the standard bituminous conglomerate production process. From an
      environmental point of view, relevant benefits in terms of global warming
      potential and acidification potential reduction were observed in comparison with
      the standard incineration for energy recovery (respectively -86% and -45%).
      Moreover, the proposed scenario can be considered as financially viable in the
      medium to long term (cumulative generated cash flow is positive after the 5th
      year) and economically sustainable (expected net present value of more than
      ?3,000,000 and economic rate of return of approximately 30%). Finally, the
      sensitivity and risk analyses show that no specific issues are foreseen for the
      future implementation in real industrial applications.

PMID- 29454818
TI  - Comprehensive characterization of printed circuit boards of various end-of-life
      electrical and electronic equipment for beneficiation investigation.
AB  - Comprehensive characterization of printed circuit board (PCB) of end-of-life
      electrical and electronic equipment (EEE) is obligatory for prospective
      profitable beneficiation. In this study, beneficiation oriented comprehensive
      characterization of two brands of PCBs each of 16 end-of-life EEE was conducted
      in terms of their physicochemical characteristics with special emphasis on the
      content of 16 general elements, 2 precious metals and 15 rare earth elements
      (REEs). General elements and their highest weight percent composition found in
      different PCBs of the EEEs were Cu (23% in laptop), Al (6% in computer), Pb (15%
      in DVD player) and Ba (7% in TV). The high abundant of precious metals such as Au
      (316 g/ton) and Ag (636 g/ton) in mobile phone and laptop, respectively coupled
      with rapid obsolescence age makes waste PCBs of information technology and
      telecommunication equipment the most potent resource reservoir. Additionally,
      most of the waste PCBs were observed to contain REEs in considerable quantity
      with Sc up to 31 g/ton and Ce up to 13 g/ton being the major constituents.
      Comprehensive characterization of waste PCBs therefore will systematically help
      towards better understanding of e-waste recycling processes for beneficiation
      purpose and sustainable resource circulation and conservation.

PMID- 29454819
TI  - Some inferences still take time: Prosody, predictability, and the speed of scalar
      implicatures.
AB  - Experimental pragmatics has gained many insights from understanding how people
      use weak scalar terms (like some) to infer that a stronger alternative (like all)
      is false. Early studies found that comprehenders initially interpret some without
      an upper bound, but later results suggest that this inference is sometimes
      immediate (e.g., Grodner, Klein, Carbary, & Tanenhaus, 2010). The present paper
      explores whether rapid inferencing depends on the prosody (i.e., summa rather
      than some of) or predictability of referring expressions (e.g., consistently
      using some to describe subsets). Eye-tracking experiments examined looks to
      subsets (2-of-4 socks) and total sets (3-of-3 soccer balls) following some and
      found early preferences for subsets in predictable contexts but not in less
      predictable contexts (Experiment 1 and 2). In contrast, there was no reliable
      prosody effect on inferencing. Changes in predictability did not affect judgments
      of the naturalness of some, when a discourse context was available (Experiment
      3). However, predictable contexts reduced variability in speakers' descriptions
      of subsets and total sets (Experiment 4). Together, these results demonstrate
      that scalar inferences are often delayed during comprehension, but reference
      restriction is rapid when set descriptions can be formulated beforehand.

PMID- 29454820
TI  - IL12B, IL23A, IL23R and HLA-C*06 genetic variants in psoriasis susceptibility and
      response to treatment.
AB  - The role of interleukin-23 is crucial in the pathogenesis of psoriasis, and
      IL23A, IL12B and IL23R genetic variants have been associated with the disease in
      genome-wide association studies. In the current paper we have conducted a
      confirmation study of the abovementioned genetic factors in a case-control
      analysis of 507 psoriatic patients and 396 controls from a Polish population, and
      subsequently analyzed the impact of genetic variants on response to topical and
      NB-UVB therapy in a subset of 306 patients. Case-control analysis revealed an
      association of IL12B rs3212227 and IL23R rs11209026 minor allele carrier status
      with reduced odds for psoriasis (OR = 0.66, 95%CI: 0.50-0.87, and OR = 0.41,
      95%CI: 0.26-0.67, respectively), while HLA-C*06 allele carriers were more
      frequent in patients group (OR = 4.56, 95%CI: 3.41-6.10). The studied polymorphic
      variants of IL12B, IL23A, and IL23R genes did not influence therapy outcome, i.e.
      there were no significant differences in PASI reduction between patients with
      different genotypes. However, HLA-C*06 carriers showed poorer response to the
      applied treatment, when compared to non-carriers. The results of the current
      study confirm an association between IL12B and IL23R genetic polymorphism and
      psoriasis vulgaris (with a protective effect of minor alleles). HLA-C*06 carriers
      show reduced effectiveness of topical/NB-UVB therapy, and that observation could
      be potentially used in treatment personalization.

PMID- 29454822
TI  - Premature mortality in single fathers.

PMID- 29454821
TI  - Mortality in single fathers compared with single mothers and partnered parents: a
      population-based cohort study.
AB  - BACKGROUND: Single parent families, including families headed by single fathers,
      are becoming increasingly common around the world. Previous evidence suggests
      that single parenthood is associated with adverse health outcomes and increased
      mortality; however, most studies have focused on single mothers, with little
      known about the health of single fathers. This study aimed to examine mortality
      in a large population-based sample of Canadian single fathers compared with
      single mothers and partnered fathers and mothers. METHODS: We used a
      representative sample of 871 single fathers, 4590 single mothers, 16 341
      partnered fathers, and 18 688 partnered mothers from the Canadian Community
      Health Survey (cycles 2001-12; earliest survey date: Sept 5, 2000; latest survey
      date: Dec 24, 2012). We anonymously linked survey participants to health
      administrative database records to ascertain health status at baseline and
      mortality from survey date up to Oct 28, 2016. We included individuals who were
      aged 15 years or older, living in a household with one or more biological or
      adopted child younger than 25 years, and living in Ontario, and we excluded those
      who left Ontario during the study period or had data discrepancies. Single
      parents were defined as those who were divorced, separated, widowed, or single,
      never-married, and non-cohabitating, and partnered parents were defined as those
      who were married or common-law partners. We investigated differences in mortality
      using Cox proportional hazards models with adjustment for sociodemographic,
      lifestyle, and clinical factors. FINDINGS: Median follow-up was 11.10 years (IQR
      7.36-13.54). Mortality in single fathers (5.8 per 1000 person-years) was three
      times higher than rates in single mothers (1.74 per 1000 person-years) and
      partnered fathers (1.94 per 1000 person-years). Single fathers had a
      significantly higher adjusted risk of dying than both single mothers (hazard
      ratio [HR] 2.49, 95% CI 1.20-5.15; p=0.01) and partnered fathers (2.06, 1.11
      3.83; p=0.02). INTERPRETATION: In this first head-to-head comparison of mortality
      across single and partnered parent groups, we found that single fathers had the
      least favourable risk factor profile and greatest risk of mortality. Social
      histories might help physicians identify these high-risk patients. Further work
      is needed to understand the causes of this high mortality risk and how clinical
      and public health interventions can improve lifestyle and behavioural risk
      factors. FUNDING: Ontario Ministry of Health and Long-Term Care.

PMID- 29454823
TI  - Identification and isolation of infective filamentous particles in Infectious
      Salmon Anemia Virus (ISAV).
AB  - The infectious salmon anemia virus (ISAV) is an aquatic pathogen that is a member
      of the Orthomyxoviridae family with lethal hemorrhagic potential. Although it
      affects other species of salmonid fish, ISAV only causes disease in Atlantic
      salmon (Salmo salar) specimens in sea water. In spite of the fact that the virus
      has been described as enveloped with icosahedral symmetry, viral like particles
      with anomalous morphology have been observed in field samples, this we have not
      been able to recover then in adequate quantities for full demonstration. We
      report a procedure to concentrate and recover these novel forms of the virus,
      comparing two cell lines from different origins, demonstrating that these forms
      were preferentially expressed in cells of epithelial origin.

PMID- 29454825
TI  - Reply to "Adherence to oral cancer therapy in older adults: The International
      Society of Geriatric Oncology (SIOG) taskforce recommendations" by Mislang et al.

PMID- 29454824
TI  - Candida albicans - Biology, molecular characterization, pathogenicity, and
      advances in diagnosis and control - An update.
AB  - Candida albicans is an emerging multidrug-resistant fungal pathogen representing
      an important source of invasive disease in humans and generating high healthcare
      costs worldwide. This fungus is frequently found in different anatomical sites of
      healthy persons and could induce systemic and superficial infections under
      optimal environmental conditions. Invasive candidiasis (IC) is an important
      nosocomial infection with high morbidity and mortality rates in hospitalized
      children. It represents a major source of prolonged infections in intensive care
      unit (ICU), particularly in immunosuppressed or elderly patients. Clinical
      diagnosis of candidiasis could be difficult because of the lack of specific
      symptoms and clinical signs. Although C. albicans is the most frequently isolated
      Candida species in IC, non-albicans Candida (NAC) species are also commonly
      detected. Multilocus enzyme electrophoresis (MLEE), fragment length polymorphism
      (RFLP), electrophoretic karyotyping (EK), and random amplified polymorphic DNA
      (RAPD), multilocus sequence typing (MLST) are known as an efficient technique
      used for molecular typing of Candida species. The efficacy of antifungal
      treatment against candidiasis has been evaluated and discussed in the context of
      large epidemiological studies. The present review highlights the etiology,
      epidemiology, molecular typing, commensalism and virulence factors, along with
      the appropriate prevention and control strategies regarding this widespread
      pathogen.

PMID- 29454826
TI  - Diagnosis, follow-up and management of sleep-disordered breathing in children
      with osteogenesis imperfecta.
AB  - OBJECTIVES: Osteogenesis imperfecta (OI) is the most common genetic skeletal
      disorder. Extraskeletal findings are common but an association with sleep
      disordered breathing (SDB) has never been described. The aim of this study was to
      investigate clinical features of children with OI and suspected SDB. METHODS: A
      retrospective study of clinical records, signs of SDB and polysomnographic
      recordings of children with OI was performed. We paid particular attention to
      symptoms that could be associated with SDB in this population - scoliosis,
      kyphosis, vertebral arthrodesis, chest wall deformities, basilar impression,
      autonomy - as well as data already known to be associated with obstructive sleep
      apnea such as body mass index and upper-airway impairment. RESULTS: We reviewed
      the clinical charts of 188 patients referred to our genetic skeletal disorders
      reference center for OI. Among the 15 patients (8%) with polysomnographic
      recordings, 12 (6.4%) had sleep-disordered breathing. We found a negative
      correlation between the Brief Assessment of Motor Function score and Apnea
      Hypopnea Index (r=-0.68; p=0.01) and Desaturation Index (r=-0.62; p=0.02). The
      Apnea Hypopnea Index was higher for non-walkers than walkers (mean [SD]: 6.5
      [3.6] vs. 2.4 [1.5]; p=0.02) and with type III versus IV OI. Two patients were
      started on continuous positive airway pressure ventilation, with clinical
      improvement. CONCLUSION: For OI children, symptoms suggesting obstructive sleep
      disorders should be searched for systematically, especially in children with
      compromised autonomy, high body mass index, trunk deformations, and severe OI
      type.

PMID- 29454827
TI  - Development of thermostable amylase enzyme from Bacillus cereus for potential
      antibiofilm activity.
AB  - The marine bacterial strain Bacillus cereus was used to produce amylase enzyme
      and has excellent alkali-stable and thermostable enzymatic activity. The combined
      effects of pH, temperature and incubation time on amylase activity were studied
      using response surface methodology. The amylase enzyme activity was also
      determined in the presence of various metal ions, chelating agents, detergents
      and the results showed that the maximum enzyme activity was observed in the
      presence of calcium chloride (96.1%), EDTA (63.4%) and surf excel (90.6%). The
      amylase enzyme exhibited excellent antibiofilm activity against marine derived
      biofilm forming bacteria Pseudomonas aeruginosa and Staphylococcus aureus in
      microtiter plate assay and congo red assay. Light and confocal laser scanning
      microscopic (CLSM) analysis were also used to confirm the potential biofilm
      activity of amylase enzyme. The CLSM analysis showed the inhibition of complete
      biofilm formation on amylase enzyme treated glass surface. Further in vivo
      toxicity analysis of amylase enzyme was determined against marine organisms
      Dioithona rigida and Artemia salina. The results showed that there is no
      morphological changes were observed due to the minimal toxicity of amylase
      enzyme. Overall these findings suggested that marine bacterial derived amylase
      enzyme could be developed as potential antibiofilm agent.

PMID- 29454828
TI  - Evaluation of alpha-glucosidase inhibiting potentials with docking calculations
      of synthesized arylidene-pyrazolones.
AB  - Herein, condensation of aryl(hetaryl)pyrazole-4-carbaldehydes 1(a-c) with
      substituted pyrazolones 2(a-d) lead to the corresponding arylidene-pyrazolones
      3(a-l) which were tested against alpha-glucosidase enzyme. The synthesized
      compounds displayed moderate to good activity. Among these, a coumarin derivative
      3k exhibited excellent results (IC50 2.10 +/- 0.004 uM) in comparison to clinical
      drug acarbose (IC50 37.38 +/- 0.12 uM). The ligand-protein interactions were
      identified through docking and stabilizing energy calculations.

PMID- 29454829
TI  - Bioactive triterpenoids from twigs of Betula schmidtii.
AB  - Investigation of the MeOH extract of Betula schmidtii twigs resulted in the
      isolation and identification of three new triterpenoids (1-3), along with ten
      known ones (4-13). The structures of new compounds (1-3) were elucidated by
      spectroscopic methods, including 1D, 2D NMR (1H and 13C NMR, COSY, HSQC, HMBC,
      and NOESY), HR-MS, and chemical methods. All the isolated compounds were
      evaluated for their cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell
      lines. Compound 11 exhibited potent cytotoxic activities against four cell lines,
      and compounds 5 and 13 significantly induced nerve growth factor secretion in a
      C6 rat glioma cell line. Their anti-inflammatory effects were also assessed by
      measuring nitric oxide production in lipopolysaccharide-activated BV-2 cells.
      Compounds 7 and 12 displayed potent inhibition of nitric oxide production,
      without significant cell toxicity.

PMID- 29454830
TI  - The discrepancy function of NLRC5 isoforms in antiviral and antibacterial immune
      responses.
AB  - NOD-like receptors (NLRs) are a family of intracellular pattern recognition
      receptors (PRRs) that play critical roles in innate immunity against pathogens
      infection. NLRC5, the largest member of NLR family, has been characterized as a
      regulator of innate immunity and MHC class I expression. Alternative splicing of
      NLRC5 is only reported in human and zebrafish. However, the function of NLRC5
      isoforms in the innate immune responses remains unknown. In the present study, we
      report the functional characterization of zfNLRC5a and zfNLRC5d, two splicing
      isoforms of zebrafish NLRC5. zfNLRC5a and zfNLRC5d are generated by exon
      skipping, and whose alternative splicing sites exist in the region of LRRs.
      Fluorescence microscopy showed that zfNLRC5 isoforms were located throughout the
      entire cell including nuclear staining. The expression of zfNLRC5 isoform was
      inducible in response to bacterial and viral infections. During SVCV infection,
      the in vitro and in vivo studies found that zfNLRC5d overexpression increased
      protection against viral infection; however zfNLRC5a overexpression had no
      significant effect on antiviral activity. Interestingly, zfNLRC5 isoforms but not
      zfNLRC5 were involved in transcriptional regulation of TLRs and NF-kappaB
      signaling. Overexpression of zfNLRC5 isoforms also contributed to negative
      regulation of antibacterial immune response, with the decreased expression of
      nfkbiaa (IkappaBalpha). All together, these results firstly demonstrate the
      function of NLRC5 isoforms in antiviral and antibacterial immune responses both
      in vitro and in vivo.

PMID- 29454831
TI  - Characterisation of major histocompatibility complex class I transcripts in an
      Australian dragon lizard.
AB  - Characterisation of squamate major histocompatibility complex (MHC) genes has
      lagged behind other taxonomic groups. MHC genes encode cell-surface glycoproteins
      that present self- and pathogen-derived peptides to T cells and play a critical
      role in pathogen recognition. Here we characterise MHC class I transcripts for an
      agamid lizard (Ctenophorus decresii) and investigate the evolution of MHC class I
      in Iguanian lizards. An iterative assembly strategy was used to identify six full
      length C. decresii MHC class I transcripts, which were validated as likely to
      encode classical class I MHC molecules. Evidence for exon shuffling recombination
      was uncovered for C. decresii transcripts and Bayesian phylogenetic analysis of
      Iguanian MHC class I sequences revealed a pattern expected under a birth-and
      death mode of evolution. This work provides a stepping stone towards further
      research on the agamid MHC class I region.

PMID- 29454832
TI  - Identification and functional analysis of inhibitor of NF-kappaB kinase (IKK)
      from Scylla paramamosain: The first evidence of three IKKs in crab species and
      their expression profiles under biotic and abiotic stresses.
AB  - IKK (inhibitor of NF-kappaB kinase) is the critical regulator for NF-kappaB
      (nuclear factor-kappaB) pathway against pathogenic invasion in vertebrates or
      invertebrates. However, the IKK from crab species has not yet been identified. In
      the present study, three full-length cDNA sequences of IKKs from mud crab Scylla
      paramamosain, designated as SpIKKbeta, SpIKKepsilon1 and SpIKKepsilon2, were
      firstly cloned through RT-PCR and RACE methods. This is also the first report
      about the identification of two IKKepsilon genes in mud crab and even in
      crustaceans. The SpIKKbeta cDNA was 2824 bp in length with an open reading frame
      (ORF) of 2382 bp, which encoded a putative protein of 793 amino acids (aa). The
      ORF of two SpIKKepsilon isoforms, SpIKKepsilon1 and SpIKKepsilon2, were 2400 bp
      and 2331 bp in length encoding 799 aa and 776 aa, respectively. The crucial
      conserved residues and functional domains, including the kinase domains (KDs) and
      leucine zipper (LZ), were identified in all SpIKKs. Phylogenetic analysis
      suggested that SpIKKbeta was classified into the IKKs class while SpIKKepsilons
      could be grouped into the IKK-related kinases class. The qRT-PCR analysis showed
      that three SpIKKs were constitutively expressed in all tested tissues and the
      highest expression levels of SpIKKbeta and SpIKKepsilons were all in hemocyte.
      The gene expression profiles of SpIKKs were distinct when crabs suffered biotic
      and abiotic stresses including the exposures of Vibrio alginolyticus, poly (I:C),
      cadmium and air exposure, suggesting that the SpIKKs might play different roles
      in response to pathogens infections, heavy metal and air exposure. Moreover, IKKs
      from mud crab can significantly activate mammalian NF-kappaB pathway, suggesting
      the function of IKKs might be evolutionally well-conserved. Results of the RNAi
      experiments suggested that SpIKKs might regulate the immune signaling pathway
      when hemocytes were challenged with V. parahemolyticus or virus-analog poly
      (I:C). All of these results indicated that the obtained SpIKKs might be involved
      in stress responses against biotic or abiotic stresses, and it also highlighted
      their functional conservation in the innate immune system from crustaceans to
      mammals.

PMID- 29454833
TI  - Towards resolving the presynaptic NMDA receptor debate.
AB  - In the classical view, postsynaptic NMDA receptors (NMDARs) trigger Hebbian
      plasticity via Ca2+ influx. However, unconventional presynaptic NMDARs
      (preNMDARs) which regulate both long-term and short-term plasticity at several
      synapse types have also been found. A lack of sufficiently specific experimental
      manipulations and a poor understanding of how preNMDARs signal have contributed
      to long-standing controversy surrounding these receptors. Although several prior
      studies linked preNMDARs to neocortical timing-dependent long-term depression
      (tLTD), a recent study argues that the NMDARs are actually postsynaptic and
      signal metabotropically, that is, without Ca2+. Other recent work indicates that,
      whereas ionotropic preNMDARs signaling controls evoked release, spontaneous
      release is regulated by metabotropic NMDAR signaling. We argue that elucidating
      unconventional NMDAR signaling modes-both presynaptically and metabotropically-is
      key to resolving the preNMDAR debate.

PMID- 29454834
TI  - Functional implications of inhibitory synapse placement on signal processing in
      pyramidal neuron dendrites.
AB  - A rich literature describes inhibitory innervation of pyramidal neurons in terms
      of the distinct inhibitory cell types that target the soma, axon initial segment,
      or dendritic arbor. Less attention has been devoted to how localization of
      inhibition to specific parts of the pyramidal dendritic arbor influences
      dendritic signal detection and integration. The effect of inhibitory inputs can
      vary based on their placement on dendritic spines versus shaft, their distance
      from the soma, and the branch order of the dendrite they inhabit. Inhibitory
      synapses are also structurally dynamic, and the implications of these dynamics
      depend on their dendritic location. Here we consider the heterogeneous roles of
      inhibitory synapses as defined by their strategic placement on the pyramidal cell
      dendritic arbor.

PMID- 29454835
TI  - Mast cells signal their importance in health and disease.
AB  - FcepsilonRI is the primary receptor in mast cells that mediates allergic
      reactions by inducing rapid release of mediators, an adaptive immune response
      that might have evolved as a host defense against parasites and venoms. Yet it is
      apparent that mast cells are also activated through non-IgE receptors, the
      significance of which is just beginning to be understood. This includes the Mas
      related G protein-coupled receptor X2, which might contribute to reactions to
      diverse antimicrobials and polybasic compounds, and the adhesion G protein
      coupled receptor E2, variants of which are associated with familial vibratory
      urticaria and are activated by mechanical vibration. Similarly, mast cells have
      long been recognized as the main repository for histamine, heparin, and
      proteases. Recent evidence also points to new functions, modes of delivery, and
      mechanisms of action of mast cell proteases that add new dimensions to the roles
      of mast cells in human biology. In addition, exposure of mast cells to
      environmental cues can quantitatively and qualitatively modulate their responses
      and thus their effect on allergic inflammation. Illustrating this paradigm, we
      summarize a number of recent studies implicating the injury/tissue damage
      cytokine IL-33 as a modulator of allergen-induced mast cell responses. We also
      discuss the discovery of markers associated with transformed mast cells and new
      potential directions in suppressing mast cell activity.

PMID- 29454837
TI  - Autoimmune neurological disorders-does the age matter?

PMID- 29454838
TI  - Analysis of cocaine adulterants in human brain in cases of drug-related death.
AB  - : For different reasons, street cocaine is often diluted with pharmacologically
      active substances, the so-called adulterants such as levamisole or hydroxyzine. A
      controversial debate exists currently on the uptake of adulterants from cocaine
      preparations and drug-related death. Previous research convincingly argues that
      serious adverse side effects that affect the central nervous and cardiovascular
      systems can be a consequence of adulterated cocaine. AIMS: Having identified the
      presence of adulterants in lung tissue and blood, the concentrations of these
      substances in brain, an important target location, was of interest. This provides
      an opportunity to assess their role in cases of drug-related deaths. MATERIALS
      AND METHODS: We developed and validated a method for the analysis of cocaine, two
      cocaine metabolites and six adulterants, which can typically be found in cocaine
      preparations, and one adulterant metabolite in brain tissue by gas chromatography
      mass spectrometry (GC-MS)1. Ten brain samples which were tested positive for
      cocaine were analyzed. The homogenized brain tissue was embedded into drying
      paper for protein precipitation. During a subsequent solid-phase extraction
      (SPE), the eluate and one of the wash fractions were collected. After
      derivatization with N-Methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) in
      pyridine and isooctane, the extracts were analyzed by GC-MS. RESULTS AND
      DISCUSSION: The method was fully validated for cocaine (COC), benzoylecgonine
      (BZE), ecgonine methyl ester (EME), diltiazem (DIL), hydroxyzine (HYD), and
      levamisole (LEV) and partly validated for cetirizine (CET), lidocaine (LID),
      phenacetin (PHE), and procaine (PRO) in brain material. By analyzing post-mortem
      brain tissue of ten cocaine users, LEV, LID, and HYD as well as PHE were
      identified in contrast to DIL, PRO, and the HYD metabolite CET. HYD and LEV were
      found in moderate to high concentrations in some cases. Therefore, it cannot be
      excluded that they have caused adverse side effects. CONCLUSION: Because
      adulterants can potentially affect the central nervous and cardiac systems, it is
      likely that they enhance COC toxicity.

PMID- 29454836
TI  - Mechanism for initiation of food allergy: Dependence on skin barrier mutations
      and environmental allergen costimulation.
AB  - BACKGROUND: Mechanisms for the development of food allergy in neonates are
      unknown but clearly linked in patient populations to a genetic predisposition to
      skin barrier defects. Whether skin barrier defects contribute functionally to
      development of food allergy is unknown. OBJECTIVE: The purpose of the study was
      to determine whether skin barrier mutations, which are primarily heterozygous in
      patient populations, contribute to the development of food allergy. METHODS: Mice
      heterozygous for the filaggrin (Flg)ft and Tmem79ma mutations were skin
      sensitized with environmental and food allergens. After sensitization, mice
      received oral challenge with food allergen, and then inflammation, inflammatory
      mediators, and anaphylaxis were measured. RESULTS: We define development of
      inflammation, inflammatory mediators, and food allergen-induced anaphylaxis in
      neonatal mice with skin barrier mutations after brief concurrent cutaneous
      exposure to food and environmental allergens. Moreover, neonates of allergic
      mothers have increased responses to suboptimal sensitization with food allergens.
      Importantly, responses to food allergens by these neonatal mice were dependent on
      genetic defects in skin barrier function and on exposure to environmental
      allergens. ST2 blockade during skin sensitization inhibited the development of
      anaphylaxis, antigen-specific IgE, and inflammatory mediators. Neonatal
      anaphylactic responses and antigen-specific IgE were also inhibited by oral pre
      exposure to food allergen, but interestingly, this was blunted by concurrent pre
      exposure of the skin to environmental allergen. CONCLUSION: These studies uncover
      mechanisms for food allergy sensitization and anaphylaxis in neonatal mice that
      are consistent with features of human early-life exposures and genetics in
      patients with clinical food allergy and demonstrate that changes in barrier
      function drive development of anaphylaxis to food allergen.

PMID- 29454839
TI  - Monitoring the extent of vertical and lateral movement of human decomposition
      products through sediment using cholesterol as a biomarker.
AB  - Due to the lack of human decomposition research facilities available in different
      geographical regions, the extent of movement of human decomposition products from
      a cadaver into various sedimentary environments, in different climates, has not
      been able to be studied in detail. In our study, a human cadaver was placed on
      the surface of a designated plot at the Australian Facility for Taphonomic
      Experimental Research (AFTER), the only human decomposition facility in
      Australia, where the natural process of decomposition was allowed to progress
      over 14days in the Australian summer. Sediment columns (approximately 1m deep)
      were collected at lateral distances of 0.25m, 0.5m, 1.0m and 2.5m in each of four
      directions from the centre of the torso. Plot elevation and weather data were
      also collected. Each sediment column was subdivided, dried and homogenised. A
      sample was isolated from each sediment subdivision, extracted with hexane, and
      the hexane extract cleaned with citrate buffer (pH 3), filtered and spiked with
      cholesterol-D7 internal standard. After derivatisation with BSTFA+1% TMCS,
      cholesterol was monitored in the samples using targeted gas chromatography tandem
      mass spectrometry analysis. A positive result for decomposition products was
      given if the cholesterol abundance in the test sample was higher than that
      detected in the 'control' samples of a similar substrate type collected prior to
      cadaver placement. Within the confines of the experimental design and the
      measured parameters, lateral leaching was observed over distances of up to 2.5m
      from the centre of the torso, which was the maximum distance tested in the study.
      Vertical leaching was detected to depths of up to 49cm below the ground surface.
      Such data can aid the development of policies related to plot sizing and sediment
      renewal and regeneration at other human decomposition facilities and at
      cemeteries. The density and distribution of cholesterol surrounding the cadaver
      in this study can also help forensic investigators interpret cases involving
      remains that have been moved or scavenged.

PMID- 29454840
TI  - Melanocortin 4 receptor stimulation improves social deficits in mice through
      oxytocin pathway.
AB  - Several studies on humans and mice support oxytocin's role in improving social
      behaviour, but its use in pharmacotherapy presents some important limiting
      factors. To date, it is emerging a pharmacological potential for melanocortin 4
      receptor (MC4R) agonism in social deficits treatment. Recently, we demonstrated
      that the deletion of the NFKB1 gene, which encodes the p50 NF-kappaB subunit,
      causes impairment in social behaviours, with reductions in social interactions in
      mice. In this work, we tested the acute effects of THIQ, a selective melanocortin
      4 receptor (MC4R) agonist. THIQ treatment increased social interactions both in
      wild type and p50-/- mice. In particular, after treatment with THIQ, p50-/- mice
      showed a prosocial behaviour analogous to that of basal WT mice. Moreover,
      intranasal treatment with an oxytocin antagonist blocked social interactions
      induced by THIQ, demonstrating that its prosocial effects are mediated by the
      oxytocin pathway. The data obtained reinforce using MC4R agonists to ameliorate
      social impairment in NDDs.

PMID- 29454842
TI  - Spatial access to food: Retiring the food desert metaphor.
AB  - The food desert metaphor has been widely used over the past few decades as a way
      to identify regions as being at risk for having little or no access to healthy
      food. While the simplicity of the metaphor is attractive, this article argues
      that its usefulness to researchers interested in understanding the relationship
      between the geography of healthy food opportunities and dietary behaviours is
      limited. More nuanced approaches to incorporating geography into food access
      studies, like including transportation, economic factors, and time use, in
      addition to considering other dimensions of accessibility, are warranted.

PMID- 29454841
TI  - Hypocretin/orexin deficiency decreases cocaine abuse liability.
AB  - Compelling evidence indicates that hypocretin/orexin signaling regulates arousal,
      stress and reward-seeking behaviors. However, most studies on drug reward-related
      processes have so far described the effects of pharmacological blockers
      disrupting hypocretin/orexin transmission. We report here an extensive study on
      cocaine-related behaviors in hypocretin/orexin-deficient mice (KO) and their
      heterozygous (HET) and wildtype (WT) littermates. We evaluated behavioral
      sensitization following repeated administrations and preference for an
      environment repeatedly paired with cocaine injections (15 mg/kg). Mice were also
      trained to self-administer cocaine (0.5-1.5 mg/kg/infusion). Our observations
      show that whereas all mice exhibited quite similar responses to acute
      administration of cocaine, only Hcrt KO mice exhibited reduced cocaine-seeking
      behaviors following a period of abstinence or extinction, and reduced cocaine
      incubation craving. Further, if the present findings confirm that Hcrt deficient
      mice may display a hypoactive phenotype, possibly linked to a reduced alertness
      concomitant to a decreased exploration of their environment, hypocretin/orexin
      defiency did not cause any attentional deficit. We thus report that innate
      disruption of hypocretin/orexin signaling moderately alters cocaine reward but
      significantly reduces long-term affective dependence that may explain the lack of
      relapse for cocaine seeking seen in Hcrt KO mice. Overall, with blunted cocaine
      intake at the highest concentration and reduced responsiveness to cocaine cues
      after prolonged abstinence, our findings suggest that hypocretin deficient mice
      may display signs of resilience to cocaine addiction.

PMID- 29454843
TI  - Impact of high sucrose diets on the discrimination of spatial and object memories
      with overlapping features.
AB  - High sucrose diets (HSDs) have been shown to have detrimental effects on
      hippocampal dependent memory in rats, including the performance of spatial tasks
      reliant on pattern separation, a cognitive process involved in minimising
      interference during memory encoding. As such we sought to investigate the impact
      of HSDs on object and spatial recognition tasks that varied the cognitive load
      placed on pattern separation processes. Young male and female rats were 4 weeks
      old at the start of diet manipulations. Rats in the HSD condition were provided
      with daily access to 10% sucrose solution for 2 h per day across a 28 d period,
      during which they were assessed on their performance of memory tasks that varied
      the similarity of spatial arrangements (Spontaneous Location Recognition, SLR)
      and object features (Novel Object Recognition, NOR) to determine the effect of
      HSD on memory encoding processes. Both female and male rats that consumed HSDs
      were impaired at NOR when objects shared multiple features (s-NOR), however when
      objects were distinct, novel object recognition was not impacted by HSD
      consumption. Male rats in the control condition generally outperformed female
      rats in the SLR task when there were small spatial separations (s-SLR) but not
      when there were large spatial separations (d-SLR). HSD consumption disrupted
      performance of d-SLR in female rats, but not male rats. Specific HSD deficits
      were observed in HSD consuming male rats in the s-SLR task. However, the volume
      of sucrose consumed differed between sexes, and may have impacted memory
      differentially. These findings indicate that HSD-induced memory deficits may
      extend to pattern separation dependent recognition memory mechanisms when objects
      share overlapping features, and impairments in spatial tasks may be more
      pronounced in female rats.

PMID- 29454846
TI  - Comparison of reporting phase III randomized controlled trials of antibiotic
      treatment for common bacterial infections in ClinicalTrials.gov and matched
      publications.
AB  - OBJECTIVES: Discrepancies between ClinicalTrials.gov entries and matching
      publications were previously described in general medicine. We aimed to evaluate
      the consistency of reporting in trials addressing systemic antibiotic therapy.
      METHODS: We searched ClinicalTrials.gov for completed phase III trials comparing
      antibiotic regimens until May 2017. Matched publications were identified in
      PubMed. Two independent reviewers extracted data and identified inconsistencies.
      Reporting was assessed among studies started before and after 1 July 2005, when
      the International Committee of Medical Journal Editors (ICMJE) required mandatory
      registration as a prerequisite for considering a trial for publication. RESULTS:
      Matching publications were identified for 75 (70%) of 107 ClinicalTrials.gov
      entries. Median time from study completion to publication was 26 months
      (interquartile range 19-42). Primary outcome definition was inconsistent between
      ClinicalTrials.gov and publications in seven trials (7/72, 10%) and reporting of
      the primary outcome timeframe was inconsistent in 14 (14/71, 20%). Secondary
      outcomes definitions were inconsistent in 36 trials (36/66, 55%). Reporting of
      inclusion criteria and study timeline were inconsistent in 17% (13/65) and 3%
      (2/65), respectively. Trials started after July 2005 were significantly less
      likely to have reporting inconsistencies and were published in higher impact
      factor journals. CONCLUSIONS: We found a lower inconsistency rate of outcome
      reporting compared with other medical disciplines. Reporting completeness and
      consistency were significantly better after July 2005. The ICMJE requirement for
      mandatory registration was associated with significant improvement in reporting
      quality in infectious diseases trials. Prolonged time lag to publication and
      missing data from unpublished trials should raise a discussion on current
      reporting and publishing procedures.

PMID- 29454845
TI  - Evaluation of a new multiplex PCR assay (ParaGENIE G-Amoeba Real-Time PCR kit)
      targeting Giardia intestinalis, Entamoeba histolytica and Entamoeba
      dispar/Entamoeba moshkovskii from stool specimens: evidence for the limited
      performances of microscopy-based approach for amoeba species identification.
AB  - OBJECTIVES: Besides the potential to identify a wide variety of gastrointestinal
      parasites, microscopy remains the reference standard in clinical microbiology for
      amoeba species identification and, especially when coupled with adhesin
      detection, to discriminate the pathogenic Entamoeba histolytica from its sister
      but non-pathogenic species Entamoeba dispar/Entamoeba moshkovskii. However, this
      approach is time-consuming, requires a high-level of expertise that can be
      jeopardized considering the low prevalence of gastrointestinal parasites in non
      endemic countries. Here, we evaluated the CE-IVD-marked multiplex PCR (ParaGENIE
      G-Amoeba, Ademtech) targeting E. histolytica and E. dispar/E. moshkovskii and
      Giardia intestinalis. METHODS: This evaluation was performed blindly on a
      reference panel of 172 clinical stool samples collected prospectively from 12
      laboratories and analysed using a standardized protocol relying on microscopy
      (and adhesin detection by ELISA for the detection of E. histolytica) including G.
      intestinalis (n = 37), various amoeba species (n = 55) including E. dispar (n =
      15), E. histolytica (n = 5), as well as 17 other gastrointestinal parasites (n =
      80), and negative samples (n = 37). RESULTS: This new multiplex PCR assay offers
      fast and reliable results with appropriate sensitivity and specificity for the
      detection of G. intestinalis and E. dispar/E. moshkovskii from stools
      (89.7%/96.9% and 95%/100%, respectively). Detection rate and specificity were
      greatly improved by the PCR assay, highlighting several samples misidentified by
      microscopy, including false-negative and false-positive results for both E.
      dispar/E. moshkovskii and E. histolytica. CONCLUSION: Given the clinical
      relevance of amoeba species identification, microbiologists should be aware of
      the limitations of using an algorithm relying on microscopy coupled with adhesin
      detection by ELISA.

PMID- 29454844
TI  - The epidemiology of febrile illness in sub-Saharan Africa: implications for
      diagnosis and management.
AB  - BACKGROUND: Fever is among the most common symptoms of people living in Africa,
      and clinicians are challenged by the similar clinical features of a wide spectrum
      of potential aetiologies. AIM: To summarize recent studies of fever aetiology in
      sub-Saharan Africa focusing on causes other than malaria. SOURCES: A narrative
      literature review by searching the MEDLINE database, and recent conference
      abstracts. CONTENT: Studies of multiple potential causes of fever are scarce, and
      for many participants the infecting organism remains unidentified, or multiple co
      infecting microorganisms are identified, and establishing causation is
      challenging. Among ambulatory patients, self-limiting arboviral infections and
      viral upper respiratory infections are common, occurring in up to 60% of children
      attending health centres. Among hospitalized patients there is a high prevalence
      of potentially fatal infections requiring specific treatment. Bacterial
      bloodstream infection and bacterial zoonoses are major causes of fever. In recent
      years, the prevalence of antimicrobial resistance among bacterial isolates has
      increased, notably with spread of extended spectrum beta-lactamase-producing
      Enterobacteriaceae and fluoroquinolone-resistant Salmonella enterica. Among those
      with human immunodeficiency virus (HIV) infection, Mycobacterium tuberculosis
      bacteraemia has been confirmed in up to 34.8% of patients with sepsis, and fungal
      infections such as cryptococcosis and histoplasmosis remain important.
      IMPLICATIONS: Understanding the local epidemiology of fever aetiology, and the
      use of diagnostics including malaria and HIV rapid-diagnostic tests, guides
      healthcare workers in the management of patients with fever. Current challenges
      for clinicians include assessing which ambulatory patients require antibacterial
      drugs, and identifying hospitalized patients infected with organisms that are not
      susceptible to empiric antibacterial regimens.

PMID- 29454847
TI  - Bejel in Cuba: molecular identification of Treponema pallidum subsp. endemicum in
      patients diagnosed with venereal syphilis.
AB  - OBJECTIVES: Bejel, caused by Treponema pallidum subsp. endemicum (TEN), was until
      now considered as a non-venereal disease endemic in areas with hot and dry
      climates. This study has identified TEN in clinical samples from Cuban patients
      previously diagnosed with syphilis. METHODS: We performed sequencing-based
      molecular typing on 92 samples from Cuban individuals diagnosed with syphilis.
      Moreover, to differentiate T. pallidum subspecies, multi-locus sequence analysis
      (MLSA) was designed and was applied to suspicious samples. RESULTS: Nine samples,
      from six patients, had a nucleotide sequence similarity (at all typing loci) to
      the Bosnia A genome, which is the infectious agent of bejel. Additionally, MLSA
      clearly supported a TEN classification for the treponemal samples. Clinical and
      epidemiological data from the six patients also suggested sexual transmission of
      bejel as well as the endemicity of this rare treponematosis in Cuba. CONCLUSIONS:
      Molecular identification of Treponema pallidum subsp. endemicum, the agent of
      bejel, in Cuban patients diagnosed with syphilis indicates the clear limitations
      of a diagnosis based exclusively on serology, geographical occurrence, clinical
      symptoms and anamnestic data. This finding has important implications for Global
      Public Health Systems, including paradigm changes regarding the location of
      endemic outbreaks, clinical aspects and transmission of this neglected disease.

PMID- 29454848
TI  - Multicentre derivation and validation of a simple predictive index for healthcare
      associated Clostridium difficile infection.
AB  - OBJECTIVES: Clostridium difficile infection (CDI) is the most common cause of
      healthcare-associated infections in the United States. Despite well-established
      risk factors, little research has focused on use of these variables to identify a
      patient population at high risk for CDI to target with primary prevention
      strategies. A predictive index for healthcare-associated CDI could improve
      clinical care and guide research for primary prevention trials. Our objective was
      to develop a predictive index to identify patients at high risk for healthcare
      associated CDI. METHODS: We performed a secondary database analysis in a five
      hospital health system in Houston, Texas. Our cohort consisted of 97 130
      hospitalized patients admitted for more than 48 hours between October 2014 and
      September 2016. The derivation cohort consisted of the initial 80% of admissions
      (75 545 patients), with the remainder being used in the validation cohort.
      RESULTS: CDI rates in the derivation and validation cohorts were 1.55% and 1.43%,
      respectively. Thirty-day predictors of CDI were increased number of high-risk
      antibiotics, Charlson comorbidity index score, age and receipt of a proton pump
      inhibitor. These variables were incorporated into a simple risk index with a
      score range of 0 to 10. The final model demonstrated good discrimination and
      calibration with the observed CDI incidence ranging from 0.1% to 20.4%.
      CONCLUSIONS: We developed a predictive index for 30-day risk of healthcare
      associated CDI using readily available and clinically useful variables. This
      simple predictive risk index may be used to improve clinical decision making and
      resource allocation for CDI stewardship initiatives, and guide research design.

PMID- 29454849
TI  - ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus
      Document on the safety of targeted and biological therapies: an infectious
      diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR
      inhibitors).
AB  - BACKGROUND: The present review is part of the European Society of Clinical
      Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in
      Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and
      biologic therapies. AIMS: To review, from an infectious diseases perspective, the
      safety profile of therapies targeting different intracellular signaling pathways
      and to suggest preventive recommendations. SOURCES: Computer-based Medline
      searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT:
      Although BCR-ABL tyrosine kinase inhibitors modestly increase the overall risk of
      infection, dasatinib has been associated with cytomegalovirus and hepatitis B
      virus reactivation. BRAF/MEK kinase inhibitors do not significantly affect
      infection susceptibility. The effect of Bruton tyrosine kinase inhibitors
      (ibrutinib) among patients with B-cell malignancies is difficult to distinguish
      from that of previous immunosuppression. However, cases of Pneumocystis jirovecii
      pneumonia (PCP), invasive fungal infection and progressive multifocal
      leukoencephalopathy have been occasionally reported. Because phosphatidylinositol
      3-kinase inhibitors (idelalisib) may predispose to opportunistic infections, anti
      Pneumocystis prophylaxis and prevention strategies for cytomegalovirus are
      recommended. No increased rates of infection have been observed with venetoclax
      (antiapoptotic protein Bcl-2 inhibitor). Therapy with Janus kinase inhibitors
      markedly increases the incidence of infection. Pretreatment screening for chronic
      hepatitis B virus and latent tuberculosis infection must be performed, and anti
      Pneumocystis prophylaxis should be considered for patients with additional risk
      factors. Cancer patients receiving mTOR inhibitors face an increased incidence of
      overall infection, especially those with additional risk factors (prior therapies
      or delayed wound healing). IMPLICATIONS: Specific preventive approaches are
      warranted in view of the increased risk of infection associated with some of the
      reviewed agents.

PMID- 29454850
TI  - Dissemination of Panton-Valentine leukocidin-positive methicillin-resistant
      Staphylococcus aureus USA300 clone in multiple hospitals in Tokyo, Japan.
AB  - OBJECTIVES: Panton-Valentine leukocidin (PVL) gene (lukS/F-PV)-positive community
      acquired methicillin-resistant Staphylococcus aureus (MRSA), particularly the
      USA300 clone, is a health concern worldwide. Recently, community-acquired MRSA
      clones have been found to spread and persist in hospital settings. We aimed to
      investigate the prevalence and molecular epidemiologic features of lukS/F-PV
      positive MRSA in Japanese hospitals. METHODS: A total of 3433 MRSA isolated from
      nine hospitals in 2011-2015 were assessed. Molecular epidemiologic analysis
      performed by staphylococcal cassette chromosome mec typing, PVL typing, arginine
      catabolic mobile element typing, detection of virulence determinants, multilocus
      sequence typing, pulsed-field gel electrophoresis and antimicrobial
      susceptibility testing. RESULTS: The detection rate of lukS/F-PV was increased
      annually from 0.6% (5/817) in 2011 to 3.1% (17/544) in 2015. Molecular
      epidemiologic analysis for 64 lukS/F-PV-positive MRSA isolates revealed that 42
      isolates (65.6%) were the USA300 clone. Resistance rates of levofloxacin and
      gentamicin among lukS/F-PV-positive isolates increased annually as a result of
      increased prevalence of the multidrug-resistant USA300 clone. CONCLUSIONS: This
      is the first report on dissemination of the USA300 clone and PVL-positive MRSA in
      multiple Japanese hospitals. Our data strongly suggest that the USA300 clone may
      become epidemic in Japanese hospitals.

PMID- 29454851
TI  - Declines in adult blood lead levels in New York City compared with the United
      States, 2004-2014.
AB  - OBJECTIVES: To assess changes in lead exposure in the New York City (NYC) adult
      population over a 10-year period and to contrast changes with national estimates,
      overall, and by socio-demographics and smoking status. METHODS: We used
      measurements of blood lead levels (BLLs) from NYC resident adults who
      participated in the NYC Health and Nutrition Examination Surveys (HANES) in 2004
      and 2013-2014. We compared estimates of geometric means (GM), 95th percentiles,
      and prevalence of BLL >= 5 ug/dL overall and by subgroups over time, with adults
      who participated in the National HANES (NHANES) 2001-2004 and 2011-2014. RESULTS:
      The GM BLLs among NYC adults declined from 1.79 ug/dL in 2004 to 1.13 ug/dL in
      2013-2014 (P < .0001). The declines over this period ranged from 30.1% to 43.2%
      across socio-demographic groups and smoking status (P < .0001 for all
      comparisons), and were slightly greater than declines observed nationally. The
      drop in prevalence of elevated BLLs (>= 5 ug/dL) was also greater in NYC (4.8
      0.5%), compared with NHANES (3.8-2.0%). By 2013-2014, NYC adults with lower
      annual family income (< $20,000) no longer had higher GM BLLs relative to those
      with higher incomes (>= $75,000), a disparity improvement not observed
      nationally. Likewise, GM BLLs and 95th percentiles for non-Hispanic black adults
      in NYC were lower than GM BLLs for non-Hispanic white adults. Non-Hispanic Asian
      adults had the highest GM BLLs compared with other racial/ethnic groups, both in
      NYC in 2013-14 and nationally in 2011-2014 (1.37 ug/dL, P = .1048 and 1.22 ug/dL,
      P = .0004, respectively). CONCLUSION: The lessening of disparity in lead exposure
      across income groups and decreasing exposure at the high end of the distribution
      among non-Hispanic black and Asian adults in NYC suggest that regulatory and
      outreach efforts have effectively targeted these higher exposure risk groups.
      However, Asian adults still had the highest average BLL, suggesting a need for
      enhanced outreach to this group. Local surveillance remains an important tool to
      monitor BLLs of local populations and to inform initiatives to reduce exposures
      in those at highest risk.

PMID- 29454852
TI  - Chronic exposure to inhaled, traffic-related nitrogen dioxide and a blunted
      cortisol response in adolescents.
AB  - BACKGROUND: Chronic health effects of traffic-related air pollution, like
      nitrogen dioxide (NO2), are well-documented. Animal models suggested that NO2
      exposures dysregulate cortisol function. OBJECTIVES: We evaluated the association
      between traffic-related NO2 exposure and adolescent human cortisol
      concentrations, utilizing measures of the cortisol diurnal slope. METHODS: 140
      adolescents provided repeated salivary cortisol samples throughout one day. We
      built a land use regression model to estimate chronic NO2 exposures based on home
      and school addresses. We then generated model-based estimates of the association
      between cortisol and NO2 exposure one year prior to cortisol sampling, examining
      changes in cortisol diurnal slope. The final model was adjusted other criteria
      pollutants, measures of psychosocial stress, anthropometry, and other demographic
      and covariates. RESULTS: We observed a decrease in diurnal slope in cortisol for
      adolescents exposed to the estimated 75th percentile of ambient NO2 (high
      exposure) relative to those exposed at the 25th percentile (low exposure). For a
      highly exposed adolescent, the log cortisol was lower by 0.06 ug/dl at waking
      (95% CI: -0.15, 0.02), 0.07 ug/dl at 30 min post waking (95% CI: -0.15, 0.02),
      and higher by 0.05 ug/dl at bedtime (95% CI: 0.05, 0.15), compared to a low
      exposed adolescent. For an additional interquartile range of exposure, the model
      based predicted diurnal slope significantly decreased by 0.12 (95% CI: -0.23, 
      0.01). CONCLUSIONS: In adolescents, we found that increased, chronic exposure to
      NO2 and the mixture of pollutants from traffic sources was associated with a
      flattened diurnal slope of cortisol, a marker of an abnormal cortisol response
      which we hypothesize may be a mechanism through which air pollution may affect
      respiratory function and asthma in adolescents.

PMID- 29454853
TI  - The photoprotective and anti-inflammatory activity of red propolis extract in
      rats.
AB  - The negative effects triggered by ultraviolet radiation, such as premature aging
      and carcinogenesis, have motivated several studies on photoprotection. Recent
      strategies for photoprotection have included the incorporation of natural
      antioxidant and anti-inflammatory compounds, such as flavonoids, into sunscreens
      and the oral administration of natural antioxidant extracts. Brazilian Red
      propolis extract contains isoflavonoids with antioxidant and anti-inflammatory
      activities. Here, we investigate the photoprotective effects of orally- or
      topically-administered formulations containing hydroalcoholic extract of red
      propolis (HERP) in a rodent model. HERP showed markers identified as: daidzein
      (4.68 MUg/mL), formononetin (31.81 MUg/mL) and biochanin A (9.58 MUg/mL). A
      fourth peak was found in the chromatogram but was not identified. The antioxidant
      activity of HERP was calculated to be 3.07 mmol Trolox/g and 2.13 mmol Trolox/g,
      respectively. Topical HERP exerted a protective action against UVB radiation,
      which was similar to that exerted by oxybenzone filter. Oral HERP as an adjuvant
      treatment did not increase sunburn protection. However, the oral administration
      of HERP presented chemoprotective and anti-inflammatory activity (p < 0.05)
      similar or better than Polypodium leucotomos oral treatment (positive control).
      In conclusion, topical administration of HERP has photoprotective activity in a
      murine model and the mechanisms of protection can be related to the antioxidant
      and anti-inflammatory characteristics of HERP compounds.

PMID- 29454854
TI  - ERK1/2 inhibitors: New weapons to inhibit the RAS-regulated RAF-MEK1/2-ERK1/2
      pathway.
AB  - The RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is de-regulated in a
      variety of cancers due to mutations in receptor tyrosine kinases (RTKs), negative
      regulators of RAS (such as NF1) and core pathway components themselves (RAS,
      BRAF, CRAF, MEK1 or MEK2). This has driven the development of a variety of
      pharmaceutical agents to inhibit RAF-MEK1/2-ERK1/2 signalling in cancer and both
      RAF and MEK inhibitors are now approved and used in the clinic. There is now much
      interest in targeting at the level of ERK1/2 for a variety of reasons. First,
      since the pathway is linear from RAF-to-MEK-to-ERK then ERK1/2 are validated as
      targets per se. Second, innate resistance to RAF or MEK inhibitors involves
      relief of negative feedback and pathway re-activation with all signalling going
      through ERK1/2, validating the use of ERK inhibitors with RAF or MEK inhibitors
      as an up-front combination. Third, long-term acquired resistance to RAF or MEK
      inhibitors involves a variety of mechanisms (KRAS or BRAF amplification, MEK
      mutation, etc.) which re-instate ERK activity, validating the use of ERK
      inhibitors to forestall acquired resistance to RAF or MEK inhibitors. The first
      potent highly selective ERK1/2 inhibitors have now been developed and are
      entering clinical trials. They have one of three discrete mechanisms of action -
      catalytic, "dual mechanism" or covalent - which could have profound consequences
      for how cells respond and adapt. In this review we describe the validation of
      ERK1/2 as anti-cancer drug targets, consider the mechanism of action of new
      ERK1/2 inhibitors and how this may impact on their efficacy, anticipate factors
      that will determine how tumour cells respond and adapt to ERK1/2 inhibitors and
      consider ERK1/2 inhibitor drug combinations.

PMID- 29454855
TI  - Signalling pathways regulating galactosaminoglycan synthesis and structure in
      vascular smooth muscle: Implications for lipoprotein binding and atherosclerosis.
AB  - Atherosclerosis commences with the trapping of low density lipoproteins (LDLs) in
      blood vessels by modified proteoglycans (PGs) with hyperelongated
      glycosaminoglycan (GAG) chains. GAG chain synthesis and growth factor mediated
      hyperelongation regulates the composition and size of PGs in a manner that would
      cause low density lipoprotein (LDLs) retention in vessel wall.
      Galactosaminoglycans are a class of GAGs, commonly observed on PGs. Multiple
      enzymes are involved in galactosaminoglycan biosynthesis. Galactosaminoglycan
      synthesis is regulated by various signalling pathways which are amenable to
      pharmacological manipulation to treat atherosclerosis. Receptor mediated
      signalling pathways including protein tyrosine kinase receptors (PTKRs),
      serine/threonine kinase receptors (S/TKRs) and G-protein coupled receptors
      (GPCRs) pathways regulate galactosaminoglycan synthesizing enzyme expression.
      Increased expression of these enzymes modify galactosaminoglycan chain structure
      by making them hyperelongated. This review focuses on the signalling pathways
      regulating the expression of genes involved in galactosaminoglycan synthesis and
      modification. Furthermore, there are multiple other processes for inhibiting the
      interactions between LDL and galactosaminoglycans such as peptide mimetics of
      ApoB100 and anti-galactosaminoglycan antibodies and the therapeutic potential of
      these strategies is also addressed.

PMID- 29454856
TI  - Nucleosidic DNA demethylating epigenetic drugs - A comprehensive review from
      discovery to clinic.
AB  - DNA methylation plays a pivotal role in the etiology of cancer by mediating
      epigenetic silencing of cancer-related genes. Since the relationship between
      aberrant DNA methylation and cancer has been understood, there has been an
      explosion of research at developing anti-cancer therapies that work by inhibiting
      DNA methylation. From the discovery of first DNA hypomethylating drugs in the
      1980s to recently discovered second generation pro-drugs, exceedingly large
      number of studies have been published that describe the DNA hypomethylation-based
      anti-neoplastic action of these drugs in various stages of the pre-clinical
      investigation and advanced stages of clinical development. This review is a
      comprehensive report of the literature published in past 40 years, on so far
      discovered nucleosidic DNA methylation inhibitors in chronological order. The
      review will provide a complete insight to the readers about the mechanisms of
      action, efficacy to demethylate and re-express various cancer-related genes, anti
      tumor activity, cytotoxicity profile, stability, and bioavailability of these
      drugs. The review further presents the far known mechanisms of primary and
      secondary resistance to azanucleoside drugs. Finally, the review highlights the
      ubiquitous role of DNA hypomethylating epi-drugs as chemosensitizers and/or
      priming agents, and recapitulate the combinatorial cancer preventive effects of
      these drugs with other epigenetic agents, conventional chemo-drugs, or
      immunotherapies. This comprehensive review analyzes the beneficial
      characteristics and drawbacks of nucleosidic DNA methylation inhibitors, which
      will assist the pre-clinical and clinical researchers in the design of future
      experiments to improve the therapeutic efficacy of these drugs and circumvent the
      challenges in the path of successful epigenetic therapy.

PMID- 29454858
TI  - Expression of heat shock protein 70 and cell death kinetics after different
      thermal impacts on cultured retinal pigment epithelial cells.
AB  - Recent technologies are broadening the possibility to treat the retinal pigment
      epithelium (RPE) with different thermal impacts, from sublethal to lethal ranges.
      Thus temperature-dependent subcellular molecular responses need to be elucidated
      in more detail. In this study, RPE cell viability and expression of heat shock
      protein 70 (Hsp70) were investigated after thermal irradiation with different
      temperature increase using an in-vitro model. Primary porcine RPE cell cultures
      were irradiated with different laser power of a thulium laser (lambda = 1940 nm,
      beam-diameter 30 mm) for 10 s, such that the maximal temperatures at the center
      of the culture dish (Tmax) reach 40, 44, 47, 51 or 59  degrees C after 10-s
      irradiation. The temperature distribution across the culture dish shows a
      Gaussian decay from central position to the periphery of the dish. At 3, 24 and
      48 h after irradiation cell viability was assessed with fluorescence microscopy
      using cell viability-indicating fluorescence dyes, followed by the determination
      of the threshold temperature for apoptotic change and death of RPE cells.
      Intracellular localization and amount of Hsp70 were investigated with
      immunofluorescence and western blotting, respectively. The threshold temperature
      (at the 10th second of irradiation: T10s) for cellular apoptosis and complete
      cell death showed a decrease over time after irradiation, suggesting a long-term
      process of thermally induced cell death. For complete cell death the threshold
      T10s was 52.1 +/- 0.6  degrees C, 50.1 +/- 1.4  degrees C, and 50.1 +/- 0.8 
      degrees C, for 3, 24 and 48 h, respectively, whereas for the apoptotic changes
      48.6 +/- 1.8  degrees C, 47.2 +/- 1.3  degrees C, and 46.7 +/- 0.9  degrees C,
      respectively. Quantitative analysis of Hsp70 with western blotting showed a
      significant increase in intracellular Hsp70 at lethal irradiation with Tmax >= 51
      degrees C, up to 19.6 +/- 2.3 fold after 48 h at 59  degrees C, whereas sub
      lethal irradiations with Tmax <= 44  degrees C led to a slight tendency of time
      dependent increases (up to 1.8 +/- 1.1 fold) over 48 h. Immunostainings for Hsp70
      showed a circle- or ring-pattern of the Hsp70 staining during 3-48 h after
      irradiation, and the range of the 1st and 3rd quartiles of T10s for heat-induced
      Hsp70 expression over this time period was between 44.8  degrees C and 48.2 
      degrees C. A very strong staining of Hsp70 was observed at the border to the
      damaged zone, where many cells show the strong staining in the whole cytoplasmic
      space, while some cells in the nucleus, or some cells show the signs of cell
      migration and proliferation. Moreover, among the cells showing high intensity of
      Hsp70 staining, there are small round cells like apoptotic cells. Results suggest
      that RPE cell death after thermal irradiation may take time, and mostly undergoes
      through apoptosis, unless cells are immediately killed. Thermal irradiation
      induced Hsp70 expression is not only temperature-dependent, but also depends
      largely on the existence of neighboring cell death, suggesting the crucial role
      of Hsp70 in apoptosis and wound healing processes of RPE cells. The increase of
      Hsp70 over 24-48 h indicates its long-term roles in cell responses both after
      sublethal and lethal thermal laser irradiations.

PMID- 29454857
TI  - Distinct CD40L receptors mediate inflammasome activation and secretion of IL
      1beta and MCP-1 in cultured human retinal pigment epithelial cells.
AB  - CD40L signaling occurs in several diseases with inflammatory components,
      including ocular and retinal diseases. However, it has never been evaluated as a
      pathogenic mechanism in age-related macular degeneration (AMD) or as an inducer
      of inflammasome formation in any cell type. mRNA and protein levels of CD40, IL
      1beta, NALP1, NALP3, caspase-1, and caspase-5 were determined by RT-PCR, qPCR,
      and Western blot. CD40L receptor (CD40, alpha5beta1, and CD11b) expression was
      determined by Western and immunofluorescent staining. IL-1beta, IL-18, and MCP-1
      secretions were determined by ELISA. NALP1 and NALP3 inflammasome formation were
      determined by Co-IP. Experiments were conducted on primary human retinal pigment
      epithelial (hRPE) cells from four different donors. Human umbilical vein
      endothelial (HUVEC) and monocytic leukemia (THP-1) cells demonstrated the general
      applicability of our findings. In hRPE cells, CD40L-induced NALP1 and NALP3
      inflammasome activation, cleavage of caspase-1 and caspase-5, and IL-1beta and IL
      18 secretion. Interestingly, neutralizing CD11b and alpha5beta1 antibodies, but
      not CD40, reduced CD40L-induced IL-1beta secretion in hRPE cells. Similarly,
      CD40L treatment also induced HUVEC and THP-1 cells to secret IL-1beta through
      CD11b and alpha5beta1. Additionally, the CD40L-induced IL-1beta secretion acted
      in an autocrine/paracrine manner to feed back and induce hRPE cells to secrete
      MCP-1. This study is the first to show that CD40L induces inflammasome activation
      in any cell type, including hRPE cells, and that this induction is through CD11b
      and alpha5beta1 cell-surface receptors. These mechanisms likely play an important
      role in many retinal and non-retinal diseases and provide compelling drug targets
      that may help reduce pro-inflammatory processes.

PMID- 29454860
TI  - Velocity landscape correlation resolves multiple flowing protein populations from
      fluorescence image time series.
AB  - Molecular, vesicular and organellar flows are of fundamental importance for the
      delivery of nutrients and essential components used in cellular functions such as
      motility and division. With recent advances in fluorescence/super-resolution
      microscopy modalities we can resolve the movements of these objects at higher
      spatio-temporal resolutions and with better sensitivity. Previously, spatio
      temporal image correlation spectroscopy has been applied to map molecular flows
      by correlation analysis of fluorescence fluctuations in image series. However, an
      underlying assumption of this approach is that the sampled time windows contain
      one dominant flowing component. Although this was true for most of the cases
      analyzed earlier, in some situations two or more different flowing populations
      can be present in the same spatio-temporal window. We introduce an approach,
      termed velocity landscape correlation (VLC), which detects and extracts multiple
      flow components present in a sampled image region via an extension of the
      correlation analysis of fluorescence intensity fluctuations. First we demonstrate
      theoretically how this approach works, test the performance of the method with a
      range of computer simulated image series with varying flow dynamics. Finally we
      apply VLC to study variable fluxing of STIM1 proteins on microtubules connected
      to the plasma membrane of Cystic Fibrosis Bronchial Epithelial (CFBE) cells.

PMID- 29454859
TI  - Tauroursodeoxycholic acid binds to the G-protein site on light activated
      rhodopsin.
AB  - The heterotrimeric G-protein binding site on G-protein coupled receptors remains
      relatively unexplored regarding its potential as a new target of therapeutic
      intervention or as a secondary site of action by the existing drugs.
      Tauroursodeoxycholic acid bears structural resemblance to several compounds that
      were previously identified to specifically bind to the light-activated form of
      the visual receptor rhodopsin and to inhibit its activation of transducin. We
      show that TUDCA stabilizes the active form of rhodopsin, metarhodopsin II, and
      does not display the detergent-like effects of common amphiphilic compounds that
      share the cholesterol scaffold structure, such as deoxycholic acid. Computer
      docking of TUDCA to the model of light-activated rhodopsin revealed that it
      interacts using similar mode of binding to the C-terminal domain of transducin
      alpha subunit. The ring regions of TUDCA made hydrophobic contacts with loop 3
      region of rhodopsin, while the tail of TUDCA is exposed to solvent. The results
      show that TUDCA interacts specifically with rhodopsin, which may contribute to
      its wide-ranging effects on retina physiology and as a potential therapeutic
      compound for retina degenerative diseases.

PMID- 29454861
TI  - Methods of reconstitution to investigate membrane protein function.
AB  - Membrane proteins are notoriously difficult to investigate in isolation. The
      focus of this chapter is the key step following extraction and purification of
      membrane proteins; namely reconstitution. The process of reconstitution re
      inserts proteins into a lipid bilayer that partly resembles their native
      environment. This native environment is vital to the stability of membrane
      proteins, ensuring that they undergo vital conformational transitions and
      maintain optimal interaction with their substrates. Reconstitution may take many
      forms and these have been classified into two broad categories. Symmetric systems
      enable unfettered access to both sides of a bilayer. Compartment containing
      systems contain a lumen and are ideally suited to measurement of transport
      processes. The investigator is encouraged to ascertain what aspects of protein
      function will be undertaken and to apply the most advantageous reconstitution
      system or systems. It is important to note that the process of reconstitution is
      not subject to defined protocols and requires empirical optimisation to specific
      targets.

PMID- 29454862
TI  - Fluorescence lifetime correlation spectroscopy: Basics and applications.
AB  - This chapter presents a concise introduction into the method of Fluorescence
      Lifetime Correlation Spectroscopy (FLCS). This is an extension of Fluorescence
      Correlation Spectroscopy (FCS) that analyses fluorescence intensity fluctuations
      from small detection volumes in samples of ultra-low concentration. FCS has been
      widely used for investigating diffusion, conformational changes, molecular
      binding/unbinding equilibria, or chemical reaction kinetics, at single molecule
      sensitivity. In FCS, this is done by calculating intensity correlation curves for
      the measured intensity fluctuations. FLCS extends this idea by calculating
      fluorescence-lifetime specific intensity correlation curves. Thus, FLCS is the
      method of choice for all studies where a parameter of interest (conformational
      state, spatial position, molecular environmental condition) is connected with a
      change in the fluorescence lifetime. After presenting the theoretical and
      experimental basis of FLCS, the chapter gives an overview of its various
      applications.

PMID- 29454864
TI  - Inactivation of Escherichia coli and Staphylococcus aureus on contaminated
      perilla leaves by Dielectric Barrier Discharge (DBD) plasma treatment.
AB  - This study focused on sterilization methods for the reduction of microorganisms
      on perilla leaves by cylinder type Dielectric Barrier Discharge (DBD) plasma with
      underwater bubbler treatment. S. aureus and E. coli in a suspension were reduced
      to less than 3.4 and 0.5 log CFU/ml after the plasma treatment for 3 min,
      respectively. On the perilla leaves, they were also reduced to 4.8 and 1.6 log
      CFU/ml after the plasma treatment, respectively. The S. aureus and E. coli
      bacterial cell wall was damaged by the plasma treatment evident by scanning
      electron microscopic analysis. The observed infrared bands of the FTIR spectra
      demonstrated changes in protein, lipid, polysaccharide, polyphosphate group and
      other carbohydrate functionalities of plasma treated bacteria and untreated
      bacterial cell membranes. The degradation of the constituent bonds of the
      bacterial cell membrane by RONS generated from plasma destroys the DNA, RNA, and
      proteins within the cell, and may eventually cause cell death. In this study,
      H2O2 (13.68 MUM) and NO3 (138 MUM), which are the main factors generated by
      plasma, proved to have a bactericidal effect by inducing lipid peroxidation of
      bacterial cell membranes. In conclusion, cylinder type DBD plasma with underwater
      bubbler can be used as an environmentally friendly food disinfection device in
      cleaning processes of the food industry.

PMID- 29454863
TI  - Potentially Functional Variants of ATG16L2 Predict Radiation Pneumonitis and
      Outcomes in Patients with Non-Small Cell Lung Cancer after Definitive
      Radiotherapy.
AB  - INTRODUCTION: Autophagy not only plays an important role in the progression of
      cancer but is also involved in tissue inflammatory response. However, few
      published studies have investigated associations between functional genetic
      variants of autophagy-related genes and radiation pneumonitis (RP) as well as
      clinical outcomes in patients with NSCLC after definitive radiotherapy. METHODS:
      We genotyped nine potentially functional single-nucleotide polymorphisms (SNPs)
      in four autophagy-related genes (autophagy related 2B gene [ATG2B], autophagy
      related 10 gene [ATG10], autophagy related 12 gene [ATG12], and autophagy related
      16 like 2 gene [ATG16L2]) in 393 North American patients with NSCLC treated by
      definitive radiotherapy and assessed their associations with RP, local recurrence
      free survival (LRFS), progression-free survival (PFS), and overall survival (OS)
      in multivariable Cox proportional hazard regression analyses. RESULTS: We found
      that patients with the ATG16L2 rs10898880 CC variant genotype had a better LRFS,
      PFS, and OS (adjusted hazard ratio = 0.59, 0.64, and 0.64; 95% confidence
      interval: 0.45-0.79, 0.48-0.84, and 0.48-0.86; p = 0.0004, 0.002, and 0.003,
      respectively), but a greater risk for development of severe RP (adjusted hazard
      ratio = 1.80, 95% confidence interval: 1.04-3.12, p = 0.037) than did patients
      with AA/AC genotypes. Further functional analyses suggested that the ATG16L2
      rs10898880 C variant allele modulated expression of the ATG16L2 gene. CONCLUSION:
      This is the first report that one potentially functional SNP rs10898880 in
      ATG16L2 may be a predictor of RP, LRFS, PFS, and OS in patients with NSCLC after
      definitive radiotherapy. Additional larger, prospective studies are needed to
      confirm these findings.

PMID- 29454865
TI  - Inhibitory effects of selenium on cadmium-induced cytotoxicity in PC12 cells via
      regulating oxidative stress and apoptosis.
AB  - Purpose of this study is to investigate mechanism/s of cyto-protection by
      selenium (Na2SeO3; Se4+) against cadmium (CdCl2; Cd2+)-induced cytotoxicity using
      PC12 cells. In addition, Se (5, 10, 20 and 40 MUM) and Cd (2.5, 5 and 10 MUM)
      induced cytotoxicity is determined. Cytotoxicity assays and western blot analyses
      confirmed that Se (>=10 MUM) promotes autophagic cell death via inhibition of
      mTOR activation and p62 accumulation due to increase of cellular oxidative
      stress. On the other hand, co-presence of non-toxic Se (5 MUM) and toxic Cd (5
      MUM) showed to increase cell viability, glutathione and glutathione peroxidase 1
      (GPx1) levels, and to decrease DNA fragmentation and lactate dehydrogenase (LDH)
      activity compared to Cd-treated (5 MUM) cells alone. Furthermore, western blot
      analyses of cytochrome c and ERK1 indicated that Cd-induced apoptotic cell death
      in PC12 cells. However, the co-exposure of Se with Cd significantly decreases the
      release of cytochrome c into cytosol from mitochondria, and up-regulates ERK1
      protein to inhibit Cd-induced apoptosis. In conclusion, Se (>=10 MUM) possess
      cytotoxicity in PC12 cells; however, co-presence of Se (5 MUM) with Cd (5 MUM)
      protects against Cd-induced apoptosis in PC12 cells due to inhibition of Cd
      induced oxidative stress and subsequently suppression of mitochondrial apoptosis
      pathway.

PMID- 29454866
TI  - Behavioral toxicity of sodium cyanide following oral ingestion in rats: Dose
      dependent onset, severity, survival, and recovery.
AB  - Sodium cyanide (NaCN) is a commonly and widely used industrial and laboratory
      chemical reagent that is highly toxic. Its availability and rapid harmful/lethal
      effects combine to make cyanide a potential foodborne/waterborne intentional
      poisoning hazard. Thus, laboratory studies are needed to understand the dose
      dependent progression of toxicity/lethality following ingestion of cyanide
      poisoned foods/liquids. We developed an oral-dosing method in which a standard
      pipette was used to dispense a sodium cyanide solution into the cheek, and the
      rat then swallowed the solution. Following poisoning (4-128 mg/kg), overt toxic
      signs were recorded and survival was evaluated periodically up to 30 hours
      thereafter. Toxic signs for NaCN doses higher than 16 mg/kg progressed quickly
      from head burial and mastication, to lethargy, convulsions, gasping/respiratory
      distress, and death. In a follow-on study, trained operant-behavioral performance
      was assessed immediately following cyanide exposure (4-64 mg/kg) continuously for
      5 h and again the following day. Onset of behavioral intoxication (i.e.,
      behavioral suppression) occurred more rapidly and lasted longer as the NaCN dose
      increased. This oral-consumption method with concomitant operantbehavioral
      assessment allowed for accurate dosing and quantification of intoxication onset,
      severity, and recovery, and will also be valuable in characterizing similar
      outcomes following varying medical countermeasure drugs and doses.

PMID- 29454867
TI  - Acellular filtrate of a microbial-based cleaning product potentiates house dust
      mite allergic lung inflammation.
AB  - Microbial-based cleaning products (MBCPs) contain bacteria and chemical
      constituents. They are used in consumer applications such as odor reduction,
      unclogging drains, and surface cleaning. To determine the capacity of a model
      MBCP to contribute to acute allergic lung inflammation, a two-week repeated
      exposure regimen was used. Mice were exposed by endotracheal instillation to
      saline alone, MBCP alone, house dust mites (HDM) alone, or sequentially (i.e.,
      MBCP followed by HDM, HDM followed by MBCP, or HDM + MBCP followed by HDM). Both
      whole MBCP and acellular MBCP filtrate were investigated, and showed minimal
      differences in the endpoints examined. HDM exposure caused pulmonary perivascular
      inflammation, bronchiolar mucous cell metaplasia, elevated bronchoalveolar lavage
      fluid (BALF) eosinophils, and HDM-specific IgG1. For MBCP, notable changes were
      associated with sequential exposures. MBCP/HDM caused elevated TH2 cytokines in
      BALF, and elevated neutrophils, eosinophils and IL-5 in peripheral blood. Co
      administration of MBCP and HDM followed by HDM resulted in elevated blood and
      BALF eosinophils and HDM-specific IgE and IgG1. These results demonstrated that
      acellular MBCP filtrate, and not bacteria within MBCPs, potentiated the acute
      allergic inflammation to HDM. This methodology could be extended to investigate
      chronic allergic inflammation and inflammatory potential of other MBCPs and
      biotechnology products with complex compositions.

PMID- 29454868
TI  - Halophytic herbs of the Mediterranean basin: An alternative approach to health.
AB  - Wild native species are usually grown under severe and stressful conditions,
      while a special category includes halophytic species that are tolerant to high
      salinity levels. Native halophytes are valuable sources of bioactive molecules
      whose content is higher in saline than normal conditions, since the adaptation to
      salinity mechanisms involve apart from changes in physiological functions the
      biosynthesis of protectant molecules. These compounds include secondary
      metabolites with several beneficial health effects which have been known since
      ancient times and used for medicinal purposes. Recent trends in pharmaceutical
      industry suggest the use of natural compounds as alternative to synthetic ones,
      with native herbs being strong candidates for this purpose due to their increased
      and variable content in health promoting compounds. In this review, an
      introductory section about the importance of native herbs and halophyte species
      for traditional and modern medicine will be presented. A list of the most
      important halophytes of the Mediterranean basin will follow, with special focus
      on their chemical composition and their reported by clinical and
      ethnopharmacological studies health effects. The review concludes by suggesting
      future requirements and perspectives for further exploitation of these valuable
      species within the context of sustainability and climate change.

PMID- 29454869
TI  - The intrapartum and perinatal risks of sleep-disordered breathing in pregnancy: a
      systematic review and metaanalysis.
AB  - OBJECTIVE DATA: Sleep-disordered breathing is an increasingly common condition in
      nonobstetric populations and is associated with significant morbidity. The
      incidence of sleep-disordered breathing in pregnancy is unknown, and it is likely
      that many cases go undiagnosed. STUDY: A systematic review and metaanalysis was
      undertaken to determine whether pregnant women who receive a diagnosis of sleep
      disordered breathing are more likely to have adverse intrapartum and perinatal
      outcomes compared with control subjects. STUDY APPRAISAL AND SYNTHESIS METHODS:
      PubMed, Embase, and Cinahl databases were searched for full-text publications in
      English of sleep-disordered breathing and human pregnancy up to June 2017. Only
      studies that reported on sleep-disordered breathing in relation to gestational
      age or birthweight at delivery, preterm birth, mode of delivery, cord pH, Apgar
      score, nursery admission, stillbirth or perinatal death, meconium at delivery, or
      wound complications were included. RESULTS: A total of 1576 results were
      identified; 33 studies met inclusion criteria. Women with sleep-disordered
      breathing were older (mean difference, 1.66; 95% confidence interval, 1.04-2.28)
      and had a higher body mass index (mean difference, 3.31; 95% confidence interval,
      2.30-4.32) than those who did not. Maternal sleep-disordered breathing was
      associated significantly with preterm birth (<37 weeks gestation; odds ratio,
      1.86; 95% confidence interval, 1.50-2.31) and low birthweight (<2500 g; odds
      ratio, 1.67; 95% confidence interval, 1.00-2.78). These women were also less
      likely to have a vaginal delivery (odds ratio, 0.61; 95% confidence interval,
      0.48-0.78) and to be at a higher risk of having an assisted vaginal delivery
      (odds ratio, 1.88; 95% confidence interval, 1.10-3.21) or a cesarean delivery
      (odds ratio, 1.81; 95% confidence interval, 1.55-2.11). The risk of both elective
      (odds ratio, 1.38; 95% confidence interval, 1.09 - 1.76) and emergency cesarean
      (odds ratio, 2.52; 95% confidence interval, 1.20-5.29) was increased. In
      addition, women with sleep-disordered breathing were at a higher risk of having
      an infant with a 5-minute Apgar score <7 (odds ratio, 2.14; 95% confidence
      interval, 1.24-3.71), stillbirth or perinatal death (odds ratio, 2.02; 95%
      confidence interval, 1.25-3.28), and neonatal nursery admission (odds ratio,
      1.90; 95% confidence interval, 1.38-2.61). CONCLUSION: Maternal sleep-disordered
      breathing is associated with increased risks of adverse intrapartum and perinatal
      outcomes.

PMID- 29454870
TI  - Levator ani defect severity and its association with enlarged hiatus size,
      levator bowl depth, and prolapse size.

PMID- 29454871
TI  - Maternal and neonatal outcomes after bariatric surgery; a systematic review and
      meta-analysis: do the benefits outweigh the risks?
AB  - OBJECTIVE DATA: Obesity during pregnancy is associated with a number of adverse
      obstetric outcomes that include gestational diabetes mellitus, macrosomia, and
      preeclampsia. Increasing evidence shows that bariatric surgery may decrease the
      risk of these outcomes. Our aim was to evaluate the benefits and risks of
      bariatric surgery in obese women according to obstetric outcomes. STUDY: We
      performed a systematic literature search using MEDLINE, Embase, Cochrane, Web of
      Science, and PubMed from inception up to December 12, 2016. Studies were included
      if they evaluated patients who underwent bariatric surgery, reported subsequent
      pregnancy outcomes, and compared these outcomes with a control group. STUDY
      APPRAISAL AND SYNTHESIS METHODS: Two reviewers extracted study outcomes
      independently, and risk of bias was assessed with the use of the Newcastle-Ottawa
      Quality Assessment Scale. Pooled odds ratios for each outcome were estimated with
      the Dersimonian and Laird random effects model. RESULTS: After a review of 2616
      abstracts, 20 cohort studies and approximately 2.8 million subjects (8364 of whom
      had bariatric surgery) were included in the metaanalysis. In our primary
      analysis, patients who underwent bariatric surgery showed reduced rates of
      gestational diabetes mellitus (odds ratio, 0.20; 95% confidence interval, 0.11
      0.37, number needed to benefit, 5), large-for-gestational-age infants (odds
      ratio, 0.31; 95% confidence interval, 0.17-0.59; number needed to benefit, 6),
      gestational hypertension (odds ratio, 0.38; 95% confidence interval, 0.19-0.76;
      number needed to benefit, 11), all hypertensive disorders (odds ratio, 0.38; 95%
      confidence interval, 0.27-0.53; number needed to benefit, 8), postpartum
      hemorrhage (odds ratio, 0.32; 95% confidence interval, 0.08-1.37; number needed
      to benefit, 21), and caesarean delivery rates (odds ratio, 0.50; 95% confidence
      interval, 0.38-0.67; number needed to benefit, 9); however, group of patients
      showed an increase in small-for-gestational-age infants (odds ratio, 2.16; 95%
      confidence interval, 1.34-3.48; number needed to harm, 21), intrauterine growth
      restriction (odds ratio, 2.16; 95% confidence interval, 1.34-3.48; number needed
      to harm, 66), and preterm deliveries (odds ratio, 1.35; 95% confidence interval,
      1.02-1.79; number needed to harm, 35) when compared with control subjects who
      were matched for presurgery body mass index. There were no differences in rates
      of preeclampsia, neonatal intensive care unit admissions, stillbirths,
      malformations, and neonatal death. Malabsorptive surgeries resulted in a greater
      increase in small-for-gestational-age infants (P=.0466) and a greater decrease in
      large-for-gestational-age infants (P=<.0001) compared with restrictive surgeries.
      There were no differences in outcomes when we used administrative databases vs
      clinical charts. CONCLUSION: Although bariatric surgery is associated with a
      reduction in the risk of several adverse obstetric outcomes, there is a potential
      for an increased risk of other important outcomes that should be considered when
      bariatric surgery is discussed with reproductive-age women.

PMID- 29454872
TI  - Simultaneous formation of 3-deoxy-d-threo-hexo-2-ulose and 3-deoxy-d-erythro-hexo
      2-ulose during the degradation of d-glucose derived Amadori rearrangement
      products: Mechanistic considerations.
AB  - Analyzing classical model reaction systems of Amadori rearrangement products
      (ARP) it became apparent that the formation of 3-deoxy-d-threo-hexo-2-ulose (3
      deoxygalactosone, 3-DGal) during the degradation of ARPs is highly dependent on
      pH and the amino acid residue of the respective ARP. Based on a detailed analysis
      of the NMR chemical shifts of the sugar moieties of different ARPs, it could be
      derived that the formation of 3-DGal is sensitive to the stability of a co
      operative hydrogen bond network which involves HO-C3, the deprotonated carboxyl
      functionality and the protonated amino nitrogen of the amino acid substituent.
      Participating in this bond network, HO-C3 is partially protonated which
      facilitates the elimination of water at C3. Based on that, a new mechanism of 3
      deoxyglycosone formation is proposed.

PMID- 29454873
TI  - Strategies for implementing a multiple patient simulation scenario.
AB  - Nursing students often care for one or two patients during hospital clinical
      experiences, while under the supervision of a nurse educator. In this setting,
      students have limited opportunities to make clinical judgments, prioritize, and
      delegate while caring for multiple patients. Research supports the need for
      students to have increased experiences in caring for multiple patients. The aim
      of this paper is to examine the effectiveness of a multiple patient simulated
      clinical experience (SCE) on senior students' perception of their readiness to
      transition to practice. There were 214 senior nursing student participants in
      this mixed methods embedded design study. Following a multiple patient SCE all
      participants completed a self-report survey designed to measure essential
      competencies for transition to practice. Qualitative data in the form of written
      comments were also collected. Essential competencies for transition to practice
      were defined as decision making skills, interprofessional communication, and
      level of preparedness. Quantitative and qualitative data indicated that students
      perceived increased levels of confidence in their readiness to transition to
      practice following the multiple patient SCE. The study revealed an innovative
      teaching-learning strategy that can assist educators with preparing nursing
      students to care for multiple complex patients.

PMID- 29454874
TI  - Stressors for Spanish nursing students in clinical practice.
AB  - BACKGROUND: Clinical practice is critical for nursing students to acquire the
      knowledge and skills needed to properly develop professionally. The presence of
      stress in clinical practice may negatively affect their training. OBJECTIVES: To
      understand the extent to which clinical practice can be stressful for nursing
      students at a Spanish university and to determine the main stressors associated
      with the practice. DESIGN: Cross-sectional, descriptive, and observational study
      conducted in 2016 at the two nursing colleges of the University of Oviedo,
      located in Oviedo and Gijon in the Principality of Asturias, Spain. METHODS: A
      total of 450 nursing students at a Spanish university served as participants in
      this study from January to April 2016. A data collection sheet was developed to
      track different sociodemographic variables, and was distributed together with the
      KEZKAK questionnaire, a validated scale adapted to Spanish nursing students. It
      is composed of 41 items using a 4-point Likert scale, rating how much the
      described situation worries them from 0 ("Not at all") to 3 ("A lot"). RESULTS:
      Students were most concerned about issues relating to causing harm to patients
      and lack of competence. Women found clinical practice to be more stressful than
      men did, both in general terms (p < 0.001) and with respect to all individual
      factors included in the questionnaire. In addition, there were associations
      between the "lack of competence" factor and having a job simultaneously (p =
      0.011), the "contact with suffering" factor and the school year (p = 0.018), and
      the "being harmed by the relationship with patients" factor and the age group (p
      = 0.013). CONCLUSIONS: Nursing students, particularly women, see clinical
      practice as "rather stressful", with the main stressors being those related to
      causing harm to patients.

PMID- 29454875
TI  - Does the level of emotional intelligence affect the degree of success in nursing
      studies?
AB  - BACKGROUND: Emotional intelligence (EI) reflects the general capacity to
      comprehend emotions (in ourselves and in others), to regulate emotions, and to
      cope effectively with emotional situations. The study program in nursing is
      varied, and includes theoretical and practical aspects, but teaching EI is not
      part of the core curriculum. We argue that teaching EI should not only be
      included in the curriculum, but that EI tests should be included in the
      admissions process. OBJECTIVE: This study reviews the relationship between EI
      level and the degree of success in nursing studies, and its importance.
      PARTICIPANTS: A convenience sample of 110 academic nursing students was examined.
      METHODS: Three data collection methods were employed: 1) A socio-demographic
      questionnaire; 2) Schutte Self-Report Inventory (SSRI); 3) Psychometric scores
      and grade transcripts. RESULTS: A positive correlation between the level of EI
      and the degree of success in nursing studies among nursing students was found. EI
      levels improved during the second year of learning. Among nursing students, the
      annual average grade was related to emotional intelligence rather than
      psychometric scores at the time of admission. CONCLUSION: There is a need to
      increase the importance of EI in the terms of nursing student's admission and
      basic nursing curriculums.

PMID- 29454876
TI  - The development and psychometric validation of an instrument to evaluate nurses'
      attitudes towards communication with the patient (ACO).
AB  - BACKGROUND: Patient communication is a key skill for nurses involved in clinical
      care. Its measurement is a complex phenomenon that can be addressed through
      attitude evaluation. OBJECTIVES: To develop and psychometrically test a measure
      of nurses' attitudes towards communication with patients (ACO), to study the
      relationship between these dimensions, and to analyse nursing attitudes. DESIGN:
      To develop and psychometrically test the ACO questionnaire. SETTINGS: All
      hospitals in the province of Valencia were invited by e-mail to distribute the
      ACO instrument. Ten hospitals took part in the study. PARTICIPANTS: The study
      population was composed of a convenience sample of 400 hospital nurses on general
      or special services. The inclusion criteria were nurses at the selected centres
      who had previously provided an informed consent to participate. METHODS: A
      literature review and expert consultation (N = 10) was used to develop the
      content of the questionnaire. The 62-item version of the instrument was applied
      to a convenience sample of 400 nurses between May 2015 and March 2016. Factor
      structure was evaluated with exploratory and confirmatory factor analysis (EFA,
      CFA), and reliability was evaluated with Cronbach's alpha, composite reliability
      (CR), and average variance extracted (AVE). RESULTS: The final instrument (ACO),
      composed of 25 items grouped into three attitude dimensions (cognitive, affective
      and behavioural), had good psychometric properties. In the study sample, nurses
      had a favourable attitude towards communication. The cognitive and affective
      dimensions of the ACO should be able to predict the behaviour dimension.
      CONCLUSION: The ACO is useful for evaluating current clinical practices,
      identifying educational needs and assessing the effectiveness of communication
      training or other interventions intended to improve communication.

PMID- 29454877
TI  - Egyptian and Jordanian nurse educators' perception of barriers preventing the
      implementation of evidence-based practice: A cross-sectional study.
AB  - BACKGROUND: Studies discussing nurse educators' attitudes, knowledge/skills,
      practicing of evidence-based practice (EBP) and barriers encountered towards
      implementation is somewhat limited. OBJECTIVE: The study aimed to identify the
      attitudes, perceived knowledge/skills, and implementation of evidence-based as
      perceived by nurse educators, in Egyptian and Jordanian universities, and to
      assess factors preventing them from adopting it in nursing program.
      DESIGN/SETTING/RESPONDENTS/METHODS: A cross-sectional design was conducted
      including two groups from Egypt and Jordan. Two questionnaires: (i) The Evidence
      Based Practice Questionnaire (EBPQ) and (ii) The Developing Evidence-Based
      Practice Questionnaire (DEBPQ) and a demographic data sheet were used. Data were
      analyzed using SPSS version 20 and descriptive and inferential statistics
      tabulated. RESULTS: Majority of the respondents (85.5%) were females, <40 years
      old (62.1%), and from medical-surgical nursing departments (49.2%). The mean
      score of EBPQ was 4.96 +/- standard deviation 0.91. Frequency of practicing EBP
      and attitudes toward EBP scores were similar between nurse educators in both
      countries (p > 0.05). However, the Jordanian staff had a remarkably higher
      perceived knowledge/skills of EBP than their Egyptian counterparts (Mean Rank =
      79.98 & 57.63 respectively, at p = 0.004). There was a statistically significant
      positive, moderate correlation between attitudes, knowledge/skills and frequency
      of practicing EBP among nurse educators in both countries. The highest
      correlation observed for attitudes and frequency of practicing EBP was among
      Jordanian staff (r = 0.707, p < 0.000). Egyptian nurse educators had
      significantly higher perceived barriers to finding and reviewing evidence than
      their Jordanian counterparts (p = 0.000). However, both groups had similar
      perceived barriers related to changing practice and support from colleagues.
      CONCLUSIONS: Egyptian and Jordanian nurse educators, equally, hold positive
      attitudes toward adopting EBP. However, they encounter many barriers to implement
      it.

PMID- 29454878
TI  - A comorbidity of CF in need of our attention and activity: Attention Deficit
      Hyperactivity Disorder!

PMID- 29454879
TI  - Application of genetically encoded redox biosensors to measure dynamic changes in
      the glutathione, bacillithiol and mycothiol redox potentials in pathogenic
      bacteria.
AB  - Gram-negative bacteria utilize glutathione (GSH) as their major LMW thiol.
      However, most Gram-positive bacteria do not encode enzymes for GSH biosynthesis
      and produce instead alternative LMW thiols, such as bacillithiol (BSH) and
      mycothiol (MSH). BSH is utilized by Firmicutes and MSH is the major LMW thiol of
      Actinomycetes. LMW thiols are required to maintain the reduced state of the
      cytoplasm, but are also involved in virulence mechanisms in human pathogens, such
      as Staphylococcus aureus, Mycobacterium tuberculosis, Streptococcus pneumoniae,
      Salmonella enterica subsp. Typhimurium and Listeria monocytogenes. Infection
      conditions often cause perturbations of the intrabacterial redox balance in
      pathogens, which is further affected under antibiotics treatments. During the
      last years, novel glutaredoxin-fused roGFP2 biosensors have been engineered in
      many eukaryotic organisms, including parasites, yeast, plants and human cells for
      dynamic live-imaging of the GSH redox potential in different compartments.
      Likewise bacterial roGFP2-based biosensors are now available to measure the
      dynamic changes in the GSH, BSH and MSH redox potentials in model and pathogenic
      Gram-negative and Gram-positive bacteria. In this review, we present an overview
      of novel functions of the bacterial LMW thiols GSH, MSH and BSH in pathogenic
      bacteria in virulence regulation. Moreover, recent results about the application
      of genetically encoded redox biosensors are summarized to study the mechanisms of
      host-pathogen interactions, persistence and antibiotics resistance. In
      particularly, we highlight recent biosensor results on the redox changes in the
      intracellular food-borne pathogen Salmonella Typhimurium as well as in the Gram
      positive pathogens S. aureus and M. tuberculosis during infection conditions and
      under antibiotics treatments. These studies established a link between ROS and
      antibiotics resistance with the intracellular LMW thiol-redox potential. Future
      applications should be directed to compare the redox potentials among different
      clinical isolates of these pathogens in relation to their antibiotics resistance
      and to screen for new ROS-producing drugs as promising strategy to combat
      antimicrobial resistance.

PMID- 29454880
TI  - Fluorescence and chemiluminescence approaches for peroxynitrite detection.
AB  - In the last two decades, there has been a significant advance in understanding
      the biochemistry of peroxynitrite, an endogenously-produced oxidant and
      nucleophile. Its relevance as a mediator in several pathologic states and the
      aging process together with its transient character and low steady-state
      concentration, motivated the development of a variety of techniques for its
      unambiguous detection and estimation. Among these, fluorescence and
      chemiluminescence approaches have represented important tools with enhanced
      sensitivity but usual limited specificity. In this review, we analyze selected
      examples of molecular probes that permit the detection of peroxynitrite by
      fluorescence and chemiluminescence, disclosing their mechanism of reaction with
      either peroxynitrite or peroxynitrite-derived radicals. Indeed, probes have been
      divided into 1) redox probes that yield products by a free radical mechanism, and
      2) electrophilic probes that evolve to products secondary to the nucleophilic
      attack by peroxynitrite. Overall, boronate-based compounds are emerging as
      preferred probes for the sensitive and specific detection and quantitation.
      Moreover, novel strategies involving genetically-modified fluorescent proteins
      with the incorporation of unnatural amino acids have been recently described as
      peroxynitrite sensors. This review analyzes the most commonly used fluorescence
      and chemiluminescence approaches for peroxynitrite detection and provides some
      guidelines for appropriate experimental design and data interpretation, including
      how to estimate peroxynitrite formation rates in cells.

PMID- 29454881
TI  - Curcumin treatment leads to better cognitive and mood function in a model of Gulf
      War Illness with enhanced neurogenesis, and alleviation of inflammation and
      mitochondrial dysfunction in the hippocampus.
AB  - Diminished cognitive and mood function are among the most conspicuous symptoms of
      Gulf War Illness (GWI). Our previous studies in a rat model of GWI have
      demonstrated that persistent cognitive and mood impairments are associated with
      substantially declined neurogenesis, chronic low-grade inflammation, increased
      oxidative stress and mitochondrial dysfunction in the hippocampus. We tested the
      efficacy of curcumin (CUR) to maintain better cognitive and mood function in a
      rat model of GWI because of its neurogenic, antiinflammatory, antioxidant, and
      memory and mood enhancing properties. Male rats were exposed daily to low doses
      of GWI-related chemicals, pyridostigmine bromide, N,N-diethyl-m-toluamide (DEET)
      and permethrin, and 5-minutes of restraint stress for 28 days. Animals were next
      randomly assigned to two groups, which received daily CUR or vehicle treatment
      for 30 days. Animals also received 5'-bromodeoxyuridine during the last seven
      days of treatment for analysis of neurogenesis. Behavioral studies through object
      location, novel object recognition and novelty suppressed feeding tests performed
      sixty days after treatment revealed better cognitive and mood function in CUR
      treated GWI rats. These rats also displayed enhanced neurogenesis and diminished
      inflammation typified by reduced astrocyte hypertrophy and activated microglia in
      the hippocampus. Additional studies showed that CUR treatment to GWI rats
      enhanced the expression of antioxidant genes and normalized the expression of
      multiple genes related to mitochondrial respiration. Thus, CUR therapy is
      efficacious for maintaining better memory and mood function in a model of GWI.
      Enhanced neurogenesis, restrained inflammation and oxidative stress with
      normalized mitochondrial respiration may underlie better memory and mood function
      mediated by CUR treatment.

PMID- 29454882
TI  - 1,5-Dimethylhexylamine (octodrine) in sports and weight loss supplements: Natural
      constituent or synthetic chemical?
AB  - In the past years, there has been a mounting trend toward the addition of
      sympathomimetic stimulants in sports and weight loss supplements sold in the US
      and claimed to be from natural constituents. The latest among those
      pharmaceutical stimulants is 1,5-dimethylhexylamine (1,5-DMHA or octodrine), an
      ingredient in newly introduced sports and weight loss supplements with its
      'natural' origin being cited from Aconitum or Kigelia plants. In order to
      validate the natural existence of 1,5-DMHA, two GC/MS methods were developed. One
      method involved using thick film megabore capillary columns to analyze the
      underivatized 1,5-DMHA. The second method was to determine enantiomeric
      distribution of 1,5-DMHA. Fifteen Aconitum or Kigelia plant samples originating
      from various locations were analyzed, and none of them contained 1,5-DMHA within
      the limit of detection (25 ng/mL) of the method. In contrast, although 1,5-DMHA
      was listed on the labels or website for all the 13 dietary supplements, only four
      products were found to contain this compound, with the highest quantity being
      reported as 112 mg per serving size. This is equivalent to more than three times
      the highest pharmaceutical dose established in Europe. The enantiomeric ratios of
      1,5-DMHA in these products were determined to be between 0.9-1.0 (expressed as
      peak area ratio of one enantiomer over another), suggesting racemic nature.
      Interestingly, two byproducts from 1,5-DMHA synthesis were identified in
      commercial supplements containing 1,5-DMHA, indicating that 1,5-DMHA indeed
      originated from a poor quality source. Overall, the significant amount of 1,5
      DMHA observed in the supplements, the enantiomeric distribution and the presence
      of the synthetic byproducts all suggested the synthetic origin of 1,5-DMHA in the
      commercial products.

PMID- 29454883
TI  - Obesity or diet? Levels and determinants of phthalate body burden - A case study
      on Portuguese children.
AB  - In this study we analyzed one of the most comprehensive sets of 21 urinary
      phthalate metabolites representing exposure to 11 parent phthalates (DEP, DMP,
      DiBP, DnBP, BBzP, DEHP, DiNP, DiDP, DCHP, DnPeP, DnOP) in first morning urine
      samples of 112 Portuguese children (4-18 years) sampled in 2014/15. The study
      population consisted of two groups: group 1 with normal weight/underweight
      children (N = 43) following their regular diet and group 2 with obese/overweight
      children (N = 69) following a healthy diet (with nutritional counselling). Most
      of the metabolites were above the limits quantification (81-100%) except for
      MCHP, MnPEP and MnOP. Metabolite levels were generally comparable to other recent
      child and general populations sampled worldwide, confirming the steady decline in
      exposures to most phthalates. Compared to Portuguese children sampled in
      2011/2012, median urinary metabolite levels decreased by approximately 50% for
      DEHP, DnBP, DiBP and BBzP. Risk assessments for individual phthalates and the sum
      of the anti-androgenic phthalates did not indicate to attributable health risks,
      also at the upper percentiles of exposure. In the healthy diet group the median
      concentration of the DEHP metabolites was significant lower, while all phthalate
      metabolites except MEP tended to be lower compared to the regular diet group.
      Multiple log-linear regression analyses revealed significantly lower daily
      intakes (DIs) for all phthalates in the healthy diet group compared to the
      regular diet group (geometric mean ratios (gMR) between 0.510-0.618; p <= 0.05),
      except for DEP (gMR: 0.811; p = 0.273). The same analyses with the continuous
      variable body mass index instead of the diet groups also showed effects on the
      DIs (gMRs between 0.926-0.951; p <= 0.05), however much smaller than the effects
      of the diet. The results indicate that obese children following a healthy diet
      composed of fresh and less packaged/processed food can considerably reduce their
      intake for most phthalates and can have lower phthalate intakes than regular
      weight/regular diet children.

PMID- 29454885
TI  - Attending to identity cues reduces the own-age but not the own-race recognition
      advantage.
AB  - Adults' ability to recognize individual faces is shaped by experience. Young
      adults recognize own-age and own-race faces more accurately than other-age and
      other-race faces. The own-age and own-race biases have been attributed to
      differential perceptual experience and to differences in how in-group vs. out
      group faces are processed, with in-group faces being processed at the individual
      level and out-group faces being processed at the categorical level. To examine
      this social categorization hypothesis, young adults studied young and older faces
      in Experiment 1 and own- and other-race faces in Experiment 2. During the
      learning phase the identity-matching group viewed faces in pairs and completed a
      same/different task designed to enhance attention to individuating cues; the
      passive-viewing group memorized faces presented individually. After the learning
      phase, all participants completed an identical old/new recognition task. Both
      passive-viewing groups showed the expected recognition bias, but divergent
      patterns were observed in the identity-matching groups. Whereas the identity
      matching task eliminated the own-age bias, it neither eliminated nor reduced the
      own-race bias. Collectively, these results suggest that categorization
      individuation processes do not play the same role in explaining the two
      recognition biases.

PMID- 29454884
TI  - Illusory edges comingle with real edges in the neural representation of objects.
AB  - The visual system must transform a point-by-point biological representation from
      the photoreceptors into neural representations of separate objects. Even a
      uniform circular patch of light that slowly modulates in luminance can be
      segmented into separate central and surrounding areas merely by introducing black
      lines to outline a central square. The black lines cause brightness induction in
      the center even though the light inside and outside the square is always
      identical, as predicted by spatial antagonism between the square central area and
      its surround. Importantly, illusory Kanizsa lines forming the square are as
      effective for this brightness induction as real black lines, suggesting a 'form
      cue invariant' cortical neural representation that does not distinguish between a
      central region set off by real or illusory edges. An open question is whether
      separate subsystems generate objects defined by real versus illusory edges, each
      providing the same form-cue invariant neural representation of an object, or
      whether form-cue invariance extends to integrating component pieces that together
      define an object. Experiments here show object segmentation when subparts of a
      square are defined by a mixture of real and illusory edges. Subjects adjusted the
      Michelson contrast of a separate patch to match the perceived modulation depth
      within the central region of a circular field that slowly oscillated in
      luminance. A closed, four-sided figure, no matter how constructed, reduced the
      perceived modulation depth within the central region. This shows that both real
      and illusory subparts can be integrated to segment center from surround. It
      supports a strong version of form-cue invariance in which neural mechanisms
      responsible for object segmentation are impartial to the piecemeal cues that are
      integrated to define an object.

PMID- 29454886
TI  - Development of neuropathology following soman poisoning and medical
      countermeasures.
AB  - Nerve agent-induced seizures can cause varying degrees of neuropathology
      depending on level of poisoning and duration of seizing. The intention of this
      review was to validate a novel approach for establishing effective treatment
      regimens against soman poisoning. Identification of seizure controlling sites in
      the forebrain of rats poisoned by soman was made by means of lesions, and the
      anticonvulsive properties of a number of relevant drugs were tested by
      microinfusions into the identified areas. By using these procedures, procyclidine
      emerged as the most potent drug. Its potency was confirmed in systemic studies
      and is further enhanced when combined with levetiracetam. Acute treatment with a
      combination of HI-6, levetiracetam and procyclidine (procyclidine regimen) can
      effectively manage supralethal poisoning by any of the classical nerve agents.
      Extended treatment with the procyclidine regimen is able to terminate residual
      "silent", local epileptiform activity in the severely poisoned rats. Evident
      advantages are seen when the same regimen exerts both powerful anticonvulsant and
      neuroprotectant efficacies. According to the results presented, the new strategy
      for establishing therapies against soman-induced seizures appears to be valid.

PMID- 29454887
TI  - Metabolomic analysis uncovered an association of serum phospholipid levels with
      estrogen-induced mammary tumors in female ACI/Seg rats.
AB  - Estrogen is reported to be involved in mammary tumorigenesis. To unveil metabolic
      signatures for estrogen-induced mammary tumorigenesis, we carried out serum
      metabolomic analysis in an estrogen-induced mammary tumor model, female August
      Copenhagen-Irish/Segaloff (ACI/Seg) rats, using liquid chromatography-mass
      spectrometry. In contrast to the control group, all rats with an implanted 17beta
      estradiol (E2) pellet developed mammary tumors during this experiment. E2
      treatment significantly suppressed body weight gain. But no significant
      differences in food consumption were observed between the two groups, suggesting
      that metabolic alteration depended on E2 treatment. Serum metabolomic analysis
      detected 116 features that were statistically different (p < 0.01) between the
      groups. Quantitation analysis revealed that several phospholipids such as
      phosphatidylcholines and lysophosphatidylcholines (LPCs) were identified as
      significantly different metabolites. E2-treated rat serum stimulated the
      proliferation of human breast cancer MDA-MB-231 cells. In addition, the
      proliferation effect was diminished by pretreating cells with either autotaxin
      inhibitor or antagonist for lysophosphatidic acid receptor whose ligands are
      metabolites of LPCs via autotaxin-mediated hydrolysis. In summary, our results
      suggest that not only are phospholipids potential biomarkers for mammary tumors
      but importantly, LPCs themselves could be associated with E2-induced mammary
      tumorigenesis in female ACI/Seg rats.

PMID- 29454888
TI  - Bioequivalence decision for nanoparticular iron complex drugs for parenteral
      administration based on their disposition.
AB  - Although parenteral iron products have been established to medicinal use decades
      before, their structure and pharmacokinetic properties are not fully
      characterized yet. With its' second reflection paper on intravenous iron-based
      nano-colloidal products (EMA/CHMP/SWP/620008/2012) the European Medicine Agency
      provided an extensive catalogue of methods for quality, non-clinical and
      pharmacokinetic studies for the comparison of nano-sized iron products to an
      originator (EMA, 2015). For iron distribution studies, the reflection paper
      assumed the use of rodents. In our tests, we used a turkey fetus model to
      investigate time dependent tissue concentrations in pharmacological and
      toxicological relevant tissues liver, heart and kidney. We found turkey embryos
      to be a suitable alternative to rodents with high discriminatory sensitivity.
      Clear differences were found between equimolar doses of iron products with
      hydroxyethyl amylopectin, sucrose, dextrane and carboxymaltose shell. A linear
      dose dependency for the tissue accumulation was also demonstrated.

PMID- 29454889
TI  - Evolution of sexual systems and growth habit in Mussaenda (Rubiaceae): Insights
      into the evolutionary pathways of dioecy.
AB  - Dioecy is a rare sexual system that is thought to represent an "evolutionary dead
      end". While many studies have addressed the evolution of dioecy and/or its
      relationship with the evolution of the woody habit, few have explored the
      relationship between dioecy and climbing habit, and their effects on
      diversification rates. Here, we study the evolution of sexual systems and growth
      habit in Mussaenda (Rubiaceae) using a robust phylogeny of the genus based on
      eight plastid regions and a broad sampling of taxa (92 of the 132 species were
      sampled). A time-calibrated tree was constructed to estimate diversification
      rates in different clades and its correlates with focal characters. More
      specifically, we assess evolutionary correlations between dioecy and climbing
      habit and their respective influences on diversification rates. Ancestral
      character state reconstructions revealed that distyly is the most likely
      ancestral state in Mussaenda. Distyly has subsequently given rise to dioecy,
      short-styled floral monomorphism, and long-styled floral monomorphism. Dioecy has
      evolved independently at least four times from distyly, and has reversed to
      homostylous hermaphroditism at least twice, which does not support the
      "evolutionary dead end" hypothesis. A significant correlation between the
      evolution of dioecy and climbing growth form was found in Mussaenda. It is
      possible that a strong association between high net diversification rates and
      dioecy may exist in Mussaenda, but no association was found with climbing habit.

PMID- 29454890
TI  - Compositional accuracy of atom probe tomography measurements in GaN: Impact of
      experimental parameters and multiple evaporation events.
AB  - A systematic study of the biases occurring in the measurement of the composition
      of GaN by Atom Probe Tomography was carried out, in which the role of surface
      electric field and laser pulse intensity has been investigated. Our data confirm
      that the electric field is the main factor influencing the measured composition,
      which exhibits a deficiency of N at low field and a deficiency of Ga at high
      field. The deficiency of Ga at high field is interpreted in terms of preferential
      evaporation of Ga. The detailed analysis of multiple evaporation events reveals
      that the measured composition is not affected by pile-up phenomena occurring in
      detection system. The analysis of correlation histograms yields the signature of
      the production of neutral N2 due to the dissociation of GaN32+ ions. However, the
      amount of N2 neutral molecules that can be detected cannot account for the N
      deficiency found at low field. Therefore, we propose that further mechanisms of
      neutral N evaporation could be represented by dissociation reactions such as GaN+
      > Ga++ N and GaN2+-> Ga2++ N.

PMID- 29454891
TI  - A new procedure for processing extracted teeth for immediate grafting in post
      extraction sockets. An experimental study in American Fox Hound dogs.
AB  - OBJECTIVES: To investigate freshly extracted dental particulate used to graft
      post-extraction sockets in dogs, comparing new bone formation at experimental and
      control sites. MATERIALS AND METHODS: Bilateral premolars P2, P3, P4 and first
      mandibular molars were extracted atraumatically from six American Fox Hound dogs.
      The teeth were ground immediately using a 'Smart Dentin Grinder'. The dentin
      particulate was sieved to ensure a grain size of 300-1200MUm and immersed in an
      alcohol cleanser to dissolve organic debris and bacteria, followed by washing in
      sterile saline buffer solution. The animals were divided into two groups
      randomly: group 'A' (control) samples were left to heal without any extraction
      socket grafting procedure; group 'B' (experimental) sockets were filled with the
      autogenous dentin particulate graft. The rate of tissue healing and the quantity
      of bone formation were evaluated using histological and histomorphometric
      analyses at 60 and 90 days post-grafting. The type of bone generated was
      categorized as woven (immature bone) or lamellar bone (mature bone). RESULTS:
      Substantially more bone formation was found in Group B (experimental) than Group
      A (control) at 60 and 90 days (p<0.05). Less immature bone was identified in the
      dentin grafted group (25.7%) than the control group (55.9%) [corrected]. Similar
      differences were also observed at 90 days post grafting. CONCLUSION: Autogenous
      dentin particulate grafted immediately after extractions may be considered a
      useful biomaterial for socket preservation, protecting both buccal and lingual
      plates, generating large amounts of new woven bone formation after 60 days, and
      small amounts of lamellar bone after 90 days healing.

PMID- 29454892
TI  - Fexaramine as an entry blocker for feline caliciviruses.
AB  - Feline calicivirus (FCV) is a small non-enveloped virus containing a single
      stranded, positive-sense RNA genome of approximately 7.7 kb. FCV is a highly
      infectious pathogen of cats and typically causes moderate, self-limiting acute
      oral and upper respiratory tract diseases or chronic oral diseases. In addition,
      in recent years, virulent, systemic FCV (vs-FCV) strains causing severe systemic
      diseases with a high mortality rate of up to 67% have been reported in cats.
      Although FCV vaccines are commercially available, their efficacy is limited due
      to antigenic diversity of FCV strains and short duration of immunity. In this
      study, we identified fexaramine as a potent inhibitor of FCV including vs-FCV
      strains in cell culture and demonstrated that fexaramine is a entry blocker for
      FCV by using various experiments including time-of-addition studies, generation
      of resistant viruses in cell culture and the reverse genetics system. A
      fexaramine resistant FCV mutant has a single amino acid change in the P2 domain
      of VP1 (the major capsid), and the importance of this mutation for conferring
      resistance was confirmed using the reverse genetics system. A comparative
      analysis of viral resistance was also performed using a peptidyl inhibitor
      (NPI52) targeting FCV 3C-like protease. Finally, the effects of combination
      treatment of fexaramine and NPI52 against FCV replication and emergence of
      resistant viruses were investigated in cell culture.

PMID- 29454893
TI  - Deciphering the growth pattern and phytohormonal content in Saskatoon berry
      (Amelanchier alnifolia) in response to in vitro cytokinin application.
AB  - Clonal propagation plays a critical integral role in the growth and success of a
      global multi-billion dollar horticulture industry through a constant supply of
      healthy stock plants. The supply chain depends on continuously improving the
      micropropagation process, thus, understanding the physiology of in vitro plants
      remains a core component. We evaluated the influence of exogenously applied
      cytokinins (CKs, N6-benzyladenine = BA, isopentenyladenine = iP, meta-topolin =
      mT, 6-(3-hydroxybenzylamino)-9-(tetrahydropyran-2-yl)purine = mTTHP) in Murashige
      and Skoog (MS)-supplemented media on organogenic response and accumulation of
      endogenous CK and indole-3-acetic acid (IAA) metabolites. The highest shoot
      proliferation (30 shoots/explant) was obtained with 20 MUM mT treatment. However,
      the best quality regenerants were produced in 10 MUM mT treatment. Rooting of
      Amelanchier alnifolia in vitro plantlets was observed at the lowest CK
      concentrations, with the highest root proliferation (3 roots/explant) in 1 MUM
      mTTHP regenerants. Similar to the organogenic response, high levels of endogenous
      bioactive CK metabolites (free bases, ribosides, and nucleotides) were detected
      in mT and mTTHP-derived regenerants. The level of O-glucosides was also
      comparatively high in these cultures. All CK-treated plants had high levels of
      endogenous free IAA compared to the control. This may suggest an influence of CKs
      on biosynthesis of IAA.

PMID- 29454894
TI  - Letter to the Editor regarding article "Emerging concepts for the treatment of
      hepatitis delta" [Menashe Elazar and Jeffrey S Glenn, Curr Opin Virol 24 (2017)
      55-59].

PMID- 29454895
TI  - Ensemble coding of face identity is present but weaker in congenital
      prosopagnosia.
AB  - Individuals with congenital prosopagnosia (CP) are impaired at identifying
      individual faces but do not appear to show impairments in extracting the average
      identity from a group of faces (known as ensemble coding). However, possible
      deficits in ensemble coding in a previous study (CPs n = 4) may have been masked
      because CPs relied on pictorial (image) cues rather than identity cues. Here we
      asked whether a larger sample of CPs (n = 11) would show intact ensemble coding
      of identity when availability of image cues was minimised. Participants viewed a
      "set" of four faces and then judged whether a subsequent individual test face,
      either an exemplar or a "set average", was in the preceding set. Ensemble coding
      occurred when matching (vs. mismatching) averages were mistakenly endorsed as set
      members. We assessed both image- and identity-based ensemble coding, by varying
      whether test faces were either the same or different images of the identities in
      the set. CPs showed significant ensemble coding in both tasks, indicating that
      their performance was independent of image cues. As a group, CPs' ensemble coding
      was weaker than controls in both tasks, consistent with evidence that perceptual
      processing of face identity is disrupted in CP. This effect was driven by CPs (n=
      3) who, in addition to having impaired face memory, also performed particularly
      poorly on a measure of face perception (CFPT). Future research, using larger
      samples, should examine whether deficits in ensemble coding may be restricted to
      CPs who also have substantial face perception deficits.

PMID- 29454896
TI  - Functional magnetic resonance imaging of divergent and convergent thinking in Big
      C creativity.
AB  - The cognitive and physiological processes underlying creativity remain unclear,
      and very few studies to date have attempted to identify the behavioral and brain
      characteristics that distinguish exceptional ("Big-C") from everyday ("little-c")
      creativity. The Big-C Project examined functional brain responses during tasks
      demanding divergent and convergent thinking in 35 Big-C Visual Artists (VIS), 41
      Big-C Scientists (SCI), and 31 individuals in a "smart comparison group" (SCG)
      matched to the Big-C groups on parental educational attainment and estimated IQ.
      Functional MRI (fMRI) scans included two activation paradigms widely used in
      prior creativity research, the Alternate Uses Task (AUT) and Remote Associates
      Task (RAT), to assess brain function during divergent and convergent thinking,
      respectively. Task performance did not differ between groups. Functional MRI
      activation in Big-C and SCG groups differed during the divergent thinking task.
      No differences in activation were seen during the convergent thinking task. Big-C
      groups had less activation than SCG in frontal pole, right frontal operculum,
      left middle frontal gyrus, and bilaterally in occipital cortex. SCI displayed
      lower frontal and parietal activation relative to the SCG when generating
      alternate uses in the AUT, while VIS displayed lower frontal activation than SCI
      and SCG when generating typical qualities (the control condition in the AUT). VIS
      showed more activation in right inferior frontal gyrus and left supramarginal
      gyrus relative to SCI. All groups displayed considerable overlapping activation
      during the RAT. The results confirm substantial overlap in functional activation
      across groups, but suggest that exceptionally creative individuals may depend
      less on task-positive networks during tasks that demand divergent thinking.

PMID- 29454897
TI  - Involvement of eIF2alpha of Epinephelus coioides in the fish immune response to
      virus infection.
AB  - The eukaryotic initiation factor 2 alpha subunit (eIF2alpha) is a key translation
      regulator that plays an important role in different cellular pressures and
      stimuli, including virus infection. In the present study, an eIF2alpha homolog
      (EceIF2alpha) from the orange-spotted grouper (Epinephelus coioides) was cloned
      and its roles during fish viral infection were characterized. EceIF2alpha encodes
      a putative protein of 315 amino acid residues, and shares a high degree of
      similarity with eIF2alphas from other species. Quantitative real-time polymerase
      chain reaction (qRT-PCR) analysis indicated that EceIF2alpha was distributed in
      all examined tissues. Both of the expression levels of EceIF2alpha in the spleen
      and head kidney of E. coioides were up-regulated when challenged with polyinosine
      polycytidylic acid (poly[I:C]). EceIF2alpha was abundantly distributed in both
      the cytoplasm and nucleus in grouper spleen (GS) cells. Over-expression of
      EceIF2alpha improved the expression of red-spotted grouper nervous necrosis virus
      (RGNNV) genes in GS cells. In addition, EceIF2alpha depressed the activation of
      NK-kappaB and IFN-beta. Furthermore, dephosphorylation inhibitor treatment led to
      a significant decrease of RGNNV gene transcription. Taken together, these results
      suggest that EceIF2alpha might be involved in the fish immune response to virus
      challenge.

PMID- 29454898
TI  - Dietary values of Forsythia suspensa extract in Penaeus monodon under normal
      rearing and Vibrio parahaemolyticus 3HP (VP3HP) challenge conditions: Effect on
      growth, intestinal barrier function, immune response and immune related gene
      expression.
AB  - Two trials were conducted to determine the effects of dietary Forsythia suspensa
      extract (FSE) on shrimp, Penaeus monodon, first on growth performance, second on
      the immune response and immune related gene expression of shrimp. In trial 1,
      shrimp (mean initial wet weight about 3.02 g) were fed with five diets containing
      0% (basal diet), 0.01%, 0.02%, 0.04% and 0.06% FSE in triplicate for 60 days.
      Growth performance (final body wet weight, FBW; weight gain, WG; biomass gain,
      BG) of shrimp fed FSE diets were higher (P < 0.05) than that of shrimp fed the
      basal diet. The survival among all the diets treatments were above 90% and no
      significant difference was revealed among them (P > 0.05). The antioxidant
      capacity (total antioxidant status, TAS; glutathione peroxidase, GSH-Px) appears
      in the trend of firstly increasing then decreasing with the increasing of dietary
      FSE levels. The highest value of TAS and GSH-Px were found in shrimp fed 0.02%
      FSE diet and were significantly higher than that of shrimp fed the basal and
      0.06% FSE diets (P < 0.05). Hepatopancreas malondialdehyde (MDA) of shrimp fed
      FSE diets were lower (P < 0.05) than that of shrimp fed the basal diet. Total
      haemocyte count of shrimp fed the basal diet was lower (P < 0.05) than that of
      shrimp fed FSE diets. Haemolymph clotting time of shrimp had the opposite trend
      with the total haemocyte count of shrimp. No significant differences were found
      in haemolymph biomarkers of intestinal permeability (endotoxin and diamine
      oxidase) and in molecular gene expression profiles of heat shock protein 70 (Hsp
      70) mRNA and hypoxia inducible factor-1alpha (HIF-1alpha) mRNA in haemolymph of
      shrimp among all diet treatments (P > 0.05). In trial 2, a pathogenic strain of
      Vibrio parahaemolyticus 3HP (VP3HP) injection challenge test was conducted for 6
      day after the rearing trial and shrimp survival were also compared among
      treatments. Survival of shrimp fed diets supplemented with 0.01%-0.02% FSE were
      higher than that of shrimp fed the basal and 0.06% FSE diets (P < 0.05). Dietary
      FSE supplementation produced stronger hepatopancreas antioxidant capacity (TAS,
      GSH-Px) (P < 0.05) and higher glutathione (GSH) level (P < 0.05), lower
      superoxide dismutase activity (SOD) (P < 0.05), higher total haemocyte count (P <
      0.05), lower haemolymph clotting time (P < 0.05), lower MDA and carbonyl protein
      concentration (P < 0.05), lower haemolymph biomarkers of intestinal permeability
      (endotoxin and diamine oxidase) (P < 0.05), generated lower molecular gene
      expression profiles of HSP 70 mRNA and higher HIF-1alpha mRNA (P < 0.05) than the
      basal diet. The immune response were characterized by lower TAS and higher
      antioxidant enzyme activities (SOD, GSH-Px) and higher oxidative stress level
      (MDA and carbonyl protein) and higher haemolymph biomarkers of intestinal
      permeability (endotoxin and diamine oxidase) compared to levels found in trail 1.
      However, the total haemocyte counts and haemolymph clotting times were not
      changed in 0.01%-0.02% FSE diets treatments between trial 1 and trial 2 (P >
      0.05). The molecular gene expression profile of Hsp 70 mRNA was increased while
      HIF-1alpha mRNA was decreased when compared to trial 1. In conclusion, results
      suggested that dietary intake containing FSE could enhance the growth performance
      and antioxidant capacity of P. monodon and furthermore reduce oxidative stress
      and immune depression challenged by a pathogenic strain of Vibrio
      parahaemolyticus stress. Considering the effect of FSE on both growth performance
      and immune response of P. monodon, the level of FSE supplemented in the diet
      should be between 0.01% and 0.02%.

PMID- 29454899
TI  - Cannabis for Vismodegib-Related Muscle Cramps in a Patient With Advanced Basal
      Cell Carcinoma.

PMID- 29454900
TI  - Immunohistochemical investigation of predictors of response or aggressiveness of
      bowen disease after photodynamic therapy.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a good option for the treatment of
      Bowen's disease (BD). However, BD occasionally can progress into a squamous cell
      carcinoma (SCC) after PDT. OBJECTIVE: Find predictors of aggressiveness of BD
      after PDT METHODS: Two biopsies of patients with BD treated with PDT with
      progression to SCC within three months were selected for immunohistochemical
      (IHC) studies. Conventional PDT was applied. IHC analysis was performed together
      with hematoxylin-eosin in the biopsies prior to and after treatment with PDT.
      RESULTS: Among the IHC markers studied, none showed different expressions between
      pre-treatment and post-treatment biopsies except for HSP70 CONCLUSIONS: The
      expression of Hsp70 in BD may predict future aggressive behaviour in BD when
      treated with PDT. Nevertheless, due to the small number of biopsies studied,
      further investigations are required to draw conclusions.

PMID- 29454901
TI  - Methylene blue internalization and photodynamic action against clinical and ATCC
      Pseudomonas aeruginosa and Staphyloccocus aureus strains.
AB  - Bacterial infections have been a major challenge to health. Increasing resistance
      to antimicrobial agents, according to World Health Organization, could be the
      major cause of death until 2050. Photodynamic therapy emerges as an alternative
      in microbial inactivation, due to its selectivity and to decreasing or dismissing
      antibiotic use. This study aimed at evaluating, in vitro, the internalization of
      the Methylene Blue and its photodynamic activity against a clinical and ATCC
      strain of Pseudomonas aeruginosa and Staphyloccocus aureus. Thus, the strains
      were incubated with MB in concentrations of 100, 300 e 500 MUg/ml and then
      irradiated with a LED (+/-660 nm) at fluence of 10 and 25 J/cm2. The MB
      internalization was evaluated using a confocal microscope (Zeiss LSM 700), to
      capture the MB and the DAPI (for DNA staining). It was possible to observe that
      the MB was internalized by the bacterial cells, in all concentrations tested. The
      CFU/ml count demonstrated significant reduction (p <= 0,01) at the average 5.0
      logs comparing with control group for the two species in all the tested
      concentrations. In conclusion, the strains tested were capable of internalizing
      the MB. PDT with MB was able to decrease the growth of the tested strains in
      vitro, being a promising alternative to the future treatment of infections caused
      by these species.

PMID- 29454902
TI  - Syndecan-1 inhibits early stages of liver fibrogenesis by interfering with
      TGFbeta1 action and upregulating MMP14.
AB  - Increased expression of syndecan-1 is a characteristic feature of human liver
      cirrhosis. However, no data are available on the significance of this alteration.
      To address this question we designed a transgenic mouse strain that driven by
      albumin promoter, expresses human syndecan-1 in the hepatocytes. Liver cirrhosis
      was induced by thioacetamide in wild type and hSDC1+/+ mice of the identical
      strain. The process of fibrogenesis, changes in signal transduction and
      proteoglycan expression were followed. In an in vitro experiment, the effect of
      syndecan-1 overexpression on the action of TGFbeta1 was determined. Human
      syndecan-1 and TGFbeta1 levels were measured by ELISA in the circulation. Without
      challenge, no morphological differences were observed between wild type and
      transgenic mice livers, although significant upregulation of phospho-Akt and FAK
      was observed in the latter. Fibrogenesis in the transgenic livers, characterized
      by picrosirius staining, collagen type I, and SMA levels, lagged behind that of
      control in the first and second months. Changes in signal transduction involved
      in the process of fibrogenesis, as SMAD, MAPK, Akt and GSK, pointed to the
      decreased effect of TGFbeta1, and this was corroborated by the decreased mRNA
      expression of TIEG and the growth factor itself. In vitro experiments exposing
      the LX2 hepatic stellate cell line to conditioned media of wild type and syndecan
      1 transfected Hep3B cell lines proved that medium with high syndecan-1 content
      inhibits TGFbeta1-induced upregulation of SMA, TIEG, collagen type I and
      thrombospondin-1 expression. Detection of liver proteoglycans and heparan sulfate
      level revealed that their amounts are much higher in control transgenic liver,
      than that in the wild type. However, it decreases dramatically as a result of
      shedding after hepatic injury. Shedding is likely promoted by the upregulation of
      MMP14. As syndecan-1 can bind thrombospondin-1, and as our result demonstrated
      that the same is true for TGFbeta1, shed syndecan-1 can remove the growth factor
      and its activator together into the systemic circulation.Taking together, our
      results indicate that the effect of syndecan-1 is accomplished on two levels: a,
      the shedded syndecan can bind, inhibit and remove TGFbeta1; b, interferes with
      the activation of TGFbeta1 by downregulation and binding thrombospondin-1, the
      activator of the growth factor. However, by the end of the fourth month the
      protective effect was lost, which is explained by the considerable decrease of
      syndecan-1 and the almost complete loss of heparan sulfate from the surface of
      hepatocytes.

PMID- 29454903
TI  - Estrogen receptor-alpha isoforms are the main estrogen receptors expressed in non
      small cell lung carcinoma.
AB  - The expression profile of estrogen receptors (ER) in Non-Small Cell Lung
      Carcinoma (NSCLC) remains contradictory. Here we investigated protein and
      transcriptome expression of ERalpha wild type and variants. Tissue Micro-Arrays
      of 200 cases of NSCLC (paired tumor/non-tumor) were assayed by
      immunohistochemistry using a panel of ERalpha antibodies targeting different
      epitopes (HC20, 6F11, 1D5, ERalpha36 and ERalpha17p). ERbeta epitopes were also
      examined for comparison. In parallel we conducted a probe-set mapping (Affymetrix
      HGU133 plus 2 chip) meta-analysis of 12 NSCLC tumor public transcriptomic studies
      (1418 cases) and 39 NSCLC cell lines. Finally, we have investigated early
      transcriptional effects of 17beta-estradiol, 17beta-estradiol-BSA, tamoxifen and
      their combination in two NSCLC cell lines (A549, H520). ERalpha transcript and
      protein detection in NSCLC specimens and cell lines suggests that extranuclear
      ERalpha variants, like ERalpha36, prevail, while wild-type ERalpha66 is minimally
      expressed. In non-tumor lung, the wild-type ERalpha66 is quasi-absent. The
      combined evaluation of ERalpha isoform staining intensity and subcellular
      localization with sex, can discriminate NSCLC subtypes and normal lung. Overall
      ERalpha transcription decreases in NSCLC. ERalpha expression is sex-related in
      non-tumor tissue, but in NSCLC it is exclusively correlating with tumor
      histologic subtype. ERalpha isoform protein expression is higher than ERbeta.
      ERalpha isoforms are functional and display specific early transcriptional
      effects following steroid treatment. In conclusion, our data show a wide
      extranuclear ERalpha-variant expression in normal lung and NSCLC that is not
      reported by routine pathology ER evaluation criteria, limited in the nuclear wild
      type receptor.

PMID- 29454904
TI  - Protective effect of sodium stearate on the moisture-induced deterioration of
      hygroscopic spray-dried powders.
AB  - Amorphous powders are thermodynamically unstable, significantly impacting the
      processing, storage and performance of a product. Therefore, stabilization of the
      amorphous contents is in demand. In this study, disodium cromoglycate (DSCG)
      powder was chosen as a model drug because it is amorphous and highly hygroscopic
      after spray drying. Sodium stearate (NaSt) was co-spray dried with DSCG at
      various concentrations (10, 50 and 90% w/w) to investigate its effect against
      moisture-induced deterioration on the in vitro aerosolization performance of
      DSCG. Particle size distribution and morphology were measured by laser
      diffraction and scanning electron microscopy (SEM). Physicochemical properties of
      the powders were analysed by X-ray powder diffraction (XRPD) and dynamic vapour
      sorption (DVS). Particle surface chemistry was analysed by the time-of-flight
      secondary ion mass spectrometry (ToF-SIMS). In vitro dissolution behaviours of
      the spray-dried (SD) powders were tested by the Franz cell apparatus. In vitro
      aerosolization performance of SD formulations stored at different relative
      humidity (RH) was evaluated by a multi-stage liquid impinger (MSLI), using an
      Osmohaler(r) at 100 L/min. Results showed that adding NaSt in the formulation not
      only increased the aerosolization performance of DSCG significantly, but also
      effectively reduced the deleterious impact of moisture. No significant difference
      was found in the fine particle fraction (FPF) of formulations containing NaSt
      before and after storage at both 60% and 75% RH for one week. However, after one
      month storage at 75% RH, SD formulation containing 10% NaSt showed a reduction in
      FPF, while formulations containing 50% or 90% NaSt showed no change. The
      underlying mechanism was that NaSt increased the crystallinity of the powders and
      its presence on the particle surface reduced particle aggregations and
      cohesiveness. However, NaSt at high concentration could reduce dissolution rate,
      which needs to be taken into consideration.

PMID- 29454905
TI  - Relationships between surface coverage ratio and powder mechanics of binary
      adhesive mixtures for dry powder inhalers.
AB  - The aim of this paper was to study relationships between the content of fine
      particles and the powder mechanics of binary adhesive mixtures and link these
      relationships to the blend state. Mixtures with increasing amounts of fine
      particles (increasing surface coverage ratios (SCR)) were prepared using
      Lactopress SD as carrier and micro particles of lactose as fines (2.7 um).
      Indicators of unsettled bulk density, compressibility and flowability were
      derived and the blend state was visually examined by imaging. The powder
      properties studied showed relationships to the SCR characterised by stages. At
      low SCR, the fine particles predominantly gathered in cavities of the carriers,
      giving increased bulk density and unchanged or improved flow. Thereafter,
      increased SCR gave a deposition of particles at the enveloped carrier surface
      with a gradually more irregular adhesion layer leading to a reduced bulk density
      and a step-wise reduced flowability. The mechanics of the mixtures at a certain
      stage were dependent on the structure and the dynamics of the adhesion layer and
      transitions between the stages were controlled by the evolution of the adhesion
      layer. It is advisable to use techniques based on different types of flow in
      order to comprehensively study the mechanics of adhesive mixtures.

PMID- 29454906
TI  - Risk factors for Pseudomonas aeruginosa infections in Asia-Pacific and
      consequences of inappropriate initial antimicrobial therapy: A systematic
      literature review and meta-analysis.
AB  - OBJECTIVES: Treating infections of Gram-negative pathogens, in particular
      Pseudomonas aeruginosa, is a challenge for clinicians in the Asia-Pacific region
      owing to inherent and acquired antimicrobial resistance. This systematic review
      and meta-analysis provides updated information on risk factors for P. aeruginosa
      infection in Asia-Pacific as well as the consequences (e.g. mortality, costs) of
      initial inappropriate antimicrobial therapy (IIAT). METHODS: Embase and MEDLINE
      databases were searched for Asia-Pacific studies reporting the consequences of
      IIAT versus initial appropriate antimicrobial therapy (IAAT) in Gram-negative
      bacterial infections as well as risk factors for serious P. aeruginosa infection.
      A meta-analysis of unadjusted mortality was performed using a random-effects
      model. RESULTS: A total of 22 studies reporting mortality and 13 reporting risk
      factors were identified. The meta-analysis demonstrated that mortality was
      significantly lower in patients receiving IAAT versus IIAT, with a 67% reduction
      observed for 28- or 30-day all-cause mortality (odds ratio=0.33, 95% confidence
      interval 0.20-0.55; P<0.001). Risk factors for serious P. aeruginosa infection
      include previous exposure to antimicrobials, mechanical ventilation and previous
      hospitalisation. CONCLUSION: High rates of antimicrobial resistance in Asia
      Pacific as well as the increased mortality associated with IIAT and the presence
      of risk factors for serious infection highlight the importance of access to newer
      and appropriate antimicrobials.

PMID- 29454907
TI  - Sediment bacteria in an urban stream: Spatiotemporal patterns in community
      composition.
AB  - Sediment bacterial communities play a critical role in biogeochemical cycling in
      lotic ecosystems. Despite their ecological significance, the effects of urban
      discharge on spatiotemporal distribution of bacterial communities are
      understudied. In this study, we examined the effect of urban discharge on the
      spatiotemporal distribution of stream sediment bacteria in a northeast Ohio
      stream. Water and sediment samples were collected after large storm events
      (discharge > 100 m) from sites along a highly impacted stream (Tinkers Creek,
      Cuyahoga River watershed, Ohio, USA) and two reference streams. Although alpha
      (alpha) diversity was relatively constant spatially, multivariate analysis of
      bacterial community 16S rDNA profiles revealed significant spatial and temporal
      effects on beta (beta) diversity and community composition and identified a
      number of significant correlative abiotic parameters. Clustering of upstream and
      reference sites from downstream sites of Tinkers Creek combined with the dominant
      families observed in specific locales suggests that environmentally-induced
      species sorting had a strong impact on the composition of sediment bacterial
      communities. Distinct groupings of bacterial families that are often associated
      with nutrient pollution (i.e., Comamonadaceae, Rhodobacteraceae, and
      Pirellulaceae) and other contaminants (i.e., Sphingomonadaceae and
      Phyllobacteriaceae) were more prominent at sites experiencing higher degrees of
      discharge associated with urbanization. Additionally, there were marked seasonal
      changes in community composition, with individual taxa exhibiting different
      seasonal abundance patterns. However, spatiotemporal variation in stream
      conditions did not affect bacterial community functional profiles. Together,
      these results suggest that local environmental drivers and niche filtering from
      discharge events associated with urbanization shape the bacterial community
      structure. However, dispersal limitations and interactions among other species
      likely play a role as well.

PMID- 29454908
TI  - The ranking of scientists.

PMID- 29454909
TI  - Letters to the Editor.

PMID- 29454910
TI  - The ranking of scientists.

PMID- 29454911
TI  - The ranking of scientists.

PMID- 29454912
TI  - Anticancer effect of petroleum ether extract from Bidens pilosa L and its
      constituent's analysis by GC-MS.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bidens pilosa L, belonging to the family of
      Acanthaceae, has been used as an anticancer medicine in folk in China. In our
      preliminary experiments, the petroleum ether extract from B. pilosa showed good
      cytotoxic activity to human lung cancer A549 cell. However, to date, it's lack of
      the further study on antitumor effect, mechanism and active substances
      composition of the petroleum ether extract of B. pilosa. AIM OF THE STUDY: The
      study aimed to evaluate the anti-lung cancer efficacy of the petroleum ether
      extract from B. pilosa (PEEBP) in vitro and in vivo, explore the possible
      anticancer mechanisms, and further disclose the chemical composition of the
      extract. MATERIALS AND METHODS: B. pilosa was extracted with 75% ethanol (v/v),
      followed by extracted with petroleum ether to obtain the objective fraction.
      Antiproliferation effect of the petroleum ether extract in HepG2, A549, CNE and
      B16 cells was evaluated by MTT assay. The in vivo anticancer effect was examined
      by A549 cells nude mice xenograft tumor model. The possible effect mechanism was
      studied by western blot assay. The chemical constituents of the extract was
      analyzed by GC-MS. RESULTS: The petroleum ether extract showed favorable
      antiproliferation activity against the four human cancer cell lines, especially
      for A549 cells with an IC50 of 49.11 +/- 2.72 MUg/mL. The extract inhibited the
      growth of A549 cell in mice with the inhibitory rates of 24.76%, 35.85% and
      53.07% for 90, 180 and 360 mg/kg oral dosages, respectively. The B. pilosa
      extract could significantly down-regulate the expression of apoptosis-related
      protein Bcl-2 and up-regulate the protein expression of Bax and Caspase-3. 138
      compounds were identified by GC-MS in the extract and the main chemical
      components were triterpenes, including 4,22-cholestadien-3-one (4.82%),
      stigmasterol (4.56%), friedelan-3-one (3.28%), etc. CONCLUSION: The PEEBP is
      abundant of triterpenes and has significant anti-tumor activities against human
      A549 cells in vitro and in vivo, indicating it a potential anticancer agent.

PMID- 29454913
TI  - Restoring Th17/Treg balance via modulation of STAT3 and STAT5 activation
      contributes to the amelioration of chronic obstructive pulmonary disease by Bufei
      Yishen formula.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Bufei Yishen formula (BYF), a Traditional Chinese
      Medicine (TCM), has been extensively applied in clinical treatment of chronic
      obstructive pulmonary disease (COPD) and provides an effective treatment strategy
      for the syndrome of lung-kidney qi deficiency in COPD patients. Here, we
      investigated its anti-COPD mechanism in COPD rats in relation to the balance
      between T helper (Th) 17 cells and regulatory T (Treg) cells. METHODS: Rat model
      of cigarette smoke- and bacterial infection-induced COPD was established, and
      orally treated with BYF for 12 consecutive weeks. Then, the rats were sacrificed,
      their lung tissues were removed for histological analysis, and spleens and
      mesenteric lymph nodes (MLNs) were collected to evaluate the Th17 and Treg cells.
      RESULTS: Oral treatment of BYF markedly suppressed the disease progression and
      alleviated the pathological changes of COPD. It also decreased the
      bronchoalveolar lavage fluid (BALF) levels of pro-inflammatory cytokines,
      including IL-1beta, IL-6, TNF-alpha and Th17-related IL-17A, and induced a
      significant increase in Treg-related IL-10. Furthermore, BYF treatment obviously
      decreased the proportion of CD4+RORgammat+ T (Th17) cell and increased the
      proportion of CD4+CD25+Foxp3+ T (Treg) cell, leading to restore the Th17/Treg
      balance. BYF treated groups also decreased RORgammat and increased Foxp3
      expression in the spleens and MLNs. BYF further inhibited the phosphorylation of
      signal transducer and activator of transcription-3 (STAT3) and boosted the
      phosphorylation of STAT5, that were critical transcription factors for TH17 and
      Treg differentiation. CONCLUSION: these results demonstrated that BYF exerted its
      anti-COPD efficacy by restoring Th17/Treg balance via reciprocally modulating the
      activities of STAT3 and STAT5 in COPD rats, which may help to elucidate the
      underlying immunomodulatory mode of BYF on COPD treatment.

PMID- 29454914
TI  - Substituting one Paris for another? In vitro cytotoxic and in vivo antitumor
      activities of Paris forrestii, a substitute of Paris polyphylla var. yunnanensis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chong-lou (Paris polyphylla var. yunnanensis or
      P. polyphylla var. chinensis) is traditionally used as an anticancer medicine in
      China. It is also the material basis of some Chinese patent anticancer medicines,
      such as Gan-Fu-Le capsules, Bo-Er-Ning capsules, Lou-Lian capsules, Ruan-Jian
      oral liquid, and Qi-Zhen capsules. P. forrestii, a substitute for Chong-lou, is
      planted at a large scale in the Yunnan Province of China. AIM OF THE STUDY: To
      clarify the active chemical constituents of P. forrestii and evaluate the in
      vitro and in vivo anticancer activities of the total saponins from P. forrestii.
      MATERIALS AND METHODS: The total saponins of P. forrestii were extracted and
      separated to yield pure compounds by chromatographic techniques, and the
      structures of the isolates were elucidated by spectroscopic methods. The
      cytotoxicity of the crude extracts, total saponins, and chemical constituents
      were evaluated using an MTS assay. In vivo antitumor activities of the total
      saponins from P. forrestii were measured using H22 tumor-bearing mice by
      intraperitoneal (ip) administration. RESULTS: Eight compounds, including
      polyphyllin D (1), formosanin C (2), dioscin (3), diosgenin-3-O-alpha-l
      rhamnopyranosyl-(1->2)-beta-d-glucopyranoside (4), paris saponin H (5),
      pennogenin-3-O-alpha-l-rhamnopyranosyl-(1->2)-[alpha-l-rhamnopyranosyl-(1->4)]
      beta-d-glucopyranoside (6), pariposide A (7), and crustecdysone (8), were
      isolated from the total saponins of P. forrestii. The total saponins and
      compounds 1-6 showed significant inhibitory activity against the growth of the HL
      60, SMMC-7721, A-549, MCF-7, and SW480 cell lines. The total saponins from P.
      forrestii had a tumor-inhibitory effect in H22 tumor-bearing mice upon ip (2.25
      mg/kg dose) administration, with an inhibition rate of 42.6% compared with
      cisplatin (ip, 2 mg/kg dose, 53.9% inhibition rate). CONCLUSION: The results
      support that P. forrestii could be a substitute for P. polyphylla var.
      yunnanensis as an anticancer medicine.

PMID- 29454915
TI  - Synthesis of N-(1-(6-acetamido-5-phenylpyrimidin-4-yl) piperidin-3-yl) amide
      derivatives as potential inhibitors for mitotic kinesin spindle protein.
AB  - Kinesin Spindle Protein (KSP) or Eg5 is an essential kinesin that is involved in
      spindle separation process during mitosis and also unregulated in certain cancer
      cells. Inhibitors of this enzyme have proved to be effective to block spindle
      separation followed by mitotic arrest and apoptosis of the cancer cells. Since
      this enzyme has two allosteric inhibitor binding sites, it's an excellent target
      for developing drugs for cancer chemotherapy. Many pyrimidine derivatives have
      been proved to be active against cancer and other enzymes. In this report, we
      have synthesized a set ten novel N-(1-(6-acetamido-5-phenylpyrimidin-4
      yl)piperidin-3-yl)amide derivatives and have evaluated their activity against the
      KSP. The SAR of these active compounds was further analyzed using in silico
      molecular docking studies using GOLD and AutoDock softwares. All these compounds
      form hydrophobic interaction, aromatic pi-pi stacking and hydrogen bond
      efficiently with the Eg5.

PMID- 29454916
TI  - Mitochondria-targeting indolizino[3,2-c]quinolines as novel class of
      photosensitizers for photodynamic anticancer activity.
AB  - To achieve efficient photodynamic activity, substantial effort has been dedicated
      to precise control of the intracellular localization of current photosensitizers
      (PSs). Given the extremely small radius of action of singlet oxygen, the direct
      targeting of PSs to the mitochondria is expected to greatly enhance the
      photodynamic therapy (PDT) activity. Here, we report mitochondria-targeting 6
      (furan-2-yl)- and 6-(thiophen-2-yl) indolizino[3,2-c]quinolines (IQs) as novel
      PSs. IQ derivatives containing 5-membered heterocyclic aromatic rings were
      synthesized, and their photophysical properties as PSs were characterized. The
      anticancer potentials of 2a-2f were investigated using various cancer cell lines,
      and they exhibited dose-dependent and light exposure time-dependent cytotoxicity.
      Among the synthesized compounds, 2b, which contains a furan ring, showed dual
      functions as an imaging probe as well as a PS. Real-time confocal fluorescence
      images revealed the mitochondrial localization of 2b as a primary site of
      photodamage in live cells. Targeted reactive oxygen species (ROS)-generation
      capabilities and the photoinduced DNA cleavage of IQs led to mitochondrial
      dysfunction and photoinduced apoptosis via the intrinsic pathway. 3D RI tomograms
      of individual live HeLa cells treated with 2b showed that the progress of
      photoinduced apoptosis was affected by the PS concentration and light irradiation
      time. The studied IQs (2b, 2d, and 2e) are expected to serve as a new class of
      heavy-atom-free PSs with low molecular weights less than 350.

PMID- 29454917
TI  - Marine derived xyloketal derivatives exhibit anti-stress and anti-ageing effects
      through HSF pathway in Caenorhabditis elegans.
AB  - Ageing is a complex but universal phenomenon that progressively challenges the
      homeostasis network and finally leads to the dysfunction of organisms and even
      death. Previous studies demonstrated that xyloketal B and its derivatives, a
      series of marine novel ketone compounds, possessed unique antioxidative effects
      on endothelial and neuronal oxidative injuries. In this study, we examined the
      effects of xyloketal derivatives on extending lifespan and healthspan of
      Caenorhabditis elegans. The results showed that most selected xyloketals could
      protect Caenorhabditis elegans against heat stress and extend the lifespan of
      worms. Compound 15, a benzo-1, 3-oxazine xyloketal derivative, possessed most
      potent effect in anti-heat stress assay and significantly attenuated ageing
      related decrease of pumping and bending of the worms in healthspan assay. In
      addition, the beneficial effect of 15 was abolished in PS3551 worms, a strain
      that possesses non-functional heat shock transcription factor-1 (HSF-1).
      Furthermore, 15 increased the expression of heat shock protein 70 (HSP70), a
      downstream molecular chaperone of HSF-1. These results indicated that HSF-1 might
      contribute to the protective effect of this compound in Caenorhabditis elegans
      ageing. Molecular docking studies suggested that these xyloketal derivatives were
      bound to the DNA binding domain of HSF-1, promoted the conformation of HSF-1,
      thus strengthened the interaction between the HSF-1 and related DNA. ALA-67, ASN
      74 and LYS-80 of binding region might be the key amino residues during the
      interaction. Finally, compound 15 could reduce the paralysis of the CL4176 worms,
      a transgenic strain expressing human Abeta3-42 under a temperature-inducible
      system. Collectively, these data indicate that xyloketals have potential
      implications for further evaluation in anti-ageing studies.

PMID- 29454918
TI  - Design, synthesis, and biological evaluation of novel amide and hydrazide based
      thioether analogs targeting Histone deacteylase (HDAC) enzymes.
AB  - Development of HDAC inhibitors have become an ultimate need targeting different
      types of cancer. In silico virtual screening was applied to screen novel
      scaffolds via scaffold hopping strategy to develop different acrylamide and
      aryl/heteroaryl hydrazide based analogs merged with thioether moiety. The
      acrylamide based analogs showed significant hydrophobic interaction within
      binding pocket in addition to co-ordination with Zn+2 via carbonyl group, however
      the aryl/heteroaryl hydrazide based analogs showed binding towards Zn+2 via thiol
      moiety. Two classes (acrylamide and aryl/heteroaryl hydrazide based analogs) were
      synthesized to be screened along with 60 cancer cell lines panel to reveal that
      both of AHM-4 and AHM-5 showed significant inhibitory growth against HL-60
      (Leukemia cell lines) at GI50 2.87 MUM and 3.20 MUM, respectively and MDA-MB-435
      (Melanoma cell lines) cell lines at GI50 of 0.37 MUM and 0.42 MUM, respectively.
      AHM-4 and AHM-5 showed general inhibitory profile against class I HDAC enzymes
      with differential inhibitory activity towards HDAC 2 at IC50 32 nM and 20 nM,
      respectively via ELISA enzymatic assay, in addition to inhibiting activity for
      the expression of class I HDAC enzymes via real time PCR with differential
      selective inhibition against HDAC 2 up to 10 folds, compared to control. AHM4 and
      AHM5 showed cell cycle arrest action at G2/M phase along with induction of
      apoptosis via assessment of apoptotic parameters such as Caspase 3, 9, and gamma-
      H2AX. The synthesized analogs offer novel scaffold to be further optimized for
      development of HDAC inhibitors.

PMID- 29454919
TI  - Structure-activity relationships of talaumidin derivatives: Their neurite
      outgrowth promotion in vitro and optic nerve regeneration in vivo.
AB  - (-)-Talaumidin (1), a 2,5-biaryl-3,4-dimethyltetrahydrofuran lignan, shows potent
      neurotrophic activities such as neurite-outgrowth promotion and neuroprotection.
      Previously, we found that (-)-(1S,2R,3S,4R)-stereoisomer 2 exhibited more
      significant activity than did the natural product talaumidin (1). However, the
      preparation of optically active (-)-2 requires a complicated synthetic route. To
      explore new neurotrophic compounds that can be obtained on a large scale, we
      established a short step synthetic route for talaumidin derivatives and
      synthesized fourteen analogues based on the structure of (-)-2. First, we
      synthesized a racemic compound of (-)-2 (2a) and assessed its neurotrophic
      activity. We found that the neurotrophic property of racemic 2a is similar in
      activity to that of (-)-2. Using the same synthetic methodology, several
      talaumidin derivatives were synthesized to optimize the oxy-functionality on
      aromatic rings. As a result, bis(methylenedioxybenzene) derivative 2b possessed
      the highest neurotrophic activity. Furthermore, examination of the structure
      activity relationships of 2b revealed that the 2,5-diphenyl-tetrahydrofuran
      structure was an essential structure and that two methyl groups on THF ring could
      enhance neurotrophic activity. In addition, compounds 2a and 2b were found to
      induce mouse optic nerve regeneration in vivo.

PMID- 29454920
TI  - Design, synthesis and identification of silicon-containing HCV NS5A inhibitors
      with pan-genotype activity.
AB  - Modification of a HCV NS5A inhibitor, ombitasvir, led to the identification of
      10d with improved pan-genotype NS5A inhibition and better pharmacokinetic
      properties. The key structural changes to ombitasvir include bioisosteric
      replacement of carbon with silicon atom. Compared with ombitasvir, the activity
      of anti-HCV genotypes (GT 1 to 6) of 10d is increased to some extent, especially
      the inhibitory activity against genotype 3a and 6a is increased by more than
      seven times, and the dog's in vivo pharmacokinetics properties were also superior
      to ombitasvir. Further drug evaluation showed that 10d was similar to ombitasvir
      on plasma protein binding and liver distribution profiles, with no cytotoxicity
      and no inhibitory effect on both CYP 450 and hERG ligand binding. However,
      permeability assay results indicated that 10d was not the substrate of P-gp or
      BCRP transporter, which is different from that of ombitasvir. The results of a 14
      day repeat-dose toxicity study identified no toxicity with 10d. Our findings in
      preclinical tests suggest that the silicon-containing compound 10d could be
      worthy of continued study as a potential drug candidate.

PMID- 29454921
TI  - Sequential pretreatment for cell disintegration of municipal sludge in a neutral
      Bio-electro-Fenton system.
AB  - Sludge cell disruption was generally considered as the rate-limiting step for the
      anaerobic digestion of waste activated sludge (WAS). Advanced oxidation processes
      and bio-electro-chemical systems were recently reported to enhance the hydrolysis
      of WAS and sludge cell disruption, while the cell-breaking processes of these
      systems remain unclear yet. In this study, an innovative Bio-electro-Fenton
      system was developed to pretreat the WAS sequentially with cathode Fenton process
      and anode anaerobic digestion. Significant cell disruption and dissolution
      intracellular organics were founded after the treatment. X-ray photoelectron
      spectroscopy (XPS) analysis and fourier transform infrared spectroscopy (FT-IR)
      spectra indicated that Gram-negative bacteria were more sensitive to free
      radicals yielded in cathode to induce a chain reaction that destroyed the lipid
      contained outer membrane, while Gram-positive bacteria with thick peptidoglycan
      layer were liable to be biologically decomposed in the anode. Compared with the
      oxidation of organic matters in the cathode Fenton, the secretion of enzyme
      increased in the anode which was beneficial to break down the complex matters
      (peptidoglycans) into simples that were available for anode oxidation by
      exoelectrogens. The results also showed a possible prospect for the application
      of this sequential pretreatment in bio-electro-Fenton systems to disrupt sludge
      cells and enhance the anaerobic digestion.

PMID- 29454922
TI  - Nutrient recovery from wastewater through pilot scale electrodialysis.
AB  - Nutrient recovery performance utilising an electrodialysis (ED) process was
      quantified in a 30-cell pair pilot reactor with a 7.2 m2 effective membrane area,
      utilising domestic anaerobic digester supernatant, which had been passed through
      a centrifuge as a feed source (centrate). A concentrated product (NH4-N 7100 +/-
      300 mg/L and K 2490 +/- 40 mg/L) could be achieved by concentrating nutrient ions
      from the centrate wastewater dilute feed stream to the product stream using the
      ED process. The average total current efficiency for all major cations over the
      experimental period was 76 +/- 2% (NH4-N transport 40%, K transport 14%). The
      electrode power consumption was 4.9 +/- 1.5 kWh/kgN, averaged across the three
      replicate trials. This value is lower than competing technologies for NH4-N
      removal and production, and far lower than previous ED lab trials, demonstrating
      the importance of pilot testing. No significant variation in starting flux
      densities and cell resistance voltage for subsequent replicate treatments
      indicated effective cleaning procedures and operational sustainability at
      treatment durations of several days. This study demonstrates that ED is an
      economically promising technology for the recovery of nutrients from wastewater.

PMID- 29454923
TI  - Seasonal differences in the content of phenols and pigments in thalli of
      freshwater Cladophora glomerata and its habitat.
AB  - Polyphenols are chemicals that primarily inhibit the growth of various
      autotrophic organisms. The presence of these metabolites greatly boosts the
      ecological dominance of eg. Cladophora, which creates large surface mats. The
      main goal of our work was to quantify the phenol and polyphenols (allelopathic
      substances) secreted by the macroalgae as a result of exposure to biotic stress
      caused by competition. The research was carried out on the Cladophora glomerata
      biomass collected from two freshwater ecosystems located in Wielkopolska Region
      (Poland, Fig. 1): Oporzynskie Lake (N52 degrees  55', E 17 degrees  9') and
      Nielba River (N5248', E 17 degrees  12'). Seasonal variability (May-October 2015)
      in the properties of C. glomerata mats in the river and lake ecosystem was also
      analyzed in relation to the physicochemical parameters of water. In addition, the
      content of pigments in the analyzed biomass was determined during the appearance
      of algae mats in water reservoirs. Biomass extraction was performed to determine
      the phenolic and carotenoid contents (chlorophyll and carotenoids) by using two
      extraction methods: microwave-assisted extraction (MAE) and supercritical fluid
      extraction (SFE). After isolation of the phenols from the thalli (mats) and the
      habitat, they were analyzed using the Folin-Ciocalteu method with some
      modifications, while the pigment content (chlorophyll and carotenoids) was
      evaluated by the spectrophotometric method Liechtenthaler (1987) with some
      variations. Analysis of the content of these components in algae extracts
      indicates that the tendency of changes in their contents was similar or the same.
      Growth and decrease of phenolic content (Cladophora T MAE and Cladophora T SFE)
      and pigments (MAE chlorophyll, SFE and MAE carotenoids) at the same time were
      independent of the insulation method used. The mats formed by C. glomerata on the
      surface of Lake Oporzynskie were more stable and larger surface area than those
      on the Nielba River, which could explain differences in polyphenol concentrations
      in these two aquatic ecosystems. The results suggest a reduction in the secretion
      of phenolic compounds with an aging population of algae.

PMID- 29454924
TI  - Transformation of Methylparaben by aqueous permanganate in the presence of
      iodide: Kinetics, modeling, and formation of iodinated aromatic products.
AB  - This work investigated impacts of iodide (I-) on the transformation of the widely
      used phenolic preservative methylparaben (MeP) as well as 11 other phenolic
      compounds by potassium permanganate (KMnO4). It was found that KMnO4 showed a low
      reactivity towards MeP in the absence of I- with apparent second-order rate
      constants (kapp) ranging from 0.065 +/- 0.0071 to 1.0 +/- 0.1 M-1s-1 over the pH
      range of 5-9. The presence of I- remarkably enhanced the transformation rates of
      MeP by KMnO4 via the contribution of hypoiodous acid (HOI) in situ formed, which
      displayed several orders of magnitude higher reactivity towards MeP than KMnO4.
      This enhancing effect of I- was greatly influenced by solution conditions (e.g.,
      I- or KMnO4 concentration or pH), which could be well simulated by a kinetic
      model involving competition reactions (i.e., KMnO4 with I-, KMnO4 with MeP, HOI
      with KMnO4, and HOI with MeP). Similar enhancing effect of I- on the
      transformation kinetics of 5 other selected phenols (i.e., p-hydroxybenzoic acid,
      phenol, and bromophenols) at pH 7 was also observed, but not in the cases of
      bisphenol A, triclosan, 4-n-nonylphenol, and cresols. This discrepancy could be
      well explained by the relative reactivity of KMnO4 towards phenols vs I-. Liquid
      chromatography-tandem mass spectrometry analysis showed that iodinated aromatic
      products and/or iodinated quinone-like product were generated in the cases where
      I- enhancing effect was observed. Evolution of iodinated aromatic products
      generated from MeP (10 MUM) treated by KMnO4 (50-150 MUM) in the presence of I-
      (5-15 MUM) suggested that higher I- or moderate KMnO4 concentration or neutral pH
      promoted their formation. A similar enhancing effect of I- (1 MUM) on the
      transformation of MeP (1 MUM) by KMnO4 (12.6 MUM) and formation of iodinated
      aromatic products were also observed in natural water. This work demonstrates an
      important role of I- in the transformation kinetics and product formation of
      phenolic compounds by KMnO4, which has great implications for future applications
      of KMnO4 in treatment of I--containing water.

PMID- 29454925
TI  - A mechanistic study of stable dispersion of titanium oxide nanoparticles by humic
      acid.
AB  - Stable dispersion of nanoparticles with environmentally-friendly materials is
      important for their various applications including environmental remediation. In
      this study, we systematically examined the mechanisms of stable dispersion of two
      types of TiO2 nanoparticles (TNPs) with anatase and rutile crystalline structures
      by naturally occurring dissolved organic matter (humic acid) at different pHs,
      including at, below and above the Point of Zero Charge (PZC). The results showed
      that stable dispersion of TNPs by humic acid (HA) at all pHs tested can only be
      achieved with the assistance of ultra-sonication. The dispersion of TNPs by HA
      differed at the three pHs tested. Generally, HA greatly decreased the
      hydrodynamic diameters of TNPs at a very low concentration. The dispersion of
      TNPs became relatively stable when the HA concentration exceeded 5 mg/L,
      indicating that this HA concentration is required for stable dispersion of TNPs.
      The mechanisms involved in dispersion of TNPs by HA included electrostatic
      repulsion, steric hindrance and hydrophobic interaction. Electrostatic repulsion
      was identified to be the dominant mechanism. The dispersion of TNPs was enhanced
      when HA was added before ultra-sonication to avoid the partly irreversible re
      aggregation of TNPs after sonication. The crystalline phases and concentrations
      of TNPs were also found to influence their stable dispersion. The findings from
      this work enhance understanding of the combined effects of HA, pH, ultra
      sonication and crystalline structures of TNPs on their stable dispersion. The
      mechanisms identified can improve applications of TNPs in environmental water
      pollution control.

PMID- 29454926
TI  - Chinese patent medicine Xin-Ke-Shu inhibits Ca2+ overload and dysfunction of
      fatty acid beta-oxidation in rats with myocardial infarction induced by LAD
      ligation.
AB  - Myocardial infarction (MI) occurs during a sustained insufficient blood supply to
      the heart, eventually leading to myocardial necrosis. Xin-Ke-Shu tablet (XKS) is
      a prescription herbal compound and a patented medicine extensively used in the
      clinical treatment of coronary heart disease (CHD). To understand the molecular
      mechanism of the XKS action against MI in detail, it is necessary to investigate
      the altered metabolome and related pathways coincident with clinical features. In
      this study, tissue-targeted metabonomics based on ultra-high-performance liquid
      chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q
      TOF/MS) were developed to explore the metabolic changes associated with XKS
      treatment in the heart tissue of rats with MI induced by a left anterior
      descending coronary artery ligation (LAD). The metabolic disorder induced by LAD
      was alleviated after low-dose XKS (LD) and intermediate-dose XKS (MD) treatment.
      XKS modulated six perturbed metabolic pathways. Among them, inhibition of Ca2+
      overload and dysfunction of fatty acid beta-oxidation-related metabolic pathways
      likely underlie the therapeutic effects of XKS against MI. In agreement with its
      observed effect on metabolite perturbation, XKS reversed the over-expression of
      the four key proteins, long-chain acyl-CoA synthetase 1 (ACSL1), carnitine
      palmitoyl transferase-1 (CPT1B), calcium/calmodulin-dependent kinase II (CaMKII),
      and phospholipase A2IIA (PLA2IIA). Both metabolite and protein changes suggested
      that XKS exerts its therapeutic effect on metabolic perturbations in LAD-induced
      MI mainly by inhibiting the Ca2+ overload and fatty acid beta-oxidation
      dysfunction.

PMID- 29454927
TI  - Syndemics among individuals enrolled in the PrEP Brasil Study.
AB  - BACKGROUND: Concurrent psychosocial problems may synergistically increase the
      risk of HIV infection (syndemics), representing a challenge for prevention. We
      aimed to evaluate the prevalence and associated factors of syndemics among men
      who have sex with men (MSM) and transgender women (TGW) enrolled in the Brazilian
      pre-exposure prophylaxis demonstration study (PrEP Brasil Study). METHODS:
      Secondary cross-sectional analysis of the PrEP Brasil Study was performed. Of 450
      HIV-seronegative MSM/TGW enrolled in the PrEP Brasil Study- conducted at Rio de
      Janeiro and Sao Paulo, Brazil- 421 participants with complete data were included
      in the present analysis. Syndemics was defined as occurrence of >=2 of the
      following conditions: polysubstance (>=2) use, binge drinking, positive
      depression screen, compulsive sexual behavior, and intimate partner violence
      (IPV). RESULTS: The prevalence of recent polysubstance use was 22.8%, binge
      drinking 51.1%, positive depression screening 5.2%, compulsive sexual behavior
      7.1%, and IPV 7.3%. Syndemics prevalence was 24.2%, and associated factors were
      younger age (adjusted Odds Ratio (aOR) 0.95, 95% Confidence Interval (95% CI)
      0.92-0.98 per year increase), TGW vs. MSM (aOR 3.09, 95% CI: 1.2-8.0), some
      college education or more vs. less than college (aOR 2.49, 95% CI: 1.31-4.75),
      and multiple male sexual partners in prior 3 months (aOR 1.69, 95% CI: 0.92
      3.14). CONCLUSION: Given the high prevalence of syndemics, particularly of
      polysubstance use and binge drinking, PrEP delivery offers an opportunity to
      diagnose and intervene in mental and social well-being.

PMID- 29454930
TI  - Expanding horizons of cryo-tomography to larger volumes.
AB  - The three dimensional ultrastructure of cells and tissues comes to light with
      tomography. There is an inherent tension between representing molecular detail at
      the highest possible resolution, on one hand, and visualizing spatial relations
      between large organelles or even neighboring cells in large volumes, on the
      other. Together with its advantages for pristine sample preservation, cryo
      tomography brings particular constraints. A major challenge has been the
      restriction to specimens thinner than the typical cell. New imaging modalities
      are now available to extend cryo-tomography to thicker specimens: cryo-scanning
      transmission electron tomography (CSTET), soft X-ray tomography (SXT), and serial
      surface imaging using the focused ion beam-scanning electron microscope (FIB
      SEM). Each one offers specific advantages so the optimal choice depends on
      priorities among resolution, composition, and volume.

PMID- 29454929
TI  - HuR-mediated SCN5A messenger RNA stability reduces arrhythmic risk in heart
      failure.
AB  - BACKGROUND: Downregulated sodium currents in heart failure (HF) have been linked
      to increased arrhythmic risk. Reduced expression of the messenger RNA (mRNA)
      stabilizing protein HuR (also known as ELAVL1) may be responsible for the
      downregulation of sodium channel gene SCN5A mRNA. OBJECTIVE: The purpose of this
      article was to investigate whether HuR regulates SCN5A mRNA expression and
      whether manipulation of HuR benefits arrhythmia control in HF. METHODS:
      Quantitative real-time reverse-transcriptase polymerase chain reaction was used
      to investigate the expression of SCN5A. Optical mapping of the intact heart was
      adopted to study the effects of HuR on the conduction velocity and action
      potential upstroke in mice with myocardial infarct and HF after injection of AAV9
      viral particles carrying HuR. RESULTS: HuR was associated with SCN5A mRNA in
      cardiomyocytes, and expression of HuR was downregulated in failing hearts. The
      association of HuR and SCN5A mRNA protected SCN5A mRNA from decay. Injection of
      AAV9 viral particles carrying HuR increased SCN5A expression in mouse heart
      tissues after MI. Optical mapping of the intact heart demonstrated that
      overexpression of HuR improved action potential upstroke and conduction velocity
      in the infarct border zone, which reduced the risk of reentrant arrhythmia after
      MI. CONCLUSION: Our data indicate that HuR is an important RNA-binding protein in
      maintaining SCN5A mRNA abundance in cardiomyocytes. Reduced expression of HuR may
      be at least partially responsible for the downregulation of SCN5A mRNA expression
      in ischemic HF. Overexpression of HuR may rescue decreased SCN5A expression and
      reduce arrhythmic risk in HF. Increasing mRNA stability to increase ion channel
      currents may correct a fundamental defect in HF and represent a new paradigm in
      antiarrhythmic therapy.

PMID- 29454928
TI  - Resting state functional connectivity of the amygdala and problem drinking in non
      dependent alcohol drinkers.
AB  - Alcohol misuse is associated with dysfunction of the amygdala-prefrontal cortical
      circuit. The amygdala and its cortical targets show decreased activity during a
      variety of task challenges in individuals engaged in problem drinking. On the
      other hand, it is less clear how amygdala resting state functional connectivity
      (rsFC) may be altered in association with alcohol misuse and whether such changes
      are restricted to prefrontal cortical structures. Further, the influences of
      comorbid substance use and depression and potential sex differences have not been
      assessed in earlier work. Here, with fMRI data from a Nathan Kline
      Institute/Rockland sample of 83 non-dependent alcohol drinkers (26 men), we
      addressed changes in whole brain rsFC of the amygdala in association with problem
      drinking as indexed by an alcohol involvement score. Imaging data were processed
      with Statistical Parametric Mapping following standard routines and all results
      were examined at voxel p < 0.001 uncorrected in combination with cluster p < 0.05
      corrected for false discovery rate. Alcohol misuse was correlated with decreased
      amygdala connectivity with the dorsal anterior cingulate cortex (dACC)
      irrespective of depression and other substance use. Changes in amygdala-dACC
      connectivity manifested in the latero-basal subdivision of the amygdala. Further,
      men as compared to women showed a significantly stronger relationship in
      decreased amygdala-dACC connectivity and problem drinking, although it should be
      noted that men also showed a trend toward higher alcohol involvement score than
      women. The findings add to a growing literature documenting disrupted amygdala
      prefrontal cortical functions in relation to alcohol misuse.

PMID- 29454931
TI  - The soil microbiome-from metagenomics to metaphenomics.
AB  - Soil microorganisms carry out important processes, including support of plant
      growth and cycling of carbon and other nutrients. However, the majority of soil
      microbes have not yet been isolated and their functions are largely unknown.
      Although metagenomic sequencing reveals microbial identities and functional gene
      information, it includes DNA from microbes with vastly varying physiological
      states. Therefore, metagenomics is only predictive of community functional
      potential. We posit that the next frontier lies in understanding the metaphenome,
      the product of the combined genetic potential of the microbiome and available
      resources. Here we describe examples of opportunities towards gaining
      understanding of the soil metaphenome.

PMID- 29454933
TI  - Effects of resting state condition on reliability, trait specificity, and network
      connectivity of brain function measured with arterial spin labeled perfusion MRI.
AB  - Resting state fMRI (rs-fMRI) provides imaging biomarkers of task-independent
      brain function that can be associated with clinical variables or modulated by
      interventions such as behavioral training or pharmacological manipulations. These
      biomarkers include time-averaged regional brain function as manifested by
      regional cerebral blood flow (CBF) measured using arterial spin labeled (ASL)
      perfusion MRI and correlated temporal fluctuations of function across brain
      networks with either ASL or blood oxygenation level dependent (BOLD) fMRI.
      Resting-state studies are typically carried out using just one of several
      prescribed state conditions such as eyes closed (EC), eyes open (EO), or visual
      fixation on a cross-hair (FIX), which may affect the reliability and specificity
      of rs-fMRI. In this study, we collected test-retest ASL MRI data during 4 resting
      state task conditions: EC, EO, FIX and PVT (low-frequency psychomotor vigilance
      task), and examined the effects of these task conditions on reliability and
      reproducibility as well as trait specificity of regional brain function. We also
      acquired resting-state BOLD fMRI under FIX and compared the network connectivity
      reliabilities between the four ASL conditions and the BOLD FIX condition. For
      resting-state ASL data, EC provided the highest CBF reliability, reproducibility,
      trait specificity, and network connectivity reliability, followed by EO, while
      FIX was lowest on all of these measures. PVT demonstrated lower CBF reliability,
      reproducibility and trait specificity than EO and EC. Overall network
      connectivity reliability was comparable between ASL and BOLD. Our findings
      confirm ASL CBF as a reliable, stable, and consistent measure of resting-state
      regional brain function and support the use of EC or EO over FIX and PVT as the
      resting-state condition.

PMID- 29454932
TI  - Preserved canonicality of the BOLD hemodynamic response reflects healthy
      cognition: Insights into the healthy brain through the window of Multiple
      Sclerosis.
AB  - The hemodynamic response function (HRF), a model of brain blood-flow changes in
      response to neural activity, reflects communication between neurons and the
      vasculature that supplies these neurons in part by means of glial cell
      intermediaries (e.g., astrocytes). Intact neural-vascular communication might
      play a central role in optimal cognitive performance. This hypothesis can be
      tested by comparing healthy individuals to those with known white-matter damage
      and impaired performance, as seen in Multiple Sclerosis (MS). Glial cell
      intermediaries facilitate the ability of neurons to adequately convey metabolic
      needs to cerebral vasculature for sufficient oxygen and nutrient perfusion. In
      this study, we isolated measurements of the HRF that could quantify the extent to
      which white-matter affects neural-vascular coupling and cognitive performance.
      HRFs were modeled from multiple brain regions during multiple cognitive tasks
      using piecewise cubic spline functions, an approach that minimized assumptions
      regarding HRF shape that may not be valid for diseased populations, and were
      characterized using two shape metrics (peak amplitude and time-to-peak). Peak
      amplitude was reduced, and time-to-peak was longer, in MS patients relative to
      healthy controls. Faster time-to-peak was predicted by faster reaction time,
      suggesting an important role for vasodilatory speed in the physiology underlying
      processing speed. These results support the hypothesis that intact neural-glial
      vascular communication underlies optimal neural and cognitive functioning.

PMID- 29454934
TI  - Time scale properties of task and resting-state functional connectivity:
      Detrended partial cross-correlation analysis.
AB  - Functional connectivity analysis is an essential tool for understanding brain
      function. Previous studies showed that brain regions are functionally connected
      through low-frequency signals both within the default mode network (DMN) and task
      networks. However, no studies have directly compared the time scale (frequency)
      properties of network connectivity during task versus rest, or examined how they
      relate to task performance. Here, using fMRI data collected from sixty-eight
      subjects at rest and during a stop signal task, we addressed this issue with a
      novel functional connectivity measure based on detrended partial cross
      correlation analysis (DPCCA). DPCCA has the advantage of quantifying correlations
      between two variables in different time scales while controlling for the
      influence of other variables. The results showed that the time scales of within
      network connectivity of the DMN and task networks are modulated in opposite
      directions across rest and task, with the time scale increased during rest vs.
      task in the DMN and vice versa in task networks. In regions of interest analysis,
      the within-network connectivity time scale of the pre-supplementary motor area -
      a medial prefrontal cortical structure of the task network and critical to
      proactive inhibitory control - correlated inversely with Barratt impulsivity and
      stop signal reaction time. Together, these findings demonstrate that time scale
      properties of brain networks may vary across mental states and provide evidence
      in support of a role of low frequency fluctuations of BOLD signals in behavioral
      control.

PMID- 29454935
TI  - Dynamic resting state fMRI analysis in mice reveals a set of Quasi-Periodic
      Patterns and illustrates their relationship with the global signal.
AB  - Time-resolved 'dynamic' over whole-period 'static' analysis of low frequency (LF)
      blood-oxygen level dependent (BOLD) fluctuations provides many additional
      insights into the macroscale organization and dynamics of neural activity.
      Although there has been considerable advancement in the development of mouse
      resting state fMRI (rsfMRI), very little remains known about its dynamic
      repertoire. Here, we report for the first time the detection of a set of
      recurring spatiotemporal Quasi-Periodic Patterns (QPPs) in mice, which show
      spatial similarity with known resting state networks. Furthermore, we establish a
      close relationship between several of these patterns and the global signal. We
      acquired high temporal rsfMRI scans under conditions of low (LA) and high (HA)
      medetomidine-isoflurane anesthesia. We then employed the algorithm developed by
      Majeed et al. (2011), previously applied in rats and humans, which detects and
      averages recurring spatiotemporal patterns in the LF BOLD signal. One type of
      observed patterns in mice was highly similar to those originally observed in
      rats, displaying propagation from lateral to medial cortical regions, which
      suggestively pertain to a mouse Task-Positive like network (TPN) and Default Mode
      like network (DMN). Other QPPs showed more widespread or striatal involvement and
      were no longer detected after global signal regression (GSR). This was further
      supported by diminished detection of subcortical dynamics after GSR, with
      cortical dynamics predominating. Observed QPPs were both qualitatively and
      quantitatively determined to be consistent across both anesthesia conditions,
      with GSR producing the same outcome. Under LA, QPPs were consistently detected at
      both group and single subject level. Under HA, consistency and pattern occurrence
      rate decreased, whilst cortical contribution to the patterns diminished. These
      findings confirm the robustness of QPPs across species and demonstrate a new
      approach to study mouse LF BOLD spatiotemporal dynamics and mechanisms underlying
      functional connectivity. The observed impact of GSR on QPPs might help better
      comprehend its controversial role in conventional resting state studies. Finally,
      consistent detection of QPPs at single subject level under LA promises a step
      forward towards more reliable mouse rsfMRI and further confirms the importance of
      selecting an optimal anesthesia regime.

PMID- 29454937
TI  - Frequency Modulation of Transcriptional Bursting Enables Sensitive and Rapid Gene
      Regulation.
AB  - Gene regulation is a complex non-equilibrium process. Here, we show that
      quantitating the temporal regulation of key gene states (transcriptionally
      inactive, active, and refractory) provides a parsimonious framework for analyzing
      gene regulation. Our theory makes two non-intuitive predictions. First, for
      transcription factors (TFs) that regulate transcription burst frequency, as
      opposed to amplitude or duration, weak TF binding is sufficient to elicit strong
      transcriptional responses. Second, refractoriness of a gene after a transcription
      burst enables rapid responses to stimuli. We validate both predictions
      experimentally by exploiting the natural, optogenetic-like responsiveness of the
      Neurospora GATA-type TF White Collar Complex (WCC) to blue light. Further, we
      demonstrate that differential regulation of WCC target genes is caused by
      different gene activation rates, not different TF occupancy, and that these rates
      are tuned by both the core promoter and the distance between TF-binding site and
      core promoter. In total, our work demonstrates the relevance of a kinetic, non
      equilibrium framework for understanding transcriptional regulation.

PMID- 29454936
TI  - Molecular Time Sharing through Dynamic Pulsing in Single Cells.
AB  - In cells, specific regulators often compete for limited amounts of a core
      enzymatic resource. It is typically assumed that competition leads to
      partitioning of core enzyme molecules among regulators at constant levels.
      Alternatively, however, different regulatory species could time share, or take
      turns utilizing, the core resource. Using quantitative time-lapse microscopy, we
      analyzed sigma factor activity dynamics, and their competition for RNA
      polymerase, in individual Bacillus subtilis cells under energy stress. Multiple
      alternative sigma factors were activated in ~1-hr pulses in stochastic and
      repetitive fashion. Pairwise analysis revealed that two sigma factors rarely
      pulse simultaneously and that some pairs are anti-correlated, indicating that
      RNAP utilization alternates among different sigma factors. Mathematical modeling
      revealed how stochastic time-sharing dynamics can emerge from pulse-generating
      sigma factor regulatory circuits actively competing for RNAP. Time sharing
      provides a mechanism for cells to dynamically control the distribution of cell
      states within a population. Since core molecular components are limiting in many
      other systems, time sharing may represent a general mode of regulation.

PMID- 29454938
TI  - Rare Cell Detection by Single-Cell RNA Sequencing as Guided by Single-Molecule
      RNA FISH.
AB  - Although single-cell RNA sequencing can reliably detect large-scale
      transcriptional programs, it is unclear whether it accurately captures the
      behavior of individual genes, especially those that express only in rare cells.
      Here, we use single-molecule RNA fluorescence in situ hybridization as a gold
      standard to assess trade-offs in single-cell RNA-sequencing data for detecting
      rare cell expression variability. We quantified the gene expression distribution
      for 26 genes that range from ubiquitous to rarely expressed and found that the
      correspondence between estimates across platforms improved with both
      transcriptome coverage and increased number of cells analyzed. Further, by
      characterizing the trade-off between transcriptome coverage and number of cells
      analyzed, we show that when the number of genes required to answer a given
      biological question is small, then greater transcriptome coverage is more
      important than analyzing large numbers of cells. More generally, our report
      provides guidelines for selecting quality thresholds for single-cell RNA
      sequencing experiments aimed at rare cell analyses.

PMID- 29454940
TI  - Perceptual load is not always a crucial determinant of early versus late
      selection.
AB  - The perceptual load hypothesis posits that early and late selection occurs under
      conditions of high and low perceptual load, respectively. Recent work, however,
      suggests that the absence of a congruency effect in high-load trials - the
      behavioral signature of early selection in studies of perceptual load - may not
      provide an exhaustive index of failing to identify task-irrelevant distractors.
      Prior research also suggests that the congruency sequence effect (CSE) - a
      modulation of the congruency effect after incongruent relative to congruent
      trials - provides complementary information about whether participants identify
      distractors. We therefore conducted a novel test of the perceptual load
      hypothesis that employed both the congruency effect and the CSE as measures of
      distractor identification. Experiment 1 revealed that distractors were identified
      not only in low-load trials but also in high-load trials wherein there was no
      overall congruency effect. Experiment 2 further revealed which task parameters
      allowed us to observe such "hidden" distractor identification. These findings
      suggest that perceptual load is not always a crucial determinant of early versus
      late selection.

PMID- 29454939
TI  - Comparative Analysis of Immune Cells Reveals a Conserved Regulatory Lexicon.
AB  - Most well-characterized enhancers are deeply conserved. In contrast, genome-wide
      comparative studies of steady-state systems showed that only a small fraction of
      active enhancers are conserved. To better understand conservation of enhancer
      activity, we used a comparative genomics approach that integrates temporal
      expression and epigenetic profiles in an innate immune system. We found that gene
      expression programs diverge among mildly induced genes, while being highly
      conserved for strongly induced genes. The fraction of conserved enhancers varies
      greatly across gene expression programs, with induced genes and early-response
      genes, in particular, being regulated by a higher fraction of conserved
      enhancers. Clustering of conserved accessible DNA sequences within enhancers
      resulted in over 60 sequence motifs including motifs for known factors, as well
      as many with unknown function. We further show that the number of instances of
      these motifs is a strong predictor of the responsiveness of a gene to pathogen
      detection.

PMID- 29454941
TI  - Characterization and electrochemical response of DNA functionalized 2nm gold
      nanoparticles confined in a nanochannel array.
AB  - Polyvalent gold nanoparticle oligonucleotide conjugates are subject of intense
      research. Even though 2nm diameter AuNPs have been previously modified with DNA,
      little is known about their structure and electrochemical behavior. In this work,
      we examine the influence of different surface modification strategies on the
      interplay between the meso-organization and the molecular recognition properties
      of a 27-mer DNA strand. This DNA strand is functionalized with different sulfur
      containing moieties and immobilized on 2nm gold nanoparticles confined on a
      nanoporous alumina, working the whole system as an electrode array. Surface
      coverages were determined by EXAFS and the performance as recognition elements
      for impedance-based sensors is evaluated. Our results prove that low DNA
      coverages on the confined nanoparticles prompt to a more sensitive response,
      showing the relevance in avoiding the DNA strand overcrowding. The system was
      able to determine a concentration as low as 100pM of the complementary strand,
      thus introducing the foundations for the construction of label-free genosensors
      at the nanometer scale.

PMID- 29454942
TI  - Cloning, molecular modeling and characterization of acidic cellulase from buffalo
      rumen and its applicability in saccharification of lignocellulosic biomass.
AB  - Cellulase hydrolyses the cellulose by cleaving the beta-1,4-linkages to produce
      mono-, oligo- and shorter polysaccharide units. These enzymes have applications
      in various industries such as pulp and paper, laundry, food and feed, textile,
      brewing industry and in biofuel production. In the present study we have cloned
      acid-cellulase gene (Cel-1) from the fosmid library of buffalo rumen metagenomic
      DNA and functionally expressed it in Escherichia coli. The ORF encoding cellulase
      consisted of 1176-bp, corresponding to protein of 391 amino acid and has
      catalytic domain belonging to glycosyl hydrolase family 5. The purified protein
      has a molecular weight of 43-kDa on SDS-PAGE and its expression was confirmed by
      western blotting. The tertiary structure of the cellulase (Cel-1) showed a
      classical (alpha/beta) TIM-like barrel motif. Model surface charge of Cel-1
      predicted that surface near active site was mostly negative which might be
      responsible for the stability of enzyme at lower pH. The pH and temperature for
      maximum enzyme activity were 4.5 and 45 degrees C respectively. Various metal
      ions enhanced the enzyme activity and in presence of Mn+2 activity was
      significantly increased. Cel-1 hydrolyzed pre-treated wheat straw and released
      reducing sugars (62.60%). These desirable properties of Cel-1 make it attractive
      for the bioconversion of biomass.

PMID- 29454943
TI  - Research of a new metal chelating carrier preparation and papain immobilization.
AB  - A new type of magnetic metal chelating carrier (PCMM-IDA-Cu2+) was prepared for
      the immobilization of papain, using chitosan as raw material, nano Fe3O4 as
      magnetic material, SiO2 as porogen, iminodiacetic acid (IDA) as a chelating
      ligand, and binding with transition metal ion (Cu2+). The resulting products were
      well characterized by optical microscopy, scanning electron microscopy (SEM),
      vibrating sample magnetometer (VSM), Fourier transform infrared spectroscopy
      (FTIR) and thermogravimetric analysis (TGA). The BBD (Box-Behnken Design) of RSM
      (Response Surface Methodology) was applied to analyze the optimum enzyme
      immobilization conditions. The results showed that the enzyme immobilization
      capacity was 94.18mg/g of PCMM-IDA-Cu2+, with 7.976U/mg of relative immobilized
      enzyme activity under the optimum conditions (pH6.73, 1.56mg enzyme/15.0mg
      carrier, 30.9 degrees C), and the recovery of enzyme activity was reached 87.21%.
      Compared with the free papain, the immobilized papain displayed enhanced enzyme
      activity, superior enzymatic properties, good operational stability and
      reusability. It is worth mentioning that the novel carriers exhibited selectively
      biological adsorption capacity, and this technique is an alternative method for
      the immobilization of enzyme, making the process more efficient and economic.

PMID- 29454944
TI  - Preparation, characterization and bioactivities of Athelia rolfsii
      exopolysaccharide-zinc complex (AEPS-zinc).
AB  - A new Athelia rolfsii exopolysaccharides (AEPS) were purified by Sephacryl S-300
      and S-200. The physicochemical characteristics of AEPS fractions were assayed by
      HPGPC and GC methods. The structures of AEPS and AEPS-zinc complex were
      characterized by SEM, FTIR and NMR. Moreover, the bioactivities of complex were
      also evaluated by experiments in vitro and in vivo. AEPSI consisted of glucose,
      galacturonic acid, talose, galactose, mannose and xylose, the relative contents
      of them were 24.74, 19.60, 33.65, 8.77, 7.97 and 5.28%, respectively. AEPSII
      consisted of glucose, inositol, galacturonic acid, ribitol, gluconic acid, talose
      and xylose, whose relative contents were 36.06, 21.21, 12.78, 11.07, 6.58, 5.45
      and 6.82%, respectively. The Mw and Mn of AEPSI were 6.1324*104 and 1.4218*104Da,
      those of AEPSII were 517 and 248Da. SEM observations showed that microstructures
      of AEPS and AEPS-zinc complex were obviously different both in size and shape.
      FTIR and NMR analysis indicated that AEPS might chelate with zinc ion through
      hydroxy and carboxy group. In vitro experiments showed that AEPS-zinc complex had
      a good bioavailability, in vivo experiments showed that it had good effect on
      improving zinc deficiency and antioxidant activities, which suggested that it
      could be used as zinc supplementation with high antioxidant activities.

PMID- 29454945
TI  - Dextran based herbal nanobiocomposite membranes for scar free wound healing.
AB  - Dextran based bionanocomposite membranes encapsulating clove oil (CO) and
      sandalwood oil (SO) that are capable of preventing infection due to their
      inherent virtue of antibacterial activity and modifying the wound healing cascade
      for accelerated scar free healing, were developed. A facile solvent casting
      technique was used to fabricate dextran/nanosoy/glycerol/chitosan (DNG/Ch)
      nanocomposite membranes followed by subsequent addition of CO and SO to obtain
      DNG/Ch/CO and DNG/Ch/SO herbal nanodressings. Dressings exhibited >98%
      antibacterial activity against both Staphylococcus aureus (S. aureus) and
      Escherichia coli (E. coli) at extremely low loadings of 5% and 10% for CO and SO,
      respectively. This encapsulation strategy allowed controlled diffusion of EO over
      a period of 72h which was measured in terms of drug efficacy using bacterial
      reduction count test and serial plate transfer disk diffusion test (SPTDDT).
      Swelling behavior and mechanical properties were also examined. Bacterial
      adherence study was performed to demonstrate the efficiency of dressings for
      arresting microbial invasion. In vivo wound healing studies were conducted using
      male swiss albino mice of BALB/c strain and DNG/Ch/CO dressings exhibited
      complete healing within 14days with remarkable efficacy in scar prevention.
      Histological analysis revealed that CO and SO treatment led to deposition of
      ordered collagen along with fibroblast migration.

PMID- 29454946
TI  - Changes of physical properties of PLA-based blends during early stage of
      biodegradation in compost.
AB  - Three biodegradable plastics materials, namely pure poly(l-lactide) (PLA), PLA
      with plasticizer triacetine (TAC) and the mixture PLA/polyhydroxybutyrate (PHB)
      and TAC were investigated concerning changes of physical properties due to
      biodegradation in compost at 58 degrees C up to 16days. With rising time of
      degradation in compost, both number and weight molecular masses were decreasing
      progressively, but only marginal change of the polydispersity index was observed
      which indicates that biodegradation is not random process. FTIR spectroscopy
      revealed that in spite of the extensive decrease of molecular weight, no
      substantial change in chemical composition was found. The most significant
      modification of the spectra consisted in an appearing of the broad band in region
      3100-3300cm-1, which was assigned to a formation of biofilm on the sample
      surfaces. This effect appeared for all three materials, however, it was much more
      pronounced for samples containing also triacetine. Measurement of changes in
      crystalline portion confirmed that amorphous phase degrades substantially faster
      compared to crystalline part. The plasticizer triacetine is disappearing also
      rather fast from the sample resulting besides other effect also in a temporary
      increase of Tg, which at the beginning grows almost to the value typical for PLA
      without plasticizer but later the Tg is decreasing due to substantial changes in
      molecular weight. Generally during composting, the samples keep shape for up to
      8days, after that time the material disintegrates to rough powder.

PMID- 29454947
TI  - Guide to electrospinning denatured whole chain collagen from hoki fish using
      benign solvents.
AB  - Tissue engineering requires the design and manufacture of biomimetic scaffolds.
      Collagen-derived nanofibrous scaffolds have been intensively studied because
      collagen, in the form of fibrils, is one of the main components of the extra
      cellular matrix (ECM). Several collagen materials have been used in
      electrospinning studies including mammalian extracted Type I collagen and gelatin
      formulations. Denatured whole chain collagen (DWCC) can be prepared by heat
      denaturing acid-soluble collagen extracted from cold-water fish skin. This
      product provides a consistent source of collagen with a controlled molecular
      weight profile and intact alpha chains including telopeptides. In this work, we
      studied DWCC-water-acid systems in order to determine the effect of solution
      composition on nanofibre morphology. Whereas measurement of the classical
      physical properties of concentrated solutions failed to predict and only
      partially explained the electrospinning behavior of collagen derived polymers,
      hydrodynamic properties provided insight. All the samples are presented in
      ternary diagrams to map the electrospinnability of the systems. These
      "electrospinning maps" provide an informative resource to electrospinning
      collagen-derived product for biomedical or commercial applications and a
      practical alternative to complicated models developed for synthetic polymers.

PMID- 29454948
TI  - Penaeus vannamei protease activating mechanism of sulfhydryl reducing compounds.
AB  - For the very first time, protease enzyme from Penaeus vannamei was investigated
      for its activation with thiol reductant compounds. The mechanism by which
      sulfhydryl reductant compounds enhances the activity of P. vannamei protease
      still remains unclear. In this study, it was discovered that thiol-reactive
      compounds increase P. vannamei protease activity by a factor of about 4 with
      increasing Vmax and decreasing Km parameters. Moreover, the reaction is an SN2
      type that does not require the initial binding of the thiol group of these
      compounds to the enzyme. Additionally, k2 increased appreciably with increasing
      concentration of sulfhydryl reductant compounds. The linearity of this plot
      indicates that k1 is unaffected by the addition of thiol compounds. Hence, the
      observed effect of thiol compounds on Km seems to be due to an increase in k2.
      These results suggest that the activation mechanism of P. vannamei protease
      almost certainly takes place by an SN2 reaction mechanism.

PMID- 29454949
TI  - Polyoxometalate-metal organic framework-lipase: An efficient green catalyst for
      synthesis of benzyl cinnamate by enzymatic esterification of cinnamic acid.
AB  - Iron-carboxylate (MIL-100(Fe)) and HKUST-1 (Cu3(BTC)2, BTC=1,3,5
      benzenetricarboxylic acid) as nanoporous metal organic framework supports were
      compared for immobilization of porcine pancreatic lipase (PPL). These
      immobilizations improved thermal, pH and operational stability of PPL compared to
      the soluble enzyme. Stability of MIL-100(Fe) was better than HKUST-1 as support.
      MIL-100(Fe) encapsulated Keggin phosphotungstic acid H3PW12O40 (PW) (PW@MIL
      100(Fe)) was synthesized to develop novel enzyme immobilized system and
      characterized by Fourier transform infrared spectroscopy (FT-IR), field emission
      scanning electron microscopy (FE-SEM), Brunauer-Emmett-Teller (BET), X-ray
      diffraction (XRD) and Barrett Joyner Halenda (BJH) analysis. Relative activity
      for immobilized lipase on PW@MIL-100(Fe) was more than MIL-100(Fe) in pH range of
      3-9. At the elevated temperature of 70 degrees C, the PW@MIL-100(Fe) was the most
      stable one. PW@MIL-100(Fe)/PPL substrate exhibited the higher stability at 4
      degrees C and 25 degrees C, along with other supports. Moreover, PW@MIL-100(Fe)
      was chosen as the best support for immobilization of PPL and was also applied for
      the synthesis of benzyl cinnamate by enzymatic esterification of cinnamic acid.
      The immobilized enzyme retained 90.4% of its initial activity during synthesis of
      benzyl cinnamate after 5 successive catalytic rounds and reached 80.0% yield
      after 8 reuses.

PMID- 29454951
TI  - The role of sucrose concentration in self-assembly kinetics of high methoxyl
      pectin.
AB  - Several natural and synthetic polysaccharides are able to form, under appropriate
      conditions, supramolecular structures, typically physical hydrogels, and,
      together with their biocompatibility, this explains their wide use in food,
      pharmaceutical and biomedical sectors. In the case of high methoxyl pectins (HMP)
      the gel formation is promoted by the presence of cosolutes (sugars or polyols)
      and low pH. The present investigation mainly regards the structuring kinetics of
      aqueous HMP solutions at acid pH (3.1) with the same pectin concentration (0.2%
      w/w) and different sucrose concentrations (from 56 to 65% w/w). Preliminary
      viscosity tests were performed to individuate the threshold of the sol region. A
      sequence of consecutive frequency sweeps was applied to each sample immediately
      after its preparation. The time evolution of the linear viscoelastic behavior is
      described by the sigmoidal profiles of both moduli at each applied frequency and
      more thoroughly defined through the change of the mechanical spectrum, i.e. the
      variation of the parameters of the generalized Maxwell model or the Friedrich
      Braun model which are both suitable to provide a satisfactory data fitting. In
      particular, the equilibrium modulus Ge offers a significant description of the
      gelation kinetics and its sucrose dependence.

PMID- 29454950
TI  - Producing novel edible films from semi refined carrageenan (SRC) and ulvan
      polysaccharides for potential food applications.
AB  - Edible films were developed from seaweed polysaccharides (Kappaphycus alvarezii
      and Ulva fasciata). The total extracted yield of semi refined carrageenan (SRC)
      and ulvan polysaccharide was 31.55%, and 28.86%, with total carbohydrate being
      78.08% and 82.43% in SRC and ulvan polysaccharides. Results of viscometric
      studies revealed molecular weight to be 210kDa and 72kDa for SRC and ulvan
      polysaccharides. Proton NMR studies showed presence of anhydro-d-galactopyranose
      and glucosidic linkages in SRC, while ulvan polysaccharide had rhamnose-3
      sulfate, glucosyl and beta-d-glucuronic acid. Three different films developed
      from SRC and ulvan polysaccharides [SRC, ulvan polysaccharide and combination of
      SRC and ulvan polysaccharide films] with glycerol. FT-IR spectra confirmed
      functional group of all the edible films which corresponds with NMR results.
      Water vapor permeability of films indicated a range of 7.82 to 9.96*10-8gm-1s-1Pa
      1 with high tensile strength varying between 36.78 and 49.12MPa. Results on
      antioxidant activity indicated a strong hydroxyl radical scavenging activity
      detected in ulvan polysaccharide based film, while metal ion chelating activity
      was higher in films with a combination of SRC and ulvan polysaccharides. Further,
      low molecular weight films had better antioxidant activity, while high molecular
      weight films possessed good mechanical properties.

PMID- 29454952
TI  - Probing the interaction of the phytochemical 6-gingerol from the spice ginger
      with DNA.
AB  - 6-Gingerol [5-hydroxy-1-(4-hydroxy-3-methoxyphenyl) decan-3-one], the bio-active
      ingredient of the popular Indian spice ginger (Zingiber officinale Roscoe), is
      well-known for its pharmacological and physiological actions. The potent
      antioxidant, antiemetic, antiulcer, antimicrobial, analgesic, hypoglycemic,
      antihypertensive, antihyperlipidemic, immunostimulant, anti-inflammatory,
      cardiotonic, and cancer prevention activities of 6-Gingerol has been investigated
      and explored. 6-Gingerol is a good candidate for the treatment of various cancers
      including prostrate, pancreatic, breast, skin, gastrointestinal, pulmonary, and
      renal cancer. In this study we report for the first time the molecular
      recognition of 6-Gingerol with calf thymus DNA (ctDNA) through experimental and
      molecular modeling techniques confirming a minor groove binding mode of 6
      Gingerol with ctDNA. Fluorescence and UV-vis spectroscopic studies confirm the
      complex formation of 6-gingerol with ctDNA. The energetics and thermodynamics of
      the interaction of 6-Gingerol with ctDNA was explored by Isothermal Titration
      Calorimetry (ITC) and Differential Scanning Calorimetry (DSC). The ctDNA helix
      melting upon 6-Gingerol binding was examined by melting temperature Tm analysis.
      Further the electrophoretic mobility shift assay confirms a possible groove
      binding of 6-Gingerol with ctDNA. Molecular docking and Molecular dynamics (MD)
      studies provide a detailed understanding on the interaction of 6-Gingerol binding
      in the minor groove of DNA which supports experimental results.

PMID- 29454953
TI  - Non-active site mutation (Q123A) in New Delhi metallo-beta-lactamase (NDM-1)
      enhanced its enzyme activity.
AB  - New Delhi metallo beta-lactamase-1 is one of the carbapenemases, causing
      hydrolysis of almost all beta-lactamase antibiotics. Seventeen different NDM
      variants have been reported so far, they varied in their sequences either by
      single or multiple amino acid substitutions. Hence, it is important to understand
      its structural and functional relation. In the earlier studies role of active
      site residues has been studied but non-active site residues has not studied in
      detail. Therefore, we have initiated to further comprehend its structure and
      function relation by mutating some of its non-active site residues. A laboratory
      mutant of NDM-1 was generated by PCR-based site-directed mutagenesis, replacing Q
      to A at 123 position. The MICs of imipenem and meropenem for NDM-1Q123A were
      found increased by 2 fold as compare to wild type and so the hydrolytic activity
      was enhanced (Kcat/Km) as compared to NDM-1 wild type. GOLD fitness scores were
      also found in favour of kinetics data. Secondary structure for alpha-helical
      content was determined by Far-UV circular dichroism (CD), which showed
      significant conformational changes. We conclude a noteworthy role of non-active
      site amino acid residues in the catalytic activity of NDM-1. This study also
      provides an insight of emergence of new variants through natural evolution.

PMID- 29454954
TI  - Preparation and characterization of C-phycocyanin peptide grafted N-succinyl
      chitosan by enzyme method.
AB  - C-phycocyanin peptide (CPC) grafted N-succinyl chitosan (NSC) was prepared via
      the catalysis of Microbial transglutaminase (MTGase). The single factor
      experiment displayed that the degree of substitution (DS) of N-succinyl chitosan
      C-phycocyanin peptide (NSC-CPC) depended on the reaction time, the reaction
      temperature and the reaction pH value. The CS, synthesized NSC and NSC-CPC were
      characterized by Fourier transform infrared spectroscopy (FT-IR). NSC-CPC showed
      excellent moisture absorption and retention ability. In vitro antioxidant
      activity assays demonstrated that, with the DS and concentration increasing of
      NSC-CPC, the scavenging activity of 1,1-Diphenyl-2-pic-rylhydrazyl (DPPH) radical
      and hydroxyl radical increased. The methylthiazol tetrazolium (MTT) essay
      demonstrated that NSC-CPC inhibited Hela cells while promoted the proliferation
      of L929 mouse fibroblasts. In conclusion, these results suggested the potential
      application of NSC-CPC in pharmaceutical and biomedical fields.

PMID- 29454955
TI  - Physicochemical properties of starch adhesives enhanced by esterification
      modification with dodecenyl succinic anhydride.
AB  - Starch-based adhesives were prepared by esterification modification with
      dodecenyl succinic anhydride (DDSA) and polyaryl polymethylene isocyanate (PAPI)
      as a crosslinking agent. DDSA modified starch (DMS) adhesives could significantly
      enhance the viscosity and adhesion strength of starch adhesives, making it
      beneficial to be applied in the field of plywood industry. This paper
      investigated the physicochemical properties of starch modified by dodecenyl
      succinic anhydride. Solid content, viscosity, adhesion, structural change and
      morphological features were characterized in detail. Viscosity and solid content
      of the modified starch (MF) adhesives was improved remarkably when DDSA was
      introduced. Three-ply plywood was fabricated with DMS adhesives, and its wet
      shear strength was measured. The results showed that the water resistance of the
      adhesive with 6wt% DDSA improved by 72.4% compared to that without DDSA. The wet
      shear strength plywood bonded by the adhesive reached 1MPa and could meet the
      requirement set by the China National Standard. Incorporating DDSA into the
      starch adhesive formed a dense crosslinking structure due to chemical reactions
      between DDSA and active groups on the starch molecules and thus improve the water
      resistance of the cured adhesives. The introduction of DDSA improving the
      viscosity and solid content remarkably, which increased the amount of the
      adhesive that penetrated the wood surface and formed more interlocks. Using DDSA
      promoted a smooth and homogeneous fracture surface of cured adhesive, which
      effectively prevented water intrusion and improved water resistance. The modified
      adhesive proved practical as a plywood adhesive for industrial application.

PMID- 29454956
TI  - De novo transcriptome assembly and analysis of differential gene expression
      following peptidoglycan (PGN) challenge in Antheraea pernyi.
AB  - Antheraea pernyi is not only an important economic insect, it is increasingly
      employed as a model organism due to a variety of advantages, including ease of
      rearing and experimental manipulation compared with other Lepidoptera.
      Peptidoglycan (PGN) is a major component of the bacterial cell wall, and
      interactions between PGN and A. pernyi cause a series of physiological changes in
      the insect. In the present study, we constructed cDNA libraries from a A. pernyi
      PGN-infected group and a control group stimulated with phosphate-buffered saline
      (PBS). The transcriptome was de novo assembled using the Trinity platform, and
      1698 differentially expressed genes (DEGs) were identified, comprising 894 up
      regulated and 804 down-regulated genes. To further investigate immune-related
      DEGs, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)
      enrichment were performed. GO analysis identified major immune-related GO terms
      and KEGG enrichment indicated gene responses to three pathways related to the
      insect immune system. Several homologous genes related to the immune response of
      the A. pernyi fat body post-PGN infection were identified and categorised. Taken
      together, the results provide insight into the complex molecular mechanisms of
      the responses to bacterial infection at the transcriptional level.

PMID- 29454958
TI  - Clinical Features and Surgical Management of Cerebellopontine Angle Cholesteatoma
      That Presented as Trigeminal Neuralgia.
AB  - BACKGROUND: It is difficult to differentiate patients with cerebellopontine angle
      (CPA) cholesteatoma and patients with primary trigeminal neuralgia just according
      to early symptoms. We aimed to explore the clinical characteristics, early
      diagnosis, and microneurosurgical techniques for CPA cholesteatoma that presented
      as trigeminal neuralgia. METHODS: The data of 26 patients who complained
      trigeminal neuralgia with CPA cholesteatoma between January 2009 and December
      2015 were collected and studied retrospectively, they were diagnosed by magnetic
      resonance imaging preoperatively and confirmed by pathology postoperatively. All
      the tumors were resected through a retrosigmoidal approach. In 26 cases, 14
      patients who underwent cholesteatoma resection and microvascular decompression
      were assigned to group A and 12 patients who underwent only cholesteatoma
      resection were assigned to group B. The clinical features and surgical results
      between groups A and B were compared. The complications and surgical results were
      followed up, and surgical techniques were summarized. RESULTS: All patients
      presented as trigeminal neuralgia at the same side of the cholesteatoma. There
      was no statistical difference between the 2 groups in clinical features and
      surgical results between groups A and B. All patients with cholesteatoma showed
      clear and significant imaging characteristics. The tumors were totally removed in
      18 patients and subtotally removed in 8 patients. Pain relief was satisfactory in
      all patients. Surgical complications included transient aseptic meningitis in 2
      patients, facial numbness in 2 patients, mild tinnitus in 2 patients, mild and
      facial weakness in 1 patient. No death, hematoma, or acute hydrocephalus were
      reported in this series. During the follow-up of 12-80 months, no patient
      experienced recurrence of pain or tumor. CONCLUSIONS: Cholesteatoma of the
      cerebellopontine angle often presented as trigeminal neuralgia. Magnetic
      resonance imaging is helpful for early diagnosis according to its distinct
      signal. Surgical treatment is often the first choice, the neuralgia relief was
      satisfactory after operation. Microvascular decompression is recommended
      simultaneously if some offending vessels were founded during the surgical
      resection of the tumor.

PMID- 29454957
TI  - Mixed selectivity encoding and action selection in the prefrontal cortex during
      threat assessment.
AB  - The medial prefrontal cortex (mPFC) regulates expression of emotional behavior.
      The mPFC combines multivariate information from its inputs, and depending on the
      imminence of threat, activates downstream networks that either increase or
      decrease the expression of anxiety-related motor behavior and autonomic
      activation. Here, we selectively highlight how subcortical input to the mPFC from
      two example structures, the amygdala and ventral hippocampus, help shape mixed
      selectivity encoding and action selection during emotional processing. We outline
      a model where prefrontal subregions modulate behavior along orthogonal motor
      dimensions, and exhibit connectivity that selects for expression of one
      behavioral strategy while inhibiting the other.

PMID- 29454959
TI  - Exophytic Cerebral Hemispheric Low-Grade Glioma: Unusual Growth Pattern of Common
      Central Nervous System Tumor.
AB  - BACKGROUND: Exophytic growth (EG), wherein the tumor mass grows beyond the
      neuraxial boundary formed by pia mater, remains a rare pattern of glioma growth.
      It has been described in gliomas at several locations like the brainstem,
      cerebellum, suprasellar area, spinal cord, and insula. However, EG in hemispheric
      grade 2 astrocytomas, particularly affecting the convexity subarachnoid space, as
      against the more spacious basal subarachnoid space, is exceedingly rare. To the
      best of our knowledge, there is only 1 such case reported in the English
      literature. Due to the extreme rarity, little is known about these tumors,
      particularly the mechanisms underlying the EG and their possible clinical
      implications. CASE DESCRIPTION: A 32-year-old woman presented with partial motor
      seizures without any neurologic signs. On magnetic resonance imaging of the head,
      a nonenhancing, T2-hyperintense, right frontal lobe lesion was noted. The
      majority of the lesion was occupying the adjacent subdural space while still
      remaining in continuity with the intra-axial globular component. During surgery,
      the exophytic nature of the lesion was confirmed. We performed maximal resection
      of the exophytic portion with subtotal excision of the intra-axial component. She
      recovered uneventfully after surgery and subsequently received external beam
      radiotherapy for the residual tumor. CONCLUSION: Although extremely rare,
      cerebral hemispheric grade 2 astrocytomas may have an EG pattern. The exact
      mechanisms underlying this are not clearly known. More such cases need to be
      reported so that we can decipher the true nature of these tumors.

PMID- 29454960
TI  - Case of Subarachnoid Hemorrhage from Ruptured Oncotic Fusiform Aneurysms from
      Choriocarcinoma Metastasis Treated with Aneurysmectomy and Vessel Reconstruction.
AB  - BACKGROUND: Oncotic aneurysm is a rare condition with a high mortality rate.
      Because no consensus has been reached regarding therapeutic strategy for ruptured
      oncotic aneurysm, treatment remains challenging. CASE DESCRIPTION: A 35-year-old
      woman developed sudden onset of severe headache. Computed tomography showed
      subarachnoid hemorrhage and cerebral angiography revealed 2 fusiform aneurysms in
      the distal portion of the left middle cerebral artery. Aneurysmectomy with vessel
      reconstruction using a superficial temporal artery graft was performed to
      maintain blood flow to the distal middle cerebral artery. Pathologic examination
      of the aneurysm and wall of the resected recipient middle cerebral artery showed
      infiltrating trophoblasts. Immunostaining for human chorionic gonadotropin was
      positive in the aneurysm specimen. On the basis of an elevated concentration of
      serum human chorionic gonadotropin, choriocarcinoma with ruptured intracranial
      oncotic aneurysms was diagnosed. After further systemic examination for
      carcinoma, chemotherapy was initiated. CONCLUSIONS: Aneurysmectomy, resection of
      the parent artery with irregular walls and reconstruction to the distal recipient
      artery with normal intima should be considered to secure patency of the
      anastomosis and prevent the recurrence of oncotic aneurysm. Subsequent
      chemotherapy is essential to prevent carcinomatous meningitis and disease
      progression.

PMID- 29454961
TI  - First-line anti-tuberculosis drugs induce hepatotoxicity: A novel mechanism based
      on a urinary metabolomics platform.
AB  - Tuberculosis (TB) has become a global public health and social threat. As
      clinical first-line drugs, rifampicin and isoniazid used in combination with
      pyrazinamide and ethambutol (the HRZE regimen) usually induce hepatotoxicity.
      However, the mechanisms underlying this phenomenon remain unclear, and studying
      the metabolic impact of co-treating TB patients with the HRZE regimen can provide
      new hepatotoxicity evidence. In this study, urine metabolites from TB patients
      were profiled using a high-resolution ultra-performance liquid chromatography
      mass spectrometry (UPLC-MS) platform. The tricarboxylic acid circulation,
      arginine and proline metabolism and purine metabolic pathways were found to be
      affected by anti-TB drugs. The levels of pyroglutamate, isocitrate, citrate, and
      xanthine were significantly decreased after the administration of HRZE. The above
      mentioned pathways were also different between drug-induced liver injury (DILI)
      and non-DILI patients. Urate and cis-4-octenedioic acid levels in the DILI group
      were significantly increased compared to those in the non-DILI group, while the
      cis-aconitate and hypoxanthine levels were significantly decreased. These results
      highlight that superoxide generation can aggravate the hepatotoxic effects of the
      HRZE regimen. In addition, our metabolomic approach had the ability to predict
      hepatotoxicity for clinical applications.

PMID- 29454962
TI  - The high bone mass phenotype of Lrp5-mutant mice is not affected by megakaryocyte
      depletion.
AB  - Bone remodeling is a continuously ongoing process mediated by bone-resorbing
      osteoclasts and bone-forming osteoblasts. One key regulator of bone formation is
      the putative Wnt co-receptor Lrp5, where activating mutations in the
      extracellular domain cause increased bone formation in mice and humans. We have
      previously reported that megakaryocyte numbers are increased the bone marrow of
      mice carrying a high bone mass mutation (HBM) of Lrp5 (Lrp5G170V). Since
      megakaryocytes can promote bone formation, we addressed the question, if the bone
      remodeling phenotype of Lrp5G170V mice is affected by megakaryocyte depletion.
      For that purpose we took advantage of a mouse model carrying a mutation of the
      Mpl gene, encoding the thrombopoietin receptor. These mice (Mplhlb219) were
      crossed with Lrp5G170V mice to generate animals carrying both mutations in a
      homozygous state. Using MUCT, undecalcified histology and bone-specific
      histomorphometry of 12 weeks old littermates we observed that megakaryocyte
      number was remarkably decreased in Mplhlb219/Lrp5G170V mice, yet the high bone
      mass phenotype of Lrp5G170V mice was not significantly affected by the homozygous
      Mpl mutation. Finally, when we analyzed 24 weeks old wildtype and Mplhlb219 mice
      we did not observe a statistically significant alteration of bone remodeling in
      the latter ones. Taken together, our results demonstrate that an increased number
      of bone marrow megakaryocytes does not contribute to the increased bone formation
      caused by Lrp5 activation.

PMID- 29454963
TI  - Adenosine receptors enhance the ATP-induced odontoblastic differentiation of
      human dental pulp cells.
AB  - Purinergic signaling regulates various biological processes through the
      activation of adenosine receptors (ARs) and P2 receptors. ATP induces the
      odontoblastic differentiation of human dental pulp cells (HDPCs) via P2
      receptors. However, there is no information available about the roles of ARs in
      HDPC odontoblastic differentiation induced by ATP. Here, we found that HDPCs
      treated with ATP showed higher activity of ADORA1 (A1R), ADORA2B (A2BR), and
      ADORA3 (A3R). Inhibition of A1R and A2BR attenuated ATP-induced odontoblastic
      differentiation of HDPCs, whereas activation of the two receptors enhanced the
      odontoblastic differentiation induced by ATP. However, activation of ARs by
      adenosine did not induce the odontoblastic differentiation of HDPCs independently
      without induction of ATP. Our study indicates a positive role for ARs in ATP
      induced odontoblastic differentiation of HDPCs, and demonstrates that ATP-induced
      odontoblastic differentiation of HDPCs may be due to the combined administration
      of ARs and P2 receptors. This study provides new insights into the molecular
      mechanisms of pulpal injury repair induced by ATP.

PMID- 29454964
TI  - NEK3-mediated SNAP29 phosphorylation modulates its membrane association and SNARE
      fusion dependent processes.
AB  - Intracellular membrane fusion depends on the presence of specific mediators, the
      vesicle (v-) and the target (t-) SNAREs (Soluble N-ethylmaleimide-sensitive
      factor, NSF, attachment protein SNAP receptors), whose interaction brings
      apposing membranes to close proximity and initiates their fusion. SNAP29
      (synaptosomal-associated protein 29), a t-SNARE protein, is involved in multiple
      fusion events during intracellular transport and affects structure of organelles
      such as the Golgi apparatus and focal adhesions. Mutations in SNAP29 gene result
      in CEDNIK (Cerebral dysgenesis, neuropathy, ichthyosis and palmoplantar
      keratoderma) syndrome. In the present study, we show that NEK3 (NIMA-never in
      mitosis gene A-related kinase 3)-mediated serine 105 (S105) phosphorylation of
      SNAP29 directs its membrane association, without which cells present defective
      focal adhesion formation, impaired Golgi structure and attenuated cellular
      recycling. In contrast to a phosphorylation-defective serine 105 to alanine
      (S105A) mutant, wildtype SNAP29, partially rescued the abnormal morphology of a
      CEDNIK patient derived fibroblasts. Our results highlight the importance of NEK3
      mediated S105 phosphorylation of SNAP29 for its membrane localization and for
      membrane fusion dependent processes.

PMID- 29454965
TI  - Detection of synchronized burst firing in cultured human induced pluripotent stem
      cell-derived neurons using a 4-step method.
AB  - Human induced pluripotent stem cell-derived neurons are promising for use in
      toxicity evaluations in nonclinical studies. The multi-electrode array (MEA)
      assay is used in such evaluation systems because it can measure the
      electrophysiological function of a neural network noninvasively and with high
      throughput. Synchronized burst firing (SBF) is the main analytic parameter of
      pharmacological effects in MEA data, but an accurate method for detecting SBFs
      has not been established. In this study, we present a 4-step method that
      accurately detects a target SBF confirmed by the researcher's interpretation of a
      raster plot. This method calculates one set parameter per step, in the following
      order: the inter-spike interval (ISI), the number of spikes in an SBF, the inter
      SBF interval, and the number of spikes in an SBF again. We found that the 4-step
      method is advantageous over the conventional method because it determines the
      preferable duration of an SBF, accurately distinguishes continuous SBFs, detects
      weak SBFs, and avoids false detection of SBFs. We found also that pharmacological
      evaluations involving SBF analysis may differ depending on whether the 4-step or
      conventional threshold method is used. This 4-step method may contribute to
      improving the accuracy of drug toxicity and efficacy evaluations using human
      induced pluripotent stem cell-derived neurons.

PMID- 29454966
TI  - Effects of PQ's cytotoxicity on secretory vesicles in astroglia: Expression
      alternation of secretogranin II and its potential interaction with intracellular
      factors.
AB  - It has been extensively characterized that paraquat (PQ) selectively targets to
      the substantia nigra and exerts neurotoxic actions on dopaminergic neurons.
      However, a little knowledge is available about astroglia in PQ exposure,
      especially its complex secretory machinery. To explore this point, we built up a
      PQ-induced model in cultural U118 astrocyte. Since the granin family is
      considered as a master regulator of cargo sorting and large dense core vesicles
      (LDCVs) biogenesis in the regulated secretory pathway of nervous and
      neuroendocrine cells, the current study focused on one member, secretogranin II
      (SCG2) and investigated its alternation and potential relationship with other
      astrocyte-derived factors under PQ insult. We found that PQ upregulated SCG2
      expression on both RNA and protein levels and stimulated the mRNA expression of
      neurotrophic factors, cytokines and glutamine synthetase (GS) simultaneously.
      RNAi knockdown of SCG2 did not rescue the cell cycle arrest induced by PQ but
      affected expressions of IL-6 and GS on mRNA and protein levels. Further studies
      on subcellular location showed that SCG2-positive secretory granules were
      partially colocalized with IL-6 but not GS in PQ exposure astrocyte. Taken
      together, our findings indicate that the expression alternation of SCG2 under
      astroglial activation by PQ may be necessary compensation for cargo sorting and
      LDCV biogenesis. The involvement of the IL-6 and GS suggests that the SCG2 may
      potentially regulate inflammatory factors and excitatory neurotransmitter to the
      cytotoxicity of PQ on astroglia.

PMID- 29454967
TI  - SARM1 deletion restrains NAFLD induced by high fat diet (HFD) through reducing
      inflammation, oxidative stress and lipid accumulation.
AB  - SARM1 (Sterile alpha and armadillo motif-containing protein 1) is the recently
      identified TIR domain-containing cytosolic protein, which is involved in toll
      like receptors (TLRs) signaling transduction. In the present study, the role of
      SARM1 in high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD)
      progression was explored. We found that SARM1 was expressed highly in fatty
      liver. And SARM1-knockout (KO) reduced steatohepatitis and metabolic disorders
      induced by HFD. SARM1-deletion decreased aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) levels in HFD-fed mice. Additionally, inflammatory
      response caused by HFD was alleviated by SARM1-deletion through inactivating
      TLR4/7/9 and nuclear factor kappa B (NF-kappaB) pathways. Of note, SARM1-deletion
      also reduced the expressions of inflammation-associated molecules in hypothalamus
      of HFD-fed mice. Furthermore, HFD administration led to oxidative stress in liver
      of mice, while being decreased in SARM1-KO mice. Moreover, SARM1-ablation
      improved lipid dyslipidemia by suppressing the mRNA levels of genes, linked to
      glycolysis, lipogenesis and transcriptional regulation. Insulin resistance was
      also attenuated by SARM1-deficiency through enhancing the activation of liver
      Akt/glycogen synthase kinase-3beta (GSK3beta) and insulin receptor substrate-1
      (IRS1)/FOXO1 pathways in HFD-fed mice. Also, SARM1-knockout improved neuropeptide
      Y (NPY), Pro-Opiomelanocortins (POMC), Agouti-related Protein (AGRP) and Cocaine
      and-Amphetamine Responsive Transcript 1 (CART1) expressions in hypothalamus of
      mice after HFD administration. In vitro, we found that the reduction of
      inflammatory response, oxidative stress and dyslipidemia induced by SARM1
      knockout in primary hepatocytes after fructose stimulation was largely attributed
      to its suppression to TLR4/7/9. Together, the findings demonstrated that SARM1
      might be an effective target for developing effective therapeutic strategies
      against NAFLD.

PMID- 29454968
TI  - Ess2 bridges transcriptional regulators and spliceosomal complexes via distinct
      interacting domains.
AB  - Transcription and pre-mRNA splicing are complex, coupled processes that involve
      transcriptional co-regulators. Ess2 (also termed Dgcr14) is a nuclear protein
      that enhances the transcriptional activity of retinoic acid receptor-related
      orphan receptor gamma/gamma-t (Rorgamma/gammat). Ess2 is also a component of the
      spliceosomal C complex (containing U2, U5 and U6 snRNAs). However, the domains in
      Ess2 that function in splicing and transcription have not been identified. To
      elucidate the roles of Ess2 in splicing and transcription, we performed RNA
      immunoprecipitation (RIP) assays to detect Ess2-interacting snRNAs. We found that
      Ess2 associated with U6 snRNA as well as U1 and U4 snRNAs. Experiments using Ess2
      deletion mutants showed that a C-terminus deletion mutant of Ess2 (1-399 a. a.)
      lost its ability to associate with snRNAs, whereas the N-terminus domain of Ess2
      (1-200 a. a.) associated with Rorgamma/gammat, but not with snRNAs.
      Interestingly, experiments using anti-ROR common antibody showed that Rors also
      associated with U4 and U6 snRNAs. Ess2 knockdown in a T cell hybridoma (68-41
      cells) abrogated the interaction between spliceosomes and Rors. An Ess2-dependent
      association was also found between an lncRNA (Rmrp) and Rors. We thus propose
      that Ess2 associates with both transcriptional factors and spliceosomal complexes
      and modulates splicing reactions coupled with transcription factors.

PMID- 29454970
TI  - Increased cerebrospinal fluid complement C5 levels in major depressive disorder
      and schizophrenia.
AB  - Inflammation has been implicated in a variety of psychiatric disorders. We aimed
      to determine whether levels of complement C5 protein in the cerebrospinal fluid
      (CSF), which may reflect activation of the complement system in the brain, are
      altered in patients with major psychiatric disorders. Additionally, we examined
      possible associations of CSF C5 levels with clinical variables. Subjects
      comprised 89 patients with major depressive disorder (MDD), 66 patients with
      bipolar disorder (BPD), 96 patients with schizophrenia, and 117 healthy controls,
      matched for age, sex, and ethnicity (Japanese). Diagnosis was made according to
      the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria.
      CSF C5 levels were measured by enzyme-linked immunosorbent assay. CSF C5 levels
      were significantly increased in the patients with MDD (p < 0.001) and in the
      patients with schizophrenia (p = 0.001), compared with the healthy controls. The
      rate of individuals with an "abnormally high C5 level" (i.e., above the 95th
      percentile value of the control subjects) was significantly increased in all
      psychiatric groups, relative to the control group (all p < 0.01). Older age, male
      sex, and greater body mass index tended to associate with higher C5 levels. There
      was a significantly positive correlation between C5 levels and chlorpromazine
      equivalent dose in the patients with schizophrenia. Thus, we found, for the first
      time, elevated C5 levels in the CSF of patients with major psychiatric disorders.
      Our results suggest that the activated complement system may contribute to
      neurological pathogenesis in a portion of patients with major psychiatric
      disorders.

PMID- 29454969
TI  - JIP3 knockout protects mice against high fat diet-induced liver injury.
AB  - Multiple pathways contribute to nonalcoholic fatty liver disease (NAFLD) in
      response to high fat diets (HFD). A homolog of mammalian JNK-interacting protein
      3 (JIP3), also known as JSAP-1, activates different components in various
      signaling pathways to modulate cellular processes. The purpose of this study was
      to examine the role of JIP3 in obesity-related pathologies pathway. Wild-type
      (WT) C57BL/6 and JIP3-knockout (JIP3-/-) mice were randomized to chow or HFD. HFD
      fed WT mice increased hepatic JIP3 expression. Mice lacking JIP3 exhibited
      reduced weight gain, hepatic steatosis, insulin resistance, lipid accumulation,
      oxidative stress and inflammatory response in mice fed a HFD, which were,
      importantly, dependent on various signaling pathways. Lipogenesis-linked pathway
      was inhibited in JIP3-/- mice after HFD, while PPARalpha/gamma were increased.
      Additionally, JIP3-/- inhibited hepatic oxidative stress, evidenced by down
      regulation of total reactive oxygen species (ROS), H2O2, O2.-, malondialdehyde
      (MDA), xanthine oxidase (XO), inducible nitric oxide synthase (iNOS), and up
      regulation of superoxide dismutase (SOD) and total antioxidant capacity (TAC) in
      mice after HFD feeding, which might be related to nuclear respiratory factor 2
      (Nrf-2) pathway activation. Further, inflammatory response was blocked in JIP3-/-
      mice fed with HFD. The process might be attributed to the suppression of toll
      like receptors (TLRs), p-nuclear factor kappa B (NF-kappaB) and p-c-Jun-N
      terminal kinase (JNK). Thus, JIP3 absence is associated with decreased
      lipogenesis, oxidative stress and inflammation, supplying a new target for NAFLD
      treatment.

PMID- 29454971
TI  - Overexpression of PtABCC1 contributes to mercury tolerance and accumulation in
      Arabidopsis and poplar.
AB  - Mercury (Hg) is a highly biotoxic heavy metal that contaminates the environment.
      Phytoremediation is a green technology for environmental remediation and is used
      to clean up Hg contaminated soil in recent years. In this study, we isolated an
      ATP-binding cassette (ABC) transporter gene PtABCC1 from Populus trichocarpa and
      overexpressed it in Arabidopsis and poplar. The transgenic plants conferred
      higher Hg tolerance than wild type (WT) plants, and overexpression of PtABCC1
      could lead to 26-72% or 7-160% increase of Hg accumulation in Arabidopsis or
      poplar plants, respectively. These results demonstrated that PtABCC1 plays a
      crucial role in enhancing tolerance and accumulation to Hg in plants, which
      provides a promising way for phytoremediation of Hg contamination.

PMID- 29454972
TI  - Enhanced Recovery After Surgery Pathway in Patients Undergoing Open Radical
      Cystectomy Is Safe and Accelerates Bowel Function Recovery.
AB  - OBJECTIVE: To assess whether an Enhanced Recovery After Surgery pathway was
      associated with a faster bowel function recovery and no increase in morbidity
      compared with standard perioperative care in a contemporary series of patients
      undergoing radical cystectomy. METHODS: A prospective single-center single
      surgeon cohort of 114 consecutive patients treated with open radical cystectomy
      between July 2013 and June 2016 was analyzed. A study group of 74 patients with
      Enhanced Recovery After Surgery pathway was compared with a control group of 40
      patients with standard perioperative care. Primary outcome was recovery of bowel
      function, measured by resumption of bowel sounds, passage of flatus, and passage
      of stool. Secondary outcome was rate of overall and major 90-day postoperative
      complications. RESULTS: Bowel function recovery was significantly faster in the
      study group. Resumption of bowel sounds on postoperative day 1 was recorded in 43
      (58%) vs 4 (10%) patients, passage of flatus within postoperative day 2 in 41
      (55%) vs 11 (28%) patients, and passage of stool within postoperative day 3 in 37
      (50%) vs no patients in the study vs control group, respectively (P < .01 for
      all). Overall and major 90-day complications were observed in 35 (47.3%) and 13
      (17.6%) patients in the study group, and in 25 (62.5%) and 9 (22.5%) patients in
      the control group (P = .14 and 0.38, respectively). CONCLUSION: In patients
      undergoing open radical cystectomy, an Enhanced Recovery After Surgery pathway
      allowed a significantly faster bowel function recovery with no increase in 90-day
      postoperative complications compared with standard perioperative care.

PMID- 29454973
TI  - Comparison of dual mobility total hip arthroplasty and bipolar arthroplasty for
      femoral neck fractures: A retrospective case-control study of 199 hips.
AB  - BACKGROUND: The choice between performing total hip arthroplasty (THA) or
      hemiarthroplasty (HA) is not straightforward in older patients with femoral neck
      fracture, particularly when co-morbidities are factored in. This led us to carry
      out a case-control study to determine (1) the rate of mechanical complications
      for these two types of implants, and (2) the rate of medical complications and
      mortality. HYPOTHESIS: THA with dual mobility cup (DM) will result in fewer
      mechanical complications than HA. PATIENTS AND METHODS: This was a single-center,
      retrospective case-control study. Between 2010 and 2015, all patients with a
      femoral neck fracture treated by HA or DM THA were included. The primary outcome
      was the occurrence of any type of surgical complication. The Charlson Co
      morbidity Index (CCI) and the independence during Activities of Daily Living
      (ADL) score were calculated for every patient. Two subgroups of patients were
      made based on whether they met frailty criteria. The effect of covariates on 1
      year mortality was controlled using Cox's proportional hazards regression model.
      RESULTS: The cohort consisted of 101 HA and 98 THA procedures in 193 patients
      (139 women, 54 men) with a mean age of 80.6years (range, 76-101). The mean follow
      up was 24.2months (range, 0-83) with a median of 14.5months. Fifteen of the HA
      hips (15%) had surgical complication, of which 10 were posterior dislocations
      (10%). Ten patients in the HA cohort had a serious medical complication (10%).
      Ten of the THA hips (10%) had a mechanical complication, including three
      posterior dislocations (3%) and four infections (4%). Nine patients in the THA
      cohort had a medical complication (9%). There were significantly fewer posterior
      dislocations in the THA hips (p = 0.05). In the subgroup analysis, the 117
      patients (58%) who met the frailty criteria had a significantly lower dislocation
      rate after undergoing THA (p = 0.048). After adjusting on age, ADL and CCI score,
      the dislocation rate no longer differed significantly between the two groups (p =
      0.1). The dislocation rate was lower in the THA hips only in the "frail" patients
      (Odds ratio = 0.137, 95% CI: [0.003-0.97] (p = 0.04)). There was no difference in
      the dislocation rate in the "non-frail" patients. The overall 1-year mortality
      was 85% [95% CI: 78-94%]. It was 78% [95% CI: 69-86%] for the HA hips and 88%
      [95% CI: 82-95%] for the THA hips (p = 0.01). After factoring in the impact of
      age, CCI and ADL, the differences in the 1-year mortality between HA and THA were
      no longer present (p = 0.42). Thus, there is no increased risk of mortality in
      THA patients. DISCUSSION: When the CCI and independence level are taken into
      consideration, the frailest patients can undergo DM THA to reduce the dislocation
      risk, without increasing the mortality rate at 1year. Patients who are not frail
      will benefit equally from undergoing HA or THA. LEVEL OF EVIDENCE: III, case
      control study.

PMID- 29454974
TI  - Proof of patient information: Analysis of 201 judicial decisions.
AB  - INTRODUCTION: The ruling by the French Court of Cassation dated February 25, 1997
      obliged doctors to provide proof of the information given to patients, reversing
      more than half a century of case law. In October 1997, it was specified that such
      evidence could be provided by "all means", including presumption. No hierarchy in
      respect of means of proof has been defined by case law or legislation. The
      present study analyzed judicial decisions with a view to determining the means of
      proof liable to carry the most weight in a suit for failure to provide due
      patient information. MATERIAL AND METHOD: A retrospective qualitative study was
      conducted for the period from January 2010 to December 2015, by a search on the
      LexisNexis(r) JurisClasseur website. Two hundred and one judicial decisions
      relating to failure to provide due patient information were selected and analyzed
      to study the characteristics of the practitioners involved, the content of the
      information at issue and the means of proof provided. The resulting cohort of
      practitioners was compared with the medical demographic atlas of the French Order
      of Medicine, considered as exhaustive. RESULTS: Two hundred and one practitioners
      were investigated for failure to provide information: 45 medical practitioners
      (22+/-3%), and 156 surgeons (78+/-3%) including 45 orthopedic surgeons (29+/-3.6%
      of surgeons). Hundred and ninety-three were private sector (96+/-1.3%) and 8
      public sector (4+/-1.3%). Hundred and one surgeons (65+/-3.8% of surgeons), and
      26 medical practitioners (58+/-7.4%) were convicted. Twenty-five of the 45
      orthopedic surgeons were convicted (55+/-7.5%). There was no significant
      difference in conviction rates between surgeons and medical practitioners: odds
      ratio, 1.339916; 95% CI [0.6393982; 2.7753764] (Chi2 test: p=0.49). Ninety-two
      practitioners based their defense on a single means of proof, and 74 of these
      were convicted (80+/-4.2%). Forty practitioners based their defense on several
      means of proof, and 16 of these were convicted (40+/-7.8%). There was a
      significant difference in conviction rate according to reliance on single or
      multiple evidence of delivery of information: odds ratio, 0.165; 95% CI [0.07;
      0.4] (Chi2 test: p=1.1*10-5). DISCUSSION: This study shows that surgeons, and
      orthopedic surgeons in particular, are more at risk of being investigated for
      failure to provide due patient information (D=-0.65 [-0.7; -0.6]). They are not,
      however, more at risk of conviction (p=0.49). Being in private practice also
      appeared to be a risk factor for conviction of failure to provide due
      information. Offering several rather than a single means of proof of delivery of
      information significantly reduces the risk of conviction (p=1.1*10-5). LEVEL OF
      EVIDENCE: Level IV: Retrospective study.

PMID- 29454975
TI  - Prefrontal cortex activation during obstacle negotiation: What's the effect size
      and timing?
AB  - BACKGROUND: Obstacle negotiation is a daily activity that requires the
      integration of sensorimotor and cognitive information. Recent studies provide
      evidence for the important role of prefrontal cortex during obstacle negotiation.
      We aimed to explore the effects of obstacle height and available response time on
      prefrontal activation. METHODS: Twenty healthy young adults (age: 30.1 +/- 1.0
      years; 50% women) walked in an obstacle course while negotiating anticipated and
      unanticipated obstacles at heights of 50 mm and 100 mm. Prefrontal activation was
      measured using a functional near-infrared spectroscopy system. Kinect cameras
      measured the obstacle negotiation strategy. Prefrontal activation was defined
      based on mean level of HbO2 before, during and after obstacle negotiation and the
      HbO2 slope from gait initiation and throughout the task. Changes between types of
      obstacles were assessed using linear-mix models and partial correlation analyses
      evaluated the relationship between prefrontal activation and the distance between
      the feet as the subjects traversed the obstacles. RESULTS: Different obstacle
      heights showed similar changes in prefrontal activation measures (p > 0.210).
      However, during unanticipated obstacles, the slope of the HbO2 response was
      steeper (p = 0.048), as compared to anticipated obstacles. These changes in
      prefrontal activation during negotiation of unanticipated obstacles were
      correlated with greater distance of the leading foot after the obstacles (r =
      0.831, p = 0.041). CONCLUSIONS: These findings are the first to show that the
      pattern of prefrontal activation depends on the nature of the obstacle. More
      specifically, during unanticipated obstacles the recruitment of the prefrontal
      cortex is faster and greater than during negotiating anticipated obstacles. These
      results provide evidence of the important role of the prefrontal cortex and the
      ability of healthy young adults to tailor the activation pattern to different
      types of obstacles.

PMID- 29454976
TI  - Defective Endogenous Pain Modulation in Fibromyalgia: A Meta-Analysis of Temporal
      Summation and Conditioned Pain Modulation Paradigms.
AB  - : To study the characteristics of temporal summation (TS) and conditioned pain
      modulation (CPM) in fibromyalgia (FM) patients, we systematically searched Pubmed
      and EMBASE for studies using TS or CPM comparing FM patients with healthy
      controls. We computed Hedges' g, risk of bias, sensitivity analysis, and meta
      regression tests with 10,000 Monte-Carlo permutations. Twenty-three studies (625
      female and 23 male FM patients and 591 female and 81 male healthy controls) were
      included. The meta-analyses showed an effect size of .53 for TS (P < .001; 95%
      confidence interval = .23-.83), which is a 68% relative difference between
      patients and controls, and of .57 for CPM (P < .001; 95% confidence interval = 
      .88 to -.26), representing a 65% relative difference between the groups. The
      qualitative analyses revealed large heterogeneity between study protocols.
      Although studies were of low risk of bias, lack of blinding was substantial.
      Sensitivity analysis and meta-regression identified type and site of stimulation,
      age, lab, sample size, and medication control as important sources of between
      study variability. We showed a significant alteration of pain modulation
      mechanisms in FM patients. PERSPECTIVE: This novel meta-analysis provides
      evidence for defective endogenous pain modulation in FM patients. We explored the
      effect of covariates on between-study variability in these paradigms. These
      biomarkers may aid in diagnosis, and treatment of patients. However, validation
      requires further investigation under strict methodological settings, and into
      individual patient covariates.

PMID- 29454977
TI  - Neural networks in bottom up 'experiential emotion regulation'.
AB  - Emotion regulation is thought to differ in when and how it influence emotion,
      well being and representation in the brain. While previous research on ER has
      focused on gray matter correlates, this study represents the first exploratory
      study on white matter integrity of brain networks of ER. Responding to the gap
      between cognitive and affective approaches of ER, pertaining to some of the daily
      emotional stressors, the present study investigates a complementary experiential
      approach such as 'Emotional approach' or the tendency to affectively acknowledge,
      understand and express emotional experience (cf. Stanton et al., 2000). Diffusion
      tensor magnetic resonance imaging (DTI-MRI) measures of fractional anisotropy
      (FA) and mean diffusivity (MD) evaluated dispositional ER in a group of 21 women
      with (1) a 'high emotional approach' (HEA) (N = 11) and (2) a 'low emotional
      approach' (LEA) (N = 10). HEA exhibited more FA of the cingulum supporting
      emotion processing and emotion regulation, whereas LEA showed a higher FA in the
      right corticospinal tracts supporting automatic action tendencies and together
      with a higher FA in the superior longitudinal fasciculus (SLF), cognitive control
      tasks and monitoring of emotion. LEA also correlated with a significant increase
      in MD in the body (p. = 0.05) and in the splenium of the corpus callosum (CC). A
      higher FA in the inferior longitudinal fasciculus (IFL) may indicate higher
      visual- affective integration within emotion processing, whereas more MD in the
      body and splenium of the CC decreases the interhemispheric integration of
      emotional information within emotion processing and emotion regulation.

PMID- 29454978
TI  - Ribonucleotide reductase as a drug target against drug resistance Mycobacterium
      leprae: A molecular docking study.
AB  - Leprosy is a chronic infection of skin and nerve caused by Mycobacterium leprae.
      The treatment is based on standard multi drug therapy consisting of dapsone,
      rifampicin and clofazamine. The use of rifampicin alone or with dapsone led to
      the emergence of rifampicin-resistant Mycobacterium leprae strains. The emergence
      of drug-resistant leprosy put a hurdle in the leprosy eradication programme. The
      present study aimed to predict the molecular model of ribonucleotide reductase
      (RNR), the enzyme responsible for biosynthesis of nucleotides, to screen new
      drugs for treatment of drug-resistant leprosy. The study was conducted by
      retrieving RNR of M. leprae from GenBank. A molecular 3D model of M. leprae was
      predicted using homology modelling and validated. A total of 325 characters were
      included in the analysis. The predicted 3D model of RNR showed that the phi and
      phi angles of 251 (96.9%) residues were positioned in the most favoured regions.
      It was also conferred that 18 alpha-helices, 6 beta turns, 2 gamma turns and 48
      helix-helix interactions contributed to the predicted 3D structure. Virtual
      screening of Food and Drug Administration approved drug molecules recovered 1829
      drugs of which three molecules, viz., lincomycin, novobiocin and telithromycin,
      were taken for the docking study. It was observed that the selected drug
      molecules had a strong affinity towards the modelled protein RNR. This was
      evident from the binding energy of the drug molecules towards the modelled
      protein RNR (-6.10, -6.25 and -7.10). Three FDA-approved drugs, viz., lincomycin,
      novobiocin and telithromycin, could be taken for further clinical studies to find
      their efficacy against drug resistant leprosy.

PMID- 29454979
TI  - Variants of TLR1 associated with tuberculosis susceptibility in the Chinese
      Tibetan population but not in Han Chinese.
AB  - Toll-like receptor 1 (TLR1) participates in the innate immune response to
      Mycobacterium tuberculosis. This study mainly investigated the relationship
      between polymorphisms of TLR1 and tuberculosis (TB) susceptibility in the two
      Chinese populations. Totally, 1185 Han and 1216 Tibetan participants were
      enrolled. TagSNPs of TLR1 were selected and genotyped. Analyses of linkage
      disequilibrium and haplotypes were performed by software Haploview and SHEsis.
      Gene-gene interactions were evaluated using the nonparametric multifactor
      dimensionality reduction (MDR) method. Gene-by-sex interaction in the Tibetan
      population and gene-by-smoking interaction in the Han population were also
      calculated. Association between rs4833095 and TB susceptibility was evaluated by
      meta-analysis. In the Tibetan population, the A alleles of rs5743557 and
      rs5743596 were related with reduced tuberculosis risk (p < 0.001 and p = 0.001)
      after adjusting for confounding factors. Additionally, rs5743604_A was associated
      with increased TB susceptibility (p = 0.004). The frequency of haplotype
      rs4833095-rs5743557-rs5743596-rs5743604 CAAG was significantly higher in the
      healthy controls (HC) group (p = 0.0009), while frequency of haplotype CGGA was
      higher in the TB group (p = 0.001). Significant associations were detected
      between rs4833095-rs5743557-rs5743604 interactions and TB susceptibility.
      Interactions between rs5743596 and sex in the Tibetan population, between
      rs5743604 and smoking in the Han population were revealed as well. However, no
      significant main effects were observed in the Han population. The rs4833095 was
      not associated with TB susceptibility after meta-analysis either. Our study
      suggested that SNPs of the TLR1 gene were associated with TB susceptibility in
      the Chinese Tibetan population, but not in the Han population.

PMID- 29454981
TI  - Natural products as inhibitors of prostaglandin E2 and pro-inflammatory 5
      lipoxygenase-derived lipid mediator biosynthesis.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostanoid formation and
      represent prevalent therapeutics for treatment of inflammatory disorders.
      However, NSAIDs are afflicted with severe side effects, which might be
      circumvented by more selective suppression of pro-inflammatory eicosanoid
      biosynthesis. This concept led to dual inhibitors of microsomal prostaglandin E2
      synthase (mPGES)-1 and 5-lipoxygenase that are crucial enzymes in the
      biosynthesis of pro-inflammatory prostaglandin E2 and leukotrienes. The potential
      of their dual inhibition in light of superior efficacy and safety is discussed.
      Focus is placed on natural products, for which direct inhibition of mPGES-1 and
      leukotriene biosynthesis has been confirmed.

PMID- 29454980
TI  - Cumulative incidence of suicidal ideation and associated factors among adults
      living in temporary housing during the three years after the Great East Japan
      Earthquake.
AB  - BACKGROUND: The effect of disasters on suicidality is not known. We aimed to
      retrospectively determine the cumulative incidence of suicidal ideation during
      the 3 years after the Great East Japan Earthquake among residents in temporary
      housing without prior suicidal ideation, as compared to the general population.
      Moreover, we aimed to identify the risk factors for the onset of suicidal
      ideation. METHODS: A cross-sectional survey involving face-to-face interviews was
      conducted 3 years after the earthquake with adult community residents in disaster
      affected areas and a control area using the World Health Organization Composite
      International Diagnostic Interview version 3.0. We compared the cumulative
      incidence of suicidal ideation between the two areas using the Cox proportional
      hazard model and examined risk factors for the onset of suicidal ideation using a
      multiple logistic regression analysis. RESULTS: Among 1019 respondents in the
      disaster-affected areas, the cumulative incidence of suicidal ideation over 1, 2,
      and 3 years after the earthquake was 1.4%, 2.4%, and 2.8%, respectively, which
      was significantly higher than that in the control area. Not being married, being
      injured in the disaster, and poor subjective physical health were associated with
      the onset of suicidal ideation. LIMITATIONS: We estimated the time of onset of
      suicidal ideation based on the respondents' current age and self-reported onset
      age, which limits the accuracy of the onset timing. CONCLUSIONS: We revealed a
      higher incidence of suicidal ideation in temporary housing residents and
      identified several risk factors, which suggests the importance of developing
      countermeasures to prevent suicide after a disaster.

PMID- 29454982
TI  - Improved genomic resources and new bioinformatic workflow for the carcinogenic
      parasite Clonorchis sinensis: Biotechnological implications.
AB  - Clonorchis sinensis (family Opisthorchiidae) is an important foodborne parasite
      that has a major socioeconomic impact on ~35 million people predominantly in
      China, Vietnam, Korea and the Russian Far East. In humans, infection with C.
      sinensis causes clonorchiasis, a complex hepatobiliary disease that can induce
      cholangiocarcinoma (CCA), a malignant cancer of the bile ducts. Central to
      understanding the epidemiology of this disease is knowledge of genetic variation
      within and among populations of this parasite. Although most published molecular
      studies seem to suggest that C. sinensis represents a single species, evidence of
      karyotypic variation within C. sinensis and cryptic species within a related
      opisthorchiid fluke (Opisthorchis viverrini) emphasise the importance of studying
      and comparing the genes and genomes of geographically distinct isolates of C.
      sinensis. Recently, we sequenced, assembled and characterised a draft nuclear
      genome of a C. sinensis isolate from Korea and compared it with a published draft
      genome of a Chinese isolate of this species using a bioinformatic workflow
      established for comparing draft genome assemblies and their gene annotations. We
      identified that 50.6% and 51.3% of the Korean and Chinese C. sinensis genomic
      scaffolds were syntenic, respectively. Within aligned syntenic blocks, the
      genomes had a high level of nucleotide identity (99.1%) and encoded 15 variable
      proteins likely to be involved in diverse biological processes. Here, we review
      current technical challenges of using draft genome assemblies to undertake
      comparative genomic analyses to quantify genetic variation between isolates of
      the same species. Using a workflow that overcomes these challenges, we report on
      a high-quality draft genome for C. sinensis from Korea and comparative genomic
      analyses, as a basis for future investigations of the genetic structures of C.
      sinensis populations, and discuss the biotechnological implications of these
      explorations.

PMID- 29454983
TI  - Old and new glycopeptide antibiotics: From product to gene and back in the post
      genomic era.
AB  - Glycopeptide antibiotics are drugs of last resort for treating severe infections
      caused by multi-drug resistant Gram-positive pathogens. First-generation
      glycopeptides (vancomycin and teicoplanin) are produced by soil-dwelling
      actinomycetes. Second-generation glycopeptides (dalbavancin, oritavancin, and
      telavancin) are semi-synthetic derivatives of the progenitor natural products.
      Herein, we cover past and present biotechnological approaches for searching for
      and producing old and new glycopeptide antibiotics. We review the strategies
      adopted to increase microbial production (from classical strain improvement to
      rational genetic engineering), and the recent progress in genome mining,
      chemoenzymatic derivatization, and combinatorial biosynthesis for expanding
      glycopeptide chemical diversity and tackling the never-ceasing evolution of
      antibiotic resistance.

PMID- 29454984
TI  - Adenovirus-mediated OX40Ig gene transfer induces long-term survival of orthotopic
      liver allograft in rats.
AB  - BACKGROUND: To discuss the effect and mechanism of adenovirus-mediated OX40Ig
      gene transfer in inducing long-term survival of liver allografts in rats.
      METHODS: Orthotopic liver transplantation was performed from Lewis to Brown
      Norway (BN) rats through the modified two-cuffed technique, and all rats were
      randomly divided equally into four groups: control, AdEGFP, AdOX40Ig, and FK506.
      The survival times of the rats were recorded. The rats' liver function, serum
      cytokines, hepatocyte pathology, OX40Ig protein level, and mixed lymphocyte
      reaction (MLR) with or without recombinant interleukin-2 (rIL-2) were evaluated.
      RESULTS: Compared with the control and AdEGFP groups, the rats in the AdOX40Ig
      and FK506 groups survived longer (P < 0.05), experienced less damage to hepatic
      function (P < 0.05), and showed milder hepatic cellular rejection and less
      hepatic cellular apoptosis. Interferon (IFN)-gamma and IL-2 content in the serum
      were lower after operation (P < .05) in the AdOX40Ig and FK506 groups. On the
      contrary, IL-4 and IL-10 content in the serum was higher after operation (P <
      0.05) in the AdOX40Ig and FK506 groups. OX40Ig protein was significantly
      expressed in the AdOX40Ig group and reached the highest level on the 7th day
      after operation. With respect to the MLR between BN and Lewis rats, the AdOX40Ig
      group showed a lighter reaction for the same strain than the control and AdEGFP
      groups (P < 0.05), which is different from the MLR between BN and F344 rats.
      After adding rIL-2 to the MLR system between BN rats in the AdOX40Ig group and
      Lewis rats, MLR was aggravated. CONCLUSION: Through OX40/OX4OL pathways, OX40Ig
      created an immunosuppressive effect after liver transplantation in rats. This
      immunosuppressive effect is associated with reduced IL-2 and can be reversed by
      adding IL-2 with antigen specificity.

PMID- 29454985
TI  - A non-toxic microbial surfactant from Marinobacter hydrocarbonoclasticus SdK644
      for crude oil solubilization enhancement.
AB  - This study aims to investigate the ability of a biosurfactant produced by
      Marinobacter hydrocarbonoclasticus strain SdK644 isolated from hydrocarbon
      contaminated sediment to enhance the solubilization rate of crude oil
      contaminated seawater. Phylogenetic analysis shows that strain SdK644 was very
      closely related to M. hydrocarbonoclasticus with 16S rRNA gene sequence
      similarity of 97.44%. Using waste frying oil as inducer carbon source, the
      producing biosurfactant by strain SdK644 was applied to improve crude oil
      solubilization in seawater. The preliminary characterization of the produced
      biosurfactant by FT-IR analysis indicates its possible classification in a
      glycolipids group. Results from crude oil solubilization assay showed that SdK644
      strain biosurfactant was 2-fold greater than Tween 80 surfactant in crude oil
      solubilization and 12-fold higher than seawater control, as shown by GC-MS
      analysis of aliphatic compounds. Furthermore, this bioactive compound was shown
      to be nontoxic against Artemia larvae in short-term acute toxicity bioassay.
      Generally, the results showed the possible use of M. hydrocarbonoclasticus strain
      SdK644 biosurfactant in bioremediation processes of the marine environments.

PMID- 29454986
TI  - Nano-sized TiO2 (nTiO2) induces metabolic perturbations in Physarum polycephalum
      macroplasmodium to counter oxidative stress under dark conditions.
AB  - Nano-sized TiO2 (nTiO2) exerts an oxidative effect on cells upon exposure to
      solar or UV irradiation and ecotoxicity of the nTiO2 is an urgent concern. Little
      information is available regarding the effect of TiO2 on cells under dark
      conditions. Metabolomics is a unique approach to the discovery of biomarkers of
      nTiO2 cytotoxicity, and leads to the identification of perturbed metabolic
      pathways and the mechanism underlying nTiO2 toxicity. In the present study, gas
      chromatography mass spectrometry (GC/MS)-based metabolomics was performed to
      investigate the effect of nTiO2 on sensitive cells (P. polycephalum
      macroplasmodium) under dark conditions. According to the multivariate pattern
      recognition analysis, at least 60 potential metabolic biomarkers related to sugar
      metabolism, amino acid metabolism, nucleotide metabolism, polyamine biosynthesis,
      and secondary metabolites pathways were significantly perturbed by nTiO2.
      Notably, many metabolic biomarkers and pathways were related to anti-oxidant
      mechanisms in the living organism, suggesting that nTiO2 may induce oxidative
      stress, even under dark conditions. This speculation was further validated by the
      biochemical levels of reactive oxygen species (ROS), 8-hydroxy-2-deoxyguanosine
      (8-OHdG), and total soluble phenols (TSP). We inferred that the oxidative stress
      might be related to nTiO2-induced imbalance of cellular ROS. To the best of our
      knowledge, the present study is the first to investigate the nTiO2-induced
      metabolic perturbations in slime mold, provide a new perspective of the mechanism
      underlying nTiO2 toxicity under dark conditions, and show that metabolomics can
      be employed as a rapid, reliable and powerful tool to investigate the interaction
      among organisms, the environment, and nanomaterials.

PMID- 29454987
TI  - Nature differences of humic acids fractions induced by extracted sequence as
      explanatory factors for binding characteristics of heavy metals.
AB  - The composition and structure of Humic acid (HA) is so heterogeneous that it
      brings significant barriers to investigate the interaction between HA and heavy
      metal ions. The isolation of HA with relatively homogeneity is a key to reveal
      the binding mechanisms between HA and heavy metals. In this work, ten HA
      fractions (HAs) were obtained by sequential alkali extraction procedure and
      nature differences of the extracted HAs were considered as explanatory factors
      for binding characteristics of Cu2+, Pb2+ and Cd2+. The results indicate that
      more large molecular weight (MW) HA subunits, less carboxyl and phenolic group
      contents, weaker aromaticity and polarity were measured with increasing
      extractions, inducing weaker binding capacity of HAs. Ligand binding and bi
      Langmuir models indicated that the sorption capacity and binding affinity of
      earlier extracted HAs were higher than the latter ones. The peak area changes at
      3427, 1599, and 619 cm-1 pre- and post-adsorption in FTIR spectra suggested
      carboxyl, phenolic and nitrogen-containing groups were involved in the adsorption
      process. At the same time, the peak area difference between HAs and HAs-metal
      (DeltaS) of phenolic groups were 8.22-20.50, 6.81-21.11 and 10.66-19.80% for
      Cu2+, Pb2+ and Cd2+, respectively, DeltaS of carboxyl groups 6.64-17.03, 8.96
      16.82 and 9.45-17.85% for Cu2+, Pb2+ and Cd2+, respectively, DeltaS of nitrogen
      containing groups 0.33-0.48, 0.20-1.38 and 0.31-0.59% for Cu2+, Pb2+ and Cd2+,
      respectively. DeltaS of phenolic and carboxyl groups were larger than those of
      nitrogen-containing groups, implying that these two groups were the predominant
      binding sites suppliers for metal ions, which were also supported by the results
      of correlation analysis. This work is helpful to insight the environmental
      impacts of natural organic matter and the fate of heavy metals in natural
      environment.

PMID- 29454988
TI  - Effect of Bacillus subtilis and NTA-APG on pyrene dissipation in phytoremediation
      of nickel co-contaminated wetlands by Scirpus triqueter.
AB  - A complex mix of organic pollutants and heavy metal made the remediation of
      contaminated wetlands more difficult. Few research focus on the remediation for
      pyrene enhanced by chemical reagents and pyrene degrading bacteria in the nickel
      co-contaminated soil. In this paper, the effect of chemical reagents
      (nitrilotriacetic acid and alkyl polyglucoside) and Bacillus subtilis on pyrene
      dissipation in phytoremediation of nickel co-contaminated soil by Scirpus
      triqueter was investigated. Similar seedlings of Scirpus triqueter were moved to
      uncontaminated soil and pyrene-nickel co-contaminated soil. The pots (14.8 cm
      diameter and 8.8 cm height) were set up in greenhouse and treated in different
      ways. After 60 days, plant biomass, radial oxygen loss (ROL), soil dehydrogenase
      activity (DHA) and pyrene concentration in soil were determined. Results showed
      that ROL rate and DHA in different groups was positively correlated with pyrene
      dissipation from soil. In the process of remediation, chemical reagents might
      have an indirect slight effect on pyrene dissipation (pyrene dissipation
      increased 21%) by affecting DHA firstly and redistributing pyrene fractions in
      the presence of pyrene degrading bacteria. Pyrene degrading bacteria were likely
      to affect pyrene dissipation by impacting ROL rate and DHA and played a more
      vital role in contributing to pyrene dissipation (pyrene dissipation increased
      45%) from wetland. This study demonstrated that phytoremediation for pyrene in
      nickel co-contaminated soil by Scirpus triqueter can be enhanced by the
      application of NTA-APG and pyrene degrading bacteria and they could be reasonably
      restore the ecological environment of PAH-contaminated wetlands.

PMID- 29454989
TI  - One year study of PM2.5 in Xinxiang city, North China: Seasonal characteristics,
      climate impact and source.
AB  - This study was conducted in order to explore the seasonal characteristics,
      climate impact and source of PM2.5 in Xinxiang, China. Daily PM2.5 samples were
      collected at urban site from January to December in 2015. Average PM2.5
      concentration was 100.6 +/- 65.8 MUg m-3 in Xinxiang, which was several times
      higher than China Ambient Air Quality Standards (GB3095-2012). Secondary
      inorganic aerosols (SIA) constituted 70% of the total ionic concentrations. The
      average concentration of SO42- was 6.4 +/- 12.0 MUg m-3, which ranked the highest
      among the water-soluble ions analyzed. Seasonal variations of PM2.5 and its major
      chemical components were significant, most of them with high values in winter and
      the lowest values in summer, especially with heavier PM2.5 events (more than 200
      MUg/m3) in December. SIA and OC on polluted days were 2.1-2.3 times higher than
      those of on clean days. It was estimated that Fe, Li, Na, Mg, Al, K, Ca and Sr
      were emitted from crustal sources and Pb, Cr, Ni, Cu, Zn, As, Cd and V were
      emitted from anthropogenic emissions using the EF values. Analysis using the
      tracer and PCA/MLR revealed that vehicle exhausts were the most important source
      of PM2.5, which contributed 26.9% of PM2.5 over the whole study period. This
      study provides detailed composition data and first comprehensive analysis of
      PM2.5 in Xinxiang during a whole year.

PMID- 29454990
TI  - Sorption kinetics, isotherms, and mechanism of aniline aerofloat to agricultural
      soils with various physicochemical properties.
AB  - Aniline aerofloat (AAF), a high-toxic organic flotation reagent, is widely used
      in mineral processing industry. However, little information on its environmental
      fate is available. AAF sorption to four types of agricultural soils at low
      concentrations (1-10 mg/L) was investigated using batch experiments. AAF sorption
      kinetics involved both boundary layer diffusion and intraparticle diffusion,
      following pseudo-second-order kinetics with equilibrium time within 120 min. Both
      Langmuir and Freundlich models fitted well the AAF sorption with the former
      better. Sorption of AAF to soils was a spontaneous and favorable physical
      sorption that was controlled by ion bridge effect and hydrophobic interaction
      that was related to van der Waals force and pi-pi coordination based on FTIR
      analyses. AAF sorption was remarkably affected by soil constituents, positively
      correlating with the contents of organic matter and clay. The relatively higher
      logKoc values (3.53-4.66) of AAF at environmental concentrations (1-5 mg/L) imply
      that soils are serving as a sink of AAF from beneficiation wastewater, posing
      great potential risks to environment and human health.

PMID- 29454991
TI  - Toxicological effect of underutilized plant, Cleistanthus collinus leaf extracts
      against two major stored grain pests, the rice weevil, Sitophilus oryzae and red
      flour beetle, Tribolium castaneum.
AB  - Toxicity and repellency activity of Cleistanthus collinus (Roxb.) (CC) leaf
      extracts were evaluated against rice weevil, Sitophilus oryzae (L.) and red flour
      beetle, Tribolium castaneum (Herbst) under laboratory condition. Five
      concentration(s) (1%, 1.5%, 2%, 2.5% and 4%) with two controls (acetone and
      water) treatments along with deltamethrin were used for direct and contact
      residual toxicity. The insect that survived after CC exposure were transferred to
      an untreated feeding substrate and the population buildup of subsequent two
      generation were recorded after 30 (F1) and 60 days (F2). In the contact residual
      toxicity, highest CC concentration (4%) produced 75% mortality in S. oryzae and
      62.5% mortality in T. castaneum during 7 days of exposure, whereas in direct
      toxicity the mortality were 81% and 58% respectively, for S. oryzae and T.
      castaneum. The long term effect of CC was apparent in both the insect species,
      where F2 populations were significantly decreased in the CC treatments. CC
      treatment at 4% produced similar adult mortality in comparison to deltamethrin at
      1%. In addition, repellent activity of CC extracts was observed against both S.
      oryzae and T. castaneum. This is the first step towards assessing the scientific
      basis for the understanding the effectiveness of CC extracts against stored grain
      pests and it could be a viable eco-friendly option for stored grain insect pest
      management.

PMID- 29454992
TI  - A novel beta-glucosidase isolated from the microbial metagenome of Lake Poraque
      (Amazon, Brazil).
AB  - The Amazon region holds most of the biological richness of Brazil. Despite their
      ecological and biotechnological importance, studies related to microorganisms
      from this region are limited. Metagenomics leads to exciting discoveries, mainly
      regarding non-cultivable microorganisms. Herein, we report the discovery of a
      novel beta-glucosidase (glycoside hydrolase family 1) gene from a metagenome from
      Lake Poraque in the Amazon region. The gene encodes a protein of 52.9 kDa, named
      AmBgl-LP, which was recombinantly expressed in Escherichia coli and biochemically
      and structurally characterized. Although AmBgl-LP hydrolyzed the synthetic
      substrate p-nitrophenyl-beta-d-glucopyranoside (pNPbetaG) and the natural
      substrate cellobiose, it showed higher specificity for pNPbetaG (kcat/Km = 6 s
      1.mM-1) than cellobiose (kcat/Km = 0.6 s-1.mM-1). AmBgl-LP showed maximum
      activity at 40  degrees C and pH 6.0 when pNPbetaG was used as the substrate.
      Glucose is a competitive inhibitor of AmBgl-LP, presenting a Ki of 14 mM. X-ray
      crystallography and Small Angle X-ray Scattering were used to determine the AmBgl
      LP three-dimensional structure and its oligomeric state. Interestingly, despite
      sharing similar active site architecture with other structurally characterized
      GH1 family members which are monomeric, AmBgl-LP forms stable dimers in solution.
      The identification of new GH1 members by metagenomics might extend our
      understanding of the molecular mechanisms and diversity of these enzymes, besides
      enabling us to survey their industrial applications.

PMID- 29454993
TI  - In vitro studies of disease-linked variants of human tRNA nucleotidyltransferase
      reveal decreased thermal stability and altered catalytic activity.
AB  - Mutations in the human TRNT1 gene encoding tRNA nucleotidyltransferase (tRNA-NT),
      an essential enzyme responsible for addition of the CCA (cytidine-cytidine
      adenosine) sequence to the 3'-termini of tRNAs, have been linked to disease
      phenotypes including congenital sideroblastic anemia with B-cell
      immunodeficiency, periodic fevers and developmental delay (SIFD) or retinitis
      pigmentosa with erythrocyte microcytosis. The effects of these disease-linked
      mutations on the structure and function of tRNA-NT have not been explored. Here
      we use biochemical and biophysical approaches to study how five SIFD-linked amino
      acid substitutions (T154I, M158V, L166S, R190I and I223T), residing in the N
      terminal head and neck domains of the enzyme, affect the structure and activity
      of human tRNA-NT in vitro. Our data suggest that the SIFD phenotype is linked to
      poor stability of the T154I and L166S variant proteins, and to a combination of
      reduced stability and altered catalytic efficiency in the M158 V, R190I and I223T
      variants.

PMID- 29454994
TI  - Epigallocatechin-3-gallate loaded PEGylated-PLGA nanoparticles: A new anti
      seizure strategy for temporal lobe epilepsy.
AB  - Temporal lobe epilepsy is the most common type of pharmacoresistant epilepsy in
      adults. Epigallocatechin-3-gallate has aroused much interest because of its
      multiple therapeutic effects, but its instability compromises the potential
      effectiveness. PEGylated-PLGA nanoparticles of Epigallocatechin-3-gallate were
      designed to protect the drug and to increase the brain delivery. Nanoparticles
      were prepared by the double emulsion method and cytotoxicity, behavioral, Fluoro
      Jade C, Iba1 and GFAP immunohistochemistry studies were carried out to determine
      their effectiveness. Nanoparticles showed an average size of 169 nm, monodisperse
      population, negative surface charge, encapsulation efficiency of 95% and
      sustained release profile. Cytotoxicity assays exhibited that these nanocarriers
      were non-toxic. Behavioral test showed that nanoparticles reduced most than free
      drug the number of epileptic episodes and their intensity. Neurotoxicity and
      immunohistochemistry studies confirmed a decrease in neuronal death and
      neuroinflammation. In conclusion, Epigallocatechin-3-gallate PEGylated-PLGA
      nanoparticles could be a suitable strategy for the treatment of temporal lobe
      epilepsy.

PMID- 29454996
TI  - Apo-10'-lycopenoic acid inhibits cancer cell migration and angiogenesis and
      induces peroxisome proliferator-activated receptor gamma.
AB  - SCOPE: We have previously shown that apo-10'-lycopenoic acid (ALA), a derivative
      of lycopene through cleavage by carotene-9',10'-oxygenase, inhibits tumor
      progression and metastasis in both liver and lung cancer animal models. The
      underlying mechanism remains unknown. We hypothesized that ALA inhibits cancer
      cell motility and angiogenesis by up-regulating peroxisome proliferator-activated
      receptor gamma (PPARgamma) which is involved in controlling angiogenesis, tumor
      progression and metastasis. METHODS AND RESULTS: ALA treatment, in dose-dependent
      manner, was effective at inhibiting migration and invasion of liver and lung
      cancer cells (HuH7 and A549) in both Transwell and wound-healing models, as well
      as suppressing actin remodeling and ruffling/lamellipodia formation in HuH7 and
      immortalized lung BEAS-2B cells. ALA treatment resulted in suppression of
      angiogenesis in both tube formation and aortic ring assays and inhibition of
      matrix metalloproteinase-2 expression and activation in both HuH7 and A549 cells.
      Additionally, ALA dose-dependently increased the mRNA expression and protein
      levels of PPARgamma in human THLE-2 liver cells. CONCLUSION: ALA inhibits cancer
      cell motility and angiogenesis and induces PPARgamma expression, which could be
      one of the potential mechanisms for ALA protecting against tumor progression.

PMID- 29454995
TI  - Role of HBx in hepatitis B virus persistence and its therapeutic implications.
AB  - Chronic hepatitis B virus infection is a significant risk factor for cirrhosis
      and hepatocellular carcinoma. The HBx protein is required for virus replication,
      but the lack of robust infection models has hindered our understanding of HBx
      functions that could be targeted for antiviral purposes. We briefly review three
      properties of HBx: its binding to DDB1 and its regulation of cell survival and
      metabolism, to illustrate how a single viral protein can have multiple effects in
      a cell. We propose that different functions of HBx are needed, depending on the
      changing hepatocyte environment encountered during a chronic virus infection, and
      that these functions might serve as novel therapeutic targets for inhibiting
      hepatitis B virus replication and the development of associated diseases.

PMID- 29454997
TI  - Regulatory responses of hepatocytes, macrophages and vascular endothelial cells
      to magnesium deficiency.
AB  - The liver is the organ that responds to nutritional disturbances including
      magnesium deficiency. The present study evaluated cellular responses to magnesium
      deficiency using model cells of the liver, namely, HepG2 cells as hepatocytes,
      RAW264.7 cells as Kupffer cells and human umbilical vein endothelial cells
      (HUVECs) as vascular endothelial cells; we examined effects of culture with
      magnesium deficient medium on cell responses in individual types of cells as well
      as interactive responses among cells. Metabolomic analyses indicated that
      magnesium deficiency differentially affected the cellular content of metabolites
      among HepG2 cells, RAW264.7 cells and HUVECs. The cellular content of the
      metabolites in HepG2 cells and HUVECs was also affected by the conditioned medium
      from RAW264.7 cells cultured with the magnesium-deficient media. The changes in
      HUVECs partly resembled those of the livers of magnesium-deficient rats
      previously described. RNA-seq analyses indicated that magnesium deficiency
      modulated the expression levels of molecules related to the ubiquitin-proteasome
      pathway and oxidative stress/antioxidant response in HepG2 cells and RAW264.7
      cells, respectively. Furthermore, when HUVECs were co-cultured with RAW264.7
      cells, lipopolysaccharide-induced expression of interleukin (IL)-1beta and IL-6
      was enhanced by magnesium deficiency, depending on the presence of RAW264.7
      cells. The present study reveals that magnesium deficiency affects cellular
      metabolism in HepG2 liver cells, RAW264.7 macrophages and HUVECs, and that the
      modulation of cellular responses to extracellular magnesium deficiency in HUVECs
      depends on the presence of RAW264.7 cells. The complex responses in individual
      cells and through cell interactions partly explain the regulatory reaction to
      magnesium deficiency in the liver.

PMID- 29454998
TI  - A cell death assay for assessing the mitochondrial targeting of proteins.
AB  - The mitochondrial proteome comprises 1000 to 1500 proteins, in addition to
      proteins for which the mitochondrial localization is uncertain. About 800
      diseases have been linked with mutations in mitochondrial proteins. We devised a
      cell survival assay for assessing the mitochondrial localization in a high
      throughput format. This protocol allows us to assess the mitochondrial
      localization of proteins and their mutants, and to identify drugs and nutrients
      that modulate the mitochondrial targeting of proteins. The assay works equally
      well for proteins directed to the outer mitochondrial membrane, inner
      mitochondrial membrane mitochondrial and mitochondrial matrix, as demonstrated by
      assessing the mitochondrial targeting of the following proteins: carnitine
      palmitoyl transferase 1 (consensus sequence and R123C mutant), acetyl-CoA
      carboxylase 2, uncoupling protein 1 and holocarboxylase synthetase. Our screen
      may be useful for linking the mitochondrial proteome with rare diseases and for
      devising drug- and nutrition-based strategies for altering the mitochondrial
      targeting of proteins.

PMID- 29455000
TI  - The impact of increased number of low-risk deliveries on maternal and neonatal
      outcomes: A retrospective cohort study in Finland in 2011-2015.
AB  - OBJECTIVES: Our aim was to demonstrate the influence of increased number of low
      risk deliveries on obstetric and neonatal outcome. STUDY DESIGN: The study
      hospital was Katiloopisto Maternity Hospital in Helsinki. Simultaneously, we
      studied all three delivery units in the Helsinki region in the population-based
      analysis. The study population was singleton hospital deliveries occurring
      between 2011 and 2012, and 2014-2015. The study hospital included 11 237 and 15
      637 births and the population-based group included 28 950 and 27 979 births. We
      compared outcome measures in different periods by calculating adjusted odds
      ratios (AOR). Main outcome measures were induced delivery, mode of delivery,
      third or fourth degree perineal tear, Apgar score at five minutes <7, umbilical
      artery pH <7.00, transfer to higher level of neonatal care, neonatal antibiotic
      treatment, respiratory support of the neonate, hospitalization of the neonate >7
      days, and perinatal death. RESULTS: In the study hospital, induction rate
      increased from 22.4% to 24.8% (AOR 1.06, 95% CI; 1.00-1.12) while in the
      population-based analysis the rate decreased from 22.2% to 21.5% (AOR 0.96, 95%
      CI; 0.92-1.00). Percentage of neonatal transfers, low Apgar scores, and severe
      perineal tears increased both in study hospital and in population-based group.
      Changes in operative delivery rate and other adverse perinatal outcomes were
      statistically insignificant. CONCLUSIONS: Increasing the volume of a delivery
      unit does not compromise maternal or neonatal outcome. Specific characteristics
      of a delivery unit affect the volume outcome association.

PMID- 29454999
TI  - Long-term treatment with green tea polyphenols modifies the gut microbiome of
      female sprague-dawley rats.
AB  - Green tea polyphenols (GTP) have been shown to exert a spectrum of health
      benefits to animals and humans. It is plausible that the beneficial effects of
      GTP are a result of its interaction with the gut microbiota. This study evaluated
      the effect of long-term treatment with GTP on the gut microbiota of experimental
      rats and the potential linkage between changes of the gut microbiota with the
      beneficial effects of GTP. Six-month-old Sprague-Dawley rats were randomly
      allocated into three dosing regimens (0, 0.5%, and 1.5% of GTP) and followed for
      6 months. At the end of month 3 or month 6, half of the animals from each group
      were sacrificed and their colon contents were collected for microbiome analysis
      using 16S ribosomal RNA and shotgun metagenomic community sequencing. GTP
      treatment significantly decreased the biodiversity and modified the microbial
      community in a dose-dependent manner; similar patterns were observed at both
      sampling times. Multiple operational taxonomic units and phylotypes were
      modified: the phylotypes Bacteroidetes and Oscillospira, previously linked to the
      lean phenotype in human and animal studies, were enriched; and
      Peptostreptococcaceae previously linked to colorectal cancer phenotype was
      depleted in GTP treated groups in a dose-dependent manner. Several microbial gene
      orthologs were modified, among which genes related to energy production and
      conversion were consistently enriched in samples from month 6 in a dose-dependent
      manner. This study showed that long-term treatment with GTP induced a dose
      dependent modification of the gut microbiome in experimental rats, which might be
      linked to beneficial effects of GTP.

PMID- 29455001
TI  - Evolution and molecular mechanism of PitAs in iron transport of Streptococcus
      species.
AB  - Iron is an essential element for almost all bacteria. The iron ATP-binding
      cassette (ABC) transporters located on the cell membrane affects bacterial
      virulence and infection. Although a variety of Fe3+-transporters have been found
      in bacteria, their evolutionary processes are rarely studied. Pneumococcal iron
      ABC transporter (PitA), a highly conserved Fe3+-transporter in most pathogenic
      bacteria, influences the capsule formation and virulence of bacteria. However,
      multiple sequence alignment revealed that PitA is expressed in four different
      variants in bacteria, and the structural complexity of these variants increases
      progressively. To more efficiently import Fe3+ ions into bacterial cells,
      bacteria have evolved a fused PitA from two separately expressed PitA-1
      (SPD_0227) and PitA-2 (SPD_0226) proteins. Further biochemical characterization
      indicated that both PitA-1 and PitA-2 have weaker Fe3+-binding ability than their
      protein complex. More importantly, Glutathione S-Transferase (GST) pull-down and
      isothermal titration calorimetry (ITC) detection showed that PitA-1 and PitA-2
      interact with each other via Tyr111-Leu37, Asn112-Gln38, Asn103-Leu33, and Asn103
      Thr34. Further molecular dynamics (MD) simulations demonstrated that this
      interaction in full-length PitA is stronger than that in the two individual
      proteins. Deletion of PitA family genes could lead to decrease in the ability of
      iron acquisition and of adhesion and invasion of S. pneumoniae. Our study
      revealed the evolving state and molecular mechanism of Fe3+-transporter PitAs in
      bacteria and provided important information for understanding the iron
      transportation mechanism in bacteria and designing new antibacterial drugs.

PMID- 29455002
TI  - The possible neuroprotective effect of ellagic acid on sodium arsenate-induced
      neurotoxicity in rats.
AB  - OBJECTIVE: Arsenic is a well-known environmental contaminant, causing toxicity in
      different organs. The aim of this study was to investigate the possible
      neuroprotective effect of ellagic acid (EA) on arsenic-induced neurotoxicity in
      rats. DESIGN: Animals were divided into five groups. The first group received
      normal saline (2 mL/kg) for 21 days as control group. Group 2 was orally treated
      with sodium arsenite (SA, 10 mg/kg) for 21 days. Groups 3 and 4 were orally
      treated with SA (10 mg/kg) for 7 days prior to EA (10 and 30 mg/kg respectively)
      treatment and continued up to 21 days simultaneously with SA administration.
      Group 5 was orally treated with EA (30 mg/kg) for 14 days. Passive avoidance test
      and rotarod test were done to evaluate the behavioral changes following SA and/or
      EA treatment. Different biochemical, histological and molecular biomarkers were
      assessed in the brain tissue. RESULTS: Our data showed that SA significantly
      elevated brain tissue arsenic levels and malondialdehyde, nitric oxide, protein
      carbonylation, tumor necrosis factor-alpha, and interlukein-1beta production. A
      decrease in the total antioxidant capacity, reduced glutathione content and
      glutathione peroxidase activity occurred in the brain of rats exposed to SA. SA
      treated rats showed a significant impairment in long-term-memory, motor
      coordination and equilibrium. These results were supported by histopathological
      observations of the brain. Results revealed that administration of EA (30 mg/kg)
      reversed all neural markers alternation and ameliorated behavioral and
      histopathological changes induced by SA. CONCLUSION: EA can effectively protect
      brain tissue against SA-induced neurotoxicity via its antioxidant and anti
      inflammatory effects.

PMID- 29455003
TI  - Combinatorial strategy of epigenetic and hormonal therapies: A novel promising
      approach for treating advanced prostate cancer.
AB  - AIMS: Estrogens act as key factors in prostate biology, cellular proliferation
      and differentiation as well as cancer development and progression. The expression
      of estrogen receptor (ER)-beta appears to be lost during prostate cancer
      progression through hypermethylation mechanism. Epigenetic drugs such as 5-aza-2'
      deoxycytidine (5-AZAC) and Trichostatin A (TSA) showed efficacy in restoring
      ERbeta expression in prostate cancer cells. This study was designed to explore
      the potential anti-carcinogenic effects resulting from re-expressing ERbeta1
      using 5-AZAC and/or TSA, followed by its stimulation with Diarylpropionitrile
      (DPN), a selective ERbeta1 agonist, in prostate cancer cell line PC-3. MAIN
      METHODS: Cells were treated with 5-AZAC, TSA, DPN and their combination.
      Subsequently, they were subjected to proliferation assays, determinations of
      ERbeta1 expression, protein levels of active caspase-3, cyclin D1, beta-catenin
      and VEGF. KEY FINDINGS: Treatment with these drugs exhibited an increase in
      ERbeta1 expression to different extents as well as active caspase-3 levels.
      Meanwhile, a significant reduction in cyclin D1, VEGF and beta-catenin levels was
      achieved as compared to the vehicle control group (p < 0.05). Interestingly, the
      triple combination regimen led to the most prominent anti-tumor responses in
      terms of increased apoptosis, reduced proliferation as well as angiogenesis.
      SIGNIFICANCE: The results support the notion that ERbeta1 acts as a tumor
      suppressor protein and suggest that sequential ERbeta1 expression and activation
      can offer significant anti-tumor responses. The study highlights that the
      strategy of merging epigenetic and hormonal therapies may be beneficial in
      treating advanced prostate cancer.

PMID- 29455004
TI  - Role of rho-kinase (ROCK) in tonic but not phasic contraction in the frog stomach
      smooth muscle.
AB  - AIMS: Rho/Rho-kinase (ROCK) signaling has extensively been shown to take part in
      mammalian smooth muscle contractions in response to diverse agents yet its role
      in the contraction of amphibian smooth muscle has not been investigated.
      Therefore, we aimed to explore any role of this pathway in the contractions of
      frog stomach smooth. MAIN METHODS: The strips were prepared and suspended in
      organ baths filled with Ringer solution. Changes in the circular strips of the
      frog stomach muscle length were recorded isotonically with a force transducer in
      organ baths. KEY FINDINGS: Carbachol (CCh) exerted both phasic and tonic
      contractions. In contrast, atropin abolished all types of contractions by CCh.
      The phasic contractions were suppressed by a Ca2+ channel blocker, nifedipine but
      not by the ROCK inhibitor, Y-27632. However, the tonic contractions were markedly
      attenuated by Y-27632. Selective M1 receptor blocker, pirenzepin, selective M3
      receptor blocker and DAMP had no effects on CCh-elicited contractions. On the
      other hand, selective M2 receptor blocker, AF-DX suppressed all types of
      contractile activity by CCh. SIGNIFICANCE: These data suggest that M2 receptor
      activation could mainly mediate CCh-induced phasic and tonic contractions, and
      ROCK seems to be involved in the CCh-induced tonic but not phasic contractions of
      the frog stomach smooth muscle.

PMID- 29455006
TI  - Analysis of cardiac stem cell self-renewal dynamics in serum-free medium by
      single cell lineage tracking.
AB  - Cardiac colony forming unit-fibroblasts (cCFU-F) are a population of stromal
      cells residing within the SCA1+/PDGFRalpha+/CD31- fraction of adult mouse hearts,
      and which have functional characteristics akin to bone marrow mesenchymal stem
      cells. We hypothesise that they participate in cardiac homeostasis and repair
      through their actions as lineage progenitors and paracrine signaling hubs.
      However, cCFU-F are rare and there are no specific markers for these cells,
      making them challenging to study. cCFU can self-renew in vitro, although the
      common use of serum has made it difficult to identify cytokines that maintain
      lineage identity and self-renewal ability. Cell heterogeneity is an additional
      confounder as cCFU-F cultures are metastable. Here, we address these limitations
      by identifying serum-free medium (SFM) for growth, and by using cCFU-F isolated
      from PdgfraGFP/+ mice to record fate outcomes, morphology and PDGFRalpha
      expression for hundreds of single cells over time. We show that SFM supplemented
      with basic fibroblast growth factor, transforming growth factor-beta and platelet
      derived growth factor, enhanced cCFU-F colony formation and long-term self
      renewal, while maintaining cCFU-F potency. cCFU-F cultured in SFM maintained a
      higher proportion of PDGFRalpha+ cells, a marker of self-renewing cCFU-F, by
      increasing Pdgfra-GFP+ divisions and reducing the probability of spontaneous
      myofibroblast differentiation.

PMID- 29455005
TI  - Could curcumin protect the dendritic trees of the CA1 neurons from shortening and
      shedding induced by chronic sleep restriction in rats?
AB  - BACKGROUND AND OBJECTIVE: This study evaluated the effect of chronic sleep
      restriction (CSR) with or without curcumin (CUR) treatment on dendritic lengths
      and spines of the CA1 hippocampus using the virtual space-ball method. MATERIALS
      AND METHODS: Male rats were randomly submitted to nine groups, including
      distilled water, CUR (100 mg/kg/day), olive oil, CSR plus distilled water, CSR
      plus CUR, CSR plus olive oil, grid-floor plus distilled water, grid-floor plus
      CUR, and grid-floor plus olive oil groups. Sleep deficiency was imposed using the
      multi-platform box containing water for 18 h/day. In 21 days, animal's brains
      were prepared for stereological studies. RESULTS: The mean dendrite length in CA1
      neurons was reduced by 39% (p < 0.05) while the density of stubby, thin, and
      mushroom spines reduced by 38%, 33% and 32%, respectively (p < 0.01), in the CSR
      + distilled water group compared to the distilled water group. Yet, CUR treatment
      in CSR-rats was found to protect the declined dendritic length as well as loss of
      stubby and mushroom but not thin spines. CONCLUSION: The estimated dendritic
      length using the virtual space-ball method revealed that chronic sleep
      restriction for 18 h/day over 21 days could induce shortening and shedding of the
      CA1 dendritic trees which could notably be protected by CUR.

PMID- 29455007
TI  - Embryoid body arrays: Parallel cryosectioning of spheroid/embryoid body samples
      for medium through-put analysis.
AB  - Three dimensional (3D) culture of mammalian cells is emerging as a powerful new
      tool to understand organogenesis as well as serve as models for diseases with
      implications for therapeutic evaluation. 3D cultures are referred to variously as
      spheroid, organoids or embryoid bodies. While many methods exist for large scale
      production of embryoid bodies or other spheroid cell aggregates, either at
      controlled sizes using microwell/micropatterned plates or uncontrolled sizes in
      suspension dishes, very few protocols exist for medium throughput analysis of
      differentiation at the histological level. We have developed a method which
      allows for parallel processing, sectioning and analysis of multiple 3D samples
      (e.g. fixed at different time points, treated with different drugs/growth
      factors, generated from different cell lines etc.) by double-embedding blocks in
      a larger array format. Our protocol has few barriers for use and requires only
      materials commonly found in any lab currently using embedding materials for
      cryosectioning. Sectioning in parallel allows histological techniques (such as
      histochemistry, immunostaining or in situ hybridisation) to be performed
      simultaneously on many samples on a single slide. This reduces slide to slide
      variation as well as requiring less reagents, fewer consumables with lower time
      and labour requirements when compared to individually embedded samples.

PMID- 29455008
TI  - Quantitative estimation of mercury intake by toxicokinetic modelling based on
      total mercury levels in humans.
AB  - Mercury is a toxic metal that can be disseminated into the environment from both
      natural and anthropogenic sources. Human exposure to the metal stems mainly from
      food, and more particularly from the consumption of fish and other seafoods.
      Examining dietary exposure and measuring mercury levels in body tissues are two
      ways of estimating exposure to mercury. In this study, we utilized a modelling
      system consisting of three linear toxicokinetic models for describing the fate of
      methyl mercury, inorganic mercury, and metallic mercury in the body, in order to
      estimate daily intake of mercury as measured through total mercury concentrations
      in the blood. We then compared the results stemming from our modelling system to
      those of the detailed semi-quantitative food frequency questionnaire (FFQ) of the
      Norwegian Fish and Game (NFG) Study, a project that focused on dietary mercury
      exposure. The results indicate that toxicokinetic modelling based on blood levels
      gave higher daily intake values of mercury compared to those of the FFQ.
      Furthermore, the former had a wider range of estimates than the latter. The
      properties of the toxicokinetic model or limitations in the dietary exposure
      assessment could be posited as reasons for the differences between the respective
      methods. Moreover, the results may have been influenced by sources of mercury
      exposure that cannot be described as dietary, such as amalgam fillings.

PMID- 29455009
TI  - Protecting an adult identity: A grounded theory of supportive care for young
      adults recently diagnosed with cancer.
AB  - BACKGROUND: For adolescents and young adults living in high-income countries
      cancer remains the most common disease-related death. Increasing survival rates
      and projected longevity are positive outcomes, although long-term consequences of
      cancer and/or its treatment will likely increase the global burden of cancer. In
      low and middle-income countries the impact and needs of young adults with cancer
      are largely unknown and require further attention. However, universal studies
      have revealed that cancer-related needs for this group are multifactorial,
      complex and largely unmet. In response to these findings, the body of work on
      supportive care for young adults with cancer is growing. Yet, there is no
      published research in the context of the United Kingdom, regarding the role young
      adults play in managing their supportive cancer care needs. OBJECTIVE: To explore
      the experience, purpose and meaning of supportive cancer care to young adults
      recently diagnosed with cancer. DESIGN, SETTING AND PARTICIPANTS: Using
      constructivist grounded theory, data were collected in one to one interviews with
      eleven young adults (seven women and four men aged 19-24 years) being treated for
      cancer in two English hospitals. Data were analyzed using open and focused
      coding, constant comparison, theoretical coding and memoing, and this enabled
      construction of a subjective theory. RESULTS: Young adults in this study
      interpreted cancer as an interruption to the events, experiences and tasks
      forming the biographical work of their adult identity. Data analysis led to the
      construction of the theory, 'protecting an adult identity: self in relation to a
      diagnosis of cancer in young adulthood'. This theory arose from three categories:
      fragility of self, maintaining self in an altered reality and mobilizing external
      resources. Young adults faced the loss of their early adult identity.
      Interpreting cancer as a temporary interruption, they sought to re-establish
      their identity by directly and indirectly managing their supportive care needs.
      CONCLUSIONS: These findings contribute to the understanding of young adults'
      desired purpose of supportive cancer care. There are also implications for how
      health and social care professionals provide supportive care interventions to
      meet the needs of this population.

PMID- 29455010
TI  - Long-Term Outcomes of Thoracic Endovascular Aortic Repair Focused on Bird Beak
      and Oversizing in Blunt Traumatic Thoracic Aortic Injury.
AB  - BACKGROUND: The acute aortic arch angle and narrow aortic diameter in young
      patients may lead to bird-beak configuration and excessive oversizing of the
      stent graft in thoracic endovascular aortic repair (TEVAR) for blunt traumatic
      thoracic aortic injury (BTTAI). Little is known about the association of these
      factors and complications in long-term follow-up. We evaluated the long-term
      outcomes in terms of complications, reinterventions, and survival, focusing on
      the effects of bird-beak configuration and oversizing. METHODS: This prospective
      cohort study included patients who underwent TEVAR for BTTAI in our department
      between October 1999 and January 2015. The main outcomes were migration,
      collapse, intragraft mural thrombus, reintervention, and survival and their
      association with oversizing and bird-beak configuration. RESULTS: Thirty-four
      patients were included. Median age was 36 years, and 21% were women. Mean graft
      oversizing was 19% (range: 8-27%) at the proximal end and 27% (range:, -20% to
      50%) at the distal end. Mean follow-up was 98 months (12-198 months). Seven
      patients presented intragraft mural thrombus, one of whom developed an occlusive
      parietal thrombosis 1 year after the procedure. Four patients (9%) required
      reintervention: postoperative revascularization of the left subclavian artery in
      2 cases and aortic reinterventions in 2 others. No migration or mortality was
      seen during follow-up. Bird-beak configuration was seen in 65%: the mean
      protrusion extension was 16 mm (standard deviation [SD]: 7.4 mm) and the mean
      angle was 51 degrees  (SD: 16 degrees ). The association between the
      complications and bird beak was not statistically significant. Patients with
      complications had significantly higher proximal end oversizing (23%) than the
      group with no complications (17%) (P = 0.0007). CONCLUSIONS: TEVAR for BTTAI
      shows good results in the long-term follow-up. Complications in our series seemed
      related to proximal end oversizing. Thoracic stent grafts with a smaller diameter
      should be available in all trauma centers to avoid excessive oversizing.

PMID- 29455011
TI  - Hybrid Retrograde Celiac Artery Stenting for Acute Mesenteric Ischemia after
      Gastric Surgery.
AB  - BACKGROUND: Celiac artery (CA) occlusions/stenosis is infrequently associated
      with liver ischemia due to its unique vascularization, where portal vein provides
      about 75% of liver's perfusion. Collateral flow from gastroduodenal artery also
      provides, in most cases, enough blood supply to prevent ischemic hepatitis. In
      cases where these collateral pathways are compromised, severe liver ischemia can
      occur. METHODS: We present a case of acute mesenteric ischemia following gastric
      surgery that was treated with a hybrid retrograde CA stenting. RESULTS: We report
      a case of a 72-year-old male, who underwent gastric surgery for gastric cancer.
      On fourth postoperative day, he presented with acute abdomen, and on laparotomy,
      a partial duodenal suture dehiscence was found and suture closed. Owing to
      worsening of patient's clinical condition, with associated ischemic hepatitis, 2
      days later, a computed tomography angiography was performed that showed a
      superior mesenteric artery (SMA) occlusion at its origin with an associated,
      severe, ostial stenosis of the CA. On laparotomy, irreversible visceral ischemia
      was found, which led to total colectomy, resection of 50 cms of small bowel, and
      splenectomy. Liver ischemia was also confirmed. Femoral access was used to try to
      cannulate the CA and cross its stenosis, without success. Taking advantage of the
      open abdomen, we then opted to place a 5F sheath in the splenic artery stump.
      From this retrograde approach, stenosis traversal was easy, and the CA was
      ballooned and stented with reperfusion of almost all the liver. Despite these
      efforts, patient died because of multiorganic failure, 8 days later. CONCLUSIONS:
      Ischemic hepatitis is a rare but serious complication of CA/SMA occlusive
      disease. Its occurrence is at increased risk after surgeries, where collateral
      flow is compromised. The endovascular treatment is currently the preferred
      approach to treat visceral arteries occlusive disease; however, antegrade CA
      cannulation can be tricky, and in an open abdomen scenario, retrograde approach
      from the splenic artery can be an additional resource. This case demonstrates the
      flexibility of endovascular techniques and that they can provide useful solutions
      even during open surgery.

PMID- 29455012
TI  - Deep Venous Thrombosis in a Patient with Duplication of the Common Iliac Vein.
AB  - A congenital abnormality of the inferior vena cava is said to be an anatomical
      risk factor for venous thromboembolism. In this report, we present a case of a
      patient with a left duplicated common iliac vein who developed a venous
      thromboembolism following total abdominal hysterectomy and bilateral salpingo
      oophorectomy. Only 2 items were risk factors for thromboembolism: age of >=40
      years and open surgery duration of >=30 min; no congenital abnormalities of the
      inferior vena cava or thrombotic factors were observed. Thus, it was suspected
      that the duplicated common iliac vein could have caused the venous
      thromboembolism.

PMID- 29455013
TI  - Laser Recanalization of Central Venous Occlusion to Salvage a Threatened
      Arteriovenous Fistula.
AB  - Central venous occlusion is conventionally managed with balloon angioplasty,
      stent extension, or sharp recanalization. Here, we describe recanalization of a
      chronically occluded innominate vein using excimer laser after conventional
      techniques were unsuccessful. Patient clinical improvement and fistula patency
      have been sustained 2 years postintervention. This technique may provide new
      hemodialysis access options for patients who would not otherwise be candidates
      for hemodialysis access on the ipsilateral side of a central venous occlusion.

PMID- 29455014
TI  - Cilostazol Improves Wound Healing in Patients Undergoing Open Bypass for Ischemic
      Tissue Loss: A Propensity Score Matching Analysis.
AB  - BACKGROUND: Few reports have described the effects of medication on the wound
      healing of ischemic ulcers after revascularization. This study was conducted to
      investigate the effects of cilostazol on wound healing in patients who underwent
      infrainguinal bypass for ischemic tissue loss. METHODS: Two hundred sixty-three
      limbs undergoing de novo infrainguinal bypass for tissue loss from January 2004
      to December 2015 were divided into 2 groups based on whether or not cilostazol
      was administered after surgery. The end point was wound healing. The 1-year
      outcomes of the groups were analyzed using the Kaplan-Meier method, and a
      propensity score matching analysis was performed to examine the effects of
      cilostazol on wound healing. In addition, the significant predictors were
      determined using a Cox proportional hazards regression analysis. RESULTS: Sixty
      one and 202 limbs were included in the cilostazol and non-cilostazol group,
      respectively. The cilostazol group showed superior wound healing to the non
      cilostazol group (cilostazol versus non-cilostazol, 1-year wound healing rate:
      92% vs. 81%; median wound healing time: 45 vs. 78 days, P = 0.002). The results
      of the cilostazol group remained superior after a propensity score matching
      (cilostazol versus non-cilostazol, 1-year wound healing rate: 95% vs. 83%; median
      wound healing time: 45.5 vs. 57 days, P = 0.048). A Cox proportional hazards
      regression analysis indicated that foot infection, Rutherford classification,
      diabetes mellitus, coronary artery disease, angiosome, the administration of
      cilostazol, and graft patency were significant factors that influenced wound
      healing. CONCLUSIONS: The postoperative use of cilostazol help to promote wound
      healing after open surgery.

PMID- 29455015
TI  - Symptomatic Type B Intramural Aortic Hematoma as a Complication of Retrograde
      Right Common Iliac Artery Dissection.
AB  - PURPOSE: To report the endovascular treatment of a spontaneous iliac artery
      dissection (IAD) involving iliac bifurcation, complicated by a type B intramural
      aortic hematoma (IMH). CASE REPORT: A 38-year-old female patient came to our
      institution referring an acute ascending back pain. The angio computed tomography
      scan showed the presence of a retrograde right IAD with entry tear at the iliac
      bifurcation and a concomitant aortic IMH. After hypogastric embolization with a
      vascular plug, self-expanding stent graft was placed to cover the iliac entry
      tear. At 12 months, the patient was asymptomatic and the angio computed
      tomography scan showed the patency of the iliac graft without IMH. CONCLUSIONS:
      Endovascular treatment of spontaneous IAD is a safe and effective option in
      symptomatic patient complicated with type B IMH.

PMID- 29455016
TI  - Descending Aorta Rupture after Transcatheter Aortic Valve Embolization.
AB  - BACKGROUND: To report a case of rupture of the descending aorta after aortic
      migration during transcatheter aortic valve replacement (TAVR). METHODS: An 85
      year-old man with a severe and symptomatic aortic stenosis underwent elective
      TAVR, which complicated with embolization into the ascending aorta. While
      repositioning into the descending aorta, the procedure complicated with aortic
      rupture. RESULTS: The patient required urgent thoracic intravalve stent-graft
      implantation (thoracic endovascular aortic repair [TEVAR]). Reintervention with
      other stent graft was required 2 days after initial procedure as proximal rupture
      was again diagnosed. Patient was discharged 50 days later because of other
      medical complications. He remains stable at 1 year of follow-up. CONCLUSIONS:
      TEVAR is a valid and safe option in the treatment of iatrogenic acute aortic
      rupture due to TAVR.

PMID- 29455017
TI  - Thrombectomy Devices in the Treatment of Acute Mesenteric Ischemia: Initial
      Single-Center Experience.
AB  - BACKGROUND: To report our preliminary experience with endovascular
      revascularization of patients with acute mesenteric ischemia (AMI), using
      thrombectomy devices. METHODS: It is a retrospective analysis of patients
      admitted to our hospital due to AMI and who were subjected to concomitant or
      exclusive endovascular treatment, from January 2011 to January 2016. Patients
      were admitted at the emergency department, underwent imaging investigation, and
      were referred to the endovascular specialist. Endovascular treatment was
      performed through left brachial artery access and selective catheterization and
      thrombectomy with a 6F Rotarex Debulking Device (Straub Medical, Wangs,
      Switzerland). Laparotomy was performed based on clinical and radiologic sings and
      at the discretion of the surgeon. Demographic, clinical/periprocedural,
      postoperative, complication, and adjunct intervention data were reviewed.
      Technical success was defined as recanalization of the Riolan's arcade on
      angiographic control. RESULTS: Twenty patients (mean age: 69.8 +/- 11.3 years)
      underwent endovascular revascularization for AMI using thrombectomy devices,
      during the period of the study. Abdominal pain was the most common complain on
      admission (65%), with ileus (35%), sepsis (25%), and myocardial infarction as the
      main clinical referral presentation at admission. Fifteen patients (75%) had
      suggestive computer tomography (CT) signs of AMI on admission. Endovascular
      revascularization was successfully performed in all patients through the left
      brachial artery with a mean procedural time of 28 +/- 17 min. Superior mesenteric
      artery (SMA) was the main vessel involved in 75% on a solely basis. The majority
      of the SMA occlusions were in the periosteal (30%) and proximal to middle colic
      artery offspring (35%). Primary use of thrombectomy devices was performed in all
      patients, associated with balloon angioplasty (7/20; 50%), stent deployment
      (5/20; 25%), intraoperative selective thrombolysis (4/20; 20%) and catheter
      assisted aspiration in 10% (2/20) of patients. Average time between admission and
      computed tomography angiography was 1.5 +/- 0.5 hr, between admission and
      angiographic procedure was 2.5 +/- 1 hr, and between admission and surgery was 9
      +/- 5 hr. Following recanalization, 14 patients (70%) underwent open surgery.
      Laparotomy with intestinal resection (enterectomy, colectomy) and transit
      deviation was the most common procedure. Complications directly related to the
      endovascular procedure occurred in 2 patients, represented by self-limited small
      perforations. Overall 30-day mortality was 40% (n = 8). During the period of this
      study, no patient died as a result of complications related to the use of
      rotational thrombectomy. CONCLUSIONS: Endovascular treatment of the AMI with the
      use of thrombectomy devices proved to be technically feasible and reasonably fast
      procedure. Early diagnosis and adequate treatment remains the cornerstone of the
      treatment. Early surgical evaluation and close integration between surgical and
      endovascular specialists are crucial to faster treatment and consequently lower
      extensive surgical resections and mortality. Further studies are necessary on
      this field to confirm these findings.

PMID- 29455018
TI  - Acute Massive Pulmonary Thromboembolism Treated by Selective Catheter-Directed
      Thrombolysis.
AB  - BACKGROUND: To evaluate the safety and efficacy of selective catheter-directed
      thrombolysis (SCDT) in treating acute massive pulmonary thromboembolism (AMPTE).
      METHODS: Twenty-six AMPTE patients were enrolled between March 2010 and March
      2013. A Uni*Fuse infusion system was inserted into the main pulmonary artery
      thrombus. The thrombolytic regimen included an intraoperative bolus injection of
      250,000 IU urokinase, followed by continuous thrombolytic infusion of 5,000 IU/kg
      per (every) 24 hr urokinase for 72 hr postoperatively. Clinical symptoms, shock
      index (SI), systolic pulmonary artery pressure (sPAP), peripheral arterial
      partial pressure of oxygen (PaO2), and Miller index (MI) were assessed before and
      after treatment. RESULTS: The patients included 16 men and 10 women (49.9 +/-
      18.8 years old; time to onset of 50.2 +/- 28.5 hr). After thrombolysis, dyspnea
      and cough were relieved to varying degrees; chest pain, hemoptysis, and syncope
      disappeared. Importantly, a clinical success rate of 100% was achieved. All
      objective indices were improved: SI decreased from 1.74 +/- 0.38 before operation
      to 0.71 +/- 0.09 postoperatively (P = 0.00); PaO2 increased from 52.78 +/- 6.92
      mm Hg to 85.98 +/- 5.91 mm Hg (P = 0.00); sPAP was reduced from 65.19 +/- 8.22 mm
      Hg to 34.42 +/- 4.05 mm Hg (P = 0.00); MI dropped from 0.69 +/- 0.09 to 0.33 +/-
      0.06 (P = 0.00). Mean total urokinase amounts were 1,298,000 IU for each patient.
      Postoperative complications included 2 cases of puncture-site hematoma (cured by
      pressure bandage) and 1 case of gastrointestinal hemorrhage (healed by
      conservative treatment without blood transfusion). CONCLUSIONS: SCDT may be
      considered a safe and efficacious treatment for AMPTE.

PMID- 29455019
TI  - Ocular Myasthenia Induced by Rivaroxaban in Patient with Deep Vein Thrombosis.
AB  - The non-vitamin K antagonist oral anticoagulant rivaroxaban is indicated in
      prevention and treatment of venous thromboembolism (VTE). A 60-year-old male
      patient complained of bilateral ptosis after administration of rivaroxaban for
      deep vein thrombosis (DVT). Myasthenia gravis (MG) was confirmed by positive
      serum antiacetylcholine receptor antibody test. No mediastinal thymoma was found.
      The ocular myasthenia reversed after discontinuing rivaroxaban treatment.
      Nevertheless, ptosis recurred and chronic oral pyridostigmine bromide treatment
      was necessary. The mechanism of MG development by rivaroxaban therapy is not
      completely understood. The development of rivaroxaban-induced autoimmune disease
      could be based on cross-reactivity between antibodies against rivaroxaban-derived
      antigens or by T-cell activation. To our knowledge, this report of ocular
      myasthenia by rivaroxaban administration is the first in the literature. Despite
      the benefits of rivaroxaban, it is important to recognize unexpected immune
      related adverse events.

PMID- 29455020
TI  - Bayesian networks of age estimation and classification based on dental evidence:
      A study on the third molar mineralization.
AB  - Not only does the Bayesian approach offer a rational and logical environment for
      evidence evaluation in a forensic framework, but it also allows scientists to
      coherently deal with uncertainty related to a collection of multiple items of
      evidence, due to its flexible nature. Such flexibility might come at the expense
      of elevated computational complexity, which can be handled by using specific
      probabilistic graphical tools, namely Bayesian networks. In the current work,
      such probabilistic tools are used for evaluating dental evidence related to the
      development of third molars. A set of relevant properties characterizing the
      graphical models are discussed and Bayesian networks are implemented to deal with
      the inferential process laying beyond the estimation procedure, as well as to
      provide age estimates. Such properties include operationality, flexibility,
      coherence, transparence and sensitivity. A data sample composed of Italian
      subjects was employed for the analysis; results were in agreement with previous
      studies in terms of point estimate and age classification. The influence of the
      prior probability elicitation in terms of Bayesian estimate and classifies was
      also analyzed. Findings also supported the opportunity to take into consideration
      multiple teeth in the evaluative procedure, since it can be shown this results in
      an increased robustness towards the prior probability elicitation process, as
      well as in more favorable outcomes from a forensic perspective.

PMID- 29455022
TI  - Adaptive pathway development for Fabry disease: a clinical approach.
AB  - Fabry disease (FD) is a rare X-chromosome-linked lysosomal storage disorder.
      Although initial expectations of enzyme replacement therapy (ERT) were high, it
      is now clear that real-world effectiveness is disappointing and evidence
      gathering has been inadequate. In retrospect, development of ERT for FD had
      several shortcomings. Little convincing evidence on the effectiveness existed at
      time of authorization. Also, post-marketing evaluation failed to generate
      sufficient and relevant data for adequate evaluation on effectiveness. Adaptive
      pathways might have benefitted ERT development by: (i) involving healthcare
      professionals, patients, health technology assessment bodies and payers in the
      development process; (ii) iterative development, starting with initial
      authorization in classical males; (iii) a clear real-world data collection plan;
      (iv) an independent disease registry; and (v) prescription control.

PMID- 29455021
TI  - Effect of dopamine receptor D4 (DRD4) haplotypes on general psychopathology in
      patients with eating disorders.
AB  - Among the many candidate genes analyzed in eating disorder (ED) patients, those
      involved in dopaminergic functions may be of special relevance, as dopamine is
      known to play a significant role in feeding behavior, the distortion of body
      image, hyperactivity and reward and reinforcement processes. We aimed to
      determine the effect of functional polymorphisms and haplotypes in the Dopamine
      Receptor D4 (DRD4) gene on general psychopathological symptoms in ED patients.
      Two-hundred-and-seventy-three ED patients [199 with Anorexia Nervosa (AN) and 74
      with Bulimia Nervosa (BN)] completed the SCL-90R inventory and were genotyped for
      four functional, clinically relevant DRD4 polymorphisms: three variants in the
      promoter region [120-bp tandem repeat (TR, long vs. short allele), C-616G and C
      521 T] and a variable number of tandem repeats (VNTR) in exon 3 (7R vs. non-7R
      allele). After correcting for multiple testing, none of the assayed polymorphisms
      were individually associated with SCL-90R results. Four DRD4 haplotypes (*1-*4)
      were detected in the patients with a frequency > 0.1. In the BN group, haplotype
      *2 (non7R-TR long-C-C) was associated with higher scores in the three global SCL
      90R indices (GSI, PSDI and PST) after Bonferroni correction (p <= 0.01 in all
      instances). Furthermore, carriers of this haplotype displayed higher scores
      (worst symptomatology) in Somatization, Obsessive-Compulsive, Anxiety, Phobic
      anxiety, Paranoid ideation and the test additional items (p-values for the
      differences between carriers vs. non-carriers ranging from 0.0001 to 0.0110).
      Certain combinations of DRD4 variants may contribute to psychopathological
      features in BN patients.

PMID- 29455023
TI  - An innovative paradigm of methods in microRNAs detection: highlighting DNAzymes,
      the illuminators.
AB  - miRNAs are short regulatory sequences that monitor gene expression at post
      transcriptional level. miRNAs play outstanding roles in cellular processes and
      their altered expression or aberrant function has been reported in diseases such
      as cancer. Furthermore, some of them serve as biomarkers for prognosis,
      diagnosis, and prediction of drug effectiveness as well as probable utility in
      the field of personalized medicine. As a result, proper and sensitive detection
      of miRNAs is a crucial matter. Traditional approaches including Northern
      blotting, Microarray, and Quantitative reverse transcription polymerase chain
      reaction have been extensively employed by means of miRNA detection for decades.
      However, these methods lack sufficient sensitivity, specificity and are labor
      intensive. In the recent years, DNAzyme-based assays have become strikingly
      attractive. The principal element in these techniques is a G-rich sequence,
      called the G-quadruplex, which turns into a DNAzyme with catalytic activity by
      addition of hemin, and subsequently allows simple and rapid detection of the
      target. In this review, different methods of miRNA detection, along with related
      advantages and disadvantages are discussed, with a special focus on DNAzymes and
      DNAzyme-derived methods.

PMID- 29455024
TI  - All-carbon suspended nanowire sensors as a rapid highly-sensitive label-free
      chemiresistive biosensing platform.
AB  - Nanowire sensors offer great potential as highly sensitive electrochemical and
      electronic biosensors because of their small size, high aspect ratios, and
      electronic properties. Nevertheless, the available methods to fabricate carbon
      nanowires in a controlled manner remain limited to expensive techniques. This
      paper presents a simple fabrication technique for sub-100 nm suspended carbon
      nanowire sensors by integrating electrospinning and photolithography techniques.
      Carbon Microelectromechanical Systems (C-MEMS) fabrication techniques allow
      fabrication of high aspect ratio carbon structures by patterning photoresist
      polymers into desired shapes and subsequent carbonization of resultant structures
      by pyrolysis. In our sensor platform, suspended nanowires were deposited by
      electrospinning while photolithography was used to fabricate support structures.
      We have achieved suspended carbon nanowires with sub-100 nm diameters in this
      study. The sensor platform was then integrated with a microfluidic chip to form a
      lab-on-chip device for label-free chemiresistive biosensing. We have investigated
      this nanoelectronics label-free biosensor's performance towards bacterial sensing
      by functionalization with Salmonella-specific aptamer probes. The device was
      tested with varying concentrations of Salmonella Typhimurium to evaluate
      sensitivity and various other bacteria to investigate specificity. The results
      showed that the sensor is highly specific and sensitive in detection of
      Salmonella with a detection limit of 10 CFU mL-1. Moreover, this proposed
      chemiresistive assay has a reduced turnaround time of 5 min and sample volume
      requirement of 5 uL which are much less than reported in the literature.

PMID- 29455025
TI  - Dual nanoenzyme modified microelectrode based on carbon fiber coated with AuPd
      alloy nanoparticles decorated graphene quantum dots assembly for electrochemical
      detection in clinic cancer samples.
AB  - The development of high-efficient technologies for cancer biomarkers detection
      has attracted tremendous research effort for its great clinic significance. In
      this work, we designed a new type of flexible and robust nanohybrid
      microelectrode by modifying carbon fiber with dual nanoenzyme, i.e., AuPd alloy
      nanoparticles (AuPd-ANPs) decorated graphene quantum dots (GQDs) assembly, and
      explored its practical application in electrochemical sensing system for
      sensitive detection of cancer biomarker hydrogen peroxide (H2O2) in human breast
      cancer cells and tissue. For the preparation of dual nanoenzyme modified
      microelectrode, ionic liquid was used as the electrolyte for the effective
      electrodeposition of GQDs on carbon fiber substrate to form a close-packed
      assembly under a very negative potential, then the highly dense AuPd-ANPs were
      uniformly decorated on GQDs assembly by electrodeposition. In virtue of the
      structural merits and synergistic contribution of dual nanoenzyme in enhancing
      the electrocatalytic activity to H2O2, the resultant nanohybrid microelectrode
      exhibited good sensing performances for electrochemical detection of H2O2,
      including a high sensitivity of 371 MUA cm-2 mM-1, a wide linear range from 1.0
      MUM to 18.44 mM, a low detection limit of 500 nM (a signal-to-noise ratio of
      3:1), as well as good selectivity and biocompatibility, which could be used for
      real-time tracking H2O2 released from different types of human breast cells and
      in situ sensitive detection of H2O2 in clinical breast cancer tissue.

PMID- 29455026
TI  - An approach for cell viability online detection based on the characteristics of
      lensfree cell diffraction fingerprint.
AB  - To overcome the drawbacks such as low automation and high cost, an approach for
      cell viability online detection is proposed, based on the extracted lensfree cell
      diffraction fingerprint characteristics. The cell fingerprints are acquired by a
      constructed large field-of-view (FOV) diffraction imaging platform without any
      lenses. The approach realizes distinguishing live and dead cells online and
      calculating cell viability index based on the number of live cells. With
      theoretical analysis and simulation, diffraction fingerprints of cells with
      different morphology are simulated and two characteristics are discovered to be
      able to reflect cell viability status effectively. Two parameters, fringe
      intensity contrast (FIC) and fringe dispersion (FD), are defined to quantify
      these two characteristics. They are verified to be reliable to identify live
      cells. In a cytotoxicity assay of different methyl mercury concentration on BRL
      cells, the proposed approach is used to detect cell viability. MTT method is also
      employed and the results of correlational analysis and Bland-Altman analysis
      prove the validity of the proposed approach. By comparison, it can be revealed
      that the proposed approach has some advantages over other present techniques.
      Therefore it may be widely used as a cell viability measurement method in drug
      screening, nutritional investigation and cell toxicology studies.

PMID- 29455027
TI  - Electrochemical detection of influenza virus H9N2 based on both immunomagnetic
      extraction and gold catalysis using an immobilization-free screen printed carbon
      microelectrode.
AB  - Influenza is a viral infectious disease considered as a source of many health
      problems and enormous socioeconomic disruptions. Conventional methods are
      inadequate for in-field detection of the virus and generally suffer from being
      laborious and time-consuming. Thus, studies aiming to develop effective
      alternatives to conventional methods are urgently needed. In this work, we
      developed an approach for the isolation and detection of influenza A virus
      subtype H9N2. For this aim, two specific influenza receptors were used. The
      first, anti-matrix protein 2 (M2) antibody, was attached to iron magnetic
      nanoparticles (MNPs) and used for the isolation of the virus from allantoic
      fluid. The second biomolecule, Fetuin A, was attached to an electrochemical
      detectable label, gold nanoparticles (AuNPs), and used to detect the virus
      tacking advantage from fetuin-hemagglutinin interaction. The MNP-Influenza virus
      AuNP formed complex was isolated and treated by an acid solution then the
      collected gold nanoparticles were deposited onto a screen printed carbon
      electrode. AuNPs catalyzes the hydrogen ions reduction in acidic medium while
      applying an appropriate potential, and the generated current signal was
      proportional to the virus titer. This approach allows the rapid detection of
      influenza virus A/H9N2 at a less than 16 HAU titer.

PMID- 29455028
TI  - Novel electrochemical biosensor based on cationic peptide modified hemin/G
      quadruples enhanced peroxidase-like activity.
AB  - This work designed an artificial substrate peptide to synthesize peptide-hemin/G
      quadruplex (peptide-DNAzyme) conjugates. In addition to enhancing catalytic
      activity of hemin/G-quadruplex, the peptide could also be induced and cleaved by
      prostate specific antigen (PSA). It was the first report on peptide-DNAzyme
      conjugates in application of the peptide biosensor. The polyethyleneimine-reduced
      graphene oxide@hollow platinum nanotubes (PEI-rGO@PtNTs) nanocomposites were cast
      on the glassy carbon electrode in order to form the interface of biocompatibility
      and huge surface area for bioprobes immobilization. In absence of PSA, the
      peptide-DNAzyme conjugates retained intact on the surface of the electrode to
      produce a strong response signal. But in presence of PSA, the peptide-DNAzyme
      conjugates were destroyed to release electron mediators, resulting in dramatical
      decrease of the electrochemicl signal. Therefore, the method had high sensitivity
      and super selectivity with the limit of detection calculated as 2.0 fg/mL.
      Furthermore, the strategy would be promising to apply for other proteases by
      transforming the synthetic peptide module of target.

PMID- 29455030
TI  - The clinical significance and biological function of tropomyosin 4 in colon
      cancer.
AB  - Tropomyosin 4 (TPM4) has been found to be dys-regulated, and function as oncogene
      or anti-oncogene in human cancers. However, there was no report on the clinical
      significance and biological function of TPM4 in colon cancer. This study was
      designed to investigate the clinical value and biological function of TPM4 in
      colon cancer. Thus, we detected the TPM4 expression in colon cancer clinical
      samples, and conducted the gain-of-function in colon cancer cell lines. In our
      results, TPM4 mRNA and protein expressions were reduced in colon cancer tissues
      and cell lines compared with normal colon tissues and colon epithelial cell line,
      respectively. TPM4 protein low-expression was obviously associated with clinical
      stage, T classification (invasion depth), N classification (lymph node
      metastasis), distant metastasis and differentiation. Survival analysis showed low
      expression of TPM4 was an unfavorable independent prognostic factor for colon
      cancer patients. Moreover, the experiments in vitro suggested up-regulated TPM4
      expression suppressed colon cancer cell migration, invasion and metastasis
      associated gene expression including MMP-2, MMP-9 and MT1-MMP, but had no effect
      on cell proliferation. In conclusion, TPM4 is associated with clinical
      progression in colon cancer patient and acts as a tumor suppressor in colon
      cancer cell.

PMID- 29455029
TI  - Heterogeneous patterns of brain atrophy in Alzheimer's disease.
AB  - There is increasing evidence showing that brain atrophy varies between patients
      with Alzheimer's disease (AD), suggesting that different anatomical patterns
      might exist within the same disorder. We investigated AD heterogeneity based on
      cortical and subcortical atrophy patterns in 299 AD subjects from 2 multicenter
      cohorts. Clusters of patients and important discriminative features were
      determined using random forest pairwise similarity, multidimensional scaling, and
      distance-based hierarchical clustering. We discovered 2 typical (72.2%) and 3
      atypical (28.8%) subtypes with significantly different demographic, clinical, and
      cognitive characteristics, and different rates of cognitive decline. In contrast
      to previous studies, our unsupervised random forest approach based on cortical
      and subcortical volume measures and their linear and nonlinear interactions
      revealed more typical AD subtypes with important anatomically discriminative
      features, while the prevalence of atypical cases was lower. The hippocampal
      sparing and typical AD subtypes exhibited worse clinical progression in
      visuospatial, memory, and executive cognitive functions. Our findings suggest
      there is substantial heterogeneity in AD that has an impact on how patients
      function and progress over time.

PMID- 29455031
TI  - Whole-word frequency and inflectional paradigm size facilitate Estonian case
      inflected noun processing.
AB  - Estonian is a morphologically rich Finno-Ugric language with nominal paradigms
      that have at least 28 different inflected forms but sometimes more than 40. For
      languages with rich inflection, it has been argued that whole-word frequency, as
      a diagnostic of whole-word representations, should not be predictive for lexical
      processing. We report a lexical decision experiment, showing that response
      latencies decrease both with frequency of the inflected form and its inflectional
      paradigm size. Inflectional paradigm size was also predictive of semantic
      categorization, indicating it is a semantic effect, similar to the morphological
      family size effect. These findings fit well with the evidence for frequency
      effects of word n-grams in languages with little inflectional morphology, such as
      English. Apparently, the amount of information on word use in the mental lexicon
      is substantially larger than was previously thought.

PMID- 29455032
TI  - Sevoflurane for procedural sedation in critically ill patients: A pharmacokinetic
      comparative study between burn and non-burn patients.
AB  - BACKGROUND: Sevoflurane has anti-inflammatory proprieties and short lasting
      effects making it of interest for procedural sedation in critically ill patients.
      We evaluated the pharmacokinetics of sevoflurane and metabolites in severely ill
      burn patients and controls. The secondary objective was to assess potential
      kidney injury. METHODS: Prospective interventional study in a burn and a surgical
      intensive care unit; 24 mechanically ventilated critically ill patients (12
      burns, 12 controls) were included. The sevoflurane was administered with an
      expired fraction target of 2% during short-term procedural sedation. Plasma
      concentrations of sevoflurane, hexafluoroisopropanolol (HFIP) and free fluoride
      ions were recorded at different times. Kinetic Pro (Wgroupe, France) was used for
      pharmacokinetic analysis. Kidney injury was assessed with neutrophil gelatinase
      associated lipocalin (NGAL). RESULTS: The mean total burn surface area was 36+/
      11%. The average plasma concentration of sevoflurane was 70.4+/-37.5mg.L-1 in
      burns and 57.2+/-28.1mg.L-1 in controls at the end of the procedure (P=0.58). The
      volume of distribution was higher (46.8+/-7.2 vs 22.2+/-2.50L, P<0.001), and the
      drug half-life longer in burns (1.19+/-0.28h vs 0.65+/-0.04h, P<0.0001). Free
      metabolite HFIP was higher in burns. Plasma fluoride was not different between
      burns and controls. NGAL did not rise after procedures. CONCLUSION: We observed
      an increased volume of distribution, slower elimination rate, and altered
      metabolism of sevoflurane in burn patients compared to controls. Repeated use for
      procedural sedation in burn patients needs further evaluation. No renal toxicity
      was detected. TRIAL REGISTRY NUMBER: ClinicalTrials.gov Identifier NCT02048683.

PMID- 29455033
TI  - Thromboprophylaxis for ambulatory surgery: Results from a prospective national
      cohort.
AB  - BACKGROUND: Venous thromboembolism (VTE) prophylaxis is not always part of the
      usual care of ambulatory surgery patients, and few guidelines are available.
      OBJECTIVES: To collect data on the application of VTE prophylaxis in ambulatory
      patients. DESIGN: The OPERA study is a large national survey performed in 221
      healthcare facilities. PATIENTS: Among patients, 2174 who underwent one of ten
      selected procedures over two pre-defined days of investigation. MAIN OUTCOME
      MEASURES: Assessment and management of the postoperative VTE risk. RESULTS: The
      postoperative VTE risk was assessed as nil (4.1% of the physicians), low (74%) or
      moderate (20%). This risk was assessed as lower (71%) in ambulatory surgery as
      compared to conventional surgery. In most centres (94%), a personal patient
      history of VTE was recorded preoperatively, and in 72% a prophylaxis protocol was
      systematically applied but only 40% of the responding centres had a written
      protocol for VTE prophylaxis. The postoperative period (discharge at home) was
      covered by a VTE protocol for 75% of the centres, with VTE prophylaxis starting
      postoperatively in 21% of the patients. In these patients, different treatments
      were applied: below-knee compression stockings (25%); thigh-length compression
      stockings (21%); intermittent pneumatic compression in the recovery room (1.2%);
      unfractionated heparin (2.0%); low molecular weight heparins (65%); vitamin K
      antagonists (0.5%); other treatments, including direct oral anticoagulants
      (0.5%). CONCLUSION: These data underline the need for a better assessment of the
      VTE risk in ambulatory patients and new studies either with conventional or new
      agents to be able to build guidelines in this new setting.

PMID- 29455034
TI  - Preoperative risk factors for unexpected postoperative intensive care unit
      admission: A retrospective case analysis.
AB  - INTRODUCTION: The purpose of this retrospective case-control study was to
      investigate preoperative risk factors for unexpected postoperative intensive care
      unit (ICU) admissions in patients undergoing non-emergent surgical procedures in
      a tertiary medical centre. METHODS: A medical record review of adult patients
      undergoing elective non-cardiac and non-transplant major surgical procedures
      during the period of January 2011 through December 2015 in the operating rooms of
      a large university hospital was carried out. The primary outcome assessed was
      unexpected ICU admission, with mortality as a secondary outcome. Demographic
      data, length of hospital and ICU stay and preoperative comorbidities were also
      obtained as exposure variables. Propensity score matching was then employed to
      yield a study and control group. RESULTS: The group of patients who met inclusion
      criteria in the study and the control group that did not require ICU admission
      were obtained, each containing 1191 patients after propensity matching. Patients
      with acute and/or chronic kidney injury (odds ratio (OR) 2.20 [1.75-2.76]),
      valvular heart disease (OR: 1.94 [1.33-2.85]), peripheral vascular disease (PVD)
      (OR: 1.41 [1.02-1.94]) and congestive heart failure (CHF) (OR: 1.80 [1.31-2.46])
      were all associated with increased unexpected ICU admission. History of
      cerebrovascular accident (CVA) (OR: 3.03 [1.31-7.01]) and acute and/or chronic
      kidney injury (OR: 1.62 [1.12-2.35]) were associated with increased mortality in
      all patients; CVA was also associated with increased mortality (OR: 3.15 [1.21
      8.20]) specifically in the ICU population. CONCLUSIONS: CHF, acute/chronic kidney
      injury, PVD and valve disease were significantly associated with increased
      unexpected ICU admission; patients with CVA suffered increased mortality when
      admitted to the ICU.

PMID- 29455035
TI  - Sustainability of anaesthesia components of an enhanced recovery program (ERP) in
      colorectal and orthopaedics surgery.
AB  - BACKGROUND: Sustainability of ERP is a challenge and data are scarce on the
      subject. The aim of this study was to assess if application of enhanced recovery
      elements through the Francophone Group of Enhanced Recovery after Surgery (Grace)
      in the anaesthesia management was sustainable 2 years after its implementation.
      MATERIALS AND METHODS: We conducted a retrospective analysis of the prospective
      Grace database between October 2014 and October 2016. The evolution of each
      recommendation item over time was analysed using non-parametric Spearman
      correlation coefficient. RESULTS: A total of 67 and 43 centres corresponding to
      2067 and 3022 patients participated to the Grace audit in colorectal and
      orthopaedics surgery, respectively. Colorectal surgery: Mean length of stay was 5
      (+/-4) days and readmission rate was 6.6%. Application of most items did not
      statistically change. It worsened over time for PONV prophylaxis (P=0.01) and
      prevention of intraoperative hypothermia (P=0.02); and improved for NSAID
      administration (P=0.01). Orthopaedics surgery: Mean length of stay was 3 (+/-2)
      days and readmission rate was 1.7%. There was a trend towards improvement for
      most items. It reached statistical significance for PONV prophylaxis (P=0.001),
      limited preoperative fasting (P=0.01). While the use of a perineural catheter
      (P=0.001) decreased over time, infiltration of the surgical site statistically
      increased (P=0.05). CONCLUSION: This study shows on a large scale a trend towards
      less application of all ERP items over time. Continuous audits should be
      encouraged to expect further improvements.

PMID- 29455036
TI  - Short term post-operative morphing of sacrocolpopexy mesh measured by magnetic
      resonance imaging.
AB  - BACKGROUND: Sacrocolpopexy (SC) involves suspension of the vaginal vault or
      cervix to the sacrum using a mesh. Following insertion, the meshes have been
      observed to have undergone dimensional changes. OBJECTIVE: To quantify
      dimensional changes of meshes following implantation and characterize their
      morphology in-vivo. DESIGN SETTING AND PARTICIPANTS: 24 patients underwent SC
      using PolyVinyliDeneFluoride mesh loaded with Fe3O4 particles. Tailored anterior
      and posterior mesh flaps were sutured to the respective vaginal walls, uniting at
      the apex. The posterior flap continued to the sacrum and was attached there.
      Meshes were visualized on magnetic resonance (MR) imaging at 12 [3-12] (median
      [range]) months postoperatively and 3D models of the mesh were generated. Dynamic
      MR sequences were acquired during valsalva to record mesh mobility. OUTCOME
      MEASURES: The area of the vagina effectively supported by the mesh (Effective
      Support Area (ESA)) was calculated. The 3D models' wall thickness map was
      analyzed to identify the locations of mesh folding. Intraclass correlation (ICC)
      was calculated to test the reliability of the methods. To measure the laxity and
      flatness of the mesh, the curvature and the ellipticity of the sacral flap were
      calculated. RESULTS: The ESA calculation methodology had ICC = 0.97. A reduction
      of 75.49 [61.55-78.67] % (median [IQR]) in area, 47.64 [38.07-59.81] % in
      anterior flap, and of 23.95 [10.96-27.21] % in the posterior flap was measured.
      The mesh appeared thicker near its attachment at the sacral promontory (n = 19)
      and near the vaginal apex (n = 22). The laxity of the mesh was 1.13 [1.10-1.16]
      and 60.55 [49.76-76.25] % of the sacral flap was flat. We could not reliably
      measure mesh mobility (ICC = 0.16). CONCLUSION: A methodology for complete 3D
      characterization of SC meshes using MR images was presented. After implantation,
      the supported area is much lower than what is prepared prior to implantation. We
      propose this happened during the surgery itself.

PMID- 29455037
TI  - Physical-chemical properties of dental composites and adhesives containing silane
      modified SBA-15.
AB  - The aim of this study was to synthesize and characterize mesoporous materials SBA
      15 and SBA-15 modified with 3-(methacryloxy)-propyl-trimethoxysilane (MPS) to be
      used as inorganic filler in restorative dental composites and adhesives, and
      evaluate the main physical-chemical properties of the resulting material. The SBA
      15 and SBA-15/MPS were characterized by FTIR, BET and X-Ray and combined with
      TEGDMA, bis-GMA and commercial spherical silica to produce dental composites.
      Afterwards, the mesoporous materials were combined with TEGDMA, bis-GMA and HEMA
      to make adhesives. To compare the results, composites and adhesives containing
      only commercial spherical silica were investigated. Some physical-chemical
      properties such as degree of conversion (DC), flexural strength (FS) and modulus
      (FM), water sorption and solubility (Wsp and Wsl), specific area (BET), and the
      leachable components were evaluated. The SBA-15/MPS can be used to prepare dental
      restorative materials, with some foreseeable advantages compared with pure SBA-15
      dental materials and with improved properties compared with commercial spherical
      silica dental materials. An important improvement was that the dental materials
      based on modified SBA-15 presented a reduction of approximately 60% in leaching
      of unreacted monomers extracted by solvent compared to the control group.

PMID- 29455038
TI  - Mechanical and degradation property improvement in a biocompatible Mg-Ca-Sr alloy
      by thermomechanical processing.
AB  - Magnesium-based alloys have attracted interest as a potential material to
      comprise biomedical implants that are simultaneously high-strength and temporary,
      able to provide stabilization before degrading safely and able to be excreted by
      the human body. Many alloy systems have been evaluated, but this work reports on
      improved properties through hot extrusion of one promising alloy: Mg-1.0 wt% Ca
      0.5 wt%Sr. This alloy has previously demonstrated promising toxicity and
      degradation properties in the as-cast and rolled conditions. In the current study
      extrusion causes a dramatic improvement in the mechanical properties in tension
      and compression, as well as a low in vitro degradation rate. Microstructure
      (texture, second phase distribution, and grain size), bulk mechanical properties,
      flow behavior, degradation in simulated body fluid, and effect on osteoblast
      cyctotoxicity are evaluated and correlated to extrusion temperature. Maximum
      yield strength of 300 MPa (above that of annealed 316 stainless steel) with 10%
      elongation is observed, making this alloy competitive with existing implant
      materials.

PMID- 29455039
TI  - Comparison of different constitutive models to characterize the viscoelastic
      properties of human abdominal adipose tissue. A pilot study.
AB  - Knowing the mechanical properties of human adipose tissue is key to simulate
      surgeries such as liposuction, mammoplasty and many plastic surgeries in which
      the subcutaneous fat is present. One of the most important surgeries, for its
      incidence, is the breast reconstruction surgery that follows a mastectomy. In
      this case, achieving a deformed shape similar to the healthy breast is crucial.
      The reconstruction is most commonly made using autologous tissue, taken from the
      patient's abdomen. The amount of autologous tissue and its mechanical properties
      have a strong influence on the shape of the reconstructed breast. In this work,
      the viscoelastic mechanical properties of the human adipose tissue have been
      studied. Uniaxial compression stress relaxation tests were performed in adipose
      tissue specimens extracted from the human abdomen. Two different viscoelastic
      models were used to fit to the experimental tests: a quasi-linear viscoelastic
      (QLV) model and an internal variables viscoelastic (IVV) model; each one with
      four different hyperelastic strain energy density functions to characterise the
      elastic response: a 5-terms polynomial function, a first order Ogden function, an
      isotropic Gasser-Ogden-Holzapfel function and a combination of a neoHookean and
      an exponential function. The IVV model with the Ogden function was the best
      combination to fit the experimental tests. The viscoelastic properties are not
      important in the simulation of the static deformed shape of the breast, but they
      are needed in a relaxation test performed under finite strain rate, particularly,
      to derive the long-term behaviour (as time tends to infinity), needed to estimate
      the static deformed shape of the breast. The so obtained stiffness was compared
      with previous results given in the literature for adipose tissue of different
      regions, which exhibited a wide dispersion.

PMID- 29455040
TI  - A simple method for calculating the likelihood ratio in a kinship test using X
      chromosomal markers incorporating linkage, linkage disequilibrium, and mutation.
AB  - X-chromosomal short tandem repeats (X-STRs) are useful for personal
      identification and kinship tests. However, it has not yet been fully established
      how to incorporate linkage and linkage disequilibrium (LD) into the calculation
      of the likelihood ratio (LR). In this paper, we describe a simple calculation
      method of LR for X-STRs that incorporated linkage, LD, and mutations. Initially,
      Japanese population data of 27 X-STRs (DXS6807, DXS9902, DXS6795, DXS6810,
      DXS10076, DXS10077, DXS10078, DXS10162, DXS10163, DXS10164, DXS7132, DXS981,
      DXS6800, DXS6803, DXS6809, DXS6789, DXS6799, DXS7424, DXS101, DXS7133,
      GATA172D05, DXS10103, HPRTB, GATA31E08, DXS8377, DXS10147, and DXS7423) were
      collected from 748 unrelated individuals to estimate the influence of LD.
      Significant LD was observed on six pairs of loci. Subsequently, using the
      population data, a simulation study was performed to evaluate the validity of the
      present calculation method for LR in cases of father-daughter, full-sisters,
      paternal half-sisters, maternal half-sisters, and unrelated pairs of females (FD,
      FS, PHS, MHS, and UR, respectively). As a result, the distribution of LR among FD
      was completely separated from that among UR. In the sibship test, 98.6% of FS and
      98.0% of PHS surpassed the maximum value of UR in combined LR. Even in the FS
      versus MHS setting, 60.5% of FS had a higher LR than any MHS. We conclude that
      the present model is powerful in discriminating the relationship and is able to
      obtain a reasonable LR with fewer computations.

PMID- 29455041
TI  - Is OSNA better than imprint cytology for intraoperative diagnosis of cancer
      involvement of axillary sentinel node in breast cancer?
AB  - OBJECTIVE: The study aim was to establish Sensitivity, Specificity, Positive
      Predictive Value, Negative Predictive Value (NPV), and Accuracy Values of both
      imprint cytology (IC) and the OSNA assay for intraoperative assessment of
      axillary sentinel node (SN) cancer involvement in breast cancer. Specifically, we
      wished to find out if true positive and false negative results of IC were
      associated to axillary lymphadenectomy (ALND). Also, we addressed a comparative
      cost analysis between techniques. METHODS: 244 patients treated for breast cancer
      in the Breast Unit of Hospital Germans Trias i Pujol from 2011 to 2015 were
      prospectively included. A transversal, consecutive design was applied to assess
      IC compared to the reference test (OSNA). Inclusion criteria were: T1 and T2
      tumors with negative nodes, both clinically and on ultrasound. RESULTS:
      Sensitivity of IC for macrometastases was 70%. The NPV of IC for macrometastases
      was 95,75%. Accuracy of IC was 96,12%. In the comparative cost analysis, the
      release time of results for OSNA doubled that of IC and was associated with an
      increased cost of ? 370. CONCLUSIONS: IC has been stated as a good technique for
      intraoperative cancer involvement SN with high sensitivity and NPV compared to
      the OSNA assay. It allows keeping the whole node tissue and thus the possibility
      of improved histopathological evaluation, which can be useful for adjuvant, and
      offers the advantage of being less time consuming. Cost analysis shows a higher
      cost for OSNA, which may exceed the benefit of sorting out false negatives from
      IC.

PMID- 29455042
TI  - Trapping of 1,2-cyclohexadiene: A DFT mechanistic study on the reaction of 1,2
      cyclohexadiene with olefins and nitrones.
AB  - The mechanistic aspects of cycloaddition reactions of 1,2-cyclohexadiene with
      olefins and nitrones have been investigated with DFT calculations. The results
      show that the cycloaddition reactions of 1,2-cyclohexadiene with olefins do not
      go through a concerted pathway (one-step mechanism) but rather a stepwise one
      involving the formation of a biradical intermediate which then closes to form
      final cycloadduct. Electron-withdrawing substituents on the 1,2-cyclohexadiene
      decrease the activation barrier of the biradical-forming step but increase the
      barrier of the product-forming step and product stability, while electron
      donating substituents on the 1,2-cyclohexadiene increase the barriers for both
      the biradical-forming step and the product-forming step but decrease the product
      stability. In the reaction of 1,2-cyclohexadiene with nitrones, the four pathways
      investigated have activation barriers within 1 kcal/mol of one another, the
      lowest being 10.45 kcal/mol and the highest 11.04 kcal/mol, indicating that these
      reactions are very unselective. Electron-withdrawing groups on the nitrone
      increase the stability of the resulting products whereas electron-donating group
      on the nitrone decrease the stability of the resulting products. The [3 + 2]
      cycloadduct proceeds to the formation of a more stable formal [5 + 2] cycloadduct
      if a phenyl substituent is present on the nitrogen of the nitrone.

PMID- 29455043
TI  - Ultra-early injection of low-viscosity cement in vertebroplasty procedure for
      treating osteoporotic vertebral compression fractures: A retrospective cohort
      study.
AB  - OBJECTIVE: To evaluate the clinical effect of ultra-early injection (before the
      phase of "tooth-paste-like") of low-viscosity cement in percutaneous
      vertebroplasty (PVP) for treating osteoporotic vertebral compression fractures
      (OVCFs). METHODS: Two hundred sixty-one patients who had PVP procedures with low
      viscosity cement (ultra-early injection: 145, normal injection: 135) were
      included from July 2010 to July 2016 in our hospital. Visual Analog Scale (VAS),
      Oswestry Disability Index (ODI), Cobb angle, cement leakage, and adjacent
      vertebral fractures were evaluated. The follow-up period was over 12 months.
      RESULTS: VAS 3.0 d after surgery was significantly reduced in the ultra-early
      injection group compared to that in the control group (P = 0.00), but no
      difference was found at the final follow-up (P = 0.53). Similar results were
      found for ODI. The Cobb angle in both groups was recovered after PVP (P < 0.05);
      however, in the control group, the Cobb angle at the final follow-up was
      significantly increased compared with that 3.0 d after surgery (P = 0.00). There
      was a significant difference in the Cobb angle between the two groups at the
      final follow-up (P = 0.00). Regarding cement leakage, there were no significant
      differences in terms of mild (P = 0.58), moderate (P = 0.68), or severe leakage
      (P = 0.52). Seven patients in the control group had adjacent vertebral fractures,
      but only one patient in the ultra-early injection group experienced adjacent
      fractures (P = 0.03). CONCLUSIONS: Ultra-early injection of low-viscosity cement
      during PVP procedures in the treatment of OVCFs not only quickly and
      significantly relieves pain, reduces the incidence of adjacent vertebral
      fractures, and prevents progressive kyphotic deformity, but also does not
      increase the risk of cement leakage when compared with that of the traditional
      injection procedure.

PMID- 29455044
TI  - Timing of surgical site infection and pulmonary complications after laparotomy.
AB  - BACKGROUND: Surgical site infection (SSI) and other postoperative complications
      are associated with high costs, morbidity, secondary surgery, and mortality. Many
      studies have identified factors that may prevent SSI and pulmonary complications,
      but it is important to know when they in fact occur. The aim of this study was to
      investigate the diagnostic timing of surgical site infections and pulmonary
      complications after laparotomy. MATERIAL AND METHODS: This is a secondary
      analysis of the PROXI trial which was a randomized clinical trial conducted in
      1400 patients undergoing elective or emergent laparotomy. Patients were randomly
      allocated to either 80% or 30% perioperative inspiratory oxygen fraction.
      RESULTS: SSI or pulmonary complications were diagnosed in 24.2% (95% CI: 22.0%
      26.5%) of the patients at a median of 9 days [IQR: 5-15] after surgery. Most
      common was surgical site infection (19.6%); median time 10 days after surgery
      [IQR: 7-18]. The corresponding figures for anastomotic leakage was 5.7%, 8 days
      [IQR: 6-10]; pneumonia 3.5%, 5 days [IQR: 3-9]; and respiratory failure 2.3%, 3
      days [IQR: 1-8]. The oxygen allocation was not significantly related to time of
      diagnosis for postoperative surgical site infections or pulmonary complications.
      CONCLUSION: A high percentage of patients undergoing laparotomy develop a
      postoperative complication. This study adds new knowledge by identifying time
      intervals within which medical professionals should be aware of surgical site
      infections and pulmonary complications in order to initiate appropriate treatment
      of the patients.

PMID- 29455045
TI  - Impact of transvaginal modified sacrospinous ligament fixation with mesh for the
      treatment of pelvic organ prolapse-before and after studies.
AB  - BACKGROUND: Pelvic organ prolapse (POP) is a common disease in women. The aim of
      this research was to evaluate the safety, efficacy and complication of
      transvaginal modified sacrospinous ligament fixation with mesh using for the
      treatment of vaginal vault prolapse. MATERIALS AND METHODS: This was a
      prospective study including information from 60 symptomatic women with anterior
      apical pelvic floor prolapse. The patients underwent transvaginal modified
      sacrospinous ligament fixation combined with anterior vaginal wall mesh between
      May 2014 and Sep 2015. The perioperative data including clinical characteristic,
      operation time, blood loss, and surgical complications were collected at 1 year
      and 2 years. During a 2-year follow-up, the primary outcome evaluation included
      Pelvic organ prolapse Quantification system (POP-Q), Incontinence Quality of Life
      scale (I-QoL), the Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12)
      and the Pelvic Floor Distress Inventory, short form 20 (PFDI-20). RESULTS: The
      mean follow-up time was 2 years (range 24-37 months). The patients' mean age was
      66.75 +/- 6.44. Of 60 patients who were enrolled in this research, 26 patients
      had severe stress urinary incontinence (SUI). The mean operation time was 99.14
      +/- 19.60 min and the mean estimated blood loss was 73.83 +/- 41.05 ml. The rate
      of anatomical success was 98.3% and one patient had a recurrence. The POP-Q point
      measurements were evaluated preoperatively and postoperatively (P < 0.001).
      Moreover, the quality of life and sexual activity were all improved
      postoperatively via I-QoL, PISQ-12 and PFDI-20 scores (P < 0.001). There was no
      injury to the rectum, bladder, major pelvic vessels and pudendal nerves. However,
      18 patients had postoperative complications. CONCLUSIONS: This study showed that
      transvaginal modified sacrospinous ligament fixation with mesh might be performed
      easily and might be a safe surgery for elderly patients whose requirements for
      sexual life were relatively low. Further researches were required to investigate
      its long-term efficacy.

PMID- 29455046
TI  - Evaluation of surgical outcome in advanced age patients with developmental hip
      dysplasia.
AB  - BACKGROUND: This study aimed at determining the efficacy of the surgical
      treatment conducted on children with delayed presentation developmental dysplasia
      of the hip (DDH). The objective was to provide a good comparison of functional
      and radiographic outcomes and to determine various surgical treatment options.
      METHOD: In this study, we evaluated the results of 38 hips of 27 patients aged 4
      years onset which had been operated due to DDH. Radiographic outcomes were
      evaluated by using acetabular index, CE angle, Tonnis and the Severin
      classification system. Clinical evaluation was made by using IOWA hip scores.
      Degenerative changes were evaluated according to Boyer and avascular necrosis
      according to Kalamchi-MacEwen criteria. RESULTS: The mean age of the patients at
      the operation time was 10 years 3 months (range: 4 years 3 months-30 years).
      While the mean acetabular index was 37.97 preoperatively, in the last follow-up
      it was 19.92. Thirty-six hips (94%) had an excellent and good outcomes, and two
      hips (%6) had a fair outcome with respect to the Severin criteria. The mean hip
      score with respect to IOWA was 93.736 (range: 75-98) and the rate of excellent
      and good outcomes was 98%. CONCLUSION: For the treatment of patients with DDH of
      late onset, a one-staged operative procedure is recommended. This method is
      applied successfully and enables us to achieve good clinical and radiographic
      results.

PMID- 29455047
TI  - Prospective cohort study of neoadjuvant therapy toxicity in the treatment of
      oesophageal adenocarcinoma.
AB  - BACKGROUND: Early studies investigating the benefits of neoadjuvant therapy in
      oesophageal cancer showed conflicting results, taking many years before a
      survival advantage was demonstrated in randomised trials. Gains are modest,
      limited by progressive disease and toxicity. This study aimed to investigate the
      relationship between neoadjuvant therapy-associated toxicity and clinical
      outcomes including survival in patients with potentially curable oesophageal
      adenocarcinoma. MATERIALS AND METHODS: A cohort of 286 patients undergoing
      neoadjuvant therapy followed by surgical resection at a single institution was
      identified from a prospective database. Adverse events from neoadjuvant therapy
      were recorded and graded. Patients were divided into two groups according to
      whether they suffered toxicity or not. Clinical outcomes including whether
      patients completed the neoadjuvant course, whether they proceeded to resection
      and overall survival, were compared between the groups. RESULTS: Neoadjuvant
      therapy-related toxicity was identified in 67/286 patients. 46 patients suffered
      severe, life-threatening or fatal adverse events. In patients with toxicity, 47%
      did not complete the chemotherapy course compared to 17% without toxicity, RR 2.7
      (95%CI 1.7-4.4), (P < 0.001). In patients suffering toxicity, 17.9% failed to
      proceed to resection compared with 7.8% in those without toxicity, RR 2.3 (95%CI
      1.2-4.6) P = 0.02. Median overall survival was shorter in patients suffering
      toxicity (20.7 months) compared to those without toxicity (37.8 months), P =
      0.008. When patients failing to proceed to resection were excluded, median
      overall survival was shorter in patients suffering toxicity (26.2 months)
      compared with those without toxicity (47.8), P = 0.039. CONCLUSION: Neoadjuvant
      therapy-related toxicity is common and can have serious consequences including
      failure to complete chemotherapy cycles, a higher risk of not proceeding to
      surgical resection and poorer overall survival. Efforts should be made to reduce
      toxicity and research should aim to identify responders and factors predictive of
      toxicity.

PMID- 29455048
TI  - A clinical prediction score to determine surgical drainage of deep neck
      infection: A retrospective case-control study.
AB  - BACKGROUND: The objective of this retrospective study was to identify predictors
      of an abscess guaranteed to be surgically drained successfully in patients with
      deep neck infection (DNI). MATERIALS AND METHODS: We divided 97 consecutive
      patients with DNI into a drained group and a non-drained group. We then developed
      a clinical prediction score and validated it in 32 further patients. RESULTS:
      Significant predictors of successful surgical drainage (i.e., positive for pus)
      were rim enhancement on computed tomography, C-reactive protein, erythrocyte
      sedimentation rate, and the neutrophil to lymphocyte ratio. The estimated cut-off
      values (excluding rim enhancement, which is a yes/no parameter) were 41.25, 56.5,
      and 8.02, respectively, and the clinical prediction score for each of the four
      other factors was determined to be 2, 2, 3, and 3 points, respectively. The cut
      off score for the sum of these points was 6.5 and the scoring system had an
      accuracy of 87.5% in the validation group. CONCLUSION: Our clinical prediction
      scoring system can predict whether drainage is successful in patients with DNI.

PMID- 29455049
TI  - Poststroke epilepsy following transient unilateral middle cerebral and common
      carotid artery occlusion in young adult and aged F344 rats.
AB  - The mechanisms of injured brain that establish poststroke seizures and epilepsy
      are not well understood, largely because animal modeling has had limited
      development. The main objective of this study was to determine whether an
      arterial occlusion model of cortical stroke in young adult and aged rats was
      capable of generating either focal or generalized epileptic seizures within 2
      months of lesioning. Four- and 20-month-old male Fischer 344 (F344) sham-operated
      controls and those lesioned by transient (3 h) unilateral middle cerebral artery
      (MCA) and common carotid artery (CCA) occlusion (MCA/CCAo) were studied by video
      EEG recordings up to 2 months post-procedure. The main findings were: 1) seizures
      (grade 3 and above) were recorded within 2 months in both young (4-month; 0.23/h)
      and aged (20-month; 1.93/h) MCA/CCAo rat groups; both MCA/CCAo rat groups had
      more seizures recorded than the respective control groups, i.e., no seizures in
      young controls and 0.52/h in old controls; 2) both age and infarction
      independently had effects on seizure frequency; however, there was no
      demonstrated interaction between the two factors; and 3) there was no difference
      in infarct volumes comparing 4- to 20-month-old MCA/CCAo animals. In addition,
      all lesioned and sham-operated animals demonstrated intermittent solitary
      myoclonic convulsions arising out of sleep. Morbidity and mortality of animals
      limited the extent to which the animals could be evaluated, especially 20-month
      old animals. These results suggest that transient unilateral MCA/CCAo can result
      in poststroke epileptic seizures in both young adult and aged F344 rats within a
      relatively brief period of time following lesioning.

PMID- 29455051
TI  - Editorial: Utilization of data from air quality monitoring networks.

PMID- 29455050
TI  - Targeted gene panel and genotype-phenotype correlation in children with
      developmental and epileptic encephalopathy.
AB  - OBJECTIVE: We performed targeted gene-panel sequencing for children with
      developmental and epileptic encephalopathy (DEE) and evaluated the clinical
      implications of genotype-phenotype correlations. METHODS: We assessed 278
      children with DEE using a customized gene panel that included 172 genes, and
      extensively reviewed their clinical characteristics, including therapeutic
      efficacy, according to genotype. RESULTS: In 103 (37.1%) of the 278 patients with
      DEE, 35 different disease-causing monogenic mutations were identified. The
      diagnostic yield was higher among patients who were younger at seizure onset,
      especially those whose seizures started during the neonatal period, and in
      patients with drug-resistant epilepsy. According to epilepsy syndromes, the
      diagnostic yield was the highest among patients with West syndrome (WS) with a
      history of neonatal seizures and mutations in KCNQ2 and STXBP1 were most
      frequently identified. On the basis of genotypes, we evaluated the clinical
      progression and seizure outcomes with specific therapeutic regimens; these were
      similar to those reported previously. In particular, sodium channel blockers were
      effective in patients with mutations in KCNQ2 and SCN2A in infancy, as well as
      SCN8A, and interestingly, the ketogenic diet also showed diverse efficacy for
      patients with SCN1A, CDKL5, KCNQ2, STXBP1, and SCN2A mutations. Unfortunately,
      quinidine was not effective in 2 patients with migrating focal epilepsy in
      infancy related to KCNT1 mutations. CONCLUSION: Targeted gene-panel sequencing is
      a useful diagnostic tool for DEE in children, and genotype-phenotype correlations
      are helpful in anticipating the clinical progression and treatment efficacy among
      these patients.

PMID- 29455052
TI  - An instrumental variables approach to assess the effect of class size reduction
      on student screen time.
AB  - An emerging area of research considers links between characteristics of the
      school setting and health. The existing small evidence base assessing the
      association between class size and health is inconclusive. This quasi
      experimental study uses an instrumental variables approach based on North
      Carolina's elementary class size reduction policy to assess the relationship
      between class size and student screen time. Specifically, data are from public
      school students in North Carolina, USA, who were in 3rd grade any time between
      fall 2005 and spring 2011. There was no association between class size and screen
      time (measured as recreational television and/or electronic device use), after
      accounting for grade size and school size, year fixed effects, and clustering at
      the school and district level. These findings suggest that, in statewide policy
      implementation settings, there may not be any immediate spillover benefits of
      class size reduction policies on student screen time.

PMID- 29455053
TI  - The becoming of methadone in Kenya: How an intervention's implementation
      constitutes recovery potential.
AB  - This analysis treats the recent introduction of methadone treatment in Kenya as a
      case of 'evidence-making intervention'. Using 30 qualitative interviews with
      people in receipt of methadone treatment in Nairobi, Kenya, methadone's becoming
      is treated as an effect of its narrative and material implementations. The
      interviews are shown to enact a narrative of methadone recovery potential towards
      normalcy beyond addiction. Such recovery potential is materialised in practice
      through social interactions wherein methadone's embodied effects are seen to be
      believed. Here, the recovering body affects others' recovery potential. In a
      context of competing claims about methadone's effects, including the circulation
      of doubt about experimenting with methadone treatment, embodied methadone effect
      helps moderate the multiverse of methadone knowledge. The material dynamics of
      methadone treatment delivery also affect its recovery potential, with the
      methadone queue enacting a rationing of recovery hope. Here, the experience of
      methadone's implementation loops back to a life with drugs. I conclude that there
      is a coexistence of potentiality and actuality, a 'methadone multiple', produced
      through its narrative and material implementations.

PMID- 29455054
TI  - Seco-labdane diterpenoids from the leaves of Callicarpa nudiflora showing nitric
      oxide inhibitory activity.
AB  - Nine previously undescribed seco-labdane diterpenoids, nudiflopenes A-I, were
      isolated from the leaves of Callicarpa nudiflora. Their structures were
      elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis,
      and the absolute configurations of these compounds were established by the
      modified Mosher's method and experimental and calculated electronic circular
      dichroism spectra. Nudiflopenes A-I belong to the class of seco-labdane
      diterpenoids. All of the isolates showed inhibitory activities on
      lipopolysaccharide-induced nitric oxide (NO) production in murine microglial BV-2
      cells. The possible mechanism of NO inhibition of some bioactive compounds was
      also investigated using molecular docking, which revealed interactions of
      bioactive compounds with the inducible nitric oxide synthase (iNOS) protein.

PMID- 29455055
TI  - Specificity of glycosaminoglycan-protein interactions.
AB  - Glycosaminoglycans (GAGs) interact with a variety of proteins with important
      functions in development and homeostasis. Most of these proteins bind to heparin
      in vitro, a highly sulfated GAG species, although heparan sulfate and/or
      chondroitin/dermatan sulfate are more frequent physiological ligands. Binding
      affinity and specificity are determined by charge distribution, mainly due to
      sulfate and carboxylate groups and by GAG chain conformation. Interactions may be
      nonspecific, essentially reflecting charge density or highly specific, dependent
      on rare GAG-structural features. Yet other GAG epitopes bind protein ligands with
      intermediate specificity and variable affinity. Studies of heparan sulfate
      biosynthesis point to stochastic but strictly regulated, cell-specific polymer
      modification. Together, these features allow for graded modulation of protein
      functional response.

PMID- 29455056
TI  - Bringing diffuse X-ray scattering into focus.
AB  - X-ray crystallography is experiencing a renaissance as a method for probing the
      protein conformational ensemble. The inherent limitations of Bragg analysis,
      however, which only reveals the mean structure, have given way to a surge in
      interest in diffuse scattering, which is caused by structure variations. Diffuse
      scattering is present in all macromolecular crystallography experiments. Recent
      studies are shedding light on the origins of diffuse scattering in protein
      crystallography, and provide clues for leveraging diffuse scattering to model
      protein motions with atomic detail.

PMID- 29455058
TI  - Physical activity combined with resistance training reduces symptoms of frailty
      in older adults: A randomized controlled trial.
AB  - INTRODUCTION: Increased physical activity (PA) is a crucial factor in the
      prevention of physical deterioration, and resistance training (RT) is also a
      common and effective intervention for older adults. However, the effects of PA as
      an adjunct to RT on frailty status remains unclear; therefore, we clarified the
      effect of a PA intervention with feedback, as an adjunct to resistance strength
      training, on the physical and mental outcomes of frail older adults. MATERIALS
      AND METHODS: We employed a randomized controlled trial. Community-dwelling frail
      older adults in Japan were recruited to participate. Forty-one participants (mean
      age 81.5) were randomly assigned to engage in a resistance training with PA (RPA
      group) or RT group for six months. Frailty status and frailty scores, which were
      measured according to the Cardiovascular Health Study criteria-muscle strength,
      mobility, instrumental activities of daily living, and health-related quality of
      life-were assessed. RESULTS: Participants in the RPA group exhibited a
      significant increase in light-intensity PA, the number of steps taken daily (p <
      0.05), and lower-limb muscle strength (p < 0.05) and a significant decrease in
      frailty scores. However, pre- and postintervention frailty status, instrumental
      activities of daily living, and health-related quality of life did not differ
      significantly. CONCLUSIONS: Implementation of a PA intervention as an adjunct to
      RT is feasible, as it reduced frailty scores and increased lower-limb muscle
      strength and mobility in older adults with frailty symptoms.

PMID- 29455057
TI  - The impact of body composition, pain and resilience on physical activity,
      physical function and physical performance at 2 months post hip fracture.
AB  - The purpose of this study was to test a model of the factors influencing physical
      activity, physical function and physical performance at 2 months post hip
      fracture and compare model fit between men and women. Age, cognitive status,
      comorbidities, pain, resilience, bone mineral density, total body lean mass,
      total body fat and grip strength were hypothesized to be directly and/or
      indirectly related to physical activity, physical function and physical
      performance. This analysis used data from the seventh Baltimore Hip Studies (BHS
      7), a prospective cohort study that included 258 community-dwelling participants,
      125 (48%) men and 133 (52%) women, hospitalized for treatment of a hip fracture;
      survey and objective data were obtained at 2 months post hip fracture. In
      addition to age, sex and comorbidities (modified Charlson scale), data collection
      included body composition from dual-energy x-ray absorptiometry (DXA) scans, grip
      strength, and physical activity, function and performance based on the Yale
      Physical Activity Survey, the Short Physical Performance Battery and the Lower
      Extremity Gain Scale. Age, cognition, and comorbidities were not significantly
      associated with resilience; and, resilience was not associated with pain. In
      addition, bone mineral density was not associated with physical activity,
      physical performance or physical function. Total lean body mass, resilience and
      pain were associated with physical activity, physical function and physical
      performance in women, but were not consistently associated with physical and
      functional outcomes in men. Future research should consider evaluation of muscle
      quality and additional psychosocial factors (e.g., depression, social supports)
      in model testing.

PMID- 29455060
TI  - Major depressive disorder and depressive symptoms in intermittent explosive
      disorder.
AB  - It is estimated that between 1.7 and 2.6 million people have had intermittent
      explosive disorder (IED) during their life in the United States alone. Co
      occurring psychiatric disorders are very common in IED, being major depressive
      disorder arguably the most common. The objective of this study was to examine the
      clinical correlates of IED and depressive manifestations in 74 treatment-seeking
      subjects. After controlling for confounders, there were associations between
      major depressive disorder and severity of depressive symptoms, and (a) higher
      assault scores, (b) more severe hostile behavior and (c) worse social adjustment.
      Management of depressive symptoms may be an important for IED treatment.

PMID- 29455059
TI  - The impact of infection on mortality in octogenarians who were admitted due to
      acute coronary syndrome.
AB  - BACKGROUND: The prevalence of coronary artery disease is on the rise as the life
      expectancy of the population increases. However, treatment of acute coronary
      syndrome in the elderly patients has its own problems that have not been
      thoroughly addressed in the clinical trials. Since these patients are generally
      fragile and have multiple co-morbidities, the course of acute coronary syndrome
      can frequently be complicated. Infection, which co-exists either at the initial
      presentation or is acquired during the hospital stay, is a condition about which
      there is little published data. Therefore, in our study, we wanted to assess the
      impact of infection on mortality in octogenarians who have acute coronary
      syndrome METHODS: We retrospectively analyzed the data of 174 octogenarians who
      had been admitted to the coronary care unit with acute coronary syndrome. All
      cause mortality was defined as the primary endpoint of the study. RESULTS:
      Overall 53 octogenarian patients (30.5%) had an infection along with acute
      coronary syndrome. The mean duration of follow-up was 10 months (1-25 months).
      Both in-hospital and long-term mortality were higher in these patients (18.9% vs
      6.6%, p = 0.01; 52.8% vs 27.5%, p < 0.01; respectively). Kaplan-Meier analysis
      also showed lower cumulative survival. (p [log-rank] = 0.002). In multivariate
      Cox regression analysis; undergoing coronary angiography, infection (HR 1.96, 95%
      CI 1.15-3.34, p = 0.01), left ventricular ejection fraction and maximum C
      reactive protein levels were found as independent predictors of long-term
      survival. CONCLUSION: Infection in octogenarians who were admitted due to acute
      coronary syndrome was frequent and increased their mortality substantially.

PMID- 29455061
TI  - Relationship between nurse staffing level and adult nursing-sensitive outcomes in
      tertiary hospitals of Korea: Retrospective observational study.
AB  - BACKGROUND: Nurse staffing level is an important factor on nursing sensitive
      outcome. The relationships of nurse staffing level with nursing sensitive
      outcomes such as mortality, upper gastrointestinal bleeding and pressure ulcer
      have been explored in the United States, Canada, Australia, and New Zealand.
      Lower level of hospital nurse staffing seems associated with more adverse
      outcomes, especially mortality. However, there is insufficient evidence of the
      nurse staffing level-outcome relationship in other indicators. OBJECTIVES: This
      study was conducted to describe the status and prove the relationships of nurse
      staffing level with nursing sensitive outcome indicators for adult medical and
      surgical inpatients in Korea. Patient and hospital characteristics as covariates
      on nurse sensitive outcome were also explored. DESIGN: This was a retrospective
      observational study. SETTING: The study setting was all 46 tertiary hospitals in
      Korea. PARTICIPANTS: We selected all anonymized patients aged 19 years or older
      and admitted at tertiary hospitals for two years (2013-2014) using electronic
      reimbursement claims data. METHOD: Multiple logistic regression was used to
      examine relationships of nurse staffing level (accounted for full-time registered
      nurses in general ward only) with Nursing-sensitive outcomes (NSOs) adjusted for
      patient and hospital characteristics. NSOs included urinary tract infection,
      upper gastrointestinal tract bleeding, deep vein thrombosis, hospital-acquired
      pneumonia, pressure ulcer, sepsis, shock/cardiac arrest, CNS complication, in
      hospital death, wound infection, physiologic/metabolic derangement and pulmonary
      failure. RESULTS: The total number of patients in 46 tertiary hospitals in Korea
      for two years was 3,665,307. Among these, number of patients who had at least one
      nursing-sensitive outcome was 338,369 (9.23%). The significant relationships of
      nurse staffing level with six nursing-sensitive outcome rates (urinary tract
      infection, upper gastrointestinal tract bleeding, hospital-acquired pneumonia,
      shock/cardiac arrest, in-hospital death, and wound infection) were shown. These
      six nursing-sensitive outcomes showed an increasing trend as nurse staffing level
      degraded even after adjusting for patient and hospital characteristics. When the
      nursing-sensitive outcomes between those of group 1 (bed-to-nurse ratio < 2:1)
      and group 3 (between 2.5:1 and 3:1) were compared, the adjusted incidence rate of
      shock/cardiac arrest showed the highest difference (1.06%). CONCLUSION: We
      demonstrated strong evidence for the relationships of nurse staffing level with
      six nursing-sensitive outcomes. We can use this study to improve nursing quality
      and to inform patients of the nursing quality of hospitals so they can choose
      hospitals with better nursing quality. The nurse staffing level should be
      optimized for better outcomes.

PMID- 29455062
TI  - Enhanced contraception of canine zona pellucida 3 DNA vaccine via targeting DEC
      205 in mice.
AB  - Zona pellucida 3 (ZP3) is a potential antigen for the development of
      contraceptive vaccines to control animal population. In this study, we designed a
      canine ZP3 (CZP3) DNA vaccine through targeting DEC-205 (named as pcD-scFv-CZP3c)
      and investigated its contraceptive effect in mice. Female BALB/c mice were
      intramuscularly immunized 3 times at 2 weeks intervals. After immunization,
      humoral and cellular immune responses were detected by ELISA and flow cytometry.
      The results showed that pcD-CZP3 and pcD-scFv-CZP3c induced CZP3-specific
      antibody (Ab) responses both in serum and vaginal secretions compared to
      pcDNA3.1. Additionally, compared to pcD-CZP3, pcD-scFv-CZP3c increased the levels
      of CZP3-specific Abs after a third immunization. Abs induced by these two DNA
      vaccines could bind with mice and dogs oocytes. Moreover, pcD-scFv-CZP3c enhanced
      the activation of CD4+ T cells characterized by the increased frequencies of
      CD4+CD44+ T cells. Finally, the contraceptive effect was evaluated in the
      immunized mice. These two DNA vaccines significantly decreased a mean litter size
      of mice compared to pcDNA3.1, but pcD-scFv-CZP3c group showed the smallest mean
      litter size. The mean litter size of pcD-scFv-CZP3 were 3.2 +/- 0.742 and 4.6 +/-
      1.118 in two mating tests, which were significantly lower than pcDNA3.1(P < 0.001
      and P < 0.05). Our results suggest that the CZP3 DNA vaccine targeted with DEC
      205 may be a potential strategy for developing a contraceptive DNA vaccine.

PMID- 29455063
TI  - An alanine residue in human parainfluenza virus type 3 phosphoprotein is critical
      for restricting excessive N0-P interaction and maintaining N solubility.
AB  - The phosphoprotein (P) of human parainfluenza virus type 3 (HPIV3) plays a
      pivotal role in viral RNA synthesis, which interacts with the nucleoprotein (N)
      to form a soluble N0-P complex (N0, free of RNAs) to prevent the nonspecific RNA
      binding and illegitimate aggregation of N. Functional regions within P have been
      studied intensively. However, the precise site (s) within P directly involved in
      N0-P interaction still remains unclear. In this study, using a series of deleted
      and truncated mutants of P of HPIV3, we demonstrate that amino-terminal 40 amino
      acids (aa) of P restrict and regulate N0-P interaction. Furthermore, using in
      vivo HPIV3 minigenome replicon assay, we identify a critical P mutant (PA28P)
      located in amino-terminal 40 aa, which fails to support RNA synthesis of HPIV3
      minigenome replicon. Although PA28P maintains an enhanced N-P interaction, it is
      unable to form N0-P complex and keep N soluble, thus, resulting in aggregation
      and functional abolishment of N-P complex. Moreover, we found that recombinant
      HPIV3 with mutation of A28P in P failed to be rescued. Taken together, we
      identified a residue within the extreme amino-terminus of P, which plays a
      critical role in restricting the excessively N-P interaction and keeping a
      functional N0-P complex formation.

PMID- 29455064
TI  - The dynamics of both filamentous and globular mammalian reovirus viral factories
      rely on the microtubule network.
AB  - Mammalian reovirus viral factories (VFs) form filamentous or globular structures
      depending on the viral strain. In this study, we attempt to characterize the
      dynamics of both filamentous and globular VFs. Here, we present evidence
      demonstrating that globular VFs are dynamic entities coalescing between them,
      thereby gaining in size and concomitantly decreasing in numbers during the course
      of the infection. Additionally, both kinds of VFs condense into a perinuclear
      position. Our results show that globular VFs rely on an intact MT-network for
      dynamic motion, structural assembly, and maintenance and for perinuclear
      condensation. Interestingly, dynein localizes in both kinds of VFs, having a role
      at least in large globular VFs formation. To study filamentous VF dynamics, we
      used different transfection ratios of uNS with filamentous u2. We found a MT
      network dependency for VF-like structures perinuclear condensation. Also, uNS
      promotes VFLSs perinuclear positioning as well as an increase in acetylated
      tubulin levels.

PMID- 29455065
TI  - Foot-and-mouth disease virus type O specific mutations determine RNA-dependent
      RNA polymerase fidelity and virus attenuation.
AB  - Previous studies have shown that the FMDV Asia1/YS/CHA/05 high-fidelity mutagen
      resistant variants are attenuated (Zeng et al., 2014). Here, we introduced the
      same single or multiple-amino-acid substitutions responsible for increased 3Dpol
      fidelity of type Asia1 FMDV into the type O FMDV O/YS/CHA/05 infectious clone.
      The rescued viruses O-DA and O-DAMM are lower replication fidelity mutants and
      showed an attenuated phenotype. These results demonstrated that the same amino
      acid substitution of 3Dpol in different serotypes of FMDV strains had different
      effects on viral fidelity. In addition, nucleoside analogues were used to select
      high-fidelity mutagen-resistant type O FMDV variants. The rescued mutagen
      resistant type O FMDV high-fidelity variants exhibited significantly attenuated
      fitness and a reduced virulence phenotype. These results have important
      implications for understanding the molecular mechanism of FMDV evolution and
      pathogenicity, especially in developing a safer modified live-attenuated vaccine
      against FMDV.

PMID- 29455067
TI  - Gap-enhanced Raman tags for high-contrast sentinel lymph node imaging.
AB  - The sentinel lymph node (SLN) biopsy is gaining in popularity as a procedure to
      investigate the lymphatic metastasis of malignant tumors. The commonly used
      techniques to identify the SLNs in clinical practice are blue dyes-guided
      visualization, radioisotope-based detection and near-infrared fluorescence
      imaging. However, all these methods have not been found to perfectly fit the
      clinical criteria with issues such as short retention time in SLN, poor spatial
      resolution, autofluorescence, low photostability and high cost. In this study, we
      have reported a new type of nanoprobes, named, gap-enhanced Raman tags (GERTs)
      for the SLN Raman imaging. With the advantageous features including unique
      "fingerprint" Raman signal, strong Raman enhancement, high photostability, good
      biocompatibility and extra-long retention time, we have demonstrated that GERTs
      are greatly favorable for high-contrast and deep SLN Raman imaging, which
      meanwhile reveals the dynamic migration behavior of the probes entering the SLN.
      In addition, a quantitative volumetric Raman imaging (qVRI) data-processing
      method is employed to acquire a high-resolution 3-dimensional (3D) margin of SLN
      as well as the content variation of GERTs in the SLN. Moreover, SLN detection
      could be realized via a cost-effective commercial portable Raman scanner.
      Therefore, GERTs hold the great potential to be translated in clinical
      application for accurate and intraoperative location of the SLN.

PMID- 29455066
TI  - AAV8 virions hijack serum proteins to increase hepatocyte binding for
      transduction enhancement.
AB  - It has been demonstrated that human serum albumin (HSA) directly interacts with
      AAV virions and enhances AAV transduction. Several other proteins have also been
      identified a potential for enhancing AAV8 liver transduction. In our study, LDL
      or transferrin could enhance transduction in vitro and in vivo. We also found
      that any combination of two or three of these proteins (HSA, LDL, and
      transferrin) increased AAV8 transduction in Huh7 cells and in mice liver, which
      was similar to albumin alone. Pre-incubation of HSA with AAV8 virions prevented
      AAV8 virions from binding to other proteins. Furthermore, these serum protein
      receptors didn't impact AAV8 transduction but blocked the transduction
      enhancement from AAV8-serum protein complexes. These results indicate that serum
      proteins are hijacked by AAV8 vectors to increase hepatocyte binding, which
      shares same binding site. Importantly, the results could help us design an
      optimal formulation for effective AAV vector delivery in future clinical trials.

PMID- 29455068
TI  - Corrigendum to "Versatile preparation of intracellular-acidity-sensitive oxime
      linked polysaccharide-doxorubicin conjugate for malignancy therapeutic"
      [Biomaterials 54 (2015) 72-86].

PMID- 29455069
TI  - Photo-crosslinkable, injectable sericin hydrogel as 3D biomimetic extracellular
      matrix for minimally invasive repairing cartilage.
AB  - Millions of patients worldwide suffer from cartilage injury and age/disease
      related cartilage degeneration. However, cartilage, such as articular cartilage,
      is poor at self-regeneration. Current treatments are often invasive with limited
      efficacy. Developing minimal invasive strategies for effective cartilage repair
      is highly desired. Here, we report an injectable, photo-crosslinkable sericin
      hydrogel as a biomimetic extracellular matrix for minimal invasively repairing
      cartilage. Sericin was functionalized to be sericin methacryloyl (SerMA), which
      formed an in situ hydrogel upon UV light irradiation via photo-crosslinking.
      Possessing excellent biocompatibility, SerMA hydrogels were adhesive to
      chondrocytes, and promoted the proliferation of attached chondrocytes even in a
      nutrition-lacking condition. SerMA hydrogels exhibited photoluminescent property
      allowing real-time monitoring hydrogels' status. The mechanical properties and
      degradation rates (73% for SMH-1, 47% for SMH-2 and 37% for SMH-3 after 45 days)
      of SerMA hydrogels were readily tunable by varying methacryloyl modification
      degrees to meet various repair requirements. Notably, the in vivo implantation of
      chondrocyte-laden SerMA hydrogels effectively formed artificial cartilages after
      8 weeks. Most importantly, the artificial cartilages molecularly resembled native
      cartilage as evidenced by high accumulation of cartilage-specific ECM components
      and upregulated expression of cartilage-critical genes. Together, this sericin
      hydrogel is a promising tissue engineering scaffold for generating artificial
      cartilage in vivo towards effective, minimal invasive cartilage repair.

PMID- 29455070
TI  - Oral engineered Bifidobacterium longum expressing rhMnSOD to suppress
      experimental colitis.
AB  - In recent years, using genetic engineering and bioengineering techniques,
      Bifidobacterium as a carrier to express specific functions of the protein or
      polypeptide, has become a new treatment for disease. Ulcerative colitis (UC) is a
      type of inflammatory bowel diseases (IBD). Although the cause of this
      inflammatory disorder is still unknown, a large amount of evidence suggests that
      ulcerative colitis is associated with increased activity of reactive oxygen
      species (ROS), manganese superoxide dismutase (MnSOD) is a kind of superoxide
      dismutase (SOD) has been demonstrated to play a key role in the pathophysiology
      of colitis. Here, we explored the Bifidobacterium as a drug delivery system to
      orally deliver a potent anti-inflammatory but poor penetration and stability
      antioxidant enzymes human MnSOD, transported into cells by a penetratin PEP-1. We
      constructed an expression vector expressing PEP-1-hMnSOD fusion protein, and
      successfully expressed hMnSOD fusion protein in engineered Bifidobacterium. Then
      we identified the bioactivity of engineered Bifidobacterium in LPS-induced
      inflammatory cell model. Finally, we used Bifidobacterium expressing PEP-1-hMnSOD
      fusion protein against DSS-induced ulcerative colitis mice. B. longum-PEP-1
      rhMnSOD can successfully express rhMnSOD in the colon. We found that levels of
      inflammatory cytokines TNF-alpha, IL-1beta, IL-6 and IL-8 as well as histological
      damage in colonic tissues showed that engineered Bifidobacterium effectively
      reduced dextran sulfate sodium(DSS)-induced ulcerative colitis, we also tested
      the MPO, verified the above conclusions. These results suggest that oral
      Bifidobacterium expressing PEP-1-hMnSOD fusion protein can be treated as a new
      method of UC treatment.

PMID- 29455071
TI  - The use of satellite data to measure ultraviolet-B penetrance and its potential
      association with age of multiple sclerosis onset.
AB  - BACKGROUND: Studies have indicated an association between low Ultraviolet B (UVB)
      exposure and an increased risk of developing multiple sclerosis (MS). Few
      studies, however, have explored whether UVB exposure is associated with the age
      at MS symptom onset. OBJECTIVE: We investigated the potential association between
      cumulative early life ambient UVB exposure and age at MS onset, using satellite
      data to measure ambient UVB exposure. METHODS: Adult onset MS patients were
      selected from the University of British Columbia's MS genetic database (1980
      2005). Patients' places of residence from birth to age 18 years were geocoded
      (latitude and longitude) and assigned UVB values using NASA's Total Ozone Mapping
      Spectrometer (TOMS) dataset. Linear regression was used to explore the
      relationship between cumulative UVB exposure (measured for age periods 0-6, 7-12,
      13-18, 0-12, and 0-18) and age at MS onset. RESULTS: 3226 patients were included
      in the analysis. Of these, 74% were female, with an overall mean symptom onset
      age of 33.3 years. At onset, a total of 2944 (91%) had a relapsing-remitting
      disease course, 254 (8%) had primary progressive and the disease course for 28
      (1%) was unknown. No significant associations between cumulative early life
      ambient UVB exposure and age at MS onset were observed. Patient sex, MS
      phenotype, and immigration to Canada after age 18 were significantly associated
      with age of onset (p < 0.01). CONCLUSIONS: Early life ambient UVB, as measured by
      satellite imagery, was not significantly associated with the age at MS onset.

PMID- 29455072
TI  - Pharmacophore mapping based virtual screening, molecular docking and ADMET
      studies of ROCK II inhibitors.

PMID- 29455073
TI  - Dimethyl fumarate in a patient with multiple sclerosis and type 1 diabetes
      mellitus: The importance of ketonuria.
AB  - BACKGROUND: Dimethyl fumarate (DMF) is approved for use in patients with
      relapsing-remitting multiple sclerosis (MS). Its mechanism of action is still not
      well understood, but besides the immunological pathways in MS, it may also affect
      the metabolism of normally functioning internal organs, tissues and cells. CASE
      PRESENTATION: We report on the case of 29-year-old woman with satisfactorily
      controlled type 1 diabetes (T1D), who was diagnosed as having MS. After
      administration of DMF she experienced intense, adverse gastro-intestinal
      reactions together with ketonuria up to 160 mg/dL. The highest ketone
      concentrations in the urine were observed approximately 2 h after each DMF dose
      and always with co-existing adverse reactions. Dose reduction did not improve
      symptoms and treatment had to be stopped. Twelve hours after the last dose of DMF
      all laboratory results returned to normal ranges and all gastro-intestinal
      adverse reactions were resolved within the following 24 h. CONCLUSION: This is a
      first report of ketonuria in a MS-patient with T1D treated with DMF. Patients
      with MS and co-existing metabolic diseases, which are not contraindicated for DMF
      treatment, represent a unique opportunity to address questions regarding the
      possible mechanisms of action of DMF on the cellular metabolism. The use of DMF
      in patients with metabolic diseases needs closer attention.

PMID- 29455074
TI  - The interplay of multiple sclerosis and menstrual cycle: Which one affects the
      other one?
AB  - BACKGROUND: Menstruation is suggested to affect multiple sclerosis (MS) symptoms,
      while the effect of MS on menstruation is not studied before. Here, we aimed to
      compare the pattern of menstrual cycle and its symptoms between MS patients and
      healthy controls. METHODS: This is a cross-sectional study conducted during 2015
      2016 in MS clinic of Kashani hospital, Isfahan, Iran. We included female patients
      > 14 years with diagnosis of relapsing-remitting MS, and healthy subjects as the
      control group. We collected data regarding menarche age, menstrual
      characteristics, history of premenstrual syndrome, the amount of menstrual
      bleeding, and the possible perimenstrual symptoms from all subjects. Also, MS
      patients were asked to report changes in menstrual characteristics after MS
      occurrence. RESULTS: The final study population contained 181 MS patients and 202
      healthy subjects. The mean age in MS and control group were 36.04 +/- 9.86 and
      35.16 +/- 11.30, respectively (P-value = 0.426). Menarche age in MS patients and
      control group were not statistically different (13.59 +/- 1.87 and 13.29 +/-
      1.53, respectively; P-value = 0.087). Changing menstrual characteristics was
      reported in 70 MS patients (38.7%). Irregular menstrual cycle increased from 21%
      to 40.3% after occurrence of MS (P-value < 0.001) and was reported 24.7% in the
      control group. MS patients versus controls reported more symptoms before, during,
      and after their menstrual period (P-values < 0.001). CONCLUSION: We found no
      difference regarding menstrual characteristics in MS patients before onset of the
      disease and healthy controls. Irregular menstrual cycle was observed more after
      the disease occurrence while other menstrual characteristics did not change.
      Moreover, MS patients reported many more perimenstrual symptoms.

PMID- 29455075
TI  - Prevalence of multiple sclerosis in Poland.
AB  - OBJECTIVE: The prevalence of multiple sclerosis (MS)was previously unknown in
      Poland. The aim of this study was to determine the prevalence of MS in Poland.
      METHODS: MS prevalence was determined on the basis of data from the
      Swietokrzyskie (central Poland) and Podlaskie (northeastern Poland) Voivodeships.
      The area population on the prevalence study day (December 31, 2013) was 1,268,239
      (649,007 women; 619,232 men) in central and 1,195,625 (612,979 women; 582,646
      men) in northeastern Poland. RESULTS: The overall crude prevalence rate of
      confirmed MS patients was 109.1/100,000 (95% confidence interval[CI]103.5-115.0)
      in the Swietokrzyskie and 108.7/100,000 (95% CI 103.0-114.7) in the Podlaskie
      Voivodeships. A significantly higher prevalence was recorded in females
      (149.8/100,000, 95% CI 140.6-159.3 vs. 142.4/100,000, 95% CI 133.3-152.0) than in
      males (66.5/100,000, 95% CI 60.4-73.1 vs.57.8/100,000, 95% CI 52.0-64.2)(p <
      0.001). Age-adjusted rates for the Polish Standard Population were the same in
      both regions (110.3/100,000 (95% CI 104.6-116.1) vs.110.9/100,000 (95% CI 105.1
      117.1)) and for the European Standard Population did not different statistically
      between both voivodeships (103.9/100,000 (95% CI 98.6-109.5) vs.108.5/100,000
      (95% CI 102.7-114.5)). CONCLUSION: This is the first data that obtained the level
      of MS prevalence in Poland and confirmed that Poland is a high-risk area for
      multiple sclerosis.

PMID- 29455076
TI  - From child autistic symptoms to parental affective symptoms: A family process
      model.
AB  - BACKGROUND: Depression and anxiety are prevalent among parents of children with
      autism spectrum disorder (ASD), but limited research has investigated why
      parenting a child with ASD is associated with elevated distress and increased
      risks of mental health problems. We responded to this gap in the literature by
      examining the associations between child autistic symptoms and parental affective
      symptoms, as well as the potential underlying mechanisms. Guided by a family
      process theory, we hypothesized that child autistic symptoms would be positively
      associated with parental depressive and anxiety symptoms, and that these
      associations would be mediated by parents' concerns about their children's
      characteristics (future-related worry), parental roles (parenting stress),
      marital relationships (marital conflicts), and family conditions (family economic
      pressure). METHODS: Cross-sectional questionnaire data were collected from 375
      parents of children with ASD residing in Hong Kong, China. The hypotheses were
      tested using structural equation modeling. RESULTS: Child autistic symptoms were
      positively associated with parental depressive and anxiety symptoms. These
      associations were mediated by future-related worry, parenting stress, marital
      conflicts, and family economic pressure. CONCLUSIONS: Our findings revealed the
      potential pathways through which child autism symptomatology may adversely affect
      parental mental health. Our findings also highlighted the importance of designing
      multipronged intervention programs for families raising children with ASD in
      order to improve relevant family processes and reduce parental affective
      symptoms.

PMID- 29455077
TI  - Raman studies of the interactions of fibrous carbon nanomaterials with albumin.
AB  - Adsorption or immobilization of proteins on synthetic surfaces is a key issue in
      the context of the biocompatibility of implant materials, especially those
      intended for the needs of cardiac surgery but also for the construction of
      biosensors or nanomaterials used as drug carriers. The subject of research was
      the analysis of Raman spectra of two types of fibrous carbon nanomaterials, of
      great potential for biomedical applications, incubated with human serum albumin
      (HSA). The first nanomaterial has been created on the layer of MWCNTs deposited
      by electrophoretic method (EPD) and then covered by thin film of pyrolytic carbon
      introduced by chemical vapor deposition process (CVD). The second material was
      formed from carbonized nanofibers prepared via electrospinning (ESCNFs) of
      polyacrylonitrile (PAN) precursor and then covered with pyrolytic carbon (CVD).
      The G-band blue-shift towards the position of about 1600cm-1, observed for both
      studied surfaces, clearly indicates the albumin (HSA) adhesion to the surface.
      The G and G' (2D) peak shift was employed to assess the stress build up on the
      carbon nanomaterials. The surface nano- and micro-topography as well as the
      method of ordering the carbon nanomaterial has a significant influence on the
      mode of surface-protein interaction.

PMID- 29455078
TI  - A supersensitive silver nanoprobe based aptasensor for low cost detection of
      malathion residues in water and food samples.
AB  - In the present study, we report a highly sensitive, rapid and low cost
      colorimetric monitoring of malathion (an organophosphate insecticide) employing a
      basic hexapeptide, malathion specific aptamer (oligonucleotide) and silver
      nanoparticles (AgNPs) as a nanoprobe. AgNPs are made to interact with the aptamer
      and peptide to give different optical responses depending upon the presence or
      absence of malathion. The nanoparticles remain yellow in color in the absence of
      malathion owing to the binding of aptamer with peptide which otherwise tends to
      aggregate the particles because of charge based interactions. In the presence of
      malathion, the agglomeration of the particles occurs which turns the solution
      orange. Furthermore, the developed aptasensor was successfully applied to detect
      malathion in various water samples and apple. The detection offered high
      recoveries in the range of 89-120% with the relative standard deviation within
      2.98-4.78%. The proposed methodology exhibited excellent selectivity and a very
      low limit of detection i.e. 0.5pM was achieved. The developed facile, rapid and
      low cost silver nanoprobe based on aptamer and peptide proved to be potentially
      applicable for highly selective and sensitive colorimetric sensing of trace
      levels of malathion in complex environmental samples.

PMID- 29455079
TI  - Automatic detection and segmentation of brain metastases on multimodal MR images
      with a deep convolutional neural network.
AB  - Stereotactic treatments are today the reference techniques for the irradiation of
      brain metastases in radiotherapy. The dose per fraction is very high, and
      delivered in small volumes (diameter <1 cm). As part of these treatments,
      effective detection and precise segmentation of lesions are imperative. Many
      methods based on deep-learning approaches have been developed for the automatic
      segmentation of gliomas, but very little for that of brain metastases. We adapted
      an existing 3D convolutional neural network (DeepMedic) to detect and segment
      brain metastases on MRI. At first, we sought to adapt the network parameters to
      brain metastases. We then explored the single or combined use of different MRI
      modalities, by evaluating network performance in terms of detection and
      segmentation. We also studied the interest of increasing the database with
      virtual patients or of using an additional database in which the active parts of
      the metastases are separated from the necrotic parts. Our results indicated that
      a deep network approach is promising for the detection and the segmentation of
      brain metastases on multimodal MRI.

PMID- 29455080
TI  - Optimized multi-level elongated quinary patterns for the assessment of thyroid
      nodules in ultrasound images.
AB  - Ultrasound imaging is one of the most common visualizing tools used by
      radiologists to identify the location of thyroid nodules. However, visual
      assessment of nodules is difficult and often affected by inter- and intra
      observer variabilities. Thus, a computer-aided diagnosis (CAD) system can be
      helpful to cross-verify the severity of nodules. This paper proposes a new CAD
      system to characterize thyroid nodules using optimized multi-level elongated
      quinary patterns. In this study, higher order spectral (HOS) entropy features
      extracted from these patterns appropriately distinguished benign and malignant
      nodules under particle swarm optimization (PSO) and support vector machine (SVM)
      frameworks. Our CAD algorithm achieved a maximum accuracy of 97.71% and 97.01% in
      private and public datasets respectively. The evaluation of this CAD system on
      both private and public datasets confirmed its effectiveness as a secondary tool
      in assisting radiological findings.

PMID- 29455081
TI  - Quality of life and level of burden in primary caregivers of patients with
      epilepsy: Effect of neuropsychiatric comorbidity.
AB  - BACKGROUND: Few studies are focused on the quality of life (QOL) of primary
      caregivers and the effects of the clinical variables of epilepsy and patient
      psychiatric comorbidity on primary caregivers. PURPOSE: Our main objective was to
      describe QOL and level of burden (LB) in caregivers of people with epilepsy (PWE)
      at a tertiary-care hospital in Mexico City. A secondary purpose was to determine
      if LB and QOL were different between caregivers of patients with neuropsychiatric
      comorbidity and caregivers of patients without neuropsychiatric comorbidity.
      METHODS: One hundred and fifty-one caregivers of PWE were assessed with the short
      version of the World Health Organization Quality of Life (WHOQOL) scale (WHOQOL
      BREF) and the Zarit Burden Interview. Patients' clinical and demographic data,
      along with their psychiatric histories, were collected. RESULTS: One hundred and
      twelve patients had psychiatric comorbidity. The mean LB score of the caregivers
      was 26.25+/-16.28. The mean scores for the WHOQOL-BREF domains were as follows:
      physical health, 47.8+/-10.7; psychological health, 55.4+/-11.5; social
      relationships, 47.23+/-18.6; and environment, 48.7+/-11.6. The caregivers of
      patients with psychiatric comorbidity had lower scores in the domains of
      psychological health (p=0.034) and social relationships (p=0.029) compared with
      caregivers of PWE without comorbidity. On adjusted multivariate analysis,
      aggressiveness (p=0.008), age at onset of epilepsy (p=0.02), and years with
      epilepsy (p=0.01) were associated with higher caregiver LB scores; higher
      caregiver years of education were associated with better psychological health
      (p=0.002) and more years with epilepsy (p=0.03) with lower QOL scores.
      CONCLUSION: Aggressive behavior was the psychiatric comorbidity most clearly
      associated with lower QOL and higher LB. Longer duration of epilepsy was related
      to higher burden and lower QOL. More years of education of the caregiver were
      associated with better QOL. We found no significant correlation between seizure
      control and QOL or LB.

PMID- 29455082
TI  - Evaluating subjective cognitive impairment in the adult epilepsy clinic: Effects
      of depression, number of antiepileptic medications, and seizure frequency.
AB  - OBJECTIVE: Subjective cognitive complaints are a frequent concern of patients
      with epilepsy. The Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS)
      is a patient-reported scale validated to measure adverse cognitive effects of
      antiepileptic drugs (AEDs). The goals of this study were to identify predictors
      of patient-reported cognitive dysfunction and to assess the relationship between
      subjective and objective cognitive impairment. METHODS: The Cleveland Clinic
      Knowledge Program Data Registry was used to identify adult patients seen in
      outpatient epilepsy clinic from January to May 2015 and who completed the
      following scales: ABNAS for subjective cognitive impairment, Patient Health
      Questionnaire (PHQ-9) for depression, Generalized Anxiety Disorder 7-item (GAD-7)
      scale, Quality of Life in Epilepsy (QOLIE-10), and EuroQOL five dimensions
      questionnaire (EQ-5D) for health-related quality of life. Topiramate (TPM) was
      considered a high-risk medication for cognitive impairment. Patients were
      categorized into groups based on total ABNAS score: subjective cognitive
      impairment (ABNAS>15; N=270) and no subjective cognitive impairment (ABNAS<=15;
      N=400). Multivariable logistic regression models were constructed to identify
      independent predictors of subjective cognitive impairment. In a subset of
      patients who had neuropsychological testing within 6months of completing the
      ABNAS (N=60), Pearson correlations and multivariable logistic regression models,
      controlling for number of AEDs, depression, and anxiety, assessed the
      relationship between subjective cognitive impairment and objective cognitive
      performance on measures of intelligence, attention/working memory, verbal
      fluency, naming, processing speed, manual dexterity, visuomotor processing, and
      verbal memory. RESULTS: Forty percent of patients in the overall sample
      (N=270/670) reported cognitive impairment. The variables most strongly associated
      with subjective cognitive impairment were PHQ-9 score, number of AEDs, and
      seizure frequency. In the subset of patients with neuropsychological testing,
      ABNAS score was correlated with anxiety (r=0.44), depression (r=0.38), and
      attention/working memory (r=-0.31). After adjusting for depression and anxiety,
      patients who endorsed subjective cognitive impairment scored significantly lower
      on measures of nonverbal intelligence and attention/working memory, but not on
      other cognitive measures. CONCLUSIONS: Subjective cognitive impairment as
      reported on the ABNAS is most strongly associated with depressive symptomatology,
      number of AEDs, and seizure frequency, but not with most objective cognitive
      measures. Identifying these three predictors provides a clear framework to
      understand and address subjective cognitive complaints in adult patients with
      epilepsy.

PMID- 29455083
TI  - A Single Domain-Based Anti-Her2 Antibody Has Potent Antitumor Activities.
AB  - Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately
      20% to 30% of breast cancers and various other types of cancers, which plays a
      vital role in the cancer progression. Monoclonal antibodies targeting Her2 are
      now used in the clinic to treat Her2 overexpression cancer patients. However,
      relapse or resistance is frequent with the current therapies. To generate a new
      treatment avenue against Her2, we immunized and selected a specific anti-Her2
      single domain antibody C3 for further studies. The C3-Fc antibody drove antibody
      dependent cell-mediated cytotoxicity against Her2-positive tumor cells in vitro
      and resulted in potent antitumor growth in vivo. These data suggest that the C3
      Fc antibody may provide an alternative avenue for Her2-positive cancer therapy.

PMID- 29455085
TI  - Correlation of ADC With Pathological Treatment Response for Radiation Therapy of
      Pancreatic Cancer.
AB  - PURPOSE: To investigate the feasibility of using apparent diffusion coefficient
      (ADC) to assesspathological treatment response in pancreatic ductal
      adenocarcinoma (PDAC) following neoadjuvant chemoradiation (nCR).
      MATERIALS/METHODS: MRI and pathological data collected for 25patients with
      resectable and borderline resectable PDAC following nCR were retrospectively
      analyzed. Pre- and post-nCR mean ADC values in the tumors were compared using
      Wilcoxon matched pairs test. Correlation of pathological treatment response and
      ADC values was assessed using Pearson's correlation coefficient test and receiver
      operating-curve (ROC) analysis. RESULTS: The average mean and standard deviation
      (SD) of the ADC values for all the patients analyzed were significantly higher in
      post-nCR (1.667+/-0.161*10-3) compared with those prior to nCR (1.395+/-0.136*10
      3 mm2/sec), (P<0.05). The mean ADC values after nCR were significantly correlated
      with the pathological responses (r=-0.5172); P=0.02. The area under the curve
      (AUC) of the ADC values for differentiating G1, G2 and G3 pathological responses,
      using ROC analysis, was found to be 0.6310 and P=0.03. CONCLUSION: Changes of pre
      and post-treatment ADC values significantly correlated with pathological
      treatment response for PDAC patients treated with chemoradiation therapy,
      indicating that the ADC could be used to assesstreatment response for PDAC.

PMID- 29455084
TI  - NHERF1 Between Promises and Hopes: Overview on Cancer and Prospective Openings.
AB  - Na+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein, with two
      tandem PDZ domains and a carboxyl-terminal ezrin-binding (EB) region. This
      particular sticky structure is responsible for its interaction with different
      molecules to form multi-complexes that have a pivotal role in a lot of diseases.
      In particular, its involvement during carcinogenesis and cancer progression has
      been deeply analyzed in different tumors. The role of NHERF1 is not unique in
      cancer; its activity is connected to its subcellular localization. The literature
      data suggest that NHERF1 could be a new prognostic/predictive biomarker from
      breast cancer to hematological cancers. Furthermore, the high potential of this
      molecule as therapeutical target in different carcinomas is a new challenge for
      precision medicine. These evidences are part of a future view to improving
      patient clinical management, which should allow different tumor phenotypes to be
      treated with tailored therapies. This article reviews the biology of NHERF1, its
      engagement in different signal pathways and its involvement in different cancers,
      with a specific focus on breast cancer. It also considers NHERF1 potential role
      during inflammation related to most human cancers, designating new perspectives
      in the study of this "Janus-like" protein.

PMID- 29455086
TI  - Combination of Pre-Treatment DWI-Signal Intensity and S-1 Treatment: A Predictor
      of Survival in Patients with Locally Advanced Pancreatic Cancer Receiving
      Stereotactic Body Radiation Therapy and Sequential S-1.
AB  - OBJECTIVE: To identify whether the combination of pre-treatment radiological and
      clinical factors can predict the overall survival (OS) in patients with locally
      advanced pancreatic cancer (LAPC) treated with stereotactic body radiation and
      sequential S-1 (a prodrug of 5-FU combined with two modulators) therapy with
      improved accuracy compared with that of established clinical and radiologic risk
      models. METHODS: Patients admitted with LAPC underwent diffusion weighted imaging
      (DWI) scan at 3.0-T (b = 600 s/mm2). The mean signal intensity (SIb = 600) of
      region-of-interest (ROI) was measured. The Log-rank test was done for tumor
      location, biliary stent, S-1, and other treatments and the Cox regression
      analysis was done to identify independent prognostic factors for OS. Prediction
      error curves (PEC) were used to assess potential errors in prediction of
      survival. The accuracy of prediction was evaluated by Integrated Brier Score
      (IBS) and C index. RESULTS: 41 patients were included in this study. The median
      OS was 11.7 months (2.8-23.23 months). The 1-year OS was 46%. Multivariate
      analysis showed that pre-treatment SIb = 600 value and administration of S-1 were
      independent predictors for OS. The performance of pre-treatment SIb = 600 and S-1
      treatment in combination was better than that of SIb = 600 or S-1 treatment
      alone. CONCLUSION: The combination of pre-treatment SIb = 600 and S-1 treatment
      could predict the OS in patients with LAPC undergoing SBRT and sequential S-1
      therapy with improved accuracy compared with that of established clinical and
      radiologic risk models.

PMID- 29455087
TI  - Isolation and characterization of biochar-derived organic matter fractions and
      their phenanthrene sorption.
AB  - Chemical composition and pollutant sorption of biochar-derived organic matter
      fractions (BDOMs) are critical for understanding the long-term environmental
      significance of biochar. Phenanthrene (PHE) sorption by the humic acid-like (HAL)
      fractions isolated from plant straw- (PLABs) and animal manure-based (ANIBs)
      biochars, and the residue materials (RES) after HAL extraction was investigated.
      The HAL fraction comprised approximately 50% of organic carbon (OC) of the
      original biochars. Results of XPS and 13C NMR demonstrated that the biochar
      derived HAL fractions mainly consisted of aromatic clusters substituted by
      carboxylic groups. The CO2 cumulative surface area of BDOMs excluding PLAB
      derived RES fractions was obviously lower than that of corresponding biochars.
      The sorption nonlinearity of PHE by the fresh biochars was significantly stronger
      than that of the BDOM fractions, implying that the BDOM fractions were more
      chemically homogeneous. The BDOMs generally exhibited comparable or higher OC
      normalized distribution coefficients (Koc) of PHE than the original biochars. The
      PHE logKoc values of the fresh biochars correlated negatively with the micropore
      volumes due to steric hindrance effect. In contrast, a positive relationship
      between the sorption coefficients (Kd) of BDOMs and the micropore volumes was
      observed in this study, suggesting that pore filling could dominate PHE sorption
      by the BDOMs. The positive correlation between the PHE logKoc values of the HAL
      fractions and the aromatic C contents indicates that PHE sorption by the HAL
      fractions was regulated by aromatic domains. The findings of this study improve
      our knowledge of the evolution of biochar properties after application and its
      potential environmental impacts.

PMID- 29455088
TI  - Parasite susceptibility in an amphibian host is modified by salinization and
      predators.
AB  - Secondary salinization represents a global threat to freshwater ecosystems.
      Salts, such as NaCl, can be toxic to freshwater organisms and may also modify the
      outcome of species interactions (e.g. host-parasite interactions). In nature,
      hosts and their parasites are embedded in complex communities where they face
      anthropogenic and biotic (i.e. predators) stressors that influence host-parasite
      interactions. As human populations grow, considering how anthropogenic and
      natural stressors interact to shape host-parasite interactions will become
      increasingly important. We conducted two experiments investigating: (1) the
      effects of NaCl on tadpole susceptibility to trematodes and (2) whether density-
      and trait-mediated effects of a parasite-predator (i.e. damselfly) and a host
      predator (i.e. dragonfly), respectively, modify the effects of NaCl on
      susceptibility to trematode infection. In the first experiment, we exposed
      tadpoles to three concentrations of NaCl and measured parasite infection in
      tadpoles. In the second experiment, we conducted a 2 (tadpoles exposed to 0 g L-1
      NaCl vs. 1 g L-1 NaCl) x 4 (no predator, free-ranging parasite-predator
      (damselfly), non-lethal host-predator (dragonfly kairomone), and free-ranging
      parasite-predator + dragonfly kairomone) factorial experiment. In the absence of
      predators, exposure to NaCl increased parasite infection. Of the predator
      treatments, NaCl only caused an increase in parasite infection in the presence of
      the parasite-predator. However, direct consumption of trematodes caused a
      reduction in overall infection in the parasite-predator treatment. In the
      dragonfly kairomone treatment, a reduction in tadpole movement (i.e. trematode
      avoidance behavior) led to an increase in overall infection. In the parasite
      predator + dragonfly kairomone treatment, antagonistic effects of the parasite
      predator (reduction in trematode abundance) and dragonfly kairomone (reduction in
      parasite avoidance behavior) resulted in intermediate parasite infection.
      Collectively, these findings demonstrate that NaCl can increase amphibian
      susceptibility to parasites, and underscores the importance of considering
      predator-mediated interactions in understanding how contaminants influence host
      parasite interactions.

PMID- 29455089
TI  - Occurrence and transformation of veterinary antibiotics and antibiotic resistance
      genes in dairy manure treated by advanced anaerobic digestion and conventional
      treatment methods.
AB  - Manure treatment technologies are rapidly developing to minimize eutrophication
      of surrounding environments and potentially decrease the introduction of
      antibiotics and antibiotic resistant genes (ARGs) into the environment. While
      laboratory and pilot-scale manure treatment systems boast promising results,
      antibiotic and ARG removals in full-scale systems receiving continuous manure
      input have not been evaluated. The effect of treatment on ARGs is similarly
      lacking. This study examines the occurrence and transformation of sulfonamides,
      tetracyclines, tetracycline degradation products, and related ARGs throughout a
      full-scale advanced anaerobic digester (AAD) receiving continuous manure and
      antibiotic input. Manure samples were collected throughout the AAD system to
      evaluate baseline antibiotic and ARG input (raw manure), the effect of
      hygenization (post-pasteurized manure) and anaerobic digestion (post-digestion
      manure) on antibiotic and ARG levels. Antibiotics were analyzed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS), and the ARGs tet(O), tet(W),
      sul1 and sul2 were analyzed by quantitative polymerase chain reaction (Q-PCR).
      Significant reductions in the concentrations of chlortetracycline,
      oxytetracycline, tetracycline and their degradation products were observed in
      manure liquids following treatment (p < 0.001), concomitant to significant
      increases in manure solids (p < 0.001). These results suggest sorption is the
      major removal route for tetracyclines during AAD. Significant decreases in the
      epimer-to-total residue ratios for chlortetracycline and tetracycline in manure
      solids further indicate degradation is desorption-limited. Moreover, sul1 and
      sul2 copies decreased significantly (p < 0.001) following AAD in the absence of
      sulfonamide antibiotics, while tetracyclines-resistant genes remained unchanged.
      A cross-sectional study of dairy farms utilizing natural aeration and liquid
      solid separation treatments was additionally performed to compare levels of
      antibiotics and ARGs found in AAD with the levels in common manure management
      systems. The concentration of antibiotics in raw manure varied greatly between
      farms while minimal differences in ARGs were observed. However, significant (p <
      0.01) differences in the levels of antibiotics and ARGs (except tet(W)) were
      observed in the effluents from the three different manure management systems.

PMID- 29455090
TI  - Characterization of p-Coumaric acid-induced soluble and cell wall-bound phenolic
      metabolites in relation to disease resistance to Xanthomonas campestris pv.
      campestris in Chinese cabbage.
AB  - To characterize the p-coumaric acid (pCA)-induced phenolic metabolites in
      relation to the disease resistance against Xanthomonas campestris pv. campestris
      (Xcc.), the responses of soluble- and cell wall-bound flavonoid and
      hydroxycinnamic acids compounds to the pretreatment of pCA or the inhibitor of
      the 4-coumarate-CoA ligase, 3,4-(methylenedioxy) cinnamic acid (MDCA), following
      Xcc inoculation were assessed, and the resulting data were interpreted with
      regard to susceptibility to Xcc in Chinese cabbage (Brassica rapa var.
      pekinensis). At 12 days post-inoculation (DPI) with Xcc, disease symptom
      development could be distinguished by necrotic lesions, and characterized by an
      enhanced lipid peroxidation. Overall, pCA acts as a positive stimulus for an
      accumulation of hydroxycinnamic acids and flavonoids, while MDCA acts as a
      negative regulator. Pretreatment with pCA resulted in an accumulation of specific
      hydroxycinnamic acids, pCA, ferulic acid (FA), and sinapic acid (SiA) in both
      soluble and cell wall-bound forms in Xcc-inoculated leaves, while MDCA
      pretreatment decreased accumulation in a dose-dependent manner. Two flavonoid
      compounds, epigallocatechin (EGC) and epigallocatechin gallate (EGCG), showed a
      similar response to pCA and MDCA pretreatments. These results indicate that a
      lower disease symptom development in pCA-pretreated leaves was associated with a
      higher accumulation of hydroxycinnamic acids and flavonoids, and vice-versa in
      MDCA- and non-pretreated (control) leaves.

PMID- 29455091
TI  - An UPLC-MS/MS method to determine CT-707 and its two metabolites in plasma of ALK
      positive advanced non-small cell lung cancer patients.
AB  - CT-707, a mutant-selective inhibitor of an important cancer target, anaplastic
      lymphoma kinase (ALK), is designed to be a targeted therapeutic agent for non
      small cell lung cancer (NSCLC) patients harboring ALK active and crizotinib
      resistant mutations. A rapid and sensitive ultra-performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and
      validated for the determination of CT-707 and its two metabolites (M1 and M2) in
      human plasma. The samples were purified by solid phase extraction (SPE) and
      separated on a BEH C18 column (2.1 * 50 mm, 1.7 MUm). Electrospray ionization
      (ESI) in positive ion mode and multiple reactions monitoring (MRM) were used to
      monitor the ion transitions at m/z 636.4+ -> 413.3+, 594.4+ -> 494.4+, 622.5+ ->
      536.4+, respectively. The results indicated that the method had excellent
      sensitivity and selectivity. The linear range covered from 2 to 500 ng/mL for CT
      707and from 1 to 100 ng/mL for M1 and M2. Intra-run and inter-run precisions (in
      terms of %RSD) were all <15% and the accuracies (in terms of %RE) were within the
      range of +/-15%. The lower limit of quantification (LLOQ), matrix effect,
      extraction recovery, stability, dilution test and carryover test were also
      validated and satisfied with the criteria of validation. Finally, the method was
      successfully applied to a phase I clinical study of ALK-positive advanced NSCLC
      patients after an oral administration of CT-707.

PMID- 29455092
TI  - Internet pseudoscience: Testing opioid containing formulations with tampering
      potential.
AB  - Drug tampering practices, with the aim to increase availability of drug delivery
      and/or enhance drug effects, are accessible on Internet and are practiced by some
      portion of recreational drug users. Not rarely, recreational misuse may result in
      toxic and even fatal results. The aim of the present study was to assess the
      tampering risk of medicaments containing different formulations of an opioid in
      combination with paracetamol or dexketoprofen, following the procedures reported
      in dedicated forums on the web. Tablets and suppositories containing codeine,
      tramadol and oxycodone were extracted following the reported "Cold water
      extraction"; dextromethorphan was extracted from cough syrup following the
      procedure reported as "Acid/base extraction" and fentanyl was extracted from
      transdermal patches according the procedure reported in Internet. The tampered
      products and opportunely prepared calibrators in water were analysed by liquid
      chromatography coupled to tandem mass spectrometry (LC-MS/MS). The separation of
      the analytes was carried on Agilent ZORBAX Eclipse Plus C18 (RRHT 2.1 mm * 50 mm,
      1.8 MUm) by the gradient elution of 0.01% formic acid in water and 0.01% formic
      acid in methanol. Acquisition was by MRM mode considering at least two
      transitions for compound. Declared recoveries for these home-made extractions
      claimed to exceed 99% for the opioid and to complete remove paracetamol, often
      associated to liver toxicity and thus to obtain a "safer" preparation. In this
      study, the authors demonstrated that rarely the recoveries for the opioid reached
      90% and that up to 60% of the paracetamol amount remained in solution. Thus, high
      risks for health remained both for the potential lethality of the opioid content,
      but also for the sub-lethal chronic use of these mixtures, which contained still
      uncontrolled, ignored, but often important amounts of paracetamol.

PMID- 29455093
TI  - Quantitative determination of a potent geranylgeranyl diphosphate synthase
      inhibitor using LC-MS/MS: Derivatization and application.
AB  - An isomeric mixture of homogeranyl/homoneryl triazole bisphosphonates (VSW1198)
      has previously been shown to be a potent inhibitor of geranylgeranyl diphosphate
      (GGDP) synthase (GGDPS) and of therapeutic interest for the treatment of multiple
      myeloma. We have developed and validated a selective and sensitive liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for the
      simultaneous quantitation of both the E- and Z- isomers of VSW1198 in cell
      culture media, mouse plasma and tissues. VSW1198 and internal standard are
      extracted from the bio-matrices by solid-phase extraction, followed by
      derivatization using trimethylsilyldiazomethane. The chromatographic separation
      of analytes was achieved on a Phenomenex Gemini NX column (150 mm * 2.0 mm, 5 MU)
      with gradient elution using 0.1% acetic acid and methanol/acetonitrile (1:1) as
      the mobile phase at a flow rate of 0.2 mL/min. Derivatized analytes were ionized
      with an electrospray ionization source in positive multiple reaction monitoring
      (MRM) mode and quantitated using MS/MS. The MS/MS response was linear over the
      concentration range from 0.38-1500 and 0.13-500 ng/mL for the E- and Z-isomers,
      respectively. The within- and between-day precision (relative standard deviation,
      % RSD) and accuracy were within the acceptable limits per FDA guidelines. The
      validated method was used for quantitative determination of the compounds in
      preclinical studies focused on the development of VSW1198 as a novel anti-cancer
      agent.

PMID- 29455094
TI  - Emodin attenuates titanium particle-induced osteolysis and RANKL-mediated
      osteoclastogenesis through the suppression of IKK phosphorylation.
AB  - Aseptic loosening due to wear particles is a serious challenge for orthopedic
      surgeons, sabotaging the long-term success of total joint arthroplasty. The
      existing treatments for aseptic loosening are still far from satisfactory,
      necessitating more aggressive drug exploration. Here, we examined the effect of
      emodin on titanium particle-induced osteolysis and further investigated its
      underlying mechanism in vivo and in vitro. Thirty-two C57BL/6 mice were randomly
      assigned into four groups: the Sham group (sham operation with vehicle
      injection), Vehicle group (titanium particle treatment with vehicle injections),
      Low group (titanium particle treatment with injections of 10 mg/kg/day emodin)
      and High group (titanium particle treatment with injections of 50 mg/kg/day
      emodin). Micro-CT scanning and histological analysis revealed that after emodin
      injections, the inflammatory response and bone destruction were markedly
      ameliorated. TRAP staining showed that osteoclast numbers were also dramatically
      reduced. Throughout the in vitro culture period, emodin significantly decreased
      the bone resorption area, number of osteoclasts and formation of F-actin rings.
      Mechanistic studies suggested that reduced NF-kappaB signaling might be mediating
      the inhibitory effects of emodin. Collectively, our findings suggest that emodin,
      a natural product extracted from Rheum palmatum, may be developed as a promising
      candidate for the treatment of wear particle-induced osteolysis and subsequent
      aseptic loosening.

PMID- 29455095
TI  - Establishment of pancreatic microenvironment model of ER stress: Quercetin
      attenuates beta-cell apoptosis by invoking nitric oxide-cGMP signaling in
      endothelial cells.
AB  - The involvement of endoplasmic reticulum (ER) stress in endothelial dysfunction
      and diabetes-associated complications has been well documented. Inhibition of ER
      stress represents a promising therapeutic strategy to attenuate endothelial
      dysfunction in diabetes. Recent attention has focused on the development of small
      molecule inhibitors of ER stress to maintain endothelial homeostasis in diabetes.
      Here we have developed a reliable, robust co-culture system that allows a study
      on the endothelial cells and pancreatic beta-cells crosstalk under ER stress and
      validated using a known ER stress modulator, quercetin. Furthermore, sensitizing
      of endothelial cells by quercetin (25 MUM) confers protection of pancreatic beta
      cells against ER stress through nitric oxide (NO?) signaling. In addition,
      increased intracellular insulin and NO?-mediated cyclic 3',5'-guanosine
      monophosphate (cGMP) levels in pancreatic beta-cells further confirmed the
      mechanism of protection under co-culture system. In addition, the potential
      protein targets of quercetin against ER stress in the endothelial cells were
      investigated through proteomic profiling and its phosphoprotein targets through
      Bioplex analysis. On the whole, the developed in vitro co-culture set up can
      serve as a platform to study the signaling network between the endothelial and
      pancreatic beta-cells as well as provides a mechanistic insight for the
      validation of novel ER stress modulators.

PMID- 29455096
TI  - Total inorganic nitrogen removal during the partial/complete nitrification for
      treating domestic wastewater: Removal pathways and main influencing factors.
AB  - Achieving nitrite accumulation was considered as the prerequisite of ANAMMOX,
      which hindered the application of ANAMMOX. In this study, total inorganic
      nitrogen (TIN) removal during the partial/complete nitrification was studied in a
      lab-scale sequencing batch reactor (SBR) for treating domestic wastewater. The
      results showed TIN was removed by denitrification, ANAMMOX and N2O emission
      during the partial/complete nitrification. AOB, AOA, Nitrobacter (NB), Nitrospira
      (NS), AnAOB and DNB were coexisted in the partial/complete nitrification. The
      microbial competition among these functional communities determined the type of
      nitrification, TIN removal and pathways. Since low DO concentrations benefits
      Nitrospira growth, the partial nitrification was damaged. After long-term
      operation, AOB gradually accommodated the low DO concentration. When Vmax,AOB
      (the maximum specific reaction rate of AOB) higher than Vmax,NOB (the maximum
      specific reaction rate of NOB), a part of nitrite was reduced by DNB and AnAOB.
      Therefore, TIN was removed during the complete nitrification.

PMID- 29455097
TI  - Development and application of a continuous fast microwave pyrolysis system for
      sewage sludge utilization.
AB  - A continuous fast microwave-assisted pyrolysis system was designed, fabricated,
      and tested with sewage sludge. The system is equipped with continuous biomass
      feeding, mixing of biomass and microwave absorbent, and separated catalyst
      upgrading. The effect of the sludge pyrolysis temperature (450, 500, 550, and 600
      degrees C) on the products yield, distribution and potentially energy recovery
      were investigated. The physical, chemical, and energetic properties of the raw
      sewage sludge and bio-oil, char and gas products obtained were analyzed using
      elemental analyzer, GC-MS, Micro-GC, SEM and ICP-OES. While the maximum bio-oil
      yield of 41.39 wt% was obtained at pyrolysis temperature of 550  degrees C, the
      optimal pyrolysis temperature for maximum overall energy recovery was 500 
      degrees C. The absence of carrier gas in the process may be responsible for the
      high HHV of gas products. This work could provide technical support for microwave
      assisted system scale-up and sewage sludge utilization.

PMID- 29455098
TI  - Investigations in sonication-induced intensification of crude glycerol
      fermentation to dihydroxyacetone by free and immobilized Gluconobacter oxydans.
AB  - This study reports crude glycerol fermentation by G. oxydans for dihydroxyacetone
      (DHA) production, and intensification of fermentation with sonication.
      Fermentation was carried out using both free and immobilized cells (on
      polyurethane foam support) for initial glycerol concentrations of 20, 30 and 50
      g/L. Sonication at 20% duty cycle enhanced glycerol consumption by 60-84% with no
      significant change in cell morphology. Lesser DHA yield in crude glycerol
      fermentation was attributed to possible formation of inhibitory products. Slight
      reduction in DHA yield for initial glycerol concentration of 50 g/L was
      attributed to substrate inhibition. Higher DHA productivity was obtained for
      immobilized cells. Circular dichroism analysis of intracellular proteins obtained
      from ultrasound-treated G. oxydans revealed significant reduction in alpha-helix
      and beta-sheet content. These conformational changes in protein structure could
      augment activity of intracellular glycerol dehydrogenase, which is manifested in
      terms of enhanced metabolism of glycerol by G. oxydans.

PMID- 29455099
TI  - Largely enhanced bioethanol production through the combined use of lignin
      modified sugarcane and xylose fermenting yeast strain.
AB  - The recalcitrant structure of lignocellulosic biomass is a major barrier in
      efficient biomass-to-ethanol bioconversion processes. The combination of
      feedstock engineering via modification in the lignin synthesis pathway of
      sugarcane and co-fermentation of xylose and glucose with a recombinant xylose
      utilizing yeast strain produced 148% more ethanol compared to that of the wild
      type biomass and control strain. The lignin reduced biomass led to a
      substantially increased release of fermentable sugars (glucose and xylose). The
      engineered yeast strain efficiently co-utilized glucose and xylose for
      fermentation, elevating ethanol yields. In this study, it was experimentally
      demonstrated that the combined efforts of engineering both feedstock and
      microorganisms largely enhances the bioconversion of lignocellulosic feedstock to
      bioethanol. This strategy will significantly improve the economic feasibility of
      lignocellulosic biofuels production.

PMID- 29455100
TI  - Hypofunction of left dorsolateral prefrontal cortex in depression during verbal
      fluency task: A multi-channel near-infrared spectroscopy study.
AB  - BACKGROUND: Previous functional neuroimaging studies of depression have
      demonstrated frontotemporal dysfunction, including the dorsolateral prefrontal
      cortex, while patients perform working memory and language comprehension tasks.
      Recent near-infrared spectroscopy (NIRS) studies have shown frontotemporal
      hypofunction in depression by verbal fluency task, but the regions of impairment
      affecting respective depressive symptoms still remain unclear. We investigated
      frontotemporal function during word production task in depression with multi
      channel NIRS. Further, we aimed to clarify whether any depressive symptoms affect
      frontotemporal dysfunction. METHODS: One hundred seventy-seven major depressive
      patients and 50 healthy control volunteers participated in this study. Their
      cerebral activations were compared during verbal fluency task. RESULTS: Although
      performance was not significantly different, hypoactivation in the bilateral
      frontotemporal regions was significantly observed in depressed patients, compared
      with controls. Left lateral frontotemporal activation was significantly reduced
      in the group with mandatory symptom, which is depressed mood, or loss of interest
      or pleasure, compared with the group that still has residual depressive symptoms
      in spite MDD having been remitted. LIMITATION: the MDD group had significantly
      higher age and education level than the controls. Conclusions Our findings
      indicate hypofunction of the bilateral frontotemporal regions in depression
      during verbal fluency task. Further, hypofunction of these regions in the left
      hemisphere by this task could reflect whether the subjects recovered from
      depressed mood, or loss of interest or pleasure.

PMID- 29455101
TI  - Does pedicle screw fixation of the subaxial cervical spine provide adequate
      stabilization in a multilevel vertebral body fracture model? An in vitro
      biomechanical study.
AB  - BACKGROUND: Cervical vertebral body fractures generally are treated through an
      anterior-posterior approach. Cervical pedicle screws offer an alternative to
      circumferential fixation. This biomechanical study quantifies whether cervical
      pedicle screws alone can restore the stability of a three-column vertebral body
      fracture, making standard 360 degrees  reconstruction unnecessary. METHODS: Range
      of motion (2.0 Nm) in flexion-extension, lateral bending, and axial rotation was
      tested on 10 cadaveric specimens (five/group) at C2-T1 with a spine kinematics
      simulator. Specimens were tested for flexibility of intact when a fatigue
      protocol with instrumentation was used to evaluate construct longevity. For a C4
      6 fracture, spines were instrumented with 360 degrees  reconstruction (corpectomy
      spacer + plate + lateral mass screws) (Group 1) or cervical pedicle screw
      reconstruction (C3 and C7 only) (Group 2). FINDINGS: Results are expressed as
      percentage of intact (100%). In Group 1, 360 degrees  reconstruction resulted in
      decreased motion during flexion-extension, lateral bending, and axial rotation,
      to 21.5%, 14.1%, and 48.6%, respectively, following 18,000 cycles of flexion
      extension testing. In Group 2, cervical pedicle screw reconstruction led to
      reduced motion after cyclic flexion-extension testing, to 38.4%, 12.3%, and 51.1%
      during flexion-extension, lateral bending, and axial rotation, respectively.
      INTERPRETATION: The 360 degrees  stabilization procedure provided the greatest
      initial stability. Cervical pedicle screw reconstruction resulted in less change
      in motion following cyclic loading with less variation from specimen to specimen,
      possibly caused by loosening of the shorter lateral mass screws. Cervical pedicle
      screw stabilization may be a viable alternative to 360 degrees  reconstruction
      for restoring multilevel vertebral body fracture.

PMID- 29455102
TI  - Nickel sulfide/graphitic carbon nitride/strontium titanate (NiS/g-C3N4/SrTiO3)
      composites with significantly enhanced photocatalytic hydrogen production
      activity.
AB  - NiS/g-C3N4/SrTiO3 (NS/CN/STO) composites were prepared using a facile
      hydrothermal method. The synergistic effect of g-C3N4/SrTiO3 (CN/STO)
      heterojunction and NiS cocatalyst enhanced the photocatalytic hydrogen evolution
      activity of NS/CN/STO. A hydrogen production rate of 1722.7 MUmol h-1 g-1 was
      obtained when the 2%NiS/20%g-C3N4/SrTiO3 (2NS/20CN/STO) was used for the
      photocatalytic hydrogen evolution in the presence of methanol used as a
      sacrificial agent under UV-vis light irradiation; the photocatalytic hydrogen
      production rate of 2NS/20CN/STO is 32.8, 8.9 and 4.2 times the value of that
      obtained with pure g-C3N4, SrTiO3 and 20%g-C3N4/SrTiO3 (20CN/STO), respectively.
      Moreover, in photoelectrochemical investigations when compared with 20CN/STO,
      SrTiO3 and g-C3N4, 2NS/20CN/STO exhibited significant photocurrent enhancement.
      The heterojunction and cocatalyst in NS/CN/STO improved the charge separation
      efficiency and the lifetime of the charge carriers, leading to the enhanced
      generation of electrons for photocatalytic hydrogen production.

PMID- 29455103
TI  - Facile method to immobilize ZnO particles on glass spheres for the photocatalytic
      treatment of tannery wastewater.
AB  - In order to apply the photocatalytic processes on a real scale for the treatment
      of industrial wastewaters, the use of slurry reactors employing suspended
      photocatalysts is not suitable due to the need for an uncomfortable and expensive
      separation phase of photocatalyst. To overcome this disadvantage, the
      photocatalyst particles must be immobilized on a transparent support: our work
      proposes, for this reason, a simple and cost effective method for the deposition
      of ZnO photocatalyst on glass spheres in order to formulate a structured
      photocatalyst effective in the treatment of aqueous solutions containing various
      organic dyes, commonly used in the tannery industries and in the treatment of a
      real wastewater at high COD content (11 g/L) coming from the refining unit of the
      tanning process. In particular, ZnO was immobilized on glass spheres (ZnO/GS)
      with a simple dip coating method, starting from zinc acetate aqueous solution,
      without using complexing agent and strong basic compounds. The optimization of
      ZnO amount on glass spheres was evaluated employing Acid Blue 7 dye, as model
      pollutant. In particular, it was found that best performances in terms of
      discoloration and mineralization of the target dye were obtained using the
      photocatalyst with a ZnO loading equal to 0.19 wt% (ZnO_ac1), prepared through
      only one dip-coating step. Moreover, the ZnO_ac1 photocatalyst can be easily
      separated from the reaction mixture, maintaining excellent photocatalytic
      activity and durability even after several reuse cycles. Finally, ZnO_ac1 showed
      a high photocatalytic activity in the treatment of the real wastewater, obtaining
      a COD removal equal to 70% after 180 min of UV light irradiation.

PMID- 29455104
TI  - SiO2@LaOF:Eu3+ core-shell functional nanomaterials for sensitive visualization of
      latent fingerprints and WLED applications.
AB  - For the first time, intense red color composite of SiO2@LaOF:Eu3+ core-shell
      nanostructures (NS) were fabricated via facile solvothermal method followed by
      thermal treatment. The obtained core-shell particles display better spherical
      shape and non-agglomeration with a narrow size distribution. Photoluminescence
      (PL) emission spectra exhibits intense peaks at ~593 nm, 611 nm, 650 nm
      corresponds to 5D0 -> 7FJ (J = 0, 1 and 2) Eu3+ transitions respectively. The
      spectral intensity parameters and Eu-O ligand behaviors are estimated by means of
      Judd-Ofelt (J-O) theory. CIE co-ordinates are found to be (x = 0.63, y = 0.36)
      which is very close to standard NTSC values (x = 0.67, y = 0.33). CCT value is
      ~3475 K which is less than 5000 K, as a result this phosphor is suitable for warm
      light emitting diodes. The optimized core-shell SiO2 (coat III)@LaOF:Eu3+ (5
      mol%) was used as a fluorescent labeling marker for the visualization of latent
      fingerprints on both porous and non-porous surfaces. Obtained fingerprints are
      highly sensitive and selective also no background hindrance which enables level-I
      to level-III fingerprint ridge characteristics. Observed results indicate that
      the significant improvement in luminescence of coreshell NS can be explored as a
      sensitive functional nanopowder for advanced forensic and solid state lightning
      applications.

PMID- 29455105
TI  - Shedding light on metabotropic glutamate receptors using optogenetics and
      photopharmacology.
AB  - Metabotropic glutamate receptors (mGluRs) are a family of G protein-coupled
      receptors activated by glutamate, the main excitatory neurotransmitter of the
      mammalian central nervous system. These receptors are considered as potential
      therapeutic targets in many neurological diseases but a better understanding of
      their complex molecular dynamics and of their role in the normal and pathological
      functioning of the brain is still required. Manipulating mGluRs with high spatial
      and temporal precision holds great promise for deciphering their physiological
      and pathological functions. This article reviews several recently developed
      optogenetic and photopharmacological solutions for the optical control of mGluRs
      and their applications, from the study of the molecular dynamics of receptor
      activation to the study of their roles in vivo.

PMID- 29455108
TI  - Ureaplasma isolates differentially modulate growth factors and cell adhesion
      molecules in human neonatal and adult monocytes.
AB  - Generally regarded as commensal bacteria, the pathogenicity of Ureaplasma has
      often been considered low. Controversy remains concerning the clinical relevance
      of Ureaplasma infection in the pathogenesis of inflammation-related morbidities.
      Recently, we demonstrated Ureaplasma-driven pro-inflammatory cytokine responses
      in human monocytes in vitro. We hypothesized that Ureaplasma may induce further
      inflammatory mediators. Using qRT-PCR and multi-analyte immunoassay, we assessed
      the expression of granulocyte-colony stimulating factor (G-CSF), vascular
      endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1) and
      vascular cell adhesion molecule 1 (VCAM-1) in term neonatal and adult monocytes
      exposed to Ureaplasma urealyticum serovar 8 (Uu8) and U. parvum serovar 3 (Up3).
      Ureaplasma significantly induced VEGF mRNA in neonatal (Up3: p < 0.05, versus
      broth control) and adult monocytes (Uu8: p < 0.05) as well as ICAM-1 mRNA in
      neonatal cells (p < 0.05 each). As far as protein expression was concerned, Up3
      stimulated VEGF release in both monocyte subsets (p < 0.01) and enhanced
      secretion of ICAM-1 protein in neonatal monocytes (p < 0.05). In adult cells,
      ICAM-1 protein release was increased upon exposure to both isolates (Uu8: p <
      0.05, Up3: p < 0.01). Ureaplasma-induced responses did not significantly differ
      from corresponding levels mediated by E. coli lipopolysaccharide (LPS). The
      stimulatory effects were dose-dependent. Ureaplasma infection, on the contrary,
      did not affect G-CSF and VCAM-1 expression. Of note, co-infection of LPS-primed
      neonatal monocytes with Ureaplasma enhanced LPS-induced ICAM-1 release (Uu8: p <
      0.05). Our results confirm Ureaplasma-driven pro-inflammatory activation of human
      monocytes in vitro, demonstrating a differential modulation of growth factors and
      cell adhesion molecules, that might promote unbalanced monocyte responses and
      adverse immunomodulation.

PMID- 29455107
TI  - Helios expression in regulatory T cells promotes immunosuppression, angiogenesis
      and the growth of leukemia cells in pediatric acute lymphoblastic leukemia.
AB  - Regulatory T cells (Tregs) characterized by the transcription factor forkhead box
      P3 (FoxP3) are crucial for maintaining immune tolerance and preventing
      autoimmunity. However, FoxP3 does not function alone and Helios is considered a
      potential candidate for defining Treg subsets. In this study, we investigated the
      expression and function of Helios for identifying Tregs in childhood precursor B
      cell acute lymphoblastic leukemia (pre-B ALL). Our results demonstrated that
      patients with pre-B ALL had a higher percentage of Helios+ FoxP3+ CD4+ Tregs. And
      there was a positive correlation between the expression of Helios and the
      suppressive function of Tregs, the risk gradation of ALL. Helios in combination
      with CD4 and FoxP3 may be an effective way to detect functional Tregs in pre-B
      ALL by promoting the secretion of transforming growth factor (TGF)-beta1.
      Furthermore, Helios+ Tregs could regulate angiogenesis in the BM niche of pre-B
      ALL via the VEGFA/VEGFR2 pathway. We also found Helios+ Tregs decreased apoptosis
      rate of nalm-6 cells by up-regulating the expression of anti-apoptosis protein
      Bcl-2. In summary, these data strongly imply the physiological importance of
      Helios expression in Tregs, and suggest that the manipulation of Helios may serve
      as a novel strategy for cancer immunotherapy.

PMID- 29455106
TI  - Nonribosomal peptides for iron acquisition: pyochelin biosynthesis as a case
      study.
AB  - Microbes synthesize small, iron-chelating molecules known as siderophores to
      acquire iron from the environment. One way siderophores are generated is by
      nonribosomal peptide synthetases (NRPSs). The bioactive peptides generated by
      NRPS enzymes have unique chemical features, which are incorporated by accessory
      and tailoring domains or proteins. The first part of this review summarizes
      recent progress in NRPS structural biology. The second part uses the biosynthesis
      of pyochelin, a siderophore from Pseudomonas aeruginosa, as a case study to
      examine enzymatic methods for generating the observed diversity in NRPS-derived
      natural products.

PMID- 29455109
TI  - Dysregulation of JAK/STAT genes by vasoactive intestinal peptide (VIP) in
      Salmonella-infected monocytes may inhibit its therapeutic potential in human
      sepsis.
AB  - Murine/LPS models of Gram negative sepsis indicate that vasoactive intestinal
      peptide (VIP) has therapeutic potential. We investigated the unknown effect of
      VIP on JAK/STAT proteins and genes in human monocytes infected with Salmonella
      Typhimurium 14028. S. Typhimurium 14028 increased expression of both IL-6
      receptor (IL-6R) and interferon gamma receptor 1 (IFNgammaR1) on monocytes but co
      culture of infected monocytes with VIP (10-7 M) only decreased expression of
      IFNgammaR1 (P < 0.05). In contrast, S. Typhimurium 14028 infection or co-culture
      with VIP had no effect on IL-10 receptor expression on the monocyte surface.
      However, S. Typhimurium 14028 down regulated IFNGR1 gene expression and this was
      not altered by co-culture with VIP, suggesting that changes in IFNgammaR1 protein
      may be due to an effect on cytoplasmic transport. 15 JAK/STAT genes, out of 84
      studied, were up-regulated by S. Typhimurium 14028 infection and five were down
      regulated. Co-culture with VIP significantly decreased expression of two genes
      (IFNG and IL-20) and increased expression of three genes (SOCS1, SOCS3 and STAT4)
      (P < 0.05). S. Typhimurium 14028 also increased expression of PTPN1, which
      dephosphorylates JAK2 and TYK2. This was unaltered by co-culture with VIP but S.
      Typhimurium 14028-induced expression of ISG15, associated with susceptibility to
      Gram negative infection, was further increased by VIP. We conclude that the
      effect of VIP on JAK/STAT genes may preclude its therapeutic use in human Gram
      negative sepsis.

PMID- 29455111
TI  - DeepMitosis: Mitosis detection via deep detection, verification and segmentation
      networks.
AB  - Mitotic count is a critical predictor of tumor aggressiveness in the breast
      cancer diagnosis. Nowadays mitosis counting is mainly performed by pathologists
      manually, which is extremely arduous and time-consuming. In this paper, we
      propose an accurate method for detecting the mitotic cells from histopathological
      slides using a novel multi-stage deep learning framework. Our method consists of
      a deep segmentation network for generating mitosis region when only a weak label
      is given (i.e., only the centroid pixel of mitosis is annotated), an elaborately
      designed deep detection network for localizing mitosis by using contextual region
      information, and a deep verification network for improving detection accuracy by
      removing false positives. We validate the proposed deep learning method on two
      widely used Mitosis Detection in Breast Cancer Histological Images (MITOSIS)
      datasets. Experimental results show that we can achieve the highest F-score on
      the MITOSIS dataset from ICPR 2012 grand challenge merely using the deep
      detection network. For the ICPR 2014 MITOSIS dataset that only provides the
      centroid location of mitosis, we employ the segmentation model to estimate the
      bounding box annotation for training the deep detection network. We also apply
      the verification model to eliminate some false positives produced from the
      detection model. By fusing scores of the detection and verification models, we
      achieve the state-of-the-art results. Moreover, our method is very fast with GPU
      computing, which makes it feasible for clinical practice.

PMID- 29455110
TI  - Nipple-sparing bilateral prophylactic mastectomy and immediate reconstruction
      with TiLoop(r) Bra mesh in BRCA1/2 mutation carriers: A prospective study of long
      term and patient reported outcomes using the BREAST-Q.
AB  - BACKGROUND: Although demand for prophylactic mastectomy is increasing over time
      among women at a high risk for breast cancer, there is a paucity of studies on
      long term patient-reported outcomes after this procedure. METHODS: Between
      January 2011 and January 2015, 46 patients documented BRCA1/2 mutation carriers,
      eligible for prophylactic nipple-sparing mastectomy (NSM) and immediate breast
      prosthetic reconstruction were registered at our Institution. Patients underwent
      NSM and subcutaneous reconstruction with implant covered by a titanium-coated
      polypropylene mesh (TiLoop(r)). The BREAST-Q questionnaire was given to patients
      prior to surgery and at 1 and 2 years follow-up points. Capsular contracture was
      evaluated by Baker scale. Surgical outcomes along with the changes in BREAST-Q
      score were analyzed over time. RESULTS: Complications were reported in only one
      case and after two years the capsular contracture rates were acceptable (grade I:
      65,2%; grade II: 32,6%; grade III 2,2%). At one year and two year follow-ups
      patients reported high rates in the measures of overall satisfaction with breasts
      (72,5 and 73,7 respectively), psychosocial well-being (78,4 and 78,6), sexual
      well-being (58,8 and 59,4), physical well-being (77,6 and 80,6) and overall
      satisfaction with outcome (75,7 and 79,7). A statistically significant increase
      in all BREAST-domains from the preoperative to the postoperative period was
      reported at one and two years follow-ups (p < 0,05). CONCLUSION: Following
      bilateral prophylactic NSM and immediate subcutaneous reconstruction with
      TiLoop(r), patients demonstrated high levels of satisfaction and quality of life
      as measured by BREAST-Q. 2-years outcomes confirmed high patient comfort with
      increased scores from the preoperative baseline level.

PMID- 29455112
TI  - Shielding properties of the ordinary concrete loaded with micro- and nano
      particles against neutron and gamma radiations.
AB  - The shielding properties of ordinary concrete doped with some micro and nano
      scaled materials were studied in the current study. Narrow beam geometry was
      simulated using MCNPX Monte Carlo code and the mass attenuation coefficient of
      ordinary concrete doped with PbO2, Fe2O3, WO3 and H4B (Boronium) in both nano and
      micro scales was calculated for photon and neutron beams. Mono-energetic beams of
      neutrons (100-3000 keV) and photons (142-1250 keV) were used for calculations.
      The concrete doped with nano-sized particles showed higher neutron removal cross
      section (7%) and photon attenuation coefficient (8%) relative to micro-particles.
      Application of nano-sized material in the composition of new concretes for dual
      protection against neutrons and photons are recommended. For further studies, the
      calculation of attenuation coefficients of these nano-concretes against higher
      energies of neutrons and photons and different particles are suggested.

PMID- 29455113
TI  - Experimental study and simulation of 63Zn production via proton induce reaction.
AB  - The 63Zn was produced by16.8 MeV proton irradiation of natural copper. Thick
      target yield for 63Zn in the energy range of 16.8 ->12.2 MeV was 2.47 +/- 0.12
      GBq/MUA.h. Reasonable agreement between achieved experimental data and
      theoretical value of thick target yield for 63Zn was observed. A simple
      separation procedure of 63Zn from copper target was developed using cation
      exchange chromatography. About 88 +/- 5% of the loaded activity was recovered.
      The performance of FLUKA to reproduce experimental data of thick target yield of
      63Zn is validated. The achieved results from this code were compared with the
      corresponding experimental data. This comparison demonstrated that FLUKA provides
      a suitable tool for the simulation of radionuclide production using proton
      irradiation.

PMID- 29455114
TI  - Holistic processing in mother's face perception for infants.
AB  - In this study, we created composite faces using mothers' faces to examine
      holistic face processing in infants aged 5-8 months. The composite-face effect
      occurred only in infants aged 7-8 months, suggesting that infants older than 7
      months are able to process familiar faces holistically.

PMID- 29455115
TI  - Therapeutic use of heparin and derivatives beyond anticoagulation in patients
      with bronchial asthma or COPD.
AB  - In this review, we identify potential targets for the therapeutic effects of
      heparin in asthma and chronic obstructive pulmonary disease (COPD), consider the
      safety and delivery modalities of this therapeutic approach. Specifically, we
      point to the anti-inflammatory, antioxidant and mucolytic effects of
      unfractionated heparin with potential to modify disease progression in COPD and
      asthma when administered via the inhaled route. Inhaled heparin may represent an
      effective add-on therapy in COPD and asthma patient groups, especially when
      taking into consideration the relative deficiency in endogenous heparin reported
      in asthma patients.

PMID- 29455116
TI  - Linking mode of action of the model respiratory and photosynthesis uncoupler 3,5
      dichlorophenol to adverse outcomes in Lemna minor.
AB  - Standard chemical toxicity testing guidelines using aquatic plant Lemna minor
      have been developed by several international standardisation organisations.
      Although being highly useful for regulatory purposes by focusing on traditional
      adverse endpoints, these tests provide limited information about the toxic
      mechanisms and modes of action (MoA). The present study aimed to use selected
      functional assays in L. minor after exposure to 3,5-dichlorophenol (3,5-DCP) as a
      model to characterise the toxic mechanisms causing growth inhibition and
      lethality in primary producers. The results demonstrated that 3,5-DCP caused
      concentration-dependent effects in chloroplasts and mitochondria. Uncoupling of
      oxidative phosphorylation (OXPHOS), reduction in chlorophyll (Chlorophyll a and
      b) content, reproduction rate and frond size were the most sensitive endpoints,
      followed by formation of reactive oxygen species (ROS), lipid peroxidation (LPO),
      reduction of carotenoid content and impairment of photosynthesis efficiency.
      Suppression of photosystem II (PSII) efficiency, electron transport rate (ETR),
      chlorophyll (a and b) contents and oxidative phosphorylation (OXPHOS) were
      closely correlated while ROS production and LPO were negative correlated with
      ETR, carotenoid content and growth parameters. A network of conceptual Adverse
      Outcome Pathways (AOPs) was developed to decipher the causal relationships
      between molecular, cellular, and apical adverse effects occurring in L. minor to
      form a basis for future studies with similar compounds.

PMID- 29455117
TI  - Road traffic accidents in Scottish military veterans.
AB  - Road traffic accidents (RTA) are recognised to be an important cause of death and
      injury in serving military personnel but little is known about the risk in
      veterans. We used data from the Scottish Veterans Health Study to examine the
      risk of RTA in a large national cohort of veterans, in comparison with people who
      had never served. We conducted a retrospective cohort study of 57,000 veterans
      and 173,000 non-veterans, followed up for up to 30 years, using survival analysis
      to compare risk of RTA injury. Subgroup analysis was used to explore trends by
      birth cohort and length of service. Overall, veterans had a higher risk of RTA
      (Cox proportional hazard ratio (HR) 1.17, 95% confidence intervals (CI) 1.14
      1.20). The risk was highest in the veterans with the shortest service (early
      service leavers), including those who did not complete initial military training
      (HR 1.31, 95% CI 1.23-1.40). The mean age at first RTA was 34 years, irrespective
      of age at leaving service, and the greatest increase in risk was in veterans born
      in the 1960s, but veterans born after 1970 showed no increase in risk. We have
      therefore demonstrated that the increased risk of RTA observed in serving
      military personnel persists in veterans through the fourth decade of life. The
      high risk in early service leavers is likely to be related to risk factors other
      than military service, including previous childhood adversity. Recent Ministry of
      Defence road safety programmes may now be reducing the long-term risk of RTA
      injury.

PMID- 29455118
TI  - Multivariate dynamic Tobit models with lagged observed dependent variables: An
      effectiveness analysis of highway safety laws.
AB  - Highway safety laws aim to influence driver behaviors so as to reduce the
      frequency and severity of crashes, and their outcomes. For one specific highway
      safety law, it would have different effects on the crashes across severities.
      Understanding such effects can help policy makers upgrade current laws and hence
      improve traffic safety. To investigate the effects of highway safety laws on
      crashes across severities, multivariate models are needed to account for the
      interdependency issues in crash counts across severities. Based on the
      characteristics of the dependent variables, multivariate dynamic Tobit (MVDT)
      models are proposed to analyze crash counts that are aggregated at the state
      level. Lagged observed dependent variables are incorporated into the MVDT models
      to account for potential temporal correlation issues in crash data. The state
      highway safety law related factors are used as the explanatory variables and
      socio-demographic and traffic factors are used as the control variables. Three
      models, a MVDT model with lagged observed dependent variables, a MVDT model with
      unobserved random variables, and a multivariate static Tobit (MVST) model are
      developed and compared. The results show that among the investigated models, the
      MVDT models with lagged observed dependent variables have the best goodness-of
      fit. The findings indicate that, compared to the MVST, the MVDT models have
      better explanatory power and prediction accuracy. The MVDT model with lagged
      observed variables can better handle the stochasticity and dependency in the
      temporal evolution of the crash counts and the estimated values from the model
      are closer to the observed values. The results show that more lives could be
      saved if law enforcement agencies can make a sustained effort to educate the
      public about the importance of motorcyclists wearing helmets. Motor vehicle crash
      related deaths, injuries, and property damages could be reduced if states enact
      laws for stricter text messaging rules, higher speeding fines, older licensing
      age, and stronger graduated licensing provisions. Injury and PDO crashes would be
      significantly reduced with stricter laws prohibiting the use of hand-held
      communication devices and higher fines for drunk driving.

PMID- 29455119
TI  - Developing a safety heatmap of uncontrolled intersections using both conflict
      probability and severity.
AB  - This paper presents a method to assess the safety of uncontrolled intersections
      considering two major properties of traffic conflicts-conflict probability and
      severity. This method assesses both the safety level of the entire intersection
      in addition to the distribution of safety within it. Intersections are modeled by
      a two-dimensional Cartesian coordinate system and the internal space of
      intersections is divided into cells. First, the vehicle movement characteristics
      of an uncontrolled intersection are modeled. Second, the conflict probability of
      each cell within the intersection is estimated considering the approaching
      probability and lateral migration probability of vehicles. The quantification of
      conflict severity is based on kinetic energy loss of potential crashes. Cluster
      analysis is used to combine conflict probability and severity to model the safety
      assessment of each cell. Third, the application of the method is discussed, and
      an overall safety index of intersections is proposed which considers weighted
      safety level and relative value of areas of different safety levels. Finally, a
      case study, which includes three different designs, is presented along with
      safety heatmaps to demonstrate the results. The results not only demonstrate the
      validity of the model, but also indicate that the proposed method can be applied
      to: i) safety evaluation of build-up intersections; ii) dangerous position
      management within an intersection; iii) safety assessment of designed
      intersections, and iv) safety level comparison among different intersections or
      various designs for a single intersection. Using this method, engineers and
      planners can better evaluate and improve the safety of existing or future
      uncontrolled intersections.

PMID- 29455120
TI  - Amyand's hernia with acute gangrenous appendicitis and cecal perforation: A case
      report and review of the literature.
AB  - INTRODUCTION: An Amyand's hernia is a heterogeneous clinical condition defined by
      the presence of the vermiform appendix within an inguinal hernia sac, which may
      or may not contain other abdominal contents or pathologic inflammatory changes.
      Herein we present an exceptionally rare case of an Amyand's hernia containing
      acute appendicitis and a perforated cecum. PRESENTATION OF CASE: A 46-year-old
      male with a right inguinal hernia of 2-3 year duration presented to our Emergency
      Department complaining of acute onset abdominal and groin pain. The patient was
      diagnosed with an incarcerated right inguinal hernia and underwent emergent
      surgical repair. Intraoperatively a reactive fluid was found within the hernia
      sac that prompted an exploratory laparotomy for suspected bowel perforation. The
      hernia was then found to contain an inflamed gangrenous appendix with an inflamed
      and perforated cecum. An ileocecectomy and enteroenterostomy was performed and
      the hernia defect was repaired without mesh. DISCUSSION: With an estimated
      incidence of only 1%, Amyand's hernias are rare and lack a clear evidence-based
      management scheme. Moreover, they can contain a diverse range of pathologic
      features and presentations that can complicate diagnosis and treatment. To avoid
      potential morbidity and mortality, the surgeon must consider an Amyand's hernia
      on his or her differential when operating on inguinal hernias and be aware of the
      associated presentations, complications, and management schemes. CONCLUSION:
      There is a paucity of reports describing simultaneous appendicitis and cecal
      perforation within an Amyand's hernia. In our case, ileocecectomy and Bassini
      hernia repair with close follow-up led to a favorable outcome.

PMID- 29455121
TI  - Ozone assisted oxidation of gaseous PCDD/Fs over CNTs-containing composite
      catalysts at low temperature.
AB  - Ozone assisted carbon nanotubes (CNTs) supported vanadium oxide/titanium dioxide
      (V/Ti-CNTs) or vanadium oxide-manganese oxide/titanium dioxide (V-Mn/Ti-CNTs)
      catalysts towards gaseous PCDD/Fs (polychlorinated dibenzo-p-dioxins and
      polychlorinated dibenzofurans) catalytic oxidations at low temperature (150 
      degrees C) were investigated. The removal efficiency (RE) and decomposition
      efficiency (DE) of PCDD/Fs achieved with V-Mn/Ti-CNTs alone were 95% and 45% at
      150  degrees C under a space velocity (SV) of 14000 h-1; yet, these values
      reached 99% and 91% when catalyst and low concentration (50 ppm) ozone were used
      in combined. The ozone promotion effect on catalytic activity was further
      enhanced with the addition of manganese oxide (MnOx) and CNTs. Adding MnOx and
      CNTs in V/Ti catalysts facilitated the ozone decomposition (creating more active
      species on catalyst surface), thus, improved ozone utilization (demanding
      relatively lower ozone addition concentration). On the other hand, this study
      threw light upon ozone promotion mechanism based on the comparison of catalyst
      properties (i.e. components, surface area, surface acidity, redox ability and
      oxidation state) before and after ozone treatment. The experimental results
      indicate that a synergistic effect exists between catalyst and ozone: ozone is
      captured and decomposed on catalyst surface; meanwhile, the catalyst properties
      are changed by ozone in return. Reactive oxygen species from ozone decomposition
      and the accompanied catalyst properties optimization are crucial reasons for
      catalyst activation at low temperature.

PMID- 29455122
TI  - Benzotriazoles and benzothiazoles in paired maternal urine and amniotic fluid
      samples from Tianjin, China.
AB  - Benzotriazoles (BTRs) and benzothiazoles (BTHs) are two groups of heterocyclic
      compounds that are widely detected in the environment. In this study, the levels
      of BTRs and BTHs in 79 paired maternal urine and amniotic fluid samples from
      Tianjin were investigated. BTRs were detected in most maternal urine samples,
      with a median concentration of ?BTRs of 0.88 ng/mL. BTH was detected in all
      maternal urine samples, with a median concentration of 1.35 ng/mL. Tolyltriazole
      (TTR, i.e., the sum of 4-methyl-1H-benzotriazole and 5-methyl-1H-benzotriazole)
      and BTH were detected in amniotic fluid with detection rates (DRs) > 50% and
      median concentrations of 0.026 and 0.61 ng/mL, respectively. The median
      concentrations of ?BTRs and ?BTHs (0.026 and 0.72 ng/mL) in amniotic fluid were
      lower than those in maternal urine. The median ratio of the ?BTRs concentrations
      in amniotic fluid to those in maternal urine was 0.030, with a range of 0.017
      1.82, while the median value for TTR, BTH and 5-Cl-1H-BTR were 0.12, 0.46, and
      1.43, respectively. This indicates greater distribution in fetal excretion to 5
      Cl-1H-BTR than BTH and TTR. The concentrations of ?BTRs in maternal urine
      exhibited significant distribution differences (p < 0.05) with respect to some
      parameters, including maternal age, gestational week, gravidity, parity, and
      fetal weight. However, no significant correlations (p > 0.05) were observed in
      target compounds in amniotic fluid for the epidemiological factors assessed
      herein. The geometric means of the estimated daily intakes were 1.15 (0.052-7.66)
      MUg/day and 1.92 (0.027-6.64) MUg/day for ?BTRs and ?BTHs in present study, which
      are lower than those reported in previous study.

PMID- 29455123
TI  - Highly efficient pyrocatalysis of pyroelectric NaNbO3 shape-controllable
      nanoparticles for room-temperature dye decomposition.
AB  - In this work, pyrocatalytic effect is realized in hydrothermally-synthesized
      pyroelectric NaNbO3 shape-controllable nanoparticles via the product of
      pyroelectric effect and electrochemical redox. A pyro-catalysis is designed to
      decompose dye wastewater. Under the 23-50  degrees C heating-cooling cycle, the
      maximum pyrocatalytic decomposition ratio of NaNbO3 nanorods, nanosheets and
      nanocubes are 96%, 76% and 33%, respectively. The pyrocatalytic effect of NaNbO3
      nanoparticles is potential in developing a environmentally-friendly technology
      for room-temperature pyrocatalysis through utilizing natural heat energy.

PMID- 29455124
TI  - Combination effects of airborne particulate matter exposure and high-fat diet on
      hepatic fibrosis through regulating the ROS-endoplasmic reticulum stress
      TGFbeta/SMADs axis in mice.
AB  - BACKGROUND: Hepatic fibrosis, characterized by an excessive accumulation of
      extracellular matrix, is associated with toxic substance exposure, chronic
      infections, mechanical injury, airborne fine particulate matter (PM2.5) exposure
      and metabolic disease. This study aimed to investigate the effect and mechanism
      of long-term, real-world airborne particulate matter (PM) exposure on hepatic
      fibrosis and further explored whether combination treatment of PM exposure and
      high-fat diet (HFD) aggravate the adverse effects in mice. METHODS AND RESULTS:
      Six-week-old male C57BL/6J mice fed with either a standard chow diet (STD) or an
      HFD were treated with either filtered air (FA) or PM for 18 weeks. Metabolic
      parameters, histological examination, gene expression analysis, and Western blot
      analysis were utilized to measure the effect and mechanism of PM exposure on
      hepatic fibrosis and to further analyze the synergistic effect of HFD. Subchronic
      airborne PM exposure induces hepatic fibrosis in mice, and combination treatment
      of PM exposure and HFD accelerate the adverse effect. Meanwhile, subchronic
      exposure to real-world PM increased the level of hepatic ROS, and the expression
      of endoplasmic reticulum (ER) stress markers (GRP78 and CHOP), p-SMAD2 and p
      SMAD3, as well as up-regulated TGFbeta and collagen 1 in liver tissues.
      Furthermore, PM exposure and HFD displayed the synergistic effects on these
      changes in liver. CONCLUSION: Our findings indicate that airborne PM exposure
      aggravates HFD -induced hepatic fibrosis. The ROS-ER stress-TGFbeta/SMADs
      regulatory axis mediates the effects of airborne PM exposure on accelerating
      hepatic fibrosis.

PMID- 29455125
TI  - Trends in analytical techniques applied to particulate matter characterization: A
      critical review of fundaments and applications.
AB  - Epidemiological studies have shown the association of airborne particulate matter
      (PM) size and chemical composition with health problems affecting the
      cardiorespiratory and central nervous systems. PM also act as cloud condensation
      nuclei (CNN) or ice nuclei (IN), taking part in the clouds formation process, and
      therefore can impact the climate. There are several works using different
      analytical techniques in PM chemical and physical characterization to supply
      information to source apportionment models that help environmental agencies to
      assess damages accountability. Despite the numerous analytical techniques
      described in the literature available for PM characterization, laboratories are
      normally limited to the in-house available techniques, which raises the question
      if a given technique is suitable for the purpose of a specific experimental work.
      The aim of this work consists of summarizing the main available technologies for
      PM characterization, serving as a guide for readers to find the most appropriate
      technique(s) for their investigation. Elemental analysis techniques like atomic
      spectrometry based and X-ray based techniques, organic and carbonaceous
      techniques and surface analysis techniques are discussed, illustrating their main
      features as well as their advantages and drawbacks. We also discuss the trends in
      analytical techniques used over the last two decades. The choice among all
      techniques is a function of a number of parameters such as: the relevant
      particles physical properties, sampling and measuring time, access to available
      facilities and the costs associated to equipment acquisition, among other
      considerations. An analytical guide map is presented as a guideline for choosing
      the most appropriated technique for a given analytical information required.

PMID- 29455126
TI  - Removal mechanisms of volatile organic compounds (VOCs) from effluent of common
      effluent treatment plant (CETP).
AB  - This study investigated the occurrence, removal and influence of plant-operating
      conditions on removal mechanisms of 83 VOCs in different treatment units of a
      CETP in Mumbai, treating industrial waste on primary and secondary level. A mass
      balance approach was used to predict VOC removal by volatilization, stripping,
      weir drop, adsorption, and biodegradation. Results indicate that ~17% of VOCs
      were removed by stripping in equalization tank and ~8% were removed by weir drop
      in primary clari-flocculator respectively. Biodegradation was the dominant
      mechanism in aeration tank and was relatively poor for hydrophobic compounds
      which were more vulnerable to removal by stripping. Stripping rates could be
      reduced by increasing the active biomass concentration and using fine pore
      diffusers to reduce the air/effluent ratio. Decrease in Henry's constant and
      compound concentration can shift the main removal mechanism from stripping to
      biodegradation. Results also show considerable agreement between measured (71.2%)
      and predicted (67.1%) total removal, especially in aeration tanks. Equalization
      tanks (actual, 20.5%, predicted, 16.9%), primary clari-flocculator (actual,
      14.2%, predicted, 7.7%), and secondary clarifier units (actual, 29.5%, predicted,
      16.8%) showed fairly acceptable differences in measured and predicted removal.
      The effect of other mechanisms on VOC removal need to be further explored owing
      to their major contribution to VOC removal. This study is the first attempt in
      understanding the mechanisms behind the removal of VOCs in each treatment unit,
      especially equalization tanks and clarifier units, which have been severely
      underestimated till date.

PMID- 29455128
TI  - Source apportionment of ambient PM2.5 in two locations in central Tehran using
      the Positive Matrix Factorization (PMF) model.
AB  - In this study, the positive matrix factorization (PMF) model was used for source
      apportionment of ambient PM2.5 in two locations in the central Tehran from May
      2012 through June 2013. The average PM2.5 mass concentrations were 30.9 and
      33.2MUg/m3 in Tohid retirement home and the school dormitory, respectively.
      Metals and trace elements, water-soluble ions, and PM2.5 mass concentrations were
      used as inputs to the model. Concentrations of elemental and organic carbon (EC
      and OC), and meteorological data were also used as auxiliary variables to help
      with the factor identification and interpretation. A 7-factor solution was
      identified as the best solution for both sites. The identified source factors
      included vehicular emissions, secondary aerosol, industrial emissions, biomass
      burning, soil, and road dust (including tire and brake wear particles) in both
      sampling sites. Results indicated that almost half of PM2.5 mass can be
      attributed to vehicular emissions at both sites. Secondary aerosol was the second
      major contributor to PM2.5 mass concentrations at both sites, with contributions
      of around 25% on average for both sites. In addition, while two industrial
      factors were identified in Tohid retirement home (with an overall contribution of
      17%), only one industrial factor (with a minimal contribution of <2%) was
      identified at Tohid retirement home, probably due to the fact that the retirement
      home is impacted to a higher degree by industry-related activities. The other
      factors included biomass burning, road dust, and soil, with overall contributions
      of around 20% in both sites. Results of this study clearly indicate the major
      role of traffic-related emissions (both tailpipe and non-tailpipe) on ambient
      PM2.5 concentrations, and can be used as a beneficial tool for air quality policy
      makers to mitigate adverse health effects of exposure to PM2.5.

PMID- 29455127
TI  - Technical basis for using passive sampling as a biomimetic extraction procedure
      to assess bioavailability and predict toxicity of petroleum substances.
AB  - Solid-phase microextraction fibers coated with polydimethylsiloxane (PDMS)
      provide a convenient passive sampling format to characterize bioavailability of
      petroleum substances. Hydrocarbons absorb onto PDMS in proportion to both freely
      dissolved concentrations and partitioning properties of the individual
      constituents, which parallels the mechanistic basis used to predict aquatic
      toxicity in the PETROTOX model. When deployed in a non-depletive manner,
      combining SPME with thermal desorption and quantification using gas
      chromatography-flame ionization creates a biomimetic extraction (BE) procedure
      that has the potential to simplify aquatic hazard assessments of petroleum
      substances since the total moles of all hydrocarbons sorbed to the fiber can be
      related to toxic thresholds in target lipid of aquatic organisms. The objective
      of this work is to describe the technical basis for applying BE measurements to
      predict toxicity of petroleum substances. Critical BE-based PDMS concentrations
      corresponding to adverse effects were empirically derived from toxicity tests on
      different petroleum substances with multiple test species. The resulting species
      sensitivity distribution (SSD) of PDMS effect concentrations was then compared
      and found consistent with the previously reported target lipid-based SSD.
      Further, BE data collected on samples of aqueous media dosed with a wide range of
      petroleum substances were highly correlated to predicted toxic units derived
      using the PETROTOX model. These findings provide justification for applying BE in
      environmental hazard and risk evaluations of petroleum substances and related
      mixtures.

PMID- 29455129
TI  - Comparative study of volatile organic compounds in ambient air using observed
      mixing ratios and initial mixing ratios taking chemical loss into account - A
      case study in a typical urban area in Beijing.
AB  - Volatile organic compounds (VOCs) can react with atmospheric radicals while being
      transported after being emitted, resulting in substantial losses. Using only
      observed VOC mixing ratios to assess VOC pollution, is therefore problematic. The
      observed mixing ratios and initial mixing ratios taking chemical loss into
      consideration were performed using data for 90 VOCs in the atmosphere in a
      typical urban area in Beijing in winter 2013 to gain a more accurate view of VOC
      pollution. The VOC sources, ambient VOC mixing ratios and compositions,
      variability and influencing factors, contributions to near-ground-ozone and
      health risks posed were assessed. Source apportionment should be conducted using
      initial mixing ratios, but health risks should be assessed using observed mixing
      ratios. The daytime daily mean initial mixing ratio (72.62ppbv) was 7.72ppbv
      higher than the daytime daily mean observed mixing ratio (64.90ppbv). Alkenes
      contributed >70% of the consumed VOCs. The nighttime daily mean observed mixing
      ratio was 71.66ppbv, 6.76ppbv higher than the daytime mixing ratio. The observed
      mixing ratio for 66 VOCs was 40.31% higher in Beijing than New York. The OFPs of
      Ini-D (266.54ppbv) was underestimated 23.41% compared to the OFP of Obs-D
      (204.14ppbv), improving emission control of ethylene and propene would be an
      effective way of controlling O3. Health risk assessments performed for 28
      hazardous VOCs show that benzene, chloroform, 1,2-dichloroethane, and
      acetaldehyde pose carcinogenic risk and acrolein poses non-carcinogenic risks.
      Source apportionment results indicated that vehicle exhausts, solvent usage and
      industrial processes were the main VOC source during the study.

PMID- 29455130
TI  - Structural and functional characteristics of buffer strip vegetation in an
      agricultural landscape - high potential for nutrient removal but low potential
      for plant biodiversity.
AB  - Vegetated buffer strips constitute a transition zone between terrestrial and
      aquatic ecosystems and provide several ecosystem services. Buffer strips are
      often applied as a mitigation measure against diffuse pollution in agricultural
      areas, primarily because they may retain nutrients and in this way help protect
      the aquatic environment. Additionally, they can improve biodiversity in an
      otherwise homogenous landscape and may therefore have a value in their own right.
      In the present study, we characterized the structural and functional features of
      the vegetation in Danish buffer strips using a nationwide dataset to explore: i)
      their floristic quality in terms of species diversity and conservation value and
      ii) based on their functional characteristics, their potential to retain
      nutrients. Moreover, we analyzed how the structural and functional
      characteristics varied along gradients in the environmental features of the
      catchment. We found that the floristic quality of the buffer vegetation was
      generally low, exhibiting an average of only 3.3% of the number of species of
      conservation interest. Instead, Danish buffer strips were dominated by widespread
      and productive species that are tolerant of anthropogenic impacts in the
      catchment. The abundance of highly productive plant species was positively
      related to high intensity land use, whereas the abundance of stress-tolerant
      plant species was positively related to low intensity land use. The high
      productivity of the buffer strips implies a large bio-storage potential, and
      these areas might therefore offer an opportunity to remove nutrients by
      harvesting the plant biomass. We discuss how Danish buffer strips could be
      exploited via appropriate management (e.g. harvesting) to maximize nutrient
      retention and at the same time improve floristic quality.

PMID- 29455131
TI  - Downscaling hydrodynamics features to depict causes of major productivity of
      Sicilian-Maltese area and implications for resource management.
AB  - Chlorophyll-a (CHL-a) and sea surface temperature (SST) are generally accepted as
      proxies for water quality. They can be easily retrieved in a quasi-near real time
      mode through satellite remote sensing and, as such, they provide an overview of
      the water quality on a synoptic scale in open waters. Their distributions evolve
      in space and time in response to local and remote forcing, such as winds and
      currents, which however have much finer temporal and spatial scales than those
      resolvable by satellites in spite of recent advances in satellite remote-sensing
      techniques. Satellite data are often characterized by a moderate temporal
      resolution to adequately catch the actual sub-grid physical processes.
      Conventional pointwise measurements can resolve high-frequency motions such as
      tides or high-frequency wind-driven currents, however they are inadequate to
      resolve their spatial variability over wide areas. We show in this paper that a
      combined use of near-surface currents, available through High-Frequency (HF)
      radars, and satellite data (e.g., TERRA and AQUA/MODIS), can properly resolve the
      main oceanographic features in both coastal and open-sea regions, particularly at
      the coastal boundaries where satellite imageries fail, and are complementary
      tools to interpret ocean productivity and resource management in the Sicily
      Channel.

PMID- 29455132
TI  - Rapid sewage pollution assessment by means of the coverage of epilithic taxa in a
      coastal area in the SW Atlantic.
AB  - The sewage pollution impact over coastal environment represents one of the main
      reasons explaining the deterioration of marine coastal ecosystems around the
      globe. This paper aims to detect promptly a putative sewage pollution impact in a
      Southwestern Atlantic coastal area of Argentina as well as to identify a
      straightforward way for monitoring, based on the relative abundance coverage of
      the intertidal epilithic taxa. Four sampling sites were distributed at increased
      distances from the sewage outfall where the cover of individual epilithic species
      was visually estimated. The surrounded outfall area (i.e. outfall site) resulted
      polluted with high percentages of organic matter in sediment and Enterococcus
      concentration in seawater. The structure of the community showed a remarkable
      difference between the polluted site (outfall site) and the unpolluted sites. The
      polychaete Boccardia proboscidea dominated the outfall site with variable
      abundances of the green algae Ulva sp. during the period of study, decreasing the
      diversity of the community, while the mussel Brachidontes rodriguezii and
      variable abundances of several algae species dominated the unpolluted sites. The
      monitoring of the benthic community represents an effective, non-destructive,
      relative inexpensive and rapid method to assess the health of the coastal
      environment in the study area. The large abundance of B. proboscidea along with
      the absence of B. rodriguezii individuals at <300m to the sewage outfall
      discharge allowed the success of this classical monitoring method in a temperate
      marine-coastal ecosystem with certain gradient of pollution.

PMID- 29455133
TI  - Viscous effects on the interaction of granular particles with floating oils in
      water.
AB  - Light hydrophobic liquids (LHLs) can be submerged in water with granular
      particles by forming particle encapsulated liquid sacks. Formation and
      submergence of granular encapsulated LHL sacks can be an effective method for
      capturing and controlling the fate of floating oils. However, formation
      characteristics of the LHL sacks and effect of LHL viscosity on their behavior
      are not well understood. In this study, we examined the encapsulation
      characteristics of LHL sacks depending on liquid viscosity. Silicone oils with
      viscosities ranging from 10cSt to 1000cSt were used as the LHLs. Sand with two
      different particle sizes (40-100mesh and 20-30mesh) were used as the granular
      particles. The submerged LHL sacks were stable and remained separate from each
      other without collapsing or aggregating over time. They could be moved in water
      by sliding while keeping their encapsulation.

PMID- 29455134
TI  - The increase of soil organic carbon as proposed by the "4/1000 initiative" is
      strongly limited by the status of soil development - A case study along a
      substrate age gradient in Central Europe.
AB  - During COP 21 in Paris 2015, several states and organizations agreed on the
      "4/1000" initiative for food security and climate. This initiative aims to
      increase world's soil organic carbon (SOC) stocks by 40/00 annually. The
      influence of soil development status on SOC dynamics is very important but
      usually not considered in studies. We analyse SOC accumulation under forest,
      grassland and cropping systems along a soil age gradient (10-17,000years) to show
      the influence of soil development status on SOC increase. SOC stocks (0-40cm) and
      accumulation rates along a chronosequence in alluvial soils of the Danube River
      in the Marchfeld (eastern Austria) were analysed. The analysed Fluvisols and
      Chernozems have been used as forest, grassland and cropland for decades or
      hundreds of years. The results showed that there is a fast build-up of OC stocks
      (0-40cm) in young soils with accumulation of ~1.3tha-1a-1 OC in the first
      100years and ~0.5tha-1a-1 OC between 100 and 350years almost independent of land
      use. Chernozems with a sediment deposition age older than 5.000years have an
      accumulation rate<0.01tOCha-1a-1 (0-40cm). Radiocarbon dating showed that the
      topsoil (0-10cm) consists mainly of ">modern" and "modern" carbon indicating a
      fast carbon cycling. Carbon in subsoil is less exposed to decomposition and OC
      can be stored at long-time scales in the subsoil (14C age of 3670+/-35 BP). In
      view of the '4/1000' initiative, soils with constant carbon input (forest &
      grassland) fulfil the intended 40/00 growth rate of SOC stocks only in the first
      60years of soil development. We proclaim that under the present climate in
      Central Europe, the increase of SOC stocks in soil is strongly affected by the
      state of soil development.

PMID- 29455135
TI  - Distinguishing two phenotypes of blooms using the normalised difference peak
      valley index (NDPI) and Cyano-Chlorophyta index (CCI).
AB  - Harmful algal blooms are now widely recognised as a severe threat to freshwater
      ecosystems, particularly in semi-fluvial environments created by river damming.
      Given the high spatial and temporal variability of cyanobacterial blooms, remote
      sensing is more suitable than conventional field surveys in monitoring blooms.
      However, the majority of existing algorithms cannot distinguish cyanobacterial
      blooms from eukaryotic algal blooms by extracting spectral features in the remote
      sensing reflectance (Rrs). In this study, in situ Rrs spectra of cyanobacterial
      and green algal blooms in Lakes Gaoyang, Hanfeng and Changshou of the Three
      Gorges Reservoir (TGR) in China were recorded. Characteristic spectral indices,
      namely, the normalised difference peak-valley index and Cyano-Chlorophyta index,
      were used to develop an algorithm that can effectively distinguish cyanobacterial
      and green algal blooms. The proposed algorithm was also used to investigate the
      spatio-temporal dynamics of the two phenotypes of blooms derived from Huan Jing 1
      charge-coupled device images. The resulting accuracy of 93.5% demonstrated that
      remote sensing technology, in conjunction with field observation, could
      efficiently differentiate bloom-forming species and assess the water quality in
      the TGR.

PMID- 29455136
TI  - Acclimation process of cultivating Chlorella vulgaris in toxic excess sludge
      extract and its response mechanism.
AB  - Chlorella vulgaris was cultivated in the gradually increased proportion of toxic
      sludge extracts for acclimation, which was obtained from SBR treated synthetic
      wastewater containing mixed chlorophenols (2,4,6-trichlorophenol and 4
      chlorophenol). The growth of C. vulgaris was obviously improved after acclimation
      with the cell number in the 100% sludge group was 22.75+/-0.85*106cellmL-1, which
      was relatively more than the BG11 control group's (20.80+/-0.35*106cellmL-1) and
      apparently over the 100% sludge group (10.78+/-0.45*106cellmL-1). Compared with
      the sludge control sludge group, C. vulgaris in the acclimation group gained
      24.1% and 18.2% more relative removal rate about TOC and ecotoxicity,
      respectively. Proteomics analysis showed that protein spots were more clear and
      centralized and the clarifications of the different protein spots narrowed from 8
      to 5 after acclimation. Proteins related to oxidoreducase activity and energy
      metabolism were over expressed and C. vulgaris could select the metabolic
      pathways, especially enhanced pyruvate fermentation, TCA cycle, and glycolysis
      after acclimation, by over accumulating the corresponding vital enzymes.
      Conclusively, acclimation was a good method to improve the removal ability and
      growth of C. vulgaris and algae could acclimatize itself to grow upon the toxic
      sludge extracts by metabolic selection. We suppose acclimation process was a
      potential method for algae wastewater treatment and algae cultivation without or
      reduce dilution.

PMID- 29455137
TI  - Can the watershed non-point phosphorus pollution be interpreted by critical soil
      properties? A new insight of different soil P states.
AB  - The physicochemical properties of surface soil play a key role in the fate of
      watershed non-point source pollution. Special emphasis is needed to identify soil
      properties that are sensitive to both particulate P (PP) pollution and dissolved
      P (DP) pollution, which is essential for watershed environmental management. The
      Chaohu Lake basin, a typical eutrophic lake in China, was selected as the study
      site. The spatial features of the Non-point Source (NPS) PP loads and DP loads
      were calculated simultaneously based on the integration of sediment delivery
      distributed model (SEDD) and pollution loads (PLOAD) model. Then several critical
      physicochemical soil properties, especially various soil P compositions, were
      innovatively introduced to determine the response of the critical soil properties
      to NPS P pollution. The findings can be summarized: i) the mean PP load value of
      the different sub-basins was 5.87 kg, and PP pollution is regarded to be the
      primary NPS P pollution state, while the DP loads increased rapidly under the
      rapid urbanization process. ii) iron-bound phosphorus (Fe-P) and aluminum-bound
      phosphorus (Al-P) are the main components of available P and showed the most
      sensitive responses to NPS PP pollution, and the correlation coefficients were
      approximately 0.9. Otherwise, the residual phosphorus (Res-P) was selected as a
      sensitive soil P state that was significantly negatively correlated with the DP
      loads. iii) The DP and PP concentrations were represented differently when they
      were correlated with various soil properties, and the clay proportion was
      strongly negatively related to the PP loads. Meanwhile, there is a non-linear
      relationship between the DP loads and the critical soil properties, such as Fe
      and Total Nitrogen (TN) concentrations. Specifically, a strong inhibitory effect
      of TN concentration on the DP load was apparent in the Nanfei river (NF) and
      Paihe (PH) river basins where the R2 reached 0.67, which contrasts with the
      relatively poor relationship within the other five basins. In addition, the
      degree of correlation between the Fe and DP loads severely degraded in the basins
      that were mostly covered by construction land or those that underwent a rapid
      urbanization process. The findings indicate that land use/cover change (LUCC),
      especially the distribution of agricultural land and construction land, as well
      as the soil background information (TN, Fe and Soil organic matters, etc.) can be
      considered as factors that influence NPS P pollution.

PMID- 29455138
TI  - Lichen-biocrust diversity in a fragmented dryland: Fine scale factors are better
      predictors than landscape structure.

PMID- 29455139
TI  - Implications of movement for species distribution models - Rethinking
      environmental data tools.
AB  - Movement is considered an essential process in shaping the distributions of
      species. Nevertheless, most species distribution models (SDMs) still focus solely
      on environment-species relationships to predict the occurrence of species.
      Furthermore, the currently used indirect estimates of movement allow to assess
      habitat accessibility, but do not provide an accurate description of movement.
      Better proxies of movement are needed to assess the dispersal potential of
      individual species and to gain a more practical insight in the interconnectivity
      of communities. Telemetry techniques are rapidly evolving and highly capable to
      provide explicit descriptions of movement, but their usefulness for SDMs will
      mainly depend on the ability of these models to deal with hitherto unconsidered
      ecological processes. More specifically, the integration of movement is likely to
      affect the environmental data requirements as the connection between
      environmental and biological data is crucial to provide reliable results.
      Mobility implies the occupancy of a continuum of space, hence an adequate
      representation of both geographical and environmental space is paramount to study
      mobile species distributions. In this context, environmental models, remote
      sensing techniques and animal-borne environmental sensors are discussed as
      potential techniques to obtain suitable environmental data. In order to provide
      an in-depth review of the aforementioned methods, we have chosen to use the
      modelling of fish distributions as a case study. The high mobility of fish and
      the often highly variable nature of the aquatic environment generally complicate
      model development, making it an adequate subject for research. Furthermore,
      insight into the distribution of fish is of great interest for fish stock
      assessments and water management worldwide, underlining its practical relevance.

PMID- 29455140
TI  - Comparison of soil organic carbon speciation using C NEXAFS and CPMAS 13C NMR
      spectroscopy.
AB  - We compared synchrotron-based C near-edge X-ray absorption fine structure
      (NEXAFS) and CPMAS 13C nuclear magnetic resonance (NMR) spectroscopy with respect
      to their precision and accuracy to quantify different organic carbon (OC) species
      in defined mixtures of soil organic matter source compounds. We also used both
      methods to quantify different OC species in organic surface horizons of a Histic
      Leptosol as well as in mineral topsoil and subsoil horizons of two soils with
      different parent material, stage of pedogenesis, and OC content (Cambisol: 15-30
      OC mgg-1, Podzol: 0.9-7 OC mgg-1). CPMAS 13C NMR spectroscopy was more accurate
      and precise (mean recovery of different C functional groups 96-103%) than C
      NEXAFS spectroscopy (mean recovery 92-113%). For organic surface and topsoil
      samples, NMR spectroscopy consistently yielded larger O-alkyl C percentages and
      smaller alkyl C percentages than C NEXAFS spectroscopy. For the Cambisol subsoil
      samples both methods performed well and showed similar C speciation results.
      NEXAFS spectroscopy yielded excellent spectra with a high signal-to-noise ratio
      also for OC-poor Podzol subsoil samples, whereas this was not the case for CPMAS
      13C NMR spectroscopy even after sample treatment with HF. Our results confirm the
      analytical power of CPMAS 13C NMR spectroscopy for a reliable quantitative OC
      speciation in soils with >10mgOCg-1. Moreover, they highlight the potential of
      synchrotron-based C NEXAFS spectroscopy as fast, non-invasive method to semi
      quantify different C functional groups in soils with low C content (0.9-10mgg-1).

PMID- 29455141
TI  - Comparison of scoring tools for the prediction of in-hospital mortality in status
      epilepticus.
AB  - PURPOSE: Several scoring tools have been developed for the prognostication of
      outcome after status epilepticus (SE). In this study, we compared the
      performances of STESS (Status Epilepticus Severity Score), mSTESS (modified
      STESS), EMSE-EAL (Epidemiology-based Mortality Score in Status Epilepticus-
      Etiology, Age, Level of Consciousness) and END-IT (Encephalitis-NCSE-Diazepam
      resistance-Image abnormalities-Tracheal intubation) in predicting in-hospital
      mortality after SE. METHOD: Data collected retrospectively from a cohort of 287
      patients with SE were used to calculate STESS, mSTESS, EMSE-EAL, and END-IT
      scores. The differences between the scores' performances were determined by means
      of area under the ROC curve (AUC) comparisons and McNemar testing. RESULTS: The
      in-hospital mortality rate was 11.8%. The AUC of STESS (0.628; 95% confidence
      interval (CI), 0.529-0.727) was similar to that of mSTESS (0.620; 95% CI, 0.510
      0.731), EMSE-EAL (0.556; 95% CI, 0.446-0.665), and END-IT (0.659; 95% CI, 0.550
      0.768; p > .05 for each comparison) in predicting in-hospital mortality. STESS
      with a cutoff of 3 was found to have lowest specificity and number of correctly
      classified episodes. EMSE-EAL with a cutoff at 40 had highest specificity and
      showed a trend towards more correctly classified episodes while sensitivity
      tended to be low. END-IT with a cutoff of 3 had the most balanced sensitivity
      specificity ratio. CONCLUSIONS: EMSE-EAL is as easy to calculate as STESS and
      tended towards higher diagnostic accuracy. Adding information on premorbid
      functional status to STESS did not enhance outcome prediction. END-IT was not
      superior to other scores in prediction of in-hospital mortality despite including
      information of diagnostic work-up and response to initial treatment.

PMID- 29455142
TI  - Cereal powdery mildew effectors: a complex toolbox for an obligate pathogen.
AB  - Cereal powdery mildews are major pathogens of cultivated monocot crops, and all
      are obligate biotrophic fungi that can only grow and reproduce on living hosts.
      This lifestyle is combined with extreme host specialization where every mildew
      subspecies (referred to as forma specialis) can only infect one plant species.
      Recently there has been much progress in our understanding of the possible roles
      effectors play in this complex host-pathogen interaction. Here, we review current
      knowledge on the origin, evolution, and mode of action of cereal mildew
      effectors, with a particular focus on recent advances in the identification of
      bona fide effectors and avirulence effector proteins from wheat and barley
      powdery mildews.

PMID- 29455143
TI  - The birth and death of effectors in rapidly evolving filamentous pathogen
      genomes.
AB  - Plant pathogenic fungi and oomycetes are major risks to food security due to
      their evolutionary success in overcoming plant defences. Pathogens produce
      effectors to interfere with host defences and metabolism. These effectors are
      often encoded in rapidly evolving compartments of the genome. We review how
      effector genes emerged and were lost in pathogen genomes drawing on the links
      between effector evolution and chromosomal rearrangements. Some new effectors
      entered pathogen genomes via horizontal transfer or introgression. However, new
      effector functions also arose through gene duplication or from previously non
      coding sequences. The evolutionary success of an effector is tightly linked to
      its transcriptional regulation during host colonization. Some effectors converged
      on an epigenetic control of expression imposed by genomic defences against
      transposable elements. Transposable elements were also drivers of effector
      diversification and loss that led to mosaics in effector presence-absence
      variation. Such effector mosaics within species was the foundation for rapid
      pathogen adaptation.

PMID- 29455144
TI  - Evaluation of childhood trauma with respect to criminal behavior, dissociative
      experiences, adverse family experiences and psychiatric backgrounds among prison
      inmates.
AB  - OBJECTIVE: To evaluate childhood trauma in relation to criminal behavior,
      dissociative experiences, adverse family experiences during childhood and
      psychiatric backgrounds among prison inmates. METHODS: In total, 200 prison
      inmates were included in this questionnaire-based study. Data on demographic
      characteristics, adverse family experiences during childhood and psychiatric
      backgrounds were collected via face-to-face interviews, and a psychometric
      evaluation was conducted using the Childhood Trauma Questionnaire (CTQ-28) and
      Dissociative Experiences Scale (DES). RESULTS: Several historical items were more
      common in females than in males including family history of psychiatric disease
      (23.0% vs. 13.0%, p = 0.048), a personal history of psychiatric disease (51.0%
      vs. 29.0%, p < 0.001), and previous suicide attempts (49.0% vs. 25.0%, p <
      0.001). In male inmates, in contrast, there were higher rates of substance abuse
      (48.0% vs. 29.0%, p < 0.001) and previous convictions (50.0% vs. 25.0%, p <
      0.001). Males had a younger age at first crime (24.9 +/- 8.9 years vs. 30.3 +/-
      9.2 years, p < 0.001), whereas females had higher rates of violent crimes (69.2%
      vs. 30.8% p < 0.001) and higher CTQ total scores (51.9 +/- 20.9 vs. 46.2 +/-
      18.9, p = 0.04). A significant relationship of CTQ total score was noted with age
      at first offense (beta = 0.772, p < 0.001) but not with sentence length (beta =
      0.075, p = 0.292). There were also possible mediating roles of psychiatric
      problems, adverse family experiences and DES in the relationship between CTQ and
      age at first offense. CONCLUSION: In conclusion, our findings revealed a high
      prevalence of and significant associations among childhood trauma, dissociative
      experiences, adverse family experiences and psychiatric problems in a cohort of
      incarcerated females and males. A psychiatric background, childhood trauma
      characterized by sexual abuse and violent crimes were found to be predominant in
      female prison inmates, whereas a criminal background with a younger age at first
      offense and frequent previous convictions, substance use and sexual crimes were
      more prevalent among male prison inmates. Our findings indicate a potential link
      between childhood traumatization and criminal behavior in terms of subsequent
      offending but not in terms of severity of the subsequent offense.

PMID- 29455145
TI  - Heavy metals dispersion during thermal treatment of plastic bags and its
      recovery.
AB  - One of the main worries for thermal treatment of plastic bag (PB) is the air
      pollution resulting from heavy metal (HM) evaporation and emission. The quest of
      the study was to investigate their fate during thermal treatment varying with
      temperature and atmosphere to explore the appropriate treatment technology. Four
      commonly consumed polymer bags such as PE, HDPE, LDPE and PVC were selected for
      the analysis. The elemental compositions, heating values and total metal contents
      of the samples were measured by an elemental analyzer, a sulphur/halogen
      analyzer, a bomb calorimeter and an ICP-OES, respectively. Thermal treatments of
      the samples were conducted in a tube furnace at 350, 550, 650, 750, and 850 
      degrees C with 1 L/min air or N2 gas flow, respectively. 5% HNO3/10% H2O2
      solution was used for absorbing metals from gas phase, and then HM distributions
      both in flue gas and bottom ash were determined. Results revealed that the lower
      heating values of HDPE, LDPE, PVC and PE bags were 33.32, 34.28, 24.82 and 36.7
      MJ/kg, respectively indicating energy recovery potential. Thermal treatment
      showed the maximum mass reduction (>90%) of PB at 850  degrees C. The higher
      percentage of metals was distributed in ash at initial temperature that promoted
      to gas with rise of temperature. The used absorption solution exhibited
      tremendous quantity of metals recovery. However, there was no significant
      difference between using air and N2 gas flow during treatment of PB.

PMID- 29455146
TI  - Global variations in pesticide regulations and health risk assessment of maximum
      concentration levels in drinking water.
AB  - Pesticides are used worldwide in agricultural, residential garden, and commercial
      applications. The control of pesticide exposure is a worldwide problem since
      pesticide can enter human body via ingestion, inhalation, and dermal contact. For
      drinking water, many regulatory jurisdictions respond by specifying the maximum
      concentration level (MCL) of a pesticide that may occur. At least 145 regulatory
      jurisdictions in 103 nations have specified at least 5474 pesticide MCLs in
      drinking water. Unfortunately, regulatory agencies often disagree on the
      magnitude of MCLs. For individual pesticides, MCLs often vary five, six, or even
      seven orders of magnitude. An analysis of the drinking water MCL distributions of
      the 25 most commonly regulated pesticides (N > 100 MCLs each) is presented in
      this study. Health risk uncertainty models are applied to compute uncertainty
      bounds around realistic MCL values for each pesticide and to help examine whether
      these MCLs can protect human health or not. Results indicated that at least 162
      MCLs for 23 of the 25 pesticides considered were found to exceed upper human
      health risk uncertainty bounds indicating that these MCLs may not be adequate to
      protect human health. Also, health risk characterization factors were computed
      based on the estimation of maximum legal exposures to quantify human health
      damage caused by drinking water pesticide MCLs, and results indicated that some
      pesticide MCLs could cause over 19,000 Disability-Adjusted Life Years (DALYs) per
      million population. These MCLs distributions are highly influenced by several
      value clusters dominated by U.S., World Health Organization, and European Union
      (EU) indicating that consensus MCLs may be emerging for these most commonly
      regulated pesticides.

PMID- 29455147
TI  - Investigation of amino-grafted TiO2/reduced graphene oxide hybrids as a novel
      photocatalyst used for decomposition of selected organic dyes.
AB  - A novel type of photocatalyst - hybrids of amino-grafted titania and reduced
      graphene oxide - was synthesized by a hydrothermal method. The hybrids were
      comprehensively analyzed, including determination of their morphology (TEM),
      porous structure parameters (low-temperature N2 sorption) and crystalline
      structure (XRD). Additionally, to confirm the effective bonding of the amino
      grafted titania and reduced graphene oxide, Raman and X-ray photoelectron
      spectroscopy (XPS) were used, in addition to elemental analysis. The key stage of
      the research was an evaluation of the photocatalytic activity of the synthesized
      hybrid photocatalysts with respect to the decomposition of C.I. Basic Blue 9 and
      C.I. Basic Red 1 dyes. It was found that the amino-grafted titania/reduced
      graphene oxide hybrids exhibited better photocatalytic activity in the
      degradation of C.I. Basic Blue 9 and C.I. Basic Red 1 than amino-grafted TiO2
      alone. The high efficiency of dye decomposition can be attributed to the higher
      BET surface area and good separation of photogenerated electrons and holes
      offered by graphene oxide.

PMID- 29455148
TI  - Examining the impacts of urban form on air pollutant emissions: Evidence from
      China.

PMID- 29455149
TI  - Influence of process variables in a continuous treatment of non-sterile hospital
      wastewater by Trametes versicolor and novel method for inoculum production.
AB  - Micropollutants such as pharmaceutical active compounds, present at high
      concentration in hospital wastewater (HWW), pose both environmental and human
      health challenges. Fungal reactors can effectively remove such contaminants and
      produce non-toxic effluents, but their ability to operate for a long period of
      time is yet to be demonstrated in real hospital wastewater. Several process
      variables need to be studied beforehand. Here, variables: pellet size, aeration
      and carbon-to-nitrogen ratio are studied in continuous operations with real HWW.
      Moreover, a novel strategy for inoculum production that could reduce economical
      and operational costs is proposed and tested. Optimum pellet size was found to be
      2 mm and an aeration of 0.8 L min-1 was needed to maintain fungal viability. The
      carbon-to-nitrogen ratio of 7.5 was selected and the pellet production time was
      reduced from 6 to 3 days. The novel low-cost inoculum preparation produced
      pellets with the same characteristics as the traditionally prepared ones.

PMID- 29455150
TI  - Fixed bed column study for water defluoridation using neem oil-phenolic resin
      treated plant bio-sorbent.
AB  - Fluoride has both detrimental and beneficial effects on living beings depending
      on the concentration and consumption periods. The study presented in this article
      investigated the feasibility of using neem oil phenolic resin treated
      lignocellulosic bio-sorbents for fluoride removal from water through fixed bed
      column study. Results indicated that treated bio-sorbents could remove fluoride
      both from synthetic and groundwater with variable bed depth, flow rate, fluoride
      concentration and column diameter. Data obtained from this study indicated that
      columns with the thickest bed, lowest flow rate, and fluoride concentration
      showed best column performance. Bio-sorbents used in this study are regenerable
      and reusable for more than five cycles. The initial materials cost needed to
      remove one gram of fluoride also found to be lower than the available
      alternatives. This makes the process more promising candidate to be used for
      fluoride removal. In addition, the process is also technically advantageous over
      the available alternatives.

PMID- 29455151
TI  - Nutrient management via struvite precipitation and recovery from various
      agroindustrial wastewaters: Process feasibility and struvite quality.
AB  - Improving environmental protection and finding sustainable and renewable
      resources of nutrients are core issues in circular bioeconomy. Thus, this study
      evaluated the efficiency of recovering struvite, MgNH4PO4.6H2O, from different
      agro-industrial wastewaters (four highly loaded reject waters of anaerobically co
      digested agro-industrial waste and a raw swine slurry) and assessed the quality
      of recovered struvite crystals and their reusability as fertilizer. The
      efficiency of crystallization (Ec 40-80%) and amount of struvite in the
      precipitate (Pp 55-94%) highly varied due to the characteristics of influent
      wastewaters, particularly to the content of competing elements, such as alkaline
      and heavy metals and total solids (TS). In particular, Ec (94, 75, 61%) and Pp
      (76, 66, 48%) decreased at increasing TS (0.57, 0.73, 0.99%), demonstrating the
      hindering effect of solid content on struvite recovery and quality. According to
      X-ray diffraction analysis, the structure of all isolated samples corresponded to
      crystalline, orthorhombic struvite, which exhibited high purity (32-48 g/kgd N,
      114-132 g/kgd P, and 99-116 g/kgd Mg) containing only a few foreign elements,
      whose amount depended on the characteristics of the influent wastewater. All
      struvite contained other plant macronutrients (K, Ca) and many micronutrients
      (Fe, Na, Cu, Mn, Co, Zn) that further enhance its agronomic value. Therefore,
      this study showed that struvite can be successfully recovered from a wide range
      of highly loaded agroindustrial wastewaters, and that the quality of the
      recovered struvite could be suitable for reuse in agriculture.

PMID- 29455152
TI  - Local plant responses to global problems: Dactylis glomerata responses to
      different traffic pollutants on roadsides.
AB  - The growing number of road vehicles is a major source of regional and global
      atmospheric pollution increasing concentrations of CO2 in the air, and levels of
      metals in air and soil. Nevertheless, the effects of these pollutants on plants
      growing at roadsides are poorly documented. We carried out an observational study
      of unmanipulated plants growing by the road, to identify the morpho-physiological
      responses in a perennial grass Dactylis glomerata. Firstly, we wanted to know the
      general effect of traffic intensity and ambient CO2 and its interactions on
      different plant traits. Accordingly, we analyzed the photosynthetic response by
      field A/Ci Response Curves, SLA, pigment pools, foliar nitrogen, carbohydrates
      and morphological traits in plants at three distances to the road. Secondly, we
      wanted to know if Dactylis glomerata plants can accumulate metals present on the
      roadside (Pb, Zn, Cu, and Sr) in their tissues and rhizosphere, and the effect of
      these metals on morphological traits. The MANCOVA whole model results shown: 1) a
      significant effect of road ambient CO2 concentration on morphological traits (not
      affected by traffic intensity, P interaction CO2 x traffic intensity>0.05), that
      was mainly driven by a significant negative relationship between the
      inflorescence number and ambient CO2; 2) a positive and significant relationship
      between ambient CO2 and the starch content in leaves (unaffected by traffic
      intensity); 3) a reduction in Jmax (electron transport rate) at high traffic
      intensity. These lines of evidences suggest a decreased photosynthetic capacity
      due to high traffic intensity and high levels of ambient CO2. In addition, Pb,
      Cu, Zn and Sr were detected in Dactylis glomerata tissues, and Cu accumulated in
      roots. Finally, we observed that Dactylis glomerata individuals growing at the
      roadside under high levels of CO2 and in the presence of metal pollutants,
      reduced their production of inflorescences.

PMID- 29455153
TI  - The recovery of estuarine quality and the perceived increase of cultural
      ecosystem services by beach users: A case study from northern Spain.
AB  - In Europe, the quality of coastal bathing waters improved considerably in the
      last decades, mainly due to the more demanding legislation and the adoption of
      water sanitation plans. In the Nerbioi estuary (North Spain), the Wastewater
      Treatment Plan implemented between 1990 and 2001 resulted on an abrupt decrease
      in microbial concentration; thus, complying with bathing waters legislation and
      allowing recreational activities again in the three beaches of the estuary.
      However, little is known about how improvements in bathing waters influences the
      provision of cultural ecosystem services and human well-being. A questionnaire
      was used to study beach users' behaviour and perceptions and compared with
      environmental time-series data (microbial concentration and water transparency).
      Most respondents perceived an improvement in bathing waters quality and linked it
      to the estuarine sanitation. Nerbioi beaches are important recreational areas,
      mainly for local visitors, and water quality improvement was found to be a
      critical factor for deciding to visit these beaches. Furthermore, most visitors
      answered that they would not return if water conditions deteriorate. Significant
      differences existed between beaches, with the most inner beach presenting worse
      environmental conditions than the other two beaches; and matching user's
      perceptions. Our findings highlight that water sanitation actions are important
      for the recovery of degraded coastal environments and for the maintenance of
      ecosystem services. Also, that multidisciplinary research is necessary to better
      comprehend the links between environmental recovery and the provision of
      ecosystem services.

PMID- 29455154
TI  - Transfemoral thrombectomy in the cavernous sinus and superior ophthalmic vein.
AB  - Cavernous sinus thrombosis (CST) is a rare condition that can cause death,
      neurologic disability, and visual loss. A pre-teen with septic CST leading to
      ocular hypertension and acute visual loss was treated at our institution with
      thrombectomy and thrombolysis of the cavernous sinuses and superior ophthalmic
      veins. Successful recanalization of the bilateral cavernous sinuses and superior
      ophthalmic veins was achieved in two separate procedures without complication.
      The patient showed immediate symptomatic relief. He was neurologically intact
      without visual deficits at the 2 month follow-up. This is the first report in the
      literature showing the feasibility of cavernous sinus thrombectomy using current
      devices and techniques. Early endovascular therapy may help preserve vision in
      patients with acute CST.

PMID- 29455156
TI  - Antisense oligonucleotides and other genetic therapies made simple.
AB  - Many genetic neurological diseases result from the dysfunction of single
      proteins. Genetic therapies aim to modify these disease-associated proteins by
      targeting the RNA and DNA precursors. This review provides a brief overview of
      the main types of genetic therapies, with a focus on antisense oligonucleotides
      (ASOs) and RNA interference (RNAi). We use examples of new genetic therapies for
      spinal muscular atrophy, Duchenne muscular dystrophy and familial amyloid
      polyneuropathy to highlight the different mechanisms of action of ASOs and RNAi.

PMID- 29455155
TI  - Newly designed 11-gene panel reveals first case of hereditary amyloidosis
      captured by massive parallel sequencing.
AB  - AIMS: Amyloidosis is caused by deposition of abnormal protein fibrils, leading to
      damage of organ function. Hereditary amyloidosis represents a monogenic disease
      caused by germline mutations in 11 amyloidogenic precursor protein genes. One of
      the important but non-specific symptoms of amyloidosis is hypertrophic
      cardiomyopathy. Diagnostics of hereditary amyloidosis is complicated and the real
      cause can remain overlooked. We aimed to design hereditary amyloidosis gene panel
      and to introduce new next-generation sequencing (NGS) approach to investigate
      hereditary amyloidosis in a cohort of patients with hypertrophic cardiomyopathy
      of unknown significance. METHODS: Design of target enrichment DNA library
      preparation using Haloplex Custom Kit containing 11 amyloidogenic genes was
      followed by MiSeq Illumina sequencing and bioinformatics identification of
      germline variants using tool VarScan in a cohort of 40 patients. RESULTS: We
      present design of NGS panel for 11 genes (TTR, FGA, APOA1, APOA2, LYZ, GSN, CST3,
      PRNP, APP, B2M, ITM2B) connected to various forms of amyloidosis. We detected one
      mutation, which is responsible for hereditary amyloidosis. Some other single
      nucleotide variants are so far undescribed or rare variants or represent common
      polymorphisms in European population. CONCLUSIONS: We report one positive case of
      hereditary amyloidosis in a cohort of patients with hypertrophic cardiomyopathy
      of unknown significance and set up first panel for NGS in hereditary amyloidosis.
      This work may facilitate successful implementation of the NGS method by other
      researchers or clinicians and may improve the diagnostic process after
      validation.

PMID- 29455157
TI  - Improving Outcomes After Myocardial Infarction in the US Population.

PMID- 29455158
TI  - American Heart Association's Life's Simple 7 at Middle Age and Prognosis After
      Myocardial Infarction in Later Life.
AB  - BACKGROUND: The American Heart Association recommends focusing on 7 health
      factors (Life's Simple 7) for primordial prevention of cardiovascular health.
      However, whether greater adherence to Life's Simple 7 in midlife improves
      prognosis after myocardial infarction (MI) in later life is unknown. METHODS AND
      RESULTS: In 1277 participants who developed MI during the ARIC (Atherosclerosis
      Risk in Communities) Study follow-up, a 14-point score of Life's Simple 7 was
      constructed according to the status (2 points for ideal, 1 point for
      intermediate, and 0 points for poor) of each of 7 factors (smoking, adiposity,
      physical activity, diet, total cholesterol, blood pressure, and fasting glucose)
      at baseline (1987-1989). Hazard ratios for composite and individual adverse
      outcomes of all-cause mortality, cardiovascular mortality, recurrent MI, heart
      failure, and stroke were calculated according to Life's Simple 7 score. During a
      median follow-up of 3.3 years, 918 participants (72%) had subsequent adverse
      outcomes after MI. Life's Simple 7 score at middle age was inversely associated
      with adverse outcomes after MI (adjusted hazard ratios of composite outcome, 0.57
      [95% confidence interval, 0.39-0.84] if score is >=10, 0.78 [95% confidence
      interval, 0.57-1.07] if score is 7-9, and 0.82 [95% confidence interval, 0.60
      1.11] if score is 4-6 versus <=3). The association was largely independent of
      access to care and MI severity. Individual factors related to better prognosis
      after MI were ideal nonsmoking, body mass index, blood pressure, and fasting
      glucose. CONCLUSIONS: Optimal Life's Simple 7 at middle age was associated with
      better prognosis after MI in later life. Our findings suggest a secondary
      prevention benefit of having better cardiovascular health status in midlife.

PMID- 29455159
TI  - A case of paternal uniparental isodisomy for chromosome 7 associated with
      overgrowth.
AB  - BACKGROUND: Paternal uniparental disomy for chromosome 7 (upd(7)pat) is extremely
      rare, and only four cases have been previously reported. As these cases were
      accompanied by autosomal-recessive disorders which are likely to be involved in
      growth restriction, the relevance of upd(7)pat to the overgrowth phenotype
      remains unclear. Here we describe one case of upd(7)pat with no additional
      genetic diseases, which may answer the question. METHODS: A 5-year-old Japanese
      boy presented with a tall stature of unknown causes. To detect the genetic cause
      of the tall stature, we performed Sanger sequencing, targeted resequencing,
      comparative genomic hybridisation and single-nucleotide polymorphism (SNP) array
      analyses, methylation analysis and microsatellite analysis. RESULTS: We could not
      detect pathogenic variants in causative genes for overgrowth syndrome or apparent
      copy number alterations. DNA methylation analysis revealed hypomethylation at the
      GRB10, PEG1 and PEG10 differentially methylated regions. SNP array and
      microsatellite analyses suggested paternal uniparental isodisomy for chromosome
      7. Furthermore, we could not identify homozygous mutations of known causative
      genes for inherited disorders on chromosome 7. CONCLUSION: We report the first
      case of upd(7)pat with an overgrowth phenotype.

PMID- 29455160
TI  - Children and adolescents' experiences of primary lymphoedema: semistructured
      interview study.
AB  - BACKGROUND: Congenital lymphoedema is a lifelong condition that has detrimental
      physical and psychosocial outcomes for young patients and burdensome treatment
      responsibilities that may hamper patients' motivation for self-management. There
      is limited research from the perspective of young people with primary
      lymphoedema. We aimed to describe the experiences and views of children and
      adolescents with lymphoedema to inform patient-centred practice. METHODS: Twenty
      patients (aged 8-21 years) with primary lymphoedema were purposively sampled from
      two paediatric clinics in Sydney, Australia, to participate in a semistructured
      interview. The transcripts were analysed thematically. RESULTS: We identified six
      themes: reinforcing abnormality (damaging self-esteem, self-consciousness,
      frustrating restrictions and isolation); negotiating uncertainties (fearing
      condition worsening, deprioritised and sidelined, questioning cause and
      permanence, widespread unawareness); vulnerability and caution (avoiding pain and
      discomfort, preventing severe and permanent consequences, depending on
      permission, limiting goals and aspirations); disruptive transition (resisting
      change, losing progress and support, avoiding treatment costs); developing
      resilience (focusing on the positives, embracing individuality, recalibrating
      normality, prioritising coping) and taking responsibility (individualising
      treatment, needing support, external pressure and motivation, sticking to a
      routine, seeking independence). CONCLUSION: Children and adolescents learn to
      adjust to the daily demands of lymphoedema management by individualising and
      accepting their treatment, but many continue to struggle with their self-esteem
      and lifestyle restrictions. Strategies are needed to empower young patients to
      advocate for themselves during their transition to adult care. Treatment plans
      that minimise social restrictions, address emotional consequences and incorporate
      patients' preferences could improve adherence, satisfaction and outcomes.

PMID- 29455161
TI  - Assessing factors associated with long-term work disability after cancer in
      Belgium: a population-based cohort study using competing risks analysis with a 7
      year follow-up.
AB  - OBJECTIVES: The number of workers with cancer has dramatically increasing
      worldwide. One of the main priorities is to preserve their quality of life and
      the sustainability of social security systems. We have carried out this study to
      assess factors associated with the ability to work after cancer. Such insight
      should help with the planning of rehabilitation needs and tailored programmes.
      PARTICIPANTS: We conducted this register-based cohort study using individual data
      from the Belgian Disability Insurance. Data on 15 543 socially insured Belgian
      people who entered into the long-term work disability between 2007 and 2011 due
      to cancer were used. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the
      duration of work disability using Kaplan-Meier and the cause-specific cumulative
      incidence of ability to work stratified by age, gender, occupational class and
      year of entering the work disability system for 11 cancer sites using the Fine
      and Gray model allowing for competing risks. RESULTS: The overall median time of
      work disability was 1.59 years (95% CI 1.52 to 1.66), ranging from 0.75 to 4.98
      years. By the end of follow-up, more than one-third of the disabled cancer
      survivors were able to work (35%). While a large proportion of the women were
      able to work at the end of follow-up, the men who were able to work could do so
      sooner. Being women, white collar, young and having haematological, male genital
      or breast cancers were factors with the bestlikelihood to be able to return to
      work. CONCLUSION: Good prognostic factors for the ability to work were youth,
      woman, white collar and having breast, male genital or haematological cancers.
      Reviewing our results together with the cancer incidence predictions up to 2025
      offers a high value for social security and rehabilitation planning and for
      ascertaining patients' perspectives.

PMID- 29455162
TI  - Evaluation of learning from Practical Obstetric Multi-Professional Training and
      its impact on patient outcomes in Australia using Kirkpatrick's framework: a
      mixed methods study.
AB  - OBJECTIVES: The aim of this study was to evaluate the implementation of the
      Practical Obstetric Multi-Professional Training (PROMPT) simulation using the
      Kirkpatrick's framework. We explored participants' acquisition of knowledge and
      skills, its impact on clinical outcomes and organisational change to integrate
      the PROMPT programme as a credentialing tool. We also aimed to assess
      participants' perception of usefulness of PROMPT in their clinical practice.
      STUDY DESIGN: Mixed methods approach with a pre-test/post-test design. SETTING:
      Healthcare network providing obstetric care in Victoria, Australia. PARTICIPANTS:
      Medical and midwifery staff attending PROMPT between 2013 and 2015 (n=508);
      clinical outcomes were evaluated in two cohorts: 2011-2012 (n=15 361 births) and
      2014-2015 (n=12 388 births). INTERVENTION: Attendance of the PROMPT programme, a
      simulation programme taught in multidisciplinary teams to facilitate teaching
      emergency obstetric skills. MAIN OUTCOME MEASURE: Clinical outcomes compared
      before and after embedding PROMPT in educational practice. SECONDARY OUTCOME
      MEASURE: Assessment of knowledge gained by participants through a qualitative
      analysis and description of process of embedding PROMPT in educational practice.
      RESULTS: There was a change in the management of postpartum haemorrhage by early
      recognition and intervention. The key learning themes described by participants
      were being prepared with a prior understanding of procedures and equipment,
      communication, leadership and learning in a safe, supportive environment.
      Participants reported a positive learning experience and increase in confidence
      in managing emergency obstetric situations through the PROMPT programme, which
      was perceived as a realistic demonstration of the emergencies. CONCLUSION:
      Participants reported an improvement of both clinical and non-technical skills
      highlighting principles of teamwork, communication, leadership and prioritisation
      in an emergency situation. An improvement was observed in management of
      postpartum haemorrhage, but no significant change was noted in clinical outcomes
      over a 2-year period after PROMPT. However, the skills acquired by medical and
      midwifery staff justify embedding PROMPT in educational programmes.

PMID- 29455163
TI  - Theory of change for the delivery of talking therapies by lay workers to
      survivors of humanitarian crises in low-income and middle-income countries:
      protocol of a systematic review.
AB  - INTRODUCTION: There is a severe shortage of specialist mental healthcare
      providers in low-income and middle-income countries (LMICs) affected by
      humanitarian crises. In these settings, talking therapies may be delivered by non
      specialists, including lay workers with no tertiary education or formal
      certification in mental health. This systematic review will synthesise the
      literature on the implementation and effectiveness of talking therapies delivered
      by lay workers in LMICs affected by humanitarian crises, in order to develop a
      Theory of Change (ToC). METHODS AND ANALYSIS: Qualitative, quantitative and mixed
      methods studies assessing the implementation or effectiveness of lay-delivered
      talking therapies for common mental disorders provided to adult survivors of
      humanitarian crises in LMICs will be eligible for inclusion. Studies set in high
      income countries will be excluded. No restrictions will be applied to language or
      year of publication. Unpublished studies will be excluded. Seven electronic
      databases will be searched: MEDLINE, Embase, PsycINFO, PsycEXTRA, Global Health,
      Cochrane Library and ClinicalTrials.gov. Contents pages of three peer-reviewed
      journals will be hand-searched. Sources of grey literature will include resource
      directories of two online mental health networks (MHPSS.net and MHInnovation.net)
      and expert consultation. Forward and backward citation searches of included
      studies will be performed. Two reviewers will independently screen studies for
      inclusion, extract data and assess study quality. A narrative synthesis will be
      conducted, following established guidelines. A ToC map will be amended
      iteratively to take into account the review results and guide the synthesis.
      ETHICS AND DISSEMINATION: Findings will be presented in a manuscript for
      publication in a peer-reviewed journal and disseminated through a coordinated
      communications strategy targeting knowledge generators, enablers and users.
      PROSPERO REGISTRATION NUMBER: CRD42017058287.

PMID- 29455164
TI  - Surgical efficiency in femtosecond laser cataract surgery compared with
      phacoemulsification cataract surgery: a case-control study.
AB  - OBJECTIVES: To investigate differences in surgical time, the distance the
      surgical instrument travelled and number of movements required to complete manual
      phacoemulsification cataract surgery versus femtosecond laser cataract surgery.
      DESIGN: Non-randomised comparative case series. SETTING: Single surgery site,
      Moorfields Eye Hospital, UK. PARTICIPANTS: 40 cataract surgeries of 40 patients.
      INTERVENTIONS: Laser-assisted and manual phacoemulsification cataract surgery.
      Laser-assisted surgery cases were performed using the AMO Catalys platform.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Computer vision tracking software
      PhacoTracking were applied to the recordings to establish the distance the
      instrument travelled, total number of movements (the number of times an
      instrument stops and starts moving) and time taken for surgery steps including
      phacoemulsification, irrigation-aspiration (IA) and overall surgery time. The
      time taken for laser docking and delivery was not included in the analyses.
      RESULTS: Data on 19 laser-assisted and 19 manual phacoemulsification surgeries
      were analysed (two cases were excluded due to insufficient video-recording
      quality). There were no differences in the number of instrument moves, the
      distance the instrument travelled or time taken to complete the
      phacoemulsification stage. However for IA, the number of instrument moves
      (manual: mean 20 (SD 15) vs laser: mean 38 (SD 22), P=0.008) and time taken
      (manual: mean 75 s (SD 24) vs laser: mean 108 s (SD 36), P=0.003) were
      significantly greater for laser cases. For laser versus manual cases overall,
      there was no difference in number of moves or the distance the instrument
      travelled, but laser cases took longer (mean 88 s, P=0.049). CONCLUSIONS: Laser
      cataract surgery cases took longer to complete without accounting for the time
      taken to complete the laser procedure itself. This appears to be in part due to
      IA requiring more instrument manoeuvres and taking longer to complete. Data from
      a large randomised series would better elucidate this relationship.

PMID- 29455165
TI  - Community-deliverable exercise and anxiety in adults with arthritis and other
      rheumatic diseases: a systematic review with meta-analysis of randomised
      controlled trials.
AB  - BACKGROUND/PURPOSE: Given conflicting findings, the purpose of this study was to
      use the meta-analytic approach to examine the effects of exercise (aerobic,
      strength training or both) on anxiety in adults with arthritis and other
      rheumatic diseases (AORD). METHODS: Randomised controlled exercise intervention
      trials >=4weeks in adults >=18 years of age with osteoarthritis, rheumatoid
      arthritis or fibromyalgia were included. Studies were located by searching eight
      electronic databases, cross-referencing and expert review. Dual selection and
      data abstraction of studies were performed. Hedge's standardised effect size (ES)
      was calculated for each result and pooled using the recently developed inverse
      heterogeneity model. Two-tailed z-alpha values <=0.05 and non-overlapping 95% CI
      were considered statistically significant. Heterogeneity was estimated using Q
      and I2 with alpha values <=0.10 for Q considered statistically significant. Small
      study effects were examined using funnel plots and Egger's regression test. In
      addition, the number needed to treat (NNT), percentile improvement and meta
      regression were conducted. RESULTS: Of the 639 citations screened, 14 studies
      representing 926 initially enrolled participants (539 exercise, 387 control) met
      the criteria for inclusion. Length of training (mean+/-SD) averaged 15.8+/-6.7
      weeks, frequency 3.3+/-1.3 times per week and duration 28.8+/-14.3 min per
      session. Overall, statistically significant reductions in anxiety were found
      (exercise minus control changes ES=-0.40, 95% CI -0.65 to -0.15, tau2=0.14;
      Q=40.3, P=0.0004; I2 =62.8%). The NNT was 6 with a percentile improvement of
      15.5% and an estimated 5.3 million inactive US adults with AORD improving their
      anxiety if they started exercising regularly. Statistically significant small
      study effects were observed (P<0.0001). CONCLUSIONS: Exercise is associated with
      reductions in anxiety among adults with selected types of AORD. However, a need
      exists for additional, well-designed, randomised controlled trials on this topic.
      PROSPERO REGISTRATION NUMBER: CRD42016048728.

PMID- 29455166
TI  - The development of an online intervention (Care Assist) to support male
      caregivers of women with breast cancer: a protocol for a mixed methods study.
AB  - INTRODUCTION: It is projected that 17 730 women will be diagnosed with breast
      cancer in Australia in 2017, with 3114 of these predicted to be fatal. Caregiving
      for a person with cancer can significantly impact caregivers' physical and mental
      health. Many caregivers feel ill-prepared for this role, especially when care
      involves complex medical needs accompanied by the psychological challenges
      experienced following a cancer diagnosis. METHODS AND ANALYSIS: This study
      employs a convergent, parallel, mixed methods design combining an online survey
      with an optional interview. Eligible, consenting participants will be invited to
      participate in a survey to examine (1) participants' unmet needs, (2) challenges
      experienced throughout the cancer journey, (3) perceived self-efficacy to
      determine participants' level of confidence in undertaking caregiver tasks, (4)
      views regarding suitable content to include in a caregiver training intervention,
      (5) preferred method of intervention delivery (ie, website, smartphone
      application and/or interactive video), and (6) preferences for the timing of
      delivery of the intervention content (ie, ability to choose a module, access to
      the entire content or have a set order in which they receive the information).
      Caregivers will be eligible to participate if they (1) are male, (2) have
      previously cared for or are currently caring for a woman with breast cancer, (3)
      are aged over 18 years, and (4) do not currently suffer from a cognitive
      impairment or mental health condition (ie, depression, anxiety). Data analysis
      will include examination of differences in psychological outcomes and needs based
      on demographic variables, and mediation analysis to explore whether self-efficacy
      mediates the relationship between challenges, unmet needs and distress.
      Qualitative data will be analysed using thematic analysis. ETHICS AND
      DISSEMINATION: The study was reviewed and approved by two human research ethics
      committees within Australia. We anticipate two to three publications may be
      developed from the study.

PMID- 29455167
TI  - Pulmonary metastasis in rectal cancer: a retrospective study of
      clinicopathological characteristics of 404 patients in Chinese cohort.
AB  - OBJECTIVES: This study aim to investigate the incidence, timing and risk factors
      of metachronous pulmonary recurrence after curative resection in patients with
      rectal cancer. DESIGN: A retrospective cohort study. SETTING: This study was
      conducted at a tertiary referral cancer hospital. PARTICIPANTS: A total of 404
      patients with rectal cancer who underwent curative resection from 2007 to 2012 at
      Beijing Hospital were enrolled in this study. INTERVENTIONS: The pattern of
      recurrence was observed and evaluated. PRIMARY AND SECONDARY OUTCOME MEASURES:
      The incidence and timing of recurrences by site were calculated, and the risk
      factors of pulmonary recurrence were analysed. RESULTS: The 5-year disease-free
      survival for the entire cohort was 77.0%. The most common site of recurrence was
      the lungs, with an incidence of 11.4%, followed by liver. Median interval from
      rectal surgery to diagnosis of pulmonary recurrence was much longer than that of
      hepatic recurrence (20 months vs 10 months, P=0.022). Tumour location,
      pathological tumor-node-metastasis (TNM) stage and positive circumferential
      resection margin were identified as independent risk factors for pulmonary
      recurrence. A predictive model based on the number of risk factors identified on
      multivariate analysis was developed, 5-year pulmonary recurrence-free survival
      for patients with 0, 1, 2 and 3 risk factors was 100%, 90.4%, 77.3% and 70.0%,
      respectively (P<0.001). CONCLUSIONS: This study emphasised that the lung was the
      most common site of metachronous metastasis in patients with rectal cancer who
      underwent curative surgery. For patients with unfavourable risk profiles, a more
      intensive surveillance programme that could lead to the early detection of
      recurrence is strongly needed.

PMID- 29455168
TI  - Experiences of Australian men diagnosed with advanced prostate cancer: a
      qualitative study.
AB  - OBJECTIVE: To explore men's lived experience of advanced prostate cancer (PCa)
      and preferences for support. DESIGN: Cross-sectional qualitative study applying
      open-ended surveys and interviews conducted between June and November 2016.
      Interviews audio-recorded and transcribed verbatim and analysed from an
      interpretive phenomenological perspective. SETTING: Australia, nation-wide.
      PARTICIPANTS: 39 men diagnosed with advanced PCa (metastatic or castration
      resistant biochemical regression) were surveyed with 28 men subsequently
      completing a semistructured in depth telephone interview. RESULTS: Thematic
      analysis of interviews identified two organising themes: lived experience and
      supportive care. Lived experience included six superordinate themes: regret about
      late diagnosis and treatment decisions, being discounted in the health system,
      fear/uncertainty about the future, acceptance of their situation, masculinity and
      treatment effects. Supportive care included five superordinate themes:
      communication, care coordination, accessible care, shared experience/peer support
      and involvement of their partner/family. CONCLUSIONS: Life course and the health
      and social context of PCa influence men's experiences of advanced disease.
      Multimodal interventions integrating peer support and specialist nurses are
      needed that more closely articulate with men's expressed needs.

PMID- 29455169
TI  - Positron emission tomography (PET) for prediction of glioma histology: protocol
      for an individual-level data meta-analysis of test performance.
AB  - INTRODUCTION: Gliomas, the most commonly diagnosed primary brain tumours, are
      associated with varied survivals based, in part, on their histological subtype.
      Therefore, accurate pretreatment tumour grading is essential for patient care and
      clinical trial design. METHODS AND ANALYSIS: We will perform an individual-level
      data meta-analysis of published studies to evaluate the ability of different
      types of positron emission tomography (PET) to differentiate high from low-grade
      gliomas. We will search PubMed and Scopus from inception through 30 July 2017
      with no language restriction and full-text evaluation of potentially relevant
      articles. We will choose studies that assess PET using 18-Fludeoxyglucose (18F
      FDG), l-[Methyl-()11C]Methionine (11C-MET), 18F-Fluoro-Ethyl-Tyrosine (18F-FET)
      or (18)F-Fluorothymidine (18F-FLT)for grading, verified with histological
      confirmation. We will include both prospective and retrospective studies. Bias
      will be assessed by two reviewers with the Quality Assessment of Diagnostic
      Accuracy Studies-2 tool and as per method described by Deeks et al. ETHICS AND
      DISSEMINATION: Ethics approval was not applicable, as this is a meta-analytic
      study. Results of the analysis will be submitted for publication in a peer
      reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017078649.

PMID- 29455170
TI  - Comparison and validation of screening tools for substance use in pregnancy: a
      cross-sectional study conducted in Maryland prenatal clinics.
AB  - INTRODUCTION: Prescription-drug use in the USA has increased by more than 60% in
      the last three decades. Prevalence of prescription-drug use among pregnant women
      is currently estimated around 50%. Prevalence of illicit drug use in the USA is
      14.6% among pregnant adolescents, 8.6% among pregnant young adults and 3.2% among
      pregnant adults. The first step in identifying problematic drug use during
      pregnancy is screening; however, no specific substance-use screener has been
      universally recommended for use with pregnant women to identify illicit or
      prescription-drug use. This study compares and validates three existing substance
      use screeners for pregnancy-4 P's Plus, National Institute on Drug Abuse (NIDA)
      Quick Screen/Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST)
      and the Substance Use Risk Profile-Pregnancy (SURP-P) scale. METHODS AND
      ANALYSIS: This is a cross-sectional study designed to evaluate the sensitivity,
      specificity and usability of existing substance-use screeners. Recruitment occurs
      at two obstetrics clinics in Baltimore, Maryland, USA. We are recruiting 500
      participants to complete a demographic questionnaire, NIDA Quick Screen/ASSIST, 4
      P's Plus and SURP-P (ordered randomly) during their regularly scheduled prenatal
      appointment, then again 1 week later by telephone. Participants consent to
      multidrug urine testing, hair drug testing and allowing access to prescription
      drug and birth outcome data from electronic medical records. For each screener,
      reliability and validity will be assessed. Test-retest reliability analysis will
      be conducted by examining the results of repeated screener administrations within
      1 week of original screener administrations for consistency via correlation
      analysis. Furthermore, we will assess if there are differences in the validity of
      each screener by age, race and trimester. ETHICS AND DISSEMINATION: This study is
      approved by the Institutional Review Board of the University of Maryland (HP
      00072042), Baltimore, and Battelle Memorial Institute (0619-100106433). All
      participants are required to give their informed consent prior to any study
      procedure.

PMID- 29455171
TI  - Visual-motor integration and fine motor skills at 61/2 years of age and
      associations with neonatal brain volumes in children born extremely preterm in
      Sweden: a population-based cohort study.
AB  - OBJECTIVES: This exploratory study aimed to investigate associations between
      neonatal brain volumes and visual-motor integration (VMI) and fine motor skills
      in children born extremely preterm (EPT) when they reached 61/2 years of age.
      SETTING: Prospective population-based cohort study in Stockholm, Sweden, during 3
      years. PARTICIPANTS: All children born before gestational age, 27 weeks, during
      2004-2007 in Stockholm, without major morbidities and impairments, and who
      underwent MRI at term-equivalent age. MAIN OUTCOME MEASURES: Brain volumes were
      calculated using morphometric analyses in regions known to be involved in VMI and
      fine motor functions. VMI was assessed with The Beery-Buktenica Developmental
      Test of Visual-Motor Integration-sixth edition and fine motor skills were
      assessed with the manual dexterity subtest from the Movement Assessment Battery
      for Children-second edition, at 61/2 years. Associations between the brain
      volumes and VMI and fine motor skills were evaluated using partial correlation,
      adjusted for total cerebral parenchyma and sex. RESULTS: Out of 107 children born
      at gestational age <27 weeks, 83 were assessed at 61/2 years and 66/83 were
      without major brain lesions or cerebral palsy and included in the analyses. A
      representative subsample underwent morphometric analyses: automatic segmentation
      (n=34) and atlas-based segmentation (n=26). The precentral gyrus was associated
      with both VMI (r=0.54, P=0.007) and fine motor skills (r=0.54, P=0.01).
      Associations were also seen between fine motor skills and the volume of the
      cerebellum (r=0.42, P=0.02), brainstem (r=0.47, P=0.008) and grey matter (r=
      0.38, P=0.04). CONCLUSIONS: Neonatal brain volumes in areas known to be involved
      in VMI and fine motor skills were associated with scores for these two functions
      when children born EPT without major brain lesions or cerebral palsy were
      evaluated at 61/2 years of age. Establishing clear associations between early
      brain volume alterations and later VMI and/or fine motor skills could make early
      interventions possible.

PMID- 29455174
TI  - Bladder necrosis: 'A man without a bladder'.
AB  - Since the use of antibiotics, bladder necrosis has become a rare condition. We
      report a case of bladder necrosis in a 90-year-old man following urinary
      retention. After insertion of a transurethral catheter (TUC), 2 L of urine was
      evacuated. In the following days, the TUC became intermittently blocked. Adequate
      bladder drainage could not be obtained despite intensive rinsing and placement of
      a suprapubic catheter. On surgical exploration necrosis of almost the entire
      bladder wall, except for the trigone, was encountered. Surgical debridement of
      the non-viable bladder wall without opening the abdominal cavity was conducted,
      and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since
      the patient was haemodynamically unstable, construction of a urinary diversion
      was waived and urinary drainage of the Retzius cavity by the TUC was accepted,
      resulting in adequate urinary drainage without compromising renal function.

PMID- 29455172
TI  - Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic
      elements-identification of sources by whole genome sequencing: study protocol for
      an observational study in Switzerland.
AB  - INTRODUCTION: Extended-spectrum beta-lactamases (ESBL)-producing
      Enterobacteriaceae were first described in relation with hospital-acquired
      infections. In the 2000s, the epidemiology of ESBL-producing organisms changed as
      especially ESBL-producing Escherichia coli was increasingly described as an
      important cause of community-acquired infections, supporting the hypothesis that
      in more recent years ESBL-producing Enterobacteriaceae have probably been
      imported into hospitals rather than vice versa. Transmission of ESBL-producing
      Enterobacteriaceae is complicated by ESBL genes being encoded on self
      transmissible plasmids, which can be exchanged among the same and different
      bacterial species. The aim of this research project is to quantify hospital-wide
      transmission of ESBL-producing Enterobacteriaceae on both the level of bacterial
      species and the mobile genetic elements and to determine if hospital-acquired
      infections caused by ESBL producers are related to strains and mobile genetic
      elements predominantly circulating in the community or in the healthcare setting.
      This distinction is critical in prevention since the former emphasises the urgent
      need to establish or reinforce antibiotic stewardship programmes, and the latter
      would call for more rigorous infection control. METHODS AND ANALYSIS: This
      protocol presents an observational study that will be performed at the University
      Hospital Basel and in the city of Basel, Switzerland. ESBL-producing
      Enterobacteriaceae will be collected from any specimens obtained by routine
      clinical practice or by active screening in both inpatient and outpatient
      settings, as well as from wastewater samples and foodstuffs, both collected
      monthly over a 12-month period for analyses by whole genome sequencing. Bacterial
      chromosomal, plasmid and ESBL-gene sequences will be compared within the cohort
      to determine genetic relatedness and migration between humans and their
      environment. ETHICS AND DISSEMINATION: This study has been approved by the local
      ethics committee (Ethikkommission Nordwest-und Zentralschweiz) as a quality
      control project (Project-ID 2017-00100). The results of this study will be
      published in peer-reviewed medical journals, communicated to participants, the
      general public and all relevant stakeholders.

PMID- 29455175
TI  - When a polyp is not a polyp: incidental finding of a sigmoid schwannoma at first
      colonoscopic screening.
AB  - Schwannomas, peripheral nerve sheath tumours arising from Schwann cells, are
      often associated with inherited disorders such as neurofibromatosis.
      Gastrointestinal schwannomas, while rare, have been reported in those without
      personal or family history of neurofibromatosis. Diagnoses of these lesions,
      however, typically follow evaluations prompted by symptomatic presentations
      associated with abdominal pain, rectal bleeding, change in bowel habits or
      positive results on faecal occult blood tests performed for colorectal cancer
      screening. Further, management of these predominantly benign lesions commonly
      incorporates surgical resection. We present the case of a sigmoid schwannoma
      found in an asymptomatic individual on first screening colonoscopy and treated
      with complete endoscopic polypectomy with anticipated surveillance colonoscopy.

PMID- 29455176
TI  - Late diagnosis: a case of rapidly progressive extranodal NK/T cell lymphoma,
      nasal type.
AB  - Extranodal natural killer (NK)/T cell lymphoma, nasal type is a condition that
      has poor prognosis. Accurate diagnosis of lymphoma is made by pathological
      findings. We report a case of extranodal NK/T cell lymphoma, nasal type affecting
      the lung and liver and which was difficult to diagnose because of negative biopsy
      results from multiple sites. A 39-year-old man who had dry cough and fever for 1
      month was referred to our hospital. He had pancytopenia and elevated serum levels
      of lactate dehydrogenase and soluble interleukin-2 receptor. Hepatosplenomegaly
      and multiple lung nodules were found on imaging study. Specimens of bronchoscopic
      lung, percutaneous liver, bone marrow and random skin biopsies were all negative.
      Open lung biopsy was not definitive. Unfortunately, disease progression was rapid
      and fatal before results of pleural fluid cytology and a second liver biopsy
      showed extranodal NK/T cell lymphoma, nasal type. This report focused on
      diagnostic planning for rapidly progressive extranodal NK/T-cell lymphoma, nasal
      type.

PMID- 29455177
TI  - NMDAR (N-methyl-D-aspartate receptor) encephalitis in a patient with MS (multiple
      sclerosis): a rare and challenging case.
AB  - We present a rare case of N-methyl-D-aspartate receptor (NMDAR) encephalitis in a
      41-year-old Caucasian woman, who initially presented with prominent
      neuropsychiatric symptoms on the background of pre-existing multiple sclerosis.
      Here, the authors navigate the muddy water between neurology and psychiatry,
      describing the caveats of antibody testing with a misdiagnosed case of acute and
      transient psychotic episode. NMDAR encephalitis in MS is a rare condition, which
      can be easily confused with a new onset psychotic episode. This case report can
      be helpful in recognition and diagnosis of this rare condition. Making the right
      diagnosis is important since it can prevent an unnecessary radical treatment and
      long-term neuropsychiatric complications.

PMID- 29455178
TI  - Disabling pansclerotic morphoea of childhood.
AB  - Disabling pansclerotic morphoea (DPM) of childhood is a severe and often fatal
      variant of deep morphoea. It usually starts in childhood and rarely seen in
      adults. The course of the disease is progressive with lifelong morbidity in the
      form of joint contractures and immobility. The causes of mortality include
      complications such as sepsis, gangrene and cardiopulmonary involvement. Herein,
      we discuss the case of a 15-year-old girl with limb deformity and finger
      contractures, that is, bone involvement. The diagnosis of DPM of childhood was
      fortuitously made after the correction of limb deformity, when the patient was
      seen in the dermatology department for evaluation of skin discolouration on the
      thighs.

PMID- 29455179
TI  - A quintessential syndrome with a rare marvelling aetiology: Rosai-Dorfman disease
      presenting as Conus-Cauda syndrome.
AB  - A 19-year-old woman presented with a history of severe lower backache and
      asymmetric proximal lower limb weakness during the past 3 months. In addition,
      she also suffered from lower motor neuron-type bladder and bowel symptoms. On
      examination, paraparesis was noted. Further, sensory examination suggested patchy
      asymmetric sensory loss in both lower limbs with saddle anaesthesia and
      areflexia. A clinical diagnosis of Conus-Cauda syndrome was made and contrast
      enhanced MRI of the lumbar and sacral spine was done, which confirmed the
      presence of a mass lesion within the spinal canal involving the cauda equina
      extending up to the sacral level. She underwent partial resection of the lesion
      following which the neurological deficits and lower backache resolved.
      Histopathological evaluation and immunohistochemical analyses uncovered Rosai
      Dorfman disease. There was no evidence of disease elsewhere in the body. Since
      the patient improved significantly following surgery and exhibited no further
      neurological worsening, she remains under close follow-up.

PMID- 29455180
TI  - Takotsubo syndrome in a premenopausal patient.
AB  - Takotsubo syndrome is a rare clinical condition, with a pathophysiology that is
      not fully understood. Characterised by an acute and usually reversible heart
      failure, the condition is often preceded by a stressful event. For the diagnosis
      of Takotsubo syndrome to be possible, the absence of coronary artery disease as a
      cause is required. We report a case of Takotsubo syndrome in a 47-year-old woman
      of fertile age. Electrical and echocardiographic presentations were classical in
      the patient. However, abnormally elevated cardiac biomarkers were registered. The
      patient showed signs of clinical improvement, with a follow-up angiography
      excluding coronary artery disease and therefore leading to a diagnosis of
      Takotsubo syndrome.

PMID- 29455181
TI  - A child with tubulointerstitial nephritis and uveitis (TINU) syndrome.
AB  - Tubulointerstitial nephritis and uveitis syndrome is an uncommon disease,
      probably underdiagnosed in clinical practice. Its aetiology and pathogenesis
      remain unknown. This syndrome is defined by an association of uveitis and
      tubulointerstitial nephritis, with no evidence of systemic disease or infection
      that might cause both ocular and renal inflammation. Renal and ocular
      manifestations may not occur simultaneously, making the diagnosis even more
      challenging. Treatment includes topical and oral corticosteroids. Renal
      involvement usually resolves spontaneously with full recovery of kidney function,
      however uveitis can persist or recur years after its initial presentation. We
      report a case of a 13-year-old girl with tubulointerstitial nephritis and uveitis
      syndrome.

PMID- 29455182
TI  - Pulmonary inflammatory myofibroblastic tumour misdiagnosed as a round pneumonia.

PMID- 29455183
TI  - The effect of lncRNA HOTAIR on chemoresistance of ovarian cancer through
      regulation of HOXA7.
AB  - This study aimed at investigating the biological functions of long non-coding
      RNAs (lncRNAs) hox transcript antisense intergenic RNA (HOTAIR) in resistant
      ovarian cancer cells, exploring the regulation effect of HOTAIR on HOXA7, and
      investigating their influence on the chemosensitivity of ovarian cancer cells.
      Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for the
      verification of HOTAIR expression in resistant and sensitive groups. How HOTAIR
      downregulation affected cell proliferation, migration and invasion, and apoptosis
      were determined using the MTT assay and the colony formation assay, the Transwell
      assay and flow cytometry analysis, respectively. Immunohistochemistry was used to
      inspect the protein expression of HOXA7 in resistant and sensitive ovarian cancer
      tissues. The regulation relationship between HOTAIR and HOXA7 was investigated by
      qRT-PCR and Western blot. The effect of HOTAIR and HOXA7 on tumor growth was
      confirmed by the tumor xenograft model of nude mice. By knocking down HOXA7,
      HOTAIR downregulation restrained the ovarian cancer deterioration in functional
      experiments. Silencing of HOTAIR and HOXA7 could effectively inhibit tumor growth
      and increase chemosensitivity of ovarian tumors in nude mice. Downregulation of
      HOTAIR negatively affected the survival and activity of resistant ovarian cancer
      cells, and suppressed the expression of HOXA7. Silencing of HOTAIR and HOXA7
      could increase the chemosensitivity of ovarian cancer cells, thus suppressing
      tumor development.

PMID- 29455184
TI  - CSF free light chain identification of demyelinating disease: comparison with
      oligoclonal banding and other CSF indexes.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) used in immunoglobulin gamma (IgG) index
      testing and oligoclonal bands (OCBs) are common laboratory tests used in the
      diagnosis of multiple sclerosis. The measurement of CSF free light chains (FLC)
      could pose as an alternative to the labor-intensive isoelectric-focusing (IEF)
      gels used for OCBs. METHODS: A total of 325 residual paired CSF and serum
      specimens were obtained after physician-ordered OCB IEF testing. CSF kappa
      (cKFLC) and lambda FLC (cLFLC), albumin and total IgG were measured. Calculations
      were performed based on combinations of analytes: CSF sum of kappa and lambda
      ([cKFLC+cLFLC]), kappa-index (K-index) ([cKFLC/sKFLC]/[CSF albumin/serum
      albumin]), kappa intrathecal fraction (KFLCIF) {([cKFLC/sKFLC]-[0.9358*CSF
      albumin/serum albumin]^[0.6687*sKFLC]/cKFLC)} and IgG-index ([CSF IgG/CSF
      albumin]/[serum IgG/serum albumin]). RESULTS: Patients were categorized as:
      demyelination (n=67), autoimmunity (n=53), non-inflammatory (n=50), inflammation
      (n=38), degeneration (n=28), peripheral neuropathy (n=24), infection (n=13),
      cancer (n=11), neuromyelitis optica (n=10) and others (n=31). cKFLC measurement
      used alone at a cutoff of 0.0611 mg/dL showed >90% agreement to OCBs, similar or
      better performance than all other calculations, reducing the number of analytes
      and variables. When cases of demyelinating disease were reviewed, cKFLC
      measurements showed 86% clinical sensitivity/77% specificity. CONCLUSIONS: cKFLC
      alone demonstrates comparable performance to OCBs along with increased
      sensitivity for demyelinating diseases. Replacing OCB with cKFLC would alleviate
      the need for serum and CSF IgG and albumin and calculated conversions. cKFLC can
      overcome challenges associated with performance, interpretation, and cost of
      traditional OCBs, reducing costs and maintaining sensitivity and specificity
      supporting MS diagnosis.

PMID- 29455185
TI  - Performance evaluation of cobas HBV real-time PCR assay on Roche cobas 4800
      System in comparison with COBAS AmpliPrep/COBAS TaqMan HBV Test.
AB  - BACKGROUND: Hepatitis B virus (HBV) nucleic acid amplification testing (NAAT) is
      important for the diagnosis and management of HBV infection. We evaluated the
      analytical performance of the cobas HBV NAAT (Roche Diagnostics GmbH, Mannheim,
      Germany) on the cobas 4800 System in comparison with COBAS AmpliPrep/COBAS TaqMan
      HBV Test (CAP/CTM HBV). METHODS: Precision was evaluated using three levels of
      cobas HBV/HCV/HIV-1 Control Kit, and linearity was evaluated across the
      anticipated measuring range (10.0-1.0*109 IU/mL) at seven levels using clinical
      samples. Detection capability, including limit of blank (LOB), limit of detection
      (LOD) and limit of quantitation (LOQ), was verified using the 4th WHO
      International Standard for HBV DNA for NAT (NIBSC code: 10/266). Correlation
      between the two systems was compared using 205 clinical samples (102 sera and 103
      EDTA plasma). RESULTS: Repeatability and total imprecision (coefficient of
      variation) ranged from 0.5% to 3.8% and from 0.5% to 3.5%, respectively.
      Linearity (coefficient of determination, R2) was 0.999. LOB, LOD and LOQ were all
      acceptable within the observed proportion rate (85%). Correlation was very high
      between the two systems in both serum and plasma samples (correlation coefficient
      [r]=0.995). CONCLUSIONS: The new cobas HBV real-time PCR assay on the cobas 4800
      System showed reliable analytical performances.

PMID- 29455186
TI  - Thromboelastometry reveals similar hemostatic properties of purified fibrinogen
      and a mixture of purified cryoprecipitate protein components.

PMID- 29455187
TI  - Detection of EDTA-induced pseudo-leukopenia using automated hematology analyzer
      with VCS technology.

PMID- 29455188
TI  - Laboratory hemostasis: from biology to the bench.
AB  - Physiological hemostasis is an intricate biological system, where procoagulant
      and anticoagulant forces interplay and preserves blood fluidity when blood
      vessels are intact, or trigger clot formation to prevent excessive bleeding when
      blood vessels are injured. The modern model of hemostasis is divided into two
      principal phases. The first, defined as primary hemostasis, involves the platelet
      vessel interplay, whilst the second, defined as secondary hemostasis, mainly
      involves coagulation factors, damaged cells and platelet surfaces, where the so
      called coagulation cascade rapidly develops. The activation and amplification of
      the coagulation cascade is finely modulated by the activity of several
      physiological inhibitors. Once bleeding has been efficiently stopped by blood
      clot formation, dissolution of the thrombus is essential to restore vessel
      permeability. This process, known as fibrinolysis, also develops through
      coordinate action of a vast array of proteins and enzymes. An accurate diagnosis
      of hemostasis disturbance entails a multifaceted approach, encompassing family
      and personal history of hemostatic disorders, accurate collection of clinical
      signs and symptoms, integrated with laboratory hemostasis testing. Regarding
      laboratory testing, a reasonable approach entails classifying hemostasis testing
      according to cost, complexity and available clinical information. Laboratory
      workout may hence initiate with some rapid and inexpensive "screening" tests,
      characterized by high negative predictive value, then followed by second- or
      third-line analyses, specifically aimed to clarify the nature and severity of
      bleeding or thrombotic phenotype. This article aims to provide a general overview
      of the hemostatic process, and to provide some general suggestions to optimally
      facilitate laboratory hemostasis testing.

PMID- 29455189
TI  - Is it time to abandon the Nobel Prize?

PMID- 29455190
TI  - A novel paraneoplastic syndrome with acquired lipodystrophy and chronic
      inflammatory demyelinating polyneuropathy in an adolescent male with
      craniopharyngioma.
AB  - BACKGROUND: Acquired lipodystrophy, craniopharyngioma and chronic inflammatory
      demyelinating polyneuropathy (CIDP) are individually rare disorders, and have
      never before been reported in a single patient. CASE PRESENTATION: A 15-year-7
      month old Caucasian male presented with lower extremity weakness, frequent falls
      and abnormal fat distribution occurring over the previous 1 year. He was
      diagnosed with CIDP, craniopharyngioma and acquired lipodystrophy. The patient
      underwent tumor debulking and cranial irradiation for the craniopharyngioma, and
      received monthly intravenous immunoglobulin for the CIDP. The patient initially
      had some resolution of the lipodystrophy phenotype, but subsequently the abnormal
      fat distribution recurred and the patient developed additional systemic
      abnormalities, including mild pancytopenia and hepatic fibrosis. CONCLUSIONS: Our
      patient represents a novel association of acquired lipodystrophy,
      craniopharyngioma, and CIDP, possibly due to an as yet unidentified
      paraneoplastic autoantibody.

PMID- 29455191
TI  - Smith-Lemli-Opitz syndrome: clinical and biochemical correlates.
AB  - BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder
      caused by mutations in the DHCR7 gene that result in reduced cholesterol
      biosynthesis. The aim of the study was to examine the biochemical and clinical
      features of SLOS in the context of the emerging evidence of the importance of
      cholesterol in morphogenesis and steroidogenesis. METHODS: We retrospectively
      reviewed the records of 18 patients (including four fetuses) with confirmed SLOS
      and documented their clinical and biochemical features. RESULTS: Seven patients
      had branchial arch abnormalities, including micrognathia, immune dysfunction and
      hypocalcemia. Thymic abnormalities were found in three fetuses. All four patients
      with a cholesterol level of <=0.35 mmol/L died. They all had electrolyte
      abnormalities (hyperkalemia, hyponatremia, hypocalcemia), necrotizing
      enterocolitis, sepsis-like episodes and midline defects including the branchial
      and cardiac defects. Patients with cholesterol levels >=1.7 mmol/L had milder
      features and were diagnosed at 9 months to 25 years of age. All 10 patients had
      intellectual disability. One patient was found to have a novel mutation,
      c.1220A>G (p.Asn407Ser). CONCLUSIONS: We suggest that screening for adrenal
      insufficiency and for hypoparathyroidism, hypothyroidism and immunodeficiency,
      should be done routinely in infants diagnosed early with SLOS. Early diagnosis
      and intervention to correct these biochemical consequences may decrease mortality
      and improve long-term outcome in these patients.

PMID- 29455192
TI  - Cloning and expression analysis of cDNAs encoding ADP-glucose pyrophosphorylase
      large and small subunits from hulless barley (Hordeum vulgare L. var. nudum).
AB  - As an important plateau cereal crop, hulless barley is the principal food for the
      Tibetan people in China. ADP-glucose pyrophosphorylase (AGPase) is considered as
      the key enzyme for starch biosynthesis in plants. In this study, cDNAs encoding
      the small subunit (SSU I) and large subunit (LSU I) of AGPase were isolated from
      hulless barley. The results showed that SSU I and LSU I were 1438 and 1786 bp in
      length with a complete open reading frame (ORF) of 1419 and 1572 bp. The ORF
      encoded polypeptides of 472 and 523 amino acids were having calculated molecular
      masses of 52.01 and 58.23 kDa, and the pI values were 5.59 and 6.30. In addition,
      phylogenetic analysis showed that SSU I and LSU I had the same phylogenetic
      trends with some species. Furthermore, expression levels in different growth
      periods and tissues of two hulless barley varieties were analyzed by quantitative
      reverse transcription-polymerase chain reaction. Gene expression levels of SSU I
      and LSU I were consistent with the total starch accumulation rate in endosperm.
      In conclusion, our data confirmed that SSU I and LSU I played an important role
      in hulless barley starch synthesis.

PMID- 29455193
TI  - Growth Trajectory in Children with Type 1 Diabetes Mellitus: The Impact of
      Insulin Treatment and Metabolic Control.
AB  - BACKGROUND: Linear growth was reported to be negatively affected by type 1
      diabetes mellitus (T1DM), in relation to disease duration and poor metabolic
      control. It is unclear whether a subtle growth failure still persists despite the
      optimization of therapy. Our aim was to analyse pubertal growth, adult height,
      and metabolic profile in a cohort of children with T1DM undergoing intensive
      insulin treatment by multiple daily injections or continuous subcutaneous insulin
      infusion (CSII). METHODS: One-hundred and four children (51 males) with
      prepubertal onset of T1DM were prospectively followed up to final height
      attainment. RESULTS: Age at puberty onset was 11.7 +/- 1.1 years in males and
      10.9 +/- 1.3 in females. Age at adult height attainment was 16.4 +/- 1.6 years in
      males and 14.1 +/- 1.8 years in females. Pubertal height gain was 24.4 +/- 4.9 cm
      in males and 19.0 +/- 3.8 cm in females. HbA1c, HDL cholesterol, and triglyceride
      levels increased during puberty. HDL cholesterol levels were higher in patients
      treated with CSII. Height standard deviation score (SDS) at diagnosis (0.52 +/-
      1.04) was higher than target height SDS (0.01 +/- 1.07), but declined afterwards,
      and both height SDS at puberty onset (0.22 +/- 1.1) and adult height SDS (-0.1 +/
      1.02) were not significantly different from target height SDS. BMI SDS showed a
      positive trend from diagnosis to puberty onset and stabilized later (-0.04 +/-
      1.4 at T1DM onset, 0.55 +/- 2.1 at puberty onset, and 0.53 +/- 2.1 at adult
      height attainment). CONCLUSIONS: Although subtle abnormalities of growth still
      persist, the modern advancements of insulin therapy are able to normalize puberty
      and final height of children with T1DM.

PMID- 29455194
TI  - Catheter Cuff Extrusion Following Exit-Site Infection in an Immunosuppressed
      Patient: One Case and Two Lessons.

PMID- 29455195
TI  - Sildenafil-Bosentan Drug-Drug Interaction: A Word of Caution Regarding the Most
      Common Combination Therapy in Children with Advanced Pulmonary Arterial
      Hypertension.

PMID- 29455197
TI  - Incidence and Characteristics of Adrenal Crisis in Children Younger than 7 Years
      with 21-Hydroxylase Deficiency: A Nationwide Survey in Japan.
AB  - BACKGROUND/AIMS: We aimed to evaluate the incidence and characteristics of
      adrenal crisis in Japanese children with 21-hydroxylase deficiency (21-OHD).
      METHODS: We conducted a retrospective nationwide survey for the councilors of the
      Japanese Society for Pediatric Endocrinology (JSPE) regarding adrenal crisis in
      children under 7 years with 21-OHD, admitted to hospitals from 2011 through 2016.
      We defined adrenal crisis as the acute impairment of general health due to
      glucocorticoid deficiency with at least two of symptoms, signs, or biochemical
      abnormalities. RESULTS: The councilors of the JSPE in 83 institutions responded
      to this survey (response rate, 60.1%). Data analyses of 378 patients with 1,101.4
      person-years (PYs) revealed that 67 patients (17.7%) experienced at least 1
      episode of hospital admission for adrenal crisis at the median age of 2 years.
      The incidence of adrenal crisis was calculated as 10.9 per 100 PYs (95%
      confidence interval [CI] 9.6-12.2). Infections were the most common precipitating
      factors, while no factor was observed in 12.5%. Hypoglycemia occurred
      concomitantly in 27.4%. One patient died from severe hypoglycemia, resulting in a
      mortality rate of 0.09 per 100 PYs (95% CI 0.0-0.2). CONCLUSION: Adrenal crisis
      is not rare and can be accompanied by disastrous hypoglycemia in children with 21
      OHD.

PMID- 29455196
TI  - The Relationship between Hypomagnesemia and Pulmonary Function Tests in Patients
      with Chronic Asthma.
AB  - OBJECTIVE: To investigate the relationship between serum values of magnesium and
      the parameters of the pulmonary function tests (PFT) in patients with chronic
      asthma. SUBJECTS AND METHODS: This study recruited 50 patients with chronic
      stable asthma and 40 healthy individuals as a control group. Data on age, sex,
      severity of asthma, PFT, and details of drug therapy were obtained from each
      group. Serum magnesium, potassium, phosphorus, calcium, and sodium levels were
      also measured. To evaluate differences between groups, the Student t test or Mann
      Whitney U test was performed for continuous variables, and the chi2 test for
      categorical variables. RESULTS: In the asthma group, 10% (n = 9) of the patients
      had hypomagnesemia and 5.5% (n = 5) had hypophosphatemia. Patients with asthma
      were divided into two groups: the hypomagnesemic group (n = 9) and the
      normomagnesemic group (n = 41). Forced expiratory volume in 1 s (FEV1), FEV1%,
      peak expiratory flow (PEF), and PEF% were lower in the hypomagnesemic group than
      in the normomagnesemic group (p = 0.02). Multiple logistic regression analysis
      revealed a statistically significant association between hypomagnesemia and PFT
      in the hypomagnesemic asthmatic group. The correlations of age with FEV1, FEV1%,
      PEF, and PEF% were as follows: p = 0.00, r = 0.29; p = 0.00, r = 0.43; p = 0.03,
      r = 0.22; p = 0.00, r = 0.38; and p = 0.03, r = 0.22, respectively. The
      correlation of serum magnesium levels with PFT (FEV1, FEV1%, PEF, PEF%) were as
      follows: p = 0.001, r = 0.29; p = 0.001, r = 0.43; p = 0.03, r = 0.22; and p =
      0.001, r = 0.38, respectively. The other electrolytes were within the normal
      range in both groups. CONCLUSION: In this study, hypomagnesemia and
      hypophosphatemia were found to be the most common electrolyte abnormalities in
      patients with chronic stable asthma. FEV1, FEV1%, PEF, and PEF% were
      significantly lower in asthmatic patients with hypomagnesemia compared to
      asthmatic patients with normomagnesemia.

PMID- 29455198
TI  - Incidence, Survival, and Risk Factors for Adults with Acute Myeloid Leukemia Not
      Otherwise Specified and Acute Myeloid Leukemia with Recurrent Genetic
      Abnormalities: Analysis of the Surveillance, Epidemiology, and End Results (SEER)
      Database, 2001-2013.
AB  - BACKGROUND/AIM: As the knowledgebase of acute myeloid leukemia (AML) has grown,
      classification systems have moved to incorporate these new findings. METHODS: We
      assessed 32,941 patients with AML whose records are contained in the
      Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Half of all
      patients diagnosed between 2001 and 2013 did not have a World Health Organization
      (WHO) classification. Acute promyelocytic leukemia and acute panmyelosis with
      myelofibrosis were associated with the longest leukemia-specific survival (110
      and 115 months, respectively), and AML with minimal differentiation and acute
      megakaryoblastic leukemia with the shortest (30 and 28 months, respectively). For
      patients in the WHO groups AML not otherwise specified (AML-NOS) and AML with
      recurrent genetic abnormalities (AML-RGA), the risk of death was greater for
      older patients and less for married patients. Black patients with any type of AML
      NOS also had a higher risk of death. Patients whose case of AML did not receive a
      WHO classification were older and this group had a higher risk of death when
      compared to patients with a WHO type of AML-NOS. CONCLUSION: Our findings
      highlight the divergent outcomes of patients with AML and the importance of using
      the WHO classification system and demographic factors to gauge their prognosis.

PMID- 29455199
TI  - Clinical Features and Response to Treatment of Prolactinomas in Children and
      Adolescents: A Retrospective Single-Centre Analysis and Review of the Literature.
AB  - BACKGROUND: Paediatric prolactinomas are rare. The aim of this study was to
      investigate the clinical features and outcome of paediatric patients with
      prolactinomas. METHODS: In this single-centre retrospective analysis, clinical,
      biochemical, and radiological features of all paediatric patients with pituitary
      adenomas diagnosed between 2000 and 2016 were evaluated. RESULTS: Among 21
      patients with pituitary adenomas, 12 patients with prolactinomas (median age 14.2
      years, range 11-16.6 years, 8 females, 4 males) were identified (7 macro- and 5
      microprolactinomas). The most common clinical symptoms were headaches (67%) and
      pubertal delay (67%). All patients with macroprolactinomas with prolactin
      concentrations >10,000 mU/L had at least 1 pituitary hormone deficiency.
      Cabergoline as first-line treatment (n = 11, median follow-up of 37 months, range
      12-89 months) induced normoprolactinemia (n = 8), reduced the mean tumour volume
      by 80%, and ameliorated headaches (p = 0.016) and pubertal delay (p = 0.031),
      whereas intermittent moderate side effects occurred in 55%. CONCLUSION:
      Adolescents with headaches and pubertal delay should be investigated for
      prolactinomas. Treatment with cabergoline is well tolerated and effective in
      reducing clinical symptoms and prolactin concentrations was well as inducing
      tumour shrinkage. Further clinical prospective studies are needed to standardize
      paediatric treatment modalities.

PMID- 29455200
TI  - Cardiovascular and Patient Phenotype of Extended Haemodialysis: A Critical
      Analysis of Studying a Unique Patient Population.
AB  - BACKGROUND: Extended haemodialysis (EHD) has been associated with better outcomes
      compared to conventional (CHD) regimes. The cardiovascular (CV) profile of these
      patients has not been assessed in detail. METHODS: We report baseline demographic
      and CV phenotype of 36 CHD and 36 EHD participants to a longitudinal multicentre
      study. We measured pulse wave velocity (PWV), 24-h ambulatory blood pressure,
      sublingual dark-field capillaroscopy and vascular biomarkers. RESULTS: EHD
      patients were younger (p < 0.01), with less CV comorbidity (p = 0.04) and higher
      dialysis vintage (p < 0.01). Higher PWV in CHD (p = 0.02) was not independent of
      demographic differences in the 2 groups. Biomarker profiles were similar in EHD
      and CHD but abnormal compared to healthy controls. CONCLUSION: Although CV
      profiles in these 2 cohorts were similar, EHD patients were distinct from the CHD
      population in terms of age and dialysis vintage and appear to comprise a unique
      group. Direct comparison of outcomes in these groups is challenging due to
      clinical bias.

PMID- 29455201
TI  - Deterioration of Hepatic Oxygenation Precedes an Onset of Intradialytic
      Hypotension with Little Change in Blood Volume during Hemodialysis.

PMID- 29455202
TI  - Phosphate and Calcium Control in Short Frequent Hemodialysis with the NxStage
      System One Cycler: Mass Balance Studies and Comparison with Standard Thrice
      Weekly Bicarbonate Dialysis.
AB  - BACKGROUND: Short frequent dialysis with NxStage System One cycler (NSO) has
      become increasingly popular as home hemodialysis prescription. Short dialysis
      sessions with NSO might not allow adequate phosphate (P) removal. METHODS: Single
      session and weekly balances of P and calcium (Ca) were compared in 14 patients
      treated with NSO (6 sessions/week) and in 14 patients on standard bicarbonate
      dialysis (BHD). RESULTS: NSO and BHD showed similar plasma P fall, with end
      dialysis plasma P slightly lower in BHD (2.2 +/- 0.5 vs. 2.7 +/- 0.8 mg/dL, p <
      0.02). Single-session P removal was lower in NSO, but weekly removal was higher
      (3,488 +/- 1,181 mg vs. 2,634 +/- 878, p < 0.003). Plasma Ca increase was lower
      in NSO, with similar PTH fall. Ca balance varied according to start plasma Ca,
      dialysate to blood Ca gradient and net ultrafiltration. CONCLUSIONS: short,
      frequent home hemodialysis with NSO, on a 6/week-based prescription, allows
      higher weekly P removal than BHD. With the dialysate Ca concentration in use (6
      mg/dL), total plasma Ca and iCa concentration increase is lower in NSO.

PMID- 29455203
TI  - Absence of Nicotinamide Nucleotide Transhydrogenase in C57BL/6J Mice Exacerbates
      Experimental Atherosclerosis.
AB  - BACKGROUND: Mitochondrial reactive oxygen species (ROS) contribute to
      inflammation and vascular remodeling during atherosclerotic plaque formation.
      C57BL/6N (6N) and C57BL/6J (6J) mice display distinct mitochondrial redox balance
      due to the absence of nicotinamide nucleotide transhydrogenase (NNT) in 6J mice.
      We hypothesize that differential NNT expression between these animals alters
      plaque development. METHODS: 6N and 6J mice were treated with AAV8-PCSK9 (adeno
      associated virus serotype 8/proprotein convertase subtilisin/kexin type 9) virus
      leading to hypercholesterolemia, increased low-density lipoprotein, and
      atherosclerosis in mice fed a high-fat diet (HFD). Mice were co-treated with the
      mitochondria-targeted superoxide dismutase mimetic MitoTEMPO to assess the
      contribution of mitochondrial ROS to atherosclerosis. RESULTS: Baseline and HFD
      induced vascular superoxide is increased in 6J compared to 6N mice. MitoTEMPO
      diminished superoxide in both groups demonstrating differential production of
      mitochondrial ROS among these strains. PCSK9 treatment and HFD led to similar
      increases in plasma lipids in both 6N and 6J mice. However, 6J animals displayed
      significantly higher levels of plaque formation. MitoTEMPO reduced plasma lipids
      but did not affect plaque formation in 6N mice. In contrast, MitoTEMPO
      surprisingly increased plaque formation in 6J mice. CONCLUSION: These data
      indicate that loss of NNT increases vascular ROS production and exacerbates
      atherosclerotic plaque development.

PMID- 29455204
TI  - Low Skeletal Muscle Density Is Associated with Early Death in Patients with
      Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment.
AB  - BACKGROUND: Low skeletal muscle mass is associated with increased postoperative
      morbidity and worse survival following resection for perihilar cholangiocarcinoma
      (PHC). We investigated the predictive value of skeletal muscle mass and density
      for overall survival (OS) of all patients with suspected PHC, regardless of
      treatment. METHODS: Baseline characteristics and parameters regarding disease and
      treatment were collected from all patients with PHC from 2002 to 2014. Skeletal
      muscle mass and density were measured at the level of the third lumbar vertebra
      on CT. The association between skeletal muscle mass and density with OS was
      investigated using the Kaplan-Meier method and Cox survival. RESULTS: Median OS
      in 233 included patients did not differ between those with and without low
      skeletal muscle mass (p = 0.203), whereas a significantly different median OS
      (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high
      (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal
      muscle density was independently associated with decreased OS (HR 1.78, 95% CI
      1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68,
      95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected
      peritoneal or other distant metastases on imaging. CONCLUSION: A time-dependent
      effect of skeletal muscle density on OS was found in patients with PHC,
      regardless of subsequent treatment. Low skeletal muscle density may identify
      patients at risk for early death.

PMID- 29455205
TI  - Use of Array Comparative Genomic Hybridization for the Diagnosis of DiGeorge
      Syndrome in Saudi Arabian Population.
AB  - DiGeorge syndrome (DGS) is a genetic disorder known as a clinically variable
      syndrome with over 180 associated phenotypic features. It is caused by a common
      human deletion in the 22q11.2 chromosomal region and currently is affecting
      approximately 1 in 4,000 individuals. Despite the prevalence of inherited
      diseases mainly due to consanguineous marriages, the current diagnosis of DGS in
      Saudi Arabia is mainly based on conventional high-resolution chromosome banding
      (karyotyping) and FISH techniques. However, advanced genome-wide studies for
      detecting microdeletions or duplications across the whole genome are needed. The
      aim of this study is to implement and use aCGH technology in clinical diagnosis
      of the 22q11.2 deletion in Saudi Arabian DGS patients and to confirm its
      effectiveness compared to conventional FISH and chromosome banding techniques.
      Thirty suspected DGS patients were assessed for chromosome 22q11.2 deletion using
      high-resolution G-banding, FISH, and aCGH. The aCGH results were compared with
      those obtained by the other 2 cytogenetic techniques. G-banding detected the
      22q11.2 deletion in only 1 patient in the cohort. Moreover, it detected
      additional chromosomal aberrations in 3 other patients. Using FISH, allowed for
      detection of the 22q11.2 deletion in 2 out of 30 patients. Interestingly, the use
      of aCGH technique showed deletions in the chromosome 22q11.2 region in 8
      patients, indicating a 4-fold increase in diagnostic detection capacity compared
      to FISH. Our results show the effectiveness of aCGH to overcome the limitations
      of FISH and G-banding in terms of diagnostic yield and allow whole genome
      screening and detection of a larger number of deletions and/or duplications in
      Saudi Arabian DGS patients. Except for balanced translocations and inversions,
      our data demonstrate the suitability of aCGH in the diagnostics of submicroscopic
      deletion syndromes such as DGS and most chromosomal aberrations or complex
      abnormalities scattered throughout the human genome. Our results recommend the
      implementation of aCGH in clinical genomic testing in Saudi Arabia to improve the
      diagnostic capabilities of health services while maintaining the use of
      conventional cytogenetic techniques for subsequent validation or for specific and
      known aberrations whenever required.

PMID- 29455206
TI  - A Potential Mechanism for Immune Suppression by Beta-Adrenergic Receptor
      Stimulation following Traumatic Injury.
AB  - BACKGROUND: beta-Adrenergic agents suppress inflammation and may play an
      important role in posttraumatic infections. Mechanisms may include inhibition of
      MAP kinase signaling. We sought to determine whether MKP-1 contributed to
      catecholamine suppression of innate immunity and also wanted to know whether
      early catecholamine treatment after traumatic injury increases the risk of later
      nosocomial infection. METHODS: We performed experiments using THP-1 cells and
      peripheral blood mononuclear cells from healthy individuals. We exposed cells to
      epinephrine and/or LPS and measured inflammatory gene transcription and MAP
      kinase activation. We inhibited MKP-1 activity to determine its role in
      catecholamine-induced immune suppression. Finally, we studied injured subjects to
      determine whether early catecholamine treatment was associated with nosocomial
      infection. RESULTS: Epinephrine increases MKP-1 transcripts and protein and
      decreases LPS-induced p38 and JNK phosphorylation and TNF-alpha gene
      transcription. RNAi inhibition of MKP-1 at least partially restores LPS-induced
      TNF-alpha gene expression (p = 0.024). In the clinical cohort, subjects treated
      with beta-adrenergic agents had an increased risk of ventilator-associated
      pneumonia (aOR = 1.9; 95% CI = 1.3-2.6) and bacteremia (aOR = 1.5; 95% CI = 1.1
      2.3). CONCLUSIONS: MKP-1 may have a role in catecholamine-induced suppression of
      innate immunity, and exogenous catecholamines might contribute to nosocomial
      infection risk.

PMID- 29455207
TI  - Cognitive Function Declines Significantly during Haemodialysis in a Majority of
      Patients: A Call for Further Research.
AB  - INTRODUCTION: Cognitive impairment (CI) is very common condition that occurs in
      haemodialysis patients and it is associated with reduced functional capacity and
      mortality. We assessed the change in cognitive function during haemodialysis and
      associated risk factors. METHODS: All patients >=50 years, on haemodialysis for
      >=3 months, no dementia from 2 dialysis centres were selected. Cognition was
      assessed before and after a haemodialysis session using parallel versions of the
      Montreal Cognitive Assessment (MOCA) tool. Multiple regression was used to
      examine potential confounders. RESULTS: Eight-two patients completed both tests -
      median age 73 (52-91) years, 59% male, dialysis vintage 41 (3-88) months. Sixty
      two (76%) had CI at baseline. Cognition declined over dialysis (MOCA 21 +/- 4.8
      to 19.1 +/- 4.1, p < 0.001) and domains affected were attention, language,
      abstraction and delayed recall. Age and dialysis vintage were independently
      associated with decline. CONCLUSION: Cognitive function declines over a
      haemodialysis session and this has significant clinical implications over health
      literacy, self-management and tasks like driving. More research is needed to find
      the cause for this decline in cognition.

PMID- 29455208
TI  - rhIGF-1 Treatment Increases Bone Mineral Density and Trabecular Bone Structure in
      Children with PAPP-A2 Deficiency.
AB  - AIM: Our objective was to determine changes in bone mineral density (BMD),
      trabecular bone score (TBS), and body composition after 2 years of therapy with
      recombinant human insulin-like growth factor-1 (rhIGF-1) in 2 prepubertal
      children with a complete lack of circulating PAPP-A2 due to a homozygous mutation
      in PAPP-A2 (p.D643fs25*) resulting in a premature stop codon. METHODS: Body
      composition, BMD, and bone structure were determined by dual-energy X-ray
      absorptiometry at baseline and after 1 and 2 years of rhIGF-1 treatment. RESULTS:
      Height increased from 132 to 145.5 cm (patient 1) and from 111.5 to 124.5 cm
      (patient 2). Bone mineral content increased from 933.40 to 1,057.97 and 1,152.77
      g in patient 1, and from 696.12 to 773.26 and 911.51 g in patient 2, after 1 and
      2 years, respectively. Whole-body BMD also increased after 2 years of rhIGF-1
      from baseline 0.788 to 0.869 g/cm2 in patient 1 and from 0.763 to 0.829 g/cm2 in
      patient 2. After 2 years of treatment, both children had an improvement in TBS.
      During therapy, a slight increase in body fat mass was seen, with a concomitant
      increase in lean mass. No adverse effects were reported. CONCLUSION: Two years of
      rhIGF-1 improved growth, with a tendency to improve bone mass and bone
      microstructure and to modulate body composition.

PMID- 29455209
TI  - Obstructive Sleep Apnea and Otolaryngologic Manifestations in Children with
      Pseudohypoparathyroidism.
AB  - BACKGROUND/AIMS: Pseudohypoparathyroidism (PHP) is a rare, genetic disorder.
      Patients with PHP may have increased prevalence of obstructive sleep apnea (OSA)
      but this has not been prospectively studied. METHODS: We enrolled children aged 6
      18 years with PHP and matched controls. Evaluation included physical examination,
      medical history, and polysomnography. RESULTS: Fifteen children with PHP type 1A
      (PHP1A) and 15 controls completed the study. Both groups were obese (BMI 32.2 +/-
      8.7 vs. 31.7+/- 6.5). The majority of PHP1A patients required tympanostomy tubes
      (86.7%) and adenotonsillectomy (73.3%). The primary outcome, i.e., the
      obstructive disturbance index, was significantly higher in PHP1A children versus
      controls (1.8 +/- 2.3 vs. 0.6 +/- 0.5, p = 0.045). Children with PHP1A were more
      likely to have OSA compared with controls (60.0 vs. 13.3%, p = 0.008). Three
      siblings with PHP type 1B (PHP1B) were also studied (BMI 25.9 +/- 9.0). None had
      a history of adenotonsillectomy, one had tympanostomy tubes. The obstructive
      disturbance index (2.0 +/- 2.3) was similar to that of children with PHP1A. Two
      (66.7%) PHP1B participants had OSA. CONCLUSION: Children with PHP1A are at an
      increased risk for OSA compared with similarly obese peers. They also have higher
      rates of otitis media and adenotonsillar hypertrophy. Screening for OSA should be
      considered in all patients with PHP1A and possibly PHP1B though more research is
      needed.

PMID- 29455210
TI  - What We Do and Do Not Know about Women and Kidney Diseases; Questions Unanswered
      and Answers Unquestioned: Reflection on World Kidney Day and International
      Women's Day.
AB  - Chronic kidney disease affects approximately 10% of the world's adult population:
      it is within the top 20 causes of death worldwide, and its impact on patients and
      their families can be devastating. World Kidney Day and International Women's Day
      in 2018 coincide, thus offering an opportunity to reflect on the importance of
      women's health and specifically their kidney health, on the community and the
      next generations, as well as to strive to be more curious about the unique
      aspects of kidney disease in women so that we may apply those learnings more
      broadly. Girls and women, who make up approximately 50% of the world's
      population, are important contributors to society and their families. Gender
      differences continue to exist around the world in access to education, medical
      care, and participation in clinical studies. Pregnancy is a unique state for
      women, offering an opportunity for diagnosis of kidney disease, but also a state
      where acute and chronic kidney diseases may manifest, and which may impact future
      generations with respect to kidney health. There are various autoimmune and other
      conditions that are more likely to have an impact on women, with profound
      consequences for child bearing, and on the fetus. Women have different
      complications on dialysis than men, and are more likely to be donors than
      recipients of kidney transplants. In this editorial, we focus on what we do and
      do not know about women, kidney health, and kidney disease, and what we might
      learn in the future to improve outcomes worldwide.

PMID- 29455211
TI  - Intratympanic Injections of Dexamethasone in Delayed Endolymphatic Hydrops: A
      Prospective Clinical Study.
AB  - OBJECTIVE: This study was designed to evaluate the effectiveness of intratympanic
      dexamethazone (ITD) for the treatment of ipsilateral delayed endolymphatic
      hydrops (DEH). METHODS: Forty-one patients were diagnosed with ipsilateral DEH.
      Only 37 patients completed this study. Patients were randomly divided into 2
      groups. Group A (n = 16) received oral medication, and group B (n = 21) received
      ITD once weekly for 4 consecutive weeks. RESULTS: In group A, 6 patients showed
      improvement in their vertigo. Four patients (25%) showed complete vertigo
      control, and 2 patients (12.5%) showed substantial vertigo control. In group B,
      21 patients showed improvement in their vertigo, 11 patients (52%) showed
      complete vertigo control, and 10 patients (47%) showed substantial vertigo
      control. Only 1 case did not show any improvement in their vertigo. CONCLUSION:
      ITD is proven to be a valuable and promising alternative modality for the
      management of ipsilateral DEH.

PMID- 29455212
TI  - Fetal Risks and Maternal Renal Complications in Pregnancy with Preexisting
      Chronic Glomerulonephritis.
AB  - BACKGROUND Analysis the maternal and fetal risk predictors in pregnancy in
      conjunction with chronic glomerulonephritis (CGN) patients are helpful to
      understand the influence of kidney diseases on pregnancy and the effects of
      pregnancy on kidney diseases. The aim of this study was to determine the
      predictors of adverse maternal and fetal outcomes in CGN patients. MATERIAL AND
      METHODS Maternal and fetal outcomes in 64 pregnancies of CGN patients were
      retrospectively analyzed. We randomly selected 100 low-risk-pregnancy women
      without chronic kidney disease (CKD) at the same time as the control group.
      Clinical manifestations, laboratory data, medication, and outcomes during
      pregnancies of these patients were analyzed by univariate and logistic
      regression. RESULTS CGN patients were associated with higher adverse pregnancy
      outcomes versus general pregnancies. The gestational ages are shorter, and the
      incidence of preeclampsia, gestational hypertension, and abortion were increased.
      The rates of premature delivery, low birth weights, and intrauterine growth
      restriction were higher in the CGN group. Prenatal proteinuria and blood pressure
      were significantly increased compared with pre-pregnancy stage. Proteinuria
      (0.9+/-0.6 g/d vs. 0.5+/-0.3 g/d, P=0.032) and hypertension (6.9% vs. 3.4%,
      P=0.021) at 6 months after delivery were aggravated. Prenatal proteinuria >=3.5
      g/d (OR 12.22, 95%CI 3.16~47.32, P=0.001) was the maternal risk predictor in
      pregnancy. Prenatal blood pressure >=160/110 mmHg (OR 8.97, 95%CI 1.69~47.53,
      P=0.010) and uric acid >=363 MUmol/L (OR 7.35, 95%CI 1.88~28.76, P=0.004) were
      the fetal risk predictors in pregnancy in conjunction with CGN patients.
      CONCLUSIONS Maternal-fetal risks are increased in pregnancies in conjunction with
      CGN patients. Prenatal proteinuria >=3.5 g/d, BP >=160/110 mmHg, and uric acid
      >=363 MUmol/L were the maternal and fetal risk predictors in pregnancy.

PMID- 29455214
TI  - An overview of complications affecting the Central Nervous System following
      bariatric surgery.
AB  - Bariatric surgery has been considered as an effective treatment for morbid
      obesity. Apart from procedures related complications, a broad spectrum of
      neurological disorders affecting any part of neuraxis has been reported following
      BS. Central nervous system complications, although less common than peripheral
      nervous system complications, carry significant morbidity and potential
      mortality. Encephalopathy, behavioral and psychiatric disorders, myelopathy and
      optic neuropathy are the most frequently reported CNS complications. Early
      detection and prompt management may improve or completely reverse these
      neurological complications. It is essential that the treating physicians must be
      aware of their clinical manifestations and management, so early diagnosis and
      treatment can prevent patients from suffering significant neurological deficits
      and even death. This review discusses the clinical manifestations of these
      complications in detail which will help concerned physician in earlier
      recognition and hence prevent the delay in specific treatment.

PMID- 29455213
TI  - Outcomes of Organ Transplantation from Donors with a Cancer History.
AB  - BACKGROUND The inherent challenges of selecting an acceptable donor for the
      increasing number and acuity of recipients has forced programs to take increased
      risks, including accepting donors with a cancer history (DWCH). Outcomes of organ
      transplantation using organs from DWCH must be clarified. We assessed transplant
      outcomes of recipients of organs from DWCH. MATERIAL AND METHODS Retrospective
      analysis of the Scientific Registry of Transplant Recipients data from January 1,
      2000 to December 31, 2014 identified 8385 cases of transplants from DWCH. A Cox
      proportional hazard regression model and log-rank test were used to compare
      patient survival and hazard levels of various cancer types. RESULTS DWCH was an
      independent risk factor of 5-year patient survival (HR=1.089, 95% CI: 1.009
      1.176, P=0.03) and graft survival (HR=1.129, 95% CI: 1.056-1.208, P<0.01) in
      liver and heart transplantation (patient survival: HR=1.112, 95% CI: 1.057-1.170,
      P<0.01; graft survival: HR=1.244, 95% CI: 1.052-1.472, P=0.01). There was no
      remarkable difference between the 2 groups in kidney and lung transplantation.
      Donors with genitourinary and gastrointestinal cancers were associated with
      inferior outcomes in kidney transplantation. Transplantation from donors with
      central nervous system cancer resulted in poorer survival in liver transplant
      recipients. Recipients of organs from donors with hematologic malignancy and
      otorhinolaryngologic cancer had poorer survival following heart transplantation.
      CONCLUSIONS Under the current donor selection criteria, recipients of organs from
      DWCH had inferior outcomes in liver and heart transplantation, whereas organs
      from DWCH were safely applied in kidney and lung transplantation. Specific cancer
      types should be cautiously evaluated before performing certain types of organ
      transplantation.

PMID- 29455215
TI  - Stroke and seizure continue to be the major brunt of in patient neurology care.
      An observation from teaching hospital.
AB  - OBJECTIVE: To assess the burden and describe the pattern of neurological
      disorders requiring admissions in a teaching hospital of Al Khobar. METHODS: This
      is a retrospective, cross sectional study, carried out in the Neurology
      Department of King Fahd Hospital of the University from January 2009 to December
      2016. Neurological disorders were grouped as ischemic stroke, intracerebral
      hemorrhage, transient ischemic attack, cerebral venous sinus thrombosis, seizure
      disorders, central nervous system infection, multiple sclerosis, neuropathies,
      myopathies, headache, dementia and miscellaneous group. Data was entered and
      analyzed by Statistical Package for the Social Science (SPSS) version 22.0 (IBM
      Corp., Armonk, NY, USA). RESULTS: The records of 1,317 patients admitted under
      Neurology Service were analyzed. Out of that, 740 (56.2%) were male and 577
      (43.8%) were female. Mean age was 46.9+?-24 years (mean+?-standard deviation).
      Ischemic stroke was the most common diagnosis (32%) followed by seizures (20%).
      Multiple sclerosis accounted for around 8% and central nervous system infections
      5% of neurological admission. CONCLUSION: Ischemic stroke was found to be the
      most common etiology for hospitalization in our study. The results of our study
      are similar to previous literature. An urgent need to control major risk factors
      such as diabetes and hypertension is warranted to minimize the burden of stroke.

PMID- 29455216
TI  - Demographic and histopathological patterns of neuro-epithelial brain tumors in
      Eastern Province of Saudi Arabia.
AB  - OBJECTIVE: To review the demographic and pathological pattern of neuro-epithelial
      brain tumors in a tertiary referral center in the Eastern Province of Saudi
      Arabia and to compare the results of our study with other national and
      international studies. METHODS: This is a retrospective chart-review study of all
      patients with neuro-epithelial brain tumors referred and treated in our center
      between January 2010 and January 2015. The age, gender, tumor location, and
      histopathology were recorded. RESULTS: The total number of cases was 149
      including 96 adult cases and 53 pediatric cases. 58% of cases were male, and 42%
      were female. The age group distribution showed 2 peaks; one in the first 5 years
      of life and the second was in the age range from 26-45 years old. Glioblastoma
      multiforme was the most common pathological type (32%), followed by
      medulloblastoma (13.3%). This study showed similar results to a previous study
      conducted in the Eastern Province in terms of age and gender distribution, but
      pathologically, the tumors diagnosed in our study were generally of a higher
      grading. When comparing our results to other international studies in nearby
      countries (Jordan and Egypt), we found similarities in pathological patterns and
      age distribution. However, when comparing our results to a western country (USA),
      we found considerable differences in the age group distribution. CONCLUSION:
      Neuro-epithelial brain tumors in Saudi Arabia affect younger population according
      to our study compared to Western countries. These findings are similar to other
      studies from Middle Eastern countries. In addition, our study showed a
      significant increase in high grade gliomas in the Eastern Province compared to an
      old historical study. This increase should be interpreted cautiously due to
      possible selection errors, changes in pathological grading, and expertise.

PMID- 29455217
TI  - Comparison of 2 methods of neuropathic pain assessment in carpal tunnel syndrome
      and hand functions.
AB  - OBJECTIVE: To compare the effectiveness of the Leeds Assessment of Neuropathic
      Symptoms and Signs Scale (LANSS) to the painDETECT questionnaire (PD-Q) in Carpal
      Tunnel Syndrome (CTS), and determine if there are any differences between hand
      related functions in the 2 questionnaires. METHODS: This prospective clinical
      trial was conducted from April to July 2014. Ninety patients with a positive
      Tinel or Phalen sign were recruited. Hands were evaluated by electromyography and
      grouped according to mild, moderate or severe involvement. Neuropathic pain was
      analysed by the LANSS and the PD-Q; hand functions were evaluated by the Duruoz
      Hand Index (DHI), Semmes Weinstein monofilaments and grip strength. RESULTS:
      Electromyographic findings revealed 32.9% of hands had mild, 61.8% had moderate
      and 5.3% had severe CTS. There was a correlation between the LANSS scores and the
      Visual Analogue Scale (VAS) pain, while the PD-Q scores were correlated with the
      VAS pain, DHI and Semmes Weinstein Monofilaments (SWM). Comparison of the hand
      related parameters of the questionnaires showed there was a statistically
      significant difference between the 2 groups with respect to the DHI and SWM tests
      in the PD-Q. However, there was no difference in the LANSS. CONCLUSION: Although
      there was a significant correlation between the LANSS and PD-Q scores, the PD-Q
      scores revealed better correlation coefficients in VAS pain, DHI scores and SWM
      tests. In conclusion, the PD-Q seems to be better than the LANSS both in
      neuropathic pain and in detecting functions related to hand abilities.

PMID- 29455218
TI  - APOE Gene polymorphism among Jordanian Alzheimer's patients with relation to
      lipid profile.
AB  - OBJECTIVE: To investigate the frequencies of the apolipoprotein E (APOE) alleles
      and genotypes and study their relationship with the lipid profile in Jordanian
      patients with late-onset Alzheimer's disease (AD). METHODS: This case-control
      study was carried out on 71 Jordanian individuals: 38 patients with late-onset AD
      (age >/=65 years) and 33 age-matched healthy controls. All participants were
      recruited from senior homes and Jordan University Hospital, Amman, Jordan between
      January 2010 and December 2013. Each sample was examined for APOE's 3 major
      isoforms (e2, e3, e4) using the polymerase chain reaction technique (PCR)
      followed by the sequencing technique. In addition, samples were screened for
      lipid profiles (total cholesterol (TC), high-density lipoprotein (HDL), lower
      density lipoprotein (LDL), and triglyceride (TG) levels. RESULTS: The e3/e4
      genotype and e4 allele prevalence were higher in AD patients compared to healthy
      controls (26.3% vs. 3.0%, p=0.03 and 15.8% vs. 4.5%, p=0.03; respectively). In
      the AD group, the e2 carriers showed the lowest levels of total and LDL
      cholesterol, and the e4 carriers showed the highest levels of total and LDL
      cholesterol, although the difference was not statistically significant (p>0.05).
      CONCLUSION: APOE-e4 frequency was almost 4 times higher in the AD group compared
      to the control group, and this difference was statistically significant. A trend
      that was observed in the AD group regarding the lipid profile and e2 and e4
      carriers requires further investigation using a larger sample size.

PMID- 29455219
TI  - Endoscopic transsphenoidal approach to skull base lesions. A clinical prospective
      study.
AB  - OBJECTIVE: To review the patients operated by endoscopic transphenoidal approach
      for skull base lesions. All the clinical data including age, gender, type of
      pathology, surgical outcome and surgical complications were studied. METHODS: A
      clinical prospective study was conducted on 94 cases with skull base lesion that
      were treated in Neuroscience Hospital in Baghdad, Iraq between October 2011 and
      December 2016. We followed each patient for an average of 2 years after surgery
      to determine most common lesion involving the skull base, age and gender
      distribution, surgical outcome, complications and hospital accommodation. Freeze
      system of Storz all the cases in the study. RESULTS: The majority of our patients
      were between the ages of 20-29 years. Among the 94 patients, 67% had macro
      adenomas, followed by craniopharyngioma 11%. The mortality rate was 2.1%, Gross
      total removal was 57.4%. All patients show improvement of the headache after
      surgery, visual improvement was noticed in 73.4% and hospital accommodation was 2
      5 days. Three patients developed cerebrospinal fluid leak, Infection meningitis
      developed in 3 patients 3.1%, and 2 patients (2.1%) suffered from hormonal
      disorders and were referred to endocrinologist for therapy. Diabetes insipidus
      developed as a temporary complication in 4 cases (4.2%). CONCLUSION:
      Trassphenoidal surgery is relatively safe surgery for properly selected patients.

PMID- 29455220
TI  - How do physical capacity, fatigue and performance differ in children with
      duchenne muscular dystrophy compared with their healthy peers?
AB  - OBJECTIVE: To compare the fatigue levels and energy expenditure of children with
      Duchenne Muscular Dystrophy (DMD) at different functional levels with healthy
      children. METHODS: The cross-sectional study was carried out in the Unit of
      Pediatric Neuromuscular Diseases in the Department of Physiotherapy and
      Rehabilitation, Faculty of Health Science, Hacettepe University between March
      2015 and January 2016. Fifty two children diagnosed with DMD in Level I-III
      according to the Brooke Functional Classification Scale and 17 healthy children
      were included in the study. The Six Minute Walk Test (6MWT), Northstar Ambulatory
      Assessment Scale (NSAA), Physiological Cost Index (PCI), and Timed performance
      tests were used to assess the children. RESULTS: Comparison in terms of PCI
      indicated a difference between Levels 2 and 3, and Levels 1 and 3 (p<0.0083). A
      difference was found in ascending and descending 4 stairs after 6MWT when fatigue
      after activity was evaluated. CONCLUSION: The walking distances, fatigue levels
      and energy expenditure of DMD patients were higher than the healthy peers. This
      difference was more prominent with decreasing functional level.

PMID- 29455221
TI  - Perioperative lumbar drain utilization in transsphenoidal pituitary resection.
AB  - OBJECTIVE: To evaluate lumbar drain (LD) efficacy in transnasal resection of
      pituitary macroadenomas in preventing postoperative cerebrospinal fluid (CSF)
      leak, technique safety, and effect on length of hospital stay. METHODS: We
      conducted a retrospective data review of pituitary tumor patients in our
      institution who underwent surgery between December 2006 and January 2013. All
      patients were operated on for complete surgical resection of pituitary
      macroadenoma tumors. Patients were divided into 2 groups: group 1 received a
      preoperative drain, while LD was not preoperatively inserted in group 2. In cases
      of tumors with suprasellar extension with anticipation of high-flow leak, LD was
      inserted after the patient was intubated and in a lateral position. Lumbar drain
      was used for 48 hours, and the drain was removed if no leak was observed
      postoperatively. In documented postoperative CSF leak patients with no
      preoperative drain, the leak was treated by LD trial prior to surgical
      reconstruction. Cases in which leak occurred 6 months postoperatively were
      excluded. RESULTS: Our study population consisted of 186 patients, 99 women (53%)
      and 87 men (47%), with a mean age of 50.3+/-16.1 years. Complications occurred in
      7 patients (13.7%) in group 1 versus 21 (15.5%) in group 2 (p=0.72).
      Postoperative CSF leak was observed in 1 patient (1.9%) in group 1 and 7 (5%) in
      group 2 (Fisher exact test=0.3). Length of hospital stay was a mean of 4.7+/-1.9
      days in group 1 and a mean of 2.7+/-2.4 days in group 2 (p<001). The most common
      reason to extend hospital stay was management of diabetes insipidus. CONCLUSION:
      Although LD insertion is generally considered safe with a low risk of
      complications, it increases the length of hospitalization. Minor complications
      include headaches and patient discomfort.

PMID- 29455222
TI  - Encephalopathy mimicking non-convulsive status Epilepticus.
AB  - Primary hyperammonemic encephalopathy due to urea cycle disorders (UCD) typically
      manifests with episodic unresponsiveness and this clinical entity is not often
      included in the differential diagnosis of presumed non-convulsive status
      epilepticus (NCSE). However, this diagnostic consideration has therapeutic
      implications. In this report, we document the therapeutic importance of
      elucidating the specific cause of hyperammonemic encephalopathy that closely
      mimicked NCSE through 2 unique illustrative cases.

PMID- 29455223
TI  - Sialidosis type I presenting with a novel mutation and advanced neuroimaging
      features.
AB  - Sialidosis is a rare lysosomal storage disease caused by neuraminidase gene
      (NEU1) mutation and a deficiency of the enzyme neuraminidase. The aim of this
      study was to examine the sialidosis type 1 brain using volumetric magnetic
      resonance imaging (MRI), diffusion tensor imaging and functional MRI in
      comparison to 3 controls. The patients gene analysis identified compound
      heterozygous mutation in the NEU1 that is shown to be associated with the
      sialidosis type 1. In this very rarely seen case, we found volume changes in
      different brain structures. We found that subthalamic nucleus volumes were found
      to be smaller in the patient compared to the controls. Also, sialidosis type 1
      had significantly smaller cerebellar volume compared with the control group. The
      case had higher mean diffusivity and lower fractional anisotropy values in the
      cerebellum and displayed abnormal functional connectivity.

PMID- 29455225
TI  - Editorial Message.

PMID- 29455224
TI  - Type and etiology of pediatric epilepsy in Jordan. A multi-center study.

PMID- 29455226
TI  - Respiratory support attitudes among pediatric intensive care staff for spinal
      muscular atrophy patients in Saudi Arabia.
AB  - OBJECTIVE: To explore therapeutic attitude of healthcare providers practicing in
      pediatric critical care in Saudi Arabia toward patients with Spinal Muscular
      Atroph (SMA) Type I, and to explore their awareness about the International
      Consensus statement for SMA care. METHODS: A cross-sectional survey was conducted
      in April 2015 during 6th Saudi Critical Care Conference, targeting physicians and
      respiratory therapists practicing in Pediatric Critical Care. RESULTS: Sixty
      participants accepted to participate in this survey. Out of those who answered
      the questionnaire, 44 were included in the analysis. Majority (66%) of
      participants were unaware of the International Consensus guidelines for SMA.
      Endotracheal intubation was reported as an acceptable intervention in SMA
      patients with acute respiratory failure by 43% of participants. Similarly,
      chronic home ventilation was agreed by 41% of participants. CONCLUSION: A
      nationwide adaptation of the International SMA Consensus guidelines for children
      with SMA I is recommended, aiming to decrease variability and standardize their
      management across various healthcare facilities in Saudi Arabia.

PMID- 29455227
TI  - The clinical features of patients concurrent with Guillain-Barre syndrome and
      myasthenia gravis.
AB  - OBJECTIVE: To evaluate all the coincidence cases of Guillain-Barre syndrome (GBS)
      and myasthenia gravis (MG). METHODS: We performed web-based research of the
      overlapping incidence of GBS and MG in studies occurring from 1982 to 2016 and
      restricted to the English language. RESULTS: Among 15 cases, an elevated CSF
      protein level without pleocytosis was found in 10 cases (66.7%); reduced nerve
      conduction was found in 13 cases (86.6%); a positive repetitive nerve stimulation
      test occurred in 11 cases (73.3%); anti-AChR antibodies were found in 13 cases
      (86.6%); anti-GQ1b antibodies were found in 6 cases (40%); a positive edrophonium
      chloride test was present in 10 cases (66.7%); and a co-occurring thymoma or
      thymectomy occurred in 4 cases (26.6%). The MG co-occurred with acute
      inflammatory demyelinating polyneuropathy (AIDP) in 8 cases and with Miller
      Fisher Syndrome in 5 cases. Treatment in the assessed cases included
      pyridostigmine (10 cases), prednisolone (7 cases), intravenous immunoglobulin (9
      cases), plasmapheresis (3 cases), combined intravenous immunoglobulin and
      plasmapheresis in one case, and immunosuppressive drugs in 2 cases
      (azathioprine). Functional outcome was mentioned in 13 patients. The prognosis
      was favorable in 8 of the 15 recorded patients (Hughes 0-1), and 2 cases resulted
      in death. CONCLUSION: Although comorbidity of GBS and MG is extremely rare, early
      recognition of this combination of inflammation of peripheral nerves and the
      neuromuscular junction is of great importance for both initial treatment and a
      better prognosis.

PMID- 29455230
TI  - Things We Do for No Reason: Hospitalization for the Evaluation of Patients with
      Low-Risk Chest Pain.

PMID- 29455229
TI  - Effect of Hospital Readmission Reduction on Patients at Low, Medium, and High
      Risk of Readmission in the Medicare Population.
AB  - BACKGROUND: Hospitalization and readmission rates have decreased in recent years,
      with the possible consequence that hospitals are increasingly filled with high
      risk patients. OBJECTIVE: We studied whether readmission reduction has affected
      the risk profile of hospitalized patients and whether readmission reduction was
      similarly realized among hospitalizations with low, medium, and high risk of
      readmissions. DESIGN: Retrospective study of hospitalizations between January
      2009 and June 2015. PATIENTS: Hospitalized fee-for-service Medicare
      beneficiaries, categorized into 1 of 5 specialty cohorts used for the publicly
      reported hospital-wide readmission measure. MEASUREMENTS: Each hospitalization
      was assigned a predicted risk of 30-day, unplanned readmission using a risk
      adjusted model similar to publicly reported measures. Trends in monthly mean
      predicted risk for each cohort and trends in monthly observed to expected
      readmission for hospitalizations in the lowest 20%, middle 60%, and highest 20%
      of risk of readmission were assessed using time series models. RESULTS: Of
      47,288,961 hospitalizations, 16.2% (n = 7,642,161) were followed by an unplanned
      readmission within 30 days. We found that predicted risk of readmission increased
      by 0.24% (P = .03) and 0.13% (P = .004) per year for hospitalizations in the
      surgery/ gynecology and neurology cohorts, respectively. We found no significant
      increase in predicted risk for hospitalizations in the medicine (0.12%, P = .12),
      cardiovascular (0.32%, P = .07), or cardiorespiratory (0.03%, P = .55) cohorts.
      In each cohort, observed to expected readmission rates steadily declined, and at
      similar rates for patients at low, medium, and high risk of readmission.
      CONCLUSIONS: Hospitals have been effective at reducing readmissions across a
      range of patient risk strata and clinical conditions. The risk of readmission for
      hospitalized patients has increased for 2 of 5 clinical cohorts.

PMID- 29455231
TI  - Impact of a Multicenter, Mentored Quality Collaborative on Hospital-Associated
      Venous Thromboembolism.
AB  - BACKGROUND: Reliable prophylaxis of hospitalassociated venous thromboembolism (HA
      VTE) is not achieved in many hospitals. Efforts to improve prophylaxis have had
      uneven results. OBJECTIVE: To reduce HA-VTE with a scalable quality improvement
      collaborative. DESIGN: A prospective, unblinded, open-intervention study with
      historical controls. PARTICIPANTS AND SETTING: All adult inpatients at 35
      community hospitals in California, Arizona, and Nevada. INTERVENTIONS: A
      centrally supported collaborative implementing standardized VTE risk assessment
      and prophylaxis. Protocols were developed with 9 "pilot" sites, which received
      individualized mentoring. Finished protocols were disseminated to 26 "spread"
      sites, which received improvement webinars without mentoring. Active surveillance
      for real-time correction of suboptimal prophylaxis was funded in pilot sites and
      encouraged in spread sites. Planning and minimal improvement work began in 2011;
      most implementation occurred in 2012 and 2013. MEASUREMENTS: Rates of per
      protocol prophylaxis (at pilot sites), and compliance with The Joint Commission
      VTE measures (all sites), were monitored starting in January 2012. The
      International Classification of Diseases, 9th Edition-Clinical Modification codes
      were used to determine the rates of HA-VTE within 30 days of discharge,
      heparininduced thrombocytopenia, and anticoagulation adverse events;
      preimplementation (2011) rates were compared with postimplementation (2014)
      rates. RESULTS: Protocol-appropriate prophylaxis rates and The Joint Commission
      measure compliance both reached 97% in 2014, up from 70% to 89% in 2012 and 2013.
      Five thousand three hundred and seventy HA-VTEs occurred during 1.16 million
      admissions. Four hundred twenty-eight fewer HA-VTEs occurred in 2014 than in 2011
      (relative risk 0.78; 95% confidence interval, 0.73-0.85). HA-VTEs fell more in
      pilot sites than spread sites (26% vs 20%). The rates of adverse events were
      reduced or unchanged. CONCLUSIONS: Collaborative efforts were associated with
      improved prophylaxis rates and fewer HA-VTEs.

PMID- 29455228
TI  - Numeracy, Health Literacy, Cognition, and 30-Day Readmissions among Patients with
      Heart Failure.
AB  - BACKGROUND: Numeracy, health literacy, and cognition are important for chronic
      disease management. Prior studies have found them to be associated with poorer
      selfcare and worse clinical outcomes, but limited data exists in the context of
      heart failure (HF), a condition that requires patients to monitor their weight,
      fluid intake, and dietary salt, especially in the posthospitalization period.
      OBJECTIVE: To examine the relationship between numeracy, health literacy, and
      cognition with 30-day readmissions among patients hospitalized for acute
      decompensated HF (ADHF). DESIGN, SETTING, PATIENTS: The Vanderbilt Inpatient
      Cohort Study is a prospective longitudinal study of adults hospitalized with
      acute coronary syndromes and/or ADHF. We studied 883 adults hospitalized with
      ADHF. MEASUREMENTS: During their hospitalization, a baseline interview was
      performed in which demographic characteristics, numeracy, health literacy, and
      cognition were assessed. Through chart review, clinical characteristics were
      determined. The outcome of interest was 30-day readmission to any acute care
      hospital. To examine the association between numeracy, health literacy,
      cognition, and 30-day readmissions, multivariable Poisson (log-linear) regression
      was used. RESULTS: Of the 883 patients admitted for ADHF, 23.8% (n = 210) were
      readmitted within 30 days; 33.9% of the study population had inadequate numeracy
      skills, 24.6% had inadequate/marginal literacy skills, and 53% had any cognitive
      impairment. Numeracy and cognition were not associated with 30-day readmissions.
      Though (objective) health literacy was associated with 30-day readmissions in
      unadjusted analyses, it was not in adjusted analyses. CONCLUSIONS: Numeracy,
      health literacy, and cognition were not associated with 30-day readmission among
      this sample of patients hospitalized with ADHF.

PMID- 29455232
TI  - Startle reflex modulation by affective face "Emoji" pictographs.
AB  - The current research was designed to assess possible differences in the emotional
      content of pleasant and unpleasant face emoji using acoustically evoked eyeblink
      startle reflex response. Stimuli were selected from Emojipedia Webpage. First, we
      assessed these stimuli with a previous independent sample of 190 undergraduate
      students (46 males and 144 females) mean age of 21.43 years (SD 3.89). A
      principal axis method was performed using the 30 selected emoji faces, extracting
      two factors (15 pleasant and 15 unpleasant emoji). Second, we measured the
      acoustic startle reflex modulation in 53 young adult women [mean age 22.13 years
      (SD 4.3)] during the viewing of each of the 30 emoji emotional faces in the
      context of the theory of motivation and emotion proposed by Lang (1995), but
      considering only the valence dimension. We expected to find higher acoustically
      evoked startle responses when viewing unpleasant emoji and lower responses for
      pleasant ones, similarly to the results obtained in the studies using human faces
      as emotional stimulus. An ANOVA was conducted to compare acoustic startle
      responses associated with pleasant and unpleasant emoji. Results yielded main
      effects for picture valence (lambda = 0.80, F(1, 50) = 12.80, p = .001, eta2 =
      0.20). Post-hoc t test analysis indicated significant differences in the startle
      response between unpleasant (50.95 +/- 1.75) and pleasant (49.14 +/- 2.49) emoji
      (t (52) = 3.59, p = .001), with a Cohen's d = 0.495. Viewing affective facial
      emoji expressions modulates the acoustic startle reflex response according to
      their emotional content.

PMID- 29455233
TI  - Mutational analysis aids the diagnosis of primary myelofibrosis with atypical
      morphology.

PMID- 29455234
TI  - Blastic plasmacytoid dendritic cell neoplasm: update on therapy especially novel
      agents.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive
      hematopoietic malignancy mainly affecting elderly patients. Most patients present
      with asymptomatic skin lesions as the first symptom and has a high frequency of
      bone marrow involvement. BPDCN is typically characterized by CD4+ and CD 56+ co
      expression without common lymphoid or myeloid lineage markers. There is no
      consensus on the optimal therapeutic strategy for BPDCN. It is highly responsive
      to chemotherapy but the median event-free survival is very short. Allogeneic stem
      cell transplantation may improve the prognosis of BPDCN but the rate of relapse
      is still high. There are no specific targeted agents approved for patients with
      BPDCN, but advances in the understanding of the pathobiology of BPDCN and the
      results of early clinical studies have revealed novel targets and potentially
      effective agents. Novel targeted therapies may improve outcomes for patients with
      BPDCN in the future.

PMID- 29455235
TI  - Enlarged spleen is associated with low neutrophil and platelet engraftment rates
      and poor survival after allogeneic stem cell transplantation in patients with
      acute myeloid leukemia and myelodysplastic syndrome.
AB  - Primary graft failure can be a cause of early morbidity and mortality after
      allogeneic hematopoietic stem cell transplantation (HSCT), as it leads to a high
      risk of severe infections and bleeding. Splenomegaly is associated with primary
      graft failure in patients of myelofibrosis, but the association between
      splenomegaly and outcomes after HSCT in patients with myeloid malignancies has
      not been previously evaluated. The aim of this study was to investigate the
      effect of spleen volume on engraftment kinetics in patients with acute myeloid
      leukemia (AML) and myelodysplastic syndrome (MDS). We enrolled 85 patients. The
      median spleen volume was 146 cm3 (quartile 88-201 cm3). The adjusted hazard
      ratios for neutrophil and platelet engraftments were 0.17 (0.07-0.40, p < 0.001)
      and 0.19 (0.05-0.69, p = 0.011), respectively, for the high-risk group, at a
      cutoff splenic volume of 320 cm3. Overall survival at 3 years after HSCT was
      significantly poor in the high-risk group with an adjusted hazard ratio of 13.8
      (2.61-72.4, p = 0.002). Enlarged spleen was associated with low neutrophil and
      platelet engraftment rates and poor survival after allogeneic HSCT in patients of
      AML and MDS.

PMID- 29455236
TI  - Brentuximab vedotin is effective for rheumatoid arthritis in a patient with
      relapsed methotrexate-associated Hodgkin lymphoma.

PMID- 29455237
TI  - Randomized controlled trial of 2% lidocaine gel versus water-based lubricant for
      multi-channel urodynamics.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of the study was to determine if there
      is a difference in pain during and after multichannel urodynamic testing in women
      when using 2% lidocaine gel versus water-based lubricant. METHODS: This was a
      randomized, controlled, double-blinded study. Women scheduled to undergo
      urodynamic testing were invited to participate. Participants were randomized to
      lidocaine 2% gel or water-based lubricant for use during testing. Both
      participant and examiner were blinded to the type of gel. Pain was assessed by
      the Wong-Baker pain scale from 0 to 10 at four points during the examination.
      After testing, participants completed a questionnaire to assess their
      expectations of pain and embarrassment with urodynamic testing. The examiner also
      completed a questionnaire to assess his/her impression of the participant's pain
      during the procedure. RESULTS: The women in the lidocaine group had lower pain
      scores after the cotton tipped swab test (1.3 vs 3.6, lidocaine vs lubricant
      respectively, p < 0.001) and after placement of urodynamic catheters (1.4 vs 3.9,
      lidocaine vs lubricant, respectively, p < 0.001). Mean pain scores 30 min post
      completion of the study were similar between groups (0.7 vs 1.2, 1.4 vs 3.9,
      lidocaine vs lubricant respectively, p = 0.19). Participants reported that pain
      during the study was better than expected in both groups. Physician perception of
      the participant's pain during testing was lower in the lidocaine group (2 vs 3,
      lidocaine vs lubricant respectively p = 0.008). CONCLUSION: Use of 2% lidocaine
      gel during in and out catheterization, cotton-tipped swab test, and urodynamic
      testing decreases pain during these procedures.

PMID- 29455238
TI  - A blinded observational cohort study of the microbiological ecology associated
      with pyuria and overactive bladder symptoms.
AB  - INTRODUCTION AND HYPOTHESIS: This study sought to characterise the microbial
      ecology of the lower urinary tract in patients with symptoms of overactive
      bladder (OAB) using culture of the urinary urothelial cell sediment. The
      pathological significance of the microbiome was assessed through its relationship
      with known urothelial inflammatory markers and patient reported symptoms.
      METHODS: Adult female patients with OAB symptoms and asymptomatic controls were
      assessed at 12 study visits scheduled every 4 weeks. At each visit, all
      participants provided a clean-catch midstream urine (MSU) that was analysed to
      count white and uroepithelial cells, submitted to standard culture and spun
      urothelial-cell-sediment culture. Symptoms were assessed using validated
      questionnaires. RESULTS: This analysis shows that OAB patients differ
      consistently from controls, demonstrating differences in bacterial ecology (t 
      4.57, p 0.0001), in the microscopic pyuria count (t -6.37, p 0.0001) and presence
      of infected urothelial cells (t -4.21, p 0.0001). The primary outcome measure of
      bacterial growth [colony-forming units (CFU) ml-1] was higher in OAB patients
      than in controls throughout the 12 months. Data showed a correlation between
      symptoms and pyuria, with notable urgency correlating with pyuria and epithelial
      cell shedding. The routine urine cultures (with a threshold of reporting a
      positive result as 105 CFU/ml) were unable to distinguish OAB patients from
      controls. However, sediment cultures differed significantly, and there was a
      correlated increased immune response amongst OAB patients. CONCLUSIONS: This
      study supports the need to re-examine the OAB phenotype given this association
      with microbial colonisation.

PMID- 29455239
TI  - Genotyping of Candidatus Syngnamydia salmonis (chlamydiales; Simkaniaceae) co
      cultured in Paramoeba perurans (amoebozoa; Paramoebidae).
AB  - Candidatus Syngnamydia salmonis (Chlamydiales, Simkaniaceae) was described as an
      epitheliocystis-causing bacterium from the gills of Atlantic salmon (Salmo salar)
      in Norway. A bacterium showing 99.2% 16S rRNA identity to Cand. S. salmonis is
      able to multiply in Paramoeba perurans and based on the classification criteria
      this bacterium could represent the same species as Cand. S. salmonis. Sequencing
      the genome of the cultured bacterium has made it possible to fulfill the minimal
      standards for genetic characterization of species within the order Chlamydiales.
      The complete rRNA genes, the amino acid sequences of SucA, PepF, Adk, HemL, DnaA,
      FtsK and FabI, are presented in addition to the morphology of the Chlamydia-like
      morphs in the cytoplasm of P. perurans.

PMID- 29455240
TI  - Taxonomic structure and function of seed-inhabiting bacterial microbiota from
      common reed (Phragmites australis) and narrowleaf cattail (Typha angustifolia
      L.).
AB  - The present study investigated the endophytic bacterial communities in the seeds
      of mature, natural common reed (Phragmites australis) and narrowleaf cattail
      (Typha angustifolia L.). Additionally, seed endophytic bacterial communities were
      compared with rhizospheric and root endophytic bacterial communities using
      Illumina-based sequencing. Seed endophytic bacterial communities were dominated
      by Proteobacteria (reed, 41.24%; cattail, 45.51%), followed by Bacteroidetes
      (reed, 12.01%; cattail, 10.41%), Planctomycetes (reed, 10.36%; cattail, 9.09%),
      Chloroflexi (reed, 8.72%; cattail, 6.45%), Thermotogae (reed, 5.43%; cattail,
      6.11%), Tenericutes (reed, 3.63%; cattail, 3.97%) and Spirochaetes (reed, 3.32%;
      cattail, 3.90%). The dominant genera were Desulfobacter (reed, 8.02%; cattail,
      8.96%), Geobacter (reed, 2.74%; cattail, 2.81%), Thiobacillus (reed, 2.71%;
      cattail, 2.41%), Sulfurimonas (reed, 2.47%; cattail, 2.31%), Methyloversatilis
      (reed, 2.29%; cattail, 2.05%) and Dechloromonas (reed, 1.13%; cattail, 1.48%).
      Obvious distinctions were observed among the respective rhizospheric, root
      endophytic and seed endophytic bacterial communities. Principal coordinate
      analysis with weighted UniFrac distance and the heat map analysis demonstrated
      that the seed endophytic bacterial communities were distinct assemblages rather
      than a subgroup of rhizobacterial communities or root endophytic bacterial
      communities. These results provide new information regarding endophytic bacteria
      associated with seeds of wetland plants and demonstrate a variety of genera that
      have a strong potential to enhance phytoremediation in the wetland ecosystem.

PMID- 29455241
TI  - COX-2-derived PGE2 triggers hyperplastic renin expression and hyperreninemia in
      aldosterone synthase-deficient mice.
AB  - Pharmacological inhibition or genetic loss of function defects of the renin
      angiotensin aldosterone system (RAAS) causes compensatory renin cell hyperplasia
      and hyperreninemia. The triggers for the compensatory stimulation of renin
      synthesis and secretion in this situation may be multimodal. Since cyclooxygenase
      2 (COX-2) expression in the macula densa is frequently increased in states of a
      defective RAAS, we have investigated a potential role of COX-2 and its derived
      prostaglandins for renin expression and secretion in aldosterone synthase
      deficient mice (AS-/-) as a model for a genetic defect of the RAAS. In comparison
      with wild-type mice (WT), AS-/- mice had 9-fold and 30-fold increases of renin
      mRNA and of plasma renin concentrations (PRC), respectively. Renin
      immunoreactivity in the kidney cortex of AS-/- mice was 10-fold higher than in
      WT. Macula densa COX-2 expression was 5-fold increased in AS-/- kidneys relative
      to WT kidneys. Treatment of AS-/- mice with the COX-2 inhibitor SC-236 for 1 week
      lowered both renal renin mRNA and PRC by 70%. Hyperplastic renin cells in AS-/-
      kidneys were found to express the prostaglandin E2 receptors EP2 and EP4. Global
      deletion of EP2 receptors did not alter renin mRNA nor PRC values in AS-/- mice.
      Renin cell-specific inducible deletion of the EP4 receptor lowered renin mRNA and
      PRC by 25% in AS-/- mice. Renin cell-specific inducible deletion of the EP4
      receptor in combination with global deletion of the EP2 receptor lowered renin
      mRNA and PRC by 70-75% in AS-/- mice. Lineage tracing of renin-expressing cells
      revealed that deletion of EP2 and EP4 leads to a preferential downregulation of
      perivascular renin expression. Our findings suggest that increased macula densa
      COX-2 activity in AS-/- mice triggers perivascular renin expression and secretion
      via prostaglandin E2.

PMID- 29455242
TI  - Heightened CXCR4 and CXCL12 expression in NF1-associated neurofibromas.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is a common autosomal dominantly
      inherited disorder that affects both the skin and the nervous system. NF1 occurs
      due to the mutations in the NF1 gene. Neurofibromas are the most common Schwann
      cell-based tumors in NF1 patients, which are mainly categorized into dermal and
      plexiform neurofibromas. Studies on different tumor types demonstrate that CXCR4
      expression increases in tumor tissues and is linked to metastasis and cancer
      progression. PURPOSE: In the present study, we aimed to analyze the gene
      expression of CXCR4, and its ligand CXCL12, in human neurofibromas. METHODS:
      Eight NF1 patients aged between 5 and 37 (2 males, 6 females) were selected. The
      patient group comprised 1 plexiform neurofibroma, 1 pheochromocytoma, and 6
      dermal neurofibromas. Following pathological examination and diagnosis, tumors
      were co-stained with antibodies against Schwann cell marker S100 and target
      molecule CXCR4. CXCR4 expression in Schwann cell-based tumors was detected at the
      protein level. RNA isolated from the same tumors was used for RT-PCR-based
      studies to measure the quantitative expression of CXCR4 and CXCL12. RESULTS:
      CXCR4 gene expression increased 3- to 120-fold and CXCL12 gene expression
      increased 33- to 512-fold in all human Schwann cell-based tumors. CONCLUSION: In
      order to validate the role of CXCR4 and its relationship with CXCL12 in NF1,
      future studies should be performed with additional tumors and different tumor
      types.

PMID- 29455244
TI  - Rotation of intramedullary alignment rods affects distal femoral cutting plane in
      total knee arthroplasty.
AB  - PURPOSE: Intramedullary rods are widely used to align the distal femoral cut in
      total knee arthroplasty. We hypothesised that both coronal (varus/valgus) and
      sagittal (extension/flexion) cutting plane are affected by rotational changes of
      intramedullary femoral alignment guides. METHODS: Distal femoral cuts using
      intramedullary alignment rods were simulated by means of a computer-aided
      engineering software in 4 degrees , 6 degrees , 8 degrees , 10 degrees , and 12
      degrees  of valgus in relation to the femoral anatomical axis and 4 degrees 
      extension, neutral, as well as 4 degrees , 8 degrees , and 12 degrees  of flexion
      in relation to the femoral mechanical axis. This reflects the different angles
      between anatomical and mechanical axis in coronal and sagittal planes. To assess
      the influence of rotation of the alignment guide on the effective distal femoral
      cutting plane, all combinations were simulated with the rod gradually aligned
      from 40 degrees  of external to 40 degrees  of internal rotation. RESULTS:
      Rotational changes of the distal femoral alignment guides affect both the coronal
      and sagittal cutting planes. When alignment rods are intruded neutrally with
      regards to sagittal alignment, external rotation causes flexion, while internal
      rotation causes extension of the sagittal cutting plane. Simultaneously the
      coronal effect (valgus) decreases resulting in an increased varus of the cutting
      plane. However, when alignment rods are intruded in extension or flexion partly
      contradictory effects are observed. Generally the effect increases with the
      degree of valgus preset, rotation and flexion. CONCLUSION: As incorrect rotation
      of intramedullary alignment guides for distal femoral cuts causes significant
      cutting errors, exact rotational alignment is crucial. Coronal cutting errors in
      the distal femoral plane might result in overall leg malalignment, asymmetric
      extension gaps and subsequent sagittal cutting errors.

PMID- 29455245
TI  - Chronic hyperinsulinemia induced miR-27b is linked to adipocyte insulin
      resistance by targeting insulin receptor.
AB  - Defect in insulin signaling leads to the development of insulin resistance
      followed by type 2 diabetes. Exploiting our previously developed physiological
      chronic hyperinsulinemia (CI)-mediated insulin resistance (IR) model, we wanted
      to understand how miRNAs contribute to the development of IR. Amongst the
      identified and validate miRNAs, the expression of miR-27b was found to be highly
      upregulated during CI-induced IR in 3T3-L1 adipocytes. We also validated the
      expression of miR-27b in CI-induced IR in human mesenchymal stem cell (hMSC)
      derived adipocytes and in vivo high fat diet (HFD)-induced IR mice model.
      Bioinformatics target prediction softwares and luciferase reporter assay
      identified insulin receptor (INSR) as one of a prime target of miR-27b.
      Lentiviral mediated overexpression of miR-27b impairs insulin signaling by
      modulating INSR expression that in turn led to decreased glucose uptake in both
      3T3-L1 and hMSC-derived adipocytes. Conversely, inhibition of miR-27b reversed CI
      mediated suppression of target protein INSR and improved phosphorylation of Akt,
      a nodal protein of insulin signaling that is impaired by CI treatment. Lentiviral
      mediated overexpression of miR-27b in in vivo C57BL/6 mice impaired whole body
      glucose tolerance and adipose tissue insulin sensitivity. Furthermore, inhibition
      of miR-27b in HFD-induced insulin resistance mice model improved glucose
      tolerance and adipose tissue insulin sensitivity by increasing the expression of
      its target gene INSR in eWAT. Thus, our results indicate that miR-27b functions
      as a prime modulator of CI-induced IR via regulating the expression of INSR. KEY
      MESSAGES: miR-27b is upregulated in different in vitro and in vivo models of
      insulin resistance. miR-27b directly suppresses the expression of INSR by
      targeting 3'UTR of INSR. Modulation of miR-27b expression regulates insulin
      sensitivity by targeting INSR.

PMID- 29455243
TI  - 2018 International Olympic Committee consensus statement on prevention, diagnosis
      and management of paediatric anterior cruciate ligament (ACL) injuries.
AB  - In October 2017, the International Olympic Committee hosted an international
      expert group of physiotherapists and orthopaedic surgeons who specialise in
      treating and researching paediatric anterior cruciate ligament (ACL) injuries.
      Representatives from the American Orthopaedic Society for Sports Medicine,
      European Paediatric Orthopaedic Society, European Society for Sports
      Traumatology, Knee Surgery and Arthroscopy, International Society of Arthroscopy
      Knee Surgery and Orthopaedic Sports Medicine, Pediatric Orthopaedic Society of
      North America, and Sociedad Latinoamericana de Artroscopia, Rodilla y Deporte
      attended. Physiotherapists and orthopaedic surgeons with clinical and research
      experience in the field, and an ethics expert with substantial experience in the
      area of sports injuries also participated. Injury management is challenging in
      the current landscape of clinical uncertainty and limited scientific knowledge.
      Injury management decisions also occur against the backdrop of the complexity of
      shared decision-making with children and the potential long-term ramifications of
      the injury. This consensus statement addresses six fundamental clinical questions
      regarding the prevention, diagnosis, and management of paediatric ACL injuries.
      The aim of this consensus statement is to provide a comprehensive, evidence
      informed summary to support the clinician, and help children with ACL injury and
      their parents/guardians make the best possible decisions.

PMID- 29455246
TI  - Notch expressed by osteocytes plays a critical role in mineralisation.
AB  - : Notch is actively involved in various life processes including osteogenesis;
      however, the role of Notch signalling in the terminal mineralisation of bone is
      largely unknown. In this study, it was noted that Hey1, a downstream target of
      Notch signalling was highly expressed in mature osteocytes compared to
      osteoblasts, indicating a potential role of Notch in osteocytes. Using a recently
      developed thermosensitive cell line (IDG-SW3), we demonstrated that dentin matrix
      acidic phosphoprotein 1 (DMP1) expression was inhibited and mineralisation
      process was significantly altered when Notch pathway was inactivated via
      administration of N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl
      ester (DAPT), an inhibitor of Notch. Dysregulation of Notch in osteocyte
      differentiation can result in spontaneous deposition of calcium phosphate on
      collagen fibrils, disturbed transportation of intracellular mineral vesicles,
      alteration of mineral crystal structure, decreased bonding force between minerals
      and organic matrix, and suppression of dendrite development coupled with
      decreased expression of E11. In conclusion, the evidence presented here suggests
      that Notch plays a critical role in osteocyte differentiation and
      biomineralisation process. KEY MESSAGES: Notch plays a regulatory role in
      osteocyte phenotype. Notch modulates the mineralisation mediated by osteocytes.
      Notch activity influences the ultrastructural properties of bone mineralisation.

PMID- 29455247
TI  - Long-term experiences of pain after a fragility fracture.
AB  - : Little is known about long-term pain after a fragility fracture. In this
      secondary analysis, we determined that pain continues to influence many patients'
      lives more than 1 year after a fracture and that health care providers do not
      seem to adequately recognize or manage these long-term consequences.
      INTRODUCTION: We characterized perspectives on long-term pain among men and women
      who had sustained a fragility fracture. METHODS: We conducted a secondary
      analysis of qualitative data from 67 individuals recruited in three primary
      studies (47-89 years old; 55 women, 12 men). Eligible individuals from the
      primary studies were those who had reported pain related to their fracture beyond
      6 months. Data about reported pain were re-analyzed using qualitative description
      as articulated by Sandelowski. RESULTS: Thirty-four individuals (47-89 years old;
      4 men; 8 had sustained a vertebral fracture) reported pain related to their
      fracture in the primary studies. Thirty-one (91%) participants had sustained a
      fragility fracture at least 1 year previously (range 1-13 years). Patients
      described long-term pain beyond typical fracture healing times, generally
      unrelieved by analgesics, which affected their mobility, functional activity,
      independence, sleep, and energy. Health care providers were perceived to under
      estimate timelines regarding the decrease of post-fracture pain and to not manage
      that pain. Participants reported that pain management was inadequate and that
      they developed their own strategies to respond to it. CONCLUSIONS: Pain continues
      to influence many patients' lives more than 1 year after a fragility fracture.
      Patient narratives could be useful to help health care providers to better
      recognize and manage this long-term consequence of fractures.

PMID- 29455248
TI  - Are there effects of age, gender, height, and body fat on the functional muscle
      bone unit in children and adults?
AB  - : The aim was to describe the effect of age, gender, height, different stages of
      human life, and body fat on the functional muscle-bone unit. All these factors
      had a significant effect on the functional muscle-bone unit and should be
      addressed when assessing functional muscle-bone unit in children and adults.
      INTRODUCTION: For the clinical evaluation of the functional muscle-bone unit, it
      was proposed to evaluate the adaptation of the bone to the acting forces. A
      frequently used parameter for this is the total body less head bone mineral
      content (TBLH-BMC) determined by dual-energy X-ray absorptiometry (DXA) in
      relation to the lean body mass (LBM by DXA). LBM correlates highly with muscle
      mass. Therefore, LBM is a surrogate parameter for the muscular forces acting in
      everyday life. The aim of the study was to describe the effect of age and gender
      on the TBLH-BMC for LBM and to evaluate the impact of other factors, such as
      height, different stages of human life, and of body fat. METHODS: As part of the
      National Health and Nutrition Examination Survey (NHANES) study, between the
      years 1999-2006 whole-body DXA scans on randomly selected Americans from 8 years
      of age were carried out. From all eligible DXA scans (1999-2004), three major US
      ethnic groups were evaluated (non-Hispanic Whites, non-Hispanic Blacks, and
      Mexican Americans) for further statistical analysis. RESULTS: For the statistical
      analysis, the DXA scans of 8190 non-Hispanic White children and adults (3903
      female), of 4931 non-Hispanic Black children and adults (2250 female) and 5421 of
      Mexican-American children and adults (2424 female) were eligible. Age, gender,
      body height, and especially body fat had a significant effect on the functional
      muscle-bone unit. CONCLUSIONS: When assessing TBLH-BMC for LBM in children and
      adults, the effects of age, gender, body fat, and body height should be
      addressed. These effects were analyzed for the first time in such a large cohort.

PMID- 29455249
TI  - Multiple vertebral fractures following osteoporosis treatment discontinuation: a
      case-report after long-term Odanacatib.
AB  - INTRODUCTION: Case reports of women sustaining multiple vertebral fractures (VF)
      soon afterdenosumab discontinuation are accumulating. METHODS: We report a woman
      with five new vertebral fractures in ~8 months following discontinuation of long
      term odanacatib (ODN), an experimental cathepsin K inhibitor. RESULTS: DXA
      examination demonstrated an ~12% decline in bone mineral density (BMD) and ~9%
      decline in trabecular bone score (TBS) since ODN discontinuation. Laboratory
      evaluation did not reveal a secondary cause of bone loss. CONCLUSIONS: This case
      mimics observations following denosumab discontinuation, but, to our knowledge,
      is the first reported with ODN and the first documenting substantial decline in
      TBS. While not directly clinically relevant as ODN is no longer being developed,
      this case raises the possibility that a syndrome of multiple vertebral fractures
      could follow discontinuation of various potent osteoporosis therapies that
      produce major BMD increases but do not have persisting bone effects (i.e., all
      non-bisphosphonates). Use of antiresorptive therapies to prevent rapid bone loss
      following discontinuation of potent bone active agents seems appropriate.
      Identification of those patients who could be at risk for the multiple VF
      syndrome is needed.

PMID- 29455250
TI  - Systematic review and meta-analysis of prevalence of sarcopenia in post acute
      inpatient rehabilitation.
AB  - : Sarcopenia is associated with poor function and increased risk of falls and
      disability. This work reports a systematic review and meta-analysis of prevalence
      of sarcopenia in post acute inpatient rehabilitation. Sarcopenia is found to be
      present in approximately 50% of rehabilitation patients and its prevalence may
      vary with admission diagnosis. PURPOSE: To conduct a systematic review and meta
      analysis of reported prevalence of sarcopenia in post acute inpatient
      rehabilitation. METHODS: Systematic review conducted according to PRISMA
      guidelines (PROSPERO registration number CRD42016054135). Databases searched
      MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central
      Register of Controlled Trials (CENTRAL), Cochrane Methodology Register, and
      CINAHL. Studies considered the following: published January 1988-February 2017.
      Key terms are as follows: "sarcopenia" AND "inpatient rehabilitation" OR
      "rehabilitation" AND/OR "prevalence". Abstracts and subsequently full studies
      reporting sarcopenia prevalence in adults admitted to rehabilitation reviewed
      irrespective of design, provided sarcopenia diagnosis included at least
      assessment of muscle mass. Random effect meta-analysis was conducted.
      Methodological quality assessment: Agency for Healthcare Research and Quality, US
      Department of Health and Human Services tool (MORE tool); Joanna Briggs Institute
      Prevalence Critical Appraisal Tool. RESULTS: Four hundred twenty-six studies
      identified during initial search, 399 excluded after reviewing titles and
      abstracts, 21 full text articles reviewed, and six studies met inclusion
      criteria. Patient populations: after hip fracture (five studies), general
      deconditioning (one study). Identified sarcopenia prevalence ranged from 0.28 to
      0.69. Pooled sarcopenia prevalence obtained with random effect meta-analysis:
      0.56 (95% CI 0.46-0.65), heterogeneity I2 = 92.9%. Main quality shortcomings:
      lack of reporting of inter- and intra-rater reliability, lack of generalizability
      to other rehabilitation populations. CONCLUSIONS: Original research examining
      sarcopenia prevalence in inpatient rehabilitation is scarce. Patient populations
      studied to date are not representative of general rehabilitation population with
      regard to both age and admission diagnoses. Sarcopenia may be present in
      approximately half of rehabilitation patients and its prevalence may vary with
      admission diagnosis.

PMID- 29455251
TI  - Establishing and characterizing lacrispheres from human lacrimal gland for
      potential clinical application.
AB  - PURPOSE: Lacrimal gland (LG) dysfunction leading to dry eye syndrome (DES) is an
      important cause of ocular morbidity. One of the potential and promising long-term
      management therapies for restoration of LG function could be transplantation of
      autologous ex vivo expanded stem cells. The present study was aimed at exploring
      the 2D and 3D cultures of human LG, identifying inherent stem cells and
      evaluating their secretory potential. METHODS: Fresh human lacrimal gland (HuLG)
      (n = 5) from patients undergoing therapeutic exenteration was harvested after
      ethical approval and informed consent. The gland was enzymatically digested and
      the isolated cells plated in Hepato-STIM media supplemented with l-glutamine,
      epidermal growth factor, fibroblast growth factor, and N-2 supplement. The native
      HuLG and the cultured spheres (DIV14-16) were evaluated for presence of stem
      cells (CD117 expression, quiescence, BrdU label retention, cell cycle, colony
      forming efficiency) and differentiation (secretion of tear proteins). RESULTS:
      Under the established culture conditions, suspension 3D cultures of human
      "lacrispheres" could be maintained and propagated for 3-4 weeks. The spheres
      consist of both acinar as well as ductal cells with evidence of stem cells (0.8
      +/- 0.05% CD117+ cells), BrdU label retention (9.31 +/- 0.41%), G0/G1 profile
      similar to native lacrimal cells at isolation (76.9 versus 79.9%) and colony
      forming units (3.1%). The lacrispheres also secreted quantifiable levels of tear
      proteins (lysozyme, lactoferrin, scIgA) into the conditioned media. CONCLUSION:
      The study provides promising, first-of-its-kind evidence for the generation of
      lacrispheres from fresh HuLG, with enriched population of stem cells and
      secretory competent differentiated cells. The dual properties of these spheres
      make them a highly suitable source of transplantable cells for restoring the
      structure and function of damaged lacrimal gland.

PMID- 29455252
TI  - The effect of anti-tumor necrosis factor alpha agents on the outcome in pediatric
      uveitis of diverse etiologies.
AB  - PURPOSE: This study aimed to report the clinical outcome of children with uveitis
      treated with anti-tumor necrosis factor alpha (TNF-alpha) agents. METHODS: This
      included a retrospective cohort study. Children with uveitis treated with
      infliximab or adalimumab in 2008-2014 at five dedicated uveitis clinics were
      identified by database search. Their medical records were reviewed for
      demographic data, clinical presentation, ocular complications, and visual
      outcome. Systemic side effects and the steroid-sparing effect of treatment were
      documented. RESULTS: The cohort included 24 patients (43 eyes) of whom 14
      received infliximab and 10 received adalimumab after failing conventional
      immunosuppression therapy. Mean age was 9.3 +/- 4.0 years. The most common
      diagnosis was juvenile idiopathic arthritis-related uveitis (n = 10), followed by
      Behcet's disease (n = 4), sarcoidosis (n = 1), and ankylosing spondylitis (n =
      1); eight had idiopathic uveitis. Ocular manifestations included panuveitis in 20
      eyes (46.5%), chronic anterior uveitis in 19 (44.2%), and intermediate uveitis in
      4 (9.3%). The duration of biologic treatment ranged from 6 to 72 months. During
      the 12 months prior to biologic treatment, while on conventional
      immunosuppressive therapy, mean visual acuity deteriorated from 0.22 to 0.45
      logMAR, with a trend of recovery to 0.25 at 3 months after initiation of biologic
      treatment, remaining stable thereafter. A full corticosteroid-sparing effect was
      demonstrated in 16 of the 19 patients (84.2%) for whom data were available.
      Treatment was well tolerated. CONCLUSIONS: Treatment of pediatric uveitis with
      anti-TNF-alpha agents may improve outcome while providing steroid-sparing effect,
      when conventional immunosuppression fails. The role of anti-TNF-alpha agents as
      first-line treatment should be further investigated in controlled prospective
      clinical trials.

PMID- 29455253
TI  - Incorporation of the fluoroless C-Arm Trainer at the American Urological
      Association hands on training percutaneous renal access.
AB  - OBJECTIVES: To assess for usefulness and validity evidence for incorporating the
      C-Arm Trainer (CAT) simulator into the annual AUA hands on course for training
      percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: The course started
      with a didactic session followed by four stations for training the "bull's eye"
      technique using the CAT simulator. Each station included a pre-test, 30-min
      practice on the simulator, and post-test. All participants were assessed using a
      4-item checklist. All participants were asked to fill in a qualitative self
      assessment questionnaire after the pre- and the post-test, and respond to a
      course evaluation questionnaire and post-course survey. RESULTS: A total of 38
      physicians, who attended the hands on course, voluntarily participated in the
      study. Only 21.1% had previous practice on PCNL simulators. Compared with the
      results of the checklist total score and the qualitative self-assessment
      questionnaire scores after the pre-test, there was significant improvement in the
      checklist total score (p < 0.001), temporal demands (p = 0.003), situational
      stress (p = 0.003, and performance (0.003) after the post-test. A total of 14
      (36%) participants responded to the course evaluation questionnaire, 50%
      evaluated the course as excellent, 28.6% as very good, and 21.4% as good.
      Unfortunately, only five (13%) participants responded to the post-course survey,
      4/5 implemented the new competencies and knowledge into their practice, and 3/5
      have attempted to obtain fluoroscopic guided PCA without assistance. CONCLUSION:
      The CAT simulator was considered useful for training the percutaneous renal
      access procedure. There was significant improvement in the qualitative and
      quantitative assessment parameters after the post-test compared with the pre
      test.

PMID- 29455254
TI  - Postpartum fatigue: assessing and improving the psychometric properties of the
      Fatigue Severity Scale.
AB  - A brief, reliable, and valid measure of postpartum fatigue in both clinical and
      research settings is much needed. This study assessed the psychometric properties
      of the Fatigue Severity Scale (FSS) among women with unsettled infants and
      fatigue. Rasch analysis identified an overall ceiling effect for the original
      FSS, as well as disordered response categories and/or poor fit for 4 items. A
      modified 5-item version of the FSS (FSS-5R) had improved psychometric properties.

PMID- 29455255
TI  - Fasting or Non-fasting Lipids for Atherosclerotic Cardiovascular Disease Risk
      Assessment and Treatment?
AB  - PURPOSE OF REVIEW: Dyslipidemia is a major modifiable risk factor for
      atherosclerotic cardiovascular disease (ASCVD); however, lipid testing for risk
      assessment and treatment surveillance has been underutilized. Several factors
      likely account for this, including the common practice of measuring lipid levels
      in the fasting state, which often necessitates that patients return for an
      additional visit. In this review, we evaluate potential advantages and cautions
      associated with measuring lipids in the non-fasting state. RECENT FINDINGS: There
      is similar performance with the use of either fasting or non-fasting total
      cholesterol and HDL cholesterol in ASCVD risk assessment. Observational studies
      demonstrate that in comparison to fasting levels, non-fasting triglycerides are
      approximately 20% higher on average, although the magnitude of difference is
      subject to substantial inter-patient variability. Higher triglycerides can lead
      to the under-estimation of low-density lipoprotein cholesterol (LDL-C) by
      approximately 10 mg/dL or more when calculated using the Friedewald equation.
      This is especially clinically relevant at low LDL-C levels, although a novel
      validated algorithm for LDL-C estimation largely overcomes this limitation. Non
      fasting lipid assessment is reasonable in many clinical circumstances given that
      ASCVD risk prediction is similar using fasting or non-fasting lipid values and
      because LDL-C can be accurately estimated using modern methods. Allowing the
      option for non-fasting lipid assessment can reduce a barrier to lipid testing and
      can facilitate a more convenient assessment of ASCVD risk with the ultimate
      potential effect of reducing the global burden of ASCVD. However, certain
      patients such as those with severe hypertriglyceridemias or high-risk patients
      being treated to low LDL-C levels may still need fasting lipid panels performed
      for precise diagnosis and to standardize therapeutic monitoring.

PMID- 29455256
TI  - Terrestrial-aquatic trophic linkages support fish production in a tropical
      oligotrophic river.
AB  - Despite low in situ primary productivity, tropical oligotrophic rivers support
      highly diverse fish assemblages and productive fisheries. This raises the
      question, what energy sources support fish production in these ecosystems? We
      sampled fish and food resources in the floodplain of a nearly pristine, large,
      oligotrophic river in western Amazonia. We combined data from stomach contents
      and stable isotopes to test the hypothesis that floodplain forests sustain
      fisheries in tropical oligotrophic rivers. Analysis of stomach contents from >
      800 specimens of 12 omnivorous fish species demonstrated that during the annual
      flood, forest plant matter dominated diets. Yet, our isotope mixing models
      estimated that arthropods from the forest canopy made a greater proportional
      contribution to fish biomass. Most of these arthropods are entirely terrestrial
      and, therefore, serve as trophic links between forests and fishes. Our results
      suggest that forest vegetation, particularly fruits, may provide much of the
      energy supporting metabolism and arthropods contribute significant amounts of
      protein for somatic growth. Moreover, the importance of terrestrial arthropods in
      support of fish biomass in oligotrophic rivers depends on interactions between
      riparian vegetation, terrestrial arthropods and flood pulse dynamics affecting
      accessibility of arthropods to fishes. The apparent paradox of high fish
      diversity in an oligotrophic river with low primary productivity may be
      explained, at least partially, by dynamic terrestrial-aquatic trophic linkages.
      This study further emphasizes the importance of seasonally flooded forests for
      sustaining fisheries in the Amazon.

PMID- 29455257
TI  - Finite element analysis of hollow out-of-plane HfO2 microneedles for transdermal
      drug delivery applications.
AB  - Transdermal drug delivery (TDD) based on microneedles is an excellent approach
      due to its advantages of both traditional transdermal patch and hypodermic
      syringes. In this paper, the fabrication method of hollow out-of-layer hafnium
      oxide (HfO2) microneedles mainly based on deep reactive ion etching of silicon
      and atomic layer deposition of HfO2 is described, and the finite element analysis
      of the microneedles based on ANSYS software is also presented. The fabrication
      process is simplified by using a single mask. The finite element analysis of a
      single microneedle shows that the flexibility of the microneedles can be easily
      adjusted for various applications. The finite element analysis of a 3 * 3 HfO2
      microneedle array applied on the skin well explains the "bed of nail" effect,
      i.e., the skin is not liable to be pierced when the density of microneedles in
      array increases. The presented research work here provides useful information for
      design optimization of HfO2 microneedles used for TDD applications.

PMID- 29455258
TI  - Effects of capsaicin on ovarian granulosa cell proliferation and apoptosis.
AB  - Capsaicin is the pungent ingredient in red peppers. Due to the effects on the
      sensory nerve fibers, capsaicin has been used to treat pain and inflammation
      associated with a variety of diseases including rheumatoid arthritis and diabetic
      neuropathy, obesity, and cardiovascular and gastrointestinal conditions. Despite
      the extensive publications on different systems, the studies of the effects on
      the ovary are very limited. The present study was conducted to examine the
      possible proliferative and/or apoptotic effects of various doses of capsaicin on
      primarily derived granulosa cells. In accordance with this purpose, ovarian
      granulosa cells were exposed to different doses of capsaicin for 24 and 48 h. The
      proliferative effects of capsaicin were examined by immunocytochemistry,
      immunofluorescence, and western blot using an antibody against proliferating cell
      nuclear antigen (PCNA) and cell viability assay (MTT). The effects on apoptosis
      were determined by immunocytochemistry and immunofluorescence using antibodies
      against cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP). We
      showed that the number of apoptotic cells increased in a capsaicin dose and time
      dependent manners. We found that a low dose of CAP in 24 h administration was
      more effective on granulosa cell proliferation. Our results suggest that low-dose
      and short-term administration of CAP may have a positive effect on ovarian
      folliculogenesis.

PMID- 29455259
TI  - Influence of Zn(II) stress-induction on component variation and sorption
      performance of extracellular polymeric substances (EPS) from Bacillus
      vallismortis.
AB  - Bacillus vallismortis (B. vallismortis), an aerobic heterotrophic bacteria, was
      screened in a laboratory pilot study, to assess the interaction between the heavy
      metal Zn(II) and extracellular polymeric substances (EPS). The influence of
      Zn(II) stress on EPS production, component variation, and sorption performance,
      was investigated. The characteristics of B. vallismortis EPS formed under stress
      were analyzed using FTIR, 3D-EEM and XPS. EPS was used as an adsorbent and the
      adsorption capacity and adsorption behavior of EPS formed with and without Zn(II)
      stress, were compared and assessed. Results showed that the production of
      polysaccharides and proteins, the main components of EPS, were promoted under
      Zn(II) stress. The types of EPS functional groups observed remained the same with
      and without heavy metal stress, but their concentrations were increased. Due to
      stress-induction, the adsorption capacity of Zn-EPS was significantly enhanced
      compared with the control-EPS. Specific EPS produced by B. vallismortis in the
      presence of Zn(II) stress, could have a wide range of potential applications,
      allowing optimization and improvement of the capacity of EPS to remove heavy
      metals from effluent.

PMID- 29455260
TI  - Performance Evaluation of State-of-the-Art Local Feature Detectors and
      Descriptors in the Context of Longitudinal Registration of Retinal Images.
AB  - In this paper we systematically evaluate the performance of several state-of-the
      art local feature detectors and descriptors in the context of longitudinal
      registration of retinal images. Longitudinal (temporal) registration facilitates
      to track the changes in the retina that has happened over time. A wide number of
      local feature detectors and descriptors exist and many of them have already
      applied for retinal image registration, however, no comparative evaluation has
      been made so far to analyse their respective performance. In this manuscript we
      evaluate the performance of the widely known and commonly used detectors such as
      Harris, SIFT, SURF, BRISK, and bifurcation and cross-over points. As of
      descriptors SIFT, SURF, ALOHA, BRIEF, BRISK and PIIFD are used. Longitudinal
      retinal image datasets containing a total of 244 images are used for the
      experiment. The evaluation reveals some potential findings including more
      robustness of SURF and SIFT keypoints than the commonly used bifurcation and
      cross-over points, when detected on the vessels. SIFT keypoints can be detected
      with a reliability of 59% for without pathology images and 45% for with pathology
      images. For SURF keypoints these values are respectively 58% and 47%. ALOHA
      descriptor is best suited to describe SURF keypoints, which ensures an overall
      matching accuracy, distinguishability of 83%, 93% and 78%, 83% for without
      pathology and with pathology images respectively.

PMID- 29455262
TI  - Spatio-temporal variability of physico-chemical variables, chlorophyll a, and
      primary productivity in the northern Arabian Sea along India coast.
AB  - The present study attempts to understand the seasonal and spatial variations in
      the physico-chemical (temperature, pH, salinity, dissolved oxygen, and nutrients)
      and productivity characteristics of the northern Arabian Sea off the Indian
      coast. Samples were collected from four different sites off the Veraval coast.
      The values of the physical and chemical variables were higher during the summer
      season, whereas nutrient concentrations were high during the winter season due to
      the maturity of intake nutrients during post-monsoon and winter convective mixing
      during the northeast monsoon. The dissolved oxygen (DO) concentration was
      strongly and positively correlated with the net primary productivity (NPP) and
      chlorophyll a (Chl-a) content to support productivity along the region.
      Dissimilarity in study variables was observed between the inshore and offshore
      locations. Principal component analysis revealed a strong relationship between
      nutrients and productivity variables (Chl-a and NPP). Nutrient levels were high
      at inshore sites, which can be attributed to the heavy nutrient load from land
      based anthropogenic activities and impact due to natural processes like water
      mixing, sedimentation, and wave activities. Nutrients were strongly and
      positively correlated with the productivity variables, i.e., Chl-a and NPP. Chl-a
      positively correlated with NPP (r = 0.90), which indicates that it is a principle
      productivity pigment in the marine ecosystem.

PMID- 29455261
TI  - Phytoglobins regulate nitric oxide-dependent abscisic acid synthesis and ethylene
      induced program cell death in developing maize somatic embryos.
AB  - MAIN CONCLUSION: During maize somatic embryogenesis, suppression of phytoglobins
      (Pgbs) reduced ABA levels leading to ethylene-induced programmed cell death in
      the developing embryos. These effects modulate embryonic yield depending on the
      cellular localization of specific phytoglobin gene expression. Suppression of Zea
      mays phytoglobins (ZmPgb1.1 or ZmPgb1.2) during somatic embryogenesis induces
      programmed cell death (PCD) by elevating nitric oxide (NO). While ZmPgb1.1 is
      expressed in many embryonic domains and its suppression results in embryo
      abortion, ZmPgb1.2 is expressed in the basal cells anchoring the embryos to the
      embryogenic tissue. Down-regulation of ZmPgb1.2 is required to induce PCD in
      these anchor cells allowing the embryos to develop further. Exogenous
      applications of ABA could reverse the effects caused by the suppression of either
      of the two ZmPgbs. A depletion of ABA, ascribed to a down-regulation of
      biosynthetic genes, was observed in those embryonic domains where the respective
      ZmPgbs were repressed. These effects were mediated by NO. Depletion in ABA
      content increased the transcription of genes participating in the synthesis and
      response of ethylene, as well as the accumulation of ethylene, which influenced
      embryogenesis. Somatic embryo number was reduced by high ethylene levels and
      increased with pharmacological treatments suppressing ethylene synthesis. The
      ethylene inhibition of embryogenesis was linked to the production of reactive
      oxygen species (ROS) and the execution of PCD. Integration of ABA and ethylene in
      the ZmPgb regulation of embryogenesis is proposed in a model where NO accumulates
      in ZmPgb-suppressing cells, decreasing the level of ABA. Abscisic acid inhibits
      ethylene biosynthesis and the NO-mediated depletion of ABA relieves this
      inhibition causing ethylene to accumulate. Elevated ethylene levels trigger
      production of ROS and induce PCD. Ethylene-induced PCD in the ZmPgb1.1
      suppressing line [ZmPgb1.1 (A)] leads to embryo abortion, while PCD in the
      ZmPgb1.2-suppressing line [ZmPgb1.2 (A)] results in the elimination of the anchor
      cells and the successful development of the embryos.

PMID- 29455263
TI  - Halobacterium salinarum storage and rehydration after spray drying and
      optimization of the processes for preservation of carotenoids.
AB  - Spray drying is appropriate for the preservation of halophilic microorganisms due
      to the nature of these microorganisms, as they survive in adverse environmental
      conditions by being encapsulated in salt crystals. Artificial neural networks
      were in this study used to optimize practically significant spray-drying regimes
      of the C50-carotenoids producer Halobacterium salinarum. Immediately after
      drying, the samples contained up to 54% halobacterial biomass and less than 5%
      moisture, and the level of preservation of carotenoids was 95-97%. The storage of
      biomass at 4  degrees C resulted in the gradual degradation of the carotenoids,
      which reached 58-64% in the best samples after 1 year. A comprehensive study of
      changes in halobacteria biomass after spray drying and the nature of the damage
      provided new data on the survival and preservation of cells and biologically
      active substances in the various spray-drying regimes and at different storage
      times.

PMID- 29455264
TI  - Mortality Rate and Predictors in Children Under 15 Years Old Who Acquired HIV
      from Mother to Child Transmission in Paraguay.
AB  - We estimated mortality rate and predictors of death in children and adolescents
      who acquired HIV through mother-to-child transmission in Paraguay. In 2000-2014,
      we conducted a cohort study among children and adolescents aged < 15 years. We
      abstracted data from medical records and death certificates. We used the Cox
      proportional hazards model for the multivariable analysis of mortality
      predictors. A total of 302 subjects were included in the survey; 216 (71.5%) were
      younger than 5 years, 148 (51.0%) were male, and 214 (70.9%) resided in the
      Asuncion metropolitan area. There were 52 (17.2%) deaths, resulting in an overall
      mortality rate of 2.06 deaths per 100 person-years. The children and adolescents
      with hemoglobin levels <= 9 g/dL at baseline had a 2-times higher hazard of death
      compared with those who had levels > 9 g/dL (HR 2.27, 95% CI 1.01-5.10). The
      mortality of HIV-infected children and adolescents in Paraguay is high, and
      anemia is associated with mortality. Improving prenatal screening to find cases
      earlier and improving pediatric follow-up are needed.

PMID- 29455265
TI  - Grit and Ambition are Associated with Better Neurocognitive and Everyday
      Functioning Among Adults Living with HIV.
AB  - Grit and ambition are psychological factors that may protect neurocognitive
      function among persons living with HIV (PLWH). We examined associations between
      grit, ambition, premorbid verbal intellectual function, and current
      neurocognitive and everyday functioning among PLWH and persons without HIV (HIV
      ). 120 PLWH and 94 HIV- adults completed the Grit Scale (includes total score and
      consistency of interests and perseverance of effort subscales), ambition scale,
      and a comprehensive neurobehavioral battery. PLWH had lower grit scores than HIV-
      adults. The two groups did not differ on ambition. No relationship was observed
      between grit and cognition among HIV- adults. Among PLWH, however, higher
      perseverance of effort and more ambition was related to better global
      neurocognitive functioning, and higher grit, but not ambition, was related to
      independence in daily functioning. Longitudinal studies are needed to elucidate
      these relationships over time and examine whether grit or ambition have
      protective effects on cognitive outcomes among PLWH.

PMID- 29455266
TI  - Inflammatory tenosynovitis and enthesitis induced by immune checkpoint inhibitor
      treatment.
AB  - Reports about immune-related adverse events (IrAEs) induced by immune checkpoint
      inhibitors (ICIs) have been increasing. Although the importance of understanding
      joint involvement and myalgia as an IrAE has grown, little is known about its
      characteristics. The aim of this study was to investigate the incidence and
      clinical characteristics of articular IrAEs. We reviewed 133 patients who were
      treated with ICIs in our institution and referred to our rheumatologic. Among
      them, 2 (1.5%) developed arthritis during the use of anti-PD-1 inhibitor, and
      there was one patient with joint pain after anti-PD-L1 inhibitor who was referred
      to our department from another institution. No patients had antecedent
      inflammatory arthritis or any relevant medical history. All 3 patients were
      negative for anti-nuclear antibody, rheumatoid factor, and anti-cyclic
      citrullinated peptide antibody. The ultrasonography showed tenosynovitis and
      enthesitis in both small and large joints with no or insignificant synovitis.
      Joint pain improved gradually within 6 months with only NSAIDs in 2 patients, and
      disappeared quickly in the other patient 2 weeks after 20 mg/day of
      predonisolone. Our report suggested diverse phenotypes of joint involvement and
      highlighted the importance of accumulating such patients.

PMID- 29455267
TI  - Reactive arthritis: update 2018.
AB  - At this time, reactive arthritis (ReA) is considered to be part of the spectrum
      of the spondyloarthritis, previously known as Reiter's syndrome, and refers to an
      infection induced systemic illness, characterized by a sterile synovitis
      occurring in a genetically predisposed individual, secondary to an infection
      localized in a distant organ/system, but also accompanied with multiple extra
      articular manifestations.

PMID- 29455268
TI  - Family history of cancer in first-degree relatives and risk of gastric cancer and
      its precursors in a Western population.
AB  - BACKGROUND: Family history may inform risks of gastric cancer and preneoplastic
      lesions. METHODS: We examined associations with history of cancer in first-degree
      relatives for 307 incident gastric cancer cases among 20,720 male smokers in a
      prospective study in Finland. Cox regression was used to calculate gastric cancer
      hazard ratios (HR) and 95% confidence intervals (95% CI). Logistic regression was
      used to estimate odds ratios (OR) and 95% CIs for low serum pepsinogen, a marker
      of gastric atrophy. RESULTS: Gastric cancer risk was associated with gastric
      cancer history in first-degree relatives overall (HR 1.56, 95% CI 1.15-2.12), in
      fathers (HR 1.67, 95% CI 1.09-2.55) and in siblings (HR 2.05, 95% CI 1.25-3.38).
      Associations were significant for noncardia (HR 1.83, 95% CI 1.30-2.57) but not
      cardia (HR 0.93, 95% CI 0.46-1.87) cancers, and marginal for both intestinal-(HR
      1.53, 95% CI 0.92-2.55) and diffuse-type (HR 1.47, 95% CI 0.72-3.03) histologies.
      Family history of other cancer types was not associated with gastric cancer risk.
      Family history of gastric cancer was associated with low pepsinogen (OR 1.29, 95%
      CI 1.11-1.50). CONCLUSIONS: Family history of gastric cancer is strongly
      associated with specific subtypes of gastric cancer as well as with gastric
      atrophy, a risk factor for developing this malignancy.

PMID- 29455270
TI  - Ventricular Tachycardia Triggered by Loperamide and Famotidine Abuse.
AB  - A 32-year-old male developed recurrent ventricular tachycardia after taking mega
      doses of loperamide and famotidine in order to experience an opiate-like euphoric
      effect. He was taking up to 200 mg of loperamide and multiple doses of famotidine
      each day. He developed palpitations and syncope. Electrocardiography demonstrated
      ventricular tachycardia and QT interval prolongation (corrected QT interval was
      597 ms). He was diagnosed with loperamide-induced QT prolongation resulting in
      incessant ventricular tachycardia. Loperamide was discontinued, and he was
      treated with electrolyte replacement, supportive care, and monitoring. After 5
      days, his electrocardiogram (ECG) normalized and he had no more ventricular
      tachycardia. A Naranjo assessment score of 8 was obtained, indicating a probable
      relationship between QT prolongation and his use of loperamide. Large doses of
      loperamide can cause QT interval prolongation and life-threatening arrhythmias.
      These effects may be accentuated when histamine-2 receptor blockers are also
      abused.

PMID- 29455269
TI  - The efficacy and safety of targeted therapy with or without chemotherapy in
      advanced gastric cancer treatment: a network meta-analysis of well-designed
      randomized controlled trials.
AB  - BACKGROUND: Advanced gastric cancer (AGC) is a severe malignant tumor associated
      with high mortality. Targeted therapy is an important approach for improving the
      therapeutic effects of AGC treatment. This study evaluates the efficacy and
      safety of targeted agents for AGC patients. METHODS: PubMed, EmBase, and the
      Cochrane Library were searched for double-blind randomized controlled trials
      (RCTs) of AGC treatments published prior to July 2017. Progression-free survival
      (PFS), overall survival (OS), objective response rate (ORR), and severe adverse
      effects (AEs) were evaluated to determine the efficacy and safety of targeted
      agents. A network meta-analysis with a frequentist framework was performed to
      assess the effects of various targeted agents for AGC treatment. RESULTS: Our
      analysis included 16 articles involving 5371 patients and 11 types of agents. The
      network meta-analysis showed that apatinib (97.5%) was most likely to improve
      PFS, followed by regorafenib (86.3%) and rilotumumab (65.4%). Apatinib was
      similarly best for OS outcome, (95.5%) followed by rilotumumab (74.7%) and
      regorafenib (70%). Apatinib (89.6%) also had the best improvement on ORR,
      followed by rilotumumab (75.4%) and everolimus (68.4%). Bevacizumab (85.5%) was
      likely to get the lowest severe AEs, followed by sunitinib (63%). CONCLUSIONS:
      Apatinib, regorafenib, and rilotumumab improved patient PFS and OS. When combined
      with chemotherapy, ramucirumab and rilotumumab had high efficacy but low
      tolerability, and bevacizumab had moderate efficacy and tolerability for PFS.
      Without chemotherapy, ramucirumab and regorafenib had relatively high therapeutic
      efficacy tolerability for PFS.

PMID- 29455271
TI  - Progressive Supranuclear Palsy: an Update.
AB  - PURPOSE OF REVIEW: Progressive supranuclear palsy (PSP) is a 4R tau
      neuropathologic entity. While historically defined by the presence of a vertical
      supranuclear gaze palsy and falls in the first symptomatic year,
      clinicopathologic studies identify alternate presenting phenotypes. This article
      reviews the new PSP diagnostic criteria, diagnostic approaches, and treatment
      strategies. RECENT FINDINGS: The 2017 International Parkinson and Movement
      Disorder Society PSP criteria outline 14 core clinical features and 4 clinical
      clues that combine to diagnose one of eight PSP phenotypes with probable,
      possible, or suggestive certainty. Evidence supports the use of select imaging
      approaches in the classic PSP-Richardson syndrome phenotype. Recent trials of
      putative disease-modifying agents showed no benefit. The new PSP diagnostic
      criteria incorporating the range of presenting phenotypes have important
      implications for diagnosis and research. More work is needed to understand how
      diagnostic evaluations inform phenotype assessment and identify expected
      progression. Current treatment is symptomatic, but tau-based therapeutics are in
      active clinical trials.

PMID- 29455272
TI  - The outcome and timing of death of 17,767 nosocomial bloodstream infections in
      acute care hospitals in Finland during 1999-2014.
AB  - Few studies covering all patient groups and specialties are available regarding
      the outcome of nosocomial bloodstream infections (BSI). We analyzed the role of
      patient characteristics and causative pathogens of nosocomial BSIs reported by
      the hospitals participating in national surveillance in Finland during 1999-2014,
      in terms of outcome, with particular interest in those leading to death within 2
      days (i.e. early death). National nosocomial BSI surveillance was laboratory
      based and hospital-wide. Data on nosocomial BSIs was collected by infection
      control nurses, and dates of death were obtained from the national population
      registry with linkage to national identity codes. A total of 17,767 nosocomial
      BSIs were identified; 557 BSIs (3%) were fatal within 2 days and 1150 (6%) within
      1 week. The 1-month case fatality was 14% (2460 BSIs), and 23% of the deaths
      occurred within 2 days and 47% within 1 week. The patients who died early were
      older than those who survived > 28 days, and their BSIs were more often related
      to intensive care. Gram-positive bacteria caused over half of the BSIs of
      patients who survived, whereas gram-negative bacteria, especially Pseudomonas
      aeruginosa, caused more often BSIs of patients who died early, and fungi BSIs of
      patients who died within 1 week. A significant portion of patients with
      nosocomial BSIs died early, which underlines the importance of rapid recognition
      of BSI. Hospital-wide surveillance data of causative pathogens can be utilized
      when composing recommendations for empiric antimicrobial treatment in
      collaboration with clinicians, as well as when promoting infection prevention.

PMID- 29455273
TI  - Updates on Device-Based Therapies for Patients with Heart Failure.
AB  - PURPOSE OF REVIEW: Heart failure is a growing epidemic. Optimal medical therapy
      remains the cornerstone of heart failure management but device-based therapies
      have been shown to contribute to morbidity and mortality reduction. RECENT
      FINDINGS: Multiple investigational trials had been conducted in the past decade
      that helped us better understand and manage heart failure. In this manuscript, we
      will discuss the major device related trials of year 2017 in the fields of
      defibrillators, hemodynamic monitoring, remote monitoring, autonomic nervous
      system modulation, ventricular assist devices, and device-based valvular heart
      disease management. Further research and trials in device-based therapies are
      needed to explore their long-term reduction in mortality and morbidity along with
      cost-effectiveness analyses in patients living with heart failure.

PMID- 29455274
TI  - Platelet-rich plasma in the management of Asherman syndrome: case report.

PMID- 29455275
TI  - The effect of different levels of dietary restriction on glucose homeostasis and
      metabolic memory.
AB  - Over the past 50 years, dietary restriction (DR) has been shown to extend the
      life span of a wide variety of organisms. A hallmark feature of DR is improved
      glucose homeostasis resulting in increased glucose tolerance and insulin
      sensitivity of animals ranging from rodents to humans. In this study, we
      demonstrate the early effects of varying levels of DR on glucose tolerance.
      Within 10 days of 40% DR, glucose tolerance was significantly improved and by 120
      days; 10 and 20% DR also showed enhanced glucose tolerance. All three levels of
      DR showed reduced adiposity, increased expression of genes involved in fat
      turnover, and a reduction in the expression for markers of inflammation. Studies
      have shown that mice fed a DR diet retained metabolic memory in terms of improved
      glucose tolerance even after DR is discontinued. We show that 40% DR not only has
      an early effect on glucose tolerance but also maintained it after DR was
      discontinued for 2 months. Therefore, improvement in glucose tolerance is brought
      about by all three levels of DR but the metabolic memory is not dose responsive.

PMID- 29455276
TI  - Methylation of secreted frizzled-related protein 1 (SFRP1) promoter downregulates
      Wnt/beta-catenin activity in keloids.
AB  - Keloid, a benign skin disorder, forms during wound healing in genetically
      susceptible individuals. To better control keloid and understand the molecular
      mechanisms, this study screened gene hypermethylations of GEO database microarray
      data on keloids and identified the hypermethylation of the secreted frizzled
      related protein-1 (SFRP1) promoter. Subsequently, hypermethylation and mRNA and
      protein levels were assessed in 57 cases of keloid vs. normal skin tissues.
      Fibroblasts from tissues were isolated for the assessment of gene regulation in
      vitro. The methods used were bioinformatic analysis, lentiviral infection
      carrying SFRP1 cDNA, qRT-PCR, western blot, immunohistochemistry, luciferase
      reporter assay, methylation-specific PCR and methylated DNA immunoprecipitation
      qPCR, ELISA, and/or 5-Aza-2'-deoxycytidine treatment. The data revealed that the
      SFRP1 promoter was hypermethylated in keloid tissues, compared with that in
      normal skin tissues. The SFRP1 promoter methylation contributed to the
      downregulation of SFRP1 mRNA and protein in keloid tissues and keloid
      fibroblasts. The 5-Aza treatment significantly upregulated SFRP1 mRNA and protein
      level in keloid fibroblasts. Furthermore, the knockdown of DNMT1 expression, and
      not the expression of DNMT3a or DMNT3b, was responsible for the hypermethylation
      of the SFRP1 promoter and upregulation of SFRP1 mRNA and protein in keloid
      fibroblasts. In addition, the infection of lentivirus carrying SFRP1 cDNA
      significantly inhibited the signaling activity of Wnt/beta-catenin and the mRNA
      and protein expression of beta-catenin and alpha-SMA in keloid fibroblasts. In
      summary, the lost SFRP1 expression-induced Wnt/beta-catenin signaling due to the
      hypermethylation of the SFRP1 promoter could associate with keloid development,
      suggesting that SFRP1 might be a therapeutic target for keloid treatment.

PMID- 29455277
TI  - Guava (Psidium guajava L. cv. Red Suprema) Crude Extract Protect Human Dermal
      Fibroblasts against Cytotoxic Damage Mediated by Oxidative Stress.
AB  - We analyzed guava fruits (Psidium guajava L. cv. Red Suprema) from Cuba to
      determine their chemical composition, total antioxidant capacity, as well as
      their protective effect against oxidative damage using an in vitro model of human
      dermal fibroblasts. The guava fruit is a natural source of bioactive compounds,
      such as polyphenols, vitamin C, folates and beta carotenes with proven health
      benefits. Human dermal fibroblasts were pre-incubated with different
      concentrations of guava crude extract and then subjected to oxidative stress
      using the AAPH stressor. The number of apoptotic and dead cells, as well as the
      markers of oxidative damage such as lipid and protein oxidation significantly
      decreased when cells were pre-incubated with guava crude extract and then exposed
      to the stressor. The activity of antioxidant enzymes also improved when cells
      were pre-incubated with guava crude extract in comparison to cells subjected to
      stress without prior pre-incubation with the guava extract. The results obtained
      in this study highlight the health benefits of guava regarding oxidative stress,
      proving it to be an important source of bioactive compounds associated with
      important biological properties.

PMID- 29455278
TI  - A review of the design and modification of lactoferricins and their derivatives.
AB  - Lactoferricin (Lfcin), a multifunction short peptide with a length of 25
      residues, is derived from the whey protein lactoferrin by acidic pepsin
      hydrolysis. It has potent nutritional enhancement, antimicrobial, anticancer,
      antiviral, antiparasitic, and anti-inflammatory activities. This review describes
      the research advantages of the above biological functions, with attention to the
      molecular design and modification of Lfcin. In this examination of design and
      modification studies, research on the identification of Lfcin active derivatives
      and crucial amino acid residues is also reviewed. Many strategies for Lfcin
      optimization have been studied in recent decades, but we mainly introduce
      chemical modification, cyclization, chimera and polymerization of this peptide.
      Modifications such as incorporation of D-amino acids, acetylation and/or
      amidation could effectively improve the activity and stability of these
      compounds. Due to their wide array of bio-functions and applications, Lfcins have
      great potential to be developed as biological agents with multiple functions
      involved with nutritional enhancement, as well as disease preventive and
      therapeutic effects.

PMID- 29455279
TI  - Divergent Selection of Pattern Recognition Receptors in Mammals with Different
      Ecological Characteristics.
AB  - Pattern recognition receptors (PRRs) are specialized receptors that represent a
      key component of the host innate immune system. Whether molecular evolutionary
      history of different PRR classes have involved different genetic mechanisms
      underlying diverse pathogen environment in mammals, and whether distinct ecology
      of mammals may have imposed divergent selective pressures on the evolution of the
      PRRs, remained unknown. To test these hypotheses, we investigated the
      characterization of 20 genes belonging to four PRR classes in mammals. Evidence
      of positive selection was found in most (17 of 20) PRR genes examined, and most
      positively selected sites (84%) undergoing radical changes were found to fall in
      important functional regions, consistent with the co-evolutionary dynamics
      between the hosts and their microbial counterparts. We found different
      evolutionary patterns in different PRR classes, with the highest level of
      positive selection in C-type lectin receptor (CLR) family, suggesting that the
      capability of CLRs in response to a wide variety of ligands might explain their
      malleability to selection pressures. Tests using branch models that partitioned
      the data along habitat and social behavior found significant evidence of
      divergent selective pressures of PRRs among mammalian groups. Interestingly,
      species-specific evolution was detected on RIG-I-like helicase genes (RLRs) in
      cetaceans, suggesting that RLRs might play a critical role in the defense against
      widespread marine RNA viruses during their divergence and radiation into marine
      habitats. This study provides a comprehensive look at the evolutionary patterns
      and implications of mammalian PRRs, and highlights the importance of ecological
      influences in molecular adaptation.

PMID- 29455280
TI  - A novel integrated strategy for the detection and quantification of the
      neurotoxin beta-N-methylamino-L-alanine in environmental samples.
AB  - We describe a set of new tools for the detection and quantification of beta-N
      methylamino-L-alanine (BMAA) which includes a novel stable isotope-labeled BMAA
      standard (13C3,15N2) and a chip-based capillary electrophoresis mass spectrometry
      platform for separation and detection. Baseline resolution of BMAA from its
      potentially confounding structural isomers N-2-aminoethylglycine (AEG) and 2,4
      diaminobutyric acid (2,4-DAB) is achieved using the chip-based CE-MS system in
      less than 1 min. Detection and linearity of response are demonstrated across >
      3.5 orders of dynamic range using parallel reaction monitoring (PRM). The lower
      limit of detection and quantification were calculated for BMAA detection at 40 nM
      (4.8 ng/mL) and 400 nM (48 ng/mL), respectively. Finally, the strategy was
      applied to detect BMAA in seafood samples purchased at a local market in Raleigh,
      NC where their harvest location was known. BMAA was detected in a sea scallop
      sample. Because the BMAA/stable isotope-labeled 13C3,15N2-BMAA (SIL-BMAA) ratio
      in the scallop sample was below the limit of quantification, a semiquantitative
      analysis of BMAA content was carried out, and BMAA content was estimated to be
      approximately 820 ng BMAA/1 g of wet scallop tissue. Identification was verified
      by high mass measurement accuracy of precursor (< 5 ppm) and product ions (< 10
      ppm), comigration with SIL-BMAA spike-in standard, and conservation of ion
      abundance ratios for product ions between BMAA and SIL-BMAA. Interestingly, BMAA
      was not identified in the free protein fraction but only detected after protein
      hydrolysis which suggests that BMAA is tightly bound by and/or incorporated into
      proteins. Graphical abstract Utilization of novel 13C3,15N2-BMAA and chip-based
      CE-MS/MS for detection and quantification of BMAA in environmental samples.

PMID- 29455281
TI  - Sensitive colorimetric assay for uric acid and glucose detection based on
      multilayer-modified paper with smartphone as signal readout.
AB  - In this work, a multilayer-modified paper-based colorimetric sensing platform
      with improved color uniformity and intensity was developed for the sensitive and
      selective determination of uric acid and glucose with smartphone as signal
      readout. In detail, chitosan, different kinds of chromogenic reagents, and
      horseradish peroxidase (HRP) combined with a specific oxidase, e.g., uricase or
      glucose oxidase (GOD), were immoblized onto the paper substrate to form a
      multilayer-modified test paper. Hydrogen peroxide produced by the oxidases
      (uricase or GOD) reacts with the substrates (uric acid or glucose), and could
      oxidize the co-immoblized chromogenic reagents to form colored products with HRP
      as catalyst. A simple strategy by placing the test paper on top of a light
      emitting diode lamp was adopted to efficiently prevent influence from the
      external light. The color images were recorded by the smartphone camera, and then
      the gray values of the color images were calculated for quantitative analysis.
      The developed method provided a wide linear response from 0.01 to 1.0 mM for uric
      acid detection and from 0.02 to 4.0 mM for glucose detection, with a limit of
      detection (LOD) as low as 0.003 and 0.014 mM, respectively, which was much lower
      than for previously reported paper-based colorimetric assays. The proposed assays
      were successfully applied to uric acid and glucose detection in real serum
      samples. Furthermore, the enhanced analytical performance of the proposed method
      allowed the non-invasive detection of glucose levels in tear samples, which holds
      great potential for point-of-care analysis. Graphical abstract ?.

PMID- 29455282
TI  - Molecularly imprinted vs. reversed-phase extraction for the determination of
      zearalenone: a method development and critical comparison of sample clean-up
      efficiency achieved in an on-line coupled SPE chromatography system.
AB  - Sample preparation prior to chromatographic separation plays an important role in
      the analytical process. To avoid time-consuming and manual handling sample-prep,
      automated on-line techniques such as on-line SPE-HPLC are therefore preferred. In
      this study, two different on-line extraction approaches for mycotoxin/endocrine
      disruptor zearalenone (ZEA) determination using either molecularly imprinted
      polymer (MIP) with selective cavities and binding sites for extraction or a
      reversed-phase sorbent C18 providing non-selective interactions have been
      developed, validated, and compared. The validation characteristics were compared
      and the two methods were evaluated as being almost equal in terms of linearity,
      repeatability, precision, and recovery. Recoveries were in the range of 99.0
      100.1% and limits of detection were found the same for both methods (1.5 MUg L
      1). Method precision calculated for spiked beer samples was better for C18
      sorbent (2.5 vs. 5.4% RSD). No significant differences in the selectivity of
      either extraction method were observed. The possible reasons and further details
      associated with this finding are discussed. Finally, both validated methods were
      applied for the determination of ZEA contamination in beer samples. Due to ZEA's
      native fluorescence, chromatographic separation with fluorimetric detection
      (lambdaex = 270 nm and lambdaem, = 458 nm) was selected. Graphical abstract
      Determination of zearalenone in beer using an on-line extraction chromatography
      system.

PMID- 29455283
TI  - Utilizing hyaluronic acid as a versatile platform for fluorescence resonance
      energy transfer-based glucose sensing.
AB  - Here, we utilized the ultrasonic emulsification technique to generate hyaluronic
      acid microspheres incorporating a fluorescence-based glucose biosensor. We
      synthesized a novel lanthanide ion luminophore based on Eu3+. Eu
      sulfosuccinimidyl dextran (Eu-dextran) and Alexa Fluor 647 sulfosuccinimidyl-ConA
      (Alexa Fluor 647-ConA) were encapsulated in hyaluronic acid hydrogel to generate
      microspheres. Glucose sensing was carried out using a fluorescence resonance
      energy transfer (FRET)-based assay principle. A proportional fluorescence
      intensity increase was found within a 0.5-10-mM glucose concentration range. The
      glucose-sensing strategy showed an excellent tolerance for potential
      interferents. Meanwhile, the fluorescent signal of hyaluronic acid microspheres
      was very stable after testing for 72 h in glucose solution. Overall, hyaluronic
      acid microspheres encapsulating sensing biomolecules offer a stable and
      biocompatible biosensor for a variety of applications including cell culture
      systems, tissue engineering, detection of blood glucose, etc. Graphical abstract
      We report an ingenious biosensor encapsulated in hyaluronic acid microspheres for
      monitoring of glucose. Glucose sensing is carried out using a fluorescence
      resonance energy transfer-based assay principle with a novel lanthanide ions
      luminophore. The glucose detection system has excellent biocompatibility and
      stability for monitoring of glucose.

PMID- 29455284
TI  - Speciation analysis of arsenic in seafood and seaweed: Part I-evaluation and
      optimization of methods.
AB  - Several extraction and chromatographic methods were evaluated to identify optimum
      conditions for arsenic speciation analysis in seafood and seaweed. The extraction
      systems, which include aqueous, aqueous-organic, acidic, basic, and enzymatic
      solutions, were examined for their efficiency in extracting arsenic from finfish,
      crustaceans, molluscs, and seaweed keeping the chemical forms of the native
      arsenicals intact. While dilute solutions of nitric acid, hydrochloric acid, and
      tetramethylammonium hydroxide (TMAH) extract high fractions of arsenic from most
      of the matrices, the extractants oxidized arsenite (As3+) to arsenate (As5+) and
      converted some arsenosugars and non-polar arsenicals to known and/or unknown
      forms. Hot water (90  degrees C) effectively maintained the integrity of the
      native arsenic species and enabled analysis of the extracts with no further
      manipulation than filtration and dilution. Stepwise extraction of water-soluble
      and non-polar arsenic with hot water and a mixture of dichloromethane and
      methanol, respectively, resulted in sufficiently quantitative (> 75%) arsenic
      extraction from seafood and seaweed. Anion and cation exchange chromatographic
      methods were optimized for separation and quantitation of the arsenicals
      extracted into hot water. The non-polar arsenicals were collectively determined
      after digesting the extract in acid. The application of the optimum extraction
      and chromatographic conditions was demonstrated by analyzing certified reference
      materials of tuna fish tissue (BCR 627), lobster hepatopancreas (TORT-2) and
      oyster tissue (SRM 1566b), and a sample of hijiki seaweed. For all the matrices,
      good agreement (80-92%) was found between the total water-soluble arsenic and the
      sum of the concentrations of the chromatographed species. Limits of
      quantification (LOQ) were in the range 4-11 ng g-1 for 16 arsenicals.

PMID- 29455285
TI  - Characterization of a novel miniaturized burst-mode infrared laser system for IR
      MALDESI mass spectrometry imaging.
AB  - Laser systems are widely used in mass spectrometry as sample probes and
      ionization sources. Mid-infrared lasers are particularly suitable for analysis of
      high water content samples such as animal and plant tissues, using water as a
      resonantly excited sacrificial matrix. Commercially available mid-IR lasers have
      historically been bulky and expensive due to cooling requirements. This work
      presents a novel air-cooled miniature mid-IR laser with adjustable burst-mode
      output and details an evaluation of its performance for mass spectrometry
      imaging. The miniature laser was found capable of generating sufficient energy
      for complete ablation of animal tissue in the context of an IR-MALDESI experiment
      with exogenously added ice matrix, yielding several hundred confident metabolite
      identifications. Graphical abstract The use of a novel miniature 2.94 MUm burst
      mode laser in IR-MALDESI allows for rapid and sensitive mass spectrometry imaging
      of a whole mouse.

PMID- 29455286
TI  - Prediction of biotransformation products of the fungicide fluopyram by
      electrochemistry coupled online to liquid chromatography-mass spectrometry and
      comparison with in vitro microsomal assays.
AB  - Biotransformation processes of fluopyram (FLP), a new succinate dehydrogenase
      inhibitor (SDHI) fungicide, were investigated by electrochemistry (EC) coupled
      online to liquid chromatography (LC) and electrospray mass spectrometry (ESI-MS).
      Oxidative phase I metabolite production was achieved using an electrochemical
      flow-through cell equipped with a boron-doped diamond (BDD) electrode. Structural
      elucidation and prediction of oxidative metabolism pathways were assured by
      retention time, isotopic patterns, fragmentation, and accurate mass measurements
      using EC/LC/MS, LC-MS/MS, and/or high-resolution mass spectrometry (HRMS). The
      results obtained by EC were compared with conventional in vitro studies by
      incubating FLP with rat and human liver microsomes (RLM, HLM). Known phase I
      metabolites of FLP (benzamide, benzoic acid, 7-hydroxyl, 8-hydroxyl, 7,8
      dihydroxyl FLP, lactam FLP, pyridyl acetic acid, and Z/E-olefin FLP) were
      successfully simulated by EC/LC/MS. New metabolites including an imide, hydroxyl
      lactam, and 7-hydroxyl pyridyl acetic acid oxidative metabolites were predicted
      for the first time in our study using EC/LC/MS and liver microsomes. We found
      oxidation by dechlorination to be one of the major metabolism mechanisms of FLP.
      Thus, our results revealed that EC/LC/MS-based metabolic elucidation was more
      advantageous on time and cost of analysis and enabled matrix-free detection with
      valuable information about the mechanisms and intermediates of metabolism
      processes. Graphical abstract Oxidative metabolism of fluopyram.

PMID- 29455287
TI  - Ionic liquid phases with comprehensive two-dimensional gas chromatography of
      fatty acid methyl esters.
AB  - New generation inert ionic liquid (iIL) GC columns IL60i, IL76i and IL111i,
      comprising phosphonium or imidazolium cationic species, were investigated for
      separation of fatty acid methyl esters (FAME). In general, the iIL phases provide
      comparable retention times to their corresponding conventional columns, with only
      minor selectivity differences. The average tailing factors and peak widths were
      noticeably improved (reduced) for IL60i and IL76i, while they were slightly
      improved for IL111i. Inert IL phase columns were coupled with conventional IL
      columns in comprehensive two-dimensional GC (GC * GC) with a solid-state
      modulator which offers variable modulation temperature (TM), programmable TM
      during analysis and trapping stationary phase material during the trap/release
      (modulation) process, independent of oven T and column sets. Although IL phases
      are classified as polar, relative polarity of the two phases comprising
      individual GC * GC column sets permits combination of less-polar IL/polar IL and
      polar IL/less-polar IL column sets; it was observed that a polar/less-polar
      column set provided better separation of FAME. A higher first dimension (1D)
      phase polarity combined with a lower 2D phase polarity, for instance 1D IL111i
      with 2D IL59 gave the best result; the greater difference in 1D/2D phase polarity
      results in increasing occupancy of peak area in the 2D space. The IL111i/IL59
      column set was selected for analysis of fatty acids in fat and oil products
      (butter, margarine, fish oil and canola oil). Compared with the conventional
      IL111, IL111i showed reduced column bleed which makes this more suited to GC * GC
      analysis of FAME. The proposed method offers a fast profiling approach with good
      repeatability of analysis of FAME.

PMID- 29455289
TI  - Fluoride Alters Serum Elemental (Calcium, Magnesium, Copper, and Zinc)
      Homeostasis Along with Erythrocyte Carbonic Anhydrase Activity in Fluorosis
      Endemic Villages and Restores on Supply of Safe Drinking Water in School-Going
      Children of Nalgonda District, India.
AB  - The present study aimed to determine the serum trace elements (copper (Cu), zinc
      (Zn), calcium (Ca), magnesium (Mg)) along with erythrocyte carbonic anhydrase
      (CA) activity and effect of intervention with safe drinking water for 5 years in
      the school children of fluorosis endemic area. For this purpose, three categories
      of villages were selected based on drinking water fluoride (F): Category I
      (control, F = 1.68 mg/L), category II (affected F = 3.77 mg/L), and category III
      (intervention village) where initial drinking water F was 4.51 mg/L, and since
      the last 5 years, they were drinking water containing < 1.0 mg/L F. The results
      revealed that urinary F was significantly (P < 0.05) higher in category II
      compared to categories I and III. A significant (P < 0.05) increase in serum Cu
      and Mg was observed in category II compared to category I. Serum Zn and Ca was
      significantly (P < 0.05) decreased in categories II and III compared to category
      I. The erythrocyte CA activity was decreased in the category II compared to
      category I. However, in the category III, erythrocyte CA activity was comparable
      to the control group. In conclusion, F exposure altered elemental homeostasis
      which has restored to some extent on intervention by safe drinking water for 5
      years in school-going children.

PMID- 29455288
TI  - Mycophenolate Mofetil Protects Septic Mice via the Dual Inhibition of
      Inflammatory Cytokines and PD-1.
AB  - Due to the imbalance between hyper-inflammation and hypo-inflammation, which are
      characterized by excessive cytokine productions and programmed death 1 (PD-1)
      upregulation, respectively, sepsis remains a highly lethal inflammatory syndrome
      with limited effective therapies. Mycophenolate mofetil (MMF), an
      immunosuppressant, has been reported to attenuate various inflammatory diseases.
      However, the role of MMF in sepsis therapy remains to be elucidated. C57BL-6J
      mice underwent cecal ligation and puncture (CLP) and were treated either with or
      without MMF. Survival rate and organ injuries were compared. Cytokine levels,
      bacteria clearance, apoptosis of spleen and peritoneal macrophages, and PD-1
      expression were assessed. At the beginning of CLP, 60 mg/kg MMF administered by
      gavage significantly protected septic mice, which was evidenced by improved
      survival and attenuated organ injuries, decreased cytokines, lower bacterial
      loads, and alleviated immune cell apoptosis. In addition, immune cells in the MMF
      mice showed lower PD-1 expression and improved immune response to pathogeny
      stimuli. MMF protects septic mice via the dual inhibition of cytokine releasing
      and PD-1 expression.

PMID- 29455290
TI  - Laparoscopic hemi-splenectomy.
AB  - Laparoscopic splenectomy is now established as a safe and feasible procedure.
      However, it remains associated with some short- and long-term postoperative
      complications, especially infectious complications. To our knowledge, this is the
      first report (with video) focusing on the safety and feasibility of laparoscopic
      hemi-splenectomy and its surgical outcomes for the treatment of splenic abscesses
      causing septic emboli. This technique combines the immunological benefits of
      partial splenectomy and the postoperative benefits of a minimally invasive
      approach. Further studies are needed to standardize this technique and to assess
      its immunological and surgical benefits.

PMID- 29455291
TI  - The role of 'jackpot' stimuli in maladaptive decision-making: dissociable effects
      of D1/D2 receptor agonists and antagonists.
AB  - RATIONALE: Laboratory experiments often model risk through a choice between a
      large, uncertain (LU) reward against a small, certain (SC) reward as an index of
      an individual's risk tolerance. An important factor generally lacking from these
      procedures are reward-associated cues that may modulate risk preferences.
      OBJECTIVE: We tested whether the addition of cues signaling 'jackpot' wins to LU
      choices would modulate risk preferences and if these cue effects were mediated by
      dopaminergic signaling. METHODS: Three groups of rats chose between LU and SC
      rewards for which the LU probability of reward decreased across blocks. The
      unsignaled group received a non-informative stimulus of trial outcome. The
      signaled group received a jackpot signal prior to reward delivery and blackout on
      losses. The signaled-light group received a similar jackpot for wins, but a
      salient loss signal distinct from the win signal. RESULTS: Presenting win signals
      decreased the discounting of LU value for both signaled groups regardless of loss
      signal, while the unsignaled group showed discounting similar to previous
      research without cues. Pharmacological challenges with D1/D2 agonists and
      antagonists revealed that D1 antagonism increased and decreased sensitives to the
      relative probability of reward for unsignaled and signaled groups, respectively,
      while D2 agonists decreased sensitivities to the relative magnitude of reward.
      CONCLUSION: The results highlight how signals predictive of wins can promote
      maladaptive risk taking in individuals, while loss signals have reduced effect.
      Additionally, the presence of reward-predictive cues may change the underlying
      neurobehavioral mechanisms mediating decision-making under risk.

PMID- 29455293
TI  - Variations of transverse foramina in cervical vertebrae: what happens to the
      vertebral artery?
AB  - PURPOSE: The purpose of this study is to examine variations of the foramen
      transversarium and the vertebral artery in computed tomography angiographies
      (CTa) of the cervical spine, investigate their coexistence, and present possible
      considerations regarding such variations in spine surgical procedures. METHODS:
      Fifty CTa of the neck were retrospectively reviewed. Transverse and
      anteroposterior diameter of the foramen and diameter of the vertebral artery were
      measured. Variations of the foramen and the vertebral artery were detected.
      RESULTS: Cervical CTa of 32 males and 18 females (mean age 66.4 +/- 10.78 years),
      all belonging to the Indo-European race, were reviewed. Variations of the foramen
      transversarium were found in 17 vertebrae (4.85%) of 15 patients (30%).
      Duplication of the foramen was the most frequent variation, followed by the open
      foramen, the absence of the foramen, the triple foramen, and the hypoplastic
      foramen. Variations of the vertebral artery were found in 7 patients (14%) and
      asymmetry was found in 12 (24%) patients. Moreover, six patients presented with
      hypoplastic vertebral arteries (12%). When examining coexistence, 60% of patients
      exhibiting variations in the transverse foramen were also exhibiting variations
      or asymmetry in the vertebral artery, compared to 25.7% of patients with no
      foramen variations (p = 0.02). CONCLUSIONS: Vertebral artery injury is not common
      but may be a disastrous complication during cervical spine surgery. Proper
      preoperative planning is essential for any surgeon and exact knowledge of the
      anatomy in each patient is essential. This study strongly recommends the
      preoperative use of a CTa when suspicion of a variation is present and implied by
      a foramen variation. These slides can be retrieved under Electronic Supplementary
      Material.

PMID- 29455292
TI  - Effects of the nicotinic agonist varenicline, nicotinic antagonist r-bPiDI, and
      DAT inhibitor (R)-modafinil on co-use of ethanol and nicotine in female P rats.
AB  - RATIONALE: Co-users of alcohol and nicotine are the largest group of
      polysubstance users worldwide. Commonalities in mechanisms of action for ethanol
      (EtOH) and nicotine proposes the possibility of developing a single
      pharmacotherapeutic to treat co-use. OBJECTIVES: Toward developing a preclinical
      model of co-use, female alcohol-preferring (P) rats were trained for voluntary
      EtOH drinking and i.v. nicotine self-administration in three phases: (1) EtOH
      alone (0 vs. 15%, two-bottle choice), (2) nicotine alone (0.03 mg/kg/infusion,
      active vs. inactive lever), and (3) concurrent access to both EtOH and nicotine.
      Using this model, we examined the effects of (1) varenicline, a nicotinic
      acetylcholine receptor (nAChR) partial agonist with high affinity for the
      alpha4beta2* subtype; (2) r-bPiDI, a subtype-selective antagonist at alpha6beta2*
      nAChRs; and (3) (R)-modafinil, an atypical inhibitor of the dopamine transporter
      (DAT). RESULTS: In phases 1 and 2, pharmacologically relevant intake of EtOH and
      nicotine was achieved. In the concurrent access phase (phase 3), EtOH consumption
      decreased while nicotine intake increased relative to phases 1 and 2. For drug
      pretreatments, in the EtOH access phase (phase 1), (R)-modafinil (100 mg/kg)
      decreased EtOH consumption, with no effect on water consumption. In the
      concurrent access phase, varenicline (3 mg/kg), r-bPiDI (20 mg/kg), and (R)
      modafinil (100 mg/kg) decreased nicotine self-administration but did not alter
      EtOH consumption, water consumption, or inactive lever pressing. CONCLUSIONS:
      These results indicate that therapeutics which may be useful for smoking
      cessation via selective inhibition of alpha4beta2* or alpha6beta2* nAChRs, or DAT
      inhibition, may not be sufficient to treat EtOH and nicotine co-use.

PMID- 29455294
TI  - Cervicothoracic spine duplication: a 10-year follow up of a neurological intact
      boy.
AB  - PURPOSE: Spine duplication is a very rare condition with the literature being
      composed of only case reports. All previously reported cases were thoracolumbar
      spine duplications. Here, we report cervicothoracic spine duplication in a
      neurological intact male. According to our knowledge, it is the first case in the
      literature of cervicothoracic spine duplication. CLINICAL PRESENTATION: A 3-year
      old patient presented to a primary physician with a complaint of short stature.
      He was referred to our department with suspected spinal deformity. Computerized
      tomography imaging revealed anterior bony structure duplication and posterior
      dysmorphic elements at the C5-T9 levels. Magnetic resonance imaging revealed a
      syrinx cavity which splits cord at the duplication level and the relation of the
      syrinx with posterior mediastinum through anterior bone defect. He was followed
      up for 10 years. CONCLUSION: In the literature, spine duplication has been
      classified as a severe form of split cord malformation because of the concurrence
      of bone duplication with split spinal cord malformation (SCM). This case presents
      a distinct form of SCM which shows non-duplicated dural tube as unclassified and
      cervicothoracic duplication level without neurological deficitis. Treatment of
      SCM was based on removal of splitting fibrous/osseous process. Neurologic intact
      spine duplication could be followed up without surgical intervention.

PMID- 29455295
TI  - Is extreme climate or moderate climate more conducive to longevity in China?
AB  - Climate is closely related to human longevity. In China, there are many climate
      types. According to national population censuses from 1982 to 2000, most
      provinces with a high ratio of centenarians are located in western and
      northwestern China far from the sea; these areas are characterized by a dry, cold
      climate, very high altitude, very high daily temperature range, strong winds, and
      partial hypoxia. Meanwhile, provinces with a high ratio of nonagenarians from
      1982 to 2000 are located in southern China near the sea. Previous studies have
      attributed the high ratio of centenarians in western and northwestern China to
      the extreme local climate. However, centenarians in these areas decreased greatly
      in 2010, whereas residents in southern China frequently reached 90 to 100 years
      old in 2010. This study aims to explain this strange phenomenon and find whether
      extreme climate in Tibetan plateau and northwestern China or moderate climate in
      southern China is more conducive to longevity. The study found that mortality
      rate in Tibetan plateau is much higher than southern China, then a population
      evolution experiment was proposed to compare longevity indicators between low
      mortality rate and high mortality rate and shows that longevity indicators will
      decrease in the near future and increase above their original levels after
      several decades when the mortality rate is decreased. Results of this study show
      individuals in northwestern China do not live as long as those in eastern and
      southern China. A moderate climate is more conducive to longevity than extreme
      climate in China. The longevity of a region should be judged by long-term
      longevity indicators.

PMID- 29455296
TI  - Effects of balneotherapy and spa therapy on levels of cortisol as a stress
      biomarker: a systematic review.
AB  - Balneotherapy and spa therapy are well-known practices, even though limited
      evidence has been produced about their biological effects. This systematic review
      primarily aims at assessing if balneotherapy, mud/peloid therapy, and spa therapy
      may influence cortisol levels. Secondarily, it aims at understanding if these
      interventions may improve stress resilience. PubMed/Medline, Embase, and Cochrane
      Library were searched for relevant articles in English or Italian about studies
      involving healthy and sub-healthy subjects or patients with a diagnosed disease
      about effects of balneotherapy, mud/peloid therapy, and spa therapy on serum and
      salivary cortisol levels. Fifteen studies involving 684 subjects were included.
      Five studies investigated biological effects of balneotherapy alone. Two of them
      reported significant changes of cortisol levels in healthy participants. The
      other three studies reported no significant variations in patients with rheumatic
      conditions. No studies investigated biological effects of mud/peloid therapy
      alone. Ten studies investigated biological effects of spa therapy with or without
      included mud/peloid therapy, and in all but two studies, significant variations
      of cortisol levels were reported. Our main findings suggest that balneotherapy
      may have the potential to influence cortisol levels in healthy subjects, in such
      a way as to improve stress resilience. Spa therapy with or without included
      mud/peloid therapy demonstrated the same potential to influence cortisol levels
      also in sub-healthy subjects and in patients with a diagnosed disease. Therefore,
      balneotherapy and spa therapy may be considered as useful interventions for the
      management of stress conditions. Further investigation is needed because of
      limited available data.

PMID- 29455297
TI  - Pan European Phenological database (PEP725): a single point of access for
      European data.
AB  - The Pan European Phenology (PEP) project is a European infrastructure to promote
      and facilitate phenological research, education, and environmental monitoring.
      The main objective is to maintain and develop a Pan European Phenological
      database (PEP725) with an open, unrestricted data access for science and
      education. PEP725 is the successor of the database developed through the COST
      action 725 "Establishing a European phenological data platform for climatological
      applications" working as a single access point for European-wide plant
      phenological data. So far, 32 European meteorological services and project
      partners from across Europe have joined and supplied data collected by volunteers
      from 1868 to the present for the PEP725 database. Most of the partners actively
      provide data on a regular basis. The database presently holds almost 12 million
      records, about 46 growing stages and 265 plant species (including cultivars), and
      can be accessed via http://www.pep725.eu/ . Users of the PEP725 database have
      studied a diversity of topics ranging from climate change impact, plant
      physiological question, phenological modeling, and remote sensing of vegetation
      to ecosystem productivity.

PMID- 29455299
TI  - Prostate-specific membrane antigen in breast cancer: a comprehensive evaluation
      of expression and a case report of radionuclide therapy.
AB  - PURPOSE: Prostate-specific membrane antigen (PSMA), a protein product of the
      folate hydrolase 1 (FOLH1) gene, is gaining increasing acceptance as a target for
      positron emission tomography/computer tomography (PET/CT) imaging in patients
      with several cancer types, including breast cancer. So far, PSMA expression in
      breast cancer endothelia has not been sufficiently characterized. METHODS: This
      study comprised 315 cases of invasive carcinoma of no special type (NST) and
      lobular breast cancer (median follow-up time 9.0 years). PSMA expression on tumor
      endothelia was detected by immunohistochemistry. Further, vascular mRNA
      expression of the FOLH1 gene (PSMA) was investigated in a cohort of patients with
      invasive breast cancer provided by The Cancer Genome Atlas (TCGA). RESULTS: Sixty
      percent of breast cancer cases exhibited PSMA-positive endothelia with higher
      expression rates in tumors of higher grade, NST subtype with Her2-positivity, and
      lack of hormone receptors. These findings were confirmed on mRNA expression
      levels. The highest PSMA rates were observed in triple-negative carcinomas (4.5 *
      higher than in other tumors). Further, a case of a patient with metastatic breast
      cancer showing PSMA expression in PET/CT imaging and undergoing PSMA radionuclide
      therapy is discussed in detail. CONCLUSIONS: This study provides a rationale for
      the further development of PSMA-targeted imaging in breast cancer, especially in
      triple-negative tumors.

PMID- 29455298
TI  - Patient-reported predictors of early treatment discontinuation: treatment-related
      symptoms and health-related quality of life among postmenopausal women with
      primary breast cancer randomized to anastrozole or exemestane on NCIC Clinical
      Trials Group (CCTG) MA.27 (E1Z03).
AB  - PURPOSE: Aromatase inhibitors are the most commonly prescribed adjuvant endocrine
      therapy for hormone-dependent early breast cancer in postmenopausal women. Among
      Canadian Cancer Trials Group MA.27 participants, anastrozole and exemestane had
      comparable 5-year event-free survival. This companion study examined differences
      in patient-reported treatment-related symptoms (TRS) and health-related quality
      of life (HRQL) among postmenopausal women randomized to anastrozole or
      exemestane. METHODS: MA.27 participants (N = 686, of 7576) randomized to 5 years
      of anastrozole (1 mg/day, n = 371, Arm A) or exemestane (25 mg/day, n = 315, Arm
      E) completed the 56-item Functional Assessment of Cancer Therapy-Endocrine
      Symptoms (FACT-ES) questionnaire to assess TRS and HRQL. The FACT-ES was
      completed at baseline, 3, 6, 12, and 24 months. RESULTS: No significant
      differences in FACT-ES median scores measuring TRS and HRQL were observed between
      treatment arms at any time point. Change in TRS from baseline was statistically
      significant at 3, 6, 12, and 24 months. HRQL was stable over time in both arms.
      Greater TRS burden was associated with poorer HRQL (coefficient = 0.57, p <
      0.001). Twenty percent of patients discontinued AI therapy by month 24 and 32%
      discontinued AIs at 4 years. In both arms, patients reporting more side effect
      bother prior to initiating study treatment had a higher risk of discontinuing
      treatment before completing protocol therapy (hazard ratio [HR] 1.29, 95% CI 1.08
      1.55, p = 0.01). CONCLUSIONS: TRS and HRQL were comparable between anastrozole
      and exemestane. TRS negatively affect HRQL. Women who report being bothered by
      treatment side effects prior to initiating an AI are at increased risk for early
      treatment discontinuation.

PMID- 29455300
TI  - Patterns of oral and dental care education and utilization in head and neck
      cancer patients.
AB  - PURPOSE: The purpose of this study was to examine patterns of oral health care
      among patients undergoing oral cancer therapy in order to better understand how
      oral care is being utilized, what types of providers are being utilized at
      various stages of cancer therapy, and assessing patients' satisfaction with the
      care they received at these stages. METHODS: An online survey was conducted via
      the Oral Cancer Foundation's support group message board. Participants were asked
      about their oral care immediately prior to cancer therapy, during cancer therapy,
      and post cancer therapy. The participants were also given the opportunity to
      provide open response feedback on their oral care which was analyzed
      qualitatively. RESULTS: Seventy-four participants completed the survey.
      Participants reported being informed that they needed to receive an oral
      evaluation 72.6 and 53.6% of the time in the pre- and post-treatment stages,
      respectively. Compliance with this recommendation was 71.2% pre cancer therapy
      but dropped precipitously to 49.2% post cancer therapy. Pre- and post-therapy
      oral care was provided most commonly by the patient's usual dentist 41.1 and
      55.9%, respectively, with medical providers predominating the treatment phase,
      77.7%. Patients reported dissatisfaction rates of 29.0, 20.6, and 21.0%
      sequentially. CONCLUSIONS: There is a general lack of consistency with how, when,
      and from whom oral cancer patients receive their oral health education. It is
      likely that this contributes to insufficient education resulting in high levels
      of patient dissatisfaction with their oral care.

PMID- 29455301
TI  - Sexual functioning among early post-treatment breast cancer survivors.
AB  - PURPOSE: This study aims (1) to estimate percentages of partnered women who are
      sexually active over the first 2 years post-breast cancer diagnosis; (2) to
      identify factors related to sexual inactivity; and (3) to evaluate separately,
      among both sexually active and inactive survivors, the relation between sexual
      problems and treatment-related variables, symptoms, and psychosocial factors.
      METHODS: Longitudinal observational study of breast cancer survivors recruited
      within 8 months of cancer diagnosis and followed for 18 months. The main outcome
      measures were (1) being sexually active/inactive in the past month and (2) sexual
      problems assessed with the four-item sexual problem domain of the Quality of Life
      in Adult Cancer Survivors (QLACS) scale. RESULTS: At baseline, 52.4% of women
      reported being sexually active in the past month. This percentage increased to
      60.7% 18 months later. In multivariable repeated-measures analyses, age, past
      chemotherapy, depressive symptoms, and lower perceived attractiveness were
      related to inactivity. Sexually inactive women reported more problems on the
      QLACS than sexually active women. In stratified multivariable analyses,
      depressive symptoms were related to greater sexual problems for both sexually
      active and inactive women, as was vaginal dryness. Among the sexually active
      women, younger age at diagnosis, less illness intrusiveness, and lower perceived
      attractiveness were related to more problems. CONCLUSIONS: Research has shown
      that sexual functioning/sexual health are key aspects of quality of life for many
      cancer survivors, and are often not addressed by health care providers. Future
      studies should examine how such topics are handled by clinicians in their
      interactions with survivors.

PMID- 29455302
TI  - Patient experiences of a physiotherapy-led multidisciplinary rehabilitative
      intervention after successful treatment for oesophago-gastric cancer.
AB  - PURPOSE: To qualitatively explore the perceived impact of a 12-week
      rehabilitative intervention for oesophago-gastric cancer survivors on their
      physical, mental and social wellbeing. METHODS: Of the 21 participants who
      completed the intervention, 19 took part in a semi-structured focus group
      interview. Four audio-taped focus groups were held, ranging in size from two to
      eight participants. Focus groups were transcribed and analysed using a
      descriptive qualitative approach. RESULTS: At recruitment, participants were 23.5
      +/- 15.2 months post-surgery and all had suboptimal fitness levels. Participants
      reported improvements in their physical capacity and ability to carry out
      activities of daily living during the intervention. These improvements led to
      increased confidence and social connectivity. Other participants were a valuable
      source of information and reassurance, while support from family members was
      variable. Future interventions should educate participants on how to maintain
      gains achieved during the intervention. CONCLUSIONS: Participating in an exercise
      based multidisciplinary rehabilitative intervention reduces isolation and helps
      oesophago-gastric cancer survivors to safely negotiate their physical, emotional
      and social needs as they move further down the path of recovery.

PMID- 29455304
TI  - Correction to: Characterization of bone morphology in CCN5/WISP2 knockout mice.
AB  - In the original publication's title CCN5/WISP5 should have been CCN5/WISP2.

PMID- 29455303
TI  - Extracellular matrix regulation of fibroblast function: redefining our
      perspective on skin aging.
AB  - The dermal extracellular matrix (ECM) comprises the bulk of skin and confers
      strength and resiliency. In young skin, fibroblasts produce and adhere to the
      dermal ECM, which is composed primarily of type I collagen fibrils. Adherence
      allows fibroblasts to spread and exert mechanical force on the surrounding ECM.
      In this state, fibroblasts display a "youthful" phenotype characterized by
      maintenance of the composition and structural organization of the dermal ECM.
      During aging, fibroblast-ECM interactions become disrupted due to fragmentation
      of collagen fibrils. This disruption causes loss of fibroblast spreading and
      mechanical force, which inextricably lead to an "aged" phenotype; fibroblasts
      synthesize less ECM proteins and more matrix-degrading metalloproteinases. This
      imbalance of ECM homeostasis further drives collagen fibril fragmentation in a
      self-perpetuating cycle. This article summarizes age-related changes in the
      dermal ECM and the mechanisms by which these changes alter the interplay between
      fibroblasts and their extracellular matrix microenvironment that drive the aging
      process in human skin.

PMID- 29455305
TI  - Photobiomodulation (PBM) therapy at 904 nm mitigates effects of exercise-induced
      skeletal muscle fatigue in young women.
AB  - Muscle fatigue is a process influenced by several mechanisms such as
      concentration of metabolic substrates, changes in blood flow, and increases in
      reactive oxygen species that impair contractile muscle function. In this context,
      photobiomodulation has been investigated for preventing muscle fatigue, with
      reports of positive effects on muscle performance. This study aimed to
      investigate the effects of 904-nm LASER photobiomodulation on rectus femoris
      muscle performance in young women. Eighteen young women participated in a
      randomized, participant and assessor-blinded crossover trial with placebo
      control. Active LASER (904 nm, 60 mW, 250 Hz, 3.6 J per diode, total dose of
      129.6 J) intervention was applied prior to an isokinetic fatigue protocol
      consisting of a set of 60 concentric quadricep contractions at a constant
      dynamometer angular velocity of 180 degrees /s. Compared to placebo, LASER
      photobiomodulation significantly reduced muscle fatigue across a range of
      indicators including reduced ratings of perceived exertion (P = 0.0139), and
      increased electromyographic fatigue index (EFI) (P = 0.005). The isokinetic
      dynamometer performance analysis demonstrated that LASER photobiomodulation
      increased peak torque (P = 0.04), time to peak torque (P = 0.042), total work (P
      = 0.032), average power (P = 0.0007), and average peak torque (P = 0.019) between
      both experimental conditions. No significant difference was observed for work
      fatigue index (P = 0.29) or for lactate concentration (P > 0.05).
      Photobiomodulation at 904 nm was effective in reducing fatigue levels and
      increasing muscle performance in young active women but had no effect on lactate
      levels.

PMID- 29455307
TI  - Adansonia digitata and Adansonia gregorii fruit shells serve as a protection
      against high temperatures experienced during wildfires.
AB  - The thick and woody shell of the fruit of Adansonia species cannot be explained
      solely by adaptation to zoochory or hydrochory. Since the trunks of Adansonia
      possess a thick and fire-resistant bark and wildfires occur regularly in its
      habitat (savannah), we examined with the African Adanonia digitata and the
      Australian Adansonia gregorii whether the fruit offers protection against high
      heat typically experienced in wildfires. Heat-resistance tests were conducted by
      applying a simple heat test based on known temperature and temperature residence
      times occurring in savannah fires and complemented by tests to reveal the impact
      of heat on germination since long-term seed dormancy is known for Adansonia.
      Germination tests with acid treated and heat treated seeds were performed to
      establish if heat also increased germination rate as effectively as acid
      treatments have been found to do. Heat was found to increase germination rate,
      but not as effectively as treatment with acid, therefore fruits exposed to high
      temperatures experienced in wildfires may have a better chance of germination
      than fruits that were not exposed to wildfires. The ability of the investigated
      fruits to protect seeds from high temperatures suggests that wildfires may have
      played a role in the evolution of the hard-shell structure typically found in
      Adansonia.

PMID- 29455306
TI  - Dentinal tubule sealing effects of 532-nm diode-pumped solid-state laser, gallic
      acid/Fe3+ complex, and three commercial dentin desensitizers.
AB  - The purpose of this study was to compare dentinal tubule sealing effects of a 532
      nm diode-pumped solid-state (DPSS) laser, gallic acid/Fe3+ complex, and three
      commercially available dentin desensitizers. Human premolars (n = 44) extracted
      for orthodontics had standardized cervical cavities prepared, etched (37%
      phosphoric acid) and randomly assigned to either a control (n = 4), or one of
      five treatment groups (n = 8/group). Desensitizing treatments were either a 532
      nm DPSS laser, gallic acid/Fe3+ complex, oxalate-based Super SealTM (SS), DIOTM
      Enamel Coating Pen Pro Tooth (Dio), or adhesive-type Hybrid CoatTM (HC). Dentinal
      fluid flow (DFF) was monitored continuously in real time during the application
      of each desensitizing agent, by using a nanoliter-scaled fluid flow-measuring
      device. Following treatment, morphological changes on dentinal surfaces and
      within tubules were observed by scanning electron microscopy (SEM). DFF rates
      were significantly reduced after treatment in all experimental groups (P < 0.05),
      except SS (P > 0.05). The gallic acid/Fe3+ complex reduced DFF rates the most,
      and significantly (P < 0.05) more than the three commercial dentin desensitizers.
      There were no significant differences in DFF reduction rates between the gallic
      acid/Fe3+ complex and the DPSS laser groups (P > 0.05). There were no significant
      differences in DFF reduction rates among the three commercial dentin
      desensitizers (P > 0.05). SEM examination of treated dentin showed that the
      degree of occlusion of dentinal tubules correlated closely with the corresponding
      reduction in DFF rates. The gallic acid/Fe3+ complex and 532-nm DPSS laser were
      superior to other desensitizing methods in occluding dentinal tubules and
      reducing DFF rates.

PMID- 29455308
TI  - Fluid therapy and outcome: a prospective observational study in 65 German
      intensive care units between 2010 and 2011.
AB  - BACKGROUND: Outcome data on fluid therapy in critically ill patients from
      randomised controlled trials may be different from data obtained by observational
      studies under "real-life" conditions. We conducted this prospective,
      observational study to investigate current practice of fluid therapy
      (crystalloids and colloids) and associated outcomes in 65 German intensive care
      units (ICUs). In total, 4545 adult patients who underwent intravenous fluid
      therapy were included. The main outcome measures were 90-day mortality, ICU
      mortality and acute kidney injury (AKI). Data were analysed using logistic and
      Cox regression models, as appropriate. RESULTS: In the predominantly post
      operative overall cohort, unadjusted 90-day mortality was 20.1%. Patients who
      also received colloids (54.6%) had a higher median Simplified Acute Physiology
      Score II [25 (interquartile range 11; 41) vs. 17 (7; 31)] and incidence of severe
      sepsis (10.2 vs. 7.4%) on admission compared to patients who received exclusively
      crystalloids (45.4%). 6% hydroxyethyl starch (HES 130/0.4) was the most common
      colloid (57.0%). Crude rates of 90-day mortality were higher for patients who
      received colloids (OR 1.845 [1.560; 2.181]). After adjustment for baseline
      variables, the HR was 1.666 [1.405; 1.976] and further decreased to indicate no
      associated risk (HR 1.003 [0.980; 1.027]) when it was adjusted for vasopressor
      use, severity of disease and transfusions. Similarly, the crude risk of AKI was
      higher in the colloid group (crude OR 3.056 [2.528; 3.694]), after adjustment for
      baseline variables OR 1.941 [1.573; 2.397], and after full adjustment OR 0.696
      [0.629; 0.770]), the risk of AKI turned out to be reduced. The same was true for
      the subgroup of patients treated with 6% HES 130/0.4 (crude OR 1.931 [1.541;
      2.419], adjusted for baseline variables OR 2.260 [1.730; 2.953] and fully
      adjusted OR 0.800 [0.704; 0.910]) as compared to crystalloids only. CONCLUSIONS:
      The present analysis of mostly post-operative patients in routine clinical care
      did not reveal an independent negative effect of colloids (mostly 6% HES 130/0.4)
      on renal function or survival after multivariable adjustment. Signals towards a
      reduced risk in subgroup analyses deserve further study. Trial registration
      ClinicalTrials.gov Identifier: NCT01122277, registered May 11th, 2010.

PMID- 29455309
TI  - Right heart failure caused by direct pressure of distal arch aneurysm.
AB  - We report a rare case of right heart failure caused by distal aortic aneurysm.
      Although aortopulmonary fistula is a common complication of giant aortic arch
      aneurysm, right heart failure caused by mechanical pressure by aneurysm is very
      rare. A 79-year-old female patient presented dyspnea. Contrast computed
      tomography (CT) of the thorax delineated a 78 mm aortic arch aneurysm pressing
      the main to left pulmonary artery and a 40 mm pericardial effusion at maximum
      depth at posterior side. Echocardiography showed the acceleration flow from main
      to left pulmonary artery and moderate pulmonary hypertension. Left ventricular
      function, however, was preserved. We diagnosed right heart failure caused by
      giant aortic arch aneurysm and performed emergency aortic arch aneurysm
      replacement. After the operation, pulmonary artery pressure decreased and right
      heart failure improved.

PMID- 29455310
TI  - Germans learn how to save lives: a nationwide CPR education initiative.
AB  - BACKGROUND: Sudden cardiac death is one of the most frequent causes of death in
      Germany and the third leading cause of death in the industrialized world. Yet,
      the percentage of people providing first aid in the case of sudden cardiac arrest
      in Germany is alarmingly low by international comparison. Training Germans or
      reminding them of the simple but effective steps of resuscitation, so that
      everybody can save a live in an emergency. METHODS: For the campaign
      'Resuscitation Week', physicians and paramedics trained passers-by in
      cardiovascular resuscitation free of charge. Skills were evaluated before and
      after the instruction by means of a questionnaire. RESULTS: Three hundred three
      people aged between 9 and 89 years were trained and evaluated. Forty-nine passers
      by had never participated in a resuscitation course, and 46.8% had participated
      in a course more than 20 years ago. Before the instruction, 41.6% of the passers
      by were confident to be capable of resuscitating a person; after the instruction,
      however, this percentage had risen to 100%! CONCLUSIONS: Saving a life is simple,
      but one has to know what to do in the case of sudden cardiac arrest. The German
      population is being gradually trained in resuscitation using campaigns such as
      'Resuscitation Week' and 'Kids Save Lives' to break down barriers in the long
      term. However, lives are not only saved by training but also by refreshing
      knowledge and skills; thus, a further effective approach may be training all
      holders of a driving license in cardiopulmonary resuscitation in intervals of 5
      years.

PMID- 29455311
TI  - Accelerated molecular breeding of a novel P/TGMS line with broad-spectrum
      resistance to rice blast and bacterial blight in two-line hybrid rice.
AB  - BACKGROUND: Breeding two-line hybrid rice with disease resistance is an effective
      approach to stabilize rice yield in commercial rice production of China. RESULTS:
      We improved the blast and bacterial blight resistance of Guangzhan63-4S, an elite
      photoperiod- and thermo-sensitive male sterile (P/TGMS) line widely used in two
      line hybrid rice, by introducing the R genes Pi2 and Xa7 conferring resistance to
      rice blast and bacterial blight, respectively. Through the backcrossing and gene
      pyramiding breeding coupled with molecular marker-assisted selection, a new
      P/TGMS line Hua1228S carrying Pi2, Xa7, and tms5 was developed. Based on 200,000
      SNP markers by next-generation sequencing, Hua1228S covered 87.6% of the
      recurrent genome, as well as 4.5% of the donor genome from VE6219 and 7.9% from
      YR7029-39. When infected with seven tested Xanthomonas oryzae pv. oryzae strains,
      Hua1228S conferred high resistance (0 level) to six bacterial blight strains.
      Moreover, Hua1228S showed broad-spectrum resistance to rice blast isolates with a
      high resistance frequency of 90.91%. High levels of resistance to leaf blast and
      neck blast were observed under heavy disease pressure in natural field.
      Importantly, Hua1228S showed identical fertility-sterility alteration pattern to
      Guangzhan63-4S. Thus, two hybrid combinations Hua Liangyou 2821 and Hua Liangyou
      284 derived from Hua1228S exhibited enhanced resistance and higher yield compared
      with the control variety Feng Liangyou 4. CONCLUSIONS: These results indicate
      that Hua1228S has tremendous potentiality to increase and stabilize the rice
      yield, through the introgression of two R genes by marker-assisted selection
      strategy.

PMID- 29455312
TI  - Combining baseline TMTV and gene profiling for a better risk stratification in
      diffuse large B cell lymphoma.

PMID- 29455313
TI  - [18F]FDG PET/MR enterography for the assessment of inflammatory activity in
      Crohn's disease: comparison of different MRI and PET parameters.
AB  - PURPOSE: To evaluate the diagnostic performance of integrated whole-body positron
      emission tomography (PET)/magnetic resonance (MR) enterography in patients with
      Crohn's disease (CD). METHODS: Fifty patients with known CD and recurrent
      symptoms underwent ileocolonoscopy (reference standard) as well as PET/MR
      enterography. Seven ileocolonic segments were endoscopically analysed using the
      Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD) and
      additionally classified into three categories of inflammation (none, mild to
      moderate and severe ulcerative inflammation). A total of 14 PET/MR parameters
      were applied for the assessment of inflamed segments. Contingency tables and the
      chi-squared test were used for the analysis of qualitative parameters, and the
      Mann-Whitney U test and receiver operating characteristic (ROC) curve for the
      analysis of quantitative parameters. The PET/MR parameters were ranked according
      to their diagnostic value by random forest classification. Correlations between
      PET/MR parameters and the severity of inflammation on endoscopy and SES-CD were
      tested using Spearman's rank correlation test. RESULTS: A total of 309 segments
      could be analysed. Based on multivariate regression analysis, wall thickness and
      the comb sign were the most important parameters for predicting segments with
      active inflammation of any type. SUVmax ratio of the bowel segment (relative to
      SUVmax of the liver) was the most important parameter for detecting segments with
      severe ulcerative inflammation. Wall thickness was the only parameter that
      moderately correlated with inflammation severity on endoscopy as well as with SES
      CD (rho = 0.56 and 0.589, both p < 0.001). CONCLUSION: PET/MR enterography is an
      excellent noninvasive diagnostic method, and both MR parameters and PET findings
      provided high accuracy in detecting inflamed segments.

PMID- 29455314
TI  - Young Adults Changing Insurance Status: Gaps in Health Insurance Literacy.

PMID- 29455315
TI  - Mitogenomes of two neotropical bird species and the multiple independent origin
      of mitochondrial gene orders in Passeriformes.
AB  - At least four mitogenome arrangements occur in Passeriformes and differences
      among them are derived from an initial tandem duplication involving a segment
      containing the control region (CR), followed by loss or reduction of some parts
      of this segment. However, it is still unclear how often duplication events have
      occurred in this bird order. In this study, the mitogenomes from two species of
      Neotropical passerines (Sicalis olivascens and Lepidocolaptes angustirostris)
      with different gene arrangements were first determined. We also estimated how
      often duplication events occurred in Passeriformes and if the two CR copies
      demonstrate a pattern of concerted evolution in Sylvioidea. One tissue sample for
      each species was used to obtain the mitogenomes as a byproduct using next
      generation sequencing. The evolutionary history of mitogenome rearrangements was
      reconstructed mapping these characters onto a mitogenome Bayesian phylogenetic
      tree of Passeriformes. Finally, we performed a Bayesian analysis for both CRs
      from some Sylvioidea species in order to evaluate the evolutionary process
      involving these two copies. Both mitogenomes described comprise 2 rRNAs, 22
      tRNAs, 13 protein-codon genes and the CR. However, S. olivascens has 16,768 bp
      showing the ancestral avian arrangement, while L. angustirostris has 16,973 bp
      and the remnant CR2 arrangement. Both species showed the expected gene order
      compared to their closest relatives. The ancestral state reconstruction
      suggesting at least six independent duplication events followed by partial
      deletions or loss of one copy in some lineages. Our results also provide evidence
      that both CRs in some Sylvioidea species seem to be maintained in an apparently
      functional state, perhaps by concerted evolution, and that this mechanism may be
      important for the evolution of the bird mitogenome.

PMID- 29455317
TI  - Genetic zygosity of mature ovarian teratomas, struma ovarii, and ovarian
      carcinoids.
AB  - Although ovarian monodermal teratomas, including struma ovarii and carcinoids,
      are closely associated with mature teratomas, their genetic basis is poorly
      understood. A series of mature and monodermal ovarian teratomas were analyzed by
      short tandem repeat genotyping to evaluate their genetic zygosity and its
      associations. Informative DNA genotyping data were obtained for ten mature
      teratomas, six struma ovarii, and three carcinoids (one insular, one trabecular,
      and one mucinous). A homozygous genotype was present in five of the ten (50%)
      mature teratomas, three of the six (50%) struma ovarii, and one of the three
      (33%) ovarian carcinoids. There was no significant difference in genetic zygosity
      between mature and monodermal teratomas. Patients' age was not correlated with
      the genetic zygosity: the youngest age in the homozygous tumor group of patients
      was 4 years. It is suggested that an oocyte after meiosis I, which has escaped
      from meiotic arrest, is a significant cause of these tumors. Although one mature
      teratoma was a rare case with lactating adenoma-like breast tissue, its genetic
      zygosity was concordant with that of the surrounding teratomatous tissue. In one
      ovarian carcinoid, the carcinoid and accompanying teratomatous components showed
      matching zygosity at all but one locus: the carcinoid was heterozygous but
      teratoma was homozygous at one pericentromeric locus. This suggests that not all
      carcinoids are secondary neoplasms arising from a fully developed mature
      teratoma: some are neoplasms deviating from a developing mature teratoma.

PMID- 29455316
TI  - Investigation of major genetic alterations in neuroblastoma.
AB  - Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. This
      malignancy shows a wide spectrum of clinical outcome and its prognosis is
      conditioned by manifold biological and genetic factors. We investigated the tumor
      genetic profile and clinical data of 29 patients with NB by multiplex ligation
      dependent probe amplification (MLPA) to assess therapeutic risk. In 18 of these
      tumors, MYCN status was assessed by fluorescence in situ hybridization (FISH).
      Copy number variation was also determined for confirming MLPA findings in two 6p
      loci. We found 2p, 7q and 17q gains, and 1p and 11q losses as the most frequent
      chromosome alterations in this cohort. FISH confirmed all cases of MYCN
      amplification detected by MLPA. In view of unexpected 6p imbalance, copy number
      variation of two 6p loci was assessed for validating MLPA findings. Based on
      clinical data and genetic profiles, patients were stratified in pretreatment risk
      groups according to international consensus. MLPA proved to be effective for
      detecting multiple genetic alterations in all chromosome regions as requested by
      the International Neuroblastoma Risk Group (INRG) for therapeutic stratification.
      Moreover, this technique proved to be cost effective, reliable, only requiring
      standard PCR equipment, and attractive for routine analysis. However, the
      observed 6p imbalances made PKHD1 and DCDC2 inadequate for control loci. This
      must be considered when designing commercial MLPA kits for NB. Finally, four
      patients showed a normal MLPA profile, suggesting that NB might have a more
      complex genetic pattern than the one assessed by presently available MLPA kits.

PMID- 29455318
TI  - Expression of terminal deoxynucleotidyl transferase (TdT) in classical seminoma:
      a potential diagnostic pitfall.
AB  - Seminomas are the most frequent testicular tumors and in spite of specific
      markers some histological subtypes can be diagnostically challenging due to the
      potential overlap of morphologic features and a variant antigen expression.
      Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase present in
      hematogones, thymic T cells, lymphoblastic lymphoma/leukemia (LBL), and in some
      cases of acute myeloid leukemia but so far has not been described to be expressed
      in seminomas. After observing a reactivity of TdT in one case of seminoma, we
      analyzed ten additional tumors by immunohistochemistry to determine their
      spectrum of reactivity for TdT. In all seminoma cases investigated (10/10) as
      well as in two tumor-associated germ cell neoplasias in situ (2/2) the TdT
      staining intensity was variable but was often moderate to strong and restricted
      to the nucleus. We conclude that TdT expression in seminomas could represent a
      diagnostic pitfall in the differential diagnosis of LBL, particularly because
      both may lack CD45 and/or CD20 expression and-concerning relapse in long-term
      survivors of testicular cancer-LBL is the most frequent secondary neoplasm in the
      patients.

PMID- 29455319
TI  - Development and Pilot Testing of a Decision Aid for Genomic Research Participants
      Notified of Clinically Actionable Research Findings for Cancer Risk.
AB  - Germline genomic testing is increasingly used in research to identify genetic
      causes of disease, including cancer. However, there is evidence that individuals
      who are notified of clinically actionable research findings have difficulty
      making informed decisions regarding uptake of genetic counseling for these
      findings. This study aimed to produce and pilot test a decision aid to assist
      participants in genomic research studies who are notified of clinically
      actionable research findings to make informed choices regarding uptake of genetic
      counseling. Development was guided by published literature, the International
      Patient Decision Aid Standards, and the expertise of a steering committee of
      clinicians, researchers, and consumers. Decision aid acceptability was assessed
      by self-report questionnaire. All 19 participants stated that the decision aid
      was easy to read, clearly presented, increased their understanding of the
      implications of taking up research findings, and would be helpful in decision
      making. While low to moderate levels of distress/worry were reported after
      reading the booklet, a majority of participants also reported feeling reassured.
      All participants would recommend the booklet to others considering uptake of
      clinically actionable research findings. Results indicate the decision aid is
      acceptable to the target audience, with potential as a useful decision support
      tool for genomic research participants.

PMID- 29455320
TI  - Elevated serum Krebs von den Lungen-6 in systemic sclerosis: a marker of lung
      fibrosis and severity of the disease.
AB  - OBJECTIVES: We aimed to assess the clinical significance of Krebs von den Lungen
      6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a
      French cohort of patients with systemic sclerosis (SSc). METHODS: Serum KL-6
      concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in
      75 SSc patients. Patients were divided into two groups according to the presence
      of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High
      Resolution Computed Tomography. Pulmonary function tests, main manifestations and
      severity of the lung disease (Medsger's severity scale) were collected. RESULTS:
      KL-6 serum concentrations were significantly higher in SSc-ILD patients than in
      those without ILD (p < 10-4) and were inversely correlated with forced vital
      capacity, total lung capacity and diffuse lung capacity of carbon monoxide. Serum
      KL-6 level superior to 872 U/ml appeared as the optimal cut-off value associated
      with ILD. Patients with a restrictive pulmonary syndrome and dyspnoea had
      significant higher KL-6 serum concentrations. SSc patients with anti
      topoisomerase 1 antibodies had higher KL-6 serum levels than patients with anti
      centromere antibodies (p < 10- 4). ILD and anti-topoisomerase 1 antibodies were
      independent factors associated with KL-6 in multivariate analysis. Interestingly,
      KL-6 serum concentrations positively increased with the patient lung severity.
      CONCLUSIONS: Our study confirms that KL-6 is an accurate biomarker for the
      diagnosis of SSc-ILD in a French cohort of patients. High KL-6 levels should
      prompt physicians to assess ILD with pulmonary imaging and pulmonary functions
      tests. Prospective clinical studies are still required to determine whether
      levels of KL-6 might predict progression of ILD as well as its usefulness in the
      timing of therapeutic intervention.

PMID- 29455321
TI  - Respiratory quotient estimations as additional prognostic tools in early septic
      shock.
AB  - Central venous-to-arterial carbon dioxide difference (PcvaCO2), and its
      correction by the arterial-to-venous oxygen content difference (PcvaCO2/CavO2)
      have been proposed as additional tools to evaluate tissue hypoxia. Since the
      relationship between pressure and content of CO2 (CCO2) might be affected by
      several factors, some authors advocate for the use of CcvaCO2/CavO2. The aim of
      the present study was to explore the factors that might intervene in the
      difference between PcvaCO2/CavO2 and CcvaCO2/CavO2, and to analyze their
      association with mortality. Observational study in a 30-bed mixed ICU. Fifty-two
      septic shock patients within the first 24 h of ICU admission were studied. After
      restoration of mean arterial pressure, hemodynamic and metabolic parameters were
      evaluated. A total of 110 sets of measurements were performed. Simultaneous
      PcvaCO2/CavO2 and CcvaCO2/CavO2 values were correlated, but agreement analysis
      showed a significant proportional bias. The difference between PcvaCO2/CavO2 and
      CcvaCO2/CavO2 was independently associated with pH, ScvO2, baseline CcvaCO2/CavO2
      and hemoglobin. A stepwise regression analysis showed that pH was the single best
      predictor for the magnitude of such difference, with very limited effect of other
      variables. At inclusion, variables associated with ICU-mortality were lactate,
      pH, PcvaCO2/CavO2, and the difference between PcvaCO2/CavO2 and CcvaCO2/CavO2.
      Initial ScvO2, PcvaCO2, CcvaCO2/CavO2, and cardiac index were not different in
      survivors and non-survivors. In a population of early septic shock patients,
      simultaneous values of PcvaCO2/CavO2 and CcvaCO2/CavO2 were not equivalent, and
      the main determinant of the magnitude of the difference between these two
      parameters was pH. The PcvaCO2/CavO2 ratio was associated with ICU mortality,
      whereas CcvaCO2/CavO2 was not.

PMID- 29455322
TI  - A novel device for air removal from vascular access line: a bench study.
AB  - Efficient air removal from a vascular access line is a key step to prevent air
      embolism. Existing devices, especially for rapid infusers, are far from optimum.
      In this study, we developed a novel device, vascular access line air removal
      device (VALARD), and compared its efficiency of air removal and pause time of
      forward bulk flow with a commonly used device, the Belmont pump. Part I
      experiment, saline was infused at a forward bulk flow rate of 250, 500, and 750
      mL/min. Meanwhile, air was introduced into the infusion line at a rate of 5, 10,
      and 15 mL/min for each bulk flow rate. Air bubbles > 10 uL downstream from either
      the VALARD or the Belmont pump and the fraction of pause time of the forward bulk
      flow were determined. Part II experiment, 120 mL of air was rapidly introduced
      into the VALARD at a bulk flow rate of about 500 mL/min. Air bubbles > 10 uL
      downstream from the VALARD, fraction of pause time of the forward bulk flow, and
      the transit time of the 120 mL of air at the working chamber were recorded. The
      VALARD: no air bubbles > 10 uL were detected during any tested combination of air
      injection and bulk flow rates without pause of forward flow. The Belmont pump:
      air bubbles > 10 uL were detected in 60% of the tests with pause of the forward
      flow. The VALARD eliminates air efficiently without pause of the forward bulk
      flow. Further clinical trials are needed to compare the VALARD with other devices
      and to assess its efficiency, safety, and user friendliness.

PMID- 29455324
TI  - Genetic diversity and phylogenetic analysis of Aleutian mink disease virus
      isolates in north-east China.
AB  - Aleutian mink disease is the most important disease in the mink-farming industry
      worldwide. So far, few large-scale molecular epidemiological studies of AMDV,
      based on the NS1 and VP2 genes, have been conducted in China. Here, eight new
      Chinese isolates of AMDV from three provinces in north-east China were analyzed
      to clarify the molecular epidemiology of AMDV. The seroprevalence of AMDV in
      north-east China was 41.8% according to counterimmuno-electrophoresis. Genetic
      variation analysis of the eight isolates showed significant non-synonymous
      substitutions in the NS1 and VP2 genes, especially in the NS1 gene. All eight
      isolates included the caspase-recognition sequence NS1:285 (DQTD?S), but not the
      caspase recognition sequence NS1:227 (INTD?S). The LN1 and LN2 strains had a new
      10-amino-acid deletion in-between amino acids 28-37, while the JL3 strain had a
      one-amino-acid deletion at position 28 in the VP2 protein, compared with the AMDV
      G strain. Phylogenetic analysis based on most of NS1 (1755 bp) and complete VP2
      showed that the AMDV genotypes did not cluster according to their pathogenicity
      or geographic origin. Local and imported ADMV species are all prevalent in mink
      farming populations in the north-east of China. This is the first study to report
      the molecular epidemiology of AMDV in north-east China based on most of NS1 and
      the complete VP2, and further provides information about polyG deletions and new
      variations in the amino acid sequences of NS1 and VP2 proteins. This report is a
      good foundation for further study of AMDV in China.

PMID- 29455323
TI  - Financial Preparation for Retirement in Brazil: a Cross-Cultural Test of the
      Interdisciplinary Financial Planning Model.
AB  - In this investigation, we attempt to replicate the Interdisciplinary Financial
      Planning Model advanced by Hershey et al. (International Journal of Aging and
      Human Development, 70, 1-38, 2010) using a sample of Brazilian adults. This
      model, which was originally tested on individuals from The Netherlands and the
      United States, posits that psychological, social, and economic forces are key
      determinants of retirement planning practices and perceptions of saving adequacy.
      Taken together, fifteen hypotheses were subject to evaluation. Participants were
      167 Brazilian working adults, 21-69 years of age, who were married or
      cohabitating at the time of testing. A path analysis model showed substantial
      support for the theoretical framework, with all variables found to contribute
      directly or indirectly to the prediction of financial planning and saving
      adequacy. Furthermore, two new paths were found to emerge in the Brazilian model
      that were not observed in the original investigation. This cross-national
      replication of the Interdisciplinary Financial Planning Model extends research on
      the topic to a developing country in which relatively few empirical studies of
      retirement planning have been carried out. Other analyses in the article focus on
      direct comparisons between the Brazilian model and the models developed based on
      American and Dutch respondents, with an eye toward better understanding how
      cultural forces shape the retirement planning process. The discussion focuses on
      how models of financial planning, such as the Hershey et al. (2010) model, can
      inform the development of savings-oriented education and intervention programs.

PMID- 29455325
TI  - Development of a luminescence syncytium induction assay (LuSIA) for easily
      detecting and quantitatively measuring bovine leukemia virus infection.
AB  - Bovine leukemia virus (BLV) causes enzootic bovine leukosis and is closely
      related to the human T cell leukemia virus. Since BLV infection mostly occurs via
      cell-to-cell transmission, BLV infectivity is generally measured by culturing BLV
      infected cells with reporter cells that form syncytia upon BLV infection.
      However, this method is time-consuming and requires skill. To visualize the
      infectivity of BLV, we developed a new assay called the luminescence syncytium
      induction assay (LuSIA) that is based on a new reporter cell line designated CC81
      BLU3G. CC81-BLU3G is stably transfected with pBLU3-EGFP, which contains the BLV
      long terminal repeat U3 region linked to the enhanced-green fluorescence protein
      (EGFP) gene. CC81-BLU3G expresses the EGFP in response to BLV Tax expression
      specifically, and forms fluorescing syncytia when transfected with an infectious
      BLV plasmid or when cultured with BLV-infected cells. Compared to the
      conventional assay, LuSIA was more specific and detected cattle samples with low
      proviral loads. The fluorescing syncytia was easily detected by eye and automated
      scanning and LuSIA counts correlated strongly with the proviral load of infected
      cattle (R2 = 0.8942).

PMID- 29455326
TI  - New tetrameric forms of the rotavirus NSP4 with antiparallel helices.
AB  - Rotavirus nonstructural protein 4, the first viral enterotoxin to be identified,
      is a multidomain, multifunctional glycoprotein. Earlier, we reported a Ca2+-bound
      coiled-coil tetrameric structure of the diarrhea-inducing region of NSP4 from the
      rotavirus strains SA11 and I321 and a Ca2+-free pentameric structure from the
      rotavirus strain ST3, all with a parallel arrangement of alpha-helices. pH was
      found to determine the oligomeric state: a basic pH favoured a tetramer, whereas
      an acidic pH favoured a pentamer. Here, we report two novel forms of the coiled
      coil region of NSP4 from the bovine rotavirus strains MF66 and NCDV. These
      crystallized at acidic pH, forming antiparallel coiled-coil tetrameric structures
      without any bound Ca2+ ion. Structural and mutational studies of the coiled-coil
      regions of NSP4 revealed that the nature of the residue at position 131 (Tyr/His)
      plays an important role in the observed structural diversity.

PMID- 29455327
TI  - Cerebral Salt Wasting Complicated by Central Diabetes Insipidus and Growth
      Hormone Deficiency.

PMID- 29455328
TI  - Placental Transfusion in Preterm Neonates.

PMID- 29455329
TI  - Rising Obesity in Children: A Serious Public Health Concern.

PMID- 29455330
TI  - Ocular Manifestations of Pediatric Systemic Diseases.
AB  - Ocular manifestations that occur directly or indirectly as result of a pathologic
      process that involves other parts of the body, in a pediatric population, will be
      discussed here. While a myriad number of systemic conditions have ocular
      manifestations, its importance cannot be undermined because it has implications
      for both diagnosis and treatment. Often, the eye findings can give a clue to the
      systemic diagnosis and at other times, not managing the eye manifestations can
      lead to irreversible blindness although the systemic condition was treated well.
      So, it is important for all clinicians dealing with pediatric population to be
      aware of ocular manifestations of the common systemic conditions. The authors
      discuss the ocular manifestations of the following systemic conditions: Genetic
      and chromosomal anomalies, phakomatoses, metabolic disorders, infectious
      diseases, craniofacial anomalies, muscular disorders, inflammatory disorders and
      miscellaneous.

PMID- 29455332
TI  - Myasthenia Gravis in HIV Positive Girl.

PMID- 29455331
TI  - Newborn Screening Guidelines for Congenital Hypothyroidism in India:
      Recommendations of the Indian Society for Pediatric and Adolescent Endocrinology
      (ISPAE) - Part II: Imaging, Treatment and Follow-up.
AB  - : The Indian Society for Pediatric and Adolescent Endocrinology has formulated
      Clinical Practice Guidelines for newborn screening, diagnosis and management of
      congenital hypothyroidism (CH). This manuscript, part II addresses management and
      follow-up. RECOMMENDATIONS: Screening should be done for every newborn using cord
      blood, or postnatal blood ideally at 48 to 72 h of age. Neonates with screen TSH
      > 20 mIU/L serum units (or >34 mIU/L for samples taken between 24 and 48 h of
      age) should be recalled for confirmation. For screen TSH > 40 mIU/L, immediate
      confirmatory venous T4/FT4 and TSH, and for mildly elevated screen TSH, a second
      screening TSH at 7 to 10 d of age, should be taken. Preterm and low birth weight
      infants should undergo screening at 48-72 h age. Sick babies should be screened
      at least by 7 d of age. Venous confirmatory TSH >20 mIU/L before age 2 wk and >10
      mIU/L after age 2 wk, with low T4 (<10 MUg/dL) or FT4 (<1.17 ng/dL) indicate
      primary CH and treatment initiation. Imaging is recommended by radionuclide
      scintigraphy and ultrasonography after CH is biochemically confirmed but
      treatment should not be delayed till scans are performed. Levothyroxine is
      commenced at 10-15 MUg/kg in the neonatal period. Serum T4/FT4 is measured at 2
      wk and TSH and T4/FT4 at 1 mo, then 2 monthly till 6 mo, 3 monthly from 6 mo-3 y
      and every 3-6 mo thereafter. Babies with the possibility of transient CH should
      be re-evaluated at age 3 y, to assess the need for lifelong therapy.

PMID- 29455334
TI  - Septicemia from Lactobacillus rhamnosus GG, from a Probiotic Enriched Yogurt, in
      a Patient with Autologous Stem Cell Transplantation.
AB  - Probiotic-rich foods are consumed without much restriction. We report here, a
      case of septic shock caused by yogurt derived Lactobacillus species in a 54-year
      old male patient with acute promyelocytic leukemia, in second complete remission,
      and who was an autologous stem cell transplantation recipient. He received high
      dose chemotherapy and autologous peripheral blood stem cell transplantation. He
      ingested commercially available probiotic-enriched yogurt because of severe
      diarrhea. One week later, he developed septic shock, and the pathogen was
      determined by strain-specific PCR analysis as Lactobacillus rhamnosus GG (ATCC
      53103), which was found to be identical with the strain in the yogurt he
      consumed. Thus, because even low virulent Lactobacilli in the probiotic products
      can be pathogenic in the compromised hosts, ingestion of such products should be
      considered with caution in neutropenic patients with severe diarrhea, such as
      stem cell transplantation recipients.

PMID- 29455333
TI  - Stress response factors drive regrowth of quiescent cells.
AB  - Quiescent cells exploit an array of transcription factors to activate stress
      response machinery and maintain survival under nutrient-limited conditions. Our
      recent findings reveal that these transcription factors also play an important
      role in the exit of quiescence and regrowth. By studying Saccharomyces cerevisiae
      under a continuous, nutrient-limited condition, we found that Msn2 and Msn4
      function as master regulators of glycolytic genes in the quiescent-like phase.
      They control the timing of transition from quiescence to growth by regulating the
      accumulation rate of acetyl-CoA, a key metabolite that is downstream of
      glycolysis and drives growth. These findings suggest a model that Msn2/4 not only
      protect the cells from starvation but also facilitate their regrowth from
      quiescence. Thus, understanding the functions of stress response transcription
      factors in metabolic regulation will provide deeper insight into how quiescent
      cells manage the capacity of regrowth.

PMID- 29455335
TI  - Evaluating the Safety and Tolerability of Sacubitril/Valsartan for HFrEF Managed
      Within a Pharmacist Clinic.
AB  - OBJECTIVE: The objective of this research was to describe the use of pharmacist
      managed sacubitril/valsartan therapy in a multi-center, outpatient cardiac group.
      BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor
      (ARNi), is a novel agent for the treatment of heart failure. An ARNi is
      recommended by national guidelines to be used in place of angiotensin-converting
      enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy for
      patients who remain symptomatic. METHODS: A retrospective chart review was
      performed to identify patients initiated and fully titrated on
      sacubitril/valsartan therapy from July 7, 2015 to March 7, 2017. RESULTS: Fifty
      two of the 72 symptomatic heart failure with reduced ejection fraction (HFrEF)
      patients prescribed sacubitril/valsartan during the 21-month period were included
      in this analysis. The average ejection fraction was 26%. The average age was 69
      years. At baseline, 26.9% of patients were not on ACEi/ARB therapy and 13.5% were
      on target-dose therapy. After completing the uptitration process, the maximally
      tolerated dose of sacubitril/valsartan was 5.8% low-dose, 7.7% mid-dose, and
      86.5% target-dose. Loop and thiazide diuretic use decreased significantly. There
      was a significant mean reduction in systolic blood pressure of 6 mmHg with no
      significant changes in serum creatinine, blood urea nitrogen, or potassium
      levels. CONCLUSIONS: With close monitoring and follow-up, ARNi therapy was a safe
      alternative to ACEi/ARB therapy for chronic symptomatic HFrEF when initiated
      within a pharmacist clinic.

PMID- 29455336
TI  - Utilization of organic nitrogen by arbuscular mycorrhizal fungi-is there a
      specific role for protists and ammonia oxidizers?
AB  - Arbuscular mycorrhizal (AM) fungi can significantly contribute to plant nitrogen
      (N) uptake from complex organic sources, most likely in concert with activity of
      soil saprotrophs and other microbes releasing and transforming the N bound in
      organic forms. Here, we tested whether AM fungus (Rhizophagus irregularis)
      extraradical hyphal networks showed any preferences towards certain forms of
      organic N (chitin of fungal or crustacean origin, DNA, clover biomass, or
      albumin) administered in spatially discrete patches, and how the presence of AM
      fungal hyphae affected other microbes. By direct 15N labeling, we also quantified
      the flux of N to the plants (Andropogon gerardii) through the AM fungal hyphae
      from fungal chitin and from clover biomass. The AM fungal hyphae colonized
      patches supplemented with organic N sources significantly more than those
      receiving only mineral nutrients, organic carbon in form of cellulose, or
      nothing. Mycorrhizal plants grew 6.4-fold larger and accumulated, on average,
      20.3-fold more 15N originating from the labeled organic sources than their
      nonmycorrhizal counterparts. Whereas the abundance of microbes (bacteria, fungi,
      or Acanthamoeba sp.) in the different patches was primarily driven by patch
      quality, we noted a consistent suppression of the microbial abundances by the
      presence of AM fungal hyphae. This suppression was particularly strong for
      ammonia oxidizing bacteria. Our results indicate that AM fungi successfully
      competed with the other microbes for free ammonium ions and suggest an important
      role for the notoriously understudied soil protists to play in recycling organic
      N from soil to plants via AM fungal hyphae.

PMID- 29455337
TI  - Arbuscular mycorrhiza facilitates the accumulation of glycyrrhizin and liquiritin
      in Glycyrrhiza uralensis under drought stress.
AB  - Liquorice (Glycyrrhiza uralensis) is an important medicinal plant for which there
      is a huge market demand. It has been reported that arbuscular mycorrhizal (AM)
      symbiosis and drought stress can stimulate the accumulation of the active
      ingredients, glycyrrhizin and liquiritin, in liquorice plants, but the potential
      interactions of AM symbiosis and drought stress remain largely unknown. In the
      present work, we investigated mycorrhizal effects on plant growth and
      accumulation of glycyrrhizin and liquiritin in liquorice plants under different
      water regimes. The results indicated that AM plants generally exhibited better
      growth and physiological status including stomatal conductance, photosynthesis
      rate, and water use efficiency compared with non-AM plants. AM inoculation up
      regulated the expression of an aquaporin gene PIP and decreased root abscisic
      acid (ABA) concentrations under drought stress. In general, AM plants displayed
      lower root carbon (C) and nitrogen (N) concentrations, higher phosphorus (P)
      concentrations, and therefore, lower C:P and N:P ratios but higher C:N ratio than
      non-AM plants. On the other hand, AM inoculation increased root glycyrrhizin and
      liquiritin concentrations, and the mycorrhizal effects were more pronounced under
      moderate drought stress than under well-watered condition or severe drought
      stress for glycyrrhizin accumulation. The accumulation of glycyrrhizin and
      liquiritin in AM plants was consistent with the C:N ratio changes in support of
      the carbon-nutrient balance hypothesis. Moreover, the glycyrrhizin accumulation
      was positively correlated with the expression of glycyrrhizin biosynthesis genes
      SQS1, beta-AS, CYP88D6, and CYP72A154. By contrast, no significant interaction of
      AM inoculation with water treatment was observed for liquiritin accumulation,
      while we similarly observed a positive correlation between liquiritin
      accumulation and the expression of a liquiritin biosynthesis gene CHS. These
      results suggested that AM inoculation in combination with proper water management
      potentially could improve glycyrrhizin and liquiritin accumulation in liquorice
      roots and may be practiced to promote liquorice cultivation.

PMID- 29455338
TI  - Extracellular ATP is Differentially Metabolized on Papillary Thyroid Carcinoma
      Cells Surface in Comparison to Normal Cells.
AB  - The incidence of differentiated thyroid cancer has been increasing. Nevertheless,
      its molecular mechanisms are not well understood. In recent years, extracellular
      nucleotides and nucleosides have emerged as important modulators of tumor
      microenvironment. Extracellular ATP is mainly hydrolyzed by NTPDase1/CD39 and
      NTPDase2/CD39L1, generating AMP, which is hydrolyzed by ecto-5'-nucleotidase
      (CD73) to adenosine, a possible promoter of tumor growth and metastasis. There
      are no studies evaluating the expression and functionality of these
      ectonucleotidases on normal or tumor-derived thyroid cells. Thus, we investigated
      the ability of thyroid cancer cells to hydrolyze extracellular ATP generating
      adenosine, and the expression of ecto-enzymes, as compared to normal cells. We
      found that normal thyroid derived cells presented a higher ability to hydrolyze
      ATP and higher mRNA levels for ENTDP1-2, when compared to papillary thyroid
      carcinoma (PTC) derived cells, which had a higher ability to hydrolyze AMP and
      expressed CD73 mRNA and protein at higher levels. In addition, adenosine induced
      an increase in proliferation and migration in PTC derived cells, whose effect was
      blocked by APCP, a non-hydrolysable ADP analogue, which is an inhibitor of CD73.
      Taken together, these results showed that thyroid follicular cells have a
      functional purinergic signaling. The higher expression of CD73 in PTC derived
      cells might favor the accumulation of extracellular adenosine in the tumor
      microenvironment, which could promote tumor progression. Therefore, as already
      shown for other tumors, the purinergic signaling should be considered a potential
      target for thyroid cancer management and treatment.

PMID- 29455339
TI  - Analysis of COMT Val158Met polymorphisms and methylation in Chinese male
      schizophrenia patients with homicidal behavior.
AB  - Schizophrenia is a severe mental disorder, and its mechanisms have not been fully
      elucidated. A functional single nucleotide polymorphism (SNP) present in the
      catechol-O-methyltransferase (COMT) gene, Val158Met (rs4680) (Chr22: 19,963,498),
      is possibly related to the violent behavior of schizophrenia patients. However,
      the specific variant that causes violent behavior is still unknown. Since the Val
      variation of Val158Met (rs4680) introduces a CG site into the sequence, the
      methylation level of the Val158Met (rs4680) region may also have an association
      with the homicidal behavior of schizophrenia patients. A case-control study was
      conducted that included 100 normal males, 100 schizophrenia inpatients, and 100
      schizophrenia inpatients with homicidal behavior. A polymorphism of Val158Met
      (rs4680) and the methylation levels were analyzed by pyrosequencing. Compared to
      Met carriers, the Val/Val genotype was significantly associated with the
      homicidal behavior of schizophrenia patients. In addition, the methylation levels
      of the Val158Met (rs4680) region were significantly different between the three
      groups. Moreover, the methylation level of an rs4680-related CpG site was
      significantly associated with the Val/Val genotype which may contribute to the
      homicidal behavior of schizophrenia patients. In this study, we showed that the
      Val allele at Val158Met (rs4680) may be associated with the homicidal behavior of
      schizophrenia patients as well as that the methylation level of Val158Met
      (rs4680) could be affected by the variation of Val158Met (rs4680) and eventually
      contribute to the violent behavior of schizophrenia patients.

PMID- 29455340
TI  - An international clinical study of ability and disability in ADHD using the WHO
      ICF framework.
AB  - This is the fourth and final study designed to develop International
      Classification of Functioning, Disability and Health (ICF, and children and youth
      version, ICF-CY) core sets for attention-deficit hyperactivity disorder (ADHD).
      To investigate aspects of functioning and environment of individuals with ADHD as
      documented by the ICF-CY in clinical practice settings. An international cross
      sectional multi-centre study was applied, involving nine units from eight
      countries: Denmark, Germany, India, Italy, Portugal, Saudi Arabia, Sweden and
      Taiwan. Clinicians and clinical researchers rated the functioning level of 112
      children, adolescents and adults with ADHD using the extended ICF-CY checklist
      version 2.1a. The ratings were based on a variety of information sources, such as
      medical records, medical history, clinical observations, clinical questionnaires,
      psychometric tests and structured interviews with participants and family
      members. In total, 113 ICF-CY categories were identified, of which 50 were
      related to the activities and participation, 33 to environmental factors and 30
      to body functions. The clinical study also yielded strengths related to ADHD,
      which included temperament and personality functions and recreation and leisure.
      The study findings endorse the complex nature of ADHD, as evidenced by the many
      functional and contextual domains impacted in ADHD. ICF-CY based tools can serve
      as foundation for capturing various functional profiles and environmental
      facilitators and barriers. The international nature of the ICF-CY makes it
      possible to develop user-friendly tools that can be applied globally and in
      multiple settings, ranging from clinical services and policy-making to education
      and research.

PMID- 29455341
TI  - Do Callous-Unemotional Traits and Conduct Disorder Symptoms Predict the Onset and
      Development of Adolescent Substance Use?
AB  - Despite strong evidence of the relationship between conduct disorder (CD)
      symptoms and substance use, it is unclear how callous-unemotional (CU) traits
      predict substance use over and above CD symptoms, and their potential
      interaction. This study used data from 753 participants followed from grade 7 to
      2-years post-high school. Latent growth curve models showed that CU traits
      predicted the onset of cigarette use, alcohol misuse, and a substance use
      composite at grade 7 only when no CD symptoms were present. Among those without
      CD symptoms, boys showed greater change in the odds of using cigarettes, and were
      more likely to misuse alcohol or use any substance at grade 7 than girls.
      However, CD symptoms, CU traits, and their interaction did not predict the linear
      rates of growth of substance use over time. Thus, CU traits may uniquely predict
      adolescent substance use when CD symptoms are not present. This research has
      implications for predicting onset of adolescent substance use and for
      incorporating the assessment of CU traits into interventions targeting adolescent
      substance use.

PMID- 29455342
TI  - Pre-protective effects of dietary chitosan supplementation against oxidative
      stress induced by diquat in weaned piglets.
AB  - The protective effects of chitosan (CS) supplementations on oxidative stress
      induced by diquat in weaned piglets were investigated. A total of 36 crossbreed
      piglets with an average live body weight (BW) of 8.80 +/- 0.53 kg were weaned at
      28 +/- 2 days and randomly divided into six dietary treatments (n = 6): control
      (basal diet), negative control (10 mg diquat/kg BW injected to piglets fed with
      basal diet), and basal diet treatments containing either 250, 500, 1000, or 2000
      mg/kg of CS administered to piglets injected with 10 mg diquat/kg BW. The
      experiment conducted for 21 days which consisted of pre-starter period (14 days)
      and starter period (7 days). BW, feed intake, and fecal consistency were
      monitored. Blood samples were collected to determine antioxidative and immune
      parameters. CS supplementation improved the growth performance and decreased
      fecal score of piglets from days 1 to 14. Diquat also induced oxidative stress
      and inflammatory responses by decreasing the activities of antioxidant and
      regulating cytokines. But dietary CS alleviated these negative effects induced by
      diquat that showed decreasing serum concentrations of pro-inflammatory cytokines
      but increasing activities of antioxidant enzymes and anti-inflammatory cytokines.
      Results indicated that CS attenuated the oxidative stress of piglets caused by
      diquat injection.

PMID- 29455343
TI  - The first isolation of Westerdykella dispersa in a critically burned patient.
AB  - Patients with critical thermal trauma belong to one of the most high-risk groups
      for development of infectious complications. Fungal infections are not among
      frequent complications during therapy of patients with thermal trauma, yet their
      incidence dramatically aggravates the prognosis for patients with this disorder.
      In the case report, we present the case of a young man with a critical burn,
      where Westerdykella dispersa was isolated. Identification of the pathogen was
      provided with a combination of cultivation and molecular biological confirmation.
      In this case, the distinction between infection and colonization was very
      complicated. Histopathological examination for definitive diagnosis of infection
      was not performed because the material from unburned soft tissue sampling could
      further compromise the function of the hand. Repeated cultivation and molecular
      identification W. dispersa before and after the necrectomy is indicative of
      infection rather than colonization. It is the second documented case of positive
      cultivation with this pathogen in humans and the first such case in a non
      neutropenic host.

PMID- 29455344
TI  - Lower third molar displaced to lateral pharyngeal space after mandibular angle
      fracture: a case report.
AB  - The removal of displaced dental elements from deep anatomical spaces is a
      condition that requires the knowledge of the region and skills to perform the
      procedure. The lateral pharyngeal space contains important structures such as the
      internal carotid artery and close proximity with the cranium basis. The aim of
      this paper is to report a clinical case of a lower third molar displaced to the
      lateral pharyngeal space after a mandibular angle fracture and its treatment by
      surgical intervention. The tooth was removed under general anesthesia by direct
      approach and the fracture was reduced and fixed with a plate and screws. This
      case report illustrates the importance of an immediate procedure to avoiding
      severe complications and further damage to important anatomical structures.

PMID- 29455345
TI  - The Antidiabetic Armamentarium: Reducing the Residual Cardiovascular Risk with
      HbA1c(v)-Lowering Medications : Editorial to: "GLP-1 Receptor Agonists and
      Cardiovascular Disease: A Meta-Analysis of Recent Cardiac Outcome Trials" by Jia
      X, Alam M, Ye Y et al.

PMID- 29455346
TI  - History of orthopaedics in China: a brief review.
AB  - BACKGROUND AND PURPOSE: Chinese orthopaedic surgeons have made a substantial
      contribution to the development of orthopaedics worldwide, and traditional
      Chinese medicine (TCM) in orthopaedics has a very long history in China. We make
      a brief review of the development of orthopaedics in China, intending to pave the
      way for further understanding of Chinese orthopaedics for scholars all over the
      world. RESULTS: The description of fractures firstly appeared in 3600 years ago
      in China, and the theories, experience, and treatment strategies of TCM still
      play important roles in clinical diagnosis and treatment of orthopaedic disorders
      in our country. Western orthopaedics was first introduced into China in the early
      twentieth century. After decades of development, Chinese scholars have made some
      gratifying achievements in orthopaedics. CONCLUSIONS: Orthopaedics is constantly
      evolving, and we need to strengthen the ability of independent innovation to
      achieve orthopaedic surgeons' Chinese dream, and better serve our patients.

PMID- 29455347
TI  - A prospective comparative study of hip resurfacing arthroplasty and large
      diameter head metal-on-metal total hip arthroplasty in younger patients-a minimum
      of five year follow-up.
AB  - INTRODUCTION: Both hip resurfacing arthroplasty (HRA) and large-diameter head
      metal-on-metal total hip arthroplasty (LDH MoM THA) are generally used for young
      and active patients. A number of comparative studies of HRA and total hip
      arthroplasty have been published in the literature. However, studies that have
      compared HRA with LDH MoM THA are rare. The purpose of this study is to compare
      the mid-term results of HRA with those of LDH MoM THA in young patients. PATIENTS
      AND METHODS: Between 2007 and 2011, 68 patients were enrolled in the study and
      randomized into two groups: HRA group (28 hips) and LDH MoM THA group (40 hips).
      Peri-operative data including blood loss, surgery duration, size of the implant,
      and post-operative complications were recorded. All patients were assessed
      clinically and radiologically at six weeks; one, three and five years; and at the
      time of final review. Functional outcome were assessed using Harris hip (HHS),
      University of California Los Angeles (UCLA) and Oxford hip (OHS) scores. The mean
      follow-up for all patients was 7.4 years (5 to 9). RESULTS: Patient groups
      matched similarly in age, percent female, body mass index, preoperative HHS, and
      follow-up time. No differences were observed between the two groups in blood loss
      or in head size or acetabular inclination angle. HRA group had significantly
      longer surgery duration but less blood loss. The two groups had comparable HHS,
      UCLA, and OHS at the latest follow-up. Major complications, such as fracture,
      dislocation, infection, and adverse reactions to the metal debris (ARMD) were not
      found in the two groups. Only one case in LDH MoM THA group underwent revision
      surgery due to unexplained pain. CONCLUSION: Comparison of HRA and LDH MoM THA
      shows similar mid-term clinical results. HRA may be preferable due to the well
      preserved bone stock and restoration of the native anatomy. LDH MoM THA may be
      used with caution due to the excessive metal ion release.

PMID- 29455348
TI  - The effect of the anterior boundary of necrotic lesion on the occurrence of
      collapse in osteonecrosis of the femoral head.
AB  - PURPOSE: The location of the necrotic lesion is one of the important factors for
      collapse in osteonecrosis of the femoral head (ONFH). The significance of
      anterior localization has been little studied. This study evaluated the effects
      of anterior boundary of a necrotic lesion on collapse. METHODS: We reviewed the
      outcomes of 113 consecutive non-collapsed asymptomatic hips in 98 ONFH patients
      with mean follow-up of 4.7 years (2.0-11.8) after the initial magnetic resonance
      (MR) imaging. The presence or absence of collapse was investigated using follow
      up radiographs. The location of the anterior boundary of a necrotic lesion was
      assessed using the anterior necrotic angle between the midline of the femoral
      neck shaft and the line passing from the femoral head centre to the anterior
      boundary on mid-oblique MR imaging. Multivariate analysis was performed to
      identify risk factors for collapse, and further analyses were executed according
      to the lateral boundary of the necrotic lesion. RESULTS: During the follow-up
      period, collapse was confirmed in 61 hips (54.0%). Multivariate analysis revealed
      that the anterior necrotic angle was independently associated with collapse as
      well as the lateral boundary of the necrotic lesion. When the lateral boundary
      was located at the middle third of weight-bearing portion (32 hips), that was
      generally categorized as a low risk of collapse, all five cases with anterior
      necrotic angle >= 79 degrees  developed collapse, whereas only one of 27 cases
      (3.7%) with an anterior necrotic angle < 79 degrees  developed collapse (p <
      0.0001). CONCLUSIONS: This study indicates that ONFH patients with anterior
      localization of a necrotic lesion can develop collapse even if the necrotic
      lesion is medially located.

PMID- 29455349
TI  - Application of washed MSWI fly ash in cement composites: long-term environmental
      impacts.
AB  - In the present study, long-term environmental impacts of compact and ground
      cement composites, in which 30 wt.% of cement was replaced by washed municipal
      solid wastes incineration (MSWI) fly ash, were investigated for use in building
      industry. Consecutive leaching tests over a time span of 180 days were performed
      in acid water, deionized water, and saline water, respectively, with the
      accumulative concentration of different elements determined in the leachate.
      Different leaching behaviors are observed among different potential toxic
      elements (PTEs). For instance, higher concentrations of V in the leachate were
      observed from the compact cement composites than those from the ground ones. The
      concentration of Ba in the leachate increased with the decrease of particle size
      of the cement composites, and an initial increase in the leaching efficiency of
      Sn was followed by a clear decline with the leaching time. In addition, kinetic
      study revealed that the leaching behaviors of potential toxic elements follow a
      second-order model. The results demonstrated that the addition of washed MSWI fly
      ash into cement can contribute to the attrition resistance, indicating that the
      washed MSWI fly ash could be a promising alternative for cement as supplementary
      building materials.

PMID- 29455350
TI  - Analysing the accuracy of machine learning techniques to develop an integrated
      influent time series model: case study of a sewage treatment plant, Malaysia.
AB  - The function of a sewage treatment plant is to treat the sewage to acceptable
      standards before being discharged into the receiving waters. To design and
      operate such plants, it is necessary to measure and predict the influent flow
      rate. In this research, the influent flow rate of a sewage treatment plant (STP)
      was modelled and predicted by autoregressive integrated moving average (ARIMA),
      nonlinear autoregressive network (NAR) and support vector machine (SVM)
      regression time series algorithms. To evaluate the models' accuracy, the root
      mean square error (RMSE) and coefficient of determination (R2) were calculated as
      initial assessment measures, while relative error (RE), peak flow criterion (PFC)
      and low flow criterion (LFC) were calculated as final evaluation measures to
      demonstrate the detailed accuracy of the selected models. An integrated model was
      developed based on the individual models' prediction ability for low, average and
      peak flow. An initial assessment of the results showed that the ARIMA model was
      the least accurate and the NAR model was the most accurate. The RE results also
      prove that the SVM model's frequency of errors above 10% or below - 10% was
      greater than the NAR model's. The influent was also forecasted up to 44 weeks
      ahead by both models. The graphical results indicate that the NAR model made
      better predictions than the SVM model. The final evaluation of NAR and SVM
      demonstrated that SVM made better predictions at peak flow and NAR fit well for
      low and average inflow ranges. The integrated model developed includes the NAR
      model for low and average influent and the SVM model for peak inflow.

PMID- 29455352
TI  - Electrokinetic-Fenton remediation of organochlorine pesticides from historically
      polluted soil.
AB  - Soil contamination by persistent organic pollutants (POPs) poses a great threat
      to historically polluted soil worldwide. In this study, soils were characterized,
      and organochlorine pesticides contained in the soils were identified and
      quantified. Individual electrokinetic (IE), EK-Fenton-coupled technologies (EF),
      and enhanced EK-Fenton treatment (E-1, E-2, and E-3) were applied to remediate
      soils contaminated with hexachloro-cyclohexane soprocide (HCH) and dichloro
      diphenyl-trichloroethane (DDT). Variation of pH, electrical conductivity, and
      electroosmotic flow was evaluated during the EK-Fenton process. The IE treatment
      showed low removal efficiency for HCHs (30.5%) and DDTs (25.9%). In the EF
      treatment, the highest removal level (60.9%) was obtained for alpha-HCH, whereas
      P,P-DDT was the lowest (40.0%). Low solubility of pollutants impeded the HCH and
      DDT removal. After enhanced EK-Fenton treatment, final removal of pollutants
      decreased as follows: beta-HCH (82.6%) > gamma-HCH (81.6%) > alpha-HCH (81.2%) >
      delta-HCH (80.0%) > P,P-DDD (73.8%) > P,P-DDE (73.1%) > P,P-DDT (72.6%) > O,P-DDT
      (71.5%). The results demonstrate that EK-Fenton is a promising technology for POP
      removal in historically polluted soil.

PMID- 29455351
TI  - Lead facilitates foci formation in a Balb/c-3T3 two-step cell transformation
      model: role of Ape1 function.
AB  - Several possible mechanisms have been examined to gain an understanding on the
      carcinogenic properties of lead, which include among others, mitogenesis,
      alteration of gene expression, oxidative damage, and inhibition of DNA repair.
      The aim of the present study was to explore if low concentrations of lead,
      relevant for human exposure, interfere with Ape1 function, a base excision repair
      enzyme, and its role in cell transformation in Balb/c-3T3. Lead acetate 5 and 30
      MUM induced APE1 mRNA and upregulation of protein expression. This increase in
      mRNA expression is consistent throughout the chronic exposure. Additionally, we
      also found an impaired function of Ape1 through molecular beacon-based assay. To
      evaluate the impact of lead on foci formation, a Balb/c-3T3 two-step
      transformation model was used. Balb/c-3T3 cells were pretreated 1 week with low
      concentrations of lead before induction of transformation with n-methyl-n
      nitrosoguanidine (MNNG) (0.5 MUg/mL) and 12-O-tetradecanoylphorbol-13-acetate
      (TPA) (0.1 MUg/mL) (a classical two-step protocol). Morphological cell
      transformation increased in response to lead pretreatment that was paralleled
      with an increase in Ape1 mRNA and protein overexpression and an impairment of
      Ape1 activity and correlating with foci number. In addition, we found that lead
      pretreatment and MNNG (transformation initiator) increased DNA damage, determined
      by comet assay. Our data suggest that low lead concentrations (5, 30 MUM) could
      play a facilitating role in cellular transformation, probably through the
      impaired function of housekeeping genes such as Ape1, leading to DNA damage
      accumulation and chromosomal instability, one of the most important hallmarks of
      cancer induced by chronic exposures.

PMID- 29455353
TI  - Lethal and sub-lethal effects of cyproconazole on freshwater organisms: a case
      study with Chironomus riparius and Dugesia tigrina.
AB  - The fungicide cyproconazole (CPZ) inhibits the biosynthesis of ergosterol, an
      essential sterol component in fungal cell membrane and can also affect non-target
      organisms by its inhibitory effects on P450 monooxygenases. The predicted
      environmental concentration of CPZ is up to 49.05 MUg/L and 145.89 MUg/kg in
      surface waters and sediments, respectively, and information about CPZ toxicity
      towards non-target aquatic organisms is still limited. This study aimed to
      address the lack of ecotoxicological data for CPZ, and thus, an evaluation of the
      lethal and sub-lethal effects of CPZ was performed using two freshwater
      invertebrates (the midge Chironomus riparius and the planarian Dugesia tigrina).
      The estimated CPZ 48 h LC50 (95% CI) was 17.46 mg/L for C. riparius and 47.38
      mg/L for D. tigrina. The emergence time (EmT50) of C. riparius was delayed by CPZ
      exposure from 0.76 mg/L. On the other hand, planarians showed higher tolerance to
      CPZ exposure. Sub-lethal effects of CPZ on planarians included reductions in
      locomotion (1.8 mg/L), delayed photoreceptors regeneration (from 0.45 mg/L), and
      feeding inhibition (5.6 mg/L). Our results confirm the moderate toxicity of CPZ
      towards aquatic invertebrates but sub-lethal effects observed also suggest
      potential chronic effects of CPZ with consequences for population dynamics.

PMID- 29455354
TI  - Uptake and elimination kinetics of trifluralin and pendimethalin in Pheretima
      spp. and Eisenia spp.
AB  - The purpose of this study was to clarify the kinetic bioaccumulation potential of
      herbicides in the earthworm, Pheretima spp., the most common earthworms
      throughout Asia, and Eisenia spp., litter-feeding earthworms included in the test
      species recommended by the Organization for Economic Co-operation and
      Development. The kinetic bioaccumulation factors of trifluralin and pendimethalin
      were estimated from an uptake test for 10 or 12 days and from an elimination test
      for 10 days. The time required to reach a steady state following herbicide
      exposure was 7 days for both herbicides in Eisenia spp. and 1 day in Pheretima
      spp. The uptake rate constant (g-soil/g-worm/day) and elimination rate constant
      (per day) for trifluralin were 2.1 and 0.23 in Eisenia spp. and 0.42 and 0.45 in
      Pheretima spp., respectively, and those for pendimethalin were 1.5 and 0.26 in
      Eisenia spp. and 0.27 and 1.0 in Pheretima spp., respectively. Kinetic
      bioaccumulation factors of both herbicides were relatively close to
      bioaccumulation factors in steady state and were higher in Eisenia spp. (8.9 for
      trifluralin and 5.7 for pendimethalin) than in Pheretima spp. (0.95 and 0.26).
      These results demonstrated that the herbicide bioaccumulation risk is lower for
      Pheretima spp. than for Eisenia spp. because of the lower uptake rate and higher
      elimination rate in Pheretima spp.

PMID- 29455355
TI  - The combination of Luffa cylindrical fibers and metal oxides offers a highly
      performing hybrid fiber material in water decontamination.
AB  - The present investigation aims to prepare a hybrid material from Luffa cylindrica
      and metal oxides (ZnO, Al2O3) by precipitation for different percentages of zinc
      and aluminum (1, 2, and 4%) with a determined amount of biomass (a diameter of
      250 MUm). Physicochemical characterization of "Luffa cylindrica" and "Luffa
      cylindrica-metal oxides" was carried out by Boehm titration, pHPZC determination,
      scanning electron microscopy (SEM), and FTIR spectroscopic analysis. The process
      was optimized according to the adsorbed amount of methylene blue: MB (cationic
      dye) and methyl orange: MO (anionic dye) onto Luffa cylindrica and hybrid
      materials prepared. The results demonstrated the efficiency of the designed
      hybrid materials in removing MB and MO, accelerating the biosorption process and
      improving the performance of Luffa cylindrica fibers. The highest quantities
      adsorbed of dyes were obtained by the hybrid material prepared using 4% ZnO.
      Finally, the Brouers-Sotolongo mathematical modeling of kinetics was used in
      order to describe the pollutants retention process.

PMID- 29455356
TI  - A novel electrocatalytic approach for effective degradation of Rh-B in water
      using carbon nanotubes and agarose.
AB  - Carbon nanotubes (CNTs)/agarose (AG) membrane on the ITO (indium tin oxide)
      conductive glass, with high efficiency of electrocatalytic degradation for
      rhodamine B (Rh-B) in water, was prepared using an easy and green method. The
      prepared CNTs/AG membrane was characterized by scanning electron microscopy
      (SEM), X-ray diffraction (XRD), energy dispersive spectra (EDS), infrared
      spectroscopy (IR), and electrochemical impedance spectroscopy (EIS). The results
      revealed that CNTs were dispersed in the AG membrane. Additionally, the
      electrocatalytic activities for Rh-B were conducted on the electrochemical
      workstation with a three-electrode system. Both initial pH and potential played
      an important role in the process of electrocatalytic degradation. At pH 3 and
      potential reaching 4 V, the removal rate of Rh-B (10 mg/L) in water achieved 96%
      within 20 min. The stability of the prepared CNTs/AG membrane was also
      investigated. Besides, the toxicities of the main intermediates from the
      electrocatalytic degradation for Rh-B were calculated using the ECOSAR program
      and EPIWIN software, and results indicated that the toxicities of some
      intermediates were higher than those of the parent pollutant (Rh-B). These
      findings provided a light-spot to simplify the preparation of efficient working
      electrode and emphasized the possible potential risks from intermediates at the
      same time.

PMID- 29455357
TI  - Phytochemical constituents, antioxidant activity, and antiproliferative
      properties of black, red, and brown rice bran.
AB  - BACKGROUND: In the recent years, the health benefits of the pigmented rice
      varieties have reported due to the presence of bioactive compounds. In this
      study, the phytochemical constituents (total phenolic, flavonoid and anthocyanin
      content) and individual phenolics and flavonoids of the extracts of sixteen
      genotypes of pigmented rice bran were evaluated using spectrophotometric and
      ultra-high performance liquid chromatography method. Antioxidative properties of
      the free and bound fractions were evaluated using nitric oxide and 1,1-diphenyl-2
      picrylhydrazyl scavenging assays. Extracts were evaluated for antiproliferative
      activity against breast cancer cell lines (MCF-7 and MDA-MB-231) using the MTT
      assay. RESULTS: Signifficant diferences were observed in the concentrations of
      phytochemicals and biological activities among different pigmented rice brans.
      The highest phytochemical content was observed in black rice bran followed by red
      and brown rice bran. The concentration of free individual flavonoids and phenolic
      compounds were significantly higher than those of bound compounds except those of
      ferulic acid and p-coumaric acid. Highest antioxidant activities were observed in
      black rice bran, followed by red and brown rice bran extracts. Extracts of black
      rice bran exhibited potent antiproliferative activity, with half maximal
      inhibitory concentrations (IC50) of 148.6 and 119.2 mg/mL against MCF-7 and MDA
      MB-231 cell lines, respectively, compared to the activity of the extracts of red
      rice bran (175.0 and 151.0 mg/mL, respectively) and brown rice bran (382.3 and
      346.1 mg/mL, respectively). CONCLUSIONS: Black rice bran contains high levels of
      phytochemicals, and thus has potent pharmaceutical activity. This highlights
      opportunities for researcher to breed new genotypes of rice with higher
      nutritional values, which the food industry can use to develop new products that
      will compete in expanding functional food markets.

PMID- 29455360
TI  - Macro and micro geo-spatial environment consideration for landfill site selection
      in Sharjah, United Arab Emirates.
AB  - Waste management involves various procedures and resources for proper handling of
      waste materials in compliance with health codes and environmental regulations.
      Landfills are one of the oldest, most convenient, and cheapest methods to deposit
      waste. However, landfill utilization involves social, environmental,
      geotechnical, cost, and restrictive regulation considerations. For instance,
      landfills are considered a source of hazardous air pollutants that can cause
      health and environmental problems related to landfill gas and non-methanic
      organic compounds. The increasing number of sensors and availability of remotely
      sensed images along with rapid development of spatial technology are helping with
      effective landfill site selection. The present study used fuzzy membership and
      the analytical hierarchy process (AHP) in a geo-spatial environment for landfill
      site selection in the city of Sharjah, United Arab Emirates. Macro- and micro
      level factors were considered; the macro-level contained social and economic
      factors, while the micro-level accounted for geo-environmental factors. The
      weighted spatial layers were combined to generate landfill suitability and
      overall suitability index maps. Sensitivity analysis was then carried out to
      rectify initial theoretical weights. The results showed that 30.25% of the study
      area had a high suitability index for landfill sites in the Sharjah, and the most
      suitable site was selected based on weighted factors. The developed fuzzy-AHP
      methodology can be applied in neighboring regions with similar geo-natural
      conditions.

PMID- 29455359
TI  - Eosinophilic Esophagitis: an Important Comorbid Condition of Asthma?
AB  - Eosinophilic esophagitis and asthma are frequently found as comorbid conditions
      in children and adults along with other manifestations of atopic diathesis. These
      two conditions have similar T helper 2 responses-driven pathophysiology and share
      common management strategies such as using systemic corticosteroids and targeted
      anti-cytokine biologic therapies. Review of the literature finds that asthma is
      often a comorbid condition in eosinophilic esophagitis in both children and
      adults; however, the EoE-asthma relationship remains poorly characterized
      mechanistically and clinically. EoE and asthma commonly share several comorbid
      conditions such as allergic rhinitis and gastroesophageal reflux disease;
      therefore, addressing these comorbid conditions has the potential to improve
      and/or maintain control in both diseases. Similar to asthma, patients with EoE
      frequently demonstrate elevations in serum markers of atopy, including serum IgE
      levels, peripheral eosinophil counts, and T helper 2-related cytokines.
      Gastroesophageal reflux disease is thought to affect asthma through
      microaspirations, airway hyperresponsiveness, and increased vagal tone. The
      understanding of the relationship between gastroesophageal reflux and EoE is
      still evolving but seems to be bidirectional and interactive. In terms of
      treatment, similar classes of medications have been used in both EoE and asthma.
      In both children and adults, EoE remission can be achieved by food trigger
      avoidance and use of corticosteroids and biologic therapies. Asthma control is
      mostly achieved through inhaled corticosteroids, and long but biologic therapies
      are increasingly used in severe subsets of the disease. Significant clinical and
      mechanistic work needs to be accomplished to better understand the relationship
      between asthma, EoE, and their interaction with other allergic diseases.
      Understanding whether shared mechanisms exist can lead to the development of new
      diagnostic and therapeutic strategies. The following review examines the existing
      literature regarding prevalence, common comorbidities, and potential therapeutic
      approach and identifies gaps in knowledge and future directions.

PMID- 29455358
TI  - The Use of Biomarkers to Predict Aero-Allergen and Food Immunotherapy Responses.
AB  - The incidence of allergic conditions has continued to rise over the past several
      decades, with a growing body of research dedicated toward the treatment of such
      conditions. By driving a complex range of changes in the underlying immune
      response, immunotherapy is the only therapy that modulates the immune system with
      long-term effects and is presently utilized for the treatment of several atopic
      conditions. Recent efforts have focused on identifying biomarkers associated with
      these changes that may be of use in predicting patients with the highest
      likelihood of positive clinical outcomes during allergen immunotherapy (AIT),
      providing guidance regarding AIT discontinuation, and predicting symptomatic
      relapse and the need for booster AIT after therapy. The identification of such
      biomarkers in food allergy has the additional benefit of replacing oral food
      challenges, which are presently the gold standard for diagnosing food allergies.
      While several markers have shown early promise, research has yet to identify a
      marker that can invariably predict clinical response to AIT. Skin prick testing
      (SPT) and specific IgE have commonly been used as inclusion criteria for the
      initiation of AIT and prediction of reactions during subsequent allergen
      challenge; however, existing data suggests that changes in these markers are not
      always associated with clinical improvement and can be widely variable, reducing
      their utility in predicting clinical response. Similar findings have been
      described for the use of allergen-specific functional IgG4 antibodies, basophil
      activation and histamine release, and type 2 innate lymphoid cells. There appears
      to be a promising association between changes in the expression of dendritic cell
      associated markers, as well as the use of DNA promoter region methylation
      patterns in the prediction of allergy status following therapy. The cellular and
      molecular changes brought about by immunotherapy are still under investigation,
      but major strides in our understanding are being made.

PMID- 29455362
TI  - Predicting functional outcomes of posterior circulation acute ischemic stroke in
      first 36 h of stroke onset.
AB  - Posterior circulation acute ischemic stroke constitutes one-fourth of all
      ischemic strokes and can be efficiently quantified using the posterior
      circulation Alberta stroke program early computed tomography score (PC-ASPECTS)
      through diffusion-weighted imaging. We investigated whether the PC-ASPECTS and
      National Institutes of Health Stroke Scale (NIHSS) facilitate functional outcome
      prediction among Chinese patients with posterior circulation acute ischemic
      stroke. Participants were selected from our prospective stroke registry from
      January 1, 2015, to December 31, 2016. The baseline NIHSS score was assessed on
      the first day of admission, and brain magnetic resonance imaging was performed
      within 36 h after stroke onset. Simple and multiple logistic regressions were
      conducted to determine stroke risk factors and the PC-ASPECTS. Receiver operating
      characteristics (ROC) curve analysis was performed to compare the NIHSS and PC
      ASPECTS. Of 549 patients from our prospective stroke admission registry database,
      125 (22.8%) had a diagnosis of posterior circulation acute ischemic stroke. The
      optimal cutoff for the PC-ASPECTS in predicting outcomes was 7. The odds ratios
      of the PC-ASPECTS (<= 7 vs > 7) in predicting outcomes were 6.33 (p = 0.0002) and
      8.49 (p = 0.0060) in the univariate and multivariate models, respectively, and
      7.52 (p = 0.0041) in the aging group. On ROC curve analysis, the PC-ASPECTS
      demonstrated more reliability than the baseline NIHSS for predicting functional
      outcomes of minor posterior circulation stroke. In conclusion, both the PC
      ASPECTS and NIHSS help clinicians predict functional outcomes. PC-ASPECTS > 7 is
      a helpful discriminator for achieving favorable functional outcome prediction in
      posterior circulation acute ischemic stroke.

PMID- 29455361
TI  - Treatment of neuromyelitis optica with rituximab: a 2-year prospective
      multicenter study.
AB  - OBJECTIVE: Neuromyelitis optica (NMO) is a very severe autoimmune disorder of the
      central nervous system. It affects young subjects and has a poor prognosis both
      on a functional and vital level. Therefore, it is imperative to reduce the
      frequency of relapses. The purpose of this study was to evaluate the clinical and
      neuroradiological effectiveness of rituximab (RTX) on active forms of NMO.
      METHODS: We conducted a 2-year open prospective multicenter study that included
      32 patients treated with RTX at a dose of 375 mg/m2/week for 1 month. When the
      number of circulating CD19+ B cells reached 1%, a maintenance therapy was
      started, consisting of two infusions of 1 g of RTX, administered at a 15-day
      interval. The primary objective was to reduce the annual relapse rate (ARR), in
      comparison to that observed in the 2 years before treatment onset. RESULTS:
      Rituximab administration reduced the ARR from 1.34 to 0.56 (p = 0.0005). The
      average Expanded Disability Status Scale (EDSS) score significantly improved by
      1.1 point, from 5.9 (2-9) to 4.8 (0-9) after 2 years (p = 0.03). Anti-aquaporin-4
      antibodies' level predicted treatment failure (p = 0.03). Frequency of Gad+
      lesions in spinal cord decreased from 23.3 to 14.2%. RTX treatment did not
      prevent the death of three patients (treatment failure in two patients and acute
      myeloid leukemia in a patient previously treated with mitoxantrone). CONCLUSION:
      Rituximab is clinically effective in active forms of NMO, although few patients
      are resistant to the treatment.

PMID- 29455363
TI  - Predicting Autism Spectrum Disorder Using Domain-Adaptive Cross-Site Evaluation.
AB  - The advances in neuroimaging methods reveal that resting-state functional fMRI
      (rs-fMRI) connectivity measures can be potential diagnostic biomarkers for autism
      spectrum disorder (ASD). Recent data sharing projects help us replicating the
      robustness of these biomarkers in different acquisition conditions or
      preprocessing steps across larger numbers of individuals or sites. It is
      necessary to validate the previous results by using data from multiple sites by
      diminishing the site variations. We investigated partial least square regression
      (PLS), a domain adaptive method to adjust the effects of multicenter acquisition.
      A sparse Multivariate Pattern Analysis (MVVPA) framework in a leave one site out
      cross validation (LOSOCV) setting has been proposed to discriminate ASD from
      healthy controls using data from six sites in the Autism Brain Imaging Data
      Exchange (ABIDE). Classification features were obtained using 42 bilateral
      Brodmann areas without presupposing any prior hypothesis. Our results showed that
      using PLS, SVM showed poorer accuracies with highest accuracy achieved (62%) than
      without PLS but not significantly. The regions occurred in two or more
      informative connections are Dorsolateral Prefrontal Cortex, Somatosensory
      Association Cortex, Primary Auditory Cortex, Inferior Temporal Gyrus and
      Temporopolar area. These interrupted regions are involved in executive function,
      speech, visual perception, sense and language which are associated with ASD. Our
      findings may support early clinical diagnosis or risk determination by
      identifying neurobiological markers to distinguish between ASD and healthy
      controls.

PMID- 29455364
TI  - Hyperirisinemia is independently associated with subclinical hypothyroidism:
      correlations with cardiometabolic biomarkers and risk factors.
AB  - PURPOSE: Irisin, a newly discovered adipo-myokine, is implicated in the
      modulation of the adipose phenotype, increasing energy expenditure and
      ameliorating systemic metabolism. Our aim was to investigate circulating irisin
      in subclinical hypothyroidism (SH) and study its associations with
      cardiometabolic risk factors. METHODS: In a large case-control study, serum
      irisin, insulin resistance and lipid parameters, classic adipokines, inflammatory
      and hepatic biomarkers, and cardiovascular risk factors were determined in 120
      consecutive patients with SH and 120 healthy controls matched on age, gender, and
      date of blood draw. Sixteen patients with SH received L-T4 treatment and, after 6
      months, serum irisin and other biomarkers were assessed. RESULTS: SH cases
      exhibited significantly higher circulating irisin than controls (p < 0.001). In
      all participants, irisin was positively associated with TSH, anti-TG, HOMA-IR, C
      peptide, lipid and inflammatory biomarkers, leptin, and cardiovascular risk
      factors, including Framigham score and apolipoprotein B/apolipoprotein A-I.
      Irisin was negatively correlated with adiponectin, HDL-C, and thyroid hormones.
      Serum irisin was independently associated with SH, above and beyond body mass
      index and cardiometabolic factors (p = 0.02). TSH was an independent predictor of
      circulating irisin (p = 0.003). L-T4 therapy did not reverse considerably the
      hyperirisinemic status in treated SH patients (p = 0.09). CONCLUSIONS: Irisin may
      represent an adipo-myokine counterbalancing a potential, gradual deterioration of
      lipid metabolism and insulin sensitivity in SH as well as reflecting a protective
      compensatory mechanism against oxidative muscle and thyroid cell stress. More
      mechanistic and prospective studies shedding light on the pathogenetic role of
      irisin in SH are needed to confirm and extend these data.

PMID- 29455365
TI  - Gender-differences in glycemic control and diabetes related factors in young
      adults with type 1 diabetes: results from the METRO study.
AB  - PURPOSE: To describe gender differences concerning glycemic control,
      cardiovascular risk factors, diabetic complications, concomitant pathologies, and
      circulating endothelial progenitor cells (EPCs), in a population of young adults
      with type 1 diabetes. METHODS: We collected data from 300 consecutively patients
      (168 males and 132 females), aged 18-30 years, among those admitted at Diabetes
      Unit of University of Campania "Luigi Vanvitelli" (Naples, Italy) from March 2012
      to January 2017. Circulating levels of seven EPCs phenotypes were determined by
      flow cytometry. RESULTS: As compared to men, women with type 1 diabetes had a
      significantly higher HbA1c levels (%, 8.4 +/- 1.3 vs. 8.1 +/- 1.3, P = 0.020),
      body mass index (Kg/m2, 24.8 +/- 4.2 vs. 23.9 +/- 3.9, P = 0.034), HDL
      cholesterol (mg/dL, 61.7 +/- 13.7 vs. 54.7 +/- 13.9, P < 0.001), and a lower
      count of both CD133+KDR+ and CD34+KDR+CD133+ EPCs (P = 0.022, P < 0.001,
      respectively). A higher proportion of women had overweight/obesity, and
      thyroiditis; smoking and sexual dysfunctions were more prevalent in men than in
      women. CONCLUSIONS: Young adults with type 1 diabetes present gender differences
      with regard to glycemic control, prevalence of some cardiovascular risk factors,
      sexual dysfunctions and circulating levels of EPCs, most often to the detriment
      of women.

PMID- 29455366
TI  - Phospholipase Ddelta assists to cortical microtubule recovery after salt stress.
AB  - The dynamic microtubule cytoskeleton plays fundamental roles in the growth and
      development of plants including regulation of their responses to environmental
      stress. Plants exposed to hyper-osmotic stress commonly acclimate, acquiring
      tolerance to variable stress levels. The underlying cellular mechanisms are
      largely unknown. Here, we show, for the first time, by in vivo imaging approach
      that linear patterns of phospholipase Ddelta match the localization of
      microtubules in various biological systems, validating previously predicted
      connection between phospholipase Ddelta and microtubules. Both the microtubule
      and linear phospholipase Ddelta structures were disintegrated in a few minutes
      after treatment with oryzalin or salt. Moreover, by using immunofluorescence
      confocal microscopy of the cells in the root elongation zone of Arabidopsis, we
      have shown that the cortical microtubules rapidly depolymerized within 30 min of
      treatment with 150 or 200 mM NaCl. Within 5 h of treatment, the density of
      microtubule arrays was partially restored. A T-DNA insertional mutant lacking
      phospholipase Ddelta showed poor recovery of microtubule arrays following salt
      exposition. The restoration of microtubules was significantly retarded as well as
      the rate of root growth, but roots of overexpressor GFP-PLDdelta prepared in our
      lab, have grown slightly better compared to wild-type plants. Our results
      indicate that phospholipase Ddelta is involved in salt stress tolerance, possibly
      by direct anchoring and stabilization of de novo emerging microtubules to the
      plasma membrane, providing novel insight into common molecular mechanism during
      various stress events.

PMID- 29455367
TI  - Adolescents and Young Adults Living with Congenital Heart Disease: Coping, Stress
      Reactivity, and Emotional Functioning.
AB  - Living with congenital heart disease (CHD) presents survivors with numerous
      stressors, which may contribute to emotional problems. This study examined (a)
      whether coping with CHD-related stress predicts symptoms of depression and
      anxiety, and (b) whether associations between coping and emotional distress are
      moderated by involuntary stress reactivity. Adolescents and young adults
      diagnosed with CHD (Mage = 26.4) were recruited from pediatric and adult
      outpatient cardiology clinics. Participants (N = 168) completed online self
      report measures. Hierarchical multiple regression analyses revealed that
      secondary control coping (e.g., cognitive restructuring, positive thinking)
      predicted lower depression and anxiety. Primary control coping (e.g., problem
      solving) and stress reactivity (e.g., rumination, emotional numbing) interacted
      to predict depression and anxiety: the higher individuals were in involuntary
      stress reactivity, the stronger was the association between primary control
      coping and lower depression and anxiety. These results can inform clinical
      efforts to prevent or reduce emotional distress among CHD survivors.

PMID- 29455368
TI  - Sepsis calculator implementation reduces empiric antibiotics for suspected early
      onset sepsis.
AB  - : Significant overtreatment with antibiotics for suspected early onset sepsis
      (EOS) constitutes a persisting clinical problem, generating unnecessary risks,
      harms, and costs for many newborns. We aimed to study feasibility and impact of a
      sepsis calculator to help guide antibiotic for suspected EOS in a European
      setting. In this single-center study, the sepsis calculator was implemented as an
      addition to and in accordance with existing protocols. One thousand eight hundred
      seventy-seven newborns >= 35 weeks of gestational age were prospectively
      evaluated; an analogous retrospective control group (n = 2076) was used for
      impact analysis. We found that empirical treatment with intravenous antibiotics
      for suspected EOS was reduced from 4.8 to 2.7% after sepsis calculator
      implementation (relative risk reduction 44% (95% confidence interval 21.4
      59.5%)). No evidence for changes in time to treatment start, treatment duration,
      or proven sepsis rates was found. Adherence to sepsis calculator recommendation
      was 91%. CONCLUSION: Pragmatic and feasible implementation of the sepsis
      calculator yields a 44% reduction of empirical use of antibiotics for EOS,
      without signs of delay or prolongation of treatment. These findings warrant a
      multicenter, nation-wide, randomized study evaluating systematic use of the
      sepsis calculator prediction model and its effects in clinical practice outside
      of the USA. What is known: * Significant overtreatment with antibiotics for
      suspected early-onset sepsis results in unnecessary costs, risks, and harms. *
      Implementation of the sepsis calculator in the USA has resulted in a significant
      decrease in empirical antibiotic treatment, without apparent adverse events. What
      is new: * Implementation of the sepsis calculator in daily clinical decision
      making in a Dutch teaching hospital is feasible in conjunction with existing
      protocols, with high adherence. * Antibiotic therapy for suspected early-onset
      sepsis was reduced by 44% following implementation of the calculator.

PMID- 29455369
TI  - Intradural spinal tumors in adults-update on management and outcome.
AB  - Among spinal tumors that occur intradurally, meningiomas, nerve sheath tumors,
      ependymomas, and astrocytomas are the most common. While a spinal MRI is the
      state of the art to diagnose intradural spinal tumors, in some cases CT scans,
      angiography, CSF analyses, and neurophysiological examination can be valuable.
      The management of these lesions depends not only on the histopathological
      diagnosis but also on the clinical presentation and the anatomical location,
      allowing either radical resection as with most extramedullary lesions or less
      invasive strategies as with intramedullary lesions. Although intramedullary
      lesions are rare and sometimes difficult to manage, well-planned treatment can
      achieve excellent outcome without treatment-related deficits. Technical advances
      in imaging, neuromonitoring, minimally invasive approaches, and radiotherapy have
      improved the outcome of intradural spinal tumors. However, the outcome in
      malignant intramedullary tumors remains poor. While surgery is the mainstay
      treatment for many of these lesions, radiation and chemotherapy are of growing
      importance in recurrent and multilocular disease. We reviewed the literature on
      this topic to provide an overview of spinal cord tumors, treatment strategies,
      and outcomes. Typical cases of extra- and intramedullary tumors are presented to
      illustrate management options and outcomes.

PMID- 29455370
TI  - Incomplete copolymer degradation of in situ chemotherapy.
AB  - In situ carmustine wafers containing 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)
      are commonly used for the treatment of recurrent glioblastoma to overcome the
      brain-blood barrier. In theory, this chemotherapy diffuses into the adjacent
      parenchyma and the excipient degrades in maximum 8 weeks but no clinical data
      confirms this evolution, because patients are rarely operated again. A 75-year
      old patient was operated twice for recurrent glioblastoma, and a carmustine wafer
      was implanted during the second surgery. Eleven months later, a third surgery was
      performed, revealing unexpected incomplete degradation of the wafer. 1H-Nuclear
      Magnetic Resonance was performed to compare this wafer to pure BCNU and to an
      unused copolymer wafer. In the used wafer, peaks corresponding to hydrophobic
      units of the excipient were no longer noticeable, whereas peaks of the
      hydrophilic units and traces of BCNU were still present. These surprising results
      could be related to the formation of a hydrophobic membrane around the wafer,
      thus interfering with the expected diffusion and degradation processes. The
      clinical benefit of carmustine wafers in addition to the standard radio
      chemotherapy remains limited, and in vivo behavior of this treatment is not
      completely elucidated yet. We found that the wafer may remain after several
      months. Alternative strategies to deal with the blood-brain barrier, such as drug
      loaded liposomes or ultrasound-opening, must be explored to offer larger drug
      diffusion or allow repetitive delivery.

PMID- 29455371
TI  - Cyclic fatigue resistance of R-Pilot, WaveOne Gold Glider, and ProGlider glide
      path instruments.
AB  - OBJECTIVE: The aim of the present study was to compare the cyclic fatigue
      resistance of R-Pilot (VDW; Munich, Germany) with ProGlider (Denstply Sirona;
      Ballaigues, Switzerland) and WaveOne Gold Glider (Denstply Sirona; Ballaigues,
      Switzerland) glide path instruments. MATERIALS AND METHODS: R-Pilot, ProGlider,
      and WaveOne Gold Glider instruments were collected (n = 15) and tested in a
      dynamic cyclic fatigue test device, which has an artificial canal with 60 degrees
      angle of curvature and a 5-mm radius of curvature. All instruments were operated
      until fracture occurred, and both time to fracture (TF) and the lengths of the
      fractured fragments were recorded. Mean and standard deviations of TF and
      fragment length were calculated for each reciprocating system. TF data and
      fractured fragment length data were subjected to one-way ANOVA and post-hoc Tukey
      tests (P < 0.05). Also a Weibull analysis was performed on TF data. RESULTS: The
      cyclic fatigue resistance values of the WaveOne Gold Glider and R-Pilot were
      significantly higher than those of the ProGlider (P < 0.05), with no significant
      difference between them (P > 0.05). Weibull analysis revealed that WaveOne Gold
      Glider showed the highest predicted TF value for 99% survival rate, which was
      followed by R-Pilot and ProGlider. Regarding the length of the fractured tips,
      there were no significant differences among the instruments (P > 0.05).
      CONCLUSIONS: The reciprocating WaveOne Gold Glider and R-Pilot instruments had
      significantly higher cyclic fatigue resistance than rotary ProGlider instruments.
      CLINICAL RELEVANCE: This study reported that novel reciprocating glide path
      instruments exhibited higher cyclic fatigue resistance than rotating glide path
      instrument.

PMID- 29455372
TI  - Effectiveness and effect of non-vital bleaching on the quality of life of
      patients up to 6 months post-treatment: a randomized clinical trial.
AB  - OBJECTIVES: The aim of this study was to evaluate the esthetic perception of
      patients at 6 months after bleaching of non-vital teeth with 35% of hydrogen
      peroxide and 37% of carbamide peroxide using a walking bleach technique. We also
      assessed psychosocial impacts as well as the clinical effectiveness and stability
      of the color change. MATERIALS AND METHODS: The teeth bleaching treatment was
      randomly assigned to two groups according to the bleaching agent used: G1 HP =
      35% of hydrogen peroxide (n = 25) and G2 CP = 37% of carbamide peroxide (n = 25).
      The non-vital bleaching was performed in four sessions using the walking bleach
      technique. The color was objectively (DeltaE) and subjectively (DeltaSGU)
      evaluated. The esthetic perception and psychosocial factors were evaluated before
      treatment as well as one and 6 months post-treatment using Oral Health Impact
      Profile (OHIP) esthetics and Psychosocial Impact of Dental Esthetics
      Questionnaire (PIDAQ). RESULTS: The color change (DeltaE) at 6 months (G1 = 14.53
      +/- 5.07 and G2 = 14.09 +/- 6.61) for both color groups remained stable until the
      6-month post-treatment (p > 0.05). There was a decrease in the values of OHIP
      esthetics and PIDAQ after treatment compared to the baseline (p < 0.05), and this
      effect was maintained 6 months post-treatment. CONCLUSIONS: Both agents were
      highly effective and maintained the color stability at 6 months; this positively
      affected the esthetic perception and psychosocial impact of patients who also
      remained stable over time. CLINICAL RELEVANCE: Non-vital bleaching produces a
      positive and stable impact on the esthetic perception and psychosocial factors at
      medium-term follow-ups.

PMID- 29455373
TI  - Diagnostic value of ultrasonography for the detection of disc displacements in
      the temporomandibular joint: a systematic review and meta-analysis.
AB  - OBJECTIVES: The aim was to assess the added diagnostic value of ultrasonography
      (US) for establishing the presence or absence of disc displacements (DDs) in
      temporomandibular joints (TMJs). MATERIALS AND METHODS: Pubmed and EMBASE were
      searched electronically to identify diagnostic accuracy studies that assessed the
      diagnostic value of US for the diagnosis of DD, using Magnetic resonance imaging
      (MRI) as the reference standard. Meta-analyses were performed with Metadisc 1.4
      and RevMan 5.3. RESULTS: A total of 16 studies qualified for meta-analyses. For
      the diagnosis of DD at closed mouth position (DD-CM) and DD at maximum mouth
      opening position (DD-MMO), the added values of a positive result with US for
      ruling in DD-CM and DD-MMO were 22 and 41%, while those of a negative result with
      US for ruling out DD-CM and DD-MMO were 30 and 20%. For the diagnosis of DD with
      reduction (DDWR) and DD without reduction (DDWoR), the added values of a positive
      result in US for ruling in DDWR and DDWoR were 35 and 41%, while those of a
      negative result in US for ruling out DDWR and DDWoR were 21 and 27%. CONCLUSIONS:
      Using MRI as reference standard, the added values of both positive predictive
      values and negative predictive values of US for ruling in and ruling out DDs are
      sufficient in the decision-making in dental practice. CLINICAL RELEVANCE: US can
      be a good imaging tool to supplement clinical examination findings in patients
      with suspected DDs. Combined static and dynamic examinations using high
      resolution US should be preferred.

PMID- 29455374
TI  - The earnings and employment losses before entering the disability system.
AB  - Although a number of papers in the literature have shown the employment and wage
      differences between individuals receiving disability benefits and non-disabled
      individuals, not much is known about the potential employment and wage losses
      that disabled individuals suffer before being officially accepted into the
      disability insurance system (DI). Therefore, in this paper we compare individuals
      that enter into the DI system due to a progressive deterioration in the health
      status (ordinary illness) to similar non-disabled individuals. Our aim is to
      identify the differences in employment and wages between these two groups before
      disabled individuals are officially accepted into the DI system. We combine
      matching models and difference-in-difference and we find that the wage
      (employment) growth patterns of both groups of workers become significantly
      different three (five) years before entering the DI system. More specifically,
      our estimates suggest that 1 year before entering the system, there is a
      difference of 79 Euros/month in the wages of the two groups (8.3% of average
      wage) as well as a 7.8% point difference in employment probabilities.

PMID- 29455375
TI  - Severe Mycoplasma Pneumonia in Child with Bilateral Parapneumonic Effusion
      Successfully Treated with Integrated Chinese and Western Medicine: A Case Report.

PMID- 29455376
TI  - Human Urine Extract Cell Differentiation Agent 2 Protects PC12 Cells from Serum
      Deprivation-Induced Apoptosis Accompanied with Priming of Extracellular Signal
      Regulated Kinase Activation and Differentiation Induction.
AB  - OBJECTIVE: To investigate the potential neuroprotective effect of human urine
      extract cell differentiation agent 2 (CDA-2) by the model of serum deprivation
      induced apoptosis of PC12 cells and study the underlying molecular mechanisms.
      METHODS: Apoptosis of PC12 cells was induced by serum deprivation. CDA-2 at doses
      of 0.5-4 mg/mL was used to treat the serum-deprived PC12 cells. The cellular
      viability was measured by sulforhodamine B binding assay and the cell apoptosis
      was determined by flow cytometer. Western blot was used to analyze the expression
      of differentiation markers and activity of extracellular signal-regulated kinase
      (ERK). The cellular morphology was examined under an inverted microscope.
      RESULTS: CDA-2 inhibited apoptotic cell death of serum-deprived PC12 cells in a
      dose-dependent manner. Expression of low- and mid-sized neurofilaments was
      observed in serum-deprived PC12 cells treated with CDA-2 or nerve growth factor
      (NGF). However, CDA-2 did not induce proliferation of these cells like NGF. The
      morphology of CDA-2 treated cells was changed from rounded to neuron-like flat
      polygonal shape in contrast to the extensive neurite outgrowth induced by NGF.
      CDA-2 transiently induced the phosphorylation of ERK in serum deprived-PC12 cells
      and the expression of neurofilaments induced by CDA-2 was attenuated by mitogen
      activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor
      PD98059. CONCLUSIONS: Human urine extract CDA-2 showed a potential
      neuroprotective activity which may correlate with ERK activation and
      differentiation induction.

PMID- 29455377
TI  - Prevalence of bacterial vaginosis in pregnant and non-pregnant Iranian women: a
      systematic review and meta-analysis.
AB  - PURPOSE: Bacterial vaginosis (BV) is a vaginal disorder which occurs either
      symptomatic or asymptomatic because of an imbalance between H2O2-producing
      Lactobacillus and Gardnerella vaginalis in the vagina. This systematic review and
      meta-analysis is the first to determine the prevalence of BV in pregnant and non
      pregnant women in Iran. METHODS: We used national (SID, Irandoc, Iranmedex and
      Magiran) and international (PubMed, Scopus, Google Scholar and ISI web of
      knowledge) electronic databases to systematically search and collect available
      studies using related keywords (up to 1 December 2017). Inclusion and exclusion
      criteria were defined to select eligible studies. RESULTS: The overall prevalence
      of BV among Iranian women was 18.9% (95% CI 14-25). Gardnerella vaginalis was the
      most prevalent isolated bacteria. The prevalence of BV in non-pregnant women was
      28% (95% CI 15.1-45.9) which was higher compared with pregnant women who had a
      prevalence of 16.5% (95% CI 12.5-21.6). CONCLUSION: The present review revealed a
      high prevalence of BV in non-pregnant women. Given that BV is associated with a
      series of reproductive complications such as infertility, taking preventive
      measures such as awareness of patients as well as monitoring and controlling of
      syndrome are essential.

PMID- 29455378
TI  - Age-Related Hearing Impairment Associated NAT2, GRM7, GRHL2 Susceptibility Gene
      Polymorphisms and Haplotypes in Roma and Hungarian Populations.
AB  - Age-related hearing impairment (ARHI) is the most frequent sensory disease in the
      elderly, which is caused by an interaction between genetic and environmental
      factors. Here we examined the ethnic differences, allele and genotype frequencies
      of the NAT2, GRM7, and GRHL2 genes pooled samples of healthy Hungarian and
      healthy and hearing impaired Roma people. Study populations of healthy Hungarian
      and Roma subjects were characterized for the rs1799930 NAT2, rs11928865 GRM7,
      rs10955255, rs13263539, and rs1981361 GRHL2 polymorphisms and deaf Roma subjects
      were characterized for the rs1799930 NAT2, rs13263539, and rs1981361 GRHL2 using
      a PCR-RFLP method. We found significant differences in minor allele frequencies
      for GRHL2 rs13263539 and rs1981361 polymorphism between healthy Roma and
      Hungarian samples (37.9% vs. 51.0% and 43.6% vs. 56.2%, respectively; p < 0.05).
      The differences of homozygous genotype of GRHL2 rs13263539 and rs1981361
      variants, values were also significantly different (13.0% vs. 25.3% and 16.5 vs.
      32.3%; p < 0.05). The NAT2 rs1799930 homozygous genotype was 14.0% in healthy
      Romas and 7.7% in Hungarians, while the minor A allele frequency was 38.0% and
      26.7% in Roma and Hungarian population, respectively (p < 0.05). Furthermore, the
      frequency of GGT, GAC and GAT haplotypes was significantly higher in the
      Hungarian population than in healthy Roma (1.87 vs. 4.47%, 0.91 vs. 2.07% and
      1.15 vs. 5.51%, respectively; p < 0.008). Present study revealed significant
      interethnic differences in allele polymorphisms of NAT2, GRM7 and GRHL2 exhibit
      quite marked ethnic differences in Roma populations that might have important
      implications for the preventive and therapeutic treatments in this population.

PMID- 29455379
TI  - Comparative Study of Different Classification Models in Renal-Cell Carcinoma.
AB  - The aim of this study was to compare the Memorial Sloan-Kettering Cancer Center
      (MSKCC) and the Cleveland Clinic Foundation (CCF) models of classification of
      aRCC patients. In addition, the model developed from the pivotal trial of
      temsirolimus and those proposed by Motzer et al. in 2004, Escudier et al., Heng
      et al., Choueiri et al. and Bamias et al. were examined. An observational,
      retrospective study of patients starting first-line systemic therapy was
      conducted between 2008 and 2011. The variables used to evaluate the
      classification models were median overall survival (mOS) and median progression
      free survival (mPFS). The comparison of different classification models was
      performed by comparing the area under the ROC (Receiver Operating Characteristic)
      curve (AUC) for time-dependent variables proposed by Heagerty. Eighty-eight
      patients were included. When the different models were compared, it was found
      that although based on the mOS, the Escudier model had better short-term (1-year)
      prognostic value, followed by the Heng model; in the long term, the models that
      presented a higher prognosis capacity were the Hudes and CCF models, closely
      followed by the Heng model. In addition, the Heng model had a slightly higher
      predictive ability than the other models. Based on the results, and in line with
      the European society for medical oncology (ESMO) guidelines, it appears that the
      model of Heng could be the best model to classify patients with aRCC and combines
      good short- and long-term prognostics while possessing better predictive ability
      and a more equal distribution of patients.

PMID- 29455380
TI  - Clinical features and peripartum outcomes in pregnant women with cardiac disease:
      a nationwide retrospective cohort study in Japan.
AB  - Although the number of pregnancies in women with cardiac disease is increasing
      worldwide, there are few data concerning their clinical characteristics and
      peripartum outcomes. Using the Diagnosis Procedure Combination database between
      2008 and 2014 in Japan, we retrospectively identified pregnant women who
      underwent high-risk delivery due to obstetric or non-obstetric comorbidities. We
      classified eligible women into those with pre-existing cardiac disease (cardiac
      disease group) and those with non-cardiac comorbidities (non-cardiac disease
      group) and compared their characteristics and peripartum outcomes. Of 94,364
      women undergoing high-risk delivery at 556 hospitals, 857 (0.91%) had pre
      existing cardiac disease (302, congenital heart disease; 190, arrhythmia; 176,
      valvular heart disease; 120, ischemic heart disease; 65, cardiomyopathy; 4,
      pericardial disease). Women in the cardiac disease group were more likely to be
      treated at university hospitals (51.1 versus 28.6%; p < 0.001) and in intensive
      care units (33.5 versus 18.8%; p < 0.001) than those in the non-cardiac disease
      group. The proportion of cesarean deliveries was 69.4% (emergency, 28.4%;
      elective, 41.1%) in the cardiac disease group and 73.4% (emergency, 38.4%;
      elective, 35.0%) in the non-cardiac disease group. Epidural analgesia during
      vaginal delivery was used significantly more frequently in the cardiac disease
      than non-cardiac disease group (15.6 versus 2.3%; p < 0.001). Heart failure
      occurred more frequently in the cardiac disease than the non-cardiac disease
      group (10.2 versus 0.3%; p < 0.001). In cardiac subgroup comparisons, heart
      failure occurred more frequently in women with congenital heart disease (12.3%),
      valvular heart disease (12.5%), or cardiomyopathy (12.3%) than in women with
      arrhythmia (6.3%) or ischemic heart disease (5.8%). Multivariable logistic
      regression analysis showed a significant positive association between pre
      existing cardiac disease and risk of heart failure (adjusted odds ratio, 24.7;
      95% confidence interval, 17.6-34.6; p < 0.001). No woman in the cardiac disease
      group died, whereas 18 women (0.02%) in the non-cardiac disease group did (p =
      1.000). These findings suggest that pregnant women with pre-existing cardiac
      disease are at a higher risk of heart failure during the peripartum period than
      those with non-cardiac comorbidities.

PMID- 29455381
TI  - Groundwater potential mapping using C5.0, random forest, and multivariate
      adaptive regression spline models in GIS.
AB  - Ever increasing demand for water resources for different purposes makes it
      essential to have better understanding and knowledge about water resources. As
      known, groundwater resources are one of the main water resources especially in
      countries with arid climatic condition. Thus, this study seeks to provide
      groundwater potential maps (GPMs) employing new algorithms. Accordingly, this
      study aims to validate the performance of C5.0, random forest (RF), and
      multivariate adaptive regression splines (MARS) algorithms for generating GPMs in
      the eastern part of Mashhad Plain, Iran. For this purpose, a dataset was produced
      consisting of spring locations as indicator and groundwater-conditioning factors
      (GCFs) as input. In this research, 13 GCFs were selected including altitude,
      slope aspect, slope angle, plan curvature, profile curvature, topographic wetness
      index (TWI), slope length, distance from rivers and faults, rivers and faults
      density, land use, and lithology. The mentioned dataset was divided into two
      classes of training and validation with 70 and 30% of the springs, respectively.
      Then, C5.0, RF, and MARS algorithms were employed using R statistical software,
      and the final values were transformed into GPMs. Finally, two evaluation criteria
      including Kappa and area under receiver operating characteristics curve (AUC-ROC)
      were calculated. According to the findings of this research, MARS had the best
      performance with AUC-ROC of 84.2%, followed by RF and C5.0 algorithms with AUC
      ROC values of 79.7 and 77.3%, respectively. The results indicated that AUC-ROC
      values for the employed models are more than 70% which shows their acceptable
      performance. As a conclusion, the produced methodology could be used in other
      geographical areas. GPMs could be used by water resource managers and related
      organizations to accelerate and facilitate water resource exploitation.

PMID- 29455382
TI  - QSPR modeling of optical rotation of amino acids using specific quantum chemical
      descriptors.
AB  - Many chemical phenomena occur in solution. Different solvents can change the
      optical activity of chiral molecules. The optical rotation angles of solutes of
      75 amino acids in dimethylformamide, water and methanol were analyzed using the
      quantitative structure-activity relationships approach. For an accurate
      description of chirality, we used specific quantum chemical descriptors, which
      reflect the properties of a chiral center, and continuous symmetry measures. The
      set of specific quantum chemical descriptors for atoms located near the chiral
      center, such as Mulliken charges, the sum of Mulliken charges on an atom (with
      the hydrogen charges summed up with the adjacent non-hydrogen atoms), and nuclear
      magnetic resoncance tensors was applied. To represent solvent effects, we used
      mixture-like structural simplex descriptors and quantum chemical descriptors
      obtained for structures optimized for specified solvent using PBE1PBE/6-31G**
      level of theory with the polarizable continuum model. Multiple linear regression,
      M5P, and locally weighted learning techniques were used to achieve accurate
      predictions. The specific quantum chemical descriptors proposed here demonstrated
      high specificity in the majority of the developed models and established direct
      quantitative structure-property relationships.

PMID- 29455383
TI  - Healthcare Experiences of Low-Income Women with Prior Gestational Diabetes.
AB  - Introduction An important yet understudied component of postpartum type 2
      diabetes risk reduction among high risk women is experiences with the healthcare
      system. Our objective was to describe the healthcare experiences of a diverse,
      low-income sample of women with prior GDM, including their suggestions for
      improving care. Methods Focus groups were conducted among African American,
      Hispanic, and Appalachian women who were diagnosed with GDM within the past 10
      years. Participants were recruited from community and medical resources. Twelve
      focus groups were conducted, four within each race-ethnic group. Results Three
      broad themes were identified around barriers to GDM care, management, and follow
      up: (1) communication issues; (2) personal and environmental barriers; and (3)
      type and quality of healthcare. Many women felt communication with their provider
      could be improved, including more education on the severity of GDM, streamlining
      information to be less overwhelming, and providing additional support through
      referrals to community resources. Although women expressed interest in receiving
      more actionable advice for managing GDM during pregnancy and for preventing type
      2 diabetes postpartum, few women reported changing behaviors. Barriers to
      behavior change were related to cost, transportation, and competing demands.
      Several opportunities for improved care were elucidated. Discussion Our findings
      suggest that across all racial and ethnic representations in our sample, low
      income women with GDM experience similar communication, personal, and
      environmental barriers related to the healthcare they receive for their GDM.
      Considering the increased exposure to the health care system during a GDM
      affected pregnancy, there are opportunities to address barriers among women with
      GDM across different race-ethnic groups.

PMID- 29455384
TI  - Novel Interventions to Reduce Stress and Overeating in Overweight Pregnant Women:
      A Feasibility Study.
AB  - Background High stress and depression during pregnancy are risk factors for
      worsened health trajectories for both mother and offspring. This is also true for
      pre-pregnancy obesity and excessive gestational weight gain. Reducing stress and
      depression may be one path to prevent excessive caloric intake and gestational
      weight gain. Study Purpose We tested the feasibility of two novel interventions
      aimed at reducing stress and overeating during pregnancy. Reflecting different
      theoretical underpinnings, the interventions target different mechanisms. Mindful
      Moms Training (MMT) uses mindfulness to improve awareness and acceptance of
      experiences and promote conscious rather than automatic behavior choices.
      Emotional Brain Training (EBT) uses active coping to change perceptions of
      negative experience and promote positive affective states. Methods Forty-six
      overweight/obese low-income women were assigned to either MMT (n = 24) or EBT (n
      = 22) for an 8-week feasibility study. Pre-post changes in perceived stress,
      eating and presumed mechanisms were assessed. Results Women reported high levels
      of stress at baseline. Both interventions were well attended and demonstrated
      clinically significant pre-post reductions in stress, depressive symptoms, and
      improved eating behaviors. MMT significantly decreased experiential avoidance,
      whereas EBT significantly increased positive reappraisal; these changes were
      marginally significantly different by group. Conclusions This feasibility study
      found that both interventions promoted meaningful reductions in stress and
      depressive symptoms and improved reported eating behaviors in a high-risk group
      of pregnant women. Each intervention has a potentially different pathway
      acceptance for MMT and reappraisal for EBT. Larger studies are needed to test
      efficacy on longer term reductions in stress and overeating.

PMID- 29455386
TI  - (Some) current concepts in antibacterial drug discovery.
AB  - The rise of multidrug resistance in bacteria rendering pathogens unresponsive to
      many clinical drugs is widely acknowledged and considered a critical global
      healthcare issue. There is broad consensus that novel antibacterial
      chemotherapeutic options are extremely urgently needed. However, the development
      pipeline of new antibacterial drug lead structures is poorly filled and not
      commensurate with the scale of the problem since the pharmaceutical industry has
      shown reduced interest in antibiotic development in the past decades due to high
      economic risks and low profit expectations. Therefore, academic research
      institutions have a special responsibility in finding novel treatment options for
      the future. In this mini review, we want to provide a broad overview of the
      different approaches and concepts that are currently pursued in this research
      field.

PMID- 29455385
TI  - Transcriptome analysis of wild-type and afsS deletion mutant strains identifies
      synergistic transcriptional regulator of afsS for a high antibiotic-producing
      strain of Streptomyces coelicolor A3(2).
AB  - Most secondary metabolism in Actinobacteria is controlled by multi-layered, gene
      regulatory networks. These regulatory mechanisms are not easily identified due to
      their complexity. As a result, when a strong transcriptional regulator (TR)
      governs activation of biosynthetic pathways of target antibiotics such as
      actinorhodin (ACT), additional enhancement of the biosynthesis is difficult in
      combination with other TRs. To find out any "synergistic transcriptional
      regulators (sTRs)" that show an additive effect on the major, often strong,
      transcriptional regulator (mTR), here, we performed a clustering analysis using
      the transcriptome datasets of an mTR deletion mutant and wild-type strain. In the
      case of ACT biosynthesis in Streptomyces coelicolor, PhoU (SCO4228) and RsfA
      (SCO4677) were selected through the clustering analysis, using AfsS (SCO4425) as
      a model mTR, and experimentally validated their roles as sTRs. Furthermore,
      through analysis of synergistic effects, we were able to suggest a novel
      regulation mechanism and formulate a strategy to maximize the synergistic effect.
      In the case of the double TR mutant strain (DeltarsfA pIBR25::afsS), it was
      confirmed that the increase of cell mass was the major cause of the synergistic
      effect. Therefore, the strategy to increase the cell mass of double mutant was
      further attempted by optimizing the expression of efflux pump, which resulted in
      2-fold increase in the cell mass and 24-fold increase in the production of ACT.
      This result is the highest ACT yield from S. coelicolor ever reported.

PMID- 29455387
TI  - Biochemical process of ureolysis-based microbial CaCO3 precipitation and its
      application in self-healing concrete.
AB  - Urea hydrolysis has already been considered as the most effective pathway for
      microbially induced CaCO3 precipitation (MICP). The present work first studied
      the combination of several key factors including initial pH, temperature, and
      dosage of urea, which contribute to the biochemical process of MICP. Under an
      amiable condition of pH and temperature, the dosage of urea has a significant
      impact on the rate of urea degradation and CaCO3 precipitation. A bacteria-based
      self-healing system was developed by loading healing agents on ceramsite
      carriers. The self-healing efficiency was evaluated by visual inspection on crack
      closure, compressive strength regain, and capillary water absorption. A
      preferable healing effectiveness was obtained when the bacteria and organic
      nutrients were co-immobilized in carriers. Image analysis showed that cracks up
      to 273 MUm could be healed with a crack closure ratio of 86% in 28 days. The
      compressive strength regain increased 24% and the water absorption coefficient
      decreased 27% compared to the reference. The findings indicated a promising
      application of ureolysis-based MICP in restoring the mechanical properties and
      enhancing the durability of concrete.

PMID- 29455388
TI  - Heterologous expression of rTsHyal-1: the first recombinant hyaluronidase of
      scorpion venom produced in Pichia pastoris system.
AB  - In general, hyaluronidases have a broad potential application on medicine and
      esthetics fields. Hyaluronidases from animal venoms cleave hyaluronan present in
      the extracellular matrix, acting as spreading factors of toxins into the tissues
      of the victim. However, the in-depth characterization of hyaluronidase from
      animal venoms has been neglected due to its instability and low concentration in
      the venom, which hamper its isolation. Thus, heterologous expression of
      hyaluronidase acts as a biotechnological tool in the obtainment of enough amounts
      of the enzyme for structural and functional studies. Therefore, this study
      produced a recombinant hyaluronidase from Tityus serrulatus scorpion venom,
      designated as rTsHyal-1, in the Pichia pastoris system. Thus, a gene for TsHyal-1
      (gb|KF623285.1) was synthesized and cloned into the pPICZalphaA vector (GenScript
      Corporation) for heterologous expression in P. pastoris. rTsHyal-1 was expressed
      in laboratorial scale in a buffered minimal medium containing methanol (BMM) for
      96 h with daily addition of methanol. Expression of rTsHyal-1 resulted in a total
      protein yield of 0.266 mg/mL. rTsHyal-1 partially purified through cation
      exchange chromatography presented a specific activity of 1097 TRU/mg, against 838
      TRU/mg for the final expressed material, representing a 1.31-fold purification.
      rTsHyal-1 has molecular mass of 49.5 kDa, and treatment with PNGase F and
      analysis by mass spectrometry (MALDI-TOF) indicated a potential N-glycosylation
      of 4.5 kDa. Additionally, de novo sequencing of rTsHyal-1, performed in MALDI-TOF
      and Q Exactive Orbitrap MS, resulted in 46.8% of protein sequence coverage.
      rTsHyal-1 presents the highest substrate specificity to hyaluronan followed by
      chondroitin-6-sulfate, chondroitin-4-sulfate, and dermatan sulfate and showed an
      optimum activity at pH 6.0 and 40  degrees C. These results validate the
      biotechnological process for the heterologous expression of rTsHyal-1. This is
      the first recombinant hyaluronidase from scorpion venoms expressed in the P.
      pastoris system with preserved enzyme activity.

PMID- 29455389
TI  - Germline mutations of aryl hydrocarbon receptor-interacting protein (AIP) gene
      and somatostatin receptor 1-5 and AIP immunostaining in patients with sporadic
      acromegaly with poor versus good response to somatostatin analogues.
AB  - OBJECTIVE: To determine aryl hydrocarbon interacting protein (AIP) gene
      variations and AIP and somatostatin receptor (SSTR) 1-5 immunostaining in
      patients with apparently sporadic acromegaly with poor versus good response to
      somatostatin analogues (SRLs). METHODS: A total of 94 patients (66 with poor and
      28 with good response to SRLs) were screened for the AIP gene variations using
      Sanger sequencing. Immunostaining was performed in 60 tumors. RESULTS: Several
      variations, albeit some with undetermined significance, were detected, especially
      in poor responder patients. The prevalence of AIP mutation was 2.1% in the whole
      group and 1.5% in patients with poor response to SRLs. AIP, SSTR2A, and SSTR2B
      immunostainings were decreased in patients with poor response (p < 0.05 for all),
      and other SSTRs did not differ between the groups (p > 0.05 for all). Patients
      with low AIP had decreased levels of SSTR2A and SSTR3 (p < 0.05 for all). AIP and
      SSTR2A immunostainings were positively correlated to the treatment response and
      age at diagnosis was negatively correlated (p < 0.05 for all). In poor responder
      patients with high SSTR2A immunostaining, SSTR2B immunostaining and preoperative
      tumor size were positively and negatively correlated, respectively, to SRL
      response (p < 0.05 for all). CONCLUSIONS: Lack of response to SRLs does not
      necessarily increase the risk of harboring AIP mutations. The finding of
      decreased AIP, SSTR2A, and SSTR2B immunostaining in patients with poor response
      to SRLs and decreased SSTR2A and SSTR3 level in those with low AIP immunostaining
      suggests a possible interaction between AIP and some SSTR subtypes that might
      alter SRL sensitivity.

PMID- 29455390
TI  - Utility of multiple rule out CT screening of high-risk atraumatic patients in an
      emergency department-a feasibility study.
AB  - BACKGROUND: Several large trials have evaluated the effect of CT screening based
      on specific symptoms, with varying outcomes. Screening of patients with CT based
      on their prognosis alone has not been examined before. For moderate-to-high risk
      patients presenting in the emergency department (ED), the potential gain from a
      CT scan might outweigh the risk of radiation exposure. We hypothesized that an
      accelerated "multiple rule out" CT screening of moderate-to-high risk patients
      will detect many clinically unrecognized diagnoses that affect change in
      treatment. METHOD: Patients >= 40 years, triaged as high-risk or moderate-to-high
      risk according to vital signs, were eligible for inclusion. Patients were scanned
      with a combined ECG-gated and dual energy CT scan of cerebrum, thorax, and
      abdomen. The impact of the CT scan on patient diagnosis and treatment was
      examined prospectively by an expert panel. RESULTS: A total of 100 patients were
      included in the study, (53% female, mean age 73 years [age range, 43-93]). The
      scan lead to change in treatment or additional examinations in 37 (37%) patients,
      of which 24 (24%) were diagnostically significant, change in acute treatment in
      11 (11%) cases and previously unrecognized malignant tumors in 10 (10%) cases.
      The mean size specific radiation dose was 15.9 mSv (+/- 3.1 mSv). CONCLUSION:
      Screening with a multi-rule out CT scan of high-risk patients in an ED is
      feasible and result in discovery of clinically unrecognized diagnoses and
      malignant tumors, but at the cost of radiation exposure and downstream
      examinations. The clinical impact of these findings should be evaluated in a
      larger randomized cohort.

PMID- 29455391
TI  - Focal Ischaemic Infarcts Expand Faster in Cerebellar Cortex than Cerebral Cortex
      in a Mouse Photothrombotic Stroke Model.
AB  - It is generally accepted that the cerebellum is particularly vulnerable to
      ischaemic injury, and this may contribute to the high mortality arising from
      posterior circulation strokes. However, this has not been systematically examined
      in an animal model. This study compared the development and resolution of matched
      photothrombotic microvascular infarcts in the cerebellar and cerebral cortices in
      adult 129/SvEv mice of both sexes. The photothrombotic lesions were made using
      tail vein injection of Rose Bengal with a 532 nm laser projected onto a 2 mm
      diameter aperture over the target region of the brain (with skull thinning).
      Infarct size was then imaged histologically following 2 h to 30-day survival
      using serial reconstruction of haematoxylin and eosin stained cryosections. This
      was complemented with immunohistochemistry for neuron and glial markers. At 2 h
      post-injury, the cerebellar infarct volume averaged ~ 2.7 times that of the
      cerebral cortex infarcts. Infarct volume reached maximum in the cerebellum in a
      quarter of the time (24 h) taken in the cerebral cortex (4 days). Remodelling
      resolved the infarcts within a month, leaving significantly larger residual
      injury volume in the cerebellum. The death of neurons in the core lesion at 2 h
      was confirmed by NeuN and Calbindin immunofluorescence, alongside activation of
      astrocytes and microglia. The latter persisted in the region within and
      surrounding the residual infarct at 30 days. This comparison of acute focal
      ischaemic injuries in cerebellar and cerebral cortices provides direct
      confirmation of exacerbation of neuropathology and faster kinetics in the
      cerebellum.

PMID- 29455392
TI  - The psychometric evaluation of the quality of life in short stature youth
      (QoLISSY) instrument for German children born small for gestational age.
AB  - PURPOSE: This study aimed to validate the disease-specific "quality of life in
      short stature youth (QoLISSY)-instrument" that assessesQuery the health-related
      quality of life (HrQoL) in German children and adolescents diagnosed as small for
      gestational age (SGA) in a patient and parent report. METHODS: The psychometric
      performance of the German version of the QoLISSY questionnaire was examined in
      terms of reliability and validity in 65 SGA families (17 child reports/64 parent
      reports) and compared to the psychometric performance of the original European
      QoLISSY dataset of over 200 children with growth hormone deficiency and
      idiopathic short stature (ISS). RESULTS: The analysis yielded psychometrically
      favorable results with excellent reliability and acceptable discriminant
      validity. The instrument's operating characteristics were comparable to the
      results of the original European QoLISSY data. In the parent- as well as child
      report, children with SGA had lower HrQoL scores than children with ISS.
      Convergent validity was demonstrated by significant correlations between the
      QoLISSY scales and the generic KIDSCREEN-10 Index. CONCLUSION: Psychometric
      testing suggests that QoLISSY is a promising instrument to assess the HrQoL of
      young German people with SGA. Both versions (parent- and child report) appear to
      detect differences between SGA and other conditions (e.g. ISS). QoLISSY can be
      used in clinical studies, health service research, as well as in practice in
      children with SGA and their parents. For a cross-cultural application of the
      instrument in SGA, the tool needs be validated in sufficiently large SGA samples
      within respective countries.

PMID- 29455393
TI  - Mangiferin inhibits cell migration and invasion through Rac1/WAVE2 signalling in
      breast cancer.
AB  - Breast tumour progression results from the advancement of the disease to a
      metastatic phenotype. Rac1 and Cdc42 belong to the Rho family of genes that,
      together with their downstream effectors, Wiskott-Aldrich Syndrome protein-family
      verprolin-homologous protein 2 (WAVE2) and Arp2/3, assume a vital part in
      cytoskeletal rearrangement and the arrangement of film projections that advance
      malignant cell relocation and invasion. Mangiferin is a characteristic
      polyphenolic compound from Mangifera indica L. (Anacardiaceae), ordinarily
      referred to as mango, that is consumed worldwide as a natural product, including
      culinary and seasoning applications. Mangiferin delays breast malignancy
      development and progression by inhibiting different signalling pathways required
      in mitogenic signalling and metastatic progression. Studies were performed to
      analyse the impact of mangiferin on Rac1/WAVE2 flagging, relocation and invasion
      in highly metastatic human MDA-MB-231 mammary cells. Additional studies led to
      the observation that comparative treatment with mangiferin caused marked
      reduction in tumour cell movement and invasion. Taken together, these discoveries
      demonstrate that mangiferin treatment adequately hinders Rac1/WAVE2 flagging and
      diminishes metastatic phenotypic expression in malignant mammary cells,
      indicating that mangiferin may provide a benefit as a novel restorative approach
      in the treatment of metastatic breast cancer.

PMID- 29455394
TI  - Culture in embryonic kidney serum and xeno-free media as renal cell carcinoma and
      renal cell carcinoma cancer stem cells research model.
AB  - The use of fetal bovine serum hinders obtaining reproducible experimental results
      and should also be removed in hormone and growth factor studies. In particular
      hormones found in FBS act globally on cancer cell physiology and influence
      transcriptome and metabolome. The aim of our study was to develop a renal
      carcinoma serum free culture model optimized for (embryonal) renal cells in order
      to select the best study model for downstream auto-, para- or endocrine research.
      Secondary aim was to verify renal carcinoma stem cell culture for this
      application. In the study, we have cultured renal cell carcinoma primary tumour
      cell line (786-0) as well as human kidney cancer stem cells in standard 2D
      monolayer cultures in Roswell Park Memorial Institute Medium or Dulbecco's
      Modified Eagle's Medium and Complete Human Kidney Cancer Stem Cell Medium,
      respectively. Serum-free, animal-component free Human Embryonic Kidney 293 media
      were tested. Our results revealed that xeno-free embryonal renal cells optimized
      culture media provide a useful tool in RCC cancer biology research and at the
      same time enable effective growth of RCC. We propose bio-mimic RCC cell culture
      model with specific serum-free and xeno-free medium that promote RCC cell
      viability.

PMID- 29455395
TI  - Anti-cancer effect of Aquaporin 5 silencing in colorectal cancer cells in
      association with inhibition of Wnt/beta-catenin pathway.
AB  - Aquaporin 5 (AQP5) is a water channel protein that is over-expressed in many
      tumors. Elevated expression of AQP5 is associated with poor prognosis of
      colorectal cancer. Yet, whether AQP5 plays a role in epithelial-mesenchymal
      transition (EMT) of colorectal cancer has not been reported until now. Here we
      aim to investigate the function of AQP5 in the EMT process of colorectal cancer.
      We transfected HCT116 and SW480 cells with AQP5-specific shRNA and verified the
      knockdown efficiency through western blotting and real-time PCR. Afterwards,
      scratch wound healing assay, invasion assay, gelatin zymography,
      immunofluorescence staining and immunoblotting were performed to assess the
      effect of AQP5 silencing in these two cells. The ability of migration and
      invasion of colorectal cancer cells was significantly impaired after AQP5
      silencing. Correspondingly, the activity and expression of Matrix
      Metallopeptidase (MMP)-2 and MMP-9 were reduced. Moreover, the expression levels
      of EMT-related factors were altered: E-cadherin, Tissue Inhibitor Of
      Metalloproteinases (TIMP)-1 and TIMP-2 were upregulated, whereas Vimentin, N
      cadherin, Plasminogen Activator, Urokinase (uPA) and Snail were downregulated
      following knockdown of AQP5 in colorectal cancer cells. Furthermore, the
      expression of Wnt1 and beta-catenin was markedly decreased after AQP5 knockdown.
      Interestingly, the alteration of EMT-related factors mediated by AQP5 knockdown
      could be reversed by upregulation of beta-catenin. Taken together, silencing of
      AQP5 restrained the migration and invasion of colorectal cancer cells, and
      regulated the expression of EMT-related molecules in them by inhibiting Wnt/beta
      catenin pathway.

PMID- 29455396
TI  - Reversible cerebral vasoconstriction syndrome accompanied by hypomagnesemia.

PMID- 29455397
TI  - Interarm skin temperature differences: manifestation of subclavian steal
      syndrome?

PMID- 29455398
TI  - MR imaging of neoplastic and non-neoplastic lesions of the brain and spine in
      neurofibromatosis type I.
AB  - The aim of this work is to review the MR imaging of neoplastic and non-neoplastic
      lesions of the brain and spine in neurofibromatosis type I. Neoplastic lesions
      are optic pathway gliomas, brain stem gliomas, other gliomas of the brain, and
      peripheral nerve sheath tumors. Structural changes in the brain include
      unidentified bright objects, macrocephaly, and enlarged corpus callosum. Bony
      dysplasia changes as sphenoid ridge dysplasia, spinal scalloping, dural ectasia,
      and meningoceles. Vasculopathy and cortical cerebral and cerebellar malformations
      of the brain have been reported.

PMID- 29455399
TI  - Human figure drawing distinguishes Alzheimer's patients: a cognitive screening
      test study.
AB  - To study human figure drawing in a group of Alzheimer's disease (AD) patients and
      compare it with a group of patients with mild cognitive impairment (MCI) and
      controls. We evaluated consecutive outpatients over a one-year period. Patients
      were classified as affected by AD or by MCI. All patients and controls underwent
      a simplified version of the human-figure drawing test and MMSE. A qualitative and
      quantitative analysis of all human figures was obtained. 112 AD, 100 MCI patients
      and 104 controls were enrolled. AD patients drew human figures poor in details
      and globally smaller than MCI patients and controls. Human figures drawn by MCI
      patients are intermediate in body height between those of the AD patients and the
      healthy subjects. The head-to-body ratio of human figures drawn by AD patients is
      greater than controls and MCI patients, while the human figure size-relative-to
      page space index is significantly smaller. Body height is an independent
      predictor of cognitive impairment correlating with its severity and with the
      number of the figure's details. Human figures drawn by AD patients are different
      from those drawn by healthy subjects and MCI patients. Human figure drawing test
      is a useful tool for orienting cognitive impairment's diagnosis.

PMID- 29455400
TI  - Cerebral arteriovenous malformation presenting as isolated bilateral pupil
      sparing oculomotor, pseudoabducens palsy, and hemiataxia.

PMID- 29455401
TI  - New clinical characteristics and risk factors of hand knob infarction.
AB  - Hand knob infarction (HKI) is a rare clinical condition which is often
      misdiagnosed as peripheral neuropathy. This study aimed to identify the clinical
      characteristics and risk factors of HKI. Nine HKI patients admitted between
      January 2013 and March 2016 were confirmed by magnetic resonance imaging. Their
      medical records were collected and analyzed. The modified Rankin Scale was used
      to assess clinical outcomes. Routine laboratory tests, electrocardiogram,
      echocardiography, cranial magnetic resonance imaging, magnetic resonance
      angiography, computed tomography angiography, and Doppler ultrasonography
      examinations were performed. Seven patients had uniform involvement of all
      digits. One patient with radial weakness had a lesion in the lateral area of hand
      knob, and another patient with ulnar weakness had a lesion distributed in the
      medial area of hand knob. Hyperhomocysteinemia was a most common risk factor for
      HKI. Most HKI patients had a benign disease course, but three patients (33.33%)
      with the stroke type of large artery atherosclerosis had disease recurrence. We
      characterized clinical characteristics and risk factors of HKI which will help
      the diagnosis and management of HKI.

PMID- 29455402
TI  - Pharyngeal-cervical-brachial variant of Guillain-Barre syndrome with predominant
      bulbar palsy and anti-GM3 IgG antibodies.

PMID- 29455403
TI  - Aseptic central nervous system infections in adults: what predictor for unknown
      etiological diagnosis?
AB  - Despite the availability of nucleic acid amplification tests (NAATs), most of
      aseptic acute meningitides, encephalitides, and meningoencephalitides (AAMEMs) in
      adults remain of unknown etiology so far. To shed light on such topic, we aimed
      to evaluate potential predictors for AAMEMs of unknown origin. We collected
      retrospectively data from all consecutive cases of AAMEMs in adults discharged
      from an Italian referral hospital, from January 2004 to December 2016. Laboratory
      analysis included common immunometric methods and NAATs. Potential predictors for
      unknown etiology (age, seasonality, serum C-reactive protein value, antibiotic
      use before lumbar puncture, immunodeficiency conditions, clinical symptoms and
      signs) were evaluated by a logistic regression analysis model. A p value <= 0.05
      was considered to indicate statistical significance. The study included 92
      patients (median age 39 years; 54.3% males) affected by meningitis (n = 57),
      encephalitis (n = 25), and meningoencephalitis (n = 10). The identified agents
      that cause AAMEMs were herpesviruses (20.7%), enteroviruses (5.4%), tick-borne
      encephalitis virus (3.3%), influenza virus A (2.2%), West Nile virus (1.1%), and
      parvovirus B19 (1.1%), while 66.3% of cases were of unknown etiology. No
      predictor was found to be significantly associated with AAMEMs of unknown
      etiology. We suggest that potential infectious agents causing undiagnosed cases
      should be investigated among non-bacterial, non-opportunistic, and non-seasonal
      organisms.

PMID- 29455404
TI  - The Effect of Pre-Surgery Information Online Lecture on Nutrition Knowledge and
      Anxiety Among Bariatric Surgery Candidates.
AB  - INTRODUCTION: Best practices for patient education in bariatric surgery (BS)
      remain undefined. The aims of this study were to evaluate the effect of an online
      lecture on nutrition knowledge, weight loss expectations, and anxiety among BS
      candidates and present a new tool to assess this knowledge before BS. METHODS: An
      interventional non-randomized controlled trial on 200 BS candidates recruited
      while attending a pre-BS committee. The first 100 consecutive patients were
      assigned to the control group and the latter 100 consecutive patients to the
      intervention group and were instructed to watch an online lecture of 15-min 1-2
      weeks prior to surgery. All participants completed a BS nutrition knowledge and
      the state-trait anxiety inventory (STAI) questionnaires at the pre-BS committee
      and once again at the pre-surgery clinic. Body mass index (BMI), comorbidities,
      surgery type, marital status, and number of dietitian sessions were obtained from
      medical records. RESULTS: Data for paired study questionnaires scores were
      available for 128 patients (n = 69 and n = 59 for the control and intervention
      groups, respectively), with a mean age and BMI of 40.3 +/- 11.4 years and 41.3 +/
      4.9 kg/m2, respectively. The BS nutrition knowledge and the state anxiety scores
      increased for both study groups at the pre-surgery clinic as compared to the pre
      BS committee (P <= 0.028), but the improvement in the nutrition knowledge score
      was significantly higher for the intervention group (P = 0.030). No within or
      between-group differences were found for the trait anxiety items score. The
      "dream" and "realistic" weight goals were lower than the expected weight loss
      according to 70% excess weight loss (EWL) for both study groups at both time
      points (P < 0.001 for all). CONCLUSION: Education by an online lecture prior to
      the surgery improves BS nutrition knowledge, but not anxiety. ClinicalTrials.gov
      number: NCT02857647.

PMID- 29455405
TI  - Bariatric Surgery in Patients on Chronic Anticoagulation Therapy.
AB  - BACKGROUND: Perioperative management of chronically anti-coagulated patients
      undergoing bariatric surgery requires a balance of managing hemorrhagic and
      thromboembolic risks. The aim of this study is to evaluate the incidence of
      hemorrhagic complications and their management in chronically anticoagulated
      (CAT) patients undergoing bariatric surgery. METHODS: A retrospective review of
      CAT patients undergoing bariatric surgery at an academic center from 2008 to 2015
      was studied. RESULTS: A total of 153 patients on CAT underwent surgery [Roux-en-Y
      gastric bypass (n = 79), sleeve gastrectomy (n = 63), and adjustable gastric
      banding (n = 11)] during the study period: 85 patients (55%) were females; median
      age was 56 years (interquartile range [IQR] 49-64), and median BMI was 49 kg/m2
      (IQR 43-56). The most common indications for CAT were venous thromboembolism (n =
      87) and atrial fibrillation (n = 83). Median duration of procedure and estimated
      intraoperative blood loss was 150 min (IQR 118-177) and 50 ml (IQR 25-75),
      respectively. Thirty-day postoperative complications were reported in 33 patients
      (21.6%) including postoperative bleeding (n = 19), anastomotic leak (n = 3), and
      pulmonary embolism (n = 1). Nineteen patients (12%) with early postoperative
      bleeding were further categorized to intra-abdominal (n = 10), intraluminal (n =
      6), and at the port site or abdominal wall (n = 3). All-cause readmissions within
      30 days of surgery occurred in 19 patients (12%). There was no 30-day mortality.
      CONCLUSION: In our experience, patients who require chronic anticoagulation
      medication are higher than average risk for postoperative complications and all
      cause readmission rates. Careful surgical technique and close attention to
      postoperative anticoagulation protocols are essential to decrease perioperative
      risk in this high-risk cohort.

PMID- 29455406
TI  - Conversional Weight Loss Surgery: an Australian Experience of Converting
      Laparoscopic Adjustable Gastric Bands to Laparoscopic Sleeve Gastrectomy.
AB  - BACKGROUND: Bariatric surgery is the most effective treatment for severe obesity,
      capable of producing more than 50% excess weight loss at 10-year follow-up (James
      Clin Dermatol 1; 22:276-80; O'Brien Br J Surg 2; 102:611-17; Buchwald et al.
      Metab Syndr 3; 347-56). The success of bariatric surgery extends far beyond
      weight loss, with up to 80-90% of patients having improvement or resolution of
      many of their weight-related co-morbidities including type II diabetes mellitus
      and hypertension (Puzziferri et al. JAMA 4; 312:934-42; Buchwald et al. Am J Med
      5; 122:248-56). However, there is a paucity of data regarding conversional
      bariatric surgery. OBJECTIVE: This study aims to explore the efficacy, safety and
      feasibility of conversional surgery. SETTING: This study represents the largest
      Australasian series focusing on conversional bariatric surgery. The study was
      conducted in the Norwest Private Hospital and Hospital for Specialist Surgery
      (HSS), both private Hospitals in Sydney, Australia. METHODS: Data was collected
      prospectively at regular intervals for more than 12 months from 1 January 2012 to
      1st November 2015 for all patients requiring a laparoscopic sleeve gastrectomy
      (LSG) as secondary procedure after prior laparoscopic adjustable gastric band
      (LAGB). Excess weight loss (EWL), percentage total body weight loss (TWL) and
      excess BMI loss (EBMIL) as well as any complications were recorded. RESULTS:
      There were low rates of morbidity (1.1%) and no mortality at 12-month follow-up.
      Satisfactory EWL of 60% (95% CI: 56.6-63.4%), EBMIL of 60.1% (95% CI: 48.8-71.4%)
      and 16% TWL was achieved at 12-month follow-up. CONCLUSION: We therefore conclude
      that sleeve gastrectomy is a safe and valid option for conversional bariatric
      surgery following LAGB.

PMID- 29455407
TI  - A Single-center Experience Examining the Length of Stay and Safety of Early
      Discharge After Laparoscopic Roux-en-Y Gastric Bypass Surgery.
AB  - PURPOSE: This study's objective was to describe our experience and evaluate the
      safety of early discharge (ED) following laparoscopic Roux-en-Y gastric bypass
      (LRYGB) in a specific patient population. MATERIALS AND METHODS: Patients
      undergoing LRYGB at Montefiore Medical Center were retrospectively reviewed.
      Patients readmitted in the first 30 days following surgery were compared to those
      patients who were not readmitted. Data analysis was used to compare groups and to
      determine factors associated with readmission. In addition to patient
      demographics, length of stay (LOS) was analyzed as an independent risk factor for
      readmission. RESULTS: A total of 630 LRYGB were performed during this period.
      There were 5.1% (n = 32) of patients that required readmission within 30 days of
      discharge. Readmitted patients had a higher BMI (50.0 vs. 45.8; p = 0.006) and
      there was a trend for them to be younger (38.4 years vs. 42.0; p = 0.07). There
      was an increased rate of ED in 2015 (36.7%, n = 121) compared to 2014 (29.9%, n =
      90). The readmission rate for ED for the study period was 4.7% (n = 10). There
      were no observed mortalities in our early discharge group of patients.
      CONCLUSIONS: Discharge on post-operative day 1 following a LRYGB is safe and is
      not associated with an increased likelihood of being readmitted within 30 days of
      discharge. Our single-center experience helps to better characterize current
      patient profiles and length of stay trends within the field and can be used to
      establish a randomized controlled trial for discharging patients early after
      LRYGB.

PMID- 29455408
TI  - Frequency and treatment of hydrocephalus prior to and after posterior fossa tumor
      surgery in adult patients.
AB  - BACKGROUND: There is paucity of information about the frequency of hydrocephalus
      prior to and after posterior fossa tumor surgery in adult patients and about the
      best way it should be managed. The present study was conducted to determine the
      frequency of hydrocephalus prior to and after posterior fossa tumor surgery in
      adult patients as well as the value of an endoscopic third ventriculostomy (ETV)
      prior to posterior fossa tumor surgery with regard to the rate of perioperative
      complications and persistent hydrocephalus. METHODS: A single-institution
      retrospective chart review of all posterior fossa tumor surgeries of our
      department in a 10-year period (2005 to 2014) has been done. RESULTS: Fifty-two
      of 243 adult patients with posterior fossa tumors presented with hydrocephalus at
      the time of admission prior to tumor surgery. 39/52 received early tumor surgery,
      11/52 an ETV prior to tumor surgery and in 2/52 an external ventricular drainage
      (EVD) was inserted prior to tumor surgery. 3/52 patients required a permanent
      cerebrospinal fluid (CSF) diverting procedure for persistent hydrocephalus after
      tumor removal. One hundred ninety-one patients did not demonstrate a
      hydrocephalus before surgical treatment and four of them developed a post
      resection hydrocephalus. CONCLUSION: The frequency of hydrocephalus prior to
      posterior fossa tumor surgery in adult patients is 21.4% and therefore much lower
      than in respective reports of pediatric patients. The risk of persistent
      hydrocephalus and newly developed hydrocephalus after tumor surgery was very low,
      too (5.7 and 2.1%, respectively). An ETV is not justified in every adult patient
      prior to posterior fossa tumor surgery.

PMID- 29455409
TI  - How I do it: endoscopic endonasal approach to the inferior third of the clivus.
AB  - BACKGROUND: Nowadays, endoscopic endonasal expanded approach targeting for the
      clival lower third is well described in literature. Nonetheless, great variations
      can be found among surgical groups, specially during the earlier stages of this
      procedure. METHOD: We present a step by step description of the clival lower
      third approach until entering the dural space, setting its bony limits. We
      describe the basipharyngeal flap tailoring as a helpful option for latter
      reconstruction. The study of cadaveric specimens adds clarifying dissections.
      CONCLUSIONS: The expansion in the coronal plane is providential in most of the
      intradural lesions of the inferior clivus. Basipharyngeal flap may help seal the
      surgical defects in this area.

PMID- 29455410
TI  - Can patients with symptomatic Tarlov cysts be differentiated from patients with
      specific low back pain based on comprehensive history taking?
AB  - BACKGROUND: Tarlov cysts (TCs) are expanded nerve root sheaths that occur near
      the dorsal root ganglion and result from increased intraspinal hydrostatic
      pressure. TCs most frequently affect the lumbosacral plexus and therefore may
      cause specific symptoms such as perineal pain and neurogenic bladder, bowel, and
      sphincter problems. It has been estimated that 1% of the population has
      symptomatic Tarlov cysts (STCs). However, STCs appear to be underdiagnosed, with
      the pain reported by patients commonly attributed to degenerative alterations
      seen on MRI. The aim of the present study is to investigate the utility of a
      comprehensive questionnaire for use by physicians in establishing the diagnosis
      of STCs. METHODS: We compared questionnaire responses regarding patient history
      between 33 patients diagnosed with symptomatic TCs and 42 patients with chronic
      low back pain and sciatica due to disc problems or degenerative or inflammatory
      disorders. The diagnosis of STCs was confirmed using nerve conduction studies
      (NCS) and electromyography (EMG) of the sacral myotomes by an expert
      neurophysiologist. RESULTS: The questionnaire responses revealed specific
      differences in perineal symptoms (perineal pain, dyspareunia, coccygodynia),
      bowel symptoms (constipation, diarrhea), bladder symptoms (hesitation, retention,
      frequency), and anal sphincter problems (anal pain, mild fecal incontinence).
      Additionally, sitting, walking, and straining aggravated pain more frequently in
      STC patients, and STC patients were more often forced to stop working and/or
      reduce their social activities. CONCLUSIONS: Including the above-listed items in
      the patient history might facilitate differentiation of low back pain and
      sciatica due to STCs from that due to disc problems or degenerative or
      inflammatory disorders.

PMID- 29455411
TI  - Completion of Gamma Knife radiosurgery for AVM treatment after unplanned
      interruption-technical note.
AB  - BACKGROUND AND IMPORTANCE: Gamma Knife radiosurgery is an established technique
      for non-urgent treatment of various intracranial pathologies. Intra-procedural
      dislodgement of the stereotactic frame is an uncommon occurrence that could lead
      to abortion of ongoing treatment and necessitate more invasive treatment
      strategies. CLINICAL PRESENTATION: In this case report, we describe a novel
      method for resumption of Gamma Knife treatment after an unplanned intra
      procedural interruption. The case example involves a radiosurgical treatment of a
      Spetzler-Martin grade I arteriovenous malformation. CONCLUSION: Our technique
      involves integration of scans and coordinate systems from two imaging sessions
      using the composite isodose line to resolve translational differences, thereby
      limiting delivery of remaining shots to the untreated region of the lesion. MRI
      follow-up at 13 months showed a reduction in the nidus size with no evidence of
      any radiation injury to the surrounding brain parenchyma. We believe this
      technique will allow care teams to effectively salvage interrupted Gamma Knife
      procedures and reduce progression to more invasive treatment options.

PMID- 29455413
TI  - Influence of ABO blood type on the outcome after non-aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND: In patients with non-aneurysmal subarachnoid hemorrhage (NA-SAH), the
      etiology is unknown and the bleeding source remains unidentified. However, the
      ABO blood type system has a profound role in patient's hemostasis and thrombosis.
      To date, the aspect of ABO blood type in incidence, clinical course, and outcome
      after NA-SAH has not been investigated. METHODS: In this retrospective analysis,
      81 patients with non-traumatic and non-aneurysmal subarachnoid hemorrhage treated
      between 2010 and 2014 at the author's institution were included. WFNS admission
      status, cerebral vasospasm, delayed infarction, ventriculoperitoneal shunt
      necessity, the Fisher grade, and the modified Rankin Scale were analyzed for
      their association with ABO blood type. Four hundred seventy patients with
      aneurysmal subarachnoid hemorrhage served as a control group. RESULTS: The AB
      blood type is more frequent in NA-SAH compared to aneurysmal patients and the
      German population (OR 2.45, p <= 0.05). Furthermore, NA-SAH with AB blood type
      showed a similar sequelae compared to aneurysmal patients in terms of shunt
      necessity (OR 2.00, p >= 0.05), cerebral vasospasm (OR 1.66, p >= 0.05), and
      delayed infarctions (OR 1.07, p >= 0.05). CONCLUSION: The clinical course of NA
      SAH AB blood type patients shows similar severity as of aneurysmal subarachnoid
      hemorrhage. Therefore, patients with AB blood type should be under intensified
      observation.

PMID- 29455415
TI  - "Defense" type wounds in suicide.
AB  - "Defense" type wounds are sustained when a victim is attempting to ward off an
      attacker, or a weapon. A 39-year-old woman is reported who was found deceased
      with incised wounds to the dorsa of both hands that resembled defense wounds.
      Examination of the flexor surfaces of both wrists, however, revealed horizontal
      incised wounds typical of self-infliction. Perfusion of the subclavian arteries
      produced leakage of water from peripheral veins within wounds on both hands and
      the right wrist. Death was due to exsanguination from incised wounds of the hands
      and right wrist; manner suicide. This case demonstrates the difficulties that may
      arise in differentiating self-inflicted from assaultive wounds. On occasion
      suicidal sharp force injuries may be multiple and in atypical locations. In these
      circumstances a high index of suspicion for homicide must be maintained.

PMID- 29455414
TI  - Defining G protein-coupled receptor peptide ligand expressomes and signalomes in
      human and mouse islets.
AB  - INTRODUCTION: Islets synthesise and secrete numerous peptides, some of which are
      known to be important regulators of islet function and glucose homeostasis. In
      this study, we quantified mRNAs encoding all peptide ligands of islet G protein
      coupled receptors (GPCRs) in isolated human and mouse islets and carried out in
      vitro islet hormone secretion studies to provide functional confirmation for the
      species-specific role of peptide YY (PYY) in mouse islets. MATERIALS AND METHODS:
      GPCR peptide ligand mRNAs in human and mouse islets were quantified by
      quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP
      and TFRC. The pathways connecting GPCR peptide ligands with their receptors were
      identified by manual searches in the PubMed, IUPHAR and Ingenuity databases.
      Distribution of PYY protein in mouse and human islets was determined by
      immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets
      was measured by radioimmunoassay. RESULTS: We have quantified GPCR peptide ligand
      mRNA expression in human and mouse islets and created specific signalomes mapping
      the pathways by which islet peptide ligands regulate human and mouse GPCR
      signalling. We also identified species-specific islet expression of several GPCR
      ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than
      human islets, suggesting a more important role of locally secreted Pyy in mouse
      islets. This was confirmed by IHC and functional experiments measuring insulin,
      glucagon and somatostatin secretion. DISCUSSION: The detailed human and mouse
      islet GPCR peptide ligand atlases will allow accurate translation of mouse islet
      functional studies for the identification of GPCR/peptide signalling pathways
      relevant for human physiology, which may lead to novel treatment modalities of
      diabetes and metabolic disease.

PMID- 29455416
TI  - Pharmacological Inhibition of the Skeletal IKKbeta Reduces Breast Cancer-Induced
      Osteolysis.
AB  - IKKbeta has previously been implicated in breast cancer bone metastasis and bone
      remodelling. However, the contribution of IKKbeta expressed by bone cells of the
      tumour microenvironment to breast cancer-induced osteolysis has yet to be
      investigated. Here, we studied the effects of the verified selective IKKbeta
      inhibitors IKKbetaIII or IKKbetaV on osteoclast formation and osteoblast
      differentiation in vitro and in vivo, human and mouse breast cancer cells'
      support for osteoclast formation and signalling in vitro and osteolysis ex vivo
      and in immunocompetent mice after supracalvarial injection of human MDA-MB-231
      conditioned medium or intra-cardiac injection of syngeneic 4T1 breast cancer
      cells. Pre-treatment with IKKbetaIII or IKKbetaV prior to exposure to tumour
      derived factors from human and mouse breast cancer cell lines protected against
      breast cancer-induced osteolysis in two independent immunocompetent mouse models
      of osteolysis and the ex vivo calvarial bone organ system. Detailed functional
      and mechanistic studies showed that direct inhibition of IKKbeta kinase activity
      in osteoblasts and osteoclasts was associated with significant reduction of
      osteoclast formation, enhanced osteoclast apoptosis and reduced the ability of
      osteoblasts to support osteoclastogenesis in vitro. When combined with previous
      findings that suggest NFkappaB inhibition reduces breast cancer tumorigenesis and
      metastasis our present findings have an important clinical implication on raising
      the possibility that IKKbeta inhibitors, as bone anabolics, osteoclast inhibitors
      as well as anti-metastatic agents, may have advantages over anti-osteoclasts
      agents in the treatment of both skeletal and non-skeletal complications
      associated with metastatic breast cancer.

PMID- 29455418
TI  - Preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for
      locally advanced esophageal carcinosarcoma: a case report and review of the
      literature.
AB  - BACKGROUND: Esophageal carcinosarcoma is a relatively rare malignant neoplasm
      composed of both epithelial carcinomatous and mesenchymal sarcomatous elements.
      There is no recommended clinical treatment for esophageal carcinosarcoma because
      of the rarity of the disease. This report describes a case of esophageal
      carcinosarcoma that was effectively treated with docetaxel, cisplatin, and 5
      fluorouracil as preoperative chemotherapy. CASE PRESENTATION: A 73-year-old man
      had a chief complaint of dysphagia with epigastric pain.
      Esophagogastroduodenoscopy (EGD) revealed a polypoid neoplasm combined with an
      infiltrative ulcer that exhibited a mixture of squamous cell carcinoma and
      spindle cell sarcoma histologically. Computed tomography findings showed swollen
      lymph nodes in the mediastinum and around the cardia. We diagnosed esophageal
      carcinosarcoma cT3N1M0 cStage III. After preoperative chemotherapy with
      docetaxel, cisplatin, and 5-fluorouracil, the patient underwent thoracoscopic
      esophagectomy with three-field lymph node dissection. Histological findings
      revealed that the sarcomatous component had completely disappeared and the
      carcinomatous component was only confined by the basement membrane with scar
      formation of the muscularis propria. Mural fibrotic lesions were observed in
      several resected regional lymph nodes. Hence, immediately after preoperative
      therapy, the esophageal carcinosarcoma was diagnosed as ypTisN0M0 fStage I. The
      patient remained alive without tumor recurrence at 12 months after the operation.
      CONCLUSIONS: A review of the literature revealed that there is still no
      established therapeutic strategy for locally advanced esophageal carcinosarcoma,
      especially against the sarcomatous component. We herein provide the first report
      in which the sarcomatous component showed a complete response to preoperative
      chemotherapy with docetaxel, cisplatin, and 5-fluorouracil. Preoperative
      chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by
      esophagectomy with extended lymphadenectomy may achieve definitive treatment for
      locally advanced esophageal carcinosarcoma.

PMID- 29455417
TI  - Effect of Yulangsan Polysaccharide on the Reinstatement of Morphine-Induced
      Conditioned Place Preference in Sprague-Dawley Rats.
AB  - We previously reported that Yulangsan polysaccharide (YLSP), which was isolated
      from the root of Millettia pulchra Kurz, attenuates withdrawal symptoms of
      morphine dependence by regulating the nitric oxide pathway and modulating
      monoaminergic neurotransmitters. In this study, we investigated the effects and
      mechanism of YLSP on the reinstatement of morphine-induced conditioned place
      preference (CPP) in rats. A CPP procedure was employed to assess the behavior of
      rats, and indicators of serum and four brain regions (nucleus accumbens, ventral
      tegmental area, hippocampus and prefrontal cortex) were determined to explore its
      underlying mechanism. YLSP inhibited priming morphine-induced reinstatement of
      CPP in a dose-dependent manner. YLSP markedly reduced nitric oxide and nitric
      oxide synthase levels in the brain. Moreover, YLSP significantly decreased the
      dopamine and norepinephrine levels in the serum and brain. Furthermore, YLSP
      significantly decreased cyclic adenosine monophosphate (cAMP) and cyclic
      guanosine monophosphate (cGMP) concentrations, inhibited the expression of
      dopamine D1 receptors and cAMP response element binding protein mRNA, and
      improved the expression of dopamine D2 receptor mRNA in the four brain regions.
      Our findings indicated that YLSP could inhibit the reinstatement of morphine
      induced CPP possibly by modulating the NO-cGMP and D1R-cAMP signaling pathways.

PMID- 29455419
TI  - Further aspects of Toxoplasma gondii elimination in the presence of metals.
AB  - Toxoplasma gondii, the etiological agent of toxoplasmosis, infects nucleated
      cells and then resides and multiplies within a parasitophorous vacuole. For this
      purpose, the parasite secretes many virulence factors for the purpose of invading
      and subverting the host microbicidal defenses in order to facilitate its survival
      in the intracellular milieu. Essential metals are structural components of
      proteins and enzymes or cofactors of enzymatic reactions responsible for these
      parasitic survival mechanisms. However, an excess of non-essential or essential
      metals can lead to parasite death. Thus, infected host cells were incubated with
      20 MUM ZnCl2 in conjunction with 3 MUM CdCl2 or HgCl2 for 12 h in order to
      investigate cellular events and organelle damage related to intracellular
      parasite death and elimination. In the presence of these metals, the tachyzoites
      undergo lipid uptake and transport impairment, functional and structural
      mitochondrial disorders, DNA condensation, and acidification of the
      parasitophorous vacuole, thus leading to parasite death. Additional research has
      suggested that lysosome-vacuole fusion was involved in parasite elimination since
      acid phosphatases were found inside the parasitophorous vacuole, and vacuoles
      containing parasites were also positive for autophagy. In conclusion, low
      concentrations of CdCl2, HgCl2, and ZnCl2 can cause damage to Toxoplasma gondii
      organelles, leading to loss of viability, organelle death, and elimination
      without causing toxic effects to host cells.

PMID- 29455420
TI  - Molecular characterization of Hepatozoon canis from farm dogs in Pakistan.
AB  - Hepatozoon canis is a tick-borne pathogen of canids, which is distributed
      worldwide. However, very little is known about this protozoan parasite in
      Pakistan. This study provides the first molecular evidence of H. canis from farm
      dogs from three agro-ecological zones of Punjab, Pakistan. A conventional PCR
      targeting the 18S rRNA gene was used to characterize H. canis from farm dogs from
      three districts, namely Kasur, Rawalpindi, and Muzaffargarh, in Punjab. Of 341
      blood samples tested, 155 (45.5%) were positive for H. canis, 73 (61.3%) from
      Kasur, 46 (42.5%) from Rawalpindi, and 36 (31.5%) from Muzaffargarh. Phylogenetic
      analyses revealed that 18S rRNA sequences of H. canis from this study clustered
      in three clades with those of H. canis from previously published studies to the
      exclusion of all other Hepatozoon spp. included in the analysis. This study
      provides the first insight into H. canis from farm dogs in Pakistan. Furthermore,
      it lays a foundation for future studies of the parasite to assess the impact of
      canine hepatozoonosis in dogs from various agro-ecological zones in Pakistan
      where pet ownership of dogs is increasing.

PMID- 29455422
TI  - Correction to: Learning curves of two different techniques for the intra
      articular injection of the knee joint under fluoroscopic guidance.
AB  - The published version of this article contained a mistake. In Table 1 of the
      original article, the numbers of successful injections and failed injections were
      not correct. The correct Table 1 should read as given below.

PMID- 29455421
TI  - Impact of baseline characteristics on outcomes of advanced HCC patients treated
      with sorafenib: a secondary analysis of a phase III study.
AB  - BACKGROUND: The current study aims to investigate the impact of baseline
      characteristics on the outcomes of sorafenib-treated advanced Hepatocellular
      carcinoma (HCC) patients in the setting of a clinical trial. METHODS: This is a
      secondary analysis of the comparator arm (sorafenib arm) of the NCT00699374 study
      which is a phase III multicenter study conducted between 2008 and 2010. The
      univariate probability of overall and progression-free survival was assessed
      among different patient subsets through Kaplan-Meier analysis and log-rank
      testing. Multivariate analysis of factors affecting overall and progression-free
      survival was then conducted through Cox regression analysis. RESULTS: All
      patients within the comparator (sorafenib) arm were included in the analysis (N =
      544 patients). In multivariate analysis, prior hepatectomy (P = 0.028), prior
      locoregional treatment (P = 0.048), grade 1 ALBI score (P < 0.001), ECOG
      performance score of 0 (P < 0.001), BMI >= 25 (P = 0.026), AFP < 200 (P = 0.001),
      and no extra-hepatic spread (P = 0.007) were associated with better overall
      survival. Likewise, in multivariate analysis, non-Asian race (P = 0.004), grade 1
      ALBI score (P = 0.001), ECOG performance score of 0 (P = 0.006), and no extra
      hepatic spread (P = 0.005) were associated with better progression-free survival.
      Moreover, development of high-grade hand-foot skin reaction was associated with a
      statistically significant improvement in overall survival (P = 0.003), which was
      further confirmed in a multivariate analysis adjusted for other relevant baseline
      factors (P = 0.002). CONCLUSION: Within a cohort of highly selected advanced HCC
      patients, baseline patient-, liver-, and disease-centered variables play an
      important role in predicting patient outcomes. This information is important in
      terms of therapeutic decision-making and patient counseling.

PMID- 29455423
TI  - Assessment of cerebral microbleeds by susceptibility-weighted imaging at 3T in
      patients with end-stage organ failure.
AB  - PURPOSE: Cerebral microbleeds (CMBs) are small rounded lesions representing
      cerebral hemosiderin deposits surrounded by macrophages that results from
      previous microhemorrhages. The aim of this study was to review the distribution
      of cerebral microbleeds in patients with end-stage organ failure and their
      association with specific end-stage organ failure risk factors. MATERIALS AND
      METHODS: Between August 2015 and June 2017, we evaluated 15 patients, 9 males,
      and 6 females, (mean age 65.5 years). Patients population was subdivided into
      three groups according to the organ failure: (a) chronic kidney failure (n = 8),
      (b) restrictive cardiomyopathy undergoing heart transplantation (n = 1), and (c)
      end-stage liver failure undergoing liver transplantation (n = 6). The MR exams
      were performed on a 3T MR unit and the SWI sequence was used for the detection of
      CMBs. CMBs were subdivided in supratentorial lobar distributed, supratentorial
      non-lobar distributed, and infratentorial distributed. RESULTS: A total of 91
      microbleeds were observed in 15 patients. Fifty-nine CMBs lesions (64.8%) had
      supratentorial lobar distribution, 17 CMBs lesions (18.8%) had supratentorial non
      lobar distribution and the remaining 15 CMBs lesions (16.4%) were infratentorial
      distributed. An overall predominance of supratentorial multiple lobar
      localizations was found in all types of end-stage organ failure. The presence of
      CMBs was significantly correlated with age, hypertension, and specific end-stage
      organ failure risk factors (p < 0.001). CONCLUSIONS: CMBs are mostly founded in
      supratentorial lobar localization in end-stage organ failure. The improved
      detection of CMBs with SWI sequences may contribute to a more accurate
      identification of patients with cerebral risk factors to prevent complications
      during or after the organ transplantation.

PMID- 29455424
TI  - Hypo-fractionated stereotactic radiation therapy for lung malignancies by means
      of helical tomotherapy: report of feasibility by a single-center experience.
AB  - BACKGROUND: Several experiences in the literature report SBRT as an effective
      treatment option for medically inoperable early stage non-small cell lung cancer
      (NSCLC) and oligometastatic disease. The optimal fractionation schedules and
      total dose remain controversial. In this study, we evaluated the safety in terms
      of toxicity and efficacy of using of 8-10 fractions schedules with Helical
      Tomotherapy (HT) for primary and metastatic lung lesions. METHODS: Between March
      2014 and May 2016, a total of 39 patients (median age 72 years, range 26-91) were
      treated with HT-SBRT for malignant lung lesions: 22 patients with early stage
      NSCLC, 17 with oligometastases. Patients received 8-10 fractions with lower daily
      dose for central and ultracentral lesions. Treatment-related toxicity was
      evaluated using CTCAE v 4.0 scale. Local control (LC), overall survival (OS) and
      toxicity rates were prospectively collected. RESULTS: Median duration of RT was
      15 days (range 10-26 days) and no interruption occurred. With a median follow-up
      of 13 months (range 3-29), we reported one G2 pneumonitis (2.6%) and one G2 chest
      pain (2.6%); no >= G2 esophagitis was registered. Actuarial local control rate
      was 95.5% both at 12 and 24 months for early stage NSCLC and 92.9% both at 12 and
      24 months for metastatic patients. OS rate was 94.4 and 92.3% at 1 year, and 94.4
      and 83.9% at 2 years in primary and metastatic group, respectively. CONCLUSIONS:
      The use of 8-10 fractions schedule HT-SBRT for lung malignancies results in high
      LC and OS rates with minimal toxicities reported.

PMID- 29455425
TI  - The risk of type 2 diabetes mellitus according to the categories of body mass
      index: the Korean Genome and Epidemiology Study (KoGES).
AB  - AIMS: Obesity is an established risk factor for type 2 diabetes mellitus (T2DM).
      However, there is limited information on the pattern of relationship between the
      risk for T2DM and body mass index (BMI) categories including underweight and
      overweight. Thus, this study was to evaluate the risk of T2DM according to BMI
      categories defined by Asian-specific cutoff of BMI. METHODS: 7660 non-diabetic
      Koreans were grouped into five BMI categories (underweight, normal, overweight,
      obese and severe obese) defined by Asian-specific cutoff of BMI and followed up
      for 10 years to monitor the development of T2DM. With a reference of normal BMI
      group, Cox proportional hazards assumption was used to calculate hazard ratios
      (HRs) and their 95% confidence intervals for T2DM in five groups. Subgroup
      analysis was conducted by gender and age (40-59 years and 60-69 years). RESULTS:
      Baseline mean value of metabolic factors like fasting glucose, HOMA-IR, total
      cholesterol and the proportion of impaired fasting glucose increased
      proportionally to the level of BMI categories. Underweight group had the higher
      proportion of impaired glucose tolerance than normal and overweight group. In all
      subgroups, underweight, overweight, obese and severe obese group had the higher
      HRs for T2DM than normal group, but statistical significance was only found in
      overweight, obese and severe obese group. CONCLUSIONS: The risk of T2DM tends to
      increase proportionally to the level of BMI categories from overweight to severe
      obese group. Further studies should be considered to identify the incidental
      relationship between underweight and T2DM.

PMID- 29455426
TI  - Work-loss years among people diagnosed with diabetes: a reappraisal from a life
      course perspective.
AB  - AIMS: Early exit from the workforce has been proposed to be one of the
      unfavorable consequences of diabetes. We examined whether early exit from the
      workforce differed between persons who were and were not diagnosed with diabetes
      during their work career. METHODS: The cohort included 12,726 individuals of the
      Helsinki Birth Cohort Study, born between 1934 and 1944. Using data from
      nationwide registers, the cohort was followed up from early adulthood until they
      transitioned into retirement or died. Work-loss years were estimated using the
      restricted mean work years method. RESULTS: During a follow-up of 382,328 person
      years for men and 349 894 for women, 36.8% transitioned into old age pension and
      63.2% exited workforce early. Among men, 40.5% of those with and 32.8% of those
      without diabetes transitioned into old age pension (p=0.003). The corresponding
      numbers for women were 48.6% and 40.4% (p = 0.013), respectively. Mean age at
      exit from the workforce was 60.1 (95% confidence interval [CI], 59.6 to 60.7)
      years among men with diabetes and 57.6 (95% CI, 57.2 to 58.0) years among men
      without diabetes (p = 0.016). Among women, corresponding ages were 61.4 (95% CI,
      60.8 to 61.9) years for those with diabetes and 59.5 (95% CI, 59.3 to 59.7) years
      for those without diabetes (p < 0.001). The difference in mean restricted work
      loss years according to diabetes was 2.5 (95% CI 0.5 to 4.6) for men and 1.9 (95%
      CI 1.0 to 2.8) for women. CONCLUSION: Among individuals followed up throughout
      their work career, those with a diabetes diagnosis exited the workforce
      approximately two years later compared to those without diabetes.

PMID- 29455427
TI  - Variation in cardiac markers and electrocardiographic alterations in young calves
      naturally infected with bovine tropical theileriosis.
AB  - The present study was designed to assess the deleterious effects of bovine
      tropical theileriosis on the cardiovascular system and the consequent myocardial
      involvement in young calves. Myocardial effects in parasitic diseases are often
      neglected. Hemolytic anemia, associated secondary hypoxia, and vasculitis are
      cardinal features of bovine theileriosis. In the present study, electrocardiogram
      (ECG) alongside serum cardiac troponin I (cTnI) and creatinine phosphokinase
      myocardial band (CPK-MB) concentrations were analyzed in infected, treated, and
      control groups of young calves. Non-significant alterations were noticed in ECG.
      However, certain signs like sinus tachycardia, first-degree AV block, atrial
      premature complex, left atrial hypertrophy, and right atrial hypertrophy were
      found on consistent basis in infected calves. A significant increase in the serum
      concentration levels of cTnI and CPK-MB was noticed in infected calves followed
      by significant fall in both these biomarkers post treatment. cTnI and CPK-MB can
      definitely be used as myocardial markers in theileriosis-affected animals.

PMID- 29455428
TI  - Potential of feeding beef cattle with whole corn crop silage and rice straw in
      Malaysia.
AB  - The potential of using whole corn crop silage and rice straw as an alternative
      feed for the beef cattle based on the intake and growth performance were
      evaluated. Using randomised completely block design, nine adult Mafriwal cattle
      were blocked intro three groups and treated with three different forage diets
      supplemented with 20% pelleted palm kernel cake on dry matter basis. The
      treatments were 100% rice straw (RS), 100% corn silage (CS) and an equal mixture
      of rice straw and corn silage (MIX) fed ad libitum. The animals were housed in
      individual pens, and the feeding trial was conducted for 12 weeks with 2 weeks of
      adaptation period. The results showed that CS had the best feed nutritive
      composition with the lowest concentration of highly indigestible fibre and the
      highest concentration of organic matter and energy. The CS also had the highest
      intake, and the corn silage inclusion in MIX managed to improve the intake on par
      with CS in terms of the dry matter intake of body weight (DMI of BW), voluntary
      intake (VI) and crude protein (CP) intake. Cattle fed with CS gave the highest
      and most stable BW gain with an average daily gain (ADG) of 808 g/day rivalling
      cross-bred cattle fed with high amount of concentrates. The all straw diet (RS)
      supplemented with PKC recorded a positive ADG of 133 g/day while the MIX gave 383
      g/day matching total Napier grass diet.

PMID- 29455429
TI  - Predictive Performance of Physiologically-Based Pharmacokinetic Models in
      Predicting Drug-Drug Interactions Involving Enzyme Modulation.
AB  - BACKGROUND: Physiologically-based pharmacokinetic (PBPK) modeling in predicting
      metabolic drug-drug interactions (mDDIs) is routinely used in drug development.
      Currently, the US FDA endorses the use of PBPK to potentially support dosing
      recommendations for investigational drugs as enzyme substrates of mDDIs, and to
      inform a lack of mDDIs for investigational drugs as enzyme modulators. METHODS:
      We systematically evaluated the performance of PBPK modeling in predicting mDDIs
      published in the literature. Models developed to assess both investigational
      drugs as enzyme substrates (Groups 1 and 2, as being inhibited and induced,
      respectively) or enzyme modulators (Groups 3 and 4, as inhibitors and inducers,
      respectively) were evaluated. Predicted ratios of the area under the curve
      (AUCRs) and/or maximum plasma concentration (CmaxRs) with and without
      comedication were compared with the observed ratios. RESULTS: For Groups 1, 2, 3,
      and 4, 62, 50, 44, and 43% of model-predicted AUCRs, respectively, were within a
      predefined threshold of 1.25-fold of observed values (0.8-1.25x). When the
      threshold was widened to twofold, the values increased to 100, 80, 81, and 86%
      (0.5-2.0x). For Groups 3 and 4, prediction for mDDI liability (the existence or
      lack of mDDIs) using PBPK appears to be satisfactory. CONCLUSION: Our analysis
      supports the FDA's current recommendations on the use of PBPK to predict mDDIs.

PMID- 29455430
TI  - Existential Meaning of Patients with Chronic Facial Pain.
AB  - Coping strategies are necessary to deal with pain, one of the most disabling
      conditions. Treatments are often refractory, and the elaboration of existential
      meaning is necessary to live with residual pain. The objective of this study was
      to discuss the relevance of the meaning of life in coping with refractory chronic
      neuropathic facial pain according to singular cases. Each patient is unique and
      needs a singular approach to understand and treat the pain phenomenon. Self
      transcendence, existential issues and philosophical values are central concepts
      to assess chronic conditions and should be highlighted in medical practice these
      days.

PMID- 29455431
TI  - Menstrual phase and the vascular response to acute resistance exercise.
AB  - INTRODUCTION: Aerobic exercise has a favorable effect on systemic vascular
      function, reducing both central (large elastic artery) and peripheral (smaller
      muscular artery) stiffness. The effects of resistance exercise (RE) on arterial
      stiffness are more complex. Acute RE increases central artery stiffness while
      decreasing peripheral stiffness. To date, the majority of studies have been
      performed in predominantly male participants. PURPOSE: To examine the effect of
      acute RE on central and peripheral arterial stiffnesses in women, a secondary
      purpose was to explore the influence of cyclic changes in estrogen status across
      the menstrual cycle on the arterial response to acute RE. METHODS: 18 healthy
      women [28 +/- 7 years, body mass index (BMI) 22.6 +/- 2.9 kg/m2] completed an
      acute RE bout during the early follicular and the early luteal phase of their
      menstrual cycle. Salivary 17beta-Estradiol concentration was measured during each
      phase, using a passive drool technique. Pulse-wave velocity (PWV) was obtained
      from the carotid-femoral and carotid-radial pulse sites to measure central and
      peripheral stiffness, respectively, using applanation tonometry. PWV was measured
      at rest, immediately, 10, 20, and 30 min post-RE. RESULTS: 17beta-Estradiol
      concentration was significantly lower in the early follicular vs. the early
      luteal phase of the menstrual cycle (1.78 +/- 0.51 vs. 2.40 +/- 0.26 pg/ml, p =
      0.01). Central PWV significantly increased (p < 0.05) and peripheral PWV
      significantly decreased (p < 0.05) post-RE in both the early follicular and early
      luteal phases. No phase-by-time interaction was detected for either vascular
      segment (p > 0.05). CONCLUSION: Women experience increases in central arterial
      stiffness and reductions in peripheral arterial stiffness following acute RE.
      Menstrual cycle phase may not influence changes in arterial stiffness in response
      to acute RE.

PMID- 29455432
TI  - Serum miRNA-27a and miRNA-18b as potential predictive biomarkers of hepatitis C
      virus-associated hepatocellular carcinoma.
AB  - Hepatitis C virus (HCV) infection remains the main risk factor for chronic
      hepatitis (CHC), liver cirrhosis, and hepatocellular carcinoma (HCC). Changes in
      microRNA (miRNA) profiles can be associated with HCV infection and may either
      favor or inhibit the virus and/or its complication. Moreover, miRNAs have emerged
      as key regulators of various cancers including HCC. The aim of this work was to
      investigate the potentail role of miRNA-27a and miRNA-18b expression levels as
      non-invasive predictive biomarkers of hepatitis C virus-associated HCC.
      Furthermore, we aimed to explore potential association of these miRNAs
      expressions with HCC clinicopathological features' in Egyptian cases. This case
      control study included 200 participants [60 CHC patients, 39 post-HCV cirrhosis
      patients, 51 HCC cases], and 50 healthy volunteers. The serum miRNA-27a and miRNA
      18b expression profiles were measured using quantitative real time-polymerase
      chain reaction (qRT-PCR). miRNA-27a and miRNA-18b expression levels were
      significantly increased in post-hepatitis C cirrhosis cases compared to control
      and CHC groups. In HCC group, only miRNA-27a expression levels were significantly
      increased. Moreover, miRNA-27a and miRNA-18b expression levels were positively
      correlated with distant metastasis, Child-Pugh grade, and lymph node metastasis.
      Logistic regression analysis revealed that miRNA-27a expression was an
      independent predictor of cirrhosis among CHC. Receiver operating characteristic
      (ROC) analyses showed that miRNA-27a and miRNA-18b expression levels were useful
      biomarkers discriminating cirrhosis from CHC (AUC were 0.672 and 0.487,
      respectively), and in differentiating HCC from post-hepatitis C cirrhosis (AUC
      were 0.897 and 0.723, respectively). By combined ROC analysis, power of miRNA-27a
      and miRNA-18b expression levels as discriminator between HCC from post-hepatitis
      C cirrhosis was high (AUC = 0.0.821). Serum microRNA-27a and miRNA-18b expression
      levels are promising diagnostic and non-invasive biomarkers of CHC, post-CHC
      cirrhosis, and HCC.

PMID- 29455433
TI  - Intracrine action of angiotensin II in mesangial cells: subcellular distribution
      of angiotensin II receptor subtypes AT1 and AT2.
AB  - Biological effects of angiotensin II (AngII) such as regulation of AngII target
      genes may be triggered by interaction of AngII with intracellular AngII receptor
      types 1 and 2 (AT1 and AT2), defined as intracrine response. The aim of this
      study was to examine the presence of AT1 and AT2 receptors in nuclear membrane of
      human mesangial cells (HMCs) and evaluate the possible biological effects
      mediated by intracellular AT1 through an intracrine mechanism. Subcellular
      distribution of AT1 and AT2 was evaluated by immunofluorescence and by western
      blot in isolated nuclear extract. Endogenous intracellular synthesis of AngII was
      stimulated by high glucose (HG). Effects of HG were analyzed in the presence of
      candesartan, which prevents AngII internalization. Both receptors were found in
      nuclear membrane. Fluorescein isothiocyanate (FITC)-labeled AngII added to
      isolated nuclei produced a fluorescence that was reduced in the presence of
      losartan or PD-123319 and quenched in the presence of both inhibitors
      simultaneously. HG induced overexpression of fibronectin and increased cell
      proliferation in the presence of candesartan, indicating an intracrine action of
      AngII induced by HG. Results showed the presence of nuclear receptors in HMCs
      that can be activated by AngII through an intracrine response independent of
      cytoplasmic membrane AngII receptors.

PMID- 29455434
TI  - Elucidating post-translational regulation of mouse CREB3 in Neuro2a cells.
AB  - CREB3 is an ER membrane-bound transcription factor; however, post-translational
      regulation of CREB3, including expression, processing, and activation, is not
      fully characterized. We therefore constructed several types of mouse CREB3
      expression genes and elucidated their expression in Neuro2a cells by treatment
      with stimuli and co-transfection with genes associated with ER-Golgi homeostasis,
      such as mutant Sar1 [H79G], GRP78, and KDEL receptor 1 (KDELR1). Interestingly,
      treatment of Neuro2a cells expressing Flag-tagged full-length CREB3 with monensin
      and nigericin induced the expression of the approximately 50 kDa N-terminal
      fragment; however, its cleavage was not parallel to the levels of GADD153 and LC3
      II. Co-transfection of full-length CREB3 together with Sar1 [H79G], GRP78, or
      KDELR1 showed that only Sar1 [H79G] induced expression of the cleaved form, and
      KDELR1 dramatically decreased the expression of the full-length form.
      Accordingly, Sar1 [H79G]- and KDELR1-overexpression influenced GAL4-CREB3
      dependent luciferase activities. To understand the activation of CREB3 under more
      pathophysiological conditions, we focused on the effect of metal ions on CREB3
      cleavage in Neuro2a cells. Among the six metal ions we tested, only copper ion
      stabilized full-length CREB3 expression. Copper ion also increased its N-terminal
      form and GAL4-CREB3-dependent luciferase activity, which was accompanied by the
      increase in the ubiquitinated proteins in Neuro2a cells. Taken together, CREB3
      expression is regulated by multiple ER-Golgi resident factors in a post
      translational manner, but its processing is not directly associated with ER
      stress and autophagic dysfunction. This finding is especially true for the unique
      action of the copper ion on CREB3 stabilization and processing in parallel to
      aberration of ubiquitin-proteasome system, which might provide new insights into
      understanding the mechanisms of intractable disorders.

PMID- 29455435
TI  - DNA methylation regulated microRNAs in HPV-16-induced head and neck squamous cell
      carcinoma (HNSCC).
AB  - INTRODUCTION: Epigenetic modifications have been reported to play an important
      role in regulating gene expression and these modifications become critical when
      they have a role in controlling another important layer of epigenetic regulation
      namely microRNAs. In the present study, we have identified the microRNAs that may
      be regulated by promoter DNA methylation and histone acetylation in Human
      papilloma virus-positive head and neck squamous cell carcinoma. METHODOLOGY: HPV
      negative cell line (UPCI:SCC-116) and HPV-16 +ve cell line (UPCI:SCC-090) were
      treated with methylation inhibitor (5-aza-2'-deoxycytidine, AZA) and acetylation
      inhibitor (Trichostatin-A, TSA), followed by micro-array analysis. The
      differentially expressed miRNAs were validated in control (n = 10), HPV-16 +ve (n
      = 30), and HPV -ve (n = 30) HNC, TCGA (n = 529) tissue samples, and two HPV -ve
      (SCC116 and Hacat) and two HPV +ve (SCC090 and SiHa) cell lines. Methylation
      specific PCR (MSP) and chromatin immunoprecipitation assay (CHIP) were performed
      to validate their regulation. In silico and in vitro analyses of identified
      miRNAs were done to study putative pathways they target and their possible role
      in carcinogenesis. RESULTS: Among 10 miRNAs specifically up-regulated in
      microarray analysis of AZA-treated SCC090 cells, we observed significantly
      decreased expression of hsa-miR-181c-5p, hsa-miR-132-5p, hsa-miR-658 in HPV +ve
      HNC cohort, TCGA tissue samples, and cell lines as compared to their HPV -ve
      counterpart, and their promoter region also possesses CpG islands. MSP and
      analysis of TCGA data (MethHC) revealed increased frequency of methylation at the
      promoter of hsa-miR-132-5p that is negatively correlated with its expression. In
      TSA-treated SCC090 cells, out of 7 miRNAs, two namely Hsa-miR-129-2-3p and Hsa
      miR-449a were found to be up-regulated as compared to HPV -ve cells. However, the
      levels of enrichment by anti-acetyl-H3 and anti-acetyl-H4 were significantly low
      in cell lines compared to respective controls and both were up-regulated in HPV
      +ve compared to HPV -ve TCGA tissue samples. In silico analysis revealed hsa-miR
      132-5p targeted canonical beta-catenin/wnt pathway and modulation of down-stream
      genes of the pathway was observed on over-expression/inhibition of hsa-miR-132
      5p. CONCLUSION: This study suggests the role of epigenetic modifications in
      regulating expression of miRNAs in HPV +ve HNSCC.

PMID- 29455436
TI  - Older adults in jail: high rates and early onset of geriatric conditions.
AB  - BACKGROUND: The number of older adults in the criminal justice system is rapidly
      increasing. While this population is thought to experience an early onset of
      aging-related health conditions ("accelerated aging"), studies have not directly
      compared rates of geriatric conditions in this population to those found in the
      general population. The aims of this study were to compare the burden of
      geriatric conditions among older adults in jail to rates found in an age-matched
      nationally representative sample of community dwelling older adults. METHODS:
      This cross sectional study compared 238 older jail inmates age 55 or older to
      6871 older adults in the national Health and Retirement Study (HRS). We used an
      age-adjusted analysis, accounting for the difference in age distributions between
      the two groups, to compare sociodemographics, chronic conditions, and geriatric
      conditions (functional, sensory, and mobility impairment). A second age-adjusted
      analysis compared those in jail to HRS participants in the lowest quintile of
      wealth. RESULTS: All geriatric conditions were significantly more common in jail
      based participants than in HRS participants overall and HRS participants in the
      lowest quintile of net worth. Jail-based participants (average age of 59)
      experienced four out of six geriatric conditions at rates similar to those found
      in HRS participants age 75 or older. CONCLUSIONS: Geriatric conditions are
      prevalent in older adults in jail at significantly younger ages than non
      incarcerated older adults suggesting that geriatric assessment and geriatric
      focused care are needed for older adults cycling through jail in their 50s and
      that correctional clinicians require knowledge about geriatric assessment and
      care.

PMID- 29455437
TI  - Live donor liver transplantation for acute liver failure: A single center
      experience.
AB  - INTRODUCTION: Acute liver failure (ALF) is an indication for emergency liver
      transplantation (LT). Although centers performing only deceased donor liver
      transplants (DDLT) have shown improved outcomes in this situation, they still
      have relatively long waiting lists. An alternative would be living donor liver
      transplantation (LDLT), which has shown equivalent outcomes in the elective
      situation but there is limited evidence of its results in ALF. AIM: The purpose
      of this study was to assess the outcomes in patients with ALF undergoing
      emergency LDLT in our center in Delhi, India. METHODS: We prospectively collected
      data on 479 patients who underwent LT in our hospital between January 2009 and
      December 2015 to evaluate the outcomes of those with ALF. The ALF patients were
      listed for transplantation after they met the Kings' College criteria and rapid
      evaluation was done following a protocol consisting of three phases. Patients
      with grade III/IV encephalopathy were put on mechanical ventilation. Data
      regarding their postoperative course, morbidity, and mortality were analyzed.
      RESULTS: Thirty-six (7.5%) out of the 479 patients underwent emergency LT for
      ALF. Their mean age was 27.5 years (range 4-59 years) and the male to female
      ratio of 2:3. Preoperative intubation was required in 15 of 25 patients who had
      encephalopathy. Wilson's disease was the most common cause of ALF in children
      while in adults, it was acute viral hepatitis. The time interval between listing
      and transplantation was a mean of 36 +/- 12.4 h. The mean graft to recipient
      weight ratio (GRWR) was 1.06 +/- 0.3. The recipients were extubated
      postoperatively after a mean period of 2.6 days and their mean ICU stay was 6.3
      days. Postoperative infection was the most common complication and required
      upgradation of antifungal and antibiotic treatments. Neurological complications
      occurred in five patients. Thirty-one of 36 (86.1%) patients survived and
      progressive cerebral edema and sepsis were the most common causes of mortality.
      Patients who died had higher model for end-stage liver disease scores, longer
      cold ischemia time (CIT), and higher grades of encephalopathy (though 80%
      patients with encephalopathy survived). There was no donor mortality. At long
      term follow up of a median of 56 months, 29 (80.5%) of 36 patients were still
      alive. CONCLUSIONS: In our experience, LDLT is an alternative procedure to DDLT
      in patients with ALF and is associated with good outcomes even in patients with
      high grades of encephalopathy.

PMID- 29455438
TI  - Letter to the editor in response to: The role of preoperative C-reactive protein
      and procalcitonin as predictors of post-pancreaticoduodenectomy infective
      complications: A prospective observational study.

PMID- 29455439
TI  - Role of noninvasive markers to predict the presence of esophageal varices in
      cirrhosis: Pilot study.

PMID- 29455440
TI  - Computer Aided Solution for Automatic Segmenting and Measurements of Blood
      Leucocytes Using Static Microscope Images.
AB  - Blood leucocytes segmentation in medical images is viewed as difficult process
      due to the variability of blood cells concerning their shape and size and the
      difficulty towards determining location of Blood Leucocytes. Physical analysis of
      blood tests to recognize leukocytes is tedious, time-consuming and liable to
      error because of the various morphological components of the cells. Segmentation
      of medical imagery has been considered as a difficult task because of complexity
      of images, and also due to the non-availability of leucocytes models which
      entirely captures the probable shapes in each structures and also incorporate
      cell overlapping, the expansive variety of the blood cells concerning their shape
      and size, various elements influencing the outer appearance of the blood
      leucocytes, and low Static Microscope Image disparity from extra issues outcoming
      about because of noise. We suggest a strategy towards segmentation of blood
      leucocytes using static microscope images which is a resultant of three
      prevailing systems of computer vision fiction: enhancing the image, Support
      vector machine for segmenting the image, and filtering out non ROI (region of
      interest) on the basis of Local binary patterns and texture features. Every one
      of these strategies are modified for blood leucocytes division issue, in this
      manner the subsequent techniques are very vigorous when compared with its
      individual segments. Eventually, we assess framework based by compare the outcome
      and manual division. The findings outcome from this study have shown a new
      approach that automatically segments the blood leucocytes and identify it from a
      static microscope images. Initially, the method uses a trainable segmentation
      procedure and trained support vector machine classifier to accurately identify
      the position of the ROI. After that, filtering out non ROI have proposed based on
      histogram analysis to avoid the non ROI and chose the right object. Finally,
      identify the blood leucocytes type using the texture feature. The performance of
      the foreseen approach has been tried in appearing differently in relation to the
      system against manual examination by a gynaecologist utilizing diverse scales. A
      total of 100 microscope images were used for the comparison, and the results
      showed that the proposed solution is a viable alternative to the manual
      segmentation method for accurately determining the ROI. We have evaluated the
      blood leucocytes identification using the ROI texture (LBP Feature). The
      identification accuracy in the technique used is about 95.3%., with 100
      sensitivity and 91.66% specificity.

PMID- 29455441
TI  - A proactive transfer policy for critical patient flow management.
AB  - Hospital emergency departments are often overcrowded, resulting in long wait
      times and a public perception of poor attention. Delays in transferring patients
      needing further treatment increases emergency department congestion, has negative
      impacts on their health and may increase their mortality rates. A model built
      around a Markov decision process is proposed to improve the efficiency of patient
      flows between the emergency department and other hospital units. With each day
      divided into time periods, the formulation estimates bed demand for the next
      period as the basis for determining a proactive rather than reactive transfer
      decision policy. Due to the high dimensionality of the optimization problem
      involved, an approximate dynamic programming approach is used to derive an
      approximation of the optimal decision policy, which indicates that a certain
      number of beds should be kept free in the different units as a function of the
      next period demand estimate. Testing the model on two instances of different
      sizes demonstrates that the optimal number of patient transfers between units
      changes when the emergency patient arrival rate for transfer to other units
      changes at a single unit, but remains stable if the change is proportionally the
      same for all units. In a simulation using real data for a hospital in Chile,
      significant improvements are achieved by the model in key emergency department
      performance indicators such as patient wait times (reduction higher than 50%),
      patient capacity (21% increase) and queue abandonment (from 7% down to less than
      1%).

PMID- 29455442
TI  - In Search of Executive Impairment in Pathological Gambling: A Neuropsychological
      Study on Non-treatment Seeking Gamblers.
AB  - Pathological gambling is characterized by a persisting maladaptive and recurrent
      behavior with severe social and psychological consequences. There is evidence of
      strong comorbidity with psychiatric manifestations as well as cognitive mainly
      involving executive functions. This study aimed to investigate impairment in
      executive functions and working memory, and personality traits in a sample of
      Greek gamblers. Twenty-four men involved in various gambling activities were
      recruited from ecological settings as probable pathological gamblers. They were
      assessed with a comprehensive neuropsychological battery involving several
      executive tasks, the Zuckerman-Kuhlman Personality Questionnaire, the Hospital
      Anxiety Depression Scale, and the Difficulties in Emotion Regulation Scale. An
      age- and education-level matched group of 21 men without history of habitual
      gambling served as controls. As a group, gamblers displayed significantly lower
      scores on indices of inhibition, decision making and self-reported emotional
      awareness, and scored higher on impulsivity/sensation seeking personality traits.
      Notably, gamblers scored similarly or significantly higher on measures of verbal
      and visuospatial working memory, cognitive flexibility, processing speed, verbal
      fluency, and sustained attention. Overall, we argue that gamblers do present with
      specific cognitive deficits, but there is no evidence for a generalized executive
      impairment, and further stress the importance of investigating cognitive,
      personality, and psychiatric aspects of gambling on the basis of an ecologically
      valid sampling.

PMID- 29455443
TI  - Narcissistic Implications in Gambling Disorder: The Mediating Role of Emotion
      Dysregulation.
AB  - Gambling Disorder (GD) is a complex psychopathology involving a numbers of
      cognitive, behavioral, emotional and neurobiological determinants. Previous
      research suggests that GD may frequently co-occur with Narcissistic Personality
      Disorder. However, there is still a lack of study investigating Pathological
      Narcissism (PN) in both its vulnerable and grandiose facets among clinical
      population. Moreover, emotional dysregulation is commonly thought to underlie GD
      albeit research on this topic remains poor. The present study aims to investigate
      the role of both vulnerable and grandiose narcissism in relation to GD as well as
      the mediator role played by emotion dysregulation in such link. We administered
      to a sample of addicted gamblers (n = 74) and a sample of heathy controls (n =
      105), the South Oaks Gambling Screen (SOGS), the Pathological Narcissism
      Inventory (PNI) and the Difficulties in Emotion Regulation Scale (DERS).
      Differences across groups emerged on the scores obtained on the PNI and DERS.
      Moreover, we found positive associations between SOGS scores and both PNI and
      DERS. Also, strategic addicted gamblers showed higher levels of vulnerable
      narcissism compared to others. Finally, emotion dysregulation difficulties
      appeared to fully mediate the relationship between grandiose narcissism and GD
      severity. Grandiose and vulnerable narcissism appear important variables involved
      in GD. Also, emotion regulation deficits seem to account for GD and to explain
      the pathways by which grandiose narcissism leads to GD. Clinical implications and
      future directions are discussed.

PMID- 29455444
TI  - Persistent left superior vena cava with thrombus formed in the catheter lumen 4 h
      after dialysis catheter placed.
AB  - Persistent left superior vena cava (PLSVC) is one of the most common thoracic
      venous anomaly and rarely noticed, because it is asymptomatic. However, for
      nephrologists, it is frequent enough to be encountered while placing hemodialysis
      catheters through the jugular vein. We report the case of 66-year-old patient
      with PLSVC presenting intrinsic thrombosis formation 4 h after dialysis catheter
      placed. Dialysis catheter was placed in the left internal jugular vein without
      resistance and any complication. PLSVC was detected after dialysis catheter
      insertion. We decided to remove the catheter, because the patient has other veins
      in which the catheter can be placed. When it was removed 4 h after catheter
      placing, thrombus was recognized in the catheter lumen. Transesophageal
      echocardiography was performed and no thrombus formation was observed in the
      heart chamber. For patients with PLSVC, if there were other veins in which the
      catheter can be placed, catheter replacement should be considered.

PMID- 29455445
TI  - Adaptive reinventing: implicit bias and the co-construction of social change.
AB  - Emerging research on implicit bias recognition and management within health
      professions describes individually focused educational interventions without
      considering workplace influences. Workplace learning theories highlight how
      individual agency and workplace structures dynamically interact to produce change
      within individuals and learning environments. Promoting awareness of individual
      biases shaped by clinical learning environments may therefore represent a unique
      type of workplace learning. We sought to explore how individuals and the
      workplace learning environment interact once awareness of implicit biases are
      triggered within learners. In accordance with longitudinal case study methodology
      and informed by constructivist grounded theory, we conducted multiple
      longitudinal interviews with physician and nurse participants over 12 months. Our
      results suggest that implicit bias recognition provokes dissonance among
      participants leading to frustration, and critical questioning of workplace
      constraints. Once awareness is triggered, participants began reflecting on their
      biases and engaging in explicit behavioural changes that influenced the
      perception of structural changes within the learning environment itself.
      Collaboration, communication and role modeling within teams appeared to
      facilitate the process as individual and workplace affordances were gradually
      transformed. Our findings suggest a potential model for understanding how
      individual learners adaptively reinvent their role in response to disruptions in
      their learning environment.

PMID- 29455446
TI  - BIG2-ARF1-RhoA-mDia1 Signaling Regulates Dendritic Golgi Polarization in
      Hippocampal Neurons.
AB  - Proper dendrite development is essential for establishing neural circuitry, and
      Rho GTPases play key regulatory roles in this process. From mouse brain lysates,
      we identified Brefeldin A-inhibited guanine exchange factor 2 (BIG2) as a novel
      Rho GTPase regulatory protein involved in dendrite growth and maintenance. BIG2
      was highly expressed during early development, and knockdown of the ARFGEF2 gene
      encoding BIG2 significantly reduced total dendrite length and the number of
      branches. Expression of the constitutively active ADP-ribosylation factor 1 ARF1
      Q71L rescued the defective dendrite morphogenesis of ARFGEF2-null neurons,
      indicating that BIG2 controls dendrite growth and maintenance by activating ARF1.
      Moreover, BIG2 co-localizes with the Golgi apparatus and is required for Golgi
      deployment into major dendrites in cultured hippocampal neurons. Simultaneous
      overexpression of BIG2 and ARF1 activated RhoA, and treatment with the RhoA
      activator lysophosphatidic acid in neurons lacking BIG2 or ARF1 increased the
      number of cells with dendritic Golgi, suggesting that BIG2 and ARF1 activate RhoA
      to promote dendritic Golgi polarization. mDia1 was identified as a downstream
      effector of BIG2-ARF1-RhoA axis, mediating Golgi polarization and dendritic
      morphogenesis. Furthermore, in utero electroporation of ARFGEF2 shRNA into the
      embryonic mouse brain confirmed an in vivo role of BIG2 for Golgi deployment into
      the apical dendrite. Taken together, our results suggest that BIG2-ARF1-RhoA
      mDia1 signaling regulates dendritic Golgi polarization and dendrite growth and
      maintenance in hippocampal neurons.

PMID- 29455447
TI  - The continuum of breast cancer care and outcomes in the U.S. Military Health
      System: an analysis by benefit type and care source.
AB  - PURPOSE: This study investigates transition rates between breast cancer
      diagnosis, recurrence, and death by insurance benefit type and care source in
      U.S. Military Health System (MHS). METHODS: The MHS data repository and central
      cancer registry linked data were used to identify women aged 40-64 with
      histologically confirmed breast cancer between 2003 and 2007. Three-state
      continuous time Markov models were used to estimate transition rates and
      transition rate ratios (TRRs) by TRICARE benefit type (Prime or non-Prime) and
      care source (direct, purchased, or both), adjusted for demographic, tumor, and
      treatment variables. RESULTS: Analyses included 2668 women with transitions from
      diagnosis to recurrence (n = 832), recurrence to death (n = 79), and diagnosis to
      death without recurrence (n = 91). Compared to women with Prime within each care
      source, women with non-Prime using both care sources had higher transition rates
      (TRR 1.47, 95% CI 1.03, 2.10). Compared to those using direct care within each
      benefit type, women utilizing both care sources with non-Prime had higher
      transition rates (TRR 1.86, 95% CI 1.11, 3.13), while women with Prime utilizing
      purchased care had lower transition rates (TRR 0.82, 95% CI 0.68, 0.98).
      CONCLUSIONS: In the MHS, women with non-Prime benefit plans compared to Prime had
      higher transition rates along the breast cancer continuum among both care source
      users. Purchased care users had lower transition rates than direct care users
      among Prime beneficiaries. IMPLICATIONS FOR CANCER SURVIVORS: Benefit plan and
      care source may be associated with breast cancer progression. Further research is
      needed to demonstrate differences in survivorship.

PMID- 29455448
TI  - Editorial.

PMID- 29455450
TI  - Update: evidence of a broad histamine footprint on the human exercise
      transcriptome.

PMID- 29455449
TI  - Role of Exosomes Derived from miR-133b Modified MSCs in an Experimental Rat Model
      of Intracerebral Hemorrhage.
AB  - Intracerebral hemorrhage (ICH) has poor outcomes due to high mortality and
      morbidity, but until now, the effective treatments remain limited. MicroRNAs
      (miRNAs) are vital regulators of gene expression and demonstrated to be linked to
      the pathogenesis of various central nervous system (CNS) diseases. Exosomes are
      considered as cell-to-cell communication vectors and secreted largely by
      mesenchymal stromal cells (MSCs). The present study investigated the role of miR
      133b delivered by exosomes secreted from MSCs to brain tissues in rats after ICH.
      An autologous arterial blood ICH model in adult male Sprague-Dawley (SD) rats was
      used in this study. At 72 h after transfection with miR-133b mimics in MSCs, miR
      133b-modified MSC-derived exosomes were collected from medium of MSCs and then
      injected to rats via tail vein. The levels of miR-133b in secreted exosomes and
      brain tissues of rats in various groups and the levels of RhoA, phosphorylations
      of extracellular signal regulating kinase (ERK1/2), and cAMP response element
      binding protein (CREB) were detected by real-time PCR and western blot analysis,
      respectively. The effects of miR-133b on neuronal apoptosis and degeneration were
      respectively evaluated by TUNEL and fluoro-jade B staining. The miR-133b levels
      were reduced in brain tissues of rats at 24 h and peaked at 72 h after ICH. At 24
      h after miR-133b-modified exosome administration, the level of miR-133b was
      significantly increased, while the apoptotic and neurodegenerative neurons were
      obviously reduced in brain tissues after ICH. The results of western blot
      analysis showed that miR-133b modified exosomes treatment remarkably suppressed
      RhoA expression and activated ERK1/2/CREB in brain tissues after ICH.
      Collectively, our investigation suggested that exosomes derived from miR-133b
      modified MSCs exhibited neuroprotective role for anti-apoptotic effect of miR
      133b mediating RhoA and ERK1/2/CREB in rats after ICH.

PMID- 29455451
TI  - Both B-1a and B-1b cells exposed to Mycobacterium tuberculosis lipids
      differentiate into IgM antibody-secreting cells.
AB  - Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The
      cellular immune response to mycobacteria has been characterized extensively, but
      the antibody response remains underexplored. The present study aimed to examine
      whether host or bacterial phospholipids induce secretion of IgM, and specifically
      anti-phospholipid IgM, antibodies by B cells and to identify the responsible B
      cell subset. Here we show that peritoneal B cells responded to lipid antigens by
      secreting IgM antibodies. Specifically, stimulation with M. tuberculosis H37Rv
      total lipids resulted in significant induction of total and anti
      phosphatidylcholine IgM. Similarly, IgM antibody production increased
      significantly with stimulation by whole Mycobacterium bovis bacillus Calmette
      Guerin. The B-1 subset was the dominant source of IgM antibodies after exposure
      to cardiolipin. Both CD5+ B-1a and CD5- B-1b cell subsets secreted total IgM
      antibodies after exposure to M. tuberculosis H37Rv total lipids in vitro.
      Overall, our results suggest that the poly-reactive B-1 cell repertoire
      contributes to non-specific anti-phospholipid IgM antibody secretion in response
      to M. tuberculosis lipids.

PMID- 29455453
TI  - Homelessness and Emergency Medicine: Where Do We Go From Here?

PMID- 29455452
TI  - Cannabinoids in arterial, pulmonary and portal hypertension - mechanisms of
      action and potential therapeutic significance.

PMID- 29455455
TI  - Cerebrospinal fluid total protein determination in acute and chronic inflammatory
      demyelinating polyneuropathies: a critical reappraisal.

PMID- 29455456
TI  - Seasonal acclimatization of thallus proline contents of Mastocarpus stellatus and
      Chondrus crispus: intertidal rhodophytes that differ in freezing tolerance.
AB  - Mastocarpus stellatus and Chondrus crispus often co-occur in the lower intertidal
      of Northern Atlantic rocky shorelines. At our field site along the Maine coast
      (USA), Mastocarpus stellatus thalli possessed greater contents of proline when
      compared with thalli of Chondrus crispus. In addition, M. stellatus thalli
      acclimated to colder growth conditions in winter/early spring by increasing
      proline content several fold; no seasonal acclimation in proline content was
      observed in C. crispus. Proline accumulates in the tissues of a broad diversity
      of freezing-tolerant organisms and is among the most common cryoprotectant
      molecules. Thus, our observations provide a basis for the previously well
      documented greater freezing tolerance of Mastocarpus stellatus when compared with
      Chondrus crispus.

PMID- 29455454
TI  - Oxidative capacity varies along the length of healthy human tibialis anterior.
AB  - KEY POINTS: During exercise skeletal muscles use the energy buffer
      phosphocreatine. The post-exercise recovery of phosphocreatine is a measure of
      the oxidative capacity of muscles and is traditionally assessed by 31 P magnetic
      resonance spectroscopy of a large tissue region, assuming homogeneous energy
      metabolism. To test this assumption, we collected spatially resolved spectra
      along the length of human tibialis anterior using a home-built array of 31 P
      detection coils, and observed a striking gradient in the recovery rate of
      phosphocreatine, decreasing along the proximo-distal axis of the muscle. A
      similar gradient along this muscle was observed in signal changes recorded by 1 H
      muscle functional MRI. These findings identify intra-muscular variation in the
      physiology of muscles in action and highlight the importance of localized
      sampling for any methodology investigating oxidative metabolism of this, and
      potentially other muscles. ABSTRACT: The rate of phosphocreatine (PCr) recovery
      (kPCr ) after exercise, characterizing muscle oxidative capacity, is
      traditionally assessed with unlocalized 31 P magnetic resonance spectroscopy
      (MRS) using a single surface coil. However, because of intramuscular variation in
      fibre type and oxygen supply, kPCr may be non-uniform within muscles. We tested
      this along the length of the tibialis anterior (TA) muscle in 10 male volunteers.
      For this purpose, we employed a 3T MR system with a 31 P/1 H volume transmit coil
      combined with a home-built 31 P phased-array receive probe, consisting of five
      coil elements covering the TA muscle length. Mono-exponential kPCr was determined
      for all coil elements after 40 s of submaximal isometric dorsiflexion (SUBMAX)
      and incremental exercise to exhaustion (EXH). In addition, muscle functional MRI
      (1 H mfMRI) was performed using the volume coil after another 40 s of SUBMAX. A
      strong gradient in kPCr was observed along the TA (P < 0.001), being two times
      higher proximally vs. distally during SUBMAX and EXH. Statistical analysis showed
      that this gradient cannot be explained by pH variations. A similar gradient was
      seen in the slope of the initial post-exercise 1 H mfMRI signal change, which was
      higher proximally than distally in both the TA and the extensor digitorum longus
      (P < 0.001) and strongly correlated with kPCr . The pronounced differences along
      the TA in functional oxidative capacity identify regional variation in the
      physiological demand of this muscle during everyday activities and have
      implications for the bio-energetic assessment of interventions to modify its
      performance and of neuromuscular disorders involving the TA.

PMID- 29455457
TI  - Authors' reply to the comment by Kendall et al.

PMID- 29455459
TI  - First draft genome of an iconic clownfish species (Amphiprion frenatus).
AB  - Clownfishes (or anemonefishes) form an iconic group of coral reef fishes,
      principally known for their mutualistic interaction with sea anemones. They are
      characterized by particular life history traits, such as a complex social
      structure and mating system involving sequential hermaphroditism, coupled with an
      exceptionally long lifespan. Additionally, clownfishes are considered to be one
      of the rare groups to have experienced an adaptive radiation in the marine
      environment. Here, we assembled and annotated the first genome of a clownfish
      species, the tomato clownfish (Amphiprion frenatus). We obtained 17,801 assembled
      scaffolds, containing a total of 26,917 genes. The completeness of the assembly
      and annotation was satisfying, with 96.5% of the Actinopterygii Benchmarking
      Universal Single-Copy Orthologs (BUSCOs) being retrieved in A. frenatus assembly.
      The quality of the resulting assembly is comparable to other bony fish
      assemblies. This resource is valuable for advancing studies of the particular
      life history traits of clownfishes, as well as being useful for population
      genetic studies and the development of new phylogenetic markers. It will also
      open the way to comparative genomics. Indeed, future genomic comparison among
      closely related fishes may provide means to identify genes related to the unique
      adaptations to different sea anemone hosts, as well as better characterize the
      genomic signatures of an adaptive radiation.

PMID- 29455458
TI  - Diagnosis, presentation and initial severity of Autoimmune Hepatitis (AIH) in
      patients attending 28 hospitals in the UK.
AB  - BACKGROUND & AIMS: There is limited information regarding patients with AIH
      outside relatively few large centres. We describe here the presenting features of
      patients with AIH, collected as part of an audit involving 28 UK hospitals.
      METHODS: Patients (incident since 1/1/2007 or prevalent since 1/1/2000) were >=18
      years and either met 1999 International AIH Group (IAIHG) diagnostic criteria (n
      = 1164), or received immunosuppressive therapy for clinically diagnosed AIH (n =
      103). RESULTS: Of 1267 patients (80% women, 91% Caucasian, age (median(range))
      55(8-86) years, 0.5% had acute viral hepatitis (CMV/EBV/HEV); 2% were taking
      Nitrofurantoin and 0.7% Khat. Twenty-one percent had clinical decompensation
      and/or a MELD score of >15. Time from first abnormal liver tests to diagnosis was
      >=1 year in 19% and was longer in jaundiced vs non-jaundiced patients. HBV and
      HCV serology were undocumented in 4%, serum immunoglobulins in 31% and
      autoantibodies in 11%-27%. When documented, >=1 antibody was present in 83%. LKM
      1-positive and autoantibody-negative patients had more severe disease.
      Histological cirrhosis was reported in 23%, interface hepatitis 88%, predominant
      lymphocytes/plasma cells 75%, rosettes 19% and emperipolesis 0.4%. Only 65% of
      those meeting 1999 IAIHG criteria also met simplified IAIHG criteria. University
      Hospitals compared to District General Hospitals, were more likely to report
      histological features of AIH. CONCLUSIONS: This cohort from across the UK is
      older than other multicentre AIH cohorts. One-fifth had decompensation or MELD
      >15. Diagnosis was delayed in 19%, diagnostic testing was incomplete in one-third
      and rosettes and emperipolesis were infrequently reported.

PMID- 29455460
TI  - One-year longitudinal study found a bidirectional relationship between physical
      activity and sleep disturbance in teenage Estonian girls.
AB  - AIM: Studies have shown that physical activity (PA) declines during adolescence,
      especially among girls. We examined the relationship between changes in PA and
      sleep disturbance over the school year, including any bidirectional relationship
      between these two factors. METHODS: This longitudinal study focused on teenage
      girls who had a mean age of 13.2 +/- 0.2 years at baseline and were drawn from
      five randomly selected schools in the city of Tartu, Estonia. Sleep disturbance
      and PA were subjectively assessed using the self-reported 3-Day Physical Activity
      Recall and the Insomnia Severity Index, at four intervals throughout the school
      year. Latent growth curve analyses were used to evaluate longitudinal and
      bidirectional associations between PA and sleep disturbance. RESULTS: Assessments
      were carried out at three-monthly intervals from September 2015 to June 2016.
      Sleep disturbance increased and PA decreased over the school year. At baseline,
      higher PA was related to lower sleep disturbance. Changes in PA corresponded with
      changes in sleep disturbance. A negative bidirectional relationship between sleep
      disturbance and PA over time was also found. CONCLUSION: These results suggest
      that increasing PA may be an effective strategy for improving the quality of
      sleep in girls during early adolescence.

PMID- 29455461
TI  - Population density mediates the interaction between pre- and postmating sexual
      selection.
AB  - When females mate with more than one male, sexual selection acts both before and
      after mating. The interaction between pre- and postmating episodes of selection
      is expected to be context dependent, but few studies have investigated how total
      sexual selection changes under different ecological conditions. We examined how
      population density mediates the interaction between pre- and postmating sexual
      selection by establishing replicate populations of the horned dung beetle
      Onthophagus taurus at low, medium, and high densities, and then using
      microsatellite-based parentage analyses to measure male fitness. We found that
      mating success and fertilization success were positively correlated at all three
      densities, but the strength of the correlation decreased with increasing density.
      We also found a shift from negative to positive linear selection on testes mass
      as density increased, and opposing selection on weapons and testes at high
      densities. These patterns suggest that the importance of postmating processes
      increases with increasing population density, which reduces the selective
      advantage of weapons for premating contest competition, and increases the
      selective advantage of large ejaculates for postmating sperm competition. We
      expect that density-dependent selection on testes mass has contributed to the
      phenotypic variation observed between natural populations of O. taurus that
      differ in density.

PMID- 29455462
TI  - Eggshell right atrial mass.

PMID- 29455463
TI  - Challenges of analyzing the global trade in CITES-listed wildlife.

PMID- 29455464
TI  - Disparities in second-generation DNA metabarcoding results exposed with
      accessible and repeatable workflows.
AB  - Different second-generation sequencing technologies may have taxon-specific
      biases when DNA metabarcoding prey in predator faeces. Our major objective was to
      examine differences in prey recovery from bat guano across two different
      sequencing workflows using the same faecal DNA extracts. We compared results
      between the Ion Torrent PGM and the Illumina MiSeq with similar library
      preparations and the same analysis pipeline. We focus on repeatability and
      provide an R Notebook in an effort towards transparency for future methodological
      improvements. Full documentation of each step enhances the accessibility of our
      analysis pipeline. We tagged DNA from insectivorous bat faecal samples, targeted
      the arthropod cytochrome c oxidase I minibarcode region and sequenced the product
      on both second-generation sequencing platforms. We developed an analysis pipeline
      with a high operational taxonomic unit (OTU) clustering threshold (i.e., >=98.5%)
      followed by copy number filtering to avoid merging rare but genetically similar
      prey into the same OTUs. With this workflow, we detected 297 unique prey taxa, of
      which 74% were identified at the species level. Of these, 104 (35%) prey OTUs
      were detected by both platforms, 176 (59%) OTUs were detected by the Illumina
      MiSeq system only, and 17 (6%) OTUs were detected using the Ion Torrent system
      only. Costs were similar between platforms but the Illumina MiSeq recovered six
      times more reads and four additional insect orders than did Ion Torrent. The
      considerations we outline are particularly important for long-term ecological
      monitoring; a more standardized approach will facilitate comparisons between
      studies and allow faster recognition of changes within ecological communities.

PMID- 29455465
TI  - Insulin-like growth factor 2: a poor prognostic biomarker linked to racial
      disparity in women with uterine carcinosarcoma.
AB  - The objective of this study was to investigate the relationship of insulin-like
      growth factor 2 (IGF2) expression and survival in women with uterine
      carcinosarcoma (UCS). Insulin-like growth factor 2 protein expression was
      determined by immunohistochemical staining of tumor tissues from 103 patients
      with UCS. The H-score (product of staining intensity and percentage positive
      cells) was quantified for the epithelial cytoplasmic (EC), epithelial nuclear
      (EN), and malignant stromal compartments. Multivariable Cox proportional hazard
      regression models were used to examine the relationship of IGF2 levels with
      progression-free survival (PFS) and overall survival (OS). Adjusting for stage,
      race, and adjuvant therapy, PFS and OS were reduced in patients with high IGF2 (H
      score >= median) in the EC and EN compartments. Black race was independently
      associated with reduced PFS and OS in patients with early-stage disease, and IGF2
      levels in the EC were higher in black than in white patients (P = 0.02, Wilcoxon
      test). In a race-stratified multivariable analysis, high IGF2 in the epithelial
      compartments more than doubled the risk of death in black women; HR = 2.43 (95%
      CI: 1.18-5.01, P = 0.02) for high IGF2 in the EC; and HR = 2.34 (95% CI: 1.25
      4.39, P = 0.008) for high IGF2 in the EN. In conclusion, high tumor IGF2
      expression is an independent risk factor for reduced PFS and OS in UCS. Black
      women have elevated tumor IGF2 compared with white women, and decreased survival
      associated with high IGF2. These findings identify IGF2 as a candidate biomarker
      for survival linked to racial disparity in women with UCS.

PMID- 29455467
TI  - Predicting reintroduction outcomes for highly vulnerable species that do not
      currently coexist with their key threats.
AB  - Predicting reintroduction outcomes before populations are released is inherently
      challenging. It becomes even more difficult when the species being considered for
      reintroduction no longer coexists with the key threats limiting its distribution.
      However, data from other species facing the same threats can be used to make
      predictions under these circumstances. We used an integrated Bayesian modeling
      approach to predict growth of a reintroduced population at a range of predator
      densities when no data are available for the species in the presence of that
      predator. North Island Saddlebacks (Philesturnus rufusater) were extirpated from
      mainland New Zealand by exotic mammalian predators, particularly ship rats (black
      rats [Rattus rattus]) but are now being considered for reintroduction to sites
      with intensive predator control. We initially modeled data from previous
      saddleback reintroductions to predator-free sites to predict population growth at
      a new predator-free site while accounting for random variation in vital rates
      among sites. We then predicted population growth at different rat-tracking rates
      (an index of rat density) by incorporating a previously modeled relationship
      between rat-tracking and vital rates of another predator-sensitive species, the
      North Island Robin (Petroica longipes), and accounted for greater vulnerability
      of saddlebacks to rat predation based on information on historical declines of
      both species. The results allowed population growth to be predicted as a function
      of management effort while accounting for uncertainty, which means formal
      decision analysis could be used to decide whether to proceed with a
      reintroduction. Similar approaches could be applied to other situations where
      data on the species of interest are limited and provide an alternative to
      decision making based solely on expert judgment.

PMID- 29455466
TI  - The effects of interleukin-33 on airways collagen deposition and matrix
      metalloproteinase expression in a murine surrogate of asthma.
AB  - It has been suggested that interleukin-33 (IL-33) plays an important role in the
      pathogenesis of asthma through a variety of pathways, but its role in airways
      fibrosis in asthma has not been fully elucidated. In the present study we
      evaluated changes in the expression of extracellular matrix proteins (ECMs) as
      well as matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in an IL-33
      induced, antigen-independent murine surrogate of asthma as well as a conventional
      surrogate employing per-nasal challenge of mice previously sensitized to produce
      an IgE response to ovalbumin (OVA). In addition, in in vitro experiments we
      explored the direct effects of IL-33 on the proliferation and function of murine
      fibroblasts. Per-nasal administration of IL-33 alone was sufficient to induce
      airways deposition of ECMs, including collagens I, III, V and fibronectin, to a
      degree comparable with that observed in the OVA-sensitized and challenged mice.
      These changes were associated with a local imbalance between the expression of
      extracellular MMPs and TIMPs. Per-nasal challenge of mice with IL-33 also induced
      elevated airways expression of connective tissue growth factor and fibroblast
      growth factor receptor 4, two key facilitators of local fibrosis, again to a
      degree compatible with that observed in OVA-sensitized and challenged mice.
      Deletion of the ST2 gene, which encodes the IL-33 receptor, abrogated these
      fibrotic changes in the airways in the OVA surrogate. In vitro, IL-33
      significantly increased the proliferation and expression of collagen III by
      murine lung fibroblasts. These data suggest that direct exposure of murine
      airways to IL-33 is able to induce local fibrotic changes, at least partially
      through effects of signalling through the IL-33/ST2 axis on fibroblast function
      and local expression of MMPs and their inhibitors, and other fibrosis-related
      proteins.

PMID- 29455469
TI  - Insect herbivory and plant adaptation in an early successional community.
AB  - To address the role of insect herbivores in adaptation of plant populations and
      the persistence of selection through succession, we manipulated herbivory in a
      long-term field experiment. We suppressed insects in half of 16 plots over nine
      years and examined the genotypic structure and chemical defense of common
      dandelion (Taraxacum officinale), a naturally colonizing perennial apomictic
      plant. Insect suppression doubled dandelion abundance in the first few years, but
      had negligible effects thereafter. Using microsatellite DNA markers, we genotyped
      >2500 plants and demonstrate that insect suppression altered the genotypic
      composition of plots in both sampling years. Phenotypic and genotypic estimates
      of defensive terpenes and phenolics from the field plots allowed us to infer
      phenotypic plasticity and the response of dandelion populations to insect
      mediated natural selection. The effects of insect suppression on plant chemistry
      were, indeed, driven both by plasticity and plant genotypic identity. In
      particular, di-phenolic inositol esters were more abundant in plots exposed to
      herbivory (due to the genotypic composition of the plots) and were also induced
      in response to herbivory. This field experiment thus demonstrates evolutionary
      sorting of plant genotypes in response to insect herbivores that was in same
      direction as the plastic defensive response within genotypes.

PMID- 29455468
TI  - Implications of macrophage polarization in autoimmunity.
AB  - Macrophages are extremely heterogeneous and plastic cells with an important role
      not only in physiological conditions, but also during inflammation (both for
      initiation and resolution). In the early 1990s, two different phenotypes of
      macrophages were described: one of them called classically activated (or
      inflammatory) macrophages (M1) and the other alternatively activated (or wound
      healing) macrophages (M2). Currently, it is known that functional polarization of
      macrophages into only two groups is an over-simplified description of macrophage
      heterogeneity and plasticity; indeed, it is necessary to consider a continuum of
      functional states. Overall, the current available data indicate that macrophage
      polarization is a multifactorial process in which a huge number of factors can be
      involved producing different activation scenarios. Once a macrophage adopts a
      phenotype, it still retains the ability to continue changing in response to new
      environmental influences. The reversibility of polarization has a critical
      therapeutic value, especially in diseases in which an M1/M2 imbalance plays a
      pathogenic role. In this review, we assess the high plasticity of macrophages and
      their potential to be exploited to reduce chronic/detrimental inflammation. On
      the whole, the evidence detailed in this review underscores macrophage
      polarization as a target of interest for immunotherapy.

PMID- 29455470
TI  - Separation of positional isomers of nine 2-phenethylamine-derived designer drugs
      by liquid chromatography-tandem mass spectrometry.
AB  - The synthesis of positional isomers of designer drugs is a common way of
      bypassing legal restrictions. For forensic case work, and especially for the
      legal assessment of cases, there is a need for screening methods capable of the
      unequivocal identification of positional isomers. The presented liquid
      chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS)
      method facilitates separation of positional isomers of 9 2-phenethylamine-derived
      designer drugs in different matrices including seized materials, hair, serum, and
      urine specimens. Chromatographic separation was achieved on a biphenyl phase
      using gradient elution with a total runtime of 26 minutes. The limit of detection
      was 25 pg/mg for hair samples and ranged from 0.1 ng/mL to 0.5 ng/mL for serum
      and from 0.2 ng/mL to 1.2 ng/mL for urine samples. The method proved to be
      selective and sensitive and showed good chromatographic resolution (R >= 1.2).
      The method was successfully applied to routine case samples.

PMID- 29455471
TI  - World traumatic dental injury prevalence and incidence, a meta-analysis-One
      billion living people have had traumatic dental injuries.
AB  - Traumatic dental injuries (TDIs) account for a considerable proportion of bodily
      injuries. Nevertheless, global TDI frequency is unknown, probably because TDI
      diagnosis is not standardized. This study estimated world TDI frequency. A
      literature search (publication years 1996-2016) was aimed at covering as many
      countries, communities, ethnic groups as possible, thus achieving high
      generalizability. In particular, non-specific keywords, no language restrictions,
      and large databanks were used. Observational studies reporting proportions of
      individuals with at least one TDI (prevalence) and who developed TDI (incidence
      rate) were considered. Prevalence rates to permanent dentition, primary dentition
      and in 12-year-olds, incidence rate to any tooth for any age, male-to-female
      prevalence ratio (PR) in 12-year-olds, with 95% confidence intervals (95 CIs),
      were extracted/calculated. Study quality, Z-score distribution, funnel plot
      symmetry analysis, between-study heterogeneity, sensitivity, and subgroup
      analyses were performed. Selected primary studies were 102 (permanent dentition;
      268 755 individuals; median age, 13.8 years), 46 (primary dentition; 59 436
      individuals; median age, 3.4 years), 42 (12-year-olds; 33 829 individuals), 11
      (incidence rate; 233 480 person-years; median age, 7.8 years), and 31 (PR; 16 003
      males, 16 006 females). World TDI frequency resulted as follows: permanent
      dentition prevalence 15.2% (95 CI, 13.0%-17.4%); primary dentition prevalence
      22.7% (95 CI, 17.3%-28.7%); 12-year-olds prevalence 18.1% (95 CI, 15.3%-21.0%);
      incidence rate, 2.82 (95 CI, 2.28%-3.42%) per 100 person-years; PR, 1.43 (95 CI,
      1.34%-1.52%). Differences between WHO Regions were found. This study shows that
      more than one billion living people have had TDI. TDI is a neglected condition
      which could rank fifth if it was included in the list of the world's most
      frequent acute/chronic diseases and injuries.

PMID- 29455472
TI  - Double-digest RAD sequencing outperforms microsatellite loci at assigning
      paternity and estimating relatedness: A proof of concept in a highly promiscuous
      bird.
AB  - Information on genetic relationships among individuals is essential to many
      studies of the behaviour and ecology of wild organisms. Parentage and relatedness
      assays based on large numbers of single nucleotide polymorphism (SNP) loci hold
      substantial advantages over the microsatellite markers traditionally used for
      these purposes. We present a double-digest restriction site-associated DNA
      sequencing (ddRAD-seq) analysis pipeline that, as such, simultaneously achieves
      the SNP discovery and genotyping steps and which is optimized to return a
      statistically powerful set of SNP markers (typically 150-600 after stringent
      filtering) from large numbers of individuals (up to 240 per run). We explore the
      trade-offs inherent in this approach through a set of experiments in a species
      with a complex social system, the variegated fairy-wren (Malurus lamberti) and
      further validate it in a phylogenetically broad set of other bird species.
      Through direct comparisons with a parallel data set from a robust panel of highly
      variable microsatellite markers, we show that this ddRAD-seq approach results in
      substantially improved power to discriminate among potential relatives and
      considerably more precise estimates of relatedness coefficients. The pipeline is
      designed to be universally applicable to all bird species (and with minor
      modifications to many other taxa), to be cost- and time-efficient, and to be
      replicable across independent runs such that genotype data from different study
      periods can be combined and analysed as field samples are accumulated.

PMID- 29455473
TI  - Comparison between magnetic resonance imaging, computed tomography, and
      arthrography to identify artificially induced cartilage defects of the equine
      carpal joints.
AB  - While articular cartilage changes are considered to be one of the initial events
      in the pathological cascade leading to osteoarthritis, these changes remain
      difficult to detect using conventional diagnostic imaging modalities such as
      plain radiography. The aim of this prospective, experimental, methods comparison
      study was to compare the sensitivity of magnetic resonance imaging (MRI),
      magnetic resonance arthrography, computed tomography (CT), and CT arthrography in
      the detection of artificially induced articular cartilage defects in the equine
      carpal joints. Defects were created in the antebrachiocarpal and middle carpal
      joint using curettage by a board-certified equine surgeon. Normal articular
      cartilage thickness varied from a maximum of 1.22 mm at the level of the distal
      aspect of the radius to a minimum of 0.17 mm in the proximal articular surface of
      the third carpal bone. Regarding cartilaginous defect measurements the remaining
      cartilaginous bed range from a maximum of 0.776 mm in the partial thickness
      defects, and 0 mm (defect reaches the subchondral bone) when total thickness
      defect were made. Computed tomography and magnetic resonance imaging were
      performed followed by CT arthrography and magnetic resonance arthrography after
      antebrachiocarpal and middle carpal intraarticular contrast administration. All
      images were reviewed by two board-certified veterinary radiologists, both of whom
      were blinded to the location, presence of, and thickness of the cartilage
      defects. A total number of 72 lesions in nine limbs were created. Mean
      sensitivity for localizing cartilage defects varied between imaging modalities
      with CT arthrography showing the best sensitivity (69.9%), followed by magnetic
      resonance arthrography (53.5%), MRI (33.3%), and CT (18.1%) respectively. The
      addition of contrast arthrography in both magnetic resonance and CT improved the
      rate of cartilage lesion detection although no statistical significance was
      found. Computed tomographic arthrography displayed the best sensitivity for
      detecting articular cartilage defects in the equine antebrachiocarpal and middle
      carpal joints, compared to magnetic resonance arthrography, MRI, and CT.

PMID- 29455474
TI  - Aging impacts CD103+ CD8+ T cell presence and induction by dendritic cells in the
      genital tract.
AB  - As women age, susceptibility to systemic and genital infections increases. Tissue
      resident memory T cells (TRMs) are CD103+ CD8+ long-lived lymphocytes that
      provide critical mucosal immune protection. Mucosal dendritic cells (DCs) are
      known to induce CD103 expression on CD8+ T cells. While CD103+ CD8+ T cells are
      found throughout the female reproductive tract (FRT), the extent to which aging
      impacts their presence and induction by DCs remains unknown. Using hysterectomy
      tissues, we found that endometrial CD103+ CD8+ T cells were increased in
      postmenopausal compared to premenopausal women. Endometrial DCs from
      postmenopausal women were significantly more effective at inducing CD103
      expression on allogeneic naive CD8+ T cells than DCs from premenopausal women;
      CD103 upregulation was mediated through membrane-bound TGFbeta signaling. In
      contrast, cervical CD103+ T cells and DC numbers declined in postmenopausal women
      with age. Decreases in DCs correlated with decreased CD103+ T cells in
      endocervix, but not ectocervix. Our findings demonstrate a previously
      unrecognized compartmentalization of TRMs in the FRT of postmenopausal women,
      with loss of TRMs and DCs in the cervix with aging, and increased TRMs and DC
      induction capacity in the endometrium. These findings are relevant to
      understanding immune protection in the FRT and to the design of vaccines for
      women of all ages.

PMID- 29455475
TI  - Nutrition education in the care of patients with chronic kidney disease and end
      stage renal disease.
AB  - Diet counseling and nutrition education are recommended in the prevention and
      management of chronic kidney disease (CKD) and end-stage renal disease (ESRD).
      The importance of effectively addressing nutrition with patients has grown given
      the increasing prevalence of obesity, hypertension, and diabetes; conditions
      which influence CKD/ESRD. Dietary advice for individuals with CKD/ESRD can be
      seen as complex; and successful dietary management requires careful planning,
      periodic assessment of nutritional status, as well as monitoring of dietary
      compliance. In spite of recommendations and pressing need, formal training in
      nutrition and adequate preparation for providers is limited; and for physicians
      the lack of nutrition education has been acknowledged, repeatedly, as an area for
      improvement in medical training curricula. It has also been suggested that
      dietitians have an essential role in management of CKD in the primary care
      setting; however, dietitians who do not practice renal education daily may need
      training on the specific challenges in CKD/ESRD. The objectives of this chapter
      were to: characterize select nutrition education resources for providers who care
      for patients with CKD/ESRD; summarize key dietary components emphasized in the
      care of patients with CKD/ESRD; and address practical considerations in
      educational efforts focused on nutrition and CKD/ESRD.

PMID- 29455476
TI  - [Emphasis on the importance of chemical drug treatment for spinal tuberculosis].

PMID- 29455477
TI  - [Application value of Xpert MTB/RIF in diagnosis of spinal tuberculosis and
      detection of rifampin resistance].
AB  - OBJECTIVE: To investigate the application value of Xpert MTB/RIF in diagnosis of
      spinal tuberculosis and detection of rifampin resistance. METHODS: The 109 pus
      specimens were obtained from patients who were primaryly diagnosed as spinal
      tuberculosis. All of the pus specimens were detected by acid-fast stain, liquid
      fast culturing by BACTEC MGIT 960 and Xpert MTB/RIF assay to definite the
      differences in sensitivity and specificity of mycobacterium tuberculosis among
      detecting methods. Pus specimens obtained by different methods were deteceded by
      MTB/RIF test to analyze the self-influence on Xpert MTB/RIF test. The result of
      liquid fast culturing by BACTEC MGIT 960 was used as the gold standard; and the
      value of Xpert MTB/RIF assay in detecting rifampin resistance was analyzed.
      RESULTS: The sensitivity of acid-fast stain, liquid fast culturing by BACTEC MGIT
      960 and Xpert MTB/RIF assay were 25.92%, 48.15%, 77.78%, respectively. The
      sensitivity of pus specimens obtained from open surgery, ultrasound positioning
      puncture and biopsy the sensitivity were 83.78%, 76.47%, 44.68% respectively
      deteceded by MTB/RIF test. According to the gold standard of the results of
      liquid fast culturing by BACTEC MGIT 960 assay, the sensitivity and specificity
      of Xpert MTB/RIF assay in detecting rifampin resistance were 80%(4/5) and
      90.70%(39/43), respectively. CONCLUSIONS: Xpert MTB/RIF assay has higher value in
      diagnosis of spinal tuberculosi, and also can detect rifampin resistance. The
      number of mycobacterium tuberculosis in pus specimens has a great influence in
      the sensitivity of Xpert MTB/RIF assay.

PMID- 29455478
TI  - [Comparision of clinical effects between one-stage anterior and posterior
      approach in treating thoracolumbar tuberculosis with debridement and internal
      fixation].
AB  - OBJECTIVE: To compare the outcomes of surgical operation by posterior or anterior
      approach only for thoracolumbar tuberculosis. METHODS: The clinical data of 97
      patients with thoracolumbar tuberculosis underwent debridement and internal
      fixation from January 2005 to December 2014 were retrospectively analyzed. The
      study included 59 males and 38 females, with a mean age of 53.7 years ranged from
      20 to 68 years. The course of disease was from 1 to 13 months with an average of
      (6.9+/-2.3) months. Among these patients, 43 cases were treated through one-stage
      anterior approach (anterior approach group) and 54 cases were treated through
      posterior approach (posterior approach group). The clinical data and imaging data
      of 97 cases were analyzed, including the operation time, intraoperative and
      postoperative blood loss, postoperative hospitalization time, complications,
      visual analogue scale(VAS), Oswestry Disability Index(ODI), Frankle grade, bone
      fusion time, and corrective rate of Cobb angle. RESULTS: Operation time,
      intraoperative and postoperative blood loss, postoperative hospitalization time,
      complication rate, and corrective rate of Cobb angle were(174.4+/-9.9) min,
      (885.0+/-95.7) ml, (103.2+/-11.5) ml, (15.1+/-0.7) d, 9.3%, (73.4+/-3.2)% in
      posterior group respectively, while in anterior approach group were(229.5+/-15.2)
      min, (1326.0+/-113.5) ml, (153.2+/-16.7) ml, (19.0+/-0.8) d, 16.3%, (62.3+/
      2.5)%, respectively, and there was significant difference between two groups.
      There was no significant difference in graft bone fusion between two groups.
      Postoperative VAS, ODI, Frankel grade of all patients were obviously improved,
      but there was no significant difference between two groups. CONCLUSIONS:
      Thoracolumbar tuberculosis could be cured by one-stage anterior or posterior
      approach with debridement, bone grafting and internal fixation, but posterior
      approach has advantages of less trauma and better deformity correction.

PMID- 29455479
TI  - [Clinical application of modified inverted L-shape incision by extraperitoneal
      approach to lumbosacral tuberculosis].
AB  - OBJECTIVE: To explore the clinical effects of one-stage posterior transpedicular
      screw system internal fixation combined with anterior debridement and bone
      grafting with modified inverted L-shape incision by extraperitoneal approach in
      treating multiple lumbosacral tuberculosis. METHODS: The clinical data of 15
      patients with multiple lumbosacral tuberculosis underwent operation from February
      2008 to December 2014 were retrospectively analyzed. There were 9 males and 6
      females with an average of (47.0+/-13.9) years old. The lesions involved L4-S1 in
      12 cases, L4-S2 in 1 case, L3-S1 in 2 cases. Five cases complicated with nerve
      root symptoms and 2 cases with cauda equina symptoms. All patients were treated
      with posterior transpedicular screw system internal fixation combined with
      anterior L4,5, L5S1 debridement and bone grafting with modified inverted L-shape
      incision by extraperitoneal approach. Operation time, blood loss, incision
      length, first passage of gas by anus were recorded. The condition of bone fusion
      and focus absorption were observed by lumbar CT and MRI; and ESR and CRP were
      regularly rechecked. RESULTS: Fifteen patients were followed up for 18-24 months
      with an average of (20.0+/-2.73) months. All lumbosacral pain obtained
      improvement, and no hardware loosening, breaking, or bone graft block loosening
      was found. The operative time of anterior-posterior approach surgery was 210-250
      min with an average of (231.0+/-12.1) min; the blood loss was 320-705 ml with an
      average of(495.0+/-130.3) ml; the incision length was 15-21 cm with an average of
      (16.4+/-3.4) cm, and the extended length of inverted L-shape incision was 6 to 9
      cm with an average of (7.1+/-2.6) cm. The time of first passage of gas by anus
      was 14 to 40 h with an average of (24.1+/-7.4) h after operation. All bone graft
      obtained fusion at final follow-up, and spinal cord symptoms got recovery, ESR
      and CRP restored normal level with no recurred at 3 months after drug withdrawal.
      CONCLUSIONS: The treatment of multiple lumbosacral tuberculosis with posterior
      transpedicular screw system internal fixation combined with anterior debridement
      and bone fusion with modified inverted L-shape incision by extraperitoneal
      approach is feasible and practical. This method has advantages of little trauma,
      good exposure, less complications and high security.

PMID- 29455480
TI  - [Application of guide combined with probing the internal wall of pedicle screw
      trajectory for subaxial cervical pedicle screw placement].
AB  - OBJECTIVE: To investigate the skill and evaluate the accuracy for application of
      guide combined with probing the internal wall of pedicle screw trajectory for
      subaxial cervical pedicle screw placement. METHODS: Subaxial cervical pedicle
      screw was inserted in 11 patients by the guide combined with probing the internal
      wall of pedicle screw trajectory from January 2014 to October 2016, including 7
      males and 4 females with an average age of 48.1 years(ranged 32 to 63 years).
      There were 4 cases with cervical spondylotic myelopathy, 4 with fracture and
      dislocation of cervical vertebrae, 1 with cervical cord injury without fracture
      and dislocation, and 2 with atlantoaxialfracture and dislocation. The target
      pedicle's diameter, optimal entry point, sagittal angle and cross-sectional angle
      were measured by CT before operation. During operation, the pedicle screw
      inserted angle was controlled by a guide with a self-designed protractor and
      probed the internal wall of pedicle screw trajectory as medial safety margin of
      insertion screw. The accuracy of cervical pedicle screw was evaluated by CT with
      classification of four grades and assessed whether there was injury of spine cord
      or vertebral artery postoperatively. RESULTS: Seventy-one cervical pedicle screws
      were placed among 11 patients, and no one had been found with clinical
      manifestations of injury of spine cord (or nerve root) or vertebral artery after
      operation. According to postoperative CT scan for evaluating the grade of screw
      position, 52 screws were in grade 0, 13 in grade 1, 4 in grade 2, 2 in grade 3,
      and 91% (65/71) located in good position. In total, 6 screws were incorreted in
      placement, and 4 cases of them broke medial wall and 2 cases broke lateral wall.
      CONCLUSIONS: The method of probing the internal wall of pedicle screw trajectory
      for subaxial cervical pedicle screw placement is safe and reliable, but the
      studying curve is long. Probing the internal wall of pedicle screw trajectory and
      controlling the insertion angle by guide with a protractor are key points of this
      technology.

PMID- 29455481
TI  - [Mid-term follow-up and coping strategies of bone cement leakage after
      percutaneous kyphoplasty].
AB  - OBJECTIVE: To retrospectively analyze the clinical data of 17 patients with bone
      cement leakage after percutaneous kyphoplasty and explore the leakage type and
      mid-term clinical effects. METHODS: The clinical data of 17 patients with
      osteoporotic vertebral compression fractures occurred bone cement leakage after
      percutaneous kyphoplasty from October 2011 to October 2016 were collected. There
      were 7 males and 10 females, aged from 68 to 87 years old with an average of 78
      years. All the patients had the history of low emergy trauma who had normal
      activity and full self-care for living before trauma, and complained with the
      lower back pain without signs and symptoms of nerve root injury after trauma.
      According to the anatomical location by images, the bone cement leakage pathways
      was confirmed, the preoperative and postoperative vertebral body height and Cobb
      angle were measured, the improvement of spinal stenosis were recorded.
      Preoperative and postoperative visual analogue scale (VAS) and Oswestry
      Disability Index(ODI) were used to evaluate pain and daily activities. RESULTS:
      All the patients were followed up for 4 to 7 years with an average of 5.1 years.
      According to anatomical location by images, we found the bone cement leakage
      pathways of vertebral side type in 6 cases, intervertebral disc type in 3 cases,
      spinal canal type in 2 cases, vertebral pedicle type in 5 cases and mixed type in
      1 case. Vertebral body height from preoperative(27.7+/-3.5)% restored to (56.4+/
      2.5)% at final follow-up, and the kyphosis was corrected with Cobb angle from
      preoperative(45.3+/-4.2) degrees  corrected to(18.3+/-3.1) degrees  at final
      follow-up. VAS score decreased from preoperative 7.9+/-1.5 to 2.1+/-0.5 at final
      follow-up. ODI obviously restored from preoperative(49.1+/-7.5)% to (23.5+/-3.7)%
      at final follow-up. The nerve symptoms in lower limbs occurred in 2 cases, and
      the neurological symptom was disappeared after urgent symptomatic treatment and
      anaphase trophic nerve treating. Lower back pain occurred in 3 cases, including
      one case of unbearable pain, and the pain disappeared after symptomatic
      treatment. CONCLUSIONS: Although the rate of bone cement leakage during
      percutaneous vertebral kyphoplasty is not low, the bone cement leakage has little
      influence on PKP surgery. Even if a little leakage occurred within the spinal
      canal during the surgery, spinal canal decompression will not be needed urgently.
      The significant clinical symptoms caused by leakage can basically disappear after
      treatment in mid-term follow-up.

PMID- 29455482
TI  - [Clinical efficacy of unilateral percutaneous transfacet screws combined with
      contralateral pedicle screw versus bilateral pedicle screws fixation in the
      treatment of the degenerative lumbar disease].
AB  - OBJECTIVE: To investigate the surgical outcome of unilateral pedicle screw(UPS)
      after TLIF technique combined with contralateral percutaneous transfacet
      screw(PTS) fixation vs bilateral pedicle screws(BPS) fixation in treatment of
      degenerative lumbar disease. METHODS: From January 2009 to June 2012, 46 patients
      with degenerative lumbar diseases, including 30 males and 16 females with an
      average age of 51.5 years old, who were divided into two groups according to
      different fixation methods. Twenty-two cases underwent UPS after TLIF technique
      combined with contralateral PTS fixation (group A), while the others underwent
      BPS fixation(group B). The relative data were analyzed, such as blood loss
      volume, operative time, fusion rate, ODI score, JOA score and so on. RESULTS: All
      the patients were followed up for 1 to 3 years with an average of 22 months.
      Except one case of each group was uncertainty fusion, the rest have obtained bony
      fusion, and the fusion rates in group A and B were 95.5% and 95.8%, respectively.
      No displacement and breakage of screw were found during follow-up. Operative time
      and blood loss volume in group A were better than of group B(P<0.05). ODI and JOA
      scores had improved obviously than preoperation(P<0.05), but the differences had
      no statistical significance between two groups(P>0.05). CONCLUSIONS: Two
      approaches had similar clinical outcomes for degenerative lumbar disease with no
      severe instability. Compared with BPS fixation, the UPS after TLIF technique and
      contralateral PTS fixation has the advantages of less trauma, shorter operative
      time and less blood loss, and it is a safe and feasible surgical technique.

PMID- 29455483
TI  - [Analysis of clinical outcome of kyphoplasty on costal pain related to thoracic
      osteoporotic compression fractures].
AB  - OBJECTIVE: To analyze the clinical outcome of kyphoplasty on costal pain which
      develops following thoracic osteoporotic compression fractures and evaluate the
      factors related to costal pain. METHODS: From May 2014 to May 2016, a total of
      188 patients with thoracic osteoporotic compression fractures undergoing
      kyphoplasty were reviewed retrospectively. The patients were divided into two
      groups: the costal pain group included patients who had costal pain after a
      vertebral fracture and the no costal pain group included patients without
      costalgia. Visual analogue scale(VAS)and Oswestry Disability Index(ODI)of all
      patients were measured preoperatively and 3 days, 1 month, 6 months
      postoperatively respectively. Gender, age, the fracture level, bone mineral
      density, vertebral body fracture type, and fracture severity were compared
      between two groups, and the causes of costal pain were analyzed. RESULTS: Among
      188 patients, 38 patients (20.2%) complained of costal pain with back pain. The
      mean follow-up time was 8.3 months (ranged from 6 to 15 months). The VAS and ODI
      score of two groups decreased after operation, and there was significant
      difference between pre-operation and post-operation(P<0.05). There was
      significant difference in VAS score and ODI score between two groups at 3 days
      and 1 month postoperatively (P<0.05). There was no significant difference in VAS
      score and ODI score between two groups at 6 months postoperatively (P<0.05). The
      incidence of applanation-type deformity and severe fracture in the costal group
      were higher. The fracture type and fracture severity showed significantly
      difference between two groups(P<0.05). CONCLUSIONS: The fracture type and
      fracture severity had significant relation to costal pain of thoracic
      osteoporotic compression fractures. The kyphoplasty effect on costal pain may not
      be effective, especially during early post-operation period.

PMID- 29455484
TI  - [Analysis of clinical outcomes of simplified treatment of lumbar
      spondylolisthesis with adjacent segment degeneration by MAST Quadrant].
AB  - OBJECTIVE: To explore the method and clinical effect of MAST Quadrant for lumbar
      spondylolisthesis with adjacent segment degeneration. METHODS: From April 2014 to
      January 2016, 36 cases of lumbar spondylolisthesis with adjacent segment
      degeneration were treated by MAST Quadrant(target nerve decompression and
      transforaminal lumbar interbody fusion or articulationes zygapophysiales fusion
      by unilateral fixation with MAST Quadrant). Twenty-three cases were degenerative
      lumbar spondylolisthesis and 13 cases were isthmic lumbar spondylolisthesis.
      According to Meyerding grade of spondylolisthesis, 16 cases were grade I, 17
      cases were grade II, and 3 cases were grade III. Visual analogue score (VAS),
      Oswesty Disability Index (ODI) and JOA score were used to evaluate the clinical
      outcome. RESULTS: The amount of intraoperative bleeding was 230 to 480 ml with an
      average of 340 ml and the amount of postoperative blood loss was 15 to 80 ml with
      an average of 43 ml. Operative time was 176 to 240 min with an average of 193
      min; X-ray exposure time was 2 to 6 s with an average of 3.6 s. Two cases were
      complicated with dural tear without nerve injury during operation. Thirty cases
      were followed up from 12 to 17 months with an average of 15.2 months. VAS scores
      for preoperative, 5 days, 3 months after surgery were 7.6+/-1.7, 1.9+/-0.4, 0.8+/
      0.4 respectively, and there was significant difference before and after
      operation(P<0.05). The ODI scores for preoperative and 3 months after surgery
      were 35.9+/-1.2 and 3.7+/-0.7 respectively, and there was significant difference
      before and after operation(P<0.05). JOA scores for preoperative, 5 days, 1
      months, 3 months after surgery were 13.2+/-0.4, 24.4+/-0.4, 27.4+/-0.1, 27.9+/
      0.5 respectively, and there was significant difference before and after
      operation(P<0.05). CONCLUSIONS: MAST Quadrant can be applied to treat lumbar
      spondylolisthesis with adjacent segment degeneration, and the minimally invasive
      sugical technique is a safe and effective method, with the advantage of simple
      operation, fast recovery.

PMID- 29455485
TI  - [Risk factors of non-surgical vertebral fracture after percutaneous kyphoplasty
      of single segment thoracolumbar fracture].
AB  - OBJECTIVE: To investigate the risk factors of non-surgical vertebral fracture
      after percutaneous kyphoplasty (PKP) in patients with single segment
      thoracolumbar osteoporotic vertebral compression fracture(OVCF). METHODS: The
      clinical data of 219 patients with single segment thoracolumbar osteoporotic
      vertebral compression fracture underwent percutaneous kyphoplasty from January
      2010 to December 2015 were retrospectively analyzed. There were 29 cases in non
      surgical vertebral body fracture group with 7 males and 22 females aged (67.35+/
      9.92) years. Bone mineral density was(-3.89+/-0.72)SD, fracture compressed degree
      was (0.57+/-0.35)%, bone cement injected volume was (4.53+/-1.64) ml, and
      vertebral height recovery was (0.49+/-0.86)% on average. Ten cases were with
      vertebral body space fracture, 7 cases with bone cement leakage to the
      intervertebral disc, 9 cases with bone cement leakage to the peripheral tissue
      and 14 cases were treated by systemic anti-osteoporosis treatment after
      operation. Other 190 cases in non-surgical vertebral body without fracture group,
      and there were 42 males and 148 females, aged (66.98+/-7.55) years. Bone mineral
      density was (-3.13+/-0.59) SD, fracture compressed degree was (0.39+/-0.60)%,
      bone cement injected volume was (4.72+/-1.28) ml, and vertebral height recovery
      was (0.46+/-0.94)% on average. Among them, 13 cases were with vertebral body
      space fracture, 5 cases with bone cement leakage to the intervertebral disc, 29
      cases with bone cement leakage to the peripheral tissue and 129 cases were
      treated by systemic anti-osteoporosis treatment after operation. The factors of
      gender, age, fracture compressed degree, fractured type, bone mineral density,
      bone cement injected volume, bone cement leakage, vertebral height recovery,
      adjacent vertebral fractures, and systemic anti-osteoporosis treatment were
      studied in the two groups for single factor analysis. For the results with
      significant differences among above factors, the multivariate logistic regression
      analysis was used to research the non-surgical vertebral fracture risk factors.
      RESULTS: Among the 219 patients with single thoracolumbar fractures, 29 cases
      occurred non-surgical vertebral fractures. The single factor analysis results
      showed that there was no significant correlation between non-surgical vertebral
      fracture occurrecne with age, sex, fracture compressed degree, bone cement
      injected volume, and vertebral height recovery(P>0.05), but there was a
      significant correlation between non-surgical vertebral fracture occurrence with
      fractured type, bone cement leakage, systemic anti-osteoporosis treatment, and
      bone mineral density (P<0.05). Multivariate logistic regression analysis showed
      that fractured type(OR=0.135), whether systemic anti-osteoporosis treatment
      (OR=3.793), bone cement leakage (OR=8.975), and bone density (OR=57.079) are risk
      factors for postoperative non-surgical vertebral fractures. CONCLUSIONS:
      Improving the quality of the people, systemic preventing and treating the
      osteoporosis, improving the surgical skills and decreasing the bone cement
      leakage during operation are effective methods to prevent postoperative non
      surgical vertebral fractures.

PMID- 29455486
TI  - [Anterior cervical hybrid surgical treatment for multilevel cervical spondylotic
      myelopathy].
AB  - OBJECTIVE: To evaluate the clinical results of anterior cervical discectomy and
      reconstruction with a self-locking cage and internal fixation with short
      segmental plate for multilevel cervical spondylotic myelopathy. METHODS: From
      January 2012 to June 2015, a total of 106 patients received anterior cervical
      discectomy and reconstruction with a self-locking cage and internal fixation with
      short segmental plate were followed up. There were 71 males and 35 females, aged
      from 42 to 74 years old with an average of(55.4+/-5.1) years. Three segments were
      involved in 82 cases and four segments in 24 cases. Operation time, blood loss,
      postoperative drainage, and hospitalization time were recorded. Visual analogue
      scale(VAS) and Japanese Orthopaedic Association Score (JOA) were analyzed before
      and after operation(including 5 days, 3, 6, 12 months after operation and final
      follow-up), and the JOA improvement rate was analyzed. The cervical lordosis and
      ROM were measured before and after operation(including the follow-up point above)
      by X-rays. The postoperative complications were recorded and analyzed as well.
      RESULTS: All the operations were successful. The average operative time was
      (126.2+/-25.1) min, and the amount of blood loss was (82.1+/-26.3) ml. All the
      patients were followed up from 12 to 48 months with an average of (30.4+/-10.5)
      months. The VAS score of neck pain and JOA score was significantly better from
      6.11+/-1.54 and 9.22+/-2.42 preoperatively to 2.14+/-0.51 and 12.46+/-1.42 at 5
      days post-operation, respectively(P<0.05). The improvement rate of JOA was
      (56.7+/-21.6)%, there was no statistically significant difference of VAS, JOA
      scores and the improvement rate of JOA at each time after operation (P>0.05).
      Postoperative cervical lordosis at 3 months was significantly improved from
      preoperative (11.5+/-6.8) degrees  to (19.6+/-8.9) degrees (P<0.05), and it can
      keep satisfactory stability until final follow-up(P>0.05). Postoperative ROM at 3
      months was significantly decreased from the preoperative (37.6+/-10.4) degrees 
      to (18.2+/-5.9) degrees (P<0.05), but there was no significant change in the
      process of follow-up (P>0.05). All the complications such as dysphagia (19
      cases), axial neck pain(6 cases), cerebral fluid leakage(3 cases), and
      hoarseness(2 cases), got better after conservative treatment. Three cases had
      intervertebral space non-fusion until final follow-up(without clinical symptom),
      but no loosening, breakage, or displacement of internal fixation were found.
      CONCLUSIONS: Anterior cervical discectomy, reconstruction with a self-locking
      cage and internal fixation with short segmental plate which can reduce
      intraoperative injury, restore cervical lordosis, improve neurological function
      and lower postoperative complications, it is an alternative treatment for
      multilevel cervical spondylotic myelopathy.

PMID- 29455487
TI  - [French door segmented laminectomy decompression for severe cervical ossification
      of posterior longitudinal ligament complicated with spinal cord injury].
AB  - OBJECTIVE: To evaluate the clinical effects of French door segmented laminectomy
      decompression for severe cervical OPLL complicated with spinal cord injury.
      METHODS: The clinical data of 38 patients with serious cervical OPLL complicated
      with spinal cord injury were retrospectively analyzed and these patients were
      treated with French door segmented laminectomy decompression and internal
      fixation from June 2012 to June 2014. There were 25 males and 13 females, aged
      from 42 to 78 years with an average of 58.2 years. Of them, 35 cases suffered
      from aggravating neurological symptoms with a definite precipitating factor.
      Spinal cord injury was related to minor injury of the neck, such as
      hyperextension of the neck in 3 cases. Preoperative Japanese Orthopaedic Score
      (JOA) was 8.1+/-1.7 and Neck Disability Index (NDI) was 19.8+/-4.4. Preoperative
      CT scans showed the range of OPLL was more than three segments. The spinal canal
      was occupied 50% to 85% with an average of 70.7%. RESULTS: All the patients were
      followed up for 10 to 24 months with an average of 15.6 months. The operative
      time was 90 to 150 min with an average of 120 min and blood loss was 300 to 800
      ml with an average of (480+/-80) ml. At final follow-up, NDI and JOA were 7.5+/
      2.5 and 13.5+/-2.0, respectively, and they were obviously improved compared with
      preoperation. Preoperative cervical Cobb angle was (8.10+/-2.70) degrees  and at
      final follow-up was (15.60+/-1.80) degrees , and there was significant difference
      between preoperative and postoperative (P<0.05). Deep infection occurred in 1
      case, epidural hematoma in 1 case, C5 nerve root palsy in 3 cases, and axial
      symptom in 8 cases after operation. No serious complications, such as vertebral
      artery injury, cerebrospinal fluid leakage, deterioration of neurological
      dysfunction, or internal fixation failure was found. CONCLUSIONS: French door
      segmented laminectomy decompression is safe and feasible for severe cervical OPLL
      complicated with spinal cord injury, and it is worth to be popularized in future.

PMID- 29455488
TI  - [Analysis of clinical effects of absorbable hemostatic fluid gelatin and
      absorbable gelatin sponge on the hemostasis during operation of unilateral open
      door cervical expansive laminoplasty].
AB  - OBJECTIVE: To compare the hemostatic effect between absorbable hemostatic fluid
      gelatin (HFG) and absorbable gelatin sponge(GS) during operation of unilateral
      open-door cervical expansive laminoplasty. METHODS: The clinical data of 83
      patients underwent unilateral open-door cervical expansive laminoplasty from
      February 2014 to May 2016 were retrospectively analyzed. According to the used
      hemostatic materials, patients were divided into two groups. In HFG group, there
      were 30 males and 11 females, ranging in age from 29 to 81 years, with an average
      of(55.6+/-11.6)years; 14 cases were simple cervical spinal stenosis, 9 were
      cervical spinal stenosis and ossification of posterior longitudinal ligament, and
      18 were cervical spinal stenosis complicated with multiple cervical disc
      herniation. And in GS group, there were 32 males and 10 females, ranging in age
      from 36 to 78 years, with an average of (55.4+/-11.1) years; 12 cases were simple
      cervical spinal stenosis, 10 were cervical spinal stenosis complicated with
      ossification of posterior longitudinal ligament, and 20 were cervical spinal
      stenosis complicated with multiple cervical disc herniation. There was no
      significant difference in the age, gender, and disease categories of patients
      between two groups (P>0.05). The operative time, intraoperative bleeding,
      postoperative drainage, and postoperative complications were compared between two
      groups. RESULTS: The average operative time, intraoperative bleeding, and
      postoperative drainage in HFG group were(137.2+/-30.0) min, (156.1+/-74.6) ml,
      and (212.1+/-67.6) ml, respectively; and in GS group were (154.8+/-33.5) min,
      (242.9+/-120.7) ml, and(303.3+/-115.5) ml, respectively. There were significantly
      differences in above items between two groups(P<0.05). No acute heamatoma or
      related complications was found postoperatively. CONCLUSIONS: Compared with GS,
      HFG can obviously decrease operative time, intraoperative bleeding, and
      postoperative drainage. It is a safe and effective hemostatic material for the
      operation of unilateral open-door cervical expansive laminoplasty.

PMID- 29455489
TI  - [Causes prevention and treatment for cerebrospinal leak after lumbar revision
      surgery].
AB  - OBJECTIVE: To analyze the causes and explore the measures of prevention and
      treatment of the cerebrospinal leak after lumbar revision surgery. METHODS: The
      clinical data of 24 patients(17.78%) with cerebrospinal leak among 135 cases
      after lumbar revision surgery from January 2011 to January 2016 was
      retrospectively studied. Of them, 12 cases due to severe adhesion caused by scar
      formation; 4 cases due to yellow ligament hyperplasia adhesion with dura mater
      occurred dural tears when separating adhesion; 2 cases with severe hyperplasia
      and ossification of lumbar posterior longitudinal ligament occurred dural tears
      when revealing intervertebral disk; 2 cases due to improper nailing happened
      dural tears during operation. And the other 4 cases without obvious dural tears
      in surgery, occurred cerebrospinal leak one to two days after surgery. And the 24
      patients were treated with the measures of prevention and treatment
      preoperatively, intraoperatively, and postoperatively. RESULTS: Twenty-four
      patients with cerebrospinal leak were cured after treatment and were follow-up
      for 6 to 30 months. No recurrence of cerebrospinal leake or local and systemic
      complications were found. CONCLUSIONS: Scar formation is the main cause of
      cerebrospinal leak in lumbar revision surgery. As for lumbar revision surgery, as
      long as the standard control measures are taken, it can significantly reduce the
      incidence of cerebrospinal leak, achieve better clinical efficacy, and
      fundamentally solve the cerebrospinal leak problem that has plagued both doctors
      and patients for a long time.

PMID- 29455490
TI  - [Clinical application of anterior thoracoscopically assisted surgery with
      posterior one-stage total en block spondylectomy for thoracic spinal tumor].
AB  - OBJECTIVE: To investigate the clincial effects and feasibility of anterior
      thoracoscopically assisted surgery (TAS) with posterior one-stage total en block
      spondylectomy(TES) for thoracic spinal tumour. METHODS: From October 2014 to
      January 2016, 4 patients with thoracic spinal tumour were treated by anterior
      thoracoscopically assisted surgery with posterior one-stage total en block
      spondylectomy. There were 2 males and 2 females, aged 16, 35, 46, 60 years.
      Courses of disease were 1, 4, 6, 9 months. The tumor occurred at T4, T6, T130
      segment in 1 case respectively, at double T7/T8 segments in 1 case. Preoperative
      visual analogue scores(VAS) were 4, 5, 6, 8 points. Frankel grade of neurologic
      function was grade B in 2, D in 1, and E in 1. SF-36 quality of life scores were
      38, 65, 35, 29 points, including 2 cases of primary spinal tumors, 2 cases of
      metastatic spinal tumors. According to the classification of Tomita, 1 case was
      type III, 2 cases were type IV, 1 case was type VI. And according to the WBB
      staging, 4-9/ABCD was in 2 cases, 5-8/ABC compliated with 1-3 was in 1 case, 6
      7/ABC was in 1 case. Surgical procedure: With lateral position, the thoracoscope
      channel was inserted. The involved intervertebral vessels and corresponding
      intercostal vessels were ligated, while the prevertebral large vessels were
      completely separated and protected. The front halves of superior and inferior
      involved vertebral discs were removed. Then the patients were changed to prone
      position, posterior one-stage total en block spondylectomy, titanium cage bone
      graft (allograft bone), pedicle screw fixation were performed. RESULTS: All of
      the operations were successful and the patients were followed up for 34, 10, 11,
      12 months. Pleural effusion occurred in 1 case after operation, and pleural
      closed drainage was done. All incisions got primary healing; and all patients
      showed significant pain relief (P<0.005), with the VAS score decreasing to 2(2
      cases) and 3(2 cases) scores, 2 months after surgery. No nerve functional injury
      aggravated. SF-36 quality of life score obviously improved with postoperative
      scores for 88, 92, 71, 80 at 3 months after operation. No recurrent vertebral
      tumor, internal fixation lossening or breakage was found at follow-up points of
      3, 6, 12 months. One patient with lung cancer died of multiple organ failure at
      11 months after operation. CONCLUSIONS: With anterior TAS, vertebral anterior
      vessels, intervertebral blood vessels, intercostal vessels were successfully
      separated or ligated, intraoperative bleeding was effectively controlled, lung
      and esophagus were effectively protected, and the tumor received wide excision.
      Anterior TAS and one-stage posterior TES could significantly reduce the surgical
      trauma and the risk of surgery.

PMID- 29455491
TI  - [Percataneous endoscopic lumbar discectomy for the treatment of lumbar
      intervertebral disc protrusion].
AB  - OBJECTIVE: To explore the clinical effects of percataneous endoscopic lumbar
      discectomy for lumbar intervertebral disc protrusion. METHODS: The clinical data
      of 46 patients with lumbar intervertebral disc protrusion underwent percataneous
      endoscopic lumbar discectomy were retrospectively analyzed. There were 21 males
      and 25 females, aged from 23 to 65 years old with an average of 42 years. The
      course of disease was from 5 to 87 months with an average of 13.4 months.
      Protrusion located in L2,3 of 2 cases, L3,4 of 3 cases, L4,5 of 28 cases, L5S1 of
      13 cases. There were 5 patients with central type, 34 with para-side type, 7 with
      extreme lateral type. VAS, ODI and JOA scores were used to analyze the condition
      of pain releasing and lumbar functional improvement. According to MacNab standard
      to evaluate the clinical effect at final follow-up. RESULTS: All the operations
      were successful, operative time was 125 to 210 min with a mean of 153.6 min; and
      all the patients were follow-up for 6 to 12 months with an average of 8 months;
      no injuries of nerve and blood vessel, infection were found. Postoperative 3 days
      and final follow-up, VAS score was 3.1+/-0.7, 2.2+/-0.6 respectively, and was
      obviously lower than preoperative 7.3+/-1.2(P<0.05). At final follow-up, JOA and
      ODI were (23.5+/-2.4) points, and (22.10+/-9.26)%, respectively, and was
      obviously improved compared with preoperative (13.2+/-2.8) points and (69.12+/
      13.15)% (P<0.05). According to modified MacNab standard to evaluate the clinical
      outcome, 30 cases got excellent results, 14 good, 2 fair, no recurred and
      overhauling were found. CONCLUSIONS: Percataneous endoscopic lumbar discectomy is
      a minimally invasive technique, with advantage of safety and effectiveness, and
      apply to treatment of lumbar intervertebral disc protrusion.

PMID- 29455492
TI  - [Relationship between inflammatory cytokines of IL-1beta and TNF-alpha and
      intervertebral disc degeneration].
AB  - The inflammatory cytokines of IL-1beta and TNF-alpha participate in the process
      of intervertebral disc degeneration is focused by the spine surgeons.
      Inflammatory cytokines represented by IL-1beta and TNF-alpha act as the key
      factors in the process of intervertebral disc degeneration resulting in low back
      pain and radicular symptoms. Annulus fibrosus and nucleus pulposus can secrete
      TNF-alpha and IL-1beta under the stimulation of mechanical injury, overstressed,
      genetic susceptibility and infection. The mechanism of inflammatory cytokines in
      intervertebral disc degeneration needs further investigation. The emphasis of
      researches will be on the inflammatory cytokines in the regulation of mechanism
      in the intervertebral disc degeneration, molecular targeted therapy, cell
      signaling pathways and the best time of anti-inflammatory therapy providing more
      evidence in the clinical application.

PMID- 29455493
TI  - [Classification of upper cervical fractures: a review].
AB  - Upper cervical fracture-dislocations are series of pathological injuries occurred
      in occipital, atlas and axis caused by traumatic impact, which often results in
      severe clinical consequences, such as paraplegia, quadriplegia, and even death.
      In light of the potential severe clinical outcomes, it is important to define the
      type of upper cervical fracture-dislocations depending on which the clinician can
      deal with the disease properly. Owing to its specific anatomical structures, the
      upper cervical fractures occurr to the unique osseous structures or ligamentous
      connections always present in predictable patterns. Common fracture include
      occipital condylar fracture, atlanto-occipital dislocation, atlas fracture, and
      the three types of fractures of axis, including odontoid fracture, Hangman's
      fracture and axis body fracture. In this paper we will review the literatures
      about the classification and management of upper cervical fracture, to help the
      clinicians to treat their patients better.

PMID- 29455494
TI  - [Progress on diagnosis and treatment of tophus].
AB  - Tophi deposit in the peripheral bone joints or soft tissues are formed by uric
      acid and urate crystal. It does not only affect local appearance but also destroy
      the bone and joint structure, resulting in loss of function. Traditional medical
      treatment is an effective way to control the hyperuricemia, but it is ineffective
      to tophus. Surgery is a relatively effective method for the treatment of tophus.
      It can successfully reduces the content of uric acid in the body and improves the
      limbs function, but it causes surgical trauma and complications. As new medicine,
      Urcase is a hot spot in the present study. It can not only control the blood uric
      acid level but also dissolve part of tophus. But the cost is higher than
      traditional medicines. There is still dispute in treatment for advanced tophus.

PMID- 29455495
TI  - [Recent advances on the application and research of shoulder arthroscopy].

PMID- 29455496
TI  - [Comparison of therapeutic effects of three repair methods for rotator cuff tears
      under arthroscopy].
AB  - OBJECTIVE: To retrospectively study curative effects of three repair methods for
      rotator cuff tears under arthroscopy, and to explore relationships between
      different repair methods and cuff lesions. METHODS: From January 2009 to Jaunary
      2014, a total of 353 patients with rotator cuff tears treated with surgical
      repair under arthroscopy were included in this study. All the patients were
      divided into three groups according to time of visitiny hospital and it was
      divided into three periods. The patients on the first period were treated with
      single row rivet fixation(115 cases), including 51 males and 64 females, with an
      average age of (57.46+/-9.08) years old. The patients on the second period were
      treated with double row rivet fixation(163 cases), including 76 males and 87
      females, with an average age of (56.93+/-9.92) years old. The patients in the
      third period were treated with suture bridge fixation(75 cases), including 32
      males and 43 females, with an average age of (55.90+/-9.15) years old. There were
      29 patients with huge rotator cuff injuries, who were treated with single-row
      suture. The shoulders were protected by a brace for 6 weeks after operations were
      permit ted to perform passive movement within 6 weeks, and then perform active
      shoulder exercise 6 to 10 weeks after operation. Constant-Murley score, UCLA
      score and VAS score were recorded preoperatively and postoperatively. RESULTS:
      All the patients were followed up, and the duration ranged from 12 to 62 months,
      with a mean of 30 months. There was no infection or nerve injury. UCLA score was
      improved from preoperative 10.71+/-2.45 to postoperative 32.07+/-3.16; Constant
      Murley score was improved from preoperative 43.33+/-11.55 to postoperative
      78.15+/-12.64; VAS score was improved from preoperative 5.81+/-1.27 to
      postoperative 0.52+/-0.71. There were no statistical differences among three
      groups in UCLA score, Constant-Murley score and VAS score. Total 337 cases were
      satisfied with treatment results and 16 cases were not satisfied with the
      results. Among the 16 cases, 3 cases had huge rotator cuff surgery, and 13 cases
      had no joint stiffness before operation. The main complaints that resulted in
      dissatisfaction were weakness of the postoperative muscles and failure to restore
      the labour capacity(11 cases). CONCLUSIONS: Rotator cuff repair under arthroscopy
      has a reliable clinical effect for the patients with rotator cuff tears. Stable
      and reliable clinical results can be obtained regardless different repair methods
      or different rotator cuff tears. The following factors such as no stiffness
      before operation, too early active exercise and preoperative rotator cuff atrophy
      may be the risk factors for postoperative dissatisfaction of patients.

PMID- 29455497
TI  - [Clinical research of treating the avulsed fracture of humerus greater tuberosity
      using an arthroscopic double-row suture anchor fixation technique].
AB  - OBJECTIVE: To evaluate the early clinical effects of treating the avulsed
      fracture of humerus greater tuberosity using the double-row suture anchor
      fixation technique. METHODS: Total 20 patients with the avulsed fracture of the
      greater tuberosity of the humerus were treated from September 2009 to January
      2013. There were 12 males and 7 females, with an average age of 46.8 years old(24
      to 69 years old). Eleven patients had injuries on right shoulder joint and 8
      patients had injuries on left side. The injury mechanism included 10 cases of
      traffic accident, 6 cases of sports injury, and 3 cases of falls. The mean
      interval from injury to surgery was 34.9 d (ranged, 3 to 72 d). The affacted arm
      was suspended and fixed within 3 weeks after operation. The swing exercise of
      shoulder joint was performed from the 2nd day after operation. The strap was
      removed 3 weeks after operation, and painless active exercise was performed 6
      weeks after operation. The patients were followed up in the outpatient department
      6, 12 and 24 weeks after operation, and then every 6 months. AP and lateral X-ray
      films were taken at each follow-up time. At the latest follow-up, protractor was
      used to measure activity of patients; and VAS pain score, California University
      of Losangeles(UCLA) standard, American Shoulder and Elbow Surgeons (ASES) score
      were used to evaluate therapeutic effects. RESULTS: All the patients were
      followed up, with a mean duration of 35.2 months (ranged, 24 to 48 months). All
      the incisions were healed on the first stage without secondary acromion
      impingement and other complications. All the patients had bony union within 12
      weeks. The movements of shoulder joints including flexion, abduction, external
      rotation, internal rotation were increased obviously(P<0.05). The UCLA score was
      increased from preoperative 15.2+/-5.3 to 35.6+/-6.1 at the latest follow-up. The
      ASES score was increased from preoperative 31.2+/-5.4 to 91.2+/-6.8 at the latest
      follow-up (P<0.05). CONCLUSIONS: It has satisfactory curative effects for the
      avulsed fracture of humerus greater tuberosity using the double-row suture anchor
      fixation technique, especially the cases of small or comminuted fractures. It has
      several advantages such as firm fixation, simple and secure operation as well as
      quick postoperative recovery. Finally, patient should take exercises actively
      after operations.

PMID- 29455498
TI  - [Radiologic observation of the blood supply changes around the knee with
      osteoarthritis].
AB  - OBJECTIVE: To compare blood supply changes around the knee joint between normal
      and osteoarthritis knee. METHODS: From June 2014 to June 2015, 30 patients with
      knee osteoarthritis and 30 healthy adults were recruited. In osteoarthritis
      group, there were 9 males and 21 females, with a mean age of (65.967+/-7.132)
      years old(ranged, 53 to 82 years old), and the mean arterial pressure
      was(93.462+/-7.633) mmHg. In control group, there were 9 males and 21 females,
      with a mean age of (62.867+/-6.356) years old(ranged, 50 to 75 years old), and
      the mean arterial pressure was (92.122+/-9.675) mmHg. Inspection methods included
      color ultrasonic and computed tomography angiography of lower limbs. The patients
      were observed with: (1)collateral circulation; (2)artery circuity; (3)artery
      malformation; (4)artery stenosis; (5)arterial wall plaque formation. Stenosis was
      divided into 5 levels: level 1 as no narrow, level 2 as mild stenosis (1% to
      49%), level 3 as moderate stenosis (50% to 70%), level 4 as severe stenosis (70%
      to 99%), level 5 as total obstruction. Diameter and blood flow dynamics of
      popliteal artery, pretibial artery, and posterior tibia artery in two groups were
      measured and compared. RESULTS: The study was accomplished with complete data
      collection, none of the patients was eliminated, and there were no loss of follow
      up. There were 3 cases in OA group and 4 cases in control group with the
      formation of collateral circulation, and the difference had no statistically
      significance. There was none in OA group and 2 in control group with the
      formation of artery circuity, and the difference had no statistically
      significance. There were no cases in both groups with artery malformation. In OA
      group, there was mild in 14 cases, moderate in 7 cases, severe in 9 cases. In
      control group, there was no arterial stenosis in 9 cases, mild in 10 cases,
      moderate in 6 cases, severe in 4 cases, total obstruction in 1 case. The
      difference between two groups was statistically significant; artery stenosis in
      OA group was more severe than that of the control group. Artery plaque formed in
      30 cases in OA group and in 20 cases in control group. The difference between two
      groups was statistically significant; the rate of artery plaque formation in OA
      group was obviously higher than that of control group. In OA group, plaque
      calcification rate was 100% while 63% in control group. Difference of pretibial
      artery diameter was statistically significant, pretibial artery diameter is
      larger in OA group. Difference of popliteal artery flow velocity was
      statistically significant; velocity was faster in OA group. Difference of the
      posterior tibial artery flow velocity was statistically significant; velocity was
      faster in OA group. The differences of the three arteries had no statistical
      significances in related to arterial flow. CONCLUSIONS: Local artery system
      changes with the onset of knee joint osteoarthritis. Main pathological changesof
      local blood vessels were stenosis and plaque formation, but the amount of local
      artery blood flow was roughly the same as the control group. Possible mechanism
      is that the local artery stenosis speed up the artery blood flow velocity,
      resulting local perfusion. The local tissue ischemia and hypoxia caused a series
      of pathological changes. It is better to improve local vascular lesions than to
      accelerate the blood flow velocity in clinical treatment. Further more,
      interventional therapy for vascular pathology will be a new trend of
      osteoarthritis treatment.

PMID- 29455499
TI  - [Lateral closing wedge osteotomy and modified cross pinning with external tension
      band fixation in the treatment of cubitus varus deformity in childrenLateral
      closing wedge osteotomy and modified cross pinning with external tension band
      fixation in the treatment of cubitus varus deformity in children].
AB  - OBJECTIVE: To explore the therapeutic effects of distal humeral lateral closing
      wedge osteotomy followed by modified pinning combined with external tension band
      fixation in the treatment of cubitus varus deformity in children. METHODS: Total
      26 adult patients with cubitus varus deformity were treated by operation from
      March 2011 to June 2015, 15 patients were boys and the other 11 patients were
      girls, ranging in age from 4 to 13 years, with an average of 7.8 years. The
      cubitus varus angel ranged from 11 degrees to 24 degrees, with a mean(17.50+/
      6.73) degrees, 3 patients complicated more than 10 degrees constriction of
      flexion. Lateral closing wedge osteotomy retaining the medial 3 to 4 mm intact
      cortex by lateral elbow approach was applied in these 26 patients. The wedge
      defect were closed and fixed by crossing pinning. The lateral column compression
      was achieved with external tension band(the crossing pins were bended laterally
      and the pin ends were hooked mutually). The pre-operative, post-oparetive and
      contralateral carrying angles were compared and Laupattarakasem criteria was used
      to evaluate the results at follow-up. RESULTS: All the patients got bony union 2
      months after operation and there was no infection or nerve palsy. The average
      follow-up period was 18.8 months (ranged, 13 to 29 months). The carrying angle
      was restored to(11.50+/-3.17) degrees(ranged, 8 to 14 degrees). According to the
      Laupattarakasem evaluation criteria, 14 patients got an excellent result, 13 good
      and 1 fair. CONCLUSIONS: Normal carrying angle and elbow flexion could be
      restored by lateral closing wedge osteotomy, and stable fixation could be
      achieved with crossing pinning and external tension band, which is available for
      early mobilization.

PMID- 29455500
TI  - [Comparison and analysis of clinical effects of total arthroscopic repair and
      arthroscopic-assisted small incision repair for the treatment of rotator cuff
      injury].
AB  - OBJECTIVE: To investigate the clinical effects of arthroscopic repair and
      arthroscopic-assisted small incision repair for the treatment of rotator cuff
      injury. METHODS: The clinical data of 86 patients with rotator cuff injury from
      January 2012 to January 2015 were analyzed retrospectively. All the patients were
      divided into two groups: arthroscopic assisted small incision repair group(group
      A) and arthroscopic repair group(group B). There were 46 patients in group A,
      including 25 males and 21 females, with an average age of (52.8+/-7.8) years old.
      And there were 40 patients in group B, including 23 males and 17 females, with an
      average age of (53.2+/-9.5) years old. Several indexes such as shoulder joint
      activity, muscle strength and ASES, UCLA and VAS scores were examined before and
      after operation to compare therapeutic effects between these two groups. RESULTS:
      All the patients were followed up, and the mean time was 20.8 months (ranged, 18
      to 35 months). The results of patients in group A as follows: range of abduction
      motion of shoulder joint was (131.4+/-18.8) degrees , external rotation was
      (64.9+/-8.8) degrees , and internal rotation was(63.7+/-7.3) degrees . Results of
      patients in group B as follows: range of abduction motion of shoulder joint
      was(132.3+/-16.9), external rotation was(65.1+/-9.4) degrees , and internal
      rotation was(64.4+/-8.1) degrees . All the patients had better shoulder mobility
      than those before operation, but there were no significant differences between
      two groups after operation. Postoperative scores of patients in group A: ASES was
      88.4+/-8.9, UCLA score was 29.6+/-3.6, VAS was 1.4+/-0.3; and in group B, the
      above scores were 89.5+/-9.6, 30.8+/-4.1 and 1.3+/-0.4 respectively. All the
      patients had better scores than those before operation, but there were no
      significant differences between two groups after operation. CONCLUSIONS:
      Arthroscopic repair and arthroscopic-assisted small incision for repair of
      rotator cuff injury has clinical curative effects to some extent, and these two
      methods could improve the safety and reliability of surgical treatment.

PMID- 29455501
TI  - [Case-control study on the effect of core strength training on the function of
      anterior cruciate ligament reconstruction].
AB  - OBJECTIVE: To observe the effect of core strength training on knee joint function
      and postural stability after anterior cruciate ligament reconstruction (ACLR).
      METHODS: A total of 80 ACLR patients were randomly allocated into conventional
      rehabilitation training group and core strength training group from May 2013 to
      May 2015 with 40 patients in each group. The patients in conventional
      rehabilitation training group underwent conventional ACLR rehabilitation
      training, in which 28 males and 12 females. The mean age was(30.5+/-5.2) years
      old(ranged, 22 to 42 years old). The mean BMI was(23.8+/-2.4) kg/m2(ranged, 18.2
      to 25.9 kg/m2). Thirty patients had injuries on the dominant side and 10 patients
      had injuries on the non-dominant side. The core strength training group received
      conventional ACLR rehabilitation training and core strength training, in which 31
      males and 9 females. The mean age was(31.1+/-4.8) years old(ranged, 21 to 45
      years old). The mean BMI was(24.1+/-2.7) kg/m2(ranged, 18.5 to 26.1 kg/m2) .
      Twenty-seven patients had injuries on the dominant side and 13 patients had
      injuries on the non-dominant side. The Lysholm score, tibial anterior transition
      measured by KT-1000 before and after treatment, and the Star Excursion Balance
      Test results after treatment were compared between the two groups. RESULTS: Six
      months after rehabilitation training, the tibial anterior transition of the
      conventional rehabilitation training group and the core strength training group
      were(3.4+/-1.0) mm and(3.3+/-1.2) mm respectively, which were less than(12.1+/
      1.8) mm and(12.5+/-2.0) mm before treatment. But there was no significant
      difference in anterior tibial translation between two groups(P>0.05). The Lysholm
      score of the conventional rehabilitation training group and the core strength
      training group were 91.8+/-4.3 and 92.1+/-3.9 individually, which were higher
      than 69.2+/-5.8 and 70.2+/-5.1 before treatment. But there was no significant
      difference in Lysholm score between two groups(P>0.05). Six months after
      rehabilitation training, the results of Star Excursion Balance Test showed the
      reach distance with the support in the injured side and healthy side in the core
      strength training group were greater than that of the conventional rehabilitation
      training group in the eight directions(P<0.05). CONCLUSIONS: The core strength
      training could improve the dynamic balance of ACLR patients.

PMID- 29455502
TI  - [Case-control study on the effect of meniscus shaping on knee function after
      anterior cruciate ligament reconstruction].
AB  - OBJECTIVE: To observe the effect of the meniscus shaping on the knee function and
      stability after anterior cruciate ligament reconstruction(ACLR). METHODS: A total
      of 64 ACLR patients were included from January 2013 to January 2015. The control
      group was the ACLR patients with intact meniscus, in which 24 males and 6
      females. The mean age was(32.8+/-5.5) years old(ranged, 22 to 43 years old). The
      injury side was left on 17 cases and right on 13 cases. The mean follow-up time
      was(15.2+/-2.8) months(ranged, 12 to 19 months). The shaping group was the ACLR
      patients with meniscus shaping, in which 27 males and 7 females. The mean age was
      (33.1+/-4.2) years old (ranged, 23 to 42 years old). The injury side was on the
      left in 22 case and right in 12 cases. The mean follow-up time was (16.0+/-3.1)
      months (ranged, 12 to 20 months). The preoperative anterior tibia shift and knee
      joint function, as well as anterior tibia shift, knee joint function and active
      proprioception at last follow-up time were observed. The anterior tibia shift was
      measured by KT-1000. The knee joint function was assessed by Lysholm score and
      KOOS score. The errors of active proprioception were measured at 30 degrees , 45
      degrees  and 60 degrees  knee flexion. RESULTS: Postoperative anterior tibia
      shift of the affected side was (1.4+/-0.2) mm, which was lower than (2.2+/-0.4)
      mm in shaping group(P<0.05). The postoperative total Lysholm scores of the
      control group and the shaping group were 93.7+/-2.7 and 92.3+/-3.0 respectively,
      which were higher than 52.8+/-3.9 and 51.6+/-5.1 preoperatively(P<0.05), but
      there were no significant differences between two groups(P>0.05). In the KOOS
      score, the postoperative symptoms, pain, daily life, exercise capacity and life
      quality in control group were 90.7+/-5.5, 93.2+/-4.3, 96.8+/-2.2, 90.9+/-5.3,
      91.8+/-4.5 respectively, which were higher than 72.7+/-6.0, 70.6+/-7.3, 72.5+/
      7.4, 52.8+/-5.4, 36.2+/-6.5 preoperatively(P<0.05); the postoperative symptoms,
      pain, daily life, exercise capacity and life quality in the shaping group were
      88.9+/-5.8, 92.6+/-3.5, 96.5+/-2.1, 89.3+/-7.2, 90.6+/-4.1 respectively, which
      were higher than 71.9+/-5.1, 71.2+/-7.1, 71.3+/-6.2, 53.1+/-6.1, 35.6+/-4.7
      preoperatively(P<0.05). No significant differences were observed in each
      postoperative item of KOOS between the two groups(P>0.05). No significant
      differences were observed in the postoperative active proprioception error of
      contralateral side between the control group(12.2+/-3.4) degrees and shaping
      group(12.8+/-3.2) degrees (P>0.05). The error of active proprioception in the
      affacted side of the control group was(13.5+/-3.7) degrees , which was lower than
      that in the shaping group(17.1+/-4.2) degrees (P<0.05). In control group, there
      was no significant difference in the active proprioception error between two
      sides(P>0.05). While in shaping group, the error of active proprioception in the
      affacted side was significantly greater than that in the contralateral
      side(P<0.05). CONCLUSIONS: In short and medium term, meniscus shaping has no
      effect on knee joint function in patients with ACLR, but it impairs the knee
      proprioception and stability.

PMID- 29455503
TI  - [Diagnostic value of Blumensaat angle for anterior cruciate ligament injury].
AB  - OBJECTIVE: The receiver operator characteristic(ROC) curve was used to determine
      the best Blumensaat angle for the diagnosis of anterior cruciate ligament injury,
      so as to objectively evaluate the diagnostic value of Blumensaat angle for
      anterior cruciate ligament injury. METHODS: Total 167 patients who had knee
      arthroscopic treatment in a hospital from January 2015 to January 2016 were
      retrospectively studied, and the patients' age, gender, left and right limb
      condition were recorded. The patients were divided into two groups according to
      Blumensaat angle measured on the MRI: group A(Blumensaat angle<=0 degrees ), and
      group B(Blumensaat angle >0 degrees ). The ROC curve was drawn from the
      statistical data of the group B to get the best critical value of the anterior
      cruciate ligament injury when the Blumensaat angle was more than 0 degrees .
      According to the best critical value obtained by ROC curve, the coincidence rate
      of the total sample was obtained. RESULTS: There were no significant differences
      in patients' age, gender, and affected limbs. There were 51 patients in group A,
      in which 49 patients were diagnosed as anterior cruciate injury under
      arthroscopy(gold standard for diagnosis of anterior cruciate ligament injury),
      and 2 patients were diagnosed as no anterior cruciate injury under arthroscopy.
      When the Blumensaat angle was<0 degrees , the coincidence rate was 96.07%. In
      group B(116 cases), the area under the ROC curve was 0.910, the best cutoff
      corresponds to 15 degrees ; the sensitivity was 70.0%, and the specificity was
      95.8%. When the Blumensaat angle was >=15 degrees , the probability of anterior
      cruciate ligament injury was greater. When the Blumensaat angle was 0 degrees  to
      15 degrees , the anterior cruciate ligament was more likely to be not injured.
      The Blumensaat angle<=0 degrees or>=15 degrees  were used to diagnose the injury
      of anterior cruciate ligament. Compared with the results of arthroscopy, the
      coincidence rate of the total sample was 92.8%. CONCLUSIONS: Blumensaat angle is
      helpful to diagnose the ACL injuries. When the Blumensaat angle was <=0 degrees 
      or >=15 degrees , the probability of ACL injury is greater.

PMID- 29455505
TI  - [Femoral supracondylar osteotomy for the treatment of valgus knee osteoarthritis
      in young and middle-aged patients].
AB  - OBJECTIVE: To evaluate the clinical efficacy of open supracondylar osteotomy of
      the femoral condyle for the treatment of valgus knee osteoarthritis. METHODS:
      From April 2008 to June 2015, 21 patients with valgus knee osteoarthritis
      underwent an open wedge femoral supracondylar osteotomy using the distal femur
      dissection plates combined with autologous iliac bone graft for the bone defect.
      There were 8 males (8 knees) and 13 females (15 knees), ranging in age from 30 to
      54 years old, with a mean age of 41.2 years old. All the patients had valgus
      deformity and knee joint pain in the lateral compartment. The average
      tibiofemoral angle was (162.0+/-2.6) degrees  which was measured on the image of
      preoperative lower extremity weight-bearing X-ray. Clinical outcomes were
      comprehensively assessed according to the bone healing time, postoperative
      complications, progress of knee osteoarthritis after operation, the Hospital for
      Special Surgery rating system (HSS), and tibiofemoral angle before and after
      operation. RESULTS: All 21 patients were followed up, the valgus deformity of
      knee joint was corrected in all patients after operation. No obvious delayed
      union or nonunion were found, and no serious complications were found. The HSS
      knee score was improved from the preoperative 57.3+/-3.1 to the final follow-up
      time 88.6+/-2.7. Tibiofemoral angle was improved to the postoperative(176.0+/
      1.4) degrees . CONCLUSIONS: Open wedge femoral supracondylar osteotomy has a
      clear surgical approach, and it is easy to control the bone mass of osteotomy and
      can effectively correct the valgus deformity and improve the function of knee
      joint using this method. It is an effective method for the treatment of valgus
      knee osteoarthritis in young and middle-aged patients.

PMID- 29455504
TI  - [Clinical effects of rehabilitation exercise in the treatment of knee
      osteoarthritis based on the theory of "treating muscle for bone"].
AB  - OBJECTIVE: To study the efficacy and safety of voluntary rehabilitation exercise
      in the treatment of knee osteoarthritis, based on the traditional Chinese
      medicine theory of "treating muscle for bone". METHODS: Ninety participants with
      early knee osteoarthritis were randomly divided into experimental group (n=45)
      and control group (n=45). Patients in experimental group were treated with
      voluntary rehabilitation exercise combined with isometric extension of quadriceps
      femoris. Patients in control group were treated with apparatus training combined
      with isometric extension of quadriceps femoris. The treatment course lasted for
      two weeks. Visual analogue scale (VAS), Lysholm score and total therapeutic
      effect were evaluated before and after treatments. RESULTS: After two weeks of
      treatment, cure-remarkable-effective rate in experimental group (86.67%) was
      higher than that in control group (71.11%). The VAS scores and Lysholm scores
      were significantly improved in both two groups (P<0.05). The results were
      significantly better in experimental group those in control group (P<0.05). There
      were no serious adverse events. CONCLUSIONS: Voluntary rehabilitation exercise
      combined with isometric extension of quadriceps femoris was effective and safe in
      the treatment of early knee osteoarthritis.

PMID- 29455506
TI  - [Application of greater trochanteric slide osteotomy in total hip arthroplasty
      for stiff hip].
AB  - OBJECTIVE: To study the effect of greater trochanteric slide osteotomy(GTSO) in
      total hip arthroplasty (THA) for the treatment of stiff hip, as well as the
      potential complications. METHODS: There were 12 cases enrolled in the study from
      April 2010 to December 2014, including 9 males and 3 females. The mean age was
      49.9 years old (ranged, 37 to 62 years old). The clinical result was evaluated
      according to the Harris evaluation system, and the radiological evaluations
      included the healing of the osteotomy, the stability of the prosthesis, and
      occurrence of heterotopic ossification (HA). RESULTS: The mean follow-up period
      was 17.3 months (ranged, 15 to 22 months). The mean postoperative Harris score
      was 88.00+/-6.11, which was significantly higher than the preoperative mean score
      which was 43.96+/-8.46(t=-18.34, P=0.00). All the osteotomy site abtained good
      healing without prosthesis loosening or HA. There was 1 patient with infection
      and 1 patient with pain in greater trochanter. CONCLUSIONS: GTSO is an effective
      exposure technique in THA for stiff hip, and no marked complication associated
      with the osteotomy is found in the study.

PMID- 29455507
TI  - [Effect and mechanism of total flavone of epimedium on primary callus formation
      in ovariectomized rats with fractures].
AB  - OBJECTIVE: To explore the effects and related mechanisms of total flavone of
      epimedium treatment(TFE)on primary callus for mation in ovariectomized rats.
      METHODS: Forty male SD rats weighted from 209 to 246 g and aged 6 to 8 weeks were
      selected. Six weeks after ovariectomy a femur fracture model with middiaphyseal
      segment fracture was established, estimated and randomly divided into TFE group
      (150 mg.kg-1.d-1) and control group(received saline). HE staining was used to
      evaluate the morphologic difference of primary callus during the bone callus
      healing between these two groups. The relative expression of Runt-related
      transcription factor 2(Runx2) mRNA in the callus was identified by real-time
      polymerase chain reaction. Immunohistochemical technique was used to observe the
      Casein kinase 2-interacting protein 1(CKIP-1) protein level in the callus of the
      two groups. Maximum fracture load was tested by three point bend test. RESULTS:
      The BMD, primary callus volume, trabecular member(Tb.N) and trabecular
      thickness(Tb.Th) were higher in TFE group than that in control group(P<0.001).
      The Tb.N and Tb.Th of primary callus were higher in TFE group than control group
      (P=0.001). The volume and bone volume/tissue volume of primary callus were in TFE
      group than control group(P<0.01). The trabecular separation(Tb.Sp) of primary
      callus were in control group higher than TFE group(P<0.01). The HE staining of
      the 6 week slices showed that the degree of cartilage ossification in callus of
      the TFE group was significantly higher than that in control group under high
      magnification. Real-time PCR revealed that the comparative expression of Runx2
      mRNA in control group was higher than that in TFE group(P<0.001); the positive
      number of CKIP-1 was less in TFE group than that in control group (P<0.001). TFE
      could increase the maximum load of the primary callus (P<0.001). CONCLUSIONS: TFE
      can promote the cartiage ossification of callus in ovariectomized rats, enhancing
      the bone strength and bone quality in the process of fracture healing via the
      CKIP-1/Runx2 pathway.

PMID- 29455508
TI  - [Clinical effects of arthroscopic microfracture on osteochondral lesions of the
      talus].
AB  - OBJECTIVE: To evaluate the clinical effects of arthroscopic microfracture on
      osteochondral lesions of the talus. METHODS: Total 42 patients with osteochondral
      lesions of the talus, who were collected in our department from January 2011 to
      December 2013. The patients were 35.9 years old on average, including 28 males
      and 14 females. There were 34 patients who had injury histories. The debridement
      and microfracture were performed under arthroscopy. The function of ankle was
      assessed according to AOFAS Ankle Hindfoot Scale. MRI of ankle was checked 2
      years postoperatively. RESULTS: There were 23 cases in stage 3, 9 cases in stage
      4 and 10 cases in stage 5 in MRI. There were 25 cases on the 4th district, 11
      cases on the 6th district, 4 cases on the 1st district, 2 cases on the 3rd
      district according to 9 districts location and 8 cases of subchondral cyst found
      on the 4th district. AOFAS Ankle Hindfoot Scale of all patients on the 1st year
      postoperatively was 73.3+/-3.9 which was significantly better than 50.4+/-7.8
      preoperatively, and 81.1+/-4.8 on the 2nd year postoperatively was also
      significantly better than that on the 1st year postoperatively. CONCLUSIONS:
      Arthroscopic microfracture for the osteochondral lesions of the talus could have
      a good clinical effect.

PMID- 29455509
TI  - [Treatment of Sanders II calcaneus fractures via minimally invasive sinus tarsi
      approach].
AB  - OBJECTIVE: To study the feasibility and clinical efficacy of a minimally invasive
      sinus tarsi approach in the treatment of Sanders II calcaneus fractures. METHODS:
      From August of 2015 to July of 2016, 13 patients(totally 13 feet) with Sanders II
      intra-articular calcaneus fractures were treated via the minimally invasive sinus
      tarsi approach. The Bohler angle, Gissane angle and the length, width and height
      of calcaneus were compared between pre-operation and post-operation. The AOFAS
      ankle and foot scoring system of the orthopaedic ankle foot Association was used
      to evaluate the efficacy. RESULTS: All the patients were followed up, and the
      duration ranged from 6 to 15 months, with an average of 9.5 months. No incision
      complications occurred. The Bohler angle was increased from preoperative (18.82+/
      5.11) degrees  to postoperative(26.63+/-4.45) degrees (t=-4.16, P=0.000). The
      Gissane angle was increased from preoperative(111.07+/-15.36) degrees  to
      postoperative (124.56+/-8.71) degrees  (t=-2.75, P=0.011). The length, width,
      height of calcaneus were absolutely improved from preoperative(69.82+/-5.95) mm,
      (42.07+/-3.68) mm, (41.20+/-3.90) mm to preoperatively(72.61+/-5.46) mm, (39.10+/
      4.02) mm, (44.03+/-3.33) mm. According to the AOFAS, 8 patients got an excellent
      result, 4 good and 1 poor, and the postoperative mean score was 88.2+/-5.9.
      CONCLUSIONS: The limited open sinus tarsi approach could be used successfully to
      treat displaced Sanders II fractures with less injury and effectively restored
      the surface of subtalar joint, however the method is not fit for the patients
      with comminuted fracture in lateral wall and great change in the length, width,
      height, varus and valgus of calcaneus.

PMID- 29455510
TI  - [Application of high fibular osteotomy in the treatment of knee osteoarthritis].
AB  - OBJECTIVE: To evaluate the short-and mid-term curative effect of high fibular
      osteotomy on knee osteoarthritis. METHODS: From October 2014 to July 2016, 76
      patients with knee osteoarthritis were treated with high fibular osteotomy. There
      were 22 males and 54 females, ranging in age from 47 to 82 years old, with an
      average of 61.62 years old. Internal tenderness of the knee joint was examined
      preoperatively. Preoperative examination showed medial knee pain and medial
      positive McMurray sign. Preoperative AP and lateral X-ray films of the weight
      bearing side of the knee showed the narrowing of the medial space. The knee
      medial space, femoral and tibial angle, VAS pain score and the American Knee
      Society(AKS) score were evaluated after operation. RESULTS: Compared with the
      preoperative one, the postoperative knee medial gap was widened obviously. The
      femur and tibia angle after operation was bigger than that before surgery. The
      VAS was improved from preoperative 5.70+/-1.56, to 3.70+/-1.03 at the 1st week
      after operation, 3.20+/-0.95 at the 1st month after operation, 2.35+/-0.99 at the
      3rd month after operation, and 2.10+/-0.97 at the 1st year after operation.
      According to the AKS score, the preoperative pain score of knee joint was 14.45+/
      1.76, the activity score of knee joint was 12.60+/-1.98, and the stability score
      was 12.15+/-1.72; after operation, the above scores were improved to 42.60+/
      2.28, 21.80+/-2.14, and 20.85+/-2.16 respectively. CONCLUSIONS: The high fibular
      osteotomy with less complications is simple. It can effectively alleviate the
      pain of the knee joint and improve the function of knee joint, and the clinical
      effect is satisfactory.

PMID- 29455511
TI  - [Treatment of gouty arthritis of the first metatarsophalangeal joint by Masquelet
      technique].
AB  - OBJECTIVE: To study clinical curative effects of a Masquelet technology in the
      treatment of gouty arthritis in the first metatarsophalangeal joint. METHODS:
      From February 2012 to May 2016, 7 patients with the gouth arthritis of the first
      metatarsophalangeal joint were treated by the Masqueket technology. There were 5
      males and 2 females, ranging in age from 42 to 58 years old, with an average age
      of 50 years old. During the regular follow up, the bone healing was assessed by
      the radiographic imaging, and the orthopaedic foot and ankle Association (AOFAS)
      ankle function scoring system was used for comprehensive evaluation. RESULTS: All
      the patients were followed up, and the duration ranged from 6 to 8 months, with a
      mean of 7 months. All the wounds obtained first intention healing, and there were
      no complications such as wound infection, flap necrosis and other soft tissue
      complications. The time to bone healing was 3 to 4 months, with an average of 3.6
      months. The AOFAS score was increased from preoperative 42.5+/-4.6 to
      postoperative 85.0+/-10.5. CONCLUSIONS: The application of Masquelet technique in
      the treatment of first metatarsophalangeal joint gouty arthritis achieves obvious
      symptom relief, has less complications, and can effectively improve the quality
      of life of patients, which is a new and effective treatment.

PMID- 29455512
TI  - [Rapture of the patellar ligament and the contralateral femoral quadriceps tendon
      in uremia patients].

PMID- 29455513
TI  - [Cervical spinal epidural and subdural hematoma after acupuncture: a case
      report].

PMID- 29455514
TI  - [Current knowledge in the treatment of anterolateral ligament injury of knees].
AB  - Although the function of the anterolateral stabilizing structures of the knee in
      the anterior cruciate ligament (ACL) injuries has been recognized since many
      years, most of orthopedic surgeons do not take the anterolateral structure into
      consideration when performing an ACL reconstruction. Anatomic ACL reconstruction
      will improve knee stability, but a small subset of patients may experience some
      residual anteroposterior and rotational instability. For this reason, some
      researchers have paid attention to the anterolateral aspects of the knee,
      especially the anterolateral ligament. We don't know the best time to perform ACL
      and ALL reconstruction. And we lack the evidence to prove which technique is the
      best one. So we look forward to more random controlled trial.

PMID- 29455515
TI  - [Research on promotory effect of traditional Chinese medicine on fracture healing
      in cell and molecular level].
AB  - Traditional Chinese medicine is widely used in the treatment of fractures,
      osteoporosis, other bone related diseases for thousands of years. There are many
      animal experiments and clinical trials demonstrating that the traditional Chinese
      medicine such as epimedium, Drynaria and other traditional Chinese medicine can
      stimulate bone regeneration and inhibit bone resorption, accelerating the
      fracture healing. In recent years many cell experiments have shown that these
      herbal ingredients up-regulated the expression of intracellular osteogenic
      transcription factors and osteogenic related genes, and then induced osteoblastic
      differentiation and stimulated the proliferation of osteoblasts, bone nodule
      formation and matrix mineralization. Meanwhile these herbal ingredients up
      regulated the expression of intracellular osteoclastic transcription factors and
      osteoclast related genes, inhibited osteoclast differentiation and bone
      resorption of osteoclasts. In addition, intracellular signaling pathways
      regulated these herbal ingredients by might be involved in the above effects. We
      can have a conclusion that the genes expression regulated by transcription
      factors in pre-osteoblast and pre-osteoclast and these signaling pathways are the
      major molecular mechanisms and research hotspots of traditional Chinese medicine
      in promoting fracture healing. Based on these molecular mechanisms to review,
      this review provides not only the foundation for the study of traditional Chinese
      medicine in promoting fracture healing, but also the basis for clinical treatment
      of fracture.

PMID- 29455516
TI  - Core-Shell Microneedle Gel for Self-Regulated Insulin Delivery.
AB  - A bioinspired glucose-responsive insulin delivery system for self-regulation of
      blood glucose levels is desirable for improving health and quality of life
      outcomes for patients with type 1 and advanced type 2 diabetes. Here we describe
      a painless core-shell microneedle array patch consisting of degradable cross
      linked gel for smart insulin delivery with rapid responsiveness and excellent
      biocompatibility. This gel-based device can partially dissociate and subsequently
      release insulin when triggered by hydrogen peroxide (H2O2) generated during the
      oxidation of glucose by a glucose-specific enzyme covalently attached inside the
      gel. Importantly, the H2O2-responsive microneedles are coated with a thin-layer
      embedding H2O2-scavenging enzyme, thus mimicking the complementary function of
      enzymes in peroxisomes to protect normal tissues from injury caused by oxidative
      stress. Utilizing a chemically induced type 1 diabetic mouse model, we
      demonstrated that this smart insulin patch with a bioresponsive core and
      protective shell could effectively regulate the blood glucose levels within a
      normal range with improved biocompatibility.

PMID- 29455517
TI  - Highly Sensitive Bulk Silicon Chemical Sensors with Sub-5 nm Thin Charge
      Inversion Layers.
AB  - There is an increasing demand for mass-producible, low-power gas sensors in a
      wide variety of industrial and consumer applications. Here, we report chemical
      sensitive field-effect-transistors (CS-FETs) based on bulk silicon wafers,
      wherein an electrostatically confined sub-5 nm thin charge inversion layer is
      modulated by chemical exposure to achieve a high-sensitivity gas-sensing
      platform. Using hydrogen sensing as a "litmus" test, we demonstrate large sensor
      responses (>1000%) to 0.5% H2 gas, with fast response (<60 s) and recovery times
      (<120 s) at room temperature and low power (<50 MUW). On the basis of these
      performance metrics as well as standardized benchmarking, we show that bulk
      silicon CS-FETs offer similar or better sensing performance compared to emerging
      nanostructures semiconductors while providing a highly scalable and
      manufacturable platform.

PMID- 29455518
TI  - Surface Adatom Mediated Structural Transformation in Bromoarene Monolayers:
      Precursor Phases in Surface Ullmann Reaction.
AB  - Structural transformations of supramolecular systems triggered by external
      stimuli maintain great potential for application in the fabrication of molecular
      storage devices. Using combined ultrahigh vacuum scanning tunneling microscopy, X
      ray photoemission spectroscopy, and density functional theory calculations, we
      observed the surface adatom mediated structural transformation from 4,4''-dibromo
      m-terphenyl (DMTP)-based halogen-bonded networks to DMTP-Cu(Ag) coordination
      networks on Cu(111) and Ag(111) at low temperatures. The halogen-bonded networks,
      which were formed on Cu(111) at 97 K and on Ag(111) at 93 K, consist of intact
      DMTP molecules stabilized by triple Br...Br bonds. The DMTP-Cu(Ag) coordination
      networks form on Cu(111) at 113 K and on Ag(111) at 103 K. They contain
      alternatingly arranged intact DMTP molecules and Cu(Ag) adatoms stabilized by
      weak C-Br...Cu(Ag) coordination bonds. Annealing the DMTP-Ag structure to 333 K
      leads to the initiation of C-Br bond scission. This observation suggests that the
      DMTP-Ag coordination network represents the intermediate phase ready for
      dehalogenation, which is the first step of the surface Ullmann reaction.

PMID- 29455519
TI  - A Self-Targeting, Dual ROS/pH-Responsive Apoferritin Nanocage for
      Spatiotemporally Controlled Drug Delivery to Breast Cancer.
AB  - In this study, an intelligent pH and ROS dual-responsive drug delivery system
      based on an apoferritin (AFt) nanocage was prepared. This therapeutic system can
      specifically self-target 4T1 breast cancer cells by exploiting L-apoferritin
      receptor SCARA 5, avoiding the nonspecific binding or aggregation of
      nanoparticles due to the chemical functionalization for targeting. The
      characteristics of AFt were utilized for the simultaneous delivery of anticancer
      drug doxorubicin (DOX) and photosensitizer rose bengal (RB). RB exhibited
      efficient reactive oxygen species (ROS) generation, which can be applied to
      photodynamic therapy. Meanwhile, the AFt nanocage was prone to undergoing peptide
      backbone cleavage when oxidized by ROS. Therefore, by combining the intrinsic pH
      responsive property of AFt, the dual ROS/pH-responsive system was developed. The
      time and location of drug release can be controlled by the combination of
      internal and external stimulus, which avoids the incomplete drug release under
      single stimulus response. The drug release rate increased significantly (from
      26.1% to 92.0%) under low-pH condition (pH 5.0) and laser irradiation. More DOX
      from AFt entered the nucleus and killed the tumor cells, and the cell inhibition
      rate was up to ~83% (DOX concentration: 5 MUg/mL) after 48 h incubation. In
      addition, the biodistribution and the in vivo antitumor efficacy (within 14 d
      treatment) of the nanosystem were investigated in 4T1 breast cancer BALB/c mice.
      The results indicated that the system is a promising therapeutic agent involving
      ROS/pH dual response, self-targeting, and chemo-photodynamic therapy.

PMID- 29455520
TI  - Safety Assessments and Multiplicity Adjustment: Comments on a Recent Paper.

PMID- 29455521
TI  - Self-Assembled Binuclear Cu(II)-Histidine Complex for Absolute Configuration and
      Enantiomeric Excess Determination of Naproxen by Tandem Mass Spectrometry.
AB  - Naproxen is one of the most consumed nonsteroidal anti-inflammatory drugs and
      marketed as S-naproxen since R-naproxen is hepatotoxic. In this study, chiral
      recognition of naproxen has been investigated by tandem mass spectrometry
      (MS/MS). Among all diastereomeric complexes formed between naproxen and the
      examined chiral selectors, including cyclodextrins (alpha/beta/gamma-CD),
      modified phenylalanines ( N-acetyl-phenylalanine, N-t-butoxycarbonyl
      phenylalanine, N-9-fluorenylmethyloxycarbonyl-phenylalanine), amino acids (Trp,
      Phe, Tyr, His), glucose, tartaric acid, and vancomycin, a novel binuclear metal
      bound diastereomeric complexes [(M(II))2( S/ R-naproxen)(l-His)2-3H]+ (M = Cu,
      Ni, or Co with Cu being the best) could allow effective identification of the
      absolute configuration of naproxen and determination of its enantiomeric excess (
      ee) through MS/MS analysis. The key candidate structure of [(Cu(II))2( S/ R
      naproxen)(l-His)2-3H]+ has been revealed by means of collision-induced
      dissociation, ion mobility mass spectrometry and density functional theory
      calculations, indicating an interesting and unusual self-assembled compact
      geometry with the two Cu(II) ions bridged closely together (Cu-Cu distance is
      3.04 A) by the carboxylate groups of the two histidines. It was shown that the
      difference in dissociation efficiency between the two diastereomers was
      attributed to the interaction between the NH2 bond of the amino group of one
      histidine and the naphthyl ring of naproxen. The present report is the first to
      observe and characterize the complex of (Cu(II))2(His)2 with aromatic acid, which
      could contribute to the chiral recognition of other chiral aromatic acids, design
      of catalysts based on binuclear copper bound complex, as well as the better
      understanding of metal ion complexation by His or His-containing ligands.

PMID- 29455522
TI  - All-MXene-Based Integrated Electrode Constructed by Ti3C2 Nanoribbon Framework
      Host and Nanosheet Interlayer for High-Energy-Density Li-S Batteries.
AB  - High-energy-density lithium-sulfur (Li-S) batteries hold promise for next
      generation portable electronic devices, but are facing great challenges in
      rational construction of high-performance flexible electrodes and innovative cell
      configurations for actual applications. Here we demonstrated an all-MXene-based
      flexible and integrated sulfur cathode, enabled by three-dimensional alkalized
      Ti3C2 MXene nanoribbon (a-Ti3C2 MNR) frameworks as a S/polysulfides host (a-Ti3C2
      S) and two-dimensional delaminated Ti3C2 MXene (d-Ti3C2) nanosheets as interlayer
      on a polypropylene (PP) separator, for high-energy and long-cycle Li-S batteries.
      Notably, an a-Ti3C2 MNR framework with open interconnected macropores and an
      exposed surface area guarantees high S loading and fast ionic diffusion for
      prompt lithiation/delithiation kinetics, and the 2D d-Ti3C2 MXene interlayer
      remarkably prevents the shuttle effect of lithium polysulfides via both chemical
      absorption and physical blocking. As a result, the integrated a-Ti3C2-S/d
      Ti3C2/PP electrode was directly used for Li-S batteries, without the requirement
      of a metal current collector, and exhibited a high reversible capacity of 1062
      mAh g-1 at 0.2 C and enhanced capacity of 632 mAh g-1 after 50 cycles at 0.5 C,
      outperforming the a-Ti3C2-S/PP electrode (547 mAh g-1) and conventional a-Ti3C2-S
      on an Al current collector (a-Ti3C2-S/Al) (597 mAh g-1). Furthermore, the all
      MXene-based integrated cathode displayed outstanding rate capacity of 288 mAh g-1
      at 10 C and long-life cyclability. Therefore, this proposed strategy of
      constructing an all-MXene-based cathode can be readily extended to assemble a
      large number of MXene-derived materials, from a group of 60+ MAX phases, for
      applications such as various batteries and supercapacitors.

PMID- 29455524
TI  - Multiwall Carbon Nanotubes Induce More Pronounced Transcriptomic Responses in
      Pseudomonas aeruginosa PG201 than Graphene, Exfoliated Boron Nitride, or Carbon
      Black.
AB  - Carbonaceous and boron nitride (BN) nanomaterials have similar applications and
      hydrophobic properties suggesting common release pathways and exposure to
      bacteria. While high nanomaterial concentrations can be bactericidal or growth
      inhibitory, little is known regarding bacterial transcriptional responses to non
      growth-inhibitory nanomaterial concentrations. Here, using one strain of
      Pseudomonas aeruginosa-a clinically and environmentally important bacterial taxon
      we analyzed the comparative transcriptomic response to carbonaceous or BN
      nanomaterials. We show that, at non-growth-inhibitory, equal mass concentrations
      (10 mg/L), multiwall carbon nanotubes (MWCNTs) induced differential regulation of
      111 genes in P. aeruginosa, while graphene, BN, and carbon black caused
      differential regulation of 44, 26, and 25 genes, respectively. MWCNTs caused the
      upregulation of genes encoding general stress response (9 genes), sulfur
      metabolism (15), and transport of small molecules (7) and downregulation of genes
      encoding flagellar basal-body rod proteins and other virulence-related factors
      (6), nitrogen metabolism (7), and membrane proteins (12), including a two
      component regulatory system CzcS/R. Because two-component systems are associated
      with antibiotic resistance, the antibiotic susceptibility of P. aeruginosa was
      tested following MWCNT exposure. In MWCNT-treated cultures, the minimal
      inhibitory concentrations (MICs) of meropenem and imipenem decreased from 0.06 to
      0.03 MUg/mL and from 0.25 to 0.125 MUg/mL, respectively. Taken together, whole
      genome analysis indicated that, in the absence of growth inhibition,
      nanomaterials can alter bacterial physiology and metabolism. For MWCNTs, such
      alterations may include downregulation of antibiotic resistance pathways,
      suggesting that pre-exposure to MWCNTs could potentially render bacteria more
      susceptible to carbapenems which are often the last resort for the globally
      concerning, highly antibiotic resistant P. aeruginosa.

PMID- 29455523
TI  - Sonchus oleraceus Residue Improves Nutritive and Health-Promoting Value of Common
      Bean ( Phaseolus vulgaris L.): A Metabolic Study.
AB  - This study was conducted to evaluate the use of the phenolic-rich Sonchus
      oleraceus residue as an environmentally safe approach to induce the nutritive and
      health-promoting values of common bean ( Phaseolus vulgaris L. cv. Bronco). S.
      oleraceus shoot residue, at rates of 150 and 300 g m-2, has improved soil
      fertility via accumulation of soil macronutrients, organic matter, organic
      carbon, and total phenolics. The growth and yield of bean were significantly
      increased. Moreover, chemical composition of the treated seeds was significantly
      altered, whereas higher levels of total antioxidant capacity, proteins,
      carbohydrates, and most of the individual phenolic acids, flavonoids, vitamins,
      essential amino acids, and unsaturated fatty acids were recorded. Interestingly,
      a concentration dependent effect was also observed, for instance, a lower
      saturated-to-unsaturated fatty acid ratio was only observed in the case of the
      lower residue rate. These findings recommend the use of S. oleraceus in organic
      farming of bean to enhance the health benefits of the produced seeds.

PMID- 29455525
TI  - Graphene Oxide Decorated with Cerium(IV) Oxide in Determination of Ultratrace
      Metal Ions and Speciation of Selenium.
AB  - Graphene oxide decorated with cerium(IV) oxide (GO/CeO2) was synthesized and
      applied in adsorption of several metal ions such as As(III), As(V), Se(IV),
      Cu(II), and Pb(II) from aqueous samples. The important feature of GO/CeO2
      nanocomposite is also its selectivity toward selenite in the presence of
      selenate. The structure of GO/CeO2 has been proven by microscopic and
      spectroscopic techniques. The maximum adsorption capacities of GO/CeO2 calculated
      by Langmuir model toward arsenic, selenium, copper, and lead ions are between 6
      and 30 mg g-1. An interesting feature of this adsorbent is its excellent
      dispersibility in water. Thus, GO/CeO2 nanocomposite is ideal for fast and simple
      determination of heavy metal ions using dispersive microsolid phase extraction
      (DMSPE). Moreover, coupling DMSPE with energy-dispersive X-ray fluorescence
      spectrometry (EDXRF) is extremely beneficial because it allows direct analysis of
      adsorbent. Thus, the analyte elution step, as needed in many analytical
      techniques, was obviated. The influence of sample volume and the sorption time as
      well as the influence of foreign ions and humic acid on the recovery of
      determined elements are discussed in the paper. The results showed that developed
      methodology provided low limits of detection (0.07-0.17 MUg/L) and good precision
      (RSD < 4%). The GO/CeO2 nanocomposite was applied to analysis of real water
      samples and certified reference materials (CRM) groundwater (BCR-610) and pig
      kidney (ERM-BB186).

PMID- 29455526
TI  - Structure-Based Optimization Strategies for G Protein-Coupled Receptor (GPCR)
      Allosteric Modulators: A Case Study from Analyses of New Metabotropic Glutamate
      Receptor 5 (mGlu5) X-ray Structures.
AB  - Two interesting new X-ray structures of negative allosteric modulator (NAM)
      ligands for the mGlu5 receptor, M-MPEP (3) and fenobam (4), are reported. The new
      structures show how the binding of the ligands induces different receptor water
      channel conformations to previously published structures. The structure of
      fenobam, where a urea replaces the acetylenic linker in M-MPEP and mavoglurant,
      reveals a binding mode where the ligand is rotated by 180 degrees  compared to a
      previously proposed docking model. The need for multiple ligand structures for
      accurate GPCR structure-based drug design is demonstrated by the different
      growing vectors identified for the head groups of M-MPEP and mavoglurant and by
      the unexpected water-mediated receptor interactions of a new chemotype
      represented by fenobam. The implications of the new structures for ligand design
      are discussed, with extensive analysis of the energetics of the water networks of
      both pseudoapo and bound structures providing a new design strategy for
      allosteric modulators.

PMID- 29455527
TI  - Mechanical Division of Cell-Sized Liposomes.
AB  - Liposomes, self-assembled vesicles with a lipid-bilayer boundary similar to cell
      membranes, are extensively used in both fundamental and applied sciences.
      Manipulation of their physical properties, such as growth and division, may
      significantly expand their use as model systems in cellular and synthetic
      biology. Several approaches have been explored to controllably divide liposomes,
      such as shape transformation through temperature cycling, incorporation of
      additional lipids, and the encapsulation of protein division machinery. However,
      so far, these methods lacked control, exhibited low efficiency, and yielded
      asymmetric division in terms of volume or lipid composition. Here, we present a
      microfluidics-based strategy to realize mechanical division of cell-sized (~6
      MUm) liposomes. We use octanol-assisted liposome assembly (OLA) to produce
      liposomes on chip, which are subsequently flowed against the sharp edge of a
      wedge-shaped splitter. Upon encountering such a Y-shaped bifurcation, the
      liposomes are deformed and, remarkably, are able to divide into two stable
      daughter liposomes in just a few milliseconds. The probability of successful
      division is found to critically depend on the surface area-to-volume ratio of the
      mother liposome, which can be tuned through osmotic pressure, and to strongly
      correlate to the mother liposome size for given microchannel dimensions. The
      division process is highly symmetric (~3% size variation between the daughter
      liposomes) and is accompanied by a low leakage. This mechanical division of
      liposomes may constitute a valuable step to establish a growth-division cycle of
      synthetic cells.

PMID- 29455528
TI  - Uranyl to Uranium(IV) Conversion through Manipulation of Axial and Equatorial
      Ligands.
AB  - The controlled manipulation of the axial oxo and equatorial halide ligands in the
      uranyl dipyrrin complex, UO2Cl(L), allows the uranyl reduction potential to be
      shifted by 1.53 V into the range accessible to naturally occurring reductants
      that are present during uranium remediation and storage processes. Abstraction of
      the equatorial halide ligand to form the uranyl cation causes a 780 mV positive
      shift in the UV/UIV reduction potential. Borane functionalization of the axial
      oxo groups causes the spontaneous homolysis of the equatorial U-Cl bond and a
      further 750 mV shift of this potential. The combined effect of chloride loss and
      borane coordination to the oxo groups allows reduction of UVI to UIV by H2 or
      other very mild reductants such as Cp*2Fe. The reduction with H2 is accompanied
      by a B-C bond cleavage process in the oxo-coordinated borane.

PMID- 29455529
TI  - Differentiation of Rums Produced from Sugar Cane Juice (Rhum Agricole) from Rums
      Manufactured from Sugar Cane Molasses by a Metabolomics Approach.
AB  - A large set of volatiles (a metabolome) was isolated by SAFE distillation from 25
      high priced rums prepared from sugar cane juice (SCJ) and 26 high priced rums
      manufactured from sugar cane molasses (SCM). The volatile fractions were first
      analyzed by comprehensive two-dimensional gas chromatography time-of-flight mass
      spectrometry (GC*GC-TOF-MS), and the "comprehensive template matching
      fingerprinting" was used to extract the entire features present in the respective
      set of volatile compounds. After raw data pretreatment, chemometrics was used to
      locate marker compounds. Following, a sparse-partial-least-squares discriminant
      analysis ( sPLS-DA) and a partial-least-squares discriminant analysis (PLS-DA)
      were applied to a training data set for creating a model. The model was validated
      using leave-one-out cross validation and tested over an independent data set to
      evaluate its predictive power. The characteristic fingerprint resulted in a 100%
      correct classification of sugar cane juice rums, thus achieving the first aim of
      locating markers for these higher quality rums. Then, past-processing
      identification within the discriminant features was done to characterize 12
      significant marker compounds as 1-decanol, gamma-dodecalactone, ethyl 3
      methylbutanoate, ethyl nonanoate, 3-furancarboxaldehyde, 1-hexanol, beta-ionone,
      2- and 3-methylbutanol, methyl decanoate, 3-octanol, and 2-undecanone.
      Quantitation of eight selected markers by stable isotope dilution assays
      confirmed higher concentrations in SCJ compared to SCM and served as the final
      proof to differentiate both types of spirits.

PMID- 29455530
TI  - Pd-Doped WO3 Nanostructures as Potential Glucose Sensor with Insight from
      Electronic Structure Simulations.
AB  - Herein, we report the results of crystal-structure-dependent nonenzymatic glucose
      sensing properties of tungsten oxide (WO3) and Pd-doped WO3 nanostructures. The
      WO3 nanomaterials with orthorhombic, monoclinic, and mixed (ortho + monoclinic)
      phases were harvested by a facile hydrothermal route by varying the reaction time
      and subsequent annealing processes. Electrocatalytic activity tests of WO3
      samples revealed a 3-fold oxidation peak current enhancement in the monoclinic Pd
      doped WO3 nanobricks assembly as compared to the orthorhombic WO3 microspheres.
      Moreover, the Pd-doped WO3 showed a higher glucose-sensing performance in terms
      of the detection sensitivities of 11.4 MUA MUM-1 cm-2 (linear range: 5-55 MUM)
      and 5.6 MUA MUM-1 cm-2 (linear range: 65-375 MUM). We have also performed density
      functional theory simulations for the monoclinic WO3 and Pd-doped WO3 to
      investigate the charge-transfer and bonding mechanism of glucose on WO3 and Pd
      doped WO3 surface. As the binding energy of glucose is higher in the case of Pd
      doped WO3 as compared to bare WO3, it becomes more conducting due to enhancement
      of density of states near Fermi level; theoretically, we can predict that Pd
      doped WO3 exhibits a better charge-transfer media compared to bare WO3, resulting
      in enhanced glucose-sensing performance, which, in turn, qualitatively supports
      our experimental data. Hence, our experimental data and theoretical insight from
      the electronic structure simulations conclude that Pd-doped monoclinic WO3 is a
      potential material for the fabrication of real-time glucose sensors.

PMID- 29455531
TI  - New Insights on Hydrogen-Bond-Induced Fluorescence Quenching Mechanism of C102
      Phenol Complex via Proton Coupled Electron Transfer.
AB  - The H-bonded coumarin 102 (C102)-phenol complex has been a model system usually
      used to understand the influence of H-bonding on photophysical processes. Zhao
      and Han first showed that significant H-bond strengthening occurs in the excited
      state and proposed the possibility of fluorescence quenching in the complex via
      internal conversion from a locally excited (LE) state to a low-lying charge
      transfer (CT) state. Later, we experimentally confirmed fluorescence quenching of
      C102-phenol complex in a nonpolar solvent (cyclohexane). However, we also found
      that the existence of the low-lying CT state is ambiguous. Here, we proposed an
      alternative mechanism for the fluorescence quenching in the H-bonded complex. For
      this, we evaluate the excited state potential energy surface considering complete
      H atom-transfer from phenol to C102 along the H-bonding coordinate. Surprisingly,
      we observed two distinct minima separated by a low-energy barrier. One minimum
      corresponds to the complex with shortening of H-bond consistent with that of Zhao
      and Han. On the other hand, the second minimum, which has even lower energy than
      the first minimum, is likely to be arising from the proton-coupled electron
      transfer (PCET) process. The nature of the lowest excited state alters from LE to
      CT type at the second minimum, which may account for the fluorescence quenching
      phenomena in the system.

PMID- 29455532
TI  - Anisotropic Self-Oscillating Reaction in Liquid Crystalline Nanosheet Hydrogels.
AB  - Anisotropic chemical wave propagation of self-oscillating Belousov-Zhabotinsky
      (BZ) reaction was demonstrated in the poly( N-isopropylacrylamide) gel films
      embedded with macroscopically aligned liquid crystalline inorganic nanosheets.
      Although the average propagation rate of chemical wave v was 3.56 mm min-1 in the
      gels without nanosheets, the propagation was retarded in the gels with 1 wt % of
      nanosheets: [Formula: see text] = 1.89 mm min-1 and [Formula: see text] = 1.33 mm
      min-1 along the direction parallel and perpendicular to the nanosheet planes,
      respectively. Thus, the wave propagation is anisotropic with the anisotropy ratio
      [Formula: see text] = 1.42 in these gels and the periodic patterns formed by the
      BZ reaction were concentric ellipses, different from circles seen in isotropic
      gels. Furthermore, the propagation rate and degree of anisotropy were
      controllable by nanosheet concentration. These phenomena can be explained that
      the diffusion of molecules inside the gel is effectively hindered along the
      direction perpendicular to the nanosheet planes due to the very large aspect
      ratio of the aligned nanosheets. The present systems will be applicable for
      anisotropic self-oscillating soft actuators with one-dimensional motions as well
      as for ideal model system of BZ reactions.

PMID- 29455533
TI  - Effect of Dietary Protein Level on the Expression of Proteins in the
      Gastrointestinal Tract of Young Pigs.
AB  - The objective of this research is to investigate the effect of protein level on
      proteins expression in the gastrointestinal tract of young pigs. Eighteen piglets
      (Duroc * Landrace * Yorkshire) were weaned at 28 days of age and randomly
      assigned to three diets with 20%, 17%, and 14% CP level, and four essential amino
      acids, Lys, Met, Thr, and Trp, in three diets met the requirements of weaned
      piglets. The experimental period lasted 45 days. Compared with the control (20%
      CP level), the average daily feed intake, the average daily gain, and gain feed
      ratio of the 17% CP group did not decrease ( P > 0.05), but those of 14% CP group
      decreased ( P < 0.05). The proteomics profiles result of three tissues (gastric
      antrum, duodenum, and jejunum) showed that, compared with the control, the immune
      system, protein digestion and absorption, lipid or carbon digestion and
      absorption, etc. were up-regulated in 17% CP group, while most of them were down
      regulated in 14% CP group. Amino acids metabolism of gastric, pancreatic
      secretion of duodenum or steroid hormone biosynthesis of jejunum was down
      regulated in the 17% CP group, but the lipid metabolism was up-regulated in the
      14% CP group. Six proteins were selected for identification by Western-blot, and
      their changes had the same trend as the proteomics results. The protein level
      decreased from 20% to 17%, the growth performance was not affected, while the
      nutrient digestion and absorption or the immune function were improved, which
      implied that 17% protein level maybe benefit for nutrients absorption of pigs.

PMID- 29455534
TI  - Rate-Limiting O-O Bond Formation Pathways for Water Oxidation on Hematite
      Photoanode.
AB  - Photoelectrochemical (PEC) water oxidation has attracted heightened interest in
      solar fuel production. It is well accepted that water oxidation on hematite is
      mediated by surface trapped holes, characterized to be the high valent -Fe?O
      species. However, the mechanism of the subsequent rate-limiting O-O bond
      formation step is still a missing piece. Herein we investigate the reaction order
      of interfacial hole transfer by rate law analysis based on electrochemical
      impedance spectroscopy (EIS) measurement and probe the reaction intermediates by
      operando Fourier-transform infrared (FT-IR) spectroscopy. Distinct reaction
      orders of ~1 and ~2 were observed in near-neutral and highly alkaline
      environments, respectively. The unity rate law in near-neutral pH regions
      suggests a mechanism of water nucleophilic attack (WNA) to -Fe?O to form the O-O
      bond. Operando observation of a surface superoxide species that hydrogen bonded
      to the adjacent hydroxyl group by FT-IR further confirmed this pathway. In highly
      alkaline regions, coupling of adjacent surface trapped holes (I2M) becomes the
      dominant mechanism. While both are operable at intermediate pHs, mechanism switch
      from I2M to WNA induced by local pH decrease was observed at high photocurrent
      level. Our results highlight the significant impact of surface protonation on O-O
      bond formation pathways and oxygen evolution kinetics on hematite surfaces.

PMID- 29455535
TI  - Antioxidative Nanoparticles Significantly Enhance Therapeutic Efficacy of an
      Antibacterial Therapy against Listeria monocytogenes Infection.
AB  - Acute inflammatory conditions such as sepsis lead to fatal conditions, including
      multiple organ failure. Several treatments such as steroidal anti-inflammatory
      drugs are currently being investigated in order to decrease the blood cytokine
      level, which increases remarkably. However, any of these therapeutic treatments
      are not always reliable and effective; none have drastically improved survival
      rates, and some have mostly ended with failure. Reactive oxygen species (ROS) are
      signaling molecules responsible for the production of cytokines and chemokines
      that can mediate hyperactivation of the immune response called cytokine storm. In
      addition to the above-mentioned agents, various antioxidants have been explored
      for the removal of excess ROS during inflammation. However, the development of
      low-molecular-weight (LMW) antioxidants as therapeutic agents has been hampered
      by several issues associated with toxicity, poor pharmacokinetics, low
      bioavailability, and rapid metabolism. In the present study, we aimed to overcome
      these limitations through the use of antioxidative nanoparticles possessing
      2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) which are covalently conjugated to
      polymer. Although treatment with antioxidative nanoparticles alone did not
      eliminate bacteria, combined treatment with an antibacterial agent was found to
      significantly improve survival rate of the treated mice as compared to the
      control group. More importantly, the antioxidative nanoparticles reduced
      oxidative tissue injury caused by the bacterial infection. Thus, our findings
      highlighted the effectiveness of combination treatment with antioxidative
      nanoparticles and an antibacterial agent to prevent severe inflammation caused by
      bacterial infection.

PMID- 29455536
TI  - Resveratrol's Hidden Hand: A Route to the Optical Detection of Biomolecular
      Binding.
AB  - Resveratrol is a stilbenoid phytoalexin with promising myriad health benefits
      predominantly contributed by the trans ( E) diastereomeric form. A recent study
      has implicated the cis ( Z) diastereomer in human health. This stereoisomer binds
      with high affinity to human tyrosyl-tRNA synthetase, initiating a downstream
      cascade that promotes the expression of genes associated with the cellular stress
      response. We discovered that the nonplanar structure of the cis-resveratrol
      conformer possesses certain chiral signals in its simulated vibrational circular
      dichroism (VCD) and Raman optical activity (ROA) spectra. These features may be
      used for the optical detection of the binding event and in understanding the more
      diversified biological roles of trans-resveratrol over cis-resveratrol. We use a
      density functional theory model, which is validated against the known results for
      the E diastereomer. The Z diastereomer is significantly nonplanar and can exist
      in two helical atropisomeric forms. These forms exchange rapidly in solution, but
      only one is observed to bind with the synthetase. This suggests that the binding
      may generate an enantiomeric excess, leading to detectable changes in the
      vibrational optical activity spectra. We identify candidate features at 998,
      1649, and 1677 cm-1 in the ROA and at 1642 and 3834 cm-1 in the VCD spectra of Z
      resveratrol that may be useful for this purpose.

PMID- 29455537
TI  - Synthesis and Biophysical Characterization of an Odd-Numbered 1,3
      Diamidophospholipid.
AB  - Nanomedicine suffers from low drug delivery efficiencies. Mechanoresponsive
      vesicles could provide an alternative way to release active compounds triggered
      by the basic physics of the human body. 1,3-Diamidophospholipids with C16 tails
      proved to be an effective building block for mechanoresponsive vesicles, but
      their low main phase transition temperature prevents an effective application in
      humans. As the main phase transition temperature of a membrane depends on the
      fatty acyl chain length, we synthesized a C17 homologue of a 1,3
      diamidophospholipid: Rad-PC-Rad. The elevated main phase transition temperature
      of Rad-PC-Rad allows mechanoresponsive drug delivery at body temperature. Herein,
      we report the biophysical properties of Rad-PC-Rad monolayer and bilayer
      membranes. Rad-PC-Rad is an ideal candidate for advancing the concept of
      physically triggered drug release.

PMID- 29455538
TI  - Who Are the New Editors of Chemical Research in Toxicology?

PMID- 29455539
TI  - Immunological evaluation of chitosan nanoparticles loaded with tetanus toxoid.
AB  - OBJECTIVES: The present study was aimed at comparing tetanus toxoid (TT)-loaded
      chitosan nanoparticles with aluminum hydroxide as a common vaccine adjuvant.
      BACKGROUND: Tetanus remains to be a major public health problem. Nanoparticles
      have been extensively used as immune adjuvants. Tetanus toxoid (TT) encapsulated
      in chitosan nanoparticles is considered to be a promising tetanus vaccine
      candidate. METHODS: TT-loaded chitosan nanoparticles were prepared by the ionic
      gelation method. The nanoparticles were studied by SEM for their size and
      morphology. In vivo study was conducted to evaluate the immunity response using
      mice divided into 4 groups and injected with encapsulated toxoid. The immune
      responses were then measured using indirect ELISA. RESULTS: The purity and
      integrity of antigen were confirmed by SDS-PAGE electrophoresis. The size of
      nanoparticles was estimated at 100 nm. As a result, the IgG antibody levels were
      1.9, 1.76, and 0.87 in chitosan nanoparticles, aluminum hydroxide, and TT alone
      groups, respectively. Also, the immune responses were significantly higher in
      immunized groups compared to control groups vaccinated with free adjuvant
      vaccines (p < 0.05). CONCLUSIONS: The quality and efficacy of toxoid-loaded
      chitosan nanoparticles were reasonable. It enhanced the immune responses as much
      as aluminum hydroxide adjuvant does and thus may be a good alternative candidate
      (Tab. 1, Fig. 3, Ref. 16).

PMID- 29455540
TI  - CdS nanoparticles of different lengths induce differential responses in some of
      the liver functions of mice.
AB  - Cadmium sulfide nanoparticles (CdS NPs) are one of important nanoparticle
      materials which are widely used in photoelectric production, but their potential
      health hazard to the liver is not clear. This study is aimed at exploring the
      possible mechanisms of liver injury induced by CdS NPs. Male mice were treated
      with nanoparticles of 110-130 nm and 80-100 nm cadmium sulfide. The main methods
      were based on detecting the vigor of superoxide dismutase (SOD) and glutathione
      (GSH), and content of malondialdehyde (MDA) in both blood and liver tissues as
      well as on observing the pathological changes in liver tissue. CdS NPs suppressed
      the activity of SOD and GSH, and increased the serum MDA content (p < 0.05); both
      effects were observed together in liver tissues of 80-100 nm group (p < 0.05) and
      were accompanied by an obviously inflammatory response. CdS NPs induced oxidative
      damage and inflammatory response in liver tissue, which may be an underlying
      mechanism for its pulmonary toxicity. Additionally, the toxicity of CdS NPs was
      closely related to the size of nanoparticles. Pathological results showed that
      the hepatotoxicity of shorter CdS NPs is greater than that of longer CdS NPs
      (Tab. 6, Fig. 3, Ref. 20).

PMID- 29455541
TI  - The efficacy of ozone therapy in neonatal rats with hypoxic ischemic brain
      injury.
AB  - OBJECTIVES: This study is aimed to determine the effect of ozone therapy in
      neonatal rats with experimentally induced hypoxic ischemic brain injury (HIBI).
      METHODS: The study included 7-d-old male Wistar rats that were randomized to the
      sham, control, ozone 1, and ozone 2 groups. All rats except those in the sham
      group were kept in a hypoxia chamber, and then the rats in the control group were
      given 0.5 mL of saline. Those in the ozone 1 group were given ozone 1 mg kg-1
      intraperitoneally, and those in the ozone 2 group were given ozone 2 mg kg-1
      intraperitoneally. RESULTS: There were significantly fewer apoptotic neurons in
      the right hemispheres of the rats in the ozone 1 and ozone 2 groups than in the
      control group (p < 0.001 and p < 0.001, respectively). There were significantly
      fewer apoptotic neurons in the right hemispheres of the rats in the ozone 2 group
      than in the ozone 1 group (p < 0.001). Morris Water Maze (MWM) test results were
      similar in the ozone 2 and sham groups. CONCLUSIONS: The present study's findings
      show that ozone therapy reduced neuronal apoptosis and improved cognitive
      function in neonatal rats with experimentally induced HIBI (Tab. 2, Ref. 30).

PMID- 29455542
TI  - Neuroprotective effects of high-dose human albumin against traumatic spinal cord
      injury in rats.
AB  - BACKGROUND AND OBJECTIVES: Human serum albumin (HA) is a unique multifunctional
      protein with neuroprotective properties. We aimed to delineate the mechanisms of
      HA-induced neuroprotection, supresses inflammatory response and lipid
      peroxidation after spinal cord injury (SCI). METHODS AND STUDY DESIGN: Adult
      female Wistar rats weighing 210-250 g were used for the study. The rats were
      randomly and blindly allocated into five groups. The one-way analysis of variance
      (ANOVA) for parametric data and Shapiro-Wilk test was used for evaluating the
      normal distribution of the variables. Kruskal-Wallis for nonparametric data was
      used to compare groups. Electron and light microscopies were used to demonstrate
      ultrastructural changes in spinal cord. RESULTS: The HA group was significantly
      different from all the other groups (p < 0.05). Both MPSS and HA treatments
      decreased the MPO significantly. HA treatment decreased the lipid peroxidation.
      HA treatment prevented the worsening of clinical results. In the HA treatment
      group, the ultrastructure was protected significantly. The neuronal bodies and
      axonal structures were normal except for some limited edematous spaces.
      CONCLUSIONS: HA improves early clinical results, protects spinal cord
      ultrastructure, and decreases MPO and LPO levels after spinal cord contusion
      injury (Tab. 3, Fig. 3, Ref. 39).

PMID- 29455543
TI  - Effect of leucine on NF-kappaB pathway in liver regeneration after partial
      hepatectomy in rats, as determined by miniarray analysis.
AB  - BACKGROUND: Although some amino acids are recognized to have favorable effects on
      the liver regeneration after partial hepatectomy (PH), molecular mechanisms
      underlying these effects are barely known. OBJECTIVE: Our study was aimed to
      investigate the effects of valine, glutamine, and leucine amino acids on PH
      induced NF-kappaB signal pathway. The research team studied Leucine in a rat
      model in vivo. The study took place in the medical and surgical experimental
      research center at the Eskisehir Osmangazi University in Eskisehir, Turkey. The
      animals were Wistar albino male rats. RESULTS: Group I, the sham group, was
      administered phosphate buffered saline (PBS) after laparotomy. After 70 % PH
      procedure, group II, III, IV, and V received single intraperitoneal doses of PBS,
      valine, glutamine, and leucine amino acids, respectively. At hour 6 after PH,
      expressions of 88 genes involving in NF-kappaB signal pathway were examined by RT
      PCR mini array method in the liver tissue specimen. Fold values below 0.5 and
      above 2 were regarded as significant. CONCLUSIONS: Our results suggested that
      valine, glutamine, and leucine amino acids may alter expressions of the genes of
      NF-kappaB signal pathway. In addition, among these amino acids, glutamine and
      valine proved to be much more effective on NF-kappaB signal pathway after the PH
      (Tab. 1, Ref. 41).

PMID- 29455544
TI  - Heart failure affects liver morphology and function. What are the clinical
      implications?
AB  - Liver dysfunction in heart failure is common and usually clinically significant,
      especially in patients with advanced or severe acute heart failure. Lesions are
      caused by an impaired hepatic circulation due to congestion and hypoperfusion.
      Congestive lesions are more common and typically manifested by painful
      hepatomegaly and increased direct bilirubin and alkaline phosphatase. The
      inferior vena cava and hepatic veins are usually dilated. Congestive lesions are
      characterized by dilatation of the central vein with fibrotic changes in the
      surrounding areas on histological examination. Isolated ischaemic lesions are
      rare and occur due to severe and prolonged ineffective perfusion, often
      accompanied by hypoxemia. Ineffective perfusion is reflected by an increase in
      total bilirubin and significantly increased transaminase levels. The prognosis of
      ischaemic lesions without an adequate treatment of the cause of hypoperfusion is
      poor. Increased levels of bilirubin and liver function tests, as well as signs of
      impaired liver proteosynthetic function, are associated with a poor prognosis.
      Knowledge of the phenotypes of hepatic lesions in heart failure is important to
      select the appropriate treatment for an acute decompensation. Changes in
      biochemical markers, hepatic perfusion or stiffness of the liver can be used to
      evaluate the effectiveness of diuretic treatment and achieve euvolemic status in
      the patients with heart failure (Tab. 1, Fig. 3, Ref. 28).

PMID- 29455545
TI  - Role of autophagy in the progress of coronary total occlusion.
AB  - OBJECTIVE: In this study, we measured the level of autophagy enzyme in patients
      with coronary artery disease (CAD) and investigated whether the role of autophagy
      existed in the progress of coronary collateral and coronary total occlusion (TO).
      METHODS: Overall, 115 participants were included in this study. They were divided
      into the three groups: group 1: patients had chronic TO (n=49); group 2: patients
      had acute TO such as myocardial infarction (n=36); and group 3: participants were
      normal controls (n=30). The enzyme-linked immunosorbent assay (ELISA) kit for
      autophagy-related protein 5 (ATG5) in the plasma was studied for these three
      groups. RESULTS: Autophagy levels were significantly different between the groups
      (13.7+/-5.3, 11.7+/-3.4, and 7.5+/-3 ng/mL, respectively; p<0.001). In the
      subgroup analysis, we found significant positive correlations between the level
      of autophagy and Rentrop score in the Group 1 (r=0.463, p<0.001). CONCLUSION: In
      the present study, autophagy levels were higher in the patients with CAD than in
      healthy controls. In addition, serum autophagy levels showed a significant
      positive correlation with the Rentrop score. An increased autophagy level may be
      considered an important activator and marker of the atherosclerotic inflammatory
      process in CAD (Tab. 1, Fig. 2, Ref. 20).

PMID- 29455546
TI  - Effects of complete water fasting and regeneration diet on kidney function,
      oxidative stress and antioxidants.
AB  - OBJECTIVE: The aim of the study was to observe the influence of 11-days complete
      water fasting (WF) and regeneration diet (RD) on renal function, body weight,
      blood pressure and oxidative stress. BACKGROUND: Therapeutic WF is considered a
      healing method. METHODS: Ten volunteers drank only water for 11 days, followed by
      RD for the next 11 days. Data on body weight, blood pressure, kidney functions,
      antioxidants, lipid peroxidation, cholesterols, triacylglycerols and selected
      biochemical parameters were obtained. RESULTS: WF increased uric acid and
      creatinine and decreased glomerular filtration rate. After RD, the parameters
      were comparable to baseline values. Urea was not affected. Lipid peroxidation
      (TBARS) decreased and maintained stable after RD. Fasting decreased alpha
      tocopherol and increased gamma-tocopherol, no significant changes were found
      after RD. Coenzyme Q10 decreased after RD. HDL-cholesterol decreased in WF. Total
      and LDL-cholesterol decreased after RD. Other biochemical parameters were within
      the range of reference values. CONCLUSIONS: The effect of the complete fasting on
      kidney function was manifested by hyperuricemia. Renal function was slightly
      decreased, however maintained within the reference values. After RD, it returned
      to baseline values. The positive effect of the complete water fasting was in the
      reduction of oxidative stress, body weight and blood pressure (Tab. 3, Ref. 25).

PMID- 29455547
TI  - Evaluation of fractalkine (FKN) and secreted frizzled-related protein 4 (SFRP-4)
      serum levels in patients with prediabetes and type 2 diabetes.
AB  - OBJECTIVE: The objective of this study is to compare serum levels of FKN and SFRP
      4 in patients with normal glucose tolerance (NGT), impaired glucose tolerance
      (IGT), and type 2 diabetes mellitus (T2DM). METHODS: A total of 152 patients
      presented to the endocrinology outpatient clinic of our hospital were included in
      the study. Eighty-two patients with a history of T2DM were assigned to the T2DM
      group. IGT (n = 34) and NGT (n = 36) groups included the patients who received
      oral glucose tolerance test outcomes. RESULTS: Serum FKN levels were
      significantly higher in the IGT and T2DM groups compared to the NGT group (p <
      0.001 and p < 0.001, respectively). Serum SFRP-4 levels were significantly higher
      in the T2DM group compared to the IGT and NGT groups (p = 0.001 and p = 0.004,
      respectively). A significant correlation was observed between FKN and fasting
      glucose levels. SFRP-4 was significantly correlated with fasting glucose, HbA1c,
      and triglyceride levels. CONCLUSION: To our knowledge, increased FKN levels in
      patients with IGT were demonstrated for the first time in this study. The results
      of our study support the opinion that FKN and SFRP-4 may contribute to the
      pathogenesis of T2DM (Tab. 1, Fig. 3, Ref. 23).

PMID- 29455548
TI  - The effects of smoking on neutrophil/lymphocyte, platelet/ /lymphocyte ratios.
AB  - OBJECTIVE: The aim of this study was to compare the Neutrophil to Lymphocyte
      ratio (NLR), Platelet to Lymphocyte ratio (PLR) and Mean Platelet Volume to
      Platelet (MPV/Plt) ratio of smokers and non-smokers. METHODS: Two hundred smokers
      and two hundred non-smoking healthy volunteers were enrolled in this study.
      Sociodemographic data and hematologic parameters of all patients were recorded.
      NLR, PLR and MPV/Plt ratios were calculated. RESULTS: The mean age of the case
      group was 35.88 +/- 10.56 and the mean age of the control group was 38.97 +/-
      10.56. 80 % (n = 160) of the smokers were male and 20 % (n = 40) were female.
      27.5 % (n = 55) of the control group were male and 72.5 % (n = 145) were female.
      The smoker group had higher NLR and MPV/Plt ratio (p < 0.05). PLR was
      significantly higher for the non-smoker group (p < 0.05). CONCLUSION: As a result
      of our study, an increase in the NLR which is used as a systemic inflammatory
      marker, a decrease in the PLR and an increase in the MPV/Plt ratio which
      indicates thromboembolism risk were found for the smoker group (Tab. 3, Ref. 32).

PMID- 29455549
TI  - Multiple endocrine neoplasia 2A (MEN 2A) syndrome.
AB  - INTRODUCTION: In the MEN 2A syndrome, which is the most common of the three types
      of MEN, three endocrine systems are affected simultaneously or subsequently by
      the development of tumours manifested by medullary thyroid gland carcinoma,
      pheochromocytoma (often bilateral) and hyperparathyroidism. MATERIAL AND METHODS:
      27 patients from 3 families affected by MEN 2A syndrome were examined clinically
      (by detecting the effects of catecholamine overproduction), biochemically
      (screening for metanephrine and normetanephrine in the serum), visualization (CT,
      MRI, MIBG, PET CT) and some of them also genetically (DNA fragment analysis
      obtained by PCR amplification). RESULTS: Familial incidence of pheochromocytoma
      was confirmed in 10 patients (4 males, 5 females and one girl) aged 6 to 54 years
      (average 22.8 years) . In 5 patients, the pheochromocytoma occurred on both
      sides, in one patient, with genetically proved MEN 2A syndrome, only one adrenal
      gland was affected by pheochromocytoma. In 10 patients, mutations were detected
      in the exon 10, 11 and 16 RET of the proto-oncogene in the centromeric region of
      the 10th chromosome. After proper preparation, 5 patients underwent bilateral
      adrenalectomy (unilateral adrenalectomy in one patient). Histological examination
      of the removed tumours in all cases excluded the malignant pheochromocytoma.The
      first of the operated patients (54 yr) died after surgery for cardiovascular
      failure. Others have lived 5 to 15 years after bilateral adrenalectomy without
      signs of local recurrence of the disease, and have no clinical signs of over
      production of catecholamines. CONCLUSION: Bilateral pheochromocytoma and thyroid
      carcinoma are indications for detailed clinical and genetic examination of all
      family members. Bilateral adrenalectomy with lifetime supplementation of adrenal
      hormones is indicated in symptomatic patients and/or patients asymptomatic with
      tumours larger than 3 cm in diameter (Tab. 1, Fig. 11, Schema 1, Ref. 31).

PMID- 29455550
TI  - The association of HBV with immigrant subjects.

PMID- 29455551
TI  - Effects of 5-Aza-2'-deoxycytidine (decitabine) on gene expression.
AB  - 5-Aza-2'-deoxycytidine (AzaD), also known as Decitabine, is a deoxycytidine
      analog that is typically used to activate methylated and silenced genes by
      promoter demethylation. However, a survey of the scientific literature indicates
      that promoter demethylation may not be the only (or, indeed, the major) mechanism
      by which AzaD affects gene expression. Regulation of gene expression by AzaD can
      occur in several ways, including some that are independent of DNA demethylation.
      Results from several studies indicate that the effect of AzaD on gene expression
      is highly context-dependent and can differ for the same gene under different
      environmental settings. This may, in part, be due to the nature of the silencing
      mechanism(s) involved - DNA methylation, repressive histone modifications, or a
      combination of both. The varied effects of AzaD on such context-dependent
      regulation of gene expression may underlie some of the diverse responses
      exhibited by patients undergoing AzaD therapy. In this review, we describe the
      salient properties of AzaD with particular emphasis on its diverse effects on
      gene expression, aspects that have barely been discussed in most reviews of this
      interesting drug.

PMID- 29455552
TI  - In honour of Professor Leaf Huang, recipient of the Journal of Drug Targeting's
      life-time achievement award for 2018.

PMID- 29455553
TI  - Correlates of missed clinic visits among youth living with HIV.
AB  - Youth living with HIV (YLH) have significant problems with attending their
      medical appointments. Poor attendance, consequently, predicts viral non
      suppression and other negative health outcomes. To identity targets of
      intervention, this cross-sectional study examined correlates of past-year missed
      clinic visits among YLH (N = 2125) attending HIV clinics in the United States and
      Puerto Rico. Thirty-six percent of YLH missed two or more visits in the past
      year. Several factors were associated with missed visits in our regression model.
      Among sociodemographic characteristics and HIV disclosure status, females
      (adjusted odds ratio [OR] = 1.63, compared to males), Black YLH or YLH of mixed
      racial heritage (AORs = 1.76, 1.71, respectively, compared to White YLH), YLH
      with an unknown route of infection (AOR = 1.86, compared to YLH with perinatal
      infection), and YLH endorsing HIV disclosure (AOR = 1.37, compared to YLH not
      endorsing disclosure) were at greater risk for missed visits. Among behavioral
      health risks, YLH who endorsed marijuana use (AOR = 1.42), frequent other drug
      use (AOR = 1.60), or a history of incarceration (AOR = 1.27) had greater odds of
      missed visits than youth not endorsing these risks. Finally, two social-cognitive
      resources emerged as protective factors: adherence self-efficacy (AOR = .28) and
      social support (AOR = .88). We discuss how providers working with YLH can improve
      this population's retention outcomes.

PMID- 29455555
TI  - Employment status is related to sleep problems in adults with autism spectrum
      disorder and no comorbid intellectual impairment.
AB  - Both sleep problems and unemployment are common in adults with autism spectrum
      disorder; however, little research has explored this relationship in this
      population. This study aimed to explore factors that may be associated with the
      presence of an International Classification of Sleep Disorders-Third Edition
      defined sleep disorder in adults with autism spectrum disorder (IQ > 80). A total
      of 36 adults with autism spectrum disorder and 36 controls were included in the
      study. Participants completed a 14-day actigraphy assessment and questionnaire
      battery. Overall, 20 adults with autism spectrum disorder met the International
      Classification of Sleep Disorders-Third Edition criteria for insomnia and/or a
      circadian rhythm sleep-wake disorder, while only 4 controls met criteria for
      these disorders. Adults with autism spectrum disorder and an International
      Classification of Sleep Disorders-Third Edition sleep disorder had higher scores
      on the Pittsburgh Sleep Quality Index and were more likely to be unemployed
      compared to adults with autism spectrum disorder and no sleep disorder. The
      findings demonstrate, for the first time, that sleep problems are associated with
      unemployment in adults with autism spectrum disorder. Further research exploring
      the direction of this effect is required; sleep problems that have developed
      during adolescence make attainment of employment for those with autism spectrum
      disorder difficult, or unemployment results in less restrictions required for
      optimal and appropriate sleep timing.

PMID- 29455554
TI  - Synthesis, antitumour and antioxidant activities of novel alpha,beta-unsaturated
      ketones and related heterocyclic analogues: EGFR inhibition and molecular
      modelling study.
AB  - New alpha,beta-unsaturated ketones 4a,b; 5a-c; and 6a,b; as well as 4-H pyran 7;
      pyrazoline 8a,b; isoxazoline 9; pyridine 10-11; and quinoline-4-carboxylic acid
      12a,b derivatives were synthesized and evaluated for in vitro antitumour activity
      against HepG2, MCF-7, HeLa, and PC-3 cancer cell lines. Antioxidant activity was
      investigated by the ability of these compounds to scavenge the 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS*+). Compounds 6a, 6b,
      7, and 8b exhibited potent antitumour activities against all tested cell lines
      with [IC50] ?5.5-18.1 uMU), in addition to significantly high ABTS*+ scavenging
      activities. In vitro EGFR kinase assay for 6a, 6b, 7, and 8b as the most potent
      antitumour compounds showed that; compounds 6b, and 7 exhibited worthy EGFR
      inhibition activity with IC50 values of 0.56 and 1.6 uM, respectively, while
      compounds 6a and 8b showed good inhibition activity with IC50 values of 4.66 and
      2.16 uM, respectively, compared with sorafenib reference drug (IC50 = 1.28 uM).
      Molecular modelling studies for compounds 6b, 7, and 8b were conducted to exhibit
      the binding mode towards EGFR kinase, which showed similar interaction with
      erlotinib.

PMID- 29455556
TI  - Conventional vs Computer-Assisted Stereoscopic Ultrasound Needle Guidance for
      Renal Access: A Randomized Crossover Bench-Top Trial.
AB  - PURPOSE: Ultrasound (US) guidance during renal access and mass biopsy reduces
      radiation exposure, but can be technically challenging. A needle guidance system
      might simplify these procedures. The purpose of this randomized crossover trial
      was to compare conventional and computer-assisted US needle guidance systems for
      renal access and mass biopsy. MATERIALS AND METHODS: Seventy-one subjects were
      randomized to perform renal access or mass biopsy on a phantom using conventional
      and computer-assisted US guidance in a crossover study design. The primary
      outcome was success rate including subgroup analysis by experience level.
      Secondary outcomes included total procedure time, time to hit target, number of
      course corrections, and total punctures. In addition, subjective preferences of
      participants were also collected. RESULTS: Procedure success rate was higher with
      the computer-assisted US than with conventional US for both novice (98.0% (48/49)
      vs 81.6% (40/49); p < 0.001) and experienced US users (100% (22/22) vs 81.8%
      (18/22); p < 0.001). Computer-assisted US significantly shortened the total
      procedure time (94.0 seconds vs 192.9 seconds; p <= 0.001), time required to hit
      the target (62.5 seconds vs 121.6 seconds; p <= 0.001), and the number of course
      corrections (0.56 vs 2.89; p < 0.001) compared with conventional US. Computer
      assisted US did not significantly reduce the number of needle punctures (1.75 vs
      2.39; p = 0.132). Seventy-three percent of subjects preferred the computer
      assisted US system. CONCLUSION: A computer-assisted needle guidance system
      increases effective US targeting for renal access and mass biopsy for novice and
      experienced users.

PMID- 29455557
TI  - The effects of rutin on cisplatin induced oxidative retinal and optic nerve
      injury: an experimental study.
AB  - AIM: To determine the role of rutin in prevention of cisplatin induced retinal
      and optic nerve injury in an experimental study. MATERIALS AND METHODS: Totally
      18 albino Wistar male rats were assigned into three groups, as follows: healthy
      controls (HC group), only cisplatin administered group for 14 days (CIS group),
      and rutin + cisplatin administered group for 14 days (RC group). Blood samples
      were obtained from animals just before the scarification. Serum malondialdehyde
      (MDA), myeloperoxidase (MPO), total glutathione (tGSH), superoxide dismutase
      (SOD), interleukin 1 beta (IL-1beta) and tumour necrosis factor alpha (TNF-alpha)
      levels were investigated. The eyes were enucleated for histopathological
      evaluations of retina and optic nerve. RESULTS: MDA, MPO, IL-1beta and TNF-alpha
      levels were statistically significantly higher (p < 0.001) in CIS group compared
      with other two groups while tGSH and SOD levels were statistically significantly
      lower (p < 0.001). Regarding these parameters, in CIS group MDA, MPO, IL1beta and
      TNF-alpha levels were statistically significantly increased with cisplatin
      administration and giving rutin concomitantly with cisplatin prevented this
      increase. On the other hand, tGSH and SOD levels were statistically significantly
      decreased with cisplatin administration and giving rutin concomitantly with
      cisplatin prevented this decrease. In qualitative analyses of histopathological
      findings of retina and optic nerve; the results of RC group were similar with the
      results of healthy controls; but there was statistically significant differences
      between CIS group and other two groups (p < 0.001). CONCLUSIONS: Concomitant
      rutin administration may prevent the detrimental effects of cisplatin on lipid
      peroxidation, oxidative stress and inflammation markers and may also avert the
      histopathological damage on retina and optic nerve. Further studies are warranted
      to determine the effects of cisplatin and rutin on eye.

PMID- 29455558
TI  - Investigational immunosuppressants in early-stage clinical trials for the
      treatment of multiple sclerosis.
AB  - INTRODUCTION: Multiple sclerosis (MS) is a chronic demyelinating disease of the
      central nervous system with an immune mediated pathogenesis. Several therapies
      that suppress or modulate diverse immune system functions have been used for
      decades with the aim of modifying the disease course. However, these treatments
      have either limited efficacy or potentially serious adverse events that prevent
      first-line use on large scale. Areas covered: The aim of the present article is
      to review ongoing or recently completed clinical trials investigating
      immunosuppressive drugs for MS. The websites clinicaltrials.gov,
      clinicaltrialsregister.eu, and pubmed.gov were searched for phase 1, phase 2, and
      phase 3 trials starting from 2012. Twelve drugs were identified, including seven
      monoclonal antibodies and five small molecules. Expert opinion: Current or
      recently completed trials of immunosuppressants for MS are mainly proof-of
      concept studies enrolling patients with relapsing disease and using efficacy
      endpoints based on magnetic resonance imaging measures of inflammatory activity.
      Sphingosine 1-phosphate receptor modulators and B-cell depleting therapies
      represent the most commonly investigated drugs, suggesting that mechanisms of
      action that have already shown promise for MS treatment are being exploited to
      find new therapies with improved safety, tolerability, and convenience of dosing.
      Clinical trials of immunosuppressants for progressive MS are largely lacking.

PMID- 29455560
TI  - A celebration of Professor Leaf Huang's contribution to the field of drug
      delivery and his lifetime achievement award.

PMID- 29455559
TI  - Proceedings of the first Italian conference on thyroid minimally invasive
      treatments and foundation of the Italian research group for thyroid minimally
      invasive procedures.

PMID- 29455561
TI  - Rates of latent tuberculosis infection in patients treated with TNF inhibitors
      for psoriasis: a retrospective chart review.
AB  - BACKGROUND: Although tuberculosis screening guidelines for psoriasis patients on
      TNF inhibitors exist, few studies have reported the prevalence of latent
      tuberculosis infection (LTBI) and conversion rates in this population. OBJECTIVE:
      To determine the incidence of LTBI and active tuberculosis in patients with
      psoriasis receiving TNF inhibitor therapy. METHODS: A total of 138 patients were
      included in our retrospective study of patients treated from September 2004 to
      September 2017. Tuberculin skin test was considered positive with an induration
      of greater than 5 mm. History of Bacillus Calmette-Guerin vaccination, follow-up
      tests and prophylaxis were recorded. RESULTS: Among 99 biologic-naive patients,
      14 had LTBI before starting biologic therapy and five developed LTBI during TNF
      inhibitor therapy. One biologic-naive patient developed LTBI, then active
      tuberculosis. Among 39 non-biologic-naive patients, three had LTBI before
      starting any biologic therapy, and one developed LTBI during treatment.
      LIMITATIONS: Limitations include small sample size and limited information
      documented in the medical chart. CONCLUSIONS: LTBI appears to be prevalent among
      psoriasis patients. Screening for LTBI in patients on biologics may reduce risk
      of active tuberculosis; however, current methods may not be fully effective.
      Clinicians may need to use other tools including risk factor assessment to fully
      evaluate risk.

PMID- 29455562
TI  - Spatiotemporal Characteristics of the HIV-1 CRF02_AG/CRF63_02A1 Epidemic in
      Russia and Central Asia.
AB  - Eastern European countries, including Russia, Ukraine, and other former Soviet
      Union (FSU) countries, have experienced a human immunodeficiency virus (HIV)
      epidemic spreading mostly among people who inject drugs (PWID). We aimed to
      investigate the origin and the dispersal patterns of HIV-1 CRF02_AG in Russia and
      other FSU countries. We studied 136 CRF02_AG sequences originating from Russia,
      and FSU countries along with a globally sampled dataset of 3,580 CRF02_AG
      sequences. Maximum-likelihood phylogeny reconstruction with bootstrap evaluation
      was conducted in RAxML. Bayesian phylogeographic analysis was performed in BEAST
      v1.8 using the discrete trait model. We found that all CRF02_AG sequences from
      Russia and other FSU countries formed a single monophyletic cluster within
      CRF02_AG radiation. The Russian/FSU clade was classified as CRF63_02A1. Sequences
      from the FSU countries clustered further within distinct subclades (two from
      Russia, three from Uzbekistan, and one Kazakhstan) according to the geographic
      origin of sampling. Molecular clock analysis revealed that the time to the most
      recent common ancestor (tMRCA) of the CRF63_02A1 epidemic was in 1996 [95% higher
      posterior density (95% HPD): 1992-1999], while for the two Russian subclades,
      tMRCA was estimated in 2003 (95% HPD: 2001-2004) and in 2007 (95% HPD: 2005
      2008). Phylogeographic analysis suggested that the potential origin of the
      epidemic was in Uzbekistan. Early dispersal of CRF63_02A1 occurred in Kazakhstan
      and Uzbekistan and thereafter the epidemic spread to Russia. Notably, spillover
      transmissions to Russia kept occurring from both countries. Previous studies have
      shown that Russia and Ukraine have provided the source for the PWID-driven, HIV-1
      subtype-A epidemic, spreading across the FSU countries (AFSU). In great contrast,
      CRF63_02A1 established an epidemic in central Asia (Uzbekistan and Kazakhstan),
      from where it subsequently disseminated to Russia. Our study suggests that cross
      border transmissions among PWID occur bidirectionally between Russian and other
      FSU populations. These results are of public health importance and suggest that
      prevention actions have to be reinforced in this area to assist the management of
      high-risk practices.

PMID- 29455563
TI  - Editorial Comment on: Isolated Red Patches Seen During Endoscopic Surveillance of
      Bladder Cancer: Incidence of Malignancy and When Should We Biopsy? by Nkwam et
      al.

PMID- 29455564
TI  - Measurement uncertainty of platelet concentration using the Sysmex XN automated
      hematology analyzer.
AB  - We estimated the measurement uncertainty (MU) of platelet concentration measured
      using the Sysmex XN system with two reference platelet counting methods described
      by DIN 58932-5 (PTB method) and the International Council for Standardization in
      Haematology (ICSH method). Ten blood samples were used to estimate and compare
      the MU of the XN system, and 30 samples were used to compare the methods. The
      standard uncertainty of the reference method was significantly higher for the
      ICSH method; the PTB method showed higher platelet concentrations than the ICSH
      method. When applying different methods with the XN system, optic counting showed
      higher MU compared to the other methods. There was good correlation among the two
      reference methods and three automated platelet-counting methods. We evaluated the
      MU in platelet concentrations measured using an automated hematology analyzer.
      Our results suggest that using the PTB method for calculating MU of the automated
      hematology analyzer is superior to the ICSH method because of its lower standard
      uncertainty.

PMID- 29455565
TI  - Pulsed dye laser versus intense pulsed light in melasma: a split-face comparative
      study.
AB  - BACKGROUND: Recent reports suggest that melasma may have a vascular component.
      Vascular targeting lasers and light treatment can be a therapeutic option that
      will provide benefits to the patients. OBJECTIVES: To compare the efficacy and
      tolerability of pulsed dye laser (PDL) and intense pulsed light in treatment of
      melasma. PATIENTS AND METHODS: Twenty-eight Egyptian female patients with melasma
      were treated with PDL on the right hemiface (Group A) and with the intense pulsed
      light on the left hemiface (Group B). Clinical assessment was performed according
      to the hemifacial modified Melasma Area and Severity Index score (mMASI). Tissue
      biopsies were taken from patients for immunohistochemical staining with vascular
      endothelial growth factor (VEGF) antibody. RESULTS: The hemifacial mMASI score
      was significantly reduced after treatment in studied groups with no statistically
      significant difference. Intense pulsed light (IPL) group showed higher efficacy
      of treatment than PDL group in the epidermal melasma and in melasma lesions which
      had a vascular component. The expression level and intensity score of VEGF were
      significantly reduced after treatment in both groups. CONCLUSIONS: Both PDL and
      IPL were effective and safe treatment modalities for lightening of melasma. VEGF
      can be proved as a possible mechanism underlying the action of both PDL and IPL
      on melasma.

PMID- 29455566
TI  - 'He supported me 100%': Mexican-immigrant fathers, daughters, and adolescent
      sexual health.
AB  - OBJECTIVE: First and second generation Mexican-origin adolescents in the U.S.
      face social and economic disadvantage and sexual health disparities. Although
      fathers can support child and adolescent development, the literature has
      portrayed Mexican-origin immigrant fathers as emotionally distant and sexist.
      This study aims to treat migration as a social determinant of health to examine
      father-daughter relationships and adolescent sexual health in Mexican-origin
      immigrant families. METHODS: Integrating qualitative data from life history
      interviews with 21 Mexican-origin young women in immigrant families with
      quantitative data on first and second generation Mexican-origin young women in
      the National Longitudinal Study of Adolescent to Adult Health, this study
      describes father-daughter relationships, examines the association between father
      daughter relationships and daughters' early sexual initiation, and considers the
      impact of migration on the father-daughter relationship and sexual health among
      Mexican-origin young women. RESULTS: Qualitative data identify four types of
      father-daughter relationships: 'good,' hostile, distant, and conflicted.
      Supporting the qualitative patterns, quantitative data find that positive or
      'good' father-daughter relationship quality is significantly associated with
      reduced risk of early sexual initiation. Importantly, father-daughter separation
      across borders and economic inequality facing immigrant families is associated
      with hostile or distant father-daughter relationship quality and increased risk
      of early sexual initiation. CONCLUSIONS: Reports of good father-daughter
      relationships are common and may protect against early sexual initiation in
      Mexican-origin immigrant families. Policies that keep families together and
      reduce economic inequality among immigrants may also reduce sexual health
      disparities among immigrant adolescents.

PMID- 29455567
TI  - Apixaban or Rivaroxaban Versus Warfarin for Treatment of Submassive Pulmonary
      Embolism After Catheter-Directed Thrombolysis.
AB  - BACKGROUND: Little data exist on the use of direct oral anticoagulant (DOAC)
      factor Xa inhibitors for submassive pulmonary embolism (PE) after catheter
      directed thrombolysis (CDT). The objective of this evaluation was to determine
      whether the transition from parenteral anticoagulation to DOACs for submassive PE
      after CDT would decrease hospital length of stay (LOS) compared to warfarin.
      METHODS: A retrospective review of patients diagnosed with submassive PE who
      underwent CDT was conducted from January 1, 2012, to February 28, 2017. Hospital
      LOS and major and minor bleeding events were recorded during hospitalization and
      at 90 days. RESULTS: Sixty-two patients met the inclusion criteria, 36 in
      warfarin group and 26 in the DOAC group. Overall, patients receiving rivaroxaban
      or apixaban had a shorter median hospital LOS compared to warfarin (4.0 vs 6.1
      days, P = .002). In the multivariate regression analysis, administration of DOAC
      was an independent predictor of decreased hospital LOS, beta: -2.1, 95%
      confidence interval (-3.5 to -0.7). CONCLUSION: Among patients with submassive
      PE, initiation of a DOAC shortly after CDT may result in a decreased hospital LOS
      compared to parenterally bridged warfarin.

PMID- 29455568
TI  - Effectiveness and Safety of LMWH Treatment in Patients With Cancer Diagnosed With
      Non-High-Risk Venous Thromboembolism: Turkish Observational Study (TREBECA).
AB  - We compared the efficacy and safety of low-molecular-weight heparins (LMWHs) in
      patients with cancer who are at low risk of venous thromboembolism (VTE).
      Patients were treated by medical oncologists in Turkey at 15 sites, where they
      were enrolled and followed up for a period of 12 months. Due to the study design,
      there was no specific treatment protocol for LMWH. Primary end points were
      efficacy and the time to change in VTE status. Of the included 250 patients, 239
      (95.6%), 176 (70.4%), 130 (52.0%), and 91 (36.4%) completed their day 15, month
      3, month 6, and month 12 visits, respectively. Number of patients treated with
      enoxaparin, bemiparin, and tinzaparin were 133, 112, and 5, respectively.
      Anticoagulant therapy provoked thrombus resolution in 1.2% and 12.7% of patients
      using enoxaparin and bemiparin, respectively ( P = .004). Thrombus resolution was
      observed in 81 more patients at month 3 visit. This ratio was 35 (40.2%) of 87
      and 46 (54.1%) of 85 patients administered enoxaparin and bemiparin at the third
      visit, respectively ( P = .038). Thrombus resolution was observed in 21 more
      patients during month 6 visit. This ratio was 5 (7.7%) of 65 and 15 (23.4%) of 64
      patients administered enoxaparin and bemiparin at the fourth visit, respectively
      ( P = .022). The LMWH was discontinued in only 2 patients due to gastrointestinal
      bleeding. This pioneering study shows bemiparin is more effective than enoxaparin
      in thrombosis resolution and has a similar tolerability profile.

PMID- 29455569
TI  - Repetition Is the Feature Behind the Attentional Bias for Recognizing Threatening
      Patterns.
AB  - Animals attend to what is relevant in order to behave in an effective manner and
      succeed in their environments. In several nonhuman species, there is an evolved
      bias for attending to patterns indicative of threats in the natural environment
      such as dangerous animals. Because skins of many dangerous animals are typically
      repetitive, we propose that repetition is the key feature enabling recognition of
      evolutionarily important threats. The current study consists of two experiments
      where we measured participants' reactions to pictures of male and female models
      wearing clothing of various repeating (leopard skin, snakeskin, and floral print)
      and nonrepeating (camouflage, shiny, and plain) patterns. In Experiment 1, when
      models wearing patterns were presented side by side with total fixation duration
      as the measure, the repeating floral pattern was the most provocative, with total
      fixation duration significantly longer than all other patterns. Leopard and
      snakeskin patterns had total fixation durations that were significantly longer
      than the plain pattern. In Experiment 2, we employed a visual-search task where
      participants were required to find models wearing the various patterns in a
      setting of a crowded airport terminal. Participants detected leopard skin pattern
      and repetitive floral pattern significantly faster than two of the nonpatterned
      clothing styles. Our experimental findings support the hypothesis that repetition
      of specific visual features might facilitate target detection, especially those
      characterizing evolutionary important threats. Our findings that intricate, but
      nonthreatening repeating patterns can have similar attention-grabbing properties
      to animal skin patterns have important implications for the fashion industry and
      wildlife trade.

PMID- 29455570
TI  - Unmet digital health service needs in dermatology patients.
AB  - BACKGROUND: Digital health services are rapidly gaining acceptance in healthcare
      systems. Dermatology as an image-centric specialty is particularly well suited
      for telemedical services. However, dermatology patients' demands of electronic
      services remain largely unexplored. METHODS: This study investigated patients'
      views in primary, secondary, and tertiary referral centers. In August 2017, 841
      questionnaires were filled in by dermatology patients. RESULTS: 76.34% expressed
      interest in using digital healthcare services as part of medical consultations.
      84.41% of all patients would complete their initial registration form
      electronically. Fewer patients were comfortable with sending pictures of skin
      changes to their doctors using email (40.89%) or mobile health applications
      (40.61%). Specific interest was indicated for arranging appointments online
      (90.80%) and electronically-placed prescriptions (76.56%), rather than online
      learning videos (42.03%), and actual online consultations (34.53%). 65.37% of
      patients would pay for online consultations themselves. CONCLUSIONS: Taken
      together, interest in electronic health services is high in dermatology patients.
      Our data suggest that readily understandable electronic services such as online
      arranged appointments and electronic prescriptions are of higher interest to
      patients than the current type of online consultations. Therefore, the full
      potential of teledermatology still remains to be tapped by newer, more attractive
      forms of services closely adapted to patients' demands.

PMID- 29455571
TI  - Genetic Variation of the Kinases That Phosphorylate Tenofovir and Emtricitabine
      in Peripheral Blood Mononuclear Cells.
AB  - Tenofovir (TFV) disoproxil fumarate and emtricitabine (FTC) are used in
      combination for HIV treatment and pre-exposure prophylaxis (PrEP). TFV disoproxil
      fumarate is a prodrug that undergoes diester hydrolysis to TFV. FTC and TFV are
      nucleoside/nucleotide reverse transcriptase inhibitors that upon phosphorylation
      to nucleotide triphosphate analogs competitively inhibit HIV reverse
      transcriptase. We previously demonstrated that adenylate kinase 2, pyruvate
      kinase, muscle and pyruvate kinase, liver and red blood cell phosphorylate TFV in
      peripheral blood mononuclear cells (PBMC). To identify the kinases that
      phosphorylate FTC in PBMC, siRNAs targeted toward kinases that phosphorylate
      compounds structurally similar to FTC were delivered to PBMC, followed by
      incubation with FTC and the application of a matrix-assisted laser desorption
      ionization-mass spectrometry method and ultra high performance liquid
      chromatography-UV to detect the formation of FTC phosphates. Knockdown of
      deoxycytidine kinase decreased the formation of FTC-monophosphate, while siRNA
      targeted toward thymidine kinase 1 decreased the abundance of FTC-diphosphate.
      Knockdown of either cytidine monophosphate kinase 1 or phosphoglycerate kinase 1
      decreased the abundance of FTC-triphosphate. Next-generation sequencing of
      genomic DNA isolated from 498 HIV-uninfected participants in the HIV Prevention
      Trials Network 069/AIDS Clinical Trials Group A5305 clinical study, revealed 17
      previously unreported genetic variants of TFV or FTC phosphorylating kinases. Of
      note, four individuals were identified as simultaneous carriers of variants of
      both TFV and FTC activating kinases. These results identify the specific kinases
      that activate FTC in PBMC, while also providing further insight into the
      potential for genetic variation to impact TFV and FTC activation.

PMID- 29455572
TI  - Safer conception among HIV-1 serodiscordant couples in East Africa: understanding
      knowledge, attitudes, and experiences.
AB  - For HIV-1 serodiscordant couples, HIV-1 exposure and risk of transmission is
      heightened during pregnancy attempts, but safer conception strategies can reduce
      risk. As safer conception programs are scaled up, understanding couples'
      preferences and experiences can be useful for programmatic recommendations. We
      followed 1013 high-risk, heterosexual HIV-1 serodiscordant couples from Kenya and
      Uganda for two years in an open-label delivery study of integrated pre-exposure
      prophylaxis (PrEP) and antiretroviral therapy (ART), the Partners Demonstration
      Project. We used descriptive statistics to describe the cohort and multivariate
      logistic regression to characterize women who reported use of a safer conception
      strategy by their first annual visit. 66% (569/859) of women in the study were
      HIV-infected and 73% (627/859) desired children in the future. At the first
      annual visit, 59% of women recognized PrEP, 58% ART, 50% timed condomless sex,
      23% self-insemination, and fewer than 10% recognized male circumcision, STI
      treatment, artificial insemination, and sperm washing as safer conception
      strategies. Among those recognizing these strategies and desiring pregnancy, 37%
      reported using PrEP, 14% ART, and 30% timed condomless sex. Women who reported
      discussing their fertility desires with their male partners were more likely to
      report having used at least one strategy for safer conception (adjusted odds
      ratio = 1.91, 95% confidence interval:1.26-2.89). Recognition of use of safer
      conception strategies among women who expressed fertility desires was low, with
      ARV-based strategies and self-insemination the more commonly recognized and used
      strategies. Programs supporting HIV-1 serodiscordant couples can provide
      opportunities for couples to talk about their fertility desires and foster
      communication around safer conception practices.

PMID- 29455573
TI  - A CREB-mediated increase in miRNA let-7f during prolonged beta-agonist exposure:
      a novel mechanism of beta2-adrenergic receptor down-regulation in airway smooth
      muscle.
AB  - beta2-Adrenergic receptors (beta2ARs) desensitize during continuous agonist
      activation, which manifests clinically as tachyphylaxis. beta-Agonist
      desensitization of beta2ARs in human airway smooth muscle (HASM) cells is
      recognized in the treatment of asthma and may be related to poor outcomes. Rapid
      events in desensitization include receptor phosphorylation and internalization,
      but mechanisms responsible for the decrease in receptor protein after prolonged
      agonist exposure (down-regulation) are ill defined. The microRNA (miRNA) let-7f
      regulates beta2AR expression by translational repression. In cultured HASM cells
      from nonasthmatic and asthmatic lungs, 18 h of beta-agonist exposure increased
      let-7f by 2-3-fold, concomitant with a ~90% decrease in beta2ARs. Inhibition of
      let-7f attenuated this down-regulation response by ~50%. The let-7f increase was
      found to be cAMP/PKA-dependent. The mechanism of the let-7f increase was found by
      chromatin immunoprecipitation to be from activated cAMP response element-binding
      protein (CREB) binding to the let-7f promoter, thereby increasing let-7f
      expression. Knockdown of CREB attenuated agonist-promoted beta2AR down-regulation
      by ~50%. Thus, beta2AR down-regulation occurs as a result of not only
      internalized receptor degradation but also a novel cAMP/PKA/CREB-mediated
      increase in let-7f, which causes enhanced repression of the beta2AR gene,
      adrenoreceptor beta2 ( ADRB2) translation and represents ~50% of the net loss of
      receptors observed after prolonged agonist exposure. This mechanism is apparent
      in asthmatic HASM cells, indicating relevance in a disease model.-Kim, D., Cho,
      S., Woo, J. A., Liggett, S. B. A CREB-mediated increase in miRNA let-7f during
      prolonged beta-agonist exposure: a novel mechanism of beta2-adrenergic receptor
      down-regulation in airway smooth muscle.

PMID- 29455575
TI  - Exercise counteracts the homeostatic decrease in thermogenesis caused by caloric
      restriction in sheep.
AB  - Caloric restriction causes a homeostatic reduction in thermogenesis. We aimed to
      determine whether exercise could counteract this. We studied four groups of
      normal-weight ewes ( n = 5), including control sedentary fed ad libitum, exercise
      fed ad libitum (30 min/d, 5 d/wk), diet-restricted (70% of ad libitum food
      intake), and combined diet and exercise. Temperature probes implanted in sternal
      and retroperitoneal adipose tissue and skeletal muscle measured thermogenesis.
      After the 4-wk intervention, hypothalami were collected for in situ
      hybridization, and fat and muscle biopsies were collected for real-time PCR and
      Western blotting. Combined diet and exercise reduced adiposity ( P < 0.05).
      Caloric restriction alone reduced overnight temperatures in sternal and
      retroperitoneal fat ( P < 0.05), which was counteracted by exercise ( P < 0.05).
      Exercise did not induce expression of cellular markers of browning in adipose
      tissue. There was no effect of diet or exercise on skeletal muscle thermogenesis.
      Combined diet and exercise increased the expression of neuropeptide Y and agouti
      related protein in the hypothalamic arcuate nucleus ( P < 0.05), consistent with
      reduced adiposity. Gene expressions of key hypothalamic appetite-regulating
      peptides were not associated with altered thermogenesis. We demonstrate that
      exercise counteracts the inhibitory effect of caloric restriction to restore
      thermogenesis in adipose tissue of sheep.-Fuller-Jackson, J.-P., Clarke, I. J.,
      Rao, A., Henry, B. A. Exercise counteracts the homeostatic decrease in
      thermogenesis caused by caloric restriction in sheep.

PMID- 29455574
TI  - Immune responsive resolvin D1 programs myocardial infarction-induced cardiorenal
      syndrome in heart failure.
AB  - Resolvins are innate, immune responsive, bioactive mediators generated after
      myocardial infarction (MI) to resolve inflammation. The MI-induced bidirectional
      interaction between progressive left ventricle (LV) remodeling and kidney
      dysfunction is known to advance cardiorenal syndrome (CRS). Whether resolvins
      limit MI-induced cardiorenal inflammation is unclear. Thus, to define the role of
      exogenous resolvin D (RvD)-1 in post-MI CRS, we subjected 8- to 12-wk-old male
      C57BL/6 mice to coronary artery ligation. RvD1 was injected 3 h after MI. MI mice
      with no treatment served as MI controls (d 1 and 5). Mice with no surgery served
      as naive controls. In the injected mice, RvD1 promoted neutrophil (CD11b+/Ly6G+)
      egress from the infarcted LV, compared with the MI control group at d 5,
      indicative of neutrophil clearance and thereby resolved inflammation. Further,
      RvD1-injected mice showed higher reparative macrophages (F4/80+/Ly6Clow/CD206+)
      in the infarcted LV than did MI control mice at d 5 after MI. RvD1 suppressed the
      miRNA storm at d 1 and limited the MI-induced edematous milieu in a remote area
      of the LV compared with the MI control at d 5 after MI. Also, RvD1 preserved the
      nephrin expression that was diffuse in the glomerular membrane at d 5 and 28 in
      MI controls, indicating renal injury. RvD1 attenuated MI-induced renal
      inflammation, decreasing neutrophil gelatinase-associated lipocalin and
      proinflammatory cytokines and chemokines in the kidney compared with the MI
      control. In summary, RvD1 clears MI-induced inflammation by increasing resolving
      leukocytes and facilitates renoprotective mechanisms to limit CRS in acute and
      chronic heart failure.-Halade, G. V., Kain, V., Serhan, C. N. Immune responsive
      resolvin D1 programs myocardial infarction-induced cardiorenal syndrome in heart
      failure.

PMID- 29455578
TI  - Evaluating the effects of copper supplement during pregnancy on premature rupture
      of membranes and pregnancy outcome: some statistical issues.

PMID- 29455576
TI  - Central Infusion of Insulin-Like Growth Factor-1 Increases Hippocampal
      Neurogenesis and Improves Neurobehavioral Function after Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) produces neuronal dysfunction and cellular loss that
      can culminate in lasting impairments in cognitive and motor abilities.
      Therapeutic agents that promote repair and replenish neurons post-TBI hold
      promise in improving recovery of function. Insulin-like growth factor-1 (IGF-1)
      is a neurotrophic factor capable of mediating neuroprotective and neuroplasticity
      mechanisms. Targeted overexpression of IGF-1 enhances the generation of
      hippocampal newborn neurons in brain-injured mice; however, the translational
      neurogenic potential of exogenously administered IGF-1 post-TBI remains unknown.
      In a mouse model of controlled cortical impact, continuous
      intracerebroventricular infusion of recombinant human IGF-1 (hIGF) for 7 days,
      beginning 15 min post-injury, resulted in a dose-dependent increase in the number
      of immature neurons in the hippocampus. Infusion of 10 MUg/day of IGF-1 produced
      detectable levels of hIGF-1 in the cortex and hippocampus and a concomitant
      increase in protein kinase B activation in the hippocampus. Both motor function
      and cognition were improved over 7 days post-injury in IGF-1-treated cohorts.
      Vehicle-treated brain-injured mice showed reduced hippocampal immature neuron
      density relative to sham controls at 7 days post-injury. In contrast, the density
      of hippocampal immature neurons in brain-injured mice receiving acute onset IGF-1
      infusion was significantly higher than in injured mice receiving vehicle and
      equivalent to that in sham-injured control mice. Importantly, the neurogenic
      effect of IGF-1 was maintained with as much as a 6-h delay in the initiation of
      infusion. These data suggest that central infusion of IGF-1 enhances the
      generation of immature neurons in the hippocampus, with a therapeutic window of
      at least 6 h post-injury, and promotes neurobehavioral recovery post-TBI.

PMID- 29455579
TI  - VMAT2 Inhibitors for Tardive Dyskinesia-Practice Implications.
AB  - Tardive dyskinesia is a potentially irreversible, debilitating, hyperkinetic
      movement disorder that can result from dopamine receptor antagonists. Prompt
      recognition and resolution of symptoms are instrumental in preventing disease
      irreversibility, though current treatment options have fallen short of robust,
      effective, and long-term symptom control. In April 2017, the Food and Drug
      Administration (FDA) approved 2 new vesicular monoamine transporter 2 (VMAT2)
      inhibitors, deutetrabenazine and valbenazine, for chorea related to Huntington's
      disease and tardive dyskinesia, respectively. These agents were pharmacologically
      modified from tetrabenazine, a VMAT2 inhibitor used off-label in the treatment of
      tardive dyskinesia. Despite FDA-labeled indications of deutetrabenazine and
      valbenazine, each agent was explored as a treatment option for those with tardive
      dyskinesia. In this study, the pharmacologic modifications of the 2 new VMAT2
      inhibitors are described, with detailed explanation as to how these may impact
      clinical practice. The associated case series, observational studies, and
      clinical trials exploring their use in the treatment of tardive dyskinesia are
      reported with expert opinion on practice implication.

PMID- 29455577
TI  - Exploring autophagy with Gene Ontology.
AB  - Autophagy is a fundamental cellular process that is well conserved among
      eukaryotes. It is one of the strategies that cells use to catabolize substances
      in a controlled way. Autophagy is used for recycling cellular components,
      responding to cellular stresses and ridding cells of foreign material.
      Perturbations in autophagy have been implicated in a number of pathological
      conditions such as neurodegeneration, cardiac disease and cancer. The growing
      knowledge about autophagic mechanisms needs to be collected in a computable and
      shareable format to allow its use in data representation and interpretation. The
      Gene Ontology (GO) is a freely available resource that describes how and where
      gene products function in biological systems. It consists of 3 interrelated
      structured vocabularies that outline what gene products do at the biochemical
      level, where they act in a cell and the overall biological objectives to which
      their actions contribute. It also consists of 'annotations' that associate gene
      products with the terms. Here we describe how we represent autophagy in GO, how
      we create and define terms relevant to autophagy researchers and how we
      interrelate those terms to generate a coherent view of the process, therefore
      allowing an interoperable description of its biological aspects. We also describe
      how annotation of gene products with GO terms improves data analysis and
      interpretation, hence bringing a significant benefit to this field of study.

PMID- 29455580
TI  - From Family Involvement to Family Inclusion in Nursing Home Settings: A Critical
      Interpretive Synthesis.
AB  - The provision of care work by families plays an integral role in the quality of
      life of older adults living in a nursing home setting. This critical interpretive
      synthesis examines family members' perceptions of their roles and
      responsibilities in nursing home settings and interrogates the structural and
      relational barriers and enablers to family involvement as they relate to
      fostering an inclusive environment. Electronic databases and published literature
      were searched for empirical studies that were conducted in a nursing home setting
      and described involvement from the perspective of family members. Thirty-two
      articles published between 2006 and 2016 were included in the review. Although
      involvement comprised a variety of roles and responsibilities, it was grounded in
      family-resident relationships, influenced by family-staff relationships, and
      deeply affected by broader sociopolitical factors. We conclude that involvement
      should be understood as a democratic process with supporting policies and
      programs to encourage family inclusion in facility life.

PMID- 29455581
TI  - Keeping it tight: The relationship between bacterial dysbiosis, septate
      junctions, and the intestinal barrier in Drosophila.
AB  - Maladaptive changes in the intestinal flora, typically referred to as bacterial
      dysbiosis, have been linked to intestinal aging phenotypes, including an increase
      in intestinal stem cell (ISC) proliferation, activation of inflammatory pathways,
      and increased intestinal permeability1,2. However, the causal relationships
      between these phenotypes are only beginning to be unravelled. We recently
      characterized the age-related changes that occur to septate junctions (SJ)
      between adjacent, absorptive enterocytes (EC) in the fly intestine. Changes could
      be observed in the overall level of SJ proteins, as well as the localization of a
      subset of SJ proteins. Such age-related changes were particularly noticeable at
      tricellular junctions (TCJ)3. Acute loss of the Drosophila TCJ protein Gliotactin
      (Gli) in ECs led to rapid activation of stress signalling in stem cells and an
      increase in ISC proliferation, even under axenic conditions; a gradual disruption
      of the intestinal barrier was also observed. The uncoupling of changes in
      bacteria from alterations in ISC behaviour and loss of barrier integrity has
      allowed us to begin to explore the interrelationship of these intestinal aging
      phenotypes in more detail and has shed light on the importance of the proteins
      that contribute to maintenance of the intestinal barrier.

PMID- 29455583
TI  - Author Correction.

PMID- 29455582
TI  - Non-visualization of fetal gallbladder in microarray era - a retrospective cohort
      study and review of the literature.
AB  - OBJECTIVE: The objective of this study is to examine the frequency of abnormal
      Chromosomal Microarray (CMA) analyses among fetuses with isolated non
      visualization of fetal gallbladder. METHODS: Data from CMA analyses performed due
      to isolated non-visualization of fetal gallbladder between January 2013 and
      September 2016 were retrospectively acquired from a computerized database of the
      Israeli Ministry of Health. The results were compared with the rate for
      clinically significant CMA findings in general population, based on a large
      cohort of 5541 pregnancies undergoing CMA due to maternal request, and a
      systematic review of 9272 cases with normal ultrasound. RESULTS: Of 45
      pregnancies with isolated non-visualization of fetal gallbladder, CMA testing
      yielded one (2.22%) gain-of-copy-number variant at 16p11.2, categorized as
      "pathogenic". In addition, one finding of unknown significance was demonstrated.
      The risk for clinically meaningful CMA findings among pregnancies with isolated
      absent gallbladder was not significantly increased compared to control
      population. CONCLUSIONS: To the best of our knowledge, this study is the first
      report describing the rate of pathogenic CMA results in fetuses with isolated non
      visualization of fetal gallbladder. The results, in conjunction with previous
      studies, show that the risk for abnormal CMA results in pregnancies diagnosed
      with non-visualized gallbladder is not significantly different from pregnancies
      with normal ultrasound.

PMID- 29455586
TI  - Supportive Care Services Address Many Patient Needs.

PMID- 29455585
TI  - Making the Move to a Multispecialty Oncology Practice.

PMID- 29455584
TI  - HEPES activates a MiT/TFE-dependent lysosomal-autophagic gene network in cultured
      cells: A call for caution.
AB  - In recent years, the lysosome has emerged as a highly dynamic, transcriptionally
      regulated organelle that is integral to nutrient-sensing and metabolic rewiring.
      This is coordinated by a lysosome-to-nucleus signaling nexus in which MTORC1
      controls the subcellular distribution of the microphthalmia-transcription factor
      E (MiT/TFE) family of "master lysosomal regulators". Yet, despite the importance
      of the lysosome in cellular metabolism, the impact of traditional in vitro
      culture media on lysosomal dynamics and/or MiT/TFE localization has not been
      fully appreciated. Here, we identify HEPES, a chemical buffering agent that is
      broadly applied in cell culture, as a potent inducer of lysosome biogenesis.
      Supplementation of HEPES to cell growth media is sufficient to decouple the
      MiT/TFE family members-TFEB, TFE3 and MITF-from regulatory mechanisms that
      control their cytosolic retention. Increased MiT/TFE nuclear import in turn
      drives the expression of a global network of lysosomal-autophagic and innate host
      immune response genes, altering lysosomal dynamics, proteolytic capacity,
      autophagic flux, and inflammatory signaling. In addition, siRNA-mediated MiT/TFE
      knockdown effectively blunted HEPES-induced lysosome biogenesis and gene
      expression profiles. Mechanistically, we show that MiT/TFE activation in response
      to HEPES requires its macropinocytic ingestion and aberrant lysosomal storage/pH,
      but is independent of MTORC1 signaling. Altogether, our data underscore the
      cautionary use of chemical buffering agents in cell culture media due to their
      potentially confounding effects on experimental results.

PMID- 29455587
TI  - Practice Efficiency and Practice Quality: Flip Sides of the Same Coin.

PMID- 29455588
TI  - Cancer Care Is Costly.

PMID- 29455589
TI  - Genetic Testing for Cancer: Legal, Ethical, and Practical Issues for the
      Practicing Oncologist.

PMID- 29455590
TI  - The CMS Physician Quality Reporting Initiative.

PMID- 29455591
TI  - C3: Colorectal Cancer Coalition - Pushing for Better Research, Faster.

PMID- 29455592
TI  - What's New at PLWC.org.

PMID- 29455593
TI  - Acute compressive stress activates RHO/ROCK-mediated cellular processes.
AB  - The ability to rapidly respond to applied force underpins cell/tissue
      homeostasis. This response is mediated by mechanotransduction pathways that
      regulate remodeling and tension of the actomyosin cytoskeleton to counterbalance
      external forces. Enhanced extracellular matrix tension hyper-activates
      mechanotransduction and characterizes diseased states such as cancer, but is also
      required for normal epidermal regeneration. While the impact of extracellular
      matrix tension on signaling and cell biology are well appreciated, that of acute
      compressive force is under-studied. We show here that acute compressive force
      applied to cells and tissues in a native 3-dimensional context elevates RHOA-GTP
      levels and increases regulatory myosin phosphorylation, actomyosin contractility
      and tension via ROCK. In consequence, cell proliferation was increased, as was
      the expression of regulators of epithelial-mesenchymal transition.
      Pharmacological inhibition of ROCK abrogated myosin phosphorylation, but not RHOA
      activation. Our results strongly suggest that acute compressive stress impairs
      cellular homeostasis in a RHO/ROCK-dependent manner, with implications for
      disease states such as cancer.

PMID- 29455594
TI  - Vaginal birth after a cesarean delivery for arrest of descent.
AB  - OBJECTIVE: The objective of this study is to determine vaginal birth after
      cesarean (VBAC) success rates for patients with a prior cesarean delivery (CD)
      for arrest of descent, as well as determine any predictors for success. STUDY
      DESIGN: This was a retrospective cohort study of all patients delivered by a
      single MFM practice from 2005 to 2017 with a singleton pregnancy and one prior CD
      for arrest of descent. We estimated the rate and associated risk factors for
      successful VBAC. RESULTS: We included 208 patients with one prior CD for arrest
      of descent, 100 (48.1%) of whom attempted a trial of labor after cesarean (TOLAC)
      with a VBAC success rate was 84/100 (84%, 95% CI 76-90%). Among the women who
      attempted TOLAC, women with a prior vaginal delivery >24 weeks' had a
      significantly higher VBAC success rate (91.8% versus 71.8%, p = .01). Maternal
      age, body mass index, estimated fetal weight, induction of labor, and cervical
      dilation were not associated with a higher VBAC success rate. CONCLUSIONS: For
      women with a prior CD for arrest of descent, VBAC success rates are high. This
      suggests that arrest of descent is mostly dependent on factors unique to each
      pregnancy and not due to an inadequate pelvis or recurring conditions. Women with
      a prior CD for arrest of descent should not be discouraged from attempting TOLAC
      in a subsequent pregnancy due to concerns about the likelihood of success.

PMID- 29455596
TI  - 2007 Update of ASCO Practice Guideline for the Initial Hormonal Management of
      Androgen-Sensitive Metastatic, Recurrent, or Progressive Prostate Cancer:
      Guideline Summary.

PMID- 29455595
TI  - Talking With Patients About the Cost of Cancer Care.

PMID- 29455597
TI  - Advocacy Through the Medicare Process.

PMID- 29455598
TI  - Hospital and Private Practice Partnerships: Which Model Is Right for You?

PMID- 29455599
TI  - eHealth Initiative: Improving Health Care Through Information Technology.

PMID- 29455600
TI  - Professional Advisors: They're Worth It.

PMID- 29455601
TI  - Practical Tips for the Oncology Practice.

PMID- 29455602
TI  - Making the Sum Greater Than Its Parts: Nurse Practitioners and Physicians.

PMID- 29455603
TI  - Marketing Your State Society.

PMID- 29455604
TI  - The Difficult Patient.

PMID- 29455605
TI  - Editorial: Physician-Hospital Partnership-What Really Counts?

PMID- 29455606
TI  - Research Advocacy Network: Advancing Patient-Focused Research.

PMID- 29455607
TI  - Updated Patient Guide on Hormone Therapy for Advanced Prostate Cancer.

PMID- 29455608
TI  - Maintenance of Certification: My Perspective.

PMID- 29455609
TI  - Selecting an Electronic Health Record System.

PMID- 29455610
TI  - Using Skype to support remote clinical supervision for health professionals
      delivering a sustained maternal early childhood programme: a phenomenographical
      study.
AB  - BACKGROUND: Skype technology was implemented by the Australian Maternal Early
      Childhood Sustained Home-visiting (MECSH) Support Service as a tool for the
      remote provision of clinical supervision for clinicians working in the MECSH
      program in Seoul, South Korea. OBJECTIVES: To gain a better understanding of the
      processes underpinning sustainable delivery of remote clinical supervision using
      digital technologies. DESIGN: A phenomenographical study. METHODS: Recorded notes
      and reflections on each supervision session, noting exemplars and characteristics
      of the experience were read and re-read to derive the characterizations of the
      experience. RESULTS: The experience has provided learnings in three domains: (1)
      the processes in using Skype; (2) supervisory processes; and (3) language
      translation, including managing clarity of, and time for translation. CONCLUSION:
      Skype has potential for use in remote provision of clinical supervision,
      including where translation is required. Further research evaluating the benefit
      of telesupervision from supervisor and supervisee perspectives is necessary to
      determine if it is a sustainable process.

PMID- 29455611
TI  - Evaluation of foetal neurological behaviour in hypothyroid pregnant females - a
      pilot study.
AB  - OBJECTIVES: Maternal hypothyroidism is known for its possible deleterious effect
      on the neurocognitive function of the offspring. The aim of the current study is
      to investigate if maternal hypothyroidism also affects foetal neurological
      behaviour. METHODS: Fifty foetuses were examined for abnormal neurological
      behaviour from 25 euthyroid and 25 hypothyroid age matched pregnant females,
      between 28 and 38 weeks gestation. The hypothyroid group was further subdivided
      into controlled (n = 5) and uncontrolled (n = 20) groups. Evaluation of foetal
      neurological behaviour using Kurjak's antenatal neurodevelopmental test (KANET)
      test was performed. RESULTS: Mean total KANET score was significantly lower for
      foetuses in the hypothyroid group compared to the euthyroid (p < .001, 95% CI: 2
      6). The number of foetuses showing pathological scores was significantly higher
      in the hypothyroid group (9, 36%) compared to euthyroid (1, 4%) (p < .005). The
      distribution of total KANET score was significantly different between the two
      groups (p = .017). Foetuses in the uncontrolled hypothyroid group showed lower
      mean KANET scores (9.650 +/- 2.907 versus 10.80 +/- 3.03) and higher frequency of
      pathological scores compared to controlled (8 = 40% versus 1 = 20%) although
      without statistical significance. The distribution of total KANET score was not
      statistically significant between the two groups (p = .893). CONCLUSIONS: Overt
      maternal hypothyroidism may adversely affect foetal neurological behaviour.
      Correlation of prenatal findings with postnatal long-term neurological
      development is recommended in such cases.

PMID- 29455612
TI  - Are levels of coping with stress in pregnancy with gestational diabetes worse
      than in healthy pregnancy?
AB  - PURPOSE: The purpose of this study was to analyze the levels of coping with
      stress in healthy pregnant women in comparison with the levels of coping with
      stress in pregnant women with gestational diabetes mellitus (GDM). MATERIALS AND
      METHODS: In the study, the descriptive cross-sectional research design was used.
      The study was carried out with 218 pregnant women in total. RESULTS: It was found
      that the healthy pregnant women had a higher total score for coping with stress
      and used the self-confident coping style, one of the effective coping styles,
      more frequently when compared to the pregnant women with GDM (p < .001). In
      addition, the pregnant women with GDM used the desperate coping style, one of the
      ineffective coping styles, more frequently than the healthy pregnant women (p <
      .001). CONCLUSIONS: Diabetes education that nurses give should allow not only the
      nurses to evaluate the coping levels of pregnant women with GDM, but also to
      teach these pregnant women how to use effective coping styles.

PMID- 29455613
TI  - Liposuction-assisted circumferential trimming in treatment of axillary osmidrosis
      (AO).
AB  - BACKGROUND: The study is to investigate the effectiveness and safety of the
      minimally invasive treatment for axillary osmidrosis by liposuction assisted
      circumferential trimming. METHODS: It was a retrospective study. From July 2014
      to July 2017, 79 patients underwent superficial liposuction and circumferential
      trimming for bilateral axillary osmidrosis. The preoperative and postoperative
      degree of axillary malodor was measured by doctors and the patients themselves.
      In the doctor's evaluation, the odor levels were scored by the sniffing method
      before and 1 year after treatment. In the patient's self-assessment, each patient
      selected a scale value to convey his/her satisfaction during the visits after 1
      year. The complications were recorded. RESULTS: The follow-up period ranged from
      12 to 24 months after surgery, and the mean follow-up period was 16 months. 75
      (94.9%) had good results, four (5.1%) had moderate malodor or recurrence after
      one year. When considering patient's own satisfaction, 93.7% (74/79) of patients
      were satisfied with the outcomes after one year. The partial epidermis necrosis
      was observed in four patients, it healed spontaneously without scarring. Three
      patients had a small amount of hematoma which was easily evacuated through the
      central primary incision. There was no other serious side effect. CONCLUSIONS:
      The liposuction assisted circumferential trimming technique is proved reliable
      and safe in treatment for axillary osmidrosis.

PMID- 29455614
TI  - DDR1: A major player in renal diseases.
AB  - Discoidin Domain Receptor 1 (DDR1) belongs to a family of two non-integrin
      collagen receptors, DDR1 and DDR2, which display a tyrosine kinase activity. DDR1
      has been widely studied in different kind of pathologies including chronic kidney
      diseases (CKD). The aims of this commentary are 1. to review the existing
      information about DDR1 expression in healthy and diseased kidney, 2. to comment
      the data highlighting DDR1 as a major actor in CKD, 3. to suggest areas of
      research which require further investigation to better characterize the signaling
      pathways regulating DDR1 role in CKD. The results recapitulated in this
      commentary emphasize the involvement of DDR1 in the pro-inflammatory and pro
      fibrotic processes which drives the development of CKD. They also underline the
      beneficial effect of its blockade in pre-clinical models and thus, reinforce its
      status of interesting therapeutic target.

PMID- 29455615
TI  - Do Systems or Doctors Support Higher Value Care?

PMID- 29455616
TI  - Is the fetal cerebroplacental ratio better that the estimated fetal weight in
      predicting adverse perinatal outcomes in a low risk cohort?
AB  - OBJECTIVE: In high-risk pregnancies combining the cerebro-placental ratio (CPR)
      with the estimated fetal weight (EFW) improves the identification of vulnerable
      fetuses. The purpose of this study was to assess the CPR and EFW's ability to
      predict adverse obstetric and perinatal outcomes in a low-risk pregnancy, when
      measured late in gestation. METHODS: This was a retrospective study of women who
      birthed at Mater Mothers Hospitals, Brisbane, Australia between 2010 and 2015. We
      included all nonanomalous singleton pregnancies that had an ultrasound scan
      performed between 36 and 38 weeks gestation. Excluded was any major congenital
      abnormality, aneuploidy, multiple pregnancy, preterm birth, maternal
      hypertension, or diabetes. The primary outcome was a severe composite neonatal
      outcome (SCNO) defined as severe acidosis (umbilical cord artery pH <7.0, cord
      lactate >=6 mmol/L, cord base excess <=-12 mmol/L) Apgar score <=3 at 5 minutes,
      admission to the neonatal intensive care unit (NICU), and death. A low CPR was
      defined as <10th centile for gestation and small for gestational age (SGA) was
      defined as an EFW <10th centile and appropriate for gestational age (AGA) was
      defined as EFW >=10th centile. RESULTS: Of 2425 pregnancies, 13.2% (321/2425) had
      a fetus with a CPR <10th centile and 13.7% (332/2425) with an EFW <10th centile.
      Both a low CPR and SGA predicted the SCNO. Individually a low CPR and SGA had
      sensitivity for detection of SCNO of 23.3% and 24.7%, respectively which
      increased to 36.7% when combined. Both were associated with emergency caesarean
      for nonreassuring fetal status (NRFS), as well as early-term birth and admission
      to NICU. Stratifying the population into EFW <10th centile and EFW >=10th
      centile, a low CPR maintained its association with the SCNO, early-term birth and
      emergency caesarean for NRFS in the cohort with an EFW <10th centile but SCNO
      lost its association with a low CPR in the EFW >10th cohort. Stratifying the
      population into CPR <10th centile and CPR >10th centile, a low EFW was associated
      with early-term birth, induction of labor, admission to NICU, and the SCNO.
      CONCLUSIONS: In a low-risk cohort both the CPR and EFW individually and in
      combination predicts adverse obstetric and perinatal outcomes when measured late
      in pregnancy. However, the predictive value was enhanced when both were used in
      combination.

PMID- 29455617
TI  - The role of premorbid adjustment in schizophrenia: Focus on cognitive remediation
      outcome.
AB  - Premorbid adjustment has been associated with several outcomes in schizophrenia
      and has been proposed as an index of cognitive reserve. This study aims to
      comprehensively analyse the relation between premorbid adjustment and clinical,
      neurocognitive, socio-cognitive and functional assessments, as well as to
      investigate the effect of premorbid adjustment on cognitive improvements after a
      cognitive remediation therapy protocol. Seventy-nine clinically stabilised
      outpatients with schizophrenia underwent a combined intervention consisting of
      cognitive remediation therapy added to standard rehabilitation therapy. All
      patients were assessed at baseline for psychopathology, premorbid adjustment,
      intellectual level, cognition and functioning. Cognitive evaluations were also
      repeated after the intervention. At baseline, significant correlations were
      observed between premorbid adjustment and working memory. The global cognitive
      improvement after treatment was significantly predicted by age and premorbid
      adjustment. This study confirms the association between premorbid adjustment and
      cognitive impairment and is the first to highlight the possible role of premorbid
      adjustment on the capacity to recover from cognitive deficits through a cognitive
      remediation therapy protocol. The data suggest that cognitive remediation may be
      particularly effective for people in the early course and that the assessment of
      premorbid adjustment could be of value to design individualised interventions.

PMID- 29455618
TI  - Maternal protein S activity is associated with massive hemorrhage during
      caesarean section: retrospective case-control study.
AB  - OBJECTIVE: The objective of this study is to identify any correlation between the
      maternal protein S (PS) activity, which decreases spontaneously during normal
      pregnancy, and the pregnancy outcome, especially the amount of bleeding during
      caesarean section (CS). MATERIALS AND METHODS: We analyzed 129 pregnant women who
      received elective CS at our hospital which is a tertiary perinatal center. The
      relationship between the amount of intraoperative hemorrhage and PS activity was
      estimated by simple linear regression. Univariate and multivariate analyses were
      also performed to determine whether or not the maternal PS activity was
      associated with massive hemorrhage (>1000 g). RESULTS: The maternal PS activity
      correlated with the amount of intraoperative hemorrhage (p = .048, r = 0.175) and
      could be an independent predictor of massive hemorrhage (odds ratio 1.06; 95%
      confidence interval 1.01-1.12; p = .013). CONCLUSIONS: Maternal PS activity was
      associated with the amount of hemorrhage during CS and the occurrence of massive
      hemorrhage. PS activity reduction naturally occurring during pregnancy could
      contribute to alleviation of massive hemorrhage.

PMID- 29455619
TI  - Shaping Cell Fate: Influence of Topographical Substratum Properties on Embryonic
      Stem Cells.
AB  - Development of multicellular organisms is a highly orchestrated process, with
      cells responding to factors and features present in the extracellular milieu.
      Changes in the surrounding environment help decide the fate of cells at various
      stages of development. This review highlights recent research that details the
      effects of mechanical properties of the surrounding environment and extracellular
      matrix and the underlying molecular mechanisms that regulate the behavior of
      embryonic stem cells (ESCs). In this study, we review the role of mechanical
      properties during embryogenesis and discuss the effect of engineered
      microtopographies on ESC pluripotency.

PMID- 29455620
TI  - Bacterial-mediated biodegradation of pentachlorophenol via electron shuttling.
AB  - Pentachlorophenol (PCP) degradation by soil indigenous bacteria represents a
      practical and cost-effective solution. In the present study, bacteria isolated
      from paddy soil was investigated and the role of electron shuttling (ES) in the
      PCP degradation process was assessed. Two strains demonstrated the highest PCP
      degradation of 93.5% and 94.88% in the presence of citrate and were identified
      using 16S rRNA phylogenetic analysis as Pseudomonas chengduensis and Pseudomonas
      plecoglossicida, respectively. Both strains showed higher PCP degradation in free
      form as opposed to a reduced activity in immobilized and respiratory impaired
      form. The addition of pyruvate resulted in about 80% PCP degradation in 5 days
      for P. chengduensis, on the other hand, P. plecoglossicida showed the same result
      under anaerobic conditions whether pyruvate was added or not. Phenazine and the
      outer membrane c-type cytochrome were reported only for P. chengduensis as
      opposed to P. plecoglossicida. The results indicate that despite following
      different approaches in PCP degradation, both strains are useful in PCP clean-up
      under aerobic and anaerobic conditions and in free direct contact. The
      degradation is enhanced via ES. This is considered both an effective and feasible
      technology for in situ clean-up of contaminated sites or on-site bioreactors.

PMID- 29455621
TI  - Optimization of Endometrial Decidualization in the Menstruating Mouse Model for
      Preclinical Endometriosis Research.
AB  - BACKGROUND: To induce endometrial decidualization in rodents, an intrauterine oil
      stimulus can be delivered via the nontraumatic vagina or via the traumatic
      laparotomy. However, there is considerable variation in amount of decidualization
      using these inducing methods. Therefore, we studied which oil delivery route
      could achieve the highest rate of endometrial decidualization along the full
      length of both uterine horns. METHODS: To induce decidualization, ovariectomized
      C57Bl/6J mice were injected with estrogen (100 ng/day; 3 days). A progesterone
      pellet (5 mg) was implanted subcutaneously, followed by estrogen injections (5
      ng/day; 3 days). Oil (20 uL/horn) was injected in the uterus via laparotomy,
      laparoscopy, or vagina. Four days later, the pellet was removed, followed by
      hysterectomy after 4 to 6 hours. Endometrial decidualization was evaluated
      macroscopically and microscopically using hematoxylin and eosin and desmin
      staining. Furthermore, uterine weight and hormone levels were measured. RESULTS:
      The proportion of animals with macroscopic bicornuate decidualization was higher
      after laparoscopic (83%) and laparotomic (89%) injection than after sham
      injection (11%). Furthermore, macroscopic bicornuate decidualization was
      significantly higher after laparotomic injection (89%) compared to the vaginal
      injection (38%). Uterine weight and endometrial surface area were significantly
      higher in both laparotomy and laparoscopy groups compared to the sham group,
      while the relative desmin-positive endometrial surface area was only
      significantly different between the laparotomy and the sham animals. CONCLUSION:
      Methods using laparoscopic and laparotomic intrauterine oil injection resulted in
      a higher amount of decidualized endometrium compared to sham injection, although
      further optimization is needed to reach full bicornuate decidualization.

PMID- 29455622
TI  - Synthesis of low cost organometallic-type catalysts for their application in
      microbial fuel cell technology.
AB  - Microbial fuel cells (MFCs) are a promising technology that generates electricity
      from several biodegradable substrates and wastes. The main drawback of these
      devices is the need of using a catalyst for the oxygen reduction reaction at the
      cathode, which makes the process relatively expensive. In this work, two low cost
      materials are tested as catalysts in MFCs. A novel iron complex based on the
      ligand n-phenyledenparaethoxy aniline has been synthesized and its performance as
      catalyst in single chamber MFCs containing ionic liquids has been compared with a
      commercial inorganic material such as Raney nickel. The results show that both
      materials are suitable for bioenergy production and wastewater treatment in the
      systems. Raney nickel cathodes allow MFCs to reach a maximum power output of 160
      mW.m-3anode, while the iron complex offers lower values. Regarding the wastewater
      treatment capacity, MFCs working with Raney nickel-based cathodes reach higher
      values of chemical oxygen demand removal (76%) compared with the performance
      displayed by the cathodes based on Fe-complex (56%).

PMID- 29455623
TI  - Rare case of bilateral aural atresia and cochlear dysplasia: when cochlear
      implantation is not the answer.
AB  - OBJECTIVE AND IMPORTANCE: Reports of patients with concurrent middle and inner
      ear anomalies are rare. These patients present a surgical challenge for cochlear
      implantation. The surgical risk must be weighed against the predicted benefit of
      the patient's hearing outcome and subsequent development of speech and language
      as well as their quality of life. CLINICAL PRESENTATION: Thirteen-year-old boy
      presented to the Otology clinic for auditory rehabilitation options. He has mild
      developmental delay, is non-verbal and communicates via American Sign Language.
      He was born with bilateral aural atresia and never wore amplification. On exam he
      has grade 1 microtia and complete ear canal atresia bilaterally. His behavioural
      hearing test shows profound sensorineural hearing loss of both ears. The computed
      tomography scan shows bilateral underdeveloped and completely opacified mastoid
      and middle ear, complete bony atresia of the ear canals, and an under-partitioned
      cochlea with poorly defined modiolus, among other abnormalities. The patient and
      his family were counselled on the available options as well as the need for any
      further studies. INTERVENTION: Counselling of patient and family. CONCLUSION:
      While there have been reports in the literature of performing cochlear
      implantations in patients with a concurrent atresia and cochlear dysplasia, these
      were patients whose degree of inner ear anomalies was relatively minor and their
      prognosis of a good audiological outcome was favourable. The presented case is
      that of a patient for whom the surgical approach to the cochlea alone would be
      difficult. More importantly, his quality of life would not significantly improve
      in light of the predicted limited hearing and language development outcomes,
      given the severity of his inner ear abnormalities, limited communication
      abilities, prolonged period of deafness and developmental delays.

PMID- 29455624
TI  - Electrospinning of Polycaprolactone/Pluronic F127 dissolved in glacial acetic
      acid: fibrous scaffolds fabrication, characterization and in vitro evaluation.
AB  - Abstracts The Polycaprolactone (PCL) fibrous scaffolds in nano to micro scale
      have been considered as excellent templates for cell culture and tissue growth.
      The hydrophobic nature of the PCL, however, yields low initial cell seeding
      density, heterogeneous cell spreading and slow cell growth rate. Therefore, in
      this study the surface hydrophilic fibrous scaffolds were directly fabricated by
      the electrospinning of PCL solutions with small quantities (0.5-5%) of Pluronic
      F127 (PEO100-PPO65-PEO100) dissolved in benign solvent of glacial acetic acid.
      The clear and miscible solutions were achieved by controlling the proper F127
      content in the blend solutions. The continuous and smooth fibers with average
      diameters from 0.71 to 1.43 MUm made up the fibrous scaffolds in non-woven mode.
      Then the water wetting angle of the scaffolds could be adjusted from 126 degrees 
      to 0 degrees  by varying F127 content owing to its hydrophilic PEO chains
      presented on surface the blended fibers. Finally, it was demonstrated that the
      blended fibrous scaffolds with the F127 content less than 1% exhibited better
      cell attachment, proliferation and spreading performance than those of pure PCL
      scaffolds.

PMID- 29455625
TI  - Diarrhea caused by rotavirus A, B, and C in suckling piglets from southern
      Brazil: molecular detection and histologic and immunohistochemical
      characterization.
AB  - Rotavirus (RV) is an important viral pathogen causing diarrhea in piglets and
      other mammals worldwide. We describe 34 cases from 4 diarrheal outbreaks caused
      by RV in unvaccinated farrowing units in southern Brazil from 2011 to 2013. We
      performed autopsy, histologic examinations, bacterial culture, RV
      immunohistochemistry (IHC), and enteric virus detection through molecular assays
      for rotavirus A, B, and C, transmissible gastroenteritis virus, porcine epidemic
      diarrhea virus, sapovirus, norovirus, and kobuvirus. Histologically, villus
      atrophy (29 of 34) and epithelial vacuolation (27 of 34) occurred in all 4
      outbreaks. Cell debris in the lamina propria occurred in 20 cases, mostly from
      outbreaks A (8 of 11), C (4 of 6), and D (7 of 11). IHC was positive for RV in 21
      of 34 samples. RT-PCR was positive for RV in 20 of 30 samples; RV-C was the most
      frequently detected RV ( n = 17). Kobuvirus was detected in 11 samples, and, in 3
      of them, there was single detection of this enteric virus.

PMID- 29455626
TI  - Diagnosis of anaplastic large-cell lymphoma in a dog using CD30
      immunohistochemistry.
AB  - Anaplastic large-cell lymphoma or null-cell lymphoma is a clinical entity
      reported in people, classified according to the unique appearance of large
      pleomorphic cells that express CD30. Null-cell lymphoma has also been described
      in dogs when neither CD3 nor CD79alpha is expressed by the tumor. We describe a
      case of lymphoma in the dog in which neoplastic cells did not express routine B-
      or T-lymphocyte markers on flow cytometry or immunohistochemistry; however, cells
      immunohistochemically labeled for CD30. The dog in our case died 5 mo after
      initial presentation, confirming a poor prognosis. Identification of further
      similar cases in dogs would provide additional prognostic information for this
      subset of lymphomas. CD30 may also serve as a potential therapeutic target in
      anaplastic large-cell lymphomas.

PMID- 29455627
TI  - Gastrointestinal spindle cell tumor of the rumen with metastasis to the liver in
      a goat.
AB  - Many neoplasms have been reported in goats; however, neoplasia of the rumen is
      rarely reported. A 9-y-old castrated male pygmy goat was presented with a history
      of respiratory stertor, fever, and anorexia. A respiratory diagnostic work-up
      including skull and thorax radiographs and endoscopy revealed minor enlargement
      of the arytenoids but no other abnormal findings. After a month of little
      improvement on symptomatic treatment and worsening general health, the goat was
      euthanized. On autopsy, the forestomachs, liver, spleen, diaphragm, and the
      ventral and lateral aspects of the cranial third of the walls of the peritoneal
      cavity were adhered to one another by fibrinous and fibrous adhesions. Numerous
      firm, white, up to 2 cm diameter nodules were found throughout the liver. A large
      sessile mass extended from the rumen wall into the lumen. The rumen mass was a
      gastrointestinal stromal tumor with metastasis to the liver.

PMID- 29455628
TI  - Nga Whakawhitinga (standing at the crossroads): How Maori understand what Western
      psychiatry calls "schizophrenia".
AB  - This project explored how Maori understand experiences commonly labelled
      "schizophrenic" or "psychotic". Semi-structured interviews were conducted with 57
      Maori participants who had either personal experiences labelled as "psychosis" or
      "schizophrenia", or who work with people with such experiences; including tangata
      whaiora (users of mental health services), tohunga (traditional healers),
      kaumatua/kuia (elders), Maori clinicians, cultural support workers and students.
      Kaupapa Maori Theory and Personal Construct Theory guided the research within a
      qualitative methodology. The research found that participants held multiple
      explanatory models for experiences commonly labelled "psychotic" or
      "schizophrenic". The predominant explanations were spiritual and cultural. It
      seems that cultural beliefs and practices related to mental health within Maori
      communities remain resilient, despite over a century of contact with mainstream
      education and health services. Other explanations included psychosocial
      constructions (interpersonal trauma and drug abuse), historical trauma
      (colonisation) and biomedical constructions (chemical brain imbalance).
      Participants (both tangata whaiora and health professionals) reported they were
      apprehensive about sharing their spiritual/cultural constructions within
      mainstream mental health settings due to fear of being ignored or pathologised.
      This study highlights the importance of asking users of mental health services
      about the meaning they place on their experiences and recognising that
      individuals can hold multiple explanatory models. Maori may hold both Maori and
      Pakeha (European) ways of understanding their experiences and meaningful
      recognition should be afforded to both throughout assessment and treatment
      planning in mental health services. Clinicians need to be aware that important
      personal and cultural meanings of experiences labelled psychotic may be withheld
      due to fear of judgement or stigmatisation.

PMID- 29455629
TI  - Functional outcome of open surgical A1 pulley release in diabetic and nondiabetic
      patients.
AB  - PURPOSE: Trigger finger, also referred to as stenotic flexor tenosynovitis, is a
      common condition affecting the digits, with a lifetime incidence of 2.6% among
      the healthy population and up to 16.5% in diabetic patients. Diabetes mellitus is
      associated with multiple musculoskeletal conditions including trigger finger. In
      this study, we aimed to compare the functional outcome of trigger finger release
      in diabetic and nondiabetic patients to evaluate whether the management of
      trigger finger in diabetic patients should be the same as that in nondiabetic
      patients, or whether diabetic patients would benefit from a more tailored
      management plan to optimize results. METHODS: A retrospective case-control study
      was performed at a single center among patients who underwent A1 pulley release
      from January 2013 to February 2017. Patients were diagnosed with trigger finger
      grades I to IV according to the Quinnell classification and assessed using the
      The Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire (Arabic
      version). RESULTS: Sixty-nine patients, including 21 male (30.4%) and 48 female
      (69.6%), underwent A1 pulley release surgery. More than half of the participants
      included in this study were diabetic (n = 40, 58%) and 29 were nondiabetic (42%).
      The mean postoperative QuickDASH scores were 19.93 among diabetic patients and
      17.15 among nondiabetic patients. There was no significant difference in the
      functional outcome between diabetic and nondiabetic ( p = 0.6) patients.
      CONCLUSIONS: The postoperative functional outcomes are similar in diabetic and
      nondiabetic patients. Therefore, the management of trigger finger should be the
      same in both groups.

PMID- 29455630
TI  - Cervical endoscopic spinal surgery: A review of the current literature.
AB  - Cervical endoscopic spinal surgery (CESS) is now regularly performed in some
      centres in the Far East, yet rarely in Europe and the United States. This review
      describes the application of CESS through anterior and posterior approaches with
      analysis of the available evidence supporting current techniques. An electronic
      literature search identified 52 papers and proceedings' abstracts of which 25 (16
      anterior approach and 9 posterior approach) provided comparable clinical
      outcomes. The results revealed a good or excellent outcome from CESS in 91%
      (range 74-100%) with a complication rate of 5%. In a local cohort study, patients
      had 72% less neck pain (visual analogue scale rating) and 81% less arm pain at 6
      months when CESS was used as an isolated procedure, and 74% less neck pain and
      83% less arm pain when coupled with disc replacement or fusion at an adjacent
      level.

PMID- 29455631
TI  - Periosteal flap augmentation of the Modified Brostrom-Gould procedure for chronic
      lateral ankle instability.
AB  - INTRODUCTION: Chronic lateral ankle instability occurs in up to 20% of ankle
      injuries. Most can be treated conservatively, but surgical reconstruction is
      required if conservative treatment fails. Modified Brostrom-Gould procedure is an
      effective surgical treatment and the augmentation of this procedure with a
      periosteal flap may confer additional stability. We report on the outcome of a
      technique combining a modified Brostrom-Gould procedure augmented with a
      periosteal flap in patients with chronic lateral ankle instability. METHOD:
      Twenty-four males aged 18-42 (mean, 24) with chronic lateral ankle instability
      affecting 24 ankles underwent the modified Brostrom-Gould procedure augmented
      with a periosteal flap, and these surgeries were performed by a single surgeon.
      The mean follow-up period was 28.7 months. Patients were assessed pre- and post
      operatively with the American Orthopaedic Foot and Ankle Society (AOFAS) ankle
      and hind foot score. RESULTS: Preoperatively, the mean AOFAS ankle and hind foot
      score was 67.38. Post-operatively, significant improvement was seen, with a score
      of 88.71 ( p < 0.05). None of the patients reported surgical or wound
      complications. CONCLUSION: The technique of modified Brostrom-Gould procedure
      with periosteal flap augmentation appears to be a simple and safe operation for
      chronic lateral ankle instability. Patients with poor quality local ligamentous
      tissue, obese patients or high demand athletes generally benefit from this
      procedure. It allows effective augmentation of the reconstruction without causing
      any harm to local tendons or using additional costly implants.

PMID- 29455632
TI  - Arthroscopic undersurface rotator cuff repair versus conventional arthroscopic
      double-row rotator cuff repair - Comparable results at 2-year follow-up.
AB  - AIM: The aim of our study is to compare the improvement in clinical outcomes
      after conventional arthroscopic double-row rotator cuff repair and arthroscopic
      undersurface rotator cuff repair. METHOD: A consecutive series of 120 patients
      who underwent arthroscopic rotator cuff repair was analysed. Sixty-one patients
      underwent conventional double-row rotator cuff repair and 59 patients underwent
      undersurface rotator cuff repair. Several clinical outcomes, including numerical
      pain rating scale (NPRS), constant shoulder score (CSS), Oxford shoulder score
      (OSS) and University of California Los Angeles shoulder score (UCLASS), were
      prospectively recorded by a trained healthcare professional preoperatively and at
      3, 6, 12 and 24 months after surgery. RESULT: Comparing both groups, there were
      no differences in age, gender and preoperative NPRS, CSS, OSS and UCLASS.
      However, the tear size was 0.7 +/- 0.2 (95% confidence interval (CI) 0.3-1.1) cm
      larger in the conventional group ( p = 0.002). There was no difference in the
      improvement of NPRS, CSS, OSS and UCLASS at all time points of follow-up, that
      is, at 3, 6, 12 and 24 months after surgery. The duration of operation was
      shorter by 35 +/- 3 (95% CI 28-42) min in the undersurface group ( p < 0.001).
      CONCLUSION: Both arthroscopic undersurface rotator cuff repair and conventional
      arthroscopic double-row rotator cuff repair showed marked improvements in
      clinical scores when compared preoperatively, and there was no difference in
      improvements between both groups. Arthroscopic undersurface rotator cuff repair
      is a faster technique compared to the conventional arthroscopic double-row
      rotator cuff repair.

PMID- 29455633
TI  - Placental growth factor, vascular endothelial growth factor, and hypoxia
      inducible factor-1alpha in the placentas of women with pre-eclampsia.
AB  - BACKGROUND: Although the exact mechanism of pre-eclampsia - high blood pressure
      and proteinuria after 20 gestational weeks - is not yet fully understood,
      placental growth factor (PLGF), vascular endothelial growth factor (VEGF), and
      hypoxia-inducible factor (HIF) are known to play important roles in
      vascularization and in the pathology of pre-eclampsia. METHODS: PLGF, VEGF, and
      HIF-1alpha were evaluated by immunohistochemistry in the placentas of Sudanese
      women with mild or severe pre-eclampsia, and in normal controls. RESULTS: Sixty
      two women had severe pre-eclampsia, 102 had mild pre-eclampsia and 101 women
      served as healthy controls. Immunohistochemical staining of PLGF was
      significantly lower in placentas of women with severe pre-eclampsia (16%)
      compared with those with mild pre-eclampsia (8.8%) and placentas of normotensive
      women (40.6%; p < .001). Significantly more of the pre-eclamptic placentas
      expressed VEGF: in 32%, 17.6%, and 14.9% (p = .020) of the placentas of women
      with severe or mild pre-eclampsia and in controls, respectively. Significantly
      more of the pre-eclamptic placentas expressed HIF-1alpha: in 15%, 10.8%, and 5.0%
      of the placentas of women with severe or mild pre-eclampsia, and in controls,
      respectively (p = .044). CONCLUSION: The current study showed that PLGF, VEGF,
      and HIF-1alpha are involved in the pathophysiology of pre-eclampsia.

PMID- 29455634
TI  - Early Predictors of Global Functional Outcome after Traumatic Spinal Cord Injury:
      A Systematic Review.
AB  - Accurately predicting functional recovery is an asset for all clinicians and
      decision makers involved in the care of patients with acute traumatic spinal cord
      injury (TSCI). Unfortunately, there is a lack of information on the relative
      importance of significant predictors of global functional outcome. There is also
      a need for identifying functional predictors that can be timely optimized by the
      medical and rehabilitation teams throughout the hospitalizations phases. The main
      objective of this work was to systematically review and rate early factors that
      are consistently and independently associated with global functional outcome in
      individuals with TSCI. A literature search using MEDLINE, EMBASE, and Cochrane
      databases from January 1, 1970 to April 1, 2017 was performed. Two authors
      independently reviewed the titles and abstracts yielded by this literature search
      and subsequently selected studies to be included based on predetermined
      eligibility criteria. Disagreements were resolved by a consensus-based
      discussion, and if not, by an external reviewer. Data were extracted by three
      independent reviewers using a standardized table. The quality of evidence of the
      individual studies was assessed based on the Oxford Center for Evidence-Based
      Medicine modified by Wright and colleagues (2000) as well as the National
      Institutes of Health (2014). Fifteen articles identifying early clinical
      predictors of functional outcome using multiple regression analyses were included
      in this systematic review. Based on the compiled data, this review proposes a
      rating of early factors associated to global functional outcome according to
      their importance and their potential to be modified by the medical/rehabilitation
      team throughout the early phases of hospitalization. It also proposes a new
      conceptual framework that illustrates the impact of specific categories of
      factors and their interaction with each other. Ultimately, this review aims to
      guide clinicians and researchers in improving the continuum of care throughout
      early phases post-SCI.

PMID- 29455635
TI  - The efficacy and safety of methotrexate versus interferon in cutaneous T-cell
      lymphomas.
AB  - OBJECTIVES: Methotrexate (MTX) and interferon (IFN) have been used in the
      treatment of cutaneous T-cell lymphomas (CTCL) of various subtypes. We review our
      experience of MTX and IFN use in our patients with CTCL at a tertiary hospital.
      MATERIALS AND METHODS: Medical records of patients over 4 years were reviewed. We
      describe the dosages, time to response, response rates, side effects, progression
      rate, and reasons for discontinuation. RESULTS: Response rate was significantly
      higher in the IFN group than MTX group (86.67% and 47.4% respectively, p = .01).
      Disease progression occurred 57.89% in the MTX group whilst only 26.67%
      progressed with IFN therapy. Patients taking IFN therapy experienced
      proportionally more side effects of any type than those undertaking MTX treatment
      (86.67% vs. 47.37%, odds ratio 7.22). However, discontinuation rate in the IFN
      group (26.67%) was much lower than in the MTX arm (89.47%). CONCLUSIONS: The most
      significant finding of this study was that patients with CTCL treated with IFN
      had a better response rate and significantly shorter response time compared with
      those treated with MTX. Additionally, patients had less disease progression on
      IFN than with MTX regardless of subtype of T-cell lymphoma and stage of disease.

PMID- 29455636
TI  - Feasibility investigation of a multi soil layering bioreactor for domestic
      wastewater treatment.
AB  - In this study, a multi soil layering (MSL) bioreactor was constructed to treat
      synthetic domestic wastewater. Effects of hydraulic loading rate (HLR) on the
      performance of the MSL bioreactor for synthetic domestic wastewater treatment
      were investigated. Results showed that the MSL bioreactor exhibited a strong
      adaptability on the variation of HLR, when the HLR was adjusted to 400 L.m-2.d-1,
      average removal efficiencies of chemical oxygen demand (COD), ammonia, total
      nitrogen (TN), and total phosphorus (TP) reached 93.4%, 94.9%, 80.4%, and 94.7%,
      respectively, which meet to the 1A discharge standard of the Discharge standard
      of pollutants for municipal wastewater treatment plant (GB 18918-2002). In the
      treatment process by the MSL bioreactor, biological decomposition and
      biotransformation processes of microorganisms was the most important pathway for
      COD, ammonia, and TN removal, while TP was removed by the chemical reaction with
      ferric ion. Nitrobacteria, ciliate, rotifer and epistylis were in large numbers
      in the operating phase, indicated that the biofilm was matured with a high
      quality and the MSL bioreactor was effective for domestic wastewater treatment.

PMID- 29455637
TI  - Molecular dynamics of interaction of Sesamin and related compounds with the
      cancer marker beta-catenin: an in silico study.
AB  - By virtue of their regulatory role in the biological process, certain protein
      protein complexes form potential targets for designing and discovery of drugs.
      Alteration set in the controlled formation of such complexes results in
      dysregulation of several metabolic processes, leading to diseased condition. beta
      catenin/Tcf4 complex is one such protein-protein complex found altered in
      colorectal epithelial cells resulting in activation of target genes leading to
      cancer. Recently, certain lignans from seeds of the oil crop sesame were found
      inhibiting initiation and progression of this type of cancer. Molecular mechanism
      involved in the process, however, is not yet known. By an in silico study, we
      present here a possible mechanism of interaction between the sesame lignans and
      beta-catenin leading to inhibition of formation of the said complex, thereby
      elevating some of these ligands as potential lead molecules in the development of
      drugs for treatment of colon cancer. To achieve this objective, we performed
      docking, molecular dynamics simulation, and binding free energy analysis of
      target-ligand complexes. Using computational alanine scanning approach, the key
      pocket residues of beta-catenin that interact with Tcf4 in the formation of
      complex were identified. The test molecules were initially evaluated for their
      drug-like properties by application of Lipinski's rule of five. Results of this
      study revealed that Sesamin, a furofuran lignan from sesame, has the highest
      affinity for beta-catenin particularly with its residues that interact with Tcf4
      and thus serving as a potential lead molecule for development of a drug for colon
      cancer.

PMID- 29455638
TI  - Clinicopathologic and Prognostic Significance of Programmed Cell Death Ligand 1
      Expression in Patients with Non-Medullary Thyroid Cancer: A Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND: Evidence has shown that programmed cell death ligand 1 (PD-L1)
      overexpression is associated with poor prognosis and resistance to immune
      therapies in several human cancers. However, data on the prognostic significance
      of PD-L1 expression in thyroid cancer are limited and remain controversial. This
      systematic review and meta-analysis aimed to evaluate comprehensively the
      clinicopathologic significance and prognostic value of PD-L1 expression in non
      medullary thyroid cancers. METHODS: Electronic databases, including
      Medline/PubMed, EMBASE, and the Cochrane Library, were searched up until July 5,
      2017. In total, seven comparisons (from six articles) comprising 1421 patients
      were included in the pooled analysis. RESULTS: There was moderate quality
      evidence from four studies (n = 721) that shows positive PD-L1 expression was
      significantly associated with poor survival among thyroid cancer patients (pooled
      hazard ratio = 3.73 [confidence interval (CI) 2.75-5.06]). Increased PD-L1
      expression was also found to be significantly associated with disease recurrence
      (odds ratio = 1.95 [CI 1.15-3.32]) and concurrent thyroiditis (odds ratio = 1.65
      [CI 1.09-2.51]). CONCLUSIONS: The results confirm the prognostic significance of
      PD-L1 expression in thyroid cancer patients. PD-L1 expression has the potential
      to be implemented as a prognostic biomarker used to guide clinicians in
      identifying patients with more aggressive cancers, and for the selection of
      individuals that would derive durable clinical benefit from anti-PD-1/PD-L1
      immunotherapy. Prospective clinical trials will be useful to support these
      findings.

PMID- 29455640
TI  - CCL2/CCL5 secreted by the stroma induce IL-6/PYK2 dependent chemoresistance in
      ovarian cancer.
AB  - BACKGROUND: Minimal residual disease is the main issue of advanced ovarian cancer
      treatment. According to the literature and previous results, we hypothesized that
      Mesenchymal Stromal Cells (MSC) could support this minimal residual disease by
      protecting ovarian cancer cells (OCC) from chemotherapy. In vitro study confirmed
      that MSC could induce OCC chemoresistance without contact using transwell
      setting. Further experiments showed that this induced chemoresistance was
      dependent on IL-6 OCC stimulation. METHODS: We combined meticulous in vitro
      profiling and tumor xenograft models to study the role of IL-6 in MSC/OCC
      intereactions. RESULTS: We demonstrated that Tocilizumab(r) (anti-IL-6R therapy)
      in association with chemotherapy significantly reduced the peritoneal carcinosis
      index (PCI) than chemotherapy alone in mice xenografted with OCCs+MSCs. Further
      experiments showed that CCL2 and CCL5 are released by MSC in transwell co-culture
      and induce OCCs IL-6 secretion and chemoresistance. Finally, we found that IL-6
      induced chemoresistance was dependent on PYK2 phosphorylation. CONCLUSIONS: These
      findings highlight the potential key role of the stroma in protecting minimal
      residual disease from chemotherapy, thus favoring recurrences. Future clinical
      trials targeting stroma could use anti-IL-6 therapy in association with
      chemotherapy.

PMID- 29455641
TI  - Circadian pathway genetic variation and cancer risk: evidence from genome-wide
      association studies.
AB  - BACKGROUND: Dysfunction of the circadian clock and single polymorphisms of some
      circadian genes have been linked to cancer susceptibility, although data are
      scarce and findings inconsistent. We aimed to investigate the association between
      circadian pathway genetic variation and risk of developing common cancers based
      on the findings of genome-wide association studies (GWASs). METHODS: Single
      nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta
      analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants
      in Breast Cancer (DRIVE) Consortium; cases, n = 15,748; controls, n = 18,084),
      prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE)
      Consortium; cases, n = 14,160; controls, n = 12,724) and lung carcinoma
      (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n =
      12,160; controls, n = 16,838) in patients of European ancestry were utilized to
      perform pathway analysis by means of the adaptive rank truncated product (ARTP)
      method. Data were also available for the following subgroups: estrogen receptor
      negative breast cancer, aggressive prostate cancer, squamous lung carcinoma and
      lung adenocarcinoma. RESULTS: We found a highly significant statistical
      association between circadian pathway genetic variation and the risk of breast
      (pathway P value = 1.9 * 10-6; top gene RORA, gene P value = 0.0003), prostate
      (pathway P value = 4.1 * 10-6; top gene ARNTL, gene P value = 0.0002) and lung
      cancer (pathway P value = 6.9 * 10-7; top gene RORA, gene P value = 2.0 * 10-6),
      as well as all their subgroups. Out of 17 genes investigated, 15 were found to be
      significantly associated with the risk of cancer: four genes were shared by all
      three malignancies (ARNTL, CLOCK, RORA and RORB), two by breast and lung cancer
      (CRY1 and CRY2) and three by prostate and lung cancer (NPAS2, NR1D1 and PER3),
      whereas four genes were specific for lung cancer (ARNTL2, CSNK1E, NR1D2 and PER2)
      and two for breast cancer (PER1, RORC). CONCLUSIONS: Our findings, based on the
      largest series ever utilized for ARTP-based gene and pathway analysis, support
      the hypothesis that circadian pathway genetic variation is involved in cancer
      predisposition.

PMID- 29455639
TI  - Role of Bruton's tyrosine kinase in B cells and malignancies.
AB  - Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role
      in oncogenic signaling that is critical for proliferation and survival of
      leukemic cells in many B cell malignancies. BTK was initially shown to be
      defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and
      is essential both for B cell development and function of mature B cells. Shortly
      after its discovery, BTK was placed in the signal transduction pathway downstream
      of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of
      this kinase have shown excellent anti-tumor activity, first in animal models and
      subsequently in clinical studies. In particular, the orally administered
      irreversible BTK inhibitor ibrutinib is associated with high response rates in
      patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and mantle
      cell lymphoma (MCL), including patients with high-risk genetic lesions. Because
      ibrutinib is generally well tolerated and shows durable single-agent efficacy, it
      was rapidly approved for first-line treatment of patients with CLL in 2016. To
      date, evidence is accumulating for efficacy of ibrutinib in various other B cell
      malignancies. BTK inhibition has molecular effects beyond its classic role in BCR
      signaling. These involve B cell-intrinsic signaling pathways central to cellular
      survival, proliferation or retention in supportive lymphoid niches. Moreover, BTK
      functions in several myeloid cell populations representing important components
      of the tumor microenvironment. As a result, there is currently a considerable
      interest in BTK inhibition as an anti-cancer therapy, not only in B cell
      malignancies but also in solid tumors. Efficacy of BTK inhibition as a single
      agent therapy is strong, but resistance may develop, fueling the development of
      combination therapies that improve clinical responses. In this review, we discuss
      the role of BTK in B cell differentiation and B cell malignancies and highlight
      the importance of BTK inhibition in cancer therapy.

PMID- 29455642
TI  - Role and targeting of anaplastic lymphoma kinase in cancer.
AB  - Anaplastic lymphoma kinase (ALK) gene activation is involved in the
      carcinogenesis process of several human cancers such as anaplastic large cell
      lymphoma, lung cancer, inflammatory myofibroblastic tumors and neuroblastoma, as
      a consequence of fusion with other oncogenes (NPM, EML4, TIM, etc) or gene
      amplification, mutation or protein overexpression. ALK is a transmembrane
      tyrosine kinase receptor that, upon ligand binding to its extracellular domain,
      undergoes dimerization and subsequent autophosphorylation of the intracellular
      kinase domain. When activated in cancer it represents a target for specific
      inhibitors, such as crizotinib, ceritinib, alectinib etc. which use has
      demonstrated significant effectiveness in ALK-positive patients, in particular
      ALK-positive non- small cell lung cancer. Several mechanisms of resistance to
      these inhibitors have been described and new strategies are underway to overcome
      the limitations of current ALK inhibitors.

PMID- 29455644
TI  - miR-19b enhances proliferation and apoptosis resistance via the EGFR signaling
      pathway by targeting PP2A and BIM in non-small cell lung cancer.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutations enable constitutive
      active downstream signaling of PI3K/AKT, KRAS/ERK and JAK/STAT pathways, and
      promote tumor progression by inducing uncontrolled proliferation, evasion of
      apoptosis and migration of non-small cell lung cancer (NSCLC). In addition, such
      EGFR mutations increase the susceptibility of patients with NSCLC to tyrosine
      kinase inhibitor (TKI) therapy, but treated patients will invariably relapse with
      resistant disease. A global understanding of underlying molecular mechanisms of
      EGFR signaling may improve the management of NSCLC patients. METHODS: microarray
      analysis was performed to identify PI3K/AKT-regulated miRNAs. Phosphoproteomic
      analysis and cell based assays were performed using NSCLC cell lines lentivirally
      transduced with anti-miR or miR overexpressing constructs. RESULTS: Here, we show
      that 17 miRNAs including members of the miR-17~ 92 cluster are dysregulated
      following PI3K/AKT inhibition of EGFR mutant NSCLC cells. Bioinformatics analysis
      revealed that dysregulated miRNAs act in a concerted manner to enhance the
      activity of the EGFR signaling pathway. These findings were closely mirrored by
      attenuation of miR-17~ 92 family member miR-19b in NSCLC cell lines which
      resulted in reduced phosphorylation of ERK, AKT and STAT and effector proteins in
      EGFR mutant NSCLC cells. Consistent with this finding, cell cycle progression,
      clonogenic growth and migration were reduced and apoptosis was enhanced. Co
      treatment of NSCLC cells with the tyrosine kinase inhibitor (TKI) gefitinib and
      anti-miR-19b construct reduced migration and clonogenic growth in a synergistic
      manner suggesting that EGFR and miR-19b act together to control oncogenic
      processes. Serine/threonine phosphatase PP2A subunit PPP2R5E and BCL2L11 encoding
      BIM were identified as major targets of miR-19b by target validation assays.
      Consistent with this finding, PP2A activity was strongly enhanced in NSCLC
      transduced with anti-miR-19b construct, but not in cells co-transduced with anti
      miR-19b and shPPP2R5E, suggesting that PPP2R5E is a major constituent of the PP2A
      complex. Accordingly, enhanced proliferation by miR-19b was due to targeting
      PPP2R5E. In contrast, apoptosis resistance was mainly due to targeting BCL2L11.
      CONCLUSION: Our results provide insight into the importance of targeting PPP2R5E
      and BCL2L11 by miR-19b in oncogenic processes of NSCLC. Attenuation of miR-19b
      expression could potentially be exploited in adjuvant therapy of EGFR mutant
      NSCLC.

PMID- 29455643
TI  - Chronic myeloid leukemia: the paradigm of targeting oncogenic tyrosine kinase
      signaling and counteracting resistance for successful cancer therapy.
AB  - Deregulated activity of BCR-ABL1, a nonreceptor tyrosine kinase encoded by the
      fusion gene resulting from the t(9;22)(q34;q11) chromosomal translocation, is
      thought to be the driver event responsible for initiation and maintenance of
      chronic myeloid leukemia (CML). BCR-ABL1 was one of the first tyrosine kinases to
      be implicated in a human malignancy and the first to be successfully targeted.
      Imatinib mesylate, the first tyrosine kinase inhibitor (TKI) to be approved for
      therapeutic use, was hailed as a magic bullet against cancer and remains one of
      the safest and most effective anticancer agents ever developed. Second- and third
      generation TKIs were later introduced to prevent or counteract the problem of
      drug resistance, that may arise in a small proportion of patients. They are more
      potent molecules, but have been associated to more serious side effects and
      complications. Patients achieving stable optimal responses to TKI therapy are
      predicted to have the same life expectancy of the general population. However,
      TKIs do not 'cure' CML. Only a small proportion of cases may attempt therapy
      discontinuation without experiencing subsequent relapse. The great majority of
      patients will have to assume TKIs indefinitely - which raises serious
      pharmacoeconomic concerns and is now shifting the focus from efficacy to
      compliance and quality of life issues. Here we retrace the steps that have led
      from the biological acquisitions regarding BCR-ABL1 structure and function to the
      development of inhibitory strategies and we discuss drug resistance mechanism and
      how they can be addressed.

PMID- 29455645
TI  - Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular
      metabolism, transcriptional regulation to extracellular signaling.
AB  - Originally identified as a metabolic enzyme that catalyzes the transfer of a
      phosphate group from phosphoenolpyruvate (PEP) to ADP in the glycolytic pathway,
      pyruvate kinase M2-type (PKM2) has been shown to exhibit novel biological
      activities in the nucleus and outside the cells. Although cell-based studies
      reveal new non-canonical functions of PKM2 in gene transcription, epigenetic
      modulation and cell cycle progression, the importance of these non-canonical
      functions in PKM2-mediated tumorigenesis is still under debate because studies in
      genetically modified mice do not consistently echo the findings observed in
      cultured cancer cells. In addition to regulation of gene expression, the
      existence of PKM2 in exosomes opens a new venue to study the potential role of
      this glycolytic enzyme in cell-cell communication and extracellular signal
      initiation. In this review, we briefly summarize current understanding of PKM2 in
      metabolic switch and gene regulation. We will then emphasize recent progress of
      PKM2 in extracellular signaling and tumor microenvironment reprogramming.
      Finally, the discrepancy of some PKM2's functions in vitro and in vivo, and the
      application of PKM2 in cancer detection and treatment will be discussed.

PMID- 29455646
TI  - Tyrosine kinase inhibitors enhanced the efficacy of conventional chemotherapeutic
      agent in multidrug resistant cancer cells.
AB  - Multidrug resistance (MDR) triggered by ATP binding cassette (ABC) transporter
      such as ABCB1, ABCC1, ABCG2 limited successful cancer chemotherapy.
      Unfortunately, no commercial available MDR modulator approved by FDA was used in
      clinic. Tyrosine kinase inhibitors (TKIs) have been administrated to fight
      against cancer for decades. Almost TKI was used alone in clinic. However, drug
      combinations acting synergistically to kill cancer cells have become increasingly
      important in cancer chemotherapy as an approach for the recurrent resistant
      disease. Here, we summarize the effect of TKIs on enhancing the efficacy of
      conventional chemotherapeutic drug in ABC transporter-mediated MDR cancer cells,
      which encourage to further discuss and study in clinic.

PMID- 29455647
TI  - 99mTc-HYNIC-(tricine/EDDA)-FROP peptide for MCF-7 breast tumor targeting and
      imaging.
AB  - BACKGROUND: Breast cancer is the most common malignancy among women in the world.
      Development of novel tumor-specific radiopharmaceuticals for early breast tumor
      diagnosis is highly desirable. In this study we developed 99mTc-HYNIC
      (tricine/EDDA)-Lys-FROP peptide with the ability of specific binding to MCF-7
      breast tumor. METHODS: The FROP-1 peptide was conjugated with the bifunctional
      chelator hydrazinonicotinamide (HYNIC) and labeled with 99mTc using tricine/EDDA
      co-ligand. The cellular specific binding of 99mTc-HYNIC-FROP was evaluated on
      different cell lines as well as with blocking experiment on MCF-7 (human breast
      adenocarcinoma). The tumor targeting and imaging of this labeled peptide were
      performed on MCF-7 tumor bearing mice. RESULTS: Radiochemical purity for 99mTc
      HYNIC-(tricine/EDDA)-FROP was 99% which was determined with ITLC method. This
      radiolabeled peptide showed high stability in normal saline and serum about 98%
      which was monitored with HPLC method. In saturation binding experiments, the
      binding constant (Kd) to MCF-7 cells was determined to be 158 nM. Biodistribution
      results revealed that the 99mTc-HYNIC-FROP was mainly exerted from urinary route.
      The maximum tumor uptake was found after 30 min post injection (p.i.); however
      maximum tumor/muscle ratio was seen at 15 min p.i. The tumor uptake of this
      labeled peptide was specific and blocked by co-injection of excess FROP.
      According to the planar gamma imaging result, tumor was clearly visible due to
      the tumor uptake of 99mTc-HYNIC-(tricine/EDDA)-FROP in mouse after 15 min p.i.
      CONCLUSIONS: The 99mTc-HYNIC-(tricine/EDDA)-FROP is considered a promising probe
      with high specific binding to MCF-7 breast cancer cells.

PMID- 29455649
TI  - Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based
      prognostic model for distant metastasis.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic
      cancer, with diverse molecular characteristics and clinical outcomes. This study
      aims to dissect the molecular heterogeneity of NPC, followed by the construction
      of a microRNA (miRNA)-based prognostic model for prediction of distant
      metastasis. METHODS: We retrieved two NPC datasets: GSE32960 and GSE70970 as
      training and validation cohorts, respectively. Consensus clustering was employed
      for cluster discovery, and support vector machine was used to build a classifier.
      Finally, Cox regression analysis was applied to constructing a prognostic model
      for predicting risk of distant metastasis. RESULTS: Three NPC subtypes
      (immunogenic, classical and mesenchymal) were identified that are molecularly
      distinct and clinically relevant, of which mesenchymal subtype (~ 36%) is
      associated with poor prognosis, characterized by suppressing tumor suppressor
      miRNAs and the activation of epithelial--mesenchymal transition. Out of the 25
      most differentially expressed miRNAs in mesenchymal subtype, miR-142, miR-26a,
      miR-141 and let-7i have significant prognostic power (P < 0.05). CONCLUSIONS: We
      proposed for the first time that NPC can be stratified into three subtypes. Using
      a panel of 4 miRNAs, we established a prognostic model that can robustly stratify
      NPC patients into high- and low- risk groups of distant metastasis.

PMID- 29455648
TI  - Mechanisms of receptor tyrosine kinase activation in cancer.
AB  - Receptor tyrosine kinases (RTKs) play an important role in a variety of cellular
      processes including growth, motility, differentiation, and metabolism. As such,
      dysregulation of RTK signaling leads to an assortment of human diseases, most
      notably, cancers. Recent large-scale genomic studies have revealed the presence
      of various alterations in the genes encoding RTKs such as EGFR, HER2/ErbB2, and
      MET, amongst many others. Abnormal RTK activation in human cancers is mediated by
      four principal mechanisms: gain-of-function mutations, genomic amplification,
      chromosomal rearrangements, and / or autocrine activation. In this manuscript, we
      review the processes whereby RTKs are activated under normal physiological
      conditions and discuss several mechanisms whereby RTKs can be aberrantly
      activated in human cancers. Understanding of these mechanisms has important
      implications for selection of anti-cancer therapies.

PMID- 29455650
TI  - Management of acquired resistance to EGFR TKI-targeted therapy in advanced non
      small cell lung cancer.
AB  - Recent advances in diagnosis and treatment are enabling a more targeted approach
      to treating lung cancers. Therapy targeting the specific oncogenic driver
      mutation could inhibit tumor progression and provide a favorable prognosis in
      clinical practice. Activating mutations of epidermal growth factor receptor
      (EGFR) in non-small cell lung cancer (NSCLC) are a favorable predictive factor
      for EGFR tyrosine kinase inhibitors (TKIs) treatment. For lung cancer patients
      with EGFR-exon 19 deletions or an exon 21 Leu858Arg mutation, the standard first
      line treatment is first-generation (gefitinib, erlotinib), or second-generation
      (afatinib) TKIs. EGFR TKIs improve response rates, time to progression, and
      overall survival. Unfortunately, patients with EGFR mutant lung cancer develop
      disease progression after a median of 10 to 14 months on EGFR TKI. Different
      mechanisms of acquired resistance to first-generation and second-generation EGFR
      TKIs have been reported. Optimal treatment for the various mechanisms of acquired
      resistance is not yet clearly defined, except for the T790M mutation. Repeated
      tissue biopsy is important to explore resistance mechanisms, but it has
      limitations and risks. Liquid biopsy is a valid alternative to tissue re-biopsy.
      Osimertinib has been approved for patients with T790M-positive NSCLC with
      acquired resistance to EGFR TKI. For other TKI-resistant mechanisms, combination
      therapy may be considered. In addition, the use of immunotherapy in lung cancer
      treatment has evolved rapidly. Understanding and clarifying the biology of the
      resistance mechanisms of EGFR-mutant NSCLC could guide future drug development,
      leading to more precise therapy and advances in treatment.

PMID- 29455651
TI  - Targeting few to help hundreds: JAK, MAPK and ROCK pathways as druggable targets
      in atypical chronic myeloid leukemia.
AB  - Atypical Chronic Myeloid Leukemia (aCML) is a myeloproliferative neoplasm
      characterized by neutrophilic leukocytosis and dysgranulopoiesis. From a genetic
      point of view, aCML shows a heterogeneous mutational landscape with mutations
      affecting signal transduction proteins but also broad genetic modifiers and
      chromatin remodelers, making difficult to understand the molecular mechanisms
      causing the onset of the disease. The JAK-STAT, MAPK and ROCK pathways are known
      to be responsible for myeloproliferation in physiological conditions and to be
      aberrantly activated in myeloproliferative diseases. Furthermore, experimental
      evidences suggest the efficacy of inhibitors targeting these pathways in
      repressing myeloproliferation, opening the way to deep clinical investigations.
      However, the activation status of these pathways is rarely analyzed when genetic
      mutations do not occur in a component of the signaling cascade. Given that
      mutations in functionally unrelated genes give rise to the same pathology, it is
      tempting to speculate that alteration in the few signaling pathways mentioned
      above might be a common feature of pathological myeloproliferation. If so,
      targeted therapy would be an option to be considered for aCML patients.

PMID- 29455652
TI  - Expression, regulation and targeting of receptor tyrosine kinases in esophageal
      squamous cell carcinoma.
AB  - Esophageal cancer is one of the most common types of cancer, which is a leading
      cause of cancer-related death worldwide. Based on histological behavior, it is
      mainly of two types (i) Esophageal squamous cell carcinoma (ESCC), and (ii)
      esophageal adenocarcinoma (EAD or EAC). In astronomically immense majority of
      malignancies, receptor tyrosine kinases (RTKs) have been kenned to play a
      consequential role in cellular proliferation, migration, and metastasis of the
      cells. The post-translational modifications (PTMs) including phosphorylation of
      tyrosine (pY) residue of the tyrosine kinase (TK) domain have been exploited for
      treatment in different malignancies. Lung cancer where pY residues of EGFR have
      been exploited for treatment purpose in lung adenocarcinoma patients, but we do
      not have such kind of felicitously studied and catalogued data in ESCC patients.
      Thus, the goal of this review is to summarize the studies carried out on ESCC to
      explore the role of RTKs, tyrosine kinase inhibitors, and their pertinence and
      consequentiality for the treatment of ESCC patients.

PMID- 29455654
TI  - Third generation EGFR TKIs: current data and future directions.
AB  - Acquired T790 M mutation is the commonest cause of resistance for advanced non
      small cell lung cancer (NSCLC) epidermal growth factor receptor (EGFR) mutant
      patients who had progressed after first line EGFR TKI (tyrosine kinase
      inhibitor). Several third generation EGFR TKIs which are EGFR mutant selective
      and wild-type (WT) sparing were developed to treat these patients with T790 M
      acquired resistant mutation. Osimertinib is one of the third generation EGFR TKIs
      and is currently the most advanced in clinical development. Unfortunately,
      despite good initial response, patients who was treated with third generation
      EGFR TKI would develop acquired resistance and several mechanisms had been
      identified and the commonest being C797S mutation at exon 20. Several novel
      treatment options were being developed for patients who had progressed on third
      generation EGFR TKI but they are still in the early phase of development.
      Osimertinib under FLAURA study had been shown to have better progression-free
      survival over first generation EGFR TKI in the first line setting and likely will
      become the new standard of care.

PMID- 29455653
TI  - Novel targeted therapies and immunotherapy for advanced thyroid cancers.
AB  - Thyroid cancer is a frequently encountered endocrine malignancy. Despite the
      favorable prognosis of this disease, 15-20% of differentiated thyroid cancer
      (DTC) cases and most anaplastic types, remain resistant to standard treatment
      options, including radioactive iodine (RAI). In addition, around 30% of medullary
      thyroid cancer (MTC) cases show resistance after surgery. The evolving
      understanding of disease-specific molecular therapeutic targets has led to the
      approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory
      DTC and another two drugs (Vandetanib and Cabozantinib) for MTC. These advanced
      therapies exert their effects by blocking the MAPK pathway, which has been widely
      correlated to different types of thyroid cancers. While these drugs remain
      reserved for thyroid cancer patients who failed all treatment options, their
      ability to improve patients' overall survival remain hindered by their low
      efficacy and other molecular factors. Among these factors is the tumor's ability
      to activate parallel proliferative signaling pathways other than the cascades
      blocked by these drugs, along with overexpression of some tyrosine kinase
      receptors (TKR). These facts urge the search for novel different treatment
      strategies for advanced thyroid cases beyond these drugs. Furthermore, the
      growing knowledge of the dynamic immune system interaction with tumor
      microenvironment has revolutionized the cancer immune therapy field. In this
      review, we aim to discuss the molecular escape mechanisms of thyroid tumors from
      these drugs. We also highlight novel therapeutic options targeting other pathways
      than MAPK, including PI3K pathway, ALK translocations and HER2/3 receptors and
      their clinical impact. We also aim to discuss the usage of targeted therapy in
      restoring thyroid tumor sensitivity to RAI, and finally turn to extensively
      discuss the role of immunotherapy as a potential alternative treatment option for
      advanced thyroid diseases.

PMID- 29455655
TI  - Disruption of ETV6 leads to TWIST1-dependent progression and resistance to
      epidermal growth factor receptor tyrosine kinase inhibitors in prostate cancer.
AB  - BACKGROUND: ETS variant gene 6 (ETV6) is a putative tumor suppressor and
      repressed by epidermal growth factor receptor (EGFR) signaling in prostate
      cancer. Since EGFR antagonists seem ineffective in castration-resistant prostate
      cancer (CRPC), we aim to study the role of ETV6 in the development of drug
      resistance. METHODS: Etv6 target gene was validated by ChIP and promoter reporter
      assays. Correlation of ETV6 and TWIST1 was analyzed in human clinical datasets
      and tissue samples. Migration, invasion, and metastasis assays were used to
      measure the cellular responses after perturbation of ETV6 -TWIST1 axis.
      Proliferation and tumor growth in xenograft model were performed to evaluate the
      drug sensitivities of EGFR-tyrosine kinase inhibitors (TKIs). RESULTS: ETV6
      inhibits TWIST1 expression and disruption of ETV6 promotes TWIST1-dependent
      malignant phenotypes. Importantly, ETV6 is required to the anti-proliferation
      effects of EGFR-TKIs, partly due to the inhibitory function of ETV6 on TWIST1. We
      also found that EGFR-RAS signaling is tightly controlled by ETV6, supporting its
      role in TKI sensitivity. CONCLUSIONS: Our study demonstrates that disruption of
      ETV6 contributes to EGFR-TKI resistance, which is likely due to derepression of
      TWIST1 and activation of EGFR-RAS signaling. Our results implicate ETV6 as a
      potential marker for predicting efficacy of an EGFR-targeted anticancer approach.
      Combination treatment of TWIST1 inhibitors could sensitize the anti-proliferation
      effects of EGFR-TKIs.

PMID- 29455656
TI  - The E3 ubiquitin ligase NEDD4 mediates cell migration signaling of EGFR in lung
      cancer cells.
AB  - BACKGROUND: EGFR-dependent cell migration plays an important role in lung cancer
      progression. Our previous study observed that the HECT E3 ubiquitin ligase NEDD4
      is significantly correlated with tumor metastasis and required for migration and
      invasion signaling of EGFR in gastric cancer cells. However, how NEDD4 promotes
      the EGFR-dependent lung cancer cell migration is unknown. This study is to
      elucidate the mechanism by which NEDD4 mediates the EGFR lung cancer migration
      signaling. METHODS: Lentiviral vector-loaded NEDD4 shRNA was used to deplete
      endogenous NEDD4 in lung cancer cell lines. Effects of the NEDD4 knockdown on the
      EGFR-dependent or independent lung cancer cell migration were determined using
      the wound-healing and transwell assays. Association of NEDD4 with activated EGFR
      was assayed by co-immunoprecipitation. Co-expression of NEDD4 with EGFR or PTEN
      was determined by immunohistochemical (IHC) staining in 63 lung adenocarcinoma
      tissue samples. Effects of NEDD4 ectopic expression or knockdown on PTEN
      ubiquitination and down-regulation, AKT activation and lysosomal secretion were
      examined using the GST-Uba pulldown assay, immunoblotting, immunofluorescent
      staining and a human cathepsin B ELISA assay respectively. The specific cathepsin
      B inhibitor CA-074Me was used for assessing the role of cathepsin B in lung
      cancer cell migration. RESULTS: Knockdown of NEDD4 significantly reduced EGF
      stimulated cell migration in non-small cell lung carcinoma (NSCLC) cells. Co
      immunoprecipitation assay found that NEDD4 is associated with EGFR complex upon
      EGF stimulation, and IHC staining indicates that NEDD4 is co-expressed with EGFR
      in lung adenocarcinoma tumor tissues, suggesting that NEDD4 might mediate lung
      cancer cell migration by interaction with the EGFR signaling complex.
      Interestingly, NEDD4 promotes the EGF-induced cathepsin B secretion, possibly
      through lysosomal exocytosis, as overexpression of the ligase-dead mutant of
      NEDD4 impedes lysosomal secretion, and knockdown of NEDD4 significantly reduced
      extracellular amount of cathepsin B induced by EGF. Consistent with the role of
      NEDD4, cathepsin B is pivotal for both basal and the EGF-stimulated lung cancer
      cell migration. Our studies propose a novel mechanism underlying the EGFR
      promoted lung cancer cell migration that is mediated by NEDD4 through regulation
      of cathepsin B secretion. CONCLUSION: NEDD4 mediates the EGFR lung cancer cell
      migration signaling through promoting lysosomal secretion of cathepsin B.

PMID- 29455657
TI  - Role of the HGF/c-MET tyrosine kinase inhibitors in metastasic melanoma.
AB  - Metastatic disease in a cancer patient still remains a therapeutic challenge.
      Metastatic process involves many steps, during which malignant cells succeed to
      activate cellular pathways promoting survival in hostile environment, engraftment
      and growth at the distant site from the primary tumor. Melanoma is known for its
      high propensity to produce metastases even at the early stages of the disease.
      Here we summarize the most important molecular mechanisms which were associated
      with the melanoma metastasis. Then, we specifically focus on the signaling
      pathway mediated by hepatocyte growth factor (HGF) and its receptor c-Met, which
      play an important role during physiological processes and were been associated
      with tumorigenesis. We also focus on the effect of the small molecule inhibitors
      of the tyrosine kinase domain of the c-Met receptor and its effects on properties
      of melanoma cell. We summarize recent studies, which involved inhibition of the
      HGF/c-Met signaling in order to decrease melanoma growth and metastatic capacity.

PMID- 29455658
TI  - Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic
      implications and challenges.
AB  - Breast cancer is a multifactorial disease and driven by aberrant regulation of
      cell signaling pathways due to the acquisition of genetic and epigenetic changes.
      An array of growth factors and their receptors is involved in cancer development
      and metastasis. Receptor Tyrosine Kinases (RTKs) constitute a class of receptors
      that play important role in cancer progression. RTKs are cell surface receptors
      with specialized structural and biological features which respond to
      environmental cues by initiating appropriate signaling cascades in tumor cells.
      RTKs are known to regulate various downstream signaling pathways such as MAPK,
      PI3K/Akt and JAK/STAT. These pathways have a pivotal role in the regulation of
      cancer stemness, angiogenesis and metastasis. These pathways are also imperative
      for a reciprocal interaction of tumor and stromal cells. Multi-faceted role of
      RTKs renders them amenable to therapy in breast cancer. However, structural
      mutations, gene amplification and alternate pathway activation pose challenges to
      anti-RTK therapy.

PMID- 29455659
TI  - Receptor tyrosine kinases and downstream pathways as druggable targets for cancer
      treatment: the current arsenal of inhibitors.
AB  - Searching for targets that allow pharmacological inhibition of cell proliferation
      in over-proliferative states, such as cancer, leads us to finely understand the
      complex mechanisms orchestrating the perfect control of mitosis number, frequency
      and pace as well as the molecular arrangements that induce cells to enter
      functional quiescence and brings them back to cycling in specific conditions.
      Although the mechanisms regulating cell proliferation have been described several
      years ago, never before has so much light been shed over this machinery as during
      the last decade when therapy targets have been explored and molecules, either
      synthetic or in the form of antibodies with the potential of becoming cancer
      drugs were produced and adjusted for specific binding and function. Proteins
      containing tyrosine kinase domains, either membrane receptors or cytoplasmic
      molecules, plus the ones activated by those in downstream pathways, having
      tyrosine kinase domains or not, such as RAS which is a GTPase and
      serine/threonine kinases such as RAF, play crucial role in conducting
      proliferation information from cell surroundings to the nucleus where gene
      expression takes place. Tyrosine kinases phosphorylate tyrosine residues in an
      activating mode and are found in important growth factor receptors, such as for
      ligands from families collectively known as VEGF, PDGF and EGF, to name a few and
      in intracellular downstream molecules. They all play important roles in normal
      physiology and are commonly found mutated or overexpressed in neoplastic states.
      Our objective here is to present such kinases as druggable targets for cancer
      therapy, highlighting the ones for which the pharmacological arsenal is
      available, discussing specificity, resistance mechanisms and treatment
      alternatives in cases of resistance, plus listing potential targets that have not
      been successfully worked yet.

PMID- 29455660
TI  - The relevance of tyrosine kinase inhibitors for global metabolic pathways in
      cancer.
AB  - Tumor metabolism is a thrilling discipline that focuses on mechanisms used by
      cancer cells to earn crucial building blocks and energy to preserve growth and
      overcome resistance to various treatment modalities. At the same time, therapies
      directed specifically against aberrant signalling pathways driven by protein
      tyrosine kinases (TKs) involved in proliferation, metastasis and growth count for
      several years to promising anti-cancer approaches. In this respect, small
      molecule inhibitors are the most widely used clinically relevant means for
      targeted therapy, with a rising number of approvals for TKs inhibitors. In this
      review, we discuss recent observations related to TKs-associated metabolism and
      to metabolic feedback that is initialized as cellular response to particular TK
      targeted therapies. These observations provide collective evidence that
      therapeutic responses are primarily linked to such pathways as regulation of
      lipid and amino acid metabolism, TCA cycle and glycolysis, advocating therefore
      the development of further effective targeted therapies against a broader
      spectrum of TKs to treat patients whose tumors display deregulated signalling
      driven by these proteins.

PMID- 29455661
TI  - Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor
      as a novel anticancer agent with minimal toxicity.
AB  - BACKGROUND: Both the type I insulin-like growth factor receptor (IGF1R) and Src
      pathways are associated with the development and progression of numerous types of
      human cancer, and Src activation confers resistance to anti-IGF1R therapies.
      Hence, targeting both IGF1R and Src concurrently is one of the main challenges in
      combating resistance to the currently available anti-IGF1R-based anticancer
      therapies. However, the enhanced toxicity from this combinatorial treatment could
      be one of the main hurdles for this strategy, suggesting the necessity of
      developing a novel strategy for co-targeting IGF1R and Src to meet an urgent
      clinical need. METHODS: We synthesized a series of 4-aminopyrazolo[3,4
      d]pyrimidine-based dual IGF1R/Src inhibitors, selected LL28 as an active compound
      and evaluated its potential antitumor effects in vitro and in vivo using the MTT
      assay, colony formation assays, flow cytometric analysis, a tumor xenograft
      model, and the Kras G12D/+ -driven spontaneous lung tumorigenesis model. RESULTS:
      LL28 markedly suppressed the activation of IGF1R and Src and significantly
      inhibited the viability of several NSCLC cell lines in vitro by inducing
      apoptosis. Administration of mice with LL28 significantly suppressed the growth
      of H1299 NSCLC xenograft tumors without overt toxicity and substantially reduced
      the multiplicity, volume, and load of lung tumors in the Kras G12D/+ -driven lung
      tumorigenesis model. CONCLUSIONS: The present results suggest the potential of
      LL28 as a novel anticancer drug candidate targeting both IGF1R and Src, providing
      a new avenue to efficient anticancer therapies. Further investigation is
      warranted in advanced preclinical and clinical settings.

PMID- 29455662
TI  - The role of RICTOR downstream of receptor tyrosine kinase in cancers.
AB  - The importance of the network defined by phosphatidylinositol-3-kinase (PI3K),
      AKT and mammalian target of rapamycin (mTOR) downstream of Receptor Tyrosine
      Kinase (RTK) has been known for many years but the central role of RICTOR
      (rapamycin-insensitive companion of mTOR) in this pathway is only starting to
      emerge. RICTOR is critical for mTORC2 (the mammalian target of rapamycin complex
      2) kinase activity and as such plays a key role downstream of RTK. Alterations of
      RICTOR have been identified in a number of cancer cell types and its involvement
      in tumorigenesis has begun to be unraveled recently. Here, we summarize new
      research into the biology of RICTOR signaling in cancers focusing on tumors with
      altered RTK. We show that, as a key signaling node and critical effector of RTKs,
      RICTOR is becoming a valuable therapeutic target in cancer with altered RTK.

PMID- 29455663
TI  - Targeting tumour microenvironment by tyrosine kinase inhibitor.
AB  - Tumour microenvironment (TME) is a key determinant of tumour growth and
      metastasis. TME could be very different for each type and location of tumour and
      TME may change constantly during tumour growth. Multiple counterparts in
      surrounding microenvironment including mesenchymal-, hematopoietic-originated
      cells as well as non-cellular components affect TME. Thus, therapeutics that can
      disrupt the tumour-favouring microenvironment should be further explored for
      cancer therapy. Previous efforts in unravelling the dysregulated mechanisms of
      TME components has identified numerous protein tyrosine kinases, while its
      corresponding inhibitors have demonstrated potent modulatory effect on TME.
      Recent works have demonstrated that beyond the direct action on cancer cells,
      tyrosine kinase inhibitors (TKIs) have been implicated in inactivation or
      normalization of dysregulated TME components leading to cancer regression. Either
      through re-sensitizing the tumour cells or reversing the immunological tolerance
      microenvironment, the emergence of these TME modulatory mechanism of TKIs
      supports the combinatory use of TKIs with current chemotherapy or immunotherapy
      for cancer therapy. Therefore, an appropriate understanding on TME modulation by
      TKIs may offer another mode of action of TKIs for cancer treatment. This review
      highlights mode of kinase activation or paracrine ligand production from TME
      components and summarises the findings on the potential use of various TKIs on
      regulating TME components. At last, the combination use of current TKIs with
      immunotherapy in the perspectives of efficacy and safety are discussed.

PMID- 29455664
TI  - Advances in studies of tyrosine kinase inhibitors and their acquired resistance.
AB  - Protein tyrosine kinase (PTK) is one of the major signaling enzymes in the
      process of cell signal transduction, which catalyzes the transfer of ATP-gamma
      phosphate to the tyrosine residues of the substrate protein, making it
      phosphorylation, regulating cell growth, differentiation, death and a series of
      physiological and biochemical processes. Abnormal expression of PTK usually leads
      to cell proliferation disorders, and is closely related to tumor invasion,
      metastasis and tumor angiogenesis. At present, a variety of PTKs have been used
      as targets in the screening of anti-tumor drugs. Tyrosine kinase inhibitors
      (TKIs) compete with ATP for the ATP binding site of PTK and reduce tyrosine
      kinase phosphorylation, thereby inhibiting cancer cell proliferation. TKI has
      made great progress in the treatment of cancer, but the attendant acquired
      acquired resistance is still inevitable, restricting the treatment of cancer. In
      this paper, we summarize the role of PTK in cancer, TKI treatment of tumor
      pathways and TKI acquired resistance mechanisms, which provide some reference for
      further research on TKI treatment of tumors.

PMID- 29455665
TI  - PTEN/PTENP1: 'Regulating the regulator of RTK-dependent PI3K/Akt signalling', new
      targets for cancer therapy.
AB  - Regulation of the PI-3 kinase (PI3K)/Akt signalling pathway is essential for
      maintaining the integrity of fundamental cellular processes, cell growth,
      survival, death and metabolism, and dysregulation of this pathway is implicated
      in the development and progression of cancers. Receptor tyrosine kinases (RTKs)
      are major upstream regulators of PI3K/Akt signalling. The phosphatase and tensin
      homologue (PTEN), a well characterised tumour suppressor, is a prime antagonist
      of PI3K and therefore a negative regulator of this pathway. Loss or inactivation
      of PTEN, which occurs in many tumour types, leads to overactivation of
      RTK/PI3K/Akt signalling driving tumourigenesis. Cellular PTEN levels are tightly
      regulated by a number of transcriptional, post-transcriptional and post
      translational regulatory mechanisms. Of particular interest, transcription of the
      PTEN pseudogene, PTENP1, produces sense and antisense transcripts that exhibit
      post-transcriptional and transcriptional modulation of PTEN expression
      respectively. These additional levels of regulatory complexity governing PTEN
      expression add to the overall intricacies of the regulation of RTK/PI-3 K/Akt
      signalling. This review will discuss the regulation of oncogenic PI3K signalling
      by PTEN (the regulator) with a focus on the modulatory effects of the sense and
      antisense transcripts of PTENP1 on PTEN expression, and will further explore the
      potential for new therapeutic opportunities in cancer treatment.

PMID- 29455666
TI  - KRAS oncogene in non-small cell lung cancer: clinical perspectives on the
      treatment of an old target.
AB  - Lung neoplasms are the leading cause of death by cancer worldwide. Non-small cell
      lung cancer (NSCLC) constitutes more than 80% of all lung malignancies and the
      majority of patients present advanced disease at onset. However, in the last
      decade, multiple oncogenic driver alterations have been discovered and each of
      them represents a potential therapeutic target. Although KRAS mutations are the
      most frequently oncogene aberrations in lung adenocarcinoma patients, effective
      therapies targeting KRAS have yet to be developed. Moreover, the role of KRAS
      oncogene in NSCLC remains unclear and its predictive and prognostic impact
      remains controversial. The study of the underlying biology of KRAS in NSCLC
      patients could help to determine potential candidates to evaluate novel targeted
      agents and combinations that may allow a tailored treatment for these patients.
      The aim of this review is to update the current knowledge about KRAS-mutated lung
      adenocarcinoma, including a historical overview, the biology of the molecular
      pathways involved, the clinical relevance of KRAS mutations as a prognostic and
      predictive marker and the potential therapeutic approaches for a personalized
      treatment of KRAS-mutated NSCLC patients.

PMID- 29455668
TI  - Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated
      therapeutic opportunities.
AB  - c-Met is a receptor tyrosine kinase belonging to the MET (MNNG HOS transforming
      gene) family, and is expressed on the surfaces of various cells. Hepatocyte
      growth factor (HGF) is the ligand for this receptor. The binding of HGF to c-Met
      initiates a series of intracellular signals that mediate embryogenesis and wound
      healing in normal cells. However, in cancer cells, aberrant HGF/c-Met axis
      activation, which is closely related to c-Met gene mutations, overexpression, and
      amplification, promotes tumor development and progression by stimulating the
      PI3K/AKT, Ras/MAPK, JAK/STAT, SRC, Wnt/beta-catenin, and other signaling
      pathways. Thus, c-Met and its associated signaling pathways are clinically
      important therapeutic targets. In this review, we elaborate on the molecular
      structure of c-Met and HGF and the mechanism through which their interaction
      activates the PI3K/AKT, Ras/MAPK, and Wnt signaling pathways. We also summarize
      the connection between c-Met and RON and EGFR, which are also receptor tyrosine
      kinases. Finally, we introduce the current therapeutic drugs that target c-Met in
      primary tumors, and their use in clinical research.

PMID- 29455667
TI  - Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its
      Targeting by Natural Products.
AB  - Tyrosine kinases belong to a family of enzymes that mediate the movement of the
      phosphate group to tyrosine residues of target protein, thus transmitting signals
      from the cell surface to cytoplasmic proteins and the nucleus to regulate
      physiological processes. Non-receptor tyrosine kinases (NRTK) are a sub-group of
      tyrosine kinases, which can relay intracellular signals originating from
      extracellular receptor. NRTKs can regulate a huge array of cellular functions
      such as cell survival, division/propagation and adhesion, gene expression, immune
      response, etc. NRTKs exhibit considerable variability in their structural make
      up, having a shared kinase domain and commonly possessing many other domains such
      as SH2, SH3 which are protein-protein interacting domains. Recent studies show
      that NRTKs are mutated in several hematological malignancies, including
      lymphomas, leukemias and myelomas, leading to aberrant activation. It can be due
      to point mutations which are intragenic changes or by fusion of genes leading to
      chromosome translocation. Mutations that lead to constitutive kinase activity
      result in the formation of oncogenes, such as Abl, Fes, Src, etc. Therefore,
      specific kinase inhibitors have been sought after to target mutated kinases. A
      number of compounds have since been discovered, which have shown to inhibit the
      activity of NRTKs, which are remarkably well tolerated. This review covers the
      role of various NRTKs in the development of hematological cancers, including
      their deregulation, genetic alterations, aberrant activation and associated
      mutations. In addition, it also looks at the recent advances in the development
      of novel natural compounds that can target NRTKs and perhaps in combination with
      other forms of therapy can show great promise for the treatment of hematological
      malignancies.

PMID- 29455669
TI  - EGFR-TKIs resistance via EGFR-independent signaling pathways.
AB  - Tyrosine kinase inhibitors (TKIs)-treatments bring significant benefit for
      patients harboring epidermal growth factor receptor (EGFR) mutations, especially
      for those with lung cancer. Unfortunately, the majority of these patients
      ultimately develop to the acquired resistance after a period of treatment. Two
      central mechanisms are involved in the resistant process: EGFR secondary
      mutations and bypass signaling activations. In an EGFR-dependent manner, acquired
      mutations, such as T790 M, interferes the interaction between TKIs and the kinase
      domain of EGFR. While in an EGFR-independent manner, dysregulation of other
      receptor tyrosine kinases (RTKs) or abnormal activation of downstream compounds
      both have compensatory functions against the inhibition of EGFR through
      triggering phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein
      kinase (MAPK) signaling axes. Nowadays, many clinical trials aiming to overcome
      and prevent TKIs resistance in various cancers are ongoing or completed. EGFR
      TKIs in accompany with the targeted agents for resistance-related factors afford
      a promising first-line strategy to further clinical application.

PMID- 29455670
TI  - The rationale for druggability of CCDC6-tyrosine kinase fusions in lung cancer.
AB  - Gene fusions occur in up to 17% of solid tumours. Oncogenic kinases are often
      involved in such fusions. In lung cancer, almost 30% of patients carrying an
      activated oncogene show the fusion of a tyrosine kinase to an heterologous gene.
      Several genes are partner in the fusion with the three kinases ALK, ROS1 and RET
      in lung. The impaired function of the partner gene, in combination with the
      activation of the kinase, may alter the cell signaling and promote the cancer
      cell addiction to the oncogene. Moreover, the gene that is partner in the fusion
      to the kinase may affect the response to therapeutics and/or promote resistance
      in the cancer cells. Few genes are recurrent partners in tyrosine kinase fusions
      in lung cancer, including CCDC6, a recurrent partner in ROS1 and RET fusions,
      that can be selected as possible target for new strategies of combined therapy
      including TKi.

PMID- 29455671
TI  - Oncogenic fusion proteins adopt the insulin-like growth factor signaling pathway.
AB  - The insulin-like growth factor-1 receptor (IGF1R) has been identified as a potent
      anti-apoptotic, pro-survival tyrosine kinase-containing receptor. Overexpression
      of the IGF1R gene constitutes a typical feature of most human cancers. Consistent
      with these biological roles, cells expressing high levels of IGF1R are expected
      not to die, a quintessential feature of cancer cells. Tumor specific chromosomal
      translocations that disrupt the architecture of transcription factors are a
      common theme in carcinogenesis. Increasing evidence gathered over the past
      fifteen years demonstrate that this type of genomic rearrangements is common not
      only among pediatric and hematological malignancies, as classically thought, but
      may also provide a molecular and cytogenetic foundation for an ever-increasing
      portion of adult epithelial tumors. In this review article we provide evidence
      that the mechanism of action of oncogenic fusion proteins associated with both
      pediatric and adult malignancies involves transactivation of the IGF1R gene, with
      ensuing increases in IGF1R levels and ligand-mediated receptor phosphorylation.
      Disrupted transcription factors adopt the IGF1R signaling pathway and elicit
      their oncogenic activities via activation of this critical regulatory network.
      Combined targeting of oncogenic fusion proteins along with the IGF1R may
      constitute a promising therapeutic approach.

PMID- 29455672
TI  - Non ABL-directed inhibitors as alternative treatment strategies for chronic
      myeloid leukemia.
AB  - The introduction of ABL Tyrosine Kinase Inhibitors (TKIs) has significantly
      improved the outcome of Chronic Myeloid Leukemia (CML) patients that, in large
      part, achieve satisfactory hematological, cytogenetic and molecular remissions.
      However, approximately 15-20% fail to obtain optimal responses according to the
      current European Leukemia Network recommendation because of drug intolerance or
      resistance.Moreover, a plethora of evidence suggests that Leukemic Stem Cells
      (LSCs) show BCR-ABL1-independent survival. Hence, they are unresponsive to TKIs,
      leading to disease relapse if pharmacological treatment is discontinued.All
      together, these biological events generate a subpopulation of CML patients in
      need of alternative therapeutic strategies to overcome TKI resistance or to
      eradicate LSCs in order to allow cure of the disease.In this review we update the
      role of "non ABL-directed inhibitors" targeting signaling pathways downstream of
      the BCR-ABL1 oncoprotein and describe immunological approaches activating
      specific T cell responses against CML cells.

PMID- 29455674
TI  - Aggressive fibromatosis in the infratemporal fossa presenting as trismus: a case
      report.
AB  - BACKGROUND: Here we report a very rare entity of an infratemporal region
      aggressive fibromatosis in a 23-year-old Tharu man who had presented with the
      symptoms of painless but progressive trismus. CASE PRESENTATION: We describe a
      case of aggressive fibromatosis in a 23-year-old Tharu man. Radiological imaging
      as well as an immunohistochemistry panel from a biopsy indicated a diagnosis of
      an aggressive fibromatosis. Since there was no aggravation in his trismus
      following surgery and because of his poor socioeconomic status, he was advised to
      attend regular follow-up visits without any adjuvant therapy. CONCLUSIONS: This
      case report adds to the notion of keeping the differential diagnosis of an
      aggressive fibromatosis in all patients presenting with progressive but painless
      trismus. The characteristic imaging findings as well an immunohistochemistry
      panel will help us clinch the correct diagnosis.

PMID- 29455676
TI  - Evaluation of an Ophthalmoscopy Simulator to Teach Funduscopy Skills to Pediatric
      Residents.
AB  - BACKGROUND: Medical school and residency training in ophthalmoscopic evaluation
      is limited, reducing diagnostic accuracy. We sought to evaluate the efficacy of
      self-study using an ophthalmoscopy simulator to improve the technical motor
      skills involved in direct funduscopy in postgraduate pediatric residents.
      METHODS: In this randomized-controlled study, 17 pediatric residents
      (postgraduate years 1-3) were randomized to control (n=8) or intervention (n=9)
      groups. Participants were asked to correctly identify the funduscopic findings
      presented to them on an ophthalmoscopy simulator after being trained on its use.
      Each participant was asked to review 20 images of the fundus, and then record
      their multiple-choice response on a scantron sheet listing all possible
      funduscopic pathologies. Pre- and post-intervention testing was performed. Survey
      data assessing exposure to funduscopy skills during undergraduate and
      postgraduate training and overall experience with the simulator were collected.
      RESULTS: Most (65% [11/17]) participants reported minimal or no formal teaching
      in ophthalmology during their undergraduate medical studies. Average pre
      intervention score (of 20) was 10.24+/-1.75 (51%) for the entire group, with no
      statistically significant difference between average pre-score in the control
      (10.63+/-1.77) versus intervention (9.89+/-1.76, p=0.405) groups. Intervention
      subjects experienced a statistically significant improvement in scores (9.89+/
      1.76 vs. 12.78+/-2.05, p=0.006 [95% confidence interval 4.80-0.98]), but control
      subjects did not. CONCLUSIONS: A single session with an ophthalmoscopy simulator
      can improve diagnostic accuracy in postgraduate pediatric trainees. Use of
      ophthalmoscopy simulation represents a novel addition to traditional learning
      methods for postgraduate pediatric residents that can help trainees to improve
      their confidence and accuracy in performing this challenging examination.

PMID- 29455678
TI  - Cryptic species and their utilization of indigenous and non-indigenous
      intermediate hosts in the acanthocephalan Polymorphus minutus sensu lato
      (Polymorphidae).
AB  - The bird-infecting acanthocephalan Polymorphus minutus has been suggested to
      comprise different lineages or even cryptic species using different intermediate
      hosts. To clarify this open question, we investigated Polymorphus cf. minutus
      cystacanths originating from amphipod intermediate hosts from 27 sites in Germany
      and France. Parasites and hosts were identified using integrated datasets (COI
      and/or morphology for hosts and COI + ITS1-5.8S-ITS2 for parasites).Mitochondrial
      and nuclear data (ITS1) strongly support the existence of three cryptic species
      in Polymorphus cf. minutus (type 1-3). These three types reveal a high degree of
      intermediate host specificity, with Polymorphus type 1 only encountered in
      Gammarus fossarum type B, Polymorphus type 2 in Echinogammarus sp. and
      Echinogammarus berilloni, and Polymorphus type 3 in Gammarus pulex and Gammarus
      roeselii. Our results point to a so far neglected cryptic diversity of the genus
      Polymorphus in Central Europe. Furthermore, Polymorphus type 2 is most likely a
      non-native parasite in Germany that co-invaded with E. berilloni from the
      Mediterranean area. Potentially, type 3 originates from South-East Europe and
      migrated to Germany by G. roeselii, where it might have captured G. pulex as an
      intermediate host. Therefore, our findings can be seen in the context of
      ecological globalization in terms of the anthropogenic displacement of
      intermediate hosts and its impact on the genetic divergence of the parasites.

PMID- 29455675
TI  - The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non
      small cell lung cancer (NSCLC).
AB  - Lung cancer is the leading cause of death by cancer in North America. A decade
      ago, genomic rearrangements in the anaplastic lymphoma kinase (ALK) receptor
      tyrosine kinase were identified in a subset of non-small cell lung carcinoma
      (NSCLC) patients. Soon after, crizotinib, a small molecule ATP-competitive ALK
      inhibitor was proven to be more effective than chemotherapy in ALK-positive NSCLC
      patients. Crizotinib and two other ATP-competitive ALK inhibitors, ceritinib and
      alectinib, are approved for use as a first-line therapy in these patients, where
      ALK rearrangement is currently diagnosed by immunohistochemistry and in situ
      hybridization. The clinical success of these three ALK inhibitors has led to the
      development of next-generation ALK inhibitors with even greater potency and
      selectivity. However, patients inevitably develop resistance to ALK inhibitors
      leading to tumor relapse that commonly manifests in the form of brain metastasis.
      Several new approaches aim to overcome the various mechanisms of resistance that
      develop in ALK-positive NSCLC including the knowledge-based alternate and
      successive use of different ALK inhibitors, as well as combined therapies
      targeting ALK plus alternative signaling pathways. Key issues to resolve for the
      optimal implementation of established and emerging treatment modalities for ALK
      rearranged NSCLC therapy include the high cost of the targeted inhibitors and the
      potential of exacerbated toxicities with combination therapies.

PMID- 29455677
TI  - The gene-environmental architecture of the development of adolescent substance
      use.
AB  - BACKGROUND: Using a longitudinal twin design and a latent growth
      curve/autoregressive approach, this study examined the genetic-environmental
      architecture of substance use across adolescence. METHODS: Self-reports of
      substance use (i.e. alcohol, marijuana) were collected at ages 13, 14, 15, and 17
      years from 476 twin pairs (475 boys, 477 girls) living in the Province of Quebec,
      Canada. Substance use increased linearly across the adolescent years. RESULTS:
      ACE modeling revealed that genetic, as well as shared and non-shared
      environmental factors explained the overall level of substance use and that these
      same factors also partly accounted for growth in substance use from age 13 to 17.
      Additional genetic factors predicted the growth in substance use. Finally,
      autoregressive effects revealed age-specific non-shared environmental influences
      and, to a lesser degree, age-specific genetic influences, which together
      accounted for the stability of substance use across adolescence. CONCLUSIONS: The
      results support and expand the notion that genetic and environmental influences
      on substance use during adolescence are both developmentally stable and
      developmentally dynamic.

PMID- 29455679
TI  - Nutrient profiling and adherence to components of the UK national dietary
      guidelines association with metabolic risk factors for CVD and diabetes: Airwave
      Health Monitoring Study.
AB  - CVD is the leading cause of death worldwide. Diet is a key modifiable component
      in the development of CVD. No official UK diet quality index exists for use in UK
      nutritional epidemiological studies. The aims of this study are to: (i) develop a
      diet quality index based on components of UK dietary reference values (DRV) and
      (ii) determine the association between the index, the existing UK nutrient
      profile (NP) model and a comprehensive range of cardiometabolic risk markers
      among a British adult population. A cross-sectional analysis was conducted using
      data from the Airwave Health Monitoring Study (n 5848). Dietary intake was
      measured by 7-d food diary and metabolic risk using waist circumference, BMI,
      blood lipid profile, glycated Hb (HbA1c) and blood pressure measurements. Diet
      quality was assessed using the novel DRV index and NP model. Associations between
      diet and cardiometabolic risk were analysed via multivariate linear models and
      logistic regression. A two-point increase in NP score was associated with total
      cholesterol (beta -0.33 mmol/l, P<0.0001) and HbA1c (beta -0.01 %, P<0.0001). A
      two-point increase in DRV score was associated with waist circumference (beta 
      0.56 cm, P<0.0001), BMI (beta -0.15 kg/m2, P<0.0001), total cholesterol (beta 
      0.06 mmol/l, P<0.0001) and HbA1c (beta -0.02 %, P=0.002). A one-point increase in
      DRV score was associated with type 2 diabetes (T2D) (OR 0.94, P=0.01) and obesity
      (OR 0.95, P<0.0001). The DRV index is associated with overall diet quality and
      risk factors for CVD and T2D, supporting its application in nutritional
      epidemiological studies investigating CVD risk in a UK population.

PMID- 29455680
TI  - Emergency Medical Service (EMS) Utilization by Syrian Refugees Residing in
      Ankara, Turkey.
AB  - : Introduction Many Syrians have left their country and migrated to other
      countries since March 2011, due to the civil war. As of March 2016, a total of
      2,747,946 Syrian refugees had immigrated to Turkey. Some Syrian refugees have
      been living in camps, while 2,475,134 have been living in metropolitan areas,
      such as Ankara. Study Objective This study investigated Emergency Medical Service
      (EMS) utilization among Syrian refugees residing in Ankara. METHODS: This study
      was a descriptive, cross-sectional database analysis using data obtained from the
      Department of EMS of the Ankara Provincial Health Directorate. CONCLUSION: Five
      stations in the Altindag region of Ankara responded to 42% of all calls from
      Syrian refugees. Prehospital EMS in Ankara have been used mostly by Syrian
      refugees younger than 18-years-old. Study findings also suggest that medical
      staff in regions where Syrian refugees are likely to be treated should be
      supported and provided with the ability to overcome language barriers and
      cultural differences. Altiner AO , Tekeli Yesil S . Emergency Medical Service
      (EMS) utilization by Syrian refugees residing in Ankara, Turkey. Prehosp Disaster
      Med. 2018;33(2):160-164.

PMID- 29455681
TI  - Human dendritic cell sequestration onto the Necator americanus larval sheath
      during ex-sheathing: a possible mechanism for immune privilege.
AB  - Despite the profound health implications of Necator americanus infection in
      humans, many aspects of its interaction with the host immune system are poorly
      understood. Here we investigated the early events at the interface of N.
      americanus larvae (L3) and human dendritic cells (DCs). Our data show that co
      culturing DCs and the larvae trigger ex-sheathing of hookworms rapidly where a
      majority of DCs are sequestered onto the larval sheath allowing the ex-sheathed
      larvae to migrate away unchallenged. Intriguingly, DCs show negligible
      interaction with the ex-sheathed larvae, alluding to differences between the
      surface chemistry of the larva and its sheath. Furthermore, blocking of two key C
      type lectin receptors on DC surface (i.e. DC-SIGN and mannose receptor) resulted
      in inhibition of ex-sheathing process and DC sequestration, highlighting the
      importance of C-type lectins on DCs in the induction of the ex-sheathing.
      Analyses of DC phenotype and cytokine profile after co-culture with the N.
      americanus larvae showed an immature phenotype as evidenced by the low expression
      of the maturation markers and cytokines. These data provide new insights into
      early events at the interface of human DCs and N. americanus larvae and could
      explain how L3 evade immune recognition upon initial interaction with DCs.

PMID- 29455682
TI  - Characterization of Interventional Studies of the Cholera Epidemic in Haiti.
AB  - In October 2010, the Haitian Ministry of Public Health and Population (MSPP; Port
      au Prince, Haiti) reported a cholera epidemic caused by contamination of the
      Artibonite River by a United Nation Stabilization Mission camp. Interventional
      studies of the subsequent responses, including a descriptive Methods section and
      systematic approach, may be useful in facilitating comparisons and applying
      lessons learned to future outbreaks. The purpose of this study was to examine
      publicly available documents relating to the 2010 cholera outbreak to answer: (1)
      What information is publicly available on interventional studies conducted during
      the epidemic, and what was/were the impact(s)? and (2) Can the interventions be
      compared, and what lessons can be learned from their comparison? A PubMed
      (National Center for Biotechnology Information, National Institutes of Health;
      Bethesda, Maryland USA) search was conducted using the parameters "Haiti" and
      "cholera." Studies were categorized as "interventional research,"
      "epidemiological research," or "other." A distinction was made between studies
      and narrative reports. The PubMed search yielded 171 papers, 59 (34.0%) of which
      were epidemiological and 12 (7.0%) were interventional studies. The remaining 100
      papers (59.0%) comprised largely of narrative, anecdotal descriptions. An
      expanded examination of publications by the World Health Organization (WHO;
      Geneva, Switzerland), the Center for Research in the Epidemiology of Disasters
      (CRED; Brussels, Belgium), United States Agency for International Development
      (USAID; Washington, DC USA)-Development Experience Clearinghouse (DEC), and US
      National Library of Medicine's (NLM; Bethesda, Maryland USA) Disaster Literature
      databases yielded no additional interventional studies. The unstructured formats
      and differing levels of detail prohibited comparisons between interventions, even
      between those with a similar approach. Only two (17.0%) interventional studies
      included any impact data, although neither commented whether the intervention
      improved health or reduced incidence or mortality related to cholera. Agreed
      frameworks for guiding responses and subsequent reporting are needed to ensure
      reports contain sufficient detail to draw conclusions for the definition of best
      practices and for the design of future interventions. Miller J , Birnbaum ML .
      Characterization of interventional studies of the cholera epidemic in Haiti.
      Prehosp Disaster Med. 2018;33(2):176-181.

PMID- 29455673
TI  - Kinase-targeted cancer therapies: progress, challenges and future directions.
AB  - The human genome encodes 538 protein kinases that transfer a gamma-phosphate
      group from ATP to serine, threonine, or tyrosine residues. Many of these kinases
      are associated with human cancer initiation and progression. The recent
      development of small-molecule kinase inhibitors for the treatment of diverse
      types of cancer has proven successful in clinical therapy. Significantly, protein
      kinases are the second most targeted group of drug targets, after the G-protein
      coupled receptors. Since the development of the first protein kinase inhibitor,
      in the early 1980s, 37 kinase inhibitors have received FDA approval for treatment
      of malignancies such as breast and lung cancer. Furthermore, about 150 kinase
      targeted drugs are in clinical phase trials, and many kinase-specific inhibitors
      are in the preclinical stage of drug development. Nevertheless, many factors
      confound the clinical efficacy of these molecules. Specific tumor genetics, tumor
      microenvironment, drug resistance, and pharmacogenomics determine how useful a
      compound will be in the treatment of a given cancer. This review provides an
      overview of kinase-targeted drug discovery and development in relation to
      oncology and highlights the challenges and future potential for kinase-targeted
      cancer therapies.

PMID- 29455683
TI  - Defining CT Perfusion Thresholds for Infarction in the Golden Hour and With Ultra
      Early Reperfusion.
AB  - In this brief report, computed tomography perfusion (CTP) thresholds predicting
      follow-up infarction in patients presenting 20 to 23 seconds and cerebral blood
      flow <5 to 7 ml/min-1/(100 g)-1 or relative cerebral blood flow <0.14 to 0.20
      optimally predicted the final infarct. These thresholds are stricter than
      published thresholds.

PMID- 29455684
TI  - OPTIMIZING USABILITY OF AN ECONOMIC DECISION SUPPORT TOOL: PROTOTYPE OF THE
      EQUIPT TOOL.
AB  - OBJECTIVES: Economic decision-support tools can provide valuable information for
      tobacco control stakeholders, but their usability may impact the adoption of such
      tools. This study aims to illustrate a mixed-method usability evaluation of an
      economic decision-support tool for tobacco control, using the EQUIPT ROI tool
      prototype as a case study. METHODS: A cross-sectional mixed methods design was
      used, including a heuristic evaluation, a thinking aloud approach, and a
      questionnaire testing and exploring the usability of the Return of Investment
      tool. RESULTS: A total of sixty-six users evaluated the tool (thinking aloud) and
      completed the questionnaire. For the heuristic evaluation, four experts evaluated
      the interface. In total twenty-one percent of the respondents perceived good
      usability. A total of 118 usability problems were identified, from which twenty
      six problems were categorized as most severe, indicating high priority to fix
      them before implementation. CONCLUSIONS: Combining user-based and expert-based
      evaluation methods is recommended as these were shown to identify unique
      usability problems. The evaluation provides input to optimize usability of a
      decision-support tool, and may serve as a vantage point for other developers to
      conduct usability evaluations to refine similar tools before wide-scale
      implementation. Such studies could reduce implementation gaps by optimizing
      usability, enhancing in turn the research impact of such interventions.

PMID- 29455685
TI  - HEALTH TECHNOLOGY ASSESSMENT EVIDENCE ON E-HEALTH/M-HEALTH TECHNOLOGIES:
      EVALUATING THE TRANSPARENCY AND THOROUGHNESS.
AB  - OBJECTIVES: Evaluation is crucial for integration of e-Health/m-Health into
      healthcare systems and health technology assessment (HTA) could offer sound
      methodological basis for these evaluations. Aim of this study was to look for HTA
      reports on e-Health/m-Health technologies and to analyze their transparency,
      consistency and thoroughness, with the goal to detect areas that need
      improvement. METHODS: PubMed, ISI-WOS, and University of York - Centre for
      Reviews and Dissemination-electronic databases were searched to identify reports
      on e-Health/m-Health technologies, published up until April 1, 2016. The
      International Network of Agencies for Health Technology Assessment (INAHTA)
      checklist was used to evaluate transparency and consistency of included reports.
      Thoroughness was assessed by checking the presence of domains suggested by the
      European network for Health Technology Assessment (EUnetHTA) HTA Core Model.
      RESULTS: Twenty-eight reports published between 1999 and 2015 were included. Most
      were delivered by non-European countries (71.4 percent) and only 35.7 percent
      were classified as full reports. All the HTA reports defined the scope of
      research whereas more than 80 percent provided author details, summary, discussed
      findings, and conclusion. On the contrary, policy and research questions were
      clearly defined in around 30 percent and 50 percent of reports. With respect to
      the EUnetHTA Core Model, around 70 percent of reports dealt with effectiveness
      and economic evaluation, more than 50 percent described health problem and
      approximately 40 percent organizational and social aspects. CONCLUSIONS: E
      Health/m-Health technologies are increasingly present in the field of HTA. Yet,
      our review identified several missing elements. Most of the reports failed to
      respond to relevant assessment components, especially ethical, social and
      organizational implications.

PMID- 29455686
TI  - COST-UTILITY ANALYSIS OF PRIVATE CONTRACTING TO REDUCE PUBLIC WAITING TIMES FOR
      JOINT REPLACEMENT SURGERY.
AB  - OBJECTIVES: Earlier treatment of publicly funded patients may achieve health
      gains that justify the additional costs of reducing waiting times. This study
      reports on the cost-effectiveness of implementing a private contracting model to
      meet alternative maximum waiting time targets for publicly funded patients
      undergoing total knee replacement surgery in Australia. METHODS: A linked
      decision tree and cohort Markov model was developed and populated and validated
      using secondary data sources to represent the pathways, costs, and quality
      adjusted life-years (QALYs) gained of non-urgent patients with alternative
      waiting times for total knee replacement surgery to a maximum age of 100 years.
      RESULTS: Assuming public waiting times are reduced through the purchase of
      private services, additional QALYs are gained at an incremental cost of less than
      $40,000. Value could be increased if lower private prices could be negotiated.
      Results are also sensitive to the rate of deterioration in function while waiting
      for surgery and the impact of functional status at the time of surgery on
      postsurgery outcomes. CONCLUSIONS: More evidence on the value of expanded
      capacity or new models of care may inform new funding models to support such
      investments and reduced prices for new technologies, leading to more efficient
      and sustainable publicly funded healthcare systems.

PMID- 29455687
TI  - Distinct risk factors for obsessive and compulsive symptoms in chronic
      schizophrenia.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is common in clozapine-treated
      patients although the actual prevalence, phenomenology and risk factors remain
      unclear. The aim of the present study was to address the three aforementioned
      questions. METHODS: The electronic records of a large cohort of clozapine
      medicated schizophrenia patients routinely screened for OCD were used. The
      Obsessive Compulsive Inventory Revised version (OCI-R) was available from 118
      cases and a 21 points cut-off threshold for OCD was defined. RESULTS: OCD
      prevalence was 47%, higher in patients on poly-pharmacy than on monotherapy (64%
      vs 31%; p = 0.001). Two OCI-R factors had significantly higher scores and
      distinct risk factors: checking behaviour (mean = 5.1; SD = 3.6) correlated with
      length of clozapine treatment (r = 0.21; p = 0.026), and obsessing factor (mean =
      4.8; SD = 3.6) correlated with psychosis severity (r = 0.59; p = 0.001). These
      factors along with total OCI-R, did not correlate with either clozapine dose or
      plasma levels, after correcting for psychosis severity. CONCLUSIONS: Screening
      for OCD in clozapine patients, and probably in those treated with structurally
      similar drugs with potent antiserotoninergic properties, should be widely adopted
      by clinicians. Further research is needed to understand the pathophysiology
      underlying repetitive behavior onset in clozapine-treated patients.

PMID- 29455688
TI  - Early-life nutritional status and metabolic syndrome: gender-specific
      associations from a cross-sectional analysis of the Brazilian Longitudinal Study
      of Adult Health (ELSA-Brasil).
AB  - OBJECTIVE: In the present study we investigated gender-specific associations of
      low birth weight (LBW) and shorter relative leg length with metabolic syndrome
      (MetS) after adjusting for sociodemographic characteristics and health-related
      behaviours. We also investigated whether these associations are independent of
      age at menarche and BMI at 20 years old. DESIGN: Cross-sectional analysis.
      SUBJECTS: Baseline data from 12 602 participants (35-74 years) of the Brazilian
      Longitudinal Study of Adult Health (ELSA-Brasil), 2008-2010. SETTING: MetS was
      defined according to the revised National Cholesterol Education Program Adult
      Treatment Panel III guidelines. LBW (<2.5 kg) and age- and sex-standardized
      relative leg length (high, medium and low) were the explanatory variables
      studied. The strength of the associations between the explanatory variables and
      MetS was estimated by Poisson regression with robust variance. RESULTS: MetS
      prevalence was 34.2 %; it was more prevalent in men (36.8 %) than in women (32.2
      %). In multivariate analysis, LBW was associated (prevalence ratio; 95 % CI) with
      MetS only in women (1.28; 1.24, 1.45). Shorter leg length was associated with
      MetS in both men (1.21; 1.09, 1.35 and 1.46; 1.29, 1.65 for low and medium
      lengths, respectively) and women (1.12; 1.00, 1.25 and 1.40; 1.22, 1.59 for low
      and medium lengths, respectively). Additional adjustments for age at menarche and
      BMI at 20 years old did not change the associations. CONCLUSIONS: Poor
      nutritional status as estimated by LBW and lower leg length in childhood was
      associated with a higher prevalence of MetS, although LBW was a significant
      factor only among women.

PMID- 29455689
TI  - INDUSTRY'S EXPERIENCES WITH THE SCIENTIFIC ADVICE OFFERED BY THE FEDERAL JOINT
      COMMITTEE WITHIN THE EARLY BENEFIT ASSESSMENT OF PHARMACEUTICALS IN GERMANY.
AB  - OBJECTIVES: Optional scientific advice (SA) for the early benefit assessment of
      pharmaceuticals is offered by the German decision maker, the Federal Joint
      Committee (FJC). The aim of this study was to elicit manufacturers' experiences
      with the SA procedures offered by the FJC to date. METHODS: A preliminary survey
      on a small sample size was conducted. Subsequently, a questionnaire comprising
      eight items, which was developed on the basis of that survey, was used. Data were
      analyzed using qualitative and quantitative approaches. RESULTS: The elicitation,
      including a sample of 25 percent of the completed advice, highlighted the
      following, regarding the process as well as to the content shortcomings of the SA
      procedures from an industrial perspective: inconsistencies, FJC's lack of
      expertise in conducting clinical trials, partially incomplete answers. and a low
      willingness of the FJC to engage in dialogue with industry were criticized. On
      the other hand, the majority of respondents expressed a positive attitude
      concerning unambiguousness, completeness, traceability, discussion atmosphere,
      and the protocol of the advice. Early SA, before pivotal trials start, showed a
      significantly higher completeness compared with late SA with respect to endpoints
      and study duration. Within 4 years the quality of FJC's propositions on some
      topics improved significantly. CONCLUSIONS: Only a few statistically significant
      differences were detectable between early versus late SA. A positive trend in
      industry's perception of the SA can be observed over time. A more active
      involvement of additional stakeholders and the incorporation of procedural
      elements from other healthcare systems could improve the quality of the SA
      offered by the FJC.

PMID- 29455690
TI  - Effect of Cerebral Perfusion Pressure on Acute Respiratory Distress Syndrome.
AB  - BACKGROUND: Increased cerebral perfusion pressure (CPP)>70 mmHg has been
      associated with acute respiratory distress syndrome (ARDS) after traumatic brain
      injury (TBI). Since this reported association, significant changes in ventilation
      strategies and fluid management have been accepted as routine critical care.
      Recently, individualized perfusion targets using autoregulation monitoring
      suggest CPP titration>70 mmHg. Given these clinical advances, the association
      between ARDS and increased CPP requires further delineation. OBJECTIVE: To
      determine the association between ARDS and increased CPP after TBI. METHODS: We
      conducted a single-center historical cohort study investigating the association
      of increased CPP and ARDS after TBI. We collected demographic data and
      physiologic data for CPP, intracranial pressure, mechanical ventilation,
      cumulative fluid balance and delta/driving pressure (DeltaP). We collected
      outcomes measures pertaining to duration of ventilation, intensive care unit
      admission length, hospitalization length and 6-month neurological outcome.
      RESULTS: In total, 113 patients with severe TBI and multimodal neuromonitoring
      were included. In total, 16 patients (14%) developed ARDS according to the Berlin
      definition. There was no difference in the mean CPP during the first 7 days of
      admission between patients who developed ARDS (74 mmHg SD 18 vs. 73 mmHg SD 18,
      p=0.86) versus those who did not. Patients who developed ARDS had a higher DeltaP
      (15 mmHg [5] vs. 12 mmHg [4], p=0.016) and lower lung compliance (35 ml/cmH2O
      [10] vs. 49 ml/cmH2O [18], p=0.024) versus those who did not. CONCLUSION: We did
      not observe an association between increased CPP and ARDS. Patients with ARDS had
      higher DeltaP and lower lung compliance.

PMID- 29455691
TI  - A new species of Parapharyngodon Chatterji, 1933 (Oxyuroidea: Pharyngodonidae),
      parasitic in Osteocephalus taurinus (Anura: Hylidae) from Brazil.
AB  - Parapharyngodon politoedi n. sp. is described here, based on specimens found in
      the large intestines of Osteocephalus taurinus from the Caxiuana National Forest,
      State of Para, Brazil. The new species is assigned to Parapharyngodon based on
      the presence of non-embryonated eggs with sub-terminal opercula, when in the
      ovijector. Parapharyngodon politoedi belongs to a group of species with three
      pairs of cloacal papillae and differs from its congeners by morphometric aspects,
      such as the length of the spicule, and the combination of the following
      morphological characters: ovaries never encircling the oesophagus, tail shape in
      females, cloacal lips, sharply pointed spicule and presence of genital cone. This
      is the second species of nematode reported to parasitize O. taurinus and the
      eleventh species of Parapharyngodon from hylids in the Neotropical region.

PMID- 29455692
TI  - A non-invasive assessment of skin carotenoid status through reflection
      spectroscopy is a feasible, reliable and potentially valid measure of fruit and
      vegetable consumption in a diverse community sample.
AB  - OBJECTIVE: To assess the feasibility, reliability and validity of reflection
      spectroscopy (RS) to assess skin carotenoids in a racially diverse sample.
      DESIGN: Study 1 was a cross-sectional study of corner store customers (n 479) who
      completed the National Cancer Institute Fruit and Vegetable Screener as well as
      RS measures. Feasibility was assessed by examining the time it took to complete
      three RS measures, reliability was assessed by examining the variation between
      three RS measures, and validity was examined by correlation with self-reported
      fruit and vegetable consumption. In Study 2, validity was assessed in a smaller
      sample (n 30) by examining associations between RS measures and dietary
      carotenoids, fruits and vegetables as calculated from a validated FFQ and plasma
      carotenoids. SETTING: Eastern North Carolina, USA. RESULTS: It took on average
      94.0 s to complete three RS readings per person. The average variation between
      three readings for each participant was 6.8 %. In Study 2, in models adjusted for
      age, race and sex, there were statistically significant associations between RS
      measures and (i) FFQ-estimated carotenoid intake (P<0.0001); (ii) FFQ-estimated
      fruit and vegetable consumption (P<0.010); and (iii) plasma carotenoids
      (P<0.0001). CONCLUSIONS: RS is a potentially improved method to approximate fruit
      and vegetable consumption among diverse participants. RS is portable and easy to
      use in field-based public health nutrition settings. More research is needed to
      investigate validity and sensitivity in diverse populations.

PMID- 29455693
TI  - Usefulness and safety of anakinra in refractory Kawasaki disease complicated by
      coronary artery aneurysm.
AB  - Kawasaki disease is an acute self-limited vasculitis of unknown aetiology. The
      prognosis depends mainly on coronary damage. There is no consensus regarding
      optimal adjunctive therapeutics for refractory forms to treatment by intravenous
      immunoglobulins and corticosteroids. We report the case of an 18-month-old infant
      with refractory Kawasaki disease complicated by diffuse aneurysms of coronary
      arteries and successfully treated by anakinra with partial regression of coronary
      aneurysms.

PMID- 29455694
TI  - A Study of Hospital Disaster Preparedness in South Yemen.
AB  - : Introduction Despite emphasis by disaster experts on the importance of disaster
      preparedness, disaster management in Yemen has attracted only a little attention.
      Most of the efforts have focused on post-disaster relief activities rather than
      the pre-disaster preparedness and risk reduction. Hospitals have a crucial role
      in emergency response and should be prepared. Thus, the aim of this study was
      intended to assess the hospital preparedness of Aden Capital, South Yemen against
      disasters. METHOD: A cross-sectional study was conducted in June 2016. The sample
      was all Aden City facilities with a total number of 10 hospitals: five public and
      five private hospitals. A survey was done by using the World Health Organization
      (WHO; Geneva, Switzerland) standards checklist 2011. RESULTS: The overall
      preparedness of Aden City hospitals to disasters fell at the unacceptable level
      of readiness, with an average mean of 46.6 (SD = 38.31; range 24-82). Of 10
      hospitals, two ranked insufficient while eight hospitals were at unacceptable
      levels of preparedness. CONCLUSION: All hospitals were noted grossly unprepared
      for potential disasters. Therefore, it is recommended that greater efforts be
      invested in creating a comprehensive strategy and national or local guidelines to
      establish an emergency management system based on the anticipated hazard and the
      needed resources. Naser WN , Ingrassia PL , Aladhrae S , Abdulraheem WA . A study
      of hospital disaster preparedness in South Yemen. Prehosp Disaster Med.
      2018;33(2):133-138.

PMID- 29455695
TI  - The empirical support for mindfulness-based interventions for common psychiatric
      disorders: a systematic review and meta-analysis.
AB  - Mindfulness-based interventions (MBIs) have become widely used for common mental
      disorders (CMDs) but the state of the evidence has not been sufficiently
      investigated. The aims for this study were: (1) to quantify the effect size of
      MBIs for CMDs in the acute phase; (2) to explore moderator variables; and (3) to
      evaluate the evidence status of MBIs for the CMDs it has been tried for. A
      comprehensive systematic review and meta-analysis of randomized controlled trials
      (RCTs) were conducted. RCTs that evaluated MBI and included patients with a
      primary manifest CMD was included. Methodological quality, the risk of bias,
      publication bias and evidence status were assessed. Literature searches gave 2448
      hits and 19 studies were included. MBIs were more effective than no treatment (g
      = 1.07) and treatment-as-usual (g = 0.40) but not in comparison to placebo (g =
      0.17) or other active treatments (g = -0.01). Methodological quality was
      negatively correlated with outcome. For all psychiatric disorders it has been
      tested, MBIs were judged to have weak or no empirical support. The conclusion of
      the study is that the evidence-base for MBIs for CMDs in the acute phase is weak.

PMID- 29455696
TI  - Targeting habits in anorexia nervosa: a proof-of-concept randomized trial.
AB  - BACKGROUND: Habits are behavioral routines that are automatic and frequent,
      relatively independent of any desired outcome, and have potent antecedent cues.
      Among individuals with anorexia nervosa (AN), behaviors that promote the starved
      state appear habitual, and this is the foundation of a recent neurobiological
      model of AN. In this proof-of-concept study, we tested the habit model of AN by
      examining the impact of an intervention focused on antecedent cues for eating
      disorder routines. METHODS: The primary intervention target was habit strength;
      we also measured clinical impact via eating disorder psychopathology and actual
      eating. Twenty-two hospitalized patients with AN were randomly assigned to 12
      sessions of either Supportive Psychotherapy or a behavioral intervention aimed at
      cues for maladaptive behavioral routines, Regulating Emotions and Changing Habits
      (REaCH). RESULTS: Covarying for baseline, REaCH was associated with a
      significantly lower Self-Report Habit Index (SRHI) score and significantly lower
      Eating Disorder Examination-Questionnaire (EDE-Q) global score at the end-of
      treatment. The end-of-treatment effect size for SRHI was d = 1.28, for EDE-Q was
      d = 0.81, and for caloric intake was d = 1.16. CONCLUSIONS: REaCH changed habit
      strength of maladaptive routines more than an active control therapy, and
      targeting habit strength yielded improvement in clinically meaningful measures.
      These findings support a habit-based model of AN, and suggest habit strength as a
      mechanism-based target for intervention.

PMID- 29455697
TI  - Meaningful Ways of Understanding and Measuring Change for People with Borderline
      Personality Disorder: A Thematic Analysis.
AB  - BACKGROUND: The effective treatment of Borderline Personality Disorder (BPD)
      presents healthcare providers with a significant challenge. The evidence base
      remains limited partially due to a lack of professional consensus and service
      user involvement regarding ways of measuring change. As a result, the limited
      evidence that is available draws on such a wide range of outcome measures, that
      comparison across treatment types is hindered, maintaining a lack of clarity
      regarding the clinical needs of this group. AIMS: This investigation aimed to
      follow the National Institute of Clinical Excellence (NICE, 2009) research
      recommendations by asking service users about meaningful change within their
      recovery. This forms a starting point for the future development of a tailored
      outcome measure. METHOD: Fifteen service users with a diagnosis of BPD
      participated in three focus groups across two specialist Personality Disorder
      services. The focus groups were analysed using Thematic Analysis. RESULTS: Two
      superordinate themes were synthesized from the data: (1) recovery to what?: 'How
      do you rewrite who you are?'; and (2) conditions for change. Each superordinate
      theme further consisted of three subordinate themes which elucidated the over
      arching themes. CONCLUSION: This investigation highlights the complex nature of
      measuring change in people who have received a BPD diagnosis. Further research is
      needed to develop meaningful ways of measuring change according to the needs and
      priorities of people with BPD.

PMID- 29455698
TI  - Stop the Bleed: The Effect of Hemorrhage Control Education on Laypersons'
      Willingness to Respond During a Traumatic Medical Emergency.
AB  - BACKGROUND: The "Stop the Bleed" campaign advocates for non-medical personnel to
      be trained in basic hemorrhage control. However, it is not clear what type of
      education or the duration of instruction needed to meet that requirement. The
      objective of this study was to determine the impact of a brief hemorrhage control
      educational curriculum on the willingness of laypersons to respond during a
      traumatic emergency. METHODS: This "Stop the Bleed" education initiative was
      conducted by the University of Texas Health San Antonio Office of the Medical
      Director (San Antonio, Texas USA) between September 2016 and March 2017.
      Individuals with formal medical certification were excluded from this analysis.
      Trainers used a pre-event questionnaire to assess participants knowledge and
      attitudes about tourniquets and responding to traumatic emergencies. Each
      training course included an individual evaluation of tourniquet placement, 20
      minutes of didactic instruction on hemorrhage control techniques, and hands-on
      instruction with tourniquet application on both adult and child mannequins. The
      primary outcome in this study was the willingness to use a tourniquet in response
      to a traumatic medical emergency. RESULTS: Of 236 participants, 218 met the
      eligibility criteria. When initially asked if they would use a tourniquet in real
      life, 64.2% (140/218) responded "Yes." Following training, 95.6% (194/203) of
      participants responded that they would use a tourniquet in real life. When
      participants were asked about their comfort level with using a tourniquet in real
      life, there was a statistically significant improvement between their initial
      response and their response post training (2.5 versus 4.0, based on 5-point
      Likert scale; P<.001). CONCLUSION: In this hemorrhage control education study, it
      was found that a short educational intervention can improve laypersons' self
      efficacy and reported willingness to use a tourniquet in an emergency. Identified
      barriers to act should be addressed when designing future hemorrhage control
      public health education campaigns. Community education should continue to be a
      priority of the "Stop the Bleed" campaign. Ross EM , Redman TT , Mapp JG , Brown
      DJ , Tanaka K , Cooley CW , Kharod CU , Wampler DA . Stop the bleed: the effect
      of hemorrhage control education on laypersons' willingness to respond during a
      traumatic medical emergency. Prehosp Disaster Med. 2018;33(2):127-132.

PMID- 29455699
TI  - Existing Approaches to Chemical, Biological, Radiological, and Nuclear (CBRN)
      Education and Training for Health Professionals: Findings from an Integrative
      Literature Review.
AB  - OBJECTIVES: This review was conducted to explore the literature to determine the
      availability, content, and evaluation of existing chemical, biological,
      radiological, and nuclear (CBRN) education programs for health professionals.
      METHODS: An integrative review of the international literature describing
      disaster education for CBRN (2004-2016) was conducted. The following relevant
      databases were searched: Proquest, Pubmed, Science Direct, Scopus, Journals @
      OVID, Google Scholar, Medline, and Ichuschi ver. 5 (Japanese database for health
      professionals). The search terms used were: "disaster," "chemical," "biological,"
      "radiological," "nuclear," "CBRN," "health professional education," and "method."
      The following Medical Subject Headings (MeSH) terms, "education," "nursing,"
      "continuing," "disasters," "disaster planning," and "bioterrorism," were used
      wherever possible and appropriate. The retrieved articles were narratively
      analyzed according to availability, content, and method. The content was
      thematically analyzed to provide an overview of the core content of the training.
      RESULTS: The literature search identified 619 potentially relevant articles for
      this study. Duplicates (n=104) were removed and 87 articles were identified for
      title review. In total, 67 articles were discarded, yielding 20 articles for all
      text review, following 11 studies were retained for analysis, including one
      Japanese study. All articles published in English were from the USA, apart from
      the two studies located in Japan and Sweden. The most typical content in the
      selected literature was CBRN theory (n=11), followed by studies based on incident
      command (n=8), decontamination (n=7), disaster management (n=7), triage (n=7),
      personal protective equipment (PPE) use (n = 5), and post-training briefing
      (n=3). CONCLUSION: While the CBRN training course requires the participants to
      gain specific skills and knowledge, proposed training courses should be
      effectively constructed to include approaches such as scenario-based simulations,
      depending on the participants' needs. Kako M , Hammad K , Mitani S , Arbon P .
      Existing approaches to chemical, biological, radiological, and nuclear (CBRN)
      education and training for health professionals: findings from an integrative
      literature review. Prehosp Disaster Med. 2018;33(2):182-190.

PMID- 29455700
TI  - Addiction: a brief history of an idea.

PMID- 29455701
TI  - Estimating the pathways through which maternal education affects stunting:
      evidence from an urban cohort in South Africa.
AB  - OBJECTIVE: To estimate the determinants of stunting using rich data from a birth
      cohort study from urban South Africa and to examine the various mechanisms, both
      proximate and distal, through which maternal education affects stunting. DESIGN:
      Multivariate regression analysis using birth cohort data, where the outcome
      variable was stunting at age 2 years, and multiple mediator analysis to identify
      pathways from maternal education to stunting. SETTING: South Africa's largest
      metropolitan area, Soweto-Johannesburg. SUBJECTS: Participants of Birth to Twenty
      Plus, a longitudinal cohort study of children born in 1990 (n 691). RESULTS: In
      multivariate analysis, the birth weight Z-score (-0.084; P<0.001; 95 % CI -0.11, 
      0.06), the mother's openness towards modern health care, captured by a
      vaccination score (-0.05; P=0.04; 95 % CI -0.10, -0.00), and a better-quality
      care environment (-0.015; P=0.04; 95 % CI -0.03, -0.00) were found to be
      negatively associated with stunting. Having experienced symptoms of illness
      related to ears and eyes increased the risk of stunting (0.038; P=0.01; 95 % CI
      0.01, 0.07). Results of the mediation analysis showed that maternal education had
      an indirect effect on stunting largely through socio-economic status and the
      antenatal environment (measured by the birth weight Z-score). CONCLUSIONS:
      Overall, many of the factors that were protective against stunting in the final
      analysis, whether they operated through maternal education or not, were related
      to the mother's contribution to the child's life. This reinforces the idea that
      to minimise stunting, enhanced antenatal and postnatal services to better support
      and empower mothers may be important.

PMID- 29455702
TI  - Room 328.

PMID- 29455703
TI  - The development of a single health-endorsement logo for South Africa.
AB  - OBJECTIVE: To develop health-endorsement logos (HEL) for food products indicating
      healthy choices based on the South African nutrient profile model and to pilot
      test these logos with consumers. DESIGN: Multistage mixed-methods design.
      SETTING: Cape Town, South Africa. SUBJECTS: Nine focus group discussions (FGD)
      were conducted with adult consumers to explore what types of HEL are preferred
      and why. Based on the findings, ten HEL were designed by a graphic design team. A
      modified Delphi technique, conducted with experts in the fields of nutrition and
      food science, was employed to eliminate lowest-scoring HEL and to improve the
      design of the remaining logos. Participants from the initial FGD participated in
      pilot testing the improved logos. RESULTS: Participants from FGD (n 67) were
      positive about a single HEL, stating it would make food labelling less confusing
      as they did not understand the various HEL used. Participants indicated the logo
      should include wording related to 'healthy choice' or 'better choice' and
      pictures/symbols related to health and/or food. During two rounds of scoring and
      comments by experts (n 19), five logos were eliminated and the design of the
      remaining five improved. Three of five remaining logos received overall rankings
      of 3.08/5, 3.28/5 and 3.39/5, respectively, during FGD (n 36) in the pilot
      testing phase. CONCLUSION: HEL were designed and consumer tested. Three designs
      were submitted to the national Department of Health to consider for
      implementation, after further testing, as a tool to assist in addressing the high
      incidence of non-communicable diseases in South Africa.

PMID- 29455704
TI  - Role of parental education in reduction of prevalence of childhood undernutrition
      in Bangladesh.
AB  - OBJECTIVE: Despite progress, levels of malnutrition among children in Bangladesh
      are among the highest in the world and this is one of the major causes of death
      in children. The pace of reduction in the prevalence of undernutrition among
      children is still relatively low. The present study aimed to examine the
      association between parental education and childhood undernutrition among
      Bangladeshi children under 5 years of age when adjusting for potential risk
      factors. DESIGN: The data set was extracted from a nationally representative
      survey based on a cross-sectional study, the Bangladesh Demographic and Health
      Survey (BDHS) 2014. SETTING: The base survey was conducted using a two-stage
      stratified sample of households. In the first stage, 600 enumeration areas (EA)
      were selected with probability proportional to EA size (207 EA from urban areas,
      393 EA from rural areas). SUBJECTS: A total of 7173 children under 5 years from
      17 863 households were considered for the analysis. A modified Poisson regression
      model was implemented to the data for assessing the relationship between parental
      education and childhood undernutrition when demographic and socio-economic
      covariates for the child, parents, households and clustering were adjusted.
      RESULTS: Higher parental education level was associated with lower levels of
      stunting and underweight, but not with wasting. Maternal and paternal education
      were both significantly associated with the reduction in prevalence of childhood
      undernutrition in Bangladesh. CONCLUSIONS: Paternal education appears equally as
      important as maternal education in reducing undernutrition prevalence among
      children under 5 years in Bangladesh.

PMID- 29455705
TI  - Barriers to fruit and vegetable consumption among farmers' market incentive
      programme users in Illinois, USA.
AB  - OBJECTIVE: Previous research indicates that low-income individuals often struggle
      to consume the recommended amount of fruits and vegetables (F&V). LINK Up
      Illinois is a farmers' market incentive programme that aims to increase F&V
      consumption among Supplemental Nutrition Assistance Program (SNAP) recipients by
      improving access to and affordability of locally grown foods. The present
      research aimed to identify barriers to F&V consumption that exist among users of
      the LINK Up Illinois programme. DESIGN: Cross-sectional. SETTING: Farmers'
      markets in Chicago, Springfield, Northbrook, Woodstock, Aurora and Urbana, IL.
      SUBJECTS: In 2016, a volunteer sample of 140 LINK Up Illinois users (mean age
      42.5 years; 81.7 % female; 28.7 % African American; 44.0 % obese) completed a
      survey at participating farmers' markets across the state. Information on
      demographics, food shopping behaviours, programme satisfaction, barriers to F&V
      consumption and frequency of F&V consumption was collected and examined. RESULTS:
      Approximately 23 % of survey participants reported consuming F&V >=3 times/d. The
      barriers to F&V consumption most often reported by survey participants were the
      cost of F&V (29.5 %), spoilage (18.6 %), knowing how to cook F&V (8.7 %) and not
      thinking about F&V when hungry (8.6 %). Results from multivariable-adjusted
      logistic regression models suggested that reporting one or more barriers was
      associated with reduced odds of consuming vegetables >=3 times/d, but not fruits.
      CONCLUSIONS: Cost, spoilage and knowledge of cooking are key barriers to F&V
      consumption that exist among LINK Up Illinois users. Strategies are needed to
      mitigate these barriers and increase F&V consumption in this population.

PMID- 29455706
TI  - Review: The potential of seminal fluid mediated paternal-maternal communication
      to optimise pregnancy success.
AB  - Artificial insemination has been a landmark procedure in improving animal
      agriculture over the past 150 years. The utility of artificial insemination has
      facilitated a rapid improvement in animal genetics across agricultural species,
      leading to improvements of growth, health and productivity in poultry, swine,
      equine and cattle species. The utility of artificial insemination, as with all
      assisted reproductive technologies side-steps thousands of years of evolution
      that has led to the development of physiological systems to ensure the
      transmission of genetics from generation to generation. The perceived
      manipulation of these physiological systems as a consequence of assisted
      reproduction are points of interest in which research could potentially improve
      the success of these technologies. Indeed, seminal fluid is either removed or
      substantially diluted when semen is prepared for artificial insemination in
      domestic species. Although seminal fluid is not a requirement for pregnancy,
      could the removal of seminal fluid from the ejaculate have negative consequences
      on reproductive outcomes that could be improved to further the economic benefit
      of artificial insemination? One such potential influence of seminal fluid on
      reproduction stems from the question; how does the allogeneic foetus survive
      gestation in the face of the maternal immune system? Observation of the maternal
      immune system during pregnancy has noted maternal immune tolerance to paternal
      specific antigens; a mechanism by which the maternal immune system tolerates
      specific paternal antigens expressed on the foetus. In species like human or
      rodent, implantation occurs days after fertilisation and as such the mechanisms
      to establish antigen-specific tolerance must be initiated very early during
      pregnancy. We and others propose that these mechanisms are initiated at the time
      of insemination when paternal antigens are first introduced to the maternal
      immune system. It is unclear whether such mechanisms would also be involved in
      domestic species, such as cattle, where implantation occurs weeks later in
      gestation. A new paradigm detailing the importance of paternal-maternal
      communication at the time of insemination is becoming evident as it relates to
      maternal tolerance to foetal antigen and ultimately pregnancy success.

PMID- 29455707
TI  - The alignment of law, practice and need in suicide prevention.
AB  - Help-seeking is important for patients with suicidal ideation. Currently, a risk
      management paradigm is used with patients who express suicidality; however, this
      may limit support and increase stigma, reducing future help-seeking. Coping
      planning is proposed as a paradigm shift that overcomes these problems by
      focusing on patient needs and strengths. Declaration of interest None.

PMID- 29455708
TI  - Developing Public Health Initiatives through Understanding Motivations of the
      Audience at Mass-Gathering Events.
AB  - This report identifies what is known about audience motivations at three
      different mass-gathering events: outdoor music festivals, religious events, and
      sporting events. In light of these motivations, the paper discusses how these can
      be harnessed by the event organizer and Emergency Medical Services. Lastly,
      motivations tell what kinds of interventions can be used to achieve an
      understanding of audience characteristics and the opportunity to develop tailor
      made programs to maximize safety and make long-lasting public health
      interventions to a particular "cohort" or event population. A lot of these will
      depend on what the risks/hazards are with the particular populations in order to
      "target" them with public health interventions. Audience motivations tell the
      event organizer and Emergency Medical Services about the types of behaviors they
      should expect from the audience and how this may affect their health while at the
      event. Through these understandings, health promotion and event safety messages
      can be developed for a particular type of mass-gathering event based on the
      likely composition of the audience in attendance. Health promotion and providing
      public information should be at the core of any mass-gathering event to minimize
      public health risk and to provide opportunities for the promotion of healthy
      behaviors in the local population. Audience motivations are a key element to
      identify and agree on what public health information is needed for the event
      audience. A more developed understanding of audience behavior provides critical
      information for event planners, event risk managers, and Emergency Medical
      Services personnel to better predict and plan to minimize risk and reduce patient
      presentations at events. Mass-gathering event organizers and designers intend
      their events to be positive experiences and to have meaning for those who attend.
      Therefore, continual vigilance to improve public health effectiveness and
      efficiency can become best practice at events. Through understanding the
      motivations of the audience, event planners and designers, event risk managers,
      and emergency medical personnel may be better able to understand the motivation
      of the audience and how this might impact on audience behavior at the event.
      Hutton A , Ranse J , Munn MB . Developing public health initiatives through
      understanding motivations of the audience at mass-gathering events. Prehosp
      Disaster Med. 2018;33(2):191-196.

PMID- 29455710
TI  - The following abstracts were presented as posters at the 2017 NEI Congress.
AB  - Congratulations to the scientific poster winners: 1 st Place: #178-Gender
      Differences in Prodromal Symptoms of Dementia 2 nd Place: #146-Effect of Heroin
      Use on Changes of Brain Functions As Measured by fMRI, a Systematic Review 3 rd
      Place: #185-Second Generation Antipsychotics and Catatonia: A Literature Review.

PMID- 29455709
TI  - What do They Know? Guidelines and Knowledge Translation for Foreign Health Sector
      Workers Following Natural Disasters.
AB  - : Introduction The incidence of natural disasters is increasing worldwide, with
      countries the least well-equipped to mitigate or manage them suffering the
      greatest losses. Following natural disasters, ill-prepared foreign responders may
      become a burden to the affected population, or cause harm to those needing help.
      Problem The study was performed to determine if international guidelines for
      foreign workers in the health sector exist, and evidence of their implementation.
      METHODS: A structured literature search was used to identify guidelines for
      foreign health workers (FHWs) responding to natural disasters. Analysis of semi
      structured interviews of health sector responders to the 2015 Nepal earthquake
      was then performed, looking at preparation and field activities. RESULTS: No
      guidelines were identified to address the appropriate qualifications of, and
      preparations for, international individuals participating in disaster response in
      the health sector. Interviews indicated individuals choosing to work with
      experienced organizations received training prior to disaster deployment and
      described activities in the field consistent with general humanitarian
      principles. Participants in an ad hoc team (AHT) did not. CONCLUSIONS: In spite
      of need, there is a lack of published guidelines for potential international
      health sector responders to natural disasters. Learning about disaster response
      may occur only after joining a team. Dunin-Bell O . What do they know? Guidelines
      and knowledge translation for foreign health sector workers following natural
      disasters. Prehosp Disaster Med. 2018;33(2):139-146.

PMID- 29455711
TI  - Evaluation of the Benefits of De-Escalation for Patients with Sepsis in the
      Emergency Intensive Care Unit.
AB  - PURPOSE: Although the 2016 Japanese guidelines for the management of sepsis
      recommend de-escalation of treatment after identification of the causative
      pathogen, adherence to this practice remain unknown. The objective of this study
      was to evaluate the benefits of de-escalating treatment for sepsis patients at an
      advanced critical care and emergency medical centre. METHODS: Based on electronic
      patient information, 85 patients who were transported to the centre by ambulance,
      and diagnosed with sepsis between January 2008 and September 2013 were enrolled
      and evaluated. Patients were divided into two groups with and without de
      escalation, and comparisons were conducted for several variables, including
      length of hospital stay, and length of antibiotic administration. Two types of
      subgroup analysis were conducted between patients with septic shock or positive
      blood cultures. Statistical analysis was conducted using chi-square and Mann
      Whitney U tests. RESULTS: The length of hospital stay after diagnosis was
      significantly shorter for the de-escalation group than for the non-de-escalation
      group. In the subgroup analysis, de-escalation for blood culture-positive
      patients was beneficial in terms of the length of hospital stay and length of
      antibiotic administration. CONCLUSIONS: The findings of this study suggest that
      sepsis treatment de-escalation is beneficial for treatment efficacy and
      appropriate use of antibiotics. This article is open to POST-PUBLICATION REVIEW.
      Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the
      issue's contents page.

PMID- 29455712
TI  - Serving the Underserved: The Health and Well-Being of Adolescent and Young Adult
      Males.

PMID- 29455713
TI  - Age-Specific Global Prevalence of Hepatitis B, Hepatitis C, HIV, and Tuberculosis
      Among Incarcerated People: A Systematic Review.
AB  - PURPOSE: This study aims to compare the global prevalence of hepatitis B,
      hepatitis C, HIV, and tuberculosis in incarcerated adolescents and young adults
      (AYAs) and older prisoners. METHODS: This study is a systematic review and meta
      analysis of studies reporting the age-specific prevalence of each infection in
      prisoners. We grouped age-specific prevalence estimates into three overlapping
      age categories: AYA prisoners (<25 years), older prisoners (>=25 years), and
      mixed category (spanning age 25 years). We used random effects meta-analysis to
      estimate the relative risk (RR) of each infection in AYAs versus older prisoners.
      RESULTS: Among 72 studies, there was marked heterogeneity in prevalence estimates
      among AYA prisoners for all infections: hepatitis B (.4%-25.2%), hepatitis C (.0%
      70.6%), HIV (.0%-15.8%), and active tuberculosis (.0%-3.7%). The pooled
      prevalence of HIV (RR = .39, 95% confidence interval .29-.53, I2 = 79.2%) and
      hepatitis C (RR = .51, 95% confidence interval .33-.78, I2 = 97.8%) was lower in
      AYAs than in older prisoners. CONCLUSIONS: The prevalence of HIV and hepatitis C
      is lower in AYA prisoners than in older prisoners. Despite lower prevalence,
      acquisition begins early among incarcerated populations. There is an urgent need
      for targeted, age-appropriate prevention, treatment, and harm reduction measures
      in and beyond custodial settings to reduce the incidence of infection in these
      extremely vulnerable young people.

PMID- 29455714
TI  - Using Time-Varying Effect Modeling to Examine Age-Varying Gender Differences in
      Coping Throughout Adolescence and Emerging Adulthood.
AB  - PURPOSE: Little is known about how and when coping trajectories differ between
      males and females. The current study aimed to examine gender differences in the
      use of specific coping strategies across developmental ages using time-varying
      effect modeling (TVEM) in a large, diverse community sample. METHODS: A
      longitudinal study following adolescents across 4 years of high school and 5
      years post graduation (N = 1,251) was combined with a nationally representative
      cross-sectional study of 18- to 22-year-olds (N = 595) to examine changes in
      gender differences in the use of coping strategies between ages 13 and 25. The
      same coping questionnaire was administered to both samples. TVEM was used to
      examine the age-varying prevalence rates of coping in males and females. RESULTS:
      Gender differences were greatest during middle-to-late adolescence (15-19 years)
      for active coping, social support seeking, planning, and venting emotions.
      Females reported greater use of these strategies than males, but males' use
      increased over time and became equivalent to females after the age of ~19-20.
      Gender differences in the use of humor did not emerge until the age of 22, at
      which point the use of humor increased continuously among males but remained
      stable among females. The use of denial was fairly stable across time, with no
      gender differences at any age. CONCLUSIONS: Findings highlight the utility of
      TVEM for advancing our knowledge on gender and coping across developmental time,
      as males and females used coping strategies at differing rates throughout
      adolescence and emerging adulthood. Implications for tailoring gender- and age
      specific intervention efforts to improve coping and related health behaviors are
      discussed.

PMID- 29455715
TI  - Addressing Gender Socialization and Masculinity Norms Among Adolescent Boys:
      Policy and Programmatic Implications.

PMID- 29455716
TI  - How Collegiate Fraternity and Sorority Involvement Relates to Substance Use
      During Young Adulthood and Substance Use Disorders in Early Midlife: A National
      Longitudinal Study.
AB  - PURPOSE: To assess how social fraternity involvement (i.e., membership and
      residence) in college relates to substance use behaviors and substance use
      disorder symptoms during young adulthood and early midlife in a national sample.
      METHODS: National multi-cohort probability samples of US high school seniors from
      the Monitoring the Future study were assessed at baseline (age 18) and followed
      longitudinally via self-administered surveys across seven follow-up waves to age
      35. The longitudinal sample consisted of 7,019 males and 8,661 females, of which
      10% of males and 10% of females were active members of fraternities or sororities
      during college. RESULTS: Male fraternity members who lived in fraternity houses
      during college had the highest levels of binge drinking and marijuana use
      relative to non-members and non-students in young adulthood that continued
      through age 35, controlling for adolescent sociodemographic and other
      characteristics. At age 35, 45% of the residential fraternity members reported
      alcohol use disorder (AUD) symptoms reflecting mild to severe AUDs; their
      adjusted odds of experiencing AUD symptoms at age 35 were higher than all other
      college and noncollege groups except non-residential fraternity members.
      Residential sorority members had higher odds of AUD symptoms at age 35 when
      compared with their noncollege female peers. CONCLUSIONS: National longitudinal
      data confirm binge drinking and marijuana use are most prevalent among male
      fraternity residents relative to non-members and non-students. The increased risk
      of substance-related consequences associated with fraternity involvement was not
      developmentally limited to college and is associated with higher levels of long
      term AUD symptoms during early midlife.

PMID- 29455717
TI  - The Role of Hypermasculinity, Token Resistance, Rape Myth, and Assertive Sexual
      Consent Communication Among College Men.
AB  - PURPOSE: A greater understanding of how college men's gendered beliefs and
      communication styles relate to their sexual consent attitudes and intentions is
      essential within the shifting context of negative to affirmative consent policies
      on college campuses. The results of this study can be used to help design more
      effective sexual consent interventions. METHODS: Three hundred seventy
      undergraduate college men completed cross-sectional online surveys. Hierarchical
      multiple regression examined how hypermasculinity, token resistance, rape myth
      acceptance, and sexual communication assertiveness were associated with consent
      related attitudes, intentions, and interpretations. RESULTS: Bivariate
      correlations among all variables were significant. In multivariate analyses,
      sexual communication assertiveness was positively associated with all consent
      outcomes, and token resistance and rape myth acceptance were negatively
      associated with some. Hypermasculinity was not a significant factor. CONCLUSIONS:
      Programs seeking to improve sexual consent communication among college men should
      reduce destructive beliefs and encourage sexually assertive communication.

PMID- 29455718
TI  - Precollege Sexual Violence Perpetration and Associated Risk and Protective
      Factors Among Male College Freshmen in Georgia.
AB  - PURPOSE: Sexual violence (SV) perpetration on college campuses is a serious and
      prevalent public health issue in the U.S. In response, incoming male freshmen are
      mandated to receive SV prevention programming. To provide a more effective
      response, however, we need to understand the SV behaviors of male freshmen before
      they arrive on campus and the associated factors that contribute to risk and that
      afford protection, areas that have received limited attention. METHODS: Male
      freshmen (N = 1,133) across 30 selected 4-year colleges and universities
      throughout the state of Georgia were recruited for a longitudinal study on SV
      perpetration. Levels of precollege SV as well as a range of covariates were
      assessed at baseline. Self-reported SV perpetrators were compared with
      nonperpetrators on demographic and hypothesized covariates deemed either risk or
      protective; then risk and protective models were analyzed using binary logistic
      regression. RESULTS: Weighted analyses revealed that 19.3% self-reported
      perpetrating SV before college. Before starting college, young men who reported
      more sexual media consumption, heavy episodic drinking, hypermasculine beliefs,
      and peers who endorsed SV were more likely to have a history of SV perpetration
      at college matriculation. Alternatively, men with more knowledge of effective
      sexual consent and stronger family functioning were less likely to arrive to
      college with an SV perpetration history. CONCLUSIONS: A significant proportion of
      incoming male freshmen have perpetrated SV previously. Colleges and universities
      need to assess incoming freshmen for risk behaviors and negative beliefs and to
      offer both primary and secondary preventions to more effectively reduce further
      perpetration.

PMID- 29455720
TI  - A Gender Lens on the Health and Well-being of Young Males.

PMID- 29455719
TI  - Community Engagement and Venue-Based Sampling in Adolescent Male Sexually
      Transmitted Infection Prevention Research.
AB  - OBJECTIVES: Middle adolescent males are a difficult group to recruit for
      community sexually transmitted infection (STI) prevention research. We describe a
      process of community engagement, and venue-based sampling of 14-17-year-old
      adolescent males, and compare rates of STIs and STI risk behaviors by venue.
      METHODS: Community engagement consisted of (1) informational meetings with
      organizations; (2) participation in community meetings and events; (3) hiring
      community members as study personnel; and (4) an adolescent advisory board
      recruited from the community. Venues were identified and assessed at different
      times of the day and days of the week using a structured tool. At selected
      venues, males ages 14-17 years were invited to participate in a brief survey and
      provide a urine sample and an optional anal swab for DNA-based STI testing.
      RESULTS: Venues were assessed (n = 249), and 31 were selected for recruitment,
      including parks, apartment complexes, community events, entertainment venues, a
      community school, and community programs for LGBT (gay, lesbian, bisexual,
      transgender) and adjudicated youth. We enrolled 667 participants, average age
      15.7 years. Participants reported high rates of sexual and STI risk behaviors,
      but had low rates of STIs. These rates differed by venue, with more structured
      venues recruiting youth reporting fewer STI risk behaviors and less structured
      venues within the highest STI prevalence zip code recruiting youth reporting more
      STI risk behaviors. CONCLUSION: Venue-based sampling is a feasible mechanism to
      target recruitment and enrollment adolescent males with high STI risk behaviors
      in community settings, with risk profiles varying by setting.

PMID- 29455721
TI  - Fit4YAMs: Structuring a Lifestyle Intervention for Rural Overweight and Obese
      Young Adult Males Using Participatory Design.
AB  - PURPOSE: Young adult males (YAMs) are understudied with respect to lifestyle
      interventions to address overweight and obesity in this group. This study reports
      on the participatory design of the structure and delivery of the Fit4YAMs text
      message-based lifestyle intervention for 18- to 25-year-old rural YAMs in
      Australia. METHODS: Two semi-structured focus group discussions were held with
      six overweight or obese YAMs. Sessions explored their preferences for the
      structure and delivery of a weight loss intervention. Focus groups were recorded,
      and the contents transcribed verbatim for thematic analysis. RESULTS: The YAMs
      were unanimous in their preference for a highly personalized intervention
      program, complete with personalized goal setting, personalized motivation and
      engagement strategies, and personalized text message content. A text message
      frequency of three-four messages per week was deemed optimal for this group.
      Minimal direct contact by the intervention team was requested, but with clear
      guidelines and reminders of key contacts whom they could contact should they
      require help and guidance. The YAMs also agreed that a comprehensive goal setting
      session and personalization session prior to commencement of the intervention
      would be best. CONCLUSIONS: To engage rural YAMs in lifestyle interventions, a
      high degree of personalization of the program appears important. Although
      initially more time and resource intensive than a less personalized approach, it
      is essential to identify strategies to prevent and reverse weight gain in this
      hard to engage group. Maximizing their engagement using a more personalized
      approach could be the key to promoting long-term health outcomes in this group.

PMID- 29455722
TI  - Computer-Assisted Motivational Interviewing Intervention to Facilitate Teen
      Pregnancy Prevention and Fitness Behavior Changes: A Randomized Trial for Young
      Men.
AB  - PURPOSE: Despite recent declines, teen unintended pregnancy and sexually
      transmitted infections in the United States remain at levels higher than
      comparable nations. Initiatives to prevent teen pregnancy have focused primarily
      on female adolescents; how to effectively engage young men to reduce their risk
      of fathering a teen pregnancy has not been well studied. We proposed to adapt an
      innovative computer-assisted motivational interviewing (CAMI) intervention,
      originally designed and tested with young women, for use with young men, aged 15
      24 years, to reduce their risk of fathering a teen pregnancy. This manuscript
      describes the design of a CAMI intervention for young men aimed at preventing
      teen pregnancy and improving fitness. METHODS: This randomized controlled trial
      will recruit 945 sexually active young men between the ages of 15 and 24 years
      from three health centers in New York City. Participants will be assigned by
      permuted block randomization to two study arms: one aimed at reducing involvement
      in unintended teen pregnancy (CAMI-teen pregnancy prevention) and the other at
      improving overall fitness (CAMI-Fitness). Except for topic, both intervention
      arms will provide four sessions of Motivational Interviewing coaching and use a
      mobile app to track behavior and set goals. We will assess young men's sexual and
      reproductive health behaviors and fitness at baseline, 12, 24, 36, and 64 weeks
      using a mobile device app created for the study. RESULTS: Pending ongoing study.
      CONCLUSIONS: Results from the study are expected to enhance our understanding of
      the efficacy of CAMI to enhance young men's reproductive health and fitness
      behaviors.

PMID- 29455723
TI  - Addressing a Critical Gap in U.S. National Teen Pregnancy Prevention Programs:
      The Acceptability and Feasibility of Father-Based Sexual and Reproductive Health
      Interventions for Latino Adolescent Males.
AB  - PURPOSE: The purpose of the research was to examine the feasibility and
      acceptability of a father-based sexual and reproductive health intervention
      designed to reduce sexual and reproductive (SRH) disparities and increase correct
      and consistent condom use among Latino adolescent males. METHODS: The current
      study conducted in-depth semi-structured interviews with Latino father-son dyads
      (N=30) designed to elicit perspectives on communication regarding sex and condom
      use. In addition, the interview protocol included father-son preferences
      regarding paternal involvement in condom instruction and perceived obstacles and
      advantages of father direct involvement in education efforts designed to increase
      correct and consistent condom use among their adolescent sons. Three independent
      coders conducted both vertical and horizontal analyses of the data to identify
      emergent themes and reach theoretical saturation. RESULTS: The main findings from
      this study suggest that Latino fathers can be impactful in shaping Latino
      adolescent male sexual decision-making and correct and consistent condom use.
      However, our data highlight that while both feasible and acceptable, Latino
      fathers identify needing additional support in how best to communicate and seek
      opportunities to master their own knowledge and skills regarding condom use and
      effective communication with their adolescent sons about sex. CONCLUSIONS: Latino
      father-based interventions represent an acceptable and feasible option for
      building upon the recent success of U.S. national efforts to reduce teen
      pregnancy rates and STI disparities among Latino youth. However, there exists a
      need for father-based programs that will support Latino fathers in best educating
      their sons about condom use and better addressing their SRH. Ongoing national
      efforts to reduce Latino teen SRH disparities warrant the consideration of father
      son interventions for Latino adolescent males in the United States.

PMID- 29455724
TI  - Adolescent and Young Adult Male Mental Health: Transforming System Failures Into
      Proactive Models of Engagement.
AB  - Adolescent and young adult men do poorly on indicators of mental health evidenced
      by elevated rates of suicide, conduct disorder, substance use, and interpersonal
      violence relative to their female peers. Data on global health burden clearly
      demonstrate that young men have a markedly distinct health risk profile from
      young women, underscoring different prevention and intervention needs. Evidence
      indicates that boys disconnect from health-care services during adolescence,
      marking the beginning of a progression of health-care disengagement and
      associated barriers to care, including presenting to services differently,
      experiencing an inadequate or poorly attuned clinical response, and needing to
      overcome pervasive societal attitudes and self-stigma to access available
      services. This review synthesizes key themes related to mental ill health in
      adolescent boys and in young adult men. Key social determinants are discussed,
      including mental health literacy, self-stigma and shame, masculinity, nosology
      and diagnosis, and service acceptability. A call is made for focused development
      of policy, theory, and evaluation of targeted interventions for this population,
      including gender-synchronized service model reform and training of staff,
      including the e-health domain. Such progress is expected to yield significant
      social and economic benefits, including reduction to mental ill health and
      interpersonal violence displayed by adolescent boys and young adult men.

PMID- 29455725
TI  - Anti-inflammatory effect of external use of escin on cutaneous inflammation:
      possible involvement of glucocorticoids receptor.
AB  - Escin, as an internally applied anti-inflammatory agent, has been widely used in
      the treatment of inflammation and edema resulting from trauma or operation in the
      clinic. However, the effect of its external use on cutaneous inflammation and
      edema remains unexplored. In the present study, the anti-inflammatory and anti
      edematous effects of external use of escin were studied in carrageenan-induced
      paw edema and histamine-induced capillary permeability in rats, paraxylene
      induced ear swelling in mice, and cotton pellet-induced granuloma in rats.
      Effects of external use of escin gel on prostaglandin E2 (PGE2), tumor necrosis
      factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) were determined by
      ELISA. The anti-inflammatory mechanism was explored by detecting the expression
      of glucocorticoid receptor (GR) with Western blotting and Real-time PCR analyses,
      with further exploration of nuclear factor-kappaB (NF-kappaB), p38 mitogen
      activated protein kinase (P38MAPK) and activator protein-1 (AP-1) expressions. We
      demonstrated that external use of escin showed significant anti-inflammatory
      effects on acute and chronic inflammation in different animal models and its anti
      inflammatory effects might be related to down-regulation of PGE2, TNF-alpha, and
      IL-1beta. The results also showed that escin exerted its anti-inflammatory
      effects by promoting the expression of GR, with the possible mechanism being
      inhibition of the expressions of GR-related signaling molecules such as NF-kappaB
      and AP-1.

PMID- 29455726
TI  - Synthesis and biological evaluation of novel tanshinone IIA derivatives for
      treating pain.
AB  - Due to ineffectiveness and side effects of existing analgesics, chronic pain has
      become one of the most complex and difficult problems in the clinic.
      Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid
      system and has been identified as a potential target for the treatment of pain.
      In the present study, we designed and synthesized twelve tanshinone IIA analogs
      and screened their activity against MAGL. Selected compounds were tested for
      analgesic activity in vivo, with the acetic acid writhing test model. Among the
      test compounds, compound III-3 (IC50 120 nmol.L-1) showed significant activity
      against MAGL and ameliorated the clinical progression in the mouse pain model.
      Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide,
      demonstrated improved solubility relative to tanshinone IIA.

PMID- 29455727
TI  - Enhancement of gut permeation of amoxicillin with Nigella sativa seed extract and
      its phytochemical screening.
AB  - The seeds of Nigella sativa Linn. (Ranunculaceae), commonly known as Black cumin,
      are predominantly used as carminative, antispasmodic, and stimulant. The main
      objective of the present study was to evaluate the effect of N. sativa seed
      extract on the permeation of co-infused amoxicillin across the gut wall. The
      methanolic extract of N. sativa improved intestinal permeability of amoxicillin
      in in-vitro experiments in a dose-dependent manner. Two new glycosides, decanyl
      nigelloic acid diglucoside [n-decanyl-3-aldehydic-4-methoxy-5-hydroxy benzoate-5
      beta-D-glucofuranosyl (2->1)-beta-D-glucopyranosyl-(2->1)-beta-D
      glucopyranoside]] and nigelabdienoyl triglucoside [homo-labd-5, 9(11)-dien-16
      onyl-beta-D-glucopyranosyl (2->1)-beta-D-glucopyranosyl (2->1)-beta-D
      glucopyranoside], along with seven known fatty acid glycerides/esters, were
      isolated from the gut permeation enhancing extract. The structures of these new
      glycosides were elucidated by detailed spectroscopic analyses.

PMID- 29455728
TI  - Novel triterpene saponins isolated from Clematis mandshurica and their inhibitory
      activities on NO production.
AB  - Four new triterpene saponins, mandshunosides F-I (1-4), together with five known
      compounds (5-9), were isolated from the roots and rhizomes of Clematis
      mandshurica. Their structures were elucidated on the basis of spectroscopic
      evidences and hydrolysis products. Bisdesmosidic saponin (3-9) showed modest
      suppression of NO production with the inhibition ratios in the range of 51.3%-
      64.6% at 50 MUmol.L-1, whereas monodesmosidic saponins with a free carboxyl group
      at C-28 (1 and 2) showed potent inhibitory activities with IC50 values being 12.7
      and 8.3 MUmol.L-1, respectively.

PMID- 29455729
TI  - Three new alkaloids isolated from the stem tuber of Pinellia pedatisecta.
AB  - The present study was designed to determine the chemical constituents of the stem
      tuber of Pinellia pedatisecta. The chemical constituents were isolated and
      purified by various chromatographic techniques, and their structures were
      elucidated on the basis of physicochemical properties and spectral data. Three
      new alkaloids (compounds 1, 2, and 3) were obtained and identified as 9-((5
      methoxypyridin-2-yl)methyl)-9H-purin-6-amine (1), 4-(2-(2, 5-dioxopyrrolidin-1
      yl)ethyl)phenyl acetate (2), and N-(9-((5-methoxypyridin-2-yl)methyl)-9H-purin-6
      yl)acetamide (3). These compounds were evaluated for their cytotoxicity against
      human cervical cancer HeLa cells. Compounds 1 and 3 significantly inhibited the
      proliferation of HeLa cells with IC50 values being 3.02 +/- 0.54 and 7.16 +/-
      0.62 MUmol.L-1, respectively.

PMID- 29455730
TI  - Enhancement of oral bioavailability and immune response of Ginsenoside Rh2 by co
      administration with piperine.
AB  - Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides in Panax
      ginseng. However, the oral bioavailability of Rh2 is low, with P-glycoprotein (P
      gp) and CYP3A4 being reported to be the main factors. The purpose of the present
      study was to determine the enhancing effect of piperine on the oral
      bioavailability as well as bioactivity of Rh2. The inhibitory effect of piperine
      on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a
      recombinant CYP3A4 metabolic system, respectively. The pharmacokinetics of oral
      Rh2 (10 mg.kg-1) administered alone or in combination with piperine (10 and 20
      mg.kg-1) was performed in rats. The immune boosting effect of Rh2 was assessed in
      rats by measuring IL-12 level after treated by Rh2 alone or co-administered with
      piperine. The results indicated that piperine significantly increased the
      permeability of Rh2 and inhibited the metabolism of Rh2. The pharmacokinetic
      study results showed that the AUC of Rh2 was significantly increased in
      combination with piperine at high dose (20 mg.kg-1) when compared to the control
      group, with relative bioavailability of 196.8%. The increase of Rh2 exposure led
      to increased serum levels of IL-12. In conclusion, piperine may be used as a
      bioenhancer to improve pharmacological effect of Rh2 when given orally.

PMID- 29455731
TI  - Rapid screening and identification of sesquiterpene lactones in Kudiezi injection
      based on high-performance liquid chromatography coupled with linear ion trap
      orbitrap mass spectrometry.
AB  - Sesquiterpene lactones are considered as the major active compounds in Kudiezi
      injection in virtue of their special structures and activities. Herein, an
      analytical method was developed for rapid screening and identification of
      sesquiterpene lactones in Kudiezi injection using high-performance liquid
      chromatography coupled with linear ion trap-orbitrap mass spectrometry (HPLC-LTQ
      Orbitrap) in negative ion mode. First, two sesquiterpene lactone reference
      standards were analyzed to obtain their characteristic ESI-MS/MS fragmentation
      patterns. Second, based on extracted ion chromatography (EIC) data-mining method
      and characteristic fragmentation pathways analysis, sesquiterpene lactones in
      Kudiezi injection were rapidly screened and identified. Finally, an important
      parameter Clog P was adopted to discriminate the isomers of sesquiterpene
      lactones. As a result, 50 sesquiterpene lactones were characterized, including 9
      sesquiterpene lactone aglycones, 39 sesquiterpene lactone glycosides, and 2 amino
      acid-sesquiterpene lactone conjugates. Among them, 13 compounds were tentatively
      identified as new compounds. The results demonstrated that the established method
      would be a rapid, effective analytical tool for screening and identification of
      sesquiterpene lactones in the complex system of natural medicines.

PMID- 29455732
TI  - Morphological and chemical studies of artificial Andrographis paniculata
      polyploids.
AB  - Andrographis paniculata (Burm. f.) Nees (AP) is commonly used for the treatment
      of many infectious diseases and has been cultivated widely in Asian countries,
      and has been included in United States Pharmacopoeia as a dietary supplement, but
      the cultivars of A. paniculata are not abundant due to its self-pollinated. With
      the aims to enrich AP resources and provide materials for after breeding we
      explored the polyploidy induction. Different explants, colchicine concentration,
      and treatment time were tested. After identification by flow cytometry, eleven
      polyploid plants with different morphologic traits were obtained. The agronomic
      traits and andrographolide concentration of the polyploids were improved greatly.
      One of the polyploids (serial 3-7) was chosen for further study. The traits of
      the second and third generation polyploids (serial 3-7) were stable. Compared
      with the normal plants, the seeds (2nd generation) weight increased by 31%, and
      the andrographolide concentration of the leaves increased by 14% (2nd) and 28%
      (3rd). In conclusion, AP autopolyploids with different morphologic traits were
      established successfully for the first time, and the polyploids induction might
      be effective for crop improvement of AP.

PMID- 29455733
TI  - Taxus chinensis ameliorates diabetic nephropathy through down-regulating TGF
      beta1/Smad pathway.
AB  - Diabetic nephropathy (DN) is one of the common microvascular complications of
      diabetes mellitus. Renal fibrosis is closely related to the deterioration of
      renal function. The present study aimed to investigate protective effect of Taxus
      chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the
      underlying mechanism of action. The rat DN model was established via feeding high
      fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg.kg-1 body
      weight) intraperitoneally. The rats with blood glucose levels higher than 16.8
      mmol.L-1 were selected for experiments. The DN rats were treated with Taxus
      chinensis orally (0.32, 0.64, and 1.28 g.kg-1) once a day for 8 weeks. Taxus
      chinensis significantly improved the renal damage, which was indicated by the
      decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and
      blood urea nitrogen. Histopathological examination confirmed the protective
      effect of Taxus chinensis. The thickness of glomerular basement membrane was
      reduced, and proliferation of mesangial cells and podocytes cells and increase in
      mesangial matrix were attenuated. Further experiments showed that Taxus chinensis
      treatment down-regulated the expression of TGF-beta1 and alpha-SMA, inhibited
      phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus
      chinensis alleviated renal injuries in DN rats, which may be associated with
      suppressing TGF-beta1/Smad signaling pathway.

PMID- 29455734
TI  - Bamboo salt suppresses skin inflammation in mice with 2, 4-dinitrofluorobenzene
      induced atopic dermatitis.
AB  - Bamboo salt (BS) is a traditional Korean food, and has been reported to have anti
      cancer, anti-inflammatory, and anti-metastatic effects. However, the anti-atopic
      dermatitis (AD) activity of BS has not been described yet. In the present study,
      we examined the preventive effect of BS on AD. The effect of oral administration
      of BS was tested in a 2, 4-dinitrofluorobenzene (DNFB)-induced AD animal model,
      by histological analysis, enzyme-linked immunosorbent assay, reverse
      transcription-polymerase chain reaction, caspase-1 assay, and Western blotting
      analysis. BS administration reduced the total clinical severity and scratching
      frequencies, compared with the AD group. In the serum of DNFB-induced AD mice,
      the levels of IgE, histamine, thymic stromal lymphopoietin (TSLP), interleukin
      (IL)-5, and IL-13 were significantly reduced by BS treatment. BS significantly
      reduced the protein and mRNA expression of TSLP, IL-6, and tumor necrosis factor
      alpha in the AD skin lesions. BS markedly reduced the infiltration of
      inflammatory cells. Furthermore, the activation of caspase-1 was reduced by BS in
      the AD skin lesions. Our results suggested that BS should be considered as a
      candidate treatment for allergic inflammatory diseases including AD.

PMID- 29455735
TI  - Corrigendum to "Flow cytometric quantitation of platelet phagocytosis by
      monocytes using a pH-sensitive dye, pHrodo-SE" [Journal of Immunological Methods
      447 (2017) 57-64].
AB  - Antibody-mediated phagocytosis of platelets using a flow cytometric monocyte
      based phagocytosis assay (FMPA) has been shown to predict the outcome of platelet
      transfusion. The easy adherence between platelets and monocytes even in the
      absence of an antibody is regarded as one of limitations of the FMPA. To improve
      the FMPA for prediction of transfusion outcome, we used the pH-sensitive dye
      pHrodo succinimidyl ester (pHrodo-SE), which has weak fluorescence at neutral pH
      and has increased fluorescence intensity in low pH conditions such as in lysomes.
      Platelets stained with pHrodo-SE were sensitized with an HLA class I monoclonal
      antibody (w6/32 clone) or anti-HLA class I containing antisera. The platelets
      were incubated with monocyte-enriched mononuclear cells. Phagocytic activity was
      assessed by the percentage of monocytes that phagocytosed platelets.
      Sensitization of platelets with w6/32 significantly increased platelet
      phagocytosis by monocytes in dose- and time-dependent manners. Anti-HLA class I
      antibody-containing sera caused platelet phagocytosis in a cognate antigen
      antibody-dependent manner. There was a significant correlation (r=0.69, p<0.01)
      between phagocytic index and titer of HLA class I antibody measured by lymphocyte
      immunofluorescence test-flow cytometry. In addition, the phagocytic index
      obtained by FMPA with pHrodo-SE was significantly higher than that obtained by
      FMPA with the previously used dye, carboxyfluorescein diacetate succinimidyl
      ester, when platelets were sensitized by w6/32 and anti-HLA class I antibody
      containing sera. Because of the higher resolution and higher sensitivity than
      those of the previous method, the pHrodo-SE-based FMPA may be suitable for more
      precise quantitation of phagocytosis activity, which would enable qualitative
      evaluation of transfusion effectiveness.

PMID- 29455736
TI  - The impact of childhood neighborhood disadvantage on adult joblessness and
      income.
AB  - Research on residential inequality focuses heavily on adult economic outcomes as
      crucial components of the intergenerational transmission of poverty. Yet,
      empirical evidence on whether youth neighborhoods have a lasting impact on adult
      economic outcomes at the national level is scarce. Further, we know little about
      how youth neighborhood effects on adult economic outcomes manifest. This study
      uses 26 years (14 waves) of restricted panel data from the NLSY79 and the NLSY
      Children and Young Adults cohorts - data that have never been used to analyze
      long-term neighborhood effects - to examine whether youth neighborhood
      disadvantage impacts adult economic outcomes through sensitive years in
      childhood, teen socialization, duration effects, or cumulative effects. Sibling
      fixed effects models that net out unobserved effects of shared family
      characteristics suggest that youth neighborhood disadvantage increases
      joblessness and reduces income in adulthood. However, exposure across specific
      developmental stages of youth does not appear to act as a significant moderator
      while sustained exposure yields pernicious effects on adult economic outcomes.
      Moreover, these results are robust to alternative variable specifications and
      cousin fixed effects that net out potentially unobserved confounders, such as the
      inheritance of neighborhood disadvantage across three generations.

PMID- 29455737
TI  - Foreclosure migration and neighborhood outcomes: Moving toward segregation and
      disadvantage.
AB  - The US housing crisis during the late 2000s was arguably the most devastating
      residential disaster of the last century, sending millions of families into
      foreclosure and destroying billions in household wealth. An understudied aspect
      of the crisis was the spike in local migration that followed the foreclosure
      surge. In this paper, we assess the residential consequences of these moves, by
      exploring how foreclosure-induced migration affected the racial and socioeconomic
      composition of affected families' neighborhoods. To do so, we use the Panel Study
      of Income Dynamics to track foreclosure, migration, and neighborhood outcomes for
      samples of white, black, and Hispanic homeowners. Findings from our analysis show
      clearly that foreclosure was linked to migration to less white and more
      residentially disadvantaged neighborhoods, with foreclosed Hispanic householders,
      in particular, tending to move to poorer and more racially isolated
      neighborhoods.

PMID- 29455738
TI  - No experience required: Violent crime and anticipated, vicarious, and experienced
      racial discrimination.
AB  - There is a growing body of evidence linking racial discrimination and juvenile
      crime, and a number of theories explain this relationship. In this study, we draw
      on one popular approach, Agnew's general strain theory, and extend prior research
      by moving from a focus on experienced discrimination to consider two other forms,
      anticipated and vicarious discrimination. Using data on black, white, and
      Hispanic youth, from the Project on Human Development in Chicago Neighborhoods
      (PHDCN), we find that experienced, anticipated, and to a lesser extent, vicarious
      discrimination, significantly predict violent crime independent of a set of
      neighborhood, parental, and individual level controls, including prior violent
      offending. Additional analyses on the specific contexts of discrimination reveal
      that violence is associated with the anticipation of police discrimination. The
      effects tend to be larger for African American than Hispanic youth, but the
      differences are not statistically significant. These findings support the thesis
      that, like other strains, discrimination may not have to be experienced directly
      to influence offending.

PMID- 29455739
TI  - General population estimates of the association between college experience and
      the odds of forced intercourse.
AB  - Sexual assault on college campuses is a pervasive problem, recently receiving
      increased scientific and policy attention. However, the high focus on college
      student experience ignores general population prevalence, trends, and differences
      between those with college experience and those without. We analyze measures from
      the National Survey of Family Growth (NSFG) to provide a general population view
      of experiences with forced intercourse. Forced intercourse is a common experience
      in the U.S. population, has remained stable in recent years, and varies greatly
      by gender, age and race. The odds of forced intercourse are also significantly
      higher among those with less than four years of college. This ubiquitous public
      health problem is not limited to college campuses. Measures from the NSFG are an
      important resource for understanding population rates of (and trends in) forced
      intercourse, providing information to guide interventions and better target
      scientific investigation.

PMID- 29455740
TI  - Segregation paradox? School racial/ethnic and socioeconomic composition and
      racial/ethnic differences in engagement.
AB  - This study examines the associations between school racial/ethnic and
      socioeconomic composition and school engagement levels among Mexican-origin
      Latinos/as, African Americans, and non-Latino/a whites. Prior research suggests
      that whiter and more affluent schools should promote engagement, but some studies
      reveal paradoxes of school segregation whereby minority and socioeconomically
      disadvantaged students exhibit worse outcomes in schools with white and
      socioeconomically advantaged peers. Using data from the Education Longitudinal
      Study of 2002, this study examines the associations between the percent of non
      minority students in the school, average school socioeconomic status, and three
      engagement outcomes: Liking school, involvement in school-sponsored activities,
      and coursework engagement. The findings reveal an affective-behavioral trade-off
      for students in schools with higher proportions of white students. Students who
      attend whiter schools are less likely to report that they like school, but they
      are more engaged in coursework. This affective-behavioral paradox is not unique
      to any particular racial/ethnic group.

PMID- 29455741
TI  - Young immigrants' host country identification and their friendships with natives:
      Does relative group size matter?
AB  - Recent network research indicates that native youth prefer to befriend immigrants
      with stronger rather than weaker host country identification. Surprisingly,
      however, no respective preference of high-identifying immigrants for native
      friends has been found, and there is little evidence that friends influence
      immigrants' identification. Seeking to make sense of these unexpected findings,
      my aims are twofold: First, I reproduce an earlier study using three waves of
      newly collected network panel data. Second, going beyond a robustness test with
      better data, I suggest that relative group size within school accounts for
      earlier findings. I hypothesize that immigrants' host country identification only
      affects their own friendship choices in schools with high shares of immigrants,
      because only in those schools they can be picky about befriending natives.
      Stochastic actor-oriented models support this notion, pointing to an interplay of
      preferences and opportunities in shaping the relation between host country
      identification and interethnic friendships.

PMID- 29455743
TI  - Patience moderates the class cleavage in demand for redistribution.
AB  - Previous studies on class voting have yielded mixed results linking income and
      demand for redistribution. Why do some poor people oppose redistribution, while
      some rich people support it? This article argues that an individual's level of
      patience, an important personal characteristic that influences how people
      calculate immediate and distinct outcomes, may moderate the effect of class on
      redistributive preference. In a one-shot game, redistribution between the rich
      and the poor is zero sum. When people extend their time horizons, however, the
      poor see the possibility of upward mobility, while the rich emphasize future
      losses, such as unemployment and economic instability. Consistent with the
      hypotheses, analyses of the 2014 Cooperative Congressional Election Study and a
      representative Taiwanese dataset from 2016 reveal a clear class cleavage in
      demand for redistribution among impatient poor and rich respondents, but the
      cleavage between their patient counterparts diminished. This pattern of
      convergence extends previous studies on upward mobility and risk perception
      theory.

PMID- 29455742
TI  - Vocational education and employment over the life course using a new measure of
      occupational specificity.
AB  - Vocational education is seen as beneficial for the labor market allocation of
      young people. However, recent studies point to disadvantages later in the life
      course, where the specific skills that are obtained from vocational education
      decrease employability. This paper re-evaluates this hypothesis for the
      Netherlands with an improved measure for the vocational specificity of
      educational programs, utilizing both vertical (level) and horizontal (field)
      information on education. More specifically, we use a gradual measure for the
      linkage strength between education and occupation to predict employment over the
      life course. Using data from the national Dutch labor force surveys, we show that
      there is considerable heterogeneity in occupational specificity within the
      categories of vocational and general educational programs that is masked when
      using a dichotomous classification of general versus vocational education. In the
      life course analyses we find that the large early benefits of having vocational
      education disappear later in the career and turn into a small disadvantage before
      retirement.

PMID- 29455744
TI  - Neighbours matter: A nation-wide small-area assessment of environmental
      inequality in Germany.
AB  - This study investigates the presence of environmental inequality in Germany and
      analyses its spatial pattern on a very fine grained level. Using the 2011 German
      census and pollution measures of the E-PRTR, the study relies on nearly 100,000
      one squared km census cells over Germany. SLX and community-fixed SLX models
      incorporate spatial spillover-effects into the analysis to account for the
      spatial distribution of socio-demographic characteristics. Results reveal that
      the share of minorities within a census cell indeed positively correlates with
      the exposure to industrial pollution. Furthermore, spatial spillover effects are
      highly relevant: the characteristics of the neighbouring spatial units matter in
      predicting the amount of pollution. Especially within urban areas, clusters of
      high minority neighbourhoods are affected by high levels of environmental
      pollution. This highlights the importance of spatial clustering processes in
      environmental inequality research.

PMID- 29455745
TI  - Identifying diverse life transition patterns from adolescence to young adulthood:
      The influence of early socioeconomic context.
AB  - The purposes of the present study are to investigate: (1) the heterogeneity in
      life transition patterns of youth from adolescence to young adulthood (ages 18
      30) involving the timing and sequence of four transition events (college
      graduation, full-time employment, marriage, and parenthood), (2) the influence of
      early socioeconomic adversity on life transition patterns from adolescence to
      young adulthood, and (3) the influence of gender and race/ethnicity on these
      transition patterns. Using a multivariate discrete-time mixture survival model
      with a sample of 14,503 adolescents from the National Longitudinal Study of
      Adolescent to Adult Health (Add Health), the study identified four life
      transition patterns and found that early socioeconomic adversity shapes disrupted
      life transition patterns from adolescence to young adulthood. Gender and
      race/ethnicity differences are discussed. These results highlight the need for
      prevention and intervention programs that selectively target at-risk youth
      beginning in adolescence and continuing through subsequent transition periods.

PMID- 29455746
TI  - Today's decisions, Tomorrow's outcomes: Does self-control explain the educational
      smoking gradient?
AB  - People with more education tend to have relatively healthy lifestyles. Among
      other things, they smoke less than those with less education. This link between
      education and smoking (known as the "educational gradient") is frequently
      interpreted as causal: many researchers argue that education develops skills,
      habits, and preferences that discourage smoking and other unhealthy behaviors.
      However, an alternative possibility is that these skills, habits, and preferences
      develop early in life and determine the likelihood of both attaining a high level
      of education and avoiding smoking. I test the latter possibility using data from
      the Longitudinal Study of Adolescent to Adult Health (Add Health). In particular,
      I assess the degree to which indicators of self-control in adolescence explain
      the association between educational attainment and smoking in adulthood. Results
      from a series of regression-based tests indicate that self-control is a
      significant predictor of both outcomes, even when controlling for a host of other
      risk factors. However, it does not appear to explain the educational gradient.

PMID- 29455747
TI  - Intergenerational social mobility and religious ecology: Disaggregating the
      conservative Protestant bloc.
AB  - We extend research on the effects of religious ecologies by examining the role of
      religious ecologies in intergenerational socioeconomic mobility. We do so first
      by providing a theoretical framework addressing the diverse cultural influences
      of religious traditions and their impact on intergenerational mobility. We argue
      that certain otherworldly orientations among conservative Protestants suppress
      mechanisms of upward mobility, and that there are meaningful distinctions between
      sub-groups of conservative Protestants (evangelicals, fundamentalists, and
      Pentecostals). An analysis of county-level data from the recently released
      Equality of Opportunity Project and the Churches and Church Membership Survey is
      used to empirically examine the relationship between religious ecologies and
      intergenerational mobility. Findings suggest distinct effects of different
      religious groups on intergenerational mobility. These results demonstrate the
      importance of accounting for the ecological impact of religion on social mobility
      in the United States and challenge the conceptualization of conservative
      Protestants as a monolithic group.

PMID- 29455748
TI  - Cross-national variation in the social origins and religious consequences of
      religious non-affiliation.
AB  - I argue that the social implications of religious non-affiliation vary across
      cultural contexts, leading to differences across nations in both who is likely to
      be unaffiliated and the religious consequences of such non-affiliation. I test
      these propositions by examining cross-national variation in associations with non
      affiliation using multilevel models and cross-sectional survey data from almost
      70,000 respondents in 52 nations. The results indicate that: 1) both individual
      characteristics (gender, age, and marital status) and nation-level attributes
      (GDP, communism, and regulation of religion) strongly predict religious non
      affiliation; 2) differences in non-affiliation by individual-level attributes
      women vs. men, old vs. young, and married vs. single-are greatest in nations with
      low levels of religious regulation and high levels of economic development; and
      3) the effect of religious non-affiliation on religiosity varies considerably by
      the political and religious context, and to a lesser extent by the level of
      economic development in each nation. These results highlight cultural variation
      in what it means to be religiously unaffiliated.

PMID- 29455749
TI  - Does social insurance enrollment improve citizen assessment of local government
      performance? Evidence from China.
AB  - Although many studies claim that social policies are "carrots" that authoritarian
      leaders use to garner public support, the assumption that social benefits can
      boost public support of government has been rarely tested empirically, especially
      at the local levels. This article investigates the effects of social insurance
      enrollment on citizens' assessment of local government performance using data
      from the 2010 China Family Panel Study. We use propensity score matching to
      reduce selection bias and ordered probit regressions with fixed effects to
      examine these possible effects. We find that social insurance enrollment had a
      significant positive effect on rural citizens' assessment of government
      performance, but this effect did not exist for their urban and migrant peers.
      This discrepancy could be largely due to the groups' different expectations for
      government redistribution and their distinct experiences of China's social
      welfare reform. We conclude that the Chinese authoritarian government has
      achieved partial success in its attempt to use social policies to maintain
      popular support.

PMID- 29455751
TI  - Varieties of political support in emerging democracies: A cross-national
      analysis.
AB  - Political support is a multidimensional construct encompassing evaluations of
      political leaders and institutions (specific support) as well as adherence to
      basic regime principles (diffuse support). Scholars have traditionally assumed
      that diffuse and specific support are driven by different forces and evolve
      largely independently. Prior empirical work, however, has struggled to untangle
      the two support dimensions and focused predominantly on cross-national
      differences, ignoring their dynamics. This paper develops an analytical and
      empirical approach to examine the levels and dynamic interplay of both support
      dimensions and estimate their determinants, applying it to South American
      democracies between 1996 and 2015. Contrary to received wisdom, we show that both
      dimensions are quite volatile and closely linked in this region. In particular,
      negative economic shocks not only undermine support for government actors, but
      also fuel democratic disenchantment. Nonetheless, while regime support is rather
      fickle in South America, it can be ultimately resistant to performance
      fluctuations.

PMID- 29455750
TI  - Trigger events and poverty transitions among young adults in Finland after
      leaving the parental home.
AB  - Studies have shown that leaving the parental home is associated with an increase
      in the risk of poverty. However, less is known about poverty dynamics after
      leaving the nest. Based on Finnish population register data, this research
      answers the question of how employment and demographic events affect poverty
      entries and exits among 18- to 24-year-olds in Finland. The follow-up of
      individuals starts when young adults move away from the parental home. In
      addition to descriptive methods, discrete-time event-history models are
      estimated. This study illustrates that changes in employment are typical and are,
      therefore, often associated with poverty transitions among young adults. Although
      demographic events are less common, when experienced, they often lead to poverty
      transitions. This study found that the effects of demographic events vary by
      gender. This study also illustrates that a move back to the parental home is more
      likely for some poor population subgroups than for others.

PMID- 29455752
TI  - Imagining class: A study into material social class position, subjective
      identification, and voting behavior across Europe.
AB  - The traditional approach to class voting has largely ignored the question whether
      material class positions coincide with subjective class identification. Following
      Sosnaud et al. (2013), this study evaluates party preferences when Europeans'
      material and subjective social class do not coincide. Seminal studies on voting
      behavior have suggested that members of lower classes are more likely to vote for
      the economic left and cultural right and that higher classes demonstrate the
      opposite pattern. Yet, these studies have on the one hand overlooked the
      possibility that there is a mismatch between the material class people can be
      classified in and the class they think they are part of, and on the other hand
      the consequences of this discordant class identification on voting behavior.
      Analyzing the 2009 wave of the European Elections Study, we find that the
      majority of the Europeans discordantly identify with the middle class, whereas
      only a minority of the lower and higher classes concordantly identify with their
      material social class. Further, material class only seems to predict economic
      voting behavior when it coincides with subjective class; for instance,
      individuals who have an inflated class identification are more likely to vote for
      the economic left, even when they materially can be classified as middle or high
      class. We conclude this paper with a discussion on scholarly debates concerning
      class and politics.

PMID- 29455754
TI  - Are Concussion Laws Making Youth Athletes Safer?

PMID- 29455753
TI  - Varieties of indebtedness: Financialization and mortgage market institutions in
      Europe.
AB  - During the global housing boom that preceded the 2007-9 financial crisis,
      household debt increased substantially in many European countries, posing a
      challenge for literature on financialization and the institutional heterogeneity
      of mortgage markets. This paper examines recent institutional shifts in European
      mortgage markets and specifies three analytically distinct models of debt
      accumulation: inclusion, extension and intensity. While existing research has
      emphasized inclusion (access to homeownership), we show that financial
      intensification is an important determinant of cross-national variation in debt.
      We assess the variation in financial intensity in six European countries (France,
      Germany, Italy, the Netherlands, Portugal and Spain) using household-level survey
      data. Our results show that inclusion and expansion explain only part of the
      cross-national variation in mortgage debt to income ratios. Furthermore,
      household financial behavior is consistent with the financial intensity model,
      and variation in the degree of financial intensification explains a substantial
      portion of the cross-national difference in debt levels.

PMID- 29455755
TI  - Quality Measurement Is Key to Improving Family Planning Services and Outcomes for
      Adolescents in Low- and Middle-Income Countries.

PMID- 29455756
TI  - A Randomized Trial of Weight Change in a National Home Visiting Program.
AB  - INTRODUCTION: Clinical trials have demonstrated significant impact in reducing
      weight and incidence of type 2 diabetes mellitus. However, the intensity of these
      trials limits their scalability to real world settings. The purpose of this study
      was to embed a lifestyle intervention for overweight and obese mothers within the
      routine practice of a parent education, home visiting organization. DESIGN:
      Pragmatic trial that used a stratified random design. SETTING/PARTICIPANTS:
      Overweight or obese mothers of preschool children located across St. Louis,
      Missouri, enrolled in Parents As Teachers, a home visiting organization reaching
      women and children nationwide. INTERVENTION: A lifestyle intervention derived
      from the Diabetes Prevention Program was embedded within Parents As Teachers
      entitled Healthy Eating and Active Living Taught at Home (HEALTH). MAIN OUTCOME
      MEASURES: Outcomes included the proportion of women that achieved 5% weight loss
      at 24 months and improvements in clinical and behavioral outcomes at 12 and 24
      months. Participants were enrolled from 2012 to 2014 and data analysis began in
      2016. RESULTS: Women in the usual care versus intervention group were
      significantly less likely to achieve 5% weight loss at 24 months (11% vs 26%,
      p=0.01). At 12 months, there was a 2.8-kg difference in weight between groups
      (p=0.0006), and by 24 months a 4.7-kg difference in weight (3.2 [SD=7.6] kg vs 
      1.5 [SD=8.3] kg, p=0.002); group differences in waist circumference were also
      evident by 12 months (2.1 [SD=8.4] cm vs -0.7 [SD=9.8] cm, p=0.04) and 24 months
      (3.8 [SD=10.6] cm vs -2.5 [SD=9.1] cm, p=0.005), as were improvements in
      behavioral outcomes. There was no difference in blood pressure between groups.
      CONCLUSIONS: HEALTH achieved modest but clinically significant weight loss
      outcomes, and reduced weight gain in mothers of young children. The scalability
      of this embedded intervention offers the potential to reach mothers in Parents As
      Teachers programs nationally. TRIAL REGISTRATION: This study is registered at
      www.clinicaltrials.gov NCT01567033.

PMID- 29455757
TI  - Federal Nutrition Program Revisions Impact Low-income Households' Food Purchases.
AB  - INTRODUCTION: The Special Supplemental Nutrition Program for Women, Infants and
      Children (WIC) required major revisions to food packages in 2009; effects on
      nationwide low-income household purchases remain unexamined. METHODS: This study
      examines associations between WIC revisions and nutritional profiles of packaged
      food purchases from 2008 to 2014 among 4,537 low-income households with
      preschoolers in the U.S. (WIC participating versus nonparticipating) utilizing
      Nielsen Homescan Consumer Panel data. Overall nutrients purchased (e.g.,
      calories, sugar, fat), amounts of select food groups with nutritional attributes
      that are encouraged (e.g., whole grains, fruits and vegetables) or discouraged
      (e.g., sugar-sweetened beverages, candy) consistent with dietary guidance,
      composition of purchases by degree of processing (less, moderate, or high), and
      convenience (requires preparation, ready to heat, or ready to eat) were measured.
      Data analysis was performed in 2016. Longitudinal random-effects model adjusted
      outcomes controlling for household composition, education, race/ethnicity of the
      head of the household, county quarterly unemployment rates, and seasonality are
      presented. RESULTS: Among WIC households, significant decreases in purchases of
      calories (-11%), sodium (-12%), total fat (-10%), and sugar (-15%) occurred,
      alongside decreases in purchases of refined grains, grain-based desserts, higher
      fat milks, and sugar-sweetened beverages, and increases in purchases of
      fruits/vegetables with no added sugar/fats/salt. Income-eligible nonparticipating
      households had similar, but less pronounced, reductions. Changes were gradual and
      increased over time. CONCLUSIONS: WIC food package revisions appear associated
      with improved nutritional profiles of food purchases among WIC participating
      households compared with low-income nonparticipating households. These package
      revisions may encourage WIC families to make healthier choices among their
      overall packaged food purchases.

PMID- 29455758
TI  - Research on Childhood Obesity: Building the Foundation for a Healthier Future.

PMID- 29455759
TI  - A National Collaborative for Building the Field of Childhood Obesity Research.
AB  - Rising rates of childhood obesity over the past 2 decades have spurred a number
      of public- and private-sector initiatives aimed at halting or even reversing this
      trend. Recognizing common interests in this issue, the Centers for Disease
      Control and Prevention, NIH, and the Robert Wood Johnson Foundation began
      conversations about creating a formal collaboration aimed at accelerating efforts
      to address childhood obesity by coordinating research agendas and providing
      support for evidence-building activities. The National Collaborative on Childhood
      Obesity Research (NCCOR) was launched in February 2009, and the U.S. Department
      of Agriculture joined in 2010. Using the model provided by other previously
      successful collaborations, such as the Youth Tobacco Cessation Collaborative,
      NCCOR has emphasized several principles suggested by Petrovich as key elements
      for successful partnerships: (1) delineate a common purpose by identifying key
      knowledge gaps in the field; (2) create a shared identity around that common
      purpose; (3) develop structures for democratic and respectful collaboration so as
      to strategically coordinate efforts for maximum national impact; (4) identify
      effective leaders capable of articulating challenges in the field and inspiring a
      commitment of minds and the resolve to address identified needs; (5) facilitate
      continuous knowledge exchange and synthesis to keep the field informed; and (6)
      support assessment of progress and feedback loops for ensuring continual
      progress. This paper examines how NCCOR has used these principles to help build
      the field of research, evaluation, and surveillance for childhood obesity
      prevention and management.

PMID- 29455760
TI  - Developing a Partnership for Change: The National Collaborative on Childhood
      Obesity Research.
AB  - Rising obesity rates in the U.S. over the past several decades, particularly
      among children and adolescents, led to an increased focus on research addressing
      obesity prevention and public- and private-sector initiatives on healthy eating
      and physical activity. Groups conducting prevention initiatives recognized that
      their ability to achieve and sustain cross-sector environmental, policy, and
      systems-level solutions was hampered by limited evidence in those areas. In 2007,
      the Centers for Disease Control and Prevention, NIH, and the Robert Wood Johnson
      Foundation began to discuss forming a partnership that could accelerate progress
      to prevent childhood obesity by coordinating research and evaluation agendas and
      collaboratively building an evidence base. This paper describes the formation,
      structure, and operations of the National Collaborative on Childhood Obesity
      Research, the resulting partnership between the Centers for Disease Control and
      Prevention, NIH, the Robert Wood Johnson Foundation, and since 2010, the U.S.
      Department of Agriculture. It includes a discussion of lessons learned from, and
      benefits of, this collaborative model.

PMID- 29455761
TI  - The Value of the National Collaborative on Childhood Obesity Research: Past,
      Present, and Future.

PMID- 29455762
TI  - BVS, RDN, IABP: The Afghanistan of interventional cardiology trials.
AB  - In the field of medicine and cardiology newer therapy and devices have been
      launched with a huge promise and a lot of hype. Unfortunately, over the course of
      time, a good many of them like biovascular scaffold, renal denervation and intra
      aortic balloon pump have failed to live up to their initial promise so much so
      that some of them have been withdrawn. The reason for this downfall may be
      multifold from incomplete understanding of the patho-physiology of disease,
      incomplete understanding of mechanism of action of the therapy, in-appropriate
      application in clinical practice, in-efficient therapy development related to
      flawed trial design, regulatory impediments placed on the trials or deficits in
      application of scientific techniques. Here-in we investigate the specific reason
      for failure for some of these therapies and attempt to suggest a way forward.

PMID- 29455763
TI  - Low major adverse cardiac event rates following bioresorbable vascular scaffold
      implantation: Impact of implantation technique on treatment outcomes.
AB  - BACKGROUND AND OBJECTIVE: Studies conducted across the world have reported that
      the rates of major adverse cardiac events (MACE) following the use of
      bioresorbable vascular scaffolds (BVS) are comparable to that noted with
      traditional drug eluting stents (DES). However, there is limited data on the
      immediate and medium-term clinical outcomes following the use of the Absorb BVS
      (Abbott Vascular, Santa Clara, SA) in the Indian context. This study was
      conducted to determine real-world evidence on the immediate and medium-term
      clinical outcomes in all patients undergoing percutaneous coronary intervention
      (PCI) with the Absorb BVS. METHODS: Data of all patients who were treated with
      Absorb BVS at our center were evaluated. Between December 2012 and October 2016,
      142 patients underwent PCI with BVS. The MACE rates during hospitalization, at
      30days, 3 months, 6 months after PCI, and every 6 months thereafter were the
      primary endpoints evaluated with median follow up of 13 months. RESULTS: Mean age
      of the study participants was 53.7+/-11.8years. Intravascular ultrasound imaging
      was performed in 15.34% of patients. Predilatation and postdilatation were
      performed in 81.8% and 84.6% of scaffolds, respectively. There were no episodes
      of MACE during hospitalization. However, 1 BVS-related MACE was observed at the 1
      month (0.7%) as well as at the >=12 month (0.8%) follow up visits. At the 6- and
      12-month follow up visits, 2 (1.5%) and 3 (2.5%) non-BVS-related MACEs,
      respectively, were recorded. CONCLUSION: The use of Absorb BVS in this real-world
      experience was associated with very good immediate and medium-term clinical
      outcomes.

PMID- 29455765
TI  - Increasing cardiopulmonary aerobic activity improves motor cognitive response
      time: An inference from preliminary one-group pretest-posttest quasi-experimental
      study.
AB  - Motor cognitive response time (MCRT) is the time elapsed between presenting a
      stimulus and the time taken by that individual to respond to that stimulus
      through a motor performance. After completing aerobic exercise, there are various
      changes that takes place, one of which might be change in cognitive function.
      Whether cardiopulmonary aerobic activity/capacity has an impact on MCRT is not
      explored yet.

PMID- 29455764
TI  - Management protocols for chronic heart failure in India.
AB  - Heart failure is a common clinical syndrome and a global health priority. The
      burden of heart failure is increasing at an alarming rate worldwide as well as in
      India. Heart failure not only increases the risk of mortality, morbidity and
      worsens the patient's quality of life, but also puts a huge burden on the overall
      healthcare system. The management of heart failure has evolved over the years
      with the advent of new drugs and devices. This document has been developed with
      an objective to provide standard management guidance and simple heart failure
      algorithms to aid Indian clinicians in their daily practice. It would also inform
      the clinicians on the latest evidence in heart failure and provide guidance to
      recognize and diagnose chronic heart failure early and optimize management.

PMID- 29455766
TI  - Letter to the editor.

PMID- 29455767
TI  - Problems encountered in retrograde recanalization of coronary chronic total
      occlusion: Should we lock the backdoor in 2018?

PMID- 29455768
TI  - Utility of OCT In a patient with chronic stable angina- "All that is seen using
      dye is not true".

PMID- 29455769
TI  - Prevention of sudden cardiac death in athletes, sportspersons and marathoners in
      India.
AB  - The annual incidence of sudden cardiac death (SCD) in athletes is significantly
      lower than the general population. However, when SCD occurs in an athlete during
      sporting event or training, it sends shockwaves in the society and raises
      questions about cardiovascular effects of sports and exercise. This document
      reviews the causes and mechanism of SCD in sports and exercise in young and older
      athletes. In the Indian context, we suggest a 'pre-participation screening' of
      young and older athletes and consider a 'supervised, graded exercise regime' for
      the uninitiated, older sports participant. Finally, the document proposes medical
      infrastructure required to successfully revive a victim of sudden cardiac arrest
      during a sporting event.

PMID- 29455770
TI  - Use of coronary hardware in peripheral vascular interventions: Necessity fostered
      ingenuity-Is it solution enough?
AB  - In third world countries like India, where there is a paucity of dedicated
      interventional radiologists and training fellowships in peripheral interventions,
      it is the onus of the cardiologist to perform peripheral interventions. This
      coupled with logistic constraints of unavailability of medical insurance for
      majority of the population, makes it necessary to modify coronary hardware for
      use in peripheral interventions. Here, we discuss the modifications and
      simplifications performed to ensure optimal quality of clinical outcomes.

PMID- 29455771
TI  - Angiographic predictors of success in antegrade approach of Chronic Total
      Occlusion interventions in a South Indian population in the contemporary era.
AB  - : Chronic Total Occlusion (CTO) intervention is a challenging area in
      interventional cardiology. Presently about 70% of CTO interventions are
      successful. MATERIALS AND METHODS: This was a single center prospective study of
      a cohort of all patients undergoing percutaneous coronary intervention (PCI) as
      elective or adhoc procedure for CTO from August 2014 to June 2015. Only antegrade
      CTO interventions were included. In all patients the following data were
      recorded. RESULTS: A total of 210 (8.9% of total PCI (2353) during the study
      period) CTO patients were followed up. The mean age was 56.54+/-8.9. In the study
      sixty nine patients (32.9%) presented with chronic stable angina and rest of the
      patients had history of acute coronary syndrome of which 22.9% (n=48) had
      unstable angina (UA) or non ST elevation myocardial infarction (NSTEMI) and 44.2%
      (n=93) had ST Elevation Myocardial Infarction (STEMI). In those with history of
      ACS, 64.78% (n=92) had ACS during the previous year and remaining 35.22% (n=49)
      had ACS prior to that. Single vessel CTO was seen in 89.5% (n=188) and two vessel
      CTO in 10.5% (n=22). LAD was involved in 36.7% (n=77), RCA in 48.1% (n=101), and
      LCX in 15.2% (n=32). Procedural success in the first attempt was 68.1% (n=143),
      which increased to 71.42% (n=150) after the second attempt. CTO interventions
      were more frequently successful when the calcium was absent or minimal (p-0.05),
      CTO length was <10mm (p<0.01) and good distal reformation (p<0.01).

PMID- 29455772
TI  - Prenatal diagnosis of congenital heart disease: A review of current knowledge.
AB  - This article reviews important features to improve the diagnosis of congenital
      heart disease (CHD) by applying ultrasound in prenatal cardiac screening. As low
      and high-risk pregnancies for CHD are subject to routine obstetric ultrasound,
      the diagnosis of structural heart defects represents a challenge that involves a
      team of specialists and subspecialists on fetal ultrasonography. In this review,
      the images highlight normal anatomy of the heart as well as pathologic cases
      consistent with cardiac malposition and isomerism, septal defects, pulmonary
      stenosis/atresia, aortic malformations, hypoplastic left ventricle, conotruncal
      anomalies, tricuspid dysplasia, and Ebstein's anomaly, and univentricular heart,
      among other congenital cardiovascular defects. Anatomical details of most CHD in
      fetuses were provided by two-dimensional (2D) ultrasound with higher quality
      imaging, enhancing diagnostic accuracy in a variety of CHD. Moreover, the
      accuracy of the cardiac defects in obstetrics ultrasound improves the outcome of
      most CHD, providing planned delivery, aided genetic counseling, and perinatal
      management.

PMID- 29455773
TI  - Takotsubo syndrome.
AB  - Takotsubo syndrome is a reversible acute heart failure frequently precipitated by
      an emotional or physical stress. The clinical presentation resembles acute
      coronary syndrome. Pathogenesis is complex and may involve brain-heart axis and
      neuro-hormonal stunning of the myocardium. Coronary angiography reveals normal
      epicardial arteries with no obstruction or spasm. NT-ProBNP maybe remarkably
      elevated. Regional wall motion akinesia (RWMA) of left ventricle extends beyond
      the territory of one coronary artery. Reduced left ventricle ejection fraction
      (LVEF) and RWMA recover in 6-12 weeks. Prognosis is generally good. Recent meta
      analysis shows in-hospital mortality of 1-4.5% and recurrence rate of 5-10%
      during five year follow-up.

PMID- 29455774
TI  - Metformin in heart failure patients.
AB  - The use of metformin was considered a contraindication in heart failure patients
      because of the potential risk of lactic acidosis; however, more recent evidence
      has shown that this should no longer be the case. We reviewed the current
      literature and the recent guideline to correct the misconception.

PMID- 29455775
TI  - Stress cardiomyopathy of the critically ill: Spectrum of secondary, global,
      probable and subclinical forms.
AB  - Stress cardiomyopathy (SC) typically presents as potential acute coronary
      syndrome (ACS) in previously healthy people. While there may be physical or
      mental stressors, the initial symptom is usually chest pain. This form conforms
      to the published Mayo diagnostic criteria, is well reported and as the
      presentation is initially cardiac, is considered primary SC. Increasingly we see
      SC develop several days into the hospitalization secondary to medical or surgical
      critical illness. This condition is more complex, presents atypically, is not
      easy to recognize and carries a much worse prognosis. Label of Secondary SC is
      appropriate as it manifests in sicker hospitalized patients with numerous
      comorbidities. We review the limited but provocative literature pertinent to SC
      in the critically ill and describe important clues to identify global,
      subclinical and probable forms of SC. We illustrate the several unique clinical
      features, demographic differences and propose a diagnostic algorithm to optimize
      cardiac care in the critically ill.

PMID- 29455776
TI  - Confronting system barriers for ST- elevation MI in low and middle income
      countries with a focus on India.
AB  - Our previous research found seven specific factors that cause system delays in ST
      elevation Myocardial infarction management in developing countries. These delays,
      in conjunction with a lack of organized STEMI systems of care, result in
      inefficient processes to treat AMI in developing countries. In our present
      opinion paper, we have specifically explored the three most pertinent causes that
      afflict the seven specific factors responsible for system delays. In doing so, we
      incorporated a unique strategy of global STEMI expertise. With this methodology,
      the recommendations were provided by expert Indian cardiologist and final
      guidelines were drafted after comprehensive discussions by the entire group of
      submitting authors. We expect these recommendations to be utilitarian in
      improving STEMI care in developing countries.

PMID- 29455778
TI  - Predictors of obstructive coronary artery disease in women.

PMID- 29455779
TI  - Obesity in adult asian indians- the ideal BMI cut-off.

PMID- 29455777
TI  - Palliative treatment of coronary "atherosclerotic cancer" by drug-eluting or bare
      metal stents: From oculo-stenotic reflex period to age of precision medicine.
AB  - Medications and treatments are said to have a palliative effect if they relieve
      symptoms without having a curative effect on the underlying disease such as
      atherosclerosis or cancer. Some authors speculated that atherosclerotic coronary
      artery disease (CAD) could be considered a "cancer of the coronary arterial
      wall". Although the percutaneous coronary intervention (PCI) has proven to be
      effective in decreasing mortality rates among patients with acute coronary
      syndromes, the previous meta-analyses of PCI versus optimal medical therapy for
      stable CAD have not been able to demonstrate a reduction in major adverse cardiac
      outcomes. However, few cardiologists discussed the evidence-based benefits of
      angiogram and PCI for stable CAD, and some implicitly or explicitly overstated
      the benefits. Recently, the precision medicine is defined as an evidence-based
      approach that uses innovative tools and biological and data science to customize
      disease prevention, detection, and treatment, and improve the effectiveness and
      quality of patient care. Providing patients with accurate and complete
      information appears to be an effective way to combat the reliance on the
      oculostenotic reflex. The foundation of precision medicine is the ability to
      tailor therapy based upon the expected risks and benefits of treatment for each
      individual patient. As said by Doctor William Osler, "The good physician treats
      the disease; the great physician treats the patient who has the disease."

PMID- 29455780
TI  - Soluble ST2 biomarker and reverse remodelling in patients with systolic heart
      failure.

PMID- 29455781
TI  - The truth about artificial sweeteners - Are they good for diabetics?
AB  - Artificial sweeteners are thought to be beneficial for diabetics or obese where
      refined sugar can be a problem. These low-calorie sweeteners are seemingly safe
      to use, provide sweetness without calories, and provide a choice of sweet foods
      to those who otherwise cannot partake them (refined sugars). However, while
      artificial sweeteners may indeed restrict calories most of them have no
      beneficial effects on control of diabetes mellitus; rather possibly increase its
      risk. Additionally, there could be some other safety concerns possibly risk of
      cancer.

PMID- 29455782
TI  - Predictors of major adverse cardiac events following elective stenting of large
      coronary arteries.
AB  - OBJECTIVE: Diameter of the affected coronary artery is an important predictor of
      restenosis and need for revascularization. In the present study, we investigated
      the frequency and potential risk factors for major adverse cardiac events
      following elective percutaneous coronary intervention (PCI) and stenting of large
      coronary arteries. METHODS: We reviewed the data of elective candidates of PCI on
      a large coronary artery who presented to our center. Demographic, clinical,
      angiographic and follow-up data of the eligible patients were retrieved from our
      databank. The study characteristics were then compared between the patients with
      and without MACE in order to find out the probable risk factors for MACE in
      patients with large stent diameter. RESULTS: Data of 3043 patients who underwent
      single vessel elective PCI with a stent diameter of >=3.5mm was reviewed. During
      a median follow up period of 14 months, 64 (2.1%) patients had MACE. TVR was the
      most common type of MACE that was observed in 29 patients, while 5 patients had
      cardiac death. Higher serum levels of creatinine, history of cerebrovascular
      accident (CVA), and use of a drug eluting stent (DES) were significantly
      associated with MACE. In the multivariate model, history of CVA (odds ratio=5.23,
      P=0.030) and use of DES (odds ratio=0.048, P=0.011) were the independent
      predictors of MACE in patients underwent large coronary artery stenting.
      CONCLUSION: This study showed that prior CVA and the use of BMS were the
      potential risk factors for MACE in patients who were stented on their large
      coronary arteries.

PMID- 29455783
TI  - Simplified percutaneous closure of patent foramen ovale and atrial septal defect
      with use of plain fluoroscopy: Single operator experience in 110 consecutive
      patients.
AB  - OBJECTIVE: Percutaneous closure of patent foramen ovale (PFO) and atrial septal
      defect (ASD) is routinely performed under general anesthesia or deep sedation and
      use of transesophageal (TEE) or intracardiac echocardiography, incurring longer
      duration and higher cost. We have used a simplified, economical, fluoroscopy-only
      guided approach with local anesthesia, and herein report our data. METHODS: The
      study includes 112 procedures in 110 patients with PFO (n=75) or ASD (n=35), with
      use of an Amplatzer occluder, heparin and prophylactic antibiotics. Balloon
      sizing guided ASD-device selection. All patients received aspirin and clopidogrel
      for 6 months, when they all underwent TEE. RESULTS: All PFOs but one (98.7%) and
      all (100%) ASDs were successfully closed with only one complication (local
      pseudoaneurysm). At the 6-month TEE, there was no residual shunt in PFO patients,
      but 2 ASD patients had residual shunts. During long-term (4.3-year) follow-up, no
      stroke recurrence in PFO patients, and no other problems were encountered. Among
      54 patients suffering from migraine, symptom relief or resolution was reported by
      45 (83.3%) patients. CONCLUSION: Percutaneous placement of an Amplatzer occluder
      was safe and effective with use of local anesthesia and fluoroscopy alone. There
      were no recurrent strokes over >4 years. Migraine relief was reported by >80% of
      patients.

PMID- 29455784
TI  - Complications after elective percutaneous coronary interventions: A comparison
      between public and private hospitals.
AB  - OBJECTIVE: Complications after percutaneous coronary interventions (PCI) are
      associated with significant morbidity and mortality, although institutional
      discrepancies can occur when public and private hospitals coexist within the
      healthcare system. The aim of this study was to compare the in-hospital
      complication rates and mortality in addition to long-term survival following
      elective PCI in two reference public and private cardiology hospitals in Rio de
      Janeiro, Brazil. METHODS: From January 1st 2013 to December 31st 2014, a total of
      440 procedures were identified in both hospitals (public: 328 vs. private: 112)
      and retrospectively analyzed by chart review. RESULTS: There were no significant
      differences between the two hospitals regarding the total number of procedures
      with at least one complication (public: 23.8 vs. private: 17.9%, p=0.2) or in
      hospital mortality rates (public: 0.6% vs. private: 0%, p=0.5). Post-procedural
      renal insufficiency was more frequent in the private hospital, whereas coronary
      related complications were more prevalent in the public hospital. After a mean
      follow up of 30.3 months (SD+/-9.2), the survival rate was also similar.
      CONCLUSIONS: Clinical complications after elective PCI are common both in public
      and private hospitals. Meticulous pre-procedural clinical assessment and patient
      selection as well as adherence to guideline-based practices could minimize the
      risk of PCI-related adverse events.

PMID- 29455785
TI  - Esophageal positions relative to the left atrium; data from 293 patients before
      catheter ablation of atrial fibrillation.
AB  - AIMS: Three-dimensional rotational angiography (3DRA) of the left atrium (LA) and
      the esophagus is a simple and safe method for analyzing the relationship between
      the esophagus and the LA during catheter ablation of atrial fibrillation. The
      purpose of this study is to describe the location of the esophagus relative to
      the LA and mobility of the esophagus during ablation procedure. METHODS: From
      3/2011 to 9/2015, 3DRA of the LA and esophagus was performed in 326 patients
      before catheter ablation of atrial fibrillation. 3DRAwas performed with
      visualization of the esophagus via peroral administration of a contrast agent.
      The positions of the esophagus were determined at the beginning of the procedure,
      for part of patients also at the end of procedure with contrast esophagography.
      RESULTS: The most frequent position is behind the center of the LA (91 pts.,
      31.9%) The least frequent position is behind the right pulmonary veins (27 pts.,
      9.4%). The average shift of the esophagus position was 3.36+/-2.15mm, 3.59+/
      2.37mm and 3.67+/-3.23mm for superior, middle and inferior segment resp.
      CONCLUSIONS: The position of the esophagus to the LA is highly variable. The most
      common position of the esophagus relative to the LA is behind the middle and left
      part of the posterior wall of the LA. The least frequently observed position is
      behind the right pulmonary veins. No significant position change of esophagus
      motion from before to after the ablation procedure in the majority (>=95%) of the
      patients was observed.

PMID- 29455786
TI  - Examination of the appropriate timing of reperfusion therapy for recent
      myocardial infarction: a Japanese single-center retrospective study.
AB  - BACKGROUND: The various guidelines clearly mention the treatment strategies for
      in patient of acute myocardial infarction (MI) presenting more than 24h from
      symptom onset (recent myocardial infarction, RMI). However, the appropriate
      timing of reperfusion for RMI is unclear. METHODS: We retrospectively evaluated
      525 consecutive MI patients who underwent percutaneous coronary intervention
      (PCI) in our hospital between January 2008 and December 2012. RESULTS: Sixty RMI
      patients were more frequently associated with cardiac complications such as
      myocardial rupture (3.3% vs. 0%; p<0.01), ventricular septal rupture (3.3% vs.
      0.4%; p<0.05), and congestive heart failure (15% vs. 2.6%; p<0.001) than 272
      consecutive ST-elevation myocardial infarction (STEMI) patients. Of the 60 RMI
      patients, 33 (55.0%) underwent PCI within 7days (early-PCI group) and 27 (45.0%)
      underwent PCI after 7days (late-PCI group). Left ventricular ejection fraction
      measured by echocardiography at second hospital day was similar between the
      groups. The early-PCI group was more significantly associated with cardiogenic
      shock and heart failure and more frequently required intra-aortic balloon pumping
      (24.2% vs. 3.7%; p<0.05) than the late-PCI group. There were no significant
      differences in 30-day mortality, cardiac complications, and major cardiac events
      during long-term follow-up (12-36 months) between the groups. CONCLUSION: RMI
      patients had a higher incidence of cardiac complications than AMI patients.
      Clinical outcomes were similar between patients undergoing early
      revascularization and those undergoing late revascularization, although the
      former group included a higher proportion of patients with severe cardiac
      failure.

PMID- 29455787
TI  - Cardiovascular risk factors profile in patients with acute coronary syndrome with
      particular reference to left ventricular ejection fraction.
AB  - BACKGROUND: Acute coronary syndrome (ACS) remains a leading cause of death in the
      United States. Numerous studies have shown that the degree of LV systolic
      dysfunction is a major if not the most important determinant of long-term outcome
      in ACS. OBJECTIVES: To identify the most important risk factors and other
      clinical predictors which might have impact on left ventricular ejection fraction
      in patients with ACS. RESULTS: The total patients (299) admitted to our center
      from July, 2015 till December, 2015; with established diagnosis of ACS were
      classified in to two groups: Group I: 193 patients with impaired LVEF <40%
      (64.5%), Group II: 106 patients with LVEF equal or >40% (35.5%). The patients of
      group I were significant elderly compared to those of group II (60.9+/-11.2 vs
      56.9+/-10.6; p=0.002), had significant history of DM and CKD (66.3% and 31.1% VS
      49.1% and 19.8%; p=0.004 and 0.036 respectively), presented mainly with STEMI-
      ACS (51.3% VS 28.3% respectively; p<0.001) with +v cardiac biomarker (troponin)
      (90.2% VS 66.0%; p<0.001). Moreover, patients of group I had more significant
      ischemic MR compared to the patients of group II (24.9% VS 3.8% respectively;
      p<0.001) with higher rate of LV thrombus discovered by echocardiography (25.4% VS
      1.9%; p<0.001). Extensive significant CAD disease was observed to be higher among
      patients of group I (69.4% VS 57.5%; p=0.039) and those patients treated mainly
      with PCI revascularization therapy (68.9% VS 52.8%; p=0.002) compared to patients
      of group II who mainly treated medically (34.9% VS 17.6 %; p<0.001). Multiple
      logistic regression analysis demonstrated that DM (odd ratio (OR): 2.64, 95%
      confidence interval (CI): 1.45-4.79, P=0.01), presence of significant ischemic MR
      (OR: 13.7, 95% CI:2.84-66.1, p=0.001)and presence of significantly diseased
      coronary vessels (odd ratio (OR): 5.06, 95% confidence interval (CI): 1.14-22.6,
      P=0.033,) all were independent predictors for significant LV dysfunction (LVEF
      <40%) which predict poor outcome in ACS patients. CONCLUSION: We concluded that
      DM, presence of significant ischemic MR, and increased number, severity of
      diseased coronaries all were independent predictors of LV dysfunction (LVEF <40%)
      which is known to predict poor outcome. Identification of those risk predictors
      upon patient evaluation could be helpful to identify high risk-patients, in need
      of particular care, aggressive therapy and close follow-up to improve their poor
      outcome.

PMID- 29455788
TI  - Presence of coronary artery disease in diabetic and non diabetic South Asian
      immigrants.
AB  - INTRODUCTION: South Asian Immigrants (SAIs) are the second fastest growing Asian
      immigrant population in the US, and at a higher risk of type 2 diabetes
      (diabetes) and coronary artery disease (CAD) than the general US population.
      OBJECTIVES: We sought to determine in SAIs the; 1) the prevalence of CAD risk
      factors in diabetics and non-diabetics; and b) the high possibility of CAD in
      diabetic SAIs. We also assessed the prevalence of sub-clinical CAD in both
      diabetics and non-diabetics SAIs using common carotid artery Intima-media
      thickness (CIMT) as a surrogate marker for atherosclerosis. METHODS: In a cross
      sectional study design, 213 first generation SAIs were recruited and based on the
      history, and fasting glucose levels were divided into two subgroups; 35 diabetics
      and 178 non-diabetics. 12-hour fasting blood samples were collected for glucose
      and total cholesterol levels. Exercise Tolerance Test (ETT) was performed to
      determine the possibility of CAD. RESULTS: Both diabetics and non-diabetics SAIs
      in general, share a significant burden of CAD risk factors. The prevalence of
      hypertension (p=0.003), total cholesterol >=200mg/dl (p<0.0001) and family
      history of diabetes (p<0.0001) was significantly was significantly higher in
      diabetics compared to non-diabetics. Of the 22/29 diabetic participants without
      known history of CAD, 45% had positive ETT (p<0.001). Similarly, 63.1% of
      diabetics and 51.8 % of non-diabetics were positive for sub-clinical CAD using
      CIMT as a marker. CONCLUSION: The susceptibility to diabetes amongst SAIs
      promotes an adverse CAD risk, as evident by this small study. Further research,
      including larger longitudinal prospective studies, is required to validate the
      current small study findings with investigation of the temporal association.

PMID- 29455789
TI  - Geographical variation in the clinical presentation of endomyocardial fibrosis in
      India?
AB  - OBJECTIVES: To compare the clinical presentation, clinical profile and survival
      of two groups of endomyocardial fibrosis patients. METHODS: The study was a
      prospective cohort study, or a prospective case series, comparing all consecutive
      echocardiographically proven patients with endomyocardial fibrosis seen in
      Medical College Trivandrum with the patients seen in Medical College Hospital,
      Alappuzha(Alleppey) (or TD Medical College). In all patients the clinical details
      like age, sex, type of endomyocardial fibrosis, the presence of anaemia,
      eosinophilia, neutrophilia and type of rhythm(Sinus or atrial fibrillation) etc
      were compared by both simple X2 and by Kaplan Meier survival curves. RESULTS: The
      mean age and the sex distribution was same in both places Briefly the incidence
      of biventricular endomyocardial fibrosis was more from Trivandrum than Alleppey,
      64.9% vs 14.3% (p<0.0.001), the incidence of atrial fibrillation was more in
      Trivandrum 44.2% vs 16.3%. (p<0.001)The overall survival of Trivandrum patients
      was poorer (p<0.0001). The six year survival was 61% in the Trivandrum population
      whereas it was 91.5% in the Alleppey population. CONCLUSIONS: These differences
      may have been due to the better nutrition of the Alleppey patients due to a
      higher exposure to fish compared to the Trivandrum population. Better nutrition
      would protect against Magnesium deficiency and prevent the absorption of Cerium
      in the patients from Alleppey, compared to those from Trivandrum.

PMID- 29455790
TI  - Insertion/deletion polymorphism of ACE gene in females with peripartum
      cardiomyopathy: A case-control study.
AB  - BACKGROUND: The role of polymorphism of Angiotensin converting enzyme (ACE) gene
      and ACE activity in etiopathogenesis, prognosis, and many other clinical
      parameters in the various form of the cardiovascular disease has been established
      to some degree of certainty. The pathophysiology of Peripartum cardiomyopathy
      (PPCM) remains an area of active research. The main aim of our study was to see
      pattern of ACE- Insertion/Deletion (I/D) allele in PPCM and its implications on
      left ventricular performance indices. METHODS: This single-center case-control
      study included 45 cases and 70 controls. The diagnosis of PPCM was established
      clinically and echocardiographically. ACE genotyping was done by polymerase chain
      reaction (PCR) method in all subjects. RESULTS: The II, ID, and DD genotype was
      present in 16, 18 and 11 of subjects with PPCM and 48, 19 and 3 of controls
      respectively. The odds ratio for ACE-II genotype in cases vs. controls was 0.253
      (95% CI=0.114-0.558; p=0.007), for that of II genotype was 1.93 (95% CI=0.86-4.3;
      p=0.107) and for DD genotype was 7.225 (95% CI; 1.88-27.6; p=0.0039). Overall
      frequency of D allele in cases was significantly higher than controls (odds=4.25;
      95% CI=2.01-6.7; p=0.0001). Moreover, ejection fraction, left ventricular volume
      and linear dimensions were worse in patients with DD genotype. CONCLUSION: ACE DD
      genotype and overall frequency of D allele is significantly higher in patients
      with PPCM. Also, the presence of DD genotype is associated with worse systolic
      performance indices measured echocardiographically.

PMID- 29455791
TI  - Criss-cross heart: Transthoracic echocardiographic features.
AB  - OBJECTIVE: To study the echocardiographic features of criss-cross heart (CCH), a
      congenital cardiac anomaly characterized by crossed ventricular inflow streams,
      in Indian patients. METHODS: In this retrospective observational study, all
      pediatric echocardiograms performed in a single tertiary care institution in
      South India over a three-year period were scrutinized for a diagnosis of CCH.
      Demographic, clinical and echocardiographic data were collected from patients'
      medical records and echocardiographic database. Crossed ventricular inflow
      streams was identified when there was inability to visualize both atrio
      ventricular valves in a single imaging plane in cardiac four chamber view.
      RESULTS: CCH was diagnosed in five patients from 10,500 pediatric
      echocardiographic studies. The age at diagnosis ranged from one month to 8 years.
      Cyanosis was present in all but one of the five cases. Crossed ventricular inflow
      streams was present by definition in all cases, whereas superior-inferior
      ventricular relationship was present in only three cases. All cases were
      associated with ventricular septal defects. Atrio-ventricular discordance was
      seen in three cases and concordance in two. Ventriculo-arterial discordance was
      seen in three cases, concordance in one and double outlet right ventricle in one.
      Three cases had pulmonary stenosis and the other two had pulmonary arterial
      hypertension. Straddling of AV valve was observed in four cases and hypoplastic
      aortic arch in one case. CONCLUSION: CCH is an extremely rare congenital cardiac
      anomaly. Superior-inferior ventricular relationship often co-exists with CCH, but
      is not necessarily present in all cases. CCH requires early diagnosis because of
      its common association with diverse cardiac anomalies.

PMID- 29455792
TI  - Left ventricular structure and diastolic function by cardiac magnetic resonance
      imaging in hypertrophic cardiomyopathy.
AB  - OBJECTIVE: Diastolic dysfunction is common in hypertrophic cardiomyopathy (HCM)
      and hypertensive heart disease (HHD), but its relationships with left ventricular
      (LV) parameters have not been well studied. Our objective was to assess the
      relationship of various measures of diastolic function, and maximum left
      ventricular wall thickness (MLVWT) and left ventricular mass index (LVMI) in HCM,
      HHD and normal controls using cardiac magnetic resonance imaging (CMR). We also
      assessed LV parameters and diastolic function in relation to late gadolinium
      enhancement (LGE) and right ventricular (RV) hypertrophy in HCM. METHODS: 41
      patients with HCM, 21 patients with HHD and 20 controls were studied. Peak
      filling rate (PFR), time to peak filling (TPF), MLVWT and LVMI were measured
      using CMR. LGE and RV morphology were assessed in HCM patients. RESULTS: MLVWT
      correlated with TPF in HCM (r=0.38; p=0.02), HHD (r=0.58; p=0.01) and controls
      (r=0.54; p=0.01); correlation between MLVWT and TPF was weaker in HCM than HHD.
      LVMI did not correlate with diastolic function. In HCM, LGE extent correlated
      with MLVWT (tau=0.41; p=0.002) and with TPF (tau=0.29; p=0.02). The HCM patients
      with RV hypertrophy had higher MLVWT (p<0.001) and TPF (p=0.03) than patients
      without RV hypertrophy. CONCLUSION: MLVWT correlates with diastolic function
      (TPF) in HCM, HHD and controls. LVMI did not show significant correlation with
      TPF. The diastolic dysfunction in HCM is not entirely explained by wall
      thickening. LGE and RV involvement are associated with worse LV diastolic
      function, suggesting that these may be markers of more severe underlying
      myocardial disarray and fibrosis that contribute to diastolic dysfunction.

PMID- 29455793
TI  - Maternal and fetal outcome in operated vs non-operated cases of congenital heart
      disease cases in pregnancy.
AB  - OBJECTIVES: To study pregnancy outcomes in operated vs non-operated cases of
      congenital heart disease cases during pregnancy. MATERIALS AND METHODS: A total
      of 55 patients of congenital heart disease who delivered in the authors unit in
      last 10 years were taken in this retrospective study. These were divided into two
      groups Group 1:29 (52.7%) patient who had no cardiac surgery and Group 2:
      26(47.2%) who had cardiac surgery to correct their cardiac defect before
      pregnancy. All patients were evaluated for cardiac complications and outcome
      during pregnancy. Obstetric complications, mode of delivery and fetal outcome was
      compared in the two groups using statistical analysis. RESULT: The commonest
      lesion was atrial septal defect (ASD) seen in 22(40%) patients followed by
      ventricular septal defect (VSD) in 16(29%) .Congenital valvular disease 8(14.5%)
      and patent ductus arteriosus in 4(7.2%) cases. The mean age was 25.9 +/- 3.15
      years in Group 1 and 26.3 +/- 4.53 years in Group 2. The baseline characteristics
      were similar in the two groups. There was no difference in cardiac complications,
      NYHA deterioration and need of cardiac drugs in the two groups. Obstetric
      complications and mode of delivery were also similar in the two groups.Mean birth
      weight was 2516.65 +/- 514.04 gm in Group 1 and 2683.00 +/- 366.00 gm in Group 2
      and was similar. APGAR < 8, stillbirth rate and other neonatal complications were
      also similar in two groups. CONCLUSION: The maternal and fetal outcome was
      excellent in patients with congenital heart disease and was similar in unoperated
      and operated cases.

PMID- 29455794
TI  - Effect of ventricular function and volumes on exercise capacity in adults with
      repaired Tetralogy of Fallot.
AB  - OBJECTIVES: Investigate the effects of left and right ventricular function and
      severity of pulmonary valve regurgitation, quantified by cardiac magnetic
      resonance (CMR), on exercise tolerance in adult patients who underwent ToF repair
      at a young age. METHODS: This is a retrospective cohort study of 52 patients
      after ToF surgery and 33 age- and sex-matched healthy volunteers. CMR and
      cardiopulmonary exercise testing (CPET) were performed on all patients; CPET was
      performed on control subjects. RESULTS: The main finding of CPET was a severe
      decrease in oxygen uptake at peak exercise VO2peak in TOF patients. The patients
      were characterized also by lower pulse O2peak and heart rate at peak exercise.
      Ejection fraction of the right and left ventricles was correlated (r=0,32;
      p=0,03). Left ventricle ejection fraction was negatively correlated with right
      ventricular volumes (r=-0,34; p=0,01) and right ventricular mass (r=-046;
      p<0,00). Right ventricular mass was positively correlated with left ventricular
      variables (left ventricle end diastolic volume, r=0,43; p=0,002; left ventricle
      end systolic volume, r=0,54; p<0,00) as was VO2peak: LVEDV (r=0,38; p=0,01);
      LVESV (r=0,33; p=0,03) and LV mass (r=0,42; p=0,006). CONCLUSION: Exercise
      intolerance in adults with repaired ToF is markedly depressed. The decreased
      exercise capacity is correlated with impaired RV function and may be associated
      also with LV dysfunction, which suggests right-to-left ventricular interaction.

PMID- 29455795
TI  - Does resting heart rate measured by the physician reflect the patient's true
      resting heart rate? White-coat heart rate.
AB  - OBJECTIVES: In cardiology, resting heart rate (HR) and blood pressure (BP) are
      key elements and are used to adapt treatment. However HR measured in consultation
      may not reflect true resting HR. We hypothesize that there may be a "white-coat"
      effect like with BP and that there may be an association between HR variations
      and BP variations. METHODS: This prospective, monocentric, observational, pilot
      study (January-April 2016) included 57 consecutive ambulatory patients at
      Poitiers University Hospital, France (58% male, mean age 64 years). Patients'
      resting HR and BP were recorded with the same automated blood pressure
      sphygmomanometer in consultation by the physician then with self-measurement at
      home. RESULTS: In the overall cohort, we found that HR was significantly higher
      in consultation (70.5bpm+/-12.6 vs. 68.1bpm+/-10.1, p=0.034). HR also correlated
      with diastolic BP (r=0.45, p=0.001). Patients were divided into three groups to
      look for associations with BP: masked HR, (higher HR at home, 38.6%), white-coat
      HR, (lower HR at home 52.6%) and iso HR, (no change between HR at home and
      consultation, 8.8%). Although there was no difference between groups in diastolic
      BP measured in consultation, home diastolic BP was lower in the white-coat HR
      group (74.3mmHg+/-9.8 vs. 77.9mmHg+/-7.5, p=0.016). CONCLUSIONS: Our study brings
      to light an exciting idea that could have a major therapeutic and maybe
      prognostic impact in cardiology: resting HR measured by the physician in
      consultation does not reflect true resting HR. This must be taken into account to
      adapt treatment.

PMID- 29455797
TI  - From the Editor's desk...: March 2018.

PMID- 29455796
TI  - Percutaneous transradial artery approach for femoro- popliteal artery
      intervention in the current era in Japan.
AB  - The percutaneous transradial artery approach for coronary angiography and
      intervention has been recognized as a safe and effective method, however, it is
      limited for endovascular therapy (EVT) for femoro-popliteal artery because of
      lack of devices with longer shaft. Herein, we report two EVT cases for
      superficial femoral artery disease treated with a long shaft balloon through the
      radial artery. Although femoro-popliteal artery intervention with this approach
      has several limits for available devices and technical issues, it is effective
      for particular patients who are impossible in EVT with femoral artery approach.

PMID- 29455798
TI  - Immunopathogenesis of Primary Graft Dysfunction After Lung Transplantation.

PMID- 29455799
TI  - Tricuspid Valve Repair: How I Teach It.

PMID- 29455800
TI  - Invited Commentary.

PMID- 29455801
TI  - Invited Commentary.

PMID- 29455802
TI  - Invited Commentary.

PMID- 29455803
TI  - Invited Commentary.

PMID- 29455804
TI  - Step-by-Step Aortic Valve Replacement With a New Rapid Deployment Valve.
AB  - PURPOSE: Rapid deployment/sutureless aortic valve replacement is aimed at
      minimizing the invasiveness of surgical aortic valve replacement. We describe the
      implantation techniques of a new rapid deployment aortic valve, focusing on its
      unique and challenging features. DESCRIPTION: The EDWARDS INTUITY Elite aortic
      valve (Edwards Lifesciences, Irvine, CA) represents a hybrid between the surgical
      PERIMOUNT Magna Ease (Edwards Lifesciences) pericardial valve, but with advanced
      features of the percutaneous SAPIEN valve system (Edwards Lifesciences). A
      flexible delivery system, with a balloon-expandable subannular frame, facilitates
      insertion. Important implantation steps include an extended oblique "hockey
      stick" aortotomy, symmetrical annular debridement, intra-annular and supra
      annular sizing, guiding suture placement, and balloon expansion of the subannular
      valve frame. EVALUATION: Although this valve provides advantages over
      conventional aortic valves, its implantation is unique, and special operative
      considerations must be heeded for optimal outcomes. Implantation requires minimal
      suturing, enabling smaller incisions. Also, the intra-annular inflow frame may
      promote improved hemodynamics. CONCLUSIONS: The INTUITY Elite system represents a
      significant innovation in bioprosthesis technology. It has been shown to be safe
      and effective, but its implantation requires detailed attention to several unique
      operative steps.

PMID- 29455805
TI  - The Coroneo External Annuloplasty Ring.

PMID- 29455806
TI  - Reply.

PMID- 29455807
TI  - Reply.

PMID- 29455808
TI  - Aortic Leaflet Stress in Surgery for Genetically Determined Root Aneurysms:
      Biomechanical Insights.

PMID- 29455810
TI  - Reply.

PMID- 29455809
TI  - More Aggressive Intervention Contributes to Avoiding Recurrent Tricuspid
      Regurgitation.

PMID- 29455811
TI  - Sutureless Valve Thrombosis: The Role of Stent Geometry.

PMID- 29455812
TI  - Reply.

PMID- 29455813
TI  - The Discrepancy Between Two Clinical Trials: Dose-Dependent or Tumor
      Characteristics?

PMID- 29455814
TI  - TNM Staging System and Surgical Resection for Partially Solid Lung
      Adenocarcinoma.

PMID- 29455815
TI  - Reply.

PMID- 29455816
TI  - There Are Many Unnecessary Patch Plasty Operations in Tetralogy of Fallot.

PMID- 29455817
TI  - Skin Perforator Flap Pedicled With Intercostal Muscle: Additional Data.

PMID- 29455818
TI  - Mitral Regurgitation Exacerbation Due to Sutureless Aortic Valve Replacement.
AB  - Sutureless aortic valves are increasingly used for aortic valve replacement (AVR)
      with excellent outcomes. Implantation requires device expansion in a subannular
      position within the native aortic root. We report a patient with severe aortic
      stenosis who received a Perceval sutureless AVR (LivaNova, London, United
      Kingdom), resulting in a competent prosthesis with an absence of paravalvular
      leak and aortic regurgitation. However, this implantation resulted in the
      exacerbation of mitral regurgitation. The sutureless valve required explantation,
      and a traditional sutured valve was subsequently implanted, which returned the
      mitral regurgitation to baseline. We discuss a potential etiology of this
      sutureless AVR-specific complication.

PMID- 29455819
TI  - Resection of Metastatic Hepatocellular Carcinoma in the Ventricular Septum
      Causing Left Ventricular Outflow Tract Obstruction.
AB  - Isolated cardiac involvement of recurrent metastatic hepatocellular carcinoma
      (HCC) is extremely rare. We report a patient with left ventricular outflow tract
      (LVOT) obstruction due to isolated recurrent HCC involving the interventricular
      septum (IVS). A ventriculotomy with resection of the tumor and patch repair of
      the IVS was performed with successful relief of LVOT obstruction. The patient was
      discharged home 6 days later symptom-free.

PMID- 29455820
TI  - Ductus Aneurysm Ruptured Into the Esophagus With Massive Bleeding.
AB  - We report a patient with life-threatening hematemesis caused by the rupture of a
      ductus aneurysm into the esophagus, which was successfully treated by coil
      embolism for the esophageal fistula through the aorta and subsequent thoracic
      endovascular aortic replacement. Second-stage therapy was performed surgically
      after proactive antibiotic treatment and in consideration of the patient's
      improved general condition. This included debridement with drainage, aortic
      encasement with remnant aneurysmal wall, omentopexy, and jejunostomy. The
      esophagus was preserved, and satisfactory healing and natural closure of the
      fistula were achieved. Although repeated aspirations were later required for
      pleural fluid, such inflammatory complications finally subsided.

PMID- 29455821
TI  - Pulmonary Hemorrhage After Arterial Switch Operation.
AB  - Major aortopulmonary collateral arteries can influence the postoperative course
      of arterial switch operation, with heart failure being the common clinical
      presentation. A relatively rare presentation of an aortopulmonary collateral
      artery in the form of persistent postoperative pulmonary hemorrhage was
      encountered after an uneventful arterial switch operation in a neonate with
      transposition of the great arteries, intact interventricular septum, and situs
      inversus totalis. The aortopulmonary collateral artery was coil embolized with a
      successful outcome.

PMID- 29455822
TI  - Pulmonary Hemorrhage Due to Unrecognized Bronchial Collateral After Arterial
      Switch Operation.
AB  - We report a neonate with transposition of great arteries and intact ventricular
      septum who had a massive pulmonary hemorrhage soon after an arterial switch
      operation. An emergency cardiac catheterization revealed a large bronchial
      collateral artery from the descending aorta feeding the right lung. The
      hemorrhage was controlled by coil embolization of the collateral, and the patient
      recovered after prolonged intensive care.

PMID- 29455823
TI  - Sequential Melody Valve Insertion After Repair of Tetralogy of Fallot
      Atrioventricular Septal Defect.
AB  - Repair of tetralogy of Fallot with atrioventricular septal defect may be
      associated with hemodynamic challenges in the postoperative period particularly
      as left atrial hypertension secondary to left atrioventricular valve dysfunction
      may exacerbate pulmonary regurgitation and augment low cardiac output. We present
      a case describing hybrid strategies to treat severe left atrioventricular and
      pulmonary valve regurgitation with modified balloon expandable stent valves to
      counter low cardiac output secondary to valve dysfunction. Such strategies offer
      an alternative to standard valve choices and should be considered as an extension
      of the current surgical valve inventory.

PMID- 29455824
TI  - Anomalous Left Coronary Artery From Pulmonary Artery in a Baby With Pulmonary
      Atresia, Intact Ventricular Septum.
AB  - A baby with pulmonary atresia with intact ventricular septum and hypoplastic
      right ventricle, with suspected right ventricle to coronary communications, was
      operated on for placing an aortopulmonary shunt. Postoperatively, the baby
      deteriorated with features of myocardial ischemia. Postmortem examination
      revealed anomalous origin of left coronary artery from pulmonary artery that
      caused significant coronary ischemia on ligation of the ductus arteriosus.
      Although coronary anomalies, including right ventricle dependent coronary
      circulation, has been well described, this is the first report of anomalous
      origin of coronary artery from pulmonary artery in a baby with pulmonary atresia
      and intact ventricular septum.

PMID- 29455825
TI  - Urgent Surgical Approach to Mediastinal Cyst Causing Life-Threatening Tracheal
      Obstruction.
AB  - This case describes an urgent surgical approach to a patient with symptoms of
      rapid progressive respiratory compromise resulting from a massive mediastinal
      cyst. To relieve tracheal compression, ultrasound-guided percutaneous fine-needle
      aspiration was performed as an urgent procedure, which immediately improved the
      patient's airway obstruction and facilitated double-lumen endotracheal
      intubation. Methylene blue was injected into the cyst through the puncturing
      needle and accurately marked the margins of the cyst. The cyst was completely
      resected under thoracoscopy. The signs and symptoms of airway obstruction
      resolved after the operation, with no recurrence observed during the 1-year
      follow-up.

PMID- 29455826
TI  - Spontaneous Regression of Primary Pulmonary Synovial Sarcoma.
AB  - We report a rare case of primary pulmonary synovial sarcoma that underwent
      spontaneous regression after a transbronchial biopsy. A 38-year-old woman with a
      well-demarcated solitary mass shadow on chest roentgenogram was referred to us. A
      transbronchial biopsy was performed, and immunohistochemical results as well as
      detection of SYT-SSX1 (SYnovial sarcoma Translocation-Synovial Sarcoma X
      chromosome breakpoint) transcripts resulted in a diagnosis of synovial sarcoma. A
      right lower lobectomy was performed during video-assisted thoracoscopic surgery.
      Pathologic examination revealed widespread coagulative necrosis with feeding
      arterioles occluded by organized thrombi. To our knowledge, this is the first
      report of a case of spontaneous regression of primary pulmonary synovial sarcoma.

PMID- 29455827
TI  - Paraneoplastic Neuromyelitis Optica Spectrum Disorder as Presentation of
      Esophageal Adenocarcinoma.
AB  - Neuromyelitis optica spectrum disorders are a group of relapsing, inflammatory,
      demyelinating neurologic syndromes involving the central nervous system
      associated with antibodies against aquaporin-4. Although most commonly an
      idiopathic autoimmune condition, neuromyelitis optica may occur as a
      paraneoplastic syndrome in rare instances. We report a case of transverse
      myelitis caused by paraneoplastic neuromyelitis optica as the presenting clinical
      syndrome in a patient with esophageal adenocarcinoma.

PMID- 29455828
TI  - Late Disruption of Valved Graft at Nonanastomotic Site After Bentall Operation.

PMID- 29455829
TI  - Caught in the Act: Massive Pulmonary Thrombus Crossing a Patent Foramen Ovale.

PMID- 29455830
TI  - Transaortic Alfieri Edge-to-Edge Repair for Functional Mitral Regurgitation.
AB  - There is controversy about handling functional mitral regurgitation in patients
      undergoing aortic valve or proximal aortic operations. We describe a transaortic
      Alfieri edge-to-edge repair for functional mitral regurgitation that reduces
      operative excessive invasion and prolonged cardiopulmonary bypass time. Between
      May 2013 and December 2016, 10 patients underwent transaortic Alfieri edge-to
      edge mitral repair. There were no operative deaths. The severity of mitral
      regurgitation immediately after the operation by transesophageal echocardiography
      was none or trivial in all patients. A transaortic Alfieri edge-to-edge repair
      for functional mitral regurgitation is a simple and safe approach.

PMID- 29455831
TI  - Thoracoscopic Sympathectomy for Refractory Electrical Storm After Coronary Artery
      Bypass Grafting.
AB  - We report a patient with refractory electrical storm after coronary artery bypass
      grafting who was successfully treated with thoracoscopic sympathectomy. Cardiac
      arrest with ventricular tachycardia occurred on postoperative day 2, and the
      patient required emergency support with venoarterial extracorporeal membrane
      oxygenation. Frequent episodes of ventricular tachycardia prevented cardiac
      recovery and weaning from mechanical circulatory support. A percutaneous left
      stellate ganglion block initially demonstrated successful prevention of
      ventricular tachycardia, and definitive sympathetic denervation was achieved by a
      left thoracoscopic sympathectomy. The patient remained in normal sinus rhythm and
      gained recovery of baseline ventricular function, permitting successful
      decannulation and weaning of inotropic support.

PMID- 29455832
TI  - Diagnostic and Therapeutic Implications of Ultrasound Imaging of Perianal
      Fistulous Tracts in Patients with Suspected Hidradenitis Suppurativa.

PMID- 29455833
TI  - Acquired Dermal Melanocytosis on the Back of a Patient With Psoriasis.

PMID- 29455834
TI  - Alkaloid Synthesis Using Organocatalysts.
AB  - This chapter covers the literature since the advent, in the 21st century, of
      total syntheses of alkaloids using enantio- or diastereoselective organocatalytic
      reactions to construct the alkaloid scaffolds. The details of these alkaloid
      syntheses are described separately for each basic skeleton, including indole,
      indoline, oxindole, and piperidine alkaloids.

PMID- 29455835
TI  - Moschamine-Related Indole Alkaloids.
AB  - Moschamine-related alkaloids originate mainly from feruloylserotonin by
      cyclization or dimerization. This review provides a comprehensive overview on the
      achievements in the field of moschamine-related alkaloids. In the isolation part,
      a detailed structural characterization of moschamine-related alkaloids is
      followed by their spectral data. Besides the well-known antioxidative activities,
      other screened biological properties are also outlined. Since their isolation,
      different protocols have been developed to synthesize these alkaloids. The
      synthetic part is organized according to the different synthetic methodologies
      for the formation of key structural elements.

PMID- 29455836
TI  - The Rigidins: Isolation, Bioactivity, and Total Synthesis-Novel Pyrrolo[2,3
      d]Pyrimidine Analogues Using Multicomponent Reactions.
AB  - Rigidins (2-6) are pyrrolopyrimidine alkaloids isolated from marine tunicates.
      Since their isolation, refinement of their total syntheses, and biochemical
      evaluation, interest toward this pyrrolo[2,3-d]pyrimidine scaffold as a medicinal
      candidate has been triggered. The derivatization of these natural products has
      led to the discovery of a novel range of 7-deazahypoxanthines, which exhibit
      extremely potent anticancer activity in human cancer cell lines. A major
      breakthrough toward the synthesis of rigidin and various rigidin analogues has
      been the application of multicomponent reactions (MCRs). The rapid assembly of
      molecular diversity and flexibility displayed by MCRs makes it an attractive
      strategy for the preparation of rigidin-inspired small molecules. Furthermore, a
      number of rigidin-like 7-deazaxanthine compounds have been reported in the
      literature and the popularity of implementing MCRs to construct these 7
      deazaxanthines is highlighted here. It is our hope that the synthetic methods
      described in this chapter will result in the further generation of rigidin
      inspired compounds that will move on from being "hits" into "leads" in the
      medicinal chemistry drug discovery pipeline and potentially into anticancer
      therapeutics.

PMID- 29455837
TI  - Benzoxazole Alkaloids: Occurrence, Chemistry, and Biology.
AB  - Benzoxazole alkaloids exhibit a diverse array of structures and interesting
      biological activities. In spite of the extensive research done on the synthesis
      and biology, till date there is no concise update on this class of alkaloids.
      This chapter summarizes the literature on benzoxazole alkaloids till March 2017,
      which covers their isolation, characterization, possible biosynthetic origins,
      biological activities, and major synthetic approaches. These alkaloids have been
      broadly classified in the context of their sources, namely (i) fungal origin,
      (ii) marine origin, and (iii) plant origin.

PMID- 29455838
TI  - Preface.

PMID- 29455839
TI  - Discussion of "Effects of radiation and surgery on function and quality of life
      in rectal cancer patients".

PMID- 29455840
TI  - Cardiac Surgery Outcomes in Patients With Chronic Lymphocytic Leukemia.
AB  - BACKGROUND: Surgical outcomes of patients with chronic lymphocytic leukemia (CLL)
      undergoing cardiac surgery are limited. Our objectives were to investigate
      hospital morbidity and mortality after open cardiac surgery in CLL versus non-CLL
      patients. METHODS: From May 1995 to May 2015, 157 patients with CLL and 55,917
      without and older than 47 years underwent elective cardiac surgery at Cleveland
      Clinic. By Rai criteria, 79 CLL patients (56%) were low risk (class 0), 13 (9.1%)
      intermediate risk (classes I and II), and 38 (27%) high risk (classes III and
      IV); 12 (8.5%) were in remission. Mean age of CLL patients was 72 +/- 9.0 years,
      and 18% were women. CLL patients were propensity-score matched to 3 non-CLL
      patients to compare surgical outcomes. RESULTS: High-risk CLL patients received
      more blood products than matched non-CLL patients (33/38 [87%] versus 74/114
      [65%], p = 0.01), but were less likely to receive cryoprecipitate (0% versus
      15/114 [13%], p = .02). Intermediate-risk CLL patients received more platelet
      units, mean 12 versus 4.6 (p = 0.008). Occurrence of deep sternal wound infection
      (0% versus 5/471 [1.1%]), septicemia (5/157 [3.2%] versus 14/471 [3.0%]), and
      hospital mortality (4/157 [2.5%] versus 14/471 [3.0%]) were similar (p > 0.3),
      independent of prior chemotherapy treatment for CLL. CONCLUSIONS: Although CLL
      patients did not have higher hospital mortality than non-CLL patients, high-risk
      CLL patients were more likely to receive blood products. Risks associated with
      transfusion should be considered when evaluating CLL patients for elective
      cardiac surgery. Appropriate preoperative management, such as blood product
      transfusions, and alternative treatment options that decrease blood loss, should
      be considered for high-risk patients.

PMID- 29455841
TI  - Actual 10-year survival after hepatic resection of colorectal liver metastases:
      what factors preclude cure?
AB  - BACKGROUND: Hepatic resection of colorectal liver metastases is associated with
      long-term survival. This study analyzes actual 10-year survivors after resection
      of colorectal liver metastases, reports the observed rate of cure, and identifies
      factors that preclude cure. METHODS: A single-institution, prospectively
      maintained database was queried for all initial resections for colorectal liver
      metastases for the years 1992-2004. Observed cure was defined as actual 10-year
      survival with either no recurrence or resected recurrence with at least 3 years
      of disease-free follow-up. Clinical risk score was dichotomized into low (0-2)
      and high (3-5). Semiparametric proportional hazards mixture cure model was
      utilized to estimate probability of cure. RESULTS: We included 1,211 patients
      with a median follow-up for survivors of 11 years. Median disease-specific
      survival was 4.9 years (95% CI: 4.4-5.3). 295 patients (24.4%) were actual 10
      year survivors. The observed cure rate was 20.6% (n = 250). Among 250 cured
      patients, 192 (76.8%) had no recurrence and 58 (23.2%) had a resected recurrence
      with at least 3 years of disease-free follow-up. Extrahepatic disease (n = 88),
      carcinoembryonic antigen >200 ng/mL (n = 119), positive margin (n = 109), and >10
      tumors (n = 31) had observed cure rates less than 10%. In cure model analysis,
      patients with both extrahepatic disease and high clinical risk score (n = 31) had
      an estimated probability of cure of 3.5%. CONCLUSION: Actual 10-year survival
      after resection of colorectal liver metastases is 24% with an observed 20% cure
      rate. Patients with both high clinical risk score and extrahepatic disease have
      an estimated probability of cure less than 5%. When such factors are identified,
      strong consideration may be given to preoperative strategies, such as neoadjuvant
      chemotherapy, to help select patients for surgical therapy.

PMID- 29455842
TI  - Databases for surgical health services research: National cancer database.

PMID- 29455843
TI  - The potential for spills and leaks of contaminated liquids from shale gas
      developments.
AB  - Rapid growth of hydraulic fracturing for shale gas within the USA and the
      possibility of shale developments within Europe has created public concern about
      the risks of spills and leaks associated with the industry. Reports from the
      Texas Railroad Commission (1999 to 2015) and the Colorado Oil and Gas Commission
      (2009 to 2015) were used to examine spill rates from oil and gas well pads.
      Pollution incident records for England and road transport incident data for the
      UK were examined as an analogue for potential offsite spills associated with
      transport for a developing shale industry. The Texas and Colorado spill data
      shows that the spill rate on the well pads has increased over the recorded time
      period. The most common spill cause was equipment failure. Within Colorado 33% of
      the spills recorded were found during well pad remediation and random site
      inspections. Based on data from the Texas Railroad Commission, a UK shale
      industry developing well pads with 10 lateral wells would likely experience a
      spill for every 16 well pads developed. The same well pad development scenario is
      estimated to require at least 2856 tanker movements over two years per well pad.
      Considering this tanker movement estimate with incident and spill frequency data
      from UK milk tankers, a UK shale industry would likely experience an incident on
      the road for every 12 well pads developed and a road spill for every 19 well pads
      developed. Consequently, should a UK shale industry be developed it is important
      that appropriate mitigation strategies are in place to minimise the risk of
      spills associated with well pad activities and fluid transportation movements.

PMID- 29455844
TI  - [Occipital sinus pericranii: About an unusual situation and review of the
      literature].
AB  - The sinus pericranii refers to a set of clinical presentations that share a
      pathological communication between the scalp veins and the underlying cranial
      venous sinus. The nature of this connection ranges from the simple dilatation of
      the emissary veins, to wide connections through a calvarial bone loss leaving
      almost the cranial venous sinus in direct contact with the subcutaneous tissue.
      The authors present the case of an occipital pericranii sinus of intraoperative
      discovery. Congenital, post-traumatic or spontaneous, this anomaly is most often
      frontal and located on or close to the midline. The usual clinical presentation
      is that of a soft mass that empties to the pressure while standing, while it
      fills in all situations that increase the intracranial pressure (Valsalva
      maneuver ...). The diagnosis is not always easy to establish, and relies on a
      bundle of clinical and radiological arguments. Through a review of the literature
      we propose to focus on the clinical features, diagnostic means and therapeutic
      options of this rare entity.

PMID- 29455845
TI  - Single-Cell Resolution of T Cell Immune Responses.
AB  - Single antigen-specific B or T lymphocytes are the smallest functional units,
      into which an adaptive immune response can be dissected. Today, novel high
      throughput technologies are providing researches with increasingly complex
      information on the diverse phenotypic signatures of individual lymphocytes. With
      a focus on T cells, we summarize here, how computational approaches are becoming
      increasingly important to identify the relevant developmental boundaries and
      connections between these high-dimensional lymphocyte states. We then describe
      how these insights may be further expanded by novel experimental approaches that
      allow to map the fate of individual T cells and their progeny in vivo and in
      vitro. Finally, we highlight how these experiments have uncovered a probabilistic
      regulatory structure of T cell immune responses and briefly discuss, how two
      distinct theoretical frameworks used to describe this structure may be merged to
      best capture single T cell behavior in computational terms.

PMID- 29455848
TI  - Caveolin-1: The Unnoticed Player in TCR and BCR Signaling.
AB  - T and B lymphocytes are key players of the adaptive immune system. They recognize
      pathogenic cues via the T cell antigen receptor (TCR) and the B cell antigen
      receptor (BCR) to get activated and execute their protective function. TCR and
      BCR signaling are initiated at the plasma membrane and subsequently propagated
      into the cell, ultimately leading to cell activation and a protective immune
      response. However, inappropriate activation of T and B cells can be detrimental
      to the host resulting in autoimmune disorders, immunodeficiencies, and cancer.
      The TCR and BCR are located at the plasma membrane, which composition is highly
      heterogenic. Membrane compartmentalization based on specific lipid-lipid and
      protein-lipid interactions has raised the interest of the scientific community,
      converting the plasma membrane into an active player in the initiation of
      signaling and adding an additional layer of regulation to our current
      understanding of the functioning of antigen receptors. Caveolin-1 is an integral
      membrane protein and a crucial component of caveolae. It has been long thought
      that lymphocytes lack Caveolin-1 expression, due to the absence of detectable
      caveolae in lymphocytes and the failure to detect Caveolin-1 in T and B cell
      lines. However, Caveolin-1 is expressed at low levels in primary lymphocytes, and
      recent studies have shown the importance of Caveolin-1 for the basal membrane
      organization of the BCR and the TCR as well as their reorganization upon
      activation. Here, we review our current understanding of the initial signaling
      events of TCR and BCR activation with respect to receptor compartmentalization on
      the plasma membrane and with special emphasis on the previously unnoticed role of
      Caveolin-1.

PMID- 29455847
TI  - The Fate Choice Between Effector and Memory T Cell Lineages: Asymmetry, Signal
      Integration, and Feedback to Create Bistability.
AB  - CD8+ T cells clear primary infections with intracellular pathogens and provide
      long-term immunity against reinfection. Two different types of CD8+ T cells are
      responsible for these functions: short-lived effector T cells and memory T cells.
      The cellular relationship between these two types of CD8+ T cells has been
      subject to much investigation. Both cell types can derive from a single naive
      CD8+ T cell precursor. Their generation requires a fate choice early during a T
      cell response. As a result, two populations of T cells emerge. One of these
      consists of terminally differentiated short-lived effector T cells. The other
      contains cells able to develop into long-lived memory T cells. A foundation for
      development of these two populations may be laid during the first division of an
      activated naive T cell precursor, as a consequence of asymmetric segregation of
      fate-determining factors into the daughter cells. Nonetheless, the binary choice
      between the two lineages is strongly influenced by signals, which ensure that the
      differentiation process is matched with the needs posed by the infection. Here,
      we will discuss the genetic and metabolic programs governing differentiation of
      these two lineages as well as the processes leading to their induction and
      consolidation to create bistability. These processes involve extensive lateral
      inhibition between the programs as well as positive feedback between the genetic
      programs and the signaling pathways responsible for their induction. These
      features will be highlighted by discussing the role of the Notch signaling
      pathway in guiding the decision between the two lineages.

PMID- 29455846
TI  - The Unusual Genetics and Biochemistry of Bovine Immunoglobulins.
AB  - Antibodies are the key circulating molecules that have evolved to fight infection
      by the adaptive immune system of vertebrates. Typical antibodies of most species
      contain six complementarity-determining regions (CDRs), where the third CDR of
      the heavy chain (CDR H3) has the greatest diversity and often makes the most
      significant contact with antigen. Generally, the process of V(D)J recombination
      produces a vast repertoire of antibodies; multiple V, D, and J gene segments
      recombine with additional junctional diversity at the V-D and D-J joints, and
      additional combinatorial possibilities occur through heavy- and light-chain
      pairing. Despite these processes, the overall structure of the resulting antibody
      is largely conserved, and binding to antigen occurs predominantly through the CDR
      loops of the immunoglobulin V domains. Bovines have deviated from this general
      paradigm by having few VH regions and thus little germline combinatorial
      diversity, but their antibodies contain long CDR H3 regions, with substantial
      diversity generated through somatic hypermutation. A subset of the repertoire
      comprises antibodies with ultralong CDR H3s, which can reach over 70 amino acids
      in length. Structurally, these unusual antibodies form a beta-ribbon "stalk" and
      disulfide-bonded "knob" that protrude far from the antibody surface. These long
      CDR H3s allow cows to mount a particularly robust immune response when immunized
      with viral antigens, particularly to broadly neutralizing epitopes on a
      stabilized HIV gp140 trimer, which has been a challenge for other species. The
      unusual genetics and structural biology of cows provide for a unique paradigm for
      creation of immune diversity and could enable generation of antibodies against
      especially challenging targets and epitopes.

PMID- 29455849
TI  - Relationship Between Proximal Aorta Morphology and Progression Rate of Aortic
      Stenosis.
AB  - BACKGROUND: The aim of this study was to examine the association between abnormal
      morphology of the proximal aorta and aortic stenosis (AS) progression rate. The
      main hypothesis was that morphologic changes of the proximal aorta, such as
      effacement of the sinotubular junction (STJ), result in increased biomechanical
      stresses and contribute to calcification and progression of AS. METHODS: Between
      2010 and 2012, 426 patients with mild to moderate AS were included in this study.
      Proximal aortic dimensions were measured at three different levels (i.e., sinus
      of Valsalva, STJ, and ascending aorta), and sinuses of Valsalva/STJ and ascending
      aorta/STJ ratios were used to determine degree of aortic deformity. AS
      progression rate was assessed by annualized increase in mean gradient (median
      follow-up time, 3.1 years; interquartile range, 2.6-3.9 years). The degree of
      aortic flow turbulence was examined in 18 matched patients with and without STJ
      effacement using cardiac magnetic resonance phase-contrast imaging. RESULTS:
      Patients' mean age was 71 +/- 13 years, and 64% were men. Patients with low
      ratios had greater AS progression (P < .05). After comprehensive adjustment,
      sinuses of Valsalva/STJ (P = .025) and ascending aorta/STJ (P = .027) ratios were
      independently associated with greater AS progression rate. Compared with patients
      without STJ effacement, those with effacement of the STJ had higher degrees of
      aortic flow turbulence (24.4% vs 17.2%, P = .038). CONCLUSIONS: Effacement of the
      STJ is independently associated with greater AS progression, regardless of
      arterial hemodynamics, aortic valve phenotype, or baseline AS severity. Patients
      with abnormal proximal aortic geometry had disturbed aortic flow patterns. These
      findings suggest an interrelation between proximal aorta morphology and stenosis
      progression.

PMID- 29455851
TI  - Opioids: A Pediatric Epidemic.

PMID- 29455850
TI  - Proteins involved in the antioxidant and inflammatory response in rutin-treated
      human skin fibroblasts exposed to UVA or UVB irradiation.
AB  - BACKGROUND: Rutin, due to its polyphenolic structure, has antioxidant properties
      and can be used as a cytoprotective compound against UV-induced effects on skin
      cells. OBJECTIVE: The aim of this study was to examine the effect of rutin on
      proteomic profile in human skin fibroblasts irradiated with UV dose that induces
      apoptosis. METHODS: Proteome analysis based on the results obtained by the
      QExactive OrbiTrap mass spectrometer. RESULTS: Results show that rutin treatment
      more strongly protects against UVA-induced rather than UVB-induced increases in
      the total expression of proteins involved in antioxidant (such as SOD, TrxR, and
      Prxs 1/2) and inflammatory response (e.g., IL-17F, PAK2, and YWHAZ). However, in
      the case of UVB-irradiated cells, rutin additionally enhances the levels of
      disulfide-isomerase - an enzyme that is responsible for the formation and
      breakage of disulfide bonds. Moreover, UVB radiation promotes rutin-Keap1 adduct
      formation, which leads to the activation of Nrf2, a factor that is responsible
      for the synthesis of cytoprotective proteins. Furthermore, rutin partially
      prevents UV-induced apoptosis by restoring the physiological levels of p53,
      cytochrome c, and cell cycle and apoptosis regulator protein 2 that were
      increased following irradiation. CONCLUSION: In conclusion, our results show that
      rutin effectively prevents UV-induced damages associated with proinflammatory and
      prooxidative activity and protects cells against apoptosis.

PMID- 29455853
TI  - Erratum.

PMID- 29455852
TI  - Disaster Preparedness: Meeting the Needs of Children.

PMID- 29455854
TI  - Pathophysiology and Management of Mild to Moderate Pediatric Atopic Dermatitis.
AB  - Atopic dermatitis (AD), or eczema, is a chronic inflammatory skin condition
      characterized by relapsing pruritic and dry, scaly lesions. AD affects 10% to 20%
      of children in the United States and significantly affects the quality of life of
      patients and their families. Primary care providers (PCPs) are often the first
      point of contact for the management of AD symptoms. As many as 70% of patients
      with mild to moderate disease can be managed by a PCP, underscoring the need for
      these providers to understand basic AD pathophysiology and current standards of
      care. This article will discuss the basic principles of AD diagnosis and
      management that PCPs need to optimize patient care, including AD pathogenesis,
      appropriate use of currently available topical therapies, basic skin care
      practices, and patient/caregiver counseling points. This article is sponsored by
      Spire Learning and supported by an educational grant from Pfizer Inc.

PMID- 29455855
TI  - Impact of Degree of Obesity on Sleep, Quality of Life, and Depression in Youth.
AB  - OBJECTIVE: Obese youth are more likely to report difficulties with sleep,
      depression, and quality of life (QOL). This study aims to characterize sleep
      problems, QOL, and symptoms of depression by degree of obesity. METHOD: The cross
      sectional study was conducted in a specialized obesity clinic. Obese youth and
      their caregivers (N = 150) were evaluated with the Child Sleep Habits
      Questionnaire and Pediatric Quality of Life. Youth completed the Children's
      Depression Inventory. Regression models and correlations were calculated.
      RESULTS: Degree of obesity was predictive of increased sleep difficulties and
      decreased QOL scores. Children's Depression Inventory scores showed that children
      with more symptoms of depression had more sleep problems, and these were not
      associated with the degree of obesity. Adolescents with more difficulties
      sleeping also reported more symptoms of depression and lower QOL. CONCLUSIONS:
      Degree of obesity negatively affected QOL and sleep variables. Patients with
      greater sleeping difficulties reported more symptoms of depression.

PMID- 29455856
TI  - Towards the development of a modeling framework to track nitrogen export from
      lowland artificial watersheds (polders).
AB  - Excess nitrogen (N) export from lowland artificial watersheds (polders) is often
      assumed to be a major contributor to the cultural eutrophication of downstream
      aquatic ecosystems. However, the complex transport processes characterizing
      lowland areas pose significant challenges in accurately quantifying their actual
      role. In this study, we developed a dynamic model to track N sources and
      transport pathways in lowland polders. The model is able to accommodate all the
      unique characteristics of polder dynamics, including artificial drainage, and
      interactions among surface water, groundwater and soil water. Our model was
      calibrated and validated against water level data and nitrogen concentrations
      measured in a lowland polder (Polder Jian) in China during the 2014-2016 period.
      Model performance was satisfactory with an R2 value of 0.55 and an NS value of
      0.53 for total N concentrations. The characterization of the various components
      of water budget and N cycle derived by the model was on par with local empirical
      estimates. N export from Polder Jian was approximately 57 kg ha-1 yr-1 and was
      distinctly higher than values reported from nearby non-polder areas. The largest
      fraction of N export stemmed from seepage. To our knowledge, this is the first
      dynamic model to quantify N export from a watershed with artificial drainage
      network and can be used to design remedial measures of ecosystem degradation.

PMID- 29455857
TI  - Comprehensive Analysis of Constraint on the Spatial Distribution of Missense
      Variants in Human Protein Structures.
AB  - The spatial distribution of genetic variation within proteins is shaped by
      evolutionary constraint and provides insight into the functional importance of
      protein regions and the potential pathogenicity of protein alterations. Here, we
      comprehensively evaluate the 3D spatial patterns of human germline and somatic
      variation in 6,604 experimentally derived protein structures and 33,144
      computationally derived homology models covering 77% of all human proteins. Using
      a systematic approach, we quantify differences in the spatial distributions of
      neutral germline variants, disease-causing germline variants, and recurrent
      somatic variants. Neutral missense variants exhibit a general trend toward
      spatial dispersion, which is driven by constraint on core residues. In contrast,
      germline disease-causing variants are generally clustered in protein structures
      and form clusters more frequently than recurrent somatic variants identified from
      tumor sequencing. In total, we identify 215 proteins with significant spatial
      constraints on the distribution of disease-causing missense variants in
      experimentally derived protein structures, only 65 (30%) of which have been
      previously reported. This analysis identifies many clusters not detectable from
      sequence information alone; only 12% of proteins with significant clustering in
      3D were identified from similar analyses of linear protein sequence. Furthermore,
      spatial analyses of mutations in homology-based structural models are highly
      correlated with those from experimentally derived structures, supporting the use
      of computationally derived models. Our approach highlights significant
      differences in the spatial constraints on different classes of mutations in
      protein structure and identifies regions of potential function within individual
      proteins.

PMID- 29455860
TI  - A Social-Interactive Neuroscience Approach to Understanding the Developing Brain.
AB  - From birth onward, social interaction is central to our everyday lives. Our
      ability to seek out social partners, flexibly navigate and learn from social
      interactions, and develop social relationships is critically important for our
      social and cognitive development and for our mental and physical health. Despite
      the importance of our social interactions, the neurodevelopmental bases of such
      interactions are underexplored, as most research examines social processing in
      noninteractive contexts. We begin this chapter with evidence from behavioral work
      and adult neuroimaging studies demonstrating how social-interactive context
      fundamentally alters cognitive and neural processing. We then highlight four
      brain networks that play key roles in social interaction and, drawing on existing
      developmental neuroscience literature, posit the functional roles these networks
      may play in social-interactive development. We conclude by discussing how a
      social-interactive neuroscience approach holds great promise for advancing our
      understanding of both typical and atypical social development.

PMID- 29455859
TI  - Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar
      Proteinosis with Hypogammaglobulinemia.
AB  - Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of a
      surfactant-like substance in alveolar spaces and hypoxemic respiratory failure.
      Genetic PAP (GPAP) is caused by mutations in genes encoding surfactant proteins
      or genes encoding a surfactant phospholipid transporter in alveolar type II
      epithelial cells. GPAP is also caused by mutations in genes whose products are
      implicated in surfactant catabolism in alveolar macrophages (AMs). We performed
      whole-exome sequence analysis in a family affected by infantile-onset PAP with
      hypogammaglobulinemia without causative mutations in genes associated with PAP:
      SFTPB, SFTPC, ABCA3, CSF2RA, CSF2RB, and GATA2. We identified a heterozygous
      missense variation in OAS1, encoding 2,'5'-oligoadenylate synthetase 1 (OAS1) in
      three affected siblings, but not in unaffected family members. Deep sequence
      analysis with next-generation sequencing indicated 3.81% mosaicism of this
      variant in DNA from their mother's peripheral blood leukocytes, suggesting that
      PAP observed in this family could be inherited as an autosomal-dominant trait
      from the mother. We identified two additional de novo heterozygous missense
      variations of OAS1 in two unrelated simplex individuals also manifesting
      infantile-onset PAP with hypogammaglobulinemia. PAP in the two simplex
      individuals resolved after hematopoietic stem cell transplantation, indicating
      that OAS1 dysfunction is associated with impaired surfactant catabolism due to
      the defects in AMs.

PMID- 29455861
TI  - Children's Developing Ideas About Knowledge and Its Acquisition.
AB  - We review key aspects of young children's concept of knowledge. First, we discuss
      children's early insights into the way that information can be communicated from
      informant to recipient as well as their active search for information via
      questions. We then analyze the way that preschool children talk explicitly and
      cogently about knowledge and the presuppositions they make in doing so. We argue
      that all children, irrespective of culture and language, eventually arrive at the
      same fundamental conception of knowledge in the preschool years. Nevertheless,
      despite the universality of this basic conception, young children are likely to
      show considerable variation in their pattern of information seeking, depending on
      the conversational practices of their family and culture.

PMID- 29455862
TI  - The Developmental Origins of Dehumanization.
AB  - Dehumanization is a complex social phenomenon, intimately connected to intergroup
      harm and neglect. However, developmental research has only recently started to
      investigate this important topic. In this chapter, we review research in areas
      closely related to dehumanization including children's intergroup preferences,
      essentialist conceptions of social groups, and understanding of relative status.
      We then highlight the small number of recent studies that have investigated the
      development of this social bias more directly. We close by making a series of
      suggestions for future research that will enable us to better understand the
      nature and causes of this harmful phenomenon.

PMID- 29455863
TI  - Trends and Divergences in Childhood Income Dynamics, 1970-2010.
AB  - Earnings and income variability have increased since the 1970s, particularly at
      the bottom of the income distribution. Considerable evidence suggests that
      childhood income levels-captured as average or point-in-time yearly income-are
      associated with numerous child and adult outcomes. The importance to child
      development of stable proximal processes during childhood suggests that income
      variability may also be important, particularly if it is unpredictable,
      unintentional, or does not reflect an upward trend in family income. Using the
      Panel Study of Income Dynamics, this study documents trends since the 1970s in
      three dimensions of childhood income dynamics: level, variability, and growth
      (n=7991). The analysis reveals that income variability during childhood has grown
      over time, while income growth rates have not. In addition, the economic context
      of childhood has diverged substantially by socioeconomic status, race, and family
      structure, with the most disadvantaged children facing a double-whammy of low
      income and high variability.

PMID- 29455865
TI  - Kin Networks and Mobility in the Transition to Adulthood.
AB  - Family support is critical for launching youth into successful adult lives.
      Although studies have documented the association between family support and
      success in the transition to young adulthood, existing work focuses primarily on
      parental support, giving little attention to extended kin. This narrow definition
      of family may miss critical exchanges of support, especially among low-income
      families. Drawing on panel survey data (n=450) and in-depth interviews (n=52)
      with young women from the Philadelphia Educational Longitudinal Study, this study
      expands our understanding of family support in the transition to adulthood by
      examining young adults' kin networks and the types of support and resources
      embedded within these networks. We find that kin support is an important buffer
      for those growing up in households without two biological parents, reducing the
      odds of perceiving oneself as an adult, having a child, and moving out.
      Qualitative data show that kin often step-in and play a parent-like role,
      providing needed instrumental and emotional support. Our results also highlight
      the complexity and fragility of kin network exchanges. While kin networks can be
      a source of resilience, they are often fragile and subject to external shocks,
      such as job loss and health declines. Moreover, kin networks can also be a source
      of obligation, delaying young adults' investments in their own educational
      trajectories. Those giving back to families are less likely to be in college
      compared to their peers and more likely to work, live independently, and consider
      themselves an adult.

PMID- 29455864
TI  - Social Influence on Positive Youth Development: A Developmental Neuroscience
      Perspective.
AB  - Susceptibility to social influence is associated with a host of negative outcomes
      during adolescence. However, emerging evidence implicates the role of peers and
      parents in adolescents' positive and adaptive adjustment. Hence, in this chapter
      we highlight social influence as an opportunity for promoting social adjustment,
      which can redirect negative trajectories and help adolescents thrive. We discuss
      influential models about the processes underlying social influence, with a
      particular emphasis on internalizing social norms, embedded in social learning
      and social identity theory. We link this behavioral work to developmental social
      neuroscience research, rooted in neurobiological models of decision making and
      social cognition. Work from this perspective suggests that the adolescent brain
      is highly malleable and particularly oriented toward the social world, which may
      account for heightened susceptibility to social influences during this
      developmental period. This chapter underscores the need to leverage social
      influences during adolescence, even beyond the family and peer context, to
      promote positive developmental outcomes. By further probing the underlying neural
      mechanisms as an additional layer to examining social influence on positive youth
      development, we will be able to gain traction on our understanding of this
      complex phenomenon.

PMID- 29455866
TI  - Cognition-Action Trade-Offs Reflect Organization of Attention in Infancy.
AB  - This chapter discusses what cognition-action trade-offs in infancy reveal about
      the organization and developmental trajectory of attention. We focus on internal
      attention because this aspect is most relevant to the immediate concerns of
      infancy, such as fluctuating levels of expertise, balancing multiple taxing
      skills simultaneously, learning how to control attention under variable
      conditions, and coordinating distinct psychological domains. Cognition-action
      trade-offs observed across the life span include perseveration during skill
      emergence, errors and inefficient strategies during decision making, and the
      allocation of resources when attention is taxed. An embodied cognitive-load
      account interprets these behavioral patterns as a result of limited attentional
      resources allocated across simultaneous, taxing task demands. For populations
      where motor errors could be costly, like infants and the elderly, attention is
      typically devoted to motor demands with errors occurring in the cognitive domain.
      In contrast, healthy young adults tend to preserve their cognitive performance by
      modifying their actions.

PMID- 29455867
TI  - Above and Beyond Objects: The Development of Infants' Spatial Concepts.
AB  - Early in development infants form categorical representations of small-scale
      spatial relations, such as left vs right and above vs below. This spatial skill
      allows infants to experience coherence in the layout of the objects in their
      environment and to note the equivalence of a spatial relation across changes in
      objects. Comparisons across studies of infant spatial categorization offer
      insight into the processes that contribute to the development of this skill.
      Rather than viewing contrasting results across studies as contradictory,
      identifying how infant spatial categorization tasks recruit distinct processes
      can not only reconcile findings but also yield insight into the starting points,
      development, and emerging nature of infants' representations of spatial
      relations. Also, situating infants' spatial categorization in the context of
      advances in nonspatial domains may reveal synergistic relations among these
      domains, particularly in relation to advances in infants' manipulative play with
      objects and their acquisition of spatial language. A central argument is that
      broadening the study of infants' spatial categorization may yield further
      insights into the nature of early spatial concepts and the processes that promote
      their development.

PMID- 29455868
TI  - Preface.

PMID- 29455870
TI  - Detection and incidence of Bordetella holmesii in respiratory specimens from
      patients with pertussis-like symptoms in New South Wales, Australia.
AB  - Bordetella pertussis, the aetiological agent of whooping cough is routinely
      diagnosed by polymerase chain reaction (PCR) directed at IS481, an insertion
      sequence target also found in Bordetella holmesii. Recent reports have suggested
      that B. holmesii infections can be misdiagnosed as pertussis, which can have a
      significant impact on public health surveillance. This study investigated the
      presence of B. holmesii in B. pertussis positive clinical samples, in order to
      determine the incidence of B. holmesii. Clinical cases of pertussis diagnosed by
      IS481-specific PCR between October 2008 and March 2016 in New South Wales were
      included. Bordetella holmesii was detected through the simultaneous amplification
      of IS481 and B. holmesii specific insertions sequence, hIS1001. A total of 46 of
      802 patients were identified to be positive for B. holmesii rather than B.
      pertussis, suggesting an incidence rate of 6.5% in 2009, 16.8% in 2010, 7.6%
      during 2013 and 8.1% during 2015. Bordetella holmesii infections were diagnosed
      during and between pertussis epidemics, however cases of B. holmesii and B.
      pertussis co-infections were not found. The predominant age group of B. holmesii
      infection was 11-18 years old, which was significantly different to the mean age
      of B. pertussis infections (0-6 years, p = 0.023). These findings revealed that
      B. holmesii was co-circulating alongside the B. pertussis epidemic for seven
      years, hidden from view, as B. holmesii infections have been diagnosed as B.
      pertussis. Confirmatory testing of B. pertussis positive samples for the presence
      of B. holmesii, especially during pertussis epidemics, should improve the quality
      of laboratory diagnosis and laboratory surveillance for pertussis. The presence
      of B. holmesii in Australia highlights the importance of testing for this
      pathogen and ongoing molecular surveillance that can guide the control of
      whooping cough.

PMID- 29455871
TI  - [Introduction to multidisciplinarity in neuro-oncology in Lebanon: First Annual
      Day of Neuro-Oncology].

PMID- 29455869
TI  - Overexpression of SLC1a5 in lymph node metastases outperforms assessment in the
      primary as a negative prognosticator in non-small cell lung cancer.
AB  - Despite recent advances in therapeutic options, lung cancer is the leading cause
      of death among malignant diseases worldwide. Glutamine-dependence is an
      established attribute in cancer tissue with emerging importance as a diagnostic
      and therapeutic target. We analysed the expression of SLC1a5, a major glutamine
      transporter, in the primary tumour and corresponding nodal metastasis of non
      small cell lung cancer (NSCLC) to investigate its biological impact. Expression
      of SLC1a5 was analysed by immunohistochemistry in 259 NSCLC and in 142 nodal
      metastases and correlated with clinicopathological parameters including overall
      survival. SLC1a5 expression in the primary tumour and in the corresponding lymph
      node metastasis revealed a positive correlation (p = 0.005). Moreover,
      overexpression of SLC1a5 was found to be an independent prognostic factor (p =
      0.027) if assessed in lymph node metastases only. SLC1A5 expression was studied
      for the first time in both primary NSCLC and its corresponding nodal metastasis.
      Our results indicate that overexpression of SLC1a5 is associated with shorter
      overall survival. This proved to be an independent prognosticator if assessed in
      the lymph node metastases. Thus, diagnostics in lymph node metastasis provide
      superior prognostic information for SLC1a5 overexpression and may open target
      prediction for future therapeutic options.

PMID- 29455872
TI  - [PD-L1 expression and PD-1/PD-L1 inhibitors in breast cancer].
AB  - The development of immune checkpoints inhibitors represents one of the major
      recent advances in oncology. Monoclonal antibodies directed against the
      programmed cell death protein 1 (PD-1) or its ligand (PD-L1) provides durable
      disease control, particularly in melanoma, lung, kidney, bladder and head and
      neck cancers. The purpose of this review is to synthesize current data on the
      expression of PD-L1 in breast cancer and on the preliminary clinical results of
      PD-1/PD-L1 inhibitors in breast cancer patients. In breast cancer, PD-L1
      expression is heterogeneous and is generally associated with the presence of
      tumor-infiltrating lymphocytes as well as the presence of poor-prognosis factors,
      such as young age, high grade, ER-negativity, PR-negativity, and HER-2
      overexpression, high proliferative index, and aggressive molecular subtypes
      (triple negative, basal-like, HER-2-overexpressing). Its prognostic value remains
      controversial when assessed with immunohistochemistry, whereas it seems favorable
      in triple-negative cancers when assessed at the mRNA level. Early clinical trials
      with PD-1/PD-L1 inhibitors in breast cancer have shown efficacy in terms of tumor
      response and/or disease control in refractory metastatic breast cancers, notably
      in the triple-negative subtype. Many trials are currently underway, both in the
      metastatic and neo-adjuvant setting. A crucial issue is identification of
      biomarkers predictive of response to PD-1/PD-L1 inhibitors.

PMID- 29455873
TI  - Prostatic Artery Chemoembolization-A Viable Management Option for Men Diagnosed
      with Prostate Cancer?

PMID- 29455858
TI  - A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior
      Identifies Multiple Significant Loci for Blood Pressure.
AB  - Genome-wide association analysis advanced understanding of blood pressure (BP), a
      major risk factor for vascular conditions such as coronary heart disease and
      stroke. Accounting for smoking behavior may help identify BP loci and extend our
      knowledge of its genetic architecture. We performed genome-wide association meta
      analyses of systolic and diastolic BP incorporating gene-smoking interactions in
      610,091 individuals. Stage 1 analysis examined ~18.8 million SNPs and small
      insertion/deletion variants in 129,913 individuals from four ancestries
      (European, African, Asian, and Hispanic) with follow-up analysis of promising
      variants in 480,178 additional individuals from five ancestries. We identified 15
      loci that were genome-wide significant (p < 5 * 10-8) in stage 1 and formally
      replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66
      additional genome-wide significant loci (13, 35, and 18 loci in European,
      African, and trans-ancestry, respectively). A total of 56 known BP loci were also
      identified by our results (p < 5 * 10-8). Of the newly identified loci, ten
      showed significant interaction with smoking status, but none of them were
      replicated in stage 2. Several loci were identified in African ancestry,
      highlighting the importance of genetic studies in diverse populations. The
      identified loci show strong evidence for regulatory features and support shared
      pathophysiology with cardiometabolic and addiction traits. They also highlight a
      role in BP regulation for biological candidates such as modulators of vascular
      structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8,
      RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic
      signaling (MSRA, EBF2).

PMID- 29455874
TI  - Utility of MR Angiography in the Identification of Prostatic Artery Origin Prior
      to Prostatic Artery Embolization.
AB  - In 17 patients who underwent prostate artery embolization for treatment of lower
      urinary tract symptoms, the accuracy of preprocedural magnetic resonance (MR)
      angiography was retrospectively compared with intraprocedural digital subtraction
      angiography (DSA) in the identification of prostatic artery origin. Of 34
      vessels, 26 MR angiography identified origins (76.5%) were confirmed by DSA at
      the time of embolization. Although image postprocessing is required, the ability
      of MR angiography to accurately identify prostatic artery origins prior to
      embolization is useful in treatment planning and can obviate the need for
      separate computed tomographic angiography, thus reducing both radiation dose and
      time demand on patients.

PMID- 29455875
TI  - Dieulefoy Lesion: Angiographic and Photographic Features with Pathologic
      Correlation.

PMID- 29455876
TI  - Laser Ablation Facilitates Closure of Chronic Enterocutaneous Fistulae.
AB  - This report describes the use of laser ablation for treatment of chronic
      enterocutaneous fistulae (ECFs) after failure of conservative therapy. Three
      patients underwent laser ablation for treatment of 8 ECFs. Mean duration of
      fistula patency was 28 months with mean fistula output of 134 mL/day. The initial
      technical success was 100% with no major or minor complications. Three ECFs
      required repeat treatment. At mean follow-up of 53 days, 7 of the fistulae were
      occluded. One fistula showed a markedly reduced output of 10 mL/day.

PMID- 29455877
TI  - Association of Vascular and Interventional Radiographers President's Message: A
      Call for Standardization in Technologist Education.

PMID- 29455878
TI  - Unusual Collateral Vascular Development in a Patient with Takayasu Arteritis.

PMID- 29455879
TI  - Transient and Regional Ischemia Related to Continuous Saline Solution Infusion
      during Radial Artery Access.
AB  - This case series illustrates a radial access complication seen in 7 of 9
      consecutive patients (age range, 44-53 y) undergoing uterine artery embolization
      in May and June 2017. Demonstrative images and videos identify a transient and
      clinically consequential skin ischemia caused by intraprocedural saline solution
      infusion through the occlusive radial artery sheath. All complications documented
      were classified as mild adverse events (class A) according to Society of
      Interventional Radiology criteria. Complication severity ranged from transient
      blanching to ischemic necrosis of the skin. Operator cognizance of this
      phenomenon with appropriate adjustment of saline solution infusion rates will
      prevent tissue ischemia and necrosis in radial access cases.

PMID- 29455880
TI  - Abscopal Effect after Radioembolization for Metastatic Breast Cancer in the
      Setting of Immunotherapy.

PMID- 29455881
TI  - Percutaneous Management of Peritoneovenous Shunt Malfunction in Children.

PMID- 29455882
TI  - Internal Jugular Vein Embolization to Control Life-Threatening Hemorrhage after
      Penetrating Neck Trauma.

PMID- 29455883
TI  - Disseminated Intravascular Coagulation and Acute Liver Injury from Ethanol
      Embolization of an Arteriovenous Malformation.

PMID- 29455884
TI  - Beta-2 Transferrin and IR.

PMID- 29455885
TI  - Vincristine resistance in relapsed neuroblastoma can be efficiently overcome by
      Smac mimetic LCL161 treatment.
AB  - PURPOSE: In spite of good initial therapy response neuroblastomas often spread to
      distant organs or relapse after periods of remission. Dysregulation of apoptosis,
      a hallmark of cancer, is often effected by elevated levels of antiapoptotic
      signals leading to resistance against chemotherapeutic drugs. Inhibitors of
      apoptosis proteins (IAPs) are crucial cellular apoptosis regulators. Targeting
      IAPs with Smac mimetics has been demonstrated as a promising strategy for
      treatment of neuroblastoma and other tumors. METHODS: In paired neuroblastoma
      cell lines, obtained from the same patient at time of diagnosis (CHLA-15) and
      postchemotherapy during progressive disease (CHLA-20), expression of crucial IAPs
      was determined. Furthermore, effects of vincristine on viability, cytotoxicity,
      apoptosis induction and caspase-3/7 activation were determined. RESULTS: Cellular
      IAP-1 (cIAP-1) and X-linked IAP (XIAP) expression was increased in cell line CHLA
      20. Moreover, biological effects of vincristine were significantly lower in these
      cells. Treatment of cells with Smac mimetic LCL161 increased the effects of
      vincristine in CHLA-15 cells and more importantly was able to overcome
      vincristine resistance in CHLA-20 cells. CONCLUSIONS: These findings demonstrate
      the potential of Smac mimetics for the development of novel therapeutic
      approaches for the treatment of relapsed/resistant neuroblastoma.

PMID- 29455886
TI  - Parental presence at induction of anesthesia: perceptions of a pediatric surgical
      department before and after program implementation.
AB  - INTRODUCTION: Parental presence at induction of general anesthesia (PPI) is
      highly desired by children and parents. However, it often faces resistance from
      medical personnel. We conducted a survey evaluating the perceptions of surgeons
      before and after establishment of a PPI program. METHODS: Internal web-based
      surveys using Likert Scale questions were administered to all members of a
      pediatric surgical department before and after the introduction of PPI at a
      freestanding children's hospital. Pre and post results were compared by Wilcoxon
      rank-sum tests. A p-value <=0.0026 was considered significant due to the
      Bonferroni correction. RESULTS: The survey was sent to 59 surgeons 1year before
      and 5years after gradual implementation of PPI. Response rates were 46% and 54%,
      pre and post implementation, respectively. After implementation, there was a
      statistically significant increased level of agreement with the statement: "PPI
      improves the parents' level of satisfaction" (p=0.0025) and a statistically
      significant decreased level of agreement with the statement "PPI lengthens the
      duration of induction" (p=0.0001). Before initiation, 56% wanted to see PPI
      implemented, while after implementation, 97% wanted PPI to remain. CONCLUSIONS: A
      majority of pediatric surgeons favored maintaining PPI after implementation.
      Resistance to initiation of PPI should not hinder implementation. TYPE OF STUDY:
      Survey LEVEL OF EVIDENCE: Not applicable.

PMID- 29455887
TI  - Nonlinear system identification based on Takagi-Sugeno fuzzy modeling and
      unscented Kalman filter.
AB  - This paper proposes two novel Kalman-based learning algorithms for an online
      Takagi-Sugeno (TS) fuzzy model identification. The proposed approaches are
      designed based on the unscented Kalman filter (UKF) and the concept of dual
      estimation. Contrary to the extended Kalman filter (EKF) which utilizes
      derivatives of nonlinear functions, the UKF employs the unscented transformation.
      Consequently, non-differentiable membership functions can be considered in the
      structure of the TS models. This makes the proposed algorithms to be applicable
      for the online parameter calculation of wider classes of TS models compared to
      the recently published papers concerning the same issue. Furthermore, because of
      the great capability of the UKF in handling severe nonlinear dynamics, the
      proposed approaches can effectively approximate the nonlinear systems. Finally,
      numerical and practical examples are provided to show the advantages of the
      proposed approaches. Simulation results reveal the effectiveness of the proposed
      methods and performance improvement based on the root mean square (RMS) of the
      estimation error compared to the existing results.

PMID- 29455888
TI  - Identification of process transfer function parameters in event-based PI control
      loops.
AB  - This paper presents a method to estimate the parameters of first and second order
      systems with time delays with different accuracy levels for autotuning of event
      based PI control loops. In particular, the event-based sampling condition applied
      in this work is based on the sampling strategy known as symmetric-send-on-delta
      (SSOD). The method is based on forcing the system to enter into a limit cycle and
      on using the information achieved from the oscillation to estimate the transfer
      function parameters. By manipulating the PI controller, the system can reach
      different limit cycles as a consequence of the intersections of the Nyquist map
      of the process with the describing function reciprocal of the event-based
      sampler. The frequency and amplitude of the limit cycle selected to apply the
      method define the quality of the estimations, avoiding the inaccuracy that relay
      identification methods based on describing function produce. Simulation results
      demonstrate that the estimations can be as accurate as those obtained with relay
      identification methods for time-driven control systems based on other approaches
      (state-space, curve fitting, Laplace transform, etc.).

PMID- 29455889
TI  - Design of an adaptive super-twisting decoupled terminal sliding mode control
      scheme for a class of fourth-order systems.
AB  - This paper proposes an adaptive super-twisting decoupled terminal sliding mode
      control technique for a class of fourth-order systems. The adaptive-tuning law
      eliminates the requirement of the knowledge about the upper bounds of external
      perturbations. Using the proposed control procedure, the state variables of cart
      pole system are converged to decoupled terminal sliding surfaces and their
      equilibrium points in the finite time. Moreover, via the super-twisting
      algorithm, the chattering phenomenon is avoided without affecting the control
      performance. The numerical results demonstrate the high stabilization accuracy
      and lower performance indices values of the suggested method over the other ones.
      The simulation results on the cart-pole system as well as experimental
      validations demonstrate that the proposed control technique exhibits a reasonable
      performance in comparison with the other methods.

PMID- 29455890
TI  - Passivity analysis of memristor-based impulsive inertial neural networks with
      time-varying delays.
AB  - This paper focuses on delay-dependent passivity analysis for a class of
      memristive impulsive inertial neural networks with time-varying delays. By
      choosing proper variable transformation, the memristive inertial neural networks
      can be rewritten as first-order differential equations. The memristive model
      presented here is regarded as a switching system rather than employing the theory
      of differential inclusion and set-value map. Based on matrix inequality and
      Lyapunov-Krasovskii functional method, several delay-dependent passivity
      conditions are obtained to ascertain the passivity of the addressed networks. In
      addition, the results obtained here contain those on the passivity for the
      addressed networks without impulse effects as special cases and can also be
      generalized to other neural networks with more complex pulse interference.
      Finally, one numerical example is presented to show the validity of the obtained
      results.

PMID- 29455891
TI  - Multi-objective path planning for unmanned surface vehicle with currents effects.
AB  - This paper investigates the path planning problem for unmanned surface vehicle
      (USV), wherein the goal is to find the shortest, smoothest, most economical and
      safest path in the presence of obstacles and currents, which is subject to the
      collision avoidance, motion boundaries and velocity constraints. We formulate
      this problem as a multi-objective nonlinear optimization problem with generous
      constraints. Then, we propose the dynamic augmented multi-objective particle
      swarm optimization algorithm to achieve the solution. With our approach, USV can
      select the ideal path from the Pareto optimal paths set. Numerical simulations
      verify the effectiveness of our formulated model and proposed algorithm.

PMID- 29455892
TI  - Synchronization of heterogeneous linear networks with distinct inner coupling
      matrices.
AB  - In this paper, we study synchronization of heterogeneous linear networks with
      distinct inner coupling matrices. Firstly, for synchronous networks, we show that
      any synchronous trajectory will converge to a corresponding synchronous state.
      Then, we provide an invariant set, which can be exactly obtained by solving
      linear equations and then used for characterizing synchronous states. Afterwards,
      we use inner coupling matrices and node dynamics to successively decompose the
      original network into a new network, composed of the external part and the
      internal part. Moreover, this new network can be proved to synchronize to the
      above invariant set by constructing the corresponding desired Lyapunov-like
      functions for the internal part and the external part respectively. In
      particular, this result still holds if the coupling strength is disturbed
      slightly. Finally, examples with numerical simulations are given to illustrate
      the validity and applicability of our theoretical results.

PMID- 29455893
TI  - Cognitive Behavioural Therapy for Insomnia (CBT-I) to treat depression: A
      systematic review.
AB  - INTRODUCTION: Major depressive disorder is one of the most commonly diagnosed
      psychiatric illnesses, and it has a profound negative impact on an individual's
      ability to function. Up to 90% of individuals suffering from depression also
      report sleep and circadian disruptions. If these disruptions are not effectively
      resolved over the course of treatment, the likelihood of relapse into depression
      is greatly increased. Cognitive Behavioural Therapy for Insomnia (CBT-I) has
      shown promise in treating these sleep and circadian disturbances associated with
      depression, and may be effective as a stand-alone treatment for depression. This
      may be particularly relevant in cases where antidepressant medications are not
      ideal (e.g. due to contraindications, cost, or treatment resistance). METHODS: A
      systematic literature review was conducted of trials investigating the use of CBT
      I to treat depression in adults. Therapy included in-person CBT-I, as well as
      telehealth and group CBT-I. RESULTS AND CONCLUSIONS: CBT-I presents a promising
      treatment for depression comorbid with insomnia. In-person therapy has the most
      supporting evidence for its efficacy, though treatment effects may not be
      additive with those of antidepressant medications. Insomnia improvement due to
      CBT-I may mediate the improvement in depressive symptoms. There is less evidence
      for the use of telehealth, though a stepped-care approach is indicated based on
      baseline depressive severity. More research on group therapy and telehealth
      modalities of delivering CBT-I are required before making recommendations.

PMID- 29455894
TI  - Cognitive behavioural therapy for MS-related fatigue explained: A longitudinal
      mediation analysis.
AB  - BACKGROUND: Cognitive behavioural therapy (CBT) effectively reduces fatigue
      directly following treatment in patients with Multiple Sclerosis (MS), but little
      is known about the process of change during and after CBT. DESIGN: Additional
      analysis of a randomized clinical trial. OBJECTIVE: To investigate which
      psychological factors mediate change in fatigue during and after CBT. METHODS:
      TREFAMS-CBT studied the effectiveness of a 16-week CBT treatment for MS-related
      fatigue. Ninety-one patients were randomized (44 to CBT, 47 to the MS-nurse
      consultations). Mediation during CBT treatment was studied using assessments at
      baseline, 8 and 16weeks. Mediation of the change in fatigue from post-treatment
      to follow-up was studied separately using assessments at 16, 26 and 52weeks.
      Proposed mediators were: changes in illness cognitions, general self-efficacy,
      coping styles, daytime sleepiness, concentration and physical activity, fear of
      disease progression, fatigue perceptions, depression and physical functioning.
      Mediators were separately analysed according to the product-of-coefficients
      approach. Confidence intervals were calculated with a bootstrap procedure.
      RESULTS: During treatment the decrease in fatigue brought on by CBT was mediated
      by improved fatigue perceptions, increased physical activity, less sleepiness,
      less helplessness, and improved physical functioning. Post-treatment increases in
      fatigue levels were mediated by reduced physical activity, reduced concentration,
      and increased sleepiness. CONCLUSION: These results suggests that focusing on
      improving fatigue perceptions, perceived physical activity, daytime sleepiness,
      helplessness, and physical functioning may further improve the effectiveness of
      CBT for fatigue in patients with MS. Maintenance of treatment effects may be
      obtained by focusing on improving physical activity, concentration and
      sleepiness.

PMID- 29455895
TI  - Childhood trauma and resilience in psoriatic patients: A preliminary report.
AB  - AIMS: Psoriasis is a chronic inflammatory skin disease with a complex etiology,
      involving the immune system, genetic factors, and external/internal triggers,
      with psychosomatic aspects. The aim of the study was to investigate childhood
      trauma and resilience in a psoriatic sample compared with healthy controls.
      Correlations between childhood trauma, resilience, quality of life, clinical data
      and psoriatic features were also evaluated. METHODS: Seventy-seven psoriatic
      patients and seventy-six homogeneous healthy controls were enrolled. We used the
      Psoriasis Area and Severity Index (PASI) to assess the severity of psoriasis and
      the Skindex-29 to measure health-related quality of life. The psychometric
      battery included the Childhood Trauma Questionnaire (CTQ) and the Connor-Davidson
      Resilience Scale (CD-Risc) to assess trauma exposure and resilience,
      respectively. RESULTS: Psoriatic patients showed a significant prevalence of
      childhood trauma and a lower resilience level compared to healthy controls.
      Associations between traumatic experiences, low resilience and reduced quality of
      life in psoriatic subjects were also observed. CONCLUSIONS: A multidisciplinary
      approach is helpful to investigate clinical aspects, trigger factors and
      psychophysiological stress response in psoriatic subjects. Improving resilience
      with an early psychological intervention focused on self-motivation and
      strengthening of self-efficacy could facilitate the management of psoriasis.

PMID- 29455896
TI  - Layered stigma? Co-occurring depression and obesity in the public eye.
AB  - OBJECTIVES: Obesity and depression are common conditions in the general public
      and show a high level of co-morbidity. Both conditions are stigmatized, i.e.,
      associated with negative attitudes and discrimination. Previous research shows
      that devalued conditions can overlap or combine to produce a layered stigma which
      is associated with more negative health outcomes than either single devalued
      condition alone. This study therefore set out to investigate the double stigma of
      obesity and depression. METHODS: A telephone-based representative study of the
      German population was conducted. Vignettes describing women with obesity,
      depression or both conditions were presented, followed by a set of items on
      semantic differentials based on previous stigma research of depression
      (depression stigma DS) and obesity (Fat Phobia Scale FPS). Personal experience
      with depression and obesity was assessed. RESULTS: All comparisons were
      significant in univariate ANOVA, showing negative attitudes measured by the FPS
      and the DS to be most pronounced in the double stigma condition. Multivariate
      analysis, controlling for age, gender, education and personal experience with the
      stigma condition (e.g. having obesity or depression), show that the double stigma
      obesity and depression is associated to more negative attitudes on the FPS
      (b=0.163, p<0.001) and the DS (b=0.154, p=0.002) compared to the single-stigma
      condition. CONCLUSIONS: The magnitude of the layered stigma of obesity and
      depression may need to be considered in mental health settings when treating the
      depressed patient with obesity, but likewise in obesity care when treating the
      obese patient with depression.

PMID- 29455897
TI  - Communal motivation in couples coping with vulvodynia: Sexual distress mediates
      associations with pain, depression, and anxiety.
AB  - OBJECTIVE: To examine the role of a novel motivational perspective-sexual
      communal motivation-in women's pain during intercourse and both partners'
      distress in couples coping with vulvodynia, a prevalent gynecological pain
      condition. Our goal was to test whether sexual communal strength (i.e.,
      motivation to meet a partner's sexual needs) and unmitigated sexual communion
      (i.e., prioritization of a partner's sexual needs in neglect of one's own needs)
      were indirectly associated with pain, depression, and anxiety via sexual
      distress. METHODS: Couples (N=101) completed daily surveys about their sexual
      communal motivation, sexual distress, anxiety, depression, and women reported on
      their pain during intercourse. Using multilevel modeling, we examined how daily
      fluctuations in sexual communal motivation were directly and indirectly (via
      sexual distress) associated with pain and psychological distress. RESULTS: On
      days when women with vulvodynia reported higher sexual communal strength, they
      reported less pain and anxiety, and on days when they reported higher unmitigated
      sexual communion, they reported more pain, more anxiety, and both partners
      reported more depressive symptoms. Daily associations between women's unmitigated
      sexual communion and greater pain, depression and anxiety were mediated by sexual
      distress. CONCLUSIONS: Being motivated to meet a partner's sexual needs was
      associated with less pain and anxiety for women with vulvodynia, but when this
      motivation excluded a focus on one's own needs, there were detrimental
      consequences for women's pain and both partners' depressive symptoms.
      Interventions for improving women's pain and the psychological well-being of
      affected couples should target motivational factors and sexual distress.

PMID- 29455898
TI  - Does emotional talk vary with fears of cancer recurrence trajectory? A content
      analysis of interactions between women with breast cancer and their therapeutic
      radiographers.
AB  - : Fears of cancer recurrence (FCR) in patients with breast cancer are
      hypothesised to develop over the period from diagnosis, through treatment and
      thereafter. A crucial point may be the contact that patients have with their
      therapeutic radiographer in review appointments. The study aimed to (1) describe
      and categorise the content of the identified emotional talk, and (2) consider the
      evidence for an association of content with FCR trajectory. METHODS: A concurrent
      mixed methods approach was applied as part of a larger investigation (FORECAST)
      of breast cancer patients (n=87). Patients completed a daily diary during their
      radiotherapy treatment. Audio recordings were collected of review appointments.
      The Verona Coding Definitions of Emotional Sequences (VR-CoDES) system was used
      to code patient emotional cues and concerns (CCs). Purposeful sampling of the
      daily diary ratings identified 12 patients (30 consultations) with an increasing
      (n=6) or decreasing (n=6) FCR trajectory. The emotional talk of these patients at
      their weekly reviews was content analysed. RESULTS: Four themes were identified
      from 185 CCs: Physical Symptoms, Factors External to Hospital, Treatment, and
      Labelling Cancer. FCR decreasing trajectory group consultations were longer
      (p<0.02), expressed twice as many CCs as the increasing trajectory group
      (p<0.001), and were more likely to refer to cancer directly (p<0.05).
      CONCLUSIONS: The emotional content expressed matched features outlined in the Lee
      Jones et al. (1997) FCR model, and showed evidence of avoidance in increasing FCR
      trajectory patients.

PMID- 29455899
TI  - Perception of induced dyspnea in fibromyalgia and chronic fatigue syndrome.
AB  - OBJECTIVE: Dyspnea perception is distorted in patients with medically unexplained
      dyspnea. The goals of this study were 1) to replicate these results in patients
      with fibromyalgia and/or chronic fatigue syndrome (CFS), and 2) to investigate
      predictors of distorted symptom perception within the patient group, with a focus
      on negative affectivity (NA), psychiatric comorbidity and somatic symptom
      severity. METHODS: Seventy-three patients diagnosed with fibromyalgia and/or CFS
      and 38 healthy controls (HC) completed a rebreathing paradigm, consisting of a
      baseline (60s of room air), a rebreathing phase (150s, gradually increasing
      ventilation, partial pressure of CO2 in the blood, and self-reported dyspnea),
      and a recovery phase (150s of room air). Dyspnea, respiratory flow and FetCO2
      levels were measured continuously. RESULTS: Patients reported more dyspnea than
      HC in the recovery phase (p=0.039), but no differences between patients and HC
      were found in the baseline (p=0.07) or rebreathing phase (p=0.17). No significant
      differences between patients and HC were found in physiological reactivity.
      Within the patient group, the effect in the recovery phase was predicted by
      somatic symptom severity (p=0.046), but not by negative affectivity or by the
      number of psychiatric comorbidities. CONCLUSION: This study extended earlier
      findings in patients with medically unexplained dyspnea to patients with
      fibromyalgia and CFS. This suggests that altered symptom perception is a non
      symptom-specific mechanism underlying functional somatic syndromes in general,
      particularly in patients with high levels of somatic symptom severity. The
      results are discussed in a predictive coding framework of symptom perception.

PMID- 29455900
TI  - Heart rate variability is associated with psychosocial stress in distinct social
      domains.
AB  - OBJECTIVE: Psychosocial stress is associated with substantial morbidity and
      mortality. Accordingly, there is a growing interest in biomarkers that indicate
      whether individuals show adaptive (i.e., stress-buffering and health-promoting)
      or maladaptive (i.e., stress-escalating and health-impairing) stress reactions in
      social contexts. As heart rate variability (HRV) has been suggested to be a
      biomarker of adaptive behavior during social encounters, it may be possible that
      inter-individual differences in HRV are associated with inter-individual
      differences regarding stress in distinct social domains. METHODS: To test this
      hypothesis, resting state HRV and psychosocial stress was assessed in 83 healthy
      community-dwelling individuals (age: 18-35years). HRV was derived from heart rate
      recordings during spontaneous and instructed breathing to assess the robustness
      of possible associations between inter-individual differences in HRV and inter
      individual differences in psychosocial stress. Psychosocial stress was determined
      with a self-report questionnaire assessing stress in distinct social domains.
      RESULTS: A series of categorical and dimensional analyses revealed an association
      between inter-individual differences in HRV and inter-individual differences in
      psychosocial stress: Individuals with high HRV reported less stress in social
      life, but not in family life, work life or everyday life, than individuals with
      low HRV. CONCLUSIONS: On basis of these findings, it may be assumed that
      individuals with high HRV experience less psychosocial stress than individuals
      with low HRV. Although such an assumption needs to be corroborated by further
      findings, it seems to be consistent with previous findings showing that
      individuals with high HRV suffer less from stress and stress-related disorders
      than individuals with low HRV.

PMID- 29455901
TI  - Prevalence of mental disorders and related functioning and treatment engagement
      among people with diabetes.
AB  - AIMS: To examine prevalence, functioning and treatment associated with all DSM-5
      12-month mood, anxiety, eating and substance use disorders among people with
      diabetes in data obtained from the National Epidemiologic Survey on Alcohol and
      Related Conditions-III. METHODS: Through multistage stratified randomized
      sampling a sample representative of the United States civilian population was
      obtained. Prevalence of diabetes (Type 1 and 2), DSM-5 disorders, physical and
      mental functioning, and treatment utilization were assessed via telephone
      interview. Analyses of weighted data (N=36,138) included calculation of
      descriptive statistics, and chi-square, logistic and linear regression analyses.
      RESULTS: Participants with (vs. without) diabetes (9.3% of weighted sample) had a
      significantly: (a) higher prevalence of any anxiety disorder and posttraumatic
      stress disorder (with and without adjustment for sociodemographic
      characteristics), and any mood disorder, major depressive disorder and specific
      phobia (with adjustment), (b) lower prevalence of any substance use disorder and
      alcohol and tobacco use disorders (with and without adjustment), and cannabis use
      disorder (without adjustment). Among participants with diabetes, mental disorder
      prevalence was consistently associated with sex and age, and to a lesser
      frequency, race/ethnicity. Lower levels of physical and mental functioning were
      found among participants with diabetes and a comorbid mental disorder. A minority
      of participants with diabetes and a comorbid mental disorder received treatment
      for mood and anxiety disorders, and few received treatment for eating and
      substance use disorders. CONCLUSIONS: Multiple types of mood, anxiety, eating and
      substance use disorders are prevalent, problematic, and often untreated among
      people with diabetes.

PMID- 29455902
TI  - Online social network response to studies on antidepressant use in pregnancy.
AB  - BACKGROUND: About 8% of U.S women are prescribed antidepressant medications
      around the time of pregnancy. Decisions about medication use in pregnancy can be
      swayed by the opinion of family, friends and online media, sometimes beyond the
      advice offered by healthcare providers. Exploration of the online social network
      response to research on antidepressant use in pregnancy could provide insight
      about how to optimize decision-making in this complex area. METHODS: For all 17
      research articles published on the safety of antidepressant use in pregnancy in
      2012, we sought to explore online social network activity regarding
      antidepressant use in pregnancy, via Twitter, in the 48h after a study was
      published, compared to the social network activity in the same period 1week prior
      to each article's publication. RESULTS: Online social network activity about
      antidepressants in pregnancy quickly doubled upon study publication. The
      increased activity was driven by studies demonstrating harm associated with
      antidepressants, lower-quality studies, and studies where abstracts presented
      relative versus absolute risks. IMPLICATIONS: These findings support a call for
      leadership from medical journals to consider how to best incentivize and support
      a balanced and clear translation of knowledge around antidepressant safety in
      pregnancy to their readership and the public.

PMID- 29455903
TI  - Gender differences in the relationship between workplace bullying and subjective
      back and neck pain: A two-wave study in a Norwegian probability sample.
AB  - OBJECTIVE: The association between exposure to bullying at work and subsequent
      pain reports is relatively well-established, but few studies have examined
      possible moderators of this relationship. As gender is a known risk factor for
      pain, with women reporting pain levels of higher intensity and longer duration, a
      possible gender difference in the relationship between bullying and pain has been
      suggested, but not sufficiently tested. The objective of the present study was
      therefore to examine whether gender moderates the prospective relationship
      between exposure to workplace bullying behaviours and subsequent subjective back
      and neck pain. METHODS: A national probability sample of Norwegian workers
      (N=1003) was collected at two time points with a six-month time-lag. Assumptions
      were tested using regression and moderation analyses. RESULTS: Exposure to
      bullying behaviours was associated with increased reports of subjective back and
      neck pain over time, and this relationship was moderated by gender. However, the
      interaction took a different form than expected, with back and neck pain
      increasing in response to bullying among men only, to a degree that nullified the
      baseline gender difference. CONCLUSION: The assumption that being female is a
      vulnerability factor for the development of pain in the aftermath of psychosocial
      stressors such as bullying was contradicted in the present study. Instead,
      women's relatively high baseline pain levels remain stable over time even after
      exposure to workplace bullying, while men's relatively low baseline pain levels
      increase in response to bullying, ultimately becoming tangent to the pain
      reported by women.

PMID- 29455904
TI  - Hypoglossal nerve paralysis in a child after a dental procedure.
AB  - Unilateral palsy of the hypoglossal nerve is a rare complication of orthodontic
      procedures. The main reported causes of HNP are: orthopedic and
      otorhinolaryngology surgical interventions, and in particular maneuvers involving
      compression or overstretching of the hypoglossal nerve, dental procedures and
      traumas, and also infections, motoneuron disorders, tumors, vascular diseases.
      Diagnosis is usually performed by electrophysiology studies (EMG-VCN), and brain
      magnetic resonance imaging (MRI) is useful to exclude other causes. The prognosis
      depends on the location and extension of the damage. Currently there is not a
      standardized treatment approach except the speech therapy, although, in some
      cases, the high-dose steroid treatment could be useful. We describe the case of a
      ten-year-old female, who was admitted in our Unit after a deviation of the tongue
      associated with dysarthria and dysphagia, occurred after the application of a
      mobile orthodontic device.

PMID- 29455905
TI  - Ventriculoperitoneal shunt treatment in a pregnant renal transplant recipient
      with idiopathic intracranial hypertension: Case report and review of the
      literature.
AB  - Idiopathic intracranial hypertension (IIH) is a relatively uncommon disorder
      characterised by raised intracranial pressure without an established
      pathogenesis. Diagnosis of IIH requires the demonstration of symptoms and signs
      referable only to elevated intracranial pressure; cerebrospinal fluid (CSF)
      opening pressure >25cm H2O measured in the lateral decubitus position; normal CSF
      composition; and no evidence for an underlying structural cause demonstrated by
      using MRI or contrast-enhanced CT scan for typical patients and MRI and MR
      venography for atypical patients such as man, children and those with low body
      mass index. We present a 38-year old primigravid renal transplant patient at 7
      weeks of gestation who presented with 2 weeks of intense, throbbing, holocranial
      headache, nausea, vomiting, photophobia, diplopia and progressive visual loss.
      When medical treatment fails and/or not appropriate to use due to the reported of
      teratogenic risks in pregnant women, surgical interventions gain importance. In
      this particular patient, venticuloperitoneal shunt was chosen as the CSF
      diversion technique. In this case report indications, contraindications in
      addition to outcomes regarding headache, vision loss and the resolution of
      papilloedema of the present surgery options for IIH are discussed.

PMID- 29455906
TI  - Clinical analysis of combined revascularization in treating ischemic Moyamoya
      disease in adults.
AB  - OBJECTIVE: The aim of this study was to investigate the clinical efficacy of
      superficial temporal artery-middle cerebral artery anastomosis (STA
      MCA)+encephalo-duro-myo-synangiosis (EDMS) in treating ischemic Moyamoya disease
      (IMD) in adults. METHODS: A total of 30 adult patients with IMD were selected to
      be included in the study; they underwent STA-MCA+EDMS and were followed up for 3
      months to 2 years. The digital subtraction angiography findings, modified Rankin
      scale (mRs) score, and complications of all the patients were compared. RESULTS:
      Thirty patients successfully completed the surgery. Three patients had
      postoperative complications (two patients with cerebral infarction on the
      surgical side and one patient with poor scalp healing). The postoperative
      morbidity rate was 10%. Angiography conducted at 3 to 6 months postoperatively
      showed 28 cases of anastomotic patency; the anastomotic patency rate was 93.3%.
      The mRs scores of the patients' neurological function 3 months after surgery were
      lower than those before surgery. CONCLUSION: STA-MCA+EDMS is effective in
      treating Moyamoya disease.

PMID- 29455907
TI  - Introduction to a Seminar on implementation and de-implementation to improve
      urologic cancer care.

PMID- 29455908
TI  - Increased degradation of ATP is driven by memory regulatory T cells in kidney
      transplantation tolerance.
AB  - Regulatory T cells were recently proposed as the central actor in operational
      tolerance after renal transplantation. Tolerant patients harbor increased FoxP3hi
      memory Treg frequency and increased demethylation in the Foxp3 Treg-specific
      demethylated region when compared to stable kidney recipients and exhibit greater
      memory Treg suppressive capacities and higher expression of the ectonucleotidase
      CD39. However, in this particular and unique situation the mechanisms of action
      of Tregs were not identified. Thus, we analyzed the ability of memory Tregs to
      degrade extracellular ATP in tolerant patients, healthy volunteers, and patients
      with stable graft function under immunosuppression and determined the role of
      immunosuppressive drugs on this process. The conserved proportion of memory Tregs
      leads to the establishment of a pro-tolerogenic balance in operationally tolerant
      patients. Memory Tregs in tolerant patients display normal capacity to degrade
      extracellular ATP/ADP. In contrast, memory Tregs from patients with stable graft
      function do not have this ability. Finally, in vitro, immunosuppressive drugs may
      favor the lower proportion of memory Tregs in stable patients, but they have no
      effect on CD39-dependent ATP degradation and do not explain memory Treg lack of
      extracellular ATP/ADP degradation ability. Thus, intrinsic active regulatory
      mechanisms may act long after immunosuppressive drug arrest in operationally
      tolerant patients and may contribute to kidney allograft tolerance via the
      maintenance of CD39 Treg function.

PMID- 29455909
TI  - Elevated tissue sodium deposition in patients with type 2 diabetes on
      hemodialysis detected by 23Na magnetic resonance imaging.
AB  - Long-term elevated blood sugar levels result in tissue matrix compositional
      changes in patients with diabetes mellitus type 2 (T2DM). We hypothesized that
      hemodialysis patients with T2DM might accumulate more tissue sodium than control
      hemodialysis patients. To test this, 23Na magnetic resonance imaging (23Na MRI)
      was used to estimate sodium in skin and muscle tissue in hemodialysis patients
      with or without T2DM. Muscle fat content was estimated by 1H MRI and tissue
      sodium content by 23Na MRI pre- and post-hemodialysis in ten hemodialysis
      patients with T2DM and in 30 matched control hemodialysis patients. We also
      assessed body fluid distribution with the Body Composition Monitor. 1H MRI
      indicated a tendency to higher muscle fat content in hemodialysis patients with
      T2DM compared to non-diabetic hemodialysis patients. 23Na MRI indicated increased
      sodium content in muscle and skin tissue of hemodialysis patients with T2DM
      compared to control hemodialysis patients. Multi-frequency bioimpedance was used
      to estimate extracellular water (ECW), and excess ECW in T2DM hemodialysis
      patients correlated with HbA1c levels. Sodium mobilization during hemodialysis
      lowered muscle sodium content post-dialysis to a greater degree in T2DM
      hemodialysis patients than in control hemodialysis patients. Thus, our findings
      provide evidence that increased sodium accumulation occurs in hemodialysis
      patients with T2DM and that impaired serum glucose metabolism is associated with
      disturbances in tissue sodium and water content.

PMID- 29455910
TI  - A public health needs assessment for domestic indoor overheating.
AB  - OBJECTIVES: Indoor overheating is a potentially fatal health hazard that was
      identified as an issue requiring urgent action in the 2017 UK Climate Change Risk
      Assessment. We aimed to make research on this issue more accessible to local
      public health teams to encourage its inclusion in local strategic needs
      assessments. STUDY DESIGN: Epidemiological health needs assessment. METHODS: We
      adapted established health needs assessment methods, focussing on the
      epidemiological component, drawing evidence from a non-systematic literature
      review that was complemented by discussion with experts. RESULTS: Indoor
      overheating arises from an interaction between occupants' susceptibility to heat,
      their behaviour and the building's location and its characteristics. Many of
      these factors are interrelated and, at a national level, are expected to vary
      over time with demographic and climate change. Understanding these factors, ways
      to mitigate them and a long-term view are all essential for managing overheating
      risk. CONCLUSIONS: There is a need for services to be provided at the local level
      that consider the home environment and its impact on health in all seasons. A
      population-level approach to risk management across a local area is also useful
      to inform collaborative efforts to reduce future incidence of overheating and
      better understand how it varies with socio-economic deprivation.

PMID- 29455911
TI  - Trauma theatre productivity - Does the individual surgeon, anaesthetist or
      consultant presence matter?
AB  - INTRODUCTION: With rising NHS clinical and financial demands, improving theatre
      efficiency is essential to maintain quality of patient care. Consistent teams and
      consultant presence have been shown to improve outcomes and productivity in
      elective orthopaedic surgery. The aim of this study was to investigate the impact
      on trauma theatre productivity of different surgeons and anaesthetists working
      together in a Major Trauma Centre. The influence of consultant presence and
      weekend operating on productivity was also considered. METHODS: Data relating to
      a single orthopaedic trauma theatre was gathered retrospectively for a two-year
      period. Variables including orthopaedic and anaesthetic consultant presence,
      number and complexity of operations performed and procedure start times were
      collected for daily trauma lists. Individual anaesthetic and orthopaedic
      consultants were compared by productivity outcomes. The impact of surgeons
      operating more frequently with one anaesthetist was also examined. RESULTS: Data
      relating to 2384 patients undergoing a total of 2787 procedures was collected.
      Orthopaedic consultant presence at the first surgical case (p < 0.05) and for 50%
      or greater of cases (p < 0.05) lead to higher mean number of cases performed per
      list and reduced turnaround time. Despite working with a significantly higher
      number of different consultant anaesthetists (p < 0.001) in year two, the
      productivity of surgeons as judged by list start time, total cases per list and
      total operating time was not significantly affected. Significantly earlier start
      times (p < 0.001) and shorter turnaround times (p < 0.001) at weekends led to
      maintained productivity despite shorter theatre time. No significant difference
      in productivity was found when comparing individual anaesthetic and orthopaedic
      consultants. Productivity was not significantly increased by surgeons operating
      more frequently with one individual anaesthetist. CONCLUSION: In the setting of
      an acute trauma theatre, orthopaedic consultant presence led to increased
      productivity. Furthermore, individual surgeon and anaesthetist pairings had no
      effect on overall productivity. Future efforts to improve productivity should
      focus on achieving earlier start times, consultant supervision of lists and
      reduced turnaround times between cases.

PMID- 29455912
TI  - Unperturbed, high spatial resolution measurement of Radon-222 in soil-gas depth
      profile.
AB  - This work presents a method for measuring the depth distribution of 222Rn
      activity in soil gas. The method is based on the capacity of polycarbonates to
      absorb 222Rn and on the possibility of performing sensitive measurements of 222Rn
      absorbed by the polycarbonates via liquid scintillation counting (LSC). The
      method is the following: cylindrical holes are drilled along a metal rod and
      Makrofol(r) N polycarbonate foils enclosed in polyethylene envelopes are placed
      in each hole. The rod is driven into the soil and kept for a certain time. As
      long as the rod is in the soil, the polycarbonate foils are exposed to the 222Rn
      concentration at their depth. At the end of the exposure the rod is pulled out
      and the foils are transferred to liquid scintillation (LS) vials filled with
      liquid scintillator. The 222Rn absorbed in the foils is then measured with a LS
      analyzer. The rod with the polycarbonate foils acts as a passive probe which
      senses the 222Rn concentration at different depths beneath the ground surface.
      The achievable minimum detectable 222Rn activity concentration with the equipment
      and conditions used in this study is around 12.5 kBq/m3. It can easily be lowered
      below 1 kBq/m3 if larger foils and low-background LS analyzers are used. Since
      the method does not require air sampling the depth distribution of 222Rn in the
      soil is unperturbed by the sampling. The spatial distribution and the maximum
      measurement depth are set by the distance between the holes and the depth to
      which the rod can be fixed into the ground. Results from in situ applications of
      the method in terrains with high 222Rn in soil-gas are reported, which
      demonstrate the feasibility and the usefulness of the proposed approach.

PMID- 29455913
TI  - Significant reduction in indoor radon in newly built houses.
AB  - Results from two national surveys of radon in newly built homes in Norway,
      performed in 2008 and 2016, were used in this study to investigate the effect of
      the 2010 building regulations introducing limit values on radon and requirements
      for radon prevention measures upon construction of new buildings. In both
      surveys, homes were randomly selected from the National Building Registry. The
      overall result was a considerable reduction of radon concentrations after the
      implementation of new regulations, but the results varied between the different
      dwelling categories. A statistically significant reduction was found for detached
      houses where the average radon concentration was almost halved from 76 to 40
      Bq/m3. The fraction of detached houses which had at least one frequently occupied
      room with a radon concentration above the Action Level (100 Bq/m3) fell from
      23.9% to 6.4%, while the fraction above the Upper Limit Value (200 Bq/m3) was
      reduced from 7.6% to 2.5%. In 2008 the average radon concentration measured in
      terraced and semi-detached houses was 44 and in 2016 it was 29 Bq/m3, but the
      reduction was not statistically significant. For multifamily houses, it was not
      possible to draw a conclusion due to insufficient number of measurements.

PMID- 29455914
TI  - Novel spectrometers for environmental dose rate monitoring.
AB  - A new generation of dosemeters, based on the scintillators LaBr3, CeBr3 and SrI2,
      read out with conventional photomultipliers, to be used in the field of
      environmental gamma-radiation monitoring, was investigated. The main features of
      these new instruments and especially their outdoor performance, studied by long
      term investigations under real weather conditions, are presented. The systems
      were tested at the reference sites for environmental radiation of the
      Physikalisch-Technische Bundesanstalt. The measurements are compared with that of
      well characterized classical dose rate reference instruments to demonstrate the
      suitability of new spectrometers for environmental dose rate monitoring even in
      adverse weather conditions. Their potential to replace the (mainly Geiger Muller
      based) dose rate meters operated in about 5000 European early waning network
      stations as well as in environmental radiation monitoring in general is shown.

PMID- 29455915
TI  - Fatty acid composition, enzyme activities and metallothioneins in Donax trunculus
      (Mollusca, Bivalvia) from polluted and reference sites in the Gulf of Annaba
      (Algeria): Pattern of recovery during transplantation.
AB  - The gulf of Annaba, the most important touristic and economic coastal zone
      located in Northeast Algeria, is contaminated by several pollutants from urban,
      agricultural, harbor and industrial activities. Elevated levels of heavy metals
      were detected in a locally prevalent edible mollusk Donax trunculus (Bivalvia,
      Donacidae) widely used as a sentinel species for the assessment of marine
      pollution. The present work aims to measure the difference between two
      localities, one being full of different pollutants (Sidi Salem) and the other
      being relatively clean (El Battah) and to evaluate the ability of D. trunculus to
      overcome the environmental stress during a transplantation experiment by a
      determination of fatty acid profile, the enzymes activities and the level of
      metallothioneins (MTs), a biomarker of metallic contamination. Adults of D.
      trunculus were collected at Sidi Salem (contaminated site) and transplanted into
      El Battah (reference site) for 21 days in cages (60 * 60 * 60 cm with a 2 mm
      mesh). Biochemical analyzes were conducted at different times (0, 7, 14 and 21
      days). At 0-day experiment: the rate of the fatty acids, the enzymes activities
      and MT levels at the site of Sidi Salem (polluted site) were significantly
      different from those of El Battah. During the transplantation a gradual
      restoration of fatty acids rates, enzymes activities and MT levels was observed.
      At the end of the period of transplantation, the values are comparable to those
      of El Battah. A two-way ANOVA (time, site) on data revealed significant effects
      of time and site. Overally, D. trunculus is able to induce its detoxification
      system and to restore relatively rapidly the status of individuals from the
      reference site (El Battah).

PMID- 29455916
TI  - Mobilisation kinetics of hazardous elements in marine plastics subject to an
      avian physiologically-based extraction test.
AB  - Samples of plastic collected from two beaches in southwest England (n = 185) have
      been analysed by XRF spectrometry for elements that are hazardous or restricted
      in synthetic polymers (namely, As, Ba, Br, Cd, Cr, Hg, Pb, Sb and Se). Overall,
      one or more restricted element was detected in 151 samples, with 15 cases
      exhibiting non-compliance with respect to the Restriction of Hazardous Substances
      (RoHS) Directive. Twelve plastics that were RoHS-non-compliant were subsequently
      processed into microplastic-sized fragments and subjected to an avian
      physiologically-based extraction test (PBET) that simulates the chemical
      conditions in the gizzard-proventriculus of the northern fulmar. Kinetic profiles
      of metal and metalloid mobilisation in the PBET were fitted using a pseudo-first
      order diffusion model with rate constants ranging from ~0.02 to 0.5 h-1, while
      profiles for Br were better fitted with a parabolic diffusion model and rate
      constants of 7.4-9.5 (MUg L-1)-1h-1/2. Bioaccessibilities, based on maximum or
      equilibrium concentrations mobilised relative to total (XRF) concentrations,
      ranged from <1% for Cd and Se in polyethylene and polypropylene to over 10% for
      Br in a sample of expanded polystyrene and Pb in a sample of PVC. Calculations
      suggest that ingested plastic could contribute about 6% and 30% of a seabird's
      exposure to and accumulation of Pb and brominated compounds, respectively.

PMID- 29455917
TI  - Respiratory hazard assessment of combined exposure to complete gasoline exhaust
      and respirable volcanic ash in a multicellular human lung model at the air-liquid
      interface.
AB  - Communities resident in urban areas located near active volcanoes can experience
      volcanic ash exposures during, and following, an eruption, in addition to
      sustained exposures to high concentrations of anthropogenic air pollutants (e.g.,
      vehicle exhaust emissions). Inhalation of anthropogenic pollution is known to
      cause the onset of, or exacerbate, respiratory and cardiovascular diseases. It is
      further postulated similar exposure to volcanic ash can also affect such disease
      states. Understanding of the impact of combined exposure of volcanic ash and
      anthropogenic pollution to human health, however, remains limited. The aim of
      this study was to assess the biological impact of combined exposure to respirable
      volcanic ash (from Soufriere Hills volcano (SHV), Montserrat and Chaiten volcano
      (ChV), Chile; representing different magmatic compositions and eruption styles)
      and freshly-generated complete exhaust from a gasoline vehicle. A multicellular
      human lung model (an epithelial cell-layer composed of A549 alveolar type II-like
      cells complemented with human blood monocyte-derived macrophages and dendritic
      cells cultured at the air-liquid interface) was exposed to diluted exhaust (1:10)
      continuously for 6 h, followed by immediate exposure to the ash as a dry powder
      (0.54 +/- 0.19 MUg/cm2 and 0.39 +/- 0.09 MUg/cm2 for SHV and ChV ash,
      respectively). After an 18 h incubation, cells were exposed again for 6 h to
      diluted exhaust, and a final 18 h incubation (at 37  degrees C and 5% CO2). Cell
      cultures were then assessed for cytotoxic, oxidative stress and (pro
      )inflammatory responses. Results indicate that, at all tested (sub-lethal)
      concentrations, co-exposures with both ash samples induced no significant
      expression of genes associated with oxidative stress (HMOX1, NQO1) or production
      of (pro-)inflammatory markers (IL-1beta, IL-8, TNF-alpha) at the gene and protein
      levels. In summary, considering the employed experimental conditions, combined
      exposure of volcanic ash and gasoline vehicle exhaust has a limited short-term
      biological impact to an advanced lung cell in vitro model.

PMID- 29455918
TI  - Consistent patterns of debris on South African beaches indicate that industrial
      pellets and other mesoplastic items mostly derive from local sources.
AB  - Identifying the sources of small plastic fragments is challenging because the
      original source item seldom can be identified. South Africa provides a useful
      model system to understand the factors influencing the distribution of beach
      litter because it has an open coastline with four equally-spaced urban-industrial
      centres distant from other major source areas. We sampled mesodebris (~2-25 mm)
      at 82 South African beaches in 1994, 2005 and 2015. Plastic items comprised 99%
      by number and 95% by mass of litter items. Industrial pellets were the most
      abundant plastic items, but fragments of rigid plastic items comprised most of
      the mass of debris. Strong correlations between industrial pellets and other
      plastic items indicate that common factors influence the distribution of both
      pellets and secondary mesoplastics. The abundance of mesodebris at beaches also
      was correlated in successive surveys, suggesting that beach-specific factors
      (e.g. aspect, slope, local currents, etc.) influence the amounts of debris on
      each beach. Sample year had no effect on mesodebris abundance, indicating that
      there has been little change in the amounts of mesodebris over the last two
      decades. There were consistently higher densities of both industrial pellets and
      other plastic items at beaches close to urban-industrial centres; there were only
      weak correlations with human population density and no correlation with local
      runoff. The size of industrial pellets decreased away from local urban centres,
      further supporting the conclusion that, like macroplastic litter, most
      mesoplastic pollution on continental beaches derives from local, land-based
      sources. This finding means that local actions to reduce plastics entering the
      sea will have local benefits, and that it may be possible to assess the efficacy
      of mitigation measures to reduce marine inputs of mesoplastic items.

PMID- 29455919
TI  - Satellite-based high-resolution PM2.5 estimation over the Beijing-Tianjin-Hebei
      region of China using an improved geographically and temporally weighted
      regression model.
AB  - Ground fine particulate matter (PM2.5) concentrations at high spatial resolution
      are substantially required for determining the population exposure to PM2.5 over
      densely populated urban areas. However, most studies for China have generated
      PM2.5 estimations at a coarse resolution (>=10 km) due to the limitation of
      satellite aerosol optical depth (AOD) product in spatial resolution. In this
      study, the 3 km AOD data fused using the Moderate Resolution Imaging
      Spectroradiometer (MODIS) Collection 6 AOD products were employed to estimate the
      ground PM2.5 concentrations over the Beijing-Tianjin-Hebei (BTH) region of China
      from January 2013 to December 2015. An improved geographically and temporally
      weighted regression (iGTWR) model incorporating seasonal characteristics within
      the data was developed, which achieved comparable performance to the standard
      GTWR model for the days with paired PM2.5- AOD samples (Cross-validation (CV) R2
      = 0.82) and showed better predictive power for the days without PM2.5- AOD pairs
      (the R2 increased from 0.24 to 0.46 in CV). Both iGTWR and GTWR (CV R2 = 0.84)
      significantly outperformed the daily geographically weighted regression model (CV
      R2 = 0.66). Also, the fused 3 km AODs improved data availability and presented
      more spatial gradients, thereby enhancing model performance compared with the
      MODIS original 3/10 km AOD product. As a result, ground PM2.5 concentrations at
      higher resolution were well represented, allowing, e.g., short-term pollution
      events and long-term PM2.5 trend to be identified, which, in turn, indicated that
      concerns about air pollution in the BTH region are justified despite its
      decreasing trend from 2013 to 2015.

PMID- 29455920
TI  - Operating room traffic in total joint arthroplasty: Identifying patterns and
      training the team to keep the door shut.
AB  - BACKGROUND: Surgical site infections after joint arthroplasty are devastating
      complications and are influenced by patient, surgical, and operating room
      environmental factors. METHODS: In an effort to reduce the incidence of door
      openings (DOs) during total joint arthroplasty cases, this prospective
      observational study consisted of 3 phases. Phase 1 determined the baseline
      incidence of DOs, followed by installation of a mechanical door counter (phase
      2). Finally, an educational seminar was presented to all personnel (phase 3)
      regarding the implications frequent DOs have on patient and surgical outcomes.
      RESULTS: The average openings per case (OPC) for each of the 3 phases were 33.5,
      34.2, and 27.7, respectively. There was a 17% reduction in OPC between phases 1
      and 3 (P= .02). There were no significant differences between knee and hip
      arthroplasty cases during the 3 phases (P= .21, P= .46, and P= .81,
      respectively). There was a strong correlation between length of surgery and OPC,
      with a Pearson coefficient of r = 0.87 during phase 3. To account for differences
      in average operative time between phases, data were normalized for the length of
      surgery with the ratio of door openings per minute determined (0.36, 0.34, and
      0.32 for each phase, respectively). CONCLUSIONS: We were able to show that simply
      monitoring door openings during joint arthroplasty was not effective in reducing
      the occurrences. However, after a novel educational seminar given to all
      personnel, we were able to significantly reduce the incidence of operating room
      door openings, reducing a potential risk factor for surgical site infections.

PMID- 29455921
TI  - Clinical and epidemiological characteristics of intestinal parasite infection by
      Blastocystis hominis.
AB  - OBJECTIVES: Blastocystis hominis (B. hominis) is one of the most common
      intestinal parasites isolated in humans. The parasite can cause gastrointestinal
      symptoms or, in most cases, remain asymptomatic. There are issues concerning the
      parasite's pathogenic character. The aim of this study was to analyse the
      clinical and epidemiological characteristics of the parasite infection by B.
      hominis, with or without other parasitic co-infections. PATIENTS AND METHODS: An
      observational retrospective study was conducted of B. hominis isolates in faeces
      from October 2004 to March 2016 in a tropical medicine unit. We reviewed all
      patients with a parasite infection, exclusively or not by B. hominis. RESULTS: We
      studied 3070 patients, 570 (18%) of whom were diagnosed with B. hominis
      infection, which was the only isolate in 245 (43%) of the 570 patients. A total
      of 325 (57%) patients presented other parasitic co-infections (Entamoeba
      histolytic or Entamoeba dispar, Strongyloides stercoralis, hookworm and
      Schistosoma spp.). The main symptom was abdominal pain (41.8%). In 31.2% of
      cases, the parasite was detected in the imported diseases screening of
      asymptomatic patients. Of those who underwent treatment with metronidazole, 78.2%
      improved. The parasite was neutralised in 82.6% of the patients. CONCLUSIONS:
      Parasite infection by B. hominis is one of the most common diseases in our
      tropical medicine unit. Most patients are asymptomatic, or their symptoms can be
      attributed to other parasite infections. In those cases in which symptoms persist
      without being able to attribute them to other causes, a specific treatment is
      recommended.

PMID- 29455922
TI  - Corrigendum to "Do prolonged grief disorder symptoms predict post-traumatic
      stress disorder symptoms following bereavement? A cross-lagged analysis" [Compr
      Psychiatry 80 (2018) 65-71].

PMID- 29455923
TI  - Prevalence, Location, and Characteristics of Chronic Pain in Intensive Care
      Survivors.
AB  - BACKGROUND: A growing number of studies have addressed the long-term consequences
      of intensive care unit (ICU) treatment, but few have studied the prevalence of
      chronic pain and pain characteristics longitudinally. AIMS: The goal of the work
      described here was to investigate the prevalence and characteristics of chronic
      pain in ICU survivors 3 months and 1 year after ICU discharge and to identify
      risk factors for chronic pain 1 year after ICU discharge. DESIGN: The design used
      was an explorative and longitudinal study. SETTING/PATIENTS: The patients in this
      work had stayed >48 hours in two mixed ICUs in Oslo University Hospital, a
      tertiary referral hospital. METHODS: Patients completed a survey questionnaire 3
      months and 1 year after ICU discharge. Pain was assessed using the Brief Pain
      Inventory-Short Form. RESULTS: At 3 months after discharge, 58 of 118 ICU
      survivors (49.2%) reported pain, and at 1 year after discharge, 34 of 89
      survivors (38.2%) reported pain. The most common sites of pain at 3 months were
      the shoulder and abdomen; the shoulder remained the second most common site at 1
      year. There was an increase in the interference of pain with daily life at 1
      year. Possible risk factors for chronic pain at 1 year were increased severity of
      illness, organ failure, ventilator time >12 days, and ICU length of stay >15
      days. The most common sites of pain were not linked to the admission diagnosis.
      CONCLUSIONS: These findings may enable health care providers to improve care and
      rehabilitation for this patient group.

PMID- 29455924
TI  - GEC-ESTRO ACROP recommendations in skin brachytherapy.
AB  - PURPOSE: The aim of this publication is to compile available literature data and
      expert experience regarding skin brachytherapy (BT) in order to produce general
      recommendations on behalf of the GEC-ESTRO Group. METHODS: We have done an
      exhaustive review of published articles to look for general recommendations.
      RESULTS: Randomized controlled trials, systemic reviews and meta-analysis are
      lacking in literature and there is wide variety of prescription techniques
      successfully used across the radiotherapy centers. BT can be delivered as
      superficial application (also called contact BT or plesiotherapy) or as
      interstitial for tumours thicker than 5 mm within any surface, including very
      irregular. In selected cases, particularly in tumours located within curved
      surfaces, BT can be advantageous modality from dosimetric and planning point of
      view when compared to external beam radiotherapy. The general rule in skin BT is
      that the smaller the target volume, the highest dose per fraction and the
      shortest overall length of treatment can be used. CONCLUSION: Skin cancer
      incidence is rising worldwide. BT offers an effective non-invasive or minimally
      invasive and relative short treatment that particularly appeals to elder and
      frail population.

PMID- 29455925
TI  - Differentiation of remitting neuromyelitis optica spectrum disorders from
      multiple sclerosis by integrating parameters from serum proteins and lymphocyte
      subsets.
AB  - Differential diagnosis for neuromyelitis optica spectrum disorder (NMOSD) and
      multiple sclerosis (MS) is always doubtful. To differentiate these diseases, we
      studied the immune status in the blood of patients with MS (n = 45) or NMOSD (n =
      23) at remission phase. Remitting NMOSD patients had increased levels of CXCL13
      and memory B cells, while remitting MS patients had elevated levels of galectin-9
      and Th1 cells. A diagnostic model with these four variables is built to
      distinguish remitting NMOSD from MS with a sensitivity of 91.30%. Our diagnostic
      model may help to improve the differentiation of remitting NMOSD from MS.

PMID- 29455926
TI  - Unravelling salutogenic mechanisms in the workplace: the role of learning.
AB  - OBJECTIVE: To explore the moderating and mediating role(s) of learning within the
      relationship between sense of coherence (SOC) and generalized resistance
      resources. METHOD: Cross-sectional study (N=481), using a self-administered
      questionnaire, of employees working in the healthcare sector in the Netherlands
      in 2017. Four residential healthcare settings and one healthcare-related Facebook
      group were involved. Multiple linear regression models were used to test for
      moderating and mediating effects of learning. RESULTS: Social relations, task
      significance, and job control significantly explained variance in SOC.
      Conceptual, social, and instrumental learning, combined, moderated the
      relationship between SOC and task significance. Instrumental learning moderated
      the relationship between job control and SOC. Social learning also mediated this
      relationship. Conceptual learning did not show any moderating or mediating
      effect. CONCLUSIONS: The relationship between SOC and the three GRRs seems to be
      strengthened or explained-to a certain extent-by instrumental and social
      learning. Healthcare organizations are recommended to promote learning through
      formal activities as well as through cooperation, feedback, sharing experiences,
      and job challenges. This requires employee participation and a multilevel
      interdisciplinary approach.

PMID- 29455927
TI  - Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast
      Cancer.
AB  - Carcinoma-associated fibroblasts (CAF) are key players in the tumor
      microenvironment. Here, we characterize four CAF subsets in breast cancer with
      distinct properties and levels of activation. Two myofibroblastic subsets (CAF
      S1, CAF-S4) accumulate differentially in triple-negative breast cancers (TNBC).
      CAF-S1 fibroblasts promote an immunosuppressive environment through a multi-step
      mechanism. By secreting CXCL12, CAF-S1 attracts CD4+CD25+ T lymphocytes and
      retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte
      survival and promotes their differentiation into CD25HighFOXP3High, through B7H3,
      CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T
      cell capacity to inhibit T effector proliferation. These data are consistent with
      FOXP3+ T lymphocyte accumulation in CAF-S1-enriched TNBC and show how a CAF
      subset contributes to immunosuppression.

PMID- 29455929
TI  - Haemophagocytic lymphohistiocytosis secondary to Epstein-Barr virus infection
      with fatal outcome.

PMID- 29455928
TI  - Transcriptional Regulation of the Warburg Effect in Cancer by SIX1.
AB  - Aerobic glycolysis (the Warburg effect) facilitates tumor growth, and drugs
      targeting aerobic glycolysis are being developed. However, how the Warburg effect
      is directly regulated is largely unknown. Here we show that transcription factor
      SIX1 directly increases the expression of many glycolytic genes, promoting the
      Warburg effect and tumor growth in vitro and in vivo. SIX1 regulates glycolysis
      through HBO1 and AIB1 histone acetyltransferases. Cancer-related SIX1 mutation
      increases its ability to promote aerobic glycolysis and tumor growth. SIX1
      glycolytic function is directly repressed by microRNA-548a-3p, which is
      downregulated, inversely correlates with SIX1, and is a good predictor of
      prognosis in breast cancer patients. Thus, the microRNA-548a-3p/SIX1 axis
      strongly links aerobic glycolysis to carcinogenesis and may become a promising
      cancer therapeutic target.

PMID- 29455930
TI  - Swelling in the malar region in a neonate.

PMID- 29455931
TI  - Massive haemolysis due to sepsis caused by Clostridium perfringens secondary to
      liver abscess. Presentation of two cases with a similar history.

PMID- 29455932
TI  - A paradigm shift on beta-thalassaemia treatment: How will we manage this old
      disease with new therapies?
AB  - Beta-thalassaemia causes defective haemoglobin synthesis leading to ineffective
      erythropoiesis, chronic haemolytic anaemia, and subsequent clinical
      complications. Blood transfusion and iron chelation allow long-term disease
      control, and haematopoietic stem cell transplantation offers a potential cure for
      some patients. Nonetheless, there are still many challenges in the management of
      beta-thalassaemia. The main treatment option for most patients is supportive
      care; furthermore, the long-term efficacy and safety of current therapeutic
      strategies are limited and adherence is suboptimal. An increasing understanding
      of the underlying molecular and cellular disease mechanisms plus an awareness of
      limitations of current management strategies are driving research into novel
      therapeutic options. Here we provide an overview of the current pathophysiology,
      clinical manifestations, and global burden of beta-thalassaemia. We reflect on
      what has been achieved to date, describe the challenges associated with currently
      available therapy, and discuss how these issues might be addressed by novel
      therapeutic approaches in development.

PMID- 29455933
TI  - The American Association of Heart Failure Nurses (AAHFN) certification review
      course: the impact on heart failure nurses' knowledge.

PMID- 29455934
TI  - Corrigendum to "Low molar excess of 4-oxo-2-nonenal and 4-hydroxy-2-nonenal
      promote oligomerization of alpha-synuclein through different pathways" [Free Rad.
      Biol. Med. (2017) 421-431].

PMID- 29455935
TI  - Engineering PGPMOs through Gene Editing and Systems Biology: A Solution for
      Phytoremediation?
AB  - In light of extensive urbanization and deforestation, toxic wastes are being
      released into the atmosphere, causing increased air and soil pollution.
      Conventional methods of soil remediation are time consuming and labor and cost
      intensive, rendering them uneconomical to maintain sustainable agriculture. One
      solution is to use natural resources like plants and microbes for
      phytoremediation. A thorough systemic knowledge of plant-microbe interactions
      will allow the use of gene editing and gene manipulation techniques to increase
      the efficiency of plants in phytoremediation. This Opinion article focuses on
      gene editing techniques used in plants and microbes for phytoremediation and also
      emphasizes their effectiveness, advancement, and future implications for
      sustainable and environmentally friendly agriculture.

PMID- 29455936
TI  - Engineering a Clinically Translatable Bioartificial Pancreas to Treat Type I
      Diabetes.
AB  - Encapsulating, or immunoisolating, insulin-secreting cells within implantable,
      semipermeable membranes is an emerging treatment for type 1 diabetes. This
      approach can eliminate the need for immunosuppressive drug treatments to prevent
      transplant rejection and overcome the shortage of donor tissues by utilizing
      cells derived from allogeneic or xenogeneic sources. Encapsulation device designs
      are being optimized alongside the development of clinically viable,
      replenishable, insulin-producing stem cells, for the first time creating the
      possibility of widespread therapeutic use of this technology. Here, we highlight
      the status of the most advanced and widely explored implementations of cell
      encapsulation with an eye toward translating the potential of this technological
      approach to medical reality.

PMID- 29455937
TI  - The Impact of Patient and Surgical Factors on the Rate of Postoperative Infection
      After Total Hip Arthroplasty-A New Zealand Joint Registry Study.
AB  - BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication
      after total hip arthroplasty (THA). The potential to define and modify risk
      factors for infection represents an important opportunity to reduce the incidence
      of PJI. This study uses New Zealand Joint Registry data to identify independent
      risk factors associated with PJI after primary THA. METHODS: Data on 91,585 THAs
      performed between 2000 and 2014 were analyzed. Factors associated with revision
      for PJI within 12 months were identified using univariate and multivariate
      analyses. RESULTS: Revision rates for PJI were 0.15% and 0.21% at 6 and 12
      months, respectively. Multivariate analysis showed significant associations with
      the American Society of Anesthesiologists grade (odds ratio [OR] 6.13, 95%
      confidence interval [CI] 1.28-29.39), severe or morbid obesity (OR 2.15, CI 1.01
      4.60 and OR 3.73, CI 1.49-9.39), laminar flow ventilation (OR 1.98, CI 1.38
      2.85), consultant-supervised trainee operations (OR 1.94, CI 1.22-3.08), male
      gender (OR 1.68, CI 1.23-2.30) and anterolateral approach (OR 1.62, CI 1.11
      2.37). Procedures performed in the private sector were protective for revision
      for infection (OR 0.68, CI 0.48-0.96). CONCLUSIONS: The PJI risk profile for
      patients undergoing THA is constituted of a complex of patient and surgical
      factors. Several patient factors had strong independent associations with
      revision rates for PJI. Although surgical factors were less important, these may
      be more readily modifiable in practice.

PMID- 29455938
TI  - Comparison of Periarticular Local Infiltration Analgesia With Femoral Nerve Block
      for Total Knee Arthroplasty: a Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Total knee arthroplasty (TKA) is accompanied by moderate-to-severe
      postoperative pain. Postoperative pain will hamper functional recovery and lower
      patients' satisfaction with surgery. Recently, periarticular local infiltration
      analgesia (LIA) has been widely used in TKA. However, there is no definite answer
      as to the efficacy and safety of LIA compared with femoral nerve block (FNB).
      METHOD: Randomized controlled trials about relevant studies were searched from
      PubMed (1996 to July 2017), Embase (1980 to July 2017), and Cochrane Library
      (CENTRAL, July 2017). Ten studies which compared LIA with FNB methods were
      included in our meta-analysis. RESULTS: Ten studies containing 950 patients met
      the inclusion criteria. Our pooled data indicated that LIA was as effective as
      the FNB in terms of visual analog scale score for pain at 24 hours (P = .52), 48
      hours (P = .36), and 72 hours (P = .27), and total morphine consumption (P =
      .27), range of motion (P = .45), knee society score (P = .51), complications (P =
      .81), and length of hospital stay (P = .75). CONCLUSIONS: Our current meta
      analysis results demonstrated that there were no differences in efficacy between
      the FNB and LIA method.

PMID- 29455940
TI  - Response to Letter Regarding Article "Prognostic value of CT-derived left atrial
      and left ventricular measures in patients with acute chest pain".

PMID- 29455939
TI  - Strategies to facilitate shared decision-making about pediatric oncology clinical
      trial enrollment: A systematic review.
AB  - OBJECTIVE: We conducted a systematic review to identify the strategies that have
      been recommended in the literature to facilitate shared decision-making regarding
      enrolment in pediatric oncology clinical trials. METHODS: We searched seven
      databases for peer-reviewed literature, published 1990-2017. Of 924 articles
      identified, 17 studies were eligible for the review. We assessed study quality
      using the 'Mixed-Methods Appraisal Tool'. We coded the results and discussions of
      papers line-by-line using nVivo software. We categorized strategies thematically.
      RESULTS: Five main themes emerged: 1) decision-making as a process, 2)
      individuality of the process; 3) information provision, 4) the role of
      communication, or 5) decision and psychosocial support. Families should have
      adequate time to make a decision. HCPs should elicit parents' and patients'
      preferences for level of information and decision involvement. Information should
      be clear and provided in multiple modalities. Articles also recommended providing
      training for healthcare professionals and access to psychosocial support for
      families. CONCLUSION: High quality, individually-tailored information, open
      communication and psychosocial support appear vital in supporting decision-making
      regarding enrollment in clinical trials. These data will usefully inform future
      decision-making interventions/tools to support families making clinical trial
      decisions. PRACTICE IMPLICATIONS: A solid evidence-base for effective strategies
      which facilitate shared decision-making is needed.

PMID- 29455941
TI  - ?

PMID- 29455943
TI  - ?

PMID- 29455942
TI  - ?

PMID- 29455944
TI  - ?

PMID- 29455945
TI  - Orbitofrontal damage reduces auditory sensory response in humans.

PMID- 29455946
TI  - Abstract semantics in the motor system? - An event-related fMRI study on passive
      reading of semantic word categories carrying abstract emotional and mental
      meaning.
AB  - Previous research showed that modality-preferential sensorimotor areas are
      relevant for processing concrete words used to speak about actions. However,
      whether modality-preferential areas also play a role for abstract words is still
      under debate. Whereas recent functional magnetic resonance imaging (fMRI) studies
      suggest an involvement of motor cortex in processing the meaning of abstract
      emotion words as, for example, 'love', other non-emotional abstract words, in
      particular 'mental words', such as 'thought' or 'logic', are believed to engage
      'amodal' semantic systems only. In the present event-related fMRI experiment,
      subjects passively read abstract emotional and mental nouns along with concrete
      action related words. Contrary to expectation, the results indicate a specific
      involvement of face motor areas in the processing of mental nouns, resembling
      that seen for face related action words. This result was confirmed when subject
      specific regions of interest (ROIs) defined by motor localizers were used. We
      conclude that a role of motor systems in semantic processing is not restricted to
      concrete words but extends to at least some abstract mental symbols previously
      thought to be entirely 'disembodied' and divorced from semantically related
      sensorimotor processing. Implications for neurocognitive theories of semantics
      and clinical applications will be highlighted, paying specific attention to the
      role of brain activations as indexes of cognitive processes and their
      relationships to 'causal' studies addressing lesion and transcranial magnetic
      stimulation (TMS) effects. Possible implications for clinical practice, in
      particular speech language therapy, are discussed in closing.

PMID- 29455947
TI  - The neural exploitation hypothesis and its implications for an embodied approach
      to language and cognition: Insights from the study of action verbs processing and
      motor disorders in Parkinson's disease.
AB  - As it is widely known, Parkinson's disease is clinically characterized by motor
      disorders such as the loss of voluntary movement control, including resting
      tremor, postural instability, and bradykinesia (Bocanegra et al., 2015; Helmich,
      Hallett, Deuschl, Toni, & Bloem, 2012; Liu et al., 2006; Rosin, Topka, &
      Dichgans, 1997). In the last years, many empirical studies (e.g., Bocanegra et
      al., 2015; Spadacenta et al., 2012) have also shown that the processing of action
      verbs is selectively impaired in patients affected by this neurodegenerative
      disorder. In the light of these findings, it has been suggested that Parkinson
      disorder can be interpreted within an embodied cognition framework (e.g.,
      Bocanegra et al., 2015). The central tenet of any embodied approach to language
      and cognition is that high order cognitive functions are grounded in the sensory
      motor system. With regard to this point, Gallese (2008) proposed the neural
      exploitation hypothesis to account for, at the phylogenetic level, how key
      aspects of human language are underpinned by brain mechanisms originally evolved
      for sensory-motor integration. Glenberg and Gallese (2012) also applied the
      neural exploitation hypothesis to the ontogenetic level. On the basis of these
      premises, they developed a theory of language acquisition according to which,
      sensory-motor mechanisms provide a neurofunctional architecture for the
      acquisition of language, while retaining their original functions as well. The
      neural exploitation hypothesis is here applied to interpret the profile of
      patients affected by Parkinson's disease. It is suggested that action semantic
      impairments directly tap onto motor disorders. Finally, a discussion of what
      theory of language is needed to account for the interactions between language and
      movement disorders is presented.

PMID- 29455948
TI  - Belief, delusion, hypnosis, and the right dorsolateral prefrontal cortex: A
      transcranial magnetic stimulation study.
AB  - According to the Two-Factor theory of delusional belief (see e.g. Coltheart at
      al., 2011), there exists a cognitive system dedicated to the generation,
      evaluation, and acceptance or rejection of beliefs. Studies of the
      neuropsychology of delusion provide evidence that this system is neurally
      realized in right dorsolateral prefrontal cortex (rDLPFC). Furthermore, we have
      shown that convincing analogues of many specific delusional beliefs can be
      created in nonclinical subjects by hypnotic suggestion and we think of hypnosis
      as having the effect of temporarily interfering with the operation of the belief
      system, which allows acceptance of the delusional suggestions. If the belief
      system does depend on rDLPFC, then disrupting the activity of that region of the
      brain by the application of repetitive transcranial magnetic stimulation (rTMS)
      will increase hypnotizability. Dienes and Hutton (2013) have reported such an
      experiment except that it was left DLPFC to which rTMS was applied. An effect on
      a subjective measure of hypnotizability was observed, but whether there was an
      effect on an objective measure could not be determined. We report two
      experiments. The first was an exact replication of the Dienes and Hutton
      experiment; here we found no effect of rTMS to lDLPFC on any hypnotic measure.
      Our second experiment used rTMS applied to right rather then left DLPFC. This
      right-sided stimulation enhanced hypnotizability (when hypnotic response was
      measured objectively), as predicted by our hypothesis. These results imply a role
      for rDLPFC in the cognitive process of belief evaluation, as is proposed in our
      two-factor theory of delusion. They are also consistent with a conception of the
      acceptance of a hypnotic suggestion as involving suspension of disbelief.

PMID- 29455949
TI  - Coxsackievirus B3-Induced Myocarditis: New Insights Into a Female Advantage.

PMID- 29455950
TI  - Sex Differences in Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is a chronic progressive disease characterized by
      exacerbations and remissions. It remains the most common sustained arrhythmia
      seen in clinical practice, and represents a major burden to health care systems.
      Similar to other cardiovascular conditions, significant sex-specific differences
      have been observed in the epidemiology (lower rate of prevalence in women, women
      present at a later age), pathophysiology (sex-related differences in AF triggers
      and substrate), clinical presentation (women are more likely symptomatic, with
      relatively more severe symptoms), and natural history. Moreover, similar to other
      cardiovascular conditions there are substantial sex-specific differences in the
      management of AF, with women being significantly less likely to receive
      therapeutic anticoagulation, attempts at rhythm control, or undergo invasive
      cardiovascular procedures. The purpose of this review is to explore these sex
      specific differences.

PMID- 29455952
TI  - Among Patients With Intracerebral Hemorrhage, Is Intensive Blood Pressure
      Decreasing Associated With Improved Outcome?

PMID- 29455951
TI  - Sex Hormone Contributes to Sexually Dimorphic Susceptibility in CVB3-Induced
      Viral Myocarditis via Modulating IFN-gamma+ NK Cell Production.
AB  - BACKGROUND: Viral myocarditis is a widespread cardiac disease associated with
      inflammation and myocardial injury and is predominantly caused by coxsackievirus
      B3 (CVB3) infection in humans as well as in mice. CVB3-induced myocarditis shows
      sexually dimorphic sensitivity and is more prevalent in male mice. Our previous
      studies showed that natural killer (NK) cells played an indispensable role in
      CVB3-induced myocarditis, and female mice exhibited less pathological cardiac
      interferon gamma (IFN-gamma)+ NK cell infiltration than did male mice. However,
      the precise mechanisms were not well elucidated. METHODS: We investigated the
      influence of estrogen on cardiac IFN-gamma+ NK cell enrichment in CVB3-induced
      myocarditis and explored the underlying molecular mechanism. RESULTS: In this
      study, we found that CVB3 stimulation could clearly induce IFN-gamma expression
      by NK cells; however, this trend could be blunted by estrogen treatment.
      Consistently, ovariectomized female mice with decreased estrogen levels exhibited
      substantially increased enrichment of cardiac IFN-gamma+ NK cells and displayed
      significantly aggravated myocarditis. Similarly, estrogen-treated male mice
      showed less cardiac IFN-gamma+ NK cell infiltration, accompanied by significantly
      alleviated viral myocarditis. In sharp contrast, sexually immature female and
      male mice (with similar estrogen levels) showed comparable levels of cardiac IFN
      gamma+ NK cell infiltration and similar levels of myocarditis severity. Upon
      further exploration of the underlying mechanisms, we found that estrogen could
      downregulate expression of Th1-specific T box transcription factor (T-bet), the
      key transcription factor associated with IFN-gamma production, in CVB3-stimulated
      NK cells. CONCLUSIONS: Overall, this study might help us understand the mechanism
      of increased cardiac infiltration by IFN-gamma+ NK cells in CVB3-infected male
      mice compared with that in female mice and might provide new clues for the sex
      bias in CVB3-induced myocarditis.

PMID- 29455953
TI  - The comprehensive characterization of adrenocortical steroidogenesis using two
      dimensional ultra-performance liquid chromatography - electrospray ionization
      tandem mass spectrometry.
AB  - The perturbation of the homeostasis of adrenocortical steroids plays a
      fundamental role in several pathological conditions. Currently, only a few of the
      substances involved in steroidogenesis are routinely analysed in clinical
      laboratories for the diagnosis of these conditions. Recently, interest has grown
      over the development of clinical assays of endogenous steroids using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). However, no approaches have
      assessed the adrenocortical steroidogenesis comprehensively. Here, a novel LC
      MS/MS assay is presented for evaluating the serum levels of all respective major
      substances (aldosterone, androstenedione, dehydroepiandrosterone,
      dehydroepiandrosterone sulfate, 11-deoxycorticosterone, 11-deoxycortisol, 21
      deoxycortisol, dihydrotestosterone, 17alpha-hydroxypregnenolone, 17alpha
      hydroxyprogesterone, corticosterone, cortisol, cortisone, pregnenolone,
      progesterone and testosterone). The analysis time was 5.5 min following highly
      efficient solid phase extraction conducted on a novel polymer phase with N
      polyvinylpyrrolidine branches. The method was validated in accordance with the
      respective guideline of the European Medicines Agency. The cross-validation of 8
      analytes with immunoassays was also accomplished. Two-dimensional chromatography
      allowed the elution of the 16 analytes between 2.3-4.6 min and with a sufficient
      resolution of isobaric compounds. Quantitation was performed throughout the
      clinically relevant concentration ranges. Within-run accuracy was 87.1-115%, 90.0
      109%, 87.2-111% and 87.6-107% at spiking levels 1 thru 4, while the precision was
      4.7-27.9%, 2.9-17.7%, 5.6-13.9% and 1.9-15.0%, respectively. Between-run accuracy
      was 81.0-119.5, 85.2-113, 87.4-113 and 93.1-113%, respectively, while the
      precision was 3.4-13.5%, 2.0-10.2%, 2.1-15.0%, and 1.5-6.6%, respectively. In
      cross-validation studies, the mean percentage differences ranged between -51.4%
      (dehydroepiandrosterone sulfate) and 17.5% (dehydroepiandrosterone). The approach
      allows the comprehensive characterization of the adrenocortical steroid
      homeostasis in clinical diagnostics.

PMID- 29455955
TI  - To med(iastinoscopy) or not to med(iastinoscopy).

PMID- 29455956
TI  - Extracorporeal membrane oxygenation in lung transplantation: No longer a four
      letter word.

PMID- 29455954
TI  - The Peroxisome Proliferator-Activated Receptor alpha is dispensable for cold
      induced adipose tissue browning in mice.
AB  - OBJECTIVE: Chronic cold exposure causes white adipose tissue (WAT) to adopt
      features of brown adipose tissue (BAT), a process known as browning. Previous
      studies have hinted at a possible role for the transcription factor Peroxisome
      Proliferator-Activated Receptor alpha (PPARalpha) in cold-induced browning. Here
      we aimed to investigate the importance of PPARalpha in driving transcriptional
      changes during cold-induced browning in mice. METHODS: Male wildtype and
      PPARalpha-/- mice were housed at thermoneutrality (28  degrees C) or cold (5 
      degrees C) for 10 days. Whole genome expression analysis was performed on
      inguinal WAT. In addition, other analyses were carried out. Whole genome
      expression data of livers of wildtype and PPARalpha-/- mice fasted for 24 h
      served as positive control for PPARalpha-dependent gene regulation. RESULTS: Cold
      exposure increased food intake and decreased weight of BAT and WAT to a similar
      extent in wildtype and PPARalpha-/- mice. Except for plasma non-esterified fatty
      acids, none of the cold-induced changes in plasma metabolites were dependent on
      PPARalpha genotype. Histological analysis of inguinal WAT showed clear browning
      upon cold exposure but did not reveal any morphological differences between
      wildtype and PPARalpha-/- mice. Transcriptomics analysis of inguinal WAT showed a
      marked effect of cold on overall gene expression, as revealed by principle
      component analysis and hierarchical clustering. However, wildtype and PPARalpha-/
      mice clustered together, even after cold exposure, indicating a similar overall
      gene expression profile in the two genotypes. Pathway analysis revealed that cold
      upregulated pathways involved in energy usage, oxidative phosphorylation, and
      fatty acid beta-oxidation to a similar extent in wildtype and PPARalpha-/- mice.
      Furthermore, cold-mediated induction of genes related to thermogenesis such as
      Ucp1, Elovl3, Cox7a1, Cox8, and Cidea, as well as many PPAR target genes, was
      similar in wildtype and PPARalpha-/- mice. Finally, pharmacological PPARalpha
      activation had a minimal effect on expression of cold-induced genes in murine
      WAT. CONCLUSION: Cold-induced changes in gene expression in inguinal WAT are
      unaltered in mice lacking PPARalpha, indicating that PPARalpha is dispensable for
      cold-induced browning.

PMID- 29455957
TI  - The elusive and ungrateful lymphatic circulation may be a key determinant of
      Fontan failure.

PMID- 29455958
TI  - Esophagectomy versus endoscopic resection for patients with early-stage
      esophageal adenocarcinoma: A National Cancer Database propensity-matched study.
AB  - OBJECTIVES: Endoscopic resection has been rapidly adopted in the treatment of
      early-stage esophageal tumors. We compared the outcomes after esophagectomy or
      endoscopic resection for stage T1a adenocarcinoma. METHODS: We queried the
      National Cancer Database for patients with T1a esophageal adenocarcinoma who
      underwent esophagectomy or endoscopic resection and generated a balanced cohort
      with 735 matched pairs using propensity-score matching. We then performed a
      multivariable Cox regression analysis on the matched and unmatched cohorts.
      RESULTS: We identified 2173 patients; 1317 (60.6%) underwent esophagectomy, and
      856 (39.4%) underwent endoscopic resection. In the unmatched cohort, patients who
      underwent esophagectomy were younger, more often not treated in academic
      settings, and more likely to have comorbidities (30.4% vs 22.5%, P = .002). They
      had longer hospital stays and more readmissions than patients who underwent
      endoscopic resection. Factors positively affecting overall survival were younger
      age, resection at an academic medical center, and lower Charlson-Deyo comorbidity
      score. In the matched cohort, patients who underwent esophagectomy had longer
      hospital stays and were more likely to be readmitted within 30 days (7.0% vs
      0.6%, P < .001). When a time period-specific partition was applied, endoscopic
      resection had a lower death hazard 0 to 90 days after resection (hazard ratio,
      0.15; P = .003), but this was reversed for survival greater than 90 days (hazard
      ratio, 1.34; P = .02). CONCLUSIONS: In patients with early-stage esophageal
      adenocarcinoma, survival appears equivalent after endoscopic resection or
      esophagectomy, but endoscopic resection is associated with shorter hospital
      stays, fewer readmissions, and less 90-day mortality. In patients surviving more
      than 90 days, esophagectomy may provide better overall survival.

PMID- 29455959
TI  - Discussion.

PMID- 29455960
TI  - Electric shock therapy for lung cancer: Taking palliation to the next level.

PMID- 29455961
TI  - The case of a chase for the kinase.

PMID- 29455962
TI  - Needle localization of small pulmonary nodules: Lessons learned.
AB  - BACKGROUND: Lung nodules that are small and deep within lung parenchyma, and have
      semisolid characteristics are often challenging to localize with video-assisted
      thoracoscopic surgery (VATS). We describe our cumulative experience using needle
      localization of small nodules before surgical resection. We report procedural
      tips, operative results, and lessons learned over time. METHODS: A retrospective
      review of all needle localization cases between July 1, 2006, and December 30,
      2016, at a single institution was performed. A total of 253 patients who
      underwent needle localization of lung nodules ranging from 0.6 to 1.2 cm before
      operation were enrolled. Nodules were localized by placing two 20-gauge Hawkins
      III coaxial needles from different trajectories with tips adjacent to the nodule,
      injection of 0.3 to 0.6 mL of methylene blue, and deployment of 2 hookwires,
      under computed tomography guidance. Patients then underwent VATS wedge resection
      for diagnosis, followed by anatomic resection for lung carcinoma. Procedural and
      perioperative outcomes were assessed. RESULTS: Needle localization was successful
      in 245 patients (96.8%). Failures included both wires falling out of lung
      parenchyma before operation (5 patients), wire migration (2 patients), and
      bleeding resulting in hematoma requiring transfusion (1 patient). The most common
      complication of needle localization was asymptomatic pneumothorax (11/253 total
      patients; 4.3%) and was higher in patients with bullous emphysema (9/35 patients;
      25.7%). Of the 8 individuals who had unsuccessful needle localization, 7 had
      successful wedge resection in the area of methylene blue injection that included
      the nodule; 1 required segmentectomy for diagnosis. Completion lobectomy (154
      VATS, 2 minithoracotomies) or VATS segmentectomy (18 patients) was performed in
      174 individuals with a diagnosis of non-small cell carcinoma or carcinoid. The
      average length of hospital stay was 1.4 days for wedge resection, 1.9 days for
      VATS segmentectomy, 3.1 days for VATS lobectomy, and 4.9 days for
      minithoracotomy. Perioperative survival was 100%. CONCLUSIONS: Needle
      localization with hookwire deployment and methylene blue injection is a safe and
      feasible strategy to localize small, deep lung nodules for wedge resection and
      diagnosis. Multidisciplinary coordination between the thoracic surgeon and the
      interventional radiologist is key to the success of this procedure.

PMID- 29455963
TI  - Discussion.

PMID- 29455964
TI  - Polytetrafluoroethylene conduits versus homografts for right ventricular outflow
      tract reconstruction in infants and young children: An institutional experience.
AB  - OBJECTIVE: Our institution uses a valved polytetrafluoroethylene conduit as an
      alternative to homografts. The objective of this study was to investigate the
      performance of bicuspid valved polytetrafluoroethylene conduits used for right
      ventricular outflow tract reconstruction in children aged less than 2 years and
      to evaluate risk factors for earlier conduit explant. METHODS: We performed an
      Institutional Review Board-approved retrospective chart review of all patients
      aged less than 2 years who underwent surgical right ventricular outflow tract
      reconstruction with a bicuspid valved polytetrafluoroethylene conduit or
      homograft conduit from July 2004 to December 2014. The end points of the study
      were defined as conduit explant, conduit explant or reintervention, conduit
      stenosis, and conduit insufficiency. RESULTS: Fifty-four patients underwent 65
      right ventricular outflow tract reconstructions with a bicuspid valved
      polytetrafluoroethylene conduit (n = 39) or a homograft conduit (n = 26, 23
      pulmonary, 3 aortic). The majority of diagnoses were truncus arteriosus (n = 28)
      and tetralogy of Fallot with pulmonary atresia (n = 19). Median age of patients
      at surgery was 134 (8-323) days and 128 (7-384) days in the PTFE and homograft
      groups, respectively. There was no difference in demographic data between the 2
      groups. Time-to-event analysis demonstrated no difference in time to explant (P =
      .474) or time to explant or reintervention (P = .206) between the 2 conduit
      types. Younger age at surgery was the only independent risk factor for conduit
      explant (subdistribution hazard ratio 1.104 per 30 days younger, P < .001). There
      was no significant influence of conduit type on the development of moderate
      conduit stenosis (P = .931) or severe conduit insufficiency (P = .880). Larger
      conduit z score was protective for the development of moderate conduit stenosis
      (subdistribution hazard ratio, 0.46; P = .001). CONCLUSIONS: Bicuspid valved
      polytetrafluoroethylene conduits are a satisfactory choice for right ventricular
      outflow tract reconstruction in patients aged less than 2 years. Their
      availability, low cost, and lack of potential sensitization make them an
      appealing alternative to homograft conduits.

PMID- 29455965
TI  - What the nose knows: Trends in biomimetic sensor technology.

PMID- 29455966
TI  - Fabrication of chitosan gel droplets via crosslinking of inverse Pickering
      emulsifications.
AB  - Hydrophobic and dispersible functionalized reduced graphene oxide (FrGO) was
      employed to prepare chitosan gel droplets by crosslinking an inverse Pickering
      emulsion. The emulsion was prepared using toluene as the continuous phase and a
      chitosan aqueous solution as the dispersed phase. The effects of the FrGO
      concentration and the water/oil ratio on the chitosan droplet morphology were
      studied. At appropriate concentrations, the FrGO acted as a stabilizer and
      chitosan gel droplets were formed. Decreasing the FrGO concentration or
      increasing the water/oil ratio was unfavorable to the formation of chitosan
      droplets. Using this method, drug loaded chitosan gel droplets (microgels) were
      prepared and their release profiles as well as the factors that influence the
      drug release were investigated.

PMID- 29455967
TI  - Gastroprotective activity of polysaccharide from Hericium erinaceus against
      ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric
      ulcer, and its antioxidant activities.
AB  - The gastroprotective activity of Hericium erinaceus polysaccharide was
      investigated in rats. The antioxidant activities were also evaluated. Pre
      treatment of polysaccharide could reduce ethanol-induced gastric mucosal lesion
      and pylorus ligation-induced gastric ulcer. The polysaccharide exhibited
      scavenging activities of 1, 1-diphenyl-2-picryl-hydrozyl and hydroxyl radicals,
      and ferrous ion-chelating ability. In the pylorus ligation-induced model, gastric
      secretions (volume of gastric juice, gastric acid, pepsin and mucus) of ulcer
      rats administrated with polysaccharide were regulated. Levels of tumor necrosis
      factor-alpha and interleukins-1beta in serum, and myeloperoxidase activity of
      gastric tissue were reduced, while antioxidant status of gastric tissue was
      improved. Defensive factors (nitric oxide, prostaglandin E2, epidermal growth
      factor) in gastric tissue were increased. These results indicate that Hericium
      erinaceus polysaccharide possess gastroprotective activity, and the possible
      mechanisms are related to its regulations of gastric secretions, improvements of
      anti-inflammatory and antioxidant status, as well as increments of defensive
      factors releases.

PMID- 29455968
TI  - Nanostructured electrospun nonwovens of poly(epsilon-caprolactone)/quaternized
      chitosan for potential biomedical applications.
AB  - Blend solutions of poly(epsilon-caprolactone) (PCL) and N-(2-hydroxy)-propyl-3
      trimethylammonium chitosan chloride (QCh) were successfully electrospun. The
      weight ratio PCL/QCh ranged in the interval 95/5-70/30 while two QCh samples were
      used, namely QCh1 (DQ- = 47.3%; DPv- = 2218) and QCh2 (DQ- = 71.1%; DPv- = 1427).
      According to the characteristics of QCh derivative and to the QCh content on the
      resulting PCL/QCh nonwoven, the nanofibers displayed different average diameter
      (175 nm-415 nm), and the nonwovens exhibited variable porosity (57.0%-81.6%),
      swelling capacity (175%-425%) and water vapor transmission rate (1600 g m-2 24 h
      2500 g m-2 24 h). The surface hydrophilicity of nonwovens increases with
      increasing QCh content, favoring fibroblast (HDFn) adhesion and spreading.
      Tensile tests revealed that the nonwovens present a good balance between
      elasticity and strength under both dry and hydrated state. Results indicate that
      the PCL/QCh electrospun nonwovens are new nanofibers-based biomaterials
      potentially useful as wound dressings.

PMID- 29455969
TI  - Application of response surface methodology to tailor the surface chemistry of
      electrospun chitosan-poly(ethylene oxide) fibers.
AB  - Chitosan is a promising biocompatible polymer for regenerative engineering
      applications, but its processing remains challenging due to limited solubility
      and rigid crystalline structure. This work represents the development of
      electrospun chitosan/poly(ethylene oxide) blend nanofibrous membranes by means of
      a numerical analysis in order to identify and tailor the main influencing
      parameters with respect to accessible surface nitrogen functionalities which are
      of importance for the biological activity as well as for further
      functionalization. Depending on the solution composition, both gradient fibers
      and homogenous blended fiber structures could be obtained with surface nitrogen
      concentrations varying between 0 and 6.4%. Response surface methodology (RSM)
      revealed chitosan/poly(ethylene oxide) ratio and chitosan molecular weight as the
      main influencing factors with respect to accessible nitrogen surface atoms and
      respective concentrations. The model showed good adequacy hence providing a tool
      to tailor the surface properties of chitosan/poly(ethylene oxide) blends by
      addressing the amount of accessible chitosan.

PMID- 29455970
TI  - Facile synthesis of palladium and gold nanoparticles by using dialdehyde
      nanocellulose as template and reducing agent.
AB  - Cellulose nanofibrils (CNFs) were firstly prepared by 2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPO) oxidation and further oxidized to 2,3
      dialdehyde nanocelluloses (DANCs) by periodate oxidation. Furthermore, by using
      DANCs as reducing as well as stabilizing agent, palladium (Pd) and gold (Au)
      nanoparticles (NPs) supported on nanocellulose (PdNPs@NC and AuNPs@NC) were
      synthesized, respectively. The reduction of Pd or Au ions to its metallic form by
      DANCs was confirmed by UV-vis spectra, XRD, and XPS. TEM results showed that Pd
      and Au NPs were homogenously deposited onto cellulose nanofibrils, respectively.
      The catalytic performance of PdNPs@NC was further investigated by Suzuki coupling
      reaction. The product yield of the Suzuki coupling reaction between aryl bromides
      and phenyl boronic acid was more than 90% after 1 h with 0.1 mol% PdNPs@NC
      catalyst, which demonstrated that the synthesized PdNPs@NC nanohybrid could be
      successfully applied in Suzuki coupling reaction with an efficient catalytic
      activity.

PMID- 29455971
TI  - Chitosan-based ion-imprinted cryo-composites with excellent selectivity for
      copper ions.
AB  - An original strategy is proposed here to design chitosan-based ion-imprinted cryo
      composites (II-CCs) with pre-organized recognition sites and tailored porous
      structure by combining ion-imprinting and ice-templating techniques. The cryo
      composites showed a tube-like porous morphology with interconnected parallel
      micro-channels, the distance between the channel walls being around 15 MUm. Both
      the entrapment of a natural zeolite and the presence of carboxylate groups,
      generated by partial hydrolysis of amide moieties, led to II-CCs with controlled
      swelling ratios (25-40 g/g, depending on pH) and enhanced overall chelating
      efficiency (260 mg Cu2+/g composite). To point out the importance of introducing
      Cu2+ recognition sites, sorption experiments using mixtures of Cu2+ and other
      competing ions (Co2+, Ni2+, Zn2+ or/and Pb2+) were also carried out. The higher
      values of selectivity coefficients obtained for the II-CCs compared to those of
      non-imprinted ones highlight the remarkable potential of our sorbents for
      decontamination of wastewaters and recycling of Cu2+ ions.

PMID- 29455972
TI  - Synthesis of carboxymethyl starch-g-polyvinylpyrolidones and their properties for
      the adsorption of Rhodamine 6G and ammonia.
AB  - Carboxymethyl starch-g-polyvinylpyrolidones (CMS-g-PVPs) were prepared by
      grafting of carboxymethyl starch (CMS) with N-vinylpyrolidone (NVP) using
      different initiators. The grafting percentage of all the modified starches was
      determined and the modified starch (CMS-g-PVP-5) with maximum grafting percentage
      was characterized by elemental analysis, 1H NMR and FT-IR spectroscopy.
      Crystallinity and thermal properties of CMS-g-PVP-5 were analysed by XRD and TGA,
      respectively. CMS-g-PVP-5 was then utilized for the adsorption of Rhodamine 6G
      (dye) from water under different pH, temperature, adsorbate doze and adsorbent
      concentration. This modified starch showed good adsorption ability towards
      Rhodamine 6G. CMS-g-PVP-5 was also applied for the adsorption of ammonia gas and
      proved an exciting adsorbent for ammonia.

PMID- 29455973
TI  - Microbicidal gentamicin-alginate hydrogels.
AB  - Sodium alginate (Alg) reacted with antibiotic gentamicin sulfate (GS) in an
      aqueous-phase condition mediated by carbodiimide chemistry, in the molar ratios
      Alg: GS of (1:0.5), (1:1) and (1:2). The Alg-GS conjugated derivatives were
      characterized by elemental analysis for nitrogen content, Fourier transform
      infrared spectroscopy in the attenuated total reflection mode (FTIR-ATR), X-ray
      photoelectron spectroscopy (XPS), scanning electron microscopy (SEM),
      thermogravimetric analyses (TGA) and water sorption measurements. XPS and FTIR
      ATR analyses clearly indicated that GS molecules covalently attached to the
      backbone of the alginate chains by amide bond formation. The highest amount of GS
      bound to Alg (43.5 +/- 0.4 wt%) and the highest swelling ratio (4962 +/- 661%)
      were observed for the Alg-GS (1:2) sample. Bioluminescence assays with
      Pseudomonas aeruginosa PAO1/lecA:lux and colony forming counting of
      Staphylococcus aureus and Escherichia coli upon contact with all Alg-GS
      conjugates revealed microbicidal activity; however, Alg-GS (1:2) was the most
      efficient, due to the highest GS content.

PMID- 29455974
TI  - Structural elucidation of a pectic polysaccharide from Fructus Mori and its
      bioactivity on intestinal bacteria strains.
AB  - Many studies suggested that polysaccharides could impact on the gut microbiota.
      To discover new polysaccharides which influence intestinal beneficial bacteria, a
      pectin polysaccharide FMP-6-S2 with an average molecular weight of 86.83 kDa was
      purified from Fructus Mori. The monosaccharide residue analysis indicated that
      FMP-6-S2 was composed of rhamnose, galacturonic acid, galactose and arabinose in
      a molar ratio of 30.86: 24.78: 28.70: 15.61. The backbone of FMP-6-S2 contained
      1, 4-linked alpha-GalpA and 1, 2-linked alpha-Rhap with branches substituted at C
      4 position of rhamnose. The branches were composed of 1, 4-linked beta-Galp,
      terminal (T) - and 1, 3, 6-linked beta-Galp, T- and 1, 5-linked alpha-Araf.
      Bioactivity test results suggested that FMP-6-S2 and its degraded product could
      promote growth of intestinal bacteria, B. thetaiotaomicron, which is a dominate
      strain in the gut of human to benefit intestinal mucosa. These results suggested
      that FMP-6-S2 and its degraded product might improve human wellness by modulating
      B. thetaiotaomicron.

PMID- 29455975
TI  - Revealing a novel natural bioflocculant resource from Ruditapes philippinarum:
      Effective polysaccharides and synergistic flocculation.
AB  - A novel natural bioflocculant resource of Ruditapes philippinarum conglutination
      mud (RPM) with the effective flocculation components was firstly reported in this
      study. Experimental results showed that the maximum flocculation activity (FR) of
      RPM to kolin clay reached 86.7% in deionized water assay system and 91.8% in sea
      water assay system. RPM could flocculate marine microalgae Chlorella salina with
      a FR of 74.1%. The crude RPM polysaccharides extract(RPMP) were composed of 97.8%
      (w/w) polysaccharides and 2.2% (w/w) protein and the functional components of
      pure RPMP were firstly discovered to be two complex heteropolysaccharides of RPMP
      1 and RPMP-2 with similar monosaccharides composition except glucose content. The
      molecular weights of RPMP-1 and RPMP-2 were 5.7 kDa and 18.0 kDa, respectively.
      It is interesting to find that RPMP-1 and RPMP-2 exhibited synergistic
      flocculation activity of 65.6% at a mass ratio of 2:1 as in crude RPMP,
      suggesting the original proportion is significant to synergistic flocculation.

PMID- 29455976
TI  - Near-infrared emissive lanthanide hybridized nanofibrillated cellulose nanopaper
      as ultraviolet filter.
AB  - The lanthanide complexes [Yb(fac)3(H2O)2, Yb(tta)3(H2O)2, Nd(tta)3(H2O)2]
      functionalized nanofibrillated cellulose (Ln-NFC) nanopapers with near-infrared
      (NIR) luminescence and high transparency are rapidly fabricated after solvent
      exchange using a simple suction filtration film-making method. The effects of NFC
      and lanthanide complexes content on their photophysical properties of Ln-NFC
      nanopapers and their mechanism of UV filters are fully investigated. With
      increasing lanthanide complexes content in the Ln-NFC nanopaper, their
      transmittances are gradually decreased while their NIR luminescences are
      obviously increased. Yb-fac NFC nanopaper has high UVB block rate at 298 nm,
      whereas the high UVA block ratio of Ln-tta NFC nanopaper is observed at 345 nm.
      Ln-NFC nanopapers show a much higher photostability without decomposition under
      UV irradiation at 365 nm over 5 h. The emission spectra of the Ln-NFC nanopaper
      process the NIR luminescence of the corresponding lanthanide ions through the
      efficient triplet-triplet energy transfer process. Ln-NFC nanopapers can bring a
      brilliant future for UV filters, labeling fields and marking soft materials
      application.

PMID- 29455977
TI  - Structural and physicochemical characterization of thermoplastic corn starch
      films containing microalgae.
AB  - This work provides an in-depth analysis on how the addition of different
      microalgae species (Nannochloropsis, Spirulina and Scenedesmus) affected the
      structural and physicochemical properties of thermoplastic corn starch
      biocomposites. Structural characterization was conducted by combined SAXS/WAXS
      experiments and it was correlated with mechanical and barrier properties of the
      biocomposites. A water vapour permeability drop of ca. 54% was observed upon
      addition of the different microalgae species. The oxygen permeability and the
      mechanical properties of biocomposites containing Spirulina or Scenedesmus were
      not improved since the presence of microalgae hindered the re-arrangement and
      packing of the lamellar structure of starch polymeric chains, according to the
      SAXS results. Nannochloropsis caused a great reduction of the matrix rigidity
      and, the oxygen permeability was also improved. Therefore, all of these features
      make the Nannochloropsis biocomposites an alternative to generate biodegradable
      food packaging materials with the additional advantage that they can be easily
      scaled-up.

PMID- 29455978
TI  - Chitosan adsorption on nanofibrillated cellulose with different aldehyde content
      and interaction with phosphate buffered saline.
AB  - The chitosan adsorption on films prepared using nanofibrillated cellulose (NFC)
      with different content of aldehyde group was studied by means of Quartz Crystal
      Microbalance with Dissipation (QCM-D). Results showed that frequency change
      (Deltaf) was higher when the chitosan adsorbed on NFC film consisting more
      aldehyde group indicating the higher adsorption. The (Deltaf) and dissipation
      (DeltaD) factors completely changed during adsorption of chitosan pre-treated
      with acetic acid: Deltaf increased and DeltaD decreased, oppositely to un-treated
      chitosan adsorption. After acid treatment, molecular weight and crystallinity
      index of chitosan decreased addition to change in chemical structure. It was
      found that more phosphate buffered saline (PBS), as a model liquid for wound
      exudate, adsorbed to acid treated chitosan-NFC film, especially to film having
      more aldehyde groups. Comparing with bare NFC film, chitosan-NFC films adsorbed
      less PBS because chitosan crosslinked the NFC network and blocked the functional
      groups of NFC and thus, preventing swelling film.

PMID- 29455979
TI  - Proton exchange membrane based on chitosan and solvent-free carbon nanotube
      fluids for fuel cells applications.
AB  - Poor dispersion and inert ionic conduction are two major obstacles towards using
      carbon nanotubes (CNTs) to modify polymer electrolyte membranes (PEMs) in energy
      conversion devices. In this work, solvent-free carbon nanotube fluids (CNT
      fluids) with liquid-like behavior are prepared through an ion exchange method and
      incorporated into a chitosan (CS) matrix to fabricate composite membranes. The
      electrostatic interactions between SO3- groups in the CNT fluids and NH2 groups
      in the CS matrix, in addition to the unique flow properties of the CNT fluids,
      promote the uniform dispersion of CNT fluids in the CS matrix. Markedly, the
      CS/CNT fluid-3 composite membrane is simultaneously reinforced and toughened by
      180% and 300% compared to pure CS membrane, respectively. Moreover, the SO3-
      groups in the CNT fluids facilitate the proton transfer such that the proton
      conductivity of CS/CNT fluid-3 composite membrane reaches a maximum value of
      0.044 S cm-1 at 80  degrees C.

PMID- 29455980
TI  - A one-step approach to make cellulose-based hydrogels of various transparency and
      swelling degrees.
AB  - This work reports a "one-step" approach to make cellulose-based hydrogels in
      NaOH/urea aqueous solution via mixing N,N'-methylene bisacrylamide (MBA) with
      cellulose solution at room temperature. The hydrogels were revealed to be formed
      by an addition reaction between the double bonds of MBA and the hydroxyl groups
      of cellulose. Two states of hydrogels, i.e. the freshly prepared hydrogels and
      the hydrogels at swelling equilibrium state in deionized water, were prepared.
      Water retention of the hydrogels can reach up to 330 g H2O/g dry hydrogel. The
      freshly prepared hydrogels showed increased mechanical strength and high
      transparency (94%) with the addition of MBA. The hydrogels at swelling
      equilibrium state displayed macroporous structures with the pore diameter up to
      0.65 mm and showed significantly varied properties with various amount of MBA.
      The obtained hydrogel could be used as a good blank template for the
      functionalization of cellulose-based hydrogel.

PMID- 29455981
TI  - Digestibility of fucosylated glycosaminoglycan from sea cucumber and its effects
      on digestive enzymes under simulated salivary and gastrointestinal conditions.
AB  - The digestibility of fucosylated glycosaminoglycan (FG) and its effects on
      digestive enzymes were investigated using an in vitro digestion model. Results
      showed that the molecular weight and the reducing sugar content of FG were not
      significantly changed, and no free monosaccharides released from FG were detected
      after the salivary, gastric and intestinal digestion, indicating that both the
      backbone and the sulfated fucose branches of FG are resistant to be cleaved in
      the saliva and gastrointestinal tract environments. Furthermore, FG can dose
      dependently inhibit digestive enzymes such as alpha-amylase, pepsin and
      pancreatic lipase in different degrees under the simulated digestion conditions
      due to the sulfate and carboxyl groups. These physiological effects of FG may
      help control the postprandial glucose concentration and have the potential in the
      prevention or treatment of reflux disease and obesity. The findings may provide
      information on the digestibility and beneficial physiological effects of FG as a
      potential natural product to promote human health.

PMID- 29455982
TI  - Investigation of OH bond energy for chemically treated alfa fibers.
AB  - This work aims to study the hydrogen bond energy and distance for different
      samples of alfa fibers treated with thymol. The treatment duration and thymol
      concentration were varied and seem to have a great influence on infrared band
      intensities and positions. The number of hydrogen bonds is related to the
      infrared band intensity, whereas their energy and distance depend on the infrared
      band position. It was proven that the free hydroxyl groups are weakened and tend
      to disappear with fiber treatment. It is the same for intermolecular hydrogen
      bands between cellulosic chains that present a decrease in both intensity and
      frequency. The two intramolecular hydrogen bands increase in intensity but
      exhibit different behaviors regarding the calculated energy: while the band at
      3268 cm-1 is weakened and shifted to higher wavenumbers, that at 3338 cm-1 keeps
      the same peak position and energy.

PMID- 29455983
TI  - Electrochemical writing on edible polysaccharide films for intelligent food
      packaging.
AB  - Polysaccharide films used as intelligent food packaging possess the advantages of
      renewability, safety and biodegradability. Printing on the polysaccharidic food
      packaging is challenging due to the high demand for edible-ink and the need for a
      suitable printing technique. In this work, we propose an electrochemical method
      for writing on polysaccharide film. Unlike conventional printing, this
      electrochemical writing process relies on the pH responsive color change of
      anthocyanin embedded in the chitosan/agarose hydrogel. By biasing a negative
      potential to a stainless wire (used as a pen) contacting the surface of the
      chitosan/agarose/ATH hydrogel, the locally generated pH change induced the color
      change of ATH and wrote programmed information on the hydrogel. We demonstrate
      the writing can be temporary in the hydrogel but stable when the hydrogel is
      dried. We further demonstrate that the written film is applicable for the
      detection of the spoilage of crucian fish. The reported electrochemical writing
      process provides a novel method for printing information on polysaccharide film
      and great potential for intelligent food packaging.

PMID- 29455985
TI  - Pd@HNTs-CDNS-g-C3N4: A novel heterogeneous catalyst for promoting ligand and
      copper-free Sonogashira and Heck coupling reactions, benefits from halloysite and
      cyclodextrin chemistry and g-C3N4 contribution to suppress Pd leaching.
AB  - For the first time, a ternary hybrid system composed of halloysite nanotubes,
      HNTs, cyclodextrin nanosponges, CDNS, and g-C3N4 is prepared and used for
      immobilization of Pd(0) nanoparticles and development of a heterogeneous
      catalyst, Pd@HNTs-CDNS-g-C3N4 for promoting ligand and copper-free Sonogashira
      and Heck coupling reactions in aqueous media. HNT as a porous tubular clay with
      outstanding thermal, mechanical and textural properties can act as a support for
      immobilizing Pd nanoparticles. The role of CDNS can be explained on the base of
      its capability to form inclusion complexe with substrates and bringing them in
      the vicinity of the catalytic active sites. Regarding the role of g-C3N4 in
      catalysis, it is proved that its presence can suppress the Pd leaching
      dramatically. The contribution of each component as well as synergistic effect
      between them results in high catalytic activity and recyclability (up to 10
      reaction runs) of the catalyst.

PMID- 29455984
TI  - Hyaluronate coating enhances the delivery and biocompatibility of gold
      nanoparticles.
AB  - For targeted delivery with nanoparticles (NPs) as drug carriers, it is imperative
      that the NPs are internalized into the targeted cell. Surface properties of NPs
      influence their interactions with cells. We examined the responses of retinal
      pigment epithelial cells, NIH 3T3 fibroblast cells, and Chinese hamster ovary
      cells to gold nanoparticles (Au NPs) in their nascent form as well as coated with
      end-thiolated hyaluronate (HS-HA). The grafting density of HS-HA on Au NPs was
      calculated based on total organic carbon measurements and thermal gravimetric
      analysis. We imaged the intracellular NPs by 3D confocal microscopy. We
      quantified viability and generation of reactive oxygen species (ROS) of the cells
      to Au NPs and monitored cell-surface attachment via electrical cell-substrate
      impedance sensing. The results confirmed that receptors on cell surfaces, for HA,
      are critical in internalizing HS-HA-Au NPs, and HA may mitigate ROS pathways
      known to lead to cell death. The 50- and 100-nm HS-HA-Au NPs were able to enter
      the cells; however, their nascent forms could not. This study shows that the
      delivery of larger Au NPs is enhanced with HS-HA coating and illustrates the
      potential of HA-coated NPs as a drug delivery agent for inflamed, proliferating,
      and cancer cells that express CD44 receptors.

PMID- 29455986
TI  - Simultaneous improvement of thermal stability and redispersibility of cellulose
      nanocrystals by using ionic liquids.
AB  - Cellulose nanocrystals (CNCs) are predominantly obtained by the traditional
      sulfuric acid hydrolysis process. However, as-prepared CNCs powder features low
      thermal stability and poor redispersibility due to the existence of sulfonate
      groups and the hydrogen bond interaction among particles. Herein, by mixing the
      ionic liquid [BMIm][BF4] with freshly prepared CNCs without dialysis through a
      simple rotary evaporate procedure, the simultaneous improvement of thermal
      stability and redispersibility of CNCs has been achieved. By combining FTIR, TGA
      and DLS measurements, the critical role of rotary evaporates process for
      improving the thermal stability of CNCs has been discussed. Furthermore, the
      poly(lactic acid) (PLLA)/IL-CNC nanocomposites with enhanced mechanical
      properties were prepared by the melt-mixing method. This study provides a green
      and simple strategy for preparing dried CNC powders, which has a great potential
      in large-scale production of fully bio-based nanocomposites.

PMID- 29455987
TI  - Design and biological response of doxycycline loaded chitosan microparticles for
      periodontal disease treatment.
AB  - The aim of this study was to develop chitosan (CS) microparticulated mucoadhesive
      drug delivery system (DDS) with improved therapeutic performance and biological
      responce. Ionotropic gelation/spray drying process was used for preparation of
      doxycycline hyclate (DOXY) loaded low and medium molecular weight (LMw and MMw)
      CS/sodium tripolyphosphate microparticles (CS/TPP MPs), further coated with ethyl
      cellulose (EC) using coacervation/solvent displacement technique. The relevant
      physico-chemical and biopharmaceutical properties were optimized using
      experimental design approach. Both coated and uncoated CS/TPP MPs showed high
      mucoadhesive potential and did not affect the viability of the tested epithelial
      cell line. The MPs induced slow and gradual apoptotic response in murine
      macrophage cell line RAW 264.7 and the observed effect depended upon formulation
      type and MP concentration. Biological effect of the CS-based MPs observed in our
      experiments point to synergism of the biological response of the carrier with the
      anti-inflammatory effect of DOXY.

PMID- 29455988
TI  - Fabrication of novel nanohybrids by impregnation of CuO nanoparticles into
      bacterial cellulose and chitosan nanofibers: Characterization, antimicrobial and
      release properties.
AB  - The efficiency of bacterial cellulose nanofibers (BCNF) and chitosan nanofibers
      (CHNF) were compared, aiming at fabricating novel organic-inorganic nanohybrids
      containing copper oxide (CuO) nanoparticles (NPs). FT-IR spectra confirmed the
      formation of real nanohybrids through occurring new interactions between CuO NPs
      and nanofibers. XRD results indicated that both the crystallite size and the
      crystallinity index of nanofibers decreased after nanohybrid formation.
      Noticeably, these morphological changes for CHNF were more than those for BCNF.
      Strong attachment of CuO-NPs to the BCNF and CHNF nanofibrils was observed in FE
      SEM images. After 72 h, CuO releasing for CuO-BCNF and CuO-CHNF nanohybrids was
      recorded as 65.5% and 47.7%, respectively. The antibacterial activity of CuO NPs
      against both Gram-positive and Gram-negative bacteria decreased after attachment
      to BCNF. However, a synergistic effect was observed between CuO and CHNF on the
      antimicrobial activity of CuO-CHNF nanohybrid. This study demonstrated the
      potential of fabricated nanohybrids in water purification and food packaging
      applications.

PMID- 29455989
TI  - Biocompatible nanocomposite of carboxymethyl cellulose and functionalized carbon
      norfloxacin intercalated layered double hydroxides.
AB  - In recent years, the development of systems with progressive drug release
      properties, which is an effective technique for the use of drugs, has aroused
      great interest in the field of controlled release formulations. In this work,
      hybrid materials containing citric acid cross-linked carboxymethyl cellulose
      (CMC) and norfloxacin (NOR) intercalated layered double hydroxide (LDH) deposited
      over the surface of functionalized carbon (AC) were prepared. The synthesized
      CMC@AC-LDHNOR nanohybrids were characterized using different techniques and in
      vitro NOR release behaviors were investigated in phosphate buffer saline, pH 7.4
      at 37  degrees C. On the basis of the release profiles, it was found that NOR
      release was delayed when it was intercalated in AC-LDH which in presence of
      modified CMC decreases further. The nanohybrids indicated enhancement of
      antibacterial activity against gram-negative and gram-positive bacteria. The MTT
      assay showed their non-toxic behavior against ovarian normal epithelial and
      cancer cells, suggesting their potential use as drug carriers.

PMID- 29455990
TI  - Enhancement of bio-stability and mechanical properties of hyaluronic acid
      hydrogels by tannic acid treatment.
AB  - Hyaluronic acid (HA) has been widely investigated because of its excellent
      biocompatibility and its ability to form hydrogels with various chemical
      modifications. However, HA hydrogels undergo rapid degradation and exhibit poor
      mechanical stability under physiological conditions. Tannic acid (TA), a
      naturally occurring polyphenol found in plants and fruits, has recently attracted
      interest as a crosslinking agent because of its abundant hydroxyl groups. In this
      study, we prepared HA hydrogels chemically crosslinked by polyethylene glycol
      diglycidyl ether (PEGDE) and treated with TA in an attempt to enhance the
      physical properties of HA hydrogels. TA acts as a physical crosslinker owing to
      the strong hydrogen bonding between TA and PEGDE, resulting in improved
      mechanical properties that support both cell attachment and proliferation without
      any sign of cytotoxicity. The enzymatic stability of the HA-TA hydrogels was
      significantly enhanced with the addition of TA, which was attributed to the
      hyaluronidase inhibition activity of TA. Additionally, the antioxidant potential
      of TA resulted in good resistance to degradation by reactive oxygen species,
      which can be generated in human tissues.

PMID- 29455991
TI  - Water-soluble chitosan derivatives and pH-responsive hydrogels by selective C-6
      oxidation mediated by TEMPO-laccase redox system.
AB  - Chitosan is a polysaccharide with recognized antioxidant, antimicrobial and wound
      healing activities. However, this polymer is soluble only in dilute acidic
      solutions, which restricts much of its applications. A usual strategy for
      improving the functionality of polysaccharides is the selective oxidation
      mediated by 2,2,6,6-tetra-methyl-1-piperidinidyloxy (TEMPO) using laccase as a co
      oxidant. In this work, the TEMPO-laccase redox system was used for the first time
      to selectively oxidize chitosan in order to produce tailored derivatives. The
      reaction was performed at pH 4.5 under continuous air supply and the oxidized
      products were characterized structurally and functionally. The TEMPO-laccase
      oxidation successfully added aldehyde and carboxylate groups to chitosan
      structure resulting in derivatives with oxidation between 4 and 7%. These
      derivatives showed increased solubility and decreased viscosity in solution. If
      chitosan is dissolved in diluted hydrochloric acid prior to TEMPO-laccase
      oxidation, a crosslinked chitosan derivative was produced, which was able to form
      a pH-responsive hydrogel.

PMID- 29455992
TI  - Nanosilver leverage on reactive dyeing of cellulose fibers: Color shading, color
      fastness and biocidal potentials.
AB  - The current approach focuses on studying the leverage of nanosilver (AgNPs)
      incorporation on the dyeing process of viscose fibers by blue reactive dye.
      Nanosilver was straightway incorporated into viscose fibers using sodium citrate
      as nanogenerator. Owing to AgNPs incorporation, color of fibers was turned to
      greenish-blue and darker greenish color was observed with low Ag content (<1
      g/kg). Regardless to the processes sequencing, color strength of fibers was
      magnified by increasing in Ag content. The constancy of fibers color was not
      affected by AgNPs inclusion, whatever the processes sequencing and Ag content.
      Release property of Ag from fibers into water was considerably depended on the
      processes sequencing. By incorporation of AgNPs firstly, the lowest Ag release
      value was estimated (0.25 g/kg after 24 h). Antimicrobial activities were
      significantly improved by AgNPs incorporation. Reduction in bacteria and fungi
      was reached 92.4% and 67.9% after 24 h contact time, respectively.

PMID- 29455993
TI  - Polysaccharide from Ostrea rivularis attenuates reproductive oxidative stress
      damage via activating Keap1-Nrf2/ARE pathway.
AB  - The purpose of this study was to investigate the effects of Ostrea rivularis
      polysaccharide (ORP) against testicular oxidative stress injury via kelch-like
      ECH-associated protein 1-nuclear erythroid 2-related factor 2/antioxidant
      response element (Keap1-Nrf2/ARE) pathway. In pharmacological experiments in
      vivo, ORP administration could dose-dependently inhibit body and testicular
      weight loss, ameliorate epididymal sperm quality and protect reproductive
      impairment in cyclophosphamide-induced male Balb/c mice. Moreover, the mechanism
      in vivo might be elucidated that ORP could increase expression level of Nrf2 and
      its downstream ARE gene battery in the testis, promote production of
      corresponding antioxidative enzymes and protein, and enhance Keap1-Nrf2/ARE
      signaling pathway to avoid male reproductive dysfunction. In addition, ORP
      treatment could improve survival capacity of H2O2-induced TM4 cells and its
      antioxidant mechanism in vitro also had been verified to activate Keap1-Nrf2/ARE
      signaling pathway. Overall, these results showed that ORP as a potent antioxidant
      could reduce reproductive oxidative stress damage related to Keap1-Nrf2/ARE
      pathway.

PMID- 29455994
TI  - Characterization of raw and alkali treated new natural cellulosic fiber from
      Coccinia grandis.L.
AB  - The physical, chemical, tensile, crystalline, thermal, and surface morphological
      properties of raw and alkali treated Coccinia Grandis.L Fibers (CGFs) were
      characterized for the first time in this work. The results of the chemical
      analysis indicate that, after alkali treatment, the cellulose content of CGFs
      increased whereas hemicelluloses, lignin and wax contents decreased. This
      directly influenced the tensile strength, crystallinity index, thermal stability
      and the roughness of alkali-treated CGFs. The thermal stability and activation
      energy of the CGFs improved from 213.4  degrees C to 220.6  degrees C and 67.02
      kJ/mol to 73.43 kJ/mol, respectively, due to alkali treatment. The statistical
      approach, Weibull distribution was adopted to analyze the tensile properties. The
      improved properties of the alkali treated CGF indicate that it could be an
      appropriate material for reinforcement in polymer composites.

PMID- 29455995
TI  - Investigations of benzo[a]pyrene encapsulation and Fenton degradation by starch
      nanoparticles.
AB  - Starch nanoparticles were produced by dialysis method from octenyl succinic
      anhydre (OSA) and 1,4-butane sultone (BS). The properties of the self-assembled
      nanoparticles were characterized by NMR spectroscopy (DOSY), fluorescence
      spectroscopy and dynamic light scattering (DLS). In order to investigate the
      formation of hydrophobic microdomains, the Nile Red dye was used as a fluorescent
      probe to evaluate the critical aggregation concentration (CAC) of modified starch
      in aqueous solution. The results show that the entrapment of the molecular guest
      was effective and only restricted by the solubility limit of the starch. Then,
      the modified starch was applied to solubilize benzo[a]pyrene (BaP) in view of
      degradation by Fenton process. Finally, it has been shown that 95% of BaP was
      degraded when it was encapsulated in OSA-BS-starch nanoparticles.

PMID- 29455996
TI  - Heterogeneous in situ polymerization of polyaniline (PANI) nanofibers on cotton
      textiles: Improved electrical conductivity, electrical switching, and tuning
      properties.
AB  - Electrically conductive cotton fabric was fabricated by in situ one pot oxidative
      polymerization of aniline. Using a simple heterogeneous polymerization method,
      polyaniline (PANI) nano fibers with an average fiber diameter of 40-75 nm were
      grafted in situ onto cotton fabric. The electrical conductivity of the PANI
      nanofiber grafted fabric was improved 10 fold compared to fabric grafted with
      PANI nanoclusters having an average cluster size of 145-315 nm. The surface
      morphology of the cotton fibers was characterized using SEM and AFM. Electrical
      conductivity of PANI nanofibers on the cotton textile was further improved from
      76 kOmega/cm to 1 kOmega/cm by increasing the HCl concentration from 1 M to 3 M
      in the polymerization medium. PANI grafted cotton fabrics were analyzed using
      FTIR, and the data showed the presence of polyaniline functional groups on the
      treated fabric. Further evidence was present for the chemical interaction of PANI
      with cellulose. Dopant level and morphology dependent electron transition
      behavior of PANI nanostructures grafted on cotton fabric was further
      characterized using UV-vis spectroscopy. The electrical conductivity of the PANI
      nano fiber grafted cotton fabric can be tuned by immersing the fabric in pH 2 and
      pH 6 solutions for multiple cycles.

PMID- 29455998
TI  - Cationic xylan- (2-methacryloyloxyethyl trimethyl ammonium chloride) polymer as a
      flocculant for pulping wastewater.
AB  - In this work, pulp mill wastewater was treated with a novel polymer flocculant,
      which was synthesized through polymerizing (2-methacryloyloxyethyl) trimethyl
      ammonium chloride (DMC) and xylan. Xylan-DMC polymer removed 94.5% of turbidity,
      61.7% of chemical oxygen demand (COD), 45.0% of lignin, 65.7% of sugar and 73.5%
      of biological oxygen demand (BOD) from the wastewater at the polymer
      concentration of 500 mg/L. The flocculation mechanism was fundamentally assessed
      with determining hydrodynamic size and chord length of flocs in the wastewater at
      different dosages of xylan-DMC polymer in the system. By adding polymers, the
      number of flocs with a small chord length (10-50 MUm) decreased, while that with
      a large chord length (150-300 MUm) increased, indicating the small particles
      agglomerated via bridging induced by the polymer. The sedimentation of formed
      flocs was quantitatively investigated by a vertical scan analyzer and the results
      depicted that the flocs could settle readily from the system.

PMID- 29455997
TI  - Effect of dynamic high pressure on emulsifying and encapsulant properties of
      cashew tree gum.
AB  - Dynamic high pressure (DHP) has been applied in the physical modification of
      biopolymers as polysaccharides, proteins and gums. It is known that DHP is able
      to promote degradation of polysaccharides (e.g. molecular weight reduction).
      However, few studies have assessed the effect of DHP on the emulsifying and
      encapsulating properties of polysaccharides. Thus, this study aimed to
      investigate the effect of DHP on the emulsifying (average droplet size and
      particle size distribution, optical and confocal scanning laser microscopy,
      rheology, zeta potential and electric conductivity, creaming index, and
      turbidity) and encapsulating (scanning electronic microscopy, flavor retention,
      average droplet size, and particle size distribution) properties of cashew tree
      gum (CG). The application of DHP process improved the emulsifying capacity of
      cashew tree gum (CG) by reducing the medium droplet size (D3,2 and D4,3),
      increasing the turbidity and improving the emulsion stability. However, no effect
      of DHP was observed on the encapsulating capacity of CG.

PMID- 29455999
TI  - Cellulaose acetate based thin film nanocomposite reverse osmosis membrane
      incorporated with TiO2 nanoparticles for improved performance.
AB  - In this work, cellulose acetate (CA) based thin film nanocomposite reverse
      osmosis (RO) membranes were fabricated using dissolution casting method by
      optimizing the CA/polyethylene glycol (CA/PEG-400) ratios for improved RO
      performance. The selectivity of optimized membrane was further enhanced by
      incorporating TiO2 (0-25 wt.%) nanoparticles. Fourier transform infrared
      spectroscopy (FTIR), thermogravimetric analyzer (TGA), scanning electron
      microscopy (SEM) and X-ray diffraction (XRD) were conducted to characterize
      control and modified membranes for the analysis of functional groups, thermal
      properties, morphology and structural investigation respectively. CP-2 of CA/PEG
      400 (80/20) was selected for further modification with TiO2 nanoparticles. The
      maximum salt rejection (95.4%) was observed for the membrane having 15% TiO2
      nanoparticles. Further escalation of TiO2 concentration resulted in the
      agglomeration of nanoparticles which subsequently decreased the permeation flux.
      The test results demonstrated that the modified membranes had higher salt
      rejection and chlorine resistance, lower degradation profile, successful
      inhibition of Escherichia coli growth and facilitating permeation flux compared
      to the control membrane.

PMID- 29456000
TI  - Preparation and characterization of poly(vinyl alcohol)/sodium alginate hydrogel
      with high toughness and electric conductivity.
AB  - Development of bio-based hydrogels with good mechanical properties and high
      electrical conductivity is of great importance for their excellent
      biocompatibility and biodegradability. Novel electrically conducive and tough
      poly(vinyl alcohol)/sodium alginate (PVA/SA) composite hydrogel was obtained by a
      simple method in this paper. PVA and SA were firstly dissolved in distilled water
      to form the composite solution and the pure PVA/SA hydrogel was obtained through
      the freezing/thawing process. The pure PVA/SA hydrogels were subsequently
      immersed into the saturated NaCl aqueous solution to increase the gel strength
      and conductivity. The effect of the immersing time on the thermal and mechanical
      properties of PVA/SA hydrogel was studied. The swelling properties and the
      antiseptic properties of the obtained PVA/SA hydrogel were also studied. This
      paper provided a novel way for the preparation of tough hydrogel electrolyte.

PMID- 29456001
TI  - Soluble soybean polysaccharide/TiO2 bionanocomposite film for food application.
AB  - In the current study, a set of biodegradable soybean polysaccharide (SSPS)
      nanocomposites containing different ratios of TiO2 nanoparticles was
      characterized as new packaging system. X-ray diffraction (XRD) measurement showed
      that the crystalline structure of the TiO2 nanoparticles remained intact in the
      polysaccharide matrix and the surface of nanocomposites containing 1-3% TiO2 was
      observed morphologically uniform under scanning electron microscopy (SEM).
      Dynamic mechanical thermal analysis revealed that the magnitude of storage
      modulus was 3.62-fold higher in SPSS/TiO2 nanocomposites containing 7 wt.% of
      TiO2 than control SSPS indicating improvement in the physical properties of the
      film supposed to be utilized for food packaging. With respect to the concern over
      the safety of these nanocomposites, inductively coupled plasma-optical emission
      spectroscopy (ICP-OES) showed that no TiO2 was detected in bread samples covered
      by SSPS/TiO2 film and stored for 6 months. Similarly, the nanocomposite films
      only released a minuscule amount (21.05 +/- 0.054 ppm) of TiO2 in water. TiO2
      nanoparticles were found in the plasma membrane of epithelial cell line after
      long-term exposure (10-day) of these cells to large amounts of the free
      nanoparticles. SSPS/TiO2 nanocomposites showed excellent antimicrobial activity
      against Staphylococcus aureus PTCC 1431 (ATCC 25923), while neither anti
      cancerous nor pro-cancerous activity was observed for these nanocomposites
      denoting their neutrality with respect to cancer suppression or progression in
      gastrointestinal tract. In conclusion, SSPS/TiO2 nanocomposites could be a
      promising packaging system for food industries' objective regarding their
      physical characteristics, low rate of Ti transition, and low health risk.

PMID- 29456002
TI  - Extraction and characterization of polysaccharides from tamarind seeds, rice mill
      residue, okra waste and sugarcane bagasse for its Bio-thermoplastic properties.
AB  - The aim of the present study is to extract potential thermoplastic
      polysaccharides from agricultural industrial wastes. Polysaccharides were
      extracted from renewable agro industrial wastes such as tamarind seeds [rich in
      starch (TSS)], okra head waste [rich in mucilage polysaccharide (OMP)], sugarcane
      bagasse [rich in cellulose (SBC)] and residual rice mill wastes [rich in starch
      and fiber (RS)]. Urigam variety of tamarind seed starch found to be an amylose
      rich starch. Different polysaccharides extracted from agro wastes were found to
      be having high thermal stability, except okra polysaccharide (comparatively low).
      X-ray diffraction pattern of tamarind seed starch proved its high crystallinity
      index. Crystallinity index of investigated polysaccharides were found to be in
      the order of SBC > TSS > RS > OMP. Chemical nature of extracted polysaccharides
      was confirmed by Fourier transform infrared spectroscopic analysis. Residual rice
      bran starch granules and tamarind seed starch globules were found to be having
      comparatively reduced particle size than sugarcane bagasse cellulose and okra
      mucilage. Scanning electron microscopic analysis revealed the cluster formations
      of RS granules and TSS globules. Residual rice bran starch found to be associated
      with other fibers (present in outer coat of rice). Okra mucilage and SBC were
      examined to be having linear sheets and linear bundles structures, respectively.

PMID- 29456003
TI  - Swallow root (Decalepis hamiltonii) pectic oligosaccharide (SRO1) induces cancer
      cell death via modulation of galectin-3 and survivin.
AB  - Swallow root pectic oligosaccharide fraction (SRO1) from swallow root pectic
      polysaccharide (SRPP) possessed a molecular size of 831 Da. Structural analysis
      revealed that it is a rhamnogalacturonan I type, bearing arabinogalactan side
      chain with beta-d-(1->4) galactose along with alpha-l-Araf (1->5)-alpha-l-Araf (1
      >3) structure on alpha-d-GalA-OAc-(1->2)-alpha-l-Rha-(1->4)- linear backbone.
      beta-d (1->4) linked galactose being the specific sugar for galectin-3, SRO1 had
      potentials in inhibiting galectin-3 mediated cancer progression. SRO1 inhibited
      galectin-3 mediated agglutination, in vitro, effectively with MIC of 1.08 MUg/ mL
      and down regulated mRNA levels of galectin-3 (~92%) along with its downstream key
      protein that inhibits apoptosis - survivin (~78%) suggesting the capability of
      SRO1 in inhibiting galectin-3 mediated cancer promoting pathway. This is the
      first report, which highlights the inhibition of interplay of galectin-3 and
      survivin by a dietary pectic oligosaccharide.

PMID- 29456004
TI  - The effect of oxyalkylation and application of polymer dispersions on the
      thermoformability and extensibility of paper.
AB  - Wood fiber-based packaging materials, as renewable materials, have growing market
      potential due to their sustainability. A new breakthrough in cellulose-based
      packaging requires some improvement in the mechanical properties of paper.
      Bleached softwood kraft pulp was mechanically treated, in two stages, using high-
      and low-consistency refining, sequentially. Chemical treatment of pulp using the
      oxyalkylation method was applied to modify a portion of fiber material,
      especially the fiber surface, and its compatibility with polymer dispersions
      including one carbohydrate polymer. The results showed that the compatibility of
      the cellulosic fibers with some polymers could be improved with oxyalkylation. By
      adjusting mechanical and chemical treatments, and the thermoforming conditions,
      the formability of paper was improved, but simultaneously the strength and
      stiffness decreased. The results suggest that the formability of the paper is not
      a direct function of the extensibility of the applied polymer, but also depends
      on the fiber network structure and surface energy.

PMID- 29456005
TI  - Bioconversion of chitosan into chito-oligosaccharides (CHOS) using family 46
      chitosanase from Bacillus subtilis (BsCsn46A).
AB  - BsCsn46A, a GH family 46 chitosanase from Bacillus subtilis had been previously
      shown to have potential for bioconversion of chitosan to chito-oligosaccharides
      (CHOS). However, so far, in-depth analysis of both the mode of action of this
      enzyme and the composition of its products were lacking. In this study, we have
      employed size exclusion chromatography, 1H NMR, and mass spectrometry to reveal
      that BsCsn46A can rapidly cleave chitosans with a wide-variety of acetylation
      degrees, using a non-processive endo-mode of action. The composition of the
      product mixtures can be tailored by varying the degree of acetylation of the
      chitosan and the reaction time. Detailed analysis of product profiles revealed
      differences compared to other chitosanases. Importantly, BsCsn46A seems to be one
      of the fastest chitosanases described so far. The detailed analysis of preferred
      endo-binding modes using H218O showed that a hexameric substrate has three
      productive binding modes occurring with similar frequencies.

PMID- 29456006
TI  - Effective cellulose nanocrystal imaging using transmission electron microscopy.
AB  - Characterization of cellulose nanocrystals (CNCs) is often complex and tedious.
      With their increased use for biological materials, polymer reinforcing agents,
      and other applications, better characterization methods of CNCs are needed to
      ensure product quality. However, because of their small size, hydrogen bonding,
      and low electron density, individual CNCs are difficult to image with high
      resolution and magnification using electron microscopy. Methods to help counter
      these challenges include staining for increased contrast and techniques to
      increase dispersion. This work tested several stains, dispersing agents, and
      sample supports to find a consistent method of individualizing CNCs and providing
      good contrast for imaging in transmission electron microscopy (TEM). The most
      consistent method found uses a low concentration of CNCs, bovine serum albumin as
      a dispersing agent, and Nanovan(r) as the contrasting stain on a silicon monoxide
      coated Formvar TEM grid.

PMID- 29456007
TI  - Fucosylated chondroitin sulfate is covalently associated with collagen fibrils in
      sea cucumber Apostichopus japonicus body wall.
AB  - Fucosylated chondroitin sulfate (fCS) is the major carbohydrate constituent of
      sea cucumber. However, the distribution of fCS in the sea cucumber body wall has
      not been fully described. We addressed this in the present study employing
      Apostichopus japonicus as the material, a sea cucumber species with significant
      commercial importance. It was found that fCS was covalently attached to collagen
      fibrils via O-glycosidic linkages. Transmission electron microscopy analysis
      revealed that fCS precipitate was present in gap regions of collagen fibrils as
      roughly globular or ellipsoidal dots. The fCS dots arranged circumferentially
      around the fibrils with an axial repeat period that matched the periodicity of
      the fibrils. Physicochemical analysis indicated that the presence of fCS
      significantly increased the negative charge of the fibrils. These findings
      provide novel insight into fCS distribution in the sea cucumber body wall and its
      supramolecular organization with other macromolecules.

PMID- 29456008
TI  - Ion-assisted fabrication of neutral protein crosslinked sodium alginate nanogels.
AB  - Protein crosslinked nanogels which combine the merits of nanogels and the
      specific biological activity from protein have emerged as fascinating protein
      delivery systems. However, the fragility and low density of reactive group in
      proteins, especially low electric density of neutral proteins seriously limited
      the fabrication of protein crosslinked nanogels without affecting their
      bioactivities. Here, we demonstrated a facile ion-assisted method to fabricate
      neutral protein crosslinked nanogels. Oxidized sodium alginate (OSA) with
      aldehyde groups and low viscosity was successfully synthesized, which could
      reversibly form nanogels via addition and removal of divalent cation.
      Subsequently, hemoglobin and myoglobin were used as representative neutral
      proteins to fabricate stable protein crosslinked OSA nanogels under the assist of
      divalent cation followed by in situ Schiff base formation between OSA and
      proteins. The mild fabrication condition guaranteed the structural integrity and
      bioactivity of proteins in the obtained protein crosslinked nanogels. This ion
      assisted method was expected to bring a new opportunity for fabricating versatile
      functional biohybrid nanogels systems.

PMID- 29456009
TI  - Novel in situ forming hydrogel based on xanthan and chitosan re-gelifying in
      liquids for local drug delivery.
AB  - Injectable hydrogels have been an attractive topic in biomaterials. However,
      during gelation in vivo, they are easy to disperse due to tissue exudates, thus
      leading to failure of controlled drug release. To solve this problem, we present
      a novel polysaccharide-based injectable hydrogel via self-crosslinking of
      aldehyde-modified xanthan (Xan-CHO) and carboxymethyl-modified chitosan (NOCC).
      The physical properties were optimized by adjusting the mass ratio of Xan-CHO and
      NOCC. Experiments revealed that this material exhibited the characteristics of
      self-healing, anti-enzymatic hydrolysis, biocompatibility and biodegradability.
      The releasing curve demonstrated stable release of BSA-FITC within 10 h after
      injection in liquids. After incorporation with a vascular endothelial growth
      factor, there was an interaction between this biomaterial and the host, which
      accelerated the reconstruction of the abdominal wall in rats. Therefore, this
      injectable hydrogel, as a drug delivery system, can prevent drug outburst in a
      variety of settings and function as a tissue scaffold.

PMID- 29456010
TI  - Extraction and characterization of arrowroot (Maranta arundinaceae L.) starch and
      its application in edible films.
AB  - This research work aimed extraction and characterization of arrowroot starch.
      Besides, the effects of different concentrations of starch (2.59-5.41%,
      mass/mass) and concentrations of glycerol (9.95-24.08%, mass versus starch mass)
      on films properties were evaluated by a rotational central composite 22
      experimental design. Arrowroot starch showed high amylose content (35%). Low
      values were found for the swelling power and solubility index. The X-ray
      diffraction showed "C" type crystalline structures, while thermogram showed Tg
      around of 118 and 120  degrees C. The thermogravimetric analysis showed that 40%
      of mass loss of starch occurred between 330 and 410  degrees C. The films were
      homogeneous, transparent and manageable. Starch and glycerol concentrations
      played a significant role in thickness and solubility in water of films, but was
      not significant for water vapor permeability and tensile strength. Therefore,
      arrowroot is a very promising starch source for application in films.

PMID- 29456011
TI  - Effect of retention rate of fluorescent cellulose nanofibrils on paper properties
      and structure.
AB  - In this work, we report a new characterization method using fluorescent cellulose
      nanofibrils to analyze retention and loss rates in the papermaking process.
      Cellulose nanofibrils (CNF) were isolated from chemical pulp by enzymatic
      pretreatment and used as a strengthening additive in sheet forming. The aim of
      this paper was to investigate its effects on flocculation, retention and loss
      rate and the physical and mechanical properties. CNF was subjected to fluorescent
      labeling with RBITC (Rhodamine B isothiocyanate), and the retention of
      fluorescent cellulose nanofibrils (FCNF) was analyzed by elemental analysis and
      fluorescence intensity. The retention and loss rate of the FCNF decreased with
      increasing the addition of FCNF. Laser Confocal Scanning Microscopy (LCSM) and
      Scanning Electron Microscope (SEM) images confirmed that FCNF can be evenly
      distributed in the paper. A thorough investigation of the relation between the
      retention rate and papersheet performance was conducted.

PMID- 29456012
TI  - Injectable and body temperature sensitive hydrogels based on chitosan and
      hyaluronic acid for pH sensitive drug release.
AB  - Hydrogels based on chitosan/hyaluronic acid/beta-sodium glycerophosphate
      demonstrate injectability, body temperature sensitivity, pH sensitive drug
      release and adhesion to cancer cell. The drug (doxorubicin) loaded hydrogel
      precursor solutions are injectable and turn to hydrogels when the temperature is
      increased to body temperature. The acidic condition (pH 4.00) can trigger the
      release of drug and the cancer cell (Hela) can adhere to the surface of the
      hydrogels, which will be beneficial for tumor site-specific administration of
      drug. The mechanical strength, the gelation temperature, and the drug release
      behavior can be tuned by varying hyaluronic acid content. The mechanisms were
      characterized using dynamic mechanical analysis, Fourier transform infrared
      spectroscopy, scanning electron microscopy and fluorescence microscopy. The
      carboxyl group in hyaluronic acid can form the hydrogen bondings with the
      protonated amine in chitosan, which promotes the increase of mechanical strength
      of the hydrogels and depresses the initial burst release of drug from the
      hydrogel.

PMID- 29456013
TI  - Oxidation pattern of curdlan with TEMPO-mediated system.
AB  - In this study, the TEMPO-mediated (TEMPO/NaBr/NaClO) oxidation pattern of curdlan
      was investigated through comprehensively structural analysis of the corresponding
      oxidized products. During the structural analysis, infrared spectroscopy (IR),
      nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography
      tandem multiple angle laser scattering (GPC-MALS) and ultra-high performance
      liquid chromatography tandem quadrupole time of flight mass spectrometry (UHPLC
      Q/TOF-MS) were applied. As a result, the homogenous beta1-3 polyglucuronic acids
      (MW, 49.8, 29.8 and 7.0 kDa) were obtained with proper amount of oxidant (5.36
      mmol NaClO) at various temperatures (4, 25, 50  degrees C), respectively.
      Compared to the oxidation of 1-4 linked glucan (starch and cellulose) with TEMPO
      mediated system at same reaction conditions, higher degree of specific oxidation
      and less degradation were observed in that of 1-3 linked curdlan. The
      glycosylation at position 3 could stabilize the sugar ring, which inactivates the
      non-specific oxidation related hydroxyl groups on the sugar ring. Thus, the TEMPO
      mediated system has higher selectivity to oxidize the primary hydroxyl groups of
      1-3 linked curdlan and form polyglucuronic acid than those observed in the
      oxidation of starch and cellulose. In addition, same as those observed in
      previous work about starch, higher the temperature was used in the oxidation with
      TEMPO system, higher the activity of oxidant (NaClO solution) was, more non
      specific oxidation occurred, and more the degradation were observed.

PMID- 29456014
TI  - Structural characterization of polysaccharides from Cabernet Franc, Cabernet
      Sauvignon and Sauvignon Blanc wines: Anti-inflammatory activity in LPS stimulated
      RAW 264.7 cells.
AB  - The structural characterization of the polysaccharides and in vitro anti
      inflammatory properties of Cabernet Franc (WCF), Cabernet Sauvignon (WCS) and
      Sauvignon Blanc (WSB) wines were studied for the first time in this work. The
      polysaccharides of wines gave rise to three fractions of polysaccharides, namely
      (WCF) 0.16%, (WCS) 0.05% and (WSB) 0.02%; the highest one was chosen for
      isolation of polysaccharides (WCF). It was identified the presence of mannan,
      formed by a sequence of alpha-d-Manp (1 -> 6)-linked and side chains O-2
      substituted for alpha-d-mannan (1 -> 2)-linked; type II arabinogalactan, formed
      by (1 -> 3)-linked beta-d-Galp main chain, substituted at O-6 by (1 -> 6)-linked
      beta-d-Galp side chains, and nonreducing end-units of arabinose 3-O-substituted;
      type I rhamnogalacturonan formed by repeating (1 -> 4)-alpha-d-GalpA-(1 -> 2)
      alpha-L-Rhap groups; and traces of type II rhamnogalacturonan. The polysaccharide
      mixture and isolated fractions inhibited the production of inflammatory cytokines
      (TNF-alpha and IL-1beta) and mediator (NO) in RAW 264.7 cells stimulated with
      LPS.

PMID- 29456015
TI  - Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral
      and cell-mediated immunity.
AB  - A cytomegalovirus (CMV) vaccine that is effective at preventing congenital
      infection and reducing CMV disease in transplant patients remains a high priority
      as no approved vaccines exist. While the precise correlates of protection are
      unknown, neutralizing antibodies and antigen-specific T cells have been
      implicated in controlling infection. We demonstrate that the immunization of mice
      and nonhuman primates (NHPs) with lipid nanoparticles (LNP) encapsulating
      modified mRNA encoding CMV glycoproteins gB and pentameric complex (PC) elicit
      potent and durable neutralizing antibody titers. Since the protective correlates
      in pregnant women and transplant recipients may differ, we developed an
      additional mRNA vaccine expressing the immunodominant CMV T cell antigen pp65.
      Administration of pp65 vaccine with PC and gB elicited robust multi-antigenic T
      cell responses in mice. Our data demonstrate that mRNA/LNP is a versatile
      platform that enables the development of vaccination strategies that could
      prevent CMV infection and consequent disease in different target populations.

PMID- 29456016
TI  - Monoclonal antibody based in vitro potency assay as a predictor of antigenic
      integrity and in vivo immunogenicity of a Respiratory Syncytial Virus post-fusion
      F-protein based vaccine.
AB  - The post-fusion form of Respiratory Syncytial Virus (RSV) fusion (F) protein has
      been used recently in clinical trials as a potential vaccine antigen with the
      objective of eliciting protective immune response against RSV. In this paper, in
      vitro antigenicity and in vivo immunogenicity of recombinant, soluble F protein
      of RSV (RSVsF) were evaluated by several assays. In Vitro Relative Potency (IVRP)
      of RSVsF was measured in a sandwich ELISA using two antibodies, each specific for
      epitope site A or C. Therefore, IVRP reflected the integrity of the antigen in
      terms of changes in antibody binding affinity of either or both of these sites.
      RSVsF samples with a wide range of IVRP values were generated by applying UV
      irradiation (photo) and high temperature (heat) induced stress for varying
      lengths of time. These samples were characterized in terms of stress induced
      modifications in primary and secondary structures as well as aggregation of
      RSVsF. Immunogenicity, also referred to as In vivo potency, was measured by
      induction of total F-protein specific IgG and RSV-neutralizing antibodies in mice
      dosed with these RSVsF samples. Comparison of results between IVRP and these
      immunogenicity assays revealed that IVRP provided a sensitive read-out of the
      integrity of epitope sites A and C, and a conservative and reliable evaluation of
      the potency of RSVsF as a vaccine antigen. This high throughput and fast turn
      around assay allowed us to efficiently screen many different RSVsF antigen lots,
      thereby acting as an effective filter for ensuring high quality antigen that
      delivered in vivo potency. In vitro and in vivo potencies were further probed at
      the level of individual epitope sites, A and C. Results of these experiments
      indicated that site A was relatively resistant to stress induced loss of potency,
      in vitro or in vivo, compared to site C.

PMID- 29456017
TI  - Myocarditis and pericarditis are rare following live viral vaccinations in
      adults.
AB  - Reports of myocarditis and pericarditis following smallpox vaccination in adults
      suggested a need to assess inflammatory cardiac disease risk among adults who
      receive live viral vaccinations. From 1996 through 2007, among 416,629 vaccinated
      adults in the Vaccine Safety Datalink, we identified one probable pericarditis
      case and no cases of myocarditis in the 42 days following a live viral
      vaccination. Our self-controlled risk interval analysis found that, based on one
      case identified during the risk interval and 10 cases during the control
      interval, there is no increased risk of myopericarditis in the 42 days following
      vaccination (IRR, 0.57; 95% CI, 0.07, 4.51). Our study suggests that the
      occurrence of myopericarditis following live viral vaccination is rare with an
      estimated incidence of 0.24 per 100,000 vaccinated, which is not higher than the
      background rate and is much lower than the incidence rates reported following
      smallpox vaccination.

PMID- 29456018
TI  - Key steps forward for maternal immunization: Policy making in action.

PMID- 29456019
TI  - Exosomes Serve as Nanoparticles to Deliver Anti-miR-214 to Reverse
      Chemoresistance to Cisplatin in Gastric Cancer.
AB  - Chemoresistance is one of the causes of adverse effects in gastric cancer,
      including a poor response to cisplatin (DDP). Exosomes loaded with microRNA
      (miRNA), mRNA, and other non-coding RNAs could regulate drug resistance. Exo-anti
      214 was extracted and verified. A Cell Counting Kit-8 (CCK-8) cell viability
      assay, flow cytometry, and transwell and immunofluorescence assays were performed
      to determine whether exo-anti-214 could sensitize cells to DDP in vitro. A
      combination of intravenously injected exo-anti-214 and intraperitoneal DDP was
      utilized in vivo. Additionally, potential targets of miR-214 were screened by
      mass spectrometry (MS) and confirmed via western blotting (WB). The levels of miR
      214 in the human immortalized gastric epithelial cell line ges-1 and the human
      gastric adenocarcinoma cell lines SGC7901 and SGC7901/DDP gradually increased.
      Exo-anti-214 could fuse with cells and regulate potential targets, reducing cell
      viability, suppressing migration, and promoting apoptosis in vitro. Caudally
      injected exo-anti-214 was applied to reverse chemoresistance and repress tumor
      growth in vivo due to the downregulation of miR-214 and overexpression of
      possible target proteins in tumors. Exo-anti-214 could reverse the resistance to
      DDP in gastric cancer, which might serve as a potential alternative for the
      treatment of cisplatin-refractory gastric cancer in the future.

PMID- 29456020
TI  - Advanced siRNA Designs Further Improve In Vivo Performance of GalNAc-siRNA
      Conjugates.
AB  - Significant progress has been made in the advancement of RNAi therapeutics by
      combining a synthetic triantennary N-acetylgalactosamine ligand targeting the
      asialoglycoprotein receptor with chemically modified small interfering RNA
      (siRNA) designs, including the recently described Enhanced Stabilization
      Chemistry. This strategy has demonstrated robust RNAi-mediated gene silencing in
      liver after subcutaneous administration across species, including human. Here we
      demonstrate that substantial efficacy improvements can be achieved through
      further refinement of siRNA chemistry, optimizing the positioning of 2'-deoxy-2'
      fluoro and 2'-O-methyl ribosugar modifications across both strands of the double
      stranded siRNA duplex to enhance stability without compromising intrinsic RNAi
      activity. To achieve this, we employed an iterative screening approach across
      multiple siRNAs to arrive at advanced designs with low 2'-deoxy-2'-fluoro content
      that yield significantly improved potency and duration in preclinical species,
      including non-human primate. Liver exposure data indicate that the improvement in
      potency is predominantly due to increased metabolic stability of the siRNA
      conjugates.

PMID- 29456022
TI  - Comments on: "Positive Effects of Extracorporeal Shock Wave Therapy on Spasticity
      in Post-Stroke Patients: A Meta-Analysis".

PMID- 29456021
TI  - Brain Nat8l Knockdown Suppresses Spongiform Leukodystrophy in an Aspartoacylase
      Deficient Canavan Disease Mouse Model.
AB  - Canavan disease, a leukodystrophy caused by loss-of-function ASPA mutations, is
      characterized by brain dysmyelination, vacuolation, and astrogliosis ("spongiform
      leukodystrophy"). ASPA encodes aspartoacylase, an oligodendroglial enzyme that
      cleaves the abundant brain amino acid N-acetyl-L-aspartate (NAA) to L-aspartate
      and acetate. Aspartoacylase deficiency results in a 50% or greater elevation in
      brain NAA concentration ([NAAB]). Prior studies showed that homozygous
      constitutive knockout of Nat8l, the gene encoding the neuronal NAA synthesizing
      enzyme N-acetyltransferase 8-like, prevents aspartoacylase-deficient mice from
      developing spongiform leukodystrophy. We now report that brain Nat8l knockdown
      elicited by intracerebroventricular/intracisternal administration of an adeno
      associated viral vector carrying a short hairpin Nat8l inhibitory RNA to neonatal
      aspartoacylase-deficient AspaNur7/Nur7 mice lowers [NAAB] and suppresses
      development of spongiform leukodystrophy.

PMID- 29456023
TI  - Alternative Mode of E-Site tRNA Binding in the Presence of a Downstream mRNA Stem
      Loop at the Entrance Channel.
AB  - Structured mRNAs positioned downstream of the ribosomal decoding center alter
      gene expression by slowing protein synthesis. Here, we solved the cryo-EM
      structure of the bacterial ribosome bound to an mRNA containing a 3' stem loop
      that regulates translation. Unexpectedly, the E-site tRNA adopts two distinct
      orientations. In the first structure, normal interactions with the 50S and 30S E
      site are observed. However, in the second structure, although the E-site tRNA
      makes normal interactions with the 50S E site, its anticodon stem loop moves ~54
      A away from the 30S E site to interact with the 30S head domain and 50S uL5. This
      position of the E-site tRNA causes the uL1 stalk to adopt a more open
      conformation that likely represents an intermediate state during E-site tRNA
      dissociation. These results suggest that structured mRNAs at the entrance channel
      restrict 30S subunit movement required during translation to slow E-site tRNA
      dissociation.

PMID- 29456024
TI  - Protective Effects of Flagellin A N/C Against Radiation-Induced NLR Pyrin Domain
      Containing 3 Inflammasome-Dependent Pyroptosis in Intestinal Cells.
AB  - PURPOSE: To investigate changes induced in mouse intestines after irradiation and
      to explore the potential radioprotective effects of flagellin A N/C (FlaAN/C).
      METHODS AND MATERIALS: A mouse model of radiation-induced enteropathy was used in
      this study. A 10-Gy abdominal irradiation was performed on FlaAN/C- and vehicle
      injected mice to explore the role of FlaAN/C in intestinal radiation injury and
      to study the molecular mechanism in this process. In the intestinal tissue,
      pathologic changes were investigated by hematoxylin and eosin staining, TUNEL
      staining, and immunohistochemistry; Western blotting and quantitative reverse
      transcription-polymerase chain reaction were used to determine the changes in
      protein and messenger RNA levels, respectively; and an enzyme-linked
      immunosorbent assay was performed to determine protein concentration in serum.
      The involvement of the reactive oxygen species pathway was investigated by
      determining superoxide dismutase, glutathione (GSH) peroxidase, GSH reductase,
      and GSH disulfide (GSSG) plus GSH activities. RESULTS: Flagellin A N/C inhibited
      radiation-induced reactive oxygen species production, decreased NLRP3 activity,
      and reduced the occurrence of caspase-1-dependent pyroptosis. The results
      revealed that oxidative stress, bioenergetic impairment, and subsequent NLRP3
      inflammasome activation were involved in radiation-induced intestinal injury.
      Flagellin A N/C exerted a protective effect by blunting the activation of NLRP3
      inflammasome signaling, thereby reducing the inflammatory response and occurrence
      of caspase-1-dependent pyroptosis in the intestine. Therefore, treatment of mice
      with FlaAN/C reduced radiation-induced intestinal injury. CONCLUSIONS: Reactive
      oxygen species-induced NLRP3 inflammasomes mediated radiation-induced pyroptosis
      of the intestinal cells, and FlaAN/C suppressed pyroptosis to protect the
      intestinal tissue. These results provide novel insights into the mechanisms
      underlying radiation-induced cytotoxicity, and FlaAN/C might be a potential
      preventive therapy for radiation-induced intestinal injury in patients with
      cancer.

PMID- 29456025
TI  - Effectiveness of User- and Expert-Driven Web-based Hypertension Programs: an RCT.
AB  - INTRODUCTION: The effectiveness of self-guided Internet-based lifestyle
      counseling (e-counseling) varies, depending on treatment protocol. Two dominant
      procedures in e-counseling are expert- and user-driven. The influence of these
      procedures on hypertension management remains unclear. The objective was to
      assess whether blood pressure improved with expert-driven or user-driven e
      counseling over control intervention in patients with hypertension over a 4-month
      period. STUDY DESIGN: This study used a three-parallel group, double-blind
      randomized controlled design. SETTING/PARTICIPANTS: In Toronto, Canada, 128
      participants (aged 35-74 years) with hypertension were recruited. Participants
      were recruited using online and poster advertisements. Data collection took place
      between June 2012 and June 2014. Data were analyzed from October 2014 to December
      2016. INTERVENTION: Controls received a weekly e-mail newsletter regarding
      hypertension management. The expert-driven group was prescribed a weekly exercise
      and diet plan (e.g., increase 1,000 steps/day this week). The user-driven group
      received weekly e-mail, which allowed participants to choose their intervention
      goals (e.g., [1] feel more confident to change my lifestyle, or [2] self-help
      tips for exercise or a heart healthy diet). MAIN OUTCOME MEASURES: Primary
      outcome was systolic blood pressure measured at baseline and 4-month follow-up.
      Secondary outcomes included cholesterol, 10-year Framingham cardiovascular risk,
      daily steps, and dietary habits. RESULTS: Expert-driven groups showed a greater
      systolic blood pressure decrease than controls at follow-up (expert-driven versus
      control: -7.5 mmHg, 95% CI= -12.5, -2.6, p=0.01). Systolic blood pressure
      reduction did not significantly differ between user- and expert-driven. Expert
      driven compared with controls also showed a significant improvement in pulse
      pressure, cholesterol, and Framingham risk score. The expert-driven intervention
      was significantly more effective than both user-driven and control groups in
      increasing daily steps and fruit intake. CONCLUSIONS: It may be advisable to
      incorporate an expert-driven e-counseling protocol in order to accommodate
      participants with greater motivation to change their lifestyle behaviors, but
      more studies are needed. TRIAL REGISTRATION: This study is registered at
      www.clinicaltrials.gov NCT03111836.

PMID- 29456027
TI  - Enhanced chondrogenesis differentiation of human induced pluripotent stem cells
      by MicroRNA-140 and transforming growth factor beta 3 (TGFbeta3).
AB  - Induced pluripotent stem cells (iPSCs) make an attractive source for regenerative
      medicine. The objective of our study was to establish a new method for
      differentiation of human iPSCs toward chondrocyte by overexpression of MicroRNA
      140 (miR-140) and use of transforming growth factor beta 3 (TGFbeta3) in high
      cell density culture systems. We prepared vectors and then was used for
      recombinant Lenti virus production in HEK-293 cell. Transducted cells were
      selected and cultured in pellet culture system and were harvested after days 7,
      14 and 21. Real-time PCR was performed to evaluate the cartilage-specific genes
      in the mRNA levels. Also, in order to confirm our results, we have done
      immunological assay. iPSCs were transducted with recombinant Lenti virus and miR
      140 was expressed. Immunological methods confirmed that differentiation of iPSC
      toward chondrocyte with handling cartilage matrix genes. Also real time PCR
      demonstrated that in transducted iPSCs significantly increased gene expression of
      collagen type II, SOX9 and aggrecan, and down-regulated expression of collagen
      type I when compared to the mRNA levels measured in non transducted iPSCs. In
      Conclusion, our data implies that miR-140 is a potent chondrogenic
      differentiation inducer for iPSCs and also, we have showed increasing
      chondrogenic differentiation by using overexpression of miR-140 and TGFbeta3.

PMID- 29456026
TI  - Neural Population Dynamics Underlying Motor Learning Transfer.
AB  - Covert motor learning can sometimes transfer to overt behavior. We investigated
      the neural mechanism underlying transfer by constructing a two-context paradigm.
      Subjects performed cursor movements either overtly using arm movements, or
      covertly via a brain-machine interface that moves the cursor based on motor
      cortical activity (in lieu of arm movement). These tasks helped evaluate whether
      and how cortical changes resulting from "covert rehearsal" affect overt
      performance. We found that covert learning indeed transfers to overt performance
      and is accompanied by systematic population-level changes in motor preparatory
      activity. Current models of motor cortical function ascribe motor preparation to
      achieving initial conditions favorable for subsequent movement-period neural
      dynamics. We found that covert and overt contexts share these initial conditions,
      and covert rehearsal manipulates them in a manner that persists across context
      changes, thus facilitating overt motor learning. This transfer learning mechanism
      might provide new insights into other covert processes like mental rehearsal.

PMID- 29456029
TI  - Letter in response to the article entitled "Assessing the relationship between a
      body shape index and mortality in a group of middle-aged men".

PMID- 29456028
TI  - Polyphasic characterization of a novel species in the Lactobacillus casei group
      from cow manure of Taiwan: Description of L. chiayiensis sp. nov.
AB  - Two Gram-stain-positive, rod-shaped, non-motile, catalase-negative and
      facultative anaerobic strains, NCYUAST and BCRC 18859 (=NRIC 1947), were isolated
      from cow manure of Taiwan and coconut juice of Philippines, respectively.
      Comparative sequence analysis of 16S rRNA gene revealed that the novel strains
      were members of the genus Lactobacillus. These two strains had 100% of 16S rRNA
      gene sequence similarity and 98.6% of average nucleotide identity (ANI) value
      based on whole genome sequences. On the basis of 16S rRNA gene sequence
      similarity, the type strains of Lactobacillus casei (99.6% similarity),
      Lactobacillus paracasei subsp. paracasei (99.1%), L. paracasei subsp. tolerans
      (99.1%), Lactobacillus rhmnosus (99.0%) and 'Lactobacillus zeae' (99.7%) were the
      closest neighbors to these novel strains. The results of phenotypic and
      chemotaxonomic characterization, multilocus sequence analysis (MLSA) based on the
      sequences of three housekeeping genes (dnaK, pheS and yycH), whole-genome
      sequence (WGS)-based comparison by ANI and in silico DNA-DNA hybridization
      (isDDH), species-specific PCR and whole-cell MALDI-TOF MS spectral pattern
      analyses demonstrated that the novel two strains represented a single, novel
      species within the L. casei group, for which the name Lactobacillus chiayiensis
      sp. nov., is proposed. The type strain is NCYUAST (=BCRC 81062T=NBRC 112906T).

PMID- 29456030
TI  - Acute phase nutritional screening tool associated with functional outcomes of hip
      fracture patients: A longitudinal study to compare MNA-SF, MUST, NRS-2002 and
      GNRI.
AB  - BACKGROUND & AIMS: Several hip fracture patients are malnourished, but no study
      has attempted to determine the optimal nutritional screening tool for predicting
      functional outcomes. We investigated the association between each nutritional
      status assessed by four nutritional screening tools at admission and functional
      outcomes during the postoperative acute phase in hip fracture patients. METHODS:
      The Mini Nutritional Assessment-Short Form (MNA-SF), the Malnutrition Universal
      Screening Tool (MUST), the Nutritional Risk Score 2002 (NRS-2002) and the
      Geriatric Nutritional Risk Index (GNRI) were assessed at admission before
      surgery. We evaluated the motor domain of the functional independence measure
      (motor-FIM) score at discharge, efficiency on the motor-FIM (change in the motor
      FIM score after postoperative rehabilitation divided by postoperative length of
      hospital stay), and 10-m walking speed at postoperative 14 days as functional
      outcomes. RESULTS: Two hundred and five patients (mean patient age, 83.5 +/- 7.0
      years; range, 65-100 years; 82% female) were included. The MNA-SF evaluation
      classified 56 patients as well-nourished, 103 as at risk of malnutrition and 46
      as malnourished. The MUST evaluation classified 97 patients as low risk, 42 as
      medium risk and 66 as high risk. The NRS-2002 evaluation classified 89 patients
      as well-nourished, 69 as medium risk and 47 as nutritionally at risk. The GNRI
      evaluation classified 44 patients as no risk, 74 as low risk and 87 as a major
      risk. Multiple linear regression analysis revealed that MNA-SF had a significant
      association with discharge motor-FIM (well-nourished vs. at risk of malnutrition,
      standardised beta = -0.06, p = 0.04; vs. malnourished, standardised beta = -0.32,
      p < 0.01), efficiency on the motor-FIM (well-nourished vs. malnourished,
      standardised beta = -0.19, p = 0.02) and 10-m walking speed (well-nourished vs.
      malnourished, standardised beta = -0.30, p < 0.01). The GNRI was significantly
      associated with 10-m walking speed (no risk vs. mild risk, standardised beta = 
      0.23, p = 0.02; vs. major risk, standardised beta = -0.37, p < 0.01), but not of
      motor-FIM and efficiency on the motor-FIM. No significant relationships were
      found among MUST and NRS-2002 and any functional outcomes. CONCLUSIONS: The MNA
      SF was found to be an optimal nutritional screening tool to associate with
      functional outcomes during the postoperative acute phase of elderly hip fracture
      patients.

PMID- 29456031
TI  - Re: Comment on "Assessing the relationship between a body shape index and
      mortality in a group of middle-aged men".

PMID- 29456032
TI  - Superiority of new predictive equation for resting energy expenditure should be
      reconsidered.

PMID- 29456033
TI  - Ecostructuring of marine nematode communities by submarine groundwater discharge.
AB  - Inputs of submarine groundwater discharge (SGD) to the coastal ocean may alter
      local and regional-scale biology. Here, we report on nematode assemblages along
      the north shore of Long Island, NY. We test if nematode communities differed
      between sites impacted by mixed fresh-saline SGD and where SGD is exclusively
      saline. Diversity of nematodes was low at sites impacted by fresh SGD and
      communities were dominated by a few opportunistic genera. Moreover, a set of
      typical freshwater nematode genera restricted to impacted sites was observed.
      Their presence in the marine coastal zone is exceptional and underlines the
      structuring role that fresh SGD plays in the local ecosystem. Saline SGD
      structured nematode assemblages differently compared to sites impacted by fresh
      SGD. The number of nematode genera was markedly higher at saline SGD sites, with
      a different community structure. This study highlights the importance to which
      inputs of fresh SGD may have on local ecosystem diversity in marine coastal
      environments.

PMID- 29456034
TI  - Cryopreservation and storage of cat epididymal sperm using -75  degrees C freezer
      vs liquid nitrogen.
AB  - The quality of cat epididymal sperm cryopreserved and stored by four methods was
      assessed. Epididymal sperm were suspended in Tris-glucose-citrate egg yolk
      extender, loaded in 0.25 mL straws and then cryopreserved. The samples in a
      standard protocol (LN) were cryopreserved and stored in liquid nitrogen (LN2).
      The sperm straws in the LN-Fr-LN group were cryopreserved in LN2 and stored in a 
      75  degrees C freezer; the straws were returned to LN2 prior to thawing. The
      loaded straws in the Fr group were transferred directly from 4  degrees C to the
      freezer and maintained in the freezer until thawing. The Fr-LN samples were
      cryopreserved and stored in the freezer and were introduced into LN2 before
      thawing. The sperm thawing was conducted on days 30, 60, 90 and 120 of
      cryopreservation. The sperm motility, viability, membrane integrity and acrosome
      integrity were evaluated at 15 and 180 min after thawing. The quality of post
      thaw sperm in all three modified protocols was comparable (P > 0.05) and did not
      differ from that in the standard protocol except the membrane integrity of the 60
      days stored samples evaluated at 15 min after thawing, which was significantly
      higher for the LN-Fr-LN than the Fr-LN groups (P = 0.04). The length of
      cryopreservation time had no effect (P > 0.05) on the sperm parameters assessed
      at 15 min after thawing. The sperm motility was significantly greater (P = 0.01
      to P = 0.02) for the 15 min than the 180 min incubation. In conclusion, cat
      epididymal sperm could alternatively be cryopreserved and/or stored by using the 
      75  degrees C freezer for 120 days. To use, the cryopreserved sperm in the
      freezer could be thawed immediately or after being transferred to LN2. This was
      useful for the application of the -75  degrees C cryopreserved sperm in remote
      areas.

PMID- 29456035
TI  - A Comparison of the Efficacy of Immunomodulatory-containing Regimens in
      Relapsed/Refractory Multiple Myeloma: A Network Meta-analysis.
AB  - BACKGROUND: Previous network meta-analyses combined studies of immunomodulatory
      drug (IMiD)-containing and IMiD-free regimens, despite a lack of head-to-head
      randomized controlled trials to robustly link them. However, patients with
      relapsed or refractory multiple myeloma (RRMM) treated with IMiD-containing
      regimens differ from those treated with IMiD-free regimens, especially relating
      to treatment history, which is an important treatment-effect modifier requiring
      clinical consideration when evaluating the most appropriate subsequent treatment
      options. A need exists to separately assess the efficacy of treatment regimens
      for patients who are suitable candidates for IMiD-containing and IMiD-free
      regimens. The presented analyses will enable clinicians to assess the best
      regimens to use in patients suitable for IMiD-containing regimens. MATERIALS AND
      METHODS: We used a Bayesian network meta-analysis to compare IMiD-containing
      regimens in patients with RRMM. Additionally, subgroup analyses were conducted
      stratified by previous therapy line, previous bortezomib therapy, and previous
      lenalidomide therapy. RESULTS: The results indicated that triplet combinations
      are more effective than doublet combinations. Of the triplet combinations,
      daratumumab, lenalidomide, dexamethasone (DRd) was significantly better in
      improving progression-free survival in patients with RRMM than were other IMiD
      containing regimens (lenalidomide, dexamethasone [Rd]: hazard ratio [HR], 0.37;
      carfilzomib, Rd: HR, 0.54; elotuzumab, Rd: HR, 0.54; ixazomib, Rd: HR, 0.50).
      Similar trends were observed for overall survival and overall response. DRd
      showed the greatest probability of being the best treatment for all clinical
      efficacy outcomes. The subgroup analyses results were consistent with the base
      case results. CONCLUSION: In patients with RRMM who are suitable for an IMiD
      containing regimen, DRd showed clear advantages in survival and response outcomes
      compared with other IMiD-containing regimens.

PMID- 29456036
TI  - Diagnostic criteria for acute food protein-induced enterocolitis syndrome. Is the
      work in progress?
AB  - Food protein-induced enterocolitis syndrome (FPIES) is a non IgE-mediated
      gastrointestinal food allergic disorder. Some diagnostic criteria have been
      published for acute FPIES. Of course, they are not all the same, so the clinician
      must choose which ones to adopt for his/her clinical practice. We present here a
      brief review of these criteria and, through two clinical cases, show how the
      choice of one or the other can change the diagnostic destiny of a child with
      suspect FPIES.

PMID- 29456037
TI  - Evaluation of an intervention to improve the management of allergens in school
      food services in the city of Barcelona.
AB  - BACKGROUND: An intervention to promote the development of an allergen control
      plan (ACP) and preventive measures for the management of allergens in school food
      services was implemented in all schools of Barcelona city over a three-year
      period (2013-2015) by the public health services. The present study aimed to
      assess changes regarding the management of food allergens in school food services
      in Barcelona after an intervention conducted by the public health services of the
      city. METHODS: School meal operators of a random sample of 117 schools were
      assessed before and after the intervention using a structured questionnaire. The
      questionnaire collected general information on the students and their demand for
      special menus, and included 17 closed questions regarding the implementation of
      specific preventive measures for the management of allergens. Based on these 17
      questions, a food safety score was calculated for each school. The improvement in
      these scores was evaluated. RESULTS: The results showed positive increments in
      the percentage of implementation of 12 of the 17 preventive measures assessed.
      The percentage of school food services with an implemented ACP increased by 49%.
      Schools with external and internal food supplies increased their scores by 16.5%
      and 19.6%, respectively. The greatest improvements were observed in smaller food
      services and in schools located in districts with low gross household incomes.
      CONCLUSIONS: The intervention was effective in improving school food services'
      management of allergens and in reducing the differences found among food services
      in the pre-intervention survey. We must also focus efforts on reducing socio
      economic inequalities linked to the management of allergens.

PMID- 29456038
TI  - Increase of natural killer cells in children with liver transplantation-acquired
      food allergy.
AB  - BACKGROUND: Transplantation-acquired food allergies (TAFA) are frequently
      reported and considered to be caused by immunosuppressive therapy. The aim of
      this study was to investigate the allergic and immunologic responses in children
      who had liver or kidney transplantations. METHODS: Twelve children receiving
      liver transplantations and 10 children receiving kidney transplantations were
      investigated. All children underwent the allergy work-up and in most of them,
      lymphocyte screening and serum cytokine measurements were also performed.
      RESULTS: TAFA were found in 7/12 (58%) children with liver transplantations and
      in none of the 10 children with kidney transplantations. The mean age at
      transplantation was significantly lower in children who underwent liver
      transplantations (p<0.001). The immunosuppressive therapy administered to
      children with liver transplantation was tacrolimus in 11 patients and
      cyclosporine in one patient, while all 10 children with kidney transplantation
      received tacrolimus plus mycophenolate. The most common antigenic food was egg.
      The natural killer (NK) cell numbers were significantly higher in liver
      transplant children than in kidney-transplant children. No significant
      differences were found in the serum cytokine levels. CONCLUSIONS: This study
      confirms that liver-transplant children treated with tacrolimus alone have a
      higher risk of developing TAFA than kidney-transplant children treated with
      tacrolimus plus mycophenolate. NK cells might be involved in this difference.

PMID- 29456039
TI  - Exposure to dogs but not cats is associated to a decrease in the prevalence in
      atopic dermatitis amongst school-children.
AB  - INTRODUCTION: The association regarding the exposure to pets, especially cats and
      dogs, and the prevalence of allergic diseases is inconsistent. OBJECTIVE: We
      analyzed the role played by early exposure to dogs or cats in the prevalence of
      allergic diseases amongst school-aged children. METHOD: Through a cross-sectional
      study, we examined 756 children, aged 6-7; these candidates were selected through
      cluster sampling. We inquired about the exposure that these children had had to
      dogs and cats, and whether these pets spent most of their time indoors or
      outdoors during the first year of the child's life. In order to identify the
      prevalence of allergic diseases and their symptoms, each child's parent completed
      the International Study of Asthma and Allergies in Childhood questionnaire.
      RESULTS: Exposure to outdoor dogs was associated to nocturnal coughing, odds
      ratio (OR) 0.64, with a confidence interval of 95% (95% CI) 0.43-0.95 and with
      atopic dermatitis (OR: 0.39; 95% CI: 0.20-0.76). Interestingly, exposure to
      outdoor cats was associated to nocturnal coughing (OR: 0.51; 95% CI: 0.32-0.83)
      and current rhinitis symptoms (OR: 0.59; 95% CI 0.36-0.97). After carrying out
      the multivariate analyses, only exposure to dogs, both indoor and outdoor, was
      significantly associated to a decrease in the prevalence of atopic dermatitis OR
      0.40 (95% CI: 0.20-0.79) and OR 0.38 (95% CI: 0.18-0.83), respectively.
      CONCLUSION: Our findings suggest that exposure to dogs, whether they be indoor or
      outdoor pets, is associated to a decreased prevalence in atopic dermatitis.

PMID- 29456040
TI  - A very rare case of renal cell carcinoma metastasis to spermatic cord and a
      condensed literature review.
AB  - INTRODUCTION: Renal cell carcinoma (RCC) is proved to be the ninth most common
      malignancy. Two-third of the patients suffering from RCC will present metastases.
      Secondary metastases of RCC to spermatic cord are very rare. PRESENTATION OF
      CASE: In this report we present the case of a patient with renal cell carcinoma
      with metachronous metastasis to the spermatic cord occurring two years after the
      initial diagnosis of the disease. DISCUSSION: Our patient was treated according
      to EAU guidelines. The metastatic tumor was diagnosed accidentally, in contrast
      to the previous follow-up exams which show no disease in the meantime. Moreover,
      the histological examination of the spermartic cord tumor illustrated tumor
      thrombus. The former examination results along with the anatomical and
      embryological relations of renal and spermatic cord structures indicate a
      hypothesis about the mechanism of this metastasis' route. CONCLUSION: Our case is
      of great interest, since such cases are very few in the international literature.
      Therefore the presentation of this case as well as its implications should be
      made to the global surgery community.

PMID- 29456041
TI  - Translational Research - Intervention Strategies for Improving Pediatric Nursing
      Practice to Promote the Health of Children and Adolescents.

PMID- 29456042
TI  - Evidence to improve the treatment of infections caused by carbapenem-resistant
      Gram-negative bacteria.

PMID- 29456044
TI  - Mesoporous silica nanoparticles functionalized with hyaluronic acid. Effect of
      the biopolymer chain length on cell internalization.
AB  - Mesoporous silica nanoparticles (MSNs) were functionalized with amino groups (MSN
      NH2) and then with hyaluronic acid, a biocompatible biopolymer which can be
      recognized by CD44 receptors in tumor cells, to obtain a targeting drug delivery
      system. To this purpose, three hyaluronic acid samples differing for the
      molecular weight, namely HAS (8-15 kDa), HAM (30-50 kDa) and HAL (90-130 kDa),
      were used. The MSN-HAS, MSN-HAM, and MSN-HAL materials were characterized through
      zeta potential and dynamic light scattering measurements at pH = 7.4 and T = 37 
      degrees C to simulate physiological conditions. While zeta potential showed an
      increasing negative value with the increase of the HA chain length, an anomalous
      value of the hydrodynamic diameter was observed for MSN-HAL, which was smaller
      than that of MSN-HAS and MSN-HAM samples. The cellular uptake of MSN-HA samples
      on HeLa cells at 37  degrees C was studied by optical and electron microscopy. HA
      chain length affected significantly the cellular uptake that occurred at a higher
      extent for MSN-NH2 and MSN-HAS than for MSN-HAM and MSN-HAL samples. Cellular
      uptake experiments carried out at 4  degrees C showed that the internalization
      process was inhibited for MSN-HA samples but not for MSN-NH2. This suggests the
      occurrence of two different mechanisms of internalization. For MSN-NH2 the uptake
      is mainly driven by the attractive electrostatic interaction with membrane
      phospholipids, while MSN-HA internalization involves CD44 receptors overexpressed
      in HeLa cells.

PMID- 29456043
TI  - Colistin alone versus colistin plus meropenem for treatment of severe infections
      caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised
      controlled trial.
AB  - BACKGROUND: Colistin-carbapenem combinations are synergistic in vitro against
      carbapenem-resistant Gram-negative bacteria. We aimed to test whether combination
      therapy improves clinical outcomes for adults with infections caused by
      carbapenem-resistant or carbapenemase-producing Gram-negative bacteria. METHODS:
      A randomised controlled superiority trial was done in six hospitals in Israel,
      Greece, and Italy. We included adults with bacteraemia, ventilator-associated
      pneumonia, hospital-acquired pneumonia, or urosepsis caused by carbapenem-non
      susceptible Gram-negative bacteria. Patients were randomly assigned (1:1)
      centrally, by computer-generated permuted blocks stratified by centre, to
      intravenous colistin (9-million unit loading dose, followed by 4.5 million units
      twice per day) or colistin with meropenem (2-g prolonged infusion three times per
      day). The trial was open-label, with blinded outcome assessment. Treatment
      success was defined as survival, haemodynamic stability, improved or stable
      Sequential Organ Failure Assessment score, stable or improved ratio of partial
      pressure of arterial oxygen to fraction of expired oxygen for patients with
      pneumonia, and microbiological cure for patients with bacteraemia. The primary
      outcome was clinical failure, defined as not meeting all success criteria by
      intention-to-treat analysis, at 14 days after randomisation. This trial is
      registered at ClinicalTrials.gov, number NCT01732250, and is closed to accrual.
      FINDINGS: Between Oct 1, 2013, and Dec 31, 2016, we randomly assigned 406
      patients to the two treatment groups. Most patients had pneumonia or bacteraemia
      (355/406, 87%), and most infections were caused by Acinetobacter baumannii
      (312/406, 77%). No significant difference between colistin monotherapy (156/198,
      79%) and combination therapy (152/208, 73%) was observed for clinical failure at
      14 days after randomisation (risk difference -5.7%, 95% CI -13.9 to 2.4; risk
      ratio [RR] 0.93, 95% CI 0.83-1.03). Results were similar among patients with A
      baumannii infections (RR 0.97, 95% CI 0.87-1.09). Combination therapy increased
      the incidence of diarrhoea (56 [27%] vs 32 [16%] patients) and decreased the
      incidence of mild renal failure (37 [30%] of 124 vs 25 [20%] of 125 patients at
      risk of or with kidney injury). INTERPRETATION: Combination therapy was not
      superior to monotherapy. The addition of meropenem to colistin did not improve
      clinical failure in severe A baumannii infections. The trial was unpowered to
      specifically address other bacteria. FUNDING: EU AIDA grant Health-F3-2011
      278348.

PMID- 29456045
TI  - Hepatectomy for octogenarians with colorectal liver metastasis in the era of
      enhanced recovery.
AB  - BACKGROUND: Concern exists regarding the use of hepatectomy to treat colorectal
      liver metastasis (CRLM) in octogenarians due to prior studies suggesting elevated
      morbidity and mortality. Cardiopulmonary exercise testing (CPET) within pre
      operative assessment and enhanced recovery after surgery (ERAS) have both been
      shown to be associated with low morbidity and mortality in patients undergoing
      hepatectomy. This study sought to compare the outcomes of octogenarians with
      patients aged 70-79 undergoing hepatectomy for CRLM, within a center utilizing
      both CPET and ERAS. METHODS: Consecutive patients age 70 or older who underwent
      hepatectomy for CRLM at Aintree University Hospital (Liverpool,UK), between May
      2008 and May 2015 were identified from a prospectively maintained cancer
      database. Data were extracted and comparisons drawn. RESULTS: 127 patients aged
      70-79 years and 34 octogenarians underwent respectively 137 and 35 hepatectomy
      for CRLM. There was no difference in hospital stay (6 days), morbidity and
      mortality between the groups. OS at 1, 3 and 5 years were 86.7%, 55% and 35.8%
      for those aged 70-79 compared to 79.4%, 37.3% and 20.4% for the octogenarians
      (p=0.127). DFS at 1,3 and 5 years was 52.5%, 31.7% and 31.7% for 70-79 group
      compared to 46.2%, 31.5% and 16.8% for the octogenarians (p=0.838). On
      multivariate analysis major hepatectomy was associated with an increased risk of
      post-operative complications, inferior OS and DFS. Chronological age was not a
      predictor of postoperative complications, poorer OS or DFS. CONCLUSIONS:
      Appropriately selected octogenarians can have similar postoperative outcomes to
      patients aged 70-79 when undergoing hepatectomy for CRLM using ERAS combined with
      CPET. This study advocates using CPET and ERAS in the selection and management of
      octogenarian patients with CRLM undergoing hepatectomy.

PMID- 29456046
TI  - The spectrum of "off" in Parkinson's disease: What have we learned over 40 years?
AB  - The terms "on" and "off" were used by Marsden and his contemporaries over 40
      years ago to describe times when Parkinson's disease patients experienced good
      motor function ("on") and immobility ("off"). Yet there remains no published
      consensus definition of "off", leading clinicians and patients to develop
      individualized impressions of "off" determinations. In this paper, we first
      discuss the evolution of the terminology and understanding of "off" states since
      Marsden's time, which now include non-motor as well as motor symptoms. We then
      review pathophysiology and risk factors for the development of "off" states as
      well as tools to detect the "off" state, before proposing a practical definition
      of "off" for consideration. A common, practical definition of the "off" state
      could improve clinical recognition of "off" symptoms and lead to significant
      benefit for patients.

PMID- 29456047
TI  - Catheter Versus Surgical Ablation of Atrial Fibrillation: An Analysis of
      Outcomes.

PMID- 29456048
TI  - Gluteal Leiomyosarcoma: A Rare Cause of Severe Mitral Stenosis.

PMID- 29456049
TI  - Six-Month Outcomes After High-Risk Coronary Artery Bypass Graft Surgery and
      Preoperative Intra-aortic Balloon Counterpulsation Use: An Inception Cohort
      Study.
AB  - OBJECTIVE: To inform the design of a pivotal randomized controlled trial of
      prophylactic intra-aortic balloon counterpulsation (IABC) in patients undergoing
      coronary artery bypass graft (CABG) at high risk of postoperative low cardiac
      output syndrome (LCOS). DESIGN: Inception cohort study. SETTING: A total of 13
      established cardiac centers in Australia, Canada, New Zealand, and the United
      Kingdom. PARTICIPANTS: Adult patients were eligible for inclusion if they were
      listed for CABG surgery and had 2 or more LCOS risk factors (low ejection
      fraction, severe left main coronary artery disease, redo sternotomy, unstable
      angina). INTERVENTIONS: Outcomes of interest were a composite outcome of in
      hospital mortality, postoperative acute myocardial infarction (AMI), acute kidney
      injury (AKI), or stroke as well as 6-month vital status and quality of life using
      the EuroQol 5-dimensional questionnaire (EQ5D). MEASUREMENTS AND MAIN RESULTS:
      The study included 136 participants over a 29-month period. Overall, in-hospital
      and 6-month mortality occurred in 7 (5%) and 11 (8%) participants, respectively.
      The composite outcome occurred in 60 (44%). The mean increase in EQ5D summary
      index at 6 months was 0.10 (standard deviation 0.24, p = 0.01). Perioperative
      AMI, AKI, or stroke significantly decreased the odds of a clinically meaningful
      improvement in quality of life (odds ratio 0.32; 95% confidence interval 0.13
      0.79; p = 0.014). Preoperative IABC was used in 39 participants and did not
      predict postoperative outcomes. CONCLUSIONS: The study identified a group of
      patients at risk of LCOS in whom CABG surgery was associated with a substantial
      burden of perioperative morbidity. Preoperative IABC use was variable, supporting
      the need for further research.

PMID- 29456050
TI  - Blood Transfusions in Cardiac Surgery: Balancing Science and Art.

PMID- 29456051
TI  - Computerization of health warnings and incident reports for Materials Vigilance
      in the Marseille Public Hospitals.

PMID- 29456052
TI  - Performance of a highly successful outbreak strain of Mycobacterium tuberculosis
      in a multifaceted approach to bacterial fitness assessment.
AB  - Determining bacterial fitness represents a major challenge and no single
      parameter can accurately predict the ability of a certain pathogen to succeed.
      The M strain of Mycobacterium tuberculosis managed to spread and establish in the
      community and caused the largest multidrug-resistant tuberculosis outbreak in
      Latin America. We have previously shown that the M strain can manipulate the host
      immune response, but we still have no direct evidence, other than epidemiology,
      that can account for the enhanced fitness of the M strain. Our objective was to
      further characterize the performance of the outbreak strain M in different
      fitness assays. Two main aspects were evaluated: (1) molecular characterization
      of selected isolates from the M outbreak and related strains and (2) comparative
      fitness and in vivo performance of representative M strain isolates vs. the non
      prosperous M strain variant 410. Our approach confirmed the multifaceted nature
      of fitness. Altogether, we conclude that the epidemiologically abortive strain
      410 was vulnerable to drug-driven pressure, a weak competitor, and a stronger
      inductor of protective response in vivo. Conversely, the isolate 6548,
      representative of the M outbreak peak, had a growth disadvantage but performed
      very well in competition and induced lung damage at advanced stages in spite of
      reaching relatively low CFU counts. Integration of these observations supports
      the idea that the M strain managed to find a unique path to success.

PMID- 29456053
TI  - Conjoint Analysis of Treatment Preferences for Nondisplaced Scaphoid Fractures.
AB  - PURPOSE: We used conjoint analysis to assess the relative importance of factors
      that influence a patient's decision between surgical or nonsurgical management of
      a nondisplaced scaphoid fracture. Our hypothesis was that out-of-pocket costs
      will have a greater influence on decision making than the time spent in a cast or
      brace, degree of soreness, or the risk of treatment failure. METHODS: Two-hundred
      and fifty participants were recruited using Amazon Mechanical Turk and asked to
      assume that they had experienced a nondisplaced scaphoid waist fracture. They
      then indicated their relative preferences among 13 pairs of alternatives with
      variations in the following attributes: time in a cast, time in a brace, duration
      of ongoing soreness, risk of treatment failure (by which we meant scaphoid
      nonunion), out-of-pocket costs based on estimates of direct costs ($500-2,500),
      and apprehension about surgery. A conjoint analysis was used to determine the
      relative importance of these factors when choosing between surgical or
      nonsurgical management. RESULTS: The factor with the greatest influence on
      treatment choice was the cost of the procedure. After assessing the respondent's
      apprehension to undergo surgery, a sensitivity analysis showed the proportion of
      respondents who would choose surgery given different outcomes. To make the
      predicted share of those who are "not worried" about surgery equal to those who
      are "somewhat worried" or "a little worried" would require that the cost of
      surgery increase by $2,700. In addition, 2 weeks in a cast, 3 weeks in a brace, 2
      months of soreness, or a 2% increase in the risk of fracture nonunion generates
      the same surgical choice probability as a $2,000 increase in the out-of-pocket
      cost of surgery. CONCLUSIONS: As conceptualized in this conjoint analysis, out-of
      pocket costs and apprehension about surgery seem to have a greater impact on a
      decision for surgery than the time spent in a brace or cast and the risk of
      treatment failure. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic and decision
      analysis III.

PMID- 29456055
TI  - RE: "Antibiotic treatment of asymptomatic bacteriuria prior to hip and knee
      arthroplasty: A systematic review of the literature" by Mayne et al.

PMID- 29456054
TI  - The Relationship Between Serum Interleukin-1alpha and Asymptomatic Infrarenal
      Abdominal Aortic Aneurysm Size, Morphology, and Growth Rates.
AB  - OBJECTIVE/BACKGROUND: In a pilot study, a relationship between abdominal aortic
      aneurysm (AAA) diameter and serum interleukin (IL)-1alpha levels was reported,
      and that endothelial cell (EC) activation in vitro in response to serum from
      patients with AAA was blocked by anti-IL-1alpha antibodies. The aim of the
      present study was to further investigate the relationship between serum IL-1alpha
      and asymptomatic infrarenal AAA size, morphology, and growth rates. METHODS:
      Serum IL-1alpha was measured using enzyme linked immunosorbent assay in 101
      patients with asymptomatic, infrarenal AAA and related to aneurysm size,
      morphology, and growth rates. RESULTS: IL-1alpha was measured in 101 patients.
      There was no statistically significant difference in mean age between men and
      women. IL-1alpha was detectable in 62.4% of patients; median IL-1alpha titre was
      3.26 pg/mL. There was no statistically significant relationship between IL-1alpha
      and maximum AAA antero-posterior diameter as measured by ultrasound (p = .649),
      AAA morphology (aortic length [p = .394], sac [p = .369], and thrombus volume [p
      = .629]) as measured on computed tomography, absolute increase in AAA diameter (p
      = .214), or AAA growth rate (p = .230). CONCLUSION: IL-1alpha is detectable in
      the majority of patients with infrarenal AAA, but the cause and clinical
      significance of this novel observation remains unknown.

PMID- 29456056
TI  - A preliminary exploration of plain-film radiography in scapular dyskinesis
      evaluation.
AB  - BACKGROUND: Evaluation of scapular dyskinesis is of clinical interest because it
      is believed to be associated with pathologies of the shoulder. This study
      investigated the feasibility of plain-film radiography in evaluating scapular
      dyskinesis. METHODS: Subjects with unilateral disorders of the shoulder (n = 186)
      who underwent plain-film radiography of bilateral scapulae were divided into 4
      categories of scapular dyskinesis patterns according to the Kibler classification
      and analyzed. Coracoid upward shift distance (CUSD), length of the scapular spine
      line (LSS), and scapular upward rotation angle (SURA) were measured on the
      radiographs. Intrarater and inter-rater reliability were tested, and the
      characteristics of these parameters in each type were analyzed. The differences
      (d) between bilateral scapulae (d-CUSD, d-LSS, and d-SURA) among the 4 categories
      were compared. RESULTS: Intrarater and inter-rater reliability were excellent for
      all parameters. Significant differences between the scapulae were observed in
      CUSD in type I and in LSS in type II categories. No significant difference in any
      of the parameters was found in type III. Compared with the other categories, d
      CUSD in type I and d-LSS in type II were significantly larger. The cutoff values
      of d-CUSD and d-LSS were 1.1 mm and 1.2 mm, respectively. No significant
      difference in d-SURA was found among the 4 categories. CONCLUSIONS: The
      measurement of CUSD, LSS, and SURA on plain-film radiography had excellent
      reliability. d-CUSD and d-LSS were characteristic parameters of type I and type
      II, respectively; however, type III had no distinguishing characteristics among
      the parameters.

PMID- 29456057
TI  - Significance of macro creatine kinase in admitted patients.

PMID- 29456058
TI  - Comparison of the 9-month intra-stent conditions and 2-year clinical outcomes
      after Resolute zotarolimus-eluting stent implantation between 3-month and
      standard dual antiplatelet therapy.
AB  - BACKGROUND: The use of short-duration dual antiplatelet therapy (DAPT) remains
      controversial. To investigate efficacy and safety of short-duration DAPT, we
      performed a detailed comparison of intra-stent conditions by optical coherence
      tomography (OCT) after second-generation drug-eluting stent implantation with
      short-term and standard DAPT. METHODS AND RESULTS: Eighty-two consecutive
      patients with stable angina pectoris who received Resolute zotarolimus-eluting
      stents (R-ZESs; Medtronic Cardiovascular, Santa Rosa, CA, USA) were enrolled.
      Patients were assigned to 3-month (3M group: 41 patients) and standard (standard
      group: 41 patients) DAPT. In the 3M group, clopidogrel was discontinued 3 months
      after stent implantation. In the standard group, DAPT was maintained until follow
      up OCT. At 9 months, neointimal proliferation was significantly larger in the 3M
      group, but there were no significant between-group differences in the proportion
      of uncovered and malapposed strut. The prevalence of abnormal intra-stent tissue
      (AIT) at 9 months was equivalent between groups. A multiple regression analysis
      revealed malapposition at 9 months as the strongest independent predictor of AIT
      at 9 months, and the prevalence of AIT was not associated with DAPT duration.
      Over 2 years, cardiac events were equal between groups; however, major bleeding
      was higher tendency in the standard group than in the 3M group. CONCLUSION: This
      OCT study indicated that reducing DAPT's duration may provide acceptable arterial
      healing in patients with implanted R-ZESs.

PMID- 29456059
TI  - Chronic Central Venous Access: From Research Consensus Panel to National
      Multistakeholder Initiative.

PMID- 29456060
TI  - Association of TNF-alpha but not IL-1beta levels with the presence of
      Helicobacter pylori infection increased the risk of peptic ulcer development.
AB  - Peptic ulcer is a lesion in the mucosa of the digestive tract affecting many
      people all around the world. Recent investigations have indicated that produced
      inflammatory cytokines such as TNF-alpha and IL-1beta in response to gastric
      infection by Helicobacter pylori play an important role in the development of
      peptic ulcer. With regard to the significance of these cytokines in peptic ulcer
      development and the high prevalence of this disease in the developing countries,
      this study aimed to investigate the association of TNF-alpha and IL-1beta with
      peptic ulcer in the presence of H. pylori. This case-control study enrolled 61
      patients with peptic ulcer disease (PUD) as cases and 59 people without peptic
      ulcer (NPUD) as controls. Blood samples and endoscopic biopsies were collected.
      H. pylori infection was confirmed by using rapid urease test (RUT), specific IgG
      measurement and histopathological examination. Then, IL-1beta and TNF-alpha
      levels were evaluated using enzyme linked immunosorbent assay (ELISA). The
      seropositivity of H. pylori was 62.5% in the studied population, while by
      considering RUT and histopathological examination along with specific-IgG
      antibody, H. pylori infection decreased to 56.7%. In addition, H. pylori
      infection was significantly (OR = 0.37; 95% CI = 0.17-0.82; P = .02) associated
      with peptic ulcer development. The TNF-alpha level in PUD and infected H. pylori
      subjects was significantly higher than that of control and un-infected H. pylori
      individuals. However, no significant difference of IL1beta level was observed
      between PUD and control groups as well as between H. pylori infected and un
      infected individuals. Interestingly, IL-1beta level in PUD patients without H.
      pylori infection was significantly higher than infected ones. Moreover, a
      significant correlation between specific-IgG antibody with TNF-alpha level was
      observed. Taken together, our results showed that increased level of TNF-alpha
      could probably play pivotal role in pathogenesis of peptic ulcer in the presence
      of H. pylori infection. These findings also highlighted the importance of IL
      1beta in the absence of H. pylori infection in peptic ulcer development.

PMID- 29456061
TI  - The Drosophila cytokine, GBP: A model that illuminates the yin-yang of
      inflammation and longevity in humans?
AB  - Our laboratories have determined that the Drosophila cytokine, Growth-blocking
      peptide (GBP), mediates its biological effects through the Mthl10 G-protein
      coupled receptor. In this Cytokine Stimulus, we discuss the functional plasticity
      of the GBP/Mthl10 axis, and we propose that conserved components of this
      regulatory network may be relevant to human health.

PMID- 29456062
TI  - Value of double pedicled mucoperiosteal flaps for the prevention of restenosis in
      Draf IIb frontal sinusotomy.
AB  - INTRODUCTION: The extent of bone exposure is one of the major factors
      contributing to failure of endoscopic frontal sinusotomy procedures. Double flaps
      providing cover of exposed bone have already been described for Draf III
      procedures in a cadavre study using posterior and lateral pedicled nasoseptal
      flaps. As these flaps overlap on the septal side, they cannot be raised from the
      same nasal cavity in a Draf IIb procedure. We describe a new technique using 2
      local mucoperiosteal flaps raised from the same side to entirely cover the bone
      margins exposed by Draf IIb frontal sinusotomy. SURGICAL TECHNIQUE: A left Draf
      IIb procedure was performed to drain a frontal mucocele. A posterior
      septoturbinal flap (PSTF) was raised to cover the posterior sinusotomy margin. A
      lateral pedicle nasoseptal flap (LNSF) was raised on the same side to cover the
      anterior margin. With a follow-up of 6 months, the Draf IIb cavity was fully
      patent and the flaps were well integrated. CONCLUSION: PSTF and LNSF flaps can be
      raised on the same side to cover the posterior and anterior margins of the Draf
      IIb frontal sinusotomy, respectively.

PMID- 29456063
TI  - Clinical Outcome of Arthroscopic Lateral Retinacular Release for Symptomatic
      Bipartite Patella in Athletes.
AB  - PURPOSE: To report the results of arthroscopic lateral retinacular release
      without excision of the accessory fragment for treatment of symptomatic bipartite
      patella with a minimum 2-year follow-up. METHODS: We retrospectively reviewed all
      cases of symptomatic type III bipartite patella confirmed by radiographs,
      computed tomography, and magnetic resonance imaging and treated with arthroscopic
      lateral release from 2005 to 2015. Patients with history of knee fractures or
      surgery, concomitant meniscal or anterior cruciate ligament (ACL) procedures, and
      severe arthritic changes of the patellofemoral joint were excluded. Patients were
      assessed by Kujala score, visual analog scale (VAS), Tegner Activity Scale (TAS),
      and time to return to sporting activities. RESULTS: Ten patients (11 knees) were
      clinically reassessed after 69.6 +/- 33.3 (range: 25-132; 95% confidence interval
      [CI]: 47.29-91.99) months from surgery. There was a significant improvement in
      Kujala (P < .05) and VAS scores (P < .05), and no differences were found between
      pre- and postoperative TAS scores (P > .05). No complications occurred during the
      follow-up period. All patients returned to sport after 42.3 +/- 11.3 (range: 30
      60; 95% CI: 34.71-49.84) days after surgery. CONCLUSIONS: The arthroscopic
      lateral retinacular release of a symptomatic type III bipartite patella without
      excision of the accessory fragment allowed early return to sporting activities,
      with excellent symptom relief. Patients had significantly improved mean Kujala
      and VAS scores without a decrease in the mean TAS scores. LEVEL OF EVIDENCE:
      Level IV, case series.

PMID- 29456064
TI  - Triple-Loaded Suture Anchors Versus a Knotless Rip Stop Construct in a Single-Row
      Rotator Cuff Repair Model.
AB  - PURPOSE: To compare the biomechanical properties of single-row repair with triple
      loaded (TL) anchor repair versus a knotless rip stop (KRS) repair in a rotator
      cuff repair model. METHODS: Rotator cuff tears were created in 8 cadaveric
      matched-pair specimens and repaired with a TL anchor or KRS construct. In the TL
      construct, anchors were placed in the greater tuberosity and then all suture
      limbs were passed through the rotator cuff as simple sutures and tied. In the KRS
      construct, a 2-mm suture tape was passed through the tendon in an inverted
      mattress fashion, and a free suture was passed medial to the suture tape to
      create a rip-stop. Then, the suture tape and free suture were secured with
      knotless anchors. Displacement was observed with video tracking after cyclic
      loading, and specimens were loaded to failure. RESULTS: The mean load to failure
      was 438 +/- 59 N in TL anchor repairs compared with 457 +/- 110 N in KRS repairs
      (P = .582). The mean displacement with cyclic loading was 3.8 +/- 1.6 mm in TL
      anchor repairs versus 4.3 +/- 1.8 mm in the KRS group (P = .297). Mode of failure
      was consistent in both groups, with 6 of 8 failures in the TL anchor group and 7
      of 8 failures in KRS group occurring from anchor pullout. CONCLUSIONS: There is
      no statistical difference in load to failure and cyclic loading between TL anchor
      and KRS single-row repair techniques. CLINICAL RELEVANCE: KRS repair technique
      may be an alternative method of repairing full-thickness supraspinatus tendon
      tears with a single-row construct.

PMID- 29456065
TI  - Endoscopy-Assisted Hallux Valgus Correction Provides Sustainable Long-Term >10
      Year Outcomes.
AB  - PURPOSE: This study aims to review the long-term efficacy of the endoscopy
      assisted distal soft-tissue procedure (EDSTP) and to see whether operative
      correction can be maintained for >10 years. METHODS: All hallux valgus cases
      undergoing EDSTP from 2000 to 2006 were recruited. Preoperative, postoperative,
      and 10-year follow-up x-rays were analyzed. A pain score from the preoperative
      and >10-year follow-up was recorded. The American Orthopaedic Foot and Ankle
      Society (AOFAS) hallux score and Foot and Ankle Outcome Score (FAOS) were
      measured at the >10-year follow-up. RESULTS: A total of 85 cases met the
      inclusion criteria with an EDSTP performed between January 2000 and December 2006
      and had a follow-up of >10 years. Hallux valgus angle corrected from 25.8 degrees
      to 11.2 degrees  (P < .001), 1,2 intermetatarsal angle (1,2 IMA) improved from
      13.5 degrees  to 9.5 degrees  (P < .001), and the tibial sesamoid position
      changed from 4 to 1 (P < .001). Pain improved from preoperative 6.5/10 to 0.5/10
      (P < .001). AOFAS score was 93.5/100 at >10-year follow-up, and the FAOS was good
      in all 5 subcategories (range, 72.6-89.3). CONCLUSIONS: Our results show that the
      EDSTP has good early postoperative results that are maintained for >10 years. It
      provides good long-term radiological correction, in addition to lasting pain
      relief and great foot function, using only 5 incisions. LEVEL OF EVIDENCE: Level
      IV, case series.

PMID- 29456066
TI  - Slight Reduction in the Insertion Depth for an All-Suture Anchor Decreases Cyclic
      Displacement in the Shoulder Glenoid.
AB  - PURPOSE: To determine if the depth of anchor insertion affects the biomechanical
      performance of a 1.5-mm all-suture anchor in glenoid bone. METHODS: A 1.5-mm all
      suture anchor was tested in 8 matched pairs of human cadaver fresh-frozen
      glenoids. Anchors were inserted at 6 different locations and tested at 3
      different depths: 21 mm (preset drilling depth), 17 mm, and 13 mm. Cyclic loading
      and destructive testing was performed. Displacement after 100 and 200 cycles,
      along with ultimate failure strength, was determined. RESULTS: After 100 and 200
      cycles, anchors placed at 13 and 17 mm had undergone significantly less
      displacement than those at 21 mm (P < .05). No difference was observed in
      ultimate load to failure between anchors placed at 21 and 17 mm. However, the
      ultimate load to failure was significantly lower in anchors placed at 13 mm (P <
      .05). There were 5 clinical failures in anchors placed at 21 mm, one at 17 mm,
      and none at 13 mm. CONCLUSIONS: The 1.5-mm all-suture anchor tested in this study
      has an optimal insertion depth of 17 mm, 4 mm shallower than the preset drill
      depth. At the optimal insertion depth of 17 mm, it underwent significantly less
      displacement after cyclic loading without a reduction in the ultimate load to
      failure. CLINICAL RELEVANCE: Given the results of this study, the optimal
      insertion depth for this 1.5-mm all-suture anchor is 17 mm, 4 mm shallower than
      the preset drill depth.

PMID- 29456067
TI  - Revision Hip Arthroscopy After Labral Reconstruction Using Iliotibial Band
      Autograft: Surgical Findings and Comparison of Outcomes With Labral
      Reconstructions Not Requiring Revision.
AB  - PURPOSE: To determine the causes of revision hip arthroscopy in patients who
      underwent labral reconstruction and to compare outcomes of these patients with
      patients who did not require a revision following reconstruction. METHODS:
      Patients who underwent revision hip arthroscopy after previous labral
      reconstruction from 2006 to 2014 were included. Patients with less than 2-year
      follow-up, preoperative joint space of <=2 mm, or who underwent other
      reconstructive procedures at the time of labral reconstruction were excluded.
      Each patient was matched by year of surgery, age, gender, and the number of
      previous surgeries with 2 patients that underwent labral reconstruction but did
      not require a revision following the reconstruction. Preoperatively and at a
      minimum 2-year follow-up, outcome scores were collected including the Hip Outcome
      Score-Activities of Daily Living (HOS-ADL) and HOS-Sports Scale, modified Harris
      Hip Score, Western Ontario and McMaster Universities Index (WOMAC), the 12-Item
      Short Form Health Survey (SF-12) Physical Component Summary, and the patient
      satisfaction outcome were collected. Differences between the preoperative and the
      postoperative outcomes score of each patient in the 2 groups was assessed using
      the paired t test. The Mann-Whitney U test was used to compare the 2 groups.
      RESULTS: From 347 patients who underwent iliotibial band autograft labrum
      reconstruction from 2006 to 2014, 28 hips (8%) in 26 patients (18 females and 8
      males) had revision arthroscopy after labral reconstruction. The mean age was 32
      years (range: 16-64). The mean number of hip surgeries prior to the labral
      reconstruction was 1.9 +/- 1.2. The average time from the last labral
      reconstruction procedure to revision labral reconstruction was 27 months (range:
      5-59). Procedures performed at revision included lysis of adhesions (100%),
      additional femoroacetabular impingement (FAI) correction (50%), ligamentum teres
      debridement (50%), psoas release (29%), labral augmentation or reconstruction
      (14%), and others. Following revision surgery after previous labral
      reconstruction, 4 patients (14%) underwent total hip arthroplasty and 2 (7%)
      patients required a subsequent revision arthroscopy (age 67 and 23) at 15 months
      and 16 months. The average follow-up time was 3.6 years +/- 1 year after revision
      following labral reconstruction and after labral reconstruction in the
      nonrevision group. No significant difference was detected in the outcome scores
      and postoperative satisfaction between the 2 groups. The HOS-ADL improved 16
      points in the nonrevision group and 19 points in the revision group. CONCLUSIONS:
      Patients who underwent revision surgery after labral reconstruction were mostly
      female, with 2 or more surgeries prior to reconstruction, and 14% required THA
      and 7% had recurrent scarring. In those who did not fail, outcomes significantly
      improved and were similar with patients who did not need revision. Adhesions and
      residual FAI were the most common findings during revision labral reconstruction.
      LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 29456068
TI  - Magnetic Resonance Imaging Diagnosis of Medial Meniscal Ramp Lesions in Patients
      With Anterior Cruciate Ligament Injuries.
AB  - PURPOSE: To prospectively evaluate the sensitivity and specificity of magnetic
      resonance imaging (MRI) for diagnosing ramp lesions, to compare them between 1.5-
      and 3-T MRI, and to evaluate whether bone contusion of the posterior lip of the
      medial tibial plateau was associated with ramp lesions. METHODS: For 155 knees
      that underwent primary ACL reconstruction, we prospectively examined for ramp
      lesions and medial meniscal body tears on MRI. MRI diagnosis of ramp lesions
      required high signal irregularity of the capsular margin or separation in the
      meniscocapsular junction of the medial meniscus posterior horn on sagittal
      images. Bone contusion of the posterior lip of the medial tibial plateau was
      verified in 105 knees with MRI performed within 6 weeks after injury. All ramp
      lesions were identified by transcondylar observation during surgery. The
      sensitivity and specificity of MRI for ramp lesions and body tears were measured.
      Furthermore, we evaluated whether bone contusion of the medial tibial plateau was
      associated with ramp lesions. The chi-square test was used for statistical
      analysis. RESULTS: During surgery, ramp lesions were observed in 46 knees and
      medial meniscal body tears were seen in 35 knees. The sensitivity of MRI for ramp
      lesions was 71.7% and specificity was 90.5%. The sensitivity for ramp lesions was
      significantly lower than that for meniscal body tears (94.3%) (P = .01). The
      sensitivity of 3-T MRI (83.3%) was superior to that of 1.5-T MRI (67.6%), but not
      significantly different. The incidence of bone contusions was not significantly
      different among ramp lesions (38.5%), body tears (40.0%), or no tears (30.5%).
      CONCLUSIONS: The sensitivity of MRI for diagnosing ramp lesions was significantly
      lower than that for medial meniscal body tears. Bone contusion of the posterior
      lip of the medial tibial plateau on MRI was not associated with ramp lesions.
      LEVEL OF EVIDENCE: Level III, comparative trial.

PMID- 29456069
TI  - Arthroscopic Superior Capsular Reconstruction With Acellular Dermal Allograft for
      the Treatment of Massive Irreparable Rotator Cuff Tears: Short-Term Clinical
      Outcomes and the Radiographic Parameter of Superior Capsular Distance.
AB  - PURPOSE: This outcome analysis presents 88 consecutive shoulders presenting with
      irreparable rotator cuff tears that we treated with arthroscopic superior
      capsular reconstruction (SCR) using an acellular dermal allograft. We also
      present the concept of superior capsular distance to quantitatively measure the
      decreased distance present upon restoration of superior capsular integrity.
      METHODS: A retrospective review was conducted of patients treated with
      arthroscopic SCR with a minimum 12-month follow-up. Outcome analysis was
      performed via an internet-based outcome-tracking system to evaluate visual analog
      scale (VAS) and American Shoulder and Elbow Surgeons (ASES) scores. Radiographic
      analysis of anteroposterior radiographs analyzed acromiohumeral interval and
      superior capsular distance. Digital dynamometric strength and functional range of
      motion assessments were also obtained. The main inclusion criteria for patients
      in this analysis was all patients who underwent superior capsular reconstruction
      during the time period of this report. RESULTS: Eighty-six patients with an
      average age of 59.4 years presented with massive rotator cuff tears (Cofield >5
      cm). Outcome data revealed improvement in VAS (4.0-1.5), and ASES (52-82) scores
      at 1 year (P = .005). Radiographic analysis showed increase in acromiohumeral
      interval (mean 7.1 mm preoperatively to mean 9.7 mm at 1 year) (P = .049) and
      superior capsular distance (mean 52.9 mm preoperatively to mean 46.2 mm at 1
      year) (P = .011). Strength improved significantly (forward
      flexion/abduction/external rotation of 4.8/4.1/7.7 lb preoperatively to
      9.8/9.2/12.3 lb at 1 year) as well as range of motion (forward flexion/abduction
      of 120 degrees /103 degrees  preoperatively to 160 degrees /159 degrees  at 1
      year) (P = .044/P = .007/P = .02). At follow-up, 90% of patients were satisfied.
      CONCLUSIONS: This analysis reveals that arthroscopic SCR with acellular dermal
      allograft has been successful in decreasing pain and improving function in this
      patient subset. Radiographic analysis has also shown a consistent and lasting
      decrease in superior capsular distance and increase in acromiohumeral interval,
      indicating maintenance of superior capsular stability. LEVEL OF EVIDENCE: Level
      IV, retrospective case series.

PMID- 29456070
TI  - PCR ribotyping and antimicrobial susceptibility testing of isolates of
      Clostridium difficile cultured from toxin-positive diarrheal stools of patients
      receiving medical care in Canadian hospitals: the Canadian Clostridium difficile
      Surveillance Study (CAN-DIFF) 2013-2015.
AB  - Clostridium difficile toxin-positive diarrheal stool specimens submitted to eight
      Canadian hospital laboratories from 2013 to 2015 were cultured. Polymerase chain
      reaction ribotyping of isolates was performed using an internationally
      standardized, high-resolution capillary gel-based electrophoresis protocol and
      antimicrobial susceptibility testing conducted by CLSI-defined agar dilution (M11
      A8, 2012). Among the 1310 isolates of C. difficile cultured, 141 different
      ribotypes were identified; the most common ribotypes were 027 (24.5% of
      isolates), 014 (7.7%), 020 (6.6%), 106 (6.1%), and 002 (4.6%). Ribotype 027 was
      the commonest ribotype in all geographic regions of Canada and was more
      frequently isolated from patients aged >=80 years (40.6%) than younger patients
      (P<0.00001). Ribotype 027 isolates were frequently moxifloxacin-resistant (92.2%
      of isolates) and multidrug-resistant (49.5%). Fidaxomicin demonstrated the
      greatest in vitro potency (lowest MIC90, 0.5 MUg/mL; lowest maximum MIC, 2
      MUg/mL) of eight antimicrobial agents tested and was the most active agent
      against each of the five commonest ribotypes (MIC90, 0.25-1 MUg/mL).

PMID- 29456072
TI  - Acute illness from Campylobacter jejuni may require high doses while infection
      occurs at low doses.
AB  - Data from a set of different studies on the infectivity and pathogenicity of
      Campylobacter jejuni were analyzed with a multilevel model, allowing for effects
      of host species (nonhuman primates and humans) and different strains of the
      pathogen. All challenge studies involved high doses of the pathogen, resulting in
      all exposed subjects to become infected. In only one study a dose response effect
      (increasing trend with dose) for infection was observed. High susceptibility to
      infection with C. jejuni was found in a joint analysis of outbreaks and challenge
      studies. For that reason four outbreaks, associated with raw milk consumption,
      were also included in the present study. The high doses used for inoculation did
      not cause all infected subjects to develop acute enteric symptoms. The observed
      outcomes are consistent with a dose response effect for acute symptoms among
      infected subjects: a conditional illness dose response relation. Nonhuman
      primates and human volunteers did not appear to have different susceptibilities
      for developing enteric symptoms, but exposure in outbreaks (raw milk) did lead to
      a higher probability of symptomatic campylobacteriosis.

PMID- 29456071
TI  - Evaluation of Sensititre Broth Microdilution Plate for determining the
      susceptibility of carbapenem-resistant Klebsiella pneumoniae to polymyxins.
AB  - Colistin and polymyxin B MICs were determined for 106 carbapenem-resistant
      Klebsiella pneumoniae (CR-Kp) isolates using Sensititre Research Use Only GNX2F
      plates (Thermo Fisher) and compared to CLSI broth macrodilution (BMD) as the
      reference method. For colistin, EUCAST breakpoints were applied and testing of
      isolates with very major (VM) errors was repeated in duplicate by both methods to
      determine a majority result. Essential agreement (MIC +/- one dilution) of GNX2F
      with the reference method was 97.1% for polymyxin B and 92.5% for colistin (7 VM
      errors, 22.6%). After discrepancy testing, there were 28 colistin resistant
      isolates by BMD and essential agreement was 94.3% with 4 VM errors (14.3%).
      Colistin and polymyxin B GNX2F results showed acceptable essential agreement with
      BMD for MICS without interpretation. Colistin VM errors with EUCAST breakpoints
      were due to MIC variability in the 2 to 4 MUg/mL range that could be addressed by
      establishing an intermediate category.

PMID- 29456073
TI  - An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate
      Restricted Diet on Hepatic Steatosis in Humans.
AB  - A carbohydrate-restricted diet is a widely recommended intervention for non
      alcoholic fatty liver disease (NAFLD), but a systematic perspective on the
      multiple benefits of this diet is lacking. Here, we performed a short-term
      intervention with an isocaloric low-carbohydrate diet with increased protein
      content in obese subjects with NAFLD and characterized the resulting alterations
      in metabolism and the gut microbiota using a multi-omics approach. We observed
      rapid and dramatic reductions of liver fat and other cardiometabolic risk factors
      paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large
      increases in serum beta-hydroxybutyrate concentrations, reflecting increased
      mitochondrial beta-oxidation; and (3) rapid increases in folate-producing
      Streptococcus and serum folate concentrations. Liver transcriptomic analysis on
      biopsy samples from a second cohort revealed downregulation of the fatty acid
      synthesis pathway and upregulation of folate-mediated one-carbon metabolism and
      fatty acid oxidation pathways. Our results highlight the potential of exploring
      diet-microbiota interactions for treating NAFLD.

PMID- 29456074
TI  - Histone deacetylases (HDACs) as therapeutic target for depressive disorders.
AB  - Major depressive disorder (MDD) represents approximately 40% of the disability
      caused by mental illnesses globally. The poorly understood pathophysiology and
      limited efficiency of pharmacological treatment (based primarily on the
      principles of the monoaminergic hypothesis) make depression a serious medical,
      public and socio-economical problem. An increasing number of studies suggest that
      epigenetic modifications (alterations in gene expression that are not due to
      changes in DNA sequence) in certain brain regions and neural circuits represent a
      key mechanism through which environmental factors interact with individual's
      genetic constitution to affect risk of mental disorders. Accordingly, chromatin
      based epigenetic regulation seems to be a promising direction for the development
      of new, more effective antidepressant drugs. Recently, several inhibitors of
      histone deacetylases (HDAC) have been extensively studied in the context of
      antidepressant action. So far, none of them has been used to treat depression in
      humans due to the low selectivity for specific HDAC isoforms, and consequently, a
      risk of serious adverse events. In this review, we focus on the HDAC inhibitors
      (HDACi) with the greatest antidepressant efficacy and their activity in the
      preclinical studies. Moreover, we discuss their potential therapeutic usefulness
      in depression and the main limitations.

PMID- 29456075
TI  - Qualitative Analysis of a Cultural Dexterity Program for Surgeons: Feasible,
      Impactful, and Necessary.
AB  - OBJECTIVES: Ineffective cross-cultural communication contributes to adverse
      outcomes for minority patients. To address this, the authors developed a novel
      curriculum for surgical residents built on the principle of cultural dexterity,
      emphasizing adaptability to clinical and sociocultural circumstances to tailor
      care to the needs of the individual patient. This study's objective was to
      evaluate the feasibility, acceptability, and perception of this program upon
      conclusion of its first year. DESIGN, SETTING, AND PARTICIPANTS: The curriculum
      was implemented at 3 general surgery programs. The flipped classroom model
      combined independent study via e-learning modules with interactive role-playing
      sessions. Sessions took place over 1 academic year. Four focus groups were held,
      each with 6 to 9 participants, to gain feedback on the curriculum. Focus groups
      were recorded and transcribed, and the data were analyzed using a grounded theory
      approach. RESULTS: Five major themes emerged: (1) Role modeling from senior
      colleagues is integral in developing communication/interpersonal skills and
      attitudes toward cultural dexterity. (2) Cultural dexterity is relevant to the
      provision of high-quality surgical care. (3) Barriers to providing culturally
      dexterous care exist at the system level. (4) "Buy-in" at all levels of the
      institution is necessary to implement the principles of cultural dexterity. (5)
      The shared experience of discussing the challenges and triumphs of caring for a
      diverse population was engaging and impactful. CONCLUSION: Early implementation
      of the curriculum revealed that the tension between surgical residents' desire to
      improve their cultural dexterity and systemic/practical obstacles can be
      resolved. Combining surgically relevant didactic materials with experiential
      learning activities can change the paradigm of cross-cultural training.

PMID- 29456076
TI  - Inhaled magnesium sulfate in the treatment of acute asthma in children.

PMID- 29456077
TI  - Talus Fracture of the Medial Tubercle of the Posterior Process: Interposition of
      the Flexor Hallucis Longus Tendon.
AB  - Talus fracture of the medial tubercle of the posterior process is rare. This type
      of fracture can be easily missed, because it is difficult to identify on plain
      radiographs of the ankle. Oblique radiographs with external rotation, computed
      tomography, and magnetic resonance imaging (MRI) of the ankle are useful for
      making an accurate diagnosis. However, even with an early diagnosis, the
      treatment guidelines for talus fractures of the posterior medial tubercle have
      not yet been established. The flexor hallucis longus (FHL) tendon, which passes
      through the groove between the medial and lateral tubercles of the posterior
      process of the talus, can interpose between the fracture sites and interrupt
      fracture reduction. MRI might be the best imaging modality for the identification
      of the interposed FHL tendon. We report a case in which talus fracture of the
      posterior medial tubercle was treated by open reduction and internal fixation
      owing to an interposed FHL tendon that was confirmed by MRI. MRI is the
      recommended imaging study of choice for talus fractures of the posterior medial
      tubercle owing to the possibility of an interposed FHL tendon.

PMID- 29456078
TI  - Transmalleolar Approach for Arthroscopy-Assisted Headless Screw Fixation of an
      Osteochondral Talar Dome Fracture.
AB  - Displaced osteochondral fractures of the body of talus quite often require a
      malleolar osteotomy to gain access to the fracture fragment during internal
      fixation. We describe a case report in which access to a displaced osteochondral
      fracture of the lateral talar dome was achieved using an arthroscopy-assisted
      fibular tunnel approach. This technique resulted in satisfactory fracture healing
      and a satisfactory clinical outcome.

PMID- 29456080
TI  - NEMO Links Nuclear Factor-kappaB to Human Diseases: (Trends Mol Med. 23, 1138
      1155; 2017).

PMID- 29456079
TI  - Phase IV randomized clinical study: Peginterferon alfa-2a with adefovir or
      entecavir pre-therapy for HBeAg-positive chronic hepatitis B.
AB  - BACKGROUND: Efficacy of sequential therapy with nucleos(t)ide analogues and
      interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)
      positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess
      efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV)
      followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg
      positive. METHODS: This randomized, placebo-controlled, double-blind trial was
      conducted at nine sites in Taiwan from April 2010 to October 2013. Patients (N =
      280) were randomized 1:1:1 to receive placebo, ETV or ADV alone for four weeks,
      combined with PEG-IFN alfa-2a for two weeks, then PEG-IFN alfa-2a alone for 46
      weeks. The primary efficacy end point was HBeAg seroconversion at 48 weeks post
      treatment. RESULTS: No significant differences were observed among groups for
      HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3%; PEG-IFN alfa-2a+ETV, 29.5%;
      and PEG-IFN alfa-2a+ADV, 27.4%), HBeAg loss (37.4%, 32.2%, and 28.6%,
      respectively) or change in hepatitis B surface antigen (HBsAg) levels from
      baseline (-0.56 IU/mL, -0.60 IU/mL, and -0.41 IU/mL, respectively). However,
      hepatitis B virus DNA levels were higher with PEG-IFN alfa-2a+placebo than PEG
      IFN alfa+ETV at week 64 (p = 0.0412), 76 (p = 0.0311), and 88 (p = 0.0113), and
      alanine aminotransferase (ALT) normalization rate was higher with PEG-IFN alfa
      2a+placebo than PEG-IFN alfa-2a+ADV (p = 0.0283) or PEG-IFN alfa-2a+ETV (p =
      0.0369) at week 88. Sub-analysis of results revealed an association between on
      treatment HBsAg and ALT levels and efficacy 48 weeks post-treatment. Safety was
      comparable among treatment groups. CONCLUSION: Pre-therapy with ADV or ETV
      followed by PEG-IFN alfa-2a is not superior to PEG-IFN alfa-2a monotherapy in
      Taiwanese patients with HBeAg-positive CHB. CLINICAL TRIAL ID: NCT: 00922207.

PMID- 29456081
TI  - Lysozyme Counteracts beta-Lactam Antibiotics by Promoting the Emergence of L-Form
      Bacteria.
AB  - beta-lactam antibiotics inhibit bacterial cell wall assembly and, under classical
      microbiological culture conditions that are generally hypotonic, induce explosive
      cell death. Here, we show that under more physiological, osmoprotective
      conditions, for various Gram-positive bacteria, lysis is delayed or abolished,
      apparently because inhibition of class A penicillin-binding protein leads to a
      block in autolytic activity. Although these cells still then die by other
      mechanisms, exogenous lytic enzymes, such as lysozyme, can rescue viability by
      enabling the escape of cell wall-deficient "L-form" bacteria. This protective L
      form conversion was also observed in macrophages and in an animal model,
      presumably due to the production of host lytic activities, including lysozyme.
      Our results demonstrate the potential for L-form switching in the host
      environment and highlight the unexpected effects of innate immune effectors, such
      as lysozyme, on antibiotic activity. Unlike previously described dormant
      persisters, L-forms can continue to proliferate in the presence of antibiotic.

PMID- 29456082
TI  - Identification of piRNA Binding Sites Reveals the Argonaute Regulatory Landscape
      of the C. elegans Germline.
AB  - piRNAs (Piwi-interacting small RNAs) engage Piwi Argonautes to silence
      transposons and promote fertility in animal germlines. Genetic and computational
      studies have suggested that C. elegans piRNAs tolerate mismatched pairing and in
      principle could target every transcript. Here we employ in vivo cross-linking to
      identify transcriptome-wide interactions between piRNAs and target RNAs. We show
      that piRNAs engage all germline mRNAs and that piRNA binding follows microRNA
      like pairing rules. Targeting correlates better with binding energy than with
      piRNA abundance, suggesting that piRNA concentration does not limit targeting. In
      mRNAs silenced by piRNAs, secondary small RNAs accumulate at the center and ends
      of piRNA binding sites. In germline-expressed mRNAs, however, targeting by the
      CSR-1 Argonaute correlates with reduced piRNA binding density and suppression of
      piRNA-associated secondary small RNAs. Our findings reveal physiologically
      important and nuanced regulation of individual piRNA targets and provide evidence
      for a comprehensive post-transcriptional regulatory step in germline gene
      expression.

PMID- 29456083
TI  - Placeholder Nucleosomes Underlie Germline-to-Embryo DNA Methylation
      Reprogramming.
AB  - The fate and function of epigenetic marks during the germline-to-embryo
      transition is a key issue in developmental biology, with relevance to stem cell
      programming and transgenerational inheritance. In zebrafish, DNA methylation
      patterns are programmed in transcriptionally quiescent cleavage embryos;
      paternally inherited patterns are maintained, whereas maternal patterns are
      reprogrammed to match the paternal. Here, we provide the mechanism by
      demonstrating that "Placeholder" nucleosomes, containing histone H2A variant
      H2A.Z(FV) and H3K4me1, virtually occupy all regions lacking DNA methylation in
      both sperm and cleavage embryos and reside at promoters encoding housekeeping and
      early embryonic transcription factors. Upon genome-wide transcriptional onset,
      genes with Placeholder become either active (H3K4me3) or silent (H3K4me3/K27me3).
      Notably, perturbations causing Placeholder loss confer DNA methylation
      accumulation, whereas acquisition/expansion of Placeholder confers DNA
      hypomethylation and improper gene activation. Thus, during transcriptionally
      quiescent gametic and embryonic stages, an H2A.Z(FV)/H3K4me1-containing
      Placeholder nucleosome deters DNA methylation, poising parental genes for either
      gene-specific activation or facultative repression.

PMID- 29456084
TI  - Rescue of Fragile X Syndrome Neurons by DNA Methylation Editing of the FMR1 Gene.
AB  - Fragile X syndrome (FXS), the most common genetic form of intellectual disability
      in males, is caused by silencing of the FMR1 gene associated with
      hypermethylation of the CGG expansion mutation in the 5' UTR of FMR1 in FXS
      patients. Here, we applied recently developed DNA methylation editing tools to
      reverse this hypermethylation event. Targeted demethylation of the CGG expansion
      by dCas9-Tet1/single guide RNA (sgRNA) switched the heterochromatin status of the
      upstream FMR1 promoter to an active chromatin state, restoring a persistent
      expression of FMR1 in FXS iPSCs. Neurons derived from methylation-edited FXS
      iPSCs rescued the electrophysiological abnormalities and restored a wild-type
      phenotype upon the mutant neurons. FMR1 expression in edited neurons was
      maintained in vivo after engrafting into the mouse brain. Finally, demethylation
      of the CGG repeats in post-mitotic FXS neurons also reactivated FMR1. Our data
      establish that demethylation of the CGG expansion is sufficient for FMR1
      reactivation, suggesting potential therapeutic strategies for FXS.

PMID- 29456085
TI  - What is the Role of Reversal Agents in the Management of Emergency Department
      Patients with Dabigatran-Associated Hemorrhage?
AB  - BACKGROUND: In 2010, the U.S. Food and Drug Administration (FDA) approved
      dabigatran as the first non-warfarin oral anticoagulant for use in the United
      States. At the time of FDA approval, there was no antidote or effective treatment
      for dabigatran-induced hemorrhage. In 2015, the FDA approved idarucizumab for the
      treatment of dabigatran-induced hemorrhage. The purpose of this clinical practice
      statement is to evaluate the role of select reversal agents in the management of
      patients with dabigatran-associated bleeding. METHODS: A PubMed literature review
      was completed to identify studies that investigated the role of reversal agents
      in the management of emergency department patients with dabigatran-associated
      hemorrhage. Articles included were those published in the English language
      between January 2010 and January 2017, enrolled human subjects, and limited to
      the following types: randomized controlled trials, prospective trials, meta
      analyses, and retrospective cohort studies. Review articles, case series, and
      case reports were not included in this review. All selected articles then
      underwent a structured review by the authors. RESULTS: Six hundred fifty-two
      articles were identified in the search. After use of predetermined inclusion and
      exclusion criteria, six articles were selected for structured review. CONCLUSION:
      The clinical efficacy of activated prothrombin complex concentrates,
      idarucizumab, and recombinant factor VIIa remains unclear until further research
      is performed. Activated prothrombin complex concentrates, idarucizumab, and
      recombinant factor VIIa may be considered in patients with serious bleeding from
      dabigatran, after careful consideration of possible benefits and risks.

PMID- 29456086
TI  - Low-Dose Propofol for Pediatric Migraine: A Prospective, Randomized Controlled
      Trial.
AB  - BACKGROUND: Migraine headaches are a common reason for pediatric emergency
      department (ED) visits. Small studies suggest the potential efficacy of sub
      anesthetic doses of propofol for migraine with a favorable side effect profile
      and potentially decreased length of stay (LOS). OBJECTIVE: The objective of this
      study was to compare the efficacy of low-dose propofol (LDP) to standard therapy
      (ST) in pediatric migraine treatment. METHODS: We conducted a prospective,
      pragmatic randomized controlled trial from April 2014 through June 2016 in the ED
      at two pediatric hospitals. Patients aged 7-19 years were eligible if they were
      diagnosed with migraine by the emergency physician and had a presenting visual
      analog pain score (VAS) of 6-10. Primary outcome was the percent of pain
      reduction. Secondary outcomes were ED LOS, 24-h rebound headache, return visits
      to the ED, and adverse reactions. RESULTS: Seventy-four patients were enrolled,
      but 8 were excluded, leaving 66 patients in the final analysis (36 ST, 30 LDP).
      Pain reduction was 59% for ST and 51% for LDP (p = 0.34) with 72.2% vs. 73.3%
      achieving a VAS <= 4 with initial therapy (p = 0.92). There was a nonsignificant
      trend toward shorter median LOS from drug administration to final disposition
      favoring propofol (79 min vs. 111 min; p = 0.09). Rebound headache was
      significantly more common in the ST vs. LDP group (66.7% vs. 25.0%; p = 0.01).
      CONCLUSIONS: LDP did not achieve better pain reduction than ST, however, LDP was
      associated with significantly fewer rebound headaches and a nonsignificant trend
      toward shorter median LOS from drug administration to disposition.

PMID- 29456087
TI  - Successful Interprofessional Approach to Development of a Resuscitative
      Endovascular Balloon Occlusion of the Aorta Program at a Community Trauma Center.
AB  - BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is
      a relatively innovative procedure designed to control critical non-compressible
      torso hemorrhage. In the United States, this procedure is currently in active use
      at only a small number of trauma centers. OBJECTIVE: We describe how we developed
      our REBOA program at an independent academic-affiliated community trauma center.
      DISCUSSION: Through a close interprofessional and multidisciplinary collaboration
      led by emergency physicians and trauma surgeons, we were able to successfully
      develop our program. CONCLUSIONS: Successful implementation of a REBOA program
      requires close attention to multimodal training, interprofessional roles, team
      dynamics, financial considerations, and quality assurance processes to safely
      deliver this potentially life-saving procedure to our trauma patient population.

PMID- 29456088
TI  - Apalutamide shows efficacy in prostate cancer.

PMID- 29456089
TI  - MSM in England to be offered free HPV vaccination.

PMID- 29456090
TI  - Public Health England publishes e-cigarette review.

PMID- 29456092
TI  - Indications for and diagnostic yield of capsule endoscopy in the elderly.
AB  - INTRODUCTION AND AIMS: The growing elderly population and wide use of capsule
      endoscopy have led to a higher number of procedures in those patients. The aim of
      the present study was to assess the usefulness of capsule endoscopy in older
      patients. MATERIALS AND METHODS: All consecutive patients undergoing capsule
      endoscopy at our center within the time frame of 2004-2016 were classified as
      older (>=75 years of age) and younger. Findings and diagnostic yield were
      comparatively assessed. RESULTS: Of 2311 patients (mean age: 59.5 +/- 19.23
      years, 44.48% male), 648 were in the older group and 1663 in the younger group.
      Gastric transit time was shorter in the older patients (p=0.001), whereas small
      bowel transit time was shorter in the younger patients (p<0.001). Overall
      diagnostic yield in the elderly was higher (50.66% vs. 41.19%, p<0.001). Obscure
      gastrointestinal bleeding was the most frequent indication for capsule endoscopy
      in the elderly (90.4% vs. 53.77%, p<0.001), achieving a higher diagnostic yield
      than in the younger population (51.47% vs. 42.76%, p=0.002), whereas Crohn's
      disease, suspected or known neoplasms/polyps, malabsorption syndrome, and
      abdominal pain were the indications in the younger patient group. Such
      indications were rare in the older group. Vascular lesions and active bleeding
      were more frequently diagnosed in the older patients, whereas ulcers/erosions and
      mucosal atrophy were more common in the younger patients (p<0.001). CONCLUSIONS:
      Capsule endoscopy achieved a higher overall diagnostic yield in the elderly
      patients. Obscure gastrointestinal bleeding indication for capsule endoscopy was
      much more frequent in the advanced-age group and had a higher diagnostic yield.

PMID- 29456091
TI  - Frequency of human papillomavirus infection in patients with gastrointestinal
      cancer.
AB  - INTRODUCTION AND AIM: Cancer is the result of the interaction of genetic and
      environmental factors. It has recently been related to viral infections, one of
      which is human papillomavirus. The aim of the present study was to describe the
      frequency of human papillomavirus infection in patients with digestive system
      cancers. MATERIALS AND METHODS: A prospective, multicenter, observational study
      was conducted on patients with gastrointestinal cancer at 2public healthcare
      institutes in Veracruz. Two tumor samples were taken, one for histologic study
      and the other for DNA determination of human papillomavirus and its genotypes.
      Anthropometric variables, risk factors, sexual habits, tumor location, and
      histologic type of the cancer were analyzed. Absolute and relative frequencies
      were determined using the SPSS version 24.0 program. RESULTS: Fifty-three
      patients were studied. They had gastrointestinal cancer located in: the colon
      (62.26%), stomach (18.87%), esophagus (7.55%), rectum (7.55%), and small bowel
      (3.77%). Human papillomavirus was identified in 11.32% of the patients, 66.7% of
      which corresponded to squamous cell carcinoma and 33.3% to adenocarcinoma. Only
      genotype 18 was identified. Mean patient age was 61.8+/-15.2 years, 56.60% of the
      patients were men, and 43.40% were women. A total of 15.8% of the patients had a
      family history of cancer and 31.6% had a personal history of the disease, 38.6%
      were tobacco smokers, and 61.4% consumed alcohol. Regarding sex, 5.3% of the
      patients said they were homosexual, 3.5% were bisexual, 29.8% engaged in oral
      sex, and 24.6% in anal sex. CONCLUSIONS: Our study showed that human
      papillomavirus infection was a risk factor for the development of
      gastrointestinal cancer, especially of squamous cell origin.

PMID- 29456093
TI  - Validation of the French-Canadian Pelvic Girdle Questionnaire.
AB  - OBJECTIVE: Pain in the pelvic girdle area is commonly reported during pregnancy
      and the postpartum period, and its impact on quality of life is considerable. The
      Pelvic Girdle Questionnaire (PGQ), developed in 2011 in Norway, is the only
      condition-specific tool assessing pelvic girdle pain-related symptoms and
      disability. The questionnaire was recently translated and adapted for the French
      Canadian population. The objective of this study was to assess the measurement
      properties of the previously translated French-Canadian PGQ. METHODS: Eighty-two
      women with pelvic girdle pain were included in this validation study. The French
      Canadian PGQ, pain intensity Numeric Rating Scale, and Oswestry Disability Index
      were completed by participants at baseline, 48 hours later, and 3 to 6 months
      later to assess test-retest reliability, construct validity, responsiveness,
      floor and ceiling effects, and internal consistency. RESULTS: Reliability
      analyses indicated an intraclass correlation coefficient of 0.841 (95% confidence
      interval [CI] 0.750-0.901) for the global score. Construct validity analyses
      indicated a Spearman rank correlation coefficient of 0.696 with the Oswestry
      Disability Index. Responsiveness analyses identified an effect size of 0.908 (95%
      CI 0.434-1.644) and an area under the receiver operating characteristics curve of
      0.823 (95% CI 0.692-0.953). There was no floor or ceiling effect, and internal
      consistency analyses indicated a Cronbach alpha of .933 for the activity subscale
      and .673 for the symptom subscale. CONCLUSION: Overall, the French-Canadian
      version of the PGQ is reliable, valid, and responsive, suggesting that it can be
      implemented in both research and clinical settings to assess functional
      limitations in pregnant and postpartum women.

PMID- 29456094
TI  - Association Among Opioid Use, Treatment Preferences, and Perceptions of Physician
      Treatment Recommendations in Patients With Neck and Back Pain.
AB  - OBJECTIVE: The purpose of this study was to explore the relationship between self
      reported use of opioids by patients with neck and back pain and their
      demographics, pain characteristics, treatment preferences, and recollections of
      their physicians' opinions regarding treatment options. METHODS: We analyzed 2017
      Gallup Poll survey data from 1680 US adults who had substantial spine pain in the
      past year and used logistic regression to explore the aforementioned
      relationships. RESULTS: Our multiple regression analysis indicated that adults
      with neck or back pain severe enough to have sought health care within the last
      year were more likely to have used opioids in the last year if they (in
      descending order of marginal impact) had pain that had lasted 1 year or less
      (adjusted odds ratio [OR] = 34.35, 90% confidence interval [CI] 17.56-74.32);
      concurrently used benzodiazepines (OR = 6.02, 90% CI 2.95-12.33); had Medicaid as
      an insurance source (OR = 3.29, 90% CI 1.40-7.48); indicated that they preferred
      to use pain medications prescribed by a doctor to treat physical pain (OR = 3.24,
      90% CI 1.88-5.60); or were not college educated (OR = 1.83, 90% CI 1.05-3.25).
      Compared with patients aged 65 years and older, those aged 18 to 34 years were
      less likely to have used opioids in the past year (OR = 0.09, 90% CI 0.01-0.40,
      0.50 for 95% CI). Respondents' perceptions of medical doctors' positive or
      negative opinions regarding a variety of neck and back pain treatment options
      were not significantly associated with opioid use. CONCLUSIONS: Patients with
      neck and back pain who use opioids differ from those who do not use opioids in
      that they are more likely to have pain that is of shorter duration, to use
      benzodiazepines, to have Medicaid as an insurance source, and to prefer to use
      pain medications. Those characteristics should be considered when developing
      opioid use prevention strategies.

PMID- 29456095
TI  - Comparison of Median Nerve Mechanosensitivity and Pressure Pain Threshold in
      Patients With Nonspecific Neck Pain and Asymptomatic Individuals.
AB  - OBJECTIVE: The purpose of this study was to investigate the presence of median
      nerve mechanosensitivity by comparing median nerve neurodynamic test results of
      patients with nonspecific neck pain (NNP) and asymptomatic individuals. METHODS:
      A total of 40 patients (30 women, 10 men) with NNP between the ages of 21 and 62
      years (39.53 +/- 10.18 years) and 38 asymptomatic individuals (23 women, 15 men)
      between the ages of 18 and 60 years (37.13 +/- 9.64 years) participated in the
      study. Pressure pain threshold was assessed with digital pressure algometer,
      cervical joint range of motion was assessed with a universal goniometer, and
      median nerve mechanosensitivity was assessed with Upper Limb Neurodynamic Test 1
      (ULNT1). The test step where the first sensory response was given, the location
      and character of the sensory response, and the final elbow extension angle were
      recorded during ULNT1. RESULTS: Patients with NNP had significantly decreased
      pressure pain threshold (P < .001), decreased range of motion of cervical flexion
      (P < .001), and decreased cervical lateral flexion (P = .001) compared with
      asymptomatic individuals, whereas no change was identified in range of motion of
      rotation (P = .100). In ULNT1, 45% of patients with NNP reported pain and 40% of
      them reported stretch. A total of 65% of asymptomatic individuals reported
      stretch, and 13% of them reported pain. It was identified in ULNT1 that final
      elbow extension angle was lower in the NNP group compared with asymptomatic
      individuals (P = .008). CONCLUSION: Median nerve mechanosensitivity increased,
      pressure pain threshold decreased, and active neck motion was limited in
      individuals with NNP compared with asymptomatic individuals.

PMID- 29456096
TI  - Cholescintigraphic patterns in a IBS patient with postprandial diarrhea.

PMID- 29456097
TI  - The timing of early therapeutic strategies has a significant impact on Crohn's
      disease prognosis.
AB  - BACKGROUND: Abdominal surgery and immunosuppressive pharmacological treatments
      are two different therapeutic options used to manage Crohn disease. This study
      aimed to determine whether the timing of these interventions had an impact on
      patients' prognosis. METHOD: This manuscript entails a retrospective analysis of
      a multicentric cohort involving 498 CD patients that had bowel surgery after
      diagnosis and prior to immunosuppression treatments. Two endpoints were
      considered: the occurrence of disabling disease and the need to undergo further
      bowel surgeries. RESULTS: Disabling disease affected 71% of all patients, whereas
      39% needed reoperation. The odds ratios (OR) of being affected by disabling
      disease were higher when patients had upper tract involvement [3.412 [1.285
      9.061]], perianal disease (2.270 [1.239-4.157]) and a longer time elapsed from
      diagnosis to first surgery (13-36 months: 2.576 [1.207-5.500]). On the other
      hand, the need to undergo further surgical interventions was significantly
      increased in smoking patients (2.294 [1.187-4.432]), but decreased in patients
      who started pharmacological therapy not later than six months after the first
      surgery (0.256 [0.093-0.704]). CONCLUSIONS: Our results suggest that the timing
      of therapeutic strategies does affects the CD outcomes: whereas an early surgery
      had a preventive effect on the occurrence of disabling events, the introduction
      of medication in the first semester after surgery had a preventive effect on the
      need for reoperation.

PMID- 29456098
TI  - ArF excimer laser debrides burns without destruction of viable tissue: A pilot
      study.
AB  - INTRODUCTION: Recent evidence indicates that early removal of eschar by
      tangential debridement can promote healing. Laser debridement can be used for
      debridement of areas that prove challenging for debridement using tangential
      excision. In particular, irradiation with an ArF excimer laser ablates desiccated
      eschar and is self-terminating, preserving hydrated or viable tissue. METHODS:
      Thermal burns were created on the flanks of two outbred, female Yorkshire pigs
      using aluminum bars heated to 70 degrees C and applied for different lengths of
      time. Three days after injury, burns were debrided using an ArF excimer laser
      (193nm). Tissue was harvested immediately after debridement and 7days after
      debridement (10days after burn). RESULTS: Data from a pilot study demonstrates
      that ArF excimer laser irradiation removes burn eschar and promotes healing at
      10days after burn. ArF excimer laser debridement is self-terminating and
      preserves underlying and adjacent perfused tissue. Potentially, this modality
      would be ideal for the complex curvilinear structures of the body.

PMID- 29456099
TI  - Time to start putting down the knife: A systematic review of burns excision tools
      of randomised and non-randomised trials.
AB  - AIMS: Dermal preservation during acute burn excision is key to obtaining superior
      healing/scar outcomes, however, determining the most appropriate excision tool is
      an ongoing challenge. Novel tool development means the knife is no longer our
      only option, yet for the majority it remains the gold standard. This systematic
      review aims to evaluate evidence for burns excision approaches
      (knife/hydrosurgery/enzymatic). METHODS: CENTRAL, EMBASE, MEDLINE (1946-2017)
      were searched with MeSH terms: 'debridement', 'burns', 'sharp', 'enzymatic',
      'hydrosurgery'. Relevant randomised control trials (RCTs)/non-randomised
      controlled case series/trials were extracted/analysed. In vitro/burn non-specific
      studies were excluded. Main methodological parameters were intervention/excision
      efficacy. RESULTS: Eighteen articles met inclusion criteria (n=7148): three were
      RCTs, involving comparator enzymatic (NexoBridTM (EDNX)) or hydrosurgical
      (VersajetTM) excision to surgical Standard of Care. Both showed statistically
      significant decreased need for excisional excision and auto-grafting by viable
      tissue preservation allowing spontaneous healing by epithelialisation.
      CONCLUSION: Level 1 Evidence comparing excision modalities for acute burns is
      sparse. Although early excision with a knife is still often considered best
      practice, there is no tool choice consensus or robust comparison with alternate,
      possibly superior, tools. EDNX or VersajetTM should be considered alternatively.
      Further RCTs are indicated, with regards final scar outcomes and to allow
      consensus within current evidence.

PMID- 29456101
TI  - Ligand-based modeling of Akt3 lead to potent dual Akt1/Akt3 inhibitor.
AB  - Akt1 and Akt3 are important serine/threonine-specific protein kinases involved in
      G2 phase required by cancer cells to maintain cell cycle and to prevent cell
      death. Accordingly, inhibitors of these kinases should have potent anti-cancer
      properties. This prompted us to use pharmacophore/QSAR modeling to identify
      optimal binding models and physicochemical descriptors that explain bioactivity
      variation within a set of 74 diverse Akt3 inhibitors. Two successful orthogonal
      pharmacophores were identified and further validated using receiver operating
      characteristic (ROC) curve analyses. The pharmacophoric models and associated
      QSAR equation were applied to screen the national cancer institute (NCI) list of
      compounds for new Akt3 inhibitors. Six hits showed significant experimental anti
      Akt3 IC50 values, out of which one compound exhibited dual low micromolar anti
      Akt1 and anti-Akt3 inhibitory profiles.

PMID- 29456102
TI  - The prognostic capacity of transvaginal hydrolaparoscopy to predict non-IVF
      conception.
AB  - Transvaginal hydrolaparoscopy (THL) is performed to investigate tubal pathology
      in subfertile women. This retrospective multicentre cohort study investigated the
      results of THL and subsequent pregnancy rates. Between 2000 and 2011, 1033
      subfertile women participated in the study. The primary outcome measure was
      intrauterine pregnancy, either after natural conception or after treatment with
      intrauterine insemination or ovulation induction. Cumulative intrauterine
      pregnancy rates were calculated using Kaplan-Meier analysis and fecundity rate
      ratios (FRR) were established. THL showed bilateral patent tubes in 83%, one
      sided tubal occlusion in 12.4% and bilateral tubal occlusion in 4.6% of women.
      Cumulative intrauterine pregnancy rates after 36 months were 52% for women with
      bilateral patent tubes, 44% for one-sided tubal occlusion (FRR 1.04; 95%
      confidence interval [CI], 0.78 to 1.39) and 7% for bilateral tubal occlusion (FRR
      0.13; 95% CI, 0.04 to 0.43). Endometriosis was diagnosed in 6.4%, and adhesions
      in 9.1%, while 3.9% of women had both. Corresponding FRR were 0.73 (95% CI, 0.49
      to 1.09), 0.68 (95% CI, 0.46 to 1.02) and 0.42 (95% CI, 0.20 to 0.84). In
      conclusion, women with bilateral tubal occlusion or a combination of
      endometriosis and adhesions found on THL significantly reduced chances of natural
      conception.

PMID- 29456100
TI  - The Coding Regions of Germline mRNAs Confer Sensitivity to Argonaute Regulation
      in C. elegans.
AB  - Protein-coding genes undergo a wide array of regulatory interactions with factors
      that engage non-coding regions. Open reading frames (ORFs), in contrast, are
      thought to be constrained by coding function, precluding a major role in gene
      regulation. Here, we explore Piwi-interacting (pi)RNA-mediated transgene
      silencing in C. elegans and show that marked differences in the sensitivity to
      piRNA silencing map to the endogenous sequences within transgene ORFs.
      Artificially increasing piRNA targeting within the ORF of a resistant transgene
      can lead to a partial yet stable reduction in expression, revealing that piRNAs
      not only silence but can also "tune" gene expression. Our findings support a
      model that involves a temporal element to mRNA regulation by germline Argonautes,
      likely prior to translation, and suggest that piRNAs afford incremental control
      of germline mRNA expression by targeting the body of the mRNA, including the
      coding region.

PMID- 29456103
TI  - Straddling care and education: Developing interprofessional collaboration through
      a hotspotting service learning project.
AB  - Interprofessional (IP) team work has been shown to decrease burnout and improve
      care and decrease costs. However, institutional barriers have challenged adoption
      in practice and education. Faculty and students are turning to IP service
      learning projects to help students gain experience and provide needed services.
      This paper highlights a "hotspotting" program where students from different
      health professions work collaboratively to improve high utilizing patients'
      health. Benefits, challenges and preliminary results including cost savings and
      student efficacy are shared. Institutions should surmount barriers that make
      hotspotting service-learning challenging as IP team-based experiences prepare
      students for the workplace and can help mitigate burnout.

PMID- 29456104
TI  - Methodological considerations for developmental longitudinal fMRI research.
AB  - There has been a large spike in longitudinal fMRI studies in recent years, and so
      it is essential that researchers carefully assess the limitations and challenges
      afforded by longitudinal designs. In this article, we provide an overview of
      important considerations for longitudinal fMRI research in developmental samples,
      including task design, sampling strategies, and group-level analyses. We first
      discuss considerations for task designs, weighing the pros and cons of many
      commonly used tasks, as well as outlining how the tasks may be impacted by
      repeated exposure. Secondly, we review the types of group-level analyses that can
      be conducted on longitudinal fMRI data, analyses which must account for repeated
      measures. Finally, we review and critique recent longitudinal studies that have
      emerged in the past few years.

PMID- 29456105
TI  - Marine bis-gamma-pyrone polypropionates of onchidione family and their effects on
      the XBP1 gene expression.
AB  - Two additional new members of the onchidione family, 16-epi-onchidione (1) and 4
      epi-onchidione (2), co-occurring with six previously reported bis-gamma-pyrone
      polypropionates including onchidione (3), were isolated from the marine pulmonate
      Onchidium sp. Their structures were determined by extensive spectroscopic
      analysis and by comparison with 3 and onchidione-related derivatives. The
      absolute configuration of 1 was established by X-ray diffraction analysis
      employing graphite monochromated Cu Kalpha radiation (lambda = 0.71073 A) with
      small Flack parameter 0.08. In addition, the absolute stereochemistry of
      previously reported onchidionol (6) was confirmed by the X-ray diffraction
      analysis. Some of the isolated compounds showed significant activation effects on
      the splicing of XBP1 mRNA as ER stress modulators to inhibit the growth of
      tumors.

PMID- 29456106
TI  - Design, synthesis and anticancer activities evaluation of novel 5H
      dibenzo[b,e]azepine-6,11-dione derivatives containing 1,3,4-oxadiazole units.
AB  - Rucaparib and PJ34 were used as the structural model for the design of novel 5H
      dibenzo[b,e]azepine-6,11-dione derivatives containing 1,3,4-oxadiazole units. And
      target compounds were successfully synthesized through a 3-step synthetic
      strategy. All target compounds were screened for their anti-proliferative effects
      against OVCAR-3 cell line. Preliminary biological study of these compounds
      provided potent compounds d21 and d22 with better activities than Rucaparib.

PMID- 29456107
TI  - Design, synthesis, and discovery of 5-((1,3-diphenyl-1H-pyrazol-4
      yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones and related derivatives as novel
      inhibitors of mPGES-1.
AB  - Human mPGES-1 has emerged as a promising target in exploring a next generation of
      anti-inflammatory drugs, as selective mPGES-1 inhibitors are expected to
      discriminatively suppress the production of induced PGE2 without blocking the
      normal biosynthesis of other prostanoids including homeostatic PGE2. Therefore,
      this therapeutic approach is believed to reduce the adverse effects associated
      with the application of traditional non-steroidal anti-inflammatory drugs
      (tNSAIDs) and selective COX-2 inhibitors (coxibs). Identified from structure
      based virtue screening, the compound with (Z)-5-benzylidene-2-iminothiazolidin-4
      one scaffold was used as lead in rational design of novel inhibitors. Besides, we
      further designed, synthesized, and evaluated 5-((1,3-diphenyl-1H-pyrazol-4
      yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-triones and structurally related
      derivatives for their in vitro inhibitory activities. According to in vitro
      activity assays, a number of these compounds were capable of inhibiting human
      mPGES-1, with the desirable selectivity for mPGES-1 over COX isozymes.

PMID- 29456108
TI  - Discovery of N-arylpyrroles as agonists of GPR120 for the treatment of type II
      diabetes.
AB  - The discovery of a novel series of N-arylpyrroles as agonists of GPR120 (FFAR4)
      is discussed. One lead compound is a potent GPR120 agonist, has good selectivity
      for related receptor GPR40 (FFAR1), has acceptable PK properties, and is active
      in 2 models of Type 2 Diabetes in mice.

PMID- 29456109
TI  - Synthetic strigolactone analogues reveal anti-cancer activities on hepatocellular
      carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) remains one of the leading causes of death
      worldwide. The complex etiology is attributed to many factors like heredity,
      cirrhosis, hepatitis infections or the dysregulation of the different molecular
      pathways. Nevertheless, the current treatment regimens have either severe side
      effects or tumors gradually acquire resistance upon prolonged use. Thus,
      developing a new selective treatment for HCC is the need of the hour. Many
      anticancer agents derived from plants have been evaluated for their cytotoxicity
      towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered
      class of phytohormones, play a crucial role in the development of plant-root and
      shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic
      effects on different cancer cell lines like prostate, breast, colon and lung. In
      this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and
      evaluated their capability to induce cell proliferation inhibition and apoptosis.
      Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti
      proliferative effects. The SLs analogues TIT3 and TIT7 were found to
      significantly reduce HepG2 cell viability in a dose- and time-dependent manner
      and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected
      cancer cell proliferation, both compounds showed moderate anti-proliferative
      effect on normal cells. Further, migration of cancer cells was suppressed upon
      treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings
      suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects
      on cancer cells most likely through targeting microtubules. SLs analogues could
      be used in future as potential anti-cancer candidates in chemotherapy.

PMID- 29456110
TI  - Synthesis, spectroscopic studies and biological evaluation of acridine
      derivatives: The role of aggregation on the photodynamic efficiency.
AB  - Two new photoactive compounds (1 and 2) derived from the 9-amidoacridine
      chromophore have been synthesized and fully characterized. Their abilities to
      produce singlet oxygen upon irradiation have been compared. The synthesized
      compounds show very different self-aggregating properties since only 1 present a
      strong tendency to aggregate in water. Biological assays were conducted with two
      cell types: hepatoma cells (Hep3B) and human umbilical vein endothelial cells
      (HUVEC). Photodynamic therapy (PDT) studies carried out with Hep3B cells showed
      that non-aggregating compound 2 showed photoxicity, ascribed to the production of
      singlet oxygen, being aggregating compound 1 photochemically inactive. On the
      other hand suspensions of 1, characterized as nano-sized aggregates, have notable
      antiproliferative activity towards this cell line in the dark.

PMID- 29456111
TI  - Methyllucidone inhibits STAT3 activity by regulating the expression of the
      protein tyrosine phosphatase MEG2 in DU145 prostate carcinoma cells.
AB  - During the search for signal transducer and activator of transcription 3 (STAT3)
      inhibitors from natural products, methyllucidone, isolated from Lindera species
      (Lauraceae), was identified as a STAT3 inhibitor. Methyllucidone inhibited STAT3
      phosphorylation at tyrosine 705 in a dose- and time dependent manner in DU145
      prostate cancer cells and suppressed IL-6-induced STAT3 phosphorylation at Tyr
      705 in LNCaP cells. Methyllucidone decreased the expression levels of STAT3
      target genes, such as cyclin D1, cyclin A, Bcl-2, Mcl-1, and survivin.
      Methyllucidone inhibited DU145 cell growth and induced apoptosis by arresting the
      cell cycle at G1 phase. Notably, knockdown of the MEG2 gene by small interfering
      RNA suppressed the ability of methyllucidone to inhibit STAT3 activation.
      Methyllucidone regulates STAT3 activity by modulating MEG2 expression, and our
      results suggest that this compound is a novel inhibitor of the STAT3 pathway and
      may be a useful lead molecule for the development of a therapeutic STAT3
      inhibitor.

PMID- 29456112
TI  - Discovery of DSP-1053, a novel benzylpiperidine derivative with potent serotonin
      transporter inhibitory activity and partial 5-HT1A receptor agonistic activity.
AB  - We have previously shown that SMP-304, a serotonin uptake inhibitor with weak 5
      HT1A partial agonistic activity, may act under high serotonin levels as a 5-HT1A
      antagonist that improves the onset of paroxetine in the rat swimming test.
      However, SMP-304 is mostly metabolized by CYP2D6, indicating limited efficacy
      among individuals and increased side effects. To reduce CYP2D6 metabolic
      contribution and enhance SERT/5-HT1A binding affinity, we carried out a series of
      substitutions at the bromine atom in the left part of the benzene ring of SMP-304
      and replaced the right part of SMP-304 with a chroman-4-one. This optimization
      work led to the identification of the antidepressant candidate DSP-1053 as a
      potent SERT inhibitor with partial 5-HT1A receptor agonistic activity. DSP-1053
      showed low CYP2D6 metabolic contribution and a robust increase in serotonin
      levels in the rat frontal cortex.

PMID- 29456113
TI  - Design, synthesis, and evaluation of the antiproliferative activity of hydantoin
      derived antiandrogen-genistein conjugates.
AB  - Androgen receptor (AR) signaling is vital to the viability of all forms of
      prostate cancer (PCa). With the goal of investigating the effect of simultaneous
      inhibition and depletion of AR on viability of PCa cells, we designed,
      synthesized and characterized the bioactivities of bifunctional agents which
      incorporate the independent cancer killing properties of an antiandrogen and
      genistein, and the AR downregulation effect of genistein within a single
      molecular template. We observed that a representative conjugate, 9b, is much more
      cytotoxic to both LNCaP and DU145 cells relative to the antiandrogen and
      genistein building blocks as single agents or their combination. Moreover,
      conjugate 9b more effectively down regulates cellular AR protein levels relative
      to genistein and induces S phase cell cycle arrest. The promising bioactivities
      of these conjugates warrant further investigation.

PMID- 29456115
TI  - Reply to Letter to the Editor.

PMID- 29456114
TI  - Detection and genetic characterization of Mamastrovirus 5 from Brazilian dogs.
AB  - Mamastrovirus 5 (MAstV5), belonging to the Astroviridae (AstV) family, previously
      known as canine astrovirus or astrovirus-like particles, has been reported in
      several countries to be associated with viral enteric disease in dogs since the
      1980s. Astroviruses have been detected in fecal samples from a wide variety of
      mammals and birds that are associated with gastroenteritis and extra enteric
      manifestations. In the present study, RT-PCR was used to investigate the presence
      of MAstV5 in 269 dog fecal samples. MAstV5 was detected in 26% (71/269) of the
      samples. Interestingly, all MAstV5-positive samples derived from dogs displaying
      clinical signs suggestive of gastroenteritis, other enteric viruses were
      simultaneously detected (canine parvovirus, canine distemper virus, canine
      coronavirus, canine adenovirus and canine rotavirus). Based on genomic sequence
      analysis of MAstV5 a novel classification of the species into four genotypes,
      MAstV5a-MAstV5d, is proposed. Phylogenetic analyses based on the ORF2 amino acid
      sequences, samples described herein grouped into the putative genotype 'a' closed
      related with Chinese samples. Other studies are required to attempt the clinical
      and antigenic implications of these astrovirus genotypes in dogs.

PMID- 29456116
TI  - Influence of topical steroids on intraocular pressure in patients with atopic
      dermatitis.
AB  - BACKGROUND: Topical corticosteroids (TCS) can induce adverse effects, such as
      skin atrophy. Although TCS can cause increases in intraocular pressure (IOP), the
      effects of daily TCS use on IOP have not been fully elucidated. We evaluated the
      clinical doses of TCS and the change in the IOP during the daily treatment of
      atopic dermatitis (AD). METHODS: We collected clinical data on a total of 65
      patients who were diagnosed with AD and underwent 2 or more IOP measurements at
      our hospital. RESULTS: Mean monthly facial steroid volumes of <=11.8 g and <=15.0
      g of TCS were applied to 90% of the patients aged 2-12 years and those aged >=13
      years, respectively. During the treatment, there were no TCS-related increases in
      IOP in any patient. CONCLUSIONS: Our study suggests that TCS might not cause
      increases in IOP at the abovementioned doses. However, the IOP of steroid
      responders is known to be highly responsive to steroids. Therefore, patients who
      have steroids applied to their eyelids had better undergo regular IOP
      measurements at ophthalmological clinics.

PMID- 29456117
TI  - Extraordinary daytime only urinary frequency in childhood: Prevalence, diagnosis,
      and management.
AB  - INTRODUCTION: Since standardization of the ICCS terminology, only two small case
      series of children with extraordinary daytime only urinary frequency (EDOUF) have
      been published. The aims of the present study were i) to describe a large cohort
      of children affected by EDOUF, to evaluate its rate among the main micturition
      pediatric disturbances, and to determine if there is different EDOUF onset among
      seasons; ii) to investigate possible associations with urodynamic abnormalities
      by non-invasive techniques; iii) to evaluate whether postponing micturition
      exercise (PME) can objectively verify the anamnestic data hinting at the EDOUF
      diagnosis; and iv) to determine the effect of postponing micturition at home.
      MATERIAL AND METHODS: We reviewed the records of all patients with EDOUF,
      nocturnal enuresis, and/or overactive bladder firstly examined from March 2012 to
      February 2016. We evaluated post-void residual and bladder wall thickness by
      urinary ultrasound and uroflowmetry and recorded the season in which the EDOUF
      started. Through the PME, the EDOUF diagnosis was confirmed if patients were able
      to postpone micturition reaching at least 80% of the expected bladder capacity
      without showing urinary incontinence. At home, we recommended postponing
      micturition for a maximum of 3 h if EDOUF affected the normal daily activities of
      both children and parents. We set a telephone interview for 3 months later.
      RESULTS: The clinical characteristics of the EDOUF population are shown in the
      Table. The EDOUF rate was 12.1%. The rate of EDOUF onset was significantly lower
      during the summer than in other seasons (p = 0.02) and the OR for onset of EDOUF
      in the summer - compared with the other seasons - was 0.37 (95% CI 0.18-0.74; p =
      0.005). Eighty-five (80.2%) patients reported an intermittent trend of the EDOUF
      with variable periods of improvement and worsening. All the EDOUF patients had
      normal uroflowmetry, 1/106 had post-micturition bladder wall thickness >5 mm and
      one post-void residual. At the PME, 106 out of 106 (100%) patients with EDOUF
      were able to reach at least 80% of the EBC without showing urinary incontinence
      or urgency incontinence. After 3 months, in 98.1% of the patients the symptoms
      had disappeared or improved. DISCUSSION AND CONCLUSIONS: Childhood EDOUF is
      rather common and is generally associated with normal non-invasive urodynamic
      patterns. The PME allows verification of anamnestic data of EDOUF. The sole
      recommendation to postpone micturition for a maximum of 3 h or until the
      micturition postponement became stressful could be considered as a possible
      approach.

PMID- 29456118
TI  - Simulation in paediatric urology and surgery, part 2: An overview of simulation
      modalities and their applications.
AB  - Surgical training has changed radically in the last few decades. The traditional
      Halstedian model of time-bound apprenticeship has been replaced with competency
      based training. In our previous article, we presented an overview of learning
      theory relevant to clinical teaching; a summary for the busy paediatric surgeon
      and urologist. We introduced the concepts underpinning current changes in
      surgical education and training. In this next article, we give an overview of the
      various modalities of surgical simulation, the educational principles that
      underlie them, and potential applications in clinical practice. These modalities
      include; open surgical models and trainers, laparoscopic bench trainers, virtual
      reality trainers, simulated patients and role-play, hybrid simulation, scenario
      based simulation, distributed simulation, virtual reality, and online simulation.
      Specific examples of technology that may be used for these modalities are
      included but this is not a comprehensive review of all available products.

PMID- 29456119
TI  - Prevalence of UTI among Iranian infants with prolonged jaundice, and its main
      causes: A systematic review and meta-analysis study.
AB  - INTRODUCTION: An extremely variable and high prevalence of urinary tract
      infection (UTI) in infants with prolonged jaundice has been reported in Iran.
      However, there is no research from the area that has attempted to estimate pooled
      prevalence of UTI from considerably diverse evidence. Therefore, this systematic
      review and meta-analysis study aimed to estimate the prevalence of UTI in infants
      with prolonged jaundice who were admitted into clinics or hospitals in Iran.
      METHODS: A systematic review and meta-analysis was conducted of published
      articles on UTI prevalence in infants with prolonged jaundice in Iran. Electronic
      databases were searched, including Web of Sciences, PubMed/Medline, Scopus,
      Iranian Scientific Information Database (SID) and Iranmedex, for both English and
      Persian language articles published between January, 2000 and March, 2017. All
      possible combinations of the following keywords were used: jaundice, icterus,
      hyperbilirubinemia during infancy, infection and neonatal. Nine studies that
      reported prevalence of UTI in infants with prolonged jaundice were included. The
      overall prevalence of UTI was estimated using random-effects meta-analysis
      models. RESULTS: A total of 1750 infants were pooled to estimate the overall
      prevalence of UTI in infants with prolonged jaundice. The prevalence reported by
      the studies included in this literature review was extremely variable and ranged
      0.6-53.9%. The overall prevalence was 11% (95% Confidence Interval (CI): 5.0
      18.0), and Escherichia coli was found to be the main cause of UTI. CONCLUSION:
      The overall prevalence of UTI was 11%, and E. coli was the main cause of UTI in
      infants with prolonged jaundice. Screening of UTI should be considered for
      infants with prolonged jaundice.

PMID- 29456120
TI  - Bladder debris on ultrasound as a predictor for positive urine culture in a
      pediatric population.
AB  - INTRODUCTION: Debris within the bladder is commonly seen on ultrasound. The
      etiology of bladder debris is varied and the likelihood that urinary debris
      represents positive urine culture is under investigation. We hypothesize that
      bladder debris will increase the likelihood that a urine culture is positive
      compared to those without bladder debris. METHODS: We performed a retrospective
      review on children aged 0-17 years who had a voiding cystourethrogram with a
      catheterized urinalysis or urine culture, and who also had a renal and bladder
      ultrasound up to 1 week prior, the day of, or up to 2 days after their urine
      studies. Presence of bladder debris and debris severity was recorded. Positive
      urine culture was defined as a single bacterial strain >=50,000 cfu/mL.
      Demographic information, including findings of reflux and hydronephrosis were
      compared. Sensitivity, specificity, and risk ratios were calculated for
      predicting positive urine culture in patients with urinary debris on ultrasound.
      RESULTS: A total of 445 patients met inclusion criteria between January and
      December 2014. The positive urine culture rate was 20%, and the rate of bladder
      debris was 22%. The mean age for those with and without bladder debris was 6.6
      and 5.5 years, respectively (p = 0.02). 23% of girls had bladder debris, compared
      to 12% of boys (p = 0.04, see results table). The sensitivity and specificity for
      bladder debris in detecting positive urine cultures was 52% and 86%,
      respectively. Forty-seven percent of those with bladder debris had positive
      cultures, compared with 12% of those without debris (p < 0.01). The relative risk
      of positive urine culture if debris is present is 3.90 (95% CI 2.73-5.55).
      Hydronephrosis or vesicoureteral reflux did not affect the relationship between
      bladder debris and positive urine cultures. CONCLUSIONS: Nearly half of pediatric
      patients undergoing urological evaluation found to have bladder debris on
      ultrasound will have a positive urine culture. Debris is noted more commonly in
      girls and at a slightly higher age. The presence of debris is associated with a
      fourfold increase in detecting a positive urine culture, regardless of debris
      severity, hydronephrosis, or vesicoureteral reflux. Given this, it is of value to
      routinely document and look for the presence of any amount of bladder debris seen
      on ultrasound, as this finding can be used to augment clinical decision-making
      and warrants strong consideration for obtaining urine culture.

PMID- 29456121
TI  - Establishment of colonic dialysis model in uremic rats by right nephrectomy and
      left partial nephrectomy.
AB  - BACKGROUND: Conventional treatments for patients suffering with end-stage renal
      disease (ESRD) has several disadvantages, highlighting the importance of other
      reproducible modalities such as colonic dialysis (CD). OBJECTIVES: The aim was to
      establish a CD model in uremic rats and evaluate the effect of two different
      peritoneal dialysis (PD) solutions. METHODS: Thirty-two male Wistar rats were
      randomly divided into four groups. After right nephrectomy and left partial
      nephrectomy, a Malone antegrade continence enema (MACE) stoma was created. Seven
      days after the procedure, blood sampling was performed. In group I (N = 8) no
      postoperative intervention was performed. In group II (N = 8), CD was started
      through the MACE stoma by a low osmolar PD solution. Rats of group III (N = 8)
      underwent the same procedure with a high osmolar PD solution. Rats of group IV (N
      = 8) underwent CD without nephrectomy in order to evaluate the feasibility of
      this technique. Mannitol and activated charcoal were also added to both PD
      solutions. Weekly blood sampling was performed in order to evaluate the plasma
      creatinine and blood urea nitrogen (BUN) level. RESULTS: In rats of the control
      group, the respective mean +/- SD creatinine level was 1.5 +/- 0.04 mg/dL, 7 days
      after the surgical procedure, but a lower creatinine level was found in groups II
      and III (0.8 +/- 0.02 and 0.5 +/- 0.03, respectively). Despite the fact that the
      creatinine level was in steady low states after regular CD in group II (1 +/-
      0.05) and group III (0.6 +/- 0.02), it remained at higher levels in the control
      group (1.7 +/- 0.08) 2 weeks postoperatively. Rats of group I did not survive
      until the third postoperative week, while the creatinine level was still lower in
      group III than in group II (0.6 +/- 0.02 vs. 1.1 +/- 0.03). Similar results were
      obtained for the BUN level at these timepoints. The mean +/- SD survival period
      was 11 +/- 2, 20 +/- 3, and 33 +/- 2 days in the animals of groups I, II, and
      III, respectively. DISCUSSION: To the best of our knowledge, this is the first
      study of CD establishment in a rat model. Unfortunately, the amount of protein
      loss, elevation of blood glucose levels, and electrolyte disturbance were not
      evaluated in the current study because of the limited amount of blood samples.
      Disturbance of these factors might be a cause of mortality in experimental groups
      undergoing CD while a significant decrease in BUN and creatinine levels was
      obtained. CONCLUSION: CD with an efficient PD solution through a MACE stoma may
      be a valuable option when conventional methods are not available.

PMID- 29456122
TI  - Blood perfusion in left inferior and middle frontal gyrus predicts communication
      skills in schizophrenia.
AB  - Schizophrenia is one of the most debilitating mental disorders, severely
      affecting patients' community functioning. Functional capacity (FC) describes the
      skills necessary for successful functional outcome (FO), such as financial
      knowledge or communication skills. We investigated whether resting-state cerebral
      blood flow (rCBF) measured at baseline with arterial spin labeling (ASL) would
      predict FC or FO at a 6-months follow-up in 27 schizophrenia patients. A negative
      linear association was noted between FC and rCBF in the left inferior and middle
      frontal gyrus, areas involved in language processing, suggesting a potential
      relationship between cerebral perfusion and prospective FC in schizophrenia.

PMID- 29456123
TI  - Activated carbon enhanced anaerobic digestion of food waste - Laboratory-scale
      and Pilot-scale operation.
AB  - Effects of activated carbon (AC) supplementation on anaerobic digestion (AD) of
      food waste were elucidated in lab- and pilot-scales. Lab-scale AD was performed
      in 1 L and 8 L digesters, while pilot-scale AD was conducted in a 1000 L
      digester. Based on the optimal dose of 15 g AC per working volume derived from
      the 1 L digester, for the same AC dosage in the 8 L digester, an improved
      operation stability coupled with a higher methane yield was achieved even when
      digesters without AC supplementation failed after 59 days due to accumulation of
      substantial organic intermediates. At the same time, color removal from the
      liquid phase of the digestate was dramatically enhanced and the particle size of
      the digestate solids was increased by 53% through AC supplementation after
      running for 59 days. Pyrosequencing of 16S rRNA gene showed the abundance of
      predominant phyla Firmicutes, Elusimicrobia and Proteobacteria selectively
      enhanced by 1.7-fold, 2.9-fold and 2.1-fold, respectively. Pilot-scale digester
      without AC gave an average methane yield of 0.466 L?(gVS)-1?d-1 at a composition
      of 53-61% v/v methane. With AC augmentation, an increase of 41% in methane yield
      was achieved in the 1000 L digester under optimal organic loading rate (1.6 g
      VSFW.L-1.d-1).

PMID- 29456125
TI  - Development and Validation of a Tool to Measure Dietitians' Self-Efficacy with
      Using Mobile Health Apps in Dietetic Practice.
AB  - OBJECTIVE: To develop and validate a tool for assessing dietitians' self-efficacy
      with using mobile health (mHealth) apps in dietetic practice. DESIGN AND
      PARTICIPANTS: A tool for measuring mHealth app self-efficacy among dietitians was
      constructed based on a literature review, consultation with experts, and
      Bandura's self-efficacy scales development guide. Senior dietetic students and
      new graduate dietitians in Australia (n = 100) tested the tool. OUTCOME MEASURES
      AND ANALYSIS: Validation of the tool was conducted using factor analysis.
      Reliability testing was undertaken to examine internal consistency and
      repeatability. RESULTS: Construct validity was demonstrated through extraction of
      4 factors with significant loadings accounting for 68% of variance: efficiency
      and effectiveness of nutrition care, training and support, integration into
      dietetic work systems, and familiarity with apps. Internal consistency
      reliability overall was 0.90; 3 of 4 constructs had Cronbach alpha > .70.
      Weighted kappas for test-retest reliability indicated moderate to substantial
      agreement (0.43-0.76). CONCLUSIONS AND IMPLICATIONS: This tool will be useful to
      researchers and dietetic associations interested in measuring dietitians' levels
      of mHealth app self-efficacy, developing interventions to enhance self-efficacy,
      and/or evaluating changes in self-efficacy after professional training. Testing
      of the tool in a more diverse sample of dietitians and among other health
      professional groups could enhance the applicability of the tool.

PMID- 29456124
TI  - A multicenter study of total pancreatectomy with islet autotransplantation
      (TPIAT): POST (Prospective Observational Study of TPIAT).
AB  - BACKGROUND/OBJECTIVES: Total pancreatectomy with islet autotransplantation
      (TPIAT) is considered for managing chronic pancreatitis in selected patients when
      medical and endoscopic interventions have not provided adequate relief from
      debilitating pain. Although more centers are performing TPIAT, we lack large,
      multi-center studies to guide decisions about selecting candidates for and timing
      of TPIAT. METHODS: Multiple centers across the United States (9 to date)
      performing TPIAT are prospectively enrolling patients undergoing TPIAT for
      chronic pancreatitis into the Prospective Observational Study of TPIAT (POST), a
      NIDDK funded study with a goal of accruing 450 TPIAT recipients. Baseline data
      include participant phenotype, pancreatitis history, and medical/psychological
      comorbidities from medical records, participant interview, and participant self
      report (Medical Outcomes Survey Short Form-12, EQ-5D, andPROMIS inventories for
      pain interference, depression, and anxiety). Outcome measures are collected to at
      least 1 year after TPIAT, including the same participant questionnaires, visual
      analog pain scale, pain interference scores, opioid requirements, insulin
      requirements, islet graft function, and hemoglobin A1c. Health resource
      utilization data are collected for a cost-effectiveness analysis. Biorepository
      specimens including urine, serum/plasma, genetic material (saliva and blood), and
      pancreas tissue are collected for future study. CONCLUSIONS: This ongoing
      multicenter research study will enroll and follow TPIAT recipients, aiming to
      evaluate patient selection and timing for TPIAT to optimize pain relief, quality
      of life, and diabetes outcomes, and to measure the procedure's cost
      effectiveness. A biorepository is also established for future ancillary studies.

PMID- 29456126
TI  - Body Quest Parent: A Text Message Parent Education Intervention to Supplement a
      School-Based Obesity Prevention Initiative for Third-Graders.

PMID- 29456127
TI  - Neurocognitive disorder in hypertensive patients. Heart-Brain Study.
AB  - The relation between hypertension and cognitive impairment is an undisputable
      fact. The aims of this study were to determine the prevalence of cognitive
      impairment in hypertensive patients, to identify the most affected cognitive
      domain, and to observe the association with different parameters of hypertension
      and other vascular risk factors. A multicentre study was carried out, and 1281
      hypertensive patients of both genders and >=21 years of age were included. Data
      on the following parameters were obtained: cognitive status (Minimal Cognitive
      Examination), behavioural status (Hospital Anxiety and Depression Scale), blood
      pressure, anthropometry, and biochemical profile. The average age was 60.2+/-13.5
      years (71% female), and the educational level was 9.9+/-5.1 years. Global
      cognitive impairment was seen in 22.1%, executive dysfunction in 36.2%, and
      semantic memory impairment in 48.9%. Cognitive impairment was higher in males
      (36.8% vs. 30.06%) within both the 70-79-year-old and the >=80-year-old (50% vs.
      40%) age groups. Abnormal Clock Drawing Test results were related to high pulse
      pressure (p<0.0036), and abnormal Mini-Boston Naming Test results to both high
      systolic blood pressure (p<0.052) and pulse pressure (p<0.001). The
      treated/uncontrolled hypertensive group showed abnormal results both in the Mini
      Mental State Examination (OR, 0.73; p=0.036) and the Mini-Boston Naming Test (OR,
      1.36; p=0.021). Among patients without cognitive impairment (MMSE >24), 29.4%
      presented executive dysfunction, and 41.5% semantic memory impairment. Cognitive
      impairment was higher in hypertensive patients than in the general population.
      Executive functions and semantic memory were the most affected cognitive domains.
      High systolic blood pressure and pulse pressure were associated with abnormal
      results in cognitive tests.

PMID- 29456129
TI  - Multi-elemental ionic liquid-based solvent bar micro-extraction of priority and
      emerging trace metallic pollutants (Cd, Ag, Pd) in natural waters.
AB  - Transition metals Cd, Pd and Ag are toxic even at very low concentration. Cd is
      considered a priority substance; while, Pd and Ag are emerging pollutants.
      Membrane technologies have been applied for their extraction; however, they
      require important amounts of reagents, time and energy. Additionally, effective
      reagents for metal extraction in saline natural waters are limited. In this case,
      hollow fiber liquid phase micro-extraction with a configuration of solvent bar
      (SBME) using the ionic liquid Cyphos(r) 101 as extractant is proposed. Optimized
      conditions for SBME of Cd, Ag and Pd were 50% Cyphos(r) 101 in the organic
      solution, extraction time 30 min and 800 rpm stirring rate. Leaching was in all
      cases lower than 0.1%. Metallic concentrations were measured by flame atomic
      absorption spectroscopy. The method was applied to the extraction of Ag, Cd and
      Pd in natural water samples. Except for waste water, Pd extraction was higher
      than 90% in all cases. Cd (~100%) and Ag (93-95%) offered their best results for
      saline samples. Concluding, the proposed system is a low cost and green
      methodology that allows a simple and fast extraction of trace pollutants such as
      Ag, Cd and Pd in different natural waters, including highly saline samples.

PMID- 29456128
TI  - Transcranial direct current stimulation and constraint-induced therapy in
      cerebral palsy: A randomized, blinded, sham-controlled clinical trial.
AB  - : We investigated the safety, feasibility, and efficacy of transcranial direct
      current stimulation (tDCS) combined with constraint-induced movement therapy
      (CIMT) in children and young adults with unilateral cerebral palsy. Twenty
      participants were randomized to receive active or sham tDCS. The intervention
      consisted of 10 consecutive weekday sessions of tDCS applied to the non-lesioned
      hemisphere (20 min) concurrently with CIMT (120 min). Participants, caregivers,
      and interventionists were blinded to group assignment. The primary safety outcome
      investigated adverse events. The primary behavioral outcome was the Assisting
      Hand Assessment. All 20 participants (mean age = 12.7 yrs, range = 7.4-21.6
      years) were evaluated for the primary outcomes. No serious adverse events
      occurred, and the most commonly reported minor adverse events were headache and
      itchiness. Both groups demonstrated a significant improvement in hand function
      after the intervention, although no significant effect of tDCS was observed
      (between-group difference = -2.18, 95% CI = [-6.48, 2.12], p = 0.30). Although
      hand function improved overall, no significant differences between intervention
      groups were found. Children with preserved corticospinal tract circuitry from the
      lesioned hemisphere, compared to those without, showed greater improvement in
      hand function (mean difference = 3.04, 95% CI = [-0.64, 6.72], p = 0.099). Our
      study demonstrates the safety and feasibility of serial sessions of tDCS, and
      presents preliminary evidence for the effect of CST circuitry on outcomes
      following tDCS/CIMT. Future work in children with unilateral cerebral palsy
      should focus on the optimal dosing and consider individual brain circuitry when
      describing response to combined interventions. CLINICAL TRIALS REGISTRATION:
      Clinicaltrials.govNCT 02250092.

PMID- 29456130
TI  - Increments in serum high-density lipoprotein cholesterol over time are not
      associated with improved outcomes in incident hemodialysis patients.
AB  - BACKGROUND: Elevated serum high-density lipoprotein cholesterol (HDL-C) has not
      been associated with better cardiovascular (CV) and all-cause mortality in
      hemodialysis patients. However, the association between change in HDL over time
      and mortality has not been fully examined. OBJECTIVE: In a nationally
      representative cohort of incident hemodialysis patients who had available HDL
      data at baseline and 6 months after dialysis initiation, we studied the
      association of change in HDL-C during the first 6 months of dialysis with all
      cause and CV mortality. METHODS: Associations between HDL-C change and mortality
      were determined in Cox proportional hazard regression models with adjustment for
      multiple variables. RESULTS: In case-mix models, there was a J-shaped association
      between change in HDL-C and mortality, such that quartiles 1 (<-5 mg/dL) and 4
      (>=7 mg/dL) were each associated with higher all-cause (hazard ratio, 1.32 [95%
      confidence interval, 1.21-1.45] and 1.09 [1.01-1.18]) and CV (1.28 [1.06-1.55]
      and 1.23 [1.04-1.45]) death risk, respectively. In fully adjusted models that
      included indices of malnutrition and inflammation, the higher death risk observed
      in the lowest quartile was attenuated, whereas the highest quartile continued to
      demonstrate significantly higher all-cause (1.11 [1.02-1.20]) and CV mortality
      (1.15 [1.00-1.32]). These associations persisted across various subgroups.
      CONCLUSIONS: Although malnutrition and inflammation may explain the increased
      risk for mortality in patients with decreasing serum HDL-C concentrations over
      time, these indices do not mitigate the elevated risk in patients with rising
      serum HDL-C. We found that increasing serum HDL-C over time is paradoxically
      associated with worse outcomes in incident hemodialysis patients.

PMID- 29456131
TI  - High expression of CC chemokine receptor 5 (CCR5) promotes disease progression in
      patients with B-cell non-Hodgkin lymphomas.
AB  - Chemokines are small proteins, that regulate cell migration in many physiological
      and pathologic processes in human body. They are also responsible for cancer
      progression. CC chemokine receptor 5 (CCR5) is responsible for cell recruitment
      in inflammation and may be involved in antitumor immune response controlling.
      Aberrant CCR5 can be found in different kind of cancers, not only hematological,
      but also solid tumors. Non-Hodgkin lymphomas consist of many lymphoma subtypes.
      They predominantly derive from B cells and can have very heterogenous clinical
      course. That is why new prognostic factors are still needed to predict and select
      high-risk patients. We evaluated CCR5 expression in lymph nodes derived from B
      cell lymphomas in comparison to reactive lymphatic tissue (reactive lymph nodes):
      samples of lymphoma lymph nodes, peripheral blood, and bone marrow aspirates of
      patients with B-cell non-Hodgkin lymphoma were taken at diagnosis and after
      completed chemotherapy. Gene expression was determined by the reverse
      transcription-polymerase chain reaction method. Expression was estimated from 0AU
      (no amplificate signal) to 3AU (maximal amplificate signal). We found low CCR5
      expression in lymphomas and reactive lymph nodes. Higher CCR5 gene expression in
      lymphoma patients was correlated with advanced stage of the disease, high
      proliferation index (Ki-67), and international prognostic index. Patients with
      higher CCR5 expression had shorter survival. CCR5 high expression may have a role
      in non-Hodgkin's lymphomas progression and can influence patients' survival. CCR5
      also can become an immunotherapeutic target for novel treatment options in the
      future as well as new prognostic factor.

PMID- 29456132
TI  - CSF lamp2 concentrations are decreased in female Parkinson's disease patients
      with LRRK2 mutations.
AB  - Lysosome-associated membrane glycoprotein 2 (lamp2) plays critical roles in
      chaperone-mediated autophagy (CMA) and macroautophagy. Its isoform lamp2a is
      decreased in Parkinson's disease (PD) substantia nigra. Mutations in the leucine
      rich repeat kinase 2 (LRRK2) gene are the most known common cause of late-onset
      PD; although LRRK2 is thought to regulate macroautophagy, the influence of LRRK2
      mutations on lamp2 concentrations in the CNS is unknown. To examine this issue we
      compared lamp2 levels in cerebrospinal fluid (CSF) between sporadic PD (sPD)
      patients (n = 31), LRRK2 PD patients (n = 20), and healthy control subjects with
      or without LRRK2 mutations (LRRK2 CTL = 30, CTL = 27). We also examined lamp2's
      correlations with age, oxidative stress, PD progression, and PD duration. Median
      lamp2 concentrations (pg/mL) were LRRK2 PD = 127, sPD = 333, CTL = 436, and LRRK2
      CTL = 412. Log-transformed lamp2 concentrations, adjusting for gender effects
      (and excluding male LRRK2 PD patients because of low number), were lower in
      female LRRK2 PD patients than in LRRK2 CTL (p = 0.002) and CTL (p = 0.005)
      subjects (p = 0.06 for lamp2 comparison between female LRRK2 PD patients and sPD
      patients). Lamp2 did not appear to be associated with age, PD progression, or PD
      duration; however, three of four Spearman rho values for correlations between
      lamp2 and oxidative stress markers in PD subjects were >=0.30. These findings
      suggest that CSF lamp2 concentrations may be decreased in female LRRK2 PD
      patients compared to healthy individuals with or without LRRK2 mutations.

PMID- 29456133
TI  - No evidence for systematic white matter correlates of dyslexia: An Activation
      Likelihood Estimation meta-analysis.
AB  - Dyslexia is a prevalent neurodevelopmental disorder, characterized by reading and
      spelling difficulties. Beyond the behavioral and functional correlates of this
      condition, a growing number of studies have explored structural differences
      between individuals with dyslexia and typically developing individuals. To date,
      findings remain disparate - some studies suggest differences in fractional
      anisotropy (FA), an indirect measure of white matter integrity, whereas others do
      not identify significant disparities. Here, we synthesized the existing
      literature on this topic by conducting a meta-analysis of Diffusion Tensor
      Imaging (DTI) studies investigating white matter correlates of dyslexia via voxel
      based analyses (VBA) of FA. Our results showed no reliable clusters underlying
      differences between dyslexics and typical individuals, after correcting for
      multiple comparisons (false discovery rate correction). Because group comparisons
      might be too coarse to yield subtle differences, we further explored differences
      in FA as a function of reading ability, measured on a continuous scale.
      Consistent with our initial findings, reading ability was not associated with
      reliable differences in white matter integrity. These findings nuance the current
      view of profound, structural differences underlying reading ability and its
      associated disorders, and suggest that their neural correlates might be more
      subtle than previously thought.

PMID- 29456134
TI  - Parietal control network activation during memory tasks may be associated with
      the co-occurrence of externally and internally directed cognition: A cross
      function meta-analysis.
AB  - Functional neuroimaging studies on episodic memory retrieval consistently
      indicated the activation of the precuneus (PCU), mid-cingulate cortex (MCC), and
      lateral intraparietal sulcus (latIPS) regions. Although studies typically
      interpreted these activations in terms of memory retrieval processes, resting
      state functional connectivity data indicate that these regions are part of the
      frontoparietal control network, suggesting a more general, cross-functional role.
      In this regard, this study proposes a novel hypothesis which suggests that the
      parietal control network plays a strong role in accommodating the co-occurrence
      of externally directed cognition (EDC) and internally directed cognition (IDC),
      which are typically antagonistic to each other. To evaluate how well this dual
      cognitive processes hypothesis can account for parietal activation patterns
      during memory tasks, this study provides a cross-function meta-analysis involving
      3 different memory paradigms, namely, retrieval success (hit > correct
      rejection), repetition enhancement (repeated > novel), and subsequent forgetting
      (forgotten > remembered). Common to these paradigms is that the target condition
      may involve both EDC (stimulus processing and motor responding) and IDC
      (intentional remembering, involuntary awareness of previous encounter, or task
      unrelated thoughts) strongly, whereas the reference condition may involve EDC to
      a greater extent, but IDC to a lesser extent. Thus, the dual cognitive processes
      hypothesis predicts that each of these paradigms will activate similar,
      overlapping PCU, MCC, and latIPS regions. The results were fully consistent with
      the prediction, supporting the dual cognitive processes hypothesis. Evidence from
      relevant prior studies suggests that the dual cognitive processes hypothesis may
      also apply to non-memory domain tasks.

PMID- 29456135
TI  - Pericyte ALK5/TIMP3 Axis Contributes to Endothelial Morphogenesis in the
      Developing Brain.
AB  - The murine embryonic blood-brain barrier (BBB) consists of endothelial cells
      (ECs), pericytes (PCs), and basement membrane. Although PCs are critical for
      inducing vascular stability, signaling pathways in PCs that regulate EC
      morphogenesis during BBB development remain unexplored. Herein, we find that
      murine embryos lacking the transforming growth factor beta (TGF-beta) receptor
      activin receptor-like kinase 5 (Alk5) in brain PCs (mutants) develop gross
      germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH). The germinal
      matrix (GM) is a highly vascularized structure rich in neuronal and glial
      precursors. We show that GM microvessels of mutants display abnormal dilation,
      reduced PC coverage, EC hyperproliferation, reduced basement membrane collagen,
      and enhanced perivascular matrix metalloproteinase activity. Furthermore, ALK5
      depleted PCs downregulate tissue inhibitor of matrix metalloproteinase 3 (TIMP3),
      and TIMP3 administration to mutants improves endothelial morphogenesis and
      attenuates GMH-IVH. Overall, our findings reveal a key role for PC ALK5 in
      regulating brain endothelial morphogenesis and a substantial therapeutic
      potential for TIMP3 during GMH-IVH.

PMID- 29456136
TI  - A Sex Chromosome piRNA Promotes Robust Dosage Compensation and Sex Determination
      in C. elegans.
AB  - In metazoans, Piwi-related Argonaute proteins engage piRNAs (Piwi-interacting
      small RNAs) to defend the genome against invasive nucleic acids, such as
      transposable elements. Yet many organisms-including worms and humans-express
      thousands of piRNAs that do not target transposons, suggesting that piRNA
      function extends beyond genome defense. Here, we show that the X chromosome
      derived piRNA 21ux-1 downregulates XOL-1 (XO Lethal), a master regulator of X
      chromosome dosage compensation and sex determination in Caenorhabditis elegans.
      Mutations in 21ux-1 and several Piwi-pathway components sensitize hermaphrodites
      to dosage compensation and sex determination defects. We show that the piRNA
      pathway also targets xol-1 in C. briggsae, a nematode species related to C.
      elegans. Our findings reveal physiologically important piRNA-mRNA interactions,
      raising the possibility that piRNAs function broadly to ensure robust gene
      expression and germline development.

PMID- 29456137
TI  - Lineage-Biased Hematopoietic Stem Cells Are Regulated by Distinct Niches.
AB  - The spatial localization of hematopoietic stem cells (HSCs) in the bone marrow
      (BM) remains controversial, with some studies suggesting that they are maintained
      in homogeneously distributed niches while others have suggested the contributions
      of distinct niche structures. Subsets of quiescent HSCs have been reported to
      associate with megakaryocytes (MK) or arterioles in the BM. However, these HSC
      subsets have not been prospectively defined. Here, we show that platelet and
      myeloid-biased HSCs, marked by von Willebrand factor (vWF) expression, are highly
      enriched in MK niches. Depletion of MK selectively expands vWF+ HSCs, whereas the
      depletion of NG2+ arteriolar niche cells selectively depletes vWF- lymphoid
      biased HSCs. In addition, MK depletion compromises vWF+ HSC function by reducing
      their long-term self-renewal capacity and eliminating their lineage bias after
      transplantation. These studies demonstrate the existence of two spatially and
      functionally separate BM niches for HSC subsets with distinct developmental
      potential.

PMID- 29456138
TI  - The InR/Akt/TORC1 Growth-Promoting Signaling Negatively Regulates JAK/STAT
      Activity and Migratory Cell Fate during Morphogenesis.
AB  - Cell growth and cell differentiation are two distinct yet coupled developmental
      processes, but how they are coordinated is not well understood. During Drosophila
      oogenesis, we found that the growth-promoting InR/Akt/TOR pathway was involved in
      suppressing the fate determination of the migratory border cells. The InR/Akt/TOR
      pathway signals through TOR and Raptor, components of TORC1, to downregulate the
      JAK/STAT pathway, which is necessary and sufficient for border cell fate
      determination. TORC1 promotes the protein stability of SOCS36E, the conserved
      negative regulator of JAK/STAT signaling, through physical interaction,
      suggesting that TORC1 acts as a key regulator coordinating both cell growth and
      cell differentiation.

PMID- 29456139
TI  - Selective Attention Gates the Interactive Crossmodal Coupling between Perceptual
      Systems.
AB  - Sensory cortical systems often activate in parallel, even when stimulation is
      experienced through a single sensory modality [1-3]. Co-activations may reflect
      the interactive coupling between information-linked cortical systems or merely
      parallel but independent sensory processing. We report causal evidence consistent
      with the hypothesis that human somatosensory cortex (S1), which co-activates with
      auditory cortex during the processing of vibrations and textures [4-9],
      interactively couples to cortical systems that support auditory perception. In a
      series of behavioral experiments, we used transcranial magnetic stimulation (TMS)
      to probe interactions between the somatosensory and auditory perceptual systems
      as we manipulated attention state. Acute TMS over S1 impairs auditory frequency
      perception when subjects simultaneously attend to auditory and tactile frequency,
      but not when attention is directed to audition alone. Auditory frequency
      perception is unaffected by TMS over visual cortex, thus confirming the
      privileged interactions between the somatosensory and auditory systems in
      temporal frequency processing [10-13]. Our results provide a key demonstration
      that selective attention can modulate the functional properties of cortical
      systems thought to support specific sensory modalities. The gating of crossmodal
      coupling by selective attention may critically support multisensory interactions
      and feature-specific perception.

PMID- 29456140
TI  - Visual Selective Attention in Mice.
AB  - Visual selective attention is a fundamental cognitive ability that allows us to
      process relevant visual stimuli while ignoring irrelevant distracters and has
      been extensively studied in human and non-human primate subjects. Mice have
      emerged as a powerful animal model for studying aspects of the visual system but
      have not yet been shown to exhibit visual selective attention. Differences in the
      organization of the visual systems of primates and mice raise the possibility
      that selective visual attention might not be present in mice, at least not in the
      forms that are well established in primates. Here, we tested for selective visual
      attention in mice by using three behavioral paradigms adapted from classic
      studies of attention. In a Posner-style cueing task, a spatial cue indicated the
      probable location of the relevant visual event, and we found that accuracy was
      higher and reaction times were shorter on validly cued trials. In a cue versus no
      cue task, an informative spatial cue was provided on half the trials, and mice
      had higher accuracy and shorter reaction times with spatial cues and also lower
      detection thresholds measured from psychometric curves. In a filter task, the
      spatial cue indicated the location of the relevant visual event, and we found
      that mice could be trained to ignore irrelevant but otherwise identical visual
      events at uncued locations. Together, these results demonstrate that mice exhibit
      visual selective attention, paving the way to use classic attention paradigms in
      mice to study the genetic and neuronal circuit mechanisms of selective attention.

PMID- 29456141
TI  - Inhomogeneous Encoding of the Visual Field in the Mouse Retina.
AB  - Stimulus characteristics of the mouse's visual field differ above and below the
      skyline. Here, we show for the first time that retinal ganglion cells (RGCs), the
      output neurons of the retina, gradually change their functional properties along
      the ventral-dorsal axis to allow better representation of the different stimulus
      characteristics. We conducted two-photon targeted recordings of transient
      Offalpha-RGCs and found that they gradually became more sustained along the
      ventral-dorsal axis, revealing >5-fold-longer duration responses in the dorsal
      retina. Using voltage-clamp recordings, pharmacology, and genetic manipulation,
      we demonstrated that the primary rod pathway underlies this variance. Our
      findings challenge the current belief that RGCs of the same subtype exhibit the
      same light responses, regardless of retinal location, and suggest that networks
      underlying RGC responses may change with retinal location to enable optimized
      sampling of the visual image.

PMID- 29456143
TI  - Neocortical Association Cell Types in the Forebrain of Birds and Alligators.
AB  - The avian dorsal telencephalon has two vast territories, the nidopallium and the
      mesopallium, both of which have been shown to contribute substantially to higher
      cognitive functions. From their connections, these territories have been proposed
      as equivalent to mammalian neocortical layers 2 and 3, various neocortical
      association areas, or the amygdala, but whether these are analogies or homologies
      by descent is unknown. We investigated the molecular profiles of the mesopallium
      and the nidopallium with RNA-seq. Gene expression experiments established that
      the mesopallium, but not the nidopallium, shares a transcription factor network
      with the intratelencephalic class of neocortical neurons, which are found in
      neocortical layers 2, 3, 5, and 6. Experiments in alligators demonstrated that
      these neurons are also abundant in the crocodilian cortex and form a large
      mesopallium-like structure in the dorsal ventricular ridge. Together with
      previous work, these molecular findings indicate a homology by descent for
      neuronal cell types of the avian dorsal telencephalon with the major excitatory
      cell types of mammalian neocortical circuits: the layer 4 input neurons, the deep
      layer output neurons, and the multi-layer intratelencephalic association neurons.
      These data raise the interesting possibility that avian and primate lineages
      evolved higher cognitive abilities independently through parallel expansions of
      homologous cell populations.

PMID- 29456142
TI  - The FERONIA Receptor Kinase Maintains Cell-Wall Integrity during Salt Stress
      through Ca2+ Signaling.
AB  - Cells maintain integrity despite changes in their mechanical properties elicited
      during growth and environmental stress. How cells sense their physical state and
      compensate for cell-wall damage is poorly understood, particularly in plants.
      Here we report that FERONIA (FER), a plasma-membrane-localized receptor kinase
      from Arabidopsis, is necessary for the recovery of root growth after exposure to
      high salinity, a widespread soil stress. The extracellular domain of FER displays
      tandem regions of homology with malectin, an animal protein known to bind di
      glucose in vitro and important for protein quality control in the endoplasmic
      reticulum. The presence of malectin-like domains in FER and related receptor
      kinases has led to widespread speculation that they interact with cell-wall
      polysaccharides and can potentially serve a wall-sensing function. Results
      reported here show that salinity causes softening of the cell wall and that FER
      is necessary to sense these defects. When this function is disrupted in the fer
      mutant, root cells explode dramatically during growth recovery. Similar defects
      are observed in the mur1 mutant, which disrupts pectin cross-linking.
      Furthermore, fer cell-wall integrity defects can be rescued by treatment with
      calcium and borate, which also facilitate pectin cross-linking. Sensing of these
      salinity-induced wall defects might therefore be a direct consequence of physical
      interaction between the extracellular domain of FER and pectin. FER-dependent
      signaling elicits cell-specific calcium transients that maintain cell-wall
      integrity during salt stress. These results reveal a novel extracellular toxicity
      of salinity, and identify FER as a sensor of damage to the pectin-associated
      wall.

PMID- 29456145
TI  - The Interrelationships of Land Plants and the Nature of the Ancestral
      Embryophyte.
AB  - The evolutionary emergence of land plant body plans transformed the planet.
      However, our understanding of this formative episode is mired in the uncertainty
      associated with the phylogenetic relationships among bryophytes (hornworts,
      liverworts, and mosses) and tracheophytes (vascular plants). Here we attempt to
      clarify this problem by analyzing a large transcriptomic dataset with models that
      allow for compositional heterogeneity between sites. Zygnematophyceae is resolved
      as sister to land plants, but we obtain several distinct relationships between
      bryophytes and tracheophytes. Concatenated sequence analyses that can explicitly
      accommodate site-specific compositional heterogeneity give more support for a
      mosses-liverworts clade, "Setaphyta," as the sister to all other land plants, and
      weak support for hornworts as the sister to all other land plants. Bryophyte
      monophyly is supported by gene concatenation analyses using models explicitly
      accommodating lineage-specific compositional heterogeneity and analyses of gene
      trees. Both maximum-likelihood analyses that compare the fit of each gene tree to
      proposed species trees and Bayesian supertree estimation based on gene trees
      support bryophyte monophyly. Of the 15 distinct rooted relationships for
      embryophytes, we reject all but three hypotheses, which differ only in the
      position of hornworts. Our results imply that the ancestral embryophyte was more
      complex than has been envisaged based on topologies recognizing liverworts as the
      sister lineage to all other embryophytes. This requires many phenotypic character
      losses and transformations in the liverwort lineage, diminishes inconsistency
      between phylogeny and the fossil record, and prompts re-evaluation of the
      phylogenetic affinity of early land plant fossils, the majority of which are
      considered stem tracheophytes.

PMID- 29456144
TI  - Global Demand for Natural Resources Eliminated More Than 100,000 Bornean
      Orangutans.
AB  - Unsustainable exploitation of natural resources is increasingly affecting the
      highly biodiverse tropics [1, 2]. Although rapid developments in remote sensing
      technology have permitted more precise estimates of land-cover change over large
      spatial scales [3-5], our knowledge about the effects of these changes on
      wildlife is much more sparse [6, 7]. Here we use field survey data, predictive
      density distribution modeling, and remote sensing to investigate the impact of
      resource use and land-use changes on the density distribution of Bornean
      orangutans (Pongo pygmaeus). Our models indicate that between 1999 and 2015, half
      of the orangutan population was affected by logging, deforestation, or
      industrialized plantations. Although land clearance caused the most dramatic
      rates of decline, it accounted for only a small proportion of the total loss. A
      much larger number of orangutans were lost in selectively logged and primary
      forests, where rates of decline were less precipitous, but where far more
      orangutans are found. This suggests that further drivers, independent of land-use
      change, contribute to orangutan loss. This finding is consistent with studies
      reporting hunting as a major cause in orangutan decline [8-10]. Our predictions
      of orangutan abundance loss across Borneo suggest that the population decreased
      by more than 100,000 individuals, corroborating recent estimates of decline [11].
      Practical solutions to prevent future orangutan decline can only be realized by
      addressing its complex causes in a holistic manner across political and societal
      sectors, such as in land-use planning, resource exploitation, infrastructure
      development, and education, and by increasing long-term sustainability [12].
      VIDEO ABSTRACT.

PMID- 29456146
TI  - A Comprehensive and Dated Phylogenomic Analysis of Butterflies.
AB  - Butterflies (Papilionoidea), with over 18,000 described species [1], have
      captivated naturalists and scientists for centuries. They play a central role in
      the study of speciation, community ecology, biogeography, climate change, and
      plant-insect interactions and include many model organisms and pest species [2,
      3]. However, a robust higher-level phylogenetic framework is lacking. To fill
      this gap, we inferred a dated phylogeny by analyzing the first phylogenomic
      dataset, including 352 loci (> 150,000 bp) from 207 species representing 98% of
      tribes, a 35-fold increase in gene sampling and 3-fold increase in taxon sampling
      over previous studies [4]. Most data were generated with a new anchored hybrid
      enrichment (AHE) [5] gene kit (BUTTERFLY1.0) that includes both new and
      frequently used (e.g., [6]) informative loci, enabling direct comparison and
      future dataset merging with previous studies. Butterflies originated around 119
      million years ago (mya) in the late Cretaceous, but most extant lineages diverged
      after the Cretaceous-Paleogene (K-Pg) mass-extinction 65 mya. Our analyses
      support swallowtails (Papilionidae) as sister to all other butterflies, followed
      by skippers (Hesperiidae) + the nocturnal butterflies (Hedylidae) as sister to
      the remainder, indicating a secondary reversal from diurnality to nocturnality.
      The whites (Pieridae) were strongly supported as sister to brush-footed
      butterflies (Nymphalidae) and blues + metalmarks (Lycaenidae and Riodinidae). Ant
      association independently evolved once in Lycaenidae and twice in Riodinidae.
      This study overturns prior notions of the taxon's evolutionary history, as many
      long-recognized subfamilies and tribes are para- or polyphyletic. It also
      provides a much-needed backbone for a revised classification of butterflies and
      for future comparative studies including genome evolution and ecology.

PMID- 29456147
TI  - Dynamic Interplay of Value and Sensory Information in High-Speed Decision Making.
AB  - In dynamic environments, split-second sensorimotor decisions must be prioritized
      according to potential payoffs to maximize overall rewards. The impact of
      relative value on deliberative perceptual judgments has been examined extensively
      [1-6], but relatively little is known about value-biasing mechanisms in the
      common situation where physical evidence is strong but the time to act is
      severely limited. In prominent decision models, a noisy but statistically
      stationary representation of sensory evidence is integrated over time to an
      action-triggering bound, and value-biases are affected by starting the integrator
      closer to the more valuable bound. Here, we show significant departures from this
      account for humans making rapid sensory-instructed action choices. Behavior was
      best explained by a simple model in which the evidence representation-and hence,
      rate of accumulation-is itself biased by value and is non-stationary, increasing
      over the short decision time frame. Because the value bias initially dominates,
      the model uniquely predicts a dynamic "turn-around" effect on low-value cues,
      where the accumulator first launches toward the incorrect action but is then re
      routed to the correct one. This was clearly exhibited in electrophysiological
      signals reflecting motor preparation and evidence accumulation. Finally, we
      construct an extended model that implements this dynamic effect through plausible
      sensory neural response modulations and demonstrate the correspondence between
      decision signal dynamics simulated from a behavioral fit of that model and the
      empirical decision signals. Our findings suggest that value and sensory
      information can exert simultaneous and dynamically countervailing influences on
      the trajectory of the accumulation-to-bound process, driving rapid, sensory
      guided actions.

PMID- 29456149
TI  - Impact of a Universal Medication Schedule on rationalising and understanding of
      medication; a randomised controlled trial.
AB  - BACKGROUND: Patients frequently encounter difficulty understanding their
      prescription drug labels. This problem is more common in patients with limited
      health literacy (HL). Patients are not always counselled on their medicines by
      their doctor or pharmacist, therefore this label can be an important source of
      information. OBJECTIVE: To assess the impact of a Universal Medication Schedule
      (UMS) on the knowledge and consolidation of a prescription drug regimen compared
      to standard pharmacy labelling. METHODS: Seventy-six in-patients at a specialised
      rehabilitation hospital in Dublin, Ireland, were randomised into control (usual
      care) or intervention (UMS) groups. Adult in-patients, receiving oral medicines,
      who spoke English fluently were included. Patients with dexterity issues
      documented, or those unable to provide written informed consent were excluded.
      The Newest Vital Sign (NVS) and validated HL screening questions measured HL. A
      five medication regimen was presented to each participant, and they were asked
      questions to assess their understanding of the medication regimen and were asked
      to dose out the medications into a 24 h dosette box. Data analysis was conducted
      using SPSS(r) (IBM Corp.), V23. RESULTS: The majority of participants (n = 76)
      were Irish (89.5%), male (63.2%) and the median age of participants was 49 years.
      46% of participants had a third level qualification, however 14.4% of
      participants had not completed any formal school examinations. Those in the UMS
      group displayed better understanding of the prescription regimen than those in
      the usual care group, but this was not statistically significant. (Mean score
      9.28 vs 8.81, p = 0.135). Subgroup analysis did not find any additional benefit
      of UMS in those with limited health literacy (Mean score 8.56 vs 9.06, p = 0.514)
      but rather in those who said that they found instructions on tablets hard to
      understand (Mean score 10.00 vs 8.43, p = 0.019). CONCLUSION: A UMS approach may
      improve patients understanding and use of their medicines.

PMID- 29456150
TI  - Antidepressants as antipruritic agents: A review.
AB  - Pruritus is a concomitant symptom of various underlying disorders viz.
      dermatological, systemic and psychiatric disorders that provoke the person to
      scratch the skin. Many natural as well as, antipruritic therapies are usually
      practiced in the treatment of pruritus including general preventive measures,
      topical therapies such as cooling agents, antihistamines, anesthetics, capsaicin,
      corticosteroids, immunomodulators and; systemic therapies including
      administration of antihistamines, opioid antagonists/agonists, antiepileptic
      drugs/neuroleptics (e.g., gabapentin and pregabalin), antidepressants (e.g.,
      doxepin, amitriptyline, paroxetine, fluvoxamine, sertraline, escitalopram and
      mirtazapine) (Patel and Yosipovitch, 2010; Reich et al., 2011; Martin and
      Padilla, 2015; Eskeland et al., 2016). Topical therapies are the mainstay of
      treatment of delicate and localized pruritus while other systemic drug therapies
      are used to treat stern and generalized pruritus. The reported antipruritic
      activity of some antidepressant drugs has intrigued this review to focus on the
      types of pruritus, pruritus mechanism, the antipruritic mechanism of
      antidepressants and to comprehend the role of antidepressants in the management
      of pruritus.

PMID- 29456151
TI  - Erratum to "Arteriopathy after transarterial chemo-lipiodolization for
      hepatocellular carcinoma" [Diagn. Interv. Imaging 98 (12) (2017) 827-35].

PMID- 29456152
TI  - Erratum to "In vivo percutaneous microwave ablation in kidneys: Correlation with
      ex vivo data and ablation work" [Diagn. Interv. Imaging 99 (1) (2018) 3-8].

PMID- 29456153
TI  - Differences Between Patients With Sarcoidosis With and Without Joint Involvement
      Treated for Fifteen Years in a Third Level Hospital.
AB  - INTRODUCTION: Sarcoidosis is a complex disease of unknown etiology, with a
      variable course and highly different forms of presentation. Our objective was to
      characterize all our patients with sarcoidosis with emphasis on their clinical
      presentation and to establish differences between patients with sarcoidosis with
      and without joint involvement. METHODS: We reviewed the medical records of all
      patients with a diagnosis of sarcoidosis who were treated at the outpatient or
      inpatient services of the Pablo Tobon Uribe Hospital in Medellin, Colombia, from
      January 2002 to April 2017. RESULTS: We identified 22 patients with sarcoidosis.
      There were joint symptoms in 13 of them. All but one of the patients with
      sarcoidosis affecting the joints had concomitant skin involvement (92%), which
      was much less frequent in patients without joint involvement (22%) (odds
      ratio=4.2; P<.001). CONCLUSIONS: Patients with sarcoidosis who have joint
      involvement have a much higher frequency of concomitant skin involvement. The
      absence of cutaneous findings in a patient with joint symptoms decreases the
      likelihood of sarcoidosis.

PMID- 29456154
TI  - Diagnosis of Osteochondromatosis as an Incidental Finding in Revision Surgery
      After Failed Intramedullary Nailing of the Hip.

PMID- 29456155
TI  - Rheumatic Syndromes and Occult Tumor: 10-year Experience in a Teaching Hospital.
AB  - OBJECTIVE: To describe the different clinical characteristics of patients
      admitted to the Rheumatology Department due to rheumatic manifestations as the
      first expression of an unknown malignant process. PATIENTS AND METHODS:
      Retrospective and descriptive observational study involving the review of the
      medical records of those admitted to rheumatology in the University Hospital of
      Ciudad Real between January 2007 and August 2017 for initial rheumatic
      manifestations with a suspicion at discharge of an unknown tumor. RESULTS: In
      all, 64 patients were identified from more than 500 admissions. The most common
      rheumatic manifestations were inflammatory low back pain, polyarthralgia, hip
      pain, thoracic spine pain, cervical pain, polyarthritis and polymyalgia
      rheumatica. Forty-four percent had low hemoglobin, 70% had elevation of acute
      phase reactants, 62% had abnormal tumor markers, 76% had metastatic lesions. In
      20% the primary tumor was of pulmonary origin and only 26.56% received palliative
      treatment; 64% died. DISCUSSION: It is important to consider the possibility of
      an underlying malignant process in the differential diagnosis since its early
      identification can be determinant for prognosis.

PMID- 29456156
TI  - A multilayer coil in type-I counter-current chromatography.
AB  - In the present study, a novel model of type-I counter-current chromatography was
      developed to simplify the separation column manufacture and extend its
      application ranges. In this system, a multilayer coil was used as the separation
      column of type-I counter-current chromatography for the first time. The
      chromatographic performance of this apparatus was evaluated in terms of retention
      of the stationary phase (Sf), theoretical plate (N) and peak resolution (Rs)
      using dipeptides and DNP-amino acids as test samples with two classic solvent
      systems composed of 1-butanol-acetic acid-water (4:1:5, v/v) (BAW) and hexane
      ethyl acetate-methanol-0.1 M HCl (1:1:1:1, v/v) (HEMW), respectively. The results
      indicated that the performance was optimal at the revolution speed of 200 rpm.
      The lower flow rate was more beneficial to retention of stationary phase and peak
      resolution. Over all results of our study revealed that the new type-I counter
      current chromatography with a multilayer coil has a high application potential.

PMID- 29456157
TI  - [Yoga as an alternative to a sedentary lifestyle].

PMID- 29456159
TI  - CD150high Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and
      Immune Privilege via Adenosine.
AB  - A crucial player in immune regulation, FoxP3+ regulatory T cells (Tregs) are
      drawing attention for their heterogeneity and noncanonical functions. Here, we
      describe a Treg subpopulation that controls hematopoietic stem cell (HSC)
      quiescence and engraftment. These Tregs highly expressed an HSC marker, CD150,
      and localized within the HSC niche in the bone marrow (BM). Specific reduction of
      BM Tregs achieved by conditional deletion of CXCR4 in Tregs increased HSC numbers
      in the BM. Adenosine generated via the CD39 cell surface ectoenzyme on niche
      Tregs protected HSCs from oxidative stress and maintained HSC quiescence. In
      transplantation settings, niche Tregs prevented allogeneic (allo-) HSC rejection
      through adenosine and facilitated allo-HSC engraftment. Furthermore, transfer of
      niche Tregs promoted allo-HSC engraftment to a much greater extent than transfer
      of other Tregs. These results identify a unique niche-associated Treg subset and
      adenosine as regulators of HSC quiescence, abundance, and engraftment, further
      highlighting their therapeutic utility.

PMID- 29456158
TI  - Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo.
AB  - Cancer cells and embryonic tissues share a number of cellular and molecular
      properties, suggesting that induced pluripotent stem cells (iPSCs) may be
      harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing
      revealed that human and murine iPSCs express tumor-associated antigens, and we
      show here a proof of principle for using irradiated iPSCs in autologous anti
      tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in
      syngeneic murine breast cancer, mesothelioma, and melanoma models. As an
      adjuvant, the iPSC vaccine inhibited melanoma recurrence at the resection site
      and reduced metastatic tumor load, which was associated with fewer Th17 cells and
      increased CD11b+GR1hi myeloid cells. Adoptive transfer of T cells isolated from
      vaccine-treated tumor-bearing mice inhibited tumor growth in unvaccinated
      recipients, indicating that the iPSC vaccine promotes an antigen-specific anti
      tumor T cell response. Our data suggest an easy, generalizable strategy for
      multiple types of cancer that could prove highly valuable in clinical
      immunotherapy.

PMID- 29456160
TI  - Hypercholinergic activity in LRRK2 Parkinson's disease.

PMID- 29456162
TI  - The SeLECT score is useful to predict post-stroke epilepsy.

PMID- 29456161
TI  - The effect of LRRK2 mutations on the cholinergic system in manifest and
      premanifest stages of Parkinson's disease: a cross-sectional PET study.
AB  - BACKGROUND: Markers of neuroinflammation are increased in some patients with
      LRRK2 Parkinson's disease compared with individuals with idiopathic Parkinson's
      disease, suggesting possible differences in disease pathogenesis. Previous PET
      studies have suggested amplified dopamine turnover and preserved serotonergic
      innervation in LRRK2 mutation carriers. We postulated that patients with LRRK2
      mutations might show abnormalities of central cholinergic activity, even before
      the diagnosis of Parkinson's disease. METHODS: Between June, 2009, and December,
      2015, we recruited participants from four movement disorder clinics in Canada,
      Norway, and the USA. Patients with Parkinson's disease were diagnosed by movement
      disorder neurologists on the basis of the UK Parkinson's Disease Society Brain
      Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger
      sequencing. We used the PET tracer N-11C-methyl-piperidin-4-yl propionate to scan
      for acetylcholinesterase activity. The primary outcome measure was rate of
      acetylcholinesterase hydrolysis, calculated using the striatal input method. We
      compared acetylcholinesterase hydrolysis rates between groups using ANCOVA, with
      adjustment for age based on the results of linear regression analysis. FINDINGS:
      We recruited 14 patients with LRRK2 Parkinson's disease, 16 LRRK2 mutation
      carriers without Parkinson's disease, eight patients with idiopathic Parkinson's
      disease, and 11 healthy controls. We noted significant between-group differences
      in rates of acetylcholinesterase hydrolysis in cortical regions (average cortex
      p=0.009, default mode network-related regions p=0.006, limbic network-related
      regions p=0.020) and the thalamus (p=0.008). LRRK2 mutation carriers without
      Parkinson's disease had increased acetylcholinesterase hydrolysis rates compared
      with healthy controls in the cortex (average cortex, p=0.046). Patients with
      LRRK2 Parkinson's disease had significantly higher acetylcholinesterase activity
      in some cortical regions (average cortex p=0.043, default mode network-related
      regions p=0.021) and the thalamus (thalamus p=0.004) compared with individuals
      with idiopathic disease. Acetylcholinesterase hydrolysis rates in healthy
      controls were correlated inversely with age. INTERPRETATION: LRRK2 mutations are
      associated with significantly increased cholinergic activity in the brain in
      mutation carriers without Parkinson's disease compared with healthy controls and
      in LRRK2 mutation carriers with Parkinson's disease compared with individuals
      with idiopathic disease. Changes in cholinergic activity might represent early
      and sustained attempts to compensate for LRRK2-related dysfunction, or alteration
      of acetylcholinesterase in non-neuronal cells. FUNDING: Michael J Fox Foundation,
      National Institutes of Health, and Pacific Alzheimer Research Foundation.

PMID- 29456163
TI  - Association of Air Pollution Exposure and Interleukin-13 Haplotype with the Risk
      of Aggregate Bronchitic Symptoms in Children.
AB  - Interleukin-13(IL-13) might play an important role in driving aggregate
      bronchitic symptoms pathogenesis. However, none of the studies assessed the
      interaction between air pollutants exposure and IL-13 gene on the risk of
      aggregate bronchitic symptoms in non-asthma children. To assess the independent
      and joint effects of the exposure to air pollution and IL-13 haplotypes on the
      risk of aggregate bronchitic symptoms, we conducted a cross-sectional study and
      focused on non-asthma children. The study population consisted of 2944 children.
      The effect of each air pollutant on the risk of aggregate bronchitic symptoms was
      estimated as odds ratios per interquartile range (IQR) change. In the multiple
      logistic regressions, adjusted for confounding factors, the risk of chronic
      phlegm was associated with PM2.5 exposure (aOR, 1.59; 95% CI, 1.07-2.37 per
      12.51MUg/m3 change), O3 exposure (aOR, 1.54 95% CI, 1.05-2.27 per 8.28ppb change)
      and SO2 exposure (aOR, 1.19; 95% CI, 1.02-1.39 per 0.98ppb change). Our study
      further provides the evidence that gene-environment interactions between IL-13
      haplotype and O3 exposure on chronic phlegm (95% CI for interaction, 1.01-1.38).
      Identifying children who are more sensitive to air pollution helps us to provide
      them an efficient prevention to avoid aggregate bronchitic symptoms.

PMID- 29456165
TI  - Predicting melting and folding of nucleic acids: Comment on "DNA melting and
      energetics of double helix" by Alexander Vologodskii and Maxim D. Frank
      Kamenetskii.

PMID- 29456166
TI  - Head stabilisation in fast running lizards.
AB  - The cyclic patterns of terrestrial animal locomotion are frequently perturbed in
      natural environments. The terrain can be complex or inclined, the substrate can
      move unexpectedly and animals can misjudge situations. Loosing stability due to
      perturbations increases the probability of capture by predators and decreases the
      chance of successful prey capture and winning intraspecific battles. When
      controlled corrective actions are necessary to negotiate perturbations, animals
      rely on their exteroceptive and proprioceptive senses to monitor the environment
      and their own body movements. The vestibular system in the inner ear perceives
      linear and angular accelerations. This information enables gaze stabilisation and
      the creation of a stable, world-bound reference frame for the integration of the
      information of other senses. During locomotion, both functions are known to be
      facilitated by head stabilisation in several animals with an erect posture.
      Animals with a sprawled body posture, however, undergo very large body
      undulations while running. Using high speed video recordings, we tested whether
      they nevertheless stabilise their head during running, and how this is influenced
      by perturbations. We found that running Acanthodactylus boskianus lizards
      strongly stabilise their head yaw rotations when running on a flat, straight
      runway: the head rotation amplitude is only 4.76+/-0.99 degrees , while the
      adjacent trunk part rotates over 27.0+/-3.8 degrees . Lateral head translations
      are not stabilised (average amplitude of 7.4+/-2.0mm). When the lizards are
      experimentally perturbed by a large and unexpected lateral substrate movement,
      lateral translations of both the head and the body decrease (on average by 1.52+/
      0.81mm). At the same time, the rotations of the head and trunk also decrease (on
      average by 1.62 degrees +/-7.21 degrees ). These results show that head
      stabilisation intensifies because of the perturbation, which emphasises the
      importance of vestibular perception and balance in these fast and manoeuvrable
      animals.

PMID- 29456167
TI  - Comment on: "Emergency nurses' perspective of workplace violence in Jordanian
      hospitals: A national survey" Int. Emerg. Nurs. 24(1) (2016), 61-65 by ALBashtawy
      M and Aljezawi M.

PMID- 29456164
TI  - Pluripotent stem cells as a source of osteoblasts for bone tissue regeneration.
AB  - Appropriate and abundant sources of bone-forming osteoblasts are essential for
      bone tissue engineering. Pluripotent stem cells can self-renew and thereby offer
      a potentially unlimited supply of osteoblasts, a significant advantage over other
      cell sources. We generated mouse embryonic stem cells (ESCs) and induced
      pluripotent stem cells (iPSCs) from transgenic mice expressing rat 2.3 kb type I
      collagen promoter-driven green fluorescent protein (Col2.3GFP), a reporter of the
      osteoblast lineage. We demonstrated that Col2.3GFP ESCs and iPSCs can be
      successfully differentiated to osteoblast lineage cells that express Col2.3GFP in
      vitro. We harvested GFP+ osteoblasts differentiated from ESCs. Genome wide gene
      expression profiles validated that ESC- and iPSC-derived osteoblasts resemble
      calvarial osteoblasts, and that Col2.3GFP expression serves as a marker for
      mature osteoblasts. Our results confirm the cell identity of ESC- and iPSC
      derived osteoblasts and highlight the potential of pluripotent stem cells as a
      source of osteoblasts for regenerative medicine.

PMID- 29456168
TI  - Doppelganger research? Considerations on self-citations.

PMID- 29456169
TI  - Kinematics of lower limbs during walking are emulated by springy walking model
      with a compliantly connected, off-centered curvy foot.
AB  - The dynamics of the center of mass (CoM) during walking and running at various
      gait conditions are well described by the mechanics of a simple passive spring
      loaded inverted pendulum (SLIP). Due to its simplicity, however, the current form
      of the SLIP model is limited at providing any further information about multi
      segmental lower limbs that generate oscillatory CoM behaviors and their
      corresponding ground reaction forces. Considering that the dynamics of the CoM
      are simply achieved by mass-spring mechanics, we wondered whether any of the
      multi-joint motions could be demonstrated by simple mechanics. In this study, we
      expand a SLIP model of human locomotion with an off-centered curvy foot connected
      to the leg by a springy segment that emulates the asymmetric kinematics and
      kinetics of the ankle joint. The passive dynamics of the proposed expansion of
      the SLIP model demonstrated the empirical data of ground reaction forces, center
      of mass trajectories, ankle joint kinematics and corresponding ankle joint torque
      at various gait speeds. From the mechanically simulated trajectories of the ankle
      joint and CoM, the motion of lower-limb segments, such as thigh and shank angles,
      could be estimated from inverse kinematics. The estimation of lower limb
      kinematics showed a qualitative match with empirical data of walking at various
      speeds. The representability of passive compliant mechanics for the kinetics of
      the CoM and ankle joint and lower limb joint kinematics implies that the
      coordination of multi-joint lower limbs during gait can be understood with a
      mechanical framework.

PMID- 29456170
TI  - Corrigendum to "Flight style optimization in ski jumping on normal, large, and
      ski flying hills" [J. Biomech 47 (2014) 716-722].

PMID- 29456171
TI  - A magnetic resonance imaging framework for quantifying intervertebral disc
      deformation in vivo: Reliability and application to diurnal variations in lumbar
      disc shape.
AB  - Low back pain is a significant socioeconomic burden in the United States and
      lumbar intervertebral disc degeneration is frequently implicated as a cause. The
      discs play an important mechanical role in the spine, yet the relationship
      between disc function and back pain is poorly defined. The objective of this work
      was to develop a technique using magnetic resonance imaging (MRI) and three
      dimensional modeling to measure in vivo disc deformations. Using this method, we
      found that disc geometry was measurable with precision less than the in-plane
      dimensions of a voxel (~100 um, 10% of the MRI pixel size). Furthermore, there
      was excellent agreement between mean disc height, disc perimeter, disc volume and
      regional disc height measurements for multiple trials from an individual rater
      (standard deviation <3.1% across all measurements) and between mean height,
      perimeter, and volume measurements made by two independent raters (error <1.5%
      across all measurements). We then used this measurement system to track diurnal
      deformations in the L5-S1 disc in a young, healthy population (n = 8; age 24.1 +/
      3.3 yrs; 2 M/6F). We measured decreases in the mean disc height (-8%) and volume
      (-9%) with no changes in perimeter over an eight-hour workday. We found that the
      largest height losses occurred in the posterior (-13%) and posterior-lateral (
      14%) regions adjacent to the outer annulus fibrosus. Diurnal annulus fibrosus
      (AF) strains induced by posterior and posterior-lateral height loss may increase
      the risk for posterior disc herniation or posterior AF tears. These preliminary
      findings lay a foundation for determining how deviations from normal deformations
      may contribute to back pain.

PMID- 29456172
TI  - Effect of pediatric growth on cervical spine kinematics and deformations in
      automotive crashes.
AB  - Finite element (FE) models are a powerful tool that can be used to understand
      injury mechanisms and develop better safety systems. This study aims to extend
      the understanding of pediatric spine biomechanics, where there is a paucity of
      studies available. A newly developed and continuously scalable FE model was
      validated and scaled to 1.5-, 3-, 6-, 10-, 14- and 18-year-old using a non-linear
      scaling technique, accounting for local topological changes. The oldest and
      youngest ages were also scaled using homogeneous geometric scaling. To study the
      effect of pediatric spinal growth on head kinematics and intervertebral disc
      strain, the models were exerted to 3.5 g acceleration pulse at the T1 vertebra to
      simulate frontal, rear and side impacts. It was shown that the head rotation
      increases with age, but is over predicted when geometrically scaling down from 18
      to 1.5-year-old and under predicted when geometrically scaling up from 1.5- to
      18-year-old. The strain in the disc, however, showed a clear decrease with age in
      side impact and for the upper cervical spine in rear impact, indicating a higher
      susceptibility for neck injury at younger ages. In the frontal impact, no clear
      age dependence could be seen, suggesting a large contribution from changed facet
      joint angles, and lower levels of strain, suggesting a lower risk of injury. The
      results also highlight the benefit of rearward facing children in a seat limiting
      head lateral motion.

PMID- 29456173
TI  - [Failure mode and effects analysis to improve quality in clinical trials].
AB  - INTRODUCTION: The failure mode and effects analysis (FMEA) has been used as a
      tool in risk management and quality improvement. The objective of this study is
      to identify the weaknesses in processes in the clinical trials area, of a
      Pharmacy Department (PD) with great research activity, in order to improve the
      safety of the usual procedures. METHODS: A multidisciplinary team was created to
      analyse each of the critical points, identified as possible failure modes, in the
      development of clinical trial in the PD. For each failure mode, the possible
      cause and effect were identified, criticality was calculated using the risk
      priority number and the possible corrective actions were discussed. RESULTS: Six
      sub-processes were defined in the development of the clinical trials in PD. The
      FMEA identified 67 failure modes, being the dispensing and
      prescription/validation sub-processes the most likely to generate errors. All the
      improvement actions established in the AMFE were implemented in the Clinical
      Trials area. DISCUSSION: The FMEA is a useful tool in proactive risk management
      because it allows us to identify where we are making mistakes and analyze the
      causes that originate them, to prioritize and to adopt solutions to risk
      reduction. The FMEA improves process safety and quality in PD.

PMID- 29456174
TI  - Bilateral maculopathy after exposure to a laser pointer: Optical coherence
      tomography angiography findings.
AB  - CASE REPORT: A 36-year-old man went to the emergency department the day after
      exposure to a laser pointer. Funduscopy revealed dispersed macular pigment
      alterations, and optical coherence tomography showed a disruption of the retinal
      layers. The visual acuity was counting fingers in both eyes. Nine months later,
      optical coherence tomography angiography showed a rarefaction in the
      choriocapillaris vascular flow in the area of the laser injuries. DISCUSSION: The
      retinal layer mainly damaged by the laser injury was the retinal pigment
      epithelium. However, it is suggested that the laser injury could involve tissues
      beyond the retinal pigment epithelium, since a rarefaction of the
      choriocapillaris was found after exposure to the laser.

PMID- 29456175
TI  - Metformin-Induced Lactic Acidosis (MILA): Review of current diagnostic paradigm.
AB  - A new diagnostic paradigm has been proposed to better categorize causes of
      Metformin-Associated Lactic Acidosis (MALA). The diagnostic criteria defines a
      link between Metformin and lactic acidosis if lactate is >5mmol/L, Ph<7.35 and
      Metformin assay >5mg/L. Metformin assays are not readily available in emergency
      departments including nationwide Veteran's Affairs Hospitals; thereby making this
      proposed classification tool difficult to use in today's clinical practice. We
      describe a case report of a 45-year-old male, who took twice the amount of
      Metformin prescribed and presented with Metformin-induced lactic acidosis.
      According to the new criterion, our case would be classified as "Lactic Acidosis
      in Metformin-Treated Patients (LAMT)." However, the term LAMT does not
      distinguish between a septic patient taking Metformin with lactic acidosis, and a
      patient who ingested toxic amounts of Metformin and has lactic acidosis (in
      absence of Metformin assay). Our case highlights the importance of medication
      reconciliation done on arrival to emergency department. Timing and dosing of
      Metformin in patients who present to the emergency department with lactic
      acidosis may cinch the diagnosis of Metformin-Induced Lactic Acidosis (MILA) in
      the absence of a Metformin assay but in the right clinical context.

PMID- 29456176
TI  - Comment on: acid and nonacid gastroesophageal reflux after single anastomosis
      gastric bypass. An objective assessment using 24-hour multichannel intraluminal
      impedance-pH metry.

PMID- 29456177
TI  - Comment on: an update on bariatric tourism: time for a national registry?

PMID- 29456178
TI  - HOXB4 Promotes Hemogenic Endothelium Formation without Perturbing Endothelial
      Cell Development.
AB  - Generation of hematopoietic stem cells (HSCs) from pluripotent stem cells, in
      vitro, holds great promise for regenerative therapies. Primarily, this has been
      achieved in mouse cells by overexpression of the homeotic selector protein HOXB4.
      The exact cellular stage at which HOXB4 promotes hematopoietic development, in
      vitro, is not yet known. However, its identification is a prerequisite to
      unambiguously identify the molecular circuits controlling hematopoiesis, since
      the activity of HOX proteins is highly cell and context dependent. To identify
      that stage, we retrovirally expressed HOXB4 in differentiating mouse embryonic
      stem cells (ESCs). Through the use of Runx1(-/-) ESCs containing a doxycycline
      inducible Runx1 coding sequence, we uncovered that HOXB4 promoted the formation
      of hemogenic endothelium cells without altering endothelial cell development.
      Whole-transcriptome analysis revealed that its expression mediated the
      upregulation of transcription of core transcription factors necessary for
      hematopoiesis, culminating in the formation of blood progenitors upon initiation
      of Runx1 expression.

PMID- 29456179
TI  - The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program
      Essential for the Maintenance of Adult Hematopoietic Stem Cells.
AB  - Self-renewal and differentiation of adult stem cells are tightly regulated partly
      through configuration of chromatin structure by chromatin remodelers. Using
      knockout mice, we here demonstrate that bromodomain PHD finger transcription
      factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin
      remodeling complex, is essential for maintaining the population size of
      hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic
      stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted
      hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound
      defects including bone marrow failure and anemia. Genome-wide transcriptome
      profiling revealed that BPTF loss caused downregulation of HSC-specific gene
      expression programs, which contain several master transcription factors (Meis1,
      Pbx1, Mn1, and Lmo2) required for HSC maintenance and self-renewal. Furthermore,
      we show that BPTF potentiates the chromatin accessibility of key HSC "stemness"
      genes. These results demonstrate an essential requirement of the chromatin
      remodeler BPTF and NURF for activation of "stemness" gene-expression programs and
      proper function of adult HSCs.

PMID- 29456180
TI  - RAS Regulates the Transition from Naive to Primed Pluripotent Stem Cells.
AB  - The transition from naive to primed state of pluripotent stem cells is hallmarked
      by epithelial-mesenchymal transition, metabolic switch from oxidative
      phosphorylation to aerobic glycolysis, and changes in the epigenetic landscape.
      Since these changes are also seen as putative hallmarks of neoplastic cell
      transformation, we hypothesized that oncogenic pathways may be involved in this
      process. We report that the activity of RAS is repressed in the naive state of
      mouse embryonic stem cells (ESCs) and that all three RAS isoforms are
      significantly activated upon early differentiation induced by LIF withdrawal,
      embryoid body formation, or transition to the primed state. Forced expression of
      active RAS and RAS inhibition have shown that RAS regulates glycolysis, CADHERIN
      expression, and the expression of repressive epigenetic marks in pluripotent stem
      cells. Altogether, this study indicates that RAS is located at a key junction of
      early ESC differentiation controlling key processes in priming of naive cells.

PMID- 29456181
TI  - An Ultraconserved Element Containing lncRNA Preserves Transcriptional Dynamics
      and Maintains ESC Self-Renewal.
AB  - Ultraconserved elements (UCEs) show the peculiar feature to retain extended
      perfect sequence identity among human, mouse, and rat genomes. Most of them are
      transcribed and represent a new family of long non-coding RNAs (lncRNAs), the
      transcribed UCEs (T-UCEs). Despite their involvement in human cancer, the
      physiological role of T-UCEs is still unknown. Here, we identify a lncRNA
      containing the uc.170+, named T-UCstem1, and provide in vitro and in vivo
      evidence that it plays essential roles in embryonic stem cells (ESCs) by
      modulating cytoplasmic miRNA levels and preserving transcriptional dynamics.
      Specifically, while T-UCstem1::miR-9 cytoplasmic interplay regulates ESC
      proliferation by reducing miR-9 levels, nuclear T-UCstem1 maintains ESC self
      renewal and transcriptional identity by stabilizing polycomb repressive complex 2
      on bivalent domains. Altogether, our findings provide unprecedented evidence that
      T-UCEs regulate physiological cellular functions and point to an essential role
      of T-UCstem1 in preserving ESC identity.

PMID- 29456182
TI  - Mitochondrial Dysfunctions Contribute to Hypertrophic Cardiomyopathy in Patient
      iPSC-Derived Cardiomyocytes with MT-RNR2 Mutation.
AB  - Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac
      death in young individuals. A potential role of mtDNA mutations in HCM is known.
      However, the underlying molecular mechanisms linking mtDNA mutations to HCM
      remain poorly understood due to lack of cell and animal models. Here, we
      generated induced pluripotent stem cell-derived cardiomyocytes (HCM-iPSC-CMs)
      from human patients in a maternally inherited HCM family who carry the m.2336T>C
      mutation in the mitochondrial 16S rRNA gene (MT-RNR2). The results showed that
      the m.2336T>C mutation resulted in mitochondrial dysfunctions and ultrastructure
      defects by decreasing the stability of 16S rRNA, which led to reduced levels of
      mitochondrial proteins. The ATP/ADP ratio and mitochondrial membrane potential
      were also reduced, thereby elevating the intracellular Ca2+ concentration, which
      was associated with numerous HCM-specific electrophysiological abnormalities. Our
      findings therefore provide an innovative insight into the pathogenesis of
      maternally inherited HCM.

PMID- 29456183
TI  - Modeling Human Cardiac Hypertrophy in Stem Cell-Derived Cardiomyocytes.
AB  - Cardiac hypertrophy accompanies many forms of cardiovascular diseases. The
      mechanisms behind the development and regulation of cardiac hypertrophy in the
      human setting are poorly understood, which can be partially attributed to the
      lack of a human cardiomyocyte-based preclinical test system recapitulating
      features of diseased myocardium. The objective of our study is to determine
      whether human embryonic stem cell-derived cardiomyocytes (hESC-CMs) subjected to
      mechanical stretch can be used as an adequate in vitro model for studying
      molecular mechanisms of cardiac hypertrophy. We show that hESC-CMs subjected to
      cyclic stretch, which mimics mechanical overload, exhibit essential features of a
      hypertrophic state on structural, functional, and gene expression levels. The
      presented hESC-CM stretch approach provides insight into molecular mechanisms
      behind mechanotransduction and cardiac hypertrophy and lays groundwork for the
      development of pharmacological approaches as well as for discovering potential
      circulating biomarkers of cardiac dysfunction.

PMID- 29456184
TI  - Quantified F-Actin Morphology Is Predictive of Phagocytic Capacity of Stem Cell
      Derived Retinal Pigment Epithelium.
AB  - With stem cell-derived retinal pigment epithelial (RPE) replacement therapies in
      clinical testing, establishing potency of RPE prior to transplantation is
      imperative. Phagocytosis of photoreceptor outer segment fragments (POS) is a key
      indicator of RPE functionality. Comparing RPE derived from different donor human
      adult RPE stem cell lines, we found that cells were either high-phagocytic or low
      phagocytic despite sharing phagocytic receptors and ligands, junctional ZO-1, and
      lack of epithelial-mesenchymal transition. We found that low-phagocytic cells
      harbored F-actin stress fibers but lacked contiguous lateral circumferential F
      actin and ezrin-rich microvilli of high-phagocytic cells. Rho kinase inhibition
      reversed the F-actin phenotype and restored phagocytic capacity to low-phagocytic
      RPE. Conversely, RhoA activation induced stress fiber formation and reduced
      phagocytic function of high-phagocytic RPE. These results demonstrate that a
      stress fiber-rich microfilament cytoskeleton causes phagocytic dysfunction of RPE
      cells. We propose F-actin assessment as a rapid, sensitive, and quantitative test
      to identify RPE populations lacking phagocytic capacity.

PMID- 29456185
TI  - Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved
      Functionality Compared with Conventional Astrocytic Models.
AB  - In vivo studies of human brain cellular function face challenging ethical and
      practical difficulties. Animal models are typically used but display distinct
      cellular differences. One specific example is astrocytes, recently recognized for
      contribution to neurological diseases and a link to the genetic risk factor
      apolipoprotein E (APOE). Current astrocytic in vitro models are questioned for
      lack of biological characterization. Here, we report human induced pluripotent
      stem cell (hiPSC)-derived astroglia (NES-Astro) developed under defined
      conditions through long-term neuroepithelial-like stem (ltNES) cells. We
      characterized NES-Astro and astrocytic models from primary sources, astrocytoma
      (CCF-STTG1), and hiPSCs through transcriptomics, proteomics, glutamate uptake,
      inflammatory competence, calcium signaling response, and APOE secretion. Finally,
      we assess modulation of astrocyte biology using APOE-annotated compounds,
      confirming hits of the cholesterol biosynthesis pathway in adult and hiPSC
      derived astrocytes. Our data show large diversity among astrocytic models and
      emphasize a cellular context when studying astrocyte biology.

PMID- 29456187
TI  - A Request for Clarification Regarding the Advanced Radiotherapy Technologies
      Network (ART-NET).

PMID- 29456186
TI  - Neurons Generated by Mouse ESCs with Hippocampal or Cortical Identity Display
      Distinct Projection Patterns When Co-transplanted in the Adult Brain.
AB  - The capability of generating neural precursor cells with distinct types of
      regional identity in vitro has recently opened new opportunities for cell
      replacement in animal models of neurodegenerative diseases. By manipulating Wnt
      and BMP signaling, we steered the differentiation of mouse embryonic stem cells
      (ESCs) toward isocortical or hippocampal molecular identity. These two types of
      cells showed different degrees of axonal outgrowth and targeted different regions
      when co-transplanted in healthy or lesioned isocortex or in hippocampus. In
      hippocampus, only precursor cells with hippocampal molecular identity were able
      to extend projections, contacting CA3. Conversely, isocortical-like cells were
      capable of extending long-range axonal projections only when transplanted in
      motor cortex, sending fibers toward both intra- and extra-cortical targets.
      Ischemic damage induced by photothrombosis greatly enhanced the capability of
      isocortical-like cells to extend far-reaching projections. Our results indicate
      that neural precursors generated by ESCs carry intrinsic signals specifying
      axonal extension in different environments.

PMID- 29456188
TI  - Parasitism and the Biodiversity-Functioning Relationship.
AB  - Species interactions can influence ecosystem functioning by enhancing or
      suppressing the activities of species that drive ecosystem processes, or by
      causing changes in biodiversity. However, one important class of species
      interactions - parasitism - has been little considered in biodiversity and
      ecosystem functioning (BD-EF) research. Parasites might increase or decrease
      ecosystem processes by reducing host abundance. Parasites could also increase
      trait diversity by suppressing dominant species or by increasing within-host
      trait diversity. These different mechanisms by which parasites might affect
      ecosystem function pose challenges in predicting their net effects. Nonetheless,
      given the ubiquity of parasites, we propose that parasite-host interactions
      should be incorporated into the BD-EF framework.

PMID- 29456189
TI  - Programmable RNA Cleavage and Recognition by a Natural CRISPR-Cas9 System from
      Neisseria meningitidis.
AB  - The microbial CRISPR systems enable adaptive defense against mobile elements and
      also provide formidable tools for genome engineering. The Cas9 proteins are type
      II CRISPR-associated, RNA-guided DNA endonucleases that identify double-stranded
      DNA targets by sequence complementarity and protospacer adjacent motif (PAM)
      recognition. Here we report that the type II-C CRISPR-Cas9 from Neisseria
      meningitidis (Nme) is capable of programmable, RNA-guided, site-specific cleavage
      and recognition of single-stranded RNA targets and that this ribonuclease
      activity is independent of the PAM sequence. We define the mechanistic feature
      and specificity constraint for RNA cleavage by NmeCas9 and also show that
      nuclease null dNmeCas9 binds to RNA target complementary to CRISPR RNA. Finally,
      we demonstrate that NmeCas9-catalyzed RNA cleavage can be blocked by three
      families of type II-C anti-CRISPR proteins. These results fundamentally expand
      the targeting capacities of CRISPR-Cas9 and highlight the potential utility of
      NmeCas9 as a single platform to target both RNA and DNA.

PMID- 29456190
TI  - PINK1 Phosphorylates MIC60/Mitofilin to Control Structural Plasticity of
      Mitochondrial Crista Junctions.
AB  - Mitochondrial crista structure partitions vital cellular reactions and is
      precisely regulated by diverse cellular signals. Here, we show that, in
      Drosophila, mitochondrial cristae undergo dynamic remodeling among distinct
      subcellular regions and the Parkinson's disease (PD)-linked Ser/Thr kinase PINK1
      participates in their regulation. Mitochondria increase crista junctions and
      numbers in selective subcellular areas, and this remodeling requires PINK1 to
      phosphorylate the inner mitochondrial membrane protein MIC60/mitofilin, which
      stabilizes MIC60 oligomerization. Expression of MIC60 restores crista structure
      and ATP levels of PINK1-null flies and remarkably rescues their behavioral
      defects and dopaminergic neurodegeneration. In an extension to human relevance,
      we discover that the PINK1-MIC60 pathway is conserved in human neurons, and
      expression of several MIC60 coding variants in the mitochondrial targeting
      sequence found in PD patients in Drosophila impairs crista junction formation and
      causes locomotion deficits. These findings highlight the importance of
      maintenance and plasticity of crista junctions to cellular homeostasis in vivo.

PMID- 29456192
TI  - Low-dose versus standard-dose azithromycin for treatment of yaws.

PMID- 29456194
TI  - The Global Fund and Heineken.

PMID- 29456193
TI  - Changes in shoulder girdle strength in 3 consecutive years in elite adolescent
      swimmers: a longitudinal cohort study.
AB  - BACKGROUND: The shoulder complex is highly loaded during swimming. No studies
      were found analyzing the changes in shoulder girdle strength in young swimmers,
      through the years. OBJECTIVE: To analyze the changes in strength of internal
      rotators and external rotators of the arm, lower trapezius and supraspinatus and
      in the external rotators/internal rotators ratio in young elite swimmers through
      3 years. METHODS: 31 adolescent elite swimmers (14-18 years, of both sexes)
      participated in the study. Isometric strength of the shoulder girdle muscles was
      performed using a handheld dynamometer during 3 years. RESULTS: For boys absolute
      data, internal rotators increased from the first to the second (p=0.0001; mean
      difference 45.6N; 95%CI 26.7-65.0) and third years (p=0.01; mean difference:
      32.4; 95%CI: 9.3-55.5). Considering the weight-normalized data, internal rotators
      increased from the first to the second year (p<0.0001; mean difference: 0.52;
      95%CI: 0.26-0.78), external rotators decreased from the first to the third year
      (p=0.003; mean difference: -0.33; 95%CI: -0.53 to -0.13) and from the second to
      the third year (p=0.0004; mean difference: -0.29; 95%CI: -0.46 to -0.12) and
      supraspinatus decreased from the second to the third year (p=0.006; mean
      difference: -0.17; 95%CI: -0.28 to -0.06). For girls, there were no significant
      differences in the absolute strength. Considering the weight-normalized data,
      lower trapezius decreased from the first to the third year (p=0.02; mean
      difference: -0.15; 95%CI: -0.27 to 0.03). Considering both sexes, the external
      rotators/internal rotators ratio decreased from the first to the second
      (p<0.0001; mean difference -0.12N; 95%CI -0.13 to -0.11) and third years
      (p<0.0001; mean difference -0.15N; 95%CI -0.16 to -0.14). CONCLUSION: Muscle
      imbalance can occur in the shoulder girdle in young swimmers in 3 years, with
      increased internal rotators and decreased external rotators and supraspinatus
      strength in boys, and decreased strength of the lower trapezius in girls.
      Attention should be given in young swimmers' shoulder girdle muscle balance.

PMID- 29456191
TI  - Comparative efficacy of low-dose versus standard-dose azithromycin for patients
      with yaws: a randomised non-inferiority trial in Ghana and Papua New Guinea.
AB  - BACKGROUND: A dose of 30 mg/kg of azithromycin is recommended for treatment of
      yaws, a disease targeted for global eradication. Treatment with 20 mg/kg of
      azithromycin is recommended for the elimination of trachoma as a public health
      problem. In some settings, these diseases are co-endemic. We aimed to determine
      the efficacy of 20 mg/kg of azithromycin compared with 30 mg/kg azithromycin for
      the treatment of active and latent yaws. METHODS: We did a non-inferiority, open
      label, randomised controlled trial in children aged 6-15 years who were recruited
      from schools in Ghana and schools and the community in Papua New Guinea.
      Participants were enrolled based on the presence of a clinical lesion that was
      consistent with infectious primary or secondary yaws and a positive rapid
      diagnostic test for treponemal and non-treponemal antibodies. Participants were
      randomly assigned (1:1) to receive either standard-dose (30 mg/kg) or low-dose
      (20 mg/kg) azithromycin by a computer-generated random number sequence. Health
      care workers assessing clinical outcomes in the field were not blinded to the
      patient's treatment, but investigators involved in statistical or laboratory
      analyses and the participants were blinded to treatment group. We followed up
      participants at 4 weeks and 6 months. The primary outcome was cure at 6 months,
      defined as lesion healing at 4 weeks in patients with active yaws and at least a
      four-fold decrease in rapid plasma reagin titre from baseline to 6 months in
      patients with active and latent yaws. Active yaws was defined as a skin lesion
      that was positive for Treponema pallidum ssp pertenue in PCR testing. We used a
      non-inferiority margin of 10%. This trial was registered with ClinicalTrials.gov,
      number NCT02344628. FINDINGS: Between June 12, 2015, and July 2, 2016, 583
      (65.1%) of 895 children screened were enrolled; 292 patients were assigned a low
      dose of azithromycin and 291 patients were assigned a standard dose of
      azithromycin. 191 participants had active yaws and 392 had presumed latent yaws.
      Complete follow-up to 6 months was available for 157 (82.2%) of 191 patients with
      active yaws. In cases of active yaws, cure was achieved in 61 (80.3%) of 76
      patients in the low-dose group and in 68 (84.0%) of 81 patients in the standard
      dose group (difference 3.7%; 95% CI -8.4 to 15.7%; this result did not meet the
      non-inferiority criterion). There were no serious adverse events reported in
      response to treatment in either group. The most commonly reported adverse event
      at 4 weeks was gastrointestinal upset, with eight (2.7%) participants in each
      group reporting this symptom. INTERPRETATION: In this study, low-dose
      azithromycin did not meet the prespecified non-inferiority margin compared with
      standard-dose azithromycin in achieving clinical and serological cure in PCR
      confirmed active yaws. Only a single participant (with presumed latent yaws) had
      definitive serological failure. This work suggests that 20 mg/kg of azithromycin
      is probably effective against yaws, but further data are needed. FUNDING:
      Coalition for Operational Research on Neglected Tropical Diseases.

PMID- 29456195
TI  - Mast cell tryptase changes with Aspergillus fumigatus - Host crosstalk in cystic
      fibrosis patients.
AB  - Pulmonary and systemic antifungal immunity influences quality of life and
      survival of people with cystic fibrosis. Aspergillus fumigatus (Af) induces
      specific IgG and IgE. Mast cells respond to IgE, IgG and direct interactions with
      Af. Mast cells are the source of the protease tryptase. We aimed at evaluating
      serum baseline tryptase as a potential biomarker of the Af-host interaction in
      cystic fibrosis patients. Serum baseline tryptase, IgE and IgG directed to Af
      extract and Af molecular allergens were measured in 76 cystic fibrosis patients.
      The main findings were (i) lower levels of serum baseline tryptase in patients
      displaying specific IgE to Af (p < 0.0001) and (ii) an association between
      tryptase levels and IgE or IgG responses to Af and ribotoxin (Asp f 1). These
      findings suggest that serum baseline tryptase is influenced by Af-host
      interactions and thus might be a marker for mast cell regulation and pulmonary
      immune defenses.

PMID- 29456196
TI  - Improvement in Exophiala dermatitidis airway persistence and respiratory decline
      in response to interferon-gamma therapy in a patient with cystic fibrosis.

PMID- 29456197
TI  - Clinical usefulness and accuracy of polymerase chain reaction in the detection of
      bacterial meningitis agents in pediatric cerebrospinal fluid.
AB  - Bacterial meningitis poses enormous healthcare challenges due to a high
      mortality, morbidity and sequelae. Neisseria (N.) meningitidis, Haemophilus (H.)
      influenzae, Streptococcus (S.) pneumoniae and S. agalactiae remain among the most
      prevalent infectious agents that cause bacterial meningitis in children. The
      objective of this study was the simultaneous detection of these pathogens in
      suspected cerebrospinal fluid (CSF) by using multiplex polymerase chain reaction
      (mPCR) and compare PCR results with standard diagnostics currently used in
      clinical practice. CSF specimens were obtained from 515 children (<5 years)
      clinically suspected of having acute bacterial meningitis. Based on bacterial
      culture, four isolates of salmonella sp and one Citrobacter freundii isolate were
      identified. The remaining 510 CSF specimens, having negative culture, were
      subjected to mPCR. Twenty-three (4.51%) CSF samples yielded a PCR positive
      signal. The pathogens identified were: S. pneumoniae (n=13), H. influenzae (n=7)
      and N. meningitidis (n=3). S. agalactiae was not detected. Using sequential
      multiplex PCR, serogrouping of S. pneumoniae revealed 3 different serotypes:
      serotype 19A (n=6), 19F (n=4) and serotype 23F (n=3). Only the serotype A was
      identified for the 3N. meningitidis isolates. Despite vaccination, S. pneumoniae
      remains a leading cause of pediatric invasive disease. Detecting causative
      organism remains the most critical aspect for management of children with
      suspected meningitis. PCR method is more sensitive and rapid than culture for
      detecting the infectious agents. Institution of PCR diagnostics is recommended
      for early and appropriate therapy.

PMID- 29456198
TI  - A modified single-loop reconstruction after pancreaticoduodenectomy reduces
      severity of postoperative pancreatic fistula in high-risk patients.
AB  - BACKGROUND: Double-loop (DL) reconstruction after pancreaticoduodenectomy (PD),
      diverting pancreatic from biliary secretions, has been reported to reduce rates
      and severity of postoperative pancreatic fistula (POPF) compared to single loop
      (SL) reconstruction at the price of prolonged operative duration. This study
      investigated the feasibility of a new reconstruction method combining the
      advantages of DL with the simplicity of SL in patients with high-risk pancreas.
      METHODS: A modified single-loop (mSL) reconstruction was used in patients
      undergoing PD with a soft pancreatic remnant and a pancreatic duct smaller than 3
      mm (n = 50). The loop between the pancreatic and the biliary anastomoses was left
      longer and a side-to-side jejunojejunal anastomosis was performed between them at
      the lowest point to promote isolated flow of pancreatic and biliary secretions.
      Rate and severity of POPF, mortality, duration of surgery, and POPF-associated
      morbidity were compared to those of 50 matched patients with SL and 25 patients
      with DL reconstruction. RESULTS: Duration of surgery was 57 min longer for DL,
      but equal for mSL and SL. The POPF rate did not differ between the three groups.
      The severity of POPF was more pronounced in the SL group (62% grade C: p =
      0.011). Mortality and major morbidity were lower and hospital stay shorter in the
      mSL and DL groups compared to the SL group. CONCLUSIONS: The new mSL
      reconstruction was safer than conventional SL and faster to perform than DL
      reconstruction in patients with a high-risk pancreas. It did not influence the
      rate of POPF, but reduced its severity, leading to less major morbidity and
      mortality.

PMID- 29456199
TI  - The liver-first approach for synchronous colorectal liver metastases: more than a
      decade of experience in a single centre.
AB  - BACKGROUND: The feasibility of the liver-first approach for synchronous
      colorectal liver metastases (CRLM) has been established. We sought to assess the
      short-term and long-term outcomes for these patients. METHODS: Outcomes of
      patients who underwent a liver-first approach for CRLM between 2005 and 2015 were
      retrospectively evaluated from a prospective database. RESULTS: Of the 92
      patients planned to undergo the liver-first strategy, the paradigm could be
      completed in 76.1%. Patients with concurrent extrahepatic disease failed
      significantly more often in completing the protocol (67% versus 21%; p = 0.03).
      Postoperative morbidity and mortality were 31.5% and 3.3% following liver
      resection and 30.9% and 0% after colorectal surgery. Of the 70 patients in whom
      the paradigm was completed, 36 patients (51.4%) developed recurrent disease after
      a median interval of 20.9 months. The median overall survival on an intention-to
      treat basis was 33.1 months (3- and 5-year overall survival: 48.5% and 33.1%).
      Patients who were not able to complete their therapeutic paradigm had a
      significantly worse overall outcome (p = 0.03). CONCLUSION: The liver-first
      approach is feasible with acceptable perioperative morbidity and mortality rates.
      Despite the considerable overall-survival-benefit, recurrence rates remain high.
      Future research should focus on providing selection tools to enable the optimal
      treatment sequence for each patient with synchronous CRLM.

PMID- 29456200
TI  - Diagnostic validity of methods for assessment of swallowing sounds: a systematic
      review.
AB  - INTRODUCTION: Oropharyngeal dysphagia is a highly prevalent comorbidity in
      neurological patients and presents a serious health threat, which may lead to
      outcomes of aspiration pneumonia, ranging from hospitalization to death. This
      assessment proposes a non-invasive, acoustic-based method to differentiate
      between individuals with and without signals of penetration and aspiration.
      OBJECTIVE: This systematic review evaluated the diagnostic validity of different
      methods for assessment of swallowing sounds, when compared to videofluroscopy
      swallowing study to detect oropharyngeal dysphagia. METHODS: Articles in which
      the primary objective was to evaluate the accuracy of swallowing sounds were
      searched in five electronic databases with no language or time limitations.
      Accuracy measurements described in the studies were transformed to construct
      receiver operating characteristic curves and forest plots with the aid of Review
      Manager v. 5.2 (The Nordic Cochrane Centre, Copenhagen, Denmark). The methodology
      of the selected studies was evaluated using the Quality Assessment Tool for
      Diagnostic Accuracy Studies-2. RESULTS: The final electronic search revealed 554
      records, however only 3 studies met the inclusion criteria. The accuracy values
      (area under the curve) were 0.94 for microphone, 0.80 for doppler, and 0.60 for
      stethoscope. CONCLUSION: Based on limited evidence and low methodological quality
      because few studies were included, with a small sample size, from all index
      testes found for this systematic review, doppler showed excellent diagnostic
      accuracy for the discrimination of swallowing sounds, whereas microphone-reported
      good accuracy discrimination of swallowing sounds of dysphagic patients and
      stethoscope showed best screening test.

PMID- 29456201
TI  - Modular radical cross-coupling with sulfones enables access to sp3-rich
      (fluoro)alkylated scaffolds.
AB  - Cross-coupling chemistry is widely applied to carbon-carbon bond formation in the
      synthesis of medicines, agrochemicals, and other functional materials. Recently,
      single-electron-induced variants of this reaction class have proven particularly
      useful in the formation of C(sp2)-C(sp3) linkages, although certain compound
      classes have remained a challenge. Here, we report the use of sulfones to
      activate the alkyl coupling partner in nickel-catalyzed radical cross-coupling
      with aryl zinc reagents. This method's tolerance of fluoroalkyl substituents
      proved particularly advantageous for the streamlined preparation of
      pharmaceutically oriented fluorinated scaffolds that previously required multiple
      steps, toxic reagents, and nonmodular retrosynthetic blueprints. Five specific
      sulfone reagents facilitate the rapid assembly of a vast set of compounds, many
      of which contain challenging fluorination patterns.

PMID- 29456202
TI  - Contrast-induced nephropathy: Pathophysiology, risk factors, and prevention.
AB  - Contrast-induced acute kidney injury is a common iatrogenic complication
      associated with increased health resource utilization and adverse outcomes,
      including short- and long-term mortality and accelerated progression of
      preexisting renal insufficiency. The incidence of contrast-induced nephropathy
      (CIN) has been reported to range from 0% to 24%. This wide range reported by the
      studies is due to differences in definition, background risk factors, type and
      dose of contrast medium used, and the frequency of other coexisting potential
      causes of acute renal failure. CIN is usually transient, with serum creatinine
      levels peaking at 2-3 days after administration of contrast medium and returning
      to baseline within 7-10 days after administration. Multiple studies have been
      conducted using variety of therapeutic interventions in an attempt to prevent
      CIN. Of these, careful selection of patients, using newer radiocontrast agents,
      maintenance of hydration status, and avoiding nephrotoxic agents pre- and post
      procedure are the most effective interventions to protect against CIN. This
      review focuses on the basic concepts of CIN and summarizes our recent
      understanding of its pathophysiology. In addition, this article provides
      practical recommendations with respect to CIN prevention and management.

PMID- 29456203
TI  - Effect of vitamin E on reversibility of renal function following discontinuation
      of colistin in rats: Histological and biochemical investigations.
AB  - This study was carried out to evaluate spontaneous renal regeneration after
      stopping colistin methanesulfonate (CMS), which induces tubular damage, and the
      curative effect of Vitamin E (vit E) in rats. Animals were given the following:
      sterile saline (n = 6), 300,000 IU/kg/ day of CMS (n = 24), or 450,000 IU/kg/day
      of CMS (n = 24) for seven days. Each CMS group was subdivided into four subgroups
      (n = 6) and sacrificed as follows: (i) 12 h after stopping CMS, (ii) two weeks
      after stopping CMS, (iii) two weeks after stopping treatment with vit E, and (iv)
      two weeks after stopping treatment with olive oil. Subsequently, plasma
      creatinine (pCr), urine N-acetyl-b-D-glucosaminidase (NAG), renal tissue level of
      malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GSH),
      and renal histology were tested. CMS-induced tubular damage increased the NAG and
      MDA levels and decreased the SOD and GSH activities. After two weeks of stopping
      CMS, there was no significant renal recovery. However, treatment with vit E
      improved tubular regeneration and reduced the biochemical impairments. Two weeks
      might not be long enough for significant spontaneous renal regeneration.
      Improvement of renal parameters by vit E could be explained by the reduction of
      oxidative stress damage.

PMID- 29456204
TI  - Renoprotective effect of Nigella sativa against cisplatin-induced nephrotoxicity
      and oxidative stress in rat.
AB  - Cisplatin is one of the important antineoplastic drugs. Its clinical use has been
      restricted due to severe kidney toxicity. Nigella sativa (N. sativa) is an
      herbaceous plant with many pharmacologic effects. In the present study, we
      evaluated the protective effects of aqueous-ethanolic extract of N. sativa and
      Vitamin E on cisplatin-induced nephrotoxicity in rats. Eighty male rats were
      divided into eight groups: control, cisplatin (6 mg/kg; ip), preventive Vitamin E
      (100 mg/kg), preventive N. sativa (100,200 mg/kg), preventive + treatment Vitamin
      E, and preventive + treatment N. sativa (100, 200 mg/kg). Duration of this study
      was 11 days and cisplatin was injected on the 6th day of the experiment. Tissue
      damage in all groups that received N. sativa extract and Vitamin E showed a
      significant improvement compared with the cisplatin group. In addition, serum and
      tissue total thiol content in preventive and preventive + treatment N. sativa
      groups showed significant increase compared with cisplatin group. There was no
      significant difference in serum malondialdehyde concentration of the control rats
      compared with the preventive and preventive + treatment N. sativa groups. N.
      sativa extract and viamin E improved the pathology and oxidative stress in the
      rat kidney. However, more studies are needed to determine the mechanism of action
      of N. sativa on cisplatin-induced kidney toxicity.

PMID- 29456205
TI  - Mutational analysis of AGXT gene in Libyan children with primary hyperoxaluria
      type 1 at Tripoli Children Hospital.
AB  - Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism.
      It results from genetic mutation of the AGXT gene. The study objective was to
      verify the clinical and epidemiological patterns of PH1 in Libyan children at
      Tripoli Children Hospital confirmed by AGXT gene mutation. A descriptive case
      series study of 53 children with PH1 diagnosed between 1994 and 2015 was carried
      out in the Nephrology Unit at Tripoli Children Hospital. Diagnosis of PH1 was
      based on the clinical presentation (renal stones or nephrocalcinosis), positive
      family history of PH1, and high 24 h urinary oxalate. Sampling for AGXT gene
      mutation was collected from April 2012 to December. 2015. Among the 53 children
      included, males composed of 62.3% of patients. Their age at presentation ranged
      between two months and 20 years with a mean age of 55.4 +/- 48 months. The
      parents of 81.1% of these patients had positive consanguinity. Forty (75.5%)
      patients were from South West (mountain area), and 16 (40%) of them were from
      Yefrin. The most common mutation found in this study was c.731T>C (p.lle244thr)
      seen in 32 (71%) of children, and interestingly, among these patients, 87.1% were
      homozygous in gene typing, 86.2% had positive history of consanguinity, 71.4%
      were from South West (mountain area), 96.6% had family history of PH1, and 20%
      presented with impaired renal function. The patients with this mutation were
      younger at presentation than that with other genes, and it was more prevalent
      among boys (61.3%). Thus, the most common gene mutation found in Libyan children
      with PH1 was c.731T>C (p.lle244thr) and this is more likely due to the strong
      genetic pooling caused by the high consanguinity rate which requires an extensive
      genetic counseling.

PMID- 29456206
TI  - C4d-negative antibody-mediated rejection: A pathologist's perspective and
      clinical outcome.
AB  - Banff'13 update included C4d-antibody-mediated rejection (ABMR) as a separate
      entity responsible for graft dysfunction with limited clinical/prognostic
      implications. We present a retrospective study to determine the incidence and
      outcome of C4d-negative ABMR. A total of 987 renal allograft (RA) biopsies
      obtained from 987 RA recipients were studied from January 2013 to January 2016.
      All samples were subjected to light microscopy using standard stains and C4d
      immunohistochemistry on paraffin sections and reported according to modified
      Banff's criteria. Adequate biopsies with immunological injuries were categorized
      as Group 1: pure ABMR, Group 2: combined ABMR with concurrent T-cell-mediated
      rejection (TCR), and Group 3: pure TCR. Groups 1 and 2 were further subgrouped as
      C4d positive (Group 1a and 2a) or C4d negative (Group 1b and 2b). Graft function
      was measured by serum creatinine (SCr) level (mg/dL). Of the 987 biopsies, 43.3%
      (404) biopsies revealed immunological injury. Of these, 27.7% of the biopsies
      revealed pure ABMR (Group 1), 60.6% revealed combined ABMR with TCR (Group 2),
      and 11.3% revealed pure TCR (Group 3). The overall incidence of ABMR (pure ABMR +
      ABMR with TCR) was 36.27%, of which C4d-negative rejections were 18.48% and 18.7%
      in Group 1 and Group 2, respectively. The mean SCr at the end of three years
      follow-up in patients with C4d-negative rejections was comparatively higher. C4d
      negative ABMR, recently included in Banff'13, has a low incidence, usually
      presents early after transplantation but carries better outcome than C4d-positive
      ABMR. However, further long-term studies are still required for knowing the
      clinical course over years.

PMID- 29456207
TI  - Medical renal disease in tumor nephrectomies: The silent killer.
AB  - In tumor nephrectomy specimens, the evaluation of the normal renal parenchyma is
      often overlooked. A patient with both end-stage renal diseases (ESRDs) with a
      renal cell carcinoma is more likely to die of the ESRD rather than cancer. At the
      time of nephrectomy, a pathologist has a large amount of tissue available to him
      to comment upon the presence of disease in the nonneoplastic kidney. Hence, this
      study was undertaken with the idea of characterizing disease in the nonneoplastic
      kidney at the time of tumor nephrectomy. A two-year retrospective study was
      carried out on all tumor nephrectomies and partial nephrectomies. Glomerular,
      tubulointerstitial, and vascular compartments were evaluated for abnormalities.
      Twenty-four cases were included in the study. A total of 17 cases showed
      abnormalities in the nonneoplastic renal parenchyma. In the glomeruli, two cases
      showed IgA nephropathy, one case showed segmental sclerosis, and one case showed
      the presence of cellular crescents. A single case showed diabetic
      glomerulosclerosis. Interstitial fibrosis and tubular atrophy were noted in seven
      cases. Fifteen cases showed intimal sclerosis and medial hypertrophy and six
      cases showed nodular hyalinosis. Tumor nephrectomy specimens may very often show
      the presence of various nonneoplastic diseases. Hypertensive and diabetic renal
      disease are the major contributors, although primary glomerular diseases may also
      be present. At the time of the evaluation of a renal tumor on nephrectomy
      specimen, the status of the nonneoplastic kidney may become as an important
      predictor of clinical outcome as the tumor itself.

PMID- 29456208
TI  - Morbidity and mortality of hospitalized hip fractures in chronic hemodialysis.
AB  - Abnormal bone architecture contributes to high incidence of hip fractures in
      chronichemodialysis (HD) patients. Their clinical epidemiology is incompletely
      described. We conducted a retrospective cohort study to assess the implications
      ofhospitalization with hip fracture in HD patients compared to the nonchronic
      kidney disease population. Thirty-three chronic HD patients admitted with hip
      fracture overfiveyears were age- and sex-matched on a 1:1 ratio with controls
      that had hip fracture and normal renal function. Demographic characteristics,
      deaths, and readmissions atsixmonths,hospitalization length, time to operation,
      and laboratory resultswere recorded from electronic health files. Datawere
      compared betweenthe two groups usingpairedt-test for continuous variables and
      McNemar's test for categoricalvariables. The compositeendpoint of deathand/or
      readmission at6 months was higher in HD patients (12.1% vs. 6.2%, P<0.001).
      Furthermore, mean time tooperationwas more delayed due to comorbidities (4.7 vs.
      2.9 days, p = 0.04). HD patients had anemia more frequently at presentation
      (hemoglobin below 10 mg/dL, 32.1% vs. 12.5%, P = 0.003). Finally, they were more
      likely to be considered toofrail for surgery and not be operated (21.2% vs. 6.2%,
      P<0.001). Hip fractures are associated with increased morbidity and mortality and
      represent an important health-care burden for chronic HD patients. Future
      research is needed to identify definite predictors of adverse outcomes and to
      implement prevention strategies.

PMID- 29456209
TI  - Assessment of prevalence and clinical outcome of frailty in an elderly
      predialysis cohort using simple tools.
AB  - The relationship between frailty and chronic kidney disease in elderly population
      has been recognized; however, studies concentrating on frailty in predialysis
      patients are limited. For nephrologists, the recognition of frailty is important
      as it has impact on decisions on the choice of dialysis modality and sometimes on
      whether dialysis is indeed in the patients' best interests. Many of the tools for
      routine assessment of frailty are not easily applicable to those clinicians not
      practicing elderly care medicine. A tool needs to be simple and applicable for
      daily routine practice. The aim of this study was to assess the prevalence and
      clinical outcome of frailty in an elderly predialysis population using simple
      tools. A nonrandomized prospective study was conducted in which, 104 patients
      aged 65 years or above with an estimated glomerular filtration rate of 25 mL or
      less were included. Data including age, sex, renal function, calcium, albumin,
      parathormone, and comorbidities were collected at baseline and at three months
      interval for one year. Functional performance was assessed using Karnofsky scale.
      The Charlson comorbidity index was used to assess comorbid status of each
      patient. Frailty was assessed using a combination of PRISMA questionnaire and
      Timed up and Go test. End points were death or start of dialysis at 20-month
      follow-up. A frail group (n = 58; males = 32, females = 26) and a nonfrail group
      (n = 46; males = 21, females = 25) were identified. Frailty was prevalent in
      53.8% of the selected population. There was no significant difference between
      both groups in terms of age, gender, comorbidities, hemoglobin, inflammatory
      markers, or calcium hemostasis. Nine patients chose conservative management in
      the frail group and six in nonfrail group. Rate of death was significantly higher
      in the frail group (death = 14) compared to nonfrail group (death = 3; P = 0.01).
      There was no significant difference between both groups in terms of initiation of
      dialysis (P = 0.1). Frailty and Charlson comorbidity index were significantly
      associated with mortality (P = 0.023 and 0.032, respectively). Survival in frail
      patients who started peritoneal dialysis (PD) was slightly better than those
      started on hemodialysis (HD) with hazard ratio = 3.23 (P = 0.23). Our study shows
      that the prevalence of frailty and mortality rate is high among elderly
      predialysis patients. Frailty and Charlson comorbidity index are independent
      predictors of outcome in this population. PD might be a better option of dialysis
      modality compared to HD in the frail population.

PMID- 29456210
TI  - Appraising the outcome and complications of peritoneal dialysis patients in self
      care peritoneal dialysis and assisted peritoneal dialysis: A 5-year review of a
      single Saudi center.
AB  - Our objective is to study the outcomes and complications of peritoneal dialysis
      (PD) including comparison of self-care PD with home-care assisted PD during a
      five-year period. A retrospective study of PD data at King Saud University
      affiliated hospital in Riyadh from January 1, 2009, to December 31, 2013. One
      hundred and eleven patients were included (female 55%). The average age was 47.4
      (1-83) years. Twenty-one (18.91%) patients were on continuous ambulatory PD and
      90 (81.08%) on automated PD. The mean time on PD was 23.5 (3-60) months. At the
      end of five years, 47 (42.34%) patients were continuing on PD, 12 (10.81%) had
      renal transplant, 33 (29.73%) patients were transferred to hemodialysis, and two
      (1.8%) patients were transferred to other centers. Seventeen patients died during
      this period giving a mortality rate of 7.13 deaths/100 patient-year during the
      five-year period. Six patients died due to cardiovascular causes, while five had
      sepsis. There was one death each due to prostate cancer, hyperoxaluria, and toxic
      epidermal necrolysis. Three patients died suddenly at home. Peritonitis rate was
      one episode/35.28 patient/month or one episode/2.94 patient/year. We compared the
      results for patients doing the dialysis themselves [56 (50.45%)] "self-care PD"
      to 55 (49.5%) patients assisted by a family member or other caregivers "assisted
      PD." We found no significant difference in the incidence of complications,
      technical outcome, mortality, and peritonitis episodes. However, we found a high
      prevalence of diabetes mellitus and significant increase in exit site infection
      in assisted PD. Our study suggests that PD patients in Saudi Arabia have a good
      overall outcome. Furthermore, assisted PD showed good patient and technique
      outcome.

PMID- 29456211
TI  - Risk factors associated with acute kidney injury in newborns.
AB  - Acute kidney injury (AKI) in the newborn is a common problem in the neonatal
      intensive care unit with many underlying factors such as asphyxia, respiratory
      distress syndrome (RDS), and urogenital anomalies. The aim of this study is to
      highlight possible risk factors and profile of neonates developing AKI in the
      Neonatal Intensive Care Unit (NICU) of Cairo University Pediatric Hospital. The
      study was carried out on 90 neonates (30 patients and 60 controls), among
      neonates admitted to NICU. The study was done over two months, from January 2015
      to March 2015. Our study showed that sepsis was detected in 53.3%, prematurity in
      46.67%, RDS in 43.3%, congenital heart disease in 20%, and hypoxic-ischemic
      encephalopathy in 6.67% of patients. Maternal illness and low body temperature
      were both significant risk factors of AKI in neonates. History of maternal
      illness, low body temperature, sepsis, prematurity, and respiratory distress can
      contribute to the development of AKI in neonates.

PMID- 29456213
TI  - Association of serum fibroblast growth factor-23 with Doppler pulse wave velocity
      in hemodialysis patients.
AB  - We aimed to study the association of fibroblast growth factor-23 (FGF-23) as a
      novel cardiovascular risk factor with Doppler pulse wave velocity (PWV) as an
      arterial stiffness measuring tool in hemodialysis (HD) patients. We conducted a
      cross-sectional study in which blood samples from 86 HD patients were obtained to
      estimate FGF 23 and other parameters. Flow waveforms were obtained at two
      locations within right common carotid artery, and right femoral artery by Doppler
      ultrasound with ECG recorded in addition. The time differences between the R wave
      of the ECG signal and the onset of the flow waveforms at the two sites yield
      DeltaT. Distances between sampling sites were measured using a tape measure. PWV
      was defined as (m/s) = D (m)/ DeltaT (s). In the current study, we found
      significant positive correlations between Doppler PWV and both age (r = 0.401, P
      = 0.039) and systolic blood pressure (r = 0.602, P = 0.034), while no significant
      association between Doppler PWV and FGF-23 (r = 0.123, P = 0.259) could be
      detected. Serum FGF-23 levels are not significantly associated with Doppler PWV
      in HD patients.

PMID- 29456212
TI  - The epidemiology of acute peritonitis in end-stage renal disease patients on
      peritoneal dialysis in Qatar: An 8-year follow-up study.
AB  - Acute peritonitis (AP) is a common and devastating complication in end-stage
      renal disease patients on peritoneal dialysis (PD). We are reporting an
      epidemiologic study of AP in Qatar over 8-year follow-up. We retrospectively
      reviewed medical records of all PD patients in Qatar from 2007 to 2014. The
      analysis was conducted to report epidemiology, outcome, and associated risk
      factors of AP. We had 318 AP episodes in 180 patients between 2007 and 2014. Six
      (3.3%) patients died as a result AP. Six cases of fungal peritonitis were
      reported. AP rate has decreased from 1 episode/29.7 PD-months in 2007 to 1/43.7
      PD-months in 2014. Ninety-nine (55%) patients had single AP while 81 (45%)
      patients had 2 episodes or more (multiple AP). Patients on automated PD carried a
      higher risk of developing multiple AP [odds ratio (OR) = 1.46, 95% confidence
      interval (CI): 1.01-1.71]. The first episode of AP caused by Gram-positive cocci
      carried a significant risk of multiple AP (OR = 4.3, 95 % CI: 2.2-8.2). Negative
      culture AP carried a significant protective role from multiple AP (OR = 0.35, 95%
      CI: 0.19-0.66). Most deaths occurred with the first episode of AP (4 out of 6).
      In this 8-year follow-up, epidemiologic study from Qatar, fungal peritonitis and
      mortality rate were very low, AP rate improved overall, multiple AP was prevalent
      (45%), and its risk increases with Gram-positive cocci infections. Our results
      signify the importance of implementing more efficient care bundles to prevent
      multiple AP.

PMID- 29456214
TI  - Outcome of renal transplant recipients with cytomegalovirus and BK polyomavirus
      co-infection nephropathy.
AB  - Reactivation of cytomegalovirus (CMV) and BK polyomavirus (BKV) can result in
      virus-associated tubulointerstitial nephritis in renal allografts. All those
      renal biopsies reported as viral cytopathic were isolated and examined by two
      independent renal histopathologists from our institute and classified as CMV,
      BKV, and CMV-BKV coinfection-associated viral cytopathic changes with
      confirmation through polymerase chain reaction technology in either serum or
      urine or both. All twenty patients were categorized as 10 in CMV, four in BKV,
      and six were in CMV-BKV coinfection. One patient each had received antithymocyte
      globulin and basiliximab as induction all patients received triple-drug
      immunosuppression. The mean graft survival was 69, 61, and 59 months in CMV, BKV,
      and CMV-BKV coinfection group, respectively. At the end of the study period, 10
      (50%) patients died. 1-, 3-and 5-year patient survival was 94%, 88% and 76% among
      CMV group, 75%, 75% and 50% in BKV group, and 96%, 83% and 62%, in CMV-BKV
      coinfection group (P = 0.157). CMV and BK virus are not so common infections in
      postrenal transplant patients yet an important cause of graft dysfunction.
      Coinfection did not pose an increased risk for acute rejection or patients and
      death-censored and uncensored graft survival among compared groups.

PMID- 29456215
TI  - Comparison of survival between dialysis patients with incident high-flux
      hemodialysis versus on-line hemodiafiltration: A single center experience in
      Saudi Arabia.
AB  - Conventional hemodialysis (HD) is the most common treatment modality used for
      renal replacement therapy. The concept of HD is based on the diffusion of solutes
      across a semipermeable membrane. Hemofiltration (HF) is based on convective
      transport of solutes; hemodiafiltration (HDF) is based on combined convective and
      diffusive therapies. Data about survival benefit of on-line HDF (OL-HDF) over
      high-flux HD (HF-HD) is conflicting. We conducted this study to investigate if
      there is a survival difference between the two treatment modalities. This study
      is a retrospective, single-center study in which 78 patients were screened; 18
      were excluded and 60 patients were analyzed. The study patients were aged 47.5 +/
      20.7 years, 33 patients (55%) were on HF-HD, and 27 patients (45%) were on OL
      HDF. A total of 24 patients (40%) of both groups were diabetic and, the mean
      duration on dialysis was 43.5 +/-21.3 months in the HF-HD group and 41.2 +/- 22.0
      months in the OL-HDF group. The mean substitution volume for OL-HDF was 22.3 +/-
      2.5 L. Survival was 73% [95%, confidence interval (CI) 60-84] in the HF-HD group
      and 65% (95%, CI 54-75) in the OL-HDF group by the end of the study period. The
      unadjusted hazard ratio (HR) with 95% CI comparing HF-HD to high-volume
      postdilution OL-HDF was 0.78 (0.10-5.6; P = 0.810). Kaplan-Meier analysis for
      patient survival over five years showed no significant difference between the two
      modalities. Prospective controlled trials with a larger number of patients will
      be needed to assess the long-term clinical outcome of postdilution OL-HDF over HF
      HD.

PMID- 29456216
TI  - The cardiovascular risk factor profiles among end-stage renal failure patients
      treated with continuous ambulatory peritoneal dialysis and intermittent
      hemodialysis.
AB  - Cardiovascular (CV) event is the most common cause of death in dialysis patients.
      Both traditional and nontraditional CV risk factors related to malnutrition,
      inflammation, and anemia are commonly found in this population. This study was
      conducted to evaluate the burden factors of CV risk factors and its management in
      our regularly dialyzed patients. It was a single-center, cross-sectional analysis
      of prevalent intermittent hemodialysis (IHD) and continuous ambulatory peritoneal
      dialysis (CAPD) patients followed up in our hospital. Both the traditional and
      non-traditional CV risk factors were recorded and compared between the two
      groups. Eighty-eight patients were recruited. Forty-five were treated with CAPD
      and 43 patients were treated with IHD. The mean age was 49.5 +/- 15.17 years old
      and 54.5% were females. Eighty percent were Malay followed by Chinese (14.7%) and
      Indian (5.7%). Thirty-eight percent were hypertensive and 17% were diabetic. The
      mean age of CAPD patients was 48.9 +/- 16.9 compared to 50 +/- 13.5 years old for
      IHD patients (P > 0.05). The body mass index (BMI) of CAPD patients was 23.9
      kg/m2 versus 21.7 kg/m2 of the IHD (P = 0.04). The systolic and diastolic blood
      pressure of CAPD patients were 158 and 89 mm Hg in comparison to 141 and 72 mm Hg
      in IHD patients (P <0.001) and their total and low-density lipoprotein
      cholesterol level were 5.93 mmol/L and 3.84 mmol/L versus 4.79 mmol/L and 2.52
      mmol/L, respectively (P<=0.001). The CAPD patients were hyperglycemic more than
      IHD patients, although it was not statistically significant. All the
      nontraditional CV risk factors except serum albumin were comparable between the
      two groups. Serum albumin in CAPD patients was 35.5 g/L compared to 40.8 g/L in
      the IHD patients (P <0.001). In our prevalent dialysis-dependent patients, both
      traditional and non-traditional CV risk factors are common. Due to the prolonged
      and continuous glucose exposure from the peritoneal dialysis fluid, the CAPD
      patients had highly atherogenic serum, higher BMI, and intensified inflammation
      which pre-disposed them to higher CV events.

PMID- 29456217
TI  - Vascular access mortality and hospitalization among hemodialysis patients in
      Palestine.
AB  - Vascular access complications are common in patients with end-stage kidney
      disease who are receiving maintenance hemodialysis (HD) and are responsible for
      an enormous burden of morbidity and mortality among these patients. Differences
      in the all-cause mortality rate and hospitalization between dialysis catheter use
      and arteriovenous (AV) vascular access use have not been documented in our HD
      population. We performed a 12-month prospective analysis of our HD patients from
      four dialysis centers. We examined all-cause mortality and hospitalization in
      patients being dialyzed through HD catheters as compared to patients with AV
      access. A total of 382 patients were included in the study. Of these, 88 had
      catheters and 294 had AV accesses. Seventy-eight percent of all catheters were
      temporary nontunneled dialysis catheters. The overall gross mortality rate for
      all patients was 14.7%. Gross mortality was significantly lower among AV access
      group compared to the catheter group (12.2% vs. 22.7%; P = 0.015). Catheter use
      was associated with a relative hazard ratio (HR) of 1.85 [95% confidence interval
      (CI), 1.13-3.03] compared with use of an AV access. Hospitalization rate was also
      significantly lower among patients with AV access versus patients who used
      catheters (27.6% vs. 46.6%; P = 0.006). The risk of hospitalization was also
      higher in catheter users with a relative HR of 1.69 (95% CI, 1.26-2.26) compared
      with use of AV access. In our HD population where the majority of catheters were
      temporary nontunneled catheters, dialysis catheter use was associated with higher
      mortality and increased hospitalization rates compared with AV access. These
      results emphasize the urgent need to minimize the use of dialysis catheters, in
      order to reduce mortality and hospitalization rates among HD patients.

PMID- 29456218
TI  - Renal anemia syndromes in iraqi hemodialysis patients according to iron status.
AB  - Anemia is common in patients on hemodialysis (HD). Adequate iron stores are
      essential for achieving the best hemoglobin level through maximum benefit from
      erythropoiesis-stimulating agents (ESA). Decreased iron stores or decreased
      availability of iron are the most common reasons for resistance to the effect of
      these agents. Our objective was to categorize a group of Iraqi HD patients
      according to absolute or functional iron deficiency anemia (IDA); this study was
      conducted in the HD unit of the Baghdad Teaching Hospital from October 2012 to
      January 2013. Seventy prevalent adult HD Iraqi patients were enrolled. All
      patients were tested for full blood counts and iron parameters. They were
      categorized as nonanemic and those with absolute or functional iron deficiency.
      The patients were also tested for serum albumin, C-reactive protein (CRP),
      parathyroid hormone, and serum hepcidin levels. Data were expressed as mean +/-
      standard deviation, and frequencies (number) and proportions (%). The mean age of
      the study group was 49.8 +/- 12.3 years. Diabetes was the primary cause of end
      stage renal disease, seen in 30 patients (42.8%). Majority of the HD patients
      were anemic, [51 (82.9%)] and among them, 39 (76.4%), had functional IDA. The
      mean serum iron, serum ferritin, and transferrin saturation were significantly
      higher in patients with functional IDA than those with absolute IDA (P <0.05).
      The mean highly sensitive CRP, parathormone and hepcidin values were also
      significantly higher in functional IDA patients than in those with absolute IDA
      and the nonanemic group (P <0.05). More than half of the study patients had
      functional IDA, and this can explain ESA hyporesponsiveness. This is besides the
      interplay of other factors including inflammation, inadequate dialysis, and
      secondary hyperparathyroidism. It is essential to diagnose functional IDA early,
      before the initiation of unnecessary iron therapy.

PMID- 29456219
TI  - Descriptive analysis of glomerulonephritis by histological type and their
      progression among adults in a tertiary care center in Sri Lanka.
AB  - Prevalence of different glomerulonephritides and their clinical course vary
      geographically. Our objectives are to assess the prevalence of different
      histological types of glomerulonephritis (GN) based on the light microscopic
      histology and to assess their progression according to histological type. A
      retrospective cross-sectional study was carried out among adult patients (>18
      years) with a histological diagnosis of GN at the University Professorial Unit
      over a period of six months. Information including demographic data, renal biopsy
      findings, and progression of the disease through serum creatinine (SCr) level
      were collected through existing clinic records of consenting patients. Data were
      analyzed by Statistical Package for the Social Sciences. There were 109 patients
      (females = 90) with a mean age of 40.32 +/- 15.24 years. The most common
      histological type was focal segmental glomerulosclerosis (FSGS) in 27 (24.8%)
      followed by minimal change disease in 25 (22.9%), mesangioproliferative
      glomerulonephritis (MesPGN) in 18 (16.5%), membranoproliferative
      glomerulonephritis in six (5.5%), membranous glomerulonephritis in three patients
      (2.8%), and crescentic GN in one patient (0.9%). There was a statistically
      significant rise in SCr level at seven years from the initial presentation in the
      histological types; FSGS [P = 0.04; 95% confidence interval (CI) = 0.06-1.0] and
      MesPGN (P = 0.03; 95% CI = 0.3-0.9). Focal segmental glomerulosclerosis was the
      most common histology type in the population studied. There was a statistically
      significant progression of FSGS and MesPGN.

PMID- 29456220
TI  - Importance of renal biopsy in patients aged 60 years and older: Experience from a
      tertiary care hospital.
AB  - As the life expectancy is increasing, there is a rise in elderly population and
      consequent increase in the patients with renal disease. There is an inconsistency
      between clinical and histopathological diagnosis in elderly, and so renal biopsy
      is important in these patients to decide appropriate clinical management and
      prognosis. This study outlines the importance of renal biopsy in elderly and
      describes the clinical and pathologic spectrum of renal diseases in patient >=60
      years. All patients (age >=60 years) undergoing renal biopsies from January 2011
      to December 2014 were included in this retrospective study. The clinical
      presentation and biochemical findings were recorded, and the patients were
      grouped based on their clinical presentation. Renal biopsies were also evaluated.
      The mean age of patients was 67.7 +/- 6.4 years with a male:female ratio of 3:1.
      The most common clinical manifestation was nephrotic syndrome (37.4%) followed by
      rapidly progressive renal failure (RPRF) (20.6%). Amyloidosis and membranous
      nephropathy were two most common diagnoses in patients with nephrotic
      presentation whereas pauci-immune crescentic glomerulonephritis and cast
      nephropathy were common in patients presenting with RPRF. Clinical diagnosis
      differed from the histopathological diagnosis in 32% cases of nephrotic syndrome.
      There was good agreement between clinical diagnosis and histology in cases with
      RPRF. In 73% cases of elderly with (Type II) diabetes suspected of having
      nondiabetic renal disease clinically, renal biopsy showed evidence of diabetic
      nephropathy. Renal biopsy is essential in the diagnosis of renal diseases even in
      elderly. Amyloidosis and membranous nephropathy are common causes of nephrotic
      syndrome in elderly. Renal biopsy is very useful in diagnosing cast nephropathy
      and amyloidosis as they are not suspected clinically. It is also helpful in
      elderly diabetics without retinopathy to differentiate between diabetic and
      nondiabetic kidney diseases.

PMID- 29456221
TI  - Comparison between brief food frequency questionnaire and food record to assess
      the energy and protein intake of hemodialysis patients at Dr. Sardjito Hospital
      in Indonesia.
AB  - Dietary assessment is absolutely necessary to meet the dietary requirements of
      hemodialysis (HD) patients. A food record is the most commonly used method;
      however, it is not routinely performed. The weakness of this method is that it is
      burdensome for some respondents and requires more time to complete data entry.
      Meanwhile, the brief food frequency questionnaire (BFFQ) is a quicker and simpler
      method to assess individual dietary intake. We aimed to compare the BFFQ and food
      records as assessment methods of energy and protein intake for HD patient in Dr.
      Sardjito Hospital in Indonesia. This study was conducted on March to April 2015
      in HD Unit of Dr. Sardjito Hospital, Indonesia, as an observational study. This
      was a cross-sectional study. Data were collected from 103 patients, who were
      selected using a purposive sampling method. All participants' dietary intakes
      were assessed using a food record and the BFFQ to obtain total protein and energy
      intakes. Wilcoxon test was used for the statistical analysis. There was a
      significant difference (P <0.0001) between the methods used to assess energy
      intake in HD patients at Dr. Sardjito Hospital. However, there was no significant
      difference (P = 0.732) between the two methods used to assess protein intake
      among patients. This difference was caused by a missing list in the BFFQ about
      snacks that were usually consumed by patients as energy sources. The BFFQ can be
      used as a protein intake assessment tool in HD patients. However, the BFFQ is not
      suitable to assess energy intake in patients.

PMID- 29456222
TI  - Prevalence and risk factors of chronic kidney disease in Cote D'Ivoire: An
      analytic study conducted in the department of internal medicine.
AB  - Chronic kidney disease (CKD) has become a public health problem because of its
      increasing prevalence. The objective of this study was to describe the current
      profile of CKD in our working conditions. This is a descriptive retrospective
      study of patients admitted for CKD during the period from January 2010 to
      December 2014 in the Internal Medicine Department of the university hospital of
      Treichville in Abidjan. CKD was defined by a glomerular filtration rate below 60
      mL/min lasting for at least three months. We collected 252 cases of CKD out of
      3573 patients recorded during the study period, yielding a prevalence of 7%. The
      mean age was 39.6 +/- 14 years (15-83 years). We observed a male predominance
      (sex ratio 1.2:1). Of the CKD patients studied, 67.1% were hypertensive, 7.9%
      were diabetic, and 8.7% were positive for human immunodeficiency (HIV) virus. The
      CKD was Stage 3 in 2.4%, Stage 4 in 3.2%, and Stage 5 in 94.4% of the patients.
      The etiology of CKD was hypertension in 59.9% of cases, followed by chronic
      glomerulonephritis (25%), HIV infection (9.1%), and diabetes (4.8%). On bivariate
      analysis, hypertension was the cause of CKD in 48.8% of patients under 35 years,
      66.4% in patients between 35 and 64 years, and 85.4% in patients >=65 years (P =
      0.001). Chronic glomerulonephritis was the cause of CKD in 40.2% of patients
      under 35 years, in 14.3% between 35 and 64 years, and in 4.8% of patients >=65
      years (P = 0.0001). CKD is a common cause of hospitalization in our department.
      Patients generally consulted at the late stage of the disease. Risk factors are
      mainly hypertension, HIV infection, and diabetes.

PMID- 29456223
TI  - Knowledge and attitude toward organ donation among people in Lanja: A rural town
      in India.
AB  - Organ shortage is the greatest challenge facing the field of organ
      transplantation today. We aimed to study the attitude and knowledge toward body
      and organ donation among people in rural India. The present study was conducted
      in a rural town called Lanja, in the Konkan region of Maharashtra in India. A
      questionnaire covering demographic data, knowledge, and attitude of the
      participants was distributed to 400 students, middle-aged and senior citizens;
      91.5% of the respondents were aware about organ donation. Television (55.2%) and
      newspaper (45.8%) were the most popular sources of information. About 56.2% and
      32.8% believed that a healthy person and a cardiac dead person can be donors,
      respectively. Nearly 29.4% believed that a brain-dead person can be a donor and
      22.4% clearly stated as to be having no idea regarding the health status of a
      donor. Highest awareness was observed regarding eye donation (92%). High
      awareness was also observed regarding heart, kidney, and liver donations, that
      is, 71.1%, 61.2%, and 54.2%, respectively. Awareness regarding donation of other
      tissues and organs was poor. Only 46.8% believed that the family of the deceased
      person can give consent for organ donation if the donor had not signed the donor
      card. Awareness regarding both body and organ donation in rural India is high.
      However, there is lack of understanding regarding the concept of brain-death.
      Awareness regarding body and other organ and tissue donations besides eye,
      kidney, etc., needs further awareness drives.

PMID- 29456224
TI  - Alport's syndrome with focal segmental glomerulosclerosis lesion - Pattern to
      recognize.
AB  - The association between Alport's syndrome (AS) and focal segmental
      glomerulosclerosis (FSGS) in the same patient is complex and rarely reported. We
      report a case of a 42-year-old male presenting with proteinuria, microscopic
      hematuria, elevated serum creatinine and hypertension with unremarkable physical
      examination apart from obesity. The renal biopsy showed well-established FSGS
      pattern of injury with mild interstitial fibrosis and tubular atrophy, while the
      electron microscopic examination demonstrated glomerular basement membranes (GBM)
      changes compatible with AS. AS can be complicated by segmental glomerular
      scarring, which can mimic primary FSGS, while familial FSGS can result from
      mutations in collagen IV network of the GBM. This overlap can complicate
      histopathological interpretation of renal biopsy, which should be accompanied by
      mutational analysis for accurate diagnosis and proper therapeutic intervention.

PMID- 29456225
TI  - Perfused nonfunctioning renal allograft: Case report and review of the
      literature.
AB  - We report a case of very early postoperative iatrogenic dissection of common
      iliac artery (CIA), external iliac artery (EIA) causing acute ischemia of the
      right lower limb, and impairing the perfusion of a renal allograft. This was
      managed successfully by graft nephrectomy and interposition
      polytetrafluoroethylene grafting of the CIA and EIA with re-implantation of the
      kidney allograft and restoration of its perfusion and function, together with
      restoration of the lower limb circulation.

PMID- 29456226
TI  - Three cases of prune belly syndrome at the Lagos State University Teaching
      Hospital, Ikeja.
AB  - Prune belly syndrome (PBS) is a rare congenital disorder affecting 2.5 to
      3.8/100,000 live births worldwide. Our objective of this report is to describe
      clinical manifestation, laboratory, and radiological characteristics of PBS in
      our patients, to highlight the limitations to offering appropriate patient care
      due to parents demanding discharge against medical advice and the need to
      increase the awareness regarding this rare disease. We report three cases; all
      referred after birth with lax abdominal wall, congenital anomalies of kidney, and
      urinary tract. One of the patients had an absent right foot. They all had
      cryptorchidism, and in one, there was deranged renal function. The reported cases
      had both medical and radiological interventions to varying degrees. They all had
      an abdominal ultrasound which revealed varying degrees of hydronephrosis,
      hydroureters, and bladder changes. Voiding cystourethrogram showed vesicoureteric
      reflux in one of the reported cases. Urinary tract infections were appropriately
      treated with antibiotics based on sensitivity. PBS management in our setting
      remains a challenge because of strong cultural beliefs, and high rate of
      discharge against medical advice. Focus should be on parent education, early
      diagnosis, and multidisciplinary management approach.

PMID- 29456227
TI  - A case of renal granulomatosis with polyangiitis following intravesical bacillus
      Calmette-Guerin therapy.
AB  - Various adverse reactions may occur after intravesical bacillus Calmette-Guerin
      (BCG) therapy. Although the virulence of attenuated BCG is low, serious
      complications such as bacterial cystitis, bladder contractures, granulomatous
      prostatitis, epididymitis, orchitis, and systemic reactions such as fever and
      malaise have been described. Disseminated granulomatosis such as hepatitis and
      pneumonitis have also been described, but are rare. We report here the case of a
      67-year-old patient who presented with renal granulomatosis with polyangiitis
      following intravesical BCG therapy for superficial bladder tumor. The biological
      evaluation revealed the presence of perinuclear anti-neutrophil cytoplasmic
      antibodies with specificity for antimyeloperoxidase. Renal biopsy specimen
      revealed pauci-immune crescentic glomerulonephritis with segmental glomerular
      necrosis, presence of granulomas and no evidence of any caseating necrosis. He
      received antituberculosis drugs in addition to corticosteroids and
      cyclophosphamide without any improvement of the renal function.

PMID- 29456228
TI  - Suttonella indologenes peritonitis in a patient receiving continuous ambulatory
      peritoneal dialysis.
AB  - Suttonella indologenes is a Gram-negative, aerobic coccobacillus of
      Cardiobacteriaceae family and its natural habitat is the mucous membranes of the
      upper respiratory system. The literature includes limited number of case reports
      concerning fatal endocarditis due to infection in the prosthetic heart valves
      caused by the aforementioned microorganism. However, there is no information on
      extracardiac involvement due to this microorganism. Here, we present a
      peritonitis case caused by Suttonella indologenes in a patient receiving
      continuous ambulatory peritoneal dialysis.

PMID- 29456229
TI  - Page kidney: A rare but surgically treatable cause of hypertension.
AB  - The Page kidney is a rare phenomenon. External renal parenchymal compression is
      the culprit. We report two cases of young males with flank pain, renal mass, and
      hypertension with history of blunt abdominal trauma. Initially, hypertension was
      controlled by angiotensin-converting enzyme (ACE) inhibitors but gradually became
      refractory to medical treatment. Laparoscopic nephrectomy was performed in both
      patients. We emphasize the Page kidney as a cause of hypertension in young
      patients, presenting with flank pain and renal mass with or without complications
      of hypertension. Management is aimed to control blood pressure by ACE inhibitors,
      aspiration of the hematoma, open hematoma evacuation, or nephrectomy.

PMID- 29456231
TI  - Late-onset choreoathetotic syndrome following heart surgery in adults with end
      stage renal disease.
AB  - Choreoathetotic syndrome is a rare complication of open cardiac surgery that is
      seen usually in children after surgery for congenital cardiac anomalies. Here, we
      report two cases of adult patients with end-stage renal disease (ESRD) on regular
      hemodialysis who developed acute choreoathetotic syndrome few days after cardiac
      surgeries under cardiopulmonary bypass (CPB). Improvement was seen after an
      interval with complete resolution in one case. Investigations of the cause have
      been noncontributory. Long CPB time seems to be the main identified risk factor
      in these cases. One of the unusual features of our adult cases was the existence
      of ESRD. To the best of our knowledge, this is the first time this complication
      is described in association with ESRD although the role of this comorbidity in
      these cases is uncertain.

PMID- 29456230
TI  - Isolated renal involvement of cytomegalovirus inclusion disease in an infant.
AB  - Cytomegalovirus (CMV) is the most common cause of congenital infections in humans
      occurring in 1% of all liveborns. Symptomatic congenital CMV infection involves
      multiple systems and causes significant morbidity and mortality in newborns.
      Isolated CMV infection of the kidneys in a living infant has not been reported in
      literature. Here, we report an infant who presented only with renomegaly and
      renal biopsy showed extensive CMV inclusions. Serum and urine polymerase chain
      reaction for CMV were positive, and CMV involvement of other organs was ruled
      out. The child for treated with intravenous ganciclovir and is currently on
      follow-up. Cytomegalic inclusion disease involving only kidneys without other
      systems involvement can occur. The treatment protocol is unclear and long-term
      follow-up is needed.

PMID- 29456232
TI  - Seizure induced by tranexamic acid in a patient with chronic kidney disease on
      maintenance dialysis.
AB  - Tranexamic acid (TXA) is an antifibrinolytic agent commonly used to achieve
      hemostasis. However, there have been a few case reports suggesting that high-dose
      intravenous TXA has epileptogenic property. In patients with renal impairment,
      even administering the usual recommended dose of TXA can induce seizure episodes.
      We present here a patient on hemodialysis who developed seizures after receiving
      two doses of TXA over 5 h period.

PMID- 29456233
TI  - Recurrent episodic myoglobinuric acute kidney injury as presenting manifestation
      of idiopathic polymyositis.
AB  - Polymyositis (PM) is a rare heterogeneous group of disorders with frequent
      multisystem involvement including uncommon renal manifestations. Acute kidney
      injury (AKI) as the primary manifestation of PM is extremely rare. Herein, we
      report a case of recurrent episodic AKI in an adult female who was subsequently
      diagnosed to have PM.

PMID- 29456234
TI  - Acute cellular rejection with coexisting tuberculous interstitial nephritis in
      renal allograft.

PMID- 29456235
TI  - Second delivery for a woman on hemodialysis: Prospects for the mother and the
      children.

PMID- 29456236
TI  - Scleroderma renal crisis.

PMID- 29456237
TI  - Bisphosphonate-related osteonecrosis of the jaw in a chronic hemodialysis
      patient.

PMID- 29456238
TI  - Remote Ischemic Postconditioning (RIPC) of the Upper Arm Results in Protection
      from Cardiac Ischemia-Reperfusion Injury Following Primary Percutaneous Coronary
      Intervention (PCI) for Acute ST-Segment Elevation Myocardial Infarction (STEMI).
AB  - BACKGROUND The aim of this study was to evaluate the role of remote ischemic
      postconditioning (RIPC) of the upper arm on protection from cardiac ischemia
      reperfusion injury following primary percutaneous coronary intervention (PCI) in
      patients with acute ST-segment elevation myocardial infarction (STEMI). MATERIAL
      AND METHODS Eighty patients with STEMI were randomized into two groups: primary
      PCI (N=44) and primary PCI+RIPC (N=36). RIPC consisted of four cycles of 5
      minutes of occlusion and five minutes of reperfusion by cuff inflation and
      deflation of the upper arm, commencing within one minute of the first PCI balloon
      dilatation. Peripheral venous blood samples were collected before PCI and at 0.5,
      8, 24, 48, and 72 hours after PCI. Levels of creatine kinase-MB (CK-MB), serum
      creatinine (Cr), nitric oxide (NO), and stromal cell-derived factor-1alpha (SDF
      1alpha) were measured. The rates of acute kidney injury (AKI) and the estimated
      glomerular filtration rate (eGFR) were calculated. RESULTS Patients in the
      primary PCI+RIPC group, compared with the primary PCI group, had significantly
      lower peak CK-MB concentrations (P<0.01), a significantly increased left
      ventricular ejection fraction (LVEF) (P=0.01), a significantly lower rate of AKI
      (P<0.01) a significantly increased eGFR (P<0.01), and decreased area under the
      curve (AUC) of CK-MB, NO and SDF-1alpha. CONCLUSIONS RIPC of the upper arm
      following primary PCI in patients with acute STEMI might provide cardiac and
      renal protection from ischemia-reperfusion injury via the actions of SDF-1alpha,
      and NO.

PMID- 29456239
TI  - A Rare Presentation of Cryptococcal Meningitis and Cerebellitis in an Asplenic
      Patient, Seronegative for Human Immunodeficiency Virus (HIV).
AB  - BACKGROUND Cryptococcal meningitis in patients who are seronegative for the human
      immunodeficiency virus (HIV) and in patients who are splenectomized is rare. This
      report is an unusual case of meningeal and cerebellar infection due to the
      encapsulated yeast, Cryptococcus neoformans, which has not previously been
      associated with asplenia. CASE REPORT A 65-year-old HIV-negative patient with a
      previous splenectomy, presented with a three-day history of fever, vomiting, and
      headache. His symptoms progressed to generalized body aches, persistent fever,
      and neck stiffness. A lumbar puncture was performed, and cerebrospinal fluid
      (CSF) culture grew Cryptococcus neoformans. Treatment commenced with intravenous
      amphotericin B and flucytosine. The patient required serial lumbar punctures due
      to persistent raised intracranial pressure (ICP). Magnetic resonance imaging
      (MRI) of the brain showed acute meningitis and cerebellitis. Antimicrobial
      therapy and CSF drainage resulted in clinical improvement.  CONCLUSIONS The
      occurrence of meningeal and cerebellar cryptococcosis in an asplenic patient is
      rare, and few cases have been previously reported. This case report highlights
      the possibility of invasive cryptococcal infection, or cryptococcosis, in
      asplenic individuals in the absence of HIV infection.

PMID- 29456240
TI  - Novel synthetic bisindolylmaleimide alkaloids inhibit STAT3 activation by binding
      to the SH2 domain and suppress breast xenograft tumor growth.
AB  - Signal transducer and activator of transcription 3 (STAT3) is constitutively
      activated in malignant tumors and plays important roles in multiple aspects of
      cancer aggressiveness. Thus, targeting STAT3 promises to be an attractive
      strategy for the treatment of advanced metastatic tumors. Bisindolylmaleimide
      alkaloid (BMA) has been shown to have anti-cancer activities and was thought to
      suppress tumor cell growth by inhibiting protein kinase C. In this study, we show
      that a newly synthesized BMA analog, BMA097, is effective in suppressing tumor
      cell and xenograft growth and in inducing spontaneous apoptosis. We also provide
      evidence that BMA097 binds directly to the SH2 domain of STAT3 and inhibits STAT3
      phosphorylation and activation, leading to reduced expression of STAT3 downstream
      target genes. Structure activity relationship analysis revealed that the
      hydroxymethyl group in the 2,5-dihydropyrrole-2,5-dione prohibits STAT3
      inhibitory activity of BMA analogs. Altogether, we conclude that the synthetic
      BMA analogs may be developed as anti-cancer drugs by targeting and binding to the
      SH2 domain of STAT3 and inhibiting the STAT3 signaling pathway.

PMID- 29456242
TI  - Bacterial pathogenesis: Channelling the host epigenome.

PMID- 29456241
TI  - Ecology and evolution of Mycobacterium tuberculosis.
AB  - Tuberculosis (TB) is the number one cause of human death due to an infectious
      disease. The causative agents of TB are a group of closely related bacteria known
      as the Mycobacterium tuberculosis complex (MTBC). As the MTBC exhibits a clonal
      population structure with low DNA sequence diversity, methods (such as multilocus
      sequence typing) that are applied to more genetically diverse bacteria are
      uninformative, and much of the ecology and evolution of the MTBC has therefore
      remained unknown. Owing to recent advances in whole-genome sequencing and
      analyses of large collections of MTBC clinical isolates from around the world,
      many new insights have been gained, including a better understanding of the
      origin of the MTBC as an obligate pathogen and its molecular evolution and
      population genetic characteristics both within and between hosts, as well as many
      aspects related to antibiotic resistance. The purpose of this Review is to
      summarize these recent discoveries and discuss their relevance for developing
      better tools and strategies to control TB.

PMID- 29456244
TI  - A new piece in the microbiome puzzle.

PMID- 29456243
TI  - Hopanoid lipids: from membranes to plant-bacteria interactions.
AB  - Lipid research represents a frontier for microbiology, as showcased by hopanoid
      lipids. Hopanoids, which resemble sterols and are found in the membranes of
      diverse bacteria, have left an extensive molecular fossil record. They were first
      discovered by petroleum geologists. Today, hopanoid-producing bacteria remain
      abundant in various ecosystems, such as the rhizosphere. Recently, great progress
      has been made in our understanding of hopanoid biosynthesis, facilitated in part
      by technical advances in lipid identification and quantification. A variety of
      genetically tractable, hopanoid-producing bacteria have been cultured, and tools
      to manipulate hopanoid biosynthesis and detect hopanoids are improving. However,
      we still have much to learn regarding how hopanoid production is regulated, how
      hopanoids act biophysically and biochemically, and how their production affects
      bacterial interactions with other organisms, such as plants. The study of
      hopanoids thus offers rich opportunities for discovery.

PMID- 29456245
TI  - Animal models of monoclonal immunoglobulin-related renal diseases.
AB  - The renal deposition of monoclonal immunoglobulins can cause severe renal
      complications in patients with B cell and plasma cell lymphoproliferative
      disorders. The overproduction of a structurally unique immunoglobulin can
      contribute to the abnormal propensity of monoclonal immunoglobulins to aggregate
      and deposit in specific organs. A wide range of renal diseases can occur in
      multiple myeloma or monoclonal gammopathy of renal significance, including
      tubular and glomerular disorders with organized or unorganized immunoglobulin
      deposits. The development of reliable experimental models is challenging owing to
      the inherent variability of immunoglobulins and the heterogeneity of the
      pathologies they produce. However, although imperfect, animal models are
      invaluable tools to understand the molecular pathogenesis of these diseases, and
      advances in creating genetically modified animals might provide novel approaches
      to evaluate innovative therapeutic interventions. We discuss the strategies
      employed to reproduce human monoclonal immunoglobulin-induced kidney lesions in
      animal models, and we highlight their advantages and shortcomings. We also
      discuss how these models have affected the management of these deposition
      diseases and might do so in the future. Finally, we discuss hypotheses that
      explain some limitations of the various models, and how these models might
      improve our understanding of other nephropathies without immunoglobulin
      involvement that have similar pathogenic mechanisms.

PMID- 29456248
TI  - Genetic variation: Putting causal variants on the map.

PMID- 29456247
TI  - B cells are the predominant mediators of early systemic viral dissemination
      during rectal LCMV infection.
AB  - Determining the magnitude of local immune response during mucosal exposure to
      viral pathogens is critical to understanding the mechanism of viral pathogenesis.
      We previously showed that vaginal inoculation of lymphocytic choriomeningitis
      virus (LCMV) fails to induce a robust innate immune response in the lower female
      reproductive tract (FRT), allowing high titer viral replication and a delay in T
      cell-mediated viral control. Despite this immunological delay, LCMV replication
      remained confined mainly to the FRT and the draining iliac lymph node. Here, we
      show that rectal infection with LCMV triggers type I/III interferon responses,
      followed by innate immune activation and lymphocyte recruitment to the colon. In
      contrast to vaginal exposure, innate immunity controls LCMV replication in the
      colon, but virus rapidly disseminates systemically. Virus-induced inflammation
      promotes the recruitment of LCMV target cells to the colon followed by splenic
      viral dissemination by infected B cells, and to a lesser extent by CD8 T cells.
      These findings demonstrate major immunological differences between vaginal and
      rectal exposure to the same viral pathogen, highlighting unique risks associated
      with each of these common routes of sexual viral transmission.

PMID- 29456249
TI  - RNA: Follow the SINE for nuclear localization.

PMID- 29456250
TI  - Paediatric genomics: diagnosing rare disease in children.
AB  - This corrects the article DOI: 10.1038/nrg.2017.116.

PMID- 29456251
TI  - Tonometers-which one should I use?
AB  - Although several factors are known to play a role in the development and
      progression of glaucoma, intraocular pressure (IOP) remains the only modifiable
      risk factor. Medical and surgical treatments for glaucoma both aim to reduce IOP
      to minimize disease progression. Tonometry is therefore an essential element of
      the ophthalmological exam. There are several types of tonometers available
      currently. These range from well-established instruments that have been in
      clinical use for decades to new devices, which are the result of recent
      technological advances. The various instruments have advantages and disadvantages
      that affect their suitability for a given setting, purpose, and patient
      population. In this review, we aim to describe the most commonly available
      tonometers today along with their advantages, disadvantages, and applicability.

PMID- 29456246
TI  - Mitochondrial dysfunction in diabetic kidney disease.
AB  - Globally, diabetes is the leading cause of chronic kidney disease and end-stage
      renal disease, which are major risk factors for cardiovascular disease and death.
      Despite this burden, the factors that precipitate the development and progression
      of diabetic kidney disease (DKD) remain to be fully elucidated. Mitochondrial
      dysfunction is associated with kidney disease in nondiabetic contexts, and
      increasing evidence suggests that dysfunctional renal mitochondria are
      pathological mediators of DKD. These complex organelles have a broad range of
      functions, including the generation of ATP. The kidneys are mitochondrially rich,
      highly metabolic organs that require vast amounts of ATP for their normal
      function. The delivery of metabolic substrates for ATP production, such as fatty
      acids and oxygen, is altered by diabetes. Changes in metabolic fuel sources in
      diabetes to meet ATP demands result in increased oxygen consumption, which
      contributes to renal hypoxia. Inherited factors including mutations in genes that
      impact mitochondrial function and/or substrate delivery may also be important
      risk factors for DKD. Hence, we postulate that the diabetic milieu and inherited
      factors that underlie abnormalities in mitochondrial function synergistically
      drive the development and progression of DKD.

PMID- 29456252
TI  - Normal tension glaucoma: review of current understanding and mechanisms of the
      pathogenesis.
AB  - Normal tension glaucoma (NTG) is an exception in the "glaucoma family" where the
      major risk factor, increased intraocular pressure, is missing. If not increased
      intraocular pressure, then what other causes can then lead to glaucomatous optic
      disc change and visual field loss in NTG? Several possibilities will be
      discussed. Among them a higher sensitivity to normal pressure, vascular
      dysregulation, an abnormally high translaminar pressure gradient and a
      neurodegenerative process due to impaired cerebrospinal fluid dynamics in the
      optic nerve sheath compartment. There are many excellent review papers published
      on normal tension glaucoma (NTG). The aim of this paper is therefore not to add
      another extensive review on NTG but rather to focus on and to discuss some
      possible mechanisms that are thought to be involved in the pathophysiology of NTG
      and to discuss the stronger and weaker aspects of each concept. The fact that
      several concepts exist suggests that NTG is still not very well understood and
      that no single mechanism on its own might adequately explain NTG.

PMID- 29456254
TI  - Far Ultraviolet Spectroscopy of Old Novae. II. RR Pic, V533 Her, and DI Lac.
AB  - The old novae V533 Her (Nova Her 1963), DI Lac (Nova Lac 1910), and RR Pic (Nova
      Pic 1891) are in (or near) their quiescent stage, following their nova
      explosions, and continue to accrete at a high rate in the aftermath of their
      explosions. They exhibit continua that are steeply rising into the FUV, as well
      as absorption lines and emission lines of uncertain origin. All three have Far
      Ultraviolet Spectroscopic Explorer (FUSE) spectra that offer not only higher
      spectral resolution but also wavelength coverage extending down to the Lyman
      Limit. For DI Lac, we have matched these FUSE spectra with existing archival
      International Ultraviolet Explorer spectral coverage to broaden the FUV
      wavelength coverage. We adopted the newly determined interstellar reddening
      corrections of Selvelli & Gilmozzi. The dereddened FUV spectra have been modeled
      with our grids of optically thick accretion disks and hot, NLTE white dwarf (WD)
      photospheres. The results of our modeling analysis indicate that the hot
      components in RR Pic and V533 Her are likely to be accretion disks with mass
      accretion rates of 10-8M? yr-1 and 10-9M? yr-1 respectively. However, the disk
      cannot produce the observed absorption lines. For the WD to be the source of the
      absorption lines in these two systems, it must be very hot, with a radius several
      times its expected size (because the WD in these systems is massive, it has a
      smaller radius). For DI Lac, we find the best fit to be a disk with M = 10-10M?
      yr-1 with a 30,000 K WD.

PMID- 29456255
TI  - FUSE Spectroscopy of the Accreting Hot Components in Symbiotic Variables.
AB  - We have conducted a spectroscopic analysis of the far ultraviolet archival
      spectra of four symbiotic variables, EG And, AE Ara, CQ Dra and RW Hya. RW Hya
      and EG And have never had a recorded outburst while CQ Dra and AE Ara have
      outburst histories. We analyze these systems while they are in quiescence in
      order to help reveal the physical properties of their hot components via
      comparisons of the observations with optically thick accretion disk models and
      NLTE model white dwarf photospheres. We have extended the wavelength coverage
      down to the Lyman Limit with FUSE spectra. We find that the hot component in RW
      Hya is a low mass white dwarf with a surface temperature of 160,000K. We re
      examine whether or not the symbiotic system CQ Dra is a triple system with a red
      giant transferring matter to a hot component made up of a cataclysmic variable in
      which the white dwarf has a surface temperature as low as ~20,000K. The very
      small size of the hot component contributing to the shortest wavelengths of the
      FUSE spectrum of CQ Dra agrees with an optically thick and geometrically thin
      (~4% of the WD surface) hot (~ 120, 000K) boundary layer. Our analysis of EG And
      reveals that its hot component is a hot, bare, low mass white dwarf with a
      surface temperature of 80-95,000K, with a surface gravity log(g) = 7.5. For AE
      Ara, we also find that a low gravity (log(g) ~ 6) hot (T ~ 130, 000K) WD accounts
      for the hot component.

PMID- 29456253
TI  - Delicate regulation of the cGAS-MITA-mediated innate immune response.
AB  - Although it has long been demonstrated that cytosolic DNA is a potent immune
      stimulant, it is only in recent years that the molecular mechanisms of DNA
      stimulated innate immune responses have emerged. Studies have established
      critical roles for the DNA sensor cyclic GMP-AMP synthase (cGAS) and the adapter
      protein MITA/STING in the innate immune response to cytosolic DNA or DNA viruses.
      Although the regulation of cGAS-MITA/STING-mediated signaling remains to be fully
      investigated, understanding the processes involved may help to explain the
      mechanisms of innate immune signaling events and perhaps autoinflammatory
      diseases and to provide potential therapeutic targets for drug intervention. In
      this review, we summarize recent progress on the regulation of the cGAS
      MITA/STING-mediated innate immune response to DNA viruses at the organelle
      trafficking, post-translational and transcriptional levels.

PMID- 29456256
TI  - Clustering the Orion B giant molecular cloud based on its molecular emission.
AB  - Context: Previous attempts at segmenting molecular line maps of molecular clouds
      have focused on using position-position-velocity data cubes of a single molecular
      line to separate the spatial components of the cloud. In contrast, wide field
      spectral imaging over a large spectral bandwidth in the (sub)mm domain now allows
      one to combine multiple molecular tracers to understand the different physical
      and chemical phases that constitute giant molecular clouds (GMCs). Aims: We aim
      at using multiple tracers (sensitive to different physical processes and
      conditions) to segment a molecular cloud into physically/chemically similar
      regions (rather than spatially connected components), thus disentangling the
      different physical/chemical phases present in the cloud. Methods: We use a
      machine learning clustering method, namely the Meanshift algorithm, to cluster
      pixels with similar molecular emission, ignoring spatial information. Clusters
      are defined around each maximum of the multidimensional Probability Density
      Function (PDF) of the line integrated intensities. Simple radiative transfer
      models were used to interpret the astrophysical information uncovered by the
      clustering analysis. Results: A clustering analysis based only on the J = 1 - 0
      lines of three isotopologues of CO proves suffcient to reveal distinct
      density/column density regimes (nH ~ 100 cm-3, ~ 500 cm-3, and > 1000 cm-3),
      closely related to the usual definitions of diffuse, translucent and high-column
      density regions. Adding two UV-sensitive tracers, the J = 1 - 0 line of HCO+ and
      the N = 1 - 0 line of CN, allows us to distinguish two clearly distinct chemical
      regimes, characteristic of UV-illuminated and UV-shielded gas. The UV-illuminated
      regime shows overbright HCO+ and CN emission, which we relate to a photochemical
      enrichment effect. We also find a tail of high CN/HCO+ intensity ratio in UV
      illuminated regions. Finer distinctions in density classes (nH ~ 7 * 103 cm-3 ~ 4
      * 104 cm-3) for the densest regions are also identified, likely related to the
      higher critical density of the CN and HCO+ (1 - 0) lines. These distinctions are
      only possible because the high-density regions are spatially resolved.
      Conclusions: Molecules are versatile tracers of GMCs because their line
      intensities bear the signature of the physics and chemistry at play in the gas.
      The association of simultaneous multi-line, wide-field mapping and powerful
      machine learning methods such as the Meanshift clustering algorithm reveals how
      to decode the complex information available in these molecular tracers.

PMID- 29456257
TI  - IRC +10 216 in 3-D: morphology of a TP-AGB star envelope.
AB  - During their late pulsating phase, AGB stars expel most of their mass in the form
      of massive dusty envelopes, an event that largely controls the composition of
      interstellar matter. The envelopes, however, are distant and opaque to visible
      and NIR radiation: their structure remains poorly known and the mass-loss process
      poorly understood. Millimeter-wave interferometry, which combines the advantages
      of longer wavelength, high angular resolution and very high spectral resolution
      is the optimal investigative tool for this purpose. Mm waves pass through dust
      with almost no attenuation. Their spectrum is rich in molecular lines and hosts
      the fundamental lines of the ubiquitous CO molecule, allowing a tomographic
      reconstruction of the envelope structure. The circumstellar envelope IRC +10 216
      and its central star, the C-rich TP-AGB star closest to the Sun, are the best
      objects for such an investigation. Two years ago, we reported the first detailed
      study of the CO(2-1) line emission in that envelope, made with the IRAM 30-m
      telescope. It revealed a series of dense gas shells, expanding at a uniform
      radial velocity. The limited resolution of the telescope (HPBW 11") did not allow
      us to resolve the shell structure. We now report much higher angular resolution
      observations of CO(2-1), CO(1-0), CN(2-1) and C4H(24-23) made with the SMA, PdB
      and ALMA interferometers (with synthesized half-power beamwidths of 3", 1" and
      0.3", respectively). Although the envelope appears much more intricate at high
      resolution than with an 11" beam, its prevailing structure remains a pattern of
      thin, nearly concentric shells. The average separation between the brightest CO
      shells is 16" in the outer envelope, where it appears remarkably constant. Closer
      to the star (< 40"), the shell pattern is denser and less regular, showing
      intermediary arcs. Outside the small (r < 0.3") dust formation zone, the gas
      appears to expand radially at a constant velocity, 14.5 km s-1, with small
      turbulent motions. Based on that property, we have reconstructed the 3-D
      structure of the outer envelope and have derived the gas temperature and density
      radial profiles in the inner (r < 25") envelope. The shell-intershell density
      contrast is found to be typically 3. The over-dense shells have spherical or
      slightly oblate shapes and typically extend over a few steradians, implying
      isotropic mass loss. The regular spacing of shells in the outer envelope supports
      the model of a binary star system with a period of 700 years and a near face-on
      elliptical orbit. The companion fly-by triggers enhanced episodes of mass loss
      near periastron. The densification of the shell pattern observed in the central
      part of the envelope suggests a more complex scenario for the last few thousand
      years.

PMID- 29456258
TI  - Modifying the Standard Disk Model for the Ultraviolet Spectral Analysis of Disk
      dominated Cataclysmic Variables. I. The Novalikes MV Lyrae, BZ Camelopardalis,
      and V592 Cassiopeiae.
AB  - The standard disk is often inadequate to model disk-dominated cataclysmic
      variables (CVs) and generates a spectrum that is bluer than the observed UV
      spectra. X-ray observations of these systems reveal an optically thin boundary
      layer (BL) expected to appear as an inner hole in the disk. Consequently, we
      truncate the inner disk. However, instead of removing the inner disk, we impose
      the no-shear boundary condition at the truncation radius, thereby lowering the
      disk temperature and generating a spectrum that better fits the UV data. With our
      modified disk, we analyze the archival UV spectra of three novalikes that cannot
      be fitted with standard disks. For the VY Scl systems MV Lyr and BZ Cam, we fit a
      hot inflated white dwarf (WD) with a cold modified disk ( [Formula: see text] ~ a
      few 10-9M? yr-1). For V592 Cas, the slightly modified disk ( [Formula: see text]
      ~ 6 * 10-9M? yr-1) completely dominates the UV. These results are consistent with
      Swift X-ray observations of these systems, revealing BLs merged with ADAF-like
      flows and/or hot coronae, where the advection of energy is likely launching an
      outflow and heating the WD, thereby explaining the high WD temperature in VY Scl
      systems. This is further supported by the fact that the X-ray hardness ratio
      increases with the shallowness of the UV slope in a small CV sample we examine.
      Furthermore, for 105 disk-dominated systems, the International Ultraviolet
      Explorer spectra UV slope decreases in the same order as the ratio of the X-ray
      flux to optical/UV flux: from SU UMa's, to U Gem's, Z Cam's, UX UMa's, and VY
      Scl's.

PMID- 29456259
TI  - Improvement of Electromagnetic Field Distributions Using High Dielectric Constant
      (HDC) Materials for CTL-Spine MRI: Numerical Simulations and Experiments.
AB  - This study investigates the use of pads with high dielectric constant (HDC)
      materials to alter electromagnetic field distributions in patients during
      magnetic resonance imaging (MRI). The study was performed with numerical
      simulations and phantom measurements. An initial proof-of-concept and validation
      was performed using a phantom at 64 MHz, showing increases of up to 10% in
      electromagnetic field when using distilled water as the high dielectric material.
      Additionally, numerical simulations with computational models of human anatomy
      were performed at 128 MHz. Results of these simulations using barium titanate
      (BaTiO3) beads showed a 61% increase of [Formula: see text] with a quadrature
      driven RF coil and a 64% increase with a dual-transmit array. The presence of the
      HDC material also allowed for a decrease of SAR up to twofold (e.g., peak 10 g
      averaged SAR from 54 to 22 W/kg with a quadrature driven RF coil and from 27 to
      22 W/kg with a dual-transmit array using CaTiO3 powder at 128 MHz). The results
      of this study show that the use of HDC pads at 128 MHz for MRI spine applications
      could result in improved magnetic fields within the region of interest, while
      decreasing SAR outside the region.

PMID- 29456260
TI  - RF Safety Evaluation of a Breast Tissue Expander Device for MRI: Numerical
      Simulation and Experiment.
AB  - This study describes the MRI-related radio frequency (RF) safety evaluation of
      breast tissue expander devices to establish safety criteria. Numerical
      simulations and experimental measurements were performed at 64 MHz with a gel
      phantom containing a breast expander. Additionally, computational modeling was
      performed (64 and 128 MHz) with an adult female model, containing a virtually
      implanted breast tissue expander device for four imaging landmark positions. The
      presence of the breast tissue expander device led to significant alterations in
      specific absorption rate (SAR) and|B1+|distributions. The main source of SAR
      alterations with the use of the breast expander device was the saline-filled
      pouch of the expander. Conversely, the variation of RF magnetic field (B1+) was
      mainly caused by the metallic port. The measured values of electric field
      magnitude did not increase significantly due to the introduction of the expander
      device. The maximum 1g- or 10g-averaged SAR values in tissues near the implant
      were lower than those expected in other regions of the patient body with
      normalization of both|B1+|equal to 2 MUT at the coil isocenter and whole body
      averaged SAR equal to 4W/kg.

PMID- 29456261
TI  - Insights into Activation of Cobalt Pre-Catalysts for C(sp2)-H Functionalization.
AB  - The activation of readily prepared, air-stable cobalt (II) bis(carboxylate) pre
      catalysts for the functionalization of C(sp2)-H bonds has been systematically
      studied. With the pyridine bis(phosphine) chelate, iPrPNP, treatment of 1
      (O2CtBu)2 with either B2Pin2 or HBPin generated cobalt boryl products. With the
      former, reduction to (iPrPNP)CoIBPin was observed while with the latter,
      oxidation to the cobalt(III) dihydride boryl, trans-(iPrPNP)Co(H)2BPin occurred.
      The catalytically inactive cobalt complex, Co[PinB(O2CtBu)2]2, accompanied
      formation of the cobalt-boryl products in both cases. These results demonstrate
      that the pre-catalyst activation from cobalt(II) bis(carboxylates), although
      effective and utilizes an air-stable precursor, is less efficient than activation
      of cobalt(I) alkyl or cobalt(III) dihydride boryl complexes, which are
      quantitatively converted to the catalytically relevant cobalt(I) boryl. Related
      cobalt(III) dihydride silyl and cobalt(I) silyl complexes were also synthesized
      from treatment of trans-(iPrPNP)Co(H)2BPin and (iPrPNP)CoPh with HSi(OEt)3,
      respectively. No catalytic silylation of arenes was observed with either complex
      likely due to the kinetic preference for reversible C-H reductive elimination
      rather than product- forming C-Si bond formation from cobalt(III). Syntheses of
      the cobalt(II) bis(carboxylate) and cobalt(I) alkyl of iPrPONOP, a pincer where
      the methylene spacers have been replaced by oxygen atoms, were unsuccessful due
      to deleterious P-O bond cleavage of the pincer. Despite their structural
      similarity, the rich catalytic chemistry of iPrPNP was not translated to iPrPONOP
      due to the inability to access stable cobalt precursors as a result of ligand
      decomposition via P-O bond cleavage.

PMID- 29456262
TI  - Mixed analytical-stochastic simulation method for the recovery of a Brownian
      gradient source from probability fluxes to small windows.
AB  - Is it possible to recover the position of a source from the steady-state fluxes
      of Brownian particles to small absorbing windows located on the boundary of a
      domain? To address this question, we develop a numerical procedure to avoid
      tracking Brownian trajectories in the entire infinite space. Instead, we generate
      particles near the absorbing windows, computed from the analytical expression of
      the exit probability. When the Brownian particles are generated by a steady-state
      gradient at a single point, we compute asymptotically the fluxes to small
      absorbing holes distributed on the boundary of half-space and on a disk in two
      dimensions, which agree with stochastic simulations. We also derive an expression
      for the splitting probability between small windows using the matched asymptotic
      method. Finally, when there are more than two small absorbing windows, we show
      how to reconstruct the position of the source from the diffusion fluxes. The
      present approach provides a computational first principle for the mechanism of
      sensing a gradient of diffusing particles, a ubiquitous problem in cell biology.

PMID- 29456263
TI  - Static and Intertemporal Household Decisions.
AB  - We discuss the most popular static and dynamic models of household behavior. Our
      main objective is to explain which aspects of household decisions different
      models can account for. Using this insight, we describe testable implications,
      identification results, and estimation findings obtained in the literature.
      Particular attention is given to the ability of different models to answer
      various types of policy questions.

PMID- 29456264
TI  - Hazardous Chemical Releases Occurring in School Settings, 14 States, 2008-2013.
AB  - Children are considered to be a vulnerabletion when it comes to exposures to
      hazardous substances. Schools, where children spend about one third of their day,
      are expected to be a safe environment. Yet, there are many hazardous substances
      in schools that can be inadvertently or intentionally released and harm the
      health of students and teachers alike. The purpose of this analysis is to
      characterize acute chemical release incidents in school settings and identify
      prevention practices. The acute chemical incident surveillance programs of the
      Agency for Toxic Substances and Disease Registry (ATSDR) captured 24,748 acute
      chemical release incidents from 14 states that participated during 2008-2013. We
      examined 335 of these incidents that occurred at schools. While only 1.3% (n =
      335) of all chemical incidents reported to ATSDR occurred in schools, these
      incidents represented a larger part of the total impacts, including 8.5% of
      incidents with persons injured, 5.7% of evacuations ordered, and 31.1% of people
      evacuated. Natural gas (21.8%) and mercury (18.2%) were the chemicals most
      frequently released. Collecting and analyzing data on acute school chemical
      releases allows stakeholders to target prevention initiatives and provide a
      school environment safe from these chemical exposures.

PMID- 29456265
TI  - Mental Well-Being Differences in Cohabitation and Marriage: The Role of Childhood
      Selection.
AB  - Prior studies have found that marriage benefits well-being, but cohabitation may
      provide similar benefits. An analysis of the British Cohort Study 1970, a
      prospective survey following respondents to age 42, examines whether partnerships
      in general, and marriage in particular, influence mental well-being in midlife.
      Propensity score matching indicates whether childhood characteristics are a
      sufficient source of selection to eliminate differences in well-being between
      those living with and without a partner and those cohabitating and married. The
      results indicate that matching on childhood characteristics does not eliminate
      advantages to living with a partner; however, matching eliminates differences
      between marriage and cohabitation for men and women more likely to marry. On the
      other hand, marriage may provide benefits to women less likely to marry unless
      they have shared children and are in long-lasting partnerships. Hence, childhood
      selection attenuates differences between cohabitation and marriage, except for
      women less likely to marry.

PMID- 29456266
TI  - Isotonic Regression under Lipschitz Constraint.
AB  - The pool adjacent violators (PAV) algorithm is an efficient technique for the
      class of isotonic regression problems with complete ordering. The algorithm
      yields a stepwise isotonic estimate which approximates the function and assigns
      maximum likelihood to the data. However, if one has reasons to believe that the
      data were generated by a continuous function, a smoother estimate may provide a
      better approximation to that function. In this paper, we consider the formulation
      which assumes that the data were generated by a continuous monotonic function
      obeying the Lipschitz condition. We propose a new algorithm, the Lipschitz pool
      adjacent violators (LPAV) algorithm, which approximates that function; we prove
      the convergence of the algorithm and examine its complexity.

PMID- 29456267
TI  - Inorganic carbon and oxygen dynamics in a marsh-dominated estuary.
AB  - We conducted a free-water mass balance-based study to address the rate of
      metabolism and net carbon exchange for the tidal wetland and estuarine portion of
      the coastal ocean and the uncertainties associated with this approach were
      assessed. We measured open water diurnal O2 and dissolved inorganic carbon (DIC)
      dynamics seasonally in a salt marsh-estuary in Georgia, U.S.A. with a focus on
      the marsh-estuary linkage associated with tidal flooding. We observed that the
      overall estuarine system was a net source of CO2 to the atmosphere and coastal
      ocean and a net sink for oceanic and atmospheric O2. Rates of metabolism were
      extremely high, with respiration (43 mol m-2 yr-1) greatly exceeding gross
      primary production (28 mol m-2 yr-1), such that the overall system was net
      heterotrophic. Metabolism measured with DIC were higher than with O2, which we
      attribute to high rates of anaerobic respiration and reduced sulfur storage in
      salt marsh sediments, and we assume substantial levels of anoxygenic
      photosynthesis. We found gas exchange from a flooded marsh is substantial,
      accounting for about 28% of total O2 and CO2 air-water exchange. A significant
      percentage of the overall estuarine aquatic metabolism is attributable to
      metabolism of marsh organisms during inundation. Our study suggests not rely on
      oceanographic stoichiometry to convert from O2 to C based measurements when
      constructing C balances for the coastal ocean. We also suggest eddy covariance
      measurements of salt marsh net ecosystem exchange underestimate net ecosystem
      production as they do not account for lateral DIC exchange associated with marsh
      tidal inundation.

PMID- 29456268
TI  - Evidence for ubiquitous preferential particle orientation in representative
      oceanic shear flows.
AB  - In situ measurements were undertaken to characterize particle fields in
      undisturbed oceanic environments. Simultaneous, co-located depth profiles of
      particle fields and flow characteristics were recorded using a submersible
      holographic imaging system and an acoustic Doppler velocimeter, under different
      flow conditions and varying particle concentration loads, typical of those found
      in coastal oceans and lakes. Nearly one million particles with major axis lengths
      ranging from ~14 MUm to 11.6 mm, representing diverse shapes, sizes, and aspect
      ratios were characterized as part of this study. The particle field consisted of
      marine snow, detrital matter, and phytoplankton, including colonial diatoms,
      which sometimes formed "thin layers" of high particle abundance. Clear evidence
      of preferential alignment of particles was seen at all sampling stations, where
      the orientation probability density function (PDF) peaked at near horizontal
      angles and coincided with regions of low velocity shear and weak turbulent
      dissipation rates. Furthermore, PDF values increased with increasing particle
      aspect ratios, in excellent agreement with models of spheroidal particle motion
      in simple shear flows. To the best of our knowledge, although preferential
      particle orientation in the ocean has been reported in two prior cases, our
      findings represent the first comprehensive field study examining this phenomenon.
      Evidence of nonrandom particle alignment in aquatic systems has significant
      consequences to aquatic optics theory and remote sensing, where perfectly random
      particle orientation and thus isotropic symmetry in optical parameters is
      assumed. Ecologically, chain-forming phytoplankton may have evolved to form large
      aspect ratio chains as a strategy to optimize light harvesting.

PMID- 29456269
TI  - Effect of settled diatom-aggregates on benthic nitrogen cycling.
AB  - The marine sediment hosts a mosaic of microhabitats. Recently it has been
      demonstrated that the settlement of phycodetrital aggregates can induce local
      changes in the benthic O2 distribution due to confined enrichment of organic
      material and alteration of the diffusional transport. Here, we show how this
      microscale O2 shift substantially affects benthic nitrogen cycling. In sediment
      incubations, the settlement of diatom-aggregates markedly enhanced benthic O2 and
      NO3- consumption and stimulated NO2- and NH4+ production. Oxygen microprofiles
      revealed the rapid development of anoxic niches within and underneath the
      aggregates. During 120 h following the settling of the aggregates,
      denitrification of NO3- from the overlying water increased from 13.5 MUmol m-2 h
      1 to 24.3 MUmol m-2 h-1, as quantified by 15N enrichment experiment.
      Simultaneously, N2 production from coupled nitrification-denitrification
      decreased from 33.4 MUmol m-2 h-1 to 25.9 MUmol m-2 h-1, probably due to
      temporary inhibition of the benthic nitrifying community. The two effects were of
      similar magnitude and left the total N2 production almost unaltered. At the
      aggregate surface, nitrification was, conversely, very efficient in oxidizing
      NH4+ liberated by mineralization of the aggregates. The produced NO3- was
      preferentially released into the overlying water and only a minor fraction
      contributed to denitrification activity. Overall, our data indicate that the
      abrupt change in O2 microdistribution caused by aggregates stimulates
      denitrification of NO3- from the overlying water, and loosens the coupling
      between benthic nitrification and denitrification both in time and space. The
      study contributes to expanding the conceptual and quantitative understanding of
      how nitrogen cycling is regulated in dynamic benthic environments.

PMID- 29456270
TI  - Thinking, Fast and Slow? Some Field Experiments to Reduce Crime and Dropout in
      Chicago.
AB  - We present the results of three large-scale randomized controlled trials (RCTs)
      carried out in Chicago, testing interventions to reduce crime and dropout by
      changing the decision making of economically disadvantaged youth. We study a
      program called Becoming a Man (BAM), developed by the nonprofit Youth Guidance,
      in two RCTs implemented in 2009-2010 and 2013-2015. In the two studies
      participation in the program reduced total arrests during the intervention period
      by 28-35%, reduced violent-crime arrests by 45-50%, improved school engagement,
      and in the first study where we have follow-up data, increased graduation rates
      by 12-19%. The third RCT tested a program with partially overlapping components
      carried out in the Cook County Juvenile Temporary Detention Center (JTDC), which
      reduced readmission rates to the facility by 21%. These large behavioral
      responses combined with modest program costs imply benefit-cost ratios for these
      interventions from 5-to-1 up to 30-to-1 or more. Our data on mechanisms are not
      ideal, but we find no positive evidence that these effects are due to changes in
      emotional intelligence or social skills, self-control or "grit," or a generic
      mentoring effect. We find suggestive support for the hypothesis that the programs
      work by helping youth slow down and reflect on whether their automatic thoughts
      and behaviors are well suited to the situation they are in, or whether the
      situation could be construed differently. JEL Codes: C91, C93, D03, D1, I24, I3,
      I32, K42.

PMID- 29456271
TI  - To Compare is to Despair? A Population-Wide Study of Neighborhood Composition and
      Suicide in Stockholm.
AB  - Neighborhood context can change the effect of a socio-demographic attribute on
      the risk of suicide. Eight hypotheses about the interactions between neighborhood
      composition, ethnicity, income, and socially disadvantaged propositions are
      proposed based on social support, social comparison, and social regulation
      mechanisms. They are tested with a population-based dataset of all adults (1.4
      million) who lived in the greater Stockholm area in the 1990s. On one hand,
      multilevel analysis shows that suicide risk increases with the level of affluence
      in one's neighborhood, particularly among individuals with low income. This
      supports the notion that income comparison can have negative consequences. On the
      other hand, social welfare recipients are less likely to commit suicide when
      there are other social welfare recipients in the neighborhood. Suicide risk among
      immigrants deceases with the proportion of co-ethnics in the neighborhood,
      confirming previous findings on social support and suicide. However, further
      analyses show that the protection effect of having co-ethnic neighbors is limited
      to immigrants from countries with low suicide rates. This study shows that
      administrative data can be used to examine neighborhood effects on rare outcomes.
      The findings are relevant to the contemporary trends towards rising income
      inequality and ethnic diversity.

PMID- 29456272
TI  - Political Ecologies of Global Health: Pesticide Exposure in Southwestern
      Ecuador's Banana Industry.
AB  - Pesticide exposure in Ecuador's banana industry reflects political economic and
      ecological processes that interact across scales to affect human health. We use
      this case study to illustrate opportunities for applying political ecology of
      health scholarship in the burgeoning field of global health. Drawing on an
      historical literature review and ethnographic data collected in Ecuador's El Oro
      province, we present three main areas where a political ecological approach can
      enrich global health scholarship: perceptive characterization of multi-scalar and
      ecologically entangled pathways to health outcomes; critical analysis of
      discursive dynamics such as competing scalar narratives; and appreciation of the
      environment-linked subjectivities and emotions of people experiencing globalized
      health impacts. Rapprochement between these fields may also provide political
      ecologists with access to valuable empirical data on health outcomes, venues for
      engaged scholarship, and opportunities to synthesize numerous insightful case
      studies and discern broader patterns.

PMID- 29456273
TI  - The Effects of Acute Cannabis Use on Nontraffic Injury Risk: Reviewing the
      Available Literature and Identifying Ways Forward.
AB  - Recent evidence has indicated that cannabis use before driving is associated with
      a modest but increased risk for traffic-related injuries. However, the question
      of whether recent cannabis use is associated with a greater risk for other types
      of injuries remains unanswered. Aiming to understand better how acute cannabis
      use might affect the risk for all causes of injury, we have summarized the
      limited data available in the literature on the risk of non-traffic injuries
      associated with recent cannabis use. Very few studies were able to provide
      estimate risks for all injuries or injuries other than those related to road
      traffic injuries, with the limited evidence available showing mixed findings. The
      only significant risk found (in only one study) suggests an inverse association
      between all injuries and cannabis use. Study designs are limited, and the
      majority of studies have neither data on acute cannabis use among injured
      individuals nor a valid control group for estimating injury risk attributable to
      cannabis. In conclusion, studies of the association between cannabis and non
      traffic injuries present several limitations, particularly regarding sampling
      strategies, injury risk assessment for different causes of injury, and a dose
      response risk relationship with injury. Further studies, incorporating better
      design for different causes of injury and drug testing, are required to reach
      firmer conclusions on the association between cannabis use and non-traffic injury
      risk.

PMID- 29456274
TI  - Maintaining disorder: the micropolitics of drugs policy in Iran.
AB  - This article analyses the ways in which the state 'treats' addiction among
      precarious drug (ab)users in Iran. While most Muslim-majority as well as some
      Western states have been reluctant to adopt harm reduction measures, the Islamic
      Republic of Iran has done so on a nationwide scale and through a sophisticated
      system of welfare intervention. Additionally, it has introduced devices of
      management of 'addiction' (the 'camps') that defy statist modes of punishment and
      private violence. What legal and ethical framework has this new situation
      engendered? And what does this new situation tell us about the governmentality of
      the state? Through a combination of historical analysis and ethnographic
      fieldwork, the article analyses the paradigm of government of the Iranian state
      with regard to disorder as embodied by the lives of poor drug (ab)users.

PMID- 29456275
TI  - Antimicrobial packaging based on E-polylysine bioactive film for the control of
      mycotoxigenic fungi in vitro and in bread.
AB  - : E-Poly-l-lysine (E-PL) is a cationic peptide with a broad-spectrum
      antimicrobial activity. This study investigates the use of E-PL as natural
      antimicrobial to inhibit fungal growth and to reduce aflatoxins (AFs) production.
      Antifungal activity of starch biofilms with different concentrations of E-Poly-l
      lysine (E-PL) was determined in solid medium against Aspergillus parasiticus (AFs
      producer) and Penicillium expansum. Then, biofilms were tested as antimicrobial
      devices for the preservation of bread loaf inoculated with A. parasiticus CECT
      2681 and P. expansum CECT 2278. Shelf life and AFs content were examined.
      Biofilms with concentrations of E-PL less than 1.6 mg/cm2 showed no fungal growth
      inhibition in solid medium, while the antifungal activity of the films with
      greater than 1.6 mg/cm2 of E-PL was dose dependent. The shelf life of bread
      inoculated with A. parasiticus was increased by 1 day with the use of films
      containing 1.6-6.5 mg E-PL/cm2, while shelf life of bread tainted with P.
      expansum was increased by 3 day with 6.5 mg E-PL/cm2. AFs production was greatly
      inhibited by E-PL biofilms (93-100%). Thus, E-PL biofilms could be potentially
      used as antimicrobial device during bread storage as a natural alternative to the
      synthetic preservatives. Practical applications: E-Polylysin is a natural
      substance from microbial metabolism. Polylysine has a function to prevent a
      microbe from proliferating by ionic adsorption in the microbe. E-polylysine has a
      wide antibacterial spectrum and has an obvious lethal effect on Gram-positive and
      Gram-negative bacteria, yeast, mold, viruses, etc. It has a good antibacterial
      effect on the Gram-negative bacteria E. coli and Salmonellae, which are difficult
      to control with other natural preservatives. E-Polylysine has already been used
      generally as a food additive in Japan, Korea and other part of world. In the
      United States, FDA has recognized the polylysine as a GRAS material. Considered
      the positive results obtained in the study, this compound could be used for the
      production of antimicrobial biofilms, applied as separator slices in the loaf
      bread production, to prevent the growth of the mycotoxigenic fungi A. parasiticus
      and P. expansum, contributing to reduce the use of the synthetically
      preservatives in bakery industry and also of the negative impact that these
      compounds could generate on the health of the end users.

PMID- 29456276
TI  - Effects of natural antimicrobials with modified atmosphere packaging on the
      growth kinetics of Listeria monocytogenes in ravioli at various temperatures.
AB  - : The objective of this study was to investigate the antimicrobial effects of
      cultured sugar/vinegar (CSV) blend and nisin to control the risk of Listeria
      monocytogenes in ready to cook (RTC) ravioli. Ravioli dough was prepared with
      0.1, 0.3, 0.5, 1% CSV blend and 0.1, 0.2, and 0.3% nisin. Inoculated spinach or
      artichoke raviolis with 2.0 +/- 0.5 log cfu/g of L. monocytogenes were packed
      aerobically or using modified atmosphere packaging (MAP), and then stored at 4,
      10, 17, and 24  degrees C for 60 days. Growth kinetic parameters of the observed
      data fit well to the Baranyi equation. Ravioli with spinach filling materials
      yielded a higher risk than that with artichoke. L. monocytogenes was able to
      survive in ravioli with artichoke, but did not grow. The addition of 1% CSV blend
      or 0.3% nisin in spinach ravioli with the combination of MAP effectively
      controlled the growth of L. monocytogenes at the temperature below 10  degrees C.
      The organoleptic quality of spinach ravioli was not also affected by the
      application of 1% CSV blend. Therefore, the CSV blend can be recommended to
      improve the microbial safety and quality of natural RTC ravioli at retail market.
      Practical applications: The risk of ravioli was affected by the filling materials
      of ravioli at retail market. Addition of 1% cultured sugar/vinegar blend in dough
      substantially contributes to the extension of shelf-life of MAP spinach raviolis.
      classification and regression tree analysis results indicate that refrigeration
      temperature is the main control factor to affect lag time and growth rate, while
      packaging method is critical for maximum population density.

PMID- 29456277
TI  - Differential Attention to Faces in Infant Siblings of Children with Autism
      Spectrum Disorder and Associations with Later Social and Language Ability.
AB  - A growing body of literature has begun to explore social attention in infant
      siblings of children with autism spectrum disorder (ASD) with hopes of
      identifying early differences that are associated with later ASD or other aspects
      of development. The present study used eye-tracking to familiar (mother) and
      unfamiliar (stranger) faces in two groups of 6-month-old infants: infants with no
      family history of ASD (low-risk controls; LRC), and infants at high risk for ASD
      (HRA), by virtue of having an older sibling with ASD. HRA infants were further
      characterized based on autism classification at 24 months or older as HRA- (HRA
      without an ASD outcome) or HRA+ (HRA with an ASD outcome). For time scanning
      faces overall, HRA+ and LRC showed similar patterns of attention, and this was
      significantly greater than in HRA-. When examining duration of time spent on eyes
      and mouth, all infants spent more time on eyes than mouth, but HRA+ showed the
      greatest amount of time looking at these regions, followed by LRC, then HRA-. LRC
      showed a positive association between 6-month attention to eyes and 18-month
      social-communicative behavior, while HRA- showed a negative association between
      attention to eyes at 6 months and expressive language at 18 months (all
      correlations controlled for non-verbal IQ; HRA- correlations held with and
      without the inclusion of the small sample of HRA+). Differences found in face
      scanning at 6 months, as well as associations with social communication at 18
      months, point to potential variation in the developmental significance of early
      social attention in children at low and high risk for ASD.

PMID- 29456278
TI  - Investigation of patterned and non-patterned poly(2,6-dimethyl 1,4-phenylene)
      oxide based anion exchange membranes for enhanced desalination and power
      generation in a microbial desalination cell.
AB  - Quaternary ammonium poly(2,6-dimethyl 1,4-phenylene oxide) (QAPPO) anion exchange
      membranes (AEMs) with topographically patterned surfaces were assessed in a
      microbial desalination cell (MDC) system. The MDC results with these QAPPO AEMs
      were benchmarked against a commercially available AEM. The MDC with the non
      patterned QAPPO AEM (Q1) displayed the best desalination rate (a reduction of
      salinity by 53 +/- 2.7%) and power generation (189 +/- 5 mW m- 2) when compared
      against the commercially available AEM and the patterned AEMs. The enhanced
      performance with the Q1 AEM was attributed to its higher ionic conductivity and
      smaller thickness leading to a reduced area specific resistance. It is important
      to note that Real Pacific Ocean seawater and activated sludge were used into the
      desalination chamber and anode chamber respectively for the MDC - which mimicked
      realistic conditions. Although the non-patterned QAPPO AEM displayed better
      performance over the patterned QAPPO AEMs, it was observed that the anodic
      overpotential was smaller when the MDCs featured QAPPO AEMs with larger lateral
      feature sizes. The results from this study have important implications for the
      continuous improvements necessary for developing cheaper and better performing
      membranes in order to optimize the MDC.

PMID- 29456279
TI  - Uncertainty Footprint: Visualization of Nonuniform Behavior of Iterative
      Algorithms Applied to 4D Cell Tracking.
AB  - Research on microscopy data from developing biological samples usually requires
      tracking individual cells over time. When cells are three-dimensionally and
      densely packed in a time-dependent scan of volumes, tracking results can become
      unreliable and uncertain. Not only are cell segmentation results often inaccurate
      to start with, but it also lacks a simple method to evaluate the tracking
      outcome. Previous cell tracking methods have been validated against benchmark
      data from real scans or artificial data, whose ground truth results are
      established by manual work or simulation. However, the wide variety of real-world
      data makes an exhaustive validation impossible. Established cell tracking tools
      often fail on new data, whose issues are also difficult to diagnose with only
      manual examinations. Therefore, data-independent tracking evaluation methods are
      desired for an explosion of microscopy data with increasing scale and resolution.
      In this paper, we propose the uncertainty footprint, an uncertainty
      quantification and visualization technique that examines nonuniformity at local
      convergence for an iterative evaluation process on a spatial domain supported by
      partially overlapping bases. We demonstrate that the patterns revealed by the
      uncertainty footprint indicate data processing quality in two algorithms from a
      typical cell tracking workflow - cell identification and association. A detailed
      analysis of the patterns further allows us to diagnose issues and design methods
      for improvements. A 4D cell tracking workflow equipped with the uncertainty
      footprint is capable of self diagnosis and correction for a higher accuracy than
      previous methods whose evaluation is limited by manual examinations.

PMID- 29456280
TI  - Analyzing survival curves at a fixed point in time for paired and clustered right
      censored data.
AB  - In clinical trials, information about certain time points may be of interest in
      making decisions about treatment effectiveness. Rather than comparing entire
      survival curves, researchers can focus on the comparison at fixed time points
      that may have a clinical utility for patients. For two independent samples of
      right-censored data, Klein et al. (2007) compared survival probabilities at a
      fixed time point by studying a number of tests based on some transformations of
      the Kaplan-Meier estimators of the survival function. However, to compare the
      survival probabilities at a fixed time point for paired right-censored data or
      clustered right-censored data, their approach would need to be modified. In this
      paper, we extend the statistics to accommodate the possible within-paired
      correlation and within-clustered correlation, respectively. We use simulation
      studies to present comparative results. Finally, we illustrate the implementation
      of these methods using two real data sets.

PMID- 29456281
TI  - Foster home integration as a temporal indicator of relational well-being.
AB  - This study sought to identify factors that contribute to the relational well
      being of youth in substitute care. Using data from the [BLIND] study, youth
      responded to a 9-item measure of positive home integration, a scale designed to
      assess the relational experiences of youth to their caregivers and their
      integration into the foster home. Data were collected from youth in six month
      intervals, for an 18-month period of time. Latent growth curve modeling
      procedures were employed to determine if child, family, and case characteristics
      influenced youth's home integration trajectories. Results suggest stability in
      youth reports of home integration over time; however, children who were older at
      the time of study enrollment and youth who experienced placement changes during
      the period of observation experienced decreased home integration during the 18
      month period. Results suggest youth's perspectives of home integration may in
      part be a function of the child's developmental stage and their experiences with
      foster care placement instability. Implications for practice and future research
      are discussed.

PMID- 29456282
TI  - Beta approximation of ratio distribution and its application to next generation
      sequencing read counts.
AB  - Paired sequencing data are commonly collected in genomic studies to control
      biological variation. However, existing data processing strategies suffer at low
      coverage regions, which are unavoidable due to the limitation of current
      sequencing technology. Furthermore, information contained in the absolute values
      of the read counts is commonly ignored. We propose a read count ratio
      processing/modification method, to not only incorporate information contained in
      the absolute values of paired counts into one variable, but also mitigate the
      discrete artifact, especially when both counts are small. Simulation shows that
      the processed variable fits well with a Beta distribution, thus providing an easy
      tool for down-stream inference analysis.

PMID- 29456283
TI  - La-Ce isotope measurements by multicollector-ICPMS.
AB  - The 138La-138Ce decay system (half-life 1.02 * 1011 years) is a potentially
      highly useful tool to unravel information about the timing of geological
      processes and about the interaction of geological reservoirs on earth,
      complementing information from the more popular 147Sm-143Nd and 176Lu-176Hf
      isotope systems. Previously published analytical protocols were limited to TIMS.
      Here we present for the first time an analytical protocol that employs MC-ICPMS,
      with an improved precision and sensitivity. To perform sufficiently accurate La
      Ce measurements, an efficient ion-chromatographic procedure is required to
      separate Ce from the other rare earth elements (REE) and Ba quantitatively. This
      study presents an improved ion-chromatographic procedure that separates La and Ce
      from rock samples using a three-step column separation. After REE separation by
      cation exchange, Ce is separated employing an Ln Spec column and selective
      oxidation. In the last step, a cation clean-up chemistry is performed to remove
      all remaining interferences. Our MC-ICPMS measurement protocol includes all
      stable Ce isotopes (136Ce, 138Ce, 140Ce and 142Ce), by employing a 1010 ohm
      amplifier for the most abundant isotope 140Ce. An external reproducibility of +/
      0.25epsilon-units (2 r.s.d) has been routinely achieved for 138Ce measurements
      for as little as 150-600 ng Ce, depending on the sample-skimmer cone combinations
      being used. Because the traditionally used JMC-304 Ce reference material is not
      commercially available anymore, a new reference material was prepared from AMES
      laboratory Ce metal (Cologne-AMES). In order to compare the new material with the
      previously reported isotopic composition of AMES material prepared at Mainz
      (Mainz-AMES), Cologne-AMES and JMC-304 were measured relative to each other in
      the same analytical session, demonstrating isotope heterogeneity between the two
      AMES and different JMC-304 batches used in the literature. To enable sufficiently
      precise age correction of radiogenic 138Ce and to perform isochron dating, a
      protocol was developed where La and Ce concentrations are determined by isotope
      dilution (ID), using an isotope tracer enriched in 138La and 142Ce. The new
      protocols were applied to determine the variations of Ce isotope compositions and
      La-Ce concentrations of certified geochemical reference materials (CRMs): BCR-2,
      BCR-1, BHVO-2, JR-1, JA-2, JB-3, JG-1, JR-1, JB-1b, AGV-1 and one in-house La
      Palma standard.

PMID- 29456284
TI  - Spatially-explicit model for assessing wild dog control strategies in Western
      Australia.
AB  - Large predators can significantly impact livestock industries. In Australia, wild
      dogs (Canis lupus familiaris, Canis lupus dingo, and hybrids) cause economic
      losses of more than AUD$40M annually. Landscape-scale exclusion fencing coupled
      with lethal techniques is a widely practiced control method. In Western
      Australia, the State Barrier Fence encompasses approximately 260,000km2 of
      predominantly agricultural land, but its effectiveness in preventing wild dogs
      from entering the agricultural region is difficult to evaluate. We conducted a
      management strategy evaluation (MSE) based on spatially-explicit population
      models to forecast the effects of upgrades to the Western Australian State
      Barrier Fence and several control scenarios varying in intensity and spatial
      extent on wild dog populations in southwest Western Australia. The model results
      indicate that populations of wild dogs on both sides of the State Barrier Fence
      are self-sustaining and current control practices are not sufficient to
      effectively reduce their abundance in the agricultural region. Only when a
      combination of control techniques is applied on a large scale, intensively and
      continuously are wild dog numbers effectively controlled. This study identifies
      the requirement for addressing extant populations of predators within fenced
      areas to meet the objective of preventing wild dog expansion. This objective is
      only achieved when control is applied to the whole area where wild dogs are
      currently present within the fence plus an additional buffer of ~20 km. Our
      modelling focused on the use of baiting, trapping and shooting; however, we
      acknowledge that additional tools may also be applied. Finally, we recommend that
      a cost-benefit analysis be performed to evaluate the economic viability of an
      integrated control strategy.

PMID- 29456285
TI  - Improved power and long term performance of microbial fuel cell with Fe-N-C
      catalyst in air-breathing cathode.
AB  - Power output limitation is one of the main challenges that needs to be addressed
      for full-scale applications of the Microbial Fuel Cell (MFC) technology. Previous
      studies have examined electrochemical performance of different cathode electrodes
      including the development of novel iron based electrocatalysts, however the long
      term investigation into continuously operating systems is rare. This work aims to
      study the application of platinum group metals-free (PGM-free) catalysts
      integrated into an air-breathing cathode of the microbial fuel cell operating on
      activated sewage sludge and supplemented with acetate as the carbon energy
      source. The maximum power density up to 1.3 Wm-2 (54 Wm-3) obtained with iron
      aminoantipyrine (Fe-AAPyr) catalyst is the highest reported in this type of MFC
      and shows stability and improvement in long term operation when continuously
      operated on wastewater. It also investigates the ability of this catalyst to
      facilitate water extraction from the anode and electroosmotic production of clean
      catholyte. The electrochemical kinetic extraction of catholyte in the cathode
      chamber shows correlation with power performance and produces a newly synthesised
      solution with a high pH > 13, suggesting caustic content. This shows an active
      electrolytic treatment of wastewater by active ionic and pH splitting in an
      electricity producing MFC.

PMID- 29456286
TI  - Examining Thematic Similarity, Difference, and Membership in Three Online Mental
      Health Communities from Reddit: A Text Mining and Visualization Approach.
AB  - Objectives: Social media, including online health communities, have become
      popular platforms for individuals to discuss health challenges and exchange
      social support with others. These platforms can provide support for individuals
      who are concerned about social stigma and discrimination associated with their
      illness. Although mental health conditions can share similar symptoms and even co
      occur, the extent to which discussion topics in online mental health communities
      are similar, different, or overlapping is unknown. Discovering the topical
      similarities and differences could potentially inform the design of related
      mental health communities and patient education programs. This study employs text
      mining, qualitative analysis, and visualization techniques to compare discussion
      topics in publicly accessible online mental health communities for three
      conditions: Anxiety, Depression and Post-Traumatic Stress Disorder. Methods:
      First, online discussion content for the three conditions was collected from
      three Reddit communities (r/Anxiety, r/Depression, and r/PTSD). Second, content
      was pre-processed, and then clustered using the k-means algorithm to identify
      themes that were commonly discussed by members. Third, we qualitatively examined
      the common themes to better understand them, as well as their similarities and
      differences. Fourth, we employed multiple visualization techniques to form a
      deeper understanding of the relationships among the identified themes for the
      three mental health conditions. Results: The three mental health communities
      shared four themes: sharing of positive emotion, gratitude for receiving
      emotional support, and sleep- and work-related issues. Depression clusters tended
      to focus on self-expressed contextual aspects of depression, whereas the Anxiety
      Disorders and Post-Traumatic Stress Disorder clusters addressed more treatment-
      and medication-related issues. Visualizations showed that discussion topics from
      the Anxiety Disorders and Post-Traumatic Stress Disorder subreddits shared more
      similarities to one another than to the depression subreddit. Conclusions: We
      observed that the members of the three communities shared several overlapping
      concerns (i.e., sleep- and work-related problems) and discussion patterns (i.e.,
      sharing of positive emotion and showing gratitude for receiving emotional
      support). We also highlighted that the discussions from the r/Anxiety and r/PTSD
      communities were more similar to one another than to discussions from the
      r/Depression community. The r/Anxiety and r/PTSD subreddit members are more
      likely to be individuals whose experiences with a condition are long-term, and
      who are interested in treatments and medications. The r/Depression subreddit
      members may be a comparatively diffuse group, many of whom are dealing with
      transient issues that cause depressed mood. The findings from this study could be
      used to inform the design of online mental health communities and patient
      education programs for these conditions. Moreover, we suggest that researchers
      employ multiple methods to fully understand the subtle differences when comparing
      similar discussions from online health communities.

PMID- 29456287
TI  - Gamers' insights into the phenomenology of normal gaming and game "addiction": A
      mixed methods study.
AB  - In response to calls for further research into the phenomenology of Internet
      gaming disorder (IGD), we used a community-engaged consensus development approach
      to evaluate how members of the "gamer culture" describe problematic gaming and
      the relationship of these descriptions to the proposed IGD criteria. Two focus
      groups of gamers were recruited at a video game convention. Participants were
      asked to submit suggestions for signs of game "addiction". Participants discussed
      and ranked the criteria in order of conceptual importance. The rankings were
      analyzed quantitatively, and then a multidisciplinary team compared the ranked
      criteria to the DSM-5 IGD proposed criteria. The strongest agreement between
      participants' rankings and IGD symptomatology was found for harms/functional
      impairment due to gaming, continued use despite problems, unsuccessful attempts
      to control gaming, and loss of interest in previous hobbies and entertainment.
      There was less support for other IGD criteria. Participants also offered new
      content domains. These findings suggest that collaborative knowledge-building
      approaches may help researchers and policymakers understand the characteristics
      and processes specific to problematic video game play and improve content
      validity of IGD criteria. Future efforts may benefit from multi-stakeholder
      approaches to refine IGD criteria and inform theory, measurement and
      intervention.

PMID- 29456288
TI  - Distributional learning of subcategories in an artificial grammar: Category
      generalization and subcategory restrictions.
AB  - There has been significant recent interest in clarifying how learners use
      distributional information during language acquisition. Many researchers have
      suggested that distributional learning mechanisms play a major role during
      grammatical category acquisition, since linguistic form-classes (like noun and
      verb) and subclasses (like masculine and feminine grammatical gender) are
      primarily defined by the ways lexical items are distributed in syntactic
      contexts. Though recent experimental work has affirmed the importance of
      distributional information for category acquisition, there has been little
      evidence that learners can acquire linguistic subclasses based only on
      distributional cues. Across two artificial grammar-learning experiments, we
      demonstrate that subclasses can be acquired from distributional cues alone. These
      results add to a body of work demonstrating rational use of distributional
      information to acquire complex linguistic structures.

PMID- 29456289
TI  - The Synergy Between PAV and AdaBoost.
AB  - Schapire and Singer's improved version of AdaBoost for handling weak hypotheses
      with confidence rated predictions represents an important advance in the theory
      and practice of boosting. Its success results from a more efficient use of
      information in weak hypotheses during updating. Instead of simple binary voting a
      weak hypothesis is allowed to vote for or against a classification with a
      variable strength or confidence. The Pool Adjacent Violators (PAV) algorithm is a
      method for converting a score into a probability. We show how PAV may be applied
      to a weak hypothesis to yield a new weak hypothesis which is in a sense an ideal
      confidence rated prediction and that this leads to an optimal updating for
      AdaBoost. The result is a new algorithm which we term PAV-AdaBoost. We give
      several examples illustrating problems for which this new algorithm provides
      advantages in performance.

PMID- 29456290
TI  - A new precipitation and drought climatology based on weather patterns.
AB  - Weather-pattern, or weather-type, classifications are a valuable tool in many
      applications as they characterize the broad-scale atmospheric circulation over a
      given region. This study analyses the aspects of regional UK precipitation and
      meteorological drought climatology with respect to a new set of objectively
      defined weather patterns. These new patterns are currently being used by the Met
      Office in several probabilistic forecasting applications driven by ensemble
      forecasting systems. Weather pattern definitions and daily occurrences are mapped
      to Lamb weather types (LWTs), and parallels between the two classifications are
      drawn. Daily precipitation distributions are associated with each weather pattern
      and LWT. Standardized precipitation index (SPI) and drought severity index (DSI)
      series are calculated for a range of aggregation periods and seasons. Monthly
      weather-pattern frequency anomalies are calculated for SPI wet and dry periods
      and for the 5% most intense DSI-based drought months. The new weather-pattern
      definitions and daily occurrences largely agree with their respective LWTs,
      allowing comparison between the two classifications. There is also broad
      agreement between weather pattern and LWT changes in frequencies. The new data
      set is shown to be adequate for precipitation-based analyses in the UK, although
      a smaller set of clustered weather patterns is not. Furthermore, intra-pattern
      precipitation variability is lower in the new classification compared to the
      LWTs, which is an advantage in this context. Six of the new weather patterns are
      associated with drought over the entire UK, with several other patterns linked to
      regional drought. It is demonstrated that the new data set of weather patterns
      offers a new opportunity for classification-based analyses in the UK.

PMID- 29456291
TI  - The role of semantic processing in reading Japanese orthographies: an
      investigation using a script-switch paradigm.
AB  - Research on Japanese reading has generally indicated that processing of the
      logographic script Kanji primarily involves whole-word lexical processing and
      follows a semantics-to-phonology route, while the two phonological scripts
      Hiragana and Katakana (collectively called Kana) are processed via a sub-lexical
      route, and more in a phonology-to-semantics manner. Therefore, switching between
      the two scripts often involves switching between two reading processes, which
      results in a delayed response for the second script (a script switch cost). In
      the present study, participants responded to pairs of words that were written
      either in the same orthography (within-script), or in two different Japanese
      orthographies (cross-script), switching either between Kanji and Hiragana, or
      between Katakana and Hiragana. They were asked to read the words aloud
      (Experiments 1 and 3) and to make a semantic decision about them (Experiments 2
      and 4). In contrast to initial predictions, a clear switch cost was observed when
      participants switched between the two Kana scripts, while script switch costs
      were less consistent when participants switched between Kanji and Hiragana. This
      indicates that there are distinct processes involved in reading of the two types
      of Kana, where Hiragana reading appears to bear some similarities to Kanji
      processing. This suggests that the role of semantic processing in Hiragana (but
      not Katakana) reading is more prominent than previously thought and thus,
      Hiragana is not likely to be processed strictly phonologically.

PMID- 29456292
TI  - CBM maze-scores as indicators of reading level and growth for seventh-grade
      students.
AB  - The technical adequacy of CBM maze-scores as indicators of reading level and
      growth for seventh-grade secondary-school students was examined. Participants
      were 452 Dutch students who completed weekly maze measures over a period of 23
      weeks. Criterion measures were school level, dyslexia status, scores and growth
      on a standardized reading test. Results supported the technical adequacy of maze
      scores as indicators of reading level and growth. Alternate-form reliability
      coefficients were significant and intermediate to high. Mean maze scores showed
      significant increase over time, students' growth trajectories differed, and
      students' initial performance levels (intercepts) and growth rates (slopes) were
      not correlated. Maze reading level and growth were related to reading level
      and/or growth on criterion measures. A nonlinear model provided a better fit for
      the data than a linear model. Implications for use of CBM maze-scores for data
      based decision-making are discussed.

PMID- 29456293
TI  - Critical review of elementary flows in LCA data.
AB  - Purpose: Elementary flows are essential components of data used for life cycle
      assessment. A standard list is not used across all sources, as data providers now
      manage these flows independently. Elementary flows must be consistent across a
      life cycle inventory for accurate inventory analysis and must correspond with
      impact methods for impact assessment. With the goal of achieving a global network
      of LCA databases, a critical review of elementary flow usage and management in
      LCA data sources was performed. Methods: Flows were collected in a standard
      template from various life cycle inventory, impact method, and software sources.
      A typology of elementary flows was created to identify flows by types such as
      chemicals, minerals, land flows, etc. to facilitate differential analysis. Twelve
      criteria were defined to evaluate flows against principles of clarity,
      consistency, extensibility, translatability, and uniqueness. Results and
      discussion: Over 134,000 elementary flows from five LCI databases, three LCIA
      methods, and four LCA software tools were collected and evaluated from European,
      North American, and Asian Pacific LCA sources. The vast majority were typed as
      "Element or Compound" or "Group of Chemicals" with less than 10% coming from the
      other seven types Many lack important identifying information including context
      information (environmental compartments), directionality (LCIA methods generally
      do not provide this information), additional clarifiers such as CAS numbers and
      synonyms, unique identifiers (like UUIDs), and supporting metadata. Extensibility
      of flows is poor because patterns in flow naming are generally complex and
      inconsistent because user defined nomenclature is used. Conclusions: The current
      shortcomings in flow clarity, consistency, and extensibility are likely to make
      it more challenging for users to properly select and use elementary flows when
      creating LCA data and make translation/conversion between different reference
      lists challenging and loss of information will likely occur. Recommendations: We
      recommend the application of a typology to flow lists, use of unique identifiers
      and inclusion of clarifiers based on external references, setting an exclusive or
      inclusive nomenclature for flow context information that includes directionality
      and environmental compartment information, separating flowable names from context
      and unit information, linking inclusive taxonomies to create limited patterns for
      flowable names, and using an encoding schema that will prevent technical
      translation errors.

PMID- 29456294
TI  - Cobalt-containing bioactive glasses reduce human mesenchymal stem cell
      chondrogenic differentiation despite HIF-1alpha stabilisation.
AB  - Bioactive glasses (BGs) are excellent delivery systems for the sustained release
      of therapeutic ions and have been extensively studied in the context of bone
      tissue engineering. More recently, due to their osteogenic properties and
      expanding application to soft tissue repair, BGs have been proposed as promising
      materials for use at the osteochondral interface. Since hypoxia plays a critical
      role during cartilage formation, we sought to investigate the influence of BGs
      releasing the hypoxia-mimicking agent cobalt (CoBGs) on human mesenchymal stem
      cell (hMSC) chondrogenesis, as a novel approach that may guide future
      osteochondral scaffold design. The CoBG dissolution products significantly
      increased the level of hypoxia-inducible factor-1 alpha in hMSCs in a cobalt dose
      dependent manner. Continued exposure to the cobalt-containing BG extracts
      significantly reduced hMSC proliferation and metabolic activity, as well as
      chondrogenic differentiation. Overall, this study demonstrates that prolonged
      exposure to cobalt warrants careful consideration for cartilage repair
      applications.

PMID- 29456296
TI  - Back to basics....

PMID- 29456297
TI  - Double pronged strategy with incremental efforts in generating awareness on oral
      hygiene day.

PMID- 29456295
TI  - User-Centered Design for Psychosocial Intervention Development and
      Implementation.
AB  - The current paper articulates how common difficulties encountered when attempting
      to implement or scale-up evidence-based treatments are exacerbated by fundamental
      design problems, which may be addressed by a set of principles and methods drawn
      from the contemporary field of user-centered design. User-centered design is an
      approach to product development that grounds the process in information collected
      about the individuals and settings where products will ultimately be used. To
      demonstrate the utility of this perspective, we present four design concepts and
      methods: (a) clear identification of end users and their needs, (b)
      prototyping/rapid iteration, (c) simplifying existing intervention
      parameters/procedures, and (d) exploiting natural constraints. We conclude with a
      brief design-focused research agenda for the developers and implementers of
      evidence-based treatments.

PMID- 29456298
TI  - Reactive lesions of oral cavity: A retrospective study of 659 cases.
AB  - Objective: This study reviews, analyzes, and compares the demographic data,
      histopathological features and discusses the treatment and prognosis of reactive
      lesions (RLs). Materials and Methods: Retrospective study was performed on the
      departmental archives from July 2006 to July 2016 (total 5000 cases) comprising
      of 659 cases of RLs of the oral cavity. The recorded data included age, gender,
      size, site, duration, habits, etiology, histopathological diagnosis, treatment,
      and prognosis. Results: The most common lesion was found to be inflammatory
      fibrous hyperplasia (47%) followed by pyogenic granuloma (PG) (27.16%) and the
      least cases were of peripheral giant cell granuloma (1.6%). The mean age for the
      occurrence was 4th-5th decade in all the RL's exceptperipheral ossifying fibroma
      (POF) which presented in the third decade. Female predominance was noted in all
      lesions except irritational FIB. The sizes of majority of the lesions were
      approximately 0.5-1 cm. The common sites were anterior maxilla followed by
      posterior mandible and least in tongue with no associated habits (82.2%). The
      duration of all the lesions was seen to be <1 year. Majority of them presented
      with poor oral hygiene status (87.2%). Recurrences were present in 13.5% of
      surgically excised lesions. Conclusion: The RLs present commonly in oral cavity
      secondary to injury and local factors which can mimic benign to rarely malignant
      lesions. The clinical and histopathological examination helps to categorize the
      type of lesions. The complete removal of local irritants with follow-up and
      maintenance of oral hygiene helps to prevent the recurrences of such lesions.

PMID- 29456299
TI  - Atomic Force Microscopy: A three-dimensional reconstructive tool of oral
      microbiota in gingivitis and periodontitis.
AB  - Aim: This study aims to ascertain the advantages of Atomic Force Microscopy (AFM)
      in the morphologic study of microorganisms and their interactions within the
      subgingival biofilm in patients with gingivitis and periodontitis. Settings and
      Design: Conducted a study on twenty patients, ten patients with severe
      periodontitis with probing the pocket depth of >=8 mm, with a clinical attachment
      loss (CAL) of >=6 mm CAL and ten patients with gingivitis: >=5 mm pocket depth,
      and no attachment loss, was selected for the study. Materials and Methods:
      Bacterial biofilms were collected and slide preparation done. Morphological study
      was done using AFM. AFM consists of a cantilever-mounted tip, a piezoelectric
      scanner, a photodetector diode, a laser diode, and a feedback control. The laser
      beam is reflected from back of the cantilever into the quadrant of the
      photodetector. AFM works on the principle of interaction between the tip and the
      sample which causes the cantilever to deflect, thereby changing the position of
      laser onto the photodetector. Methodology used for studying the bacteria through
      AFM includes the following: (1) Probe type: Platinum coated silicon nitrate tip.
      (2) Probe force: 0.11 N/m. (3) Probe geometry: Triangular shaped tip. (4) Probe
      frequency: 22 KHz. (5) Probe immobilization: Used in Contact mode. AFM Solver Pro
      M (NT-MDT) equipped with ETALON probe was used to take images in Nova software.
      Results: The investigation showed various morphological features, such as shape,
      size, and secretory product-like vesicles of the bacterial species involved in
      gingivitis and periodontitis. More bacterial surface details were studied by
      reproducing a three-dimensional reconstruction using AFM. Conclusions: The
      morphological variations of bacteria of different sizes, and shapes, cell wall
      structures, secretory product-like vesicles flagellated and filamentous
      microorganisms, polymorphonuclear leukocytes, and bacterial coaggregation
      analysis were done by AFM. Results of the present study conclude that AFM is a
      quite a reliable method for studying morphology of bacterial species involving
      periodontal diseases and is also used to study microbial interactions in biofilm.

PMID- 29456300
TI  - Comparative evaluation of the efficacy of a herbal mouthwash and chlorhexidine
      mouthwash on select periodontal pathogens: An in vitro and ex vivo study.
AB  - Background: Several herbal mouthwash and herbal extracts have been tested in
      vitro and in vivo in search of a suitable adjunct to mechanical therapy for long
      term use. In this study, we aimed to look at the antimicrobial effect of the
      herbal mouthwash and chlorhexidine (CHX) mouthwash on select organisms in in
      vitro test and an ex vivo model. Materials and Methods: The antimicrobial effects
      were determined against standard strains of bacteria that are involved in
      different stages of periodontal diseases. The in vitro tests included
      determination of minimum inhibitory concentration (MIC) using broth dilution and
      agar diffusion. In the ex vivo part of the study supragingival dental plaque were
      obtained from 20 periodontally healthy adult volunteers. Descriptive analysis was
      done for the entire quantitative and qualitative variable recorded. Results: The
      MIC by broth dilution method found no statistically significant difference
      between the mouthwashes. The agar dilution method showed CHX was more effective
      as compared to the herbal mouthwash against standard strains of Streptococcus
      mutans, Streptococcus sanguinis, and Aggregatibacter actinomycetemcomitans.
      However, no difference was observed between the mouthwashes for Porphyromonas,
      Pseudomonas aeruginosa, and Fusobacterium nucleatum. The ex vivo results conclude
      that none of the selected mouthwashes were statistically significantly different
      from each other. Conclusion: In the present study, CHX showed higher levels of
      antimicrobial action than the herbal mouthwash against bacterial species. The
      results reinforce the earlier findings that the in vitro testing is sensitive to
      methods and due diligence is needed when extrapolating the data for further use.
      However, long-term use and in vivo effectiveness against the periopathogens need
      to be tested in well-planned clinical trials.

PMID- 29456301
TI  - Correlative analysis of plasma and urine neopterin levels in the pre- and post
      menopausal women with periodontitis, following nonsurgical periodontal therapy.
AB  - Context: Periodontitis is an inflammatory condition which is distinguished by the
      devastation of the supported tooth structures. In such inflammatory conditions,
      some biomarkers such as neopterin will be secreted and elevated in the body
      fluids, which can be used as a diagnostic marker for the present and future
      disease activity. Aims: Assessment of the neopterin as a biomarker in
      inflammatory conditions such as menopause and periodontitis. Settings and Design:
      A cross-sectional interventional study. Materials and Methods: Sixty female
      individuals with a mean age of 40-60 years with chronic periodontitis were
      included in this study. All were categorized into two groups of thirty each,
      depending on their menstrual history: Group I - thirty premenopausal women and
      Group II - thirty postmenopausal women. Urine and plasma were collected from both
      groups to estimate neopterin levels. ELISA kit was used to assess the neopterin
      levels at baseline and after 3 months of nonsurgical periodontal therapy (NSPT).
      Statistical Analysis Used: IBM SPSS version 21 software. Results: A significant
      depreciation in the mean values of all the parameters from baseline to 3 months
      (P < 0.001), in the intragroup analysis, was observed. Plasma (0.006) and urine
      (0.004) reduction was seen. Conclusions: In both the groups, in 3 months after
      NSPT, decreased neopterin levels were found, suggesting that the NSPT is the
      definitive therapy. Further, suggesting that, neopterin levels in the plasma and
      urine can be used as an index to identify the periodontal inflammation and
      destruction.

PMID- 29456302
TI  - Impact of mandibular third molar extraction in the second molar periodontal
      status: A prospective study.
AB  - Aim: The aim of the present study was to assess the periodontal condition and
      sensitivity of second mandibular molars after the extraction of the adjacent
      third molar, while also assessing the quality of life of the patients. Materials
      and Methods: Twenty-three healthy patients were assessed in terms of probing
      depth, gingival height, gingival thickness, dental sensitivity, plaque index and
      bleeding on probing (adjacent second mandibular molar), before the surgical
      procedure, as well as 60 and 180 days after the surgery. The following data were
      also recorded and measured: the position and size of the impacted teeth; the size
      of the alveoli after surgery and the quality of life of the patient. Results:
      Significant differences were found for probing depth and gingival height before
      and after 180 days. The plaque index increased significantly after surgery (P =
      0.004), as did bleeding on probing. No significant difference was found for the
      quality of life. The size of the third molar extracted was correlated with
      bleeding on probing 180 days after the surgery. Conclusion: An improvement was
      noted in the periodontal condition of the second mandibular molars after the
      extraction, based on the assessments of probing depth and gingival height. The
      position of the third molar affected the periodontal condition of the second
      mandibular molar. No alterations were recorded for dental sensitivity or the
      quality of life after the extraction.

PMID- 29456303
TI  - Impact of nonsurgical periodontal therapy on total antioxidant capacity in
      chronic periodontitis patients.
AB  - Aim: The aim of this study was to determine the utility of plasma total
      antioxidant capacity (TAC) as marker of periodontal disease by estimating TAC of
      periodontally healthy and chronic periodontitis patients and the impact of
      scaling and root planning on total antioxidant status of periodontitis patients.
      Materials and Methods: Blood plasma samples were collected from randomly selected
      eighty individuals (40 periodontally healthy controls and 40 chronic
      periodontitis patients), with an age range of 20-45 years and were analyzed for
      TAC by ferric reducing antioxidant power assay. Scaling and root planing was
      performed in periodontitis patients, and TAC level was measured again after 3
      weeks. Data were analyzed with t-test, using SPSS software (PSAW, Windows version
      18.0). Results: The mean plasma TAC was significantly lower (792.33 +/- 124.33
      MUmol/L, P < 0.001) in chronic periodontitis patients compared to healthy control
      (1076.08 +/- 193.82 MUmol/L). Plasma TAC level increased significantly (989.75 +/
      96.80, P < 0.001) after scaling and root planing. Conclusions: An inverse
      relationship exists between plasma TAC and severity of chronic periodontitis
      suggesting disturbed oxidant-antioxidant balance in chronic periodontitis.
      Scaling and root planing resulted in the restoration of TAC to normal levels.
      These results are important from the perspective of including antioxidants in
      periodontal therapy regime to boost up body's antioxidant defense system and to
      reduce oxidative stress-mediated periodontal tissue damage. We concluded that TAC
      can be used as a biomarker to evaluate the health of periodontium.

PMID- 29456304
TI  - Effect of supragingival oral irrigation as an adjunct to toothbrushing on plaque
      accumulation in chronic generalized gingivitis patients.
AB  - Aim: The aim of this study was to evaluate the efficacy of supragingival oral
      irrigation either with water or different concentrations of chlorhexidine (CHX)
      digluconate as an adjunct to toothbrushing on plaque accumulation in chronic
      generalized gingivitis patients. Materials and Methods: Fifty patients were
      randomly allocated into five groups. Group 1: toothbrushing alone, Group 2:
      toothbrushing with mouthwash, Group 3: toothbrushing with water irrigation, Group
      4: toothbrushing with 0.0075% CHX digluconate (36 mg) supragingival irrigation,
      and Group 5: toothbrushing with 0.02% CHX digluconate (96 mg) supragingival
      irrigation. The collected data were subjected to statistical analysis.
      Statistical Analysis: Descriptive data were obtained for all outcome variables
      and reported as mean +/- standard deviation. The Student's t-test, Chi-square
      test, and one-way analysis of variance (ANOVA) were applied for the statistical
      evaluation of means and comparisons of proportions, and post hoc Bonferroni test
      was used for multiple comparisons after the application of the ANOVA test for
      comparison within the groups. Results: When intergroup difference of the mean
      differences was compared for individuals using toothbrushing along with 0.0075%
      CHX digluconate irrigation and those using toothbrushing along with 0.02% CHX
      digluconate irrigation from BL-14, BL-28, and between 14 and 28 days, it was
      found to be statistically nonsignificant. Conclusions: In our study, the CHX
      digluconate concentration for mouthwash and oral irrigation in addition with
      toothbrushing was found to be same, i.e., <50 mg for improving the gingival
      health by reducing gingival inflammation.

PMID- 29456305
TI  - A clinicoradiographic assessment of 1% metformin gel with platelet-rich fibrin in
      the treatment of mandibular grade II furcation defects.
AB  - Background: Management of furcation defects is challenging, and constantly newer
      therapeutic strategies are evolving. Platelet-rich fibrin (PRF) is successfully
      used alone and in combination with various agents in the furcation defects.
      Lately, metformin (MF), a second generation biguanide has gained popularity owing
      to its osteogenic potential. Aims and Objectives: The aim of the present study
      was to evaluate the clinical and radiographic effectiveness of open flap
      debridement (OFD) and PRF when compared to OFD + PRF + 1% MF gel in the
      management of mandibular Grade II furcation defects. Materials and Methods:
      Thirty mandibular grade II furcation defects were stratified into two groups; in
      one group OFD and PRF is used, and the other group had an additional MF gel with
      PRF in OFD. Clinical parameters such as plaque index, modified sulcus bleeding
      index, probing pocket depth (PD), relative vertical attachment level (RVAL), and
      relative horizontal attachment level (RHAL) were recorded at baseline and at 6
      months. Radiovisiography and ImageJ software were used to evaluate the intrabony
      defect depth. Results: The OFD + PRF + MF group showed significantly higher
      probing PD reduction, RVAL and RHAL gain than the OFD + PRF group. Conclusions:
      PRF when combined with a potential osteogenic agent like MF can provide a better
      therapeutic benefit to a furcation involved tooth.

PMID- 29456306
TI  - Chronic periodontitis among diabetics and nondiabetics aged 35-65 years, in a
      rural block in Vellore, Tamil Nadu: A cross-sectional study.
AB  - Background: Chronic periodontitis is a common cause of poor oral health globally.
      Those at higher risk of this preventable and easily treatable condition need to
      be identified so that efforts can be taken to decrease disease burden and
      subsequent consequences. Aims: The aims of the study were (1) To compare the
      prevalence of chronic periodontitis among individuals with and without type 2
      diabetes, aged 35-65 years from a rural block in Vellore, Tamil Nadu and (2) to
      assess risk factors for chronic periodontitis among individuals with diabetes.
      Settings and Design: A cross-sectional study was done in nine villages of
      Kaniyambadi block, Vellore, between October 2015 and July 2016 among participants
      aged 35-65 years of a previous cross-sectional survey which had identified
      individuals with and without type 2 diabetes. Materials and Methods: Chronic
      periodontitis was assessed using the Community Periodontal Index and Treatment
      Needs index. Oral hygiene was assessed clinically using the Simplified Oral
      Hygiene Index. Diabetes was defined as on medication for type 2 diabetes or
      detected to have fasting blood glucose >=126 mg/dl (in a previous survey).
      Statistical Analysis: Chi-square test and odds ratios (adjusted using logistic
      regression) were used to study risk factors for periodontitis among those with
      diabetes. Results: Prevalence of chronic periodontitis was 45.9% (95% confidence
      interval [CI]: 40.88%-50.9%) among 98 individuals with diabetes and 35.6% (95%
      CI: 30.91-40.29%) among 104 individuals without diabetes. Poor oral hygiene (odds
      ratio: 8.33, 95% CI: 3.33-25.00), low socioeconomic status (odds ratio: 3.19, 95%
      CI: 1.00-10.12), and smoking (odds ratio: 3.51, 95% CI: 1.17-10.51) were
      associated with periodontitis among diabetics. Conclusions: Individuals with type
      2 diabetes have a higher prevalence of periodontitis. As poor oral hygiene is a
      strong risk factor for periodontitis, there is a need for targeted education
      regarding dental hygiene to reduce this preventable condition.

PMID- 29456307
TI  - Awareness, knowledge, and attitude of patients toward dental implants - A
      questionnaire-based prospective study.
AB  - Background: In developing nations like India awareness and education about dental
      implants as a treatment modality is still scanty. Aim: The study was conducted to
      determine the awareness, knowledge, and attitude of patients toward dental
      implants as a treatment modality among the general population and to assess the
      influence of personality characteristics on accepting dental implants as a
      treatment modality in general and as well as treatment group. Materials and
      Methods: A structured questionnaire-based survey was conducted on 500 randomly
      selected participants attending the outpatient department. The study was
      conducted in 2 parts. In the first part of the study, level of awareness,
      knowledge, and attitude was assessed. In the second part of the study,
      interactive educational sessions using audiovisual aids were conducted following
      which a retest was conducted. The participants who agreed to undergo implant
      treatment were followed up to assess their change in attitude towards dental
      implants posttreatment. Thus pain, anxiety, functional, and esthetic benefits
      were measured using visual analog scale. They were further followed up for 1 year
      to reassess awareness, knowledge, and attitude towards dental implants. Results:
      A total of 450 individuals completed the questionnaires. Only 106 individuals
      agreed to participate in the educational sessions and 83 individuals took the
      retest. Out of these, only 39 individuals chose implants as a treatment option. A
      significant improvement in the level of information, subjective and objective
      need for information, was noted after 1 year. Conclusion: In this study, a severe
      deficit in level of information, subjective and objective need for information
      towards, dental implants as a treatment modality was noted. In the treatment
      group, a significant improvement in perception of dental implant as a treatment
      modality suggests that professionally imparted knowledge can bring about a change
      in the attitude.

PMID- 29456308
TI  - Gingival enlargement unveiling Crohn's disease - A report of a rarefied case.
AB  - This article highlights a peculiar case of Crohn's disease (CD) with the primary
      presenting symptom as localized gingival overgrowth in the anterior region of
      maxilla. The patient underwent surgical treatment with external bevel
      gingivectomy procedure. Follow-up after 6 months revealed no recurrence. A final
      diagnosis of CD was made, after following histopathological evaluation of the
      gingival biopsy and other special investigations. It is thus crucial to associate
      the localized granulomatous gingival overgrowth to systemic signs of CD.
      Intraoral occurrence preceding intestinal involvement is very rare in CD with an
      incidence of about 8%-9% of patients. Therefore, precise diagnosis, treatment
      planning, and timely management are vital to the overall health and welfare of
      patients.

PMID- 29456309
TI  - Idiopathic peripheral ossifying fibroma in a young adolescent girl: A very rare
      clinical presentation.
AB  - The use of the term "fibroma" for any soft-tissue lesion or gingival lesion by
      general practitioners has led to inadequate diagnosis of quite a few rare
      entities. The occurrence of gingival lesions in adolescent female patients is a
      routine clinical finding. The site of occurrence of such a lesion is of prime
      significance, as the rarity of these lesions is determined by the site and size
      of the lesion. On the other hand, the dilemma over the diagnosis of peripheral
      ossifying fibroma (POF) versus peripheral odontogenic fibroma still continues.
      Commonly used synonyms for POF include calcifying fibroblastic granuloma,
      peripheral fibroma with calcification, peripheral cementifying fibroma, and
      calcifying or ossifying fibrous epulis. The present case report deals with the
      management of a unique case of POF between two maxillary central incisors in an
      adolescent female child patient, followed up to 2-year postsurgical excision.

PMID- 29456310
TI  - Applications of a modified palatal roll flap in peri-implant soft-tissue
      augmentation - A case series.
AB  - Abrams's palatal roll technique has been used extensively to augment peri-implant
      soft tissues in the maxillary esthetic zone and has seen numerous modifications.
      An adaptation of the palatal roll technique is described here and its simplicity
      of application in three different scenarios is demonstrated. At second-stage
      implant surgery, a partial thickness initial incision followed by a palatal
      subepithelial dissection at the site of implant was done and a connective tissue
      graft with a buccal pedicle was obtained. The graft was rolled under the buccal
      flap and allowed to heal with the support of a healing abutment. The graft healed
      uneventfully and provided excellent contours of tissues around the implant. The
      procedure demonstrated good results for augmentation of a buccal ridge
      deficiency, for covering exposed and unsightly implant fixtures and was also done
      with a papilla preservation incision. In addition, a second surgical site to
      obtain the connective tissue graft was avoided.

PMID- 29456311
TI  - Management of fenestration using bone allograft in conjunction with platelet-rich
      fibrin.
AB  - Fenestration and dehiscence are said to be anatomical variations of cortical bone
      and not true pathological entities. They represent window-like defects covered by
      periosteum and overlying gingiva with or without the intact marginal bone. The
      etiology of such defects is still unclear, though many hypotheses such as
      occlusal traumatism, trauma, and variation in root bone angulation have been put
      forward. Diagnosis of such defects is challenging clinically, and they cannot be
      appreciated in conventional radiographs. In many instances, they are accidentally
      discovered during periodontal and oral surgical procedures. These defects, if not
      treated, can affect prognosis and complicate healing of the affected teeth.
      Treatment of such cortical bony defects is challenging and involves the use of
      potential regenerative materials to aid in regeneration. This case report
      describes the successful management of such a defect, discovered through
      exploratory flap approach, using PRF in conjunction with bone allograft.

PMID- 29456312
TI  - Long-term effect of Lactobacillus brevis CD2 (Inersan(r)) and/or doxycycline in
      aggressive periodontitis.
AB  - Context: The over usage and broad use of antibiotics resulted in the emergence of
      resistant microorganisms to the drugs which also disturb the indigenous
      microflora, which include the Lactobacillus in the oral cavity. Hence, it is
      preferred to avoid the use of antibiotics. Aims: The hypothesis tested in this
      study was that 14 days of treatment with Lactobacillus brevis CD2 lozenges, L.
      brevis CD2 with oral doxycycline, or doxycycline alone would have a beneficial
      effect on periodontal health after 5 months. Settings and Design: It was a
      randomized clinical trial. Materials and Methods: Eighteen nonsmoking patients
      aged 14-35 years, with aggressive periodontitis, were randomized to receive 14
      days of treatment with L. brevis CD2 lozenges (two lozenges daily), L. brevis CD2
      lozenges with oral doxycycline (100 mg tablet once daily), or doxycycline alone.
      Saliva samples were taken on day 0, 2 weeks, 2 months, and 5 months. Clinical
      parameters (plaque index, gingival index, probing pocket depth, and clinical
      attachment level) and microbiological parameters (lactobacilli and
      Aggregatibacter actinomycetemcomitans) were evaluated. Statistical Analysis Used:
      Changes between groups were evaluated using repeated measure analysis of
      variance. Results: All clinical parameters shown to be numerically improved at 5
      months when compared with baseline in all the three groups. The improvement (P <
      0.01) in gingival index was statistically significant, and the intergroup results
      were also statistically significant (P < 0.01). Conclusions: Fourteen days of
      treatment with lozenges having L. brevis CD2 have a lasting effect on clinical
      measures of aggressive periodontitis, particularly gingival index. This effect
      appears to be equivalent to that produced by doxycycline.

PMID- 29456313
TI  - Child sexual abuse: the suffering untold.

PMID- 29456315
TI  - Stressful life events and severity of alcohol consumption in male psychiatric
      inpatients.
AB  - Aim: To assess the levels of alcohol consumption and the level of stress faced by
      male patients hospitalized with psychiatric disorders in a military hospital.
      Materials and Methods: This cross-sectional study was conducted on 100
      consecutive patients admitted to a tertiary care psychiatric center and 100
      controls. The patients with psychiatric ailments were first stabilized mentally
      and physically and then assessed. For the collection of demographic data, a
      questionnaire was prepared which was administered to all patients. The Armed
      Forces Medical College Life Events scale was used for the assessment of stressful
      life events. The Michigan Alcohol Screening Test (MAST) was applied as a
      screening procedure for alcohol use disorder. For assessing the severity of
      alcohol consumption, the Hilton Drinking Behavior Questionnaire (HDBQ) was
      utilized. Results: Analysis revealed that 16% of the psychiatric patients scored
      above the cutoff score on the MAST compared to 2% of controls. On the HDBQ, 22%
      of the psychiatric patients had a significant score compared to 4% of controls.
      Patients with psychiatric disorders experienced significantly more number of life
      events compared to the controls irrespective of the length of service. The
      Psychiatric group experienced significantly more life change units both in 1-year
      prior and in lifetime period. Conclusion: Psychiatric patients face significantly
      higher stressful life events, experience significantly more life changes, and
      consume significantly more alcohol as compared to healthy participants.

PMID- 29456314
TI  - Child sexual abuse and the development of psychiatric disorders: a
      neurobiological trajectory of pathogenesis.
AB  - Child sexual abuse (CSA) is an important public health problem with long-standing
      neurobiological, developmental, and psychiatric abnormalities. The present review
      analyzes the long-term effects of CSA from a developmental, psychiatric
      morbidity, neurochemical and neurobiological perspective and then tries to posit
      a developmental neurobiological trajectory from CSA to the genesis of
      psychopathology in later life. The role of various neurotransmitters such as
      serotonin and dopamine affected by CSA are discussed. Serotonin abnormalities
      have been reported in various studies among participants exposed to CSA.
      Structures such as the prefrontal cortex, superior temporal gyrus, corpus
      callosum, parietal lobes, hippocampus, and cerebellum all demonstrate volumetric
      and structural changes in response to the trauma of CSA. Neurocognitive studies
      demonstrate memory and spatial awareness as well as decrements in general
      cognitive performance and memory when compared to normal individuals. The
      hypothalamic-pituitary-adrenal axis has also been implicated in CSA, and there is
      an alteration in corticotropin-releasing hormone response due to the continuous
      cumulative trauma of CSA. This paper also reviews a section on the role of
      genetic and epigenetic factors in the development of psychiatric disorders as a
      result of exposure to episodes of CSA where studies have demonstrated changes in
      DNA methylation in response to CSA. This review tries to hypothesize a
      developmental trajectory framework which is individual for every case where
      exposure to CSA may lead to psychopathology and psychiatric morbidity later in
      life. Rapid and emerging fields such as developmental traumatology in relation to
      CSA are also discussed.

PMID- 29456316
TI  - Prevalence and patterns of tobacco use and nicotine dependence among males
      industrial workers.
AB  - Background: Tobacco use is an important preventable health risk factor in India.
      Aim: This study was carried out to estimate the prevalence of current tobacco
      use, factors and extent of dependence associated with its use among male workers
      of an industrial organization. Materials and Methods: A total of 759 participants
      randomly selected from the population of employees were administered
      questionnaire in Hindi containing demographic profile, patterns of smoking, and
      use of smokeless tobacco and alcohol. Results: Forty-one percent of the surveyed
      males (n = 750) used tobacco either by smoking or smokeless method or both (9.7%
      used both, 23.4% smoked, and 27.3% used smokeless tobacco). The maximum
      percentage was among the 26-30 years' age group, and the married persons (45.4%,
      OR = 2.17, P < 0.05). Tobacco use was associated with lower educational
      qualifications, history of tobacco use in family members, and drinking alcohol.
      Seventy-two percent of the nicotine users reported being influenced by their
      peers in initiating the habit, 59.4% of the users reported being advised to stop
      tobacco use by a health professional, and 52.9% had attempted quitting the habit
      more than once. Twenty percent of our sample were dependent on nicotine and the
      highest prevalence was seen in those using both smoking and the smokeless
      tobacco. Conclusions: The Prevalence of Tobacco Use and Nicotine Dependence among
      male industrial employees is significant and necessitates Tobacco awareness and
      cessation programs regarding Tobacco use.

PMID- 29456317
TI  - Clinico-psycho-social profile of patients brought under consultation-liaison
      psychiatry care in a large tertiary care referral hospital.
AB  - Objective: The aim of this study was to access the clinico-psycho-social profile
      of patients brought under consultation-liaison (CL) psychiatry care in a large
      tertiary care referral hospital. Materials and Methods: This study included all
      patients who were referred for CL psychiatry from among the inpatients in the
      hospital and the emergency department (during off working hours of the hospital)
      over a period of 1 year. Data were obtained and analyzed in terms of where was
      the referral placed, by whom, the reason for placing the referral, the primary
      medical/surgical diagnosis of the patient, the presenting complaints, any past
      psychiatric history, the psychiatric diagnosis (as per the International
      Classification of Diseases, Tenth Edition), the investigations advised and their
      reports, the treatment advised (psychotherapeutic and psychopharmacological), the
      sociodemographic profile of the patients, and the follow-up details. Results: A
      total of 157 patients were referred to the CL unit over the study period. Out of
      these, 125 patients were referred among the inpatients and 32 from the emergency
      department of the hospital. Majority of the patients were in the age group of 25
      50 years and were male. The majority of the referrals were made by general
      physician; most of the referrals were placed from emergency department. The most
      common reason for referral was for altered sensorium and behavioral
      abnormalities. The most common diagnosis was delirium followed by depressive
      episode and alcohol dependence syndrome. Conclusion: There was higher
      representation of delirium and alcohol-related cases in our study compared to
      older studies.

PMID- 29456318
TI  - Characteristics of suicidal attempts among farmers in rural South India.
AB  - Background: Globally, farming as an industry is considered a high-risk occupation
      for suicides. Certain states in India like Karnataka have a suicide rate higher
      than the national average, and this is generally attributed to the farmers'
      suicide. Aims: The aim is to study the characteristics of suicidal attempts among
      the farmer community in South India, with special emphasis on gender differences,
      modes used, and the immediate precipitant causes. Materials and Methods:
      Retrospective, case register-based, explorative-descriptive study of 426
      consecutive medicolegal case files of patients whose stated occupation was
      farming and who were admitted as cases of deliberate self-harm or suicide attempt
      to a rural tertiary care hospital in rural South India. Results: Out of the 426
      farmers who attempted suicide, majority were male (355, 83.3%), in the age group
      of 21-40 years (318, 75%), married (358, 84%), and belonging to lower
      socioeconomic status (268, 62.9%). About 54% of them had attempted suicide by
      consuming pesticides (230). Surprisingly, 183 (43%) and 86 (20.2%) reported the
      immediate precipitant as being relationship issues and marital conflict,
      respectively, and only 100 (23.5%) attributed it to financial reasons. Females
      were significantly associated with a past history of suicidal attempt while males
      tended to abuse alcohol before an attempt more frequently. Conclusions: Pesticide
      poisoning was the most common mode for attempting suicide among the farmers.
      Contrary to public perception and other studies, relationship, and marital
      issues, not financial reasons were found to be the most common immediate
      precipitant for the attempters in our study.

PMID- 29456319
TI  - Lifetime alcohol consumption and severity in alcohol dependence syndrome.
AB  - Introduction: Alcohol dependence syndrome is a major public health issue globally
      and is responsible for significant morbidity and mortality. The total dose of
      alcohol consumed has been linked to liver diseases, pancreatitis, and other
      alcohol-related medical consequences. However, this has not been studied in
      relation to severity of dependence; although it is well known that alcohol causes
      neuronal damage, which in turn potentiates dependence. Thus, there is a need to
      study the relationship between the amount of alcohol consumed and severity of
      dependence. Materials and Methods: A total of 165 consecutive cases of alcohol
      dependence syndrome were studied in a General Hospital Psychiatry Unit at a
      tertiary care hospital. Addiction Severity Index (ASI) was used to evaluate the
      severity of alcohol dependence, and Life Time Alcohol Consumption (LTAC) was
      evaluated by taking careful history. Correlation coefficients were calculated
      between ASI and LTAC. Group differences were analyzed using t-test. Results:
      There was a significant correlation between ASI and LTAC (r = 0.162, P = 0.032),
      which was highly significant in the subgroup without medical complications (r =
      0.250, P = 0.003). A similar correlation in the medical complications subgroup
      was not significant. Conclusions: Lifetime alcohol consumption co-related with
      the severity of alcohol dependence, particularly in those presenting without
      medical complications (i.e., those with behavioral and social consequences, and
      injuries).

PMID- 29456320
TI  - Failure to utilize feedback during explicit decision-making task in alcohol
      dependent patients.
AB  - Background: Patients who are diagnosed with alcohol-dependent syndrome (ADS) are
      shown to have neuropsychological deficits, especially executive function (EF)
      deficits. Among the EFs, decision-making is one such function which has
      consistently been shown to be impaired in people who are dependent on alcohol,
      compared to controls. Decision-making in this population is usually assessed with
      gambling-type tasks. However, some of these tasks are ambiguous, work on chance
      factors, rarely match with real-life gambling situations, and/or involve
      nonconscious mechanisms. Materials and Methods: The current study compared 26
      male patients with ADS (P-ADS) with equal number of their nonalcohol-dependent
      male siblings on sensation seeking and explicit gambling task (EGT). EGT is
      similar to the Iowa gambling task in administration, but varies from it as it
      involves a single outcome and provides unambiguous, explicit, and continuous
      feedback for the participants. Results and Conclusion: The results did not show
      any significant relationship between decision-making variables and sensation
      seeking. However, despite unambiguous, explicit, and continuous feedback,
      patients showed significantly poor decision-making as compared to the siblings of
      the P-ADS group. This study throws light on why people who are addicted to
      alcohol have difficulties in decision-making, despite knowing the adverse
      effects.

PMID- 29456321
TI  - Study of personality traits, individual coping resources, and their association
      in HIV-seropositive males.
AB  - Background: HIV infection is an unfortunate consequence of a defined set of
      behaviors. Individuals with continued high-risk behavior either due to
      personality factors or due to maladaptive coping skills have higher viral loads
      and morbidity. Research has shown significant interactions between less effective
      coping styles and personality factors. Aim: This study aimed to evaluate
      personality traits, coping skills, and their association in male HIV-seropositive
      cases. Materials and Methods: This was a cross-sectional study, conducted on 86
      patients. Informed consent and sociodemographic details, by a structured
      questionnaire, were obtained. Scales pertaining to personality factors and coping
      were applied. Statistical analysis was done by SPSS 16. Results: Neuroticism,
      extraversion, and conscientiousness traits were in the average range. Scores on
      openness and agreeableness were below average. The results pertaining to coping
      showed an overall mean score of 50.78, with the highest on physical domain and
      then on the philosophical domain, the lowest was in social domain. The research
      sample perceived their coping resources as average. Neuroticism was negatively
      related to all the coping styles. Extraversion showed relation with physical,
      emotional, social, and philosophical scales. Openness was related to
      philosophical and emotional scales. Agreeableness correlated with all domains of
      coping except the social. Conscientiousness correlated significantly with all the
      domains of coping. Conclusion: The various personality traits associated with
      male HIV-seropositive patients were identified and various coping resources used
      by these were also delineated. Further, the association among them was identified
      which can help in primary prevention and mental health professionals to have a
      targeted approach for counseling.

PMID- 29456322
TI  - Images of psychiatry: Attitude survey of teaching medical specialists of India.
AB  - Context: Attitude of teaching medical specialists shapes those of future doctors.
      Region-specific data on teaching medical specialists' attitudes toward psychiatry
      (ATP) are lacking from India. Aims: This study aimed to assess the attitudes of
      teaching medical specialists toward psychiatry and its association with
      sociodemographic profile and career stage. Settings and Design: This is a cross
      sectional descriptive survey. Materials and Methods: Attitude towards psychiatry
      (ATP) was assessed from 188 specialists from All India Institute of Medical
      Sciences (AIIMS) Bhubaneswar and AIIMS Jodhpur using modified ATP scale-30.
      Statistical Analysis: Descriptive statistical analysis was done using SPSS
      version 16.0. Associations of ATP with sociodemographic status, career stage, and
      family history of psychiatric illness were done using logistic regression
      analysis. Results: Overall response rate was 81.68%, and gender (confidence
      interval [C.I.]: 2.026-7.410, P = 0.000) and super-specialization (C.I.: 2.167
      19.479, P = 0.021) were independent significant predictors for difference in
      attitudes. Female gender and super-specialization were associated with better
      attitudes. Ninety percent of participants had favorable attitude toward
      psychiatric illness. Four-fifth felt psychiatric patients to be as human as other
      patients and found psychiatric treatments effective. More than half felt that
      psychiatry does not stand among the three most exciting specialties and
      psychiatrists get less work satisfaction. Only one third said that they would
      have liked to be a psychiatrist. Conclusions: Attitudes were favorable toward
      patients and psychiatric interventions whereas unfavorable toward psychiatry as a
      discipline.

PMID- 29456323
TI  - Cross-sectional study of anxiety symptoms in students in preexamination period.
AB  - Background: Preexamination period is an exceptionally stressful time for
      schoolgoing children and adolescents, and the propensity of having anxiety
      symptoms increases. Aim: This study aimed to assess the presence of anxiety
      symptoms in students in preexamination period. Materials and Methods: The study
      was carried on 619 children from Class VIII to XI. All of them were given a
      structured questionnaire for sociodemographic profile and Screen for Child
      Anxiety Related Emotional Disorders questionnaire. Association of various
      variables with presence of anxiety symptoms was assessed. Statistics was analyzed
      with SPSS version 17.0 software. Results: Totally 170 children (27.5%) had
      anxiety symptoms, similarly the various subgroups had increased frequency
      compared to the known prevalence in this age group. Age, years spent in the
      current school, living with parents, presence of domestic stressors, and grade
      deterioration, all were significantly associated with increased frequency of
      these symptoms. Similarly, association with various subgroups is described.
      Conclusion: This study attempts to give evidence of increased anxiety symptoms,
      during preexamination phase, compared to the reported prevalence in this age
      group, and thus to address this becomes imperative which will improve their
      performance and also the mental health preventing distress along with
      psychological and behavioral problems.

PMID- 29456324
TI  - Stress and suicidal ideation among adolescents having academic difficulty.
AB  - Background and Objectives: Academically typically achieving adolescents were
      compared with students having academic difficulty on stress and suicidal ideas.
      Materials and Methods: In a cross-sectional study, 75 academically typically
      achieving adolescents were compared with 105 students with academic difficulty
      and 52 students with specific learning disability (SLD). Academic functioning was
      assessed using teacher's screening instrument, intelligence quotient, and
      National Institute of Mental Health and Neurosciences index for SLD. Stress and
      suicidal ideas were assessed using general health questionnaire, suicide risk-11,
      and Mooney Problem Checklist (MPC). Appropriate statistical methods were applied.
      Results: Three groups were comparable on age, gender, mother's working status,
      being only child, nuclear family, self-reported academic decline, and type of
      school. About half of adolescents reported psychological problems on General
      Health Questionnaire (mean score >3 in all the groups). Academically typically
      achieving adolescents showed higher stressors in peer relationships, planning for
      future and suicidal ideation compared to adolescents with academic difficulty.
      Adolescents face stress regarding worry about examinations, family not
      understanding what child has to do in school, unfair tests, too much work in some
      subjects, afraid of failure in school work, not spending enough time in studies,
      parental expectations, wanting to be more popular, worried about a family member,
      planning for the future, and fear of the future. Significant positive correlation
      was seen between General Health Questionnaire scores and all four subscales of
      MPC. Suicidal ideas showed a negative correlation with MPC. Interpretations and
      Conclusions: Adolescents experience considerable stress in multiple areas
      irrespective of their academic ability and performance. Hence, assessment and
      management of stress among adolescents must extend beyond academic difficulties.

PMID- 29456325
TI  - A study on different forms of intelligence in Indian school-going children.
AB  - Introduction: Most definitions of intelligence focus on capabilities that are
      relevant to scholastic performances. However, there are seven forms of
      intelligences. There is a lack of data on multiple intelligences in Indian
      children. Hence, this study was conducted to assess different forms of
      intelligences in students and compared these diverse intelligences with
      intelligence quotient (IQ) scores. Materials and Methods: In this cross-sectional
      observational study, we recruited 1065 school children between the age of 12 and
      16 years from two government and 13 private schools in five towns, six cities,
      and two villages across India. All the children were administered multiple
      intelligences questionnaire by Armstrong, consisting of thirty true/false types
      of questions to assess the intelligences of a child in seven domains including
      linguistic skills, logical/mathematical abilities, musical skills, spatial
      intelligence, bodily-kinesthetic skills, intrapersonal intelligence, and
      interpersonal intelligence. IQ scores were assessed by Ravens Standard
      Progressive Matrices. Results: We found that different students possessed
      different forms of intelligences and most students had more than one forms of
      intelligence. Of seven forms of intelligence, only three forms of intelligence
      such as logical/mathematical, musical, and spatial were positively correlated
      with the IQ score. Conclusions: Even in the children with low IQ, many students
      had other forms of intelligences. The IQ scores correlated with only
      logical/mathematical, spatial, and musical intelligence. Hence, tapping the
      intelligences of students can help enhance their learning process. Our curriculum
      should have an amalgamation of teaching for all kinds of intelligences for
      maximum productivity.

PMID- 29456326
TI  - Effect of type of schooling and gender on sociability and shyness among students.
AB  - Background: Sociability and shyness are orthogonal personality traits, wherein
      both are characterized by varying behavioral and psychophysiological correlates.
      Shyness should not be equated with the lack of sociability, as shyness relates to
      discomfort that occurs in the presence of others and sociability is identified
      with an individual's preference for being with others rather than alone.
      Objectives: The objective of this study was to examine the effect of type of
      schooling on sociability and shyness among students and to study the gender
      differences between sociability and shyness among students. Methodology: The
      sample comprised 210 students from both private and government schools situated
      in Delhi. Data were collected using Eysenck Personality Profiler for measuring
      sociability and Revised Cheek and Buss Shyness Scale. Results and Conclusion: The
      results obtained from ANOVA revealed that government school students were
      observed to be more sociable as compared to private school students. On the other
      hand, private school students were found to be more shy as compared to government
      school students. Females were observed to be more shy as compared to males. In
      addition, significant interactive effect was observed for sociability when school
      and gender were taken altogether.

PMID- 29456327
TI  - Study of insomnia in rotating shift-workers.
AB  - Background: Shift-workers commonly suffer from insomnia. This study evaluates
      different domains of insomnia. Aim: This study was aimed to study sleep and
      insomnia in rotating shift-workers and compare with day-workers. Materials and
      Methods: This was case-control study. The sleep of rotating shift-workers is
      compared with day workers using Athens Insomnia Scale. Results: Rotating shift
      workers had significantly higher scores on Athens insomnia scale on domains of
      initial, intermediate and terminal insomnia than day workers. Duration and
      quality of sleep and sense of well-being are lower in rotating shift-workers.
      Rotating shift-workers also experienced more day-time sleepiness than day
      workers. However, there was no difference in perceived physical and mental
      functioning between the two groups. Conclusion: Individuals working in rotating
      shifts for more than 15 days have significantly higher prevalence of insomnia
      than day-workers.

PMID- 29456328
TI  - Prevalence of depression and its relation to stress level among medical students
      in Puducherry, India.
AB  - Background: Currently, depression among medical students is an important health
      issue at the global level. There is also a paucity of information on its relation
      to the stress level. Objective: The aim of this study is to assess the prevalence
      of depression and its relation to stress level and other factors among medical
      students. Materials and Methods: A cross-sectional study was conducted among
      medical students at a tertiary care medical institution in Puducherry, coastal
      south India. Beck Depression Inventory Scale was used for screening of depression
      and Cohen's Perceived Stress scale to assess perceived stress level. Data on
      associated factors were collected by self-administered questionnaire. Results:
      The overall prevalence of depression was found to be 48.4% (215/444). According
      to the cutoff scores, 229 (51.6%) students scored as normal (0-9), 149 (33.6%) as
      mild (10-18), 60 (13.5%) as moderate (19-29), 3 (0.7%) as severe (30-40), and 3
      (0.7%) students scored as very severe (>40) depression. Depression was
      significantly less among those with mild stress (adjusted odds ratio [OR] =
      0.010) and moderate stress level (adjusted OR = 0.099) compared to severe stress
      level and those without interpersonal problems (adjusted OR = 0.448). Conclusion:
      Depression is more common among medical students. Stress coping mechanisms and
      improvement of interpersonal relationship may help to reduce depressive symptoms
      among medical students.

PMID- 29456329
TI  - A descriptive study of behavioral problems in schoolgoing children.
AB  - Background: Behavioral problems among schoolgoing children are of significant
      concern to teachers and parents. These are known to have both immediate and long
      term unfavorable consequences. Despite the high prevalence, studies on
      psychiatric morbidity among school children are lacking in our country. Materials
      and Methods: Five hundred children aged 6-18 years were randomly selected from a
      government school in Kanpur, Uttar Pradesh, and assessed for cognitive,
      emotional, or behavioral problems using standardized tools. Results: About 22.7%
      of children showed behavioral, cognitive, or emotional problems. Additional
      screening and evaluation tools pointed toward a higher prevalence of
      externalizing symptoms among boys than girls. Conclusion: The study highlights
      the importance of regular screening of school children for preventive as well as
      timely remedial measures.

PMID- 29456330
TI  - A study of individuals with intentional self-harm referred to psychiatry in a
      tertiary care center.
AB  - Background: Intentional self- harm (ISH) is one of the commonest yet neglected
      entities of Consultation liaison Psychiatry. More researches in the field of ISH
      are needed to effectively manage this problem. Aim: To study the socio
      demographic and clinical profile of subjects of ISH referred to Psychiatry in a
      tertiary care hospital. Materials and Methods: All subjects of ISH referred to
      department of Psychiatry, of a tertiary centre, on specified days were recruited
      in to the study after obtaining an informed consent. Socio-demographic details,
      details of psychiatric assessment were documented using a semi structured
      proforma. Appropriate management was done. Results: Forty one subjects were
      included in the study. About two third of them belonged to the age group of 18 to
      35 years. 56% of them were males, and 71% were married. House wives and students
      formed a significant proportion of sample. Most common method of ISH was self
      poisoning. About two third of the patients had no diagnosable psychiatric
      illness. Interpersonal conflicts with family members (47%), conflicts with spouse
      (22%), broken emotional relationship (18%) were common causes for impulsive acts
      of ISH. Conclusions: ISH is common amongst young, married males. About two third
      of those who attempt ISH have no diagnosable psychiatric illness, in rest,
      neurotic stress related disorders, personality disorders and substance use
      disorders were predominant.

PMID- 29456331
TI  - Valproate induced hyperammonemic encephalopathy treated by haemodialysis.
AB  - Valproate (VPA)-induced hyperammonemic encephalopathy is an unusual, but serious,
      adverse effect of divalproex sodium (DVPX) treatment and if untreated can lead to
      raised intracranial pressure, seizures, coma, and eventually death. It can,
      however, be reversed if an early diagnosis is made. It is therefore extremely
      important to recognize it and discontinue DVPX treatment. Our patient developed
      sudden deterioration of sensorium, drowsiness, lethargy, and later severe
      comatose state after few days of starting DVPX with high levels of serum ammonia
      despite therapeutic levels of VPA and normal liver function test. He responded to
      hemodialysis, cerebral decongestants, and other intensive supportive measures.

PMID- 29456332
TI  - Clozapine-induced hypertension: A case report and review of literature.
AB  - There are very few reports which suggest an association between clozapine and
      hypertension. We report a case in which a direct link of initiation of clozapine
      to development of hypertension which required pharmacological intervention. A 32
      year-old male who did not have any history of hypertension and had normal blood
      pressure at the baseline developed high blood pressure (i.e., 150/90 mmHg) while
      on clozapine 100 mg/day. Reduction of the dose of clozapine to 75 mg/day led to
      the return of blood pressure to baseline, with increase in blood pressure to
      150/90 mmHg on increasing the dose of clozapine again, requiring tablet atenolol
      50 mg/day for normalization of blood pressure with concomitant continuation of
      atenolol. Later, clozapine was increased to 350 mg/day, with no recurrence of
      raise in blood pressure. After 6 months, tablet atenolol was stopped with no
      evidence of hypertension in follow-up. To conclude, this case report suggests
      that clozapine can rarely lead to hypertension during the initial phase of
      treatment.

PMID- 29456333
TI  - Selfie use: The implications for psychopathology expression of body dysmorphic
      disorder.
AB  - Preoccupation with a body part can lead to indulgence in various forms of coping
      behavior. Users are frequently using technology as well as selfie to overcome
      their anxiety to relate to a body part as well as get approval from other online
      users. The present case highlights the excessive use of selfie to manage the
      distress-related body dysmorphic disorder (BDD). Psychiatric interview and
      assessment tools were used to elicit information about BDD, technology use, and
      affective states. Repeated use of selfie has been thought to manage the distress
      associated with appearance. It implies the need for screening excessive use of
      technology as comorbid condition and psychoeducation for promotion of healthy use
      of technology.

PMID- 29456334
TI  - Epilepsy, Behavioral Problems, and Intellectual Disability among Children in
      India: Conundrums and Challenges.

PMID- 29456335
TI  - Botulinum Toxin for Refractory Trigeminal Neuralgia: A Trial Sequential Analysis
      of Randomized Clinical Trials.

PMID- 29456336
TI  - Using of Fresh Cadaveric Cow Brain in the Microsurgical Training Model for Sulcal
      Cisternal and Fissural Dissection.

PMID- 29456337
TI  - Evaluation of Predictive Factors Influencing Community Reintegration in Adult
      Patients with Stroke.
AB  - Objectives: Patients with stroke are faced with gait, balance, and fall
      difficulties which could impact on their community reintegration. In Nigeria,
      community reintegration after stroke has been understudied. The objective of this
      study was to evaluate the predictors of community reintegration in adult patients
      with stroke. Materials and Methods: Participants were 91 adult patients with
      stroke. Gait variables, balance self-efficacy, community balance/mobility, and
      fall self-efficacy were assessed using Rivermead Mobility Index, Activities
      specific Balance Confidence Scale, Community Balance and Mobility Scale, and
      Falls Efficacy Scale-International respectively. Reintegration to Normal Living
      Index was used to assess satisfaction with community reintegration. Pearson
      Product-Moment Correlation Coefficient was used to determine the relationship
      between community reintegration and gait spatiotemporal variables, balance
      performance, and risk of fall. Multiple regression analysis was used to determine
      predictors of community reintegration (P <= 0.05). Results: There was significant
      positive relationship between community reintegration and cadence (r = 0.250, P =
      0.017), functional mobility (r = 0.503, P = 0.001), balance self-efficacy (r =
      0.608, P = 0.001), community balance/mobility (r = 0.586, P = 0.001), and
      duration of stroke (r = 0.220, P = 0.036). Stride time (r = -0.282, P = 0.073)
      and fall self-efficacy (r = 0.566, P = 0.001) were negatively correlated with
      community reintegration. Duration of stroke, balance self-efficacy, community
      balance/mobility, and fall self-efficacy (52.7% of the variance) were the
      significant predictors of community reintegration. Conclusion: Community
      reintegration is influenced by cadence, functional mobility, balance self
      efficacy, community balance/mobility, and duration of stroke. Hence, improving
      balance and mobility during rehabilitation is important in enhancing community
      reintegration in patients with stroke.

PMID- 29456338
TI  - Study of Knowledge, Attitude, and Practice in Participants with Regular Intake of
      Lathyrus, But No Spastic Paraparesis.
AB  - Background and Purpose: Neurolathyrism is now a disease of the past and also the
      causative agent, Lathyrus sativus (Khesari Pulse or keerai in Local Hindi and
      Bhojpuri language) has now been proven to be harmless and has become part of the
      usual diet. Materials and Methods: The population at risk was screened and
      studied for demography, economic status, knowledge about Khesari pulse, awareness
      about so-called harmful effects of Khesari pulse intake in humans, and the
      effects of ban of Khesari pulse on the population which is using Lathyrus
      (Khesari) as a major source of pulse since the past 4 years through a
      questionnaire of three pages. Results: Nearly 97% of total screened population
      totally fed on Khesari pulse as their major source of food and we did not found a
      single case of primary walking difficulty. We did find three cases of poststroke
      paralysis, a case of post-GBS lower limb weakness, and a case of recurrent
      myelitis as a part of questionnaire-based study and then followed by personally
      examining the patients to confirm the diagnosis. Conclusion: Khesari pulse if
      consumed in smaller quantities as a part of a normal mixed diet, its nutritional
      values can be optimally utilized.

PMID- 29456339
TI  - Retrospective Analysis of Arthrodesis from Various Options after Anterior
      Cervical Discectomy.
AB  - Introduction: Anterior cervical discectomy is a surgical procedure performed to
      treat a herniated/degenerated disc in the cervical region. There have been
      various studies comparing arthrodesis rates among various procedures. Our
      patients belonged to varied socioeconomic background and underwent anterior
      cervical microdiscectomy without/with instrumentation. Aim: The present study was
      performed to study and compare the arthrodesis rates in the patients operated for
      anterior cervical microdiscectomy with and without fusion/instrumentation
      procedures at our institution. Materials and Methods: This is a retrospective
      study performed at Vydehi Institute of Medical Sciences and Research Centre,
      Bengaluru. Pre- and post-operative X-rays were assessed in 96 patients who had
      undergone anterior cervical discectomy with/without fusion from June 2012 to June
      2015. Radiographic arthrodesis was assessed in all patients. An arbitrary grading
      was designed by us and categorized into Grade I to IV. The criteria considered
      for adequate arthrodesis in this study were: (a) <2 degrees  movement on dynamic
      X-rays, (b) restored disc space height (+/-2 mm accepted), and (c) evidence of
      solid bone mass around disc space. Arthrodesis was categorized as Grade I if all
      the above 3 criteria on X-rays was fulfilled, Grade II if any 2 of the criteria
      was fulfilled, Grade III if any 1 of the criteria was fulfilled, and Grade IV
      when pseudoarthrosis/none of the criteria was fulfilled. Grade I arthrodesis was
      noted in about 79 patients (82.2%), Grade II in 14 patients, and only 3 patients
      had Grade III arthrodesis. There were no patients with absent
      arthrodesis/pseudoarthrosis. Results: Satisfactory arthrodesis was noted in 82%
      of the total patients, with patients undergoing fusion +/- instrumentation
      procedure having better results. Conclusions: Arthrodesis by an interbody
      graft/implant with/without plating increases chances of success as compared to
      anterior cervical discectomy alone. Patients should be motivated for any of the
      available options for fusion/instrumentation.

PMID- 29456340
TI  - Acute Febrile Encephalopathy in Children: A Prospective Study of Clinical
      Features, Etiology, Mortality, and Risk Factors from Western India.
AB  - Introduction: Acute febrile encephalopathy (AFE) in children is a medical
      emergency and could be a manifestation of many systemic and central nervous
      system pathologies. The clinical features of AFE are nonspecific and etiological
      spectrum variable depending on the studied population. Materials and Methods: A
      prospective, observational study was carried out including children aged between
      1 month and 12 years with AFE admitted to the Pediatric Intensive Care Unit of a
      tertiary care hospital in Western India. The primary objective was to assess the
      clinical presentation and etiology of AFE while the secondary objectives were to
      correlate the clinical and etiological findings and to determine the risk factors
      associated with mortality. Results: Out of the ninety children with AFE included
      in this study, male:female ratio was 1.2:1; most of them were aged between 1 and
      5 years and came with a history of < 7 days (82.2%). All of them had altered
      sensorium, about 2/3rd had seizures and 47.8% having a Glasgow Coma Score (GCS)
      <8. Etiology remained elusive in about 40% of the cases, and viral infections
      were the most common among the ones with an identifiable cause. A variety of
      morbidity (shock, disseminated intravascular coagulopathy, respiratory failure,
      etc.) and high mortality (40%) was observed with risk factors associated with
      mortality being GCS < 8, the presence of raised intracranial pressure, shock, and
      respiratory failure. Conclusion: AFE, though a rare diagnosis in children, is
      associated with significant morbidity and high mortality in a developing country
      like India.

PMID- 29456341
TI  - Using of Fresh Cadaveric Cow Brain in the Microsurgical Training Model for Sulcal
      Cisternal and Fissural Dissection.
AB  - Objective: The aim of this experimental study was to evaluate the feasibility of
      using fresh cadaveric cow brain as in a training model for microsurgical
      dissection of sulcus, cisterns, and fissure. Methods: Experimental
      microneurosurgical activities in this study were performed under the operating
      microscope. Bilateral sylvian cisterns, interhemispheric fissure, and hemispheric
      sulcus of the fresh cadaveric cow brain were used as an interested area for this
      experimental study. The dissection was continued reaching down to the floor of
      the cistern and total dissection of the middle cerebral artery inside the
      cisternal space. The suitability of a cow brain as a training model for sylvian
      fissure microdissection was evaluated as three groups; bad, good, and perfect.
      Results: Ten uncovered fresh cadaveric cow brains were used in this experimental
      feasibility study. The suitability of the experiment for training model was
      evaluated as bad in (1) 10% of the fresh cadaveric cow brains. The suitability
      was found as good in (6) 60% of the procedures. In the remaining (3) 30% of the
      brain dissection, the suitability of the experiment was evaluated as perfect.
      Conclusion: In conclusion, performing the sulcal, cisternal, and fissural
      dissection and protecting the neural and vascular tissue from the mechanical
      bruising effect of metallic microsurgical instruments are feasible as shown in
      this study. We believe that this training model will contribute to the practical
      micro-neurosurgery. Additionally, it provides adequate performance for the
      microsurgical intervention.

PMID- 29456342
TI  - Immune-mediated Neuropathies Our Experience over 3 Years.
AB  - Introduction: Immune-mediated peripheral neuropathy is the term applied to a
      spectrum of peripheral nerve disorders where immune dysregulation plays a role.
      Therefore, they are treatable. We analyzed the cases seen in the past 3 years by
      us and evaluated the clinical, laboratory, and outcome parameters in these
      patients. Patients and Methods: Consecutive patients seen by the authors and
      diagnosed as immune-mediated neuropathy were analyzed for etiology, pathology,
      and outcome assessed. Results: A total of sixty patients, 31 acute and 29 chronic
      neuropathies, were identified. Their subtypes treatment and outcome assessed.
      Males were significantly more in both acute and chronic cases. Miller Fisher 4,
      AMAN 1, paraplegic type 1, motor dominant type 19, Sensory-motor 1, MADSAM 3,
      Bifacial 2. Nonsystemic vasculitis was seen in 16 out of 29 chronic neuropathy
      and HIV, POEMS, and diabetes mellitus one each. Discussion: There is a spectrum
      of immune-mediated neuropathy which varies in clinical course, response to
      treatment, etc., Small percentage of uncommon cases are seen. In this group,
      mortality was nil and morbidity was minimal. Conclusion: Immune-mediated
      neuropathies are treatable and hence should be diagnosed early for good quality
      outcome.

PMID- 29456343
TI  - Factors Influencing Institutional-Based Pediatric Rehabilitation Services among
      Caregivers of Children with Developmental Delay in Southwestern Rajasthan.
AB  - Context: A limited number of caregivers of children with developmental delay
      access rehabilitation facilities in India. The study explored utilization of
      rehabilitation services at a tertiary care setup in southwestern Rajasthan and
      various factors influencing it. Aims: The aim of this study is to explore
      rehabilitation service utilization among children with developmental delay at a
      tertiary care setup and to ascertain factors that influence this pattern.
      Settings: This study was conducted at the department of physical medicine and
      rehabilitation at tertiary care setup. Design: This was an observational study.
      Subjects and Methods: Children with developmental delay who were advised
      institutional-based rehabilitation were identified over span of 1 year. Those who
      failed to return for rehabilitation after the first visit were interviewed
      telephonically. The interview had semi-structured open-ended questions about
      their reasons for inability to avail services. Statistical Analysis: SPSS
      statistics 22 was used for descriptive analysis and correlation of variables.
      Results: Of 230 children with developmental delay visiting department in 1-year
      duration, 48 took regular rehabilitation. Parents of 129 children with complete
      records were asked regarding discontinuation. Factors cited by majority were long
      distance from institute and service at hospital. Other reasons for
      discontinuation were related to belief system, family issues, time issues,
      socioeconomic factors, etc. Socioeconomic status was significantly associated
      with parental education (C = 0.488, P = 0.000) and financial issues. Location of
      family had significant association with long distance (C = 0.315, P = 0.000),
      parental education (C = 0.251, P = 0.003), and belief system (C = 0.265, P =
      0.002). Conclusions: Distance from institute and quality of hospital service
      determined rehabilitation service use at a tertiary institute. Other factors such
      as socioeconomic status, family support, and social belief system must also be
      addressed while delivering institutional rehabilitation to children.

PMID- 29456344
TI  - Hansen's Neuritis Revisited - A Clinicopathological Study.
AB  - Introduction: Leprosy affecting the nerve solely or with concomitant skin lesions
      is not an uncommon condition in clinical practice. It is responsible for
      extensive morbidity and often poses a diagnostic challenge. This study aims to
      highlight the clinicopathological features of Hansen's neuritis (HN). Materials
      and Methods: In this retrospective study, cases of histologically diagnosed HN,
      from January 2010 to July 2017, were reviewed in the light of clinical features,
      treatment history, and outcome. Results: There were 18 cases of HN which
      accounted for 3.97% of total nerve biopsy samples (n = 453) and 0.02% of total
      histopathology samples (n = 81,013). The male: female ratio was 5:1 in the cases
      of HN. Age range was 20-79 years with a mean age of 42.4 years (standard
      deviation: +/-14.03). Among the HN cases, there were 13 cases of pure neuritic
      leprosy (61.1%). Mononeuritis multiplex was the most common finding in the nerve
      conduction study. Six (33.3%) cases exhibited histological features of borderline
      tuberculoid leprosy, followed by five (27.8%) cases of mid-borderline features,
      three (16.7%) cases each of borderline lepromatous and burnt-out HN, and one
      (5.6%) case of polar tuberculoid leprosy. Lepra bacilli were detected on Fite
      Faraco stain in 44.4% cases. Conclusion: Diagnosis of HN depends on astute search
      for skin lesions, nerve thickening or tenderness, sensory or motor symptoms,
      histopathological examination, and demonstration of lepra bacilli.

PMID- 29456345
TI  - Rates and Correlations of Psychiatric Drug Administration in a Rehabilitation
      Center.
AB  - Background: Physical injury has been associated with the development of several
      psychopathological manifestations. Less is known about the use of psychiatric
      medication in those patients. Objectives: This study aimed to explore the use of
      psychiatric medication by patients been admitted in a rehabilitation center in a
      tertiary care teaching hospital and to inquire for the correlations of such drug
      administration. Materials and Methods: The sample consisted of 127 patients who
      had been admitted to a rehabilitation center, being in the postacute phase of
      their condition during a 2-year period. Patients' medical records were searched
      for the demographic and clinical information. Results: Analysis was performed for
      118 patients, mostly men (62.7%) with the mean age of 57.5 years. About 43.2% of
      patients (n = 51) were referred for psychiatric consultation, and 39.8% (n = 47)
      were prescribed a psychiatric drug. Traumatic brain injury was the diagnosis,
      positively correlated to referral. Twenty-seven out of the 67 nonreferred
      patients (40.3%) were prescribed psychiatric regimens by physicians. Nearly 38.1%
      of patients were diagnosed with a psychiatric disorder by the consultation
      Liaison psychiatric service. Conclusions: In a rehabilitation center, psychiatric
      drug administration is common practice and drugs may be prescribed by the
      center's physicians and by psychiatrists. Such a drug prescription was found to
      be correlated to referral to the consultation-Liaison psychiatric service.

PMID- 29456346
TI  - The Effects of Posterior Talar Glide and Dorsiflexion of the Ankle Plus
      Mobilization with Movement on Balance and Gait Function in Patient with Chronic
      Stroke: A Randomized Controlled Trial.
AB  - Background: This study was to evaluate the effects of weight-bearing-based
      mobilization with movement (WBBMWM) on balance and gait in stroke patients.
      Methods: Thirty stroke patients participated in this study. All individuals were
      randomly assigned to either WBMWM group (n = 15) or weight-bearing with placebo
      mobilization with movement group (control, n = 15). Individuals in the WBMWM
      group were trained for 10 glides of 5 sets a day, 5 times a week during 4 weeks.
      Furthermore, individuals in the control group were trained for 10 lunges of 5
      sets a day, 5 times a week during 4 weeks. All individuals were measured weight
      bearing lunge test (WBLT), static balance ability, timed up and go test (TUG),
      and dynamic gait index (DGI) in before and after intervention. Results: The
      result showed that WBBMWM group and control group had significantly increased in
      WBLT, postural sway speed, total postural sway path length with eyes open and
      closed, TUG and DGI (P < 0.05). In particular, the WBMWM group showed
      significantly greater improvement than control group in WBLT, static balance
      measures, TUG, and DGI (P < 0.05). Conclusion: Therefore, WBMWM improved ankle
      range of motion, balance, and gait in stroke patients. These results suggest that
      WBBMWM is feasible and suitable for individuals with a stroke.

PMID- 29456347
TI  - The Evolving Pattern and Outcome of Stroke at Moderate Altitude.
AB  - Background: The people residing in hills of this Sub-Himalayan region
      traditionally have a distinct lifestyle involving high level of physical
      activity. However, increased urbanization in the last two decades has led to
      changes in lifestyle of people. The present study was an endeavor to document
      changes in the pattern of stroke in people residing at moderate altitude. Aim:
      This study was aimed to study the evolving trends in clinical profile, risk
      factors, and outcome at 3 months in hospitalized patients of stroke in a Tertiary
      Care Hospital situated at moderate altitude. Setting and Design: This
      prospective, observational study was carried out in a Tertiary Care Hospital,
      situated at 2000 m mean sea level, from July 2014 to June 2015 in Sub-Himalayan
      region of India. Methods: The clinical features and risk factors profile of 235
      patients of stroke consecutively admitted in hospital were analyzed, and findings
      were expressed in percentage. The profile was compared with a study conducted at
      this institute 15 years back. The outcome of patients at 3 months in terms of
      modified Rankin Scale >3 (mRS) and Barthel Index <60 (BI) was also studied.
      Results: The occurrence of stroke as a cause of hospitalization was decreasing.
      Ischemic stroke was noted in 74%, and 26% had hemorrhagic stroke (HS). There was
      male predominance (58%), but affliction of females with stroke increased from 34%
      to 42%. The altered sensorium (P = 0.00) and neurological weakness (P = 0.024)
      were significantly associated with poor outcome in stroke. The occurrence of
      hypertension, diabetes mellitus, and coronary artery disease increased but
      smoking decreased among indoor patients of stroke in the last 15 years. Poor
      outcome of 203 patients at 3 months follow-up in terms of mRS >3 was 79 (IS-47,
      HS-32) but in term of BI, 63 (IS-32, HS-31) had poor outcome. Overall HS had
      poorer outcome. Age >70 years, female sex, altered sensorium, hypertension, and
      diabetes mellitus, were observed as poor prognostic factors, but the association
      was significant with advanced age, headache, and altered sensorium. Conclusion:
      The occurrence of stroke decreased among hospitalized patients. Hypertension,
      diabetes mellitus, and coronary artery disease increased but smoking decreased
      among patients of stroke.

PMID- 29456348
TI  - Efficacy of Dexmedetomidine as an Adjuvant to Local Anesthetic Agent in Scalp
      Block and Scalp Infiltration to Control Postcraniotomy Pain: A Double-Blind
      Randomized Trial.
AB  - Context: Scalp infiltration and scalp block are being used to manage
      postcraniotomy pain. Dexmedetomidine has been successfully used as an adjuvant in
      regional anesthesia. The study was intended to compare whether addition of
      dexmedetomidine prolonged the duration of analgesia as well as to compare the two
      techniques. Aims: The primary objective was to assess whether addition of
      dexmedetomidine to bupivacaine prolonged the duration of analgesia. The secondary
      objective was to compare between scalp nerve block and scalp infiltration as
      techniques for pain relief. Settings and Design: The randomized control study was
      conducted in a tertiary care center from November 2013 to October 2014. Materials
      and Methods: A total of 150 American Society of Anesthesiologists Physical Status
      I-II patients, aged 18-70 years undergoing elective craniotomy were included.
      Patients were randomized into three groups of 50 patients, i.e., Group BI
      (bupivacaine infiltration), Group BDI (bupivacaine and dexmedetomidine
      infiltration), and Group BDNB (bupivacaine and dexmedetomidine scalp nerve
      block). Patient's pain score, pain-free interval, rescue analgesic requirement,
      and hemodynamic and respiratory parameters were noted for 48 h. Patients were
      followed up at 1 and 3 months to assess postcraniotomy pain. Results: Pain-free
      period was significantly longer in Group BDNB than Groups BDI and BI (P < 0.0001)
      and pain control was better in dexmedetomidine containing groups than in
      bupivacaine group (BI) (P < 0.0001). The rescue analgesic requirement was
      significantly lower in Group BDNB and Group BDI compared to Group BI. Conclusion:
      The addition of dexmedetomidine (1 MUg/kg) to bupivacaine prolonged the pain-free
      period. Scalp nerve block is a superior technique than scalp infiltration.

PMID- 29456349
TI  - Effects of Crystalloid Preloading (20 ml/kg) on Hemodynamics in Relation to
      Postural Changes in Patients Undergoing Neurosurgical Procedures in Sitting
      Position.
AB  - Background: Hemodynamic disturbances are common during positioning the patients
      from supine to sitting for neurosurgical procedures. The reported incidence of
      hypotension varies from 5% to 32%. The aim of the study was to study the effect
      of crystalloid preloading on hemodynamic parameters during positioning the
      patient from supine to sitting position. Materials and Methods: In this
      prospective observational trial, 20 patients were enrolled. Two patients had a
      patent foramen ovale on transesophageal echocardiography and were excluded from
      the study. All the patients received 20 ml/kg of crystalloid (Ringer's lactate)
      before initiation of positioning. Physiological hemodynamic parameters such as
      heart rate, mean arterial pressure, central venous pressure, cardiac output (CO),
      stroke volume variation (SVV), cardiac index (CI), stroke volume (SV), and
      maximum and minimum inferior vena caval diameter (IVCD) were recorded after
      induction, during positioning at 30 degrees , 60 degrees  inclination of the
      operating table and after the final sitting position. Results: Hemodynamic
      parameters were well maintained during positioning of the patients from supine to
      sitting position. Crystalloid preloading prevented the hypotension during
      positioning. There were no significant changes in hemodynamic parameters such as
      CO, SVR, SVV, CI, and SV. We did not find any correlation with changes in IVCD
      with changes in CO. Conclusion: A volume of 20 ml/kg of crystalloid preloading
      before positioning the patient from supine to sitting position maintains the
      hemodynamic stability and avoids the vasopressor requirement.

PMID- 29456350
TI  - Recurrent Glioblastomas Exhibit Higher Expression of Biomarkers with Stem-like
      Properties.
AB  - Background: Despite advances in the treatment of glioblastoma (GBM), the
      prognosis of patients continues to remain dismal. This unfavorable prognosis is
      mainly attributed to the tumor's propensity for progression and recurrence, which
      in turn is due to the highly aggressive nature of the persisting GBM cells that
      actively egress from the main tumor mass into the surrounding normal brain
      tissue. Such a recurrent tumor described to have a more malignant potential is
      highly invasive and resistant to current therapies, probably due to increased
      stemness and preferential selection of therapy-resistant clones of tumor cells.
      However, there is a paucity of literature on the expression of biomarkers in the
      recurrent GBM tumors that could have a role in conferring this aggressiveness.
      Aim: To identify the differences in the expression pattern of selected biomarkers
      in paired tissue samples of GBM. Material and Methods: A retrospective study on
      30 paired samples of GBM (newly diagnosed/primary and recurrent) archived in the
      Department of Neuropathology, NIMHANS (2006-2009), was carried out. After
      obtaining clinical and demographic details, tumors were characterized
      histomorphologically and immunohistochemically on formalin-fixed paraffin
      embedded tissues with reference to expression of biomarkers such as p53,
      epidermal growth factor receptor (EGFR), insulin-like growth factor binding
      protein 3 (IGFBP-3), sex determining region Y-box 2 (SOX2), and topoisomerase 2 A
      (Top2A). The results were statistically analyzed. Results: It was observed that
      while p53 and IGFBP-3 expression remained unaltered in paired samples, a
      significant increase in the expression of EGFR (P < 0.01) was noted in the
      recurrent tumors. Among the other biomarkers, SOX2 expression was higher in the
      recurrent tumors when compared to the primary tumors (P < 0.01). Conversely, the
      expression of Top2A was reduced in recurrent tumors (P = 0.05). Mild elevation in
      the expression of IGFBP-3 was observed in recurrent tumors but was not
      statistically significant. Conclusion: A significant increase in the expression
      of SOX2 in recurrent tumors probably indicates the presence of undifferentiated
      cells with stem-like properties in these tumors. EGFR is known to mediate SOX2
      expression thereby resulting in stemness of the glioma cancer cells, which could
      further explain its overexpression in recurrent GBMs. Furthermore, a decreased
      expression of TOP2A observed in the recurrent tumors could probably be due to
      reduction in chemosensitivity to temozolomide, which has been shown in earlier
      studies. We also noted that p53 expression remained unaltered in the recurrent
      tumors when compared to the primary, suggesting the absence of preferential
      clonal expansion of p53 mutant cells following exposure to radiochemotherapy. Our
      study reiterates the fact that GBM recurrences are associated with molecular
      alterations that probably contribute to radiochemoresistance, increased
      invasiveness, therapeutic efficacy, and stemness.

PMID- 29456351
TI  - Quality of Sleep and Sleep Disorders in Patients with Parkinsonism: A
      Polysomnography Based Study from Rural South India.
AB  - Objective: The objective of this study is to study the quality of sleep, sleep
      disorders, and polysomnographic profile in Parkinsonism patients from rural areas
      and to correlate polysomnographic profile with the staging of disease and with
      sleep questionnaire. Materials and Methods: Between May 2014 and December 2015,
      168 Parkinsonism patients were prospectively screened using sleep questionnaire;
      Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Parkinson
      Disease Sleep Score-2 (PDSS-2). Sixty patients underwent overnight
      polysomnography subsequently. Results: The mean age of 168 patients in the study
      was 65.3 +/- 12.8 years. The mean duration of Parkinsonism was 4.6 +/- 3.1 years.
      The mean ESS, PSQI and PDSS-2 were 12.4 +/- 3.2, 7.9 +/- 2.1 and 44.7 +/- 5.8,
      respectively. A total of 148 patients (88.1%) had poor quality sleep, which was
      reported only in 37 patients (22%). Excessive daytime sleepiness (80%) and
      insomnia (76.7%) were most common symptoms. Polysomnographic profile showed poor
      sleep efficiency (median interquartile range [IQR] 74.8% [17.8%-99.5%]), reduced
      slow wave sleep (median [IQR] 0% [0%-9.5%]), and reduced rapid eye movement [REM]
      sleep (median (IQR) 4.9% [0.1%-24.2%]). Sleep disorders in the study were sleep
      fragmentation (n = 60, 100%), obstructive sleep apnea syndrome (n = 40, 66.7%),
      central sleep apnea syndrome (n = 6, 10%), and periodic limb movement disorder (n
      = 52, 86.7%). Two patients had REM sleep behavioral disorder clinically. There
      was statistically significant positive correlation between staging of disease,
      sleep latencies, and sleep questionnaire. Conclusion: Sleep is impaired in
      majority of Parkinsonism patients which needs to be diagnosed early and managed
      effectively. Patient education and awareness programs in rural areas regarding
      sleep disorders in Parkinsonism are required for early diagnosis.

PMID- 29456352
TI  - Efficacy of Botulinum Toxin Type A in Trigeminal Neuralgia in a South Asian
      Cohort.
AB  - Introduction: The antinociceptive effect of botulinum toxin-A (BTX-A) in
      trigeminal neuralgia (TN) has been described. We evaluated effects of BTX-A in
      relieving pain in patients with refractory TN at National Hospital of Sri Lanka.
      Materials and Methods: Pain in patients with TN was assessed using a visual
      analog from 0 to 10. Three months after commencement of drug therapy with >=2
      drugs including one first-line drug (carbamazepine/oxcarbazepine), pain scores
      were re-assessed. Twenty-two patients who did not report improvement of >=50% at
      90 days' posttreatment were recruited. They were given adjunct BTX-A directly to
      the trigger point (if identified) or intradermal. Pain scores were assessed at
      10, 20, 30, 60, and 90 days' posttreatment. Results: There was a statistically
      significant improvement in mean pain scores at 10, 20, 30, 60, and 90 days'
      posttreatment (5.59 [standard deviation (SD) = 2.7], 5.68 [SD = 2.6], 5.27 [SD =
      3.2], 4.77 [SD = 3.7], and 5.32 [SD = 4.0]) compared to pre-BTX-A treatment
      (7.14, SD = 2.2). Percentage reduction in mean pain score ranged from 20.4% to
      33.1%. Maximum response was at day 60 post-BTX-A (50% had >=50% reduction in
      pain). No significant difference was found in response with higher doses and
      injection strategy. Conclusion: Consistent statistically significant reductions
      in pain scores at the aforesaid intervals compared to pretreatment means that
      there is a place for BTX in refractory TN.

PMID- 29456353
TI  - The Utility of Preoperative ACTH/Cortisol Ratio for the Diagnosis and Prognosis
      of Cushing's Disease.
AB  - Purpose: Cushing's syndrome (CS) is a rare disease having diagnostic
      difficulties. Many diagnostic tests have been defined but none of these are
      diagnostic alone. Determination of the cause is another problem which sometimes
      requires more sophisticated and invasive procedures. Therefore, we aimed to
      evaluate the utility of pretreatment plasma adrenocorticotropic hormone
      (ACTH)/cortisol ratios in patients with confirmed endogenous CS for the diagnosis
      and differential diagnosis of CS. Materials and Methods: This retrospective
      evaluation included 145 patients with the diagnosis of CS, 119 patients with
      Cushing's disease (CD), and 26 patients with ACTH-independent CS (AICS), in a
      university hospital. Furthermore, 114 individuals in whom CS diagnosis was
      excluded with at least one negative screening test were enrolled to the study as
      control group. The clinical, laboratory, imaging, postsurgical pathologic records
      and also clinical follow-up data of all patients were evaluated. Results: The
      median basal ACTH/cortisol ratio of the patients with CD was significantly higher
      than AICS and controls. A cutoff ACTH/cortisol ratio >2.5 was found to be
      diagnostic for CD with 82% specificity and 63% sensitivity. Among CD group,
      patients with recurrent disease had higher preoperative ACTH levels and
      ACTH/cortisol ratio than patients with sustained remission. Furthermore, these
      patients had more invasive, atypical, and larger tumors. Conclusion: An
      ACTH/cortisol ratio >2.5 would be beneficial to diagnose CD together with other
      diagnostic tests. It is a simple test with no additional cost. Higher ratios
      might be related with larger, invasive, and atypical adenoma and also might be
      helpful to predict recurrence.

PMID- 29456354
TI  - Impact of Aging on Nerve Conduction Velocities and Late Responses in Healthy
      Individuals.
AB  - Background: Nerve conduction studies are performed to diagnose the disorders of
      the peripheral nervous system. The reference values for nerve conduction velocity
      (NCV) and late responses for different nerves considerably vary in different
      group and type of population. Physiological factors such as age, temperature,
      height, and gender affect the NCV. However, there are very few studies which show
      the age group at which these changes become significant. Aim and Objectives: The
      aim of the study was to establish the electrophysiological data of the specific
      age group at which changes in NCV as well as late responses of median common
      peroneal nerve and also see the late response in the form of F-waves and H
      reflex. Methodology: Study groups were divided into three categories based on the
      age: Group I (18-30 years) (n = 80), Group II (31-45 years) (n = 43), and Group
      III (46-60 years) (n = 27). Out of which, 93 patients were male and 57 were
      female. The NCVs were determined for median, common peroneal nerve (motor
      component and sensory component) along with late responses in the form of H
      reflex and F-waves. Results: The mean and standard deviation of median, ulnar,
      peroneal, and tibial nerve was studied for latencies, amplitude, and velocities
      for both sensory and motor components. Patients with older age had longer
      latencies, smaller amplitudes, and slower conduction velocities compared with the
      younger age group. The change with age was greater in sensory nerve conduction
      and late responses in all the peripheral nerves. Conclusions: Aging has a
      definite correlation with the NCV and late responses of different peripheral
      nerves. There is a need to have reference values with relation to age.

PMID- 29456355
TI  - Role of Yoga in Management of Substance-use Disorders: A Narrative Review.
AB  - Substance use disorders are comparable to chronic medical illnesses and have a
      chronic relapsing course. Despite being significant contributors to morbidity and
      mortality, limited treatment options exist. The current narrative review was
      aimed at providing an overview of yoga therapy in substance-use disorders and
      discuss the relevant methodological issues. Articles published in English
      language till May 2017 indexed with PubMed, PubMed central, and Google Scholar
      were searched using search terms "Yoga," "Substance use," "Drug dependence,"
      "Nicotine," "Tobacco," "Alcohol," "Opioids," "Cannabis," "Cocaine," "Stimulants,"
      "Sedative hypnotics," "Inhalants," and "Hallucinogens" for inclusion in the
      review. A total of 314 studies were found fulfilling the stated criteria. Out of
      which, 16 studies were found to fulfill the inclusion and exclusion criteria and
      12 were randomized control trials. The majority of studies were available on the
      role of yoga in management of nicotine dependence. Sample size of these studies
      ranged from 18 to 624. The majority of studies suggested the role of yoga in
      reducing substance use as well as substance-related craving (especially in
      nicotine-use disorders) in short term. However, more studies are required for
      demonstrating the long-term effects of yoga therapy in substance-use disorder.

PMID- 29456356
TI  - The Current State of Rural Neurosurgical Practice: An International Perspective.
AB  - Introduction: Rural and low-resource areas have diminished capacity to care for
      neurosurgical patients due to lack of infrastructure, healthcare investment, and
      training programs. This review summarizes the range of rural neurosurgical
      procedures, novel mechanisms for delivering care, rapid training programs, and
      outcome differences across international rural neurosurgical practice. Methods: A
      comprehensive literature search was performed for English language manuscripts
      with keywords "rural" and "neurosurgery" using the National Library of Medicine
      PubMed database (01/1971-06/2017). Twenty-four articles focusing on rural non
      neurosurgical practice were included. Results: Time to care and/or surgery and
      shortage of trained personnel remain the strongest risk factors for mortality and
      poor outcome. Telemedicine consults to regional centers with neurosurgery
      housestaff have potential for increased timeliness of diagnosis/triage, improved
      time to surgery, and reductions in unnecessary transfers in remote areas. Mobile
      neurosurgery teams have been deployed with success in nations with large
      transport distances precluding initial transfers. Common neurosurgical procedures
      involve trauma mechanisms; accordingly, training programs for nonneurosurgery
      medical personnel on basic assessment and operative techniques have been
      successful in resource-deficient settings where neurosurgeons are unavailable.
      Conclusions: Protracted transport times, lack of resources/training, and
      difficulty retaining specialists are barriers to successful outcomes. Advances in
      telemedicine, mobile neurosurgery, and training programs for urgent operative
      techniques have been implemented efficaciously. Development of guidelines for
      paired partnerships between rural centers and academic hospitals, supplying
      surplus technology to rural areas, and rapid training of qualified local surgical
      personnel can create sustainable feed-forward programs for trainees and
      infrastructural solutions to address challenges in rural neurosurgery.

PMID- 29456357
TI  - Role of Exclusive Breastfeeding in Conferring Protection in Children At-Risk for
      Autism Spectrum Disorder: Results from a Sibling Case-control Study.
AB  - Background: Gut microflora influences neural development through complex
      mechanisms. Feeding practices, especially breastfeeding influence gut microbiome
      and thereby play a pivotal role in immune and neural development. Current
      understandings of the role of healthy distal gut microflora in the development of
      immune and neural systems provide insights into immunological mechanisms as one
      of the possible etiologies in autism spectrum disorder (ASD). Studies have shown
      that optimal breastfeeding is associated with lower odds of being at-risk for ASD
      and children with ASD are suboptimally breastfed. Methods: The feeding practices
      of children with ASD (n = 30) was compared to their typically developing siblings
      as matched controls (n = 30). Information regarding feeding practices was
      collected from mothers through a semi-structured questionnaire. Results: About
      43.3% of children with ASD received exclusive breastfeeding, whereas 76.7% of
      their typically developing siblings were exclusively breastfed. Exclusive
      breastfeeding was associated with lower odds for ASD (odds ratio [OR] = 0.166;
      95% confidence interval [CI] = 0.025-0.65), while early introduction of top feeds
      was associated with higher odds (OR = 6; 95% CI = 1.33-55.19). Difficulties in
      breastfeeding were attributed to child-related factors in 13.2% of the children.
      Conclusion: Children with ASD are suboptimally breastfed compared to their
      typically developing siblings. Exclusive breastfeeding may confer protection in
      vulnerable children. Further studies on larger prospective sample are required to
      establish the association.

PMID- 29456358
TI  - Surgically Treated Primary Spinal Cord Neoplasms in Southeastern Nigeria.
AB  - Background: Primary spinal cord tumors are not as frequently encountered as their
      cranial counterparts. They could present in such an indolent manner that requires
      a reasonable index of suspicion for their diagnosis to be considered. Objective:
      The objective of this study is to analyze the incidence and pattern of primary
      spinal cord and appendage neoplasms in patients surgically treated in our
      institution over a decade of practice. Materials and Methods: A retrospective
      review of clinical, radiological, and histopathology profiles of patients
      surgically treated for primary spinal cord tumor from 2006 to 2016 was carried
      out. Retrieved data were analyzed using SPSS version 21. Results: Out of 472
      spine procedures were performed within the study period 17 (3.6%) cases of
      histologically proven primary spinal cord tumors were identified. The age of
      patients ranged between 17 and 77 years with a mean age was 45 years. The male:
      female ratio was 1:1.1. Motor deficit and pain were the most common presenting
      symptoms seen in 35.3% and 29.4% of patients, respectively. Meningiomas are the
      most common histological diagnosis (70.6%), distantly followed by Schwannoma
      (17.6%). The most common location of the tumors was intradural extramedullary
      (70.6%). All patients had gross total resection of tumor with no perioperative
      mortality. Conclusion: Meningioma is the most common surgically treated primary
      spinal cord tumor in our setting. Surgery is associated with good outcome.

PMID- 29456359
TI  - Comparison of Computerized and Standard Cognitive Test in Thai Memory Clinic.
AB  - Background: Computer-based Thai Cognitive Test or Computer-based Thai Mental
      State Examination (cTMSE) was developed aiming to help doctors to easily get the
      accurate results of TMSE in a routine, busy outpatient clinics. The purpose of
      this study was to compare the evaluation process in terms of feasibility,
      duration of the test, participants/administrator preference, and the results of
      cognitive test between cTMSE and the standard Thai Mental State Examination
      (sTMSE). Methods: Twenty-two elderly participants (>60 years old) who were not
      demented and 22 patients with mild-to-moderate dementia were included in the
      study. All participants would be asked to have TMSE by standard method (sTMSE)
      and computer-based method (cTMSE), at least 2 weeks and up to 2 months apart.
      Scores and duration of the test were compared using dependent paired t-test.
      Agreement of the tests between two methods and Kappa statistics were analyzed.
      Results: Paired t-test showed no significant difference in scores between the two
      methods (mean sTMSE vs. cTMSE: 22.84 vs. 22.62, 95% confidence interval [CI]: [
      0.465] to 0.987, P = 0.524). Percent of agreement between the two methods was
      92.5%, with the Kappa of 0.85 (P < 0.001). Duration of the test by sTMSE was
      slightly shorter than the cTMSE (7.31 min vs. 7.97 min, 95% CI: [-1.159] to [
      0.175], P = 0.09). Overall, participants liked being tested by cTMSE more than
      sTMSE. Conclusion: Computer-based TMSE was feasible to use and accurate for
      screening in aging adults and for cognitive evaluation in patients with mild-to
      moderate dementia.

PMID- 29456360
TI  - Clinical Features and Psychiatric Comorbidity of Epicrania Fugax.
AB  - Background: Epicrania fugax (EF) is a rare newly described primary headache
      characterized by paroxysms of unilateral pain radiating across one hemicranium.
      Aim: We aimed to describe 10 new cases of EF and assess the psychiatric
      comorbidity. Materials and Methods: Cases of EF were identified from patients
      attending the neurology outpatient department of a tertiary level referral and
      teaching hospital by the first author during a period extending from January 1,
      2015 to April 31, 2017. Case ascertainment was done as per ICHD 3 beta criteria
      from among patients presenting with complaints of headache after detailed history
      and clinical examination. Clinical and demographic features were noted and
      patients were subjected to Mini Neuropsychiatric Interview to screen for
      psychiatric comorbidity followed by Becks Anxiety/Depression Inventory. Results:
      A total of 10 subjects were obtained during the study period, 4 males, and 6
      females. Mean age of subjects was 45.3 years (standard deviation-10). Seventy
      percent had anteroposterior, and 30% had posteroanterior radiation of pain. The
      most common character of pain was stabbing (50%) followed by electrical (40%) and
      pressing (10%). None of the subjects had autonomic symptoms or focal symptoms in
      the scalp while 30% subjects had hyperesthesia in the affected area of the scalp.
      Six subjects (60%) patients had episodic course while 40% had chronic course.
      Sixty percent had comorbid anxiety while one (10%) had comorbid depression. A
      significant relation was obtained between duration of disease and occurrence of
      anxiety as well as Becks Anxiety Inventory scores while there was no correlation
      with attack duration. There was also a nonsignificant correlation between visual
      analog score and occurrence of anxiety symptoms. Conclusions: Our study
      conclusively proves the existence of EF as a rare, distinct primary headache
      syndrome in our study population. It has a significant psychiatric comorbidity
      consisting of 60% of generalized anxiety disorder, 10% of panic attacks, and 10%
      of depression.

PMID- 29456362
TI  - Joubert Syndrome with Orofacial Digital Features.
AB  - Joubert syndrome (JS) is an autosomal recessive inherited disorder characterized
      by hypotonia, cerebellar vermis hypoplasia, ocular abnormalities (e.g.,
      pigmentary retinopathy, oculomotor apraxia, and nystagmus), renal cysts, and
      hepatic fibrosis. Respiratory abnormalities, as apnea and hyperpnea, may be
      present, as well as mental retardation. Since the clinical findings of JS are
      quite heterogeneous, determination of radiological findings is essential.

PMID- 29456361
TI  - Upper Cervical Bronchogenic Cyst: A Rare Condition at a Rare Location.
AB  - Intraspinal bronchogenic cyst (SBC) is a rare but important cause of spinal cord
      compression, commonly seen in the cervicothoracic spine. We report a case of a 43
      year-old male, presenting with complaints of neck pain, radiating to right
      shoulder, with numbness of right hand and fingers. Magnetic resonance imaging of
      the cervical spine revealed an intradural extramedullary, ventral cystic lesion
      extending from C2 to C4 vertebral levels. Complete surgical excision was
      performed, and the patient had a complete relief of symptoms postoperatively.
      Only 11 cases of SBCs have been reported in literature. We discuss the peculiar
      location of this lesion, possible embryological reasons and the overall surgical
      outcome of SBC.

PMID- 29456363
TI  - Inadvertent Central Arterial Catheterization: An Unusual Cause of Ischemic
      Stroke.
AB  - Central venous catheter (CVC) insertion is extensively utilized in Intensive Care
      Units for evaluation of hemodynamic status, administration of intravenous drugs,
      and for providing nutritional support in critically ill patients. Unfortunately,
      CVC use is associated with complications including lung injury, bleeding,
      infection, and thrombosis. We present a patient with an acute ischemic stroke
      from an inadvertently placed CVC into the right common carotid artery. A 57-year
      old male presented to our institution for left hemiplegia and seizures 2 days
      after a CVC was placed. He was found to have a right frontal ischemic stroke on
      computed tomography (CT). CT angiography noted that the catheter was arterial and
      had a thrombosis around it. He was started on a low-dose heparin infusion. A
      combination of cardiothoracic surgery and interventional cardiology was required
      to safely remove the catheter. Central arterial catheterization is an unusual
      cause for acute ischemic stroke and presents management challenges.

PMID- 29456364
TI  - Radiologically Indistinguishable Contiguous Meningioma and Schwannoma in the Same
      Cerebellopontine Angle in a Patient with NF2: Case Report and Literature Review.

PMID- 29456365
TI  - Dyspraxic Gait due to Right Posterior Cerebral Artery Stroke.

PMID- 29456367
TI  - Serial Diffusion-Weighted Imaging in Transient Global Amnesia?

PMID- 29456366
TI  - Delicate Situation of Bipolar Disorder and Interferon Therapy.

PMID- 29456368
TI  - Irreversible Hypersomnolence after Bilateral Thalamic Infarction.

PMID- 29456369
TI  - Commentary.

PMID- 29456370
TI  - Prolactin Secreting Pituitary Carcinoma with Extracranial Spread Presenting with
      Pathological Fracture of Femur.

PMID- 29456371
TI  - Rarely Encountered, Seldom Considered: Posterior Tibial Nerve Schwannoma
      Mimicking Lumbar Radiculopathy.

PMID- 29456372
TI  - Drug-drug Interaction-related Uncontrolled Glycemia.
AB  - Context: The literature of drug-drug interaction (DDI)-related uncontrolled
      causality, and preventability of DDI-induced UCG (HbA1c >7%) in outpatients
      glycemia (UCG) among outpatients with Type 2 diabetes mellitus is still limited.
      Aims: The aim of this study is to identify the prevalence, mechanism, severity,
      with Type 2 diabetes. Settings and Design: A cross-sectional study was conducted
      in Penang General Hospital. Methods: A computerized system for DDI checking was
      used to assess the severity and mechanism of DDIs. Drug interaction probability
      scale was used to evaluate the likelihood of DDIs. Preventability of DDIs has
      been determined by the instrument of Hallas. The UCG prevalence related to DDIs
      was further assessed. Statistical Analysis Used: SPSS 21.00 was used in this
      study. Results: From 425 outpatients with HbA1c% test, their mean age was 58.7 +/
      12.8 years. Only 225 (52.9%) cases had controlled glycemia while 200 (47.1%)
      cases with UCG. They had multiple comorbidities, with a mean number of 3.8 +/-
      2.2/patient and often prescribed with multiple medications, with a mean number of
      6.33 +/- 4.67/patient. It has been detected that 86 DDIs causing UCG in 46
      patients (23%) with range of (1 - 4) DDIs per patient. Drugs with DDI-induced UCG
      were as follows: diuretics (79%), salbutamol (9.2%), cortisones (5.8%), and
      others (6%). The majority of these DDIs were categorized as possible (77.9%) and
      preventable (37%). Conclusion: Nearly one-quarter of UCG was induced by DDIs;
      most of these DDIs are possible, and more than one-third are preventable. It was
      concluded that thiazide diuretics have the highest prevalence of DDI-related UCG.

PMID- 29456373
TI  - Quality of Life among Patients Undergoing Hemodialysis in Penang, Malaysia.
AB  - Background: Quality of life is one of the parameters to check the improvement of
      hemodialysis treatment among hemodialysed patients. Those patients will be
      dealing with this treatment in long term if this treatment is the only way for
      them to replace their kidney function and this thing will affect their quality of
      life. Objective: To evaluate the quality of life patients on hemodialysis using
      kidney disease quality of life-short term 24 (KDQoL-SF24) Malaysian Version.
      Materials and Methods: Cohort observational study was conducted in this study.
      The study included 78 hemodialysed patients in HD center Penang, Malaysia.
      Results: There were 9 components which had the lower of the mean and standard
      deviation (SD) than the standard form; work status (15.01 +/- 35.57), cognitive
      function (75.66 +/- 13.75), quality of life social interaction (76.32 +/- 16.11),
      sleep (55.86 +/- 15.30), social support (59.61 +/- 22.08), patient satisfaction
      (43.24 +/- 15.32), physical functioning (50.06 +/- 42.81), general health (29.62
      +/- 25.56), and role emotional (54.27 +/- 49.92). In this HD center, the group of
      patient's age who had the lower mean +/- SD from the KDQoL-SF Manual Standard
      were the first and the sixth groups of patient's age (<=20 and 61-70).
      Conclusion: The study conducted in HD center, Penang, Malaysia showed that the
      scoring of work status, cognitive function, quality of social interaction, sleep,
      social support, patient satisfaction, physical functioning, general health, and
      role emotional were low than standard form.

PMID- 29456375
TI  - Assessment of Queries Received by the Drug Information Center at King Saud
      Medical City.
AB  - Background: The complexity of drug therapies has increased the need to evaluate
      the drug information scientifically. In this regard, the aim of drug information
      centers (DICs) is to promote rational use of drugs in a health-care setting. DI
      pharmacists play a vital role in providing the necessary and reliable information
      on drugs to promote the concept of rational drug use, eventually leading to a
      better patient outcome. The objective of the present study was to assess the drug
      related queries received by the DIC at the King Saud Medical City (KSMC) from
      health-care professionals working in a large tertiary care setting. Methods: A
      retrospective analysis was conducted from February 2016 to January 2017. Data
      were collected using the DI request form, available in both printed and
      electronic formats for use by the health-care professionals. Descriptive
      statistics were used to calculate frequencies and percentages. Data analysis was
      performed using the Statistical Package of the Social Sciences software, version
      16.0. Results: The current study received a total of 139 queries that were
      answered by the DIC pharmacists over a period of 1 year. The majority of queries
      were asked by pharmacists (61.2%), followed by physicians (23.7%) and nurses
      (10.10%). About half of the queries were related to the dosage and administration
      of the drugs. Lexicomp(r) acted as the common resource of information.
      Conclusion: DIC has been instrumental in the dissemination of drug-related
      information to health-care professionals since its inception in February 2016,
      resulting in the provision of quality health care to the patients. However, based
      on yearly queries, there still exists a need to increase the awareness of health
      care professionals about the DIC at KSMC, which will urge them to take drug
      consultation from DIC pharmacists and promote patient safety.

PMID- 29456374
TI  - Factors Affecting Primaquine Combination Treatment in Malaria Patients in
      Selangor, Malaysia.
AB  - Introduction: Primaquine is vital for the management of liver-stage Plasmodium
      vivax and Plasmodium ovale malaria. However, primaquine effectiveness is
      dependent on various factors and differs between populations. Therefore, this
      study was conducted to identify factors that affect the length of stay and
      relapse during primaquine combination treatment in malaria-infected patients in
      the local setting. Materials and Methods: A retrospective study on the use of
      primaquine combination among P. vivax and P. ovale infected patients in Selangor,
      Malaysia within a 5-year period from 2011 to 2015 was obtained from the National
      Malaria Case Registry, Malaysia. Data collected were patient characteristics
      (age, gender, nationality, glucose-6-phosphate dehydrogenase, pregnancy); disease
      characteristics (survival, past malaria infection, parasite type, presence of
      gametocyte, parasite count, week onset, severity, transmission type); and
      treatment characteristics (type of antimalarial, treatment completion). Outcome
      measures were length of stay and relapse during a 1-year follow-up. Results: A
      total of 635 patients were included in the study. Based on a multivariate
      logistic regression analysis, the significant predictors for length of stay were
      gender (P = 0.009) and indigenous transmission (P < 0.001). Male patients had a
      shorter length of stay than females by 0.868 days (P = 0.009), and indigenous
      transmission took 1.82 days more compared to nonindigenous transmission (P <
      0.001). Predictors for relapse were indigenous transmission of malaria (P =
      0.019), which was 15.83 times more likely to relapse than nonindigenous
      transmission (P < 0.01). Conclusions: This study reveals that the effectiveness
      of primaquine was clinically associated with gender and indigenous transmission.
      To that end, vigilant monitoring of primaquine use is required to reduce relapse
      and future transmission.

PMID- 29456376
TI  - Academic Stress and Prevalence of Stress-Related Self-Medication among
      Undergraduate Female Students of Health and Non-Health Cluster Colleges of a
      Public Sector University in Dammam, Saudi Arabia.
AB  - Objective: The objective was to report academic stress and prevalence of stress
      related self-medication among undergraduate female students of health and
      nonhealth cluster colleges at a public sector university in Dammam, Saudi Arabia.
      Materials and Methods: A 5-month cross-sectional survey was conducted in the
      university. The survey included the English version of 10-item Perceived Stress
      Scale (PSS) to report self-perceived stress. Student responses were analyzed by
      SPSS version 22 software. Results: The majority of students (85%) perceived
      examinations as a stressor. Most of the students (64%) had perceived moderate
      stress that increased as students progressed from preparatory year to 4th year.
      It declined in students of 5th and 6th year. The prevalence of stress related was
      reported at 39.58%. Highest prevalence of stress-induced self-medication was
      reported from College of Nursing (59.09%) and lowest (29.69%) from clinical
      pharmacy. Most common drug used to self-medicate during stress was caffeine
      (49.5%). The PSS score was significantly associated with colleges and study
      levels. Conclusion: Students studying in health cluster colleges reported high
      academic stress and self-medication practice. The major stressors identified were
      examination and course load. Student counseling sessions and counseling by
      pharmacists regarding self-care may help in the reduction of such stressors and
      may promote responsible self-medication. Self-evaluation and quality assurance
      process of curriculum may highlight areas for improvement in the courses. This
      may help in lowering academic stress among students.

PMID- 29456378
TI  - Utilization and Impact of Electronic and Print Media on the Patients' Health
      Status: Physicians' Perspectives.
AB  - Aims: Despite an increased popularity of print and electronic media applications,
      there is a paucity of data reflecting doctors' opinions regarding efficient
      utilization of these resources for the betterment of public health. Hence, this
      study aimed to investigate the perception of physicians toward the effect of
      electronic and print media on the health status of patients. Setting and Design:
      The current research is a cross-sectional study conducted from January 2015 to
      July 2015. The study population comprised physicians rendering their services in
      different hospitals of Karachi, Pakistan, selected by the nonprobability
      convenience sampling technique. In this study, 500 questionnaires were
      distributed through email or direct correspondence. Methods and Materials:
      Physicians' perception toward the impact of electronic and print media on the
      health status of patients was assessed with a 20-item questionnaire. Different
      demographic characteristics, such as age, gender, institution, position, and
      experience of respondents, were recorded. Quantitative data were analyzed with
      the use of Statistical Package for Social Sciences, version 20.0 (SPSS, Chicago,
      IL). The association of the demographic characteristics of the responses of
      physicians was determined by one-way ANOVA using 0.05 level of significance.
      Results: In this study, 254 physicians provided consent to show their responses
      for research purposes. A response rate of 50.8% was obtained. Nearly one-third of
      the respondents negated that patients get health benefit using electronic and
      print media. The majority did not consider electronic and print media as
      lifestyle-modifying factors. Physicians thought that patients particularly do not
      rely on mass media for acquiring health information and consider healthcare
      professionals as unswerving information resource. Conclusions: Mass media can be
      productive resources to augment awareness among patients, although physicians
      seem unconvinced about the extended usage of print/electronic media.

PMID- 29456377
TI  - Molecular Simulation Studies of 3,3'-Diindolylmethane as a Potent MicroRNA-21
      Antagonist.
AB  - Objective: In recent decades, the overexpression of microRNA-21 (miR-21) is found
      to be progressively linked with many diseases such as different types of cancers,
      cardiovascular diseases, and inflammation. Thereby, it has become an attractive
      target for pharmacological and genetic modulation in various diseases, and also
      for overcoming the resistance to chemotherapy in several cancers. Here, in this
      study, the role of molecular therapeutics of 3,3'-diindolylmethane (DIM) has been
      investigated for its ability to bind with the precursor miRNA as a target of miR
      21 (hsa-mir-21), which may alter the catalyzation process of dicer, a RNase III
      enzyme, involved in miRNA transcription. Methods: In this context, the present
      study describes the potential binding and the structure alteration properties of
      DIM to precursor miR-21 (pre-miR-21) through Molecular Docking and Molecular
      Dynamics simulation techniques. Results: As a corollary, DIM formed both non
      bonded and covalent interactions with the bases of pre-miR, while covalent
      interaction with guanine in the 6th position was found to be consensus in
      molecular dynamics simulation. Furthermore, the stability of both DIM and pre-miR
      21 was found to be inversely correlated to each other in binding condition.
      Conclusion: This result indicates that DIM can be used in target-based therapy
      and also as a lead for further development of potent small molecule miRNA
      antagonist.

PMID- 29456379
TI  - Assessment of Health-related Quality of Life Among Asthmatic Patients: The Need
      for Structured Pharmaceutical Care Delivery System in Pakistan.
AB  - Asthma is considered as one of the most common chronic diseases in the world. As
      a result of serious physical, social, and psychological complications, asthma can
      reduce health-related quality of life (HRQoL). The present study was designed to
      assess the HRQoL including physical health, general health perception, emotional
      health, psychological health, and social functioning of asthmatic patients in
      Pakistan. A descriptive cross-sectional study design was used. Setting was public
      and private healthcare facilities. SF-36 was self-administered to a sample of 382
      asthmatic patients. After data collection, data were clean coded and entered in
      SPSS version 21.0. Skewness test was performed and histograms with normal curves
      were used to check the normal distribution of data. Descriptive statistics
      comprising of frequency and percentages was calculated. The non-parametric tests
      including Mann-Whitney and Kruskal-Walis (P >= 0.05) were performed to find out
      the difference among different variables. The results of the current study
      highlighted a significant impact on several domains of HRQoL for asthmatic
      patients. Lowest scores for HRQoL were observed in the domain of general health
      (27.74 +/- 18.29) followed by domain of mental health (38.26 +/- 20.76) whereas
      highest scores were observed in the domain of social functioning (45.64 +/-
      25.89). The results of the study concluded that asthmatic patients in Pakistan
      had poor HRQoL. Well-structured pharmaceutical care delivery in the healthcare
      facilities can contribute toward better patient knowledge and management and can
      ultimately improve the HRQoL of asthma patients.

PMID- 29456380
TI  - Moxibustion (Artemisia Plant at Acupuncture Point) as Alternative Therapy in
      Hypertension: A Promising Approach.
AB  - Hypertension is a pathological condition in which the blood pressure is higher
      than under normal physiological conditions, i.e., 140/90 mmHg or higher. Blood
      pressure is measured as the force exerted by the blood pumped by the heart
      against the walls of arteries (aorta) and distributed throughout the body. Use of
      complementary and alternative medicine as a cure for hypertension is a common
      phenomenon because of the high risk of cardiovascular complications and kidney
      diseases caused by conventional Western medicine. It is reported that high blood
      pressure causes ~49% of myocardial infarction and 62% of strokes. Effective
      treatment of hypertension is restricted by adverse effects and cost of the
      medication. Moxibustion is the application of heat by burning a small bundle of
      tightly bound moxa, to targeted acupoint, and sometimes it is used along with
      acupuncture. Encouraging results have been reported on randomized trials
      indicating the efficacy of moxibustion. But more controlled clinical trials are
      required to further establish the potential efficacy of moxibustion approach in
      hypertension.

PMID- 29456381
TI  - Evaluation of Teaching Clinical Pharmacology of Antiarrhythmic Drugs to First
      Year MBBS Students Through Worksheet-Based Small-Group Discussion.
AB  - Cardiac arrhythmias are a major cause of morbidity and mortality across the
      world. Learning the science behind the use of antiarrhythmic drugs is essential
      for all medical graduates. However, many antiarrhythmic drugs are available, and
      most of them have complex pharmacodynamic and pharmacokinetic profiles. We tried
      to improvise our teaching by conducting interactive, worksheet-based, small-group
      discussion on antiarrhythmic drugs with preclinical students of School of
      Medicine, Taylor's University, Malaysia. This survey was conducted to analyze the
      outcomes of worksheet-based, small-group discussion.

PMID- 29456382
TI  - Deflazacort-induced Acneiform Eruptions.
AB  - A 38-year-old male suffering from a low backache since 3 months was diagnosed as
      a case of L4-L5 disc prolapse after magnetic resonance imaging examination. He
      was treated with tolperisone, aceclofenac, and paracetamol in these drugs
      deflazacort added later. From the 2nd day of an addition of deflazacort in the
      therapy, sharply marginated, infiltrative, and erythematous skin eruptions with
      discrete itching sensations were seen. It was diagnosed as deflazacort-induced
      acneiform eruption and treated with doxycycline for 2 months which led to the
      disappearance of acneiform eruptions.

PMID- 29456383
TI  - Rediscovering the Drug Discovery with Natural Products as Therapeutic Tools.

PMID- 29456384
TI  - Tea Polyphenols and Prevention of Epigenetic Aberrations in Cancer.
AB  - Tea polyphenols are secondary metabolites of tea plants and are well known for
      beneficial health effects. They can protect from a variety of illnesses including
      cancers. Tea polyphenols can prevent cancer by modulating epigenetic aberrations
      taking place in DNA methylation, histone modifications, and micro-RNAs. By
      altering these epimutations, they regulate chromatin dynamics and expression of
      genes those induce or suppress cancer formation. However, majority of the studies
      in existing literature are carried out for green tea polyphenols rather than
      black tea polyphenols despite the fact that black tea is the most commonly
      consumed form of tea (78%) followed by green tea (20%) and other forms of tea.
      Research findings indicate that tea polyphenols may be potential source from
      which drugs with less side effects and affordable price can be developed.

PMID- 29456385
TI  - DNA Damage Protecting Activity and Antioxidant Potential of Launaea taraxacifolia
      Leaves Extract.
AB  - Background: The leaf extract of Launaea taraxacifolia commonly known as African
      Lettuce is used locally to treat dyslipidemia and liver diseases, which are
      associated with oxidative stress. Methanol extract from L. taraxacifolia leaves
      was tested for its antioxidant activity and its ability to protect DNA from
      oxidative damage. Materials and Methods: In vitro antioxidant potential of the
      leaf extract was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric
      oxide (NO), and hydroxyl (OH) radical scavenging assays. Ferric reducing power,
      total antioxidant capacity (TAC), metal chelating, and anti-lipid peroxidation
      ability of the extract were also examined using gallic acid, ascorbic acid,
      citric acid, and ethylenediaminetetraacetic acid as standards. Results: L.
      taraxacifolia leaves extract showed antioxidant activity with IC50 values of
      16.18 MUg/ml (DPPH), 123.3 MUg/ml (NO), 128.2 MUg/ml (OH radical), 97.94 MUg/ml
      (metal chelating), 80.28 MUg/ml (TAC), and 23 MUg/ml (anti-lipid peroxidation
      activity). L. taraxacifolia leaves extract exhibited a strong capability for DNA
      damage protection at 20 mg/ml concentration. Conclusion: These findings suggest
      that the methanolic leaf extract of L. taraxacifolia could be used as a natural
      antioxidant and also as a preventive therapy against diseases such as
      arteriosclerosis associated with DNA damage.

PMID- 29456387
TI  - Clinico-epidemiological Profile of Pediatric Rheumatology Disorders in Eastern
      India.
AB  - Background: Data on rheumatological disorders in children from developing
      countries like India are scarce. Hence, this study aimed to understand the
      clinical and epidemiological profile of rheumatological disorders in children as
      this can help organize comprehensive evidence-based health care services.
      Methodology: A retrospective hospital-based study was designed in pediatric
      rheumatology clinic of the All India Institute of Medical Sciences, Patna, India,
      from January 2015 to December 2016. Clinical and laboratory findings and response
      to therapy of all children with rheumatological disorders were evaluated.
      Results: A total of 60 children with various rheumatological disorders were
      included in the study. Juvenile idiopathic arthritis (JIA) was the most common
      pediatric rheumatology disorder observed, and polyarticular JIA was the
      predominate subtype observed in our patients. The mean age of disease onset was
      9.1 +/- 3.6 years (age range: 1-16 years). Methotrexate was the most common
      disease modifying antirheumatic drug used. None of the children received newer
      biological agents due to financial constraints. The use of alternative medicine
      was observed in 10% of cases. Conclusion: The clinical and epidemiological
      profile of children with rheumatological disorders in our patient group was
      different from the European countries and Western world. There is a need for
      introspecting the lack of using biological agents and its potential impact in
      managing JIA in our patient group.

PMID- 29456386
TI  - Perception of Patient Safety Culture among Health-care Providers in a Tertiary
      Care Hospital, South India.
AB  - Introduction: Patient safety is a global concern and is the most important
      domains of health-care quality. Medical error is a major patient safety concern,
      causing increase in health-care cost due to mortality, morbidity, or prolonged
      hospital stay. Aim: The aim of the study was to assess the perceptions on patient
      safety culture among health-care providers (HCPs) at a public sector tertiary
      care hospital in South India. Settings and Design: A hospital-based cross
      sectional study was conducted 1 year after patient safety initiatives were
      implemented. Materials and Methods: Participants were selected through
      proportionate stratified random sampling. The Hospital Survey on Patient Safety
      Culture was used to assess perception of patient safety culture. Responses were
      collected on a Likert scale and were categorized into four types as negative,
      neutral, positive response, and nonresponse. Statistical Analysis Used: The data
      were entered in EpiData Version 3.1 and analyzed using SPSS Version 17.
      "Composite positive response rate" for the various dimensions was calculated.
      Results: The overall response rate in the study was 91.6%. Average composite
      positive response rate was 58%, and it varied among different cadres of HCPs
      ranged from 53% to 61%. The dimensions "teamwork within the unit,"
      "organizational learning and continuous improvement," and "supervisor or officer
      in-charge expectations" showed highest positive responses (80.1%, 77.8%, and
      71.5%, respectively). Conclusions: This survey conducted after implementation of
      patient safety drive showed that, in many dimensions, the patient safety culture
      has taken roots. The dimensions such as "hand-off and transitions," "frequency of
      events reporting," and "communication openness" had scope for further
      improvement.

PMID- 29456388
TI  - Analgesic Properties of Nigella Sativa and Eucheuma Cottonii Extracts.
AB  - Background: This study investigates the analgesic properties of the aqueous
      extracts of Nigella sativa and Eucheuma cottonii in mice. The analgesic
      properties of both extracts were evaluated in an experimental model of acetic
      acid-induced writhing test. Materials and Methods: The mice were divided into
      four different groups and received the test extracts and the standard drug
      (aspirin) for 14 days via force-feeding. On day 15, the mice were injected with
      5% acetic acid, and the number of abdominal constriction and elongation of hind
      limb (writhes) were counted for 20 min. Results: The numbers of writhes were
      counted starting after 5 min of the acetic acid injection. The N. sativa extracts
      significantly reduced the number of writhes as compared to the control group.
      Both of the extracts revealed a comparable result as referred to the aspirin
      effects in the mice. Conclusions: These findings indicate that N. sativa and E.
      cottonii may possess protective active constituent that is effective in reducing
      the sensation of pain in mice.

PMID- 29456389
TI  - Assessment of Quality of Prescription Writing among Dental and Medical Students
      and Practitioners in Kerala.
AB  - Background: The medical prescription is a valid and legal document. Prescriptions
      can also be used as a measure of the quality of medical education, observance of
      the laws and regulations, and sociocultural beliefs. Aims: To assess the quality
      of prescription written by dental and medical students and practitioners.
      Settings and Design: A cross-sectional study was conducted in three dental and
      two medical colleges in Kerala covering 345 participants (dental - 235 and
      medical - 110). Materials and Methods: Simulation exercise was conducted for
      drafting a model prescription based on a given clinical condition. The variables
      were identified based on the model prescription format by the Medical Council of
      India and were classified into four domains. Points were assigned for each
      variable. Statistical Analysis Used: Analysis was performed using descriptive
      statistics and Mann-Whitney U-test. Results and Conclusion: The total scores were
      found to be higher among dental fraternity (10.93 +/- 2.88) to medical (10.81 +/-
      2.55). The medical house surgeons and postgraduates fared better in the doctor
      identification domain. Among the dental professionals, there was a significant
      difference among the undergraduates (mean score = 1.91) and postgraduates (mean
      score = 1.60) in the doctor identification domain. However, among the medical
      professionals, in the patient identification domain, house surgeons had a
      significantly higher score compared to postgraduates. There were no significant
      differences in quality of prescription writing among medical and dental
      professionals.

PMID- 29456390
TI  - Evaluation of Clinical and Magnetic Resonance Imaging Profile of Pituitary
      Macroadenoma: A Prospective Study.
AB  - Background: Pituitary macroadenoma is a common tumor of middle-aged people.
      Magnetic resonance imaging (MRI) is the investigation of choice for its
      evaluation. Various parameters regarding the extent, consistency, and contrast
      uptake can be studied and a noninvasive diagnosis is possible. Aims and
      Objectives: To study the MRI features and extent of pituitary macroadenomas.
      Materials and Methods: We studied clinical and MRI features of 33 patients of all
      age groups and both sexes with pituitary macroadenomas who presented to Dayanand
      Medical College and Hospital, Ludhiana from January 2014 to June 2015. MRI was
      carried out on MAGNETOM Avanto 18 Channel 1.5 Tesla Machine by Seimens India Ltd.
      The dedicated sellar protocol consisted of sagittal and coronal T1-weighted image
      (TI-WI) and T2-WI without intravenous contrast using thin slices (3 mm) and a
      field of view of <200 mm. Results: On analysis of the 33 cases, we observed that
      patients of pituitary macroadenoma showed an almost equal sex incidence and
      average age group of 50-60 years. The common presenting complaints were headache
      and decreased vision. Superior and inferior extent of the lesion was beyond the
      defined boundaries of sella in most cases, but the lateral extent was limited,
      resulting in characteristic "snowman-like" appearance. The imaging
      characteristics showed solid to predominantly solid consistency, appearing mostly
      heterogeneously hyperintense on T2-WI, and hypo to isointense on T1-WI with
      intense postcontrast enhancement. Hemorrhage is less common. Pituitary apoplexy
      is rare and can result in spontaneous resolution. Conclusions: We conclude that
      the knowledge of clinical and imaging profile of pituitary macroadenoma can help
      the radiologists to diagnose these sellar lesions, and hence their therapeutic
      approach can be defined timely.

PMID- 29456392
TI  - Chest X-Ray Findings Comparison between Multi-drug-resistant Tuberculosis and
      Drug-sensitive Tuberculosis.
AB  - Background: Imaging has a big role in tuberculosis (TB) diagnosis and chest X-ray
      is preferable because it is available in primary health care and can point out
      the location, area, and morphology of lesions, such as cavity, consolidation,
      pleural effusions, and fibrosis. We aimed to compare the chest X-ray findings in
      multi-drug resistant TB (MDR-TB) and in drug-sensitive TB (DS-TB) cases. Methods:
      This is a retrospective cross-sectional study which compares chest X-ray findings
      of two groups of patients, involving 183 DS-TB patients and 183 MDR-TB patients.
      Radiologic findings that we analyzed were infiltrate, consolidation, cavity,
      ground glass opacity, fibrosis, bronchiectasis, calcification, node, atelectasis,
      bullae, emphysema, and other nonlung parenchymal findings. Results: MDR-TB group
      have 177 (96%) patients with large lesions, 6 (4%) with medium lesions, and no
      small lesions. DS-TB group have 55 (30%) patients with small lesions, 78 (43%)
      with medium lesions, and 50 (27%) with large lesions. Active TB lesions in the
      forms of infiltrate and ground-glass opacity were more dominant in DS-TB group,
      whereas consolidation, cavity, fibrosis, bronchiectasis, calcification, node,
      atelectasis, bullae, emphysema, and other nonlung parenchymal findings, were more
      dominant in MDR-TB. Conclusions: There were significant differences in chest X
      ray findings between MDR-TB and DS-TB in terms of lesion size and morphology.
      Recognition of chest X-ray findings could help the physician to differentiate
      patient with suspected MDR-TB.

PMID- 29456391
TI  - The Use of Thromboelastography to Measure the Influence Inclusion of a Local
      Anesthetic Agent has on the Mechanical and Kinetic Properties of Fibrin.
AB  - Context: Delivery of slow-release local anesthesia has considerable potential for
      postoperative analgesia. Fibrin gel has shown huge potential for drug delivery,
      but has not been fully investigated for the delivery of local anesthetics nor has
      whether incorporation of anesthetic drugs into fibrin alters its mechanical
      properties. Aims: This study aimed to evaluate the effects of bupivacaine
      inclusion on the mechanical and kinetic properties of fibrin as measured by
      thromboelastography (TEG). Materials and Methods: Serial dilutions of fibrinogen
      with thrombin were tested with TEG to identify the optimal concentrations to give
      reproducible results. Following this, fibrinogen samples diluted with bupivacaine
      0.5% in place of normal saline (also 1:20 dilution) were added to thrombin to
      assess what influence this had on clot strength and kinetics as measured by TEG
      values (with R, K, and alpha angle relating to clot kinetics and MA and G (or
      shear elastic modulus strength) relating to clot strength). Results: The mean
      values yielded for R were higher and lower for alpha angle, suggesting that the
      inclusion of bupivacaine produced a fibrin clot at a slower rate. The values for
      MA and G were both lower when bupivacaine was included, suggesting inclusion of
      the local anaesthetic also resulted in a fibrin clot of inferior strength. These
      results were not statistically significant. Conclusion: Although TEG failed to
      consistently measure these properties, the results suggest that inclusion of
      local anesthetic affects the clotting process of fibrin, potentially interfering
      with its ability to function as a sealant, adhesive, or hemostat.

PMID- 29456393
TI  - In vitro H+/K+-ATPase Inhibition, Antiradical Effects of a Flavonoid-rich
      Fraction of Dissotis rotundifolia, and In silico PASS Prediction of its Isolated
      Compounds.
AB  - Background: Dissotis rotundifolia, commonly referred to as pink lady, has several
      medicinal uses including peptic ulcer. This study investigated the inhibitory
      effects of D. rotundifolia extract on H+/K+-ATPase and also assessed its
      antiradical activity. In silico study of some isolated compounds of this plant
      was also carried out to affirm the suspected binding properties of extract to
      H+/K+-ATPase enzyme. Materials and Methods: D. rotundifolia whole plant extract
      was obtained after extraction process and then assessed for its ability to
      scavenge free radicals in four in vitro test models. Its ability to inhibit the
      activity of H+/K+-ATPase enzyme was also evaluated. Molecular docking was carried
      out on phytoconstituents, namely, vitexin, isovitexin, orientin, and isoorientin
      reported to be present in the whole plant extract. Results: Data obtained
      indicated that D. rotundifolia extract (DRE) exhibits strong antioxidant
      activity. DRE also showed inhibitory effects on H+/K+-ATPase enzyme activity.
      Docking studies affirmed the in vitro binding effect of the extract to H+/K+
      ATPase. Conclusion: These findings suggest that the plant extract possess
      antioxidant and antipeptic ulcer activity.

PMID- 29456394
TI  - Assessment of Vitamin D in Rheumatoid Arthritis and Its Correlation with Disease
      Activity.
AB  - Background: Vitamin D is believed to have an immunomodulatory and anti
      inflammatory action, and its deficiency has been linked with several autoimmune
      disorders, including rheumatoid arthritis (RA). The relationship between the
      severity of RA and serum levels of Vitamin D is a subject of immense interest and
      therapeutic implications. Materials and Methods: This was a prospective,
      comparative study conducted on 100 participants, 50 cases of RA and 50 healthy
      controls, all in the age group of 18-75 years. Serum Vitamin D levels were
      measured and compared in cases and controls. Vitamin D levels in RA patients were
      also assessed in different stages of disease activity to assess the correlation
      between the two. Results: Eighty-four percent patients of RA were Vitamin D
      deficient versus only 34% of controls. The serum Vitamin D levels were also
      significantly lower in the RA patients (mean value of 21.05 +/- 10.02 ng/ml), as
      compared to the controls (mean value of 32.87 +/- 14.16 ng/ml). There was a
      significant inverse correlation between serum Vitamin D levels and RA disease
      activity. The mean serum Vitamin D levels were 35.28 +/- 9.0 ng/ml, 33.80 +/- 4.1
      ng/ml, 22.47 +/- 6.18 ng/ml, and 14.21 +/- 6.97 ng/ml in the remission, low
      disease activity, moderate disease activity, and high disease activity groups,
      respectively. Conclusions: Vitamin D deficiency is more common in RA patients and
      may be one of the causes leading to development or worsening of the disease.

PMID- 29456395
TI  - Incidence and Pattern of Mandible Fractures in the Madinah Region: A
      Retrospective Study.
AB  - Objectives: The objective of the study is to study the incidence and pattern of
      mandible fractures in the holy city of Madinah in the Kingdom of Saudi Arabia
      over a retrospective period of 3 years from 2013 (1434H) to 2016 (1436H) and to
      compare the results with those from other regions of Saudi Arabia and elsewhere.
      Materials and Methods: Relevant data of patients admitted to the King Fahad
      Hospital, Madinah with a fracture of the mandible during the study were collected
      from their medical records and radiographs. The age, gender, etiology, role of
      the patient, site, and number of fractures in the patients were evaluated. The
      data were analyzed by standard statistical methods. Results: A total of 197
      patients with fracture of the mandible were admitted in the period of the study
      by the Oral Maxillofacial Surgery Department, King Fahad Hospital, Madinah. There
      were 165 male and 32 female patients. The ages ranged from 3 to 86 years with a
      mean of 24 years. A total of 260 fractures of Mandible were documented. The
      largest number (113) of patients was found in the age group between 16 and 30
      years. Trauma caused by motor vehicle road traffic accidents (RTAs) was the main
      etiology of the fractures followed by falls and assault. The majority of the
      patients were in the role of vehicle drivers. The condylar anatomical site of
      mandible was most frequently affected and constituted the largest number (103) of
      fractures followed by the angle (51), parasymphysis (45), and then by the body
      (23) of the mandible. Dentoalveolar fractures were present in 22 cases. Very less
      number of coronoid fractures (7), followed by those of the ramus (5), and least
      number at the symphysis (4) of the mandible were found. Conclusion: RTA was the
      most common etiology for trauma and fracture of the mandible. The males
      outnumbered the female patients, the largest number of patients with trauma and
      mandible fracture was found in the age group between 16 and 30 years and
      frequency of condylar fractures was higher.

PMID- 29456396
TI  - Gingival Tissue Response Following Placement of a Light Cure Dressing and a Non
      eugenol Dressing after Periodontal Flap Procedure: A Comparative Clinical Study.
AB  - Aim: The aim was to compare the gingival tissue response following placement of a
      light cure dressing (Barricaid(r)) and a non-eugenol periodontal dressing (Coe
      PakTM) after periodontal flap procedure. This was carried out by evaluating
      plaque deposition underneath both the dressings, healing response and the patient
      preference for each. Materials and Methods: A total of 12 patients with chronic
      generalized periodontitis requiring surgery in at least two different quadrants
      were enrolled for this split-mouth study. After periodontal flap surgery, Coe
      PakTM was placed in the quadrant assigned to Group I and Barricaid(r) was placed
      in the other quadrant assigned to Group II. Clinical parameters were recorded on
      day 7 and day 14. Patient comfort and pain levels were also evaluated by a
      questionnaire. Results: There were no statistically significant differences in
      wound healing and the clinical gingival parameters between two groups. The only
      significant difference was found in the plaque attached underneath the dressing,
      with Coe-PakTM showing greater plaque accumulation than Barricaid(r). Seventy
      five (75) % of the patients preferred Barricaid(r) over Coe-PakTM, based on its
      appearance and taste. Conclusion: The non-eugenol dressing seemed to retain more
      plaque on its undersurface than light-cure dressing. However, this did not have
      much influence on the healing outcome and clinical gingival parameters, which
      were optimal and comparable in both groups. The greater number of patients showed
      a preference for light cure dressing, based on its superior esthetics and taste.

PMID- 29456397
TI  - Periodontal Flap Surgery along with Vestibular Deepening with Diode Laser to
      Increase Attached Gingiva in Lower Anterior Teeth: A Prospective Clinical Study.
AB  - Background: Chronic periodontitis in lower anterior teeth results in rapidly
      progressive gingival recession (GR), loss of alveolar bone, decreased vestibular
      depth (VD) with consequential tooth mobility, and tooth loss. Treatment option
      for such cases in this esthetically important area of the oral cavity includes
      extraction followed by implants for which sufficient bone height and mucogingival
      complex are a prerequisite. Henceforth, an attempt was made to prolong the life
      of lower anterior teeth and postpone the need for implants by the treatment of
      chronic periodontitis with periodontal flap surgery followed by vestibular
      deepening in single surgical procedure. Materials and Methods: In this clinical,
      prospective study, conventional periodontal flap surgery was done on 74 sites in
      lower anterior teeth in 16 patients with attachment loss >5 mm due to chronic
      periodontitis. Vestibular deepening with diode laser at (wavelength - 810 nm,
      output power: 0.5-7 W, continuous wave, contact mode) was done after suturing the
      flap. All the clinical parameters: GR, pocket depth (PD), clinical attachment
      loss (CAL), width of keratinized gingiva, width of attached gingiva, and VD were
      assessed preoperatively after Phase I therapy and 6 months postoperatively.
      Results: At all the 74 sites, there was highly significant gain in attached
      gingiva, keratinized gingiva, and VD (P <= 0.001). Highly significant reduction
      in PD (P <= 00.001), significant reduction in attachment loss (P <= 0.01) but no
      significant reduction in GR (P = 0.897) was observed. Conclusions: The
      combination of periodontal flap surgery with vestibular deepening with diode
      laser may be a suitable cost-effective treatment option to prolong the life of
      periodontally involved lower anterior teeth. The surgical technique can postpone
      the need for extraction of teeth along with all the intangible benefits of
      periodontal therapy.

PMID- 29456398
TI  - Urinary Cotinine Level in Indonesian Children Exposed to Domestic Cigarette
      Smoke.
AB  - Background: Cotinine is a major metabolite of nicotine, and its urinary level is
      an indicator of exposure to cigarette smoke. The present study was aimed at
      identifying the urinary cotinine level in Indonesian children who were exposed
      and not exposed to domestic cigarette smoke. Methods: The study was a cross
      sectional study in elementary school-aged children who had not smoked. The
      subjects were categorized into an exposed group and unexposed group based on
      their exposure status. Data were obtained from a questionnaire and random urinary
      samples measured using enzyme-linked immunosorbent assay. Results: There were a
      total of 128 subjects, including 64 children in the exposed group and 64 children
      in the unexposed group. The median level of cotinine in all subjects was 17.95
      ng/ml (with a range of 0.1-158.3 ng/ml). The urinary cotinine level in the
      exposed group was higher than the unexposed group (median: 30.1 ng/ml vs. 8.45
      ng/ml; P < 0.000). There was a correlation between urinary cotinine levels in
      children exposed to cigarette smoke and the number of cigarettes smoked by the
      smokers at home (P < 0.05). The optimal cut-off points of urinary cotinine levels
      in children, which was utilized to evaluate cigarette smoke exposure, was 17.95
      ng/ml (81% sensitivity; 81% specificity; P < 0.000). Conclusion: The urinary
      cotinine level in children exposed to cigarette smoke is higher than children who
      are not exposed to domestic cigarette smoke. The urinary cotinine level can be
      used as a noninvasive marker to evaluate cigarette smoke exposure in children.

PMID- 29456399
TI  - Preprocedural Anxiety and Pain Perception Following Root Surface Debridement in
      Chronic Periodontitis Patients.
AB  - Background: The aim of this study was to evaluate and compare preprocedural
      dental anxiety levels and postprocedural pain perception in chronic periodontitis
      patients during conventional-staged root surface debridement (RSD) and single
      stage RSD. Materials and Methods: Thirty-seven adult generalized chronic
      periodontitis patients requiring RSD were recruited in this study. Preprocedural
      anxiety levels were assessed using a self-reported questionnaire and
      postprocedural pain perceptions were assessed using 0-10 cm visual analog scale.
      The subject population was divided into two groups: staged RSD (n = 18) and
      single-stage RSD (n = 19). Staged RSD patients visited four times as opposed to
      single-stage RSD patients. Data were subjected to Pearson Chi-square test, Mann
      Whitney U-test, and Spearman's rank correlation. Results: There was no
      statistically significant difference in dental anxiety levels or pain perceptions
      in both the groups. Within Group 1, there was statistical significant difference
      in dental anxiety levels between visit 4 and visit 3 (P = 0.037) and pain
      perception between visit 3 and visit 1 (P = 0.005), visit 4 and visit 1 (P =
      0.002), and visit 4 and visit 2 (0.04) was statistically significant. There was a
      positive correlation of anxiety questionnaire (Q1-Q4) to the pain score in Group
      1 which was statistically significant and in single-stage RSD. Conclusion:
      Conventional quadrant-wise RSD tends to cognitively condition the anxiety
      experience thus influencing pain experience.

PMID- 29456400
TI  - Unilateral Transient Watershed Cerebral Infarct in a 6-Year-Old Girl with
      Frequently Relapsing Nephrotic Syndrome.
AB  - Nephrotic syndrome is a prothrombotic state with predisposition to venous sinus
      thrombosis and arterial vascular stroke. Watershed infarcts in junction of
      arterial territory develop in hypotensive hypovolemic state. These border zone
      infarcts are usually bilateral in the absence of unilateral arterial stenosis or
      microembolism. We report a 6-year-girl of frequently relapsing nephrotic syndrome
      who developed sudden onset hemiparesis with aphasia. Magnetic resonance (MR)
      imaging brain revealed unilateral watershed infarct in territory between the
      major cerebral arterial vessels with evidence of restricted diffusion and normal
      vessel anatomy on MR angiography. This could possibly reflect asymmetric variant
      of posterior reversible encephalopathy syndrome that resolved with remission on
      steroids.

PMID- 29456401
TI  - Management of Complicated Crown Fracture by Reattachment Using Fiber Post:
      Minimal Intervention Approach.
AB  - Anterior crown fractures are a common form of traumatic dental injuries that
      mainly affect the maxillary incisors, especially in children and adolescents.
      Complicated crown fractures although less common, pose a challenge to the
      clinician. The main objective while treating such cases is successful pain
      management and immediate restoration of function, esthetics and phonetics. Since
      the development of the adhesive dentistry, the patient's own fragment can be used
      to restore the fractured tooth. Reattachment of fractured tooth fragments offers
      a viable restorative alternative. The procedure provides good and long-lasting
      esthetics, because the original morphology, color, and surface texture are
      preserved. This article reports management of complicated crown fracture in a
      young adult and a middle-aged adult that were successfully treated by
      reattachment technique. The teeth were endodontically treated followed by
      esthetic reattachment of the fractured fragment using the glass fiber post. To
      improve the adhesion between fractured and remaining fragment, circumferential
      beveling and internal groove placement were done.

PMID- 29456402
TI  - Hemisection as a Conservative Management of Grossly Carious Permanent Mandibular
      First Molar.
AB  - Hemisection of a molar denotes removal or separation of a root along with its
      accompanying part of crown. It is a suitable treatment option when the caries,
      resorption, perforation, or periodontal damage is restricted to one root while
      the other root is relatively healthy. Hemisection of the affected tooth helps to
      retain the tooth structure, surrounding alveolar bone, and may also facilitate
      the placement of fixed prosthesis. This case report describes the hemisection as
      a successful treatment method to save a grossly carious mandibular first molar
      with periodontal and periapical involvement. Hemisection and prosthetic
      rehabilitation yielded a satisfactory result. With careful treatment planning and
      precise surgical management, undesirable consequences of tooth loss were
      prevented.

PMID- 29456403
TI  - Severe Abdominal Complaints after Technical Successful Endovascular Treatment of
      Chronic Splanchnic Ischemia.
AB  - Reperfusion syndrome (RS) after revascularization of an arterial occlusion of the
      lower leg is a well-known complication. RS after splanchnic revascularization,
      however, is an infrequent and less-known phenomenon. We present a patient with
      persisting abdominal complaints after revascularization of the celiac trunk and
      superior mesenteric artery suggesting reocclusion. Although computed tomography
      angiography showed patent splanchnic arteries, an impressive hyperperfusion state
      of liver and spleen was visualized. Complaints diminished steadily with
      conservative therapy, but RS can cause severe complications such as liver failure
      and multiple organ failure. Ignorance of RS might interfere with adequate
      treatment and can contribute to a high in-hospital mortality rate.

PMID- 29456404
TI  - "Thanatophobia": Physician's Perspective of Dealing with Patients with Fear of
      Death.

PMID- 29456405
TI  - Role of PTPN2/22 polymorphisms in pathophysiology of Crohn's disease.
AB  - AIM: To establish the relationship of protein tyrosine phosphatase non-receptor
      type 2 and 22 (PTPN2/22) polymorphisms and mycobacterial infections in Crohn's
      disease (CD). METHODS: All 133 subjects' blood samples were genotyped for nine
      single nucleotide polymorphisms (SNPs) in PTPN2/22 using TaqManTM genotyping,
      while the effect of the SNPs on PTPN2/22 and IFN-gamma gene expression was
      determined using RT-PCR. Detection of Mycobacterium avium subspecies
      paratuberculosis (MAP) IS900 gene was done by nPCR after DNA extraction from the
      isolated leukocytes of each subjects' blood samples. T-cells isolated from the
      patient samples were tested for response to phytohematoagglutonin (PHA) mitogen
      or mycobacterial antigens by BrdU proliferation assays for T-cell activity.
      RESULTS: Out of the nine SNPs examined, subjects with either heterozygous
      (TC)/minor (CC) alleles in PTPN2:rs478582 occurred in 83% of CD subjects compared
      to 61% healthy controls (P-values < 0.05; OR = 3.03). Subjects with either
      heterozygous (GA)/minor (AA) alleles in PTPN22:rs2476601 occurred in 16% of CD
      compared to 6% healthy controls (OR = 2.7). Gene expression in PTPN2/22 in CD
      subjects was significantly decreased by 2 folds compared to healthy controls (P
      values < 0.05). IFN-gamma expression levels were found to be significantly
      increased by approxiately 2 folds in subjects when either heterozygous or minor
      alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 were found (P-values < 0.05).
      MAP DNA was detected in 61% of CD compared to only 8% of healthy controls (P
      values < 0.05, OR = 17.52), where subjects with either heterozygous or minor
      alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 had more MAPbacteremia presence
      than subjects without SNPs did. The average T-cell proliferation in CD treated
      with PHA or mycobacteria antigens was, respectively, 1.3 folds and 1.5 folds
      higher than healthy controls without any significant SNP. CONCLUSION: The data
      suggests that SNPs in PTPN2/22 affect the negative regulation of the immune
      response in CD patients, thus leading to an increase in inflammation/apoptosis
      and susceptibility of mycobacteria.

PMID- 29456406
TI  - Health-related quality of life, anxiety, depression and impulsivity in patients
      with advanced gastroenteropancreatic neuroendocrine tumours.
AB  - AIM: To compare health-related quality of life (HRQoL), anxiety, depression, and
      impulsivity scores in patients with and without carcinoid syndrome (CS), and
      correlated them with serum 5-hydroxyindoleacetic acid (5-HIAA) levels. METHODS:
      Patients with advanced gastroenteropancreatic neuroendocrine tumours (GEPNET),
      with and without CS completed HRQoL QLQ-C30 and QLQ-GI.NET21, Hospital Anxiety
      and Depression Scale (HADS) and Barratt Impulsivity Scale (BIS) questionnaires.
      Two-sample Wilcoxon test was applied to assess differences in serum 5-HIAA
      levels, two-sample Mann-Whitney U test for HRQoL and BIS, and proportion test for
      HADS, between those with and without CS. RESULTS: Fifty patients were included;
      25 each with and without CS. Median 5-HIAA in patients with and without CS was
      367nmol/L and 86nmol/L, respectively (P = 0.003). Scores related to endocrine
      symptoms were significantly higher amongst patients with CS (P = 0.04) and scores
      for disease-related worries approached significance in the group without CS, but
      no other statistically-significant differences were reported between patients
      with and without CS in responses on QLQ-C30 or QLQ-GI.NET21. Fifteen patients
      (26%) scored >= 8/21 on anxiety scale, and 6 (12%) scored >= 8/21 on depression
      scale. There was no difference in median 5-HIAA between those scoring < or >=
      8/21 on anxiety scale (P = 0.53). There were no statistically significant
      differences between groups in first or second-order factors (BIS) or total sum (P
      = 0.23). CONCLUSION: Excepting endocrine symptoms, there were no significant
      differences in HRQoL, anxiety, depression or impulsivity between patients with
      advanced GEPNET, with or without CS. Over one quarter of patients had high
      anxiety scores, unrelated to peripheral serotonin metabolism.

PMID- 29456407
TI  - Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651
      polymorphism in a Spanish population.
AB  - AIM: To determine the variability/conservation of the domain of hepatitis B virus
      (HBV) preS1 region that interacts with sodium-taurocholate cotransporting
      polypeptide (hereafter, NTCP-interacting domain) and the prevalence of the
      rs2296651 polymorphism (S267F, NTCP variant) in a Spanish population. METHODS:
      Serum samples from 246 individuals were included and divided into 3 groups:
      patients with chronic HBV infection (CHB) (n = 41, 73% Caucasians), patients with
      resolved HBV infection (n = 100, 100% Caucasians) and an HBV-uninfected control
      group (n = 105, 100% Caucasians). Variability/conservation of the amino acid (aa)
      sequences of the NTCP-interacting domain, (aa 2-48 in viral genotype D) and a
      highly conserved preS1 domain associated with virion morphogenesis (aa 92-103 in
      viral genotype D) were analyzed by next-generation sequencing and compared in 18
      CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was
      determined in all individuals in all 3 groups using an in-house real-time PCR
      melting curve analysis. RESULTS: The HBV preS1 NTCP-interacting domain showed a
      high degree of conservation among the examined viral genomes especially between
      aa 9 and 21 (in the genotype D consensus sequence). As compared with the virion
      morphogenesis domain, the NTCP-interacting domain had a smaller proportion of HBV
      genotype-unrelated changes comprising > 1% of the quasispecies (25.5% vs 31.8%),
      but a larger proportion of genotype-associated viral polymorphisms (34% vs
      27.3%), according to consensus sequences from GenBank patterns of HBV genotypes A
      to H. Variation/conservation in both domains depended on viral genotype, with
      genotype C being the most highly conserved and genotype E the most variable
      (limited finding, only 2 genotype E included). Of note, proline residues were
      highly conserved in both domains, and serine residues showed changes only to
      threonine or tyrosine in the virion morphogenesis domain. The rs2296651
      polymorphism was not detected in any participant. CONCLUSION: In our CHB
      population, the NTCP-interacting domain was highly conserved, particularly the
      proline residues and essential amino acids related with the NTCP interaction, and
      the prevalence of rs2296651 was low/null.

PMID- 29456408
TI  - Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant
      irritable bowel syndrome.
AB  - AIM: To elucidate the mechanism of patchouli alcohol (PA) in treatment of rat
      models of diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: We
      studied the effects of PA on colonic spontaneous motility using its cumulative
      log concentration (3 * 10-7 mol/L to 1 * 10-4 mol/L). We then determined the
      responses of the proximal and distal colon segments of rats to the following
      stimuli: (1) carbachol (1 * 10-9 mol/L to 1 * 10-5 mol/L); (2) neurotransmitter
      antagonists including Nomega-nitro-L-arginine methyl ester hydrochloride (10
      MUmol/L) and (1R*, 2S*)-4-[2-Iodo-6-(methylamino)-9H-purin-9-yl]-2
      (phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester
      tetraammonium salt (1 MUmol/L); (3) agonist alpha,beta-methyleneadenosine 5'
      triphosphate trisodium salt (100 MUmol/L); and (4) single KCl doses (120 mmol/L).
      The effects of blockers against antagonist responses were also assessed by
      pretreatment with PA (100 MUmol/L) for 1 min. Electrical-field stimulation (40 V,
      2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic,
      noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of
      Kreb's solution was also determined. RESULTS: PA exerted a concentration
      dependent inhibitory effect on the spontaneous contraction of the colonic
      longitudinal smooth muscle, and the half maximal effective concentration (EC50)
      was 41.9 MUmol/L. In comparison with the KCl-treated IBS-D group, the contractile
      response (mg contractions) in the PA + KCl-treated IBS-D group (11.87 +/- 3.34)
      was significantly decreased in the peak tension (P < 0.01). Compared with CCh
      treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat
      colonic smooth muscle (EC50 = 0.94 MUmol/L) was significantly decreased by PA
      (EC50 = 37.43 MUmol/L) (P < 0.05). Lack of nitrergic neurotransmitter release in
      stress-induced IBS-D rats showed contraction effects on colonic smooth muscle.
      Pretreatment with PA resulted in inhibitory effect on L-NAME-induced (10 MUmol/L)
      contraction (P < 0.05). ATP might not be the main neurotransmitter involved in
      inhibitory effects of PA in the colonic relaxation of stress-induced IBS-D rats.
      CONCLUSION: PA application may serve as a new therapeutic approach for IBS-D.

PMID- 29456409
TI  - Recombinant expressed vasoactive intestinal peptide analogue ameliorates TNBS
      induced colitis in rats.
AB  - AIM: To investigate the modulatory effect of recombinant-expressed vasoactive
      intestinal peptide (VIP) analogue (rVIPa) on trinitrobenzene sulfonic acid (TNBS)
      induced colitis in rats. METHODS: Forty-eight rats were randomized into six
      groups: normal control group (Control), model control group (TNBS), ethanol
      treatment group (ETOH), and VIP treatment groups with different dosage
      (rVIPa1nmol, rVIPa2nmol, rVIPa4nmol). Diarrhea and bloody stool were observed.
      Colonic damage was evaluated histologically. The levels of tumor necrosis factor
      alpha (TNF-alpha), interleukin-10 (IL-10), myeloperoxidase (MPO) and endotoxin in
      colonic tissue and serum were determined by enzyme-linked immunosorbent assay
      (ELISA). The expression of occludin, ZO-1, Toll-like receptor 4 (TLR4), and
      nuclear factor-kappa B p65 (NF-kappaB p65), IkappaBalpha, and p-IkappaBalpha were
      detected by Western blot. RESULTS: Administration with 2 nmol rVIPa prevented
      TNBS-induced necrosis, hyperemia, swelling, inflammation, etc., pathologic
      changes observed in the inner surface of colon in experimental rats. Moreover,
      rVIPa significantly decreased colonic TNF-alpha level (P < 0.001), MPO activity
      (P < 0.001) and serum endotoxin level (P < 0.01), and remarkably increased
      colonic IL-10 content (P < 0.001) in rats with TNBS-induced colitis. Furthermore,
      compared to the TNBS-induced colitis group, 2 nmol rVIPa treatment up-regulated
      the levels of occludin (P < 0.05) and ZO-1 (P < 0.05), NF-kappaB p65 (P < 0.01)
      and IkappaBalpha (P < 0.001), and down-regulated the levels of TLR4. CONCLUSION:
      rVIPa ameliorates TNBS-induced colonic injury and inflammation and effectively
      protected the intestinal mucosal barrier function in rats. The mechanism may be
      related to TLR4/NF-kappaB-mediated signaling pathway. rVIPa could be used as a
      new alternative therapy for intestinal inflammatory disorders.

PMID- 29456410
TI  - Split-dose bowel preparation improves adequacy of bowel preparation and
      gastroenterologists' adherence to National Colorectal Cancer Screening and
      Surveillance Guidelines.
AB  - AIM: To quantify the impact of split-dose regimen on endoscopists' compliance
      with guideline recommendations for timing of repeat colonoscopy in patients with
      normal colonoscopy or 1-2 small polyps (< 10 mm). METHODS: A retrospective chart
      review of all endoscopy reports was undertaken in average-risk individuals > 50
      years old with a normal screening colonoscopy and 1-2 small polyps. Data were
      abstracted from two time periods, pre and post-split-dose bowel preparation
      institution. Main outcome measurements were recommendation for timing of repeat
      colonoscopy and bowel preparation quality. Bivariate analysis by chi2 tests and
      Student's t-tests were performed to assess differences between the two cohorts.
      Multivariable logistic regression was used with guideline consistent
      recommendations as the dependent variables and an indicator for 2011 cohort as
      the primary predictor. RESULTS: Four thousand two hundred and twenty-five
      patients were included in the study; 47.0% (1987) prior to the institution of
      split dose bowel preparation, and 53.0% (2238) after the institution of split
      dose bowel preparation. Overall, 82.2% (n = 3472) of the colonoscopies were
      compliant with guideline recommendations, with a small but significantly
      increased compliance rate in year 2011 (83.7%) compared to year 2009 (80.4%, P =
      0.005), corresponding to an unadjusted odds ratio of 1.25 (95%CI: 1.07-1.47; P =
      0.005). Colonoscopies with either "Adequate" or "Excellent" had increased from
      30.6% in year 2009 to 39.6% in year 2011 (P < 0.001). However, there was no
      significant difference in poor/inadequate category of bowel preparation as there
      was a mild increase from 4.6% in year 2009 to 5.1% in year 2011 (P = 0.50).
      CONCLUSION: Split-dose bowel regimen increases endoscopists' compliance to
      guidelines in average-risk patients with normal colonoscopy or 1-2 small polyps.

PMID- 29456411
TI  - Clinical utility of hepatitis B surface antigen kinetics in treatment-naive
      chronic hepatitis B patients during long-term entecavir therapy.
AB  - AIM: To investigate the utility of hepatitis B surface antigen (HBsAg) kinetics
      in chronic hepatitis B patients during long-term entecavir treatment. METHODS:
      This retrospective study included treatment-naive chronic hepatitis B patients
      who received at least 2 years of consecutive entecavir treatment. Patients were
      followed up at three to six month intervals with liver biochemistry, hepatitis B
      virus DNA, and abdominal sonography. In hepatitis B e antigen (HBeAg)-positive
      patients, HBeAg levels were assessed every three to six month until results
      became negative. Serum HBsAg levels were determined at the baseline, one-year and
      five-year time points. Liver cirrhosis was diagnosed through liver biopsy,
      imaging examinations, or clinical findings of portal hypertension. Hepatocellular
      carcinoma was diagnosed by histological examination or dynamic image studies.
      RESULTS: A total of 211 patients were enrolled. The median treatment time was
      5.24 (2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg
      levels were associated with an earlier virological response, earlier hepatitis B
      e antigen (HBeAg) seroconversion, and earlier biochemical response in HBeAg
      positive patients (cut-off value: 4 log IU/mL) and an earlier virological
      response in HBeAg-negative non-cirrhotic patients (cut-off value: 2.4 log IU/mL).
      Although HBsAg levels decreased slowly during long-term entecavir treatment,
      higher HBsAg decrease rates were found in the first year for HBeAg-positive non
      cirrhotic patients, and patients with higher baseline HBsAg levels. More
      favorable clinical outcomes were not observed by a rapid HBsAg decline per se,
      but depended on lower baseline HBsAg levels. CONCLUSION: Baseline HBsAg can be
      used to predict treatment responses. HBsAg levels and decrease rates should be
      considered together according to disease status while interpreting HBsAg changes.

PMID- 29456412
TI  - Performance of transient elastography in assessing liver fibrosis in patients
      with autoimmune hepatitis-primary biliary cholangitis overlap syndrome.
AB  - AIM: To investigate the performance of transient elastography (TE) for diagnosis
      of fibrosis in patients with autoimmune hepatitis-primary biliary cholangitis
      (AIH-PBC) overlap syndrome. METHODS: A total of 70 patients with biopsy-proven
      AIH-PBC overlap syndrome were included. Spearman correlation test was used to
      analyze the correlation of liver stiffness measurement (LSM) and fibrosis stage.
      Independent samples Student's t-test or one-way analysis of variance was used to
      compare quantitative variables. Receiver operating characteristics (ROC) curve
      was used to calculate the optimal cut-off values of LSM for predicting individual
      fibrosis stages. A comparison on the diagnostic accuracy for severe fibrosis was
      made between LSM and other serological scores. RESULTS: Patients with AIH-PBC
      overlap syndrome had higher median LSM than healthy controls (11.3 +/- 6.4 kPa vs
      4.3 +/- 1.4 kPa, P < 0.01). LSM was significantly correlated with fibrosis stage
      (r = 0.756, P < 0.01). LSM values increased gradually with an increased fibrosis
      stage. The areas under the ROC curves of LSM for stages F >= 2, F >= 3, and F4
      were 0.837 (95%CI: 0.729-0.914), 0.910 (0.817-0.965), and 0.966 (0.893-0.995),
      respectively. The optimal cut-off values of LSM for fibrosis stages F >= 2, F >=
      3, and F4 were 6.55, 10.50, and 14.45 kPa, respectively. LSM was significantly
      superior to fibrosis-4, glutaglumyl-transferase/platelet ratio, and aspartate
      aminotransferase-to-platelet ratio index scores in detecting severe fibrosis (F
      >= 3) (0.910 vs 0.715, P < 0.01; 0.910 vs 0.649, P < 0.01; 0.910 vs 0.616, P <
      0.01, respectively). CONCLUSION: TE can accurately detect hepatic fibrosis as a
      non-invasive method in patients with AIH-PBC overlap syndrome.

PMID- 29456413
TI  - Value of contrast-enhanced ultrasound in the differential diagnosis of
      gallbladder lesion.
AB  - AIM: To describe contrast-enhanced ultrasound (CEUS) features and evaluate
      differential diagnosis value of CEUS and conventional ultrasound for patients
      with benign and malignant gallbladder lesions. METHODS: This study included 105
      gallbladder lesions. Before surgical resection and pathological examination,
      conventional ultrasound and CEUS were performed to examine for lesions. Then, all
      the lesions were diagnosed as (1) benign, (2) probably benign, (3) probably
      malignant or (4) malignant using both conventional ultrasound and CEUS. The CEUS
      features of these gallbladder lesions were analyzed and diagnostic efficiency
      between conventional ultrasound and CEUS was compared. RESULTS: There were total
      17 cases of gallbladder cancer and 88 cases of benign lesion. Some gallbladder
      lesions had typical characteristics on CEUS (e.g., gallbladder adenomyomatosis
      had typical characteristics of small nonenhanced areas on CEUS). The sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy of
      CEUS were 94.1%, 95.5%, 80.0%, 98.8% and 95.2%, respectively. These were
      significantly higher than conventional ultrasound (82.4%, 89.8%, 60.9%, 96.3% and
      88.6%, respectively). CEUS had an accuracy of 100% for gallbladder sludge and
      CEUS helped in differential diagnosis among gallbladder polyps, gallbladder
      adenoma and gallbladder cancer. CONCLUSION: CEUS may provide more useful
      information and improve the diagnosis efficiency for the diagnosis of gallbladder
      lesions than conventional ultrasound.

PMID- 29456414
TI  - High prevalence of hepatitis B-antibody loss and a case report of de novo
      hepatitis B virus infection in a child after living-donor liver transplantation.
AB  - AIM: To assess the seroprevalence of hepatitis B virus (HBV) immunity among
      previously vaccinated pediatric liver transplant recipients and present a case
      report of de novo hepatitis B infection after liver transplantation. METHODS:
      This study focused on children with chronic liver diseases who received primary
      hepatitis B immunization and had a complete dataset of anti-HBs before and after
      liver transplantation between May 2001 and June 2017. Medical records were
      retrospectively reviewed for potential factors relating to HBV immunity loss.
      RESULTS: In total, 50 children were recruited. The mean time from liver
      transplantation to anti-HBs testing was 2.53 +/- 2.11 years. The mean anti-HBs
      levels before and after liver transplantation were 584.41 +/- 415.45 and 58.56 +/
      6.40 IU/L, respectively. The rate of non-immunity (anti-HBs < 10 IU/L) in the
      participants was 46% (n = 26) at one year, 57% (n = 7) at two years and 82% (n =
      17) at > three years following liver transplantation. The potential factors
      relating to HBV immunity loss after liver transplantation were identified as anti
      HBs (P = 0.002), serum albumin (P = 0.04), total bilirubin (P = 0.001) and direct
      bilirubin (P = 0.003) before liver transplantation. A five-year-old boy with
      biliary cirrhosis received 4 doses of HBV vaccine with an anti-HBs titer of >
      1000 IU/L and underwent liver transplantation; his anti-HBc-negative father was
      the donor. After liver transplantation, the boy had stenosis of the hepatic
      artery up to the inferior vena cava anastomosis and underwent venoplasty three
      times. He also received subcutaneous injections of enoxaparin for 5 mo and 20
      transfusions of blood components. Three years and ten months after the liver
      transplantation, transaminitis was detected with positive tests for HBsAg, HBeAg,
      and anti-HBc (2169.61, 1706 and 8.45, respectively; cutoff value: < 1.00) and an
      HBV viral load of 33212320 IU/mL. CONCLUSION: The present study showed that loss
      of hepatitis B immunity after liver transplantation is unexpectedly common. In
      our case report, despite high levels of anti-HBs prior to transplantation,
      infection occurred at a time when, unfortunately, the child had lost immunity to
      hepatitis B after liver transplantation.

PMID- 29456415
TI  - Gastroenteritis in an adult female revealing hemolytic uremic syndrome: Case
      report.
AB  - Nowadays acute gastroenteritis infection caused by Escherichia coli (E. coli)
      O157:H7 is frequently associated with hemolytic uremic syndrome (HUS), which
      usually developed after prodromal diarrhea that is often bloody. The abdominal
      pain accompanied by failure kidney is a suspicious symptom to develop this
      disorder. Their pathological characteristic is vascular damage which manifested
      as arteriolar and capillary thrombosis with abnormalities in the endothelium and
      vessel walls. The major etiological agent of HUS is enterohemorragic (E coli)
      strain belonging to serotype O157:H7. The lack of papers about HUS associated to
      gastroenteritis lead us to report this case for explain the symptoms that are
      uncommon. Furthermore, this report provides some strategies to suspect and make
      an early diagnosis, besides treatment approach to improving outcomes and
      prognosis for patients with this disorder.

PMID- 29456416
TI  - Endpoint regularity of discrete multisublinear fractional maximal operators
      associated with [Formula: see text]-balls.
AB  - In this paper we investigate the endpoint regularity of the discrete m-sublinear
      fractional maximal operator associated with [Formula: see text]-balls, both in
      the centered and uncentered versions. We show that these operators map [Formula:
      see text] into [Formula: see text] boundedly and continuously. Here [Formula: see
      text] represents the set of functions of bounded variation defined on [Formula:
      see text].

PMID- 29456417
TI  - Orlicz-Garling sequence spaces of difference operator and their domination in
      Orlicz-Lorentz spaces.
AB  - We introduce new classes of generalized Orlicz-Garling sequences and Orlicz
      Lorentz sequences by using a sequence of Orlicz functions and difference
      operator. We show that the Orlicz-Garling sequence space admits a unique 1
      subsymmetric basis and a 1-dominated block basic sequence in [Formula: see text].
      We also make an effort to prove that every symmetric normalized block Orlicz
      Garling sequence dominates an Orlicz-Lorentz sequence. Finally, we study some
      geometric properties of these spaces and establish some inclusion relations
      between spaces.

PMID- 29456418
TI  - Study of weak solutions for parabolic variational inequalities with nonstandard
      growth conditions.
AB  - In this paper, we study the degenerate parabolic variational inequality problem
      in a bounded domain. First, the weak solutions of the variational inequality are
      defined. Second, the existence and uniqueness of the solutions in the weak sense
      are proved by using the penalty method and the reduction method.

PMID- 29456419
TI  - Zipf-Mandelbrot law, f-divergences and the Jensen-type interpolating
      inequalities.
AB  - Motivated by the method of interpolating inequalities that makes use of the
      improved Jensen-type inequalities, in this paper we integrate this approach with
      the well known Zipf-Mandelbrot law applied to various types of f-divergences and
      distances, such are Kullback-Leibler divergence, Hellinger distance,
      Bhattacharyya distance (via coefficient), [Formula: see text]-divergence, total
      variation distance and triangular discrimination. Addressing these applications,
      we firstly deduce general results of the type for the Csiszar divergence
      functional from which the listed divergences originate. When presenting the
      analyzed inequalities for the Zipf-Mandelbrot law, we accentuate its special
      form, the Zipf law with its specific role in linguistics. We introduce this
      aspect through the Zipfian word distribution associated to the English and
      Russian languages, using the obtained bounds for the Kullback-Leibler divergence.

PMID- 29456420
TI  - Timely News for the Multidisciplinary Care Team.
AB  - Welcome to Diabetes Spectrum's first installment of Diabetes is Primary, a round
      up of the latest diabetes developments for health care providers. In this issue,
      we take a look at radical weight loss for diabetes remission, Hong Kong's
      diabetes risk assessment and management program, personalized A1C targets, and
      diabetes diagnoses. The American Diabetes Association (ADA) and European
      Association for the Study of Diabetes (EASD) panel gives its verdict on
      continuous glucose monitoring (CGM) devices, and we learn how Medicare will soon
      pay for a diabetes prevention program.

PMID- 29456423
TI  - Evaluating the Implementation of the EndoTool Glycemic Control Software System.
AB  - Purpose: The purpose of this study was to compare achievement of glycemic control
      on insulin drips before and after the implementation of EndoTool, a glucose
      management software system used in a community hospital setting. Methods: A
      retrospective chart review was performed of patients on an insulin drip who were
      managed before and after implementation of the EndoTool software. Fifty patients
      were selected for each group. Statistical analyses were run to compare metrics
      gathered between groups. Results: Patients in the standard care group were on an
      insulin drip for an average of 23.9 hours compared to 20.9 hours in the EndoTool
      group (P = 0.38). Hypoglycemia occurred at an average rate of 0.036 events per
      patient in the standard group and 0.007 events per patient in the EndoTool group
      (P = 0.17). The average rate of hyperglycemia was 0.358 events per patient in the
      standard group and 0.283 events per patient in the EndoTool group (P = 0.25). The
      average time to achieve the blood glucose target was 2.78 and 3.67 hours in the
      standard and EndoTool groups, respectively (P = 0.27). Total patient values were
      within target range 45.2% of the time in the standard care group and 47.3% of the
      time in the EndoTool group (P = 0.71). Conclusion: Analysis of the implementation
      of EndoTool in the community hospital setting found no statistically significant
      differences between groups, although rates of hypo- and hyperglycemia showed a
      trend toward improved safety in the EndoTool group. These results could be
      attributed to the conservative parameters the hospital set in the initial phase
      of EndoTool implementation.

PMID- 29456422
TI  - Understanding the Meaning of Food in People With Type 2 Diabetes Living in
      Northern Appalachia.
AB  - Purpose: Food and eating convey memories and feelings and serve important
      functions in creating and maintaining relationships. Given the increasing rate of
      diabetes in the United States, research understanding the meaning of food may
      shed light on how patients negotiate everyday food choices while managing type 2
      diabetes. The purpose of this qualitative study was to explore the meaning of
      food among adults with type 2 diabetes living in Northern Appalachia. Methods: In
      depth, face-to-face interviews were conducted with type 2 diabetes patients.
      Interviews were coded and analyzed via thematic analysis. Results: Nineteen
      adults with type 2 diabetes (mean age 68.7 +/- 10.6 years, mean A1C 7.4 +/- 1.4%,
      mean diabetes duration 10.9 +/- 11.9 years, 52.6% female, 100% white)
      participated in the study. Qualitative analysis revealed three themes: 1)
      "Sustaining Life:" Food and the Demands of Diabetes Management, in which
      participants described the role of food as operational and said that eating was
      dictated by time rather than hunger or pleasure; 2) "Diabetes Feels Like a Yield
      Sign:" Diabetes Changes Perceptions of Food, Enjoyment, and Social Relationships,
      in which most participants described a negative or ambivalent relationship with
      food after their diabetes diagnosis; and 3) "Food is Everywhere; It's Seducing:"
      Struggling With Diabetes Management in a Fast-Food Culture, in which participants
      discussed how the American fast-food culture was in direct conflict with the
      demands of diabetes and described how they struggled to follow a healthful diet
      in a culture that advertised the opposite in many venues. Conclusion: Adults with
      diabetes may benefit from education that addresses both the personal and
      sociocultural factors that guide food choices.

PMID- 29456424
TI  - Diabetes Risk Assessment in Latinas: Effectiveness of a Brief Diabetes Risk
      Questionnaire for Detecting Prediabetes in a Community-Based Sample.
AB  - Objective: Numerous validated questionnaires use self-reported data to quantify
      individuals' risk of having diabetes or developing it in the future. Evaluations
      of these tools have primarily used nationally representative data, limiting their
      application in clinical and community settings. This analysis tested the
      effectiveness of the American Diabetes Association (ADA) risk questionnaire for
      identifying prediabetes in a community-based sample of Latinas. Methods: Data
      were collected using the ADA risk questionnaire and assessing A1C. Among 204
      participants without diabetes, we examined the association between individual
      characteristics and glycemic status. We then calculated the performance
      characteristics (sensitivity, specificity, positive predictive value [PPV], and
      negative predictive value [NPV]) of the ADA risk questionnaire for detecting
      prediabetes, using A1C results as the gold standard to define the outcome.
      Results: All participants were women of self-reported Hispanic/Latino ethnicity.
      Their mean ADA risk score was 5.6 +/- 1.6. Latinas who had prediabetes were
      older, with significantly higher rates of hypertension and a higher ADA risk
      score than those without prediabetes. At a risk score >=5-the threshold for high
      risk set by the ADA-the questionnaire had the following test performance
      characteristics: sensitivity 77.8%, specificity 41.7%, PPV 76.2%, and NPV 43.9%.
      Conclusion: The ADA risk questionnaire demonstrates reasonable performance for
      identifying prediabetes in a community-based sample of Latinas. Our data may
      guide other groups' use of this tool in the same target population. Future
      research should examine the effectiveness of this questionnaire for recruiting
      diverse populations into diabetes prevention programs. In addition, unique
      diabetes risk assessment tools for specific target populations are needed and may
      outperform questionnaires developed using nationally representative data.

PMID- 29456425
TI  - Reasons for Open and Closed Attitudes Regarding Type 1 Diabetes.
AB  - Thirty-one adults with type 1 diabetes participated in this qualitative study to
      explore reasons why they were willing (had an open attitude) or unwilling (had a
      closed attitude) to disclose diabetes-related information to others. Participants
      (61.3% female, mean age 38.48 years, mean duration of diabetes 21.94 years, 100%
      white) answered open-ended questions about living with type 1 diabetes.
      Interviews were transcribed verbatim and coded to identify major patterns that
      emerged in the data. Reasons for open attitudes included support from others,
      confidence and feeling comfortable, feeling normal despite diabetes, seeking to
      educate, and feeling that it was not a major concern to share information with
      others. Reasons for closed attitudes included fear of discrimination,
      misunderstanding from others, embarrassment and shame, and feeling that it was
      not a major concern to share information. A higher number of participants
      reported open attitudes after diagnosis than at initial diagnosis; a lower number
      of participants reported closed attitudes after diagnosis than at initial
      diagnosis. Professionals should consider effective forms of type 1 diabetes
      related education to reduce diabetes misconceptions and discrimination against
      diagnosed individuals. This may help individuals feel more open and willing to
      adhere to and seek assistance with their diabetes-related self-care.

PMID- 29456426
TI  - Influences on Diabetes Self-Management Education Participation in a Low-Income,
      Spanish-Speaking, Latino Population.
AB  - Objective: To investigate influences on participation in diabetes self-management
      education (DSME) classes in a low-income, Spanish-speaking, Latino population.
      Methods: Fifteen patients from an Oregon clinic participated in semi-structured
      interviews designed to understand influences on their participation in DSME
      classes, and the authors conducted a thematic analysis. Results: Four themes
      characterized the data: 1) limited resources, 2) culture, 3) relationship with
      diabetes, and 4) relationship with clinic. Barriers to class attendance included
      lack of time, childcare, and transportation; male participants' shame of illness
      and lack of interest in health; and difficulty contacting participants by
      telephone. Motivators of class attendance included interest in being healthy for
      the sake of family; interest in nutrition; knowledge of the effects of diabetes
      on self, friends, and family; and positive experiences with group support and
      self-efficacy in class. Practice implications and conclusion: Participation in
      DSME classes in this low-income, Spanish-speaking, Latino population was
      influenced by many factors. Understanding these factors is an important step
      toward creating classes that are successful in increasing attendance rates for
      this and similar populations. Creative, targeted approaches to designing DSME
      classes for low-income, Spanish-speaking, Latino patients and similar populations
      are needed. These may include classes that remove the barriers of shame and lack
      of interest for male participants; focus on family involvement, celebration of
      culturally appropriate foods, group support, and self-efficacy; are accessible to
      resource-limited participants; and use alternative methods to recruit hard-to
      reach participants.

PMID- 29456428
TI  - Strategies to Improve Prevention and Management in Diabetic Retinopathy:
      Qualitative Insights from a Mixed-Methods Study.
AB  - Nonproliferative and proliferative diabetic retinopathy (DR) are common,
      progressive complications of diabetes with a rising incidence. Over time,
      patients with nonproliferative DR may progress to more advanced stages of DR,
      with an increased risk of vision-threatening conditions such as diabetic macular
      edema (DME). DME is the most frequent cause of vision loss in patients with
      diabetes and eventually can lead to blindness. Early-stage DR is asymptomatic;
      therefore, a coordinated management strategy is crucial to prevent or limit the
      progression of DR. Such a strategy includes regular screening for DR risk
      factors, glycemic control, and prompt diagnosis of DR. Preventive care should
      include a comprehensive dilated eye exam, ancillary tests, and patient education
      involving a multidisciplinary team composed of ophthalmologists, retina
      specialists, and primary diabetes care providers, including primary care
      providers and endocrinologists/diabetologists. However, although guideline
      recommendations for regular screening and patient education are well
      disseminated, many people with diabetes are not receiving ophthalmological care
      that could prevent visual impairment and blindness. We designed a mixed-methods
      study to explore the impact of patient-focused education on patient knowledge and
      self-efficacy in relation to DR prevention and management and to assess how
      online education can help to change patient knowledge, competence, and practice.
      Analysis of in-depth, qualitative data involving people with diabetes with or
      without DR collected 5-16 weeks after education participation shows that online
      patient education is an effective tool in building patient knowledge and
      awareness about DR and in motivating action in DR self-care.

PMID- 29456427
TI  - The Experience of Diabetes-Related Language in Diabetes Care.
AB  - Objective: The goal of this study was to understand how adults with diabetes
      experience the words used in diabetes care. Methods: This qualitative study
      guided by Critical Theory used two virtual and two in-person focus groups
      conducted by the same facilitator. A total of 68 focus group members
      participated. The facilitator transcribed and coded focus group data using
      individual responses as the unit of analysis. The facilitator used constant
      comparison to analyze responses and developed a research summary of themes that
      emerged. A second coder confirmed the themes originally identified, and
      participants provided feedback on the summary. Results: Many negative and
      stigmatizing words are used in diabetes care. Several themes emerged from the
      data, including judgment; fear and anxiety; labels, reminders, and assumptions;
      oversimplification and directives; misunderstanding, misinformation, and
      disconnection; and body language and tone. Participants reported experiencing
      negative diabetes-related words in the general public, with their health care
      providers (HCPs), and in the media. Participants made suggestions for HCPs to
      replace negative words; they raised a concern that current negative words will be
      replaced by others with similar negative connotations; and they said they would
      feel more like a partner in their care if HCPs stopped using these words.
      Conclusion: The language used in diabetes care has an impact on people who live
      with the disease. Awareness is the first step in eradicating stigma in diabetes
      care. HCPs can improve patient-provider communication and contribute to a more
      positive experience for people living with diabetes by choosing words that
      empower.

PMID- 29456429
TI  - Influence of Health Status on the Association Between Diabetes and Depression
      Among Adults in Europe: Findings From the SHARE International Survey.
AB  - Objective: The association between diabetes and depression, a common health
      comorbidity in people with diabetes, has been recognized but not well understood.
      The purpose of this study was to explore the association between diabetes and
      depression in a large international sample of adults, adjusting for demographics,
      socioeconomic status, behavioral risks, and current health status. Methods: The
      association between diabetes and depression was assessed in a sample of 57,004
      Europeans >=50 years of age from 15 European countries using data from the fifth
      wave of SHARE (the Survey of Health, Ageing, and Retirement in Europe). Multiple
      logistic regression models of the association between diabetes and depression
      were conducted, adjusting for potential confounders. Results: Analyses showed
      that, despite diabetes being associated with depression in crude and partially
      adjusted models, further adjustment for self-perceived health made the
      association between diabetes and depression no longer statistically significant
      (odds ratio 1.0, 95% CI 0.9-1.0). Conclusion: Adjustment for a variety of
      demographic, socioeconomic, behavioral risk, and health status variables reduced
      the estimated association between diabetes and depression until it was no longer
      significant. Further research should explore the specific symptoms of distress
      characterized in people with diabetes.

PMID- 29456430
TI  - Effect of Medical Nutrition Therapy for Patients With Type 2 Diabetes in a Low
      /No-Cost Clinic: A Propensity Score-Matched Cohort Study.
AB  - Background: Although many studies have been conducted regarding the effectiveness
      of medical nutrition therapy (MNT) for type 2 diabetes management, less is known
      about the effectiveness of MNT for low-income adults. This study evaluated the
      contribution of MNT in improving A1C and blood pressure in a population of low
      income adults with type 2 diabetes. Methods: This was a population-based,
      propensity score-matched cohort study using provincial health data from Altoona,
      Blair County, Pa. Patients who had been diagnosed with type 2 diabetes for at
      least 6 months before March 2014 were selected from two separate clinics that
      serve low-income populations. Patients who received MNT (n = 81) from a
      registered dietitian were compared to a matched group of patients who received
      primary care alone (n = 143). Outcome measures were A1C and systolic and
      diastolic blood pressure. The follow-up period was 1 year. Results: Improvements
      in A1C and systolic and diastolic blood pressure were statistically significant
      for patients who received MNT at uniform 3-month intervals through 1 year. At the
      1-year follow-up, A1C reduction was -0.8% (P <0.01), systolic blood pressure
      reduction was -8.2 mmHg (P <0.01), and diastolic blood pressure reduction was 
      4.3 mmHg (P <0.05). Conclusion: Although low-income individuals encounter a
      variety of barriers that reduce their capacity for success with and adherence to
      MNT, provision of nutrition therapy services by a registered dietitian
      experienced in addressing these barriers can be an effective addition to the
      existing medical components of type 2 diabetes care.

PMID- 29456431
TI  - Evaluation of Diabetes Education and Pharmacist Interventions in a Rural, Primary
      Care Setting.

PMID- 29456432
TI  - Consequences of Undocumented Medication Use.

PMID- 29456433
TI  - The Pillars of Prevention: Discover, Advocate, and Educate.
AB  - EDITOR'S NOTE: This article is adapted from a speech that Ms. Montgomery
      delivered as the American Diabetes Association's President of Health Care &
      Education at ADA's Annual Meeting and Scientific Sessions in June 2017, San
      Diego, Calif. A webcast of the speech can be viewed on ADA's DiabetesPro website
      at https://professional.diabetes.org/webcasts-ss2017.

PMID- 29456434
TI  - A Toast to Our History.
AB  - EDITOR'S NOTE: This article is adapted from the address Ms. Kruger delivered as
      the recipient of the American Diabetes Association's Outstanding Educator in
      Diabetes Award for 2017. She delivered the address in June 2017 at the
      Association's 77th Annual Meeting and Scientific Sessions in San Diego, Calif. A
      webcast of the speech can be viewed on ADA's DiabetesPro website at
      https://professional.diabetes.org/webcasts-ss2017.

PMID- 29456435
TI  - Your Exclusion, My Inclusion: Reflections on a Career Working With the Most
      Challenging and Vulnerable in Diabetes.
AB  - EDITOR'S NOTE: This article is adapted from the address Dr. Harris delivered as
      the recipient of the American Diabetes Association's Richard R. Rubin Award for
      2017. This award recognizes a behavioral researcher who has made outstanding,
      innovative contributions to the study and understanding of the behavioral aspects
      of diabetes in diverse populations. Dr. Harris delivered the address in June 2017
      at the Association's 77th Scientific Sessions in San Diego, Calif.

PMID- 29456436
TI  - Learning Activity Predictors from Sensor Data: Algorithms, Evaluation, and
      Applications.
AB  - Recent progress in Internet of Things (IoT) platforms has allowed us to collect
      large amounts of sensing data. However, there are significant challenges in
      converting this large-scale sensing data into decisions for real-world
      applications. Motivated by applications like health monitoring and intervention
      and home automation we consider a novel problem called Activity Prediction, where
      the goal is to predict future activity occurrence times from sensor data. In this
      paper, we make three main contributions. First, we formulate and solve the
      activity prediction problem in the framework of imitation learning and reduce it
      to a simple regression learning problem. This approach allows us to leverage
      powerful regression learners that can reason about the relational structure of
      the problem with negligible computational overhead. Second, we present several
      metrics to evaluate activity predictors in the context of real-world
      applications. Third, we evaluate our approach using real sensor data collected
      from 24 smart home testbeds. We also embed the learned predictor into a mobile
      device-based activity prompter and evaluate the app for 9 participants living in
      smart homes. Our results indicate that our activity predictor performs better
      than the baseline methods, and offers a simple approach for predicting activities
      from sensor data.

PMID- 29456437
TI  - A Tabletop Persistent-Mode, Liquid-Helium-Free, 1.5-T/90-mm MgB2 "Finger" MRI
      Magnet for Osteoporosis Screening: Two Design Options.
AB  - In this paper we present two design options for a tabletop liquid-helium-free,
      persistent-mode 1.5-T/90-mm MgB2 "finger" MRI magnet for osteoporosis screening.
      Both designs, one with and the other without an iron yoke, satisfy the following
      criteria: 1) 1.5-T center field with a 90-mm room-temperature bore for a finger
      to be placed at the magnet center; 2) spatial field homogeneity of <5 ppm over a
      20-mm diameter of spherical volume (DSV); 3) persistent-mode operation with
      temporal stability of <0.1 ppm/hr; 4) liquid-helium-free operation; 5) 5-gauss
      fringe field radius of <50 cm from the magnet center; and 6) small and light
      enough for placement on an exam table. Although the magnet is designed to operate
      nominally at 10 K, maintained by a cryocooler, it has a 5-K temperature margin to
      keep its 1.5-T persistent field up to 15 K. The magnet will be immersed in a
      volume of solid nitrogen (SN2) that provides additional thermal mass when the
      cryocooler is switched off to provide a vibration-free measurement environment.
      The SN2 enables the magnet to maintain its persistent field over a period of time
      sufficient for quiescent measurement, while still limiting the magnet operating
      temperature to <=15 K. We discuss first pros and cons of each design, and then
      further studies of our proposed MgB2 finger MRI magnet.

PMID- 29456438
TI  - Barriers to Participation in Parenting Programs: The Relationship between
      Parenting Stress, Perceived Barriers, and Program Completion.
AB  - Families experiencing child maltreatment or risk factors for child maltreatment
      often receive referrals to interventions focused on changing parenting practices.
      Compliance with specific parenting programs can be challenging as many of the
      stressors that place families at-risk may also interfere with program
      participation. Because families may receive limited benefit from programs they do
      not fully receive, it is critical to understand the relationship between
      parenting stress and barriers to program completion. We used structural equation
      modeling to examine the relationship among parenting stress, perceived barriers
      to program participation, and program completion in two datasets involving low
      income parents. Data were collected at two time points from a sample of parents
      involved with child welfare services and a sample of parents considered at-risk
      of future involvement (total study n = 803). Direct paths from parenting stress
      at time 1 to barriers to participation and parenting stress at time 2, and from
      parenting stress at time 2 to program completion were significant. Interestingly,
      increased barriers to participation were related to increased parenting stress at
      time 2, and greater parenting stress was related to increased program completion.
      Results suggest that with increasing levels of parenting stress, parents have an
      increased likelihood of completing the program. Assessing and addressing the
      influence of perceived barriers and parenting stress on program participation may
      decrease the likelihood of treatment attrition.

PMID- 29456439
TI  - Parent Training and Skill Acquisition and Utilization Among Spanish- and English
      Speaking Latino Families.
AB  - In the U.S., there is a growing Latino population, in which parents primarily
      speak Spanish to their children. Despite the evidence that language preference is
      associated with level of acculturation and influences parenting practices in
      these families, no study has compared how Spanish-and English-speaking Latino
      families acquire and utilize the skills taught during parent-training programs
      such as Parent-Child Interaction Therapy (PCIT). Twenty-seven mother-infant
      Latino dyads received a home-based adaptation of the Child-Directed Interaction
      (CDI) phase of PCIT as part of a larger randomized control trial. Most infants
      were male (63%), and their average age was 13.7 months (SD = 1.43). Most families
      (52%) lived below the poverty line. The Dyadic Parent-Child Interaction Coding
      System-Third Edition (DPICS-III) was employed to evaluate PCIT skills at baseline
      and post-treatment, as well as at 3- and 6-month follow-up, assessments. We
      conducted multiple linear regression analyses among Spanish-speaking (55%) and
      English-speaking (45%) families to examine differences in acquisition and
      utilization of do and don't skills at each assessment while controlling for
      mother's education. Results yielded no group differences in the acquisition rate
      of do or don't skills at any time point. However, Spanish-speaking mothers used
      significantly more don't skills than English-speaking mothers at each assessment.
      Specifically, Spanish-speaking families used significantly more commands at
      baseline, post-treatment, and the 6-month followup assessments, as well as more
      questions at post-treatment and at the 6-month follow-up assessments. These
      findings highlight the importance of addressing cultural values such as respeto
      to ensure culturally robust parent-training programs for Latino families.

PMID- 29456441
TI  - We need to debate the value of manipulative therapy and recognize that we do not
      always understand from what to attribute our success.

PMID- 29456440
TI  - Maltreated Children Use More Grammatical Negations.
AB  - Many studies reveal a strong impact of childhood maltreatment on language
      development, mainly resulting in shorter utterances, less rich vocabulary, or a
      delay in grammatical complexity. However, different theories suggest the
      possibility for resilience-a positive adaptation to an otherwise adverse
      environment-in children who experienced childhood maltreatment. Here, we
      investigated different measures for language development in spontaneous speech,
      examining whether childhood maltreatment leads to a language deficit only or
      whether it can also result in differences in language use due to a possible
      adaptation to a toxic environment. We compared spontaneous speech during
      therapeutic peer-play sessions of 32 maltreated and 32 non-maltreated children
      from the same preschool and equivalent in gender, age (2 to 5 years), home
      neighborhood, ethnicity, and family income. Maltreatment status was reported by
      formal child protection reports, and corroborated by independent social service
      reports. We investigated general language sophistication (i.e., vocabulary,
      talkativeness, mean length of utterance), as well as grammatical development
      (i.e., use of plurals, tense, grammatical negations). We found that maltreated
      and non-maltreated children showed similar sophistication across all linguistic
      measures, except for the use of grammatical negations. Maltreated children used
      twice as many grammatical negations as non-maltreated children. The use of this
      highly complex grammatical structure shows an advanced linguistic skill, which
      shows that childhood maltreatment does not necessarily lead to a language
      deficit. The result might indicate the development of a negativity bias in the
      structure of spontaneous language due to an adaptation to their experiences.

PMID- 29456442
TI  - The effect of direction specific thoracic spine manipulation on the cervical
      spine: a randomized controlled trial.
AB  - Objectives: To determine the difference on neck outcomes with directional
      manipulation to the thoracic spine. There is evidence that thoracic spine
      manipulation is effective in treating patients with neck pain. However, there is
      no research that determines if the assessment of directional hypomobility and the
      selection of thrust direction offer improved outcomes. Methods: A total of 69
      patients with cervical spine pain were randomly assigned to receive either a
      manipulation that was consistent with their thoracic spine motion loss (matched)
      or opposite their motion loss (unmatched). The patient was given care consistent
      with the orthopedic section guidelines for neck pain and the physical therapist's
      clinical reasoning. Baseline outcome measures (NPRS, NDI, GROC) were taken and
      reassessed two days and two weeks after treatment. Results: Both groups had
      positive results when pain, neck disability index, and global rating of change
      were assessed. There was no difference between the matched and unmatched groups.
      Discussion: Directional manipulation of hypomobile thoracic spine segments may
      not be required to improved outcomes in patients with neck pain. Future studies
      should assess a variety of factors when determining the best available treatment,
      including manual therapy procedures, exercise, and patient selection. Level of
      Evidence: 1b.

PMID- 29456443
TI  - The screening process of a patient with low back pain and suspected thoracic
      myelopathy: a case report.
AB  - Background: Thoracic disc herniations are rare and difficult to diagnose.
      Myelopathy is a potential consequence that can lead to irreversible neurological
      impairment if not treated appropriately. It is incumbent on all clinicians who
      see patients with low back pain (LBP) to be aware of such pathologies. This case
      describes a screening process in the detection of a rare serious spinal pathology
      and discusses the use of red flags and central nervous system signs and symptoms
      in the decision leading to immediate referral. Case Description: The subject in
      this case was a 69-year-old male referred to physical therapy for the treatment
      of LBP after having seen two medical doctors. He presented with severe spinal
      pain with gait disturbance, postural balance deficits and bilateral loss of
      plantar flexor strength. Decreased sensation in the buttocks and a subtle episode
      of urinary incontinence were also present. Outcomes: Based on the results of the
      history and physical examination, the patient was referred back to his medical
      practitioner, who ordered magnetic resonance imaging. A thoracic disc herniation
      associated with spondyloarthritis at T10-11 causing myelopathy was detected, and
      the patient underwent immediate decompressive surgery. One month following
      initial evaluation, the patient had completely recovered without any neurological
      compromise. Discussion: This case highlights the importance of the screening of
      serious pathologies and the assessment of central nervous impairments in certain
      cases of LBP. The integration of a cluster of subjective and physical examination
      findings led to the prompt referral of this patient for urgent medical attention.
      Level of Evidence: 4.

PMID- 29456444
TI  - Pain pattern classification and directional preference are associated with
      clinical outcomes for patients with low back pain.
AB  - Pain Pattern Classification (PPC) and Directional Preference (DP) have shown
      merit as reliable and predictable clinical solutions to help reduce the burden
      posed by low back pain (LBP). We conducted a prospective, observational cohort
      study to verify the association between PPC, DP, and clinical outcomes. We
      hypothesized that (1) patients who demonstrated DP Centralization (CEN) would
      have lower pain intensity and disability at follow-up than patients who
      demonstrated Non-DP Non-CEN, and (2) the prevalence of DP at first examination
      would be lowest for patients with chronic LBP and are greater than 65 years old.
      First examination and follow-up data were completed by 639 patients. Clinical
      outcome measures, including pain intensity and disability, were collected at
      first examination and follow-up. Baseline comparisons were made between groups
      with first examination data only and groups with first examination data and
      follow-up data. A Pearson's chi-squared test was used to determine differences in
      prevalence rates for the categorical variables, and two-sample t-tests were used
      for the continuous variables. A Turkey's range test was used to determine
      differences in follow-up pain intensity and disability for LBP dual
      classifications. Multiple regression was used to investigate DP prevalence
      considering risk adjusted factors. Overall prevalence of DP was 84.5% and
      prevalence was lowest for patients with sub-acute symptoms. No significant
      difference existed for the prevalence of DP for patients based on age. Patients
      classified as DP CEN had, on average, 1.99 pain intensity units less than
      patients classified as Non-DP Non-CEN at follow-up. Patients classified as DP CEN
      had, on average, 3.43 RMDQ units less than patients classified as Non-DP Non-CEN
      at follow-up.These findings support previous reports, verifying the association
      between LBP dual-classification schemes and clinical outcomes.

PMID- 29456446
TI  - Prevalence and reliability of treatment-based classification for subgrouping
      patients with low back pain.
AB  - Objectives: To observe the distribution of patients who presented with low back
      pain (LBP) and to determine the between therapists' interrater reliability of
      assessments in a private outpatient setting using treatment-based classification
      (TBC) subgroups. Methods: An observational and methodological study was
      conducted. Four hundred and twenty-nine patients (231 male; 198 female)
      presenting LBP symptoms and referred to conservative treatment were assessed by
      13 physical therapists who conducted a 60-min examination process utilizing TBC
      subgroups. Interrater reliability analyses from six raters were assessed using
      Fleiss' kappa and previously recorded data (n = 30). Results: In this study,
      65.74% of patients were classified in only one subgroup, the most prevalent being
      stabilization (21.91%), followed by extension (15.38%), traction (11.89%),
      flexion (10.96%), manipulation (5.13%), and lateral shift (0.47%). Approximately
      20.98% of patients were classified in two subgroups, where the most frequent
      overlaps were flexion + stabilization (7.46%), extension + stabilization (6.06%),
      flexion + traction (4.20%), extension + manipulation (1.86%), and 13.29% of
      patients were not classified in any TBC subgroup. Analysis of interrater
      reliability showed a kappa value of 0.62 and an overall agreement of 66% between
      raters. Discussion: LBP is a heterogeneous clinical condition and several
      classification methods are proposed in the attempt to observe better outcomes for
      patients. Eighty-five percent of patients assessed were able to be classified
      when using the TBC assessment and reliability analysis showed a substantial
      agreement between raters. Level of Evidence: 2c.

PMID- 29456445
TI  - Concurrent validation of a pressure pain threshold scale for individuals with
      myofascial pain syndrome and fibromyalgia.
AB  - Background: Manual pressure palpation is an examination technique used in the
      classification of myofascial pain syndrome (MPS) and fibromyalgia (FM).
      Currently, there are no validated systems for classifying results. A valid and
      reliable pressure pain threshold scale (PPTS) may provide a means for clinicians
      to grade, document, and report findings. The purpose of this investigation was to
      validate a PPTS in individuals diagnosed with MPS and FM. Intra-rater
      reliability, concurrent validity, minimum cut-off value, and patient responses
      were evaluated. Methods: Eighty-four participants who met the inclusion criteria
      were placed into three groups of 28 (N = 84): MPS, FM, and asymptomatic controls.
      All participants underwent a two-part testing session using the American College
      of Rheumatology criteria for classifying FM. Part-1 consisted of manual palpation
      with a digital pressure sensor for pressure consistency and part 2 consisted of
      algometry. For each tender point (18 total), participants graded tenderness using
      the visual analog scale (VAS) while the examiner concurrently graded response
      using a five-point PPTS. Results: The PPTS had good intra-rater reliability (ICC
      >= .88). A moderate to excellent relationship was found between the PPTS and VAS
      for all groups with the digital pressure sensor and algometer (rho >= .61). A
      minimum cut-off value of 2 on the PPTS differentiated participants with MPS and
      FM from asymptomatic controls. Discussion: The results provide preliminary
      evidence validating the PPTS for individuals with MPS and FM. Future research
      should further study the clinimetric properties of the PPTS with other chronic
      pain and orthopedic conditions. Levels of Evidence: 2c. Clinical Trial
      Registration: ClinicalTrials.gov registration No. NCT02802202.

PMID- 29456447
TI  - A preliminary analysis of outcomes and end range procedures used to achieve
      centralization in people with low back pain.
AB  - Objectives: To investigate the relationship between clinical outcome and the
      types of end range procedures used to achieve centralization in a sample of
      patients with low back pain (LBP) and/or peripheral symptoms. Methods: Small
      sample retrospective analysis of an observational cohort. Patients with LBP who
      centralized during initial visit at two physical therapy clinics were recruited
      to participate. The types of end range procedures used to achieve centralization
      were documented during each office visit and a chart review was performed after 4
      weeks. Outcomes were determined by improvement in the Oswestry Disability Index
      (ODI) score after 4 weeks. Statistical analysis determined the association
      between the types of end range procedures and outcomes. Results: Thirty-one
      patients gave consent to participate. Nineteen patients met inclusion criteria
      and were included in data analysis. After 4 weeks, the improvement in mean ODI
      scores was 15.89 +/- 16.28. Differing end range procedures were used to achieve
      centralization within this cohort. The types of end range procedures used to
      achieve centralization were not significantly associated with outcomes.
      Discussion: The results observed in this study promote exhausting many different
      types of end range procedures to determine if centralization can be achieved.
      Limiting the end range procedures used to assess centralization may fail to
      identify patients who can achieve centralization and subsequently have positive
      clinical outcomes. Larger cohort studies investigating relationships between
      outcomes and the types of end range procedures used to achieve centralization
      would contribute to management of people with LBP. Level of Evidence: 4.

PMID- 29456448
TI  - Pain catastrophizing mediates the relationship between trait happiness and
      depressive symptoms in individuals with current pain.
AB  - Objective: There is an extensive relationship between chronic pain and
      depression; however, there is less research examining whether pain-specific
      factors, such as pain intensity, predict depression, above and beyond the role of
      normative factors, such as positive emotions. The current study characterized the
      independent contributions of pain intensity, pain catastrophizing, and a trait
      measure of happiness to self-rated depressive symptoms. Methods: We recruited and
      enrolled 70 volunteers across 3 groups of participants: two groups of patients
      with current low back pain (one group on opioids and one group opioid-naive), and
      individuals in a methadone maintenance treatment program. Results: Of note,
      participants reporting concurrent opioid use reported significantly higher levels
      of depressive symptomatology, although study groups did not differ on any other
      clinical variables. In our path model, we failed to find direct relationships
      between pain (intensity or duration) and either trait happiness or depressive
      symptoms (p > .05). However, our analysis did reveal that individuals with
      chronic back pain who reported higher levels of trait happiness reported lower
      levels of depressive symptomatology; this effect was significantly mediated by
      lower levels of pain catastrophizing (standardized ab = -.144, p = .002).
      Conclusion: Our analysis suggests that trait happiness, while unrelated to
      ongoing pain, may predict a decreased vulnerability to depressive symptoms in
      individuals with chronic pain, which may operate via lower levels of pain
      catastrophizing.

PMID- 29456449
TI  - International Comparison of Five Herbal Medicine Registration Systems to Inform
      Regulation Development: United Kingdom, Germany, United States of America, United
      Arab Emirates and Kingdom of Bahrain.
AB  - Background: Herbal medicine (HM) regulation is less developed than that of
      allopathic medicines, with some countries lacking specific regulations.
      Objective: For the purpose of informing a registration system for HMs in Kuwait,
      which does not manufacture but imports all HMs, this study compared the
      similarities and differences between the current HM registration systems of five
      countries. Methods: The five countries were selected as major source countries of
      HM in Kuwait (United Kingdom (UK), Germany and United States of America (USA)) or
      because of geographical proximity or size and approach (United Arab Emirates
      (UAE) and Kingdom of Bahrain). Documentary analysis of HM classification systems
      was performed by reviewing the regulatory and law documentation of these
      countries' drug regulatory authority websites. Data on HM definition,
      classification and the main requirements for registration were extracted and
      analysed for similarities and differences. Results: There was diversity in the
      classification of HMs across all five countries including terms used,
      definitions, type of law, requirements, restrictions and preparation type. The
      regulatory authorities of the UK, Germany, UAE  and Kingdom of Bahrain offer
      simplified registration for HMs, where plausible efficacy as a result of
      established traditional use is sufficient. In USA, the concept of traditional use
      does not exist, instead, the product can be categorised as a dietary supplement
      where no assessment or evaluation is required prior to marketing. Conclusions:
      Owing to the inconsistencies in how drug regulatory authorities define HMs, it
      will be important to design a clear definition of what constitutes a HM in
      Kuwait, which is a country that does not produce and register its own products
      but assesses products registered elsewhere.

PMID- 29456450
TI  - Survey on patient safety culture in the Republic of Moldova: a baseline study in
      three healthcare settings.
AB  - Background and aims: The Republic of Moldova is a small ex-soviet country in the
      Central Eastern European group of states, whose official language is Romanian. In
      countries with limited resources, quality improvement in healthcare and patient
      safety are very challenging. This study aims to identify which areas of the
      patient safety culture (PSC) need prompt intervention. Methods: A cross-sectional
      study was conducted in three Moldovan healthcare settings, using the Romanian
      translation of the US Hospital Survey on Patient Safety Culture HSOPSC.
      Descriptive statistics were carried out, based on the responses from n. 929
      staff. Percentages of positive responses (PPRs) by item (41 items) and composite
      (12 PSC areas) were computed. Results: Most respondents were nurses (53%),
      followed by doctors (35%). The main work areas were: primary care (27%), medical
      specialties (20%), gynecology and obstetrics (16%), and general surgery (11%).
      The highest composite PPRs were for: teamwork within units (80%), feedback &
      communication about error, organizational learning-continuous improvement and
      supervisor/manager expectations & actions promoting patient safety (78%), and
      management support for patient safety (75%). The lowest composites were for:
      frequency of events reported (57%), non-punitive response to errors (53%),
      communication openness (51%) and staffing (37%). Conclusion: Our results suggest
      that staffing issues should be tackled to provide safe care. Staff avoid to
      openly report adverse events and/or discuss errors, likely because a poor
      understanding of the potential of these events for learning and because of fear
      of blame or punitive actions. Future research should check psychometrics of the
      Romanian version of the HSOPSC applied to Moldovan staff.

PMID- 29456451
TI  - Human beta-defensin-2 gene transduction of dental pulp cells: A model for pulp
      antimicrobial gene therapy.
AB  - The objective of this study was to determine whether cells from human pulp can be
      transduced to express the antimicrobial peptide--human beta-defensin-2 (HBD-2).
      Primary human pulp cells and gingival fibroblasts from normal tissue, as well as
      two mouse cell lines (NIH 3T3 and AT-84) and a human cell line SCC-9 were
      transduced with a retroviral vector carrying HBD-2 cDNA. ELISA and Northern blot
      analyses were performed to detect HBD-2 expression by these transduced cells.
      Antimicrobail assays using recombinant HBD-2 were performed on two caries
      associated bacteria Streptococcus mutnas and Lactobacillus acidophilus. The
      results showed that transduced pulp cells secreted 62.4 +/- 27.2 ng/3 days of HBD
      2, which was comparable to that by NIH 3T3 (78.0 +/- 14.1 ng/4 days), and higher
      than those by gingival fibroblasts (17.9 +/- 7.9 ng/3 days), AT-84 (2.6 +/- 1.0
      ng/3 days), and SCC-9 (47.6 +/- 9.9 ng/3 days). Northern blot analysis showed
      that the levels of HBD-2 mRNA expression correlated with their protein secretion
      levels. There was approximately 50% reduction of growth when S. mutans and L.
      acidophilus were exposed to HBD-2 at 1 uM. Pulp cells appear to be suitable for
      HBD-2 transduction using retroviral vectors, suggesting a potential for use in
      controlling pulpal infections.

PMID- 29456452
TI  - Factors associated with NO2 and NOX concentration gradients near a highway.
AB  - The objective of this research is to learn how the near-road gradient, in which
      NO2 and NOX (NO + NO2) concentrations are elevated, varies with changes in
      meteorological and traffic variables. Measurements of NO2 and NOX were obtained
      east of I-15 in Las Vegas and fit to functions whose slopes (dCNO2 /dx and dCNOX
      /dx, respectively) characterize the size of the near-road zone where NO2 and NOX
      concentrations from mobile sources on the highway are elevated. These metrics
      were used to learn about the near-road gradient by modeling dCNO2 /dx and dCNOX
      /dx as functions of meteorological variables (e.g., wind direction, wind speed),
      traffic (vehicle count), NOX concentration upwind of the road, and O3
      concentration at two fixed-site ambient monitors. Generalized additive models
      (GAM) were used to model dCNO2 /dx and dCNOX /dx versus the independent variables
      because they allowed for nonlinearity of the variables being compared. When data
      from all wind directions were included in the analysis, variability in O3
      concentration comprised the largest proportion of variability in dCNO2 /dx,
      followed by variability in wind direction. In a second analysis constrained to
      winds from the west, variability in O3 concentration remained the largest
      contributor to variability in dCNO2 /dx, but the relative contribution of
      variability in wind speed to variability in dCNO2 /dx increased relative to its
      contribution for the all-wind analysis. When data from all wind directions were
      analyzed, variability in wind direction was by far the largest contributor to
      variability in dCNOX /dx, with smaller contributions from hour of day and upwind
      NOX concentration. When only winds from the west were analyzed, variability in
      upwind NOX concentration, wind speed, hour of day, and traffic count all were
      associated with variability in dCNOX /dx. Increases in O3 concentration were
      associated with increased magnitude near-road dCNO2 /dx, possibly shrinking the
      zone of elevated concentrations occurring near roads. Wind direction parallel to
      the highway was also related to an increased magnitude of both dCNO2 /dx and
      dCNOX /dx, again likely shrinking the zone of elevated concentrations occurring
      near roads. Wind direction perpendicular to the road decreased the magnitude of
      dCNO2 /dx and dCNOX /dx and likely contributed to growth of the zone of elevated
      concentrations occurring near roads. Thus, variability in near-road
      concentrations is influenced by local meteorology and ambient O3 concentration.

PMID- 29456453
TI  - Exploring the relevance of spatial scale to life cycle inventory results using
      environmentally-extended input-output models of the United States.
AB  - The accuracy of direct and indirect resource use and emissions of products as
      quantified in life cycle models depends in part upon the geographical and
      technological representativeness of the production models. Production conditions
      vary not just between nations, but also within national boundaries. Understanding
      the level of geographic resolution within large industrial nations needed to
      reach acceptable accuracy has not been well-tested across the broad spectrum of
      goods and services consumed. Using an aggregate 15-industryenvironmentally
      extended input-output model of the US along with detailed interstate commodity
      flow data, we test the accuracy of regionalizing the national model into two
      regions (state - rest of US) versus 51 regions (all US states + DC). Our findings
      show the two-region form predicts life cycle emissions and resources used within
      10-20% of the more detailed 51-region form for most of the environmental flows
      studied. The two-region form is less accurate when higher variability exists in
      production conditions for a product.

PMID- 29456454
TI  - Putting trapped populations into place: Climate change and inter-district
      migration flows in Zambia.
AB  - Research shows that the association between adverse climate conditions and human
      migration is heterogeneous. One reason for this heterogeneity is the differential
      vulnerability of populations to climate change. This includes highly vulnerable,
      "trapped" populations that are too poor to migrate given deep and persistent
      poverty, the financial costs of migrating, and the erosion of already fragile
      economic livelihoods under climate change. Another reason for this heterogeneity
      is the differential vulnerability of places. However, despite the growing list of
      studies showing that the climate-migration relationship clearly varies across
      places, there is surprisingly little research on the characteristics of places
      themselves that trap, or immobilize, populations. Accordingly, we provide the
      first account of the "holding power" of places in the association between adverse
      climate conditions and migration flows among 55 districts in Zambia in 2000 and
      2010. Methodologically, we combine high resolution climate information with
      aggregated census micro data to estimate gravity models of inter-district
      migration flows. Results reveal that the association between adverse climate
      conditions and migration is positive only for wealthy migrant-sending districts.
      In contrast, poor districts are characterized by climate-related immobility. Yet,
      our findings show that access to migrant networks enables climate related
      mobility in the poorest districts, suggesting a viable pathway to overcome
      mobility constraints. Planners and policy makers need to recognize the holding
      power of places that can trap populations and develop programs to support in situ
      adaptation and to facilitate migration to avoid humanitarian emergencies.

PMID- 29456455
TI  - Resilient futures of a small island: A participatory approach in Tenerife (Canary
      Islands) to address climate change.
AB  - Adaptation to climate change has been considered to be crucial to current
      societies, especially for small islands. In this paper the case of Tenerife (in
      the Canary Islands) is analysed. Tenerife is a small island located northwest of
      the African continent, in the Atlantic Ocean. Tenerife presents a high
      vulnerability to heatwaves and Saharan dust events as a consequence of its
      closeness to the Saharan desert. In fact, increasing frequency of heatwaves and
      Saharan dust events has been reported and could worsen in the future due to
      global warming. An exploration of adaptation strategies to an increase of the
      frequency and intensity of these phenomena is therefore needed. Different social
      actors have been engaged in a participatory process aiming at exploring pathways
      for adaptation to extreme weather events. Resilience was argued as the relevant
      framing to address those hazards. Four focus group sessions were carried out in
      order to explore key transformative elements necessary to make resilient futures
      for Tenerife. The results highlight the need for broader climate-based policies
      across all sectors to assure that the island becomes resilient to climatic and
      non-climatic shocks.

PMID- 29456456
TI  - Developing and evaluating an instrument to measure Recovery After INtensive care:
      the RAIN instrument.
AB  - Background: Measuring and evaluating patients' recovery, following intensive
      care, is essential for assessing their recovery process. By using a
      questionnaire, which includes spiritual and existential aspects, possibilities
      for identifying appropriate nursing care activities may be facilitated. The study
      describes the development and evaluation of a recovery questionnaire and its
      validity and reliability. Methods: A questionnaire consisting of 30 items on a 5
      point Likert scale was completed by 169 patients (103 men, 66 women), 18 years or
      older (m=69, SD 12.5) at 2, 6, 12 or 24 months following discharge from an ICU.
      An exploratory factor analysis, including a principal component analysis with
      orthogonal varimax rotation, was conducted. Ten initial items, with loadings
      below 0.40, were removed. The internal item/scale structure obtained in the
      principal component analysis was tested in relation to convergent and
      discrimination validity with a multi-trait analysis. Items consistency and
      reliability were assessed by Cronbach's alpha and internal item consistency. Test
      of scale quality, the proportion of missing values and respondents' scoring at
      maximum and minimum levels were also conducted. Results: A total of 20 items in
      six factors - forward looking, supporting relations, existential ruminations,
      revaluation of life, physical and mental strength and need of social support were
      extracted with eigen values above one. Together, they explained 75% of the
      variance. The half-scale criterion showed that the proportion of incomplete scale
      scores ranged from 0% to 4.3%. When testing the scale's ability to differentiate
      between levels of the assessed concept, we found that the observed range of scale
      scores covered the theoretical range. Substantial proportions of respondents, who
      scored at the ceiling for forward looking and supporting relations and at floor
      for the need of social support, were found. These findings should be further
      investigated. Conclusion: The factor analysis, including discriminant validity
      and the mean value for the item correlations, was found to be excellent. The RAIN
      instrument could be used to assess recovery following intensive care. It could
      provide post-ICU clinics and community/primary healthcare nurses with valuable
      information on which areas patients may need more support.

PMID- 29456457
TI  - Effect of ovarian cancer ascites on SKOV-3 cells proteome: new proteins
      associated with aggressive phenotype in epithelial ovarian cancer.
AB  - Background: Epithelial ovarian cancer is the second most lethal gynecological
      cancer worldwide. Ascites can be found in all clinical stages, however in
      advanced disease stages IIIC and IV it is more frequent and could be massive,
      associated with worse prognosis. Due to the above, it was our interest to
      understanding how the ascites of ovarian cancer patients induces the mechanisms
      by which the cells present in it acquire a more aggressive phenotype and to know
      new proteins associated to this process. Methods: A proteomic analysis of SKOV-3
      cells treated with five different EOC ascites was performed by two-dimensional
      electrophoresis coupled to MALDI-TOF. The level of expression of the proteins of
      interest was validated by RT-PCR because several of these proteins have only been
      reported at the messenger level. Results: Among the proteins identified that
      increased their expression in ascites-treated SKOV-3 cells, were Ran GTPase,
      ZNF268, and Synaptotagmin like-3. On the other hand, proteins that were
      negatively regulated by ascites were HLA-I, HSPB1, ARF1, Synaptotagmin 1, and
      hnRNPH1, among others. Furthermore, an interactome for every one of these
      proteins was done in order to identify biological processes, molecular actions,
      and cellular components in which they may participate. Conclusions: Identified
      proteins participate in cellular processes highly relevant to the aggressive
      phenotype such as nuclear transport, regulation of gene expression, vesicular
      trafficking, evasion of the immune response, invasion, metastasis, and in
      resistance to chemotherapy. These proteins may represent a source of information
      which has the potential to be evaluated for the design of therapies directed
      against these malignant cells that reside on ovarian cancer ascites.

PMID- 29456459
TI  - How to Interpret PubMed Queries and Why It Matters.
AB  - A significant fraction of queries in PubMedTM are multiterm queries without
      parsing instructions. Generally, search engines interpret such queries as
      collections of terms, and handle them as a Boolean conjunction of these terms.
      However, analysis of queries in PubMedTM indicates that many such queries are
      meaningful phrases, rather than simple collections of terms. In this study, we
      examine whether or not it makes a difference, in terms of retrieval quality, if
      such queries are interpreted as a phrase or as a conjunction of query terms. And,
      if it does, what is the optimal way of searching with such queries. To address
      the question, we developed an automated retrieval evaluation method, based on
      machine learning techniques, that enables us to evaluate and compare various
      retrieval outcomes. We show that the class of records that contain all the search
      terms, but not the phrase, qualitatively differs from the class of records
      containing the phrase. We also show that the difference is systematic, depending
      on the proximity of query terms to each other within the record. Based on these
      results, one can establish the best retrieval order for the records. Our findings
      are consistent with studies in proximity searching.

PMID- 29456458
TI  - Proteomic identification and characterization of hepatic glyoxalase 1
      dysregulation in non-alcoholic fatty liver disease.
AB  - Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver
      disease worldwide. However, its molecular pathogenesis is incompletely
      characterized and clinical biomarkers remain scarce. The aims of these
      experiments were to identify and characterize liver protein alterations in an
      animal model of early, diet-related, liver injury and to assess novel candidate
      biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein
      fractions from high fat fed apolipoprotein E knockout (ApoE-/-) animals were
      analyzed by quantitative proteomics, utilizing isobaric tags for relative and
      absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem
      mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed
      independently by immunoblotting and immunohistochemistry in both murine tissue
      and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed
      by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results:
      Through proteomic profiling, we identified decreased expression of hepatic
      glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found
      altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments
      demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first
      hyperacetylated then ubiquitinated and degraded, leading to an increase in
      reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients,
      increased serum levels of the primary methylglyoxal-derived advanced glycation
      endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass
      index (r = 0.520, p < 0.0001). Conclusion: Collectively these results demonstrate
      the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination
      degradation pathway as the functional mechanism. Further investigation of the
      role of GLO1 in the molecular pathogenesis of NAFLD is warranted.

PMID- 29456460
TI  - The Hamming Ball Sampler.
AB  - We introduce the Hamming ball sampler, a novel Markov chain Monte Carlo
      algorithm, for efficient inference in statistical models involving high
      dimensional discrete state spaces. The sampling scheme uses an auxiliary variable
      construction that adaptively truncates the model space allowing iterative
      exploration of the full model space. The approach generalizes conventional Gibbs
      sampling schemes for discrete spaces and provides an intuitive means for user
      controlled balance between statistical efficiency and computational tractability.
      We illustrate the generic utility of our sampling algorithm through application
      to a range of statistical models. Supplementary materials for this article are
      available online.

PMID- 29456461
TI  - Factors Associated with Money Mismanagement Among Adults with Severe Mental
      Illness and Substance Abuse.
AB  - People with severe mental illness often have substantial problems with money
      mismanagement such as losing or lending money to other people and making
      impulsive or unnecessary purchases, including drugs and alcohol. Money
      mismanagement in turn affects patients' health and social functioning, and can
      lead to homelessness and other harm. This cross-sectional study evaluated
      demographic and clinical predictors of money mismanagement among SSI/SSDI
      recipients. SSI/SSDI beneficiaries (N = 95) with recent cocaine use initiating a
      clinical trial were assessed at intake with demographic, cognitive, psychiatric,
      social/family, substance abuse, and financial measures. In multivariate
      regression analyses, psychiatric functioning and drug dependence diagnosis were
      independent predictors of self-reported money mismanagement. Even within
      individuals whom all had recently used cocaine, those with drug dependence and
      those with more psychiatric symptomatology had more difficulty managing their
      funds. Future studies might determine whether people who reduce their drug use
      and psychiatric symptomatology go on to better manage their funds.

PMID- 29456462
TI  - Taking Sides in E-cigarette Research.
AB  - In the last ten years, an eclectic mix of electronic nicotine delivery products
      ('e-cigarettes') and practices have proliferated in the US with little
      restriction, producing a vast array of vaping mechanisms, flavors, and styles. At
      the same time, anti-tobacco movements have targeted e-cigarettes as a threat to
      public health and advocated for restricting e-cigarettes in much the same way as
      conventional cigarettes. While anti-vaping proponents associated with public
      health movements have typically regarded e-cigarettes as primarily harmful
      products that should be suppressed, vaping advocates regard e-cigarettes as harm
      reduction products that should be readily accessible to smokers. Distrust between
      these two warring "sides" animates the controversy over e-cigarettes. In our role
      as researchers conducting a qualitative study on e-cigarette use, we encountered
      suspicion and anger from members of an e-cigarette forum who felt that pro-vaping
      perspectives were often misrepresented by researchers. As a result, we dropped
      our initial plan to host a group discussion of questions directly related to our
      study on the forum. Nevertheless, the incident illuminated how vaping advocates
      have resisted dominant narratives regarding tobacco and nicotine use,
      destabilized nicotine product categories and challenged interpretations of
      nicotine use that dichotomize pleasure and health.

PMID- 29456463
TI  - Income and Child Maltreatment in Unmarried Families: Evidence from the Earned
      Income Tax Credit.
AB  - This study estimates the associations of income with both (self-reported) child
      protective services (CPS) involvement and parenting behaviors that proxy for
      child abuse and neglect risk among unmarried families. Our primary strategy
      follows the instrumental variables (IV) approach employed by Dahl and Lochner
      (2012), which leverages variation between states and over time in the generosity
      of the total state and federal Earned Income Tax Credit for which a family is
      eligible to identify exogenous variation in family income. As a robustness check,
      we also estimate standard OLS regressions (linear probability models), reduced
      form OLS regressions, and OLS regressions with the inclusion of a control
      function (each with and without family-specific fixed effects). Our micro-level
      data are drawn from the Fragile Families and Child Wellbeing Study, a
      longitudinal birth-cohort of relatively disadvantaged urban children who have
      been followed from birth to age nine. Results suggest that an exogenous increase
      in income is associated with reductions in behaviorally-approximated child
      neglect and CPS involvement, particularly among low-income single-mother
      families.

PMID- 29456464
TI  - Three-Dimensional Multiscale, Multistable, and Geometrically Diverse
      Microstructures with Tunable Vibrational Dynamics Assembled by Compressive
      Buckling.
AB  - Microelectromechanical systems remain an area of significant interest in
      fundamental and applied research due to their wide ranging applications. Most
      device designs, however, are largely two-dimensional and constrained to only a
      few simple geometries. Achieving tunable resonant frequencies or broad
      operational bandwidths requires complex components and/or fabrication processes.
      The work presented here reports unusual classes of three-dimensional (3D)
      micromechanical systems in the form of vibratory platforms assembled by
      controlled compressive buckling. Such 3D structures can be fabricated across a
      broad range of length scales and from various materials, including soft polymers,
      monocrystalline silicon, and their composites, resulting in a wide scope of
      achievable resonant frequencies and mechanical behaviors. Platforms designed with
      multistable mechanical responses and vibrationally de-coupled constituent
      elements offer improved bandwidth and frequency tunability. Furthermore, the
      resonant frequencies can be controlled through deformations of an underlying
      elastomeric substrate. Systematic experimental and computational studies include
      structures with diverse geometries, ranging from tables, cages, rings, ring
      crosses, ring-disks, two-floor ribbons, flowers, umbrellas, triple-cantilever
      platforms, and asymmetric circular helices, to multilayer constructions. These
      ideas form the foundations for engineering designs that complement those
      supported by conventional, microelectromechanical systems, with capabilities that
      could be useful in systems for biosensing, energy harvesting and others.

PMID- 29456465
TI  - Barrmaelia and Entosordaria in Barrmaeliaceae (fam. nov., Xylariales) and
      critical notes on Anthostomella -like genera based on multigene phylogenies.
AB  - Phylogenetic analyses of a combined DNA data matrix containing ITS, LSU, rpb2 and
      tub2 sequences of representative Xylariales revealed that the genus Barrmaelia is
      a well-defined monophylum, as based on four of its described species (B.
      macrospora, B. moravica, B. oxyacanthae, B. rhamnicola) and the new species B.
      rappazii. The generic type of Entosordaria, E. perfidiosa, is revealed as the
      closest relative of Barrmaelia, being phylogenetically distant from the generic
      type of Clypeosphaeria, C. mamillana, which belongs to Xylariaceae sensu stricto.
      Entosordaria and Barrmaelia are highly supported and form a distinct lineage,
      which is recognised as the new family Barrmaeliaceae. The new species E. quercina
      is described. Barrmaelia macrospora, B. moravica and B. rhamnicola are
      epitypified and E. perfidiosa is lecto- and epitypified. Published sequences of
      Anthostomella and several Anthostomella-like species from the genera
      Alloanthostomella, Anthostomelloides, Neoanthostomella, Pseudoanthostomella and
      Pyriformiascoma are evaluated, demonstrating the necessity of critical inspection
      of published sequence data before inclusion in phylogenies. Verified isolates of
      several species from these genera should be re-sequenced to affirm their
      phylogenetic affinities. In addition, the generic type of Anthostomella should be
      sequenced before additional generic re-arrangements are proposed.

PMID- 29456466
TI  - Mastectomy - Current Challenges and Questions.

PMID- 29456467
TI  - Clinical Approaches to Breast Reconstruction: What Is the Appropriate
      Reconstructive Procedure for My Patient?
AB  - Breast reconstruction after breast cancer is an emotional subject for women.
      Consequently, the correct timing and surgical procedure for each individual woman
      are important. In general, heterologous or autologous reconstructive procedures
      are available, both having advantages and disadvantages. Breast size, patient
      habitus, and previous surgeries or radiation therapy need to be considered,
      independent of the chosen procedure. New surgical techniques, refinement of
      surgical procedures, and the development of supportive materials have increased
      the general patient collective eligible for breast reconstruction. This review
      highlights the different approaches to immediate breast reconstruction using
      autologous or heterologous techniques.

PMID- 29456468
TI  - Psychosocial Aspects of Immediate versus Delayed Breast Reconstruction.
AB  - Background: Only little is known about the psychosocial aspects of breast cancer
      patients after mastectomy with immediate versus delayed breast reconstruction.
      Methods: We systematically screened PubMed using the following key words:
      mastectomy, immediate vs. delayed reconstruction, psychosocial aspects and
      quality of life. To highlight different psychological outcomes, studies were
      categorized into those describing: anxiety, depression, body image and
      satisfaction with the surgical outcome. We also compared patients after
      mastectomy alone with those undergoing immediate or delayed reconstruction.
      Results: Methodologies and psychological outcomes varied among the identified
      studies, making it difficult to compare results. There are contradictory outcomes
      concerning the psychosocial aspects of breast cancer patients after mastectomy
      alone compared with those who underwent an immediate or delayed reconstruction
      following mastectomy. Some studies show that immediate reconstruction after
      mastectomy had a positive impact on patients' psychological well-being. In
      contrast, other studies indicated that in the long-term view the compared patient
      groups were very similar concerning psychosocial aspects. Conclusion: Analyzing
      different aspects of psychosocial well-being after breast cancer surgery, there
      might be an advantage in choosing immediate reconstruction, if oncological safety
      allows it.

PMID- 29456469
TI  - Prophylactic Surgery: For Whom, When and How?
AB  - Risk-reducing surgery has proved to be a reasonable procedure in healthy women
      with a definitely elevated risk of developing cancer. Here we consider the
      elevated risk of breast and ovarian cancer. There is a clear indication for such
      surgery in healthy women with a pathogenic BRCA1/2 mutation. For these patients,
      a risk-reducing bilateral mastectomy leads to a verifiable reduction in mortality
      from breast cancer, particularly for young patients. In most cases, surgery is
      combined with breast reconstruction. The pros and cons of surgical treatment and
      the different surgical techniques have to be explained to and carefully
      considered with the patient. As yet, no unequivocal data for the benefits of
      intensifying early detection have been ascertained with respect to mortality from
      breast carcinoma. In index patients with a BRCA mutation, the surgical treatment
      should depend on the prognosis of the primary disease. A lower age at onset and a
      better prognosis of the primary disease make a contralateral mastectomy (CPM)
      more reasonable. In the case of BRCA mutation-related cancer, a reduction of
      mortality through CPM has been proven. A risk-reducing adnexectomy is basically
      recommended for BRCA mutation carriers. Healthy premenopausal women need a
      subsequent hormone replacement therapy. The prognosis of the patients is
      dominated by the ovarian carcinoma. This can be prevented by risk-reducing
      salpingo-oophorectomy in 95% of the cases.

PMID- 29456470
TI  - Is Mastectomy Oncologically Safer than Breast-Conserving Treatment in Early
      Breast Cancer?
AB  - Aim: To describe and discuss the evidence for oncological safety of different
      procedures in oncological breast surgery, i.e. breast-conserving treatment versus
      mastectomy. Methods: Literature review and discussion. Results: Oncological
      safety in breast cancer surgery has many dimensions. Breast-conserving treatment
      has been established as the standard surgical procedure for primary breast cancer
      and fits to the preferences of most breast cancer patients concerning oncological
      safety and aesthetic outcome. Conclusions: Breast-conserving treatment is safe.
      Nonetheless, the preferences of the individual patients in their consideration of
      breast conservation versus mastectomy should be integrated into routine treatment
      decisions.

PMID- 29456471
TI  - Neoadjuvant Chemotherapy Exerts Selection Pressure Towards Luminal Phenotype
      Breast Cancer.
AB  - Background: Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has
      not been extensively described and few data exist on whether expression of the
      primary tumor hormone receptors, HER2 and Ki-67 changes as a result of
      chemotherapy. Materials and Methods: We analyzed specimens from all BC patients
      treated with anthracycline/taxane-based NAC at our Institution between January
      2010 and March 2015 (n = 325). The expression of estrogen receptor (ER),
      progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC
      specimens. McNemar's test was used to compare paired proportions. Results: Among
      patients with residual disease after NAC, basal phenotype was luminal A, luminal
      B, HER2 positive and triple negative in 44, 111, 74 and 27 cases, respectively.
      PR-positive tumors decreased from 68.0% in the initial biopsy sample to 61.7% in
      the surgical specimen (p = 0.024). A Ki-67 of < 20% increased from 23.6% to 45%
      (p < 0.001). ER expression changed from positive to negative in 5% and from
      negative to positive in 16.7% of cases. Overall, 30% of cases underwent subtype
      changes, 79% of them towards luminal differentiation. Conclusions: The switch
      towards luminal phenotype suggests some kind of endocrine effect of NAC. Our
      findings raise renewed interest in combinatorial cytotoxic chemotherapy with
      concomitant or rather sequential endocrine therapy, either alone or with targeted
      agents.

PMID- 29456472
TI  - Electron Beam Intraoperative Radiotherapy (ELIOT) in Pregnant Women with Breast
      Cancer: From in Vivo Dosimetry to Clinical Practice.
AB  - Background: The aim of this study was to confirm our preliminary results with in
      vivo dosimetry in non-pregnant breast cancer patients receiving electron beam
      intraoperative radiotherapy (ELIOT) and to report on the first treatment in a
      pregnant woman. Patients and Methods: Following our previous experience, 5 non
      pregnant patients receiving ELIOT to the tumor bed after breast-conserving
      surgery (BCS) were studied with thermoluminescent dosimeters positioned in the
      subdiaphragmatic region, within the uterus, and in the ovarian region. In
      December 2011, the first pregnant breast cancer patient underwent BCS and ELIOT
      (21 Gy at 90% isodose) during the 15th week of gestation. Results: The mean dose
      to the subdiaphragmatic external region in the 5 non-pregnant patients was 5.57
      mGy, while pelvic measurements were below 1 mGy. The actual dosimetry of the
      pregnant patient showed a mean subdiaphragmatic dose of 4.34 mGy, a mean
      suprapubic dose of 1.64 mGy, and mean ovarian doses of 1.48 mGy (right-sided) and
      1.44 mGy (left-sided). The expected dose to the fetus was estimated as 0.84 mGy
      (0.004% of the prescribed dose). Conclusion: ELIOT as an anticipated boost to the
      breast could be considered in pregnant women in the early second trimester,
      postponing whole-breast irradiation after delivery.

PMID- 29456473
TI  - Adverse Events of Trastuzumab Emtansine (T-DM1) in the Treatment of HER2-Positive
      Breast Cancer Patients.
AB  - The human epidermal growth factor receptor 2 (HER2) is commonly associated with
      poor prognosis and is overexpressed in approximately 15-20% of all breast
      cancers. The introduction of HER2-targeted therapies led to significant
      improvement in the prognosis of patients with HER2-positive breast cancer, for
      both early and advanced disease. These targeted therapies include the antibodies
      trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the
      antibody-drug conjugate trastuzumab emtansine (T-DM1). T-DM1 combines the anti
      tumor activity of trastuzumab with that of DM1, a highly potent derivative of the
      anti-microtubule agent maytansine, resulting in increased anti-tumor activity.
      Notably, this agent has been demonstrated to be safe and is associated with low
      toxicity rates. However, maytansinoid, the cytotoxic component of T-DM1, does
      have the potential to induce various adverse events, particularly radiation
      necrosis, when used in combination with stereotactic radiosurgery. In this
      review, we aimed to summarize the current literature regarding T-DM1 safety and
      toxicity, with special emphasis on the existing landmark studies.

PMID- 29456474
TI  - Electrochemotherapy in Breast Cancer - Discussion of the Method and Literature
      Review.
AB  - Breast cancer is the most common cause of skin metastases in women. The
      probability of their occurrence ranges from about 5% in the entire population to
      as much as 30% in the late stages of the disease. Although rarely life
      threatening, they have a major impact on the quality of life of patients with
      this diagnosis, being the cause of pain, effusion, ulceration, infection, and
      psychological discomfort. Available methods of treatment, both local and
      systemic, often fail to provide adequate control of the disease. A particular
      challenge seems to be the treatment of those patients with cutaneous metastases
      who, due to the extent of their metastases, are not eligible for resection, in
      whom the possibility of radiation therapy has already been used, and in whom
      systemic therapy is ineffective or contraindicated. A new method providing the
      opportunity for effective treatment is electrochemotherapy (ECT). ECT combines
      electropulsation of tumor cells (by local application of electric pulses) and
      administration of antineoplastic drugs such as cisplatin or bleomycin (either
      intravenous or intratumoral). Several clinical studies have demonstrated that ECT
      provides safe, efficient, and non-invasive locoregional treatment for chest wall
      breast cancer recurrence.

PMID- 29456475
TI  - Highlights from ABC4 - Bridging the Gap.

PMID- 29456476
TI  - Scratching the Surface of Werner Syndrome and Human Ageing.

PMID- 29456477
TI  - Dual Diagnosis of Ellis-van Creveld Syndrome and Hearing Loss in a Consanguineous
      Family.
AB  - Multilocus analysis of rare or genetically heterogeneous diseases is a distinct
      advantage of next-generation sequencing (NGS) over conventional single-gene
      investigations. Recent studies have begun to uncover an under-recognized
      prevalence of dual molecular diagnoses in patients with a "blended" phenotype
      that is the result of 2 clinical diagnoses involving 2 separate genetic loci.
      This blended phenotype could be mistakenly interpreted as a novel clinical
      extension of a single-gene disorder. In this study, we ascertained a proband from
      a large consanguineous Iranian family who manifests postlingual, progressive,
      moderate hearing loss in addition to suspected Ellis-van Creveld syndrome
      phenotype. NGS with a customized skeletal dysplasia panel containing over 370
      genes and subsequent bioinformatics analysis disclosed 2 homozygous mutations in
      EVC2 (c.2653C>T; p.Arg885*) and COL11A2 (c.966dup; p.Thr323Hisfs*19),
      respectively. This study highlights a dual molecular diagnosis in a patient with
      a blending of 2 distinct phenotypes and illustrates the advantage and importance
      of this staple technology to facilitate rapid and comprehensive genetic
      dissection of a heterogeneous phenotype. The differentiation between phenotypic
      expansion of a genetic disorder and a blended phenotype that is due to more than
      one distinct genetic aberration is essential in order to reduce the diagnostic
      odyssey endured by patients.

PMID- 29456478
TI  - Proximal Deletion of 6q Overlapping with Toriello-Carey Facial Phenotype:
      Prenatal Findings, Clinical Course, Differential Diagnosis, and Review.
AB  - Proximal deletion of 6q is a relatively rare chromosomal abnormality. Reported
      patients have deletions of different sizes but share partial overlap and present
      with similar clinical features, and some of them were described prior to the
      introduction of chromosome microarrays. We describe a male patient with prenatal
      sonographic findings of nuchal edema, intrauterine growth restriction, renal
      pelvis dilatation, and oligohydramnios. At birth, facial dysmorphism,
      retro/micrognathia, a short and wide neck as well as cardiovascular and renal
      anomalies were noted. His clinical evolution has been marked by failure to
      thrive, severe developmental delay, and cognitive impairment. The diagnosis of
      Toriello-Carey syndrome (TCS) was based on his "gestalt." aCGH identified a de
      novo proximal deletion of 17 Mb in 6q (6q12q14.3). Deletion 6q13q14 seems to be
      responsible for the main facial features and should be considered within the
      differential diagnosis of TCS.

PMID- 29456479
TI  - A Novel Missense Variant in the PVRL4 Gene Underlying Ectodermal Dysplasia
      Syndactyly Syndrome in a Turkish Child.
AB  - Ectodermal dysplasia-syndactyly syndrome is a rare autosomal recessive congenital
      disorder caused by mutations in PVRL4 coding for nectin-4. Five different
      mutations in the PVRL4 gene, including 3 homozygous missense mutations, have been
      reported. Here, we present an unreported missense variant (c.247C>T, p.His83Tyr)
      in a consanguineous Turkish family.

PMID- 29456480
TI  - Novel Homozygous Missense Mutation in RYR1 Leads to Severe Congenital Ptosis,
      Ophthalmoplegia, and Scoliosis in the Absence of Myopathy.
AB  - Ryanodine receptor 1 (RYR1) is an intracellular calcium receptor primarily
      expressed in skeletal muscle with a role in excitation contraction. Both dominant
      and recessive mutations in the RYR1 gene cause a range of RYR1-related myopathies
      and/or susceptibility to malignant hyperthermia (MH). Recently, an atypical
      manifestation of ptosis, variably presenting with ophthalmoplegia, facial
      paralysis, and scoliosis but without significant muscle weakness, has been
      reported in 9 cases from 4 families with bialleic variants in RYR1. Two affected
      children from a consanguineous family with severe congenital ptosis,
      ophthalmoplegia, scoliosis, and distinctive long faces but without skeletal
      myopathy were studied. To identify the cause of the hereditary condition, DNA
      from the proband was subjected to whole exome sequencing (WES). WES revealed a
      novel homozygous missense variant in RYR1 (c.14066T>A; p.IIe4689Asn), which
      segregated within the family. Although the phenotype of the affected siblings in
      this study was similar to previously described cases, the clinical features were
      more severely expressed. Our findings contribute to the expansion of phenotypes
      related to RYR1 dysfunction. Additionally, it supports a new RYR1-related
      clinical presentation without musculoskeletal involvement. It is important that
      individuals with RYR1 mutations are considered susceptible to MH, as 70% of the
      MH cases are caused by mutations in the RYR1 gene.

PMID- 29456481
TI  - Double Interstitial Deletion of the Long Arm of Chromosome 6 in a Patient with
      Pierre Robin Sequence, Dysmorphisms, and Severe Developmental Delay.
AB  - Reported here is the case of a 1.8-year-old boy with a 9.6- Mb deletion in
      6q13q14.1 and an 11.2-Mb deletion in 6q21q22.31, ascertained through array CGH,
      as the result of a complex de novo chromosome rearrangement. The clinical picture
      of this patient is characterized by severe psychomotor delay, dysmorphic
      features, and some congenital defects. Although, as reported in the literature,
      phenotypes associated with 6q deletions may vary, an attempt was made to
      associate the patient's symptoms to either deletion, comparing them to previously
      reported cases. Only a limited specific correlation was found, probably due to
      the prevalence of very common symptoms.

PMID- 29456482
TI  - Ring Chromosome 17 Not Involving the Miller-Dieker Region: A Case with Drug
      Resistant Epilepsy.
AB  - Chromosomal abnormalities are often identified in people with neurodevelopmental
      disorders including intellectual disability, autism, and epilepsy. Ring
      chromosomes, which usually involve gene copy number loss, are formed by fusion of
      subtelomeric or telomeric chromosomal regions. Some ring chromosomes, including
      ring 14, 17, and 20, are strongly associated with seizure disorders. We report an
      individual with a ring chromosome 17, r(17)(p13.3q25.3), with a terminal 17q25.3
      deletion and no short arm copy number loss, and with a phenotype characterized by
      intellectual disability and drug-resistant epilepsy, including a propensity for
      nonconvulsive status epilepticus.

PMID- 29456483
TI  - Two Novel Pathogenic MID1 Variants and Genotype-Phenotype Correlation Reanalysis
      in X-Linked Opitz G/BBB Syndrome.
AB  - X-linked Opitz G/BBB syndrome (XLOS) is a multisystemic congenital condition,
      caused by mutations in the midline-1 gene (MID1), characterized by a large inter-
      and intrafamilial phenotypic variability and often associated with intellectual
      disability (ID). We report clinical, genetic, and molecular findings in 4
      patients with typical XLOS dysmorphic features belonging to 2 unrelated families.
      Two novel pathogenic loss-of-function MID1 variants, a maternally inherited
      c.1656del and a de novo c.1215_1228dup, were identified. Subsequently, we
      performed a genotype-phenotype analysis using data from 91 male XLOS patients. To
      test the mutation impact on the phenotype; the type of mutation, the MID1
      impaired domain and function were compared with the presence of each of the major
      clinical features (hypertelorism, clefts of the lip and/or palate, laryngo
      tracheo-esophageal abnormalities, hypospadias and ID) and minor clinical features
      (brain, heart, and anal defects). No statistically significant correlation was
      found with these features. Further investigations, as well as exhaustive and
      unequivocal phenotyping, may be required to improve our knowledge of the
      biological mechanisms underlying this syndrome and to provide more adequate
      disease management.

PMID- 29456484
TI  - 7q Deletion/12q Duplication Is the Possible Cause of an Alobar Holoprosencephaly
      Case.
AB  - Holoprosencephaly (HPE) spectrum disorder is the most common congenital
      malformation of the human brain with absence of or incomplete midline cleavage.
      Its cause is heterogenic, making genetic counseling a challenge. In this case
      report, a pregnancy affected by alobar HPE is described. Using aCGH, an 8.9-Mb
      deletion at 7q36.1q36.3 together with a 4.9-Mb duplication at 12q24.32q24.33 is
      assumed to be the possible reason for this alobar HPE case. It is discussed that
      disruption of key elements of the developing brain, taking environmental factors
      into account, contributes to the HPE spectrum. The use of aCGH for invasive
      prenatal testing is starting to become the standard technique, providing accurate
      information about the cause of congenital diseases for couples receiving genetic
      counseling.

PMID- 29456485
TI  - Effect of Spatial Smoothing on Task fMRI ICA and Functional Connectivity.
AB  - Spatial smoothing is a widely used preprocessing step in functional magnetic
      resonance imaging (fMRI) data analysis. In this work, we report on the spatial
      smoothing effect on task-evoked fMRI brain functional mapping and functional
      connectivity. Initially, we decomposed the task fMRI data into a collection of
      components or networks by independent component analysis (ICA). The designed task
      paradigm helps identify task-modulated ICA components (highly correlated with the
      task stimuli). For the ICA-extracted primary task component, we then measured the
      task activation volume at the task response foci. We used the task timecourse
      (designed) as a reference to order the ICA components according to the task
      correlations of the ICA timecourses. With the re-ordered ICA components, we
      calculated the inter-component function connectivity (FC) matrix (correlations
      among the ICA timecourses). By repeating the spatial smoothing of fMRI data with
      a Gaussian smoothing kernel with a full width at half maximum (FWHM) of {1, 3, 6,
      9, 12, 15, 20, 25, 30, 35} mm, we measured the spatial smoothing effects. Our
      results show spatial smoothing reveals the following effects: (1) It decreases
      the task extraction performance of single-subject ICA more than that of multi
      subject ICA; (2) It increases the task volume of multi-subject ICA more than that
      of single-subject ICA; (3) It strengthens the functional connectivity of single
      subject ICA more than that of multi-subject ICA; and (4) It impacts the positive
      negative imbalance of single-subject ICA more than that of multi-subject ICA. Our
      experimental results suggest a 2~3 voxel FWHM spatial smoothing for single
      subject ICA in achieving an optimal balance of functional connectivity, and a
      wide range (2~5 voxels) of FWHM for multi-subject ICA.

PMID- 29456486
TI  - Generic HRTFs May be Good Enough in Virtual Reality. Improving Source
      Localization through Cross-Modal Plasticity.
AB  - Auditory spatial localization in humans is performed using a combination of
      interaural time differences, interaural level differences, as well as spectral
      cues provided by the geometry of the ear. To render spatialized sounds within a
      virtual reality (VR) headset, either individualized or generic Head Related
      Transfer Functions (HRTFs) are usually employed. The former require arduous
      calibrations, but enable accurate auditory source localization, which may lead to
      a heightened sense of presence within VR. The latter obviate the need for
      individualized calibrations, but result in less accurate auditory source
      localization. Previous research on auditory source localization in the real world
      suggests that our representation of acoustic space is highly plastic. In light of
      these findings, we investigated whether auditory source localization could be
      improved for users of generic HRTFs via cross-modal learning. The results show
      that pairing a dynamic auditory stimulus, with a spatio-temporally aligned visual
      counterpart, enabled users of generic HRTFs to improve subsequent auditory source
      localization. Exposure to the auditory stimulus alone or to asynchronous
      audiovisual stimuli did not improve auditory source localization. These findings
      have important implications for human perception as well as the development of VR
      systems as they indicate that generic HRTFs may be enough to enable good auditory
      source localization in VR.

PMID- 29456487
TI  - The Discontinuous Galerkin Finite Element Method for Solving the MEG and the
      Combined MEG/EEG Forward Problem.
AB  - In Electro- (EEG) and Magnetoencephalography (MEG), one important requirement of
      source reconstruction is the forward model. The continuous Galerkin finite
      element method (CG-FEM) has become one of the dominant approaches for solving the
      forward problem over the last decades. Recently, a discontinuous Galerkin FEM (DG
      FEM) EEG forward approach has been proposed as an alternative to CG-FEM (Engwer
      et al., 2017). It was shown that DG-FEM preserves the property of conservation of
      charge and that it can, in certain situations such as the so-called skull
      leakages, be superior to the standard CG-FEM approach. In this paper, we
      developed, implemented, and evaluated two DG-FEM approaches for the MEG forward
      problem, namely a conservative and a non-conservative one. The subtraction
      approach was used as source model. The validation and evaluation work was done in
      statistical investigations in multi-layer homogeneous sphere models, where an
      analytic solution exists, and in a six-compartment realistically shaped head
      volume conductor model. In agreement with the theory, the conservative DG-FEM
      approach was found to be superior to the non-conservative DG-FEM implementation.
      This approach also showed convergence with increasing resolution of the
      hexahedral meshes. While in the EEG case, in presence of skull leakages, DG-FEM
      outperformed CG-FEM, in MEG, DG-FEM achieved similar numerical errors as the CG
      FEM approach, i.e., skull leakages do not play a role for the MEG modality. In
      particular, for the finest mesh resolution of 1 mm sources with a distance of
      1.59 mm from the brain-CSF surface, DG-FEM yielded mean topographical errors
      (relative difference measure, RDM%) of 1.5% and mean magnitude errors (MAG%) of
      0.1% for the magnetic field. However, if the goal is a combined source analysis
      of EEG and MEG data, then it is highly desirable to employ the same forward model
      for both EEG and MEG data. Based on these results, we conclude that the newly
      presented conservative DG-FEM can at least complement and in some scenarios even
      outperform the established CG-FEM approaches in EEG or combined MEG/EEG source
      analysis scenarios, which motivates a further evaluation of DG-FEM for
      applications in bioelectromagnetism.

PMID- 29456488
TI  - Exploring the Complexity of Cortical Development Using Single-Cell
      Transcriptomics.
AB  - The developing neocortex in the mammalian brain is composed of multiple cell
      types including apical progenitors (AP), basal progenitors (BP), and neurons that
      populate three different layers, the ventricular zone (VZ), the subventricular
      zone (SVZ), and the cortical plate (CP). Despite recent advances, the diversity
      of the existing cell populations including those which are differentiating and
      mature, their biogenesis and the underlying gene regulatory mechanisms remain
      poorly known. Recent studies have taken advantage of the rapidly emerging single
      cell technologies to decode the heterogeneity of cell populations at the
      transcriptome level during cortical development and their molecular details. Here
      we review these studies and provide an overview of the steps in single-cell
      transcriptomics including both experimental and computational analysis. We also
      discuss how single-cell genomics holds a big potential in future for brain
      research and discuss its possible applications and biological insights that can
      be achieved from these approaches. We conclude this review by discussing the
      current challenges in the implementation of single-cell techniques toward a
      comprehensive understanding of the genetic and epigenetic mechanisms underlying
      neocortex development.

PMID- 29456489
TI  - Hurst Exponent Analysis of Resting-State fMRI Signal Complexity across the Adult
      Lifespan.
AB  - Exploring functional information among various brain regions across time enables
      understanding of healthy aging process and holds great promise for age-related
      brain disease diagnosis. This paper proposed a method to explore fractal
      complexity of the resting-state functional magnetic resonance imaging (rs-fMRI)
      signal in the human brain across the adult lifespan using Hurst exponent (HE). We
      took advantage of the examined rs-fMRI data from 116 adults 19 to 85 years of age
      (44.3 +/- 19.4 years, 49 females) from NKI/Rockland sample. Region-wise and voxel
      wise analyses were performed to investigate the effects of age, gender, and their
      interaction on complexity. In region-wise analysis, we found that the healthy
      aging is accompanied by a loss of complexity in frontal and parietal lobe and
      increased complexity in insula, limbic, and temporal lobe. Meanwhile, differences
      in HE between genders were found to be significant in parietal lobe (p = 0.04,
      corrected). However, there was no interaction between gender and age. In voxel
      wise analysis, the significant complexity decrease with aging was found in
      frontal and parietal lobe, and complexity increase was found in insula, limbic
      lobe, occipital lobe, and temporal lobe with aging. Meanwhile, differences in HE
      between genders were found to be significant in frontal, parietal, and limbic
      lobe. Furthermore, we found age and sex interaction in right parahippocampal
      gyrus (p = 0.04, corrected). Our findings reveal HE variations of the rs-fMRI
      signal across the human adult lifespan and show that HE may serve as a new
      parameter to assess healthy aging process.

PMID- 29456491
TI  - Synaptic E-I Balance Underlies Efficient Neural Coding.
AB  - Both theoretical and experimental evidence indicate that synaptic excitation and
      inhibition in the cerebral cortex are well-balanced during the resting state and
      sensory processing. Here, we briefly summarize the evidence for how neural
      circuits are adjusted to achieve this balance. Then, we discuss how such
      excitatory and inhibitory balance shapes stimulus representation and information
      propagation, two basic functions of neural coding. We also point out the benefit
      of adopting such a balance during neural coding. We conclude that excitatory and
      inhibitory balance may be a fundamental mechanism underlying efficient coding.

PMID- 29456490
TI  - Limited Access to a High Fat Diet Alters Endocannabinoid Tone in Female Rats.
AB  - Emerging evidence suggest an impaired endocannabinoid activity in the
      pathophysiology of binge eating disorder (BED). Herein, we investigated whether
      endocannabinoid tone could be modified as a consequence of dietary-induced binge
      eating in female rats. For this purpose, brain levels of the endocannabinoids
      anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), as well as two
      endocannabinoid-like lipids, oleoylethanolamide (OEA) and palmitoylethanolamide
      (PEA), were assessed in different brain areas involved in the hedonic feeding
      (i.e., prefrontal cortex, nucleus accumbens, amygdala, hippocampus, and
      hypothalamus). The brain density of cannabinoid type-1 receptors (CB1) was also
      evaluated. Furthermore, we determined plasma levels of leptin, ghrelin, and
      corticosterone hormones, which are well-known to control the levels of
      endocannabioids and/or CB1 receptors in the brain. To induce binge eating
      behavior, rats were subject to an intermittent and limited access to a high fat
      diet (HFD) (margarine). Three experimental groups were used, all with ad libitum
      access to chow: control (CTRL), with no access to margarine; low restriction
      (LR), with 2 h margarine access 7 days/week; high restriction (HR), with 2 h
      margarine access 3 days/week. Bingeing was established when margarine intake in
      the HR group exceeded that of the LR group. Our results show that, compared to
      CTRL, AEA significantly decreased in the caudate putamen, amygdala, and
      hippocampus of HR group. In contrast, 2-AG significantly increased in the
      hippocampus while OEA decreased in the hypothalamus. Similar to the HR group, AEA
      and OEA decreased respectively in the amygdala and hypothalamus and 2-AG
      increased in the hippocampus of LR group. Moreover, LR group also had AEA
      decreased in the prefrontal cortex and increased in the nucleus accumbens. In
      both groups we found the same reduction of CB1 receptor density in the prefrontal
      cortex compared to CTRL. Also, LR and HR groups showed alterations in both
      ghrelin and corticosterone levels, while leptin remained unaltered. In
      conclusion, our findings show a modified endocannabinoid tone due to margarine
      exposure, in several brain areas that are known to influence the hedonic aspect
      of food. Even if not uniquely specific to binge eating, margarine-induced changes
      in endocannabinoid tone could contributes to the development and maintenance of
      this behavior.

PMID- 29456492
TI  - Novel pH-Sensitive Lipid Based Exo-Endocytosis Tracers Reveal Fast Intermixing of
      Synaptic Vesicle Pools.
AB  - Styryl dyes and genetically encoded pH-sensitive fluorescent proteins like
      pHluorin are well-established tools for the optical analysis of synaptic vesicle
      (SV) recycling at presynaptic boutons. Here, we describe the development of a new
      class of fluorescent probes based on pH-sensitive organic dyes covalently bound
      to lipids, providing a promising complementary assay to genetically encoded
      fluorescent probes. These new optical tracers allow a pure read out of membrane
      turnover during synaptic activity and visualization of multiple rounds of
      stimulation-dependent SV recycling without genetic perturbation. Measuring the
      incorporation efficacy of different dye-labeled lipids into budding SVs, we did
      not observe an enrichment of lipids with affinity for liquid ordered membrane
      domains. But most importantly, we found no evidence for a static segregation of
      SVs into recycling and resting pools. A small but significant fraction of SVs
      that is reluctant to release during a first round of evoked activity can be
      exocytosed during a second bout of stimulation, showing fast intermixing of SV
      pools within seconds. Furthermore, we found that SVs recycling spontaneously have
      a higher chance to re-occupy release sites than SVs recycling during high
      frequency evoked activity. In summary, our data provide strong evidence for a
      highly dynamic and use-dependent control of the fractions of releasable or
      resting SVs.

PMID- 29456493
TI  - Administration of Ketamine Causes Autophagy and Apoptosis in the Rat Fetal
      Hippocampus and in PC12 Cells.
AB  - Drug abuse during pregnancy is a serious problem. Like alcohol, anticonvulsants,
      sedatives, and anesthetics, such as ketamine, can pass through the placental
      barrier and affect the growing fetus. However, the mechanism by which ketamine
      causes damage to fetal rats is not well understood. Therefore, in this study, we
      anesthetized pregnant rats with ketamine and evaluated the Total Antioxidant
      Capacity (T-AOC), Reactive Oxygen Species (ROS), and Malondialdehyde (MDA).
      Moreover, we determined changes in the levels of Cleaved-Caspase-3 (C-Caspase-3),
      Beclin-1, B-cell lymphoma-2 (Bcl-2), Bcl-2 Associated X Protein (Bax), Autophagy
      related gene 4 (Atg4), Atg5, p62 (SQSTM1), and marker of autophagy Light Chain 3
      (LC3). In addition, we cultured PC12 cells in vitro to determine the relationship
      between ROS, autophagy, and apoptosis following ketamine treatment. The results
      showed that ketamine induced changes in autophagy- and apoptosis-related
      proteins, reduced T-AOC, and generated excessive levels of ROS and MDA. In vitro
      experiments showed similar results, indicating that apoptosis levels can be
      inhibited by 3-MA. We also found that autophagy and apoptosis can be inhibited by
      N-acetyl-L-cysteine (Nac). Thus, anesthesia with ketamine in pregnant rats may
      increase the rate of autophagy and apoptosis in the fetal hippocampus and the
      mechanism may be through inhibition of antioxidant activity and ROS accumulation.

PMID- 29456494
TI  - The Influence of Feedback on Task-Switching Performance: A Drift Diffusion
      Modeling Account.
AB  - Task-switching is an important cognitive skill that facilitates our ability to
      choose appropriate behavior in a varied and changing environment. Task-switching
      training studies have sought to improve this ability by practicing switching
      between multiple tasks. However, an efficacious training paradigm has been
      difficult to develop in part due to findings that small differences in task
      parameters influence switching behavior in a non-trivial manner. Here, for the
      first time we employ the Drift Diffusion Model (DDM) to understand the influence
      of feedback on task-switching and investigate how drift diffusion parameters
      change over the course of task switch training. We trained 316 participants on a
      simple task where they alternated sorting stimuli by color or by shape. Feedback
      differed in six different ways between subjects groups, ranging from No Feedback
      (NFB) to a variety of manipulations addressing trial-wise vs. Block Feedback
      (BFB), rewards vs. punishments, payment bonuses and different payouts depending
      upon the trial type (switch/non-switch). While overall performance was found to
      be affected by feedback, no effect of feedback was found on task-switching
      learning. Drift Diffusion Modeling revealed that the reductions in reaction time
      (RT) switch cost over the course of training were driven by a continually
      decreasing decision boundary. Furthermore, feedback effects on RT switch cost
      were also driven by differences in decision boundary, but not in drift rate.
      These results reveal that participants systematically modified their task
      switching performance without yielding an overall gain in performance.

PMID- 29456495
TI  - Structural Variation of Chondroitin Sulfate Chains Contributes to the Molecular
      Heterogeneity of Perineuronal Nets.
AB  - Aggrecan, a chondroitin sulfate (CS) proteoglycan, forms lattice-like
      extracellular matrix structures called perineuronal nets (PNNs). Neocortical PNNs
      primarily ensheath parvalbumin-expressing inhibitory neurons (parvalbumin, PV
      cells) late in brain development. Emerging evidence indicates that PNNs promote
      the maturation of PV cells by enhancing the incorporation of homeobox protein
      Otx2 and regulating experience-dependent neural plasticity. Wisteria floribunda
      agglutinin (WFA), an N-acetylgalactosamine-specific plant lectin, binds to the CS
      chains of aggrecan and has been widely used to visualize PNNs. Although PNNs show
      substantial molecular heterogeneity, the importance of this heterogeneity in
      neural plasticity remains unknown. Here, in addition to WFA lectin, we used the
      two monoclonal antibodies Cat315 and Cat316, both of which recognize the glycan
      structures of aggrecan, to investigate the molecular heterogeneity of PNNs. WFA
      detected the highest number of PNNs in all cortical layers, whereas Cat315 and
      Cat316 labeled only a subset of PNNs. WFA+, Cat315+, and Cat316+ PNNs showed
      different laminar distributions in the adult visual cortex. WFA, Cat315 and
      Cat316 detected distinct, but partially overlapping, populations of PNNs. Based
      on the reactivities of these probes, we categorized PNNs into four groups. We
      found that two subpopulation of PNNs, one with higher and one with lower WFA
      staining are differentially labeled by Cat316 and Cat315, respectively. CS chains
      recognized by Cat316 were diminished in mice deficient in an enzyme involved in
      the initiation of CS-biosynthesis. Furthermore, WFA+ and Cat316+ aggrecan were
      spatially segregated and formed microdomains in a single PNN. Otx2 co-localized
      with Cat316+ but not with WFA+ aggrecan in PNNs. Our results suggest that the
      heterogeneity of PNNs around PV cells may affect the functional maturation of
      these cells.

PMID- 29456496
TI  - How Do Acquired Political Identities Influence Our Neural Processing toward
      Others within the Context of a Trust Game?
AB  - Trust is essential for mutually beneficial human interactions in economic
      exchange and politics and people's social identities notably have dramatic
      effects on trust behaviors toward others. Previous literature concerning social
      identities generally suggests that people tend to show in-group favoritism toward
      members who share the same identity. However, how our brains process signals of
      identity while facing uncertain situations in interpersonal interactions remains
      largely unclear. To address this issue, we performed an fMRI experiment with 54
      healthy adults who belonged to two identity groups of opposing political
      orientations. The identity information of participants was extracted from a large
      scale social survey on the 2012 Taiwan presidential election. Accordingly,
      participants were categorized as either the Kuomintang (KMT) or the Democratic
      Progressive Party (DPP) supporters. During the experiment, participants played
      trust games with computer agents with labels of the same or the opposing
      political identity. Interestingly, our results suggest that the behaviors of the
      two groups cannot be equally attributed to in-group favoritism. Behaviorally,
      only the DPP supporter group showed a significant trust preference toward in
      group members, which did not hold for the KMT supporter group. Consistently,
      neurophysiological findings further revealed that only the DPP supporter group
      showed neuronal responses to both unexpected negative feedback from in-group
      members in anterior insula, temporoparietal junction, and dorsal lateral
      prefrontal cortex, as well as to unexpected rewards from out-group members in
      caudate. These findings therefore suggest that acquired identities play a more
      complex role in modulating people's social expectation in interpersonal trust
      behaviors under identity-relevant contexts.

PMID- 29456497
TI  - Multiple Looks of Auditory Empty Durations Both Improve and Impair Temporal
      Sensitivity.
AB  - Discrimination of two neighboring empty durations that are marked by three
      successive sounds is improved when the presentation of the first (standard, S)
      duration is repeated before that of the second (comparison, C), as SSSSC. This
      improvement in sensitivity, called the multiple-look effect, has been explained
      by a statistical model regarding variability. This model assumes that the
      perceived duration of the standard is averaged across observations (within a
      trial within an individual). The increasing of the number of observations thus
      reduces the standard error of the mean perceived duration. Alternatively, the
      multiple-look effect is attributed to the listener's prediction based on regular
      rhythm. Listeners perceive regular rhythm during the repetition of the standard,
      predict the timing of subsequent sounds, and detect a sound that is displaced
      from the predicted timing. These models were tested in the present experiment in
      which the main factor was a temporal separation between the standard and the
      comparison; i.e., these durations were adjacent to each other as SSSSC or
      separated by a temporal blank as SSSS_C. The results differed between stimulus
      structures. First, the multiple-look effect was replicated in the SSSSC condition
      (yielding a higher performance than SC), but disappeared in SSSS_C (having no
      difference with S_C). Second, no multiple-look effect occurred in CSSSS (no
      difference with CS), and moreover, an impairment effect was observed in C_SSSS (a
      lower performance than C_S). Finally, discrimination was improved in SSSS_CCCC
      compared with SSSSCCCC, the effect being kept even when sounds were aligned at
      irregular intervals. These findings are not consistent with those expected from
      the statistical model because the temporal separation should have produced no
      effects if the number of standards had been a sole parameter determining the
      multiple-look effect. The prediction-based model can explain the first finding;
      inserting a blank between the standard and the comparison violates the listener's
      prediction based on regular rhythm, thus reducing the multiple-look effect.
      However, it did not expect the other findings and required revisions. Notably,
      the second finding indicates that the formation of regular rhythm can impair
      temporal discrimination. In other words, an inversed multiple-look effect occurs.

PMID- 29456498
TI  - Using SPM 12's Second-Level Bayesian Inference Procedure for fMRI Analysis:
      Practical Guidelines for End Users.
AB  - Recent debates about the conventional traditional threshold used in the fields of
      neuroscience and psychology, namely P < 0.05, have spurred researchers to
      consider alternative ways to analyze fMRI data. A group of methodologists and
      statisticians have considered Bayesian inference as a candidate methodology.
      However, few previous studies have attempted to provide end users of fMRI
      analysis tools, such as SPM 12, with practical guidelines about how to conduct
      Bayesian inference. In the present study, we aim to demonstrate how to utilize
      Bayesian inference, Bayesian second-level inference in particular, implemented in
      SPM 12 by analyzing fMRI data available to public via NeuroVault. In addition, to
      help end users understand how Bayesian inference actually works in SPM 12, we
      examine outcomes from Bayesian second-level inference implemented in SPM 12 by
      comparing them with those from classical second-level inference. Finally, we
      provide practical guidelines about how to set the parameters for Bayesian
      inference and how to interpret the results, such as Bayes factors, from the
      inference. We also discuss the practical and philosophical benefits of Bayesian
      inference and directions for future research.

PMID- 29456499
TI  - Can We Achieve Intuitive Prosthetic Elbow Control Based on Healthy Upper Limb
      Motor Strategies?
AB  - Most transhumeral amputees report that their prosthetic device lacks
      functionality, citing the control strategy as a major limitation. Indeed, they
      are required to control several degrees of freedom with muscle groups primarily
      used for elbow actuation. As a result, most of them choose to have a one-degree
      of-freedom myoelectric hand for grasping objects, a myoelectric wrist for
      pronation/supination, and a body-powered elbow. Unlike healthy upper limb
      movements, the prosthetic elbow joint angle, adjusted prior to the motion, is not
      involved in the overall upper limb movements, causing the rest of the body to
      compensate for the lack of mobility of the prosthesis. A promising solution to
      improve upper limb prosthesis control exploits the residual limb mobility: like
      in healthy movements, shoulder and prosthetic elbow motions are coupled using
      inter-joint coordination models. The present study aims to test this approach. A
      transhumeral amputated individual used a prosthesis with a residual limb motion
      driven elbow to point at targets. The prosthetic elbow motion was derived from
      IMU-based shoulder measurements and a generic model of inter-joint coordinations
      built from healthy individuals data. For comparison, the participant also
      performed the task while the prosthetic elbow was implemented with his own
      myoelectric control strategy. The results show that although the transhumeral
      amputated participant achieved the pointing task with a better precision when the
      elbow was myoelectrically-controlled, he had to develop large compensatory trunk
      movements. Automatic elbow control reduced trunk displacements, and enabled a
      more natural body behavior with synchronous shoulder and elbow motions. However,
      due to socket impairments, the residual limb amplitudes were not as large as
      those of healthy shoulder movements. Therefore, this work also investigates if a
      control strategy whereby prosthetic joints are automatized according to healthy
      individuals' coordination models can lead to an intuitive and natural prosthetic
      control.

PMID- 29456501
TI  - Recommendations for the Design of Serious Games in Neurodegenerative Diseases.
AB  - The use of Serious Games (SG) in the health domain is expanding. In the field of
      Neurodegenerative Diseases (ND) such as Alzheimer's Disease, SG are currently
      employed to provide alternative solutions for patients' treatment, stimulation,
      and rehabilitation. The design of SG for people with ND implies collaborations
      between professionals in ND and professionals in SG design. As the field is quite
      young, professionals specialized in both ND and SG are still rare, and
      recommendations for the design of SG for people with ND are still missing. This
      perspective paper aims to provide recommendations in terms of ergonomic choices
      for the design of SG aiming at stimulating people with ND, starting from the
      existing SG already tested in this population: "MINWii", "Kitchen and Cooking",
      and "X-Torp". We propose to rely on nine ergonomic criteria: eight ergonomic
      criteria inspired by works in the domain of office automation: Compatibility,
      Guidance, Workload, Adaptability, Consistency, Significance of codes, Explicit
      control and Error management; and one ergonomic criterion related to videogame:
      the game rules. Perspectives derived from this proposal are also discussed.

PMID- 29456500
TI  - Auditory Memory Decay as Reflected by a New Mismatch Negativity Score Is
      Associated with Episodic Memory in Older Adults at Risk of Dementia.
AB  - The auditory mismatch negativity (MMN) is an event-related potential (ERP)
      peaking about 100-250 ms after the onset of a deviant tone in a sequence of
      identical (standard) tones. Depending on the interstimulus interval (ISI) between
      standard and deviant tones, the MMN is suitable to investigate the pre-attentive
      auditory discrimination ability (short ISIs, <= 2 s) as well as the pre-attentive
      auditory memory trace (long ISIs, >2 s). However, current results regarding the
      MMN as an index for mild cognitive impairment (MCI) and dementia are mixed,
      especially after short ISIs: while the majority of studies report positive
      associations between the MMN and cognition, others fail to find such
      relationships. To elucidate these so far inconsistent results, we investigated
      the validity of the MMN as an index for cognitive impairment exploring the
      associations between different MMN indices and cognitive performance, more
      specifically with episodic memory performance which is among the most affected
      cognitive domains in the course of Alzheimer's dementia (AD), at baseline and at
      a 5-year-follow-up. We assessed the amplitude of the MMN for short ISI (stimulus
      onset asynchrony, SOA = 0.05 s) and for long ISI (3 s) in a neuropsychologically
      well-characterized cohort of older adults at risk of dementia (subjective memory
      impairment, amnestic and non-amnestic MCI; n = 57). Furthermore, we created a
      novel difference score (DeltaMMN), defined as the difference between MMNs to
      short and to long ISI, as a measure to assess the decay of the auditory memory
      trace, higher values indicating less decay. DeltaMMN and MMN amplitude after long
      ISI, but not the MMN amplitude after short ISI, was associated with episodic
      memory at baseline (beta = 0.38, p = 0.003; beta = -0.27, p = 0.047,
      respectively). DeltaMMN, but not the MMN for long ISIs, was positively associated
      with episodic memory performance at the 5-year-follow-up (beta = 0.57, p =
      0.013). The results suggest that the MMN after long ISI might be suitable as an
      indicator for the decline in episodic memory and indicate DeltaMMN as a potential
      biomarker for memory impairment in older adults at risk of dementia.

PMID- 29456502
TI  - Efficacy of Cognitive Training in Older Adults with and without Subjective
      Cognitive Decline Is Associated with Inhibition Efficiency and Working Memory
      Span, Not with Cognitive Reserve.
AB  - The present study explores the role of cognitive reserve, executive functions,
      and working memory (WM) span, as factors that might explain training outcomes in
      cognitive status. Eighty-one older adults voluntarily participated in the study,
      classified either as older adults with subjective cognitive decline or
      cognitively intact. Each participant underwent a neuropsychological assessment
      that was conducted both at baseline (entailing cognitive reserve, executive
      functions, WM span and depressive symptomatology measures, as well as the Mini
      Mental State Exam regarding initial cognitive status), and then 6 months later,
      once each participant had completed the training program (Mini-Mental State Exam
      at the endpoint). With respect to cognitive status the training program was most
      beneficial for subjective cognitive decline participants with low efficiency in
      inhibition at baseline (explaining a 33% of Mini-Mental State Exam total
      variance), whereas for cognitively intact participants training gains were
      observed for those who presented lower WM span.

PMID- 29456503
TI  - SMO Inhibition Modulates Cellular Plasticity and Invasiveness in Colorectal
      Cancer.
AB  - HIGHLIGHTS Preliminary results of this work were presented at the 2016 Academic
      Surgical Congress, Jacksonville (FL), February 2-4 2016 (Original title:
      Selective Smo-Inhibition Interferes With Cellular Energetic Metabolism In
      Colorectal Cancer)This study was funded by "Sapienza-University of Rome" (Funds
      for young researchers) and "AIRC" (Italian Association for Cancer
      Research)Hedgehog inhibitor was kindly provided by Genentech, Inc.(r). Colon
      Cancer (CC) is the fourth most frequently diagnosed tumor and the second leading
      cause of death in the USA. Abnormalities of Hedgehog pathway have been
      demonstrated in several types of human cancers, however the role of Hedgehog (Hh)
      in CC remain controversial. In this study, we analyzed the association between
      increased mRNA expression of GLI1 and GLI2, two Hh target genes, and CC survival
      and recurrence by gene expression microarray from a cohort of 382 CC patients. We
      found that patients with increased expression of GLI1 showed a statistically
      significant reduction in survival. In order to demonstrate a causal role of Hh
      pathway activation in the pathogenesis of CC, we treated HCT 116, SW480 and SW620
      CC cells lines with GDC-0449, a pharmacological inhibitor of Smoothened (SMO).
      Treatment with GDC-0449 markedly reduced expression of Hh target genes GLI1,
      PTCH1, HIP1, MUC5AC, thus indicating that this pathway is constitutively active
      in CC cell lines. Moreover, GDC-0449 partially reduced cell proliferation, which
      was associated with upregulation of p21 and downregulation of CycD1. Finally,
      treatment with the same drug reduced migration and three-dimensional invasion,
      which were associated with downregulation of Snail1, the EMT master gene, and
      with induction of the epithelial markers Cytokeratin-18 and E-cadherin. These
      results were confirmed by SMO genetic silencing. Notably, treatment with 5E1, a
      Sonic Hedgehog-specific mAb, markedly reduced the expression of Hedgehog target
      genes, as well as inhibited cell proliferation and mediated reversion toward an
      epithelial phenotype. This suggests the existence of a Hedgehog autocrine
      signaling loop affecting cell plasticity and fostering cell proliferation and
      migration/invasion in CC cell lines. These discoveries encourage future
      investigations to better characterize the role of Hedgehog in cellular plasticity
      and invasion during the different steps of CC pathogenesis.

PMID- 29456504
TI  - A Review on Central Nervous System Effects of Gastrodin.
AB  - Rhizoma Gastrodiae (also known as Tian ma), the dried rhizome of Gastrodia elata
      Blume, is a famous Chinese herb that has been traditionally used for the
      treatment of headache, dizziness, spasm, epilepsy, stoke, amnesia and other
      disorders for centuries. Gastrodin, a phenolic glycoside, is the main bioactive
      constituent of Rhizoma Gastrodiae. Since identified in 1978, gastrodin has been
      extensively investigated on its pharmacological properties. In this article, we
      reviewed the central nervous system (CNS) effects of gastrodin in preclinical
      models of CNS disorders including epilepsy, Alzheimer's disease, Parkinson's
      disease, affective disorders, cerebral ischemia/reperfusion, cognitive impairment
      as well as the underlying mechanisms involved and, where possible, clinical data
      that support the pharmacological activities. The sources and pharmacokinetics of
      gastrodin were also reviewed here. As a result, gastrodin possesses a broad range
      of beneficial effects on the above-mentioned CNS diseases, and the mechanisms of
      actions include modulating neurotransmitters, antioxidative, anti-inflammatory,
      suppressing microglial activation, regulating mitochondrial cascades, up
      regulating neurotrophins, etc. However, more detailed clinical trials are still
      in need for positioning it in the treatment of neurological disorders.

PMID- 29456506
TI  - Therapeutic Effects of a Traditional Chinese Medicine Formula Plus Tamoxifen vs.
      Tamoxifen for the Treatment of Mammary Gland Hyperplasia: A Meta-Analysis of
      Randomized Trials.
AB  - As a common disorder that accounts for over 70% of all breast disease cases,
      mammary gland hyperplasia (MGH) causes a severe problem for the quality of
      patients' life, and confers an increased risk of breast carcinoma. However, the
      etiology and pathogenesis of MGH remain unclear, and the safety and efficacy of
      current western drug therapy for MGH still need to be improved. Therefore, a meta
      analysis was conducted by our team to determine whether a TCM formula named Ru-Pi
      Xiao in combination with tamoxifen or Ru-Pi-Xiao treated alone can show more
      prominent therapeutic effects against MGH with fewer adverse reactions than that
      of tamoxifen. Studies published before June 2017 were searched based on
      standardized searching rules in several mainstream medical databases. A total of
      27 articles with 4,368 patients were enrolled in this meta-analysis. The results
      showed that the combination of Ru-Pi-Xiao and tamoxifen could exhibit better
      therapeutic effects against MGH than that of tamoxifen (OR: 3.79; 95% CI: 3.09
      4.65; P < 0.00001) with a lower incidence of adverse reactions (OR: 0.35; 95% CI:
      0.28-0.43; P < 0.00001). The results also suggested that this combination could
      improve the level of progesterone (MD: 2.22; 95% CI: 1.72-2.71; P < 0.00001) and
      decrease the size of breast lump (MD: -0.67; 95% CI: -0.86 to -0.49; P < 0.00001)
      to a greater extent, which might provide a possible explanation for the
      pharmacodynamic mechanism of Ru-Pi-Xiao plus tamoxifen. In conclusion, Ru-Pi-Xiao
      and related preparations could be recommended as auxiliary therapy combined
      tamoxifen for the treatment of MGH.

PMID- 29456505
TI  - Deletion of Trace Amine-Associated Receptor 1 Attenuates Behavioral Responses to
      Caffeine.
AB  - Trace amines (TAs), endogenous amino acid metabolites that are structurally
      similar to the biogenic amines, are endogenous ligands for trace amine-associated
      receptor 1 (TAAR1), a GPCR that modulates dopaminergic, serotonergic, and
      glutamatergic activity. Selective TAAR1 full and partial agonists exhibit similar
      pro-cognitive, antidepressant- and antipsychotic-like properties in rodents and
      non-human primates, suggesting TAAR1 as a novel target for the treatment of
      neurological and psychiatric disorders. We previously reported that TAAR1 partial
      agonists are wake-promoting in rats and mice, and that TAAR1 knockout (KO) and
      overexpressing mice exhibit altered sleep-wake and EEG spectral composition.
      Here, we report that locomotor and EEG spectral responses to the psychostimulants
      modafinil and caffeine are attenuated in TAAR1 KO mice. TAAR1 KO mice and WT
      littermates were instrumented for EEG and EMG recording and implanted with
      telemetry transmitters for monitoring locomotor activity (LMA) and core body
      temperature (Tb). Following recovery, mice were administered modafinil (25, 50,
      100 mg/kg), caffeine (2.5, 10, 20 mg/kg) or vehicle p.o. at ZT6 in balanced
      order. In WT mice, both modafinil and caffeine dose-dependently increased LMA for
      up to 6 h following dosing, whereas only the highest dose of each drug increased
      LMA in KO mice, and did so for less time after dosing. This effect was
      particularly pronounced following caffeine, such that total LMA response was
      significantly attenuated in KO mice compared to WT at all doses of caffeine and
      did not differ from Vehicle treatment. Tb increased comparably in both genotypes
      in a dose-dependent manner. TAAR1 deletion was associated with reduced wake
      consolidation following both drugs, but total time in wakefulness did not differ
      between KO and WT mice. Furthermore, gamma band EEG activity following both
      modafinil and caffeine treatment was attenuated in TAAR1 KO compared to WT mice.
      Our results show that TAAR1 is a critical component of the behavioral and
      cortical arousal associated with two widely used psychostimulants with very
      different mechanisms of action. Together with our previous findings, these data
      suggest that TAAR1 is a previously unrecognized component of an endogenous wake
      modulating system.

PMID- 29456507
TI  - The Effects of Vitamin D Supplementation on Signaling Pathway of Inflammation and
      Oxidative Stress in Diabetic Hemodialysis: A Randomized, Double-Blind, Placebo
      Controlled Trial.
AB  - Objective: This study was carried out to determine the effects of vitamin D
      supplementation on signaling pathway of inflammation and oxidative stress in
      diabetic hemodialysis (HD) patients. Methods: This randomized double-blind
      placebo-controlled clinical trial was conducted among 60 diabetic HD patients.
      Subjects were randomly allocated into two groups to intake either vitamin D
      supplements at a dosage of 50,000 IU (n = 30) or placebo (n = 30) every 2 weeks
      for 12 weeks. Gene expression of inflammatory cytokines and biomarkers of
      oxidative stress were assessed in peripheral blood mononuclear cells (PBMCs) of
      diabetic HD patients with RT-PCR method. Results: Results of RT-PCR indicated
      that after the 12-week intervention, compared to the placebo, vitamin D
      supplementation downregulated gene expression of interleukin (IL)-1beta (P =
      0.02), tumor necrosis factor alpha (TNF-alpha) (P = 0.02) and interferon gamma
      (IFN-gamma) (P = 0.03) in PBMCs of diabetic HD patients. Additionally, vitamin D
      supplementation, compared to the placebo, downregulated gene expression of
      transforming growth factor beta (TGF-beta) (P = 0.04), protein kinase C (PKC) (P
      = 0.001), and mitogen-activated protein kinases 1 (MAPK1) (P = 0.02) in PBMCs of
      diabetic HD patients. Although not significant, vitamin D supplementation let to
      a reduction of nuclear factor kappa B (NF-kB) (p = 0.75) expression in PBMCs
      isolated from diabetic patients compared to the placebo group. There was no
      statistically significant change following supplementation with vitamin D on gene
      expression of interleukin (IL)-4, IL-6, and vascular endothelial growth factor
      (VEGF) in PBMCs of diabetic HD patients. Conclusions: Overall, we found that
      vitamin D supplementation for 12 weeks among diabetic HD patients had beneficial
      effects on few gene expression related to inflammation and oxidative stress.
      Clinical trial registration: IRCT201701035623N101. Registered on January 8, 2017.

PMID- 29456508
TI  - The Molecular Determinants of Small-Molecule Ligand Binding at P2X Receptors.
AB  - P2X receptors are trimeric eukaryotic ATP-gated cation channels. Extracellular
      ATP-their physiological ligand-is released as a neurotransmitter and in
      conditions of cell damage such as inflammation, and substantial evidence
      implicates P2X receptors in diseases including neuropathic pain, cancer, and
      arthritis. In 2009, the first P2X crystal structure, Danio rerio P2X4 in the apo-
      state, was published, and this was followed in 2012 by the ATP-bound structure.
      These structures transformed our understanding of the conformational changes
      induced by ATP binding and the mechanism of ligand specificity, and enabled
      homology modeling of mammalian P2X receptors for ligand docking and rational
      design of receptor modulators. P2X receptors are attractive drug targets, and a
      wide array of potent, subtype-selective modulators (mostly antagonists) have been
      developed. In 2016, crystal structures of human P2X3 in complex with the
      competitive antagonists TNP-ATP and A-317491, and Ailuropoda melanoleuca P2X7 in
      complex with a series of allosteric antagonists were published, giving
      fascinating insights into the mechanism of channel antagonism. In this article we
      not only summarize current understanding of small-molecule modulator binding at
      P2X receptors, but also use this information in combination with previously
      published structure-function data and molecular docking experiments, to
      hypothesize a role for the dorsal fin loop region in differential ATP potency,
      and describe novel, testable binding conformations for both the semi-selective
      synthetic P2X7 agonist 2'-(3')-O-(4-benzoyl)benzoyl ATP (BzATP), and the P2X4
      selective positive allosteric modulator ivermectin. We find that the distal
      benzoyl group of BzATP lies in close proximity to Lys-127, a residue previously
      implicated in BzATP binding to P2X7, potentially explaining the increased potency
      of BzATP at rat P2X7 receptors. We also present molecular docking of ivermectin
      to rat P2X4 receptors, illustrating a plausible binding conformation between the
      first and second transmembrane domains which not only tallies with previous
      mutagenesis studies, but would also likely have the effect of stabilizing the
      open channel structure, consistent with the mode of action of this positive
      allosteric modulator. From our docking simulations and analysis of sequence
      homology we propose a series of mutations likely to confer ivermectin sensitivity
      to human P2X1.

PMID- 29456509
TI  - Curcumin Inhibits Growth of Human NCI-H292 Lung Squamous Cell Carcinoma Cells by
      Increasing FOXA2 Expression.
AB  - Lung squamous cell carcinoma (LSCC) is a common histological lung cancer subtype,
      but unlike lung adenocarcinoma, limited therapeutic options are available for
      treatment. Curcumin, a natural compound, may have anticancer effects in various
      cancer cells, but how it may be used to treat LSCC has not been well studied.
      Here, we applied curcumin to a human NCI-H292 LSCC cell line to test anticancer
      effects and explored underlying potential mechanisms of action. Curcumin
      treatment inhibited NCI-H292 cell growth and increased FOXA2 expression in a time
      dependent manner. FOXA2 expression was decreased in LSCC tissues compared with
      adjacent normal tissues and knockdown of FOXA2 increased NCI-H292 cells
      proliferation. Inhibition of cell proliferation by curcumin was attenuated by
      FOXA2 knockdown. Moreover inhibition of STAT3 pathways by curcumin increased
      FOXA2 expression in NCI-H292 cells whereas a STAT3 activator (IL-6) significantly
      inhibited curcumin-induced FOXA2 expression. Also, SOCS1 and SOCS3, negative
      regulators of STAT3 activity, were upregulated by curcumin treatment. Thus,
      curcumin inhibited human NCI-H292 cells growth by increasing FOXA2 expression via
      regulation of STAT3 signaling pathways.

PMID- 29456510
TI  - Sodium Tanshinone II-A Sulfonate (DS-201) Induces Vasorelaxation of Rat
      Mesenteric Arteries via Inhibition of L-Type Ca2+ Channel.
AB  - Background: We previously have proved that sodium tanshinone II-A sulfonate (DS
      201), a derivative of traditional Chinese medicinal herb Danshen (Salvia
      miltiorrhiza), is an opener and vasodilator of BKCa channel in the vascular
      smooth muscle cells (VSMCs). Vascular tension is closely associated with Ca2+
      dynamics and activation of BKCa channel may not be the sole mechanism for the
      relaxation of the vascular tension by DS-201. Therefore, we hypothesized that the
      vasorelaxing effect of DS-20 may be also related to Ca2+ channel and cytoplasmic
      Ca2+ level in the VSMCs. Methods: Arterial tension was measured by Danish Myo
      Technology (DMT) myograph system in the mesentery vessels of rats, intracellular
      Ca2+ level by fluorescence imaging system in the VSMCs of rats, and L-type Ca2+
      current by patch clamp technique in Ca2+ channels transfected human embryonic
      kidney 293 (HEK-293) cells. Results: DS-201 relaxed the endothelium-denuded
      artery rings pre-constricted with PE or high K+ and the vasorelaxation was
      reversible. Blockade of K+ channel did not totally block the effect of DS-201 on
      vasorelaxation. DS-201 suppressed [Ca2+]i transient induced by high K+ in a
      concentration-dependent manner in the VSMCs, including the amplitude of Ca2+
      transient, the time for Ca2+ transient reaching to the [Ca2+]i peak and the time
      to remove Ca2+ from the cytoplasm. DS-201 inhibited L-type Ca2+ channel with an
      EC50 of 59.5 MUM and at about 40% efficacy of inhibition. However, DS-201did not
      significantly affect the kinetics of Ca2+ channel. The effect of DS-201 on L-type
      Ca2+ channel was rate-independent. Conclusion: The effect of DS-201 on
      vasorelaxation was not only via activating BKCa channel, but also blocking Ca2+
      channel and inhibiting Ca2+ influx in the VSMCs of rats. The results favor the
      use of DS-201 and Danshen in the treatment of cardiovascular diseases clinically.

PMID- 29456511
TI  - P2Y12 Receptors in Tumorigenesis and Metastasis.
AB  - Platelets, beyond their role in hemostasis and thrombosis, may sustain
      tumorigenesis and metastasis. These effects may occur via direct interaction of
      platelets with cancer and stromal cells and by the release of several platelet
      products. Platelets and tumor cells release several bioactive molecules among
      which a great amount of adenosine triphosphate (ATP) and adenosine diphosphate
      (ADP). ADP is also formed extracellularly from ATP breakdown by the ecto
      nucleoside-triphosphate-diphosphohydrolases. Under ATP and ADP stimulation the
      purinergic P2Y1 receptor (R) initiates platelet activation followed by the ADP
      P2Y12R-mediated amplification. P2Y12R stimulation amplifies also platelet
      response to several platelet agonists and to flow conditions, acting as a key
      positive feed-forward signal in intensifying platelet responses. P2Y12R
      represents a potential target for an anticancer therapy due to its involvement in
      platelet-cancer cell crosstalk. Thus, P2Y12R antagonists, including clopidogrel,
      ticagrelor, and prasugrel, might represent potential anti-cancer agents, in
      addition to their role as effective antithrombotic drugs. However, further
      studies, in experimental animals and patients, are required before the
      recommendation of the use of P2Y12R antagonists in cancer prevention and
      progression can be made.

PMID- 29456512
TI  - Local Injections of Superoxide Dismutase Attenuate the Exercise Pressor Reflex in
      Rats with Femoral Artery Occlusion.
AB  - The exercise pressor reflex is amplified in patients with peripheral artery
      disease (PAD) and in an experimental PAD model of rats induced by femoral artery
      occlusion. Heightened blood pressure worsens the restricted blood flow directed
      to the limbs in this disease. The purpose of this study was to determine the role
      played by muscle oxidative stress in regulating the augmented pressor response to
      static exercise in PAD. We hypothesized that limb ischemia impairs muscle
      superoxide dismutase (SOD) thereby leading to abnormal autonomic responsiveness
      observed in PAD animals, and a chronic compensation of SOD for anti-oxidation
      improves the exaggerated exercise pressor reflex. Our data show that femoral
      occlusion decreased the protein levels of SOD in ischemic muscle as compared with
      control muscle. Downregulation of SOD appeared to a greater degree in the
      oxidative (red) muscle than in the glycolytic (white) muscle under the condition
      of muscle ischemia. In addition, the exercise pressor response was assessed
      during electrically induced static contraction. The data demonstrates that the
      enhancement of the exercise pressor reflex was significantly attenuated after
      tempol (a mimetic of SOD, 30 mg over a period of 72 h) was administered into the
      occluded hindlimb. In the occluded rats, mean arterial pressure (MAP) response
      was 26 +/- 3 mmHg with no tempol and 12 +/- 2 mmHg with tempol application (P <
      0.05 vs. group with no tempol; n = 6 in each group). There were no differences in
      muscle tension development (time-tension index: 12.1 +/- 1.2 kgs with no tempol
      and 13.5 +/- 1.1 kgs with tempol; P > 0.05 between groups). In conclusion, SOD is
      lessened in the ischemic muscles and supplement of SOD improves the amplified
      exercise pressor reflex, which is likely beneficial to the restricted blood flow
      to the limbs in PAD.

PMID- 29456513
TI  - Stochastic Effects in Autoimmune Dynamics.
AB  - Among various possible causes of autoimmune disease, an important role is played
      by infections that can result in a breakdown of immune tolerance, primarily
      through the mechanism of "molecular mimicry". In this paper we propose and
      analyse a stochastic model of immune response to a viral infection and subsequent
      autoimmunity, with account for the populations of T cells with different
      activation thresholds, regulatory T cells, and cytokines. We show analytically
      and numerically how stochasticity can result in sustained oscillations around
      deterministically stable steady states, and we also investigate stochastic
      dynamics in the regime of bi-stability. These results provide a possible
      explanation for experimentally observed variations in the progression of
      autoimmune disease. Computations of the variance of stochastic fluctuations
      provide practically important insights into how the size of these fluctuations
      depends on various biological parameters, and this also gives a headway for
      comparison with experimental data on variation in the observed numbers of T cells
      and organ cells affected by infection.

PMID- 29456515
TI  - Relating (Un)acceptability to Interpretation. Experimental Investigations on
      Negation.
AB  - Although contemporary linguistic studies routinely use unacceptable sentences to
      determine the boundary of what falls outside the scope of grammar, investigations
      far more rarely take into consideration the possible interpretations of such
      sentences, perhaps because these interpretations are commonly prejudged as
      irrelevant or unreliable across speakers. In this paper we provide the results of
      two experiments in which participants had to make parallel acceptability and
      interpretation judgments of sentences presenting various types of negative
      dependencies in Basque and in two varieties of Spanish (Castilian Spanish and
      Basque Country Spanish). Our results show that acceptable sentences are uniformly
      assigned a single negation reading in the two languages. However, while
      unacceptable sentences consistently convey single negation in Basque, they are
      interpreted at chance in both varieties of Spanish. These results confirm that
      judgment data that distinguish between acceptable and unacceptable negative
      utterances can inform us not only about an adult's grammar of his/her particular
      language but also about interesting cross-linguistic differences. We conclude
      that the acceptability and interpretation of (un)grammatical negative sentences
      can serve linguistic theory construction by helping to disentangle basic
      assumptions about the nature of various negative dependencies.

PMID- 29456514
TI  - Right Frontotemporal Cortex Mediates the Relationship between Cognitive Insight
      and Subjective Quality of Life in Patients with Schizophrenia.
AB  - Although prior studies identified a relationship between cognitive insight and
      subjective quality of life (QOL) in patients with schizophrenia, the brain
      regions mediating this relationship remain unknown. Recent studies have shown
      that the ventrolateral prefrontal cortex may be particularly important for
      cognitive insight in individuals with schizophrenia. Here, we examined whether
      frontotemporal function mediates the relationship between cognitive insight and
      QOL in 64 participants, including 32 patients with schizophrenia and 32 healthy
      controls. Cognitive insight was measured using the Beck Cognitive Insight Scale
      (BCIS), while participants' subjective QOL was assessed using the Medical
      Outcomes Study 36-item Short-form Health Survey. Frontotemporal function was
      evaluated during a verbal fluency task using multichannel near-infrared
      spectroscopy. Consistent with previous findings, we found that frontotemporal
      function was impaired in patients with schizophrenia. Interestingly, our data
      also revealed that the right ventrolateral PFC and the right anterior part of the
      temporal cortex significantly mediated the relationship between the self
      reflectiveness (SR) subscale of the BCIS and subjective QOL. These findings
      suggest that cognitive insight, particularly SR, is associated with subjective
      QOL in patients with schizophrenia via right frontotemporal function. The
      findings of this study provide important insight into a QOL model of
      schizophrenia, which may guide the development of cost-effective interventions
      that target frontotemporal function in patients with schizophrenia.

PMID- 29456517
TI  - Editorial: Understanding Selfies.

PMID- 29456516
TI  - The Socio-Communicative Development of Preterm Infants Is Resistant to the
      Negative Effects of Parity on Maternal Responsiveness.
AB  - Humans are born completely dependent on adult care for survival. To get the
      necessary support, newborns rely on socio-communicative abilities which have both
      innate and learned components. Maternal responsiveness (MR), as a critical aspect
      of mother-infant interaction, is a robust predictor of the acquisition of socio
      communicative abilities. However, maternal responsiveness (MR) is influenced by
      parity, since mothers rely on a limited capacity of cognitive control for
      efficient attachment with their offspring. This fact is of particular concern for
      preterms, whose developing brain already faces many challenges due to their
      premature emergence from the womb's controlled environment and may still have to
      compete with siblings for mother's attention. Thus, in the present work, we aimed
      to understand how parity interferes with MR and whether it affects the
      development of socio-communicative abilities of preterm infants. We used the
      Social Interaction Rating Scale (SIRS) and the mother-child observation protocol
      in 18 dyads with gestational age <36 weeks. Dyads were separated into three
      groups: primiparous with twin pregnancy (TPM), primiparous (PM), and multiparous
      (MP). Dyadic behavior was evaluated at 3, 6, 9, and 12 months. Our results show
      that offspring size affects MR, but not the socio-communicative development of
      preterm infants during the first year, suggesting a level of resilience of brain
      systems supporting the attachment to caregivers.

PMID- 29456519
TI  - Why Don't You Go to Bed on Time? A Daily Diary Study on the Relationships between
      Chronotype, Self-Control Resources and the Phenomenon of Bedtime Procrastination.
AB  - Background: This daily diary study investigates the phenomenon of bedtime
      procrastination. Bedtime procrastination is defined as going to bed later than
      intended, without having external reasons for doing so. We highlight the role
      chronotype (interindividual differences in biological preferences for sleep-wake
      times) plays for bedtime procrastination. Moreover, we challenge the view that
      bedtime procrastination is the result of a lack of self-regulatory resources by
      investigating momentary self-regulatory resources as a predictor of day-specific
      bedtime procrastination. Methods: One-hundred and eight employees working in
      various industries completed a general electronic questionnaire (to assess
      chronotype and trait self-control) and two daily electronic questionnaires (to
      assess momentary self-regulatory resources before going to bed and day-specific
      bedtime procrastination) over the course of five work days, resulting in 399
      pairs of matched day-next-day measurements. Results: Results of multilevel
      regression analyses showed that later chronotypes (also referred to as evening
      types or 'owls') tended to report more bedtime procrastination on work days.
      Moreover, for late chronotypes, day-specific bedtime procrastination declined
      over the course of the work week. This pattern is in line with expectations
      derived from chronobiology and could not be explained by trait self-control. In
      addition, on evenings on which employees had less self-regulatory resources
      available before going to bed-compared to evenings on which they had more self
      regulatory resources available before going to bed-employees showed lower bedtime
      procrastination. This finding contradicts the prevailing idea that bedtime
      procrastination is the result of a lack of self-regulatory resources. Conclusion:
      The findings of this study provide important implications for how bedtime
      procrastination should be positioned in the field of procrastination as self
      regulatory failure and for how bedtime procrastination should be dealt with in
      practice.

PMID- 29456518
TI  - Environmental Physiology and Diving Medicine.
AB  - Man's experience and exploration of the underwater environment has been recorded
      from ancient times and today encompasses large sections of the population for
      sport enjoyment, recreational and commercial purpose, as well as military
      strategic goals. Knowledge, respect and maintenance of the underwater world is an
      essential development for our future and the knowledge acquired over the last few
      dozen years will change rapidly in the near future with plans to establish secure
      habitats with specific long-term goals of exploration, maintenance and survival.
      This summary will illustrate briefly the physiological changes induced by
      immersion, swimming, breath-hold diving and exploring while using special
      equipment in the water. Cardiac, circulatory and pulmonary vascular adaptation
      and the pathophysiology of novel syndromes have been demonstrated, which will
      allow selection of individual characteristics in order to succeed in various
      environments. Training and treatment for these new microenvironments will be
      suggested with description of successful pioneers in this field. This is a
      summary of the physiology and the present status of pathology and therapy for the
      field.

PMID- 29456520
TI  - Corrigendum: Yoga Poses Increase Subjective Energy and State Self-Esteem in
      Comparison to 'Power Poses'.
AB  - [This corrects the article on p. 752 in vol. 8, PMID: 28553249.].

PMID- 29456522
TI  - Post-Traumatic Hypopituitarism-Who Should Be Screened, When, and How?
AB  - Traumatic brain injury (TBI) remains a major, global public health concern. Over
      the last 15 years, a significant body of evidence has emerged demonstrating that
      post-traumatic hypopituitarism (PTHP) is a common and clinically significant
      consequence of TBI. Non-specific symptomology and the lack of an agreed approach
      to screening for PTHP has led to significant under-diagnosis of this debilitating
      disease. In this review, we will discuss the frequency and clinical significance
      of acute and chronic PTHP as described in the current literature highlighting the
      evidence base for screening and hormone replacement in these patients. We will
      also offer a pragmatic approach to identifying relevant anterior pituitary
      dysfunction after TBI and a follow-up strategy for those patients. Specific
      controversies and remaining unanswered questions will be addressed.

PMID- 29456521
TI  - Mathematical Modeling of Protein Misfolding Mechanisms in Neurological Diseases:
      A Historical Overview.
AB  - Protein misfolding refers to a process where proteins become structurally
      abnormal and lose their specific 3-dimensional spatial configuration. The
      histopathological presence of misfolded protein (MP) aggregates has been
      associated as the primary evidence of multiple neurological diseases, including
      Prion diseases, Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jacob
      disease. However, the exact mechanisms of MP aggregation and propagation, as well
      as their impact in the long-term patient's clinical condition are still not well
      understood. With this aim, a variety of mathematical models has been proposed for
      a better insight into the kinetic rate laws that govern the microscopic processes
      of protein aggregation. Complementary, another class of large-scale models rely
      on modern molecular imaging techniques for describing the phenomenological
      effects of MP propagation over the whole brain. Unfortunately, those neuroimaging
      based studies do not take full advantage of the tremendous capabilities offered
      by the chemical kinetics modeling approach. Actually, it has been barely
      acknowledged that the vast majority of large-scale models have foundations on
      previous mathematical approaches that describe the chemical kinetics of protein
      replication and propagation. The purpose of the current manuscript is to present
      a historical review about the development of mathematical models for describing
      both microscopic processes that occur during the MP aggregation and large-scale
      events that characterize the progression of neurodegenerative MP-mediated
      diseases.

PMID- 29456524
TI  - Saccharomyces cerevisiae and S. kudriavzevii Synthetic Wine Fermentation
      Performance Dissected by Predictive Modeling.
AB  - Wineries face unprecedented challenges due to new market demands and climate
      change effects on wine quality. New yeast starters including non-conventional
      Saccharomyces species, such as S. kudriavzevii, may contribute to deal with some
      of these challenges. The design of new fermentations using non-conventional
      yeasts requires an improved understanding of the physiology and metabolism of
      these cells. Dynamic modeling brings the potential of exploring the most relevant
      mechanisms and designing optimal processes more systematically. In this work we
      explore mechanisms by means of a model selection, reduction and cross-validation
      pipeline which enables to dissect the most relevant fermentation features for the
      species under consideration, Saccharomyces cerevisiae T73 and Saccharomyces
      kudriavzevii CR85. The pipeline involved the comparison of a collection of models
      which incorporate several alternative mechanisms with emphasis on the inhibitory
      effects due to temperature and ethanol. We focused on defining a minimal model
      with the minimum number of parameters, to maximize the identifiability and the
      quality of cross-validation. The selected model was then used to highlight
      differences in behavior between species. The analysis of model parameters would
      indicate that the specific growth rate and the transport of hexoses at initial
      times are higher for S. cervisiae T73 while S. kudriavzevii CR85 diverts more
      flux for glycerol production and cellular maintenance. As a result, the
      fermentations with S. kudriavzevii CR85 are typically slower; produce less
      ethanol but higher glycerol. Finally, we also explored optimal initial
      inoculation and process temperature to find the best compromise between final
      product characteristics and fermentation duration. Results reveal that the
      production of glycerol is distinctive in S. kudriavzevii CR85, it was not
      possible to achieve the same production of glycerol with S. cervisiae T73 in any
      of the conditions tested. This result brings the idea that the optimal design of
      mixed cultures may have an enormous potential for the improvement of final wine
      quality.

PMID- 29456525
TI  - Kinetics and Novel Degradation Pathway of Permethrin in Acinetobacter baumannii
      ZH-14.
AB  - Persistent use of permethrin has resulted in its ubiquitous presence as a
      contaminant in surface streams and soils, yet little is known about the kinetics
      and metabolic behaviors of this pesticide. In this study, a novel bacterial
      strain Acinetobacter baumannii ZH-14 utilizing permethrin via partial hydrolysis
      pathways was isolated from sewage sludge. Response surface methodology based on
      Box-Behnken design of cultural conditions was used for optimization resulting in
      100% degradation of permethrin (50 mg.L-1) within 72 h. Strain ZH-14 degraded
      permethrin up to a concentration of 800 mg.L-1. Biodegradation kinetics analysis
      indicated that permethrin degradation by this strain was concentration dependent,
      with a maximum specific degradation rate, half-saturation constant, and
      inhibition constant of 0.0454 h-1, 4.7912 mg.L-1, and 367.2165 mg.L-1,
      respectively. High-performance liquid chromatography and gas chromatography-mass
      spectrometry identified 3-phenoxybenzenemethanol and 3-phenoxybenzaldehyde as the
      major intermediate metabolites of the permethrin degradation pathway.
      Bioaugmentation of permethrin-contaminated soils with strain ZH-14 significantly
      enhanced degradation, and over 85% of permethrin was degraded within 9 days with
      the degradation process following the first-order kinetic model. In addition to
      degradation of permethrin, strain ZH-14 was capable of degrading a large range of
      synthetic pyrethroids such as deltamethrin, bifenthrin, fenpropathrin,
      cyhalothrin, and beta-cypermethrin which are also widely used pesticides with
      environmental contamination problems, suggesting the promising potentials of A.
      baumannii ZH-14 in bioremediation of pyrethroid-contaminated terrestrial and
      aquatic environments.

PMID- 29456523
TI  - G Protein-Coupled Receptors As Regulators of Localized Translation: The Forgotten
      Pathway?
AB  - G protein-coupled receptors (GPCRs) exert their physiological function by
      transducing a complex signaling network that coordinates gene expression and
      dictates the phenotype of highly differentiated cells. Much is known about the
      gene networks they transcriptionally regulate upon ligand exposure in a process
      that takes hours before a new protein is synthesized. However, far less is known
      about GPCR impact on the translational machinery and subsequent mRNA translation,
      although this gene regulation level alters the cell phenotype in a strikingly
      different timescale. In fact, mRNA translation is an early response kinetically
      connected to signaling events, hence it leads to the synthesis of a new protein
      within minutes following receptor activation. By these means, mRNA translation is
      responsive to subtle variations of the extracellular environment. In addition,
      when restricted to cell subcellular compartments, local mRNA translation
      contributes to cell micro-specialization, as observed in synaptic plasticity or
      in cell migration. The mechanisms that control where in the cell an mRNA is
      translated are starting to be deciphered. But how an extracellular signal
      triggers such local translation still deserves extensive investigations. With the
      advent of high-throughput data acquisition, it now becomes possible to review the
      current knowledge on the translatome that some GPCRs regulate, and how this
      information can be used to explore GPCR-controlled local translation of mRNAs.

PMID- 29456526
TI  - Ammonia-Oxidizing Archaea and Bacteria Differentially Contribute to Ammonia
      Oxidation in Sediments from Adjacent Waters of Rushan Bay, China.
AB  - Ammonia oxidation plays a significant role in the nitrogen cycle in marine
      sediments. Ammonia-oxidizing archaea (AOA) and bacteria (AOB) are the key
      contributors to ammonia oxidation, and their relative contribution to this
      process is one of the most important issues related to the nitrogen cycle in the
      ocean. In this study, the differential contributions of AOA and AOB to ammonia
      oxidation in surface sediments from adjacent waters of Rushan Bay were studied
      based on the ammonia monooxygenase (amoA) gene. Molecular biology techniques were
      used to analyze ammonia oxidizers' community characteristics, and potential
      nitrification incubation was applied to understand the ammonia oxidizers'
      community activity. The objective was to determine the community structure and
      activity of AOA and AOB in surface sediments from adjacent waters of Rushan Bay
      and to discuss the different contributions of AOA and AOB to ammonia oxidation
      during summer and winter seasons in the studied area. Pyrosequencing analysis
      revealed that the diversity of AOA was higher than that of AOB. The majority of
      AOA and AOB clustered into Nitrosopumilus and Nitrosospira, respectively,
      indicating that the Nitrosopumilus group and Nitrosospira groups may be more
      adaptable in studied sediments. The AOA community was closely correlated to
      temperature, salinity and ammonium concentration, whereas the AOB community
      showed a stronger correlation with temperature, chlorophyll-a content (chla) and
      nitrite concentration. qPCR results showed that both the abundance and the
      transcript abundance of AOA was consistently greater than that of AOB. AOA and
      AOB differentially contributed to ammonia oxidation in different seasons. AOB
      occupied the dominant position in mediating ammonia oxidation during summer,
      while AOA might play a dominant role in ammonia oxidation during winter.

PMID- 29456527
TI  - Light as a Broad-Spectrum Antimicrobial.
AB  - Antimicrobial resistance is a significant and growing concern. To continue to
      treat even simple infections, there is a pressing need for new alternative and
      complementary approaches to antimicrobial therapy. One possible addition to the
      current range of treatments is the use of narrow-wavelength light as an
      antimicrobial, which has been shown to eliminate a range of common pathogens.
      Much progress has already been made with blue light but the potential of other
      regions of the electromagnetic spectrum is largely unexplored. In order that the
      approach can be fully and most effectively realized, further research is also
      required into the effects of energy dose, the harmful and beneficial impacts of
      light on eukaryotic tissues, and the role of oxygen in eliciting microbial
      toxicity. These and other topics are discussed within this perspective.

PMID- 29456528
TI  - Mutation in ESBL Plasmid from Escherichia coli O104:H4 Leads Autoagglutination
      and Enhanced Plasmid Dissemination.
AB  - Conjugative plasmids are one of the main driving force of wide-spreading of
      multidrug resistance (MDR) bacteria. They are self-transmittable via conjugation
      as carrying the required set of genes and cis-acting DNA locus for direct cell-to
      cell transfer. IncI incompatibility plasmids are nowadays often associated with
      extended-spectrum beta-lactamases producing Enterobacteria in clinic and
      environment. pESBL-EA11 was isolated from Escherichia coli O104:H4 outbreak
      strain in Germany in 2011. During the previous study identifying transfer genes
      of pESBL-EA11, it was shown that transposon insertion at certain DNA region of
      the plasmid, referred to as Hft, resulted in great enhancement of transfer
      ability. This suggested that genetic modifications can enhance dissemination of
      MDR plasmids. Such 'superspreader' mutations have attracted little attention so
      far despite their high potential to worsen MDR spreading. Present study aimed to
      gain our understanding on regulatory elements that involved pESBL transfer. While
      previous studies of IncI plasmids indicated that immediate downstream gene of
      Hft, traA, is not essential for conjugative transfer, here we showed that
      overexpression of TraA in host cell elevated transfer rate of pESBL-EA11.
      Transposon insertion or certain nucleotide substitutions in Hft led strong TraA
      overexpression which resulted in activation of essential regulator TraB and
      likely overexpression of conjugative pili. Atmospheric Scanning Electron
      Microscopy observation suggested that IncI pili are distinct from other types of
      conjugative pili (such as long filamentous F-type pili) and rather expressed
      throughout the cell surface. High transfer efficiency in the mutant pESBL-EA11
      was involved with hyperpiliation which facilitates cell-to-cell adhesion,
      including autoagglutination. The capability of plasmids to evolve to highly
      transmissible mutant is alarming, particularly it might also have adverse effect
      on host pathogenicity.

PMID- 29456529
TI  - Challenges and Opportunities for Biomarkers of Clinical Response to AHSCT in
      Autoimmunity.
AB  - Autoimmunity represents a broad category of diseases that involve a variety of
      organ targets and distinct autoantigens. For patients with autoimmune diseases
      who fail to respond to approved disease-modifying treatments, autologous
      hematopoietic stem cell transplantation (AHSCT) after high-dose immunosuppressive
      therapy provides an alternative strategy. Although more than 100 studies have
      been published on AHSCT efficacy in autoimmunity, the mechanisms that confer long
      term disease remission as opposed to continued deterioration or disease
      reactivation remain to be determined. In a phase II clinical trial, high-dose
      immunosuppressive therapy combined with autologous CD34+ hematopoietic stem cell
      transplant in treatment-resistant, relapsing-remitting multiple sclerosis (RRMS)
      resulted in 69.2% of participants achieving long-term remission through 60 months
      follow-up. Flow cytometry data from the 24 transplanted participants in the high
      dose immunosuppression and autologous stem cell transplantation for poor
      prognosis multiple sclerosis (HALT-MS) trial are presented to illustrate immune
      reconstitution out to 36 months in patients with aggressive RRMS treated with
      AHSCT and to highlight experimental challenges inherent in identifying biomarkers
      for relapse and long-term remission through 60 months follow-up. AHSCT induced
      changes in numbers of CD4 T cells and in the composition of CD4 and CD8 T cells
      that persisted through 36 months in participants who maintained disease remission
      through 60 months. However, changes in T cell phenotypes studied were unable to
      clearly discriminate durable remission from disease reactivation after AHSCT,
      possibly due to the small sample size, limited phenotypes evaluated in this real
      time assay, and other limitations of the HALT-MS study population. Strategies and
      future opportunities for identifying biomarkers of clinical outcome to AHSCT in
      autoimmunity are also discussed.

PMID- 29456530
TI  - Donor Genotype in the Interleukin-7 Receptor alpha-Chain Predicts Risk of Graft
      versus-Host Disease and Cytomegalovirus Infection after Allogeneic Hematopoietic
      Stem Cell Transplantation.
AB  - The efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) is
      challenged by acute and chronic graft-versus-host disease (aGVHD and cGVHD) and
      viral infections due to long-lasting immunodeficiency. Interleukin-7 (IL-7) is a
      cytokine essential for de novo T cell generation in thymus and peripheral T cell
      homeostasis. In this study, we investigated the impact of the single nucleotide
      polymorphism rs6897932 in the IL-7 receptor alpha-chain (IL-7Ralpha) which has
      previously been associated with several autoimmune diseases. We included 460
      patients undergoing allogeneic HSCT after a myeloablative conditioning. Patients
      had a median age of 26.3 years (0.3-67.0 years), and 372 (80.9%) underwent HSCT
      for malignant diseases. Donors were matched sibling donors (n = 147), matched
      unrelated donors (n = 244) or mismatched unrelated donors (n = 69), and the stem
      cell source were either bone marrow (n = 329) or peripheral blood (n = 131). DNA
      from donors was genotyped for the IL-7Ralpha single nucleotide polymorphism (SNP)
      rs6897932 using an allele-specific primer extension assay (CC: n = 252, CT: n =
      178, TT: n = 30). The donor T allele was associated with a higher risk of grades
      III-IV aGVHD (HR = 2.0, 95% CI = 1.1-3.8, P = 0.034) and with significantly
      increased risk of extensive cGVHD (HR = 2.0, 95% CI = 1.1-3.6, P = 0.025) after
      adjustment for potential risk factors. In addition, the TT genotype was
      associated with a higher risk of cytomegalovirus (CMV) infection post-transplant
      (HR = 2.4, 95% CI = 1.2-4.3, P = 0.0068). Numbers of T cells were significantly
      higher on day +60 in patients receiving a rs6897932 TT graft (CD3+: 109%
      increase, P = 0.0096; CD4+: 64% increase, P = 0.038; CD8+: 133% increase, P =
      0.011). Donor heterozygosity for the T allele was associated with inferior
      overall survival (HR = 1.7, 95% CI = 1.2-2.3, P = 0.0027) and increased treatment
      related mortality (HR = 2.3, 95% CI = 1.3-4.0, P = 0.0047), but was not
      associated with the risk of relapse (P = 0.35). In conclusion, the IL-7Ralpha
      rs6897932 genotype of the donor is predictive of aGVHD and cGVHD, CMV infection,
      and mortality following HSCT. These findings indicate that IL-7Ralpha SNP typing
      of donors may optimize donor selection and facilitate individualization of
      treatment in order to limit treatment-related complications.

PMID- 29456531
TI  - First Occurrence of Plasmablastic Lymphoma in Adenosine Deaminase-Deficient
      Severe Combined Immunodeficiency Disease Patient and Review of the Literature.
AB  - Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID)
      is a primary immune deficiency characterized by mutations in the ADA gene
      resulting in accumulation of toxic compounds affecting multiple districts.
      Hematopoietic stem cell transplantation (HSCT) from a matched donor and
      hematopoietic stem cell gene therapy are the preferred options for definitive
      treatment. Enzyme replacement therapy (ERT) is used to manage the disease in the
      short term, while a decreased efficacy is reported in the medium-long term. To
      date, eight cases of lymphomas have been described in ADA-SCID patients. Here we
      report the first case of plasmablastic lymphoma occurring in a young adult with
      ADA-SCID on long-term ERT, which turned out to be Epstein-Barr virus associated.
      The patient previously received infusions of genetically modified T cells. A
      cumulative analysis of the eight published cases of lymphoma from 1992 to date,
      and the case here described, reveals a high mortality (89%). The most common form
      is diffuse large B-cell lymphoma, which predominantly occurs in extra nodal
      sites. Seven cases occurred in patients on ERT and two after haploidentical HSCT.
      The significant incidence of immunodeficiency-associated lymphoproliferative
      disorders and poor survival of patients developing this complication highlight
      the priority in finding a prompt curative treatment for ADA-SCID.

PMID- 29456532
TI  - A Stretch of Negatively Charged Amino Acids of Linker for Activation of T-Cell
      Adaptor Has a Dual Role in T-Cell Antigen Receptor Intracellular Signaling.
AB  - The adaptor protein linker for activation of T cells (LAT) has an essential role
      transducing activatory intracellular signals coming from the TCR/CD3 complex.
      Previous reports have shown that upon T-cell activation, LAT interacts with the
      tyrosine kinase Lck, leading to the inhibition of its kinase activity. LAT-Lck
      interaction seemed to depend on a stretch of negatively charged amino acids in
      LAT. Here, we have substituted this segment of LAT between amino acids 113 and
      126 with a non-charged segment and expressed the mutant LAT (LAT-NIL) in J.CaM2
      cells in order to analyze TCR signaling. Substitution of this segment in LAT
      prevented the activation-induced interaction with Lck. Moreover, cells expressing
      this mutant form of LAT showed a statistically significant increase of proximal
      intracellular signals such as phosphorylation of LAT in tyrosine residues 171 and
      191, and also enhanced ZAP70 phosphorylation approaching borderline statistical
      significance (p = 0.051). Nevertheless, downstream signals such as Ca2+ influx or
      MAPK pathways were partially inhibited. Overall, our data reveal that LAT-Lck
      interaction constitutes a key element regulating proximal intracellular signals
      coming from the TCR/CD3 complex.

PMID- 29456533
TI  - Non-Hematopoietic MLKL Protects Against Salmonella Mucosal Infection by Enhancing
      Inflammasome Activation.
AB  - The intestinal mucosal barrier is critical for host defense against pathogens
      infection. Here, we demonstrate that the mixed lineage kinase-like protein
      (MLKL), a necroptosis effector, promotes intestinal epithelial barrier function
      by enhancing inflammasome activation. MLKL-/- mice were more susceptible to
      Salmonella infection compared with wild-type counterparts, with higher mortality
      rates, increased body weight loss, exacerbated intestinal inflammation, more
      bacterial colonization, and severe epithelial barrier disruption. MLKL deficiency
      promoted early epithelial colonization of Salmonella prior to developing apparent
      intestinal pathology. Active MLKL was predominantly expressed in crypt epithelial
      cells, and experiments using bone marrow chimeras found that the protective
      effects of MLKL were dependent on its expression in non-hematopoietic cells.
      Intestinal mucosa of MLKL-/- mice had impaired caspase-1 and gasdermin D
      cleavages and decreased interleukin (IL)-18 release. Moreover, administration of
      exogenous recombinant IL-18 rescued the phenotype of increased bacterial
      colonization in MLKL-/- mice. Thus, our results uncover the role of MLKL in
      enhancing inflammasome activation in intestinal epithelial cells to inhibit early
      bacterial colonization.

PMID- 29456534
TI  - Critical Role of TGF-beta and IL-2 Receptor Signaling in Foxp3 Induction by an
      Inhibitor of DNA Methylation.
AB  - Under physiological conditions, CD4+ regulatory T (Treg) cells expressing the
      transcription factor Foxp3 are generated in the thymus [thymus-derived Foxp3+
      Treg (tTregs) cells] and extrathymically at peripheral sites [peripherally
      induced Foxp3+ Treg (pTreg) cell], and both developmental subsets play non
      redundant roles in maintaining self-tolerance throughout life. In addition, a
      variety of experimental in vitro and in vivo modalities can extrathymically
      elicit a Foxp3+ Treg cell phenotype in peripheral CD4+Foxp3- T cells, which has
      attracted much interest as an approach toward cell-based therapy in clinical
      settings of undesired immune responses. A particularly notable example is the in
      vitro induction of Foxp3 expression and Treg cell activity (iTreg cells) in
      initially naive CD4+Foxp3- T cells through T cell receptor (TCR) and IL-2R
      ligation, in the presence of exogenous TGF-beta. Clinical application of Foxp3+
      iTreg cells has been hampered by the fact that TGF-beta-driven Foxp3 induction is
      not sufficient to fully recapitulate the epigenetic and transcriptional signature
      of in vivo induced Foxp3+ tTreg and pTreg cells, which includes the failure to
      imprint iTreg cells with stable Foxp3 expression. This hurdle can be potentially
      overcome by pharmacological interference with DNA methyltransferase activity and
      CpG methylation [e.g., by the cytosine nucleoside analog 5-aza-2'-deoxycytidine
      (5-aza-dC)] to stabilize TGF-beta-induced Foxp3 expression and to promote a
      Foxp3+ iTreg cell phenotype even in the absence of added TGF-beta. However, the
      molecular mechanisms of 5-aza-dC-mediated Foxp3+ iTreg cell generation have
      remained incompletely understood. Here, we show that in the absence of
      exogenously added TGF-beta and IL-2, efficient 5-aza-dC-mediated Foxp3+ iTreg
      cell generation from TCR-stimulated CD4+Foxp3- T cells is critically dependent on
      TGF-betaR and IL-2R signaling and that this process is driven by TGF-beta and IL
      2, which could either be FCS derived or produced by T cells on TCR stimulation.
      Overall, these findings contribute to our understanding of the molecular
      mechanisms underlying the process of Foxp3 induction and may provide a rational
      basis for generating phenotypically and functionally stable iTreg cells.

PMID- 29456535
TI  - Liver X Receptor Agonist Therapy Prevents Diffuse Alveolar Hemorrhage in Murine
      Lupus by Repolarizing Macrophages.
AB  - : The generation of CD138+ phagocytic macrophages with an alternative (M2)
      phenotype that clear apoptotic cells from tissues is defective in lupus. Liver X
      receptor-alpha (LXRalpha) is an oxysterol-regulated transcription factor that
      promotes reverse cholesterol transport and alternative (M2) macrophage
      activation. Conversely, hypoxia-inducible factor 1-alpha (HIF1alpha) promotes
      classical (M1) macrophage activation. The objective of this study was to see if
      lupus can be treated by enhancing the generation of M2-like macrophages using LXR
      agonists. Peritoneal macrophages from pristane-treated mice had an M1 phenotype,
      high HIFalpha-regulated phosphofructokinase and TNFalpha expression (quantitative
      PCR, flow cytometry), and low expression of the LXRalpha-regulated gene ATP
      binding cassette subfamily A member 1 (Abca1) and Il10 vs. mice treated with
      mineral oil, a control inflammatory oil that does not cause lupus. Glycolytic
      metabolism (extracellular flux assays) and Hif1a expression were higher in
      pristane-treated mice (M1-like) whereas oxidative metabolism and LXRalpha
      expression were higher in mineral oil-treated mice (M2-like). Similarly, lupus
      patients' monocytes exhibited low LXRalpha/ABCA1 and high HIF1alpha vs. CONTROLS:
      The LXR agonist T0901317 inhibited type I interferon and increased ABCA1 in lupus
      patients' monocytes and in murine peritoneal macrophages. In vivo, T0901317
      induced M2-like macrophage polarization and protected mice from diffuse alveolar
      hemorrhage (DAH), an often fatal complication of lupus. We conclude that end
      organ damage (DAH) in murine lupus can be prevented using an LXR agonist to
      correct a macrophage differentiation abnormality characteristic of lupus. LXR
      agonists also decrease inflammatory cytokine production by human lupus monocytes,
      suggesting that these agents may be have a role in the pharmacotherapy of lupus.

PMID- 29456536
TI  - Janus-Faced Myeloid-Derived Suppressor Cell Exosomes for the Good and the Bad in
      Cancer and Autoimmune Disease.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of
      immature myeloid cells originally described to hamper immune responses in chronic
      infections. Meanwhile, they are known to be a major obstacle in cancer
      immunotherapy. On the other hand, MDSC can interfere with allogeneic transplant
      rejection and may dampen autoreactive T cell activity. Whether MDSC-Exosomes
      (Exo) can cope with the dangerous and potentially therapeutic activities of MDSC
      is not yet fully explored. After introducing MDSC and Exo, it will be discussed,
      whether a blockade of MDSC-Exo could foster the efficacy of immunotherapy in
      cancer and mitigate tumor progression supporting activities of MDSC. It also will
      be outlined, whether application of native or tailored MDSC-Exo might prohibit
      autoimmune disease progression. These considerations are based on the steadily
      increasing knowledge on Exo composition, their capacity to distribute throughout
      the organism combined with selectivity of targeting, and the ease to tailor Exo
      and includes open questions that answers will facilitate optimizing protocols for
      a MDSC-Exo blockade in cancer as well as for strengthening their therapeutic
      efficacy in autoimmune disease.

PMID- 29456537
TI  - Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple
      Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird's Eye View.
AB  - The increased use of newer potent immunomodulatory therapies for multiple
      sclerosis (MS), including natalizumab, fingolimod, and dimethyl fumarate, has
      expanded the patient population at risk for developing progressive multifocal
      leukoencephalopathy (PML). These MS therapies shift the profile of lymphocytes
      within the central nervous system (CNS) leading to increased anti-inflammatory
      subsets and decreased immunosurveillance. Similar to MS, PML is a demyelinating
      disease of the CNS, but it is caused by the JC virus. The manifestation of PML
      requires the presence of an active, genetically rearranged form of the JC virus
      within CNS glial cells, coupled with the loss of appropriate JC virus-specific
      immune responses. The reliability of metrics used to predict risk for PML could
      be improved if all three components, i.e., viral genetic strain, localization,
      and host immune function, were taken into account. Advances in our understanding
      of the critical lymphocyte subpopulation changes induced by these MS therapies
      and ability to detect viral mutation and reactivation will facilitate efforts to
      develop these metrics.

PMID- 29456538
TI  - An Uncoupling of Canonical Phenotypic Markers and Functional Potency of Ex Vivo
      Expanded Natural Killer Cells.
AB  - Recent advances in cellular therapies for patients with cancer, including
      checkpoint blockade and ex vivo-expanded, tumor-specific T cells, have
      demonstrated that targeting the immune system is a powerful approach to the
      elimination of tumor cells. Clinical efforts have also demonstrated limitations,
      however, including the potential for tumor cell antigenic drift and neoantigen
      formation, which promote tumor escape and recurrence, as well as rapid onset of T
      cell exhaustion in vivo. These findings suggest that antigen unrestricted cells,
      such as natural killer (NK) cells, may be beneficial for use as an alternative to
      or in combination with T cell based approaches. Although highly effective in
      lysing transformed cells, to date, few clinical trials have demonstrated
      antitumor function or persistence of transferred NK cells. Several recent studies
      describe methods to expand NK cells for adoptive transfer, although the effects
      of ex vivo expansion are not fully understood. We therefore explored the impact
      of a clinically validated 12-day expansion protocol using a K562 cell line
      expressing membrane-bound IL-15 and 4-1BB ligand with high-dose soluble IL-2 on
      the phenotype and functions of NK cells from healthy donors. Following expansions
      using this protocol, we found expression of surface proteins that implicate
      preferential expansion of NK cells that are not fully mature, as is typically
      associated with highly cytotoxic NK cell subsets. Despite increased expression of
      markers associated with functional exhaustion in T cells, we found that ex vivo
      expanded NK cells retained cytokine production capacity and had enhanced tumor
      cell cytotoxicity. The preferential expansion of an NK cell subset that is
      phenotypically immature and functionally pleiotropic suggests that adoptively
      transferred cells may persist better in vivo when compared with previous methods
      using this approach. Ex vivo expansion does not quell killer immunoglobulin-like
      receptor diversity, allowing responsiveness to various factors in vivo that may
      influence activation and inhibition. Collectively, our data suggest that in
      addition to robust NK cell expansion that has been described using this method,
      expanded NK cells may represent an ideal cell therapy that is longer lived,
      highly potent, and responsive to an array of activating and inhibitory signals.

PMID- 29456539
TI  - Generation of Human Immunosuppressive Myeloid Cell Populations in Human
      Interleukin-6 Transgenic NOG Mice.
AB  - The tumor microenvironment contains unique immune cells, termed myeloid-derived
      suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that suppress
      host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although
      these cells are considered a key target of cancer immune therapy, in vivo animal
      models allowing differentiation of human immunosuppressive myeloid cells have yet
      to be established, hampering the development of novel cancer therapies. In this
      study, we established a novel humanized transgenic (Tg) mouse strain, human
      interleukin (hIL)-6-expressing NOG mice (NOG-hIL-6 transgenic mice). After
      transplantation of human hematopoietic stem cells (HSCs), the HSC-transplanted
      NOG-hIL-6 Tg mice (HSC-NOG-hIL-6 Tg mice) showed enhanced human
      monocyte/macrophage differentiation. A significant number of human monocytes were
      negative for HLA-DR expression and resembled immature myeloid cells in the spleen
      and peripheral blood from HSC-NOG-hIL-6 Tg mice, but not from HSC-NOG non-Tg
      mice. Engraftment of HSC4 cells, a human head and neck squamous cell carcinoma
      derived cell line producing various factors including IL-6, IL-1beta, macrophage
      colony-stimulating factor (M-CSF), and vascular endothelial growth factor (VEGF),
      into HSC-NOG-hIL-6 Tg mice induced a significant number of TAM-like cells, but
      few were induced in HSC-NOG non-Tg mice. The tumor-infiltrating macrophages in
      HSC-NOG-hIL-6 Tg mice expressed a high level of CD163, a marker of
      immunoregulatory myeloid cells, and produced immunosuppressive molecules such as
      arginase-1 (Arg-1), IL-10, and VEGF. Such cells from HSC-NOG-hIL-6 Tg mice, but
      not HSC-NOG non-Tg mice, suppressed human T cell proliferation in response to
      antigen stimulation in in vitro cultures. These results suggest that functional
      human TAMs can be developed in NOG-hIL-6 Tg mice. This mouse model will
      contribute to the development of novel cancer immune therapies targeting
      immunoregulatory/immunosuppressive myeloid cells.

PMID- 29456540
TI  - Kallikrein-Kinin System Suppresses Type I Interferon Responses: A Novel Pathway
      of Interferon Regulation.
AB  - The Kallikrein-Kinin System (KKS), comprised of kallikreins (klks), bradykinins
      (BKs) angiotensin-converting enzyme (ACE), and many other molecules, regulates a
      number of physiological processes, including inflammation, coagulation,
      angiogenesis, and control of blood pressure. In this report, we show that KKS
      regulates Type I IFN responses, thought to be important in lupus pathogenesis. We
      used CpG (TLR9 ligand), R848 (TLR7 ligand), or recombinant IFN-alpha to induce
      interferon-stimulated genes (ISGs) and proteins, and observed that this response
      was markedly diminished by BKs, klk1 (tissue kallikrein), or captopril (an ACE
      inhibitor). BKs significantly decreased the ISGs induced by TLRs in vitro and in
      vivo (in normal and lupus-prone mice), and in human PBMCs, especially the
      induction of Irf7 gene (p < 0.05), the master regulator of Type I IFNs. ISGs
      induced by IFN-alpha were also suppressed by the KKS. MHC Class I upregulation, a
      classic response to Type I IFNs, was reduced by BKs in murine dendritic cells
      (DCs). BKs decreased phosphorylation of STAT2 molecules that mediate IFN
      signaling. Among the secreted pro-inflammatory cytokines/chemokines analyzed (IL
      6, IL12p70, and CXCL10), the strongest suppressive effect was on CXCL10, a highly
      Type I IFN-dependent cytokine, upon CpG stimulation, both in normal and lupus
      prone DCs. klks that break down into BKs, also suppressed CpG-induced ISGs in
      murine DCs. Captopril, a drug that inhibits ACE and increases BK, suppressed
      ISGs, both in mouse DCs and human PBMCs. The effects of BK were reversed with
      indomethacin (compound that inhibits production of PGE2), suggesting that BK
      suppression of IFN responses may be mediated via prostaglandins. These results
      highlight a novel regulatory mechanism in which members of the KKS control the
      Type I IFN response and suggest a role for modulators of IFNs in the pathogenesis
      of lupus and interferonopathies.

PMID- 29456542
TI  - Editorial: Advances in Ascochyta Research.

PMID- 29456541
TI  - IFN-tau Mediated Control of Bovine Major Histocompatibility Complex Class I
      Expression and Function via the Regulation of bta-miR-148b/152 in Bovine
      Endometrial Epithelial Cells.
AB  - IFN-tau, a type I interferon produced by the trophoblasts of ruminants, has
      various important immune functions, including effects on the expression of major
      histocompatibility complex (MHC) class I (MHC-I). A previous study has reported
      that IFN-tau promotes the expression of MHC-I molecules on endometrial cells.
      However, the immunological mechanisms by which IFN-tau regulates MHC-I molecules
      remain unknown. Here, we investigated which microRNA (miRNAs) may be involved in
      the regulation of MHC-I molecule expression and function in bovine endometrial
      epithelial cells (bEECs). By using TargetScan 6.2 and http://www.microRNA.org,
      two miRNAs were suggested to target the 3'UTR of the bovine MHC-I heavy chain:
      bta-miR-148b and bta-miR-152. Dual luciferase reporter and miRNA mimic/inhibitor
      assays suggested that bta-miR-148b/152 were negatively correlated with bovine MHC
      I heavy chain genes. The function of the MHC-I heavy chain was then investigated
      using qRT-PCR, ELISA, western blotting, immunofluorescence, and RNA interference
      assays in primary bEECs and an endometrial epithelial cell line (BEND). The
      results demonstrated that bta-miR-148b/152 could promote TLR4-triggered
      inflammatory responses by targeting the bovine MHC-I heavy chain, and the MHC-I
      molecule negatively regulated TLR4-induced inflammatory reactions may through the
      Fps-SHP-2 pathway. Our discovery offers novel insight into negative regulation of
      the TLR4 pathway and elucidates the mechanism by which bovine MHC-I molecules
      control congenital inflammatory reactions.

PMID- 29456543
TI  - No Interactions of Stacked Bt Maize with the Non-target Aphid Rhopalosiphum padi
      and the Spider Mite Tetranychus urticae.
AB  - In the agroecosystem, genetically engineered plants producing insecticidal Cry
      proteins from Bacillus thuringiensis (Bt) interact with non-target herbivores and
      other elements of the food web. Stacked Bt crops expose herbivores to multiple
      Cry proteins simultaneously. In this study, the direct interactions between
      SmartStax(r) Bt maize producing six different Cry proteins and two herbivores
      with different feeding modes were investigated. Feeding on leaves of Bt maize had
      no effects on development time, fecundity, or longevity of the aphid
      Rhopalosiphum padi (Hemiptera: Aphididae), and no effects on the egg hatching
      time, development time, sex ratio, fecundity, and survival of the spider mite
      Tetranychus urticae (Acari: Tetranychidae). The results thus confirm the lack of
      effects on those species reported previously for some of the individual Cry
      proteins. In the Bt maize leaves, herbivore infestation did not result in a
      consistent change of Cry protein concentrations. However, occasional statistical
      differences between infested and non-infested leaves were observed for some Cry
      proteins and experimental repetitions. Overall, the study provides evidence that
      the Cry proteins in stacked Bt maize do not interact with two common non-target
      herbivores.

PMID- 29456545
TI  - The Dangers of Being a Small, Oligotrophic and Light Demanding Freshwater Plant
      across a Spatial and Historical Eutrophication Gradient in Southern Scandinavia.
AB  - European freshwater habitats have experienced a severe loss of plant diversity,
      regionally and locally, over the last century or more. One important and well
      established driver of change is eutrophication, which has increased with rising
      population density and agricultural intensification. However, reduced disturbance
      of lake margins may have played an additional key role. The geographical
      variation in water chemistry, which has set the scene for - and interacted with -
      anthropogenic impact, is much less well understood. We took advantage of some
      recently completed regional plant distribution surveys, relying on hundreds of
      skilled citizen scientists, and analyzed the hydrophyte richness to environment
      relations in five contiguous South-Scandinavian regions. For three of the
      regions, we also assessed changes to the freshwater flora over the latest 50-80
      years. We found a considerable variation in background total phosphorus
      concentrations and alkalinity, both within and between regions. The prevalence of
      functional groups differed between regions in accordance with the environmental
      conditions and the species' tolerance to turbid waters. Similarly, the historical
      changes within regions followed the same trend in correspondence to the altered
      environmental conditions over time. Small submerged species decreased relative to
      tall submerged and floating-leaved species along the regional and historical
      eutrophication gradients. These changes were accompanied by systematically
      greater relative abundance of species of higher phosphorus prevalence. We
      conclude that species traits in close correspondence with anthropogenic impacts
      are the main determinants of local, regional and historical changes of species
      distribution and occupancy, while pure biogeography plays a minor role.
      Conservation measures, such as re-oligotrophication and re-established
      disturbance regimes through grazing and water level fluctuations, may help reduce
      the tall reed vegetation, restore the former richness of the freshwater flora and
      safeguard red-listed species, although extended time delays are anticipated in
      nutrient-rich regions, in which species only survive at minute abundance in
      isolated refugia.

PMID- 29456544
TI  - Inheritance of Mesotrione Resistance in an Amaranthus tuberculatus (var. rudis)
      Population from Nebraska, USA.
AB  - A population of Amaranthus tuberculatus (var. rudis) evolved resistance to 4
      hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor herbicides (mesotrione,
      tembotrione, and topramezone) in Nebraska. The level of resistance was the
      highest to mesotrione, and the mechanism of resistance in this population is
      metabolism-based likely via cytochrome P450 enzymes. The increasing number of
      weeds resistant to herbicides warrants studies on the ecology and evolutionary
      factors contributing for resistance evolution, including inheritance of
      resistance traits. In this study, we investigated the genetic control of
      mesotrione resistance in an A. tuberculatus population from Nebraska, USA.
      Results showed that reciprocal crosses in the F1 families exhibited nuclear
      inheritance, which allows pollen movement carrying herbicide resistance alleles.
      The mode of inheritance varied from incomplete recessive to incomplete dominance
      depending upon the F1 family. Observed segregation patterns for the majority of
      the F2 and back-cross susceptible (BC/S) families did not fit to a single major
      gene model. Therefore, multiple genes are likely to confer metabolism-based
      mesotrione resistance in this A. tuberculatus population from Nebraska. The
      results of this study aid to understand the genetics and inheritance of a non
      target-site based mesotrione resistant A. tuberculatus population from Nebraska,
      USA.

PMID- 29456546
TI  - Genome-Wide Association Studies and Comparison of Models and Cross-Validation
      Strategies for Genomic Prediction of Quality Traits in Advanced Winter Wheat
      Breeding Lines.
AB  - The aim of the this study was to identify SNP markers associated with five
      important wheat quality traits (grain protein content, Zeleny sedimentation, test
      weight, thousand-kernel weight, and falling number), and to investigate the
      predictive abilities of GBLUP and Bayesian Power Lasso models for genomic
      prediction of these traits. In total, 635 winter wheat lines from two breeding
      cycles in the Danish plant breeding company Nordic Seed A/S were phenotyped for
      the quality traits and genotyped for 10,802 SNPs. GWAS were performed using
      single marker regression and Bayesian Power Lasso models. SNPs with large effects
      on Zeleny sedimentation were found on chromosome 1B, 1D, and 5D. However, GWAS
      failed to identify single SNPs with significant effects on the other traits,
      indicating that these traits were controlled by many QTL with small effects. The
      predictive abilities of the models for genomic prediction were studied using
      different cross-validation strategies. Leave-One-Out cross-validations resulted
      in correlations between observed phenotypes corrected for fixed effects and
      genomic estimated breeding values of 0.50 for grain protein content, 0.66 for
      thousand-kernel weight, 0.70 for falling number, 0.71 for test weight, and 0.79
      for Zeleny sedimentation. Alternative cross-validations showed that the genetic
      relationship between lines in training and validation sets had a bigger impact on
      predictive abilities than the number of lines included in the training set. Using
      Bayesian Power Lasso instead of GBLUP models, gave similar or slightly higher
      predictive abilities. Genomic prediction based on all SNPs was more effective
      than prediction based on few associated SNPs.

PMID- 29456547
TI  - Evolutionary Origin, Gradual Accumulation and Functional Divergence of Heat Shock
      Factor Gene Family with Plant Evolution.
AB  - Plants, as sessile organisms, evolved a complex and functionally diverse heat
      shock factor (HSF) gene family to cope with various environmental stresses.
      However, the limited evolution studies of the HSF gene family have hindered our
      understanding of environmental adaptations in plants. In this study, a
      comprehensive evolution analysis on the HSF gene family was performed in 51
      representative plant species. Our results demonstrated that the HSFB group which
      lacks a typical AHA activation domain, was the most ancient, and is under
      stronger purifying selection pressure in the subsequent evolutionary processes.
      While, dramatic gene expansion and functional divergence occurred at evolution
      timescales corresponding to plant land inhabit, which contribute to the emergence
      and diversification of the HSFA and HSFC groups in land plants. During the plant
      evolution, the ancestral functions of HSFs were maintained by strong purifying
      pressure that acted on the DNA binding domain, while the variable oligomerization
      domain and motif organization of HSFs underwent functional divergence and
      generated novel subfamilies. At the same time, variations were further
      accumulated with plant evolution, and this resulted in remarkable functional
      diversification among higher plant lineages, including distinct HSF numbers and
      selection pressures of several HSF subfamilies between monocots and eudicots,
      highlighting the fundamental differences in different plant lineages in response
      to environmental stresses. Taken together, our study provides novel insights into
      the evolutionary origin, pattern and selection pressure of plant HSFs and
      delineates critical clues that aid our understanding of the adaptation processes
      of plants to terrestrial environments.

PMID- 29456548
TI  - GABA Shunt in Durum Wheat.
AB  - Plant responses to salinity are complex, especially when combined with other
      stresses, and involve many changes in gene expression and metabolic fluxes. Until
      now, plant stress studies have been mainly dealt only with a single stress
      approach. However, plants exposed to multiple stresses at the same time, a
      combinatorial approach reflecting real-world scenarios, show tailored responses
      completely different from the response to the individual stresses, due to the
      stress-related plasticity of plant genome and to specific metabolic
      modifications. In this view, recently it has been found that gamma-aminobutyric
      acid (GABA) but not glycine betaine (GB) is accumulated in durum wheat plants
      under salinity only when it is combined with high nitrate and high light. In
      these conditions, plants show lower reactive oxygen species levels and higher
      photosynthetic efficiency than plants under salinity at low light. This is
      certainly relevant because the most of drought or salinity studies performed on
      cereal seedlings have been done in growth chambers under controlled culture
      conditions and artificial lighting set at low light. However, it is very
      difficult to interpret these data. To unravel the reason of GABA accumulation and
      its possible mode of action, in this review, all possible roles for GABA shunt
      under stress are considered, and an additional mechanism of action triggered by
      salinity and high light suggested.

PMID- 29456549
TI  - Global DNA Methylation in the Chestnut Blight Fungus Cryphonectria parasitica and
      Genome-Wide Changes in DNA Methylation Accompanied with Sectorization.
AB  - Mutation in CpBck1, an ortholog of the cell wall integrity mitogen-activated
      protein kinase kinase kinase (MAPKKK) of Saccharomyces cerevisiae, in the
      chestnut blight fungus Cryphonectria parasitica resulted in a sporadic
      sectorization as culture proceeded. The progeny from the sectored area maintained
      the characteristics of the sector, showing a massive morphogenetic change,
      including robust mycelial growth without differentiation. Epigenetic changes were
      investigated as the genetic mechanism underlying this sectorization.
      Quantification of DNA methylation and whole-genome bisulfite sequencing revealed
      genome-wide DNA methylation of the wild-type at each nucleotide level and changes
      in DNA methylation of the sectored progeny. Compared to the wild-type, the
      sectored progeny exhibited marked genome-wide DNA hypomethylation but increased
      methylation sites. Expression analysis of two DNA methyltransferases, including
      two representative types of DNA methyltransferase (DNMTase), demonstrated that
      both were significantly down-regulated in the sectored progeny. However,
      functional analysis using mutant phenotypes of corresponding DNMTases
      demonstrated that a mutant of CpDmt1, an ortholog of RID of Neurospora crassa,
      resulted in the sectored phenotype but the CpDmt2 mutant did not, suggesting that
      the genetic basis of fungal sectorization is more complex. The present study
      revealed that a mutation in a signaling pathway component resulted in
      sectorization accompanied with changes in genome-wide DNA methylation, which
      suggests that this signal transduction pathway is important for epigenetic
      control of sectorization via regulation of genes involved in DNA methylation.

PMID- 29456550
TI  - Genomic Analysis Revealed New Oncogenic Signatures in TP53-Mutant Hepatocellular
      Carcinoma.
AB  - The TP53 gene is the most commonly mutated gene in human cancers and mutations in
      TP53 have been shown to have either gain-of-function or loss-of-function effects.
      Using the data generated by The Cancer Genome Atlas, we sought to define the
      spectrum of TP53 mutations in hepatocellular carcinomas (HCCs) and their
      association with clinicopathologic features, and to determine the oncogenic and
      mutational signatures in TP53-mutant HCCs. Compared to other cancer types, HCCs
      harbored distinctive mutation hotspots at V157 and R249, whereas common mutation
      hotspots in other cancer types, R175 and R273, were extremely rare in HCCs. In
      terms of clinicopathologic features, in addition to the associations with chronic
      viral infection and high Edmondson grade, we found that TP53 somatic mutations
      were less frequent in HCCs with cholestasis or tumor infiltrating lymphocytes,
      but were more frequent in HCCs displaying necrotic areas. An analysis of the
      oncogenic signatures based on the genetic alterations found in genes recurrently
      altered in HCCs identified four distinct TP53-mutant subsets, three of which were
      defined by CTNNB1 mutations, 1q amplifications or 8q24 amplifications,
      respectively, that co-occurred with TP53 mutations. We also found that mutational
      signature 12, a liver cancer-specific signature characterized by T>C
      substitutions, was prevalent in HCCs with wild-type TP53 or with missense TP53
      mutations, but not in HCCs with deleterious TP53 mutations. Finally, whereas
      patients with HCCs harboring deleterious TP53 mutations had worse overall and
      disease-free survival than patients with TP53-wild-type HCCs, patients with HCCs
      harboring missense TP53 mutations did not have worse prognosis. In conclusion,
      our results highlight the importance to consider the genetic heterogeneity among
      TP53-mutant HCCs in studies of biomarkers and molecular characterization of HCCs.

PMID- 29456551
TI  - Genetic Diversity of the Endangered Neotropical Cichlid Fish (Gymnogeophagus
      setequedas) in Brazil.
AB  - Gymnogeophagus setequedas is a rare and rheophilic species of tribe Geophagini,
      considered endangered in Brazilian red lists. Its previously known geographical
      distribution range was the Parana River basin, in Paraguay, and a tributary of
      the Itaipu Reservoir in Brazil. Since its description no specimens have been
      collected in the original known distribution area. However, recent records of G.
      setequedas in the lower Iguacu River, in a region considered highly endemic for
      the ichthyofauna, extended the known geographical distribution and may represent
      one of the last remnants of the species. The aim of this study was to estimate
      the genetic diversity and population structure of G. setequedas, using
      microsatellite markers and mitochondrial haplotypes, in order to test the
      hypothesis of low genetic diversity in this restricted population. Muscular
      tissue samples of 86 specimens were obtained from nine locations in the Lower
      Iguacu River basin, between upstream of the Iguacu Falls and downstream of the
      Salto Caxias Reservoir. Seven microsatellites loci were examined and a total of
      120 different alleles were obtained. The number of alleles per locus (NA) was
      17.429, effective alleles (NE) 6.644, expected heterozygosity (HE) 0.675,
      observed (HO) heterozygosity 0.592, and inbreeding coefficient (FIS) 0.128.
      Twelve haplotypes in the D-Loop region were revealed, with values of h (0.7642)
      and pi (0.00729), suggesting a large and stable population with a long
      evolutionary history. Thus, both molecular markers revealed high levels of
      genetic diversity and indicated the occurrence of a single G. setequedas
      population distributed along a stretch of approximately 200 km. The pattern of
      mismatch distribution was multimodal, which is usually ascribed to populations in
      demographic equilibrium. Nevertheless, the construction of a new hydroelectric
      power plant, already underway between the Salto Caxias Reservoir and Iguacu
      Falls, could fragment this population, causing loss of genetic diversity and
      population decline, and for this reason it is necessary to maintain the Iguacu
      River tributaries and downstream area from the Lower Iguacu Reservoir free of
      additional dams, to guarantee the survival of this species.

PMID- 29456552
TI  - Identification of Single Nucleotide Non-coding Driver Mutations in Cancer.
AB  - Recent whole-genome sequencing studies have identified millions of somatic
      variants present in tumor samples. Most of these variants reside in non-coding
      regions of the genome potentially affecting transcriptional and post
      transcriptional gene regulation. Although a few hallmark examples of driver
      mutations in non-coding regions have been reported, the functional role of the
      vast majority of somatic non-coding variants remains to be determined. This is
      because the few driver variants in each sample must be distinguished from the
      thousands of passenger variants and because the logic of regulatory element
      function has not yet been fully elucidated. Thus, variants prioritized based on
      mutational burden and location within regulatory elements need to be validated
      experimentally. This is generally achieved by combining assays that measure
      physical binding, such as chromatin immunoprecipitation, with those that
      determine regulatory activity, such as luciferase reporter assays. Here, we
      present an overview of in silico approaches used to prioritize somatic non-coding
      variants and the experimental methods used for functional validation and
      characterization.

PMID- 29456554
TI  - Compound Heterozygous Variants in the Coiled-Coil Domain Containing 40 Gene in a
      Chinese Family with Primary Ciliary Dyskinesia Cause Extreme Phenotypic Diversity
      in Cilia Ultrastructure.
AB  - Purpose: Primary ciliary dyskinesia (PCD) is a rare genetic disorder manifested
      with recurrent infections of respiratory tract and infertility. Mutations in more
      than 20 genes including the Coiled-Coil Domain Containing 40 (CCDC40) gene are
      associated with PCD. A Chinese proband with a clinical diagnosis of PCD was
      analyzed for mutations in these genes to identify the genetic basis of the
      disease in the family. The proband showed altered mucociliary clearance of the
      airways, various degree of hyperemia and edema of the mucous membrane, left/right
      body asymmetry, infertility and ultrastructural abnormality of cilia in both
      sperm and bronchioles. Methods: The DNA from the proband was analyzed for genetic
      variation in a subset of genes known to cause PCD using targeted next generation
      sequencing in order to understand the molecular and genetic basis of the PCD in
      present family. The result of targeted next generation sequencing has been
      validated by Sanger sequencing and q-PCR. Results: Targeted next-generation
      sequencing identified two novel mutations (c.1259delA and EX17_20 deletion) in
      CCDC40 gene that causes abnormal CCDC40 mRNA expression. These two novel variants
      cause disorganization of axoneme filaments, which resulted in reduction of sperm
      motility and phenotypic diversity in ultrastructure of cilia in the proband.
      Conclusion: These findings highlight the significance of the mutations in CCDC40
      as novel candidates for genetic testing in PCD patients as well as the key role
      of ICSI treatment for the families affected by this ciliary dysmotility. Our
      findings showed that our work enriched the performance of cilia ultrastructure
      which were not previously reported in PCD patients.

PMID- 29456553
TI  - Silencing of Iron and Heme-Related Genes Revealed a Paramount Role of Iron in the
      Physiology of the Hematophagous Vector Rhodnius prolixus.
AB  - Iron is an essential element for most organisms However, free iron and heme, its
      complex with protoporphyrin IX, can be extremely cytotoxic, due to the production
      of reactive oxygen species, eventually leading to oxidative stress. Thus,
      eukaryotic cells control iron availability by regulating its transport, storage
      and excretion as well as the biosynthesis and degradation of heme. In the genome
      of Rhodnius prolixus, the vector of Chagas disease, we identified 36 genes
      related to iron and heme metabolism We performed a comprehensive analysis of
      these genes, including identification of homologous genes described in other
      insect genomes. We observed that blood-meal modulates the expression of ferritin,
      Iron Responsive protein (IRP), Heme Oxygenase (HO) and the heme exporter Feline
      Leukemia Virus C Receptor (FLVCR), components of major pathways involved in the
      regulation of iron and heme metabolism, particularly in the posterior midgut
      (PM), where an intense release of free heme occurs during the course of
      digestion. Knockdown of these genes impacted the survival of nymphs and adults,
      as well as molting, oogenesis and embryogenesis at different rates and time
      courses. The silencing of FLVCR caused the highest levels of mortality in nymphs
      and adults and reduced nymph molting. The oogenesis was mildly affected by the
      diminished expression of all of the genes whereas embryogenesis was dramatically
      impaired by the knockdown of ferritin expression. Furthermore, an intense
      production of ROS in the midgut of blood-fed insects occurs when the expression
      of ferritin, but not HO, was inhibited. In this manner, the degradation of
      dietary heme inside the enterocytes may represent an oxidative challenge that is
      counteracted by ferritins, conferring to this protein a major antioxidant role.
      Taken together these results demonstrate that the regulation of iron and heme
      metabolism is of paramount importance for R. prolixus physiology and imbalances
      in the levels of these key proteins after a blood- meal can be extremely
      deleterious to the insects in their various stages of development.

PMID- 29456555
TI  - A Bootstrap Based Measure Robust to the Choice of Normalization Methods for
      Detecting Rhythmic Features in High Dimensional Data.
AB  - Motivation: Gene-expression data obtained from high throughput technologies are
      subject to various sources of noise and accordingly the raw data are pre
      processed before formally analyzed. Normalization of the data is a key pre
      processing step, since it removes systematic variations across arrays. There are
      numerous normalization methods available in the literature. Based on our
      experience, in the context of oscillatory systems, such as cell-cycle, circadian
      clock, etc., the choice of the normalization method may substantially impact the
      determination of a gene to be rhythmic. Thus rhythmicity of a gene can purely be
      an artifact of how the data were normalized. Since the determination of rhythmic
      genes is an important component of modern toxicological and pharmacological
      studies, it is important to determine truly rhythmic genes that are robust to the
      choice of a normalization method. Results: In this paper we introduce a
      rhythmicity measure and a bootstrap methodology to detect rhythmic genes in an
      oscillatory system. Although the proposed methodology can be used for any high
      throughput gene expression data, in this paper we illustrate the proposed
      methodology using several publicly available circadian clock microarray gene
      expression datasets. We demonstrate that the choice of normalization method has
      very little effect on the proposed methodology. Specifically, for any pair of
      normalization methods considered in this paper, the resulting values of the
      rhythmicity measure are highly correlated. Thus it suggests that the proposed
      measure is robust to the choice of a normalization method. Consequently, the
      rhythmicity of a gene is potentially not a mere artifact of the normalization
      method used. Lastly, as demonstrated in the paper, the proposed bootstrap
      methodology can also be used for simulating data for genes participating in an
      oscillatory system using a reference dataset. Availability: A user friendly code
      implemented in R language can be downloaded from
      http://www.eio.uva.es/~miguel/robustdetectionprocedure.html.

PMID- 29456556
TI  - Human Umbilical Cord Wharton Jelly-Derived Adult Mesenchymal Stem Cells, in
      Biohybrid Scaffolds, for Experimental Skin Regeneration.
AB  - The ultimate goal for skin tissue engineering is to regenerate skin lesions to
      allow the full restoration of morphological and functional properties as what
      they were before injury. To this end, we have assembled a new prototype of a
      biomimetic human umbilical cord adult mesenchymal stem cell (hUCMS)/fibrin-based
      scaffold. We have fully characterized the proposed dermal equivalent (DE) in
      vitro, to assess morphological, functional, and biological properties of the
      encased cells. We transplanted DE subcutaneously into immunocompetent rodents, to
      verify its full biocompatibility. Finally, we studied DE graft effects on full
      thickness wounds, in immunocompetent mice to demonstrate its capability to drive
      the healing process in the absence of significant scarring tissue. The excellent
      outcome of these in vivo studies fuels hope that this new approach, based on a
      biohybrid DE, may be applied to the operative treatment of skin lesions (i.e.,
      diabetic foot ulcers and burns) in man.

PMID- 29456559
TI  - Information on vaccination safety on internet.

PMID- 29456558
TI  - Prevalence of lymph node and maximum short axis in traumatic patients.
AB  - Background: Normal size of mesenteric lymph nodes has not been well evaluated, as
      these lymph nodes are small but may be seen frequently in computed tomography
      (CT). The aim of this study is to determine the prevalence of mesenteric lymph
      nodes at root of mesentery and mesentery itself. Materials and Methods: This is a
      cross-sectional study on traumatic patients with normal multidetector CT (MDCT)
      referred to Al-Zahra Hospital in 2014-2016. The largest short axis of lymph nodes
      was recorded. Their location was divided into three groups of mesenteric root,
      peripheral mesentery, and mesentery of the right lower quadrant (RLQ). Size and
      number of lymph nodes in terms of locations were recorded. A number of more than
      6 nodes in a position was defined as cluster nodes. Data were analyzed using SPSS
      software version 20. P < 0.05 was considered statistically significant. Results:
      Four hundred traumatic patients underwent MDCT scanning. The mean age of these
      patients was 36.6 +/- 13.4 years. The number of lymph nodes was <3 in 49.3%,
      52.5%, and 52.2%; 3-6 in 45.8%, 42.8%, and 42.8%; >6 in 5%, 4.8%, and 4.8% of
      central, peripheral, and RLQ mesentery, respectively. The average size of largest
      central, peripheral, and RLQ lymph nodes was 4.53 +/- 1.33, 4.37 +/- 1.68, and
      4.37 +/- 1.68, respectively (P = 0.64). Largest size of short axis in patients
      with cluster lymph nodes was significantly more than noncluster nodes (P < 0.001
      for all regions). Conclusion: Mean size of mesenteric lymph nodes was similar to
      the previous study, but the largest nodes were considerably larger. Furthermore,
      largest short axis of cluster nodes was significantly more than noncluster ones.

PMID- 29456557
TI  - The altered expression of perineuronal net elements during neural
      differentiation.
AB  - Background: Perineuronal nets (PNNs), which are localized around neurons during
      development, are specialized forms of neural extracellular matrix with
      neuroprotective and plasticity-regulating roles. Hyaluronan and proteoglycan link
      protein 1 (HAPLN1), tenascin-R (TNR) and aggrecan (ACAN) are key elements of
      PNNs. In diseases characterized by neuritogenesis defects, the expression of
      these proteins is known to be downregulated, suggesting that PNNs may have a role
      in neural differentiation. Methods: In this study, the mRNA and protein levels of
      HAPLN1, TNR and ACAN were determined and compared at specific time points of
      neural differentiation. We used PC12 cells as the in vitro model because they
      reflect this developmental process. Results: On day 7, the HAPLN1 mRNA level
      showed a 2.9-fold increase compared to the non-differentiated state. However, the
      cellular HAPLN1 protein level showed a decrease, indicating that the protein may
      have roles in neural differentiation, and may be secreted during the early period
      of differentiation. By contrast, TNR mRNA and protein levels remained unchanged,
      and the amount of cellular ACAN protein showed a 3.7-fold increase at day 7.
      These results suggest that ACAN may be secreted after day 7, possibly due to its
      large amount of post-translational modifications. Conclusions: Our results
      provide preliminary data on the expression of PNN elements during neural
      differentiation. Further investigations will be performed on the role of these
      elements in neurological disease models.

PMID- 29456560
TI  - The effect of testosterone gel on fertility outcomes in women with a poor
      response in in vitro fertilization cycles: A pilot randomized clinical trial.
AB  - Background: In this study, the effect of testosterone gel administration during
      ovulation induction on the fertility rate was examined in women with a poor
      ovarian response in in vitro fertilization (IVF) cycles. Materials and Methods:
      The current study is a single-blinded, randomized clinical trial. Patients who
      met inclusion (Bologna) criteria were placed in the antagonist cycle group. The
      patients were randomly divided into two groups each included 25 participants
      treated with a placebo (lubricant gel, the controls) and testosterone gel
      (intervention). Fertility outcomes were compared between two study groups.
      Results: The mean +/- standard deviation (SD) age of intervention (41.04 +/-
      3.77) versus control group (39.69 +/- 3.29) was not statistically different. The
      two studied groups were not statistically different in terms of follicle
      stimulating hormone; antral follicle count, IVF, anti-Mullerian hormone, and the
      duration of infertility. The mean +/- SD of oocyte 2.48 +/- 1.64 versus 1.17 +/-
      1.27 and embryo 1.60 +/- 1.58 versus 0.39 +/- 0.58 in intervention group was
      significantly higher than control group (P < 0.01). The rate of pregnancy 16%
      versus 0% and embryo of quality A-B was significantly higher in intervention
      group than control (60% versus 17.4%, P < 0.05). Conclusion: The results of the
      current study showed that the testosterone gel has a significant impact on the
      fertility rate in women with a poor response in the IVF cycles. Further,
      randomized clinical trials with larger sample sized are recommended.

PMID- 29456561
TI  - Evaluation of observed and the expected incidence of common cancers: An
      experience from Southwestern of Iran, 2010-2014.
AB  - Background: Awareness of observed and expected incidence of cancers is so
      important in managing cancer as the third mortality cause in Iran. In the present
      study, we evaluated observed and the expected incidence of common cancers in
      Chaharmahal and Bakhtiari province. Materials and Methods: This study is a
      Secondary data analysis. All data about pathology-based cancer registration
      (Cancer diagnosis was based on pathological laboratory, ICD-O2) in Chaharmahal
      and Bakhtiari in Southwestern Iran in 2010-2014 was used. By dividing the number
      of registered cases of each cancer in every age group into the total observed
      cancers in that age group, the observed ratio of each cancer in that age group
      was calculated. Then, using the proposed coefficients Parkin and age-standardized
      cancer ratio method, the expected ratios in each age group, were calculated.
      Results: In 5 years study, 2918 new cases of cancer were recorded. Out of them,
      1735 (59.46%) were male. The annual average total occurrence of all cancers in
      this province was 68.2/100,000 populations. The observed incidence ratios of
      common cancers, including stomach, breast, colorectal, thyroid, lymph nodes,
      ovaries, gall bladder, the bladder and the brain, were 0.11, 0.12, 0.09, 0.06,
      0.02, 0.03, 0.01, 0.08, and 0.05, respectively. The expected incidence ratios of
      above-mentioned cancers are 0.11, 0.13, 0.1, 0.06, 0.02, 0.03, 0.01, 0.08, and
      0.05, respectively. Based on observed (O) and expected (E) comparison, breast and
      colorectal cancer had higher incidence than expected ratio. Conclusion: Our
      results showed that in our area, treatment programs and health plans should focus
      on cancer registration, especially on common cancers and reevaluate breast and
      colorectal cancer occurrence. Therefore, the plan for the control and prevention
      of this cancer must be a high priority for health policymakers.

PMID- 29456562
TI  - Colonization with hospital flora and its associated risk factors in neonates
      hospitalized in neonatal ward of a teaching center in Isfahan, Iran.
AB  - Background: Due to the high incidence and prevalence of infection in neonatal
      ward, especially Neonatal Intensive Care Units (NICUs) reported by different
      studies and the important role of colonization with hospital germs in the
      development of nosocomial infections, we intended to evaluate the risk of
      colonization with hospital germs in neonates and its associated risk factors.
      Materials and Methods: This cross-sectional, descriptive-analytical study was
      conducted in 2016 in a Teaching Center in Iran. In total, 51 neonates were
      selected based on the inclusion criteria, and after recording their information
      in a checklist, samples were taken by swab from outer ear, axilla, and groin for
      culture. Neonates with negative culture from mentioned regions were enrolled in
      the study. The swab samples again were taken and sent for culture from mentioned
      regions in at least 3 days after hospitalization. Culture results from first and
      second sampling were collected and analyzed statistically. Results: This study
      was conducted on 51 neonates. The mean gestational age among the neonates ranged
      from 35.25 (Week) +/- 2.98. 22 girls (43.1%) and 29 boys (56.9%), most of them
      were born by cesarean. Based on the results of logistic regression, a significant
      association was found between the occurrence of colonization of hospital flora
      and the place hospitalization of the newborns (odds ratio (OR): 4.750; 95%
      confidence interval (CI): 1.26-17.85). Conclusion: This study revealed that the
      only risk factors of colonization with hospital flora in neonates are the type of
      delivery and place of hospitalization. Based on findings of the study, it is
      recommended to focus on efforts in increasing the rate of natural birth as well
      as improving conditions of infection control in NICUs to reduce the number of
      incidences of colonization with hospital flora in neonates.

PMID- 29456563
TI  - Does topical tranexamic acid reduce postcoronary artery bypass graft bleeding?
AB  - Background: Postoperative bleeding is a common problem in cardiac surgery. We
      tried to evaluate the effect of topical tranexamic acid (TA) on reducing
      postoperative bleeding of patients undergoing on-pump coronary artery bypass
      graft (CABG) surgery. Materials and Methods: One hundred and twenty-six isolated
      primary CABG patients were included in this clinical trial. They were divided
      blindly into two groups; Group 1, patients receiving 1 g TA diluted in 100 ml
      normal saline poured into mediastinal cavity before closing the chest and Group
      2, patients receiving 100 ml normal saline at the end of operation. First 24 and
      48 h chest tube drainage, hemoglobin decrease and packed RBC transfusion needs
      were compared. Results: Both groups were the same in baseline characteristics
      including gender, age, body mass index, ejection fraction, clamp time, bypass
      time, and operation length. During the first 24 h postoperatively, mean chest
      tube drainage in intervention group was 567 ml compared to 564 ml in control
      group (P = 0.89). Mean total chest tube drainage was 780 ml in intervention group
      and 715 ml in control group (P = 0.27). There was no significant difference in
      both mean hemoglobin decrease (P = 0.26) and packed RBC transfusion (P = 0.7).
      Topical application of 1 g TA diluted in 100 ml normal saline does not reduce
      postoperative bleeding of isolated on-pump CABG surgery. Conclusion: We do not
      recommend topical usage of 1 g TA diluted in 100 ml normal saline for decreasing
      blood loss in on-pump CABG patients.

PMID- 29456564
TI  - Role of granulocyte colony-stimulating factor in human reproduction.
AB  - As new research reveals, granulocyte colony-stimulating factor (G-CSF) plays an
      effective role in pregnancy success, considering that it not only affects the
      embryo implantation and ovarian function but also it promotes endometrial
      thickening and improves the pathophysiology of endometriosis, which all
      fundamentally lead to reducing pregnancy loss. In this review, we focus on the
      role of G-CSF in human reproduction. We summarized its role in ovulation,
      luteinized unruptured follicle syndrome, poor responders, improving repeated in
      vitro fertilization failure, endometrial receptivity and treatment of thin
      endometrium, and recurrent spontaneous abortion.

PMID- 29456565
TI  - Prevalence of peptic ulcer in Iran: Systematic review and meta-analysis methods.
AB  - Background: Peptic ulcer is a prevalent problem and symptoms include epigastria
      pain and heartburn. This study aimed at investigating the prevalence and causes
      of peptic ulcers in Iran using systematic review and meta-analysis. Materials and
      Methods: Eleven Iranian papers published from 2002 to 2016 are selected using
      valid keywords in the SID, Goggle scholar, PubMed and Elsevier databases. Results
      of studies pooled using random effects model in meta-analysis. The heterogeneity
      of the sample was checked using Q test and I2 index. Results: Total sample size
      in this study consist of 1335 individuals with peptic ulcer (121 samples per
      article). The prevalence of peptic ulcers was estimated 34% (95% CI= 0.25 -
      0.43). The prevalence of peptic ulcers was 30% and 60% in woman and man
      respectively. The highest environmental factor (cigarette) has been addressed in
      30% (95% CI= 0.23-0.37) of patients. The prevalence of Helicobacter pylori was
      estimated in 62% (95% CI= 0.49-0.75) of patients. Conclusion: The results of this
      study show that prevalence of peptic ulcers in Iran (34%) is higher that
      worldwide rate (6% to 15%). There was an increasing trend in the prevalence of
      peptic ulcer over a decade from 2002 to 2016.

PMID- 29456566
TI  - Is application of Kinesio tape to treat hyperlordosis more effective on abdominal
      muscles or hamstrings?
AB  - Background: Hyperlordosis is defined as an abnormal increase in the lumbar arch
      of >40 degrees . This study compared two taping techniques include abdominal
      muscles and hamstrings taping for the treatment of lumbar hyperlordosis.
      Materials and Methods: The randomized clinical trial was performed in Shiraz,
      Iran, during June and September 2014. Thirty women aged 20-45 years old with at
      least 40 degrees  lumbar lordosis participated. The women were randomized into
      two groups (n = 15). Abdominal muscles taping was performed for the first group,
      whereas the other group underwent hamstrings taping with 30% tension. Lumbar
      lordosis was measured before, immediately after, and 24 h after taping. The two
      way repeated measures analysis of variance was used to compare the two groups for
      lumbar lordosis angle. Results: No significant differences were detected between
      the lumbar lordosis angles before and immediately after taping in the two groups
      (P > 0.05). However, a significant reduction was observed in lordosis angle in
      the abdominal group and the hamstring group 24 h after taping relative to before
      intervention (P < 0.01). Conclusion: Taping of the abdominal and hamstring
      muscles was not effective immediately, whereas it decreased lordosis after 24 h.

PMID- 29456567
TI  - Influence of blood glucose level on the prognosis of patients with diabetes
      mellitus complicated with ischemic stroke.
AB  - We carried out this meta-analysis for the aim of exploring the influence of
      diabetes mellitus (DM) on the prognosis of patients with ischemic stroke.
      Relevant studies were identified using computerized databases supplemented with
      manual search strategies. The included studies were strictly followed the
      inclusion and exclusion criteria. Case-control studies which related to the
      influence of DM on the prognosis of patients with ischemic stroke were selected.
      Statistical analyses were implemented with the STATA version 12.0 statistical
      software. Our current meta-analysis initially retrieved 253 studies (227 in
      Chinese and 26 in English), 13 studies (6 in English and 7 in Chinese) were
      eventually incorporated in this meta-analysis. These 13 case-control studies
      included 8463 patients altogether (3249 patients with DM complicated with
      ischemic stroke and 5214 patients with ischemic stroke). The results of this meta
      analysis manifested that there was a significant difference of the blood glucose
      level at 48 h after stroke between patients with DM complicated with ischemic
      stroke and patients with ischemic stroke (standard mean difference [SMD] =1.27,
      95% confidence interval [CI] =0.02-2.51, P = 0.047); however, the effectiveness,
      fatality, and the National Institutes of Health Stroke Scale (NIHSS) score in
      patients with DM complicated with ischemic stroke, and patients with ischemic
      stroke had no significant difference (effectiveness: risk ratio [RR] = 0.88, 95%
      CI = 0.75-1.03, P = 0.121; fatality: RR = 1.29, 95% CI = 0.97-1.71, P = 0.081;
      NIHSS score: SMD = -0.14, 95% CI = -1.56-1.28, P = 0.849). The current evidence
      suggests that there is statistical difference of the blood glucose level at 48 h
      after stroke between patients with DM complicated with ischemic stroke and
      patients with ischemic stroke, but there is no statistical difference of
      prognostic indicators between patients in two groups. Thus, our study provides
      certain clinical value.

PMID- 29456569
TI  - Use of Western Medicine and Traditional Korean Medicine for Joint Disorders: A
      Retrospective Comparative Analysis Based on Korean Nationwide Insurance Data.
AB  - This study aimed to compare the usage of Western medicine and traditional Korean
      medicine for treating joint disorders in Korea. Data of claims from all medical
      institutions with billing statements filed to HIRA from 2011 to 2014 for the four
      most frequent joint disorders were used for the analysis. Data from a total of
      1,100,018 patients who received medical services from 2011 to 2014 were analyzed.
      Descriptive statistics are presented as type of care and hospital type. All
      statistical analyses were performed using IBM SPSS for Windows version 21. Of the
      1,100,018 patients with joint disorders, 456,642 (41.5%) were males and 643,376
      (58.5%) were females. Per diem costs of hospitalization in Western medicine
      clinics and traditional Korean medicine clinics were approximately 160,000 KRW
      and 50,000 KRW, respectively. Among costs associated with Western medicine,
      physiotherapy cost had the largest proportion (28.78%). Among costs associated
      with traditional Korean medicine, procedural costs and treatment accounted for
      more than 70%, followed by doctors' fees (21.54%). There were distinct
      differences in patterns of medical care use and cost of joint disorders at the
      national level in Korea. This study is expected to contribute to management
      decisions for musculoskeletal disease involving joint disorders.

PMID- 29456570
TI  - Use of Chinese Medicine Reduces the Development of Cervical Cancer from Pap Smear
      Diagnosed Cervical Dysplasia: A Case-Control Study.
AB  - The Pap test diagnosed cervical dysplasia, which could recover to normal or
      progress to cervical cancer (CC), is an early stage of cell abnormality before
      CC. This case-control study analyzed the differences in the risk to develop CC
      between Chinese medicine (CM) users and nonusers among women who had ever been
      diagnosed as having cervical dysplasia. A total of 750 CC patients with a
      cervical dysplasia history were collected between 1998 and 2011 from National
      Health Insurance Research Database, and controls were women with cervical
      dysplasia history but did not develop CC. Adjusted odds ratio (aOR) for
      developing CC was assessed using multivariable logistic regression after
      adjusting for age, urbanization of residence, and occupation. The proportion of
      using CM among CC patients was lower than that among CC nonpatients, with an aOR
      of 0.8. By analyzing the relationship between CC development and the frequency of
      CM usage, the trend test revealed a significant decreasing trend for developing
      CC among high-frequency CM users. Moreover, the most frequently used single herb
      high-frequency was Rheum palmatum (Da-Huang). The usage of CM might be an
      effective complementary method to prevent uterine cervix from progressing to CC
      after cervical dysplasia has occurred.

PMID- 29456568
TI  - Harnessing the immune system in the battle against breast cancer.
AB  - Breast cancer is the most prevalent malignancy in women and the second most
      common cause of cancer-related death worldwide. Despite major innovations in
      early detection and advanced therapeutics, up to 30% of women with node-negative
      breast cancer and 70% of women with node-positive breast cancer will develop
      recurrence. The recognition that breast tumors are infiltrated by a complex array
      of immune cells that influence their development, progression, and metastasis, as
      well as their responsiveness to systemic therapies has sparked major interest in
      the development of immunotherapies. In fact, not only the native host immune
      system can be altered to promote potent antitumor response, but also its
      components can be manipulated to generate effective therapeutic strategies. We
      present here a review of the major approaches to immunotherapy in breast cancers,
      both successes and failures, as well as new therapies on the horizon.

PMID- 29456571
TI  - Resveratrol Ameliorates Experimental Alcoholic Liver Disease by Modulating
      Oxidative Stress.
AB  - The aim of this study was to investigate the hepatoprotective effects of
      resveratrol in alcoholic liver disease (ALD). Alcohol was administered to healthy
      female rats starting from 6% (v/v) and gradually increased to 20% (v/v) by the
      fifth week. After 16 weeks of intervention, liver enzymes (aspartate
      aminotransferase [AST] and alanine aminotransferase [ALT]) were analyzed using a
      chemistry analyzer, while hepatic antioxidant enzymes, oxidative stress markers,
      and caspase 3 activity were assessed using ELISA kits. Furthermore, hepatic
      CYP2E1 protein levels and mRNA levels of antioxidant and inflammation-related
      genes were determined using western blotting and RT-PCR, respectively. The
      results showed that resveratrol significantly attenuated alcohol-induced
      elevation of liver enzymes and improved hepatic antioxidant enzymes. Resveratrol
      also attenuated alcohol-induced CYP2E1 increase, oxidative stress, and apoptosis
      (caspase 3 activity). Moreover, genes associated with oxidative stress and
      inflammation were regulated by resveratrol supplementation. Taken together, the
      results suggested that resveratrol alleviated ALD through regulation of oxidative
      stress, apoptosis, and inflammation, which was mediated at the transcriptional
      level. The data suggests that resveratrol is a promising natural therapeutic
      agent against chronic ALD.

PMID- 29456573
TI  - Pharmacological Effect of Caulophyllum robustum on Collagen-Induced Arthritis and
      Regulation of Nitric Oxide, NF-kappaB, and Proinflammatory Cytokines In Vivo and
      In Vitro.
AB  - Caulophyllum robustum Maxim (C. robustum) has commonly been used as traditional
      Chinese medicine for the treatment of rheumatic pain and rheumatoid arthritis
      (RA) in China. This paper first investigated the anti-inflammation effect of C.
      robustum extraction (CRME) on RAW264.7 cells stimulated by lipopolysaccharide
      (LPS) and gene expression levels of inflammatory factors. Moreover, we first
      evaluated the anti-RA effects of CRME using collagen-induced arthritis (CIA) in
      DBA/1J mice, and the incidence, clinical score, and joint histopathology were
      evaluated. The levels of IL-1, IL-6, TNF-alpha, and PGE2 inflammatory factors in
      sera of mice were detected by enzyme-linked immunosorbent assay. The expression
      of NF-kappaB p65 in the joint was tested by immune histochemical technique. The
      results showed that, compared with the model group, CRME significantly improved
      symptoms of the arthritis index, limb swelling, and histological findings by
      decreasing synovial membrane damage, the extent of inflammatory cell
      infiltration, and the expansion of capillaries in CIA mice. The results also
      showed that CRME can reduce the levels of IL-1, IL-6, TNF-alpha, and PGE2 and
      inhibit the expression of NF-kappaB p65. All these results indicated the anti
      inflammatory efficacy of CRME as a novel botanical extraction for the treatment
      of RA.

PMID- 29456572
TI  - A Review on Ethnopharmacological Applications, Pharmacological Activities, and
      Bioactive Compounds of Mangifera indica (Mango).
AB  - Mangifera indica (family Anacardiaceae), commonly known as mango, is a
      pharmacologically, ethnomedically, and phytochemically diverse plant. Various
      parts of M. indica tree have been used in traditional medicine for the treatment
      of different ailments, and a number of bioactive phytochemical constituents of M.
      indica have been reported, namely, polyphenols, terpenes, sterols, carotenoids,
      vitamins, and amino acids, and so forth. Several studies have proven the
      pharmacological potential of different parts of mango trees such as leaves, bark,
      fruit peel and flesh, roots, and flowers as anticancer, anti-inflammatory,
      antidiabetic, antioxidant, antibacterial, antifungal, anthelmintic,
      gastroprotective, hepatoprotective, immunomodulatory, antiplasmodial, and
      antihyperlipemic. In the present review, a comprehensive study on
      ethnopharmacological applications, pharmacological activities, and bioactive
      compounds of M. indica has been described.

PMID- 29456574
TI  - The Root Aqueous Extract of Entada africana Guill. et Perr. (Mimosaceae) Inhibits
      Implant Growth, Alleviates Dysmenorrhea, and Restores Ovarian Dynamic in a Rat
      Model of Endometriosis.
AB  - Entada africana (Mimosaceae) was reported to have analgesic and antioxidant
      properties. The present study is aimed at investigating the effects of the root
      aqueous extract of Entada africana (EA) on an experimental model of
      endometriosis. The study was performed in rats orally treated with EA at doses of
      127.5, 255, and 510 mg/kg. Microgynon(r) 30 served as the reference substance.
      Estradiol valerate and oxytocin were used to induce dysmenorrhea. Endometrial
      implant levels of catalase and malondialdehyde (MDA) allowed estimating tissue
      oxidative status. Ovarian dynamic and rat sexual behavior were assessed through
      histological analysis of ovaries, uterus, and vagina. EA decreased dysmenorrhea
      at tested doses following a 7-day treatment (p < 0.001). Endometrial implant
      volume decreased following the three treatment periods (p < 0.05). Catalase
      activity (p < 0.001) and MDA level (p < 0.01) increased only following a 3-day
      treatment. EA also increased antral follicles, reduced luteinized unruptured
      follicle number (p < 0.001), and induced animals to be in the estrus phase. In
      conclusion, EA prevented the progress of endometriosis, reduced dysmenorrhea,
      promoted ovarian follicle growth, prevented anovulation, and stimulated the
      special period of rat sexual desire. These results suggest that Entada africana
      could be a promising alternative option for the treatment of endometriosis.

PMID- 29456576
TI  - Editorial.

PMID- 29456575
TI  - Integrative Approach to Facilitate Fracture Healing: Topical Chinese Herbal Paste
      with Oral Strontium Ranelate.
AB  - Strontium ranelate (SrR) is one of the pharmaceutical agents reported to be
      effective on the promotion of fracture healing. This study aimed to evaluate the
      integrative effect of the oral SrR with a topical Chinese herbal paste, namely,
      CDR, on facilitation of bone healing. The in vivo efficacy was evaluated using
      rats with tibial fracture. They were treated with either CDR topically, or SrR
      orally, or their combined treatments. The in vivo results illustrated a
      significant additive effect of CDR on SrR in increasing the yield load of the
      fractured tibia. The in vitro results showed that neither SrR nor CDR exhibited a
      cytotoxic effect on UMR106 and bone-marrow stem cell (BMSC), but both of them
      increased the proliferation of BMSC at low concentrations. The combination of CDR
      at 200 MUg/mL with SrR at 200 or 400 MUg/ml also showed an additive effect on
      increasing the ALP activity of BMSC. Both SrR and CDR alone reduced osteoclast
      formation, and the effective concentration of SrR to inhibit osteoclastogenesis
      was reduced in the presence of CDR. This integrative approach by combining oral
      SrR and topical CDR is effective in promoting fracture healing properly due to
      their additive effects on proosteogenic and antiosteoclastogenic properties.

PMID- 29456577
TI  - Is ultrasound screening for vasa praevia clinically justified and a financially
      viable screening test? A literature review.
AB  - Vasa praevia is an obstetric complication currently not screened for within the
      United Kingdom, which if undetected prenatally can lead to fetal death when the
      membranes rupture. Internationally, guidelines are available providing guidance
      on the best screening policy and management pathways. However, the UK National
      Screening Committee and Royal College of Obstetricians and Gynaecologists do not
      support screening due to a lack of evidence. Recent studies explore the ability
      of ultrasound to detect vasa praevia prenatally in both the general and high-risk
      populations. Whilst there is no consensus on the 'best' screening strategy, the
      majority of authors note that targeted screening of the high-risk population is
      the most achievable and cost-effective strategy. Although not infallible, a
      standard screening protocol could identify the majority of cases in the high-risk
      group. Introduction of a screening strategy would affect training needs of
      professionals within the UK and would have implications on the need to produce
      guidelines on management and quality assurance. Further research is also needed
      to define a relevant high-risk population and explore how this would impact on
      service provision. This review explores the current evidence base for systematic
      screening and the implications for service.

PMID- 29456578
TI  - Sonographic parameters for diagnosing fetal head engagement during labour.
AB  - The purpose of this study was to investigate the diagnostic performance of the
      head-perineum distance, angle of progression, and the head-symphysis distance as
      intrapartum ultrasound parameters in the determination of an engaged fetal head.
      Two hundred and one women in labour underwent both ultrasound and digital vaginal
      examination in the estimation of fetal head station. The transperineal ultrasound
      measured head-perineum distance, angle of progression, and head-symphysis
      distance for values correlating with digital vaginal examination head station.
      Using station 0 as the minimum level of head engagement, correlating cut-off
      values for head-perineum distance, angle of progression, and head-symphysis
      distance were obtained. Receiver operating characteristics were used in
      determining the diagnostic performance of these cut-off values for the detection
      of fetal head engagement. With head-perineum distance of 3.6 cm the sensitivity
      and specificity of sonographic determination of engaged fetal head were 78.7 and
      72.3%, respectively. A head-symphysis distance of 2.8 cm also had sensitivity and
      specificity of 74.5 and 70.8%, respectively, in determining engagement, whilst an
      angle of progression of 101 degrees  was consistent with engagement by digital
      vaginal examination with 68.1% sensitivity and 68.2% specificity. Ultrasound
      shows high diagnostic performance in determining engaged fetal head at a head
      perineum distance of <=3.6 cm, head-symphysis distance of <=2.8 cm, and angle of
      progression of >= 101 degrees .

PMID- 29456579
TI  - Splenic cyst as a rare cause of fetal abdominal cystic mass: A multicenter series
      of nine cases and review of the literature.
AB  - Introduction: Congenital splenic cysts are a rare cause of abdominal cystic
      masses in the fetus. We describe nine cases of this condition, the largest
      reported experience to date. A review of the literature for similar cases was
      also performed. Methods: Cases of congenital splenic cyst were collected from
      three prenatal diagnostic centers and from a dedicated website of prenatal
      diagnosis. Information regarding clinical and sonographic findings was obtained
      by reviewing ultrasound reports and medical records. An electronic search of the
      Pubmed/MEDLINE database for similar cases, with subsequent manual cross
      referencing, was performed and the relevant information from the articles was
      retrieved. Results: A total of nine cases were added to the currently existing
      literature of 32 cases. In all but one of our cases, the prenatal detection of
      the splenic cyst was made in the third trimester, with a median gestational age
      at diagnosis of 30 weeks (range 22-37). The splenic cyst was confirmed after
      delivery in all but one case, which was lost to follow up. Postnatal sonographic
      examinations performed in the remaining eight cases showed that the cyst
      increased in size in two (25%), was stable in size in one (12%), decreased in
      size in one (12%), and completely regressed in the other four cases (50%). No
      complications associated with the cysts were reported in the infants.
      Conclusions: Congenital splenic cyst appears to be a benign condition with no
      known risk of perinatal complications. Nevertheless, differential diagnosis with
      other fetal cystic masses of the left upper abdominal quadrant and postnatal
      sonographic follow up to monitor the size of the cyst are important issues to be
      considered in the perinatal management of these cases.

PMID- 29456580
TI  - The accuracy of ultrasound estimation of fetal weight in comparison to birth
      weight: A systematic review.
AB  - Ultrasound estimation of fetal weight is a highly influential factor in antenatal
      management, guiding both the timing and mode of delivery of a pregnancy. Although
      substantial research has investigated the most accurate ultrasound formula for
      calculating estimated fetal weight, current evidence indicates significant error
      levels. The aim of this systematic review was to identify the most accurate
      method, whilst identifying sources of inaccuracy in order to facilitate
      recommendations for future practice. Seven studies met the inclusion criteria and
      11 different formulae were assessed; ultrasound calculation of fetal weight was
      most commonly overestimated. The Hadlock A formula produced the most accurate
      results, with the lowest levels of random error. Methods incorporating just two
      measurement parameters were inconsistent, producing large random errors across
      multiple studies. Key sources of inaccuracy included difficulties obtaining
      accurate fetal measurements in late gestation; the remainder were operator
      dependent, including lack of experience and insufficient training and audit. The
      accuracy of ultrasound estimated fetal weight has improved in the last decade,
      though a lack of consistency remains evident. National implementation of a
      rigorous audit programme would likely improve accuracy further, and increase the
      confidence and clinical value of the method.

PMID- 29456582
TI  - Assessing the accuracy of ultrasound estimation of gestational age during routine
      antenatal care in in vitro fertilization (IVF) pregnancies.
AB  - Introduction: In the UK an accurate gestational age is confirmed by ultrasound
      measured foetal crown rump length (CRL) at 11 + 2-14 + 1 weeks of gestation. The
      currently recommended Robinson and Fleming crown rump length reference chart was
      develop in 1975. Advances in ultrasound technology and standardized crown rump
      length measurement training could mean this is now out of date. Our study aimed
      to assess its accuracy in current routine antenatal care. Methods: Retrospective
      data from 178 IVF pregnancies seen for routine antenatal care at a UK Regional
      Maternity Unit between 1 January 2006 and 1 January 2016 was retrieved. We
      compared ultrasound calculated crown rump length gestational age taken at the
      routine First Trimester Screening Clinic (FTSC) with the 'true' gestational age
      calculated from the known IVF fertilization date. Results: We identified a
      systematic overestimation of gestational age by ultrasound using the currently
      recommended crown rump length reference chart when compared to IVF gestational
      age. The mean overestimation was 3.0 days (95% CI: 2.7 to 3.4), p < 0.001. A
      range of alternative ultrasound reference charts also generated a systematic
      overestimation, ranging from 1.6 to 2.9 days (p < 0.001, for each). Conclusions:
      The current crown rump length reference chart systematically overestimates
      gestational age by an average of three days when assessed in IVF pregnancies. A
      systematic overestimation was also identified in alternative crown rump length
      reference charts. These differences, although slight, were systematic with
      implications for the accuracy of gestational age estimation particularly in
      pregnancies at risk of pre-term delivery or growth restriction. Our findings need
      confirming in larger, non IVF cohorts and could lead to the need for an updated
      crown rump length reference chart.

PMID- 29456581
TI  - Antenatal diagnosis of total anomalous pulmonary venous connection in functional
      single ventricle hearts: Outcomes over 13-year period.
AB  - Introduction: A functionally single cardiac ventricle seen on foetal ultrasound
      scan carries a guarded prognosis. The antenatal diagnosis of anomalous pulmonary
      venous connection (APVC) remains challenging, if there is no associated
      structural cardiac abnormality. Antenatally, a combination of complex cardiac
      anomaly with suspected isomerism should raise the possibility of associated total
      anomalous pulmonary venous connection (TAPVC). There needs to be a high index of
      suspicion for TAPVC, in functional single ventricle and suspected isomerism, as
      this carries a very grim outcome postnatally. We illustrate foetal
      echocardiographic findings of suspected TAPVC and review outcomes of antenatal
      versus postnatal diagnosis of TAPVC with functional single ventricle. Methods: We
      retrospectively reviewed our database over 13 years, focusing on foetal cardiac
      diagnosis, pregnancy outcomes, management and outcomes of livebirths with
      diagnosis of TAPVC with functional single ventricle. Results: Thirteen patients
      were included in the review. For the nine antenatal patients, three pregnancies
      were terminated and six babies were born alive (four babies had compassionate
      care, two babies had cardiac surgery). One baby is alive at 8.5 years, after
      Fontan surgery. For the four postnatal patients, three babies had compassionate
      care (one alive at age 8.1 years) and one baby had cardiac surgery (died age nine
      weeks). Ten of the 13 patients have right atrial isomerism. Of these 10 patients,
      only two are alive. For the three non-isomeric babies, only one baby is still
      alive. There is heterogeneity of the type of TAPVC diagnosed with no particular
      group that offered better survival. Conclusion: Antenatal diagnosis of TAPVC,
      even in the context of functional single ventricle remains challenging. If
      isomerism is suspected, targeted evaluation of pulmonary venous connection should
      be done. This combination of cardiac lesion carries a very grim outcome. The
      ability to make this diagnosis antenatally will add to the information and
      counselling given to these parents.

PMID- 29456583
TI  - Fetal adrenal gland biometry and cervical elastography as predictors of preterm
      birth: A comparative study.
AB  - Background: Preterm birth is a major health problem in developing and developed
      countries leading to rising health care costs and long-term neurodevelopmental
      disability. The study aims to evaluate the role of new quantitative markers, like
      the elastography of cervix (shear wave speed estimation), fetal adrenal zone
      enlargement, and corrected fetal adrenal gland volume; in preterm birth
      prediction and analyze their relative importance. Thus, these markers may be
      beneficial in early preterm birth detection and prevent the related morbidities.
      Methods: Thirty pregnant females (from 28 to 37 weeks of gestational age),
      showing clinical signs and delivery outcome of preterm birth were included in the
      study with an equal number of not-in-labor antenatal females at >=37 weeks as
      controls. These patients were categorized as preterm and term groups. Both the
      groups were subjected to trans-abdominal ultrasonography where cervical length,
      cervical shear wave speed (dynamic elastography) and fetal adrenal gland
      parameters were measured. Results: Shear wave speed estimation of the antenatal
      cervix showed the highest sensitivity and specificity (96.7% and 87%
      respectively) in the prediction of preterm birth and also showed a strong
      correlation with fetal adrenal gland enlargement. Fetal adrenal zone enlargement
      was also shown to be a reliable marker of preterm birth, however, with reduced
      sensitivity and specificity than shear wave speed. Conclusion: The elastographic
      advancement and fetal adrenal biometry derived quantitative markers can be used
      as an objective and standard criterion for accurate prediction of preterm birth.

PMID- 29456586
TI  - Dietary canolol protects the heart against the deleterious effects induced by the
      association of rapeseed oil, vitamin E and coenzyme Q10 in the context of a high
      fat diet.
AB  - Background: Obesity progressively leads to cardiac failure. Omega-3
      polyunsaturated fatty acids (PUFA) have been shown to have cardio-protective
      effects in numerous pathological situations. It is not known whether rapeseed
      oil, which contains alpha-linolenic acid (ALA), has a similar protective effect.
      Omega-3 PUFAs are sensitive to attack by reactive oxygen species (ROS), and lipid
      peroxidation products could damage cardiac cells. We thus tested whether dietary
      refined rapeseed oil (RSO) associated with or without different antioxidants
      (vitamin E, coenzyme Q10 and canolol) is cardio-protective in a situation of
      abdominal obesity. Methods: Sixty male Wistar rats were subdivided into 5 groups.
      Each group was fed a specific diet for 11 weeks: a low-fat diet (3% of lipids, C
      diet) with compositionally-balanced PUFAs; a high-fat diet rich in palm oil (30%
      of lipids, PS diet); the PS diet in which 40% of lipids were replaced by RSO (R
      diet); the R diet supplemented with coenzyme Q10 (CoQ10) and vitamin E (RTC
      diet); and the RTC diet supplemented with canolol (RTCC diet). At the end of the
      diet period, the rats were sacrificed and the heart was collected and immediately
      frozen. Fatty acid composition of cardiac phospholipids was then determined.
      Several features of cardiac function (fibrosis, inflammation, oxidative stress,
      apoptosis, metabolism, mitochondrial biogenesis) were also estimated. Results:
      Abdominal obesity reduced cardiac oxidative stress and apoptosis rate by
      increasing the proportion of arachidonic acid (AA) in membrane phospholipids.
      Dietary RSO had the same effect, though it normalized the proportion of AA.
      Adding vitamin E and CoQ10 in the RSO-rich high fat diet had a deleterious
      effect, increasing fibrosis by increasing angiotensin-2 receptor-1b (Ag2R-1b)
      mRNA expression. Overexpression of these receptors triggers coronary
      vasoconstriction, which probably induced ischemia. Canolol supplementation
      counteracted this deleterious effect by reducing coronary vasoconstriction.
      Conclusion: Canolol was found to counteract the fibrotic effects of vitamin E +
      CoQ10 on cardiac fibrosis in the context of a high-fat diet enriched with RSO.
      This effect occurred through a restoration of cardiac Ag2R-1b mRNA expression and
      decreased ischemia.

PMID- 29456585
TI  - Neuroinflammation and neurohormesis in the pathogenesis of Alzheimer's disease
      and Alzheimer-linked pathologies: modulation by nutritional mushrooms.
AB  - Human life develops and expands not only in time and space, but also in the
      retrograde permanent recollection and interweaving of memories. Therefore,
      individual human identity depends fully on a proper access to the
      autobiographical memory. Such access is hindered or lost under pathological
      conditions such as Alzheimer's disease, including recently associated oxidant
      pathologies, such as ocular neural degeneration occurring in glaucoma or
      neurosensorial degeneration occurring in Meniere's disease. Oxidative stress and
      altered antioxidant systems have been suggested to play a role in the aetiology
      of major neurodegenerative disorders, and altered expression of genes sensing
      oxidative stress, as well as decreased cellular stress response mechanisms could
      synergistically contribute to the course of these oxidant disorders. Thus, the
      theory that low levels of stress can produce protective responses against the
      pathogenic processes is a frontier area of neurobiological research focal to
      understanding and developing therapeutic approaches to neurodegenerative
      disorders. Herein, we discuss cellular mechanisms underlying AD neuroinflammatory
      pathogenesis that are contributory to Alzheimer's disease. We describe endogenous
      cellular defence mechanism modulation and neurohormesis as a potentially
      innovative approach to therapeutics for AD and other neurodegenerative conditions
      that are associated with mitochondrial dysfunction and neuroinflammation.
      Particularly, we consider the emerging role of the inflammasome as an important
      component of the neuroprotective network, as well as the importance of Coriolus
      and Hericium nutritional mushrooms in redox stress responsive mechanisms and
      neuroprotection.

PMID- 29456587
TI  - Dietary diversity and associated factors among children of Orthodox Christian
      mothers/caregivers during the fasting season in Dejen District, North West
      Ethiopia.
AB  - Background: Proper feeding practices during early childhood is fundamental for
      optimal child growth and development. However, scientific evidences on the
      determinants of dietary diversity are scanty. Particularly, the impact of fasting
      on children's dietary diversity is not explored in Ethiopia. The aim of this
      study was to assess dietary diversity and associated factors among children aged
      6-23 months, whose mothers/care-givers were Orthodox Christians during the
      fasting season (Lent), in Dejen District, North West Ethiopia, 2016. Methods: A
      community based cross-sectional study was conducted during the fasting season
      from March to April, 2016. The study sample were children aged 6-23 months, whose
      mothers/care-givers were Orthodox Christians. A systematic random sampling
      technique was used to select a sample of 967 children proportionally from all
      selected kebeles. Data was entered using Epi data and statistical analysis were
      done using logistic regression. P-value < 0.05 at 95% confidence interval was
      taken as statistically significant. Results: Only 13.6% of children surveyed met
      the minimum requirement for dietary diversity. Unsatisfactory exposure to media
      [AOR = 5.22] and low household monthly income [AOR = 2.20] were negatively
      associated with dietary diversity. As compared to economic related reasons,
      mothers/caregivers who do not feed diet of animal origin to their children due to
      fear of utensil contamination for family food preparation were 1.5 times
      [AOR=1.5; 95% CI (1.05 - 2.53)] less likely to feed the recommended dietary
      diversity. Conclusions: The findings of this study revealed that the diet of
      children in the study area lacked diversity. Promoting mass media and
      socioeconomic empowerment of women have positive contribution to optimal child
      feeding practice. Sustained nutrition education to mothers regarding proper
      infant and young child feeding practice in collaboration with the respective
      religious leaders is highly recommended.

PMID- 29456588
TI  - A survey of caregiver burden in those providing informal care for patients with
      schizophrenia or bipolar disorder with agitation: results from a European study.
AB  - Background: Agitation is a common feature of bipolar disorder and schizophrenia.
      Previous research indicates that specific symptoms impact caregiver burden in
      these conditions, but the impact of agitation on caregiver experience is poorly
      understood. The aim of this study was to characterise caregiver burden in
      providers of informal care for patients with bipolar disorder and schizophrenia
      who experience agitation. Methods: In total, 297 matched patient and caregiver
      surveys were collected across the UK, Germany and Spain between October 2016 and
      January 2017. To be eligible, caregivers needed to provide informal care to a
      patient with a diagnosis of bipolar disorder or schizophrenia with agitation
      managed in a community setting and participating in the patient survey. The
      caregiver survey captured information on demographics and their role in managing
      the patient's agitation. Caregiver burden was assessed using the Involvement
      Evaluation Questionnaire. Descriptive analysis was conducted. Results: Caregivers
      provided 38.3 h (SD +/- 40.34) a week of support to the patient with 20%
      providing 50 h or more. Most caregivers reported that they recognised an episode
      of agitation all of the time (44%, n = 130) or sometimes (40%, n = 119). Verbal
      de-escalation techniques (talking (80%, n = 239) and soothing (73%, n = 218) were
      the most commonly reported strategies used by caregivers during an episode of
      agitation; 14% (n = 43) reported resorting to physically restraining the patient.
      Caregivers supervised rescue medication administration regularly (41%, n = 69) or
      occasionally (49%, n = 82). Mean Involvement Evaluation Questionnaire score was
      32.2 (+/- 15.27), equivalent to 28.4 (+/- 13.56) in Germany, 35.6 (+/- 16.55) in
      Spain and 33.3 (+/- 15.15) in the UK. Involvement Evaluation Questionnaire scores
      were higher for caregivers who reported hostile (41.7 +/- 17.07) lack of control
      (40.3 +/- 16.35) and violent (39.5 +/- 16.40) patient behaviours when agitated.
      Over excitement (31.8 +/- 15.05), restless (32.6 +/- 14.77) and tense (32.9 +/-
      15.64) behaviours were associated with a lower Involvement Evaluation
      Questionnaire score. Conclusions: Caregivers are active participants in the
      recognition and management of agitation episodes. The substantial burden reported
      by these caregivers is impacted by factors including the number of hours of care
      provided, patient behaviours and country. These may be viable targets for
      effective interventions to reduce caregiver burden.

PMID- 29456589
TI  - Employment status and changes in working career in relation to asthma: a cross
      sectional survey.
AB  - Background: Asthmatics confront inconveniences in working life that make it more
      difficult to pursue a sustainable career, such as unemployment and work
      disability. Ways of dealing with these inconveniences may be career changes. More
      needs to be known about the backgrounds and consequences of career changes among
      asthmatics, especially their relation to asthma or a change in asthma symptoms.
      The aim of this study was to compare earlier career changes of adults with asthma
      who are working full time to those who have drifted away from active working life
      because of work disability, unemployment or early retirement. The frequency of
      having changed tasks, work place or occupation, whether the changes had been
      driven by asthma and furthermore, whether the changes had affected their asthma
      symptoms were investigated. Methods: In this population-based survey study, all
      patients with reimbursement rights for asthma aged 20-65 years in the city of
      Tampere (total population 190,000), Finland (n = 2613) were recruited. The
      questionnaire was sent in October 2000 and the response rate was 79%. The
      questionnaire included questions e.g. on changing tasks, work place and
      occupation, whether these changes were driven by asthma or associated with change
      of asthma symptoms. The respondents were divided into four groups: working full
      time, work disability, unemployed and retired due to age. We applied ANOVA with
      Dunnet's post-test (variances were not equal between the groups) for a continued
      variable age and Chi-squared tests for categorical variables. Logistic regression
      models were built using unemployed vs. full-time work or work disability vs. full
      time work as an outcome variable. A p-value of <.05 was considered statistically
      significant. Results: Adults with asthma working full time had more often made
      changes in their career, but not as often driven by asthma as those with current
      work disability. The reason for changing work place compared to full-time workers
      (24.9%) was more often mainly or partly due to asthma among those with work
      disability (47.9%, p < 0.001) and the unemployed (43.3%, p = 0.006). Of those who
      made career changes because of asthma, a major proportion (over 67%) reported
      relief in asthma symptoms. Changing tasks (OR 5.8, 95% CI 1.9-18.0, for
      unemployment vs. full-time work), work place (OR 2.8, 95% CI 1.1-7.0, for work
      disability vs. full-time work and OR 2.6, 95% CI 1.3-5.4, for unemployment vs.
      full-time work) or occupation (OR 2.7, 95% CI 1.2-6.0, for unemployment vs. full
      time work) mainly because of asthma was associated with an elevated risk for
      undesirable employment status even after adjusting for age, gender, smoking and
      professional status. Conclusions: Career changes that were made mainly because of
      asthma were associated with undesirable employment status in this study. However,
      asthma symptoms were relieved after career changes especially among those who
      reported asthma to be the reason for the change. In addition to proper treatment
      and counselling of asthma patients towards applicable area of work or study, it
      may be beneficial to support early career changes in maintaining sustainable
      working careers among adults with asthma.

PMID- 29456591
TI  - Gender, money and professional identity: medical social work and the coming of
      the British National Health Service.
AB  - The arrival of the British National Health Service (NHS) in 1948 heralded
      significant changes for all health workers, but the establishment of a 'free'
      health service was especially meaningful for the hospital almoners-or medical
      social workers, as they were starting to be known-who had previously been
      responsible for the assessment and collection of patient payments. It was on this
      basis they had gained a foothold in the hospital, capitalising on gendered
      assumptions of financial understanding and behaviour. Yet what might have caused
      an identity crisis was embraced. This was a dual strategy of both repositioning
      the profession in alignment with the planned NHS and of asserting an enhanced
      professional status by distancing themselves from the handling of payment. It was
      an episode in the history of this distinctly female profession that speaks to
      women's historic relationship with money.

PMID- 29456590
TI  - Delayed initiation of breastfeeding in Bukavu, South Kivu, eastern Democratic
      Republic of the Congo: a cross-sectional study.
AB  - Background: Timely initiation of breastfeeding can decrease neonatal mortality.
      However, about 50% of newborns are not breastfeed within 1 h of birth in the
      Democratic Republic of Congo. The aim of this study was to identify factors
      associated with delayed initiation of breastfeeding in an urban and rural area of
      Bukavu, South Kivu province, Democratic Republic of Congo. Methods: We
      interviewed 396 mother-newborn pairs (185 in the urban area and 211 in the rural
      area) between 20 July and 10 October 2016. We used descriptive statistics to
      demonstrate the prevalence of early initiation of breastfeeding. Variables that
      showed association with delayed initiation of breastfeeding in the bivariate
      models were entered in a multivariable logistic model. Results: Overall, the rate
      of early initiation of breastfeeding was 65.9% (69.7% in the rural area, 61.6% in
      the rural area). Two hundred and seventy-four (62.9%) mothers (159 in rural area
      and 115 in urban area) were counselled on early initiation of breastfeeding
      during prenatal care. Most mothers, 65.2% received counselling by a health
      professional. On multivariable regression analyses after adjusting for other
      variables in the model, unmarried mothers [Odds Ratio (OR): 1.5 (95% Confidence
      Interval (CI): 1.13, 1.95)], cesarean delivery [OR: 2.24 (95% CI: 1.74, 2.88)],
      no counselling on timely initiation of breastfeeding [OR: 1.71 (95% CI: 1.29,
      2.20)] and counselling by a non-health professional [OR: 1.84 (95% CI: 1.08,
      3.12)] were associated with delayed initiation of breastfeeding. Conclusion:
      Systemic changes are needed for women having caesarean births to experience skin
      to-skin and early initiation. In addition, information, education and
      communication on the importance of timely initiation of breastfeeding must be
      supported to improve maternal and infant wellbeing.

PMID- 29456592
TI  - This month in JICS.

PMID- 29456593
TI  - Presumed evidence in deemed consent to organ donation.

PMID- 29456594
TI  - In defence of ward-based non-invasive ventilation.

PMID- 29456595
TI  - Geographical access to critical care services in Scotland.
AB  - Background: Critical illness requires specialist and timely management. The aim
      of this study was to create a geographic accessibility profile of the Scottish
      population to emergency departments and intensive care units. Methods: This was a
      descriptive, geographical analysis of population access to 'intermediate' and
      'definitive' critical care services in Scotland. Access was defined by the number
      of people able to reach services within 45 to 60 min, by road and by helicopter.
      Access was analysed by health board, rurality and as a country using freely
      available geographically referenced population data. Results: Ninety-six percent
      of the population reside within a 45-min drive of the nearest intermediate
      critical care facility, and 94% of the population live within a 45-min ambulance
      drive time to the nearest intensive care unit. By helicopter, these figures were
      95% and 91%, respectively. Some health boards had no access to definitive
      critical care services within 45 min via helicopter or road. Very remote small
      towns and very remote rural areas had poorer access than less remote and rural
      regions.

PMID- 29456596
TI  - Bridging the logistical gap between ultrasound enthusiasm and accreditation.
AB  - Point-of-care ultrasound is increasingly recognised as a valuable adjunct to
      patient care. Trainees in intensive care medicine are expected to accredit in
      focused intensive care echocardiography, but the availability of trained mentors
      and logistical/geographical factors make this difficult within the time
      constraints required. As a result, many trainees who are enthusiastic about point
      of-care ultrasound find it difficult to achieve accreditation. We present a
      secure, web-based, multi-user system which mitigates many of these difficulties
      and allows for clinical mentorship to take place without geographical barriers,
      and at a time convenient for the participants.

PMID- 29456597
TI  - Insertion rates and complications of central lines in the UK population: A pilot
      study.
AB  - Background: Central venous catheters are inserted ubiquitously in critical care
      and have roles in drug administration, fluid management and renal replacement
      therapy. They are also associated with numerous complications. The true number of
      central venous catheters inserted per year and the proportion of them associated
      with complications are unknown in the UK. Methods: We performed a prospective
      audit at five hospitals, as a feasibility pilot for a larger, nationwide audit.
      Using a novel secure online data collection platform, developed earlier and
      adapted for this project, all central venous catheters inserted for patients
      admitted to the Intensive Care Units were documented at five pilot sites across
      the UK. Results: A total of 117 data collection forms were submitted. Users found
      the electronic data collection system easy to use. All data fields were ready for
      analysis immediately after data input. Out of the 117 central venous catheters,
      17 were haemodialysis catheters and five pulmonary artery introducers.
      Experienced practitioners (at least three years' experience) inserted 85% of the
      central venous catheters. The site of insertion was the internal jugular vein for
      80%, femoral for 12% and subclavian for 8% of central venous catheters. Most
      central venous catheters were inserted in ICU (49%) or theatres (42%). Ultrasound
      was used for 109 (93%) of central venous catheter insertions and its use was not
      associated with fewer complications. In 15 cases venopuncture was attempted more
      than once (all with ultrasound) and this was associated with significantly
      increased risk of complications. There were eight immediate complications (6.8%):
      five related to venopuncture and inability to pass a guidewire, two carotid
      artery punctures and one associated with significant arrhythmia. Conclusion: This
      study demonstrates the ease and feasibility of collecting detailed descriptive
      data on central line insertion and its immediate complications in the UK over two
      weeks. In our proposed nationwide audit, organisation-level data on local
      policies and standard operating procedures is required to complete the picture on
      this important aspect of intensive care practice.

PMID- 29456598
TI  - 'It's learned on the job and it depends who you're with.' An observational
      qualitative study of how internal jugular cannulation is taught and learned.
AB  - Internal jugular cannulation may lead to serious complications. Ultrasound
      guidance is advocated; however, procedural complications remain a concern.
      Inconsistent education may be in part responsible for this. This study examined
      how internal jugular cannulation is taught and learned. An ethnographic approach
      was used in two acute hospitals. Methods comprised interviews, observations and
      focus groups. An inductive thematic analysis was undertaken. Three themes were
      identified: apprenticeship, trust and reciprocity. In apprenticeship, a new form
      of apprenticeship learning, necessitated by the structure of training is
      described. In trust the strategies by which trainers assess trainees' competence
      in order to allow them to gain experience is explored. In reciprocity the
      beneficial influence of trainees is illustrated. This study demonstrates how high
      stakes procedures are learned. It provides insights into under-investigated
      topics such as the use of 'permitted mistakes' to stimulate reflection and the
      role played by trainees in promoting good practice.

PMID- 29456599
TI  - Deprivation of liberty and intensive care: an update post Ferreira.
AB  - The right to liberty and security of the person is protected by Article 5 of the
      European Convention on Human Rights which has been incorporated into the Human
      Rights Act 1998. The 2014 Supreme Court judgment in the case commonly known as
      Cheshire West provided for an 'acid test' to be employed in establishing a
      deprivation of liberty. This 'acid test' of 'continuous supervision and not free
      to leave' led to concerns that patients lacking capacity being treated on an
      Intensive Care Unit could be at risk of a 'deprivation of liberty', if this
      authority was applicable to this setting. This article revisits the aftermath of
      Cheshire West before describing the recent legal developments around deprivation
      of liberty pertaining to intensive care by summarising the recent Ferreira
      judgments which appear for now to answer the question as to the applicability of
      Cheshire West in life-saving treatment.

PMID- 29456600
TI  - Conscientious objection to deceased organ donation by healthcare professionals.
AB  - In this article, we analyse the potential benefits and disadvantages of
      permitting healthcare professionals to invoke conscientious objection to deceased
      organ donation. There is some evidence that permitting doctors and nurses to
      register objections can ultimately lead to attitudinal change and acceptance of
      organ donation. However, while there may be grounds for conscientious objection
      in other cases such as abortion and euthanasia, the life-saving nature of
      donation and transplantation renders objection in this context more difficult to
      justify. In general, dialogue between healthcare professionals is a more
      appropriate solution, and any objections must be justified with a strong
      rationale in hospitals where such policies are put in place.

PMID- 29456601
TI  - The life and work of Jean-Martin Charcot (1825-1893): 'The Napoleon of Neuroses'.

PMID- 29456602
TI  - Review of management in cardiotoxic overdose and efficacy of delayed intralipid
      use.
AB  - We present the case of a 51-year-old woman admitted to our intensive care unit
      following an intentional overdose of a calcium channel antagonist and a beta
      blocker. The resultant hypotension was reversed with glucagon, noradrenaline,
      calcium and high-dose insulin. Despite these interventions, she remained
      vasoplegic and received a delayed, standard dose of intralipid. Subsequently, the
      vasoplegia resolved rapidly, and the vasopressor was stopped. Here, we review the
      management of overdose of calcium channel and beta-adrenergic receptor blockers,
      concentrating on the pharmacology of lipid emulsion therapy. There remain some
      unanswered questions about lipid emulsion therapy: treatment with lipid therapy
      is usually advocated as soon as possible; this case report suggests that it
      remains efficacious even if its administration were delayed.

PMID- 29456603
TI  - Successful management of 70% acetic acid ingestion on the intensive care unit: A
      case report.
AB  - Acetic acid is an organic acid available in concentrations from 2 to 80%. Whilst
      lower concentrations of 2-6% are more commonly used as the table top condiment,
      vinegar, much stronger solutions are regularly used in Eastern Europe as food
      preservatives and cleaning solutions. Oral ingestion of greater than 12% has been
      reported to cause haemolysis, renal failure, shock and death. Most reported cases
      of deliberate or accidental poisoning are from Russia and Eastern Europe in the
      1980s, with very little currently in western publications. We present the case of
      a female patient who attempted suicide by drinking 250 ml of 70% acetic acid. Her
      widespread gastrointestinal injuries were managed conservatively, and despite
      suffering extensive upper airway and renal complications, she was successfully
      decannulated and discharged home after a prolonged intensive care and hospital
      stay.

PMID- 29456604
TI  - Death from Kratom toxicity and the possible role of intralipid.
AB  - We present the case of a 26-year-old man who was brought into our emergency
      department in cardiorespiratory arrest, having taken Kratom 24 h previously.
      Despite multi-organ support, he deteriorated and died from cardiorespiratory
      failure and hypoxic brain damage 12 h later. Lipid emulsion was given, with
      significant temporary improvement in the cardiorespiratory failure. Kratom is
      derived from Mitragyna speciosa, a tropical deciduous and evergreen tree in the
      coffee family, and is native to Southeast Asia, and its leaves are used as a
      legal high in some parts of the world. Here, we review the pharmacochemistry of
      the drug, and wish to highlight that the effects of Kratom may not be as benign
      as are commonly reported, and the possible role of intralipid in managing the
      Kratom toxicity in this case.

PMID- 29456605
TI  - Bleeding during percutaneous dilatational tracheostomy - What to do while waiting
      for the surgeon?
AB  - A patient suffered significant bleeding during an attempt at percutaneous
      dilatational tracheostomy due to an aberrant anterior jugular vein. Bleeding was
      controlled with pressure temporarily, but quickly returned necessitating
      conversion to an open technique. We present an algorithm for the management of
      significant peri-procedural bleeding during this procedure.

PMID- 29456606
TI  - Sudden cardiac arrest in hypertrophic cardiomyopathy with dynamic cavity
      obstruction: The case for a decatecholaminisation strategy.
AB  - Catecholamines are entrenched in the management of shock states. A paradigm shift
      has pervaded the critical care arena in recent years acknowledging their
      propensity to cause harm and fuel a 'death-spiral'. We present the case of a 21
      year-old male following a witnessed out-of-hospital cardiac arrest who received
      high-quality cardiopulmonary resuscitation and standard advanced life support for
      refractory ventricular fibrillation until return of spontaneous circulation after
      70 min. Early post-admission echocardiography revealed severe diffuse sub-basal
      left ventricular hypertrophy with dynamic mid-cavity obstruction and akinetic
      apical pouching. Within this context, a decatecholaminised strategy comprising a
      beta-blocker was used to augment the left ventricular end-diastolic volume and
      attain cardiovascular stability.

PMID- 29456607
TI  - Temporising an extradural haematoma by intraosseous needle craniostomy in the
      District General Hospital by non-neurosurgical doctors - A case report.
AB  - We report the case of a 69-year-old man admitted to the emergency department of a
      UK district general hospital with an extradural haematoma following closed head
      injury. He deteriorated rapidly before transfer to the regional neurosurgical
      centre and was treated with decompression of the extradural haematoma through an
      EZ-IOTM intraosseous needle in our department, with telephone guidance from the
      neurosurgeon. We believe this to be the first reported use of this technique in a
      district general hospital.

PMID- 29456608
TI  - Outcomes following the use of nebulized heparin for inhalation injury (HIHI
      Study).

PMID- 29456609
TI  - Trache teams.

PMID- 29456610
TI  - How can we improve adoption of protective mechanical ventilation in United
      Kingdom critical care units?

PMID- 29456611
TI  - Intra-operative mechanical ventilation strategies in cardiac surgical patients.

PMID- 29456613
TI  - Lemmingaid.

PMID- 29456612
TI  - The safety of regional citrate anticoagulation in renal replacement therapy.

PMID- 29456615
TI  - How has the presidential election affected young Americans?
AB  - The 2016 presidential election season and subsequent political events have had
      physical and emotional impacts on youth. We collected qualitative insights from
      14 to 24 year olds across the US related to these events over time. Open-ended
      probes were sent via text message at three time points before and after the 2016
      presidential election. The majority of youth reported emotional stress during all
      three time points, and female participants were significantly more likely to
      experience emotional responses. White participants were more likely to report
      negative symptoms than their peers both pre-election and at 4-months post
      election. While preliminary, the results indicate that feelings of stress,
      anxiety, and fear have persisted in the months following the election,
      particularly for young women. Additional research is needed to examine the long
      term effects of political events on the emotional and physical health of youth.

PMID- 29456616
TI  - The mortality-incidence ratio as an indicator of five-year cancer survival in
      metropolitan Lima.
AB  - Introduction: The Mortality-Incidence Ratio complement [1 - MIR] is an indicator
      validated in various populations to estimate five-year cancer survival, but its
      validity remains unreported in Peru. This study aims to determine if the MIR
      correlates directly with five-year survival in patients diagnosed with the ten
      most common types of cancer in metropolitan Lima. Materials and methods: The
      Metropolitan Lima Cancer Registry (RCLM in Spanish) for 2004-2005 was used to
      determine the number of new cases and the number of deaths of the following
      cancers: breast, stomach, prostate, thyroid, lung, colon, cervical, and liver
      cancers, as well as non-Hodgkin's lymphoma and leukaemia. To determine the five
      year survival, the five-year vital status of cases recorded was verified in the
      National Registry of Identification and Civil Status (RENIEC in Spanish). A
      linear regression model was used to assess the correlation between [1 - MIR] and
      total observed five-year survival for the selected cancers. Results: Observed and
      estimated five-year survival determined by [1 - MIR] for each neoplasia were
      thyroid (66.7%, 86.7%), breast (69.6%; 68%), prostate (64.3%, 63.8%) and cervical
      (50.1%, 58.5%), respectively. Pearson's r coefficient for the correlation between
      [MIR - 1] and observed survival was = 0.9839. Using the coefficient of
      determination, it was found that [1 - MIR] (X) captures the 96.82% of observed
      survival (Y). Conclusion: The Mortality-Incidence Ratio complement [1 - MIR] is
      an appropriate tool for approximating observed five-year survival for the ten
      types of cancers studied. This study demonstrates the validity of this model for
      predicting five-year survival in cancer patients in metropolitan Lima.

PMID- 29456617
TI  - Solitary breast neurofibroma: imaging aspects.
AB  - Neurofibromas are benign peripheral nerve sheath tumours, which are usually
      solitary and sporadic. Solitary neurofibromas of the breast are rare. The most
      common location of a breast neurofibroma is the nipple-areola complex. We report
      a rare case of a 56-year-old woman with a solitary neurofibroma of the right
      breast sulcus.

PMID- 29456618
TI  - An unusual presentation of adult T-cell leukemia/lymphoma.
AB  - Adult T-cell Leukemia/Lymphoma (ATL) is a rare disease, related to human T
      lymphotropic virus-1 (HTLV-1) and presented mainly in adulthood by generalised
      lymphadenopathy, hepatosplenomegaly, skin lesions and hypercalcaemia, with rare
      gastrointestinal and/or oral manifestations. We reported this case to raise
      awareness and demonstrate the therapeutic challenges of this rare disease. A 49
      year-old Japanese female presented with skin papules on both forearms, painful
      mouth ulcers and multiple neck swellings since early February 2017. Initial
      clinical examination and laboratory investigations were misleading and her
      condition was diagnosed as candidiasis. Because of un-improvement of the case, a
      screening upper endoscopy was requested 2 months later and revealed
      characteristic oropharyngeal ulcers which were biopsied, and its pathologic
      examination confirmed smouldering type ATL. This case report should raise
      awareness of doctors and endoscopists about this disease especially in HTLV-1
      endemic areas to avoid late diagnosis and help achieve earlier therapeutic
      decisions.

PMID- 29456619
TI  - A systematic review of the literature exploring the interplay between prostate
      cancer and type two diabetes mellitus.
AB  - Prostate cancer (PCa) and type two diabetes mellitus (T2DM) are both increasing
      prevalent conditions and often occur concurrently. However, the relationship
      between the two is more complex than just two prevalent conditions co-existing.
      This review systematically explores the literature around the interplay between
      the two conditions. It covers the impact of pre-existing T2DM on PCa incidence,
      grade and stage, as well as exploring the impact of T2DM on PCa outcomes and
      mortality and the interaction between T2DM and PCa treatments.

PMID- 29456621
TI  - Men seeking counselling in a Breast Cancer Risk Evaluation Clinic.
AB  - Background: Hereditary breast and ovary cancer syndrome affects both genders but
      little is known about the uptake of genetic services by men. The objective of
      this study is to characterise the male population counselled through a
      multidisciplinary breast/ovarian program. Methods: Descriptive analysis of male
      patients counselled from January 2000 to December 2015. Data in this analysis
      include new cancer diagnoses during prospective follow up. Results: From 4,320
      families registered, 362 male patients were identified: 236 (65.2%) from
      hereditary cancer families (HCF) and 126 (34.8%) from non-HCF. In HCF, 121
      patients (51.3%) were mutation carriers (MC): BRCA2 - 102 (84.3%), BRCA1 - 16
      (13.2%), CHEK2 - 1 (0.8%) and TP53 - 2 (1.7%). Non-HCF included 126 patients: 85
      (67.5%) belonged to families without pathogenic mutations or with variants of
      unknown clinical significance; 22 (17.5%) refused testing after counselling and
      19 (15.0%) did not meet criteria for testing. Both HCF and non-HCF included
      patients with previous cancer diagnoses: HCF- Breast Cancer (BC) - 18; prostate
      cancer (PC) - 13; melanoma - 1; others - 7) and non-HCF (BC - 77; PC - 20;
      gastric cancer (GC) - 1; melanoma - 8; bladder cancer - 1; others - 22). From the
      121 MC identified (including the TP53 and CHEK2 carriers), 97 patients (80.2%)
      adhered to prospective surveillance. With a median follow-up of 36.9 months, 17
      cancers were diagnosed in 14 patients, PC being the most frequently diagnosed
      neoplasia (5 cases). Eleven patients (78.6%) are alive and three patients died of
      advanced cancer (2 with GC, 1 with disseminated adenocarcinoma). Conclusion: We
      observed a high adherence to counselling, genetic testing and active surveillance
      by men belonging to hereditary BC families. Male carriers of pathogenic DNA
      variants are at risk for several cancers and should be included in prospective
      follow-up studies.

PMID- 29456622
TI  - Does the oncology community have a rejection bias when it comes to repurposed
      drugs?
AB  - Among the various measures proposed to combat the challenge of financial toxicity
      in cancer care, an important strategy is the use of lower-priced drugs instead of
      expensive alternatives. However, the oncology community seems to either ignore or
      more readily reject cheaper drugs in cancer care compared to more expensive
      alternatives. In this commentary, we present three examples of lower-priced drugs
      rejected or ignored by the oncology community and contrast this with three
      expensive drugs where persistent optimism remained despite negative clinical
      trial results. We argue that all drugs be held to the same rigorous standards -
      this not only includes skepticism in the absence of sound evidence, but also the
      suspension of premature judgement as has happened in the cases of repurposed
      drugs.

PMID- 29456620
TI  - Endometriosis and endometriosis-associated cancers: new insights into the
      molecular mechanisms of ovarian cancer development.
AB  - Endometriosis is a fascinating disease that we strive to better understand.
      Molecular techniques are shedding new light on many important aspects of this
      disease: from pathogenesis to the recognition of distinct disease variants like
      deep infiltrating endometriosis. The observation that endometriosis is a cancer
      precursor has now been strengthened with the knowledge that mutations that are
      present in endometriosis-associated cancers can be found in adjacent
      endometriosis lesions. Recent genomic studies, placed in context, suggest that
      deep infiltrating endometriosis may represent a benign neoplasm that invades
      locally but rarely metastasises. Further research will help elucidate distinct
      aberrations which result in this phenotype. With respect to identifying those
      patients who may be at risk of developing endometriosis-associated cancers, a
      combination of molecular, pathological, and inheritance markers may define a high
      risk group that might benefit from risk-reducing strategies.

PMID- 29456623
TI  - Osteonecrosis of the jaw (ONJ) in patients who receive Bone Targeting Agents
      (BTAs): the power of e-learning.
AB  - The definition, pathobiology and risk factors of ONJ in cancer patients who
      receive BTAs are discussed in the recent ecancer module for osteonecrosis of the
      jaw (http://ecancer.org/education/module/276-osteonecrosis-of-the-jaw.php). ONJ
      prevention, early diagnosis and management are presented. The critical question
      of the performance of dental extraction, during BTA therapy, as indicated with
      the recent studies, is supported. The importance of the collaboration between
      dental and oncology professionals and the patients is highlighted and can be
      achieved through appropriate education. The ecancer modules are valuable tools
      for successful e-learning in medical oncology education, including ONJ.

PMID- 29456624
TI  - The case for a regional approach to publication impact.
AB  - Healthcare-related research is largely regional. Put simply, this is because
      disease burdens differ between world regions. Even global burdens, such as
      ischaemic heart disease and cancer, display distinctive characteristics in
      certain regions that are not seen in others. Regional differences in
      infrastructure, resources and human capital further compound the differences
      seen, as they affect the way in which the local scientific community can interact
      with the local disease burden. As such, it seems fair to assume that healthcare
      related research ought to be regionally distributed. Although translation of
      research between regions can sometimes be done, the larger the gap in
      infrastructure, resources or human capital between regions, the less likely it is
      that it can be adequately bridged. A recent example of this pertains to accepted
      life-saving treatment for sepsis in high-income settings, which had the opposite
      effect when implemented and evaluated in low-income Zambia. This regionality of
      clinical medicine is, however, not reflected in academic publishing; the impact
      of a journal is measured and understood by metrics that use the world as their
      denominator. Therefore, top medical journals are perceived to be relevant equally
      to all contexts and regions. However, there is a strong case to be made that this
      lack of granularity is deleterious, and that the creation of a regional impact
      metric would place clinicians, researchers, and libraries in a better position to
      understand which journals are relevant to their context and practice.

PMID- 29456626
TI  - Molybdenum anode: a novel electrode for enhanced power generation in microbial
      fuel cells, identified via extensive screening of metal electrodes.
AB  - Background: Metals are considered a suitable anode material for microbial fuel
      cells (MFCs) because of their high electrical conductivity. However, only a few
      types of metals have been used as anodes, and an extensive screening of metals
      has not yet been conducted. In this study, to develop a new metal anode for
      increased electricity generation in MFCs, 14 different metals (Al, Ti, Fe, Ni,
      Cu, Zn, Zr, Nb, Mo, Ag, In, Sn, Ta, and W) and 31 of their oxidized forms were
      comprehensively tested. Oxidized-metal anodes were prepared using flame
      oxidation, heat treatment, and electrochemical oxidation. The selected anodes
      were further evaluated in detail using air-cathode single-chambered MFCs.
      Results: The untreated Mo and electrochemically oxidized Mo anodes showed high
      averages of maximum power densities in the screening test, followed by flame
      oxidized (FO) W, FO-Fe, FO-Mo, and Sn-based anodes. The untreated Mo and FO-W
      anodes were selected for further evaluation. X-ray analyses revealed that the
      surface of the Mo anode was naturally oxidized in the presence of air, forming a
      layer of MoO3, a known oxidation catalyst. A high maximum power density (1296
      mW/m2) was achieved using the Mo anode in the MFCs, which was superior to that
      obtained using the FO-W anode (1036 mW/m2). The Mo anode, but not the FO-W anode,
      continued to produce current without detectable corrosion until the end of
      operation (350 days). Geobacter was abundant in both biofilms on the Mo and FO-W
      anodes, as analyzed by high-throughput sequencing of the 16S rRNA gene.
      Conclusions: The screening test revealed that Mo, W, Fe, and Sn are useful MFC
      anode materials. The detailed analyses demonstrated that the Mo anode is a high
      performance electrode with structural simplicity and long-term stability in MFCs.
      The anode can be easily prepared by merely shaping Mo materials to the desired
      forms. These properties would enable the large-scale preparation of the anode,
      required for practical MFC applications. This study also implies the potential
      involvement of Geobacter in the Mo and W cycles on Earth.

PMID- 29456625
TI  - Alignment of microbial fitness with engineered product formation: obligatory
      coupling between acetate production and photoautotrophic growth.
AB  - Background: Microbial bioengineering has the potential to become a key
      contributor to the future development of human society by providing sustainable,
      novel, and cost-effective production pipelines. However, the sustained
      productivity of genetically engineered strains is often a challenge, as
      spontaneous non-producing mutants tend to grow faster and take over the
      population. Novel strategies to prevent this issue of strain instability are
      urgently needed. Results: In this study, we propose a novel strategy applicable
      to all microbial production systems for which a genome-scale metabolic model is
      available that aligns the production of native metabolites to the formation of
      biomass. Based on well-established constraint-based analysis techniques such as
      OptKnock and FVA, we developed an in silico pipeline-FRUITS-that specifically
      'Finds Reactions Usable in Tapping Side-products'. It analyses a metabolic
      network to identify compounds produced in anabolism that are suitable to be
      coupled to growth by deletion of their re-utilization pathway(s), and computes
      their respective biomass and product formation rates. When applied to
      Synechocystis sp. PCC6803, a model cyanobacterium explored for sustainable
      bioproduction, a total of nine target metabolites were identified. We tested our
      approach for one of these compounds, acetate, which is used in a wide range of
      industrial applications. The model-guided engineered strain shows an obligatory
      coupling between acetate production and photoautotrophic growth as predicted.
      Furthermore, the stability of acetate productivity in this strain was confirmed
      by performing prolonged turbidostat cultivations. Conclusions: This work
      demonstrates a novel approach to stabilize the production of target compounds in
      cyanobacteria that culminated in the first report of a photoautotrophic growth
      coupled cell factory. The method developed is generic and can easily be extended
      to any other modeled microbial production system.

PMID- 29456627
TI  - Growth and lipid accumulation by different nutrients in the microalga
      Chlamydomonas reinhardtii.
AB  - Background: Individual nutrient depletion is widely used to induce lipid
      accumulation in microalgae, which also causes cell growth inhibition and
      decreases the total biomass. Thus, improving the lipid accumulation without
      biomass loss in the nutrient deficiency cells becomes a potential cost-effective
      treatment for cheaper biofuels. Methods: In this study, the effects of different
      nutritional conditions on the growth and contents of lipids in Chlamydomonas
      reinhardtii were compared, and the metabolic profiles under different nutritional
      conditions were also investigated. Results: We showed that similar to other
      microalgae, nitrogen or phosphorus deficiency inhibited the growth of
      Chlamydomonas and combined nutrition deficiency reduced biomass by up to 31.7%,
      though lipid contents in cells (g/g dry weight [DW]) were significantly
      increased. The addition of sodium acetate countered this growth inhibition that
      resulted from nitrogen and phosphorus deficiency, with significantly increased
      biomass. Furthermore, the combination of 4 g/L sodium acetate supplementation
      with nitrogen and phosphorous deficiency increased total fatty acid yield (mg/L)
      by 93.0 and 150.1% compared to nutrient-depleted and normal culture conditions,
      respectively. Metabolite content was affected by the different nutritional
      conditions, especially metabolites that are involved in lipid metabolism, amino
      acid metabolism and metabolism of external substances. Conclusion: Further
      research into these metabolites could shed light onto the relationship between
      cell growth inhibition and fatty acid accumulation in Chlamydomonas.

PMID- 29456628
TI  - Identification of influential observations in high-dimensional cancer survival
      data through the rank product test.
AB  - Background: Survival analysis is a statistical technique widely used in many
      fields of science, in particular in the medical area, and which studies the time
      until an event of interest occurs. Outlier detection in this context has gained
      great importance due to the fact that the identification of long or short-term
      survivors may lead to the detection of new prognostic factors. However, the
      results obtained using different outlier detection methods and residuals are
      seldom the same and are strongly dependent of the specific Cox proportional
      hazards model selected. In particular, when the inherent data have a high number
      of covariates, dimensionality reduction becomes a key challenge, usually
      addressed through regularized optimization, e.g. using Lasso, Ridge or Elastic
      Net regression. In the case of transcriptomics studies, this is an ubiquitous
      problem, since each observation has a very high number of associated covariates
      (genes). Results: In order to solve this issue, we propose to use the Rank
      Product test, a non-parametric technique, as a method to identify discrepant
      observations independently of the selection method and deviance considered. An
      example based on the The Cancer Genome Atlas (TCGA) ovarian cancer dataset is
      presented, where the covariates are patients' gene expressions. Three sub-models
      were considered, and, for each one, different outliers were obtained.
      Additionally, a resampling strategy was conducted to demonstrate the methods'
      consistency and robustness. The Rank Product worked as a consensus method to
      identify observations that can be influential under survival models, thus
      potential outliers in the high-dimensional space. Conclusions: The proposed
      technique allows us to combine the different results obtained by each sub-model
      and find which observations are systematically ranked as putative outliers to be
      explored further from a clinical point of view.

PMID- 29456629
TI  - Acute vitamin C improves cardiac function, not exercise capacity, in adults with
      type 2 diabetes.
AB  - Background: People with type 2 diabetes (T2D) have impaired exercise capacity,
      even in the absence of complications, which is predictive of their increased
      cardiovascular mortality. Cardiovascular dysfunction is one potential cause of
      this exercise defect. Acute infusion of vitamin C has been separately shown to
      improve diastolic and endothelial function in prior studies. We hypothesized that
      acute vitamin C infusion would improve exercise capacity and that these
      improvements would be associated with improved cardiovascular function. Methods:
      Adults with T2D (n = 31, 7 female, 24 male, body mass index (BMI): 31.5 +/- 0.8
      kg/m2) and BMI-similar healthy adults (n = 21, 11 female, 10 male, BMI: 30.4 +/-
      0.7 kg/m2) completed two randomly ordered visits: IV infusion of vitamin C (7.5
      g) and a volume-matched saline infusion. During each visit peak oxygen uptake
      (VO2peak), brachial artery flow mediated dilation (FMD), reactive hyperemia (RH;
      plethysmography), and cardiac echocardiography were measured. General linear
      mixed models were utilized to assess the differences in all study variables.
      Results: Acute vitamin C infusion improved diastolic function, assessed by
      lateral and septal E:E' (P < 0.01), but did not change RH (P = 0.92), or VO2peak
      (P = 0.33) in any participants. Conclusion: Acute vitamin C infusion improved
      diastolic function but did not change FMD, forearm reactive hyperemia, or peak
      exercise capacity. Future studies should further clarify the role of endothelial
      function as well as other possible physiological causes of exercise impairment in
      order to provide potential therapeutic targets.Trial registration NCT00786019.
      Prospectively registered May 2008.

PMID- 29456631
TI  - A model of anterior cruciate ligament injury in cynomolgus monkeys developed via
      arthroscopic surgery.
AB  - The anterior cruciate ligament (ACL) is an important structure that maintains the
      stability of knee joints. Animal models of ACL injury are helpful to explore its
      underlying mechanisms, and strategies for prevention, treatment and
      rehabilitation. Therefore, the aim of the present study was to develop an
      efficient model of ACL injury in cynomolgus monkeys via arthroscopic techniques.
      In the present study, 18 cynomolgus monkeys were randomly divided into a model
      group (n=6), a sham operation group (n=6) and a blank control group (n=6). One
      quarter of the ACL was removed under arthroscopy in the model group. In the sham
      operation group, only arthroscopic exploration was performed as a control. In the
      blank control group, monkeys were housed under the same conditions for the same
      length of time. Magnetic resonance imaging examination was performed pre- and
      post-operatively, as well as measurements of the circumference of the thigh and
      calf, and of the maximum flexion degree of the knee. Anterior drawer test,
      Lachman test and pivot-shift tests were also performed. The results revealed that
      the injured side of the knees in the model group became unstable, as determined
      from evaluation of the physical tests. In conclusion, based on these findings,
      the modeling method of ACL injury was effective, and may contribute to the
      associated research concerning ACL injury.

PMID- 29456632
TI  - Arrhythmogenic cardiomyopathy: Identification of desmosomal gene variations and
      desmosomal protein expression in variation carriers.
AB  - Arrhythmogenic cardiomyopathy (AC) is an inherited disorder that is predominantly
      present in the right ventricular myocardium. Mutations in the genes encoding the
      desmosomal protein are thought to underlie the pathogenesis of AC. Since AC is
      genetically heterogeneous and phenotypically diverse, modifier genes and
      environmental factors have an important role in disease expression. The aim of
      the present study was to identify AC-associated desmosomal gene variations, and
      examine the expression levels of intercalated disc proteins in AC patients who
      carry the variations (DSG2 p.Leu797Gln, PKP2 p.Ser249Thr and p.E808fsX30). The
      results of the present investigation provided information on the search for
      modifier genes and desmosomal gene mutations, and improved our understanding of
      the mechanism underlying these AC mutations. Genetic screening of five desmosomal
      genes (DSG2, DSC2, JUP, PKP2, and DSP) in 23 patients with AC who underwent heart
      transplantation was performed and the expression levels and localizations of
      intercalated disc proteins were assessed using western blotting and
      immunohistochemistry, respectively. The results enabled the identification of
      three desmosomal gene variations (DSG2 L797Q, PKP2 S249T, and E808fsX30), two of
      which are reported for the first time. DSG2 L797Q was identified in one patient.
      The protein expression levels of DSG2 in the L797Q carrier were unchanged
      compared with the healthy controls, and the expression levels of the other
      proteins (JUP and Cx43) in the intercalated disc were also similar between the
      healthy controls, the variation carrier and the case controls. Two variations
      (S249T and E808fsX30) in PKP2 were identified in one patient, the protein
      expression levels of PKP2 in this patient were significantly decreased, and the
      expression levels of the other proteins in the intercalated disc was also
      decreased. The data suggest that there may be modifier genes and other AC
      associated mutations requiring identification, in order to further our
      understanding of the disease mechanism induced by these mutations.

PMID- 29456630
TI  - Roles of Eph/ephrin bidirectional signaling in central nervous system injury and
      recovery.
AB  - Multiple cellular components are involved in the complex pathological process
      following central nervous system (CNS) injury, including neurons, glial cells and
      endothelial cells. Previous studies and neurotherapeutic clinical trials have
      assessed the molecular mechanisms that underlie neuronal cell death following CNS
      injury. However, this approach has largely failed to reduce CNS damage or improve
      the functional recovery of patients. Erythropoietin-producing human
      hepatocellular (Eph) receptors and ephrin ligands have attracted considerable
      attention since their discovery, due to their extensive distribution and unique
      bidirectional signaling between astrocytes and neurons. Previous studies have
      investigated the roles of Eph/ephrin bidirectional signaling in the developing
      central nervous system. It was determined that Eph/ephrin bidirectional signaling
      is expressed in various CNS regions and cell types, and that it serves diverse
      roles in the adult CNS. In the present review, the roles of Eph/ephrin
      bidirectional signaling in CNS injuries are assessed.

PMID- 29456633
TI  - Crosstalk between apoptosis and autophagy in prostate epithelial cells under
      androgen deprivation.
AB  - The present study investigated the molecular mechanism of apoptosis and autophagy
      in prostate epithelial cells under androgen deprivation (AD). BPH-1 cells were
      divided into four groups as follows: Control (Cont), AD, autophagy inhibition
      (AI) and AD + AI groups. Cells in the four groups were treated accordingly, and
      the level of apoptosis was subsequently measured via flow cytometry. The
      expression of the microtubule-associated proteins 1A/1B light chain 3 (LC3),
      caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1) and Beclin-1 proteins of BPH-1
      cells was detected at different time points following culture in androgen
      deprived medium. Western blotting revealed that the basal levels of the LC3-II
      protein were detected at 0 h. At 4 h, LC3-II was significantly increased compared
      with 0 h (P<0.05). Beginning at 20 h, the expression level of the LC3-II protein
      decreased significantly (P<0.05). Western blotting revealed that beginning at 24
      h, the expression level of the PARP-1 protein decreased significantly (P<0.001)
      and the cleavage fragments of the PARP-1 protein appeared. These results further
      imply that autophagy serves a cell protective function by mutual inhibition with
      apoptosis in BPH-1 cells in the removal of androgen conditions. Furthermore, the
      fragments of the cleaved Beclin-1 protein appeared as 35 and 37 kDa bands. Flow
      cytometry analysis demonstrated that the rate of cell apoptosis in the AD, AI and
      AD + AI groups was significantly increased compared with the Cont group (P<0.01).
      Compared with the AD or the AI groups individually, the rate of cell apoptosis in
      the AD + AI group was significantly increased (P<0.001). These findings suggest
      that in the early stage of AD, autophagy has a compensatory function in the cell,
      whereas in the whole process, autophagy and apoptosis share a mutual antagonism.
      The Beclin-1-C protein fragment contributed positive feedback to the process of
      apoptosis, which may be a potential mechanism of AD therapy. Therefore, AD and AI
      exhibit a synergistic effect to further improve the level of apoptosis.

PMID- 29456634
TI  - Limethason reduces airway inflammation in a murine model of ovalbumin-induced
      chronic asthma without causing side effects.
AB  - Airway inflammation is the major pathological feature of asthma. Thus, the
      current therapeutic strategy for asthma is to control inflammation. Limethason,
      an anti-inflammation drug, is widely used in rheumatoid arthritis treatment. The
      aim of the present study was to detect the anti-inflammatory effect and side
      effects of limethason on airways that were sensitized with ovalbumin in a murine
      model of chronic asthma. In the present study, BALB/c mice were sensitized with
      ovalbumin. Airway hyperresponsiveness was estimated, and hematoxylin and eosin
      staining, Periodic acid-Schiff staining and bronchoalveolar lavage were used to
      detect the effect on chronic asthma. Limethason effectively reduced airway
      hyperresponsiveness, and inhibited inflammatory cell infiltration and mucus
      secretion. Bronchoalveolar lavage fluid analysis revealed that limethason
      suppressed levels of airway eosinophils. In the period of treatment, limethason
      exhibited no influence on morphology of the femoral head, bone mineral content or
      bone mineral density, which were detected by histological studies and dual-energy
      X-ray absorptiometry. The index of liver, spleen, kidney, gastrocnemius and brown
      adipose tissue also demonstrated that limethason had no adverse effects on organs
      and tissues. The present study revealed that limethason could effectively reduce
      inflammation in an asthma mouse model without side effects. Therefore, limethason
      may have therapeutic potential for treating chronic asthma clinically.

PMID- 29456635
TI  - Clinical effect of platelet-rich fibrin on the preservation of the alveolar ridge
      following tooth extraction.
AB  - The aim of the present study was to evaluate the clinical efficacy of platelet
      rich fibrin (PRF) in preserving the alveolar ridge following human tooth
      extraction. A total of 28 patients were divided into two groups: The experimental
      and control groups (n=14 each). Following tooth extraction, the experimental
      group was implanted with PRF membrane, whereas the control group was not. The
      gingival healing effect was assessed at 7 days, 1 and 3 months later. Cone-beam
      computed tomography was performed immediately and at 3 months following tooth
      extraction. The changes in alveolar ridge height, width, and bone mineral density
      were compared between the two groups. The alveolar bone was removed using the
      ring drill during the implant surgery at 3 months following tooth extraction.
      Histomorphometric evaluation was performed to compare new bone formation between
      groups. The patients in the experimental group reportedly felt better compared
      with the patients in the control group. The healing of gingival tissue was better
      in the experimental group than in the control group. A significantly greater
      novel bone area was observed in the PRF group compared with the control group
      (P<0.01). However, no statistically significant differences were observed in the
      mean value of buccal alveolar ridge height, lingual/palatal alveolar ridge height
      and alveolar ridge width between the two groups. These results suggested that PRF
      was advantageous in human alveolar ridge preservation with ease of use and simple
      handling. Histological analysis of novel bone formation confirmed that PRF
      increased the quality of the novel bone and enhanced the rate of bone formation,
      despite the effect of PRF was not significant to reduce alveolar bone resorption
      in the extraction socket alone.

PMID- 29456636
TI  - Expression of diaphragmatic myostatin and correlation with apoptosis in rats with
      chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by progressive
      airflow limitation and loss of lung function. The present study aimed to
      investigate the diaphragmatic protein expression of myostatin and its correlation
      with apoptosis in a rat model of CPOD. Sprague Dawley rats were randomly divided
      into a control group and a COPD group, the latter of which were exposed to
      cigarette smoke to build a rat model of COPD. The validity of the COPD model was
      evaluated by assessment of lung function and histopathological analysis.
      Diaphragmatic myostatin expression and apoptosis were measured by western blot
      and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end
      labeling, respectively. The rat model of COPD was efficiently established by
      cigarette smoke exposure. Diaphragmatic myostatin expression and apoptotic index
      in COPD rats were obviously increased as compared with that in the control
      animals. A positive correlation between diaphragmatic myostatin expression and
      apoptotic index was identified (r=0.857). Diaphragmatic myostatin overexpression
      in rats with COPD may promote diaphragmatic apoptosis and atrophy, leading to
      diaphragm weakness and respiratory muscle dysfunction, which is involved in the
      pathology of COPD.

PMID- 29456637
TI  - Effects of astrogaloside on the inflammation and immunity of renal failure
      patients receiving maintenance dialysis.
AB  - Chronic renal failure is a type of clinical syndrome originating from chronic
      renal diseases. The aim of the study was to investigate the effect of
      astrogaloside on the inflammation and immunity of renal failure patients
      receiving maintenance dialysis. We randomly selected 92 renal failure patients
      receiving maintenance dialysis who were admitted to hospital for treatment
      between May, 2015 and April, 2016. Patients were randomly divided into the
      control (n=46) and observation (n=46) groups. Patients in the control group
      received the regular dialysis plus the basic treatment in Western medicine, while
      in the observation group, patients additionally received astrogaloside via
      intravenous injection as treatment. We compared the clinical efficacy of patients
      between the two groups, residual renal function (RRF), changes in urine volume,
      variations in inflammatory indicators [C-reaction protein (CRP), interleukin-6
      (IL-6), IL-17, and tumor necrosis factor-alpha (TNF-alpha)] before and after
      treatment, and the levels of the thymus-dependent lymphocyte (T cells) subgroup
      (CD3+, CD4+, CD8+ and CD4+/CD8+) in the immune system of patients after
      treatment. In the observation group, the total effective rate was significantly
      higher than that in the control group (P<0.05). After 6 months, RRF and the urine
      volume of patients in the two groups were decreased when compared with the levels
      before treatment, and the decreasing rates of RRF and urine volume in the
      observation group were significantly lower than those in the control group
      (P<0.05). After treatment, the levels of human serum C reaction protein (hs-CRP),
      IL-6, IL-17 and TNF-alpha in the two groups were lower than those before
      treatment, and the decrease in the observation group was more significant than
      that in the control group (P<0.05). Following treatment, the levels of CD3+, CD4+
      and CD4+/CD8+ in the observation group were higher than those in the control
      group, and the level of CD8+ was lower than that in the control group (P<0.05).
      In conclusion, astrogaloside can delay the decrease in RRF of renal failure
      patients receiving the maintenance dialysis, ameliorate the inflammatory
      responses, and enhance the immune function, thereby increasing the disease
      resistance of patients and improving the clinical symptoms.

PMID- 29456638
TI  - Biobran/MGN-3, an arabinoxylan rice bran, enhances NK cell activity in geriatric
      subjects: A randomized, double-blind, placebo-controlled clinical trial.
AB  - Aging is associated with a decline in natural killer (NK) and natural killer T
      (NKT) cell function that may contribute to increased susceptibility to malignancy
      and infection. A preliminary investigation was conducted examining the hypothesis
      that arabinoxylan rice bran (Biobran/MGN-3), a denatured hemicellulose with known
      immunomodulatory activity, could counteract this decline in NK/NKT cell activity
      in geriatrics. A total of 12 healthy geriatric subjects of both sexes and over 56
      years old, participated in a randomized, double-blind, placebo-controlled
      clinical trial. A total of six subjects served as control and six subjects
      ingested Biobran/MGN-3 (500 mg/day) for 30 days. The effect of Biobran/MGN-3
      supplementation on NK/NKT cell activity was assessed using the degranulation
      assay. All study subjects were monitored for the development of any inadvertent
      side effects. In addition, the pharmacological effects of Biobran/MGN-3 on blood
      cell components and liver and kidney functions were also assessed. Results
      demonstrated that Biobran/MGN-3 had no effect on the total percentage of NK
      cells, however it enhanced the cytotoxic activity of induced NK cell expression
      of cluster of differentiation 107a, when compared with baseline values and with
      the placebo group (P<0.05). Furthermore, there were no side effects observed,
      indicating that Biobran/MGN-3 supplementation was safe at the utilized dosage and
      for the duration of administration. Various additional beneficial effects were
      observed, including improved mean corpuscular volume and reduced hepatic
      aspartate aminotransferase enzyme levels, which suggested improved liver
      function. It was concluded that Biobran/MGN-3 induces a significant increase in
      NK activity which may increase resistance to viral infections and cancers in the
      geriatric population. However, additional clinical trials should be conducted in
      the future to verify these findings.

PMID- 29456639
TI  - Analysis of effect of 1alpha-hydroxyvitamin D3 on benign paroxysmal positional
      vertigo and risk factors.
AB  - The purpose of this study was to investigate the curative effect of 1alpha
      hydroxyvitamin D3 on the benign paroxysmal positional vertigo (BPPV). Fifty BPPV
      patients diagnosed in the ENT Department of Anzhen Hospital from October 2015 to
      December 2016 were randomly selected as the treatment group, and treated with
      0.25 ug 1alpha-hydroxyvitamin D3 once per day, in addition to the routine
      diagnosis and treatment. Moreover, 50 BPPV patients in the same period were
      selected as the control group, and received the routine diagnosis and treatment.
      The detection results of bone mineral density (BMD) t-value, vitamin D3 and bone
      metabolic markers before and after treatment were compared, and statistical
      analysis was performed on the results. There were no differences in the general
      data between treatment group and control group. There were no statistically
      significant differences in the BMD and age distribution of males and females
      between treatment group and control group (P>0.05). The BMD of male BPPV patients
      in each age group in the treatment group was significantly increased after
      treatment, and the difference was statistically significant (P<0.05). Although
      the BMD of male BPPV patients in each age group in control group was somewhat
      increased after treatment, the difference was not statistically significant
      (P>0.05). The BMD of female BPPV patients in each age group in treatment group
      was increased after treatment, and the difference was statistically significant
      (P<0.05). Similarly, although the BMD of female BPPV patients in each age group
      in control group was somewhat increased after treatment, the difference was not
      statistically significant (P>0.05). The average BMD of female BPPV patients in
      each age group was significantly lower than that of male patients, and the
      difference was statistically significant (P<0.05) (Table II). The BMD t-value of
      patients in treatment group showed a decreasing trend with the increase of age
      (Fig. 1). The levels of 25-hydroxyvitamin D3 and bone metabolic markers in
      treatment group were significantly improved compared with those before treatment
      (P<0.05). Multivariate Logistic regression analysis was performed to identify
      whether the treatment of BPPV was effective or not as a dependent variable, and
      six items, including the sex (female), hypertension, diabetes mellitus, age (>50
      years), 25-hydroxyvitamin D3 and osteopenia/osteoporosis, as the independent
      variables, and the results suggested that the level of 25-hydroxyvitamin D3 and
      osteopenia/osteoporosis are the clinical features of whether the BPPV treatment
      is effective (P<0.05). The results showed that the treatment of BPPV with 1alpha
      hydroxyvitamin D3 can effectively improve the symptoms of patients, and the level
      of vitamin D3 and the occurrence of osteopenia/osteoporosis are the clinical
      indexes of whether the BPPV treatment is effective.

PMID- 29456640
TI  - Comparative study of ultrasonic elastography and conventional ultrasound in
      diagnosis of malignant anus neoplasm.
AB  - The application value of conventional ultrasound and ultrasonic elastography (UE)
      in preoperative diagnosis and combined diagnosis of malignant anus neoplasms was
      investigated. One hundred and twenty patients, whose mass was detected by digital
      rectal examination, were examined using UE and conventional ultrasound before
      operation, and the results were compared with those of histopathological
      examinations after operation, so that the accuracy and imaging features of UE as
      well as UE combined with conventional ultrasound in diagnosing malignant anus
      neoplasm were analyzed. Among the 120 patients, 77 were diagnosed with benign
      lesions and 43 were diagnosed with malignant lesions via pathological diagnosis
      for anal canal lesion surgery. Conventional ultrasound before operation showed
      that 53 patients were diagnosed with benign lesions and 26 with malignant
      lesions. Compared with that in the pathological diagnosis results, the diagnostic
      accordance rate in preoperative conventional ultrasound was 65.8%. Through UE
      diagnosis, 66 patients had benign lesions and 39 patients had malignant lesions.
      Compared with that in the pathological diagnosis results, the diagnostic
      accordance rate in preoperative UE was 87.5%. After the examination via UE
      combined with conventional ultrasound before operation, 71 patients were
      diagnosed with benign lesions and 40 patients were diagnosed with malignant
      lesions; compared with that in the pathological diagnosis results, the diagnostic
      accordance rate was 92.5%. In terms of mass qualitative diagnosis, the
      sensitivity and specificity of conventional ultrasound were 60.5 and 68.8%,
      respectively; those of UE were 90.7 and 85.7%, respectively, and those of UE
      combined with conventional ultrasound were 93.0 and 92.2%, respectively.
      According to the analysis results of receiver operating characteristic (ROC)
      curve, the area under curve (AUC) of malignant anus neoplasm diagnosed via UE was
      0.732 [95% confidence interval (95% CI), 0.211-2.534], the AUC via conventional
      ultrasound was 0.695 (95% CI, 0.517-0.932), and that via UE combined with
      conventional ultrasound was 0.823 (95% CI, 0.146-4.643). In conclusion,
      examinations utilizing UE combined with conventional ultrasound can increase the
      preoperative diagnostic accordance rate in malignant anus neoplasm, which can be
      used as an effective method for preoperative diagnosis of malignant anus
      neoplasm.

PMID- 29456641
TI  - Multiple-site bleeding at pleural adhesions and massive hemothorax following
      percutaneous coronary intervention with stent implantation: A case report.
AB  - An elderly male patient with coronary heart disease underwent coronary
      angiography, which revealed bilateral severe coronary artery stenosis. Four
      stents were implanted, and at 5 h post-surgery, typical hemorrhagic shock
      appeared. Echocardiography verified heavy bleeding in the right thoracic cavity.
      Emergency angiography excluded injury or perforation of the coronary artery,
      aorta, right subclavian artery and brachiocephalic artery. Considering the
      patient's history of chronic obstructive pulmonary disease and severe cough
      during the operation, it was suspected that hemothorax was induced by a blood
      vessel rupture in the pleura. Video-assisted thoracic examination confirmed the
      tearing of pleural adhesion bands and bleeding at three sites in the pulmonary
      pleura and parietal pleura. According to the reported case, bleeding as a result
      of the laceration of pleural adhesions is an important cause of hemothorax that
      should be considered after exclusion of other common causes of pleural
      hemorrhage.

PMID- 29456642
TI  - Anti-Semaphorin-7A single chain antibody demonstrates beneficial effects on
      pulmonary inflammation during acute lung injury.
AB  - Pulmonary inflammation is a primary characteristic of lung injury initiated by
      the accession of immune cells into the alveolar space. Neutrophil migration
      serves an important role in pulmonary inflammation mediated by the migration of
      neutrophils into hypoxic tissue sites. The elimination of pulmonary inflammation
      is directly associated with rehabilitation in patients with lung injury. Anti
      inflammatory treatment is essential following lung injury and ultimately
      determines patient outcomes. Semaphorin-7A (SEMA-7A) is a member of the
      Semaphorin family that influences the migration of neutrophils into hypoxic
      tissue sites, thus promoting inflammation. However, understanding of the role of
      SEMA-7A serves during lung injury is limited and the immunological function of
      SEMA-7A during the migration of neutrophils into acute injury sites remains
      unknown. The present study investigated SEMA-7A expression and constructed a
      single chain antibody for SEMA-7A (Anti-SEMA-7A) to study its therapeutic
      efficacy against pulmonary inflammation in a mouse model of acute injury sites.
      The data indicated that the expression of SEMA-7A was upregulated due to
      induction by pro-inflammatory cytokines and demonstrated that Anti-SEMA-7A
      inhibited SEMA-7A expression in vitro and in vivo. The current study also
      indicated that the production of pro-inflammatory cytokines induced by SEMA-7A in
      endothelial and epithelial cells enhanced pulmonary inflammation. Anti-SEMA-7A
      suppressed the transendothelial migration of neutrophils mediated by SEMA-7A.
      Anti-SEMA-7A treatment neutralized SEMA-7A expression and reduced signs of
      pulmonary inflammation, leading to the elimination of pulmonary inflammation in
      rat with acute lung injury. The current study identified Anti-SEMA-7A as a
      potential agent to interfere with the inflammatory pathway during acute lung
      injury, which may be the basis for anti-inflammatory strategies to treat lung
      injuries in the future.

PMID- 29456643
TI  - Multiple brain abscesses caused by infection with Candida glabrata: A case
      report.
AB  - The present case report described the initial diagnosis of a 25-year old female
      with a brain abscess consisting of two lesions 0.2 and 2.9 cm3 in volume. The
      patient was initially treated with antibiotics; however, 2 months following
      initial treatment, the patient's condition deteriorated and she became
      vegetative. Following transfer to the China-Japan Union Hospital of Jilin
      University (Jilin, China) the two lesions had grown in volume to 9.0 and 13.0
      cm3, respectively. The results of magnetic resonance spectroscopy and plasma 1-3
      beta-D-glucan activity suggested a possible fungal infection. Subsequently, a
      stereotactic biopsy was conducted, fluid was cultured and itraconazole treatment
      was initiated. Analysis of cultures confirmed a Candida glabrata infection and
      antifungal treatment was continued. Shortly following surgery, the patient
      regained consciousness and the ability to eat and speak. A follow-up MRI 8 months
      following biopsy confirmed disappearance of all lesions and no recurrence. To the
      best of our knowledge, this is the first English-language report of a brain
      abscess caused primarily by Candida glabrata.

PMID- 29456644
TI  - Eudesmin attenuates Helicobacter pylori-induced epithelial autophagy and
      apoptosis and leads to eradication of H. pylori infection.
AB  - Eudesmin has been proven to possess anti-inflammatory effects. In the present
      study, the effects of eudesmin on Helicobacter pylori (H. pylori)-mediated
      autophagy, apoptosis, immune response and inflammation were determined in human
      gastric adenocarcinoma (AGS) cells in vitro and in C57BL/6 mice in vivo.
      Detection of the production of interleukin (IL)-8, IL-1beta and immunoglobulin M
      (IgM) was performed using ELISA. Identification of the activation of apoptosis
      associated caspase-3, -8 and -9 proteins, Bcl-2-associated X protein (Bax) and
      BH3 interacting domain death agonist (Bid) protein, was determined through
      western blot analysis. Autophagy microtubule-associated protein 1A/1B-light chain
      3, isoform B (LC-3B) expression was measured using immunostaining. The results of
      the present study demonstrated that eudesmin inhibited the growth of H. pylori,
      with increased inhibition activity against antibiotic resistant strains compared
      with the reference strain. In addition, H. pylori-induced IL-8 secretion, LC-3B
      expression and apoptosis-associated protein (caspase-3, -8 and -9, Bax and Bid)
      activation in AGS cells was suppressed by eudesmin. Furthermore, eudesmin
      suppressed IL-1beta and IgM production in H. pylori-infected C57BL/6 mice in
      vivo. In conclusion, eudesmin may be developed as a promising therapeutic agent
      to prevent and/or treat H. pylori-associated gastric inflammation.

PMID- 29456645
TI  - Influence of exposure to nicotine during pregnancy on the learning and memory for
      adult offspring.
AB  - We aimed to investigate the indirect influence of exposure to nicotine during
      pregnancy on the learning and memory of adult offspring mice. Thirty pregnant C57
      mice were randomly divided into either the control group (CON) or the nicotine
      group (NIC), with 15 mice each. The CON group was given access to drug-free
      water, and the NIC group was given 60 g/ml nicotine in drinking water. Sixteen
      adult mice were randomly selected from the 8 litters for Morris water maze test.
      The level of products of related factors in the hippocampus of mice in the NIC
      and the CON groups were compared using the 1H-MRS method. The escape latency time
      that the adult offspring mice in the NIC group took in the place navigation test
      was significantly longer than that of the CON group. In addition, the NIC group
      took longer time to arrive at the plate than the CON group (P<0.05). mRNA and
      protein levels of NR1 in the hippocampus of the NIC group was significantly
      higher than that in the CON group (P<0.05).alpha7nACh mRNA in the hippocampus of
      the NIC group was not significantly different from that of the CON group
      (P>0.05), while the expression levels of alpha7nACh protein in the hippocampus of
      the NIC group was significantly lower than that in the CON group (P<0.05).
      Detection of protein level of muscarinic receptors in the hippocampus of adult
      offspring mice in the NIC group showed that when compared to the CON group, the
      expression levels of M1, M3, M5 of the NIC group was not significantly different
      from that of the CON group (P>0.05). Therefore, exposure to nicotine during
      pregnancy can cause damage to the learning ability of adult offspring mice but do
      not significantly influence their working memory.

PMID- 29456646
TI  - An experimental rabbit model of symptomatic cerebral vasospasm with in vivo
      neuroimaging assessment and ex vivo histological validation.
AB  - Cerebral vasospasm (CVS) is a severe complication that occurs following
      aneurysmal subarachnoid hemorrhage (SAH). Magnetic resonance angiography (MRA)
      has been used to evaluate brain injury following SAH in humans. The present study
      was designed to assess a rabbit model of symptomatic CVS (SCVS) and the utility
      of MRA in evaluating SCVS in rabbits. Japanese white rabbits (n=24) were randomly
      divided into 2 equal groups: A sham group and a SAH group. Neurological scores
      were evaluated for 7 days following SAH. Basilar artery (BA) diameters were
      measured using MRA preoperatively and 7 days postoperatively. Rabbits were
      sacrificed 7 days following SAH and the BA diameter of each rabbit was determined
      using histological evaluation. Compared with the Sham group, neurological
      function was significantly reduced in the SAH group at all time points (P<0.05).
      Furthermore, the BA diameter was significantly smaller in the SAH group on day 7
      compared with the baseline measurement (P<0.05). No significant difference was
      observed between histological and MRA findings in either group at day 7.
      Histological changes in the hippocampus consistent with ischemia were observed in
      the SAH group. Hippocampal ischemia was also identified in the SAH group via MRA
      and there was no difference in detection rates following the use of MRA and
      histochemistry. MRA appears to be an effective method for assessing vasospasms of
      the BA and ischemic changes to the hippocampus in a rabbit model of SCVS.
      Furthermore, the animal model used in the present study may be beneficial for the
      future study of SCVS.

PMID- 29456647
TI  - Comparison of mono- and combination antibiotic therapy for the treatment of
      Pseudomonas aeruginosa bacteraemia: A cumulative meta-analysis of cohort studies.
AB  - It is currently unknown whether antibiotic monotherapy or combination therapy is
      a more effective treatment for patients with Pseudomonas aeruginosa bacteraemia.
      The present study consists of a systematic review and meta-analysis of cohort
      studies in associated studies. The treatment options of monotherapy and
      combination therapy have been compared, to determine which is more effective
      against P. aeruginosa bacteraemia. Several electronic bibliographic databases
      were systematically searched and clinical studies that compared combination
      therapy with monotherapy for P. aeruginosa bacteraemia were identified.
      Dersimonian and Laird's random-effects models were used to generate summary
      estimates of the effects and to assess their association according to different
      patient characteristics and research quality standards. A total of 17 studies
      were selected, 3 of which were prospective while the remaining 14 were
      retrospective. The studies involved a total of 2,504 patients. Significant
      differences between combination therapy and monotherapy treatment were not found
      when the data were combined (odds ratio (OR)=0.81, 95% confidence interval
      (CI)=0.61-1.08; P=0.035). The results demonstrated strength in a number of
      stratification and sensitivity analyses. The variables used included study type,
      treatment quality score and survival rate of subgroup analysis. To conduct
      cumulative meta-analysis, the number of years and samples were calculated. The OR
      value and 95% CI were stable and demonstrated good change trend. According to the
      size of the sample order following accumulation, OR values and 95% CI (0.89, 0.76
      1.04) exhibited a narrow range. Neither combination therapy or monotherapy
      exhibited significant effects on the mortality of patients with P. aeruginosa
      bacteraemia. Future research is required and should include large, well-designed
      prospective cohorts, and grouped clinical studies.

PMID- 29456648
TI  - Immunosuppressive effects of hydroxychloroquine and artemisinin combination
      therapy via the nuclear factor-kappaB signaling pathway in lupus nephritis mice.
AB  - Lupus nephritis (LN) is one of the most common and severe manifestations of
      systemic lupus erythematosus, leading to permanent renal damage and chronic
      kidney disease. Hydroxychloroquine (HCQ) serves a protective role against lupus
      associated clinical manifestations and medical complications; however, it results
      in numerous adverse reactions, limiting its long-term use. The aim of the present
      study was to investigate the combined effect of HCQ and artemisinin (ART) on LN,
      and to elucidate the underlying mechanisms. An in vivo LN mouse model was
      prepared, and the animals were administered prednisone (PDS; serving as a
      positive control), high-dose HCQ (H-HCQ) or low-dose HCQ combined with ART (L-HCQ
      + ART) once daily for 8 weeks. The body weight, serum biochemical parameters,
      immune and inflammatory indicators, renal and spleen histological alterations,
      and mRNA expression levels of Kruppel-like factor 15 (KLF15) and nuclear factor
      kappaB (NF-kappaB) were analyzed. It was observed that L-HCQ + ART and H-HCQ
      ameliorated the LN-induced body weight decrease, and significantly decreased the
      levels of anti-double stranded DNA, antinuclear antibodies, immunoglobulin G,
      interferon gamma, tumor necrosis factor-alpha and transforming growth factor
      beta1, as well as improved the kidney and spleen pathology, when compared with
      the model group. In addition, L-HCQ + ART and H-HCQ treatments induced KLF15
      upregulation and NF-kappaB downregulation. These results indicated that treatment
      with L-HCQ + ART exerted renoprotective effects by regulating the expression
      levels of cytokines, KLF15 and NF-kappaB. This combination treatment may have a
      similar immunosuppressive effect as PDS and H-HCQ, and may be a promising
      alternative for LN treatment.

PMID- 29456649
TI  - Protective effect of miconazole on rat myelin sheaths following premature infant
      cerebral white matter injury.
AB  - The aim of the present study was to investigate the protective effects of
      miconazole on myelin sheaths following cerebral white matter damage (WMD) in
      premature infant rats. Sprague Dawley rats (3-days-old) were randomly divided
      into four groups (n=30 each) as follows: Sham surgery group, WMD model group, 10
      mg/kg/day treatment group and 40 mg/kg/day treatment group. A cerebral white
      matter lesion model was created by ligating the right common carotid artery for
      80 min. Treatment groups were administered with 10 or 40 mg/kg miconazole at 4-8
      days following birth (early treatment group) or 5-11 days following birth (late
      treatment group). Rats in the model group received the same concentration of
      dimethylsulfoxide. Myelin basic protein (MBP) immunohistochemical staining and
      western blotting were used to detect the expression of cerebral white matter
      specific MBP, and changes in myelin structure were observed using transmission
      electron microscopy. No swelling or necrosis was observed in the corpus callosum
      of the sham group rats, whereas rats in the model group demonstrated edema, loose
      structure, fiber disorder, inflammatory gliocytes and selective white matter
      lesions. Following treatment with miconazole, MBP expression in the corpus
      callosum was significantly higher compared with the model group. Furthermore, in
      the model group, myelin sheaths in the corpus callosum were loose with small
      vacuoles, there was a marked decrease in thickness and structural damage was
      observed. Conversely, a marked improvement in myelination was observed in the
      treatment group. The results of the present study suggest that miconazole is able
      to promote formation of the myelin sheath to ameliorate premature cerebral white
      matter lesions caused by ischemia or hypoxia in rats.

PMID- 29456650
TI  - Application of an acellular dermal matrix to a rabbit model of oral mucosal
      defects.
AB  - Acellular dermal matrices (ADMs) are increasingly used for the restoration of
      soft-tissue defects of the oral cavity due to their ability to facilitate faster
      healing and reduce scar formation without rejection. However, few studies have
      focused on the histopathology and biological mechanisms involved in their use.
      The aim of the present study was to observe tissue growth, histopathologic
      changes and altered biomolecular signatures that occur during the repair of oral
      defects in rabbit models over time, either with or without the employment of ADM.
      Animals were sacrificed 1, 2 and 4 weeks following surgery and histological
      changes were evaluated using hematoxylin and eosin staining. Reverse
      transcription-polymerase chain reaction and western blot analysis were used to
      determine changes in the expression of vascular endothelial growth factor (VEGF)
      and glucose transporter 1 (GLUT1). It was demonstrated that wounds treated with
      ADM exhibited a weak inflammatory reaction and faster epithelialization and
      revascularization compared with untreated wounds. This may have been caused by
      the elevated levels of VEGF and GLUT1 protein detected in the ADM-treated
      defects. Thus, treating wounds of the oral mucosa with an ADM improves
      pathological responses compared with those with an untreated wound. The current
      study demonstrates the underlying mechanisms by which ADM promotes wound healing
      in defects of the oral mucosa and the results provide further evidence for the
      use of ADM in clinical settings for the repair of mucosal defects.

PMID- 29456651
TI  - Protective effect of black garlic extracts on tert-Butyl hydroperoxide-induced
      injury in hepatocytes via a c-Jun N-terminal kinase-dependent mechanism.
AB  - Black garlic has been reported to show multiple bioactivities against the
      development of different diseases. In the present study, the hepatoprotective
      effect of black garlic on injured liver cells was investigated. Rat clone-9
      hepatocytes were used for all experiments; tert-Butyl hydroperoxide (tBHP) was
      used to induce injury of rat clone-9 hepatocytes. The contents of malondialdehyde
      (MDA) and glutathione (GSH); anti-oxidative enzyme activities of catalase (CAT),
      superoxide dismutase (SOD), glutathione peroxidase (GPx); and mRNA expression
      levels of interleukin (IL)-6 and IL-8 in rat clone-9 hepatocytes were determined
      to evaluate the level of cell damage. Black garlic extracts were demonstrated to
      significantly attenuate tBHP-induced cell death of rat clone-9 hepatocytes
      (P<0.05). Pretreatment with black garlic extracts antagonized GSH depletion, tBHP
      increased MDA accumulation and the mRNA expression level of IL-6/IL-8, and tBHP
      decreased antioxidative enzyme activities (all P<0.05). Moreover, the present
      study revealed that c-Jun N-terminal kinase signaling regulated black garlic
      inhibited tBHP effects in rat clone-9 hepatocytes. Our findings demonstrate that
      black garlic has the hepatoprotective potential to block tBHP-damaged effects on
      cell death, lipid peroxidation, oxidative stress, and inflammation in rat clone-9
      hepatocytes. Thus, the present study indicates that black garlic may be an
      excellent natural candidate in the development of adjuvant therapy and healthy
      foods for liver protection.

PMID- 29456652
TI  - Analysis of the levels of Th9 cells and cytokines in the peripheral blood of mice
      with bronchial asthma.
AB  - The purpose of the study was to detect the level of T-helper type 9 (Th9) cells
      and the cytokine interleukin-9 (IL-9) in peripheral blood of mice with bronchial
      asthma, and to explore the relationship between the expression of Th9 cells and
      the pathogenesis of asthma. Thirty female-specific pathogen-free (SPF) Bagg'
      albino (BALB)/c mice were selected and randomly divided into the control group
      (n=15) and the bronchial observation group (n=15). Mice in the bronchial
      observation group were treated with ovalbumin (OVA) for sensitization and
      induction of a mouse model of asthma. The airway reactivity of mice was measured
      by a mouse pulmonary function apparatus using the non-invasive pulmonary
      impedance method. The proportions of Th9 cells in peripheral blood of mice in the
      two groups were detected using flow cytometry. Digital polymerase chain reaction
      (dPCR), enzyme-linked immunosorbent assay (ELISA) and western blot analysis were
      applied to detect the levels of IL-9 messenger ribonucleic acid (mRNA) and
      proteins in peripheral blood and lung tissues of mice in the two groups,
      respectively. Compared with that in the control group, the expression level of
      Th9 cells in the peripheral blood of mice in the observation group was
      significantly elevated (P<0.05), the expression level of IL-9 proteins in the
      peripheral blood was significantly increased (P<0.05), and the levels of IL-9
      mRNA and proteins in lung tissues were significantly increased (P<0.05). The
      results show that the levels of Th9 cells and their cytokine IL-9 in the
      peripheral blood of mice with bronchial asthma are significantly increased,
      suggesting that Th9 cells play important roles in the pathogenesis of asthma.

PMID- 29456653
TI  - Metformin protects against oxidized low density lipoprotein-induced macrophage
      apoptosis and inhibits lipid uptake.
AB  - Oxidized low density lipoprotein (ox-LDL)-induced macrophage apoptosis
      contributes to the formation of atherosclerosis. Metformin, an antidiabetic drug,
      has been reported to attenuate lipid accumulation in macrophages. In this study,
      the effects of metformin on ox-LDL-induced macrophage apoptosis were investigated
      and the mechanisms involved in this process were examined. By performing flow
      cytometry analysis, it was demonstrated that metformin inhibited ox-LDL-induced
      macrophage apoptosis. Increased expression of endoplasmic reticulum (ER) stress
      marker proteins, including C/EBP-homologous protein, eukaryotic translation
      initiation factor 2A, and glucose-regulated protein 78 kDa, induced by ox-LDL was
      also reversed by metformin. Furthermore, ox-LDL-induced cytochrome c (cyto-c)
      release and mitochondrial membrane potential loss were inhibited by metformin. As
      lipid uptake in macrophages contributed to ER stress, cyto-c release and
      mitochondrial membrane potential loss, the mechanisms involved in metformin
      inhibited macrophage lipid uptake were investigated. Expression of scavenger
      receptors, including scavenger receptor A, cluster of differentiation 36 and
      lectin-type oxidized LDL receptor 1 was examined in the presence or absence of
      metformin with ox-LDL treatment. Additionally, the upstream regulatory mechanism
      of scavenger receptors by metformin was also analyzed. In conclusion, metformin
      protects against ox-LDL-induced macrophage apoptosis and inhibits macrophage
      lipid uptake.

PMID- 29456654
TI  - Establishment of different experimental asthma models in mice.
AB  - Asthma is a complex disease. The heterogeneity of airway inflammation during
      asthma indicates there are different mechanisms involved. In order to further
      study the mechanisms of asthma, different mouse models were established to mimic
      corresponding subtypes of asthma in clinic. Eosinophilic asthma was established
      by intraperitoneal injections of ovalbumin (OVA) on day 0 and day 7, followed by
      inhalation of aerosolized OVA on days 14-17. Neutrophilic asthma was established
      by transtracheal administration of a high dose of lipopolysaccharide (LPS; 10 ug)
      on days 15 and 17 in combination with OVA sensitization and challenge as
      described previously. Mix-granulocytic asthma was established by transtracheal
      administration of a low dose of LPS (1 ug) on day 15, in combination with OVA
      sensitization and challenge as described previously. Compared with healthy
      controls, increased numbers of eosinophils, elevated levels of T helper (Th)2
      cytokines in bronchoalveolar lavage fluid (BALF), and moderated inflammation of
      lung tissues was observed in eosinophilic asthma. Increased numbers of
      neutrophils, elevated levels of Th1 and Th17 cytokines in BALF and severe
      inflammation of lung tissues was observed in neutrophilic asthma. Increased
      numbers of both eosinophils and neutrophils, elevated levels of Th1, Th2 and Th17
      cytokines in BALF and severe inflammation of lung tissues was observed in mix
      granulocytic asthma. Airway hyperresponsiveness, increased bronchial mucus
      secretion, and elevated serum levels of immunoglobin (Ig)E and OVA-IgE were
      detected in all three asthma models. Dexamethasone reduced the pathogenic
      symptoms of the mice in eosinophilic asthma, however had no effect on
      neutrophilic asthma or mix-granulocytic asthma. Each model of asthma established
      in the present study represents corresponding subtypes of asthma in clinic.

PMID- 29456656
TI  - Comparison of the diagnostic efficacy between ultrasound elastography and
      magnetic resonance imaging for breast masses.
AB  - The present study compared the efficacy of ultrasound elastography (UE), magnetic
      resonance imaging (MRI) and the combination of the two methods (UE+MRI) in the
      differential diagnosis of benign and malignant breast tumors. In total, 86
      patients with breast masses were recruited and evaluated by UE, MRI and UE+MRI.
      Strain ratios of UE were calculated for the breast mass and adjacent normal
      tissues. In addition, the receiver operating characteristic (ROC) curve was
      obtained, while the sensitivity and specificity were calculated to determine the
      optimal cut-off point for the differential diagnosis. The area under the ROC
      curve (AUC) was also calculated to evaluate the diagnostic performance of these
      methods. The results indicated that the diagnostic accuracy of UE+MRI was
      significantly higher compared with the UE or MRI methods in the differential
      diagnosis of invasive ductal, invasive lobular, intraductal papillary, medullary
      and mucinous carcinomas (all P<0.05). The optimal cut-off points of ROC curve of
      the Strain Ratio in the diagnosis of breast lesions were 2.81, 3.76 and 3.42 for
      UE, MRI and UE+MRI, respectively. Furthermore, the AUC values were 86.7, 79.2 and
      91.4%, while the diagnostic accuracy rates were 82.5, 75.5 and 95.3%, for UE, MRI
      and UE+MRI, respectively. Accuracy rate differences between UE and MRI or between
      UE and UE+MRI were statistically significant (P<0.05), whereas no significant
      difference existed between MRI and UE+MRI (P>0.05). Finally, the diagnostic
      consistency of the UE+MRI method with the pathological diagnosis was higher
      compared with UE or MRI alone. In conclusion, the combination of UE and MRI is
      superior to the use of UE or MRI alone in the differential diagnosis of benign
      and malignant breast masses.

PMID- 29456655
TI  - Effect of immune tolerance induced by immature dendritic cells and CTLA4-Ig on
      systemic lupus erythematosus: An in vivo study.
AB  - Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease in which
      tissue damage is caused by autoantibodies. The induction of specific immune
      tolerance, including the utilization of immune regulatory cells, may enhance the
      therapeutic effects of organ transplantation in patients with SLE. Furthermore,
      inhibiting immune responses has been reported to be an effective treatment for
      SLE. However, few studies have explored the association between an increased
      immune tolerance and a decreased immune response in SLE treatment. Dendritic
      cells (DCs), which are highly efficient antigen-presenting cells, are able to
      induce specific tolerance, while cytotoxic T lymphocyte antigen 4-immunoglobulin
      (CTLA4-Ig) inhibits the immune response. In the present study, interleukin (IL)
      10-treated DCs and CTLA4-Ig were administered to mice with SLE alone or in
      combination and the therapeutic effects were investigated. IL-10 was added into
      the culture medium of bone marrow-derived DCs to prevent them from
      differentiating into mature cells. Low levels of major histocompatibility complex
      II, cluster of differentiation (CD)40, CD80 and CD86 were detected, which
      indicated that the immature state of DCs was maintained. IL-10-treated DCs were
      subsequently injected into the caudal vein of B6.MRL-Faslpr/J lupus mice, which
      are an established animal model of SLE. To amplify the tolerance effect, mice
      were simultaneously injected with CTLA4-Ig. Compared with the IL-10-treated DC
      and CTLA4-Ig groups, combined treatment with IL-10-treated DCs and CTLA4-Ig
      strongly induced immune tolerance in mice with SLE, as indicated by the
      significantly reduced levels of urine protein, anti-nuclear antibody, double
      stranded DNA and IL-17A. A significant decrease in the proportion of T helper
      cells and an increase in the proportion of CD4+ forkhead box protein P3+ Treg
      cells was also observed, further confirming the induction of immune tolerance.
      These results suggest that combined treatment with IL-10-DCs and CTLA4-Ig may be
      a promising novel therapeutic strategy for the treatment of SLE.

PMID- 29456657
TI  - Intramuscular primary immunization by nucleic acid vaccine pcDNA/Gpd-IL-2 and
      enhanced immunization with mucosal adjuvant CpG-ODN and Gpd-IL-2 recombinant
      protein effectively induced strong mucosal immune responses and immune protective
      effects against Treponema pallidum skin infection.
AB  - The present study aimed to evaluate the immune effect of intramuscular primary
      immunization by the nucleic acid vaccine pcDNA/glycerophosphodiester
      phosphodiesterase-interleukin-2 (pcDNA/Gpd-IL-2) and enhanced immunization 2
      weeks later with the combination of mucosal adjuvant CpG-oligodeoxynucleotides
      (ODN) and Gpd-IL-2 recombinant protein on skin infection caused by Treponema
      pallidum (Tp) in New Zealand rabbits. At week 8 following immunization, MTT assay
      was used to detect spleen cell proliferation, while enzyme-linked immunosorbent
      assay was performed to detect the cytokine and secretory immunoglobulin A (SIgA)
      levels. At week 10 after primary immunization, rabbits were inoculated with 105
      Tp (Nichols strain). Alterations in the skin redness, swelling and ulceration
      were recorded for 0-60 days. In addition, positive rate of Tp in skin lesions and
      ulcer formation rate were examined using dark field and silver staining. The
      results indicated that intramuscular primary immunization by nucleic acid vaccine
      pcDNA/Gpd-IL-2 followed by enhanced immunization via nasal feeding with mucosal
      adjuvant CpG-ODN and Gpd-IL-2 recombinant protein induced the higher levels of Tp
      Gpd specific antibodies, increased the secretion of IL-2 and interferon-gamma,
      and promoted the proliferation of T cells in the first 8 weeks after
      immunization. Furthermore, this immunization strategy stimulated the production
      of mucosa specific SIgA antibody. Thus, this strategy led to the lowest Tp
      positive and ulcer formation rates at the Tp infection sites, as well as healing
      of skin lesions on the earliest time point (day 42). In conclusion, immunization
      by nucleic acid vaccine pcDNA/Gpd-IL-2 followed by enhanced immunization with a
      combination of mucosal adjuvant CpG-ODN and Gpd-IL-2 recombinant protein is an
      effective immune strategy to induce strong mucosal immune responses and immune
      protective effects.

PMID- 29456659
TI  - PRMT1-RBM15 axis regulates megakaryocytic differentiation of human umbilical cord
      blood CD34+ cells.
AB  - Protein arginine methyltransferase 1 (PRMT1) serves pivotal roles in various
      cellular processes. However, its role in megakaryocytic differentiation has not
      been clearly reported. The aim of the present study was to explore the role of
      the PRMT-RNA binding motif protein 15 (RBM15) axis in human MK differentiation
      and the feasibility of targeting PRMT1 for leukemia treatment. In the present
      study, PRMT1 was overexpressed and the RBM15 protein was knocked down in human
      umbilical cord blood cluster of differentiation (CD)34+ cells and the cells were
      then cultured in megakaryocytic differentiation medium. Flow cytometry was used
      to analyze CD41 and CD42 double-positive cells, as well as the protein expression
      levels of PRMT1 and RBM15. The results demonstrated that human cord blood CD34+
      cells differentiate into mature MKs in high thrombopoitin medium, as demonstrated
      by CD41 and CD42 expression. Overexpression of PRMT1 in human umbilical cord
      blood CD34+ cells blocked the maturation of megakaryocytic cells. Knockdown of
      RBM15 by short hairpin RNA produced less mature MKs. PRMT1 inhibitor rescued
      PRMT1-blocked megakaryocytic differentiation. These results provide evidence for
      a novel role of PRMT1 in the negative regulation of megakaryocytic
      differentiation. PRMT1 may be a therapeutic target for leukemia treatment.

PMID- 29456658
TI  - Expression of Clara cell 10-kDa protein and trefoil factor family 1 in patients
      with chronic rhinosinusitis and nasal polyps.
AB  - The current study measured the expression of Clara cell 10-kDa protein (CC10) and
      trefoil factor family 1 (TFF1) in the sinus mucosa of patients exhibiting chronic
      rhinosinusitis (CRS) and nasal polyps (NP). CC10 and TFF1 expression in the sinus
      mucosa of the control group and patients with CRS and NP was determined using
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western
      blotting and immunohistochemistry. The correlation between CC10 and TFF1
      expression was further analyzed using Spearman's correlation analysis. The
      expression of TFF1 was significantly increased in the sinus mucosa of patients
      with CRS and NP, whereas CC10 expression was significantly decreased compared
      with controls. Spearman's correlation analysis identified a negative correlation
      between CC10 and TFF1 expression in the sinus mucosa of patients with CRS and NP.
      The results of immunohistochemistry and RT-qPCR were consistent with each other.
      Hematoxylin and eosin staining revealed notable lesions in the mucous membranes,
      goblet cells and cilia of sinus mucosa samples from patients with CRS and NP. The
      negative correlation between CC10 and TFF1 expression during the progression of
      CRS and NP suggest that CC10 and TFF1 may serve important roles in its
      pathogenesis.

PMID- 29456660
TI  - The role of miR-766-5p in cell migration and invasion in colorectal cancer.
AB  - Colorectal cancer (CRC) develops from the colon or rectum and is the fourth
      highest inducer of cancer mortality. In the present study, cancer tissues and
      normal tissues were extracted from patients with CRC who were treated in the
      Affiliated Hospital of Shandong University of Traditional Chinese Medicine
      (Jinan, China). Reverse transcription-quantitative polymerase chain reaction
      demonstrated that the expression level of miR-766-5p was significantly higher
      (P<0.01) in cancer tissue than that in normal tissue. SW480 cells were used for
      in vitro study and randomly separated into the miR-negative control (NC)
      inhibitor treatment group and miR-766-5p inhibitor treatment group. SW480 cell
      behaviors were evaluated. Results demonstrated that in the miR-766-5p inhibitor
      group, there was a decreased level of cell proliferation/migration/invasion and
      higher cell apoptosis compared with that in the miR-NC inhibitor group. miR-766
      5p was predicted and verified to target the 3' untranslated region of suppressor
      of cancer cell invasion (SCAI) in SW480 cells. Protein expression levels of
      matrix metalloproteinase-2/phosphoinositide 3-kinase/AKT were decreased and SCAI
      was increased following miR-766-5p inhibitor treatment. In conclusion, the
      present study indicated that miR-766-5p inhibitor repressed the process of CRC by
      targeting SCAI.

PMID- 29456661
TI  - Anticancer activity of 23,24-dihydrocucurbitacin B against the HeLa human
      cervical cell line is due to apoptosis and G2/M cell cycle arrest.
AB  - Cervical cancer is one of the primary causes of cancer-associated mortality
      worldwide. Due to the increasing incidence of cervical cancer, multiple treatment
      options are required. Initial responses to chemotherapy and surgical
      interventions are generally positive, however patients often experience relapse
      and tumor recurrence. Currently, the effects of cucurbitacins on different types
      of cancer are being investigated, as they exhibit a wide variety of
      bioactivities. The anticancer activity of the cucurbitacin 23,24
      dihydrocucurbitacin B against a panel of human cervical cancer cell lines was
      investigated in the current study. Cell viability was determined using an MTT
      assay and apoptosis was detected using DAPI staining. The proportion of apoptotic
      cells, cell cycle distribution, mitochondrial membrane potential (DeltaPsim) and
      reactive oxygen species (ROS) levels were estimated using flow cytometry. Protein
      expression was determined using western blot analysis. The results of the current
      study indicated that 23,24-dihydrocucurbitacin B inhibited the viability of human
      cervical cancer cell lines and had an IC50 of 40-60 uM. However, its cytotoxic
      effects were much less pronounced in normal epithelial fr2 and HerEpiC cells,
      where it had an IC50 of 125 uM. The underlying mechanisms of this were further
      studied and the results demonstrated that 23,24-dihydrocucurbitacin B induced
      apoptosis in HeLa cells and caused ROS-mediated shifts in the DeltaPsim.
      Additionally, it caused the cell cycle arrest of HeLa cells at the G2/M
      checkpoint. The phosphoinositide 3 kinase/protein kinase B/mechanistic target of
      rampamycin (PI3K/AKT/mTOR) cascade may serve an important role in cancer
      tumorigenesis, progression and resistance to chemotherapy. The results indicated
      that 23,24-dihydrocucurbitacin B significantly decreased the expression of
      important proteins in the PI3K/Akt/mTOR cascade. Taken together, these results
      suggest that 23,24-dihydrocucurbitacin B may be novel method of treating cervical
      cancer.

PMID- 29456662
TI  - MicroRNA profiles of BMSCs induced into osteoblasts with osteoinductive medium.
AB  - MicroRNA (miRNA) plays an important role in cell differentiation and functions as
      a regulator. Therefore, miRNA is important in the process of bone marrow
      mesenchymal stem cells (BMSCs) being induced into osteoblasts. In this study,
      mouse BMSCs were induced with osteoinductive medium, the indices related to
      osteoblastic differentiation were assayed, including alkaline phosphatase, the
      deposit of calcium and protein levels of osteocalcin. Using miRNA microarray and
      reverse transcription-quantitative polymerase chain reaction analyses,
      differentially expressed miRNAs in the cells, which were induced with
      osteoinductive medium, were selected and identified. The target genes of the
      differentially expressed miRNAs were then predicted using bioinformatics
      analysis. The results revealed that osteoinductive medium promoted osteoblastic
      differentiation of BMSCs, and let-7c-5p, miR-181c-3p, miR-3092-3p and miR-5132-3p
      were identified as differentially expressed miRNAs in the cells treated with
      osteoinductive medium for 14 and 21 days. Certain target genes and signal
      pathways related to osteoblastic differentiation of the four miRNAs were
      predicted. These findings indicated the four differently expressed miRNAs may be
      potential regulators of osteoblastic differentiation, providing a basis for
      further study on the regulation of miRNAs in the osteogenic differentiation of
      BMSCs.

PMID- 29456663
TI  - High expression of SDF-1 and VEGF is associated with poor prognosis in patients
      with synovial sarcomas.
AB  - Stromal cell-derived factor-1 (SDF-1) predicts poor clinical outcomes of certain
      types of cancer. Furthermore, vascular endothelial growth factor (VEGF) promotes
      the growth and metastasis of solid tumors. The aim of the present study was to
      examine the expression of SDF-1 and VEGF in patients with synovial sarcoma and to
      determine their expression is correlated with unfavorable outcomes. Levels of SDF
      1 and VEGF proteins were evaluated in 54 patients with synovial sarcoma using
      immunohistochemical and immunofluorescence staining. Potential associations
      between the expression of SDF-1 and VEGF and various clinical parameters were
      analyzed using Pearson's chi2 test and the Spearman-rho test. Additionally,
      univariate and multivariate Cox regression analyses were used to identify
      potential prognostic factors, and the Kaplan-Meier method was used to analyze the
      overall survival rates of patients. Low SDF-1 and VEGF expression was detected in
      20.4% (11/54) and 22.2% (12/54) of patients with synovial sarcoma; moderate
      expression was detected in 35.2% (19/54) and 37.0% (20/54) of patients and high
      expression was detected in 44.4% (24 of 54) and 40.7% (22 of 54) of patients,
      respectively. Levels of SDF-1 and VEGF proteins were significantly associated
      with histological grade (P<0.05), metastasis (P<0.05) and American Joint
      Committee on Cancer staging (P<0.05). In addition, levels of SDF-1 and VEGF
      expression were positively correlated with each other (P<0.001). Univariate
      analysis also indicated that VEGF expression was associated with shorter overall
      survival rates in (P<0.05), whereas multivariate analysis demonstrated that SDF-1
      expression was associated with shorter patient survival rates (P<0.05). Finally,
      both SDF-1 and VEGF expression were associated with various characteristics of
      synovial sarcoma. Therefore, SDF-1 expression may be a potential independent
      prognostic indicator in patients with synovial sarcomas.

PMID- 29456664
TI  - Jinwei Tang modulates HDAC2 expression in a rat model of COPD.
AB  - The aim of the present study was to investigate the effect of a Traditional
      Chinese Herbal Medicine (TCHM), named Jinwei Tang on histone deacetylase 2
      (HDAC2) and its role in the regulation of corticosteroid resistance in a rat
      model of chronic obstructive pulmonary disease (COPD). Male Wistar rats were
      divided into five groups (each n=10): COPD group, established by the
      intratracheal instillation of lipopolysaccharide and passive smoke exposure, and
      control, budesonide, theophylline + budesonide and Jinwei Tang + budesonide
      groups. Lung function was measured, lung tissue histopathology was examined and
      HDAC2 expression in the lung was assessed by immunohistochemistry. In addition,
      protein levels of interleukin-8 (IL-8), tumor necrosis factor (TNF)-alpha and
      HDAC2 in lung homogenate were quantified by ELISA. The rat COPD model exhibited
      alterations of the ratio of forced expiratory volume in 0.2 sec (FEV0.2) to the
      forced vital capacity, FEV0.2, dynamic compliance and airway resistance. HDAC2
      expression was markedly reduced in the lung tissue of the COPD group compared
      with the control group, and treatment with Jinwei Tang + budesonide or
      theophylline + budesonide resulted in significant attenuation of the reduction of
      HDAC2 expression in the lungs (P<0.05). However, treatment with budesonide alone
      did not significantly alter HDAC2 expression. In the Jinwei Tang + budesonide and
      theophylline + budesonide groups, IL-8 and TNF-alpha expression was significantly
      decreased (P<0.05) and the HDAC2 level increased (P<0.05) compared with that in
      the COPD group. In conclusion, Jinwei Tang modulates airway inflammation and may
      enhance the anti-inflammatory effect of glucocorticoid through the upregulation
      of HADC2 expression in a rat model of COPD.

PMID- 29456665
TI  - Involvement of TWEAK and the NF-kappaB signaling pathway in lupus nephritis.
AB  - Previous findings have identified that tumor necrosis factor-related weak inducer
      of apoptosis (TWEAK) is associated with lupus nephritis (LN) activity status;
      however, the mechanism involved remains unclear. The present study aimed to
      investigate the roles of TWEAK and the nuclear factor (NF)-kappaB signaling
      pathway in LN. TWEAK levels in the blood and urine of patients with LN or non-LN
      systemic lupus erythematosus were measured by ELISA and compared with those in
      healthy controls. TWEAK expression and NF-kappaB transcriptional activity in the
      kidney were detected by western blotting, and Ki-67 and cluster of
      differentiation (CD) 68 expression were assessed using immunofluorescence.
      Additionally, human mesangial cells (HMCs) were cultured in vitro and divided
      into five groups: Normal control, TWEAK stimulus group, TWEAK + TWEAK blocking
      antibody, TWEAK + NF-kappaB inhibitor (BAY 11-7082) and TWEAK + combined
      (blocking antibody + BAY 11-7082). Cell cycle activity and Ki-67 expression in
      the HMCs were evaluated using flow cytometry, and cell induction of macrophage
      chemotaxis was determined by a Transwell assay. Levels of the inflammation
      associated factors interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1),
      chemokine ligand 5 (CCL5), IL-8 and IL-10 were also detected by reverse
      transcription-quantitative polymerase chain reaction. It was observed that the
      urine levels of TWEAK in patients with LN were significantly elevated compared
      with those in the other groups (P<0.05). LN kidneys exhibited markedly increased
      cell proliferative ability, macrophage infiltration, TWEAK expression and NF
      kappaB transcriptional activity compared with normal kidneys. Furthermore, the
      results indicated that treatment with recombinant TWEAK notably enhanced NF
      kappaB transcriptional activity and significantly promoted cell proliferation and
      cell cycle activity (P<0.05), induced macrophage chemotaxis (P<0.05),
      significantly increased the expression of the chemotactic factors IL-6, IL-8, MCP
      1 and CCL5 (P<0.05), and significantly reduced anti-inflammatory cytokine IL-10
      mRNA expression in HMCs (P<0.05), relative to normal controls. Accordingly,
      blocking TWEAK function or inhibiting NF-kappaB activity reversed these effects.
      Collectively these data indicate that urine TWEAK may be considered as a novel
      biomarker of LN activity, and that blocking TWEAK function or NF-kappaB activity
      may effectively alleviate glomerular mesangial cell proliferation and macrophage
      chemotaxis.

PMID- 29456666
TI  - MicroRNA-125b-1-3p mediates intervertebral disc degeneration in rats by targeting
      teashirt zinc finger homeobox 3.
AB  - The present study aimed to investigate the association between Teashirt zinc
      finger homeobox 3 (TSHZ3) and the nucleus pulposus (NP) of intervertebral discs
      in rats. TSHZ3 was identified from the differentially expressed micro (mi)RNAs in
      the expression profile of GSE63492 by identifying the overlapped target genes of
      microRNA (miR)-125b-1-3p across different databases. TSHZ3 small interfering RNA
      (siRNA) and an miR-125b-1-3p inhibitor were used for gene silencing and gene
      silencing efficiency was assessed by reverse transcription-polymerase chain
      reaction. Western blotting was performed to detect the cell cycle proteins cyclin
      D1 and B1 and the proteins associated with DNA damage in NP. The results revealed
      that in normal NPs, the expression of TSHZ3 increased following the inhibition of
      miR-125b-1-3p and in DNA damaged NPs, the expression of TSHZ3 was associated with
      the degree of DNA damage. The present study demonstrated that TSHZ3, as a target
      gene of miR-125b-1-3p, may serve a protective role in intervertebral disc
      degeneration and that this protective function may be inhibited by high levels of
      miR-125b-1-3p.

PMID- 29456667
TI  - In vitro study on reversal of ovarian cancer cell resistance to cisplatin by
      naringin via the nuclear factor-kappaB signaling pathway.
AB  - The aim of the present study was to investigate the mechanism of action by which
      naringin reverses the resistance of ovarian cancer cells to cisplatin. Semi
      quantitative reverse transcription polymerase chain reaction (RT-PCR) and western
      blotting assays were used to detect the effects of different concentrations of
      naringin on the expressions of nuclear factor (NF)-kappaB and P-glycoprotein (P
      gp) in the SKOV3/CDDP cell line. Small interfering RNA (siRNA) targeting NF
      kappaB was designed and synthesized to silence NF-kappaB, and recombinant plasmid
      vectors overexpressing NF-kappaB were constructed to transfect cells. RT-qPCR and
      western blotting assays were subsequently performed to detect the effects of NF
      kappaB on the expression of P-gp at the mRNA and protein levels. Naringin was
      added to the NF-kappaB-overexpressing SKOV3/CDDP cells and cultured for 48 h,
      followed by the detection of the expression of P-gp. RT-PCR and western blotting
      results demonstrated that the gene and protein expressions of NF-kappaB and P-gp
      were significantly decreased in a dose-dependent manner by naringin treatment
      (P<0.05). In cells overexpressing NF-kappaB, P-gp expression was significantly
      elevated (P<0.05), and the expression of P-gp was significantly decreased when NF
      kappaB was silenced (P<0.05). Treatment with naringin was able to significantly
      ameliorate the NF-kappaB-induced overexpression of P-gp (P<0.05). These results
      indicate that naringin is able to inhibit the expression of NF-kappaB and P-gp in
      SKOV3/CDDP cells. Such an inhibitory effect may increase gradually with
      concentration, and is associated with blockade of the NF-kappaB signaling
      pathway. This pathway may represent one of the mechanisms of action by which
      Naringin reverses resistance to platinum-based agents in ovarian cancer cells.

PMID- 29456668
TI  - FPOA induces the apoptosis of HepG2 cells.
AB  - The triterpenoid 3-acetoxylanosta-8,24-dien-21-oic acid (FPOA) is isolated from
      the fruiting body of Fomitopsis pinicola. The present study reports that FPOA
      exerts cytotoxic activity and describes the molecular mechanism of FPOA-induced
      apoptosis on human HepG2 hepatoma cells. FPOA exhibited significant cytotoxic
      effects against HepG2, MCF-7 and HeLa cells. However, FPOA was particularly
      cytotoxic towards HepG2 cells, with a half maximal inhibitory concentration value
      of 42.10 uM, thus these cells were taken forward for further analysis. Flow
      cytometry results demonstrated that FPOA significantly increased the apoptotic
      rate of HepG2 cells in a dose-dependent manner, explaining its potent
      cytotoxicity. In addition, western blot analysis revealed that FPOA significantly
      increased the B-cell lymphoma 2 (Bcl-2)-associated X/Bcl-2 ratio, and cytochrome
      c, caspase-9 and caspase-3 release, in addition to significantly decreasing
      poly(ADP) ribose polymerase levels. These observations indicate that FPOA induces
      the apoptosis of HepG2 cells by activating members of the caspase protein family
      and triggering the mitochondrial apoptosis signaling pathway. Based on these
      results, FPOA is a potential agent for the treatment of cancer.

PMID- 29456669
TI  - Expression of DACT1 in children with asthma and its regulation mechanism.
AB  - The aim of the present study was to detect DACT1 expression levels in the lungs
      of children with asthma, and to investigate its role and molecular mechanisms in
      regulating the expression of inflammatory factors in RAW264.7 cells. DACT1, DACT2
      and DACT3 expression was analyzed in biopsy specimens from 10 cases of newly
      diagnosed children with asthma and 10 healthy controls by reverse transcription
      quantitative polymerase chain reaction, and their expression was confirmed in
      RAW264.7 cells. DACT1 expression was silenced by small interfering RNA or
      enhanced by transfection of pcDNA-3.1-DACT1 in RAW264.7 cells, and expression of
      beta-catenin and inflammatory factors, interleukin (IL) 5, IL6 and IL13, was
      analyzed. Nuclear translocation of beta-catenin was detected by western blot
      analysis, and the effect of DACT1 on beta-catenin was investigated with rescue
      experiments. Regulation of the Wnt signaling pathway by DACT1 and beta-catenin
      was analyzed in RAW264.7 cells after recombinant Wnt5A stimulation. DACT1, DACT2
      and DACT3 were significantly upregulated in specimens from children with asthma
      compared with controls (P<0.05) and the expression of DACT1 was significantly
      more increased compared with DACT2 and DACT3 (P<0.05). Inhibition of DACT1
      expression significantly suppressed IL5, IL6 and IL13 mRNA expression levels
      compared with the control (P<0.05), while upregulated DACT1 expression
      significantly increased IL5, IL6 and IL13 mRNA expression (P<0.05). DACT1
      inhibited the expression and nuclear translocation of beta-catenin, while
      overexpression of beta-catenin significantly inhibited the biological function of
      DACT1 (P<0.05). Overexpression of beta-catenin also significantly suppressed the
      upregulation of IL5, IL6 and IL13 mRNA induced by pcDNA3.1-DACT1 transfection
      (P<0.05). Following the addition of Wnt5A, overexpression of DACT1 inhibited the
      expression and nuclear translocation of beta-catenin, and upregulated IL5, IL6
      and IL13 mRNA expression. In conclusion, DACT1 was indicated to be upregulated in
      lung tissues from children with asthma, which could induce higher pro
      inflammatory factor expression. DACT1 may act via inhibiting the expression and
      nuclear translocation of beta-catenin, a factor in the Wnt signaling pathway. The
      present results suggested that DACT1 may be a potential target for the treatment
      of asthma.

PMID- 29456670
TI  - Effect of activated charcoal hemoperfusion on renal function in patients with
      paraquat poisoning.
AB  - The present study retrospectively analyzed 19 patients diagnosed with paraquat
      (PQ) poisoning with the aim to investigate the effect of activated charcoal
      hemoperfusion on renal function and PQ elimination. The results indicated that 7
      patients died and 12 survived. Non-oliguric renal failure occurred in all of the
      7 patients who died. Among the 12 surviving patients, 10 had normal renal
      function and 2 developed non-oliguric renal failure. There was a linear
      correlation between plasma and urine paraquat concentration prior to and during
      activated charcoal hemoperfusion. The equation parameters together with the
      correlation coefficient on admission were as follows: Y=0.5820+1.7348X (R2=0.678;
      F=35.768; P<0.0001). The equation parameters together with the correlation
      coefficient were as follows during activated charcoal hemoperfusion:
      Y=0.6827+1.2649X (R2=0.626; F=50.308; P<0.0001). Therefore, it was concluded that
      in patients with normal renal function, the elimination kinetics of PQ by the
      kidneys were only associated with the plasma PQ concentration. Activated charcoal
      hemoperfusion had little effect on avoiding acute kidney injury in patients with
      severe PQ poisoning.

PMID- 29456671
TI  - Current perspectives of SA-4-1BBL in immune modulation during cancer.
AB  - A recombinant co-stimulatory molecule capable of inducing multiple effects on
      varied immune cells when present in its soluble active form is termed as SA-4
      1BBL. It has been reported to influence innate, adaptive, and regulatory immune
      cells. Recent studies confirmed its engagement with receptor, 4-1BB leading to
      collection of interleukin-2 (IL-2) that in turn overcomes Treg suppression.
      Further, a vast number of pre-clinical studies reported its therapeutic efficacy
      in the form of adjuvant subunit in cancer vaccines. Furthermore, it is also
      observed that it contributes significantly towards communication bridge of CD4
      and NK cells. On the other hand, depletion of either NK or CD4 cells negated SA-4
      1BBL's antitumor protection. The present review article is focused on the current
      updates of this molecule pertaining to the filed of cancer therapeutics or cancer
      preventives.

PMID- 29456672
TI  - Roles of autophagy in androgen-induced benign prostatic hyperplasia in castrated
      rats.
AB  - The present study investigated the role of androgen in the process of androgen
      induced prostate hyperplasia in castrated rats and assessed the role of the
      phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin
      (PI3K/Akt/mTOR) pathway in this process. Furthermore, the extent to which
      autophagy may affect the level of androgen-induced benign prostatic hyperplasia
      was also explored. A total of 40 Sprague Dawley rats were randomly divided into
      four groups: Testosterone group, rapamycin group, 3-methyladenine (3-MA) group,
      and control group. The extent of hyperplasia in prostate tissue the apoptosis and
      autophagy were assayed. The prostate wet weight, volume and index in the
      testosterone group were significantly higher compared with the control group
      (P<0.05) and these factors were significantly lower in the rapamycin group
      compared with the testosterone group (P<0.05). HE staining demonstrated that
      prostate hyperplasia was obvious in the testosterone group. Western blotting
      revealed that caspase-3 levels were higher in the 3-MA group compared with the
      control group and Bcl-2 was higher in the testosterone group compared with the
      control group (P<0.05). Furthermore, in the rapamycin group, Bcl-2 protein
      expression levels were significantly lower than those in the testosterone group
      (P<0.05). The prostate tissue was analyzed using electron microscopy and
      autophagy bodies were identified in the rapamycin group. In the process of
      androgen-induced prostatic hyperplasia in castrated rats, the role of androgen
      may be related to the PI3K/Akt/mTOR signaling pathway. Rapamycin was able to
      inhibit the effect of testosterone and promoted prostate tissue hyperplasia by
      inhibiting the PI3K/Akt pathway. In addition to inhibiting apoptosis in prostate
      cells, androgen was able to induce rat prostate hyperplasia and may also be
      related to the promotion of the proliferation of prostate cells.

PMID- 29456673
TI  - Full-thickness conjunctival flap covering surgery combined with amniotic membrane
      transplantation for severe fungal keratitis.
AB  - Fungal keratitis is a severe and common ocular infectious disease. The present
      study evaluated the efficiency of full-thickness conjunctival flap covering
      surgery with amniotic membrane transplantation (FCCS + AMT) as a transitional
      surgery for severe fungal keratitis. A total of 17 patients with severe fungal
      keratitis without corneal perforation underwent FCCS + AMT between January 2010
      and December 2015. The pathogenic factors, preoperative diagnosis and
      postoperative prognosis of FCCS + AMT at 3 months were evaluated. Subsequently, 7
      patients received sclerokeratoplasty, and the best-corrected visual acuity (BCVA)
      and recurrence ratio were analyzed at 1 month postoperatively. The primary risk
      factor was agricultural trauma (7 cases), followed by a non-agricultural object
      entering the eye (3 cases). Preoperatively, there were 10 cases of fungal
      keratitis positively identified using confocal microscopy and 9 cases positively
      identified by corneal scrapings. A total of 3 months following FCCS + AMT, the
      percentage of cases resulting in preservation of the eyeball was 88.24%, with
      15/17 patients demonstrating complete conjunctival re-epithelization and a smooth
      conjunctival surface without any complications. A total of 2 (11.76%) patients
      experienced melting of the conjunctival flap and development of endophthalmitis,
      and subsequently underwent ocular evisceration surgery. A total of 7 patients
      underwent sclerokeratoplasty and the mean logarithm of the minimum angle of
      resolution BCVA at 1 month was significantly improved (0.689+/-0.121; P<0.001)
      compared with preoperative values (2.459+/-0.037) and BCVA values following FCCS
      + AMT (2.529+/-0.066). No recurrence was observed in any of the cases during the
      follow-up period. Conclusively, FCCS + AMT may be a preferable treatment for
      severe fungal keratitis of the entire corneal ulcer without perforation, and may
      save the eyeball and provide a greater opportunity for corneal transplantation.

PMID- 29456674
TI  - Inflammation responses in patients with pulmonary tuberculosis in an intensive
      care unit.
AB  - Pulmonary tuberculosis caused by Mycobacterium tuberculosis remains a global
      problem. Inflammatory responses are the primary characteristics of patients with
      pulmonary tuberculosis in intensive care units (ICU). The aim of the present
      study was to investigate the clinical importance of inflammatory cells and
      factors for patients with pulmonary tuberculosis in ICU. A total of 124 patients
      with pulmonary tuberculosis in ICU were recruited for the present study. The
      inflammatory responses in patients with pulmonary tuberculosis in ICU were
      examined by changes in inflammatory cells and factors in the serum. The results
      indicated that serum levels of lymphocytes, plasma cells, granulocytes and
      monocytes were increased in patients with pulmonary tuberculosis in ICU compared
      with healthy controls. The serum levels of inflammatory factors interleukin (IL)
      1, IL-6, IL-10, IL-12, and IL-4 were upregulated in patients with pulmonary
      tuberculosis in ICU. Lower plasma concentrations of IL-2, IL-15 and interferon
      gamma were detected in patients with pulmonary tuberculosis compared with healthy
      controls. It was demonstrated that high mobility group box-1 protein expression
      levels were higher in the serum of patients with pulmonary tuberculosis compared
      with healthy controls. Notably, an imbalance of T-helper cell (Th)1/Th2 cytokines
      was observed in patients with pulmonary tuberculosis. Pulmonary tuberculosis
      caused by M. tuberculosis also upregulated expression of matrix metalloproteinase
      (MMP)-1 and MMP-9 in hPMCs. In conclusion, these outcomes demonstrated that
      inflammatory responses and inflammatory factors are associated with the
      progression of pulmonary tuberculosis, suggesting that inhibition of inflammatory
      responses and inflammatory factors may be beneficial for the treatment of
      patients with pulmonary tuberculosis in ICU.

PMID- 29456675
TI  - Correlation between PPAR-alpha methylation level in peripheral blood and
      atherosclerosis of NAFLD patients with DM.
AB  - We investigated the correlation between the methylation levels of peroxisome
      proliferator-activated receptor-alpha (PPAR-alpha) in the peripheral blood and
      atherosclerosis in patients with nonalcoholic fatty liver disease (NAFLD) with
      diabetes mellitus (DM). A total of 50 normal subjects (group N) and 50 NAFLD
      patients with DM (group M) were selected at Qilu Hospital of Shandong University.
      The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein
      (HDL) and low-density lipoprotein (LDL) in groups N and M were detected. The mRNA
      and protein expressions of PPAR-alpha in groups N and M were detected using
      reverse transcription polymerase chain reaction (PCR) and immunofluorescence. The
      differences in expression of PPAR-alpha in group N and M and the correlation
      between PPAR-alpha methylation level and atherosclerosis were analyzed using
      SPSS17.0 statistical software. TC, TG, HDL and LDL in groups N and M were
      significantly different (P<0.01). Hematoxylin and eosin staining showed that the
      histopathological damage was severe in group M. PCR and immunofluorescence showed
      that PPAR-alpha was significantly higher in N than in group M (P<0.01). The
      abnormal expression of PPAR-alpha is closely related to atherosclerosis,
      indicating that the correlation between PPAR-alpha methylation levels in
      peripheral blood and atherosclerosis of NAFLD patients with DM can provide a new
      direction of diagnosis and treatment.

PMID- 29456676
TI  - Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive
      pulmonary disease.
AB  - Cordyceps sinensis is a traditional Chinese herbal medicine that has been used
      for centuries in Asia as a tonic to soothe the lung for the treatment of
      respiratory diseases. The aim of the present study was to determine the effects
      of C. sinensis on airway remodeling in chronic obstructive pulmonary disease
      (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were
      orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5
      g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung
      inflammation and airway remodeling were evaluated. C. sinensis treatment
      significantly ameliorated airway wall thickening, involving collagen deposition,
      airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in
      model rats with COPD. Additionally, C. sinensis administration in rats with COPD
      reduced inflammatory cell accumulation and decreased inflammatory cytokine
      production, including tumor necrosis factor-alpha, interleukin-8 and transforming
      growth factor (TGF)-beta1 in bronchoalveolar lavage fluid. Meanwhile, the
      increased levels of alpha-smooth muscle actin and collagen I in the COPD group
      were also markedly decreased by C. sinensis treatment. Furthermore, compared with
      untreated rats with COPD, C. sinensis reduced the expression level of
      phosphorylated (p)-Smad2, p-Smad3, TGF-beta1 and its receptors, with the
      concomitant increased expression of Smad7 in the lungs of rats with COPD. These
      results indicated that treatment with C. sinensis may be a useful approach for
      COPD therapy.

PMID- 29456677
TI  - Concurrent eosinophilia and IgG4-related disease in a child: A case report and
      review of the literature.
AB  - The current study presents the case of a 9-year-old Chinese boy who presented
      with eosinophilia and elevated serum levels of immunoglobulin G4 (IgG4). A bone
      marrow puncture identified an elevated eosinophil rate of 23% (normal range,
      <5%), which indicated eosinophilia. However, gene analysis, fluorescent in situ
      hybridization and other examinations, including bone marrow aspiration, blood
      routine, auto-antibody tests and parasitic and allergens screening, contradicted
      a diagnosis of secondary or clonal eosinophilia. Furthermore, the patient
      exhibited multiple lymph node swelling and a lymph biopsy strongly indicted a
      pathological diagnosis of IgG4-related disease (IgG4-RD). His peripheral blood
      flow cytometry confirmed an elevated count of plasmablasts, which is specific to
      IgG4-RD. The patient responded well to therapy with prednisone and remained
      healthy in all follow-ups. By taking all these factors into consideration, the
      boy was diagnosed with IgG4-RD. It is difficult to distinguish IgG4-RD from
      hypereosinophilic syndrome and the potential association between the two remains
      unclear. However, the present case study serves as a reminder that IgG4-RD may
      occur in children and medical professionals should not neglect this possibility.

PMID- 29456678
TI  - Association between DSCR4 gene methylation in plasma in early pregnancy and
      Down's syndrome.
AB  - Down's syndrome (DS), a chromosomal abnormal genetic disease caused by a local or
      total copy of chromosome 21, leads to patients suffering from delayed body
      growth, special facies, mild to moderate mental retardation and other symptoms,
      seriously affecting the life of patients. The aim of the present study was to
      examine the association between Down's syndrome critical region 4 (DSCR4) gene
      methylation in plasma in high-risk pregnant women with DS in early pregnancy
      (hereinafter referred to as pregnant women in early pregnancy) and DS, in order
      to screen new epigenetic markers for the clinical diagnosis of DS. DNA in
      peripheral blood cells and plasma in pregnant women in early pregnancy were
      treated with hydrosulphite. DSCR4 genes with different methylation levels were
      amplified by methylation-specific polymerase chain reaction (PCR), and the
      methylation difference of the CpG site of the DSCR4 amplification product in
      peripheral blood DNA was verified via restriction endonuclease analysis. The
      expression of DSCR4 with different methylation levels in peripheral blood of
      pregnant women in early pregnancy were detected via reverse transcriptase
      quantitative PCR (RT-qPCR), and the DSCR4 gene functions were studied via the
      intervention in DSCR4 expression with small interfering RNA (siRNA). Methylation
      specific PCR and restriction endonuclease analysis revealed that DSCR4 genes were
      differentially methylated in peripheral blood DNA in pregnant women in early
      pregnancy. Additionally, DSCR4 showed a low methylation status in plasma but a
      high methylation status in peripheral blood cells. RT-qPCR revealed that non
      methylated DSCR4 was highly expressed in the peripheral blood of pregnant women
      in early pregnancy, and thus was an epigenetic marker of fetal DS. siRNA results
      showed that the downregulation of DSCR4 inhibited cell migration and invasion,
      but had no effect on cell proliferation. The results suggest that the DSCR4 gene
      was differentially methylated in peripheral blood DNA in pregnant women in early
      pregnancy. Furthermore, DSCR4 exists in a non-methylated state in plasma and in a
      hyper-methylated state in blood cells. DSCR4 can therefore promote the migration
      and invasion of trophocytes and serve as an epigenetic marker of non invasive
      clinical diagnosis of DS.

PMID- 29456679
TI  - miR-98 inhibits cell proliferation and induces cell apoptosis by targeting MAPK6
      in HUVECs.
AB  - The aim of current study was to explore the role of microRNA (miR)-98 in
      atherosclerosis. Human vascular endothelial cells (HVECs) were isolated from the
      peripheral blood of healthy volunteers and patients with atherosclerosis.
      Compared with endothelial cells from the healthy control group, the expression
      level of mitogen activated protein kinase (MAPK)6 was significantly upregulated
      and miR-98 was downregulated in the endothelial cells of patients with
      atherosclerosis. The human umbilical vein endothelial cell line (HUVEC) was
      adopted to perform in vitro studies. Overexpression of miR-98 reduced the
      proliferation and induced the apoptosis of HUVECs, which were revealed using an
      MTT assay, and flow cytometry assay, respectively. The aforementioned influences
      of miR-98 on HUVECs were mediated by targeting MAPK6, which was verified using
      luciferase assays. Additionally, the overexpression of miR-98 reduced the protein
      level of apoptosis regulator Bcl-2 and MAPK6; however, it induced the protein
      expression of caspase-3 and apoptosis regulator Bax. In conclusion, these
      findings demonstrate that miR-98 is an important regulator of atherosclerosis,
      suggesting that miR-98 may be a potential therapeutic target for the treatment of
      atherosclerosis.

PMID- 29456680
TI  - Correlation of vitamin D receptor with bronchial asthma in children.
AB  - This study was designed to investigate the correlation of vitamin D receptor
      (VDR) gene polymorphism with bronchial asthma in children. Seventy patients
      admitted to Daqing Longnan Hospital and diagnosed as bronchial asthma for the
      first time from April 2015 to May 2017 were selected as observation group.
      Patients received routine treatment and intervention. Seventy healthy subjects
      admitted to hospital during the same period were enrolled as the control group.
      Vitamin D gene polymorphism was detected by polymerase chain reaction-restriction
      fragment length polymorphism assay; the levels of total serum immunoglobulin E
      (IgE) in the two groups were determined by electrochemiluminescence immunoassay;
      lung function levels in patients were measured using PowerCube (Germany)
      pulmonary function instrument before and after treatment, and the relationship
      between VDR gene polymorphism and lung function in children with bronchial asthma
      was analyzed. The difference in comparison of base frequency of rs1544410 locus
      of VDR gene had no statistical significance between the two groups (P>0.05). The
      locus CC frequency of rs7975232 of VDR gene in observation group was lower in the
      observation group than that in the control group (P<0.05); the locus AC and AA
      frequencies of rs7975232 of VDR gene were higher in the observation group than
      those in the control group (P<0.05). The level of vitamin D was lower in the
      observation group than that in the control group (P<0.05); the level of total
      serum IgE was higher in the observation group than that in the control group
      (P<0.05). The forced expiratory volume in 1 sec (FEV1), peak expiratory flow
      (PEF) and the ratio of FEV1 to forced vital capacity (FVC) in children with
      bronchial asthma in the observation group were higher after treatment than those
      before treatment (P<0.05). The correlation research displayed that VDR gene
      polymorphism was negatively correlated with lung function levels in children with
      bronchial asthma (P<0.05). The results showed that children with bronchial asthma
      are often accompanied by different degrees of changes in VDR gene polymorphism,
      which is negatively correlated with the severity of asthma, so vitamin D should
      be strengthened to ameliorate the prognosis of children.

PMID- 29456681
TI  - Analysis of related factors of surgical treatment effect on 215 patients with
      laryngeal cancer.
AB  - This study investigated the factors affecting the surgical treatment effect on
      patients with laryngeal cancer. The clinical data (including the sex, age,
      smoking index, drinking, primary tumor site, tumor (T) stage, lymph nodes (N)
      stage, tumor differentiation degree, tumor diameter, surgical method, lymph node
      metastasis and cervical lymph node dissection) of 215 patients with laryngeal
      cancer in The Central Hospital of Wuhan were analyzed retrospectively; the
      survival rate was calculated using the Kaplan-Meier method; log-rank test was
      used for single-factor analysis, while Cox proportional hazard regression model
      was used for multiple-factor analysis. The 215 patients were followed up after
      surgical treatment. The 1-, 3- and 5-year survival rates were 96.2, 78.0 and
      72.5%, respectively. The results of single-factor analysis showed that the age,
      primary tumor site, tumor differentiation degree, T stage, N stage, smoking
      index, tumor diameter and lymph node metastasis had significant influence on the
      postoperative curative effect on patients (P<0.05), but the patient's age,
      drinking and surgical method had no correlation with the postoperative curative
      effect (P>0.05). Multiple-factor analysis revealed that the primary tumor site, T
      stage, N stage and lymph node metastasis were the independent risk factors
      affecting the surgical effect on patients with laryngeal cancer. The survival
      rate of laryngeal cancer is decreased with the increase of T stage and N stage.
      The survival rate of patients with supraglottic laryngeal cancer is higher than
      that of patients with glottic laryngeal cancer and subglottic laryngeal cancer,
      and the survival rate of patients with lymph node metastasis-positive laryngeal
      cancer is lower than that of patients with lymph node metastasis-negative
      laryngeal cancer. The main factors affecting the survival rate of laryngeal
      cancer are primary tumor site, T stage, N stage and lymph node metastasis.

PMID- 29456682
TI  - L1CAM promotes epithelial to mesenchymal transition and formation of cancer
      initiating cells in human endometrial cancer.
AB  - Identification of novel factors critical for epithelial to mesenchymal transition
      (EMT) and cancer initiating cell (CIC) formation may aid in the identification of
      novel therapeutics for the treatment of endometrial cancer. The present study
      demonstrated that L1 cell adhesion molecule (CAM) is critical for EMT and
      formation of CICs in endometrial cancer. Overexpression of L1CAM may promote EMT
      with increased formation of CICs in HEC-1A endometrial cancer cells. CICs and
      mesenchymal status resist chemotherapeutic drugs and may regenerate the various
      cell types in tumors, thereby resulting in relapse of the disease. The present
      study demonstrated that overexpressing L1CAM promoted paclitaxel resistance and
      regulated paclitaxel resistance-associated microRNA expression in HEC-1A cells.
      Furthermore, it was demonstrated that overexpressing L1CAM promoted anoikis
      resistance in HEC-1A cells. This link between L1CAM and EMT/CICs may provide a
      novel target for advancing anticancer therapy.

PMID- 29456683
TI  - Carbenoxolone inhibits mechanical stress-induced osteogenic differentiation of
      mesenchymal stem cells by regulating p38 MAPK phosphorylation.
AB  - The aim of the present study was to explore the effects of pannexin1 (Px1)
      protein channels on osteogenic differentiation of mesenchymal stem cells (MSCs)
      under mechanical stress stimulation. MSCs were isolated from Sprague Dawley rats
      (3 weeks old, weighing 100-120 g) and cultured in vitro. A safe concentration of
      carbenoxolone was determined (CBX, an inhibitor of Px1 channels; 100 uM) on MSCs
      using the Cell Counting Kit-8 (CCK8) method. MSCs were divided into 6 groups:
      Control, stress (4,000 u strain), and stress following 3, 6, 12, and 24 h
      pretreatment with CBX. Stress groups were stimulated with mechanical stress for
      15 min. Alkaline phosphatase (ALP) activity, type I collagen expression,
      intracellular calcium ion (Ca2+) concentration, Px1 expression, p38 mitogen
      activated protein kinase (MAPK) and extracellular signal-regulated
      phosphorylation were determined. ALP activity was increased in the stress group,
      and this was prevented by pretreatment with CBX. Similarly, stress-induced
      increases in type I collagen expression, Ca2+ concentration, Px1 expression, and
      p38 MAPK phosphorylation decreased in the presence of CBX. ERK phosphorylation
      was decreased by stress, however was not affected by CBX treatment. Altogether,
      the results suggest that mechanical stress promoted the osteogenic
      differentiation of MSCs, and this promotion was inhibited by pretreatment with
      CBX, possibly through regulating the phosphorylation of p38 MAPK.

PMID- 29456684
TI  - CAPN3, DCT, MLANA and TYRP1 are overexpressed in skin of vitiligo vulgaris
      Mexican patients.
AB  - Vitiligo is a disorder causing skin depigmentation, in which several factors have
      been proposed for its pathogenesis: Environmental, genetic and biological aspects
      of melanocytes, even those of the surrounding keratinocytes. However, the lack of
      understanding of the mechanisms has complicated the task of predicting the
      development and progression. The present study used microarray analysis to
      characterize the transcriptional profile of skin from Vitiligo Vulgaris (VV)
      patients and the identified transcripts were validated using targeted high
      throughput RNA sequencing in a broader set of patients. For microarrays, mRNA was
      taken from 20 skin biopsies of 10 patients with VV (pigmented and depigmented
      skin biopsy of each), and 5 biopsies of healthy subjects matched for age and sex
      were used as a control. A signature was identified that contains the expression
      pattern of 722 genes between depigmented vitiligo skin vs. healthy control, 1,108
      between the pigmented skin of vitiligo vs. healthy controls and 1,927 between
      pigmented skin, depigmented vitiligo and healthy controls (P<0.05; false
      discovery rate, <0.1). When comparing the pigmented and depigmented skin of
      patients with vitiligo, which reflects the real difference between both skin
      types, 5 differentially expressed genes were identified and further validated in
      45 additional VV patients by RNA sequencing. This analysis showed significantly
      higher RNA levels of calpain-3, dopachrome tautomerase, melan-A and tyrosinase
      related protein-1 genes. The data revealed that the pigmented skin of vitiligo is
      already affected at the level of gene expression and that the main differences
      between pigmented and non-pigmented skin are explained by the expression of genes
      associated with pigment metabolism.

PMID- 29456685
TI  - miR-372 promotes breast cancer cell proliferation by directly targeting LATS2.
AB  - MicroRNAs (miRs) have previously been demonstrated to be important in the
      tumorigenesis and progression of breast cancer. miR-372 was previously revealed
      to be involved in various types of human cancer, however its function in breast
      cancer remains largely unknown. The present study demonstrated that miR-372 is
      frequently overexpressed in breast cancer cell lines and tissues. The
      downregulation of miR-372 markedly inhibited cell proliferation, arrested the
      cell cycle in the G1/S phase, and increased the apoptosis of breast cancer cells.
      Consistently, an in vivo xenograft study also demonstrated the suppressive
      effects of miR-372 knockdown on tumor growth. Further studies revealed that miR
      372 modulated the expression of large tumor suppressor kinase 2 (LATS2) by
      directly targeting its 3'-untranslated region in breast cancer cells.
      Furthermore, silencing of LATS2 was able to rescue the effect of the miR-372
      inhibitor. Overall, the results suggest that miR-372 functions as an oncogenic
      miRNA in breast cancer by targeting LATS2.

PMID- 29456686
TI  - Biochanin A extirpates the epithelial-mesenchymal transition in a human lung
      cancer.
AB  - The natural iso-flavonoid, biochanin A, is categorized as a phytoestrogen and has
      been demonstrated to exhibit various pharmacological properties. However, no
      effects of biochanin A on lung cancer cell lines have been reported. Therefore,
      the present study aimed to demonstrate whether biochanin A has the ability to
      reduce lung cancer triggered pro-inflammatory effects from leukemic monocytes. We
      studied the release of cytokines, tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-6, from the cocultured cells of A427:AML-193. In addition to
      this, epithelial-mesenchymal transition was also monitored. In the cocultured
      A427 and AML-193, AML-193 was stimulated by A427 cells assisting the release of
      TNF-alpha and IL-6 cytokines, but the addition of A427 with biochanin A reduced
      A427-triggered generation of cytokines by AML-193. Moreover, this non-functional
      A427:AML-193 coculture reduced the metastasis effects of A427 cells, as
      determined by wound healing assays and migration/invasion assays. These results
      were further confirmed by a reduction in Snail and E-cadherin expression levels,
      which are indicators of the epithelial-mesenchymal transition. These findings
      suggest the therapeutic effect of biochanin A against lung cancer evoked
      inflammation and pro-inflammatory functions from monocytic cells.

PMID- 29456687
TI  - Girdin protein: A potential metastasis predictor associated with prognosis in
      lung cancer.
AB  - The present study explored the relationship between Girdin protein expression and
      the survival rate of patients with lung carcinoma. A total of 334 lung cancer
      specimens, 20 benign lung disease tissue sections and 24 fresh tissues from
      patients with lung carcinoma were analyzed by immunohistochemistry and western
      blotting. Girdin protein was expressed in 130/334 (38.93%) of the cases examined.
      Girdin protein expression was correlated with tumor/node/metastasis stage
      (P<0.001), lymph node metastasis (P=0.001), distant metastasis (P<0.001) and
      specimen sites (P=0.034). Girdin expression was also correlated with signal
      transducer and activator of transcription 3 (STAT3) expression (P<0.001).
      Patients with high Girdin and STAT3 expression had a significantly poorer
      prognosis compared with those with low/high, high/low or low/low expression
      (P<0.001). In summary, Girdin may be a prognostic marker of lung cancer and serve
      as a biomarker for metastasis.

PMID- 29456688
TI  - Overexpression of microRNA-506-3p aggravates the injury of vascular endothelial
      cells in patients with hypertension by downregulating Beclin1 expression.
AB  - The aim of the present study was to measure the expression of microRNA (miRNA)
      506-3p in the peripheral blood of patients with hypertension and to determine the
      biological functions and mechanisms of action of miR-506-3p. A total of 61
      patients with primary hypertension were included in the present study. Peripheral
      blood was collected from all patients, as well as 31 healthy subjects who were
      included in a control group. The expression of miR-506-3p in peripheral blood was
      determined by reverse transcription-quantitative polymerase chain reaction. Human
      umbilical vein endothelial cells (HUVECs) were transfected with miR-506-3p mimics
      or miR-506-3p inhibitor. The proliferation and migration of HUVECs were
      determined using cell-counting kit 8 and Transwell assays, respectively. The cell
      cycle and apoptosis of HUVECs were detected by flow cytometry. The expression of
      Beclin1 (BECN1) protein, a potential target of miR-506-3p, was measured using
      western blotting. A dual-luciferase reporter assay was performed to determine the
      interaction between BECN1 and miR-506-3p. It was demonstrated that miR-506-3p
      expression in the peripheral blood of patients with patients was upregulated and
      dependent on the severity of hypertension. miR-506-3p overexpression inhibited
      the proliferation and migration of HUVECs. In addition, miR-506-3p inhibited the
      transition from the G1 phase to the S-phase in HUVECs. Overexpression of miR-506
      3p promoted the apoptosis of HUVECs. Notably, miR-506-3p downregulated the
      expression of BECN1 by directly binding to its 3'-untranslated region. The
      present study demonstrated that miR-506-3p expression is elevated in the
      peripheral blood of patients with hypertension and is associated with the
      severity of hypertension. By downregulating BECN1 expression, miR-506-3p
      aggravates injury in vascular endothelial cells by inhibiting the proliferation
      and migration of HUVECs, as well as promoting their apoptosis.

PMID- 29456689
TI  - Inhibition of the Ras/Raf/extracellular signal-regulated kinase 1/2 signaling
      pathway by compounds of natural origin for possible treatment of spinal cord
      injury: An in silico approach.
AB  - Spinal cord injury (SCI) is a severe disease associated with permanent
      neurological deficit. Recent studies in the treatment of SCI have demonstrated
      that the Ras/Raf/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling
      pathway serves an important role in the disease etiology, and that upregulation
      of this signaling pathway is associated with the development of SCI. In the
      present study, inhibition of Ras protein was employed in order to downregulate
      the Ras/Raf/ERK1/2 signaling pathway using compounds of natural origin from the
      Interbioscreen natural compound database. To the best of our knowledge, this is
      the first study using a chemical-computational approach in order to identify
      novel small molecule inhibitors for Ras. A database of ~50,000 compounds was
      selected for virtual screening, setting a free energy binding bias of -7 kcal/mol
      to limit the number of compounds. The subset of compounds generated by virtual
      screening was further limited by subjecting these to the Lipinski's rule of five
      parameters. A total of five shortlisted compounds were subjected to molecular
      docking simulation. The compounds were docked into the GTP binding site of Ras,
      and the inhibition of this site was examined as a promising strategy for the
      downregulation of Ras/Raf/ERK1/2 signaling pathway. The compounds bound to the
      GTP binding site through hydrogen bonds and hydrophobic interactions. The
      identified lead compound was then subjected to molecular dynamics simulation, and
      the results revealed that GLY60 in the GTP binding site of Ras protein was the
      optimal binding site during a 100 nsec run.

PMID- 29456690
TI  - Protective effects of recombinant human brain natriuretic peptide in
      perioperative period during open heart surgery.
AB  - The aim of the present study was to evaluate the protective effects and safety
      aspects of recombinant human brain natriuretic peptide (rhBNP) on cardiac
      functions of patients undergoing open-heart surgery during perioperative period.
      In total, 150 patients undergoing open heart surgery in the Second Hospital of
      Shandong Universty from August 2015 to July 2016 were randomly divided into
      control group and observation group each with 75 cases. Patients in control group
      were treated by routine rehabilitation while patients in the observation group
      were treated by both the routine rehabilitation and rhBNP. All the observations
      were made before operation, after operation and 7 days after operation. The
      changes of N-terminal pro-brain natriuretic peptide (NT-proBNP) of patients, the
      left ventricular ejection fraction (LVEF), cardiac function [Cardiac output (CO),
      pulmonary capillary wedge pressure (PAWP) and central venous pressure (CVP)] of
      patients were measured. Further, respirator support time, ICU stay time,
      incidence of complications and vital signs (BP, HR, SaO2) of patients in the two
      groups were also compared. NT-proBNP levels of all patients improved after
      operation but it decreased in both groups after 7 days of operation. The decrease
      of NT-proBNP levels in observation group was significantly higher than that of
      control group. Whereas, LVEF, CO, PAWP and CVP of patients in both the groups
      increased after operation but effects were significantly higher in the
      observation group after 7 days of medication. Respirator support time and ICU
      stay time of patients in observation group were significantly shorter than those
      in control group, and the incidence of postoperative complications of patients in
      the observation group were significantly lower than the control group. Moreover,
      BP, HR and SaO2 of patients in observation group were significantly elevated in
      comparison to control group (P<0.05). Recombinant human brain natriuretic peptide
      (rhBNP) could significantly improve the cardiac functions of patients after open
      heart surgery, and is safe as well as reliable.

PMID- 29456691
TI  - Different doses of folic acid and vitamin B12 to treat rabbits with deep venous
      thrombosis and hyperhomocysteinemia.
AB  - The effects of different doses of folic acid and vitamin B12 on rabbits with deep
      vein thrombosis (DVT) and hyperhomocysteinemia were investigated. In total, 60
      New Zealand rabbits were divided into untreated control, low-dose and high-dose
      groups. After inducing DVT, hemorheology and coagulation indexes were measured 3
      and 10 days later. We found that both treatment groups performed better than the
      control group, and the high-dose performed better than the low-dose. Ten days
      after thrombosis, the levels of Hcy and D-dimer were lower in the high-dose
      group. Moreover, the changes of lower extremity deep venous thrombosis were
      significantly reduced in both high- and low-dose groups, but the high-dose group
      showed the most improvement. The effective rate of the high-dose group was 100%,
      higher than the rate in the low-dose and control groups. Overall, high-dose of
      folic acid and vitamin B12 can significantly improve plasma Hcy, coagulation
      indexes, and pathological changes in the venous thrombosis of the lower
      extremity.

PMID- 29456692
TI  - Effects of Th17/Treg cell imbalance on HIV replication in patients with AIDS
      complicated with tuberculosis.
AB  - The purpose of this study was to determine the effect of Th17/Treg cell imbalance
      on HIV replication in patients with AIDS complicated with tuberculosis (TB). We
      selected 32 patients with AIDS combined with TB infection in our hospital and 30
      healthy individual as controls. The Th17/Treg ratio in peripheral blood
      lymphocytes was detected by flow cytometry. Compared with healthy subjects, Th17
      cells first declined in HIV patients with TB, but gradually increased over the
      course of the disease. Treg showed an increasing trend in HIV patients with TB.
      The Th17/Treg ratio was significantly altered as the condition gradually
      deteriorated. ELISA showed that interleukin (IL)-17, IL-6 and IL-10 in patients
      with HIV complicated with TB were significantly lower than in healthy subjects.
      The imbalance of Th17/Treg cells can promote HIV virus replication in AIDS
      patients with TB infection, which can aggravate the condition.

PMID- 29456693
TI  - Seminal bacterial composition in patients with obstructive and non-obstructive
      azoospermia.
AB  - A number of culture-dependent and -independent studies have reported that the
      number and significance of bacterial species in semen may have been
      underestimated. The aim of the present study was to profile the seminal
      microbiome in patients with obstructive or non-obstructive azoospermia. A high
      throughput sequencing method was adopted to sequence genomic DNA extracted from
      the semen of healthy people (C group), patients with obstructive azoospermia (OA
      group) and patients with non-obstructive azoospermia (NOA group). The results
      revealed that Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria
      species comprised the majority of bacteria in the C (98.14%), OA (98.26%) and NOA
      (90.96%) groups. Patients in the OA and NOA groups exhibited an increase in
      Bacteroidetes and Firmicutes, whereas the number of Proteobacteria and
      Actinobacteria were decreased compared with the C group. A total of 398 common
      operational taxonomic units were identified, of which 27 belonged to the genus
      Lactobacillus. Furthermore, Phylogenetic Investigation of Communities by
      Reconstruction of Unobserved States analysis indicated that the pathogenic
      species and reduced biodiversity in the semen of patients with azoospermia may
      result in an increased risk of metabolic, infectious and immune diseases. In the
      present study, the seminal microbiome of patients with obstructive or non
      obstructive azoospermia was explored, which may be useful for developing novel
      treatments against azoospermia as well as for its diagnosis.

PMID- 29456694
TI  - Correlation of expression levels of caspase-3 and Bcl-2 in alveolar lavage fluid
      in neonatal respiratory distress syndrome and prognosis.
AB  - This study was designed to investigate the correlation between expression levels
      of cysteine aspartic protease-3 (caspase-3) and B-cell lymphoma gene-2 (Bcl-2)
      proteins in alveolar lavage fluid and the prognosis of infants with neonatal
      respiratory distress syndrome (RDS). A total of 150 infants with neonatal RDS
      undergoing alveolar lavages were divided into four groups: RDS1 (group A, n=42),
      RDS2 (group B, n=38), RDS3 (group C, n=38) and RDS4 (group D, n=32) according to
      their thoracic X-ray film grading. The oxygen uptake score, oxygenation
      saturation, mean airway pressure and expression levels of caspase-3 and Bcl-2 in
      alveolar lavage fluid of the infants in the four groups were measured and
      compared. Our results showed higher grading by thoracic X-rays in patients with
      increased oxygen uptake score, oxygenation index, mean airway pressure, caspase-3
      expression level, hospital stay, complications and death rates in all groups;
      however, the expression levels of Bcl-2 were decreased in those cases, and the
      differences had statistical significance among the four groups (P<0.05). Analyses
      for correlation showed a caspase-3 positive area that was positively correlated
      with oxygen uptake score, oxygenation index and mean airway pressure (P<0.05);
      and a Bcl-2 expression level that was negatively correlated with oxygen uptake
      score, oxygenation index and mean airway pressure (P<0.05). Based on our
      findings, the severity of neonatal RDS is positively correlated with the
      concentration of caspase-3 in alveolar lavage fluid, and negatively correlated
      with the expression level of Bcl-2.

PMID- 29456695
TI  - A comparative study of the single-site laparoscopic herniorrhaphy using needle
      instruments and double-site laparoscopic herniorrhaphy in the minimally invasive
      treatment of inguinal hernias in children.
AB  - The clinical effect of the single-site laparoscopic herniorrhaphy (SSLH) using
      needle instruments and double-site laparoscopic herniorrhaphy (DSLH) in the
      treatment of inguinal hernias in children were compared. A total of 1,010
      children with inguinal hernias who were treated in Chao-Yang Hospital from March
      2011 to December 2014 were selected. According to the operation method, these
      children were divided into the single-site group using needle instruments (n=508)
      and the traditional double-site group (n=502). The clinical indexes of the two
      groups were compared. All the clinical indexes (operation time, intraoperative
      blood loss, time of off-bed and discharge time) in the single-site group using
      needle instruments were significantly lower than those in the traditional double
      site group (P<0.001, <0.001, <0.001 and <0.003, respectively), but the incidence
      rates of postoperative complications and contralateral occult hernia were at the
      similar level (P=0.249 and 0.221, respectively), so the difference was
      statistically insignificant. Patients in the two groups were followed up for 2
      years and there was no recurrece in children in the single-site group while there
      was 2 in the double-site group. The SSLH using needle instruments is more
      effective with fewer traumas in the treatment of inguinal hernias in children
      than the DSLH. It is easier for children to recover from the herniorrhaphy with
      no scars, so it conforms more closely to the concept of minimally invasive
      herniorrhaphy, which can be promoted and applied for the treatment of inguinal
      hernias in children.

PMID- 29456696
TI  - Infectious mononucleosis and hepatic function.
AB  - Abnormal hepatic function is common in infectious mononucleosis (IM). However, it
      remains unknown why increased transferase levels are more common than bilirubin
      abnormalities in IM. The current study aimed to investigate these associations in
      the Chinese population. A total of 95 patients with IM (47 males and 48 females)
      were enrolled in the current study, as well as 95 healthy controls. Patients were
      sorted by sex. A receiver operating characteristic (ROC) curve was used to
      determine cut-off values for IM diagnosis and prediction. Crude and adjusted odds
      ratios (OR) for IM were analyzed using binary logistic regression. It was
      determined that alanine aminotransferase (ALT), aspartate aminotransferase (AST)
      and gamma-glutamyl transferase (GGT) levels were significantly higher in patients
      with IM compared with controls; however, total bilirubin (TB) levels were
      significantly lower in patients with IM. ROCs demonstrated that, if ALT, AST and
      GGT concentrations were higher than, or if TB was lower than, cut-off values,
      they were predictive of IM. Binary logistic regression identified that the risk
      of IM in patients exhibiting high levels of transferases was significantly
      increased, particularly in males. Crude ORs in ALT quartile 4 were 21.667 and
      10.111 for males and females, respectively and adjusted ORs were 38.054 and
      9.882, respectively. A significant IM risk of IM was evident in patients with low
      bilirubin levels and females appeared to be particularly susceptible. For
      example, crude ORs in quartile 1 were 8.229 and 8.257 for males and females,
      respectively and adjusted ORs were 8.883 and 10.048, respectively. Therefore, the
      current study identified a positive association between transferase levels and IM
      and a negative association between TB and IM. Therefore, the results of the
      current study indicate that high transferases are suggestive of IM, particularly
      in males, whereas low TB is suggestive for IM, particularly in females.

PMID- 29456697
TI  - Relationship between fat mass and obesity-associated gene expression and type 2
      diabetes mellitus severity.
AB  - This study sought to investigate any correlation between fat mass and obesity
      associated gene (FTO) expression and the severity of type 2 diabetes mellitus
      (T2DM). In total 110 patients newly diagnosed with T2DM in the outpatient
      department of Yantai Yuhuangding Hospital between September 2016 and March 2017
      were selected as study subjects and were divided into severe (58 cases) and mild
      groups (52 cases) according to T2DM severity. Patients in the severe group were
      followed up for 12 weeks. An additional 60 healthy individuals were selected to
      serve as the normal control group. Fasting plasma glucose (FPG), fasting insulin
      (FINs), fasting C-peptide (FCP), glycosylated hemoglobin (HbA1c) and homeostasis
      model assessment of insulin resistance (HOMA-IR) were examined for every patient
      in the study. Real-time polymerase chain reaction (RT-PCR) was used to detect FTO
      messenger ribonucleic acid (mRNA) expression levels in patient peripheral blood
      lymphocytes. Western blotting was used to detect serum FTO protein expression
      levels, upon which the correlation between FTO protein levels and all other
      indices were analyzed. Compared with the normal control group, both T2DM groups
      showed significantly increased waist circumferences, hip circumferences, body
      mass indexes (BMIs), blood glucose indexes (FPG, FCP, HbA1c, FINs, HOMA-IR) and
      FTO mRNA/protein levels (p<0.05). Additionally, the increases presented by the
      severe T2DM group were significantly greater than those presented by the mild
      T2DM group (p<0.05). After 12 weeks of treatment, the severe T2DM group showed
      decreased BMI, blood glucose index and FTO protein expression (p<0.05). FTO
      protein expression in T2DM patients was higher than in healthy controls, with
      severe patients showing greater expression levels than mild group patients. FTO
      expression was positively correlated with BMI, waist circumference, chest
      circumference, FPG, FCP, HbA1c, FINs and HOMA-IR. Therefore, FTO expression can
      serve as a marker for the clinical diagnosis and treatment of T2DM.

PMID- 29456698
TI  - Correlation of blood glucose, serum chemerin and insulin resistance with NAFLD in
      patients with type 2 diabetes mellitus.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a form of clinical syndrome
      characterized by the fatty degeneration in liver histology and should be further
      investigated. The aim of the study was to investigate the effects of blood
      glucose, serum chemerin and insulin resistance on non-alcoholic fatty liver
      disease (NAFLD) in patients with type 2 diabetes mellitus to provide a basis for
      the prevention and treatment thereof. In total, 300 patients with type 2 diabetes
      mellitus treated and admitted into the Endocrinology Department of our hospital
      from June 2015 to June 2017 were enrolled and divided into the simple type 2
      diabetes mellitus (group A) and concurrent NAFLD (group B) groups. The sex, age,
      body mass index (BMI), blood pressure, blood biochemical indexes and chemerin
      level were compared between the two groups. The patients in group B were further
      divided into the mild fatty liver (group B1), moderate fatty liver (group B2) and
      severe fatty liver (group B3) groups. The sex, age, BMI blood pressure, blood
      biochemical indexes and chemerin level were also compared among the three groups.
      Finally, the risk factors of type 2 diabetes mellitus complicated by NAFLD were
      analyzed via logistic regression. The BMI, fasting plasma glucose (FPG), 2 h post
      prandial plasma glucose (2hPG), triglyceride (TG), total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-c), alanine aminotransferase (ALT), fasting
      insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) and
      HOMA-beta indexes and serum chemerin level in group B were significantly higher
      than those in group A (P<0.05 or P<0.01). Notably, the aggravation of NAFLD, the
      aforementioned indexes were obviously increased (P<0.05 or P<0.01). The
      regression analysis revealed that BMI, FPG, TC, LDL-c, FINS, HOMA-IR and chemerin
      were risk factors of concurrent NAFLD. Thus, type 2 diabetes mellitus complicated
      by NAFLD is closely associated with severe glucose-lipid metabolism disorder and
      insulin resistance, and BMI, FPG, TC, LDL-c, FINS, HOMA-IR and chemerin
      constitute risk factors of concurrent NAFLD.

PMID- 29456699
TI  - Correlation between survivin polymorphism and acute leukemia of children.
AB  - The correlation between the variations in the polymorphic sites of survivin,
      rs9904341C/G and rs8073069C/G, and the pathogenesis of acute leukemia, as well as
      the guiding significance in clinical practice were investigated. We enrolled a
      total of 182 children with acute leukemia and 200 healthy children as the
      subjects. In accordance with the case-control method, the polymerase chain
      reaction was carried out for genetic typing of the two polymorphic sites,
      rs9904341C/G and rs8073069C/G. In the case group and the healthy group, the
      frequencies of C and G alleles in rs9904341C/G of survivin were 59.3 and 41.7%,
      and 46.7 and 50.3%, respectively, and the pairwise comparison showed
      statistically significant differences (P=0.008). Additionally, the frequencies of
      genotypes, C/C, C/G and G/G, were 38.5 and 41.7%; 19.8 and 26.5%; 16.5 and 27.0%
      in the case group and the healthy group, respectively, and the differences in
      comparisons showed statistical significance (P=0.033). The genotype frequency of
      C/C in the case group was 38.5%, significantly higher than that in the healthy
      group (26.5%). Compared with C/C, the risk coefficient of leukemia in patients
      with genotypes of C/G or G/G was significantly decreased. In the case group and
      the healthy group, the frequencies of C and G alleles in rs8073069C/G of survivin
      were 30.5 and 69.5%; 27.7 and 72.3%, respectively, and the pairwise comparison
      showed no statistically significant differences (P=0.404). Additionally, the
      frequencies of genotypes, C/C, C/G and G/G, were 11 and 39.0%; 50.0 and 9.0%;
      37.5 and 53.5% in the case group and the healthy group, respectively, and the
      differences in comparisons showed no statistical significance (P=0.62). Compared
      with the genotype of C/C, we found that the risk of leukemia was not affected in
      patients with genotypes of C/G and G/G. In conclusion, the SNP of rs9904341C/G in
      survivin may be correlated with the risk of acute leukemia, and compared with C/C
      genotype, patients with C/G or G/G may have a decreased risk of acute leukemia.
      In survivin, rs8073069C/G may have no correlation with the risk of acute
      leukemia.

PMID- 29456700
TI  - Effects of HIV on metabolic and biological pathways of CD4+ T lymphocytes.
AB  - The effects of human immunodeficiency virus (HIV) on the metabolic and biological
      pathways of cluster of differentiation (CD)4+ T lymphocytes were investigated. A
      total of 150 patients with acquired immune deficiency syndrome (AIDS) and 50
      healthy individuals who were admitted to hospital for physical examination during
      the period of June 2016 to January 2017, were selected as subjects in the present
      study. According to the virus load, 150 AIDS patients were divided into three
      groups: i) Viral load >106 copies/ml (group A, n=39), ii) 104 copies/ml < viral
      load <105 copies/ml (group B, n=76), and iii) viral load <104 copies/ml (group C,
      n=35). The relationship between viral loads in the three groups and CD4+ T
      lymphocyte counts was assessed. Active lymphocytes were isolated from T
      lymphocytes in the subjects, and the ratio of Th1 to Th2 was measured by flow
      cytometry. Effects of HIV on human T-lymphocyte differentiation were observed.
      Differences in T-lymphocyte metabolites were detected by proton nuclear magnetic
      resonance and their biological pathways analyzed. The results showed that CD4+ T
      cell counts were decreased with the increase of the viral loads of patients. The
      viral loads of AIDS patients differentiated T lymphocytes. In other words, high
      viral loads accelerated the differentiation of T lymphocytes into Th1 cells. In
      the high HIV viral load group, the levels of glycerol phosphodiesterase, 7
      dehydrocholesterol, p-hydroxyphenylacetic acid, cholesterol and deoxyuridine were
      increased, but the levels of 3-methoxytyramine, cytidine deaminase,
      deoxycorticosterone and 3-hydroxybutyric acid were decreased. The viral loads of
      AIDS patients are associated with CD4+ T-cell counts and the ratio of CD4+ T to
      CD8+ T cells. At the same time, HIV viral loads can affect the lipid biosynthesis
      of T-lymphocyte membranes, thus affecting the differentiation and proliferation
      of T lymphocytes and finally intervening its mediated immune responses.

PMID- 29456701
TI  - Correlation between cortisol levels and concurrent infection for hepatitis B
      cirrhosis patients and countermeasure analysis.
AB  - The study assessed the correlation between cortisol (COR) levels and concurrent
      infection for the patients with hepatitis B cirrhosis for corresponding
      countermeasure analysis. In total, 86 patients with hepatitis B cirrhosis (non
      infection group) and 32 patients with hepatitis B cirrhosis complicated with
      infection (infection group) who were diagnosed and treated in the Beijing YouAn
      Hospital from March 2014 to March 2017 were selected. The fasting venous blood of
      all the patients was drawn to detect COR, cortisol binding globulin (CBG), blood
      routine indexes, C-reactive protein (CRP), procalcitonin (PCT), endotoxin and
      other indicators. The relative expression of CBG mRNA was detected by reverse
      transcription quantitative polymerase chain reaction (RT-qPCR). The differences
      and correlation of COR levels between the infection and non-infection groups were
      compared and analyzed. The concentrations of COR and CBG were decreased with the
      increase of Child-Pugh grade, and the difference was statistically significant
      (P<0.05). COR, CBG and free cortisol (FC) concentrations with the same Child-Pugh
      grade in the non-infection group were higher than those in the infection group
      (P<0.05). COR, CBG and FC concentrations of abdominal infection complicated with
      sepsis or abdominal infection complicated with pulmonary infection were lower
      than those of simple abdominal infection (P<0.05). The relative expression of CBG
      mRNA was detected by RT-qPCR, which also showed that: for Child-Pugh grade, grade
      A > grade B > grade C (P<0.05), non-infection group > infection group (P<0.05),
      abdominal infection + sepsis group and abdominal infection + pulmonary infection
      group were lower than the simple abdominal infection group (P<0.05). The values
      of white blood cells (WBC), neutrophils, CRP, PCT and endotoxin in the infection
      group were higher than those in the non-infection group, and the differences were
      statistically significant (P<0.05). COR, CGB and FC were negatively correlated
      with inflammatory indexes such as WBC, neutrophils, CRP, PCT and endotoxin. The r
      value of COR and FC in the non-infection group was 0.678, while that of OR and FC
      in the infection group was 0.787. COR was positively correlated with FC before
      and after infection. The results of the study show that the cortisol levels of
      patients with hepatitis B cirrhosis are significantly correlated with whether
      infected or not, levels of disease condition and infection types, and can be used
      as sensitive indicators of hepatitis B cirrhosis infection.

PMID- 29456702
TI  - Application of pre-injection of dexmedetomidine of different doses in pediatric
      intravenous general anesthesia without tracheal intubation.
AB  - This study observed the clinical efficacy of pre-injection of dexmedetomidine of
      different doses before surgery and the adverse reactions during the recovery
      period in pediatric intravenous general anesthesia without tracheal intubation.
      Pediatric patients who received general anesthesia without tracheal intubation
      before surgery from January 2016 to March 2017 were randomly divided into four
      groups (n=30), and were respectively treated with intravenous pump infusion of
      loaded dexmedetomidine of high-dose (2.5 ug/kg), middle-dose (1.5 ug/kg) and low
      dose (0.5 ug/kg), while the children in the control group received injection of
      normal saline in same dose. Then, the mean arterial pressure (MAP) at different
      time points (5 and 10 min after administration, after anesthesia and after
      surgery), heart rate, Ramsay sedation score changes and adverse reactions during
      recovery period of anesthesia of pediatric patients were compared among four
      groups. At 5 and 10 min after administration, Ramsay scores of high-dose group
      and middle-dose group were higher than that of the control group, and the
      differences had statistical significance (P<0.05). There was no significant
      difference in comparison of Ramsay scores between low-dose group and the control
      group. The MAP and heart rate after anesthesia and after surgery of pediatric
      patients with pump infusion of dexmedetomidine in the three groups were decreased
      significantly compared to those of the control group, and the differences had
      statistical significance (P<0.05). The incidence rate of adverse reaction of
      pediatric patients during the recovery period after pump infusion in the three
      groups and the control group was, respectively, 13/30, 8/30, 7/30 and 8/30, and
      the differences were statistically significant (P<0.05). The sedative effect and
      safety of pre-injection of dexmedetomidine in pediatric intravenous general
      anesthesia without tracheal intubation are promising, and the medium dosage can
      maximize the anesthetic effect with less side effects.

PMID- 29456703
TI  - Silencing of TGIF sensitizes MDA-MB-231 human breast cancer cells to cisplatin
      induced apoptosis.
AB  - The present study was designed to explore the sensitivity of MDA-MB-231 cells to
      cisplatin after silencing the expression of TG-interacting factor (TGIF) protein.
      Cell viability was measured using an MTT assay. Cell apoptosis was detected by
      the annexin V and dead cell assay and the Hoechst staining assay. Protein
      expression was analyzed using western blot analysis. A colony formation assay was
      also performed. It was observed that cisplatin reduced the expression of TGIF
      protein in a dose- and time-dependent manner. Silencing TGIF significantly
      suppressed the cell proliferation and colony formation in MDA-MB-231 cells with
      the treatment of cisplatin. Results indicated that silencing TGIF could
      dramatically increase the cisplatin-induced apoptosis rate in MDA-MB-231 cells.
      The expression of PARP and caspase-3 proteins was correlated with the effect that
      silencing TGIF enhanced cisplatin sensitivity in MDA-MB-231 cells. The present
      data showed that silencing TGIF promoted apoptotic sensitivity that was induced
      by cisplatin in MDA-MB-231 human breast cancer cells and suggested that TGIF
      might be a therapeutic target for improving the chemotherapy response in triple
      negative breast cancer.

PMID- 29456704
TI  - Optimal method of gold nanoparticle administration in melanoma-bearing mice.
AB  - The present study assessed different methods of administering gold nanoparticles
      (GNPs) using different formulations to determine which of the methods achieved
      optimal radiosensitization. Cells from the B16F10 mouse melanoma cell line were
      implanted in the femoral area of mice, assigned to one of the eight following
      groups: i) Control; ii) intravenous (IV) injection of polyethylene glycol (PEG)
      binding GNPs (Peg-GNPs) alone; iii) direct intratumoral (IT) injection of Peg
      GNPs alone; iv) radiotherapy (RT)-alone; v) Peg-GNP IV + RT; vi) Peg-GNP IT + RT;
      vii) naked GNP (N-GNPs) IV + RT; and viii) N-GNP IT + RT. Injection volumes of
      the Peg-GNPs (particle size, 15 nm; dose, 2.8 mg/ml) and N-GNPs (particle size,
      15 nm; dose, 200 mg Au/cc) were 0.3 and 0.2 ml per mouse, respectively, for IV
      and IT. The femoral area was irradiated with a single dose of 10 Gy. To evaluate
      the effects of GNPs, the current study measured the changes in the tumor volume
      ratio to the initial tumor volume over time and observed the survival rate.
      Administration of GNPs with RT did not improve the suppression of tumor growth or
      survival to a statistically significant extent. The administration of Peg-GNPs
      alone indicated a slight tumor suppressing effect at the early stage. The current
      study was not able to confirm the radiosensitization effect of GNPs in melanoma
      bearing mice with tumors that were large in comparison to previous studies.
      Further research is required to validate the radiosensitizing effect on large
      tumors.

PMID- 29456705
TI  - Discrimination of malignant transformation from benign endometriosis using a near
      infrared approach.
AB  - The aim of the present single-center retrospective study was to investigate the
      discrimination of malignant transformation from ovarian endometrioma (OE) using a
      near-infrared approach ex vivo. Cystic fluid samples were collected from patients
      with OE (n=34) and endometriosis-associated ovarian cancer (EAOC) (n=12). The
      light reflected from each sample of cystic fluid [change in luminance, Deltal
      (cd/m2) = background luminance-cystic fluid luminance at 800 nm] was spectrally
      measured by a near-infrared CCD camera with band-path filter (800 nm). The Deltal
      in EAOC was significantly lower compared with that in OE. On regression analysis,
      a positive correlation was observed between the Deltal and Hb level in the cystic
      fluid, and this association was exponential. The diagnostic sensitivity and
      specificity of Deltal was 83.3 and 94.1% at the cutoff value of 21.5 cd/m2, with
      an area under the ROC curve of 0.897. The present ex vivo study potentially
      provides a powerful near-infrared approach for quantitative discrimination
      between EAOC and benign OE, with high sensitivity and specificity, which may have
      clinical applications.

PMID- 29456706
TI  - Comparison of single- and triple-injection methods for ultrasound-guided
      interscalene brachial plexus blockade.
AB  - Ultrasound-guided interscalene brachial plexus blockade (IBPB) has a relatively
      high success rate in shoulder surgery; however, whether multiple injections are
      superior to a single injection (SI) is currently unknown. In the present study,
      ultrasound-guided SI and triple-injection (TI) IBPBs were compared in a
      prospective randomized trial. A total of 111 patients undergoing arthroscopic
      shoulder surgery and presenting with an American Society of Anesthesiologists
      physical status grading of I-II were randomly allocated to receive IBPB with 15
      ml of 1% ropivacaine as a SI or TI. Performance time, procedure-related pain
      scores, success rate and prevalence of complications were recorded. The
      distribution of sensory and motor block onset in the radial, median, ulnar and
      axillary nerves were assessed every 5 min until 30 min post-local anesthetic
      injection. The duration of sensory and motor blocks were also assessed. A
      significantly longer performance time was recorded in the TI group (P<0.001). No
      significant difference was observed in success rate (91% in TI vs. 88% in SI) 30
      min post-injection, and the prevalence of complications and procedure-related
      pain were similar between the two groups. Sensory and motor blocks of the ulnar
      nerve in the TI group were significantly faster and more successful compared with
      the SI group at all time points (P<0.041). It was also observed that sensory and
      motor blocks in the TI group were prolonged compared with the SI group (P<0.041).
      In conclusion, the TI method exhibited a faster time of onset and resulted in a
      more successful blockade of the ulnar nerve. TI method may be a more effective
      approach for IBPB in a clinical setting.

PMID- 29456707
TI  - Resveratrol induces autophagic apoptosis via the lysosomal cathepsin D pathway in
      human drug-resistant K562/ADM leukemia cells.
AB  - The aim of the present study was to investigate the crosstalk between resveratrol
      (Res)-induced autophagy and apoptosis, and the molecular pathway by which
      autophagy leads to apoptotic death in drug-resistant K562/ADM leukemia cells. The
      viability of K562/ADM cells was determined using the MTT assay. The formation of
      autophagic vacuoles was detected using transmission electron microscopy and
      monodansylcadaverine (MDC) staining. Cell apoptosis was evaluated using flow
      cytometry. The expression of apoptosis- or autophagy-associated proteins was
      measured using western blotting. The results indicated that treatment with Res
      inhibited cell viability in a concentration-dependent manner. Furthermore, the
      numbers of MDC-positive fluorescent points, autophagic vacuoles and autolysosome
      engulfed cytoplasmic materials were markedly increased in Res-treated K562/ADM
      cells compared with untreated cells, as determined using fluorescence microscopy
      and transmission electron microscopy. Res-induced apoptosis was associated with
      increased cleaved caspase-3 and B-cell lymphoma 2 associated X protein, and
      decreased B-cell lymphoma 2 (Bcl-2) protein expression levels when compared with
      the control (P<0.05). However, the proportion of apoptotic cells decreased from
      69.6 to 41.0% (40 umol/l Res) and from 77.3 to 58.8% (80 umol/l Res) following
      pre-treatment with the autophagy inhibitor 3-methyladenine (P<0.01). The protein
      expression levels of microtubule-associated protein 1A/1B-light chain 3 and
      beclin 1, two markers of autophagy, were upregulated in Res-treated cells
      compared with the control (P<0.05). In addition, lysosomal cathepsin D (Cath D)
      release increased during Res-induced autophagy and apoptosis (P<0.05). The
      present results demonstrated that Res-induced apoptosis of K562/ADM cells was
      autophagy-dependent and the released Cath D may trigger caspase-dependent cell
      death through the Bcl-2 family of proteins. Furthermore, the present data
      indicate that to enhancement of the autophagy-cathepsin-apoptosis pathway may be
      an effective approach for overcoming anticancer drug resistance.

PMID- 29456708
TI  - Meniscal allograft transplantation using a novel all-arthroscopic technique with
      specifically designed instrumentation.
AB  - The present study describes a novel all-arthroscopic technique for medial and
      lateral meniscal allograft transplantation (MAT). Surgical instruments were
      specifically designed to assist in the all-arthroscopic approach for MAT. The
      bone plug attachment technique, either the arthroscopic-assisted or all
      arthroscopic approach, attaches bone plugs to the anterior and posterior horns.
      In the present study, two sets of surgical implements were designed: One to
      produce bone plugs of predefined sizes in the anterior and posterior horns of the
      allograft meniscus (bone plug implements) and a second to create bone tunnels in
      the receptor tibial plateau to hold the bone plugs (bone tunnel implements). The
      present study demonstrated that an all-arthroscopic approach to MAT was feasible.
      Furthermore, the specifically designed surgical instruments allowed for
      consistent preparation of grafts and recipient tissues, contributing to a
      standardized approach to MAT. The present findings indicate that an all
      arthroscopic approach to MAT may be achievable. They also provide the incentive
      for future clinical studies to directly compare the outcomes and to initiate the
      standardization of the procedure to optimize MAT and maximize patient outcomes
      and quality of life.

PMID- 29456709
TI  - Anterior spinal instrumentation combining a prosthetic disc nucleus with a
      flexible stabilization device: Manufacture and use in intervertebral disc repair.
AB  - Artificial disc replacement alone is unable to completely cure cervical
      degenerative diseases; thus, a stabilization device markedly improves patient
      recovery. In order to meet this requirement, an anterior spinal instrumentation
      combining a prosthetic disc nucleus with a flexible stabilization device (ASI
      combining PDN/FD) was developed. An artificial disc was designed and manufactured
      using polyvinyl alcohol hydrogel (PVA-H) with a repeated freeze-melting
      technique, and subsequently the dehydration and swelling properties of the PVA-H
      were investigated. A canine animal model was then used to compare the differences
      in the degeneration of cervical discs adjacent to the operative segment with
      PDN/FD against a plate fixation system, without the interferences of brace
      intensity, which was ensured by pressure monitoring the dog's intervertebral disc
      adjacent to operative segments. The in vivo results demonstrated a clear decrease
      in the degeneration of the adjacent disc with the use of PDN/FD as compared with
      the plate fixation system. In conclusion, PDN/FD may offer a promising method for
      the treatment of cervical degenerative disease.

PMID- 29456710
TI  - Mechanism of apoptosis induction associated with ERK1/2 upregulation via
      goniothalamin in melanoma cells.
AB  - The present study aimed to investigate the effect of goniothalamin on apoptosis
      induction in the A375 melanoma cell line. Melanoma is a type of skin cancer with
      increased prevalence and no potential standard treatment. Goniothalamin is a
      plant, bioactive styrly-lactone, which has various bioactivities including anti
      microbial, anti-inflammatory and anti-cancer. Apoptosis induction by
      goniothalamin has been studied in numerous cancer cell lines, however not in the
      melanoma cell line A375. The results of the MTT assay demonstrated that
      goniothalamin induced anti-proliferation in a dose dependent manner. Hoechst
      staining assay demonstrated that goniothalamin induced chromatin condensation and
      apoptotic bodies in A375 treated cells, and JC-1 staining revealed that
      goniothalamin induced mitochondrial membrane dysfunction in A375 cells. In
      addition, goniothalamin decreased the level of anti-apoptotic proteins myeloid
      cell leukemia 1, B cell lymphoma (Bcl)-2 and Bcl-extra large, whereas it
      increased the level of pro-apoptotic proteins, Bcl-2 Associated X, apoptosis
      regulator, t-BID and Bim in A375 treated cells. In addition, goniothalamin also
      increased active caspase-9, -7 and cleaved-poly (ADP-ribose) polymerase
      expression in A375 treated cells. Furthermore, phosphorylated (p)-pyruvate
      dehydrogenase kinase (PDK) 1 (Ser241) and p-RAC-alpha serine/threonine-protein
      kinase (Akt; Ser473) were decreased, however c-Jun and p-extracellular signal
      regulated kinase (ERK)1/2 were increased upon goniothalamin treatment. These
      results suggest that goniothalamin has an effect, as anti-proliferation and
      apoptosis induction in A375 cells were associated with upregulated p-ERK1/2, c
      Jun and downregulated p-PDK1 (Ser241), p-Akt (Ser473) in A375 cells. Therefore,
      goniothalamin may be a potential candidate for anti-cancer drug development for
      melanoma treatment.

PMID- 29456711
TI  - Value of the albumin-bilirubin score in the evaluation of hepatitis B virus
      related acute-on-chronic liver failure, liver cirrhosis, and hepatocellular
      carcinoma.
AB  - The aim of the present study was to investigate the value of the albumin
      bilirubin (ALBI) score in the assessment of the disease conditions of hepatitis B
      virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF), HBV-related liver
      cirrhosis (HBV-LC) and HBV-related hepatocellular carcinoma (HBV-HCC). A total of
      395 patients with HBV-ACLF, HBV-LC, or HBV-HCC were retrospectively studied. The
      ALBI, Child-Turcotte-Pugh (CTP), and Model for End-Stage Liver Disease (MELD)
      scores of the patients were calculated, and the relationships between the ALBI
      score and the CTP and MELD scores were investigated. Furthermore, the ALBI
      grading was tested for the evaluation of the severity and stages of HBV-ACLF, HBV
      LC, and HBV-HCC, especially when classifying the clinical stages of HBV-ACLF. The
      mean ALBI scores of the HBV-ACLF, HBV-LC, and HBV-HCC patients were -1.17+/-0.55,
      -1.76+/-0.66 and -2.59+/-0.62, respectively; the mean CTP scores were 10.70+/
      1.81, 8.19+/-1.25 and 5.81+/-1.22, respectively; and the mean MELD scores were
      19.93+/-7.44, 11.10+/-4.39 and 7.01+/-3.22, respectively. The ALBI scores were
      positively correlated with the CTP and MELD scores. The mean ALBI score and the
      frequency of grade 3 disease were higher in HBV-ACLF patients than in patients
      with HBV-LC or HBV-HCC. A later HBV-ACLF stage resulted in a higher frequency of
      ALBI grades of 3. In conclusion, ALBI scores exhibited parallel tendencies to the
      CTP and MELD scores in HBV-ACLF, HBV-LC, and HBV-HCC patients; thus, ALBI grading
      may be a simple but applicable method for the evaluation of the functional status
      of patients with HBV-related end-stage liver diseases.

PMID- 29456712
TI  - MicroRNA-144 functions as a tumor suppressor in gastric cancer by targeting
      cyclooxygenase-2.
AB  - Gastric cancer (GC) poses a serious public health threat and the 5-year survival
      rate of patients with GC is low. MicroRNAs (miRNAs/miRs) may serve oncogenic or
      tumor suppressor functions during tumorigenesis by regulating cell proliferation,
      apoptosis, migration and invasion and it has been demonstrated that they may be
      dysregulated in various types of cancer. The present study demonstrated that miR
      144 and GATA4 were downregulated in GC tissues and cell lines and suggested that
      this may be due to hypermethylation. Additionally, miR-144 and GATA4 had
      synergistic effects on GC cells by repressing cell proliferation and inducing
      cell cycle arrest and apoptosis. The results of bioinformatics and a luciferase
      reporter assay indicated that cyclooxygenase-2 (COX-2) is a direct target of miR
      144 and that miR-144 negatively regulated the expression of COX-2, which inhibits
      the viability of GC cells. GATA4 also induced a similar effect on COX-2. Taken
      together, the results of the present study may improve understanding of the
      underlying mechanism of miR-144 and GATA4 in GC.

PMID- 29456713
TI  - In vitro study on the role of SOX9 in trastuzumab resistance of adenocarcinoma of
      the esophagogastric junction.
AB  - Trastuzumab is recommended for the treatment of human epidermal growth factor
      receptor 2-positive adenocarcinoma of the esophagogastric junction (AEG) in
      combination with chemotherapy; however, drug resistance has severely affected its
      clinical application. The present study aimed to investigate the effect of sex
      determining region Y-box 9 (SOX9), a prognostic marker in adjuvant oncological
      settings, on AEG cell proliferation and apoptosis in the presence or absence of
      trastuzumab. Furthermore, the molecular mechanism underlying the role of SOX9 in
      trastuzumab resistance was explored. ESO26 cells were treated with various
      concentrations of trastuzumab, and trastuzumab induced SOX9 expression in a
      concentration-dependent manner, as determined by reverse transcription
      quantitative polymerase chain reaction and western blotting analyses.
      Transfection of ESO26 cells with SOX9 small interfering RNA was conducted to
      knock down SOX9 expression, and the results of MTT and flow cytometry assays
      demonstrated that SOX9 knockdown sensitized ESO26 cells to trastuzumab by
      inhibiting cell proliferation and enhancing cell apoptosis. In addition, it was
      observed that the trastuzumab-induced phosphorylation of AKT was suppressed by
      SOX9 knockdown. In conclusion, the present study demonstrated that SOX9
      participated in trastuzumab resistance by affecting cell proliferation and
      apoptosis, and indicated that SOX9 may exert its effect on trastuzumab resistance
      via activation of the phosphatidylinositol-3-kinase/AKT signaling pathway. This
      study identified a novel mechanism underlying trastuzumab resistance in vitro and
      may be useful in improving the efficacy of trastuzumab treatment.

PMID- 29456714
TI  - FOXK1 promotes glioblastoma proliferation and metastasis through activation of
      Snail transcription.
AB  - Forkhead box K1 (FOXK1) has been identified to have a crucial function in
      development and oncogenesis. However, its role in glioblastoma has remained
      largely elusive and was therefore assessed in the present study. In human
      glioblastoma multiforme (GBM) tissue samples, FOXK1 was determined to be highly
      expressed compared with adjacent normal tissue samples. In addition, high levels
      of FOXK1 were detected in the T98G and LN18 GBM cell lines as compare with those
      in normal human astrocytes. Of note, high expression of FOXK1 was revealed to be
      associated with metastasis and tumor size. Loss- and gain-of-function experiments
      were then performed to determine whether FOXK1 regulates epithelial to
      mesenchymal transition (EMT) and cell proliferation. Knockdown of FOXK1
      significantly suppressed EMT and metastasis of GBM cells, while ectopic
      expression of FOXK1 promoted them. A luciferase reporter assay and a chromatin
      immunoprecipitation assay revealed that FOXK1 activated the transcription of
      Snail. In addition, as the results indicated that FOXK1 promotes GBM cell
      proliferation, the potential effect of FOXK1 on the cell cycle and apoptosis were
      further assessed. While FOXK1 had no effect on apoptosis, it promoted cell
      proliferation via enhancing the S-phase population. In brief, the present study
      indicated that FOXK1 acts as an oncogene with a key function in glioblastoma cell
      proliferation and EMT.

PMID- 29456715
TI  - Protective effect of vitexin reduces sevoflurane-induced neuronal apoptosis
      through HIF-1alpha, VEGF and p38 MAPK signaling pathway in vitro and in newborn
      rats.
AB  - Previous studies have demonstrated that Vitexin possesses antihypertensive, anti
      inflammatory and potential anticancer effects. The present study aimed to
      investigate whether the protective effect of vitexin protects against sevoflurane
      induced neuronal apoptosis and the underlying mechanisms of this protective
      effect. The results demonstrated that Vitexin pretreatment significantly reduced
      neuronal apoptosis, and inhibited caspase-3 activity, apoptosis regulator BAX
      protein expression and malondialdehyde levels in sevoflurane-induced newborn
      rats. In addition, Vitexin pretreatment increased superoxide dismutase and
      glutathione peroxidase activity. Furthermore, it was revealed that treatment with
      vitexin induced hypoxia inducible factor 1alpha subunit (HIF-1alpha) and vascular
      endothelial growth factor (VEGF) protein expression, and suppressed
      phosphorylated-p38 MAP kinase (p38) protein expression in sevoflurane-induced
      newborn rat. Together, the results of the current study suggest that the
      protective effect of vitexin reduces sevoflurane-induced neuronal apoptosis
      through HIF-1alpha-, VEGF- and p38-associated signaling pathways in newborn rats.

PMID- 29456716
TI  - Transient severe motion during arterial phase in patients with Gadoxetic acid
      administration: Can a five hepatic arterial subphases technique mitigate the
      artifact?
AB  - Gadoxetic acid (Gd-EOB-DTPA) is a hepatocyte-specific magnetic resonance (MR)
      contrast agent, which has been increasingly used in recent years. However, it has
      been reported that Gd-EOB-DTPA related transient severe motion (TSM) is sometimes
      observed during the hepatic arterial phase of MR imaging, which may influence
      image quality. Since the hepatic arterial phase of contrast enhancement is used
      for the diagnosis of hepatocellular carcinoma, it is crucial to obtain a decent
      arterial phase imaging. The present study analyzed motion in patients receiving
      Gd-EOB-DTPA, comparing a single arterial phase acquisition to a five arterial
      phase acquisition to determine whether the multiphase acquisition was able to
      alleviate the TSM-related hepatic arterial MR imaging artifact. It was
      demonstrated that the single-phase acquisition failed to provide adequate
      diagnostic image quality in patients with TSM, whereas the multiphase arterial
      acquisition provided acceptable image quality in 20/22 (90.9%) patients with TSM.
      In conclusion, the results of the present study demonstrated that multiphase
      arterial acquisition is superior to single-phase arterial acquisition, mitigating
      arterial MR imaging artifacts caused by TSM after the administration of Gd-EOB
      DTPA.

PMID- 29456717
TI  - Naringin ameliorates endothelial dysfunction in fructose-fed rats.
AB  - High fructose consumption is associated with metabolic disorders including
      hyperglycemia and dyslipidemia, in addition to endothelial dysfunction. Naringin,
      a flavonoid present in citrus fruit, has been reported to exhibit lipid lowering,
      antioxidant, and cardiovascular protective properties. Therefore, the present
      study investigated the effect of naringin on fructose-induced endothelial
      dysfunction in rats and its underlying mechanisms. Male Sprague-Dawley rats were
      given 10% fructose in drinking water for 12 weeks, whereas control rats were fed
      drinking water alone. Naringin (100 mg/kg) was orally administered to fructose
      fed rats during the last 4 weeks of the study. Following 12 weeks, blood samples
      were collected for measurement of blood glucose, serum lipid profile and total
      nitrate/nitrite (NOx). Vascular function was assessed by isometric tension
      recording. Aortic expression of endothelial nitric oxide synthase (eNOS),
      phosphorylated eNOS (p-eNOS), and nitrotyrosine were evaluated by western blot
      analysis. Fructose feeding induced increased levels of blood glucose, total
      cholesterol, triglyceride, and low density lipoprotein. In rat aortae, fructose
      reduced acethycholine-induced vasorelaxation, without affecting sodium
      nitroprusside-induced vasorelaxation. Treatment of fructose-fed rats with
      naringin restored fructose-induced metabolic alterations and endothelial
      dysfunction. Fructose-fed rats also exhibited decreased serum NOx level, reduced
      eNOS and p-eNOS protein expression, and enhanced nitrotyrosine expression in
      aortae. These alterations were improved by naringin treatment. The results of the
      present study suggested that naringin treatment preserves endothelium-dependent
      relaxation in aortae from fructose fed rats. This effect is primarily mediated
      through an enhanced NO bioavailability via increased eNOS activity and decreased
      NO inactivated to peroxynitrite in aortae.

PMID- 29456719
TI  - Estrogen receptor-alpha promoter methylation is a biomarker for outcome
      prediction of cisplatin resistance in triple-negative breast cancer.
AB  - A number of previous studies have indicated the presence of a link between
      estrogen receptor-alpha (ERalpha) methylation and triple-negative breast cancer
      (TNBC). However, the association between ERalpha methylation and drug resistance
      during the treatment of TNBC remains unclear. Methylation-specific polymerase
      chain reaction was used to investigate the methylation of ERalpha in the genomic
      DNA of 35 patients with TNBC who were defined as cisplatin-based chemotherapy
      resistant using chemosensitivity testing. Survival probabilities by covariates
      were assessed using Kaplan-Meier estimator survival analysis and Cox's
      proportional hazards models, adjusting for age, menopausal status, tumor size,
      lymph node metastasis and ERalpha promoter DNA methylation. Of the 35 patients
      with TNBC analyzed, 8 exhibited ERalpha promoter DNA methylation. Cisplatin
      resistance was confirmed to be overwhelmingly associated with ERalpha methylation
      by univariate and multivariate analysis. Even in a limited analysis in patients
      with ERalpha methylation, the results generated from methylated tumor tissue and
      unmethylated tumor tissue revealed that expression of breast cancer type 1/2
      susceptibility proteins was increased in ERalpha-methylated breast tumor tissue
      compared with in unmethylated tissue. The ERalpha methylation group tended to
      have significantly shorter progression-free (P=0.010) and overall (P=0.023)
      survival times compared with those in the unmethylated group. Similarly, shorter
      progression-free (P=0.024) and overall (P=0.018) survival times were observed in
      the cisplatin-resistant group compared with the cisplatin-non-resistant group.
      ERalpha methylation predicts a poor clinical outcome for patients with TNBC. The
      results of the present study indicated that ERalpha methylation may be a
      candidate surrogate biomarker for outcome prediction and cisplatin resistance in
      TNBC. Further investigation is required to identify potential biomarkers in a
      larger cohort in a prospective study.

PMID- 29456718
TI  - Molecular challenges of neuroendocrine tumors.
AB  - Neuroendocrine tumors (NETs) are a very heterogeneous group that are thought to
      originate from the cells of the endocrine and nervous systems. These tumors
      develop in a number of organs, predominantly in the gastrointestinal and
      pulmonary systems. Clinical detection and diagnosis are reliable at the late
      stages when metastatic spread has occurred. However, traditional conventional
      therapies such as radiation and chemotherapy are not effective. In the majority
      of cases even surgical resection at that stage is unlikely to produce promising
      reusults. NETs present a serious clinical challenge, as the survival rates remain
      low, and as these rare tumors are very difficult to study, novel approaches and
      therapies are required. This review will highlight the important points of
      accumulated knowledge covering the molecular aspects of the role of
      neuroendocrine cells, hormonal peptides, the reasons for ectopic hormone
      production in NET, neuropeptides and epigenetic regulation as well as the other
      challenging questions that require further understanding.

PMID- 29456720
TI  - miR-494 inhibits cervical cancer cell proliferation through upregulation of SOCS6
      expression.
AB  - It is unclear how microRNA (miR)-494 inhibits the proliferation of cervical
      cancer cells by altering the expression of SOCS6. Therefore, the present study
      aimed to investigate the molecular mechanism underlying miR-494 regulation of
      suppressor of cytokine signaling 6 (SOCS6) in human cervical cancer samples and
      the human cervical cancer HeLa cell line. The expression of miR-494 was
      determined using reverse transcription-quantitative polymerase chain reaction. In
      addition, TargetScan was used to predict miR-494 target genes and the luciferase
      reporter assay was used to determine whether SOCS6 was a direct target of miR
      494. The results of the present study demonstrated that compared with the
      cervical intraepithelial neoplasia and normal cervical tissues, the miR-494
      expression level in cervical cancer samples was significantly decreased (P<0.01).
      In addition, compared with normal cervical tissue, miR-494 expression level was
      significantly decreased in cervical intraepithelial lesions (P<0.05).
      Furthermore, the expression of miR-494 was associated with patients with or
      without lymph node metastasis, clinical stage and depth of stromal invasion
      (P<0.01); however, miR-494 expression was not identified to be associated with
      age, tumor size and menopausal status (P>0.05). Transfection of a miR-494 mimic
      significantly increased the expression level of miR-494 in HeLa cells (P<0.01),
      and anti-miR-494 transfection decreased the expression of miR-494 (P<0.01). An
      MTT proliferation assay and Boyden chamber invasion ability assay revealed that
      miR-494 mimic transfection significantly inhibited the proliferation, and
      invasion ability of HeLa cells (P<0.01), whereas anti-miR-494 transfection
      significantly increased the proliferation and invasion ability (P<0.05). SOCS6
      was predicted, using bioinformatics, to be the target gene of miR-494 and this
      was validated using a luciferase reporter assay. Western blot analysis revealed
      that transfection of miR-494 significantly increased the expression of SOCS6 in
      HeLa cells, and transfection of anti-miR-494 significantly decreased the
      expression of SOCS6. Therefore, the results of the present study demonstrated
      that miR-494 expression in cervical cancer was significantly decreased.
      Exhibiting a decreased expression level of miR-494 may result in enhanced
      proliferative and invasive abilities of HeLa cell, thus contributing to the
      occurrence, and development of cervical cancer.

PMID- 29456721
TI  - Combined treatment with D-allose, docetaxel and radiation inhibits the tumor
      growth in an in vivo model of head and neck cancer.
AB  - The present study was designed to evaluate the effect of one rare sugar, D
      allose, on normal human cells and cutaneous tissue, and to investigate the
      radiosensitizing and chemosensitizing potential of D-allose in an in vivo model
      of head and neck cancer. Results indicated that D-allose did not inhibit the
      growth of normal human fibroblasts TIG-1 cells, and no apoptotic changes were
      observed after D-allose and D-glucose treatment. The mRNA expression levels of
      thioredoxin interacting protein (TXNIP) in TIG-1 cells after D-allose treatment
      increased by 2-fold (50.4 to 106.5). Conversely, the mRNA expression levels of
      TXNIP in HSC3 cancer cells increased by 74-fold (1.5 to 110.6), and the
      thioredoxin (TRX)/TXNIP ratio was markedly reduced from 61.7 to 1.4 following D
      allose treatment. Combined multiple treatments with docetaxel, radiation and D
      allose resulted in the greatest antitumor response in the in vivo model.
      Hyperkeratosis, epidermal thickening and tumor necrosis factor-alpha
      immunostaining were observed following irradiation treatment, but these
      pathophysiological reactions were reduced following D-allose administration.
      Thus, the present findings suggest that D-allose may enhance the antitumor
      effects of chemoradiotherapy whilst sparing normal tissues.

PMID- 29456722
TI  - Fucosterol exhibits selective antitumor anticancer activity against HeLa human
      cervical cell line by inducing mitochondrial mediated apoptosis, cell cycle
      migration inhibition and downregulation of m-TOR/PI3K/Akt signalling pathway.
AB  - Cervical cancer greatly contributes to cancer-associated mortalities worldwide.
      The growing incidence of cervical cancer is of primary concern, and has signaled
      the need for multiple treatment options. Despite preliminary responses to
      chemotherapy and/or surgical interventions, the tumors consistently relapse.
      Previously, natural products gained attention for their diverse bioactivities,
      which include however are not limited to, neuroprotective, antimicrobial and
      anticancer effects. The present study evaluated the anticancer activity of
      fucosterol against a panel of human cancer cell lines. Results indicated that
      fucosterol exhibited selective inhibitory activity against human HeLa cervical
      cancer cell line with an IC50 of 40 uM. Fucosterol also induced apoptosis in HeLa
      cells and prompted reactive oxygen species mediated alterations in mitochondrial
      membrane potential. It triggered cell cycle arrest of HeLa cells at G2/M check
      point and exerted inhibitory effects on cell migration. The activation of the
      phosphoinositide-3-kinase (PI3K)/AKT Serine/Threonine Kinase 1 (AKT)/mechanistic
      target of Rapamycin (mTOR) pathway is important in cancer tumorigenesis,
      progression and chemotherapy resistance. The results demonstrated that fucosterol
      significantly inhibited the expression levels of key proteins of the
      PI3K/Akt/mTOR signaling pathway. Overall, the results of the present study
      suggest that fucosterol may prove beneficial in the management of cervical
      cancer.

PMID- 29456724
TI  - Long noncoding RNA BLACAT1 promotes cell proliferation and invasion in human
      cervical cancer.
AB  - Cervical cancer is one of the leading causes of mortality in females worldwide.
      Predisposition to distant metastasis has reduced the prognosis of this
      malignancy, thus the identification of a novel agent for metastatic cervical
      cancer is required. Long noncoding RNAs (LncRNAs) have been reported to serve
      significant roles in human tumorigenesis. The present study aimed to investigate
      the effects of a newly discovered LncRNA bladder cancer associated transcript 1
      (non-protein coding) (BLACAT1) on cell proliferation and metastasis in cervical
      cancer. A total of 100 patients with cervical cancer were included, and tumor
      tissues as well as the adjacent non-cancerous counterparts were collected for
      reverse transcription-quantitative polymerase chain reaction analysis. It was
      demonstrated that BLACAT1 was highly expressed in human cervical cancer tissues
      and cell lines. The knockdown of BLACAT1 with specific short hairpin RNA reduced
      colony formation rates in ME180 and C33A cells. Cell cycle and cell proliferation
      assays revealed that depletion of BLACAT1 in ME180, and C33A cells arrested the
      cell cycle at the G0/G1 phase and inhibited cell proliferation. Transwell assays
      demonstrated that the knockdown of BLACAT1 inhibited cell migration and invasion
      in ME180, and C33A cells. Moreover, wound-healing assays supported the
      aformentioned observations. Western blot analysis showed that the knockdown of
      BLACAT1 in ME180 and C33A cells decreased the protein levels of cyclin B1, cell
      division cycle 25C, and N-cadherin, while increasing the protein level of E
      cadherin. These findings indicated the oncogenic potential of BLACAT1 in cervical
      cancer, which may provide novel insights for the clinical diagnosis and treatment
      of cervical cancer.

PMID- 29456723
TI  - miR-96 promotes breast cancer metastasis by suppressing MTSS1.
AB  - Novel, non-invasive biomarkers with high sensitivity and specificity are critical
      for breast cancer treatment, and prognosis. MicroRNA (miR)-96 has been
      demonstrated to be highly expressed in several solid malignancies, including
      breast cancer. However, its expression and function in the metastasis and
      prognosis of breast cancer have not been fully explored, and its regulation
      mechanisms remain unclear. In the present study, the serum miR-96 expression in
      healthy controls, benign and malignant breast cancer types was compared by using
      reverse transcription-quantitative polymerase chain reaction. The effect of
      chemotherapy on miR-96 expression in breast cancer was also investigated. Result
      revealed that miR-96 expression was increased in malignant breast cancer types
      and reduced in patients following chemotherapy treatment. The effect of miR-96
      manipulation on the migration of breast cancer cells was also investigated by
      using wound healing, and Transwell migration assays. These results revealed that
      the induced expression of miR96 led to enhanced wound closing and trans-membrane
      cell numbers. By using bioinformatics analysis, western blotting and
      immunohistochemical staining, the metastasis suppressor-1 (MTSS1) gene was
      identified to be the functional target of miR-96 in the promotion of cell
      migration. In conclusion, it was identified that miR-96 exhibited an increased
      level in serum samples of patients with malignant breast cancer in comparison
      with benign breast tumor types and health controls and may be substantially
      reduced by chemotherapy treatment, implying that it may be used as a prognostic
      marker in breast cancer. miR-96 overexpression may inhibit migration of breast
      cancer cells by downregulating MTSS1 expression.

PMID- 29456725
TI  - Application of deep learning to the classification of images from colposcopy.
AB  - The objective of the present study was to investigate whether deep learning could
      be applied successfully to the classification of images from colposcopy. For this
      purpose, a total of 158 patients who underwent conization were enrolled, and
      medical records and data from the gynecological oncology database were
      retrospectively reviewed. Deep learning was performed with the Keras neural
      network and TensorFlow libraries. Using preoperative images from colposcopy as
      the input data and deep learning technology, the patients were classified into
      three groups [severe dysplasia, carcinoma in situ (CIS) and invasive cancer
      (IC)]. A total of 485 images were obtained for the analysis, of which 142 images
      were of severe dysplasia (2.9 images/patient), 257 were of CIS (3.3
      images/patient), and 86 were of IC (4.1 images/patient). Of these, 233 images
      were captured with a green filter, and the remaining 252 were captured without a
      green filter. Following the application of L2 regularization, L1 regularization,
      dropout and data augmentation, the accuracy of the validation dataset was ~50%.
      Although the present study is preliminary, the results indicated that deep
      learning may be applied to classify colposcopy images.

PMID- 29456726
TI  - Association of histone deacetylase expression with histology and prognosis of
      ovarian cancer.
AB  - Histone deacetylase (HDAC) inhibitor is known to have a cytotoxic effect on
      ovarian cancer cell lines. The present study analyzed the association between
      immunohistochemical HDAC expression and clinicopathological findings, in
      particular, the association with histological type and effect of chemotherapy.
      The histology of the 201 ovarian cancers addressed was as follows: Serous
      carcinoma (SEC), 100 cases; clear cell carcinoma (CCC), 56 cases; endometrioid
      carcinoma (EMC), 36 cases; and mucinous carcinoma (MUC), 9 cases.
      Immunohistochemical analyses of HDACs 1, 2, 3, 4, 5, 6 and 7 expression levels
      were performed using tissue microarrays, composed of 201 primary tumors and 38
      tumors following chemotherapy. Overexpression of HDAC1 was detected in the
      nucleus of all cases with MUC, followed by CCC (80%), SEC (73%), and EMC (53%).
      CCC specifically demonstrated HDAC7 expression in both the nucleus (27%) and the
      cytoplasm (54%), and HDAC6 expression in the nucleus (34%). The comparison
      between prior to and following chemotherapy revealed a nuclear expression
      increase in HDAC1 (76% vs. 92%; P=0.03) and HDAC7 (0.0 vs. 16%; P=0.01), and
      cytoplasmic expression increase in HDAC6 (40 vs. 74%; P=<0.01) and HDAC7 (16 vs.
      66%; P=<0.01). HDAC1 nuclear expression adversely affected overall survival in
      SEC (P=0.02) and EMC (P=0.03), and HDAC7 cytoplasmic expression in CCC was
      associated with a poor prognosis (P=0.06). In multivariate analysis, HDAC6
      nuclear expression was determined as a poor prognostic factor (hazard ratio=3.51;
      95% confidence interval, 1.49 to 8.27, P=<0.01). In the subgroup analysis, HDAC6
      nuclear expression was associated with a poor prognosis in CCC (P=0.07),
      International Federation of Obstetrics and Gynecology stage III/IV (P=0.07), and
      suboptimal surgery (P=<0.01). In conclusion, HDACs may be associated with the
      prognosis of ovarian cancers, depending on the histological subtypes, and
      upregulated following chemotherapy. HDAC1, 6 and 7 may therefor act as promising
      therapeutic targets in the future.

PMID- 29456727
TI  - Risk factors and coping strategies of severe community-acquired pneumonia in
      chemotherapy induction period of acute leukemia.
AB  - The risk factors and coping strategies of severe community-acquired pneumonia
      (SCAP) in chemotherapy induction period of acute leukemia were investigated.
      Eighty-six patients with CAP in chemotherapy induction period of acute leukemia
      in Dezhou Hospital from March 2014 to February 2017 were selected and divided
      into observation group (SCAP group, n=45) and control group (non-SCAP group,
      n=41) according to the acute physiology and chronic health evolution II (APACHE
      II) score. The blood, sputum, nasopharyngeal secretion and pleural effusion
      samples were collected from patients in both groups, and the samples were
      detected for pathogens, followed by the analysis of relevant factors. The dynamic
      changes in the sequential organ failure assessment (SOFA) score, procalcitonin
      (PCT), D-dimer (D-D) and C-reactive protein (CRP) levels in patients were
      observed before and after the corresponding treatment strategies were taken. The
      total distribution ratio of pathogens from high to low in the two groups was as
      follows: bacterium, virus, fungus, mycoplasma and chlamydia trachomatis; there
      was no significant difference between the two groups (P>0.05). Logistic
      regression analysis showed that the repeated infection (OR=3.315, P=0.005), multi
      resistant bacterial infection (OR=1.915, P=0.008) and D-D (OR=1.936, P=0.009)
      were independent risk factors for SCAP (P<0.05). After different coping
      strategies were taken, the SOFA score, PCT, D-D and CRP levels in the two groups
      were significantly decreased, and they were obviously higher in observation group
      than those in control group (P<0.05). Repeated infection, D-D level and multi
      resistant bacterial infection are the risk factors affecting the SCAP in
      chemotherapy induction period of acute leukemia. The coping strategies can
      effectively relieve the patient's condition, reduce the severity of disease and
      improve the survival rate of patients.

PMID- 29456728
TI  - Values of miR-34a and miR-218 expression in the diagnosis of cervical cancer and
      the prediction of prognosis.
AB  - The expression levels of microribonucleic acid 34a (miR-34a) and miR-218 in the
      serum and tumor tissues of patients with cervical cancer were investigated to
      explore their relationship with the diagnosis of cervical cancer. Fifty patients
      with cervical cancer were selected, and 30 normal patients were selected as the
      control group. The expression levels of miR-34a and miR-218 were detected by
      quantitative real-time polymerase chain reaction. The relationship between the
      expression of miR-34a and miR-218 was analyzed using Pearson's correlation
      coefficient, and the receiver operating characteristic (ROC) curve was plotted
      for the analysis of values of the expression of miR-34a and miR-218. The
      correlation of the expressions of miR-34a and miR-218 in the serum with
      pathological parameters and the prognosis was analyzed. The expression levels of
      miR-34a and miR-218 in cervical cancer patients were significantly lower than
      those in normal patients. The ROC curve showed the area under curve (AUC) of miR
      34a was 0.893, and miR-218 was 0.794. The low expression of miR-34a in patients
      with cervical cancer was correlated with the degree of tumor differentiation,
      lymph node metastasis and the International Federation of Gynecology and
      Obstetrics staging. The low expression of miR-218 was related to the degree of
      differentiation as well as invasion and metastasis. The 5-year overall survival
      rate of patients was 66%, and the low expression of miR-34a and miR-218 indicated
      a worse survival prognosis. The low expression of miR-34a in patients with
      cervical cancer is related to the degree of tumor differentiation as well as
      invasion and metastasis, and the low expression of miR-218 is related to the
      degree of tumor differentiation, invasion and metastasis and clinical staging.
      miR-34a and miR-218 in the serum can be used as markers for the diagnosis of
      cervical cancer and reference indicators for the evaluation of prognosis.

PMID- 29456729
TI  - Expression of matrix metalloproteinase-7 correlates with the invasion of T1
      colorectal carcinoma.
AB  - T1 colorectal carcinomas (CRCs) are an initial site of metastatic spread. Various
      risk factors for lymph node metastasis have been investigated in T1 CRCs.
      However, the major step in the entire process of metastasis remains unclear. In
      terms of carcinoma invasion and metastasis, matrix metalloproteinases (MMPs) have
      recently gained increasing attention. Notably, MMP-7 is frequently overexpressed
      in CRCs, but its implication has not been determined in T1 CRCs yet. The present
      study aimed to clarify the associations between the pathological risk factors of
      T1 CRCs and MMP-7. In the current study, 211 lesions of T1 CRC that were resected
      endoscopically or surgically at Showa University Northern Yokohama Hospital
      (Yokohama, Japan) between April 2008 and December 2009 were retrospectively
      analyzed. MMP-7 was immunostained and evaluated by its frequency of expression.
      Pathological factors of T1 CRCs were analyzed in association with MMP-7
      expression. Furthermore, the ultrastructural alterations of carcinoma invasion
      were examined using low vacuum-scanning electron microscopy (LV-SEM). MMP-7
      expression was associated with venous invasion (P=0.005), and LV-SEM revealed the
      disappearance of the normal structure of collagen and elastic fibers of veins
      invaded by tumor cells expressing MMP-7. At the invasive front, MMP-7 has a vital
      role in carcinoma invasion, correlating with venous invasion of T1 CRCs.

PMID- 29456730
TI  - The regulation and function of microRNA-377/RASSF8 signaling axis in gastric
      cancer.
AB  - Gastric cancer is a major cause of cancer-associated mortality worldwide. The
      aberrant expression of microRNA (miRNA) is involved in tumorigenesis. Ras
      proteins transfer information from the extracellular environment to internal
      cellular compartments and are essential in numerous signal transduction pathways.
      To investigate the regulation, function and clinical significance of the
      miRNA377/Ras association domain family (RASSF) 8 signaling axis in gastric
      cancer, reverse transcription-quantitative polymerase chain reaction,
      immunohistochemistry, cell counting kit-8, western blotting, and Transwell assays
      were used. The results revealed that expression of RASSF8 was significantly
      upregulated in normal gastric tissues compared with gastric cancer, which was
      further confirmed by immunohistochemical analysis, and its expression level was
      increased in normal gastric cells compared with gastric cancer cell lines.
      However, the expression of miR-377 was significantly upregulated in gastric
      cancer compared with normal gastric tissues. In addition, RASSF8 overexpression
      in BGC-823 gastric cancer cells significantly inhibited the proliferation,
      apoptosis and invasive abilities of cells. Whereas miR-377 attenuated these
      effects due to downregulated RASSF8 expression by directly targeting its 3'
      untranslated region. Furthermore, in the current study, miR-377 was not able to
      reverse the effects of RASSF8 overexpression on gastric cancer cells.
      Collectively, the RASSF8 gene may represent a novel molecular target involved in
      gastric cancer development and may be useful in targeted therapy of patients with
      gastric cancer.

PMID- 29456731
TI  - Analysis of middle- and long-term efficacy of thoracoscope-assisted segmental
      resection of the lung on non-small cell lung cancer in the early stage.
AB  - We investigated the short- and long-term efficacy of thoracoscope-assisted
      segmental resection of lung of non-small cell lung cancer (NSCLC). We selected a
      total of 94 patients with lung cancer in the early stage who were admitted to The
      First People's Hospital of Xuzhou for treatment between March 2011 and February
      2012. Patients were divided randomly into either the control group (n=47) or the
      observation group (n=47). In the observation group, patients received
      thoracoscope-assisted segmental resection of lung, while in the control group,
      the conventional thoracic surgery was performed for treatment. After surgeries,
      we observed the incidence rate of complications among the two groups, and enzyme
      linked immunosorbent assay (ELISA) was adopted to detect levels of inflammatory
      factors. We also compared the cardiac and pulmonary functions, the levels of
      immunoglobulins and subgroups of T lymphocytes in the peripheral blood of the
      patients. In addition, all patients attended a 5-year follow-up to determine the
      recurrence and survival rate. Compared to the control group, patients in the
      observation group had significantly less intra-operative bleeding volume, a
      shorter duration of surgery, and suffered slighter pain after surgery (P<0.05).
      After surgery, the incidence rate of complications in the observation group was
      significantly lower than that in the control group (P<0.05). After surgeries,
      patients in both groups experienced a remarkable improvement in cardiac and
      pulmonary functions, and the improvement in the observation group was superior to
      that of the control group (P<0.05). During the 5-year follow-up, the survival
      rate of the observation group is significantly higher than that in thecontrol
      group, and patients in the observation group experienced a lower recurrence rate
      than those in the control group (P<0.05). Thus, thoracoscope-assisted segmental
      resection of lung is of great significance in clinical practice.

PMID- 29456732
TI  - Two protein-coding genes act as a novel clinical signature to predict prognosis
      in patients with ovarian serous cystadenocarcinoma.
AB  - Ovarian cancer is the seventh most common type of cancer and the eighth most
      common cause of cancer-associated mortality among women. A number of studies have
      hypothesized that the expression status of certain genes may be used to predict
      prognosis in ovarian cancer. In the present study, the RNA expression data from
      next-generation sequencing and the clinical information of 413 patients from The
      Cancer Genome Atlas dataset was downloaded to identify the association between
      gene-expression level and the survival time of the patients with ovarian serous
      cystadenocarcinoma. A five-gene model was predicted to be significantly
      associated with patient survival in ovarian serous cystadenocarcinoma by using
      random survival forests variable hunting algorithm and Cox analysis. A total of
      two genes, mesencephalic astrocyte-derived neurotrophic factor and dedicator of
      cytokinesis 11, of the predicted five genes demonstrated positive expression in
      the ovarian serous cystadenocarcinoma cancer tissues by polymerase chain reaction
      analysis. Kaplan-Meier and Receiver Operating Characteristic analysis confirmed
      that the model of the two genes exhibited high sensitivity and specificity to
      predict the prognostic survival of patients. In conclusion, the expression of the
      two genes in the two-gene model was associated with the prognostic outcomes of
      patients with ovarian serous cystadenocarcinoma; the model demonstrated potential
      as a novel prognostic indicator, which may have important clinical significance.

PMID- 29456733
TI  - Fbxw7 regulates renal cell carcinoma migration and invasion via suppression of
      the epithelial-mesenchymal transition.
AB  - F-box and WD repeat domain containing 7 (Fbxw7) is an F-box protein that belongs
      to the SKP1-CUL1-F-box protein E3 ligase complex and is responsible for
      transferring the ubiquitin molecule to the substrate, which results in its
      recognition and subsequent degradation by proteasomes. Furthermore, it can
      identify a network of signaling proteins that function in cell growth, diversion
      and apoptosis. In the present study, Fbxw7 was downregulated in renal cell
      carcinoma (RCC) tissues compared with the adjacent non-tumor tissues and its
      expression was significantly associated with the tumor-node-metastasis stage,
      lymph node metastasis and distant metastasis in patients with RCC. Furthermore,
      multivariate Cox regression analyses indicated that Fbxw7 expression was an
      independent factor for the prediction of the overall survival of patients with
      RCC. A functional study demonstrated that downregulation of Fbxw7 facilitated
      tumor cell migration and invasion via the epithelial-mesenchymal transition
      (EMT). Therefore, the results of the current study indicted that Fbxw7 is an anti
      oncogene that serves a notable function in RCC development by suppressing RCC
      metastasis and the EMT, indicating the potential therapeutic value of Fbxw7 in
      inhibiting metastasis in RCC.

PMID- 29456734
TI  - Homeobox B3 promotes tumor cell proliferation and invasion in glioblastoma.
AB  - Glioblastoma (GBM) is the most aggressive brain tumor in adults with the highest
      mortality rate. Despite advances achieved in treatment and research, the median
      survival for patients with GBM remains <1.5 years. This figure prompted the
      present study to identify novel genes associated with GBM development and
      progression to ultimately improve GBM treatment. The current study sought to
      determine the role of homeobox B3 (HOXB3) in GBM cell invasion and proliferation.
      HOXB3 was highly expressed in GBM tissues and glioma cell lines. To establish in
      vitro cell models for investigation, U87-MG and U251-MG, two typical GBM cells,
      were selected to generate corresponding cells lines that constitutively silenced
      HOXB3 expression using a lentivirus-mediated RNA interference approach. The
      results of the knockdown revealed that glioma cells stably expressing HOXB3 short
      hairpin RNA exhibited significantly decreased proliferation levels when compared
      with untransfected cells. The effect of HOXB3 on glioma cell invasion was also
      examined. Silencing of HOXB3 resulted in a marked reduction in invasiveness.
      Furthermore, HOXB3 silencing led to the upregulation of E-cadherin and
      downregulation of mesenchymal markers, N-cadherin and vimentin. Taken together,
      the findings of the present study indicate that HOXB3 promotes cell proliferation
      and invasion.

PMID- 29456735
TI  - Metadherin contributes to epithelial-mesenchymal transition and paclitaxel
      resistance induced by acidic extracellular pH in nasopharyngeal carcinoma.
AB  - Paclitaxel resistance is a challenge to the treatment of nasopharyngeal carcinoma
      (NPC). An acidic extracellular pH (pHe), a hallmark of solid tumors, is
      demonstrated to decrease the efficacy of chemotherapy. However, the precise
      function of acidic pHe in mediating chemotherapy in NPC remains unknown. In the
      present study, acidic pHe significantly decreased the cytotoxicity of paclitaxel
      in NPC cells. In addition, epithelial-mesenchymal transition (EMT)-like changes
      were observed in NPC cells cultured at acidic pHe. Metadherin (MTDH), a novel
      oncogene, is expressed in multiple types of solid tumor, and is associated with
      several malignant cell characteristics, including malignant cell transformation,
      proliferation, angiogenesis, chemoresistance, invasion and metastasis. In the
      present study, MTDH expression was increased in NPC cells that had been cultured
      at an acidic pHe. Furthermore, the silencing of MTDH expression reversed EMT
      molecular marker expression and sensitized NPC cells to paclitaxel. Taken
      together, the results of the present study provide evidence to support an
      association between acidic pHe-induced paclitaxel resistance and MTDH-mediated
      EMT in NPC cells. Thus, targeting MTDH may provide a novel strategy for
      overcoming chemoresistance in NPC therapy.

PMID- 29456736
TI  - Brucea javanica seed oil enhances the radiosensitivity of esophageal cancer by
      inhibiting hypoxia-inducible factor 1alpha, in vitro and in vivo.
AB  - Brucea javanica oil emulsion (BJOE) has been used clinically to treat esophageal
      cancer combined with radiotherapy for numerous years in China. However, the
      detailed mechanism remains unclear. Thus, the effects of BJOE on the
      radiosensitivity of esophageal squamous cell carcinoma (ESCC) were evaluated in
      vitro and in vivo. The growth inhibitory effects of different BJOE concentrations
      were determined through an MTT assay. Radiosensitivity was evaluated through
      focal formation measurements and clone formation assays. The effects of BJOE on
      radiation-induced apoptosis were examined through flow cytometric analysis. The
      effects of BJOE on hypoxia-inducible factor 1alpha (HIF-1alpha) protein levels in
      vitro and in vivo were respectively analyzed through western blot analyses and
      enzyme-linked immunosorbent assays. BJOE significantly inhibited ECA109 cell
      proliferation in a dose- and time-dependent manner. Pretreatment with 2.5 mg/ml
      BJOE increased ECA109 radiosensitivity. BJOE in combination with radiation
      increased the DNA double-strand breaks. Compared with radiation alone, BJOE and
      radiation significantly increased the apoptotic rate of ECA109 cells. BJOE also
      decreased the HIF-1alpha protein levels in vitro and in vivo. The results from
      the present study demonstrated that BJOE enhanced the radiosensitivity of human
      ESCC. This finding was associated with the inhibition of HIF-1alpha expression.
      Therefore, BJOE may be a potential radiotherapy sensitization drug due to its
      significant anti-hypoxic activity.

PMID- 29456737
TI  - Distinctive profiles of tumor-infiltrating immune cells and association with
      intensity of infiltration in colorectal cancer.
AB  - Tumor-infiltrating immune cells are heterogeneous and consist of characteristic
      compartments, including T helper (Th)1 and regulatory T (Treg) cells that exhibit
      distinctive biological functions. The present study investigated the profile of
      infiltrating immune cells from surgically removed tumor tissues from patients
      with colorectal cancer. The characteristic transcription factors of Th1 and Th2
      cells, Treg cells, Th17 cells and T follicular helper (Tfh) cells were analyzed.
      The results demonstrated that a marked increased number of Treg cells presented
      in tumor infiltrates when compared with non-tumor adjacent tissues. An increased
      number of Th1 and Tfh cells existed in tumor infiltrates compared with non
      tumorous adjacent tissues, while the infiltration of Th17 and Th2 cells was
      similar between tumor and non-tumor adjacent tissues. Furthermore, there were an
      increased number of Treg cells in tumors with low infiltration compared with
      those with high infiltration. The expression of CXC motif chemokine (CXC)
      receptor 3, CXC ligand (CXCL)L9 and CXCL10 was significantly increased on
      infiltrating T cells in tumors with high infiltration as compared with those with
      low infiltration. Macrophages exhibited a dominant M2 phenotype in tumor
      infiltrates of colorectal cancer, whereas a balanced M1 and M2 phenotype
      presented in macrophages from the peripheral blood. In vitro stimulation of
      macrophages isolated from tumor tissue of colorectal cancer with granulocyte
      macrophage colony-stimulating factor and lipopolysaccharide did not drive to an
      inflammatory phenotype. The results provide insights into the pattern of immune
      cell infiltration in Chinese patients with colorectal cancer. It may be
      beneficial that patients with colorectal cancer are screened for the defined
      profile along with the expression of CXCL9 and CXCL10 in order to achieve better
      efficacy in clinical applications of immune-based therapy, including anti
      programmed cell death protein 1 therapy.

PMID- 29456738
TI  - Recurrence of adenoid cystic carcinoma of the trachea treated with radical
      radiotherapy: A case report.
AB  - Adenoid cystic carcinoma (ACC) of the trachea is a relatively rare tumor among
      thoracic diseases. The present study reports the case of a 23-year-old woman with
      ACC of the trachea who underwent surgical resection of the tumor in The National
      Institute of Tuberculosis and Lung Diseases (Warsaw, Poland). Histopathological
      examination revealed that the tumor was not completely resected (R2 resection)
      and strict observation of the patient was therefore prescribed. After ~9 years of
      follow-up, clinical and histopathological tumor progression was confirmed and the
      patient was referred to the Centre of Oncology in Warsaw. The localization and
      advanced nature of the disease precluded surgical intervention, and radical
      radiotherapy was therefore performed using intensity-modulated radiation therapy.
      A total dose of 7,590 Gy, the planning target volume, was administered. A
      hyperfractionation scheme of radiotherapy was used: 2 fractions of 1.15 Gy daily,
      with at least a 6 h break in between. Tumor regression was observed following
      treatment and has been maintained for >3 years, assessed by clinical and computed
      tomography and positron emission tomography imaging examinations.

PMID- 29456739
TI  - Effects of PHA-665752 and vemurafenib combination treatment on in vitro and
      murine xenograft growth of human colorectal cancer cells with BRAFV600E
      mutations.
AB  - It remains unknown whether blockade of B-Raf proto-oncogene, serine/threonine
      kinase (BRAF)V600E signaling and MET proto-oncogene, receptor tyrosine kinase (c
      Met) signaling is effective in suppressing the growth of human colorectal cancer
      (CRC) cells. The present study investigated the effects of the vemurafenib alone
      and in combination with c-Met inhibitor PHA-665752 on the growth of human CRC
      cells in vitro and in mouse xenografts. HT-29 and RKO CRC cell lines with
      BRAFV600E mutations and mice bearing HT-29 xenografts were treated with
      vemurafenib in the absence or presence of PHA-665752. Cell viability and cycle
      phase were respectively examined by using the MTT and flow cytometry assay.
      Immunohistochemistry was conducted to detect the protein expression levels of
      hepatocyte growth factor (HGF), phosphorylated (p)-c-Met, p-AKT serine/threonine
      kinase (AKT) and p-extracellular signal-regulated kinase (p-ERK). The MTT assay
      demonstrated that the growth of RKO and HT-29 cells was inhibited by PHA-665752
      in a time- and dose-dependent manner (P<0.05), however no significant suppressive
      effects were observed with vemurafenib. Relative to the PHA-665752 or vemurafenib
      stand-alone treatment groups, the combination of PHA-665752 and vemurafenib had a
      significant inhibitory effect on the proliferation of CRC cell lines (P<0.05).
      The mean tumor volume in mice treated with vemurafenib in combination with PHA
      665752 was significantly smaller compared with those treated with only
      vemurafenib or PHA-665752 (P<0.05). Flow cytometry assay revealed that the G0/G1
      phase frequency was significantly increased in the combination group compared
      with any other treatment groups (P<0.05). Immunohistochemistry demonstrated that
      vemurafenib in combination with PHA-665752 effectively induced the expression of
      p-c-Met, p-AKT and p-ERK, however had no effect on HGF.

PMID- 29456740
TI  - An obligatory anaerobic Salmonella typhimurium strain redirects M2 macrophages to
      the M1 phenotype.
AB  - A genetically engineered Salmonella typhimurium strain that may be applied in the
      medically useful therapeutic strategy of using bacterial agents to target breast
      cancer in a tumor-bearing nude mouse model has been previously reported.
      Furthermore, immune cell accumulation in breast tumor types has been observed,
      particularly distributed in regions surrounding the bacteria. M2 macrophages are
      associated with breast cancer aggressiveness, whereas M1 macrophages are prone to
      devouring bacteria and killing cancer cells. Therefore, this engineered tumor
      targeting salmonella strain was used in an attempt to reverse the phenotype of M2
      macrophages into the M1 phenotype. Subsequent to the co-culture of M2 macrophages
      with the bacteria for a short time, >50% of the M2 macrophages were invaded by
      bacteria. These M2 macrophages exhibited a decreased expression of mannose
      receptor (an M2 phenotypic marker) and increased expression of human leukocyte
      antigen-antigen D related (an M1 phenotypic marker). The results of the present
      study indicated that differentiated M2 macrophages may be redirected into the M1
      phenotype following exposure to the engineered bacteria stimulus. This effect may
      be a potential mechanism by which bacteria retard tumor growth. Thus, this
      engineered bacterium may be a useful candidate for targeting and redirecting M2
      macrophages into the M1 phenotype.

PMID- 29456741
TI  - Overexpression of flavin-containing monooxygenase 5 predicts poor prognosis in
      patients with colorectal cancer.
AB  - The present study investigated the expression and clinical significance of flavin
      containing monooxygenase 5 (FMO5) in colorectal cancer (CRC). The expression of
      FMO5 was detected by immunohistochemistry in 208 colon cancer tissues and 8
      normal colon tissues. Then, the correlations of FMO5 expression with several
      clinicopathological features were evaluated. FMO5 mRNA expression from The Cancer
      Genome Atlas dataset was assessed for further validation. In addition, the
      association of the expression of FMO5 with prognosis was further evaluated by
      Kaplan-Meier survival curves and Cox proportional hazards model. The FMO5 protein
      level in colon cancer tissues was significantly higher than that in normal colon
      tissues (P<0.001). Overexpression of FMO5 was associated with an advanced
      clinical stage of cancer (P=0.018) and lymph node metastasis (P=0.03). The TCGA
      dataset also demonstrated that FMO5 was upregulated in CRC with advanced clinical
      stage (P=0.047), lymph node metastasis (P=0.045) and distant metastasis
      (P=0.030). The Kaplan-Meier survival curves showed that higher FMO5 mRNA
      indicated a shorter overall survival in patients with CRC compared with a low
      expression of FMO5 (P=0.029). Cox proportional hazards regression revealed that a
      high FMO5 mRNA level served as an independent prognostic factor for patients with
      CRC (hazard ratio, 2.865; 95% confidence interval, 1.116-7.355; P=0.029). A high
      expression of FMO5 may serve roles in colorectal carcinogenesis and distant
      metastasis. FMO5 may be an independent predictive factor for the prognosis of
      CRC.

PMID- 29456742
TI  - miR302a inhibits the proliferation of esophageal cancer cells through the MAPK
      and PI3K/Akt signaling pathways.
AB  - MicroRNAs (miRNAs/miRs) are involved in the regulation of various types of
      cancer, either as oncogenes or tumor suppressors. miR302a has been reported that
      it could suppress tumor cell proliferation by inhibiting Akt in prostate cancer.
      The present study examined the effect of miR302a on proliferation and invasion in
      esophageal cancer cell lines. The expression levels of miR302a in esophageal
      cancer cell lines was determined by reverse transcription-polymerase chain
      reaction. Subsequently, miR302a mimics were transfected into esophageal cancer
      cells, and cell viability and invasion were assessed by MTT and Transwell assays.
      In addition, the effects of miR302a on the mitogen-activated protein kinase
      (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling
      pathways were investigated by western blot analysis. The results revealed that
      miR302a expression was significantly decreased in the esophageal cancer cell
      lines compared with a healthy esophagus epithelium cell line. Upregulation of
      miR302a inhibited the proliferation and invasion of esophageal cancer cells, and
      decreased the phosphorylation of extracellular signal-regulated kinase 1/2 and
      Akt. Taken together, the results of the present study indicated that miR302a
      overexpression inhibited the proliferation and invasion of esophageal cancer
      cells through suppression of the MAPK and PI3K/Akt signaling pathways, indicating
      the potential value of miR302a as a treatment target for human esophageal cancer.

PMID- 29456743
TI  - IL-10 in the microenvironment of HNSCC inhibits the CpG ODN induced IFN-alpha
      secretion of pDCs.
AB  - It has been shown that head and neck squamous cell carcinoma (HNSCC) are
      infiltrated by plasmacytoid dendritic cells (pDCs). The HNSCC TH2 biased
      microenvironment leads to strong alterations of the cellular functions of pDC and
      thus impairs the initiation and function of adequate immune responses. In this
      work we comprehensively analyzed the capacity of CpG-oligonucleotides to activate
      interferon (IFN)-alpha secretion of human pDC in the presence of HNSCC. IFN-alpha
      secretion was measured using the ELISA Technique. Class A CpG dinucleotide 2216
      was used in different concentrations and time frames to stimulate the IFN-alpha
      production of human pDC from peripheral blood in the absence and presence of the
      HNSCC microenvironment. To elucidate single components that might induce the
      reduction of IFN-alpha secretion, pDC were exposed to different concentrations of
      HNSCC relevant cytokines such as IL-6, IL-8 and IL-10. In accordance to former
      experiments we found that HNSCC micro milieu severely depresses up to 75% of IFN
      alpha secretion capacity of pDCs, if the stimulating Class A CpG 2216 is added to
      the culture. Preincubation of HNSCC supernatant leads to unrestorable reduction
      of IFN-alpha secretion in pDC and can not be restored by CpG 2216. Incubation of
      pDCs with single cytokines relevant for cancer progression within the HNSCC micro
      milieu show that IL-6 or IL-8 have no influence on the IFN-alpha secretion in
      pDCs, whereas IL-10 massively impairs the secretion in a dose dependent manner.
      This effect can be potentiated by synergistic incubation with IL-6 and can be
      abrogated by blocking antibodies to the IL-10 receptor. Interestingly, incubation
      with IL-10 is not the only factor that impairs the IFN-alpha secretion, as
      incubation with the whole HNSCC supernatant is even more effective in reducing
      the secretion, implying that additional factors play a role. We conclude that
      restoration of HNSCC induced TH2 bias could be improved by the inhibition of
      immune cell cytokine receptors in addition to immunostimulating approaches with
      CpG motifs.

PMID- 29456745
TI  - Sp5 negatively regulates the proliferation of HCT116 cells by upregulating the
      transcription of p27.
AB  - The Wnt signaling pathway is aberrantly activated in the majority of human
      colorectal tumors. beta-catenin, a key component of the Wnt signaling pathway,
      interacts with the T-cell factor/lymphoid enhancer-binding factor family of
      transcription factors and activates transcription of Wnt target genes. Sp5 is one
      of the Wnt target genes, and its expression is commonly upregulated in colon
      cancer cells. The present study demonstrates that the expression of Sp5 is not
      upregulated in the colon cancer cell line HCT116, in which Wnt signaling is
      constitutively activated. Furthermore, the results demonstrate that Sp5 has the
      potential to inhibit cell proliferation through upregulation of the cell cycle
      inhibitor p27. These findings suggest that HCT116 cells downregulate Sp5 to avoid
      p27-mediated growth arrest.

PMID- 29456744
TI  - Cardamonin enhances the anti-proliferative effect of cisplatin on ovarian cancer.
AB  - The mammalian target of rapamycin (mTOR) is well-known as a promising therapeutic
      target in various cancer cells. mTOR activation decreases the sensitivity of
      ovarian cancer to cisplatin. Cardamonin inhibits the proliferation of various
      cancer cells by mTOR suppression. The present study examined whether cardamonin
      combined with cisplatin is efficacious for the anti-proliferation of ovarian
      cancer cells. The anti-proliferative effect was determined by MTT and cell cycle
      assays. Activation of the mTOR signal pathway and the expression of anti
      apoptotic proteins were evaluated by western blot analysis. Cardamonin
      significantly enhanced the effects of cisplatin on cell proliferation and cell
      cycle progression. The expression of B cell lymphoma-2, X-linked inhibitor of
      apoptosis protein and Survivin was significantly decreased following combination
      treatment. Furthermore, the activation of mTOR and its downstream 70 kDa
      ribosomal protein S6 kinase was inhibited by cardamonin. These results
      demonstrated that the combinatorial effects of cardamonin and cisplatin on anti
      proliferation were enhanced by suppressing the expression of anti-apoptotic
      proteins and activation of mTOR in ovarian cancer cells.

PMID- 29456746
TI  - LABOR OMNIA VINCIT IMPROBUS - Labour conquers all things: An Impact Factor for
      JCO!

PMID- 29456747
TI  - Clavicle fracture nonunion in the paediatric population: a systematic review of
      the literature.
AB  - Aims: Clavicle fracture nonunions are extremely rare in children. The aim of this
      systematic review was to assess what factors may predispose children to form
      clavicle fracture nonunions and evaluate the treatment methods and outcomes.
      Methods: We performed a systematic review according to Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses guidelines, aiming to find papers
      reporting clavicle fracture nonunion in children under the age of 18 years. Data
      was collected on patient demographics, fracture type, mechanism of injury (MOI),
      surgical intervention and reported outcome. Two independent reviewers evaluated
      all the data. Results: A total of 13 articles reporting 21 cases of clavicle
      fracture nonunion were identified. The mean age at time of injury was 11.4 years
      (4 to 17). Falls were the most common MOI. The majority of nonunions occurred
      after displaced fractures on the right side. Six were refractures. Mean time of
      presentation following injury was 13.5 months (4 to 60). In all, 16 were treated
      surgically. Radiographic union was eventually achieved in 12 cases, with
      functional outcome satisfactory in all cases. Conclusion: Clavicle nonunion is an
      extremely rare but possible complication in children. The majority occur after
      displaced right-sided fractures or refractures and present around one year after
      injury. Surgical fixation provides good radiographic healing and functional
      outcomes. Level of evidence: IV.

PMID- 29456748
TI  - Wound closure expectations after fasciotomy for paediatric compartment syndrome.
AB  - Purpose: Acute compartment syndrome often requires additional surgery to achieve
      wound closure. Little information exists regarding the expected number of
      surgeries, techniques and complications after closure in paediatric patients.
      Methods: A retrospective chart review identified patients treated for acute
      compartment syndrome at four hospitals over a ten-year period. The cause of
      injury, type of dressing, number of surgeries, type of closure and complications
      were recorded. Results: In all, 32 patients (mean 10.9 years, 1 to 17) who
      underwent 18 lower and 14 upper extremity fasciotomies met inclusion criteria.
      Definitive wound closure technique was delayed primary in 72%, split thickness
      skin graft in 25%, and primary in 3% of patients. Closure required a mean 2.4
      surgeries (0 to 4) over a mean 7.7 days (0 to 34). Days to closure and number of
      surgeries required were not significantly affected by mechanism of injury,
      fasciotomy location or type of dressing used. A total of 23.1% of patients with
      upper extremity and 0% with lower extremity fasciotomies had concerns about the
      scar appearance. Other complications included neurapraxia (6.7%), stiffness
      (6.7%), swelling (3.3%), scar pain (3.3%) and weakness (3.3%). Conclusions: The
      most common complication after paediatric compartment syndrome is an unpleasant
      scar. Wound closure after upper or lower extremity fasciotomies in paediatric
      patients requires a split thickness skin graft in approximately one in four
      patients. However, avoiding a skin graft does not guarantee the absence of
      cosmetic concerns, which are more likely following upper extremity fasciotomies.
      Level of Evidence: IV.

PMID- 29456749
TI  - The effect of canal fill on paediatric femur fractures treated with titanium
      elastic nails.
AB  - Purpose: Traditional teaching for fixation of paediatric femur fractures
      recommends 80% nail diameter/medullary canal diameter ratio (ND/MCD) for
      successful maintenance of reduction. Prior studies have investigated this with
      stainless steel Enders nails. Our aim was to assess the impact of ND/MCD on
      maintenance of reduction and malunion rates in paediatric femur fractures treated
      with flexible intramedullary nails (FINs). Methods: Retrospective data was
      collected on all paediatric patients treated with FINs for diaphyseal femur
      fractures at a single tertiary care institution over a ten-year period. Patients
      with co-morbidities affecting bone quality were excluded. Patients were
      subdivided into groups based on ND/MCD. Results: A total of 66 patients met
      inclusion criteria. Mean ND/MCD was 76.3% (32.9% to 98.8%, SD 14.3). In all, 50%
      (n = 33/66) of patients had > 80% ND/MCD, and only 13.6% (n = 9/66) of patients
      had less than 60% ND/MCD. When controlling for fracture stability, ND/MCD had no
      correlation with mean shortening (p = 0.07) There was no correlation between
      ND/MCD and angulation in the sagittal (p = 0.96) or coronal plane (p = 0.20).
      Three patients fit malunion criteria. ND/MCD for these patients were 40%, 67% and
      79%. Conclusion: There was no correlation between ND/MCD and shortening or
      malangulation. The majority of patients in this series with less than 80% fill
      with FIN healed within acceptable parameters. Level of Evidence: III.

PMID- 29456750
TI  - Paediatric tibial shaft fractures treated by open reduction and stabilization
      with monolateral external fixation.
AB  - Purpose: Elastic stable intramedullary nailing is increasingly used for surgical
      treatment of tibial shaft fractures, but frequently requires immobilization and
      delayed full weight-bearing. Therefore, external fixation remains interesting.
      The aim was to report clinico-radiological outcomes of monolateral external
      fixation for displaced and unstable tibial shaft fractures in children. Methods:
      All tibial fractures consecutively treated by monolateral external fixation
      between 2008 and 2013 were followed. Inclusion criteria included skeletal
      immaturity and closed and open Gustilo I fractures caused by a direct impact.
      Patients were seen until two years postoperatively. Demographics, mechanism of
      injury, surgical data and complications were recorded. Anteroposterior and
      lateral side radiographs were performed at each visit. Full-limb 3D
      reconstructions using biplanar stereroradiography was performed for final limb
      length and alignment measures. Results: A total of 45 patients (mean age 9.7
      years +/- 0.5) were included. In all, 17 were Gustilo I fractures, with no
      difference between open and closed fractures for any data. Mean time to full
      weight bearing was 18.2 days +/- 0.7. After 15 days, 39 patients returned to
      school. Hardware removal (mean time to union 15.6 weeks +/- 0.8) was performed
      during consultation under analgesic gas. There were no cases of nonunion. No
      fracture healed with > 10 degrees  of angulation (mean 5.1 degrees  +/- 0.4
      degrees ). Leg-length discrepancy > 10 mm was found for six patients.
      Conclusions: This procedure can be a safe and simple surgical treatment for
      children with tibial shaft fractures. Few complications and early return to
      school were reported, with the limitations of non-comparative study. Level of
      Evidence: IV.

PMID- 29456751
TI  - Cannulated screw versus Kirschner-wire fixation for Milch II lateral condyle
      fractures in a paediatric sawbone model: a biomechanical comparison.
AB  - Purpose: Lateral condyle fractures of the humerus are common in the paediatric
      population, accounting for up to 20% of elbow fractures. Traditional management
      involves internal fixation with Kirschner (K)-wires, however, this has been
      associated with complications and insufficiently rigid fixation. Recently,
      cannulated screws have been proposed as a more stable method of fixation. While
      cannulated screws have been thought to allow earlier range of movement and
      shorten time to union, data regarding the biomechanical performance and optimal
      screw placement is scarce. We hypothesize that cannulated screw fixation is
      superior to K-wire fixation and screw placement can enhance the stability of the
      construct. Methods: Paediatric humerus sawbones with Milch II fractures were
      fixed with one of three methods. Fractures were reduced with either a single
      cannulated screw either through the centre of the capitellum (oblique), or placed
      up the lateral column across the growth plate (lateral), or fixed with two K
      wires. Fixed sawbone fractures were then mechanically tested in two directions
      simulating in vivo forces. Results: The lateral screw construct had a higher
      maximum force to failure, higher stiffness and absorbed higher energy as compared
      with the K-wire fixation and oblique screw under an anterior force. When loaded
      from the posterior direction, only the lateral column screw was better than K
      wire fixation. Conclusions: Screw fixation is a biomechanically effective
      alternative to K-wire fixation, especially when placed up the lateral column of
      the distal humerus. Further clinical studies are required before transcapitellar
      screw fixation can be adopted.

PMID- 29456752
TI  - Treatment of the overriding fifth toe: Butler's arthroplasty is a good option.
AB  - Purpose: The overriding fifth toe is a congenital triplane deformity that may
      cause aesthetic and functional concerns in children and adolescents. This study
      aims to evaluate the results obtained when using Butler's arthroplasty to treat
      this forefoot deformity. Methods: We performed a retrospective study, including
      all patients undergoing Butler's arthroplasty from January 1995 to December 2012.
      Clinical records were reviewed to determine age at date of surgery, gender,
      laterality, preoperative symptoms, success of deformity correction, postoperative
      pain, scarring, need for adapted shoe, rates of complications and recurrence.
      Patient satisfaction was evaluated through a telephone interview. All p-values <
      0.05 were considered statistically significant. Results: A total of 21 patients
      were included in this study, the majority of which were male (57%), with a mean
      follow-up of 12 months (1 to 52). In the evaluation of the residual deformity (18
      patients), 72% had excellent results, 17% good and 11% poor results. One patient
      had a keloid scar, three patients reported pain and three patients required
      adapted footwear. There was a partial recurrence of the deformity in three cases.
      The majority of patients (78%) were satisfied with the surgery. There was no
      statistically significant difference in terms of results, when comparing patients
      older and younger than seven years of age (p = 0.46). Conclusions: Butler's
      operation is effective and safe in the treatment of the overriding fifth toe,
      yielding good functional results and patient satisfaction, with low rate of
      complications. Level of Evidence: IV.

PMID- 29456753
TI  - Subtalar coalition resection utilizing live navigation: a technique tip.
AB  - Purpose: Describe the surgical technique of talocalcaneal coalition resection
      using live CT navigation. Methods: A ten-year-old female with left talocalcaneal
      coalition hindfoot pain refractory to conservative management underwent surgical
      coalition resection using live CT navigation. The procedure and discussion of
      this technique is described in detail. Results: With minimal radiation exposure
      to the patient, CT navigation for this complex talocalcaneal coalition was both
      helpful and potentially timesaving by allowing immediate localization and guided
      resection of the coalition. Conclusion: In the case of a complex subtalar
      coalition resection, CT navigation poses minimal patient radiation exposure and
      allows immediate localization and guided resection of the coalition. Level of
      Evidence: Level V.

PMID- 29456754
TI  - Management of osteonecrosis of the femoral head in children with sickle cell
      disease: results of conservative and operative treatments at skeletal maturity.
AB  - Purpose: Sickle cell disease (SCD) is the most common cause of femoral head
      osteonecrosis (ONFH) during childhood with an overall prevalence of 10%. In
      children, spontaneous revascularization can occur, as in Legg-Calve-Perthes
      disease. Consequently, the aim of treatment is to restore proper hip containment
      to prevent joint arthritis. This is the first study reporting long-term results
      at skeletal maturity of non-operative and surgical treatments for ONFH in SCD
      children. Methods: All children with ONFH due to SCD were retrospectively
      reviewed. At initial evaluation, extension of osteonecrosis was radiographically
      defined using Catterall, lateral pillar Herring and Ficat classifications.
      Subluxation of the femoral head with Reimers migration index > 30% required
      surgical treatment including femoral varus osteotomy and/or pelvic osteotomies.
      Conservative treatment including non-weight bearing and physiotherapy was
      performed in the remaining cases. Outcomes were assessed at skeletal maturity
      using the Harris Hip Score (HHS) and the Stulberg classification. Total hip
      arthroplasty and Stulberg 5 were defined as failures. Results: A total of 25 hips
      in 17 patients were included (mean follow-up 7.5 years SD 3.4). Mean age at
      diagnosis was 11.4 years SD 2.9. In all, 15 hips (60%) were classified Catterall
      3 and 4 and Herring B and C. A total of 13 patients (52%) underwent surgical
      treatment. At skeletal maturity, mean HHS was good (81 SD 17), 12 hips (48%) were
      classified Stulberg 1 and 2, seven hips (28%) were classified Stulberg 3 and 4.
      Conclusion: Both treatments led to good functional results with 75% of congruent
      hips at skeletal maturity. Level of Evidence: IV.

PMID- 29456755
TI  - Preliminary results of an anteverting triple periacetabular osteotomy for the
      treatment of hip instability in Down syndrome.
AB  - Purpose: To investigate the outcomes of an anteverting triple periacetabular
      osteotomy for the treatment of hip instability in skeletally immature patients
      with Down syndrome. Methods: We evaluated 16 patients (21 hips) with Down
      syndrome and hip instability who underwent an anteverting triple periacetabular
      osteotomy between 2007 and 2016. There were nine females and seven males with an
      average age of 7.4 years SD 2.0. We assessed the level of hip pain, gait ability
      and clinical stability at a minimum of one year after surgery. Radiographic
      evaluation included pre- and postoperative lateral centre-edge angle (LCEA),
      Tonnis acetabular angle and extrusion index. Result: After an average follow-up
      of 4.1 years SD 2.6, 20 of 21 hips (95%) remained clinically stable. In all, 12
      of 16 (75%) patients had a full gait without a major limp, but three patients
      (19%) had a persistent limp. Of the 21 procedures, one hip (5%) was considered a
      failure due to persistent instability. There was a mean increase of 18.3o SD
      15.3o of the LCEA (p < 0.001); a mean decrease of 15.2o SD 11.6o (p < 0.001) for
      the Tonnis angle and the extrusion index had a mean decrease of 0.27 SD 0.20 (p <
      0.001). The most common complications were minor and included nonunion of the
      pubis or ischium (24%) and stress fractures of the pubis and ischium (14%). Only
      one patient required unplanned surgery for the treatment of an infection; which
      was considered a major complication. Conclusion: The anteverting triple
      periacetabular osteotomy provided global deformity correction and achieved hip
      stability in 95% of the hips after a mean follow-up of 4.1 years. Level of
      Evidence: Therapeutic level IV.

PMID- 29456756
TI  - Relationship between thoracic kyphosis and neural axis abnormalities in patients
      with adolescent idiopathic scoliosis.
AB  - Purpose: Previous studies have suggested an association between increased
      thoracic kyphosis and neural axis abnormalities in patients with adolescent
      idiopathic scoliosis (AIS). However, the basis for this finding is unclear, and
      this association has been mainly noted in retrospective studies on a non
      consecutive series of patients. The purpose of this study was to assess the
      relationship between thoracic kyphosis and neural axis abnormalities in patients
      with AIS. Methods: We studied a consecutive series of AIS patients treated with
      spinal fusion. Thoracic kyphosis (T2 to T12) was measured from preoperative
      lateral radiographs. All patients underwent a spine magnetic resonance imaging
      (MRI) prior to surgery, and MRI reports were reviewed to determine the presence
      of neural axis abnormalities. Statistical analyses included descriptive
      statistics and chi-squared analysis. Results: This study included 210 patients
      with AIS. There were no significant differences in age or gender between patients
      with thoracic hypokyphosis (kyphosis < 20 degrees ), normal thoracic kyphosis
      (kyphosis 20 degrees  to 40 degrees ) and thoracic hyperkyphosis (kyphosis > 40
      degrees ) (p > 0.05). Neural axis abnormalities were present in 17.9% of patients
      with thoracic hypokyphosis, 9.8% of patients with normal thoracic kyphosis and
      13.6% of patients with thoracic hyperkyphosis (p = 0.60). There were no
      significant differences in rates of Chiari malformation, syrinx, intra-spinal
      masses and other central nervous system abnormalities between groups (p > 0.05).
      Conclusions: Thoracic kyphosis was not associated with neural axis abnormalities
      in our consecutive series of patients with AIS. Increased thoracic kyphosis may
      not be a reliable indicator for the presence of neural axis abnormalities in
      patients with AIS. Level of Evidence: IV.

PMID- 29456757
TI  - The natural history of spinal deformity in patients with Coffin-Lowry syndrome.
AB  - Purpose: Little is known about the natural history of spinal deformities in
      Coffin-Lowry syndrome (CLS). Our goal was to evaluate the spinal deformity
      progression and clinical impact. Methods: In this institutional review board
      approved study, we performed a multinational retrospective review of six male CLS
      patients, aged 13 to 22 years at final follow-up, for a mean of 7.25 years (3 to
      13). Results: All showed delayed skeletal maturity. Three had calcifications of
      their lower cervical ligamentum flavum, all experienced neural axis
      abnormalities, including lower extremity weakness, numbness and tingling and in
      one, quadriparesis. Only two were ambulatory at final follow-up.All had
      significant spinal abnormalities, including severe progressive thoracic lordosis,
      thoracolumbar kyphosis and scoliosis. All had undergone spinal fusion or were
      being evaluated for surgery. Conclusion: CLS is a rare X-linked mutation in the
      RSK2 gene, affecting between 1/50 000 to 100 000 people. There are two reports in
      the literature of patients with calcifications of their ligamentum flavum. Both
      had neural axis abnormalities and one had acute onset quadriplegia. Analysis of
      their ligamentum flavum found abundant central calcifications. Despite our small
      cohort we found 50% had calcifications and 100% had neurologic consequences
      associated with those calcifications. There was a 100% rate of deformity
      progression.They all exhibited delay in skeletal maturity, which mandates longer
      follow-up and has implications for surgical planning.From our cohort and
      literature review, the natural history of CLS supports frequent patient
      evaluation and a lower threshold for correction of spinal deformities. Aiming to
      avoid spinal cord compression and improve or avoid neurological deterioration.
      Level of Evidence: IV - retrospective study.

PMID- 29456758
TI  - Binary and analogue markers of skeletal maturity: clinical utility of the thenar
      and plantar sesamoids.
AB  - Purpose: We investigate the thenar and plantar sesamoids as markers of skeletal
      maturity, and grade appearance using two scales, a binary system (absent or
      present), and an analogue system that relies upon judging regular changes in
      morphological appearance. Methods: We studied 94 healthy children (49 female and
      45 male patients) between ages three and 18 years who had approximately 700
      serially acquired sets of radiographs and physical examinations. The children had
      at least annual radiographs taken of the left hand and left foot. Velocity of
      growth was calculated and curves were fit to a cubic spline model to determine
      age of maximum height velocity, or peak height velocity (PHV). Appearance of the
      plantar and thenar sesamoids was recorded using a binary system classifying the
      sesamoids as absent or present and an analogue system classifying the sesamoid as
      absent, present as a small ossification centre or larger than a small
      ossification centre. Results: The plantar sesamoids appear 1.67 years before PHV
      and reach mature size 1.02 years after PHV. The thenar sesamoids appear 0.32
      years before PHV and reach mature size 2.25 years after PHV. The plantar
      sesamoids are present and thenar sesamoids are absent at a mean 1.5 years prior
      to PHV. No patients had the thenar sesamoids present while the plantar sesamoids
      were absent. Conclusion: As binary markers, when the plantar and thenar sesamoids
      are considered together it is possible to localize maturity. As analogue markers,
      they offer more information. The sesamoids also allow clarification of the
      calcaneal and Sanders stages. Level of Evidence: Not Applicable.

PMID- 29456759
TI  - Ossification of the phalanges of the foot and its relationship to peak height
      velocity and the calcaneal system.
AB  - Purpose: There are multiple skeletal maturity grading systems, but none of them
      utilizes the phalanges of the foot. To minimize radiation, it would be ideal if
      one could assess the skeletal maturity of a foot based on bones seen on routine
      foot radiographs, if guided growth is being considered as a treatment option. We
      developed a system that correlates changes of the appearance of the foot
      phalanges to peak height velocity (PHV) and the recently described calcaneal
      apophyseal ossification grading system. Methods: We selected 94 children from the
      Bolton-Brush study, each with consecutive radiographs from age ten to 15 years
      old. Using the anteroposterior view, we analyzed the ossification patterns of the
      phalanges and developed a six-stage system. We then determined the PHV for each
      subject and defined its relationship with our system. Our system was then
      compared with the previously established calcaneal system. Results: We calculated
      an Intraclass correlation coefficient (ICC) range of 0.957 to 0.985 with a mean
      of 0.975 and interclass reliability coefficient of 0.993 indicating that this
      method is reliable and consistent. Our system showed no significant difference
      between gender with respect to PHV, which makes it a reliable surrogate for
      determining bone age in paediatric and adolescent patients. Conclusions: Our
      system has a strong association with the calcaneal system. It is a simple six
      stage system that is reliable and correlated more strongly with PHV than
      chronological age. The system requires knowledge of the ossification markers used
      for each stage but is easily used in a clinical setting.

PMID- 29456760
TI  - Guided growth: preliminary results of a multinational study of 967 physes in 537
      patients.
AB  - Background: Guided growth by tension band plating is commonly used to correct
      coronal plane deformity. The purpose of this study was to measure the effect and
      further define parameters that influence results in coronal plane deformity
      around the knee. Methods: The retrospective multicentre study included data on
      967 physes in 537 patients, with an average follow-up of 16 months after plate
      insertion. Alignment analysis was compared preoperatively and in at least two
      measurements postoperatively, as well as with parameters that influence the rate
      and amount of correction. Results: Average age at plate implantation was 11.35
      years (SD 3.29).Of those with femoral deformities, 85% of the patients finished
      the treatment and of those, 70% were corrected to standard alignment, while 14%
      have not yet achieved correction, and are still growing.Of those with tibial
      deformities, 75% of the patients finished the treatment and of those 80% were
      corrected to standard alignment, while 25% have not yet achieved correction and
      are still growing.The calculated rate of correction was 0.77 degrees /month for
      the femur and 0.79 degrees /month for the tibia.In terms of complications, the
      overall rate of infection was 1.48%. In three patients (0.55%) screw breakage was
      recorded.Factors found to significantly influence the amount of correction were
      age at plate implantation and direction of deformity. Conclusion: Temporary
      hemiepiphysiodesis takes the advantage of physiological physeal growth to
      effectively treat angular deformities. Success of treatment is influenced by the
      age of the patient at plate implantation and direction of deformity. Level of
      Evidence: IV.

PMID- 29456761
TI  - Effects of a telescopic intramedullary rod for treating patients with
      osteogenesis imperfecta of the femur.
AB  - Purpose: To introduce a new model of telescopic intramedullary rod (TIR),
      evaluate its effects on treating patients presenting with moderate and severe
      osteogenesis imperfecta (OI) and to compare the findings with those of other
      telescopic rods. Methods: A total of 21 patients (nine girls and 12 boys; mean
      age at first operation, 6.6 years, 1.52 to 13.18) who underwent 52 femoral
      operations were monitored during a mean of 9.96 years (3.39 to 14.54). Patient
      characteristics, telescoping rod capability and its complications were examined.
      Results: According to the Sillence classification, we investigated one patient
      with type I, nine with type III and 11 with type IV OI. Revision rates at up to
      five years (36%) were inferior to those found for the Fassier-Duval rod (46%).
      The main cause of revision was fracture (15 patients), followed by rod migration
      (nine), and infection (two). The rod exhibited higher telescopic capacity in boys
      than girls. Type III most commonly required an operation; the age group with the
      highest number of procedures was five to ten years. Male migration was the main
      cause of rod migration. Conclusion: The TIR has a satisfactory cost-benefit ratio
      with less complication rates and low production costs. The TIR is a feasible
      alternative to the commonly used Fassier-Duval rod. Level of Evidence: IV.

PMID- 29456762
TI  - A Cloud-Ozone Data Product from Aura OMI and MLS Satellite Measurements.
AB  - Ozone within deep convective clouds is controlled by several factors involving
      photochemical reactions and transport. Gas-phase photochemical reactions and
      heterogeneous surface chemical reactions involving ice, water particles, and
      aerosols inside the clouds all contribute to the distribution and net production
      and loss of ozone. Ozone in clouds is also dependent on convective transport that
      carries low troposphere/boundary layer ozone and ozone precursors upward into the
      clouds. Characterizing ozone in thick clouds is an important step for quantifying
      relationships of ozone with tropospheric H2O, OH production, and cloud
      microphysics/transport properties. Although measuring ozone in deep convective
      clouds from either aircraft or balloon ozonesondes is largely impossible due to
      extreme meteorological conditions associated with these clouds, it is possible to
      estimate ozone in thick clouds using backscattered solar UV radiation measured by
      satellite instruments. Our study combines Aura Ozone Monitoring Instrument (OMI)
      and Microwave Limb Sounder (MLS) satellite measurements to generate a new
      research product of monthly-mean ozone concentrations in deep convective clouds
      between 30 degrees S to 30 degrees N for October 2004 - April 2016. These
      measurements represent mean ozone concentration primarily in the upper levels of
      thick clouds and reveal key features of cloud ozone including: persistent low
      ozone concentrations in the tropical Pacific of ~10 ppbv or less; concentrations
      of up to 60 pphv or greater over landmass regions of South America, southern
      Africa, Australia, and India/east Asia; connections with tropical ENSO events;
      and intra-seasonal/Madden-Julian Oscillation variability. Analysis of OMI aerosol
      measurements suggests a cause and effect relation between boundary layer
      pollution and elevated ozone inside thick clouds over land-mass regions including
      southern Africa and India/east Asia.

PMID- 29456763
TI  - Causal effect of smoking on DNA methylation in peripheral blood: a twin and
      family study.
AB  - Background: Smoking has been reported to be associated with peripheral blood DNA
      methylation, but the causal aspects of the association have rarely been
      investigated. We aimed to investigate the association and underlying causation
      between smoking and blood methylation. Methods: The methylation profile of DNA
      from the peripheral blood, collected as dried blood spots stored on Guthrie
      cards, was measured for 479 Australian women including 66 monozygotic twin pairs,
      66 dizygotic twin pairs, and 215 sisters of twins from 130 twin families using
      the Infinium HumanMethylation450K BeadChip array. Linear regression was used to
      estimate associations between methylation at ~ 410,000 cytosine-guanine
      dinucleotides (CpGs) and smoking status. A regression-based methodology for
      twins, Inference about Causation through Examination of Familial Confounding (ICE
      FALCON), was used to assess putative causation. Results: At a 5% false discovery
      rate, 39 CpGs located at 27 loci, including previously reported AHRR, F2RL3,
      2q37.1 and 6p21.33, were found to be differentially methylated across never,
      former and current smokers. For all 39 CpG sites, current smokers had the lowest
      methylation level. Our study provides the first replication for two previously
      reported CpG sites, cg06226150 (SLC2A4RG) and cg21733098 (12q24.32). From the ICE
      FALCON analysis with smoking status as the predictor and methylation score as the
      outcome, a woman's methylation score was associated with her co-twin's smoking
      status, and the association attenuated towards the null conditioning on her own
      smoking status, consistent with smoking status causing changes in methylation. To
      the contrary, using methylation score as the predictor and smoking status as the
      outcome, a woman's smoking status was not associated with her co-twin's
      methylation score, consistent with changes in methylation not causing smoking
      status. Conclusions: For middle-aged women, peripheral blood DNA methylation at
      several genomic locations is associated with smoking. Our study suggests that
      smoking has a causal effect on peripheral blood DNA methylation, but not vice
      versa.

PMID- 29456764
TI  - Integrative analysis of the epigenetic basis of muscle-invasive urothelial
      carcinoma.
AB  - Background: Elucidation of epigenetic alterations in bladder cancer will lead to
      further understanding of the biology of the disease and hopefully improved
      therapies. Our aim was to perform an integrative epigenetic analysis of invasive
      urothelial carcinoma of the bladder to identify the epigenetic abnormalities
      involved in the development and progression of this cancer. Methods: Pre
      processed methylation data and RNA-seq data were downloaded from The Cancer
      Genome Atlas (TCGA) and processed using the R package TCGA-Assembler. An R
      package MethylMix was used to perform an analysis incorporating both methylation
      and gene expression data on all samples, as well as a subset analysis comparing
      patients surviving less than 2 years and patients surviving more than 2 years.
      Genes associated with poor prognosis were individually queried. Pathway analysis
      was performed on statistically significant genes identified by MethylMix criteria
      using ConsensusPathDB. Validation was performed using flow cytometry on bladder
      cancer cell lines. Results: A total of 408 patients met all inclusion criteria.
      There were a total of 240 genes differentially methylated by MethylMix criteria.
      Review of individual genes specific to poor-prognosis patients revealed the
      majority to be candidate tumor suppressors in other cancer types. Pathway
      analysis showed increase in methylation of genes involved in antioxidant pathways
      including glutathione and NRF2. Genes involved in estrogen metabolism were also
      hypermethylated while genes involved in the EGFR pathway were found to be
      hypomethylated. EGFR expression was confirmed to be elevated in six bladder
      cancer cell lines. Conclusions: In patients with invasive urothelial carcinoma,
      we found differential methylation in patients with better and worse prognosis
      after cystectomy. Differentially methylated genes are involved in many relevant
      oncologic pathways, including EGFR and antioxidant pathways, that may be a target
      for therapy or chemoprevention.

PMID- 29456765
TI  - Peripheral blood epi-signature of Claes-Jensen syndrome enables sensitive and
      specific identification of patients and healthy carriers with pathogenic
      mutations in KDM5C.
AB  - Background: Claes-Jensen syndrome is an X-linked inherited intellectual
      disability caused by mutations in the KDM5C gene. Kdm5c is a histone lysine
      demethylase involved in histone modifications and chromatin remodeling. Males
      with hemizygous mutations in KDM5C present with intellectual disability and
      facial dysmorphism, while most heterozygous female carriers are asymptomatic. We
      hypothesized that loss of Kdm5c function may influence other components of the
      epigenomic machinery including DNA methylation in affected patients. Results:
      Genome-wide DNA methylation analysis of 7 male patients affected with Claes
      Jensen syndrome and 56 age- and sex-matched controls identified a specific DNA
      methylation defect (epi-signature) in the peripheral blood of these patients,
      including 1769 individual CpGs and 9 genomic regions. Six healthy female carriers
      showed less pronounced but distinctive changes in the same regions enabling their
      differentiation from both patients and controls. Highly specific computational
      model using the most significant methylation changes demonstrated 100% accuracy
      in differentiating patients, carriers, and controls in the training cohort, which
      was confirmed on a separate cohort of patients and carriers. The 100% specificity
      of this unique epi-signature was further confirmed on additional 500 unaffected
      controls and 600 patients with intellectual disability and developmental delay,
      including other patient cohorts with previously described epi-signatures.
      Conclusion: Peripheral blood epi-signature in Claes-Jensen syndrome can be used
      for molecular diagnosis and carrier identification and assist with interpretation
      of genetic variants of unknown clinical significance in the KDM5C gene.

PMID- 29456766
TI  - Letter to the editor: blood processing and sample storage have negligible effects
      on methylation.
AB  - DNA methylation is a dynamic epigenetic mechanism. Researchers aiming to assess
      archived DNA samples are expressing concern about the effect of technical factors
      on methylation, as this may confound results. We reviewed recent reports
      examining this issue in blood samples and concluded that variation in collection,
      storage, and processing of blood DNA confers negligible effects on both global
      methylation and methylation status of specific genes. These results are
      concordant with studies that have investigated the effect of sample storage and
      processing on methylation in other tissues, such as tumour, sperm, and placenta
      samples.

PMID- 29456767
TI  - Biochemical Characterization of Two Clinically-Relevant Human Fumarase Variants
      Defective for Oligomerization.
AB  - Background: Fumarase, a significant enzyme of energy metabolism, catalyzes the
      reversible hydration of fumarate to L-malate. Mutations in the FH gene, encoding
      human fumarase, are associated with fumarate hydratase deficiency (FHD) and
      hereditary leiomyomatosis and renal cell cancer (HLRCC). Fumarase assembles into
      a homotetramer, with four active sites. Interestingly, residues from three of the
      four subunits within the homotetramer comprise each active site. Hence, any
      mutation affecting oligomerization is predicted to disrupt enzyme activity.
      Methods: We constructed two variants of hexahistidine-tagged human recombinant
      fumarase, A308T and H318Y, associated with FHD and HLRCC, respectively. Both
      Ala308 and His318 lie within the fumarase intersubunit interface. We purified
      unmodified human fumarase and the two variants, and analyzed their enzymatic
      activities and oligomerization states in vitro. Results: Both variants showed
      severely diminished fumarase activity. Steady-state kinetic analysis demonstrated
      that the variants were largely defective due to decreased turnover rate, while
      displaying Km values for L-malate similar to unmodified human recombinant
      fumarase. Blue native polyacrylamide gel electrophoresis and gel filtration
      experiments revealed that each variant had an altered oligomerization state,
      largely forming homodimers rather than homotetramers. Conclusion: We conclude
      that A308T and H318Y render human fumarase enzymatically inactive via defective
      oligomerization. Therefore, some forms of FHD and HLRCC can be linked to
      improperly folded quaternary structure.

PMID- 29456768
TI  - Hospital Mortality Among Elderly Patients Admitted With Neurological Disorders
      Was Not Predicted by any Particular Diagnosis in a Tertiary Medical Center.
AB  - Background: Neurological disorders (NDs) are associated with high hospital
      mortality. We aimed to identify predictors of hospital mortality among elderly
      inpatients with NDs. Methods: Patients aged >=60 years admitted to the hospital
      between January 1, 2009 and December 31, 2010 with acute NDs, chronic NDs as
      underpinnings of acute clinical disorders, and neurological complications of
      other diseases were studied. We analyzed demographic data, NDs, and comorbidities
      as independent predictors of hospital mortality. Logistic regression was
      performed for multivariable analysis. Results: Overall, 1540 NDs and 2679
      comorbidities were identified among 798 inpatients aged >= 60 years (mean 75.8+/
      9.1). Of these, 54.5% were female. Diagnostic frequency of NDs ranged between
      0.3% and 50.8%. Diagnostic frequency of comorbidities ranged from 5.6% to 84.5%.
      Comorbidities varied from 0 to 9 per patient (90% of patients had >=2
      comorbidities), mean 3.2+/-1.47(CI, 3.1-3.3). Patients with multimorbidities
      presented with a mean of 4.7+/-1.7 morbidities per patient. Each ND and
      comorbidity were associated with high hospital mortality, producing narrow ranges
      between the lowest and highest incidences of death (hospital mortality = 18%)
      (95% CI, 15%-21%). After multivariable analysis, advanced age (P<0.001) and low
      socioeconomic status (P=0.003) were recognized as predictors of mortality,
      totaling 9% of the variables associated with hospital mortality. Conclusion:
      Neither a particular ND nor an individual comorbidity predicted hospital
      mortality. Age and low socioeconomic class accounted for 9% of predictors. We
      suggest evaluating whether functional, cognitive, or comorbidity scores will
      improve the risk model of hospital mortality in elderly patients admitted with
      ND.

PMID- 29456769
TI  - A Case of Schwannoma of the Submandibular Region.
AB  - Background: We herein described a rare case of schwannoma of the hypoglossal
      nerve in the submandibular region with diagnostic imaging and histopathological
      findings. Case Report: A 31-years-old woman has had a palpable firm, rubbery,
      freely mobile mass in the submandibular region. Of imaging, MR images showed
      homogeneous isointensity on T1-weighted imaging (T1-WI), heterogeneous
      hypointensity on T2-WI, heterogeneous hyperintensity on short T1 inversion
      recovery (STIR), and heterogeneous enhancement on contrast-enhanced T1-WI. A
      clear capsule was observed on the margin and showed hypointense on T2-WI. Dynamic
      MRI showed heterogeneous gradual increased enhancement. The uptake of contrast
      medium was regionally slow. Diagnostic imaging using CT and MRI was suspected of
      salivary gland tumor or neurogenic tumor. In consideration of imaging diagnosis,
      a pleomorphic adenoma or a schwannoma was suspected. Final diagnosis was
      confirmed on the basis of histopathological finding and intraoperative findings.
      Conclusion: 1. Histopathologic examination is inevitable, because MR findings are
      not specific.2. Schwannomas were said to have specific MRI properties, including
      specific signs (split-fat sign, fascicular sign, target sign). However, they are
      not always observed.3. This case confirmed the differential diagnosis on the
      basis of the intraoperative finding that the tumor was continuous with the
      hypoglossal nerve.

PMID- 29456770
TI  - Recurrent Oral Eosinophilic Ulcers of the Oral Mucosa. A Case Report.
AB  - Objective: This article describes a case of an Oral Eosinophilic Ulcer (OEU) in
      an otherwise healthy 31-year-old white woman. Introduction: The importance of
      reporting this case was the presence of recurrent episodes with lesions appearing
      in different areas of the oral mucosa, a type of manifestation not commonly
      associated with this disease. A typical manifestation of OEU occurs as a single
      ulceration that goes into healing after an incisional biopsy, a procedure usually
      required for a proper diagnosis of the disease. In spite of trauma being
      suggested as the main culprit of OEU, the exact pathogenesis mechanism of this
      disease remains controversial. Case report: The pattern of the present case
      contradicts the usually common course of the disease, as the patient had
      experienced many recurrent episodes for almost 2.5 years, with the recurrences
      occurring even after biopsies performed during some of the relapses. Differential
      diagnosis included recurrent aphthous stomatitis, recurrent intra-oral herpes,
      autoimmune disease, Crohn's disease and malignancy. Conclusion: Fortunately, the
      patient has been free of any recurrences for 1.5 years since the last biopsy was
      taken at the time she came to our clinic seeking treatment.

PMID- 29456771
TI  - Pulpal and Periodontal Tissues Changes Associated with Le Fort I and Sagittal
      Split Ramus Osteotomies: A review.
AB  - Introduction: Le Fort I and sagittal split ramus osteotomies are the most
      commonly performed orthognathic surgery procedures on the maxilla and mandible,
      respectively. Techniques: Despite progress in the techniques, these procedures
      may still be associated with morbidity, expressed as inflammation, inadequate
      bony union, periodontal damages or in extreme cases even total bone loss.
      Discussion: Through a comprehensive review of the literature, the influences of
      maxillary and mandibular surgery on Pulpal Blood Flow (PBF), pulp sensitivity and
      pulp vitality are examined. Moreover, adverse effects of maxillary surgery on
      tooth color and periodontal tissues are also reported. The effects had a variety
      of expression. Concerning maxillary surgery, some studies showed an initial
      increase in PBF followed by a decrease to the baseline or even lower levels after
      1-3 months. Other studies found an initial decrease in PBF followed by an
      increase soon after. There were also studies that showed no significant PBF
      changes, in contrast. Conclusion: Concerning mandibular surgery, a recent study
      showed a decrease in PBF immediately after sagittal split ramus osteotomy. Some
      authors detected tooth discoloration of maxillary teeth after Le Fort I
      osteotomy. Root resorption and root injury were also detected, but were of minor
      significance. Usually, these adverse effects derive from injury of the vessels of
      the palatal pedicle. This pedicle should be maintained intact for the avoidance
      of blood flow impairments. In addition, the descending palatine artery should be
      protected during maxillary surgery procedures in order to maintain the highest
      possible blood flow on the maxillary teeth.

PMID- 29456772
TI  - Multidimensional Analysis of Curved Root Canal Preparation Using Continuous or
      Reciprocating Nickel-titanium Instruments.
AB  - Objective: To evaluate transportation (T) and centering ability (CA) of root
      canal preparations using continuous or reciprocating nickel-titanium endodontic
      files. Materials and Methods: Ninety-six mesiobuccal root canals of mandibular
      first and second molars were randomly divided into 6 groups (n=16) according to
      the rotary file used: 1. ProTaper Next; 2. ProTaper Gold; 3. Mtwo; 4. BioRaCe; 5.
      WaveOne Gold; 6. Reciproc. Root canals were prepared according to manufacturer's
      instructions. Cone beam computed tomography scans were obtained before and after
      root canal preparation. Measurements were made at six different reference points:
      2, 3 and 4 mm from the apex and 2, 3 and 4 mm below furcation in different
      directions. Results: The greatest Mesiodistal (MD) Transportation (T) was found
      for Reciproc files (p<0.05), and the greatest buccolingual (BL) T, for Reciproc,
      ProTaper Gold and ProTaper Next files (p<0.05). The greatest Mesiodistal (MD)
      Centering Ability (CA) was found for BioRaCe files (p<0.05), and the greatest
      Buccolingual (BL) CA, for BioRaCe and Mtwo files (p<0.05). Conclusion: All
      systems produced root canal transportation. No file system achieved perfect CA of
      root preparation. Reciproc files had the greatest MD T and BL T. BioRaCe files
      had the greatest MD CA, whereas BL CA was similar for BioRaCe and Mtwo files.

PMID- 29456773
TI  - Molecular Characterization of Multidrug Resistant Uropathogenic E. Coli Isolates
      from Jordanian Patients.
AB  - Background: Emergence of multi-drug resistant uropathogenic E. coli strains is an
      increasing problem to empirical treatment of urinary tract infections in many
      countries. This study investigated the magnitude of this problem in Jordan.
      Methods: A total of 262 E. coli isolates were recovered from urine samples of
      Jordanian patients which were suspected to have urinary tract infections (UTIs).
      All isolates were primarily identified by routine biochemical tests and tested
      for antimicrobial susceptibility by disc diffusion method. Fifty representative
      Multidrug Resistance (MDR) E. coli isolates to 3 or more antibiotic classes were
      tested for the presence of resistance genes of blaCTX-M- 1, 9 and 15,
      carbapenemase (blaIMP, blaVIM, blaNDM-1, blaOXA-48), fluoroquinolones mutated
      genes (parC and gyrA) and clone of ST131 type using PCR methods. Results: A total
      of 150/262 (57.3%) of E. coli isolates were MDR. Urine samples of hospitalized
      patients showed significantly more MDR isolates than outpatients. Fifty
      representative MDR E. coli isolates indicated the following molecular
      characteristics: All were positive for mutated parC gene and gyrA and for ST131
      clone, and 78% were positive for genes of CTX-M-15, 76% for CTX-M-I and for 8%
      CTX-M-9, respectively. Additionally, all 50 MDR E. coli isolates were negative
      for carbapenemase genes (blaIMP, blaVIM, blaNDM-1, blaOXA-48), except of one
      isolate was positive for blaKPC-2 . Conclusion: This study indicates alarming
      high rates recovery of MDR uropathogenic E. coli from Jordanian patients
      associated with high rates of positive ST131 clone, fluoroquinolone resistant and
      important types of blaCTX-M.

PMID- 29456774
TI  - Gastric Aspiration and Its Role in Airway Inflammation.
AB  - Gastro-Oesophageal Reflux (GOR) has been associated with chronic airway diseases
      while the passage of foreign matter into airways and lungs through aspiration has
      the potential to initiate a wide spectrum of pulmonary disorders. The clinical
      syndrome resulting from such aspiration will depend both on the quantity and
      nature of the aspirate as well as the individual host response. Aspiration of
      gastric fluids may cause damage to airway epithelium, not only because acidity is
      toxic to bronchial epithelial cells but also due to the effect of digestive
      enzymes such as pepsin and bile salts. Experimental models have shown that direct
      instillation of these factors to airways epithelia cause damage with a
      consequential inflammatory response. The pathophysiology of these responses is
      gradually being dissected, with better understanding of acute gastric aspiration
      injury, a major cause of acute lung injury, providing opportunities for
      therapeutic intervention and potentially, ultimately, improved understanding of
      the chronic airway response to aspiration. Ultimately, clarification of the
      inflammatory pathways which are related to micro-aspiration via pepsin and bile
      acid salts may eventually progress to pharmacological intervention and surgical
      studies to assess the clinical benefits of such therapies in driving symptom
      improvement or reducing disease progression.

PMID- 29456776
TI  - What Percentage of Patients is a Candidate for Unicompartmental Knee Replacement
      at a Chinese Arthroplasty Center?
AB  - Background: Data on indication of Unicompartmental Knee Arthroplasty (UKA) in the
      Asian population are currently not available. The current paper evaluates
      patients undergoing knee replacement at a Chinese Orthopaedic Specialty Hospital
      to report the percentage of patients who meet radiographic and clinical
      indication criteria for UKA. Methods: Over a one-year period 463 consecutive
      patients (515 knees) underwent primary knee replacement surgery. Clinical data
      were recorded and preoperative radiographs were assessed. Patients were
      classified as suitable candidates for UKA based on the degree of deformity,
      preoperative ROM and radiographic appearance of osteoarthritis. The different
      indication criteria for body weight and extend of patellofemoral osteoarthritis
      as reported by Kozinn and Scott as well as the Oxford Group were applied.
      Results: 160 knees (31%) were excluded because of inflammatory and posttraumatic
      arthritis. 55 knees had to be excluded because of incomplete radiographs. Of the
      remaining 300 knees with osteoarthritis, 241 knees were excluded because of
      extend of deformity (n=156), decreased range of motion (n=119), advanced
      patellofemoral arthritis with bone loss (n=11) and AP instability (n=1). Of the
      remaining 63 knees, 54 knees (18%) met the modified Oxford criteria for mobile
      UKA and only 25 knees (8%) met the Scott and Kozinn criteria for fixed UKA.
      Conclusion: The current paper suggests that in comparison to Caucasian
      population, only a smaller percentage of patients at a Chinese Orthopaedic
      Specialty Hospital meet the indication criteria for UKA. Therefore, it might make
      sense to concentrate UKA surgeries in high volume centers.

PMID- 29456775
TI  - Interethnic Variations and Clinical Features of Spondyloarthropathies in a Middle
      Eastern Country.
AB  - Objectives: The study aimed to demonstrate the interethnic differences and
      clinical features of Spondyloarthropathy(SpA) patients in a diverse Middle
      Eastern Country. Methods: A retrospective review of medical records to collect
      the required data was conducted for SpA patients at two study institutions in the
      United Arab Emirates. Results: Of 141 SpA patients found, 88 AS(Ankylosing
      Spondylitis) patients and 53 'other SpA' patients were identified. Males
      constituted 81% of AS and 55% of 'other SpA' patients. Patients with AS and
      'other SpA' had a mean age of symptom onset of 28 and 34 years, respectively.49%
      and 40% of AS and 'other SpA' patients had a history of Anti-TNF therapy usage.
      Enthesitis and Uveitis were noted in 16% and 18% of AS patients whilst 53% and
      11% in 'other SpA' patients, respectively.Caucasian, Indian Subcontinent and
      Arabs constituted 93% of our cohort. Mean age of onset of symptoms in the Indian
      Subcontinent 'other SpA' group was much greater than the other two ethnicities.
      Duration of symptoms to diagnosis was 3.5 and 4 years in AS and other SpA
      patients' respectively. HLA-B27 positivity was found in 53%, 80% and 93% of Arab,
      Indian Subcontinent and Caucasian AS patients, respectively, whilst seen in 50%,
      25% and 33% of the same respective ethnicties in 'other SpA' patients.
      Conclusion: This study on 141 patients is the largest to analyse inter-ethnic
      variations in SpA patients in the region. Our cohort shows a short delay in
      diagnosis with a relatively higher Anti-TNF usage.

PMID- 29456777
TI  - Toe Gap Force is Related to Ultrasonic Parameter of Calcaneus Bone Status in
      General Population.
AB  - Background: Elucidating the relation between bone health condition and muscle
      strength can provide useful knowledge for Japan's super-aged society. This study
      ascertained the Speed Of Sound (SOS) of the calcaneus and upper and lower limb
      muscle strength in a general population. Methods: Medical examinations were
      conducted of 277 adult residents (100 men, 177 women; average age 67.1 years) of
      a mountain village. Bilateral hand grip and hand key pinch strength were
      measured. Hip abductor muscle strength was measured using a hand-held
      dynamometer. The pressure between the hallux and second toe (toe-gap force) was
      measured using a toe pressure measuring instrument. The Speed Of Sound (SOS) of
      the calcaneus was assessed using an ultrasound bone densitometer. Stepwise linear
      regression was used to identify the predictor of SOS using several factors as
      explanatory variables: gender, age, height, weight BMI, grip and key pinch power
      strength, hip abductor muscle strength, and toe-gap force in bilateral side. P
      values of < .05 were inferred as statistically significant. Results: Significant
      positive correlation was found between the SOS and each of bilateral hand grip
      and hand key pinch strength, hip abductor muscle strength, and toe-gap force in
      all participants. Stepwise logistic regression revealed gender (beta coefficient=
      -0.32, p= .0001), age (beta coefficient=-0.53, p= .000), height (beta
      coefficient= -0.19, p= .03), and right toe-gap force (beta coefficient= 0.11, p=
      .027) as predictors of calcaneal SOS for all participants. Conclusion: Toe-gap
      force assessment might be more useful to predict calcaneal SOS than grip
      assessment in the general population.

PMID- 29456778
TI  - Incidence and Functional Outcomes of Scapholunate Diastases Associated Distal
      Radius Fractures: A 2-year Follow-Up Scapholunate Dissociation.
AB  - Background: The Scapholunate Interosseous Ligament (SLIL) is the first intrinsic
      carpal ligament to be injured in wrist trauma, present in up to 64% of the distal
      radius fractures. However, it remains unclear what patients develop symptoms,
      making primary treatment of these injuries accompanying distal radius fractures
      remains questionable. Objective: The aim of this study was to evaluate the
      functional outcomes of patients with scapholunate diastasis associated with
      distal radius fractures. Methods: We evaluated 391 patients with a distal radius
      fracture. Using Computer Tomography (CT) scans the scapholunate interval was
      measured. We identified 14 patients with an SLD (>3mm) of the injured wrist,
      which underwent a CT-scan of the contralateral wrist. To evaluate the functional
      outcomes at a mean follow up of 136+/-90 weeks, we used the Quick Disabilities of
      the Arm, Shoulder and Hand (qDASH) Score. Results: There were 8 patients with
      bilateral SLD and 6 patients with unilateral SLD. Five patients had a qDASH score
      of 0 and one patient showed a qDASH score of 18.2. The patient with a poor score
      had bilateral preexisting osteoarthritis of the wrist. No patient had additional
      surgery of the SLIL. Conclusion: In patients with distal radius fractures, more
      than half of the 14 patients with an SL gap on CT had widening on the
      contralateral side. It is therefore worthwhile to image the contralateral wrist
      before diagnosing a SLD. The patients with unilateral SLD should not be
      surgically treated at initial presentation because they may have good functional
      outcomes after a follow up of 2 years.

PMID- 29456779
TI  - Shared Decision-Making for Nursing Practice: An Integrative Review.
AB  - Background: Shared decision-making has received national and international
      interest by providers, educators, researchers, and policy makers. The literature
      on shared decision-making is extensive, dealing with the individual components of
      shared decision-making rather than a comprehensive process. This view of shared
      decision-making leaves healthcare providers to wonder how to integrate shared
      decision-making into practice. Objective: To understand shared decision-making as
      a comprehensive process from the perspective of the patient and provider in all
      healthcare settings. Methods: An integrative review was conducted applying a
      systematic approach involving a literature search, data evaluation, and data
      analysis. The search included articles from PubMed, CINAHL, the Cochrane Central
      Register of Controlled Trials, and PsycINFO from 1970 through 2016. Articles
      included quantitative experimental and non-experimental designs, qualitative, and
      theoretical articles about shared decision-making between all healthcare
      providers and patients in all healthcare settings. Results: Fifty-two papers were
      included in this integrative review. Three categories emerged from the synthesis:
      (a) communication/ relationship building; (b) working towards a shared decision;
      and (c) action for shared decision-making. Each major theme contained sub-themes
      represented in the proposed visual representation for shared decision-making.
      Conclusion: A comprehensive understanding of shared decision-making between the
      nurse and the patient was identified. A visual representation offers a guide that
      depicts shared decision-making as a process taking place during a healthcare
      encounter with implications for the continuation of shared decisions over time
      offering patients an opportunity to return to the nurse for reconsiderations of
      past shared decisions.

PMID- 29456780
TI  - Attitudes of Jordanian Adolescent Students Toward Overweight and Obesity.
AB  - Background: Obesity is a serious public health problem especially among
      adolescents. Understanding adolescents' attitudes toward obesity and healthy
      lifestyle is a crucial step to develop effective health programs to treat and
      prevent obesity. Objectives: To examine the attitudes toward overweight and
      obesity among Jordanian adolescent students and to identify the components of
      obesity prevention program that the students perceive as important. Methods: A
      sample of 1000 students in 8th to 10th grades was randomly selected from 16
      schools in Irbid, Jordan. A self-reported questionnaire including attitude
      related questions was used in a descriptive, cross-sectional study. Results:
      Generally, the students expressed positive attitudes toward obesity; which means
      that their attitudes were consistent with societal norms in terms of health and
      social functioning (mean= 3.5, SD=0.39). Furthermore, the students expressed
      positive attitudes toward lifestyle; which means that their attitudes were
      consistent with healthy behaviors (mean=3.7, SD=0.58). However, boys had
      significantly more positive attitudes than girls (p=0.04). The prevalence of
      overweight and obesity was 23.8%, while obese and non-obese students had similar
      attitudes toward lifestyle and obesity. Finally, around 20% to 30% of students
      desired a prevention program out of school time shared with their families and
      friends and involves eating healthy food and getting more exercise. Conclusion:
      More efforts are needed to build effective obesity prevention programs that focus
      on eating healthy diet and getting more exercise considering gender differences.

PMID- 29456781
TI  - Functional Magnetic Resonance Imaging of the Domestic Dog: Research, Methodology,
      and Conceptual Issues.
AB  - Neuroimaging of the domestic dog is a rapidly expanding research topic in terms
      of the cognitive domains being investigated. Because dogs have shared both a
      physical and social world with humans for thousands of years, they provide a
      unique and socially relevant means of investigating a variety of shared human and
      canine psychological phenomena. Additionally, their trainability allows for
      neuroimaging to be carried out noninvasively in an awake and unrestrained state.
      In this review, a brief overview of functional magnetic resonance imaging (fMRI)
      is followed by an analysis of recent research with dogs using fMRI.
      Methodological and conceptual concerns found across multiple studies are raised,
      and solutions to these issues are suggested. With the research capabilities
      brought by canine functional imaging, findings may improve our understanding of
      canine cognitive processes, identify neural correlates of behavioral traits, and
      provide early-life selection measures for dogs in working roles.

PMID- 29456782
TI  - Other People's Money: The Role of Reciprocity and Social Uncertainty in Decisions
      for Others.
AB  - Many important decisions are taken not by the person who will ultimately gain or
      lose from the outcome, but on their behalf, by somebody else. We examined
      economic decision-making about risk and time in situations in which deciders
      chose for others who also chose for them. We propose that this unique setting,
      which has not been studied before, elicits perception of reciprocity that prompts
      a unique bias in preferences. We found that decision-makers are less patient
      (more discounting), and more risk averse for losses than gains, with other
      peoples' money, especially when their choices for others are more uncertain.
      Those results were derived by exploiting a computational modeling framework that
      has been shown to account for the underlying psychological and neural decision
      processes. We propose a novel theoretical mechanism-precautionary preferences
      under social uncertainty, which explains the findings. Implications for future
      research and alternative models are also discussed.

PMID- 29456783
TI  - The Role of Stress-Induced O-GlcNAc Protein Modification in the Regulation of
      Membrane Transport.
AB  - O-linked N-acetylglucosamine (O-GlcNAc) is a posttranslational modification that
      is increasingly recognized as a signal transduction mechanism. Unlike other
      glycans, O-GlcNAc is a highly dynamic and reversible process that involves the
      addition and removal of a single N-acetylglucosamine molecule to Ser/Thr residues
      of proteins. UDP-GlcNAc-the direct substrate for O-GlcNAc modification-is
      controlled by the rate of cellular metabolism, and thus O-GlcNAc is dependent on
      substrate availability. Serving as a feedback mechanism, O-GlcNAc influences the
      regulation of insulin signaling and glucose transport. Besides nutrient sensing,
      O-GlcNAc was also implicated in the regulation of various physiological and
      pathophysiological processes. Due to improvements of mass spectrometry
      techniques, more than one thousand proteins were detected to carry the O-GlcNAc
      moiety; many of them are known to participate in the regulation of metabolites,
      ions, or protein transport across biological membranes. Recent studies also
      indicated that O-GlcNAc is involved in stress adaptation; overwhelming evidences
      suggest that O-GlcNAc levels increase upon stress. O-GlcNAc elevation is
      generally considered to be beneficial during stress, although the exact nature of
      its protective effect is not understood. In this review, we summarize the current
      data regarding the oxidative stress-related changes of O-GlcNAc levels and
      discuss the implications related to membrane trafficking.

PMID- 29456784
TI  - Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial
      Redox Environment Deterioration.
AB  - Acrolein is known to be involved in acute lung injury and other pulmonary
      diseases. A number of studies have suggested that acrolein-induced toxic effects
      are associated with depletion of antioxidants, such as reduced glutathione and
      protein thiols, and production of reactive oxygen species. Mitochondrial NADP+
      dependent isocitrate dehydrogenase (idh2) regulates mitochondrial redox balance
      and reduces oxidative stress-induced cell injury via generation of NADPH.
      Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using
      idh2 short hairpin RNA- (shRNA-) transfected Lewis lung carcinoma (LLC) cells and
      idh2-deficient (idh2-/- ) mice. Downregulation of idh2 expression increased
      susceptibility to acrolein via induction of apoptotic cell death due to elevated
      mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced
      lung injury in idh2 knockout mice through the disruption of mitochondrial redox
      status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC
      cells and in idh2 knockout mice was ameliorated by the antioxidant, N
      acetylcysteine, through attenuation of oxidative stress resulting from idh2
      deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox
      environment deterioration, which causes acrolein-mediated apoptosis of LLC cells
      and acrolein-induced lung injury in idh2-/- mice. The present study supports the
      central role of idh2 deficiency in inducing oxidative stress resulting from
      acrolein-induced disruption of mitochondrial redox status in the lung.

PMID- 29456785
TI  - Protein Glutathionylation in the Pathogenesis of Neurodegenerative Diseases.
AB  - Protein glutathionylation is a redox-mediated posttranslational modification that
      regulates the function of target proteins by conjugating glutathione with a
      cysteine thiol group on the target proteins. Protein glutathionylation has
      several biological functions such as regulation of metabolic pathways, calcium
      homeostasis, signal transduction, remodeling of cytoskeleton, inflammation, and
      protein folding. However, the exact role and mechanism of glutathionylation
      during irreversible oxidative stress has not been completely defined.
      Irreversible oxidative damage is implicated in a number of neurological
      disorders. Here, we discuss and highlight the most recent findings and several
      evidences for the association of glutathionylation with neurodegenerative
      diseases and the role of glutathionylation of specific proteins in the
      pathogenesis of neurodegenerative diseases. Understanding the important role of
      glutathionylation in the pathogenesis of neurodegenerative diseases may provide
      insights into novel therapeutic interventions.

PMID- 29456786
TI  - Hederagenin Induces Apoptosis in Cisplatin-Resistant Head and Neck Cancer Cells
      by Inhibiting the Nrf2-ARE Antioxidant Pathway.
AB  - Acquired resistance to cisplatin is the most common reason for the failure of
      cisplatin chemotherapy. Hederagenin, triterpenoids extracted from ivy leaves,
      exhibits antitumor activity in various types of cancer. However, the therapeutic
      potential of hederagenin in head and neck cancer (HNC) has remained unclear.
      Therefore, we examined the effects of hederagenin in cisplatin-resistant HNC
      cells and characterized its molecular mechanisms of action in this context. We
      evaluated the effects of hederagenin treatment on cell viability, apoptosis,
      reactive oxygen species (ROS) production, glutathione levels, mitochondrial
      membrane potential (DeltaPsim), and protein and mRNA expression in HNC cells. The
      antitumor effect of hederagenin in mouse tumor xenograft models was also
      analyzed. Hederagenin selectively induced cell death in both cisplatin-sensitive
      and cisplatin-resistant HNC cells by promoting changes in DeltaPsim and inducing
      apoptosis. Hederagenin inhibited the Nrf2-antioxidant response element (ARE)
      pathway and activated p53 in HNC cells, thereby enhancing ROS production and
      promoting glutathione depletion. These effects were reversed by the antioxidant
      trolox. Hederagenin activated intrinsic apoptotic pathways via cleaved PARP,
      cleaved caspase-3, and Bax. The selective inhibitory effects of hederagenin were
      confirmed in cisplatin-resistant HNC xenograft models. These data suggest that
      hederagenin induces cell death in resistant HNC cells via the Nrf2-ARE
      antioxidant pathway.

PMID- 29456787
TI  - Comparison of Selected Parameters of Redox Homeostasis in Patients with Ataxia
      Telangiectasia and Nijmegen Breakage Syndrome.
AB  - This study compared the antioxidant status and major lipophilic antioxidants in
      patients with ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS).
      Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress
      index (OSI), and concentrations of coenzyme Q10 (CoQ10) and vitamins A and E were
      estimated in the plasma of 22 patients with AT, 12 children with NBS, and the
      healthy controls. In AT patients, TAS (median 261.7 MUmol/L) was statistically
      lower but TOS (496.8 MUmol/L) was significantly elevated in comparison with the
      healthy group (312.7 MUmol/L and 311.2 MUmol/L, resp.). Tocopherol (0.8 MUg/mL)
      and CoQ10 (0.1 MUg/mL) were reduced in AT patients versus control (1.4 MUg/mL and
      0.3 MUg/mL, resp.). NBS patients also displayed statistically lower TAS levels
      (290.3 MUmol/L), while TOS (404.8 MUmol/L) was comparable to the controls. We
      found that in NBS patients retinol concentration (0.1 MUg/mL) was highly elevated
      and CoQ10 (0.1 MUg/mL) was significantly lower in comparison with those in the
      healthy group. Our study confirms disturbances in redox homeostasis in AT and NBS
      patients and indicates a need for diagnosing oxidative stress in those cases as a
      potential disease biomarker. Decreased CoQ10 concentration found in NBS and AT
      indicates a need for possible supplementation.

PMID- 29456789
TI  - Novel Modifications of Glycopeptide Antibiotics via Total Synthesis.
AB  - Although vancomycin has been in clinical use since the late 1950s, resistance due
      to alteration in the target microbe's peptidoglycan can vary significantly,
      reducing its activity. Total synthesis of derivatives has now led to a molecule
      with very significant activity against resistant strains.

PMID- 29456788
TI  - Antroquinonol Exerts Immunosuppressive Effect on CD8+ T Cell Proliferation and
      Activation to Resist Depigmentation Induced by H2O2.
AB  - Antroquinonol was investigated as antioxidant and inhibition of inflammatory
      responses. Our study was to evaluate its immunosuppressive effect on CD8+ T cells
      and protective effect on depigmentation. CD8+ T cells were treated with
      antroquinonol in vitro, and C57BL/6 mice were treated with antroquinonol with or
      without H2O2in vivo for 50 consecutive days. We found antroquinonol could inhibit
      proliferation of CD8+ T cells and suppress the production of cytokines IL-2 and
      IFN-gamma and T cell activation markers CD69 and CD137 in vitro. H2O2 treatment
      induced depigmentation and reduced hair follicle length, skin thickness, and
      tyrosinase expression in vivo. Whereas, antroquinonol obviously ameliorated
      depigmentation of mice skin and resisted the reduction of hair follicle length,
      skin thickness, and tyrosinase expression induced by H2O2. Antroquinonol
      decreased CD8+ T cell infiltration in mice skin, inhibited the production of IL-2
      and IFN-gamma, and decreased the expression of CXCL10 and CXCR3. Summarily, our
      data shows antroquinonol inhibits CD8+ T cell proliferation in vitro. It also
      reduces CD8+ T cell infiltration and proinflammatory cytokine secretion and
      suppresses the thinning of epidermal layer in vivo. Our findings suggest that
      antroquinonol exerts immunosuppressive effects on CD8+ T cell proliferation and
      activation to resist depigmentation induced by H2O2.

PMID- 29456790
TI  - Late-Stage Microsomal Oxidation Reduces Drug-Drug Interaction and Identifies
      Phosphodiesterase 2A Inhibitor PF-06815189.
AB  - Late-stage oxidation using liver microsomes was applied to phosphodiesterase 2
      inhibitor 1 to reduce its clearance by cytochrome P450 enzymes, introduce renal
      clearance, and minimize the risk for victim drug-drug interactions. This approach
      yielded PF-06815189 (2) with improved physicochemical properties and a mixed
      metabolic profile. This example highlights the importance of C-H diversification
      methods to drug discovery.

PMID- 29456791
TI  - Nonacidic Chemotype Possessing N-Acylated Piperidine Moiety as Potent Farnesoid X
      Receptor (FXR) Antagonists.
AB  - Farnesoid X receptor (FXR) plays a major role in the control of cholesterol
      metabolism. Antagonizing transcriptional activity of FXR is an effective means to
      treat the relevant metabolic syndrome. Some of antagonists so far have the
      charged functions; however, they may negatively affect the pharmacokinetics. We
      describe herein a structure-activity relationship (SAR) exploration of nonacidic
      FXR antagonist 6 focusing on two regions in the structure and biological
      evaluation of nonacidic 10 with the characteristic N-acylated piperidine group
      obtained from SAR studies. As the robust affinity to FXR is feasible with our
      nonacidic analogue, 10 is among the most promising candidates for in vivo
      testing.

PMID- 29456792
TI  - N-Leucinyl Benzenesulfonamides as Structurally Simplified Leucyl-tRNA Synthetase
      Inhibitors.
AB  - N-Leucinyl benzenesulfonamides have been discovered as a novel class of potent
      inhibitors of E. coli leucyl-tRNA synthetase. The binding of inhibitors to the
      enzyme was measured by using isothermal titration calorimetry. This provided
      information on enthalpy and entropy contributions to binding, which, together
      with docking studies, were used for structure-activity relationship analysis.
      Enzymatic assays revealed that N-leucinyl benzenesulfonamides display remarkable
      selectivity for E. coli leucyl-tRNA synthetase compared to S. aureus and human
      orthologues. The simplest analogue of the series, N-leucinyl benzenesulfonamide
      (R = H), showed the highest affinity against E. coli leucyl-tRNA synthetase and
      also exhibited antibacterial activity against Gram-negative pathogens (the best
      MIC = 8 MUg/mL, E. coli ATCC 25922), which renders it as a promising template for
      antibacterial drug discovery.

PMID- 29456793
TI  - Synthesis of Novel Tetrahydroisoquinoline CXCR4 Antagonists with Rigidified Side
      Chains.
AB  - A structure-activity relationship study of potent TIQ15-derived CXCR4 antagonists
      is reported. In this investigation, the TIQ15 side-chain was constrained to
      improve its drug properties. The cyclohexylamino congener 15a was found to be a
      potent CXCR4 inhibitor (IC50 = 33 nM in CXCL12-mediated Ca2+ flux) with enhanced
      stability in liver microsomes and reduced inhibition of CYP450 (2D6). The
      improved CXCR4 antagonist 15a has potential therapeutic application as a single
      agent or combinatory anticancer therapy.

PMID- 29456794
TI  - Discovery of 3,3'-Spiro[Azetidine]-2-oxo-indoline Derivatives as Fusion
      Inhibitors for Treatment of RSV Infection.
AB  - A new series of 3,3'-spirocyclic-2-oxo-indoline derivatives was synthesized and
      evaluated against respiratory syncytial virus (RSV) in a cell-based assay and
      animal model. Extensive structure-activity relationship study led to a lead
      compound 14h, which exhibited excellent in vitro potency with an EC50 value of
      0.8 nM and demonstrated 71% oral bioavailability in mice. In a mouse challenge
      model of RVS infection, 14h demonstrated superior efficacy with a 3.9log RSV
      virus load reduction in the lung following an oral dose of 50 mg/kg.

PMID- 29456795
TI  - Discovery of EBI-2511: A Highly Potent and Orally Active EZH2 Inhibitor for the
      Treatment of Non-Hodgkin's Lymphoma.
AB  - A novel series of benzofuran derived EZH2 inhibitors were discovered through a
      scaffold hopping approach based on the clinical compound of EPZ-6438. Further
      rational structure-activity relationship exploration and optimization led to the
      discovery of more potent EZH2 inhibitors with oral bioavailability in mice and
      rats. A lead compound EBI-2511 (compound 34) demonstrated excellent in vivo
      efficacy in Pfeiffer tumor Xenograft models in mouse and is under preclinical
      development for the treatment of cancers associated with EZH2 mutations.

PMID- 29456796
TI  - Discovery of Tetralones as Potent and Selective Inhibitors of Acyl
      CoA:Diacylglycerol Acyltransferase 1.
AB  - Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) plays an important role in
      triglyceride synthesis and is a target of interest for the treatment of metabolic
      disorders. Herein we describe the structure-activity relationship of a novel
      tetralone series of DGAT1 inhibitors and our strategies for overcoming genotoxic
      liability of the anilines embedded in the chemical structures, leading to the
      discovery of a candidate compound, (S)-2-(6-(5-(3-(3,4
      difluorophenyl)ureido)pyrazin-2-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-1,2,3,4
      tetrahydronaphthalen-2-yl)acetic acid (GSK2973980A, 26d). Compound 26d is a
      potent and selective DGAT1 inhibitor with excellent DMPK profiles and in vivo
      efficacy in a postprandial lipid excursion model in mice. Based on the overall
      biological and developability profiles and acceptable safety profiles in the 7
      day toxicity studies in rats and dogs, compound 26d was selected as a candidate
      compound for further development in the treatment of metabolic disorders.

PMID- 29456797
TI  - Using tert-Butyl Groups in a Ligand To Identify Its Binding Site on a Protein.
AB  - Few methods allow determining the binding site of tightly binding ligands. We
      show that ligands containing a tert-butyl (e.g., Boc) group produce easily
      observable nuclear Overhauser effects (NOE) with the target protein even when the
      tert-butyl group is not highly solvent exposed. NOEs with methyl groups of the
      target protein are readily assigned by selectively isotope labeling, presenting a
      practical and quick way to pinpoint the location of the ligand without any prior
      specific nuclear magnetic resonance assignments of the protein. The approach
      works for nonexchanging ligands as well as for weakly binding ligands.

PMID- 29456798
TI  - 18F-Radiolabeled Panobinostat Allows for Positron Emission Tomography Guided
      Delivery of a Histone Deacetylase Inhibitor.
AB  - Histone deacetylase (HDAC) inhibition is becoming an increasingly popular
      approach to treat cancer, as HDAC overexpression is common in many malignancies.
      The blood-brain barrier (BBB) prevents systemically delivered drugs from reaching
      brain at effective concentration, making small-molecule-HDAC inhibition in brain
      tumors particularly challenging. To circumvent the BBB, novel routes for
      administering therapeutics are being considered in the clinic, and a need exists
      for drugs whose deliveries can be directly imaged, so that effective delivery
      across the BBB can be monitored. We report chemistry for radiolabeling the HDAC
      inhibitor, panobinostat, with fluoride-18 (compound-1). Like panobinostat,
      compound 1 retains nanomolar efficacy in diffuse intrinsic pontine glioma (DIPG
      IV and XIII) cells (IC50 = 122 and 108 nM, respectively), with lesser activity
      against U87 glioma. With a favorable therapeutic ratio, 1 is highly selective to
      glioma and demonstrates considerably less toxicity toward healthy astrocyte
      controls (IC50 = 5265 nM). Compound 1 is stable in aqueous solution at
      physiological pH (>7 days, fetal bovine serum), and its delivery can be imaged by
      positron emission tomography (PET). Compound 1 is synthesized in two steps, and
      employs rapid, late-stage aqueous isotopic exchange 18F-radiochemistry. PET is
      used to image the in vivo delivery of [18F]-1 to the murine central nervous
      system via convection enhanced delivery.

PMID- 29456799
TI  - From RORgammat Agonist to Two Types of RORgammat Inverse Agonists.
AB  - Biaryl amides as new RORgammat modulators were discovered. The crystal structure
      of biaryl amide agonist 6 in complex with RORgammat ligand binding domain (LBD)
      was resolved, and both "short" and "long" inverse agonists were obtained by
      removing from 6 or adding to 6 a proper structural moiety. While "short" inverse
      agonist (8) recruits a corepressor peptide and dispels a coactivator peptide,
      "long" inverse agonist (9) dispels both. The two types of inverse agonists can be
      utilized as potential tools to study mechanisms of Th17 transcriptional network
      inhibition and related disease biology.

PMID- 29456800
TI  - Discovery and in Vitro Optimization of 3-Sulfamoylbenzamides as ROMK Inhibitors.
AB  - Inhibitors of the renal outer medullary potassium channel (ROMK) show promise as
      novel mechanism diuretics, with potentially lower risk of diuretic-induced
      hypokalemia relative to current thiazide and loop diuretics. Here, we report the
      identification of a novel series of 3-sulfamoylbenzamide ROMK inhibitors.
      Starting from HTS hit 4, this series was optimized to provide ROMK inhibitors
      with good in vitro potencies and well-balanced ADME profiles. In contrast to
      previously reported small-molecule ROMK inhibitors, members of this series were
      demonstrated to be highly selective for inhibition of human over rat ROMK and to
      be insensitive to the N171D pore mutation that abolishes inhibitory activity of
      previously reported ROMK inhibitors.

PMID- 29456801
TI  - Identification of Potent Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors Based on
      a Phenylimidazole Scaffold.
AB  - Inhibition of indoleamine 2,3-dioxygenase (IDO1) is an attractive
      immunotherapeutic approach for the treatment of a variety of cancers.
      Dysregulation of this enzyme has also been implicated in other disorders
      including Alzheimer's disease and arthritis. Herein, we report the structure
      based design of two related series of molecules: N1-substituted 5
      indoleimidazoles and N1-substituted 5-phenylimidazoles. The latter (and more
      potent) series was accessed through an unexpected rearrangement of an imine
      intermediate during a Van Leusen imidazole synthesis reaction. Evidence for the
      binding modes for both inhibitor series is supported by computational and
      structure-activity relationship studies.

PMID- 29456802
TI  - HTS by NMR for the Identification of Potent and Selective Inhibitors of
      Metalloenzymes.
AB  - We have recently proposed a novel drug discovery approach based on biophysical
      screening of focused positional scanning libraries in which each element of the
      library contained a common binding moiety for the given target or class of
      targets. In this Letter, we report on the implementation of this approach to
      target metal containing proteins. In our implementation, we first derived a
      focused positional scanning combinatorial library of peptide mimetics (of
      approximately 100,000 compounds) in which each element of the library contained
      the metal-chelating moiety hydroxamic acid at the C-terminal. Screening of this
      library by nuclear magnetic resonance spectroscopy in solution allowed the
      identification of a novel and selective compound series targeting MMP-12. The
      data supported that our general approach, perhaps applied using other metal
      chelating agents or other initial binding fragments, may result very effective in
      deriving novel and selective agents against metalloenzyme.

PMID- 29456803
TI  - Potent Inhibitors of Hepatitis C Virus NS3 Protease: Employment of a
      Difluoromethyl Group as a Hydrogen-Bond Donor.
AB  - The design and synthesis of potent, tripeptidic acylsulfonamide inhibitors of HCV
      NS3 protease that contain a difluoromethyl cyclopropyl amino acid at P1 are
      described. A cocrystal structure of 18 with a NS3/4A protease complex suggests
      the presence of a H-bond between the polarized C-H of the CHF2 moiety and the
      backbone carbonyl of Leu135 of the enzyme. Structure-activity relationship
      studies indicate that this H-bond enhances enzyme inhibitory potency by 13- and
      17-fold compared to the CH3 and CF3 analogues, respectively, providing insight
      into the deployment of this unique amino acid.

PMID- 29456804
TI  - Biocompatible Boron-Containing Prodrugs of Belinostat for the Potential Treatment
      of Solid Tumors.
AB  - Despite promising therapeutic utilities for treatment of hematological
      malignancies, histone deacetylase inhibitor (HDACi) drugs have not proven as
      effective in the treatment of solid tumors. To expand the clinical indications of
      HDACi drugs, we developed novel boron-containing prodrugs of belinostat (2), one
      of which efficiently releases active 2 through a cascade of reactions in cell
      culture and demonstrates activities comparable to 2 against a panel of cancer
      cell lines. Importantly, prodrug 7 is more efficacious than belinostat in vivo,
      not only inhibiting the growth of tumor but also reducing tumor volumes in an MCF
      7 xenograft tumor model owing to its superior biocompatibility, which suggests
      its clinical potential in the treatment of solid tumors.

PMID- 29456805
TI  - Click-Addressable Cassette for Photoaffinity Labeling.
AB  - A small molecule 1 was designed to contain an alkyne, a trifluoromethyl
      phenyldiazirine, and a free piperidine-NH for facile conjugation to protein
      binding ligands. This "cassette" 1 was synthesized via a relatively direct route
      involving only routine steps. In this proof-of-concept study, putative ligands
      for carbonic anhydrase IX and for TrkC were conjugated to 1. Photoaffinity
      labeling was performed using purified extracellular regions of both these protein
      receptors, and using cells that express these receptors (isolation via a pull
      down procedure), labeling of the protein was observed in all four experiments.

PMID- 29456806
TI  - Women with hereditary breast cancer predispositions should avoid using their
      smartphones, tablets, and laptops at night.
AB  - Breast cancer is the most common malignancy among women, both in the developed
      and developing countries. Women with mutations in the BRCA1 and BRCA2 genes have
      an increased risk of breast and ovarian cancers. Recent studies show that short
      wavelength visible light disturb the secretion of melatonin and causes circadian
      rhythm disruption. We have previously studied the health effects of exposure to
      different levels of radiofrequency electromagnetic fields (RF-EMFs) such as
      mobile phones, mobile base stations, mobile phone jammers, laptop computers, and
      radars. Moreover, over the past several years, we investigated the health effects
      of exposure to the short wavelength visible light in the blue region emitted from
      digital screens. The reduction of melatonin secretion after exposure to blue
      light emitted from smartphone's screen has been reported to be associated with
      the negative impact of smartphone use at night on sleep. We have shown that both
      the blue light and RF-EMFs generated by mobile phones are linked to the
      disruption of the circadian rhythm in people who use their phones at night.
      Therefore, if women with hereditary breast cancer predispositions use their
      smartphones, tablets and laptops at night, disrupted circadian rhythms
      (suppression of melatonin caused by exposure to blue light emitted from the
      digital screens), amplifies the risk of breast cancer. It can be concluded that
      women who carry mutated BRCA1 or BRCA2, or women with family history of breast
      cancer should avoid using their smartphones, tablets and laptops at night. Using
      sunglasses with amber lenses, or smartphone applications which decrease the
      users' exposure to blue light before sleep, at least to some extent, can decrease
      the risk of circadian rhythm disruption and breast cancer.

PMID- 29456807
TI  - Potential of polymeric particles as future vaccine delivery systems/adjuvants for
      parenteral and non-parenteral immunization against tuberculosis: A systematic
      review.
AB  - Objectives: Production of effective tuberculosis (TB) vaccine is necessity.
      However, the development of new subunit vaccines is faced with concerns about
      their weak immunogenicity. To overcome such problems, polymers-based vaccine
      delivery systems have been proposed to be used via various routes. The purpose of
      this study was to determine the potential of polymeric particles as future
      vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization
      against TB. Materials and Methods: PubMed, Scopus, Science-Direct, and the ISI
      web of knowledge databases were searched for related keywords. A total of 420
      articles, written up to June 25, 2016, were collected on the potential of
      polymeric particles as TB vaccine delivery systems after parenteral and non
      parenteral immunization. Thirty-one relevant articles were selected by applying
      inclusion and exclusion criteria. Results: It was shown that the immunogenicity
      of TB vaccines had been improved by using biodegradable and non-biodegradable
      synthetic polymers as well as natural polymers and they are better able to
      enhance the humoral and cellular immune responses, compared to TB vaccines alone.
      The present study revealed that various polymeric particles, after M.
      tuberculosis challenge in animal models, provide long-lasting protection against
      TB. PLGA (poly (lactide-co-glycolide)) and chitosan polymers were widely used as
      TB vaccine delivery systems/adjuvants. Conclusion: It seems that PLGA and
      chitosan polymers are well-suited particles for the parenteral and non-parenteral
      administration of TB vaccines, respectively. Non-biodegradable synthetic polymers
      in comparison with biodegradable synthetic and natural polymers have been used
      less frequently. Therefore, further study on this category of polymers is
      required.

PMID- 29456808
TI  - Administration of melatonin protects against acetylsalicylic acid-induced
      impairment of male reproductive function in mice.
AB  - Objectives: Melatonin, an important hormone secreted by the epiphysis, is a
      powerful anti-oxidant with a high potential to neutralize medical toxins. The
      goal of this study was to demonstrate the beneficial effect of melatonin on
      epididymal sperm and reproductive parameters in mice treated with acetylsalicylic
      acid (ASA). Materials and Methods: Male adult mice were divided into four
      treatment groups: control, ASA, melatonin, and ASA+melatonin. Mice were
      administered ASA (50 mg/kg, orally) and/or melatonin (10 mg/kg,
      intraperitoneally), or vehicle control, for 14 days. Sperm count, sperm motility,
      and sperm morphology were evaluated to assess fertility. A colorimetric assay was
      used to measure serum total antioxidant capacity (TAC). A sperm chromatin
      dispersion (SCD) test was used to assess sperm chromatin integrity. Sex hormone
      levels were measured by ELISA. Results: Compared to the control group, ASA
      treatment resulted in a significant decrease in sperm parameters (P<0.05), as
      well as a decrease in the integrity of sperm chromatin (P<0.01). ASA treatment
      also reduced serum testosterone and TAC levels (P<0.05). Co-administration of
      melatonin with ASA significantly improved epididymal sperm parameters and
      increased serum testosterone and TAC levels compared to the ASA-treated group. LH
      level was not different in the combined treatment group compared to control or
      ASA treatment. Conclusion: Short-term administration of ASA (50 mg/kg) has
      adverse effects on male reproductive function in mice. Co-administration of
      melatonin protects against ASA-induced impairment of male reproductive function
      by preventing the reduction in serum TAC and testosterone levels seen with ASA
      treatment alone.

PMID- 29456809
TI  - Hypericin-photodynamic therapy inhibits proliferation and induces apoptosis in
      human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A.
AB  - Objectives: To elucidate the effects and potential mechanisms of hypericin
      photodynamic therapy (HYP-PDT) for treating the human rheumatoid arthritis (RA)
      fibroblast-like synoviocyte (FLS) MH7A cell-line. Materials and Methods: MH7A
      cells were subjected to HYP-PDT intervention and apoptosis was evaluated via MTT,
      nuclear staining, and flowcytometry analyses. Intracellular reactive oxygen
      species (ROS) were measured with the fluorescent probe 2'7'-dichlorofluorescein
      diacetate (DCFH-DA). To verify the effects of HYP on apoptotic and nuclear factor
      kappa-B (NF-kappaB) pathways, caspase-8, 9, poly-ADP-ribose polymerase (PARP),
      phosphorylated (p)-NF-kappaB p65, NF-kappaB p65 and p-IkappaBalpha protein
      expressions were quantified with Western blot. Quantitative real-time PCR was
      used to assay NF-kappaB p65 mRNA. Results: HYP-PDT inhibited MH7A cell viability
      and induced apoptosis in a dose-dependent manner. Meanwhile, intracellular ROS
      levels increased significantly after HYP-PDT treatment. Furthermore, the
      expression of cleaved caspase-9 and PARP was increased by HYP-PDT treatment, with
      a concurrent decline in NF-kappaB. Conclusion: HYP-PDT induces apoptosis in MH7A
      cells, at least partially, via generation of ROS, regulation of the apoptotic
      pathway and suppression of the NF-kappaB pathway. These findings suggest that HYP
      PDT may be a potential treatment for RA.

PMID- 29456810
TI  - Minocycline through attenuation of oxidative stress and inflammatory response
      reduces the neuropathic pain in a rat model of chronic constriction injury.
AB  - Objectives: Several lines of evidence showed that minocycline possesses
      antioxidant and anti-inflammatory properties. This study aimed to demonstrate the
      effects of minocycline in rats subjected to chronic constriction injury (CCI).
      Materials and Methods: In this study four groups (n = 6-8) of rats were used as
      follows: Sham, CCI, CCI + minocycline (MIN) 10 mg/Kg (IP) and CCI + MIN 30 mg/Kg
      (IP). On days 3, 7, 14, and 21 post-surgery hot-plate, acetone, and von Frey
      tests were carried out. Finally, Motor Nerve Conduction Velocity Evaluation
      (MNCV) assessment was performed and spinal cords were harvested in order to
      measure tissue concentrations of TNF_alpha, IL-1beta, Glutathione peroxidase
      (GPx), Superoxide dismutase (SOD) and Malondialdehyde (MDA). Extent of perineural
      inflammation and damage around the sciatic nerve was histopathologically
      evaluated. Results: Our results demonstrated that CCI significantly caused
      hyperalgesia and allodynia twenty-one days after CCI. MIN attenuated heat
      hyperalgesia, cold and mechanical allodynia and MNCV in animals. MIN also
      decreased the levels of TNF_alpha and IL-1beta. Antioxidative enzymes (SOD, MDA,
      and GPx) were restored following MIN treatment. Our findings showed that MIN
      decreased perineural inflammation around the sciatic nerve. According to the
      results, the neuropathic pain reduced in the CCI hyperalgesia model using 30
      mg/kg of minocycline. Conclusion: It is suggested that antinociceptive effects of
      minocycline might be mediated through the inhibition of inflammatory response and
      attenuation of oxidative stress.

PMID- 29456811
TI  - In vivo activity assessment of some Tanacetum species used as traditional wound
      healer along with identification of the phytochemical profile by a new validated
      HPLC method.
AB  - Objectives: Tanacetum species are traditionally used as insecticide, and
      externally wound healer as well as for anti-inflammatory and antihistaminic
      properties. The in vivo wound-healing and anti-inflammatory potential of four
      Tanacetum species, Tanacetum argenteum (Lam.) Willd. subsp. argenteum (TA),
      Tanacetum heterotomum (Bornm.) Grierson (TH), Tanacetum densum (Lab.) Schultz
      Bip. subsp. sivasicum (TD), and Tanacetum vulgare L. (TV) was investigated.
      Materials and Methods: The chloroform (CHCl3) and methanol:water (80:20) extracts
      were prepared from the aerial parts of each plant. For assessment of the wound
      healing activity, linear incision on rats and circular excision on mice wound
      models were used and histopathological analyses were conducted on the tissues
      treated with the test materials. For the evaluation of the anti-inflammatory
      activity, Whittle Method based on the inhibition of the acetic acid-induced
      increase in capillary permeability was used. In order to elucidate the
      phytochemical contents of the extracts, HPLC profiles of active fractions were
      screened and quantitative analysis was conducted within the scope of HPLC
      analysis. Results: The CHCl3 extracts of TD, TA and TV were found to have
      significant wound healing activity (37.1%, 30.8% and 26.1% tensile strength;
      88.05%, 72.93% and 44.88% contraction values, respectively) and anti-inflammatory
      activities (31.5% and 26.6% inhibition values for TD and TA). Parthenolide
      content of the CHCl3 extracts of TA, TH and TV were found 242.66+/-1.53, 190.16+/
      5.62 and 177.51+/-3.73 ug/100 mg plant material, respectively. Conclusion:
      According to the results, the other secondary metabolites present in the aerial
      parts of the Tanacetum species possibly exerted synergistic effects on the
      observed healing of the wounds.

PMID- 29456812
TI  - Preparation and evaluation of PCL-PEG-PCL micelles as potential nanocarriers for
      ocular delivery of dexamethasone.
AB  - Objectives: Micelles have been studied as nanoparticulate drug delivery systems
      for improving the topical ocular delivery of hydrophobic drugs. The objective of
      this study was to develop and characterize dexamethasone-loaded polycaprolactone
      polyethylene glycol-polycaprolactone (PCL-PEG-PCL) micelles to improve patient
      compliance and enhance the ocular bioavailability of poorly water-soluble drugs.
      Materials and Methods: The PCL-PEG-PCL copolymers were synthesized via the ring
      opening polymerization of epsilon-caprolactone in the presence of PEG. The
      resulting purified copolymers were characterized by GPC, NMR, FTIR, XRD and DSC.
      The critical micelle concentrations (CMCs) of the mentioned copolymers were
      determined. Dexamethasone was loaded into polymeric micelles by film hydration
      method, and dexamethasone-loaded micelles were characterized by TEM and DLS. Drug
      release kinetics and ex vivo corneal permeability were also determined. Results:
      The CMC of the synthetized copolymers was approximately 0.03 mg/ml. Aqueous
      solutions of the resulting copolymers (400 mg/ml) rapidly formed a gel in situ at
      34 degrees C. The TEM results exhibited the successful formation of spherical
      micelles. The size of the prepared micelles was approximately 40 nm. Formulated
      micelles sustained the release of the incorporated dexamethasone for 5 days.
      Conclusion: Data from ex vivo permeability tests indicated that PCL-PEG-PCL
      micelles can be suitable candidates for the ocular delivery of dexamethasone and,
      likely, other hydrophobic drugs.

PMID- 29456813
TI  - Evaluation of TNF-alpha and IL-6 mRNAs expressions in visceral and subcutaneous
      adipose tissues of polycystic ovarian rats and effects of resveratrol.
AB  - Objectives: Some studies suggest that chronic low-grade inflammation is involved
      in insulin resistance in polycystic ovary syndrome (PCOS). This study assessed
      possible involvement of alteration in expression of two pro-inflammatory factors,
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in adipose
      tissues of PCOS rats in the impairment of insulin actions. Also, effects of
      resveratrol as an anti-inflammatory agent were investigated. Materials and
      Methods: Fifteen female Wistar rats (21 days old) were divided into three groups
      (n=5): I) Control, II) PCO-model-saline: served as PCOS rats and to induce PCOS,
      received subcutaneously testosterone enanthate 1 mg/100 g body weight
      subcutaneously for 35 days, III) PCO-model-resveratrol, after receiving
      testosterone, received resveratrol 10 mg/kg intraperitoneally for 28 days. The
      expression of Tnf-alpha and Il-6 mRNAs in adipose tissues was determined by the
      qRT-PCR method. Results: The Il-6 mRNA expression in the visceral adipose tissue
      of PCOS rats was increased in comparison to controls (P<0.05). Tnf-alpha and Il-6
      mRNA expression in visceral and subcutaneous adipose tissues of polycystic
      ovarian rats was similar to controls. The expression of Tnf-alpha mRNA in
      subcutaneous adipose tissue and Tnf-alpha and Il-6 mRNAs in the visceral adipose
      tissue of the PCO-model-resveratrol group were lower than PCOS rats (P<0.05).
      Conclusion: Increased expression of Il-6 mRNA in the visceral adipose tissue of
      polycystic ovarian rats may be one cause of insulin resistance observed in them
      and resveratrol as an anti-inflammatory and anti-hyperglycemic agent may decrease
      the risk of diabetes by reduction of expression of pro-inflammatory cytokines TNF
      alpha and IL-6 in PCOS patients.

PMID- 29456814
TI  - Ascorbic acid augments colony spreading by reducing biofilm formation of
      methicillin-resistant Staphylococcus aureus.
AB  - Objectives: Staphylococcus aureus is a Gram-positive pathogen, well known for its
      resistance and versatile lifestyle. Under unfavourable conditions, it adapts
      biofilm mode of growth. For staphylococcal biofilm formation, production of
      extracellular polymeric substances (EPS) is a pre-requisite, which is regulated
      by ica operon-encoded enzymes. This study was designed to know the impact of
      ascorbic acid on biofilm formation and colony spreading processes of S. aureus
      and MRSA. Materials and Methods: The isolates of methicillin-resistant S. aureus
      (MRSA) used in present study, were recovered from different food samples. Various
      selective and differential media were used for identification and confirmation of
      S. aureus. Agar dilution method was used for determination of oxacillin and
      ascorbic acid resistance level. MRSA isolates were re-confirmed by E-test and by
      amplification of mecA gene. Tube methods and Congo-Red agar were used to study
      biofilm formation processes. Gene expression studies were carried on real-time
      reverse transcriptase-polymerase chain reaction (RT-PCR). Results: The results
      revealed the presence of mecA gene belonging to SCCmecA type IV along with agr
      type II in the isolates. In vitro studies showed the sub-inhibitory concentration
      of oxacillin induced biofilm production. However, addition of sub-inhibitory dose
      of ascorbic acid was found to inhibit EPS production, biofilm formation and
      augment colony spreading on soft agar plates. The inhibition of biofilm formation
      and augmentation of colony spreading observed with ascorbic acid alone or in
      combination with oxacillin. Moreover, gene expression studies showed that
      ascorbic acid increases agr expression and decreases icaA gene expression.
      Conclusion: The present study concluded that ascorbic acid inhibits biofilm
      formation, promotes colony spreading and increases agr gene expression in MRSA.

PMID- 29456815
TI  - CRISPR/Cas9, a new approach to successful knockdown of ABCB1/P-glycoprotein and
      reversal of chemosensitivity in human epithelial ovarian cancer cell line.
AB  - Objectives: Multidrug resistance (MDR) is a major obstacle in the successful
      chemotherapy of ovarian cancer. Inhibition of P-glycoprotein (P-gp), a member of
      ATP-binding cassette (ABC) transporters, is a well-known strategy to overcome MDR
      in cancer. The aim of this study was to investigate the efficiency and ability of
      CRISPR/Cas9 genome editing technology to knockdown ABCB1 gene expression in
      adriamycin resistant (A2780/ADR) ovarian cancer cell line and evaluate the
      sensitivity changes to doxorubicin. Materials and Methods: Three single-guide
      RNAs (sgRNAs) targeting the fourth and fifth exons of human ABCB1 gene were
      designed in this study. Expression level of ABCB1 was detected using quantitative
      real time PCR (qRT-PCR) after co-transfection of all three sgRNAs into A2780/ADR
      cell line and subsequent antibiotic selection. Drug sensitivity to doxorubicin
      was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. Results: The results showed that CRISPR/Cas9 system could
      significantly reduce the expression of P-gp. The dramatic decline in ABCB1 gene
      expression was associated with increased sensitivity of cells transfected with
      sgRNAs to doxorubicin. Conclusion: Based on the results of this study, it is
      concluded that the CRISPR-based systems, used in the present study, effectively
      down-regulated the target gene and acted as an ideal and cost-effective tool for
      gene editing of A2780/ADR cell line resulting in restoration of nonmalignant
      phenotype.

PMID- 29456816
TI  - Anti-inflammatory activity and chemical composition of Pycnocycla bashagardiana
      fruit's essential oil in animal models.
AB  - Objectives: Pycnocycla bashagardiana is an endemic species found only in Iran.
      Due to the presence of myristicin as the major component of the fruit's oil we
      were prompted to assess the antinociceptive and anti-inflammatory properties of
      P. bashagardiana fruit's essential oil (PBFEO). Materials and Methods: The
      analgesic activities of PBFEO (100, 200, and 400 mg/kg, IP) were studied by hot
      plate and formalin tests in mice. Control and standard groups received vehicle
      and morphine (5 mg/kg, IP), respectively. The acute anti-inflammatory effect of
      PBFEO (200 and 400 mg/kg, IP) were assessed by carrageenan-induced paw edema
      method in 30 min, 1, 2, 3, and 4 hr after carrageenan injection and the chronic
      anti-inflammatory effect of PBFEO (50 and 100 mg/kg, IP) were assessed by the
      cotton pellet-induced granuloma method in rats. Results: In hot-plate and
      formalin tests, the studied doses of PBFEO were not effective. However, in
      carrageenan test, all studied doses of PBFEO significantly reduced the paw edema
      in comparison to the control animals (P<0.05). Anti-inflammatory activity of
      PBFEO (200 and 400 mg/kg, P<0.05) was found to be more than mefenamic acid (30
      mg/kg). In cotton pellet-induced granuloma, PBFEO was also effective regarding
      the transudate and granuloma formation amount. PBFEO was analyzed by gas
      chromatography-mass spectrometry and 12 constituents, representing 96.0% of the
      oil, were identified. The major component of the oil was characterized as
      myristicin which might be responsible for the anti-inflammatory activity.
      Conclusion: The results suggest that PBFEO possesses biologically active
      constituents that have significant peripheral anti-inflammatory effects.

PMID- 29456817
TI  - S100A9 aggravates bleomycin-induced dermal fibrosis in mice via activation of
      ERK1/2 MAPK and NF-kappaB pathways.
AB  - Objectives: This study aims to investigate the pathogenicity and possible
      mechanisms of S100A9 function in mice models of scleroderma. Materials and
      Methods: The content of S100A9 in the skin tissues of mice with scleroderma was
      determined. Different concentrations of bleomycin (BLM) and S100A9 were
      subcutaneously injected into the backs of mice simultaneously, and then
      pathological changes in the skin of these mice were monitored. Specifically, the
      levels of inflammatory cytokines and alpha smooth muscle actin (alpha-SMA), the
      activation of extracellular regulated kinase 1/2 (ERK1/2), mitogen-activated
      protein kinase (MAPK) and nuclear factor-kappa B (NF-kappaB) pathways, and the
      expression of the receptor for advanced glycation end-product (RAGE) in the skin
      were determined. Results: The content of S100A9 in the skin tissues of mice with
      scleroderma was determined. Different concentrations of BLM and S100A9 were
      subcutaneously injected into the backs of mice simultaneously, and then
      pathological changes in the skin of these mice were monitored. Specifically, the
      levels of inflammatory cytokines and alpha smooth muscle actin (alpha-SMA), the
      activation of extracellular regulated kinase 1/2 (ERK1/2) mitogen-activated
      protein kinase (MAPK) and nuclear factor-kappa B (NF-kappaB) pathways, and the
      expression of the receptor for advanced glycation end-product (RAGE) in the skin
      were determined. Conclusion: S100A9 aggravates dermal fibrosis in BLM-induced
      scleroderma (BIS) mice, and its mechanisms might be mediated by RAGE, ERK1/2, and
      NF-kappaB pathway.

PMID- 29456818
TI  - Synthesis and antiplasmodial activity of novel phenanthroline derivatives: An in
      vivo study.
AB  - Objectives: Due to the rapid increased drug resistance to Plasmodium parasites,
      an urgent need to achieve new antiplasmodial drugs is felt. Therefore, in this
      study, the new synthetic phenanthroline derivatives were synthesized with
      antiplasmodial activity. Materials and Methods: A series of 1,10-phenanthroline
      derivatives containing amino-alcohol and amino-ether substituents were
      synthesized via facile procedures, starting with 5,6-epoxy-1,10-phenanthroline.
      Their antiplasmodial activity was then evaluated using Peter's 4-day suppressive
      test against Plasmodium berghei-infected mice (ANKA strain). Furthermore, the
      mean survival time of the mice treated with synthetic compounds was compared with
      the negative control group. Results: The results demonstrated that the compounds
      6-(3-(dibutylamino)propylamino)-5,6-dihydro-1,10-phenanthroline-5-ol(7b) at the
      dose of 150 mg/kg/day and 4-(1,10-phenanthroline-5-yloxy)-N, N-dipropylbutan-1
      amine (8b) at the dose of 15 mg/kg/day have 90.58% and 88.32% suppression,
      respectively. All synthetic compounds prolonged the mean survival time of treated
      mice in comparison with negative control groups, indicating the in vivo
      antiplasmodial activity of these new compounds. Conclusion: The present study is
      the first attempt to achieve new, effective synthetic compounds based on
      phenanthroline scaffold with the antiplasmodial activity. However, more research
      is needed to optimize their antimalarial activity.

PMID- 29456819
TI  - Comparison of the efficacy of piascledine and transforming growth factor beta1 on
      chondrogenic differentiation of human adipose-derived stem cells in fibrin and
      fibrin-alginate scaffolds.
AB  - Objectives: The aim of this study was to compare the chondrogenic induction
      potential of Piascledine and TGF-beta1 on adipose-derived stem cells (ADSCs) in
      fibrin and fibrin-alginate scaffolds. Materials and Methods: Human subcutaneous
      adipose tissues were harvested from three patients who were scheduled to undergo
      liposuction. Isolated ADSCs were proliferated in a culture medium. Then, the
      cells were seeded in fibrin or fibrin-alginate scaffolds and cultured for 14 days
      in a chondrogenic medium containing Piascledine, TGF-beta1, or both. The rate of
      cell proliferation and survival was evaluated by using MTT [3-(4, 5
      dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide] assay and the rate of the
      expression of type II collagen, aggrecan, and type X collagen genes was evaluated
      by real-time polymerase chain reaction (real-time PCR) method. Results: The MTT
      results showed that Piascledine is able to enhance the proliferation and survival
      of ADSCs in fibrin scaffolds in comparison to other groups (P<0.05). Real-time
      PCR evaluation revealed that the expression of type II collagen was higher in TGF
      beta1groups, but the expression of aggrecan was higher in TGF-beta1 alone or
      along with Piascledine in fibrin-alginate scaffolds. Furthermore, the expression
      of type X collagen was lower in Piascledine alone or along with TGF-beta1 in
      fibrin scaffold. Conclusion: Piascledine can enhance the proliferation and
      differentiation of ADSCs in fibrin scaffolds.

PMID- 29456820
TI  - Immunogenicity of heparin-binding hemagglutinin expressed by Pichia pastoris
      GS115 strain.
AB  - Objectives: Heparin-binding hemagglutinin (HBHA), a mycobacterial cell surface
      protein, mediates adhesion to nonphagocytic cells and the dissemination of
      Mycobacterium tuberculosis (M. tuberculosis) from the site of primary infection.
      Superior expression systems are required to obtain abundant M. tuberculosis
      proteins for the purpose of diagnosing M. tuberculosis infection or for the
      immunization. Here, HBHA was expressed by Pichia pastoris (P. pastoris) GS115
      strain , and the immunogenicity of HBHA was evaluated. Materials and Methods: The
      HBHA gene of M. tuberculosis was cloned into the pPIC9K plasmid, which was good
      for electroporation into P. pastoris GS115 strain. Unlabeled HBHA protein was
      purified using a Sepharose CL-6B column, and its expression was confirmed using
      anti-HBHA polyclonal antibody from mouse serum. We injected C57BL/6 mice with
      HBHA/ dimethyldioctadecylammonium/trehalose 6,6'-dibehenate (HBHA/DDA/TDB) to
      investigate the immunogenicity of this potential vaccine. Results: The results
      demonstrated that HBHA/DDA/TDB has the ability to induce high levels of HBHA
      specific IgG antibody and its subclasses, as well as interferon-gamma, compared
      with injection of phosphate-buffered saline, DDA/TDB alone and Bacillus Calmette
      Guerin (BCG) controls (P<0.05). Moreover, the ratio of IgG2a/IgG1 of the
      HBHA/DDA/TDB group was higher than that of the BCG group (P<0.05). Conclusion:
      HBHA with no label has excellent immunogenicity, and is suitable for evaluating
      the effectiveness to prevent M. tuberculosis infection.

PMID- 29456821
TI  - Resveratrol decreases apoptosis and NLRP3 complex expressions in experimental
      varicocele rat model.
AB  - Objectives: Varicocele is an abnormal dilation in the testicular vein, which can
      cause hypoxia, reactive oxygen species accumulation, elevation in testicular
      temperature, and promote apoptosis and increase proinflammatory cytokine
      production. According to the varicocele pathophysiology, it is possible that a
      group of cytosolic receptors called nucleotide oligomerization domain (NOD)-like
      receptor family pyrin domain containing 3 (NLRP3) inflammasomes also involve in
      varicocele pathogenesis. Due to the important role of antioxidant in decreasing
      the testis tissue damage, in this study we investigated the protective effect of
      resveratrol (RES) on NLRP3 complex and apoptosis in experimental varicocele rats.
      Materials and Methods: In this study, 40 male Wistar rats were randomly divided
      into 5 groups (8 rats in each group): Control, experimental left varicocele
      (ELV), ELV + ethanol, ELV + 20 mg/kg RES and ELV + 50 mg/kg RES. Varicocele was
      induced by partial ligation of the left renal vein. Three months after varicocele
      induction, RESwas orally administered to rats for 1 month. The expression levels
      of NLRP3, apoptosis associated speck-like protein (ASC), caspase-1, Bax and Bcl2
      were analyzed using real time PCR. Results: Our results showed that RESat both
      doses significantly (P<= 0.05) decreased the gene expression levels of ASC,
      NLRP3, caspase-1 and Bax and increased Bcl2 gene expression at high dose.
      Conclusions: RESby reducing inflammatory factors and decreasing apoptosis might
      be used as adjuvant therapy to reduce varicocele complication.

PMID- 29456822
TI  - Self-ear cleaning practices and the associated risk of ear injuries and ear
      related symptoms in a group of university students.
AB  - Self-ear cleaning is the insertion of objects into the ear canal to clean it, a
      widespread practice that has the potential to compromise its integrity as a
      natural, selfcleansing mechanism, and a risk factor for possible injuries. The
      practice is common among young adults and highest in university than any other
      graduates. This study aimed to determine the self-ear cleaning practices and
      associated risk of injury and related symptoms in undergraduate students at
      KwaZulu-Natal University. The descriptive survey utilized a self-administered
      questionnaire. Of the 206 participants that responded, 98% engaged in self-ear
      cleaning, with 75% indicating that it was beneficial. The commonest method
      (79.6%) being the use of cotton buds, with an associated injury rate of 2.4%.
      There was no statistically significant associations between those who used or did
      not use cotton buds and the symptoms experienced. The complications indicate that
      self-ear cleaning does pose a risk for injury, necessitating more community
      information and education.

PMID- 29456823
TI  - Health hazards related to Soba sewage treatment plant, Sudan.
AB  - The aim of this study was to determine the health hazards acquired by the
      residents nearby Soba sewage treatment plant. A descriptive cross-sectional study
      was carried out in Soba locality, Khartoum, Sudan. An interviewer-administrated
      questionnaire was assigned to 462 residents of the area living in four
      geographically distributed squares around the sewage plant. The data was analyzed
      in SPSS; Cronbach's alpha reliability scale of measurement was used to check the
      internal validity of six variables related to the quality of life. A logistic
      regression analysis was used to assess the relationship between the health
      hazards and the quality of life. Among the 462 residents, difficulty in breathing
      (37.9%) and nausea (37.2) were the principal health hazards. Moreover, the
      residents had a satisfactory level of awareness (88.7%) about the health hazards.
      The utmost impact on the quality of life was psychological (97.2%). It was
      statistically correlated with the reported factors, which impacted the quality of
      life in the district as revealed by the Cronbach's alpha reliability test with
      absenteeism (P=0.026), disability (P=0.014), socialization (P=0.032) and death
      (P=0.016). A logistic regression analysis revealed chemical hazards had a
      statistically significant association (P<0.05) with quality of life of the
      residents of Soba district. The study strongly entails the fact that sewage
      treatment plants crave exceptional consideration from the concerned responsible
      authorities, together with the fact that the evolved health threats should be
      confronted with immense responsibility as soon as possible.

PMID- 29456825
TI  - Multi-stakeholder perspectives on access, availability and utilization of
      emergency obstetric care services in Lagos, Nigeria: A mixed-methods study.
AB  - Globally, Nigeria is the second most unsafe country to be pregnant, with Lagos,
      its economic nerve center having disproportionately higher maternal deaths than
      the national average. Emergency obstetric care (EmOC) is effective in reducing
      pregnancyrelated morbidities and mortalities. This mixed-methods study
      quantitatively assessed women's satisfaction with EmOC received and qualitatively
      engaged multiple key stakeholders to better understand issues around EmOC access,
      availability and utilization in Lagos. Qualitative interviews revealed that
      regarding access, while government opined that EmOC facilities have been
      strategically built across Lagos, women flagged issues with difficulty in access,
      compounded by perceived high EmOC cost. For availability, though health workers
      were judged competent, they appeared insufficient, overworked and felt poorly
      remunerated. Infrastructure was considered inadequate and paucity of blood and
      blood products remained commonplace. Although pregnant women positively rated the
      clinical aspects of care, as confirmed by the survey, satisfaction gaps remained
      in the areas of service delivery, care organization and responsiveness. These
      areas of discordance offer insight to opportunities for improvements, which would
      ensure that every woman can access and use quality EmOC that is sufficiently
      available.

PMID- 29456826
TI  - Seroprevalence of Ebola virus infection in Bombali District, Sierra Leone.
AB  - A serosurvey of anti-Ebola Zaire virus nucleoprotein IgG prevalence was carried
      out among Ebola virus disease survivors and their Community Contacts in Bombali
      District, Sierra Leone. Our data suggest that the specie of Ebola virus (Zaire)
      responsible of the 2013-2016 epidemic in West Africa may cause mild or
      asymptomatic infection in a proportion of cases, possibly due to an efficient
      immune response.

PMID- 29456824
TI  - A brief review on features of falciparum malaria during pregnancy.
AB  - Malaria in pregnancy is a serious public health problem in tropical areas.
      Frequently, the placenta is infected by accumulation of Plasmodium falciparum
      infected erythrocytes in the intervillous space. Falciparum malaria acts during
      pregnancy by a range of mechanisms, and chronic or repeated infection and co
      infections have insidious effects. The susceptibility of pregnant women to
      malaria is due to both immunological and humoral changes. Until a malaria vaccine
      becomes available, the deleterious effects of malaria in pregnancy can be avoided
      by protection against infection and prompt treatment with safe, effective
      antimalarial agents; however, concurrent infections such as with HIV and
      helminths during pregnancy are jeopardizing malaria control in sub-Saharan
      Africa.

PMID- 29456827
TI  - Impairment of social behaviors in Arhgef10 knockout mice.
AB  - Background: Impaired social interaction is one of the essential features of
      autism spectrum disorder (ASD). Our previous copy number variation (CNV) study
      discovered a novel deleted region associated with ASD. One of the genes included
      in the deleted region is ARHGEF10. A missense mutation of ARHGEF10 has been
      reported to be one of the contributing factors in several diseases of the central
      nervous system. However, the relationship between the loss of ARHGEF10 and the
      clinical symptoms of ASD is unclear. Methods: We generated Arhgef10 knockout mice
      as a model of ASD and characterized the social behavior and the biochemical
      changes in the brains of the knockout mice. Results: Compared with their wild
      type littermates, the Arhgef10-depleted mice showed social interaction
      impairment, hyperactivity, and decreased depression-like and anxiety-like
      behavior. Behavioral measures of learning in the Morris water maze were not
      affected by Arhgef10 deficiency. Moreover, neurotransmitters including serotonin,
      norepinephrine, and dopamine were significantly increased in different brain
      regions of the Arhgef10 knockout mice. In addition, monoamine oxidase A (MAO-A)
      decreased in several brain regions. Conclusions: These results suggest that
      ARHGEF10 is a candidate risk gene for ASD and that the Arhgef10 knockout model
      could be a tool for studying the mechanisms of neurotransmission in ASD. Trial
      registration: Animal studies were approved by the Institutional Animal Care and
      Use Committee of National Taiwan University (IACUC 20150023). Registered 1 August
      2015.

PMID- 29456828
TI  - Theoretical models of inhibitory activity for inhibitors of protein-protein
      interactions: targeting menin-mixed lineage leukemia with small molecules.
AB  - Development and binding affinity predictions of inhibitors targeting protein
      protein interactions (PPI) still represent a major challenge in drug discovery
      efforts. This work reports application of a predictive non-empirical model of
      inhibitory activity for PPI inhibitors, exemplified here for small molecules
      targeting the menin-mixed lineage leukemia (MLL) interaction. Systematic ab
      initio analysis of menin-inhibitor complexes was performed, revealing the
      physical nature of these interactions. Notably, the non-empirical protein-ligand
      interaction energy comprising electrostatic multipole and approximate dispersion
      terms (E(10)El,MTP + EDas) produced a remarkable correlation with experimentally
      measured inhibitory activities and enabled accurate activity prediction for new
      menin-MLL inhibitors. Importantly, this relatively simple and computationally
      affordable non-empirical interaction energy model outperformed binding affinity
      predictions derived from commonly used empirical scoring functions. This study
      demonstrates high relevance of the non-empirical model we developed for binding
      affinity prediction of inhibitors targeting protein-protein interactions that are
      difficult to predict using empirical scoring functions.

PMID- 29456829
TI  - Processing of acceleration and dive data on-board satellite relay tags to
      investigate diving and foraging behaviour in free-ranging marine predators.
AB  - Biologging technologies are changing the way in which the marine environment is
      observed and monitored. However, because device retrieval is typically required
      to access the high-resolution data they collect, their use is generally
      restricted to those animals that predictably return to land. Data abstraction and
      transmission techniques aim to address this, although currently these are limited
      in scope and do not incorporate, for example, acceleration measurements which can
      quantify animal behaviours and movement patterns over fine-scales.In this study,
      we present a new method for the collection, abstraction and transmission of
      accelerometer data from free-ranging marine predators via the Argos satellite
      system. We test run the technique on 20 juvenile southern elephant seals Mirounga
      leonina from the Kerguelen Islands during their first months at sea following
      weaning. Using retrieved archival data from nine individuals that returned to the
      colony, we compare and validate abstracted transmissions against outputs from
      established accelerometer processing procedures.Abstracted transmissions included
      estimates, across five segments of a dive profile, of time spent in prey catch
      attempt (PrCA) behaviours, swimming effort and pitch. These were then summarised
      and compared to archival outputs across three dive phases: descent, bottom and
      ascent. Correlations between the two datasets were variable but generally good
      (dependent on dive phase, marginal R2 values of between .45 and .6 to >.9) and
      consistent between individuals. Transmitted estimates of PrCA behaviours and
      swimming effort were positively biased to those from archival processing.Data
      from this study represent some of the first remotely transmitted quantifications
      from accelerometers. The methods presented and analysed can be used to provide
      novel insight towards the behaviours and movements of free-ranging marine
      predators, such as juvenile southern elephant seals, from whom logger retrieval
      is challenging. Future applications could however benefit from some adaption,
      particularly to reduce positive bias in transmitted PrCA behaviours and swimming
      effort, for which this study provides useful insight.

PMID- 29456830
TI  - Hypoxia-induced the upregulation of stromal cell-derived factor 1 in fibroblast
      like synoviocytes contributes to migration of monocytes into synovium tissue in
      rheumatoid arthritis.
AB  - Background: Rheumatoid arthritis (RA) is an auto-immune disease characterized by
      chronic inflammation of multiple joints. Hypoxia is a constant feature of
      synovial microenvironment in RA. Fibroblast-like synoviocytes (FLSs), which are
      potent effector cells in RA. It has been reported that large numbers of monocytes
      are recruited to the synovium and play an important role in synovial inflammation
      and tissue destruction in RA. However, the mechanism is still unclear. The aim of
      this study is to explore the role of hypoxia microenvironment on the recruitment
      of monocytes and then promote the development of RA. Methods: Rheumatoid
      arthritis model was constructed. Monocytes and FLSs were isolated from rheumatoid
      arthritis mice. RT-PCR, western blot and ELISA were used to detect the expression
      of SDF-1 in FLSs. CXCR4 expression in monocytes was examined by cell
      immunofluorescence and flow cytometry analysis. Transwell assay was performed to
      evaluate the potential of cell migration. Results: We demonstrated that hypoxia
      microenvironment enhanced SDF-1 production of FLSs, which attracted the
      recruitment of CXCR4-expressing monocytes to the synovium and induced monocytes
      differentiation into tissue macrophages. Moreover, these macrophages secreted
      inflammatory factors including IL-6, TNF-alpha, IL-1beta and MMP-3, which
      contributed to the synovial inflammation and tissue destruction in RA.
      Conclusion: The results of this study suggested that hypoxia microenvironment
      played an important role in enhancing SDF-1 production of FLSs. SDF-1/CXCR4 axis
      was involved in the recruitment of monocytes in RA synovium and it might be a
      possible way of inhibiting inflammation and bone erosion in RA.

PMID- 29456831
TI  - Early afterdepolarisation tendency as a simulated pro-arrhythmic risk indicator.
AB  - Drug-induced Torsades de Pointes (TdP) arrhythmia is of major interest in
      predictive toxicology. Drugs which cause TdP block the hERG cardiac potassium
      channel. However, not all drugs that block hERG cause TdP. As such, further
      understanding of the mechanistic route to TdP is needed. Early
      afterdepolarisations (EADs) are a cell-level phenomenon in which the membrane of
      a cardiac cell depolarises a second time before repolarisation, and EADs are seen
      in hearts during TdP. Therefore, we propose a method of predicting TdP using
      induced EADs combined with multiple ion channel block in simulations using
      biophysically-based mathematical models of human ventricular cell
      electrophysiology. EADs were induced in cardiac action potential models using
      interventions based on diseases that are known to cause EADs, including:
      increasing the conduction of the L-type calcium channel, decreasing the
      conduction of the hERG channel, and shifting the inactivation curve of the fast
      sodium channel. The threshold of intervention that was required to cause an EAD
      was used to classify drugs into clinical risk categories. The metric that used L
      type calcium induced EADs was the most accurate of the EAD metrics at classifying
      drugs into the correct risk categories, and increased in accuracy when combined
      with action potential duration measurements. The EAD metrics were all more
      accurate than hERG block alone, but not as predictive as simpler measures such as
      simulated action potential duration. This may be because different routes to EADs
      represent risk well for different patient subgroups, something that is difficult
      to assess at present.

PMID- 29456833
TI  - Work-related acute physical injuries, chronic overuse complaints, and the
      psychosocial work environment in Danish primary care chiropractic practice - a
      cross-sectional study.
AB  - Background: Little is known about the physical and psychosocial work environment
      of chiropractors and their work-related health complaints, and this has never
      been described for Danish chiropractors. The aim of this study was, therefore, to
      describe work-related acute physical injuries, overuse complaints, and
      psychosocial stress in Danish chiropractic work settings. Methods: We developed a
      questionnaire specifically for this study and distributed it electronically in
      August 2016 using SurveyXact to all 575 members of the Danish Chiropractors'
      Association working in primary care clinics. Chiropractors were asked about their
      work-related acute physical injuries and overuse complaints as well as any
      psychosocial stress they experienced at work during the previous year. We
      described our sample and variables using means, medians, ranges, and confidence
      intervals where appropriate. Statistically significant differences between
      genders, types of complaints and injuries, and between clinic owners and
      associates were examined using Chi-square and Fischer's exact tests, where
      appropriate, or by examining confidence intervals for non-overlap. Results: 355
      (65.2%) chiropractors answered the survey. Of these, 216 (61%, 95% CI 56-66) had
      experienced a work-related acute physical injury and/or overuse complaint during
      the previous year. Work-related overuse complaints were most commonly reported in
      the low back, wrist, thumb, and shoulder, and were more common among women (63%,
      95% CI 56-70) than men (51%, 95% CI 43-59). Chiropractors with more than five
      years in practice (59%, 95% CI 52-64) reported significantly fewer work-related
      acute injuries and overuse complaints during the previous year compared with
      chiropractors with less than five years in practice (83%, 95% CI 73-91). In
      general, these practicing Danish chiropractors reported having a good
      psychosocial work environment, and 90% of chiropractors "always" or "often" felt
      that they were motivated and committed to their work. Conclusion: This sample of
      Danish practicing chiropractors commonly reported work-related acute physical
      injuries or overuse complaints. Overuse complaints were most commonly reported in
      the low back, wrist, thumb, and shoulder and were more common among women than
      men. Newly educated chiropractors reported more overuse complaints than
      experienced chiropractors. Collectively, this sample of Danish chiropractors
      reported that they had a good psychosocial work environment.

PMID- 29456832
TI  - Interleukin-25 and eosinophils progenitor cell mobilization in allergic asthma.
AB  - Background: Eosinophil-lineage committed progenitor cells (EoP) migrate from the
      bone marrow and differentiate locally to provide an ongoing source of mature
      eosinophils in asthmatic inflammatory responses in the airways. Sputum levels of
      EoP are increased in asthmatics compared to normal controls suggesting an
      exaggerated eosinophilopoietic environment in the airways. Understanding what
      factors promote EoP traffic to the airways is important to understand the
      diathesis of asthma pathology. Interleukin (IL)-25, is an epithelial-derived
      cytokine that promotes type 2 inflammatory responses. We have previously shown
      that levels of IL-25 and expression of the IL-25 receptor (IL-17RA and IL-17RB)
      on mature eosinophils are greater in allergic asthmatics compared to atopic non
      asthmatics and non-atopic normal controls. In addition, these levels were
      increased significantly increased following allergen inhalation challenge and
      physiologically relevant levels of IL-25 stimulated eosinophil degranulation,
      intracellular IL-5 and IL-13 expression and primed migration to eotaxin. The
      current study, examined the role of IL-25 on allergen-induced trafficking of EoP
      in atopic asthmatics. Methods: Asthmatics (n = 14) who developed allergen-induced
      early and late responses were enrolled in the study. Blood was collected at pre-
      and 24 h post-challenge. At each time point, surface expression of IL-17RA and IL
      17RB on EoP was evaluated by flow cytometry. Migration assays examined the effect
      of IL-25 on EoP chemotactic responses, in vitro. In addition, IL-25 knockout
      ovalbumin (OVA) sensitized and challenged mice were studied to evaluate in vivo
      mobilization effects of IL-25 on newly formed EoP and mature eosinophils.
      Results: There was a significant increase in numbers of blood EoP expressing IL
      17RB, 24 h post-allergen inhalation challenge in allergic asthmatics. Pre
      exposure to IL-25 primed the migrational responsiveness of EoP to stromal cell
      derived factor 1alpha. In OVA-sensitized mice, knocking out IL-25 significantly
      alleviated OVA-induced eosinophil infiltration in the airway and newly formed
      eosinophils were reduced in the lung. Conclusions: The findings of this study
      indicate a potential role for IL-25 in allergen-induced trafficking of EoP to the
      airways and local differentiation promoting tissue eosiniophilia in asthmatic
      responses.

PMID- 29456834
TI  - A retrospective report (2003-2013) of the complications associated with the use
      of a one-man (head and tail) rope recovery system in horses following general
      anaesthesia.
AB  - Background: The mortality rate of horses undergoing general anaesthesia is high
      when compared to humans or small animal patients. One of the most critical
      periods during equine anaesthesia is recovery, as the horse attempts to regain a
      standing position. This study was performed in a private equine practice in
      Belgium that uses a purpose-designed one-man (head and tail) rope recovery system
      to assist the horse during the standing process.The main purpose of the
      retrospective study was to report and analyse complications and the mortality
      rate in horses during recovery from anaesthesia using the described recovery
      system. Information retrieved from the medical records included patient
      signalment, anaesthetic protocol, duration of anaesthesia, ASA grade, type of
      surgery, recovery time and complications during recovery. Sedation was
      administered to all horses prior to recovery with the rope system. Complications
      were divided into major complications in which the horse was euthanized and minor
      complications where the horse survived. Major complications were further
      subdivided into those where the rope system did not contribute to the recovery
      complication (Group 1) and those where it was not possible to determine if the
      rope system was of any benefit (Group 2). Results: Five thousand eight hundred
      fifty two horses recovered from general anaesthesia with rope assistance.
      Complications were identified in 30 (0.51%). Major complications occurred in 12
      horses (0.20%) of which three (0.05%) were assigned to Group 1 and nine (0.15%)
      to Group 2. Three horses in Group 2 suffered musculoskeletal injuries (0.05%).
      Eighteen horses (0.31%) suffered minor complications, of which five (0.08%) were
      categorised as failures of the recovery system. Conclusions: This study reports
      the major and minor complication and mortality rate during recovery from
      anaesthesia using a specific type of rope recovery system. Mortality associated
      with the rope recovery system was low. During recovery from anaesthesia this rope
      system may reduce the risk of lethal complications, particularly major
      orthopaedic injuries.

PMID- 29445447
TI  - Pre-hospital delay in Vietnamese patients hospitalized with a first acute
      myocardial infarction: A short report.
AB  - Background: Administration of coronary reperfusion therapy to patients with an
      acute myocardial infarction (AMI) within the proper timeframe is essential in
      avoiding clinical complications and death. However, the extent of pre-hospital
      delay is unexplored in Vietnam. This report aims to describe the duration of pre
      hospital delay of Hanoi residents hospitalized with a first AMI at the Vietnam
      National Heart Institute .   Methods: A total of 103 Hanoi residents hospitalized
      at the largest tertiary care medical center in the city for first AMI, who have
      information on  prehospital delay was included in this report. Results: One third
      of the study sample was women and mean age was 66 years. The mean and median pre
      hospital delay duration were 14.9 hours and 4.8 hours, respectively. The
      proportion of patients who delayed <6 , 6-<12, and >= 12 hours were 45%, 13%, and
      42%, respectively. Conclusions: Our data shows that a prolonged pre-hospital
      delay is often observed in patients with a first AMI in Vietnam. In order to
      confirm these preliminary descriptive findings, a full-scale investigation of all
      Hanoi residents hospitalized with first AMI is needed. Increasing public
      awareness about AMI treatment is vital in encouraging patients to seek medical
      care timely after experiencing AMI symptoms such that received treatment is most
      effective.

PMID- 29445447
TI  - Pre-hospital delay in Vietnamese patients hospitalized with a first acute
      myocardial infarction: A short report.
AB  - Background: Administration of coronary reperfusion therapy to patients with an
      acute myocardial infarction (AMI) within the proper timeframe is essential in
      avoiding clinical complications and death. However, the extent of pre-hospital
      delay is unexplored in Vietnam. This report aims to describe the duration of pre
      hospital delay of Hanoi residents hospitalized with a first AMI at the Vietnam
      National Heart Institute .   Methods: A total of 103 Hanoi residents hospitalized
      at the largest tertiary care medical center in the city for first AMI, who have
      information on  prehospital delay was included in this report. Results: One third
      of the study sample was women and mean age was 66 years. The mean and median pre
      hospital delay duration were 14.9 hours and 4.8 hours, respectively. The
      proportion of patients who delayed <6 , 6-<12, and >= 12 hours were 45%, 13%, and
      42%, respectively. Conclusions: Our data shows that a prolonged pre-hospital
      delay is often observed in patients with a first AMI in Vietnam. In order to
      confirm these preliminary descriptive findings, a full-scale investigation of all
      Hanoi residents hospitalized with first AMI is needed. Increasing public
      awareness about AMI treatment is vital in encouraging patients to seek medical
      care timely after experiencing AMI symptoms such that received treatment is most
      effective.

PMID- 29456837
TI  - Synaptic neuron-astrocyte communication is supported by an order of magnitude
      analysis of inositol tris-phosphate diffusion at the nanoscale in a model of peri
      synaptic astrocyte projection.
AB  - Background: Astrocytes were conceived for decades only as supporting cells of the
      brain. However, the observation of Ca2+ waves in astrocyte synctitia, their
      neurotransmitter receptor expression and gliotransmitter secretion suggested a
      role in information handling, conception that has some controversies. Synaptic
      Neuron-Astrocyte metabotropic communication mediated by Inositol tris-phosphate
      (SN-AmcIP3) is supported by different reports. However, some models contradict
      this idea and Ca2+ stores are 1000 +/- 325 nm apart from the Postsynaptic Density
      in the Perisynaptic Astrocyte Projections (PAP's), suggesting that SN-AmcIP3 is
      extrasynaptic. However, this assumption does not consider IP3 Diffusion
      Coefficient (Dab), that activates IP3 Receptor (IP3R) releasing Ca2+ from
      intracellular stores. Results: In this work we idealized a model of a PAP (PAPm)
      to perform an order of magnitude analysis of IP3 diffusion using a transient mass
      diffusion model. This model shows that IP3 forms a concentration gradient along
      the PAPm that reaches the steady state in milliseconds, three orders of magnitude
      before IP3 degradation. The model predicts that IP3 concentration near the Ca2+
      stores may activate IP3R, depending upon Phospholipase C (PLC) number and
      activity. Moreover, the PAPm supports that IP3 and extracellular Ca2+ entry
      synergize to promote global Ca2+ transients. Conclusion: The model presented here
      indicates that Ca2+ stores position in PAP's does not limit SN-AmcIP3.

PMID- 29456838
TI  - High throughput imaging cytometer with acoustic focussing.
AB  - We demonstrate an imaging flow cytometer that uses acoustic levitation to
      assemble cells and other particles into a sheet structure. This technique enables
      a high resolution, low noise CMOS camera to capture images of thousands of cells
      with each frame. While ultrasonic focussing has previously been demonstrated for
      1D cytometry systems, extending the technology to a planar, much higher
      throughput format and integrating imaging is non-trivial, and represents a
      significant jump forward in capability, leading to diagnostic possibilities not
      achievable with current systems. A galvo mirror is used to track the images of
      the moving cells permitting exposure times of 10 ms at frame rates of 50 fps with
      motion blur of only a few pixels. At 80 fps, we demonstrate a throughput of 208
      000 beads per second. We investigate the factors affecting motion blur and
      throughput, and demonstrate the system with fluorescent beads, leukaemia cells
      and a chondrocyte cell line. Cells require more time to reach the acoustic focus
      than beads, resulting in lower throughputs; however a longer device would remove
      this constraint.

PMID- 29456839
TI  - Synthesis and Evaluation of a Tetra[6,7]quinoxalinoporphyrazine-based Near
      Infrared Photosensitizer.
AB  - Here we report a near infrared, water-soluble, functional and dendrimeric
      photosensitizer (PS) based on quinoxalinoporphyrazine structure. The
      photophysical properties and in vitro photodynamic therapy results suggest that
      this quinoxalinoporphyrazine-based dendrimer may serve as an efficient near
      infrared (NIR) PS platform.

PMID- 29456840
TI  - Mixed methods evaluation of the impact of a short term training program on
      sterile processing knowledge, practice, and attitude in three hospitals in Benin.
AB  - Background: Proper sterile processing is fundamental to safe surgical practice
      and optimal patient outcomes. Sterile processing practices in low and middle
      income countries often fall short of recommended standards. The impact of
      education and training on sterile processing practices in low and middle-income
      countries is unknown. We designed a sterile processing education course,
      including mentoring, and aimed to evaluate the impact on participants' personal
      knowledge, skills, and practices. We also aimed to identify institutional changes
      in sterile processing practices at participants' work places. Methods: A mixed
      methods design study was conducted using a Hospital Sterile Processing Assessment
      Tool, knowledge tests, and open-ended interviews. Results: Education and
      mentoring improved how workers understood and approached their work and to what
      they paid attention. Sterile processing workers were also better able to identify
      resources available to do their work and showed improved understanding of the
      impact of their work on patient safety. Conclusions: Health care organizations
      seeking to improve surgical outcomes can find easy wins requiring minimal cost
      expenditures by paying attention to sterile processing practices. Investing in
      education and low-cost resources, such as cleaning detergents and brushes, must
      be part of any quality improvement initiative aimed at providing safe surgery in
      low and middle-income countries.

PMID- 29456841
TI  - Successful treatment of extensively drug-resistant Acinetobacter baumannii
      ventriculitis with polymyxin B and tigecycline- a case report.
AB  - Background: Acinetobacter baumannii nosocomial ventriculitis/meningitis,
      especially those due to drug-resistant strains, has substantially increased over
      recent years. However, limited therapeutic options exist for the Acinetobacter
      baumannii ventriculitis/meningitis because of the poor penetration rate of most
      antibiotics through the blood-brain barrier. Case presentation: A 57-year-old
      male patient developed ventriculitis from an extensively drug-resistant strain of
      Acinetobacter baumannii after the decompressive craniectomy for severe traumatic
      brain injury. The patient was successfully treated with intraventricular and
      intravenous polymyxin B together with intravenous tigecycline. Conclusions: The
      case illustrates intraventricular polymyxin B can be a therapeutic option against
      extensively drug-resistant Acinetobacter baumannii ventriculitis.

PMID- 29456843
TI  - Analysis of selected policies towards universal health coverage in Uganda: the
      policy implementation barometer protocol.
AB  - Background: Policy implementation remains an under researched area in most low
      and middle income countries and it is not surprising that several policies are
      implemented without a systematic follow up of why and how they are working or
      failing. This study is part of a larger project called Supporting Policy
      Engagement for Evidence-based Decisions (SPEED) for Universal Health Coverage in
      Uganda. It seeks to support policymakers monitor the implementation of vital
      programmes for the realisation of policy goals for Universal Health Coverage. A
      Policy Implementation Barometer (PIB) is proposed as a mechanism to provide
      feedback to the decision makers about the implementation of a selected set of
      policy programmes at various implementation levels (macro, meso and micro level).
      The main objective is to establish the extent of implementation of malaria,
      family planning and emergency obstetric care policies in Uganda and use these
      results to support stakeholder engagements for corrective action. This is the
      first PIB survey of the three planned surveys and its specific objectives
      include: assessment of the perceived appropriateness of implementation programmes
      to the identified policy problems; determination of enablers and constraints to
      implementation of the policies; comparison of on-line and face-to-face
      administration of the PIB questionnaire among target respondents; and
      documentation of stakeholder responses to PIB findings with regard to corrective
      actions for implementation. Methods/Design: The PIB will be a descriptive and
      analytical study employing mixed methods in which both quantitative and
      qualitative data will be systematically collected and analysed. The first wave
      will focus on 10 districts and primary data will be collected through interviews.
      The study seeks to interview 570 respondents of which 120 will be selected at
      national level with 40 based on each of the three policy domains, 200 from 10
      randomly selected districts, and 250 from 50 facilities. Half of the respondents
      at each level will be randomly assigned to either face-to-face or on-line
      interviews. An integrated questionnaire for these interviews will collect both
      quantitative data through Likert scale-type questions, and qualitative data
      through open-ended questions. And finally focused dialogues will be conducted
      with selected stakeholders for feedback on the PIB findings. Secondary data will
      be collected using data extraction tools for performance statistics. Discussion:
      It is anticipated that the PIB findings and more importantly, the focused
      dialogues with relevant stakeholders, that will be convened to discuss the
      findings and establish corrective actions, will enhance uptake of results and
      effective health policy implementation towards universal health coverage in
      Uganda.

PMID- 29456842
TI  - Hydrogen sulfide, nitric oxide, and neurodegenerative disorders.
AB  - Hydrogen Sulfide (H2S) and Nitric Oxide (NO) have become recognized as important
      gaseous signaling molecules with enormous pharmacological effects, therapeutic
      value, and central physiological roles. NO is one of the most important
      regulators of the pathophysiological condition in central nervous system (CNS).
      It is critical in the various functioning of the brain; however, beyond certain
      concentration/level, it is toxic. H2S was regarded as toxic gas with the smell
      like rotten egg. But, it is now regarded as emerging neuroprotectant and
      neuromodulator. Recently, the use of donors and inhibitors of these signaling
      molecules have helped us to identify their accurate and precise biological
      effects. The most abundant neurotransmitter of CNS (glutamate) is the initiator
      of the reaction that forms NO, and H2S is highly expressed in brain. These
      molecules are shedding light on the pathogenesis of various neurological
      disorders. This review is mainly focused on the importance of H2S and NO for
      normal functioning of CNS.

PMID- 29456844
TI  - An efficient biomarker panel for diagnosis of breast cancer using surface
      enhanced laser desorption ionization time-of-flight mass spectrometry.
AB  - Breast cancer (BC) is the most frequently diagnosed cancer that affects women
      worldwide. Early detection of BC is important to improve survival rates and
      decrease mortality. The aim of the present study was to investigate serum
      biomarkers using surface-enhanced laser desorption ionization time-of-flight mass
      spectrometry (SELDI-TOF-MS) to distinguish patients with BC from the healthy
      population and patients with benign breast diseases (BBDs). A total of 62
      patients with invasive ductal carcinoma, as confirmed by histopathology, and 47
      non-cancerous individuals (NCIs) [16 healthy controls (HCs) and 31 patients with
      BBD] were enrolled in the present study. Serum protein profiles were determined
      by SELDI-TOF-MS using an immobilized metal affinity capture array. Serum from
      patients with BC were compared with that from the HC group using univariate and
      multivariate statistical analyses. A total of 118 clusters were generated from
      the individual serum. Univariate analysis revealed that 5 peaks were
      significantly downregulated (m/z 1,452, 2,670, 3,972, 5,354 and 5,523; P<0.001)
      and 4 were upregulated (m/z 6,850, 7,926, 8,115 and 8,143; P<0.001) in patients
      with BC compared with the HC group. A comparison of patients with BC and patients
      with BBD revealed an additional 9 protein peaks. Among these, 3 peaks (m/z 3,972,
      5,336 and 11,185) were significantly downregulated and 6 peaks (m/z 4,062, 4,071,
      4,609, 6,850, 8,115 and 8,133) were significantly upregulated. A total of 3 peaks
      [mass-to-change ratio (m/z) 3,972, 6,850 and 8,115 (BC2)] were common in both
      sets. The results of the present study suggest that a 4 protein peak set [m/z
      3,972, 6,850 and 8,115 (BC2) and 8,949 (BC3)] could be used to distinguish
      patients with BC from NCI.

PMID- 29456845
TI  - Low carbonyl reductase 1 expression is associated with poor prognosis in patients
      with oral squamous cell carcinoma.
AB  - Carbonyl reductase 1 (CBR1) is an enzyme that catalyzes the reduction of numerous
      compounds by using NADPH-dependent oxidoreductase activity. Decreased expression
      of CBR1 is associated with disease progression and an unfavorable outcome in
      several types of malignancies. The purpose of the current study was to determine
      whether CBR1 expression could be a useful prognostic factor in patients with oral
      squamous cell carcinoma (OSCC). Therefore, its mechanisms of action were
      investigated in order to understand how CBR1 affects cancer cell behavior in
      vitro. CBR1 expression was evaluated using immunohistochemistry and tissue
      samples obtained from 90 patients with OSCC. The associations between CBR1
      expression, clinicopathological characteristics and patient survival were also
      analyzed. In addition, the role of CBR1 in cancer cell invasion and metastasis
      was examined, along with its underlying molecular mechanisms, via transfecting
      CBR1-siRNA into the HSC2 human OSCC cell line. Immunohistochemical analysis
      revealed that biopsy tissue samples of 71.1% of the patients with OSCC were
      positive for CBR1. In addition, CBR1 expression status was correlated with the N
      classification (P<0.0001), stage (P=0.0018) and outcome (P=0.0095). Furthermore,
      a statistical correlation was determined between the protein expression status
      and overall survival (P=0.0171). In vitro studies indicated that the suppression
      of CBR1 by CBR1-siRNA increased cancer cell proliferative, wound healing and
      migratory abilities. These findings suggest that low expression levels of CBR1
      may affect cancer prognosis, and that CBR1 may have potential as a prognostic
      factor for patients with OSCC.

PMID- 29456846
TI  - L-Carnitine supplementation reduces the general fatigue of cancer patients during
      chemotherapy.
AB  - L-Carnitine (LC) plays an important role in the metabolism of fatty acids, and LC
      deficiency is associated with a feeling of weakness or general fatigue. Cancer
      patients receiving chemotherapy often develop LC deficiency, which is considered
      to be a factor contributing to general fatigue. The aim of the present study was
      to evaluate the efficacy of LC supplementation as a treatment for general fatigue
      in cancer patients during chemotherapy. A total of 11 cancer patients who were
      suffering from general fatigue during chemotherapy in our hospital between
      September 2014 and December 2015 were examined (6 cases involved adjuvant
      chemotherapy and 5 cases involved chemotherapy for unresectable or recurrent
      disease). The patients were administered 1,500 mg/day of levocarnitine per os,
      and the change in mean daily fatigue from the baseline to 8 weeks was assessed
      using the Brief Fatigue Inventory. The change in the plasma levels of albumin and
      the lymphocyte counts from the baseline to 8 weeks were also assessed. LC
      supplementation reduced general fatigue in all cases. Moreover, LC
      supplementation maintained the plasma levels of albumin and lymphocyte counts
      during chemotherapy, and enabled patients to continue chemotherapy sequentially
      without dose reduction. Therefore, LC supplementation improved general fatigue in
      all the examined cancer patients during chemotherapy. This treatment may make
      improve the tolerability of chemotherapy in cancer patients by reducing general
      fatigue and improving the nutritional status.

PMID- 29456847
TI  - Curative resection of pancreatic ductal adenocarcinoma developing in the remnant
      pancreas 13 years after distal pancreatectomy for intraductal papillary mucinous
      neoplasms: A case report.
AB  - Intraductal papillary mucinous neoplasms (IPMNs) are characterized by the
      papillary proliferation of atypical mucinous epithelial cells in the pancreatic
      ductal system. There are two recurrence patterns following resection of IPMNs:
      Metachronous multifocal occurrence of IPMNs, and distinct pancreatic ductal
      adenocarcinoma (PDAC) in the remnant pancreas. Several recent studies
      investigated the development of distinct PDAC during follow-up evaluation of
      IPMNs and the incidence rate ranged from 4.5 to 8%. Thus, IMPNs may be a good
      predictor for the early detection of PDAC during observation or after the
      resection of IPMNs. We herein report the rare case of a patient who underwent
      resection of PDAC that developed in the remnant pancreas 13 years after distal
      pancreatectomy with splenectomy for IPMNs. PDAC may develop in the remnant
      pancreas after pancreatectomy for IPMNs; thus, careful long-term follow-up with
      periodic surveillance, at least every 6 months, is warranted.

PMID- 29456849
TI  - High preoperative Glasgow prognostic score is a negative prognostic factor for
      patients with endometrial carcinoma.
AB  - The aim of the present study was to determine the prognostic value of the Glasgow
      prognostic score (GPS) in endometrial carcinoma (EC). Patients with EC who
      underwent surgery at the Shimane University Hospital between January 1997 and
      December 2013 were enrolled (n=118). The associations between pretreatment GPS
      and clinical parameters, including age, histological type, International
      Federation of Gynecology and Obstetrics stage, tumor grade, carbohydrate antigen
      19-9 and carcinoembryonic antigen levels, progression-free survival (PFS), and
      overall survival (OS), were investigated. Survival analysis was performed with
      the Kaplan-Meier method, and prognostic factors were evaluated with Cox's
      proportional hazards regression model. A high pretreatment GPS was associated
      with advanced clinical stage, histological type and tumor grade (P<0.001, P=0.007
      and P=0.006, respectively). Multivariate analysis identified a high GPS as an
      independent negative prognostic factor for PFS and OS (P=0.025 and P=0.044,
      respectively). Therefore, a high pretreatment GPS has prognostic value and the
      potential to be a predictive marker for surgical outcome in patients with EC.
      Evaluation of pretreatment GPS may aid in the identification of high-risk
      populations, which may improve treatment selection and patient outcomes.

PMID- 29456848
TI  - Survival-associated factors of first-line EGFR-tyrosine kinase inhibitor
      responders and non-responders in lung adenocarcinoma patients with common EGFR
      mutations.
AB  - The aim of the present retrospective cohort study was to elucidate the clinical
      presentation of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor
      (TKI) responders and non-responders in lung adenocarcinoma patients with common
      EGFR mutations. The cohort included 131 lung adenocarcinoma patients with common
      exon 19 or exon 21 EGFR mutations, who were receiving first-line EGFR-TKI
      therapy. The patient characteristics, treatment regimen and outcomes were
      recorded and analyzed. Of the 131 patients, 104 (79.3%) responded to treatment,
      while 27 (20.7%) did not. A significantly longer median progression-free survival
      (PFS) [14.3, 95% confidence interval (CI): 12.2-18.4 vs. 5.7, 95% CI: 2.7-9.9
      months; P<0.001] and overall survival (OS) (42.2, 95% CI: 28.1-58.1 vs. 11.5, 95%
      CI: 8.3-19.7 months; P<0.001) were observed in responders compared with non
      responders. In responders, bone [hazard ratio (HR)=1.87, 95% CI: 1.11-3.20,
      P=0.021] and pleural (HR=2.40, 95% CI: 1.37-4.22, P=0.002) metastasis were
      independent factors of PFS. Exon 19 mutations (HR=0.38, 95% CI: 0.19-0.76,
      P=0.006), Eastern Cooperative Oncology Group performance status score >=2
      (HR=3.53, 95% CI: 1.42-8.75, P=0.007) and bone metastasis (HR=2.01, 95% CI: 1.05
      3.85, P=0.034), were independent factors of OS. In non-responders, smoking
      (HR=3.97, 95% CI: 1.13-13.91, P=0.031) was an independent factor of PFS.
      Different survival-associated factors were observed between EGFR-TKI responders
      and non-responders. The development of new treatment strategies should be
      advocated in EGFR-TKI non-responders.

PMID- 29456850
TI  - 18F-fluorodeoxyglucose positron emission tomography/computed tomography for the
      prediction of survival in patients with advanced esophageal cancer who have
      undergone neoadjuvant chemotherapy.
AB  - Neoadjuvant chemotherapy (NAC) is a promising treatment strategy for advanced
      esophageal cancer. However, measures of NAC response assessment and prognostic
      prediction have not yet been established. The aim of this study was to evaluate
      the usefulness of combined 18F-fluorodeoxyglucose positron emission
      tomography/computed tomography (PET/CT). A total of 77 patients with stage IB-IV
      esophageal cancer who were treated with NAC followed by curative resection were
      retrospectively analyzed. PET/CT was performed before and after NAC and 56
      patients were clinical responders. The pretreatment maximal standardized uptake
      value (pre-SUVmax), post-SUVmax and %SUVmax were 11.3+/-5.8, 5.1+/-4.8 and 49.0+/
      35.1%, respectively, for the main tumors (T) and 4.3+/-2.8, 2.5+/-1.9 and 67.0+/
      39.6%, respectively, for the metastatic nodes (N). Among the preoperatively
      available factors, clinical response (P=0.018), post-SUVmax-N (P=0.0001) and
      %SUVmax-T (P=0.0031) were significant prognostic factors by univariate analysis.
      The multivariate analysis identified post-SUVmax-N as the only significant
      prognostic predictor (P=0.0254). Patients with a post-SUVmax-N of <3.0 exhibited
      significantly fewer pathological metastatic nodes and better disease-free
      survival compared with patients with a post-SUVmax-N >3.0. Therefore, post-SUVmax
      N may be a useful prognostic predictor in patients with advanced esophageal
      cancer who are treated with NAC followed by surgery.

PMID- 29456851
TI  - Duodenal mucinous adenocarcinoma presenting as ileus, obstructive jaundice and
      massive ascites: A case report.
AB  - Duodenal mucinous adenocarcinoma (DMA) is a malignancy with a rather low
      morbidity. However, its incidence in China has not been clearly determined. We
      herein report a case of a 70-year-old female patient who presented with ileus,
      obstructive jaundice and massive ascites simultaneously. Gastroendoscopy revealed
      copious amounts of colloidal mucin in the gastric cavity. The neoplasm was not
      visualized on computed tomography or magnetic resonance imaging, and an
      exploratory laparotomy was performed to investigate the abdomen. During the
      operation, the anterior wall of the gastric antrum was incised to explore the
      first and second portions of the duodenum, as well as the gastric lumen, and a
      neoplasm sized ~2.0 cm was identified at the antimesenteric border of the
      duodenal bulb after clearing the colloidal mucin content of the stomach and
      duodenum. Gastrojejunostomy rather than radical resection was performed due to
      the poor condition of the patient. The postoperative histopathological
      examination of the colloidal substance removed from the duodenal cavity revealed
      mucinous adenocarcinoma. On immunohistochemical analysis, the tissue stained
      positive for pan-cytokeratin, cytokeratin 19, CDX-2, carcinoembryonic antigen and
      Ki-67 (8%), and negative for excision repair-1. The general condition of the
      patient postoperatively was poor; thus, adjuvant chemotherapy was not
      administered and the patient finally succumbed to the disease 42 days after
      surgery.

PMID- 29456852
TI  - Xanthogranulomatous pituitary adenoma: A case report and literature review.
AB  - Xanthogranuloma, also referred to as cholesterol granuloma or xanthogranulomatous
      reaction, is a granulomatous lesion that is infrequently found in the sellar and
      parasellar regions. Xanthogranulomatous pituitary adenoma is relatively rare and,
      thus, the etiology, diagnosis, management and prognosis of this condition remain
      incompletely understood. We herein report the case of a 56-year-old female
      patient who presented to our institution with intermittent headache, vomiting and
      distending pain in the bilateral orbital regions. Brain magnetic resonance
      imaging revealed a sellar mass with a heterogeneous signal. The mass was
      subtotally resected, and histopathological examination confirmed the diagnosis of
      xanthogranulomatous pituitary adenoma. Although the patient's symptoms were
      relieved following surgical treatment, intractable hyponatremia and diabetes
      insipidus developed and she received hormone replacement therapy. At the last
      follow-up (November 2016), the patient remained recurrence-free. A total of 14
      cases of pituitary adenoma with concomitant xanthogranuloma were identified in
      the literature, and the clinical and radiological manifestations are discussed.
      Sellar xanthogranuloma is usually associated with craniopharyngioma or Rathke's
      cleft cyst; however, it may also occur in isolation. Xanthogranulomatous
      pituitary adenomas are infrequent, making their diagnosis challenging. Surgical
      resection is the preferred treatment, and attention should be paid to
      postoperative hypopituitarism and development of diabetes insipidus.

PMID- 29456853
TI  - Crizotinib-associated toxic epidermal necrolysis in an ALK-positive advanced
      NSCLC patient.
AB  - Crizotinib is an oral small-molecule inhibitor of anaplastic lymphoma kinase
      (ALK) tyrosine-kinase that has been approved for treating patients with advanced
      echinoderm microtubule associated protein like 4-ALK rearranged non-small-cell
      lung cancer (NSCLC). Toxic epidermal necrolysis (TEN) is a rare adverse event
      associated with crizotinib. The present study reported a case of a 75-year-old
      Chinese male patient with advanced NSCLC with ALK fusion, who developed TEN after
      56 days of crizotinib treatment and demised due to this dermatological adverse
      event. The occurrence of severe cutaneous necrolysis that predominantly involves
      the skin and mucous membranes during crizotinib treatment should alert clinicians
      to be aware of TEN and take prompt actions.

PMID- 29456854
TI  - Novel BRAF mutation in melanoma: A case report.
AB  - In melanoma, a number of specific genetic and genomic aberrations have been
      identified to be important in tumorigenesis. In particular, the mutant B-Raf
      proto-oncogene, Serine/Threonine kinase (BRAF) gene is the target of tailored
      therapy with kinase inhibitor molecules. Identification of the array of mutations
      in patients with melanoma will be useful in determining a genetic profile of the
      tumor with potential implications for treatment decisions. A rare aminoacidic
      insertion in codon 599 of the BRAF gene (c.1797_1798insACA, T599insT) was
      detected by using both direct (Sanger) sequencing and pyrosequencing techniques
      in a metastatic melanoma of a female elderly patient. As suggested in other
      clinical contexts including pilocytic astrocytoma, papillary thyroid carcinomas
      and anaplastic thyroid carcinomas, this unusual mutation may be associated with a
      modified spatial structure of activated P-loop, resulting in a constitutional
      activation of the BRAF protein. The patient died shortly following the test, thus
      no biological therapy was performed. Comparable data regarding treatment of
      melanoma patients with rare BRAF mutations is lacking, and the response to BRAF
      inhibitors requires further investigation.

PMID- 29456855
TI  - Metformin and aspirin treatment could lead to an improved survival rate for Type
      2 diabetic patients with stage II and III colorectal adenocarcinoma relative to
      non-diabetic patients.
AB  - Metformin, the drug of choice in the treatment of type 2 diabetes mellitus (DM2),
      in addition to aspirin (ASA), the drug prescribed for cardioprotection of
      diabetic and non-diabetic patients, have an inhibitory effect on cancer cell
      survival. The present population-based study conducted in the province of Trieste
      (Italy), aimed to investigate the prevalence of DM2 in patients with colorectal
      adenocarcinoma (CRC) and survival for CRC in diabetic and nondiabetic patients.
      All permanent residents diagnosed with a CRC between 2004 and 2007 were
      ascertained through the regional health information system. CRC-specific and
      relative survival probabilities were computed for each group of patients defined
      by CRC stage, presence or absence of DM2 treated with metformin, and presence or
      absence of daily ASA therapy. A total of 515 CRC patients without DM2 and 156
      with DM2 treated with metformin were enrolled in the study. At the time of CRC
      diagnosis, 71 (14%) nondiabetic and 39 (25%) diabetic patients were taking ASA
      daily. The five-year relative survival for stage III CRC was 101% [95% confidence
      interval (CI)=76-126] in the 18 patients with DM2 treated with metformin and ASA,
      55% (95% CI=31-78) in the 23 without DM2 treated with ASA, 55% (95% CI=45-65) in
      the 150 without DM2 not taking ASA, and 29% (95% CI=13-45) in the 43 with DM2
      treated with metformin, however not with ASA. The findings support the hypothesis
      of a possible inhibitory effect of metformin and ASA on CRC cells. Randomized
      controlled trials are required to verify this hypothesis.

PMID- 29456856
TI  - Design principles of perovskites for solar-driven thermochemical splitting of
      CO2.
AB  - Perovskites are attractive redox materials for thermo/electrochemical fuel
      synthesis. To design perovskites with balanced redox energetics for
      thermochemically splitting CO2, the activity of lattice oxygen vacancies and
      stability against crystal phase changes and detrimental carbonate formation are
      predicted for a representative range of perovskites by electronic structure
      computations. Systematic trends in these materials properties when doping with
      selected metal cations are described in the free energy range defined for
      isothermal and temperature-swing redox cycles. To confirm that the predicted
      materials properties root in the bulk chemical composition, selected perovskites
      are synthesized and characterized by X-ray diffraction, transmission electron
      microscopy, and thermogravimetric analysis. On one hand, due to the oxidation
      equilibrium, none of the investigated compositions outperforms non-stoichiometric
      ceria - the benchmark redox material for CO2 splitting with temperature-swings in
      the range of 800-1500  degrees C. On the other hand, certain promising
      perovskites remain redox-active at relatively low oxide reduction temperatures at
      which ceria is redox-inactive. This trade-off in the redox energetics is
      established for YFeO3, YCo0.5Fe0.5O3 and LaFe0.5Ni0.5O3, identified as stable
      against phase changes and capable to convert CO2 to CO at 600  degrees C and 10
      mbar CO in CO2, and to being decomposed at 1400  degrees C and 0.1 mbar O2 with
      an enthalpy change of 440-630 kJ mol-1 O2.

PMID- 29456857
TI  - Platinum-free, graphene based anodes and air cathodes for single chamber
      microbial fuel cells.
AB  - Microbial fuel cells (MFCs) exploit the ability of microorganisms to generate
      electrical power during metabolism of substrates. However, the low efficiency of
      extracellular electron transfer from cells to the anode and the use of expensive
      rare metals as catalysts, such as platinum, limit their application and
      scalability. In this study we investigate the use of pristine graphene based
      electrodes at both the anode and the cathode of a MFC for efficient electrical
      energy production from the metabolically versatile bacterium Rhodopseudomonas
      palustris CGA009. We achieve a volumetric peak power output (PV) of up to 3.51 +/
      0.50 W m-3 using graphene based aerogel anodes with a surface area of 8.2 m2 g
      1. We demonstrate that enhanced MFC output arises from the interplay of the
      improved surface area, enhanced conductivity, and catalytic surface groups of the
      graphene based electrode. In addition, we show a 500-fold increase in PV to 1.3
      +/- 0.23 W m-3 when using a graphene coated stainless steel (SS) air cathode,
      compared to an uncoated SS cathode, demonstrating the feasibility of a platinum
      free, graphene catalysed MFCs. Finally, we show a direct application for
      microwatt-consuming electronics by connecting several of these coin sized devices
      in series to power a digital clock.

PMID- 29456858
TI  - Enhanced biostability and cellular uptake of zinc oxide nanocrystals shielded
      with a phospholipid bilayer.
AB  - The widespread use of ZnO nanomaterials for biomedical applications, including
      therapeutic drug delivery or stimuli-responsive activation, as well as imaging,
      imposes a careful control over the colloidal stability and long-term behaviour of
      ZnO in biological media. Moreover, the effect of ZnO nanostructures on living
      cells, in particular cancer cells, is still under debate. This paper discusses
      the role of surface chemistry and charge of zinc oxide nanocrystals, of around 15
      nm in size, which influence their behaviour in biological fluids and effect on
      cancer cells. In particular, we address this problem by modifying the surface of
      pristine ZnO nanocrystals (NCs), rich of hydroxyl groups, with positively charged
      amino-propyl chains or, more innovatively, by self-assembling a double-lipidic
      membrane, shielding the ZnO NCs. Our findings show that the prolonged immersion
      in simulated human plasma and in the cell culture medium leads to highly
      colloidally dispersed ZnO NCs only when coated by the lipidic bilayer. In
      contrast, the pristine and amine-functionalized NCs form huge aggregates after
      already one hour of immersion. Partial dissolution of these two samples into
      potentially cytotoxic Zn2+ cations takes place, together with the precipitation
      of phosphate and carbonate salts on the NCs' surface. When exposed to living HeLa
      cancer cells, higher amounts of lipid-shielded ZnO NCs are internalized with
      respect to the other samples, thus showing a reduced cytotoxicity, based on the
      same amount of internalized NCs. These results pave the way for the development
      of novel theranostic platforms based on ZnO NCs. The new formulation of ZnO
      shielded with a lipid-bilayer will prevent strong aggregation and premature
      degradation into toxic by-products, and promote a highly efficient cell uptake
      for further therapeutic or diagnostic functions.

PMID- 29456859
TI  - Acute myeloid leukemia in a father and son with a germline mutation of ASXL1.
AB  - Background: Myelodysplastic syndromes and acute myeloid leukemia usually occur
      sporadically in older adults. More recently cases of familial acute myeloid
      leukemia and/or myelodysplastic syndrome have been reported. Case presentation:
      Currently we report a father and son who both developed myelodysplastic syndrome
      that progressed to acute myeloid leukemia. Both patients were found to have the
      identical mutation of ASXL1 on nextgen sequencing of both hematologic and
      nonhematologic tissues. Conclusions: These cases support the diagnosis of a
      germline mutation of ASXL1.

PMID- 29456860
TI  - Protein kinase inhibitors for acute leukemia.
AB  - Conventional treatments for acute leukemia include chemotherapy, radiation
      therapy, and intensive combined treatments (including bone marrow transplant or
      stem cell transplants). Novel treatment approaches are in active development.
      Recently, protein kinase inhibitors are on clinical trials and offer hope as new
      drugs for acute leukemia treatment. This review will provide a brief summary of
      the protein kinase inhibitors in clinical applications for acute leukemia
      treatment.

PMID- 29456861
TI  - Critical airway compression caused by a large mediastinal tumour with spontaneous
      haemorrhage.
AB  - We report the case of a 77-year-old woman presenting with out-of-hospital cardiac
      arrest, which was then interpreted as an acute, life-threatening critical airway
      compression by a huge mediastinal tumour without appropriate diagnosis. Emergency
      extracorporeal membrane oxygenation was cannulated for sufficient respiratory
      support after spontaneous circulation was regained. After the multidisciplinary
      team, involving thoracic surgeons, discussed the resectability of the mediastinal
      tumour, the patient underwent successful resection of the mediastinal tumour
      through a median sternotomy. The pathological report demonstrated an
      intrathoracic goitre with spontaneous haemorrhage and haematoma formation, and
      the patient was discharged with favourable respiratory and neurological outcomes.

PMID- 29456862
TI  - Thin laryngeal foreign bodies in infants: diagnostic potential of MDCT.
AB  - A laryngeal foreign body (FB) is a significant, life-threatening event in the
      paediatric population. Incomplete airways obstruction by a thin, laminar,
      radiolucent FB lodged in the glottis or supraglottis is a rare occurrence that
      may present with non-specific symptoms, absence of chest findings, and normal
      radiographic investigations, resulting in misdiagnosis, delay in diagnosis, or
      prolonged recovery. We report two cases of 10-month-old male infants, each with a
      thin radiolucent FB lodged between the vocal folds that was detected with low
      dose multidetector computed tomography (MDCT) and thin-slice reconstruction. Both
      infants presented with symptoms of respiratory airway inflammation at clinical
      examination and negative neck and chest radiographs. FBs were removed by direct
      laryngoscopy, without complications. In our experience, low-dose MDCT with thin
      slice reconstruction is particularly useful for diagnosis in cases of suspected
      FB aspiration with uncertain clinical presentation and negative radiographic
      exams.

PMID- 29456863
TI  - Lung parenchymal involvement of primary bone marrow follicular lymphoma: a rare
      case study.
AB  - A 76-year-old man presented with shortness of breath. Computed tomography
      revealed ground-glass opacity and interlobular thickening in the right lower
      lobe. Blood examination showed elevated levels of white blood cell count and
      lymphocytes. Bone marrow aspiration revealed low-grade follicular lymphoma.
      Histopathological examination of the surgical lung biopsy from the right lower
      lobe demonstrated usual interstitial pneumonia and scattered aggregation of
      lymphocytes with poorly formed non-necrotizing granuloma. An 18F
      fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET
      CT) did not show intense uptake in areas other than the right lower lobe. We
      concluded that the granuloma in the lung was presumed to be a sarcoid reaction
      associated with bone marrow follicular lymphoma, and the intense 18F-FDG uptake
      in the right lower lobe might have been due to a sarcoid reaction.
      Immunohistochemistry or other genetic examinations are important even if 18F-FDG
      uptake on PET-CT seems to be a false-positive because of the possibility of a
      sarcoid reaction.

PMID- 29456865
TI  - A real world example of coverage with evidence development in Australia -
      ipilimumab for the treatment of metastatic melanoma.
AB  - Background: Australian Government subsidisation of ipilimumab for the treatment
      of patients with metastatic melanoma was conditional on the sponsor entering a
      'managed entry scheme' to assess the 2-year overall survival rate in metastatic
      melanoma patients who received ipilimumab in the first year of Pharmaceutical
      Benefits Scheme listing. Methods: All unresectable stage IIIc / IV metastatic
      melanoma patients treated with at least one dose of ipilimumab therapy in
      Australia from the PBS listing date to a time point 12 months later (i.e. from 1
      Aug-2013 to 31-Jul-2014) were invited to participate. Overall survival at 2 years
      post treatment initiation was measured, with Cox regression analysis used to
      examine the relationship between survival and patient baseline characteristics.
      Results: The evaluable population (910 patients) was on average 63.3 years old,
      male (70.1%) and treated in a public hospital (64.4%) in an urban area (76.5%).
      The majority of patients were treatment naive (63.3%), did not have brain
      metastases (71.1%), and were classified as ECOG performance status 0 or 1
      (90.4%). The 2 year overall survival rate was conservatively calculated to be at
      least 23.9% and potentially as high as 34.2%. A significant difference in overall
      survival at 2 years was demonstrated across the categories of ECOG performance
      status (p < 0.0001), M-status (p = 0.0005) and treatment status (p = 0.0114). No
      statistical difference in survival rate was observed when examining brain
      metastases vs no brain metastases (p = 0.2622), treatment at private vs public
      hospitals (p = 0.7601) nor treatment in the urban vs rural setting (p = 0.5048).
      Conclusions: The 2 year overall survival rate for all patients receiving PBS
      subsidised ipilimumab in Australia from the first year Pharmaceutical Benefits
      Scheme cohort is estimated to be between 23.9% and 34.2%, which is higher than
      the 23.5% observed in the key ipilimumab registrational trial. Results and
      learnings from the ipilimumab 'managed entry scheme' illustrate that early access
      with the promise of future evidence to confirm a medicine's cost-effectiveness
      can work, but needs to be carefully considered, constructed and managed.

PMID- 29456866
TI  - Guidelines for recognition of occupational cancers in Korea: the results of
      scientific review by Korean Society of Occupational and Environmental Medicine
      (2013-2016).
AB  - This thematic collection includes the articles to review eleven occupational
      cancer related risks or working conditions and to propose the guidelines of S.
      Korea.

PMID- 29456864
TI  - Curative GnRHa treatment has an unexpected repressive effect on Sertoli cell
      specific genes.
AB  - Background: Follicle stimulating hormone and testosterone stimulate Sertoli cells
      to support germ cell function and differentiation. During mini-puberty, when
      gonadotropin (GnRH) stimulates increases in plasma luteinizing hormone (LH) and
      testosterone levels, gonocytes are transformed into Ad spermatogonia. In
      cryptorchidism, impaired gonadotropin secretion during mini-puberty results in
      insufficient LH and testosterone secretion, impaired gonocyte transition to Ad
      spermatogonia, and perturbed Sertoli cell proliferation. Treatment with a
      gonadotropin-releasing hormone agonist (GnRHa/Buserelin) induced gonocytes to
      differentiate into Ad spermatogonia and rescued fertility. The present study
      evaluated the impact of low LH secretion on Sertoli cell function by comparing
      differential gene expression data between testes with low LH that lacked Ad
      spermatogonia (Ad-) and testes that completed mini-puberty (Ad+). Furthermore, we
      analyzed changes in the transcription of selected Sertoli cell specific genes in
      response to GnRHa treatment. Results: Ad- testes showed reduced expression of
      nine out of 40 selected Sertoli cell specific genes compared to Ad+ testes. GnRHa
      treatment repressed most of the Sertoli cell specific genes, including the
      inhibins, but it increased the expression of genes that regulate apoptosis
      (FASLG) and proliferation (GDNF). Conclusions: Impaired-minipuberty with
      decreased LH and testosterone levels affected Ad and Sertoli cell development
      through positive and negative regulation of morphoregulatory and apoptotic genes.
      GnRHa treatment had a repressive effect on most Sertoli cell specific genes,
      which suggested that Sertoli cells underwent a cellular rearrangement. We propose
      that gonadotropin-dependent increases in FASLG and GDNF expression drove Sertoli
      cell proliferation and germ cell self-renewal and supported the transition of
      gonocytes to Ad spermatogonia, independent of inhibins.

PMID- 29456867
TI  - Heterologous and endogenous U6 snRNA promoters enable CRISPR/Cas9 mediated genome
      editing in Aspergillus niger.
AB  - Background: U6 promoters have been used for single guide RNA (sgRNA)
      transcription in the clustered regularly interspaced short palindromic
      repeats/CRISPR-associated protein (CRISPR/Cas9) genome editing system. However,
      no available U6 promoters have been identified in Aspergillus niger, which is an
      important industrial platform for organic acid and protein production. Two
      CRISPR/Cas9 systems established in A. niger have recourse to the RNA polymerase
      II promoter or in vitro transcription for sgRNA synthesis, but these approaches
      generally increase cloning efforts and genetic manipulation. The validation of
      functional RNA polymerase II promoters is therefore an urgent need for A. niger.
      Results: Here, we developed a novel CRISPR/Cas9 system in A. niger for sgRNA
      expression, based on one endogenous U6 promoter and two heterologous U6
      promoters. The three tested U6 promoters enabled sgRNA transcription and the
      disruption of the polyketide synthase albA gene in A. niger. Furthermore, this
      system enabled highly efficient gene insertion at the targeted genome loci in A.
      niger using donor DNAs with homologous arms as short as 40-bp. Conclusions: This
      study demonstrated that both heterologous and endogenous U6 promoters were
      functional for sgRNA expression in A. niger. Based on this result, a novel and
      simple CRISPR/Cas9 toolbox was established in A. niger, that will benefit future
      gene functional analysis and genome editing.

PMID- 29456869
TI  - Cognitive fluctuations in Parkinson's disease dementia: blood pressure lability
      as an underlying mechanism.
AB  - Background: Cognitive fluctuations refer to alterations in cognition, attention,
      or arousal occurring over minutes to hours, most commonly in patients with
      dementias associated with advanced Lewy body pathology. Their pathophysiologic
      underpinning remains undetermined. Case presentation: We documented serial blood
      pressure (BP) measurements in an 86-year-old man with Parkinson's disease
      dementia experiencing cognitive fluctuations during an office visit. This
      patient's associated dysautonomia included labile BP with orthostatic hypotension
      and nocturnal hypertension. A spontaneous episode of unresponsiveness occurred
      while his BP was 72/48. His mental status began to recover immediately as his BP
      increased to 84/56 when he was placed in a recumbent position; it fully returned
      to baseline when it reached 124/66 within 1 min. His heart rate remained in the
      mid-to-high 60s throughout. Subsequent treatment with midodrine markedly reduced
      the frequency of cognitive fluctuations. Conclusions: Paroxysmal hypotension may
      represent an explanatory mechanism for cognitive fluctuations, a common clinical
      feature in patients with Parkinson's disease dementia and dementia with Lewy
      bodies.

PMID- 29456868
TI  - Cinnamomum zeylanicum bark essential oil induces cell wall remodelling and
      spindle defects in Candida albicans.
AB  - Background: Cinnamon (Cinnamomum zeylanicum) bark extract exhibits potent
      inhibitory activity against Candida albicans but the antifungal mechanisms of
      this essential oil remain largely unexplored. Results: We analyzed the impact of
      cinnamon bark oil on C. albicans RSY150, and clinical strains isolated from
      patients with candidemia and candidiasis. The viability of RSY150 was
      significantly compromised in a dose dependent manner when exposed to cinnamon
      bark oil, with extensive cell surface remodelling at sub inhibitory levels (62.5
      MUg/mL). Atomic force microscopy revealed cell surface exfoliation, altered
      ultrastructure and reduced cell wall integrity for both RSY150 and clinical
      isolates exposed to cinnamon bark oil. Cell wall damage induced by cinnamon bark
      oil was confirmed by exposure to stressors and the sensitivity of cell wall
      mutants involved in cell wall organization, biogenesis, and morphogenesis. The
      essential oil triggered cell cycle arrest by disrupting beta tubulin
      distribution, which led to mitotic spindle defects, ultimately compromising the
      cell membrane and allowing leakage of cellular components. The multiple targets
      of cinnamon bark oil can be attributed to its components, including
      cinnamaldehyde (74%), and minor components (< 6%) such as linalool (3.9%),
      cinamyl acetate (3.8%), alpha-caryophyllene (5.3%) and limonene (2%). Complete
      inhibition of the mitotic spindle assembly was observed in C. albicans treated
      with cinnamaldehyde at MIC (112 MUg/mL). Conclusions: Since cinnamaldehyde
      disrupts both the cell wall and tubulin polymerization, it may serve as an
      effective antifungal, either by chemical modification to improve its specificity
      and efficacy or in combination with other antifungal drugs.

PMID- 29456870
TI  - A psychosocial intervention for the management of functional dysphonia: complex
      intervention development and pilot randomised trial.
AB  - Background: Medically unexplained loss or alteration of voice-functional
      dysphonia-is the commonest presentation to speech and language therapists (SLTs).
      Besides the impact on personal and work life, functional dysphonia is also
      associated with increased levels of anxiety and depression and poor general
      health. Voice therapy delivered by SLTs improves voice but not these associated
      symptoms. The aims of this research were the systematic development of a complex
      intervention to improve the treatment of functional dysphonia, and the trialling
      of this intervention for feasibility and acceptability to SLTs and patients in a
      randomised pilot study. Methods: A theoretical model of medically unexplained
      symptoms (MUS) was elaborated through literature review and synthesis. This was
      initially applied as an assessment format in a series of patient interviews. Data
      from this stage and a small consecutive cohort study were used to design and
      refine a brief cognitive behavioural therapy (CBT) training intervention for a
      SLT. This was then implemented in an external pilot patient randomised trial
      where one SLT delivered standard voice therapy or voice therapy plus CBT to 74
      patients. The primary outcomes were of the acceptability of the intervention to
      patients and the SLT, and the feasibility of changing the SLT's clinical practice
      through a brief training. This was measured through monitoring treatment flow and
      through structured analysis of the content of intervention for treatment fidelity
      and inter-treatment contamination. Results: As measured by treatment flow, the
      intervention was as acceptable as standard voice therapy to patients. Analysis of
      treatment content showed that the SLT was able to conduct a complex CBT
      formulation and deliver novel treatment strategies for fatigue, sleep, anxiety
      and depression in the majority of patients. On pre-post measures of voice and
      quality of life, patients in both treatment arms improved. Conclusion: These
      interventions were acceptable to patients. Emotional and psychosocial issues
      presented routinely in the study patient group and CBT techniques were used,
      deliberately and inadvertently, in both treatment arms. This CBT "contamination"
      of the voice therapy only arm reflects the chief limitation of the study: one
      therapist delivered both treatments. Trial registration: Registered with the
      ISRCTN under the title: Training a Speech and Language Therapist in Cognitive
      Behavioural Therapy to treat Functional Dysphonia - A Randomised Controlled
      Trial.Trial Identifier: ISRCTN20582523 Registered 19/05/2010; retrospectively
      registered. http://www.isrctn.com/ISRCTN20582523.

PMID- 29456872
TI  - Accuracy in local staging of prostate cancer by adding a three-dimensional T2
      weighted sequence with radial reconstructions in magnetic resonance imaging.
AB  - Background: The evidence supporting the use of magnetic resonance imaging (MRI)
      in prostate cancer detection has been established, but its accuracy in local
      staging is questioned. Purpose: To investigate the additional value of multi
      planar radial reconstructions of a three-dimensional (3D) T2-weighted (T2W) MRI
      sequence, intercepting the prostate capsule perpendicularly, for improving local
      staging of prostate cancer. Material and Methods: Preoperative, bi-parametric
      prostate MRI examinations in 94 patients operated between June 2014 and January
      2015 where retrospectively reviewed by two experienced abdominal radiologists.
      Each patient was presented in two separate sets including diffusion-weighted
      imaging, without and with the 3D T2W set that included radial reconstructions.
      Each set was read at least two months apart. Extraprostatic tumor extension (EPE)
      was assessed according to a 5-point grading scale. Sensitivity and specificity
      for EPE was calculated and presented as receiver operating characteristics (ROC)
      with area under the curve (AUC), using histology from whole-mount prostate
      specimen as gold standard. Inter-rater agreement was calculated for the two
      different reading modes using Cohen's kappa. Results: The AUC for detection of
      EPE for Readers 1 and 2 in the two-dimensional (2D) set was 0.70 and 0.68,
      respectively, and for the 2D + 3D set 0.62 and 0.65, respectively. Inter-rater
      agreement (Reader 1 vs. Reader 2) on EPE using Cohen's kappa for the 2D and 2D +
      3D set, respectively, was 0.42 and 0.17 (i.e. moderate and poor agreement,
      respectively). Conclusion: The addition of 3D T2W MRI with radial reconstructions
      did not improve local staging in prostate cancer.

PMID- 29456871
TI  - GestationaL Obesity Weight management: Implementation of National Guidelines
      (GLOWING): a pilot cluster randomised controlled trial of a guideline
      implementation intervention for the management of maternal obesity by midwives.
AB  - Background: Weight management in pregnancy guidelines exist, although
      dissemination alone is an ineffective means of implementation. Midwives identify
      the need for support to overcome complex barriers to practice. An evaluation of
      an intervention to support midwives' guideline implementation would require a
      large-scale cluster randomised controlled trial. A pilot study is necessary to
      explore the feasibility of delivery and evaluation prior to a definitive trial.
      The GestationaL Obesity Weight management: Implementation of National Guidelines
      (GLOWING) trial aims to test whether it is feasible and acceptable to deliver a
      behaviour change intervention to support midwives' implementation of weight
      management guidelines. Methods: GLOWING is a multi-centre parallel group pilot
      cluster randomised controlled trial comparing the delivery of a behaviour change
      intervention for midwives versus usual practice. Four NHS Trusts (clusters) will
      be randomised to intervention and control arms, stratified by size of maternity
      services. The intervention uses social cognitive theory and consists of face-to
      face midwifery training plus information resources for routine practice. The main
      outcomes are whether the intervention and trial procedures are feasible and
      acceptable to participants and the feasibility of recruitment and data collection
      for a definitive trial. Target recruitment involves all eligible midwives in the
      intervention arm recruited to receive the intervention, 30 midwives and pregnant
      women per arm for baseline and outcome questionnaire data collection and 20
      midwives and women to provide qualitative data. All quantitative and qualitative
      analyses will be descriptive with the purpose of informing the development of the
      definitive trial. Discussion: This pilot study has been developed to support
      community midwives' implementation of guidelines. Community midwives have been
      selected as they usually carry out the booking appointment which includes
      measuring and discussing maternal body mass index. A cluster design is the gold
      standard in implementation research as there would be a high risk of
      contamination if randomisation was at individual midwife level: community
      midwives usually work in locality-based teams, interact on a daily basis, and
      share care of pregnant women. The results of the pilot trial will be used to
      further develop and refine GLOWING prior to a definitive trial to evaluate
      effectiveness and cost-effectiveness. Trial registration: ISRCTN46869894;
      retrospectively registered 25th May 2016.

PMID- 29456873
TI  - The Rockefeller University Clinical Scholars (KL2) Program 2006-2016.
AB  - Introduction and Methods: The Rockefeller Clinical Scholars (KL2) Program began
      in 1976 and transitioned into a 3-year Master's degree program in 2006 when
      Rockefeller joined the NIH Clinical and Translational Science Award (CTSA)
      program. The program consists of ~15 trainees supported by the CTSA KL2 award and
      University funds. It is designed to provide an optimal environment for junior
      translational investigators to develop team science and leadership skills by
      designing and performing a human subjects protocol under the supervision of a
      distinguished senior investigator mentor and a team of content expert educators.
      This is complemented by a tutorial focused on important translational skills.
      Results: Since 2006, 40 Clinical Scholars have graduated from the programs and
      gone on to careers in academia (72%), government service (5%), industry (15%),
      and private medical practice (3%); two (5%) remain in training programs. 39/40
      remain in translational research careers with 23 NIH awards totaling $23 million,
      foundation and philanthropic support of $20.3 million, and foreign government and
      foundation support of $6 million. They have made wide ranging scientific
      discoveries and have endeavored to translate those discoveries into improved
      human health. Conclusion: The Rockefeller Clinical Scholars (KL2) program
      provides one model for translational science training.

PMID- 29456874
TI  - A Novel Approach to Data Collection for Difficult Structures: Data Management for
      Large Numbers of Crystals with the BLEND Software.
AB  - The present article describes how to use the computer program BLEND to help
      assemble complete datasets for the solution of macromolecular structures,
      starting from partial or complete datasets, derived from data collection from
      multiple crystals. The program is demonstrated on more than two hundred X-ray
      diffraction datasets obtained from 50 crystals of a complex formed between the
      SRF transcription factor, its cognate DNA, and a peptide from the SRF cofactor
      MRTF-A. This structure is currently in the process of being fully solved. While
      full details of the structure are not yet available, the repeated application of
      BLEND on data from this structure, as they have become available, has made it
      possible to produce electron density maps clear enough to visualise the potential
      location of MRTF sequences.

PMID- 29456875
TI  - Delayed Presentation of Submucosal Retained Toothbrush from Self-Inflicted Injury
      in Patient with Schizophrenia.
AB  - Foreign body ingestion occurs in not only children but also adults, particularly
      those with history of neurologic disease, alcohol use, or psychiatric disease. We
      present the case of a 40-year-old male with schizophrenia who presented to the
      emergency room with a long history of pharyngeal foreign body sensation which had
      recently progressed to include trismus, odynophagia, and dyspnea. Flexible
      laryngoscopy demonstrated fullness of the right posterior pharyngeal wall and
      computed tomography (CT) showed a linear opaque foreign body extending from the
      level of the oropharynx to the thyroid ala. Further history elicited that he
      stabbed himself in the pharynx two years prior with a toothbrush following a
      command hallucination. The toothbrush was removed uneventfully via an external
      approach. The patient was discharged with psychiatry follow-up. This case is
      unusual due to the submucosal location of the foreign body and the length of
      retention. It demonstrates the atypical nature which patients with comorbid
      psychiatric illness may present following foreign body injury and the use of an
      external surgical approach for the removal of a retained foreign body based on CT
      reconstruction.

PMID- 29456876
TI  - Cobalt-Catalyzed Stereoretentive Hydrogen Isotope Exchange of C(sp3)-H Bonds.
AB  - Cobalt dialkyl complexes bearing alpha-diimine ligands proved to be active
      precatalysts for the nondirected, C(sp3)-H selective hydrogen isotope exchange
      (HIE) of alkylarenes using D2 gas as the deuterium source. Alkylarenes with a
      variety of substitution patterns and heteroatom substituents on the arene ring
      were successfully labeled, enabling high levels of incorporation into primary,
      secondary, and tertiary benzylic C(sp3)-H bonds. In some cases, the HIE proceeded
      with high diastereoselectivity and application of the cobalt-catalyzed method to
      enantioenriched substrates with benzylic stereocenters provided enantioretentive
      hydrogen isotope exchange at tertiary carbons.

PMID- 29456877
TI  - A dextran-based probe for the targeted magnetic resonance imaging of tumours
      expressing prostate-specific membrane antigen.
AB  - Safe imaging agents able to render the expression and distribution of cancer
      receptors, enzymes or other biomarkers would facilitate clinical screening of the
      disease. Here, we show that diamagnetic dextran particles coordinated to a urea
      based targeting ligand for prostate-specific membrane antigen (PSMA) enable
      targeted magnetic resonance imaging (MRI) of the PSMA receptor. In a xenograft
      model of prostate cancer, micromolar concentrations of the dextran -ligand probe
      provided sufficient signal to specifically detect PSMA-expressing tumours via
      chemical exchange saturation transfer MRI. The dextran-based probe could be
      detected via the contrast originating from dextran hydroxyl protons, thereby
      avoiding the need of chemical substitution for radioactive or metallic labelling.
      Because dextrans are currently used clinically, dextran-based contrast agents may
      help extend receptor-targeted imaging to clinical MRI.

PMID- 29456878
TI  - Non-destructive two-photon excited fluorescence imaging identifies early nodules
      in calcific aortic-valve disease.
AB  - Calcifications occur during the development of healthy bone, and at the onset of
      calcific aortic-valve disease (CAVD) and many other pathologies. Although the
      mechanisms regulating early calcium deposition are not fully understood, they may
      provide targets for new treatments and for early interventions. Here, we show
      that two-photon excited fluorescence (TPEF) can provide quantitative and
      sensitive readouts of calcific nodule formation, in particular in the context of
      CAVD. Specifically, by means of the decomposition of TPEF spectral images from
      excised human CAVD valves and from rat bone prior to and following
      demineralization, as well as from calcific nodules formed within engineered gels,
      we identified an endogenous fluorophore that correlates with the level of
      mineralization in the samples. We then developed a ratiometric imaging approach
      that provides a quantitative readout of the presence of mineral deposits in early
      calcifications. TPEF should enable non-destructive, high-resolution imaging of
      three-dimensional tissue specimens for the assessment of the presence of
      calcification.

PMID- 29456880
TI  - Cost-effectiveness of nivolumab in patients with advanced renal cell carcinoma
      treated in the United States.
AB  - Background: We evaluated the cost-effectiveness of nivolumab versus everolimus in
      patients with advanced renal cell carcinoma (RCC) from a US payer perspective.
      Methods: A partitioned survival model consisting of three health states,
      progression-free survival (PFS), progressive disease, and death, was developed to
      evaluate the cost-effectiveness of intravenous nivolumab versus oral everolimus
      over a lifetime. The proportion of patients in each state was calculated based on
      parametric distributions fitted to PFS and overall survival (OS) data from
      CheckMate 025 (N = 821), a large randomized phase 3 trial of nivolumab versus
      everolimus for advanced RCC. Health state utility data were derived from
      CheckMate 025 EQ-5D data. Scenario analyses and deterministic and probabilistic
      sensitivity analyses assessed the impact of uncertainty in model inputs on
      outcomes. Results: Over a 25-year lifetime horizon, treatment with nivolumab
      resulted in a gain of 0.64 quality-adjusted life-years (QALYs) versus everolimus.
      Nivolumab had greater total costs versus everolimus ($US197,089 vs. $US163,902),
      mainly due to higher acquisition costs. The incremental cost-utility ratio
      (ICUR), a measure of incremental costs divided by incremental QALYs, was
      $US51,714 per QALY gained for nivolumab versus everolimus, and an incremental
      cost-effectiveness ratio was $US44,576 per life-year gained for nivolumab versus
      everolimus. In sensitivity analyses, average body weight had the greatest impact
      on the ICUR for nivolumab versus everolimus (base case $US51,714; range $US8863
      $US94,566). At a $US150,000 willingness-to-pay (WTP) threshold, nivolumab had a
      91.7% probability of being cost-effective versus everolimus. Conclusions: In the
      United States, at a WTP threshold of $US150,000 per QALY, nivolumab was found to
      be cost-effective. Key drivers of cost-effectiveness were survival inputs for OS
      and the average weight of patients; the latter directly affects nivolumab drug
      acquisition cost.

PMID- 29456879
TI  - Subcortical Effects on Voice and Fluency in Dysarthria: Observations from
      Subthalamic Nucleus Stimulation.
AB  - Objective: Parkinson's disease (PD), caused by basal ganglia dysfunction, is
      associated with motor disturbances including dysarthria. Stimulation of the
      subthalamic nucleus, a preferred treatment targeting basal ganglia function,
      improves features of the motor disorder, but has uncertain effects on speech.We
      studied speech during contrasting stimulation states to reveal subcortical
      effects on voice and articulation. Measures were made on selected samples of
      spontaneous and repeated speech. Methods: Persons with Parkinson's disease (PWP)
      who had undergone bilateral deep brain stimulation of the subthalamic nucleus
      (DBS-STN) provided spontaneous speech samples and then repeated portions of their
      monologue both on and off stimulation. Excerpts were presented in a listening
      protocol probing intelligibility. Also analysed were a continuous phrase
      repetition task and a second spontaneous speech sample. Fundamental frequency
      (F0), harmonic-to-noise ratio (HNR), jitter, shimmer and fluency were measured in
      these three speech samples performed with DBS stimulation on and off. Results:
      During subcortical stimulation, spontaneous excerpts were less intelligible than
      repeated excerpts. F0 and HNR were higher and shimmer was decreased in repetition
      and stimulation. Articulatory dysfluencies were increased for spontaneous speech
      and during stimulation in all three speech samples. Conclusion: Deep brain
      stimulation disrupts fluency and improves voice in spontaneous speech, reflecting
      an inverse influence of subcortical systems on articulatory posturing and
      laryngeal mechanisms. Better voice and less dysfluency in repetition may occur
      because an external model reduces the speech planning burden, as seen for gait
      and arm reach. These orthogonal results for fluency versus phonatory competence
      may account for ambivalent reports from dysarthric speakers and reveal the
      complexity of subcortical control of motor speech.

PMID- 29456882
TI  - Effects of osmolytes and macromolecular crowders on stable GAAA tetraloops and
      their preference for a CG closing base pair.
AB  - Osmolytes and macromolecular crowders have the potential to influence the
      stability of secondary structure motifs and alter preferences for conserved
      nucleic acid sequences in vivo. To further understand the cellular function of
      RNA we observed the effects of a model osmolyte, polyethylene glycol (PEG) 200,
      and a model macromolecular crowding agent, PEG 8000, on the GAAA tetraloop motif.
      GAAA tetraloops are conserved, stable tetraloops, and are critical participants
      in RNA tertiary structure. They also have a thermodynamic preference for a CG
      closing base pair. The thermal denaturation of model hairpins containing GAAA
      loops was monitored using UV-Vis spectroscopy in the presence and absence of PEG
      200 or PEG 8000. Both of the cosolutes tested influenced the thermodynamic
      preference for a CG base pair by destabilizing the loop with a CG closing base
      pair relative to the loop with a GC closing base pair. This result also extended
      to a related DNA triloop, which provides further evidence that the interactions
      between the loop and closing base pair are identical for the d(GCA) triloop and
      the GAAA tetraloop. Our results suggest that in the presence of model PEG
      molecules, loops with a GC closing base pair may retain some preferential
      interactions with the cosolutes that are lost in the presence of the CG closing
      base pair. These results reveal that relatively small structural changes could
      influence how neutral cosolutes tune the stability and function of secondary
      structure motifs in vivo.

PMID- 29456883
TI  - Estimating common dolphin bycatch in the pole-and-line tuna fishery in the
      Azores.
AB  - Small-scale artisanal fisheries can have a significant negative impact in
      cetacean populations. Cetacean bycatch has been documented in the pole-and-line
      tuna fishery in the Azores with common dolphins being the species more frequently
      taken. Based on data collected by observers on ~50% of vessels operating from
      1998 to 2012, we investigate the influence of various environmental and fisheries
      related factors in common dolphin bycatch and calculate fleet-wide estimates of
      total bycatch using design-based and model-based methods. Over the 15-year study
      dolphin bycatch occurred in less than 0.4% of the observed fishing events.
      Generalized additive modelling results suggest a significant relationship between
      common dolphin bycatch and duration of fishing events, sea surface temperature
      and location. Total bycatch calculated from the traditional stratified ratio
      estimation approach was 196 (95% CI: 186-205), while the negative binomial GAM
      estimated 262 (95% CI: 249-274) dolphins. Bycatch estimates of common dolphin
      were similar using statistical approaches suggesting that either of these methods
      may be used in future bycatch assessments for this fishery. Our work shows that
      rates of common dolphin bycatch in the pole-and-line tuna fishery in the Azores
      are low, despite considerable variations between years. Dolphins caught were
      released alive although the fate of these individuals is unknown. Continued
      monitoring will provide a better understanding of dolphin bycatch and more
      accurate estimates essential in the development of potential mitigation measures.

PMID- 29456881
TI  - Multimodality Treatment of Advanced Non-small Cell Lung Cancer: Where are we with
      the Evidence?
AB  - Purpose of review: The majority of patients with non-small cell lung cancer
      (NSCLC) present with advanced disease and overall survival rates are poor. This
      article outlines the current and outstanding evidence for the use of
      multimodality treatment in this group of patients, including in combination with
      an increasing number of treatment options, such as immunotherapy and genotype
      targeted small molecule inhibitors. Recent findings: Optimal therapy for
      surgically resectable stage III disease remains debatable and currently the
      choice of treatment reflects each individual patient's disease characteristics
      and the expertise and opinion of the thoracic multi-disciplinary team. Evidence
      for a distinct oligometastatic state in which improved outcomes can be achieved
      remains minimal and there is as yet no consensus definition for oligometastatic
      lung cancer. Whilst there is supporting evidence for the aggressive management of
      isolated metastases, the use of consolidative therapy for multiple metastases
      remains unproven. Summary: Evolution of new RT technologies, improved surgical
      technique and a plethora of interventional-radiology-guided ablative therapies
      are widening the choice of available treatment modalities to patients with NSCLC.
      In the setting of resectable locally advanced disease and the oligometastatic
      state, there is a growing need for randomised comparison of the available
      treatment modalities to guide both treatment and patient selection.

PMID- 29456884
TI  - Desiccation resistance: effect of cuticular hydrocarbons and water content in
      Drosophila melanogaster adults.
AB  - Background: The insect cuticle covers the whole body and all appendages and has
      bi-directionnal selective permeability: it protects against environmental stress
      and pathogen infection and also helps to reduce water loss. The adult cuticle is
      often associated with a superficial layer of fatty acid-derived molecules such as
      waxes and long chain hydrocarbons that prevent rapid dehydration. The
      waterproofing properties of cuticular hydrocarbons (CHs) depend on their chain
      length and desaturation number. Drosophila CH biosynthesis involves an enzymatic
      pathway including several elongase and desaturase enzymes. Methods: The link
      between desiccation resistance and CH profile remains unclear, so we tested (1)
      experimentally selected desiccation-resistant lines, (2) transgenic flies with
      altered desaturase expression and (3) natural and laboratory-induced CH variants.
      We also explored the possible relationship between desiccation resistance,
      relative water content and fecundity in females. Results: We found that increased
      desiccation resistance is linked with the increased proportion of desaturated
      CHs, but not with their total amount. Experimentally-induced desiccation
      resistance and CH variation both remained stable after many generations without
      selection. Conversely, flies with a higher water content and a lower proportion
      of desaturated CHs showed reduced desiccation resistance. This was also the case
      in flies with defective desaturase expression in the fat body. Discussion: We
      conclude that rapidly acquired desiccation resistance, depending on both CH
      profile and water content, can remain stable without selection in a humid
      environment. These three phenotypes, which might be expected to show a simple
      relationship, turn out to have complex physiological and genetic links.

PMID- 29456885
TI  - Genus-level phylogeny of cephalopods using molecular markers: current status and
      problematic areas.
AB  - Comprising more than 800 extant species, the class Cephalopoda (octopuses, squid,
      cuttlefish, and nautiluses) is a fascinating group of marine conchiferan
      mollusks. Recently, the first cephalopod genome (of Octopus bimaculoides) was
      published, providing a genomic framework, which will enable more detailed
      investigations of cephalopod characteristics, including developmental,
      morphological, and behavioural traits. Meanwhile, a robust phylogeny of the
      members of the subclass Coleoidea (octopuses, squid, cuttlefishes) is crucial for
      comparative and evolutionary studies aiming to investigate the group's traits and
      innovations, but such a phylogeny has proven very challenging to obtain. Here, we
      present the results of phylogenetic inference at the genus level using
      mitochondrial and nuclear marker sequences available from public databases.
      Topologies are presented which show support for (1) the monophyly of the two main
      superorders, Octobrachia and Decabrachia, and (2) some of the interrelationships
      at the family level. We have mapped morphological characters onto the tree and
      conducted molecular dating analyses, obtaining congruent results with previous
      estimates of divergence in major lineages. Our study also identifies unresolved
      phylogenetic relationships within the cephalopod phylogeny and insufficient
      taxonomic sampling among squids excluding the Loliginidae in the Decabrachia and
      within the Order Cirromorphida in the Octobrachia. Genomic and transcriptomic
      resources should enable resolution of these issues in the relatively near future.
      We provide our alignment as an open access resource, to allow other researchers
      to reconstruct phylogenetic trees upon this work in the future.

PMID- 29456886
TI  - Heterogenic transplantation of bone marrow-derived rhesus macaque mesenchymal
      stem cells ameliorates liver fibrosis induced by carbon tetrachloride in mouse.
AB  - Liver fibrosis is a disease that causes high morbidity and has become a major
      health problem. Liver fibrosis can lead to the end stage of liver diseases
      (livercirrhosisand hepatocellularcarcinoma). Currently, liver transplantation is
      the only effective treatment for end-stage liver disease. However, the shortage
      of organ donors, high cost of medical surgery, immunological rejection and
      transplantation complications severely hamper liver transplantation therapy.
      Mesenchymal stem cells (MSCs) have been regarded as promising cells for clinical
      applications in stem cell therapy in the treatment of liver diseases due to their
      unique multipotent differentiation capacity, immunoregulation and paracrine
      effects. Although liver fibrosis improvements by MSC transplantation in
      preclinical experiments as well as clinical trials have been reported, the in
      vivo fate of MSCs after transportation and their therapeutic mechanisms remain
      unclear. In this present study, we isolated MSCs from the bone marrow of rhesus
      macaques. The cells exhibited typical MSC markers and could differentiate into
      chondrocytes, osteocytes, and adipocytes, which were not affected by labeling
      with enhanced green fluorescent protein (EGFP). The harvested MSCs respond to
      interferon-gamma stimulation and have the ability to inhibit lymphocyte
      proliferation in vitro. EGFP-labeled MSCs (1 * 106 cells) were transplanted into
      mice with carbon tetrachloride-induced liver fibrosis via tail vein injection.
      The ability of the heterogenic MSC infusion to ameliorate liver fibrosis in mice
      was evaluated by a blood plasma chemistry index, pathological examination and
      liver fibrosis-associated gene expression. Additionally, a small number of MSCs
      that homed and engrafted in the mouse liver tissues were evaluated by
      immunofluorescence analysis. Our results showed that the transplantation of
      heterogenic MSCs derived from monkey bone marrow can be used to treat liver
      fibrosis in the mouse model and that the paracrine effects of MSCs may play an
      important role in the improvement of liver fibrosis.

PMID- 29456887
TI  - A new slider turtle (Testudines: Emydidae: Deirochelyinae: Trachemys) from the
      late Hemphillian (late Miocene/early Pliocene) of eastern Tennessee and the
      evolution of the deirochelyines.
AB  - Trachemys (Testudines: Emydidae) represents one of the most well-known turtle
      genera today. The evolution of Trachemys, while being heavily documented with
      fossil representatives, is not well understood. Numerous fossils from the late
      Hemphillian Gray Fossil Site (GFS) in northeastern Tennessee help to elucidate
      its evolution. The fossil Trachemys at the GFS represent a new species. The new
      taxon, Trachemys haugrudi, is described, and currently represents the most
      thoroughly described fossil emydid species known. A phylogenetic analysis,
      including 31 species, focusing on the subfamily Deirochelyinae is performed that
      includes the new fossil species, along with numerous other modern and fossil
      deirochelyine species, representing the first phylogenetic analysis published
      that includes several fossil deirochelyines. The phylogenetic analysis, utilizing
      morphological evidence, provides monophyletic clades of all modern
      deirochelyines, including Chrysemys, Deirochelys, Pseudemys, Malaclemys,
      Graptemys, and Trachemys. A strict consensus tree finds the recently described
      fossil species Graptemys kerneri to be part of a clade of Graptemys + Malaclemys.
      Three fossil taxa, including one previously referred to Pseudemys (Pseudemys
      caelata) and two to Deirochelys (Deirochelys carri and Deirochelys floridana) are
      found to form a clade with modern Deirochelys reticularia reticularia, with D.
      floridana sister to the other members of the clade. Chrysemys is found to be part
      of a basal polytomy with Deirochelys in relation to other deirochelyine taxa. Two
      fossil taxa previously referred to Chrysemys (Chrysemys timida and Chrysemys
      williamsi) form a paraphyly with the modern Chrysemys picta picta and
      Deirochelys, and may be referable to distinct genera. Additionally, fossil taxa
      previously attributed to Trachemys (Trachemys hillii, Trachemys idahoensis,
      Trachemys inflata, and Trachemys platymarginata) and T. haugrudi are found to
      form a clade separate from clades of northern and southern Trachemys species,
      potentially suggesting a distinct lineage of Trachemys with no modern survivors.
      Hypotheses of phylogenetic relationships mostly agree between the present study
      and previous ones, although the inclusion of fossil taxa provides further clues
      to the evolution of parts of the Deirochelyinae. The inclusion of more fossil
      taxa and characters may help resolve the placement of some taxa, and further
      elucidate the evolution of these New World turtles.

PMID- 29456888
TI  - An observational study on risk of secondary cancers in chronic myeloid leukemia
      patients in the TKI era in the United States.
AB  - Introduction: The treatment with tyrosine kinase inhibitors (TKIs) has
      drastically improved the outcome of chronic myeloid leukemia (CML) patients. This
      study was conducted to examine the risk of secondary cancers (SCs) in the CML
      patients who were diagnosed and treated in the TKI era in the United States.
      Methods: The surveillance epidemiology and end results (SEER) database was used
      to identify CML patients who were diagnosed and received treatment during January
      2002-December 2014. Standardized incidence ratios (SIRs) and absolute excess
      risks (AER) were calculated. Results: Overall, 511 SCs (excluding acute leukemia)
      developed in 9,200 CML patients followed for 38,433 person-years. The risk of
      developing SCs in the CML patients was 30% higher than the age, sex and race
      matched standard population (SIR 1.30, 95% CI: 1.2-1.40; p < 0.001). The SIRs for
      CLL (SIR 3.4, 95% CI: 2-5.5; p < 0.001), thyroid (SIR 2.2, 95% CI: 1.2-3.5; p <
      0.001), small intestine (SIR 3.1, 95% CI: 1.1-7; p = 0.004), gingiva (SIR 3.7,
      95% CI: 1.2-8.7; p = 0.002), stomach (SIR 2.1, 95% CI: 1.1-3.5; p = 0.005), lung
      (SIR 1.4, 95% CI: 1.1-1.7; p = 0.006) and prostate (SIR 1.3, 95% CI: 1.02-1.6; p
      = 0.026) cancer among CML patients were significantly higher than the general
      population. The risk of SCs was higher irrespective of age and it was highest in
      the period 2-12 months after the diagnosis of CML. The risk of SCs in women was
      similar to that of the general population. Conclusion: CML patients diagnosed and
      treated in the TKI era in the United States are at an increased risk of
      developing a second malignancy. The increased risk of SCs in the early period
      after CML diagnosis suggests that the risk of SCs may be increased due to the
      factors other than TKIs treatment.

PMID- 29456890
TI  - A six-year grazing exclusion changed plant species diversity of a Stipa
      breviflora desert steppe community, northern China.
AB  - Excluding grazers is one of most efficient ways to restore degraded grasslands in
      desert-steppe communities, but may negatively affect the recovery of plant
      species diversity. However, diversity differences between grazed and fenced
      grasslands in desert-steppe are poorly known. In a Stipa breviflora desert steppe
      community in Northern China, we established six plots to examine spatial patterns
      of plant species diversity under grazed and fenced conditions, respectively. We
      addressed three aspects of species diversity: (1) The logistic, exponential and
      power models were used to describe the species-area curve (SAR). Species
      richness, abundance and Shannon diversity values change differently with
      increasing sampling areas inside and outside of the fence. The best fitted model
      for SAR was the logistic model. Excluding grazers had a significant impact on the
      shape of SAR. (2) Variograms was applied to examine the spatial characteristics
      of plant species diversity. We found strong spatial autocorrelations in the
      diversity variables both inside and outside the fence. After grazing exclusion,
      the spatial heterogeneity decreased in species richness, increased in abundance
      and did not change in Shannon diversity. (3) We used variance partitioning to
      determine the relative contributions of spatial and environmental factors to
      plant species diversity patterns. Environmental factors explained the largest
      proportion of variation in species diversity, while spatial factors contributed
      little. Our results suggest that grazing enclosures decreased species diversity
      patterns and the spatial pattern of the S. breviflora desert steppe community was
      predictable.

PMID- 29456889
TI  - A bibliometric analysis in gene research of myocardial infarction from 2001 to
      2015.
AB  - Objectives: We aimed to evaluate the global scientific output of gene research of
      myocardial infarction and explore their hotspots and frontiers from 2001 to 2015,
      using bibliometric methods. Methods: Articles about the gene research of
      myocardial infarction between 2001 and 2015 were retrieved from the Web of
      Science Core Collection (WoSCC). We used the bibliometric method and Citespace V
      to analyze publication years, journals, countries, institutions, research areas,
      authors, research hotspots, and trends. We plotted the reference co-citation
      network, and we used key words to analyze the research hotspots and trends.
      Results: We identified 1,853 publications on gene research of myocardial research
      from 2001 to 2015, and the annual publication number increased with time.
      Circulation published the highest number of articles. United States ranked
      highest in the countries with most publications, and the leading institute was
      Harvard University. Relevant publications were mainly in the field of
      Cardiovascular system cardiology. Keywords and references analysis indicated that
      gene expression, microRNA and young women were the research hotspots, whereas
      stem cell, chemokine, inflammation and cardiac repair were the frontiers.
      Conclusions: We depicted gene research of myocardial infarction overall by
      bibliometric analysis. Mesenchymal stem cells Therapy, MSCs-derived microRNA and
      genetic modified MSCs are the latest research frontiers. Related studies may
      pioneer the future direction of this filed in next few years. Further studies are
      needed.

PMID- 29456891
TI  - Frequency and developmental timing of linear enamel hypoplasia defects in Early
      Archaic Texan hunter-gatherers.
AB  - Digital photographs taken under controlled conditions were used to examine the
      incidence of linear enamel hypoplasia defects (LEHs) in burials from the Buckeye
      Knoll archaeological site (41VT98 Victoria county, Texas), which spans the Early
      to Late Archaic Period (ca. 2,500-6,500 BP uncorrected radiocarbon). The majority
      (68 of 74 burials) date to the Texas Early Archaic, including one extremely early
      burial dated to 8,500 BP. The photogrammetric data collection method also results
      in an archive for Buckeye Knoll, a significant rare Archaic period collection
      that has been repatriated and reinterred. We analyzed the incidence and
      developmental timing of LEHs in permanent canines. Fifty-nine percent of
      permanent canines (n = 54) had at least one defect. There were no significant
      differences in LEH frequency between the maxillary and mandibular canines (U =
      640.5, n1 = 37, n2 = 43, p = .110). The sample studied (n = 92 permanent canines)
      had an overall mean of 0.93 LEH defect per tooth, with a median of one defect,
      and a mode of zero defects. Average age at first insult was 3.92 (median = 4.00,
      range = 2.5-5.4) and the mean age of all insults per individual was 4.18 years
      old (range = 2.5-5.67). Age at first insult is consistent with onset of weaning
      stress-the weaning age range for hunter-gatherer societies is 1-4.5. Having an
      earlier age of first insult was associated with having more LEHs (n = 54, rho = 
      0.381, p = 0.005).

PMID- 29456892
TI  - Under the armor: X-ray computed tomographic reconstruction of the internal
      skeleton of Coahomasuchus chathamensis (Archosauria: Aetosauria) from the Upper
      Triassic of North Carolina, USA, and a phylogenetic analysis of Aetosauria.
AB  - Aetosauria is a clade of heavily armored, quadrupedal omnivorous to herbivorous
      archosaurs known from the Late Triassic across what was the supercontinent of
      Pangea. Their abundance in many deposits relative to the paucity of other
      Triassic herbivores indicates that they were key components of Late Triassic
      ecosystems. However, their evolutionary relationships remain contentious due, in
      large part, to their extensive dermal armor, which often obstructs observation of
      internal skeletal anatomy and limits access to potentially informative
      characters. In an attempt to address this problem we reanalyzed the holotype of a
      recently described species of Coahomasuchus, C. chathamensis, from the Sanford
      sub-basin of North Carolina using computed tomography (CT). CT scans of the
      holotype specimen clarify preservation of the skeleton, revealing several
      articulated vertebrae and ribs, an isolated vertebra, left ulna, left scapula,
      and the right humerus, though none of the material resulted in updated
      phylogenetic scorings. Reexamination of aetosaur materials from the holotype
      locality also indicates that several isolated osteoderms and elements of the
      appendicular skeleton are newly referable. Based on these results, we update the
      Coahomasuchus chathamensis hypodigm and conduct a revised phylogenetic analysis
      with improved character scorings for Coahomasuchus and several other aetosaurs.
      Our study recovers Coahomasuchus in a polytomy with Aetosaurus and the
      Typothoracinae, in contrast with a recent analysis that recovered Coahomasuchus
      as a wild-card taxon.

PMID- 29456893
TI  - The effect of supragingival glycine air polishing on periodontitis during
      maintenance therapy: a randomized controlled trial.
AB  - Background: Glycine air polishing has been proved to be safe, comfortable and
      time-saving. Whether it could substitute ultrasonic scaling to remove dental
      plaque biofilm during periodontal maintenance remains unclear. The purposes of
      this study were to evaluate the effect of supragingival glycine air polishing
      (SGAP) on the subgingival periodontal pathogens during maintenance therapy and to
      check the association of periodontal pathogens and clinical parameters. Methods:
      Twenty-three chronic periodontitis patients during their maintenance therapy were
      enrolled in the 12-week study. According to randomized split-mouth design, the
      test side was treated with SGAP (65 MUm), while the control side was treated with
      supragingival ultrasonic scaling and polishing (SUSP) with rubber cup. Clinical
      examination including plaque index (PLI), probing depth (PD), bleeding index (BI)
      were performed at baseline and 12 weeks post-treatment. Sampling of the
      subgingival plaque at each investigational site (mesiobuccal site of the
      mandibular first molar) was performed at baseline and 2, 4, 8, 12 weeks after
      maintenance treatment. Four periodontal pathogens including Porphyromonas
      gingivalis, Tannerella forsythia, Treponema denticola and Fusobacterium nucleatum
      were detected by 16S rDNA polymerase chain reaction. Results: Clinical status
      generally improved after treatment in both groups. PLI in both groups, PD in SGAP
      group and bleeding on probing (%) in SUSP group significantly decreased after
      treatment (p < 0.05). There was no significant difference of clinical parameters
      between two groups before and after treatment. The detection rates of P.
      gingivalis, T. denticola in both groups, T. forsythia in SUSP group and F.
      nucleatum in SGAP group decreased after maintenance treatment in both groups,
      although no significant difference was found, and it rebound to baseline level at
      12 weeks after maintenance treatment. There was no significant difference between
      SGAP group and SUSP group at any time point. T. denticola-positive sites had
      significantly greater BI than T. denticola-negative sites (p < 0.05). Discussion:
      Supragingival glycine air polishing had a reliable effect in removing subgingival
      dental plaque biofilm during maintenance period, and three months may be a proper
      maintenance interval for pockets not more than 5 mm.

PMID- 29456894
TI  - The state of OA: a large-scale analysis of the prevalence and impact of Open
      Access articles.
AB  - Despite growing interest in Open Access (OA) to scholarly literature, there is an
      unmet need for large-scale, up-to-date, and reproducible studies assessing the
      prevalence and characteristics of OA. We address this need using oaDOI, an open
      online service that determines OA status for 67 million articles. We use three
      samples, each of 100,000 articles, to investigate OA in three populations: (1)
      all journal articles assigned a Crossref DOI, (2) recent journal articles indexed
      in Web of Science, and (3) articles viewed by users of Unpaywall, an open-source
      browser extension that lets users find OA articles using oaDOI. We estimate that
      at least 28% of the scholarly literature is OA (19M in total) and that this
      proportion is growing, driven particularly by growth in Gold and Hybrid. The most
      recent year analyzed (2015) also has the highest percentage of OA (45%). Because
      of this growth, and the fact that readers disproportionately access newer
      articles, we find that Unpaywall users encounter OA quite frequently: 47% of
      articles they view are OA. Notably, the most common mechanism for OA is not Gold,
      Green, or Hybrid OA, but rather an under-discussed category we dub Bronze:
      articles made free-to-read on the publisher website, without an explicit Open
      license. We also examine the citation impact of OA articles, corroborating the so
      called open-access citation advantage: accounting for age and discipline, OA
      articles receive 18% more citations than average, an effect driven primarily by
      Green and Hybrid OA. We encourage further research using the free oaDOI service,
      as a way to inform OA policy and practice.

PMID- 29456895
TI  - Calibration adjustments to address bias in mortality analyses due to informative
      sampling-a census-linked survey analysis in Switzerland.
AB  - Background: Sampling bias, like survey participants' nonresponse, needs to be
      adequately addressed in the analysis of sampling designs. Often survey weights
      will be calibrated on specific covariates related to the probability of selection
      and nonresponse to get representative population estimates. However, such
      calibrated survey (CS) weights are usually constructed for cross-sectional
      results, but not for longitudinal analyses. For example, when the outcome of
      interest is time to death, and sampling selection is related to time to death and
      censoring, sampling is informative. Then, unweighted or CS weighted inferential
      statistical analyses may be biased. In 2010, Switzerland changed from a decennial
      full enumeration census to a yearly registry-based (i.e., data from harmonised
      community registries) and a survey-based census system. In the present study, we
      investigated the potential bias due to informative sampling when time to death is
      the outcome of interest, using data from the new Swiss census system. Methods: We
      analysed more than 6.5 million individuals aged 15 years or older from registry
      based census data from years 2010 to 2013, linked with mortality records up to
      end of 2014. Out of this population, a target sample of 3.5% was sampled from the
      Swiss Federal Statistical Office (SFSO) in a stratified yearly micro census. The
      SFSO calculated CS weights to enable representative population estimates from the
      micro census. We additionally constructed inverse probability (IP) weights, where
      we used survival information in addition to known sampling covariates. We
      compared CS and IP weighted mortality rates (MR) and life expectancy (LE) with
      estimates from the underlying population. Additionally, we performed a simulation
      study under different sampling and nonresponse scenarios. Results: We found that
      individuals who died in 2011, had a 0.67 (95% CI [0.64-0.70]) times lower odds of
      participating in the 2010 micro census, using a multivariable logistic regression
      model with covariates age, gender, nationality, civil status, region and survival
      information. IP weighted MR were comparable to estimates from the total
      population, whereas CS weighted MR underestimated the population MR in general.
      The IP weighted LE estimates at age 30 years for men were 50.9 years (95% CI
      [50.2-51.6] years), whereas the CS weighted overestimated LE by 2.5 years. Our
      results from the simulation study confirmed that IP weighted models are
      comparable to population estimates. Conclusion: Mortality analyses based on the
      new Swiss survey-based census system may be biased, because of informative
      sampling. We conclude that mortality analyses based on census-linked survey data
      have to be carefully conducted, and if possible, validated by registry
      information to allow for unbiased interpretation and generalisation.

PMID- 29456897
TI  - Detection of Essential Tremor at the [Formula: see text]-Band.
AB  - Essential tremor (ET) is a neurological disorder characterized by rhythmic,
      involuntary shaking of a part or parts of the body. The most common tremor is
      seen in the hands/arms and fingers. This paper presents an evaluation of ETs
      monitoring based on finger-to-nose test measurement as captured by small wireless
      devices working in shortwave or [Formula: see text]-band frequency range. The
      acquired signals in terms of amplitude and phase information are used to detect a
      tremor in the hands. Linearly transforming raw phase data acquired in the
      [Formula: see text]-band were carried out for calibrating the phase information
      and to improve accuracy. The data samples are used for classification using
      support vector machine algorithm. This model is used to differentiate the tremor
      and nontremor data efficiently based on secondary features that characterize ET.
      The accuracy of our measurements maintains linearity, and more than 90% accuracy
      rate is achieved between the feature set and data samples.

PMID- 29456896
TI  - Factors associated with elevated blood pressure or hypertension in Afro-Caribbean
      youth: a cross-sectional study.
AB  - Background: Although several studies have identified risk factors for high blood
      pressure (BP), data from Afro-Caribbean populations are limited. Additionally,
      less is known about how putative risk factors operate in young adults and how
      social factors influence the risk of high BP. In this study, we estimated the
      relative risk for elevated BP or hypertension (EBP/HTN), defined as BP >= 120/80
      mmHg, among young adults with putative cardiovascular disease (CVD) risk factors
      in Jamaica and evaluated whether relative risks differed by sex. Methods: Data
      from 898 young adults, 18-20 years old, were analysed. BP was measured with a
      mercury sphygmomanometer after participants had been seated for 5 min.
      Anthropometric measurements were obtained, and glucose, lipids and insulin
      measured from a fasting venous blood sample. Data on socioeconomic status (SES)
      were obtained via questionnaire. CVD risk factor status was defined using
      standard cut-points or the upper quintile of the distribution where the numbers
      meeting standard cut-points were small. Relative risks were estimated using odds
      ratios (OR) from logistic regression models. Results: Prevalence of EBP/HTN was
      30% among males and 13% among females (p < 0.001 for sex difference). There was
      evidence for sex interaction in the relationship between EBP/HTN and some of risk
      factors (obesity and household possessions), therefore we report sex-specific
      analyses. In multivariable logistic regression models, factors independently
      associated with EBP/HTN among men were obesity (OR 8.48, 95% CI [2.64-27.2], p <
      0.001), and high glucose (OR 2.01, CI [1.20-3.37], p = 0.008), while high HOMA-IR
      did not achieve statistical significance (OR 2.08, CI [0.94-4.58], p = 0.069). In
      similar models for women, high triglycerides (OR 1.98, CI [1.03-3.81], p = 0.040)
      and high HOMA-IR (OR 2.07, CI [1.03-4.12], p = 0.039) were positively associated
      with EBP/HTN. Lower SES was also associated with higher odds for EBP/HTN (OR
      4.63, CI [1.31-16.4], p = 0.017, for moderate vs. high household possessions; OR
      2.61, CI [0.70-9.77], p = 0.154 for low vs. high household possessions). Alcohol
      consumption was associated with lower odds of EBP/HTN among females only; OR 0.41
      (CI [0.18-0.90], p = 0.026) for drinking <1 time per week vs. never drinkers, and
      OR 0.28 (CI [0.11-0.76], p = 0.012) for drinking >=3 times per week vs. never
      drinkers. Physical activity was inversely associated with EBP/HTN in both males
      and females. Conclusion: Factors associated with EBP/HTN among Jamaican young
      adults include obesity, high glucose, high triglycerides and high HOMA-IR, with
      some significant differences by sex. Among women lower SES was positively
      associated with EBP/HTN, while moderate alcohol consumption was associated lower
      odds of EBP/HTN.

PMID- 29456898
TI  - Passive Radar for Opportunistic Monitoring in E-Health Applications.
AB  - This paper proposes a passive Doppler radar as a non-contact sensing method to
      capture human body movements, recognize respiration, and physical activities in e
      Health applications. The system uses existing in-home wireless signal as the
      source to interpret human activity. This paper shows that passive radar is a
      novel solution for multiple healthcare applications which complements traditional
      smart home sensor systems. An innovative two-stage signal processing framework is
      outlined to enable the multi-purpose monitoring function. The first stage is to
      obtain premier Doppler information by using the high speed passive radar signal
      processing. The second stage is the functional signal processing including micro
      Doppler extraction for breathing detection and support vector machine classifier
      for physical activity recognition. The experimental results show that the
      proposed system provides adequate performance for both purposes, and prove that
      non-contact passive Doppler radar is a complementary technology to meet the
      challenges of future healthcare applications.

PMID- 29456899
TI  - Facial Weakness, Diplopia, and Fever in a 31-Year-Old: An Atypical Case of
      Tuberculous Meningitis.
AB  - Tuberculous meningitis (TBM) is an infection of the central nervous system (CNS)
      meninges that carries high morbidity and mortality. It is important to recognize,
      as patients may present with atypical symptoms. We describe the case of a 31-year
      old man with a history of diabetes who presented with a sub-acute onset of right
      sided facial weakness and right gaze difficulty with diplopia. History revealed
      low-grade fever, right-sided headache, fatigue and moderate weight loss for the
      past several weeks. The patient did not report neck stiffness, rigidity, fever,
      chills or cough. The physical exam revealed sixth nerve palsy with a right
      Horner's syndrome. Magnetic resonance imaging (MRI) of the brain showed
      pachymeningeal enhancement. A spinal tap revealed elevated white blood cells
      (WBCs), glucose and protein; cerebrospinal fluid (CSF) culture showed
      Mycobacterium tuberculosis. The patient was diagnosed with TBM and treated with
      isoniazid, rifampin, pyrazinamide, ethambutol and vitamin B6 for 12 months. The
      timely diagnosis of TBM can be challenging due to a nonspecific clinical
      presentation. In patients with a sub-acute onset of headache, fever and meningeal
      signs, TBM should be considered in the differential. If suspected, treatment
      should be initiated immediately to prevent further neurological impairment and
      death.

PMID- 29456900
TI  - A Barium Swallow Study Leading to an Incidental Finding on a Screening
      Colonoscopy.
AB  - Barolith is a mixture of firm feces with barium sulfate, and a frequent cause of
      obstruction of the appendiceal lumen that can result in appendicitis.
      Nonetheless, some other complications like aspiration, allergic reaction, and
      bowel obstruction have also been reported.  We present the case of a 71-year-old
      man with a history of amyotrophic lateral sclerosis (ALS), who came to the
      gastroenterology clinic complaining of intermittent loose stools and dysphagia to
      solids for the past months. The patient underwent a barium swallow study six days
      prior and was completely normal. A colonoscopy was done showing normal appearing
      mucosa, with a whitish foreign object found on the appendiceal orifice. Removal
      of the barolith was done by means of a biopsy forceps. Our patient did not have
      any signs or symptoms of appendicitis prior to the procedure, and the successful
      removal of the barolith was achieved. Elderly patients, and patients with
      decreased gastrointestinal (GI) transit, could be a population at risk for barium
      retention/appendicitis; for this reason, more research studies should be done to
      assess possible preventive treatments.

PMID- 29456901
TI  - Awake Craniotomy for the Treatment of a Cortical Pseudoaneurysm in a Pregnant
      Patient.
AB  - Neurosurgical pathologies presenting during pregnancy are uncommon. If present,
      the situation creates a unique diagnostic, observational, and therapeutic
      challenge as both lives are placed at potential risk. Surgical procedures during
      pregnancy are approached carefully as physiological stressors associated with
      surgery and anesthesia may cause fetal or maternal compromise. We present the
      only known case of a pseudoaneurysm treated with an awake craniotomy, allowing us
      to abate the risks associated with general anesthesia in pregnancy. A female
      suffered a superficially penetrating gunshot wound to the head for which she
      underwent a craniotomy with complete neurological recovery. She had complaints of
      intermittent headaches, dizziness, and tingling of her hands five months
      thereafter. The cerebral angiogram demonstrated an 8 mm pseudoaneurysm under her
      craniotomy site. A surgical repair of this aneurysm was undertaken in the 23rd
      week of pregnancy via an awake craniotomy with regional scalp block. The aneurysm
      was resected without complication, and the patient tolerated the procedure
      without neurological deficit during or subsequent to the operation.
      Cerebrovascular pathology in pregnant patients remains a difficult situation that
      poses challenges associated with the pathology itself as well as the anesthetic
      implications inherent with operative management. The neurosurgical literature
      demonstrates that surgical management of cerebrovascular pathology is well
      tolerated in pregnancy, and our case further demonstrates the capability of
      utilizing an awake craniotomy for the treatment of this type of lesion without
      causing a residual deficit.

PMID- 29456902
TI  - Review of Assessment Scales for Diagnosing and Monitoring Sports-related
      Concussion.
AB  - Sports-related concussion has emerged as a public health crisis due to increased
      diagnosis of the condition and increased participation in organized and
      recreational athletics worldwide. Under-recognition of concussions can lead to
      premature clearance for athletic participation, leaving athletes vulnerable to
      repeat injury and subsequent short- and long-term complications. There is
      overwhelming evidence that assessment and management of sports-related
      concussions should involve a multifaceted approach. A number of assessment
      criteria have been developed for this purpose. It is important to understand the
      available and emerging diagnostic testing modalities for sports-related
      concussions. The most commonly used tools for evaluating individuals with
      concussion are the Post-Concussion Symptom Scale (PCSS), Standard Assessment of
      Concussion (SAC), Standard Concussion Assessment Tool (SCAT3), and the most
      recognized computerized neurocognitive test, the Immediate Post-Concussion
      Assessment and Cognitive Testing (ImPACT). The strengths and limitations of each
      of these tools, and the Concussion Resolution Index (CRI), CogSport, and King
      Devick tests were evaluated. Based on the data, it appears that the most
      sensitive and specific of these is the ImPACT test. Additionally, the King-Devick
      test is an effective adjunct due to its ability to test eye movements and
      brainstem function.

PMID- 29456903
TI  - Winged Scapula: A Comprehensive Review of Surgical Treatment.
AB  - Winged scapula is caused by paralysis of the serratus anterior or trapezius
      muscles due to damage to the long thoracic or accessory nerves, resulting in loss
      of strength and range of motion of the shoulder. Because this nerve damage can
      happen in a variety of ways, initial diagnosis may be overlooked. This paper
      discusses the anatomical structures involved in several variations of winged
      scapula, the pathogenesis of winged scapula, and several historical and
      contemporary surgical procedures used to treat this condition. Additionally, this
      review builds upon the conclusions of several studies in order to suggest areas
      for continued research regarding the treatment of winged scapula.

PMID- 29456904
TI  - Felis Punctatis: Cat Claw-induced Punctures.
AB  - Animal-induced conditions in humans predominantly present as infectious zoonoses.
      However, trauma-associated injuries from the teeth or claws can also occur.
      Several zoonotic infections can be transmitted by cats, a common household pet,
      to their owners. The clinical features of a woman who developed multiple sites of
      trauma-induced cutaneous punctures from her cat's paws while it was kneading on
      her clothes-covered abdomen are described. The repetitive insertion and
      withdrawal of the sharp tips of the cat's claws created distinctive groups of
      erythematous punctures on the patient's skin. We suggest that Latin nomenclature
      be used to designate the name for this claw-induced dermatosis that includes not
      only the causative animal (felis for cat) but also a descriptive term for the
      skin lesions (punctatis for punctures): felis punctatis.

PMID- 29456905
TI  - A Comprehensive Review of the Sternal Foramina and its Clinical Significance.
AB  - A sternal foramen (SF), which arises from the incomplete fusion of the
      cartilaginous neonatal sternum, is a relatively common anatomical variation found
      in 2.5% to 13.8 % of all individuals. SFs are usually located at the lower third
      of the sternal body and their average diameter is 6.5 mm. An SF is subclinical;
      however, its close proximity to the thoracic organs, i.e., the heart and lungs,
      entails a risk of serious complications from blinded sternal interventions.
      Moreover, its presence can lead to misinterpretation of radiological and
      postmortem findings. The SF is ignored by many physicians and non-physician
      healthcare providers who must understand its clinical significance in order to
      optimize patient care. Our aim in this review is to highlight the potential
      clinical consequences for SF patients, discuss recommendations for performing
      sternal procedures safely when this anatomical variation is present, and preclude
      radiological and pathological misinterpretations so that patient care can be
      improved.

PMID- 29456906
TI  - Health Communication Experiences of Emerging Adults with Type 1 Diabetes.
AB  - Objective: In an effort to refine a model of clinical care identifying effective
      communication with health care providers (HCPs) as a key skill for successful
      transition to adult medical care, this study explored the perspectives of
      emerging adults with type 1 diabetes (T1D) about factors that impact the quality
      and content of communication with their HCPs. Methods: Twenty emerging adults
      with T1D were interviewed about health communication experiences with their
      pediatric HCP and readiness for transition to adult diabetes care. Interviews
      were recorded and transcribed; three raters coded transcripts using conventional
      content analysis for broad themes. Results: Five themes emerged from the data
      capturing factors that influence emerging adult-HCP communication: HCP
      interaction style, HCP consistency, HCP support for autonomy, parental
      involvement in medical care, and emerging adult comfort with disclosure. Most
      emerging adults had not discussed transition to adult diabetes care with their
      HCP; some expressed confidence in their ability to transition while others
      expressed anxiety about the transition process. Conclusions: Findings support the
      conceptual model of communication and inform clinical implications for working
      with emerging adults with T1D. Continuity of care should be prioritized with
      transition-age patients. Additionally, HCPs should initiate conversations about
      engagement in risky behaviors and transition to adult medical care and ensure
      emerging adults have time without parents to discuss these sensitive topics.
      Psychologists can enhance the transition process by facilitating effective
      patient-HCP communication and coaching both patients and HCPs to ask questions
      about risky behaviors and transition to adult medical care.

PMID- 29456908
TI  - Editorial.

PMID- 29456909
TI  - Comparing the 5-Year Health State Utility Value of Cervical Disc Replacement and
      Anterior Cervical Discectomy and Fusion.
AB  - Study Design: Health utility analysis. Objectives: To determine the health state
      utility (HSU) of 1- and 2-level anterior cervical discectomy and fusion (ACDF)
      and cervical disc replacement (CDR). Methods: Data from the Medtronic Prestige
      Cervical Disc investigational device exemption studies was used. Four groups were
      defined: 1-level ACDF, 1-level CDR, 2-level ACDF, and 2-level CDR. The 36-item
      Short Form Health Survey (SF-36) was collected at baseline, 12 months, 24 months,
      36 months, and 60 months postoperatively and converted into utility scores for
      each time point. A repeated-measures 1-way analysis of variance (ANOVA) was used
      to detect differences among groups. Tukey's method for multiple comparisons was
      used to determine which means within the groups were statistically different (P <
      .05). Results: We found a statistically significant difference in HSU among
      groups as determined by repeated-measures 1-way ANOVA (P = .0008). Post hoc
      analysis indicated that 1-level ACDF had a statistically lower utility score
      compared with 1- and 2-level CDR (P = .04 and P = .02, respectively). Similarly,
      2-level ACDF had lower utility values compared with 2-level CDR (P = .010). One
      level ACDF utility values were not different from 2-level ACDF values (P = .55).
      Similarly, 1-level CDR and 2-level CDR did not have different utility values (P =
      .67). Conclusions: Overall, CDR had higher health state utility scores for 1- and
      2-level procedures at every time point. This study indicates that CDR results in
      a higher postoperative health utility state than ACDF, and may therefore be an
      effective alternative to ACDF for treating degenerative conditions of the
      cervical spine.

PMID- 29456907
TI  - Nanoparticles in the environment: where do we come from, where do we go to?
AB  - Nanoparticles serve various industrial and domestic purposes which is reflected
      in their steadily increasing production volume. This economic success comes along
      with their presence in the environment and the risk of potentially adverse
      effects in natural systems. Over the last decade, substantial progress regarding
      the understanding of sources, fate, and effects of nanoparticles has been made.
      Predictions of environmental concentrations based on modelling approaches could
      recently be confirmed by measured concentrations in the field. Nonetheless,
      analytical techniques are, as covered elsewhere, still under development to more
      efficiently and reliably characterize and quantify nanoparticles, as well as to
      detect them in complex environmental matrixes. Simultaneously, the effects of
      nanoparticles on aquatic and terrestrial systems have received increasing
      attention. While the debate on the relevance of nanoparticle-released metal ions
      for their toxicity is still ongoing, it is a re-occurring phenomenon that inert
      nanoparticles are able to interact with biota through physical pathways such as
      biological surface coating. This among others interferes with the growth and
      behaviour of exposed organisms. Moreover, co-occurring contaminants interact with
      nanoparticles. There is multiple evidence suggesting nanoparticles as a sink for
      organic and inorganic co-contaminants. On the other hand, in the presence of
      nanoparticles, repeatedly an elevated effect on the test species induced by the
      co-contaminants has been reported. In this paper, we highlight recent
      achievements in the field of nano-ecotoxicology in both aquatic and terrestrial
      systems but also refer to substantial gaps that require further attention in the
      future.

PMID- 29456910
TI  - Comparing the Incidence of Index Level Fusion Following Minimally Invasive Versus
      Open Lumbar Microdiscectomy.
AB  - Study Design: Retrospective cohort study. Objectives: To determine the incidence
      of index level fusion following open or minimally invasive lumbar
      microdiscectomy. Methods: We conducted a retrospective review of 174 patients
      with a symptomatic single-level lumbar herniated nucleus pulposus who underwent
      microdiscectomy via a mini-open approach (MIS; 39) or through a minimally
      invasive dilator tube (135). Outcomes of interest included revision
      microdiscectomy and the ultimate need for index level fusion. Continuous
      variables were analyzed with independent sample t test, and chi2 analysis was
      used for categorical data. A multivariate regression analysis was performed to
      identify predictive factors for patients that required index level fusion after
      lumbar microdiscectomy. Results: There was no difference in patient demographics
      in the open and MIS groups aside from length of follow-up (60.4 vs 40.03 months,
      P < .0001) and body mass index (24.72 vs 27.21, P = .03). The rate of revision
      microdiscectomy was not statistically significant between open and MIS approaches
      (10.3% vs 10.4%, P = .90). The rate of patients who ultimately required index
      level fusion approached significance, but was not statistically different between
      open and MIS approaches (10.3% vs 4.4%, P = .17). Multivariate regression
      analysis indicated that the need for eventual index level fusion after lumbar
      microdiscectomy was statistically predicted in smokers and those patients who
      underwent revision microdiscectomy (P < .05) in both open and MIS groups.
      Conclusions: Our results suggest a low likelihood of patients ultimately
      requiring fusion following microdiscectomy with predictors including smoking
      status and a history of revision microdiscectomy.

PMID- 29456911
TI  - Correlation Between Lumbopelvic and Sagittal Parameters and Health-Related
      Quality of Life in Adults With Lumbosacral Spondylolisthesis.
AB  - Study Design: Secondary analysis of prospective, multicenter data. Objective: To
      evaluate impact of sagittal parameters on health-related quality of life (HRQoL)
      in adults with lumbosacral spondylolisthesis. Methods: Adults with unoperated
      lumbosacral spondylolisthesis were identified in the Spinal Deformity Study Group
      database. Pearson's correlations were calculated between SF-12 (Short Form
      12)/Scoliosis Research Society-30 (SRS-30) scores and radiographic parameters (C7
      sagittal vertical axis [SVA] deviation, T1 pelvic angle, pelvic tilt [PT], pelvic
      incidence, sacral slope, slip angle, Meyerding slip grade, Labelle
      classification). Main effects linear regression models measured association
      between individual health status measures and individual radiographic predictor
      variables. Results: Forty-five patients were analyzed (male, 15; female, 30;
      average age 40.5 +/- 18.7 years; 14 low-grade, 31 high-grade). For low-grade
      slips, SVA had strong negative correlations with SF-12 mental component score
      (MCS), SRS-30 appearance, mental, and satisfaction domains (r = -0.57, r = -0.60,
      r = -0.58, r = -0.53, respectively; P < .05). For high-grade slips, slip angle
      had a moderate negative correlation with SF-12 MCS (r = -0.36; P = .05) and SVA
      had strong negative correlations with SF-12 physical component score (PCS), SRS
      30 appearance and activity domains (r = -0.48, r = -0.48, r = -0.45; P < .05) and
      a moderate negative correlation with SRS-30 total (r = -0.37; P < .05). T1 pelvic
      angle had a moderate negative correlation with SF-12 PCS and SRS-30 appearance (r
      = -0.37, r = -0.36; P <= .05). For every 1 degrees  increase in PT, there was a
      0.04-point decrease in SRS appearance, 0.05-point decrease in SRS activity, 0.06
      point decrease in SRS satisfaction, and 0.04-point decrease in SRS total score (P
      < .05). Conclusion: Lumbosacral spondylolisthesis in adults negatively affects
      HRQoL. Multiple radiographic sagittal parameters negatively affect HRQoLs for
      patients with low- and high-grade slips. Improvement of sagittal parameters is an
      important goal of surgery for adults with lumbosacral spondylolisthesis.

PMID- 29456912
TI  - Dural Tears in Adult Deformity Surgery: Incidence, Risk Factors, and Outcomes.
AB  - Study Design: Retrospective cohort study. Objectives: Describe the rate of dural
      tears (DTs) in adult spinal deformity (ASD) surgery. Describe the risk factors
      for DT and the impact of this complication on clinical outcomes. Methods:
      Patients with ASD undergoing surgery between 2008 and 2014 were separated into DT
      and non-DT cohorts; demographics, operative details, radiographic, and clinical
      outcomes were compared. Statistical analysis included t tests or chi2 tests as
      appropriate and a multivariate analysis. Results: A total of 564 patients were
      identified. The rate of DT was 10.8% (n = 61). Patients with DT were older (61.1
      vs 56.5 years, P = .005) and were more likely to have had prior spine surgery
      (odds ratio [OR] = 2.0, 95% confidence interval [CI] = 1.2-3.3, P = .007). DT
      patients had higher pelvic tilt, lower lumbar lordosis, and greater pelvic
      incidence lumbar lordosis mismatch than non-DT patients (P < .05). DT patients
      had longer operative times (424 vs 375 minutes, P = .008), were more likely to
      undergo interbody fusions (OR = 2.0, 95% CI = 1.1-3.6, P = .021), osteotomies (OR
      = 2.2, 95% CI = 1.1-4.0, P = .012), and decompressions (OR = 2.3, 95% CI = 1.3
      4.3, P = .003). In our multivariate analysis, only decompressions were associated
      with an increased risk of DT (OR = 3.2, 95% CI = 1.4-7.6, P = .006). There were
      no significant differences in patient outcomes at 2 years. Conclusions: The rate
      of DT was 10.8% in an ASD cohort. This is similar to rates of DT reported
      following surgery for degenerative pathology. A history of prior spine surgery,
      decompression, interbody fusion, and osteotomies are all associated with an
      increased risk of DT, but decompression is the only independent risk factor for
      DT.

PMID- 29456914
TI  - Is Cervical Bracing Necessary After One- and Two-Level Instrumented Anterior
      Cervical Discectomy and Fusion? A Prospective Randomized Study.
AB  - Study Design: Prospective randomized control trial. Objective: To investigate the
      role of cervical collars in postoperative care following 1- and 2-level
      instrumented anterior cervical discectomy and fusion (ACDF). Methods: The
      Cervical Spine Research Society Resident Fellow Grant funded this project. Fifty
      consecutive patients undergoing 1- or 2-level ACDF surgery were randomized into
      groups receiving either no brace or a cervical brace for 6 weeks postoperatively.
      Neck Disability Index scores were recorded preoperatively and at regular follow
      up visits up to 1 year. Computed tomography scans were read 1 year
      postoperatively to determine fusion rates, and subsidence was measured as change
      in middle vertebral distance between initial postoperative and 6-month follow-up
      lateral cervical radiographs. Results: Twenty-two patients were in the no-brace
      group, and 22 patients were in the brace group at final follow-up, with an
      average age of 50 and 55 years, respectively. The no-brace group had a total of
      32 operative levels, whereas the brace group had 38 operative levels. There was
      no statistically significant difference in 1-year postoperative Neck Disability
      Index scores between the brace (9.30) and no-brace (6.95) groups (P = .28), in 6
      month subsidence of all operative levels between the brace (0.85 mm) and no-brace
      (0.79 mm) groups (P = .72), or in the proportion of fused levels between the
      brace (89%) and no-brace (97%) groups (P = .37). Conclusions: Our results suggest
      no advantage in wearing a cervical brace following 1- or 2-level ACDF surgery
      with respect to 1-year outcome scores, 1-year fusion rates, and 6-month
      subsidence.

PMID- 29456913
TI  - Investigating the 7-Year Cost-Effectiveness of Single-Level Cervical Disc
      Replacement Compared to Anterior Cervical Discectomy and Fusion.
AB  - Study Design: Cost-effectiveness analysis. Objectives: To determine the 7-year
      cost-effectiveness of cervical disc replacement (CDR) and anterior cervical
      discectomy and fusion (ACDF). Methods: We analyzed 7-year Short Form-36 Health
      Survey data collected from the Prestige Cervical Disc investigational device
      exemption study (IDE). The SF-6D algorithm was used to convert this data into
      health state utilities. Costs were calculated from the payer perspective, and
      quality adjusted life years (QALYs) were used to represent effectiveness. A
      Markov transition-state model was used to evaluate the cost-effectiveness of
      single-level CDR versus ACDF, and a Monte Carlo simulation was performed to
      assess the probabilistic sensitivity of the model. Results: CDR generated a 7
      year cost of $172 989 compared to a 7-year cost of $143 714 for ACDF. CDR
      generated 4.53 QALYs compared to 3.85 QALYs generated by ACDF. The cost
      effectiveness ratio of CDR was $38 247/QALY, while the cost-effectiveness ratio
      of ACDF was $37 325/QALY. The incremental cost-effectiveness ratio of CDR was $43
      522/QALY, under the willingness to pay threshold of $50 000/QALY. Our
      probabilistic sensitivity analysis demonstrated CDR would be chosen 56% of the
      time based on 10 000 simulations. Conclusions: Single-level CDR and ACDF were
      both cost-effective strategies at 7 years for treating degenerative conditions of
      the cervical spine. Both the Markov simulation and the Monte Carlo simulation
      demonstrate CDR to be the more cost-effective strategy at 7 years. Continued
      analysis of IDE data should be performed to validate long-term cost-effectiveness
      of these treatment strategies.

PMID- 29456916
TI  - Spine Degenerative Conditions and Their Treatments: National Trends in the United
      States of America.
AB  - Study Design: Retrospective database study. Objective: Low back and neck pain are
      among the top leading causes of disability worldwide. The aim of our study was to
      report the current trends on spine degenerative disorders and their treatments.
      Methods: Patients diagnosed with lumbar or cervical spine conditions within the
      orthopedic subset of Medicare and Humana databases (PearlDiver). From the initial
      cohorts we identified subgroups based on the treatment: fusion or nonoperative
      within 1 year from diagnosis. Poisson regression was used to determine
      demographic differences in diagnosis and treatment approaches. Results: Within
      the Medicare database there were 6 206 578 patients diagnosed with lumbar and 3
      156 215 patients diagnosed with cervical degenerative conditions between 2006 and
      2012, representing a 16.5% (lumbar) decrease and 11% (cervical) increase in the
      number of diagnosed patients. There was an increase of 18.5% in the incidence of
      fusion among lumbar patients. For the Humana data sets there were 1 160 495
      patients diagnosed with lumbar and 660 721 patients diagnosed with cervical
      degenerative disorders from 2008 to 2014. There was a 33% (lumbar) and 42%
      (cervical) increases in the number of diagnosed patients. However, in both lumbar
      and cervical groups there was a decrease in the number of surgical and
      nonoperative treatments. Conclusions: There was an overall increase in both
      lumbar and cervical conditions, followed by an increase in lumbar fusion
      procedures within the Medicare database. There is still a burning need to
      optimize the spine care for the elderly and people in their prime work age to
      lessen the current national economic burden.

PMID- 29456915
TI  - Short-Term Complications of Anterior Fixation of Odontoid Fractures.
AB  - Study Design: Retrospective study. Objective: Anterior fixation of odontoid
      fracture has been associated with high morbidity and mortality in small, single
      institution series. Identifying risk factors may improve risk stratification and
      highlight factors that could be optimized preoperatively. The objective of this
      study was to determine the 30-day complication rate following anterior fixation
      of odontoid fractures and to identify associated risk factors among patients in a
      large national database. Methods: Patients who underwent anterior fixation were
      identified in the American College of Surgeons National Quality Improvement
      Program database (ACS NSQIP) from 2007 to 2012. Patient demographics, medical
      comorbidities, perioperative complications, and postoperative complications up to
      30 days were analyzed by univariate and multivariate analysis. Results: Overall,
      103 patients met criteria for the study. The average age was 73.9 years and
      patients were predominantly white (85.4%). Cardiac comorbidity was common
      (66.0%), as were dependent functional status (14.6%) and bleeding disorders
      (13.6%). Complications occurred in 37.9% of patients, and mortality was high
      (6.8%). Age, white race, and history of bleeding disorders were independently
      predictive of complications in the multivariate analysis. The postoperative
      hospital stay was >5 days for 45.6% of patients. Conclusion: In a large,
      multicenter database study, anterior fixation of odontoid fracture was associated
      with high morbidity and mortality. Although advanced age was associated with
      increased risk of complications, patients undergoing anterior fixation were
      older, on average, than in prior studies. Bleeding disorder was a potentially
      modifiable risk factor for complications that could be optimized prior to
      surgery.

PMID- 29456917
TI  - Neuromonitoring in Spinal Deformity Surgery: A Multimodality Approach.
AB  - Study Design: Literature review. Objective: The aim of this study was to provide
      an overview of the available intraoperative monitoring techniques and the
      evidence around their efficacy in vertebral column resection. Methods: The
      history of neuromonitoring and evolution of the modalities are reviewed and
      discussed. The authors' specific surgical techniques and preferred methods are
      outlined in detail. In addition, the authors' experience and the literature
      regarding vertebral column resection and surgical mitigation of neurologic alarms
      are discussed at length. Results: Risk factors for signal changes have been
      identified, including preoperative neurologic deficit, severe kyphosis, increased
      curve magnitude, and significant cord shortening. Even though no evidence-based
      treatment algorithm exist for signal changes, strategies are discussed that can
      help prevent alarms and address them appropriately. Conclusion: Through
      implementation of multimodal intraoperative monitoring techniques, potential
      neurologic injuries are localized and managed in real time. Intraoperative
      monitoring is a valuable tool for improving the safety and outcome of spinal
      deformity surgery.

PMID- 29456919
TI  - Most Influential Literature in Spinal Tuberculosis: A Global Disease Without
      Global Evidence.
AB  - Study Design: Bibliometric review of the literature. Objective: This bibliometric
      analysis aims to give an overview of the most influential academic literature
      written on spinal tuberculosis. Methods: All databases included in the Thomson
      Reuters Web of Knowledge were searched for the most influential publications in
      spinal tuberculosis. The most cited articles published between 1950 and 2015,
      with the main focus on orthopedic surgery, were identified using a multistep
      approach, and a total of 100 articles were included. The publications were then
      analyzed in this bibliometric analysis. Results: The number of citations ranged
      from 243 to 36, with an average of 77.11. The articles were published in 34
      different journals, and the studies were conducted in 20 different countries. The
      top 3 countries, India, the United States, and China, published a total of 51% (n
      = 51) of all articles. Low-burden countries produced 60% (n = 60) of all articles
      in our list. African centers produced only 4% (n = 4) of all included articles.
      Conclusions: Indian and Chinese researchers dominate evidence in spinal
      tuberculosis. Other areas with high disease burden, such as Africa, do not
      feature. Most publications are retrospective studies with a low level of
      evidence.

PMID- 29456918
TI  - Cervical Disc Arthroplasty: A Comprehensive Review of Single-Level, Multilevel,
      and Hybrid Procedures.
AB  - Study Design: Systematic review. Objectives: Degenerative disc disease and
      spondylosis resulting in radiculopathy and retrodiscal myelopathy are among the
      most frequently encountered cervical spinal disorders. Traditionally, anterior
      cervical discectomy and fusion (ACDF) has successfully achieved neural
      decompression and restored intradiscal height in these conditions. Unfortunately,
      nonunion and iatrogenic adjacent segment pathology associated with fusion
      procedures in the cervical spine has led to an interest in motion-preserving
      procedures. Cervical disc arthroplasty (CDA) was developed in hopes of preserving
      cervical biomechanics while mitigating the complications associated with ACDF.
      Through a systematic review of both published and ongoing studies on single- and
      multilevel CDA, and hybrid surgeries, we aim to provide evidence for their safety
      and efficacy in the treatment of various cervical pathologies. Methods: A
      systematic search of several large databases, including Cochrane Central, PubMed,
      ClinicalTrials.gov, and the World Health Organization International Clinical
      Trials Registry was conducted to identify published studies and ongoing clinical
      trials on CDA and hybrid surgery. Results: Among the relevant studies reviewed, 3
      were randomized controlled trials, 2 systematic reviews, as well as multiple
      prospective case series, biomechanical studies, and meta-analyses. Conclusion:
      Over the past decade, multiple high-quality studies have shown that single-level
      CDA can offer equivalent clinical outcomes with a reduction in secondary
      procedures and total cost when compared to ACDF. However, more recently there has
      been an increasing prevalence of 2-level CDA and hybrid surgery. Although the
      data regarding these multilevel procedures is less robust, it appears that they
      may be as effective as their single-level counterparts.

PMID- 29456920
TI  - Evidence-Based Analysis of Adjacent Segment Degeneration and Disease After LIF: A
      Narrative Review.
AB  - Study Design: Narrative review. Objectives: The etiology of adjacent segment
      degeneration (ASDeg) and adjacent segment disease (ASDz) after lumbar interbody
      fusion (LIF) remains controversial. The aim of this narrative review was to
      provide an evidence-based analysis of the peer-reviewed literature on clinical
      studies of ASDeg and ASDz after LIF. Methods: A review was performed utilizing
      Medline, Embase, and Cochrane databases. Two reviewers independently extracted
      relevant data from each included study. Statistical comparisons were made when
      appropriate. Results: Nine articles that matched the inclusion and exclusion
      criteria were included. All the studies were Level III and retrospective. MINORS
      scores ranged from 9.5 to 13. Clinical outcomes were assessed in all 9 studies,
      but only 6 studies used validated outcomes measures. Only 6 studies reported
      values for both ASDeg and ASDz. ASDeg alone was reported in 3 studies. Due to the
      variability in the criteria for designation as ASDz (different radiographic
      modalities) and ASDeg (different outcomes measures), we were unable to calculate
      frequency-weighted mean values or compare the various surgical techniques.
      Conclusions: This review highlights the various limitations of the current
      literature on ASDeg and ASDz after lumbar fusion, specifically the absence of a
      rigorous definition and classification system and an extraordinary heterogeneity
      in methodology. There needs to be a fundamental shift in the current ASDeg and
      ASDz research landscape, toward a consensus, so that the high-level clinical
      research that is essential for treatment of spinal pathology may become
      available.

PMID- 29456921
TI  - Editorial Perspective.

PMID- 29456923
TI  - Response to the Letter to the Editor by Finsterer and Zarrouk-Mahjoub in Clin
      Nephrol Case Stud. 2018; 6: 1.
AB  - Not available.

PMID- 29456924
TI  - Unaccompanied Children Migrating from Central America: Public Health Implications
      for Violence Prevention and Intervention.
AB  - Purpose of Review: Unaccompanied children (UC) migrating to the USA from the
      Central American countries of El Salvador, Guatemala, and Honduras are an
      underserved population at high risk for health, academic, and social problems.
      These children experience trauma, violence, and other risk factors that are
      shared among several types of interpersonal violence. Recent Findings: The trauma
      and violence experienced by many unaccompanied children, and the subsequent
      implications for their healthy development into adulthood, indicate the critical
      need for a public health approach to prevention and intervention. Summary: This
      paper provides an overview of the violence experienced by unaccompanied children
      along their migration journey, the implications of violence and trauma for the
      health and well-being of the children across their lifespan, prevention and
      intervention approaches for UC resettled in the USA, and suggestions for adapted
      interventions to best address the unique needs of this vulnerable population.

PMID- 29456922
TI  - Propensity Scores in Pharmacoepidemiology: Beyond the Horizon.
AB  - Purpose of review: Propensity score methods have become commonplace in
      pharmacoepidemiology over the past decade. Their adoption has confronted
      formidable obstacles that arise from pharmacoepidemiology's reliance on large
      healthcare databases of considerable heterogeneity and complexity. These include
      identifying clinically meaningful samples, defining treatment comparisons, and
      measuring covariates in ways that respect sound epidemiologic study design.
      Additional complexities involve correctly modeling treatment decisions in the
      face of variation in healthcare practice, and dealing with missing information
      and unmeasured confounding. In this review, we examine the application of
      propensity score methods in pharmacoepidemiology with particular attention to
      these and other issues, with an eye towards standards of practice, recent
      methodological advances, and opportunities for future progress. Recent findings:
      Propensity score methods have matured in ways that can advance comparative
      effectiveness and safety research in pharmacoepidemiology. These include natural
      extensions for categorical treatments, matching algorithms that can optimize
      sample size given design constraints, weighting estimators that asymptotically
      target matched and overlap samples, and the incorporation of machine learning to
      aid in covariate selection and model building. Summary: These recent and
      encouraging advances should be further evaluated through simulation and empirical
      studies, but nonetheless represent a bright path ahead for the observational
      study of treatment benefits and harms.

PMID- 29456925
TI  - Continuity and change in local immigrant policies in times of austerity.
AB  - European cities are increasingly being recognised for the role they play in
      devising and implementing their own migration, integration and diversity
      policies. Yet very little is known about the local dimension of immigrant
      policymaking in crisis contexts. This introductory piece offers a rationale for
      analysing city-level immigrant policies in times of crisis and the salience of
      using crisis as a metaphor for the state of things, and outlines key scholarly
      works, debates, concepts and theories. It provides a range of historical and
      contemporary examples and considerations, and introduces an empirical city case
      study that is published as part of this mini-symposium. It argues that a crisis
      lens leads to a systematic understanding of local-level immigrant policymaking in
      recent and contemporary Western Europe. The mini-symposium's focus and findings
      should be relevant to both on-going academic and policy debates.

PMID- 29456926
TI  - Migration and child health in Moldova and Georgia.
AB  - There is scarce empirical evidence on the relation between migration and child
      health in Moldova and Georgia-two post-Soviet countries with large out-migration
      flows in the region. This study uses nationally representative data collected in
      2011-2012 in Moldova (N = 1601) and Georgia (N = 1193) to investigate how
      children's health associates with five transnational characteristics: migrant and
      return-migrant household types, parental migration and parental divorce, maternal
      and/or paternal migration and caregiver's identity, the duration of migration,
      and remittances. Findings show that, regardless of the transnational family
      setting, children of migrants have overall positive or no differing health
      compared to children in non-migrant households. However, significant gender
      differences are found in both countries. More often than not, Moldovan and
      Georgian girls are more at risk of having poorer health when living
      transnationally. These results add nuance to a field of research that has mainly
      emphasized negative outcomes for children in transnational care.

PMID- 29456927
TI  - Best practices in supervising cognitive behavioral therapy with youth.
AB  - Clinical supervision of cognitive behavioral therapy (CBT) with youth ensures
      better patient care and fosters trainees' professional development. However,
      often insufficient attention is directed toward disseminating best practices in
      supervision of CBT with youth. This Therapeutic Advances contribution aims to
      communicate the core content of supervision. Additionally, the key supervisory
      practices associated with CBT with youth are described. Supervisory outcomes are
      summarized and recommendations for supervisory practices are made.

PMID- 29456928
TI  - Behavioural and emotional disorders in childhood: A brief overview for
      paediatricians.
AB  - Mental health problems in children and adolescents include several types of
      emotional and behavioural disorders, including disruptive, depression, anxiety
      and pervasive developmental (autism) disorders, characterized as either
      internalizing or externalizing problems. Disruptive behavioural problems such as
      temper tantrums, attention deficit hyperactivity disorder, oppositional, defiant
      or conduct disorders are the commonest behavioural problems in preschool and
      school age children. The routine Paediatric clinic or Family Medicine/General
      Practitioner surgery presents with several desirable characteristics that make
      them ideal for providing effective mental health services to children and
      adolescents. DSM-5 and ICD-10 are the universally accepted standard criteria for
      the classification of mental and behaviour disorders in childhood and adults. The
      age and gender prevalence estimation of various childhood behavioural disorders
      are variable and difficult to compare worldwide. A review of relevant published
      literature was conducted, including published meta-analyses and national
      guidelines. We searched for articles indexed by Ovid, PubMed, PubMed Medical
      Central, CINAHL, EMBASE, Database of Abstracts and Reviews, and the Cochrane
      Database of Systematic reviews and other online sources. The searches were
      conducted using a combination of search expressions including "childhood",
      "behaviour", "disorders" or "problems". Childhood behaviour and emotional
      problems with their related disorders have significant negative impacts on the
      individual, the family and the society. They are commonly associated with poor
      academic, occupational, and psychosocial functioning. It is important for all
      healthcare professionals, especially the Paediatricians to be aware of the range
      of presentation, prevention and management of the common mental health problems
      in children and adolescents.

PMID- 29456929
TI  - Controversies in diagnosis and management of Kawasaki disease.
AB  - Kawasaki disease (KD) is a common medium vessel systemic vasculitis that usually
      occurs in small children. It has a predilection for the coronary arteries, but
      other medium sized arteries can also be involved. The etiology of this disorder
      remains a mystery. Though typical presentation of KD is quite characteristic, it
      may also present as incomplete or atypical disease in which case the diagnosis
      can be very challenging. As both incomplete and atypical forms of KD can be
      associated with serious coronary artery complications, the pediatrician can ill
      afford to miss these diagnoses. The American Heart Association has enunciated
      consensus guidelines to facilitate the clinical diagnosis and treatment of this
      condition. However, there are still several issues that remain controversial.
      Intravenous immunoglobulin remains the cornerstone of management but several
      other treatment modalities, especially glucocorticoids, are increasingly finding
      favour. We review here some of the contemporary issues, and the controversies
      thereon, pertaining to management of KD.

PMID- 29456930
TI  - Review of the evidence for the management of co-morbid Tic disorders in children
      and adolescents with attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is the most common
      neurodevelopmental disorder in children and adolescents, with prevalence ranging
      between 5% and 12% in the developed countries. Tic disorders (TD) are common co
      morbidities in paediatric ADHD patients with or without pharmacotherapy
      treatment. There has been conflicting evidence of the role of psychostimulants in
      either precipitating or exacerbating TDs in ADHD patients. We carried out a
      literature review relating to the management of TDs in children and adolescents
      with ADHD through a comprehensive search of MEDLINE, EMBASE, CINAHL and Cochrane
      databases. No quantitative synthesis (meta-analysis) was deemed appropriate. Meta
      analysis of controlled trials does not support an association between new onset
      or worsening of tics and normal doses of psychostimulant use. Supratherapeutic
      doses of dextroamphetamine have been shown to exacerbate TD. Most tics are mild
      or moderate and respond to psychoeducation and behavioural management. Level A
      evidence support the use of alpha adrenergic agonists, including Clonidine and
      Guanfacine, reuptake noradrenenaline inhibitors (Atomoxetine) and stimulants
      (Methylphenidate and Dexamphetamines) for the treatment of Tics and comorbid
      ADHD. Priority should be given to the management of co-morbid Tourette's syndrome
      (TS) or severely disabling tics in children and adolescents with ADHD. Severe TDs
      may require antipsychotic treatment. Antipsychotics, especially Aripiprazole, are
      safe and effective treatment for TS or severe Tics, but they only moderately
      control the co-occurring ADHD symptomatology. Short vignettes of different common
      clinical scenarios are presented to help clinicians determine the most
      appropriate treatment to consider in each patient presenting with ADHD and co
      morbid TDs.

PMID- 29456931
TI  - Abdominal obesity adversely affects bone mass in children.
AB  - AIM: To determine the effect of childhood obesity and insulin resistance on bone
      health. METHODS: We conducted a cross sectional study in pubertal adolescents and
      young adults 13-20 years old who were either overweight/obese or normal weight.
      Participants were Tanner 3 or above for pubertal stage, and had fasting blood
      work done to measure glucose, insulin, C-reactive protein and lipid levels.
      Homeostatic model of insulin resistance (HOMA-IR) was calculated using the
      formula (Fasting Blood Glucose *Insulin/405). Body composition and bone mineral
      density were measured using dual energy X-ray absorptiometry (DXA; Hologic QDR
      4500, Waltham, MA, United Kingdom). RESULTS: Percent trunk fat was associated
      inversely with whole body bone mineral content (BMC), whereas HOMA-IR was
      associated positively with whole body BMC. CONCLUSION: Our results suggest that
      abdominal adiposity may have an adverse effect on whole body bone parameters and
      that this effect is not mediated by insulin resistance.

PMID- 29456932
TI  - Neither hereditary periodic fever nor periodic fever, aphthae, pharingitis,
      adenitis: Undifferentiated periodic fever in a tertiary pediatric center.
AB  - AIM: To describe the frequency and clinical characteristics of patients with
      undifferentiated periodic fever (UPF) and to investigate whether a clinical
      classification of UPF based on the PRINTO-Eurofever score can help predicting the
      response to treatment and the outcome at follow-up. METHODS: Clinical and
      therapeutic information of patients with recurrent fever who presented at a
      single pediatric rheumatology center from January 2006 through April 2016 were
      retrospectively collected. Patients with a clinical suspicion of hereditary
      periodic fever (HPF) syndrome and patients with clinical picture of periodic
      fever, aphthae, pharingitis, adenitis (PFAPA) who were refractory to
      tonsillectomy underwent molecular analysis of five HPF-related genes: MEFV
      (NM_000243.2), MVK (NM_000431.3), TNFRSF1A (NM_001065.3), NLRP3 (NM_001079821.2),
      NLRP12 (NM_001277126.1). All patients who had a negative genetic result were
      defined as UPF and further investigated. PRINTO-Eurofever score for clinical
      diagnosis of HPF was calculated in all cases. RESULTS: Of the 221 patients
      evaluated for periodic fever, twelve subjects with a clinical picture of PFAPA
      who were refractory to tonsillectomy and 22 subjects with a clinical suspicion of
      HPF underwent genetic analysis. Twenty-three patients (10.4%) resulted negative
      and were classified as UPF. The median age at presentation of patients with UPF
      was 9.5 mo (IQR 4-24). Patients with UPF had a higher frequency of aphthae (52.2%
      vs 0%, P = 0.0026) and musculoskeletal pain (65.2% vs 18.2%, P = 0.0255) than
      patients with genetic confirmed HPF. Also, patients with UPF had a higher
      frequency of aphthous stomatitis (52.2% vs 10.7%, P < 0.0001), musculoskeletal
      pain (65.2% vs 8,0%, P < 0.0001), and abdominal pain (52.2% vs 4.8%, P < 0.0001)
      and a lower frequency of pharyngitis (56.6% vs 81.3%, P = 0.0127) compared with
      typical PFAPA in the same cohort. Twenty-one of 23 patients with UPF (91.3%)
      received steroids, being effective in 16; 13 (56.2%) were given colchicine, which
      was effective in 6. Symptoms resolution occurred in 2 patients with UPF at last
      follow-up. Classification according to the PRINTO-Eurofever score did not
      correlate with treatment response and prognosis. CONCLUSION: UPF is not a rare
      diagnosis among patients with periodic fever. Clinical presentation place UPF
      half way on a clinical spectrum between PFAPA and HPF. The PRINTO-Eurofever score
      is not useful to predict clinical outcome and treatment response in these
      patients.

PMID- 29456933
TI  - Pediatricians lack knowledge for the diagnosis and management of functional
      constipation in children over 6 mo of age.
AB  - AIM: To assess the knowledge of general pediatricians througout Indonesia about
      the diagnosis and treatment of childhood constipation. METHODS: A comprehensive
      questionnaire was distributed to general pediatricians from several teaching
      hospitals and government hospitals all over Indonesia. RESULTS: Data were
      obtained from 100 pediatricians, with a mean of 78.34 +/- 18.00 mo clinical
      practice, from 20 cities throughout Indonesia. Suspicion of constipation in a
      child over 6 mo of age arises when the child presents with a decreased frequency
      of bowel movements (according to 87% of participants) with a mean of one bowel
      movement per 3.59 +/- 1.0 d, hard stools (83%), blood in the stools (36%), fecal
      incontinence (33%), and/or difficulty in defecating (47%). Only 26 pediatricians
      prescribe pharmacologic treatment as first therapeutic approach, while the vast
      majority prefers nonpharmacologic treatment, mostly (according to 68%) The
      preferred nonpharmacologic treatment are high-fiber diet (96%), increased fluid
      intake (90%), toilet training (74%), and abdominal massage (49%). Duration of non
      pharmacological treatment was limited to 1 to 2 wk. Seventy percent of the
      pediatricians recommending toilet training could only mention some elements of
      the technique, and only 15% was able to explain it fully and correctly. Lactulose
      is the most frequent pharmacologic intervention used (87% of the participants),
      and rectal treatment with sodium citrate, sodium lauryl sulfo acetate, and
      sorbitol is the most frequent rectal treatment (85%). Only 51% will prescribe
      rectal treatment for fecal impaction. The majority of the pediatricians (69%)
      expect a positive response during the first week with a mean (+/- SD) of 4.1 (+/-
      2.56) d. Most participants (86%) treat during one month or even less. And the
      majority (67%) stops treatment when the frequency and/or consistency of the
      stools have become normal, or if the patient had no longer complaints.
      CONCLUSION: These data provide an insight on the diagnosis and management of
      constipation in childhood in Indonesia. Although general pediatricians are aware
      of some important aspects of the diagnosis and mangement of constipation, overall
      knowledge is limited. Efforts should be made to improve the distribution of
      existing guidelines. These findings highlight and confirm the difficulties in
      spreading existing information from guidelines to general pediatricians.

PMID- 29456934
TI  - Outcomes of transconjuctival sutureless 27-gauge vitrectomy for stage 4
      retinopathy of prematurity.
AB  - AIM: To report our initial experience with lens-sparing vitrectomy for stage 4
      retinopathy of prematurity using the 27-gauge (G) system. METHODS: This
      retrospective case series involved nine eyes of five babies with active stage 4
      ROP, who underwent 27-G lens-sparing vitrectomy. Surgery was done using 27-G
      valved cannulas and sclerotomies were made 1.5 mm from the limbus. Bilateral
      sequential vitrectomy was done in eight eyes. RESULTS: At one-year follow-up,
      anatomical outcome was favourable in all nine (100%) eyes. High-speed cutting and
      smaller sclerotomies were helpful in reducing the intra and post-operative
      complications. CONCLUSION: 27-G vitrectomy is well suited for stage 4 ROP
      surgeries.

PMID- 29456935
TI  - Radiological Evaluation of Cochlear Orientation and Its Implications in Cochlear
      Implantation.
AB  - To test whether there are variations in cochlear orientation with respect to age
      and sex, and its relevance in cochlear implant surgery. Implant otologists rely
      upon the anatomic landmarks including the facial recess and round window niche
      and round window membrane for accessibility and placement of electrode array into
      scala tympani of basal turn of cochlea. Anecdotally, surgeons note variations in
      cochlear orientation with respect to age. Cochlear orientation studied
      radiologically by pre-operative CT scan of temporal bone can guide a Surgeon's
      approach to cochlear implantation. To investigate the changes in cochlear
      orientation with respect to age and sex; and its relevance in cochlear
      implantation. A retrospective analytical study was performed on CT scans of
      temporal bones in patients (of our hospital from July 2013 to January 2015 i.e.
      for a period of 18 months) with no congenital or radiological abnormalities of
      cochlea. The basal turn angulations of cochlea varied with age and majority of
      change occurred during early age. The basal turn angulations of cochlea in
      difficult situations during cochlear implantation were correlated with the data.
      There is a significant variation in cochlear orientation as measured
      radiologically by basal turn angulations relative to midsagittal plane. The more
      obtuse and acute basal turn angulations have implications like difficulty in
      cochleostomy and electrode placement during cochlear implantation.

PMID- 29456936
TI  - Bone Metastases in Follicular Carcinoma of Thyroid.
AB  - Though the association between follicular carcinoma and bone metastasis is well
      established, the site-wise distribution is not known. One hundred seventy-three
      patients of follicular carcinoma presenting between 2003 and 2011 were selected
      from 1093 patients of follicular lesions presenting at a single institution. Of
      these, 59 (34%) with bone metastasis were included in the study. Fifty of the 59
      patients (84.7%) had metastasis at presentation, while 9 developed bone
      metastasis during follow-up. Sixty-one percent had solitary metastasis, 15
      (25.4%) had multiple bone involvement, while 8 patients (13.6%) had synchronous
      lung metastasis. Overall, the spine was the commonest site of bone metastases,
      seen in 20 patients (33.9%), followed by the pelvis, skull, long bones and
      sternum. Bone metastasis is a known phenomenon in follicular carcinoma. The spine
      is the commonest site followed by the pelvis.

PMID- 29456937
TI  - To Evaluate and Compare the Result of Ossiculoplasty Using Different Types of
      Graft Materials and Prosthesis in Cases of Ossicular Discontinuity in Chronic
      Suppurative Otitis Media Cases.
AB  - Chronic suppurative otitis media, with and without cholesteatoma, frequently
      results in disruption of the ossicular chain. The present study was designed to
      compare the outcome using autologous ossicle and titanium prosthesis in two
      groups of suitable patients presenting with chronic suppurative otitis media for
      middle ear reconstructive surgeries. A prospective study done from July 2012 to
      December 2013, at Mahatma Gandhi Medical College and Hospital, Sitapura, Jaipur
      (Rajasthan). The target group included patients with chronic suppurative otitis
      media admitted and planned for reconstructive middle ear surgery. The study group
      patients among the target group requiring certain ossicular reconstruction. The
      patients included were patients with CSOM with or without cholesteatoma in which
      there was ossicular discontinuity. The patients were divided in two groups A and
      B. In group A patients autologous incus was used and in group B titanium
      prosthesis either TORP or PORP was used for ossicular replacement. Out of 340
      patients as target group, 88 patients were included in study group. Further 88
      patients of study group, 51 patients were included in group A; rest 37 patients
      were included in group B. In group B patients partial ossicular replacement
      platinum prosthesis was used in 31 patients while in rest 6 patients a total
      ossicular replacement prosthesis was used. Out of 88 patients, 79 were primary
      cases and 9 were revision cases. Pre and post operative air bone gap were noted.
      Pre operatively both of the groups were identical in relation to air-bone gap.
      The postoperative air-bone gap was calculated as the difference between
      postoperative air conduction and preoperative bone conduction. On comparison of
      preoperative and post-operative hearing results there was improvement in air
      conduction threshold and air bone gap in both the groups. Post operatively
      difference in air bone gap closure between group A and group B was found
      statistically significant (P value = 0.032) suggesting better hearing outcomes
      after using titanium ossicular replacement prosthesis. On comparing partial or
      total ossicular replacement prosthesis no significant difference was found for
      the audiological outcome (P = 0.434). Various prognostic factors were also noted
      for air bone gap closure. Titanium ossicular replacement prosthesis have better
      outcome, and no significant difference found in audiological outcome for TORP and
      PORP.

PMID- 29456938
TI  - Deep Neck Space Infections-A Study in Diabetic Population in a Tertiary Care
      Centre.
AB  - This study is intended to analyze the clinical profile and outcomes of deep neck
      space infection in diabetic patients in our tertiary care centre. A prospective
      study of 1 year duration from 30th September 2015 to 30th September 2016 at
      department of Otorhinolaryngology, Gauhati Medical College and Hospital,
      Guwahati. A total of 45 diabetic patients who presented with DNSI are included in
      this study. Their demographic profile, etiology, bacteriology, treatment,
      duration of hospital stay, complications and outcomes have been analyzed. 45
      patients were recorded; 32 (71.11%) were men, and 13 (45%) were women, with a
      mean age of 63.27 +/- 7.55 years. There were 30 patients (66.67%) who had
      associated systemic diseases apart from diabetes mellitus. The parapharyngeal
      space in 13 patients (28.89%) was the most commonly involved space. Odontogenic
      infections in 18 patients (40%) and upper airway infections 9 patients (20%) were
      the two most common causes. Klebsiella pneumonia in 29 patients (64.44%), was the
      commonest organism isolated through pus cultures. All the patients except one
      (97.78%) came with abscess and underwent surgical drainage. One patient (2.22%)
      with carbuncle underwent regular dressing. Six patients (13.33%) had major
      complications. Those patients with other underlying systemic diseases or
      complications tended to have a longer hospital stay and were older. No cases of
      death has been reported. (mortality rate, 0%). DNSI patients with diabetes have a
      more severe clinical course. They are likely to have complications more
      frequently and a longer duration of hospital stay. In clinical practices while
      dealing with these patients more vigilance is required. On admission empirical
      antibiotics should cover K. pneumonia. Early surgical drainage remains the main
      method of treatment. Primary prevention can be achieved by orodental hygiene,
      regular dental check ups and in this part of the country by avoidance of
      substance abuse like tobacco chewing.

PMID- 29456939
TI  - Outcomes of Bone Anchored Hearing Aid Implant at Universiti Kebangsaan Malaysia
      Medical Centre (UKMMC).
AB  - The cross sectional study was conducted in Universiti Kebangsaan Malaysia Medical
      Center (UKMMC), Malaysia from August 2012 to December 2013. All patients
      implanted with in UKMMC from December 2001 until December 2012 was included.
      Glasgow Benefit Inventory (GBI) questionnaires and UKMMC questionnaires were used
      as part of the assessment tool. The GBI is a scoring which measures the change in
      health status produced by surgical interventions. UKMMC questionnaires was
      invented by our department to assess questions related to social and life style
      of patients and also the cosmetic perspective Baha implant and other daily
      related activities. The audiological assessment was assessed using hearing aid
      gain threshold. Complication with regards to skin reaction was graded using
      Holger Skin Classification. A total of 40 patients underwent Baha implant were
      recruited but only 35 patients fulfilled the criteria and included in this study
      for analysis. Age of patients ranged from 5 year old to 38 year old, with median
      of 13 years old. There were 22 patients (62.8%) were male and 13 patients (37.1%)
      were females. Almost all cases were canal atresia except one adult patient was a
      case of bilateral chronic discharging ear with chronic irritation with ear mould.
      Majority of patients 21 (60%) have hearing level of moderate to severe hearing
      loss (40-89 dB) and 14 patients (40%) have mild to moderate hearing loss (20-39
      dB). The level of hearing was retested post operatively. All of the patients have
      improvement in their aided hearing with the range of 10-25 dBL which is
      statistically significant at p value of <0.05. The GBI was scored positively in
      all subscales. Majority of patients (91.4%) used BAHA more than 4 h per day and
      88.6% agreed that BAHA is cosmetically acceptable. All patients experienced some
      form of skin irritation (Holger grade 1-2) however only 20% required surgical
      intervention. All our patients have range of 10-25 dB improvement of their aided
      hearing which is statistically significant at p value of <0.05. BAHA has been
      proven to show significant benefit in audiological improvement and quality of
      life.

PMID- 29456940
TI  - Mrmc Neo Surgical Ventilating Port and Neo Attic Malleo-Incudal Complex in
      Endoscopic Management of Limited Attico-Antral Cholesteatoma.
AB  - To study functional outcome of the endoscopic management of limited attico-antral
      cholesteatoma in terms of visualization of sac, cholesteatoma disease clearance,
      ABG closure improvement, preservation of residual anatomy and recurrence of
      disease. It is a prospective study done during Feb 2016 to March 2017 done on 20
      pts with limited attico-antral cholesteatoma with CT confirmation. Endoscopic
      management of limited attico-antral cholesteatoma with complete removal of sac,
      infected discharge and granulations along with creation of MRMC Neo surgical
      ventilating port (joining Anterior & posterior isthmuses) done in cases where
      residual attic anatomy was present to establish physiological attic ventilation
      and drainage. Whereas in cases of attic and ossicular erosion, ossiculoplasty
      along with neo attic malleo-incudal complex (with composite tragal cartilage with
      perichondrium graft) for lateral attic wall reconstruction was done to prevent
      attic retraction. Patients had mean pre op ABG of 36.29 +/- 6.29 and mean post op
      ABG closure of 16.33 +/- 6.50 with no recurrence of cholesteatoma at 6 months of
      follow up. Patient showed significant (55%) improvement in hearing with all
      having graft uptake in which four cases having mild pars tensa retraction which
      recovered later without any intervention. Thus creation of new MRMC Neo surgical
      ventilating port or neo attic malleo-incudal complex with endoscopic approach
      allows better visual access to clear the limited attico-antral disease with
      sparing of normal residual attic anatomy along with physiological ventilation and
      drainage having better hearing results and outcome.

PMID- 29456941
TI  - The Learning Curve in Surgical Practice and Its Applicability to Rhinoplasty.
AB  - The learning curve as a concept has been considered, discussed and debated in
      medical education and healthcare for over two decades. The precise usage has been
      recognised in surgical disciplines both broad specialties and sub-specialties.
      Rollin Daniel in his book stated that, rhinoplasty is the most difficult of all
      cosmetic operations for three reasons, (a) nasal anatomy is highly variable, (b)
      the procedure must correct form and function and (c) the final result must meet
      the patients expectations. With this in mind a study was carried on the
      perception of learning curve in rhinoplasty based on a surgeon questionnaire at
      Marien Hospital, Stuttgart, Germany under Prof. Gubisch. Aims of the study were,
      (1) to extract the perception of learning curve of Rhinoplasty from surgeons
      across a spectrum of experience, i.e. less experienced to experienced, (2) To
      calculate the perception of learning curve in rhinoplasty as for other surgical
      procedures i.e. minimum number, interquartile range, surgical time, accelerators,
      (3) To chart-out a road-map for a novice rhinoplasty surgeon for continued
      improvement in surgical skills and ability. The conclusion derived was the
      concept of learning curve in rhinoplasty cannot be applied to the operation of
      Septo-Rhinoplasty as a whole because the two factors i.e. interquartile range and
      minimum number to achieve proficiency have a wide range and cannot be
      generalized. It is thought that each type of Rhinoplasty should be dealt with
      separately and learning curve calculated accordingly, i.e. hump reduction,
      crooked nose and augmentation rhinoplasty.

PMID- 29456942
TI  - Bacterial Biofilms in Chronic Rhinosinusitis and Their Implications for Clinical
      Management.
AB  - To study the microbiological profile in patients with chronic rhino-sinusitis. To
      correlate disease severity with the presence of biofilms and host risk factors.
      To assess outcome of Sinus Surgery 2 weeks post operatively in terms of presence
      of bacteria and their ability to form biofilm. Prospective study. 50 cases of
      chronic rhino-sinusitis requiring Functional Endoscopic Sinus Surgery admitted in
      SDM Hospital, Dharwad, Karnataka were studied using intra-operative mucosal
      samples for microbiological analysis. The organisms isolated were tested for
      biofilm forming ability using three in vitro tests. Severity of disease was
      assessed using SNOT 22 scoring system. Of 50 cases studied, 66% showed presence
      of chronic rhino-sinusitis with polyposis and had higher SNOT scores compared to
      those without polyps. Bacterial isolates were obtained from only 17 samples.
      Staphylococcus species was isolated from 16 samples and Klebsiella pneumoniae
      from one. 11 Staph spp. isolates showed biofilm forming ability in vitro.
      Postoperative events in 3 cases yielded biofilm-forming Staphylococcus.
      Staphylococcus was the most dominant organism isolated and 11 isolates were
      biofilm formers. Thus the detection of biofilm forming organisms can be
      considered as a negative prognostic indicator and should forewarn the surgeon
      about the risk of recurrence.

PMID- 29456943
TI  - Transnasal Endoscopic Optic Nerve Decompression in Post Traumatic Optic
      Neuropathy.
AB  - To quantify the successful outcome in patients following optic nerve
      decompression in post traumatic unilateral optic neuropathy in form of
      improvement in visual acuity. A prospective study was carried out over a period
      of 5 years (January 2011 to June 2016) at civil hospital Ahmedabad. Total 20
      patients were selected with optic neuropathy including patients with direct and
      indirect trauma to unilateral optic nerve, not responding to conservative
      management, leading to optic neuropathy and subsequent impairment in vision and
      blindness. Decompression was done via Transnasal-Ethmo-sphenoidal route and
      outcome was assessed in form of post-operative visual acuity improvement at 1
      month, 6 months and 1 year follow up. After surgical decompression complete
      recovery of visual acuity was achieved in 16 (80%) patients and partial recovery
      in 4 (20%). Endoscopic transnasal approach is beneficial in traumatic optic
      neuropathy not responding to steroid therapy and can prevent permanent disability
      if earlier intervention is done prior to irreversible damage to the nerve.
      Endoscopic optic nerve surgery can decompress the traumatic and oedematous optic
      nerve with proper exposure of orbital apex and optic canal without any major
      intracranial, intraorbital and transnasal complications.

PMID- 29456944
TI  - Choanal Atresia: Birth Without Breath.
AB  - Bilateral Choanal atresia is a medical emergency. Corrective surgery is the
      mainstay of the treatment. Hegar's dilator was used in all cases to break the
      bony/membranous atretic plate. The 22 cases of choanal atresia all operated by
      the first author were included in this study. Eight cases were 1-5 year old with
      bilateral choanal atresia and all required immediate surgery as they had repeated
      attacks of respiratory distress and cycle of cyanosis. Eight cases were of CHARGE
      Syndrome. All the cases were operated under general anaesthesia. Hegar's dilators
      were used and nasal stents were placed in all cases. Although complete nasal
      patency was achieved by surgery, in 8 cases, neonates could not survive due to
      the CHARGE Syndrome. The mortality was unrelated to the surgery. The 14 cases
      which were not related to CHARGE Syndroma had a good postoperative recovery. 3
      cases were above 15 years old with unilateral complete bony/membranous choanal
      atresia and they presented with continuos nasal discharge. Hegar's dilators are a
      safe and simple method of surgery for choanal atresia. Nasal stenting is
      mandatory to prevent restenosis.

PMID- 29456945
TI  - Audiological Profile in Primary Sjogren's Syndrome in a Tertiary Care Setting and
      its Clinical Implications.
AB  - This study aims to assess the frequency and the profile of hearing loss among
      patients with primary Sjogren's syndrome in a tertiary care hospital in India and
      to look for an association between hearing loss and immunological parameters
      (anti-SSA antibody, anti-SSB antibody, anticardiolipin antibodies, complements C3
      and C4). This prospective observational study was done from January 2011 to
      October 2011 on consecutive patients diagnosed with primary Sjogren's syndrome in
      our tertiary care hospital. All patients underwent a puretone audiogram,
      tympanogram and acoustic reflex testing. The results of the tests were correlated
      with clinical and immunological findings. The frequency of audiometrically
      confirmed hearing loss in primary Sjogren's syndrome was estimated to be 78.38 %,
      though only 17.24 % complained of hearing loss; minimal to mild sensorineural
      hearing loss were the most common varieties. The commonest finding on
      tympanometry was 'A' type curve and acoustic reflex was absent in 18.92 % of
      cases. There was no association between hearing loss and age, sicca symptoms,
      systemic symptoms or immunological test results in primary Sjogren's syndrome.
      There was a high prevalence of hearing loss among patients with primary Sjogren's
      syndrome, but most patients were unaware of this. Hearing assessment and regular
      monitoring of hearing thresholds is advisable for all patients with primary
      Sjogren's syndrome.

PMID- 29456946
TI  - Detection of Epstein-Barr and Human Papilloma Viruses in the Middle Ear Squamous
      Cell Carcinoma.
AB  - The uncommon ear tumor of middle ear squamous cell carcinoma (MESCC) is thought
      to be associated with the history of long-term chronic otitis media in the most
      cases. The main etiologic factor of MESCC is still unclear and may be
      multifactorial. Infections of Epstein-Barr virus (EBV) and Human Papillomavirus
      (HPV) are considered as one of the etiologic factor of MESCC. Previous studies
      have shown that the EBV and HPV have been detected in MESCC. Although the EBV and
      HPV have been implicated in human malignancies, their roles in pathogenesis of
      MESCC have not been elucidated. There has never been report on the presence of
      EBV and HPV in Indonesian MESCC. This study aimed to determine the presence of
      EBV and HPV in MESCC. Seven paraffin-embedded tissues of speciment from biopsy
      were analyzed for the presence of EBV and HPV by immunohistochemistry, stained
      using polyclonal antibody anti EBNA1 and anti HPV. The samples consisted of 4 (57
      %) males and 3 (43 %) females with age range of 26-87 years old.
      Immunohistochemistry result demonstrated that EBV was detected in three of seven
      (43 %) and HPV in two of seven (29 %) samples. Coexistence of the presence of EBV
      and HPV were found in one of seven (14 %) sample. The presence of EBV and HPV in
      MESCC suggests that viral infection may play an important etiologic role in the
      carcinogenesis of middle ear.

PMID- 29456947
TI  - Aesthetic and Functional Evaluation of Total Nasal Reconstructions.
AB  - The loss of a portion or the totality of the nose has great relevance on the
      perception of the beauty of a face and can result in a catastrophic quality of
      life impairment. Several surgical techniques are currently available for the
      reconstruction of the nasal pyramid. However, there are very few nasal
      reconstruction quality evaluation protocols that allow the surgeon to choose
      objectively the best technique for each kind of defects. Six total nasal
      reconstruction performed in University of Sassari Maxillofacial Unit were
      evaluated with a protocol that investigate objectively and subjectively the
      surgical aesthetic and functional outcome. Sensitivity recovery on the
      reconstructive flaps was also assessed. Patients reported a satisfactory nasal
      reconstruction both functionally and aesthetically. Sensitivity recovery on the
      forehead flap was always present even after pedicle resection or in case of
      traumatic section of the infraorbital nerve. The use of a three layer
      reconstruction has proved a viable technique both aesthetically and functionally.
      In particular the use of the forehead flap to reconstruct the outer layer of the
      nose allows to carry a tissue with very similar characteristics to the original
      with a recovery of the sensitivity almost complete.

PMID- 29456948
TI  - Is Routine Use of High Resolution Computerized Tomography of Temporal Bone in
      Patients of Atticoantral Chronic Suppurative Otitis Media without Intracranial
      Complications Justified?
AB  - Role of high resolution computerized tomography (HRCT) of temporal bone is
      established in cases of atticoantral chronic suppurative otitis media (CSOM) with
      intracranial complications. Routine use of HRCT in management of patients of
      atticoantral CSOM without intracranial complications has been an issue of debate.
      The aim of this study was to evaluate the routine use of HRCT of temporal bone in
      such cases. This study was a prospective study done at LG hospital, AMC MET
      Medical College, Ahmedabad to evaluate and compare the temporal bone findings in
      HRCT and intraoperative findings in 100 patients with atticoantral CSOM. All
      patients underwent HRCT screening followed by surgical exploration of middle ear
      cleft. In extent of disease HRCT showed very high sensitivity and specificity for
      epitympanum (100, 94%) and mesotympanum (98, 98%) areas. It gave valuable
      information of disease extent in hidden areas like sinus tympani and facial
      recess of mesotympanum. HRCT satisfactorily delineated malleus and incus erosion
      but had 75% sensitivity for detecting erosion of stapes suprastructure, though
      specificity was of 97%. For bony anatomical landmarks HRCT showed very high
      sensitivity and specificity for detecting erosion of lateral semicircular canal,
      tegmen tympani and sinus plate. Detection of facial canal erosion on HRCT had
      moderate sensitivity of 75%. We concluded that routine use of HRCT is justified
      as a reliable preoperative tool in patients with atticoantral CSOM without
      intracranial complications and it helps to plan type of surgical intervention.
      HRCT has limited role to distinguish between granulations and cholesteatoma and
      also to delineate stapes supra structure and facial nerve canal.

PMID- 29456949
TI  - Clarithromycin in the Management of Chronic Rhinosinusitis: Preliminary Results
      of a Possible Its New Use.
AB  - The aim of this study is to evaluate the efficacy and safety of prolonged therapy
      with low-dose clarithromycin in patients with chronic rhinosinusitis with polyps
      (CRSwP) after endoscopic sinus surgery (ESS). A total of 10 patients with CRSwP
      were identified and subjected to bilateral ESS. In post-operative patients they
      were treated with nasal wash with saline solution and steroid sprays
      (beclomethasone). During follow-up, after 30-40 days after the operation (M =
      35.4 SD = +4.33), patients reported a worsening of symptoms with onset of nasal
      obstruction; reduction/loss of smell; headache; onset of viscous secretions and
      therefore all patients continued therapy with saline nasal irrigation, topical
      steroid therapy and started macrolide (clarithromycin 500 mg/pill: 1 pill/day for
      3 days a week for 1 month). 22-item SinoNasal Outcome Test (SNOT-22) and a score
      to the endoscopic evaluation (endoscopic appearance score, EAS) before and after
      treatment were performed to evaluate efficacy of treatment. The results of the
      SNOT-22 and EAS showed statistically significant improvements (p < 0.05) for some
      parameters such as: the need to blow nose, sneezing, hyposmia, viscous mucous
      secretions about the SNOT-22 and reduction of secretions and edema of the nasal
      mucosa about the EAS. The preliminary results of our study show that the low-dose
      clarithromycin for a period of 1 month can improve patient complaints with CRSwP
      not only through the antibacterial properties but also for the immunomodulatory
      characteristics.

PMID- 29456950
TI  - Cerebrospinal Fluid Leakage During Temporal Bone Surgery: Selecting Intra
      operative Dural Closure with a Dumbbell-Shaped Muscle Graft as a Surgical
      Approach.
AB  - Cerebrospinal fluid (CSF) leakages of the temporal bone may arise during mastoid
      surgery. The leakages can have multiple potential etiologies, for instance, using
      a cutting burr near the bony tegmen or monopolar electrocautery on the surface of
      the dura mater. In this paper, we introduced an effective and simple technique
      for the management of CSF leakages of the temporal bone. In a prospective case
      series, 36 patients (16 males and 20 females) who have had an experience of
      incidental or inevitable CSF otorrhea or otorhinorrhea during temporal bone
      surgery were selected. All patients were treated using a muscle graft in a
      dumbbell-shaped design through the dura defect at the Amir-Alam University
      Hospital between April 2005 and November 2008. The mean size of the defects was 5
      mm (a range of 2-10 mm). A dumbbell-shaped autologous muscle graft was
      immediately successful in sealing the leakage in all patients. Only five patients
      (13.8%) had some evidence of leakage remaining on the day after the operation,
      which was subsequently resolved by conservative management in four of them
      (11.1%). Only one patient (2.7%) was subjected to a second operation for a new
      defect. Recurrence of CSF leakage or other related complications were not
      observed during about 7 years of follow up. A free autologous muscle graft, using
      the dumbbell technique through a small to moderate dura defect is an effective,
      easily performed, and safe method to seal iatrogenic leakages of the temporal
      bone.

PMID- 29456951
TI  - Endoscopic Endo-Nasal Trans-Sphenoidal Excision of Pituitary Tumors: An
      Institutional Experience.
AB  - To analyze the clinical presentation, management and outcomes of patients with
      pituitary adenoma treated by Endoscopic Endo-nasal Trans-sphenoidal (EETS)
      excision. Study was conducted on the basis of medical records of 14 patients who
      had undergone EETS excision of pituitary adenomas. The data obtained was assessed
      for demographic and clinical characteristics, radiographic features and post
      operative outcomes. Study included 10 males and 4 females. Mean age of patients
      was 46.43 years (range 16-70 Years). Most common presentation was diminished
      vision reported in 79% patients. Features of acromegaly encountered in 21% cases.
      Location of majority of tumors was sellar with supra-sellar extension (71%)
      followed by sellar (14%), sellar with para-sellar extension (7%) and sellar with
      supra-sellar and para-sellar extensions (7%). Total tumor resection was achieved
      in 64% cases and sub-total resection in 36% cases. One of the lesions on biopsy
      revealed granulomatous pathology. No post-operative complication was seen in 71%
      patients. Transient Diabetes Insipidus was observed in 21% cases that resolved
      within 3-4 days. One patient expired due to meningitis and septicemia. One
      patient had CSF leak that was effectively managed by placing lumbar drain. There
      was significant improvement in visual symptoms and hormonal levels. Average
      hospital stay was 13.54 days and mean follow up period was 13 months. EETS
      approach is safe, minimally invasive and effective surgical technique for
      resection of pituitary adenomas with low post-operative morbidity, reduced
      hospital stay and better remission of symptoms.

PMID- 29456952
TI  - Clinicopathological Significance of Tumor Lymphatic Vessel Density in Head and
      Neck Squamous Cell Carcinoma.
AB  - Various studies have demonstrated that the lymphatic system is the additional
      route for solid tumor metastasis. Lymph nodes metastasis in Head and neck
      squamous cell carcinoma (HNSCC) is a major prognostic indicator for disease
      progression and a guide for therapeutic strategies. We conducted a study to
      compare intratumoral (IT) and peritumoral (PT) lymphatic vessel density (LVD) in
      HNSCC using lymphatic marker D2-40 and its correlation with lymph node
      metastasis, histological grading and other clinicopathological parameters. Fifty
      specimen of HNSCC with modified radical neck dissection tissue were included in
      the study group. Tissue from tumor, peritumoral tissue, tumor margin and all the
      lymph nodes were processed for paraffin wax blocks and histopathological
      diagnosis. Immunohistochemical profile of lymphatic vessels in intratumoral and
      peritumoral tissue was assessed by subjecting one section each from the tumor and
      peritumoral tissue to D2-40 immunostain. To determine LVD, four fields with the
      highest LVD (hot spots) were identified. The mean values were calculated by
      taking an average of all the measurements. The comparison of LVD between
      peritumoral and intratumoral area revealed significantly higher PT-LVD (P =
      0.001). No significant association was seen between LVD, IT-LVD and PT-LVD and
      different age groups, gender, site of tumor, risk factors, size of tumor, tumor
      inflammation, pushing/infiltrating margin and stage of tumors. Significantly
      higher LVD, IT-LVD and PT-LVD was seen in association with lymph node metastasis.
      Both high intratumoral and peritumoral LVD were found significantly associated
      with the presence of lymph node metastasis, however lymphatic vessels were found
      to be significantly more numerous and larger in peritumoral areas as compared to
      intratumoral lymphatics. The specificity of D2-40 as a lymphatic endothelial
      marker was also confirmed. The results of our study support the possibility of
      using the determination of tumor lymphangiogenesis to identify patients of HNSCC
      who are at risk of developing the lymph node metastasis.

PMID- 29456953
TI  - Histopathological Analysis of the Effects of Corticosteroids on Vocal Cords:
      Experimental Study.
AB  - Local treatment with corticosteroids results in side effects involving the upper
      respiratory tract including candidiasis, sore throat, and dysphonia. Although
      these effects are well known, they have not been evaluated using a
      histopathological approach. This study investigated the histopathological aspects
      of steroid-induced dysphonia. A total of 16 female Wistar albino rats were
      divided into two groups. The eight rats in the experimental group were given an
      inhaled dose of mometasone furoate daily for 4 weeks. The control group was kept
      at room temperature for 4 weeks. The vocal cords were evaluated
      histopathologically using hematoxylin and eosin staining. Both groups had typical
      epithelial lining and basal membranes. Inflammation differed between the two
      groups (P = 0.024). There were no differences in squamous metaplasia and
      hyperplasia (P = 0.302 and 0.302, respectively). This study revealed that inhaled
      corticosteroids inhibit mucosal immunity, and may result in reversible mucosal
      changes.

PMID- 29456954
TI  - Comparison of the Transient Evoked Otoacoustic Emissions (TEOAEs) and Distortion
      Products Otoacoustic Emissions (DPOAEs) in Normal Hearing Subjects With and
      Without Tinnitus.
AB  - The aim of this study was to investigate the possible role of cochlear outer hair
      cell function with TEOAE and DPOAE tests in patients with normal hearing and
      tinnitus. 25 tinnitus patients with normal hearing sensitivity selected as study
      group. Control group consist of 50 normal hearing subjects without tinnitus. All
      subjects had thresholds below 25 dBHL at frequencies 250-8,000 Hz, tympanogram
      type A and normal acoustic reflex thresholds. TEOAE were recorded with click
      stimulus at 80 dB SPL at 1,000, 2,000, 3,000 and 4000 Hz. DPOAE were measured at
      frequencies 1,000-8,000 Hz and intensity of L1 55 dB SPL and L2 65 dB SPL.
      Amplitude of DPOAE and TEOAE were decreased in all frequencies in study group.
      There was significant difference regarding prevalence abnormal TEOAE and DPOAE
      between study group and control group. There was relationship between dysfunction
      of outer hair cells and tinnitus in subjects with normal hearing.

PMID- 29456955
TI  - Increased Atherosclerosis Correlates with Subjective Tinnitus Severity.
AB  - The aim of the present study was to investigate whether increased intima media
      thickness was associated with the severity of subjective non-pulsatile tinnitus
      and hearing loss. Data of the patients who came to Otorhinolaryngology Department
      of Isparta Government Hospital with subjective non-pulsatile tinnitus complaint,
      between January 2012 and June 2013, were evaluated retrospectively. A total of
      215 patients were included in the present study. Hearing tests, biochemical
      analysis, tinnitus handicap inventory (THI), visual analogue scale (VAS) and
      doppler ultrasonography results of the patients were reviewed and recorded. The
      patients were classified into two groups as those having an increased intima
      media thickness and those having a normal intima media thickness. The said groups
      were compared with respect to age, gender, THI, VAS, hearing test findings and
      lipid values. Moreover, THI and VAS groups were compared with respect to intima
      media thickness. In the group having increased intima-media thickness, THI and
      VAS average, frequency of hypertension, total cholesterol, low density
      lipoprotein and triglyceride averages and mean frequencies obtained by hearing
      test were significantly higher. Comparison of THI and VAS groups showed that
      intima-media thickness was significantly different between those having a mild
      tinnitus and those having a severe tinnitus. Increased intima-media thickness was
      associated with the severity of subjective non-pulsatile tinnitus and hearing
      loss. For this reason, the carotid system should be examined in subjective non
      pulsatile tinnitus patients.

PMID- 29456956
TI  - Juvenile Nasopharyngeal Angiofibroma: Combined Approach for Excision,
      Transpalatal and Endoscopic; A New Perspective.
AB  - Juvenile angiofibroma is a rare, highly vascular, histologically benign but
      locally invasive tumour, affecting predominantly male adolescents. To describe
      our experience in diagnosis of angiofibroma and treatment by combined endoscopic
      and transpalatal route. We analysed a case series of 50 patients of
      nasopharyngeal angiofibroma in Fisch stages I and II who presented at our
      institute during a period of four years 2011-2014, their clinical presentation,
      their treatment by combined transpalatal and endoscopic approach, intraoperative
      and post operative course, complications and tumour recurrence. Patients were
      aged 8-26 years. All patients were treated surgically by combined approach
      endoscopic and transpalatal. The mean operation time was 90 min, and the mean
      bleeding volume was 300 ml. Only 8 % patients came with recurrence and only 10 %
      came with palatal perforation (fistula formation). With gratifying results we
      advocate this novel technique for the treatment of early to intermediate JNA.

PMID- 29456957
TI  - "Is Cone Beam Computed Tomography (CBCT) a Potential Imaging Tool in ENT
      Practice?: A Cross-Sectional Survey Among ENT Surgeons in the State of Odisha,
      India.
AB  - This questioner survey aimed about awareness of the Cone Beam Computed Tomography
      (CBCT) machine and its various clinical applications in ENT, among the ENT
      surgeons in the state of Odisha. 150 questioner forms on CBCT were distributed to
      the all the participating ENT surgeons at a state level ENT conference, out of
      which the response rate was 110. The participants were asked to answer 30
      multiple choice questions, which were divided into 3 parts; general information
      on CBCT, general approach to CBCT and practice related to CBCT. The statistical
      analysis of the data collected was carried out by a Chi square test to compare
      the means at a significance level of P < 0.05. The response rate for this study
      was 73%. The mean age of the participant ENT surgeons was 47.9 (+/-19.2). Of the
      study population, 71.2% (89) did not ever advice CBCT in their practice. Only
      33.9% (38) of the population believed that CBCT is more beneficial in the field
      of ENT. Only 25% (28) knew that CBCT requires lower radiation dose than
      conventional CT. 28.1% (31) of population believed that the spatial orientation
      is better in CBCT than CT. 62.5% (69) of the population did not knew that CBCT
      can be used in imaging sinusitis of dental origins. 75% (83) of the population
      did not knew that CBCT can be used in diagnosis of obstructive sleep apnoea and
      visualizing airway space. Only 18.8% (21) of the study population agreed that the
      CBCT has the potential to replace conventional CT in ENT imaging in future. In
      the conclusion, this study clearly showed that the number of ENT surgeons
      advising CBCT imaging in their practice is very less. The knowledge about various
      advantages and clinical applications of CBCT had been very limited. However,
      through continuing medical education and conducting various seminars and
      workshops on CBCT, imparting chapters on CBCT, in the undergraduate and post
      graduate curriculum will definitely help increase the awareness on CBCT among ENT
      fraternity.

PMID- 29456958
TI  - Etiology of Noise-Induced Hearing Loss (NIHL) and its Symptomatic Correlation
      with Audiometry Observations in Type II Diabetes.
AB  - Type II diabetic mellitus (DM) is a chronic metabolic disease that impairs normal
      insulin production and glucose transport to the liver and muscles. In the India,
      about 1-5% population suffer from diabetes or related complication. So there is
      need to cure this disease. DM chronic auditory complications may include spiral
      ganglia atrophy, degeneration of the vestibulocochlear nerve myelin sheath,
      reduction of the number of spiral lamina nerve fibres, and thickening of the
      capillary walls of the stria vascularis and small arteries. This study aims to
      know the incidence of common parameters, blood sugar levels, levels of lipids and
      the hearing thresholds of individuals. It is a Noise-Induced Hearing Loss
      research study featuring hearing impairment in transport workers diagnosed as
      type II diabetic. All individuals were interviewed by various questioners related
      to listening ability of subjects and underwent a physical examination, blood
      investigations and audiometry. Hearing impairment was more prevalent among adults
      with diabetes. Sensory neuron hearing loss is predominant in both study groups.
      Mixed Bilateral Hearing Loss showed significant p value in (>.001) by audiometry.
      The percentage of hearing loss in diabetes (ranges 5.3-28.1%) and in non
      diabetics (ranges 3.4-24.1%) and risk factors in diabetes (ranges 22.8-35.1%)
      over nondiabetics (ranges 17.2-20.1%) which is eye opener. The correlation
      between type II diabetes and hearing impairment was independent of known risk
      factors for hearing impairment, such as noise exposure, build-up wax, ototoxic
      medication, smoking, tobacco chewing etc.

PMID- 29456959
TI  - Bleomycin Sclerotherapy in Lymphangiomas of Head and Neck: Prospective Study of 8
      Cases.
AB  - The aim of this study is to evaluate the role of bleomycin as a primary mode of
      nonsurgical treatment in lymphangiomas of head and neck and study their
      complications. This is a prospective study of 8 patients diagnosed with
      lymphangioma of head and neck presenting to ENT department of Tata main Hospital
      from December 2014 to January 2017. They were clinically and radiologically
      evaluated and treated with intralesional injection of bleomycin diluted in normal
      saline. Complete resolution was seen in 62.5% (5/8) of patients, 25% (2/8) had
      good response while 12.5% (1/8) had a poor response. No major complications were
      noted apart from fever and inflammation. Intralesional bleomycin can be used as a
      primary modality of treatment.

PMID- 29456960
TI  - Evaluation and Customization of WHO Safety Checklist for Patient Safety in
      Otorhinolaryngology.
AB  - The WHO has designed a safe surgery checklist to enhance communication and
      awareness of patient safety during surgery and to minimise complications. WHO
      recommends that the check-list be evaluated and customised by end users as a tool
      to promote safe surgery. The aim of present study was to evaluate the impact of
      WHO safety checklist on patient safety awareness in otorhinolaryngology and to
      customise it for the speciality. A prospective structured questionnaire based
      study was done in ENT operating room for duration of 1 month each for cases,
      before and after implementation of safe surgery checklist. The feedback from
      respondents (surgeons, nurses and anaesthetists) was used to arrive at a
      customised checklist for otolaryngology as per WHO guidelines. The checklist
      significantly improved team member's awareness of patient's identity (from 17 to
      86%) and each other's identity and roles (from 46 to 94%) and improved team
      communication (from 73 to 92%) in operation theatre. There was a significant
      improvement in preoperative check of equipment and critical events were discussed
      more frequently. The checklist could be effectively customised to suit
      otolaryngology needs as per WHO guidelines. The modified checklist needs to be
      validated by otolaryngology associations. We conclude from our study that the WHO
      Surgical safety check-list has a favourable impact on patient safety awareness,
      team-work and communication of operating team and can be customised for
      otolaryngology setting.

PMID- 29456961
TI  - Rhinoorbitocerebral Mucormycosis with Maggots in a Neglected Diabetic Patient.
AB  - Mucormycosis is a rare opportunistic fungal infection in immunocompromised
      patients, Rhizopus species are most common, sometimes mucormycosis can be life
      threatening we report a case of rhinoorbitocerebral mucormycosis a patient with
      diabetic ketoacidosis secondarily infected by maggots with altered consciousness
      and metabolic decompensation.

PMID- 29456962
TI  - Neuroectodermally Derived Neoplasm of Tonsil: Difficulty in Histomorphological
      Diagnosis.
AB  - Esthesioneuroblastomas are rare neuroectodermally derived neoplasms occurring in
      the upper nasal septum or cribriform plate. They have been rarely reported in
      other sites, when they are called ectopic esthesioneuroblastomas. Due to the
      scarcity of reports, publications and molecular/genetic studies of these tumours,
      their diagnosis is likely to be missed when they are ectopic. Similar to the case
      report in this journal by Zahedi et al., we had a case of neuroectodermally
      derived neoplasm of the tonsil, which was difficult to diagnose, due to the site
      of occurrence being unknown for these tumours.

PMID- 29456963
TI  - Endoscopic Thyroid Surgery Through Trans-oral Vestibular Approach (TOVA): A Case
      Series and Review of Literature.
AB  - Endoscopic surgery is now standard of care for different Endocrine Disorders; the
      endoscopic thyroid surgery is becoming more popular and different approaches has
      been practice by many thyroid surgeon worldwide. Trans-orovestibular approach,
      based on the principle of natural orifice transluminal surgery is truly scar free
      thyroid surgery and has minimal dissection. We are presenting here three cases of
      benign solitary thyroid nodule operated endoscopically through trans-oro
      vestibular approach in one male and two female patients. Described about the
      approach, challenges during surgery and outcome. These surgeries documented very
      few in literatures in live human patients. Transoral endoscopic thyroid surgery
      through vestibular approach is shortest and direct remote access approach. The
      need of limited dissection in this approach provides less complication and
      excellent cosmetic outcome in strictly selected patients.

PMID- 29456964
TI  - Anatomical Correlation Between Nasal Vascularisation and the Design of the
      Endonasal Pedicle Flaps.
AB  - Arteries that supply the nasal septum and the lateral nasal wall include vessels
      that originate from the external carotid artery and from the internal carotid
      artery. A variety of local endonasal pedicle flaps can be used in different
      anatomical areas for endoscopic skull base reconstruction. The main flaps are
      based on terminal branches of the sphenopalatine artery and on anterior ethmoidal
      artery. This study will describe the anatomy of these vessels and their
      relationship with the main flaps.

PMID- 29456965
TI  - Corrigendum: Enhanced Cytotoxic Effects of Combined Valproic Acid and the Aurora
      Kinase Inhibitor VE465 on Gynecologic Cancer Cells.
AB  - [This corrects the article on p. 58 in vol. 3, PMID: 23519775.].

PMID- 29456967
TI  - Editorial: Parasite Infections: From Experimental Models to Natural Systems.

PMID- 29456966
TI  - Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand
      of Lipid Metabolism in Metastatic Cells.
AB  - Tumor cells are subjected to a broad range of selective pressures. As a result of
      the imposed stress, subpopulations of surviving cells exhibit individual
      biochemical phenotypes that reflect metabolic reprograming. The present work
      aimed at investigating metabolic parameters of cells displaying increasing
      degrees of metastatic potential. The metabolites present in cell extracts
      fraction of tongue fibroblasts and of cell lines derived from human tongue
      squamous cell carcinoma lineages displaying increasing metastatic potential (SCC9
      ZsG, LN1 and LN2) were analyzed by 1H NMR (nuclear magnetic resonance)
      spectroscopy. Living, intact cells were also examined by the non-invasive method
      of fluorescence lifetime imaging microscopy (FLIM) based on the auto fluorescence
      of endogenous NADH. The cell lines reproducibly exhibited distinct metabolic
      profiles confirmed by Partial Least-Square Discriminant Analysis (PLS-DA) of the
      spectra. Measurement of endogenous free and bound NAD(P)H relative concentrations
      in the intact cell lines showed that ZsG and LN1 cells displayed high
      heterogeneity in the energy metabolism, indicating that the cells would oscillate
      between glycolysis and oxidative metabolism depending on the microenvironment's
      composition. However, LN2 cells appeared to have more contributions to the
      oxidative status, displaying a lower NAD(P)H free/bound ratio. Functional
      experiments of energy metabolism, mitochondrial physiology, and proliferation
      assays revealed that all lineages exhibited similar energy features, although
      resorting to different bioenergetics strategies to face metabolic demands. These
      differentiated functions may also promote metastasis. We propose that lipid
      metabolism is related to the increased invasiveness as a result of the
      accumulation of malonate, methyl malonic acid, n-acetyl and unsaturated fatty
      acids (CH2)n in parallel with the metastatic potential progression, thus
      suggesting that the NAD(P)H reflected the lipid catabolic/anabolic pathways.

PMID- 29456968
TI  - Alternative Splicing of Differentiated Myeloid Cell Transcripts after Infection
      by Anaplasma phagocytophilum Impacts a Selective Group of Cellular Programs.
AB  - Eukaryotic proteome diversity exceeds that encoded within individual genes, and
      results in part from alternative splicing events of pre-messenger RNA. The
      diversity of these splicing events can shape the outcome in development and
      differentiation of normal tissues, and is important in pathogenic circumstances
      such as cancer and some heritable conditions. A role for alternative splicing of
      eukaryotic genes in response to viral and intracellular bacterial infections has
      only recently been recognized, and plays an important role in providing fitness
      for microbial survival, while potentially enhancing pathogenicity. Anaplasma
      phagocytophilum survives within mammalian neutrophils by reshaping
      transcriptional programs that govern cellular functions. We applied next
      generation RNAseq to ATRA-differentiated HL-60 cells established to possess
      transcriptional and functional responses similar to A. phagocytophilum-infected
      human neutrophils. This demonstrated an increase in transcripts with infection
      and high proportion of alternatively spliced transcript events (ASEs) for which
      predicted gene ontology processes were in part distinct from those identified by
      evaluation of single transcripts or gene-level analyses alone. The alternative
      isoforms are not on average shorter, and no alternative splicing in genes
      encoding spliceosome components is noted. Although not evident at gene-level
      analyses, individual spliceosome transcripts that impact nearly all spliceosome
      components were significantly upregulated. How the distinct GO processes
      predicted by ASEs are regulated by infection and whether they are relevant to
      fitness or pathogenicity of A. phagocytophilum should be addressed in more
      detailed studies.

PMID- 29456969
TI  - Mutation of Agr Is Associated with the Adaptation of Staphylococcus aureus to the
      Host during Chronic Osteomyelitis.
AB  - Selection pressures exerted on Staphylococcus aureus by host factors may lead to
      the emergence of mutants better adapted to the evolving conditions at the
      infection site. This study was aimed at identifying the changes that occur in S.
      aureus exposed to the host defense mechanisms during chronic osteomyelitis and
      evaluating whether these changes affect the virulence of the organism. Genome
      assessment of two S. aureus isolates collected 13 months apart (HU-85a and HU
      85c) from a host with chronic osteomyelitis was made by whole genome sequencing.
      Agr functionality was assessed by qRT-PCR. Isolates were tested in a rat model of
      osteomyelitis and the bacterial load (CFU/tibia) and the morphometric
      osteomyelitic index (OI) were determined. The ability of the isolates to trigger
      the release of proinflammatory cytokines was determined on macrophages in
      culture. Persistence of S. aureus within the host resulted in an agrC frameshift
      mutation that likely led to the observed phenotype. The capacity to cause bone
      tissue damage and trigger proinflammatory cytokines by macrophages of the agr
      deficient, unencapsulated derivative (HU-85c) was decreased when compared with
      those of the isogenic CP8-capsulated parental strain (HU-85a). By comparison, no
      significant differences were found in the bacterial load or the OI from rats
      challenged with isogenic Reynolds strains [CP5, CP8, and non-typeable (NT)],
      indicating that lack of CP expression alone was not likely responsible for the
      reduced capacity to cause tissue damage in HU-85c compared with HU-85a. The
      production of biofilm was significantly increased in the isogenic derivative HU
      85c. Lack of agr-dependent factors makes S. aureus less virulent during chronic
      osteomyelitis and alteration of the agr functionality seems to permit better
      adaptation of S. aureus to the chronically infected host.

PMID- 29456970
TI  - The Complement Binding and Inhibitory Protein CbiA of Borrelia miyamotoi Degrades
      Extracellular Matrix Components by Interacting with Plasmin(ogen).
AB  - The emerging relapsing fever spirochete Borrelia (B.) miyamotoi is transmitted by
      ixodid ticks and causes the so-called hard tick-borne relapsing fever or B.
      miyamotoi disease (BMD). More recently, we identified a surface-exposed molecule,
      CbiA exhibiting complement binding and inhibitory capacity and rendering
      spirochetes resistant to complement-mediated lysis. To gain deeper insight into
      the molecular principles of B. miyamotoi-host interaction, we examined CbiA as a
      plasmin(ogen) receptor that enables B. miyamotoi to interact with the serine
      protease plasmin(ogen). Recombinant CbiA was able to bind plasminogen in a dose
      dependent fashion. Moreover, lysine residues appear to play a crucial role in the
      protein-protein interaction as binding of plasminogen was inhibited by the lysine
      analog tranexamic acid as well as increasing ionic strength. Of relevance,
      plasminogen bound to CbiA can be converted by urokinase-type plasminogen
      activator (uPa) to active plasmin which cleaved both, the chromogenic substrate S
      2251 and its physiologic substrate fibrinogen. Concerning the involvement of
      specific amino acids in the interaction with plasminogen, lysine residues located
      at the C-terminus are frequently involved in the binding as reported for various
      other plasminogen-interacting proteins of Lyme disease spirochetes. Lysine
      residues located within the C-terminal domain were substituted with alanine to
      generate single, double, triple, and quadruple point mutants. However, binding of
      plasminogen to the mutated CbiA proteins was not affected, suggesting that lysine
      residues distant from the C-terminus might be involved in the interaction.

PMID- 29456971
TI  - Molecular, biochemical and kinetic analysis of a novel, thermostable lipase
      (LipSm) from Stenotrophomonas maltophilia Psi-1, the first member of a new
      bacterial lipase family (XVIII).
AB  - Background: Microbial lipases catalyze a broad spectrum of reactions and are
      enzymes of considerable biotechnological interest. The focus of this study was
      the isolation of new lipase genes, intending to discover novel lipases whose
      products bear interesting biochemical and structural features and may have a
      potential to act as valuable biocatalysts in industrial applications. Results: A
      novel lipase gene (lipSm), from a new environmental Stenotrophomonas maltophilia
      strain, Psi-1, originating from a sludge sample from Psittaleia (Greece), was
      cloned and sequenced. lipSm was further overexpressed in E. coli BL21(DE3) and
      the overproduced enzyme LipSm was purified and analyzed in respect to its
      biochemical and kinetic properties. In silico analysis of LipSm revealed that it
      is taxonomically related to several uncharacterized lipases from different
      genera, which constitute a unique clade, markedly different from all other
      previously described bacterial lipase families. All members of this clade
      displayed identical, conserved consensus sequence motifs, i.e. the catalytic
      triad (S, D, H), and an unusual, amongst bacterial lipases, Y-type oxyanion hole.
      3D-modeling revealed the presence of a lid domain structure, which allows LipSm
      to act on small ester substrates without interfacial activation. In addition, the
      high percentage of alanine residues along with the occurrence of the AXXXA motif
      nine times in LipSm suggest that it is a thermostable lipase, a feature verified
      experimentally, since LipSm was still active after heating at 70  degrees C for
      30 min. Conclusions: The phylogenetic analysis of LipSm suggests the
      establishment of a new bacterial lipase family (XVIII) with LipSm being its first
      characterized member. Furthermore, LipSm is alkaliphilic, thermostable and lacks
      the requirement for interfacial activation, when small substrates are used. These
      properties make LipSm a potential advantageous biocatalyst in industry and
      biotechnology.

PMID- 29456972
TI  - The Effect of Levothyroxine and Selenium versus Levothyroxine Alone on Reducing
      the Level of Anti-thyroid Peroxidase Antibody in Autoimmune Hypothyroid Patients.
AB  - Background: Due to the prevalence of autoimmune hypothyroidism and its effects on
      physical and mental health it is necessary to provide a treatment which is also
      effective in preventing the progression of sub-clinical hypothyroidism in these
      patients. This study aims to investigate the effect of selenium supplementation
      on of anti-thyroid hormone antibodies in these patients. Materials and Methods:
      In a randomized clinical trial, 70 patients with autoimmune hypothyroidism
      randomly divided into two groups of 35 each, the first group was treated with
      oral selenium treatment with levothyroxine (LT4) and to the second group along
      with LT4, placebo was also prescribed. Serum selenium level, thyroid hormones and
      anti-thyroid hormone antibodies before and after 3 months of treatment in both
      groups, were determined, and the results were analyzed using SPSS software.
      Results: The mean of the serum anti-thyroid peroxidase serum level in the
      intervention group before and after treatment was 682.18 +/- 87.25 and 522.96 +/-
      47.21 and the difference before and after treatment was statistically significant
      (P = 0.021). The level of this antibody before and after treatment in the control
      group was 441 +/- 53.54 and 501.18 +/- 77.68, and no significant differences
      between two groups were observed before and after treatment (P = 0.42).
      Conclusion: Selenium supplementation may help to reduce the levels of antibodies
      in patients with autoimmune hypothyroidism.

PMID- 29456973
TI  - Preventive Effects of Pre- and Intra-operative Marcaine, Lidocaine, and Marcaine
      Plus Lidocaine on Pain Relief in Lumbar Disc Herination Open Surgery.
AB  - Background: As marcaine is administered to a great extent due to minor
      complications and reasonable expenses and as discectomy is prevalently used in
      Iran, this study makes a comparison between effect of marcaine alone, lidocaine
      alone, and marcaine plus lidocaine on pain relief of patients undergoing lumbar
      disc open surgery. Materials and Methods: In a clinical trial study, 192 patients
      were selected and randomly divided into four groups. Patients in Groups 1-4
      received 0.5 ml marcaine during surgery, 5 ml lidocaine 2% before incision, 5 ml
      lidocaine 2% before incision plus 5 ml marcaine during surgey and normal saline,
      respectively. After patients gained knowledge of visual analog scale (VAS)
      criteria, their severity of pain was measured and was recorded in their profiles,
      along with demographic details and history of diseases. After surgery and their
      transfer to their rooms, their severity of pain was measured and recorded again
      by using VAS criteria. Finally, difference between the four groups was compared
      by SPSS software. Results: The mean (+/-standard deviation) of postoperative pain
      in marcaine + lidocaine, marcaine, lidocaine, and normal saline was 3.5 +/- 1.3,
      3.5 +/- 1.6, 36.1.9, and 4.2 +/- 1.8, respectively, and we did not observe any
      significant difference in severity of pain after surgery in these groups (P =
      0.15). The highest and lowest degree of satisfaction occurred in marcaine
      lidocaine group and control group, respectively, (40 patients [83.3%] vs. 25
      patients [52.1%]). Conclusion: Lidocaine-marcaine treatment reduces the need to
      opiates in cases of postoperative pain relief of discectomy and provides patients
      with great satisfaction.

PMID- 29456974
TI  - Evaluation of Outcomes of Open Reduction and Internal Fixation Surgery in
      Patients with Type C Distal Humeral Fractures.
AB  - Background: In this study, functional state of patients with Type C distal
      humerus fractures undergone surgical plating was evaluated 6 and 12 months after
      the surgery in order to record postsurgical factors such as pain level and
      job/performance satisfaction. Materials and Methods: In this cross-sectional
      study, 46 patients with humerus fractures were recruited and their ability to do
      daily tasks, presence of degenerative changes, stability of elbow joint, and
      range of motion was evaluated. For assessment of response to surgery, Mayo score
      was used. Results: Among 46 patients, 45 (97.8%) of them had joint stability.
      Evaluation of postsurgical complications showed that six subjects (13%) had no
      complications, but superficial infection was observed in 12 (26.1%) subjects.
      Neuromuscular disorders in ulnar nerve were present in 11 subjects (23.9%),
      recurrent articular bursitis of elbow joint in 6 subjects (13%), stiffness of
      elbow joint in 29 subjects (63%), nonunion of fracture in 3 subjects (6.5%), and
      myositis ossification in 4 (8.7%) subjects. Furthermore, 18 (39.1%) patients
      presented with more than one (2-4) complications. Conclusion: Open reduction and
      internal fixation surgery with dual plating is the method of choice for treatment
      of Type C distal humeral fractures. Evaluation of long-term outcomes of this
      surgery could be done via several different questionnaires as many studies
      suggest. This study demonstrated that the outcomes of this surgery in Isfahan,
      Iran, have been noticeably inferior compared to results of the studies in other
      parts of the world.

PMID- 29456976
TI  - Respiratory Viruses in Febrile Neutropenic Patients with Respiratory Symptoms.
AB  - Background: Respiratory infections are a frequent cause of fever in neutropenic
      patients, whereas respiratory viral infections are not frequently considered as a
      diagnosis, which causes high morbidity and mortality in these patients. Materials
      and Methods: This prospective study was performed on 36 patients with neutropenia
      who admitted to hospital were eligible for inclusion with fever (single
      temperature of >38.3 degrees C or a sustained temperature of >38 degrees C for
      more than 1 h), upper and lower respiratory symptoms. Sampling was performed from
      the throat of the patient by the sterile swab. All materials were analyzed by
      quantitative real-time multiplex polymerase chain reaction covering the following
      viruses; influenza, parainfluenza virus (PIV), rhinovirus (RV), human
      metapneumovirus, and respiratory syncytial virus (RSV). Results: RV was the most
      frequently detected virus and then RSV was the most. PIV was not present in any
      of the tested samples. Furthermore, no substantial differences in the
      distribution of specific viral species were observed based on age, sex,
      neutropenia duration, hematological disorder, and respiratory tract symptoms and
      signs (P > 0.05). Conclusion: Our prospective study supports the hypothesis that
      respiratory viruses play an important role in the development of neutropenic
      fever, and thus has the potential to individualize infection treatment and to
      reduce the extensive use of antibiotics in immunocompromised patients with
      neutropenia.

PMID- 29456975
TI  - Self-rated Health and Mortality due to Kidney Diseases: Racial Differences in the
      United States.
AB  - Background: Although the role of self-rated health (SRH) on all-cause mortality
      is known, we still do not know whether SRH predicts death due to specific causes
      (e.g., kidney disease). The current study aimed to compare Blacks and Whites on
      the association between SRH and mortality due to kidney diseases. A nationally
      representative sample of adults in the United States was used to provide
      generalizable results to the United States population. Materials and Methods: The
      Americans' Changing Lives study is a nationally representative cohort, conducted
      from 1986-2011. The study followed 3361 Blacks (n = 1156) and Whites (n = 2205)
      for up to 25 years. The outcome was time to death due to kidney diseases, derived
      from death certificates and the National Death Index. Cox proportional hazards
      models were used to test whether race and baseline SRH interact on mortality due
      to kidney diseases. Results: In the pooled sample, poor SRH (odds ratio [OR] =
      2.29, 95% confidence interval [CI] = 1.24-4.24) was associated with an increased
      risk of death due to kidney diseases over the follow-up period. Baseline SRH also
      showed a significant interaction with race on the outcome (OR = 0.49, 95% CI =
      0.25-0.96), suggesting a stronger effect of SRH on deaths due to kidney diseases
      for Whites compared to Blacks. In race-specific models, poor SRH at baseline
      increased risk of death due to kidney diseases among Whites (OR = 2.23, 95% CI =
      1.14-4.34) but not Blacks (OR = 1.14, 95% CI = 0.54-2.41). Conclusions: Blacks
      and Whites differ regarding the predictive role of baseline SRH on death due to
      kidney diseases over time. Factors such as SRH better predict risk of mortality
      for Whites than for Blacks.

PMID- 29456977
TI  - Epidemiologic and Demographic Features, Therapeutic Intervention and Prognosis of
      the Patients with Cerebral Aneurysm.
AB  - Background: Cerebral aneurysms are a kind of cardiovascular diseases which are
      accompanied with high morbidity and mortality due to rupturing and causing
      subarachnoid hemorrhages. The current study aimed to determine epidemiologic and
      demographic features and prognosis of patients with cerebral aneurysms. Materials
      and Methods: In this cross-sectional study, 465 patients with cerebral aneurysms
      hospitalized in Al-Zahra Hospital were studied. The required information
      including demographic, epidemiologic, and clinical features of the disease were
      extracted from their records. The obtained data were analyzed using SPSS software
      and the factors associated with the prognosis of the disease were determined.
      Results: Four hundred and sixty-five cases with cerebral aneurysm undergoing
      surgery were investigated. The mean age of the patients was 48 +/- 14 years
      whereas 216 cases (46.5%) were male and 249 (53.5%) were female. Two hundred and
      thirty-seven patients (51%) remitted completely while the disease caused moderate
      disability in 84 cases (18.1%), severe disability in 24 ones (5.2%) and
      vegetative state in 9 cases (1.9%) and mortality in 57 ones while it was unknown
      in 54 cases (11.6%). In terms of the age of patient, WFNS index, anatomical
      position of aneurysm, type of aneurysm lesion, the incidence season of the
      disease, type of postoperative complications, family history and operative
      approach, the disease outcome had a significant difference while gender,
      ethnicity, and risk factors had no significant effect on the disease outcome.
      Conclusions: According to the type of aneurysm, the incidence position of the
      aneurysm and other epidemiologic, demographic, and clinical features, providing
      the prevention and treatment strategies is necessary.

PMID- 29456978
TI  - A Case of Tyrosinemia Type III with Status Epilepticus and Mental Retardation.
AB  - Tyrosinemia type III is an autosomal recessive disorder caused by the deficiency
      of 4- hydroxyphenylpyruvate dioxygenase (4-HPPD). It is characterized by elevated
      levels of blood tyrosine and massive excretion of its derivatives into the urine.
      Clinical findings of tyrosinemia type III include neurological symptoms and
      mental retardation. Only a few patients presenting with this disease have been
      described, and the clinical phenotype remains variable and unclear. We present a
      case, who was admitted to the hospital at the age of 4 months for recurrent
      seizures. Two months later, she was admitted again with status epilepticus.
      Laboratory data showed increased level of tyrosine in the blood. She was treated
      with a diet low in tyrosine and phenylalanine and anamix formula that leading to
      catch-up growth and improvement of her symptoms. Plasma tyrosine level dropped to
      normal values. In any child who presents with the neurologic symptom, some rare
      diagnosis like tyrosinemia type III should be considered.

PMID- 29456979
TI  - Quercetin Prevents Body Weight Loss Due to the Using of Superparamagnetic Iron
      Oxide Nanoparticles in Rat.
AB  - Background: Superparamagnetic iron oxide nanoparticles (SPION) have been largely
      considered for numerous applications in biomedicine such as magnetic resonance
      imaging, hyperthermia, cell tracking, anticancer treatment, and targeted delivery
      of drugs or genes. However, they may have side effects such body weight loss.
      Quercetin (QT), a strong antioxidant and free radical scavenger and a natural
      flavonoid, has a wide range of biological and therapeutic effects. In this study,
      the effect of QT on prevention of weight loss due to the using of SPION has been
      investigated. Materials and Methods: SPION and QT-SPION were administered orally
      at 50 and 100 mg/kg for 7 days. Then, the body weight was measured at the
      beginning and the end of the study. Results: Rats fed with 50 and 100 mg/kg SPION
      showed a significant weight loss, whereas those that fed with 50 mg/kg QT-SPION
      did not. A weight loss was observed in rats treated with 100 mg/kg of QT-SPION.
      Conclusions: The results of this study showed that quercetin could prevent weight
      loss due to the SPION.

PMID- 29456980
TI  - Effect of Patellar Electrocautery Neurectomy on Postoperative Pain among Patients
      Referred for Total Knee Arthroplasty.
AB  - Background: Anterior knee pain is a major problem in total knee arthroplasty
      (TKA). It is accepted that anterior knee pain (AKP) often contributes to a
      patellofemoral etiology; however, its etiology or treatment is not understood
      completely. Disabling pain receptors by electrocautery could theoretically lead
      to anterior knee area denervation. The present study aimed to evaluate the pain
      post-patellar denervation (PD) with electrocautery in TKA. Materials and Methods:
      Clinical results for 92 patients who underwent TKA (58 women, 34 men; mean age
      67.5 years) were analyzed. In addition to removal of all osteophytes, PD by
      electrocautery was performed on patella of treatment group (n = 46) and
      debridement alone including removing of all osteophytes was performed on the
      control group (n = 46). Knee Society System (KSS) score, patella score (PS), and
      visual analog scale (VAS) were used to determine pre- and post-operative AKP.
      Results: The follow-up duration was 10 months. No revision or reoperations were
      performed. There were no patellar fractures. On all parameters (KSS score, PS,
      and VAS), there was a statistically significant pre- to post-operative difference
      in favor of the denervation group only 3 weeks after operation; however, there
      was no statistically difference postoperation on other follow-ups (3, 6, and 10
      months). Conclusions: PD with electrocautery could reduce AKP in TKA without
      patellar resurfacing only in a short-term period postoperation.

PMID- 29456982
TI  - Early Outcome of Patient with Ulcerative Colitis who Received High Dose of
      Steroid and Underwent Two Staged Total Proctocolectomy.
AB  - Background: Ulcerative colitis (UC) is an idiopathic inflammatory disorder.
      Currently, the final treatment is colectomy. The aim of this study was to
      investigate the outcomes of proctocolectomy in patients that used a high dose of
      prednisolone. Materials and Methods: Seventy-five patients presenting for
      surgical management of histopathologically proven UC. All patients were offered
      total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA). Patients
      were divided into two groups: low dose of steroids (Group A) and high dose of
      steroid (Group B) consumers. Data from these patients after 2 years were reviewed
      and analyzed. Results: From total patients, 34 of them were male and 34 ones were
      female and seven patients underwent laparatomy. Overall incontinence rate was
      8.8%; dysplasia was 22%, pouchitis was 18.9% while mortality was nil. The length
      of hospital stay was 6.76 days in Group A and 9.21 days in Group B (P = 0.399).
      Leakage was observed in nine of the patients after surgery (P = 0.589). Fecal
      incontinence between two groups was not statistically different (P = 0.063).
      Conclusions: Laparoscopic TPC-IPAA is feasible in patients needing surgical
      management of UC. Preoperative treatment with high-dose corticosteroids is
      associated with an increased risk of complications and reoperations.

PMID- 29456981
TI  - Prevalence of CTX-M and TEM beta-lactamases in Klebsiella pneumoniae Isolates
      from Patients with Urinary Tract Infection, Al-Zahra Hospital, Isfahan, Iran.
AB  - Background: Extended-spectrum beta-lactamase (ESBL)-producing is a significant
      resistant mechanism to beta-lactams in Enterobacteriaceae, especially in
      Klebsiella pneumoniae. The main objectives of this study were to genetically
      characterize urinary clinical isolates of K. pneumoniae through the investigating
      of blaTEM, blaCTX-M and using molecular typing by Enterobacterial repetitive
      intergenic consensus polymerase chain reaction (ERIC-PCR) method. We also
      determined the frequency of antibiotic resistance of K. pneumoniae strains to
      characterize the beta-lactamases included. Materials and Methods: A cross
      sectional study was carried out to evaluate 98 strains of K. pneumoniae isolated
      from urine culture of outpatients referred to Al-Zahra Hospital, Isfahan, Iran.
      Antibiotic susceptibility testing was performed using Kirby-Bauer's method.
      Screening of ESBLs was carried out using double-disk screening test. PCR
      technique was performed to detect TEM and CTX-M genes. The total DNA of each
      strain was tested by ERIC-PCR. Results: In 98 K. pneumoniae studied clinical
      isolates, 25.5% were ESBL producing and 44.9% multidrug-resistant (MDR). From 25
      ESBL isolates, 23 (92%) cases showed MDR phenotype. In ESBL producing isolates,
      23 (92%) were blaCTX-M and 19 (76%) blaTEM positive. The antimicrobial drug
      susceptibilities of ESBL isolates indicated high resistant rates for cefotaxime
      and ceftazidime. All 25 ESBL producing isolates were resistant to cefotaxime.
      Complex patterns of fingerprints isolates showed that 36% of the isolates were
      belonged to the cluster no 5. Conclusion: This study revealed high antimicrobial
      resistance rates among ESBL isolates which can lead to various health
      difficulties. Epidemiological data collection from patients is recommended to
      develop the strategies to manage antibiotic resistance.

PMID- 29456983
TI  - The Role of Mas Receptor on Renal Hemodynamic Responses to Angiotensin 1-7 in
      Both Irreversible and Reversible Unilateral Ureteral Obstruction Rats.
AB  - Background: Unilateral ureteral obstruction (UUO) alters the expression of renin
      angiotensin system (RAS) components and angiotensin 1-7 (Ang 1-7) as a main arm
      of RAS is affected by UUO. The role of Mas receptor antagonist (A779) was
      examined in renal hemodynamic responses to Ang 1-7 in 3-day UUO and UUO removal
      (RUUO) in rats. Materials and Methods: Forty-five male Wistar rats were randomly
      divided into three groups of sham operated, UUO, and RUUO, while each group was
      divided into two subgroups treated with vehicle or A779. Renal blood flow (RBF)
      and renal vascular resistance (RVR) responses to graded Ang 1-7 infusion were
      measured at controlled renal perfusion pressure. Results: Mean arterial pressure
      response to Ang 1-7 was increased in vehicle-treated subgroup significantly (P <
      0.05) when compared with A779-treated subgroup. However, such observation was not
      seen in UUO and RUUO rats. The graded Ang 1-7 infusion increased RBF and
      decreased RVR significantly in vehicle-treated rats (P < 0.005). Furthermore, a
      significant difference was found between vehicle and A779-treated subgroups in
      sham, UUO, and RUUO groups (P < 0.005). Conclusion: Ang 1-7 could alter the
      kidney hemodynamics responses in ureteral obstruction models.

PMID- 29456984
TI  - The Efficacy of Internet-based Cognitive Behavioral Therapy on the Anxiety
      Disorders among Adolescent Girls.
AB  - Background: The prevalence of anxiety disorders among children and adolescents
      are found to be approximately between 8-12 and 5-10, respectively, and the long
      lasting effects of such disorders can expose the sufferers to impairment and
      dysfunction in several areas of life the examples of which are poor educational
      performance, low self-esteem, and depression. The present study aims to evaluate
      the efficacy of internet-based, cognitive-behavioral therapy (ICBT) in treating
      the anxiety disorders among adolescent females. Materials and Methods: The sample
      included thirty girls aged between 10 and 18 years suffering from a variety of
      anxiety disorders, under pharmaceutical therapy and referred to clinics of child
      and adolescent psychiatry specialists in Isfahan. The sample was selected through
      diagnostic interviews by psychiatrists based on the Diagnostic and Statistical
      Manual of Mental Disorders, 4th Edition, Text Revision; afterward, they were
      randomly assigned to either the experimental or the control groups. To evaluate
      the efficacy of an ICBT in reducing anxiety disorder symptoms, Screen for Child
      Anxiety Related Emotional Disorders questionnaire was administered among the
      patients both before and 4 weeks after the treatment. Results: The covariance
      analysis results aimed to compare the anxiety disorder score variations between
      the two groups which demonstrate the fact that anxiety disorder scores in these
      two groups differ from one another (P < 0.001). Conclusions: This study is
      comprised of two Conclusions.the significant reduction in the mean of anxiety
      disorders scores in the experimental group compared to those in control group can
      be indicative of the efficacy of ICBT. In addition the significant reduction in
      the average of anxiety disorders symptoms' scores according to the type of
      anxiety disorders in the experimental group, compared to those in control group,
      can be indicative of the efficacy of ICBT.

PMID- 29456985
TI  - Evaluation of miR-21 Inhibition and its Impact on Cancer Susceptibility Candidate
      2 Long Noncoding RNA in Colorectal Cancer Cell Line.
AB  - Background: Both microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have been
      shown to have a critical role in the regulation of cellular processes such as
      cell growth and apoptosis, as well as cancer progression and metastasis. lncRNAs
      are aberrantly expressed in many diseases including cancer. Although it is well
      known that miRNAs can target a large number of protein-coding genes, little is
      known whether miRNAs can also target lncRNAs. In the present study, we determine
      whether miR-21 can regulate lncRNA cancer susceptibility candidate 2 (CASC2) in
      colorectal cancer. Materials and Methods: LS174T cells were transfected with
      locked nucleic acid (LNA)-anti-miR-21 and scrambled LNA for 24, 48 and 72 h. The
      expression of miR-21 and lncCASC2 was evaluated by quantitative reverse
      transcriptase polymerase chain reaction. Results: However, contrary to what we
      expected and reported by others, lncCASC2 quantity was significantly reduced in
      LNA treated LS174T cells compared to the scrambled treated and normal untreated
      cells (P < 0.05). Conclusion: The interaction of miRNA and lncRNA are not as
      simple as suggested by other reports. Moreover, it could be complex molecular
      mechanisms underlying the communication of various noncoding RNA elements.

PMID- 29456986
TI  - Extract from Teucrium polium L. Protects Rat Heart against Oxidative Stress
      Induced by Ischemic-reperfusion Injury.
AB  - Background: The deleterious effect of oxidative stress on myocardial ischemia
      reperfusion (I/R) has already been shown in previous studies. Since Teucrium
      polium has anti-oxidative and cardio-protective properties, the aim of this study
      was to investigate the effects of this plant on I/R injuries in the isolated rat
      heart. Materials and Methods: The myocardial I/R injury of rat was created by
      Langendorff retrograde perfusion technology. The heart was preperfused with Krebs
      Henseleit (K-H) solution containing T. polium extract for 20 min before 20 min
      global ischemia, and then the reperfusion with K-H bicarbonate buffer was
      conducted for 40 min. The left ventricular developed pressure and the maximum
      up/down rate of the left ventricular pressure (+/-dp/dtmax) were recorded by
      physiological recorder as the myocardial function. Lactate dehydrogenase (LDH)
      and creatine kinase (CK) activities in the effluent were measured to determine
      the myocardial injury degree. Thiobarbituric acid reactive substances (TBARS),
      total thiol groups (-SH), superoxide anion dismutase (SOD), and catalase (CAT) in
      myocardial tissue were detected to determine the oxidative stress degree.
      Results: The results showed that the pretreatment with T. polium significantly
      enhanced cardiac parameters and the coronary artery flow, decreased the LDH, CK
      activities, and TBARS level, whereas it increased - SH groups, SOD and CAT
      activities. Conclusions: Our findings indicated that T. polium could provide
      protection for heart against the I/R injury which may be related to the
      improvement of myocardial oxidative stress states.

PMID- 29456987
TI  - Effects of Streptokinase and Normal Saline on the Incidence of Intra-abdominal
      Adhesion 1 Week and 1 Month after Laparotomy in Rats.
AB  - Background: Intra-abdominal adhesions after surgery are usually in the form of
      bands and can annoy the patient throughout life causing repeated surgical
      procedures. Therefore, any action to prevent adhesions after surgery can increase
      longevity and quality of life. For this aim, this study investigates the effect
      of streptokinase and normal saline on the 7th day and 1 month after laparotomy.
      Materials and Methods: Experimental study was conducted on thirty healthy male
      Wistar rats weighing 200-250 g with age of 3 months divided into three groups of
      10. Group I: No treatment, Group II: Received normal saline, and Group III:
      Received normal saline and streptokinase at the same time. One week and 1 month
      after laparotomy, the frequency of the presence or absence of adhesion bands was
      performed by a person who was unaware of the sample grouping. The collected
      information was analyzed with the SPSS software (version 16; SPSS Inc., Chicago,
      IL, USA). Results: Adhesion frequency was found to be 20% on the 7th day (early)
      and 1 month after laparotomy (late) for Group 1, and it was 40% on early and late
      for Group II, while 0% on the early and late for Group III. Hence, in the group
      receiving streptokinase, no early or late adhesion was observed; therefore, it
      had a significant role in the prevention of intra-abdominal adhesions (P < 0.05).
      However, adhesions in the group receiving normal saline had no remarkable
      difference with the group receiving no drug (P > 0.05). Conclusion: According to
      the results of our study, we believe that streptokinase could be a good
      antiadhesive agent considering its effectiveness.

PMID- 29456988
TI  - Effect of Twine-arginine Translocation-signaling Fusion System and Chaperones Co
      expression on Secretory Expression of Somatropin.
AB  - Background: Twine-arginine translocation (TAT) system is one of the exporting
      systems in Escherichia coli which could transport fully/semi-correctly folded
      proteins outside the reductive cytoplasmic space. In combination with co
      expression with a chaperone system, the correctly folded proteins could be
      transported to oxidative periplasmic space and culture media to pass the main
      limitations in E. coli expression system such as misfolding and inclusion body
      formation. Materials and Methods: To study the effectiveness of signaling
      sequences and chaperone co-expression on the translocation of expressed protein,
      somatropin was selected as the target. Two common signal sequences in TAT system
      (TorA and SufI) were added at the N-terminal of somatropin and the cassettes were
      co-expressed in E. coli BL21 (DE3) by a chaperone team including DnaK/J-GrpeE.
      Results: The expression pattern studies including Western blotting and sodium
      dodecyl sulfate polyacrylamide gel electrophoresis confirmed that somatropin is
      expressed in two cassettes. However, the pattern was different for two signaling
      sequences. Conclusion: The results confirmed that the approach of using TAT
      signaling sequences and co-expression with the chaperone team could enhance
      translocation of protein to periplasmic space and culture media compared to
      control groups. Western blotting results showed that the signal sequence TorA
      could transport more expressed proteins to the periplasmic space and culture
      media in comparison with SufI. However, there was a considerable amount of human
      growth hormone in the cytoplasm which could not be transported outside the
      cytoplasmic space.

PMID- 29456989
TI  - Effect of Thymoquinone on Reproductive Parameter in Morphine-treated Male Mice.
AB  - Background: Thymoquinone as the main active component of Nigella sativa might
      have a various pharmacological effects such as antiapoptotic and antioxidant.
      Morphine is commonly used for the treatment of severe pain that can increase the
      generation of free radicals and affects the spermatogenesis. This study was
      designed to evaluate protective effects of thymoquinone against morphine-induced
      damages, sperm viability, count, motility, morphology and testis histology, and
      nitric oxide and testosterone hormone of the mice. Materials and Methods: In this
      experimental study, we divided 48 mice into eight groups (n = 6); various doses
      of thymoquinone (2, 10, and 20 mg/kg) and morphine (20 mg/kg) plus thymoquinone
      (2, 10, and 20 mg/kg) were administered intraperitoneally to 48 male mice for 30
      consequent days. Male reproductive parameters including testis weight,
      testosterone hormone, serum nitric oxide, germinal thickness, sperm morphology,
      count, viability, and motility were analyzed and compared. Results: The results
      indicated that morphine administration significantly decreased germinal
      thickness, testis weight, testosterone level, viability, morphology, count, and
      motility of sperm and increased nitric oxide as compared to saline group (P <
      0.05). However, increasing the dose of thymoquinone in the thymoquinone and
      thymoquinone plus morphine groups significantly decreases nitric oxide level (P <
      0.05) while significantly boosted motility, morphology, count, viability of sperm
      cells, germinal thickness, and testosterone hormone in all groups as compared to
      morphine group (P < 0.05). Conclusion: It seems that thymoquinone administration
      could increase the quality some of spermatozoa and improves morphine-induced
      adverse effects on reproductive parameters in male mice.

PMID- 29456990
TI  - Ketamine versus Ketamine / magnesium Sulfate for Procedural Sedation and
      Analgesia in the Emergency Department: A Randomized Clinical Trial.
AB  - Background: The present study was designed to evaluate the effectiveness of
      magnesium sulfate (MgSO4) in procedural sedation and analgesia (PSA) when
      combined with ketamine in patients with fractures in emergency departments and
      required short and painful emergency procedures. Materials and Methods: In this
      study, 100 patients with fractures and dislocations who were presented to the
      emergency departments and required PSA for short and painful emergency procedures
      were randomly allocated to groups of ketamine plus MgSO4 or ketamine alone. Train
      of four (TOF) stimulation pattern was assessed using nerve stimulator machine and
      compared between groups. Results: The mean age of studied patients was 46.9 +/-
      9.3 years old. 48% were male and 52% were female. No significant differences were
      noted between groups in demographic variables. The status of TOF, 2 min after the
      injection of ketamine (1.5 mg/kg), in both groups was similar. After the
      injection of the second dose of ketamine (1 mg/kg) the status of TOF in four
      patients in ketamine plus MgSO4 (0.45 mg/kg) group changed, it was three quarters
      but in ketamine group, the status of TOF in all patients was four quarters. The
      difference between groups was not statistically significant (P = 0.12).
      Conclusion: The findings revealed that for muscle relaxation during medical
      procedures in the emergency department, ketamine in combination with MgSO4 with
      this dose was not effective for muscle relaxation during procedures.

PMID- 29456991
TI  - Estimation and Projection of Prevalence of Colorectal Cancer in Iran, 2015-2020.
AB  - Background: Population aging and more prevalent westernized lifestyle would be
      expected to result in a markedly rising burden of colorectal cancer (CRC) in the
      future years. The aim of this study is to estimate the limited-time prevalence of
      CRC in Iran between 2015 and 2020. Materials and Methods: Aggregated CRC
      incidence data were extracted from the Iranian national cancer registry (IR.NCR)
      reports for 2003-2009 and from GLOBOCAN-2012 database for 2012. Incidence trends
      were analyzed by age groups, genders, histopathologic, and topographic subtypes
      to estimate annual percentage changes. Incidence was projected for 2020. The
      prevalence was estimated applying an adopted version of a previously introduced
      equation to estimate limited-time prevalence based on the incidence and survival
      data. Monte Carlo sensitivity analyses were applied to estimate 95% uncertainty
      levels (ULs). In each scenario, incidence, survival, annual percentage changes,
      and completeness of case ascertainment at IR.NCR were replaced under pre-assumed
      distributions. Results: Number of estimated within 1, 2-3 and 4-5-year CRC
      patients in 2015 were 13676 (95% UL: 10051-18807), 20964 (15835-28268), and 14485
      (11188-19293), respectively. Estimated 5-year prevalence for 2020 (99463; 75150
      134744) was 2.03 times of that for 2015. Highest 5-year prevalence was estimated
      in ages 55-59 for females and 75 + for males. Adenocarcinoma (41376; 31227 55898)
      was the most prevalent histologic subtype. The most prevalent tumor location was
      colon (30822, 23262-41638). Conclusion: A substantial growth in the prevalence of
      CRC survivors is highly expected for future years in Iran. Establishment of
      specialized institutes is highly recommended to provide medical and especially
      social supports for Iranian CRC survivors.

PMID- 29456992
TI  - National Immunization Campaigns with Oral Polio Vaccine Reduce All-Cause
      Mortality: A Natural Experiment within Seven Randomized Trials.
AB  - Background: A recent WHO review concluded that live BCG and measles vaccine (MV)
      may have beneficial non-specific effects (NSEs) reducing mortality from non
      targeted diseases. NSEs of oral polio vaccine (OPV) were not examined. If OPV
      vaccination campaigns reduce the mortality rate, it would suggest beneficial
      NSEs. Setting: Between 2002 and 2014, Guinea-Bissau had 15 general OPV campaigns
      and other campaigns with OPV plus vitamin A supplementation (VAS), VAS-only, MV,
      and H1N1 vaccine. In this period, we conducted seven randomized controlled trials
      (RCTs) with mortality as main outcome. Methods: Within these RCTs, we assessed
      whether the mortality rate was lower after-campaign than before-campaign. We used
      Cox models with age as underlying time and further adjusted for low birth-weight,
      season and time trend in mortality. We calculated the adjusted mortality rate
      ratio (MRR) for after-campaign vs before-campaign. Results: The mortality rate
      was lower after OPV-only campaigns than before, the MRR being 0.81 (95% CI = 0.68
      0.95). With each additional dose of campaign-OPV the mortality rate declined
      further (MRR = 0.87 (95% CI: 0.79-0.96) per dose) (test for trend, p = 0.005). No
      other type of campaign had similar beneficial effects. Depending on initial age
      and with follow-up to 3 years of age, the number needed to treat with campaign
      OPV-only to save one life was between 68 and 230 children. Conclusion: Bissau had
      no case of polio infection so the results suggest that campaign-OPV has
      beneficial NSEs. Discontinuation of OPV-campaigns in low-income countries may
      affect general child mortality levels negatively.

PMID- 29456993
TI  - Measuring Adolescent Self-Awareness and Accuracy Using a Performance-Based
      Assessment and Parental Report.
AB  - Aim: The aim of this study was to assess awareness of performance and performance
      accuracy for a task that requires executive functions (EF), among healthy
      adolescents and to compare their performance to their parent's ratings. Method:
      Participants: 109 healthy adolescents (mean age 15.2 +/- 1.86 years) completed
      the Weekly Calendar Planning Activity (WCPA). The discrepancy between self
      estimated and actual performance was used to measure the level of awareness. The
      participants were divided into high and low accuracy groups according to the WCPA
      accuracy median score. The participants were also divided into high and low
      awareness groups. A comparison was conducted between groups using WCPA
      performance and parent ratings on the Behavior Rating Inventory of Executive
      Function (BRIEF). Results: Higher awareness was associated with better EF
      performance. Participants with high accuracy scores were more likely to show high
      awareness of performance as compared to participants with low accuracy scores.
      The high accuracy group had better parental ratings of EF, higher efficiency,
      followed more rules, and were more aware of their WCPA performance. Conclusion:
      Our results highlight the important contribution that self-awareness of
      performance may have on the individual's function. Assessing the level of
      awareness and providing metacognitive training techniques for those adolescents
      who are less aware, could support their performance.

PMID- 29456994
TI  - Benign Cutaneous Peripheral Nerve Sheath Tumor with Hybrid Features: Report of
      Two Cases with Schwannoma/Perineurioma and Schwannoma/Neurofibroma Components.
AB  - Hybrid benign peripheral nerve sheath tumors are rare tumors exhibiting areas of
      more than one neural neoplasm such as schwannoma/neurofibroma,
      neurofibroma/perineurioma, or schwannoma/perineurioma. These tumors usually arise
      in the skin of the extremities and trunk, and less commonly affect extracutaneous
      sites. Here we report two cases of these tumors exhibiting hybrid features of
      schwannoma/perineurioma and schwannoma/neurofibroma located in the scalp and the
      ankle, respectively.

PMID- 29456995
TI  - A 25-Year-Old Male with Orogenital Ulcers, Rash, and Difficulty Swallowing.
AB  - A 25-year-old otherwise healthy male presented with new-onset odynophagia, rash,
      and orogenital ulcers. Despite treatment with antibiotics for presumed bacterial
      pharyngitis, the patient remained symptomatic, with abnormal vital signs and
      laboratory values. Upon dermatology consultation and histopathologic correlation,
      he was diagnosed with Behcet disease. Behcet disease is a rare rheumatologic
      condition that presents with recurrent oral ulcers and varying degrees of
      ophthalmic, neurologic, cardiac, and vascular disease. Given its protean nature,
      the treatment of Behcet disease is tailored to the patient's presentation and
      severity of organ involvement. Following treatment with colchicine and
      prednisone, the patient's symptoms improved rapidly.

PMID- 29456996
TI  - A 65-Year-Old Male with Primary Central Nervous System Diffuse Large B-Cell
      Lymphoma on Nivolumab with Oral Mucositis and Targetoid Plaques.
AB  - Background/Aims: The development of programmed cell death-1 (PD-1) inhibitors has
      greatly improved patient outcomes in the treatment of a variety of advanced
      malignancies. These novel immunotherapies are not without adverse effects, the
      most common of which are dermatologic. Methods: We report our experience with an
      atypical erythema multiforme-like eruption in a patient with primary central
      nervous system diffuse large B-cell lymphoma treated with nivolumab. Results: The
      patient presented with oral mucositis and scattered erythematous papules which
      progressed to targetoid purpuric plaques with hyperkeratotic centers.
      Histopathology demonstrated interface dermatitis with dyskeratotic keratinocytes
      and pigment incontinence. The patient experienced improvement of the eruption
      with discontinuation of nivolumab and on systemic and topical glucocorticoids.
      Conclusion: As PD-1 inhibitors become more widely used in the treatment of
      advanced malignancies, the early recognition and treatment of rare dermatologic
      toxicities remain of great importance.

PMID- 29456997
TI  - A 71-Year-Old Female with Myocardial Infarction and Long-Standing Ulcers on the
      Thigh.
AB  - Calciphylaxis is most commonly encountered in patients with end-stage renal
      disease; however, it is increasingly observed in nonuremic patients as well. It
      is important to consider and diagnose nonuremic calciphylaxis early, as prompt
      treatment and mitigation of associated risk factors is essential to improve long
      term outcomes for these patients. Here, we present the case of a 71-year-old
      woman with atrial fibrillation on warfarin, but without renal disease, who
      presented with two long-standing ulcers on her thigh and was diagnosed with the
      aid of biopsy with calciphylaxis. We review the existing literature on the
      subject and offer this case as a representative report of a clinicopathologic
      correlation for this disorder.

PMID- 29456998
TI  - A 12-Month-Old Healthy Girl with a New Oral Ulcer and Chronic Diaper Rash.
AB  - A 12-month-old healthy girl presented with a chronic diaper rash. Physical
      examination demonstrated crusting of the scalp, erythematous papules with
      surrounding petechiae on the lower abdomen, and an intraoral palatal ulcer.
      Further imaging demonstrated bone involvement. Histopathologic examination of
      involved skin and the intraoral ulcer demonstrated epithelioid histiocytes with
      "coffee bean-shaped" nuclei, staining positive for CD1a and langerin by
      immunohistochemistry, consistent with Langerhans cell histiocytosis (LCH). LCH is
      a disease entity of unknown etiology characterized by histiocytic proliferation
      that most commonly presents in young children. The cutaneous findings of LCH
      include a seborrheic dermatitis-like and/or red-brown papular eruption. Intraoral
      examination is crucial as oral mucosal and maxillofacial skeletal disease can
      also be seen in LCH. When a child presents with a recalcitrant seborrheic
      dermatitis-like eruption or chronic diaper rash, the clinician should be alerted
      to the possibility of LCH. Timely recognition and diagnosis of LCH is important
      for oncologic referral, evaluation, and treatment.

PMID- 29456999
TI  - A 53-Year-Old Male with Relapsed Diffuse Large B-Cell Lymphoma on Chemotherapy
      with a New Leg Lesion.
AB  - Patients with underlying malignancy who develop new skin findings while acutely
      ill often require skin biopsy for histologic evaluation and/or culture to reach a
      diagnosis. Here, we present the case of a 53-year-old male with relapsed diffuse
      large B-cell lymphoma on chemotherapy who developed new skin lesions on the leg.
      On exam, there were 2 nickel-sized, erythematous to violaceous round plaques with
      central necrotic cores on the right lower leg with relatively nonspecific
      clinical features for which the initial differential diagnosis was broad.
      Consensus on a diagnosis was reached upon histologic evaluation of his skin
      biopsy in the context of his clinical setting. This diagnosis led to a change in
      treatment plan, with subsequent clinical improvement.

PMID- 29457000
TI  - Dysplastic Nevus: A Fake Lesion?

PMID- 29457001
TI  - Control of Infectious Diseases in the Era of European Clinical Microbiology
      Laboratory Consolidation: New Challenges and Opportunities for the Patient and
      for Public Health Surveillance.
AB  - Many new innovative diagnostic approaches have been made available during the
      last 10 years with major impact on patient care and public health surveillance.
      In parallel, to enhance the cost-effectiveness of the clinical microbiology
      laboratories (CMLs), European laboratory professionals have streamlined their
      organization leading to amalgamation of activities and restructuring of their
      professional relationships with clinicians and public health specialists. Through
      this consolidation process, an operational model has emerged that combines large
      centralized clinical laboratories performing most tests on one high-throughput
      analytical platform connected to several distal laboratories dealing locally with
      urgent analyses at near point of care. The centralization of diagnostic services
      over a large geographical region has given rise to the concept of regional-scale
      "microbiology laboratories network." Although the volume-driven cost savings
      associated with such laboratory networks seem self-evident, the consequence(s)
      for the quality of patient care and infectious disease surveillance and control
      remain less obvious. In this article, we describe the range of opportunities that
      the changing landscape of CMLs in Europe can contribute toward improving the
      quality of patient care but also the early detection and enhanced surveillance of
      public health threats caused by infectious diseases. The success of this
      transformation of health services is reliant on the appropriate preparation in
      terms of staff, skills, and processes that would be inclusive of stakeholders. In
      addition, rigorous metrics are needed to set out more concrete laboratory service
      performance objectives and assess the expected benefits to society in terms of
      saving lives and preventing diseases.

PMID- 29457002
TI  - Early Dietary Patterns and Microbiota Development: Still a Way to Go from
      Descriptive Interactions to Health-Relevant Solutions.
AB  - Early nutrition and growth in the initial years of life are important
      determinants of later body weight and metabolic health in humans, and the current
      epidemic of obesity involving children requires a better understanding of causal
      and protective mechanisms and components in infant foods. This review focuses on
      recent evidence implicating feeding modes (e.g., breast milk and formula milk)
      and dietary transitions toward complementary foods in the progression of
      microbiota maturation in children. The literature exploring body weight outcomes
      of microbiota changes induced by diet in early life is limited. Representative
      studies addressing the use of probiotics in pregnant women and infants are also
      examined. Methodological and geo-cultural variations make it difficult to avoid
      (apparently) controversial findings. Most studies indicate differences in the
      microbiota of formula versus breastfed infants, but some do not. Duration of
      breastfeeding delays the maturation of the microbiota toward an adult-like
      profile. However, the effect size of the early feeding pattern on microbial
      function was found to be very small, and absent after the third year of life.
      There are several interesting mediators whereby milk composition can affect
      infants' microbiota and their optimization is a desirable strategy for
      prevention. But prevention of what? Although there are few correlative
      evaluations relating microbiota and body weight in early life, studies
      demonstrating a cause-effect relationship between diet-induced changes in early
      microbiota development and subsequent metabolic health outcomes in humans are
      still missing.

PMID- 29457003
TI  - A Physician's Perspective on Volunteering Overseas... It Is Not All about Sharing
      the Latest Technology.
AB  - As health-care professionals, there often comes a time in our career when we are
      intrigued by the possibility of participating in humanitarian work in underserved
      countries. However, the desire to serve is often tempered by some ambivalence
      about whether our skill sets are applicable in less technologically advanced
      health-care settings. Furthermore, there may be some concern about the cultural
      and logistical challenges one might face while working overseas. A volunteer may
      also be worried that, despite their best intentions, the medical personnel in the
      host country will not take advantage of our knowledge and their patients will not
      achieve the best results. As a consequence, a talented and well-intentioned
      professional may decide not to volunteer, resulting in a lost opportunity to
      participate in what can be an extremely rewarding experience. I will be
      discussing a number of key factors that can strongly influence the quality of
      one's experience from the perspective of a Hand Specialist. My comments will
      primarily be a reflection of my personal experience over 20 years as a member of
      Health Volunteers Overseas (www.hvousa.org).

PMID- 29457004
TI  - The Molecular Bases of the Dual Regulation of Bacterial Iron Sulfur Cluster
      Biogenesis by CyaY and IscX.
AB  - IscX (or YfhJ) is a protein of unknown function which takes part in the iron
      sulfur cluster assembly machinery, a highly specialized and essential metabolic
      pathway. IscX binds to iron with low affinity and interacts with IscS, the
      desulfurase central to cluster assembly. Previous studies have suggested a
      competition between IscX and CyaY, the bacterial ortholog of frataxin, for the
      same binding surface of IscS. This competition could suggest a link between the
      two proteins with a functional significance. Using a hybrid approach based on
      nuclear magnetic resonance, small angle scattering and biochemical methods, we
      show here that IscX is a modulator of the inhibitory properties of CyaY: by
      competing for the same site on IscS, the presence of IscX rescues the rates of
      enzymatic cluster formation which are inhibited by CyaY. The effect is stronger
      at low iron concentrations, whereas it becomes negligible at high iron
      concentrations. These results strongly suggest the mechanism of the dual
      regulation of iron sulfur cluster assembly under the control of iron as the
      effector.

PMID- 29457006
TI  - Progressive Depigmentation in a Patient with Panuveitis and Meningitis.

PMID- 29457005
TI  - Effectiveness of Platelet-Rich Plasma for Androgenetic Alopecia: A Review of the
      Literature.
AB  - Androgenetic alopecia (AGA) is a hair loss disorder affecting 80% of men and 50%
      of women throughout their lifetime. Therapies for AGA are limited and there is no
      cure. There is a high demand for hair restoration. Platelet-rich plasma (PRP), a
      treatment modality shown to promote wound healing, has also been explored as a
      treatment for AGA. This literature review was conducted to assess the
      effectiveness of PRP treatment for AGA. Twelve studies conducted from 2011 to
      2017 were evaluated and summarized by study characteristics, mode of preparation,
      and treatment protocols. A total of 295 subjects were given PRP or control
      treatment in these studies, and evaluated for terminal hair density, hair
      quality, anagen/telogen hair ratio, keratinocyte proliferation, blood vessel
      density, etc. Some studies also provided subject self-assessment reports. Most of
      the studies reviewed showed effectiveness of PRP in increasing terminal hair
      density/diameter. Additional investigations are needed to determine the optimal
      treatment regimen for high efficacy of PRP in AGA.

PMID- 29457007
TI  - The Dermoscopic "Pluck Out Sign" for Beard Trichotillomania.
AB  - Beard trichotillomania (TTM) is a rather uncommon entity. Hair is not easily
      plucked from the beard area, as patients need forceps or tweezers to perform
      their task. The diagnosis of beard TTM can be quite tricky as the location is not
      the most frequent one. Dermoscopy might in these cases be helpful to achieve the
      correct diagnosis. In this article, we describe for the first time the "pluck out
      sign" for beard TTM.

PMID- 29457008
TI  - A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and
      Classification.
AB  - Platelet-rich plasma (PRP) is currently used in different medical fields. The
      interest in the application of PRP in dermatology has recently increased. It is
      being used in several different applications as in tissue regeneration, wound
      healing, scar revision, skin rejuvenating effects, and alopecia. PRP is a
      biological product defined as a portion of the plasma fraction of autologous
      blood with a platelet concentration above the baseline. It is obtained from the
      blood of patients collected before centrifugation. The knowledge of the biology,
      mechanism of action, and classification of the PRP should help clinicians better
      understand this new therapy and to easily sort and interpret the data available
      in the literature regarding PRP. In this review, we try to provide useful
      information for a better understanding of what should and should not be treated
      with PRP.

PMID- 29457009
TI  - Acneiform Rash Caused by an Unlikely Drug: Topiramate.
AB  - Topiramate is an antiepileptic drug that can also be used for migraine
      prophylaxis, weight control, and even for methamphetamine dependence; the dosage
      margin is wide, and the list of side effects is shorter than with other
      anticonvulsants. We present the case of a 35-year-old man with a disseminated
      rash of the trunk and extremities after treatment with 25 mg of topiramate daily
      as a prophylactic migraine treatment. This case report is useful, as this patient
      was not polymedicated and had a score of 7 on the Naranjo Adverse Drug Reaction
      Probability Scale. The patient was diagnosed as atypical DRESS syndrome and
      resolved satisfactorily with symptomatic treatment and topiramate withdrawal;
      slowly, the lesions regressed. He required no further drugs for the dermatologic
      condition.

PMID- 29457010
TI  - Telogen Effluvium: Is There a Need for a New Classification? A Reply.

PMID- 29457011
TI  - Trichoscopic Features of Linear Morphea on the Scalp.
AB  - Linear scleroderma en coup de sabre (LSCS) is the most common form of morphea on
      the scalp and its trichoscopic features have not been described yet. We report 2
      adult women with LSCS with distinct dermoscopic findings. They both had an
      atrophic well-defined linear patch of alopecia on the frontotemporal scalp.
      Dermoscopy showed loss of follicular openings on a whitish skin surface;
      scattered black dots, broken hairs, and pili torti; and short thick linear and
      branching tortuous vessels on the periphery of the lesion. Pathology confirmed
      the diagnosis of LSCS in the 2 cases. This description of dermoscopic features in
      LSCS on the scalp may help in the early diagnosis of the disease.

PMID- 29457012
TI  - Impact of Folliculitis Decalvans on Quality of Life and Subjective Perception of
      Disease.
AB  - Folliculitis decalvans (FD) is a primary neutrophilic scarring alopecia
      characterized by perifollicular papules, crusts, and pustules frequently located
      on the vertex. FD may affect young men and women. Since it may lead to hair loss,
      it can have a negative impact on patients' quality of life. Nevertheless, studies
      have focused on clinical, prognostic, and therapeutic aspects without considering
      the psychological impact of FD. In our study, we found that FD patients
      experienced a considerable impact on their quality of life. Interestingly, almost
      half of the patients considered that their alopecia was related to a poor medical
      care in their past. To our knowledge, this is the first description of the impact
      of FD on patients' quality of life, and it highlights the importance of
      psychological support for these patients.

PMID- 29457013
TI  - Cicatricial Alopecia after a Surgical Procedure.

PMID- 29457014
TI  - Hair That Is Difficult to Manage in a Hispanic Girl.

PMID- 29457016
TI  - Red Dots in a Net-Like Pattern on the Upper Chest: A Novel Clinical Observation
      in Frontal Fibrosing Alopecia and Fibrosing Alopecia in Pattern Distribution.

PMID- 29457015
TI  - Solitary Digital Nodule in an Infant.

PMID- 29457017
TI  - Distinct Trichoscopic Features of the Sideburns in Frontal Fibrosing Alopecia
      Compared to the Frontotemporal Scalp.
AB  - The trichoscopic features of frontal fibrosing alopecia (FFA) have been described
      in the frontotemporal area, yet there is no data detailing the trichoscopic
      features of the sideburns, which can be the initial or exclusive area of
      involvement. In this retrospective cohort study, 236 trichoscopic images of the
      frontotemporal and sideburn area obtained via dry trichoscopy from patients with
      biopsy-proven FFA were examined by two independent researchers to determine the
      trichoscopic features of FFA in the sideburns. The images of the sideburns were
      compared to 44 trichoscopic images of 11 healthy volunteers with intact
      sideburns. Transparent proximal hair emergence surrounded by patches of paler
      smooth skin was the most prominent finding in the sideburns. Peripilar casts and
      peripilar erythema were rare in the sideburns compared to the frontotemporal
      area. Although less common, transparent proximal hair emergence was also seen in
      the sideburns of healthy controls, yet it was shorter and restricted to
      individual hairs. Early FFA presenting exclusively or mostly with sideburn
      involvement should not be missed due to absence of peripilar casts and peripilar
      erythema. Dermoscopy-guided biopsy obtained from hair shafts with transparent
      proximal hair emergence should be considered to make the diagnosis in this
      location.

PMID- 29457018
TI  - Nail Changes in Early Mycosis Fungoides.
AB  - Background: Mycosis fungoides (MF) has a wide range of clinical presentations and
      it has been reported rarely to involve the nail apparatus. Objective: We intended
      to evaluate the frequency and characteristics of nail changes in patients with
      biopsy-proven MF. Methods: A retrospective analysis of 60 patients with MF who
      were evaluated at our cancer center from 2013 to 2014 was performed to identify
      patients with nail changes. Histological examinations of the skin around the nail
      apparatus were obtained from 10 patients with periungual skin erythema and
      scaling. Results: In 45 patients out of 60 cases, the skin around the nail
      apparatus was normal, and only in 5 patients of these 45 cases, nail changes were
      detected. These changes included leukonychia, longitudinal ridging, nail
      thickening, and opacity. In the remaining 15 patients, erythema and scaling was
      observed in periungual skin, and 13 of them demonstrated nail changes including
      longitudinal ridging, nail thickening, fragility of the nail plate, subungual
      hyperkeratosis, pigmented nail band, Beau's lines, onychomadesis, koilonychia,
      nail thinning, distal notching, subungual debris, leukonychia, and pitting. In
      biopsies of periungual skin, none of 10 cases revealed histological findings
      consistent with MF. Conclusions: Evidence of nail changes was observed in 18
      cases (30%). The most common nail changes detected in MF patients included
      longitudinal ridging, nail thickening, nail fragility, and leukonychia.

PMID- 29457019
TI  - Platelet-Rich Plasma in the Treatment of Hair Disorders.

PMID- 29457020
TI  - Infective Endocarditis Associated with Streptococcal Toxic Shock Syndrome due to
      Streptococcus dysgalactiae subsp. equisimilis Infection in a Hemodialysis
      Patient.
AB  - The risk of infective endocarditis in chronic hemodialysis patients is markedly
      higher than that in the general population. We report the first case of a
      hemodialysis patient with infective endocarditis caused by Streptococcus
      dysgalactiae subsp. equisimilis (SDSE) who presented with streptococcal toxic
      shock syndrome. In the last decade, there has been an increase in the incidence
      of SDSE infections. Therefore, it is important to recognize SDSE as a possible
      causative agent of infective endocarditis in an immunocompromised population,
      such as hemodialysis patients.

PMID- 29457021
TI  - Difficult Renal Pathological Classification in a Case of Pediatric Nephrotic
      Syndrome.
AB  - The underlying histopathology is very important in determining patient
      management, as the histopathology usually has direct repercussions on the
      treatment response and clinical course. However, the impact of the method used to
      assess renal biopsies, i.e., light microscopy (LM), immunofluorescence (IF), and
      electron microscopy (EM), on the occurrence of a difficult biopsy classification
      in the native kidneys of pediatric nephrotic patients is unknown. A 12-month-old
      Japanese boy was diagnosed with nephrotic syndrome (NS); he was administered
      prednisolone (60 mg/m2/day), and a continuous albumin infusion was started. A
      renal biopsy using LM revealed minimal change. However, an IF study showed
      granular staining for immunoglobulin G along the glomerular basement membrane.
      Therefore, he was diagnosed with membranous nephropathy (MN). As his proteinuria
      was so severe, we started immunosuppressant therapy and continued the albumin
      infusion for more than 2 months. However, he did not attain complete remission. A
      month later, EM examination of his renal biopsy showed extensive foot process
      fusion without electron-dense deposits. Although the result of the IF study
      suggested MN, the results of the LM and EM studies indicated minimal change. We
      finally diagnosed the patient with minimal change NS, in consideration of his
      clinical condition and course. Because of the failure of previous treatments,
      pulse steroid therapy was started. After five rounds of therapy the patient
      attained complete remission. A difficult renal biopsy finding classification,
      dependent on the diagnostic method used, might occur in the native kidneys of
      pediatric nephrotic patients. Therefore, a diagnosis should be made after
      considering all renal biopsy findings and the clinical course.

PMID- 29457022
TI  - A Case Report of Compound Heterozygous CYP24A1 Mutations Leading to
      Nephrolithiasis Successfully Treated with Ketoconazole.
AB  - CYP24A1 is an enzyme that inactivates vitamin D. Loss-of-function mutations in
      this enzyme are rare but have been linked with idiopathic infantile hypercalcemia
      as well as adult-onset nephrocalcinosis and nephrolithiasis. Genetic testing for
      this mutation should be considered in the presence of calciuria, elevated serum
      calcium, elevated 1,25-dihydroxyvitamin D, and suppressed parathyroid hormone. We
      present a case with these lab findings as well as an elevated 25-hydroxyvitamin
      D/24,25-dihydroxyvitamin D ratio in whom compound heterozygous CYP24A1 mutations
      were found. His hypercalciuria resolved and 1,25-vitamin D level improved with
      ketoconazole treatment. We suggest that it is clinically important to identify
      patients with this phenotype as testing and treatment options are available which
      could reduce progression to chronic kidney disease in this population.

PMID- 29457023
TI  - Effect of Zinc Supplementation on Maintenance Hemodialysis Patients: A Systematic
      Review and Meta-Analysis of 15 Randomized Controlled Trials.
AB  - We aimed to examine the effects of zinc supplementation on nutritional status,
      lipid profile, and antioxidant and anti-inflammatory therapies in maintenance
      hemodialysis (MHD) patients. We performed a systematic review and meta-analysis
      of randomized, controlled clinical trials of zinc supplementation. Metaregression
      analyses were utilized to determine the cause of discrepancy. Begg and Egger
      tests were performed to assess publication bias. Subgroup analysis was utilized
      to investigate the effects of zinc supplementation in certain conditions. In the
      crude pooled results, we found that zinc supplementation resulted in higher serum
      zinc levels (weighted mean difference [WMD] = 28.489; P < 0.001), higher dietary
      protein intake (WMD = 8.012; P < 0.001), higher superoxide dismutase levels (WMD
      = 357.568; P = 0.001), and lower levels of C-reactive protein (WMD = -8.618; P =
      0.015) and malondialdehyde (WMD = -1.275; P < 0.001). The results showed no
      differences in lipid profile. In the metaregression analysis, we found that serum
      zinc levels correlated positively with intervention time (beta = 0.272; P =
      0.042) and varied greatly by ethnicity (P = 0.023). Results from Begg and Egger
      tests showed that there was no significant bias in our meta-analysis (P > 0.1).
      Results of subgroup analysis supported the above results. Our analysis shows that
      zinc supplementation may benefit the nutritional status of MHD patients and show
      a time-effect relationship.

PMID- 29457024
TI  - Role of FGF23 in Pediatric Hypercalciuria.
AB  - Background: This study explored the possible role of FGF23 in pediatric
      hypercalciuria. Methods: Plasma FGF23 was measured in 29 controls and 58 children
      and adolescents with hypercalciuria: 24 before treatment (Pre-Treated) and 34
      after 6 months of treatment (Treated). Hypercalciuric patients also measured
      serum PTH hormone, 25(OH)vitD, phosphate, calcium, creatinine, and 24 h urine
      calcium, phosphate, and creatinine. Results: There were no differences in age,
      gender, ethnicity, or body mass index either between controls and patients, or
      between Pre-Treated and Treated patients. Median plasma FGF23 in controls was 72
      compared with all patients, 58 RU/mL (p = 0.0019). However, whereas FGF23 in Pre
      Treated patients, 73 RU/mL, was not different from controls, in Treated patients
      it was 50 RU/mL, significantly lower than in both controls (p < 0.0001) and Pre
      Treated patients (p = 0.02). In all patients, there was a correlation between
      FGF23 and urinary calcium (r = 0.325; p = 0.0014). Treated patients had
      significantly lower urinary calcium (p < 0.0001), higher TP/GFR (p < 0.001), and
      higher serum phosphate (p = 0.007) versus Pre-Treated patients. Conclusions:
      Pharmacological treatment of hypercalciuric patients resulted in significantly
      lower urinary calcium excretion, lower serum FGF23, and elevated TP/GFR and serum
      phosphate concentration, without significant changes in PTH. Further studies are
      indicated. This trial is registered with Clinical Registration Number RBR 8W27X5.

PMID- 29457025
TI  - LPA Gene Polymorphisms and Gene Expression Associated with Coronary Artery
      Disease.
AB  - The aim of our study was to investigate the influence of LPA gene polymorphisms
      for CAD risk and Lp(a) in a case-control study of Chinese Han population. In
      addition, we further analyzed the effect of LPA gene expression on plasma levels
      of Lp(a) and CAD risk. First, five SNPs (rs1367211, rs3127596, rs6415085,
      rs9347438, and rs9364559) in LPA gene were genotyped using the SEQUENOM Mass
      ARRAY system in two groups. Second, we used quantitative real-time PCR to examine
      the mRNA expression levels of LPA gene in 92 cases and 32 controls. Results
      showed that the frequency of rs6415085-T allele was significantly higher in case
      group than that in control group (P < 0.05). Haplotypes were not associated with
      CAD risk (P > 0.05). And cases with the TT/TG genotype had significantly higher
      plasma Lp(a) levels compared with those that have the rs6415085 GG genotype (P <
      0.05). Additionally, the mRNA expression levels in case group are significantly
      higher than that in control group (P < 0.05). Our study confirmed that rs6415085
      was associated with CAD and increased plasma Lp(a) levels. And increased mRNA
      expression level of LPA gene may be a mechanism in development of CAD.

PMID- 29457026
TI  - Antibiotic-Related Adverse Drug Reactions at a Tertiary Care Hospital in South
      Korea.
AB  - Background: Adverse drug reactions (ADRs) are any unwanted/uncomfortable effects
      from medication resulting in physical, mental, and functional injuries.
      Antibiotics account for up to 40.9% of ADRs and are associated with several
      serious outcomes. However, few reports on ADRs have evaluated only antimicrobial
      agents. In this study, we investigated antibiotic-related ADRs at a tertiary care
      hospital in South Korea. Methods: This is a retrospective cohort study that
      evaluated ADRs to antibiotics that were reported at a 2400-bed tertiary care
      hospital in 2015. ADRs reported by physicians, pharmacists, and nurses were
      reviewed. Clinical information reported ADRs, type of antibiotic, causality
      assessment, and complications were evaluated. Results: 1,277 (62.8%) patients
      were considered antibiotic-related ADRs based on the World Health Organization
      Uppsala Monitoring Center criteria (certain, 2.2%; probable, 35.7%; and possible,
      62.1%). Totally, 44 (3.4%) patients experienced serious ADRs. Penicillin and
      quinolones were the most common drugs reported to induce ADRs (both 16.0%),
      followed by third-generation cephalosporins (14.9%). The most frequently
      experienced side effects were skin manifestations (45.1%) followed by
      gastrointestinal disorders (32.6%). Conclusion: Penicillin and quinolones are the
      most common causative antibiotics for ADRs and skin manifestations were the most
      frequently experienced symptom.

PMID- 29457027
TI  - Oxidative Modification of Biomolecules in the Nonstimulated and Stimulated Saliva
      of Patients with Morbid Obesity Treated with Bariatric Surgery.
AB  - Morbid obesity leads to progressive failure of many human organs and systems;
      however, the role of oxidative damage to salivary composition is still unknown in
      the obese patients. In this study, we assessed the effect of bariatric surgery on
      oxidative damage in nonstimulated (NS) and stimulated (S) whole saliva. The study
      included 47 subjects with morbid obesity as well as 47 age- and gender-matched
      healthy volunteers. Oxidative modifications to lipids (4-hydroxynonenal (4-HNE)
      and 8-isoprostanes (8-isoP)), proteins (advanced oxidation protein products
      (AOPP) and protein carbonyl groups (PC)), and DNA (8-hydroxy-D-guanosine (8
      OHdG)) were analyzed in morbidly obese patients before and after bariatric
      surgery as well as in the healthy controls. The concentrations of 8-isoP, AOPP,
      PC, and 8-OHdG were significantly higher in both NS and S of patients with morbid
      obesity than in the control patients and compared to the results obtained 6
      months after bariatric surgery. The levels of oxidative damage markers were also
      higher in S versus NS of morbidly obese patients. In summary, morbid obesity is
      associated with oxidative damage to salivary proteins, lipids, and DNA, while
      bariatric treatment generally lowers the levels of salivary oxidative damage.

PMID- 29457028
TI  - Effect of Dietary Chestnut or Quebracho Tannin Supplementation on Microbial
      Community and Fatty Acid Profile in the Rumen of Dairy Ewes.
AB  - Ruminants derived products have a prominent role in diets and economy worldwide;
      therefore, the capability to control the rumen microbial ecosystem, for
      ameliorating their quality, is of fundamental importance in the livestock sector.
      The aim of this study was to evaluate the effect of dietary supplementation with
      chestnut and quebracho tannins on microbial community and fatty acid profile, in
      the rumen fluid of dairy ewes. Multivariate analysis of PCR-DGGE profiles of
      rumen microbial communities showed a correlation among the presence of chestnut
      or quebracho in the diet, the specific Butyrivibrio group DGGE profiles, the
      increase in 18:3 cis9, cis12, and cis15; 18:2 cis9 and cis12; 18:2 cis9 and
      trans11; 18:2 trans11 and cis15; and 18:1 trans11 content, and the decrease in
      18:0 concentration. Phylogenetic analysis of DGGE band sequences revealed the
      presence of bacteria representatives related to the genera Hungatella,
      Ruminococcus, and Eubacterium and unclassified Lachnospiraceae family members,
      suggesting that these taxa could be affected by tannins presence in the diets.
      The results of this study showed that tannins from chestnut and quebracho can
      reduce the biohydrogenation of unsaturated fatty acids through changes in rumen
      microbial communities.

PMID- 29457029
TI  - Preventive Effect of Cashew-Derived Protein Hydrolysate with High Fiber on
      Cerebral Ischemia.
AB  - This study aimed to determine the protective effect of cashew nut-derived protein
      hydrolysate with high dietary fiber (AO) in cerebral ischemic rats induced by the
      occlusion of right middle cerebral artery (Rt.MCAO). Acute toxicity was
      determined and data showed that LD50 of AO > 5000 mg/kg BW. To determine the
      cerebroprotective effect of AO, male Wistar rats were orally given AO at doses of
      2, 10, and 50 mg/kg for 14 days and subjected to Rt.MCAO. Brain infarction
      volume, neurological score, spatial memory, serum lipid profiles, and C-reactive
      protein together with the brain oxidative stress status were assessed. All doses
      of AO significantly decreased brain infarction in cortex, hippocampus, and
      striatum together with the decreased oxidative stress status. The improvement of
      spatial memory and serum C-reactive protein were also observed in MCAO rats which
      received AO at all doses. In addition, the decreased serum cholesterol, TG, and
      LDL but increased HDL were observed in MCAO rats which received high dose of AO.
      Taken all together, AO is the potential protectant against cerebral ischemia. The
      improvement of oxidative stress, inflammation, and dyslipidemia might play roles
      in the actions. However, further researches are required to understand the
      precise underlying mechanism.

PMID- 29457030
TI  - The Relationship of Motor Coordination, Visual Perception, and Executive Function
      to the Development of 4-6-Year-Old Chinese Preschoolers' Visual Motor Integration
      Skills.
AB  - Visual motor integration (VMI) is a vital ability in childhood development, which
      is associated with the performance of many functional skills. By using the Beery
      Developmental Test Package and Executive Function Tasks, the present study
      explored the VMI development and its factors (visual perception, motor
      coordination, and executive function) among 151 Chinese preschoolers from 4 to 6
      years. Results indicated that the VMI skills of children increased quickly at 4
      years and peaked at 5 years and decreased at around 5 to 6 years. Motor
      coordination and cognitive flexibility were related to the VMI development of
      children from 4 to 6 years. Visual perception was associated with the VMI
      development at early 4 years and inhibitory control was also associated with it
      among 4-year-old and the beginning of 5-year-old children. Working memory had no
      impact on the VMI. In conclusion, the development of VMI skills among children in
      preschool was not stable but changed dynamically in this study. Meanwhile the
      factors of the VMI worked in different age range for preschoolers. These findings
      may give some guidance to researchers or health professionals on improving
      children's VMI skills in their early childhood.

PMID- 29457032
TI  - Corrigendum to "Preservation of Myocardial Perfusion and Function by Keeping
      Hypertrophied Heart Empty and Beating for Valve Surgery: An In Vivo MR Study of
      Pig Hearts".
AB  - [This corrects the article DOI: 10.1155/2017/4107587.].

PMID- 29457031
TI  - The STARTEC Decision Support Tool for Better Tradeoffs between Food Safety,
      Quality, Nutrition, and Costs in Production of Advanced Ready-to-Eat Foods.
AB  - A prototype decision support IT-tool for the food industry was developed in the
      STARTEC project. Typical processes and decision steps were mapped using real life
      production scenarios of participating food companies manufacturing complex ready
      to-eat foods. Companies looked for a more integrated approach when making food
      safety decisions that would align with existing HACCP systems. The tool was
      designed with shelf life assessments and data on safety, quality, and costs,
      using a pasta salad meal as a case product. The process flow chart was used as
      starting point, with simulation options at each process step. Key parameters like
      pH, water activity, costs of ingredients and salaries, and default models for
      calculations of Listeria monocytogenes, quality scores, and vitamin C, were
      placed in an interactive database. Customization of the models and settings was
      possible on the user-interface. The simulation module outputs were provided as
      detailed curves or categorized as "good"; "sufficient"; or "corrective action
      needed" based on threshold limit values set by the user. Possible corrective
      actions were suggested by the system. The tool was tested and approved by end
      users based on selected ready-to-eat food products. Compared to other decision
      support tools, the STARTEC-tool is product-specific and multidisciplinary and
      includes interpretation and targeted recommendations for end-users.

PMID- 29457033
TI  - Measurement of Gender Differences of Gastrocnemius Muscle and Tendon Using
      Sonomyography during Calf Raises: A Pilot Study.
AB  - Skeletal muscles are essential to the gender-specific characteristics of human
      movements. Sonomyography, a new signal for quantifying muscle activation, is of
      great benefit to understand muscle function through monitoring the real-time
      muscle architectural changes. The purpose of this pilot study was to investigate
      gender differences in the architectural changes of gastronomies muscle and tendon
      by using sonomyography during performing two-legged calf raising exercises. A
      motion analysis system was developed to extract sonomyography from ultrasound
      images together with kinematic and kinetic measurements. Tiny fascicle length
      changes among seven male subjects were observed at the initial part of calf
      raising, whereas the fascicle of seven female subjects shortened immediately.
      This result suggested that men would generate higher mechanical power output of
      plantar flexors to regulate their heavier body mass. In addition, the larger
      regression coefficient between the fascicle length and muscle force for the male
      subjects implied that higher muscle stiffness for the men was required in demand
      of maintaining their heavier body economically. The findings from the current
      study suggested that the body mass might play a factor in the gender difference
      in structural changes of muscle and tendon during motion. The sonomyography may
      provide valuable information in the understanding of the gender difference in
      human movements.

PMID- 29457034
TI  - Unilateral Arm Crank Exercise Test for Assessing Cardiorespiratory Fitness in
      Individuals with Hemiparetic Stroke.
AB  - Cardiorespiratory fitness assessment with leg cycle exercise testing may be
      influenced by motor impairments in the paretic lower extremity. Hence, this study
      examined the usefulness of a unilateral arm crank exercise test to assess
      cardiorespiratory fitness in individuals with stroke, including sixteen
      individuals with hemiparetic stroke (mean +/- SD age, 56.4 +/- 7.5 years) and 12
      age- and sex-matched healthy controls. Participants performed the unilateral arm
      crank and leg cycle exercise tests to measure oxygen consumption ([Formula: see
      text]O2) and heart rate at peak exercise. The [Formula: see text]O2 at peak
      exercise during the unilateral arm crank exercise test was significantly lower in
      the stroke group than in the control group (p < 0.001). In the stroke group, the
      heart rate at peak exercise during the unilateral arm crank exercise test did not
      significantly correlate with the Brunnstrom recovery stages of the lower
      extremity (p = 0.137), whereas there was a significant correlation during the leg
      cycle exercise test (rho = 0.775, p < 0.001). The unilateral arm crank exercise
      test can detect the deterioration of cardiorespiratory fitness independently of
      lower extremity motor impairment severity in individuals with hemiparetic stroke.
      This study is registered with UMIN000014733.

PMID- 29457035
TI  - Impact of Elevated Circulating Histones on Systemic Inflammation after
      Radiofrequency Ablation in Lung Cancer Patients.
AB  - Background: This study investigated the changes of circulating histones following
      radiofrequency ablation (RFA) in lung cancer patients and their impact on
      systemic inflammation. Methods: Serial blood samples were obtained from a total
      of 65 primary and metastatic lung cancer patients undergoing RFA at 2 time
      points: pre-RFA and post-RFA within 48 h. Circulating histones, myeloperoxidase
      (MPO), and multiple inflammatory cytokines were measured. Moreover, the patient's
      sera were incubated overnight with human monocytic U937 cells in the presence or
      absence of anti-histone antibody, and cytokine production was evaluated. Results:
      Compared to pre-RFA, there was a significant increase in circulating histones
      within 48 h after RFA, along with an elevation of MPO and several canonical
      inflammatory cytokines. Circulating histones were correlated with these
      inflammatory markers. Notably, compared to the sera obtained before RFA, the
      patients' post-RFA sera significantly stimulated cytokine production in the
      supernatant of U937 cells, which could be prevented by anti-histone antibody,
      thereby confirming a cause-effect relationship between circulating histones and
      systemic inflammation. Conclusions: This study showed that circulating histones
      may serve as a marker indicating RFA-related systemic inflammation as well as
      represent a therapeutic target for resolution of inflammation.

PMID- 29457036
TI  - Zoledronic Acid Regulates Autophagy and Induces Apoptosis in Colon Cancer Cell
      Line CT26.
AB  - Zoledronic acid (ZOL) is the third generation of bisphosphonates, which can
      inhibit many tumors growth, especially to inhibit the growth of colon cancer.
      However, the molecular mechanism is still very mysterious. In this study, we
      observed that ZOL could regulate CT26 colon cancer cells autophagy, promote CT26
      cells apoptosis, and inhibit CT26 cells proliferation. Western blotting analysis
      showed that proapoptosis protein caspase-3 was basically unchanged, whereas the
      expression of the activated caspase-3 was significantly increased, after CT26
      cells were treated with different doses of zoledronic acid. Western blot also
      showed that ZOL could significantly affect the expression of p-p53 and autophagy
      related proteins beclin-1 and p62. In conclusion, the antitumor effect of ZOL on
      CT26 colon cancer cells in vitro is achieved by apoptosis induction and autophagy
      regulation, resulting in inhibition of cell proliferation.

PMID- 29457037
TI  - Decreased Expression of Semaphorin3A/Neuropilin-1 Signaling Axis in Apical
      Periodontitis.
AB  - Apical periodontitis (AP) is a chronic infection of endodontic origin accompanied
      with bone destruction around the apical region. Semaphorin3A (Sema3A) and
      neuropilin-1 (Nrp1) are regarded as a pair of immune regulators in bone
      metabolism. In this study, we firstly investigated the expression pattern of
      Sema3A/Nrp1 in apical periodontitis and its correlation with bone destruction.
      Using rat animal model, we analysed the level of mandibular bone destruction and
      the expression of Sema3A/Nrp1 on days 0, 7, 14, 21, 28, and 35 after pulp
      exposure. In addition, clinical samples from apical periodontitis patients were
      obtained to analyse the expression of Sema3A/Nrp1. These results indicated that
      the bone destruction level expanded from days 7 to 35. The number of positive
      cells and level of mRNA expression of Sema3A/Nrp1 were significantly decreased
      from days 7 to 35, with a negative correlation with bone destruction. Moreover,
      expression of Sema3A/Nrp1 in the AP group was reduced compared to the control
      group of clinical samples. In conclusion, decreased expression of Sema3A/Nrp1 was
      observed in periapical lesions and is potentially involved in the bone resorption
      of the periapical area, suggesting that Sema3A/Nrp1 may contribute to the
      pathological development of apical periodontitis.

PMID- 29457038
TI  - Insulin Resistance and Its Association with Metabolic Syndrome in Korean
      Children.
AB  - Background: This study investigated the association between insulin resistance
      (IR) and metabolic syndrome (MetS) in children. Methods: A cross-sectional study
      involving 1036 healthy children aged between 7 and 13 years was conducted.
      Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as an
      index of IR. Participants were classified according to the HOMA-IR quartiles.
      Results: Incremental, linear trends were found in age (p < 0.001), body mass
      index (BMI) (p < 0.001), body fat (p < 0.001), waist circumference (p < 0.001),
      resting blood pressures (BP) (p < 0.001), triglycerides (TG) (p < 0.001), total
      cholesterol (TC) (p < 0.001), high density lipoprotein-cholesterol (HDL-C) (p <
      0.001), FBG (p < 0.001), and insulin (<0.001) according to incremental HOMA-IR
      categories (from the 1st to 4th quartile). Compared with children in the 1st HOMA
      IR quartile, children in the 4th HOMA-IR quartile had significantly higher odd
      ratios (ORs) of abnormalities in systolic (p = 0.051) and diastolic BP (p =
      0.005), FBG (p < 0.001), TG (p < 0.001), TC (p = 0.016), and HDL-C (p = 0.006)
      even after adjustments for age, gender, BMI, and body fat percentage. Children in
      the 3rd HOMA-IR quartile had significant abnormalities in FBG (p < 0.001), TG (p
      = 0.001), and HDL-C (p = 0.010) even after adjustments for the covariates.
      Conclusion: The current findings suggest that IR is significantly associated with
      the clustering of MetS risk factors in children in Korea.

PMID- 29457040
TI  - A fluorescence assay for detecting amyloid-beta using the cytomegalovirus
      enhancer/promoter.
AB  - Robust assays for detecting the effects of elevated concentrations of amyloid
      beta (Abeta) may facilitate Alzheimer's disease research. An appropriate assay
      would be high-throughput and enable identification of drugs and genetic mutations
      that block the effects of Abeta, potentially leading to treatments for
      Alzheimer's disease. We discovered that the commonly used cytomegalovirus (CMV)
      enhancer/promoter is sensitive to the effects of Abeta. By combining the CMV
      enhancer/promoter with a fluorescent protein, we created a reporter system that
      produces changes in intracellular fluorescence in response to Abeta. Using
      hippocampal neurons, we quantified the ability of a CMV-fluorescent protein
      recombinant reporter to detect both exogenously applied and overexpressed Abeta.
      This is the first report of a high-throughput enhancer/promoter-based Abeta
      detection method. The reporter is able to detect the effects of elevated
      concentrations of Abeta in a high-throughput fashion, providing a new tool for
      Alzheimer's disease research and important knowledge about the commonly used CMV
      enhancer/promoter.

PMID- 29457039
TI  - Silencing Chitinase Genes Increases Susceptibility of Tetranychus cinnabarinus
      (Boisduval) to Scopoletin.
AB  - The carmine spider mite Tetranychus cinnabarinus is a major pest of crop and
      vegetable plants worldwide. Previous studies have shown that scopoletin is a
      promising acaricidal compound against Tetranychus cinnabarinus. However, the
      acaricidal mechanism of scopoletin remains unclear. In the present study, 12 full
      length cDNAs of chitinase (CHIT) genes from Tetranychus cinnabarinus (designated
      TcCHITs) were cloned and characterized. Although TcCHITs were expressed
      throughout all life stages, their expression levels were significantly
      upregulated during the larval and nymphal stages. TcCHITs were downregulated 24 h
      after treatment with scopoletin and upregulated 24 h after treatment with
      diflubenzuron (DFB, a chitin synthesis inhibitor). Feeding double-stranded RNA
      effectively silenced TcCHIT transcription in Tetranychus cinnabarinus, thus
      increasing its susceptibility to scopoletin but reducing that to DFB. Meanwhile,
      TcCHIT silencing in larvae and adult resulted in an extremely low molting rate
      (7.3%) and high mortality rate (53.3%), respectively, compared with those in the
      control group. CHIT genes are closely related to arthropod survival, molting, and
      development in Tetranychus cinnabarinus, suggesting that acaricidal mechanisms of
      scopoletin and DFB may occur by inhibition and activation of CHIT gene
      expression, respectively. TcCHIT constitutes a possible target of scopoletin and
      DFB in Tetranychus cinnabarinus.

PMID- 29457041
TI  - How to Catch a Smurf? - Ageing and Beyond... In vivo Assessment of Intestinal
      Permeability in Multiple Model Organisms.
AB  - The Smurf Assay (SA) was initially developed in the model organism Drosophila
      melanogaster where a dramatic increase of intestinal permeability has been shown
      to occur during aging (Rera et al., 2011). We have since validated the protocol
      in multiple other model organisms (Dambroise et al., 2016) and have utilized the
      assay to further our understanding of aging (Tricoire and Rera, 2015; Rera et
      al., 2018). The SA has now also been used by other labs to assess intestinal
      barrier permeability (Clark et al., 2015; Katzenberger et al., 2015; Barekat et
      al., 2016; Chakrabarti et al., 2016; Gelino et al., 2016). The SA in itself is
      simple; however, numerous small details can have a considerable impact on its
      experimental validity and subsequent interpretation. Here, we provide a detailed
      update on the SA technique and explain how to catch a Smurf while avoiding the
      most common experimental fallacies.

PMID- 29457042
TI  - Biliary Complications - The "Achilles Heel" of Orthotopic Liver Transplantation.

PMID- 29457043
TI  - Acute (Not Decompensation)-on-Chronic Liver Failure.

PMID- 29457044
TI  - Once upon a Time a Guideline Was Used for the Evaluation of Suspected
      Choledocholithiasis: A Fairy Tale or a Nightmare?

PMID- 29457045
TI  - Efficacy of Endoscopic Retrograde Cholangiopancreatography in the Treatment of
      Biliary Complications following Liver Transplant: 10 Years of a Single-Centre
      Experience.
AB  - Background and Aims: Biliary tract complications following liver transplant
      remain an important source of morbidity and mortality. Endoscopic retrograde
      cholangiopancreatography (ERCP) has become a common therapeutic option before
      other invasive procedures. The aim of this study was to evaluate ERCP efficacy in
      managing this type of complications. Methods: Retrospective study of all patients
      who underwent therapeutic ERCP due to post-liver transplant biliary complications
      between September 2005 and September 2015, at a deceased donor liver
      transplantation centre. Results: Therapeutic ERCP was performed in 120 patients
      (64% men; mean age 46 +/- 14 years). Biliary complications were anastomotic
      strictures (AS) in 70%, non-anastomotic strictures (NAS) in 14%, bile leaks (BL)
      in 5.8%, and bile duct stones (BDS) in 32%. The mean time between liver
      transplant and first ERCP was: 19 +/- 30 months in AS, 17 +/- 30 months in NAS,
      61 +/- 28 months in BDS, and 0.7 +/- 0.6 months in BL (p < 0.001). The number of
      ERCP performed per patient was: 3.8 +/- 2.4 in AS, 3.8 +/- 2.1 in NAS, 1.9 +/- 1
      in BDS, and 1.9 +/- 0.5 in BL (p = 0.003). The duration of the treatment was: 18
      +/- 19 months in AS, 21 +/- 17 months in NAS, 10 +/- 10 months in BDS, and 4 +/-
      3 months in BL (p = 0.064). Overall, biliary complications were successfully
      managed by ERCP in 46% of cases, either as an isolated procedure (43%) or rendez
      vous ERCP (3%). Per complication, ERCP was effective in 39% of AS, in 12% of NAS,
      in 91% of BDS, and in 86% of BL. Globally, the mean follow-up of the successful
      cases was 43 +/- 31 months. Percutaneous transhepatic cholangiography and/or
      surgery were performed in 48% of patients in whom ERCP was unsuccessful. The odds
      ratio for effective endoscopic treatment was 0.2 for NAS (0.057-0.815), 12.4 for
      BDS (1.535-100.9), and 6.9 for BL (0.798-58.95). No statistical significance was
      found for AS (p = 0.247). Conclusions: ERCP allowed the treatment of biliary
      complication in about half of patients, avoiding a more invasive procedure.
      Endoscopic treatment was more effective for BDS and BL.

PMID- 29457046
TI  - Acute-on-Chronic Liver Failure: A Portuguese Single-Center Reference Review.
AB  - : Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute
      deterioration of a patient with cirrhosis, frequently associated with multi-organ
      failure and a high short-term mortality rate. We present a retrospective study
      that aims to characterize the presentation, evolution, and outcome of patients
      diagnosed with ACLF at our center over the last 3 years, with a comparative
      analysis between the group of patients that had ACLF precipitated by infectious
      insults of bacterial origin and the group of those with ACLF triggered by a
      nonbacterial infectious insult; the incidence of acute kidney injury and its
      impact on the prognosis of ACLF was also analyzed. Twenty-nine patients were
      enrolled, the majority of them being male (89.6%), and the mean age was 53 years.
      Fourteen patients (48.3%) developed ACLF due to a bacterial infectious event, and
      9 of them died (64.2%, overall mortality rate 31%); however, no statistical
      significance was found (p < 0.7). Of the remaining 15 patients (51.7%) with
      noninfectious triggers, 11 died (73.3%, overall mortality rate 37.9%); again
      there was no statistical significance (p < 0.7). Twenty-four patients (83%)
      developed acute kidney injury (overall mortality rate 65.5%; p < 0.022) at the 28
      day and 90-day follow-up. Twelve patients had acute kidney injury requiring renal
      replacement therapy (41.37%; overall mortality rate 37.9%; p < 0.043). Hepatic
      transplant was performed in 3 patients, with a 100% survival at the 28-day and 90
      day follow-up (p < 0.023). Higher grades of ACLF were associated with increased
      mortality (p < 0.02; overall mortality 69%). Conclusions: ACLF is a heterogeneous
      syndrome with a variety of precipitant factors and different grades of
      extrahepatic involvement. Most cases will have some degree of renal dysfunction,
      with an increased risk of mortality. Hepatic transplant is an efficient form of
      therapy for this syndrome.

PMID- 29457047
TI  - Performance of the Choledocholithiasis Diagnostic Score in Patients with Acute
      Cholecystitis.
AB  - Introduction: The prevalence of choledocholithiasis among patients with acute
      cholecystitis is estimated to be between 9 and 16.5%. There are no validated
      algorithms to predict choledocholithiasis in this group of patients. Aim: The aim
      of this study was to evaluate the performance of the choledocholithiasis
      diagnostic score proposed by the American Society for Gastrointestinal Endoscopy,
      in patients with acute cholecystitis. Material/Methods: A retrospective cross
      sectional study, covering a 4-year period at a secondary care hospital, was
      performed. All patients with an encoded diagnosis of acute cholecystitis and with
      at least one of the following procedures were included: endoscopic retrograde
      cholangiopancreatography (ERCP), endoscopic ultrasound, magnetic resonance
      cholangiopancreatography, and intraoperative cholangiography. Results: Among
      4,369 patients with the diagnosis of acute cholecystitis, 40 (0.92%) had clinical
      or sonographic suspicion of choledocholithiasis. Their mean age was 68.1 +/- 15
      years, and 22 (55%) were men. Thirty-one of the patients included (77.5%) had a
      high risk of choledocholithiasis, and 9 (22.5%) had an intermediate risk. In 16
      (51.6%) of the 31 patients with a high risk, the diagnosis of choledocholithiasis
      was confirmed. In 2 (22.2%) of the 9 patients with an intermediate risk, the
      diagnosis of choledocholithiasis was also confirmed. The high risk score for
      choledocholithiasis had a positive predictive value of 52% and a sensitivity of
      89%. The intermediate risk score for choledocholithiasis had a positive
      predictive value of 22% and a sensitivity of 11%. Discussion and Conclusions:
      Suspicion of choledocholithiasis in patients with acute cholecystitis was a rare
      event (<1%). The sensitivity of the high risk score was approximately the same as
      found in published series with patients with suspected choledocholithiasis
      overall (86%), while the positive predictive value was substantially lower (52
      vs. 79.8%). Therefore, in patients with acute cholecystitis and suspected
      choledocholithiasis, this score should not be used to screen for common bile duct
      stones, and a sensitive method should be used prior to ERCP.

PMID- 29457049
TI  - Intestinal Obstruction of Uncommon Cause and Point-of-Care Ultrasonography -
      Where Do We Stand?
AB  - Malignant neoplasms of the small bowel, especially from the jejunum, are among
      the rarest types of cancer. Given its location, a delayed diagnosis is frequent
      and sometimes only made in an emergency context. The authors present a case of
      intestinal obstruction, where ultrasonography was pivotal in establishing a
      diagnosis. Point-of-care ultrasonography seems to be particularly sensitive in
      assessing emergency patients with abdominal pain, allowing effective orientation
      and saving human and technical resources.

PMID- 29457048
TI  - Farnesoid X Receptor Expression in Microscopic Colitis: A Potential Role in
      Disease Etiopathogenesis.
AB  - Introduction: Microscopic colitis (MC) is a chronic inflammatory bowel disease
      with unclear etiology. Bile acid (BA) malabsorption has been described in MC
      patients. Farnesoid X receptor (FXR) is the main BA receptor; FXR-mediated
      mechanisms prevent the noxious effects of BA accumulation, preserving the
      integrity of the intestinal epithelial barrier and preventing intestinal
      inflammation. Aim: Our aim was to describe the expression of FXR in patients with
      MC. Methods: Archival formalin-fixed paraffin-embedded samples from the terminal
      ileum, right and left colon were obtained from patients with MC and matched
      controls. Immunohistochemistry was performed and nuclear FXR expression scored in
      a semi-quantitative way. Results: 169 formalin-fixed paraffin-embedded samples
      from 35 patients with MC and 31 controls were retrieved. There was a significant
      reduction of FXR expression in patients with MC versus controls both in the right
      colon (moderate-strong FXR expression: 21.1 vs. 64.3%; p = 0.003) and left colon
      (moderate-strong FXR expression: 8.3 vs. 38.7%; p = 0.027). No significant
      differences in FXR expression were observed in the ileum of patients with MC
      (moderate-strong FXR expression: 76.9 vs. 90.9%; p = 0.5). We found no difference
      in FXR expression between the two types of MC. No association between the degree
      of lymphocyte infiltration or the thickness of collagen band and FXR expression
      was found. Conclusions: Patients with MC present a significantly lower expression
      of FXR in the colon. This could render colonic epithelial cells more susceptible
      to the deleterious effects of BA, contributing to disease pathogenesis and
      symptoms in MC.

PMID- 29457050
TI  - Pelvic Catastrophe after Elastic Band Ligation in an Irradiated Rectum.
AB  - Chronic radiation proctopathy is a frequent complication after both pelvic
      external radiation therapy and brachytherapy and most commonly presents as rectal
      bleeding. Deep rectal ulcers and fistulae are much rarer and more clinically
      challenging consequences. We present the case of a 72-year-old male with a
      history of prostate adenocarcinoma treated with brachytherapy, who was referred
      to our institution due to a deep painful rectal ulcer refractory to medical
      treatment. The ulcer presented shortly after a haemorrhoid elastic band ligation
      and progressed to rectourethral fistulisation despite both faecal and urinary
      diversion. Our case demonstrates the importance of favouring a conservative
      approach when dealing with an irradiated rectum.

PMID- 29457051
TI  - Signet Ring Cell Carcinoma, Ileal Crohn Disease or Both? - A Case of Diagnostic
      Challenge.
AB  - Signet ring cell carcinoma is a rare form of adenocarcinoma that predominantly
      affects the stomach. Signet ring cell carcinoma originated from the ileum is
      extremely rare and the prognosis is poor. We present a case of small bowel
      obstruction with features suggesting Crohn disease of the ileum. The symptoms
      were chronic diarrhea and abdominal pain with a family history of inflammatory
      bowel disease. The patient underwent surgery and histopathology revealed both
      aspects of signet ring cell carcinoma and Crohn disease of the ileum. An
      association between long-standing inflammation and the development of this
      subtype of tumor has been proposed but there are no established surveillance
      guidelines for small bowel neoplasm in inflammatory bowel disease.

PMID- 29457052
TI  - An Unexpected Abdominal Radiographic Finding: Chilaiditi Sign.

PMID- 29457053
TI  - Increased subjective experience of non-target emotions in patients with
      frontotemporal dementia and Alzheimer's disease.
AB  - Although laboratory procedures are designed to produce specific emotions,
      participants often experience mixed emotions (i.e., target and non-target
      emotions). We examined non-target emotions in patients with frontotemporal
      dementia (FTD), Alzheimer's disease (AD), other neurodegenerative diseases, and
      healthy controls. Participants watched film clips designed to produce three
      target emotions. Subjective experience of non-target emotions was assessed and
      emotional facial expressions were coded. Compared to patients with other
      neurodegenerative diseases and healthy controls, FTD patients reported more
      positive and negative non-target emotions, whereas AD patients reported more
      positive non-target emotions. There were no group differences in facial
      expressions of non-target emotions. We interpret these findings as reflecting
      deficits in processing interoceptive and contextual information resulting from
      neurodegeneration in brain regions critical for creating subjective emotional
      experience.

PMID- 29457054
TI  - Towards a whole brain model of Perceptual Learning.
AB  - A hallmark of modern Perceptual Learning (PL) is the extent to which learning is
      specific to the trained stimuli. Such specificity to orientation, spatial
      location and even eye of training has been used as psychophysical evidence of the
      neural basis of learning. This argument that specificity of PL implies
      regionalization of brain plasticity implicitly assumes that examination of a
      singular locus of PL is an appropriate approach to understand learning. However,
      recent research shows that learning effects once thought to be specific depend on
      subtleties of the training paradigm and that within even a simple training
      procedure there are multiple aspects of the task and stimuli that are learned
      simultaneously. Here, we suggest that learning on any task involves a broad
      network of brain regions undergoing changes in representations, read-out weights,
      decision rules, attention and feedback processes as well as oculomotor changes.
      However, importantly, the distribution of learning across the neural system
      depends upon the details of the training procedure and the characterstics of the
      individual being trained. We propose that to advance our understanding of PL, the
      field must move towards understanding how distributed brain processes jointly
      contribute to behavioral learning effects.

PMID- 29457055
TI  - Tuberculin skin test conversion and primary progressive tuberculosis disease in
      the first 5 years of life: a birth cohort study from Cape Town, South Africa.
AB  - Background: Tuberculosis is a leading cause of global childhood mortality.
      However, the epidemiology and burden of tuberculosis in infancy is not well
      understood. We aimed to investigate tuberculin skin test conversion and
      tuberculosis in the Drakenstein Child Health study, a South African birth cohort
      in a community in which tuberculosis incidence is hyperendemic. Methods: In this
      prospective birth cohort study, we enrolled pregnant women older than 18 years
      who were between 20 and 28 weeks' gestation and who were attending antenatal care
      in a peri-urban, impoverished South African setting. We followed up their
      children for tuberculosis from birth until April 1, 2017, or age 5 years. All
      children received BCG vaccination at birth. Tuberculin skin tests were
      administered to children at 6, 12, 24, 36, 48, and 60 months of age, and at the
      time of a lower respiratory tract infection. An induration reaction of 10 mm or
      more was considered to be a tuberculin skin test conversion. To prevent boosting,
      we censored children with a reactive, negative tuberculin skin test. Findings:
      Among 915 mother-child pairs (201 [22%] HIV-positive mothers and two [<1%] HIV
      positive children), 147 (16%) children had tuberculin skin test conversion, with
      increasing cumulative hazard with age (0.08 at 6 months, 0.17 at 12 months, 0.22
      at 24 months, and 0.37 at age 36 months). For every 100 child-years, the
      incidence was 11.8 (95% CI 10.0-13.8) for tuberculin skin test conversion, 2.9
      (2.4-3.7) for all diagnosed tuberculosis, and 0.7 (0.4-1.0) for microbiologically
      confirmed tuberculosis. Isoniazid preventive therapy was effective in averting
      disease progression (adjusted hazard ratio 0.22, 95% CI 0.08-0.63; p<0.0001).
      Children with a lower respiratory tract infection were significantly more likely
      to also have tuberculosis than were those without one (2.27, 1.42-3.62;
      p<0.0001). Interpretation: Greater focus should be placed on the first years of
      life as a period of high burden of transmission and clinical expression of
      tuberculosis infection and disease. Multifaceted interventions, such as isoniazid
      preventive therapy and tuberculosis screening of infants with LRTIs, beginning
      early in life, are needed in high-burden settings. Funding: Bill & Melinda Gates
      Foundation, Medical Research Council South Africa, and National Research
      Foundation South Africa.

PMID- 29457056
TI  - When can we give general anesthesia to an infant with anticipated difficult
      airway management caused by facial vascular malformation?
AB  - A 13-month-old infant weighing 8.3 kg with a height of 72.3 cm visited our
      hospital for surgical resection of facial vascular malformation detected at
      birth. Because we anticipated the patient would have difficult airway management
      and massive perioperative bleeding, we postponed surgery to discuss the
      appropriate timing and general anesthesia approach with anesthesiologists at
      other institutions, while explaining the risk of general anesthesia and bleeding
      to the parents. When the patient was 21 months old and 10 kg, he started bleeding
      while undressing, when his lips touched his clothes. Because the cricothyroid
      membrane puncture kit (QuickTrach ChildTM (VBM Medizintechnik GmbH, Sulz am
      Neckar, Germany)) can be used on infants weighing over 10 kg, we decided to give
      him general anesthesia. The infant was successfully intubated by AirwayscopeTM
      and the lesion was surgically removed in accordance with the preoperative plan.
      The procedure took 65 min and created 8 g of bleeding. The infant had no
      postoperative bleeding or respiratory complications. There is no data on the
      timing of safe anesthesia management in infants with difficult airway management.
      Thus, taking the time to discuss the case with surgeons, other anesthesiologists,
      and the parents can be helpful.

PMID- 29457057
TI  - Low preoperative regional cerebral oxygen saturation in hemodialysis patients.
AB  - Background: Regional cerebral oxygen saturation (rSO2) monitoring by near
      infrared spectroscopy provides valuable information regarding cerebral oxygen
      delivery, and it has been increasingly used in cardiovascular surgery. Although
      it has been shown that dialysis-dependent patients [hemodialysis (HD) patients]
      suffer from low cerebral perfusion, limited information is available on cerebral
      tissue oxygenation levels in HD patients. Findings: In this retrospective study,
      the preoperative rSO2 values in 9 HD patients undergoing coronary artery bypass
      graft surgery were compared with those in 40 non-HD patients. HD patients had
      lower preoperative rSO2 values than non-HD patients (median: 46 vs. 68%,
      respectively, P < 0.001). Despite adjusting for age, hemoglobin concentration,
      and left ventricular ejection fraction using multivariable linear regression, HD
      showed a strong association with low rSO2 (estimated coefficient: -20.4, P <
      0.001). Conclusions: HD showed a strong association with low preoperative rSO2
      values in patients undergoing coronary artery bypass graft surgery, even after
      adjusting for known factors that affect rSO2 values, including age, hemoglobin
      concentration, and cardiac systolic function. Further research is required to
      elucidate the mechanisms decreasing rSO2 values in HD patients.

PMID- 29457058
TI  - Coronary ostial stenosis detected by transesophageal echocardiography after
      aortic valve replacement: a case report.
AB  - Background: Coronary ostial stenosis is a life-threatening complication of aortic
      valve replacement (AVR). Clinical symptoms usually appear within the first 6
      months after AVR (Funada and Mizuno et al., Circ J 70:1312-7, 2006), and
      perioperative onset is very rare. Case presentation: An 80-year-old woman with
      severe aortic stenosis was scheduled to undergo AVR. AVR using cardiopulmonary
      bypass (CPB) was successfully carried out. However, 5 min following AVR, signs of
      left heart failure appeared, and transesophageal echocardiography (TEE) revealed
      severe hypokinetic left ventricular wall motion. Left coronary ostial stenosis
      was diagnosed by TEE, and CPB was immediately resumed and coronary artery bypass
      grafting (CABG) to the left anterior descending branch was performed.
      Conclusions: When circulatory failure presents in the acute phase following AVR,
      onset of coronary ostial stenosis should be considered.

PMID- 29457059
TI  - Unexpected bioprosthetic mitral valve thrombus during left ventricular assist
      device implantation.
AB  - Acute bioprosthetic valve thrombosis can occur after surgery and sometimes cause
      hemodynamic instability and cardiogenic shock. Risk factors for bioprosthetic
      valve thrombosis are hypercoagulability, atrial fibrillation, atrial dilatation,
      low cardiac function, and lack of anticoagulation therapy. The authors present a
      case of severe mitral stenosis due to bioprosthetic valve thrombus. The patient
      was diagnosed with dilated-phase hypertrophic cardiomyopathy and underwent mitral
      valve replacement. He required venoarterial extracorporeal membrane oxygenation
      (VA-ECMO) due to extremely low cardiac output and was scheduled for left
      ventricular assist device (LVAD) implantation. Transesophageal echocardiographic
      examination before LVAD implantation revealed severe mitral stenosis due to
      bioprosthetic mitral valve thrombus, which was not detected by transthoracic
      echocardiography in the intensive care unit and contributed to the low cardiac
      function. The thrombus was removed through an unscheduled left atriotomy before
      LVAD implantation. The possibility of bioprosthetic valve thrombosis must be
      considered when the patient is dependent on VA-ECMO support. Early
      transesophageal echocardiographic examination of the bioprosthetic valve may be
      helpful and contribute to surgical decision-making.

PMID- 29457060
TI  - Lower airway obstruction due to a massive clot resulting from late bleeding
      following mini-tracheostomy tube insertion and subsequent clot removal and re
      intubation.
AB  - Background: Easier to perform than the conventional procedure, mini-tracheostomy
      (MT) is widely used in the operating room or intensive care unit to remove sputum
      or other obstructions of the upper airway. This option, however, does carry the
      risk of various complications, including malposition, disposition, bleeding, and
      subcutaneous emphysema. Here, we report a case of endotracheal tube obstruction
      due to a massive clot resulting from late bleeding around the insertion site of
      an MT tube. This necessitated removal of the endotracheal tube together with the
      clot followed tube re-introduction. Case presentation: The patient was an 85-year
      old man in whom an MT tube had been inserted 6 days earlier following aortic
      replacement surgery. On re-admittance to our intensive care unit, large amounts
      of hemosputum and clotting were observed around the insertion site of the tube.
      The MT tube was subsequently removed and tracheal intubation performed.
      Ventilation via the endotracheal tube proved impossible, however, and cardiac
      arrest ensued. Fiberoptic bronchoscopy revealed that the endotracheal tube was
      completely obstructed by a massive clot. Therefore, we immediately pushed the
      clot toward the right main bronchus to secure ventilation via the left lung.
      After many attempts to remove the massive clot, including suction and grasping
      with basket forceps, it was successfully dislodged by replacing the endotracheal
      tube with a new one while maintaining oxygenation by one-lung ventilation. Any
      small fragments of the clot that still remained were then removed by suction
      under fiberoptic bronchoscopy. Conclusions: Here, we report a case of
      endotracheal tube obstruction due to a clot derived from very late (6 days)
      bleeding after insertion of an MT tube. The patient was successfully rescued by
      replacing the clot-bearing endotracheal tube with a new one. This experience
      suggests that the intensive care physician should be aware of the potential risk
      of clot retention in endotracheal tubes after the elapse of several days.

PMID- 29457061
TI  - Postoperative management with dexmedetomidine in a pregnant patient who underwent
      AVM nidus removal: a case report.
AB  - Background: Following cerebral arteriovenous malformation (AVM) surgery, severe
      brain edema and hemorrhage may be caused by postoperative normal perfusion
      pressure breakthrough (NPPB). Sedation is necessary for this population. It is a
      challenge for the anesthesiologist to maintain hemodynamic stability without
      interfering with the neurological assessment. In Japan, propofol is
      contraindicated for pregnant patients. Dexmedetomidine is a versatile drug in
      anesthesia practice and may be useful for this situation. There is no report
      using dexmedetomidine for the purpose of NPPB control in pregnant patients. We
      describe the postoperative management with dexmedetomidine for a pregnant patient
      who underwent cerebral AVM nidus removal. Case presentation: A 32-year-old
      patient presented with headache at the 16th week of gestation. Neuroimaging
      revealed an intraventricular hemorrhage and an AVM at the right anterior horn of
      the lateral ventricle which caused bleeding. A multidisciplinary team discussion
      was done, and then a craniotomy for AVM nidus removal was performed under general
      anesthesia. Preanesthetic aspiration prophylaxis and rapid sequence induction
      were added to our conventional anesthetic management. Hypotension occurred after
      anesthetic induction but the patient recovered by volume resuscitation and
      vasopressors. Anesthesia was maintained with 50% O2 in air and sevoflurane. The
      AVM was completely removed, and no perioperative complications occurred.
      Postoperative sedation with dexmedetomidine was used to prevent breakthrough
      hyperperfusion and cerebral edema. Conclusions: Dexmedetomidine infusion was used
      for postoperative sedation without causing any side effects, and it can be an
      alternative for sedation, especially when propofol is contraindicated.

PMID- 29457062
TI  - A case of left frontal high-grade glioma diagnosed during pregnancy.
AB  - Background: As pregnancy accelerates glioma growth, therapeutic abortion has been
      recommended prior to tumor resection. Additionally, it has also been suggested
      that the extent of glioma resection is closely correlated with patient survival.
      Case presentation: A 162-cm, 61.4-kg, 30-year-old, right-handed primigravida was
      referred to our institution at 21 weeks gestation to obtain a second opinion. At
      18 weeks gestation, the patient developed new-onset generalized convulsive
      seizures (GCSs), which were poorly controlled by anticonvulsant polytherapy,
      early in the second trimester. A 6-cm lesion located in her left frontal
      supplementary motor area (SMA) was suspected as a grade III glioma, classified
      according to the World Health Organization (WHO) guidelines. Due to the limited
      evidence on the use of adjuvant therapy during pregnancy, tumors causing
      neurological symptoms and seizures must be treated, in order to stabilize the
      maternal condition and enable a safe birth. In the case of pregnant patients,
      awake craniotomy using intraoperative magnetic resonance imaging (iMRI) is
      considered advantageous, achieving gross total resection with a reduction of
      direct cortical stimulation, which may induce seizure, and so reducing fetal
      exposure to anesthetics. The "Asleep-Awake-Asleep" technique was performed at 27
      weeks and 2 days gestation. As use of propofol in pregnant patients is
      prohibited, general anesthesia was maintained through administration of
      sevoflurane and remifentanil until the first scan of iMRI, and was subsequently
      re-induced with dexmedetomidine when tumor removal had been accomplished. A
      supraglottic airway (SGA) was used until the patient's cranium was opened. There
      were no complications during either the procedure or the post-operative period.
      At 35 weeks gestation, the patient delivered a healthy baby of 2317 g.
      Pathological examination of the patient, revealed an anaplastic astrocytoma, thus
      radiotherapy and chemotherapy began 2 months post-delivery. There is no evidence
      of tumor recurrence in the patient and the child did not show any medical or
      developmental concerns at the point of the 17-month follow-up. Conclusions: Since
      evidence on the use of adjuvant therapy during pregnancy is limited, extensive
      resection with functional monitoring is recommended if a brain tumor is presumed
      to be malignant. Awake craniotomy is considered advantageous to pregnant patients
      because subjective movement preserves the patient's motor function and reduces
      fetal exposure to anesthetics. Therefore, providing multidisciplinary discussion
      takes place within the decision-making process, as well as careful perioperative
      preparation, awake craniotomy should be considered, even in the case of pregnant
      patients.

PMID- 29457063
TI  - Monitoring of central venous pressure and stroke volume variation in a case with
      a ruptured brain arteriovenous malformation and Fontan circulation.
AB  - Background: Patients with complex congenital heart disease increasingly undergo
      noncardiac surgeries because of advancements in surgical techniques and medical
      management. In Fontan circulation, maintaining an adequate transpulmonary
      gradient is essential for preserving both pulmonary blood flow and cardiac
      output. However, intraoperative circulatory monitoring of Fontan patients has not
      been established. Case presentation: A 17-year-old girl required an emergency
      craniotomy for ruptured arteriovenous malformation. She had a surgical history of
      bidirectional Glenn operation and Fontan palliation for her congenital
      hypoplastic left heart syndrome and double outlet right ventricle. We performed
      general anesthesia with continuous monitoring of central venous pressure (CVP)
      and stroke volume variation (SVV). Transesophageal echocardiography was not
      conducted because of difficulty in manipulating the probe due to the patient's
      position and surgical setting. After incision of the dura, approximately 1700 ml
      of rapid blood loss from the arteriovenous malformation was observed in 30 min.
      In this period, CVP decreased from 15 to 5 mmHg or less. In contrast, there was
      only a slight rise in SVV from 5 to 8%. We rapidly administered fluid and then
      transfused blood, and CVP gradually recovered to 10-15 mmHg. During the surgery,
      circulatory collapse was not observed. The patient was transferred to the
      intensive care unit under sedation and controlled ventilation. Conclusions: CVP
      decreased sharply, whereas SVV rose only slightly during acute bleeding in the
      present case. CVP monitoring may have been useful for the management of an acute
      bleeding case with a Fontan circulation but SVV may not have been reliable. As
      more patients with a Fontan circulation undergo noncardiac surgeries, appropriate
      circulatory monitoring in these patients should be further investigated.

PMID- 29457064
TI  - A case of sudden onset of thyroid storm just before cesarean section manifesting
      congestive heart failure and pulmonary edema.
AB  - Background: Since acute respiratory failure (ARF) is a life-threatening
      complication, particularly in the gestational period, differential diagnosis and
      rapid treatment are required. Among the various causes of sudden onset of ARF,
      thyroid storm is a rare cause in a parturient complicated with well-controlled
      hyperthyroidism. In this case report, we describe a parturient with
      hyperthyroidism in whom a thyroid storm manifesting congestive heart failure and
      pulmonary edema developed just before an emergency ceasarean section, even though
      hyperthyroidism was well-controlled with antithyroid drugs. Case presentation: A
      36-year-old pregnant woman was diagnosed as having clinical chorioamnionitis, and
      an emergency cesarean section was performed at 25 weeks of pregnancy. She had a
      complication of hyperthyroidism accompanied by mild mitral regurgitation, and she
      had been treated with methimazole. She was treated with ritodrine and MgSO4 for
      the threat of premature delivery. At the preoperative consultation, her
      percutaneous oxygen saturation (SpO2) was 98% on room air. When she was admitted
      to the operating room, her heart rate and blood pressure were 130 beats/min and
      196/78 mmHg, respectively. SpO2 was 88% on room air without any symptoms;
      however, just after starting oxygen administration via a facemask, she complained
      of severe respiratory distress and became agitated. Partial pressure of arterial
      oxygen was 108 mmHg with an inspiratory oxygen fraction of 1.0. Chest radiography
      revealed pulmonary congestion, and transesophageal echocardiography revealed
      normal right ventricular function without an embolus and severe mitral
      regurgitation with preserved left ventricular function. Contrast-enhanced
      computed tomography after the operation revealed no pulmonary embolus but
      revealed a pulmonary effusion, and free triiodothyronine level was increased at
      the onset of dyspnea. Therefore, we diagnosed the causes of sudden onset of
      dyspnea as pulmonary edema and congestive heart failure induced by a thyroid
      storm. Conclusion: Sudden onset of a thyroid storm just before a cesarean section
      occurred in a patient with several risk factors of thyroid storm and pulmonary
      edema, including pregnancy, treatment with tocolytic agents, and infection. The
      involvement of these multiple factors was considered to be the cause of the
      sudden onset of the thyroid storm and the cause of rapidly progressive pulmonary
      edema.

PMID- 29457065
TI  - A devised strategy for tracheal extubation for predicted difficult airway in a
      child with unilateral vocal cord paralysis: a case report.
AB  - Background: Extubation is a more challenging medical practice than intubation,
      and countermeasures against it are similar to those described in the Difficult
      Intubation Guidelines, but problems cannot be overcome by completely the same
      methods. We predicted difficult extubation in a pediatric patient with left
      recurrent laryngeal nerve paralysis and devised an extubation method. Case
      presentation: The patient was a 2-year-and-8-month-old boy scheduled for cleft
      palate repair. Concomitant cardiac anomaly and first and second branchial arch
      syndrome-associated facial malformations, such as mandibular micrognathia and
      auricular malformation, were observed. He had a past medical history of difficult
      intubation and respiratory arrest on a catheter test under intravenous sedation
      at 4 months old. Left recurrent laryngeal nerve paralysis was discovered on
      preoperative examination of the cleft palate, based on which difficulty in
      postoperative extubation was predicted. A catheter for tracheal tube exchange
      proposed by the extubation guidelines of the Difficult Airway Society (DAS) was
      placed, endoscopic examination was performed while inducing spontaneous breathing
      and swallowing reflex by an otolaryngologist, and the tube was removed while
      movement of the tissue around the glottis was visually evaluated. The patient was
      managed in an ICU after extubation, and both the systemic and respiratory
      conditions were favorable. Conclusions: Extubation and airway management could be
      safely performed by devising extubation while conforming to the DAS guidelines.

PMID- 29457066
TI  - Dexmedetomidine-treated hyperventilation syndrome triggered by the distress
      related with a urinary catheter after general anesthesia: a case report.
AB  - Background: Hyperventilation syndrome (HVS) sometimes occurs in patients under
      stressful conditions and may provoke severe complications such as myocardial
      infarction and death. The authors report a case of HVS following general
      anesthesia, where a continuous intravenous infusion of dexmedetomidine was
      effective for HVS. Case presentation: A 23-year-old male patient with recurrent
      tongue cancer was scheduled to undergo partial glossectomy and neck dissection.
      Emergence from general anesthesia was prompt. Twenty-two minutes after
      extubation, the patient complained of unbearable distress caused by the urinary
      catheter. He began to cry, with an increased respiratory rate of over 40 breaths
      per minute. Intravenous infusion of flurbiprofen, droperidol, and morphine was
      not effective. Electrocardiography and laryngofiberscopy indicated the absence of
      acute coronary syndrome and airway obstruction, respectively. An arterial blood
      gas determination showed pH 7.63, PaCO2 18.2 mmHg, PaO2 143 mmHg on O2 mask 4
      L/min, Ca2+ 4.29 mmol/L, and lactate 3.4 mmol/L. The patient was diagnosed with
      HVS. Dexmedetomidine infusion 2.0 MUg/kg/h for 10 min followed by 0.7 MUg/kg/h
      reduced respiratory rate, suppressed arousal, and disappeared the complaint of
      bladder distension. One hour after extubation, an arterial blood gas
      determination showed pH 7.33, PaCO2 51.3 mmHg, PaO2 196 mmHg on O2 mask 4 L/min,
      Ca2+ 4.70 mmol/L, and lactate 1.5 mmol/L. After admission to the intensive care
      unit, dexmedetomidine infusion was maintained at the rate of 0.2 to 0.7 MUg/kg/h
      until the following morning, and he did not complain of distress caused by the
      urinary catheter. Conclusions: HVS can occur after emergence from general
      anesthesia, and dexmedetomidine infusion was effective for HVS.

PMID- 29457067
TI  - An educational program for decreasing catheter-related bloodstream infections in
      intensive care units: a pre- and post-intervention observational study.
AB  - Background: Central venous catheters (CVCs) are commonly used in the management
      of critically ill patients. This study aimed to determine whether an educational
      program could reduce the rate of catheter-related bloodstream infections (CRBSIs)
      in intensive care units (ICUs). Findings: All patients admitted to a medical ICU
      at a college affiliated with the Japan Society of Intensive Care Medicine between
      January 2008 and December 2014 were surveyed prospectively for the development of
      CRBSIs. A mandatory educational program (the intervention) targeting an infection
      control committee consisting of physicians was developed by a multidisciplinary
      task force to highlight correct practices for preventing CRBSIs. The program
      included a 30-min video-based introduction, 120-min lectures with a number of
      hands-on training sessions, a post-test, posters, safety check sheets, and
      feedback from the infection control committee. Lectures based on the education
      program were held every 3 months, and participants were free to choose when they
      attended the lectures. Each participant was required to view the 30-min
      introduction before attending the 120-min lectures and complete the post-test
      after each lecture. Safety check sheets were made to ascertain adherence to
      contents of the educational program. Posters describing the educational program
      were posted throughout the ICU. A pre- and post-intervention observational study
      design was employed, with the main outcome measure being yearly CRBSIs. We also
      calculated cost savings that resulted from improved CRBSI rates.During the 12
      month pre-intervention period, four episodes of CRBSIs occurred in 1171 patient
      ICU-days (i.e., 3.4 per 1000 patient ICU-days). In the first year after the
      intervention, the rate of CRBSIs decreased to 0 in 1157 patient ICU-days (P <=
      0.05). The estimated cost savings secondary to this decreased rate for the 1 year
      following introduction of the program was between 1850,000 and 27,000,000 yen
      ($14,800-$216,000). Conclusions: A program aimed at educating healthcare
      providers on the prevention of CRBSIs led to a dramatic decrease in the rate of
      primary bloodstream infections. This suggests that educational programs may
      substantially decrease medical care costs and patient morbidity attributed to
      central venous catheterization when implemented as part of mandatory training.

PMID- 29457068
TI  - Abdominal compartment syndrome during hip arthroscopy for an acetabular fracture:
      a case report.
AB  - Background: We encountered a case of abdominal compartment syndrome during hip
      arthroscopic surgery, caused by the irrigation fluid flowing into the peritoneal
      cavity. Case presentation: A 47-year-old male patient with the acetabulum
      fracture underwent open reduction and internal fixation with hip arthroscopy.
      Hypothermia, increased airway pressure (under volume-controlled ventilation) and
      oliguria were observed during the operation, and arterial blood gas analysis
      showed decreased oxygenation and metabolic acidosis. Abdominal distention was
      observed, and a postoperative CT revealed accumulation of a large volume of
      irrigation fluid in the peritoneal cavity and retroperitoneum. The patient was
      diagnosed as having abdominal compartment syndrome and treated by percutaneous
      peritoneal drainage. His subsequent course was uneventful, and he was discharged
      8 weeks after the operation. Intraperitoneal extravasation of irrigation fluid
      may occur during hip arthroscopic surgery, and is more likely to occur in the
      presence of an injury. Conclusion: Anesthesiologists should be aware of the
      possible occurrence of the abdominal compartment syndrome during hip arthroscopic
      surgery and ensure that it is detected early.

PMID- 29457069
TI  - Bacillus cereus pneumonia in an immunocompetent patient: a case report.
AB  - Background: Bacillus cereus (B. cereus) rarely causes lower respiratory tract
      infections, although most reported cases of B. cereus pneumonia are fatal despite
      intensive antibiotic therapy. We present a case of B. cereus pneumonia in an
      immunocompetent patient. Case presentation: An 81-year-old woman was transferred
      from a district general hospital to our hospital for treatment of congestive
      heart failure. The patient presented with a nonproductive cough, dyspnea, edema
      in both lower extremities, orthopnea, fever, and occult blood in the stool. A
      chest radiograph indicated bilateral pleural effusion and pulmonary congestion.
      After diuretic therapy and chest drainage, bilateral pleural effusion and
      pulmonary congestion improved. On day 2, she experienced severe respiratory
      distress. B. cereus was isolated from two blood sample cultures. On day 4, her
      condition had progressed to severe respiratory distress (PaO2/FiO2 ratio = 108).
      A chest radiograph and computed tomography indicated extensive bilateral
      infiltrates. She was transferred to the intensive care unit and was intubated. B.
      cereus was also isolated from five blood sample cultures at that time. After
      isolating B. cereus, we switched antibiotics to a combination of imipenem and
      levofloxacin, which were effective. She had no history of immunodeficiency,
      surgery, ill close contacts, risk factors for HIV or tuberculosis, recent central
      venous catheter insertion, or anthrax vaccination. She improved and was
      discharged from the intensive care unit after several days. Conclusion: This is a
      rare case of B. cereus pneumonia in an immunocompetent patient, who subsequently
      recovered. Bacillus should be considered as a potential pathogen when
      immunocompetent patients develop severe pneumonia.

PMID- 29457070
TI  - Sudden onset of artery dissection in a 32-year-old woman with vascular Ehlers
      Danlos syndrome due to psychological stress of her mother's death: a case series.
AB  - Background: Patients with vascular Ehlers-Danlos syndrome (EDS) are susceptible
      to significant vascular complications, such as aortic and visceral arterial
      ruptures, aneurysms, and dissection. We describe a case of repeated bleeding in a
      57-year-old woman and a case of sudden onset of artery dissection in her
      daughter, both of whom were previously diagnosed with vascular EDS and managed at
      our institution. Case presentation: A 57-year-old woman was admitted to our
      emergency department due to sudden onset of left low back pain. Her past history
      included vascular EDS. An urgent abdominal computed tomography (CT) scan revealed
      a left-sided retroperitoneal hematoma and left external iliac artery dissection.
      Stent graft repair was performed. Five hours postoperatively, cardiac arrest
      occurred and resuscitation attempts failed. The 32-year-old daughter with
      genetically diagnosed vascular EDS was notified of the death of her mother during
      the customary end-of-life conference. Six hours after her mother's death, she was
      admitted to our emergency department due to sudden onset of left low back pain.
      On examination, she was not in hypovolemic shock, and weak pulses were palpable
      in the bilateral dorsalis pedis. An urgent abdominal CT scan revealed a right
      sided retroperitoneal hematoma around the right external iliac artery and left
      external iliac artery dissection. She was admitted to the intensive care unit and
      underwent conservative therapy consisting of bed rest and antihypertensive
      therapy with nicardipine. She developed no further vascular complications
      requiring surgical intervention and was discharged on the 21st hospital day.
      Conclusions: Vascular rupture can be fatal in patients with vascular EDS. This
      report underscores the importance of strategic management of vascular
      complications to prevent rupture, and the importance of psychological care for
      the bereaved family given the hereditary nature of vascular EDS.

PMID- 29457071
TI  - General anesthesia in a patient with asymptomatic second-degree two-to-one
      atrioventricular block.
AB  - Background: The major perioperative concern in patients with second-degree
      atrioventricular (AV) block is the progression to complete AV block. Therefore,
      the prophylactic implantation of a temporary pacemaker prior to surgery is
      recommended, especially in symptomatic patients. However, as no quantitative
      preoperative risk assessment from progression to complete AV block is available,
      there is currently no established indication for preoperative prophylactic
      pacemaker implantation. Here, we present a case of progression from asymptomatic
      second-degree two-to-one (2:1) AV block to complete AV block following the
      induction of general anesthesia. Case presentation: A 69-year-old female with
      degenerative spinal stenosis was scheduled for transforaminal lumbar interbody
      fusion surgery under general anesthesia. She had no cardiac symptoms, but routine
      preoperative resting 12-lead electrocardiogram revealed second-degree 2:1 AV
      block. After discussion with the surgeon and referring cardiologist, we scheduled
      the surgery without implantation of a temporary pacemaker before surgery for the
      following reasons: (1) asymptomatic, (2) no evidence of underlying cardiac
      disease, and (3) a narrow QRS complex. On the day of surgery, general anesthesia
      was induced with 150 mg of intravenous thiamylal and 25 MUg of fentanyl, followed
      by intravenous administration of 50 mg of rocuronium to facilitate endotracheal
      intubation. Sevoflurane (1.0-2.0%) was used to maintain anesthesia. A few minutes
      after induction, the 2:1 AV block progressively converted to complete AV block,
      and the surgery was postponed. During emergence from anesthesia, the third-degree
      AV block recovered to 2:1 AV block, similar with the preoperative pattern. The
      patient was monitored in the intensive care unit for 2 days and then transferred
      to the normal orthopedic ward uneventfully. One month later, the surgery was
      rescheduled with preoperative implantation of a temporary pacemaker. A slow mask
      induction using sevoflurane with oxygen was started. Upon loss of consciousness
      during the inhalation of initial sevoflurane, complete AV block developed and
      temporary pacing was immediately initiated. Subsequent anesthesia and surgery
      were uneventful. The patient made an uncomplicated recovery from surgery with
      stable hemodynamics. The temporary pacemaker was not required after surgery, and
      the pacemaker catheter was removed 1 day after surgery. Conclusions: The present
      case indicates that a prophylactic pacemaker should be implanted preoperatively
      in patients who have 2:1 AV block even without symptoms.

PMID- 29457072
TI  - Anesthetic management of cesarean section in a patient with a large anterior
      mediastinal mass: a case report.
AB  - Background: Symptomatic anterior mediastinal mass in pregnancy is rare, and
      cesarean section for such patients poses a risk of cardiopulmonary collapse. Case
      presentation: A 30-year-old woman at 40 weeks' gestation complained of
      breathlessness and cough, and she was not able to lie supine because of
      respiratory distress. Computed tomography scan revealed a large anterior-superior
      mediastinal mass severely compressing the trachea, bilateral main bronchus, and
      superior vena cava. Because clinical symptoms and computed tomographic findings
      suggested imminent respiratory catastrophe, urgent cesarean section was planned.
      The patient was able to lie in the semi-recumbent position with minimal symptoms;
      therefore, we considered it safe to perform cesarean section with combined spinal
      epidural anesthesia. In the event of cardiopulmonary collapse, emergent
      intubation and extracorporeal membrane oxygenation were also planned. The
      operation was performed successfully with combined spinal epidural anesthesia.
      The infant was healthy, and the postoperative hospital course was uneventful.
      Conclusions: Combined spinal epidural anesthesia is preferable in the anesthetic
      management of cesarean section with symptomatic anterior mediastinal mass. A well
      designed preoperative strategy can lead to favorable outcomes even in this
      complicated situation.

PMID- 29457073
TI  - Sevoflurane prolonged the QTc interval and increased transmural dispersion of
      repolarization in a patient with long QT syndrome 3: a case report.
AB  - We report that sevoflurane not only caused marked QTc interval prolongation but
      also increased transmural dispersion of repolarization in a patient with long QT
      syndrome 3 (LQT3). A 16-year-old male with LQT3 underwent a shoulder operation.
      He experienced no episode of syncope or cardiac arrest, but his preoperative
      electrocardiography (ECG) showed marked QTc interval prolongation (631 ms) and Tp
      e interval prolongation (126 ms). Anesthesia was induced with propofol and
      maintained with 2% sevoflurane and remifentanil. Although no lethal arrhythmias
      occurred in the perioperative period, not only the QTc interval but also Tp-e
      interval was further prolonged by sevoflurane. While sevoflurane has been
      recognized as a safe anesthetic in terms of QT interval prolongation, even in
      patients with long QT syndromes, we believe that sevoflurane might be avoided for
      poorly controlled LQT3 patients.

PMID- 29457074
TI  - Effect of different surgical procedures on the accuracy of prediction of the
      plasma concentration of fentanyl: comparison between mastectomy and laparoscopic
      prostatectomy.
AB  - Background: The accuracy of simulation-predicted fentanyl concentration in
      different types of surgical procedure is not fully understood. We wished to
      estimate the effect of different types of surgical procedure on the accuracy of
      such simulations. Findings: Fifty patients who had undergone elective mastectomy
      or laparoscopic prostatectomy (American Society of Anesthesiologists physical
      status = I-II) were enrolled. Anesthesia was maintained throughout surgery with
      sevoflurane and a bolus infusion of fentanyl. A maintenance infusion was
      administered with 8 mL/kg/h Ringer's acetate solution from the start of
      anesthesia to completion of blood sampling. An infusion to compensate for blood
      loss was administered (one to two volumes of hydroxyethyl starch). A blood sample
      was drawn every 30 min during anesthesia.We measured the plasma concentration of
      fentanyl in 358 samples from 50 patients. The plasma concentration of fentanyl
      was correlated significantly with the simulated predicted fentanyl concentration
      (r = 0.734, P < 0.01) but 36.0% of all samples had a difference greater than +/
      0.5 ng/mL. Approximately 0.3 ng/mL of a fixed bias was shown throughout
      mastectomy. During laparoscopic prostatectomy, the fixed bias gradually became
      negative from ~0.3 to -0.3 ng/mL as the sampling stage proceeded. Conclusions:
      The predicted concentration of fentanyl was significantly correlated with the
      plasma concentration of fentanyl (r = 0.734). However, there were different
      patterns of a fixed bias between mastectomy and laparoscopic prostatectomy
      groups. We should pay attention to this tendency among different surgical
      procedures. Trial registration: UMIN000005110.

PMID- 29457075
TI  - A case of unexpected impaired oxygenation due to intraoperative pneumothorax: an
      adverse event associated with respiratory management with spontaneous respiration
      in a patient with esophagobronchial fistulae.
AB  - Background: Respiratory management in patients with esophagobronchial fistulae is
      challenging since positive pressure ventilation (PPV) may not be feasible due to
      air leaks and possible risks for regurgitation and aspiration of gastric
      contents. We and others have previously reported that spontaneous respiration may
      be one of the good options of respiratory management during general anesthesia in
      those patients. However, adverse events associated with this respiratory strategy
      have not been reported previously. We experienced a 77-year-old male patient who
      suffered unexpected impairment of oxygenation due to intraoperative pneumothorax,
      which was assumed to have been exacerbated by spontaneous respiration during
      esophageal bypass surgery. Case presentation: The patient was planned to undergo
      esophageal bypass surgery for esophagobronchial fistulae associated with
      malignant esophageal cancer. Both of two esophagobronchial fistulae were located
      in the proximal part of the left main bronchus. For the risks of air leaks and
      aspiration associated with PPV and further damage to the tissue around the
      fistulae, we decided to maintain spontaneous respiration under general anesthesia
      and obtain abdominal muscle relaxation with epidural anesthesia. After
      catheterization of epidural anesthesia, the patient was sedated with 35 mg of
      intravenous pethidine and was nasotracheally intubated under bronchoscopic
      guidance. We confirmed that the tip of the tracheal tube was located above the
      carina. Then anesthesia was induced and maintained with sevoflurane so that his
      spontaneous respiration could be maintained thereafter. His spontaneous
      respiration was assisted with 3 cmH2O of pressure support. Approximately 60 min
      into the surgery, percutaneous arterial oxygen saturation (SpO2) suddenly dropped
      from 99 to 89% with an inspiratory fraction of oxygen of 0.4. We assumed that
      lung atelectasis associated with airway secretion or pulmonary soiling was the
      most likely reason for impaired oxygenation; however, arterial oxygenation only
      partially regained even after they were suctioned. After the completion of the
      surgery, chest X-ray revealed right pneumothorax. After a chest drainage tube was
      inserted, right pneumothorax was ameliorated and SpO2 returned to the baseline
      level. Conclusions: Although spontaneous respiration may be useful in a patient
      with esophagobronchial fistulae, oxygenation can be impaired more seriously than
      PPV in case intraoperative pneumothorax occurs.

PMID- 29457076
TI  - Schwartz-Jampel syndrome is not related to malignant hyperthermia.
AB  - Schwartz-Jampel syndrome (SJS) is a rare syndrome that is clinically
      characterized by myotonia and skeletal abnormalities. Most reports regarding SJS
      have stated that patients with SJS are susceptible to malignant hyperthermia
      (MH). The statement is incorrect. There is no report showing that SJS is related
      to MH. Scientific evidence also shows that patients with myotonias are not
      susceptible to MH except for that with hypokalemic periodic paralysis. Medical
      practitioners must recognize that SJS is not related to MH.

PMID- 29457077
TI  - Ultrasound-guided para-umbilical block: a pediatric case.
AB  - Background: Rectus sheath block is a common peripheral nerve block for patients
      undergoing umbilical hernia repair surgery. However, rectus sheath block alone
      can affect only anterior branches of intercostal nerves and, therefore, is
      incomplete for postoperative analgesia for the anterior abdomen, which is
      innervated by both anterior and lateral branches. We describe a successful
      perioperative analgesia with ultrasound-guided para-umbilical block after
      pediatric umbilical hernia surgery. Case presentation: A 4-year-old child
      underwent hernia repair surgery. Following induction of general anesthesia, the
      anatomy of the umbilical region was observed under ultrasound with a 5-10-MHz
      linear probe. An ultrasound-guided injection between the rectus abdominis muscle
      and the posterior lobe of the rectus sheath and an injection into the
      subcutaneous space around the umbilicus were performed. The peripheral nerve
      block was effective during surgery, and the patient required no additional rescue
      analgesia during the perioperative period. There were no complications.
      Conclusion: We performed ultrasound-guided para-umbilical block with four
      injections. This peripheral nerve block could be an efficient technique for
      complete perioperative analgesia.

PMID- 29457078
TI  - Endovascular repair with extracorporeal membrane oxygenation as a rescue strategy
      for aortobronchial fistula: a case report.
AB  - Aortobronchial fistula (ABF) is a rare and potentially lethal complication of
      thoracic aortic replacement surgery. Currently, thoracic endovascular aortic
      repair (TEVAR) has emerged as a less invasive alternative to open surgery for ABF
      to facilitate prompt hemostasis. However, there are no published reports of TEVAR
      for ABF, particularly for presentation with life-threatening respiratory failure
      from massive hemoptysis. A 48-year-old male patient, who had recently undergone
      aortic root and arch replacement due to aortic dissection, was transferred to the
      emergency department with massive hemoptysis and severe dyspnea. A single-lumen
      endotracheal tube was immediately placed in the right main bronchus to protect
      the nonbleeding lung from spillage of blood. Chest computed tomography (CT)
      showed leakage of contrast material from the distal anastomosis of the aortic
      graft and consolidated lung tissue adjacent to the leakage. He was diagnosed with
      an ABF following aortic arch replacement, and an emergency TEVAR was performed.
      After adequate hemostasis, severe hypercapnia remained uncorrected despite the
      maximum ventilatory support. Thus, venovenous extracorporeal membrane oxygenation
      (VV ECMO) was immediately initiated, and severe respiratory acidosis improved
      dramatically. Furthermore, VV ECMO facilitated prompt bronchoscopic washout of
      the remaining blood clot without any danger of respiratory collapse and was
      weaned off successfully after 5 days as ventilation improved. This case
      demonstrates that emergency TEVAR in combination with VV ECMO can be a rescue
      strategy for massive hemoptysis from an ABF.

PMID- 29457079
TI  - A case of a warfarinized renal cancer patient monitored for prothrombin time
      international normalized ratio during methadone introduction.
AB  - Background: Warfarin, a widely used anticoagulant, interacts with various agents
      used in palliative care, such as oxycodone, morphine, acetaminophen, and non
      steroidal anti-inflammatory drugs (NSAIDs); however, there are no reports of its
      interaction with methadone. We report a case of a patient receiving warfarin when
      methadone was introduced for pain control with monitoring of the prothrombin time
      international normalized ratio (PT-INR) and deduced the pharmacological
      background. Case presentation: A 60-year-old male was emergently admitted to our
      university hospital for the sudden onset of severe back pain. Abdominal CT
      imaging revealed that the vertebral body of the ninth thoracic vertebra was
      occupied by bone metastasis and crushed, which caused his back pain. He received
      warfarin 3.5 mg/day for atrial fibrillation and tapentadol 100 mg p.o. daily for
      pain relief. The prothrombin time-international normalized ratio (PT-INR) was
      maintained at >2.2. The patient's history included diabetes mellitus and
      hypertension, but his laboratory test was unremarkable with the exception that
      his eGFR was 34 ml/min.Initially, a fentanyl dermal patch was used instead of
      tapentadol to avoid interactions with warfarin. We started concomitant
      administration of oxycodone and 2.4 g/day of acetaminophen while monitoring the
      PT-INR because acetaminophen increased the PT-INR to 2.93. A continuous
      intravenous infusion of oxycodone was introduced, in increments of the dose,
      resulting in an increase of the PT-INR to 3.41, which is required to reduce the
      dose of warfarin to 1.5 mg. Because of the lack of effective pain relief,
      methadone was introduced and the dose was gradually increased. The PT-INR was not
      changed and the dose of warfarin was not changed. An infusion of oxycodone and
      oral methadone was used to allow the patient to walk in his room, and he was
      later transferred to the palliative hospital. Conclusions: In an oral
      warfarinized patient, methadone seemed to undergo different metabolism than
      oxycodone. When warfarin and methadone are used together, we have to consider
      their interaction by comparing the competitive inhibition of CYP2C9 to the
      induction of CYP3A4 by methadone, because CYP3A4 metabolize various drugs
      including oxycodone.

PMID- 29457080
TI  - Desflurane anesthesia worsens emergence agitation in adult patients undergoing
      thyroid surgery compared to sevoflurane anesthesia.
AB  - Background: The effect of volatile anesthetics on emergence agitation in adults
      remains unclear. We compared the degree of emergence agitation between desflurane
      and sevoflurane anesthesia in adults undergoing thyroid surgery. Findings: One
      hundred and sixteen patients with American Society of Anesthesiologists status 1
      or 2 were randomized into two groups: the desflurane group (group D) and the
      sevoflurane group (group S). After induction of anesthesia with fentanyl (1-2
      MUg/kg) and propofol (1.5-2.5 mg/kg), tracheal intubation was facilitated with
      suxamethonium (0.5-1.0 mg/kg). In group D, anesthesia was maintained with
      desflurane in 66% nitrous oxide and 33% oxygen supplemented with fentanyl when
      necessary; in group S, sevoflurane was used instead of desflurane. After the end
      of the surgery, emergence agitation was evaluated with a modified pediatric
      anesthesia emergence delirium scale (ranging from 0 to 16, with higher scores
      indicating more severe emergence agitation) before extubation. Time to extubation
      from the end of the surgery, postoperative pain (evaluated by a numerical rating
      scale [NRS]), and postoperative nausea and vomiting (PONV) after surgery were
      examined. The degree of emergence agitation was more severe in group D than in
      group S (median [interquartile range]: 5 [4-7] vs 4 [2-6], p = 0.008). Time to
      extubation, NRS scores, and PONV rates were similar between the two groups.
      Conclusions: Desflurane anesthesia worsened emergence agitation as compared with
      sevoflurane in adult patients undergoing thyroid surgery, but did not affect time
      to extubation, postoperative pain, or PONV. Trial registration: UMIN000014215.

PMID- 29457081
TI  - Anesthetic management of a patient with narcolepsy by combination of total
      intravenous and regional anesthesia: a case report.
AB  - Narcolepsy is a neurological disease characterized by excessive daytime
      sleepiness, cataplexy, and/or a sudden loss of muscle tone due to malfunction of
      the orexinergic system, which may cause delayed emergence from general
      anesthesia. We report a successful anesthetic management of 24-year-old female
      narcoleptic patient undergoing left anterior cruciate ligament reconstruction.
      Anesthesia was induced and maintained with total intravenous anesthesia (TIVA)
      using propofol and remifentanil. Ultrasound-guided left femoral nerve block was
      also performed with 0.375% ropivacaine 20 ml. Acetaminophen 1000 mg was
      intravenously administered as part of a multimodal analgesia. After the surgery,
      the trachea was extubated 9 min after termination of TIVA, and then, the patient
      correctly responded to verbal commands. The postoperative course was uneventful
      without any narcoleptic symptoms.

PMID- 29457082
TI  - Factors affecting extubation time following pediatric ambulatory surgery: an
      analysis using electronic anesthesia records from an academic university
      hospital.
AB  - Background: In pediatric general anesthesia, our goal should be quicker
      extubation to facilitate rapid turnover in the operating room without
      compromising on safety and quality of anesthesia. Although many studies have
      focused on improving safety and pursuing a higher quality of recovery, factors
      related to anesthesia emergence remain unclear. We must, therefore, identify
      factors that influence the process of emergence from general anesthesia in
      children. Findings: We retrospectively examined 148 children (aged 1-6 years,
      American Society of Anesthesiologists physical status: 1-2) who had undergone <2
      h of ambulatory surgery. Clinical measures included time from the end of surgery
      to extubation (extubation time), age, height, weight, surgical time, mean
      indirect blood pressure during surgery, mean heart rate during surgery, mean end
      tidal carbon dioxide during surgery (mETCO2), mean body temperature during
      surgery (mBT), and total amount of fentanyl. Anesthetic procedures involved
      sevoflurane or propofol. Multiple regression analysis revealed that mETCO2 (p <
      0.01) and mBT (p < 0.01) were independent clinical factors associated with
      extubation time following pediatric ambulatory surgery. Conclusions: This study
      of 148 pediatric patients demonstrated that anesthesia emergence may be
      associated with mBT and mETCO2 following pediatric ambulatory surgery. These
      results show that perioperative vital signs are important in the prevention of
      delayed emergence for pediatric patients.

PMID- 29457083
TI  - Risk factors for rescue analgesic use on the first postoperative day after upper
      limb surgery performed under single-injection brachial plexus block: a
      retrospective study of 930 cases.
AB  - Background: Postoperative pain management after upper limb surgery is important
      for preventing adverse events that can prolong hospital stay and cause
      readmission. This study aimed to identify the risk factors associated with rescue
      analgesic use on the first postoperative day after upper limb surgery performed
      under single-injection brachial plexus block (BPB). Findings: We retrospectively
      analyzed records from 930 patients who underwent upper limb surgery under a
      single-injection BPB. Postoperatively, patients were administered oral loxoprofen
      regularly and rescue analgesics when analgesia was insufficient. We assessed the
      association between patient, surgical information, and rescue analgesic use on
      the first day after surgery (from 7:00 PM on the day of surgery to 7:00 AM on the
      first postoperative day), using a logistic regression model. Multivariate
      analysis revealed a significant association between rescue analgesic use and bone
      surgery, in particular, osteotomy, ligament repair and reconstruction,
      osteosynthesis, treatment for an amputated digit, and surgical duration.
      Conclusion: Bone surgery (osteotomy, ligament repair and reconstruction,
      osteosynthesis, treatment for an amputated digit) and a longer operative time
      were risk factors for rescue analgesic use for treating postoperative pain after
      upper limb surgery performed under single-injection BPB.

PMID- 29457084
TI  - Right ventricular functional assessment by three-dimensional transesophageal
      echocardiography is useful for withdrawal from a right ventricular assist device:
      a case report.
AB  - Right ventricular assist device (RVAD) implantation is one type of surgical
      treatment used for right heart failure. It is important to assess right
      ventricular (RV) function precisely when RVAD withdrawal is considered. Although
      assessment of RV function is difficult due to its complicated shape and
      contraction pattern, the volumetric analysis method of three-dimensional (3D)
      transesophageal echocardiography (TEE) has been developed and is useful for this
      task. We report the case of a 79-year-old man who successfully underwent RVAD
      withdrawal and evaluation using 3D TEE. 3D TEE had an important role in
      determining the timing of withdrawal from RVAD in this case.

PMID- 29457085
TI  - A case in which a capnometer was useful for diagnosing laryngospasm following
      administration of sugammadex.
AB  - Background: Sugammadex has been reported to cause upper-airway obstruction, such
      as laryngospasm or bronchospasm. These two conditions are treated using different
      approaches, but the differential diagnosis is difficult. Case presentation: We
      describe a case in which general anesthesia was administered via endotracheal
      intubation, in combination with brachial-plexus block, for arthroscopic surgical
      treatment of a rotator-cuff tear caused by recurrent shoulder dislocation. The
      total dose of rocuronium administered was 90 mg, and the last dose of 10 mg was
      given 15 min before the end of the surgery. Sugammadex was intravenously
      administered at 100 mg to reverse the effect of rocuronium after the operation
      ended. After extubation in this case, we placed a mask firmly around the
      patient's mouth, and thus, there was no air leakage around the mask. We detected
      upper-airway obstruction that was presumably attributable to administration of
      sugammadex. The end-tidal carbon dioxide (EtCO2) concentration was undetectable
      on a capnometer. Although 100% oxygen was administered at 10 L/min via a
      facemask, oxygen saturation (SpO2) decreased to approximately 70%. With suspected
      onset of laryngospasm, continuous positive airway pressure with 100% oxygen at 10
      L/min was started at 30 cm H2O. The patient's airway obstruction resolved after a
      short time. Conclusion: The use of a capnometer facilitated the diagnosis of
      laryngospasm and allowed us to administer appropriate treatment after
      administration of sugammadex.

PMID- 29457086
TI  - Spinal cord infarction following epidural and general anesthesia: a case report.
AB  - Background: Epidural anesthesia is widely used for postoperative analgesia and
      rarely causes permanent neurological complications. We report a case of
      paraplegia following abdominal surgery under combined epidural/general
      anesthesia. Case presentation: A 75-year-old woman underwent a scheduled
      abdominal total hysterectomy and bilateral salpingo-oophorectomy for suspected
      endometrial cancer. In the operating room, an epidural catheter was inserted at
      T11/12 while the patient was conscious. The needle entered smoothly, with no
      observed bleeding, paresthesia, or pain, and general anesthesia was induced.
      During surgery, 4 mL of 0.25% levobupivacaine and 0.1 mg of fentanyl were
      administered via the epidural catheter, and a solution of 2.5 MUg/mL fentanyl and
      0.2% levobupivacaine was continuously infused at 4 mL/h for postoperative
      analgesia. The patient promptly regained consciousness and could move her
      bilateral lower extremities without difficulty upon leaving the operating room.
      During the first postoperative night, she complained of an absence of sensation
      and weakness in the lower extremities. By the morning of the second postoperative
      day, she had developed paralysis and sensory losses associated with touch,
      temperature, pinprick, and vibration below T5. The epidural infusion was stopped.
      Magnetic resonance imaging (MRI) revealed a hyperintense area of the thoracic
      cord from T8 to T11, and spinal cord infarction was suspected. Ossification of
      the yellow spinal ligaments between T11 and T12, resulting in thoracic canal
      stenosis and thoracic spinal cord compression, were observed. Notably, the
      epidural catheter was inserted at the same site where the thoracic canal stenosis
      was present. Conclusions: Permanent neurological complications of epidural
      anesthesia are rare. Studies of neurological complications after epidural/spinal
      anesthesia have noted the possibility of spinal anomalies, such as lumbar
      stenosis, in relation to neurological complications after epidural/spinal
      anesthesia. In this case, the onset of spinal cord infarction may have occurred
      coincidentally with catheter insertion into the site of existing spinal stenosis.
      Therefore, it is important to evaluate lower extremity symptoms and consider
      spinal disease before administering epidural anesthesia. Spinal cord infarction
      may be prevented by preoperatively identifying spinal lesions using computed
      tomography or MRI in cases of suspected spinal disease.

PMID- 29457087
TI  - Remifentanil for sedation and analgesia during awake division of tongue flap in
      children: a report of two cases.
AB  - Background: The tongue flap is an accepted treatment method for cleft palate
      repair. Orotracheal or nasotracheal intubation using a fiberoptic scope is
      preferred for the division of the tongue flap. We report two cases of tongue flap
      division in which the patients received adequate sedation and analgesia without
      tracheal intubation. Case presentation: Twelve- and 13-year-old male patients
      were treated at our hospital for tongue flap division, performed as part of a
      cleft palate repair. We planned to divide the tongue flap under sedation with
      remifentanil (1 MUg/kg/min continuous infusion) and local anesthesia, followed by
      induction of general anesthesia, and orotracheal intubation after the tongue flap
      was divided. During the procedure, patients were breathing spontaneously and were
      cooperative. Patients were able to follow the surgeons' verbal cues to thrust out
      the tongue during the procedure, so that the surgeons could easily insert the
      sutures. Conclusions: During the division of the tongue flap in two children,
      excellent sedative and analgesic effects were achieved using continuous
      remifentanil infusion.

PMID- 29457088
TI  - Successful pulmonary embolectomy for massive pulmonary embolism during pregnancy:
      a case report.
AB  - Background: Pulmonary embolism (PE) resulting from venous thromboembolism is a
      leading cause of maternal mortality in pregnancy. In patients with massive PE and
      hemodynamic instability, the treatment options often considered are
      thrombolytics, inferior vena caval filters, or embolectomy. We report here the
      case of a patient with massive PE at 28 weeks' gestation, who underwent emergency
      pulmonary embolectomy via cardiopulmonary bypass. Case presentation: A 35-year
      old primigravida with a history of massive PE at 25 weeks of gestation was
      referred to our hospital at 28 weeks of gestation, following treatment failure
      after insertion of an inferior vena cava filter and heparin administration.
      Emergency thrombectomy was performed, and intracardiac echography was used for
      intraoperative fetal heart rate monitoring. However, the patient developed
      hemodynamic collapse following anesthesia induction; hence, emergency
      cardiopulmonary bypass (CPB) was performed via median sternotomy. Thrombectomy
      and tricuspid valve plication were performed under cardiac arrest. After
      confirming postoperative hemostasis, heparin administration was resumed. At 40
      weeks of gestation, labor was induced under epidural analgesia. Both mother and
      child were discharged with no complications. Conclusion: In conclusion,
      intracardiac echography is useful for fetal heart rate monitoring during
      emergency cardiac surgery in pregnancy. Careful CPB management is important to
      maintain uteroplacental blood flow. Although there is no consensus on the
      delivery methods in such cases, epidural analgesia during labor was useful in
      reducing cardiac load and wound traction.

PMID- 29457089
TI  - A case series of continuous paravertebral block in minimally invasive cardiac
      surgery.
AB  - Background: Minimally invasive cardiac surgery (MICS), via minithoracotomy, is
      thought to be a fast track to extubation and recovery after surgery. For this,
      good coverage analgesia is essential. Epidural anesthesia, a standard technique
      for thoracic surgery, has high risk of complications, such as epidural abscess
      and spinal hematoma in open-heart surgery. Based on the hypothesis that
      continuous paravertebral block (CPVB), a less invasive regional anesthetic
      technique, is safe and effective in open-heart surgery, we applied CPVB to MICS
      with thoracotomy. Findings: To assess whether CPVB could be used in open-heart
      surgery with fewer potential complications, we investigated our medical records
      of the 87 adult patients who underwent MICS at Akashi Medical Center, Hyogo,
      Japan, between March 2009 and May 2016. We collected data of CPVB-related
      complications, postextubation respiratory failure, duration of intubation, and
      other analgesic use from hospital clinical records. We observed no severe CPVB
      related complications, such as hematoma, neuropathy, or abscess. PT-INR longer
      than 1.1 was associated with CPVB-related minor bleeding. Forty-three patients
      (47.4%) were extubated within 1 h after surgery, and there were no postextubation
      respiratory failures in any patients. Conclusions: We observed no cases of severe
      CPVB-related complications or postextubation respiratory failure in any of our
      patients who underwent MICS. Preoperative prolongation of PT-INR was associated
      with CPVB-related minor bleeding.

PMID- 29457090
TI  - Conscious sedation with dexmedetomidine for implantation of a phrenic nerve
      stimulator in a pediatric case of late-onset congenital central hypoventilation
      syndrome.
AB  - Patients with congenital central hypoventilation syndrome (CCHS) develop alveolar
      hypoventilation resulting from a failure of central ventilatory control. Late
      onset CCHS (LO-CCHS), which may be precipitated by severe respiratory infection
      or exposure to sedatives or general anesthesia, presents after the neonatal
      period. Since CCHS patients require lifelong mechanical-assisted ventilation, in
      western countries, diaphragm pacing is used to provide adequate alveolar
      ventilation and oxygenation during rest and daily activities. The main anesthesia
      related concern regarding CCHS is postoperative respiratory failure or apnea, and
      anesthetic agents should be minimized to avoid further respiratory depression
      after surgery. A 5-year-old girl with LO-CCHS was referred to our hospital for
      implantation of a phrenic nerve stimulator for diaphragm pacing. Respiratory
      infection triggered the need for permanent nocturnal ventilator support at age 3
      years and tracheotomy was performed at age 4 years. Repeated self-dislodgement of
      the ventilator tube led to hypoxic ischemic encephalopathy. The patient was
      thought to require mechanical ventilation under minimum sedation and pain
      management during the early postoperative period. The co-administration of
      dexmedetomidine and morphine provided effective conscious sedation with
      protection of the surgical site and without adverse events. She was discharged
      from the intensive care unit with a home ventilator at 3 days post-operation.

PMID- 29457091
TI  - Factors affecting the early post-operative prognosis in morbidly obese surgical
      patients after laparoscopic sleeve gastrectomy - a retrospective cohort study.
AB  - Background: The number of morbidly obese patients who have undergone bariatric
      surgery has been gradually increasing in Japan. These obese patients are often
      complicated with metabolic, cardiac, respiratory, and other diseases. The aim of
      this study was to analyze the perioperative clinical course in a retrospective
      cohort with respect to the utility of anesthesia management in order to prevent
      longer hospital stays after surgery. Findings: Sixty-seven morbidly obese
      patients who had undergone sleeve gastrectomy were divided into two groups, based
      upon the duration of postoperative hospital stay; group S was comprised of the
      patients who were discharged within 5 days after surgery (n = 57) and group L was
      comprised of those who were discharged after 6 days or more (n = 10). The mean
      duration of the hospital stay was 4.8 +/- 0.4 days and 7.8 +/- 1.4 days in groups
      S and L, respectively. Multivariate logistic regression analysis showed that
      prolonged anesthesia was a predictor of a longer postoperative hospital stay (p <
      0.05). While the difference in BMI was not significantly different, the
      percentage of patients with BMI >= 50 was 12 and 30% in groups S and L,
      respectively. Conclusions: Longer duration of anesthesia affected the duration of
      postoperative hospital stay in morbidly obese patients undergoing sleeve
      gastrectomy. In addition, patients with BMI >= 50 might be at risk of longer
      hospitalization after surgery.

PMID- 29457092
TI  - Anesthetic management of one-stage scheduled surgery for adrenal cortical
      carcinoma complicated by massive pulmonary tumor embolism.

PMID- 29457093
TI  - Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are superior to
      other inflammation-based prognostic scores in predicting the mortality of
      patients with gastrointestinal perforation.
AB  - Background: The neutrophil to lymphocyte ratio (NLR) is gaining interest as an
      independent predictor of survival in patients with various clinical conditions.
      No study to date has reported an association between inflammation-based
      prognostic scores, including the Glasgow Prognostic Score (GPS), NLR, platelet to
      lymphocyte ratio (PLR), Prognostic Nutritional Index (PNI), and Prognostic Index
      (PI), and mortality in patients with gastrointestinal perforation (GIP). We
      compared the prognostic value of these measures. Findings: A total of 32 patients
      with GIP were retrospectively enrolled. Patients were assessed according to the
      GPS, NLR, PLR, PI, and PNI. Multivariate analyses were performed to identify
      variables associated with mortality. Receiver operating characteristic (ROC)
      analyses were also performed. Overall survival rates (in-hospital mortality) were
      calculated using the Kaplan-Meier method, and differences in survival rates
      between groups were compared by the log-rank test. Multivariate analysis of
      significant variables revealed NLR (HR 1.257, 95% CI 1.035-1.527, P = 0.021) and
      PLR (HR 1.004, 95% CI 1.001-1.007, P = 0.016) at the time of admission to the
      intensive care unit to be independently associated with in-hospital mortality.
      AUC analysis revealed Sequential Organ Failure Assessment-Glasgow Coma Scale
      (SOFA-GCS) (0.73) to be superior to NLR (0.57) and PLR (0.58) for predicting
      mortality, and a high SOFA-GCS score was associated with reduced overall survival
      (P < 0.05). Conclusions: NLR and PLR were superior to other inflammation-based
      prognostic scores in predicting the mortality of patients with GIP.

PMID- 29457094
TI  - Clinical anatomy of the cephalic vein for safe performance of venipuncture.
AB  - Background: The aims of this study were to elucidate why the cephalic vein
      provides a reliable cannulation site from a morphological viewpoint and identify
      an effective landmark for avoiding injury to the superficial branch of the radial
      nerve (SBRN), allowing for safe venipuncture of the cephalic vein. Findings: We
      examined 32 forearms and wrists from 18 cadavers. The cephalic vein was a
      constant structure containing a branch communicating with a collateral vein of
      the deep palmar arch via the first dorsal interossei muscle. The metacarpal vein
      from the medial two digits flowed into the cephalic vein. The venous confluence
      formed 5.8 +/- 1.2 cm proximal to the radial styloid process. The SBRN passed 0.4
      +/- 0.3 cm volar to the venous confluence. The distance between the venous
      confluence and subcutaneous emergence of the SBRN was 2.6 +/- 1.0 cm.
      Conclusions: These observations suggest that the cephalic vein is a constant
      structure that serves as a drainage vein of the hand and provides a reliable
      cannulation site in the forearm. The venous confluence may serve as a novel
      landmark to predict the running course of the SBRN.

PMID- 29457095
TI  - Iatrogenic carpal tunnel syndrome induced by wrist extension for placement of an
      indwelling radial artery catheter: a case report.
AB  - A 38-year-old man with pancreatic cancer was scheduled to undergo
      pancreaticoduodenectomy. He had an unremarkable past medical history. After
      inducing general anesthesia, a left radial arterial catheter was successfully
      placed at first attempt. A wrist splint was used to obtain good arterial pulse
      waveforms. After the operation, he was transferred to the intensive care unit.
      The radial artery catheter was removed on the fourth postoperative day. He
      experienced numbness and a tingling sensation in the left thumb, the second and
      third fingers, and the lateral half of the fourth finger. He was diagnosed with
      carpal tunnel syndrome. Diagnostic imaging revealed a swollen median nerve, but
      no hematoma or injury. Some studies have suggested that excessive extension of
      the wrist may cause neuropathy. We recommend that patients' wrists not be over
      extended, even if good arterial waveforms cannot be obtained.

PMID- 29457097
TI  - Successful use of femoral nerve block with dexmedetomidine for fracture fixation
      of an intracapsular fracture of the femoral neck in a patient with severe aortic
      stenosis: a case report.
AB  - We described a case in which femoral nerve block (FNB) and lateral femoral
      cutaneous nerve block (LFCNB) with dexmedetomidine (DEX) was useful for open
      reduction and internal fixation (ORIF) of a femoral neck fracture in a patient
      with severe aortic stenosis. Cardiac surgery had been recommended but was
      declined by the patient. Thus, ORIF was selected because of the patient's
      concomitant severe aortic stenosis. The anesthesia method used was FNB plus LFCNB
      with DEX, which achieved adequate local anesthesia. DEX was used to avoid
      respiratory depression because this patient has pulmonary hypertension. This
      patient had been sedative up to the end of surgery. Total operating time was 51
      min, and the patient's hemodynamics were stable throughout the perioperative
      period. There were no complications. In this case, anesthesia using a nerve block
      with DEX contributed to the safety of noncardiac surgery in a patient with severe
      cardiac disease under conservative treatment during the perioperative period.

PMID- 29457096
TI  - Effect of Goreisan, a traditional Japanese Kampo medicine, on postoperative
      nausea and vomiting in gynecological patients.
AB  - Background: Goreisan, a traditional Japanese Kampo medicine, may prevent
      postoperative nausea and vomiting (PONV). The purpose of this study was to
      evaluate the effect of Goreisan on PONV in a high-risk population in a
      randomized, double-blind, placebo-controlled manner. Findings: Patients
      undergoing gynecological surgery were randomly allocated to the Goreisan and the
      control groups. General anesthesia was induced with propofol and remifentanil.
      After endotracheal intubation, anesthesia was maintained with sevoflurane,
      fentanyl, and remifentanil. Goreisan 7.5 g dissolved in water (Goreisan group) or
      water (control group) in a volume of 20 ml was administered through a nasogastric
      tube approximately 1 h before completion of surgery. The primary outcome of this
      study was the incidence of PONV during the first 2 h after extubation. In the
      interim analysis, it was apparent that Goreisan has no effect. Therefore, we
      discontinued recruiting patients and present results based on data from 83
      patients. The incidence of PONV during the first 2 h after extubation was 45% in
      the Goreisan group (n = 40) and 46.5% in the control group (n = 43) (p = 0.89).
      There was no significant difference in PONV incidence or severity during the
      first 24 h post-extubation. Conclusion: Goreisan has little potency in preventing
      PONV in high-risk patients.

PMID- 29457098
TI  - Esophageal submucosal hematoma developed after endovascular surgery for
      unruptured cerebral aneurysm under general anesthesia: a case report.
AB  - Background: Esophageal submucosal hematoma is a rare complication after
      endovascular surgery. We report a case of an esophageal submucosal hematoma which
      may have been caused by rigorous cough during extubation. Case presentation: A 75
      year-old woman underwent endovascular treatment for unruptured cerebral aneurysm
      under general anesthesia. The patient received aspirin and clopidogrel before
      surgery and heparin during surgery. Activated clotting time was 316 s at the end
      of surgery. Protamine was not administered and continuous infusion of argatroban
      was started after surgery. She had a rigorous cough during removal of the
      tracheal tube and reported retrosternal discomfort postoperatively. She developed
      hemorrhagic shock after massive hematemesis. A diagnosis of esophageal submucosal
      hematoma was made by endoscopic examination and computed tomography. Hemostasis
      was achieved by compression with a Sengstaken-Blakemore tube and endoscopic
      cauterization. Blood pressure was recovered by blood transfusion. Endoscopic
      examination performed 7 days after surgery showed that esophageal submucosal
      hematoma had almost disappeared and slough had adhered to the mucosal laceration.
      The patient showed good recovery and was discharged 21 days after surgery.
      Conclusions: Careful extubation and postoperative observation are required in
      patients receiving antiplatelet and anticoagulant therapy.

PMID- 29457099
TI  - Perioperative risk factors for acute kidney injury after off-pump coronary artery
      bypass grafting: a retrospective study.
AB  - Background: Acute kidney injury (AKI) after cardiac surgery is associated with
      increased morbidity and mortality. Although morbidity of AKI after off-pump
      coronary artery bypass grafting (OPCAB) has been investigated, little is known
      about risk factors for AKI after OPCAB. To identify risk factors for AKI, we
      examined the association between perioperative variables and AKI after OPCAB.
      Findings: We reviewed the medical records of consecutive adult patients who
      underwent isolated OPCAB between January 2010 and February 2013 in a single
      institute, retrospectively. The primary outcome was the incidence of AKI
      evaluated using Acute Kidney Injury Network classifications during the first 48 h
      postoperatively. We investigated preoperative and intraoperative variables,
      including hemodynamic parameters, as potential risk factors for AKI. The
      relationship between candidates of AKI and incidence of AKI was examined by
      multivariate logistic regression analysis.A total of 298 patients were enrolled
      in this study. Acute kidney injury occurred in 47 patients (15.7%). Multivariate
      logistic regression analysis showed that intraoperative furosemide administration
      (odds ratio [OR], 5.163; 95% confidence interval, 2.171 to 12.185; P < 0.001] and
      diabetes mellitus (OR, 1.954; 95% confidence interval, 1.004 to 3.880; P = 0.049)
      were significantly associated with AKI. Conclusions: Intraoperative furosemide
      administration and diabetes mellitus were significantly associated with AKI in
      patients who had received OPCAB.

PMID- 29457100
TI  - Differences in heart rate variability may be related to the appearance of
      postoperative pain in patients undergoing breast cancer surgery.
AB  - Background: Some reports have highlighted the relationship between heart rate
      variability (HRV) and the degree of postoperative pain experienced. This study
      retrospectively examined whether differences in heart rate variability may be
      related to the appearance of postoperative pain in patients undergoing breast
      cancer surgery. Findings: We retrospectively analyzed 20 postoperative patients
      who had no pain immediately upon admission to the post-anesthesia care unit
      (PACU), divided into two groups: group A (n = 16) had no pain on admission to
      PACU, remaining pain free upon discharge (12 h after surgery); group B (n = 4)
      comprised patients with no pain on admission to PACU but who experienced
      increasing pain requiring intervention in PACU 1 h after surgery. HRV was
      measured immediately on admission to PACU and 2 h after surgery; this included
      variables of low-frequency power (LF), high-frequency power (HF), and LF/HF.
      There were significant differences in HF and LF/HF in group A compared with those
      in group B on admission to PACU (immediately after arrival): HF, group A, 35.4 +/
      18.1; group B, 64.2 +/- 9.5*; LF/HF group A, 2.7 +/- 2.4; group B, 0.6 +/- 0.2*,
      *p < 0.05). There was no significant difference in the Numerical rating scale
      (NRS) between the two groups immediately after admission to PACU. At 1 h after
      the surgery, NRS in Group B increased, and there were significant differences in
      NRS values between the two groups 1 h after surgery prior to the use of analgesic
      agents (NRS, group A, 1.0 +/- 0.9; group B, 4.0 +/- 1.4*, *p < 0.01). Patients in
      group A required no analgesic agents for at least 12 h after surgery.
      Conclusions: Lower HF and higher LF/HF values immediately after arrival in PACU
      were observed in patients remaining pain free for 12 h after surgery compared to
      patients who experienced increasing postoperative pain 1 h after surgery. The
      data suggest that differences in HRV may be related to the appearance of
      postoperative pain.

PMID- 29457101
TI  - Adhesions in the epidural space caused by frequent epidural blocks.
AB  - We report a case of adhesions in the epidural space caused by more than 200 times
      epidural blocks that were observed with epiduroscopy. A 41-year-old man had
      repeatedly undergone lumbar epidural blocks to treat pain in his leg, resulting
      in decreased efficacy of the epidural block. We described endoscopic findings
      that these adhesions were mostly consisted of adhesions formed from the soft
      connective tissue.

PMID- 29457102
TI  - Incidence of life-threatening respiratory events after laparoscopic colon surgery
      with or without continuous respiratory rate monitoring.
AB  - Background: Respiratory depression (RD) is a critical complication of general
      anesthesia. The present study investigated the incidence of postoperative life
      threatening respiratory events after laparoscopic colon surgery in patients
      observed using continuous respiratory rate monitoring [RM; with oxygen saturation
      by pulse oximetry (SpO2)] and traditional respiratory monitoring (TM; SpO2
      monitoring only). In addition, postoperative incidence rates of RD and
      desaturation in the RM group were determined. Findings: In this retrospective
      observational study, medical records of 214 patients who underwent laparoscopic
      colon surgery were analyzed. A total of 88 patients with RM were observed and
      compared with 126 patients with TM. Nineteen patients in the RM group were
      excluded from the final analyses because of incomplete data. No life-threatening
      respiratory events were observed in the RM group (0/69), whereas two such events
      (2/126) occurred in the TM group. Incidence rates of postoperative RD and
      desaturation within 8 h after surgery were 17.1% (12/69) and 24.3% (17/69),
      respectively, in the RM group. Conclusions: No postoperative life-threatening
      respiratory events were observed in the RM group. Furthermore, the incidence
      rates of RD and desaturation were noted to be relatively high.

PMID- 29457103
TI  - Japanese traditional herbal medicine reduces use of pregabalin and opioids for
      pain in patients with lumbar spinal canal stenosis: a retrospective cohort study.
AB  - Background: There has been an increase in the number of Japanese patients with
      lumbar spinal canal stenosis (LSCS) who complain of chronic pain or motor
      disturbance in the lower back or extremities. These patients are often treated
      with anti-convulsive drugs, opioids, antidepressants, acetaminophen, or
      nonsteroidal anti-inflammatory drugs, all of which can cause side effects. For
      this reason, Japanese traditional herbal medicine (Kampo) is of interest, because
      it produces fewer adverse reactions. The aim of this retrospective cohort study
      was to analyze the effects of Kampo in patients with LSCS. Findings: A total of
      151 patients with LSCS were divided into two groups based on treatment with (n =
      111, group K) and without (n = 40, group N) Kampo. Use of pregabalin and opioids
      decreased significantly in group K (p < 0.001). The hazard ratio for opioid
      discontinuation was 0.220 (p = 0.004) for group N vs. group K, while that for
      pregabalin and antidepressants discontinuation were 0.589 (p = 0.202) and 0.509
      (p = 0.377), respectively. The mean duration of hospital visits and treatment did
      not differ between the groups, but the number of dropouts was significantly
      higher in group N (p < 0.0001). The hazard ratio for patient dropout was 4.118 (p
      = 0.001) for group N vs. group K. Conclusions: Kampo led to discontinuation of
      opioid use for pain in patients with LSCS, and patients who were treated with
      Kampo were more likely to continue treatment.

PMID- 29457104
TI  - Left subclavian artery malperfusion due to thoracic outlet syndrome during total
      vertebrectomy for invasive lung cancer: a case report.
AB  - Thoracic outlet syndrome (TOS) can interrupt blood flow to upper limbs by
      vascular compression. We report a case of a 52-year-old man who presented left
      subclavian artery malperfusion due to TOS during total vertebrectomy (Th2-4) in
      the prone position for invasive lung cancer. At the time of resection of the
      vertebral bodies, his left radial systolic blood pressure had begun to drop
      intermittently and we noticed an interarm pressure difference. Accordingly, we
      began to monitor the right radial artery pressure and found that only the left
      radial artery pressure decreased as a result of compressive force from the
      surgical site. The operation was continued with intermittent malperfusion of the
      left arm, and when it was prolonged, we asked the surgeons to release the
      compression. No symptoms of ischemia or nerve injuries in the left arm were
      observed after the surgery. Retrospective review of his preoperative enhanced
      computed tomography images suggested a slightly compressed left subclavian artery
      in the costoclavicular space. Combination of the prone position and a specific
      upper limb position may be a risk factor for intraoperative TOS. An interarm
      blood pressure difference is a clue to detect accidental arterial TOS during
      general anesthesia.

PMID- 29457106
TI  - Detection of patent ductus arteriosus with intraoperative transesophageal
      echocardiography in a patient undergoing closure of coronary artery to pulmonary
      artery fistula.
AB  - Background: Coronary artery to pulmonary artery fistula is an unusual vascular
      anomaly, and the shunt ratio of this fistula is usually small. Case presentation:
      We report anesthetic management of a 55-year-old female with annuloaortic
      ectasia, aortic valve regurgitation, and coronary artery to pulmonary artery
      fistula undergoing radical repair. We calculated the left-to-right shunt ratio
      after placement of a pulmonary artery catheter and found that the ratio was
      unexpectedly high. Thus, we explored the presence of another shunt by
      intraoperative transesophageal echocardiography and found patent ductus
      arteriosus undiagnosed before operation. Conclusions: A combination of a
      pulmonary artery catheter and transesophageal echocardiography is useful to
      explore the presence of another shunt, such as patent ductus arteriosus during
      anesthesia.

PMID- 29457105
TI  - Collaborating with interventional pulmonology in managing a massive
      tracheoesophageal fistula that extends from cricoid to carina: a case report.
AB  - Tracheoesophageal fistulas (TEF) present a perioperative management challenge. A
      62 year-old man with esophageal carcinoma presented with a large
      tracheoesophageal fistula extending most of the trachea. Previously, the patient
      had two overlapping esophageal and one tracheal stent placed, but he developed
      progressive tracheal disruption due to esophageal stent perforation near the
      level of the cricoid. This case describes the anesthetic management of tracheal
      stent placement for an expanding TEF. Management included a spontaneous breathing
      inhalation induction followed by ventilation through a supraglottic device
      laryngeal mask airway (LMA). Finally, during rigid bronchoscopy, a combination of
      bag ventilation and jet ventilation was utilized.

PMID- 29457107
TI  - The ultrasound-guided nerve blocks of abdominal wall contributed to anesthetic
      management of cholecystectomy in a patient with Becker muscular dystrophy without
      using muscle relaxants.
AB  - Becker muscular dystrophy (BMD) is a progressive neuromuscular disorder caused by
      mutations in the dystrophin gene. The sensitivity to non-depolarizing muscle
      relaxant in a patient with muscle dystrophy is reportedly higher than that in
      normal individuals, and the duration of the effect is known to be prolonged. In
      this report, we present the case of a 58-year-old man with BMD who underwent
      laparoscopic cholecystectomy for symptomatic cholelithiasis under total
      intravenous anesthesia without the use of muscle-relaxant drugs and supplemented
      with regional anesthesia. Anesthesia was induced and maintained with propofol,
      remifentanil, and fentanyl; ultrasound-guided bilateral rectus sheath block (RSB)
      and right-sided subcostal transversus abdominis plane block (TAP) were performed.
      The procedure required conversion to open surgery because of hard conglutination;
      intraoperative and postoperative periods were uneventful. Adequate analgesia was
      maintained after extubation because of the effect of RSB and TAP.

PMID- 29457108
TI  - Continuous PECS II block for postoperative analgesia in patients undergoing
      transapical transcatheter aortic valve implantation.
AB  - It has been reported that PECS II block can alleviate postoperative pain
      following transapical transcatheter aortic valve implantation (TA-TAVI). However,
      the effectiveness of continuous PECS II block with catheterization has not yet
      been reported on the postoperative pain in patients undergoing TA-TAVI. We
      experienced two cases of TA-TAVI who received PECS II block with catheterization
      to manage postoperative pain. In the first case, a bolus injection for
      intraoperative pain and subsequent catheterization were performed before the
      implantation. However, the patient developed severe pain postoperatively in spite
      of the continuous block due to displacement of the catheter. In the second case,
      a bolus injection and the catheterization for the continuous block were performed
      before and after the implantation, respectively, which provided high-quality pain
      control. Continuous PECS II block may be useful to control perioperative pain
      associated with TA-TAVI. The insertion of the catheter after the implantation
      could be useful to avoid its displacement during the surgery.

PMID- 29457109
TI  - Perioperative management of a pregnant patient with mediastinal tumor complicated
      by tuberculosis.
AB  - Mediastinal tumor in a pregnant woman, which had needed a multidisciplinary
      approach, was further complicated by tuberculosis. The clinical course of the
      current patient was very complicated. A 37-year-old female at 18 weeks of
      gestation with a mediastinal tumor was referred to our hospital due to dyspnea
      and orthopnea. The tumor compressed the left main bronchus causing bronchial
      stenosis. She was diagnosed with primary mediastinal large B-cell non-Hodgkin's
      lymphoma. Delivery after 24 gestational weeks with ongoing chemotherapy was
      planned by a multidisciplinary team comprising obstetricians, anesthesiologists,
      neonatologists, and hematologists. Her symptoms improved with chemotherapy;
      however, she was later diagnosed with tuberculosis leading to chemotherapy
      interruption to treat tuberculosis. The following confirmation by negative sputum
      smear microscopy, an elective cesarean section with spinal anesthesia was
      performed at 33 weeks of gestation, and she safely delivered a female infant. At
      postoperative day 23, she died due to cardiopulmonary arrest, following an
      irreversible coma subsequent to brain metastasis of malignant lymphoma. The
      infant died of respiratory failure at postoperative day 18. This case illustrates
      several implications, such as the necessity of a thorough systemic examination
      and treatment approaches for mothers and neonates with suspected tuberculosis
      during the perioperative period, for considering similar cases with neoplasms.

PMID- 29457110
TI  - Anesthetic management for laryngeal closure: retrospective evaluation of 50
      cases.

PMID- 29457111
TI  - Mortality and physical status at hospital discharge in Japanese elderly
      critically ill patients: a single-center retrospective study.
AB  - Background: Because there is ongoing population aging, the age of patients
      admitted to the intensive care unit (ICU) is also higher. However, the evidence
      about outcomes in elderly patients is insufficient in Japan. Therefore, we
      conducted a retrospective study. Method: The study participants were consecutive
      patients who were admitted to our ICU and received mechanical ventilation for
      more than 24 h. We divided the patients into two groups, according to age.
      Patients in group A were 74 years old or younger, and those in group B were 75
      years old or older. The major outcome was in-hospital mortality. Findings: Two
      hundred and twenty patients met the inclusion criteria. There were 118 patients
      in group A and 102 patients in group B. The overall hospital mortality in both
      groups were similar (19 vs. 25%, p = 0.23). The proportion of patients who were
      discharged home and had good physical status at hospital discharge in group A
      were significantly higher than that in group B (72 vs. 37%, p < 0.0001; 91 vs.
      74%, p = 0.004, respectively). Conclusion: The elderly population were associated
      with a twofold increase in the risk of discharged not to the home compared with
      others.

PMID- 29457112
TI  - Anesthetic management during a cesarean section in a patient with cleidocranial
      dysplasia: a case report.
AB  - Background: Cleidocranial dysplasia is a type of skeletal dysplasia, which is
      primarily characterized by delayed ossification of skeletal structures. It causes
      facial and oral abnormalities, resulting in difficult airway management and
      neuraxial anesthesia. Case presentation: The patient was a 24-year-old primipara
      (height 138 cm, weight 42 kg) with a hypoplastic right clavicle, patent
      fontanelles, dental malalignment, and a high palate. She was diagnosed with
      cleidocranial dysplasia at birth, although gene examination has not been
      performed. The fetus was confirmed to have short limbs and large fontanelles
      during an examination performed at 28 weeks gestation, suspected to have
      cleidocranial dysplasia. The mother was scheduled for a cesarean section at 37
      weeks and 1 day due to cephalopelvic disproportion. Preoperative radiography and
      magnetic resonance imaging revealed no vertebral and spinal abnormalities, which
      allowed combined spinal-epidural analgesia (CSEA) to be performed. The surgery
      was safely concluded under CSEA with no intraoperative respiratory or circulatory
      problems. Conclusions: Patients with cleidocranial dysplasia exhibit facial, oral
      abnormalities, and often vertebral abnormalities. Imaging assessments before
      neuraxial anesthesia and careful preparation for airway management are required.

PMID- 29457113
TI  - Pulmonary embolism caused by ovarian vein thrombosis during cesarean section: a
      case report.
AB  - Background: Ovarian vein thrombosis is a rare complication of pregnancy. The
      representative complaints of patients with ovarian vein thrombosis are abdominal
      pain and fever. In some cases, however, fatal pulmonary embolism may develop. We
      report a case of pulmonary embolism presenting with severe hypotension and loss
      of consciousness during cesarean section possibly caused by ovarian vein
      thrombosis. Case presentation: A 25-year-old woman at 38 weeks 4 days of
      gestation was scheduled for repeat cesarean section. Her past history was
      unremarkable, and the progress of her pregnancy was uneventful. She did not
      experience any symptoms indicative of deep vein thrombosis. Cesarean section was
      performed under spinal anesthesia, and a healthy newborn was delivered. After
      removal of the placenta, she suddenly developed dyspnea, hypotension, and loss of
      consciousness with decreased peripheral oxygen saturation. Blood pressure, heart
      rate, and oxygen saturation recovered after tracheal intubation and mechanical
      ventilation with oxygen. Postoperative computed tomography revealed no
      abnormality in the brain or in the pulmonary artery, but a dilated right ovarian
      vein with thrombi, extending up to the inferior vena cava, was found. A diagnosis
      of pulmonary embolism caused by ovarian vein thrombosis was made, and heparin was
      administered. The tracheal tube was removed on the first postoperative day. Her
      postoperative course was uneventful, and she was discharged with no
      complications. Conclusion: Fatal pulmonary embolism might be caused by ovarian
      vein thrombosis during cesarean section. Careful and continuous observation of
      the patient after delivery and prompt treatment are important.

PMID- 29457114
TI  - A pediatric case developing critical abdominal distension caused by a combination
      of humidified high-flow nasal cannula oxygen therapy and nasal airway.
AB  - Background: We describe a pediatric patient who suffered from critical abdominal
      distention caused by a combination of humidified, high-flow nasal cannula (HHFNC)
      oxygen therapy and nasal airway. Case presentation: A 21-month-old boy with a
      history of chronic lung disease was admitted to the intensive care unit (ICU).
      Immediately after admission, his airway was established using a tracheal tube and
      mechanical ventilation was started. Five days after the commencement of
      mechanical ventilation, finally, his trachea was extubated. Immediately after
      extubation, HHFNC therapy at 20 L/min with an FiO2 of 0.35 was applied. However,
      severe stridor was observed, then a nasal airway was placed in the left nostril.
      However, he became restless. Critical abdominal distention was observed. A
      subsequent chest X-ray revealed that the nasal airway was placed too deeply, and
      the gastrointestinal air was severely accumulated. Immediately, the nasal airway
      was removed, and HHFNC flow was reduced to 10 L/min. Frequent suctioning and
      continuous gastric drainage were required, which achieved gradual improvement of
      respiratory condition. Conclusions: We need to recognize that HHFNC therapy is
      one of the positive pressure ventilation system. Therefore, HHFNC therapy might
      cause the similar adverse events to noninvasive pressure ventilation.

PMID- 29457115
TI  - Comparison of inflationary non-invasive blood pressure (iNIBP) monitoring
      technology and conventional deflationary non-invasive blood pressure (dNIBP)
      measurement in detecting hypotension during cesarean section.
AB  - Background: The Nihon Kohden linear inflationary non-invasive blood pressure
      (iNIBP) monitoring technology is an oscillometric device that measures blood
      pressure by detecting oscillations during inflation. Systolic blood pressure can
      be recorded without overinflating the cuff higher than the true systolic
      pressure. Thus, total time taken for inflation and deflation is shorter than that
      by the conventional deflation devices. In this study, the ability of iNIBP to
      detect maternal hypotension during cesarean section faster than deflationary non
      invasive blood pressure (dNIBP) monitoring devices under clinical settings was
      evaluated prospectively. Methods: A prospective study of singleton planned
      cesarean sections at a tertiary center was conducted from August 2015 to April
      2016. The combined spinal-epidural anesthesia (CSEA) technique through a single
      puncture was performed for cesarean section at the center where the study was
      carried out. An iNIBP cuff was placed on the same arm as the intravenous line,
      and a dNIBP cuff was placed on the other arm. Due to left uterine displacement by
      approximately 10 degrees  tilt of OR table, hypotension in this study was defined
      as systolic pressure of 107 mmHg or less, when measured in the left arm, which
      was about 10 cm lower, and pressure of 92 mmHg or less in the right arm which was
      about 10 cm higher. This setup was done to evaluate which device detected
      hypotension faster under clinical settings. A two-tailed Z test was performed to
      statistically analyze the difference between iNIBP and dNIBP measurement results.
      Results: One hundred singleton planned cesarean deliveries under CSEA were
      included after 36 weeks of gestation. Out of the 100, 76 women (76%) experienced
      maternal hypotension. Of these, iNIBP detected hypotension faster than dNIBP in
      47 cases (61.8%). Conclusion: It was found that iNIBP detected hypotension faster
      than conventional dNIBP without compromising the reliability of measurement. This
      may lead to early treatment of maternal hypotension and prevention of adverse
      events related to the mother and the fetus.

PMID- 29457116
TI  - A spinal cord infarction that occurred after laparoscopic gastrectomy performed
      under general anesthesia and epidural analgesia.
AB  - Background: Spinal cord infarction (SCI) after epidural anesthesia is quite rare.
      Although most cases of perioperative SCI are associated with aortic, cardiac, or
      spinal surgery, and/or abnormal preoperative conditions, such as spinal stenosis
      or hypercoagulopathy, intraoperative events, such as severe hypotension or
      epidural puncture and catheterization, can be contributory factors. Case
      presentation: A 52-year-old male was underwent laparoscopic gastrectomy. Before
      induction of general anesthesia, an epidural catheter was placed without any
      problems. The patient had no pain and no complaint just after the operation, but
      suddenly complained of back pain and anuria, and could not move either of his
      lower limbs 30 h after the operation. As we thought that the incident would be
      caused by the migration of the epidural catheter into the subarachnoid space, we
      removed the catheter, but there was no recovery of the symptoms even 20 h later.
      The magnetic resonance imaging (MRI) scan showed no hematoma in the epidural
      space but an abnormal signal within the spinal cord, extending from the Th3 to
      Th8 levels, which was consistent with the SCI. Unfortunately, the patient's
      recovery from the paraplegia and abnormal sensation was poor. Conclusions: When a
      patient complains of lower limb muscle weakness and/or abnormal sensations, it is
      important to perform an MRI examination and treatment as early as possible to
      avoid permanent paraplegia, especially after epidural puncture and
      catheterization.

PMID- 29457117
TI  - Goal-directed therapy reduces fluid balance while maintaining hemodynamic
      stability in intraoperative management of pancreaticoduodenectomy: a
      retrospective comparative study.
AB  - Background: Goal-directed therapy (GDT) is beneficial for surgical patients,
      especially for those undergoing high-risk surgery. However, little has been
      reported on the hemodynamic effects of GDT in extensive surgery. We conducted a
      study to determine the impact of GDT on intraoperative management of extensive
      surgery. Findings: We retrospectively collected data from 90 patients who
      underwent pancreaticoduodenectomy: 44 who received intraoperative GDT (GDT group)
      and 46 who received conventional hemodynamic management (control group).
      Intraoperative use of fluids and catecholamines and physiologic variables,
      including mean arterial pressure, heart rate, and urine output, were compared. We
      also examined the correlation between the amount of fluid administered and urine
      output. The amount of fluid administered was comparable, and urine output was
      significantly larger in the GDT group than in the control group. Fluid balance
      was significantly smaller in the GDT group (49.7 versus 61.7 mL/kg; 95%
      confidence interval, - 19.5 to - 4.6 mL/kg; P = 0.0019). There was a trend toward
      higher mean arterial pressure in the GDT group despite lower fluid balance. We
      found a rank correlation between the amount of fluid administered and urine
      output in the GDT group (rank correlation coefficient, 0.68; P < 0.001), but
      there was no such correlation in the control group. Conclusions: GDT increased
      urine output and decreased fluid balance while maintaining hemodynamic stability.
      The amount of fluid administered and urine output were correlated in the GDT
      group.

PMID- 29457118
TI  - Preoperative elevated FDP may predict severe intraoperative hypotension after
      dural opening during decompressive craniectomy of traumatic brain injury.
AB  - Purpose: Coagulation disorder and intraoperative hypotension are representative
      complications of traumatic brain injury which cause worse perioperative outcome.
      The aim of this study was to survey the relation of coagulation disorder and
      intraoperative hypotension (IH) during decompressive craniectomy. Method:
      Patients who underwent emergency decompressive craniectomy due to traumatic brain
      injury were retrospectively surveyed. The relation between preoperative
      coagulation date and intraoperative hypotension (systolic blood pressure < 60
      mmHg after dural opening) was analyzed. Results: Of 41 patients screened, 12
      patients (27.9%) developed IH. Fibrinogen degradation products (314 vs 64.4
      MUg/mL; p = 0.01) were significantly higher in the IH group. In contrast,
      fibrinogen (181 vs 239 mg/dL; p = 0.01) was significantly lower in the IH group.
      Reduction rate of sBRP before and after dural opening (%) was higher in IH group
      than in non-IH group (49.1 vs 27.6%: p = 0.001). Conclusions: Preoperative
      elevated FDP may predict IH after dural opening during traumatic decompressive
      craniectomy.

PMID- 29457119
TI  - Effects of glucose-insulin infusion during major oral and maxillofacial surgery
      on postoperative complications and outcomes.
AB  - Background: Secretion of hormones, which antagonize the action of insulin, is
      facilitated in response to surgery, and acute resistance to the action of insulin
      develops. Our aim is to elucidate the effects of intraoperative glycemic control
      by glucose-insulin (GI) infusion on postoperative complications and outcomes in
      major oral and maxillofacial surgery. Findings: Thirty patients aged >= 60 years
      undergoing a radical operation of oral malignant tumors with tissue
      reconstruction (>= 8 h) were analyzed. In the GI group, regular insulin was
      continuously applied with glucose-added acetate Ringer's solution (5-10 g glucose
      per 500 mL). Blood glucose was adjusted within the target concentration of 80-120
      mg/dL. In the control group, combination of acetate Ringer's solution containing
      1% (W/V) glucose and lactate Ringer's solution, which contains no glucose, was
      employed. Perioperative clinical parameters, incidence of hypoalbuminemia, and
      postoperative complications, i.e., surgical site infection, necrosis of a
      reconstructed flap, bacteremia, hypotension, or pneumonia, were compared. Both
      serum total protein and albumin concentrations (postoperative day 1 [Day1]) were
      higher in the GI group. The mean infusion rate of glucose during surgery
      (mg/kg/h) was independently associated with the decrease in both serum total
      protein and albumin concentrations from the control to Day1. No difference was
      found between the groups in the incidence of postoperative complications and the
      days required until discharge, except less incidence of hypoalbuminemia in the GI
      group. Conclusions: Application of additional glucose during major oral and
      maxillofacial surgery preserved serum albumin concentration. However, it did not
      lead to less postoperative complications and less days until discharge.

PMID- 29457120
TI  - Spread of injectate in ultrasound-guided serratus plane block: a cadaveric study.
AB  - Background: Serratus plane block is a thoracic truncal block that has been
      proposed as alternatives for analgesia such as epidural anesthesia and
      paravertebral block for the anterolateral chest wall. Previously, we performed
      the clinical study about optimal volume of the local anesthetic in serratus plane
      block. The primary aim of this study was to assess the pattern of distribution of
      dye into the serratus plane of cadavers after ultrasound-guided serratus plane
      injection. Findings: Ultrasound-guided serratus plane injection was performed at
      the level of the fourth rib on the mid-axillary line in nine adult Thiel-embalmed
      cadavers. In each cadaver, one side was injected with 20 ml of methylene blue dye
      and the contralateral side with 40 ml. Dissections of the thoracic walls were
      performed 20 min after the injection. The spread of the dye to intercostal
      nerves, lateral and medial pectoral nerves, long thoracic nerve, and
      thoracodorsal nerves was assessed. All T2-T5 intercostal nerves in the 40-ml
      group and all T3-T4 nerves in the 20-ml group were stained with the dye. A larger
      number of intercostal nerves was stained in the 40-ml group than that in the 20
      ml group. Medial and lateral pectoral nerves were not frequently stained in
      either group. Conclusions: The range of craniocaudal spread of the injectate was
      wider in the 40-ml group than that in the 20-ml group after ultrasound-guided
      serratus plane injection in Thiel-embalmed cadavers.

PMID- 29457121
TI  - Anesthesia for patients with PTRF mutations: a case report.
AB  - Background: Polymeraze I and transcript release factor (PTRF) mutations are a
      newly recognized disease, which cause congenital generalized lipodystrophy
      associated with myopathy. Case presentation: A 29-year-old man (height 126 cm;
      weight 22 kg) with a PTRF mutation was scheduled for mandibular dentigerous
      cystectomy. His primary symptoms were lipodystrophy, myopathy, long QT syndrome,
      refractory nephrosis, and abnormal lipid metabolism. Defibrillator pads were
      applied soon after the patient entered the operating room. Anesthesia was induced
      using continuous administration of dexmedetomidine (4 MUg/kg/h) for 15 min;
      midazolam (7 mg) was added while monitoring the bispectral index and his vital
      signs. Remifentanil and rocuronium were administered before endotracheal
      intubation. The surgeon used local anesthesia, and dexmedetomidine and
      remifentanil were titrated throughout the surgery. The surgery was performed
      uneventfully, and the patient was extubated following the administration of
      sugammadex and flumazenil. Conclusion: Patients with PTRF mutations require
      careful anesthetic planning. We planned to administer lipid-free, non
      inhalational agents for the induction and maintenance of anesthesia. The
      anesthetic method used for this minor surgery was safe and effective.

PMID- 29457122
TI  - A case of spinal anesthesia in a patient with progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is one of the rare diseases. PSP is
      characterized by oculomotor dysfunction, postural instability, akinesia,
      dysarthria, and dysphagia. The major cause of death in patients with PSP is
      aspiration pneumonia. Considering these complications, spinal anesthesia is
      useful in patients with PSP. However, the potential harmful effects of spinal
      anesthesia including neurotoxicity of local anesthetics and neurologic
      complications for patients with PSP are unclear, because there has been no
      report. Here, we present spinal anesthesia for a patient with PSP. An 80-year-old
      man with progressive oculomotor dysfunction, dysphagia, and history of repeated
      aspiration pneumonia was scheduled for inguinal hernia surgery. Acutely
      concerning about perioperative pulmonary complications, we performed spinal
      anesthesia. Fortunately, there was no complication associated with respiration or
      neural system during perioperative period. We hope our experience and case report
      will be helpful in specific perioperative anesthetic care for patients with PSP.

PMID- 29457123
TI  - General anesthesia with propofol for ovarian teratoma excision associated with
      anti-N-methyl-D-aspartate receptor encephalitis.
AB  - Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder
      caused by production of anti-NMDAR antibodies that is often associated with
      ovarian teratoma and exhibits various manifestations including psychiatric
      symptoms, seizures, hypoventilation, and autonomic nerve instability. Patients
      with this disorder who receive early surgical tumor resection along with
      immunotherapy have better outcome than the rest of the patients. To establish an
      anesthetic plan, it is important to understand the pharmacological interaction
      between the anesthetic agents and the disabled NMDAR, because NMDAR is one of the
      major sites of action for commonly-used anesthetic agents. Herein, we describe
      two young female patients with anti-NMDAR encephalitis who required surgical
      resection of ovarian teratoma under general anesthesia using propofol,
      remifentanil, and fentanyl. In both of these anesthetic courses, neither
      psychoneuronal modification nor autonomic instability by propofol was evident.
      Furthermore, propofol has been reported to suppress the effects of ketamine on
      the posterior cingulate cortices, which is the area of the brain concerned with
      psychotomimetic activity and neural damage of NMDAR antagonists. Our cases imply
      that propofol is safely used in patients with anti-NMDAR encephalitis, although
      it has some pharmacological effects on NMDAR.

PMID- 29457124
TI  - Dilated aortic root influences pulmonary artery catheter placement in
      anesthetized patients.
AB  - Purpose: The placement of a pulmonary artery catheter sometimes needs long time
      by observing the pressure wave, and several factors have been reported to hinder
      the placement. In the present study, we examined whether enlargement of the
      aortic root is associated with longer time for the placement. Method: We examined
      the time required for the catheter placement. The catheter placement time was
      defined as the duration of time required for the catheter to float from the CVP
      position to the pulmonary artery. The catheter placement was performed by one
      experienced physician. We examined the following factors on the catheter
      placement time: the patient's age, height, weight, cardiothoracic ratio,
      tricuspid regurgitation, ejection fraction and the diameter of aortic annulus,
      sinus of Valsalva, sinotubular junction, and proximal ascending aorta. These
      diameter values were divided by body surface area (BSA) to equalize among
      different physical sizes. The data were analyzed by multiple linear regression
      analysis after univariate analysis. Results: The univariate analysis showed that
      ejection fraction and aortic annulus/BSA, sinus of Valsalva/BSA, and sinotubular
      junction/BSA correlated with the catheter placement time (P = 0.079, 0.030,
      0.029, and 0.025, respectively). Since the three aortic root values correlated
      with each other, we chose the sinotubular junction/BSA for the following
      multivariate analysis, because of the highest P value. The multivariate analysis
      showed that sinotubular junction/BSA had a significant positive association with
      the placement time (P = 0.048). Conclusion: The present study showed that
      enlargement of the aortic root is associated with long placement time of the
      catheter.

PMID- 29457125
TI  - Enhanced differentiation of dental pulp cells cultured on microtubular polymer
      scaffolds in vitro.
AB  - : Dental caries (tooth decay) is the most common chronic disease. Dental tissue
      engineering is a promising alternative approach to alleviate the shortcomings of
      the currently available restorative materials. Mimicking the natural
      extracellular matrix (ECM) could enhance the performance of tissue engineering
      scaffolds. In this study, we developed microtubular (~20 MUm diameter) polymethyl
      methacrylate (PMMA) scaffolds resembling the tubular (~2.5 MUm diameter)
      structure of dentin, the collagen-based mineralized tissue that forms the major
      portion of teeth, to study the effect of scaffold architecture on differentiation
      of mouse dental pulp cells in vitro. Flat (control), plasma-treated solid and
      microtubular PMMA scaffolds with densities of 240+/-15, 459+/-51 and 480+/-116
      tubules/mm2 were first characterized using scanning electron microscopy and
      contact angle measurements. Dental pulp cells were cultured on the surface of the
      scaffolds for up to 21 days and examined using various assays. Cell proliferation
      and mineralization were examined using Alamar Blue and Xylenol Orange (XO)
      staining assays, respectively. The differentiation of pulp cells into
      odontoblasts was examined by immunostaining for Nestin and by quantitative PCR
      analysis for dentin matrix protein 1 (Dmp1), dentin sialophosphoprotein (Dspp)
      and osteocalcin (Ocn). Our results showed that the highest tubular density
      scaffolds significantly (p<0.05) enhanced differentiation of pulp cells into
      odontoblasts as compared to control flat scaffolds, as evidenced by increased
      expression of Nestin (5.4x). However, mineralization was suppressed on all
      surfaces, possibly due to low cell density. These results suggest that the
      microtubular architecture may be a desirable feature of scaffolds developed for
      clinical applications. Lay Summary: Regenerative engineering of diseased or
      traumatized tooth structure could avoid the deficiencies of traditional dental
      restorative (filling) materials. Cells in the dental pulp have the potential to
      differentiate to dentin-producing odontoblast cells. Furthermore, cell-supporting
      scaffolds that mimic a natural extracellular matrix (ECM) are known to influence
      behavior of progenitor cells. Accordingly, we hypothesized that a dentin-like
      microtubular scaffold would enhance differentiation of dental pulp cells. The
      hypothesis was proven true and differentiation to odontoblasts increased with
      increasing density of the microtubules. However, mineralization was suppressed,
      possibly due to a low density of cells. The results demonstrate the potential
      benefits of a microtubular scaffold design to promote odontoblast cells for
      regeneration of dentin.

PMID- 29457126
TI  - Using Predictive Evaluation to Design, Evaluate, and Improve Training for Polio
      Volunteers.
AB  - Background: Predictive Evaluation (PE) uses a four-step process to predict
      results then designs and evaluates a training intervention accordingly. In 2012,
      the Sustainable Management Development Program (SMDP) at the Centers for Disease
      Control and Prevention used PE to train Stop Transmission of Polio (STOP) program
      volunteers. Methods: Stakeholders defined specific beliefs and practices that
      volunteers should demonstrate. These predictions and adult learning practices
      were used to design a curriculum to train four cohorts. At the end of each
      workshop, volunteers completed a beliefs survey and wrote goals for intended
      actions. The goals were analyzed for acceptability based on four PE criteria. The
      percentage of acceptable goals and the beliefs survey results were used to define
      the quality of the workshop. A postassignment adoption evaluation was conducted
      for two cohorts, using an online survey and telephone or in-person structured
      interviews. The results were compared with the end of workshop findings. Results:
      The percentage of acceptable goals across the four cohorts ranged from 49% to
      85%. In the adoption evaluation of two cohorts, 88% and 94% of respondents
      reported achieving or making significant progress toward their goal. A comparison
      of beliefs survey responses across the four cohorts indicated consistencies in
      beliefs that aligned with stakeholders' predictions. Conclusions: Goal statements
      that participants write at the end of a workshop provide data to evaluate
      training quality. Beliefs surveys surface attitudes that could help or hinder
      workplace performance. The PE approach provides an innovative framework for
      health worker training and evaluation that emphasizes performance.

PMID- 29457127
TI  - Polyethylenimine-dermatan sulfate complex, a bioactive biomaterial with unique
      toxicity to CD146-positive cancer cells.
AB  - We report unique bioactivity of a polycation-polyanion complex with potential
      utility for cancer therapy. A complex of disulfide-crosslinked polyethyleneimine
      (CLPEI), a polycation used for gene complexation, and dermatan sulfate (DS), an
      anionic polysaccharide to shield excessive cationic charge of the former, has
      toxicity to a specific group of cancer cell lines, including B16-F10 murine
      melanoma, A375SM human melanoma, and PC-3 human prostate cancer cells. These
      CLPEI-DS-sensitive cells express CD146, which binds to the complex via
      interaction with DS. There is a positive correlation between toxicity and
      intracellular level of CLPEI, indicating that the CLPEI-DS-sensitivity is
      attributable to the increased cellular uptake of CLPEI mediated by the DS-CD146
      interactions. In vitro studies show that CLPEI-DS complex causes G0/G1 phase
      arrest and apoptotic cell death. In syngeneic and allograft models of B16-F10
      melanoma, CLPEI-DS complex administered with a sub-toxic level of doxorubicin
      potentiates the chemotherapeutic effect of the drug by loosening tumor tissues.
      Given the unique toxicity, CLPEI-DS complex may be a useful carrier of gene or
      chemotherapeutics for the therapy of CD146-positive cancers.

PMID- 29457128
TI  - Evaluation of Hydrogels Presenting Extracellular Matrix-Derived Adhesion Peptides
      and Encapsulating Cardiac Progenitor Cells for Cardiac Repair.
AB  - Cell therapy is an emerging paradigm for the treatment of heart disease. In spite
      of the exciting and promising preclinical results, the benefits of cell therapy
      for cardiac repair in patients have been modest at best. Biomaterials-based
      approaches may overcome the barriers of poor differentiation and retention of
      transplanted cells. In this study, we prepared and tested hydrogels presenting
      extracellular matrix (ECM)-derived adhesion peptides as delivery vehicles for c
      kit+ cardiac progenitor cells (CPCs). We assessed their effects on cell behavior
      in vitro as well as cardiac repair in rats undergoing ischemia reperfusion.
      Hydrogels presenting the collagen-derived GFOGER peptide induced cardiomyocyte
      differentiation of CPCs as demonstrated by increased expression of cardiomyocyte
      structural proteins. However, conditioned media obtained from GFOGER hydrogels
      showed lower levels of secreted reparative factors. Interestingly, following
      injection in rats undergoing ischemia-reperfusion, treatment with CPCs
      encapsulated in nonadhesive RDG-presenting hydrogels resulted in the preservation
      of cardiac contractility and attenuation of postinfarct remodeling whereas the
      adhesion peptide-presenting hydrogels did not induce any functional improvement.
      Retention of cells was significantly higher when delivered with nonadhesive
      hydrogels compared to ECM-derived peptide gels. These data suggest that factors
      including cell differentiation state, paracrine factors and interaction with
      biomaterials influence the effectiveness of biomaterials-based cell therapy. A
      holistic consideration of these multiple variables should be included in cell
      biomaterial combination therapy designs.

PMID- 29457130
TI  - Prevalence and Social Determinants of Type 2 Diabetes in a Coastal Area of
      Kerala, India.
AB  - Introduction: Varying prevalence rates of type 2 diabetes have been observed in
      different parts of the southern state of Kerala, India which is in an advanced
      stage of epidemiologic transition. Social patterning is evident in diabetes and
      therefore it was decided to undertake a study on estimating the prevalence of
      diabetes and associated social determinants. Methodology: The adopted local self
      administration unit of the Medical College which is also the field practice area
      with a population of 25,096 was taken for the study. All the households in the
      area were visited and the details regarding self reported diabetes was collected
      after obtaining informed consent and analysis done by multivariate logistic
      regression. Result: The prevalence of self reported diabetes in this coastal area
      was found to be low at 7.4%. Type 2 diabetes was also found to occur
      significantly earlier among the respondents belonging to the below poverty line.
      Age above 40 years (OR 2 95% CI 1.5-2.7, p=.000), marital status (OR 1.9 95% CI
      1.1-2.1, p=.006) presence of comorbidities (OR 635 95% CI 389-969, p=.000), more
      than 8 years of schooling (OR 0.64 95% CI 0.46-0.86, p=.004), living conditions
      as represented by presence of household source of drinking water(OR 1.4 95% CI
      1.01-1.5) were found to be independent predictors. Though there was increasing
      trend of diabetes among the forward caste line families after backward logistic
      regression this disappeared leaving behind the proxy of socioeconomic status,
      household source of drinking water. Conclusion: Though, the state of Kerala is in
      an advanced stage of epidemiologic transition, coastal areas are still in the
      earlier phases of transition with low prevalence of type 2 diabetes mellitus.
      Higher education and better living conditions are important social determinants
      of diabetes though further studies are necessary to delineate the impact of
      economic status and education.

PMID- 29457129
TI  - In Vitro Modeling of Mechanics in Cancer Metastasis.
AB  - In addition to a multitude of genetic and biochemical alterations, abnormal
      morphological, structural, and mechanical changes in cells and their
      extracellular environment are key features of tumor invasion and metastasis.
      Furthermore, it is now evident that mechanical cues alongside biochemical signals
      contribute to critical steps of cancer initiation, progression, and spread.
      Despite its importance, it is very challenging to study mechanics of different
      steps of metastasis in the clinic or even in animal models. While considerable
      progress has been made in developing advanced in vitro models for studying
      genetic and biological aspects of cancer, less attention has been paid to models
      that can capture both biological and mechanical factors realistically. This is
      mainly due to lack of appropriate models and measurement tools. After introducing
      the central role of mechanics in cancer metastasis, we provide an outlook on the
      emergence of novel in vitro assays and their combination with advanced
      measurement technologies to probe and recapitulate mechanics in conditions more
      relevant to the metastatic disease.

PMID- 29457132
TI  - Scattered wave imaging of the oceanic plate in Cascadia.
AB  - Fifty years after plate tectonic theory was developed, the defining mechanism of
      the plate is still widely debated. The relatively short, simple history of young
      ocean lithosphere makes it an ideal place to determine the property that defines
      a plate, yet the remoteness and harshness of the seafloor have made precise
      imaging challenging. We use S-to-P receiver functions to image discontinuities
      beneath newly formed lithosphere at the Juan de Fuca and Gorda Ridges. We image a
      strong negative discontinuity at the base of the plate increasing from 20 to 45
      km depth beneath the 0- to 10-million-year-old seafloor and a positive
      discontinuity at the onset of melting at 90 to 130 km depth. Comparison with
      geodynamic models and experimental constraints indicates that the observed
      discontinuities cannot easily be reconciled with subsolidus mechanisms. Instead,
      partial melt may be required, which would decrease mantle viscosity and define
      the young oceanic plate.

PMID- 29457133
TI  - Unprecedented climate events: Historical changes, aspirational targets, and
      national commitments.
AB  - The United Nations Paris Agreement creates a specific need to compare
      consequences of cumulative emissions for pledged national commitments and
      aspirational targets of 1.5 degrees  to 2 degrees C global warming. We find that
      humans have already increased the probability of historically unprecedented hot,
      warm, wet, and dry extremes, including over 50 to 90% of North America, Europe,
      and East Asia. Emissions consistent with national commitments are likely to cause
      substantial and widespread additional increases, including more than fivefold for
      warmest night over ~50% of Europe and >25% of East Asia and more than threefold
      for wettest days over >35% of North America, Europe, and East Asia. In contrast,
      meeting aspirational targets to keep global warming below 2 degrees C reduces the
      area experiencing more than threefold increases to <10% of most regions studied.
      However, large areas-including >90% of North America, Europe, East Asia, and much
      of the tropics-still exhibit sizable increases in the probability of record
      setting hot, wet, and/or dry events.

PMID- 29457134
TI  - Trophic signatures of seabirds suggest shifts in oceanic ecosystems.
AB  - Pelagic ecosystems are dynamic ocean regions whose immense natural capital is
      affected by climate change, pollution, and commercial fisheries. Trophic level
      based indicators derived from fishery catch data may reveal the food web status
      of these systems, but the utility of these metrics has been debated because of
      targeting bias in fisheries catch. We analyze a unique, fishery-independent data
      set of North Pacific seabird tissues to inform ecosystem trends over 13 decades
      (1890s to 2010s). Trophic position declined broadly in five of eight species
      sampled, indicating a long-term shift from higher-trophic level to lower-trophic
      level prey. No species increased their trophic position. Given species prey
      preferences, Bayesian diet reconstructions suggest a shift from fishes to squids,
      a result consistent with both catch reports and ecosystem models. Machine
      learning models further reveal that trophic position trends have a complex set of
      drivers including climate, commercial fisheries, and ecomorphology. Our results
      show that multiple species of fish-consuming seabirds may track the complex
      changes occurring in marine ecosystems.

PMID- 29457135
TI  - Oceanic crustal carbon cycle drives 26-million-year atmospheric carbon dioxide
      periodicities.
AB  - Atmospheric carbon dioxide (CO2) data for the last 420 million years (My) show
      long-term fluctuations related to supercontinent cycles as well as shorter cycles
      at 26 to 32 My whose origin is unknown. Periodicities of 26 to 30 My occur in
      diverse geological phenomena including mass extinctions, flood basalt volcanism,
      ocean anoxic events, deposition of massive evaporites, sequence boundaries, and
      orogenic events and have previously been linked to an extraterrestrial mechanism.
      The vast oceanic crustal carbon reservoir is an alternative potential driving
      force of climate fluctuations at these time scales, with hydrothermal crustal
      carbon uptake occurring mostly in young crust with a strong dependence on ocean
      bottom water temperature. We combine a global plate model and oceanic paleo-age
      grids with estimates of paleo-ocean bottom water temperatures to track the
      evolution of the oceanic crustal carbon reservoir over the past 230 My. We show
      that seafloor spreading rates as well as the storage, subduction, and emission of
      oceanic crustal and mantle CO2 fluctuate with a period of 26 My. A connection
      with seafloor spreading rates and equivalent cycles in subduction zone rollback
      suggests that these periodicities are driven by the dynamics of subduction zone
      migration. The oceanic crust-mantle carbon cycle is thus a previously overlooked
      mechanism that connects plate tectonic pulsing with fluctuations in atmospheric
      carbon and surface environments.

PMID- 29457131
TI  - Keeping an Eye on Bardet-Biedl Syndrome: A Comprehensive Review of the Role of
      Bardet-Biedl Syndrome Genes in the Eye.
AB  - Upwards of 90% of individuals with Bardet-Biedl syndrome (BBS) display rod-cone
      dystrophy with early macular involvement. BBS is an autosomal recessive,
      genetically heterogeneous, pleiotropic ciliopathy for which 21 causative genes
      have been discovered to date. In addition to retinal degeneration, the cardinal
      features of BBS include obesity, cognitive impairment, renal anomalies,
      polydactyly, and hypogonadism. Here, we review the genes, proteins, and protein
      complexes involved in BBS and the BBS model organisms available for the study of
      retinal degeneration. We include comprehensive lists for all known BBS genes,
      their known phenotypes, and the model organisms available. We also review the
      molecular mechanisms believed to lead to retinal degeneration. We provide an
      overview of the mode of inheritance and describe the relationships between BBS
      genes and Joubert syndrome, Leber Congenital Amaurosis, Senior-Loken syndrome,
      and non-syndromic retinitis pigmentosa. Finally, we propose ways that new
      advances in technology will allow us to better understand the role of different
      BBS genes in retinal formation and function.

PMID- 29457136
TI  - Unexpected evolutionary benefit to phages imparted by bacterial CRISPR-Cas9.
AB  - Bacteria and bacteriophages arm themselves with various defensive and
      counterdefensive mechanisms to protect their own genome and degrade the other's.
      CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR
      associated) is an adaptive bacterial defense mechanism that recognizes short
      stretches of invading phage genome and destroys it by nuclease attack.
      Unexpectedly, we discovered that the CRISPR-Cas system might also accelerate
      phage evolution. When Escherichia coli bacteria containing CRISPR-Cas9 were
      infected with phage T4, its cytosine hydroxymethylated and glucosylated genome
      was cleaved poorly by Cas9 nuclease, but the continuing CRISPR-Cas9 pressure led
      to rapid evolution of mutants that accumulated even by the time a single plaque
      was formed. The mutation frequencies are, remarkably, approximately six orders of
      magnitude higher than the spontaneous mutation frequency in the absence of CRISPR
      pressure. Our findings lead to the hypothesis that the CRISPR-Cas might be a
      double-edged sword, providing survival advantages to both bacteria and phages,
      leading to their coevolution and abundance on Earth.

PMID- 29457137
TI  - Correcting Nonpathological Variation in Longitudinal Parametric Response Maps of
      CT Scans in COPD Subjects: SPIROMICS.
AB  - Small airways disease (SAD) is one of the leading causes of airflow limitations
      in patients diagnosed with chronic obstructive pulmonary disease (COPD).
      Parametric response mapping (PRM) of computed tomography (CT) scans allows for
      the quantification of this previously invisible COPD component. Although PRM is
      being investigated as a diagnostic tool for COPD, variability in the longitudinal
      measurements of SAD by PRM has been reported. Here, we show a method for
      correcting longitudinal PRM data because of non-pathological variations in serial
      CT scans. In this study, serial whole-lung high-resolution CT scans over a 30-day
      interval were obtained from 90 subjects with and without COPD accrued as part of
      SPIROMICS. It was assumed in all subjects that the COPD did not progress between
      examinations. CT scans were acquired at inspiration and expiration, spatially
      aligned to a single geometric frame, and analyzed using PRM. By modeling
      variability in longitudinal CT scans, our method could identify, at the voxel
      level, shifts in PRM classification over the 30-day interval. In the absence of
      any correction, PRM generated serial percent volumes of functional SAD with
      differences as high as 15%. Applying the correction strategy significantly
      mitigated this effect with differences ~1%. At the voxel-level, significant
      differences were found between baseline PRM classifications and the follow-up map
      computed with and without correction (P <. 01 over GOLD). This strategy of
      accounting for nonpathological sources of variability in longitudinal PRM may
      improve the quantification of COPD phenotypes transitioning with disease
      progression.

PMID- 29457138
TI  - Leveraging the Learning Health Care Model to Improve Equity in the Age of Genomic
      Medicine.
AB  - To fully achieve the goals of a genomics-enabled learning health care system,
      purposeful efforts to understand and reduce health disparities and improve equity
      of care are essential. This paper highlights three major challenges facing
      genomics-enabled learning health care systems, as they pertain to ancestrally
      diverse populations: inequality in the utility of genomic medicine; lack of
      access to pharmacogenomics in clinical care; and inadequate incorporation of
      social and environmental data into the electronic health care record (EHR). We
      advance a framework that can not only be used to directly improve care for all
      within the learning health system, but can also be used to focus on the needs to
      address racial and ethnic health disparities and improve health equity.

PMID- 29457139
TI  - Enhanced n-Doping Efficiency of a Naphthalenediimide-Based Copolymer through
      Polar Side Chains for Organic Thermoelectrics.
AB  - N-doping of conjugated polymers either requires a high dopant fraction or yields
      a low electrical conductivity because of their poor compatibility with molecular
      dopants. We explore n-doping of the polar naphthalenediimide-bithiophene
      copolymer p(gNDI-gT2) that carries oligoethylene glycol-based side chains and
      show that the polymer displays superior miscibility with the benzimidazole
      dimethylbenzenamine-based n-dopant N-DMBI. The good compatibility of p(gNDI-gT2)
      and N-DMBI results in a relatively high doping efficiency of 13% for n-dopants,
      which leads to a high electrical conductivity of more than 10-1 S cm-1 for a
      dopant concentration of only 10 mol % when measured in an inert atmosphere. We
      find that the doped polymer is able to maintain its electrical conductivity for
      about 20 min when exposed to air and recovers rapidly when returned to a nitrogen
      atmosphere. Overall, solution coprocessing of p(gNDI-gT2) and N-DMBI results in a
      larger thermoelectric power factor of up to 0.4 MUW K-2 m-1 compared to other NDI
      based polymers.

PMID- 29457140
TI  - H2 Evolution with Covalent Organic Framework Photocatalysts.
AB  - Covalent organic frameworks (COFs) are a new class of crystalline organic
      polymers that have garnered significant recent attention as highly promising H2
      evolution photocatalysts. This Perspective discusses the advances in this field
      of energy research while highlighting the underlying peremptory factors for the
      rational design of readily tunable COF photoabsorber-cocatalyst systems for
      optimal photocatalytic performance.

PMID- 29457142
TI  - Cross-country Association of Press Freedom and LGBT freedom with prevalence of
      persons living with HIV: implication for global strategy against HIV/AIDS.
AB  - Background: Human behaviors are affected by attitudes and beliefs, which in turn
      are shaped by higher-level values to which we have ascribed. In this study, we
      explore the relationship between two higher-level values, press freedom and LGBT
      freedom, and HIV infection with national data at the population level. Methods:
      Data were the number of persons living with HIV (PLWH, n = 35,468,911) for 148
      countries during 2011-15, press freedom index (PFI) determined by the Reporters
      Without Borders, and LGBT freedom index (LGBT-FI) based on laws regulating same
      sex relationships and expression. PLWH prevalence (1/1000), PFI and LGBT-FI were
      mapped first. Multiple regression was thus used to associate the logarithm of
      PLWH prevalence with PFI, LGBT-FI and PFI * LGBT-FI interaction, controlling for
      per capita GDP and weighted by population size. Results: Global prevalence of
      PLWH during 2011-15 was 0.51 per 1000 population. The prevalence showed a
      geographic pattern moving from high at the south and west ends of the world map
      to low at the north and east. Both PFI and LGBT-FI were positively associated
      with PLWH prevalence with a negative interaction between the two. Conclusions:
      More people are infected with HIV in countries with higher press freedom and
      higher LGBT freedom. Furthermore, press freedom can attenuate the positive
      association between levels of LGBT freedom and risk of HIV infection. This study
      demonstrated the urgency for and provided data supporting further research to
      investigate potential cultural and socioecological mechanisms underpinning the
      complex relationship among press freedom, LGBT freedom and HIV infection, with
      data collected at the individual level.

PMID- 29457143
TI  - Reciprocity in ROS and autophagic signaling.
AB  - Reactive oxygen species (ROS) are important signaling molecules that mediate
      oxidative stress and cellular damage when improperly regulated. ROS and oxidative
      stress can activate autophagy, which generally serves as a cytoprotective
      negative feedback mechanism to selectively eliminate sources of ROS, including
      mitochondria and peroxisomes. In this review we describe the mechanisms by which
      ROS directly and indirectly activate autophagy, and conversely, how selective
      autophagy suppresses the formation of ROS. Furthermore, we highlight what appear
      to be contradictory examples in which ROS suppress, rather than activate,
      autophagy; and where selective autophagy promotes, rather than inhibits ROS
      production, thereby contributing to cell death. Given that ROS are implicated in
      cancer, diabetes, atherosclerosis, neurodegenerative diseases and
      ischemia/reperfusion injury, a deeper understanding of the connections linking
      ROS and autophagy is greatly needed.

PMID- 29457141
TI  - EXTRAHEPATIC TOXICITY OF ACETAMINOPHEN: CRITICAL EVALUATION OF THE EVIDENCE AND
      PROPOSED MECHANISMS.
AB  - Research on acetaminophen (APAP) toxicity over the last several decades has
      focused on the pathophysiology of liver injury, but increasing attention is being
      paid to other known and possible adverse effects. It has been known for decades
      that APAP causes acute kidney injury, but confusion exists regarding prevalence,
      and the mechanisms have not been well investigated. More recently, a number of
      experimental, clinical and epidemiological studies have reported evidence for
      pulmonary, endocrine, neurological and neurodevelopmental toxicity, but the
      quality of evidence from those studies varies. It is important to consider these
      data due to implications for regulation and clinical practice. Here, we review
      the evidence and proposed mechanisms for extrahepatic adverse effects of APAP and
      weigh weaknesses and strengths in the data. We consider results from clinical,
      epidemiological and experimental research. Our goal is to determine the strength
      of claims regarding extrahepatic toxicity of APAP and to identify areas of need
      for future research. It is especially important to view claims of developmental
      effects of antenatal APAP exposure with a critical eye because APAP is currently
      the only over-the-counter medication recommended for pregnant women to self-treat
      pain and fever.

PMID- 29457144
TI  - Functional Near Infrared Spectroscopy: Enabling Routine Functional Brain Imaging.
AB  - Functional Near-Infrared Spectroscopy (fNIRS) maps human brain function by
      measuring and imaging local changes in hemoglobin concentrations in the brain
      that arise from the modulation of cerebral blood flow and oxygen metabolism by
      neural activity. Since its advent over 20 years ago, researchers have exploited
      and continuously advanced the ability of near infrared light to penetrate through
      the scalp and skull in order to non-invasively monitor changes in cerebral
      hemoglobin concentrations that reflect brain activity. We review recent advances
      in signal processing and hardware that significantly improve the capabilities of
      fNIRS by reducing the impact of confounding signals to improve statistical
      robustness of the brain signals and by enhancing the density, spatial coverage,
      and wearability of measuring devices respectively. We then summarize the
      application areas that are experiencing rapid growth as fNIRS begins to enable
      routine functional brain imaging.

PMID- 29457145
TI  - Fourier-Domain Analysis of the Iterative Landweber Algorithm.
AB  - This paper proposes a novel method of using the frequency-domain transfer
      function to investigate the property of an iterative algorithm for minimizing a
      quadratic objective function. This paper focuses on a two-dimensional (2D)
      tomography problem, which can be X-ray computed tomography (CT), positron
      emission tomography (PET), and single photon emission computed tomography
      (SPECT). Two questions regarding to the linear iterative Landweber algorithm are
      considered. The first question is whether stopping early is equivalent to getting
      a minimum-norm solution. The second question is whether the low frequency
      components always converge first. Our answers to these two questions are No.

PMID- 29457146
TI  - Periodontal Biology: Stem Cells, Bmp2 Gene, Transcriptional Enhancers, and Use of
      Sclerostin Antibody and Pth for Treatment of Periodontal Disease and Bone Loss.
AB  - The periodontium is a complex tissue with epithelial components and a complex set
      of mesodermal derived alveolar bone, cellular and a cellular cementum, and tendon
      like ligaments (PDL). The current evidence demonstrates that the major pool of
      periodontal stem cells is derived from a population of micro vascular associated
      aSMA-positive stem/progenitor (PSC) cells that by lineage tracing form all three
      major mesodermal derived components of the periodontium. With in vitro aSMA+ stem
      cells, transcriptome and chip- seq experiments, the gene network and enhancer
      maps were determined at several differentiation states of the PSC. Current work
      on the role of the Bmp2 gene in the periodontal stem cell differentiation
      demonstrated that this Wnt regulated gene, Bmp2, is necessary for differentiation
      to all three major mesodermal derived component of the periodontium. The
      mechanism and use of Sclerostin antibody as an activator of Wnt signaling and
      Bmp2 gene as a potential route to treat craniofacial bone loss is discussed. As
      well, the mechanism and use of Pth in the treatment of periodontal bone loss or
      other craniofacial bone loss is presented in this review.

PMID- 29457147
TI  - A Scoping Review of Health Outcomes Examined in Randomized Controlled Trials
      Using Guided Imagery.
AB  - Introduction: Guided imagery involves the controlled visualization of detailed
      mental images. This integrative health technique is used for healing, health
      maintenance, or the treatment of specific conditions. Guided imagery is an
      integral part of mindfulness meditation, hypnosis, and various relaxation
      exercises. However, evidence to support the widespread use and dissemination of
      guided imagery interventions has been lacking. The purposes of this scoping
      review were to document the scope of health outcomes and disease processes
      examined by guided imagery researchers and the journal outlets where this work
      has been published. Secondary purposes were to review the efficacy of guided
      imagery, risk of bias from studies published in selected integrative health
      journals, and gain feedback from clinicians in a practiced-based research network
      (PBRN) about potential barriers for use in clinical settings. Methods: Ten
      bibliographic databases were searched for randomized controlled trials (RCTs)
      published between 1960 and 2013 that included adult participants. Descriptive and
      analytic methods were employed to document the journal outlets, diseases, and
      health outcomes investigated. Results: 320 RCTs that included more than 17,979
      adult participants were reviewed. The published studies appeared in 216 peer
      reviewed journals from diverse disciplines largely representing psychology, the
      sport sciences, rehabilitation, nursing, and medicine. Major outcomes observed
      were coping with pain, stroke recovery, anxiety, coping with stress, and sport
      skills. Practitioner feedback from the PBRN revealed some interest but skepticism
      and time constraints were discussed as barriers. Conclusions: Ongoing research
      and creative dissemination techniques are warranted.

PMID- 29457148
TI  - Platelets at the Vascular Interface.
AB  - In this brief review paper, we will summarize the State-of-the-Art on how
      platelet reactivity is regulated in circulation and at sites of vascular injury.
      Our review discusses recent and ongoing work, presented at this year's
      International Society on Thrombosis and Haemostasis (ISTH) meeting, on the role
      of platelets in (1) classical hemostasis at sites of mechanical injury, and (2)
      the maintenance of vascular integrity at sites of inflammation.

PMID- 29457149
TI  - Working Memory Training in Adolescents Decreases Laboratory Risk Taking in the
      Presence of Peers.
AB  - Adolescence is a period of heightened risk-taking relative to both adulthood and
      childhood, due in part to peers' increased influence on adolescent decision
      making. Because adolescents' choices have harmful consequences, there is great
      interest in specific interventions that might attenuate risk taking. We
      hypothesized that it might be possible to reduce adolescent risk taking through
      an intervention targeting the ability/tendency to engage cognitive control
      processes. While some studies of Working Memory Training (WMT) have indicated
      subsequent enhancement of adults' cognitive control abilities, potential impacts
      on adolescent cognitive control have not been explored. Accordingly, we tested
      whether four weeks of WMT (relative to Active Control Training, ACT) might
      increase performance on cognitive control measures and decrease risk-taking in
      adolescents. Adolescents receiving WMT, compared to those receiving ACT,
      exhibited some evidence of improved short-term memory performance following the 4
      week training period. Improvements did not significantly transfer to performance
      on basic cognitive control measures. However, on two risk-taking tasks
      administered at post-training either with or without an anonymous peer audience,
      adolescents who received WMT evinced suppressed levels of risk taking when
      observed by peers, an effect not seen in ACT. Further work is needed to more
      fully characterize the potential of WMT interventions in stemming risk behavior
      within adolescent samples.

PMID- 29457150
TI  - The links between agriculture, Anopheles mosquitoes, and malaria risk in children
      younger than 5 years in the Democratic Republic of the Congo: a population-based,
      cross-sectional, spatial study.
AB  - Background: The relationship between agriculture, Anopheles mosquitoes, and
      malaria in Africa is not fully understood, but it is important for malaria
      control as countries consider expanding agricultural projects to address
      population growth and food demand. Therefore, we aimed to assess the effect of
      agriculture on Anopheles biting behaviour and malaria risk in children in rural
      areas of the Democratic Republic of the Congo (DR Congo). Methods: We did a
      population-based, cross-sectional, spatial study of rural children (<5 years) in
      the DR Congo. We used information about the presence of malaria parasites in each
      child, as determined by PCR analysis of dried-blood spots from the 2013-14 DR
      Congo Demographic and Health Survey (DHS). We also used data from the DHS, a
      longitudinal entomological study, and available land cover and climate data to
      evaluate the relationships between agriculture, Anopheles biting behaviour, and
      malaria prevalence. Satellite imagery was used to measure the percentage of
      agricultural land cover around DHS villages and Anopheles sites. Anopheles biting
      behaviour was assessed by Human Landing Catch. We used probit regression to
      assess the relationship between agriculture and the probability of malaria
      infection, as well as the relationship between agriculture and the probability
      that a mosquito was caught biting indoors. Findings: Between Aug 13, 2013, and
      Feb 13, 2014, a total of 9790 dried-blood spots were obtained from the DHS, of
      which 4612 participants were included in this study. Falciparum malaria infection
      prevalence in rural children was 38.7% (95% uncertainty interval [UI] 37.3-40.0).
      Increasing exposure to agriculture was associated with increasing malaria risk
      with a high posterior probability (estimate 0.07, 95% UI -0.04 to 0.17; posterior
      probability [estimate >0]=0.89), with the probability of malaria infection
      increased between 0.2% (95% UI -0.1 to 3.4) and 2.6% (-1.5 to 6.6) given a 15%
      increase in agricultural cover, depending on other risk factors. The models
      predicted that large increases in agricultural cover (from 0% to 75%) increase
      the probability of infection by as much as 13.1% (95% UI -7.3 to 28.9). Increased
      risk might be due to Anopheles gambiae sensu lato, whose probability of biting
      indoors increased between 11.3% (95% UI -15.3 to 25.6) and 19.7% (-12.1 to 35.9)
      with a 15% increase in agriculture. Interpretation: Malaria control programmes
      must consider the possibility of increased risk due to expanding agriculture.
      Governments considering initiating large-scale agricultural projects should
      therefore also consider accompanying additional malaria control measures.
      Funding: National Institutes of Health, National Science Foundation, Bill &
      Melinda Gates Foundation, President's Malaria Initiative, and Royster Society of
      Fellows at the University of North Carolina at Chapel Hill.

PMID- 29457152
TI  - Minimax Rate-optimal Estimation of KL Divergence between Discrete Distributions.
AB  - We refine the general methodology in [1] for the construction and analysis of
      essentially minimax estimators for a wide class of functionals of finite
      dimensional parameters, and elaborate on the case of discrete distributions with
      support size S comparable with the number of observations n. Specifically, we
      determine the "smooth" and "non-smooth" regimes based on the confidence set and
      the smoothness of the functional. In the "non-smooth" regime, we apply an
      unbiased estimator for a "suitable" polynomial approximation of the functional.
      In the "smooth" regime, we construct a bias corrected version of the Maximum
      Likelihood Estimator (MLE) based on Taylor expansion. We apply the general
      methodology to the problem of estimating the KL divergence between two discrete
      distributions from empirical data. We construct a minimax rate-optimal estimator
      which is adaptive in the sense that it does not require the knowledge of the
      support size nor the upper bound on the likelihood ratio. Moreover, the
      performance of the optimal estimator with n samples is essentially that of the
      MLE with n ln n samples, i.e., the effective sample size enlargement phenomenon
      holds.

PMID- 29457153
TI  - Sparse Multi-view Task-Centralized Learning for ASD Diagnosis.
AB  - It is challenging to derive early diagnosis from neuroimaging data for autism
      spectrum disorder (ASD). In this work, we propose a novel sparse multi-view task
      centralized (Sparse-MVTC) classification method for computer-assisted diagnosis
      of ASD. In particular, since ASD is known to be age- and sex-related, we
      partition all subjects into different groups of age/sex, each of which can be
      treated as a classification task to learn. Meanwhile, we extract multi-view
      features from functional magnetic resonance imaging to describe the brain
      connectivity of each subject. This formulates a multi-view multi-task sparse
      learning problem and it is solved by a novel Sparse-MVTC method. Specifically, we
      treat each task as a central task and other tasks as the auxiliary ones. We then
      consider the task-task and view-view relations between the central task and each
      auxiliary task. We can use this task-centralized strategy for a highly efficient
      solution. The comprehensive experiments on the ABIDE database demonstrate that
      our proposed Sparse-MVTC method can significantly outperform the existing
      classification methods in ASD diagnosis.

PMID- 29457151
TI  - The Impact of IgG transplacental transfer on early life immunity.
AB  - Pediatric vaccines have significantly reduced infectious disease-related infant
      mortality, but as protective immunity often require several infant vaccine doses;
      maternally-acquired antibodies are critical to protect infants during the first
      months of life. Consequently, immunization of pregnant women is an important
      strategy not only to protect mothers from infection, but also to provide immunity
      to young infants. Nevertheless, maternal immunization can also negatively impact
      early life immunity. In fact, maternal antibodies can interfere with the
      development of infant immune responses, though it is unclear if such interference
      is clinically significant. Moreover, the transplacental transfer of maternal
      immunoglobulin therapeutics can be harmful to the fetus. Thus, the risk/benefit
      of maternal immunization for both the mother and the fetus should be carefully
      weighed. In addition, it is critical to fully understand the mechanisms by which
      IgG is transferred across the placenta in order to develop optimal maternal and
      infant immunization strategies.

PMID- 29457154
TI  - Motion-Robust Spatially Constrained Parameter Estimation in Renal Diffusion
      Weighted MRI by 3D Motion Tracking and Correction of Sequential Slices.
AB  - In this work, we introduce a novel motion-robust spatially constrained parameter
      estimation (MOSCOPE) technique for kidney diffusion-weighted MRI. The proposed
      motion compensation technique does not require a navigator, trigger, or breath
      hold but only uses the intrinsic features of the acquired data to track and
      compensate for motion to reconstruct precise models of the renal diffusion
      signal. We have developed a technique for physiological motion tracking based on
      robust state estimation and sequential registration of diffusion sensitized
      slices acquired within 200ms. This allows a sampling rate of 5Hz for state
      estimation in motion tracking that is sufficiently faster than both respiratory
      and cardiac motion rates in children and adults, which range between 0.8 to
      0.2Hz, and 2.5 to 1Hz, respectively. We then apply the estimated motion
      parameters to data from each slice and use motion-compensated data for 1) robust
      intra-voxel incoherent motion (IVIM) model estimation in the kidney using a
      spatially constrained model fitting approach, and 2) robust weighted least
      squares estimation of the diffusion tensor model. Experimental results, including
      precision of IVIM model parameters using bootstrap-sampling and in-vivo whole
      kidney tractography, showed significant improvement in precision and accuracy of
      these models using the proposed method compared to models based on the original
      data and volumetric registration.

PMID- 29457155
TI  - VIGAN: Missing View Imputation with Generative Adversarial Networks.
AB  - In an era when big data are becoming the norm, there is less concern with the
      quantity but more with the quality and completeness of the data. In many
      disciplines, data are collected from heterogeneous sources, resulting in multi
      view or multi-modal datasets. The missing data problem has been challenging to
      address in multi-view data analysis. Especially, when certain samples miss an
      entire view of data, it creates the missing view problem. Classic multiple
      imputations or matrix completion methods are hardly effective here when no
      information can be based on in the specific view to impute data for such samples.
      The commonly-used simple method of removing samples with a missing view can
      dramatically reduce sample size, thus diminishing the statistical power of a
      subsequent analysis. In this paper, we propose a novel approach for view
      imputation via generative adversarial networks (GANs), which we name by VIGAN.
      This approach first treats each view as a separate domain and identifies domain
      to-domain mappings via a GAN using randomly-sampled data from each view, and then
      employs a multi-modal denoising autoencoder (DAE) to reconstruct the missing view
      from the GAN outputs based on paired data across the views. Then, by optimizing
      the GAN and DAE jointly, our model enables the knowledge integration for domain
      mappings and view correspondences to effectively recover the missing view.
      Empirical results on benchmark datasets validate the VIGAN approach by comparing
      against the state of the art. The evaluation of VIGAN in a genetic study of
      substance use disorders further proves the effectiveness and usability of this
      approach in life science.

PMID- 29457156
TI  - Effect of Calcium Hydroxide on Bonding Performance of an Experimental Self-etch
      Adhesive.
AB  - PURPOSE: To investigate the effect of Ca(OH)2 concentration on pH neutralization,
      degree of conversion (DC%), and bonding performance of experimental self-etch
      adhesives (SEAs). MATERIALS AND METHODS: Four different concentrations of Ca(OH)2
      (0 wt%, 1 wt%, 2 wt%, and 4 wt%) were added to the bond of an experimental two
      step SEA consisting of primer (10-MDP [30 wt%], TEG-DMA [30 wt%], ethanol [35
      wt%], water [5 wt%], camphorquinone [0.5 wt%], and tertiary amine [0.5 wt%]) and
      bond (bis-GMA [50 wt%], TEG-DMA [30 wt%], HEMA [20 wt%], camphorquinone [0.5
      wt%], and tertiary amine [0.5 wt%]) to form four groups: E0, E1, E2 and E4. pH
      neutralization was evaluated until it reached equilibrium, and DC% within the
      hybrid layer was analyzed by micro-Raman spectroscopy. Human molars were wet
      ground until the occlusal dentin was exposed, SEAs were applied, and composite
      buildups were constructed. After storage in distilled water at 37 degrees C for
      24 h, the teeth were cut into composite-dentin beams. Microtensile bond strength
      (uTBS) was evaluated after 24 h of water storage at 37 degrees C. Nanoleakage was
      evaluated by SEM. Data were analyzed using ANOVA and Tukey's HSD test (a = 0.05).
      RESULTS: All the SEAs reached pH equilibrium after thirteen days, with E1 and E4
      presenting the highest pH (p < 0.05). E0 and E1 presented lower DC% than did E2
      and E4 (p < 0.05). All the SEAs showed statistically similar mTBS and nanoleakage
      (p > 0.05). CONCLUSION: The incorporation of Ca(OH)2 endowed the SEAs with pH
      neutralization ability and improved their DC%, without interfering with the bond
      strength to dentin or nanoleakage extent.

PMID- 29457157
TI  - Visible Light Curing Devices - Irradiance and Use in 302 German Dental Offices.
AB  - PURPOSE: To determine the irradiance delivered by visible-light curing (VLC)
      units and obtain information about the exposure times and the maintenance
      protocols used by dentists. MATERIALS AND METHODS: The irradiance (mW/cm2)
      delivered by 526 VLCs from 302 dental offices from the Rhine-Main area, Germany,
      was measured using an integrating sphere (IS) and a MARC patient simulator (M
      PS); additional information was gathered using a survey. RESULTS: Irradiance was
      measured from 117 standard quartz-tungsten-halogen (QTH), 5 high-power QTH, 2 LED
      1st-generation, 333 LED 2nd-generation, 61 LED 3rd-generation, and 8 plasma-arc
      curing (PAC) units. Depending on the measurement method, 8% (IS) or 11% (M-PS) of
      the VLCs delivered < 400 mW/cm2. Depending on the VLC, the shortest exposure
      times required to deliver a radiant exposure of 16 J/cm2 ranged from 7 to 294 s.
      The number of exposure cycles used by dentists when light curing a restoration
      ranged from 1 to 14. The shortest total exposure time used by dentists on a
      restoration was 5 s, the maximum was 200 s, and the median was 20 s. Of the 526
      VLCs, 41% had intact, undamaged light tips. Only half of the dental offices
      checked the irradiance from their VLCs regularly, 97% disinfected the VLC, and
      86% used eye protection. CONCLUSION: Approximately 10% of the VLCs delivered <
      400 mW/cm2 and 14% of the dental offices used no form of eye protection. To
      achieve sufficient light curing of RBC restorations, more awareness about the
      VLCs used in the dental office is required.

PMID- 29457158
TI  - Structural and dynamic properties of 1-butyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide/mica and graphite interfaces revealed by
      molecular dynamics simulation.
AB  - It has been observed that the properties of room temperature ionic liquids near
      solid substrates are different from those of bulk liquids, and these properties
      play an important role in the development of catalysts, lubricants, and
      electrochemical devices. In this paper, we report microscopic studies of ionic
      liquid/solid interfaces performed using molecular dynamics simulations. The
      structural and dynamic properties of 1-butyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide (BMIM-TFSI) on mica and graphite interfaces
      were thoroughly investigated to elucidate the microscopic origins of the
      formation of layered structures at the interfaces. Our investigation included the
      observation of structural and orientational changes of ions as a function of
      distance from the surfaces, and contour mappings of ions parallel and
      perpendicular to the surfaces. By virtue of such detailed analyses, we found
      that, during the 5 ns simulation, the closest layer of BMIM-TFSI behaves as a two
      dimensional ionic crystal on mica and as a liquid or liquid crystal on graphite.

PMID- 29457159
TI  - Gadolinium based endohedral metallofullerene Gd2@C79N as a relaxation boosting
      agent for dissolution DNP at high fields.
AB  - We show increased dynamic nuclear polarization by adding a low dosage of a S =
      15/2 Gd based endohedral metallofullerene (EMF) to DNP samples. By adding 60 MUM
      Gd2@C79N, the nuclear polarization of 1H and 13C spins from 40 mM 4-oxo-TEMPO
      increases by approximately 40% and 50%, respectively, at 5 T and 1.2 K. Electron
      electron double resonance (ELDOR) measurements show that the high spin EMF
      shortens the electron relaxation times and increases electron spectral diffusion
      leading to the increased DNP enhancement.

PMID- 29457160
TI  - Interfacial growth of metal-organic framework membranes on porous polymers via
      phase transformation.
AB  - A novel single-step approach, named phase transformation interfacial growth
      (PTIG), was developed for the fabrication of metal-organic framework membranes on
      polymeric substrates. Both the separation layer and the substrate were formed
      within the PTIG process. This innovative methodology paves a way for fabricating
      high-quality MOF membranes.

PMID- 29457161
TI  - A self-supported amorphous Ni-P alloy on a CuO nanowire array: an efficient 3D
      electrode catalyst for water splitting in alkaline media.
AB  - Energy-efficient electrochemical water splitting is one important way to produce
      hydrogen fuel but still faces many challenges. In this communication, we report
      that an amorphous Ni-P alloy shell electrodeposited on a CuO nanowire array
      supported on copper foam (CuO@Ni-P NA/CF) can be used for efficient water
      splitting in alkaline media. As a 3D catalytic electrode, it exhibits excellent
      activity both for the hydrogen evolution reaction (HER) and the oxygen evolution
      reaction (OER) with overpotentials of 106 mV for HER and 275 mV for OER to
      achieve a current density of 30 mA cm-2 in 1.0 M KOH. This bifunctional electrode
      enables a high-performance alkaline water electrolyzer to achieve a current
      density of 30 mA cm-2 at a cell voltage of 1.71 V.

PMID- 29457162
TI  - An efficient approach for enhancing the catalytic activity of Ni-MOF-74 via a
      relay catalyst system for the selective oxidation of benzylic C-H bonds under
      mild conditions.
AB  - Although nickel-based materials exhibit similar catalytic activity to palladium
      in organic synthesis, the selective oxidation of inert C-H bonds in the absence
      of other co-catalysts remains a largely unsolved challenge. This paper introduces
      a facile and efficient approach for enhancing the catalytic activity of Ni-MOF-74
      with [bmim]Br via a relay catalysis strategy, which is excellent for the
      selective oxidation of benzylic C-H bonds. Notably, the catalyst recycling and
      scale up experiments demonstrated the practicability of the protocol. This method
      combines the catalytic advantages of MOFs and ionic liquids (ILs), and provides
      an insight into oxidation reactions by cheap and efficient Ni-based catalysts.

PMID- 29457163
TI  - Probing energy losses from dye desorption in cobalt complex-based dye-sensitized
      solar cells.
AB  - Self-assembly of organic sensitizer layers in cobalt complex-based DSCs was
      studied to elucidate its role in reducing the loss of charge recombination. DSCs
      with various dye loadings were fabricated by dye desorption without the aid of
      basic solvent. The FT-IR and UV results indicate the deprotonation of the
      anchoring organic sensitizers, which influences the conduction band of TiO2
      remarkably by changing the surface potential. Positive band edge shifts and a
      decrease of the recombination rate constant are demonstrated to be the main
      factors affecting energy loss at open circuit. In contrast, absorbed photon
      conversion efficiency (APCE) analyses illuminate the crucial role of the packing
      of the anchoring sensitizer in reducing recombination loss at short circuit. This
      is further supported by numerical simulations, which show that APCE is primarily
      dependent on the recombination rate constant rather than the band edge shift at
      short circuit. These results highlight the importance of self-assembly of
      sensitizers with insulating groups in retarding charge recombination by forming
      overlapping molecular layers.

PMID- 29457164
TI  - Effect on absorption and electron transfer by using Cd(ii) or Cu(ii) complexes
      with phenanthroline as auxiliary electron acceptors (A) in D-A-pi-A motif
      sensitizers for dye-sensitized solar cells.
AB  - To broaden the absorption spectrum, improve intramolecular electronic push-pull
      balance capability, enhance electron transfer and promote the photovoltaic
      performances of dye sensitizers, four new polymeric metal complex dyes (PBDTT
      PhenCd, PBDTT-PhenCu, PPV-PhenCd and PPV-PhenCu) with donor-acceptor-pi-bridge
      acceptor (D-A-pi-A) structure were designed and synthesized. These dyes, for the
      first time, used the complexes of Cd(ii) or Cu(ii) with phenanthroline as
      auxiliary electron acceptors (A) instead of organic electron withdrawing groups
      and adopted thienylbenzo [1,2-b:4,5-b'] dithiophene (BDTT) or hydroquinone (PV)
      derivatives as electron donors (D) and 8-quinolinol derivatives as pi bridge and
      acceptors (A). The impacts of different auxiliary electron acceptors (A) of metal
      complexes due to their thermal, optical, electrochemical properties and
      photovoltaic performance were also investigated. The best power conversion
      efficiency of 6.68% was achieved in PBDTT-PhenCd DSSC device. In addition, all
      dyes showed outstanding thermal stability (Td > 300  degrees C). The results
      revealed that these novel polymeric metal complex dyes are potential materials
      for constructing new sensitizers of high performance.

PMID- 29457165
TI  - New porous monolithic membranes based on supported ionic liquid-like phases for
      oil/water separation and homogenous catalyst immobilisation.
AB  - Porous monolithic advanced functional materials based on supported ionic liquid
      like phase (SILLP) systems were used for the preparation of oleophilic and
      hydrophobic cylindrical membranes and successfully tested as eco-friendly and
      safe systems for oil/water separation and for the continuous integration of
      catalytic and separation processes in an aqueous-organic biphasic reaction
      system.

PMID- 29457166
TI  - A vibrational circular dichroism (VCD) methodology for the measurement of
      enantiomeric excess in chiral compounds in the solid phase and for the
      complementary use of NMR and VCD techniques in solution: the camphor case.
AB  - For the first time, the success of a methodology for the determination of
      enantiomeric excess (% ee) in chiral solid samples by vibrational circular
      dichroism (VCD) spectroscopy is reported. We have used camphor to determine the %
      ee in a blind sample constituted by a mixture of its two enantiomers as a test
      for the validity of our approach. IR and VCD spectra of different enantiomeric
      mixtures of R/S-camphor in Nujol mulls were recorded and linear regressions of
      VCD intensities (DeltaAbs.) vs. % ee for selected bands were found. Finally, the
      VCD intensities of a blind sample were interpolated in these linear regressions,
      obtaining its % ee with a rms of 2.4. These results in the solid phase were
      complemented with the determination of % ee in the liquid phase by VCD and NMR
      techniques, which are proved to be complementary techniques to carry out this
      kind of analysis. In the same way as in the VCD solid phase, linear regressions
      of DeltaAbs. vs. % ee for selected bands were established, obtaining a rms of 1.1
      in the % ee determination of a blind sample. 1H NMR experiments at 600 MHz using
      the chiral solvating agent, (S,S)-ABTE, allow the determination of the
      proportions of enantiomers in CD2Cl2 solution with great accuracy. 13C CPMAS NMR
      spectra prove that this technique cannot be used for conglomerates and/or solid
      solutions.

PMID- 29457167
TI  - Improved thermoelectric properties of PEDOT:PSS polymer bulk prepared using spark
      plasma sintering.
AB  - : A low-density PEDOT:PSS/inorganic nanoparticle composite bulk material was
      prepared by carrying out spark plasma sintering (SPS) at 100  degrees C. A PEDOT:
      PSS sample with 33 wt% Cu2SnSe3 nanoparticles showed the highest ZT of the
      samples tested, with a value of 0.04 at 45  degrees C and 20 times higher than
      the 0.002 value of a pristine PEDOT:PSS bulk sample.

PMID- 29457168
TI  - Spatially resolved coding of lambda-orthogonal hydrogels by laser lithography.
AB  - A lambda-orthogonal reaction system is introduced, where visible light induced
      radical thiol-ene and UV light induced NITEC (Nitrile-Imine mediated Tetrazole
      Ene Conjugation) ligations are consecutively employed to fabricate and
      functionalize PEG-based hydrogels. The fluorescent pyrazoline cycloadducts from
      the NITEC reaction are exploited to visualize the written structures within the
      hydrogels as well as to attach RGD containing functional groups to promote
      spatially resolved cell attachment on the hydrogel surface.

PMID- 29457169
TI  - Tracking mitochondrial pH fluctuation during cell apoptosis with two-photon
      phosphorescent iridium(iii) complexes.
AB  - Two iridium(iii) complexes with ligands containing morpholine groups were used to
      track mitochondrial pH fluctuation during cell apoptosis as their emissive
      intensities linearly increased with increase in pH values.

PMID- 29457170
TI  - Sensitive detection of alkaline phosphatase by dephosphorylation-initiated
      transcription reaction-mediated dual signal amplification.
AB  - We develop a new fluorescence method for the sensitive detection of alkaline
      phosphatase (ALP) based on dephosphorylation-initiated transcription reaction
      mediated dual signal amplification. This research demonstrates for the first time
      a significant improvement in ALP assay performance by using a nucleic acid
      amplification strategy, which enables sensitive detection of ALP activity in
      vitro and in cell extracts. Importantly, this method can be further applied for
      kinetic analysis and ALP inhibition assay.

PMID- 29457171
TI  - Exploiting coordination geometry to selectively predict the sigma-donor and pi
      acceptor abilities of ligands: a back-and-forth journey between electronic
      properties and spectroscopy.
AB  - Through an analysis of eighty tetrahedral and square-planar metal carbonyls of
      general formula [M(CO)(L')(L)2] including newly synthesized chlorocarbonyl
      rhodium complexes with chelating atropoisomeric diphosphanes, we show how
      coordination geometry can switch the carbonyl stretching frequency into a
      selective probe of the sigma-donor and pi-acceptor abilities of the ligands. We
      thus provide a framework whereby the sigma-donation and pi-backdonation
      constituents of the Dewar-Chatt-Duncanson model can be quantitatively predicted
      through spectroscopic data on coordinated CO moieties and vice versa.

PMID- 29457172
TI  - Inorganic mixed phase templated by a fatty acid monolayer at the air-water
      interface: the Mn and Mg case.
AB  - We studied by means of Grazing Incidence X-ray Diffraction (GIXD) coupled with X
      ray fluorescence spectroscopy the structure of a behenic acid monolayer spread at
      the surface of Mg2+/Mn2+ mixed aqueous solutions. For the pure Mg2+ and Mn2+
      aqueous solutions, the cations induce at the surface different 2D lattice
      superstructures of the organic monolayer. These superstructures correspond to an
      inorganic organized monolayer anchored to the hydrophilic group of the ordered
      behenic acid monolayer. Among the various diffraction peaks, we focused on those
      characteristics of the behenic acid oblique cell. As the Mg2+ mole fraction x
      increases in the Mg2+/Mn2+ mixed subphase, a continuous evolution of the oblique
      cell parameters is observed indicating the insertion of Mg2+ cations in the Mn2+
      ordered monolayer. Then, a further increase leads to the appearance of a
      coexistence between two oblique surface phases. The cell parameters of both
      phases evolve continuously along the x range of the transition until a single Mg
      rich ordered phase is detected. However, although the intensities of the peaks in
      the coexistence region are in agreement with a first-order phase transition, the
      cell parameters evolve simultaneously. Considering a thermodynamics analysis,
      this evidences that, apart from the concentration, another unidentified intensive
      parameter is varying. We suggest that it is the ionic strength, which appears to
      be strongly related to the concentrations.

PMID- 29457173
TI  - Aqueous TMAO solutions as seen by theoretical THz spectroscopy: hydrophilic
      versus hydrophobic water.
AB  - Solvation of trimethylamine-N-oxide (TMAO) by water is of great fundamental
      interest because this small molecule has both strongly hydrophilic and large
      hydrophobic groups at its opposite ends and, furthermore, stabilizes proteins
      against temperature and pressure denaturation. Since hydrophilic and hydrophobic
      groups affect the structural dynamics of the respective solvation water molecules
      in vastly different ways, we dissect their distinct influences on the THz
      spectrum of TMAO(aq) by using ab initio molecular dynamics simulations. In
      particular, we demonstrate that exclusively electronic polarization and charge
      transfer effects, being absent in the usual fixed-charge biomolecular force
      fields, are responsible for the significant enhancement of the effective
      molecular dipole moment of hydrophilic solvation water. This, in turn, leads to
      pronounced solute-solvent couplings and thus to specific THz modes that involve
      well-defined H-bond bending and stretching motion being characteristic to
      hydrophilic solvation. The THz response of individual H-bonded pairs of water
      molecules involving hydrophobic solvation water, in stark contrast, is nearly
      indistinguishable from such pairs in bulk water. Transcending the specific case,
      THz spectroscopy is suggested to be an ideal experimental approach to unravel the
      controversial piezolytic properties of TMAO including its counteracting effect on
      pressure-induced denaturation of proteins.

PMID- 29457174
TI  - Dynamic modulation of inter-particle correlation during colloidal assembly in a
      confined medium: revealed by real time SAXS.
AB  - Using real time small-angle X-ray scattering, we ellucidate a hitherto unobserved
      non-monotonic evolution of inter-particle correlation while colloidal particles
      assemble across pore boundary in a confined medium under influence of solvent
      evaporation. Time variation of local volume fraction of the particles passes
      through distinct modulation prior to reaching equilibrium. It has been
      demonstrated that the amplitude of oscillation depends strongly on size of the
      assembling particles. We comprehend such non-linear temporal evolution of
      particle correlation through density functional theory and molecular dynamics
      simulation.

PMID- 29457175
TI  - Tetrabenzo-Chichibabin's hydrocarbons: substituent effects and unusual
      thermochromic and thermomagnetic behaviours.
AB  - Open-shell pi-conjugated compounds have recently received intense attention due
      to their unique properties and promising applications in materials science.
      However, the experiments on how the substituents affect their chemical bonding
      and structural motif remain less addressed. In this work, a series of tetrabenzo
      Chichibabin's hydrocarbon (TBC) derivatives substituted by different electron
      donating or -withdrawing groups at the termini were synthesized. The substituent
      effect was studied via X-ray crystallographic analysis. The strong electron
      donating dimethylamino-group substituted TBC derivative underwent simultaneous
      oxidation to give two cyanine-like moieties at the termini. More interestingly,
      it exhibited unusual thermochromic and thermomagnetic behaviours.

PMID- 29457176
TI  - Effect of HU protein on the conformation and compaction of DNA in a nanochannel.
AB  - The effect of the heat unstable nucleoid structuring protein HU on the
      conformation of single DNA molecules confined in a nanochannel was investigated
      with fluorescence microscopy. Pre-incubated DNA molecules contract in the
      longitudinal direction of the channel with increasing concentration of HU. This
      contraction is mainly due to HU-mediated bridging of distal DNA segments and is
      controlled by channel diameter as well as ionic composition and strength of the
      buffer. For over-threshold concentrations of HU, the DNA molecules compact into
      an condensed form. Divalent magnesium ions facilitate, but are not required for
      bridging nor condensation. The conformational response following exposure to HU
      was investigated with a nanofluidic device that allows an in situ change in
      environmental solution conditions. The stretch of the nucleoprotein complex first
      increases, reaches an apex in ~20 min, and subsequently decreases to an
      equilibrium value pertaining to pre-incubated DNA molecules after ~2 h. This
      observation is rationalised in terms of a time-dependent bending rigidity by
      structural rearrangement of bound HU protein followed by compaction through
      bridging interaction. Results are discussed in regard to previous results
      obtained for nucleoid associated proteins H-NS and Hfq, with important
      implications for protein binding related gene regulation.

PMID- 29457178
TI  - Enantioselective aza-Friedel-Crafts reaction of cyclic ketimines with indoles
      using chiral imidazoline-phosphoric acid catalysts.
AB  - An enantioselective aza-Friedel Crafts reaction of cyclic 4-aryl-3-oxo-1,2,5
      thiadiazol-1,1-oxides as cyclic ketimines with indoles was developed. High
      enantioselectivities were observed for the reaction of various cyclic ketimines
      with indoles using chiral imidazoline-phosphoric acid catalysts. The obtained
      products can be converted to chiral alpha-amino amide and hydantoin.

PMID- 29457177
TI  - Unprecedented self-assembled architectures of surface-active ionic liquids in
      aqueous medium.
AB  - The formation of ultra-thin 2D crystalline nano-sheets, -spindles and -ribbons by
      self-assembly of benzimidazolium-based single-tailed surface active ionic liquids
      (SAILs) is observed for the first time. The nature of formed bilayer
      architectures is governed by the functionalization of alkyl chains of SAILs via
      an amide or ester moiety.

PMID- 29457179
TI  - An experimental and theoretical investigation of XPS and NEXAFS of 5-halouracils.
AB  - The C, N and O 1s excitation and ionization processes of 5X-uracil (X = F, Cl,
      Br, and I) were investigated using near edge X-ray absorption fine structure
      (NEXAFS) and X-ray photoemission (XPS) spectroscopies. This study aims at the
      fine assessment of the effects of the functionalization of uracil molecules by
      halogen atoms having different electronegativity and bound to the same molecular
      site. Two DFT-based approaches, which rely on different paradigms, have been used
      to simulate the experimental spectra and to assign the corresponding features.
      The analysis of the screening of the core holes of the different atoms via
      electronic charge density plots has turned out to be a useful tool to illustrate
      the competition between the partially aromatic and partially conjugate properties
      of this class of molecules.

PMID- 29457180
TI  - Multiscale design of ZnO nanostructured photocatalysts.
AB  - A systematic investigation of the photocatalytic activity (PCA) of nanostructured
      ZnO films showed how this is directly affected by the films' morphology at
      different scales, from the macroscale morphology of films (e.g. thickness and
      surface area), to the microscale feature arrangement (e.g. aligned vs. randomly
      oriented structures or interpenetrated ones), to the nanoscale structure (e.g.
      crystal size and orientation). The interest in immobilizing photocatalysts in
      water treatment stems from concerns about the potential toxicity of their slurry
      form, which requires expensive downstream removal. Immobilisation, though, leads
      to a reduction in PCA, generally attributed to a lower surface area. By reducing
      the films' feature size to the nanoscale, an immobilized photocatalyst with high
      surface area can be achieved. At this scale, however, feature structuring and
      morphology become important as they determine the interaction between light and
      the photocatalytic material. In this work, nanostructured ZnO films with
      different morphology, arrangement and structure were produced by electrochemical
      anodization of zinc and were tested using the degradation of phenol in a batch
      reactor as a model system. Results show that the PCA for immobilized catalysts
      can be optimised by controlling microscale arrangement (light absorbance
      capacity) and nanoscale structure (crystal size and orientation) rather than
      macroscale morphology (surface area). These results provide a clear direction to
      maximising the photocatalytic activity of immobilised photocatalysts for the
      removal of organic pollutants from water.

PMID- 29457181
TI  - Ab initio kinetics of the HOSO2 + 3O2 -> SO3 + HO2 reaction.
AB  - The detailed kinetic mechanism of the HOSO2 + 3O2 reaction, which plays a pivotal
      role in the atmospheric oxidation of SO2, was investigated using accurate
      electronic structure calculations and novel statistical thermodynamic/kinetic
      models. Explored using the accurate composite method W1U, the detailed potential
      energy surface (PES) revealed that the addition of O2 to a HOSO2 radical to form
      the adduct (HOSO4) proceeds via a transition state with a slightly positive
      barrier (i.e., 0.7 kcal mol-1 at 0 K). Such a finding compromises a long-term
      hypothesis about this channel of being a barrierless process. Moreover, the
      overall reaction was found to be slightly exothermic by 1.7 kcal mol-1 at 0 K,
      which is in good agreement with recent studies. On the newly-constructed PES, the
      temperature- and pressure-dependent behaviors of the title reaction were
      characterized in a wide range of conditions (T = 200-1000 K & P = 10-760 Torr)
      using the integrated deterministic and stochastic master equation/Rice-Ramsperger
      Kassel-Marcus (ME/RRKM) rate model in which corrections for hindered internal
      rotation (HIR) and tunneling treatments were included. The calculated numbers
      were found to be in excellent agreement with literature data. The sensitivity
      analyses on the derived rate coefficients with respect to the ab initio input
      parameters (i.e., barrier height and energy transfer) were also performed to
      further understand the kinetic behaviors of the title reaction. The detailed
      kinetic mechanism, consisting of thermodynamic and kinetic data (in NASA
      polynomial and modified Arrhenius formats, respectively), was also provided at
      different T & P for further use in the modeling/simulation of any related
      systems.

PMID- 29457182
TI  - 1,3-Iodo-amination of 2-methyl indoles via Csp2-Csp3 dual functionalization with
      iodine reagent.
AB  - A 1,3-iodo-amination with iodine reagent that involved the Csp2-Csp3 dual
      functionalization of 2-methyl indoles was developed to provide 2-aminomethyl-3
      iodo-indole derivatives. The iodo-amination proceeded via a 1,4-transfer of an
      imide group through the formation of an indolyl(phenyl)iodonium imide using
      PhI(OAc)2, followed by an iodination using DIH or a double iodination of indole
      using excess DIH.

PMID- 29457184
TI  - Photo-controlled fluorescence on/off switching of a pseudo[3]rotaxane between an
      AIE-active pillar[5]arene host and a photochromic bithienylethene guest.
AB  - A fluorescence photo-switch was constructed based on a host-guest
      pseudo[3]rotaxane between an AIE-active pillar[5]arene host bearing tetraphenyl
      ethylene moieties and a photo-responsive dithienylethylene guest containing two
      cyano-triazole branches. Its fluorescence on/off switching could be controlled by
      the photochromism reaction of the dithienylethylene unit.

PMID- 29457183
TI  - Diabatic potential energy surfaces of MgH2+ and dynamic studies for the Mg+(3p) +
      H2 -> MgH+ + H reaction.
AB  - The global diabatic potential energy surfaces (PESs) of the MgH2+ system, which
      can be used to study the dynamics of the Mg+(3p2P) + H2(X1Sigma) ->
      MgH+(X1Sigma+) + H(2S) reaction, are structured for the first time. The diabatic
      PESs are correlated with the ground state 12A' and the first excited state 22A'.
      The multi-reference configuration interaction method and the VQZ basis set are
      used in ab initio calculations, and diabatic potential energies are calculated
      based on the molecular properties of the dipole moment. The neural network method
      is applied to fit the matrix elements of the diabatic energy surfaces.
      Spectroscopic constants of H2(X1Sigmag+) and MgH+(X1Sigma+) obtained from the new
      PESs agree well with the experimental data. Based on the diabatic PESs of MgH2+,
      the time-dependent wavepacket calculations for the Mg+(3p2P) + H2(X1Sigmag+) ->
      MgH+(X1Sigma+) + H(2S) reaction are carried out to study the reaction dynamics.
      There is no threshold for this reaction because of the existence of barrierless
      reactive paths. The reaction has a high total integral cross section (ICS), and
      vibrationally resolved ICSs show an obvious population inversion of product
      vibrational states. The results of differential cross sections (DCSs) indicate
      that most product molecules tend to forward scatter.

PMID- 29457185
TI  - Effect of large deformation and surface stiffening on the transmission of a line
      load on a neo-Hookean half space.
AB  - A line force acting on a soft elastic solid, say due to the surface tension of a
      liquid drop, can cause significant deformation and the formation of a kink close
      to the point of force application. Analysis based on linearized elasticity theory
      shows that sufficiently close to its point of application, the force is borne
      entirely by the surface stress, not by the elasticity of the substrate; this
      local balance of three forces is called Neumann's triangle. However, it is not
      difficult to imagine realistic properties for which this force balance cannot be
      satisfied. For example, if the line force corresponds to surface tension of
      water, the numerical values of (unstretched) solid-vapor and solid-liquid surface
      stresses can easily be such that their sum is insufficient to balance the applied
      force. In such cases conventional (or naive) Neumann's triangle of surface forces
      must break down. Here we study how force balance is rescued from the breakdown of
      naive Neumann's triangle by a combination of (a) large hyperelastic deformations
      of the underlying bulk solid, and (b) increase in surface stress due to surface
      elasticity (surface stiffening). For a surface with constant surface stress (no
      surface stiffening), we show that the linearized theory remains accurate if the
      applied force is less than about 1.3 times the solid surface stress. For a
      surface in which the surface stress increases linearly with the surface stretch,
      we find that the Neumann's triangle construction works well as long as we replace
      the constant surface stress in the naive Neumann triangle by the actual surface
      stress underneath the line load.

PMID- 29457187
TI  - Allosteric regulation of metal-binding sites inside an optically-active helical
      foldamer and its tubular assemblies.
AB  - A helical foldamer possessing conformationally switchable metal-binding linkers
      underwent supramolecular polymerization to form a helical nanofiber. A reversible
      helix-to-helix transition of the helical nanofiber took place upon cooperative
      binding and release of Ag(i) ions via a metal-coordination-driven W-to-U-shape
      conformational change of the linkers in a positive allosteric manner.

PMID- 29457186
TI  - Recognition of shorter and longer trimethyllysine analogues by epigenetic reader
      proteins.
AB  - Histone Nepsilon-lysine methylation is a widespread posttranslational
      modification that is specifically recognised by a diverse class of Nepsilon
      methyllysine binding reader proteins. Combined thermodynamic data, molecular
      dynamics simulations, and quantum chemical studies reveal that reader proteins
      efficiently bind trimethylornithine and trimethylhomolysine, the simplest
      Nepsilon-trimethyllysine analogues that differ in the length of the side chain.

PMID- 29457188
TI  - Divergent synthesis of functionalized pyrrolidines and gamma-amino ketones via
      rhodium-catalyzed switchable reactions of vinyl aziridines and silyl enol ethers.
AB  - The control of reaction pathways for selective and enantiospecific synthesis of
      functionalized pyrrolidines and gamma-amino ketones has been realized. Rhodium
      catalyzed [3+2] cycloadditions of vinylaziridines and enolsilanes with a bulky
      silyl group gave functionalized pyrrolidines with moderate to excellent
      diastereoselectivities, while the reaction of silyl enol ethers with a less bulky
      silyl group afforded chiral gamma-amino ketones in good yields.

PMID- 29457189
TI  - Development of a Questionnaire to Assess Nursing Competencies for the Care of
      People with Psychiatric Disabilities in a Hospital Environment.
AB  - The recovery of people with psychiatric disabilities requires high-quality
      nursing care. However, the existing research on the nursing competencies needed
      for caring for people with psychiatric disabilities have been based on a narrow
      competency framework. By adopting a broader competency framework, this study
      aimed to find the competencies needed for the nursing care of people with
      psychiatric disabilities in a hospital environment. Accordingly, a questionnaire
      will be developed to measure these competences. First, a literature review and
      interviews with psychiatrists, psychiatric nurses, and people with psychiatric
      disabilities were conducted to develop the pool of competency items. Second, a
      pilot study was conducted to review the initial pool of items. Finally, a survey
      of 581 psychiatric nurses was used to conduct a series of principal component
      analyses to explore the structure of the questionnaire. The 17-item questionnaire
      included 5 factors, which accounted for 68.60% of the total variance: sense of
      responsibility, vocational identification, agreeableness, cooperation capacity,
      and carefulness; the Cronbach's alpha coefficients were 0.85, 0.85, 0.74, 0.80,
      and 0.77, respectively. Most of the competencies belonged to attitudes, values,
      and traits, which were overlooked in previous studies. The questionnaire has
      satisfactory internal reliability and structural validity, and could contribute
      some to the selection of the psychiatric workforce.

PMID- 29457190
TI  - Family-Based Interventions Targeting Improvements in Health and Family Outcomes
      of Children and Adolescents with Type 1 Diabetes: a Systematic Review.
AB  - PURPOSE OF REVIEW: A systematic review was conducted of family-based
      interventions to improve glycemic control, adherence, and psychosocial outcomes
      in children and adolescents with type 1 diabetes (T1D). Electronic databases were
      searched for randomized controlled trials (RCTs) published since the seminal
      Diabetes Control and Compliance Trial (DCCT). Interventions are summarized and
      findings reviewed to help guide clinical practice and future research. RECENT
      FINDINGS: Twenty-five RCTs are reviewed. The majority of studies (n = 15) focused
      on interventions targeting both children and adolescents and their caregivers and
      were delivered in diabetes clinics, outpatient settings, mental health clinics,
      or participants' homes. Family-based interventions for youth with T1D appear
      effective at improving diabetes and family-centered outcomes. Additional research
      is needed to examine the pathways to improvement in glycemic control, as outcomes
      were mixed. Future research should also involve measures beyond HbA1c given new
      markers for sustained health improvement and outcomes are being explored.

PMID- 29457191
TI  - Variation in intraocular pressure caused by repetitive positional changes during
      laparoscopic colorectal surgery: a prospective, randomized, controlled study
      comparing propofol and desflurane anesthesia.
AB  - Laparoscopic surgery is often prolonged and requires positional changes to
      facilitate surgical access. Previous studies reported intraocular pressure (IOP)
      changes in one fixed position. This study investigated the effect of desflurane
      and propofol anesthesia on IOP during repeated positional changes. A total of 46
      patients undergoing laparoscopic colorectal surgery were randomized into
      desflurane or propofol groups. IOP was measured using a handheld tonometer at
      seven time points: before induction (baseline), after endotracheal intubation,
      after pneumoperitoneum, after the first Trendelenburg and right tilt position,
      after reverse Trendelenburg and right tilt position, after the second
      Trendelenburg and right tilt position and before endotracheal extubation.
      Trendelenburg positioning raised IOP in both groups. In the desflurane group, IOP
      at the first Trendelenburg position was 6.27 and 8.48 mmHg higher than baseline
      IOP in left and right eye, respectively; IOP at the second Trendelenburg position
      was 7 and 9.44 mmHg higher than baseline in left and right eye, respectively. In
      the propofol group, IOP at the first Trendelenburg position was 2.04 and 4.04
      mmHg higher than baseline in left and right eyes, respectively. It was 3.04 and
      4.87 mmHg higher than baseline in left and right eye, respectively, at the second
      Trendelenburg position. In the desflurane group, 56.52% patients exhibited high
      IOP (>= 25 mmHg) compared with 13.04% in the propofol group at the second
      Trendelenburg position in the right eyes (P = 0.005). There was a positive
      correlation between IOP and peak inspiratory pressure (P < 0.001). Propofol
      anesthesia mitigated wide variations in IOP caused by repetitive positional
      changes during laparoscopic colorectal surgery.

PMID- 29457192
TI  - Influence of orthodontic appliance-derived artifacts on 3-T MRI movies.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has been used to study
      configurations of speech organs in the resting state. However, MRI is sensitive
      to metals, and numerous types of metallic appliances, most of which have a large
      magnetic susceptibility, are used in orthodontic treatment and may cause severe
      artifacts on MRI. We have developed techniques for obtaining MRI movies of the
      oral region, to evaluate articulatory changes, especially movement of the tongue,
      palate, and teeth, pre- and post-orthodontic/orthognathic treatment. We evaluated
      the influence of artifacts caused by orthodontic appliances, including fixed
      retainers, metal brackets, and wires, on measurements in 3-T MRI movies. METHODS:
      Sixteen healthy young adults (nine males, seven females; average age, 27 years)
      with normal occlusion were recruited. Four types of customized maxillary and
      mandibular plates were prepared by incorporating one of the following into the
      plate: (a) nothing, (b) a fixed canine-to-canine retainer, (c) metal brackets for
      the anterior and molar teeth, or (d) clear brackets for the anterior teeth and
      metal brackets for molars. A 3-T MRI movie, in segmented cine mode, was generated
      for each plate condition while participants pronounced a vowel-consonant-vowel
      syllable (/asa/). The size of the artifact due to the metallic brackets was
      measured. The face size and orthodontically important anatomical structures, such
      as the velum, the hard palate, and the laryngeal ventricle, were also measured.
      RESULTS: A large artifact was observed over the entire oral region around
      orthodontic appliances, altering regional visibility. The velopharyngeal height
      was measured as significantly longer in the presence of metal brackets. The
      maximum artifact size due to a metallic bracket was > 8 cm. Our results show that
      even if it is possible to obtain the measurements of palate length, nasion to
      sella, and nasion to basion in individuals wearing metal brackets for molars, the
      measurements might be affected due to the presence of artifacts. CONCLUSIONS:
      Orthodontic appliances, including metallic materials, sometimes produce
      significant measurement error in speech evaluation using MRI movies, which often
      become invisible or distorted by metallic orthodontic appliances. When the
      distorted image is measured, caution should be exercised, as the measurement may
      be affected. Based on the study, it is concluded that orthodontists should not
      necessarily remove all metallic appliances before MRI examination because the
      influence varies among the appliances and should also know that a significant
      measurement error in speech evaluation using MRI movie may occur by image
      distortion caused by metallic artifacts.

PMID- 29457193
TI  - Genome shuffling and ribosome engineering of Streptomyces virginiae for improved
      virginiamycin production.
AB  - The production of virginiamycin (VGM) from Streptomyces virginiae was improved by
      genome shuffling and ribosome engineering companied with a high-throughput
      screening method integrating deep-well cultivation and the cylinder-plate
      detecting. First, a novel high-throughput method was developed to rapidly screen
      large numbers of VGM-producing mutants. Then, the starting population of genome
      shuffling was obtained through ultraviolet (UV) and microwave mutagenesis, and
      four mutants with higher productivity of VGM were selected for genome shuffling.
      Next, the parent protoplasts were inactivated by UV and heat when a fusant
      probability was about 98%. Streptomycin resistance was used as an evolutionary
      pressure to extend positive effects on VGM synthesis. Finally, after five rounds
      of genome shuffling, a genetically stable strain G5-103 was obtained and
      characterized to be able to yield 251 mg/L VGM, which was 3.1- and 11.6-fold
      higher than that of the mutant strain UV 1150 and the wild-type strain,
      respectively.

PMID- 29457194
TI  - Reproduction in woody perennial Citrus: an update on nucellar embryony and self
      incompatibility.
AB  - KEY MESSAGE: Review on citrus reproduction. Citrus is one of the most important
      and widely grown fruit crops. It possesses several special reproductive
      characteristics, such as nucellar embryony and self-incompatibility. The special
      phenomenon of nucellar embryony in citrus, also known as the polyembryony, is a
      kind of sporophytic apomixis. During the past decade, the emergence of novel
      technologies and the construction of multiple citrus reference genomes have
      facilitated rapid advances to our understanding of nucellar embryony. Indeed,
      several research teams have preliminarily determined the genetic basis of citrus
      apomixis. On the other hand, the phenomenon of self-incompatibility that promotes
      genetic diversity by rejecting self-pollen and accepting non-self-pollen is
      difficult to study in citrus because the long juvenile period of citrus presents
      challenges to identifying candidate genes that control this phenomenon. In this
      review, we focus on advances to our understanding of reproduction in citrus from
      the last decade and discuss priorities for the coming decade.

PMID- 29457195
TI  - The association between mood state and chronobiological characteristics in
      bipolar I disorder: a naturalistic, variable cluster analysis-based study.
AB  - BACKGROUND: Multiple types of chronobiological disturbances have been reported in
      bipolar disorder, including characteristics associated with general activity
      levels, sleep, and rhythmicity. Previous studies have focused on examining the
      individual relationships between affective state and chronobiological
      characteristics. The aim of this study was to conduct a variable cluster analysis
      in order to ascertain how mood states are associated with chronobiological traits
      in bipolar I disorder (BDI). We hypothesized that manic symptomatology would be
      associated with disturbances of rhythm. RESULTS: Variable cluster analysis
      identified five chronobiological clusters in 105 BDI subjects. Cluster 1,
      comprising subjective sleep quality was associated with both mania and
      depression. Cluster 2, which comprised variables describing the degree of
      rhythmicity, was associated with mania. Significant associations between mood
      state and cluster analysis-identified chronobiological variables were noted.
      Disturbances of mood were associated with subjectively assessed sleep
      disturbances as opposed to objectively determined, actigraphy-based sleep
      variables. No associations with general activity variables were noted.
      Relationships between gender and medication classes in use and cluster analysis
      identified chronobiological characteristics were noted. Exploratory analyses
      noted that medication class had a larger impact on these relationships than the
      number of psychiatric medications in use. CONCLUSIONS: In a BDI sample, variable
      cluster analysis was able to group related chronobiological variables. The
      results support our primary hypothesis that mood state, particularly mania, is
      associated with chronobiological disturbances. Further research is required in
      order to define these relationships and to determine the directionality of the
      associations between mood state and chronobiological characteristics.

PMID- 29457196
TI  - The Landscape of Diabetic Kidney Disease in the United States.
AB  - PURPOSE OF REVIEW: The purposes of this review are to identify population
      characteristics of important risk factors for the development and progression of
      diabetic kidney disease (DKD) in the United States and to discuss barriers and
      opportunities to improve awareness, management, and outcomes in patients with
      DKD. RECENT FINDINGS: The major risk factors for the development and progression
      of DKD include hyperglycemia, hypertension, and albuminuria. DKD
      disproportionately affects minorities and individuals with low educational and
      socioeconomic status. Barriers to effective management of DKD include the
      following: (a) limited patient and healthcare provider awareness of DKD, (b) lack
      of timely referrals of patients to a nephrologist, (c) low patient healthcare
      literacy, and (d) insufficient access to healthcare and health insurance.
      Increased patient and physician awareness of DKD has been shown to enhance
      patient outcomes. Multifactorial and multidisciplinary interventions targeting
      multiple risk factors and patient/physician education may provide better outcomes
      in patients with DKD.

PMID- 29457197
TI  - Inactivation of the indole-diterpene biosynthetic gene cluster of Claviceps
      paspali by Agrobacterium-mediated gene replacement.
AB  - The hypocrealean fungus Claviceps paspali is a parasite of wild grasses. This
      fungus is widely utilized in the pharmaceutical industry for the manufacture of
      ergot alkaloids, but also produces tremorgenic and neurotoxic indole-diterpene
      (IDT) secondary metabolites such as paspalitrems A and B. IDTs cause significant
      losses in agriculture and represent health hazards that threaten food security.
      Conversely, IDTs may also be utilized as lead compounds for pharmaceutical drug
      discovery. Current protoplast-mediated transformation protocols of C. paspali are
      inadequate as they suffer from inefficiencies in protoplast regeneration, a low
      frequency of DNA integration, and a low mitotic stability of the nascent
      transformants. We adapted and optimized Agrobacterium tumefaciens-mediated
      transformation (ATMT) for C. paspali and validated this method with the
      straightforward creation of a mutant strain of this fungus featuring a targeted
      replacement of key genes in the putative IDT biosynthetic gene cluster. Complete
      abrogation of IDT production in isolates of the mutant strain proved the
      predicted involvement of the target genes in the biosynthesis of IDTs. The mutant
      isolates continued to produce ergot alkaloids undisturbed, indicating that
      equivalent mutants generated in industrial ergot producers may have a better
      safety profile as they are devoid of IDT-type mycotoxins. Meanwhile, ATMT
      optimized for Claviceps spp. may open the door for the facile genetic engineering
      of these industrially and ecologically important organisms.

PMID- 29457199
TI  - The genetic self.

PMID- 29457198
TI  - Recent advances in synthetic methods and applications of silver nanostructures.
AB  - As the advanced functional materials, silver nanoparticles are potentially useful
      in various fields such as photoelectric, bio-sensing, catalysis, antibacterial
      and other fields, which are mainly based on their various properties. However,
      the properties of silver nanoparticles are usually determined by their size,
      shape, and surrounding medium, which can be modulated by various synthesis
      methods. In this review, the fabrication methods for synthesizing silver
      nanoparticles of different shapes and specific size are illustrated in detail.
      Besides, the corresponding properties and applications of silver nanoparticles
      are also discussed in this paper.

PMID- 29457201
TI  - Validity of oral fluid test for Delta-9-tetrahydrocannabinol in drivers using the
      2013 National Roadside Survey Data.
AB  - BACKGROUND: Driving under the influence of marijuana is a serious traffic safety
      concern in the United States. Delta 9-tetrahydrocannabinol (THC) is the main
      active compound in marijuana. Although blood THC testing is a more accurate
      measure of THC-induced impairment, measuring THC in oral fluid is a less
      intrusive and less costly method of testing. METHODS: We examined whether the
      oral fluid THC test can be used as a valid alternative to the blood THC test
      using a sensitivity and specificity analysis and a logistic regression, and
      estimate the quantitative relationship between oral fluid THC concentration and
      blood THC concentration using a correlation analysis and a linear regression on
      the log-transformed THC concentrations. We used data from 4596 drivers who
      participated in the 2013 National Roadside Survey of Alcohol and Drug Use by
      Drivers and for whom THC testing results from both oral fluid and whole blood
      samples were available. RESULTS: Overall, 8.9% and 9.4% of the participants
      tested positive for THC in oral fluid and whole blood samples, respectively.
      Using blood test as the reference criterion, oral fluid test for THC positivity
      showed a sensitivity of 79.4% (95% CI: 75.2%, 83.1%) and a specificity of 98.3%
      (95% CI: 97.9%, 98.7%). The log-transformed oral fluid THC concentration
      accounted for about 29% of the variation in the log-transformed blood THC
      concentration. That is, there is still 71% of the variation in the log
      transformed blood THC concentration unexplained by the log-transformed oral fluid
      THC concentration. Back-transforming to the original scale, we estimated that
      each 10% increase in the oral fluid THC concentration was associated with a 2.4%
      (95% CI: 2.1%, 2.8%) increase in the blood THC concentration. CONCLUSIONS: The
      oral fluid test is a highly valid method for detecting the presence of THC in the
      blood but cannot be used to accurately measure the blood THC concentration.

PMID- 29457200
TI  - Network-Based Research on Rural Opioid Use: an Overview of Methods and Lessons
      Learned.
AB  - PURPOSE OF REVIEW: The purpose of this paper is to provide a thorough overview of
      methods used for recruitment, network data collection, and network data
      management in a network-based study of rural people who use drugs (PWUD) and to
      offer methodological recommendations for future research on rural drug use.
      RECENT FINDINGS: The Social Networks among Appalachian People (SNAP) study
      recruited a cohort of 503 rural PWUD via respondent-driven sampling (RDS) and has
      retained more than 80% of eligible participants over 7-9 years. SNAP has yielded
      important methodological insights, including that (1) RDS referral was non-random
      and disproportionately involved kin and (2) interviewer-administered
      questionnaires were successful in eliciting accurate name and age information
      about network members. The SNAP experience suggests that RDS was a successful
      recruitment strategy for rural PWUD and questionnaires administered by community
      based interviewers in the context of a Certificate of Confidentiality could
      elicit detailed data on PWUD risk networks.

PMID- 29457202
TI  - Three new coccidians (Cyclospora, Eimeria) from eastern moles, Scalopus aquaticus
      (Linnaeus) (Mammalia: Soricomorpha: Talpidae) from Arkansas, USA.
AB  - Three new species of coccidians (Apicomplexa: Eimeriidae) are described from
      eastern moles, Scalopus aquaticus (Linnaeus) from Arkansas. Oocysts of Cyclospora
      duszynskii n. sp. are subspheroidal with a smooth bi-layered wall, measure 11.4 *
      10.0 um, and have a length/width (L/W) ratio of 1.1; both micropyle and oocyst
      residuum are absent, but a single polar granule is present. Sporocysts are
      ellipsoidal and measure 7.2 * 5.4 um, L/W 1.3; an indistinct Stieda body is
      present, but the sub-Stieda and para-Stieda bodies are absent and the sporocyst
      residuum is composed of medium to large granules of different sizes along the
      edge of the sporocyst. Oocysts of Cyclospora yatesi n. sp. are subspheroidal to
      ovoidal with an ornate outer wall, measure 17.0 * 15.2 um, L/W 1.1; both
      micropyle and oocyst residuum are absent, but a single polar granule is present.
      Sporocysts are ellipsoidal and measure 9.7 * 7.3 um, L/W 1.3; an indistinct
      Stieda body is present, but sub-Stieda and para-Stieda bodies are absent and the
      sporocyst residuum is composed of medium to large granules of different sizes
      along the edge of the sporocyst. Oocysts of Eimeria paulettefordae n. sp. are
      ovoidal to ellipsoidal with an ornate outer wall, measure 30.0 * 25.4 um, L/W
      1.2; both micropyle and oocyst residuum are absent, but a single polar granule is
      present. Sporocysts are ellipsoidal and measure 12.6 * 9.2 um, L/W 1.4; a button
      like Stieda body is present, but sub-Stieda and para-Stieda bodies are absent and
      the sporocyst residuum is composed of medium to large granules of different sizes
      along the edge of the sporocyst. These are the first coccidians described from
      Arkansas populations of S. aquaticus. In addition, a summary is provided on the
      cyclosporans and eimerians from North American talpids.

PMID- 29457203
TI  - Challenges and Opportunities in Establishing and Maintaining Newborn Screening in
      a Rural Area of Andhra Pradesh - Task Force Study by Indian Council of Medical
      Research.
AB  - OBJECTIVE: The primary objective was to evaluate the feasibility of setting up
      newborn screening in rural areas in India. Secondary objective was to enhance the
      knowledge and awareness towards early detection of diseases by newborn screening,
      management of the affected baby and to impart genetic counseling. METHODS:
      Awareness programs were conducted at different mandals in the district for the
      medical practioners during the preparatory phase of the Task Force Project.
      Educative lectures and clinical meetings regarding the importance and relevance
      of newborn screening were held every 3 months initially and half yearly later.
      Families were counselled during antenatal check-ups. RESULTS: Good co-operation
      was obtained from medical doctors and their willingness to participate in sample
      collection from the hospitals. Families accepted screening after an initial
      period of resistance. The fact that screening of this kind will help their babies
      made a positive impact. Many families started promoting newborn screening to
      their friends and relations. Confirmation of diagnosis, treatment, and follow-up
      were satisfactory with almost negligible number of cases lost to follow-up.
      CONCLUSIONS: With proper planning and commitment on the part of health
      authorities, it is possible to implement newborn screening in rural areas in
      India as well.

PMID- 29457204
TI  - Prevention and Management of Childhood Obesity.
AB  - Childhood obesity has been recognized as a global pandemic. Preventive strategies
      have proven to be the most effective public health intervention in curbing this
      pandemic. A multi-component approach involving dietary modification and advocacy
      for a healthy lifestyle comprising of regular physical activity, minimizing
      screen time and behavioral interventions have been found beneficial in preventing
      obesity. A life-cycle approach has been recommended where preventive
      interventions go as far back as affecting maternal, fetal and early childhood
      nutrition and lifestyle. Family, school and community involvement is important
      for long term results, so is the involvement of government in developing policies
      that help create an environment and opportunities for healthy diet and physical
      activity. Management of childhood obesity is challenging. It involves following a
      structured weight reduction programme individualized for every child, along with
      adoption of a healthy diet and life style. Anti-obesity drugs have a limited role
      in childhood years and are not recommended in younger children. Bariatric surgery
      is reserved for morbidly obese older adolescents but its long term safety data is
      limited in this age group.

PMID- 29457205
TI  - Growth Hormone Therapy and Lipid Profile.

PMID- 29457206
TI  - CPAP with Resuscitation Mask in a Neonate with Cleft Lip and Cleft Palate.

PMID- 29457207
TI  - Pediatric Endocrinology in India: Development, Progress, Problems and Challenges.
AB  - The exponential growth of biological sciences and biotechnology has promoted the
      development of subspecialties / super specialties in medicine. In developing
      countries, socioeconomic factors influence and determine competing health
      priorities, often delaying the development of subspecialties in medicine. Tracing
      the history of development and progress of Endocrinology in general and Pediatric
      Endocrinology in particular, provides an overall perspective of the problems and
      challenges which lie ahead.

PMID- 29457208
TI  - Children Deserve Smoke Free World.
AB  - Tobacco smoke, active or passive exposure was the major cause of preventable
      morbidity and mortality in the world during twentieth century and will continue
      to be the same in the twenty-first century also if the current trends continue.
      Both active and passive smoking are having significance in relation to child
      health. Exposure starts antenatally from placenta to the fetus and later phases
      through passive exposure to experimental and regular smoking and ultimately
      addiction and habitual smoking. Evidences are in favour of causal relationship
      with intrauterine growth restriction, sudden infant death syndrome, decreased
      pulmonary function, increased risk for respiratory tract infection, otitis media,
      wheeze, asthma, neurobehavioral disorders, cleft palate and triggering
      pathogenesis of fetal and childhood onset of adult diseases, especially pulmonary
      and cardio vascular diseases. All these facts stress the importance of behavioral
      changes in the population as well as stringent public health measures and
      legislation for ensuring smoke free work places, public places and households for
      children. M POWER- Package by WHO is a novel global initiative taking us closer
      to the target of achieving tobacco free environment for children in the near
      future.

PMID- 29457209
TI  - Agreement Between Integrated Management of Childhood Illness and Final Diagnosis
      in Acute Respiratory Tract Infections.
AB  - OBJECTIVE: To evaluate the agreement between integrated management of childhood
      illness (IMCI) and final diagnosis in patients presenting with cough at the
      second and third level health institutions. METHODS: This cross-sectional study
      included 373 children aged 2-60 mo who presented with cough at the pediatric
      emergency and outpatient clinics in the Department of Pediatrics. After clinical
      examination of children, body temperature, respiratory rate, saturation, presence
      or absence of the chest indrawing, rales, wheezing and laryngeal stridor were
      recorded. Cases were categorized according to IMCI algorithm regarding the
      severity using the color code, such as red (urgent treatment), yellow (treatment
      in the hospital), or green (treatment at home). Final diagnosis after physical
      examination, laboratory analysis and chest X-ray was compared with the IMCI
      algorithm. RESULTS: Study agreement between IMCI classification and final
      diagnosis was 74.3% with kappa value 0.55 (moderate agreement). Similar agreement
      values were detected in both the second and third level health institutions.
      Health condition and gender did not affect agreement value. Agreement were found
      to be high in patients <24 mo of age (K = 0.67), presence of fever and cough (K =
      0.54), tachypnea (K = 0.93), chest indrawing (K = 1.00) and oxygen saturation of
      <94%(K = 0.90). CONCLUSIONS: Adding saturation level to the IMCI algorithmic
      diagnosis may increase agreement between IMCI classification and final diagnosis.

PMID- 29457212
TI  - A Case of Alpha-Fetoprotein-Producing Adenocarcinoma of the Esophagogastric
      Junction in which Long-Term Survival Was Achieved by Means of Individualized
      Multidisciplinary Therapy.

PMID- 29457210
TI  - Hospital Cirrhosis Volume and Readmission in Patients with Cirrhosis in
      California.
AB  - BACKGROUND: Patients with cirrhosis are at high readmission risk. Using a large
      statewide database, we evaluated the effect of hospital cirrhosis-related patient
      volume on 30-day readmissions in patients with cirrhosis. METHODS: We conducted a
      retrospective study of the Healthcare Cost and Utilization Project State
      Inpatient Database for adult patients with cirrhosis, as defined by International
      Classification of Diseases, Ninth Revision (ICD-9) codes, hospitalized in
      California between 2009 and 2011. Multivariable logistic regression analysis was
      performed to evaluate the effect of hospital volume on 30-day readmissions.
      RESULTS: A total of 69,612 patients with cirrhosis were identified in 405
      hospitals; 24,062 patients were discharged from the top 10% of hospitals (N = 41)
      by cirrhosis volume, and 45,550 patients in the bottom 90% (N = 364). Compared
      with higher-volume centers, lower-volume hospitals cared for patients with
      similar average Quan-Charlson-Deyo (QCD) comorbidity scores (6.54 vs. 6.68),
      similar proportion of hepatitis B and fatty liver disease, lower proportion of
      hepatitis C (34.8 vs. 41.5%) but greater proportion of alcoholic liver disease
      (53.1 vs. 47.4%). Multivariable logistic regression analysis demonstrated
      admission to a lower-volume hospital did not predict 30-day readmission (odds
      ratio [OR] 0.97, 95% confidence interval [CI] 0.92-1.01) after adjusting for
      sociodemographics, QCD score, cirrhosis severity, and hospital characteristics.
      Instead, liver transplant center status significantly decreased the risk of
      readmission (OR 0.87, 95% CI 0.80-0.94). Ascites, hepatic encephalopathy,
      hepatocellular carcinoma, higher QCD, and presence of alcoholic liver disease and
      hepatitis C were also independent predictors. CONCLUSIONS: Readmissions within 30
      days were common among patients with cirrhosis hospitalized in California. While
      hospital cirrhosis volume did not predict 30-day readmissions, liver transplant
      center status was protective of readmissions. Medically complicated patients with
      cirrhosis at hospitals without liver transplant centers may benefit from
      additional support to prevent readmission.

PMID- 29457211
TI  - Acetarsol Suppositories: Effective Treatment for Refractory Proctitis in a Cohort
      of Patients with Inflammatory Bowel Disease.
AB  - BACKGROUND: Management of proctitis refractory to conventional therapies presents
      a common clinical problem. The use of acetarsol suppositories, which are derived
      from organic arsenic, was first described in 1965. Data concerning clinical
      efficacy and tolerability are very limited. AIM: To examine the efficacy of
      acetarsol suppositories for the treatment of refractory proctitis. METHODS: A
      retrospective analysis was performed on patients with inflammatory bowel disease
      treated with acetarsol suppositories between 2008 and 2014 at Addenbrooke's
      Hospital, Cambridge, United Kingdom. Clinical response was defined as resolution
      of symptoms back to baseline at the time of next clinic review. RESULTS: Thirty
      nine patients were prescribed acetarsol suppositories between March 2008 and July
      2014 (29 patients with ulcerative colitis, nine with Crohn's disease, and one
      with indeterminate colitis). Thirty-eight were included for analysis. The
      standard dose of acetarsol was 250 mg twice daily per rectum for 4 weeks.
      Clinical response was observed in 26 patients (68%). Of the 11 patients who had
      endoscopic assessment before and after treatment, nine (82%) showed endoscopic
      improvement and five (45%) were in complete remission (Wilcoxon signed-rank test
      p = 0.006). One patient developed a macular skin rash 1 week after commencing
      acetarsol, which resolved within 4 weeks of drug cessation. CONCLUSION: Acetarsol
      was effective for two out of every three patients with refractory proctitis. This
      cohort had failed a broad range of topical and systemic treatments, including
      anti-TNFalpha therapy. Clinical efficacy was reflected in significant endoscopic
      improvement. Adverse effects of acetarsol were rare.

PMID- 29457213
TI  - Trends in diagnosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in
      India: A report of multicenter data from a web-based registry.
AB  - INTRODUCTION: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare
      tumors. We report data of 407 GEP-NET cases from a neuroendocrine tumor (NET)
      registry in India. METHODS: The AP-NET registry is an open-label, multicenter,
      longitudinal observational registry of patients with GEP-NETs in which six
      tertiary care oncology centers contributed data. Data was prospectively entered
      in a dedicated computerized database and was reviewed retrospectively. The
      patients were divided into three cohorts-those diagnosed from 2001 to 2005, from
      2006 to 2010, and from 2011 to 2016. RESULTS: Of the 407 cases registered, 37
      were in Cohort I, 136 in Cohort II, and 234 in Cohort III. Majority were
      symptomatic with only 98 patients (24.0%) asymptomatic. The most common
      presentation of non-functional tumors was abdominal pain (42.4%), while
      functional tumors presented most commonly with carcinoid syndrome. Use of DOTA
      PET, introduced in 2011, has increased evaluation in 33.3% patients in Cohort
      III. The most common primary site was pancreas in all three cohorts. Male
      preponderance (58.3%) was seen. Histopathological grading was obtained in 230
      (56.5%) patients-118 (29%) Grade I, 74 (18.2%) Grade II, and 36 (8.8%) Grade III
      NET. CONCLUSION: This report highlights changing trends in the diagnosis and
      reporting of NETs over the last 15 years.

PMID- 29457215
TI  - The effect of anaesthetic technique during primary breast cancer surgery on
      neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and return to intended
      oncological therapy.
AB  - Inflammation and immunosuppression contribute to the pathogenesis of cancer. An
      increased neutrophil-lymphocyte ratio reflects these processes and is associated
      with adverse cancer outcomes. Whether anaesthetic technique for breast cancer
      surgery influences these factors, and potentially cancer recurrence, remains
      unknown. We conducted a secondary analysis in patients enrolled in an ongoing
      trial of anaesthetic technique on breast cancer recurrence. The primary
      hypothesis was that postoperative neutrophil-lymphocyte ratio is lower in
      patients allocated to receive propofol-paravertebral rather than inhalational
      agent-opioid anaesthesia for primary breast cancer surgery. Among 397 patients,
      116 had differential white cell counts performed pre-operatively and
      postoperatively. Pre-operative neutrophil-lymphocyte ratio was similar in the
      propofol-paravertebral 2.3 (95%CI 1.8-2.8) and inhalational agent-opioid
      anaesthesia 2.2 (1.9-3.2) groups, p = 0.72. Postoperative neutrophil-lymphocyte
      ratio was lower (3.0 (2.4-4.2) vs. 4.0 (2.9-5.4), p = 0.001) in the propofol
      paravertebral group. Propofol-paravertebral anaesthesia attenuated the
      postoperative increase in the neutrophil-lymphocyte ratio.

PMID- 29457214
TI  - Maintenance zinc therapy after initial penicillamine chelation to treat
      symptomatic hepatic Wilson's disease in resource constrained setting.
AB  - BACKGROUND: Experience with zinc in treating symptomatic hepatic Wilson's disease
      (WD) is limited. AIM: To study the efficacy of Penicillamine followed by zinc in
      treating symptomatic hepatic Wilson's disease. METHODS: We retrospectively
      analyzed case records of 31 symptomatic hepatic WD patients for whom disease
      severity scores (Child's, model for end-stage liver disease (MELD), Nazer's, and
      New Wilson Index (NWI) score) and 24-h urinary copper were compared at 3-time
      points-baseline at presentation, at transition from penicillamine to zinc and at
      end of follow up. RESULTS: Thirty-one patients (median age 11 [5-24] years) with
      symptomatic hepatic WD were studied; ten had associated neuropsychiatric
      manifestations of WD. Penicillamine was changed to zinc sulfate either due to
      financial constraints (28 patients) or due to adverse effects of penicillamine (3
      patients). At presentation (baseline), six patients belonged to Child's class A,
      five to Child's B, and 17 to Child's C. Duration of initial penicillamine
      chelation therapy was 134 (2-320) weeks, and of subsequent zinc therapy was 363
      (35-728) weeks. There was a significant improvement in liver function tests and
      disease severity scores (Child's, MELD, Nazer's, and NWI score) at the transition
      from penicillamine to zinc compared to baseline. This improvement was maintained
      until the end of study period with 90% survival at 10 (2-20) years. Fifteen of
      the 17 Child's C cirrhotic patients showed significant improvement in disease
      severity scores from baseline until end of follow up. CONCLUSIONS: Penicillamine
      followed by zinc may be a safe and effective treatment in resource-constrained
      setting for symptomatic hepatic WD patients in all grades of baseline disease
      severity. Some patients with decompensated cirrhosis due to WD may be managed
      with medical treatment, avoiding liver transplantation.

PMID- 29457216
TI  - N-acetylcysteine for major mental disorders: a systematic review and meta
      analysis of randomized controlled trials.
AB  - OBJECTIVE: This systematic review and meta-analysis of randomized controlled
      trials (RCTs) examined the efficacy and safety of adjunctive N-acetylcysteine
      (NAC), an antioxidant drug, in treating major depressive disorder (MDD), bipolar
      disorder, and schizophrenia. METHODS: The PubMed, Cochrane Library, PsycINFO,
      CNKI, CBM, and WanFang databases were independently searched and screened by two
      researchers. Standardized mean differences (SMDs), risk ratios, and their 95%
      confidence intervals (CIs) were computed. RESULTS: Six RCTs (n = 701) of NAC for
      schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and
      MDD (one RCT, n = 269) were identified and analyzed as separate groups.
      Adjunctive NAC significantly improved total psychopathology (SMD = -0.74, 95% CI:
      -1.43, -0.06; I2 = 84%, P = 0.03) in schizophrenia, but it had no significant
      effect on depressive and manic symptoms as assessed by the Young Mania Rating
      Scale in bipolar disorder and only a small effect on major depressive symptoms.
      Adverse drug reactions to NAC and discontinuation rates between the NAC and
      control groups were similar across the three disorders. CONCLUSIONS: Adjunctive
      NAC appears to be a safe treatment that has efficacy for schizophrenia, but not
      for bipolar disorder or MDD. Further higher quality RCTs are warranted to
      determine the role of adjunctive NAC in the treatment of major psychiatric
      disorders.

PMID- 29457217
TI  - Getting a Read on Ready To Learn Media: A Meta-analytic Review of Effects on
      Literacy.
AB  - Most U.S. preschoolers have consumed media created with funding from the U.S.
      Department of Education's Ready To Learn (RTL) initiative, which was established
      to promote school readiness among children ages 2-8. Synthesizing data from 45
      evaluations (N = 24,624 unique child participants), this meta-analysis examined
      the effects of RTL media exposure on young children's literacy skills. Results
      indicate positive effects of RTL media exposure on children's literacy outcomes,
      especially vocabulary and phonological concepts. These effects are equivalent to
      about one-and-a-half months of literacy learning above and beyond typical growth.
      Findings are robust across a variety of research designs and for exposure to both
      television and new media. These results are discussed in terms of accountability
      evidence for RTL and larger debates in scholarly understanding of educational
      media effects.

PMID- 29457218
TI  - Regulatory T cells are required for normal and activin-promoted wound repair in
      mice.
AB  - Healing of skin wounds is orchestrated by various types of immune cells, but
      little is known about the role of FoxP3+ regulatory T cells (Tregs) in this
      process. Here, we determined if Tregs are important for wound healing in normal
      mice and if they contribute to the accelerated healing of mice overexpressing the
      growth and differentiation factor activin. Diphtheria toxin induced Treg
      depletion prior to injury caused impaired healing characterized by delayed
      reepithelialization, reduced wound contraction, and impaired vessel maturation.
      The accelerated wound repair of activin-transgenic mice was also abrogated.
      Mechanistically, we found a strong increase in IL-4 levels combined with
      overrepresentation of T-bet+ and GATA-3+ alphabeta T cells in Treg-depleted 7-day
      wounds. In addition, numbers of IFN-gamma- or IL-17A-producing CD4+ and CD4- T
      cells were elevated. These results demonstrate that Treg depletion in wounds
      facilitates the expansion of an alphabeta T-cell population with features of Th1
      and Th2 cells, and suggest that concomitant changes in the cytokine milieu
      disturb the healing process.

PMID- 29457219
TI  - Smokin' hot: adolescent smoking and the risk of psychosis.
AB  - OBJECTIVE: Daily smoking has been associated with a greater risk of psychosis.
      However, we are still lacking studies to adjust for baseline psychotic
      experiences and other substance use. We examined associations between daily
      smoking and psychosis risk in a 15-year follow-up while accounting for these
      covariates in a prospective sample (N = 6081) from the Northern Finland Birth
      Cohort 1986. METHODS: Self-report questionnaires on psychotic experiences (PROD
      screen), tobacco smoking and other substance use were completed when the cohort
      members were 15-16 years old. Tobacco smoking was categorized into three groups
      (non-smokers, 1-9 cigarettes and >=10 cigarettes/day). Psychosis diagnoses were
      obtained from national registers until the age of 30 years. RESULTS: Subjects in
      heaviest smoking category were at increased risk of subsequent psychosis
      (unadjusted HR = 3.15; 95% CI 1.94-5.13). When adjusted for baseline psychotic
      experiences the association persisted (HR = 2.87; 1.76-4.68) and remained
      significant even after adjustments for multiple known risk factors such as
      cannabis use, frequent alcohol use, other illicit substance use, parental
      substance abuse, and psychosis. Furthermore, number of smoked cigarettes
      increased psychosis risk in a dose-response manner (adjusted OR = 1.05; 1.01
      1.08). CONCLUSION: Heavy tobacco smoking in adolescence was associated with a
      greater risk for psychosis even after adjustment for confounders.

PMID- 29457220
TI  - Event-related potentials of emotional and neutral memories: The role of encoding
      position and delayed testing.
AB  - Previous research found that memory is not only better for emotional information
      but also for neutral information that has been encoded in the context of an
      emotional event. In the present ERP study, we investigated two factors that may
      influence memory for neutral and emotional items: temporal proximity between
      emotional and neutral items during encoding, and retention interval (immediate
      vs. delayed). Forty-nine female participants incidentally encoded 36 unpleasant
      and 108 neutral pictures (36 neutral pictures preceded an unpleasant picture, 36
      followed an unpleasant picture, and 36 neutral pictures were preceded and
      followed by neutral pictures) and participated in a recognition memory task
      either immediately (N = 24) or 1 week (N = 25) after encoding. Results showed
      better memory for emotional pictures relative to neutral pictures. In accordance,
      enhanced centroparietal old/new differences (500-900 ms) during recognition were
      observed for unpleasant compared to neutral pictures, most pronounced for the 1
      week interval. Picture position effects, however, were only subtle. During
      encoding, late positive potentials for neutral pictures were slightly lower for
      neutral pictures following unpleasant ones, but only at trend level. To
      summarize, we could replicate and extend previous ERP findings showing that
      emotionally arousing events are better recollected than neutral events,
      particularly when memory is tested after longer retention intervals. Picture
      position during encoding, however, had only small effects on elaborative
      processing and no effects on memory retrieval.

PMID- 29457221
TI  - Association of STAT6 gene variants with food allergy diagnosed by double-blind
      placebo-controlled food challenges.
AB  - This study describes the role of two STAT6 gene variants in food allergy using
      data of patients and their parents who underwent double-blind placebo-controlled
      food challenges (DBPCFCs). After quality control, 369 trios were analysed
      including 262 children (71.0%) with food allergy. Associations were tested by the
      Family based association test. The A alleles of both SNPs were associated with
      food allergy (P = .036 and P = .013 for rs324015 and rs1059513, respectively).
      Furthermore, these A alleles were associated with peanut allergy, higher sIgE
      levels to both peanut and cow's milk, more severe symptoms and higher eliciting
      doses during peanut and cow's milk DBPCFCs (all P < .05). In silico analysis
      indicates that the identified risk variants increase STAT6 expression which
      stimulates the differentiation of CD4 +  T cells to the Th2 subset. In
      conclusion, STAT6 variants may be involved in the pathophysiology of food allergy
      and their role seems to be independent of the allergenic food.

PMID- 29457222
TI  - Extreme dentition does not prevent diet and tooth diversification within
      combtooth blennies (Ovalentaria: Blenniidae).
AB  - The dentition of fishes can be quite striking and is often correlated with a
      specific diet. Combtooth blennies have long incisiform oral teeth, unlike most
      actinopterygians. It has been suggested that the long tooth morphology is an
      adaptation for detritivory, but given the diversity of diets (detritus, coral
      polyps, polychaetes, and pieces of other fishes), are blenny teeth indeed
      monomorphic? Or does tooth variation associated with diet still exist at this
      extreme? To explore tooth and diet diversification, we used a new phylogenetic
      hypothesis of Blenniidae, measured tooth shape, number, and mode of attachment,
      and quantified blenniid diet. The ancestral diet of blennies contained detritus
      and diversified into many different diets, including almost exclusively
      detritivory. Our results reveal a dental cline that may be constrained by tooth
      shape, but has not prevented diet diversification. Ancestral state reconstruction
      of tooth morphologies suggests that the ancestor of blennies had many unattached
      teeth and featured transitions to fewer attached teeth, with several transitions
      back to attached or unattached teeth. The dentition of blenniids is not
      monotypic; rather it is diverse and small changes in tooth shape are accompanied
      by changes in size, number, attachment, and often diet.

PMID- 29457223
TI  - Programming repercussions of early life training exercise on the heart.

PMID- 29457224
TI  - Factors associated with nutritional status and dietary practices of Bangladeshi
      adolescents in early pregnancy.
AB  - Bangladesh has a high prevalence of adolescent pregnancy, but little is known
      about the nutritional status and dietary practices of Bangladeshi adolescents in
      early pregnancy or associated factors. We used the baseline data of 1552 pregnant
      adolescents from a longitudinal, cluster-randomized effectiveness trial conducted
      in northwest Bangladesh. Forty-four percent of the adolescents were short for
      their age, 36% had low body mass index, 28% were anemic, 10% had iron deficiency,
      and 32% had vitamin A deficiency. The mean consumption of animal-source foods was
      10.3 times/week. In multivariate analysis, socioeconomic status, education, and
      food security were generally positively associated with anthropometric indicators
      and dietary practices but not with iron or vitamin A status. Our findings confirm
      that there is a high burden of undernutrition among these Bangladeshi adolescents
      in early pregnancy. Understanding factors related to undernutrition can help to
      identify adolescent pregnant women at higher risk and provide appropriate
      counseling and care.

PMID- 29457225
TI  - Aperture generation based on threshold segmentation for intensity modulated
      radiotherapy treatment planning.
AB  - PURPOSE: To reduce computation and decrease planning time with little or no loss
      in plan quality compared to the column-generation-based (cg) method, a simple
      method of aperture generation based on threshold segmentation (agts) is proposed.
      METHODS: The proposed agts strategy consists of two steps. First, a fuzzy
      controller is used for noise cancellation; then, new apertures are added using
      the threshold segmentation algorithm. We tested the proposed method on seven
      prostate tumor cases using the computational environment for radiotherapy
      research algorithms for the dose calculations and compared the results with those
      obtained by generating the plan aperture using the cg method. Specifically, the
      homogeneity index and conformity number of the planning target volume, organs at
      risk (OARs) sparing, and total planning time were compared among the two methods.
      RESULTS: The proposed agts technique produced treatment plans approximating the
      cg solution. Furthermore, the planning time required by the agts method was
      approximately 58.61% +/- 0.40 less than that required by the cg method.
      CONCLUSIONS: The agts algorithm can decrease planning time with little or no loss
      in plan quality compared to the cg method.

PMID- 29457226
TI  - Coordination and trade-offs among hydraulic safety, efficiency and drought
      avoidance traits in Amazonian rainforest canopy tree species.
AB  - Predicting responses of tropical forests to climate change-type drought is
      challenging because of high species diversity. Detailed characterization of
      tropical tree hydraulic physiology is necessary to evaluate community drought
      vulnerability and improve model parameterization. Here, we measured xylem
      hydraulic conductivity (hydraulic efficiency), xylem vulnerability curves
      (hydraulic safety), sapwood pressure-volume curves (drought avoidance) and wood
      density on emergent branches of 14 common species of Eastern Amazonian canopy
      trees in Paracou, French Guiana across species with the densest and lightest wood
      in the plot. Our objectives were to evaluate relationships among hydraulic traits
      to identify strategies and test the ability of easy-to-measure traits as proxies
      for hard-to-measure hydraulic traits. Xylem efficiency was related to
      capacitance, sapwood water content and turgor loss point, and other drought
      avoidance traits, but not to xylem safety (P50 ). Wood density was correlated (r
      = -0.57 to -0.97) with sapwood pressure-volume traits, forming an axis of
      hydraulic strategy variation. In contrast to drier sites where hydraulic safety
      plays a greater role, tropical trees in this humid tropical site varied along an
      axis with low wood density, high xylem efficiency and high capacitance at one end
      of the spectrum, and high wood density and low turgor loss point at the other.

PMID- 29457227
TI  - Fast or slow for the arborescent lycopsids?: Response to Thomas & Cleal (2018)
      'Arborescent lycophyte growth in the late Carboniferous coal swamps'.

PMID- 29457228
TI  - Usefulness of ultrasonography in diagnosis, percutaneous management and follow up
      of post-traumatic scalp pseudoaneurysms.
AB  - Pseudoaneurysms of the scalp are rare. Most common etiology is trauma. The
      patients usually present clinically with persistent painful swelling in the scalp
      few days after the trauma. The lesion may or may not be pulsatile clinically.
      Ultrasonography (US) is the best modality to assess these pseudoaneurysms. It not
      only helps in the diagnosis, but also to trace the offending arterial branch and
      helps in treatment. We present two cases of post-traumatic scalp pseudoaneurysms
      which were diagnosed with US and were managed by US-guided thrombin injection.
      Follow up US showed complete resolution. We highlight the importance of US scan
      in diagnosis, management, and follow up of scalp pseudoaneurysms.

PMID- 29457231
TI  - It's All Relative.
AB  - In this issue of the Hastings Center Report, Daniel Brudney suggests that
      clinicians have an overly deferential attitude toward their patients' surrogate
      decision-makers that is rooted in a wrongful investment of moral authority. He
      maintains that surrogate decision-makers have no moral right to decide for their
      loved ones and that their value in the decision-making process is limited to
      their knowledge of their loved one's preferences. If operationalized, Brudney's
      framework would ease the way for clinicians to remove a surrogate who cannot
      provide information relevant to the patient's preferences and to resort to a
      paternalistic model of decision-making. Brudney fails to consider that the value
      of the surrogate does not flow from the surrogate, but rather from the patient's
      moral claim to have decisions made for him or her by a loved one. This claim
      recognizes that surrogates have intrinsic value through their relationship to and
      knowledge of the patient. Bioethics consultation services can assist clinical
      teams in engaging with the human crowd that surrounds each patient and navigating
      conflicting values and goals. This relational approach embraces the "mire and
      blood" that is endemic to relationships and clinical encounters.

PMID- 29457230
TI  - Impact of hand eczema on quality of life: metropolitan versus non-metropolitan
      areas.
AB  - BACKGROUND: An inverse relationship between disease severity and health-related
      quality of life (HR-QoL) in patients with hand eczema is well established, but
      modifying effects of demographic variables have been less well studied.
      OBJECTIVE: To identify the influence of metropolitan versus non-metropolitan
      residence on the relationship between disease severity and HR-QoL in patients
      with occupational hand eczema. METHODS: The city of Copenhagen and the rest of
      Zealand were defined as metropolitan and non-metropolitan areas, respectively.
      Participants were 773 persons with occupational hand eczema. A questionnaire on
      the severity of hand eczema and HR-QoL was sent to all participants. RESULTS: The
      odds for reporting moderate to high severity of occupational hand eczema were
      significantly lower in the metropolitan population than in the non-metropolitan
      population [odds ratio (OR): 0.42; 95%CI: 0.23-0.75], whereas low dermatology
      related quality of life was more prevalent in metropolitan than in non
      metropolitan patients (OR: 1.31; 95%CI: 0.83-2.05), indicating that hand eczema
      had a more pronounced negative effect in metropolitan patients, in spite of less
      severe eczema. CONCLUSION: Our data indicate that area of residence has a
      modifying effect on the relationship between disease severity and HR-QoL, with a
      more negative impact on HR-QoL in metropolitan than in non-metropolitan areas.
      This information is important with respect to fully appreciating the burden of
      occupational hand eczema.

PMID- 29457229
TI  - Radiomics analysis of pulmonary nodules in low-dose CT for early detection of
      lung cancer.
AB  - PURPOSE: To develop a radiomics prediction model to improve pulmonary nodule (PN)
      classification in low-dose CT. To compare the model with the American College of
      Radiology (ACR) Lung CT Screening Reporting and Data System (Lung-RADS) for early
      detection of lung cancer. METHODS: We examined a set of 72 PNs (31 benign and 41
      malignant) from the Lung Image Database Consortium image collection (LIDC-IDRI).
      One hundred three CT radiomic features were extracted from each PN. Before the
      model building process, distinctive features were identified using a hierarchical
      clustering method. We then constructed a prediction model by using a support
      vector machine (SVM) classifier coupled with a least absolute shrinkage and
      selection operator (LASSO). A tenfold cross-validation (CV) was repeated ten
      times (10 * 10-fold CV) to evaluate the accuracy of the SVM-LASSO model. Finally,
      the best model from the 10 * 10-fold CV was further evaluated using 20 * 5- and
      50 * 2-fold CVs. RESULTS: The best SVM-LASSO model consisted of only two
      features: the bounding box anterior-posterior dimension (BB_AP) and the standard
      deviation of inverse difference moment (SD_IDM). The BB_AP measured the extension
      of a PN in the anterior-posterior direction and was highly correlated (r = 0.94)
      with the PN size. The SD_IDM was a texture feature that measured the directional
      variation of the local homogeneity feature IDM. Univariate analysis showed that
      both features were statistically significant and discriminative (P = 0.00013 and
      0.000038, respectively). PNs with larger BB_AP or smaller SD_IDM were more likely
      malignant. The 10 * 10-fold CV of the best SVM model using the two features
      achieved an accuracy of 84.6% and 0.89 AUC. By comparison, Lung-RADS achieved an
      accuracy of 72.2% and 0.77 AUC using four features (size, type, calcification,
      and spiculation). The prediction improvement of SVM-LASSO comparing to Lung-RADS
      was statistically significant (McNemar's test P = 0.026). Lung-RADS misclassified
      19 cases because it was mainly based on PN size, whereas the SVM-LASSO model
      correctly classified 10 of these cases by combining a size (BB_AP) feature and a
      texture (SD_IDM) feature. The performance of the SVM-LASSO model was stable when
      leaving more patients out with five- and twofold CVs (accuracy 84.1% and 81.6%,
      respectively). CONCLUSION: We developed an SVM-LASSO model to predict malignancy
      of PNs with two CT radiomic features. We demonstrated that the model achieved an
      accuracy of 84.6%, which was 12.4% higher than Lung-RADS.

PMID- 29457232
TI  - Tackling Obesity and Disease: The Culprit Is Sugar; the Response Is Legal
      Regulation.
AB  - It is staggering to observe the new normal in America: 37.9 percent of adults are
      obese, and 70.7 percent are either obese or overweight. One out of every five
      minors is obese. The real tragedy, of course, is the disability, suffering, and
      early death that devastates families and communities. But all of society pays,
      with the annual medical cost estimated at $147 billion. The causal pathways are
      complex, but if we drill down, sugar is a deeply consequential pathway to
      obesity, and the single greatest dietary source is sugar-sweetened beverages
      (SSBs). The copious amount of sugar in the American diet is no accident. Industry
      practices and regulatory failures have fueled this explosion. Yet there are
      sensible, effective interventions that would create the conditions for healthier
      behaviors. What are the key interventions, and how can we overcome the social,
      political, and constitutional roadblocks? Tobacco control offers a powerful
      model, suggesting that success requires a suite of interventions working in
      concert: labeling, warnings, taxation, portion sizes, product formulation,
      marketing restrictions, and bans in high-risk settings such as schools and
      hospitals. Each intervention deserves detailed analysis, but I'm kick-starting
      scholarly and policy conversation by systematically laying out the major legal
      tools.

PMID- 29457233
TI  - Market Language, Moral Language.
AB  - Those who advocate higher out-of-pocket spending, especially high deductibles, to
      keep health care costs better controlled without losing quality use market
      language to talk about how people should think about health care. Consumers-that
      is, patients-should hunt for bargains. Clip coupons. Shop around. Patients need
      to have more "skin in the game." Consumer-patients will then choose more
      carefully and prudently and use less unnecessary health care. Unfailingly, "skin"
      refers to having money at stake. Usually, those arguing for high deductibles
      express dismay or frustration that patients do not face the full ("true") cost of
      the health services they receive. Unfortunately, a lack of price transparency,
      the need to unbundle bundled groups of services to discover total price, and the
      challenge of validly and reliably measuring and disclosing quality make shopping
      for health care a challenge for even the savviest patient. Urgency, fear, and
      sickness that impairs peak cognitive function and other aspects of emotionally
      laden decision-making, even when "shared" with a physician, add obstacles to
      coupon clipping and tire kicking. Who has more at stake in health decisions than
      patients? Whose flesh is literally, not just figuratively, at risk?

PMID- 29457234
TI  - Community Engagement and Field Trials of Genetically Modified Insects and
      Animals.
AB  - New techniques for the genetic modification of organisms are creating new
      strategies for addressing persistent public health challenges. For example, the
      company Oxitec has conducted field trials internationally-and has attempted to
      conduct field trials in the United States-of a genetically modified mosquito that
      can be used to control dengue, Zika, and some other mosquito-borne diseases. In
      2016, a report commissioned by the National Academies of Sciences, Engineering,
      and Medicine discussed the potential benefits and risks of another strategy,
      using gene drives. Driving a desired genotype through a population of wild
      animals or insects could lead to irreversible genetic modification of an entire
      species. The NASEM report recommends community, stakeholder, and public
      engagement about potential uses of the technology, and it argues that the
      engagement should occur as research advances, well before gene drives are
      deployed. Yet what "engagement" means in practice is unclear. This article seeks
      clarity on this problem by offering a justification for community engagement and
      drawing out implications of this argument for the implementation and desired
      outcomes of community engagement. Community engagement is essential when it comes
      to research that would release genetically modified insects or animals into the
      environment. By contrast, obtaining informed consent from people who live near
      such a proposed field trial is neither necessary nor sufficient. Drawing on the
      epistemic and moral arguments for deliberative democracy, I propose two discrete
      mechanisms of community engagement: community advisory boards and deliberative
      forums, neither of which has been systematically incorporated into research
      governance. The proposed mechanisms would engender respect for persons who live
      near field trials, even when the results of deliberation override some
      individuals' preferences. Community engagement foregrounds the community in our
      thinking about humans' relationship to nature, and it implies that deciding to
      release genetically modified insects or animals into the wild ought to be a
      collective decision, not one made by product developers, policy-makers, private
      companies, research funders, or scientists alone.

PMID- 29457235
TI  - The Intimate Responsibility of Surrogate Decision-Making.
AB  - Daniel Brudney's clear-headed analysis, in this issue of the Hastings Center
      Report, of the difference between a patient's and a surrogate's right to make
      medical treatment decisions contributes to a longstanding conversation in
      bioethics. Brudney offers an epistemological and a moral argument for the
      patient's and the surrogate's right to decide. The epistemological argument is
      the same for both parties: the (competent) patient has a right to decide because
      she is presumed to know her own interests better than anyone else, and the
      surrogate is entitled to make decisions because she knows the patient better than
      anyone else. However, argues Brudney, the moral arguments are not parallel. The
      patient's moral right to decide for herself is an exercise of autonomy, but the
      only ground for the responsibility held by the surrogate, says Brudney, is that
      she knows the patient better than the health care professionals do. If in fact
      that's not the case, then she forfeits her right to be the patient's surrogate.
      For all the clarity and force of his argument, I think Brudney may be barking up
      the wrong tree. In cases of proxy decision-making, it's intimacy, not knowledge,
      that does the heavy moral lifting.

PMID- 29457236
TI  - Time Is Ethics.
AB  - Early in my career as a neonatologist, I was called into the hospital for a
      newborn who would not stop crying. Screaming, really. When I entered the unit, I
      was greeted by a loud, shrill, distinctive cry. After hearing the history and
      examining the baby, I just stood there for a while, watching and listening. It
      took some time, but eventually, I noticed a subtle regularity, a rhythmicity. I
      took off my watch, placed it on the bed next to the child, and found that the
      crying briefly grew louder about every six or seven seconds. This baby was having
      an atypical seizure. This preliminary diagnosis was followed by a conversation
      with the parents and a neurologist, transfer to the nearby academic center for an
      extensive evaluation, and the eventual demise of the child from a poorly
      understood disease. About a year later, I walked into the same unit and heard a
      cry I had heard only once before. I looked over to see the same mother at a
      newborn's bedside, with tears in her eyes, looking back at me. She knew what the
      coming days held for her and for her second child. That was over twenty years
      ago, but two images, or moments, remain with me. One is the watch on the bed next
      to the first baby; the other is the mother's expression of sadness the morning
      the second child was born. The image of the timepiece is perhaps instructive.

PMID- 29457238
TI  - Rationing Care through Collaboration and Shared Values.
AB  - Although "rationing" continues to be a dirty word for the public in health policy
      discourse, Nir Eyal and colleagues handle the concept exactly right in their
      article in this issue of the Hastings Center Report. They correctly characterize
      rationing as an ethical requirement, not a moral abomination. They identify the
      key health policy question as how rationing can best be done, not whether it
      should be done at all. They make a cogent defense of what they call "rationing
      through inconvenience" as a justifiable allocational technique. And they wisely
      call for research on the effectiveness and fairness of this approach and other
      methods of rationing. I fully agree with their approach to rationing and with
      their argument that the process they provocatively label "rationing through
      inconvenience" should not be rejected out of hand. But I believe they have
      underestimated two ways in which the practical impacts of rationing through
      inconvenience limit its potential usefulness: the asymmetry of its effect on
      patients and physicians and the way in which it reduces the capacity of health
      systems to learn from experience.

PMID- 29457239
TI  - Patient Care to Public Health to Synthetic Biology.
AB  - The January-February 2018 issue of the Hastings Center Report includes pieces
      addressing patient care concerns that lie at the original core of bioethics and
      pieces that reflect the field's growing breadth. Among the pieces getting at the
      original core is an article by philosopher Daniel Brudney on the moral values
      underpinning surrogate decision-making. The article and the two commentaries that
      follow it contribute to the debate on the moral authority of surrogate decision
      makers. Several items in the issue take up matters of public health and health
      policy. For example, the lead article, by Nir Eyal, examines the ethics of using
      inconvenience-waiting lists and the like-to constrain the consumption of health
      care services, and a commentary by Lawrence Gostin examines the regulation of
      sugary beverages. A supplement to the issue contains a special report about the
      tools and processes used to assess the impact of emerging technologies, with a
      focus on synthetic biology.

PMID- 29457240
TI  - Manuscript Reviewers 2017.

PMID- 29457241
TI  - Can Rationing through Inconvenience Be Ethical?
AB  - In this article, we provide a comprehensive analysis and a normative assessment
      of rationing through inconvenience as a form of rationing. By "rationing through
      inconvenience" in the health sphere, we refer to a nonfinancial burden (the
      inconvenience) that is either intended to cause or has the effect of causing
      patients or clinicians to choose an option for health-related consumption that is
      preferred by the health system for its fairness, efficiency, or other
      distributive desiderata beyond assisting the immediate patient. We argue that
      under certain conditions, rationing through inconvenience may turn out to serve
      as a legitimate and, compared to direct rationing, even a preferable tool for
      rationing; we propose a research agenda to identify more precisely when that
      might be the case and when, alternatively, rationing through inconvenience
      remains ethically undesirable. After defining and illustrating rationing through
      inconvenience, we turn to its moral advantages and disadvantages over other
      rationing methods. We take it as a starting assumption that rationing, understood
      as scarce-resource prioritization, is inevitable and, in a society that has goals
      beyond optimizing health care for individual patients-such as improving societal
      health care, education, or overall welfare-prudent and fair.

PMID- 29457242
TI  - Bioethics as care work.
AB  - German philosopher Martin Heidegger argued that humans are defined by care. The
      term he used, "Sorge," picks out a wide range of caring relations, including
      sorrow, worry, the making of arrangements, and even fending for another. Since
      coming to The Hastings Center, I've been struck by the genuine care definitive of
      its scholars' relationship to their work. Care about newborns, the elderly, and
      nonhuman animals. Care about doctors, nurses, and health care institutions. Care
      expressed in the panoply of ways biomedical knowledge and practices inform our
      havings, doings, and beings in the world. Perhaps in its better moments,
      bioethics just is care work. But care work is hard and messy.

PMID- 29457243
TI  - Raising the Stakes for Nondiscrimination Protections in the ACA.
AB  - In the struggle over the durability of the Affordable Care Act, defenders of the
      ACA stand guard at many fronts. A major contribution of the ACA to
      nondiscrimination law, however, appears increasingly vulnerable. The ACA
      established significant new nondiscrimination protections for patients under
      section 1557 and its implementing regulations. Several of these regulations
      including protections on the basis of gender identity and pregnancy termination
      are now under reconsideration at the Department of Health and Human Services,
      after a nationwide injunction lasting almost a year. Nondiscrimination laws
      matter, of course, because they promote equal access to health care. But focusing
      on discriminatory behavior alone is a narrow view of the purpose and potential of
      nondiscrimination rules-and underestimates the stakes of softening section 1557.
      To evaluate these protections, we must consider not only their impacts on
      discriminatory behavior but also their behavioral and attitudinal impacts on
      patients and communities. This is because supportive or stigmatizing rules can
      exert an expressive effect: laws communicate information about prevailing social
      norms, they give some norms greater authority by virtue of the state's support,
      and they can shape community values. Through these expressive impacts,
      nondiscrimination laws may affect not only discriminatory behavior in health
      activities but also the attitudes, beliefs, and decisions of people who are
      legally protected.

PMID- 29457244
TI  - The Different Moral Bases of Patient and Surrogate Decision-Making.
AB  - : My topic is a problem with our practice of surrogate decision-making in health
      care, namely, the problem of the surrogate who is not doing her job-the surrogate
      who cannot be reached or the surrogate who seems to refuse to understand or to be
      unable to understand the clinical situation. The analysis raises a question about
      the surrogate who simply disagrees with the medical team. One might think that
      such a surrogate is doing her job-the team just doesn't like how she is doing it.
      My analysis raises the question of whether (or perhaps when) she should be
      overridden. In approaching this problem, I focus not on the range of difficulties
      in practice but on the underlying moral conceptual issue. My concern will be to
      show that the moral values that underpin patient decision-making are
      fundamentally different from those that underpin surrogate decision-making.
      Identifying the distinctions will set parameters for any successful solution to
      the "Who should decide?" QUESTION: A patient has a specific kind of moral right
      to make her own medical decisions. A surrogate has no analogous moral right to
      decide for someone else. We want the surrogate to make the decision because we
      believe that she has a relevant epistemological advantage over anyone else on the
      scene. If and when she has no such advantage or if she refuses or is unable to
      use it, then there might not be sufficient reason to let her be the decision
      maker.

PMID- 29457245
TI  - Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy
      in the neocortex and the hippocampus.
AB  - OBJECTIVE: Depression is associated with accelerated aging and age-related
      diseases. However, mechanisms underlying this relationship remain unclear. The
      aim of this study was to longitudinally assess the link between depressive
      symptoms, brain atrophy, and cortisol levels. METHOD: Participants from the
      Betula prospective cohort study (mean age = 59 years, SD = 13.4 years) underwent
      clinical, neuropsychological and brain 3T MRI assessments at baseline and a 4
      year follow-up. Cortisol levels were measured at baseline in four saliva samples.
      Cortical and hippocampal atrophy rates were estimated and compared between
      participants with and without depressive symptoms (n = 81) and correlated with
      cortisol levels (n = 49). RESULTS: Atrophy in the left superior frontal gyrus and
      right lingual gyrus developed in parallel with depressive symptoms, and in the
      left temporal pole, superior temporal cortex, and supramarginal cortex after the
      onset of depressive symptom. Depression-related atrophy was significantly
      associated with elevated cortisol levels. Elevated cortisol levels were also
      associated with widespread prefrontal, parietal, lateral, and medial temporal
      atrophy. CONCLUSION: Depressive symptoms and elevated cortisol levels are
      associated with atrophy of the prefrontal and limbic areas of the brain.

PMID- 29457246
TI  - Randomized, controlled, prospective clinical trial of autologous greater omentum
      free graft versus autogenous cancellous bone graft in radial and ulnar fractures
      in miniature breed dogs.
AB  - OBJECTIVE: To determine the rate of radiographic healing, complications,
      vascularization, and bone density after repair of radial and ulnar fractures in
      dogs <6 kg that were treated with an autogenous cancellous bone graft (BG) or
      free autologous omentum graft (OG). STUDY DESIGN: Prospective, randomized,
      controlled clinical trial with owners/radiologists blinded to treatment. ANIMALS:
      25 dogs with naturally occurring traumatic radial/ulnar fractures. METHODS:
      Fractures underwent plate fixation with OG or BG. Power Doppler ultrasonographic,
      computed tomographic (CT), and radiographic examinations of the affected
      antebrachium were performed preoperatively and every 3 weeks postoperatively
      until healed. Pressure-sensitive walkway gait analysis and owner and veterinarian
      assessments were obtained preoperatively (0 weeks) and 3, 6, 9, 12, and 24 weeks
      postoperatively. RESULTS: Owner/veterinarian assessments improved postoperatively
      but did not differ significantly between groups. The improvement in peak vertical
      force/vertical impulse was greater in dogs with OG than in those with BG,
      beginning 3 weeks postoperatively. Radiographic healing occurred earlier in bones
      treated with OG (median, 9 weeks) than in those treated with BG (12 weeks).
      Cortical bone density derived from CT of the distal ulna was higher in bones with
      BG compared with bones with OG. Signal intensity and the number of vessels in the
      fracture callus declined over time in both groups, according to results of
      ultrasonography. However, bones retained more vessels and greater signal
      intensity when treated with OG compared with treatment with BG, according to
      multiple views at 6 and 9 weeks postoperatively. CONCLUSION: Omental grafting was
      not associated with major complications, and it accelerated bone healing and
      return to weight bearing in dogs. CLINICAL SIGNIFICANCE: Omental grafting should
      be considered as an adjunct to stabilization of antebrachial fractures in toy and
      small breed dogs.

PMID- 29457247
TI  - Development of a multiroute physiologically based pharmacokinetic model for
      orbifloxacin in rabbits.
AB  - To predict the orbifloxacin concentrations in rabbits after multiple routes of
      administration, a flow-limited multiroute physiologically based pharmacokinetic
      (PBPK) model was developed. Three routes of administration (IV, IM, and PO) were
      incorporated into this model. Physiological parameters including tissue weights
      and blood flows through different tissues were obtained from the literature. The
      tissue/plasma partition coefficients (PX s) for noneliminating tissues were
      calculated according to the area method, while the PX s for kidney and the rest
      of the body compartment, together with other parameters for absorption and
      elimination, were optimized based on the published concentrations. The
      comparisons between predicted and observed orbifloxacin concentrations proved its
      validity, and the present model predicted available concentration data well,
      including those in liver, kidney, muscle, lung, heart, and plasma after oral,
      intravenous, or intramuscular administration. A local sensitivity analysis was
      also performed, which showed that the parameters for oral absorption were most
      influential on the orbifloxacin concentrations. This model was used to predict
      plasma and tissue concentrations after multiple oral or intramuscular
      administration. This study demonstrated the feasibility of predicting drug
      residues in minor species after multiple routes of administration in the extra
      label manner using the PBPK modeling.

PMID- 29457248
TI  - Duty hours restriction for our surgical trainees: An ethical obligation or a bad
      idea?
AB  - To ensure patient safety and protect the well-being of interns and residents, the
      Accreditation Council for Graduate Medical Education (ACGME) issued guidelines in
      2003 limiting the working hours of physician trainees. Although many supported
      the goals of the ACGME, institutions struggled to restructure their programs and
      hire staff required by this unfunded mandate. Numerous studies have analyzed the
      effects of duty hours restrictions on patient outcomes and physician training
      over the past 15 years. Most agree that duty hours restrictions improved well
      being of house officers, but these improvements came at the expense of
      continuity, and patient hand-offs led to medical errors. Effects on resident
      training are program specific, with duty hours restrictions having the most
      deleterious effects on surgical disciplines. Because veterinary specialists
      assume a similar role in providing 24-hour patient care, interns and residents
      face work-related stress as a result of extended working hours, on-call duty, and
      an increasingly complex caseload. The North Carolina State Veterinary Hospital is
      staffed by approximately 100 house officers representing almost every veterinary
      specialty group. We surveyed departing house officers regarding their quality of
      life and training experience. Sixty-six percent of interns and residents reported
      that they do not have time to take care of personal needs, and 57%-62% felt
      neutral or dissatisfied with their mental and physical well-being. Most trainees
      believed that decreased duty hours would improve learning, but 42% believed that
      decreased caseload would be detrimental to training. Veterinary educators must
      consider post-DVM veterinary training guidelines that maintain patient care with
      a good learning environment for interns and residents.

PMID- 29457249
TI  - Gut bacteria of cockroaches are a potential source of antibacterial compound(s).
AB  - : Here, we hypothesized that the microbial gut flora of animals/pests living in
      polluted environments, produce substances to thwart bacterial infections. The
      overall aim of this study was to source microbes inhabiting unusual environmental
      niches for potential antimicrobial activity. Two cockroach species,
      Gromphadorhina portentosa (Madagascar) and Blaptica dubia (Dubia) were selected.
      The gut bacteria from these species were isolated and grown in RPMI 1640 and
      conditioned media were prepared. Conditioned media were tested against a panel of
      Gram-positive (Methicillin-resistant Staphylococcus aureus, Streptococcus
      pyogenes, Bacillus cereus) and Gram-negative (Escherichia coli K1, Salmonella
      enterica, Serratia marcescens, Pseudomonas aeruginosa, Klebsiella pneumoniae)
      bacteria, as well as the protist pathogen, Acanthamoeba castellanii. The results
      revealed that the gut bacteria of cockroaches produce active molecule(s) with
      potent antibacterial properties, as well as exhibit antiamoebic effects. However,
      heat-inactivation at 95 degrees C for 10 min had no effect on conditioned media
      mediated antibacterial and antiamoebic properties. These results suggest that
      bacteria from novel sources i.e. from the cockroach's gut produce molecules with
      bactericidal as well as amoebicidal properties that can ultimately lead to the
      development of therapeutic drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      bacteria isolated from unusual dwellings such as the cockroaches' gut are a
      useful source of antibacterial and antiamoebal molecules. These are remarkable
      findings that will open several avenues in our search for novel antimicrobials
      from unique sources. Furthermore studies will lead to the identification of
      molecules to develop future antibacterials from insects.

PMID- 29457250
TI  - My tribute to Ralph Lazzara, MD.

PMID- 29457251
TI  - Involvement of flexures in an adolescent patient with dermatomyositis: extension
      of inverse Gottron papules?

PMID- 29457252
TI  - Body image flexibility: A predictor and moderator of outcome in transdiagnostic
      outpatient eating disorder treatment.
AB  - OBJECTIVE: Predictors of attrition and predictors and moderators of outcome were
      explored in a transdiagnostic sample of patients who received ten-session
      cognitive behavioral therapy (CBT-T) for nonunderweight eating disorders. Body
      image flexibility, a protective positive body image construct, was hypothesized
      to be a significant moderator. METHOD: Data from two case series were combined to
      form a sample of 78 participants who received CBT-T. Baseline measures of body
      image, negative affect, personality, and motivation (readiness to change and self
      efficacy) were included as potential predictors. Global eating disorder
      psychopathology at each assessment point (baseline, mid- and post-treatment, 1-
      and 3-month follow-up) was the outcome variable. Predictors of attrition were
      assessed using logistic regression, and multilevel modeling was applied for
      predictors and moderators of outcome. RESULTS: Body image flexibility emerged as
      the strongest predictor and moderator of global eating disorder psychopathology,
      followed by body image avoidance. Body checking, negative affect, personality
      beliefs, and self-efficacy were significant predictors of global eating disorder
      psychopathology. DISCUSSION: Higher body image flexibility predicted lower global
      eating disorder psychopathology at every assessment point. Further research is
      required to replicate findings and explore the benefit of focusing on positive
      body image in treatment.

PMID- 29457253
TI  - Power transformations improve interpolation of grids for molecular mechanics
      interaction energies.
AB  - A common strategy for speeding up molecular docking calculations is to precompute
      nonbonded interaction energies between a receptor molecule and a set of three
      dimensional grids. The grids are then interpolated to compute energies for ligand
      atoms in many different binding poses. Here, I evaluate a smoothing strategy of
      taking a power transformation of grid point energies and inverse transformation
      of the result from trilinear interpolation. For molecular docking poses from 85
      protein-ligand complexes, this smoothing procedure leads to significant accuracy
      improvements, including an approximately twofold reduction in the root mean
      square error at a grid spacing of 0.4 A and retaining the ability to rank docking
      poses even at a grid spacing of 0.7 A. (c) 2018 Wiley Periodicals, Inc.

PMID- 29457254
TI  - Primordial odontogenic tumour: report of two cases.
AB  - AIMS: Primordial odontogenic tumour (POT) is a rare mixed odontogenic neoplasm
      that is composed of primitive ectomesenchyme resembling dental papilla, surfaced
      by odontogenic epithelium resembling inner enamel epithelium, without hard tissue
      formation. Most reported cases have presented in the posterior mandible as a well
      demarcated radiolucency associated with an unerupted tooth in the first two
      decades of life. The aim of this report is to describe the clinicopathological
      features of two more cases of POT. METHODS AND RESULTS: Each presented as an
      asymptomatic well-delineated radiolucency in the mandible in a 15-year-old female
      and an 18-year-old male, respectively. Both tumours were composed of a
      proliferation of plump spindle and stellate cells in delicately collagenous and
      myxoid stroma, surfaced by columnar-squamous epithelial cells with reverse
      nuclear polarisation at the tumour periphery. In one case, the formation of
      abortive tooth germ-like structures was noted. This has not been reported
      previously and supports the hypothesis of the primordial nature of this tumour.
      Both patients showed no recurrence at 3- and 20-month follow-up, respectively.
      CONCLUSION: This report describes two additional cases of POT for a total of 11
      cases reported in the English language literature.

PMID- 29457255
TI  - Pregnancy on vandetanib in metastatic medullary thyroid carcinoma associated with
      multiple endocrine neoplasia type 2B.

PMID- 29457256
TI  - Innovation in values based public health nursing student selection: A qualitative
      evaluation of candidate and selection panel member perspectives.
AB  - OBJECTIVES: Values based recruitment emerges from the premise that a high degree
      of value congruence, or the extent to which an individual's values are similar to
      those of the health organization in which they work, leads to organizational
      effectiveness. The aim of this evaluation was to explore how candidates and
      selection panel members experienced and perceived innovative methods of values
      based public health nursing student selection. DESIGN AND SAMPLE: The evaluation
      was framed by a qualitative exploratory design involving semi-structured
      interviews and a group exercise. Data were thematically analyzed. Eight semi
      structured interviews were conducted with selection panel members. Twenty-two
      successful candidates took part in a group exercise. INTERVENTION: The use of
      photo elicitation interviews and situational judgment questions in the context of
      selection to a university-run public health nursing educational program was
      explored. RESULTS: While candidates were ambivalent about the use of photo
      elicitation interviews, with some misunderstanding the task, selection panel
      members saw the benefits for improving candidate expression and reducing gaming
      and deception. Situational interview questions were endorsed by candidates and
      selection panel members due to their fidelity to real-life problems and the
      ability of panel members to discern value congruence from candidates' responses.
      CONCLUSIONS: Both techniques offered innovative solutions to candidate selection
      for entry to the public health nursing education program.

PMID- 29457257
TI  - Pharmacokinetics, pharmacodynamics, and metabolism of acepromazine following
      intravenous, oral, and sublingual administration to exercised Thoroughbred
      horses.
AB  - Acepromazine is a tranquilizer used commonly in equine medicine. This study
      describes serum and urine concentrations and the pharmacokinetics and
      pharmacodynamics of acepromazine following intravenous, oral, and sublingual (SL)
      administration. Fifteen exercised adult Thoroughbred horses received a single
      intravenous, oral, and SL dose of 0.09 mg/kg of acepromazine. Blood and urine
      samples were collected at time 0 and at various times for up to 72 hr and
      analyzed for acepromazine and its two major metabolites (2-(1-hydroxyethyl)
      promazine and 2-(1-hydroxyethyl) promazine sulfoxide) using liquid chromatography
      tandem mass spectrometry. Acepromazine was also incubated in vitro with whole
      equine blood and serum concentrations of the parent drug and metabolites
      determined. Acepromazine was quantitated for 24 hr following intravenous
      administration and 72 hr following oral and SL administration. Results of in
      vitro incubations with whole blood suggest additional metabolism by RBCs. The
      mean +/- SEM elimination half-life was 5.16 +/- 0.450, 8.58 +/- 2.23, and 6.70 +/
      2.62 hr following intravenous, oral, and SL administration, respectively. No
      adverse effects were noted and horses appeared sedate as noted by a decrease in
      chin-to-ground distance within 5 (i.v.) or 15 (p.o. and SL) minutes
      postadministration. The duration of sedation lasted 2 hr. Changes in heart rate
      were minimal.

PMID- 29457258
TI  - Quality of Prescribing by Physicians, Nurse Practitioners, and Physician
      Assistants in the United States.
AB  - OBJECTIVE: Nurse practitioners (NPs) and physician assistants (PAs) have
      increasingly broad prescribing authority in the United States, yet little is
      known regarding how the quality of their prescribing practices compares with that
      of physicians. The objective of this study was to compare the quality of
      prescribing practices of physicians and nonphysician providers. METHODS: A serial
      cross-sectional analysis of the 2006-2012 National Ambulatory Medical Care Survey
      and National Hospital Ambulatory Medical Care Survey was performed. Ambulatory
      care services in physician offices, hospital emergency departments, and
      outpatient departments were evaluated using a nationally representative sample of
      patient visits to physicians, NPs, and PAs. Main outcome measures were 13
      validated outpatient quality indicators focused on pharmacologic management of
      chronic diseases and appropriate medication use. RESULTS: A total of 701,499
      sampled patient visits were included during the study period, representing ~8.33
      billion visits nationwide. Physicians were the primary provider for 96.8% of all
      outpatient visits examined; NPs and PAs each accounted for 1.6% of these visits.
      The proportion of eligible visits where quality standards were met ranged from
      34.1% (angiotensin-converting enzyme inhibitor use for congestive heart failure)
      to 89.5% (avoidance of inappropriate medications among elderly). The median
      overall performance across all indicators was 58.7%. On unadjusted analyses,
      differences in quality of care between nonphysicians and physicians for each
      indicator did not consistently favor one practitioner type over others. After
      adjustment for potentially confounding patient and provider characteristics, the
      quality of prescribing by NPs and PAs was similar to the care delivered by
      physicians for 10 of the 13 indicators evaluated, and no consistent directional
      association was found between provider type and indicator fulfillment for the
      remaining measures. CONCLUSIONS: Although significant shortfalls exist in the
      quality of ambulatory prescribing across all practitioner types, the quality of
      care delivered by nonphysicians and physicians was generally comparable.

PMID- 29457259
TI  - Prosthetic mitral valve thrombosis, malfunction, and paroxysmal mitral
      regurgitation.
AB  - Intermittent dysfunction of mechanical mitral valve prosthesis is an uncommon
      condition. It carries serious clinical implications if unrecognized. Here, we
      present a case of a 28-year-old female with a history of rheumatic multivalvular
      disease, for which she had undergone double valve replacement and tricuspid
      annuloplasty. Six months later, she presented with heart failure. Clinical
      examination revealed intermittent loss of closing clicks followed by a
      pansystolic murmur at the apex, suggestive of mitral prosthetic valve
      dysfunction. We highlight the echocardiographic findings of paroxysmal mitral
      valvular regurgitation secondary to prosthetic valve malfunction secondary to
      prosthetic valve thrombosis.

PMID- 29457260
TI  - Prediction of postoperative atrial fibrillation with left atrial mechanical
      functions and NT-pro ANP levels after coronary artery bypass surgery: A three
      dimensional echocardiography study.
AB  - OBJECTIVE: Postoperative AF (POAF) is the most common cause of morbidity after
      coronary artery bypass surgery. In this study, we aimed to show the relationship
      between POAF and N-terminal pro-atrial natriuretic peptide (NT-pro ANP) levels
      and the relationship between mechanical functions and left atrial volume measured
      using preoperative three-dimensional echocardiography (3D ECHO) among patients
      that will undergo isolated coronary artery bypass grafting (CABG) in elective
      conditions. METHOD: Sixty-six consecutive patients (51 male, 15 female) who were
      decided to undergo CABG and had normal sinus rhythm were involved in the study.
      Patients were followed by continuous electrocardiography monitoring and daily
      electrocardiogram. LA volume and mechanical functions were calculated with 3D
      ECHO. In addition, for the analysis of plasma levels of NT-pro ANP, blood samples
      were collected before the surgery. RESULTS: During follow-up after the operation,
      15 patients (22.7%) had postoperative atrial fibrillation. LA Vmax, Vmin, VpreA
      values were higher (P < .001, P = .004, P < .001 respectively) Also in POAF
      developed group and SR group, LAVI values were 27.56 +/- 4.2 and 20.7 +/- 4.64
      mL/m2 , respectively (P < .001). In POAF-developing group, NT-pro ANP levels were
      significantly higher (P < .001). In multiple logistic regression analysis, age
      (beta = 0.355, P = .007) and LAVI (beta = 0.668, P = .012) are independent
      predictors of POAF. CONCLUSION: It was found that 3D echocardiography can be used
      as a helping noninvasive method to show subclinical atrial volume and mechanical
      dysfunction in patients undergoing CABG. Also, blood levels of NT-pro ANP in POAF
      group were increased.

PMID- 29457261
TI  - Angiography vs transesophageal echocardiography-guided patent foramen ovale
      closure: A propensity score matched analysis of a two-center registry.
AB  - OBJECTIVES: The purpose of this study is to compare the long-term outcomes of
      patent foramen ovale (PFO) closure using angiography or transesophageal
      echocardiography as procedural guidance. BACKGROUND: The interventional treatment
      is emerging as a safe and efficient option for patients with high likelihood of
      PFO-related cryptogenic stroke and high risk of recurrence. The "gold-standard"
      guidance technique remains an issue. METHODS: Two cohorts of patients undergoing
      PFO closure for cryptogenic stroke in two catheterization laboratories of the
      same institution, using similar inclusion criteria but different guidance, were
      compared with propensity score matching. RESULTS: A total of 374 patients were
      enrolled, 161 in Angio-group and 213 in Echo-group. No difference was detected in
      the procedural complication rate. In Angio-group, radiological exposure (P =
      .001) and 6-month residual shunt (16.8% vs 8.0%, P = .015) were higher. After a
      mean follow-up of 41 +/- 30 months, 28 patients (7.5%) presented any adverse
      event (death, recurrent cerebral ischemia, device-related complications,
      reintervention), with a higher rate in Angio-group (13.0% vs 3.3%, P = .001),
      mainly due to repeated percutaneous intervention (10.6% vs 1.4%, P = .001). The
      results were confirmed after propensity score matching (118 patients/group). The
      rate of recurrent cerebral ischemia was 1.9% and was not significantly different
      in the two groups. Intra-procedural guidance and atrial septum aneurysm were
      independent predictors of the composite primary endpoint (OR 1.2, P = .016).
      CONCLUSIONS: The use of intra-procedural transesophageal echocardiography (TEE)
      guidance for PFO closure allows lower residual shunt rate, radiological exposure,
      and adverse events, mainly driven by a significant reduction in percutaneous
      reintervention.

PMID- 29457262
TI  - Handheld reflectance confocal microscopy, dermatoscopy and histopathological
      correlation of common inflammatory balanitis.
AB  - BACKGROUND: The term balanitis includes a variety of inflammatory skin diseases
      involving the glans penis whose clinical diagnosis may be challenging. A biopsy
      is often required to obtain a definitive diagnosis, although it is barely
      accepted by patients. Reflectance confocal microscopy (RCM), that provides a real
      time, en face imaging of the epidermis and upper dermis, is currently utilized
      for the diagnosis of some neoplastic and inflammatory skin diseases. The aim of
      this study was to analyze the RCM handheld findings of some common balanitis and
      to correlate them with dermatoscopy and histopathological features. MATERIALS AND
      METHODS: Thirty-two patients with biopsy-proven diagnosis of psoriatic balanitis
      (10 patients), Zoon's balanitis (11 patients) and lichen sclerosus et atrophicus
      (11 patients) were evaluated using a handheld RCM device and *10 dermatoscopy.
      RESULTS: At the end of the study, each disorder presented specific RCM patterns
      that correlated with dermatoscopy and histopathological findings. CONCLUSION: The
      use of handheld RCM as complementary tool in everyday clinical practice for the
      evaluation of inflammatory diseases involving sensitive areas such as male
      genitalia, may contribute to reduce the need of invasive procedures.

PMID- 29457263
TI  - Acute myocarditis with thrombus near left ventricular outflow tract.
AB  - A young woman presented with fulminant heart failure. Transthoracic
      echocardiography revealed severe left ventricular dysfunction with a mass
      adjacent to the basal anterior wall, near the left ventricular outflow tract
      (LVOT). The cause of the acute heart failure and mass was unclear.
      Transesophageal echocardiography, with contrast, and cardiac magnetic resonance
      imaging findings were consistent with thrombus near the LVOT. Cardiac biopsy
      suggested giant cell myocarditis. The patient was treated with anticoagulation,
      steroids, and heart failure medications with resolution of the thrombus. This
      case was remarkable for the location of thrombus at the base of the ventricle.

PMID- 29457264
TI  - Comparison of left atrial size and function in hypertrophic cardiomyopathy and in
      Fabry disease with left ventricular hypertrophy.
AB  - BACKGROUND: Fabry disease (FD) and hypertrophic cardiomyopathy (HCM) are two
      diseases with a different pathophysiology, both cause left ventricular
      hypertrophy (LVH) and myocardial fibrosis. Although remodeling and systolic
      dysfunction of the left atrium (LA) are associated with atrial fibrillation and
      stroke in HCM, changes in the size and function of the LA have not been well
      studied in FD with LVH. METHODS: The following groups were studied prospectively,
      and their respective findings compared: 19 patients with non-obstructive HCM
      (Group I), 20 patients with a diagnosis of Fabry cardiomyopathy (Group II), and
      20 normal subjects matched for sex and age (Group III). Left ventricular mass
      index was measured using Devereux' formula, left atrial volume with Simpson's
      biplane method and left atrial mechanical function, including strain and strain
      rate, was measured using the speckle tracking technique. Strain and strain rate
      of the reservoir were measured during the three phases: reservoir (SR S), passive
      conduit (SR E) and atrial contraction (SR A). RESULTS: Patients with HCM had a
      larger left atrial volume than patients with FD (48.16 +/- 14.3 mL/m2 vs 38.9 +/-
      14.9 mL/m2 respectively, P < .001), but in both disorders there was a severe
      decrease in left atrial function: reservoir strain in the apical four-chamber
      view: 17.47% in HCM vs 22.5% in FD, P = .24), strain rate in the apical chamber
      view: SR A: -0.80/seconds in HCM vs -1.04/seconds in FD (P = .88), SR S:
      0.69/seconds in HCM vs 0.93 in FD (P = .12), SR E: -0.80 seconds in HCM vs 
      0.97/seconds in FD (P = .18). CONCLUSIONS: In this echocardiographic study we
      used speckle tracking to assess left atrial mechanical function and showed that
      FD is associated to an atrial cardiomyopathy, affecting the three phasic
      functions of the LA. Although in patients with HCM left atrial volume is larger
      than in patients with FD, both disorders exhibit severe decrease in left atrial
      function. These findings should be considered, given the potentially serious
      complications that can occur with the two diseases.

PMID- 29457265
TI  - The role of type 2 diabetes mellitus on hypertensive-related aortic stiffness.
AB  - BACKGROUND: Hypertension is strongly related to arterial stiffness in a cause
      effect fashion. Diabetes mellitus is also thought to determine vascular damage,
      mostly by means of advanced glycosylation end-products (AGEs). Aim of our study
      was to study the role of type 2 diabetes mellitus (T2DM) as regard ascending
      aortic elastic properties in hypertensive patients. METHODS: We prospectively
      enrolled outpatients with hypertension (n = 99) and type 2 diabetes mellitus plus
      hypertension (n = 42) without cardiovascular events. They underwent a
      transthoracic echocardiography to measure aortic diameters, aortic elastic
      properties (ie, compliance, distensibility, stiffness index, Peterson's elastic
      modulus, pulse wave velocity, M-mode strain), tissue Doppler imaging (TDI) to
      calculate diastolic (E' and A') and systolic (S') velocities, and tissue strain.
      Multivariable analysis was run to assess the association between T2DM and these
      variables after correcting for possible confounders (age, sex, body mass index
      [BMI], dyslipidemia). RESULTS: The two groups did not differ as regards age, sex,
      BMI, and blood pressure. However, T2DM patients were more likely to be
      dyslipidemic (43% vs 71%, P = .003). Aortic diameters were similar in the two
      groups, but the aortic elastic properties significantly more impaired in T2DM
      group. At multivariable analysis, stiffness index, Peterson's elastic modulus,
      the TDI waves, and the tissue strain remained associated with the co-presence of
      T2DM and hypertension. CONCLUSION: Our data suggest that people suffering from
      both T2DM and hypertension have more impaired aortic elastic properties than
      those hypertensive alone. Considering the prognostic role of aortic stiffness,
      these patients may benefit from a closer follow-up.

PMID- 29457266
TI  - Polyvalvular heart disease syndrome.
AB  - An adult case of polyvalvular heart disease syndrome diagnosed in an adult is
      presented. The characteristic facies and echocardiographic features of this rare
      autosomal dominant connective tissue disorder are presented.

PMID- 29457267
TI  - Involving children and young people in clinical research through the forum of a
      European Young Persons' Advisory Group: needs and challenges.
AB  - Children and young people are seen as fundamental to the design and delivery of
      clinical research as active and reflective participants. In Europe, involvement
      of children and young people in clinical research is promoted extensively in
      order to engage young people in research as partners and to give them a voice to
      raise their own issues or opinions and for their involvement in planning and
      decision making in addition to learning research skills. Children and young
      people can be trained in clinical research through participation in young person
      advisory groups (YPAGs). Members of YPAGs assist other children and young people
      to learn about clinical research and share their experience and point of view
      with researchers, thereby possibly influencing all phases of research including
      the development and prioritization of research questions, design and methods,
      recruitment plans, and strategies for results dissemination. In the long term,
      the expansion of YPAGs in Europe will serve as a driving force for refining
      pediatric clinical research. It will help in a better definition of research
      projects according to the patients' needs. Furthermore, direct engagement of
      children and young people in research will be favorable to both researchers and
      young people.

PMID- 29457268
TI  - The lymphoid cell network in the skin.
AB  - Cutaneous immunity represents a crucial component of the mammalian immune
      response. The presence of a large array of commensal microorganisms along with a
      myriad of environmental stresses necessitates constant immuno-surveillance of the
      tissue. To achieve a perfect balance between immune-tolerance and immune
      activation, the skin harbors strategically localized immune cell populations that
      modulate these responses. To maintain homeostasis, innate and adaptive immune
      cells assimilate microenvironmental cues and coordinate cellular and molecular
      functions in a spatiotemporal manner. The role of lymphoid cells in cutaneous
      immunity is gaining much appreciation due to their important roles in regulating
      skin health and pathology. In this review, we aim to highlight the recent
      advances in the field of cutaneous lymphoid biology.

PMID- 29457269
TI  - Ambulatory blood pressure monitoring in living kidney donors: What changes in 10
      years?
AB  - In renal transplantation, living donations have more significant benefits
      compared to cadaveric donations. However, a probable increase in blood pressure
      following donation should also be kept in mind. In this study, we investigated
      the long-term changes in blood pressure in living kidney donors using ambulatory
      blood pressure monitoring and we explored the e-GFR and albuminuria/proteinuria
      measurements at 3 time points. Twenty-eight living kidney donors and 39 healthy
      individuals were evaluated and compared at the baseline and later at the 10th
      year. At the 10th year, creatinine levels were higher and eGFR levels were lower
      in the donors, whereas the systolic and diastolic measurements of the donors and
      controls and the prevalence of nondipping in the donors and controls were
      similar. Our study may be underpowered due to its small population size. However,
      our results at the 10th year follow-up indicated that the risk of hypertension
      might not seem to have increased in the well-selected donors. In addition, the
      majority of our donors had preserved their GFR values. Therefore, we can suggest
      that living kidney donation appears to be safe in well-selected patients over a
      10-year time frame.

PMID- 29457271
TI  - Does the temperature of an artificial tear affect its comfort?
AB  - BACKGROUND: Refrigerated eye-drops have been advocated in cases of ocular
      allergies to provide a soothing effect upon instillation. This notion continues
      to be promoted by practitioners for artificial tears (AT) in the management of
      dry eye (DE) with little support in the literature. To further substantiate
      claims of a soothing effect of cold eye-drops, the aim of this study was to
      determine if refrigeration of an AT enhanced the subjective comfort upon
      instillation. METHODS: Participants with mild to moderate DE participated in an
      open label contralateral study of two weeks duration. Each participant instilled
      Systane Ultra (Alcon Laboratories) in the morning (between 6.00-10.00 hours) and
      in the evening (between 18.00-22.00 hours). Participants were asked to report the
      subjective comfort immediately after both of these instillations, on a scale from
      1 (poor) to 10 (excellent). This was done for ambient (aAT) and refrigerated
      (rAT) drops. An in vitro study evaluated if there were any changes in eye-drop pH
      and osmolarity with refrigeration. RESULTS: Participants (n = 18, three male, 15
      female, age 22-28 years, average 24.4 +/- 1.6) reported mean comfort scores (+/-
      standard deviation) of 7.8 +/- 0.9 and 7.6 +/- 1.4, for the aAT and the rAT,
      respectively. Mean comfort scores (+/- standard deviation) for morning and
      evening, were 7.7 +/- 1.2 and 7.8 +/- 1.1, respectively. A non-parametric
      Friedman test of differences among repeated measures was conducted and rendered a
      chi-squared value of 3.74, which was not statistically significant (p = 0.29).
      The pH remained stable at 8.0 and the osmolality did not vary significantly with
      refrigeration. CONCLUSION: There is no advantage, with respect to patient
      perceived comfort, in refrigerating the Systane Ultra (Alcon Laboratories) AT for
      mild to moderate DE.

PMID- 29457270
TI  - Clinical and echocardiographic characteristics of patients in sinus rhythm,
      normal left ventricular function, and indeterminate diastolic function.
AB  - BACKGROUND: Diastolic dysfunction (DDFx) is the major underlying mechanism of
      heart failure with preserved left ventricular ejection fraction (EF). Yet, the
      echocardiographic diagnosis of DDFx in patients in sinus rhythm is challenging
      and up to 25% of studies have discrepant measures making assessment of DDFx
      indeterminate. We aimed to describe the clinical and echocardiographic
      characteristics of patients with indeterminate diastolic function compared to
      patients with definite normal and abnormal diastolic function. METHODS: One
      thousand six hundred seventy-four patients were identified from the
      echocardiography database in sinus rhythm, EF >= 45% without wall-motion
      abnormalities, valvular, congenital heart diseases, cardiomyopathies or pulmonary
      disease. Patients were divided according to their lateral mitral E/E' ratio and
      left atrial systolic diameter: normal diastolic function (DFx) (left atrial
      systolic diameter [LASd] <40 mm, E/E' < 10), DDFx (LASd >= 40 mm, E/E' >= 10) and
      indeterminate DFx (discrepant LASd diameter and E/E' ratio). RESULTS: Clinical
      and echocardiographic characteristics of the 3 groups, DDFx (n = 186),
      indeterminate diastolic function (IndtDFx) (n = 207), and normal diastolic
      function (NDFx) (n = 1281) were significantly different. IndtDFx demonstrated
      intermediate parameter abnormalities, largely overlapping with DDFx. LASd and
      E/E' were similarly associated with the inability to determine diastolic
      function. Age, female gender, renal failure, E/E' and pulmonary pressure were
      found to be independent predictors of heart failure symptoms (RR = 1.02, 1.5,
      2.5, 1.1, 1.1, respectively, P < .0001, r = .35). CONCLUSION: Clinically and
      echocardiographically patients with IndtDFx are more closely related to DDfx than
      to NDFx. Although LAd was abnormal in IndtDFx it was not predictive of heart
      failure symptoms. Further study is suggested to establish whether LA function
      rather than its maximal size can provide additional information.

PMID- 29457272
TI  - Atopic dermatitis in diverse racial and ethnic groups-Variations in epidemiology,
      genetics, clinical presentation and treatment.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects
      diverse ethnic groups with varying prevalence. Despite a predominance of studies
      in individuals of European ancestry, AD has been found to occur more frequently
      in Asian and Black individuals than Whites. Therefore, an understanding of the
      unique clinical features of AD in diverse ethnic groups, as well as the
      differences in genetic polymorphisms that influence susceptibility to AD and
      response to current therapies, is paramount for management of an increasingly
      diverse patient population. In this article, we review key nuances in the
      epidemiology, pathophysiology, clinical presentation and treatment of AD in non
      White ethnic groups, which are largely underappreciated in the literature. We
      highlight the need for studies evaluating the tissue molecular and cellular
      phenotypes of AD in non-White patients, as well as greater inclusion of minority
      groups in clinical trials, to develop targeted treatments for a multi-ethnic
      population.

PMID- 29457273
TI  - Clinical Risk Factors for Early Seizure Recurrence in Dogs Hospitalized for
      Seizure Evaluation.
AB  - BACKGROUND: Epileptic seizures are a common cause for neurological evaluations in
      dogs. HYPOTHESIS/OBJECTIVES: To determine the timing, frequency, and risk factors
      for early seizure recurrence (ESR) among dogs admitted to the hospital for
      seizure evaluation and to facilitate rapid decision making about whether dogs
      should be placed in the intensive care unit (ICU) or day ward. ANIMALS: Nine
      hundred twenty-two dogs referred for seizure investigation; 214 patients were
      included. METHODS: Retrospective study. Medical records between 2000 and 2017
      were reviewed to determine risk factors for ESR. Findings were compared among
      dogs diagnosed with idiopathic epilepsy (IE), structural epilepsy (StE) and
      reactive seizures (RS), as well as in all selected cases together. RESULTS: Fifty
      percent of dogs had a seizure while hospitalized. In the group 53.1 and 52.2% in
      the StE group, whereas in the RS 40.44% had ESR. The average time to ESR was 7
      hours. In IE group, abnormal postictal neurological examination with
      prosencephalon signs predicted ESR. In StE group, a single generalized or focal
      seizure 72 hours before hospital admission and abnormal neurologic examination
      predicted ESR. In the RS group, ERS was predicted by long-term antiepileptic
      monotheraphy. When all dogs were analyzed together, abnormal neurological
      examination, the occurrence of cluster seizures, status epilepticus, or
      combination of them 72 hours before presentation predicted ESR. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Epileptic seizures recurred in 50% of patients within a mean
      time of 7 hours. In general, when cluster seizures, status epilepticus or both
      occurred 72 hours before presentation and neurological examination was abnormal
      upon presentation, the dog should be placed in ICU for observation.

PMID- 29457275
TI  - Re: Impact of metabolic syndrome on early recovery of continence after robot
      assisted radical prostatectomy.

PMID- 29457274
TI  - Impact of the kidney allocation system on young pediatric recipients.
AB  - The kidney allocation system (KAS) altered pediatric candidate prioritization. We
      determined KAS's impact on pediatric kidney recipients by examining delayed graft
      function (DGF) rates from 2010 to 2016. A propensity score-matched pediatric
      recipients pre- and post-KAS. A semiparametric decomposition analysis estimated
      the contributions of KAS-related changes in donor characteristics and dialysis
      time on DGF rate. The unadjusted odds of DGF were 69% higher post-KAS for young
      (<10 years at listing) recipients (N = 1153, P = .02) but were not significantly
      increased for older pediatric (10-17 years at listing) recipients (N = 2624, P =
      .48). Post-KAS, young recipients received significantly fewer pediatric (<18
      years) donor kidneys (21% vs 32%, P < .01) and had longer median pretransplant
      dialysis time (603 vs 435 days, P < .01). After propensity score matching, post
      KAS status increased the odds of DGF in young recipients 71% (OR 1.71, 95% CI
      1.01-2.46). In decomposition analysis, 24% of the higher DGF rate post-KAS was
      attributable to donor characteristics and 19% to increased recipient dialysis
      time. In a confirmatory survival analysis, DGF was associated with a 2.2 times
      higher risk of graft failure (aHR2.28, 95% CI 1.46-3.54). In conclusion, KAS may
      lead to worse graft survival outcomes in children. Allocation changes should be
      considered.

PMID- 29457276
TI  - Abrus agglutinin stimulates BMP-2-dependent differentiation through autophagic
      degradation of beta-catenin in colon cancer stem cells.
AB  - Eradicating cancer stem cells (CSCs) in colorectal cancer (CRC) through
      differentiation therapy is a promising approach for cancer treatment. Our
      retrospective tumor-specimen analysis elucidated alteration in the expression of
      bone morphogenetic protein 2 (BMP-2) and beta-catenin during the colon cancer
      progression, indicating that their possible intervention through "forced
      differentiation" in colon cancer remission. We reveal that Abrus agglutinin (AGG)
      induces the colon CSCs differentiation, and enhances sensitivity to the
      anticancer therapeutics. The low dose AGG (max. dose = 100 ng/mL) decreased the
      expression of stemness-associated molecules such as CD44 and beta-catenin in the
      HT-29 cell derived colonospheres. Further, AGG augmented colonosphere
      differentiation, as demonstrated by the enhanced CK20/CK7 expression ratio and
      induced alkaline phosphatase activity. Interestingly, the AGG-induced expression
      of BMP-2 and the AGG-induced differentiation were demonstrated to be critically
      dependent on BMP-2 in the colonospheres. Similarly, autophagy-induction by AGG
      was associated with colonosphere differentiation and the gene silencing of BMP-2
      led to the reduced accumulation of LC3-II, suggesting that AGG-induced autophagy
      is dependent on BMP-2. Furthermore, hVps34 binds strongly to BMP-2, indicating a
      possible association of BMP-2 with the process of autophagy. Moreover, the
      reduction in the self-renewal capacity of the colonospheres was associated with
      AGG-augmented autophagic degradation of beta-catenin through an interaction with
      the autophagy adaptor protein p62. In the subcutaneous HT-29 xenograft model, AGG
      profoundly inhibited the growth of tumors through an increase in BMP-2 expression
      and LC3-II puncta, and a decrease in beta-catenin expression, confirming the
      antitumor potential of AGG through induction of differentiation in colorectal
      cancer.

PMID- 29457277
TI  - Polymorphisms of CYP27B1 are associated with IFN efficacy in HBeAg-positive
      patients.
AB  - BACKGROUND: Host single nucleotide polymorphisms were associated with antiviral
      therapy in CHB patients. The CYP27B1 gene, encoding 25(OH)D3 -1alpha hydroxylase,
      might activate 25(OH)D3 to 1,25(OH)2 D3 in kidney resulted in influencing the
      efficacy of interferon (IFN). The aim of the study was to investigate the
      association between CYP27B1 polymorphisms and the response to IFN in HBeAg
      positive patients. METHODS: Eighty-seven HBeAg-positive CHB patients infected
      with HBV genotype B or C were included in the study. All patients were treated
      with IFN at least 1 year. According to the response to PEG-IFN therapy, they were
      divided into three groups: 16 complete responses (CR), 42 partial responses (PR),
      and 29 nonresponses (NR). Sanger-sequencing was utilized to genotype the CYP27B1
      SNPs(rs4646536 and rs10877012). RESULTS: In logistic regression analysis, the
      frequency of rs4646536 CC genotype was observed to be higher in the NR group.
      Besides, the GG genotype of rs10877012 differed significantly among the three
      groups. The GG genotype was prevalent in patients with CR, and patients with TT
      genotype result in NR at the end of IFN treatment. The most common haplotype TG
      was independently associated with CR, after adjustment, and haplotype CT appeared
      to be associated with NR and PR, rather than CR. The data also showed that
      patients with baseline 1,25(OH)2 D3 > 39.39 pg/mL had higher CR rates at the end
      of IFN therapy. CONCLUSION: These results suggested CYP28B1 gene polymorphisms
      may be independently associated with the efficacy of IFN in HBeAg-positive
      patients.

PMID- 29457278
TI  - Zwitterionic Nanocages Overcome the Efficacy Loss of Biologic Drugs.
AB  - For biotherapeutics that require multiple administrations to fully cure diseases,
      the induction of undesirable immune response is one common cause for the failure
      of their treatment. Covalent binding of hydrophilic polymers to proteins is
      commonly employed to mitigate potential immune responses. However, while this
      technique is proved to partially reduce the antibodies (Abs) reactive to
      proteins, it may induce Abs toward their associated polymers and thus result in
      the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown
      to improve the immunologic properties of proteins without inducing any
      antipolymer Abs against itself. However, it is unclear if the improved
      immunologic profiles can translate to better clinical outcomes since improved
      immunogenicity cannot directly reflect amelioration in efficacy. Here, a PCB
      nanocage (PCB NC) is developed, which can physically encase proteins while
      keeping their structure intact. PCB NC encapsulation of uricase, a highly
      immunogenic enzyme, is demonstrated to eradicate all the immune responses. To
      bridge the gap between immunogenicity and efficacy studies, the therapeutic
      performance of PCB NC uricase is evaluated and compared with its PEGylated
      counterpart in a clinical-mimicking gouty rat model to determine any loss of
      efficacy evoked after five administrations.

PMID- 29457279
TI  - Lysophosphatidylserine suppression of T-cell activation via GPR174 requires
      Galphas proteins.
AB  - G protein-coupled receptors regulate diverse aspects of T-cell activity and
      effector function. Recently, we showed that GPR174 mediates the suppression of T
      cell proliferation in vitro induced by the polar lipid lysophosphatidylserine
      (LysoPS). Here, we investigated the in vivo activity of this pathway and
      characterized the mechanisms involved. Using in vivo models of T-cell
      proliferation induced by sublethal irradiation or regulatory T-cell depletion, we
      show that GPR174 expression can constrain T-cell proliferation. In vitro
      experiments established that Galphas G proteins are needed for LysoPS/GPR174
      mediated suppression of T-cell proliferation. Mechanistically, LysoPS acts via
      GPR174 and Galphas to suppress IL-2 production by activated T cells and limit
      upregulation of the activation markers CD25 and CD69. Together, our findings
      identify GPR174 as an abundantly expressed Galphas-dependent receptor that can
      negatively regulate naive T-cell activation. See also: News and Commentary by
      Robert & Mackay.

PMID- 29457280
TI  - Continuous blood purification ameliorates clinical signs and corrects the plasma
      phospholipid levels of patients with multiple organ dysfunction syndromes.
AB  - BACKGROUND: Multiple organ dysfunction syndromes (MODS) is reported as a leading
      cause of mortality in intensive care units. Recently, continuous blood
      purification (CBP) has been mostly applied for MODS treatment. Thus, the purpose
      of this study was to investigate the effects of CBP on plasma phospholipid level
      in patients with MODS. METHODS: A total of 126 patients with MODS and 120 healthy
      people were collected. The serum cytokine levels, blood biochemical parameters,
      and blood gas indexes were detected, and the correlation among phospholipid
      compounds with serum cytokine levels, blood biochemical parameters, and blood gas
      indexes was analyzed. RESULTS: Before CBP, levels of body temperature, RR, HR,
      CVP, IL-6, IL-10, TNF-alpha, BUN, SCr, PaCO2 , SM747, and LPC540 were obviously
      higher, and pH, HCO3- , PaO2 , SaO2 , PE750, PI885, PC792, PC826, PC830, PC854,
      PC802, and PG747 were lower in the MODS group than those in the control group.
      During CBP, the MODS group had gradually declined RR, CVP, levels of IL-6, IL-10
      and TNF-alpha, BUN, SCr, PaCO2 , SM747, and LPC540 and increased HCO3- , PaO2 and
      SaO2 , PE750, PI885, PC792, PC826, PC830, PC854, PC802, and PG747. Besides,
      levels of PE750, PI885, PC792, PC826, PC830, PC854, PC802, and PG747 had an
      obvious negative correlation with levels of TNF-alpha, IL-10, IL-6, BUN, SCr, and
      PaCO2 , and a significant positive correlation with levels of HCO3- , PaO2 , and
      SaO2 . CONCLUSION: CBP could effectively ameliorate clinical signs of patients
      with MODS and correct the plasma phospholipid levels.

PMID- 29457281
TI  - Vitrimer Elastomer-Based Jigsaw Puzzle-Like Healable Triboelectric Nanogenerator
      for Self-Powered Wearable Electronics.
AB  - Functional polymers possess outstanding uniqueness in fabricating intelligent
      devices such as sensors and actuators, but they are rarely used for converting
      mechanical energy into electric power. Here, a vitrimer based triboelectric
      nanogenerator (VTENG) is developed by embedding a layer of silver nanowire
      percolation network in a dynamic disulfide bond-based vitrimer elastomer. In
      virtue of covalent dynamic disulfide bonds in the elastomer matrix, a thermal
      stimulus enables in situ healing if broken, on demand reconfiguration of shape,
      and assembly of more sophisticated structures of VTENG devices. On rupture or
      external damage, the structural integrity and conductivity of VTENG are restored
      under rapid thermal stimulus. The flexible and stretchable VTENG can be scaled up
      akin to jigsaw puzzles and transformed from 2D to 3D structures. It is
      demonstrated that this self-healable and shape-adaptive VTENG can be utilized for
      mechanical energy harvesters and self-powered tactile/pressure sensors with
      extended lifetime and excellent design flexibility. These results show that the
      incorporation of organic materials into electronic devices can not only bestow
      functional properties but also provide new routes for flexible device
      fabrication.

PMID- 29457282
TI  - A Simple, General Synthetic Route toward Nanoscale Transition Metal Borides.
AB  - Most nanomaterials, such as transition metal carbides, phosphides, nitrides,
      chalcogenides, etc., have been extensively studied for their various properties
      in recent years. The similarly attractive transition metal borides, on the
      contrary, have seen little interest from the materials science community, mainly
      because nanomaterials are notoriously difficult to synthesize. Herein, a simple,
      general synthetic method toward crystalline transition metal boride nanomaterials
      is proposed. This new method takes advantage of the redox chemistry of Sn/SnCl2 ,
      the volatility and recrystallization of SnCl2 at the synthesis conditions, as
      well as the immiscibility of tin with boron, to produce crystalline phases of 3d,
      4d, and 5d transition metal nanoborides with different morphologies (nanorods,
      nanosheets, nanoprisms, nanoplates, nanoparticles, etc.). Importantly, this
      method allows flexibility in the choice of the transition metal, as well as the
      ability to target several compositions within the same binary phase diagram
      (e.g., Mo2 B, alpha-MoB, MoB2 , Mo2 B4 ). The simplicity and wide applicability
      of the method should enable the fulfillment of the great potential of this
      understudied class of materials, which show a variety of excellent chemical,
      electrochemical, and physical properties at the microscale.

PMID- 29457283
TI  - Direct Visualization of the Reversible O2- /O- Redox Process in Li-Rich Cathode
      Materials.
AB  - Conventional cathodes of Li-ion batteries mainly operate through an insertion
      extraction process involving transition metal redox. These cathodes will not be
      able to meet the increasing requirements until lithium-rich layered oxides emerge
      with beyond-capacity performance. Nevertheless, in-depth understanding of the
      evolution of crystal and excess capacity delivered by Li-rich layered oxides is
      insufficient. Herein, various in situ technologies such as X-ray diffraction and
      Raman spectroscopy are employed for a typical material Li1.2 Ni0.2 Mn0.6 O2 ,
      directly visualizing O- ?O- (peroxo oxygen dimers) bonding mostly along the c
      axis and demonstrating the reversible O2- /O- redox process. Additionally, the
      formation of the peroxo O?O bond is calculated via density functional theory, and
      the corresponding O?O bond length of ~1.3 A matches well with the in situ Raman
      results. These findings enrich the oxygen chemistry in layered oxides and open
      opportunities to design high-performance positive electrodes for lithium-ion
      batteries.

PMID- 29457284
TI  - Dual-Peak Absorbing Semiconducting Copolymer Nanoparticles for First and Second
      Near-Infrared Window Photothermal Therapy: A Comparative Study.
AB  - Near-infrared (NIR) light is widely used for noninvasive optical diagnosis and
      phototherapy. However, current research focuses on the first NIR window (NIR-I,
      650-950 nm), while the second NIR window (NIR-II, 1000-1700 nm) is far less
      exploited. The development of the first organic photothermal nanoagent (SPNI-II )
      with dual-peak absorption in both NIR windows and its utilization in photothermal
      therapy (PTT) are reported herein. Such a nanoagent comprises a semiconducting
      copolymer with two distinct segments that respectively and identically absorb NIR
      light at 808 and 1064 nm. With the photothermal conversion efficiency of 43.4% at
      1064 nm generally higher than other inorganic nanomaterials, SPNI-II enables
      superior deep-tissue heating at 1064 nm over that at 808 nm at their respective
      safety limits. Model deep-tissue cancer PTT at a tissue depth of 5 mm validates
      the enhanced antitumor effect of SPNI-II when shifting laser irradiation from the
      NIR-I to the NIR-II window. The good biodistribution and facile synthesis of SPNI
      II also allow it to be doped with an NIR dye for fluorescence-imaging-guided NIR
      II PTT through systemic administration. Thus, this study paves the way for the
      development of new polymeric nanomaterials to advance phototherapy.

PMID- 29457285
TI  - Vaginal isolation of beta-haemolytic Streptococcus from bitches with and without
      neonatal deaths in the litters.
AB  - The aim of the study was to identify beta-haemolytic streptococci in the vagina
      of bitches who had delivered healthy litters and bitches who had delivered
      litters in which neonatal deaths occurred. Fifty-one bitches divided into two
      groups were used. Group 1 (G1) included 28 bitches that had delivered healthy
      litters and group 2 (G2) included 23 bitches that had delivered puppies who died
      in the neonatal period. Two vaginal samples were taken, one in proestrus and the
      other at the end of gestation (EG). Beta-haemolytic Streptococcus (BS) was
      isolated from 16 bitches (57%) in G1 and from 21 bitches (91%) in G2. The
      bacteriological cultures, serological tests (Streptex(r) ) and PCR assay allowed
      identification of Streptococcus canis and Streptococcus dysgalactiae in G1 and
      G2. Ultramicroscopic studies allowed the observation of M Protein and capsules in
      strains of S. dysgalactiae and S. canis in G1 and G2. The S. canis strains
      isolated from G2 showed thicker capsules than S. canis strains isolated from G1
      (234 +/- 24.2 vs 151.23 +/- 28.93 nm; p < .001.). No differences were observed in
      capsule thickness between strains of S. dysgalactiae isolated from G1 and G2 (210
      +/- 13.54 vs 211.66 +/- 19.67 nm; p > .70). All strains of beta-haemolytic
      Streptococcus isolated were penicillin sensitive. Penicillin was administered
      from EG to 5 days post-partum in 10 G2 females with isolation of BS (G2A). Saline
      solution was administered in eleven G2 females with isolation of BS (G2B). Ninety
      per cent of the puppies survived in G2A and 25% survived in G2B. Our results
      suggest BS is involved in canine neonatal deaths.

PMID- 29457286
TI  - Applicability of low-flow atmospheric pressure chemical ionization and
      photoionization mass spectrometry with a microfabricated nebulizer for neutral
      lipids.
AB  - RATIONALE: Mass spectrometry with atmospheric pressure chemical ionization (APCI)
      or photoionization (APPI) is widely used for neutral lipids involved in many
      fundamental processes in living organisms. Commercial APCI and APPI sources
      operate at high flow rates compatible with conventional high-performance liquid
      chromatography (HPLC). However, lipid analysis is often limited by a small amount
      of sample, which requires low flow rate separations like capillary or micro-HPLC.
      Therefore, APCI and APPI suitable for microliter-per-minute flow rates need to be
      developed and applied for neutral lipids. METHODS: A micro-APCI/APPI source with
      a heated chip nebulizer was assembled and mounted on a Thermo ion trap
      instrument. The ion source operated in APCI, APPI or dual mode was optimized for
      low microliter-per-minute sample flow rates. The source performance was
      investigated for squalene, wax esters, fatty acid methyl esters,
      triacylglycerols, and cholesterol. RESULTS: The ion source behaved as a mass-flow
      sensitive detector. Direct infusion of methyl oleate showed superior analytical
      figures of merit when compared with high-flow ion sources. A detection limit of
      200 pmol/mL and a linear dynamic range spanning three orders of magnitude were
      measured for micro-APCI. The mass spectra of most lipids differed from high flow
      rate spectra. Unlike micro-APCI, micro-APPI spectra were complicated by odd
      electron species. Dual APCI/APPI mode did not show any benefits for neutral
      lipids. Applications for lipid samples were demonstrated. CONCLUSIONS: Micro-APCI
      MS is a useful detection technique for neutral lipids at microliter-per-minute
      flow rates. It offers high sensitivity and high quality of spectra in direct
      infusion mode and promises successful utilization in capillary and micro-HPLC
      applications.

PMID- 29457287
TI  - Zero TE-based pseudo-CT image conversion in the head and its application in
      PET/MR attenuation correction and MR-guided radiation therapy planning.
AB  - PURPOSE: To describe a method for converting Zero TE (ZTE) MR images into X-ray
      attenuation information in the form of pseudo-CT images and demonstrate its
      performance for (1) attenuation correction (AC) in PET/MR and (2) dose planning
      in MR-guided radiation therapy planning (RTP). METHODS: Proton density-weighted
      ZTE images were acquired as input for MR-based pseudo-CT conversion, providing
      (1) efficient capture of short-lived bone signals, (2) flat soft-tissue contrast,
      and (3) fast and robust 3D MR imaging. After bias correction and normalization,
      the images were segmented into bone, soft-tissue, and air by means of
      thresholding and morphological refinements. Fixed Hounsfield replacement values
      were assigned for air (-1000 HU) and soft-tissue (+42 HU), whereas continuous
      linear mapping was used for bone. RESULTS: The obtained ZTE-derived pseudo-CT
      images accurately resembled the true CT images (i.e., Dice coefficient for bone
      overlap of 0.73 +/- 0.08 and mean absolute error of 123 +/- 25 HU evaluated over
      the whole head, including errors from residual registration mismatches in the
      neck and mouth regions). The linear bone mapping accounted for bone density
      variations. Averaged across five patients, ZTE-based AC demonstrated a PET error
      of -0.04 +/- 1.68% relative to CT-based AC. Similarly, for RTP assessed in eight
      patients, the absolute dose difference over the target volume was found to be
      0.23 +/- 0.42%. CONCLUSION: The described method enables MR to pseudo-CT image
      conversion for the head in an accurate, robust, and fast manner without relying
      on anatomical prior knowledge. Potential applications include PET/MR-AC, and MR
      guided RTP.

PMID- 29457288
TI  - Injury to the perineal branch of the pudendal nerve in men: Outcomes from
      surgical resection of the perineal branches.
AB  - OBJECTIVE: The objective is to report the outcome of an anterior surgical
      approach to treat neuroma of the perineal branch of the pudendal nerve (PBPN).
      PATIENTS AND METHODS: An IRB-approved prospective study enrolled 14 consecutive
      male patients from 2011 through 2015 who had symptoms of perineal/scrotal pain.
      Each patient had a successful, diagnostic, pudendal nerve block. The surgical
      procedure was resection of the PBPN and implantation of the nerve into the
      obturator internus muscle. Mean age at surgery was 50 +/- 15 years. Median
      duration of pain symptoms was 5.5 years (range 1.2-42.9 years). Mechanisms of
      injury was exercise (6/14), prostatectomy (4/14), and falls (4/14). Outcomes were
      the Male Pudendal Pain Functional Questionnaire (MQ), and the Numeric Pain Rating
      Scale (NPRS). RESULTS: The mean postoperative follow-up was 26 +/- 14 months. The
      MQ demonstrated that after surgery, patients overall had significantly less
      disability due to pudendal pain (P < .03). The NPRS revealed that pain
      significantly improved (P < .004). CONCLUSIONS: Resection of the PBPN and
      implantation of this nerve into the obturator internus muscle significantly
      relieved men's pelvic pain disability.

PMID- 29457289
TI  - Noninvasively Modifying Band Structures of Wide-Bandgap Metal Oxides to Boost
      Photocatalytic Activity.
AB  - Although doping with appropriate heteroatoms is a powerful way of increasing
      visible light absorption of wide-bandgap metal oxide photocatalysts, the
      incorporation of heteroatoms into the photocatalysts usually leads to the
      increase of deleterious recombination centers of photogenerated charge carriers.
      Here, a conceptual strategy of increasing visible light absorption without
      causing additional recombination centers by constructing an ultrathin insulating
      heterolayer of amorphous boron oxynitride on wide-bandgap photocatalysts is
      shown. The nature of this strategy is that the active composition nitrogen in the
      heterolayer can noninvasively modify the electronic structure of metal oxides for
      visible light absorption through the interface contact between the heterolayer
      and metal oxides. The photocatalysts developed show significant improvements in
      photocatalytic activity under both UV-vis and visible light irradiation compared
      to the doped counterparts by conventional doping process. These results may
      provide opportunities for flexibly tailoring the electronic structure of metal
      oxides.

PMID- 29457290
TI  - Imaging Heterogeneously Distributed Photo-Active Traps in Perovskite Single
      Crystals.
AB  - Organic-inorganic halide perovskites (OIHPs) have demonstrated outstanding energy
      conversion efficiency in solar cells and light-emitting devices. In spite of
      intensive developments in both materials and devices, electronic traps and
      defects that significantly affect their device properties remain under
      investigated. Particularly, it remains challenging to identify and to resolve
      traps individually at the nanoscopic scale. Here, photo-active traps (PATs) are
      mapped over OIHP nanocrystal morphology of different crystallinity by means of
      correlative optical differential super-resolution localization microscopy (Delta
      SRLM) and electron microscopy. Stochastic and monolithic photoluminescence
      intermittency due to individual PATs is observed on monocrystalline and
      polycrystalline OIHP nanocrystals. Delta-SRLM reveals a heterogeneous PAT
      distribution across nanocrystals and determines the PAT density to be 1.3 * 1014
      and 8 * 1013 cm-3 for polycrystalline and for monocrystalline nanocrystals,
      respectively. The higher PAT density in polycrystalline nanocrystals is likely
      related to an increased defect density. Moreover, monocrystalline nanocrystals
      that are prepared in an oxygen- and moisture-free environment show a similar PAT
      density as that prepared at ambient conditions, excluding oxygen or moisture as
      chief causes of PATs. Hence, it is concluded that the PATs come from inherent
      structural defects in the material, which suggests that the PAT density can be
      reduced by improving crystalline quality of the material.

PMID- 29457291
TI  - Does sedation offer better outcomes than local anaesthesia for thyroid FNA in
      adult patients?
AB  - OBJECTIVE: To examine the potential benefits of sedation in adults undergoing
      fine needle aspiration (FNA) of thyroid nodules. METHODS: This retrospective
      study compared the outcomes of sedated and non-sedated FNA patients. RESULTS: A
      total of 860 patients underwent 1698 FNAs of thyroid nodules. The mean patient
      age was 52.4+/-14.4 years, and 80.2% of patients were women. The non-sedated
      group consisted of 782 patients with 1543 (93.5%) FNA procedures. The sedated
      group consisted of 66 patients who underwent 107 (6.5%) FNAs. There was no
      statistical difference between these groups with respect to age, gender, nodule
      size, nodule vascularity, non-diagnostic sample rate and post FNA hematoma (P >
      .05). CONCLUSIONS: Performing FNA of thyroid nodules in adult patients under
      sedation is not associated with a higher diagnostic yield or lower bleeding rate
      when compared to local anesthesia. Sedation should be judiciously used on only
      very anxious patients due to the increased overall cost.

PMID- 29457292
TI  - Antibodies against H3 and H4 histones from the sera of HIV-infected patients
      catalyze site-specific degradation of these histones.
AB  - Histones and their posttranslational modified forms play pivotal roles in
      chromatin functioning and gene transcription. Also, histones are harmful when
      they enter the intercellular space; their administration to animals results in
      systemic inflammatory and toxic responses. Autoantibodies having enzymatic
      activities (abzymes) are the specific feature of several autoimmune and viral
      diseases. Electrophoretically homogeneous IgGs containing no canonical proteases
      were purified from sera of HIV-infected patients by using several affinity
      chromatographies. In contrast to known canonical proteases, Abs from HIV-infected
      patients hydrolyzed exclusively only histones but no other control globular
      proteins. The H3 and H4 histone cleavage sites by antihistone IgGs were
      determined by matrix-assisted laser desorption/ionization mass spectrometry for
      the first time. Two clusters of H3 hydrolysis contain major (?) and minor (*)
      cleavage sites: 18-K*Q*LA?TK*A?AR*KS?A*P-30 and 34-G*VK*KPHR*YRPGTVA*L*R-50. H4
      histone has only 1 cluster of cleavage sites containing additionally moderate (?)
      cleavage sites: 15-A?KR?HR?KVLR?D*NIQ?GIT*K-31. Sites of these histones cleavage
      correspond mainly to their known epitopes. It was surprising that most of the
      cleavage sites of histones are involved in the interaction with DNA of nucleosome
      core. Because histones act as damage-associated molecules, abzymes against H3 and
      H4 can play important role in pathogenesis of AIDs and probably other viral and
      immune diseases.

PMID- 29457293
TI  - Ginsenoside Rh2 inhibits prostate cancer cell growth through suppression of
      microRNA-4295 that activates CDKN1A.
AB  - OBJECTIVES: Ginsenoside Rh2 (GRh2) has demonstrative therapeutic effects on a
      variety of diseases, including some tumours. However, the effects of GRh2 on
      prostate cancer (PC) cell growth remain unknown, and were, thus, addressed in the
      present study. MATERIALS AND METHODS: PC3 and DU145 PC cell lines were exposed to
      GRh2. Cell proliferation was assessed in an MTT assay and by BrdU incorporation.
      Apoptosis of the cells were assessed by TUNEL staining. Total RNA was assessed by
      RT-qPCR. Protein levels were assessed by Western blotting. Bioinformatics and
      dual luciferase reporter assay were applied to determine the functional binding
      of miRNA to mRNA of target gene. RESULTS: GRh2 dose-dependently decreased PC cell
      proliferation, but did not alter cell apoptosis. Mechanistically, GRh2 dose
      dependently increased the protein, but not mRNA of a cell-cycle suppressor CDKN1A
      in PC cells, suggesting the presence of microRNA (miRNA)-mediated protein
      translation control of CDKN1A by GRh2. In all candidate miRNAs that bind to 3'
      UTR of CDKN1A, miR-4295 was specifically found to be suppressed dose-dependently
      by GRh2 in PC cells. Moreover, miR-4295 bound CDKN1A to suppress its protein
      translation. Furthermore, cell proliferation in PC cells that overexpressed miR
      4295 did not alter in response to GRh2. CONCLUSIONS: GRh2 may inhibit PC cell
      growth through suppression of microRNA-4295 that activates CDKN1A.

PMID- 29457294
TI  - Cytology of cerebrospinal fluid involvement in systemic anaplastic large-cell
      lymphoma.

PMID- 29457295
TI  - "Something that happens at home and stays at home": An exploration of the lived
      experience of young carers in Western Australia.
AB  - There are approximately 350,000 young carers in Australia, yet their experience
      is not well understood. Young carers face adversities and disenfranchisement by
      being a young person in a caring role, and the role can affect other areas of
      their lives. We explored the lived experiences of young carers, aged 14-25 years
      (N = 13), from Western Australia through in-depth semi-structured interviews. A
      phenomenological approach was adopted. A thematic analysis of the transcribed
      interview data revealed four key themes. "Lessons from the experience"
      articulates the perceived benefits of the role and the themes: "navigating
      competing demands," "desire for normalcy" and "lost in the system" capture the
      struggles and complexities associated with being a young carer. Although there
      are challenges to being a young carer, it is something that young carers report
      can be beneficial and something that is done for those they love.

PMID- 29457296
TI  - Silk and Silk-Like Supramolecular Materials.
AB  - Silk is a source of marvel for centuries as one of nature's high-performance
      materials. More recently, chemical and structural analysis techniques have helped
      explore the relationship between silk's properties and its hierarchical
      structure. Furthermore, recombinant protein engineering as well as polymer and
      organic synthesis techniques have enabled the production of silk-like materials.
      It has become apparent that silk is a supramolecular polymer with many of the
      properties exhibited by well-known synthetic supramolecular materials, such as
      block copolymers, liquid crystals, thermoplastic elastomers, and self-assembling
      peptides. In this review, the hierarchical structure and supramolecular assembly
      of silk are discussed in comparison to these synthetic supramolecular systems. By
      focusing on the connections between chemical structure, nanoscale molecular
      organization, and material properties, the aim is to provide perspectives on the
      rational design of advanced soft matter to supramolecular chemists and molecular
      engineers who look to nature for inspiration.

PMID- 29457297
TI  - The impact of bacteriophages on phyllosphere bacterial abundance and composition.
AB  - Interactions between bacteria and bacteriophage viruses (phages) are known to
      influence pathogen growth and virulence, microbial diversity and even
      biogeochemical cycling. Lytic phages in particular infect and lyse their host
      cells, and can therefore have significant effects on cell densities as well as
      competitive dynamics within microbial communities. Despite the known impacts of
      lytic phages on the ecology and evolution of bacteria in free-living communities,
      little is known about the role of lytic phages in host-associated microbiomes. We
      set out to characterize the impact of phages in the tomato phyllosphere, that is
      the bacteria associated with above-ground plant tissues, by transferring
      microbial communities from field-grown tomato plants to juvenile plants grown
      under mostly sterile conditions in either the presence or absence of their
      associated phage community. In three separate experiments, we found that the
      presence of phages affects overall bacterial abundance during colonization of new
      host plants. Furthermore, bacterial community analysis using 16S rRNA amplicon
      sequencing shows that phages significantly alter the relative abundance of
      dominant community members and can influence both within- and among-host
      diversity. These results underscore the importance of lytic phages in host
      associated microbiomes and are relevant to microbiome transplantation approaches,
      as they suggest transferring nonbacterial components of the microbiome among
      hosts is likely to have a strong impact on growth of both the resident and
      colonizing microbiota.

PMID- 29457298
TI  - Forest structure provides the income for reproductive success in a southern
      population of Canada lynx.
AB  - Understanding intrinsic and extrinsic drivers of reproductive success is central
      to advancing animal ecology and characterizing critical habitat. Unfortunately,
      much of the work examining drivers of reproductive success is biased toward
      particular groups of organisms (e.g., colonial birds, large herbivores, capital
      breeders). Long-lived mammalian carnivores that are of conservation concern,
      solitary, and territorial present an excellent situation to examine intrinsic and
      extrinsic drivers of reproductive success, yet they have received little
      attention. Here, we used a Canada lynx (Lynx canadensis) data set, from the
      southern periphery of their range, to determine if reproductive success in a
      solitary carnivore was consistent with capital or income breeding. We radio
      marked and monitored 36 female Canada lynx for 98 lynx years. We evaluated how
      maternal characteristics and indices of food supply (via forest structure) in
      core areas influenced variation in body condition and reproductive success. We
      characterized body condition as mass/length and reproductive success as whether a
      female produced a litter of kittens for a given breeding season. Consistent with
      life-history theory, we documented a positive effect of maternal age on body
      condition and reproductive success. In contrast to predictions of capital
      breeding, we observed no effect of pre-pregnancy body condition on reproductive
      success in Canada lynx. However, we demonstrated statistical effects of forest
      structure on reproductive success in Canada lynx, consistent with predictions of
      income breeding. The forest characteristics that defined high success included
      (1) abundant and connected mature forest and (2) intermediate amounts of small
      diameter regenerating forest. These attributes are consistent with providing
      abundant, temporally stable, and accessible prey resources (i.e., snowshoe hares;
      Lepus americanus) for lynx and reinforce the bottom-up mechanisms influencing
      Canada lynx populations. Collectively, our results suggest that lynx on the
      southern range periphery exhibit an income breeding strategy and that forest
      structure supplies the income important for successful reproduction. More
      broadly, our insights advance the understanding of carnivore ecology and serve as
      an important example on integrating long-term field studies with ecological
      theory to improve landscape management.

PMID- 29457299
TI  - T1rho mapping of articular cartilage grafts after autologous osteochondral
      transplantation for osteochondral lesions of the talus: A longitudinal
      evaluation.
AB  - BACKGROUND: Clinical results of autologous osteochondral transplantation (AOT)
      for treatment of osteochondral lesions of the talus have been mixed. T1rho
      imaging can be used to noninvasively detect early cartilage degeneration. PURPOSE
      OR HYPOTHESIS: To quantitatively assess, by means of T1rho imaging, changes over
      time in the biochemical health of grafted cartilage after AOT for osteochondral
      lesions of the talus. STUDY TYPE: Retrosepctive case series. POPULATION: The
      study group comprised nine patients who underwent AOT for an osteochondral lesion
      of the talus and in whom T1rho mapping was performed 1 and 2 years
      postoperatively. FIELD STRENGTH/SEQUENCE: 3 Tesla. T1rho-weighted turbo field
      echo. ASSESSMENT: The mean T1rho value of full-thickness cartilage at the repair
      site and that of full-thickness cartilage elsewhere in the same image (far-field
      cartilage) were determined. Clinical assessment was based on the American
      Orthopaedic Foot & Ankle Society (AOFAS) scale. Correlation between the T1rho
      ratios (grafted-to-far-field cartilage T1rho values) and clinical outcomes was
      examined. STATISTICAL TESTS: Mixed effects model. Pearson correlation analysis.
      RESULTS: At 1 year, a significant difference existed between the mean T1rho value
      of the grafted cartilage (57.0 +/- 7.7 ms) and that of the far-field cartilage
      (41.8 +/- 4.6 ms) (P < 0.001). At 2 years, the mean T1rho value of the grafted
      cartilage (49.1 +/- 6.4 ms) was significantly lower than that at 1 year (P =
      0.011). Moderate negative correlation was found between the 1-year T1rho ratio
      and 1-year AOFAS score (r = -0.60) and between the 2-year T1rho ratio and 2-year
      AOFAS score (r = -0.50). DATA CONCLUSION: Our observation of substantial
      restoration of the proteoglycan content of the grafted cartilage approximately 2
      years after AOT for osteochondral lesions of the talus indicates that the content
      changes gradually and that the cartilage reparation process is slower than
      previously believed. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. MAGN.
      RESON. IMAGING 2018;48:398-403.

PMID- 29457301
TI  - Bioconjugation with Thiols by Benzylic Substitution.
AB  - A benzylic substitution of 3-indolyl(hydroxyl)acetate derivatives with thiols
      proceeded specifically in the presence of amino, carboxy, and phosphate groups in
      weakly acidic aqueous solutions under nearly physiological condition, while no
      reaction occurred at pH over 7. Kinetic studies revealed that the reaction
      followed second-order kinetics (first-order in the reactant and first-order in
      thiol) in contrast with the SN 1 mechanism of common benzylic substitution of
      alcohols. The utility of the present method for functionalization of
      biomacromolecules was demonstrated using several model proteins, such as
      lysozyme, insulin, trypsin, and serum albumin. The catalytic bioactivity of
      lysozyme in lysis of Micrococcus lysodeikticus cells was completely retained
      after the modification.

PMID- 29457300
TI  - Glucagon-like peptide 2 decreases osteoclasts by stimulating apoptosis dependent
      on nitric oxide synthase.
AB  - OBJECTIVES: Glucagon-like peptide 2 (GLP2) is involved in the regulation of
      energy absorption and metabolism. Despite the importance of the GLP2 signalling
      mechanisms on osteoclast, little has been studied on how GLP2 works during
      osteoclastogenesis. MATERIALS AND METHODS: RAW264.7 cells were infected with rLV
      Green-GLP2. The induction of osteoclasts was performed by RANKL. TRAP were
      detected by RT-PCR, Western blotting and staining. Total nitric oxide and total
      NOS activity were measured. Cells apoptosis was detected by Hoest33258 and Annix
      V staining. Animal test, chromatin immunoprecipitation (CHIP), co
      immunoprecipitation(IP) and luciferase reporter assay were also performed.
      RESULTS: We indicate that GLP2 is associated with osteoporosis-related factors in
      aged rats, including BALP, TRAP, IL6, TNFalpha, Nitric Oxide (NO), iNOS,
      calcitonin and occludin. Moreover, GLP2 is demonstrated to result in negative
      action during proliferation of tartrate-resistant acid phosphatase-positive
      (TRAP+) osteoclasts. Furthermore, GLP2 decreases osteoclasts induced from
      monocyte/macrophage cells RAW264.7 as well as the serum TRAP activity in aged
      rats. Mechanistic investigations reveal GLP2 enhances the expression of iNOS
      through stimulating the activity of TGFbeta-Smad2/3 signalling in osteoclasts. In
      particular, inhibition of TGFbeta fully abrogates this function of GLP2 in
      osteoclasts. Strikingly, overexpression of GLP2 significantly increases the
      product of nitric oxide via iNOS which promotes apoptosis of osteoclasts by
      decreasing bcl2 or increasing caspase3. Thereby, the ability of GLP2 to regulate
      apoptosis depends on TGFbeta-Smad2/3-iNOS-NO signalling pathway since total NOS
      inhibitor L-NMMA specifically inhibits the actions by GLP2. CONCLUSIONS: GLP2
      induces apoptosis via TGFbeta-Smad2/3 signalling, which contributes to the
      inhibition of the proliferation of osteoclasts and which may provide potential
      therapeutic targets for the treatment of osteoporosis.

PMID- 29457303
TI  - Long term effects of ART: What do animals tell us?
AB  - Early stages of mammalian embryonic development are now known to be very
      sensitive to their microenvironment, with long term effects on fetal, postnatal,
      and adult health, thus extending to these early stages the concept of
      Developmental Origin of Health and Disease (DoHaD). In this scientific context,
      and with 3% of births in developed countries, safety of Assisted Reproductive
      Techniques procedures becomes a matter of concern. Besides, embryo technologies
      in domestic mammals, using huge number of embryos, do not seem to evidence heavy
      impacts on adult phenotypes. This paper first discusses what can or cannot be
      concluded from farm animal data, then develops long term effects of ART
      procedures (ovarian stimulation, in vitro fertilization and embryo culture)
      evidenced in model species (mainly mouse model). Recent literature demonstrates
      both individual and cumulative effects of each ART procedure on fetal and
      postnatal phenotypes. In a second part, because they are sources for further
      perturbations, immediate effects of ART on early embryo phenotypes at the
      cellular and molecular levels are described in both farm animals and model
      species. Mechanistic hypotheses supporting these ART induced phenotypic
      alterations are subsequently considered. Finally, taking into account
      interspecies differences in the mechanisms likely to be involved, the relevance
      of results obtained in animal models for human ART are discussed.

PMID- 29457304
TI  - 'Everyone has an agenda': Professionals' understanding and negotiation of risk
      within the Guardianship system of Victoria, Australia.
AB  - It is frequently asserted that pressures to assess and manage risk have eroded
      the therapeutic, rights-based foundation of the human services profession. Some
      argue that human service workers operate in a culture of fear in which self
      protection and blame avoidance, rather than clients' needs, primarily drive
      decision-making. In the field of Adult Guardianship, it has been suggested that
      organisational risk avoidance may be motivating applications for substitute
      decision-makers, unnecessarily curtailing clients' rights and freedoms. However,
      the absence of research examining the operation of risk within Guardianship
      decision-making inhibits verifying and responding to this very serious
      suggestion. This article draws on semi-structured interviews conducted with 10
      professionals involved in the Victorian Guardianship system, which explored how
      issues of risk are perceived and negotiated in everyday practice. Risk was found
      to be a complex and subjective construct which can present both dangers and
      opportunities for Guardianship practitioners and their clients. While a number of
      participants reported that Guardianship might sometimes operate as an avenue for
      mitigating the fear and uncertainty of risk, most participants also valued
      positive risk-taking and were willing, in their clients' interests, to challenge
      conservative logics of risk. These findings highlight the need for further
      research which examines how service providers and policy makers can create spaces
      that support open discussions around issues of risk and address practitioners'
      sense of fear and vulnerability.

PMID- 29457302
TI  - Innate lymphoid cells at the human maternal-fetal interface in spontaneous
      preterm labor.
AB  - PROBLEM: Pathological inflammation is causally linked to preterm labor and birth,
      the leading cause of neonatal morbidity and mortality worldwide. Our aims were to
      investigate whether (i) the newly described family of innate lymphoid cells
      (ILCs) was present at the human maternal-fetal interface and (ii) ILC
      inflammatory subsets were associated with the pathological process of preterm
      labor. METHODS OF STUDY: Decidual leukocytes were isolated from women with
      preterm or term labor as well as from gestational age-matched non-labor controls.
      ILCs (CD15- CD14- CD3- CD19- CD56- CD11b- CD127+ cells) and their subsets (ILC1,
      T-bet+ ILCs; ILC2, GATA3+ ILCs; and ILC3, RORgammat+ ILCs) and cytokine
      expression were identified in the decidual tissues using immunophenotyping.
      RESULTS: (i) The proportion of total ILCs was increased in the decidua parietalis
      of women with preterm labor; (ii) ILC1s were a minor subset of decidual ILCs
      during preterm and term gestations; (iii) ILC2s were the most abundant ILC subset
      in the decidua during preterm and term gestations; (iv) the proportion of ILC2s
      was increased in the decidua basalis of women with preterm labor; (v) the
      proportion of ILC3s was increased in the decidua parietalis of women with preterm
      labor; and (vi) during preterm labor, ILC3s had higher expression of IL-22, IL
      17A, IL-13, and IFN-gamma compared to ILC2s in the decidua. CONCLUSION: ILC2s
      were the most abundant ILC subset at the human maternal-fetal interface during
      preterm and term gestations. Yet, during preterm labor, an increase in ILC2s and
      ILC3s was observed in the decidua basalis and decidua parietalis, respectively.
      These findings provide evidence demonstrating a role for ILCs at the maternal
      fetal interface during the pathological process of preterm labor.

PMID- 29457305
TI  - Light-Induced Reversible Control of Ferroelectric Polarization in BiFeO3.
AB  - Manipulation of ferroic order parameters, namely (anti-)ferromagnetic,
      ferroelectric, and ferroelastic, by light at room temperature is a fascinating
      topic in modern solid-state physics due to potential cross-fertilization in
      research fields that are largely decoupled. Here, full optical control, that is,
      reversible switching, of the ferroelectric/ferroelastic domains in BiFeO3 thin
      films at room temperature by the mediation of the tip-enhanced photovoltaic
      effect is demonstrated. The enhanced short-circuit photocurrent density at the
      tip contact area generates a local electric field well exceeding the coercive
      field, enabling ferroelectric polarization switching. Interestingly, by tailoring
      the photocurrent direction, via either tuning the illumination geometry or simply
      rotating the light polarization, full control of the ferroelectric polarization
      is achieved. The finding offers a new insight into the interactions between light
      and ferroic orders, enabling fully optical control of all the ferroic orders at
      room temperature and providing guidance to design novel optoferroic devices for
      data storage and sensing.

PMID- 29457306
TI  - Functional characterization of collaterals in the human gingiva by laser speckle
      contrast imaging.
AB  - OBJECTIVE: The rate of blood flow between the various areas of the gingiva in
      resting position and under challenge is unknown. In this study, the LSCI method
      was used to map spatial and temporal changes in gingival blood flow after
      transient compression. METHODS: Horizontal, vertical, and papilla base
      compressions were applied on the attached gingiva in 21 healthy patients (13
      women, 8 men). LSCI was used to determine dynamic changes in regional blood flow
      during a five-second occlusion interval and subsequent reperfusion for twenty
      minutes. RESULTS: Resting blood flow in the attached gingiva apical to the
      papillae was higher as compared to that in the midbuccal area of the teeth.
      During short-term horizontal compression, ischemia was greater coronal than
      apical to the occlusion line. Postocclusive hyperemia was observed not only in
      the regions affected by ischemia but encompassed a wider area. Hyperemic response
      was more pronounced and prolonged in male than in female patients. CONCLUSIONS:
      Blood flow in the attached gingiva shows spatial differences. Our findings
      corroborate the apicocoronal orientation of blood circulation. Periodontal and
      papillary collaterals may have little role in the blood supply of the adjacent
      attached gingiva under physiological conditions.

PMID- 29457307
TI  - Iron and infection: An investigation of the optimal iron hypothesis in Lima,
      Peru.
AB  - OBJECTIVES: This article explores the optimal iron hypothesis through secondary
      data analysis of the association between hemoglobin levels and morbidity among
      children living in Canto Grande, a peri-urban community located on the outskirts
      of Lima, Peru. METHODS: Risk ratios were used to test whether lower iron status,
      assessed using the HemoCue B-Hemoglobin System, was associated with an increased
      relative risk of morbidity symptoms compared to iron replete status, controlling
      for infant age, sex, weight for height z-score, maternal education, and repeated
      measures in 515 infants aged 6-12 months. RESULTS: Infants with fewer current
      respiratory and diarrheal morbidity symptoms had a lower risk of low iron
      deficiency compared to participants who were iron replete (P < .10). Infants with
      fewer current respiratory infection symptoms had a statistically significant (P <
      .05) reduction in risk of moderate iron deficiency compared to infants who were
      iron replete. CONCLUSION: In this study, morbidity status was not predictive of
      iron deficient status over a six-month interval period, but nonreplete iron
      status was shown to be associated with current morbidity symptoms. These results
      support investigating iron status as an allostatic system that responds to
      infection adaptively, rather than expecting an optimal preinfection value.

PMID- 29457308
TI  - Single Carbon Fibers with a Macroscopic-Thickness, 3D Highly Porous Carbon
      Nanotube Coating.
AB  - Carbon fiber (CF) grafted with a layer of carbon nanotubes (CNTs) plays an
      important role in composite materials and other fields; to date, the applications
      of CNTs@CF multiscale fibers are severely hindered by the limited amount of CNTs
      grafted on individual CFs and the weak interfacial binding force. Here,
      monolithic CNTs@CF fibers consisting of a 3D highly porous CNT sponge layer with
      macroscopic-thickness (up to several millimeters), which is directly grown on a
      single CF, are fabricated. Mechanical tests reveal high sponge-CF interfacial
      strength owing to the presence of a thin transitional layer, which completely
      inhibits the CF slippage from the matrix upon fracture in CNTs@CF fiber-epoxy
      composites. The porous conductive CNTs@CF hybrid fibers also act as a template
      for introducing active materials (pseudopolymers and oxides), and a solid-state
      fiber-shaped supercapacitor and a fiber-type lithium-ion battery with high
      performances are demonstrated. These CNTs@CF fibers with macroscopic CNT layer
      thickness have many potential applications in areas such as hierarchically
      reinforced composites and flexible energy-storage textiles.

PMID- 29457309
TI  - Severe intestinal malabsorption associated with ACE inhibitor or angiotensin
      receptor blocker treatment. An observational cohort study in Germany and Italy.
AB  - PURPOSE: The angiotensin II receptor blocker (ARB) olmesartan has been recently
      associated with sprue-like enteropathy (SLE), a gastrointestinal condition
      characterized by intestinal malabsorption (IM) and severe diarrhea. Whether the
      increased risk of SLE is substance-specific or a class effect involving all ARBs
      is uncertain. The aim of this study is to assess the risk of enteropathy
      associated with ARBs and angiotensin converting enzyme inhibitors (ACE-i) by
      using data from large administrative and claim databases. METHODS: We obtained
      data from Italian local health-care units and a large German claim database and
      included patients treated with olmesartan, other ARBs, and ACE-i. In the absence
      of a specific diagnosis code for SLE, International Classification of Diseases
      codes for IM were used. Analysis implemented a Poisson regression with robust
      error variance procedure, which allowed accounting for different clusters (local
      health-care units and countries) and correctly estimating the standard error for
      the relative risk of rare event occurrence. RESULTS: Patients were divided into 3
      groups: olmesartan (25.591, 5.5%), other ARBs (104.901, 22.5%), and ACE-i
      patients (334.951, 72.0%). Baseline characteristics were similar overall. The
      incidence of unspecified IM in ACE-i patients was not different compared with
      that of olmesartan, whereas a higher rate ratio was observed when comparing ARB
      patients with the olmesartan group (RR: 2.50, 95% CI 1.21 to 5.19, P .01). When
      International Classification of Diseases codes for coeliac disease were included,
      no differences were observed. CONCLUSIONS: We could not confirm previous findings
      of a higher risk of malabsorption in olmesartan-only patients, and drug-induced
      enteropathy should be considered the result of exposure to the class of ARBs
      rather than a specific drug-related effect.

PMID- 29457311
TI  - Bicuspid Axial Wall Height Effect on CAD/CAM Crown Fracture Mode on Preparations
      Containing Advanced Total Occlusal Convergence.
AB  - PURPOSE: To evaluate bicuspid axial wall height effect on the fracture mode of
      adhesively luted, all-ceramic CAD/CAM crowns with a 20 degrees  total occlusal
      convergence (TOC). MATERIALS AND METHODS: Recently extracted premolars were
      randomly divided into 4 groups (n = 12) with all-ceramic crown preparations
      accomplished using a high-speed handpiece inserted into a milling device.
      Specimens were prepared containing occlusogingival axial wall heights of 3, 2,
      and 1 mm as well as a group containing a flat preparation surface with no axial
      wall height. All preparations contained a 20 degrees  TOC. Completed preparation
      surface area was determined, and preparation features confirmed using a digital
      measuring microscope. Scanned preparations (CEREC) were fitted with milled and
      crystallized lithium disilicate full coverage restorations and luted with a self
      etching adhesive resin cement after hydrofluoric acid etching and silanation. All
      manufacturer recommendations were followed. Specimens were stored at 37 degrees
      C/98% humidity for 24 hours. Specimens were tested to failure at a 45 degrees 
      angle to the long axis of the tooth root on a universal testing machine. Failure
      load was converted to MPa using the available bonding surface area with mean data
      analyzed using Kruskal-Wallis/Dunn's (p = 0.05) RESULTS: The 3 mm preparation
      height specimens were similar to the 2 mm specimens, and both demonstrated
      significantly stronger failure load than the 1 mm axial wall height and flat
      preparation specimens. The flat preparation and 1 mm axial wall height specimens
      all failed adhesively, while the 2 mm and 3 mm specimens failed largely due to
      tooth fracture. CONCLUSIONS: Further evidence is provided that CAD/CAM adhesive
      techniques may compensate for less than ideal preparation features. Under the
      conditions of this study, bicuspid preparations with a 20 degrees  TOC restored
      with adhesively luted, CAD/CAM e.max CAD crowns require at least 2 mm of axial
      wall height, but further planned fatigue studies are necessary before definitive
      recommendations can be made.

PMID- 29457310
TI  - Natural fruits, flowers, honey, and honeybees harbor Helicobacter pylori-positive
      yeasts.
AB  - BACKGROUND: For controlling Helicobacter pylori infection in humans, its
      environmental reservoir should be determined. In this study, yeast isolates from
      an isolated village in Iran were studied for the intracellular occurrence of H.
      pylori. MATERIALS AND METHODS: In this study, yeasts were isolated from 29
      samples, including oral swabs from villagers (n = 7), flowers and fruits (n = 6),
      honey and honeybees (n = 12) and miscellaneous samples (4). Yeasts were
      classified into 12 RFLP groups and identified by amplification of 26S rDNA and
      sequencing. DNA extracted from the yeast cells was examined for the presence of
      H. pylori using PCR. RESULTS: Of the 29 yeasts, 27 were members of different
      genera of Ascomycete. H. pylori was detected in 5 of 9 Candida (55.5%), 4 of 5
      Komagataella (80%), 3 of 4 Pichia (100%), 2 of 2 Cytobasidia (100%), 2 of 2
      Hansenia (100%), 1 of 1 Meyerozyma (100%) and 2 of 3 not sequenced (66.6%)
      yeasts. Distribution of 19 of 29 (65.5%) H. pylori-positive yeasts within 4
      groups was as follows: 1 of 7(14.3%) in oral swabs, 5 of 6 (83.3%) in flowers and
      fruits, 10 of 12 (83.3%) in honey and the bee group and 3 of 4 (75%) in
      miscellaneous. CONCLUSIONS: Different genera of osmotolerant yeasts from flowers,
      fruits, honey, and honeybees contained H. pylori in their vacuole. High frequency
      of H. pylori-positive yeasts in these samples might be related to their high
      sugar content. Insects such as honeybees that facilitate transfer and easy access
      of these yeasts to nectars serve as the main reservoirs of these yeasts, playing
      an important role in their protection and dispersal. Accordingly, H. pylori
      inside these yeasts can be carried by honeybees to different sugar- and nutrient
      rich environments. Sugar-rich environments and honeybees play an important role
      in distribution of H. pylori-positive yeasts in nature.

PMID- 29457312
TI  - Update on tuberculosis biomarkers: From correlates of risk, to correlates of
      active disease and of cure from disease.
AB  - Tuberculosis (TB) remains a devastating disease, yet despite its enormous toll on
      global health, tools to control TB are insufficient and often outdated. TB
      Biomarkers (TB-BM) would constitute extremely useful tools to measure infection
      status and predict outcome of infection, vaccination or therapy. There are
      several types of TB-BM: Correlate of Infection; Correlate of TB Disease;
      Correlate of Increased Risk of Developing Active TB Disease; Correlate of the
      Curative Response to Therapy; and Correlate of Protection (CoP). Most TB-BM
      currently studied are host-derived BM, and consist of transcriptomic, proteomic,
      metabolomic, cellular markers or marker combinations ('signatures'). In
      particular, vaccine-inducible CoP are expected to be transformative in developing
      new TB vaccines as they will de-risk vaccine research and development (R&D) as
      well as human testing at an early stage. In addition, CoP could also help
      minimizing the need for preclinical studies in experimental animals. Of key
      importance is that TB-BM are tested and validated in different well-characterized
      human TB cohorts, preferably with complementary profiles and geographically
      diverse populations: genetic and environmental factors such as (viral)
      coinfections, exposure to non-tuberculous mycobacteria, nutritional status,
      metabolic status, age (infants vs children vs adolescents vs adults) and other
      factors impact host immune set points and host responses across different
      populations. In this study, we review the most recent advances in research into
      TB-BM for the diagnosis of active TB, risk of TB development and treatment
      induced TB cure.

PMID- 29457313
TI  - Modeling the hematocrit distribution in microcirculatory networks: A quantitative
      evaluation of a phase separation model.
AB  - OBJECTIVE: Theoretical models are essential tools for studying microcirculatory
      function. Recently, the validity of a well-established phase separation model was
      questioned and it was claimed that it produces problematically low hematocrit
      predictions and lack of red cells in small diameter vessels. We conducted a
      quantitative evaluation of this phase separation model to establish common ground
      for future research. METHODS: Model predictions were validated against a
      comprehensive database with measurements from 4 mesenteric networks. A Bayesian
      data analysis framework was used to integrate measurements and network model
      simulations into a combined analysis and to model uncertainties related to
      network boundary conditions as well as phase separation model parameters. The
      model evaluation was conducted within a cross-validation scheme. RESULTS: Unlike
      the recently reported results, our analysis demonstrated good correspondence in
      global characteristics between measurements and predictions. In particular,
      predicted hematocrits for vessels with small diameters were consistent with
      measurements. Incorporating phase separation model parameter uncertainties
      further reduced the hematocrit validation error by 17% and led to the absence of
      red-cell-free segments. Corresponding model parameters are presented as
      alternatives to standard parameters. CONCLUSIONS: Consistent with earlier
      studies, our quantitative model evaluation supports the continued use of the
      established phase separation model.

PMID- 29457314
TI  - Latent source mining in FMRI via restricted Boltzmann machine.
AB  - Blind source separation (BSS) is commonly used in functional magnetic resonance
      imaging (fMRI) data analysis. Recently, BSS models based on restricted Boltzmann
      machine (RBM), one of the building blocks of deep learning models, have been
      shown to improve brain network identification compared to conventional single
      matrix factorization models such as independent component analysis (ICA). These
      models, however, trained RBM on fMRI volumes, and are hence challenged by model
      complexity and limited training set. In this article, we propose to apply RBM to
      fMRI time courses instead of volumes for BSS. The proposed method not only
      interprets fMRI time courses explicitly to take advantages of deep learning
      models in latent feature learning but also substantially reduces model complexity
      and increases the scale of training set to improve training efficiency. Our
      experimental results based on Human Connectome Project (HCP) datasets
      demonstrated the superiority of the proposed method over ICA and the one that
      applied RBM to fMRI volumes in identifying task-related components, resulted in
      more accurate and specific representations of task-related activations. Moreover,
      our method separated out components representing intermixed effects between task
      events, which could reflect inherent interactions among functionally connected
      brain regions. Our study demonstrates the value of RBM in mining complex
      structures embedded in large-scale fMRI data and its potential as a building
      block for deeper models in fMRI data analysis.

PMID- 29457315
TI  - Testing the validity and reliability of the Self-Administration of Medication
      (SAM) instrument in Chinese chronic disease patients: A cross-cultural
      adaptation.
AB  - AIMS: To develop a culturally appropriate and functional standard Mandarin
      Chinese translation of the Self-Administration of Medication tool and to examine
      its validity and reliability. METHODS: We used Brislin's guidelines for the
      translation and back-translation procedures. We recruited 130 patients from June
      2015 to September 2016. Correlation analysis, Cronbach's alpha coefficient, split
      half reliability, item analysis and the content validity index, and exploratory
      factor analysis were performed. RESULTS: Strong and moderate correlations were
      seen between the total Self-Administration of Medication score and nurses' and
      patients' perceptions. Item analysis indicated that the correlation coefficient
      ranged from 0.744 to 0.975. Cronbach's alpha ranged from 0.933 to 0.976. The
      split-half reliability ranged from 0.911 to 0.936 for the instrument's subscales,
      and 0.953 for the total scale. The content validity index value ranged from 0.823
      to 0.972 for individual items and was 0.968 for the total scale. The factor
      loading matrix of the SAM ranged from 0.514 to 0.837. A moderate correlation
      existed between the scores of the Self-Administration of Medication tool and the
      Barthel Index. CONCLUSION: The Chinese version of the Self-Administration of
      Medication tool is statistically acceptable and can be used in the evaluation of
      self-medication ability based on self-report and nurses' assessment.

PMID- 29457317
TI  - Effects of alcohol intoxication on self-reported drinking patterns, expectancies,
      motives and personality: a randomized controlled experimental study.
AB  - Alcohol intoxication may affect self-reports of alcohol use and related
      constructs, such as impulsivity and dependence symptoms. Improved knowledge about
      potential systematic reporting biases induced by alcohol, e.g. through
      disinhibition, may be relevant for the assessment of intoxicated individuals both
      in clinical routine and research. We therefore randomly assigned 54 socially
      drinking males aged 18 to 19 without lifetime diagnosis of DSM-IV alcohol
      dependence to one of two experimental arms: either placebo infusion at day 1 and
      alcohol infusion at day 2, or vice versa. The lab-based intravenous alcohol
      infusion produced a constant blood alcohol level of 0.08 percent. On each day,
      participants completed the Alcohol Use Disorders Identification Test, as well as
      other questionnaires on alcohol expectancies, drinking motives and substance use
      related temperament traits. We found that alcohol significantly increased self
      reported expectancies (tension reduction) and motives (conformity; eta2  = .16
      .23), but we observed no effect of sequence, i.e. alcohol first versus placebo
      first (Pcorr  >= .118). High baseline alcohol expectancies did not moderate
      alcohol effects (Pcorr  >= .462). We conclude that moderate alcohol intoxication
      might not generally affect the reliability of self-reported alcohol use, alcohol
      use problems and psychological concepts related to drinking behavior in young
      males without alcohol dependence. Future studies could examine larger, less
      selective and clinical samples for possible alcohol effects on self-report
      measures related to alcohol consumption.

PMID- 29457316
TI  - Assessment of pulmonary structure-function relationships in young children and
      adolescents with cystic fibrosis by multivolume proton-MRI and CT.
AB  - BACKGROUND: Lung disease is the most frequent cause of morbidity and mortality in
      patients with cystic fibrosis (CF), and there is a shortage of sensitive
      biomarkers able to regionally monitor disease progression and to assess early
      responses to therapy. PURPOSE: To determine the feasibility of noncontrast
      enhanced multivolume MRI, which assesses intensity changes between expiratory and
      inspiratory breath-hold images, to detect and quantify regional ventilation
      abnormalities in CF lung disease, with a focus on the structure-function
      relationship. STUDY TYPE: Retrospective. POPULATION: Twenty-nine subjects,
      including healthy young children (n = 9, 7-37 months), healthy adolescents (n =
      4, 14-22 years), young children with CF lung disease (n = 10, 7-47 months), and
      adolescents with CF lung disease (n = 6, 8-18 years) were studied. FIELD
      STRENGTH/SEQUENCE: 3D spoiled gradient-recalled sequence at 1.5T. ASSESSMENT:
      Subjects were scanned during breath-hold at functional residual capacity (FRC)
      and total lung capacity (TLC) through noncontrast-enhanced MRI and CT. Expiratory
      inspiratory differences in MR signal-intensity (Delta1 H-MRI) and CT-density
      (DeltaHU) were computed to estimate regional ventilation. MR and CT images were
      also evaluated using a CF-specific scoring system. STATISTICAL TESTS: Quadratic
      regression, Spearman's correlation, one-way analysis of variance (ANOVA).
      RESULTS: Delta1 H-MRI maps were sensitive to ventilation heterogeneity related to
      gravity dependence in healthy lung and to ventilation impairment in CF lung
      disease. A high correlation was found between MRI and CT ventilation maps (R2  =
      0.79, P < 0.001). Globally, Delta1 H-MRI and DeltaHU decrease with increasing
      morphological score (respectively, R2  = 0.56, P < 0.001 and R2  = 0.31, P <
      0.001). Locally, Delta1 H-MRI was higher in healthy regions (median 15%) compared
      to regions with bronchiectasis, air trapping, consolidation, and to segments fed
      by airways with bronchial wall thickening (P < 0.001). DATA CONCLUSION:
      Multivolume noncontrast-enhanced MRI, as a nonionizing imaging modality that can
      be used on nearly any MRI scanner without specialized equipment or gaseous
      tracers, may be particularly valuable in CF care, providing a new imaging
      biomarker to detect early alterations in regional lung structure-function. LEVEL
      OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:531
      542.

PMID- 29457318
TI  - Equity dimensions of the availability and quality of reproductive, maternal and
      neonatal health services in Zambia.
AB  - OBJECTIVE: To assess how quality and availability of reproductive, maternal,
      neonatal (RMNH) services vary by district wealth and urban/rural status in
      Zambia. METHODS: We conducted a retrospective analysis of data from the
      Millennium Development Goal Acceleration Initiative baseline assessment of 117
      health facilities in 9 districts. Quality was assessed through a composite score
      of 23 individual RMNH indicators, ranging from 0 to 1. Availability was evaluated
      by density of providers and facilities. Districts were divided into wealth groups
      based on the multidimensional poverty index (MPI). Relative inequity was
      calculated using the concentration index for quality indicators (positive favours
      rich, negative favours poor). Multivariable linear regression was performed for
      the dependent variable composite quality indicator using MPI, urban/rural, and
      facility level of care as independent variables. RESULTS: 13 hospitals, 85 health
      centres and 19 health posts were included. The RMNH composite quality indicator
      was 0.64. Availability of facilities and providers was universally low. The
      concentration index for the composite quality indicator was -0.015 [-0.043,
      0.013], suggesting no clustering to favour either rich or poor districts. Rich
      districts had the highest absolute numbers of health facilities and providers,
      but lowest numbers per facility per 1 000 000 population. Urban districts had
      slightly better service quality, but not availability. Using regression analysis,
      only facility level of care was significantly associated with quality outcome.
      CONCLUSIONS: Composite quality of RMNH services did not vary by district wealth,
      but was slightly higher in urban districts. The availability data suggest that
      the higher population in richer districts outpaces health infrastructure.

PMID- 29457320
TI  - Restoration of Facial Form and Lip Competence in a Patient with a Midfacial
      Defect.
AB  - Squamous cell carcinoma (SCC) of the head and neck can be treated with a
      combination of modalities. There is an esthetic and functional compromise with
      midfacial defects secondary to ablative surgery and adjuvant therapies for SCC.
      Osteoradionecrosis, tissue contracture, and trismus, are all negative side
      effects of treatment and can impact a patient's function and possibly their
      nutrition. In this report, we describe a procedure for fabrication of a
      prosthesis that provides cosmetic improvement and labial competence to maintain
      caloric intake.

PMID- 29457319
TI  - The impact of B1+ correction on MP2RAGE cortical T1 and apparent cortical
      thickness at 7T.
AB  - Determination of cortical thickness using MRI has often been criticized due to
      the presence of various error sources. Specifically, anatomical MRI relying on T1
      contrast may be unreliable due to spatially variable image contrast between gray
      matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Especially at ultra
      high field (>= 7T) MRI, transmit and receive B1 -related image inhomogeneities
      can hamper correct classification of tissue types. In the current paper, we
      demonstrate that residual B1+ (transmit) inhomogeneities in the T1 -weighted and
      quantitative T1 images using the MP2RAGE sequence at 7T lead to biases in
      cortical thickness measurements. As expected, post-hoc correction for the
      spatially varying B1+ profile reduced the apparent T1 values across the cortex in
      regions with low B1+, and slightly increased apparent T1 in regions with high
      B1+. As a result, improved contrast-to-noise ratio both at the GM-CSF and GM-WM
      boundaries can be observed leading to more accurate surface reconstructions and
      cortical thickness estimates. Overall, the changes in cortical thickness ranged
      between a 5% decrease to a 70% increase after B1+ correction, reducing the
      variance of cortical thickness values across the brain dramatically and
      increasing the comparability with normative data. More specifically, the cortical
      thickness estimates increased in regions characterized by a strong decrease of
      apparent T1 after B1+ correction in regions with low B1+ due to improved
      detection of the pial surface. The current results suggest that cortical
      thickness can be more accurately determined using MP2RAGE data at 7T if B1+
      inhomogeneities are accounted for.

PMID- 29457321
TI  - Wine aromatic compound production and fermentative behaviour within different non
      Saccharomyces species and clones.
AB  - AIMS: Twenty-five enological yeasts belonging to nine different species (Candida
      zeylanoides, Cryptococcus uzbekistanensis, Debaryomyces hansenii, Lachancea
      thermotolerans, Metschnikowia pulcherrima, Torulaspora delbrueckii, Williopsis
      pratensis, Zygosaccharomyces bailii and Saccharomyces cerevisiae) were screened
      for aroma formation and fermentative behaviour as part of a non-Saccharomyces
      yeast selection programme. METHODS AND RESULTS: Pure cultures were inoculated in
      pasteurized grape juice in order to perform alcoholic fermentations. Some non
      Saccharomyces species did not ferment, others did not get established and none of
      them completed alcoholic fermentations. The physico-chemical parameters of the
      wines and the abundance of aromatic compounds at the end of alcoholic
      fermentation highlighted the notable differences in the aroma-forming ability and
      fermentative behaviour of the different non-Saccharomyces species, but not within
      clones. CONCLUSIONS: Lower diversity was detected within non-Saccharomyces
      species than that reported in S. cerevisiae with regard to enological behaviour
      and aromatic profiles. Metschnikowia pulcherrima and L. thermotolerans are the
      two species with higher possibilities to become an inoculum. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Few significant differences were found within clones of the
      same species, but very important parameters in wine quality, such as volatile
      acidity, ethyl acetate and acetoin, which would justify selection programmes
      within those species. The results also demonstrated that T. delbrueckii and L.
      thermotolerans are two close species in their aromatic profiles.

PMID- 29457322
TI  - Surgical lung biopsies in elderly patients with interstitial lung disease:
      Weighing up the pros and cons.

PMID- 29457323
TI  - Anticoagulation knowledge in patients with atrial fibrillation: An Australian
      survey.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia in
      clinical practice, and is associated with a significant medical and economic
      burden. Anticoagulants reduce the risk of stroke and systemic embolism by
      approximately two-thirds compared with no therapy. Knowledge regarding
      anticoagulant therapy can influence treatment outcomes in patients with AF.
      OBJECTIVE: To measure the level of anticoagulation knowledge in patients with AF
      taking oral anticoagulants (OACs), investigate the association between patient
      related factors and anticoagulation knowledge, and compare these results in
      patients taking warfarin and direct-acting oral anticoagulant (DOACs). METHODS:
      Participants were recruited for an online survey via Facebook. Survey components
      included the Anticoagulation Knowledge Tool, the Perception of Anticoagulant
      Treatment Questionnaires (assessing treatment expectations, convenience and
      satisfaction), a modified Cancer Information Overload scale and the Morisky
      Medication Adherence Scale. Treatment groups were compared and predictors of OAC
      knowledge were identified. RESULTS: Participants taking warfarin had a higher
      knowledge score compared with those taking DOACs (n = 386, 73% +/- 13% vs 66% +/-
      14%, P<.001). Advancing age, type of OAC, health information overload and ease of
      OAC use (treatment expectation) were significant predictors of knowledge.
      Treatment expectation, including the belief that OAC treatment would cause
      bleeding side effects, varied significantly between participants taking warfarin
      and DOACs (P = .011). CONCLUSION: The study identified knowledge gaps in patients
      taking OACs, and these deficiencies appeared to be greater in participants taking
      DOACs. Knowledge assessment should be integrated into patient counselling
      sessions to help identify and resolve knowledge deficits.

PMID- 29457324
TI  - Investigation of the language tasks to include in a short-language measure for
      children in the early school years.
AB  - BACKGROUND: The inaccurate estimation of language difficulties by teachers
      suggests the benefit of a short-language measure that could be used to support
      their decisions about who requires referral to a speech-language therapist. While
      the literature indicates the potential for the development of a short-language
      measure, evidence is lacking about which combination of language tasks it should
      include. AIMS: To understand the number and nature of components/language tasks
      that should be included in a short-language measure for children in the early
      school years. METHODS & PROCEDURES: Eight language tasks were administered to
      participants of the Early Language in Victoria Study (ELVS) at ages 5 (n = 995)
      and 7 (n = 1217). These included six language tasks measured by an omnibus
      language measure (which comprised a direction-following, morphological
      completion, sentence-recall, sentence-formation, syntactic-understanding and word
      association task) and a non-word repetition and a receptive vocabulary task,
      measured by two task-specific language measures. Scores were analyzed using
      principal component analysis (PCA), the Bland and Altman method, and receiver
      operating characteristic (ROC) curve analysis. OUTCOMES & RESULTS: PCA revealed
      one main component of language that was assessed by all language tasks. The most
      effective combination of two tasks that measured this component was a direction
      following and a sentence-recall task. It showed the greatest agreement with an
      omnibus language measure and exceeded the criterion for good discriminant
      accuracy (sensitivity = 94%, specificity = 91%, accuracy = 91%, at 1 SD (standard
      deviation) below the mean). CONCLUSIONS & IMPLICATIONS: Findings support the
      combination of a direction-following and a sentence-recall task to assess
      language ability effectively in the early school years. The results could justify
      the future production of a novel short-language measure comprising a direction
      following and a sentence-recall task to use as a screening tool in schools and to
      assess language ability in research participants.

PMID- 29457325
TI  - From Linear to Angular Isomers: Achieving Tunable Charge Transport in Single
      Crystal Indolocarbazoles Through Delicate Synergetic CH/NH???pi Interactions.
AB  - Weak intermolecular interaction in organic semiconducting molecular crystals
      plays an important role in molecular packing and electronic properties. Here,
      four five-ring-fused isomers were rationally designed and synthesized to
      investigate the isomeric influence of linear and angular shapes in affecting
      their molecular packing and resultant electronic properties. Single-crystal field
      effect transistors showed mobility order of 5,7-ICZ (3.61 cm2  V-1  s-1 ) >5,11
      ICZ (0.55 cm2  V-1  s-1 ) >11,12-ICZ (ca. 10-5  cm2  V-1  s-1 ) and 5,12-ICZ (ca.
      10-6  cm2  V-1  s-1 ). Theoretical calculations based on density functional
      theory (DFT) and polaron transport model revealed that 5,7-ICZ can reach higher
      mobilities than the others thanks to relatively higher hole transfer integral
      that links to stronger intermolecular interaction due to the presence of multiple
      NH???pi and CH???pi(py) interactions with energy close to common NH???N hydrogen
      bonds, as well as overall lower hole-vibrational coupling owing to the absence of
      coupling of holes to low frequency modes due to better pi conjugation.

PMID- 29457326
TI  - Associations between adolescent risk for restrictive disordered eating and long
      term outcomes related to somatic symptoms, body mass index, and poor well-being.
AB  - OBJECTIVE: To date, no longitudinal, community-based studies have examined the
      association between disordered eating emerging in adolescence and long-term
      physical well-being. This study sought to explore the longitudinal associations
      between risk for restrictive disordered eating (DE-R; those not presenting with
      binge-purge symptoms) in adolescence and trajectories of functional somatic
      symptoms (FSS) and body mass index (BMI), and several indicators of poor physical
      well-being across early- to mid-adulthood, including medication, number of doctor
      visits, and sick leave. DESIGN: Data were obtained from the Northern Swedish
      Cohort Study (N = 1,001), a prospective longitudinal study including four time
      points from age 16 to 42 years. METHODS: A cumulative measure of DE-R risk was
      computed. Latent class growth analysis was used to identify subpopulation
      trajectories of FSS and BMI. The three-step method for auxiliary variables and
      logistic regressions were used to assess associations between DE-R and the
      trajectory classes as well as indicators of poor physical well-being. RESULTS:
      Three trajectories were identified for FSS. A gender by BMI interaction led to a
      classification of four BMI trajectories in men, but three in women. The presence
      of DE-R risk in adolescence increased odds of unfavourable FSS development,
      increasing BMI in women, and continually low BMI in men. Indicators of poor
      physical well-being at ages 21, 30, and 42 years were associated with DE-R risk
      in adolescence. CONCLUSIONS: Data spanning nearly three decades suggest that
      physical well-being impairment is related to DE-R risk measured earlier in life,
      underscoring the urgency for targeted, gender-sensitive preventive interventions
      for teenagers. Statement of contribution What is already known on this subject?
      Disordered eating is linked to poor physical and mental well-being and quality of
      life. No longitudinal studies have examined long-term physical well-being
      consequences of adolescent disordered eating risk. What does this study add? Non
      purging disordered eating symptoms in adolescence predict adverse physical well
      being outcomes in middle-aged men and women. Targeted interventions and
      preventative work during adolescence are needed.

PMID- 29457327
TI  - Electrochemical Exfoliation of Pillared-Layer Metal-Organic Framework to Boost
      the Oxygen Evolution Reaction.
AB  - Two-dimensional (2D) materials and ultrathin nanosheets are advantageous for
      elevating the catalysis performance and elucidating the catalysis mechanism of
      heterogeneous catalysts, but they are mostly restricted to inorganic or organic
      materials based on covalent bonds. We report an electrochemical/chemical
      exfoliation strategy for synthesizing metal-organic 2D materials based on
      coordination bonds. A catechol functionalized ligand is used as the redox active
      pillar to construct a pillared-layer framework. When the 3D pillared-layer MOF
      serves as an electrocatalyst for water oxidation (pH 13), the pillar ligands can
      be oxidized in situ and removed. The remaining ultrathin (2 nm) nanosheets of the
      metal-organic layers are an efficient catalyst with overpotentials as low as 211
      mV at 10 mA cm-2 and a turnover frequency as high as 30 s-1 at an overpotential
      of 300 mV.

PMID- 29457328
TI  - Cognitive performance in late adolescence and long-term risk of early heart
      failure in Swedish men.
AB  - AIMS: Heart failure (HF) incidence appears to increase among younger individuals,
      raising questions of how risk factors affect the younger population. We
      investigated the association of cognitive performance in late adolescence with
      long-term risk of early HF. METHODS AND RESULTS: We followed a cohort of Swedish
      men enrolled in mandatory military conscription in 1968-2005 (n = 1 225 300; mean
      age 18.3 years) until 2014 for HF hospitalization, using data from the Swedish
      National Inpatient Registry. Cognitive performance (IQ) was measured through a
      combination of tests, separately evaluating logical, verbal, visuospatial, and
      technical abilities. The results were standardized, weighted, and presented as
      stanines of IQ. The association between IQ and risk of HF was estimated using Cox
      proportional hazards models. In follow-up, there were 7633 cases of a first HF
      hospitalization (mean age at diagnosis 50.1 years). We found an inverse
      relationship between global IQ and risk of HF hospitalization. Using the highest
      IQ stanine as reference, the adjusted hazard ratio for the lowest IQ with risk of
      HF was 3.11 (95% confidence interval 2.60-3.71), corresponding to a hazard ratio
      of 1.32 (95% CI 1.28-1.35) per standard deviation decrease of IQ. This
      association proved persistent across predefined categories of HF with respect to
      pre-existing or concomitant co-morbidities; it was less apparent among obese
      conscripts (P for interaction =0.0004). CONCLUSION: In this study of young men,
      IQ was strongly associated with increased risk of early HF. The medical
      profession needs to be aware of this finding so as to not defer diagnosis.

PMID- 29457330
TI  - Modeling suicide in bipolar disorders.
AB  - INTRODUCTION: Suicide is a multicausal human behavior, with devastating and
      immensely distressing consequences. Its prevalence is estimated to be 20-30 times
      greater in patients with bipolar disorders than in the general population. The
      burden of suicide and its high prevalence in bipolar disorders make it imperative
      that our current understanding be improved to facilitate prediction of suicide
      and its prevention. In this review, we provide a new perspective on the process
      of suicide in bipolar disorder, in the form of a novel integrated model that is
      derived from extant knowledge and recent evidence. METHODS: A literature search
      of articles on suicide in bipolar disorder was conducted in recognized databases
      such as Scopus, PubMed, and PsycINFO using the keywords "suicide", "suicide in
      bipolar disorders", "suicide process", "suicide risk", "neurobiology of suicide"
      and "suicide models". Bibliographies of identified articles were further
      scrutinized for papers and book chapters of relevance. RESULTS: Risk factors for
      suicide in bipolar disorders are well described, and provide a basis for a
      framework of epigenetic mechanisms, moderated by neurobiological substrates,
      neurocognitive functioning, and social inferences within the environment.
      Relevant models and theories include the diathesis-stress model, the bipolar
      model of suicide and the ideation-to-action models, the interpersonal theory of
      suicide, the integrated motivational-volitional model, and the three-step theory.
      Together, these models provide a basis for the generation of an integrated model
      that illuminates the suicidal process, from ideation to action. CONCLUSION:
      Suicide is complex, and it is evident that a multidimensional and integrated
      approach is required to reduce its prevalence. The proposed model exposes and
      provides access to components of the suicide process that are potentially
      measurable and may serve as novel and specific therapeutic targets for
      interventions in the context of bipolar disorder. Thus, this model is useful not
      only for research purposes, but also for future real-world clinical practice.

PMID- 29457329
TI  - The companion dog as a model for human aging and mortality.
AB  - Around the world, human populations have experienced large increases in average
      lifespan over the last 150 years, and while individuals are living longer, they
      are spending more years of life with multiple chronic morbidities. Researchers
      have used numerous laboratory animal models to understand the biological and
      environmental factors that influence aging, morbidity, and longevity. However,
      the most commonly studied animal species, laboratory mice and rats, do not
      experience environmental conditions similar to those to which humans are exposed,
      nor do we often diagnose them with many of the naturally occurring pathologies
      seen in humans. Recently, the companion dog has been proposed as a powerful model
      to better understand the genetic and environmental determinants of morbidity and
      mortality in humans. However, it is not known to what extent the age-related
      dynamics of morbidity, comorbidity, and mortality are shared between humans and
      dogs. Here, we present the first large-scale comparison of human and canine
      patterns of age-specific morbidity and mortality. We find that many chronic
      conditions that commonly occur in human populations (obesity, arthritis,
      hypothyroidism, and diabetes), and which are associated with comorbidities, are
      also associated with similarly high levels of comorbidity in companion dogs. We
      also find significant similarities in the effect of age on disease risk in humans
      and dogs, with neoplastic, congenital, and metabolic causes of death showing
      similar age trajectories between the two species. Overall, our study suggests
      that the companion dog may be an ideal translational model to study the many
      complex facets of human morbidity and mortality.

PMID- 29457331
TI  - A strain of Streptomyces sp. isolated from rhizospheric soil of Crataegus
      oxycantha producing nalidixic acid, a synthetic antibiotic.
AB  - AIM: Exploration of microbes isolated from rhizospheric soil of Crataegus
      oxycantha for bioactive natural products. METHODS AND RESULTS: A strain of
      Streptomyces sp. (C-7) was isolated from rhizospheric soil of C. oxycantha. The
      16S rRNA gene sequence of strain C-7 displayed 99% sequence similarity with
      different Streptomyces species. The highest score was displayed for Streptomyces
      sp. strain Chy2-8 followed by Streptomyces violarus strain NBRC13104 and
      Streptomyces arenae strain ISP5293. The position of C-7 in the phylogenetic tree
      suggested uniqueness of the strain. Nalidixic acid (1), a quinolone antibiotic,
      was isolated from Streptomyces sp. strain (C-7) for the first time and
      characterized by NMR and chemically analysed. Compound 1 exhibited antimicrobial
      activity against Escherichia coli and Pseudomonas aeruginosa. The production of
      compound 1 was also validated by repeating fermentation of strain C-7 and
      compound isolation in a separate natural product laboratory with no prior
      information. Furthermore, Compound 1 showed a cytotoxic effect against human
      prostate cancer cell line PC3 with an IC50 11 MUg ml-1 . CONCLUSION: To the best
      of our knowledge, this is the first report showing production of nalidixic acid
      naturally by a strain of Streptomyces sp. SIGNIFICANCE AND IMPACT OF THE STUDY:
      In this study, we isolated a strain of Streptomyces sp. producing nalidixic acid,
      which was otherwise only obtained through chemical synthesis.

PMID- 29457332
TI  - Association of visit-to-visit blood pressure variability with the risk of all
      cause mortality and cardiovascular events in general population.
AB  - The association between blood pressure variability (BPV) and the risk of all
      cause mortality and cardiovascular diseases (CVD) is not well understood. The
      Kailuan study is a prospective longitudinal cohort study on cerebrovascular
      events and cardiovascular factors. In this study, resting blood pressure was
      measured at baseline and every 2 years from 2006 to 2007. BPV is mainly defined
      as the coefficient of variation (CV). Hazard ratio (HR), with 95% confidence
      intervals (CI) was calculated using Cox regression model. Among 52 387
      participants, we identified 1817 who ended up with all-cause death and 1198 with
      CVD. Each 4.68% increase in BPV was associated with a 13% increase in the risk of
      mortality (HR = 1.13, 95% CI = 1.09-1.18) and a 7% increase in CVD (HR = 1.07,
      95% CI = 1.02-1.13), respectively. After adjustment of confounding factors, the
      HR of comparing participants in the highest versus lowest quartile of CV of
      systolic blood pressure (SBP) was 1.37 (1.19, 1.57) for all-cause death, 1.18
      (1.01, 1.39) for CVD. Similar results were also observed when BPV was measured by
      different parameters. We concluded that visit-to-visit BPV was associated with
      all-cause death and cardiovascular and cerebrovascular events in Chinese general
      population.

PMID- 29457333
TI  - Bimatoprost sustained-release intracameral implant reduces episcleral venous
      pressure in dogs.
AB  - OBJECTIVE: To determine the effect of a bimatoprost sustained-release
      intracameral implant (Bimatoprost SR) on episcleral venous pressure (EVP) in
      normal dogs. METHODS: Normotensive beagle dogs were randomized to receive
      Bimatoprost SR 30 MUg (n = 7) or sham injection (needle insertion only, n = 7) in
      one eye on day 1. EVP was measured with an episcleral venomanometer through day
      65. Episcleral aqueous outflow vessels were identified using fluorescence imaging
      following intracameral injection of indocyanine green in one additional animal. A
      separate cohort of dogs that had been trained for conscious intraocular pressure
      (IOP) measurements received Bimatoprost SR 30 MUg (n = 8) in one eye; IOP was
      evaluated through day 66. RESULTS: Baseline mean EVP was 10.0 mmHg in the
      Bimatoprost SR group and 10.4 mmHg in the sham group. Eyes treated with
      Bimatoprost SR exhibited a transient increase in mean EVP that peaked at day 8,
      followed by a decrease to levels below baseline. From day 29 to day 65, the
      change in mean EVP from baseline ranged from -2.4 to -3.9 mmHg (P < 0.05 vs.
      sham). Baseline mean IOP in eyes treated with Bimatoprost SR was 14.9 mmHg, and a
      steady IOP reduction was maintained through day 66. Bimatoprost SR-treated eyes
      exhibited a selective, sustained dilation of aqueous outflow vessels that was not
      observed in sham-treated eyes. CONCLUSIONS: In normal dogs, Bimatoprost SR was
      associated with a transient increase in EVP followed by a sustained decrease.
      Changes in EVP were accompanied by a sustained dilation of aqueous outflow
      vessels.

PMID- 29457334
TI  - Establishing a successful perioperative geriatric service in an Australian acute
      surgical unit.
AB  - BACKGROUND: The purpose of this study was to assess the impact of a perioperative
      geriatric service (PGS) in an acute surgical unit (ASU) on patient and
      organizational outcomes. METHODS: Single centre retrospective cohort study.
      Inclusion criteria were patients over the age of 65 admitted to the ASU between
      January and June 2014 (pre-PGS) and 2015 (post-PGS). Chart reviews were performed
      to identify outcomes of interest including in-hospital morbidity and mortality,
      length of stay (LOS), 30-day representation and mortality. RESULTS: Geriatric
      admissions increased by 32% over the two study periods (154 pre-PGS and 203 post
      PGS). Surgical intervention increased by 11% (P = 0.01). Significantly more
      medical complications (14% versus 33%, P < 0.001) were identified after the
      implementation of the PGS. Recognition of delirium in the over 80s also increased
      by 57%. Rate of surgical complications was unchanged over the study (28% pre-PGS
      and 34% post-PGS, P = 0.6). In-hospital (<1%, P = 0.5) and 30-day mortality (<1%,
      P = 0.6) remained low, as did 30-day representation (10% versus 8%, P = 0.5). A
      trend towards decreased LOS of 1 day was identified after the implementation of
      the PGS (P = 0.07). CONCLUSION: This study demonstrated successful implementation
      of a PGS into an ASU. This multi-disciplinary approach has been effective in
      maintaining low numbers of surgical complications, in-hospital mortality, LOS and
      patient representations despite an increased number of medical complications.
      This likely reflects more timely recognition and intervention of medically unwell
      patients with the PGS.

PMID- 29457335
TI  - Relation of serum uric acid to an exaggerated systolic blood pressure response to
      exercise testing in men with normotension.
AB  - The authors investigated the hypothesis that high serum uric acid concentrations
      may be related to an exaggerated systolic blood pressure (SBP) response to
      maximal exercise testing in men with normotension, independent of potential
      confounding variables. In 4640 healthy men with normotension who underwent
      maximal treadmill exercise testing and fasting blood chemistry studies, including
      serum uric acid concentrations, an exaggerated SBP response, defined as SBP >=
      210 mm Hg, was detected in 152 men (3.3%). After adjusting for potential
      confounders, participants in the highest quartile of serum uric acid (>6.6 mg/dL)
      had a higher odds ratio of demonstrating an exaggerated SBP to maximal exercise
      (odds ratio, 2.19; 95% confidence interval, 1.24-3.86) compared with participants
      in the lowest quartile of serum uric acid (<5.1 mg/dL). High serum uric acid
      concentrations are associated with an exaggerated SBP response to maximal
      exercise testing in men with normotension, independent of established coronary
      risk factors.

PMID- 29457336
TI  - High school biology students use of visual molecular dynamics as an authentic
      tool for learning about modeling as a professional scientific practice.
AB  - Modeling is a practice of science that is underemphasized in biology classrooms
      in comparison to its central focus in the physical sciences. Visualizations of
      the submicroscopic world of molecules are becoming increasingly sophisticated
      with the evolution of new technologies. With this in mind, we introduced high
      school biology classrooms to a professional molecular modeling software program
      used by research biochemists to visualize proteins and other macromolecules.
      Analysis of surveys completed before and after the use of the program revealed
      significant student gains in their understandings of the nature of models.
      Student and teacher perceptions of the program showed an appreciation for the
      real/authentic nature of the program, and its affordances when utilizing the
      three-dimensional rendering of proteins. The teachers did report a general level
      of frustration regarding their lack of experience with the program and their
      inability to unlock its full potential due to not being able to access all of the
      program's features. However, we believe that the evidence at hand indicates that
      the value of introducing students to authentic molecular modeling tools in high
      school science classrooms outweighs the potential limitations. (c) 2018 by The
      International Union of Biochemistry and Molecular Biology, 46(3):230-236, 2018.

PMID- 29457337
TI  - A novel rotational matrix and translation vector algorithm: geometric accuracy
      for augmented reality in oral and maxillofacial surgeries.
AB  - BACKGROUND: Augmented reality-based surgeries have not been successfully
      implemented in oral and maxillofacial areas due to limitations in geometric
      accuracy and image registration. This paper aims to improve the accuracy and
      depth perception of the augmented video. METHODOLOGY: The proposed system
      consists of a rotational matrix and translation vector algorithm to reduce the
      geometric error and improve the depth perception by including 2 stereo cameras
      and a translucent mirror in the operating room. RESULTS: The results on the
      mandible/maxilla area show that the new algorithm improves the video accuracy by
      0.30-0.40 mm (in terms of overlay error) and the processing rate to 10-13
      frames/s compared to 7-10 frames/s in existing systems. The depth perception
      increased by 90-100 mm. CONCLUSION: The proposed system concentrates on reducing
      the geometric error. Thus, this study provides an acceptable range of accuracy
      with a shorter operating time, which provides surgeons with a smooth surgical
      flow.

PMID- 29457338
TI  - Hyperuricemia and high blood pressure at rest and during exercise: Guilty or
      innocent? The jury is still out.

PMID- 29457339
TI  - Subjective sleep quality, blood pressure, and hypertension: a meta-analysis.
AB  - Sleep quality is an important aspect of sleep, but no meta-analysis has
      elucidated its relationship with blood pressure (BP) and hypertension. A meta
      analysis was conducted in October 2016 using multiple databases, including Embase
      and Medline. Studies that assessed subjective sleep quality and BP or
      hypertension were included. Upon full-text evaluation, 29 articles from 45 041
      patients were selected, of which 22 articles were included in the meta-analysis
      and seven were presented narratively. Poor sleep quality was significantly
      associated with a greater likelihood of hypertension (odds ratio, 1.48; P value =
      .01). Poor sleepers had higher average systolic BP (mean difference = 4.37, P
      value = .09) and diastolic BP (mean difference = 1.25, P value = .32) than normal
      sleepers without statistical significance. Patients with hypertension had
      significantly worse sleep quality scores (mean difference = 1.51, P value < .01),
      while BP dippers had significantly better scores (mean difference = -1.67, P
      value < .01). The findings highlight the relationship between sleep quality and
      hypertension.

PMID- 29457340
TI  - Key Role of TFEB Nucleus Translocation for Silver Nanoparticle-Induced
      Cytoprotective Autophagy.
AB  - Transcription factor EB (TFEB) is a master regulator of autophagy and lysosomal
      biogenesis. Here, silver nanoparticles (Ag NPs)-induced cytoprotective autophagy
      required TFEB is shown. Ag NPs-induced nucleus translocation of TFEB through a
      well-established mechanism involving dephosphorylation of TFEB at serine-142 and
      serine-211 but independent of both the mTORC1 and ERK1/2 pathways. TFEB nucleus
      translocation precedes autophagy induced by Ag NPs and leads to enhanced
      expression of autophagy-essential genes. Knocking down the expression of TFEB
      attenuates the autophagy induction is demonstrated, and in the meantime, enhanced
      cell killing in HeLa cells treats with Ag NPs, indicating that TFEB is the key
      mediator for Ag NPs-induced cytoprotective autophagy. The results pinpoint TFEB
      as a potential target for developing more effective Ag NPs-based cancer
      therapeutics.

PMID- 29457341
TI  - Dietary potassium and cardiovascular profile. Results from the modification of
      diet in renal disease dataset.

PMID- 29457342
TI  - Soft tissue balancing in total knee arthroplasty using sensor-guided assessment:
      is there a learning curve?
AB  - BACKGROUND: Sensor-guided assessment for soft tissue balance in total knee
      arthroplasty (TKA) has been reported to improve patient satisfaction and self
      reported outcome scores. As more surgeons adopt this technology in TKA, we
      performed this study to identify if there is a learning curve with its use.
      METHODS: Analysis of a total of 90 consecutive cases was performed in this study.
      Initial and final intercompartmental pressure differences were recorded before
      and after knee ligament balancing. The first 45 patients (group 1) were compared
      to the last 45 patients (group 2) in terms of operative time and the final state
      of knee balance. A balanced knee was defined as pressure difference between
      medial and lateral compartments of <=15 pounds. RESULTS: Group 1 had 10
      unbalanced knees in the final pressure difference assessment, while all cases in
      group 2 were balanced (P < 0.001). There was no statistically significant
      difference in mean operative time between the two groups. A scatter plot of
      intercompartmental pressure difference identified that after 30 cases, the
      capacity to achieve knee ligament balance improved. CONCLUSION: This study
      suggests that there is a learning curve with the use of sensor-guided assessment
      in TKA in achieving knee balance; however, the differences noted between initial
      and final groups were small and may not be of clinical significance.

PMID- 29457344
TI  - Nocturnal hypertension in diabetes: Potential target of sodium/glucose
      cotransporter 2 (SGLT2) inhibition.

PMID- 29457343
TI  - Cobalt-Doped Nickel Phosphite for High Performance of Electrochemical Energy
      Storage.
AB  - Compared to single metallic Ni or Co phosphides, bimetallic Ni-Co phosphides own
      ameliorative properties, such as high electrical conductivity, remarkable rate
      capability, upper specific capacity, and excellent cycle performance. Here, a
      simple one-step solvothermal process is proposed for the synthesis of bouquet
      like cobalt-doped nickel phosphite (Ni11 (HPO3 )8 (OH)6 ), and the effect of the
      structure on the pseudocapacitive performance is investigated via a series of
      electrochemical measurements. It is found that when the cobalt content is low,
      the glycol/deionized water ratio is 1, and the reaction is under 200  degrees C
      for 20 h, the morphology of the sample is uniform and has the highest specific
      surface area. The cobalt-doped Ni11 (HPO3 )8 (OH)6 electrode presents a maximum
      specific capacitance of 714.8 F g-1 . More significantly, aqueous and solid-state
      flexible electrochemical energy storage devices are successfully assembled. The
      aqueous device shows a high energy density of 15.48 mWh cm-2 at the power density
      of 0.6 KW cm-2 . The solid-state device shows a high energy density of 14.72 mWh
      cm-2 at the power density of 0.6 KW cm-2 . These excellent performances confirm
      that the cobalt-doped Ni11 (HPO3 )8 (OH)6 are promising materials for
      applications in electrochemical energy storage devices.

PMID- 29457345
TI  - Robot-assisted vs freehand pedicle screw fixation in spine surgery - a systematic
      review and a meta-analysis of comparative studies.
AB  - BACKGROUND: Medical robotics has progressively become more compelling in modern
      orthopaedic surgery. Several studies comparing robot-assisted (RA) and freehand
      (FH) conventional techniques for pedicle screw fixation have been published, but
      the results are unclear. Here, we assessed current evidence regarding the
      efficiency, safety and accuracy of RA compared with FH techniques. METHODS: A
      literature search of PubMed, Embase, the Cochrane Library and Web of Science was
      performed to compare the differences between RA and FH in spine surgery. Two
      reviewers independently reviewed included studies, conducted a risk of bias
      assessment, and extracted data. RESULTS: Three randomized controlled trials
      (RCTs) and six retrospective comparative studies included a total of 750 patients
      (3625 pedicle screws). No significant differences were noted between RA and FH in
      pedicle screw accuracy (95.5% compared with 92.9%; odds ratio: 1.35; 95%
      confidence interval [CI], 0.55 to 3.30; P=0.51), overall complication rate (1.33%
      compared with 3.45%; odds ratio: 0.46; 95% CI, 0.15 to 1.43; P=0.18) and
      radiation exposure time (weighted mean difference [WMD]:8.49; 95% CI, -15.43 to
      32.40; P=0.49). While RA was associated with a longer operative time (WMD: 39.63;
      95% CI, 5.27 to 73.99; P= 0.02), percutaneous or minimal robot-assisted pedicle
      screw fixation (M-RA) had a shorter radiation exposure time than FH (WMD: -33.10;
      95% CI, -38.18 to -28.02; P=0.00) CONCLUSIONS: The current literature did not
      prove that RA supersedes FH, although several studies are more optimistic about
      this procedure. Future well-designed RCTs assessing RA and FH are needed to
      confirm and update the findings of this analysis.

PMID- 29457346
TI  - Dual-Hole Excitons Activated Photoelectrolysis in Neutral Solution.
AB  - II-VI semiconductors exhibit unique behaviors that can generate dual-holes
      ("heavy and light"), but the application in photocatalysis is still missing.
      Herein, an empirical utilization of light/heavy holes in a hybrid metal cluster
      2D semiconductor nanoplatelets is reported. This hybrid material can boost the
      hole-transfer at the surface and suppress the recombination. Different roles are
      enacted by light-holes and heavy-holes, in which the light-holes with higher
      energy and mobility can facilitate the slow kinetics of water oxidation and
      further reduce the onset voltage, while the massive heavy-holes can increase the
      resulting photocurrent by about five times, achieving a photocurrent of 2 mA cm-2
      at 1.23 V versus RHE under AM 1.5 G illumination in nonsacrificial neutral
      solution. These strategies can be the solutions for photoelectrolysis and be
      beneficial for sustainable development in solar conversion.

PMID- 29457348
TI  - Fixed-dose vs free-dose combinations for the management of hypertension-An
      analysis of 81 958 patients.
AB  - Fixed-dose combinations (FDC) have been developed to reduce the pill burden for
      hypertensive patients. Data on fixed-dose or free-dose (freeDC)
      ramipril/amlodipine (R/A) or candesartan/amlodipine (C/A) combination treatment
      initiation were assessed. 71 463 patients were prescribed R/A and 10 495 C/A. For
      both R/A and C/A, FDC patients were younger (both P < .001) and less comorbid.
      Prior MI (OR: 0.61 and 0.60), prior stroke (OR: 0.68 and 0.70) and CHD (OR: 0.68
      and 0.64) were negatively associated with FDC use, whereas hyperlipidemia was
      positively associated (OR: 1.26 and 1.19). Use of antihypertensive comedication
      (OR: 0.78; OR: 0.55) and treatment discontinuation within 12 months (HR: 0.65 and
      0.82) were less likely in FDC patients, who also showed superior adherence (mean
      MPR; both P < .001). Cost of the combination was higher for FDCs (both P < .001).
      FDCs improve persistence and adherence, although they are more commonly
      prescribed in patients with less cardiovascular disease.

PMID- 29457347
TI  - Comparison of the Oral Absorption, Distribution, Excretion, and Bioavailability
      of Zinc Sulfate, Zinc Gluconate, and Zinc-Enriched Yeast in Rats.
AB  - SCOPE: The oral absorption, distribution, excretion, and bioavailability of zinc
      sulfate (ZnS), zinc gluconate (ZnG), and zinc-enriched yeast (ZnY) in rats are
      fully and systemically compared for the first time. METHODS AND RESULTS: After
      zinc compounds were orally administered to rats at a single dose of 4 mg Zn kg-1
      , blood, tissues, urine, and feces at different time points were collected for
      the quantification of zinc concentration. Blood was also harvested for the zinc
      assay in the multiple-dose administration. Plasma zinc levels among three zinc
      compounds showed no difference, and zinc was widely distributed in various
      tissues with the level sequence of bone > liver > pancreas > testes. The net Zn
      balance was 2.993, 5.125, and 7.482% for ZnS, ZnG, and ZnY, respectively.
      CONCLUSION: ZnS, ZnG, and ZnY show equivalent bioavailability based on plasma and
      tissues zinc levels, although ZnY was statistically more absorbed and retained
      than ZnS and ZnG based on the excretion amount.

PMID- 29457349
TI  - Impact of Glutathione Modulation on Stability and Pharmacokinetic Profile of
      Redox-Sensitive Nanogels.
AB  - Nanoparticles degradable upon external stimuli combine pharmacokinetic features
      of both small molecules as well as large nanoparticles. However, despite
      promising preclinical results, several redox responsive disulphide-linked
      nanoparticles failed in clinical translation, mainly due to their unexpected in
      vivo behavior. Glutathione (GSH) is one of the most evaluated antioxidants
      responsible for disulfide degradation. Herein, the impact of GSH on the in vivo
      behavior of redox-sensitive nanogels under physiological and modulated conditions
      is investigated. Labelling of nanogels with a DNA-intercalating dye and a
      radioisotope allows visualization of the redox responsiveness at the cellular and
      the systemic levels, respectively. In vitro, efficient cleavage of disulphide
      bonds of nanogels is achieved by manipulation of intracellular GSH concentration.
      While in vivo, the redox-sensitive nanogels undergo, to a certain extent,
      premature degradation in circulation leading to rapid renal elimination. This
      instability is modulated by transient inhibition of GSH synthesis with
      buthioninsulfoximin. Altered GSH concentration significantly changes the in vivo
      pharmacokinetics. Lower GSH results in higher elimination half-life and altered
      biodistribution of the nanogels with a different metabolite profile. These data
      provide strong evidence that decreased nanogel degradation in blood circulation
      can limit the risk of premature drug release and enhance circulation half-life of
      the nanogel.

PMID- 29457350
TI  - Reactivating Catalytic Surface: Insights into the Role of Hot Holes in Plasmonic
      Catalysis.
AB  - Surface plasmon resonance of coinage metal nanoparticles is extensively exploited
      to promote catalytic reactions via harvesting solar energy. Previous efforts on
      elucidating the mechanisms of enhanced catalysis are devoted to hot electron
      induced photothermal conversion and direct charge transfer to the adsorbed
      reactants. However, little attention is paid to roles of hot holes that are
      generated concomitantly with hot electrons. In this work, 13 nm spherical Au
      nanoparticles with small absorption cross-section are employed to catalyze a well
      studied glucose oxidation reaction. Density functional theory calculation and X
      ray absorption spectrum analysis reveal that hot holes energetically favor
      transferring catalytic intermediates to product molecules and then desorbing from
      the surface of plasmonic catalysts, resulting in the recovery of their catalytic
      activities. The studies shed new light on the use of the synergy of hot holes and
      hot electrons for plasmon-promoted catalysis.

PMID- 29457351
TI  - 24-hour aortic blood pressure variability showed a stronger association with
      carotid damage than 24-hour brachial blood pressure variability: The SAFAR study.
AB  - We aim to compare 24-hour aortic blood pressure variability (BPV) with brachial
      BPV in relation to carotid damage as estimated by carotid intima-media thickness
      (CIMT) and cross-sectional area (CCSA). Four hundred and forty five individuals
      received brachial and aortic 24-hour ambulatory BP monitoring with a validated
      device (Mobil-O-Graph). Systolic BPV was estimated by average real variability
      (ARV) and time-weighted standard deviation (wSD). In multiple logistic regression
      analysis, CIMT > 900 MUm was significantly and independently associated with
      aortic ARV (OR = 1.38; 95% CI: 1.04-1.84), aortic wSD (OR = 1.65; 95% CI: 1.19
      2.29) and brachial ARV (OR = 1.53; 95% CI: 1.07-2.18), but not with brachial wSD.
      CCSA > 90th percentile was significantly and independently associated with aortic
      ARV (OR = 1.50; 95% CI: 1.07-2.10) and wSD (OR = 1.70; 95% CI: 1.12-2.56), but
      not with brachial BPVs. In receiver operator characteristics curve analysis,
      aortic wSD identified CCSA > 90th percentile better than brachial wSD (AUC: 0.73
      vs 0.68, P < .01). In conclusion, aortic 24-hour systolic BPV showed a slightly
      stronger association with carotid damage than brachial BPV.

PMID- 29457352
TI  - Controllable Bipolar Doping of Graphene with 2D Molecular Dopants.
AB  - The fine control of graphene doping levels over a wide energy range remains a
      challenging issue for the electronic applications of graphene. Here, the
      controllable doping of chemical vapor deposited graphene, which provides a wide
      range of energy levels (shifts up to +/- 0.5 eV), is demonstrated through
      physical contact with chemically versatile graphene oxide (GO) sheets, a 2D
      dopant that can be solution-processed. GO sheets are a p-type dopant due to their
      abundance of electron-withdrawing functional groups. To expand the energy window
      of GO-doped graphene, the GO surface is chemically modified with electron
      donating ethylene diamine molecules. The amine-functionalized GO sheets exhibit
      strong n-type doping behaviors. In addition, the particular physicochemical
      characteristics of the GO sheets, namely their sheet sizes, number of layers, and
      degree of oxidation and amine functionality, are systematically varied to finely
      tune their energy levels. Finally, the tailor-made GO sheet dopants are applied
      into graphene-based electronic devices, which are found to exhibit improved
      device performances. These results demonstrate the potential of GO sheet dopants
      in many graphene-based electronics applications.

PMID- 29457353
TI  - Effect of bristle stiffness of manual toothbrushes on normal and demineralized
      human enamel-An in vitro profilometric study.
AB  - OBJECTIVE: To compare the brushing abrasion carried out by manual toothbrushes
      with different bristle types (hard and soft) on normal and demineralized human
      enamel. MATERIALS AND METHODS: Thirty enamel blocks (N = 30) were prepared and
      were randomly divided into three main groups: A, teeth kept in artificial saliva
      with no brushing (control, n = 2); B, teeth brushed with toothbrushes with hard
      bristles (n = 14); and C, teeth brushed with toothbrushes with soft bristles (n =
      14). Seven teeth belonging to groups B and C were brushed normally, and the
      remaining seven were demineralized before brushing experiments with 6 wt.% citric
      acid (pH = 2.2) for 5 minutes. The brushing experiments were carried out twice a
      day for 2 mins for 7 days inside a toothbrush simulation machine. The changes in
      the surface of enamel (prebrushing and post-brushing) were evaluated using non
      contact profilometry. The results were analysed statistically using Kruskal
      Wallis test and the Wilcoxon signed rank test. RESULTS: For both normal and
      demineralized enamel, toothbrushes with soft bristles caused more abrasion. The
      results revealed significant differences (P = .055) in the surface roughness
      values between the four groups prebrushing. Within each group, the prebrushing
      and post-brushing surface roughness value differences were all statistically
      significant (P < .05). CONCLUSIONS: The results demonstrate that soft bristles
      caused more abrasion as compared with the hard bristles. These results could have
      an impact on the toothbrush recommendations for patients.

PMID- 29457354
TI  - Nitrogen-Enriched Carbon/CNT Composites Based on Schiff-Base Networks: Ultrahigh
      N Content and Enhanced Lithium Storage Properties.
AB  - To improve the electrochemical performance of carbonaceous anodes for lithium ion
      batteries (LIBs), the incorporation of both well-defined heteroatom species and
      the controllable 3D porous networks are urgently required. In this work, a novel
      N-enriched carbon/carbon nanotube composite (NEC/CNT) through a chemically
      induced precursor-controlled pyrolysis approach is developed. Instead of
      conventional N-containing sources or precursors, Schiff-base network (SNW-1)
      enables the desirable combination of a 3D polymer with intrinsic microporosity
      and ultrahigh N-content, which can significantly promote the fast transport of
      both Li+ and electron. Significantly, the strong interaction between carbon
      skeleton and nitrogen atoms enables the retention of ultrahigh N-content up to 21
      wt% in the resultant NEC/CNT, which exhibits a super-high capacity (1050 mAh g-1
      ) for 1000 cycles and excellent rate performance (500 mAh g-1 at a current
      density of 5 A g-1 ) as the anode material for LIBs. The NEC/CNT composite
      affords a new model system as well as a totally different insight for deeply
      understanding the relationship between chemical structures and lithium ion
      storage properties, in which chemistry may play a more important role than
      previously expected.

PMID- 29457355
TI  - Visceral obesity is a significant risk factor for incisional hernia after
      laparoscopic colorectal surgery: A single-center review.
AB  - INTRODUCTION: Although laparoscopic surgery uses relatively small incisions,
      incisional hernia after surgery is not uncommon. However, the incidence of
      incisional hernia and its risk factors are not well known. The purpose of our
      study was to investigate risk factors for incisional hernia after laparoscopic
      colorectal cancer surgery. METHODS: The study group consisted of 212 patients who
      underwent laparoscopic colorectal cancer surgery at Hiroshima Prefectural
      Hospital between November 2008 and October 2013. Diagnosis of incisional hernia
      was performed by postoperative CT. The visceral fat area (VFA) and subcutaneous
      fat area at the level of the umbilicus were calculated using an image analysis
      system. For statistical analysis, Fisher's exact test or Student's t-test were
      used for univariate analysis, and logistic regression analysis was used for
      multivariate analysis. The cut-off value for risk factors was calculated from the
      receiver-operator curve. RESULTS: Incisional hernia was observed in 18 patients
      (8.5%). On univariate analysis, female sex (P = 0.04), older age (P = 0.02),
      subcutaneous fat area (P < 0.01), VFA (P = 0.02), and BMI >25 kg/m2 (P < 0.01)
      were significant risk factors for incisional hernia. The predictive cut-off
      values were as follows: age, 72 years; subcutaneous fat area, 110 cm2 ; VFA, 110
      cm2 ; and albumin concentration, 3.9 g/dL. On multivariate analysis, a VFA >110
      cm2 (P < 0.01) and female sex (P = 0.01) were retained as independent risk
      factors for incisional hernia. CONCLUSION: After laparoscopic colorectal cancer
      surgery, a higher VFA and female sex are independent risk factors for incisional
      hernia.

PMID- 29457356
TI  - Waking up to the importance of sleeping well for cardiovascular health.

PMID- 29457357
TI  - Improving outpatient advance care planning for adults with congenital or
      pediatric heart disease followed in a pediatric heart failure and transplant
      clinic.
AB  - OBJECTIVE: To improve outpatient advanced care planning (ACP) for adults with
      congenital/pediatric heart disease followed in a pediatric heart failure (HF) and
      transplant clinic through quality improvement (QI) methodology. DESIGN: A one
      year QI project was completed. We conducted quarterly chart reviews and
      incorporated feedback from the providers to direct subsequent interventions.
      PATIENTS AND SETTING: Patients >=18 years of age seen in the HF and Transplant
      Clinic for follow-up visit were included in analysis. INTERVENTIONS:
      Interventions focused on five main areas: identifying and training providers to
      have ACP discussions, standardizing the ACP discussion, standardizing ACP and
      advance directive (AD) documentation in the electronic medical record, preparing
      providers to have ACP conversations, and preparing patients to engage in ACP and
      AD completion. OUTCOME MEASURES: The outcome measure was percent of adults seen
      in the HF and Transplant Clinic per month with documented AD (goal 50%). The
      process measure was percent of adults seen in the HF and Transplant Clinic per
      month with a documented ACP discussion (goal 100%). RESULTS: At baseline, no
      patients had a documented ACP discussion or AD. Fifty-eight adults (mean age 20.4
      +/- 2.1 years) were seen from March 2016 to February 2017 for a total of 130
      visits. In the final month of our study, 75% of adult encounters had a documented
      ACP discussion and 42% had a documented AD. CONCLUSIONS: The percentage of
      documented ADs in adults seen in the HF and Transplant Clinic at a quaternary
      children's hospital improved through a QI initiative. Over 50% of patients who
      were engaged in an ACP discussion completed an AD, suggesting this population is
      receptive to ACP and AD completion.

PMID- 29457358
TI  - CRT Survey II: a European Society of Cardiology survey of cardiac
      resynchronisation therapy in 11 088 patients-who is doing what to whom and how?
AB  - BACKGROUND: Cardiac resynchronisation therapy (CRT) reduces morbidity and
      mortality in appropriately selected patients with heart failure and is strongly
      recommended for such patients by guidelines. A European Society of Cardiology
      (ESC) CRT survey conducted in 2008-2009 showed considerable variation in
      guideline adherence and large individual, national and regional differences in
      patient selection, implantation practice and follow-up. Accordingly, two ESC
      associations, the European Heart Rhythm Association and the Heart Failure
      Association, designed a second prospective survey to describe contemporary
      clinical practice regarding CRT. METHODS AND RESULTS: A survey of the clinical
      practice of CRT-P and CRT-D implantation was conducted from October 2015 to
      December 2016 in 42 ESC member countries. Implanting centres provided information
      about their hospital and CRT service and were asked to complete a web-based case
      report form collecting information on patient characteristics, investigations,
      implantation procedures and complications during the index hospitalisation. The
      11 088 patients enrolled represented 11% of the total number of expected
      implantations in participating countries during the survey period; 32% of
      patients were aged >=75 years, 28% of procedures were upgrades from a permanent
      pacemaker or implantable cardioverter-defibrillator and 30% were CRT-P rather
      than CRT-D. Most patients (88%) had a QRS duration >=130 ms, 73% had left bundle
      branch block and 26% were in atrial fibrillation at the time of implantation.
      Large geographical variations in clinical practice were observed. CONCLUSION: CRT
      Survey II provides a valuable source of information on contemporary clinical
      practice with respect to CRT implantation in a large sample of ESC member states.
      The survey permits assessment of guideline adherence and demonstrates variations
      in patient selection, management, implantation procedure and follow-up strategy.

PMID- 29457359
TI  - Discrimination between zeranol and zearalenone exposure using hair analysis.
      Application to an adverse analytical finding case.

PMID- 29457360
TI  - Neglected areas on thorax computed tomography evaluation in patients with chronic
      obstructive pulmonary disease: Paravertebral muscles and para-aortic adipose
      tissue.
AB  - INTRODUCTION: This study, investigated the para-aortic adipose tissue cross
      sectional area, a novel predictor of cardiovascular diseases and degenerative
      changes in the paravertebral muscles, in patients with chronic obstructive
      pulmonary disease (COPD). METHOD: One hundred cases diagnosed as COPD and 50
      healthy individuals with similar demographic characteristics were evaluated. Para
      aortic adipose tissue cross-sectional area (mm2 ), subcutaneous adipose tissue
      thickness (mm), paravertebral muscle area (mm2 ) and fat deposition in muscle
      tissue were assessed radiologically. RESULTS: Paravertebral muscle mass was lower
      in the patient group compared to the healthy individuals (471.41 +/- 157.71 mm2
      and 561.58 + 151.03 mm2 , respectively; P = 0.001). Paravertebral muscle
      attenuation values were also lower in the patient group, and the grade of
      deposition increased (P = 0.012 and P = 0.045, respectively). Although
      subcutaneous adipose tissue thicknesses were similar in the patient and control
      groups, para-aortic adipose tissue cross-sectional area was higher in the
      patients with COPD than in the control group (439.34 +/- 267.17 mm2 and 333.82 +/
      165.23 mm2 , respectively, P = 0.012). The correlation between subcutaneous
      adipose tissue and para-aortic adipose tissue observed in the healthy group was
      not present in the subjects with COPD. CONCLUSION: Chronic obstructive pulmonary
      disease causes morphological changes in paravertebral muscles and para-aortic
      adipose tissue. Degenerative changes in the paravertebral muscles occur secondary
      to systemic inflammation, comorbidity and drugs used in COPD. Factors such as
      insulin resistance and steroid use result in an increase in para-aortic adipose
      tissue mass.

PMID- 29457361
TI  - Cognitive function and unsafe driving acts during an on-road test among community
      dwelling older adults with cognitive impairments.
AB  - AIM: To examine the relationship between cognitive function and unsafe driving
      acts among community-dwelling older adults with cognitive impairments. METHODS:
      Participants (n = 160) were older residents of Obu, Japan, aged >=65 years with
      cognitive impairments. They regularly drove and were assessed for the number of
      unsafe driving acts without adequate verification during an on-road test. We also
      evaluated cognitive function (attention, executive function and processing
      speed). Other examined variables included demographics, driving characteristics
      and visual condition. RESULTS: Participants were classified into two groups
      according to the number of unsafe driving acts as follows: high group (>=4 unsafe
      driving acts) and low group (<=3 unsafe driving acts). The high group
      participants were older in age (P < 0.001) and obtained a lower score on the
      symbol digit substitution task (P = 0.002) than the low group. The number of
      unsafe driving acts showed modest significant positive correlations with age (r =
      0.396, P < 0.001). The symbol digit substitution task score was significantly
      associated with the number of unsafe driving acts (beta = -0.196, P < 0.05) after
      adjusting for age group. CONCLUSIONS: Processing speed was associated with unsafe
      driving acts that became worse with increasing age. Future study will be required
      to longitudinally examine the influence of processing speed on traffic accidents
      for those with cognitive impairments. Geriatr Gerontol Int 2018; 18: 847-852.

PMID- 29457363
TI  - Conventional laparoscopic appendectomy versus double-incision, three-port
      laparoscopic appendectomy: A 1-year randomized controlled trial.
AB  - INTRODUCTION: Management of appendicitis has evolved dramatically in the last 120
      years, from McBurney's large incision to minimally invasive laparoscopic
      appendectomy to hardly noticeable incisions with SILS. As a bridge between
      conventional laparoscopic surgery and SILS, double-incision laparoscopic surgery
      further minimizes the invasiveness of laparoscopic surgery by reducing the number
      of incisions. This study aimed to establish the efficacy of double-incision,
      three-port laparoscopic appendectomy (DILA) as an alternative to conventional
      three-port laparoscopic appendectomy. METHODS: A total of 60 patients were
      divided randomly into two groups: the conventional laparoscopic appendectomy
      (CLA) group and the DILA appendectomy group. Demographics, diagnostic history,
      additional intraoperative findings, and duration of operation were recorded.
      Postoperative pain after 6 h and 24 h and cosmetic outcome after the surgery were
      also evaluated. Statistical analysis was done using Fisher's exact test, chi2
      test, and Student's t-test. RESULTS: No significant difference was observed in
      demographic and clinical characteristics in either group (P > 0.05). No
      significant difference in mean postoperative pain was observed between the two
      groups at 6 h (P = 0.62) or 24 h (P = 0.484). However, patients in the DILA group
      were more satisfied with their cosmetic outcomes than those in the CLA group (P =
      0.04). The mean operative time was 26.4 min in the CLA group and 27.6 min in the
      DILA group (P = 0.62). CONCLUSION: DILA can be performed with operative outcomes
      that are equivalent to CLA but with superior cosmetic outcomes.

PMID- 29457364
TI  - Transmission electron microscopy analysis of the origin and incidence of sperm
      intranuclear cytoplasmic retention in fertile and teratozoospermia men.
AB  - The human sperm nucleus contains cytoplasm. However, the origin and incidence of
      human sperm intranuclear cytoplasmic retention (INCR) remain unknown. The
      objectives of this study were to observe the morphological origin of INCR within
      the seminiferous epithelium and investigate the incidence of INCR in fertile and
      teratozoospermia men using transmission electron microscopy (TEM). By TEM, INCR
      initially appeared in elongating round spermatid nuclei and varied in size,
      number, shape, content, location and distribution within sperm nuclei. The
      teratozoospermia group (n = 16) demonstrated a higher incidence of INCR than did
      the fertile group (n = 16) (17.6 +/- 5.2% vs. 9.7 +/- 3.4%; p = 0.000). In the
      fertile group, no correlations were found between the incidence of INCR and
      abnormal sperm morphology, nuclear vacuole, acrosome integrity, motility or
      concentration (p > 0.05). However, the incidence of INCR exhibited a positive
      relationship with sperm abnormal morphology in the teratozoospermia group (r =
      0.616, p = 0.011). These results demonstrate that INCR occurs in the early
      process of spermatogenesis and is an alteration found in the nucleus. Spermatozoa
      from teratozoospermia men contained more INCRs than those from fertile males.
      More attention should be paid to the possibility of spermatozoa containing INCR
      when using spermatozoa with abnormal head morphology for clinical or diagnostic
      purposes.

PMID- 29457362
TI  - A multinational observational investigation of illness perceptions and quality of
      life among patients with a Fontan circulation.
AB  - OBJECTIVE: First, to compare QOL and illness perceptions between patients with a
      Fontan circulation and patients with anatomically simple defects (ie, atrial
      septal defects [ASD] or ventricular septal defects [VSD]). Second, to explore
      illness perceptions as a mediator of the association between congenital heart
      disease (CHD) diagnosis and QOL. DESIGN: Cross-sectional observational study.
      SETTING: Twenty-four cardiology centers from 15 countries across five continents.
      PATIENTS: Four hundred thirty-five adult patients with congenital heart disease
      (177 Fontan and 258 ASD/VSD) ages 18-83 years. OUTCOME MEASURES: QOL and illness
      perceptions were assessed by the Satisfaction With Life Scale and the Brief
      Illness Perceptions Questionnaire, respectively. RESULTS: Patients with a Fontan
      circulation reported lower QOL (Wald Z = -3.59, p = <.001) and more negative
      perceptions of their CHD (Wald Z = -7.66, p < .001) compared with patients with
      ASD/VSD. After controlling for demographics, anxiety, depressive symptoms, and
      New York Heart Association functional class, path analyses revealed a significant
      mediation model, alphabeta = 0.15, p = .002, 95% CI = 0.06-0.25, such that CHD
      diagnosis was indirectly related to QOL through illness perceptions. CONCLUSIONS:
      The Fontan sample's more negative perceptions of CHD were likely a reflection of
      life with a more complex defect. Illness perceptions appear to account for unique
      differences in QOL between groups of varying CHD complexity. Psychosocial
      screening and interventions may be important treatment components for patients
      with CHD, particularly those with Fontan circulations.

PMID- 29457365
TI  - Male infertility is associated with altered treatment course of men with cancer.
AB  - This study aims to evaluate whether cancer treatments differ in infertile men
      compared to men who have undergone vasectomy and age-matched controls. We
      analyzed subjects from the Truven Health MarketScan Claims database from 2001 to
      2009. Infertile men were identified through diagnosis and treatment codes.
      Comparison groups included vasectomized men and an age-matched cohort who were
      not infertile and had not undergone vasectomy. We considered cancer types
      previously associated with infertility that were diagnosed after the diagnosis of
      infertility. The treatment regimens were determined based on the presence of
      claims with CPT codes for chemotherapy (CTX), radiation (RTX) or surgical
      treatment (ST) for each entity in all study groups. Cases with multimodal
      treatments were also identified. As a result, CTX was similarly distributed among
      the infertile, vasectomized, and control groups. In contrast, RTX treatment
      length was shorter in infertile men. The frequency of multimodal treatment (i.e.,
      radiation and chemotherapy) was twofold lower in men with infertility compared to
      other men. By focusing on treatment patterns for each cancer type among these
      groups, the duration of RTX and CTX was shorter in infertile men diagnosed with
      NHL compared to controls. We conclude that Infertile men diagnosed with cancer
      and specific cancer types experience different treatment courses, with shorter
      RTX and less combined RTX/CTX compared to fertile and vasectomized men. These
      differences could reflect differences in stage at presentation, biological
      behavior, or treatment responses in infertile men.

PMID- 29457366
TI  - Is the laparoscopic approach appropriate for pediatric subhepatic appendicitis?
AB  - INTRODUCTION: Subhepatic appendicitis in children is an unusual condition that
      can be challenging for the pediatric surgeons to treat. The aim of our study was
      to compare the outcomes of laparoscopic appendectomies based on the position of
      the appendix. METHODS: The data of 1736 patients who had undergone laparoscopic
      appendectomy in our tertiary center were retrospectively reviewed. We compared
      two groups: subhepatic location (n = 56) and non-subhepatic location (n = 1680).
      A P-value of less than 0.05 was considered statistically significant. RESULTS:
      There was no statistically significant difference between the demographic
      variables of the groups. More than half of the subhepatic appendicitises were
      gangrenous (44.6%) or perforated (16.1%), whereas most of the non-subhepatic
      appendicitises were phlegmonous (56.9%). Extracorporeal ligation of the appendix
      was the preferred technique in both the subhepatic and non-subhepatic groups
      (69.6% and 89.8%, respectively). The subhepatic group had a statistically
      significant higher incidence of technical difficulties (1.6%) and abdominal drain
      (18.6%) than the non-subhepatic group, as well as a longer operative time and
      hospital stay. However, intraoperative and postoperative complications were
      similar in both groups. CONCLUSION: Laparoscopic subhepatic appendectomy is safe
      and does not lead to increased complications. However, the technique is made
      difficult by the fact that the appendix is an atypical location, and the rate of
      complicated appendicitis is higher.

PMID- 29457367
TI  - Sperm morphological normality under high magnification is correlated to male
      infertility and predicts embryo development.
AB  - Human sperm morphology has been described as an essential parameter for the
      diagnosis of male infertility and a prognostic indicator of natural or assisted
      pregnancies. Nevertheless, standard morphological assessment remains a subjective
      analysis and its impact on intracytoplasmic sperm injection (ICSI) is also of
      limited value. The objective of this prospective cohort study was to investigate
      whether motile sperm organelle morphology examination (MSOME) can improve semen
      analysis by better defining male infertility and providing a better prognosis for
      ICSI up to a year later. Data were obtained from 483 patients undergoing
      conventional semen analysis from June 2015 to June 2017 in a private university
      affiliated in vitro fertilization (IVF) center. The correlation of MSOME with
      seminal parameters was evaluated. One hundred and thirty patients underwent ICSI
      up to a year later, and the correlation between MSOME and ICSI outcomes was
      established. Except for volume, all seminal parameters were positively correlated
      with MSOME I+II. MSOME was also distinct between World Health Organization (WHO)
      classification groups, with normozoospermic and oligoasthenoteratozoospermic
      presenting the higher and the lower proportion of MSOME I+II, respectively. MSOME
      I+II was prognostic for fertilization rate, high-quality cleavage-stage embryos
      rate, and blastocyst rate. The normality cutoff value based on blastocyst rate
      was MSOME I+II>= 5.5%. MSOME could be a useful tool for the diagnosis of
      infertility severity as it is correlated with sperm morphology, motility, and
      concentration. Men who had higher MSOME I+II had better ICSI outcomes. The future
      use of MSOME as a routine method for semen analysis may be a reliable form of
      assessing male infertility.

PMID- 29457369
TI  - Internet Searches for Affect-Related Terms: An Indicator of Subjective Well-Being
      and Predictor of Health Outcomes across US States and Metro Areas.
AB  - BACKGROUND: The present study explored the potential for internet search data to
      serve as indicators of subjective well-being (SWB) and predictors of health at
      the state and metro area levels. We propose that searches for positive and
      negative affect-related terms represent information-seeking behavior of
      individuals who are experiencing emotions and seeking information about them.
      METHOD: Data on the frequency of Google searches for 15 affect terms were
      collected from Google's Trends website (trends.google.com). These were paired
      with data on health, self-reported emotions, psychological well-being,
      personality, and Twitter postings at the state and metro area levels. RESULTS:
      Several internet search scores correlated with indicators of cardiovascular
      health and depression. Some search term scores also correlated strongly with self
      reported emotions, well-being metrics, neuroticism, per capita income, and
      Twitter postings at the state or metro area level. Multiple regression analyses
      suggest that affect searches predict depression rates at the metro area level
      beyond the effects of income and other well-being measures. CONCLUSION: The
      results highlight the promise and challenges of using internet search data at the
      aggregate level for physical and mental health assessment and surveillance.

PMID- 29457368
TI  - Emergence of two novel sublineages Ind2001BD1 and Ind2001BD2 of foot-and-mouth
      disease virus serotype O in Bangladesh.
AB  - Foot-and-mouth disease (FMD) is endemic in Bangladesh, and the implementation of
      a control programme for this disease is at an early stage, according to the FAO-
      and OIE-proposed Progressive Control Pathway for FMD (PCP-FMD) Roadmap. To
      develop an effective control programme, understanding of foot-and-mouth disease
      virus (FMDV) serotypes, even subtypes within the serotypes is essential. The
      present investigation aims at viral VP1 coding region sequence-based analysis of
      FMD samples collected from 34 FMD outbreaks during 2012-2016 in Bangladesh. Foot
      and-mouth disease virus (FMDV) serotype O was responsible for 82% of the
      outbreaks in Bangladesh, showing its dominance over serotype A and Asia1. The VP1
      phylogeny revealed the emergence of two novel sublineages of serotype O, named as
      Ind2001BD1 and Ind2001BD2, within the Ind2001 lineage along with the circulation
      of Ind2001d sublineage in Bangladesh, which was further supported by the
      multidimensional scaling with distinct clusters for each sublineage. The novel
      sublineages had evident genetic variability with other established sublineages
      within Ind2001 lineage. Ten mutations with three or more amino acid variations
      were detected within B-C loop, G-H loop and C-terminal region of the VP1 protein
      of FMDV serotype O viruses isolated exclusively from Bangladesh. Furthermore, two
      amino acid substitutions at positions 197 and 198 within the VP1 C-terminal
      region are unique to the novel sublineages. The existence of widespread genetic
      variations among circulatory FMDV serotype O viruses makes the FMD control
      programme complex in Bangladesh. Adequate epidemiological data, disease
      reporting, animal movement control, appropriate vaccination and above all
      stringent policies of the government are necessary to combat FMD in Bangladesh.

PMID- 29457370
TI  - Avian metapneumovirus subtype C in Wild Waterfowl in Ontario, Canada.
AB  - Avian metapneumovirus (aMPV) is an emerging poultry pathogen that has a
      significant economic impact on poultry production worldwide. The geographic range
      of the virus continues to expand, and wild birds have been implicated as
      reservoirs of aMPV that have the potential to spread the virus over long
      distances. Our objective was to determine the apparent prevalence of aMPV subtype
      C in wild waterfowl in Ontario, Canada. Wild waterfowl were captured in August
      and September, 2016 as part of routine migratory waterfowl population monitoring
      by the Ontario Ministry of Natural Resources and Forestry. Oropharyngeal and
      cloacal swabs were collected from each bird and placed together for aMPV testing
      using real-time RT-PCR. A total of 374 live wild birds from 23 lakes were sampled
      and tested for aMPV. Among all ducks tested, 84 (22%) were positive for aMPV. The
      proportion of samples that tested positive ranged from 0% in ring-necked ducks
      (Aythya collaris) and green-winged teal (Anas carolinensis) to 44% (8 of 18) in
      American black ducks (A. rubripes). Waterfowl positive for aMPV were found at 14
      of 23 lakes in the study area and the percent positive at these 14 lakes ranged
      between 5% and 84%. Although subtype C aMPV has been detected in a variety of
      wild birds in North America, this is the first report of aMPV in wild ducks in
      Ontario, Canada. The high apparent prevalence, particularly in mallards and
      American black ducks (37 and 44%, respectively), suggests that these species may
      be important reservoirs of aMPV. Given the potential impact of aMPV on domestic
      poultry and the potential role of wild birds as reservoirs of the virus, further
      investigation of the geographic distribution, risk factors associated with aMPV
      carriage in wild waterfowl and potential role of other birds in the epidemiology
      of aMPV in Canada is warranted.

PMID- 29457371
TI  - Validation of a blood marker for plasma volume in endurance athletes during a
      live-high train-low altitude training camp.
AB  - Altitude is a confounding factor within the Athlete Biological Passport (ABP)
      due, in part, to the plasma volume (PV) response to hypoxia. Here, a newly
      developed PV blood test is applied to assess the possible efficacy of reducing
      the influence of PV on the volumetric ABP markers; haemoglobin concentration
      ([Hb]) and the OFF-score. Endurance athletes (n=34) completed a 21-night
      simulated live-high train-low (LHTL) protocol (14 h.d-1 at 3000 m). Bloods were
      collected twice pre-altitude; at days 3, 8, and 15 at altitude; and 1, 7, 21, and
      42 days post-altitude. A full blood count was performed on the whole blood
      sample. Serum was analysed for transferrin, albumin, calcium, creatinine, total
      protein, and low-density lipoprotein. The PV blood test (consisting of the serum
      markers, [Hb] and platelets) was applied to the ABP adaptive model and new
      reference predictions were calculated for [Hb] and the OFF-score, thereby
      reducing the PV variance component. The PV correction refined the ABP reference
      predictions. The number of atypical passport findings (ATPFs) for [Hb] was
      reduced from 7 of 5 subjects to 6 of 3 subjects. The OFF-score ATPFs increased
      with the PV correction (from 9 to 13, 99% specificity); most likely the result of
      more specific reference limit predictions combined with the altitude-induced
      increase in red cell production. Importantly, all abnormal biomarker values were
      identified by a low confidence value. Although the multifaceted, individual
      physiological response to altitude confounded some results, the PV model appears
      capable of reducing the impact of PV fluctuations on [Hb].

PMID- 29457373
TI  - Visible Light-Driven Water Oxidation on an In Situ N2 -Intercalated WO3 Nanorod
      Photoanode Synthesized by a Dual-Functional Structure-Directing Agent.
AB  - With a view to developing a photoanode for visible light-driven water oxidation
      in solar water splitting cells, pure-monoclinic WO3 nanorod crystals with N2
      intercalated into the lattice were synthesized by using hydrazine with a dual
      functional role-as an N atom source for the in situ N2 intercalation and as a
      structure-directing agent for the nanorod architecture-to gain higher incident
      photon-to-current conversion efficiency at 420 nm than with most previously
      reported WO3 electrodes.

PMID- 29457372
TI  - Clinical Characteristics and Factors Associated With Disability and Impaired
      Quality of Life in Children With Juvenile Systemic Sclerosis: Results From the
      Childhood Arthritis and Rheumatology Research Alliance Legacy Registry.
AB  - OBJECTIVE: To investigate clinical manifestations of juvenile systemic sclerosis
      (SSc; scleroderma), including disease characteristics and patient quality of
      life, using the multinational Childhood Arthritis and Rheumatology Research
      Alliance (CARRA) Legacy Registry. METHODS: Patients with juvenile SSc were
      prospectively enrolled between 2010 and 2013. The diagnosis of juvenile SSc was
      determined by the enrolling pediatric rheumatologist, with the requirement for
      disease onset prior to age 18 years. Collected data included demographics,
      disease characteristics, medication exposure, and quality of life metrics.
      RESULTS: In total, 64 patients with juvenile SSc were enrolled a median of 3.6
      years after disease onset, which occurred at a median age of 10.3 years. The most
      common organ manifestations were dermatologic and vascular, followed by
      musculoskeletal, gastrointestinal, and pulmonary; in 38% of patients, >=4 organ
      systems were affected. Patients with juvenile SSc had significantly more
      disability at enrollment compared with CARRA Legacy Registry patients with
      juvenile idiopathic arthritis, dermatomyositis, or systemic lupus erythematosus.
      Although physician-reported measures correlated most closely with arthritis,
      dermatologic manifestations, and pulmonary manifestations, poor patient-reported
      measures were associated with gastrointestinal involvement. During >50 person
      years of follow-up, most organ manifestations remained stable, and no mortality
      or development of new solid organ involvement after enrollment was reported.
      CONCLUSION: In the first multicenter prospective cohort of patients with juvenile
      SSc in North America, the disease burden was high: multiorgan manifestations were
      common, and functional disability was greater than that observed in patients with
      other childhood-onset rheumatic diseases. Gastrointestinal involvement had the
      greatest impact on quality of life.

PMID- 29457374
TI  - Impaired Proteasomal Function in Human Osteoarthritic Chondrocytes Can Contribute
      to Decreased Levels of SOX9 and Aggrecan.
AB  - OBJECTIVE: Osteoarthritis (OA) chondrocytes exhibit impairment of autophagy, one
      arm of the proteostasis network that coordinates proteome and organelle quality
      control and degradation. Deficient proteostasis impacts differentiation and
      viability, and inflammatory processes in aging and disease. The present study was
      undertaken to assess ubiquitin proteasome system proteasomal function in OA
      chondrocytes. METHODS: We evaluated human knee cartilage by immunohistochemistry,
      and assessed proteasomal function, levels of proteasomal core subunits and
      chaperones, and autophagy in cultured chondrocytes. Assays included Western
      blotting, quantitative reverse transcription-polymerase chain reaction,
      proteasomal protease activity assessment, and cell immunofluorescence analysis.
      RESULTS: Human knee OA cartilage exhibited polyubiquitin accumulation, with
      increased ubiquitin K48-linked polyubiquitinated proteins in situ, suggesting
      proteasomal impairment. Cultured OA chondrocytes demonstrated accumulation of K48
      polyubiquitinated proteins, significantly reduced 20S proteasome core protease
      activity, and decreased levels of phosphorylated FOXO4 and proteasome 26S
      subunit, non-ATPase 11 (PSMD11), a FOXO4-inducible promoter of proteasomal
      activation. Levels of proteasome subunit beta type 3 (PSMB3), PSMB5, PSMB6, and
      proteasome assembly chaperone 1 were not decreased in OA chondrocytes. In normal
      chondrocytes, PSMD11 small interfering RNA knockdown stimulated certain autophagy
      machinery elements, increased extracellular nitric oxide (NO) levels, and reduced
      chondrocytic master transcription factor SOX9 protein and messenger RNA (mRNA)
      and aggrecan (AGC1) mRNA. PSMD11 gain-of- function by transfection increased
      proteasomal function, increased levels of SOX9-induced AGC1 mRNA, stimulated
      elements of the autophagic machinery, and inhibited extracellular levels of
      interleukin-1-induced NO and matrix metalloproteinase 13 in OA chondrocytes.
      CONCLUSION: Deficient PSMD11, associated with reduced phosphorylated FOXO4,
      promotes impaired proteasomal function in OA chondrocytes, dysregulation of
      chondrocytic homeostasis, and decreased levels of SOX9 mRNA, SOX9 protein, and
      AGC1 mRNA. Chondrocyte proteasomal impairment may be a therapeutic target for OA.

PMID- 29457375
TI  - Evidence of Alternative Modes of B Cell Activation Involving Acquired Fab Regions
      of N-Glycosylation in Antibody-Secreting Cells Infiltrating the Labial Salivary
      Glands of Patients With Sjogren's Syndrome.
AB  - OBJECTIVE: To better understand the role of B cells, the potential mechanisms
      responsible for their aberrant activation, and the production of autoantibodies
      in the pathogenesis of Sjogren's syndrome (SS), this study explored patterns of
      selection pressure and sites of N-glycosylation acquired by somatic mutation (acN
      glyc) in the IgG variable (V) regions of antibody-secreting cells (ASCs) isolated
      from the minor salivary glands of patients with SS and non-SS control patients
      with sicca symptoms. METHODS: A novel method to produce and characterize
      recombinant monoclonal antibodies (mAb) from single cell-sorted ASC infiltrates
      was applied to concurrently probe expressed genes (all heavy- and light-chain
      isotypes as well as any other gene of interest not related to immunoglobulin) in
      the labial salivary glands of patients with SS and non-SS controls. V regions
      were amplified by reverse transcription-polymerase chain reaction, sequenced, and
      analyzed for the incidence of N-glycosylation and selection pressure. For
      specificity testing, the amplified regions were expressed as either the native
      mAb or mutant mAb lacking the acN-glyc motif. Protein modeling was used to
      demonstrate how even an acN-glyc site outside of the complementarity-determining
      region could participate in, or inhibit, antigen binding. RESULTS: V-region
      sequence analyses revealed clonal expansions and evidence of secondary light
      chain editing and allelic inclusion, of which neither of the latter two have
      previously been reported in patients with SS. Increased frequencies of acN-glyc
      were found in the sequences from patients with SS, and these acN-glyc regions
      were associated with an increased number of replacement mutations and lowered
      selection pressure. A clonal set of polyreactive mAb with differential framework
      region 1 acN-glyc motifs was also identified, and removal of the acN-glyc could
      nearly abolish binding to autoantigens. CONCLUSION: These findings support the
      notion of an alternative mechanism for the selection and proliferation of some
      autoreactive B cells, involving V-region N-glycosylation, in patients with SS.

PMID- 29457377
TI  - Pseudohalide-Induced 2D (CH3 NH3 )2 PbI2 (SCN)2 Perovskite for Ternary Resistive
      Memory with High Performance.
AB  - Recently, organic-inorganic hybrid perovskites (OIHP) are studied in memory
      devices, but ternary resistive memory with three states based on OIHP is not
      achieved yet. In this work, ternary resistive memory based on hybrid perovskite
      is achieved with a high device yield (75%), much higher than most organic ternary
      resistive memories. The pseudohalide-induced 2D (CH3 NH3 )2 PbI2 (SCN)2
      perovskite thin film is prepared by using a one-step solution method and
      fabricated into Al/perovskite film/indium-tin oxide (glass substrate as well as
      flexible polyethylene terephthalate substrate) random resistive access memory
      (RRAM) devices. The three states have a conductivity ratio of 1:103 :107 , long
      retention over 10 000 s, and good endurance properties. The electrode area
      variation, impedance test, and current-voltage plotting show that the two
      resistance switches are attributable to the charge trap filling due to the effect
      of unscreened defect in 2D nanosheets and the formation of conductive filaments,
      respectively. This work paves way for stable perovskite multilevel RRAMs in
      ambient atmosphere.

PMID- 29457378
TI  - The use of antihypertensive fixed combinations in clinical practice needs a
      reappraisal.

PMID- 29457376
TI  - Delivery of Allogeneic Adipose Stem Cells in Polyethylene Glycol-Fibrin Hydrogels
      as an Adjunct to Meshed Autografts After Sharp Debridement of Deep Partial
      Thickness Burns.
AB  - Harvesting of autografts results in donor site morbidities and is limited in
      scenarios such as large total body surface area burns. In these instances,
      coverage is increased by meshing grafts at the expense of delayed biologic
      closure. Moreover, graft meshing increases the likelihood of contraction and
      hypertrophic scarring, limits range of motion, and worsens cosmesis. Many tissue
      engineering technologies have touted the promise of adipose-derived stem cells
      (ASCs) for burn wounds. The primary objective of the current study was to
      determine feasibility and efficacy of in situ ASC delivery via PEGylated fibrin
      (FPEG) hydrogels as adjuncts to meshed split thickness skin grafts in a porcine
      model. Deep partial thickness burns were created on the dorsum of anesthetized
      Yorkshire pigs, and subsequently debrided on post-burn day 4. After debridement,
      wounds were treated with: split thickness skin grafts (STSG); meshed STSG
      (mSTSG); and mSTSG + FPEG with increasing doses of ASCs. We show that FPEG
      hydrogels can be delivered in situ to prevent the contraction seen after meshing
      of STSG. Moreover, ASCs delivered in FPEG dose-dependently increase blood vessel
      size which significantly correlates with CD31 protein levels. The current study
      reports a dual-action adjunct therapy to autografting administered in situ,
      wherein FPEG acts as both scaffolding to prevent contraction, and as a delivery
      vehicle for ASCs to accelerate angiogenesis. This strategy may be used to
      incorporate other biologics for generating tissue engineered products aimed at
      improving wound healing and minimizing donor sites or scarring. Stem Cells
      Translational Medicine 2018;7:360-372.

PMID- 29457379
TI  - Levels of Cytokines and MicroRNAs in Individuals With Asymptomatic Hyperuricemia
      and Ultrasonographic Findings of Gout: A Bench-to-Bedside Approach.
AB  - OBJECTIVE: To assess potential associations among serum cytokines and microRNA
      (miR) levels with ultrasound (US) findings suggestive of urate deposits in
      chronic asymptomatic hyperuricemia and gout. METHODS: All participants underwent
      musculoskeletal US and measurements of serum interleukin-1beta (IL-1beta), IL-2,
      IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, interferon-gamma, tumor necrosis
      factor, monocyte chemoattractant protein 1, and epithelial neutrophil-activating
      peptide 78, as well as miR-146a, miR-155, and miR-223 levels. RESULTS: Thirty
      individuals with asymptomatic hyperuricemia, 31 normouricemic controls, and 30
      patients with gout were included. The frequency of synovitis and double contour
      sign using US was similar between asymptomatic hyperuricemia (67% and 27%,
      respectively) and patients with gout (77% and 27%, respectively), and each had a
      higher frequency than controls (45% and 0%, respectively). Serum IL-6 and IL-8
      levels were similar between patients with asymptomatic hyperuricemia (mean +/- SD
      69.7 +/- 73.4 and 18.5 +/- 25.6 pg/ml, respectively) and gout (mean +/- SD 75.8
      +/- 47.6 and 24.4 +/- 31.7 pg/ml, respectively), and higher than controls (mean
      +/- SD 28.2 +/- 17.6 and 7.4 +/- 6.0 pg/ml, respectively). A similar distribution
      was observed for miR-155 levels in asymptomatic hyperuricemia, patients with
      gout, and controls (mean +/- SD 0.22 +/- 0.18, 0.20 +/- 0.14, and 0.08 +/- 0.04,
      respectively). Associations between morphostructural abnormalities suggestive of
      urate deposits (regardless of clinical diagnosis) and serum markers were
      assessed. Subjects with urate deposits had higher IL-6 (257.2 versus 47.0 pg/ml;
      P = 0.005), IL-8 (73.2 versus 12.0 pg/ml; P = 0.026), and miR-155 (0.21 versus
      0.16; P = 0.015) levels than those without deposition findings. CONCLUSION: In
      individuals with chronic asymptomatic hyperuricemia, the presence of synovitis
      and double contour sign by US may represent a subclinical manifestation of
      monosodium urate crystal nucleation, capable of triggering inflammatory pathways
      (IL-6 and IL-8) and mechanisms of intercellular communication (miR-155), similar
      to what is observed in patients with gout.

PMID- 29457380
TI  - Two-Step Assembly of Thermoresponsive Gold Nanorods Coated with a Single Kind of
      Ligand.
AB  - Gold nanorods (GNRs) coated with a single kind of ligand show thermoreponsive two
      step assembly to provide a hierarchical structure. The GNRs (33 nm in length * 14
      nm in diameter) coated with a hexa(ethylene glycol) (HEG) derivative form side-by
      side assemblies at 30  degrees C (TA1 ) as a steady state through dehydration. By
      further heating to over 40  degrees C (TA2 ), larger assemblies, which are
      composed of the side-by-side assembled units, are formed as hierarchical
      structures. The dehydration temperature of the HEG derivative varies depending on
      the free volume of the HEG unit, which corresponds to the curvature of the GNRs.
      Upon heating, dehydration first occurs from the ligands on the side portions with
      a lower curvature, and then from the ligands on the edge portions with a higher
      curvature. The different sized GNRs (33 * 8 and 54 * 15 nm) also show two-step
      assembly. Both the TA1 and TA2 are dependent on the diameter of the GNRs, but
      independent of their length. This result supports that the dehydration is
      dependent on the free volume, which corresponds to the curvature. Anisotropic
      assembly focusing on differences in curvature provides new guidelines for the
      fabrication of hierarchical structures.

PMID- 29457381
TI  - A Multicenter Study of the Validity and Reliability of Responses to Hand Cold
      Challenge as Measured by Laser Speckle Contrast Imaging and Thermography: Outcome
      Measures for Systemic Sclerosis-Related Raynaud's Phenomenon.
AB  - OBJECTIVE: Reliable and objective outcome measures to facilitate clinical trials
      of novel treatments for systemic sclerosis (SSc)-related Raynaud's phenomenon
      (RP) are badly needed. Laser speckle contrast imaging (LSCI) and thermography are
      noninvasive measures of perfusion that have shown excellent potential. This
      multicenter study was undertaken to determine the reliability and validity of a
      hand cold challenge protocol using LSCI, standard thermography, and low-cost cell
      phone/mobile phone thermography (henceforth referred to as mobile thermography)
      in patients with SSc-related RP. METHODS: Patients with RP secondary to SSc were
      recruited from 6 UK tertiary care centers. The patients underwent cold challenge
      on 2 consecutive days. Changes in cutaneous blood flow/skin temperature at each
      visit were imaged simultaneously using LSCI, standard thermography, and mobile
      thermography. Measurements included area under the curve (AUC) for
      reperfusion/rewarming and maximum blood flow rate/skin temperature after
      rewarming (MAX). Test-retest reliability was assessed using intraclass
      correlation coefficients (ICCs). Estimated latent correlations (estimated from
      multilevel models, taking values between -1 and 1; denoted as rho values) were
      used to assess the convergent validity of LSCI and thermography. RESULTS: In
      total, 159 patients (77% with limited cutaneous SSc) were recruited (84% female,
      median age 63.3 years). LSCI and standard thermography both had substantial
      reliability, with ICCs for the reperfusion/rewarming AUC of 0.67 (95% confidence
      interval [95% CI] 0.54, 0.76) and 0.68 (95% CI 0.58, 0.80), respectively, and
      ICCs for the MAX of 0.64 (95% CI 0.52, 0.75) and 0.72 (95% CI 0.64, 0.81),
      respectively. Very high latent correlations were present for the AUCs of LSCI and
      thermography (rho = 0.94; 95% CI 0.87, 1.00) and for the AUCs of standard and
      mobile thermography (rho = 0.98; 95% CI 0.94, 1.00). CONCLUSION: This is the
      first multicenter study to examine the reliability and validity of cold challenge
      using LSCI and thermography in patients with SSc-related RP. LSCI and
      thermography both demonstrated good potential as outcome measures. LSCI, standard
      thermography, and mobile thermography had very high convergent validity.

PMID- 29457383
TI  - Continuing Professional Development.

PMID- 29457382
TI  - An International Multispecialty Validation Study of the IgG4-Related Disease
      Responder Index.
AB  - OBJECTIVE: IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in
      nearly any organ, leading to organ dysfunction and failure. The IgG4-RD Responder
      Index (RI) was developed to help investigators assess the efficacy of treatment
      in a structured manner. The aim of this study was to validate the RI in a
      multinational investigation. METHODS: The RI guides investigators through
      assessments of disease activity and damage in 25 domains, incorporating higher
      weights for disease manifestations that require urgent treatment or that worsen
      despite treatment. After a training exercise, investigators reviewed 12 written
      IgG4-RD vignettes based on real patients. Investigators calculated both an RI
      score as well as a physician's global assessment (PhGA) score for each vignette.
      In a longitudinal assessment, 3 investigators used the RI in 15 patients with
      newly active disease who were followed up over serial visits after treatment. We
      assessed interrater and intrarater reliability, precision, validity, and
      responsiveness. RESULTS: The 26 physician investigators included representatives
      from 6 specialties and 9 countries. The interrater and intrarater reliability of
      the RI was strong (0.89 and 0.69, respectively). Correlations (construct
      validity) between the RI and PhGA were high (Spearman's r = 0.9, P < 0.0001). The
      RI was sensitive to change (discriminant validity). Following treatment, there
      was significant improvement in the RI score (mean change 10.5 [95% confidence
      interval (95% CI) 5.4-12], P < 0.001), which correlated with the change in the
      PhGA. Urgent disease and damage were captured effectively. DISCUSSION: In this
      international, multispecialty study, we observed that the RI is a valid and
      reliable disease activity assessment tool that can be used to measure response to
      therapy.

PMID- 29457384
TI  - [Clinical protocols for patellar dislocation].

PMID- 29457385
TI  - [Current status and expectations in the surgical treatment of recurrent lateral
      patellar dislocation].
AB  - Up to now, surgical treatment of recurrent lateral patellar dislocation mainly
      includes: medial patellofemoral ligament reconstruction, tibial tubercle
      osteotomy, trochleoplasty, lateral retinacular release, derotation osteotomy and
      so on . Clinical reports show that: the use of a single or combined with several
      methods have achieved ideal short to mid-term clinical outcomes. However, there
      is no consolidate criterion concerning the choices of different kinds of surgical
      ways for the treatment of individual recurrent lateral patellar dislocation.
      Meanwhile, with the wide use of MPFL reconstruction and other surgical options,
      there are more and more complications and failures that are worthy and necessary
      for us to pay attention to, even though its high success rate. The aim of this
      article is to make a systematic review of the application status of different
      surgical methods, collecting the positive results we have achieved, illuminating
      application keys of surgical techniques, guiding patient-specific therapy more
      precisely.

PMID- 29457386
TI  - [Treatment of habitual dislocation of patella with reconstruction of medial
      patellofemoral ligament combined with release of lateral retinaculum and medial
      transfer and advancement of tibial tuberosity under arthroscopy].
AB  - OBJECTIVE: To study clinical effects of triad operation including reconstruction
      of medial patellofemoral ligament, release of lateral retinaculum, Fulkerson
      tibial tubercle osteotomy, medial transfer and advancement under arthroscopy for
      the treatment of habitual dislocation of patella. METHODS: From March 2010 to May
      2016, 35 patients with habitual patellar dislocation were treated with the triad
      operation, including 14 males, 21 females, ranging in age from 18 to 38 years
      old, with an average of 25.8 years old. Twelve patients had dislocations on the
      left knee, and 23 patients had dislocations on the right knee. The changes of Q
      angle, TT-TG value and Kujala score were compared before and after operation.
      RESULTS: All the patients were followed up, and the duration ranged from 9 to 35
      months (mean, 23 months). The Q angle of male group was improved from
      preoperative (29.2+/-2.0) degrees  to postoperative (14.8+/-1.2) degrees
      (P<0.05), and the Q angle of female group was improved from preoperative(30.6+/
      2.3) degrees  to postoperative (16.7+/-1.5) degrees  (P<0.05). CT showed that the
      TT-TG value was improved from preoperative (20.3+/-2.2) mm to postoperative
      (10.3+/-1.2) mm (P<0.05). The Kujala score was improved from preoperative 47.8+/
      7.5 to postoperative 88.4+/-6.2 (P<0.05). CONCLUSIONS: The triad operation
      including reconstruction of medial patellofemoral ligament, release of lateral
      retinacular, Fulkerson tibial tubercle osteotomy, medial transfer and advancement
      under arthroscopy for the treatment of habitual dislocation of patella has good
      short-term clinical effects.

PMID- 29457387
TI  - [Multi-point fixation with absorbable cartilage screws for the treatment of
      osteochondral fracture caused by patellar instability].
AB  - OBJECTIVE: To study clinical effects of multi-point fixation with bioabsorbable
      cartilage screws for the treatment of osteochondral fracture caused by patellar
      instability. METHODS: During the period from August 2014 to Steptember 2016,
      there were 21 patients with osteochondral fracture caused by patellar
      dislocation, including 7 males and 14 females, ranging in age from 12 to 42 years
      old, with an average of 27 years old. During the operation, free fractures
      fragments of cartilage were found with a open surgery, and the patients were
      treated with fixation by absorbable cartilage screws combined with lateral
      retinaculum release and medial retinaculum shrinkage. The Lysholm scoring scale
      was used to evaluate the knee joint functions before and after operation. The
      retrospective study analyzing the data was carried out. RESULTS: All the patients
      underwent successful surgeries and were followed up with a mean period of 12
      months(ranged, 8 to 22 months). The CT and X-ray examinations were performed
      after the operation which showed the fracture fragments were on good positon. The
      exercise level in all the patients basically returned to the pre-injury level.
      The postoperative Lysholm score was 86.11+/-4.97. CONCLUSIONS: The absorbable
      cartilage nail can effectively fix the free cartilage fragments of the
      osteochondral fracture due to the patellar instability, which is a simple
      operation, and worthy of clinical promotion.

PMID- 29457388
TI  - [Case-control study of therapeutic effects between extreme lateral interbody
      fusion and conventional posterior operation for the treatment of upper lumbar
      disc herniation].
AB  - OBJECTIVE: To evaluate the clinical outcomes between extreme lateral interbody
      fusion and conventional posterior operation in the treatment of upper lumbar disc
      herniation. METHODS: Among 60 patients with upper lumbar disc herniation were
      treated with extreme lateral interbody fusion(XLIF) or conventional posterior
      operation from June 2010 to December 2014, 30 patients(19 males and 11 females)
      were treated with XLIF (XLIF group); and the other 30 patients(17 males and 13
      females) were treated with conventional posterior operation (conventional group).
      In XLIF group, the lesions occurred at T12L1 segments in 2 patients, at L1,2
      segments in 6 patients, at L2,3 segments in 10 patients, and at L3,4 segment in
      12 patients. In conventional group, the lesions occurred at T12L1 segments in 1
      patient, at L1,2 segments in 6 patients, at L2,3 segments in 8 patients, and at
      L3,4 segment in 15 patients. Operative incision lengths, time, blood loss,
      postoperative draining volume, hospital stays were recorded. Pre-and post
      operative visual analogue score(VAS) and Japanese Orthopedic Association(JOA)
      were compared between two groups. According to the image data, the intervertebral
      fusion device was observed to be displaced and the rate of interbody fusion was
      analyzed. RESULTS: All the patients were followed up, and the duration ranged
      from 12 to 48 months, with an average of 29 months. The complications included 2
      femoral nerve damage in XLIF group (postoperative recovery within 3 months) and
      superficial incision infection in conventional group(cured by anti-infection).
      There were no patients with cerebrospinal fluid leakage(CSFL), cauda equina
      injuries or functional deterioration in the nerve root of lower limbs. In the
      XLIF group: the operative time was (65.6+/-20.5) minutes, blood loss was (48.8+/
      15.3) ml, postoperative draining volume was 0 ml. In the conventional group: the
      operative time was (135.2+/-33.9) minutes, blood loss was (260.3+/-125.7) ml,
      postoperative draining volume was (207.1+/-50.2) ml. The operative time, blood
      loss, postoperative draining volume in XLIF group were less than those in the
      conventional group(P<0.05). The JOA and VAS score were significantly improved in
      both groups during the follow-up period compared with those before
      operation(P<0.05). But the difference of the JOA and VAS score between the two
      groups 1, 6, and 24 months after surgery had not significant differences(P>0.05).
      There were no significant differences in the fusion rate between the two groups 6
      and 12 months after operation(P>0.05). CONCLUSIONS: The XLIF fusion for the
      treatment of upper lumbar disc herniation has several advantages such as minimal
      invasive, stable vertebral plate, less complications and postoperative fusion
      rate, which has a better clinical effect.

PMID- 29457389
TI  - [Study on the risk factors for the misdiagnosis of femoral head osteonecrosis].
AB  - OBJECTIVE: To evaluate the status and risk factors for the misdiagnosis of
      femoral head osteonecrosis, providing the basis for accurate diagnosis of
      osteonecrosis of femoral head. METHODS: The data of 314 hospitalized patients
      were collected from March 2015 to March 2016, and the risk factors for
      osteonecrosis of femoral head were analyzed by Logistic regression model.
      Misdiagnosis was defined that the diagnosis given on the first time was different
      from that on the second time or that given by expert group with the same symptoms
      and signs. The general data, predisposing factors, time of onset, hospital
      visits, clinical manifestations, X-ray film of hip joint, MRI and other data were
      statistically analyzed. RESULTS: Total 127 patients experienced misdiagnosis (up
      to 40.8%). Among them, the patients with osteonecrosis of femoral head
      misdiagnosed as other diseases accounted for 77.2% and the patients with other
      diseases misdiagnosed osteonecrosis of femoral head accounted for 22.8%.
      Statistical analysis showed that the predisposing factors, history of
      glucocorticoid and alcohol intake, diseased lower limb, pained lower limb, hidden
      disease attack, the level of first reception hospital and expert were
      significantly related with the misdiagnosis of femoral head osteonecrosis based
      on the logistic regression model (P<0.05) . The relationship between misdiagnosis
      and gender, age, primary disease taking glucocorticoid, approach and time of
      glucocorticoid use, the type of alcohol, drinking time had no statistical
      significance(P>0.05). The Logistic regression analysis showed that the hidden
      disease attack(OR=3.059) and level of first reception expert(OR=2.778) were the
      high risk factors associated with the misdiagnosis in which the femoral head
      necrosis was misdiagnosed as other diseases(P<0.01), and glucocorticoid intake
      history was the low risk factors(OR=0.387)(P<0.05). The Logistic regression
      analysis showed that the level of first reception expert (OR=3.573) was the high
      risk factor associated with the misdiagnosis in which the other diseases were
      misdiagnosed as necrosis of femoral head. CONCLUSIONS: Misdiagnosis rate of
      femoral head necrosis is high. Hidden disease attack and low level of first
      reception expert are the high risk factors associated with the misdiagnosis in
      which the femoral head necrosis was misdiagnosed as other diseases, however,
      glucocorticoid intake history is the protective factor of misdiagnosis. Low level
      of first reception expert is the high risk factor associated with the
      misdiagnosis in which other diseases were misdiagnosed as necrosis of femoral
      head.

PMID- 29457390
TI  - [Diagnosis and treatment for posterolateral rotatory instability of the elbow].
AB  - OBJECTIVE: To study the effects of surgical reconstruction of the lateral
      ligament complex for posterolateral rotatory instability (PLRI) of the elbow
      joint. METHODS: From January 2013 to January 2015, 20 patients with
      posterolateral rotatory instability of elbow joint were treated in our
      department. There were 12 males and 8 females whose age ranged from 30 to 60
      years old, with an average age of 45.5 years old. Sixteen patients had injuries
      on the right side and 4 patients had injuries on the left side. Nine patients
      were caused by elbow dislocation and 6 cases were caused by elbow fracture. Five
      patients had no history of trauma. All the patients had closed injuries.
      According to the patient's history, physical examination and preoperative X-ray
      and MRI examination, a definite diagnosis was made. All the patients were treated
      conservatively for more than 2 months without efficacy, and they were treated
      with reconstruction of the lateral collateral ligament complex using palmaris
      longus tendon as a reconstruction graft under general anesthesia. Individual
      rehabilitation exercises were carried out according to the patient's condition.
      RESULTS: All the patients were followed up, and the duration ranged from 12 to 23
      months(mean, 16 months). There were no complications such as infection and
      obvious limitation of elbow joint. The HSS score of all the patients was improved
      from preoperative 75.2+/-8.3 to postoperative 94.1+/-5.4; and the VAS score was
      improved from preoperative 6.7+/-3.2 to postoperative 2.3+/-1.5. CONCLUSIONS: The
      lateral cubital ligament complex is the most important limiting structure for the
      posterolateral rotatory instability of the elbow joint. Reconstruction of the
      lateral ligament complex is an effective method for the treatment of
      posterolateral rotatory instability of the elbow joint.

PMID- 29457391
TI  - [Analysis on related factors of perioperative total blood loss in unilateral
      total hip arthroplasty].
AB  - OBJECTIVE: To investigate the influential factors of total blood loss during
      unilateral artificial total hip arthroplasty (THA). METHODS: From January 2014 to
      July 2016, 131 patients undergwent primary unilateral total hip arthroplasty,
      including 55 males and 76 females, ranging in age from 40 to 89 years old, with
      an average of 64.5 years old. The data of patients with unilateral total hip
      arthroplasty were collected, and the data of hemodynamics, coagulation function,
      hemoglobin and hematocrit values were recorded according to the observation data.
      The blood loss of the patients was calculated by Gross equation, and the data
      were analyzed by a statistical software. RESULTS: The total blood loss of the
      patients was significantly affected by the factors of pathogenesis and deep
      venous thrombosis of the lower limbs. The results were statistically
      significant(P<0.05). The gender, age, body mass index, prosthesis and anesthesia
      had little effects on the blood loss volume after replacement. CONCLUSIONS: The
      data in this study indicate that the volume of actual blood loss can be
      controlled by adjusting non-surgical factors such as gender, age, body mass
      index, prosthetic material, and risk factors, and surgical factors(postoperative
      complications, anesthesia).

PMID- 29457392
TI  - [Analysis on the occult blood loss after unicompartment knee arthroplasty].
AB  - OBJECTIVE: To calculate the volume of occult blood loss after unicompartment knee
      arthroplasty(UKA), and analyze its influential factors by comparing with total
      knee arthroplasty. METHODS: A retrospective study of 130 cases from July 2012 to
      July 2015 were enrolled, of which and 65 cases were UKA, and 65 cases were TKA.
      In UKA group there were 27 males and 38 females, and the mean age was (62.3+/
      4.3) years old (ranged, 50 to 82 years old). There were 14 cases older than 70
      years old, while 51 cases among 50 to 70 years old. The mean Body mass index
      (BMI) was (23.9+/-2.6) kg/m2(ranged, 18.3 to 30.1 kg/m2). In TKA group there were
      23 males and 42 females, and the mean age was (67.4+/-4.9) years old (ranged, 57
      to 81 years old). There were 34 cases older than 70 years old, while 31 cases
      among 50 to 70 years old. The mean BMI was (25.6+/-2.3) kg/m2(ranged, 20.6 to
      33.1 kg/m2). Hidden blood loss was calculated according to Gross equation, and
      the differences between the two groups including different ages and genders were
      observed subsequently. The differences of red blood cell change between two
      groups were observed dynamically postoperatively. RESULTS: Postoperative hidden
      blood loss was (375.25+/-168.09) ml, HSS score was 87.11+/-5.39 in UKA group.
      Hidden blood loss was (898.81+/-221.47) ml, HSS score was 82.23+/-3.08 in TKA
      group. The differences between the two groups were significant. There were no
      significant differences in ages and genders. There were no significant
      relationship between hidden blood loss and HSS score or BMI, while the
      differences of red blood cell change were significant on the second day, the 4th
      day and the 5th day. There was no allogenic blood transfusion in UKA group, while
      3 patients with transfusion in TKA group. CONCLUSIONS: Hidden blood loss is part
      of total blood loss after UKA, and the volume in UKA is less than that in TKA. It
      could be compensated by the body and rarely affect the knee function. The hidden
      blood is not a risk factor of transfusion.

PMID- 29457393
TI  - [Anatomical study on the reconstruction of the metacarpal bone with autogenous
      iliac crest grafting].
AB  - OBJECTIVE: To explore the similarity between the iliac crest and the metacarpal
      bone, so as to provide an anatomical basis for the reconstruction of the
      metacarpal bone of the hand with the iliac crest grafting. METHODS: There are 16
      upper limb specimens and 10 pelvic specimens. The morphological features of the
      second, third, fourth and 5th metacarpal bones and iliac crest were observed. The
      following indexes were measured: arc height and length of metacarpal head
      articular surface, volar-dorsal metacarpal diameter, ulnoradial diamater, arc
      height and length of iliac crest, and inner and outer diameter. The obtained data
      were statistically analyzed to compare the morphological, structural features,
      arc length and diameter length of each metacarpal bone and iliac crest. RESULTS:
      The arc length of the second metacarpal head, volar-dorsal metacarpal diameter,
      arc height, and the ulnoradial diameter are 22.040(21.425, 23.085) mm, (14.034+/
      0.465) mm, 4.185 (4.113, 4.598) mm, and (12.227+/-0.414) mm respectively. The arc
      length of the third metacarpal head, volar-dorsal metacarpal diameter, arc
      height, and the ulnoradial diameter are 23.430(22.743, 24.153)mm, (14.316+/
      0.430) mm, 4.235(4.170, 4.670) mm, and (12.382+/-0.425) mm respectively. The arc
      length of the fourth metacarpal head, volar-dorsal metacarpal diameter, arc
      height, and the ulnoradial diameter are 21.960 (21.245, 22.285) mm, (12.382+/
      0.288) mm, 4.125 (4.030, 4.305) mm, and (11.991+/-0.362) mm respectively. The arc
      length of the fifth metacarpal head, volar-dorsal metacarpal diameter, arc
      height, and the ulnoradial diameter are 20.030 (19.668, 20.148) mm, (11.807+/
      0.358) mm, 4.015(3.880, 4.205) mm, and (11.659+/-0.399) mm respectively. The
      inner and outer diameter of the iliac crest is 14.350 (13.660, 14.739) mm, and
      the arc length and height are (22.930+/-0.701) mm and (4.520+/-0.184) mm
      respectively. The difference between the volar-dorsal metacarpal diameter of the
      second metacarpal head and the inner and outer diameter of the iliac crest has no
      significant; while the volar-dorsal metacarpal diameter of the third, fourth and
      fifth metacarpal heads are apparently longer and shorter than the inner and outer
      diameter of the iliac crest, respectively. The differences are statistically
      significant. The differences between arc length of the iliac crest and arc length
      of the second, fourth and fifth metacarpl head are statistically significant.
      However, the difference of arc length between the third metacarpal head and the
      ilium, as well as the difference of arc height between the second and third
      metacarpal heads and the iliac crest have no statistical significances, while the
      arc height of the fourth and fifth metacarpal heads are obviously smaller than
      that of the iliac crest. CONCLUSIONS: Autologous iliac crest is similar with
      metacarpal bone in anatomy, which might be a suitable donor for metacarpal bone
      transplantation.

PMID- 29457394
TI  - [Clinical research on suture anchor fixation for the treatment of avulsion
      fracture of tibial intercondylar eminence under arthroscopy].
AB  - OBJECTIVE: To evaluate the early clinical effects of suture anchor fixation for
      the treatment of avulsion fracture of tibial intercondylar eminence under
      arthroscopy. METHODS: From July 2012 to January 2015, 22 patients with the
      avulsion fracture of tibial intercondylar eminence were treated with arthroscopic
      suture anchor fixation. There were 12 males and 10 females, with an average age
      of 22.8 years old(ranged, 18 to 33 years old). Nine patients had the fractures in
      the right knee and 13 patients had the fractures in the left knee. The mean
      duration from injury to surgery was 6.8 days(ranged, 3 to 11 days). According to
      the improved Meyers-McKeever classification, 13 cases were type II, 7 cases were
      type III, and 2 cases were type IV. The clinical outcomes were evaluated by the
      range of motion, the Lysholm score, the IKDC 2000 subjective knee score, the
      axial shift test, and the anterior drawer test. RESULTS: All the incisions healed
      by first intention, and no complications occurred. All the patients were followed
      up, and the mean duration was 32.8 months (ranged, 18 to 42 months). The knee
      range of motion was improved from preoperative (49.37+/-7.69)  degrees  to
      (126.38+/-5.58)  degrees at the latest follow-up(P<0.01). Lysholm score was
      improved from preoperative 43.4+/-5.6 to 79.2+/-6.2 at the latest follow
      up(P<0.01). And the IKDC 2000 score was improved from preoperative 52.6+/-6.2 to
      81.4+/-5.7 at the latest follow-up(P<0.01). At the latest follow-up, the patient
      underwent physical examination. One patient had a positive result of axial shift
      test at the 18th month after operation with grade II laxity of anterior cruciate
      ligament. One patient had a weakly positive result of anterior drawer test at the
      24th month after operation. CONCLUSIONS: Absorbable suture anchor fixation for
      the treatment of avulsion fracture of tibial intercondylar eminence under
      arthroscopy can provide accurate reduction and stable fixation, which can be
      applied to treat all types of fractures including comminuted fracture, and it is
      not necessary to remove the implant in the second operation.

PMID- 29457395
TI  - [Effects of patient-controlled infraclavicular brachial plexus block for
      postoperative pain and surgical efficacy in patients with terrible tyriad of the
      elbow].
AB  - OBJECTIVE: To study the effects of ultrasound guided inter-scalene brachial
      plexus block and patient-controlled infraclavicular brachial plexus block for
      postoperative pain and surgical efficacy in patients with terrible tyriad of the
      elbow. METHODS: From March 2015 to August 2016, 60 patients with terrible tyriad
      of the elbows were treated in Ningbo No.6 Hospital with ASA I to II internal
      fixation. There were 32 males and 28 females, ranging in age from 16 to 70 years
      old, with a mean age of (55.6+/-18.2) years old. All the patients were divided
      into two groups(30 cases in each group): controlled intermuscular groove brachial
      plexus block (group C), infraclavicular brachial plexus block(group I). All
      catheters were placed using ultra-sound visualization and injected 0.33%
      ropivacaine 30 ml preoperatively. After regaining consciousness, all patients
      connected the electronic pump. The solution contained 0.2% ropiva-caine and the
      pump was setup to deliver a 5 ml bolus dose, with a 15 min lock out interval and
      background infusion at 5 ml/h. Both analgesia lasted until 5 d after operation.
      The patients underwent rehabilitation exercise everyday for 5 consecutive days
      starting from 24 h after operation.VAS score was recorded at 24 h, 48 h, 72 h and
      4 d, 5 d after operation during rest and rehabilitation exercise time. The elbow
      articular range of motion and Mayo elbow performance score (MEPS) were recorded
      at 6 d after operation. Catheter-related adversereactions (such as oozing from
      the insertion site, obstruction, prolapse) were recorded. RESULTS: The success
      rate of blockade was 100% during insertion in both groups. Compared with group C,
      the VAS score at 3 d during rest time and 3, 4, 5 d after operation during
      rehabili-tation exercise were decreased(2.5+/-0.5 vs. 3.8+/-1.1, 3.0+/-0.4 vs.
      5.0+/-0.9, 2.5+/-0.4 vs. 4.5+/-1.2, 2.1+/-0.3 vs. 4.1+/-1.0, P<0.05). The elbow
      articular range of motion and MEPS were increased(-2.19+/-18.01) degrees  vs.(
      8.19+/-12.16) degrees , (45.15+/-11.20) degrees  vs. (22.15+/-7.02) degrees ,
      (19.06+/-6.75) degrees  vs. (9.10+/-2.48) degrees , (17.08+/-5.18) degrees  vs.
      (10.12+/-3.15) degrees , (80.80+/-9.50) points vs. (64.90+/-11.21) points. The
      incidence of insertion site, obstruction, prolapse was 15, 5 and 10 cases
      respectively in group C, but without any catheter-related adverse reactions
      happened in group I (P<0.05). CONCLUSIONS: Patient-controlled infraclavieular
      brachial plexus block can be effectively used for postoperative pain after
      fixation for terrible tyriad of the elbows, and it can increase surgical outcome.

PMID- 29457396
TI  - [Ultrasonic analysis on the effect of strengthening exercise with strong tendon
      on lumbosacral multifidus muscles].
AB  - OBJECTIVE: To study effects of strengthening exercise with strong tendon on the
      lumbosacral multifidus muscle. METHODS: Among 30 healthy volunteers, there were
      21 males and 9 females, with an average age of(31.30+/-6.48) years old(ranged, 25
      to 55 years old). The mean BMI was (21.70+/-1.95) kg/m2(ranged, 18.1 to 24.9
      kg/m2). The ultrasonic image was used to analyze the thickness of lumbosacral
      multifidus(LM) under the follow conditions: supine position, and supine position
      with leg lifting 30 degrees , 60 degrees , 90 degrees ; seat and hip flexion,
      flexion to limit position, front to limit position with both hands climbing and
      strengthening the kidneys and the waist. RESULTS: The average lumbosacral
      multifidus thickness was (16.867+/-2.460) mm, (19.010+/-2.510) mm, (22.477+/
      2.220) mm, and(27.593+/-2.370) mm respectively in supine position with leg
      lifting 0 degrees , 30 degrees , 60 degrees , 90 degrees . There were statistical
      differences(F=423.619, P<0.05). The average lumbosacral multifidus thickness was
      (25.810+/-2.440) mm, (15.677+/-2.130) mm, and (15.533+/-2.110) mm respectively in
      seat and hip flexion, flexion to limit, front to limit positions with both hands
      climbing and strengthening the kidneys and the waist. There were statistical
      differences(F=597.789, P<0.05). CONCLUSIONS: When healthy volunteers in Shi's
      Orthopedics strengthen muscle exercises training, multifidus thickness is
      increased with the increasing of leg degree, reduced with the increasing of the
      flexion degree. It can change the stretching state of multifidus muscle by a
      specific training, so as to achieve the purpose of training the multifidus
      muscle.

PMID- 29457397
TI  - [Reconstruction of medial patellofemoral ligament with Tightrope button fixation
      on the femoral side for the treatment of traumatic patellar dislocation].
AB  - OBJECTIVE: To explore the operating procedures and therapeutic effects of medial
      patellofemoral ligament reconstruction with Tightrope(Arthrex, FL, USA) button
      fixation at lateral femoral cortex. METHODS: From May 2014 to July 2016, 9
      patients with traumatic patellar dislocation were treated. There were 5 males and
      4 females, ranging in age from 16 to 47 years old, with an average of 23.7 years
      old. All the patients underment arthroscopic lateral retinaculum release and
      joint debridement first. Then the medial patellofemoral ligament was
      reconstructed by using a semitendinosus autograft. The ends of semitendinosus
      were pulled into two patellar tunnels respectively, knotted and fixed at the
      lateral side of patella. The semitendinosus loops were suspended and fixed
      through femoral tunnel with Tightrope button. The knee was fixed to about 60
      degree and the tension of MPFL was adjusted by pulling Tightrope wire under
      arthroscopic observation. Two patients received superomedial transfer of tibial
      tuberosity on account of TT-TG >=20 mm. RESULTS: All the patients were followed
      up, and the duration ranged from 6 to 23 months, with an average of 13.6 months.
      Patellar stability was re-obtained in all patients. No dislocation re-currenced
      during the follow-up period. The Kujala score(scoring of patellofemoral
      disorders) was improved at the latest follow-up compared with that before
      operation. All the patients returned to routine life. CONCLUSIONS: Reconstruction
      of medial patellofemoral ligament with the Tightrope button fixation on the
      femoral side for the treatment of traumatic patellar dislocation is effective and
      economic. The method make the MPFL tension adjustable during the reconstuction
      under arthroscopy. The MPFL tension should be adjusted at 60 degree flexion of
      knee in order to avoid making tension level too high.

PMID- 29457398
TI  - [Clinical outcome analysis on using extensor digitorum communis splitting
      approach for the treatment of radial head fractures].
AB  - OBJECTIVE: To explore the clinical outcomes of internal fixation or replacement
      for the treatment of radial head fractures through the extensor digitorum
      communis splitting approach. METHODS: From July 2012 to May 2015, 25 patients
      with radial head fractures were reviewed. There were 17 males and 8 females,
      ranging in age from 20 to 67 years old, with a mean age of 39 years old. Twenty
      one patients were treated with reconstruction of plate internal fixation, and 4
      patients were treated with radial head replacement. According to Mason
      classification, 19 cases were type II and 6 cases were type III. All the patients
      underwent internal fixation or replacement through the extensor digitorum
      communis splitting approach. The patients were followed up clinically and
      radiographically until the beginning of fracture union and the entrance of
      function recovery of elbow motion into a plateau. The functional status of the
      elbow was evaluated using the Mayo Elbow Performance Index(MEPI). Radiographic
      signs of post-traumatic arthritis were rated according to the Broberg and Morrey
      system. RESULTS: All the patients were followed up, and the average duration was
      29 months (ranged, 12 to 56 months). The average range of flexion and extension
      was 120 degrees , the extension was limited by 10 degrees , and the flexion was
      135 degrees . The average forearm rotation range was 142 degrees , pronation was
      75 degrees , supination was 67 degrees . The mean MEPI was 93+/-7(ranged, 80 to
      100 scores); according to the MEPI scoring criceria, 19 patients got an excellent
      functional result, 6 good. According to the Broberg and Morrey systems of
      traumatic arthritis, 19 patients were in grade 0, 6 in grade 1, and no patients
      in grade 2 or 3. No patients with nonunion of the radial head and failure of
      internal fixation were found. There were no complications of nerve or vascular
      injuries, and obvious limitation of elbow rotation. Heterotopic ossification
      around the elbow occurred in 4 cases, but the motion was not significantly
      limited. There were no complications such as prosthesis loosening and infection
      in 4 cases after radial head prosthesis replacement. CONCLUSIONS: The extensor
      digitorum communis splitting approach is an effective exposure method for
      internal fixation or replacement in the treatment of radial head fractures.

PMID- 29457399
TI  - [Osseous bridge resection for the treatment of adult talocalaneal coalitions
      without arthritis].
AB  - OBJECTIVE: To analyze clinical outcomes of osseous-bridge resection for the
      treatment of adult symptomatic talocalcaneal coalitions without arthritis.
      METHODS: The clinical data of 12 patients (15 feet) with symptomatic
      talocalcaneal coalitions without arthtitis from January 2013 to June 2016 were
      respectively analyzed. All cases were secondary talocalcaneal coalition. There
      were 9 males (11 feet) and 3 females (4 feet) with a mean (26.6+/-3.3) years old
      (ranged, 18 to 33 years old). According to the Rozansky classification, there
      were 4 (6 feet) type I, 3 (3 feet) type II, 2 (2 feet) type III, 1 (1 feet) type
      IV, and 2 (3 feet) type V. All patients received coalition resection and
      interposition of fat graft. Complication, recurrence and range of motion was
      regularly recorded after operation. Clinical efficacy was evaluated according to
      the visual analogue scale (VAS) and the American Orthopedic Foot and Ankle
      Society (AOFAS) ankle hindfoot scale. RESULTS: All patients were followed up for
      an average duration of (28.7+/-18.3) months (ranged, 12 to 48 months). All the
      incisions were primarily healed. There were no wound necrosis, infection,
      neurovascular or tendon injuries. Range of motion was improved in 13 feet. All
      patients returned back to work. Recurrence happened in 1 case 2 years after
      surgery, the patient received a secondary coalition resection. At the latest
      follow-up, VAS was 2.1+/-0.8 and AOFAS score was 82.7+/-7.2, were siginificantly
      improved when compared with the preoperative scores(8.2+/-0.7, t=6.233, P<0.01;
      48.4+/-6.8, t=5.747, P<0.01). CONCLUSIONS: For adult patients with symptomatic
      talocalcaneal coalitions without arthritis, simple coalition resection could
      provide good clinical outcomes with minimal complications.

PMID- 29457400
TI  - [A case report of reversed and separated elbow dislocation with humeral fractures
      of medial and lateral condyle].

PMID- 29457401
TI  - [Popliteal pseudoaneurysm and arteriovenous fistula after multiple ligament
      injuries of knee joint: a case repor].

PMID- 29457402
TI  - [Clinical study on negative pressure closed drainage combined with vancomycin
      loaded calcium sulfate and autogenous bone in the treatment of chronic
      osteomyelitis].
AB  - OBJECTIVE: To study the clinical effects of negative pressure closed drainage
      combined with vancomycin loaded calcium sulfate and autogenous bone in the
      treatment of chronic osteomyelitis. METHODS: From June 2013 to December 2016,
      there were 35 cases of chronic osteomyelitis patients in our department,
      including 23 males and 12 females, ranging in age from 11 to 65 years old, with
      an average of 34 years old. The course of disease ranged from 8 to 46 months,
      with an average of 26 months. All patients were chronic osteomyelitis caused by
      open wounds. The lesions had recurrent redness and swelling and purulent skin
      perforation. Thirty-two patients had positive results in bacterial culture of
      sinus secretions, and 3 patients had negative results. Imaging examination showed
      the lesions of bone destruction, bone defects, surrounded by bone hyperplasia
      sclerosis. At the first stage, complete debridement was performed to remove
      necrotic tissues and inflammatory tissues; and the dressing of negative pressure
      closed drainage was used to completely cover the wound so as to promote the
      repair of the wound. At the second stage, the vancomycin loaded, calcium sulfate
      and autogenous iliac cancellous bone were mixed into the bone graft complex to
      evenly fill the lesions. The healing of the wound was observed and X-ray
      examination of the lesion was carried out to observe the absorption of calcium
      sulfate and the growth of new bone. RESULTS: Twenty-six patients underwent
      debridement and negative pressure closed drainage on time, 6 patients 2 times,
      and 3 patients 3 times. Thirty-two patients had incisions healed with grade A; 2
      patients had incisions healed with grade B, and got completely healing after anti
      infection, and wound dressing treatment; 1 patient had an incision healed with
      grade C, and got normal healing after re-debridement at the 4th week after
      operation. All patients did not have skin redness and ulceration again. X-ray
      imaging showed that the implanted calcium sulphate was absorbed gradually around
      4 weeks, new bone was formed at 8 weeks, and bone defects in the lesions area
      were healed completely at 6 months to 2 years. CONCLUSIONS: Negative pressure
      closed drainage combined with vancomycin loaded calcium sulfate and autogenous
      bone in the treatment of chronic osteomyelitis is a good and reliable method,
      worthy of clinical promotion.

PMID- 29457403
TI  - [Traditional manipulative reduction and percutaneous elastic intramedullary nail
      fixation for the treatment of proximal humeral fractures in children].
AB  - OBJECTIVE: To study clinical effects and safety of traditional manipulative
      reduction and percutaneous elastic intramedullary nail fixation for the treatment
      of proximal humeral fractures in children. METHODS: From October 2012 to May
      2016, 65 patients with proximal humeral fractures were treated with traditional
      manipulative reduction and percutaneous elastic intramedullary nail fixation.
      There were 52 boys and 13 girls, ranging in age from 7 to 14 years old, with an
      average age of 11.2 years old. Twenty-three patients had injuries on the left
      side, and 42 patients had injuries on the right side. There were 13 cases of
      oblique fracture, 49 cases of transverse fracture, and 3 cases of comminuted
      fracture. All the patients had closed, obviously displaced fractures, without
      vascular and nerve injuries. The duration from injury to treatment ranged from 20
      minutes to 5 days, with a mean of 3 days. The fracture healing and complications
      were observed after operation, and the curative effect was evaluated by Neer
      shoulder function score. RESULTS: The operation time ranged from 30 to 40
      minutes, with a mean of 35 minutes; intraoperative blood loss ranged from 5 to 10
      ml, with a mean of 6.5 ml. All the patients were followed up, and the duration
      ranged from 12 to 28 months, with an average of 18 months. All the fractures
      healed. According to the Neer evaluation system, 59 patients got an excellent
      result, 5 good and 1 fair. Four patients had a small amount of secretions on the
      tail of the needle; 2 patients had skin irritation; 1 patient had partial
      withdrawal of the nail, and the skin in all the patients healed after taking out
      the nail. No patients had nonunion fractures due to the broken nails and loosen
      screws, and no vascular or nerve injuries occurred. CONCLUSIONS: Traditional
      manipulative reduction and percutaneous elastic intramedullary nail fixation for
      the treatment of proximal humeral fractures in children has the advantages of
      less trauma, quicker recovery, less complications and simple operation.

PMID- 29457404
TI  - [Perioperative and drug management of patients with rheumatoid arthritis treated
      with joint replacement].
AB  - Rheumatoid arthritis (RA) is a most common inflammatory joint disease with direct
      invasion of joint synovial membrane, cartilage and bone. Currently, although the
      RA mitigation drugs are being improved continously, but these drugs only can
      delay the development of joint dysfunction. Total hip arthroplasty or total knee
      arthroplasty(THA or TKA) has become the only choices for patients with advanced
      RA, and the joint function and deformity of the patients after surgical treatment
      can be improved to some extent. However, the progression of RA has a direct
      effect on the long-term clinical effect of the surgery, and how to improve
      perioperative management, and combine the joint replacement surgery and drug
      therapy effectively, have become the focus of attention in clinical doctors. This
      article intends to summarize the current situation of domestic and foreign
      management of usage of pre-operative drugs, operation skills, prosthesis
      selection, postoperative treatment, rehabilitation and complications, so as to
      improve the long-term efficacy of joint replacement.

PMID- 29457405
TI  - [Morphology characteristics of sural bean bone and it's role in knee joint
      diseases].
AB  - Fabella is a common sesamoid bone. In recent years, people have paid more
      attention to its anatomic location, distribution characteristics in crow,
      importance in stabilizing knee joint and related diseases. This article reviews
      the anatomy, distribution and the relationship between the calf bone and the knee
      joint diseases, so as to strengthen the attention of the bones in the diagnosis
      and treatment of knee diseases.

PMID- 29457406
TI  - [Challenges in management of complex tibial plateau fracture].

PMID- 29457407
TI  - [Analysis of the treatment of posterolateral tibial plateau fracture with three
      different methods].
AB  - OBJECTIVE: To analyze and compare the efficacy of surgical approaches and
      fixations of anterolateral approach, lateral approach and posterolateral approach
      in treating posterolateral tibial plateau fracture. METHODS: A retrospective
      study of 44 cases from May 2010 to July 2014 were enrolled, of which there were
      21 males and 23 females, and the mean age was 42.5 years old (ranged, 26 to 61
      years). All the cases were divided into 3 groups according to the surgical
      approach, group A was anterolateral approach (19 cases), group B was lateral
      approach (15 cases), group C was posterolateral approach (10 cases). Operative
      time and bleeding volum were compared and the knee function was observed.
      RESULTS: The mean operative time of group A was (91.3+/-10.4) min, and the
      bleeding volum of which was (175.3+/-20.3) ml. The mean operative time of group B
      was(86.6+/-9.2) min, and the bleeding volum of which was(155.8+/-18.2) ml. The
      mean operative time of group C was (109.5+/-10.8) min, and the bleeding volum of
      which was(235.9+/-29.1) ml. There were significant differences in operative time
      and bleeding volum between group C and the other two groups(P<0.05). The mean
      follow-up time was 14.9 months (ranged, 10 to 35 months), and the HSS score of
      last follow-up was 89.6+/-7.5 (group A), 90.2+/-6.4(group B), 88.9+/-5.1 (group
      C). There were no significant differences in groups(P>0.05). CONCLUSIONS: The
      operative time of posterolateral approach was longer than anterolateral approach
      or lateral approach, as well as the bleeding volum which was higher in
      posterolateral approach, while no significant difference of the knee function was
      observed in these 3 different approaches.

PMID- 29457408
TI  - [Double-plate fixation via combined approaches for the treatment of old tibial
      plateau fractures of Schatzker type IV].
AB  - OBJECTIVE: To explore the clinical efficacy of double-plate fixation for the
      treatment of old tibial plateau fractures with Schatzker type IV through anterior
      midline and posteromedial approaches. METHODS: From July 2013 to July 2015, 15
      patients with old tibial plateau fractures were treated with internal fixation
      using locking reconstructive plate for the posteromedial fragment and anatomical
      locking plate for anteromedial fragment through antero midline and posteromedial
      approaches. There were 9 males and 6 females, with an average age of 49.2 years
      old (ranged, 21 to 61 years old). Eight patients had injured in the left side and
      7 in the right side. According to Schatzker classification, all patients were
      type IV. The mean interval from injury to operation was 26.5 days (ranged, 21 to
      65 days). The main clinical symptoms before operation were knee joint swelling,
      pain, deformity and limitation of motion. The X-ray and CT confirmed the fracture
      type. The indexes such as tibial plateau tibial shaft angle (TPA), femoral tibial
      angle (FTA) and posterior slope angle (PSA) were compared between immediate
      postoperation and final follow-up using postoperative X-ray film. The knee
      functions were evaluated using the HSS (Hospital for Special Surgery) knee score
      system. RESULTS: Two patients had incision complications which healed by correct
      treatment, 1 patient had traumatic arthritis. All patients were followed up for
      mean 16.6 months (ranged, 13 to 24 months). No infections, deep venous
      thrombosis, implant loosening and breakage, fragment displacement, plateau
      surface collapse and bone nonunion found. The bone union time ranged from 3 to 8
      months (mean 6.07 months) after operation. The average immediate postoperative
      value of TPA, FTA and PSA were(86.81+/-1.67) degrees , (168.00+/-3.29) degrees 
      and(10.20+/-1.47) degrees  respectively; and(86.47+/-1.67) degrees , (168.53+/
      3.03) degrees  and (10.54+/-1.21) degrees  respectively at the final follow-up
      evaluation, showing no statistical differences(P>0.05). According to the HSS
      score system, 26.33+/-3.86 in pain, 20.00+/-1.79 in function, 16.00+/-1.55 in
      range of motion, 8.67+/-0.94 in muscle strength, 8.53+/-1.67 in flexion
      deformity, 9.33+/-0.94 in joint stability, and the total mean score was 88.86+/
      8.92. The outcomes were excellent in 10 cases, good in 4, and fair in 1.
      CONCLUSIONS: Double-plate fixation via combined anterior midline and
      posteromedial approaches is an ideal surgical method for old tibial plateau
      fractures with Schatzker IV type, showing satisfactory exposure, reliable
      reduction and fixation, and benefiting for early functional exercise. The short
      term clinical results was satisfactory.

PMID- 29457409
TI  - [Analysis of risk factors of infection for complex tibial plateau fractures after
      operation].
AB  - OBJECTIVE: To analyze the risk factor of infection for complex tibial plateau
      fractures after operation. METHODS: Totally clinical data of 293 patients with
      complex tibial plateau fractures underwent open reduction and internal fixation
      were retrospectively analyzed from September 2010 to March 2015, including 199
      males and 94 females, ranging in age from 17 to 80 years old with an average of
      47.3 years old. The possible risk factors such as gender, age, smoking, diabetes,
      type of fracture(open/closed), classification of open fracture(Gustilo-Anderson
      classification), classification of soft tissue injury in closed fracture
      (Tscherne-Gotzen classification), fracture classification(Schatzker V/VI),
      osteofascial compartment syndrome, ASA score, anesthesia, timing of surgery,
      operative time(<=150 min/>150 min), surgical approach, combined approach or not,
      internal fixation site were studied. The multivariate Logistic regression model
      was used to analyze the risk factors. RESULTS: Twelve patients were infected of
      all 293 patients after operation, the infection rate was 4.10%. Univariate
      analysis showed that fracture type(chi 2 =14.496, P=0.001), fracture
      classification(chi2=4.560, P=0.033), osteofascial compartment
      syndrome(chi2=15.631, P=0.001), operative time(chi2=11.233, P=0.001) were
      correlated with complex tibial plateau fractures postoperative infection.
      Multivariate analysis showed that open fractures(chi2=9.696, P=0.002) and
      osteofascial compartment syndrome(chi2=9.119, P=0.003) were complex tibial
      plateau fracture risk factors for infection after operation. CONCLUSIONS: Open
      fractures and osteofascial compartment syndrome are risk factor of complex tibial
      plateau fracture for infection after operation. While through debridement for
      open fracture patients, early diagnosis and promt treatment for osteofascial
      compartment syndrome could reduce incidence of infection.

PMID- 29457411
TI  - [Effect of hip fracture at different sites in elderly patients on prognosis].
AB  - OBJECTIVE: To determine the effect of site of fracture on the prognosis for
      patients of elderly hip fracture. METHODS: From January 2012 to December 2014,
      667 patients with hip fractures were divided into femoral neck fracture group and
      intertrochanteric fracture group according to the site of fracture. There were
      304 cases of intertrochanteric fracture, including 96 males and 208 females, with
      an average age of (80.33+/-7.94) years old. There were 217 cases of femoral neck
      fracture, including 74 males and 143 females, with an average age of (79.82+/
      9.33) years old. Patients' data, mortality and activities of daily living were
      compared between two groups. RESULTS: There were no significant differences in
      age, gender, comorbidity, ASA classification, and anesthesia between two groups,
      but the time of admission to surgery, duration of operation, blood loss of intra
      operative, volume of drainage, and the average of transfusion were shown to have
      significant differences. The levels of White blood cell count (WBC) for
      intertrochanteric fracture group were shown to be higher than that of femoral
      neck fracture patients at admission, 1, 3 and 5 days after operation. The levels
      of hemoglobin, and albumin for intertrochanteric fracture were lower than that of
      femoral neck fracture patients at all period of time. The mortality of
      intertrochanteric fracture group during hospitalization, 1, 3, 6, and 12 months
      were higher than that of femoral neck fracture, but did not reach significant
      difference. In patients who survived, the scores of ADL for femoral neck fracture
      were higher than that of intertrochanteric fracture at discharge, 1, 3 months
      after operation, but there was no significant difference for ADL at 6 and 12
      months between two groups. CONCLUSIONS: The response of stress for
      intertrochanteric fracture were more than femoral neck fracture, but the
      mortality was similar than that of femoral neck fracture after excluding the
      influence of age, sex, comorbidity, and other factors. Compared to
      intertrochanteric fracture, the femoral neck fracture patients had a better
      functional recovery during early stage, and the two groups reached a similar
      functional recovery at 1 year after operation.

PMID- 29457410
TI  - [Effect of admission blood urea and creatinine levels on mortality in elderly
      patients with hip fracture].
AB  - OBJECTIVE: To observe the effect of admission blood urea and creatinine levels on
      mortality in elderly patients with hip fracture. METHODS: Form January 2013 to
      December 2014, 767 elder patients with hip fracture were treated in our hospital
      including 253 males and 514 females, aged from 65 to 96 years old with an average
      of(75.67+/-6.81) years old. According blood urea and creatinine levels, the 767
      hip fracture patients were divided into four groups as follow: group A(blood
      urea>=5 mmol/L, creatinine>=70 MUmol/L); group B (blood urea>=5 mmol/L,
      creatinine<70 MUmol/L); group C (blood urea<5 mmol/L, creatinine>=70 MUmol/L);
      group D(blood urea<5 mmol/L, creatinine<70 MUmol/L). In group A, there were 211
      patients including 70 males and 141 females, aged from 65 to 95 years old with an
      average of(80.24+/-6.51) years old; in group B, there were 355 patients including
      125 males and 230 females, aged from 65 to 93 years old with an average
      of(78.46+/-7.09) years old; in group C, there were 36 patients including 11 males
      and 25 females, aged from 65 to 95 years old with an average of (77.83+/-6.78)
      years old; in group D, there were 165 patients including 47 males and 118
      females, aged from 65 to 96 years old with an average of (76.71+/-8.35) years
      old. The survivals and dead patients in four groups were collected and in
      hospital mortality rate, 3-month, 12-month and 18-month mortality rate of
      patients were calculated. COX regression analysis was performed on these data,
      and clinical significance of serum urea and creatinine at admission in the
      elderly patients was researched. RESULTS: All 767 hip fracture patients were
      followed up from 18 to 24 months with an average of (21.33+/-1.25) months, 159
      patients were died in follow up period. The in-hospital mortality rate in 3
      month, 12-month and 18-month mortality rate of the patients with high blood urea
      and high blood creatinine (urea>=5 mmol/L, creatinine>=70 MUmol/L) were 2.37%,
      9.95%, 16.11% and 26.07%, and were higher than other three groups respectively.
      COX regression analysis revealed that the independent predictors effecting the
      mortality rate included age [P=0.000, OR=1.375, 95%CI(1.155, 1.637)], blood urea
      at admission [P=0.000, OR=1.375, 95%CI(1.155, 1.637)], and blood creatinine at
      admission[P=0.037, OR=1.213, 95%CI(1.121, 1.484)]. CONCLUSIONS: Elderly hip
      fracture patients with high serum urea and high serum creatinine at admission
      indicate higher fatality rate. Age, serum urea and serum creatinine at admission
      were independent predictors of fatality rate of elderly hip fracture patients.

PMID- 29457412
TI  - [linical application of personalized 3D printing-guided template of
      intramedullary lag screw insertion on lateral superior ramous of pubic].
AB  - OBJECTIVE: To evaluate the efficacy and advantages of personalized 3D printing
      guided template of lateral superior ramous of pubic intramedullary lag screw.
      METHODS: From July 2015 to December 2016, 20 patients with the superior and
      inferior ramous of pubis fracture were treated with lag screws placement. All the
      patients were divided into test group(with guided template) and control
      group(with general operation). There were 7 males and 3 females with an average
      age of (46.20+/-3.03) years old in test group and 6 males and 4 males with
      (48.50+/-2.25) years old in control group. There were 6 cases and 5 cases of
      superior and inferior branches fractures of pubic on the left side and 4 cases
      and 5 cases on the right side in two groups respectively. The operation time,
      perspective times and bleeding loss were compared between two groups. RESULTS:
      The test group and the control group had no statistically significant relative to
      gender, age, fracture classification. The average time of surgery, average
      intraoperative fluoroscopy times, mean blood loss in test group were (31.0+/-5.3)
      min, (3.5+/-2.1) times, (75.6+/-10.5) ml respectively, and in control group
      were(55.0+/-6.8) min, (27.6+/-3.2) times, (85.5+/-12.5) ml respectively. There
      were significant Statistical differences between two groups(P<0.05) in average
      operation time and average fluoroscopy times, however, mean blood loss had no
      significant differences between two groups(P>0.05). CONCLUSIONS: The personalized
      guide template based on 3D printing technology could realize precise placement of
      the lateral intramedullary lag screw fixation in the superior branch of pubic,
      also could save the operation time and reduce the times of radiation exposure of
      patients and surgeons.

PMID- 29457413
TI  - [Clinical observation of proximal femoral anti-rotation nail for the treatment of
      femoral intertrochanteric fracture].
AB  - OBJECTIVE: To explore the curative effect and the recessive loss of blooding of
      PFNA for the treatment of intertrochanteric fractures of femur. METHODS: From
      January 2012 to January 2015, a total of 49 patients with intertrochanteric
      fractures of femur were treated with proximal femoral anti-rotation nail
      including 41 males and 8 females with an average age of 79 years old ranging from
      65 to 91 years old. According to the modified Evans type, 1 case was type I, 12
      cases were type II, 36 cases were type III. All cases were fresh fractures.
      Patients had hip pain, movement limited, joint swelling, bruising, extorsion
      deformity, X-ray and CT examination showed completely fractures. All patients
      were treated by closed reduction and PFNA internal fixation. Three comminuted
      fractures using closed reduction were not satisfied, then were treated by limited
      PFNA fixation after open reduction. RESULTS: The patients' incision got the grade
      A healing, no complications such as infection and internal fixation failure
      happened. All patients were followed up from 6 to 36 months (means 22 months).
      The pain VAS score decreased from preoperative 7.70+/-1.97 to 1.00+/-0.26 at 6
      months after operation(P<0.01). Harris hip score improved from preoperative
      8.70+/-4.19 to 91.70+/-5.31 at 6 months after operation(P<0.01). The outcome at 6
      months after operation was excellent in 34 cases, good in 7, poor in 1. The
      fracture healing time was from 8 to 16 weeks with an average of 12 weeks after
      operation. One patient with osteoporosis, crushing broken, poor compliance,
      associated with schizophrenia at the same time, appeared with the displacement of
      the femoral greater trochanter, with conservative treatment for healing.
      CONCLUSIONS: Intertrochanteric fractures of femur are common in the elderly
      trauma, in pain relief, recovery of hip function, to provide quality of life for
      the patients, PFNA achieved satisfactory effect, but its existence is worth to
      pay close attention to the recessive loss of blood.

PMID- 29457414
TI  - [Clinical research of popliteal cyst excision combined with debridement of the
      knee under arthroscopy with local anesthesia].
AB  - OBJECTIVE: To evaluate the clinical effects of popliteal cyst excision combined
      with debridement of the knee under arthroscopy with local anesthesia. METHODS:
      From February 2009 to August 2014, 52 patients with popliteal cysts were treated
      in our hospital, including 34 males and 18 females with an average age of 43.6
      years old ranging from 14 to 62 years old; 29 cases were on the right knee and 23
      on the left knee. Preoperative diagnosis was performed according to MRI findings
      and to determine whether other knee disorders were associated with the disease,
      52 patients were diagnosed as popliteal cyst before operation; 23 cases of simple
      meniscus injury or cartilage injury, 18 cases of osteoarthritis, 7 cases of
      cruciate ligament injury, 2 cases of gouty arthritis, 1 case of rheumatoid
      arthritis, 1 case of pigmented villonodular arthritis. The preoperative clinical
      manifestations involved knee swelling in 21 cases, knee joint pain in 16 cases,
      joint lock in 8 cases, leg weakness in 4 cases, and knee joint snapping in 4
      cases. Cyst size was 4.0 cm* 3.3 cm to 6.2 cm* 5.3 cm. According to the
      Rauschning and Lindgren standards, 1 case was grade I, 9 cases were grade II, 42
      cases were class III. The rehabilitation plan should be made according to the
      patient's specific injuries and intraoperative management. During the
      postoperative follow-up, the postoperative curative effect was evaluated by the
      standard grading of Rauschning and Lindgren of popliteal cyst. RESULTS: All the
      incisions healed by first intention, and no complications occurred. All the cases
      were followed up from 25 to 64 months (averaged 39.6 months). For the Rauschning
      and Lindgren grading, 43 cases were grade 0, 8 cases were grade I, 1 case were
      grade II. CONCLUSIONS: Local anesthesia under arthroscopy and popliteal cyst
      removal knee joint cavity debridement is effective, less trauma, quick recovery,
      short term effect is good. The recurrence rate is also low because of the primary
      disease of the knee joint is also treated. After the operation, the
      rehabilitation plan should be made according to the intraoperative treatment and
      actively trained so as to recover at an early date.

PMID- 29457415
TI  - [Preliminary study of intervention in effect of Bushen Huoxue recipe on
      calcification of lumbar vertebra cartilage endplate of the aging gerbils].
AB  - OBJECTIVE: To study the effect of Bushen Huoxue decoction on calcification of
      cartilage endplate in lumbar vertebrae. METHODS: Six healthy male gerbils with 2
      month-old were selected as normal control group, and 24 7-month-old healthy male
      gerbils were fed to 12-month-old to establish the aged gerbil model. Thirty
      gerbils were randomly divided into five groups as follow: the normal control
      group (n=6), model group (n=6, normal saline 4 ml/kg, intragastric 30 d), Bushen
      Huoxue low dose group(n=6, 1.9* 10- 3 ml/g given Bushen Huoxue recipe orally, 30
      d), Bushen Huoxue middle dose group(n=6, 3.8* 10- 3 ml/g given Bushen Huoxue
      recipe orally, 30 d), Bushen Huoxue high dose group(n=6, 7.6* 10- 3 ml/g given
      Bushen Huoxue recipe orally, 30 d), the intervention group administered for 1.36
      g from 7-month-old age, 30 d. The animals were sacrificed at the age of 2 months
      in the normal control group and 12 months of age in the other groups. The
      morphology of the lumbar vertebral cartilage endplate, the area of vascular bud,
      the ratio of non-calcified/calcified layer were analysis by HE chromosome visual
      method. The expression of type X collagen and BMPs in cartilage endplates were
      detected by rabbit monoclonal immunohistochemical staining. RESULTS: The relative
      area of the vascular buds cartilage endplate measurements showed that compared
      with the model group, middle dose group and normal control group increased
      (P<0.05), high and low dose groups all had different degrees of increase, but no
      statistical significance(P>0.05). The ratio of cartilage endplate thickness of
      non-calcified/calcified showed that compared with the model group, Bushen Huoxue
      middle dose, normal control group increased, with statistical
      significance(P<0.05), and high and low dose groups all had different degrees of
      increase, but there were no statistical significance(P>0.05). Compared with the
      model group, the expression of type X collagen in the cartilage endplate of the
      normal group, the Bushen Huoxue low, middle and high dose groups decreased, and
      had statistical significance(P<0.01); compared with the model group, the
      expression of BMPs in the normal group, Bushen Huoxue middle dose group
      increased, with statistically significant(P<0.01), while the high and low dose
      groups increased in different degrees, but there was no statistical
      significance(P>0.05). CONCLUSIONS: Bushen Huoxue prescription can delay the
      calcification of cartilage endplate in the process of aging, suggesting that it
      can be used as a preventive medicine for early disc degeneration.

PMID- 29457416
TI  - [Meta-analysis of the efficacy and safety of PFNA and InterTAN for the treatment
      of intertrochanteric fractures].
AB  - OBJECTIVE: To system evaluate the clinical effect and safety of PFNA and InterTAN
      internal fixation methods for femoral intertrochanteric fracture. METHODS:
      According to the Cochrane systemic analysis method, randomized controlled trials
      and quasi-randomized controlled trials which were about the comparison of PFNA
      and InterTAN for intertrochanteric fracture were collected from Cochrane
      Library(2017, issue 4), PubMed (January, 2003-May, 2017), Wanfang Med Online
      (January, 2003-May, 2017) and China Academic Journals Full-text Database(January,
      2003-May, 2017) by computer searching. Cross-checking was done after assessing
      the quality of the included trials and extracting the data by two reviewers
      independently. Data analysis were performed with RevMan 5.3. RESULTS: Two
      randomized controlled trials and five quasi-randomized controlled trials
      involving 611 cases met the inclusion criteria. The meta-analyses showed no
      significant differences between the two methods on Harris scores[MD=-1.00, 95%CI(
      2.29, 0.28), P=0.13], union time[MD=0.04, 95%CI (-0.70, 0.77), P=0.92], full
      weight-bearing time[MD=1.06, 95%CI(-0.29, 2.42), P=0.13], hospital stay[MD=-0.04,
      95%CI (-0.52, 0.45), P=0.89] and length of incision[MD=-1.00, 95%CI (-2.64,
      0.65), P=0.23]. There were significant differences between the two methods on
      operative time[MD=-25.75, 95%CI (-37.47, -14.03), P<0.000 1], intraoperative
      blood loss[MD=-55.67, 95%CI(-108.07, -3.27), P=0.04] and the internal fixation
      complication rate[MD=4.17, 95%CI (1.33, 13.08), P=0.01]. CONCLUSIONS: Both PFNA
      and InterTAN could provide good effect for intertrochanteric fracture. The
      operation time of PFNA is shorter than that of InterTAN, and there is less blood
      loss during operation. PFNA may be the first choice for the treatment of patients
      who have many complications and can't endure long-time operation. The
      complications of PFNA are more than those of InterTAN. In patients with long life
      expectancy and high requirements, InterTAN may be preferentially selected to
      reduce complications. According to the patient's situation, after a comprehensive
      consideration, appropriate treatment can be selected.

PMID- 29457417
TI  - [Clinical observation of the second operation for refracture after internal
      fixation of clavicle].
AB  - OBJECTIVE: To evaluate the outcome of Titanium Elastic intramedullary
      nailing(TEN) for the treatment of refracture of clavicle. METHODS: From March
      2010 to March 2016, 9 cases of clavicle fracture, postoperative re-fracture
      (plate broken before fracture healing, plate and screw pull out or refracture
      after fracture union and internal fixation removal) included 6 males and 3
      females with a mean age of 38.6 years old ranging from 20 to 62 years old; 3
      cases were sports injury, 5 cases were traffic injury, 1 case was severe injury.
      All cases were closed fractures, and 2 cases were multiple fractures. According
      to OTA(Orthopaedic Trauma Association classification), 2 cases were 06-A1, 1 case
      was 06-A2, 1 case was 06-A3, 2 cases were 06-B1, 2 cases were 06-B2, and 1 case
      was 06-B3. Among them, 4 cases were treated with AO titanium elastic
      intramedullary nail (TEN), and 5 cases of early internal fixation failure of
      clavicle fracture were treated with plate and screw internal fixation plus bone
      graft. The time of bone union, VAS score and Constant Shoulder Score were
      observed and recorded. RESULTS: All incisions healed at stage I without
      infection. All 9 patients were followed up for a period of 14 months. All
      patients' implants were removed at 12 months after the second operation without
      refractures. The Constant score of shoulder joint was from 64 to 94 at 4 weeks
      after the second operation, 91 to 100 at 4 weeks after implants removal. The
      average bone healing time was 4.3 months from 3 to 6 months. The pain VAS score
      decreased significantly and the pain was relieved significantly. CONCLUSIONS:
      Titanium elastic intramedullary nail (TEN) for the treatment of clavicle fracture
      after internal fixation of refracture patients can be achieved better outcomes,
      less trauma, good fracture healing, good postoperative recovery of shoulder joint
      function, but need to pay attention to the reasonable selection of patients.

PMID- 29457418
TI  - [Outcomes and complications of Tightrope button plate for repairing
      acromioclavicular dislocation].
AB  - OBJECTIVE: To study the clinical outcome and complications of Tightrope button
      plate for repairing acromioclavicular dislocation of Rockwood type III to V.
      METHODS: From May 2014 to December 2016, 17 patients with acromioclavicular
      dislocation of type III-V were treated with Tightrope button plate including 10
      males and 7 females with an average age 39.8 years old ranging from 20 to 68
      years old. Four patients were treated with arthroscopy and 17 patients were
      treated with mini-invasive by X-ray assisted. Shoulder function, X-ray and
      complications after operation were assessed. RESULTS: All patients were followed
      up for 5 to 23 months with a mean of 10.8 months. All patients got satisfying
      reduction immediately postoperatively. Among them, 1 case of clavicle end wound
      foreign body reaction, rupture, effusion, healing after the second suture; 1 case
      of foreign body granuloma formation at the end of clavicle were resected and
      removed at 4 months after operation; 3 cases loss reduction(less than 50% of
      acromioclavicular joint). No coracoid fracture and suture breakage observed. The
      shoulder mobility was restored in 15 cases at 4 to 6 weeks postoperatively, and
      the shoulder adhesion in 2 cases was delayed to 5 to 7 months after operation.
      The Constant scores were improved from 46.9+/-6.0 preoperatively to 92.7+/-4.0 at
      the final follow-up. X-ray evaluation of postoperative coracoclavicular tunnel
      location, patients' coracoclavicular tunnel with mini-invasive fluoroscopy all
      closed to the ideal position (across the clavicle vertically through the coracoid
      base center), while different degree of tunnel position deviation were observed
      in arthroscopic patients. CONCLUSIONS: Tightrope button plate for the treatment
      of acromioclavicular joint dislocation had advantages of minimally invasive,
      effective, good clinical results, the majority of common complications does not
      affect efficacy. Small incision X-ray method can provide more satisfactory and
      reliable tunnel location.

PMID- 29457419
TI  - [Treatment of scapular fractures with lateral incision and bridge combined
      internal fixation system].
AB  - OBJECTIVE: To investigate the clinical results of scapula fractures with lateral
      incision combined with bridge internal fixation system. METHODS: From October
      2012 to December 2016, 20 cases of scapular fractures were treated through the
      lateral incision combined with bridge fixation system, including 15 males and 5
      females, with an average age of 31.6 years old(ranged, 21 to 52 years old).
      Fourteen cases were scapular body fracture, 10 were scapular neck fracture, 6
      were scapular fracture, 1 was acromion fracture, 1 was coracoid fracture, 4 were
      the glenoid rim fracture, 3 were the glenoid fossa fracture. The operation time
      ranged from 4 to 15 d after injury with an average of 10 d. RESULTS: All 20 cases
      were followed up for 3 to 24 months with an average of 15 months. Wound infection
      occurred in 2 cases after operation, and was healed after wound debridement and
      change dressing; no osteomyelitis, iatrogenic nerve injury, breakage of internal
      fixation, fracture displacement, joint stiffness occurred. Callus growth was
      observed at the fracture site 3 months after operation, the fracture healing time
      was 4 to 7 months, fracture healing was good without delayed union or malunion.
      According to Hardegger shoulder score, the results were excellent in 12 cases,
      good in 6 cases, moderate in 2 cases. CONCLUSIONS: Lateral incision approach
      combined with bridge internal fixation system for scapula fractures has the
      advantages of easy operation, revealed clearly, and the incision can be arbitrary
      to extend on both sides, to provide favorable conditions for the reduction and
      fixation of fracture. Bridge combined internal fixation system has the advantages
      of flexible operation, reliable fixation strength, is a good choice for treatment
      of scapula fracture.

PMID- 29457420
TI  - [Treatment of intercondylar fracture of the humerus through internal and external
      elbow approach or elbow posterior olecranon osteotomy approach].
AB  - OBJECTIVE: To investigate the efficacy, advantages and disadvantages of internal
      and external elbow joint approach and olecranon osteotomy approach for the
      treatment of intercondylar fracture of humerus. METHODS: From October 2012 to May
      2016, 18 cases of intercondylar fracture of humerus were treated by operation
      including 12 males and 6 females with a mean age of 33.5 years old (ranged from 4
      to 56 years old); 8 cases were operated by internal and external elbow joint
      approach, 10 cases were operated by olecranon osteotomy approach. According to AO
      classification, 3 cases were type C1, 8 cases were type C2, 7 cases were type C3.
      All patients were excluded from neurologic and vascular injuries. RESULTS: All
      patients were followed up from 12 to 26 months with an average of 15 months. The
      incision healed well and no heterotopic ossification was found. According to the
      modified Cassebaum elbow function score, the result was excellence in 14 cases,
      good in 3 cases, fair in 1 case. CONCLUSIONS: According to the fracture type, the
      appropriate surgical approach and fixation were selected in order to get anatomic
      reduction. Rigid fixation, and early functional exercise is important condition
      for successful operation and satisfactory functional recovery in intercondylar
      fracture of the humerus.

PMID- 29457421
TI  - [Minimally invasive elastic intramedullary nailing for the treatment of radial
      neck fracture in children: a report of 18 cases].
AB  - OBJECTIVE: To investigate effects of elastic stable intramedullary nails(ESIN)
      for the treatment of radial neck fracture in children. METHODS: From January 2014
      to April 2017, 18 children with radial neck fractures were treated with minimally
      invasive internal fixation including 6 males and 12 females with an average age
      of 8.6 years old ranging from 4 to 15 years old; 7 cases were on the left, 11
      cases on the right. According to Judet type, 5 cases were type II, 9 cases were
      type III, 1 case was type IVa, 3 cases were type IVb. Postoperative radial neck
      fracture healing, elbow pain, deformity and range of activities were recorded.
      RESULTS: All children were followed up for 3 to 14 months with an average of 8
      months. All fractures were healed well. There was 1 case of nail tail irritation,
      and the fracture healed and pain disappeared after removal. Satisfactory results
      were achieved in 1 case after reduction and fixation, but a lateral and
      angulation shift in 20 degrees was observed after 2 days, while the elbow joint
      function seen well at 6 months. According to Tibone-Stoltz clinical function
      assessment criteria, the results were excellent in 11 cases, good in 5 cases,
      fair in 2 cases. CONCLUSIONS: The operation of elastic intramedullary nail
      fixation for the treatment of radial neck fracture in children is simple,
      reliable and minimally invasive, which can restore functional activity and less
      complication as soon as possible.

PMID- 29457422
TI  - [A case report of Madelung's deformity and literature review].

PMID- 29457423
TI  - [Tumor-induced osteomalacia: a case report].

PMID- 29457424
TI  - [Progress on diagnosis and treatment of proximal tibiofibular joint dislocation].
AB  - Dislocation of proximal tibiofibular joint(PTFJ) is relatively infrequent in
      clinic, it can be either isolated or associated with tibia fracture, fibular
      fracture and ankle injury and so on. Chronic symptomatic PTFJ instability are
      easily mixed with meniscal tears. It was easily neglected because of the mild
      clinical presentation and atypical change on radiography. Early diagnosis and
      treatment are crucial to prevent chronic knee pain and instability. The paper
      concluded the anatomy, classification, complication, diagnosis, treatment,
      clinical effect and insufficient of the dislocation of PTFJ, to direct the
      diagnosis and treatment of proximal tibiofibular joint dislocation in clinical
      work.

PMID- 29457425
TI  - [Progress on research of Madelung's deformity].
AB  - Madelung deformity is a rare deformity of forearm and wrist caused by growth
      disorders of distal radius ulnar and palmar epiphyseal. Current studies showed
      that its incidence mainly associated with trauma, epiphyseal developmental
      abnormalities, nutritional disorders and genetic deletion or mutation. The early
      clinical presentation is not typical, in middle and late time, wrist deformity
      and weak can appear. Plain film considered as the main means of diagnosis is
      often lack of early diagnosis significance. Although wrist joint magnetic
      resonance imaging showing early soft tissue and skeletal abnormalities were used
      for the early diagnosis of the disease, current domestic study in magnetic
      resonance imaging of this deformity is less. According to the size of the distal
      ulnar inclination angle and palm angle, this deformity can be divided into
      different types. The patients with severe deformity and symptoms usually need
      surgical intervention including ulna revision and osteotomy of the distal radius
      at present. Although the two operation can achieve good clinical results, the
      surgical trauma, infection and postoperative risk of joint activities are more.

PMID- 29457426
TI  - [Progress on treatment for calcaneal fracture].

PMID- 29457427
TI  - [Percutaneous reduction and Kirschner pin flxation through sinus tarsi approach
      for the treatment of Sanders type III calcaneal fracture].
AB  - OBJECTIVE: To investigate clinical effect of percutaneous reduction and Kirschner
      pin flxation through sinus tarsi approach in treating Sanders type III calcaneal
      fracture. METHODS: Totally 22 patients (22 feet) with Sanders III calcaneal
      fracture were treated with percutaneous reduction and Kirschner pin flxation
      through sinus tarsi approach form September 2013 to December 2015. Among them,
      including 18 males and 4 females; aged from 20 to 65 years old with an average of
      (41.73+/-12.46) years old. Bohler angle, Gissane angle and calcaneal width before
      and after operation were observed and compared, Maryland scoring system was used
      to evaluate curative effect; postoperative complications were recorded. RESULTS:
      All patients were followed up from 18 to 36 months with an average of (27.05+/
      4.92) months. All fractures healed well with an average of (10.73+/-1.24) weeks.
      Bohler angle before operation (11.36+/-5.92) improved to (33.36+/-3.99) after
      operation, and had significant differences(P<0.05); there was significant
      difference of Gissane angle between preoperation (99.23+/-8.61) and postoperation
      (114.64+/-6.93); calcaneal width was improved from (46.59+/-1.40) mm before
      operation to (42.15+/-0.75) mm at 3 months after operation (P<0.05). Maryland
      score was (95.05+/-6.86) points, 16 patients obtained excellent results, 5
      patients moderate, and 1 patient poor. No inflammation, flap margin necrosis and
      osteomyelitis occurred. CONCLUSIONS: Compared with conventional internal fixation
      through L-shape incision, percutaneous reduction and Kirschner pin flxation
      through sinus tarsi approach in treating Sanders type III calcaneal fracture
      obtained satisfied clinical effects, and has advantages of invasive trauma,
      simple operation, easy to remove and less complication. Meanwhile, careful
      operation and identification should be done during sinus tarsi approach operation
      to protect sural nerve and tendon.

PMID- 29457428
TI  - [Percutaneous poking reduction with bone grafting and limited internal fixation
      for the treatment of calcaneal fractures].
AB  - OBJECTIVE: To investigate clinical effects of percutaneous poking reduction with
      bone grafting and limited internal fixation for the treatment of calcaneal
      fractures. METHODS: From May 2013 to October 2016, 53 patients with closed
      calcaneal fractures were analyzed, and were divided into treatment group and
      control group. There were 33 patients in treatment group including 25 males and 8
      females, aged from 15 to 82 years old with an average of(44.7+/-14.2) years old;
      17 cases were type II and 16 cases were type III according to Sanders
      classification; treated by percutaneous poking reduction with bone grafting and
      limited internal fixation. There were 33 patients in control group, including 20
      males aged from 25 to 62 years old with an average of (42.2+/-11.3) years old; 8
      cases were type II and 12 cases were type III according to Sanders
      classification; treated by open reduction and internal fixation. Imaging
      indicators, hospital stays and preoperative waiting time were observed and
      compared, Maryland scoring were applied to evaluate foot function. RESULTS: Fifty
      three patients were followed up, and treatment group was followed up from 8 to 40
      months with an average of (19.9+/-7.2) months; while control group was followed
      up from 12 to 40 months with an average of (21.7+/-7.7) months, and there were
      not significant differences between two groups in follow-up time (P>0.05). There
      were no obvious meaning in Bohler angles, Gissane angles between two groups
      (P>0.05). There were significant differences in hospital stays and preoperative
      waiting time(P<0.01). There were no significant differences in Maryland score
      between treatment group(90.45+/-5.76) and control group(89.10+/-6.16).
      CONCLUSIONS: Percutaneous poking reduction with bone grafting and limited
      internal fixation for the treatment of calcaneal fractures could obtain satisfied
      effects, and has advantages of less trauma and complications, rapid recovery and
      good clinical effects.

PMID- 29457429
TI  - [Stiletto needle and needle-knife for influence of gravity index in treating knee
      osteoarthritis].
AB  - OBJECTIVE: To explore stiletto needle and needle-knife for influence of double
      sufficient weight in treating knee osteoarthritis patients. METHODS: One hundred
      and thirteen early and medium term knee osteoarthritis patients were randomly
      divided into three groups, including stiletto needle group(38 cases), needle
      knife group (38 cases) and voltaren group (37 cases). In stiletto needle group,
      there were 13 males and 25 females with an average of(55.87+/-7.72) years old,
      treated by stiletto needle once a week, and 2 weeks were a course; there were 11
      males and 27 females in needle-knife group with an average of(57.11+/-7.07) years
      old, treated by acupotome once a week, and 2 weeks were a course; there were 12
      males and 25 females in voltaren group with an average age of(57.62+/-8.08) years
      old, treated by votalin emulsion smearing 3 to 5 cm on painful area of knee
      joint, three times a day for 2 weeks; 36 patients in normal group, including 11
      males and 25 females with a mean age of (55.28+/-7.55) years old, treated with
      nothing. Gravitational four lattice used to measure bipedal back and forth load
      before and after treatment in further observe weight-bearing situation among
      three groups, d value, which was the distance from center of gravity to original
      point, was measured as a obvervational index, JOA score was used to evaluate
      clinical effect. RESULTS: Five patients were fall out, including 2 patients in
      stiletto needle group, 2 patients in needle-knife group and 1 patient in voltaren
      group. Other 108 patients were followed-up from 28 to 35 d with an average of 30
      d, and without untoward effect. There was significant difference in d value
      between treatment group and control group at 1 month after treatment(P<0.05);
      there was significant difference in d value among treatment group at 1 month
      after treatment(P>0.05), and d value was decreased before treatment than that of
      after treatment. There was no significant difference in JOA score among treatment
      group after treatment at 1 month(P<0.05); while had significant difference
      between groups(P>0.05) after treatment at 1 month. CONCLUSIONS: Stiletto needle,
      needle-knife and voltaren for the treatment of knee osteoarthritis at early and
      middle stage, center of gravity is closer to original point, and weight-bearing
      is improved. It is a easy method of four lattice to measure change of weight
      bearing in KOA patients after treatment.

PMID- 29457430
TI  - [Clinical effect of superselective arterial embolization for the treatment of
      massive haemorrhage from pelvic fracture].
AB  - OBJECTIVE: To investigate feasibility and curative effect of superselective
      arterial embolization for the treatment of massive haemorrhage from pelvic
      fracture. METHODS: From March 2008 to February 2016, clinical data of 65 patients
      with massive haemorrhage from pelvic fracture were collected and analyzed, and
      patients were divided into non-embolic and embolic group according to whether
      perform vascular thrombosis. Thirty-three patients were in non-embolic group
      including 26 males and 7 females aged from 21 to 64 years old with an average
      of(39.2+/-5.7) years old, the time from injury to operation ranged from 1.1 to
      4.8 h with an average of (2.2+/-0.4) h; 12 cases were type B and 21 cases were
      type C according to AO/Tile classification; injury severity score (ISS) ranged
      from 25 to 42 with an average of (37.7+/-7.5); shock index score ranged from 1.7
      to 2.4 with an average of 2.1+/-0.3; treated with blood transfusion and fluid
      infusion. Thirty-two patients in embolic group, including 25 males and 7 females
      aged from 22 to 65 years old with an average of(38.1+/-4.5) years old; the time
      from injury to operation ranged from 1.2 to 4.8 h with an average of (2.1+/- 0.5)
      h; 14 cases were type B and 18 cases were type C according to AO/Tile
      classification; ISS ranged from 26 to 43 with an average of 38.9+/-4.5; shock
      index score ranged from 1.6 to 2.4 with an average of 2.2+/-0.2; treated by blood
      transfusion and fluid infusion with superselective arterial embolization. Blood
      transfusion volume, fluid infusion volume, shock correction time and survival
      rate were observed and compared, effective rate of hemostasis and postoperative
      complications were compared. RESULTS: Thirty-seven artery were injured in embolic
      group, hemostasis were controlled at 3 h after operation, and hemodynamics turned
      to stable. There were significant difference in blood transfusion volume, fluid
      infusion volume, shock correction time between non-embolic and embolic group, and
      embolic group performed better. Survival rate in embolic group was also better
      than that of non-embolic group, and had significant difference. While there was
      obvious differences in complications(chi2=4.03, P=0.045). CONCLUSIONS:
      Superselective arterial embolization for massive haemorrhage from pelvic fracture
      could effective hemostasis, reduce blood transfusion and fluid infusion volume
      and occurrence rate of shock, moreover improve survival rate and deserves
      promotion.

PMID- 29457431
TI  - [Efficacy analysis on hip replacement for hip-joint diseases with Parkinson
      disease].
AB  - OBJECTIVE: To explore clinical efficacy of hip replacement for hip-joint diseases
      with Parkinson disease. METHODS: From December 2011 to December 2016, 18 patients
      with hip-joint diseases with Parkinson disease treated by hip replacement,
      including 8 males and 10 females aged from 59 to 87 years old with an average of
      71 years old. Among them, 3 cases were developmental dysplasia of hip, 3 cases
      were femoral head necrosis and 12 cases were femoral neck fracture. All patients
      manifested with obvious pain and limitation of stepping ability. Postoperative
      complications were observed and Harris score were used to compare hip joint
      function after operation. RESULTS: The incision were healed well, and pain were
      alleviated or disappeared, and hip joint function were improved. Eighteen
      patients were followed up from 1 to 3 years with an average of 2.3 years. At the
      latest follow up, 14 cases recovered freedom-walk, 2 cases could walk with
      walking stick, 1 case could walk with walking aid and 1 case was died. Among 18
      patients, 2 cases were occurred dislocation, and 1 case were died for cardiac
      disease at 3 months after operation. Four patients were occurred slight pain.
      There were significant differences in Harris scores among preoperative (41.7+/
      1.4), 6 months after operation(80.1+/-5.4) and the final follow-up (83.4+/-2.1),
      and 10 cases got excellent result, 4 good, 1 fair and 2 poor. CONCLUSIONS:
      Application of hip replacement for hip-joint diseases with Parkinson disease is a
      safe and effective clinical therapy, and has advantages of less complications and
      rapid recovery of hip joint function.

PMID- 29457432
TI  - [Micro-CT evaluating inhibitory effect of zoledronic acid on polyethylene
      particle-induced periprosthetic osteolysis model].
AB  - OBJECTIVE: To observe inhibitory effect of zoledronic acid on polyethylene
      particle-induced periprosthetic osteolysis model. METHODS: Thirty male adult
      specific-pathogen-free SD rats (weighted 250 to 300 g) were randomly divided into
      sham group, model group, and zoledronic acid group, 10 in each group. Modeling
      were building by titanium screws and polyethylene particles implanted into right
      femur of rats, sham group and model group were performed hypodermic injection by
      0.9% saline with 2 ml/kg, zoledronic acid with 0.1 ml/mg were injected into
      zoledronic acid group, once a week for 8 weeks. After 8 weeks, right femur
      specimens were drawn and used to san microstructure of femoral cancellous bone in
      rats model was examined by Micro-CT, and the images were treated with three
      dimension reconstruction and analysis software BMD, BV/TV, Tb.N, Tb.Th, SMI,
      BS/BV, Tb.Sp and Tb.Pf and other parameters include. RESULTS: According to Micro
      CT three-dimensional imaging, BMD in model group was significantly decreased than
      sham group, bone microstructure damage was serious, bone trabecula changed
      thinning continuity; while bone microstructure was obviously improved compared
      with model group and zoledronic acid group. After analyzing Micro-CT parameters
      of femur microstructure, BMD in model group(0.081+/-0.020) was significantly
      decreased than control group(0.160+/-0.018) and zoledronic acid group(0.125+/
      0.012); BV/TV in model group (10.563+/-1.070) was obviously lower than control
      group(27.935+/-1.834) and zoledronic acid group(14.559+/-1.258); Tb.N in model
      group (1.005+/-0.165) was lower than control group(2.058+/-0.108) and zoledronic
      acid group(1.515+/-0.126); while Tb.Th in model group (0.075+/-0.016) was
      decreased than control group(0.158+/-0.016) and zoledronic acid group(0.124+/
      0.011). Meanwhile, SMI in model group(1.817+/-0.127) was significantly higher
      than control group(1.104+/-0.120) and zoledronic acid group(1.547+/-0.122); BS/BV
      in model group(35.784+/-1.650) was higher than control group(21.506+/-2.771) and
      zoledronic acid group(30.399+/-2.730); Tb.Sp in model group(0.735+/-0.107) was
      higher than control group(0.423+/-0.057) and zoledronic acid group(0.577+/
      0.082), TB.Pf in model group(9.088+/-1.283) was higher than control group(2.447+/
      0.703) and zoledronic acid group(5.862+/-1.042). CONCLUSIONS: Zoledronic acid
      could change bone microstructure of rats to inhibit polyethylene particle-induced
      bone solution, which provides a scientific basis for prevent bone solution by
      zoledronic acid as a therapeutic intervention.

PMID- 29457433
TI  - [Effect of 50 Hz 1.8 mT sinusoidal electromagnetic fields on bone mineral density
      in growing rats].
AB  - OBJECTIVE: To study effects of 50 Hz 1.8 mT sinusoidal electromagnetic fields
      (SEMFs) on bone mineral density (BMD) in SD rats. METHODS: Thirty SD rats
      weighted(110+/-10) and aged 1 month were randomly divided into control group and
      electromagnetic field group, 15 in each group. Normal control group of 50 Hz 0 mT
      density and sinusoidal electromagnetic field group of 50 Hz 1.8 mT were performed
      respectively with 1.5 h/d and weighted weight once a week, and observed food
      intake. Rats were anesthesia by intraperitoneal injection and dual energy X-ray
      absorptiometry were used to detect bone density of whole body, and detected bone
      density of femur and vertebral body. Osteocalcin and tartrate-resistant acid
      phosphatase 5b were detected by ELSA; weighted liver, kidney and uterus to
      calculate purtenance index, then detected pathologic results by HE. RESULTS:
      Compared with control group, there was no significant change in weight every
      week, food-intake every day; no obvious change of bone density of whole body at 2
      and 4 weeks, however bone density of whole body, bone density of excised femur
      and vertebra were increased at 6 weeks. Expression of OC was increased, and TRACP
      5b expression was decreased. No change of HE has been observed in liver, kidney
      and uterus and organic index. CONCLUSIONS: 50 Hz 1.8 mT sinusoidal
      electromagnetic fields could improve bone formation to decrease relevant factors
      of bone absorbs, to improve peak bone density of young rats, in further provide a
      basis for clinical research electromagnetic fields preventing osteoporosis
      foundation.

PMID- 29457434
TI  - [Minimally invasive sinus tarsal approach versus conventional L-shaped lateral
      approach in treating calcaneal fractures: a Meta-analysis].
AB  - OBJECTIVE: To compare efficacy and safety of minimally invasive sinus tarsal
      approach versus conventional L-shaped lateral approach in treating calcaneal
      fractures. METHODS: The studies concerning about randomized controlled trial and
      non-randomized controlled trial of minimally invasive sinus tarsal approach
      versus conventional L-shaped lateral approach in treating calcaneal fractures
      from the time of creating database to March, 2017 were searched from PubMed,
      Cochrane Central Register of Controlled Trials (CENTRAL), EMbase, ISI Web of
      Knowledge databases, VIP, CNKI, CBM and Wan Fang. The literatures which screened
      by randomized controlled trial and non- randomized controlled trial were
      extracted and performed quality assessment by two people. Meta analysis were
      performed by RevMan 5.3 software and GRADE system were used to evaluate quality.
      RESULTS: Four randomized controlled trial and 4 non-randomized controlled trial
      were included, totally 493 patients. Meta-analysis results showed compared with
      conventional L-shaped lateral approach, minimally invasive sinus tarsal approach
      had shorter operative time [MD=-5.41, 95%CI(-6.71, -4.12), P<0.000 01], lower
      incidence of postoperative complications[OR=0.10, 95%CI(0.05, 0.21), P<0.000 01],
      and higher AOFAS score [MD=-3.09, 95%CI(-1.72, 4.46), P<0.000 01] at the final
      follow-up. Bohler angle in conventional L-shaped lateral approach was better than
      that of minimally invasive sinus tarsal approach [MD=-0.80, 95%CI(-1.45, -0.14),
      P<0.05]. While there were no significant differences in postoperative Gissanes
      angle [MD=0.35, 95%CI(-0.77, 1.47), P>0.05] and Maryland score[MD=2.12, 95%CI(
      0.71, 4.95), P>0.05] between two groups. CONCLUSIONS: Minimally invasive sinus
      tarsal approach and conventional L-shaped lateral approach has similar clinical
      effect for the treatment of calcaneal fractures. However, minimally invasive
      sinus tarsal approach has advantages of shorter operation time, lower incidence
      of complication and better safety. For the limited quantity of the original
      studies, operative approach should be chosen according to the patient.

PMID- 29457435
TI  - [Repair soft-tissue defect in forefoot with reversed lateral soleus muscle flap].
AB  - OBJECTIVE: To summarize clinical application results of repair soft tissue defect
      in forefoot with a reversed lateral soleus muscle flap on peroneal artery
      pedicle. METHODS: From January 2005 to January 2013, 8 patients with soft-tissue
      defect on forefoot were underwent reconstruction with a reversed lateral soleus
      muscle flap on peroneal artery pedicle. There were 6 males and 2 female, aged
      from 16 to 48 years with an average of 26.8 years old. The reversed lateral
      soleus muscle flap was transposed to the forefoot defect area, then immediate
      coverage of the muscle flaps were performed by a meshed split-thickness free skin
      graft. The donor site was closed directly. The muscle flap survey was observed
      after the repair of the forefoot. RESULTS: All muscle flaps had survived
      completely. No clinical vascular deficiency was found on muscle flaps
      postoperatively. One case occurred recipient area sustained insignificant
      superficial infection, one patient developed distal muscle flap small skin graft
      necrosis, and spontaneous heal by 2 weeks' change dressing. Follow-up period was
      ranged form 2.5 to 5.5 years with an average of 3.5 years postoperatively. A good
      contour was confirmed at the recipient area. According to Cedell questionnaire, 6
      patients obtained good results and 2 fair. CONCLUSIONS: When the local skin flap
      or muscle flap application is limited, lateral soleus muscle flap survey is
      satisfactory after repair and very suitable for repair of soft tissue defect of
      forefoot.

PMID- 29457436
TI  - [Clinical application of tibial composite saphenous nervetissue flap for the
      treatment of traumatic bone-skin defect of leg].
AB  - OBJECTIVE: To investigate the effect of tibial composite saphenous nerve tissue
      flap in repairing traumatic bone-skin defect of leg. METHODS: From February 2009
      to May 2015, 23 patients with focile skin defect caused by trauma were treated,
      including 18 males and 5 females, aged from 8 to 59 years old with an average age
      of 35.6 years old. Length of tibia bone cortex defect ranged from 4 to 12 cm,
      width ranged from 2 to 2.5cm, skin defect ranged from 8 cm* 3 cm to 18 cm* 11 cm,
      all the wound surfaces had purulent exudation. Cross shift and ipsilateral shift
      methods of tibial composite saphenous nerve tissue flap were used to reconstruct
      continuity of the injured limb tibial brace and repair wound surface. Cutting
      flap ranged from 9 cm* 4 cm to 20 cm * 12 cm, bone flap length was 6 to 15 cm,
      width was 1.5 to 2.5 cm. Fracture healing time and recovery of limb function were
      observed. RESULTS: At 3 to 5 months after operation, bone flap and area of
      affected area were healed with an average of 4.7 months. Twenty-three cases were
      followed up for 6 months to 5 years with an average of 30.3 months. Thirteen
      patients were able to walk without abnormal gait and could be engaged into
      original work. According to Enneking evaluation systems, 13 patients obtained
      excellent results, 8 moderate and 2 poor. CONCLUSIONS: With tibial composite
      saphenous nerve tissue flap transplantation at stage one to repair tibia and skin
      defects according to specific condition of affected limbs has a high rate of
      success and creates less damage to region of limb injury, which is an ideal
      method to repair skin defect of focile.

PMID- 29457437
TI  - [Clinical application value of MRI on malignant fibrous histiocytoma in soft
      tissue].
AB  - OBJECTIVE: To investigate imaging manifestation and clinical application of MRI
      on malignant fibrous histiocytoma (MFH) in soft tissue. METHODS: Imaging and
      pathological data of 16 patients with malignant fibrous histiocytoma (MFH) in
      soft tissue confirmed by surgery and pathology were retrospectively analyzed from
      January 2009 to August 2016. There were 9 males and 7 females, aged from 34 to 67
      years old with an average of 52 years. The courses of disease ranged from 5 to 48
      months with an average of 27 months.The main clinical manifestations were soft
      tissue mass and local pain. All patients were underwent plain and enhanced MRI
      before operation. Pathogenic sites, MRI manifestation and pathology results were
      observed after operation. RESULTS: MRI in 16 cases of T1WI showde slightly lower
      signal or equal signals, of which 6 cases of tumor see mixed signal; in T2WI were
      high signal, of which 7 cases of internal tumor can be seen low signal
      separation, 5 cases of turor can be seen flase envelope, 11 cases of tumor with
      the surrounding boundaries unclear with edema. All lesions showed significantly
      uneven enhancement. Immunohistochemical examination showed that Vim, CD68 was
      positive. CONCLUSIONS: Although MRI features of MFH has certain characteristics,
      the qualitative was more difficult, and ultimately need to determine the
      pathological and immunohistochemical. But MRI examination has obvious advantages
      in clarifying range of tumor, invading peripheral blood vessels and nerves, and
      has important clinical application value for clinical operation plan and
      postoperative tumor residual and recurrence, and provid reference for clinical
      curative effect.

PMID- 29457438
TI  - [CT and MRI manifestation of primary spinal large B cell lymphoma].
AB  - OBJECTIVE: To investigate CT and MRI characteristics of primary spinal large B
      cell lymphoma. METHODS: CT and MRI data of 23 patients with primary spinal large
      B cell lymphoma confirmed by histopathology were retrospectively analyzed from
      March 2011 to August 2015. Among them, including 14 males and 9 females aged from
      28 to 70 years old with an average of 53.4 years old. The clinical manifestation
      mainly focus on pain around spinal and minority peripheral nerve symptom. The
      courses of disease ranged from 2 weeks to 3 months with an average of 9 weeks.
      Nine patients underwent CT plain scan, 8 patients underwent plain and enhanced
      CT; 21 patients underwent MRI plain scan and enhanced; 15 patients underwent CT
      and MRI examination. The location, bone changes, shape, density, signal intensity
      and enhancement characteristics of lesions were observed and compared with
      pathology. RESULTS: Location and size of lesion showed cervical vertebrae in 1
      case, thoracic vertebrae in 16 cases, lumbar vertebrae in 2 cases, and sacral
      vertebrae in 4 cases. Mass was larger, the largest cross-sectional size of group
      was up to 73 mm* 125 mm. CT examination showed that 11 cases with "cloud and
      mist" shape change, 6 cases with compression fractures, and with "floating ice"
      shape change, 9 cases with "oversleeve" shape change, 11 cases with spinal
      stenosis; enhancement scan showed obvious reinforcement. MRI showed slightly low
      signal on T1WI and T2WI were slightly high signal, and signal was uneven, and
      enhancement scan showed obvious reinforcement, 13 of 16 cases with spinal canal
      stenosis changed like "oversleeve", intervertebral space showed no significant
      stenosis. Comparison of CT and MRI showed the manifestation of bone destruction
      by CT was superior than that of MRI, but the range of lesion, and related
      surrounding structures were not better than MRI. MRI displayed the range of
      lesion usually bigger than CT. Pathology results showed that 23 patients were all
      primary spinal large B cell lymphoma. CONCLUSIONS: Primary spinal large B cell
      lymphoma has certain features in age, location and imaging findings. The "cloud
      and mist", "floating ice" and "oversleeve" shape bony destruction by CT and MRI
      has certain significance to diagnosis of primary spinal large B cell lymphoma.

PMID- 29457440
TI  - [A case report of Brucellosis spondylitis with epidural abscess].

PMID- 29457439
TI  - [Antero-medial incision of knee joint for the treatment of intercondylar fracture
      of femur].
AB  - OBJECTIVE: To explore the clinical effect of antero-medial incision of knee joint
      in treating intercondylar fracture of femur. METHODS: From September 2012 to
      March 2015, 24 patients with intercondylar fracture of femur were selected,
      including 17 males and 7 females, aged from 20 to 65 years old with an average
      of(38.3+/-9.5) years old. Among them, 12 cases were caused by traffic accident, 8
      cases were caused by falling injury and 4 cases were caused by falling down. All
      patients were closed fractures. The time from injury to hospital was from 30 min
      to 8 h with an average of(2.2+/-0.3) h. According to AO classification, 4 cases
      were type B1, 3 type B2, 2 type B3, 5 type C1, 6 type C2 and 4 type C3. All
      patients were treated with antero-medial incision of knee joint. Operative time,
      blood loss and postoperative complications were observed and recovery of keen
      function was evaluated by Kolmert scoring. RESULTS: All patients were followed-up
      from 6 to 12 months with average of (9.0+/-1.7) months. Operative time ranged
      from 50 to 90 min with an average of (70.0+/-8.2) min; blood loss ranged from 90
      to 400 ml with an average of (180+/-36) ml; negative pressure flow was from 30 to
      90 ml, with an average of (50.0+/-7.1) ml. All fracture were healed at stage I
      without loosening of internal fixator, fracture nonunion, and deep vein
      thrombosis. According to Kolmert scoring, 16 patients got excellent result, 5
      patients good and 3 fair. CONCLUSIONS: Antero-medial incision of knee joint in
      treating intercondylar fracture of femur, which has advantages of good fracture
      reduction, less injury of soft tissue and simple operation, could obtain good
      clinical results.

PMID- 29457441
TI  - [A case report of aged radius plasticity bend].

PMID- 29457442
TI  - [Development and application of artificial vertebral body].
AB  - Artificial vertebral body has achieved good results in treating spinal tumors,
      tuberculosis, fracture and other diseases. Currently, artificial vertebral body
      with variety of kinds and pros and cons, is generally divided into two types:
      fusion type and movable type. The former according to whether the height could be
      adjusted and strength of self-stability is divided into three types: support
      fixed type, adjust-fixed type and self-fixed type. Whether the height of self
      fixed type could be adjusted is dependent on structure of collar thread rotation.
      The latter is due to mobile device of ball-and-socket joints or hollow structures
      instead of the disc which retains the activity of the spine to some extent.
      Materials of artificial vertebral body include metals, ceramics, biomaterials,
      polymer composites and other materials. Titanium with a dominant role in the
      metal has developed to the third generation, but there are still defects such as
      poor surface bioactivity; ceramics with the representative of hydroxyapatite
      composite, magnetic bioceramics, polycrystalline alumina ceramics and so on,
      which have the defects of processing complex and uneven mechanical properties;
      biological material is mainly dominated by xenogeneic bone, which is closest to
      human bone in structure and properties, but has defects of low toughness and
      complex production; polymer composites according to biological characteristics in
      general consists of biodegradable type and non-biodegradable type which are
      respectively represented by poly-lactide and polyethylene, each with advantages
      and disadvantages. Although the design and materials of prosthesis have made
      great progress, it is difficult to fully meet requirements of spinal implants and
      they need be further optimized. 3D printing technology makes process of the
      complex structure of prosthesis and individual customization possible and has
      broad development prospects. However, long production cycles and high cost of
      defect should be overcome. Although artificial vertebral body has achieved
      curative effect in treating spinal disease, there were reports of implant
      loosening or displacement. Combining with evaluation standards not unified, short
      follow-up time, its exact effect needs further observation.

PMID- 29457443
TI  - [Diagnosis and treatment of esophagustype cervical spondylosis].
AB  - Esophagustype cervical spondylosis is easily misdiagnosed or missed diagnosed for
      its lower incidence. The pathological basis manily concerned with compression of
      osteophyte for esophageal and tracheal wall and local inflammatory reaction. The
      diagnosis of disease is generally not difficult. Especially dynamic esophagogram
      could not only show degree of cervical degeneration and osteophyte shape, but
      also could clearly observe location and degree of osteophytosis indenting
      esophageal and tracheal. Recently, the treatment of esophagustype cervical
      spondylosis has been the focus of attention. It is generally believed that
      conservative treatment could alleviate disease but could not cure it. More and
      more scholars tend to treat disease by surgical resection of osteophyte to
      relieve compression for esophagus, and clinical symptoms could obviously
      improved. However, long-term follow up is lack, and further follow-up effect is
      lack of powerful support, anddifferent treatment methods and surgical procedures
      are lack of comparative research.

PMID- 29457445
TI  - Model for End-Stage Liver Disease and Seven Derivations to Prioritize Liver
      Transplant Candidates: Which Is the Winner?
AB  - OBJECTIVES: Under the present liver transplant policy, patients with the highest
      risk of death receive preference for organ placement. The aim of this study was
      to evaluate the Model for End-stage Liver Disease (MELD) and seven prognostic
      derivatives of this test for outcome prediction in cirrhotic patients on liver
      transplant wait lists. MATERIAL AND METHODS: The study included 416 patients
      (65.9% male; age 49 +/- 13.9 years) who were entered to liver transplant wait
      lists from January 2013 to October 2016. Study endpoints were 3-month, 6-month,
      and 1-year mortality. RESULTS: All prognostic models had acceptable overall
      performances (0.12 < Brier score < 0.21). The MELD-to-serum sodium ratio test
      outperformed its counterparts at all 3 endpoints. Estimated C statistics ranged
      from 0.77 to 0.83. The largest value at 3 months was for the 5-variable MELD
      score (0.83), and the largest value at 6 months (0.82) and 1 year (0.83) was for
      the MELD-albumin score. The Hosmer-Lemeshow goodness-of-fit test and calibration
      plots revealed underestimation for the entire range of predicted risk (P < .001).
      With decision curve analysis, the MELD-to-serum sodium ratio and United Kingdom
      Model for End-Stage Liver Disease scoring tests covered the most extensive range
      of optimal threshold probabilities. CONCLUSIONS: Although some derivations,
      including sodium and albumin, showed effective prioritization of liver transplant
      candidates, poor calibration statistics highlighted the need for a recalibration
      process as an inevitable prerequisite before daily clinical use of these tests at
      the individual level.

PMID- 29457444
TI  - [Effect of surface modification on biotribological properties of ultra-high
      molecular weight polyethylene artificial joints].
AB  - Friction and wear of ultra-high molecular weight polyethylene is a major cause of
      artificial joint failure. According to mechanism of surface modification method,
      friction reduction and wear-resistance properties of UHMWPE were improve by
      several kinds of surface modification methods. Meanwhile, this do not damage the
      internal structure and properties of UHMWPE. In the process, condition is easy to
      control and operation is simple. However, reaction time of radiation crosslinking
      method is too long, the material will be oxidized embrittlement; Monomer itself
      homopolymerization are seriously in the process of surface grafting; The
      injection layer of ion implantation methods is very thin and easy to be
      destroyed. Objective in order to provide a reference for further research on the
      biotribological properties of ultra-high molecular weight polyethylene artificial
      joints. At present, as the researches of UHMWPE material main focus on abrasion
      resistance, and application in the clinical trial is the focus of research, it
      has a wide prospect in the future.

PMID- 29457446
TI  - Roll-To-Roll Printing of Meter-Scale Composite Transparent Electrodes with
      Optimized Mechanical and Optical Properties for Photoelectronics.
AB  - Flexible transparent electrodes are an indispensable component for flexible
      optoelectronic devices. In this work, the meter-scale composite transparent
      electrodes (CTEs) composed of poly(3,4-ethylenedioxythiophene):polystyrene
      sulfonate (PEDOT:PSS) and Ag grid/polyethylene terephthalate (PET) with optimized
      mechanical and optical properties are demonstrated by slot-die roll-to-roll
      technique with solution printing method under a low cost ($15-20 per square
      meter), via control of the viscosity and surface energy of PEDOT:PSS ink as well
      as the printing parameters. The CTEs show excellent flexibility remaining 98% of
      the pristine value after bending 2000 times under various bending situations, and
      the square resistance ( Rs) of CTEs can be reduced to 4.5-5.0 Omega/sq with an
      appropriate transmittance. Moreover, the optical performances, such as haze,
      extinction coefficient, and refractive index, are investigated, as compared with
      indium tin oxide/PET, which are potential for the inexpensive optoelectronic
      flexible devices. The CTEs could be successfully employed in polymer solar cells
      with different areas, showing a maximal power conversion efficiency of 8.08%.

PMID- 29457447
TI  - Effects of Chain Orientation in Self-Organized Buffer Layers Based on Poly(3
      alkylthiophene)s for Organic Photovoltaics.
AB  - Surface-segregated monolayers (SSMs) based on two poly(3-alkylthiophene)s with
      semifluoroalkyl groups at either the side chains (P3DDFT) or one end of the main
      chain (P3BT-F17) were used as self-organized buffer layers at the electrode
      interfaces in bulk heterojunction (BHJ) organic photovoltaic devices. Both of the
      SSMs greatly shifted the vacuum levels of the BHJ films at the surface due to the
      aligned permanent dipole moments of the semifluoroalkyl chains. Hole extraction
      in the BHJ of poly(3-hexylthiophene) (P3HT):[6,6]-phenyl C61-butyric acid methyl
      ester (PCBM) became more efficient in the presence of the P3DDFT buffer layer,
      resulting in an improved power conversion efficiency. In contrast, the SSM of
      P3BT-F17 induced changes in the chain orientation of P3HT and the morphology of
      the BHJ films, resulting in decreased performance. These results indicate that
      the molecular design of polymer-based SSMs can affect not only the energy
      structure at the interface but also the morphology and the molecular orientations
      in the BHJs.

PMID- 29457448
TI  - Au/ZnSe-Based Surface Enhanced Infrared Absorption Spectroscopy as a Universal
      Platform for Bioanalysis.
AB  - A versatile and sensitive platform for label-free bioanalysis has been proposed
      on the basis of attenuated total reflection-surface enhanced infrared absorption
      spectroscopy (ATR-SEIRAS) using Au/ZnSe as the enhancement substrate that allows
      a wide spectral range down to 700 cm-1. Au nanoparticles are stably deposited on
      the surface of a ZnSe prism due to the formation of Au-Se bonds via electroless
      deposition, and the enhancement factor of the resultant Au/ZnSe substrate is
      about 2 times larger than that of the commonly used Au/Si substrate. As a
      demonstration, the Au/ZnSe-based SEIRAS has been applied to obtain abundant
      structural information in the fingerprint region and quantitative analysis of
      various biomolecular interactions such as DNA hybridization and immunoreaction
      without any labeling process.

PMID- 29457450
TI  - Graphdiyne Nanosheet-Based Drug Delivery Platform for Photothermal/Chemotherapy
      Combination Treatment of Cancer.
AB  - Nowadays, two-dimensional (2D) materials have attracted extensive attention as
      cancer drug delivery platforms owing to their unparalleled physicochemical
      properties and superior specific surface area. Graphdiyne (GDY) is a novel 2D
      carbon material. Compared with graphene, GDY not only has benzene rings composed
      of sp2-hybridized carbon atoms but also has acetylene units composed of sp
      hybridized carbon atoms; therefore, it possesses multiple conjugated electronic
      structures. Herein, we used doxorubicin (DOX) as a model drug to develop a GDY
      nanosheet-based drug delivery platform for a photothermal/chemotherapy
      combination in living mice. With a high photothermal conversion ability and drug
      loading efficiency, GDY/DOX under 808 nm laser irradiation showed a much higher
      cancer inhibition rate compared with solo therapy both in vitro and in vivo.
      Furthermore, GDY exhibited great biocompatibility and no obvious side effects, as
      shown by histopathological examination and serum biochemical analysis. For the
      first time, our work demonstrated a successful example of GDY for efficient
      photothermal/chemotherapy and suggests both safety and great promise for GDY in
      cancer treatment.

PMID- 29457451
TI  - Boosted Electrochemical Immunosensing of Genetically Modified Crop Markers Using
      Nanobody and Mesoporous Carbon.
AB  - The problems of environmental security and the potential risks of human health
      caused by transgenic crops have attracted much attention. Recent studies reveal 5
      enolpyruvylshikimate-3-phosphate synthase (EPSPS) from Agrobacterium sp. strain
      CP4 protein (CP4-EPSPS), which shows very high resistance to herbicide
      glyphosate, is a typical biomarker of genetically modified (GM) crops. For this
      reason, it is highly anticipated to devise a sensitive and convenient strategy to
      detect CP4-EPSPS protein in crops. Herein, we report a simple electrochemical
      immunosensor by coupling nanobody, ordered mesoporous carbon (OMC), and thionine
      (Th). As a capture agent, the nanobody was screened out from an immunized
      Bactrian camel, and exhibited superior properties with respect to conventional
      antibody, such as higher stability and stronger heat resistance. Moreover, OMC
      offered an effective platform with high surface area, electrical conductivity,
      and biocompatibility, which greatly facilitated the assembly of redox probe Th,
      and further coupling of large amount of capture nanobodies. As a result, the CP4
      EPSPS protein could be determined with high sensitivity and efficiency by
      differential pulse voltammetry (DPV) in a wide linear range from 0.001 to 100
      ng.mL-1 with a low detection limit of 0.72 pg.mL-1, which was more than 3 orders
      of magnitude lower than those of previously reported works. As an example, the
      proposed electrochemical immunosensor was successfully applied to spiked samples,
      demonstrating its great potential in CP4-EPSPS screening and detection.

PMID- 29457449
TI  - Catalytically Active Single-Chain Polymeric Nanoparticles: Exploring Their
      Functions in Complex Biological Media.
AB  - Dynamic single-chain polymeric nanoparticles (SCPNs) are intriguing, bioinspired
      architectures that result from the collapse or folding of an individual polymer
      chain into a nanometer-sized particle. Here we present a detailed biophysical
      study on the behavior of dynamic SCPNs in living cells and an evaluation of their
      catalytic functionality in such a complex medium. We first developed a number of
      delivery strategies that allowed the selective localization of SCPNs in different
      cellular compartments. Live/dead tests showed that the SCPNs were not toxic to
      cells while spectral imaging revealed that SCPNs provide a structural shielding
      and reduced the influence from the outer biological media. The ability of SCPNs
      to act as catalysts in biological media was first assessed by investigating their
      potential for reactive oxygen species generation. With porphyrins covalently
      attached to the SCPNs, singlet oxygen was generated upon irradiation with light,
      inducing spatially controlled cell death. In addition, Cu(I)- and Pd(II)-based
      SCPNs were prepared and these catalysts were screened in vitro and studied in
      cellular environments for the carbamate cleavage reaction of rhodamine-based
      substrates. This is a model reaction for the uncaging of bioactive compounds such
      as cytotoxic drugs for catalysis-based cancer therapy. We observed that the rate
      of the deprotection depends on both the organometallic catalysts and the nature
      of the protective group. The rate reduces from in vitro to the biological
      environment, indicating a strong influence of biomolecules on catalyst
      performance. The Cu(I)-based SCPNs in combination with the
      dimethylpropargyloxycarbonyl protective group showed the best performances both
      in vitro and in biological environment, making this group promising in biomedical
      applications.

PMID- 29457452
TI  - Multiple Stimuli-Responsive Fluorescent Sensor from Citric Acid and 1-(2
      Aminoethyl)piperazine.
AB  - Multiresponsive fluorescent supramolecular materials are quite interesting, for
      they combine the multiresponsiveness of supramolecules and the high sensitivity
      of fluorescent materials. Different from the multiresponsive supramolecular
      materials based on host-guest interactions, in this report, a supramolecular
      ionic network was fabricated by 1-(2-aminoethyl)piperazine and citric acids via
      ionic interactions. Despite the fact that there are no conventional chromophores,
      the obtained supramolecular ionic material can emit strong fluorescence. Most
      interestingly, the thin film of this supramolecular ionic material can change its
      fluorescent intensity in response to four external stimuli, including humidity,
      triethylamine, acetic acid, and temperature. Beneficial to the supramolecular
      ionic structure, this multiresponsive fluorescent sensor is self-healable. It is
      found that a new route has been opened to prepare the multiresponsive fluorescent
      sensors.

PMID- 29457453
TI  - Exquisite Enzyme-Fenton Biomimetic Catalysts for Hydroxyl Radical Production by
      Mimicking an Enzyme Cascade.
AB  - Hydrogen peroxide (H2O2) is a key reactant in the Fenton process. As a byproduct
      of enzymatic reaction, H2O2 can be obtained via catalytical oxidation of glucose
      using glucose oxidase in the presence of O2. Another oxidation product (gluconic
      acid) can suitably adjust the microenvironmental pH contributing to the Fe3+/Fe2+
      cycle in the Fenton reaction. Enzymes are extremely efficient at catalyzing a
      variety of reactions with high catalytic activity, substrate specificity, and
      yields in living organisms. Inspired by the multiple functions of natural
      multienzyme systems, an exquisite nanozyme-modified alpha-FeOOH/porous carbon
      (PC) biomimetic catalyst constructed by in situ growth of glucose oxidase
      mimicking Au nanoparticles and crystallization of adsorbed ferric ions within
      carboxyl into hierarchically PC is developed as an efficient enzyme-Fenton
      catalyst. The products (H2O2, ~4.07 mmol.L-1) of the first enzymatic reaction are
      immediately used as substrates for the second Fenton-like reaction to generate
      the valuable *OH (~96.84 MUmol.L-1), thus mimicking an enzyme cascade pathway.
      alpha-FeOOH nanocrystals, attached by C-O-Fe bondings, are encapsulated into the
      mesoporous PC frameworks, facilitating the electron transfer between alpha-FeOOH
      and the PC support and greatly suppressing iron leaching. This study paves a new
      avenue for designing biomimetic enzyme-based Fenton catalysts mimicking a natural
      system for *OH production.

PMID- 29457454
TI  - Rationally Designed, Multifunctional Self-Assembled Nanoparticles for Covalently
      Networked, Flexible and Self-Healable Superhydrophobic Composite Films.
AB  - For constructing bioinspired functional films with various superhydrophobic
      functions, including self-cleaning, anticorrosion, antibioadhesion, and oil-water
      separation, hydrophobic nanomaterials have been widely used as crucial structural
      components. In general, hydrophobic nanomaterials, however, cannot form strong
      chemical bond networks in organic-inorganic hybrid composite films because of the
      absence of chemically compatible binding components. Herein, we report the
      rationally designed, multifunctional self-assembled nanoparticles with tunable
      functionalities of covalent cross-linking and hydrophobicity for constructing
      three-dimensionally interconnected superhydrophobic composite films via a facile
      solution-based fabrication at room temperature. The multifunctional self
      assembled nanoparticles allow the systematic control of functionalities of
      composite films, as well as the stable formation of covalently linked
      superhydrophobic composite films with excellent flexibility (bending radii of 6.5
      and 3.0 mm, 1000 cycles) and self-healing ability (water contact angle > 150
      degrees , >=10 cycles). The presented strategy can be a versatile and effective
      route to generating other advanced functional films with covalently
      interconnected composite networks.

PMID- 29457455
TI  - Ultrathin kappa-Carrageenan/Chitosan Hydrogel Films with High Toughness and
      Antiadhesion Property.
AB  - Designing tough biopolymer-based hydrogels as structural biomaterials has both
      scientific and practical significances. We report a facile approach to prepare
      polysaccharide-based hydrogel films with remarkable mechanical performances and
      antiadhesion property. The hydrogel films with a thickness of 40-60 MUm were
      prepared by mixing aqueous solutions of kappa-carrageenan (kappa-CG) and
      protonated chitosan (CS), evaporating the solvent, and then swelling the casted
      film in water to achieve the equilibrium state. The obtained kappa-CG/CS gel
      films with a water content of 48-88 wt % possessed excellent mechanical
      properties with a breaking stress of 2-6.7 MPa and a breaking strain of 80-120%,
      superior to the most existing biopolymer-based hydrogels. The extraordinary
      mechanical properties of gel films obtained over a wide range of mass ratio of
      kappa-CG to CS should be rooted in the synergistic effect of ionic and hydrogen
      bonds between the kappa-CG and CS molecules. In addition, the tough gel films
      showed good self-recovery ability, biocompatibility, and cell antiadhesion
      property, making them promising as an artificial dura mater and diaphragm
      materials in the surgery. The design principle by incorporating multiple
      noncovalent bonds to toughen the biopolymer-based hydrogels should be applicable
      to other systems toward structural biomaterials with versatile properties.

PMID- 29457456
TI  - Functional Metathesis Catalyst Through Ring Closing Enyne Metathesis: One Pot
      Protocol for Living Heterotelechelic Polymers.
AB  - Enyne ring closing metathesis has been used to synthesize functional group
      carrying metathesis catalysts from a commercial (Ru-benzylidene) Grubbs'
      catalysts. The new Grubbs-type ruthenium carbene was used to synthesize living
      heterotelechelic ROMP polymers without any intermediate purification. Olefin
      metathesis with a mono substituted alkyne followed by ring closing metathesis
      with an allylic ether provided efficient access to new functional group carrying
      metathesis catalysts. Different functional benzylidene and alkylidene derivatives
      have been investigated in the synthesis of heterotelechelic polymers in one pot.

PMID- 29457457
TI  - Programming Hierarchical Self-Assembly of Patchy Particles into Colloidal
      Crystals via Colloidal Molecules.
AB  - Colloidal self-assembly is a promising bottom-up route to a wide variety of three
      dimensional structures, from clusters to crystals. Programming hierarchical self
      assembly of colloidal building blocks, which can give rise to structures ordered
      at multiple levels to rival biological complexity, poses a multiscale design
      problem. Here we explore a generic design principle that exploits a hierarchy of
      interaction strengths and employ this design principle in computer simulations to
      demonstrate the hierarchical self-assembly of triblock patchy colloidal particles
      into two distinct colloidal crystals. We obtain cubic diamond and body-centered
      cubic crystals via distinct clusters of uniform size and shape, namely,
      tetrahedra and octahedra, respectively. Such a conceptual design framework has
      the potential to reliably encode hierarchical self-assembly of colloidal
      particles into a high level of sophistication. Moreover, the design framework
      underpins a bottom-up route to cubic diamond colloidal crystals, which have
      remained elusive despite being much sought after for their attractive photonic
      applications.

PMID- 29457458
TI  - Amphiphilic Functionalized Acupuncture Needle as SERS Sensor for In Situ
      Multiphase Detection.
AB  - Surface enhanced Raman spectroscopy (SERS) is a powerful spectroscopic technique
      with unique vibrational fingerprints, making it an ideal candidate for in situ
      multiphase detection. However, it is a great challenge to determine how to guide
      the SERS sensor to target molecules of interest in multiphase heterogeneous
      samples with minimal disturbance. Here, we present a portable ultrasensitive and
      highly repeatable SERS sensor for in situ multiphase detection. The sensor is
      composed of commercial Ag acupuncture needle and PVP-Au nanoparticles (Au NPs).
      The PVP on the Au NPs can adsorb and induce the Au NPs into a highly uniform
      array on the surface of the Ag needle because of its adhesiveness and steric
      nature. The Au NPs-Ag Needle system (Au-AgN) holds a huge SERS effect, which is
      enabled by the multiple plasmonic couplings from particle-film and interparticle.
      The PVP, as the amphiphilic polymer, promotes the target molecules to adsorb on
      surface of the Au-AgN whether in the oil phase or in the water phase. In this
      work, the Au-AgN sensor was directly inserted into the multiphase system with the
      laser in situ detection, and SERS detection at different spots of the Au-AgN
      sensor provided Raman signal of targets molecule in the different phase. In situ
      multiphase detection can minimize the disturbance of sampling and provide more
      accurate information. The facile fabrication and amphiphilic functionalization
      make Au-AgN sensor as generalized SERS detection platform for on-site testing of
      aqueous samples, organic samples, even the multiphase heterogeneous samples.

PMID- 29457459
TI  - Spontaneous Aerobic Oxidation of 1,1,2,2-Tetrakis(N-methylpyridin- 4-ium)ethane
      Iodide to the Alkene and the Epoxide.
AB  - The tetrapyridinium salt 1 was found to undergo quantitative air oxidation upon
      dissolving it in water. The corresponding alkene and the epoxide were found as
      the only products of the oxidation. A mechanism that involves an alkyl
      hydroperoxide intermediate 1" undergoing a transformation that yields both
      products is proposed. Air oxidation of 1 shows the potential of the acceptor
      substituted alkanes to be used in the studies of mostly unknown direct
      epoxidation of single C-C bonds.

PMID- 29457460
TI  - Stressful Surfaces: Cell Metabolism on a Poorly Adhesive Substrate.
AB  - The adhesion and proliferation of cells are exquisitely sensitive to the nature
      of the surface to which they attach. Aside from cell counting, cell "health" on
      surfaces is typically established by measuring the metabolic rate with dyes that
      participate in the metabolic pathway or using "live/dead" assays with
      combinations of membrane permeable/impermeable dyes. The binary information
      gleaned from these tests-whether cells are attached or not, and whether they are
      living or dead-provides an incomplete picture of cell health. In the present
      work, proliferation rates and net metabolism of 3T3 fibroblasts seeded on
      "biocompatible" ultrathin polyelectrolyte multilayer films and on control tissue
      culture plastic were compared. Cells adhered to, and proliferated on, both
      surfaces, which were shown to be nontoxic according to live/dead assays. However,
      adhesion was poorer on the multilayer surface, illustrated by diffuse
      organization of the actin cytoskeleton and less-developed focal adhesions.
      Proliferation was also slower on the multilayer. When normalized for the total
      number of cells, it was shown that cells on multilayers experienced a five-day
      burst of metabolic stress, after which the metabolic rate approached that of the
      control surface. This initial state of high stress has not been reported or
      appreciated in studies of cell growth on multilayers, although the observation
      period for this system is usually a few days.

PMID- 29457461
TI  - Correction to "Single-Molecule Studies of Acidity Distributions in Mesoporous
      Aluminosilicate Thin Films".

PMID- 29457462
TI  - Determination of Site-Specific Phosphorylation Ratios in Proteins with Targeted
      Mass Spectrometry.
AB  - We show that parallel reaction monitoring (PRM) can be used for exact
      quantification of phosphorylation ratios of proteins using stable-isotope-labeled
      peptides. We have compared two different PRM approaches on a digest of a U87 cell
      culture, namely, direct-PRM (tryptic digest measured by PRM without any further
      sample preparation) and TiO2-PRM (tryptic digest enriched with TiO2 cartridges,
      followed by PRM measurement); these approaches are compared for the following
      phosphorylation sites: neuroblast differentiation-associated protein (AHNAK S5480
      p), calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D
      T337-p), and epidermal growth factor receptor (EGFR S1166-p). A reproducible
      percentage of phosphorylation could be determined (CV 6-13%) using direct-PRM or
      TiO2-PRM. In addition, we tested the approaches in a cell culture experiment in
      which U87 cells were deprived of serum. As a "gold standard" we included immune
      precipitation of EGFR followed by PRM (IP-PRM). For EGFR (S1166) and AHNAK
      (S5480) a statistical significant change in the percentage of phosphorylation
      could be observed as a result of serum deprivation; for EGFR (S1166) this change
      was observed for both TiO2-PRM and IP-PRM. The presented approach has the
      potential to multiplex and to quantify the ratio of phosphorylation in a single
      analysis.

PMID- 29457463
TI  - ICRP Publication 138: Ethical Foundations of the System of Radiological
      Protection.
AB  - Abstract -: Despite a longstanding recognition that radiological protection is
      not onlya matter of science, but also ethics, ICRP publications have rarely
      addressed theethical foundations of the system of radiological protection
      explicitly. The purposeof this publication is to describe how the Commission has
      relied on ethical values,either intentionally or indirectly, in developing the
      system of radiological protectionwith the objective of presenting a coherent view
      of how ethics is part of this system.In so doing, it helps to clarify the
      inherent value judgements made in achieving theaim of the radiological protection
      system as underlined by the Commission inPublication 103. Although primarily
      addressed to the radiological protection community,this publication is also
      intended to address authorities, operators, workers,medical professionals,
      patients, the public, and its representatives (e.g. NGOs) actingin the interest
      of the protection of people and the environment. This publicationprovides the key
      steps concerning the scientific, ethical, and practical evolutions ofthe system
      of radiological protection since the first ICRP publication in 1928. It
      thendescribes the four core ethical values underpinning the present system:
      beneficence/non-maleficence, prudence, justice, and dignity. It also discusses
      how these coreethical values relate to the principles of radiological protection,
      namely justification,optimisation, and limitation. The publication finally
      addresses key procedural valuesthat are required for the practical implementation
      of the system, focusing onaccountability, transparency, and inclusiveness. The
      Commission sees this publicationas a founding document to be elaborated further
      in different situations andcircumstances.

PMID- 29457464
TI  - Assessment of DNA Methylation Patterns in the Bone and Cartilage of a Nonhuman
      Primate Model of Osteoarthritis.
AB  - Objective Osteoarthritis (OA) affects humans and several other animals. Thus, the
      mechanisms underlying this disorder, such as specific skeletal tissue DNA
      methylation patterns, may be evolutionary conserved. However, associations
      between methylation and OA have not been readily studied in nonhuman animals.
      Baboons serve as important models of disease and develop OA at rates similar to
      those in humans. Therefore, this study investigated the associations between
      methylation and OA in baboons to advance the evolutionary understanding of OA.
      Design Trabecular bone and cartilage was collected from the medial condyles of
      adult female baboon femora, 5 with and 5 without knee OA. The Infinium
      HumanMethylation450 BeadChip (450K array) was used to identify DNA methylation
      patterns in these tissues. Results Approximately 44% of the 450K array probes
      reliably align to the baboon genome, contain a CpG site of interest, and maintain
      a wide distribution throughout the genome. Of the 2 filtering methods tested,
      both identified significantly differentially methylated positions (DMPs) between
      healthy and OA individuals in cartilage tissues, and some of these patterns
      overlap with those previously identified in humans. Conversely, no DMPs were
      found between tissue types or between disease states in bone tissues. Conclusions
      Overall, the 450K array can be used to measure genome-wide DNA methylation in
      baboon tissues and identify significant associations with complex traits. The
      results of this study indicate that some DNA methylation patterns associated with
      OA are evolutionarily conserved, while others are not. This warrants further
      investigation in a larger and more phylogenetically diverse sample set.

PMID- 29457465
TI  - Further Evaluation of a Practitioner Model for Increasing Eye Contact in Children
      With Autism.
AB  - Cook et al. recently described a progressive model for teaching children with
      autism spectrum disorder (ASD) to provide eye contact with an instructor
      following a name call. The model included the following phases: contingent praise
      only, contingent edibles plus praise, stimulus prompts plus contingent edibles
      and praise, contingent video and praise, schedule thinning, generalization
      assessments, and maintenance evaluations. In the present study, we evaluated the
      extent to which modifications to the model were needed to train 15 children with
      ASD to engage in eye contact. Results show that 11 of 15 participants acquired
      eye contact with the progressive model; however, eight participants required one
      or more procedural modifications to the model to acquire eye contact. In
      addition, the four participants who did not acquire eye contact received one or
      more modifications. Results also show that participants who acquired eye contact
      with or without modifications continued to display high levels of the behavior
      during follow-up probes. We discuss directions for future research with and
      limitations of this progressive model.

PMID- 29457466
TI  - Feasibility of an Alzheimer's disease knowledge intervention in the Latino
      community.
AB  - BACKGROUND: Latinos experience disparities in Alzheimer's disease (AD) knowledge.
      The aim of this study was to explore the feasibility of a 45-minute culturally
      tailored AD knowledge presentation for professionals serving the Latino community
      and Latinos served by Latino community organizations. METHODS: One-session AD
      knowledge lunch-and-learn events were conducted with 40 professionals and 37
      served Latinos. Participants received a pre-post survey including questions on
      satisfaction, a subjective AD knowledge question and a 14 item objective AD
      knowledge questionnaire. RESULTS: Professionals (54.3%) and served Latinos
      (94.6%) reported the session as being very enjoyable and increased in objective
      AD knowledge (2.1 and 2.5 units, p < .001) and subjective knowledge (1.1 and 1.7
      units; p < .001). DISCUSSION: A brief in-person culturally-tailored session of AD
      education increases short-term AD knowledge and is perceived as interesting and
      useful among professionals serving the Latino community and Latinos served by
      Latino community organizations.

PMID- 29457467
TI  - Civil Forensic Psychiatry - part 3: practical aspects of managing a medico-legal
      practice.
AB  - OBJECTIVES: This is the third in a series of papers on Civil Forensic Psychiatry
      and provides practical advice for forensic psychiatrists, general psychiatrists
      and trainees who are expanding or contemplating a medico-legal aspect to their
      practice. CONCLUSIONS: Attention to the practice setting, office layout,
      recording of information, management of documentation, screening of briefs and
      proper timetabling can improve safety, quality, reliability and workload
      manageability.

PMID- 29457468
TI  - Experiences of racism, sexual objectification and alcohol use among gay and
      bisexual men of colour.
AB  - OBJECTIVE: Previous research has shown that experiences of racial discrimination
      and sexual objectification are associated with health risk behaviours among gay
      and bisexual men of colour. However, little is known about whether racial
      discrimination and sexual objectification are associated with alcohol use among
      this population. This community-based study examined the association between
      racial discrimination, sexual objectification and alcohol use in a sample of 369
      gay and bisexual men of colour (Black/African/Caribbean, Latino/Latin American,
      South Asian, and East and Southeast Asian) in Toronto. DESIGN: Data were drawn
      from an online survey designed to examine issues of racism, homophobia, health
      and well-being among gay and bisexual men of colour in Toronto. Regression
      analysis assessed the relationship between scores on the Racism and Life
      Experiences Scale, Sexual Objectification Scale, and the CAGE questionnaire (a
      screen for alcohol use disorder). RESULTS: Multivariable logistic regression
      analyses revealed that experiences of racism and sexual objectification are
      significantly and positively associated with a screening for alcohol use
      disorder. The interactions between Latino/Latin American race/ethnicity and
      experience of sexual objectification were also positively associated with a
      screening for alcohol use disorder. CONCLUSIONS: Health professionals should
      consider the role of racial discrimination and sexual objectification within the
      context of risk and treatment for alcohol use disorders, harm reduction, and HIV
      prevention for gay and bisexual men of colour.

PMID- 29457469
TI  - Development of an operational manual for a consultation-liaison psychiatry
      service.
AB  - OBJECTIVES: Consultation-liaison psychiatry (CLP) services sit between mental
      health and the general hospital, and risk being poorly understood by both
      systems. The aim of this study was to develop an operational manual for a CLP
      service, which defined functions and governance. METHODS: The CLP literature was
      reviewed with a focus on descriptions of CLP roles, organisational processes,
      quality measures and service development. The CLP team held service planning
      meetings and met with members of the mental health and hospital executives. Site
      visits and collaboration with other CLP services occurred in defining the roles
      of the CLP service and organisational governance. RESULTS: A CLP operational
      document was developed, including a description of the service, its functions,
      staff roles and governance. Procedural information such as the CLP timetable,
      referral process, triage and assessment, documentation, activity recording,
      quality assurance and relevant policies were outlined. CONCLUSIONS: The
      development of a dedicated operational manual for CLP clarified the roles,
      functions and governance of CLP within the general hospital and mental health
      systems. The development process facilitated the engagement of key clinicians and
      administrators of these systems, the determination of quality improvement targets
      and greater transparency and accountability.

PMID- 29457470
TI  - Shared decision-making in psychiatry: a study of patient attitudes.
AB  - OBJECTIVES: Shared decision-making (SDM) is promoted as beneficial in mental
      healthcare, despite a dearth of supportive evidence. We aimed to obtain patients'
      perspective on SDM in a 'real world' hospital sample. METHODS: Structured
      validated questionnaires were used to examine SDM with regard to treatment
      choices, and whether SDM influences attitudes towards treatment. The Mini-Mental
      State Examination was used to assess decision-making capacity. RESULTS: A total
      of 109 individuals participated, with 60% reporting experiencing SDM. SDM
      positively correlated with positive attitudes to medication. Those detained under
      the Mental Health Act had lower levels of SDM. CONCLUSIONS: SDM leads to more
      positive attitudes towards medication and may improve adherence with treatment.
      SDM may particularly benefit those subject to involuntary treatment and is not
      onerous to practice.

PMID- 29457471
TI  - Beck Depression Inventory as a screening tool for depression in chronic
      haemodialysis patients.
AB  - OBJECTIVES: To evaluate the psychometric properties of the Beck Depression
      Inventory (BDI) and Cognitive Depression Index (CDI) as a potential screening
      tool for major depression in haemodialysis (HD) patients. METHODS: Forty-five HD
      patients completed both the BDI/CDI and diagnostic interview. The interview was
      conducted by two experienced clinicians and was based on DSM-IV criteria. The
      sensitivity, specificity and positive (PPV) and negative (NPV) predictive values
      were then calculated. RESULTS: A diagnosis of depression was found in 6 of the 45
      participants (13.3%). Optimal cut-offs were >=18 for the BDI (sensitivity 1.0,
      specificity 0.90, PPV 0.60, NPV 1.0) and >=11 for the CDI (sensitivity 1.0,
      specificity 0.92, PPV 0.67, NPV 1.0). CONCLUSIONS: Both the BDI and CDI were
      shown to be acceptable screening tools for depression in this population of
      chronic HD patients. The recommended cut-off scores for both scales are higher
      than those suggested for the general population and slightly higher than
      previously found in the chronic kidney disease literature, suggesting that
      altered thresholds are required when using these screening tools amongst HD
      patients.

PMID- 29457473
TI  - Going the distance: reviewing antipsychotic depot or long-acting injectable
      treatments in Australasia.
AB  - OBJECTIVES: The aim of this study is to provide an opinion paper reviewing the
      role of depot or long-acting injectable (LAI) antipsychotic medications, with
      comments on individual newer LAIs such aripiprazole maintena and paliperidone
      palmitate. In particular, we share our recent experience of using paliperidone
      three-monthly LAI. We also reflect on the associated benefits and potential harms
      of LAIs, and when they may be used. CONCLUSIONS: LAI antipsychotics are an
      important and arguably under-utilised therapeutic option, particularly where
      medication adherence is a priority, and where an informed patient opts for this
      formulation. Paliperidone is the first three-monthly LAI antipsychotic, and as
      such represents a significant advance in the range of treatment choices.

PMID- 29457474
TI  - The Importance of Calibration in Clinical Psychology.
AB  - Accuracy has several elements, not all of which have received equal attention in
      the field of clinical psychology. Calibration, the degree to which a
      probabilistic estimate of an event reflects the true underlying probability of
      the event, has largely been neglected in the field of clinical psychology in
      favor of other components of accuracy such as discrimination (e.g., sensitivity,
      specificity, area under the receiver operating characteristic curve). Although it
      is frequently overlooked, calibration is a critical component of accuracy with
      particular relevance for prognostic models and risk-assessment tools. With
      advances in personalized medicine and the increasing use of probabilistic (0% to
      100%) estimates and predictions in mental health research, the need for careful
      attention to calibration has become increasingly important.

PMID- 29457475
TI  - Civil forensic psychiatry - Part 2: specific issues.
AB  - OBJECTIVES: This paper describes the main areas of civil forensic psychiatry (FP)
      and the skills required by psychiatric experts. Some specific areas of civil FP
      are discussed, including tort law reform, reliability of psychiatric evidence,
      contentious psychiatric disorders, and the many domains of civil FP. CONCLUSIONS:
      Civil FP is an important sub-specialty component of forensic psychiatry that
      requires greater emphasis in the training and continuing education of
      psychiatrists. A process of accrediting psychiatrists as having competency in
      advanced civil FP may be of value.

PMID- 29457478
TI  - The interrelationships among pain interference, depressive symptoms, loneliness,
      and employment status: a moderated mediation study.
AB  - OBJECTIVE: To explore the mediating effect of loneliness on the relationship
      between pain interference and depressive symptoms and to determine whether this
      mechanism is contingent on employment status. DESIGN: Cross-sectional study.
      SUBJECTS: A total of 876 adult caregivers of adolescents living in extremely
      impoverished conditions. ANALYSIS: Mediation and moderated mediation analyses
      using standard path-analytic approaches. RESULTS: The mean age of the sample was
      39.0 (SD = 12.8) years and 80.7% ( n = 707) identified as female. Almost half
      (48.9%, n = 425) of the participants did not report any pain, while 32.5% ( n =
      285) reported non-disabling pain, and 19.0% ( n = 166) reported disabling pain.
      The mean depressive symptoms score was 16.20 (SD = 10.6), and the mean loneliness
      score was 40.09 (SD = 10.5). Loneliness mediated the effect of both non-disabling
      and disabling pain on depressive symptoms. However, the indirect effect of pain
      interference on depressive symptoms through loneliness was more pronounced among
      participants reporting disabling pain (coefficient, 2.11; Boot 95% confidence
      interval (CI) (1.25-3.01)) than non-disabling pain (coefficient, 0.99; Boot 95%
      CI (0.25-1.76)). Moderated mediation results showed that the indirect effect of
      pain interference on depressive symptoms, via loneliness varied in magnitude as a
      function of employment status among participants reporting disabling pain but not
      those reporting non-disabling pain. CONCLUSION: Loneliness provides an important
      link in the relationship between depressive symptoms and pain interference.
      Furthermore, employment status is an important factor to consider, especially
      among individuals reporting disabling pain with comorbid depressive symptoms.

PMID- 29457477
TI  - Enabling choice, recovery and participation: evidence-based early intervention
      support for psychosocial disability in the National Disability Insurance Scheme.
AB  - OBJECTIVES:: The aim of this study was to identify the most effective
      interventions for early intervention in psychosocial disability in the National
      Disability Insurance Scheme (NDIS) through an evidence review. METHODS:: A series
      of rapid reviews were undertaken to establish possible interventions for
      psychosocial disability, to develop our understanding of early intervention
      criteria for the NDIS and to determine which interventions would meet these
      criteria. RESULTS:: Three interventions (social skills training, supported
      employment and supported housing) have a strong evidence base for effectiveness
      in early intervention in people with psychosocial disability, with the potential
      for adoption by the NDIS. They support personal choice and recovery outcomes.
      Illness self-management, cognitive remediation and cognitive behavioural therapy
      for psychosis demonstrate outcomes to mitigate impairment. The evidence for
      family psycho-education is also very strong. CONCLUSIONS:: This review identified
      evidence-based, recovery-oriented approaches to early intervention in
      psychosocial disability. They meet the criteria for early intervention in the
      NDIS, are relevant to participants and consider their preferences. Early
      intervention has the potential to save costs by reducing participant reliance on
      the scheme.

PMID- 29457481
TI  - Selection and Use of Health Services for Infants' Needs by Indigenous Mothers in
      Canada: Integrative Literature Review.
AB  - In Canada, Indigenous infants experience significant health disparities when
      compared to non-Indigenous infants, including significantly higher rates of birth
      complications and infant mortality rates. The use of primary health care is one
      way to improve health outcomes; however, Indigenous children may use health
      services less often than non-Indigenous children. To improve health outcomes
      within this growing population, it is essential to understand how caregivers,
      defined here as mothers, select and use health services in Canada. This
      integrative review is the first to critique and synthesize what is known of how
      Indigenous mothers in Canada experience selecting and using health services to
      meet the health needs of their infants. Themes identified suggest both Indigenous
      women and infants face significant challenges; colonialism has had, and continues
      to have, a detrimental impact on Indigenous mothering; and very little is known
      about how Indigenous mothers select and use health services to meet the health of
      their infants. This review revealed significant gaps in the literature and a need
      for future research. Suggestions are made for how health providers can better
      support Indigenous mothers and infants in their use of health services, based on
      what has been explored in the literature to date.

PMID- 29457482
TI  - Dark and Bright-Two Sides of Family-Centered Care in the NICU: A Qualitative
      Study.
AB  - Nurses in the Neonatal Intensive Care Unit (NICU) have an important role in
      implementing family-centered care (FCC). The aim of the study was to explore the
      lived experiences of NICU nurses on implementing FCC. An interpretative
      phenomenological study was conducted and 11 employed nurses were interviewed from
      April 2015 to February 2016. The data were analyzed through the Diekelmann,
      Allen, and Tanner approach. Four main themes of "strain to achieve stability,"
      "bewildered by taking multiple roles," "accepting the family," and "reaching
      bright horizon" were extracted. This study provided deeper understanding about
      nurses' perceptions of FCC implementation. In Muslim developing countries, FCC
      implementation is challenging and nurses are under extra pressure because of a
      shortage in nursing workforce; however, having positive experiences with family
      participation and valuing theism beliefs allowed them to support family
      involvement. Support of nurses to take FCC strategies in the NICU is needed by
      officials overseeing the health care system.

PMID- 29457483
TI  - Sensitivity of the Saline Load Test for Traumatic Arthrotomy of the Ankle With
      Ankle Arthroscopy Simulation.
AB  - BACKGROUND: The saline load test has been used to evaluate for traumatic
      arthrotomy in orthopedics. The purpose of this study was to determine the volume
      of saline required to detect traumatic arthrotomy of the ankle. METHODS: Forty
      two patients undergoing elective ankle arthroscopy were prospectively enrolled.
      For each patient, a standard 4-mm anteromedial portal was established. Next, an
      18-gauge needle was inserted at the site of the anterolateral portal. Sterile
      saline was slowly injected through the needle until saline extravasated from the
      anteromedial portal. Saline volumes at the time of extravasation were recorded
      and analyzed. RESULTS: The saline volume required to achieve extravasation ranged
      from 0.2 to 60.0 mL. The median saline volume required to achieve extravasation
      was 9.7 mL (interquartile range, 3.8-29.6 mL); however, 5 of 42 patients required
      volumes between 50.0 and 60.0 mL. A total of 50.0 mL was required to achieve 90%
      sensitivity, 55.0 mL to achieve 95% sensitivity, and 60.0 mL to achieve 99%
      sensitivity. CONCLUSIONS: The previously recommended 30 mL of saline required to
      reliably detect traumatic arthrotomy of the ankle may be too small a volume.
      CLINICAL RELEVANCE: The present study suggests that clinicians should attempt to
      inject 60 mL of saline to effectively rule out a traumatic arthrotomy injury.
      Because of the study's methods involving an anteromedial arthrotomy with
      anterolateral saline injection, these findings may be most valid for arthrotomies
      on the medial side of the ankle.

PMID- 29457484
TI  - Cryosurgery + 5% 5-Fluorouracil for Treatment of Superficial Basal Cell Carcinoma
      and Bowen's Disease [Formula: see text].
AB  - BACKGROUND: Superficial basal cell carcinoma (sBCC) and squamous cell carcinoma
      in situ (SCCis) are 2 types of nonmelanoma skin cancers (NMSCs) that are amenable
      to treatment with topical 5-fluorouracil, cryosurgery, or topical imiquimod,
      among other destructive and surgical modalities. There are few studies examining
      the effectiveness of combination therapy with 5% 5-fluorouracil and cryosurgery
      for the treatment of sBCC and SCCis. OBJECTIVES: Our objective was to study the
      clinical cure rate achieved with the regimen of cryosurgery and a 3-week course
      of 5% 5-fluorouracil in the treatment of biopsy-proven sBCC and SCCis. METHODS: A
      retrospective chart review of patients treated with cryosurgery and a 3-week
      course of 5% 5-fluorouracil was performed. Immunocompetent patients with biopsy
      proven sBCC or SCCis who completed the treatment and attended a follow-up
      appointment at 6 months were included in the study. RESULTS: On clinical
      examination, 30 sBCC lesions of the 34 that were assessed and 31 SCCis lesions of
      the 33 that were assessed demonstrated no evidence of recurrence. The clinical
      cure rates were found to be 73% (sBCC) and 82% (SCCis), with the inclusion of
      patients that were lost to follow-up. CONCLUSIONS: This approach may represent a
      suitable option for select patients for the treatment of SCCis. Further studies
      with a longer follow-up duration, documentation of histologic cure, and
      tolerability of this regimen for SCCis are needed. The effectiveness of
      cryosurgery and 5-fluorouracil for sBCC requires further study.

PMID- 29457485
TI  - Atopy Associated With Positive Patch Test and Possible Allergic Contact
      Dermatitis.
AB  - BACKGROUND: Atopy is a genetic predisposition to the development of allergic
      reactions and the increased production of immunoglobulin E (IgE) upon exposure to
      environmental antigens. Clinical manifestations of atopy include asthma, atopic
      dermatitis (AD), and allergic rhinoconjunctivitis (ARC). OBJECTIVE: To determine
      if cutaneous delayed hypersensitivity reactions (CDHRs) as assessed by patch
      testing are higher among patients with a history of atopy and with a familial
      predisposition to atopy. METHODS: For this study, we reviewed the patch test
      database of the UBC Contact Dermatitis Clinic over a 4-year time span. A personal
      history of asthma, AD, and ARC was recorded. In addition, a family history was
      obtained and manifestations of atopy in family members were noted. RESULTS: A
      total of 1515 patients were included in this study. Our data show that the odds
      ratio (OR) of a positive patch test with a personal history of atopy was 1.39,
      while the OR of a positive patch test with a family history of atopy was 1.69.
      Conversely, a personal history of respiratory atopy did not significantly affect
      the probability of a positive patch test, with an OR of 1.03. CONCLUSION: We
      conclude from our study that patients with a personal or family history of atopy
      have an increased risk of allergic contact dermatitis (ACD). These results
      provide further evidence for the link between atopy and ACD and suggest that
      children of atopic parents should avoid potential contact allergens and would
      likely benefit from prophylactic emollient use.

PMID- 29457486
TI  - Case Report of Empagliflozin-Induced Cutaneous Polyarteritis Nodosa.
AB  - Polyarteritis nodosa (PAN) is a rare vasculitis affecting medium-sized vessels.
      Cutaneous PAN is a clinical variant, and we report the first case of
      empagliflozin-induced cutaneous PAN in a 69-year-old man. After starting
      empagliflozin, the patient presented with tender subcutaneous nodules on his
      legs, which showed a medium-sized vessel vasculitis on histopathology. Upon
      cessation of this medication, he had full resolution of these nodules. This case
      illustrates that empagliflozin can induce cutaneous PAN, and further attention to
      this medication's association with cutaneous PAN is warranted.

PMID- 29457487
TI  - Dementia management strategies associated with neuropsychiatric symptoms of
      elderly people with Alzheimer's disease.
AB  - This study aims to investigate the association between management and
      communication strategies and the presence of neuropsychiatric symptoms presented
      by elderly people with Alzheimer's disease. One hundred and thirty-four family
      caregivers answered a questionnaire with socio-demographic data and questions
      regarding the care context, the Small Communication Strategies Scale, the
      Dementia Management Strategy Scale, and the Neuropsychiatric Inventory.
      Caregivers used the criticism management strategy more when the elderly presented
      hallucination, agitation, depression, anxiety, irritability, nighttime behavior,
      and appetite abnormalities. The encouragement strategy was more significantly
      used only in the presence of euphoria/elation. The caregivers who used the most
      active management strategy were those who cared for the elderly with delirium,
      hallucination, agitation, depression, anxiety, irritability, and appetite and
      eating abnormalities. The use of communication strategies did not differ between
      groups with or without neuropsychiatric symptoms. It is concluded that criticism
      management and active management strategies are strongly associated with
      neuropsychiatric symptoms. The results of this study may be useful for planning
      treatment interventions that aim to modify the use of management strategies used
      by caregivers.

PMID- 29457488
TI  - Referral patterns and implementation costs of the Partners in Recovery initiative
      in Gippsland: learnings for the National Disability Insurance Scheme.
AB  - OBJECTIVE:: The purpose of this paper is to provide some learnings for the NDIS
      from the referral pattern and cost of implementing the Partners in Recovery
      initiative of Gippsland. METHOD:: Information on referral areas made for each
      consumer was collated from support facilitators. Cost estimates were determined
      using budget estimates, administrative costs and a literature review and are
      reported from a government perspective. RESULTS:: Sixty-three per cent of all
      referrals were made to organisations that provided multiple types of services.
      Thirty-one per cent were to Mental Health Community Support Services. Eighteen
      per cent of referrals were made to clinical mental health services. The total
      cost of providing the service for a consumer per year (set-up and ongoing) was
      estimated to be AUD$15,755 and the ongoing cost per year was estimated to be
      AUD$13,434. The cost of doing nothing is likely to cost more in the longer term,
      with poor mental health outcomes such as hospital admission, unemployment
      benefits, prison, homelessness and psychiatric residential care. CONCLUSIONS::
      Supporting recovery in persons with Severe and Persistent Mental Illness is
      likely to be economically more beneficial than not doing so. Recovery can be
      better supported when frequently utilised services are co-located. These might be
      some learnings for the NDIS.

PMID- 29457489
TI  - Shingrix: The New Adjuvanted Recombinant Herpes Zoster Vaccine.
AB  - OBJECTIVES: To review the immunogenicity, efficacy, and safety of the herpes
      zoster subunit vaccine (HZ/su) for use in adult patients for the prevention of
      shingles. DATA SOURCES: A literature search through PubMed was conducted (June
      2008 to October 2017) using the terms shingles vaccine and varicella zoster
      virus. References from retrieved articles and the prescribing information were
      also reviewed for any additional material. STUDY SELECTION/DATA EXTRACTION: The
      literature search was limited to human studies published in English. Randomized
      controlled, multicenter trials were reviewed and included to evaluate the safety
      and efficacy of HZ/su. Literature on the epidemiology and pathology of herpes
      zoster virus infections and recommendations from the Advisory Committee on
      Immunization Practices (ACIP) were also reviewed. DATA SYNTHESIS: HZ/su is a new
      adjuvanted recombinant vaccine approved by the Food and Drug Administration for
      the prevention of herpes zoster in adults 50 years of age and older. HZ/su
      significantly reduced the risk of developing herpes zoster by more than 90% as
      compared with placebo and displayed a comparable adverse effect profile. The most
      common local adverse events were injection site pain, redness, and swelling, and
      the most common systemic adverse events were myalgia, fatigue, and headache. The
      ACIP recommends the routine use of HZ/su as the preferred vaccine for the
      prevention of herpes zoster in immunocompetent adults 50 years of age and older.
      CONCLUSIONS: Based on published immunogenicity, efficacy, and safety data, as
      well as the recent recommendations by the ACIP, HZ/su should be included on both
      hospital and community pharmacy formularies and recommended to all
      immunocompetent patients older than 50 years to prevent herpes zoster.

PMID- 29457490
TI  - Demonstration of Resistant or Wild-Type Virus in Recurrent Viremia After
      Ganciclovir-Resistant Cytomegaloviral Infection.
AB  - BACKGROUND: Ganciclovir-resistant cytomegalovirus (GR-CMV) is a serious
      complication of transplantation. Recurrence after primary infection is common.
      Little is known about CMV drug resistance and latency. OBJECTIVE: Review CMV
      genotype during episodes of recurrent CMV viremia after prior documentation of
      ganciclovir resistance to evaluate if resistance is redemonstrated. METHODS: All
      adult transplant recipients with history of GR-CMV viremia from January 1, 2011,
      to December 31, 2015, were screened; those with subsequent laboratory evidence of
      recurrent CMV viremia and genotyping were included. RESULTS: A total of 23
      patients had genetically confirmed GR-CMV within the study time period; 14 were
      excluded due to lack of repeat resistance testing at recurrence and 4 due to of
      lack of negativity between testing, leaving 5 patients with 7 episodes of
      recurrent viremia to evaluate. At first recurrent viremia, 4 patients (80%)
      demonstrated resistant genotype; 1 patient had wild type. Two patients went on to
      have a second viremia recurrence; both demonstrated wild-type genotype, despite
      the fact that the first recurrence in these patients was resistant genotype.
      CONCLUSION: In transplant recipients with history of GR-CMV, it appears that
      there is strain variability in latency: repeat genetic testing in patients with
      recurrent viremia after GR-CMV should be conducted. In the setting of wild-type
      repopulation, use of GCV should be considered.

PMID- 29457492
TI  - The Risk of Community-Acquired Enteric Infection in Proton Pump Inhibitor
      Therapy: Systematic Review and Meta-analysis.
AB  - BACKGROUND: Previous meta-analyses suggest that users of proton pump inhibitors
      (PPIs) have a higher risk of developing enteric infections compared with
      nonusers. These previous meta-analyses have considerable heterogeneity, and it is
      not clear whether the effect of PPIs is different for different types of
      microorganisms. OBJECTIVE: The aim of this study is to update previous meta
      analyses, concentrating on enteric infection in community settings and exploring
      potential sources of heterogeneity. METHODS: A systematic search was conducted on
      electronic databases (all available years until November 2017). PubMed, EMBASE,
      Cochrane, and Web of Science were searched using specific keywords related to PPI
      therapy and community-acquired enteric infection. Eligible studies were selected
      based on prespecified criteria. RESULTS: A total of 9 observational studies
      evaluating community-acquired enteric infection were eligible, including 12
      separate analyses. The meta-analysis showed that PPI users have an increased risk
      of developing community-acquired enteric infection (pooled odds ratio [OR] =
      4.28; 95% CI = 3.01-6.08). There was significant heterogeneity between the
      studies ( I2 = 85%; P < 0.001), which was partly explained by type of
      microorganism. The strength of the association was similar for Salmonella (pooled
      OR = 4.84; 95% CI = 2.75-8.54; I2 = 58.7%; P = 0.064) and Campylobacter (pooled
      OR = 5.09; 95% CI = 3-8.64; I2 = 81%; P < 0.001) but lower for studies that
      combined all bacteria (pooled OR = 2.42; 95% CI = 0.96-6.14; I2 = 94.3%; P <
      0.001). CONCLUSION: PPI users have an increased risk of developing community
      acquired enteric infections compared with nonusers. The heterogeneity was
      partially explained by type of microorganism; the association is stronger for
      Salmonella and Campylobacter than for all bacteria combined.

PMID- 29457491
TI  - Critical Care Pharmacists and Medication Management in an ICU Recovery Center.
AB  - BACKGROUND: Many patients experience complications following critical illness;
      these are now widely referred to as post-intensive care syndrome (PICS). An
      interprofessional intensive care unit (ICU) recovery center (ICU-RC), also known
      as a PICS clinic, is one potential approach to promoting patient and family
      recovery following critical illness. OBJECTIVES: To describe the role of an ICU
      RC critical care pharmacist in identifying and treating medication-related
      problems among ICU survivors. METHODS: A prospective, observational cohort study
      was conducted of all outpatient appointments of a tertiary care hospital's ICU-RC
      between July 2012 and December 2015. The pharmacist completed a full medication
      review, including medication reconciliation, interview, counseling, and resultant
      interventions, during the ICU-RC appointment. RESULTS: Data from all completed
      ICU-RC visits were analyzed (n = 62). A full medication review was performed in
      56 (90%) of these patients by the pharmacist. The median number of pharmacy
      interventions per patient was 4 (interquartile range = 2, 5). All 56 patients had
      at least 1 pharmacy intervention; 22 (39%) patients had medication(s) stopped at
      the clinic appointment, and 18 (32%) patients had new medication(s) started. The
      pharmacist identified 9 (16%) patients who had an adverse drug event (ADE); 18
      (32%) patients had ADE preventive measures instituted. An influenza vaccination
      was administered to 13 (23%) patients despite an inpatient protocol to ensure
      influenza vaccination prior to discharge. A pneumococcal vaccination was
      administered to 2 (4%) patients. CONCLUSIONS: Use of a critical care pharmacist
      resulted in the identification and treatment of multiple medication-related
      problems in an ICU-RC as well as implementation of preventive measures.

PMID- 29457493
TI  - Impact of Vitamin D Supplementation on Attention-Deficit Hyperactivity Disorder
      in Children.
AB  - BACKGROUND: The role of nutrients and dietary factors in attention-deficit
      hyperactivity disorder (ADHD) remains unclear. OBJECTIVES: The primary objective
      was to evaluate the serum vitamin D level in children with a diagnosis of ADHD.
      The secondary objective was to detect the effect of vitamin D supplementation on
      cognitive function in those with vitamin D deficiency. METHODS: A total of 50
      children with ADHD and 40 healthy controls were included in the study. We
      measured the serum level of vitamin D. Patients with vitamin D deficiency were
      subdivided into 2 groups: one with vitamin D supplementation and the other
      without vitamin D supplementation. Further assessment and follow-up of children
      with ADHD was done. The Wisconsin Card Sorting Test, Conners' Parent Rating
      Scale, and Wechsler Intelligence Scale for Children were performed at baseline
      and follow-up in all cohorts with an ADHD diagnosis. RESULTS: The diagnosis of
      vitamin D deficiency was significantly greater in children with ADHD compared
      with the control group ( P < 0.05). Children with ADHD had significantly ( P =
      0.0009) lower values of serum vitamin D (17.23 +/- 8.98) than the control
      group(31.47 +/- 14.42). The group receiving vitamin D supplementation
      demonstrated improvement in cognitive function in the conceptual level,
      inattention, opposition, hyperactivity, and impulsivity domains. CONCLUSION:
      Vitamin D supplementation in children with ADHD may improve cognitive function.

PMID- 29457494
TI  - Management of Phenobarbital and Apixaban Interaction in Recurrent Cardioembolic
      Stroke.

PMID- 29457495
TI  - Effects of Initial Body Mass Index and Weight Change on All-Cause Mortality: A 10
      Year Cohort Study in Korea.
AB  - We evaluated the effects of baseline body mass index (BMI) and its changes over 4
      years on all-cause mortality in Korean population. We analyzed 351 735
      participants whose BMI was measured in both 2002/2003 and 2006/2007. Mortality
      was assessed until 2013. Multivariate hazard ratios for all-cause mortality were
      estimated. Underweight and severe obesity with BMI >30 kg/m2 were significantly
      associated with higher mortality. Similarly, >5% decrease or >10% increase of BMI
      for 4 years was associated with the increased risk of death. Comparing the
      results between baseline BMI and BMI change, the BMI change showed more stable
      associations with mortality than the baseline BMI in subgroup analysis such as
      nonsmokers and healthy participants. This study suggests that BMI change could be
      a useful health indicator along with obesity level by BMI. In addition,
      maintaining a healthy weight is needed for longevity, but rapid weight change
      should be carefully monitored.

PMID- 29457496
TI  - Prostate Cancer Risk Reduced by Physical Activity Even Among Men With Prolonged
      Sitting Time: A Study From Vietnam.
AB  - Increasing prostate cancer incidence in the Asia-Pacific region may be related to
      a more sedentary lifestyle resulted from economic growth and rapid urbanization.
      The present case-control study of 640 men aged 64 to 75 years was conducted in
      Vietnam between 2013 and 2015 to ascertain the relationship between physical
      activity and prostate cancer risk, accounting for the duration of sitting time.
      Reduced prostate cancer risks were found for men engaging in medium (15.8-47.3
      metabolic equivalent task [MET]-h/week) and high (>47.3 MET-h/week) physical
      activity levels, with the adjusted odds ratios being 0.52 (95% confidence
      interval = 0.35-0.77) and 0.27 (95% confidence interval = 0.14-0.49),
      respectively. This association was independent of sitting time. Analyses of joint
      association of physical activity and sitting time also found a reduction in the
      cancer risk for higher energy expenditure levels. Similar results were evident
      for both low-medium and high grade tumors. The findings are important for
      developing health strategies to prevent prostate cancer in Asian countries.

PMID- 29457497
TI  - Prevalence and Demographic Correlates of Overweight, Physical Activity, and
      Screen Time Among School-Aged Children in Urban China: The Shanghai Study.
AB  - This study reports the prevalence and demographic correlates of overweight, as
      well as meeting physical activity and screen time guidelines, in Chinese
      children. A representative sample of school-aged children ( n = 49 549) in
      Shanghai were participants. Children's anthropometrics were objectively measured;
      their physical activity and screen time, and demographic variables including age,
      sex, skill proficiency, sport affiliation, and transportation mode were self
      reported. Multivariate logistic regression analyses were conducted. The
      prevalence of overweight was 24.9%, meeting physical activity guidelines was
      20.5%, and meeting screen time guidelines was 73.5%. Boys (odds ratio [OR] =
      1.60, 95% confidence interval [CI] = 1.50-1.71) had higher overweight prevalence
      than girls. Girls (OR = 0.91, 95% CI = 0.85-0.97) and those without sport
      affiliation (OR = 0.48, 95% CI = 0.42-0.54) were less likely to meet physical
      activity recommendations than their counterparts. Girls were more likely than
      boys to meet screen time recommendations (OR = 1.29, 95% CI = 1.22-1.37).
      Children's sex, sport affiliation, and skill proficiency are factors that
      policymakers can use to improve body weight status, physical activity
      participation, and screen time.

PMID- 29457498
TI  - Factors Associated With Maternal Depression in the Maldives: A Prospective Cohort
      Study.
AB  - The aim of the study was to document perinatal depression in mothers in the
      Maldives and associated factors. A cohort of 458 mothers was recruited at the 2
      major hospitals in Male, the Maldives, and followed from 36 weeks of pregnancy to
      3 months after birth. The Edinburgh Postnatal Depression Scale (EPDS) was used to
      measure maternal depression. Maternal sociodemographic factors and infant's
      health were also recorded. The prevalence of depressive symptoms (EPDS score
      >=13) at 36 weeks of pregnancy and at 1 and 3 months postpartum were 24%, 27%,
      and 12%, respectively. Having experienced stressful life events is an established
      risk factor for maternal depression across these time points. Having depressive
      symptoms during the postpartum period is significantly associated with presence
      of antenatal depressive symptoms. Future studies may look into effectiveness of
      strategies that cope with stressors in the management of maternal depression.

PMID- 29457499
TI  - Factors Related to Alcohol Consumption Among Japanese Physicians.
AB  - This study aimed to investigate the drinking habits of Japanese physicians, and
      clarify their causal factors. A self-administered questionnaire was sent to 6000
      male and 1500 female physicians, selected from among members of the Japan Medical
      Association. We analyzed the correlation of drinking habits with age, medical
      department, smoking and exercise status, work environment, sleep problems, and
      mental health. The response rate was 79.4%. Physicians with a heavy drinking
      habit were most frequently men in their 60s and women in their 20s to 50s.
      Drinking or heavy drinking tendencies decreased with increasing age. Smoking
      status was correlated with heavy drinking. Exercise status was correlated with
      drinking among men, and drinking/heavy drinking among women. Mental health was
      not correlated with drinking habit. However, sleep problems were correlated with
      a heavy drinking habit. These results suggest that countermeasures need to be
      taken to decrease the rate of heavy drinking among physicians.

PMID- 29457505
TI  - Death after bite from severed snake head.

PMID- 29457506
TI  - New alkylamide from the stems of Zanthoxylum nitidum.
AB  - A new alkylamide, named (2E,6E,8E)-N-(2-methylpropyl)-10-oxo-2,6,8-decatrienamide
      (1), together with 22 known compounds (2-23), were isolated from the stems of
      Zanthoxylum nitidum. Their structures were elucidated by spectroscopic methods,
      including 1D and 2D NMR spectroscopy. The isolated compounds exhibited slightly
      antioxidant activities through DPPH and ABTS radical scavenging assays but showed
      no antibacterial activity against Streptococcus mutans ATCC2517, a dental caries
      causing bacteria.

PMID- 29457507
TI  - Whom Do You Trust.

PMID- 29457508
TI  - Integrative Review of Mobile Phone Contacts and Medication Adherence in Severe
      Mental Illness.
AB  - BACKGROUND: Poor medication adherence is a significant problem in individuals
      with severe mental illness (SMI). About 50% of people with SMI become nonadherent
      to treatment in the first month following discharge from the hospital. OBJECTIVE:
      This study examined literature in the past decade (2006-2016) on the use of
      mobile phone contacts in individuals with SMI to improve medication adherence
      post hospital discharge. DESIGN: This integrative review used the search terms
      texting, text messaging, SMS, cell/mobile phone, medication adherence, medication
      compliance, and mental illness. Databases (CINAHL, PubMed, PsycINFO, and Scopus)
      and manual searching of reference lists were done. The main inclusion criteria
      were the use of mobile phone contacts on medication adherence in individuals with
      SMI. Adults 18 years and older, studies conducted from 2006 to 2016, and studies
      conducted in English were also criteria for inclusion. Only five studies met
      criteria for inclusion. RESULTS: Outcomes from the review showed that mobile
      phone contacts have been used to improve medication adherence in individuals with
      SMI and able to provide the four types of social support (instrumental,
      informational, emotional, and, appraisal). When phone contacts especially text
      messaging was used as an adjunct to other interventions, it yielded better
      medication adherence than when used alone. However, results on medication
      adherence rates were mixed in participants on both psychiatric and nonpsychiatric
      medications. CONCLUSION: Although mobile phone contacts are a promising tool to
      enhance medication adherence after hospital discharge, its effectiveness to
      increase medication adherence in this population remains inconclusive.

PMID- 29457509
TI  - Evidence-based practice self-efficacy of undergraduate speech pathology students
      following training.
AB  - AIM: The aims of this study were to determine the self-efficacy of speech
      pathology students in conducting evidence-based practice before and after a
      comprehensive evidence-based practice course, and the impact of timing of the
      course (Semester 1/2). METHOD: Students attended a 13-week course in their final
      year of study. The evidence-based practice confidence scale (EPIC) was used to
      measure the students' self-efficacy pre- and post-training. RESULTS: Ninety-two
      percent of students enrolled over six semesters participated. Students began the
      evidence-based practice course with high confidence in asking patients their
      preferences but low confidence in interpreting and analysing statistics. A
      significant improvement in confidence in all evidence-based practice areas was
      found, with greatest improvement occurring in the critical appraisal of research.
      Overall, the teaching had greatest effect on a group of skills for finding valid
      EBP information. There were significant differences between semester one and two
      students in only 18% of responses. Semester two students were more confident in
      half of these responses. CONCLUSIONS: An evidence-based practice course made a
      significant difference to student self-efficacy across all aspects, with few
      differences related to timing of the course. Implications are discussed.
      Implications for Rehabilitation Health professionals must be confident
      implementing evidence-based practice throughout the course of their careers, as
      best practice changes over time. A capstone unit of study/course for
      undergraduate speech pathology students significantly improved their self
      efficacy in implementing evidence-based practice. This has positive implications
      for evidence-based practice across a wide range of clinical settings including
      rehabilitation and disability as the graduate entry level students enter the
      workforce. For on-going success, graduate entry level students must continue to
      implement evidence-based practice as clinicians if they are to maintain their
      confidence and further develop their skill set.

PMID- 29457511
TI  - A probabilistic intake model to estimate the impact of reformulation by the food
      industry among Irish consumers.
AB  - This project quantified the impact that voluntary reformulation efforts of the
      food industry had on the Irish population's nutrient intake. Nutrient composition
      data on reformulated products were collected from 14 major food companies for two
      years, 2005 and 2012. Probabilistic intake assessments were performed using the
      Irish national food consumption surveys as dietary intake data. The nutrient data
      were weighted by market shares replacing existing food composition data for these
      products. The reformulation efforts assessed, significantly reduced mean energy
      intakes by up to 12 kcal/d (adults), 15 kcal/d (teens), 19 kcal/d (children) and
      9 kcal/d (pre-schoolers). Mean daily fat intakes were reduced by up to 1.3 g/d,
      1.3 g/d, 0.9 g/d and 0.6 g/d, saturated fat intakes by up to 1.7 g/d, 2.3 g/d,
      1.8 g/d and 1 g/d, sugar intakes by up to 1 g/d, 2 g/d, 3.5 g/d and 1 g/d and
      sodium intakes by up to 0.6 g/d, 0.5 g/d, 0.2 g/d, 0.3 g/d for adults, teenagers,
      children and pre-school children, respectively. This model enables to assess the
      impact of industry reformulation amongst Irish consumers' nutrient intakes, using
      consumption, food composition and market share data.

PMID- 29457510
TI  - Hepatocellular carcinoma abutting large vessels: comparison of four percutaneous
      ablation systems.
AB  - PURPOSE: To compare overall local tumour progression (OLTP), defined as the
      failure of primary ablation or local tumour progression, with single applicator
      monopolar radiofrequency ablation (RFA), microwave ablation (MWA), cluster-RFA
      and multi-bipolar radiofrequency (mbpRFA) in the treatment of hepatocellular
      carcinoma (HCC) <= 5 cm abutting large vessels (>=3 mm). MATERIALS AND METHODS:
      This multicenter, retrospective, per-nodule study was performed from 2007 to
      2015. The study was approved by the ethics review board, and informed consent was
      waived. A total of 160/914 HCC nodules treated by thermal ablation and abutting
      large vessels (40 per treatment group) treated by monopolar RFA, MWA, cluster-RFA
      or mbpRFA were matched for tumour size, alpha-feto-protein level and vessel size.
      OLTP rates were compared by the log-rank test and the multivariate Cox model
      after matching. RESULTS: No differences were observed in tumour size, vessel size
      or alpha-feto-protein levels among the three groups (p = 1). The cumulative 4
      year OLTP rates following monopolar RFA, cluster-RFA, multi-bipolar RFA and MWA
      were 50.5%, 16.3%, 16.3% and 44.2%, respectively (p = 0.036). On multivariate Cox
      regression, vessel size >=10 mm, monopolar RFA and MWA were independent risk
      factors of OLTP compared to cluster-RFA or mbpRFA. CONCLUSION: Multi-applicator
      RFA provides better local tumour control in HCC abutting large vessels than
      single-applicator techniques (monopolar RFA or MWA).

PMID- 29457512
TI  - Perceived Diet and Exercise Behaviors Among Social Network Members With Personal
      Lifestyle Habits of Public Housing Residents.
AB  - Our objective was to characterize the relationship between public housing
      residents' diet/exercise habits with similar behaviors among their social
      network. We conducted a cross-sectional survey of randomly selected households in
      Baltimore, Maryland, from August 2014 to August 2015. Adult heads of household
      completed questions on diet, exercise, and perceived habits among network
      members. Our dependent variables were high added sugar intake (>=39.9
      teaspoons/day), high fruit/vegetable intake (>=6.1 servings/day), and being
      physically active (>=moderately activity). Our network exposures were proportion
      of members perceived to daily consume (1) sugar-sweetened beverages, (2) sweets,
      (3) fruits, and (4) vegetables, as well as to weekly exercise (1) vigorously or
      (2) moderately. We used multivariate logistic regression to examine associations
      between habits with relevant network exposures. Our sample included 266 adults
      with mean age of 44.5 years, 86.1% women and 95.5% African American. We found a
      statistically significant association between study participants' high daily
      intake of added sugar with perceived network exposure to daily sugar-sweetened
      beverages (odds ratio [OR] = 1.10, 95% confidence interval [CI] [1.02, 1.20]) and
      daily sweets (OR = 1.10, 95% CI [1.02, 1.20]). Greater network exposure to weekly
      vigorous exercise was significantly associated with personally being physically
      active (OR = 1.15, 95% CI [1.04, 1.28]), but not network exposure to weekly
      moderate exercise. Among public housing residents, associations exist between
      individuals' and perceived networks' lifestyle habits of high added sugar foods
      consumption and vigorous exercise, which may hold promise for future social
      network interventions.

PMID- 29457513
TI  - Qualifying the difficulty of embryo transfer with a visual analogue scale and
      assessing its impact on IVF outcomes.
AB  - The aim of this study was to determine whether a continuous visual analogue scale
      (VAS) is a reliable tool to grade embryo transfer (ET) difficulty when assessing
      IVF outcomes. No standardized grading system exists for reporting ET 'difficulty'
      which is typically recorded in descriptive terms. Clinicians performing 188 fresh
      single ETs between November 2014 and May 2016 also recorded a VAS score (0-100).
      Embryo transfers were stratified into three levels of ET 'difficulty': (A) 'easy'
      - no resistance; (B) 'medium' - resistance overcome by advancing the catheter's
      outer sheath; and (C) 'difficult' - a malleable stylet was required to overcome
      resistance; and these compared to the VAS scores. Clinical pregnancy and live
      birth rates were the primary outcomes. VAS scores were categorized into four
      incremental groupings according to the 25th, 50th and 75th percentiles (Groups 1
      4) for analysis. No significant relationship (p > 0.05) was seen in clinical
      pregnancy or live birth rates in either the standard difficulty or the VAS
      groupings. The median VAS scores in Groups A-C increased as difficulty increased,
      but the interquartile ranges overlap with wide clinician variation, suggesting
      the VAS is not itself a reliable enough tool to record ET difficulty in
      isolation.

PMID- 29457514
TI  - Relapse of bullous pemphigoid: an update on this stubborn clinical problem.
AB  - Bullous pemphigoid (BP) is a chronic autoimmune blistering disorder that has a
      predilection for the elderly. It is characterized by a poor prognosis due to its
      high mortality rate and the tendency to relapse. The relapse rate of BP ranges
      from 27.87% to 53% after disease remission, while the majority of relapses occur
      early (within 6 months) during remission. Clinical interventions aimed to prevent
      early relapses could reduce potential complications from first-line treatment and
      make follow-up care easier for clinicians in practice, thus improving the
      prognosis of BP and the quality of patients' lives. In this article, we attempt
      to review previous studies from the medical literature concerning relapse and
      risk factors related to relapse in BP patients. Treatments found to be able to
      reduce or increase relapse rate were also discussed. We propose that clinicians
      be aware of these risk factors and manage proper treatment accordingly. Key
      Messages   * The relapse rate of bullous pemphigoid ranges from 27.87% to 53%
      after disease remission, while the majority of relapses occur early (within 6
      months) during remission.   * Ageing, disease severity, neurological disorder,
      serum ECP, BAFF, IL-17, IL-23, CXCL10 and anti-BP180 antibody levels have been
      shown to be related to relapse, while confirmation studies are needed before
      using them for guidance for relapse prevention.   * Longer usage of
      corticosteroid with a low dose, combination of immunosuppressants and intravenous
      immunoglobulin are helpful in lowering relapse rate.

PMID- 29457515
TI  - ANTIBIOSTOP, for all?

PMID- 29457516
TI  - Effects of chocolate-based products intake on blood glucose, insulin and ghrelin
      levels and on satiety in young people: a cross-over experimental study.
AB  - This cross-over experimental study aimed to examine the effects of filled
      chocolate consumption on blood glucose, insulin and ghrelin levels in 20
      volunteers. After a one-week run-in period, study participants consumed two
      chocolate-based products, the tested biscuit or water for 21 days as a morning
      snack. After a two-week wash-out period, participants consumed another tested
      food for another 21 days. Each participant consumed all four test foods within an
      18-week period. The participants' blood insulin increased slowly after two
      chocolate-based products intakes on the first day and satiety levels after eating
      chocolate-based products and the tested biscuit were the same. Chocolate
      consumption for three weeks had no adverse effects on blood glucose, insulin or
      ghrelin levels. In conclusion, compared to eating the tested biscuit, 21-day
      consumption of the tested chocolate-based products had no adverse effects on the
      blood glucose, insulin and ghrelin levels. This trial is registered with
      chictr.org.cn: ChiCTR-IOR-16009525.

PMID- 29457517
TI  - The protection of resveratrol and its combination with glibenclamide, but not
      berberine on the diabetic hearts against reperfusion-induced arrhythmias: the
      role of myocardial KATP channel.
AB  - CONTEXT: Cardiovascular dysfunctions such as life-threatening arrhythmias are one
      of the main reasons of mortality and morbidity in diabetic patients Objective: We
      aimed to investigate the long-term effects of resveratrol, berberine and
      glibenclamide combinations on the ischemia/reperfusion (I/R) induced arrhythmias
      in streptozotocin (STZ)-induced diabetic rats and to investigate the role of
      myocardial KATP channel in the possible anti-arrhythmic actions of the
      treatments. METHODS: Two days after induction of diabetes, diabetic rats were
      treated with resveratrol [5 mg/kg, intraperitoneally (i.p.)], berberine (10
      mg/kg, i.p) and glibenclamide (5 mg/kg, i.p) for 6 weeks. On the 43th day,
      experimental animals were subjected to 6-min ischemia and 6-min reperfusion in
      vivo. RESULTS: The protein expression of Kir6.2 subunits was downregulated in the
      diabetic hearts. However, all drug treatments restored the protein expression of
      Kir6.2 subunits. Resveratrol alone and its combination with glibenclamide
      decreased the arrhythmia score, the arrhythmic period and the incidence of other
      types of arrhythmias during the reperfusion period. CONCLUSIONS: The combination
      of resveratrol with glibenclamide may alleviate reperfusion-induced arrhythmias
      via an underlying mechanism not be only associated with the restoration of the
      protein expression of Kir6.2 subunits but also associated with the other subunits
      or ion channels underlying cardiac action potential.

PMID- 29457519
TI  - Polygonatone H, a new homoisoflavanone with cytotoxicity from Polygonatum
      Cyrtonema Hua.
AB  - A new homoisoflavonoid, (3R)-5,7-dihydroxy-6-methyl-3-(2'-hydroxy-4'
      methoxybenzyl)-chroman-4-one (1), namely polygonatone H, in addition to fourteen
      known homoisoflavones (2-15) were isolated from the rhizome of Polygonatum
      Cyrtonema Hua. The structures were identified with the aid of 1D/2D NMR
      spectroscopic technologies. Compounds 2, 6, 8, 10, 11, 13, and 15 were isolated
      from P. Cyrtonema for the first time. Compound 1 showed cytotoxicities to human
      cancer cell lines with IC50 values to comparable those of cisplatin.

PMID- 29457518
TI  - Surface modification of doxorubicin-loaded nanoparticles based on polydopamine
      with pH-sensitive property for tumor targeting therapy.
AB  - One major challenge of current surface modification of nanoparticles is the
      demand for chemical reactive polymeric layers, such modification is always
      complicated, inefficient, and may lead the polymer lose the ability to
      encapsulate drug. To overcome this limitation, we adopted a pH-sensitive platform
      using polydopamine (PDA) as a way of functionalizing nanoparticles (NPs)
      surfaces. All this method needed to be just a brief incubation in weak alkaline
      solution of dopamine, which was simple and applicable to a variety of polymer
      carriers regardless of their chemical reactivity. We successfully conjugated the
      doxorubicin (DOX)-PDA-poly (lactic-co-glycolic acid) (PLGA) NPs with two typical
      surface modifiers: folate (FA) and a peptide (Arg-Gly-Asp, RGD). The DOX-PDA-FA
      NPs and DOX-PDA-RGD-NPs (targeting nanoparticles) were characterized by particle
      size, zeta potential, and surface morphology. They were quite stable in various
      physiological solutions and exhibited pH-sensitive property in drug release.
      Compared to DOX-NPs, the targeting nanoparticles possessed an excellent targeting
      ability against HeLa cells. In addition, the in vivo study demonstrated that
      targeting nanoparticles achieved a tumor inhibition rate over 70%, meanwhile
      prominently decreased the side effects of DOX and improve drug distribution in
      tumors. Our studies indicated that the DOX-PLGA-NPs modified with PDA and various
      functional ligands are promising nanocarriers for targeting tumor therapy.

PMID- 29457521
TI  - Relationships Between Race/Ethnicity and Health Care Utilization Among Older Post
      Acute Home Health Care Patients.
AB  - Few studies have explored racial/ethnic differences in health care outcomes among
      patients receiving home health care (HHC), despite known differences in other
      care settings. We conducted a retrospective cohort study examining racial/ethnic
      disparities in rehospitalization and emergency room (ER) use among post-acute
      patients served by a large northeastern HHC agency between 2013 and 2014 ( N =
      22,722). We used multivariable binomial logistic regression to describe the
      relationship between race/ethnicity and health care utilization outcomes,
      adjusting for individual-level factors that are conceptually related to health
      service use. Overall rates of rehospitalization and ER visits were 10% and 13%,
      respectively. African American and Hispanic patients experienced higher odds of
      ER visits or rehospitalization during their HHC episode. Racial/ethnic
      differences in utilization were mediated by enabling factors, such as caregiver
      availability, and illness-level factors, such as illness severity, functional
      status, and symptoms. Intervention targets may include early risk assessment,
      proactive management of clinical conditions, rehabilitative therapy, and
      caregiver training.

PMID- 29457520
TI  - Caregiver Reactions to Aggressive Behaviors in Persons With Dementia in a
      Diverse, Community-Dwelling Sample.
AB  - PURPOSE: To describe caregiver challenges with and confidence managing three
      aggressive behavior types in persons with dementia: verbal aggression, destroying
      property, and threatening to hurt others. DESIGN AND METHOD: Secondary analysis
      of baseline data from the 2001-2004 Resources for Enhancing Alzheimer's Caregiver
      Health II (REACH II) initiative. RESULTS: One or more aggressive behaviors within
      1 week were reported by more than a third of caregivers, with most expressing
      upset but fewer expressing confidence managing the behaviors. Caregiver distress
      and confidence differed by race/ethnicity in response to verbal aggression, with
      more White/Caucasian caregivers expressing upset than Hispanic/Latinos or
      Black/African Americans. Fewer Hispanic/Latinos expressed confidence managing
      verbal aggression, compared with White/Caucasians or Black/African Americans.
      DISCUSSION: Aggressive behaviors challenge caregivers, with reactions varying by
      behavior type and race/ethnicity. Cultural and contextual factors suggest the
      need to tailor interventions, especially skill-building interventions that
      increase confidence managing aggressive behaviors while decreasing upset.

PMID- 29457522
TI  - A high prevalence of TMD is related to somatic awareness and pain intensity among
      healthy dental students.
AB  - OBJECTIVE: Dental students have been identified as a group with high risks of
      developing both temporomandibular disorders (TMD) and psychosocial conditions.
      Our primary aim was to evaluate the cross-sectional prevalence of TMD diagnoses,
      as defined in the Diagnostic Criteria (DC)/TMD, among dental students. The
      secondary aim was to evaluate the prevalence and association of behavioural and
      psychosocial factors in relation to DC/TMD diagnoses. MATERIALS AND METHODS: The
      study was conducted among undergraduate dental students during the second
      semester of their third year at the Department of Odontology, Medical Faculty,
      Umea University, Sweden. Three consecutive cohorts were recruited during August
      in 2013, 2014, 2015. In total, 54 students were included and examined according
      the DC/TMD procedure. RESULTS AND CONCLUSIONS: The prevalence of any DC/TMD
      diagnosis was 30%. The most prevalent TMD diagnosis was myalgia. Individuals with
      a TMD-pain diagnosis (i.e. myalgia or arthralgia) reported significantly higher
      pain intensity levels according to the Graded Chronic Pain Scale (GCPS) as
      compared to individuals without TMD-pain (Fisher's exact test p < .001, two
      sided). In addition, individuals with any TMD scored significantly higher jaw
      functional limitations according to the Jaw Functional Limitation Scale 20 (JFLS
      20, p < .001) and oral parafunctions according to the Oral Behavior Checklist
      (OBC, p = .005) as compared to individuals without TMD. The psychosocial factors
      evaluated did not differ between individual with or without a TMD diagnosis. The
      majority of the dental students reported symptoms that are already identified as
      risk factors for developing TMD and pain conditions. However, longitudinal data
      are needed to evaluate how this evolves over time.

PMID- 29457523
TI  - Natural products for controlling hyperlipidemia: review.
AB  - Hyperlipidemia is an abnormality of lipid metabolism, characterized by an
      elevation of total cholesterol, triglyceride, and low density lipoprotein
      cholesterol, and/or a decreasing of high density lipoprotein cholesterol in
      circulating levels. Hyperlipidemia has been ranked as one of the greatest risk
      factors contributing to prevalence and severity of coronary heart diseases.
      Hyperlipidemia-associated lipid disorders are considered the cause of
      atherosclerotic cardiovascular disease. There has been a growing interest in
      natural products and their role in the maintenance and improvement of health and
      wellness. The cholesterol-lowering effect of dietary plants has been well studied
      and various natural products were shown to be helpful in lowering plasma
      cholesterol levels and encouraging safety profile. The main focus of this review
      is to describe what we know to date of natural products, along with their lipid
      lowering mechanisms, which are either through inhibition of cholesterol
      absorption, inhibition of cholesterol synthesis or antioxidant mechanisms.

PMID- 29457524
TI  - Safety and effect on ablation size of hydrochloric acid-perfused radiofrequency
      ablation in animal livers.
AB  - PURPOSE: Our objective was to determine the safety and ablation size of
      hydrochloric acid-perfused radiofrequency ablation (HCl-RFA) in liver tissues,
      prospectively using in vivo rabbit and ex vivo porcine liver models. MATERIALS
      AND METHODS: The livers in 30 rabbits were treated in vivo with perfusions of
      normal saline (controls) and HCl concentrations of 5%, 10%, 15%, and 20%, during
      RFA at 103  degrees C and 30 W for 3 min. For each experimental setting, six
      ablations were created. Safety was assessed by comparing baseline weight and
      selected laboratory values with those at 2, 7, and 14 days' post-ablation, and by
      histopathological analysis. The livers in 25 pigs were treated ex vivo with the
      same five perfusions during RFA at 103  degrees C, at both 30 W and 60 W, for 30
      min. Ablation diameters and volumes were measured by two examiners. RESULTS:
      Rabbit weights and selected laboratory values did not differ significantly from
      baseline to 7 and 14 days' post-ablation, liver tissues outside the ablation
      zones were normal histologically, and adjacent organs showed no macroscopic
      damage. The mean ablation volumes in the porcine livers treated with HCl-RFA were
      all larger than those treated with normal saline perfusion during RFA (NS-RFA),
      at both 30 W and 60 W (p < 0.001). The largest ablation volume and transverse
      diameter were observed in the porcine livers during 10% HCl-RFA at 60 W,
      measuring 179.22 (SD = 24.79) cm3 and 6.84 (SD = 0.36) cm, respectively.
      CONCLUSIONS: Based on our experiments, HCl-RFA in the liver appears to be as safe
      as NS-RFA while also resulting in larger ablation zones.

PMID- 29457525
TI  - Interleukin-1beta induces apoptosis in annulus fibrosus cells through the
      extracellular signal-regulated kinase pathway.
AB  - PURPOSE: The loss of intervertebral disc (IVD) cells due to excessive apoptosis
      induced by inflammatory cytokines is a major cause of IVD degeneration. This
      study aims to explore the mechanism of interleukin-1beta (IL-1beta)-induced
      apoptosis of annulus fibrosus cells (AFCs). It's hypothesized that IL-1beta
      induces apoptosis through the extracellular signal-regulated kinase (ERK) pathway
      in AFCs. METHODS: The mRNA and protein expression levels of apoptosis-associated
      genes were analyzed by quantitative real-time PCR and Western blotting. The
      apoptotic rate was measured by flow cytometry. Three experimental groups were
      established, including Control, IL-1beta, and IL-1beta+U0126 groups,
      respectively. RESULTS: Increase in the expression of apoptosis-associated genes
      including B-cell lymphoma-2 associated X (Bax), caspase-3, and caspase-9, and
      meanwhile, decrease in the expression of B-cell lymphoma-2 (Bcl-2) gene were
      found in patients with degenerative IVDs. In in vitro tests, both apoptosis and
      phosphorylated ERK expression in rat AFCs decreased in the IL-1beta+U0126 group
      compared with the IL-1beta group. The expression levels of Bax, caspase-3, and
      caspase-9 in AFCs decreased significantly in the IL-1beta+U0126 group compared
      with those in the IL-1beta group. The expression level of Bcl-2, on the other
      hand, significantly increased. CONCLUSIONS: Findings from this study suggest that
      IL-1beta induces apoptosis in AFCs through the ERK pathway, and therefore, ERK
      inhibition may provide certain protection against the adverse effects of IL
      1beta.

PMID- 29457526
TI  - Erratum.

PMID- 29457527
TI  - Reviewers Acknowledgments.

PMID- 29457528
TI  - Quantitative Trait Loci Influencing Hb F Levels in Southern Thai Hb E (HBB:
      c.79G>A) Heterozygotes.
AB  - Variation of fetal hemoglobin (Hb F) expression in heterozygous Hb E (HBB:
      c.79G>A) individuals is associated with several genetic modifiers and not well
      understood. This study was undertaken in order to determine the effect of single
      nucleotide polymorphisms (SNPs), including XmnI Ggamma (rs7482144), rs766432 on
      the BCL11A gene and rs9376074 on the HBS1L gene, on Hb F levels in Southern Thai
      heterozygous Hb E individuals. A total of 97 Southern Thai subjects carrying
      heterozygous Hb E were selected for the hematological study. After excluding the
      samples with alpha-thalassemia (alpha-thal) interaction or moderate anemia,
      because both conditions can affect the hematological parameters, the remaining 74
      samples were submitted to SNP analysis. Hematological parameters were measured
      using an automated hematology analyzer and high performance liquid chromatography
      (HPLC). The results show that rs766432 was strongly associated with increased Hb
      F levels and rs7482144 was associated with Hb F levels in each subgroup
      (genotype) of rs766432. This study suggested that the BCL11A locus has a major
      effect on Hb F levels compared with the XmnI polymorphism in Hb E heterozygotes.
      This association of Hb F levels with SNPs is useful for the interpretation of
      hemoglobin (Hb) typing in heterozygous Hb E samples with high Hb F levels. Future
      research will need to address the better understanding of the mechanisms of the
      SNPs that regulate Hb F production without stress erythropoiesis in Hb E
      heterozygotes.

PMID- 29457530
TI  - A new insight into the classification of dusky thrush complex: bearings on the
      phylogenetic relationships within the Turdidae.
AB  - Dusky thrush complex comprises of two sister species breeding in SC Siberia,
      which is the member of thrush Turdus from Turdidae. The phylogenetic resolution
      of Dusky thrush complex remains controversial, and a detailed research is still
      necessary. In this research, we determined the complete mtDNAs of both species,
      and estimated phylogenetic trees based on the mtDNA alignment of these and 21
      other Turdidae species, to clarify the taxa status of the Dusky thrush complex.
      The squenced lengths of these three mitochondrial genomes were 16,737, 16,788 and
      16,750 bp. The mtDNAs are circular molecules, containing the 37 typical genes,
      with an identical gene order and arrangement as those of other Turdidae. The ATG
      and TAA, respectively, are observed the most commonly start and stop codon. Most
      of the tRNA could be folded into the canonical cloverleaf secondary structure
      except for tRNASer (AGY) and tRNALeu (CUN), which lose 'DHU' arm. The control
      region presented a higher A + T content than the average value for the whole
      mitogenome. The phylogenetic trees reconstructed by the concatenated nucleotide
      sequences of mtDNA genes (Cyt b, ND2 and COI) indicate the Dusky thrush complex
      cannot be divided into two species, but the relationships between Dusky thrush
      subspecies still need additional study. This study improves our understanding of
      mitogenomic structure and evolution of the Dusky thrush complex, which can
      provide further insights into our understanding of phylogeny and taxonomy in
      Turdidae.

PMID- 29457529
TI  - N-terminal-pro-B-type-natriuretic peptide associated with 2-year mortality from
      both cardiovascular and non-cardiovascular origins in prevalent chronic
      hemodialysis patients.
AB  - N-terminal-pro-B-type-natriuretic peptide (NT-proBNP) was a predictive marker of
      cardiovascular disease (CVD)-related death in chronic dialysis patients. NT
      proBNP was also correlated with markers of inflammation, malnutrition and protein
      energy wasting. We hypothesized whether NT-proBNP was also associated with non
      CVD death in chronic dialysis patients. A prospective observational study for
      incidence of death in chronic dialysis patients was conducted. Prevalent chronic
      dialysis patients (n = 1310) were enrolled and followed for 24 months. One
      hundred forty-four deaths were recorded. Area under the curve using ROC analysis
      for NT-proBNP showed: all causes of death (0.761), CVD-related (0.750), infection
      and malignancy-related (0.702) and others and unknown (0.745). After adjusting
      for age, sex, hemodialysis vintage, cardiothoracic ratio, mean pre-dialysis
      systolic blood pressure, dry weight and basal kidney disease, the hazard ratios
      (95% confidence intervals) per 1-log NT-proBNP calculated using multivariate Cox
      analysis were: all causes of death, 3.83 (2.51-5.85); CVD-related, 4.30 (2.12
      8.75); infection and malignancy-related, 2.41 (1.17-4.93); and others and unknown
      origin, 5.63 (2.57-12.37). NT-proBNP was significantly associated not only with
      CVD-relate but also with non-CVD-related deaths in this population of prevalent
      chronic dialysis patients.

PMID- 29457531
TI  - Shedding new light on RhoA signalling as a drug target in vivo using a novel RhoA
      FRET biosensor mouse.
AB  - The small GTPase RhoA is a master regulator of signalling in cell-extracellular
      matrix interactions. RhoA signalling is critical to many cellular processes
      including migration, mechanotransduction, and is often disrupted in
      carcinogenesis. Investigating RhoA activity in a native tissue environment is
      challenging using conventional biochemical methods; we therefore developed a RhoA
      FRET biosensor mouse, employing the adaptable nature of intravital imaging to a
      variety of settings. Mechanotransduction was explored in the context of osteocyte
      processes embedded in the calvaria responding in a directional manner to
      compression stress. Further, the migration of neutrophils was examined during in
      vivo "chemotaxis" in wound response. RhoA activity was tightly regulated during
      tissue remodelling in mammary gestation, as well as during mammary and pancreatic
      carcinogenesis. Finally, pharmacological inhibition of RhoA was temporally
      resolved by the use of optical imaging windows in fully developed pancreatic and
      mammary tumours in vivo. The RhoA-FRET mouse therefore constitutes a powerful
      tool to facilitate development of new inhibitors targeting the RhoA signalling
      axis.

PMID- 29457532
TI  - Effects of real-time gait biofeedback on paretic propulsion and gait biomechanics
      in individuals post-stroke.
AB  - Objectives Gait training interventions that target paretic propulsion induce
      improvements in walking speed and function in individuals post-stroke.
      Previously, we demonstrated that able-bodied individuals increase propulsion
      unilaterally when provided real-time biofeedback targeting anterior ground
      reaction forces (AGRF). The purpose of this study was to, for the first time,
      investigate short-term effects of real-time AGRF gait biofeedback training on
      post-stroke gait. Methods Nine individuals with post-stroke hemiparesis (6
      females, age = 54 +/- 12.4 years 39.2 +/- 24.4 months post-stroke) completed
      three 6-minute training bouts on an instrumented treadmill. During training,
      visual and auditory biofeedback were provided to increase paretic AGRF during
      terminal stance. Gait biomechanics were evaluated before training, and during
      retention tests conducted 2, 15, and 30 minutes post-training. Primary dependent
      variables were paretic and non-paretic peak AGRF; secondary variables included
      paretic and non-paretic peak trailing limb angle, plantarflexor moment, and step
      length. In addition to evaluating the effects of biofeedback training on these
      dependent variables, we compared effects of a 6-minute biofeedback training bout
      to a non-biofeedback control condition. Results Compared to pre-training,
      significantly greater paretic peak AGRFs were generated during the 2, 15, and 30
      minute retention tests conducted after the 18-minute biofeedback training
      session. Biofeedback training induced no significant effects on the non-paretic
      leg. Comparison of a 6-minute biofeedback training bout with a speed-matched
      control bout without biofeedback demonstrated a main effect for training type,
      with greater peak AGRF generation during biofeedback. Discussion Our results
      suggest that AGRF biofeedback may be a feasible and promising gait training
      strategy to target propulsive deficits in individuals post-stroke.

PMID- 29457533
TI  - Pyogenic infection of the hip joint as a complication of a femoral artery
      vascular access for percutaneous coronary intervention.
AB  - A rare case of clinical complication following a percutaneous coronary
      intervention is presented. A femoral vascular access was chosen to treat a
      coronary lesion with a stent implantation. This femoral vascular access, however,
      resulted in a pyogenic infection of the ipsilateral hip joint that was not
      properly diagnosed for an extended post-interventional period. The hip joint
      completely deteriorated before its underlying cause was identified. This case
      report illustrates the importance of recognizing potential endovascular
      complications independently of their frequency.

PMID- 29457534
TI  - Comparing Hydrogels for Human Nucleus Pulposus Regeneration: Role of Osmolarity
      During Expansion.
AB  - Hydrogels can facilitate nucleus pulposus (NP) regeneration, either for clinical
      application or research into mechanisms of regeneration. However, many different
      hydrogels and culture conditions for human degenerated NP have been employed,
      making literature data difficult to compare. Therefore, we compared six different
      hydrogels of natural polymers and investigated the role of serum in the medium
      and of osmolarity during expansion or redifferentiation in an attempt to provide
      comparators for future studies. Human NP cells of Thompson grade III discs were
      cultured in alginate, agarose, fibrin, type II collagen, gelatin methacryloyl
      (gelMA), and hyaluronic acid-poly(ethylene glycol) hydrogels. Medium containing
      fetal bovine serum and a serum-free (SF) medium were compared in agarose, gelMA,
      and type II collagen hydrogels. Isolation and expansion of NP cells in low
      compared to high osmolarity medium were performed before culture in agarose and
      type II collagen hydrogels in media of varying osmolarity. NP cells in agarose
      produced the highest amounts of proteoglycans, followed by cells in type II
      collagen hydrogels. The absence of serum reduced the total amount of
      proteoglycans produced by the cells, although incorporation efficiency was higher
      in type II collagen hydrogels in the absence than in the presence of serum.
      Isolation and expansion of NP cells in high osmolarity medium improved
      proteoglycan production during culture in hydrogels, but variation in osmolarity
      during redifferentiation did not have any effect. Agarose hydrogels seem to be
      the best option for in vitro culture of human NP cells, but for clinical
      application, type II collagen hydrogels may be better because, as opposed to
      agarose, it degrades in time. Although culture in SF medium reduces the amount of
      proteoglycans produced during redifferentiation culture, isolating and expanding
      the cells in high osmolarity medium can largely compensate for this loss.

PMID- 29457535
TI  - Examining Driving and Participation 5 Years After Traumatic Brain Injury.
AB  - Participation is often considered a primary goal of traumatic brain injury (TBI)
      rehabilitation, but little is known about the influence of driving on
      participation after TBI. The objective of this study was to examine the
      independent contribution of driving status to participation at 5 years post TBI,
      after controlling for demographic, psychosocial, and functional factors.
      Participants ( N = 2,456) were community-dwelling individuals with moderate to
      severe TBI, age 18 to 65 at time of injury, and enrolled in the TBI Model Systems
      (TBIMS) National Database (NDB). Hierarchical linear regressions for the
      dependent variable of participation at 5 years post TBI were performed. Findings
      showed that driving was a highly significant independent predictor of
      participation and was a stronger relative predictor of participation than FIM(r)
      Cognitive, FIM(r) Motor, and depression. The independent contribution of driving
      to participation suggests the need to develop evidenced-based occupational
      therapy assessments and interventions that facilitate safe engagement in the
      occupation of driving to address the long-term goal of improved participation.

PMID- 29457536
TI  - Heritabilities and genetic trends for elbow score as recorded by the New Zealand
      Veterinary Association Elbow Dysplasia Scheme (1992-2013) in four breeds of dog.
AB  - AIM: To estimate the heritability of the New Zealand Veterinary Association
      (NZVA) elbow phenotype, obtain estimated breeding values (EBV) for the worst
      elbow score and estimate the genetic trends for this trait in four populous
      breeds of dogs, using the records from the NZVA Canine Elbow Dysplasia Scheme
      database (1992-2013). METHODS: Overall, 4,070 elbow records from a pedigree of
      11,311 dogs were available for animals scored between 1992 and 2013. The worst
      elbow score between the left and right elbows was identified for each dog and
      used for EBV analysis. Estimates of heritability and EBV for the elbow score of
      dogs from German Shepherd dog, Labrador Retriever, Golden Retriever and
      Rottweiler breeds were obtained using restricted maximum likelihood procedures
      with a within-breed linear animal model. The model included the fixed effects of
      sex and birth year, with age at scoring as a covariable, and the random effect of
      animal. Genetic trends for the worst-elbow score were calculated as the
      regression coefficient of the EBV, weighted by reliabilities, on year of birth.
      RESULTS: The estimates of heritability for worst-elbow score were 0.25 (SE 0.06)
      in German Shepherd dogs, 0.46 (SE 0.06) in Labrador Retrievers, 0.18 (SE 0.07) in
      Golden Retrievers and 0.29 (SE 0.11) in Rottweilers. The genetic trend for German
      Shepherd dogs was -0.0082 (SE 0.0015), for Labrador Retrievers was -0.0016 (SE
      0.0016), for Golden Retrievers was -0.0033 (SE 0.0010) and for Rottweilers was 
      0.0070 (SE 0.0023) units per annum, which were different from zero (p<0.01) in
      all breeds except Labrador Retrievers. CONCLUSIONS AND CLINICAL RELEVANCE: A
      small but favourable response to selection was achieved by three of the four
      breeds in the study period; during which selection for elbow traits has been
      largely voluntary. While the magnitude of genetic change in terms of elbow units
      per annum may appear small, it must be remembered that elbow scoring grades only
      range from 0-3. Greater improvement may be possible if compulsory screening was a
      requirement for pedigree breeding stock, and if greater selection pressure were
      applied on the basis on an individual's EBV, rather than the worst-elbow score
      alone. The maintenance of an open registry, with transparency of EBV information
      made available to all breeders, may enhance selection intensity opportunities and
      potentially assist with the process and progress of breeding selection.

PMID- 29457538
TI  - Effects of dexmedetomidine infusion during spinal anesthesia on hemodynamics and
      sedation.
AB  - BACKGROUND: We evaluated the effects of intravenous dexmedetomidine during spinal
      anesthesia on hemodynamics, respiratory rate, oxygen saturation, sedpain, and
      compared them with those of saline infusion. Sixty American Society of
      Anesthesiologists physical status I and II cases were randomly divided into two
      groups. Patients were connected to the monitor after premedication, and spinal
      anesthesia was administered. Sensory and motor blockades were assessed using
      pinprick test and Bromage scale, respectively. Group I received dexmedetomidine
      infusion and Group II received saline infusion. Throughout the infusion process,
      hemodynamic data, respiratory rate, oxygen saturation, sedation, pain, Bromage
      score, amnesia, bispectral index, and side effects were recorded. Postoperative
      hemodynamic measurements, oxygen saturation, sedation, pain scores were obtained.
      Sedation and pain were evaluated using the Ramsay and visual analog scales,
      respectively. Analgesics were administered in cases with high scores on the
      visual analog scale. Postoperative analgesic consumption, side effects,
      treatments were recorded. No significant differences were found between the
      groups with respect to oxygen saturation, respiratory rate, pain, and side
      effects in the intraoperative period. Time to onset of sensorial block, maximum
      sensorial block, onset of motor block, and maximum motor block; bispectral index
      values; and apex heartbeat until 80 min of infusion, systolic arterial blood
      pressure until 90 min, and diastolic arterial blood pressure until 50 min were
      lower, whereas amnesia and sedation levels were higher in dexmedetomidine group.
      Postoperative pain and analgesic requirement were not different. Apex heartbeat
      at 15 min and systolic arterial blood pressure at 30 min were lower and sedation
      scores were higher in the dexmedetomidine infusion group. We demonstrated
      dexmedetomidine infusion had a hemodynamic depressant effect intraoperatively
      whereas it had no significant effect on peripheral oxygen saturation, respiratory
      rate, visual analog scale scores, and side effects. Dexmedetomidine infusion
      enhanced motor and sensory blockade quality and induced amnesia and sedation.

PMID- 29457537
TI  - Effects of Binaural Spatialization in Wireless Microphone Systems for Hearing
      Aids on Normal-Hearing and Hearing-Impaired Listeners.
AB  - Little is known about the perception of artificial spatial hearing by hearing
      impaired subjects. The purpose of this study was to investigate how listeners
      with hearing disorders perceived the effect of a spatialization feature designed
      for wireless microphone systems. Forty listeners took part in the experiments.
      They were arranged in four groups: normal-hearing, moderate, severe, and profound
      hearing loss. Their performance in terms of speech understanding and speaker
      localization was assessed with diotic and binaural stimuli. The results of the
      speech intelligibility experiment revealed that the subjects presenting a
      moderate or severe hearing impairment better understood speech with the
      spatialization feature. Thus, it was demonstrated that the conventional diotic
      binaural summation operated by current wireless systems can be transformed to
      reproduce the spatial cues required to localize the speaker, without any loss of
      intelligibility. The speaker localization experiment showed that a majority of
      the hearing-impaired listeners had similar performance with natural and
      artificial spatial hearing, contrary to the normal-hearing listeners. This
      suggests that certain subjects with hearing impairment preserve their
      localization abilities with approximated generic head-related transfer functions
      in the frontal horizontal plane.

PMID- 29457539
TI  - Vocalization development in common marmosets for neurodegenerative translational
      modeling.
AB  - Objectives In order to facilitate the study of vocalizations in emerging genetic
      common marmoset models of neurodegenerative disorders, we aimed to analyze call
      type changes across age in a translational research environment. We hypothesized
      that acoustic parameters of vocalizations would change with age, reflecting
      growth of the vocal apparatus and a maturation of control needed to make adult
      like calls. Methods Nineteen developing common marmosets were longitudinally
      video- and audio-recorded between the ages of 1-149 days in a naturalistic
      setting without any vocalization elicitation protocol. Vocalizations were coded
      for call type (cry, tsik, trill, phee, and trill-phee) and analyzed for duration
      (sec), minimum and maximum frequency (Hz), and bandwidth (Hz). Mixed model linear
      regressions were performed to assess the effects of age on call parameters listed
      above for each call type. Results Cries decreased in duration (P = 0.038),
      maximum frequency (P = 0.047), and bandwidth (P = 0.023) with age. Tsik calls
      decreased in duration (P = 0.002) and increased in minimum frequency (P = 0.004)
      and maximum frequency (P = 0.005) with age. Trill calls increased in duration (P
      = 0.003), and trillphee bandwidth (P = 0.031) decreased with age. Discussion Our
      results demonstrate that development of common marmoset vocalizations is call
      type dependent and that changes in acoustic parameters can be detected without
      complex vocalization elicitation paradigms or specialized audio recording
      equipment. Thus, we demonstrate the feasibility of a naturalistic protocol to
      collect and objectively analyze marmoset vocalizations longitudinally. This
      approach may be useful for studying vocal communication deficits in genetic
      models of neurodegenerative disorders.

PMID- 29457540
TI  - Therapeutic efficacy of CD34+ cell-involved mononuclear cell therapy for no
      option critical limb ischemia: A meta-analysis of randomized controlled clinical
      trials.
AB  - Early-phase clinical trials in patients with critical limb ischemia (CLI) have
      shown positive results of mononuclear cell therapy. The current meta-analysis
      investigated whether cluster of differentiation (CD) 34+ mononuclear cell therapy
      (CD34+MCT) is effective for no-option CLI. Ten randomized controlled clinical
      studies of CD34+MCT for no-option CLI with 479 patients were identified and
      analyzed for pooled results. Compared to control groups, the CD34+MCT was
      associated with lower total amputation (odds ratio (OR): 0.45, p=0.01; 95%
      confidence interval (CI): 0.24-0.85) and a higher complete ulcer healing rate
      (OR: 2.80, p=0.008; 95% CI: 1.31-6.02), but showed no advantage in major
      amputation (OR: 0.58, p=0.11; 95% CI: 0.29-1.14) and all-cause mortality (OR:
      0.82, p=0.62; 95% CI: 0.36-1.83) . Studies with a high CD34+ cell dosage showed
      significant results in major amputation (OR: 0.38, p=0.002; 95% CI: 0.21-0.70),
      total amputation (OR: 0.31, p=0.0002; 95% CI: 0.17-0.57) and complete ulcer
      healing (OR: 7.58, p=0.0005; 95% CI: 2.40-23.88), which were not observed in the
      low-dose studies. However, inclusion of placebo-controlled studies showed no
      improvement of the CD34+MCT in total amputation (OR: 0.67, p=0.42; 95% CI: 0.25
      1.79), major amputation (OR: 1.31, p=0.43; 95% CI: 0.67-2.54) or complete ulcer
      healing (OR: 1.52, p=0.27; 95% CI: 0.72-3.21), which were extremely significant
      in non-placebo-controlled studies ( p<0.001). In conclusion, the significant
      results of CD34+MCT might not support its therapeutic benefit due to high placebo
      effect risk and considerable heterogeneity caused by distinct cell doses. More
      sizable double-blinded, randomized, placebo-controlled trials with higher CD34+
      cell dosage are needed in the future.

PMID- 29457541
TI  - Can implicit measures detect source information in crime-related amnesia?
AB  - Participants who are asked to simulate amnesia for a mock crime have a weaker
      memory for this event when they have to give up their role as a feigner, than
      those who are not asked to feign memory loss. According to the source monitoring
      framework (SMF), this memory-undermining effect of simulating amnesia for a crime
      would be due to misattribution of the right source of information. However, we
      know that the content of self-generated information (e.g., feigned version of the
      crime) might be preserved and recognised over time as a result of elaborative
      cognitive processing. In the present study, we aimed to contrast these two
      explanations. We showed participants a mock crime video and we instructed them to
      either feign amnesia (simulators) or confess the mock crime (confessors). Next, a
      free recall memory test was administered. After one week, participants were asked
      to perform a personalised source monitoring task using the autobiographical
      Implicit Association Test (aIAT). As predicted, we found that simulators were
      able to discriminate the content of their self-generated feigned story of the
      crime from the original version. Moreover, simulators were quicker than
      confessors at the aIAT task. Practical and theoretical implications of our
      results are discussed.

PMID- 29457542
TI  - Exometabolomic Profiling of Bacterial Strains as Cultivated Using Arabidopsis
      Root Extract as the Sole Carbon Source.
AB  - The ability of microorganisms to use root-derived metabolites as growth
      substrates is a key trait for success in the rhizospheric niche. However, few
      studies describe which specific metabolites are consumed or to what degree
      microbial strains differ in their substrate consumption patterns. Here, we
      present a liquid chromatography-mass spectrometry (MS) exometabolomic study of
      three bacterial strains cultivated using either glucose or Arabidopsis thaliana
      root extract as the sole carbon source. Two of the strains were previously
      isolated from field-grown Arabidopsis roots, the other is Escherichia coli,
      included as a comparison. When cultivated on root extract, a set of 62 MS
      features were commonly taken up by all three strains, with m/z values matching
      components of central metabolism (including amino acids and purine or pyrimidine
      derivatives). Escherichia coli took up very few MS features outside this commonly
      consumed set, whereas the root-inhabiting strains took up a much larger number of
      MS features, many with m/z values matching plant-specific metabolites. These
      measurements define the metabolic niche that each strain potentially occupies in
      the rhizosphere. Furthermore, we document many MS features released by these
      strains that could play roles in cross-feeding, antibiosis, or signaling. We
      present our methodological approach as a foundation for future studies of
      rhizosphere exometabolomics.

PMID- 29457543
TI  - Greener chemicals for the future: QSAR modelling of the PBT index using ETA
      descriptors.
AB  - Persistent, bioaccumulative and toxic (PBT) chemicals symbolize a group of
      substances that are not easily degraded; instead, they accumulate in different
      organisms and exhibit an acute or chronic toxicity. The limited empirical data on
      PBT chemicals, the high cost of testing together with the regulatory constraints
      and the international push for reduced animal testing motivate a greater reliance
      on predictive computational methods like quantitative structure-activity
      relationship (QSAR) models in PBT assessment. Papa and Gramatica have recently
      proposed a PBT index that could be computed directly from structural features. In
      the current study, we have modelled the experimentally derived PBT index data
      using an extended topological atom (ETA) along with constitutional descriptors to
      show the usefulness of the ETA indices in modelling the endpoint. The models
      developed through a double cross-validation (DCV) method gave the best results in
      terms of both internal and external validation metrics. The developed models were
      comparable in predictive quality to those previously reported. The current models
      were further used for consensus predictions of PBT behaviour for a set of
      pharmaceuticals and a set of synthetic drug-like compounds. The developed models
      can be used in PBT hazard screening for identification and prioritization of
      chemicals from the structural information alone.

PMID- 29457544
TI  - Mesoscale organization of domains in the plasma membrane - beyond the lipid raft.
AB  - The plasma membrane is compartmentalized into several distinct regions or
      domains, which show a broad diversity in both size and lifetime. The segregation
      of lipids and membrane proteins is thought to be driven by the lipid composition
      itself, lipid-protein interactions and diffusional barriers. With regards to the
      lipid composition, the immiscibility of certain classes of lipids underlies the
      "lipid raft" concept of plasmalemmal compartmentalization. Historically, lipid
      rafts have been described as cholesterol and (glyco)sphingolipid-rich regions of
      the plasma membrane that exist as a liquid-ordered phase that are resistant to
      extraction with non-ionic detergents. Over the years the interest in lipid rafts
      grew as did the challenges with studying these nanodomains. The term lipid raft
      has fallen out of favor with many scientists and instead the terms "membrane
      raft" or "membrane nanodomain" are preferred as they connote the heterogeneity
      and dynamic nature of the lipid-protein assemblies. In this article, we will
      discuss the classical lipid raft hypothesis and its limitations. This review will
      also discuss alternative models of lipid-protein interactions, annular lipid
      shells, and larger membrane clusters. We will also discuss the mesoscale
      organization of plasmalemmal domains including visible structures such as
      clathrin-coated pits and caveolae.

PMID- 29457550
TI  - miR-505-3p controls chemokine receptor up-regulation in macrophages: role in
      familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) conveys a high risk of premature
      atherosclerosis as a result of lifelong exposure to high LDL cholesterol levels
      that are not fully reduced by standard-of-care lipid-lowering treatment.
      Inflammatory mediators have played a role in the progression of atherosclerotic
      lesions. Here, we investigated whether innate immunity cells in patients with FH
      have a specific proinflammatory phenotype that is distinct from that of cells in
      normal participants. To this end, miR-505-3p-a microRNA related to chronic
      inflammation-and its target genes were investigated in monocyte-derived
      macrophages (MACs) of patients with FH (FH-MACs) and non-FH controls (co-MACs).
      On the basis of the profiler PCR array analysis of agomiR-505-3p-transfected
      MACs, we identified the chemokine receptors, CCR3, CCR4, and CXCR1, as genes that
      are regulated by miR-505-3p via the transcription factor, RUNX1. miR-505-3p was
      significantly down-regulated, whereas CCR3, CCR4, CXCR, and RUNX1 were increased
      in FH-MAC compared with co-MAC, with the increase being more evident in the
      proinflammatory M1-like FH-MAC. Chemokine receptor levels were unrelated to LDL
      plasma levels at entry, but correlated with age in patients with FH, not in
      controls. In summary, we demonstrate for first time to our knowledge that MACs
      from FH-MACs have an inflammatory phenotype that is characterized by the up
      regulation of CCR3, CCR4, and CXCR1 under the control of miR-505-3p. These
      results suggest a chronic inflammatory condition in FH innate immunity cells that
      is not reverted by standard lipid-lowering treatment.-Escate, R., Mata, P.,
      Cepeda, J. M., Padro, T., Badimon, L. miR-505-3p controls chemokine receptor up
      regulation in macrophages: role in familial hypercholesterolemia.

PMID- 29457551
TI  - Alternative Genetics.

PMID- 29457552
TI  - Reciprocal regulation of YAP/TAZ by the Hippo pathway and the Small GTPase
      pathway.
AB  - Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding
      motif (TAZ) (YAP/TAZ) are transcriptional coactivators that regulate genes
      involved in proliferation and transformation by interacting with DNA-binding
      transcription factors. Remarkably, YAP/TAZ are essential for cancer initiation or
      growth of most solid tumors. Their activation induces cancer stem cell
      attributes, proliferation, and metastasis. The oncogenic activity of YAP/TAZ is
      inhibited by the Hippo cascade, an evolutionarily conserved pathway that is
      governed by two kinases, mammalian Ste20-like kinases 1/2 (MST1/2) and Large
      tumor suppressor kinase 1/2 (LATS1/2), corresponding to Drosophila's Hippo (Hpo)
      and Warts (Wts), respectively. One of the most influential aspects of YAP/TAZ
      biology is that these factors are transducers of cell structural features,
      including polarity, shape, and cytoskeletal organization. In turn, these features
      are intimately related to the cell's ability to attach to other cells and to the
      surrounding extracellular matrix (ECM), and are also influenced by the cell's
      microenvironment. Thus, YAP/TAZ respond to changes that occur at the level of
      whole tissues. Notably, small GTPases act as master organizers of the actin
      cytoskeleton. Recent studies provided convincing genetic evidence that small
      GTPase signaling pathways activate YAP/TAZ, while the Hippo pathway inhibits
      them. Biochemical studies showed that small GTPases facilitate the YAP-Tea domain
      transcription factor (TEAD) interaction by inhibiting YAP phosphorylation in
      response to serum stimulation, while the Hippo pathway facilitates the YAP-RUNX3
      interaction by increasing YAP phosphorylation. Therefore, small GTPase pathways
      activate YAP/TAZ by switching its DNA-binding transcription factors. In this
      review, we summarize the relationship between the Hippo pathway and small GTPase
      pathways in the regulation of YAP/TAZ.

PMID- 29457553
TI  - The difficulty of articulatory complexity.
AB  - In our commentary, we offer some support for the view that frequency rather than
      a language-independent definition of complexity is a main factor determining
      speech production in healthy adults. We further discuss the limits of defining
      articulatory complexity based on transcription data. If we want to gauge the
      impact of substantive constraints on speech production, context-specific
      production dynamics should be considered, as has been underscored by articulatory
      acoustic work on speech errors.

PMID- 29457554
TI  - Complexity of articulation planning in apraxia of speech: The limits of phoneme
      based approaches.
AB  - This report presents evidence suggesting that the phoneme-based approach taken by
      Romani, Galuzzi, Guariglia, and Goslin (Comparing phoneme frequency, age of
      acquisition, and loss in aphasia: Implications for phonological universals.
      Cognitive Neuropsychology, this issue) falls short of capturing the complexity of
      articulation planning in patients with apraxia of speech. Empirical and modelling
      data are reported to demonstrate that the apraxic pathomechanism resides in the
      hierarchical architecture of phonological words rather than in the context
      independent properties of phonemes. Because the factors determining complexity of
      articulation planning are interlaced between gestural, syllabic, and metrical
      levels, they cannot be captured by markedness rankings limited to any of these
      levels.

PMID- 29457555
TI  - Encoding of distributional regularities independent of markedness: Evidence from
      unimpaired speakers.
AB  - Romani, Galuzzi, Guariglia, and Goslin (Comparing phoneme frequency, age of
      acquisition and loss in aphasia: Implications for phonological universals.
      Cognitive Neuropsychology) used speech error data from individuals with acquired
      impairments to argue that independent from articulatory complexity, within
      language distributional regularities influence the processing of sound structure
      in speech production. Converging evidence from unimpaired speakers is reviewed,
      focusing on speech errors in language production. Future research should examine
      how articulatory and frequency factors are integrated in language processing.

PMID- 29457556
TI  - Is markedness a confused concept?
AB  - It is well known that, across languages, certain phonological features are more
      frequent than others. But whether these facts reflect abstract universal
      markedness constraints or functional pressures (auditory and articulatory
      difficulties and lexical frequency) is unknown. Romani, Galuzzi, Guariglia, and
      Goslin (2017) report that the putative markedness of phonological features
      captures their order of acquisition and their propensity to elicit errors in
      patients with an apraxia of speech (but not in phonological aphasia). The authors
      believe these results challenge the existence of abstract markedness constraints.
      They also raise some concerns about the explanatory utility of the markedness
      hypothesis. This commentary demonstrates that markedness is not inherently vague
      or vacuous nor is it falsified by Romani et al.'s empirical findings. As such,
      these results leave wide open the possibility that some phonological markedness
      constraints are abstract.

PMID- 29457557
TI  - Complexity in articulatory and segmental levels of production.

PMID- 29457558
TI  - Theoretical and methodological issues for twenty-first century cognitive
      neuropsychology.

PMID- 29457559
TI  - Functional outcomes of inpatient rehabilitation in very elderly patients with
      stroke: differences across three age groups.
AB  - Background As the population continues to age rapidly, clarifying the factors
      affecting the prognosis in very elderly stroke patients is essential to enhance
      the quality of their rehabilitation. Objectives To compare the functional
      recovery of elderly stroke patients classified into three age groups and to
      identify the predictors of functional recovery in the very elderly following
      acute inpatient rehabilitation. Methods Observational study: We collected data on
      461 stroke patients in the neurology and neurosurgery ward and classified them
      into three age groups (65-74, 75-84, and >= 85 years). Functional recovery was
      compared among groups using the functional independence measure (FIM) at
      discharge and ADL recovery rate was compared using the Montebello rehabilitation
      factor score (MRFS). Multiple regression analysis was used to identify and
      compare the factors associated with functional recovery in each age group.
      Results Functional recovery in the >= 85 years group was lower than that in other
      age groups. Factors associated with activities of daily living (ADL) status (FIM
      at discharge) in the >= 85 years group were premorbid dependence (beta = -0.183,
      p = 0.011), motor paralysis (beta = -0.238, p = 0.001), and cognitive function
      (beta = 0.586, p < 0.001). Furthermore, the impact of cognitive function grew as
      age increased. Factors associated with ADL recovery rates (MRFS) in the >= 85
      years group were non-paretic limb function (beta = -0.294, p = 0.004) and
      cognitive function (beta = 0.201, p = 0.047). Conclusions This study identified
      the factors associated with functional recovery among very elderly stroke
      patients. Effective forms of rehabilitation for very elderly stroke patients that
      take these factors into consideration need to be investigated.

PMID- 29457560
TI  - Prophylactic intra-aortic balloon counterpulsation before surgical myocardial
      revascularization in patients with acute myocardial infarction.
AB  - INTRODUCTION: Prophylactic intra-aortic balloon counterpulsation (pIABC) is
      recommended for high-risk patients undergoing coronary artery bypass grafting
      (CABG) surgery. Criteria for high-risk patients benefiting from pIABC are
      unclear. This study aimed to specifically describe the effect of pIABC on
      outcomes of patients with acute myocardial infarction (AMI) undergoing CABG.
      METHODS: In 178 of 484 AMI patients (non-ST-segment elevation myocardial
      infarction [NSTEMI] or ST-segment elevation myocardial infarction [STEMI] <=5
      days before surgery) without cardiogenic shock who underwent CABG between 2008
      and 2013, pIABC was initiated preoperatively. After propensity score matching,
      the outcomes of 400 patients were analyzed (pIABC: 150; Control: 250). RESULTS:
      After propensity score matching, baseline and operative characteristics were
      balanced between the groups except for a higher rate of patients with a left
      ventricular ejection fraction (LVEF)<=30% in the pIABC group (26% vs. Control:
      13%; p=0.032). Seven point two percent (7.2%) of the control patients received an
      IABP intraoperatively or postoperatively. Postoperative extracorporeal life
      support (ECLS) was only needed in the control group (1.2% vs. 0%; p=0.01).
      Postoperative plasma curves of troponin I, creatine kinase (CK) and creatine
      kinase isoform MB (CK-MB) levels were reduced in the pIABC group compared with
      the control group. In-hospital mortality was reduced in the pIABC group (3.3% vs.
      control: 6.4%; p=0.18). After multivariate adjustment for other preoperative risk
      factors, pIABC was significantly protective concerning in-hospital mortality (HR
      0.56; 95%-CI 0.023-0.74; p=0.021). Mortality (pIABC vs. control) was more
      affected in patients with preoperative LVEF<=30% (2/36 (5.6%) vs. 6/31 (19%);
      heart rate (HR) 0.25; 95%-CI 0.046-1.3; p=0.13) compared with LVEF>30% (3/114
      (2.6%) vs. 10/219 (4.6%); HR 0.56; 95%-CI 0.15-2.1; p=0.55). Long-term survival
      did not differ between the groups. CONCLUSIONS: pIABC in CABG for AMI is
      associated with reduced perioperative cardiac injury and in-hospital mortality.
      Long-term survival is not affected.

PMID- 29457561
TI  - Psoriasis in the perspective of predictive, preventive participatory and
      personalized medicine.

PMID- 29457562
TI  - Quality of life outcomes in cochlear implantation of children with profound and
      multiple learning disability.
AB  - This study was performed to investigate the effect of cochlear implantation on
      the Quality of Life (QoL) of children with profound and multiple learning
      disability (PMLD). This cohort of children has been viewed historically as poor
      candidates for cochlear implantation as they generally have poor speech and
      hearing outcomes. The Irish National Cochlear Implant Program's prospectively
      maintained database was examined for all children implanted from July 1996 to
      July 2015. All charts of the 381 children implanted during this time were
      reviewed retrospectively; 16 children met criteria for being PMLD. For this
      cohort of patients, speech and hearing performance and the Glasgow Children's
      Benefit Inventory scores were retrospectively analyzed. Speech and hearing
      outcomes, as measured by Categories of Auditory Performance (CAP) and Speech
      Intelligibility Rating (SIR) scores, demonstrated little or no improvement from
      pre-implantation to an interval 3 years post-op; however, 11 out of 16 parents
      reported an improvement in their child's quality of life after implantation with
      3 out of 16 reporting no improvement. This study suggests that despite children
      with PMLD performing poorly on traditional outcome measures such as CAP and SIR
      they may have improvement to their QoL after cochlear implantation. Further study
      is warranted to characterize the impact of CI on these children.

PMID- 29457563
TI  - Novel use of the Cochlear(r) Hybrid CI24REH cochlear implant.
AB  - Cochlear implantation is becoming more widespread. From its early days to date,
      huge strides have been made in the technology and surgical technique. However,
      one challenge remains: implanting malformed or abnormal cochleae. Even more
      challenging is a cochlea that appears normal at first glance, but is not. We
      present a case of a child with chondrodysplasia punctata, who had apparently
      morphologically normal inner ears, but with one major obstacle: the cochlea was
      smaller than normal in all dimensions. To the best of our knowledge, this is the
      first case described, and the solution is a novel one as well.

PMID- 29457564
TI  - Investigating Speech Recognition and listening effort with different device
      configurations in adult cochlear implant users.
AB  - OBJECTIVES: The purpose of this study was to investigate speech recognition in
      noise and listening effort among a group of adults with cochlear implants (CIs).
      Two main research questions were addressed. First, what are the effects of omni
      versus directional microphone configuration on speech recognition and listening
      effort for noisy conditions? Second, what is the effect of unilateral versus
      bimodal or bilateral CI listening on speech recognition and listening effort in
      noisy conditions? DESIGN: Sixteen adults (mean age 58 years) with CIs
      participated. Listening effort was measured using a dual-task paradigm and also
      using a self-reported rating of difficulty scale. In the dual-task measure,
      participants were asked to repeat monosyllabic words while at the same time press
      a button in response to a visual stimulus. Participants were tested in two
      baseline conditions (speech perception alone and visual task alone) and in the
      following experimental conditions: (1) quiet with an omnidirectional microphone,
      (2) noise with an omnidirectional microphone, (3) noise with a directional
      microphone, and (4) noise with a directional microphone and with a second sided
      CI or hearing aid. When present, the noise was fixed with a +5 dB signal-to-noise
      ratio. After each listening condition, the participants rated the degree of
      listening difficulty. RESULTS: Changing the microphone from omni to directional
      mode significantly enhanced speech recognition in noise performance. There were
      no significant changes in speech recognition between the unilateral and
      bimodal/bilateral CI listening conditions. Listening effort, as measured by
      reaction time, increased significantly between the baseline and omnidirectional
      quiet listening condition though did not change significantly across the
      remaining listening conditions. Self-perceived listening effort revealed a
      greater effort for the noisy conditions, and reduced effort with the move from an
      omni to a directional microphone. CONCLUSIONS: Directional microphones
      significantly improve speech in noise recognition over omnidirectional
      microphones and allowed for decreased self-perceived listening effort. The dual
      task used in this study failed to show any differences in listening effort across
      the experimental conditions and may not be sensitive enough to detect changes in
      listening effort.

PMID- 29457565
TI  - Current Status and Future Perspectives in Canine Oral Squamous Cell Carcinoma.

PMID- 29457566
TI  - Using Genetically Modified Rodent Models in Drug Development to Explore Target
      Physiology and Potential Drug Effects.

PMID- 29457568
TI  - Editorial: Oncolytic Virus and Gene Thearapy Application: Update 2018.

PMID- 29457567
TI  - Time to Standardize? Time to Validate?

PMID- 29457569
TI  - Hospital-Onset MRSA Bacteremia Rates Are Significantly Correlated With
      Sociodemographic Factors: A Step Toward Risk Adjustment.
AB  - The correlations between census-derived sociodemographic variables and hospital
      onset methicillin-resistant Staphylococcus aureus bacteremia (HO-MRSAB) rates
      were examined at the US state level. On multivariable analysis, only percent
      African American remained statistically significant. This finding highlights an
      important disparity and suggests that risk adjustment is needed when comparing HO
      MRSAB rates among US states. Infect Control Hosp Epidemiol 2018;39:479-481.

PMID- 29457570
TI  - Infant formulae supplemented with prebiotics: Are they better than unsupplemented
      formulae? An updated systematic review.
AB  - In 2011, the Committee on Nutrition of the European Society for Paediatric
      Gastroenterology, Hepatology and Nutrition systematically reviewed published
      evidence related to the safety and health effects of the administration of
      formulae supplemented with pro- and/or prebiotics compared with unsupplemented
      formulae. We updated evidence on the effects of the administration of prebiotic
      supplemented infant formulae (IF) compared with unsupplemented IF. Five databases
      were searched up to March 2017 for randomised controlled trials. In all, forty
      one publications were identified, including twenty-five new publications. The
      administration of currently evaluated prebiotic-supplemented formulae to healthy
      infants does not raise safety concerns with regard to growth and adverse effects.
      Some favourable clinical effects are possible, primarily stool softening, which
      may be beneficial in some infants. Currently, there is no existing robust
      evidence to recommend the routine use of prebiotic-supplemented formulae. The
      latter conclusion may reflect the small amount of data on specific prebiotics and
      outcomes, rather than a genuine lack of an effect. The efficacy and safety should
      be considered for each prebiotic(s)-supplemented formula.

PMID- 29457571
TI  - A LONGITUDINAL ANALYSIS OF INTERNAL MIGRATION, DIVORCE AND WELL-BEING IN CHINA.

PMID- 29457572
TI  - Early effects on the intestinal barrier and pancreatic function after enteral
      stimulation with protease or kidney bean lectin in neonatal rats.
AB  - Gut maturation naturally accelerates at weaning in altricial mammalian species,
      such as the rat. Mimicking this, gut development can also be induced
      precociously, 3-4 d earlier than it would occur naturally, by enteral exposure to
      phytohaemagglutinin (PHA), or various proteases. We investigated the early
      effects of gut provocation on intestinal barrier and pancreatic functions, to get
      a better understanding of the mechanisms that initiate gut maturation. The
      effects of oral administration of protease (trypsin) or PHA to 14-d-old suckling
      rats were studied during 24 h in comparison with water-fed controls. Intestinal
      in vivo permeability was assessed by oral administration of different-sized
      marker molecules and measuring their passage into the blood or urine 3 h later. A
      period of 24 h following oral administration, both PHA and protease provocation
      stimulated small intestinal (SI) growth and pancreatic secretion, as indicated by
      decreased pancreatic trypsin and increased luminal enzyme content. Within 1 h of
      oral administration, both treatments prevented the absorption of macromolecules
      to blood that was observed in controls. PHA treatment hindered the passage of
      fluorescein isothiocyanate-dextran (FD) 4 to blood, whereas protease treatment
      temporarily increased plasma levels of FD4, and the urine lactulose:mannitol
      ratio, indicating increased intestinal leakiness. Following protease treatment,
      fluorescence microscopy showed decreased vesicular uptake of FD70 in the proximal
      SI and increased epithelial fluorescence in the distal SI. In conclusion, PHA and
      protease differed in their early effects on the intestinal barrier; both exerted
      a blocking effect on epithelial endocytosis, whereas protease treatment alone
      temporarily increased epithelial leakiness, which seemed to be confined to the
      distal SI.

PMID- 29457573
TI  - The role of sublexical variables in reading fluency development among Spanish
      children.
AB  - Several studies have found that, after repeated exposure to new words, children
      form orthographic representations that allow them to read those words faster and
      more fluently. However, these studies did not take into account variables related
      to the words. The aim of this study was to investigate the influence of
      sublexical variables on the formation of orthographic representations of words by
      Spanish children. The first experiment used pseudo-words of varying syllabic
      structure and syllabic frequency. The stimuli for the second experiment were
      formed with or without context-dependent graphemes. We found that formation of
      orthographic representations was influenced by syllabic structure (easier for
      words with simple syllabic structure) and the context-dependency of graphemes
      (easier in the absence of context-dependent graphemes), but not syllabic
      frequency. These results indicate that the easier it is to read a word, the
      easier it is to form an orthographic representation of it.

PMID- 29457574
TI  - Motherese, affect, and vocabulary development: dyadic communicative interactions
      in infants and toddlers.
AB  - Responsive parental communication during an infant's first year has been
      positively associated with later language outcomes. This study explores
      responsivity in mother-infant communication by modeling how change in guiding
      language between 7 and 11 months influences toddler vocabulary development. In a
      group of 32 mother-child dyads, change in early maternal guiding language
      positively predicted child language outcomes measured at 18 and 24 months. In
      contrast, a number of other linguistic variables - including total utterances and
      non-guiding language - did not correlate with toddler vocabulary development,
      suggesting a critical role of responsive change in infant-directed communication.
      We further assessed whether maternal affect during early communication influenced
      toddler vocabulary outcomes, finding that dominant affect during early mother
      infant communications correlated to lower child language outcomes. These findings
      provide evidence that responsive parenting should not only be assessed
      longitudinally, but unique contributions of language and affect should also be
      concurrently considered in future study.

PMID- 29457575
TI  - Testing the effect of an arbitrary subject pronoun on relative clause
      comprehension: a study with Hebrew-speaking children.
AB  - Previous studies have found that Hebrew-speaking children accurately comprehend
      object relatives (OR) with an embedded non-referential arbitrary subject pronoun
      (ASP). The facilitation of ORs with embedded pronouns is expected both from a
      discourse-pragmatics perspective and within a syntax-based locality approach.
      However, the specific effect of ASP might also be driven by a mismatch in
      grammatical features between the head noun and the pronoun, or by its relatively
      undemanding referential properties. We tested these possibilities by comparing
      ORs whose embedded subject is either ASP, a referential pronoun, or a lexical
      noun phrase. In all conditions, grammatical features were controlled. In a
      referent-identification task, the matching features made ORs with embedded
      pronouns difficult for five-year-olds. Accuracy was particularly low when the
      embedded pronoun was referential. These results indicate that embedded pronouns
      do not facilitate ORs across the board, and that the referential properties of
      pronouns affect OR processing.

PMID- 29457576
TI  - Hypoalbuminaemia as a marker of trans-capillary leakage in community-acquired
      bacteraemia patients.
AB  - Community-acquired bacteraemia patients (n = 2472), Denmark, 2000-2008. Albumin,
      C-reactive protein (CRP) and haemoglobin (Hb) measured 2000-2010. We assessed
      daily mean levels of albumin, CRP and Hb from 30 days before to 30 days after
      bacteraemia and correlations between albumin vs. CRP and albumin vs. Hb. In
      linear regression models, we evaluated the contribution of CRP, Hb, chronic and
      acute variables to the albumin level variations. The mean albumin level (33.6
      g/l) was steady before day 1, declined to 29.3 g/l on day 1 with little increase
      afterward. The mean CRP increased from day -5, peaked on day 1 and declined
      thereafter. The mean Hb level was fairly constant during days -30/30. Albumin was
      inversely (R range, - 0.18/-0.47, P < 10-4) correlated with the CRP level and
      positively (R = 0.17-0.46, P < 10-4) correlated with the HB level. In most
      models, CRP was the first variable that contributed to the albumin variations, 34
      70% of the full model. The sudden decrease of albumin levels, without sudden
      fluctuations of CRP or Hb, indicated that hypoalbuminaemia was a marker of trans
      capillary leakage.

PMID- 29457577
TI  - Space, place and (waiting) time: reflections on health policy and politics.
AB  - Health systems have repeatedly addressed concerns about efficiency and equity by
      employing trans-national comparisons to draw out the strengths and weaknesses of
      specific policy initiatives. This paper demonstrates the potential for explicit
      historical analysis of waiting times for hospital treatment to add value to
      spatial comparative methodologies. Waiting times and the size of the lists of
      waiting patients have become key operational indicators. In the United Kingdom,
      as National Health Service (NHS) financial pressures intensified from the 1970s,
      waiting times have become a topic for regular public and political debate.
      Various explanations for waiting times include the following: hospital
      consultants manipulate NHS waiting lists to maintain their private practice;
      there is under-investment in the NHS; and available (and adequate) resources are
      being used inefficiently. Other countries have also experienced ongoing tensions
      between the public and private delivery of universal health care in which
      national and trans-national comparisons of waiting times have been regularly
      used. The paper discusses the development of key UK policies, and provides a
      limited Canadian comparative perspective, to explore wider issues, including
      whether 'waiting crises' were consciously used by policymakers, especially those
      brought into government to implement new economic and managerial strategies, to
      diminish the autonomy and authority of the medical professional in the hospital
      environment.

PMID- 29457578
TI  - An Undiagnosed Index Case Leading to a Nosocomial Scabies Outbreak: How Mass
      Single-Dose Ivermectin Treatment Can Help Control a Nosocomial Epidemic.

PMID- 29457579
TI  - Clinical Relevance of the 2014 and 2015 National Healthcare Safety Network's
      Catheter-Associated Urinary Tract Infection Definitions.

PMID- 29457580
TI  - Food and beverage intakes according to physical activity levels in European
      children: the IDEFICS (Identification and prevention of Dietary and lifestyle
      induced health EFfects In Children and infantS) study.
AB  - OBJECTIVE: Physical activity (PA) levels and dietary habits are considered some
      of the most important factors associated with obesity. The present study aimed to
      examine the association between PA level and food and beverage consumption in
      European children (2-10 years old).Design/Setting/SubjectsA sample of 7229
      children (49.0 % girls) from eight European countries participating in the
      IDEFICS (Identification and prevention of Dietary and lifestyle induced health
      EFfects In Children and infantS) study was included. Moderate-to-vigorous PA
      (MVPA) was assessed objectively with accelerometers. FFQ was used to register
      dietary habits. ANCOVA and binary logistic regression were applied. RESULTS: Boys
      who spent less time in MVPA reported lower consumption of vegetables, fruits,
      cereals, yoghurt, milk, bread, pasta, candies and sugar-sweetened beverages (SSB)
      than boys who spent more time in MVPA (P<0.05). Moreover, boys who spent less
      time in MVPA were more likely to consume fast foods and water than those in the
      highest MVPA tertile (P<0.05). Girls who spent less time in MVPA reported lower
      consumption frequencies of vegetables, pasta, bread, yoghurt, candies, jam/honey
      and SSB than girls in the highest MVPA tertile (P<0.05). Also, girls in the
      lowest MVPA tertile were more likely to consume fast foods and water than those
      with high levels of MVPA (P<0.05). CONCLUSIONS: Food intake among European
      children varied with different levels of daily MVPA. Low time spent in MVPA was
      associated with lowest consumption of both high- and low-energy-dense foods and
      high fast-food consumption.

PMID- 29457581
TI  - Association between TLR2 + 2477G/A polymorphism and bacterial meningitis: a meta
      analysis.
AB  - Toll-like receptor 2 (TLR2) is a key member of TLRs, which is crucial in the
      initial inflammatory response against bacteria. TLR2, is also the initial barrier
      against bacterial infection and plays an important role in recognising a variety
      of bacterial lipoproteins. Several studies have been performed to investigate the
      TLR2 + 2477G/A polymorphism and bacterial meningitis susceptibility.
      Unfortunately, the results of previous studies were controversial. Therefore, we
      performed a meta-analysis to derive a more precise estimation of the association.
      The association between the TLR2 + 2477G/A polymorphism and bacterial meningitis
      susceptibility was assessed by odds ratios together with their 95% confidence
      intervals (CI). Six studies were enrolled in the present meta-analysis. Overall,
      no significant association between TLR2 + 2477G/A polymorphism and bacterial
      meningitis risk were found under allele contrast (A vs. G: OR = 1.15, 95% CI =
      0.93-1.43, P = 0.202), recessive genetic model (AA vs. AG/GG: OR = 1.12, 95% CI =
      0.90-1.41, P = 0.313). The significant association was found between TLR2 +
      2477G/A polymorphism and pneumococcal meningitis risk under allele contrast (A
      vs. G: OR = 1.54, 95% CI = 1.01-2.36, P = 0.046), recessive genetic model (AA vs.
      AG/GG: OR = 1.63, 95% CI = 1.03-2.57, P = 0.035). We conclude that TLR2 + 2477G/A
      polymorphism is not associated with meningococcal meningitis risk but contributes
      an increased risk of pneumococcal meningitis.

PMID- 29457582
TI  - Green leafy and cruciferous vegetable consumption and risk of type 2 diabetes:
      results from the Singapore Chinese Health Study and meta-analysis.
AB  - Several previous prospective studies suggest that consumption of green leafy and
      cruciferous vegetables may lower the risk of type 2 diabetes (T2D). We
      investigated the association between consumption of different types of vegetables
      in relation to T2D risk in an Asian Population. We included 45 411 participants
      (age range: 45-74 years) of the Singapore Chinese Health Study (SCHS) free of
      diabetes, cancer or CVD at baseline (1993-1998). Dietary information was
      collected using a validated FFQ. Physician-diagnosed incident diabetes was
      reported at follow-up I (1999-2004) and II (2006-2010) interviews. Cox
      proportional hazards regression was used to estimate hazard ratio (HR) and 95 %
      CI of T2D risk. An updated meta-analysis was also conducted to summarise results
      for green leafy and cruciferous vegetables. During 494 741 person-years of follow
      up, 5207 incident T2D occurred. After adjustment for potential confounders,
      neither total vegetables (top v. bottom quintile HR=1.08; 95 % CI 0.98, 1.18, P
      trend=0.66) nor specific vegetables including dark green leafy vegetables
      (HR=1.05; 95 % CI 0.96, 1.15, P trend=0.21) and cruciferous vegetables (HR=0.97;
      95 % CI 0.88, 1.06, P trend=0.29) were substantially associated with risk of T2D.
      A meta-analysis (eleven studies with 754 729 participants and 58 297 cases)
      including the SCHS and all previous prospective studies suggested borderline
      significant inverse associations between green leafy (summary relative risk
      (RR)=0.91; 95 % CI 0.84, 1.00) and cruciferous vegetable consumption (RR=0.87; 95
      % CI 0.76, 1.00) and T2D risk, with moderate-to-high heterogeneity. In
      conclusion, green leafy or cruciferous vegetable consumption was not
      substantially associated with risk of T2D in an Asian population. Meta-analysis
      of available cohort data indicated that evidence for a beneficial effect of green
      leafy or cruciferous vegetable consumption on T2D risk is not convincing.

PMID- 29457583
TI  - Financial Incentives to Reduce Hospital-Acquired Infections Under Alternative
      Payment Arrangements.
AB  - OBJECTIVEThe financial incentives for hospitals to improve care may be weaker if
      higher insurer payments for adverse conditions offset a portion of hospital
      costs. The purpose of this study was to simulate incentives for reducing hospital
      acquired infections under various payment configurations by Medicare, Medicaid,
      and private payers.DESIGNMatched case-control study.SETTINGA large, urban
      hospital system with 1 community hospital and 2 tertiary-care
      hospitals.PATIENTSAll patients discharged in 2013 and 2014.METHODSUsing
      electronic hospital records, we identified hospital-acquired bloodstream
      infections (BSIs) and urinary tract infections (UTIs) with a validated algorithm.
      We assessed excess hospital costs, length of stay, and payments due to infection,
      and we compared them to those of uninfected patients matched by propensity for
      infection.RESULTSIn most scenarios, hospitals recovered only a portion of excess
      HAI costs through increased payments. Patients with UTIs incurred incremental
      costs of $6,238 (P<.01), while payments increased $1,901 (P<.05) at public
      diagnosis-related group (DRG) rates. For BSIs, incremental costs were $15,367
      (P<.01), while payments increased $7,895 (P<.01). If private payers reimbursed a
      200% markup over Medicare DRG rates, hospitals recovered 55% of costs from BSI
      and UTI among private-pay patients and 54% for BSI and 33% for UTI, respectively,
      across all patients. Under per-diem payment for private patients with no markup,
      hospitals recovered 71% of excess costs of BSI and 88% for UTI. At 150% markup
      and per-diem payments, hospitals profited.CONCLUSIONSHospital incentives for
      investing in patient safety vary by payer and payment configuration. Higher
      payments provide resources to improve patient safety, but current payment
      structures may also reduce the willingness of hospitals to invest in patient
      safety.Infect Control Hosp Epidemiol 2018;39:509-515.

PMID- 29457584
TI  - Immunological Stability of Clostridium difficile Toxins in Clinical Specimens.
AB  - OBJECTIVE The impact of storage on stability and detection of Clostridium
      difficile toxins in feces is poorly understood. The objective of this study was
      to investigate the immunological stability of C. difficile toxins in clinical
      stool specimens under different storage conditions by evaluating this stability
      using toxin detection by enzyme immunoassay (EIA). METHODS Stool specimens
      positive for C. difficile infection (CDI) by quantitative polymerase chain
      reaction (qPCR) were used for EIA testing with the C. difficile Tox A/B II kit.
      The EIA-positive specimens were stored aerobically under refrigerated (4-10
      degrees C) and frozen (-30 degrees C and -80 degrees C) conditions. Measurement
      of toxin quantity was conducting using optical density (OD) on days 0, 14, 30,
      60, 90, and 120 of storage. RESULTS Clostridium difficile toxins demonstrated
      good detection in undiluted stool specimens by EIA up to 120 days of storage.
      Good detection of the toxins was observed in diluted samples at refrigerated and 
      80 degrees C temperatures. Dilution detrimentally affected toxin detection at -30
      degrees C. CONCLUSION Storage of undiluted clinical stool specimens at
      refrigerated, -30 degrees C, and -80 degrees C temperatures for up to 120 days
      has no discernible effect on the immunological stability of C. difficile
      cytotoxins. However, storage at -30 degrees C has a detrimental effect on C.
      difficile toxin stability in diluted specimens. Infect Control Hosp Epidemiol
      2018;39:434-438.

PMID- 29457585
TI  - Training nurses in a competency framework to support adults with epilepsy and
      intellectual disability: the EpAID cluster RCT.
AB  - BACKGROUND: People with an intellectual (learning) disability (ID) and epilepsy
      have an increased seizure frequency, higher frequencies of multiple antiepileptic
      drug (AED) use and side effects, higher treatment costs, higher mortality rates
      and more behavioural problems than the rest of the population with epilepsy. The
      introduction of nurse-led care may lead to improvements in outcome for those with
      an ID and epilepsy; however, this has not been tested in a definitive clinical
      trial. OBJECTIVE: To determine whether or not ID nurses, using a competency
      framework developed to optimise nurse management of epilepsy in people with an
      ID, can cost-effectively improve clinical and quality-of-life outcomes in the
      management of epilepsy compared with treatment as usual. DESIGN: Cluster
      randomised two-arm trial. SETTING: Community-based secondary care delivered by
      members of community ID teams. PARTICIPANTS: Participants were adults aged 18-65
      years with an ID and epilepsy under the care of a community ID team and had had
      at least one seizure in the 6 months before the trial. INTERVENTIONS: The
      experimental intervention was the Learning Disability Epilepsy Specialist Nurse
      Competency Framework. This provides guidelines describing a structure and goals
      to support the delivery of epilepsy care and management by ID-trained nurses.
      MAIN OUTCOME MEASURES: The primary outcome was the seizure severity scale from
      the Epilepsy and Learning Disabilities Quality of Life questionnaire. Measures of
      mood, behaviour, AED side effects and carer strain were also collected. A cost
      utility analysis was undertaken along with a qualitative examination of carers'
      views of participants' epilepsy management. RESULTS: In total, 312 individuals
      were recruited into the study from 17 research clusters. Using an intention-to
      treat analysis controlling for baseline individual-level and cluster-level
      variables there was no significant difference in seizure severity score between
      the two arms. Altogether, 238 complete cases were included in the non-imputed
      primary analysis. Analyses of the secondary outcomes revealed no significant
      differences between arms. A planned subgroup analysis identified a significant
      interaction between treatment arm and level of ID. There was a suggestion in
      those with mild to moderate ID that the competency framework may be associated
      with a small reduction in concerns over seizure severity (standard error 2.005,
      95% confidence interval -0.554 to 7.307; p = 0.092). However, neither subgroup
      showed a significant intervention effect individually. Family members'
      perceptions of nurses' management depended on the professional status of the
      nurses, regardless of trial arm. Economic analysis suggested that the competency
      framework intervention was likely to be cost-effective, primarily because of a
      reduction in the costs of supporting participants compared with treatment as
      usual. LIMITATIONS: The intervention could not be delivered blinded. Treatment as
      usual varied widely between the research sites. CONCLUSIONS: Overall, for adults
      with an ID and epilepsy, the framework conferred no clinical benefit compared
      with usual treatment. The economic analysis suggested that there may be a role
      for the framework in enhancing the cost-effectiveness of support for people with
      epilepsy and an ID. Future research could explore the specific value of the
      competency framework for those with a mild to moderate ID and the potential for
      greater long-term benefits arising from the continuing professional development
      element of the framework. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN96895428. FUNDING: This trial was funded by the NIHR Health Technology
      Assessment programme and will be published in full in Health Technology
      Assessment; Vol. 22, No. 10. See the NIHR Journals Library website for further
      project information.

PMID- 29457586
TI  - Origin of distorted 1T-phase ReS2: first-principles study.
AB  - Group-VIIB transition metal dichalcogenides (TMDCs) are known to be stabilized
      solely in a distorted 1T phase termed as 1T" phase, which is compared to many
      stable or metastable phases in other TMDCs. Using first-principles calculations,
      we study the structural origin of 1T" phase group-VIIB TMDCs. We find that quasi
      1D Peierls-like instability is responsible for the transition to the 1T" phase
      ReS2 monolayer from the 1T' phase, another distorted 1T phase. Two half-filled
      bands in 1T'-ReS2 make sharp peaks in the Lindhard function that prompt the
      charge density wave (CDW) phase with large band gap opening. Our calculations
      show that overlapping of the two bands in a broad energy range leads to robust
      CDW phase or stable 1T" phase in group-VIIB TMDCs against compositional
      variation, which is in stark contrast to typical Peierls instability driven by a
      single band. Calculated total energy curve near the critical point exhibits the
      feature of the first-order Landau transition due to local chemical bonding. The
      structural stability of the 1T" phase in group-VIIB TMDCs is thus guaranteed by
      two half-filled bands and local chemical bonding.

PMID- 29457587
TI  - Power cavitation-guided blood-brain barrier opening with focused ultrasound and
      microbubbles.
AB  - Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies
      relies on the accurate localization of FUS-stimulated microbubble activity (i.e.
      acoustic cavitation). Passive cavitation imaging with ultrasound arrays can
      achieve this, but with insufficient spatial resolution. In this study, we address
      this limitation and perform high-resolution monitoring of acoustic cavitation
      mediated blood-brain barrier (BBB) opening with a new technique called power
      cavitation imaging. By synchronizing the FUS transmit and passive receive
      acquisition, high-resolution passive cavitation imaging was achieved by using
      delay and sum beamforming with absolute time delays. Since the axial image
      resolution is now dependent on the duration of the received acoustic cavitation
      emission, short pulses of FUS were used to limit its duration. Image sets were
      acquired at high-frame rates for calculation of power cavitation images analogous
      to power Doppler imaging. Power cavitation imaging displays the mean intensity of
      acoustic cavitation over time and was correlated with areas of acoustic
      cavitation-induced BBB opening. Power cavitation-guided BBB opening with FUS
      could constitute a standalone system that may not require MRI guidance during the
      procedure. The same technique can be used for other acoustic cavitation-based FUS
      therapies, for both safety and guidance.

PMID- 29457588
TI  - TiO2 nanotubes with different spacing, Fe2O3 decoration and their evaluation for
      Li-ion battery application.
AB  - In the present work, we report on the use of organized TiO2 nanotube (NT) layers
      with a regular intertube spacing for the growth of highly defined alpha-Fe2O3
      nano-needles in the interspace. These alpha-Fe2O3 decorated TiO2 NTs are then
      explored for Li-ion battery applications and compared to classic close-packed
      (CP) NTs that are decorated with various amounts of nanoscale alpha-Fe2O3. We
      show that NTs with tube-to-tube spacing allow uniform decoration of individual
      NTs with regular arrangements of hematite nano-needles. The tube spacing also
      facilitates the electrolyte penetration as well as yielding better ion diffusion.
      While bare CP NTs show a higher capacitance of 71 MUAh cm-2 compared to bare
      spaced NTs with a capacitance of 54 MUAh cm-2, the hierarchical decoration with
      secondary metal oxide, alpha-Fe2O3, remarkably enhances the Li-ion battery
      performance. Namely, spaced NTs with alpha-Fe2O3 decoration have an areal
      capacitance of 477 MUAh cm-2, i.e. they have nearly ~8 times higher capacitance.
      However, the areal capacitance of CP NTs with alpha-Fe2O3 decoration saturates at
      208 MUAh cm-2, i.e. is limited to ~3 times increase.

PMID- 29457589
TI  - Short-term efficacy of pipeline embolization device for treating complex
      intracranial aneurysms.
AB  - OBJECTIVE: To observe the short-term efficacy of Pipeline embolization divice
      (PED) for the treatment of complex intracranial aneurysms. METHODS: The clinical
      data of 29 consecutive patients with 32 intracranial aneurysms treated with PED
      between April 2015 to September 2016 were analyzed retrospectively. There were 3
      small aneurysm, 15 large aneurysms, 8 giant aneurysms, 5 fusiform ayneurysms and
      1 recidivation. The vessels include 25 anterior circulation and 4 posterior
      circulation. RESULTS: We treated 31 aneurysms with 30 PEDs and all of the stents
      were implanted successfully. 1 case of single aneurysm was multiple divices
      implanted and 1 case of 3 aneurysms were treated by single PED. 12 of the 29
      patients were implanted PED only, 17 were implanted PED with coils, 2 underwent
      balloon remodeling after the PED implanted. The ostia of 19 ophthalmic arteries,
      10 posterior communicating arteries, 4 posterior inferior cerebellar arteries and
      1 anterior cerebral artery were covered by PED during procedures; 1 ophthalmic
      arteries and 1 posterior communicating artery disappeared, no branch vessels
      occlusion and parent artery stenosis occurred.Hemorrhagic complacations occurred
      in 2 patients, 2 hours and 5 days after procedure respectively. Radiographic
      follow-up examnations were carried out in 24 patients and revealed complete
      occlusion in 21 patients, uncomplete occlusion in 3 patients. No neurological
      injure occurred in 27 patients who received a clinical follow-up. CONCLUSION: PED
      provide a safe and effective methord for the treatment of intracranial complex
      aneurysms like wide-neck aneurysms, fusiform aneurysms, giant aneurysms in low
      risk of procedural complications and high rates of aneurysm occlusion.

PMID- 29457590
TI  - Investigation of mechanical compatibility of hernia meshes and human abdominal
      fascia.
AB  - OBJECTIVE: Understanding the biomechanical properties of hernia meshes is
      essential in facilitating their selection. The aim of this study was to evaluate
      the mechanical compatibility of hernia meshes and human abdominal fascia and
      assess their applicability in hernia repair. METHODS: Uniaxial tensile tests were
      performed. A total of eight hernia meshes were tested - three standard meshes
      (Surgimesh(r), SurgiproTM, TecnoMesh(r)) and five light-weight meshes
      (Optilene(r), TiO2MeshTM, ParietexTM, VyproTM II, UltraproTM). RESULTS: The
      secant modulus at 5% strain and the level of orthotropy (the ratio between
      tensile stress in the longitudinal and the transversal direction) at 5% strain
      were calculated from the stress-stretch ratio curves. The impact of pore size and
      thickness on the elastic properties of these meshes was determined. The
      relationships between density and elasticity as well as between elasticity and
      the strain developed at 16 N/cm load were presented. The resulting mechanical
      properties of meshes were compared to the elasticity, orthotropy and
      deformability of human abdominal fascia. CONCLUSIONS: VyproTM II and ParietexTM
      brands display properties similar to those of fascia in both directions. The
      TiO2MeshTM and UltraproTM display deformability close to the deformability at 16
      N/cm of the fascia transversalis. Only the VyproTM II brand's orthotropy is
      similar to that of fascia.

PMID- 29457591
TI  - Effects of polycaprolactone-biphasic calcium phosphate scaffolds on enhancing
      growth and differentiation of osteoblasts.
AB  - BACKGROUND: Polycaprolactone (PCL)-biphasic calcium phosphate (BCP) scaffolds
      fabricated using Melt-Stretching and Compression Molding (MSCM) can release
      calcium and phosphate ions, which are essential for bone formation. OBJECTIVE:
      Responses of the osteoblasts seeded on three groups of scaffolds including group
      A; PCL-20% BCP (%wt), group B; PCL-30% BCP and group C (control); pure PCL (100%
      PCL) were evaluated. METHODS: The cell-scaffold constructs were made by seeding
      osteoblast cell lines at 1*105 cells/scaffold. The constructs of each group were
      divided for culturing in proliferation medium (PR) and osteogenic induction
      medium (OS) for 30 days. RESULTS: The cells attached and grew on the scaffolds of
      all groups. The cell number and the differentiation markers of groups A and B
      were remarkably higher than those of group C over the observation periods. Slow
      proliferation of the cells of group A and B in the PR medium in the first 7 days
      corresponded to the maximum increases in alkaline phosphatase activities (ALP).
      The maximum levels of ALP of those groups in the OS medium were not detected
      until day 14. The levels of osteocalcin of those groups were not statistically
      different when cultured in both mediums. CONCLUSIONS: The MSCM scaffolds are
      suitable for supporting attachment and growth of the osteoblasts. Additional BCP
      into the PCL-based scaffolds accelerate early differentiation of the cells in the
      constructs even without osteogenic-inductive condition.

PMID- 29457592
TI  - PEGylated graphene oxide/Fe3O4 nanocomposite: Synthesis, characterization, and
      evaluation of its performance as de novo drug delivery nanosystem.
AB  - This paper describes the development of mitoxantrone-loaded PEGylated graphene
      oxide/magnetite nanoparticles (PEG-GO/Fe3O4-MTX), and investigation of its
      preliminary drug delivery performance. For this, the GO was synthesized through
      oxidizing graphite powder, and subsequently carboxylated using a substitution
      nucleophilic reaction. The carboxylated GO (GO-COOH) was then conjugated with
      amine end-caped PEG chains by Steglich esterification. Afterward, GO-PEG/Fe3O4
      nanocomposite was synthesized through the anchoring of Fe3O4 nanoparticles onto
      the surface of GO-PEG during the sonication. The biocompatibility and MTX-loading
      capacity of the synthesized GO-PEG/Fe3O4 nanocomposite were evaluated. The pH
      dependent drug release behavior and cytotoxicity effect of the MTX-loaded GO
      PEG/Fe3O4 nanocomposite were also studied. According to biocompatibility, pH
      dependent drug release behavior as well as superior physicochemical and
      biological characteristics of graphene and magnetite nanoparticles, it is
      expected that the GO-PEG/Fe3O4 nanocomposite may be applied as de novo drug
      delivery system (DDS) for cancer therapy using both chemo- and photothermal
      therapy approaches.

PMID- 29457593
TI  - Characterization study and optimization of swelling behavior for p(HEMA-co
      Eudragit L-100) hydrogels by using Taguchi Method.
AB  - The aim of this study is to produce the smart hydrogel to use insulin release for
      human body. p(HEMA-co-Eudragit L-100) hydrogels containing different ratios of 2
      Hydroxyethyl methacrylate (HEMA) and Eudragait L-100 were synthesized by using
      ammonium persulfate (APS) as an initiator and ethylene glycol dimethacrylate
      (EGDMA) as a cross linker. The structures of hydrogels produced were
      characterized by using Fourier Transform Infrared Spectroscopy (FT-IR) and
      Scanning electron microscope (SEM) analysis. In this way, optimum synthesis
      conditions were determined for p(HEMA-co-Eudragit L-100) hydrogels by using
      Taguchi method as an optimization method. The gelling percentages of all
      hydrogels were calculated. After all, the swelling behaviors (%) of hydrogels
      were investigated in range of various times (1-44 hrs), temperatures (20-50
      degrees C) and pH (2-12) and the optimum process conditions in the production of
      hydrogels were determined. Consequently, the optimum time, temperature and pH
      were 24 hours, 37 degrees C and 7, respectively. Thus, this hydrogel could be
      evaluated in insulin release for diabetes treatment and drug industry.

PMID- 29457594
TI  - Biodistribution of colloidal gold nanoparticles after intravenous injection:
      Effects of PEGylation at the same particle size.
AB  - BACKGROUND: Recently, polyethylene glycol (PEG) modified gold nanoparticles have
      been studied to maintaining long-term stability in biological fluids. Its
      biodistribution was also reported, however, comparison of bare gold nanoparticles
      and PEGylated gold nanoparticles with equal particle size is not sufficient.
      OBJECTIVE: We prepared bare gold nanoparticles and PEGylated gold nanoparticles
      with diameters of 20-30-nm or 50-nm to avoid the influence of particle diameter,
      and studied their biodistribution in the mouse. METHODS: Gold concentrations in
      brain, heart, lungs, liver, stomach, pancreas, spleen, kidneys, blood, urine, and
      feces were measured at 0.5, 1, 2, 3, 6, 12, 18, 24, and 48 h after administration
      of gold nanoparticles using inductively coupled plasma atomic emission
      spectrometry. RESULTS: At 48 h after intravenous administration, accumulation in
      the liver and spleen was significantly reduced by PEGylation, and the gold
      amounts of PEGylated gold nanoparticles with diameters of 20-30 nm and 50-nm in
      the brain were 3.6 times and 2.7 times higher than those of bare gold
      nanoparticles, respectively. CONCLUSIONS: These results indicated that the
      usefulness of PEGylated gold nanoparticles with small particle size for a drug
      carrier.

PMID- 29457595
TI  - Minoxidil-encapsulated poly(L-lactide-co-glycolide) nanoparticles with hair
      follicle delivery properties prepared using W/O/W solvent evaporation and
      sonication.
AB  - BACKGROUND: Nanoparticles with a diameter of 100-150 nm prepared using
      poly(lactide-co-glycolide) can be delivered to hair follicles. Moreover, it was
      shown that drug release from nanoparticles was prolonged by using poly(L-lactide
      co-glycolide) (PLLGA). OBJECTIVE: The aim of this study was to prepared minoxidil
      encapsulated PLLGA nanoparticles and accumulate minoxidil in hair follicles
      utilizing its drug delivery properties for effective treatment of male and female
      androgenetic alopecia. METHODS: Minoxidil-encapsulated PLLGA nanoparticles were
      prepared using W/O/W solvent evaporation and sonication, and the ability of PLLGA
      nanoparticles to deliver to hair follicles was evaluated by in vivo transdermal
      delivery study using C3H/He mice and tape stripping and cyanoacrylate skin
      surface biopsy. RESULTS: Eight hours after administration of samples, minoxidil
      encapsulated PLLGA nanoparticles delivered 3.1 times more minoxidil in stratum
      corneum and 2.5 times more in hair follicles r compared to minoxidil aqueous
      solution. In addition, we found that 4.8% of the dose of minoxidil-encapsulated
      PLLGA nanoparticles were delivered to the hair follicles. CONCLUSIONS: In this
      study, it was shown that nanoparticulation using PLLGA7510 suppressed minoxidil
      release from nanoparticles and improved drug delivery amount to hair follicles.

PMID- 29457596
TI  - Evaluation of osteoinductive calcium phosphate ceramics repairing alveolar cleft
      defects in dog model.
AB  - BACKGROUND: Alveolar cleft repair is an important step in the sequence of
      treatments for cleft lip and palate. Intrinsically osteoinductive materials have
      been the subject of research interest. OBJECTIVE: The aim of this study was to
      explore the use of osteoinductive biphasic calcium phosphate (BCP) ceramics to
      repair alveolar cleft defects in dogs. METHODS: We prepared two kinds of BCP
      ceramic with different physical characteristics: osteoinductive BCP (OBCP) and
      non-osteoinductive BCP (NBCP). Bilateral alveolar cleft models were surgically
      established in dogs. On one side, OBCP was implanted in the defect; on the
      opposite side NBCP was implanted as a control. The materials were also implanted
      in the femoral muscles to test their properties at non-osseous sites. The
      osteogenic ability of materials was evaluated with imaging, spiral CT, histology
      and fluorescent dye tests. RESULTS: At the muscular implantation sites, new bone
      formed in all of the OBCP samples, but none in the NBCP samples. Imaging and
      spiral CT revealed good appearance and continuity of the alveolar cleft
      postoeration, with normal eruption of the bilateral permanent teeth in the
      groups. Histological and fluorescent dye testing revealed new bone formation in
      both groups in situ. However, earlier osteogenesis initiation and bone remodeling
      were superior with OBCP. Osteogenic process in the intramuscular samples with
      OBCP was similar to that seen in situ. CONCLUSIONS: Our findings indicated that
      osteoinductive biphasic calcium phosphate ceramics (OBCP) have superior
      characteristics in alveolar cleft repair compared with non-osteoinductive calcium
      phosphate ceramics (NBCP).

PMID- 29457597
TI  - Injectable collagen/RGD systems for bone tissue engineering applications.
AB  - Imbalance crosslink density and polymer concentration gradient is formed within
      the traditional alginate hydrogel using calcium chloride as a crosslinking agent
      in external gelation for instantaneously process. In this studying, type I
      collagen (Col I) blended calcium salt form of poly(gamma-glutamic acid)
      (gammaCaPGA) was mixing with RGD-modified alginate with convenient gelation
      process and suitable for practical use. The hydrophilicity of the resulting
      hydrogels was evaluated through swelling tests, water retention capacity tests,
      and water vapor permeation tests. Mineralization was qualitatively evaluated by
      alizarin red dyeing at day 14, verifying the deposition of calcium. The in vitro
      osteogenic differentiation is monitored by determining the early and late
      osteocalcin (OCN) and osteopontin (OPN) markers with MG63 cells. Obtained results
      demonstrated that no extremely changes in mechanical properties. After 14 days of
      culture, hydrogels significantly stimulated OCN/OPN gene expressions and MG63
      cell proliferation. Unusually, gammaCaPGA with RGD-modified alginate appeared
      better calcium deposition in 14 days than the other. However, addition of Col I
      can counterpoise RGD effect in blood coagulation and platelet adhesion made the
      hydrogel more flexibility and selectively in use. This studying provided that non
      covalently crosslinked hydrogel by gammaCaPGA with alginate can be upgrading by
      RGD and Col I in water uptake capability, obviously effective for MG63 cells and
      are remarkably biocompatible and exhibited no cytotoxicity. Moreover, results
      also displayed the injectable process without complicated procedure, have high
      cost/performance ratio and have great potential for bone regeneration.

PMID- 29457598
TI  - In vivo biocompatibility and degradation of novel Polycaprolactone-Biphasic
      Calcium phosphate scaffolds used as a bone substitute.
AB  - BACKGROUND: Biocompatibility and degradation of poly epsilon-caprolactone (PCL)
      Biphasic Calcium Phosphate (BCP) scaffolds fabricated by the "Melt Stretching and
      Compression Molding (MSCM)" technique were evaluated in rat models. OBJECTIVES:
      Degradation behaviors and histological biocompatibility of the PCL-20% BCP MSCM
      scaffolds and compare with those of PCL-20% beta-tricalcium phosphate (TCP)
      scaffolds commercially fabricated by Fused Deposition Modeling (FDM) were
      evaluated. METHODS: The study groups included Group A: PCL-20% BCP MSCM scaffolds
      and Group B: PCL-20% TCP FDM scaffolds, which were implanted subcutaneously in
      twelve male Wistar rats. On day 14, 30, 60 and 90, dimensional changes of the
      scaffolds and their surrounding histological features were assessed using Micro
      Computed Tomography (MU-CT) and histological analysis. Changes of their molecular
      weight were assessed using Gel Permeation Chromatography (GPC). RESULTS:
      Formation of collagen and new blood vessels throughout the scaffolds of both
      groups increased with time with low degrees of inflammation. The MU-CT and GPC
      analysis demonstrated that the scaffolds of both groups degraded with time, but,
      their molecular weight slightly changed over the observation periods. All results
      of both groups were not significantly different. CONCLUSIONS: The PCL-20% BCP
      MSCM scaffolds were biocompatible and biodegradable in vivo. Their properties
      were comparable to those of the commercial PCL-20% TCP scaffolds.

PMID- 29457599
TI  - Conclusions about testosterone therapy and cardiovascular risk.

PMID- 29457600
TI  - Public online information about tinnitus: A cross-sectional study of YouTube
      videos.
AB  - Purpose: To examine the information about tinnitus contained in different video
      sources on YouTube. Materials and Methods: The 100 most widely viewed tinnitus
      videos were manually coded. Firstly, we identified the sources of upload:
      consumer, professional, television-based clip, and internet-based clip. Secondly,
      the videos were analyzed to ascertain what pertinent information they contained
      from a current National Institute on Deafness and Other Communication Disorders
      fact sheet. Results: Of the videos, 42 were consumer-generated, 33 from media,
      and 25 from professionals. Collectively, the 100 videos were viewed almost 9
      million times. The odds of mentioning "objective tinnitus" in professional videos
      were 9.58 times those from media sources [odds ratio (OR) = 9.58; 95% confidence
      interval (CI): 1.94, 47.42; P = 0.01], whereas these odds in consumer videos were
      51% of media-generated videos (OR = 0.51; 95% CI: 0.20, 1.29; P = 0.16). The odds
      that the purpose of a video was to sell a product or service were nearly the same
      for both consumer and professional videos. Consumer videos were found to be 4.33
      times as likely to carry a theme about an individual's own experience with
      tinnitus (OR = 4.33; 95% CI: 1.62, 11.63; P = 0.004) as media videos.
      Conclusions: Of the top 100 viewed videos on tinnitus, most were uploaded by
      consumers, sharing individuals' experiences. Actions are needed to make
      scientific medical information more prominently available and accessible on
      YouTube and other social media.

PMID- 29457601
TI  - Influences of combined traffic noise on the ability of learning and memory in
      mice.
AB  - Objective: The present study aimed to evaluate the influences of combined traffic
      noise (CTN) on the ability of learning and memory in mice. Materials and Methods:
      The Institute of Cancer Research (ICR) mice were exposed to CTN from highways and
      high-speed railways for 42 days, whose day-night equivalent continuous A-weighted
      sound pressure level (Ldn) was 70 dB(A). On the basis of behavioral reactions in
      Morris water maze (MWM) and the concentrations of amino acid neurotransmitters in
      the hippocampus, the impacts of CTN on learning and memory in mice were examined.
      Results: The MWM test showed that the ability of learning and memory in mice was
      improved after short-term exposure (6-10 days, the first batch) to 70 dB(A) CTN,
      which showed the excitatory effect of stimuli. Long-term exposure (26-30 days,
      the third batch; 36-40 days, the fourth batch) led to the decline of learning and
      memory ability, which indicated the inhibitory effect of stimuli. Assays testing
      amino acid neurotransmitters showed that the glutamate level of the experimental
      group was higher than that of the control group in the first batch. However, the
      former was lower than the latter in the third and fourth batches. Both,
      behavioral reactions and the concentrations of amino acid neurotransmitters,
      testified that short-term exposure and long-term exposure resulted in excitatory
      effect and inhibitory effect on the ability of learning and memory, respectively.
      Conclusion: The effects of 70 dB(A) CTN on the ability of learning and memory
      were closely related to the exposure duration. Furthermore, those effects were
      regulated and controlled by the level of glutamate in the hippocampus.

PMID- 29457602
TI  - Examination of previously published data to identify patterns in the social
      representation of "Loud music" in young adults across countries.
AB  - Purpose: The current study was aimed at understanding the patterns in the social
      representation of loud music reported by young adults in different countries.
      Materials and Methods: The study included a sample of 534 young adults (18-25
      years) from India, Iran, Portugal, United Kingdom, and United States.
      Participants were recruited using a convince sampling, and data were collected
      using the free association task. Participants were asked to provide up to five
      words or phrases that come to mind when thinking about "loud music." The data
      were first analyzed using the qualitative content analysis. This was followed by
      quantitative cluster analysis and chi-square analysis. Results: The content
      analysis suggested 19 main categories of responses related to loud music. The
      cluster analysis resulted in for main clusters, namely: (1) emotional oriented
      perception; (2) problem oriented perception; (3) music and enjoyment oriented
      perception; and (4) positive emotional and recreation-oriented perception.
      Country of origin was associated with the likelihood of participants being in
      each of these clusters. Conclusion: The current study highlights the differences
      and similarities in young adults' perception of loud music. These results may
      have implications to hearing health education to facilitate healthy listening
      habits.

PMID- 29457603
TI  - The hearing of rural workers exposed to noise and pesticides.
AB  - n work environments, different physical and chemical agents that may pose a risk
      to workers' hearing health coexist. In this context, occupational hearing loss
      stands out. It has mostly been attributed to only noise exposure, although there
      are other agents, that is, pesticides that might contribute to occupational
      hearing loss. In this report, two cases will be presented that consider rural
      workers exposed to pesticides and intense noise generated by an adapted
      rudimentary vehicle. The noise measured in this vehicle was 88.3 dBA up to 93.4
      dBA. Pure-tone audiometry, distortion product otoacoustic emissions, and high
      frequency audiometry tests were performed. This report is unusual because of the
      short time of exposure to noise and pesticides and the hearing loss found,
      indicating a synergy between those agents.

PMID- 29457604
TI  - Cathodal neuromodulation of dominant temporoparietal cortex with transcranial
      direct current stimulation for tinnitus: A case series.
AB  - There is scant literature on the effectiveness of using transcranial direct
      current stimulation (tDCS) as an intervention modality for managing tinnitus. The
      current case series reflects the use of tDCS as an effective intervention for
      tinnitus while inhibiting the dominant temporoparietal cortex and simultaneous
      stimulating the non-dominant dorsolateral prefrontal cortex.

PMID- 29457607
TI  - Ultra-high aspect ratio hybrid materials: the role of organic guest and synthesis
      method.
AB  - Hybrid organic-inorganic layered double hydroxide materials have been prepared
      with an ultra-high aspect ratio via an environmentally friendly co-hydration
      approach where metal hydroxides and adamantane-carboxylic acid were used as the
      reagents. The method avoids use of either acidic or basic precipitation methods,
      or using a large excess of anion. The effect of organic anion, metal cation and
      synthesis method on developing ultra-high aspect ratio crystallites was studied.

PMID- 29457605
TI  - Negative Pressure Therapy in the Regeneration of the Sciatic Nerve Using Vacuum -
      Assisted Closure in a Rabbit Model.
AB  - BACKGROUND The aim of this study was to investigate the effects of negative
      pressure therapy in the regeneration of the rabbit sciatic nerve using vacuum
      assisted closure (VAC). MATERIAL AND METHODS Thirty male New Zealand white
      rabbits underwent surgical injury of the sciatic nerve, followed by negative
      pressure therapy using vacuum assisted closure (VAC), in three treatment groups:
      Group A: 0 kPa; Group B: -20 kPa; Group C: -40 kPa. At 12 weeks following
      surgery, the following factors were studied: motor nerve conduction velocity
      (MNCV); the number of myelinated nerve fibers; the wet weight of the
      gastrocnemius muscle. Gastrocnemius muscle and sciatic nerve tissue samples were
      studied for the expression of S100, and brain-derived neurotrophic factor (BDNF)
      using Western blot. RESULTS At 12 weeks following VAC treatment, the MNCV, number
      of myelinated nerve fibers, and wet weight of the gastrocnemius muscle showed
      significant differences between the groups (p<0.05), in the following order:
      Group B >Group A >Group C. The sciatic nerve at 12 weeks following VAC in Group B
      and Group C showed a significant increase in expression of S100 and BDNF when
      compared with Group A; no significant differences were detected between Group B
      and Group C results from Western blot at 12 weeks. CONCLUSIONS The findings of
      this study, using negative pressure therapy in VAC in a rabbit model of sciatic
      nerve damage, have shown that moderate negative pressure was beneficial, but high
      values did not benefit sciatic nerve repair.

PMID- 29457608
TI  - Redox-responsive UCNPs-DPA conjugated NGO-PEG-BPEI-DOX for imaging-guided PTT and
      chemotherapy for cancer treatment.
AB  - The disulfide bond (-S-S-) is an enormously valuable functional group in a
      variety of chemical and biological agents that display effective reactivity or
      biological activities (e.g., antitumor activities). The disulfide bonds prevalent
      in proteins are somewhat oxidizing in the extracellular space; however, such
      disulfide bonds can rarely be found inside cells because of disulfide cleavage
      reactions facilitated by abundant free cellular thiols, including glutathione
      (GSH), which is the most important common thiol-containing small molecule.
      Interestingly, intracellular GSH concentrations are considerably higher in cancer
      cells than in analogous normal cells; this feature may prove to be significant in
      the development of anticancer drug delivery systems (DDS). Moreover, upconversion
      nanoparticles (UCNPs) have been extensively investigated in multimodal imaging,
      photodynamic therapy (PDT) and photothermal therapy. UCNPs exploit near-infrared
      excitation instead of ultraviolet excitation and possess exclusive properties,
      which include greatly increased penetration depth in biological samples and
      reductions in background autofluorescence, photobleaching and photodamage to
      biological specimens. These fascinating optical features of UCNPs may broaden
      their prospects in the fields of imaging and therapy. Graphene has emerged as a
      flat monolayer of carbon atoms that are tightly embedded in a two-dimensional
      (2D) honeycomb lattice. Widespread research has been carried out on graphene in
      recent years owing to its exclusive shape and size, as well as innumerable
      fascinating physical and chemical properties. Owing to their high optical
      absorption in the near-infrared (NIR) region, graphene and GO have been
      extensively employed for photothermal therapy (PTT). In this study, we attempted
      to merge the properties of these compounds by conjugating UCNPs and NGO-PEG-BPEI
      DOX into a single platform for chemotherapy and photothermal therapy.

PMID- 29457609
TI  - Feedback control of photoresponsive fluid interfaces.
AB  - Photoresponsive surfactants provide a unique microfluidic driving mechanism.
      Since they switch between two molecular shapes under illumination and thereby
      affect surface tension of fluid interfaces, Marangoni flow along the interface
      occurs. To describe the dynamics of the surfactant mixture at a planar interface,
      we formulate diffusion-advection-reaction equations for both surfactant
      densities. They also include adsorption from and desorption into the neighboring
      fluids and photoisomerization by light. We then study how the interface responds
      when illuminated by spots of light. Switching on a single light spot, the density
      of the switched surfactant spreads in time and assumes an exponentially decaying
      profile in steady state. Simultaneously, the induced radial Marangoni flow
      reverses its flow direction from inward to outward. We use this feature to set up
      specific feedback rules, which couple the advection velocities sensed at the
      light spots to their intensities. As a result two neighboring spots switch on and
      off alternately. Extending the feedback rule to light spots arranged on the
      vertices of regular polygons, we observe periodic switching patterns for even
      sided polygons, where two sets of next-nearest neighbors alternate with each
      other. A triangle and pentagon also show regular oscillations, while heptagon and
      nonagon exhibit irregular oscillations due to frustration. While our findings are
      specific to the chosen set of parameters, they show how complex patterns at
      photoresponsive fluid interfaces emerge from simple feedback coupling.

PMID- 29457613
TI  - On the photocatalytic cycle of water splitting with small manganese oxides and
      the roles of water clusters as direct sources of oxygen molecules.
AB  - We theoretically studied the chemical principles behind the photodynamics of
      water splitting: 2H2O + 4hnu + M -> 4H+ + 4e- + O2 + M. To comprehend this simple
      looking but very complicated reaction, the mechanisms of at least three crucial
      phenomena, among others, need to be clarified, each of which is supposed to
      constitute the foundation of chemistry: (i) charge separation (4H+ + 4e-), (ii)
      the catalytic cycle for essentially the same reactions to be repeated by each of
      four photon absorptions with a catalyst M, and (iii) the generation of oxygen
      molecules of spin triplet. We have previously clarified the photodynamical
      mechanism of charge separation, which we refer to as coupled proton electron
      wavepacket transfer (CPEWT), based on the theory of nonadiabatic electron
      wavepacket dynamics [K. Yamamoto and K. Takatsuka, ChemPhysChem, 2017, 18, 537].
      CPEWT gives an idea of how charge separation can be materialized at each single
      photon absorption. Yet, this mechanism alone cannot address the above crucial
      items such as (ii) the catalytic cycle and (iii) O2 formation. In the studies of
      these fundamental processes, we constructed a possible minimal chemical system
      and perform semi-quantitative quantum chemical analyses, with which to attain
      insights about the possible mechanisms of photochemical water splitting. The
      present study has been inspired by the idea underlying the so-called Kok cycle,
      although we do not aim to simulate photosystem II in biological systems in
      nature. For instance, we assume here that a catalyst M (actually simple manganese
      oxides in this particular study) is pumped up to its excited states leading to
      charge separation by four-time photon absorption, each excitation of which
      triggers individual series of chemical reactions including the reorganization of
      the hydrogen-bonding network (cluster) of water molecules surrounding the
      photocatalytic center. It is shown that in the successive processes of
      restructuring of the relevant water cluster, the O[double bond, length as m
      dash]O bond is formed and consequently an oxygen molecule of spin triplet can be
      isolated within a range of a given photon energy of about 3.0 eV.

PMID- 29457614
TI  - Poly(trimethylene carbonate) and poly(D,L-lactic acid) modify human dendritic
      cell responses to staphylococci but do not affect Th1 and Th2 cell development.
AB  - Biomaterial-associated infections (BAIs) are frequent complications in the use of
      medical devices (biomaterials) correlated with considerable patient discomfort
      and high treatment costs. The presence of a biomaterial in the host causes
      derangement of local immune responses increasing susceptibility to infection.
      Dendritic cells (DCs) have an important role in directing the nature of immune
      responses by activating and controlling CD4+ T helper (Th) cell responses. To
      assess the immunomodulatory effect of the combined presence of biomaterials and
      Staphylococcus aureus (S. aureus) or Staphylococcus epidermidis (S. epidermidis),
      DC-mediated T cell proliferation and Th1/Th2 cell development were measured using
      an in vitro human cell system. Poly(trimethylene carbonate) (PTMC) and poly(D,L
      lactic acid) (PDLLA) modified the production of the DC pro-inflammatory cytokines
      TNF-alpha, IL-6 and IL-23 in response to S. aureus and S. epidermidis. However,
      this modified cytokine production did not cause differences in Th1/Th2 cell
      polarisation, showing a Th1 cell predominance. In the absence of staphylococci,
      neither of the biomaterials induced DC-mediated T cell proliferation or Th1/Th2
      cell polarisation. Moreover, either in the absence or presence of the
      biomaterials, S. aureus was a more potent inducer of DC cytokine secretion, T
      cell proliferation and Th1 cell development than S. epidermidis. In conclusion,
      although PTMC and PDLLA modulated DC cytokine responses to staphylococci, this
      did not alter the resulting Th cell development. This result suggested that, in
      this human cell model, Th1/Th2 cell responses were mainly determined by the
      species of bacteria and that PTMC or PDLLA did not detectably influence these
      responses.

PMID- 29457615
TI  - [2017 ESC Guidelines for the management of acute myocardial infarction in
      patients presenting with ST-segment elevation.]

PMID- 29457616
TI  - Successful pulmonary homograft re-implantation after previous surgical and
      percutaneous interventions.

PMID- 29457617
TI  - Fracture of the distal part of an implantable cardioverter-defibrillator lead two
      months after implantation.

PMID- 29457618
TI  - Accuracy of the lowest Pd/Pa ratio measurement during induced hyperaemia (correct
      fractional flow reserve assessment).

PMID- 29457619
TI  - Appropriate and effective interventions of subcutaneous implantable cardioverter
      defibrillator (S-ICD): single-academic-centre experience.

PMID- 29457620
TI  - First-in-man percutaneous pulmonary vein isolation enhanced by augmented reality
      system.

PMID- 29457621
TI  - Usefulness of CorMatrix-based tricuspid valve repair in the treatment of
      infective endocarditis.

PMID- 29457622
TI  - Drug-eluting stent implantation for subclavian artery reocclusion after bare
      metal stent implantation: two-year outcomes.

PMID- 29457623
TI  - Severe aortic regurgitation caused by unicuspid aortic valve.

PMID- 29457624
TI  - [Coordinated heart failure care in Poland: towards optimal organisation of the
      health care system].
AB  - Heart failure has becoming an increasing medical, economic, and social problem
      globally. The prevalence of this syndrome is rising, and despite unequivocal
      positive effects of modern therapy, reduction of mortality has been achieved at
      the cost of more frequent hospitalisations. Unlike in many European countries, in
      Poland heart failure is usually recognised later, at a more advanced stage of the
      disease, leaving less time for ambulatory treatment and resulting in a high
      number of hospitalisations. The current paper presents the most important data
      regarding morbidity and mortality due to heart failure in Poland. The experts in
      the field focus on the key source of high costs of therapy and highlight several
      critical organisational deficits present in the Polish health care system. This
      background information builds a basis for a concept of coordinated care for
      patients with heart failure. The paper discusses the fundamental elements of the
      system of coordinated care for patients with heart failure necessary to enhance
      the diagnosis, improve therapeutic effects, and reduce medical, economic, and
      social costs.

PMID- 29457625
TI  - [Transthoracic echocardiography in adults - guidelines of the Working Group on
      Echocardiography of the Polish Cardiac Society].
AB  - This document presents current Polish guidelines on the clinical use of
      transthoracic echocardiography, including stress examinations, in adult patients.
      The examinations with pocket-size imaging devices are also discussed. The authors
      present recommendations regarding indications and contraindications, staff and
      equipment requirements, patient preparation and information, examination
      protocol, reporting and reimbursement.

PMID- 29457626
TI  - [Transesophageal echocardiography in adults - guidelines of the Working Group on
      Echocardiography of the Polish Cardiac Society].
AB  - This document presents current Polish guidelines on the clinical use of
      transesophageal echocardiography, including guidance of percutaneous procedures
      and intraoperative echocardiography, in adult patients. The authors present
      recommendations regarding indications and contraindications, staff and equipment
      requirements, patient preparation and information, examination protocol,
      reporting and reimbursement.

PMID- 29457627
TI  - Combination pharmacotherapy for the treatment of fibromyalgia in adults.
AB  - BACKGROUND: Fibromyalgia is a chronic widespread pain condition affecting
      millions of people worldwide. Current pharmacotherapies are often ineffective and
      poorly tolerated. Combining different agents could provide superior pain relief
      and possibly also fewer side effects. OBJECTIVES: To assess the efficacy, safety,
      and tolerability of combination pharmacotherapy compared to monotherapy or
      placebo, or both, for the treatment of fibromyalgia pain in adults. SEARCH
      METHODS: We searched CENTRAL, MEDLINE, and Embase to September 2017. We also
      searched reference lists of other reviews and trials registries. SELECTION
      CRITERIA: Double-blind, randomised controlled trials comparing combinations of
      two or more drugs to placebo or other comparators, or both, for the treatment of
      fibromyalgia pain. DATA COLLECTION AND ANALYSIS: From all studies, we extracted
      data on: participant-reported pain relief of 30% or 50% or greater; patient
      global impression of clinical change (PGIC) much or very much improved or very
      much improved; any other pain-related outcome of improvement; withdrawals (lack
      of efficacy, adverse events), participants experiencing any adverse event,
      serious adverse events, and specific adverse events (e.g. somnolence and
      dizziness). The primary comparison was between combination and one or all single
      agent comparators. We also assessed the evidence using GRADE and created a
      'Summary of findings' table. MAIN RESULTS: We identified 16 studies with 1474
      participants. Three studies combined a non-steroidal anti-inflammatory drug
      (NSAID) with a benzodiazepine (306 participants); two combined amitriptyline with
      fluoxetine (89 participants); two combined amitriptyline with a different agent
      (92 participants); two combined melatonin with an antidepressant (164
      participants); one combined carisoprodol, paracetamol (acetaminophen), and
      caffeine (58 participants); one combined tramadol and paracetamol (acetaminophen)
      (315 participants); one combined malic acid and magnesium (24 participants); one
      combined a monoamine oxidase inhibitor with 5-hydroxytryptophan (200
      participants); and one combined pregabalin with duloxetine (41 participants). Six
      studies compared the combination of multiple agents with each component alone and
      with inactive placebo; three studies compared combination pharmacotherapy with
      each individual component but did not include an inactive placebo group; two
      studies compared the combination of two agents with only one of the agents alone;
      and three studies compared the combination of two or more agents only with
      inactive placebo.Heterogeneity among studies in terms of class of agents
      evaluated, specific combinations used, outcomes reported, and doses given
      prevented any meta-analysis. None of the combinations of drugs found provided
      sufficient data for analysis compared with placebo or other comparators for our
      preferred outcomes. We therefore provide a narrative description of results.
      There was no or inadequate evidence in any comparison for primary and secondary
      outcomes. Two studies only reported any primary outcomes of interest (patient
      reported pain relief of 30%, or 50%, or greater). For each 'Risk of bias' item,
      only half or fewer of studies had unequivocal low risk of bias. Small size and
      selective reporting were common as high risk of bias.Our GRADE assessment was
      therefore very low for primary outcomes of pain relief of 30% or 50% or greater,
      PGIC much or very much improved or very much improved, any pain-related outcome,
      participants experiencing any adverse event, any serious adverse event, or
      withdrawing because of an adverse event.Three studies found some evidence that
      combination pharmacotherapy reduced pain compared to monotherapy; these trials
      tested three different combinations: melatonin and amitriptyline, fluoxetine and
      amitriptyline, and pregabalin and duloxetine. Adverse events experienced by
      participants were not serious, and where they were reported (in 12 out of 16
      studies), all participants experienced them, regardless of treatment. Common
      adverse events were nausea, dizziness, somnolence, and headache. AUTHORS'
      CONCLUSIONS: There are few, large, high-quality trials comparing combination
      pharmacotherapy with monotherapy for fibromyalgia, consequently limiting evidence
      to support or refute the use of combination pharmacotherapy for fibromyalgia.

PMID- 29457628
TI  - A coupled in vitro/in vivo approach for engineering a heterologous type III PKS
      to enhance polyketide biosynthesis in Saccharomyces cerevisiae.
AB  - Polyketides are attractive compounds for uses ranging from biorenewable chemical
      precursors to high-value therapeutics. In many cases, synthesis in a heterologous
      host is required to produce these compounds in industrially relevant quantities.
      The type III polyketide synthase 2-pyrone synthase (2-PS) from Gerbera hybrida
      was used for the production of triacetic acid lactone (TAL) in Saccharomyces
      cerevisiae. Initial in vitro characterization of 2-PS led to the identification
      of active site variants with improved kinetic properties relative to wildtype.
      Further in vivo evaluation in S. cerevisiae suggested certain 2-PS mutations
      altered enzyme stability during fermentation. In vivo experiments also revealed
      beneficial cysteine to serine mutations that were not initially explored due to
      their distance from the active site of 2-PS, leading to the design of additional
      2-PS enzymes. While these variants showed varying catalytic efficiencies in
      vitro, they exhibited up to 2.5-fold increases in TAL production when expressed
      in S. cerevisiae. Coupling of the 2-PS variant [C35S,C372S] to an engineered S.
      cerevisiae strain led to over 10 g/L TAL at 38% of theoretical yield following
      fed-batch fermentation, the highest reported to date. Our studies demonstrate the
      success of a coupled in vitro/in vivo approach to engineering enzymes and provide
      insight on cysteine-rich enzymes and design principles toward their use in non
      native microbial hosts.

PMID- 29457629
TI  - Antibody glycoengineering strategies in mammalian cells.
AB  - As a key parameter impacting functional and structural heterogeneity, protein
      glycosylation is a critical quality attribute for antibody biotherapeutic
      manufacturing. The glycan patterns on recombinant antibodies, particularly on the
      conserved fragment crystallizable (Fc) region, can have significant effects on an
      antibody's functional activities including clearance rate, antibody-dependent
      cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and anti
      inflammatory activity. In this review, we examined specific glycan attachments
      (fucosylation, sialylation, galactosylation, high-mannose, and bisecting glycans)
      and their importance to antibody properties. Next, we summarized the recent and
      current achievements on controlling antibody glycoforms in Chinese hamster ovary
      (CHO) and other mammalian cells through multiple strategies including genetic
      engineering, protein engineering, media modification, and other emerging
      technologies. Further, the impact of one carbohydrate modification on other
      glycan structures is also described. Finally, approaches to generate desirable
      homogenous glycan profiles on antibodies are also detailed. By applying multiple
      complementary intracellular and extracellular strategies, biotechnologists are
      well on their ways to precisely tuning antibody glycoforms emerging from
      bioreactors in the coming decades.

PMID- 29457630
TI  - Combination drug delivery via multilamellar vesicles enables targeting of tumor
      cells and tumor vasculature.
AB  - Blood vessel development is critical for the continued growth and progression of
      solid tumors and, therefore, makes an attractive target for improving cancer
      therapy. Indeed, vascular-targeted therapies have been extensively explored but
      they have shown minimal efficacy as monotherapies. Combretastatin A4 (CA-4) is a
      tubulin-binding vascular disrupting agent that selectively targets the
      established tumor endothelium, causing rapid vascular beak down. Despite its
      potent anticancer potential, the drug has dose-limiting side effects,
      particularly in the form of cardiovascular toxicity. Furthermore, its poor
      aqueous solubility and the resulting limited bioavailability hinder its antitumor
      activity in the clinic. To improve the therapeutic efficacy of CA-4, we
      investigated its application as a combination therapy with doxorubicin (Dox) in a
      tumor vasculature targeted delivery vehicle: peptide-modified cross-linked
      multilamellar liposomal vesicles (cMLVs). In vitro cell culture studies showed
      that a tumor vasculature-targeting peptide, RIF7, could facilitate higher
      cellular uptake of drug-loaded cMLVs, and consequently enhance the antitumor
      efficacy in both drug resistant B16 mouse melanoma and human MDA-MB-231 breast
      cancer cells. In vivo, upon intravenous injection, targeted cMLVs could
      efficiently deliver both Dox and CA-4 to significantly slow tumor growth through
      the specific interaction of the targeting peptide with its receptor on the
      surface of tumor vasculature. This study demonstrates the potential of our novel
      targeted combination therapy delivery vehicle to improve the outcome of cancer
      treatment.

PMID- 29457631
TI  - Non-invasive genetic censusing and monitoring of primate populations.
AB  - Knowing the density or abundance of primate populations is essential for their
      conservation management and contextualizing socio-demographic and behavioral
      observations. When direct counts of animals are not possible, genetic analysis of
      non-invasive samples collected from wildlife populations allows estimates of
      population size with higher accuracy and precision than is possible using
      indirect signs. Furthermore, in contrast to traditional indirect survey methods,
      prolonged or periodic genetic sampling across months or years enables inference
      of group membership, movement, dynamics, and some kin relationships. Data may
      also be used to estimate sex ratios, sex differences in dispersal distances, and
      detect gene flow among locations. Recent advances in capture-recapture models
      have further improved the precision of population estimates derived from non
      invasive samples. Simulations using these methods have shown that the confidence
      interval of point estimates includes the true population size when assumptions of
      the models are met, and therefore this range of population size minima and maxima
      should be emphasized in population monitoring studies. Innovations such as the
      use of sniffer dogs or anti-poaching patrols for sample collection are important
      to ensure adequate sampling, and the expected development of efficient and cost
      effective genotyping by sequencing methods for DNAs derived from non-invasive
      samples will automate and speed analyses.

PMID- 29457632
TI  - Rapid eradication of bacterial phytopathogens by atmospheric pressure glow
      discharge generated in contact with a flowing liquid cathode.
AB  - Diseases caused by phytopathogenic bacteria are responsible for significant
      economic losses, and these bacteria spread through diverse pathways including
      waterways and industrial wastes. It is therefore of high interest to develop
      potent methods for their eradication. Here, antibacterial properties of direct
      current atmospheric pressure glow discharge (dc-APGD) generated in contact with
      flowing bacterial suspensions were examined against five species of
      phytopathogens. Complete eradication of Clavibacter michiganensis subsp.
      sepedonicus, Dickeya solani, and Xanthomonas campestris pv. campestris from
      suspensions of OD600  ~ 0.1 was observed, while there was at least 3.43
      logarithmic reduction in population densities of Pectobacterium atrosepticum and
      Pectobacterium carotovorum subsp. carotovorum. Analysis of plasma-chemical
      parameters of the dc-APGD system revealed its high rotational temperatures of
      2,300 +/- 100 K and 4,200 +/- 200 K, as measured from N2 and OH molecular bands,
      respectively, electron temperature of 6,050 +/- 400 K, vibrational temperature of
      4000 +/- 300 K, and high electron number density of 1.1 * 1015  cm-1 . In
      addition, plasma treatment led to formation of numerous reactive species and
      states in the treated liquid, including reactive nitrogen and oxygen species such
      as NOx , NH, H2 O2 , O2 , O, and OH. Further examination revealed that
      bactericidal activity of dc-APGD was primarily due to presence of these reactive
      species as well as to UVA, UVB, and UVC irradiation generated by the dc-APGD
      source. Plasma treatment also resulted in an increase in temperature (from 24.2
      to 40.2  degrees C) and pH (from 6.0 to 10.8) of bacterial suspensions, although
      these changes had minor effects on cell viability. All results suggest that the
      newly developed dc-APGD-based system can be successfully implemented as a simple,
      rapid, efficient, and cost-effective disinfection method for liquids originating
      from different industrial and agricultural settings.

PMID- 29457633
TI  - Binding efficiency of recombinant collagen-binding basic fibroblast growth
      factors (CBD-bFGFs) and their promotion for NIH-3T3 cell proliferation.
AB  - The recombinant basic fibroblast growth factor (bFGF) containing collagen-binding
      domain (CBD) has been found to be a potential therapeutic factor in tissue
      regeneration. However, its binding efficiency and quantification remain
      uncertain. In this research, massive recombinant bFGFs with good bioactivity for
      enhancing the proliferation of NIH-3T3 cells were achieved. An ELISA-based
      quantitative method was set up to investigate the binding efficiency of CBD-bFGFs
      on collagen films. It indicated that the CBDs significantly increased the
      collagen-binding ability of bFGF (P < .05), with the optimum binding condition
      first determined to be in the pH range of 7.5-9.5 (P < .05). Then, the relevant
      equations to calculate the binding density of bFGF, C-bFGF, and V-bFGF were
      acquired. Analysis confirmed that the bioactivity of immobilized bFGFs was well
      correlated with the density of growth factor on collagen films. Based on this
      research, the density of growth factor is a logical and applicable dosage unit
      for quantification of binding efficiency of growth factors, rather than
      traditional concentration of soluble growth factors in tissue engineering
      applications.

PMID- 29457635
TI  - Hand preference on unimanual and bimanual tasks in Barbary macaques (Macaca
      sylvanus).
AB  - The presence of group-level handedness in non-human primates remains
      controversial, as different studies have produced inconsistent results. Bimanual
      coordinated tasks have been found to elicit more pronounced hand preferences than
      simple unimanual tasks. The aim of this study was to examine manual
      lateralization in a group of 15 Barbary macaques during unimanual and bimanual
      tasks. In the unimanual task, data on simple food reaching in a foraging context
      were collected. During the bimanual task, macaques had to use one hand to hold a
      tube-shaped apparatus while reaching with the other hand to retrieve the food
      inside it. Data on the hand use to retrieve food were collected. First, no
      significant group-level hand preference was found for the unimanual task.
      However, a significant right hand bias was evident for the bimanual task. At the
      individual-level, approximately 47% and 67% of the subjects had a significant
      hand preference in the unimanual and bimanual task respectively. The strength of
      the hand preference was greater in the bimanual than in the unimanual task.
      Findings of this study add Macaca sylvanus to the other species showing a right
      hand preference for coordinated bimanual tasks. Moreover, our results add to the
      growing body of evidence that bimanual tasks are more suitable and valid measures
      to investigate handedness in non-human primates.

PMID- 29457634
TI  - "Cooperative collapse" of the denatured state revealed through Clausius-Clapeyron
      analysis of protein denaturation phase diagrams.
AB  - Protein phase diagrams have a unique potential to identify the presence of
      additional thermodynamic states even when non-2-state character is not readily
      apparent from the experimental observables used to follow protein unfolding
      transitions. Two-state analysis of the von Willebrand factor A3 domain has
      previously revealed a discrepancy in the calorimetric enthalpy obtained from
      thermal unfolding transitions as compared with Gibbs-Helmholtz analysis of free
      energies obtained from the Linear Extrapolation Method (Tischer and Auton, Prot
      Sci 2013; 22(9):1147-60). We resolve this thermodynamic conundrum using a
      Clausius-Clapeyron analysis of the urea-temperature phase diagram that defines
      how DeltaH and the urea m-value interconvert through the slope of cm versus T,
      (?cm/?T)=DeltaH/(mT) . This relationship permits the calculation of DeltaH at low
      temperature from m-values obtained through iso-thermal urea denaturation and high
      temperature m-values from DeltaH obtained through iso-urea thermal denaturation.
      Application of this equation uncovers sigmoid transitions in both cooperativity
      parameters as temperature is increased. Such residual thermal cooperativity of
      DeltaH and the m-value confirms the presence of an additional state which is
      verified to result from a cooperative phase transition between urea-expanded and
      thermally-compact denatured states. Comparison of the equilibria between expanded
      and compact denatured ensembles of disulfide-intact and carboxyamidated A3
      domains reveals that introducing a single disulfide crosslink does not affect the
      presence of the additional denatured state. It does, however, make a small
      thermodynamically favorable free energy (~-13 +/- 1 kJ/mol) contribution to the
      cooperative denatured state collapse transition as temperature is raised and urea
      concentration is lowered. The thermodynamics of this "cooperative collapse" of
      the denatured state retain significant compensations between the enthalpy and
      entropy contributions to the overall free energy.

PMID- 29457636
TI  - Human papillomavirus infection and lichen sclerosus: coincidence or link?

PMID- 29457637
TI  - Rhesus macaque personality, dominance, behavior, and health.
AB  - Previous studies of nonhuman primates have found relationships between health and
      individual differences in personality, behavior, and social status. However,
      despite knowing these factors are intercorrelated, many studies focus only on a
      single measure, for example, rank. Consequently, it is difficult to determine the
      degree to which these individual differences are independently associated with
      health. The present study sought to untangle the associations between health and
      these individual differences in rhesus macaques (Macaca mulatta). We studied 85
      socially housed macaques at the Oregon and California National Primate Research
      Centers, and used veterinary records to determine the number of injuries and
      illnesses for each macaque. We measured personality using 12 items from a well
      established primate personality questionnaire, performed focal observations of
      behaviors, and calculated dominance status from directional supplant data. All
      twelve personality questionnaire items were reliable and were used to represent
      five of the six personality dimensions identified in rhesus macaques-Dominance,
      Confidence, Openness, Anxiety, and Friendliness (also known as Sociability).
      Following this, we fit generalized linear mixed effects models to understand how
      these factors were associated with an animal's history of injury and history of
      illness. In the models, age was an offset, facility was a random effect, and the
      five personality dimensions, behavior, sex, and dominance status were fixed
      effects. Number of injuries and illnesses were each best represented by a
      negative binomial distribution. For the injury models, including the effects did
      improve model fit. This model revealed that more confident and more anxious
      macaques experienced fewer injuries. For the illness models, including the fixed
      effects did not significantly improve model fit over a model without the fixed
      effects. Future studies may seek to assess mechanisms underlying these
      associations.

PMID- 29457638
TI  - A dialectical behavior therapy skills intervention for women with suicidal
      behaviors in rural Nepal: A single-case experimental design series.
AB  - BACKGROUND: Suicide in low- and middle-income countries (LMICs) accounts for 75%
      of the world's burden of suicide mortality and is the leading single cause of
      death among Nepali reproductive age women. To advance treatment for suicidal
      behaviors in LMICs, a single-case experimental design (SCED) was conducted of a
      culturally adapted Dialectical Behavior Therapy skills intervention for Nepali
      populations (DBT-N). METHOD: Ten Nepali women with histories of suicidality
      participated in the 10-session intervention. Outcomes of emotion regulation,
      suicidal ideation, depression, anxiety, resilience, and coping skills use were
      measured at multiple time points pre-intervention, during, and at follow-up.
      Qualitative interviewing assessed DBT-N's feasibility and acceptability. RESULTS:
      Participants showed improvements in emotion regulation over the course of
      treatment, which were associated with increased skills use. Rapid, sustained
      reductions in suicidal ideation and improvements in resilience were observed
      after DBT-N initiation. CONCLUSION: This SCED supports conducting further
      evaluation of DBT-N through controlled trials with emotion regulation as a target
      mechanism of action for reducing suicidal behaviors in LMICs.

PMID- 29457639
TI  - Hepatitis E virus infection in HIV-infected patients: A large cohort study in
      Yunnan province, China.
AB  - Hepatitis E virus (HEV) infection in immunocompromised patients often results in
      distinct outcome, compared to the infection in general population. This study
      aimed to investigate the prevalence, potential risk factors, and clinical
      features of HEV infection among HIV patients treated with antiretroviral therapy
      (ART) in Yunnan province, China. A total of 770 HIV-infected patients between May
      2015 and February 2016 were enrolled in Yunnan, China. All patients received ART.
      All plasma samples were tested for anti-HEV IgG, anti-HEV IgM antibodies using
      ELISA kits, and HEV RNA by real-time qRT-PCR. Association between anti-HEV
      antibody positivity and demographic, clinical and laboratory measures was
      assessed in univariate and multivariate logistic regression models. Of the 770
      HIV-infected patients, 342 patients (44.42%) were anti-HEV IgG antibody positive,
      and six patients (0.78%) were anti-HEV IgM antibody positive. None of the
      patients was HEV RNA positive, as tested in our assays. We found that age,
      gender, CD4 cell count, WHO stage, marital status, and total cholesterol levels
      were associated with HEV infection. We report a high seroprevalence rate and
      several potential risk factors of HEV infection in a large HIV cohort from Yunnan
      province in China. Further research on identification of the circulating HEV
      strains and the clinical outcome of this patient population is required.

PMID- 29457640
TI  - Application of adaptive laboratory evolution to overcome a flux limitation in an
      Escherichia coli production strain.
AB  - Gene deletion strategies using flux balance analysis (FBA) have improved the
      growth-coupled production of various compounds. However, the productivities were
      often below the expectation because the cells failed to adapt to these genetic
      perturbations. Here, we demonstrate the productivity of the succinate of the
      designed gene deletion strain was improved by adaptive laboratory evolution
      (ALE). Although FBA predicted deletions of adhE-pykAF-gldA-pflB lead to produce
      succinate from glycerol with a yield of 0.45 C-mol/C-mol, the knockout mutant did
      not produce only 0.08 C-mol/Cmol, experimentally. After the ALE experiments, the
      highest succinate yield of an evolved strain reached to the expected value.
      Genome sequencing analysis revealed all evolved strains possessed novel mutations
      in ppc of I829S or R849S. In vitro enzymatic assay and metabolic profiling
      analysis revealed that these mutations desensitizing an allosteric inhibition by
      L-aspartate and improved the flux through Ppc, while the activity of Ppc in the
      unevolved strain was tightly regulated by L-aspartate. These result demonstrated
      that the evolved strains achieved the improvement of succinate production by
      expanding the flux space of Ppc, realizing the predicted metabolic state by FBA.

PMID- 29457641
TI  - Effects of time delays on biological feedback systems and electromagnetic field
      exposures.

PMID- 29457642
TI  - Identification and characterization of neutralization epitopes at VP2 and VP1 of
      enterovirus A71.
AB  - Enterovirus A71 (EV-A71) neutralization escape mutants were generated with
      monoclonal antibody MAB979 (Millipore). The VP2-T141I and VP1-D14N substitutions
      were identified. Using reverse genetics, infectious clones with these
      substitutions were constructed and tested by neutralization assay with immune
      sera from mice and humans. The N-terminus VP1-14 is more important than EF loop
      VP2-141 in acute human infection, mainly because it recognised IgM present in
      acute infection. The N-terminus VP1 could be a useful target for diagnostics and
      therapeutic antibodies in acute infection.

PMID- 29457643
TI  - Performing under pressure: hypertension and the regulation of cerebral oxygen
      delivery.

PMID- 29457645
TI  - Research Review: Test-retest reliability of standardized diagnostic interviews to
      assess child and adolescent psychiatric disorders: a systematic review and meta
      analysis.
AB  - BACKGROUND: A better understanding of factors contributing to the observed
      variability in estimates of test-retest reliability in published studies on
      standardized diagnostic interviews (SDI) is needed. The objectives of this
      systematic review and meta-analysis were to estimate the pooled test-retest
      reliability for parent and youth assessments of seven common disorders, and to
      examine sources of between-study heterogeneity in reliability. METHODS: Following
      a systematic review of the literature, multilevel random effects meta-analyses
      were used to analyse 202 reliability estimates (Cohen's kappa = ?) from 31
      eligible studies and 5,369 assessments of 3,344 children and youth. RESULTS:
      Pooled reliability was moderate at ? = .58 (CI 95% 0.53-0.63) and between-study
      heterogeneity was substantial (Q = 2,063 (df = 201), p < .001 and I2  = 79%). In
      subgroup analysis, reliability varied across informants for specific types of
      psychiatric disorder (? = .53-.69 for parent vs. ? = .39-.68 for youth) with
      estimates significantly higher for parents on attention deficit hyperactivity
      disorder, oppositional defiant disorder and the broad groupings of externalizing
      and any disorder. Reliability was also significantly higher in studies with
      indicators of poor or fair study methodology quality (sample size <50, retest
      interval <7 days). CONCLUSIONS: Our findings raise important questions about the
      meaningfulness of published evidence on the test-retest reliability of SDIs and
      the usefulness of these tools in both clinical and research contexts. Potential
      remedies include the introduction of standardized study and reporting
      requirements for reliability studies, and exploration of other approaches to
      assessing and classifying child and adolescent psychiatric disorder.

PMID- 29457644
TI  - Trajectories of frontal brain activity and socio-emotional development in
      children.
AB  - Asymmetric frontal brain activity is thought to reflect individual differences in
      approach- and avoidance-oriented motivation and emotional experience. Using a
      prospective longitudinal design, the authors investigated whether trajectories of
      frontal electroencephalogram (EEG) asymmetry in children (Mage  = 6.39 years at
      enrollment) predicted subjective, behavioral, and autonomic indices of
      socioemotional processes. Resting frontal EEG activity was measured across four
      separate repeated assessments spanning approximately 2 years. Children's EEG
      asymmetry across assessments was best characterized by two trajectories: a stable
      right frontal asymmetry class (48.65%), and a stable left frontal asymmetry class
      (51.35%). At visit 4, children in the stable right frontal asymmetry displayed
      more avoidance-related tendencies and children in the stable left frontal
      asymmetry class exhibited more approach-related tendencies across social,
      emotional, and autonomic measures. These findings suggest that developmental
      patterns of resting frontal brain activity across the early school years may
      underlie approach- and avoidance-related motivation and predict socio-emotional
      processes in some children.

PMID- 29457646
TI  - A reexamination of the cognitive behavioral model of chronic fatigue syndrome.
AB  - OBJECTIVE: The cognitive behavioral model of chronic fatigue syndrome (CFS)
      suggests that cognitions and reduced activity level perpetuate the fatigue and
      impairment that individuals with CFS experience. The two empirical evaluations of
      this model resulted in conflicting findings. The current study examines the
      influence of case definition fulfillment on the applicability of this model to
      CFS. METHOD: A moderated mediation analysis was conducted on 990 individuals with
      CFS to reexamine the behavioral pathway of this model. Case definition
      fulfillment was entered as a moderator. RESULTS: Findings were generally
      inconsistent with the cognitive behavioral model of CFS. Case definition
      fulfillment significantly moderated the relation between activity level and
      physical impairment (beta = -0.08, p = 0.03); individuals who met more stringent
      case definitions demonstrated a weaker relation between activity level and
      impairment. CONCLUSIONS: This model may not accurately represent the experience
      of individuals with CFS, particularly those who fulfill more stringent case
      definitions.

PMID- 29457647
TI  - Learning of hierarchical serial patterns emerges in infancy.
AB  - Recursive, hierarchically organized serial patterns provide the underlying
      structure in many cognitive and motor domains including speech, language, music,
      social interaction, and motor action. We investigated whether learning of
      hierarchical patterns emerges in infancy by habituating 204 infants to different
      hierarchical serial patterns and then testing for discrimination and
      generalization of such patterns. Results indicated that 8- to 10-month-old and 12
      to 14-month-old infants exhibited sensitivity to the difference between
      hierarchical and non-hierarchical structure but that 4- to 6-month-old infants
      did not. These findings demonstrate that the ability to perceive, learn, and
      generalize recursive, hierarchical, pattern rules emerges in infancy and add to
      growing evidence that general-purpose pattern learning mechanisms emerge during
      the first year of life.

PMID- 29457648
TI  - Reduction of infection risk mediated by co-culturing Vibrio parahaemolyticus and
      Listeria monocytogenes in refrigerated cooked shrimp.
AB  - BACKGROUND: Vibrio parahaemolyticus and Listeria monocytogenes are seafood
      pathogens of public health significance, and predictive models are effective
      tools for quantitative microbial risk assessment of these pathogens. However,
      most current predictive models are based on growth of single strains in broth
      cultures, and interactions of two or more bacteria in a food matrix can skew the
      outcomes of the predictions. Therefore, the impact of V. parahaemolyticus and L.
      monocytogenes when co-cultured and in monoculture on cooked shrimp in cold
      storage was investigated. RESULTS: The results indicated that L. monocytogenes co
      cultured with V. parahaemolyticus exhibited reduced growth and longer lag phase
      at 4  degrees C and 10  degrees C. V. parahaemolyticus exhibited similar behavior
      when co-cultured with L. monocytogenes at 4  degrees C (death rate K =  - 0.67
      log10 CFU g-1 day . The death rate K at 10  degrees C when V. parahaemolyticus co
      cultured with L. monocytogenes was -1.62 log10 CFU g-1 day-1 . There was no
      significant reduction of growth in monoculture experiments. CONCLUSION: This
      study has revealed that interaction of V. parahaemolyticus and L. monocytogenes
      should be considered when quantifying risks posed by these pathogens during
      consumption of seafood products. (c) 2018 Society of Chemical Industry.

PMID- 29457649
TI  - When trichoscopy enlightens clinics: more about discoid lupus.

PMID- 29457650
TI  - Effects of applying oil-extracted microalgae on the fermentation quality, feed
      nutritive value and aerobic stability of ensiled sweet sorghum.
AB  - BACKGROUND: A laboratory-silo study was conducted to evaluate the fermentation
      quality, feed-nutritive value and aerobic stability of sweet sorghum silage with
      or without oil-extracted microalgae supplementation. Sweet sorghum was mixed with
      four microalgae levels (0%, 1%, 2% and 3% on a dry matter basis; control, M1, M2
      and M3, respectively) and ensiled for 45 d. Further, the four experimental
      silages were subjected to an aerobic stability test lasting 7 d. RESULTS: All the
      silages except M3 silage had good fermentative characteristics with low pH and
      ammonia nitrogen concentrations, and high lactic acid concentrations and
      favorable microbial parameters. Meanwhile, oil-extracted microalgae
      supplementation improved the feed-nutritional value of sweet sorghum silage.
      Fibre (neutral detergent fibre, acid detergent fibre, acid detergent lignin and
      cellulose) concentrations decreased, while dry matter and crude protein levels
      markedly increased (P < 0.05). Compared with the control (69.7 h), treatments M2
      and M3 improved the aerobic stability of sweet sorghum silage by 43.8% and more
      than 143% respectively, and decreased the clostridia spore counts during the
      stage of air exposure. CONCLUSION: Sweet sorghum silage produced with 2% oil
      extracted microalgae addition was the most suitable for animal use due to the
      optimal balance of fermentation quality, feed-nutritional value and aerobic
      stability, which merits further in vivo studies using grazing ruminants. (c) 2018
      Society of Chemical Industry.

PMID- 29457652
TI  - Expanding the histopathological spectrum of CFL2-related myopathies.
AB  - Congenital myopathies (CMs) caused by mutation in cofilin-2 gene (CFL2) show
      phenotypic heterogeneity ranging from early-onset and rapid progressive forms to
      milder myopathy. Muscle histology is also heterogeneous showing rods and/or
      myofibrillar changes. Here, we report on three new cases, from two unrelated
      families, of severe CM related to novel homozygous or compound heterozygous loss
      of-function mutations in CFL2. Peculiar histopathological changes showed nemaline
      bodies and thin filaments accumulations together to myofibrillar changes, which
      were evocative of the muscle findings observed in Cfl2-/- knockout mouse model.

PMID- 29457651
TI  - Progressive recruitment of contralesional cortico-reticulospinal pathways drives
      motor impairment post stroke.
AB  - KEY POINTS: Activation of the shoulder abductor muscles in the arm opposite a
      unilateral brain injury causes involuntary increases in elbow, wrist and finger
      flexion in the same arm, a phenomenon referred to as the flexion synergy. It has
      been proposed that flexion synergy expression is related to reduced output from
      ipsilesional motor cortex and corticospinal pathways. In this human subjects
      study, we provide evidence that the magnitude of flexion synergy expression is
      instead related to a progressive, task-dependent recruitment of contralesional
      cortex. We also provide evidence that recruitment of contralesional cortex may
      induce excessive activation of ipsilateral reticulospinal descending motor
      pathways that cannot produce discrete movements, leading to flexion synergy
      expression. We interpret these findings as an adaptive strategy that preserves
      low-level motor control at the cost of fine motor control. ABSTRACT: A hallmark
      of hemiparetic stroke is the loss of fine motor control in the contralesional arm
      and hand and the constraint to a grouped movement pattern known as the flexion
      synergy. In the flexion synergy, increasing shoulder abductor activation drives
      progressive, involuntary increases in elbow, wrist and finger flexion. The neural
      mechanisms underlying this phenomenon remain unclear. Here, across 25 adults with
      moderate to severe hemiparesis following chronic stroke and 18 adults without
      neurological injury, we test the overall hypothesis that two inter-related
      mechanisms are necessary for flexion synergy expression: increased task-dependent
      activation of the intact, contralesional cortex and recruitment of contralesional
      motor pathways via ipsilateral reticulospinal projections. First, we imaged brain
      activation in real time during reaching motions progressively constrained by
      flexion synergy expression. Using this approach, we found that cortical activity
      indeed shifts towards the contralesional hemisphere in direct proportion to the
      degree of shoulder abduction loading in the contralesional arm. We then leveraged
      the post-stroke reemergence of a developmental brainstem reflex to show that
      anatomically diffuse reticulospinal motor pathways are active during synergy
      expression. We interpret this progressive recruitment of contralesional cortico
      reticulospinal pathways as an adaptive strategy that preserves low-level motor
      control at the cost of fine motor control.

PMID- 29457653
TI  - How to Create Shared Symbols.
AB  - Human cognition and behavior are dominated by symbol use. This paper examines the
      social learning strategies that give rise to symbolic communication. Experiment 1
      contrasts an individual-level account, based on observational learning and
      cognitive bias, with an inter-individual account, based on social coordinative
      learning. Participants played a referential communication game in which they
      tried to communicate a range of recurring meanings to a partner by drawing, but
      without using their conventional language. Individual-level learning, via
      observation and cognitive bias, was sufficient to produce signs that became
      increasingly effective, efficient, and shared over games. However, breaking a
      referential precedent eliminated these benefits. The most effective, most
      efficient, and most shared signs arose when participants could directly interact
      with their partner, indicating that social coordinative learning is important to
      the creation of shared symbols. Experiment 2 investigated the contribution of two
      distinct aspects of social interaction: behavior alignment and concurrent partner
      feedback. Each played a complementary role in the creation of shared symbols:
      Behavior alignment primarily drove communication effectiveness, and partner
      feedback primarily drove the efficiency of the evolved signs. In conclusion,
      inter-individual social coordinative learning is important to the evolution of
      effective, efficient, and shared symbols.

PMID- 29457654
TI  - Chemoselective Glycosylation of Peptides through S-Alkylation Reaction.
AB  - An efficient and rapid procedure for synthesizing S-linked glycopeptides is
      reported. The approach uses activated molecular sieves as a base to promote the
      selective S-alkylation of readily prepared cysteine-containing peptides, upon
      reaction of appropriate glycosyl halides. Considering the very mild conditions
      employed, the chemoselective linkage of the electrophilic sugar with a peptide
      sulfhydryl group occurred in satisfactory yield, allowing the incorporation of
      mono and disaccharide moieties. The sugar-peptide conjugates obtained from alpha
      d-glycosyl derivatives adopt a beta-S-configuration, indicating the high
      stereoselectivity of the substitution reaction.

PMID- 29457655
TI  - Importance of growth rate on mercury and polychlorinated biphenyl bioaccumulation
      in fish.
AB  - To evaluate the effect of fish growth on mercury (Hg) and polychlorinated
      biphenyl (PCB) bioaccumulation, a non-steady-state toxicokinetic model, combined
      with a Wisconsin bioenergetics model, was developed to simulate Hg and PCB
      bioaccumulation in bluegill (Lepomis macrochirus). The model was validated by
      comparing observed with predicted Hg and PCB 180 concentrations across 5 age
      classes from 5 different waterbodies across North America. The non-steady-state
      model generated accurate predictions for Hg and PCB bioaccumulation in 3 of 5
      waterbodies: Apsey Lake (ON, Canada), Sharbot Lake (ON, Canada), and Stonelick
      Lake (OH, USA). The poor performance of the model for the Detroit River (MI,
      USA/ON, Canada) and Lake Hartwell (GA/SC, USA), which are 2 well-known
      contaminated sites with possibly high heterogeneity in spatial contamination, was
      attributed to changes in feeding behavior and/or prey contamination. Model
      simulations indicate that growth dilution is a major component of contaminant
      bioaccumulation patterns in fish, especially during early life stages, and was
      predicted to be more important for hydrophobic PCBs than for Hg. Simulations that
      considered tissue-specific growth provided some improvement in model performance
      particularly for PCBs in fish populations that exhibited changes in their whole
      body lipid content with age. Higher variation in lipid growth compared with that
      of lean dry protein was also observed between different bluegill populations,
      which partially explains the greater variation in PCB bioaccumulation slopes
      compared with Hg across sampling sites. Environ Toxicol Chem 2018;37:1655-1667.
      (c) 2018 SETAC.

PMID- 29457656
TI  - Fatty acid binding protein deletion prevents stress-induced preference for
      cocaine and dampens stress-induced corticosterone levels.
AB  - Genetic and pharmacological manipulation of endocannabinoid (eCB) signaling has
      previously been shown to have an important role on the rewarding properties of
      drugs of abuse, including cocaine. Recently, fatty acid binding proteins (FABPs)
      have been proposed as intracellular transporters of the endocannabinoid
      anandamide (AEA) as well as other bioactive lipids to their catabolic enzyme,
      fatty acid amide hydrolase (FAAH). The role of these transporters in modulating
      the brains reward system has yet to be investigated. This study examined the
      effects of genetic deletion of FABP 5/7 on cocaine preference, as assessed by the
      Conditioned Place Preference (CPP) paradigm. Male and female wild type (WT) and
      FABP 5/7 KO mice showed similar acquisition of cocaine CPP, with no differences
      found in overall locomotor activity. In addition, while male and female WT mice
      showed stress-induced CPP for cocaine, male and female FABP 5/7 KO mice failed to
      show a stress-induced preference for the cocaine-paired chamber. Additionally,
      serum corticosterone levels were analyzed to explore any potential differences in
      stress response that may be responsible for the lack of stress-induced preference
      for cocaine. Serum samples were obtained in animals under basal conditions as
      well as following a 30-min tube restraint stress. Male and female FABP 5/7 KO
      mice showed reduced corticosterone levels under stress compared to their WT
      counterparts. The reduction in corticosterone response under stress may mediate
      that lack of a stress-induced preference for cocaine in the FABP 5/7 KO mice.
      Thus, the role of FABPs may play an important role in drug-seeking behavior under
      stressful conditions.

PMID- 29457657
TI  - Semaphorin4A and H-ferritin utilize Tim-1 on human oligodendrocytes: A novel
      neuro-immune axis.
AB  - Deficiency of trophic factors relating to the survival of oligodendrocytes,
      combined with direct interactions with the immune system, are favored paradigms
      that are increasingly implicated in demyelinating diseases of the central nervous
      system. We and others have previously shown that Sema4A and H-ferritin interact
      through the T-cell immunoglobulin and mucin domain (Tim-2) receptor in mice. H
      ferritin has been identified as the iron delivery protein for oligodendrocytes,
      whereas Sema4A causes a direct cytotoxic effect. However, the expression of Tim-2
      has not been detected in humans. Here, we demonstrate that, similar to rodents,
      human oligodendrocytes undergo apoptosis when exposed to Sema4A and take up H
      ferritin for meeting iron requirements and that these functions are mediated via
      the Tim-1 receptor. Moreover, we also demonstrate the ability of H-ferritin to
      block Sema4A-mediated cytotoxicity. Furthermore, we show in a series of pilot
      studies that Sema4A is detectable in the CSF of multiple sclerosis patients and
      HIV-seropositive persons and can induce oligodendrocyte cell death. Together,
      these results identify a novel iron uptake mechanism for human oligodendrocytes
      and a connection between oligodendrocytes and the immune system.

PMID- 29457658
TI  - Decreased SCIN expression, associated with promoter methylation, is a valuable
      predictor for prognosis in acute myeloid leukemia.
AB  - The present study was aimed to investigate SCIN expression as well as promoter
      methylation and further explore their clinical relevance in acute myeloid
      leukemia (AML) patients. Real-time quantitative PCR was carried out to detect the
      expression level of SCIN in 119 AML patients and 37 healthy controls. Real-time
      quantitative methylation-specific PCR and bisulfite sequencing PCR were carried
      out to detect SCIN promoter methylation levels in 103 AML patients and 29
      controls. As compared with controls, the level of SCIN transcript was
      significantly down-regulated in AML patients (P = 0.001), and the level of
      methylated SCIN promoter was significantly higher in AML patients (P = 0.001).
      Moreover, the level of promoter methylation was weakly negatively correlated with
      SCIN expression in AML patients (R = -0.265, P = 0.027). Demethylation of SCIN
      promoter by 5-aza-2'-deoxycytidine could restore its expression in leukemic cell
      line THP1. The age of SCINlow patients was significantly higher and C/EBPA
      mutation was significantly less than SCINhigh patients (P = 0.039 and 0.038,
      respectively). Moreover, the rate of complete remission (CR) of SCINlow patients
      was significantly lower than SCINhigh patients (P = 0.009). Kaplan-Meier analysis
      showed that low SCIN expression was associated with shorter overall survival (P =
      0.036). Cox regression analysis demonstrated low SCIN expression was an
      independent poor prognostic factor (P = 0.047). Furthermore, SCIN expression was
      restored in those patients who achieved CR after induction therapy (P = 0.003).
      These findings indicate that decreased SCIN expression associated with its
      promoter methylation is a valuable biomarker for predicting adverse prognosis in
      AML patients.

PMID- 29457659
TI  - Improved production, purification, and characterization of biosurfactants
      produced by Serratia marcescens SM3 and its isogenic SMRG-5 strain.
AB  - In this study, the biosurfactants (Bs) production of two Serratia marcescens
      strains (SM3 and its isogenic SMRG-5 strain) was improved and the tenso-active
      agents were purified and characterized. A 23 factorial design was used to
      evaluate the effect of nitrogen and carbon sources on the surface tension (ST)
      reduction and emulsion index (EI24 ) of the produced Bs. Optimum Bs production by
      SM3 was achieved at high concentrations of carbon and nitrogen, reducing ST to
      26.5 +/- 0.28 dynes/cm, with an EI24 of 79.9 +/- 0.2%. Meanwhile, the best
      results for SMRG-5 were obtained at low concentrations, reducing the ST to 25.2
      +/- 0.2 dynes/cm, with an EI24 of 89.7 +/- 0.28%. The optimal conditions for Bs
      production were scaled up in a 2-L reactor, yielding 4.8 and 5.2 g/L for SM3 and
      SMRG-5, respectively. Gas Chromatography-Mass Spectrometry (GC-MS) analysis
      revealed the presence of two different lipopeptides (hidrofobic fractions:
      octadecanoic and hexadecanoic acid for SM3 and SMRG5, respectively). Both strains
      were capable of benzo [a] pyrene removal (59% after 72 H of culture).

PMID- 29457660
TI  - Prevalence of orofacial clefts and risks for nonsyndromic cleft lip with or
      without cleft palate in newborns at a university hospital from West Mexico.
AB  - We determined the overall prevalence of typical orofacial clefts and the
      potential risks for nonsyndromic cleft lip with or without cleft palate in a
      university hospital from West Mexico. For the prevalence, 227 liveborn infants
      with typical orofacial clefts were included from a total of 81,193 births
      occurred during the period 2009-2016 at the "Dr. Juan I. Menchaca" Civil Hospital
      of Guadalajara (Guadalajara, Jalisco, Mexico). To evaluate potential risks, a
      case-control study was conducted among 420 newborns, including only those 105
      patients with nonsyndromic cleft lip with or without cleft palate (cases), and
      315 infants without birth defects (controls). Data were analyzed using
      multivariable logistic regression analysis expressed as adjusted odds ratio with
      95% confidence intervals . The overall prevalence for typical orofacial clefts
      was 28 per 10,000 (95% confidence interval: 24.3-31.6), or 1 per 358 live births.
      The mean values for the prepregnancy weight, antepartum weight, and pre-pregnancy
      body mass index were statistically higher among the mothers of cases. Infants
      with nonsyndromic cleft lip with or without cleft palate had a significantly
      higher risk for previous history of any type of congenital anomaly (adjusted odds
      ratio: 2.7; 95% confidence interval: 1.4-5.1), history of a relative with cleft
      lip with or without cleft palate (adjusted odds ratio: 19.6; 95% confidence
      interval: 8.2-47.1), and first-trimester exposures to progestogens (adjusted odds
      ratio: 6.8; 95% CI 1.8-25.3), hyperthermia (adjusted odds ratio: 3.4; 95%
      confidence interval: 1.1-10.6), and common cold (adjusted odds ratio: 3.6; 95%
      confidence interval: 1.1-11.9). These risks could have contributed to explain the
      high prevalence of orofacial clefts in our region of Mexico, emphasizing that
      except for history of relatives with cleft lip with or without cleft palate, most
      are susceptible of modification.

PMID- 29457662
TI  - Efficient Catalytic Enantioselective Hydroxyamination of alpha-Aryl-alpha
      Cyanoacetates with 2-Nitrosopyridines.
AB  - The highly enantioselective totally N-selective hydroxyamination reaction of
      alpha-aryl-alpha-cyanoacetates with 2-nitrosopyridines was realized by using a
      chiral N,N'-dioxide/Mg(OTf)2 complex as catalyst, which enriches the nitroso
      chemistry. A variety of 2-cyano-2-[hydroxyl(pyrydin-2-yl)amino]acetates with
      quaternary stereocenters and potential antibacterial activities were obtained in
      excellent yields with good to excellent ee values under as low as 0.05 mol %
      catalyst loading. The products could be easily transformed to useful alpha-amino
      amides and 1,2-diamines. Besides, a possible transition state model was proposed
      to elucidate the origin of the chirality induction.

PMID- 29457661
TI  - Analysis of 13 C and 14 C labeling in pyruvate and lactate in tumor and blood of
      lymphoma-bearing mice injected with 13 C- and 14 C-labeled pyruvate.
AB  - Measurements of hyperpolarized 13 C label exchange between injected [1-13
      C]pyruvate and the endogenous tumor lactate pool can give an apparent first-order
      rate constant for the exchange. The determination of the isotope flux, however,
      requires an estimate of the labeled pyruvate concentration in the tumor. This was
      achieved here by measurement of the tumor uptake of [1-14 C]pyruvate, which
      showed that <2% of the injected pyruvate reached the tumor site. Multiplication
      of this estimated labeled pyruvate concentration in the tumor with the apparent
      first-order rate constant for hyperpolarized 13 C label exchange gave an isotope
      flux that showed good agreement with a flux determined directly by the injection
      of non-polarized [3-13 C]pyruvate, rapid excision of the tumor after 30 s and
      measurement of 13 C-labeled lactate concentrations in tumor extracts. The
      distribution of labeled lactate between intra- and extracellular compartments and
      the blood pool was investigated by imaging, by measurement of the labeled lactate
      concentration in blood and tumor, and by examination of the effects of a
      gadolinium contrast agent and a lactate transport inhibitor on the intensity of
      the hyperpolarized [1-13 C]lactate signal. These measurements showed that there
      was significant export of labeled lactate from the tumor, but that labeled
      lactate in the blood pool produced by the injection of hyperpolarized [1-13
      C]pyruvate showed only relatively low levels of polarization. This study shows
      that measurements of hyperpolarized 13 C label exchange between pyruvate and
      lactate in a murine tumor model can provide an estimate of the true isotope flux
      if the concentration of labeled pyruvate that reaches the tumor can be
      determined.

PMID- 29457663
TI  - Tandem Functionalization in a Highly Branched Polymer with Layered Structure.
AB  - A hyperbranched polymer with multilayer structure was developed to demonstrate
      the possibility of highly efficient tandem functionalization reactions at
      different domains within one nanostructured platform. The polymer scaffold was
      constructed by chain-growth copper-catalyzed azide-alkyne cycloaddition
      polymerization of three functional monomers with sequential monomer addition in
      one pot. Subsequent reactions with different monomer units resulted in efficient
      functionalization of each segment with construction of a highly sophisticated
      polymer structure by a robust procedure. As a proof of concept, the ability of
      this polymer structure to quantitatively load six species of guest molecules
      through three different types of conjugation reactions was demonstrated.

PMID- 29457664
TI  - Production and Structural Analysis of Membrane-Anchored Proteins in Phospholipid
      Nanodiscs.
AB  - Structural studies on membrane-anchored proteins containing a transmembrane (TM)
      helix have been hampered by difficulties in producing these proteins in a
      natively folded form. Detergents that are required to solubilize the hydrophobic
      TM helix usually destabilize the soluble domain. Thus, TM helices are removed for
      structural studies, which neglects the pivotal role of a membrane on protein
      function. This work presents a versatile strategy for the production of this
      protein class attached to phospholipid nanodiscs. By inserting the TM-helix into
      nanodiscs and a subsequent SortaseA-mediated ligation of the soluble domain,
      membrane-anchored BclxL could be obtained in a folded conformation. This strategy
      is suitable for high-resolution structure determination as well as for probing
      membrane location by NMR. This method will be applicable to a wide range of
      membrane-anchored proteins and will be useful to decipher their functional role
      in a native membrane environment.

PMID- 29457666
TI  - The in vivo effects of cefazolin, cefuroxime, and cefoperazon on the carbonic
      anhydrase in different rat tissues.
AB  - In this paper, the in vivo effects of some antibiotics including cefazolin,
      cefuroxime, and cefoperazon, on the activity of the carbonic anhydrase enzyme
      (CA) in heart, brain, eye, liver, and kidney tissues of rats were evaluated. For
      this purpose, 16 different groups, which each containing six rats (n = 6), were
      formed (control group, cefazolin groups, cefuroxime groups, and cefoperazon
      groups). The rats were necropsied 60 min after the intraperitoneal injection of
      the chemicals into the rats. The CA activities were measured for each tissue
      using esterase activity methods. The activity values for each tissue obtained
      were statistically calculated. The CA activities in the liver tissue were
      assessed, and the activities of the cefoperazon groups were decreased compared to
      the sham groups from the third hour (p < 0.05). In the cefuroxime and cefoperazon
      groups, the CA activities in the eye tissue were decreased during the first 3 h
      and then increased (p < 0.05).

PMID- 29457665
TI  - Comparative analysis of lipid-mediated CRISPR-Cas9 genome editing techniques.
AB  - CRISPR-Cas technology has revolutionized genome engineering. While Cas9 was not
      the first programmable endonuclease identified, its simplicity of use has driven
      widespread adoption in a short period of time. While CRISPR-Cas genome editing
      holds enormous potential for clinical applications, its use in laboratory
      settings for genotype-phenotype studies and genome-wide screens has led to
      breakthroughs in the understanding of many molecular pathways. Numerous protocols
      have been described for introducing CRISPR-Cas components into cells, and here we
      sought to simplify and optimize a protocol for genome editing using readily
      available and inexpensive tools. We compared plasmid, ribonucleoprotein (RNP),
      and RNA transfection to determine which was method was most optimal for editing
      cells in a laboratory setting. We limited our comparison to lipofection-mediated
      introduction because the reagents are widely available. To facilitate
      optimization, we developed a novel reporter assay to measure gene disruption and
      the introduction of a variety of exogenous DNA tags. Each method efficiently
      disrupted endogenous genes and was able to stimulate the introduction of foreign
      DNA at specific sites, albeit to varying efficiencies. RNP transfection produced
      the highest level of gene disruption and was the most rapid and efficient method
      overall. Finally, we show that very short homology arms of 30 base pairs can
      mediate site-specific editing. The methods described here should broaden the
      accessibility of RNP-mediated lipofection for laboratory genome-editing
      experiments.

PMID- 29457667
TI  - Synthesis and discovery of potent carbonic anhydrase, acetylcholinesterase,
      butyrylcholinesterase, and alpha-glycosidase enzymes inhibitors: The novel N,N'
      bis-cyanomethylamine and alkoxymethylamine derivatives.
AB  - During this investigation, N,N'-bis-azidomethylamines, N,N'-bis-cyanomethylamine,
      new alkoxymethylamine and chiral derivatives, which are considered to be a new
      generation of multifunctional compounds, were synthesized, functional properties
      were investigated, and anticholinergic and antidiabetic properties of those
      compounds were studied through the laboratory tests, and it was approved that
      they contain physiologically active compounds rather than analogues. Novel N-bis
      cyanomethylamine and alkoxymethylamine derivatives were effective inhibitors of
      the alpha-glycosidase, cytosolic carbonic anhydrase I and II isoforms,
      butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) with Ki values in
      the range of 0.15-13.31 nM for alpha-glycosidase, 2.77-15.30 nM for human
      carbonic anhydrase isoenzymes I (hCA I), 3.12-21.90 nM for human carbonic
      anhydrase isoenzymes II (hCA II), 23.33-73.23 nM for AChE, and 3.84-48.41 nM for
      BChE, respectively. Indeed, the inhibition of these metabolic enzymes has been
      considered as a promising factor for pharmacologic intervention in a diversity of
      disturbances.

PMID- 29457668
TI  - The relationships between depression, neuroticism, and attitudes (NDA model) in
      heroin abusers in Taiwan.
AB  - BACKGROUND AND OBJECTIVES: Heroin use is a severe problem worldwide. To develop
      more effective treatments for heroin abusers, a comprehensive psychosocial model
      of heroin use should be established and examined. We created and assessed a
      neuroticism, depression, attitudes, and heroin addiction (NDA) model. METHODS: In
      this cross-sectional study, 234 patients undergoing methadone replacement
      treatment were recruited from psychiatric clinics. We used Structural Equation
      Modeling (SEM) to assess all for neuroticism, depression, and a positive outcome
      expectancy (POE) (attitudes). RESULTS: The full model had acceptable goodness-of
      fit indices, but neuroticism was not significantly associated with a POE or
      heroin use. A reduced model that deleted insignificant paths had better goodness
      of-fit indices, and neuroticism had indirect effects on heroin use via depression
      and a POE CONCLUSIONS: Our findings provide evidence that depression,
      neuroticism, and POE affect heroin use. We also found that POE mediates between
      depression and heroin use. Despite the emotional regulation strategies
      recommended to help heroin abusers with depression to reduce the likelihood of
      their heroin use, teaching them with negative attitudes using heroin should also
      be considered when developing treatments for heroin abusers with depression.
      SCIENTIFIC SIGNIFICANCE: Our findings provide a comprehensive mechanism of
      addiction that is integrated with emotion, cognition, and personality. Drug
      related beliefs and emotional regulation can be targeted to reduce the likelihood
      of relapse in abusers with higher levels of neuroticism. (Am J Addict 2018;27:139
      143).

PMID- 29457670
TI  - Intelligent Albumin-MnO2 Nanoparticles as pH-/H2 O2 -Responsive Dissociable
      Nanocarriers to Modulate Tumor Hypoxia for Effective Combination Therapy.

PMID- 29457669
TI  - N-Acetyl-cysteine mediated inhibition of spermatogonial cells apoptosis against
      malathion exposure in testicular tissue.
AB  - Toxicological studies so far suggest that excessive use of malathion, an
      organophosphate insecticide, causes serious ill-effects in mammalian reproductive
      physiology. The present study aims at assessing malathion-induced toxicity in a
      dose- and time-dependent manner with mitigating effects of N-acetyl-l-cysteine.
      The testicular germ cell viability was monitored using MTT assay, where NAC,
      being an antioxidant significantly reduced malathion-induced toxicity by
      enhancing the frequency of cell viability. The histomorphological analysis showed
      that NAC successfully diminished several apoptotic features in testicular cells,
      induced by malathion. The differential EB/AO staining revealed a significant
      decline in the percentage of apoptosis after NAC supplementation. NAC also
      diminished the malathion-induced DNA fragmentation along with significantly
      reduction in oxidative stress parameters causing decrease in lipid peroxidation
      and enhancement of ferric reducing antioxidant power within testicular germ
      cells. Thus, NAC mitigated the malathion-induced toxicity, proving its potential
      in infertility treatment.

PMID- 29457671
TI  - Abstinence and reduced frequency of use are associated with improvements in
      quality of life among treatment-seekers with cannabis use disorder.
AB  - BACKGROUND AND OBJECTIVE: Many patients with cannabis use disorder (CUD) do not
      achieve or do not have abstinence as a goal of treatment, rather they reduce
      their use. Assessing outcome measures as they relate to functioning and
      reductions in cannabis use is an important area of study. Quality of life (QoL)
      shows promise as one such measure. Past studies have demonstrated gender
      differences in QoL and CUD. We aim to assess (1) the relationship between
      cannabis use and QoL and (2) gender effects in an outpatient medication treatment
      study for CUD. METHODS: Data from an 11-weeks, double-blind, placebo-controlled
      trial of lofexidine and dronabinol for CUD (n = 62) was analyzed. Pearson's
      correlations between baseline QoL as measured with the Quality of Life,
      Enjoyment, and Satisfaction Questionnaire-Short Form (QLES-Q-SF) and cannabis use
      assessed with modified timeline follow-back (TLFB) were examined. Multiple linear
      regression models of cannabis use on end of study QLES-Q-SF were analyzed, while
      adjusting for baseline QLES-Q-SF, study arm, and gender. Moderation effects with
      gender were also tested. RESULTS: No significant association between baseline
      cannabis use and QoL was found. End of study abstinence (F1,47   =  8.34, p =
      .006) and reduced proportion of using days (F1,47  = 9.48, p = .004) were each
      significantly associated with end of study QoL. Reduction in grams (F1,27  =
      0.25, p = .62) was not associated with QoL at end of study. Gender was not a
      significant moderator. DISCUSSION AND CONCLUSIONS: Abstinence and lower frequency
      of use are associated with higher QoL, regardless of gender. SCIENTIFIC
      SIGNIFICANCE: This is the first time QoL has been demonstrated to change over the
      course of CUD medication treatment. QoL is an important outcome in CUD treatment.
      TRIAL REGISTRATION: NCT01020019. (Am J Addict 2018;27:101-107).

PMID- 29457672
TI  - Gambling-related cognitive distortions predict level of function among US
      veterans seeking treatment for gambling disorders.
AB  - BACKGROUND AND OBJECTIVES: Gambling Disorder (GD) is characterized by recurrent
      gambling behavior that is associated with significant impairment and distress,
      high psychiatric comorbidities, and high functional disability. The military
      veteran population appears particularly susceptible to developing the disorder,
      but relatively little has been studied among this population. The purpose of the
      present study is to investigate the clinical psychopathologies and comorbidities
      of veterans seeking treatment for problem gambling and how problem gambling may
      impact functioning. METHODS: Treatment-seeking veterans meeting criteria for GD
      (N = 61) underwent a structured clinical interview and completed the South Oaks
      Gambling Screen (SOGS), the Gambling Symptom Assessment Scale (G-SAS), the Yale
      Brown Obsessive-Compulsive Scale for Gambling Disorder (PG-YBOCS), the Gambling
      Belief Questionnaire (GBQ), the Barratt Impulsiveness Scale (BIS-11), and the
      Sheehan Disability Scale (SDS). RESULTS: Veterans seeking treatment for GD had
      high rates of psychiatric and addiction disorder comorbidities. Few veterans had
      previously sought treatment and most reported substantive challenges in social
      and occupational functioning. When determining how gambling-related
      characteristics (ie, severity and cognitive distortions) impact function,
      severity of cognitive distortions was the strongest statistical predictor of
      overall functional disability. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The
      findings from this study indicate that there is high comorbidity between GD and
      other psychiatric and addictive disorders, as well as social and occupational
      functioning. In addition, cognitive distortions related to gambling relate
      importantly to overall functioning and should be considered in the development of
      interventions for veterans with GD. (Am J Addict 2018;27:108-115).

PMID- 29457673
TI  - Educ'alcool response to Petticrew et al.: 'How alcohol industry organisations
      mislead the public about alcohol and cancer'.

PMID- 29457675
TI  - Oocyte-activating capacity of fresh and frozen-thawed spermatids in the common
      marmoset (Callithrix jacchus).
AB  - The common marmoset (Callithrix jacchus) represents a promising nonhuman primate
      model for the study of human diseases because of its small size, ease of
      handling, and availability of gene-modified animals. Here, we aimed to devise
      reproductive technology for marmoset spermatid injection using immature males for
      a possible rapid generational turnover. Spermatids at each step could be
      identified easily by their morphology under differential interference microscopy:
      thus, early round spermatids had a round nucleus with a few nucleolus-like
      structures and abundant cytoplasm, as in other mammals. The spermatids acquired
      oocyte-activating capacity at the late round spermatid stage, as confirmed by the
      resumption of meiosis and Ca2+ oscillations upon injection into mouse oocytes.
      The spermatids could be cryopreserved efficiently with a simple medium containing
      glycerol and CELL BANKER(r). Late round or elongated spermatids first appeared at
      10-12 months of age, 6-8 months before sexual maturation. Marmoset oocytes
      microinjected with frozen-thawed late round or elongated spermatids retrieved
      from a 12-month-old male marmoset developed to the 8-cell stage without the need
      for artificial oocyte activation stimulation. Thus, it might be possible to
      shorten the intergeneration time by spermatid injection, from 2 years (by natural
      mating) to 13-15 months including gestation.

PMID- 29457674
TI  - A review of brain stimulation methods to treat substance use disorders.
AB  - BACKGROUND: Substance use disorders (SUDs) are a leading cause of disability
      worldwide. While several pharmacological and behavioral treatments for SUDs are
      available, these may not be effective for all patients. Recent studies using non
      invasive neuromodulation techniques including Repetitive Transcranial Magnetic
      Stimulation (rTMS), Transcranial Direct Current Stimulation (tDCS), and Deep
      Brain Stimulation (DBS) have shown promise for SUD treatment. OBJECTIVE: Multiple
      studies were evaluated investigating the therapeutic potential of non-invasive
      brain stimulation techniques in treatment of SUDs. METHOD: Through literature
      searches (eg, PubMed, Google Scholar), 60 studies (2000-2017) were identified
      examining the effect of rTMS, tDCS, or DBS on cravings and consumption of SUDs,
      including tobacco, alcohol, cannabis, opioids, and stimulants. RESULTS: rTMS and
      tDCS demonstrated decreases in drug craving and consumption, while early studies
      with DBS suggest similar results. Results are most encouraging when stimulation
      is targeted to the Dorsolateral Prefrontal Cortex (DLPFC). CONCLUSIONS: Short
      term treatment with rTMS and tDCS may have beneficial effects on drug craving and
      consumption. Future studies should focus on extending therapeutic benefits by
      increasing stimulation frequency and duration of treatment. SCIENTIFIC
      SIGNIFICANCE: The utility of these methods in SUD treatment and prevention are
      unclear, and warrants further study using randomized, controlled designs. (Am J
      Addict 2018;27:71-91).

PMID- 29457676
TI  - Subthalamic nucleus pathology contributes to repetitive behavior expression and
      is reversed by environmental enrichment.
AB  - Repetitive motor behaviors are common in neurodevelopmental, psychiatric and
      neurological disorders. Despite their prevalence in certain clinical populations,
      our understanding of the neurobiological cause of repetitive behavior is lacking.
      Likewise, not knowing the pathophysiology has precluded efforts to find effective
      drug treatments. Our comparisons between mouse strains that differ in their
      expression of repetitive behavior showed an important role of the subthalamic
      nucleus (STN). In mice with high rates of repetitive behavior, we found
      significant differences in dendritic spine density, gene expression and neuronal
      activation in the STN. Taken together, these data show a hypoglutamatergic state.
      Furthermore, by using environmental enrichment to reduce repetitive behavior, we
      found evidence of increased glutamatergic tone in the STN with our measures of
      spine density and gene expression. These results suggest the STN is a major
      contributor to repetitive behavior expression and highlight the potential of
      drugs that increase STN function to reduce repetitive behavior in clinical
      populations.

PMID- 29457678
TI  - Micronutrient dietary patterns associated with type 2 diabetes mellitus among
      women of the E3N-EPIC (Etude Epidemiologique aupres de femmes de l'Education
      Nationale) cohort study.
AB  - BACKGROUND: Micronutrients play a key role in type 2 diabetes mellitus (T2DM),
      but methodological difficulties arise from their collinearity and
      interdependencies with foods. The aim of the present study was to identify
      micronutrient dietary patterns in the E3N-EPIC (Etude Epidemiologique aupres de
      femmes de l'Education Nationale) cohort and to investigate their association with
      risk of T2DM. METHODS: Principal component analysis was used to identify
      micronutrient patterns among 71 270 women from the E3N-EPIC cohort. Associations
      between micronutrient patterns and risk of T2DM were quantified by hazard ratios
      (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards regression
      models, adjusted for potential confounders. RESULTS: Six micronutrient patterns
      were identified explaining 78% of the total variance in micronutrient intake. A
      positive association was found between T2DM and a pattern highly correlated with
      intake of vitamins B2 and B5 (HR 1.34; 95% CI 1.16-1.56). Similarly, a positive
      association was found with a pattern characterized by high intakes of vitamin B12
      and retinol, and a low intake of vitamin C (HR 1.30; 95% CI 1.15-1.48). An
      inverse association was observed between T2DM and another two patterns: one
      correlated with magnesium and vitamin B3 (HR 0.75; 95% CI 0.66-0.86), and the
      other correlated with manganese intake (HR 0.82; 95% CI 0.72-0.94). CONCLUSIONS:
      The findings of the present study identify micronutrients that have an effect on
      the risk of T2DM, and enable better understanding of the complexity of the diet
      when investigating the association between micronutrients and T2DM.

PMID- 29457679
TI  - Features of Protonation of the Simplest Weakly Basic Molecules, SO2 , CO, N2 O,
      CO2 , and Others by Solid Carborane Superacids.
AB  - An experimental study on protonation of simple weakly basic molecules (L) by the
      strongest solid superacid, H(CHB11 F11 ), showed that basicity of SO2 is high
      enough (during attachment to the acidic H atoms at partial pressure of 1 atm) to
      break the bridged H-bonds of the polymeric acid and to form a mixture of solid
      mono- LH+ ???An- , and disolvates, L-H+ -L. With a decrease in the basicity of
      L=CO (via C), N2 O, and CO (via O), only proton monosolvates are formed, which
      approach L-H+ -An- species with convergence of the strengths of bridged H-bonds.
      The molecules with the weakest basicity, such as CO2 and weaker, when attached to
      the proton, cannot break the bridged H-bond of the polymeric superacid, and the
      interaction stops at stage of physical adsorption. It is shown here that under
      the conditions of acid monomerization, it is possible to protonate such weak
      bases as CO2 , N2 , and Xe.

PMID- 29457677
TI  - The contribution of a negative colorectal screening test result to symptom
      appraisal and help-seeking behaviour among patients subsequently diagnosed with
      an interval colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) screening programmes using a guaiac faecal
      occult blood test (gFOBt) reduce CRC mortality. Interval cancers are diagnosed
      between screening rounds: reassurance from a negative gFOBt has the potential to
      influence the pathway to diagnosis of an interval colorectal cancer. METHODS:
      Twenty-six semi-structured face-to-face interviews were carried out in Scotland
      and England, with individuals diagnosed with an interval colorectal cancer
      following a negative gFOBt result. RESULTS: Participants reported they were
      reassured by a negative gFOBt, interpreting their result as an "all clear".
      Therefore, most did not suspect cancer as a possible cause of symptoms and many
      did not recall their screening result during symptom appraisal. Among those who
      did consider cancer, and did think about their screening test result, reassurance
      from a negative gFOBt led some to "downplay" the seriousness of their symptoms
      with some interviewees explicitly stating that their negative test result
      contributed to a delayed decision to seek help. CONCLUSION: Screening
      participants need to be informed of the limitations of screening and the ongoing
      risk of developing colorectal cancer even when in receipt of a negative result:
      the importance of minimizing delay in seeking medical advice for colorectal
      symptoms should be emphasized.

PMID- 29457680
TI  - Chronic lead exposure enhances the sympathoexcitatory response associated with
      P2X4 receptor in rat stellate ganglia.
AB  - Chronic lead exposure causes peripheral sympathetic nerve stimulation, including
      increased blood pressure and heart rate. Purinergic receptors are involved in the
      sympathoexcitatory response induced by myocardial ischemia injury. However,
      whether P2X4 receptor participates in sympathoexcitatory response induced by
      chronic lead exposure and the possible mechanisms are still unknown. The aim of
      this study was to explore the change of the sympathoexcitatory response induced
      by chronic lead exposure via the P2X4 receptor in the stellate ganglion (SG).
      Rats were given lead acetate through drinking water freely at doses of 0 g/L
      (control group), 0.5 g/L (low lead group), and 2 g/L (high lead group) for 1
      year. Our results demonstrated that lead exposure caused autonomic nervous
      dysfunction, including blood pressure and heart rate increased and heart rate
      variability (HRV) decreased. Western blotting results indicated that after lead
      exposure, the protein expression levels in the SG of P2X4 receptor, IL-1beta and
      Cx43 were up-regulated, the phosphorylation of p38 mitogen-activated protein
      kinase (MAPK) was activated. Real-time PCR results showed that the mRNA
      expression of P2X4 receptor in the SG was higher in lead exposure group than that
      in the control group. Double-labeled immunofluorescence results showed that P2X4
      receptor was co-expressed with glutamine synthetase (GS), the marker of satellite
      glial cells (SGCs). These changes were positively correlated with the dose of
      lead exposure. The up-regulated expression of P2X4 receptor in SGCs of the SG
      maybe enhance the sympathoexcitatory response induced by chronic lead exposure.

PMID- 29457681
TI  - Analysis of RPA190 revealed multiple positively selected mutations associated
      with metalaxyl resistance in Phytophthora infestans.
AB  - BACKGROUND: Metalaxyl is a phenylamide fungicide, introduced for oomycete
      management in the 1970s. RPA190 gene has been reported to be associated with
      metalaxyl resistance, although other genes may also be involved in the process.
      This study assessed the evolutionary association of amino acid (AA) mutations in
      RPA190 with metalaxyl resistance in Phytophthora infestans. RESULTS: All isolates
      from Yunnan were resistant to metalaxyl with multiple AA mutations in RPA190. Two
      main evolutionary pathways were found in metalaxyl resistance: in one pathway,
      RPA190 from sensitive isolates (SAA) underwent a single type AA mutation at
      position 1476, changing from valine to glycine (V1476G); the second pathway
      involved multiple steps of point mutations. In a phylogenetic tree, nucleotide
      sequences of the gene clustered into six clades largely corresponding to AA
      isoform groups. Among the clusters, sequences carrying mutations V1476G and P980S
      formed two independent clades; other clades shared a common mutation of F382Y.
      All three mutations together with another two were shown to be under positive
      selection and the number of AA mutations in an isolate was positively correlated
      with EC50 values. CONCLUSION: Multiple mutations such as V1476G, P980S, and F382Y
      in RPA190 contribute to metalaxyl resistance, and resistance to metalaxyl can
      emerge in at least two independent pathways in P. infestans. (c) 2018 Society of
      Chemical Industry.

PMID- 29457682
TI  - Predictive Models in Ecotoxicology: Bridging the Gap Between Scientific Progress
      and Regulatory Applicability.
AB  - This special series is the outcome of the session "Predictive models in
      ecotoxicology: Bridging the gap between scientific progress and regulatory
      applicability," held at the 27th SETAC Europe annual meeting (Brussels, May
      2017). In this foreword the rationale behind the special series, the reasons for
      proposing it, and its objectives are described briefly. Integr Environ Assess
      Manag 2018;14:601-603. (c) 2018 SETAC.

PMID- 29457684
TI  - Poorly differentiated neuroendocrine carcinoma of the breast with Merkel cell
      features.
AB  - Neuroendocrine carcinoma of the breast is a rare tumor subtype comprising less
      than 1% of breast cancers in the United States. Merkel cell features within this
      rare subtype are even rarer. We report a neuroendocrine breast carcinoma with
      Merkel cell features. The patient underwent breast conservation therapy and a
      sentinel lymph node biopsy. Unfortunately, the tumor was extremely aggressive and
      at 5 weeks postoperatively she presented with widely metastatic disease. Due to
      the aggressive nature of this tumor, we reviewed the literature and treatment
      options for this rare variant of a rare subtype.

PMID- 29457683
TI  - The Dewar Isomer of 1,2-Dihydro-1,2-azaborinines: Isolation, Fragmentation, and
      Energy Storage.
AB  - The photochemistry of 1,2-dihydro-1,2-azaborinine derivatives was studied under
      matrix isolation conditions and in solution. Photoisomerization occurs
      exclusively to the Dewar valence isomers upon irradiation with UV light (>280 nm)
      with high quantum yield (46 %). Further photolysis with UV light (254 nm) results
      in the formation of cyclobutadiene and an iminoborane derivative. The thermal
      electrocyclic ring-opening reaction of the Dewar valence isomer back to the 1,2
      dihydro-1-tert-butyldimethylsilyl-2-mesityl-1,2-azaborinine has an activation
      barrier of (27.0+/-1.2) kcal mol-1 . In the presence of the Wilkinson catalyst,
      the ring opening occurs rapidly and exothermically (DeltaH=(-48+/-1) kcal mol-1 )
      at room temperature.

PMID- 29457685
TI  - Tailored Microstructured Hyperpolarizing Matrices for Optimal Magnetic Resonance
      Imaging.
AB  - Tailoring the physical features and the porous network architecture of silica
      based hyperpolarizing solids containing TEMPO radicals, known as HYPSO (hybrid
      polarizing solids), enabled unprecedented performance of dissolution dynamic
      nuclear polarization (d-DNP). High polarization values up to P(1 H)=99 % were
      reached for samples impregnated with a mixture of H2 O/D2 O and loaded in a 6.7 T
      polarizer at temperatures around 1.2 K. These HYPSO materials combine the best
      performance of homogeneous DNP formulations with the advantages of solid
      polarizing matrices, which provide hyperpolarized solutions free of any
      potentially toxic-additives (radicals and glass-forming agents). The
      hyperpolarized solutions can be expelled from the porous solids, filtered, and
      rapidly transferred either to a nuclear magnetic resonance (NMR) spectrometer or
      to a magnetic resonance imaging (MRI) system.

PMID- 29457686
TI  - Viable but non-culturable and persistence describe the same bacterial stress
      state.
AB  - Bacteria are often thought of as having two dormant phenotypes: the viable but
      non-culturable (VBNC) state and the persister state. Here we investigate the
      relatedness of the two stress-induced phenotypes at the single-cell level and
      examine cell morphology and quantify cell resuscitation. Using the classic
      starvation conditions to create VBNC cells, we found that the majority of the
      remaining Escherichia coli population are spherical, have empty cytosol and fail
      to resuscitate; however, some of the spherical cells resuscitate immediately
      (most probably those with dense cytosol). Critically, all the culturable cells in
      this starved population became persister cells within 14 days of starvation. We
      found that the persister cells initially are rod-like, have clear but limited
      membrane damage, can resuscitate immediately and gradually become spherical by
      aging. After 24 h, only rod-shaped persister cells survive, and all the spherical
      cells lyse. Both cell populations formed under the VBNC-inducing conditions and
      the persister conditions are metabolically inactive. Therefore, the bacterial
      population consists of dead cells and persister cells in the VBNC-inducing
      conditions; that is, the non-lysed particles that do not resuscitate are dead,
      and the dormant cells that resuscitate are persister cells. Hence, 'VBNC' and
      'persister' describe the same dormant phenotype.

PMID- 29457687
TI  - Substrate Binding Drives Active-Site Closing of Human Blood Group B
      Galactosyltransferase as Revealed by Hot-Spot Labeling and NMR Spectroscopy
      Experiments.
AB  - Crystallography has shown that human blood group A (GTA) and B (GTB)
      glycosyltransferases undergo transitions between "open", "semiclosed", and
      "closed" conformations upon substrate binding. However, the timescales of the
      corresponding conformational reorientations are unknown. Crystal structures show
      that the Trp and Met residues are located at "conformational hot spots" of the
      enzymes. Therefore, we utilized 15 N side-chain labeling of Trp residues and 13 C
      methyl labeling of Met residues to study substrate-induced conformational
      transitions of GTB. Chemical-shift perturbations (CSPs) of Met and Trp residues
      in direct contact with substrate ligands reflect binding kinetics, whereas the
      CSPs of Met and Trp residues at remote sites reflect conformational changes of
      the enzyme upon substrate binding. Acceptor binding is fast on the chemical-shift
      timescale with rather small CSPs in the range of less than approximately 20 Hz.
      Donor binding matches the intermediate exchange regime to yield an estimate for
      exchange rate constants of approximately 200-300 Hz. Donor or acceptor binding to
      GTB saturated with acceptor or donor substrate, respectively, is slow (<10 Hz),
      as are coupled protein motions, reflecting mutual allosteric control of donor and
      acceptor binding. Remote CSPs suggest that substrate binding drives the enzyme
      into the closed state required for catalysis. These findings should contribute to
      better understanding of the mechanism of glycosyl transfer of GTA and GTB.

PMID- 29457689
TI  - Halloysite nanotubes-induced Al accumulation and oxidative damage in liver of
      mice after 30-day repeated oral administration.
AB  - Halloysite (Al2 Si2 O5 (OH)4 .nH2 O) nanotubes (HNTs) are natural clay materials
      and widely applied in many fields due to their natural hollow tubular structures.
      Many in vitro studies indicate that HNTs exhibit a high level of
      biocompatibility, however the in vivo toxicity of HNTs remains unclear. The
      objective of this study was to assess the hepatic toxicity of the purified HNTs
      in mice via oral route. The purified HNTs were orally administered to mice at 5,
      50, and 300 mg/kg body weight (BW) every day for 30 days. Oral administration of
      HNTs stimulated the growth of the mice at the low dose (5 mg/kg BW) with no liver
      toxicity, but inhibited the growth of the mice at the middle (50 mg/kg BW) and
      high (300 mg/kg BW) doses. In addition, oral administration of HNTs at the high
      dose caused Al accumulation in the liver but had no marked effect on the Si
      content in the organ. The Al accumulation caused significant oxidative stress in
      the liver, which induced hepatic dysfunction and histopathologic changes. These
      findings demonstrated that Al accumulation-induced oxidative stress played an
      important role in the oral HNTs-caused liver injury.

PMID- 29457688
TI  - A network of regulators promotes dehydration tolerance in Escherichia coli.
AB  - The ability to survive conditions of low water activity is critical for the
      survival of many bacteria in the environment and facilitates disease transmission
      through food and contaminated surfaces. However, the molecular mechanisms that
      enable bacteria to withstand this condition remain poorly understood. Here we
      describe a network of regulators in Escherichia coli that are important for this
      bacterium to survive dehydration. We found that the transcriptional regulator
      DksA and the general stress response regulator RpoS play a critical role. From a
      plasmid genomic library screen, we identified two additional regulators, Crl and
      ArcZ, that promote dehydration tolerance through modulation of RpoS. We also
      found that LexA, RecA and ArcA contribute to survival. Our results identify key
      regulators that enable E. coli to tolerate dehydration and suggest a hierarchical
      network is involved in protection against cellular damage associated with this
      stress.

PMID- 29457690
TI  - Carbon Atom Hybridization Matters: Ultrafast Humidity Response of Graphdiyne
      Oxides.
AB  - Graphdiyne oxide (GDO), the oxidized form of graphdiyne (GDY), exhibits an
      ultrafast humidity response with an unprecedented response speed (ca. 7 ms),
      which is three times faster than that of graphene oxide (GO) with the same
      thickness and O/C ratio. The ultrafast humidity response of GDO is considered to
      benefit from the unique carbon hybridization of GDO, which contains acetylenic
      bonds that are more electron-withdrawing than ethylenic bonds in GO, consequently
      giving rise to a faster binding rate with water. This distinctive structure-based
      property enables the fabrication of a novel GDO-based humidity sensor with an
      ultrafast response speed and good selectivity against other kinds of gas
      molecules as well as high sensitivity. These properties allow the sensor to
      accurately monitor the respiration rate change of human and hypoxic rats.

PMID- 29457691
TI  - Apportioning bacterial carbon source utilization in soil using 14 C isotope
      analysis of FISH-targeted bacterial populations sorted by fluorescence activated
      cell sorting (FACS): 14 C-FISH-FACS.
AB  - An unresolved need in microbial ecology is methodology to enable quantitative
      analysis of in situ microbial substrate carbon use at the population level. Here,
      we evaluated if a novel combination of radiocarbon-labelled substrate tracing,
      fluorescence in situ hybridisation (FISH) and fluorescence-activated cell sorting
      (FACS) to sort the FISH-targeted population for quantification of incorporated
      radioactivity (14 C-FISH-FACS) can address this need. Our test scenario used FISH
      probe PSE1284 targeting Pseudomonas spp. (and some Burkholderia spp.) and
      salicylic acid added to rhizosphere soil. We examined salicylic acid-14 C fate
      (mineralized, cell-incorporated, extractable and non-extractable) and mass
      balance (0-24 h) and show that the PSE1284 population captured ~ 50% of the
      Nycodenz extracted biomass 14 C. Analysis of the taxonomic distribution of the
      salicylic acid biodegradation trait suggested that PSE1284 population success was
      not due to conservation of this trait but due to competitiveness for the added
      carbon. Adding 50KBq of 14 C sample-1 enabled detection of 14 C in the sorted
      population at ~ 60-600 times background; a sensitivity which demonstrates
      potential extension to analysis of rarer/less active populations. Given its
      sensitivity and compatibility with obtaining a C mass balance, 14 C-FISH-FACS
      allows quantitative dissection of C flow within the microbial biomass that has
      hitherto not been achieved.

PMID- 29457692
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 9/2018.

PMID- 29457693
TI  - Growth yield and selection of nosZ clade II types in a continuous enrichment
      culture of N2 O respiring bacteria.
AB  - Nitrous oxide (N2 O) reducing microorganisms may be key in the mitigation of N2 O
      emissions from managed ecosystems. However, there is still no clear understanding
      of the physiological and bioenergetic implications of microorganisms possessing
      either of the two N2 O reductase genes (nosZ), clade I and the more recently
      described clade II type nosZ. It has been suggested that organisms with nosZ
      clade II have higher growth yields and a lower affinity constant (Ks ) for N2 O.
      We compared N2 O reducing communities with different nosZI/nosZII ratios selected
      in chemostat enrichment cultures, inoculated with activated sludge, fed with N2 O
      as a sole electron acceptor and growth limiting factor and acetate as electron
      donor. From the sequencing of the 16S rRNA gene, FISH and quantitative PCR of
      nosZ and nir genes, we concluded that betaproteobacterial denitrifying organisms
      dominated the enrichments with members within the family Rhodocyclaceae being
      highly abundant. When comparing cultures with different nosZI/nosZII ratios, we
      did not find support for (i) a more energy conserving N2 O respiration pathway in
      nosZ clade II systems, as reflected in the growth yield per mole of substrate, or
      (ii) a higher affinity for N2 O, defined by MUmax /Ks , in organisms with nosZ
      clade II.

PMID- 29457694
TI  - Exploring effects of self-management on glycemic control using a modified
      information-motivation-behavioral skills model in type 2 diabetes mellitus
      patients in Shanghai, China: A cross-sectional study.
AB  - BACKGROUND: The original information-motivation-behavioral skills (IMB) model has
      been verified in type 2 diabetes mellitus (T2DM) patients, but the effects of the
      model on glycemic control remain unclear. The aim of this study was to modify the
      IMB model to explore the effects of self-management on glycemic control in T2DM
      patients in Shanghai, China. METHODS: A cross-sectional study was conducted on
      participants recruited using a convenience sampling method between June and
      August 2015 in three tertiary hospitals and four community health service
      centers; 796 participants meeting the inclusion criteria (age >=18 years and a
      diagnosis of T2DM) completed a questionnaire and blood test for glycemic control.
      Structural equation models were used to test the IMB framework. RESULTS: The
      modified model demonstrated an acceptable fit of the data. Paths from information
      to self-management behaviors (beta = 0.119, P = 0.001) and HbA1c (beta = -0.140,
      P < 0.001), from motivation to behavioral skills (beta = 0.670, P < 0.001), from
      behavioral skills to self-management behaviors (beta = 0.562, P < 0.001), and
      from self-management behaviors to HbA1c (beta = -0.343, P < 0.001) were all
      significant and in the predicted direction. Information and motivation varied
      with each other (r = 0.350, P < 0.001). CONCLUSIONS: Glycemic control can be
      incorporated into the IMB model. The utility of the modified model in the study
      population is validated. Type 2 diabetes mellitus patients with poor control of
      glucose levels may be a better target population for application of the modified
      IMB model.

PMID- 29457695
TI  - Functionalization of a nanostructured hydroxyapatite with Cu(II) compounds as a
      pesticide: in situ transmission electron microscopy and environmental scanning
      electron microscopy observations of treated Vitis vinifera L. leaves.
AB  - BACKGROUND: The present study evaluated a biocompatible material for plant
      protection with the aim of reducing the amount of active substance applied. We
      used a synthetic hydroxyapatite (HA) that has been studied extensively as a
      consequence of its bioactivity and biocompatibility. An aggregation between HA
      nanoparticles and four Cu(II) compounds applied to Vitis vinifera L. leaves as a
      pesticide was studied. Formulations were characterized by X-ray diffraction
      (XRD), dynamic light scattering (DLS) and electron microscopy and applied in
      planta to verify particle aggregation and efficiency in controlling the pathogen
      Plasmopara viticola. RESULTS: The XRD patterns showed different crystalline
      phases dependig on the Cu(II) compound formulated with HA particles, DLS showed
      that nanostructured particles are stable as aggregates out of the nanometer range
      and, in all formulations, transmission electron microscopy (TEM) and
      environmental scanning electron microscopy (ESEM) microscopy showed large
      aggregates which were partially nanostructured and were recognized as stable in
      their micrometric dimensions. Such particles did not show phytotoxic effects
      after their application in planta. CONCLUSION: A formulation based on HA and a
      soluble Cu(II) compound showed promising results in the control of the fungal
      pathogen, confirming the potential role of HA as an innovative delivery system of
      Cu(II) ions. The present work indicates the possibility of improving the
      biological activity of a bioactive substance by modifying its structure through
      an achievable formulation with a biocompatible material. (c) 2018 Society of
      Chemical Industry.

PMID- 29457696
TI  - Reshaping a multimode laser beam into a constructed Gaussian beam for generating
      a thin light sheet.
AB  - Based on the modal analysis method, we developed a model that describes the
      output beam of a diode-pumped solid state (DPSS) laser emitting a multimode beam.
      Measuring the output beam profile in the near field and at the constructed far
      field the individual modes, their respective contributions, and their optical
      parameters are determined. Using this information, the beam is optically reshaped
      into a quasi-Gaussian beam by the interference and superposition of the various
      modes. This process is controlled by a mode modulator unit that includes
      different meso-aspheric elements and a soft-aperture. The converted beam is
      guided into a second optical unit comprising achromatic-aspheric elements to
      produce a thin light sheet for ultramicroscopy. We found that this light sheet is
      markedly thinner and exhibits less side shoulders compared with a light sheet
      directly generated from the output of a DPSS multimode laser.

PMID- 29457698
TI  - Feasibility of a novel tacking method of securing mesh in transabdominal
      preperitoneal inguinal hernia repair: Secure tacking against recurrence.
AB  - INTRODUCTION: Postoperative chronic pain is an important outcome of hernia
      surgery. In laparoscopic hernia surgery, either fixation outside the trapezoid of
      disaster or no fixation is recommended to avoid postoperative pain. To avoid
      recurrence are transabdominal preperitoneal (TAPP) hernia repair, the
      myopectineal orifice must be covered with mesh during TAPP, but lifting or
      shrinking of the mesh can lead to recurrence. The aim of this study was to
      evaluate the feasibility of a novel technique for mesh fixation to prevent the
      mesh from lifting off. METHODS: After the preperitoneal space was created during
      TAPP, the anatomy of the lateral cutaneous nerve of the thigh or the femoral
      branch of the genitofemoral nerve within the trapezoid of disaster was checked.
      The mesh was tacked at the trapezoid of disaster without nerve injury, and the
      mesh was fixed with circumferential tacking. We call this procedure secure
      tacking against recurrence (STAR). We treated 391 adult patients (478 hernias)
      with TAPP repair; novel tacking was used in some patients (STAR group, 236
      hernias). The results of the STAR group were retrospectively compared with those
      of patients in whom we did not use this novel tacking (conventional group, 242
      hernias). RESULTS: There was no postoperative chronic pain in either group. There
      were no cases of hernia recurrence in the STAR group, but there were four cases
      of hernia recurrence in the conventional group (0% vs 1.7%, P = 0.047). These
      four recurrences consisted of indirect hernia and mesh lifting on the lateral
      side. CONCLUSION: The STAR procedure is feasible and safety as a standard
      procedure for securing the mesh during TAPP.

PMID- 29457699
TI  - Personality: Distraction or driver in the diagnosis of depression.

PMID- 29457700
TI  - Impact of home spirometry on medication adherence among adolescents with cystic
      fibrosis.
AB  - OBJECTIVE: Medication adherence among adolescents with cystic fibrosis (CF) is
      often suboptimal and this has significant impact on their health and quality of
      life. The purpose of the study was to evaluate the impact of frequent home
      pulmonary function (PFT) monitoring on medication adherence among adolescents
      with CF. HYPOTHESIS: We hypothesized that weekly home PFT monitoring will improve
      adherence while not significantly adding to the treatment burden. METHODS:
      Individuals aged 12-21 years with CF were provided a spirometer to measure PFTs
      weekly for 1 year. Results were reviewed weekly via telephone. PFT data were
      downloaded from the device during quarterly clinic visits. Adherence was
      calculated from prescription refill data and compared to the previous year.
      Perceptions of treatment burden were assessed using the CF questionnaire-revised
      (CFQ-R) quality of life measure. Health outcome measures including nutritional
      status and PFTs from clinic were collected for the study period and the year
      prior. RESULTS: Thirty-nine subjects participated in the study. Mean age was
      15.89 +/- 2.18 years and 54% were female. Mean adherence to weekly spirometry
      monitoring was 59.47 +/- 24.60%. Values generated on the device showed good
      correlation with those obtained in clinic. Mean medication possession ratio (MPR)
      was 60% in the previous year and 65% during the study (P = 0.04). Mean treatment
      burden scaled score on the CFQ-R was 68 at enrollment and 66 at study completion
      (P = 0.14). CONCLUSIONS: Frequent home PFT monitoring is feasible in CF
      adolescents and could successfully improve medication adherence without
      significantly impacting treatment burden.

PMID- 29457701
TI  - Identification of the novel HLA-B*18:37:02 allele in a Croatian individual.
AB  - The new allele HLA-B*18:37:02 differs from HLA-B*18:37:01 by one nucleotide
      substitutions in exon 2.

PMID- 29457702
TI  - Short time window for transmissibility of African swine fever virus from a
      contaminated environment.
AB  - Since the introduction of African swine fever virus (ASFV) into the Baltic states
      and Poland in 2014, the disease has continued to spread within these regions. In
      2017, the virus spread further west and the first cases of disease were reported
      in the Czech Republic and Romania, in wild boar and domestic pigs, respectively.
      To control further spread, knowledge of different modes of transmission,
      including indirect transmission via a contaminated environment, is crucial. Up
      until now, such an indirect mode of transmission has not been demonstrated. In
      this study, transmission via an environment contaminated with excretions from
      ASFV-infected pigs was investigated. Following euthanasia of pigs that were
      infected with an isolate of ASFV from Poland (POL/2015/Podlaskie/Lindholm),
      healthy pigs were introduced into the pens, in which the ASFV-infected pigs had
      been housed. Introduction was performed at 1, 3, 5 or 7 days, following
      euthanasia of the infected pig groups. Pigs, that were introduced into the
      contaminated environment after 1 day, developed clinical disease within 1 week,
      and both ASFV DNA and infectious virus were isolated from their blood. However,
      pigs introduced into the contaminated pens after 3, 5 or 7 days did not develop
      any signs of ASFV infection and no viral DNA was detected in blood samples
      obtained from these pigs within the following 3 weeks. Thus, it was shown that
      exposure of pigs to an environment contaminated with ASFV can result in
      infection. However, the time window for transmissibility of ASFV seems very
      limited, and, within our experimental system, there appears to be a rapid
      decrease in the infectivity of ASFV in the environment.

PMID- 29457703
TI  - Exploration of assistive technology for uniform laparoscopic surgery.
AB  - INTRODUCTION: Laparoscopic surgery is less invasive than open surgery and is now
      common in various medical fields. However, laparoscopic surgery is more difficult
      than open surgery and often requires additional time for the operator to achieve
      mastery. Therefore, we investigated the use of assistive technology for uniform
      laparoscopic surgery. METHODS: We used the OpenCV2 library for augmented reality
      with an ArUco marker to detect and estimate forceps positioning. We used Sense
      HAT as the gyro sensor. The development platforms used were Mac OS X 10.11.3 and
      Raspberry Pi 3, model B. RESULTS: By attaching the ArUco marker to the needle
      holder, we could draw a line vertically to the marker. When the needle was held,
      a cube could be imagined, and both the needle and lines could be used to
      determine the appropriate position. By attaching the gyro sensor to the camera,
      we could detect its angle of rotation. We obtained stabilized images by rotating
      the image by the detected degrees; this was possible for any camera position.
      CONCLUSIONS: Assistive technology allowed us to obtain consecutive converted
      images in real time and may be readily applicable to clinical practice.

PMID- 29457704
TI  - Comparability and repeatability of three commonly used methods for measuring
      endurance capacity.
AB  - Measures of endurance (time to exhaustion) have been used to address a wide range
      of questions in ecomorphological and physiological research, as well as being
      used as a proxy for survival and fitness. Swimming, stationary (circular) track
      running, and treadmill running are all commonly used methods for measuring
      endurance. Despite the use of these methods across a broad range of taxa, how
      comparable these methods are to one another, and whether they are biologically
      relevant, is rarely examined. We used Australian water dragons (Intellagama
      lesueurii), a species that is morphologically adept at climbing, swimming, and
      running, to compare these three methods of endurance and examined if there is
      repeatability within and between trial methods. We found that time to exhaustion
      was not highly repeatable within a method, suggesting that single measures or a
      mean time to exhaustion across trials are not appropriate. Furthermore, we
      compared mean maximal endurance times among the three methods, and found that the
      two running methods (i.e., stationary track and treadmill) were similar, but
      swimming was distinctly different, resulting in lower mean maximal endurance
      times. Finally, an individual's endurance rank was not repeatable across methods,
      suggesting that the three endurance trial methods are not providing similar
      information about an individual's performance capacity. Overall, these results
      highlight the need to carefully match a measure of performance capacity with the
      study species and the research questions being asked so that the methods being
      used are behaviorally, ecologically, and physiologically relevant.

PMID- 29457706
TI  - Reverse Translational Pharmacology Research Is Driven by Big Data.

PMID- 29457707
TI  - Peripheral neurostimulation breaks the shuffling steps patterns in Parkinsonian
      gait: a double blind randomized longitudinal study with Automated Mechanical
      Peripheral Stimulation.
AB  - BACKGROUND: The shuffling steps pattern is a typical feature of gait in patients
      affected by Parkinson's Disease (PD), which progressively reduces their quality
      of life, being related to the risk of falls in this population. Recently,
      Automated Mechanical Peripheral Stimulation (AMPS) was presented as an
      integrative rehabilitative treatment based on peripheral stimulation able to
      improve the gait spatiotemporal parameters in PD patients. AIM: To evaluate the
      effects of AMPS on shuffling steps pattern by analyzing the kinematic and spatio
      temporal gait parameters. DESIGN: Double blind randomized longitudinal study.
      SETTING: Outpatients. POPULATION: PD patients. METHODS: In this double blind
      randomized longitudinal study, 14 patients with PD were treated with effective
      AMPS (AMPS Group), while 14 PD patients were treated with placebo-AMPS (SHAM
      Group); 32 healthy subjects were deemed the control group (CG). A dedicated
      medical device (GondolaTM Medical Technologies, Switzerland) was used to deliver
      both stimulations. Each treatment session lasted about 15 minutes, including
      preparation (approx. 10 to 13 minutes) and stimulation (approx. 2 minutes). All
      PD patients were given six AMPS/SHAM treatments sessions, twice a week, delivered
      during the off-levodopa phase, having withdrawn from dopaminergic medication
      overnight. We evaluated spatio-temporal and kinematic variables of gait with
      quantitative 3D-Gait Analysis as follows: before and after the first intervention
      (acute phase), then after the sixth session (long term phase). RESULTS: We
      detected differences in all gait variables immediately after the first session of
      AMPS treatment and again after the sixth stimulation session. CONCLUSIONS: AMPS
      treatment changes the shuffling steps pattern that is typical of PD subjects,
      increasing the ROM of hip, knee and ankle joints during the gait cycle. CLINICAL
      REHABILITATION IMPACT: This data present further evidence that a rehabilitative
      approach based on the AMPS treatment can induce improvements in the gait pattern
      of patients affected by PD.

PMID- 29457705
TI  - Regulation of specialised metabolites in Actinobacteria - expanding the
      paradigms.
AB  - The increase in availability of actinobacterial whole genome sequences has
      revealed huge numbers of specialised metabolite biosynthetic gene clusters,
      encoding a range of bioactive molecules such as antibiotics, antifungals,
      immunosuppressives and anticancer agents. Yet the majority of these clusters are
      not expressed under standard laboratory conditions in rich media. Emerging data
      from studies of specialised metabolite biosynthesis suggest that the diversity of
      regulatory mechanisms is greater than previously thought and these act at
      multiple levels, through a range of signals such as nutrient limitation,
      intercellular signalling and competition with other organisms. Understanding the
      regulation and environmental cues that lead to the production of these compounds
      allows us to identify the role that these compounds play in their natural habitat
      as well as provide tools to exploit this untapped source of specialised
      metabolites for therapeutic uses. Here, we provide an overview of novel
      regulatory mechanisms that act in physiological, global and cluster-specific
      regulatory manners on biosynthetic pathways in Actinobacteria and consider these
      alongside their ecological and evolutionary implications.

PMID- 29457708
TI  - Stress-Enhanced Interlayer Exchange Coupling and Optical-Mode FMR Frequency in
      Self-Bias FeCoB/Ru/FeCoB Trilayers.
AB  - Nowadays, the most popular method to increase ferromagnetic resonance (FMR)
      frequency ( fr) in self-bias soft magnetic films is to improve the anisotropy
      field HK. However, to push fr to higher frequencies only via raising HK becomes
      increasingly challenging because fr is already higher than 10 GHz by now. In this
      study, we fabricated a series of magnetically anisotropic FeCoB/Ru/FeCoB sandwich
      films possessing antiferromagnetic-like coupling and gradually increased uniaxial
      stress in the FeCoB sublayers from 52 to 110 MPa. It is quite remarkable that the
      acoustic mode of FMR gradually disappears, whereas the optical mode is enhanced
      in these structures. We observed simultaneous enhancement of HK and interlayer
      coupling field ( JIEC) with the uniaxial stress, which leads to a very pronounced
      optical-mode frequency increase from 8.67 to 11.62 GHz with a very sensitive
      stress response of 51 Hz/Pa. In contrast, the fr in a FeCoB single layer
      (acoustic mode) only varies from 3.47 to 5.05 GHz under similar stress. We
      believe that the strain-induced electron density variation of the Ru spacer's
      Fermi surface in the out-of-plane direction is responsible for the enhancement of
      JIEC. This study demonstrates that the antiferromagnetic coupling is a new route
      to achieve higher fr and provides the possibility of engineering and manipulating
      optical-mode resonance simply by controlling the interlayer coupling strength via
      stress.

PMID- 29457709
TI  - Hybrid Donor-Acceptor Polymer Particles with Amplified Energy Transfer for
      Detection and On-Demand Treatment of Breast Cancer.
AB  - Judicious combination of semiconducting polymers with alternating electron donor
      (D) and acceptor (A) segments created hybrid nanoparticles with amplified energy
      transfer and red-shifted emission, while simultaneously providing photothermal
      capabilities. Hybrid D-A polymer particles (H-DAPPs) passively localized within
      orthotopic breast tumors, serving as bright fluorescent beacons. Laser
      stimulation induced heat generation on par with gold nanorods, resulting in
      selective destruction of the tumor. H-DAPPs can also undergo multiple thermal
      treatments, with no loss of fluorescence intensity or photothermal potential.
      These results indicate that H-DAPPs provide new avenues for the synthesis of
      hybrid nanoparticles useful in localized detection and treatment of disease.

PMID- 29457710
TI  - Investigation of alpha-MnO2 Tunneled Structures as Model Cation Hosts for Energy
      Storage.
AB  - Future advances in energy storage systems rely on identification of appropriate
      target materials and deliberate synthesis of the target materials with control of
      their physiochemical properties in order to disentangle the contributions of
      distinct properties to the functional electrochemistry. This goal demands
      systematic inquiry using model materials that provide the opportunity for
      significant synthetic versatility and control. Ideally, a material family that
      enables direct manipulation of characteristics including composition, defects,
      and crystallite size while remaining within the defined structural framework
      would be necessary. Accomplishing this through direct synthetic methods is
      desirable to minimize the complicating effects of secondary processing. The
      structural motif most frequently used for insertion type electrodes is based on
      layered type structures where ion diffusion in two dimensions can be envisioned.
      However, lattice expansion and contraction associated with the ion movement and
      electron transfer as a result of repeated charge and discharge cycling can result
      in structural degradation and amorphization with accompanying loss of capacity.
      In contrast, tunnel type structures embody a more rigid framework where the
      inherent structural design can accommodate the presence of cations and often
      multiple cations. Of specific interest are manganese oxides as they can exhibit a
      tunneled structure, termed alpha-MnO2, and are an important class of nanomaterial
      in the fields of catalysis, adsorption-separation, and ion-exchange. The alpha
      MnO2 structure has one-dimensional 2 * 2 tunnels formed by corner and edge
      sharing manganese octahedral [MnO6] units and can be readily substituted in the
      central tunnel by a variety of cations of varying size. Importantly, alpha-MnO2
      materials possess a rich chemistry with significant synthetic versatility
      allowing deliberate synthetic control of structure, composition, crystallite
      size, and defect content. This Account considers the investigation of alpha-MnO2
      tunnel type structures and their electrochemistry. Examination of the reported
      findings on this material family demonstrates that multiple physiochemical
      properties influence the electrochemistry. The retention of the parent structure
      during charge and discharge cycling, the material composition including the
      identity and content of the central cation, the surface condition including
      oxygen vacancies, and crystallite size have all been demonstrated to impact
      electrochemical function. The selection of the alpha-MnO2 family of materials as
      a model system and the ability to control the variables associated with the
      structural family affirm that full investigation of the mechanisms related to
      active materials in an electrochemical system demands concerted efforts in
      synthetic material property control and multimodal characterization, combined
      with theory and modeling. This then enables more complete understanding of the
      factors that must be controlled to achieve consistent and desirable outcomes.

PMID- 29457711
TI  - Small Animal Models for Evaluating Filovirus Countermeasures.
AB  - The development of novel therapeutics and vaccines to treat or prevent disease
      caused by filoviruses, such as Ebola and Marburg viruses, depends on the
      availability of animal models that faithfully recapitulate clinical hallmarks of
      disease as it is observed in humans. In particular, small animal models (such as
      mice and guinea pigs) are historically and frequently used for the primary
      evaluation of antiviral countermeasures, prior to testing in nonhuman primates,
      which represent the gold-standard filovirus animal model. In the past several
      years, however, the filovirus field has witnessed the continued refinement of the
      mouse and guinea pig models of disease, as well as the introduction of the
      hamster and ferret models. We now have small animal models for most human
      pathogenic filoviruses, many of which are susceptible to wild type virus and
      demonstrate key features of disease, including robust virus replication,
      coagulopathy, and immune system dysfunction. Although none of these small animal
      model systems perfectly recapitulates Ebola virus disease or Marburg virus
      disease on its own, collectively they offer a nearly complete set of tools in
      which to carry out the preclinical development of novel antiviral drugs.

PMID- 29457712
TI  - Strong Electrochemiluminescence from MOF Accelerator Enriched Quantum Dots for
      Enhanced Sensing of Trace cTnI.
AB  - The development of a sensitive and practical electrochemiluminescence (ECL)
      bioassay relies on the use of ECL signal tags whose signal intensity is high and
      stable. In this work, strong ECL emission was achieved from metal organic
      framework (MOF) accelerator enriched quantum dots (CdTe), which were applied as
      an efficient ECL signal tag for trace biomarker detection. It is particularly
      noteworthy that a novel mechanism to drastically enhance the ECL intensity of
      CdTe is established because isoreticular metal organic framework-3 (IRMOF-3) with
      2-amino terephthalic acid (2-NH2-BDC) as the organic ligand not only allows for
      loading a large amount of CdTe via the encapsulating effect and internal/external
      decoration but also functions as a novel coreactant accelerator for promoting the
      conversion of coreactant S2O82- into the sulfate radical anion (SO4*-), further
      boosting the ECL emission of CdTe. On the basis of the simple sandwich
      immunoreaction approach, cardiac troponin-I antigen (cTnI), a kind of biomarker
      related with myocardial infarction, was chosen as a detection model using an
      IRMOF-3-enriched CdTe labeled antibody as the signal probe. This immunosensor
      demonstrated desirable assay performance for cTnI with a wide response range from
      1.1 fg mL-1 to 11 ng mL-1 and a very low detection limit (0.46 fg mL-1). This
      suggested that the IRMOF-3-enriched CdTe nanocomposite strategy can integrate the
      coreactant accelerator and luminophore to significantly enhance the ECL intensity
      and stability, providing a direction for promising ECL tag preparation with broad
      applications.

PMID- 29457713
TI  - Probing Structural Changes among Analogous Inhibitor-Bound Forms of HIV-1
      Protease and a Drug-Resistant Mutant in Solution by Nuclear Magnetic Resonance.
AB  - In the era of state-of-the-art inhibitor design and high-resolution structural
      studies, detection of significant but small protein structural differences in the
      inhibitor-bound forms is critical to further developing the inhibitor. Here, we
      probed differences in HIV-1 protease (PR) conformation among darunavir and four
      analogous inhibitor-bound forms and compared them with a drug-resistant mutant
      using nuclear magnetic resonance chemical shifts. Changes in amide chemical
      shifts of wild-type (WT) PR among these inhibitor-bound forms, DeltaCSP, were
      subtle but detectable and extended >10 A from the inhibitor-binding site,
      asymmetrically between the two subunits of PR. Molecular dynamics simulations
      revealed differential local hydrogen bonding as the molecular basis of this
      remote asymmetric change. Inhibitor-bound forms of the drug-resistant mutant also
      showed a similar long-range DeltaCSP pattern. Differences in DeltaCSP values of
      the WT and the mutant (DeltaDeltaCSPs) were observed at the inhibitor-binding
      site and in the surrounding region. Comparing chemical shift changes among highly
      analogous inhibitors and DeltaDeltaCSPs effectively eliminated local
      environmental effects stemming from different chemical groups and enabled
      exploitation of these sensitive parameters to detect subtle protein
      conformational changes and to elucidate asymmetric and remote conformational
      effects upon inhibitor interaction.

PMID- 29457715
TI  - Embedding a Diketopyrrolopyrrole-Based Cross-linking Interfacial Layer Enhances
      the Performance of Organic Photovoltaics.
AB  - In this study, we prepared DPPBTDA, a diketopyrrolopyrrole-based small molecule
      presenting a terminal cross-linkable azido group, as a cathode modifying layer
      for organic photovoltaics (OPVs) having the inverted device structure
      glass/indium tin oxide/zinc oxide (ZnO) with or without the interfacial layer
      (IFL)/active layer/MoO3/Ag. The active layer comprising a blend of poly[4,8-bis(5
      (2-ethylhexyl)thien-2-yl)benzo[1,2- b;4,5- b']dithiophene-2,6-diyl- alt-(4-(2
      ethylhexyl)-3-fluorothieno[3,4- b]thiophene)-2-carboxylate-2,6-diyl] (PTB7-Th) as
      the electron donor and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) as the
      electron acceptor. Atomic force microscopy, space-charge-limited current
      mobility, surface energy, electron spectroscopy for chemical analysis depth
      profile, ultraviolet photoelectron spectroscopy analysis, and OPV performance
      data revealed that the surface status of ZnO changed after inserting the
      DPPBTDA/PCBM hybrid IFL and induced an optimized blend morphology, having a
      preferred gradient distribution of the conjugated polymer and PC71BM, for
      efficient carrier transport. The power conversion efficiency (AM 1.5 G, 1000 W m
      2) of the device incorporating the hybrid IFL increased to 9.4 +/- 0.11% from 8.5
      +/- 0.15% for the preoptimized PTB7-Th/PCBM device (primarily because of an
      enhancement in the fill factor from 68.7 +/- 1.1 to 72.1 +/- 0.8%).

PMID- 29457714
TI  - Selective Recognition of RNA Substrates by ADAR Deaminase Domains.
AB  - Adenosine deamination is one of the most prevalent post-transcriptional
      modifications in mRNA and is catalyzed by ADAR1 and ADAR2 in humans. ADAR1 and
      ADAR2 have different substrate selectivity, which is believed to mainly originate
      from the proteins' deaminase domains (hADAR1d and hADAR2d, respectively). RNA-seq
      of the Saccharomyces cerevisiae transcriptome subjected to ADAR-catalyzed RNA
      editing identified substrates with common secondary structure features
      preferentially edited by hADAR1d over hADAR2d. The relatively small size and
      efficient reaction of one of these substrates suggested it could be useful for
      further study of the hADAR1d reaction. Indeed, a short hairpin stem from the S.
      cerevisiae HER1 mRNA was efficiently deaminated by hADAR1d and used to generate
      an hADAR1d-specific fluorescent reporter of editing activity. Using substrates
      preferred by either hADAR1d or hADAR2d in vitro, we found that a chimeric protein
      bearing an RNA-binding loop from hADAR2d grafted onto hADAR1d showed ADAR2-like
      selectivity. Finally, a high-throughput mutagenesis analysis (Sat-FACS-Seq) of
      conserved residues in an RNA-binding loop of hADAR1d revealed essential amino
      acids for function, advancing our understanding of RNA recognition by this
      domain.

PMID- 29457716
TI  - Metal versus Ligand Reduction in Ln3+ Complexes of a Mesitylene-Anchored
      Tris(Aryloxide) Ligand.
AB  - The synthesis of 4f n Ln3+ complexes of the tris(aryloxide) mesitylene ligand,
      ((Ad,MeArO)3mes)3-, with Ln = La, Ce, Pr, Sm, and Yb, and their reduction with
      potassium have revealed that this ligand system can be redox active with some
      metals. Protonolysis of [Ln(N(SiMe3)2)3] (Ln = La, Ce, Pr, Sm, Yb) with the
      tris(phenol) (Ad,MeArOH)3mes yielded the Ln3+ complexes [((Ad,MeArO)3mes)Ln] (Ln
      = La, Ce, Pr, Sm, Yb), 1-Ln. Single electron reduction of each 4f n complex, 1
      Ln, using potassium yielded the reduced products, [K(2.2.2
      cryptand)][((Ad,MeArO)3mes)Ln] (Ln = La, Ce, Pr, Sm, Yb), 2-Ln. The Sm and Yb
      complexes have properties consistent with the presence of Ln2+ ions with
      traditional 4f n+1 electron configurations. However, the La, Ce, and Pr complexes
      appear to formally contain Ln3+ ions and ((Ad,MeArO)3mes)4- ligands. Structural
      comparisons of the [((Ad,MeArO)3mes)Ln] and [((Ad,MeOAr)3mes)Ln]1- complexes
      along with UV-vis absorption and EPR spectroscopy as well as density functional
      theory calculations support these ground state assignments.

PMID- 29457717
TI  - Oedometric Small-Angle Neutron Scattering: In Situ Observation of Nanopore
      Structure During Bentonite Consolidation and Swelling in Dry and Hydrous CO2
      Environments.
AB  - Results of oedometric consolidation experiments linked with small-angle neutron
      scattering (SANS) measurements are presented, using SWy-2 Wyoming bentonite clay
      in dry and water-bearing N2 and CO2 atmospheres. Oedometric SANS involves
      deforming a porous sample under uniaxial strain conditions with applied axial
      force and internal pore pressure control, and combines with SANS for in situ
      observation of pore structure evolution and interaction. Scattering from both
      interlayer (clay intra-aggregate) and free (interaggregate) pores is observed,
      showing decreasing pore size with dry consolidation and interactions between
      interlayer and free pore types with swelling and consolidation. Introduction of
      dry liquid CO2 at zero effective stress (axial stress minus pore pressure)
      produces large shifts in interlayer scatterers, but is reversible back to pre-CO2
      levels upon decreasing pore pressure and increasing effective stress.
      Introduction of wet liquid CO2, conversely, produces large but irreversible
      changes in interlayer scatterers, which are interpreted to be the combined result
      of CO2 and H2O intercalation under hydrostatic conditions, but which diminish
      with application of effective pressure and consolidation to higher bentonite dry
      densities. Consideration of CO2 intercalation in smectite-bearing CO2 caprocks
      needs to include effects of both water and nonhydrostatic stress.

PMID- 29457718
TI  - Lithium Amino Alkoxide-Evans Enolate Mixed Aggregates: Aldol Addition with
      Matched and Mismatched Stereocontrol.
AB  - Building on structural and mechanistic studies of lithiated enolates derived from
      acylated oxazolidinones (Evans enolates) and chiral lithiated amino alkoxides, we
      found that amino alkoxides amplify the enantioselectivity of aldol additions. The
      pairing of enantiomeric series affords matched and mismatched
      stereoselectivities. The structures of mixed tetramers showing 2:2 and 3:1
      (alkoxide-rich) stoichiometries are determined spectroscopically. Rate and
      computational studies provide a viable mechanistic and stereochemical model based
      on the direct reaction of the 3:1 mixed tetramers, but they raise unanswered
      questions for the 2:2 mixed aggregates.

PMID- 29457719
TI  - Fabrication of BSA@AuNC-Based Nanostructures for Cell Fluoresce Imaging and
      Target Drug Delivery.
AB  - Drug delivery which can offer efficient and localized drug transportation
      together with imaging capabilities is highly demanded in the development of
      cancer theranostic approaches. Herein, we report the construction of bovine serum
      albumin (BSA) gold nanoclusters (BSA@AuNCs) for cell fluoresce imaging and target
      drug delivery. BSA@AuNCs were modified with cyclic arginine-glycine-aspartate
      with the product RGD-BSA@AuNCs to enhance cell internalization of the
      nanoclusters. Furthermore, doxorubicin hydrochloride or doxorubicin (DOX), a
      widely used chemotherapy drug, was also used to modify RGD-BSA@AuNCs. The final
      design of the DOX/RGD-BSA@AuNC system was constructed through the disulfide bond.
      The physical microstructure and biological characterization of the BSA@AuNCs were
      realized through high-resolution transmission electron microscopy and confocal
      laser fluorescence microscopy. As the disulfide bonds were cleaved by glutathione
      in cancer cells, DOX-SH molecules were released from the nanosystem to inhibit
      the growth of cancer cells. The as-prepared DOX/RGD-BSA@AuNC system can be used
      not only to deliver drug but also to achieve the antitumor effect by in vivo
      imaging, demonstrating its promising applications in cancer treatment.

PMID- 29457720
TI  - Anion- and Solvent-Induced Single-Crystal-to-Single-Crystal Transformation within
      an Iron(II) Triazole System: a Promising Luminescent Probe for CrO42- and Cyano
      Containing Molecules.
AB  - Anion- and solvent-induced single-crystal-to-single-crystal transformation within
      an iron(II) triazole system has been generated from {[Fe(TPPT)2Cl2].CHCl3} n (1a)
      to [Fe(TPPT)(C2O4)0.5Cl(H2O)] n (1b). Luminescence studies indicated that the
      resultant 1b can be considered as a promising luminescent probe for CrO42- and
      cyano molecules.

PMID- 29457721
TI  - Reconstructing Dynamic Promoter Activity Profiles from Reporter Gene Data.
AB  - Accurate characterization of promoter activity is important when designing
      expression systems for systems biology and metabolic engineering applications.
      Promoters that respond to changes in the environment enable the dynamic control
      of gene expression without the necessity of inducer compounds, for example.
      However, the dynamic nature of these processes poses challenges for estimating
      promoter activity. Most experimental approaches utilize reporter gene expression
      to estimate promoter activity. Typically the reporter gene encodes a fluorescent
      protein that is used to infer a constant promoter activity despite the fact that
      the observed output may be dynamic and is a number of steps away from the
      transcription process. In fact, some promoters that are often thought of as
      constitutive can show changes in activity when growth conditions change. For
      these reasons, we have developed a system of ordinary differential equations for
      estimating dynamic promoter activity for promoters that change their activity in
      response to the environment that is robust to noise and changes in growth rate.
      Our approach, inference of dynamic promoter activity (PromAct), improves on
      existing methods by more accurately inferring known promoter activity profiles.
      This method is also capable of estimating the correct scale of promoter activity
      and can be applied to quantitative data sets to estimate quantitative rates.

PMID- 29457722
TI  - Spatially and Temporally Resolved Detection of Arsenic in a Capillary Dielectric
      Barrier Discharge by Hydride Generation High-Resolved Optical Emission
      Spectrometry.
AB  - A new method for arsenic detection by optical emission spectrometry (OES) is
      presented. Arsine (AsH3) is generated from liquid solutions by means of hydride
      generation (HG) and introduced into a capillary dielectric barrier discharge
      (DBD) where it is atomized and excited. A great challenge in OES is the reduction
      of the recorded background signal, because it negatively affects the limit of
      detection (LOD). In conventional DBD/OES methods, the signal intensity of the
      line of interest, in this case arsenic, is integrated over a long time scale.
      However, due to the pulsed character of the plasma, the plasma on-time is only a
      small fraction of the integration time. Therefore, a high amount of noise is
      added to the actual signal in each discharge cycle. To circumvent this, in the
      present study the emitted light from the DBD is collected by a fast gated iCCD
      camera, which is mounted on a modified monochromator. The experimental
      arrangement enables the recording of the emission signal of arsenic in the form
      of a monochromatic 2D-resolved picture. The temporal resolution of the iCCD
      camera in the nanosecond range provides the information at which point in time
      and how long arsenic is excited in the discharge. With use of this knowledge, it
      is possible to integrate only the arsenic emission by temporally isolating the
      signal from the background. With the presented method, the LOD for arsenic could
      be determined to 93 pg mL-1 with a calibration curve linear over 4 orders of
      magnitude. As a consequence, the developed experimental approach has a potential
      for both mechanistic studies of arsine atomization and excitation in DBD plasmas
      as well as routine applications, in which arsenic determination at ultratrace
      levels is required.

PMID- 29457723
TI  - Accurate Quantum Wave Packet Study of the Deep Well D+ + HD Reaction: Product Ro
      vibrational State-Resolved Integral and Differential Cross Sections.
AB  - The H+ + H2 reaction and its isotopic variants as the simplest triatomic ion
      molecule reactive system have been attracting much interests, however there are
      few studies on the titled reaction at state-to-state level until recent years. In
      this work, accurate state-to-state quantum dynamics studies of the titled
      reaction have been carried out by a reactant Jacobi coordinate-based time
      dependent wave packet approach on diabatic potential energy surfaces constructed
      by Kamisaka et al. Product ro-vibrational state-resolved information has been
      calculated for collision energies up to 0.2 eV with maximal total angular
      momentum J = 40. The necessity of including all K-component for accounting the
      Coriolis coupling for the reaction has been illuminated. Competitions between the
      two product channels, (D+ + HD' -> D'+ + HD and D+ + HD' -> H+ + DD') were
      investigated. Total integral cross sections suggest that resonances enhance the
      reactivity of channel D+ + HD'-> H+ + DD', however, resonances depress the
      reactivity of the another channel D+ + HD' -> D'+ + HD. The structures of the
      differential cross sections are complicated and depend strongly on collision
      energies of the two channels and also on the product rotational states. All of
      the product ro-vibrational state-resolved differential cross sections for this
      reaction do not exhibit rigorous backward-forward symmetry which may indicate
      that the lifetimes of the intermediate resonance complexes should not be that
      long. The dynamical observables of this deuterated isotopic reaction are quite
      different from the reaction of H+ + H2 -> H2 + H+ reported previously.

PMID- 29457724
TI  - Regio- and Stereoselective Synthesis of Isoindolin-1-ones through BuLi-Mediated
      Iodoaminocyclization of 2-(1-Alkynyl)benzamides.
AB  - A simple and straightforward synthesis of isoindolin-1-ones is reported.
      Exclusive N-cyclization of the amide functional group, an ambident nucleophile,
      was accomplished for the cyclization of 2-(1-alkynyl)benzamides using n-BuLi
      I2/ICl. The methodology works with the primary amide and affords the desired
      isoindolinones in yields of 38-94%. Interestingly, the isolated products exhibit
      a Z-stereochemistry across the C?C double bond. The reaction mechanism involving
      the formation of either a vinylic anion or an intimate ion pair intermediate is
      proposed.

PMID- 29457725
TI  - Accumulation of Citrulline by Microbial Arginine Metabolism during Alcoholic
      Fermentation of Soy Sauce.
AB  - Citrulline, the major precursor of ethyl carbamate in soy sauce, is an
      intermediate catabolite of arginine produced by bacteria present in soy sauce
      moromi mash. Pediococcus acidilactici is responsible for the formation of
      citrulline during the lactic acid fermentation process of soy sauce. However,
      citrulline accumulation during the alcoholic fermentation process and the
      corresponding bacteria involved have not been identified. Salt-tolerant, arginine
      utilizing bacteria were isolated from moromi mash during the alcoholic
      fermentation process. Under normal cultivation conditions, arginine utilization
      by these strains did not contribute to citrulline accumulation. However, the
      conversion of arginine to citrulline by these bacteria increased when cultivated
      during the alcoholic fermentation process. Additionally, the ethanol-enhanced
      solubility of free fatty acids in moromi mash stimulated the accumulation of
      citrulline. Staphylococcus exhibited the highest capability in the conversion of
      arginine to citrulline.

PMID- 29457726
TI  - A Robust Oil-in-Oil Emulsion for the Nonaqueous Encapsulation of Hydrophilic
      Payloads.
AB  - Compartmentalized structures widely exist in cellular systems (organelles) and
      perform essential functions in smart composite materials (microcapsules,
      vasculatures, and micelles) to provide localized functionality and enhance
      materials' compatibility. An entirely water-free compartmentalization system is
      of significant value to the materials community as nonaqueous conditions are
      critical to packaging microcapsules with water-free hydrophilic payloads while
      avoiding energy-intensive drying steps. Few nonaqueous encapsulation techniques
      are known, especially when considering just the scalable processes that operate
      in batch mode. Herein, we report a robust oil-in-oil Pickering emulsion system
      that is compatible with nonaqueous interfacial reactions as required for
      encapsulation of hydrophilic payloads. A major conceptual advance of this work is
      the notion of the partitioning inhibitor-a chemical agent that greatly reduces
      the payload's distribution between the emulsion's two phases, thus providing
      appropriate conditions for emulsion-templated interfacial polymerization. As a
      specific example, an immiscible hydrocarbon-amine pair of liquids is emulsified
      by the incorporation of guanidinium chloride (GuHCl) as a partitioning inhibitor
      into the dispersed phase. Polyisobutylene (PIB) is added into the continuous
      phase as a viscosity modifier for suitable modification of interfacial
      polymerization kinetics. The combination of GuHCl and PIB is necessary to yield a
      robust emulsion with stable morphology for 3 weeks. Shell wall formation was
      accomplished by interfacial polymerization of isocyanates delivered through the
      continuous phase and polyamines from the droplet core. Diethylenetriamine (DETA)
      loaded microcapsules were isolated in good yield, exhibiting high thermal and
      chemical stabilities with extended shelf-lives even when dispersed into a
      reactive epoxy resin. The polyamine phase is compatible with a variety of basic
      and hydrophilic actives, suggesting that this encapsulation technology is
      applicable to other hydrophilic payloads such as polyols, aromatic amines, and
      aromatic heterocyclic bases. Such payloads are important for the development of
      extended pot or shelf life systems and responsive coatings that report, protect,
      modify, and heal themselves without intervention.

PMID- 29457727
TI  - Epitaxial Growth of Flat Antimonene Monolayer: A New Honeycomb Analogue of
      Graphene.
AB  - Group-V elemental monolayers were recently predicted to exhibit exotic physical
      properties such as nontrivial topological properties, or a quantum anomalous Hall
      effect, which would make them very suitable for applications in next-generation
      electronic devices. The free-standing group-V monolayer materials usually have a
      buckled honeycomb form, in contrast with the flat graphene monolayer. Here, we
      report epitaxial growth of atomically thin flat honeycomb monolayer of group-V
      element antimony on a Ag(111) substrate. Combined study of experiments and
      theoretical calculations verify the formation of a uniform and single-crystalline
      antimonene monolayer without atomic wrinkles, as a new honeycomb analogue of
      graphene monolayer. Directional bonding between adjacent Sb atoms and weak
      antimonene-substrate interaction are confirmed. The realization and investigation
      of flat antimonene honeycombs extends the scope of two-dimensional atomically
      thick structures and provides a promising way to tune topological properties for
      future technological applications.

PMID- 29457728
TI  - Modification of the Electrolyte/Electrode Interface for the Template-free
      Electrochemical Synthesis of Metal Nanowires from Ionic Liquids.
AB  - In electrochemistry, the electrode/electrolyte interface (EEI) governs the
      charge/mass-transfer processes and controls the nucleation/growth phenomena. The
      EEI in ionic liquids (ILs) can be controlled by changing the cation/anion of the
      IL, salt concentration, electrode potential, and temperature. Here, we show that
      adding a dopant salt leads to the deposition of nanowires. To illustrate, zinc
      nanowires were electrodeposited from ZnCl2/1-butyl-1-methylpyrrolidinium
      trifluoromethylsulfonate in the presence of GaCl3 as a dopant salt. The choice of
      Zn salt and its ratio to GaCl3 were found to be crucial for Zn nanowires
      formation. AFM studies revealed that the solvation structure of Au(111)/IL
      changes significantly in the presence of GaCl3 and ZnCl2. Chronoamperometry
      showed changes in the nucleation/growth process, consequently leading to the
      formation of nanowires. A similar approach was adopted to synthesize Sn
      nanowires. Thus, modification of the EEI by adding a dopant to ILs can be a
      viable method to obtain nanowires.

PMID- 29457729
TI  - Assessing Interactions Between a Polytopic Membrane Protein and Lipid Bilayers
      Using Differential Scanning Calorimetry and Solid-State NMR.
AB  - It is known that the lipid composition within a cellular membrane can influence
      membrane protein structure and function. In this Article, we investigated how
      structural changes to a membrane protein upon substrate binding can impact the
      lipid bilayer. To carry out this study, we reconstituted the secondary active
      drug transporter EmrE into a variety of phospholipid bilayers varying in
      headgroup and chain length and carried out differential scanning calorimetry
      (DSC) and solid-state NMR experiments. The DSC results revealed a difference in
      cooperativity of the lipid phase transition for drug-free EmrE protonated at
      glutamic acid 14 (i.e., proton-loaded form) and the tetraphenylphosphonium (TPP+)
      bound form of the protein (i.e., drug-loaded form). To complement these findings,
      we acquired magic-angle-spinning (MAS) spectra in the presence and absence of
      TPP+ by directly probing the phospholipid headgroup using 31P NMR. These spectra
      showed a reduction in lipid line widths around the main phase transition for
      samples where EmrE was bound to TPP+ compared to the drug free form. Finally, we
      collected oriented solid-state NMR spectra on isotopically enriched EmrE that
      displayed chemical shift perturbations to both transmembrane and loop residues
      upon TPP+ binding. All of these results prompt us to propose a mechanism whereby
      substrate-induced changes to the structural dynamics of EmrE alters the
      surrounding lipids within the bilayer.

PMID- 29457730
TI  - Cryospectroscopy Studies of Intact Light-Harvesting Antennas Reveal Empirical
      Electronic Energy Transitions in Two Cyanobacteria Species.
AB  - Understanding of electronic energy transition (EET) mechanisms from the light
      harvesting unit to the reaction center in a natural system has been limited by
      (a) the use of conventional transient time-resolved spectroscopy at room
      temperature, which result in high signal-to-noise ratio and (b) examining
      extracts instead of intact light-harvesting units. Here, we report previously
      unknown differences and new insight in EET of two cyanobacteria species,
      Acaryochloris marina and Thermosynechoccocus vulcanus, which have been found only
      after using UV-vis, hole-burning, and fluorescence spectroscopy at ultralow
      temperature and examining their intact light-harvesting unit, phycobilisomes
      (PBS). Although the exciton formation is similarly induced by photoexcitation of
      chromophore assemblies in phycocyanin (PC) and allophycocyanin (APC) in PBSs of
      both species, the EET mechanisms are totally different, being adiabatic in A.
      marina and nonadiabatic in T. vulcanus. The PBS of A. marina has only one APC
      trimer and energy transfer is through coupling of alpha84 in APC with beta84 in
      adjacent PC. In T. vulcanus, the PBS has three components: coupling between APC
      core and the entire PC rod and couplings of beta-beta18 and of LCM to beta in the
      adjacent APC-like trimer. A total of 80% of the excitation energy is trapped in
      the coupling beta-beta18 and regulates the flow of energy from the high- to low
      level terminal electronic transition emitter beta-LCM. All these details cannot
      be observed at room temperature and in extracted units.

PMID- 29457731
TI  - Synthesis of Structurally Diverse Emissive Molecular Rotors with Four-Component
      Ugi Stators.
AB  - The use of the multicomponent Ugi reaction to rapidly prepare a library of
      dumbbell-like molecular rotors is highlighted here. The synthetic strategy
      consisted of the atom-economic access to 15 bulky and structurally diverse
      iodinated stators, which were cross-coupled to the 1,4-diethynylphenylene
      rotator. From those experiments, up to six rotors 1a-c and 1l-n were obtained,
      with yields ranging from 35 to 69% per coupled C-C bond. In addition to the
      framework diversity, five of these compounds showed aggregate-enhanced emission
      properties thanks to their conjugated 1,4-bis(phenylethynyl)benzene cores, a
      property that rises by increasing the water fraction (fw) in their THF solutions.
      The results highlight the significance of the diversity-oriented synthesis of
      rapid access to new molecular fluorescent rotors.

PMID- 29457732
TI  - Total Synthesis of Plusbacin A3 and Its Dideoxy Derivative Using a Solvent
      Dependent Diastereodivergent Joullie-Ugi Three-Component Reaction.
AB  - Full details of our synthetic studies toward plusbacin A3 (1), which is a
      depsipeptide with antibacterial activity, and its dideoxy derivative are
      described. To establish an efficient synthetic route of 1, a solvent-dependent
      diastereodivergent Joullie-Ugi three-component reaction (JU-3CR) was used to
      construct trans-Pro(3-OH) in a small number of steps. Two strategies were
      investigated toward the total synthesis. In the first synthetic strategy, the key
      steps were the trans-selective JU-3CR and a macrolactonization at the final stage
      of the synthesis. The JU-3CR using alkyl isocyanides in 1,1,1,3,3,3
      hexafluoroisopropanol provided the trans products, and the coupling of the
      fragments to prepare the macrocyclization precursor proceeded smoothly. However,
      attempts toward the macrolactonization did not provide the desired product. Then,
      the second strategy that included esterification in an initial stage was
      investigated. Methods for constructing trans-Pro(3-OH) were examined using a
      convertible isocyanide, which could be converted to a carboxylic acid required
      for the following amidation. Ester bond formation was achieved through an
      intermolecular coupling using a hydroxyl-Asp derivative and the corresponding
      alcohol, and the amidation afforded a linear depsipeptide. The macrolactamization
      of the linear peptide gave the cyclic depsipeptide, and then the global
      deprotection accomplished the total synthesis of 1 and its dideoxy derivative.

PMID- 29457733
TI  - Fe(III)-Catalyzed Hydroallylation of Unactivated Alkenes with Morita-Baylis
      Hillman Adducts.
AB  - An Fe(III)-catalyzed hydroallylation of unactivated alkenes with Morita-Baylis
      Hillman adducts via an Fe-catalyzed process is described. A variety of alkenes,
      including mono-, di-, and trisubstituted alkenes, could all smoothly convert to
      structural diversified cinnamates in this protocol. Interestingly, when the
      hydroxyl-containing alkenes were used, various lactones could be rapidly
      assembled. Moreover, this protocol could be applied to late-stage
      functionalization of natural products.

PMID- 29457734
TI  - Role of nutrient limitation in the competition between uropathogenic strains of
      Klebsiella pneumoniae and Escherichia coli in mixed biofilms.
AB  - Klebsiella pneumoniae and Escherichia coli form mixed species biofilms in
      catheter-associated urinary tract infections. Recently, a detrimental effect of
      K. pneumoniae over E. coli was observed in mixed species biofilms grown in an
      artificial urine medium. The mechanism behind this competitive interaction was
      studied. K. pneumoniae partially outcompeted E. coli in early-stage batch-fed
      biofilms, whereas both microorganisms co-exist at longer times (K. pneumoniae:E.
      coli ratio, 55:1), as shown by cell counts and confocal microscopy. E. coli cells
      were scattered along the K. pneumoniae biofilm. Biofilm supernatants did not
      appear to contain either antimicrobial or anti-biofilm activities against E.
      coli. Biofilms grown under continuous flow prevented interspecies competition. K.
      pneumoniae showed both increased siderophore production and better growth in iron
      limited media compared to E. coli. In summary, these results indicate the
      importance of nutrient (particularly iron) competition in the modulation of the
      bacterial composition of mixed species biofilms formed by uropathogenic K.
      pneumoniae and E. coli.

PMID- 29457735
TI  - Bio-guided isolation of Centaurea bruguierana subsp. belangerana cytotoxic
      components.
AB  - Centaurea bruguierana subsp. belangerana was extracted by 80% ethanol. The total
      extract was then partitioned into four fractions including chloroform, ethyl
      acetate and methanol. Cytotoxic effect of fractions was examined by MTT assay in
      K562 (chronic myelogenous leukemia), AGS (gastric adenocarcinoma), MCF-7 (breast
      adenocarcinoma) and SW742 (colon adenocarcinoma) cell lines. The Chloroform
      fraction, with the lowest LC50 against K-562 cell lines, was partitioned into 14
      subfractions and subjected to further purification by reversed-phase (C18) silica
      gel and sephadex LH-20 column chromatography. Three flavonoids including
      cirsimaritin, cirsilinelol and eupatilin were isolated for the first time from
      the species and the structures were confirmed by spectroscopic data. The high
      selectivity index of the purified flavonoids indicates valuable components with
      potential few side effects for normal cell lines. However, solubility tests for
      isolated components indicates the need for novel pharmaceutical dosage forms, in
      the case for using natural flavonoids as chemotherapeutic agents.

PMID- 29457736
TI  - Answer to the letter of Marge Berer.

PMID- 29457737
TI  - Determining the Value of Cerebrospinal Fluid Lactate Dehydrogenase Level in
      Differentiating Subarachnoid Hemorrhage From Traumatic Lumbar Puncture.
AB  - Context Lumbar puncture (LP) is still an important modality in the diagnosis of
      subarachnoid hemorrhage (SAH). Rapid and correct fluid analysis can provide
      patients with a better prognosis by appropriate intervention. Objective To
      determine the value of cerebrospinal fluid lactate dehydrogenase level in
      differentiation between SAH and traumatic LP. Design This was a cross-sectional
      observational study. Patients with a diagnostic suspicion of SAH who were
      admitted to the emergency department were enrolled in our study based on the
      inclusion criteria. All patients underwent head computed tomography scan without
      contrast. Patients with SAH confirmed on computed tomography scan and those who
      needed surgical intervention underwent LP by the neurosurgical service in the
      operation room (group 1). Other patients who fulfilled the inclusion criteria but
      had a traumatic LP in the emergency setting were also enrolled in our study
      (group 2). The fluid samples of all LPs were sent to the laboratory to be
      analyzed. Finally, we compared the results of the 2 groups with each other.
      Results Fifty-two patients were enrolled in our study, 26 patients (50%) from
      each group. The cerebrospinal fluid lactate dehydrogenase level was significantly
      higher in group 1 than it was in group 2 ( P < .001), and based on receiver
      operating characteristic curve analysis, the significant level of cerebrospinal
      fluid lactate dehydrogenase to differentiate SAH from traumatic LP was estimated
      to be 185. The red blood cell and white blood cell counts were significantly
      higher in group 1 than they were in group 2 ( P < .001). Conclusions
      Cerebrospinal fluid lactate dehydrogenase can effectively differentiate SAH from
      traumatic tap in LP samples.

PMID- 29457738
TI  - Reproducibility and Feasibility of Strategies for Morphologic Assessment of Renal
      Biopsies Using the Nephrotic Syndrome Study Network Digital Pathology Scoring
      System.
AB  - Context Testing reproducibility is critical for the development of methodologies
      for morphologic assessment. Our previous study using the descriptor-based
      Nephrotic Syndrome Study Network Digital Pathology Scoring System (NDPSS) on
      glomerular images revealed variable reproducibility. Objective To test
      reproducibility and feasibility of alternative scoring strategies for digital
      morphologic assessment of glomeruli and explore use of alternative agreement
      statistics. Design The original NDPSS was modified (NDPSS1 and NDPSS2) to
      evaluate (1) independent scoring of each individual biopsy level, (2) use of
      continuous measures, (3) groupings of individual descriptors into classes and
      subclasses prior to scoring, and (4) indication of pathologists'
      confidence/uncertainty for any given score. Three and 5 pathologists scored 157
      and 79 glomeruli using the NDPSS1 and NDPSS2, respectively. Agreement was tested
      using conventional (Cohen kappa) and alternative (Gwet agreement coefficient 1
      [AC1]) agreement statistics and compared with previously published data (original
      NDPSS). Results Overall, pathologists' uncertainty was low, favoring application
      of the Gwet AC1. Greater agreement was achieved using the Gwet AC1 compared with
      the Cohen kappa across all scoring methodologies. Mean (standard deviation)
      differences in agreement estimates using the NDPSS1 and NDPSS2 compared with the
      single-level original NDPSS were -0.09 (0.17) and -0.17 (0.17), respectively.
      Using the Gwet AC1, 79% of the original NDPSS descriptors had good or excellent
      agreement. Pathologist feedback indicated the NDPSS1 and NDPSS2 were time
      consuming. Conclusions The NDPSS1 and NDPSS2 increased pathologists' scoring
      burden without improving reproducibility. Use of alternative agreement statistics
      was strongly supported. We suggest using the original NDPSS on whole slide images
      for glomerular morphology assessment and for guiding future automated
      technologies.

PMID- 29457739
TI  - Scutellarein from Scutellaria barbata induces apoptosis of human colon cancer
      HCT116 cells through the ROS-mediated mitochondria-dependent pathway.
AB  - To search novel therapy for human colon cancer, scutellarein identified from
      Scutellaria barbata was investigated using HCT116 cells. As a result,
      scutellarein can induce apoptosis of HCT116 cells. Further investigation for the
      mechanism has revealed scutellarein can increase the production of intracellular
      ROS and lead to the collapse of mitochondrial membrane potential. Meanwhile, the
      activity of caspase-3 in HCT116 cells was elevated by scutellarein. Moreover,
      down-regulated Bcl-2 and up-regulated Bax were observed. Additionaly,
      scutellarein resulted in cytochrome c release from mitochondria. These results
      indicated the apoptosis induction of HCT116 cells by scutellarein was implemented
      through ROS-mediated mitochondria-dependent pathway.

PMID- 29457740
TI  - Comparison of the Use of Titanium-Zirconium Alloy and Titanium Alloy in Dental
      Implants: A Systematic Review and Meta-Analysis.
AB  - The aim of this study was to compare the values of bone-implant contact (BIC) and
      removal torque (RTQ) reported in different animal studies for titanium-zirconium
      (TiZr) and titanium (Ti) dental implants. This review has been registered at
      PROSPERO under number CRD42016047745. We undertook an electronic search for data
      published up until November 2017 using the PubMed/Medline, Embase, and The
      Cochrane Library databases. Eligibility criteria included in vivo studies,
      comparisons between Ti and TiZr implants in the same study, and studies published
      in English that evaluated BIC and RTQ. After inclusion criteria, 8 studies were
      assessed for eligibility. Of the 8 studies, 7 analyzed BIC outcome and 3 analyzed
      RTQ outcome. Among such studies, 6 studies were considered for meta-analysis of
      quantitative for BIC and 2 studies for RTQ. There was no significant difference
      for BIC analysis ( P = .89; random ration [RR]: -0.21; 95% confidence interval
      [CI]: -3.14 to 2.72). The heterogeneity of the primary outcome studies was
      considered low (7.19; P = .21; I 2 : 30%). However, the RTQ analysis showed
      different results favoring the TiZr dental implants ( P = .001; RR: 23.62; 95%CI:
      9.15 to 38.10). Low heterogeneity was observed for RTQ (chi2: 1.25; P = .26; I 2
      : 20%). Within the limitations of this study, there was no difference between
      TiZr and Ti alloys implants in terms of BIC. However, TiZr implants had higher
      RTQ than Ti alloys.

PMID- 29457741
TI  - Lucidumol D, a new lanostane-type triterpene from fruiting bodies of Reishi
      (Ganoderma lingzhi).
AB  - A new lanostane-type triterpenoid, lucidumol D (1) was isolated from the fruiting
      bodies of Ganoderma lingzhi. Its structure was elucidated on the basis of
      extensive 1D- and 2D-NMR studies as well as mass spectrometry. The cytotoxicity
      of lucidumol D against proliferation of several cancer cells were assayed by
      using MTT method and the obtained result suggested selective anti-proliferative
      and cytotoxic effects against MCF-7, HepG2, HeLa, Caco-2, and HCT-116. In
      comparison to lucidumol C (2) isolated previously by our group, the structure
      activity relationship indicated that carbonyl function at C-11 is necessary to
      enhance the cytotoxicity.

PMID- 29457742
TI  - Response to "Progesterone for preventing pregnancy termination after initiation
      of medical abortion with mifepristone": what's the real point here?

PMID- 29457743
TI  - A framework for complexity in palliative care: A qualitative study with patients,
      family carers and professionals.
AB  - BACKGROUND: Palliative care patients are often described as complex but evidence
      on complexity is limited. We need to understand complexity, including at
      individual patient-level, to define specialist palliative care, characterise
      palliative care populations and meaningfully compare interventions/outcomes. AIM:
      To explore palliative care stakeholders' views on what makes a patient more or
      less complex and insights on capturing complexity at patient-level. DESIGN: In
      depth qualitative interviews, analysed using Framework analysis.
      PARTICIPANTS/SETTING: Semi-structured interviews across six UK centres with
      patients, family, professionals, managers and senior leads, purposively sampled
      by experience, background, location and setting (hospital, hospice and
      community). RESULTS: 65 participants provided an understanding of complexity,
      which extended far beyond the commonly used physical, psychological, social and
      spiritual domains. Complexity included how patients interact with
      family/professionals, how services' respond to needs and societal perspectives on
      care. 'Pre-existing', 'cumulative' and 'invisible' complexity are further
      important dimensions to delivering effective palliative and end-of-life care. The
      dynamic nature of illness and needs over time was also profoundly influential.
      Adapting Bronfenbrenner's Ecological Systems Theory, we categorised findings into
      the microsystem (person, needs and characteristics), chronosystem (dynamic
      influences of time), mesosystem (interactions with family/health professionals),
      exosystem (palliative care services/systems) and macrosystem (societal
      influences). Stakeholders found it acceptable to capture complexity at the
      patient-level, with perceived benefits for improving palliative care resource
      allocation. CONCLUSION: Our conceptual framework encompasses additional elements
      beyond physical, psychological, social and spiritual domains and advances
      systematic understanding of complexity within the context of palliative care.
      This framework helps capture patient-level complexity and target resource
      provision in specialist palliative care.

PMID- 29457744
TI  - Optimal safe implantation corridors in feline cervical vertebrae (C2-T1): CT
      study in 16 domestic shorthair cats.
AB  - OBJECTIVES: The objective of this study was to define safe corridors for the
      optimal placement of bicortical implants in the feline cervical spine (C2-T1)
      using CT. METHODS: CT images of feline cervical spines (n = 16) were reviewed
      retrospectively. Multiplanar reconstructions were used to define the optimal safe
      corridors. Safe corridors were defined by their angle of insertion, width and
      length. The insertion point within the vertebral body was also described.
      Vertebral measurements were compared between vertebrae using multilevel linear
      regression, and left and right measurements within vertebrae were compared with
      the paired samples Wilcoxon signed-rank test. A P value <0.05 was considered
      significant for all analyses. RESULTS: The safe corridor insertion points were
      located within the caudal third of the vertebral body in C2 (mean cranial
      vertebral ratio 0.73) and in the cranial third of the vertebral bodies from C3-T1
      (mean cranial vertebral ratios 0.34-0.38). Mean safe corridor widths ranged from
      1.04 mm in C2 to 2.30 mm in C7 and T1. The mean right and left optimal angles of
      implantation were, respectively, 21.79 degrees  and 21.49 degrees  for C2, 45.26
      degrees  and 46.19 degrees  for C3, 51.48 degrees  and 51.04 degrees  for C4,
      53.52 degrees  and 54.30 degrees  for C5, 56.36 degrees  and 56.65 degrees  for
      C6, 63.40 degrees  and 64.92 degrees  for C7, and 53.90 degrees  and 52.90
      degrees  for T1. There were statistically significant differences between
      vertebrae in almost every measurement. CONCLUSIONS AND RELEVANCE: Cervical
      vertebral safe corridors in cats are narrow and differ to those reported in dogs.
      Safe corridors are located in the caudal third of C2 and cranial third of the C3
      T1 vertebral bodies. Current recommendations for implant sizes should be
      reviewed, as 1.5-2 mm implants would be oversized for bicortical implantation in
      most of the feline cervical vertebrae.

PMID- 29457745
TI  - Evaluation of mosquito larvicidal activity of fruit extracts of Acacia
      auriculiformis against the Japanese encephalitis vector Culex vishnui.
AB  - The larvicidal potentiality of crude and ethyl acetate extracts of fruits of
      Acacia auriculiformis was investigated against all the larval instars of JE
      vector Culex vishnui. The crude extracts showed good results against all the
      larval instars with highest mortality at 0.09%. Highest mortality was found at
      300 ppm of ethyl acetate extract. Lowest LC50 value was obtained at 72 h for
      third instar larvae. Non target organisms tested, showed no to very less
      mortality to ethyl acetate solvent extract. Presence of N-H stretching, a C=O
      stretching, C=C and C-N stretching vibrations of secondary amide or amine group
      were confirmed from IR analysis. GC-MS analysis revealed the presence of three
      compounds namely Ethane 2-chloro-1,1-dimethoxy, Acetic acid, 1-methyl ether ester
      and [4-[1-[3,5-Dimethyl-4[(trimethylsilyl)oxy)phenyl]-1,3-dimethylbutyl)
      2,6dimethylphenoxy)(trimethyl) silane, responsible for mosquito larval death.

PMID- 29457746
TI  - Cardiac rupture caused by traffic accident: Case reports and a literature review.
AB  - The commonest cause of blunt cardiac injuries is from traffic accidents followed
      by violent falls, sport activities, accidents or a fight but rupture of the heart
      is rare and lethal. The precise incidence of cardiac injury after a blunt chest
      trauma is unknown as rates vary greatly in the literature from between 7% and 76%
      of cases. Autopsy studies have shown that the right ventricle is the most
      frequently ruptured, followed by the left ventricle, right atrium,
      intraventricular septum, left atrium and interatrial septum with decreasing
      frequency. Post-mortem imaging is a rapidly advancing field of post-mortem
      investigations of trauma victims. The available literature dealing with the
      comparison of post-mortem computed tomography results with forensic autopsy
      indicates that conventional autopsy remains superior for the detection of organ
      and soft tissue injuries in all body regions.

PMID- 29457747
TI  - Lebbeckoside C, a new triterpenoid saponin from the stem barks of Albizia lebbeck
      inhibits the growth of human glioblastoma cells.
AB  - One new acacic acid-type saponin, named lebbeckoside C (1), was isolated from the
      stem barks of Albizia lebbeck. Its structure was established on the basis of
      extensive analysis of 1D and 2D NMR (1H, 13C NMR, DEPT, COSY, TOCSY, ROESY, HSQC
      and HMBC) experiments, HRESIMS studies, and by chemical evidence as 3-O-[beta-d
      xylopyranosyl-(l->2)-beta-d-fucopyranosyl-(1->6)-[beta-d-glucopyranosyl(1->2)]
      beta-d-glucopyranosyl]-21-O-{(2E,6S)-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(beta-d
      quinovopyranosyl)octa-2,7-dienoyl]-4-O-[(2E,6S)-2,6-dimethyl-6-O-(beta-d
      quinovopyranosyl)octa-2,7-dienoyl]-beta-d-quinovopyranosyl}-2,6-dimethylocta-2,7
      dienoyl}acacic acid 28 O-[beta-d-quinovopyranosyl-(l->3)-[alpha-l
      arabinofuranosyl-(l->4)]-alpha-l-rhamnopyranosyl-(l->2)-beta-d-glucopyranosyl]
      ester. The isolated saponin (1) displayed significant cytotoxic activity against
      the human glioblastoma cell line U-87 MG and TG1 stem-like glioma cells isolated
      from a patient tumor with IC50 values of 1.69 and 1.44 MUM, respectively.

PMID- 29457748
TI  - Structural determination of two new acacic acid-type saponins from the stem barks
      of Albizia zygia (DC.) J. F. Macbr.
AB  - As a continuation of our interest in the study of triterpenoid saponins from
      Albizia zygia, phytochemical investigation of its stem barks led to the isolation
      of two new oleanane-type saponins, named zygiaosides C-D (1-2). Their structures
      were established on the basis of extensive analysis of 1D and 2D NMR (1H-, 13C
      NMR, DEPT, COSY, TOCSY, ROESY, HSQC and HMBC) experiments, HRESIMS studies, and
      by chemical evidence as, 3-O-[ beta-d-glucopyranosyl-(1->2)-[alpha-l
      arabinopyranosyl-(1->6)]-beta-d-glucopyranosyl]-21-O-[(2E,6S)-2,6-dimethyl-6-O
      (beta-d-quinovopyranosyl) octa-2,7-dienoyl]acacic acid 28-O-alpha-l
      arabinofuranosyl-(1->4)-[beta-d-glucopyranosyl-(1->3)]-alpha-l-rhamnopyranosyl-(1
      >2)-beta-d-glucopyranosyl ester (1) and 3- O-[beta-d-glucopyranosyl-(1->2) -[
      beta-d-fucopyranosyl-(1->6)]-beta-d-glucopyranosyl]-21-O-[(2E,6S)-2,6-dimethyl-6
      O-(beta-D-quinovopyranosyl) octa-2,7-dienoyl]acacic acid 28-O-alpha-l
      arabinofuranosyl-(1->4)-[beta-d-glucopyranosyl-(1->3)]-alpha-l-rhamnopyranosyl-(1
      >2)-beta-d-glucopyranosyl ester (2).

PMID- 29457750
TI  - Chemical and biological evaluation of essential oil from Saussurea costus (Falc.)
      Lipsch. from Garhwal Himalaya collected at different harvesting periods.
AB  - The purpose of this study is the determination of chemical composition and
      antioxidant activity of essential oils (EOs) from Saussurea costus (Falc.)
      Lipsch. Roots have been collected on December of the first plant year (IY) and in
      April, August and December of the third plant year (I, 6B, D7). A GC analysis was
      carried out for achieving this purpose. Subsequently, total polyphenol content
      (TPC) and antioxidant activity measured by DPPH, FRAP and BCB assays were
      evaluated. Three different statistical methods: Relative Antioxidant Capacity
      Index (RACI), Pearson's correlation coefficient (r) and PCA, were used to compare
      results obtained and underline EO relationships. From the results obtained, it
      was possible to observe how the collection period of the EO, in particular both
      the month and the year of collection, influences the metabolite profile.

PMID- 29457749
TI  - Chemical and biological studies on Bridelia ferruginea grown in Nigeria.
AB  - Phytochemical investigation of the methanolic extract of dried leaves of Bridelia
      ferruginea led to the isolation and identification of fourteen compounds (1-14):
      compound 1 [mixture of palmitic, stearic and oleic acids], stearyl monoester of 2
      O-beta-?-glucosylglycerol (2), 6beta-hydroxy-(20R)-24-ethylcholest-4-en-3-one
      (3a), 6beta-hydroxy-(20R)-24-ethylcholest-4,22-dien-3-one (3b), lutein (4),
      vomifoliol (5), corilagin (6), kaempferide-3-O-beta-?-glucoside (7), myricetin
      (8), isomericitrin (9), isoquercetin (10), myricitrin (11), quercitrin (12),
      rutin (13), and beta-sitosterol glucoside (14). The total extract exhibited
      moderate activity towards CB2 receptor and 90% inhibition against leishmanial
      pathogen Trypanosoma brucei. Compound 4 exhibited 73% displacement in CB2
      receptor with IC50 56.47 MUM, and 93% inhibition towards T. brucei with IC50 4.16
      MUM. Compound 11 showed 99% inhibition towards Escherichia coli with IC50 1.123
      MUM.

PMID- 29457752
TI  - Accuracy and Bias in Perception of Distress Level and Distress Change Among Same
      Sex College Student Roommate Dyads.
AB  - University students often experience high levels of stress and, in some cases,
      the stress leads to tragic outcomes. An important question is whether roommates
      can perceive the level and change in distress in their peers. We examined self-
      and other-reports of 187 same-sex undergraduate dyads at two times in a spring
      semester. Using the truth and bias model, we found that roommates tended to
      underestimate their partner's distress at both time points, and that ratings were
      equally influenced by truth and self-focus bias forces. For change, however,
      there was no evidence of directional (average) bias, and perceived change was
      only significantly related to the truth force. There were no consistent
      moderation effects by closeness or gender. These findings are interpreted in the
      context of person perception theory and the practical need for early warning
      about extreme distress in college students.

PMID- 29457751
TI  - Intra- and inter-fraction uncertainties during IGRT for Wilms' tumor.
AB  - BACKGROUND AND PURPOSE: To assess intra- and inter-fraction motion uncertainties,
      due to displacements of the tumor bed (TB) and organs at risk (OAR), as well as
      intra- and inter-fraction patient set-up uncertainties, due to positioning
      variations, during image-guided radiation therapy (IGRT) in children with Wilms'
      tumor. MATERIAL AND METHODS: Four-dimensional computed tomography (4D-CT) and
      daily pre- and post-treatment cone-beam CT (CBCT)-scans of 15 patients (average
      4, range 1-8 years) undergoing flank irradiation after nephrectomy were analyzed.
      TB (marked by four surgical clips) and OAR motion uncertainties were quantified
      by displacements of the center of mass in all orthogonal directions.
      Translational and rotational bone off-sets were recorded for patient set-up
      uncertainties assessment in all orthogonal directions. The average results,
      systematic and random errors were computed. RESULTS: Average intra- and inter
      fraction motion uncertainties were <=1.1 mm (range: [-6.9;7.9] mm) for the TB and
      <=3.2 mm (range: [-9.1;9.6] mm) for the OAR. Average intra- and inter-fraction
      patient set-up uncertainties were <=0.1 mm (range: [-3.3;4.8] mm) and <=0.9
      degrees  (range: [0.0;2.8 degrees ]). Both motion and patient set-up
      uncertainties were larger for the cranio-caudal direction. Calculated systematic
      and random errors were <=2.4 mm for the motion uncertainties and <=0.8 mm/0.7
      degrees  for the patient set-up uncertainties. CONCLUSIONS: Average motion and
      patient set-up uncertainties during radiotherapy treatment were found to be
      limited. However, uncertainties were larger for the cranio-caudal direction and
      outliers were found in all orthogonal directions. When having available 4D-CT and
      CBCT information, the use of patient-specific and anisotropic safety margin
      expansions is advised for both target volume and OAR.

PMID- 29457753
TI  - Bone Strength and Exercise During Youth-The Year That Was 2017.
AB  - The positive effects of physical activity on bone strength are certain. However,
      researchers have yet to precisely quantify the contribution of specific
      characteristics of physical activity that affect bone strength in children and
      adolescents. This commentary highlights 2 noteworthy 2017 publications that
      addressed osteogenic physical activity dose-response issues. Both papers moved
      the field forward by providing new insights on physical activity exposures beyond
      high-impact loading. Koedijk et al's paper was selected because, to the best of
      our knowledge, it is the first systematic review to solely examine associations
      between sedentary behavior and indicators of bone strength. The second selected
      paper, Gabel et al, used novel approaches in accelerometer processing and
      statistical modeling to separate the osteogenic effects of frequency of short
      bouts of physical activity from total volume of physical activity. As such, the
      authors of this paper begin to explore in youth what animal models have shown for
      some time, that is, optimal bone adaptation requires the correct combination of
      intensity, frequency, duration, nonrepetitive movement, and rest. Together, these
      papers signal new and important approaches for the conceptualization,
      measurement, and interpretation of osteogenic physical activity.

PMID- 29457755
TI  - Novel approach for CES1 genotyping: integrating single nucleotide variants and
      structural variation.
AB  - AIM: Development of a specific procedure for genotyping of CES1A1 (CES1) and
      CES1A2, a hybrid of CES1A1  and the pseudogene CES1P1. MATERIALS & METHODS: The
      number of CES1A1 and CES1A2  copies and that of CES1P1  were determined using
      real-time PCR. Long range PCRs followed by secondary PCRs allowed sequencing of
      single nucleotide variants in CES1A1 and CES1A2. RESULTS & CONCLUSION: A
      procedure consisting of two main steps was developed. Its first main step, the
      copy number determination, informed about presence of CES1A2 . This information
      enabled choice of PCR in the second main step, which selectively amplified CES1A1
      and, if present, also CES1A2, for subsequent sequencing. Examination of 501 DNA
      samples suggested that our procedure is specific with potential for
      personalization of drug treatments.

PMID- 29457754
TI  - Effect of ship hull form on the resistance penalty from biofouling.
AB  - Hull biofouling is a well-known problem for the shipping industry, leading to
      increased resistance and fuel consumption. Considering that the effects of hull
      form on resistance are known to be higher for a less slender hull, it is
      hypothesised in this paper that the effect of biofouling roughness on resistance
      is also dependent on the hull form. To test this hypothesis, previously reported
      full-scale numerical results on a containership are re-analysed. Form effects on
      roughness penalties, corresponding to KDeltaCT = 0.058 +/- 0.025, are observed at
      a low speed (19 knots, Res = 2.29 * 109), which are however cancelled out by
      traditionally neglected roughness effects on wave-making resistance at a higher
      speed (24 knots, Res = 2.89 * 109). It is concluded that hull form effects on
      biofouling penalties can be significant at low speeds, though not generalisable
      for higher speeds, namely when wave-making resistance corresponds to >= 29% of
      total resistance.

PMID- 29457757
TI  - Structural variability of DNA-containing Mg-pyrophosphate microparticles:
      optimized conditions to produce particles with desired size and morphology.
AB  - Our previous studies demonstrated the formation of structurally diverse DNA
      containing microparticles (DNA MPs) in PCR with Mg-pyrophosphate (MgPPi) as the
      structure-forming component. These DNA MPs were referred to major structural
      types: microdisks (2D MPs) with nanometer thickness and 3D MPs with sophisticated
      morphology and constructed from intersecting disks and their segments. Little is
      known about factors that influence both the morphology and size of DNA MPs, and
      the present study was aimed at fulfilling this gap. We showed that the addition
      of Mn2+ cations to PCR mixtures caused the profound changes in MPs morphology,
      depending on DNA polymerase used (KlenTaq or Taq). Asymmetric PCR with 20-fold
      decrease in the concentration of one of two primers facilitated the predominant
      formation of microdisks with unusual structure. The addition of 1 mM Na
      pyrophosphate to PCR mixtures with synthesized DNA and subsequent thermal cycling
      (10-15 cycles) were optimal to produce microdisks or nanometer 3D particles.
      Using electron microscopy, we studied also the structure of inorganic micro- and
      nanoparticles from MgPPi, formed during multiple heating and cooling cycles of a
      mixture of Mg2+ and Na-pyrophosphate in various regimes. Also, we found the
      conditions to yield planar (Mg.Mn)PPi nanocrystals (diameter ~100 nm and
      thickness ~10 nm) which efficiently adsorbed exogenous DNA. These inorganic
      nanoparticles are promising for DNA delivery in transfection studies. Mechanisms
      to be involved in structural modifications of MPs and perspectives of their
      practical application are discussed.

PMID- 29457756
TI  - Effects of combined oral contraceptives on the clinical and biochemical
      parameters of hyperandrogenism in patients with polycystic ovary syndrome: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Nowadays, selection of COCs with maximum antiandrogenic effects is
      one the main issues in treatment of women with polycystic ovary syndrome (PCOS).
      OBJECTIVE: This systematic review and meta-analysis aimed to compare the effects
      of COCs on the clinical and biochemical parameters of hyperandrogenism (HA) in
      patients with PCOS. METHODS: Electronic databases (PubMed, Scopus, ScienceDirect
      and web of science) were searched from 1987 to November 2015 to identify clinical
      trials investigating effect of the various COCs on the clinical and biochemical
      parameters of HA in patients. In this meta-analysis, both fixed and random effect
      models were used. Potential sources of heterogeneity were explored by meta
      regression and subgroup analyses. RESULTS: Findings showed that COC use for 3-12
      months was significantly associated with an increase in sex hormone-binding
      globulin (SHBG) levels and a decrease in Ferriman-Gallwey (FG) score, total
      testosterone (TT), free testosterone (FT), androstenedione (A4) and
      dehydroepiandrosterone sulphate (DHEAS) levels. Type of progestin or duration of
      treatment had no important effects on declining androgen levels. Long-term use of
      COCs (6-12 months) was more effective in improving hirsutism, compared to short
      term. COCs containing cyproterone acetate (CPA) for 12 months had the strongest
      effect in improving hirsutism. CONCLUSIONS: This study shows that, in patients
      with PCOS, COCs can effectively improve biochemical and clinical parameters of
      HA. All COCs studies have similar effects on the hormonal profiles of these
      patients, and products containing CPA may be an effective treatment in hirsute
      patients with PCOS.

PMID- 29457758
TI  - Appraising cervical mucus: a new approach to evaluating contraceptives.
AB  - PURPOSE: Timing of sample collection represents a major source of variability in
      studies evaluating the effects of administered agents on cervical mucus in
      naturally-cycling women. We sought to create and validate an artificial model of
      the cervical mucus cycle using exogenous E2 and P4 replacement in ovarian
      suppressed women. MATERIALS AND METHODS: We conducted a prospective experiment
      (clinicaltrials.gov, NCT02969590) examining cervical mucus changes in six women
      during natural and artificial menstrual cycles [leuprolide acetate, estradiol
      transdermal patch (0.05-0.3 mg/day) and progesterone 200 mg/day]. We collected
      serum and mucus samples at each visit corresponding to early, mid and late
      follicular, ovulation and mid-luteal time points in the natural and artificial
      cycles. We evaluated mucus according to the modified Insler score described in
      the WHO laboratory Manual for the Examination and Processing of Human Semen.
      RESULTS: We enrolled healthy women between 27 and 40 years of age. All of the
      subjects achieved a mucus score of >=10 both in the natural cycle and during peak
      estradiol replacement levels (0.3 mg/day) in the artificial cycle. During the
      simulated luteal phase, all mucus scores were <=5 (median 3.5; range 1-5),
      similar to scores seen in the luteal phase of natural cycles (median 1; range 1
      3). CONCLUSIONS: Our artificial cycle model (leuprolide acetate suppression) and
      dose escalation with estradiol patches produced favourable cervical mucus with
      mucus scores similar to those in the periovulatory phase of natural menstrual
      cycles. Additional studies are needed to validate the model for evaluation of
      mucus effects of contraceptive agents.

PMID- 29457759
TI  - ?

PMID- 29457761
TI  - Degradation of anti-inflammatory drugs in municipal wastewater by heterogeneous
      photocatalysis and electro-Fenton process.
AB  - Non-steroidal anti-inflammatory drugs (NSAID) are compounds frequently found in
      municipal wastewater and their degradation by conventional wastewater treatment
      plants (WWTP) is generally incomplete. This study compared the efficiency of two
      advanced oxidation processes (AOP), namely heterogeneous photocatalysis (HP) and
      electro-Fenton (EF), in the degradation of a mixture of common NSAID (diclofenac,
      ibuprofen and naproxen) dissolved in either deionized water or effluent from a
      WWTP. Both processes were effective in degrading the NSAID mixture and the trend
      of degradation was as follows, diclofenac > naproxen > ibuprofen. EF with a
      current density of 40 mA cm-2 and 0.3 mmol Fe2+ L-1 was the most efficient
      process to mineralize the organic compounds, achieving up to 92% TOC removal in
      deionized water and 90% in the WWTP effluent after 3 h of reaction. HP with 1.4 g
      TiO2 L-1 at pH 7 under sunlight, produced 85% TOC removal in deionized water and
      39% in WWTP effluent also after 3 h treatment. The lower TOC removal efficiency
      shown by HP with the WWTP effluent was attributed mainly to the scavenging of
      reactive species by background organic matter in the wastewater. On the contrary,
      inorganic ions in the wastewater may produce oxidazing species during the EF
      process, which contributes to a higher degradation efficiency. EF is a promising
      option for the treatment of anti-inflammatory pharmaceuticals in municipal WWTP
      at competitive electrical energy efficiencies.

PMID- 29457760
TI  - A systematic review of serious games in medical education: quality of evidence
      and pedagogical strategy.
AB  - INTRODUCTION: The literature shows an optimistic landscape for the effectiveness
      of games in medical education. Nevertheless, games are not considered mainstream
      material in medical teaching. Two research questions that arise are the
      following: What pedagogical strategies do developers use when creating games for
      medical education? And what is the quality of the evidence on the effectiveness
      of games? METHODS: A systematic review was made by a multi-disciplinary team of
      researchers following the Cochrane Collaboration Guidelines. We included peer
      reviewed journal articles which described or assessed the use of serious games or
      gamified apps in medical education. We used the Medical Education Research Study
      Quality Instrument (MERSQI) to assess the quality of evidence in the use of
      games. We also evaluated the pedagogical perspectives of such articles. RESULTS:
      Even though game developers claim that games are useful pedagogical tools, the
      evidence on their effectiveness is moderate, as assessed by the MERSQI score.
      Behaviourism and cognitivism continue to be the predominant pedagogical
      strategies, and games are complementary devices that do not replace traditional
      medical teaching tools. Medical educators prefer simulations and quizzes focused
      on knowledge retention and skill development through repetition and do not demand
      the use of sophisticated games in their classrooms. Moreover, public access to
      medical games is limited. DISCUSSION: Our aim was to put the pedagogical strategy
      into dialogue with the evidence on the effectiveness of the use of medical games.
      This makes sense since the practical use of games depends on the quality of the
      evidence about their effectiveness. Moreover, recognition of said pedagogical
      strategy would allow game developers to design more robust games which would
      greatly contribute to the learning process.

PMID- 29457762
TI  - Editorial: Herbal Medicine on High Impact Disease: The Current Progress and
      Application.

PMID- 29457763
TI  - Editorial: Analytical Advances in Clinical and Forensic Toxicology.

PMID- 29457764
TI  - Everybody Knows Somebody.
AB  - Over the course of the last two decades, much progress has been made in the
      approaches to the care of people with mental health and addiction challenges. Yet
      there is still more work to do in terms of advocacy and the provision of
      meaningful and effective support for these individuals.

PMID- 29457765
TI  - Nursing Leadership: Making a Difference in Mental Health and Addictions.
AB  - Five nurse leaders in mental health offer their perspectives on key issues facing
      the sector and reflect on how nurses can make a difference in the following
      critical areas: nursing practice, transitions of care, innovative technologies,
      challenging stigma and creating patient partnerships.

PMID- 29457766
TI  - Addressing Gaps in Mental Health and Addictions Nursing Leadership: An Innovative
      Professional Development Initiative.
AB  - Mental health and addictions services are integral to Canada's healthcare system,
      and yet it is difficult to recruit experienced nurse leaders with advanced
      practice, management or clinical informatics expertise in this field. Master's
      level graduates, aspiring to be mental health nurse leaders, often lack the
      confidence and experience required to lead quality improvement, advancements in
      clinical care, service design and technology innovations for improved patient
      care. This paper describes an initiative that develops nursing leaders through a
      unique scholarship, internship and mentorship model, which aims to foster
      confidence, critical thinking and leadership competency development in the mental
      health and addictions context. The "Mutual Benefits Model" framework was applied
      in the design and evaluation of the initiative. It outlines how mentee, mentor
      and organizational needs can drive strategic planning of resource investment,
      mentorship networks and relevant leadership competency-based learning plans to
      optimize outcomes. Five-year individual and organizational outcomes are
      described.

PMID- 29457767
TI  - Starting at the Beginning: The Role of Public Health Nursing in Promoting Infant
      and Early Childhood Mental Health.
AB  - The promotion, protection and restoration of mental health are foundational to
      healthy communities. However, most mental health services in Canada, already
      underfunded in comparison to hospital-based medical-surgical programs, continue
      to be focused on providing reactive acute care. Mental health problems in later
      life often have their roots in the prenatal, infancy and early childhood life
      periods, and considerable evidence has accumulated about the effectiveness of
      interventions during this period of time. Although public health nurses (PHNs)
      play a leadership role in Canada in developing and providing programs that
      promote mental health in the early years, much of this work is largely invisible.
      This paper describes the concept of infant and early childhood mental health,
      identifies key national policies, and explores the role of PHNs in supporting
      mental wellness for infants and families, in keeping with health equity and
      Indigenous perspectives. Canadian practice exemplars are provided to highlight
      the value of investing in the promotion of infant and early childhood mental
      health.

PMID- 29457768
TI  - Mending the Cracks: A Case Study in Using Technology to assist with Transitional
      Care for Persons with Dementia.
AB  - Transitions between hospital and community are particularly challenging for
      vulnerable adults experiencing behavioural and psychological symptoms (BPSD) of
      dementia. Too often, miscommunication results in triggering a recurrence of
      disruptive behaviours leading to frustration of staff and families. As part of
      the implementation of Health Quality Ontario (HQO) Quality Standards, this
      project involved improving transitions using an electronic-based care plan on a
      23-bed geriatric dementia unit in a mental health hospital. "My Dementia
      Careplan," is an interprofessional care plan that was developed in the electronic
      medical record (EMR) to enhance communication of information between healthcare
      providers when patients are being discharged to the community. It is written from
      the patient's perspective in collaboration with the family and interprofessional
      team. It describes strategies to manage behavioural challenges along with the
      standardized tools to objectively monitor progress. This care planning will help
      to support transition of knowledge between hospital and community.

PMID- 29457769
TI  - Digital Mental Health - Innovations in Consumer Driven Care.
AB  - Barriers such as stigma and access issues prevent 60% of Canadians with mental
      health issues from seeking help. Saint Elizabeth Health Care's IntelligentCareTM
      Platform supports a range of digital health solutions for holistic health
      including three specific innovations: a secure social networking tool, an
      artificial intelligence-driven assistant that uses conversational cognitive
      behaviour therapy techniques, and a mobile mindfulness meditation application
      that generates personalized meditation suggestions. People use these self-help
      tools to cope with their mental health challenges. Healthcare providers are
      encouraged to explore the benefits and drawbacks of digital solutions for mental
      health, and consider the new skills, ethical implications and research
      opportunities that are needed when supporting patients who use these digital
      tools.

PMID- 29457770
TI  - Lessons Learned After Losing my Brother to an Overdose: A Call to Action for
      Nurse Leaders.
AB  - The current overdose epidemic we are facing in Canada and internationally calls
      on nursing leaders to prioritize holistic and compassionate care for people who
      use drugs (PWUD) and their families. Nurses are well positioned to provide person
      centred care and advocate with and for this population. To do so requires an
      examination of one's personal values and beliefs surrounding drugs and the people
      who use them. As a nurse leader, I was forced to confront my views about illicit
      drug use following the untimely death of my brother Brad from overdose. This
      paper chronicles my personal experience with his death and subsequent journey
      into advocacy for drug policy reform amidst an emerging overdose crisis. This
      short paper is written from my personal perspective, and informed by both
      personal and professional experiences in drug policy reform. It addresses
      strategies for challenging stigma and opportunities for partnering with PWUD
      through engagement in harm reduction.

PMID- 29457771
TI  - Nurses Taking the Lead: A Community Engagement and Knowledge Exchange Forum on
      Substance Abuse and Addiction in Prince Albert, Saskatchewan.
AB  - Prince Albert, Saskatchewan, is experiencing a substance use and addiction crisis
      with devastating consequences. To engage local stakeholders on substance use and
      addiction issues, nurse researchers at the University of Saskatchewan, Prince
      Albert Campus, planned and organized a one-day community engagement and knowledge
      exchange forum. The forum provided the opportunity for interested community
      groups, members and individuals to share their experiences and to explore novel
      ways to prevent and respond to the substance abuse and addiction challenges in
      the region. Participants included community leaders, people and families living
      with addiction, service providers, local stakeholders, health professionals,
      researchers and Indigenous Elders. This paper describes the process and outcomes
      of this event and describes the role of nurse scholars in leading these efforts.

PMID- 29457772
TI  - Patient Partnership: One Organization's Journey.
AB  - Patient partnership has become a central element of healthcare delivery in many
      countries. The concept has specific relevance in mental health, as it is a
      critical enabler of recovery and healing (Bailey and Williams 2014). Patient
      partnership implies active engagement of patients in shaping decisions at the
      direct care, organizational and system level (Health Quality Ontario 2017). This
      article will outline the concept of patient partnership, and highlight the
      journey of one mental health.

PMID- 29457773
TI  - Optical waveguide and room temperature high-quality nanolasers from tin-catalyzed
      CdSSe nanostructures.
AB  - A simple two-step CVD method is developed to realize the growth of high-quality
      tin-catalyzed CdSSe alloy nanowires. Microstructural characterizations
      demonstrate that these wires are high-quality crystalline nanostructures. Local
      photoluminescence investigation of these nanostructures shows a typical band edge
      emission at 656 nm with a full-width at half-maximum of 22.3 nm. Optical
      waveguide measurement along an individual nanowire indicates that the output
      signal of the guided light has a rapid linear decrease accompanied with maximum
      red-shift about 109 meV after the transmission of 102 MUm. This obvious red-shift
      is caused by the intensive band-tail absorption during the optical transmission
      process. Moreover, optically pumped nanolasers are successfully realized at room
      temperature based on these unique wires, further demonstrating the achievement of
      stimulated emission from spontaneous emission, promoted by the pump power
      intensity. This work may find a simple route to the manufacture of superior
      nanowires for applications in waveguide and integrated photonic devices.

PMID- 29457774
TI  - A review of advances in pixel detectors for experiments with high rate and
      radiation.
AB  - The large Hadron collider (LHC) experiments ATLAS and CMS have established hybrid
      pixel detectors as the instrument of choice for particle tracking and vertexing
      in high rate and radiation environments, as they operate close to the LHC
      interaction points. With the high luminosity-LHC upgrade now in sight, for which
      the tracking detectors will be completely replaced, new generations of pixel
      detectors are being devised. They have to address enormous challenges in terms of
      data throughput and radiation levels, ionizing and non-ionizing, that harm the
      sensing and readout parts of pixel detectors alike. Advances in microelectronics
      and microprocessing technologies now enable large scale detector designs with
      unprecedented performance in measurement precision (space and time), radiation
      hard sensors and readout chips, hybridization techniques, lightweight supports,
      and fully monolithic approaches to meet these challenges. This paper reviews the
      world-wide effort on these developments.

PMID- 29457775
TI  - Mechanical properties of hollow and water-filled graphyne nanotube and carbon
      nanotube hybrid structure.
AB  - By performing molecular dynamics simulations, a GNT/CNT hybrid structure
      constructed via combing (6, 6) graphyne nanotube (GNT) with (6, 6) carbon
      nanotube (CNT) has been designed and investigated. The mechanical properties
      induced by the percentage of GNT, water content and electric field were examined.
      Calculation results reveal that the fracture strain and strength of hollow hybrid
      structure are remarkably smaller than that of perfect (6, 6) CNT. In addition,
      the Young's modulus decreases monotonously with the increase of percentage of
      GNT. More importantly, the tunable mechanical properties of hybrid structure can
      be achieved through filling with water molecules and applying an electric field
      along tensile direction. Specifically, increasing water content from 0.0 to 8.70
      mmol g-1 in the absence of electric field could result in fracture strain and
      strength reducing by 15.09% and 12.87%, respectively. Besides, enhancing fracture
      strain and strength of water-filled hybrid structure with water content of 8.70
      mmol g-1 can also be obtained with rising electric field intensity. These
      findings would provide a valuable theoretical basis for designing and fabricating
      a nanodevice with controllable mechanical performances.

PMID- 29457776
TI  - Free-anchored Nb2O5@graphene networks for ultrafast-stable lithium storage.
AB  - Orthorhombic Nb2O5 (T-Nb2O5) has structural merit but poor electrical
      conductivity, limiting their applications in energy storage. Although graphene is
      frequently adopted to effectively improve its electrochemical properties, the
      ordinary modified methods cannot meet the growing demands for high-performance.
      Here, we demonstrate that different graphene modified routes play a vital role in
      affecting the electrochemical performances of T-Nb2O5. By only manual shaking
      within one minute, Nb2O5 nano-particles can be rapidly adsorbed onto graphene,
      then the free-anchored T-Nb2O5@graphene three-dimensional networks can be
      successfully prepared based on hydrogel method. As for the application in lithium
      ion batteries, it performs outstanding rate character (129 mA h g-1 (25C rate),
      110 mA h g-1 (50C rate) and 90 mA h g-1 (100C rate), correspond to 79%, 67% and
      55% capacity of 0.5C rate, respectively) and excellent long-term cycling feature
      (~70% capacity retention after 20000 cycles). Moreover, it still maintains
      similar ultrafast-stable lithium storage performances when Cu foil is substituted
      by Al foil as current collector. In addition, relevant kinetics mechanisms are
      also expounded. This work provides a versatile strategy for the preparation of
      graphene modified Nb2O5 or other types of nanoparticles.

PMID- 29457777
TI  - Perfect-absorption graphene metamaterials for surface-enhanced molecular
      fingerprint spectroscopy.
AB  - Graphene plasmon with extremely strong light confinement and tunable resonance
      frequency represents a promising surface-enhanced infrared absorption (SEIRA)
      sensing platform. However, plasmonic absorption is relatively weak (approximately
      1%-9%) in monolayer graphene nanostructures, which would limit its sensitivity.
      Here, we theoretically propose a hybrid plasmon-metamaterial structure that can
      realize perfect absorption in graphene with a low carrier mobility of 1000 cm2 V
      1 s-1. This structure combines a gold reflector and a gold grating to the
      graphene plasmon structures, which introduce interference effect and the
      lightning-rod effect, respectively, and largely enhance the coupling of light to
      graphene. The vibration signal of trace molecules can be enhanced up to 2000-fold
      at the hotspot of the perfect-absorption structure, enabling the SEIRA sensing to
      reach the molecular level. This hybrid metal-graphene structure provides a novel
      path to generate high sensitivity in nanoscale molecular recognition for numerous
      applications.

PMID- 29457778
TI  - Theoretical investigation of performance of armchair graphene nanoribbon field
      effect transistors.
AB  - In this paper, we theoretically investigate the highest possible expected
      performance for graphene nanoribbon field effect transistors (GNRFETs) for a wide
      range of operation voltages and device structure parameters, such as the width of
      the graphene nanoribbon and gate length. We formulated a self-consistent, non
      equilibrium Green's function method in conjunction with the Poisson equation and
      modeled the operation of nanometer sized GNRFETs, of which GNR channels have
      finite bandgaps so that the GNRFET can operate as a switch. We propose a metric
      for competing with the current silicon CMOS high performance or low power devices
      and explain that this can vary greatly depending on the GNRFET structure
      parameters.

PMID- 29457779
TI  - Embedding ultrafine ZnSnO3 nanoparticles into reduced graphene oxide composites
      as high-performance electrodes for lithium ion batteries.
AB  - Ultrafine ZnSnO3 nanoparticles, with an average diameter of 45 nm, homogeneously
      grown on reduced graphene oxide (rGO) have been successfully fabricated via
      methods of low temperature coprecipitation, colloid electrostatic self-assembly,
      and hydrothermal treatment. The uniformly distributed ZnSnO3 nanocrystals could
      inhibit the restacking of rGO sheets. In turn, the existence of rGO could hinder
      the growth and aggregation of ZnSnO3 nanoparticles in the synthesis process,
      increase the conductivity of the composite, and buffer the volume expansion of
      the ZnSnO3 nanocrystals upon lithium ion insertion and extraction. The obtained
      ZnSnO3/rGO exhibited superior cycling stability with a discharge/charge capacity
      of 718/696 mA h g-1 after 100 cycles at a current density of 0.1 A g-1.

PMID- 29457780
TI  - Comment on 'Nanoscale mapping of optical band gaps using monochromated electron
      energy loss spectroscopy'.

PMID- 29457781
TI  - Efficient synthesis of tungsten oxide hydrate-based nanocomposites for
      applications in bifunctional electrochromic-energy storage devices.
AB  - In this work, we realized the large-scale synthesis of WO3 . H2O nanoflakes
      (NFs), g-C3N4/WO3 . H2O nanocomposite (NC) and graphene (G)/WO3 . H2O NC via a
      sonochemical process with tungsten salt as the precursor, g-C3N4 or G sheets as
      the supports, and distilled water as the solvent. Both the g-C3N4/WO3 . H2O NC
      and G/WO3 . H2O NC exhibited much better electrochromic (EC) performance (higher
      coloration efficiencies and faster response times) than that of the WO3 . H2O
      NFs. Using the WO3 . H2O-based materials as electrode materials, EC batteries
      that integrate the energy storage and EC functions in one device have been
      assembled. The energy status of the EC batteries could be visually indicated by
      the reversible color variations. Compared with the plain WO3 . H2O-based EC
      batteries, the NC-based EC batteries possessed a lower color contrast between the
      charged and discharged conditions but much longer discharge durations. The EC
      batteries could be quickly charged in a few seconds by adding H2O2, and the
      charged batteries exhibited significantly-enhanced discharging durations in
      comparison with the initial ones. The g-C3N4/WO3 . H2O NC-EC batteries charged by
      a small amount of H2O2 could produce a long discharging duration up to 760 min.

PMID- 29457782
TI  - Hypothalamic ER-associated degradation regulates POMC maturation, feeding, and
      age-associated obesity.
AB  - Pro-opiomelanocortin (POMC) neurons function as key regulators of metabolism and
      physiology by releasing prohormone-derived neuropeptides with distinct biological
      activities. However, our understanding of early events in prohormone maturation
      in the ER remains incomplete. Highlighting the significance of this gap in
      knowledge, a single POMC cysteine-to-phenylalanine mutation at position 28 (POMC
      C28F) is defective for ER processing and causes early onset obesity in a dominant
      negative manner in humans through an unclear mechanism. Here, we report a
      pathologically important role of Sel1L-Hrd1, the protein complex of ER-associated
      degradation (ERAD), within POMC neurons. Mice with POMC neuron-specific Sel1L
      deficiency developed age-associated obesity due, at least in part, to the ER
      retention of POMC that led to hyperphagia. The Sel1L-Hrd1 complex targets a
      fraction of nascent POMC molecules for ubiquitination and proteasomal
      degradation, preventing accumulation of misfolded and aggregated POMC, thereby
      ensuring that another fraction of POMC can undergo normal posttranslational
      processing and trafficking for secretion. Moreover, we found that the disease
      associated POMC-C28F mutant evades ERAD and becomes aggregated due to the
      presence of a highly reactive unpaired cysteine thiol at position 50. Thus, this
      study not only identifies ERAD as an important mechanism regulating POMC
      maturation within the ER, but also provides insights into the pathogenesis of
      monogenic obesity associated with defective prohormone folding.

PMID- 29457783
TI  - Cellular senescence in brain aging and neurodegenerative diseases: evidence and
      perspectives.
AB  - Along with a general decline in overall health, most chronic degenerative human
      diseases are inherently associated with increasing age. Age-associated cognitive
      impairments and neurodegenerative diseases, such as Parkinson's and Alzheimer's
      diseases, are potentially debilitating conditions that lack viable options for
      treatment, resulting in a tremendous economic and societal cost. Most high
      profile clinical trials for neurodegenerative diseases have led to inefficacious
      results, suggesting that novel approaches to treating these pathologies are
      needed. Numerous recent studies have demonstrated that senescent cells, which are
      characterized by sustained cell cycle arrest and production of a distinct
      senescence-associated secretory phenotype, accumulate with age and at sites of
      age-related diseases throughout the body, where they actively promote tissue
      deterioration. Cells with features of senescence have been detected in the
      context of brain aging and neurodegenerative disease, suggesting that they may
      also promote dysfunction. Here, we discuss the evidence implicating senescent
      cells in neurodegenerative diseases, the mechanistic contribution of these cells
      that may actively drive neurodegeneration, and how these cells or their effects
      may be targeted therapeutically.

PMID- 29457784
TI  - HIV latency is reversed by ACSS2-driven histone crotonylation.
AB  - Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency
      is epigenetically regulated. While the effects of histone acetylation and
      methylation at the HIV long-terminal repeat (LTR) have been described, our
      knowledge of the proviral epigenetic landscape is incomplete. We report that a
      previously unrecognized epigenetic modification of the HIV LTR, histone
      crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was
      achieved following the induction of histone crotonylation through increased
      expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain
      family member 2 (ACSS2). This reprogrammed the local chromatin at the HIV LTR
      through increased histone acetylation and reduced histone methylation.
      Pharmacologic inhibition or siRNA knockdown of ACSS2 diminished histone
      crotonylation-induced HIV replication and reactivation. ACSS2 induction was
      highly synergistic in combination with either a protein kinase C agonist (PEP005)
      or a histone deacetylase inhibitor (vorinostat) in reactivating latent HIV. In
      the SIV-infected nonhuman primate model of AIDS, the expression of ACSS2 was
      significantly induced in intestinal mucosa in vivo, which correlated with altered
      fatty acid metabolism. Our study links the HIV/SIV infection-induced fatty acid
      enzyme ACSS2 to HIV latency and identifies histone lysine crotonylation as a
      novel epigenetic regulator for HIV transcription that can be targeted for HIV
      eradication.

PMID- 29457785
TI  - TIA1 variant drives myodegeneration in multisystem proteinopathy with SQSTM1
      mutations.
AB  - Multisystem proteinopathy (MSP) involves disturbances of stress granule (SG)
      dynamics and autophagic protein degradation that underlie the pathogenesis of a
      spectrum of degenerative diseases that affect muscle, brain, and bone.
      Specifically, identical mutations in the autophagic adaptor SQSTM1 can cause
      varied penetrance of 4 distinct phenotypes: amyotrophic lateral sclerosis (ALS),
      frontotemporal dementia, Paget's disease of the bone, and distal myopathy. It has
      been hypothesized that clinical pleiotropy relates to additional genetic
      determinants, but thus far, evidence has been lacking. Here, we provide evidence
      that a TIA1 (p.N357S) variant dictates a myodegenerative phenotype when
      inherited, along with a pathogenic SQSTM1 mutation. Experimentally, the TIA1
      N357S variant significantly enhances liquid-liquid-phase separation in vitro and
      impairs SG dynamics in living cells. Depletion of SQSTM1 or the introduction of a
      mutant version of SQSTM1 similarly impairs SG dynamics. TIA1-N357S-persistent SGs
      have increased association with SQSTM1, accumulation of ubiquitin conjugates, and
      additional aggregated proteins. Synergistic expression of the TIA1-N357S variant
      and a SQSTM1-A390X mutation in myoblasts leads to impaired SG clearance and
      myotoxicity relative to control myoblasts. These findings demonstrate a
      pathogenic connection between SG homeostasis and ubiquitin-mediated autophagic
      degradation that drives the penetrance of an MSP phenotype.

PMID- 29457787
TI  - Alternative macrophages in atherosclerosis: not always protective!
AB  - Atherosclerosis is a chronic inflammatory disease of the vasculature that is
      initiated by cholesterol deposition into the arterial wall, which triggers the
      infiltration of immune and inflammatory cells, including monocytes and
      macrophages. As atherosclerotic plaques progress, localized hypoxia promotes
      compensatory angiogenesis from the vasa vasorum. Immature neovessels are prone to
      leakage, thus destabilizing the plaque and leading to intraplaque hemorrhage.
      Macrophages with different phenotypes, ranging from classical inflammatory
      subtypes to alternatively activated antiinflammatory macrophages, have been
      identified in atherosclerotic lesions. Antiinflammatory hemoglobin-scavenging
      CD163+ macrophages are present in neovessel- and hemorrhage-rich areas; however,
      the role of these macrophages in atherogenesis has been unclear. In this issue of
      the JCI, Guo, Akahori, and colleagues show that CD163+ macrophages promote
      angiogenesis, vessel permeability, and leucocyte infiltration in human and mouse
      atherosclerotic lesions through a mechanism involving
      hemoglobin:haptoglobin/CD163/HIF1alpha-mediated VEGF induction. This study thus
      identifies proatherogenic properties of CD163+ macrophages, which previously were
      thought to be beneficial.

PMID- 29457786
TI  - Intracellular lipid metabolism impairs beta cell compensation during diet-induced
      obesity.
AB  - The compensatory proliferation of insulin-producing beta cells is critical to
      maintaining glucose homeostasis at the early stage of type 2 diabetes. Failure of
      beta cells to proliferate results in hyperglycemia and insulin dependence in
      patients. To understand the effect of the interplay between beta cell
      compensation and lipid metabolism upon obesity and peripheral insulin resistance,
      we eliminated LDL receptor-related protein 1 (LRP1), a pleiotropic mediator of
      cholesterol, insulin, energy metabolism, and other cellular processes, in beta
      cells. Upon high-fat diet exposure, LRP1 ablation significantly impaired insulin
      secretion and proliferation of beta cells. The diminished insulin signaling was
      partly contributed to by the hypersensitivity to glucose-induced, Ca2+-dependent
      activation of Erk and the mTORC1 effector p85 S6K1. Surprisingly, in LRP1
      deficient islets, lipotoxic sphingolipids were mitigated by improved lipid
      metabolism, mediated at least in part by the master transcriptional regulator
      PPARgamma2. Acute overexpression of PPARgamma2 in beta cells impaired insulin
      signaling and insulin secretion. Elimination of Apbb2, a functional regulator of
      LRP1 cytoplasmic domain, also impaired beta cell function in a similar fashion.
      In summary, our results uncover the double-edged effects of intracellular lipid
      metabolism on beta cell function and viability in obesity and type 2 diabetes and
      highlight LRP1 as an essential regulator of these processes.

PMID- 29457788
TI  - SCN5A: the greatest HITS collection.
AB  - Heart failure (HF) has been referred to as the cardiovascular epidemic of our
      time. Understanding the molecular determinants of HF disease progression and
      mortality risk is of utmost importance. In this issue of the JCI, Zhang et al.
      uncover an important link between clinical HF mortality risk and a common variant
      that regulates SCN5A expression through microRNA-dependent (miR
      dependent)mechanisms. They also demonstrate that haploinsufficiency of SCN5A is
      associated with increased accumulation of reactive oxygen species (ROS) in a
      genetically engineered murine model. Their data suggest that even modest
      depression of SCN5A expression may promote pathologic cardiac remodeling and
      progression of HF.

PMID- 29457789
TI  - A common variant alters SCN5A-miR-24 interaction and associates with heart
      failure mortality.
AB  - SCN5A encodes the voltage-gated Na+ channel NaV1.5 that is responsible for
      depolarization of the cardiac action potential and rapid intercellular
      conduction. Mutations disrupting the SCN5A coding sequence cause inherited
      arrhythmias and cardiomyopathy, and single-nucleotide polymorphisms (SNPs) linked
      to SCN5A splicing, localization, and function associate with heart failure
      related sudden cardiac death. However, the clinical relevance of SNPs that
      modulate SCN5A expression levels remains understudied. We recently generated a
      transcriptome-wide map of microRNA (miR) binding sites in human heart, evaluated
      their overlap with common SNPs, and identified a synonymous SNP (rs1805126)
      adjacent to a miR-24 site within the SCN5A coding sequence. This SNP was
      previously shown to reproducibly associate with cardiac electrophysiological
      parameters, but was not considered to be causal. Here, we show that miR-24
      potently suppresses SCN5A expression and that rs1805126 modulates this
      regulation. We found that the rs1805126 minor allele associates with decreased
      cardiac SCN5A expression and that heart failure subjects homozygous for the minor
      allele have decreased ejection fraction and increased mortality, but not
      increased ventricular tachyarrhythmias. In mice, we identified a potential basis
      for this in discovering that decreased Scn5a expression leads to accumulation of
      myocardial reactive oxygen species. Together, these data reiterate the importance
      of considering the mechanistic significance of synonymous SNPs as they relate to
      miRs and disease, and highlight a surprising link between SCN5A expression and
      nonarrhythmic death in heart failure.

PMID- 29457791
TI  - Quantitative mapping and minimization of super-resolution optical imaging
      artifacts.
AB  - Super-resolution microscopy depends on steps that can contribute to the formation
      of image artifacts, leading to misinterpretation of biological information. We
      present NanoJ-SQUIRREL, an ImageJ-based analytical approach that provides
      quantitative assessment of super-resolution image quality. By comparing
      diffraction-limited images and super-resolution equivalents of the same
      acquisition volume, this approach generates a quantitative map of super
      resolution defects and can guide researchers in optimizing imaging parameters.

PMID- 29457792
TI  - On the design of CRISPR-based single-cell molecular screens.
AB  - Several groups recently coupled CRISPR perturbations and single-cell RNA-seq for
      pooled genetic screens. We demonstrate that vector designs of these studies are
      susceptible to ~50% swapping of guide RNA-barcode associations because of
      lentiviral template switching. We optimized a published alternative, CROP-seq, in
      which the guide RNA also serves as the barcode, and here confirm that this
      strategy performs robustly and doubled the rate at which guides are assigned to
      cells to 94%.

PMID- 29457790
TI  - CD163+ macrophages promote angiogenesis and vascular permeability accompanied by
      inflammation in atherosclerosis.
AB  - Intake of hemoglobin by the hemoglobin-haptoglobin receptor CD163 leads to a
      distinct alternative non-foam cell antiinflammatory macrophage phenotype that was
      previously considered atheroprotective. Here, we reveal an unexpected but
      important pathogenic role for these macrophages in atherosclerosis. Using human
      atherosclerotic samples, cultured cells, and a mouse model of advanced
      atherosclerosis, we investigated the role of intraplaque hemorrhage on macrophage
      function with respect to angiogenesis, vascular permeability, inflammation, and
      plaque progression. In human atherosclerotic lesions, CD163+ macrophages were
      associated with plaque progression, microvascularity, and a high level of
      HIF1alpha and VEGF-A expression. We observed irregular vascular endothelial
      cadherin in intraplaque microvessels surrounded by CD163+ macrophages. Within
      these cells, activation of HIF1alpha via inhibition of prolyl hydroxylases
      promoted VEGF-mediated increases in intraplaque angiogenesis, vascular
      permeability, and inflammatory cell recruitment. CD163+ macrophages increased
      intraplaque endothelial VCAM expression and plaque inflammation. Subjects with
      homozygous minor alleles of the SNP rs7136716 had elevated microvessel density,
      increased expression of CD163 in ruptured coronary plaques, and a higher risk of
      myocardial infarction and coronary heart disease in population cohorts. Thus, our
      findings highlight a nonlipid-driven mechanism by which alternative macrophages
      promote plaque angiogenesis, leakiness, inflammation, and progression via the
      CD163/HIF1alpha/VEGF-A pathway.

PMID- 29457793
TI  - Identifying the favored mutation in a positive selective sweep.
AB  - Most approaches that capture signatures of selective sweeps in population
      genomics data do not identify the specific mutation favored by selection. We
      present iSAFE (for "integrated selection of allele favored by evolution"), a
      method that enables researchers to accurately pinpoint the favored mutation in a
      large region (~5 Mbp) by using a statistic derived solely from population
      genetics signals. iSAFE does not require knowledge of demography, the phenotype
      under selection, or functional annotations of mutations.

PMID- 29457794
TI  - Recon3D enables a three-dimensional view of gene variation in human metabolism.
AB  - Genome-scale network reconstructions have helped uncover the molecular basis of
      metabolism. Here we present Recon3D, a computational resource that includes three
      dimensional (3D) metabolite and protein structure data and enables integrated
      analyses of metabolic functions in humans. We use Recon3D to functionally
      characterize mutations associated with disease, and identify metabolic response
      signatures that are caused by exposure to certain drugs. Recon3D represents the
      most comprehensive human metabolic network model to date, accounting for 3,288
      open reading frames (representing 17% of functionally annotated human genes),
      13,543 metabolic reactions involving 4,140 unique metabolites, and 12,890 protein
      structures. These data provide a unique resource for investigating molecular
      mechanisms of human metabolism. Recon3D is available at http://vmh.life.

PMID- 29457795
TI  - Random access in large-scale DNA data storage.
AB  - Synthetic DNA is durable and can encode digital data with high density, making it
      an attractive medium for data storage. However, recovering stored data on a large
      scale currently requires all the DNA in a pool to be sequenced, even if only a
      subset of the information needs to be extracted. Here, we encode and store 35
      distinct files (over 200 MB of data), in more than 13 million DNA
      oligonucleotides, and show that we can recover each file individually and with no
      errors, using a random access approach. We design and validate a large library of
      primers that enable individual recovery of all files stored within the DNA. We
      also develop an algorithm that greatly reduces the sequencing read coverage
      required for error-free decoding by maximizing information from all sequence
      reads. These advances demonstrate a viable, large-scale system for DNA data
      storage and retrieval.

PMID- 29457797
TI  - The Application and Usefulness of Economic Analyses for Water Quality Management
      in Coastal Areas.

PMID- 29457796
TI  - H3B-8800, an orally available small-molecule splicing modulator, induces
      lethality in spliceosome-mutant cancers.
AB  - Genomic analyses of cancer have identified recurrent point mutations in the RNA
      splicing factor-encoding genes SF3B1, U2AF1, and SRSF2 that confer an alteration
      of function. Cancer cells bearing these mutations are preferentially dependent on
      wild-type (WT) spliceosome function, but clinically relevant means to
      therapeutically target the spliceosome do not currently exist. Here we describe
      an orally available modulator of the SF3b complex, H3B-8800, which potently and
      preferentially kills spliceosome-mutant epithelial and hematologic tumor cells.
      These killing effects of H3B-8800 are due to its direct interaction with the SF3b
      complex, as evidenced by loss of H3B-8800 activity in drug-resistant cells
      bearing mutations in genes encoding SF3b components. Although H3B-8800 modulates
      WT and mutant spliceosome activity, the preferential killing of spliceosome
      mutant cells is due to retention of short, GC-rich introns, which are enriched
      for genes encoding spliceosome components. These data demonstrate the therapeutic
      potential of splicing modulation in spliceosome-mutant cancers.

PMID- 29457798
TI  - Erratum: Endoscopic Medical Devices for Primary Obesity Treatment in Patients
      With Diabetes. Diabetes Spectrum 2017;30;258-264 (DOI:10.2337/ds017-0046).
AB  - [This corrects the article on p. 258 in vol. 30, PMID: 29151716.].

PMID- 29457799
TI  - Erratum to: What incentives increase data sharing in health and medical research?
      A systematic review.
AB  - [This corrects the article DOI: 10.1186/s41073-017-0028-9.].

PMID- 29457800
TI  - Comment to: Focal segmental glomerulosclerosis associated with mitochondrial
      disease by Lim et al. in Clin Nephrol Case Stud. 2017; 5: 20-25.
AB  - Not available.

PMID- 29457801
TI  - Time Domain and Frequency Domain Deterministic Channel Modeling for Tunnel/Mining
      Environments.
AB  - Understanding wireless channels in complex mining environments is critical for
      designing optimized wireless systems operated in these environments. In this
      paper, we propose two physics-based, deterministic ultra-wideband (UWB) channel
      models for characterizing wireless channels in mining/tunnel environments - one
      in the time domain and the other in the frequency domain. For the time domain
      model, a general Channel Impulse Response (CIR) is derived and the result is
      expressed in the classic UWB tapped delay line model. The derived time domain
      channel model takes into account major propagation controlling factors including
      tunnel or entry dimensions, frequency, polarization, electrical properties of the
      four tunnel walls, and transmitter and receiver locations. For the frequency
      domain model, a complex channel transfer function is derived analytically. Based
      on the proposed physics-based deterministic channel models, channel parameters
      such as delay spread, multipath component number, and angular spread are
      analyzed. It is found that, despite the presence of heavy multipath, both channel
      delay spread and angular spread for tunnel environments are relatively smaller
      compared to that of typical indoor environments. The results and findings in this
      paper have application in the design and deployment of wireless systems in
      underground mining environments.

PMID- 29457802
TI  - Corrigendum: Stimulating the Right Temporoparietal Junction with tDCS Decreases
      Deception in Moral Hypocrisy and Unfairness.
AB  - [This corrects the article on p. 2033 in vol. 8, PMID: 29218025.].

PMID- 29457803
TI  - Temperature and Humidity Calibration of a Low-Cost Wireless Dust Sensor for Real
      Time Monitoring.
AB  - This paper introduces the design, calibration, and validation of a low-cost
      portable sensor for the real-time measurement of dust particles within the
      environment. The proposed design consists of low hardware cost and calibration
      based on temperature and humidity sensing to achieve accurate processing of
      airborne dust density. Using commercial particulate matter sensors, a highly
      accurate air quality monitoring sensor was designed and calibrated using real
      world variations in humidity and temperature for indoor and outdoor applications.
      Furthermore, to provide a low-cost secure solution for real-time data transfer
      and monitoring, an onboard Bluetooth module with AES data encryption protocol was
      implemented. The wireless sensor was tested against a Dylos DC1100 Pro Air
      Quality Monitor, as well as an Alphasense OPC-N2 optical air quality monitoring
      sensor for accuracy. The sensor was also tested for reliability by comparing the
      sensor to an exact copy of itself under indoor and outdoor conditions. It was
      found that accurate measurements under real-world humid and temperature varying
      and dynamically changing conditions were achievable using the proposed sensor
      when compared to the commercially available sensors. In addition to accurate and
      reliable sensing, this sensor was designed to be wearable and perform real-time
      data collection and transmission, making it easy to collect and analyze data for
      air quality monitoring and real-time feedback in remote health monitoring
      applications. Thus, the proposed device achieves high quality measurements at
      lower-cost solutions than commercially available wireless sensors for air
      quality.

PMID- 29457804
TI  - Erratum: Multidisciplinary Team-Based Obesity Treatment in Patients With
      Diabetes: Current Practices and the State of the Science. Diabetes Spectrum
      2017;30:244-249 (DOI: 10.2337/ds17-0045).
AB  - [This corrects the article on p. 244 in vol. 30, PMID: 29151714.].

PMID- 29457805
TI  - Urinary metabolomic study of the antagonistic effect of P. ginseng in rats with
      estrogen decline using ultra performance liquid chromatography coupled with
      quadrupole time-of-flight mass spectrometry.
AB  - Estrogens are biologically active steroid hormones mainly released from the ovary
      by ovarian secretion of estrogen into the circulating blood to regulate or
      function at the distal target. Estrogens play an important role in the central
      nervous system, cardiovascular system and immune system, especially for post
      menopausal women. Panax ginseng Mayer has been reported to relieve women's
      menopausal symptoms and affect estrogen activities. However, the mechanism of its
      estrogen regulation has not yet been clearly investigated. In this work,
      ovariectomized rats were administered a P. ginseng decoction intragastrically for
      8 weeks. Urine samples were analyzed by ultra performance liquid chromatography
      coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to
      identify metabolites. The estrous cycle, body weight, uterine weight index and
      serum hormone levels were measured. The results showed that P. ginseng
      significantly prolonged the estrus stage, decreased the body weight and serum
      luteinizing hormone (LH) levels and increased the uterine weight index and serum
      estradiol (E2) levels of ovariectomized rats. A total of twelve potential
      biomarkers for which levels changed markedly upon treatment have been identified
      based on metabolomics. A systematic network analysis of their corresponding
      pathways indicates that the antagonistic effect of P. ginseng on ovariectomized
      rats occurs mainly through regulating steroid hormone metabolism, fatty acid
      biosynthesis, the citric acid cycle and tryptophan metabolism. In conclusion,
      this study validated the antagonistic effect of P. ginseng in rats with estrogen
      decline and explored the metabolic and biochemical mechanisms involved.

PMID- 29457806
TI  - Enhancement of the selectivity of MXenes (M2C, M = Ti, V, Nb, Mo) via oxygen
      functionalization: promising materials for gas-sensing and -separation.
AB  - Two-dimensional graphene-like materials, namely MXenes, have been proposed as
      potential materials for various applications. In this work, the reactivity and
      selectivity of four MXenes (i.e. M2C (M = Ti, V, Nb, Mo)) and their oxygen
      functionalized forms (i.e. O-MXenes or M2CO2) toward gas molecules were
      investigated by using the plane wave-based Density Functional Theory (DFT)
      calculations. Small gas molecules, which are commonly found in flue gas streams,
      are considered herein. Our results demonstrated that MXenes are very reactive.
      Chemisorption is a predominant process for gas adsorption on MXenes.
      Simultaneously dissociative adsorption can be observed in most cases. The high
      reactivity of their non-functionalized surface is attractive for catalytic
      applications. In contrast, their reactivity is reduced, but the selectivity is
      improved upon oxygen functionalization. Mo2CO2 and V2CO2 present good selectivity
      toward NO molecules, while Nb2CO2 and Ti2CO2 show good selectivity toward NH3.
      The electronic charge properties explain the nature of the substrates and also
      interactions between them and the adsorbed gases. Our results indicated that O
      MXenes are potential materials for gas-separation/capture, -storage, -sensing,
      etc. Furthermore, their structural stability and SO2-tolerant nature are
      attractive properties for using them in a wide range of applications. Our finding
      provides good information to narrow down the choices of materials to be tested in
      future experimental work.

PMID- 29457807
TI  - Copper(i) and silver(i) complexes of 9,9-dimethyl-4,5-bis(di-tert
      butylphosphino)xanthene: photophysical properties and structural rigidity under
      pressure.
AB  - The heteroleptic complexes [Cu(tBu-xantphos)(bpy)][PF6] and [Ag(tBu
      xantphos)(bpy)][PF6], where tBu-xantphos = 9,9-dimethyl-4,5-bis(di-tert
      butylphosphino)xanthene and bpy = 2,2'-bipyridine have been synthesized and their
      photophysical properties investigated. Single crystal X-ray diffraction studies
      of the compounds under ambient and increased pressure are presented; increase in
      pressure results in little structural perturbation. For the copper(i) complexes,
      the effects of changing the N^N ligand from bpy to 6-methyl-2,2'-bipyridine (6
      Mebpy), 6-bromo-2,2'-bipyridine (6-Brbpy), and 4,4'-di(tert-butyl)-2,2'
      bipyridine (4,4'-tBu2bpy) were also investigated. Emissions from the copper(i)
      complexes are weak, both in solution and the solid state and this is attributed
      to vibrational quenching effects of the tert-butyl substituents of the tBu
      xantphos ligands.

PMID- 29457808
TI  - CdS nanosphere-decorated hollow polyhedral ZCO derived from a metal-organic
      framework (MOF) for effective photocatalytic water evolution.
AB  - Semiconductor nanostructures have received considerable attention in the field of
      photocatalytic hydrogen evolution. However, eco-friendly, high efficiency, and
      low-cost semiconductor materials are still desired. In consideration of this,
      herein, we design a new and economic noble-metal-free CdS/ZnxCo3-xO4 (CdS/ZCO)
      nanohybrid photocatalyst using a metal-organic framework (MOF) template, which is
      a framework structure composed of organic ligands and metal ion nodes with
      different numbers of connections. The as-prepared CdS/ZCO composites with a large
      specific surface area and porous hollow structure exhibit remarkable catalytic
      activity and high stability for hydrogen generation. The hydrogen evolution rate
      is about 3978.6 MUmol g-1 h-1 with lactic acid as the sacrificial agent when the
      optimized amount of CdS nanoparticles (30 wt%) is decorated on the ZCO frame, and
      the production efficiency of H2 for CdS/ZCO is 4 times higher than that for CdS
      nanospheres or CdS/Co3O4. The significantly enhanced photocatalytic activity of
      CdS/ZCO is attributed to the efficient charge separation and transfer between the
      phase boundary of CdS and ZCO. In addition, the composites exhibit better
      hydrogen production in lactic acid than in methanol, and the remarkable catalytic
      activity and high stability of the CdS/ZCO composites for hydrogen evolution
      indicate that MOF-based composite materials have potential application prospects
      in energy conversion.

PMID- 29457809
TI  - Domain size polydispersity effects on the structural and dynamical properties in
      lipid monolayers with phase coexistence.
AB  - In lipid monolayers with phase coexistence, domains of the liquid-condensed phase
      always present size polydispersity. However, very few theoretical works consider
      size distribution effects on the monolayer properties. Because of the difference
      in surface densities, domains have excess dipolar density with respect to the
      surrounding liquid expanded phase, originating a dipolar inter-domain
      interaction. This interaction depends on the domain area, and hence the presence
      of a domain size distribution is associated with interaction polydispersity.
      Inter-domain interactions are fundamental to understanding the structure and
      dynamics of the monolayer. For this reason, it is expected that polydispersity
      significantly alters monolayer properties. By means of Brownian dynamics
      simulations, we study the radial distribution function (RDF), the average mean
      square displacement and the average time-dependent self-diffusion coefficient,
      D(t), of lipid monolayers with normally distributed size domains. For this
      purpose, we vary the relevant system parameters, polydispersity and interaction
      strength, within a range of experimental interest. We also analyze the
      consequences of using a monodisperse model to determine the interaction strength
      from an experimental RDF. We find that polydispersity strongly affects the value
      of the interaction strength, which is greatly underestimated if polydispersity is
      not considered. However, within a certain range of parameters, the RDF obtained
      from a polydisperse model can be well approximated by that of a monodisperse
      model, by suitably fitting the interaction strength, even for 40%
      polydispersities. For small interaction strengths or small polydispersities, the
      polydisperse systems obtained from fitting the experimental RDF have an average
      mean square displacement and D(t) in good agreement with that of the monodisperse
      system.

PMID- 29457810
TI  - A computational study of the catalytic aerobic epoxidation of propylene over the
      coordinatively unsaturated metal-organic framework Fe3(btc)2: formation of
      propylene oxide and competing reactions.
AB  - The aerobic epoxidation of propylene over the metal-organic framework Fe3(btc)2
      (btc = 1,3,5-benzentricarboxylate) as catalyst has been investigated by means of
      density functional calculations. The mechanisms of the reaction towards propylene
      oxide, carbonylic products (acetone and propanal) and a pi-allyl radical were
      investigated to assess the efficiency of Fe3(btc)2 for the selective formation of
      propylene oxide. Propylene oxide and carbonylic products are formed on Fe3(btc)2
      by proceeding via propyleneoxy intermediates in the first step. Subsequently, the
      intermediates can then either be transformed to propylene oxide by way of ring
      closure of the intermediate or to the carbonylic compounds of propanal and
      acetone via 1,2-hydride shift. The results show that the formation of propylene
      oxide is favored over the formation of carbonylic products mainly due to the
      activation barriers being 2-3 times smaller. The activation barriers for the
      formation of the propyleneoxy intermediates on the Fe3(btc)2 catalyst for the
      first and second reaction cycle are also lower than the barriers obtained for the
      formation of the pi-allyl radical that acts as the precursor to combustion
      products. On the basis of these computational results, we therefore expect a high
      catalytic selectivity of the Fe3(btc)2 catalyst with respect to the formation of
      propylene oxide. We also compared the catalytic activities of Fe3(btc)2 and
      Cu3(btc)2. The activation energy of the rate-determining step is almost 2 times
      lower for Fe3(btc)2 than that for Cu3(btc)2, due to a larger charge transfer from
      the catalytic site to the O2 molecule in the case of Fe3(btc)2.

PMID- 29457811
TI  - Liquid crystalline behaviour of self-assembled LAPONITE(r)/PLL-PEG
      nanocomposites.
AB  - Synthetic LAPONITE(r)-clay particles with platelet-like shape display strong
      aging when dispersed in aqueous solutions, preventing the latter from reaching
      their natural liquid-crystalline equilibrium state. Here we introduce a facile
      method that successfully prevents this aging behaviour and enables accessing the
      systems' liquid-crystal and crystalline phases. We graft the comb-like polymer
      PLL-PEG (poly(l-lysine)-g-poly(ethylene glycol)) onto the clay surfaces from
      solution, thereby screening the negative surface charges and thus ensuring steric
      stabilisation. We show zeta-sizer and rheology measurements, respectively,
      confirming complete steric coating and that aging of dilute samples is completely
      suppressed even after a year. Using evaporation as a means to concentrate the
      particles, we observe various liquid crystalline textures under a polarized
      optical microscope (POM). Upon sequential spreading and drying, we are also able
      to obtain transparent films with hierarchical architecture.

PMID- 29457812
TI  - Diffusive interaction of multiple surface nanobubbles: shrinkage, growth, and
      coarsening.
AB  - Surface nanobubbles are nanoscopic spherical-cap shaped gaseous domains on
      immersed substrates which are stable, even for days. After the stability of a
      single surface nanobubble has been theoretically explained, i.e. contact line
      pinning and gas oversaturation are required to stabilize it against diffusive
      dissolution [Lohse and Zhang, Phys. Rev. E, 2015, 91, 031003(R)], here we focus
      on the collective diffusive interaction of multiple nanobubbles. For that purpose
      we develop a finite difference scheme for the diffusion equation with the
      appropriate boundary conditions and with the immersed boundary method used to
      represent the growing or shrinking bubbles. After validation of the scheme
      against the exact results of Epstein and Plesset for a bulk bubble [J. Chem.
      Phys., 1950, 18, 1505] and of Lohse and Zhang for a surface bubble, the framework
      of these simulations is used to describe the coarsening process of competitively
      growing nanobubbles. The coarsening process for such diffusively interacting
      nanobubbles slows down with advancing time and increasing bubble distance. The
      present results for surface nanobubbles are also applicable for immersed surface
      nanodroplets, for which better controlled experimental results of the coarsening
      process exist.

PMID- 29457813
TI  - Copper-catalyzed synthesis of alpha-amino nitriles through methyl transfer from
      DMF to aromatic amines.
AB  - A copper-catalyzed activation of C(sp3)-H bonds of DMF at room temperature was
      developed, which results in methyl transfer to aromatic amines for efficient
      synthesis of exceedingly valuable alpha-amino nitriles. This process features
      excellent functional group tolerance, a broad substrate scope, and high activity
      under ambient conditions.

PMID- 29457814
TI  - An electrophilic reagent for the synthesis of OCHFMe-containing molecules.
AB  - Herein the synthesis of a novel and bench stable electrophilic reagent to
      construct the OCFHMe motif from O-nucleophiles has been described. This sulfonium
      salt, readily obtained in 5 steps, reacted with various phenols and alcohols. The
      resulting products, including complex molecules, were obtained in good yields.
      This reagent was also used for the functionalization of thiol derivatives.

PMID- 29457815
TI  - Hydrogen bonding effect between active site and protein environment on catalysis
      performance in H2-producing [NiFe] hydrogenases.
AB  - The interaction between the active site and the surrounding protein environment
      plays a fundamental role in the hydrogen evolution reaction (HER) in [NiFe]
      hydrogenases. Our density functional theory (DFT) findings demonstrate that the
      reaction Gibbs free energy required for the rate determining step decreases by
      7.1 kcal mol-1 when the surrounding protein environment is taken into account,
      which is chiefly due to free energy decreases for the two H+/e- addition steps
      (the so-called Ni-SIa to I1, and Ni-C to Ni-R), being the largest thermodynamic
      impediments of the whole reaction. The variety of hydrogen bonds (H-bonds)
      between the amino acids and the active site is hypothesised to be the main reason
      for such stability: H-bonds not only work as electrostatic attractive forces that
      influence the charge redistribution, but more importantly, they act as an
      electron 'pull' taking electrons from the active site towards the amino acids.
      Moreover, the electron 'pull' effect through H-bonds via the S- in cysteine
      residues shows a larger influence on the energy profile than that via the CN-
      ligands on Fe.

PMID- 29457816
TI  - Iodine promoted dual oxidative C(sp3)-H amination of 2-methyl-3-arylquinazolin
      4(3H)-ones: a facile route to 1,4-diarylimidazo[1,5-a]quinazolin-5(4H)-ones.
AB  - An iodine promoted tandem oxidative condensation of benzylamines and 2
      methylquinazolin-4-(3H)-ones was developed to yield imidazo[1,5-a]quinazolin
      5(4H)-ones via dual C(sp3)-H amination under metal free conditions in a greener
      way using molecular oxygen as a terminal oxidant. This tandem transformation
      provides an efficient approach to construct various functionalized imidazo[1,5
      a]quinazolin-5(4H)-ones in a straightforward manner via a sequential amination
      oxidation-annulation-aromatisation.

PMID- 29457817
TI  - Electron transfer rate analysis of a site-specifically wired copper oxidase.
AB  - Electron transfer kinetic parameters of site-specifically wired copper oxidase
      were investigated. The enzyme's orientation towards the electrode was controlled
      by incorporation of propargyl-l-lysine as a site-specific anchoring point.
      Herein, we demonstrate the importance of immobilization orientation and how it
      affects electron transfer efficiency and kinetics to each of the enzyme's two
      active sites.

PMID- 29457818
TI  - Light-enhanced acid catalysis over a metal-organic framework.
AB  - A Bronsted acid-functionalized metal-organic framework (MOF), MIL-101-SO3H, was
      prepared for acid-engaged esterification reactions. Strikingly, for the first
      time, the MOF exhibits significantly light-enhanced activity and possesses
      excellent activity and recyclability, with even higher activity than H2SO4 under
      light irradiation.

PMID- 29457819
TI  - Expedient cobalt(ii)-catalyzed site-selective C7-arylation of indolines with
      arylboronic acids.
AB  - Cobalt(ii)-catalyzed pyrimidyl directing group-assisted C7 arylation of indolines
      with arylboronic acids has been developed using Mn(OAc)2.4H2O as an oxidant. The
      use of cobalt(ii)-PCy3 as a catalyst and broad substrate scope are the important
      practical features.

PMID- 29457822
TI  - A nitrogen-rich ligand as a scaffold for slow magnetic relaxation in dysprosium
      based 0D and 1D architectures.
AB  - A recently designed nitrogen-rich ligand is successfully applied as a scaffold
      for lanthanide ions to show that the intricate chemistry of energetic materials
      can be combined with other fields of research, including that of molecular
      magnetism. Herein, we report the synthesis of two different types of molecular
      architectures using a single ligand template, in which the discrete monomer
      exhibits single-molecule magnet-like behaviour along with two well-isolated modes
      of magnetic relaxation.

PMID- 29457824
TI  - Understanding the conformational analysis of gababutin based hybrid peptides.
AB  - Constrained gamma-amino acid gababutin (Gbn) based peptides that form different
      conformations have been synthesized. Striving to rationalize the impact of side
      chain orientations framing tetrapeptide-based supramolecular organic frameworks
      and morphological entities, Gbn incorporated hybrid peptides Boc-Gbn-Aib-Aaa-Aib
      OMe (where Aaa = Phe(F) for peptide 1, Leu(L) for peptide 2 and Tyr(Y) for
      peptide 3) were synthesized by changing the amino acid at the third position. The
      solution state dual folded conformation (C12/C10 H-bonded) is probed by 2D NMR
      spectroscopy in support of a DMSO-d6 titration and VT NMR experiments. Peptides 1
      3 adopt a C12/C10 type H-bonded dual folded conformation in the crystal state. In
      addition, distinct supramolecular frameworks result from the modification and
      orientation of the third residue side chain of peptides 1-3. A solvent induced
      morphological diversity of peptides 1-3 is attained by modifying the side chain
      backbone of the tetrapeptides, which are investigated by various microscopic (SEM
      and AFM) studies. Gbn-based peptides 1-3 show significant morphological and
      supramolecular packing properties, which are fairly different from those of their
      gabapentin (Gpn) based analogue peptides.

PMID- 29457826
TI  - Prevalence of cardiometabolic risk factors among professional male long-distance
      bus drivers in Lagos, south-west Nigeria: a cross-sectional study.
AB  - BACKGROUND: Professional drivers are known to be at high risk of cardiovascular
      disease (CVD). This study was carried out to highlight these risk factors and
      their predictors among male long-distance professional bus drivers in Lagos,
      south-west Nigeria, with a view to improving health awareness in this group.
      METHOD: Socio-demographic data, anthropometric indices, blood pressure, fasting
      plasma blood glucose levels and lipid and physical activity profiles of 293
      drivers were measured. RESULTS: Mean age of the study population was 48 +/- 9.7
      years; 71.0 and 19.5% of the drivers used alcohol and were smokers, respectively;
      and 50.9% were physically inactive. The prevalence of overweight and obesity was
      41.7 and 21.1%, respectively, while 39.7 and 13.9% were hypertensive and
      diabetic, respectively. Ninety (31.3%) subjects had impaired fasting glucose
      levels while 56.3% had dyslipidaemia. Predictors of hypertension were age and
      body mass index (BMI). BMI only was a predictor of abnormal glucose profile.
      CONCLUSION: Professional male long-distance bus drivers in this study showed a
      high prevalence of a cluster of risk factors for CVD.

PMID- 29457827
TI  - Percutaneous transmitral balloon commissurotomy using a single balloon with
      arteriovenous loop stabilisation: an alternative when there is no Inoue balloon.
AB  - BACKGROUND: The Inoue balloon technique is the standard technique for mitral
      valve balloon commissurotomy at this stage. However, the hardware for this
      technique is expensive and may not always be available in resource-limited
      settings. OBJECTIVE: This article reports our experience with percutaneous
      transmitral balloon commissurotomy using a single balloon (Nucleus) with
      arteriovenous loop stabilisation. METHOD: Eleven young patients, aged 12-26 years
      and weighing 23-48 kg, underwent transmitral balloon commissurotomy using the
      described technique at our centre from April to May 2014. RESULTS: Mean
      fluoroscopy time was 22.6 +/- 6.4 min (18.5- 30.0). Mean transmitral gradient
      decreased from 24.1 +/- 5.9 (16-35) to 6.6 +/- 3.8 (3-14) mmHg, as measured on
      transoesophageal echocardiography. Mean mitral valve area increased from 0.69 +/-
      0.13 cm2 (range 0.5-0.9) before dilation to 1.44 +/- 0.25 cm2 (1.1-1.9) after
      dilation (p < 0.001). Mean estimated pulmonary artery systolic pressure decreased
      from 110.0 +/- 35 mmHg (75-170) before dilation to 28.0 +/- 14.4 mmHg (range 10
      60) after dilation. CONCLUSION: Our modified Nucleus balloon technique for mitral
      valve dilation in young patients with mitral stenosis is effective and safe. The
      technique differs from other over-the-wire techniques in that it avoids placing
      stiff wire in the left ventricle. It also offers better balloon stability and
      control owing to the arteriovenous loop. This technique may be easier for use by
      paediatric interventionists who might not be familiar with the Inoue balloon
      technique.

PMID- 29457829
TI  - Species-specific susceptibility to cannabis-induced convulsions.
AB  - BACKGROUND AND PURPOSE: Numerous claims are made for cannabis' therapeutic
      utility upon human seizures, but concerns persist about risks. A potential
      confounder is the presence of both Delta9 -tetrahydrocannabinol (THC), variously
      reported to be pro- and anticonvulsant, and cannabidiol (CBD), widely confirmed
      as anticonvulsant. Therefore, we investigated effects of prolonged exposure to
      different THC/CBD cannabis extracts on seizure activity and associated measures
      of endocannabinoid (eCB) system signalling. EXPERIMENTAL APPROACH: Cannabis
      extract effects on in vivo neurological and behavioural responses, and on
      bioanalyte levels, were measured in rats and dogs. Extract effects on seizure
      activity were measured using electroencephalography telemetry in rats. eCB
      signalling was also investigated using radioligand binding in cannabis extract
      treated rats and treatment-naive rat, mouse, chicken, dog and human tissue. KEY
      RESULTS: Prolonged exposure to cannabis extracts caused spontaneous, generalized
      seizures, subserved by epileptiform discharges in rats, but not dogs, and
      produced higher THC, but lower 11-hydroxy-THC (11-OH-THC) and CBD, plasma
      concentrations in rats versus dogs. In the same rats, prolonged exposure to
      cannabis also impaired cannabinoid type 1 receptor (CB1 receptor)-mediated
      signalling. Profiling CB1 receptor expression, basal activity, extent of
      activation and sensitivity to THC suggested interspecies differences in eCB
      signalling, being more pronounced in a species that exhibited cannabis extract
      induced seizures (rat) than one that did not (dog). CONCLUSIONS AND IMPLICATIONS:
      Sustained cannabis extract treatment caused differential seizure, behavioural and
      bioanalyte levels between rats and dogs. Supporting radioligand binding data
      suggest species differences in eCB signalling. Interspecies variations may have
      important implications for predicting cannabis-induced convulsions from animal
      models.

PMID- 29457828
TI  - Dihydrodiosgenin protects against experimental acute pancreatitis and associated
      lung injury through mitochondrial protection and PI3Kgamma/Akt inhibition.
AB  - BACKGROUND AND PURPOSE: Acute pancreatitis (AP) is a painful and distressing
      disorder of the exocrine pancreas with no specific treatment. Diosgenyl saponins
      extracted from from Dioscorea zingiberensis C. H. Wright have been reported to
      protect against experimental models of AP. Diosgenin, or its derivatives are anti
      inflammatory in various conditions. However, the effects of diosgenin and its
      spiroacetal ring opened analogue, dihydrodiosgenin (Dydio), on AP have not been
      determined. EXPERIMENTAL APPROACH: Effects of diosgenin and Dydio on sodium
      taurocholate hydrate (Tauro)-induced necrosis were tested, using freshly isolated
      murine pancreatic acinar cells. Effects of Dydio on mitochondrial dysfunction in
      response to Tauro, cholecystokinin-8 and palmitoleic acid ethyl ester were also
      assessed. Dydio (5 or 10 mg.kg-1 ) was administered after the induction in vivo
      of Tauro-induced AP (Wistar rats), caerulein-induced AP and palmitoleic acid plus
      ethanol-induced AP (Balb/c mice). Pancreatitis was assessed biochemically and
      histologically. Activation of pancreatic PI3Kgamma/Akt was measured by
      immunoblotting. KEY RESULTS: Dydio inhibited Tauro-induced activation of the
      necrotic cell death pathway and prevented pancreatitis stimuli-induced
      mitochondrial dysfunction. Therapeutic administration of Dydio ameliorated
      biochemical and histopathological responses in all three models of AP through
      pancreatic mitochondrial protection and PI3Kgamma/Akt inactivation. Moreover,
      Dydio improved pancreatitis-associated acute lung injury through preventing
      excessive inflammatory responses. CONCLUSION AND IMPLICATIONS: These data provide
      in vitro and in vivo mechanistic evidence that the diosgenin analogue, Dydio
      could be potential treatment for AP. Further medicinal optimization of diosgenin
      and its analogue might be a useful strategy for identifying lead candidates for
      inflammatory diseases.

PMID- 29457830
TI  - miRNA-124-3p/neuropilin-1(NRP-1) axis plays an important role in mediating
      glioblastoma growth and angiogenesis.
AB  - Glioblastoma multiforme (GBM) is the most lethal brain malignancy which involves
      multi-gene abnormality. Unfortunately, effective therapy against GBM remains
      lacking. Previously, we found that NRP-1 and its downstream NRP-1/GIPC1 pathway
      played an important role in GBM. In our study, we further investigated the
      upstream signaling of NRP-1 to understand how it is regulated. First, we
      identified that hsa-miR-124-3p was miRNA differentially expressed in GBM and in
      normal brain tissues by high-throughput sequencing. Then, by dual luciferase
      reporter gene, we found miR-124-3p can specially bind to the 3'UTR region of the
      NRP-1 thus suppresses its expression. Moreover, miR-124-3p overexpression
      significantly inhibited GBM cell proliferation, migration and tumor angiogenesis
      which resulted in GBM apoptosis and cell cycle arrest, putatively via NRP-1
      mediated PI3K/Akt/NFkappaB pathways activation in GBM cells. Meanwhile, miR-124
      3p overexpression also suppressed tumor growth and reduced tumor angiogenesis
      when targeted by NRP-1 in a PDX model. Furthermore, NRP-1 mAb exerted synergistic
      inhibitory effects with miR-124-3p overexpression in GBM. Thus, we discovered
      that miR-124-3p acts as the upstream suppressor of NRP-1 which promotes GBM cell
      development and growth by PI3K/Akt/NFkappaB pathway. The miR-124-3p/NRP-1/GIPC1
      pathway as a new pathway has a vital role in GBM, and it could be considered as
      the potential target for malignant gliomas in future.

PMID- 29457831
TI  - Low T3 syndrome as a predictor of poor prognosis in chronic lymphocytic leukemia.
AB  - Low triiodothyronine (T3) state is associated with poor prognosis in critical
      acute and prolonged illness. However, the information on thyroid dysfunction and
      cancer is limited. The aim of our study was to evaluate the prognostic value of
      low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty
      eight patients with detailed thyroid hormone profile at CLL diagnosis were
      enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by
      normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH)
      levels. A propensity score-matched method was performed to balance the baseline
      characteristics. Multivariate Cox regression analyses screened the independent
      prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific
      survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of
      CLL-International Prognostic Index (IPI) together with low T3 syndrome. The
      results showed that 37 (14.34%) patients had low T3 syndrome, which was
      significantly associated with unfavorable TTFT and CSS in the propensity-matched
      cohort, and it was an independent prognostic indicator for both TTFT and CSS.
      Serum FT3 level was positively related to protein metabolism and anemia, and
      inversely related to inflammatory state. Patients with only low FT3 demonstrated
      better survival than those with synchronously low FT3 and FT4, while those with
      synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3
      syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in
      TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate
      for predicting prognosis in future clinical practice of CLL.

PMID- 29457832
TI  - Preferential conduction in arrhythmia ablation.

PMID- 29457833
TI  - A Green Method to Determine VUV (185 nm) Fluence Rate Based on Hydrogen Peroxide
      Production in Aqueous Solution.
AB  - A mini-fluidic vacuum ultraviolet/ultraviolet (VUV/UV) photoreaction system
      (MVPS) was developed in our previous study. Based on the MVPS, a green method to
      determine VUV fluence rate has been developed using the production rate of H2 O2
      when water is exposed to 185 nm VUV. The H2 O2 production followed pseudo-zero
      order reaction kinetics well over the first 10 min of VUV/UV exposure. This new
      method was well calibrated with a standard cis-cyclooctene cis-trans
      photoisomerization actinometer as recommended by the International Union of Pure
      and Applied Chemistry. The apparent quantum yield for H2 O2 production by 185 nm
      VUV irradiation of water was determined to be 0.024 +/- 0.002. As the solution pH
      increased from 5.0 to 8.0, the H2 O2 production rate decreased from 0.83 to 0.40
      MUm min-1 . Dissolved oxygen had a negligible influence on the H2 O2 production.
      This study proposes a novel VUV fluence rate determination method with advantages
      of nontoxicity, low detection limits, low costs and convenience, and it can be
      used as a good alternative to traditional actinometers.

PMID- 29457834
TI  - Limitations to ablation of the vanishing PVC using pace-mapping response to
      comment about preferential conduction in arrhythmia ablation.

PMID- 29457835
TI  - Tumoroid a la carte: Path for personalization.

PMID- 29457837
TI  - Improved Wound Remodeling Correlates with Modulated TGF-beta Expression in Skin
      Diabetic Wounds Following Combined Red and Infrared Photobiomodulation
      Treatments.
AB  - Diabetic wounds are a major cause of morbidity among patients with poorly
      controlled blood glucose levels. Conventional empirical wound care strategies
      have shown limited efficacy, and there is an urgent need to develop novel
      therapeutic strategies. Photobiomodulation treatments have shown positive
      therapeutic effects in several cell culture and animal models. In this study, we
      examined wound healing in diabetic rats following treatments with two laser
      wavelengths, namely red (660 nm) and infrared (808 nm) individually and in
      combination as compared to routine wound dressings. Immunostaining for TGF-beta
      expression was performed at various times postwounding. We noted that the
      combination of red and infrared laser treatments correlated with decreased TGF
      beta1 levels at late stages in healing. There was no statistical significance
      with any treatments at an earlier time point. This study emphasizes the role of
      appropriate laser treatment protocols in modulating wound healing and remodeling
      responses.

PMID- 29457836
TI  - DEP domain-containing mTOR-interacting protein suppresses lipogenesis and
      ameliorates hepatic steatosis and acute-on-chronic liver injury in alcoholic
      liver disease.
AB  - : Alcoholic liver disease (ALD) is characterized by lipid accumulation and liver
      injury. However, how chronic alcohol consumption causes hepatic lipid
      accumulation remains elusive. The present study demonstrates that activation of
      the mechanistic target of rapamycin complex 1 (mTORC1) plays a causal role in
      alcoholic steatosis, inflammation, and liver injury. Chronic-plus-binge ethanol
      feeding led to hyperactivation of mTORC1, as evidenced by increased
      phosphorylation of mTOR and its downstream kinase S6 kinase 1 (S6K1) in
      hepatocytes. Aberrant activation of mTORC1 was likely attributed to the defects
      of the DEP domain-containing mTOR-interacting protein (DEPTOR) and the
      nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 (SIRT1) in the
      liver of chronic-plus-binge ethanol-fed mice and in the liver of patients with
      ALD. Conversely, adenoviral overexpression of hepatic DEPTOR suppressed mTORC1
      signaling and ameliorated alcoholic hepatosteatosis, inflammation, and acute-on
      chronic liver injury. Mechanistically, the lipid-lowering effect of hepatic
      DEPTOR was attributable to decreased proteolytic processing, nuclear
      translocation, and transcriptional activity of the lipogenic transcription factor
      sterol regulatory element-binding protein-1 (SREBP-1). DEPTOR-dependent
      inhibition of mTORC1 also attenuated alcohol-induced cytoplasmic accumulation of
      the lipogenic regulator lipin 1 and prevented alcohol-mediated inhibition of
      fatty acid oxidation. Pharmacological intervention with rapamycin alleviated the
      ability of alcohol to up-regulate lipogenesis, to down-regulate fatty acid
      oxidation, and to induce steatogenic phenotypes. Chronic-plus-binge ethanol
      feeding led to activation of SREBP-1 and lipin 1 through S6K1-dependent and
      independent mechanisms. Furthermore, hepatocyte-specific deletion of SIRT1
      disrupted DEPTOR function, enhanced mTORC1 activity, and exacerbated alcoholic
      fatty liver, inflammation, and liver injury in mice. CONCLUSION: The
      dysregulation of SIRT1-DEPTOR-mTORC1 signaling is a critical determinant of ALD
      pathology; targeting SIRT1 and DEPTOR and selectively inhibiting mTORC1-S6K1
      signaling may have therapeutic potential for treating ALD in humans. (Hepatology
      2018).

PMID- 29457838
TI  - Bax inhibitor-1 protects from nonalcoholic steatohepatitis by limiting inositol
      requiring enzyme 1 alpha signaling in mice.
AB  - : Endoplasmic reticulum (ER) stress is activated in nonalcoholic fatty liver
      disease (NAFLD), raising the possibility that ER stress-dependent metabolic
      dysfunction, inflammation, and cell death underlie the transition from steatosis
      to steatohepatitis (nonalcoholic steatohepatitis; NASH). B-cell lymphoma 2 (BCL2)
      associated X protein (Bax) inhibitor-1 (BI-1), a negative regulator of the ER
      stress sensor, inositol-requiring enzyme 1 alpha (IRE1alpha), has yet to be
      explored in NAFLD as a hepatoprotective agent. We hypothesized that the genetic
      ablation of BI-1 would render the liver vulnerable to NASH because of
      unrestrained IRE1alpha signaling. ER stress was induced in wild-type and BI-1-/-
      mice acutely by tunicamycin (TM) injection (1 mg/kg) or chronically by high-fat
      diet (HFD) feeding to determine NAFLD phenotype. Livers of TM-treated BI-1-/-
      mice showed IRE1alpha-dependent NOD-like receptor family, pyrin domain containing
      3 (NLRP3) inflammasome activation, hepatocyte death, fibrosis, and dysregulated
      lipid homeostasis that led to liver failure within a week. The analysis of human
      NAFLD liver biopsies revealed BI-1 down-regulation parallel to the up-regulation
      of IRE1alpha endoribonuclease (RNase) signaling. In HFD-fed BI-1-/- mice that
      presented NASH and type 2 diabetes, exaggerated hepatic IRE1alpha, X-box binding
      protein 1 (XBP1), and C/EBP homologous protein (CHOP) expression was linked to
      activated NLRP3 inflammasome and caspase-1/-11. Rises in interleukin (IL)-1beta,
      IL-6, monocyte chemoattractant protein 1 (MCP1), chemokine (C-X-C motif) ligand 1
      (CXCL1), and alanine transaminase (ALT)/aspartate transaminase (AST) levels
      revealed significant inflammation and injury, respectively. Pharmacological
      inhibition of IRE1alpha RNase activity with the small molecules, STF-083010 or
      4MU8c, was evaluated in HFD-induced NAFLD. In BI-1-/- mice, either treatment
      effectively counteracted IRE1alpha RNase activity, improving glucose tolerance
      and rescuing from NASH. The hepatocyte-specific role of IRE1alpha RNase activity
      in mediating NLRP3 inflammasome activation and cell death was confirmed in
      primary mouse hepatocytes by IRE1alpha axis knockdown or its inhibition with STF
      083010 or 4MU8c. CONCLUSION: Targeting IRE1alpha-dependent NLRP3 inflammasome
      signaling with pharmacological agents or by BI-1 may represent a tangible
      therapeutic strategy for NASH. (Hepatology 2018).

PMID- 29457839
TI  - Brincidofovir as Salvage Therapy for Adenovirus Disease in Intestinal Transplant
      Recipients.
AB  - BACKGROUND: Adenoviruses are double-stranded DNA viruses that typically cause
      mild self-limiting respiratory, ocular, and gastrointestinal infections. In
      immunocompromised patients, especially transplant recipients, the infection can
      be severe, with dissemination and multiorgan failure. In intestinal transplant
      recipients, the incidence is as high as 57%. To our knowledge, no standardized
      guidelines or U.S. Food and Drug Administration-approved medications exist for
      the treatment of adenovirus disease. AIMS: We describe two isolated intestinal
      transplant recipients who developed adenovirus disease (viremia with viral
      enteritis) that was managed with a new experimental drug, brincidofovir (an oral
      lipid conjugate prodrug of cidofovir), as salvage therapy. RESULTS: The first
      patient was a 44-year-old woman who developed adenoviral enteritis 1 month after
      transplantation, which resolved with ribavirin therapy. Two weeks later, the
      infection recurred, and brincidofovir was initiated. While receiving this therapy
      for 3 months, she developed severe acute rejection, which was managed with rabbit
      antithymocyte globulin followed by infliximab. Eventually, complete resolution of
      the rejection and adenoviral enteritis was achieved. At 12 months
      posttransplantation, the patient was healthy and tolerating enteral feeding. The
      second patient was a 28-year-old man who had undergone isolated intestinal
      transplantation 6 years before he presented with generalized weakness and an
      increased ostomy output; he was diagnosed with adenoviral enteritis. Maintenance
      immunosuppression was reduced, and brincidofovir was started. The infection
      resolved with a month of therapy. Six months after the infection, he was healthy
      and tolerating enteral feeding. CONCLUSION: This is the first publication, to our
      knowledge, to describe two cases in which brincidofovir was used to successfully
      treat adenovirus infection in intestinal transplant recipients. Thus, these cases
      demonstrate that brincidofovir appears to be a safe and effective option in the
      management of adenoviral enteritis in these patients.

PMID- 29457841
TI  - Erectile dysfunction: they don't talk, we don't ask.

PMID- 29457840
TI  - Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult
      patients with atrial fibrillation.
AB  - AIMS: This study aimed to analyse the effects of genetic polymorphisms in drug
      transporters and metabolizing enzymes, and clinical laboratory data on the
      pharmacokinetic parameters of apixaban. METHODS: Data were collected from 81
      Japanese patients with atrial fibrillation. Pharmacogenomic data were stratified
      by ABCB1, ABCG2 and CYP3A5 polymorphisms. The pharmacokinetic profile of apixaban
      was described by a one-compartment model with first-order absorption. Population
      pharmacokinetic analysis was conducted using a nonlinear mixed effect modelling
      (NONMEMTM) program. RESULTS: The nonlinear relationship between oral clearance
      (CL/F) of apixaban and creatinine clearance (Ccr) was observed. The population
      mean of CL/F for a typical patient (Ccr value of 70 ml min-1 ) with the
      CYP3A5*1/*1 and ABCG2 421C/C or C/A genotypes was estimated to be 3.06 l h-1 .
      When Ccr values were set to the typical value, the population mean of CL/F was
      1.52 times higher in patients with the CYP3A5*1/*1 genotype compared with
      patients with the CYP3A5*1/*3 or *3/*3 genotype, while the population mean of
      CL/F was 1.49 times higher in patients with the ABCG2 421C/C or C/A genotype
      compared with patients with the ABCG2 421A/A genotype. However, no covariates
      affected the population mean of the apparent volume of distribution (Vd/F) of
      apixaban. The population mean of Vd/F was estimated to be 24.7 l. CONCLUSION: The
      present study suggests that the ABCG2 421A/A and CYP3A5*3 genotypes and renal
      function are intrinsic factors affecting apixaban pharmacokinetics. These
      findings may provide useful information for precision medicine using apixaban, to
      avoid the risk of adverse reactions.

PMID- 29457842
TI  - Long-term outcomes of patients undergoing simultaneous liver transplantation and
      sleeve gastrectomy.
AB  - : Obesity is increasingly common before and after liver transplantation (LT), yet
      optimal management remains unclear. The aim of this study was to analyze the long
      term outcomes for obese patients undergoing LT, including a noninvasive weight
      loss program and combined LT and sleeve gastrectomy (SG). Since 2006, all
      patients referred for LT with a body mass index (BMI) >=35 kg/m2 were enrolled.
      Patients who achieved weight loss (BMI <35) underwent LT alone, and those who did
      not underwent simultaneous LT + SG. Analysis of long-term outcomes for patients
      >=3 years posttransplant was performed. Since 2006, there were 36 in the weight
      loss intervention (LT cohort) and 13 in the LT + SG cohort with >3 years of
      follow-up, whereas overall, a total of 29 patients underwent LT + SG. Patients in
      the LT cohort had less severe obesity at enrollment (40.0 +/- 2.7 vs. LT + SG
      cohort 46.0 +/- 4.5; P < 0.001). In the LT cohort, 83.3% (30 of 36) achieved >10%
      loss in total body weight (TBW) pre-LT. Three years posttransplant, 29.4% of
      patients in the LT cohort maintained >10% loss in TBW, whereas 100% of the LT +
      SG patients did (P < 0.001). Patients who underwent LT + SG maintained a
      significantly higher percentage of total body weight loss after 3 years of follow
      up (LT cohort 3.9 +/- 13.3% vs. LT + S G cohort 34.8 +/- 17.3%; P < 0.001).
      Patients in the LT + SG also had a lower prevalence of hypertension, insulin
      resistance, and hepatic steatosis and required fewer antihypertensive medications
      and lipid agents at last follow-up. CONCLUSION: Whereas weight loss before
      transplantation was achieved by obese patients, weight regain was common in the
      LT cohort. Combined LT + SG resulted in more effective and more durable weight
      loss, as well as fewer metabolic complications at last follow-up. (Hepatology
      2018).

PMID- 29457843
TI  - The tumour-stroma ratio in colon cancer: the biological role and its prognostic
      impact.
AB  - The tumour microenvironment consists of a complex mixture of non-neoplastic
      cells, including fibroblasts, immune cells and endothelial cells embedded in the
      proteins of the extracellular matrix. The tumour microenvironment plays an active
      role in tumour behaviour. By interacting with cancer cells, it influences disease
      progression and the metastatic capacity of the tumour. Tumours with a high amount
      of stroma correspond to poor patient prognosis. The tumour-stroma ratio (TSR) is
      a strong independent prognostic tool in colon cancer and provides additional
      value to the current clinically used tumour-node-metastasis classification. The
      TSR is assessed on conventional haematoxylin and eosin-stained paraffin sections
      at the invasive front of the tumour. Here we review studies demonstrating the
      prognostic significance of the TSR in solid epithelial tumours with a focus on
      colon cancer. Moreover, the biological role of the tumour microenvironment during
      tumour progression and invasion will be discussed, as well as the attempts to
      target the tumour stroma for therapeutic purposes. We suggest that the TSR can be
      implemented with little effort and without additional costs in current routine
      pathology diagnostics owing to its simplicity and reliability.

PMID- 29457844
TI  - Effect of type D personality on smoking status and their combined impact on
      outcome after acute myocardial infarction.
AB  - BACKGROUND: Smoking cessation is correlated with several psychological, social,
      biological, and pharmacological aspects. The combined tendency to experience
      negative emotions and to inhibit the expression of these emotions is indicated as
      "type D personality," an independent risk marker for clinical outcome in cardiac
      disease. Despite this effect of type D personality on cardiovascular disease, it
      is still unclear whether this personality trait may influence smoking cessation
      after a myocardial infarction. HYPOTHESIS: we hypothesized that there is a
      relationship between type D personality and smoking persistence in acute coronary
      syndrome patients, and this association may predict a worse long-term prognosis.
      METHODS: The study enrolled 231 patients with ST-segment elevation myocardial
      infarction, treated with primary percutaneous coronary intervention. Type D scale
      14 (ds 14) was administered upon admission to the hospital. RESULTS: After
      controlling for demographic and clinical confounders, non-type D patients
      reported statistically significant higher frequencies of smoking cessation when
      compared with the type D group. In addition, the presence of this psychological
      factor anticipates significantly the onset of smoking during adolescence.
      Furthermore, current type D smokers had a higher incidence of cardiovascular
      events during long-term follow-up. CONCLUSIONS: Type D personality and smoking
      status increase the risk of cardiac events. An emotionally stressed personality
      and persistence of smoking after the first cardiac event, and mostly their mutual
      influence, indicate a population at high cardiovascular risk.

PMID- 29457845
TI  - Reply to "Excess amyloid beta can be degraded in healthy humans".

PMID- 29457846
TI  - Dispositional malevolence and impression formation: Dark Tetrad associations with
      accuracy and positivity in first impressions.
AB  - OBJECTIVE: The Dark Tetrad traits (subclinical psychopathy, narcissism,
      Machiavellianism, and everyday sadism) have interpersonal consequences. At
      present, however, how these traits are associated with the accuracy and
      positivity of first impressions is not well understood. The present article
      addresses three primary questions. First, to what extent are perceiver levels of
      Dark Tetrad traits associated with differing levels of perceptive accuracy?
      Second, to what extent are target levels of Dark Tetrad traits associated with
      differing levels of expressive accuracy? Finally, to what extent can Dark Tetrad
      traits be differentiated when examining perceptions of and by others? METHOD: In
      a round-robin design, undergraduate participants (N = 412) in small groups
      engaged in brief, naturalistic, unstructured dyadic interactions before providing
      impressions of their partner. RESULTS: Dark Tetrad traits were associated with
      being viewed and viewing others less distinctively accurately and more
      negatively. CONCLUSIONS: Interpersonal perceptions that included an individual
      scoring highly on one of the Dark Tetrad traits differed in important ways from
      interactions among individuals with more benevolent personalities. Notably,
      despite the similarities between the Dark Tetrad, traits had unique associations
      with interpersonal perceptions.

PMID- 29457847
TI  - Preconditioning With Low-Level Laser Irradiation Enhances the Therapeutic
      Potential of Human Adipose-derived Stem Cells in a Mouse Model of Photoaged Skin.
AB  - This study was conducted to explore the therapeutic potential of human adipose
      derived stem cells (ADSCs) irradiated with a low-level laser (LLL). Cultured
      ADSCs were treated with 650-nm GaAlAs laser irradiation at 2, 4 and 8 J cm-2 .
      Cell proliferation was quantified by MTT assays, cytokine secretion was
      determined by enzyme-linked immunosorbent assays, and adipogenic differentiation
      was examined by oil red O staining. Additionally, the expression profiles of
      putative ADSC surface markers were analyzed by quantitative real-time PCR. In
      addition, a mouse photoaged skin model was established by UVB irradiation.
      Effects of GaAlAs laser-treated ADSCs on the thicknesses of the epidermis and
      dermis were analyzed by hematoxylin and eosin staining. The results showed that
      GaAlAs laser treatment of cells at a radiant exposure of 4 J cm-2 enhanced ADSC
      proliferation and adipogenic differentiation and increased secretion of growth
      factors. Furthermore, GaAlAs laser irradiation upregulated the expression of
      putative ADSC surface markers. In the mouse model of photoaged skin, ADSCs
      treated with GaAlAs laser irradiation had markedly decreased the epidermal
      thickness and increased the dermal thickness of photoaged mouse skin. Our data
      indicate that LLL irradiation is an effective biostimulator of ADSCs and might
      enhance the therapeutic potential of ADSCs for clinical use.

PMID- 29457848
TI  - Effects of chronic heat exposure on growth performance, intestinal epithelial
      histology, appetite-related hormones and genes expression in broilers.
AB  - BACKGROUND: Heat stress often occurs in the modern poultry industry, which
      impairs growth performance, particularly via reducing appetite. This study was
      aimed to investigate the mechanism of attenuating appetite by chronic heat
      exposure in broilers. A total of 144 broilers (28 days old) were allocated to
      normal control (NC, 22  degrees C), heat stress (32  degrees C), and pair-fed (22
      degrees C) groups. RESULTS: Chronic heat exposure significantly increased
      cloacal temperatures and respiration rates, decreased the average daily feed
      intake and average daily gain, increased feed-to-gain ratio compared with the NC
      group, and elevated the concentrations of ghrelin and cholecystokinin (CCK) both
      in serum and intestine, as well as peptide YY and somatostatin in intestine on 35
      or 42-day-old broilers. Moreover, heat exposure decreased villi height (VH) and
      the ratio of VH to crypt depth (CD), while it increased CD in the jejunum on 35-
      and 42 day-olds, increased (P < 0.05) the concentrations of valine and isoleucine
      in plasma on 42 days, and upregulated (P < 0.05) the expression of taste receptor
      type 1 members 1 and 3 (T1R1 and T1R3), CCK, and ghrelin in the intestine on 35-
      or 42-day-old broilers. CONCLUSION: Chronic heat exposure impairs the
      performance, intestinal morphology and appetite, which may be correlated with the
      increased secretion or gene expression of appetite-related hormones and genes,
      and the higher expression of nutrient-sensing receptors (T1R1 and T1R3) in
      broilers. (c) 2018 Society of Chemical Industry.

PMID- 29457849
TI  - Tobacco-attributable burden of cancer according to socioeconomic position in
      France.
AB  - Smoking is a major preventable cause of cancers and is increasingly concentrated
      among the most deprived individuals leading to increasing socioeconomic
      inequalities in the incidence of cancers linked to smoking. We aimed to estimate
      the tobacco-attributable cancer burden according to socioeconomic position in
      France. The analysis was restricted to cancer sites for which tobacco smoking was
      recognized as a risk factor. Cancer cases by sex, age group and European
      Deprivation Index (EDI) among people aged 30-74 between 2006 and 2009 were
      obtained from cancer registries covering ~20% of the French population. The
      tobacco-attributable burden of cancer according to EDI was estimated applying the
      population attributable fraction (PAF) computed with the Peto-Lopez method. The
      PAF increased from 56% in the least deprived EDI quintile to 70% in the most
      deprived EDI quintile among men and from 26% to 38% among women. In total, 28% of
      the excess cancer cases in the four most deprived EDI quintiles in men and 43% in
      women could be prevented if smoking in these 4 EDI quintiles was similar to that
      of the least deprived EDI quintile. A substantial smoking-attributable burden of
      cancer by socioeconomic position was observed in France. The results highlight
      the need for policies reducing tobacco consumption. More comprehensive
      interventions integrating the various dimensions of health determinants and
      proportionate according to socioeconomic position may essentially contribute to
      the reduction of socioeconomic inequalities in cancer.

PMID- 29457850
TI  - Preparation, aroma characteristics and volatile compounds of flavorings from
      enzymatic hydrolyzed rice bran protein concentrate.
AB  - BACKGROUND: Rice bran is a by-product obtained from the rice milling industry.
      The aims of this research were to add value to rice bran by preparation of
      enzymatic hydrolyzed rice bran protein concentrate (HRPC) as a flavoring agent
      and the flavoring which was produced by HRPC has not been investigated. Different
      drying methods (freeze-drying and spray-drying) and fructose additions were
      studied for improvement of rice bran protein sensorial aroma characteristics.
      RESULTS: The most abundant amino acids in liquid HRPC (LH) were glutamic acid,
      arginine, aspartic acid and leucine. The intensity of desirable aromas, such as
      cereal-like, nut-like, milk-powder-like, sweet, and cocoa-like aroma, were higher
      in spray-dried HRPC powder (SHP) than in LH and freeze-dried HRPC. Volatile
      compounds, such as aldehydes, pyrazines and ketones, were significantly increased
      in HRPC powders in which fructose was added before spray-drying (SHP-F). Higher
      amounts of 2-methylbutanal, 3-methylbutanal, phenylacetaldehyde, 2,5
      dimethylpyrazine, vanillin, 2-acetylpyrrole and maltol were detected in SHP-F.
      Moreover, these compounds had high odor active values, which accounted for the
      cocoa-like, sweet, nut-like, and milk-powder-like characteristics of SHP-F.
      CONCLUSIONS: These findings could lead to the creation of desirable aroma
      characteristics of rice bran protein concentrate by different preparation
      methods. (c) 2018 Society of Chemical Industry.

PMID- 29457851
TI  - Suppression of microRNA-144-3p attenuates oxygen-glucose
      deprivation/reoxygenation-induced neuronal injury by promoting Brg1/Nrf2/ARE
      signaling.
AB  - Accumulating evidence has reported that microRNA-144-3p (miR-144-3p) is highly
      related to oxidative stress and apoptosis. However, little is known regarding its
      role in cerebral ischemia/reperfusion-induced neuronal injury. Herein, our
      results showed that miR-144-3p expression was significantly downregulated in
      neurons following oxygen-glucose deprivation and reoxygenation (OGD/R) treatment.
      Overexpression of miR-144-3p markedly reduced cell viability, promoted cell
      apoptosis, and increased oxidative stress in neurons with OGD/R treatment,
      whereas downregulation of miR-144-3p protected neurons against OGD/R-induced
      injury. Brahma-related gene 1 (Brg1) was identified as a potential target gene of
      miR-144-3p. Moreover, downregulation of miR-144-3p promoted the nuclear
      translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased
      antioxidant response element (ARE) activity. However, knockdown of Brg1
      significantly abrogated the neuroprotective effects of miR-144-3p downregulation.
      Overall, our results suggest that miR-144-3p contributes to OGD/R-induced
      neuronal injury in vitro through negatively regulating Brg1/Nrf2/ARE signaling.

PMID- 29457852
TI  - Successful management of living donor liver transplantation for biliary atresia
      with single ventricle physiology-from peri-transplant through total cavopulmonary
      connection: A case report.
AB  - Children with single ventricle physiology have complete mixing of the pulmonary
      and systemic circulations, requiring staged procedures to achieve a separation of
      these circulations, or Fontan circulation. The single ventricle physiology
      significantly increases the risk of mortality in children undergoing non-cardiac
      surgery. As liver transplantation for patients with single ventricle physiology
      is particularly challenging, only a few reports have been published. We herein
      report a case of successful LDLTx for an 8-month-old pediatric patient with
      biliary atresia, heterotaxy, and complex heart disease of single ventricle
      physiology. The cardiac anomalies included total anomalous pulmonary venous
      return type IIb, intermediate atrioventricular septal defect, tricuspid
      regurgitation grade III, coarctation of aorta, interrupted inferior vena cava,
      bilateral superior vena cava, and polysplenia syndrome. Following LDLTx, the
      patient sequentially underwent total cavopulmonary shunt + Damus-Kaye-Stansel at
      3 years of age and extracardiac total cavopulmonary connection (EC-TCPC)
      completion at 5 years of age; 7 years have now passed since LDLTx (2 years post
      EC-TCPC). We describe the details of the management of LTx in the presence of
      cardiac anomalies and report the long-term cardiac and liver function, from peri
      LDLTx through EC-TCPC completion.

PMID- 29457853
TI  - Mesenchymal-epithelial transition of pancreatic cancer cells at perineural
      invasion sites is induced by Schwann cells.
AB  - Epithelial-mesenchymal transition (EMT) promotes invasion and metastasis of
      pancreatic ductal adenocarcinoma (PDAC). However, the importance of its reverse
      process, mesenchymal-epithelial transition (MET), for PDAC remains unclear. We
      aimed to characterize the histological finding "focal differentiation" in PDAC at
      perineural invasion sites in the context of MET and to investigate the role of
      Schwann cells in inducing tumor MET. Tumor differentiation and
      immunohistochemical expressions of E-cadherin, SMAD3, and vimentin at perineural
      invasion sites were examined in 168 PDAC tissues. Four PDAC cell lines were co
      cultured with Schwann cells to investigate cell morphology, motility, or EMT
      related markers using immunocytochemistry and quantitative PCR. Of 168 tumors,
      124 (74%) showed focal differentiation with enhanced E-cadherin membrane
      expression (P < 0.001) and decreased nuclear accumulation of SMAD3 (P < 0.001).
      Among 115 PDACs harboring grade 1/2 tumor, tumors with focal differentiation
      showed worse survival compared to those without focal differentiation (P =
      0.019). PDAC cells co-cultured with Schwann cells demonstrated a sheet-like
      appearance, increased E-cadherin expression, decreased expressions of SMAD3 and
      vimentin, and reduced cell motility. In conclusion, MET-like change is induced by
      Schwann cells, suggesting that Schwann cells contribute to PDAC colonization in
      pancreatic nerves through activating the MET machinery inside tumor cells in the
      pancreatic tumor microenvironment.

PMID- 29457854
TI  - Metal Cluster Models for Heterogeneous Catalysis: A Matrix-Isolation Perspective.
AB  - Metal cluster models are of high relevance for establishing new mechanistic
      concepts for heterogeneous catalysis. The high reactivity and particular
      selectivity of metal clusters is caused by the wealth of low-lying electronically
      excited states that are often thermally populated. Thereby the metal clusters are
      flexible with regard to their electronic structure and can adjust their states to
      be appropriate for the reaction with a particular substrate. The matrix isolation
      technique is ideally suited for studying excited state reactivity. The low matrix
      temperatures (generally 4-40 K) of the noble gas matrix host guarantee that all
      clusters are in their electronic ground-state (with only a very few exceptions).
      Electronically excited states can then be selectively populated and their
      reactivity probed. Unfortunately, a systematic research in this direction has not
      been made up to date. The purpose of this review is to provide the grounds for a
      directed approach to understand cluster reactivity through matrix-isolation
      studies combined with quantum chemical calculations.

PMID- 29457855
TI  - Experimental study on TGF-beta1-mediated CD147 expression in oral submucous
      fibrosis.
AB  - OBJECTIVE: Although previous evidence indicates that CD147 is closely involved in
      the progression of organ fibrosis and various signaling pathways have been proven
      to regulate its expression, the role of CD147 in oral submucous fibrosis (OSF)
      remains largely unknown. METHODS: In this study, we investigated the expression
      of CD147 and transforming growth factor beta1 (TGF-beta1) in human samples of an
      OSF tissue array by immunohistopathology. Pearson's correlation analysis was
      conducted to explore the correlation between CD147 and TGF-beta1.
      Immunofluorescence and Western blotting were used to investigate to levels of
      CD147 in Human Oral Keratinocytes (HOKs) followed by TGF-beta1 or LY2157299, an
      inhibitor of TGF-beta1 receptor and arecoline stimulation. RESULTS: We found that
      CD147 was highly expressed in both HOKs and the fibrotic oral mucosa and that
      this expression was correlated with TGF-beta1 expression. Additionally, CD147
      levels were significantly associated with the fibrosis stage. The TGF-beta1
      signaling pathway was found to be mainly responsible for CD147 up-regulation
      after arecoline treatment whereas inhibition of TGF-beta1 down-regulated CD147
      expression. CONCLUSION: Our findings suggest arecoline promotes CD147 expression
      via the TGF-beta1 signaling pathway in HOKs, whereas overexpression of CD147 may
      promote OSF progression.

PMID- 29457856
TI  - Dual-Input Regulation and Positional Control in Hybrid Oligonucleotide/Discotic
      Supramolecular Wires.
AB  - The combination of oligonucleotides and synthetic supramolecular systems allows
      for novel and long-needed modes of regulation of the self-assembly of both
      molecular elements. Discotic molecules were conjugated with short
      oligonucleotides and their assembly into responsive supramolecular wires studied.
      The self-assembly of the discotic molecules provides additional stability for DNA
      duplex formation owing to a cooperative effect. The appended oligonucleotides
      allow for positional control of the discotic elements within the supramolecular
      wire. The programmed assembly of these hybrid architectures can be modulated
      through the DNA, for example, by changing the number of base pairs or salt
      concentration, and through the discotic platform by the addition of discotic
      elements without oligonucleotide handles. These hybrid supramolecular-DNA
      structures allow for advanced levels of control over 1D dynamic platforms with
      responsive regulatory elements at the interface with biological systems.

PMID- 29457857
TI  - Structural Studies of Self-Assembled Subviral Particles: Combining Cell-Free
      Expression with 110 kHz MAS NMR Spectroscopy.
AB  - Viral membrane proteins are prime targets in combatting infection. Still, the
      determination of their structure remains a challenge, both with respect to sample
      preparation and the need for structural methods allowing for analysis in a native
      like lipid environment. Cell-free protein synthesis and solid-state NMR
      spectroscopy are promising approaches in this context, the former with respect to
      its great potential in the native expression of complex proteins, and the latter
      for the analysis of membrane proteins in lipids. Herein, we show that milligram
      amounts of the small envelope protein of the duck hepatitis B virus (DHBV) can be
      produced by cell-free expression, and that the protein self-assembles into
      subviral particles. Proton-detected 2D NMR spectra recorded at a magic-angle
      spinning frequency of 110 kHz on <500 MUg protein show a number of isolated peaks
      with line widths comparable to those of model membrane proteins, paving the way
      for structural studies of this protein that is homologous to a potential drug
      target in HBV infection.

PMID- 29457858
TI  - Postsynthetic Functionalization of Three-Dimensional Covalent Organic Frameworks
      for Selective Extraction of Lanthanide Ions.
AB  - Chemical functionalization of covalent organic frameworks (COFs) is critical for
      tuning their properties and broadening their potential applications. However, the
      introduction of functional groups, especially to three-dimensional (3D) COFs,
      still remains largely unexplored. Reported here is a general strategy for
      generating a 3D carboxy-functionalized COF through postsynthetic modification of
      a hydroxy-functionalized COF, and for the first time exploration of the 3D
      carboxy-functionalized COF in the selective extraction of lanthanide ions. The
      obtained COF shows high crystallinity, good chemical stability, and large
      specific surface area. Furthermore, the carboxy-functionalized COF displays high
      metal loading capacities together with excellent adsorption selectivity for Nd3+
      over Sr2+ and Fe3+ as confirmed by the Langmuir adsorption isotherms and ideal
      adsorbed solution theory (IAST) calculations. This study not only provides a
      strategy for versatile functionalization of 3D COFs, but also opens a way to
      their use in environmentally related applications.

PMID- 29457859
TI  - Post-infectious acute glomerulonephritis with podocytopathy induced by parvovirus
      B19 infection.
AB  - Human parvovirus B19 infection causes a variety of glomerular diseases such as
      post-infectious acute glomerulonephritis and collapsing glomerulopathy. Although
      each of these appears independently, it has not been fully determined why
      parvovirus B19 provokes such a variety of different glomerular phenotypes. Here,
      we report a 68-year-old Japanese man who showed endocapillary proliferative
      glomerulonephritis admixed with podocytopathy in association with parvovirus B19
      infection. The patient showed acute onset of heavy proteinuria, microscopic
      hematuria and kidney dysfunction with arthralgia and oliguria after close contact
      with a person suffering from erythema infectiosum. In the kidney biopsy specimen,
      glomeruli revealed diffuse and global endocapillary infiltration of inflammatory
      cells, with some also showing tuft collapse with aberrant vacuolation, swelling,
      and hyperplasia of glomerular epithelial cells. Immunofluorescence revealed dense
      granular C3 deposition that resembled the "starry sky pattern". Intravenous
      glucocorticoid pulse therapy followed by oral prednisolone and cyclosporine
      combination therapy resulted in considerable amelioration of the kidney
      dysfunction and urinary abnormalities. The present case reveals that parvovirus
      B19 infection can induce different glomerular phenotypes even in the same kidney
      structure. This finding may provide hints useful for the further elucidation of
      the pathogenesis of parvovirus B19-induced glomerular lesions.

PMID- 29457860
TI  - Controlling the Outgrowth and Functions of Neural Stem Cells: The Effect of
      Surface Topography.
AB  - Neural stem cells (NSCs) are self-renewing cells that generate the major cell
      types of the central nervous system, namely neurons, astrocytes and
      oligodendrocytes, during embryonic development and in the adult brain. NSCs
      reside in a complex niche where they are exposed to a plethora of signals,
      including both soluble and physical signals such as compressive and shear
      stresses, but also discontinuities and differences in morphology of the
      extracellular environment, termed as topographical features. Different approaches
      that incorporate artificial micro- and nano-scale surface topographical features
      have been developed aiming to recapitulate the in vivo NSC niche discontinuities
      and features, particularly for in vitro studies. The present review article aims
      at reviewing the existing body of literature on the use of artificial micro- and
      nano-topographical features to control NSCs orientation and differentiation into
      neuronal and/or neuroglial lineage. The different approaches on the study of the
      underlying mechanism of the topography-guided NSC responses are additionally
      revised and discussed.

PMID- 29457861
TI  - Promoted Fixation of Molecular Nitrogen with Surface Oxygen Vacancies on Plasmon
      Enhanced TiO2 Photoelectrodes.
AB  - A hundred years on, the energy-intensive Haber-Bosch process continues to turn
      the N2 in air into fertilizer, nourishing billions of people while causing
      pollution and greenhouse gas emissions. The urgency of mitigating climate change
      motivates society to progress toward a more sustainable method for fixing N2 that
      is based on clean energy. Surface oxygen vacancies (surface Ovac ) hold great
      potential for N2 adsorption and activation, but introducing Ovac on the very
      surface without affecting bulk properties remains a great challenge. Fine tuning
      of the surface Ovac by atomic layer deposition is described, forming a thin
      amorphous TiO2 layer on plasmon-enhanced rutile TiO2 /Au nanorods. Surface Ovac
      in the outer amorphous TiO2 thin layer promote the adsorption and activation of
      N2 , which facilitates N2 reduction to ammonia by excited electrons from
      ultraviolet-light-driven TiO2 and visible-light-driven Au surface plasmons. The
      findings offer a new approach to N2 photofixation under ambient conditions (that
      is, room temperature and atmospheric pressure).

PMID- 29457862
TI  - Peter J. Dunn Award: B. H. Lipshutz and S. Handa / International Solvay Chair in
      Chemistry: G. Frenking / Max Born Prize: A. Rubio / Terrae Rarae Prize: R. Kempe
      / Frontiers in Chemical Energy Science Award: K. Reuter / New Members of the
      Academia Europaea.

PMID- 29457863
TI  - The B-type natriuretic peptide is a useful biomarker for the estimation of volume
      overload in children with hypertension in children on peritoneal dialysis.
AB  - AIM: To evaluate the usefulness of serum B-type natriuretic peptide (BNP) as a
      biomarker of fluid retention in hypertensive children on peritoneal dialysis
      (PD). METHODS: We included hypertensive children on PD. We reviewed the changes
      (?) of body weight (BWt), blood pressure (BP) and serum BNP at initial and follow
      up periods. We presented data as mean+/-standard deviation (median, minimum -
      maximum). Wilcoxon signed-rank test was used to evaluate the changes in BWt, BP,
      and BNP. We applied linear regression analysis for the correlation between the
      changes of BNP and BP. RESULTS: We evaluated 56 hypertensive events in 30
      patients. Initial findings were BWt 30.5+/-22.4 (26.5, 3.0 - 93.5) kg, systolic
      BP (SBP) 153.3+/-21.5 (150, 110 - 241) mmHg, diastolic BP (DBP) 100.1+/-22.3,
      (99.5, 49 - 181) mmHg, BNP 3579.3+/-6328.9 (1198.5, 305 - 22028) pg/mL. Follow-up
      results were BWt 29.1+/-21.3 (25.0, 3.12 - 86) kg, SBP 116.4+/-17.8 (117.5, 82 -
      150) mmHg, DBP 73.3+/-14.2 (75.0, 42.0 - 101.0) mmHg, BNP 63.5+/-49.2 (60.5, 2 -
      261) pg/mL. ?SBP (-23.1+/-13.8, -22.8, -46.9 - 22.5%, P<0.001), ?DBP (-24.1+/
      19.2, -24.7, -55.6 - 23.2%, P<0.001) and ?BNP (-93.5+/-8.1, -96.7, -99.9 - 
      61.0%, P<0.001) dropped significantly after reduction of ?BWt (-4.8+/-4.7, -4.8, 
      18.7 - 5.6%, P<0.001). The ?BNP were significantly correlated with ?SBP (adjusted
      R square = 0.221, P<0.001) and ?DBP ( adjusted R square = 0.203, P < 0.001).
      CONCLUSIONS: We should measure BNP in hypertensive patients on PD to evaluate the
      volume status.

PMID- 29457864
TI  - Promotion of a Reaction by Cooling: Stereoselective 1,2-cis-alpha
      Thioglycoconjugation by Thiol-Ene Coupling at -80  degrees C.
AB  - The photoinitiated thiol-ene coupling reactions of 2-substituted glycals were
      studied as a generally applicable strategy for stereoselective 1,2-cis-alpha
      thioconjugation. Although all glycals reacted with full alpha-selectivity, the
      efficacy of the reactions varied in a broad range depending on their
      configuration and glycals bearing axial acetoxy substituents reacted with very
      low efficacy at room temperature. The study revealed that the reaction progress
      could be promoted by cooling and inhibited by heating. At -80  degrees C, the
      equilibrium of the rapidly reversible addition of the thiyl radical to alkenes is
      shifted almost completely toward products, leading to efficient addition
      reactions. By exploiting this unique temperature effect a series of alpha-thio-l
      fucosides, -d-galactosides, and d-GlcNAc derivatives were prepared with high
      efficacy and complete stereoselectivity.

PMID- 29457866
TI  - Epigenetic effects of metformin: From molecular mechanisms to clinical
      implications.
AB  - There is a growing body of evidence that links epigenetic modifications to type 2
      diabetes. Researchers have more recently investigated effects of commonly used
      medications, including those prescribed for diabetes, on epigenetic processes.
      This work reviews the influence of the widely used antidiabetic drug metformin on
      epigenomics, microRNA levels and subsequent gene expression, and potential
      clinical implications. Metformin may influence the activity of numerous
      epigenetic modifying enzymes, mostly by modulating the activation of AMP
      activated protein kinase (AMPK). Activated AMPK can phosphorylate numerous
      substrates, including epigenetic enzymes such as histone acetyltransferases
      (HATs), class II histone deacetylases (HDACs) and DNA methyltransferases (DNMTs),
      usually resulting in their inhibition; however, HAT1 activity may be increased.
      Metformin has also been reported to decrease expression of multiple histone
      methyltransferases, to increase the activity of the class III HDAC SIRT1 and to
      decrease the influence of DNMT inhibitors. There is evidence that these
      alterations influence the epigenome and gene expression, and may contribute to
      the antidiabetic properties of metformin and, potentially, may protect against
      cancer, cardiovascular disease, cognitive decline and aging. The expression
      levels of numerous microRNAs are also reportedly influenced by metformin
      treatment and may confer antidiabetic and anticancer activities. However, as the
      reported effects of metformin on epigenetic enzymes act to both increase and
      decrease histone acetylation, histone and DNA methylation, and gene expression, a
      significant degree of uncertainty exists concerning the overall effect of
      metformin on the epigenome, on gene expression, and on the subsequent effect on
      the health of metformin users.

PMID- 29457865
TI  - Nucleophilic Substitution in Solution: Activation Strain Analysis of Weak and
      Strong Solvent Effects.
AB  - We have quantum chemically studied the effect of various polar and apolar
      solvents on the shape of the potential energy surface (PES) of a diverse
      collection of archetypal nucleophilic substitution reactions at carbon, silicon,
      phosphorus, and arsenic by using density functional theory at the OLYP/TZ2P
      level. In the gas phase, all our model SN 2 reactions have single-well PESs,
      except for the nucleophilic substitution reaction at carbon (SN 2@C), which has a
      double-well energy profile. The presence of the solvent can have a significant
      effect on the shape of the PES and, thus, on the nature of the SN 2 process.
      Solvation energies, charges on the nucleophile or leaving group, and structural
      features are compared for the various SN 2 reactions in a spectrum of solvents.
      We demonstrate how solvation can change the shape of the PES, depending not only
      on the polarity of the solvent, but also on how the charge is distributed over
      the interacting molecular moieties during different stages of the reaction. In
      the case of a nucleophilic substitution at three-coordinate phosphorus, the
      reaction can be made to proceed through a single-well [no transition state (TS)],
      bimodal barrier (two TSs), and then through a unimodal transition state (one TS)
      simply by increasing the polarity of the solvent.

PMID- 29457867
TI  - Comparative toxicity studies on bromochloroacetate, dibromoacetate, and
      bromodichloroacetate in J774A.1 macrophages: Roles of superoxide anion and
      protein carbonyl compounds.
AB  - The brominated and mixed bromo-chloro-haloacetates, such as dibromoacetate (DBA),
      bromochloroacetate (BCA), and bromodichloroacetate (BDCA), are by-products of
      water chlorination and are found at lower levels than the fully chlorinated
      acetates in the drinking water. The toxicities of the compounds were assessed in
      J774A.1 cells and were found to induce concentration-dependent increases in cell
      death and superoxide anion and protein carbonyl compounds production. Compared to
      the previously tested concentrations of dichoroacetate (DCA) and trichloroacetate
      (TCA) in the same cell line, the tested haloacetates induced similar effects on
      cellular viability and superoxide anion production but at DBA and BCA
      concentrations that were approximately 40-160 times lower than those of DCA and
      TCA, and at BDCA concentrations that were 4-16 times lower than those of DCA and
      TCA. Also, production of super oxide anion, protein carbonyl compounds, and
      induction of phagocytic activation are suggested to play a role in their
      toxicity.

PMID- 29457868
TI  - Exploring acceptability of oral PrEP prior to implementation among female sex
      workers in South Africa.
AB  - INTRODUCTION: Female sex workers (FSWs) are at high-risk for HIV acquisition in
      South Africa, where the advent of new HIV prevention and treatment interventions
      represent the potential to significantly impact the epidemic. This paper focuses
      on aspects of PrEP acceptability as a new intervention within the context of a
      larger service delivery programme including the simultaneous rollout of early
      ART. This paper explores PrEP acceptability among the FGD participants as future
      potential users. METHODS: FGDs were conducted in two clinic-based sites in
      Johannesburg and Pretoria. They aimed to explore community-level, multi
      dimensional acceptability of PrEP within the context of imminent implementation
      alongside early ART in the TAPS Demonstration Project. Sex worker peer educators
      recruited participants from varying sex work locales. Facilitation was in English
      with adaptation by facilitators into local languages as needed. Transcripts were
      translated and transcribed into English. Thematic analysis was used to analyse
      the data. RESULTS: Four FGDs were conducted in each site for a total of eight
      FDGs and 69 participants. Demographics were largely similar across the sites.
      Overall, there was strong acceptability of PrEP among participants and positive
      anticipation for the imminent delivery of PrEP in the local sex worker clinics.
      Themes arising from the discussions exploring aspects of PrEP acceptability
      included: awareness and understanding of PrEP; PrEP motivations including choice,
      control, and vulnerability, managing PrEP risks and worries; and, de-stigmatizing
      and empowering PrEP delivery. Participant discussions and recommendations
      highlighted the importance of developing clear education and messaging to
      accurately convey the concept of PrEP, and intervention integration into
      supportive and tailored services. CONCLUSIONS: Through the course of these FGDs,
      PrEP became a positive and highly anticipated prevention option among the FSWs
      participants who endorsed implementation in their communities. Effective
      integration of PrEP into existing services will include comprehensive health
      programming where ART is also available, appropriate messaging, and support.

PMID- 29457870
TI  - Effect of the flow profile on separation efficiency in pressure-assisted reversed
      polarity capillary zone electrophoresis of anions: Simulation and experimental
      evaluation.
AB  - Capillary electrophoresis connected to electrospray ionization mass spectrometry
      is a promising combination to analyze complex biological samples. The use of
      sheathless electrospray ionization interfaces, such as a porous nanoelectrospray
      capillary emitter, requires the application of forward flow (either by pressure
      or electroosmosis) to maintain the electrospray process. The analysis of solute
      molecules with strong negative charges (e.g., aminopyrenetrisulfonate labeled
      glycans) necessitates a reversed-polarity capillary electrophoresis separation
      mode, in which case the electroosmotic flow is counter current, thus pressure
      assistance is necessary. In this study, we compared the effect of forced
      convection with and without counter electroosmotic flow on the resulting
      separation efficiency in capillary electrophoresis based on flow profile
      simulations by computational fluid dynamics technique and by actual experiments.
      The efficiencies of the detected peaks were calculated from the resulting
      electropherograms and found approximately 950 000 plates/m for electrophoresis
      with counter electroosmotic flow, 20 000 plates/m with pressure only (such as
      would be in open tubular liquid chromatography), and 480 000 plates/m for
      electrophoresis with simultaneous counter electroosmotic flow and forward
      pressure assistance, which validates the simulation data.

PMID- 29457869
TI  - Assessment of the spectrum of hepatic encephalopathy: A multicenter study.
AB  - Hepatic encephalopathy (HE) is a major cause of morbidity in cirrhosis. However,
      its severity assessment is often subjective, which needs to be studied
      systematically. The aim was to determine how accurately trainee and nontrainee
      practitioners grade and manage HE patients throughout its severity. We performed
      a survey study using standardized simulated patient videos at 4 US and 3 Canadian
      centers. Participants were trainees (gastroenterology/hepatology fellows) and
      nontrainees (faculty, nurse practitioners, physician assistants). We determined
      the accuracy of HE severity identification and management options between grades
      <2 or >=2 HE and trainees/nontrainees. In total, 108 respondents (62 trainees, 46
      nontrainees) were included. For patients with grades <2 versus >=2 HE, a higher
      percentage of respondents were better at correctly diagnosing grades >=2 compared
      with grades <2 (91% versus 64%; P < 0.001). Specialized cognitive testing was
      checked significantly more often in grades <2, whereas more aggressive
      investigation for precipitating factors was ordered in HE grades >2. Serum
      ammonia levels were ordered in almost a third of grade >=2 patients. For trainees
      and nontrainees, HE grades were identified similarly between groups. Trainees
      were less likely to order serum ammonia and low-protein diets, more likely to
      order rifaximin, and more likely to perform a more thorough workup for
      precipitating factors compared with nontrainee respondents. There was excellent
      concordance in the classification of grade >=2 HE between nontrainees versus
      trainees, but lower grades showed discordance. Important differences were seen
      regarding blood ammonia, specialized testing, and nutritional management between
      trainees and nontrainees. These results have important implications at the
      patient level, interpreting multicenter clinical trials, and in the education of
      practitioners. Liver Transplantation 24 587-594 2018 AASLD.

PMID- 29457871
TI  - A quantitative trait locus on chromosome 1 modulates intermale aggression in
      mice.
AB  - Aggression between male conspecifics is a complex social behavior that is likely
      modulated by multiple gene variants. In this study, the BXD recombinant inbred
      mouse strains (RIS) were used to map quantitative trait loci (QTLs) underlying
      behaviors associated with intermale aggression. Four hundred and fifty-seven
      males from 55 strains (including the parentals) were observed at an age of 13 +/-
      1 week in a resident-intruder test following 10 days of isolation. Attack latency
      was measured directly within a 10-minute time period and the test was repeated 24
      hours later. The variables we analyzed were the proportion of attacking males in
      a given strain as well as the attack latency (on days 1 and 2, and both days
      combined). On day 1, 29% of males attacked, and this increased to 37% on day 2.
      Large strain differences were obtained for all measures of aggression, indicating
      substantial heritability (intraclass correlations 0.10-0.18). We identified a
      significant QTL on chromosome (Chr) 1 and suggestive QTLs on mouse Chrs 1 and 12
      for both attack and latency variables. The significant Chr 1 locus maps to a gene
      sparse region between 82 and 88.5 Mb with the C57BL/6J allele increasing
      aggression and explaining about 18% of the variance. The most likely candidate
      gene modulating this trait is Htr2b which encodes the serotonin 2B receptor and
      has been implicated in aggressive and impulsive behavior in mice, humans and
      other species.

PMID- 29457872
TI  - Simple method for the determination of personal care product ingredients in
      lettuce by ultrasound-assisted extraction combined with solid-phase
      microextraction followed by GC-MS.
AB  - A simple method for the simultaneous determination of personal care product
      ingredients: galaxolide, tonalide, oxybenzone, 4-methylbenzyliden camphor,
      padimate-o, 2-ethylhexyl methoxycinnamate, octocrylene, triclosan, and methyl
      triclosan in lettuce by ultrasound-assisted extraction combined with solid-phase
      microextraction followed by gas chromatography with mass spectrometry was
      developed. Lettuce was directly extracted by ultrasound-assisted extraction with
      methanol, this extract was combined with water, extracted by solid-phase
      microextraction in immersion mode, and analyzed by gas chromatography with mass
      spectrometry. Good linear relationships (25-250 ng/g, R2  > 0.9702) and low
      detection limits (1.0-25 ng/g) were obtained for analytes along with acceptable
      precision for almost all analytes (RSDs < 20%). The validated method was applied
      for the determination of personal care product ingredients in commercial lettuce
      and lettuces grown in soil and irrigated with the analytes, identifying the
      target analytes in leaves and roots of the latter. This procedure is a
      miniaturized and environmentally friendly proposal which can be a useful tool for
      quality analysis in lettuce.

PMID- 29457873
TI  - The impact of video nasal endoscopy on patient satisfaction.
AB  - BACKGROUND: Video nasal endoscopy has significant associated expense for
      practices, but its use has been justified by the benefit it provides to the
      examiner. No study has examined the perceived benefit to the patient. In this
      study, the impact of video endoscopy on patient satisfaction is evaluated.
      METHODS: A prospective, randomized, single-blinded study was performed on new
      patients receiving care in the rhinology clinics of a tertiary-care center.
      Patients were randomized into the standard endoscopic examination (SEE) or video
      endoscopic examination (VEE) groups. SEE patients had their examination performed
      with the physician viewing the exam through the eyepiece, without a video camera,
      and subsequently had their examination explained. VEE patients had their
      examination performed with a video camera attached to the scope, recorded, and
      then used for the explanation. All patients were asked to complete the 22-item
      Sino-Nasal Outcome Test (SNOT-22) and the 18-item Patient Satisfaction
      Questionnaire Short-Form (PSQ-18). Statistical analysis was performed to identify
      differences between cohorts. RESULTS: There was no significant demographic
      difference between groups. SNOT-22 total and domain scores were similar between
      both groups (p > 0.05). VEE patients had significantly higher general
      satisfaction (p = 0.048) and communication (p = 0.028) domains within the PSQ-18.
      There was no difference between other domains (p > 0.05). CONCLUSION: VEE is a
      valuable tool for otolaryngologists and patients. Further studies evaluating
      variance in patient compliance and symptomatology may provide further
      justification for its use.

PMID- 29457874
TI  - Computed tomography analysis of frontal cell prevalence according to the
      International Frontal Sinus Anatomy Classification.
AB  - BACKGROUND: The International Frontal Sinus Anatomy Classification (IFAC) is an
      international consensus document published in 2016 to standardize the
      nomenclature of cells in the region of the frontal recess and frontal sinus. The
      IFAC was designed to be surgically relevant and anatomically precise. The current
      study was undertaken to assess the prevalence of the frontal cell variants as
      defined by the IFAC, as well as to determine the interrater reliability of the
      IFAC. METHODS: Three independent reviewers examined triplanar nondiseased
      maxillofacial computed tomography (CT) scans to assess the anatomy of the frontal
      recess according to the IFAC system. The prevalence of each cell type was
      assessed and interrater reliability was measured using an intraclass correlation
      coefficient (ICC). RESULTS: One hundred CT scans (200 sides) were examined. Of
      the 200 sides, 96.5% contained an agger nasi cell (ICC, 0.82; 95% confidence
      interval [CI], 0.77-0.86), 30.0% contained a supra agger cell (ICC, 0.89; 95% CI,
      0.86-0.92), 20.0% contained a supra agger frontal cell (ICC 0.80; 95% CI 0.74
      0.84), 72.0% contained a supra bulla cell (ICC, 0.81; 95% CI, 0.76-0.85), 5.5%
      contained a supra bulla frontal cell (ICC, 0.71; 95% CI, 0.63-0.77), 28.5%
      contained a supraorbital ethmoid cell (ICC, 0.78; 95% CI, 0.72-0.83), and 30.0%
      contained a frontal septal cell (ICC, 0.80; 95% CI, 0.74-0.84). The ICC was good
      to excellent for identification of all frontal cell types. CONCLUSIONS: This
      study describes the normative distribution of frontal recess cells in a
      nondiseased population according to IFAC and demonstrates favorable interrater
      reliability of the classification system.

PMID- 29457875
TI  - Variations of the Circle of Willis at the End of the Human Embryonic Period.
AB  - Variations of the circle of Willis (CW) influence blood supply to the brain and
      adjacent structures in adults. We examined the formation of the CW in 20 human
      embryo samples at the end of the embryonic period using 3-D reconstructions of
      serial histological sections. The CW was closed in all samples, and did not form
      in a single plane, but was composed of multiple stair-like planes. The artery
      acutely curved at the caudal part of the CW, namely, at the inlet of the basilar
      artery and bifurcation of the P1 segment of the posterior cerebral artery (PCA),
      reflecting flexure of the mesencephalon and diencephalon at this stage.
      Variations were observed in 17 of 20 samples-only anterior parts (anterior
      communicating artery [Acom] and anterior cerebral artery [ACA]) in 10 samples,
      only posterior parts (posterior communicating artery [Pcom]) in one sample, and
      both anterior and posterior parts in six samples. Variations included the Acom
      formed as partially duplicated in three samples, duplicated in four, plexiform in
      three, and no channel as a result of a single azygos ACA in one. The ACA formed
      as duplicated in two, median ACA in two, and right hypoplasia in one. The Pcom
      formed in hypoplasia of either side in six samples. Variations observed in this
      study are similar to those observed in fetuses, neonates, and adults. The P1
      segment of PCA was very large in all samples. The present observations indicate
      that variations in the CW are present from the initiation of CW formation. Anat
      Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29457876
TI  - Pharmacokinetics of metformin in patients with gastrointestinal intolerance.
AB  - AIMS: To assess potential causes of metformin intolerance, including altered
      metformin uptake from the intestine, increased anaerobic glucose utilization and
      subsequent lactate production, altered serotonin uptake, and altered bile acid
      pool. METHODS: For this pharmacokinetic study, we recruited 10 severely
      intolerant and 10 tolerant individuals, matched for age, sex and body mass index.
      A single 500-mg dose of metformin was administered, with blood sampling at 12
      time points over 24 hours. Blood samples were analysed for metformin, lactate,
      serotonin and bile acid concentrations, and compared across the phenotypes.
      RESULTS: The intolerant individuals were severely intolerant to 500 mg metformin.
      No significant difference was identified between tolerant and intolerant cohorts
      in metformin pharmacokinetics: median (interquartile range [IQR]) peak
      concentration 2.1 (1.7-2.3) mg/L and 2.0 (1.8-2.2) mg/L, respectively (P = .76);
      time to peak concentration 2.5 hours; median (IQR) area under the curve (AUC)0-24
      16.9 (13.9-18.6) and 13.9 (12.9-16.8) mg/L*h, respectively (P = .72). Lactate
      concentration peaked at 3.5 hours, with mean peak concentration of 2.4 mmol/L in
      both cohorts (95% CI 2.0-2.8 and 1.8-3.0 mmol/L, respectively), and similar
      incremental AUC0-24 in each cohort: tolerant cohort 6.98 (95% CI 3.03-10.93) and
      intolerant cohort 4.47 (95% CI -3.12-12.06) mmol/L*h (P = .55). Neither serotonin
      nor bile acid concentrations were significantly different. CONCLUSIONS: Despite
      evidence of severe intolerance in our cohort, there was no significant difference
      in metformin pharmacokinetics or systemic measures of lactate, serotonin or bile
      acids. This suggests that metformin intolerance may be attributable to local
      factors within the lumen or enterocyte.

PMID- 29457878
TI  - Genetic determinants of heart failure: facts and numbers.
AB  - The relevance of gene mutations leading to heart diseases and hence heart failure
      has become evident. The risk for and the course of heart failure depends on
      genomic variants and mutations underlying the so-called genetic predisposition.
      Genetic contribution to heart failure is highly heterogenous and complex. For any
      patient with a likely inherited heart failure syndrome, genetic counselling is
      recommended and important. In the last few years, novel sequencing technologies
      (named next-generation sequencing - NGS) have dramatically improved the
      availability of molecular testing, the efficiency of genetic analyses, and
      moreover reduced the cost for genetic testing. Due to this development, genetic
      testing has become increasingly accessible and NGS-based sequencing is now
      applied in clinical routine diagnostics. One of the most common reasons of heart
      failure are cardiomyopathies such as the dilated or the hypertrophic
      cardiomyopathy. Nearly 100 disease-associated genes have been identified for
      cardiomyopathies. The knowledge of a pathogenic mutation can be used for genetic
      counselling, risk and prognosis determination, therapy guidance and hence for a
      more effective treatment. Besides, family cascade screening for a known familial,
      pathogenic mutation can lead to an early diagnosis in affected individuals. At
      that timepoint, a preventative intervention could be used to avoid or delay
      disease onset or delay disease progression. Understanding the cellular basis of
      genetic heart failure syndromes in more detail may provide new insights into the
      molecular biology of physiological and impaired cardiac (cell) function. As our
      understanding of the molecular and genetic pathophysiology of heart failure will
      increase, this might help to identify novel therapeutic targets and may lead to
      the development of new and specific treatment options in patients with heart
      failure.

PMID- 29457879
TI  - The good, the bad, and the ugly of luminex donor-specific crossmatch.
AB  - The presence of donor-specific antibodies directed against human leukocyte
      antigen significantly influences renal transplant because of antibody-mediated
      rejection. We performed the screening of pre-renal transplant patients for
      preformed anti-HLA antibodies using anti-human globulin augmented-complement
      dependent lymphocytotoxicity crossmatch (AHG-CDCXm), luminex donor-specific
      crossmatch (LumXm) and HLA antibody screening. Seven hundred and fifty-four
      patients were assessed for LumXm. HLA antibody screening was possible in 325 out
      of 754 cases. All the three investigations viz. CDCXm, HLA antibody screening and
      LumXm was performed in 325 patients. All CDCXm positive patients (10/325, 3.08%)
      were also positive with LumXm and HLA antibody screen whereas 14 cases (4.31%)
      with CDCXm negative were positive with luminex-based assays. LumXm and HLA
      antibody screening were both positive in 24 (7.38%) cases, LumXm and HLA antibody
      screening were both negative in 275 (84.63%) cases and LumXm negative and HLA
      antibody screening was positive in 22 (6.76%) cases. However, there were four
      cases (1.23%) which were positive in LumXm in spite of being negative in HLA
      antibody testing. Single Antigen Bead (SAB) assay was performed in all patients
      positive for HLA antibody test. We suggest that LumXm is a useful and sensitive
      technique for the detection of anti-HLA antibodies in pre-transplant renal
      patients. However, other measures such as luminex antibody screen, SAB assay,
      history of the donor, and the class of antibodies involved should be taken into
      consideration for pre-transplant work up of renal patients.

PMID- 29457880
TI  - Higher retransplantation rate following extended right split-liver
      transplantation: An analysis from the eurotransplant liver follow-up registry.

PMID- 29457877
TI  - Atrial remodelling in heart failure: recent developments and relevance for heart
      failure with preserved ejection fraction.

PMID- 29457881
TI  - Cesarean section.

PMID- 29457882
TI  - Unregulated Drinking Water Systems.
AB  - (1)One in 9 Americans gets his or her drinking water from a private well. (2) An
      estimated 20 percent of private wells have contaminants above Environmental
      Protection Agency drinking water standards.(3) Disease outbreaks from private
      wells are increasing, according to the Centers forDisease Control and Prevention.

PMID- 29457883
TI  - Mapping the H-NOX/HK Binding Interface in Vibrio cholerae by Hydrogen/Deuterium
      Exchange Mass Spectrometry.
AB  - Heme-nitric oxide/oxygen binding (H-NOX) proteins are a group of hemoproteins
      that bind diatomic gas ligands such as nitric oxide (NO) and oxygen (O2). H-NOX
      proteins typically regulate histidine kinases (HK) located within the same
      operon. It has been reported that NO-bound H-NOXs inhibit cognate histidine
      kinase autophosphorylation in bacterial H-NOX/HK complexes; however, a detailed
      mechanism of NO-mediated regulation of the H-NOX/HK activity remains unknown. In
      this study, the binding interface of Vibrio cholerae ( Vc) H-NOX/HK complex was
      characterized by hydrogen/deuterium exchange mass spectrometry (HDX-MS) and
      further validated by mutagenesis, leading to a new model for NO-dependent kinase
      inhibition. A conformational change in Vc H-NOX introduced by NO generates a new
      kinase-binding interface, thus locking the kinase in an inhibitory conformation.

PMID- 29457884
TI  - Unique Biochemical and Sequence Features Enable BluB To Destroy Flavin and
      Distinguish BluB from the Flavin Monooxygenase Superfamily.
AB  - Vitamin B12 (cobalamin) is an essential micronutrient for humans that is
      synthesized by only a subset of bacteria and archaea. The aerobic biosynthesis of
      5,6-dimethylbenzimidazole, the lower axial ligand of cobalamin, is catalyzed by
      the "flavin destructase" enzyme BluB, which fragments reduced flavin
      mononucleotide following its reaction with oxygen to yield this ligand. BluB is
      similar in sequence and structure to members of the flavin oxidoreductase
      superfamily, yet the flavin destruction process has remained elusive. Using
      stopped-flow spectrophotometry, we find that the flavin destructase reaction of
      BluB from Sinorhizobium meliloti is initiated with canonical flavin-O2 chemistry.
      A C4a-peroxyflavin intermediate is rapidly formed in BluB upon reaction with O2,
      and has properties similar to those of flavin-dependent hydroxylases. Analysis of
      reaction mixtures containing flavin analogues indicates that both formation of
      the C4a-peroxyflavin and the subsequent destruction of the flavin to form 5,6
      dimethylbenzimidazole are influenced by the electronic properties of the flavin
      isoalloxazine ring. The flavin destruction phase of the reaction, which results
      from the decay of the C4a-peroxyflavin intermediate, occurs more efficiently at
      pH >7.5. Furthermore, the BluB mutants D32N and S167G are specifically impaired
      in the flavin destruction phase of the reaction; nevertheless, both form the C4a
      peroxyflavin nearly quantitatively. Coupled with a phylogenetic analysis of BluB
      and related flavin-dependent enzymes, these results demonstrate that the BluB
      flavin destructase family can be identified by the presence of active site
      residues D32 and S167.

PMID- 29457885
TI  - Thienyl-Substituted alpha-Ketoamide: A Less Hydrophobic Reactive Group for Photo
      Affinity Labeling.
AB  - Photoaffinity labeling (PAL) is an important tool in chemical biology research,
      but application of alpha-ketoamides for PAL has been hampered by their
      photoinstability. Here, we show that 2-thienyl-substituted alpha-ketoamide is a
      superior photoreactive group for PAL. Studies with a series of synthetic mannose
      conjugated alpha-ketoamides revealed that 2-thienyl substitution of alpha
      ketoamide decreased the electrophilicity of the keto group and reduced the rate
      of photodegradation. Mannose-conjugated thienyl alpha-ketoamide showed greater
      concanavalin A labeling efficiency than other alkyl or phenyl-substituted alpha
      ketoamides. In comparison with representative conventional photoreactive groups,
      2-thienyl ketoamide showed reduced labeling of nontarget proteins, probably owing
      to its lower hydrophobicity.

PMID- 29457886
TI  - Janus Gradient Meshes for Continuous Separation and Collection of Flowing Oils
      under Water.
AB  - Gradient meshes with Janus wettabilities are fabricated to stably separate and
      collect spilled oils from a range of flowing oily wastewater. Here, we
      demonstrate an overflow with separation methodology, which combines selective oil
      overflow and membrane separation, to separate low content oils from dynamic
      flowing oil-water mixtures by a curved gradient mesh that covered on a solid
      edge. The microscaled air-oil-water-solid four-phase wetting state during the oil
      water separation process is visualized and demonstrated. The fundamental
      understanding of this overflow with separation system and the superior gradient
      mesh materials would enable us to construct a wide variety of separation devices
      out of traditional designs and advance related applications, such as wastewater
      treatment and fuel purification.

PMID- 29457888
TI  - Potential Therapeutic Applications for Inhibitors of Autotaxin, a Bioactive Lipid
      Producing Lysophospholipase D, in Disorders Affecting the Nervous System.
AB  - Autotaxin is a dual-function ecto-enzyme, encoded by the gene ENPP2, which is the
      primary source of the bioactive signaling lipid, lysophosphatidic acid.
      Aberrations in autotaxin/lysophosphatidic acid signaling have been associated
      with a number of neurological, psychiatric, neoplastic, and neurodevelopmental
      conditions, such as pain, pruritus, glioblastoma multiforme, multiple sclerosis,
      Alzheimer's disease, hydrocephalus, and schizophrenia. This Viewpoint offers a
      brief overview of the likely indications for therapeutic targeting of autotaxin,
      in disorders affecting the nervous system.

PMID- 29457887
TI  - Synthesis of Highly Substituted Imidazole Uracil Containing Molecules via Ugi-4CR
      and Passerini-3CR.
AB  - The synthesis of uracil/thymine containing tetra/trisubstituted imidazole
      derivatives was demonstrated using Ugi/Passerini-reaction followed by a
      postcyclization reaction sequence. The approach enables the one-pot facile
      construction of diverse compounds in moderate to excellent yields (47-82%). The 5
      fluorouracil and 5-methyluracil moieties afford potentially bioactive molecules
      with drug-like properties. These scaffolds are currently being utilized in the
      screening deck of the European Lead Factory.

PMID- 29457889
TI  - Rapid Microwave Preparation and Composition Tuning of the High-Performance
      Magnetocalorics (Mn,Fe)2(P,Si).
AB  - Rapid preparation utilizing assisted microwave heating permits significantly
      shorter preparation times for magnetocaloric compounds in the (Mn,Fe)2(P,Si)
      family, specifically samples of (Mn,Fe)2-deltaP0.5Si0.5 with starting
      compositions of delta = 0, 0.06, and 0.12. To fully understand the effects of
      processing and composition changes on structure and properties, these materials
      are characterized using synchrotron powder diffraction, neutron powder
      diffraction, electron microprobe analysis (EMPA), X-ray fluorescence (XRF), and
      magnetic measurements. The diffraction analysis reveals that increasing delta
      results in decreasing amounts of the common Heusler (Mn,Fe)3Si secondary phase.
      EMPA shows (Mn,Fe)2(P,Si) in all three samples to be Mn and P rich, whereas XRF
      demonstrates that the bulk material is Mn rich yet P deficient. Increasing delta
      brings the Mn/Fe and P/Si ratios closer to their starting values. Measurements of
      magnetic properties show an increase in saturation magnetization and ordering
      temperature with increasing delta, consistent with the increase in Fe and Si
      contents. Increasing delta also results in a decrease in thermal hysteresis and
      an increase in magnetic entropy change, the latter reaching values close to what
      have been previously reported on samples that take much longer to prepare.

PMID- 29457890
TI  - Headspace Solid-Phase Microextraction Coupled to Miniaturized Microplasma Optical
      Emission Spectrometry for Detection of Mercury and Lead.
AB  - Despite increased interest in microplasma atomic spectrometry over the past
      several years, its applications to field analysis of real samples still remain
      limited due to its low sensitivity. In this work, headspace solid-phase
      microextraction (HS-SPME) using PDMS/DVB fiber was used as a sample introduction
      method to improve the sensitivity of a miniature (6.0 cm length * 5.0 cm width *
      2.8 cm height) low power (<10 W) microplasma point discharge optical emission
      spectrometer (PD-OES) for the determination of Hg and Pb after their
      derivatization with sodium tetraethylborate (NaBEt4). Owing to its advantages of
      combining sampling, separation, and preconcentration of analytes from sample
      matrices into a single step, HS-SPME not only simplifies sample pretreatment and
      the experimental setup but also eliminates interferences from matrices and water
      vapor while significantly improving analytical performance. In comparison to
      photochemical vapor generation PD-OES, limits of detection for Hg and Pb were
      enhanced by at least 100-fold, providing great potential for field analysis of
      these and other trace elements in real samples. Under optimal conditions, the
      limits of detection for Hg and Pb were 0.001 and 0.003 MUg L-1, respectively,
      with relative standard deviations (RSDs) better than 2.1% and 4.5% at a
      concentration of 1 MUg L-1. The accuracy of the HS-SPME-PD-OES system was
      validated by analysis of three Certified Reference Materials, including DORM-4
      (Hg, 412 +/- 36 MUg kg-1; Pb, 404 +/- 62 MUg kg-1), TORT-3 (Hg, 292 +/- 22 MUg kg
      1; Pb, 225 +/- 18 MUg kg-1) and SRM1568b (Hg, 5.53 +/- 0.58 MUg kg-1), providing
      analytical results in excellent agreement with certified values at the 95%
      confidence level. This method was also successfully used for the analysis of
      several real rice and water samples with satisfactory results (90-130% recoveries
      of added spikes).

PMID- 29457891
TI  - Pd-Catalyzed Asymmetric Dearomative Cycloaddition for Construction of Optically
      Active Pyrroloindoline and Cyclopentaindoline Derivatives: Access to 3a
      Aminopyrroloindolines.
AB  - Asymmetric dearomative [3 + 2] cycloaddition reactions of 3-nitroindoles with
      vinyl aziridine and vinyl cyclopropanes have been respectively successfully
      developed in the presence of a chiral box/Pd(0) complex. A series of
      enantiomerically enriched 3a-nitro-hexahydropyrrolo[2,3-b]indole and 8b
      nitrohexahydrocyclopenta[b]indole derivatives containing three contiguous chiral
      centers are smoothly obtained in high yields with satisfactory regio-, chemo-,
      and enantioselectivity. Remarkably, the synthetic utility of this process was
      demonstrated through direct reductive amination and functionalization of the
      carbon-carbon double bond of the desired products.

PMID- 29457892
TI  - Boronic-Acid-Catalyzed Regioselective and 1,2- cis-Stereoselective Glycosylation
      of Unprotected Sugar Acceptors via SNi-Type Mechanism.
AB  - Regio- and 1,2- cis-stereoselective chemical glycosylation of unprotected
      glycosyl acceptors has been in great demand for the efficient synthesis of
      natural glycosides. However, simultaneously regulating these selectivities has
      been a longstanding problem in synthetic organic chemistry. In nature, glycosyl
      transferases catalyze regioselective 1,2- cis-glycosylations via the SNi
      mechanism, yet no useful chemical glycosylations based on this mechanism have
      been developed. In this paper, we report a highly regio- and 1,2- cis
      stereoselective SNi-type glycosylation of 1,2-anhydro donors and unprotected
      sugar acceptors using p-nitrophenylboronic acid (10e) as a catalyst in the
      presence of water under mild conditions. Highly controlled regio- and 1,2- cis
      stereoselectivities were achieved via the combination of boron-mediated
      carbohydrate recognition and the SNi-type mechanism. Mechanistic studies using
      the KIEs and DFT calculations were consistent with a highly dissociative
      concerted SNi mechanism. This glycosylation method was applied successfully to
      the direct glycosylation of unprotected natural glycosides and the efficient
      synthesis of a complex oligosaccharide with minimal protecting groups.

PMID- 29457893
TI  - Kinetics, Thermodynamics, and Mechanism of a Novel Biphasic Solvent for CO2
      Capture from Flue Gas.
AB  - The main issue related to the deployment of the amine-based absorption process
      for CO2 capture from flue gas is its intensive energy penalty. Therefore, this
      study screened a novel biphasic solvent, comprising a primary amine e.g.,
      triethylenetetramine (TETA) and a tertiary amine e.g., N, N
      dimethylcyclohexylamine (DMCA), to reduce the energy consumption. The TETA-DMCA
      blend exhibited high cyclic capacity of CO2 absorption, favorable phase
      separation behavior, and low regeneration heat. Kinetic analysis showed that the
      gas- and liquid-side mass transfer resistances were comparable in the lean
      solution of TETA-DMCA at 40  degrees C, whereas the liquid-side mass transfer
      resistance became dominant in the rich solution. The rate of CO2 absorption into
      TETA-DMCA (4 M, 1:3) solution was comparable to 5 M benchmark monoethanolamine
      (MEA) solution. Based on a preliminary estimation, the regeneration heat with
      TETA-DMCA could be reduced by approximately 40% compared with that of MEA. 13C
      NMR analysis revealed that the CO2 absorption into TETA-DMCA was initiated by the
      reaction between CO2 and TETA via the zwitterion mechanism, and DMCA served as a
      CO2 sinker to regenerate TETA, resulting in the transfer of DMCA from the upper
      to lower phase. The proposed TETA-DMCA solvent may be a suitable candidate for
      CO2 capture.

PMID- 29457894
TI  - Small Molecule Allosteric Modulators of G-Protein-Coupled Receptors: Drug-Target
      Interactions.
AB  - G-protein-coupled receptors (GPCRs) are the largest class of signaling receptors
      that are most frequently targeted by therapeutic drugs. Allosteric modulators
      bound to GPCRs at allosteric sites provide the potential for differential
      selectivity and improved safety compared with traditional orthosteric ligands.
      The recent breakthroughs in GPCR structural biology have made structures of GPCRs
      from classes A, B, C, and F complexed with small-molecule allosteric modulators
      available. Knowledge of the detailed receptor-modulator interactions at the
      allosteric sites is useful for structure-based GPCR drug design of novel
      therapeutics. This Perspective comprehensively summarizes the current status of
      structural complexes between GPCRs and their small-molecule allosteric
      modulators, particularly the key receptor-modulator interactions at the
      allosteric sites. Then, the structural diversity of allosteric sites across four
      GPCR subfamilies is compared. This study is expected to contribute to the design
      of GPCR allosteric drugs with an improved therapeutic action.

PMID- 29457895
TI  - Periodic Trends in Actinyl Thio-Crown Ether Complexes.
AB  - In-cavity complexes and their bonding features between thio-crown (TC) ethers and
      f-elements are unexplored so far. In this paper, actinyl(VI) (An = U, Np, Pu, Am,
      and Cm) complexes of TC ethers have been characterized using relativistic density
      functional theory. The TC ether ligands include tetrathio-12-crown-4 (12TC4),
      pentathio-15-crown-5 (15TC5), and hexathio-18-crown-6 (18TC6). On the basis of
      the calculations, it is found that the "double-decker" sandwich structure of
      AnO2(12TC4)22+ and "side-on" structure AnO2(12TC4)2+ are changed to "insertion"
      structures for AnO2(15TC5)2+ and AnO2(18TC6)2+ due to increased size of the TC
      ether ligands. The actinyl monocyclic TC ether complexes are found to exhibit
      conventional conformations, with typical An-Oactinyl and An-Sligand distances and
      angles. Chemical bonding analyses by Weinhold's natural population analysis
      (NPA), natural localized molecular orbital (NLMO), and energy decomposed analysis
      (EDA), show that a typical ionic An-Sligand bond with the extent of covalent
      interaction between the An and S atoms primarily attributable to the degree of
      radial distribution of the S 3p atomic orbitals. The similarity and difference of
      the oxo-crown and TC ethers as ligands for actinide coordination chemistry are
      discussed. As soft S-donor ligands, TC ethers may be candidate ligands for
      actinide recognition and extraction.

PMID- 29457896
TI  - Nature of the Color of Borates with "Anti-Zeolite" Structure.
AB  - Crystals of the Mn xBa12(BO3)8-2 xF8 x phase were grown from a high-temperature
      solution. This new fluoride borate is built of positively charged [Ba12(BO3)6]6+
      blocks, the so-called "anti-zeolite" pattern. Using X-ray single-crystal
      diffraction, the bulk atomic arrangement in the centrosymmetric tetragonal unit
      cell in I4/ mcm could be elucidated. Crystals of the (MnF6)4- group-containing
      solid solution Mn xBa12(BO3)8-2 xF8 x are dark brown in color in contrast to the
      differently colored crystals of (LiF4)3- group-containing "anti-zeolite"
      LiBa12(BO3)7F4 ( P42 bc). According to the electron spin resonance and optical
      spectroscopic investigation, the absorption spectrum of LiBa12(BO3)7F4 crystals
      results from the absorption of light by both exciton and free charge carriers and
      can be tuned by varying the initial composition of the high-temperature solution.

PMID- 29457897
TI  - Macrocyclic Oligofurans: A Computational Study.
AB  - Macrocyclic oligothiophenes ( nCT) have been extensively explored for their
      unique optical and electronic properties, while their oxygen-containing
      analogues, macrocyclic oligofurans ( nCF), are not known. In this work,
      macrocyclic oligofurans bearing 5-16 units (5CF-16CF) are studied theoretically
      at the B3LYP/6-311G(d) level. We find that small macrocycles (6CF-8CF) exhibit
      planar or nearly planar geometries, low strain energies, low HOMO-LUMO gaps, and
      strong pi-conjugation as also reflected in their Raman spectra. These findings
      are in sharp contrast to macrocyclic oligothiophenes of the same size, which are
      distorted from planarity. Additionally, small macrocyclic furans display
      significantly lower reorganization energies and ionization potentials compared
      with their thiophene analogues. Overall, the observed properties highlight the
      potential of macrocyclic oligofurans to function as p-type organic electronic
      materials.

PMID- 29457898
TI  - Synthesis and Biological Evaluation of ( E)-4-Hydroxy-3-methylbut-2-enyl
      Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of
      Vgamma9/Vdelta2 T-Cell Immune Responses.
AB  - The aryloxy triester phosphoramidate prodrug approach has been used with success
      in drug discovery. Herein, we describe the first application of this prodrug
      technology to the monophosphate derivative of the phosphoantigen HMBPP and one of
      its analogues. Some of these prodrugs exhibited specific and potent activation of
      Vgamma9/Vdelta2 T-cells, which were then able to lyse bladder cancer cells in
      vitro. This work highlights the promise of this prodrug technology in the
      discovery of novel immunotherapeutics.

PMID- 29457899
TI  - Palladium-Catalyzed Selective Mono-/Tetraacetoxylation of o-Carboranes with
      Acetic Acid via Cross Dehydrogenative Coupling of Cage B-H/O-H Bonds.
AB  - A selective mono-/tetraacetoxylation of o-carboranes with acetic acid via cross
      dehydrogenative coupling of cage B-H/O-H bonds has been developed, and a series
      of mono- and tetraacetoxylated o-carboranes have been synthesized with moderate
      to good yields as well as good selectivity. Mechanistic studies indicate that the
      acetoxyl originates from acetic acid directly, and a nucleophilic addition of
      PdIV-oxo species and dehydration process is proposed.

PMID- 29457900
TI  - Three-Dimensional Structures Based on the Fusion of Chrysene and Spirobifluorene
      Chromophores for the Development of Blue OLEDs.
AB  - A new deep-blue chromophore containing a three-dimensionally (3D) shaped CS core
      composed of fused chrysene and spirofluorene units is synthesized. A pair of m
      terphenyl (TP) units is also substituted onto the CS core at two different sets
      of positions to form two additional compounds: CS-TPTP and TP-CS-TP. The TP-CS-TP
      compound showed the highest efficiency with an external quantum efficiency (EQE)
      of 3.05% and Commission Internationale de L'Eclairage coordinates (CIE) of
      (0.148, 0.098) corresponding to the emission of blue light. This approach for
      forming a new chromophore is expected to lead to the development of functional
      organic materials with excellent characteristics.

PMID- 29457901
TI  - C(sp3)-H Bond Functionalization of Benzo[c]oxepines via C-O bond Cleavage: Formal
      [3+3] Synthesis of Multisubstituted Chromans.
AB  - An efficient base-promoted C(sp3)-H bond functionalization strategy for the
      synthesis of multisubstituted chromans from the formal [3+3] cycloaddition of
      benzo[c]oxepines and electron-rich phenols has been developed. The corresponding
      4H-chromenes can be easily obtained in excellent yields by simple filtration from
      chromans. Preliminary mechanistic studies indicate that the C-O bond cleavage is
      the key step for the C(sp3)-H bond functionalization and that this reaction could
      have occurred through tandem C-O bond cleavage/Michael addition/annulation
      reactions.

PMID- 29457902
TI  - Multicolor Luminescence Switching and Controllable Thermally Activated Delayed
      Fluorescence Turn on/Turn off in Carbazole-Quinoxaline-Carbazole Triads.
AB  - We report a series of thermally activated delayed fluorescence (TADF) molecules
      with mechanochromic luminescence properties and reversible TADF turn on/off
      properties in solid state that are induced by the transition between amorphous
      and crystalline states. Additionally, multicolor altering through external
      stimulus is demonstrated. All of the studied compounds exhibited recovery of the
      initial states associated with narrower emission spectra. TADF organic light
      emitting diodes fabricated by solution processing rendered high external quantum
      efficiency up to 10.9% and luminance of 16 760 cd m-2.

PMID- 29457903
TI  - Excited-State Proton Transfer in 3-Cyano-7-azaindole: From Aqueous Solution to
      Ice.
AB  - We investigated the excited-state proton transfer (ESPT) reaction for 3-cyano-7
      azaindole (3CAI) in aqueous solution and in ice. 3CAI undergoes water-catalyzed
      ESPT in the aqueous solution, giving normal (355 nm) and proton transfer tautomer
      (~472 nm) emission bands. Detailed temperature-dependent studies showed that the
      values of activation free energy (Delta G?) were similar between N-H and N-D
      isotopes. Therefore, water-catalyzed ESPT involves a stepwise mechanism
      incorporating solvation equilibrium ( Keq) to form a 1:1 (molar ratio) water:3CAI
      cyclic hydrogen-bonded complex as an intermediate, followed by perhaps proton
      tunneling reaction. In sharp contrast, 3CAI in ice undergoes entirely different
      photophysical properties, in which 3CAI self-organizes to form a double-hydrogen
      bonded dimers at the grain boundary of the polycrystalline. Upon excitation, the
      dimer proceeds with a fast excited-state double proton transfer reaction, giving
      rise to solely a tautomer emission (~450 nm). The distinct difference in ESPT
      properties between water and ice makes azaindoles feasible for the investigation
      of water-ice interface property.

PMID- 29457904
TI  - Conflict in the Mechanism and Kinetics of the Barrierless Reaction between SH and
      NO2 Radicals.
AB  - There are some unsettled issues regarding the mechanism and kinetics of an
      important atmospheric reaction of NO2 radical with the SH radical. The existing
      mechanism is based on the formation of HSO and NO radicals, both of which can
      result only along one barrierless channel. However, the detection of NO radical
      has never been reported though the formation of HSO radical has been followed in
      some studies to determine the rate constants. The latter are mainly obtained by
      monitoring the SH decay, but rate constants are reported to be highly conflicting
      among the existing studies reporting its value ranging from 10-10 to 10-12 cm3
      molecule-1 sec-1. The present work attempts to resolve these issues by exploring
      various reaction pathways through the global reaction route mapping of the
      potential energy surface at the level of spin-unrestricted and spin-restricted
      coupled-cluster and density functional theories. The initial association of two
      radicals was found to proceed via two barrierless modes: (1) S-N association
      leading to HSNO2 and, (2) S-O association resulting in HSONO, in particular the
      cis-isomer. The kinetics of the barrierless pathways was investigated through
      rate constants computed using canonical variational transition state theory
      (CVTST) along with their temperature and pressure dependence investigated using
      the master equation. The rate constants calculated using spin-unrestricted
      methods are found to be in agreement with experimentally observed range of rate
      constant, and the formation of cis-HSONO (via mode 2) is observed to be the main
      contributing channel. Contrary to the results of spin-restricted calculations,
      the barrierless channel (mode 1) leading to the formation of HSNO2 is predicted
      to involve two bottlenecks when results using spin-unrestricted calculations were
      analyzed. Notably, the spin-unrestricted calculations predict a prereaction
      complex for the formation of S-N bond (via mode 1) which has been treated using
      Miller's unified transition state theory with a two transition state model. The
      fate of all the species involved in the reaction is critically evaluated in the
      present work, and the predictions made can be a subject of further experimental
      and theoretical studies involving radical-radical reactions.

PMID- 29457905
TI  - Computational Investigation of the Influence of Halogen Atoms on the
      Photophysical Properties of Tetraphenylporphyrin and Its Zinc(II) Complexes.
AB  - How the tetraphenylporphyrin (TPP) and its zinc(II) complexes (ZnTPP)
      photophysical properties (absorption energies, singlet-triplet energy gap and
      spin-orbit coupling contributions) can change due to the presence of an
      increasing number of heavy atoms in their molecular structures has been
      investigated by means of density functional theory and its time-dependent
      formulation. Results show that the increase of the atomic mass of the substituted
      halogen strongly enhances the spin-orbit coupling values, allowing a more
      efficient singlet-triplet intersystem crossing. Different deactivation channels
      have been considered and rationalized on the basis of El-Sayed and Kasha rules.
      Most of the studied compounds possess the appropriate properties to generate
      cytotoxic singlet molecular oxygen (1Deltag) and, consequently, they can be
      proposed as photosensitizers in photodynamic therapy.

PMID- 29457907
TI  - Deletion of Adipose Triglyceride Lipase Links Triacylglycerol Accumulation to a
      More-Aggressive Phenotype in A549 Lung Carcinoma Cells.
AB  - Adipose triglyceride lipase (ATGL) catalyzes the rate limiting step in
      triacylglycerol breakdown in adipocytes but is expressed in most tissues. The
      enzyme was shown to be lost in many human tumors, and its loss may play a role in
      early stages of cancer development. Here, we report that loss of ATGL supports a
      more-aggressive cancer phenotype in a model system in which ATGL was deleted in
      A549 lung cancer cells by CRISPR/Cas9. We observed that loss of ATGL led to
      triacylglycerol accumulation in lipid droplets and higher levels of cellular
      phospholipid and bioactive lipid species (lyso- and ether-phospholipids). Label
      free quantitative proteomics revealed elevated expression of the pro-oncogene SRC
      kinase in ATGL depleted cells, which was also found on mRNA level and confirmed
      on protein level by Western blot. Consistently, higher expression of
      phosphorylated (active) SRC (Y416 phospho-SRC) was observed in ATGL-KO cells.
      Cells depleted of ATGL migrated faster, which was dependent on SRC kinase
      activity. We propose that loss of ATGL may thus increase cancer aggressiveness by
      activation of pro-oncogenic signaling via SRC kinase and increased levels of
      bioactive lipids.

PMID- 29457906
TI  - Optimized Phenotypic Biomarker Discovery and Confounder Elimination via Covariate
      Adjusted Projection to Latent Structures from Metabolic Spectroscopy Data.
AB  - Metabolism is altered by genetics, diet, disease status, environment, and many
      other factors. Modeling either one of these is often done without considering the
      effects of the other covariates. Attributing differences in metabolic profile to
      one of these factors needs to be done while controlling for the metabolic
      influence of the rest. We describe here a data analysis framework and novel
      confounder-adjustment algorithm for multivariate analysis of metabolic profiling
      data. Using simulated data, we show that similar numbers of true associations and
      significantly less false positives are found compared to other commonly used
      methods. Covariate-adjusted projections to latent structures (CA-PLS) are
      exemplified here using a large-scale metabolic phenotyping study of two Chinese
      populations at different risks for cardiovascular disease. Using CA-PLS, we find
      that some previously reported differences are actually associated with external
      factors and discover a number of previously unreported biomarkers linked to
      different metabolic pathways. CA-PLS can be applied to any multivariate data
      where confounding may be an issue and the confounder-adjustment procedure is
      translatable to other multivariate regression techniques.

PMID- 29457908
TI  - Process Proteomics of Beer Reveals a Dynamic Proteome with Extensive
      Modifications.
AB  - Modern beer production is a complex industrial process. However, some of its
      biochemical details remain unclear. Using mass spectrometry proteomics, we have
      performed a global untargeted analysis of the proteins present across time during
      nanoscale beer production. Samples included sweet wort produced by a high
      temperature infusion mash, hopped wort, and bright beer. This analysis identified
      over 200 unique proteins from barley and yeast, emphasizing the complexity of the
      process and product. We then used data independent SWATH-MS to quantitatively
      compare the relative abundance of these proteins throughout the process. This
      identified large and significant changes in the proteome at each process step.
      These changes described enrichment of proteins by their biophysical properties,
      and identified the appearance of dominant yeast proteins during fermentation.
      Altered levels of malt modification also quantitatively changed the proteomes
      throughout the process. Detailed inspection of the proteomic data revealed that
      many proteins were modified by protease digestion, glycation, or oxidation during
      the processing steps. This work demonstrates the opportunities offered by modern
      mass spectrometry proteomics in understanding the ancient process of beer
      production.

PMID- 29457909
TI  - Droplet Translation Actuated by Photoelectrowetting.
AB  - In traditional electrowetting-on-dielectric (EWOD) devices, droplets are moved
      about a substrate using electric fields produced by an array of discrete
      electrodes. In this study, we show that a drop can be driven across a substrate
      with a localized light beam by exploiting the photoelectrowetting (PEW) effect, a
      light-activated variant of EWOD. Droplet transport actuated by PEW eliminates the
      need for electrode arrays and the complexities entailed in their fabrication and
      control, and offers a new approach for designing lab-on-a-chip applications. We
      report measurements of the maximum droplet speed as a function of frequency and
      magnitude of the applied bias, intensity of illumination, volume of the droplet,
      and viscosity and also introduce a model that reproduces these data.

PMID- 29457910
TI  - Mechanistic Analysis of Ion Association between Dendrigraft Poly-l-lysine and 8
      Anilino-1-naphthalenesulfonate at Liquid|Liquid Interfaces.
AB  - Molecular association between biocompatible dendritic polymers, dendrigraft poly
      l-lysines (DGLs), and an anionic fluorescent probe, 8-anilino-1
      naphthalenesulfonate (ANS-), was studied at the polarized water|1,2
      dichloroethane (DCE) interface. The fluorescence intensity of ANS measured in
      aqueous solution was enhanced by the coexistence of DGLs over a wide pH range (2
      < pH < 10), where ANS and DGL exist as a monoanionic form and a polycation,
      respectively. The voltammetric responses indicated that the positively charged
      DGLs were adsorbed at the water|DCE interface, whereas ANS- was transferred
      across the interface accompanied by the adsorption process. The interfacial
      behavior of the DGL-ANS associates was analyzed by potential-modulated
      fluorescence (PMF) spectroscopy. The PMF results demonstrated that the ion
      association between DGLs and ANS at the water|DCE interface is strongly affected
      by the applied potential and the dendritic generation of DGL. By applying
      appropriate potentials, the ANS anion was dissociated from its ion associate with
      DGLs at the interface and transferred into the organic phase, whereas DGLs
      remained in the aqueous phase. The Gibbs free energy of ion association (Delta
      GD...ANS) was estimated for the second-fourth generation DGLs (DGL-G2-G4) and the
      G4 polyamidoamine (PAMAM) dendrimer as a control. The highest stability of the
      DGL-G4-ANS associate manifested itself through Delta GD...ANS: DGL-G4-ANS (>G4
      PAMAM dendrimer-ANS) > DGL-G3-ANS > DGL-G2-ANS. The results elucidated the
      efficient anion-binding ability of higher generation DGLs and its potential
      dependence at the liquid|liquid interface.

PMID- 29457911
TI  - Preparation of Benzo[c]carbazol-6-amines via Manganese-Catalyzed Enaminylation of
      1-(Pyrimidin-2-yl)-1H-indoles with Ketenimines and Subsequent Oxidative
      Cyclization.
AB  - Manganese-catalyzed C2-H enaminylation of 1-(pyrimidin-2-yl)-1H-indoles with
      ketenimines is reported. The reaction provided 2-enaminylated indole derivatives
      in moderate to excellent yields with a broad substrate scope. A migration of the
      directing group pyrimidinyl occurred during this process. The synthesized 2
      enaminyl indoles could be conveniently converted into 5-aryl-7H-benzo[c]carbazol
      6-amines.

PMID- 29457912
TI  - Decreased resting gamma activity in adult attention deficit/hyperactivity
      disorder.
AB  - OBJECTIVES: To delineate task-free gamma activity in adult ADHD and healthy
      control subjects based on high-density EEG recordings. Relationship of gamma
      activity with symptom severity was also examined, since gamma activity is
      considered to be an index of network functions in the brain that underlie higher
      order cognitive processes. METHODS: Spontaneous EEG was recorded in adult ADHD
      subjects (N = 42; 25 methylphenidate-naive and 17 on methylphenidate treatment)
      and controls (N = 59) with eyes open. EEG absolute power gamma was investigated
      in the gamma1 (30.25-39 Hz) and gamma2 (39.25-48 Hz) frequency bands. RESULTS:
      Gamma1 and gamma2 activity was diminished in ADHD compared with healthy control
      subjects. The difference between ADHD and controls was the most pronounced in the
      right centroparietal region for both gamma1 and gamma2. Inverse associations were
      found between gamma1 and gamma2 activity and ADHD symptoms in centroparietal
      scalp regions. CONCLUSIONS: Gamma activity is reduced in adult ADHD, and the
      reduction has a predominantly right centroparietal distribution. Our findings are
      consistent with childhood ADHD literature with respect to diminished posterior
      gamma activity in patients, which may reflect altered dorsal attention network
      functions. Gamma abnormalities might provide a link between neurophysiological
      functioning and neuropsychological deficiencies, thereby offering an opportunity
      to investigate the neurobiological mechanisms that underlie the clinical symptoms
      of ADHD.

PMID- 29457913
TI  - Light emitting diode irradiation induced shape conversion of DNA-capped silver
      nanoparticles and their antioxidant and antibacterial activities.
AB  - Due to size- and shape-dependent properties, a shape-controlled synthesis of
      silver nanoparticles (AgNPs) is one of the research challenging topics for their
      production and potential applications. This work reported the simple eco-friendly
      syntheses of different shaped AgNPs controlled by the plasmid DNA content and
      light emitting diodes (LEDs) irradiation. The synthesized AgNPs appeared as
      yellow, orange and green colloidal AgNPs, which transmission electron microscope
      (TEM) images revealed their different shapes; spherical AgNPs, a mixture of
      spherical and hexagonal AgNPs, and a mixture of spherical, hexagonal and corner
      truncated triangle AgNPs, respectively. The average sizes of spherical, hexagonal
      and corner-truncated triangle AgNPs in the green colloidal solution were 12.32 +/
      2.22, 23.03 +/- 6.62 and 15.84 +/- 4.31 nm, respectively. The analyses of X-ray
      diffraction, selected area electron diffraction and high-resolution TEM indicated
      the crystalline nature of the synthesized particles as the face-centred cubic
      silver. All synthesized AgNPs exhibited antioxidant activities similarly, whereas
      the yellow colloidal AgNPs exhibited the strongest antibacterial activity against
      both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus as
      compared with the green and orange colloidal AgNPs.

PMID- 29457914
TI  - Estimating road traffic injuries in Jinja district, Uganda, using the capture
      recapture method.
AB  - Road traffic injuries (RTIs) are commonly under-reported in low-and-medium-income
      countries. This study aimed to estimate the number of RTIs and determine the
      magnitude of under-reporting by traffic police and hospital registries. A two
      source capture-recapture method was applied to RTI data from police and hospital
      registries. Seven matching variables; sex of the injured, date, place, time, day
      of crash and road user type were used to get the matched cases. Police
      independently reported 46 RTIs and the hospitals reported 206 RTIs. Using the
      capture-recapture analysis, both sources estimated 313 RTIs (95% CI 273-343). The
      police registry captured 14.4% of the estimated number of RTIs and the hospitals
      captured 60.4%. The estimated number of RTIs was higher than reported by either
      the police or the hospitals alone. Neither the police nor the hospitals provided
      accurate data on RTIs, calling for the strengthening of both sources of data.

PMID- 29457915
TI  - How good are we at selecting students that meet our mission? Outcomes of the 2011
      and 2012 entering classes selected by a locally developed multiple mini
      interview.
AB  - BACKGROUND: Can a locally developed multiple mini interview (MMI) process lead to
      outcomes reflective of local values and mission? METHODS: In 2017, the authors
      performed a retrospective analysis of the relationship of MMI with multiple
      choice-based outcomes and non-multiple-choice-based outcomes, including clerkship
      competencies, OSCE, scholarship/service/leadership, academic honor society
      induction, peer and faculty humanism nominations, and overall performance at
      graduation for two entering classes with acceptance decisions based exclusively
      on a locally developed MMI. RESULTS: There was no association between MMI and
      performance on multiple-choice-based examinations. For other outcomes, the effect
      size of MMI for OSCE was small and leadership/service and scholarship did not
      correlate with MMI score. For clerkship competencies, there was medium effect
      size for patient care, practice-based learning and improvement, interpersonal and
      communication skills, and cultural competence. Highest and lowest quartile MMI
      scorers were no different in academic honor society induction; however, top
      quartile MMI scorers received more humanism votes versus last quartile and were
      more likely rated outstanding or excellent graduates. CONCLUSIONS: Local
      development of MMI and of admissions processes with sole reliance on MMI for
      final acceptance decisions will not affect academic preparation/medical school
      performance in multiple-choice-based assessments but can lead to locally desired
      attributes in students.

PMID- 29457916
TI  - Systematic review of psychiatric signs in Niemann-Pick disease type C.
AB  - OBJECTIVES: We conducted the first systematic literature review and analysis of
      psychiatric manifestations in Niemann-Pick disease type C (NPC) to describe: (1)
      time of occurrence of psychiatric manifestations relative to other disease
      manifestations; and (2) frequent combinations of psychiatric, neurological and
      visceral disease manifestations. METHODS: A systematic EMBase literature search
      was conducted to identify, collate and analyze published data from patients with
      NPC associated with psychiatric symptoms, published between January 1967 and
      November 2015. RESULTS: Of 152 identified publications 40 were included after
      screening that contained useable data from 58 NPC patients (mean [SD] age at
      diagnosis of NPC 27.8 [15.1] years). Among patients with available data,
      cognitive, memory and instrumental impairments were most frequent (90% of
      patients), followed by psychosis (62%), altered behavior (52%) and mood disorders
      (38%). Psychiatric manifestations were reported before or at neurological disease
      onset in 41 (76%) patients; organic signs (e.g., hepatosplenomegaly, hearing
      problems) were reported before psychiatric manifestations in 12 (22%).
      Substantial delays to diagnosis were observed (5-6 years between psychiatric
      presentation and NPC diagnosis). CONCLUSIONS: NPC should be considered as a
      possible cause of psychiatric manifestations in patients with an atypical disease
      course, acute-onset psychosis, treatment failure, and/or certain combinations of
      psychiatric/neurological/visceral symptoms.

PMID- 29457917
TI  - Clinical characteristics and long-term prognosis of elderly-onset Crohn's
      disease.
AB  - OBJECTIVES: This study aimed to evaluate the clinical characteristics and
      clinical course of Asian elderly-onset Crohn's disease (EOCD) patients in a large
      well-defined cohort of South Korean IBD patients. MATERIALS AND METHODS: From the
      Asan inflammatory bowel disease registry, we identified 29 EOCD patients
      (diagnosed with CD in age of 60 years or over) out of 2989 CD patients (1.0%).
      After excluding two patients with unclear data, 27 EOCD were matched with 108
      young-onset CD (YOCD) and 108 middle age-onset CD (MOCD) for the interval from
      symptom onset to diagnosis (+/-3 years) and follow-up duration (+/-3 years).
      RESULTS: Females were predominant in the EOCD group (59.3%) compared to MOCD
      (31.5%) and YOCD (29.6%) groups (p = .012). In EOCD group, terminal ileal
      location was the most common (63.0%) at diagnosis, whereas ileocolonic location
      in other groups (57.4% in MOCD and 78.7% in YOCD, respectively) (p < .001).
      Patients with perianal fistula at CD diagnosis were less common (14.8% in EOCD
      vs. 28.7% in MOCD vs. 49.1% in YOCD, p < .001). During follow-up, thiopurines
      were used less frequently in the EOCD group (48.1% in EOCD vs. 87.0% in MOCD vs.
      89.8% in YOCD, p < .001), but the risk for intestinal resection was comparable
      among three groups (p = .583). CONCLUSIONS: EOCD may have a better clinical
      course than MOCD and YOCD, as demonstrated by the similar risk for intestinal
      resection despite the less frequent use of thiopurines.

PMID- 29457918
TI  - Quality of life among patients during subacute phase following stroke during
      hospitalisation period in Shanghai.
AB  - OBJECTIVE: This study aimed to investigate the factors influencing the quality of
      life of in-hospital subacute stroke patients. METHODS: The patients of subacute
      stroke (within four weeks) in our institution between 2015 and 2016 were
      recruited. Patients' characteristics and QOL were obtained from medical charts
      and stroke-specific quality of life scale (SS-QOL). Associations of each domain
      in SS-QOL with socio-demographic, clinical factors and patient satisfaction were
      investigated using the linear regression models. RESULTS: Among the 203 subjects,
      60 were diagnosed as large artery atherosclerosis (LAA), 80 were small-artery
      occlusion (SAO), 28 were cardioembolism (CE) and 35 were intracranial haemorrhage
      (ICH). The ICH group had the worst self-care ability and upper extremity
      function. Worse severity of stroke was associated with lower levels of language
      ability, mobility, mood status and upper-extremity function. Participants who had
      better satisfaction had high levels of capability of conducting family roles,
      positive emotions, personality consistency, self-care ability and capacity of
      conducting social roles. CONCLUSIONS: The level of patient satisfaction, duration
      of hospitalisation and the severity of stroke were found to be the three
      important factors associated with SS-QOL at hospital discharge, indicating
      doctors might assist patients adjust to the consequences of stroke and improve
      the QOL of subacute stroke.

PMID- 29457919
TI  - Enterobacteriaceae Antibiotic Resistance in Ready-to-Eat Foods Collected from
      Hospital and Community Canteens: Analysis of Prevalence.
AB  - Foodborne diseases and antibiotic resistance are serious widespread health
      problems in the contemporary world. In this study, we compared the
      microbiological quality of ready-to-eat (RTE) foods found in community canteens
      versus hospital canteens in Rome, Italy, focusing on detection and quantification
      of Enterobacteriaceae and the antibiotic resistance of these bacteria. Our
      findings show a remarkable difference in Enterobacteriaceae contamination between
      RTE foods distributed in community canteens (33.5% of samples) and those
      distributed in hospital canteens (5.3% of samples). This result highlights
      greater attention to good manufacturing practices and good hygiene practices by
      the food operators in hospitals compared with food operators in community
      canteens. As expected, a higher percentage of cold food samples (70.9%) than of
      hot food samples (10.8%) were positive for these bacteria. Excluding the
      intrinsic resistance of each bacterial strain, 92.3% of the isolated strains were
      resistant to at least one antibiotic, and about half of the isolated strains were
      classified as multidrug resistant. The prevalence of multidrug-resistant strains
      was 50% in the community samples and 33.3% in hospital canteens. Our results
      indicate that approximately 38% of RTE foods provided in community canteens is
      not compliant with microbiological food safety criteria and could be a special
      risk for consumers through spread of antibiotic-resistant strains. Hygienic
      processing and handling of foods is necessary for both hospital and community
      canteens.

PMID- 29457920
TI  - A critical appraisal of the reporting quality of published randomized controlled
      trials in the fall injuries.
AB  - To evaluate the quality of reporting in published randomized controlled trials
      (RTCs) in the field of fall injuries. The 188 RTCs published between 2001 and
      2011, indexed in EMBASE and Medline databases were extracted through searching by
      appropriate keywords and EMTree classification terms. The evaluation
      trustworthiness was assured through parallel evaluations of two experts in
      epidemiology and biostatistics. About 40%-75% of papers had problems in reporting
      random allocation method, allocation concealment, random allocation
      implementation, blinding and similarity among groups, intention to treat and
      balancing benefits and harms. Moreover, at least 10% of papers
      inappropriately/not reported the design, protocol violations, sample size
      justification, subgroup/adjusted analyses, presenting flow diagram, drop outs,
      recruitment time, baseline data, suitable effect size on outcome, ancillary
      analyses, limitations and generalizability. Considering the shortcomings found
      and due to the importance of the RCTs for fall injury prevention programmes,
      their reporting quality should be improved.

PMID- 29457921
TI  - Ribociclib for the treatment of hormone receptor-positive, human epidermal growth
      factor receptor 2-negative advanced breast cancer.
AB  - INTRODUCTION: The emergence of cyclin-dependent kinases 4 and 6 (CDK4/6)
      inhibitors marked a significant advancement in the treatment of advanced breast
      cancer. Ribociclib is an orally bioavailable, highly selective inhibitor of
      CDK4/6. In combination with various endocrine therapies, ribociclib has
      demonstrated clinical activity as a first-line therapy for patients with HR+,
      HER2- advanced breast cancer, without compromising the favorable toxicity profile
      associated with endocrine therapy. Thus, ribociclib is now considered a new
      standard of care for HR+, HER2- advanced breast cancer. Areas covered: This
      review provides a concise overview of the preclinical and clinical development of
      ribociclib, including evidence of its clinical activity and safety profile when
      combined with endocrine therapy in HR+, HER2- advanced breast cancer. Expert
      commentary: CDK4/6 inhibition represents a promising treatment option for
      patients with HR+ metastatic breast cancer. Ribociclib significantly improved
      progression-free survival in patients receiving first-line endocrine therapy for
      HR+, HER2- advanced breast cancer. Planned and ongoing trials investigating
      ribociclib in combination with other endocrine therapies and in various clinical
      settings will help to determine the optimal treatment sequence for different
      patient populations.

PMID- 29457922
TI  - Evaluation of risk factors for recurrent primary common bile duct stone in
      patients with cholecystectomy.
AB  - OBJECTIVES: Recurrence of primary common bile duct (CBD) stone commonly occurs
      after complete removal of CBD stones in patients with cholecystectomy. This study
      aimed to investigate potential risk factors for the recurrence of primary CBD
      stones after endoscopic treatment. MATERIALS AND METHODS: Between January 2005
      and December 2015, the endoscopic retrograde cholangiopancreatography (ERCP)
      database of our medical center was retrospectively reviewed; information
      regarding eligible patients who had recurrent CBD stones with a history of
      previous cholecystectomy was collected. The characteristics of the patients, CBD
      stone, CBD and ERCP-related factors were analyzed. RESULTS: The recurrence rate
      of CBD stone was 18.5% (115/622) after endoscopic treatment in patients with
      cholecystectomy. In univariate analysis, the number of CBD stones (>=2), CBD
      stone diameter (>=10 mm), stone composition, stone consistency, CBD diameter
      (>=15 mm), bile duct dilatation pattern, sharp bile duct angulation (<145 degrees
      ), balloon dilatation, large balloon (>12 mm) dilatation, endoscopic mechanical
      lithotripsy, endoscopic sphincterotomy, and endoscopic papillary balloon
      dilatation alone method were significant between the non-recurrence and
      recurrence groups. However, in multivariate analysis (based on the binary
      logistic regression method), the number of CBD stones (>=2) (adjusted odds ratio
      [AOR] 3.232; 95% confidence interval [CI] 1.344-7.773; p = .009), cholesterol
      stone (AOR 2.824; 95% CI 1.175-6.786; p =.02) and sharp bile duct angulation
      (<145 degrees ) (AOR 2.462; 95% CI 1.062-5.711; p = .036) were independent risk
      factors of CBD stone recurrence after cholecystectomy. CONCLUSIONS: CBD stone
      number (>=2), cholesterol stone and sharp bile duct angulation (<145 degrees )
      are associated with recurrent common bile duct stones after cholecystectomy.

PMID- 29457923
TI  - Flipping social determinants on its head: Medical student perspectives on the
      flipped classroom and simulated patients to teach social determinants of health.
AB  - BACKGROUND: Inequalities in healthcare are increasing. Engaging medical students
      to tackle this urgent challenge alongside clinical sciences can be demanding.
      This study examines medical student perceptions of a flipped approach to health
      inequalities co-designed by faculty and sixth-year students. INNOVATION: A
      flipped learning session was piloted for year 4 medical students combining an
      online lesson followed by a tutorial with a simulated patient. METHODS: A mixed
      methods approach collected questionnaire data using 4-point Likert scales and
      free text answers. A semi-structured group interview was conducted with six
      voluntary participants. RESULTS: Two hundred and eighty-nine students completed
      questionnaires. 85% (n = 246) completed the online lesson. Students agreed the
      session helped their understanding of key concepts (mean 3.2), was improved by
      having an actor (mean = 3.6), and was enjoyable (mean = 3.2). Thematic analysis
      of qualitative questionnaire and interview data revealed three themes:
      engagement; structure; and attitudes towards social determinants of health. The
      simulation increased clinical relevance and students gained understanding of the
      impact of health inequalities upon individuals. CONCLUSIONS: This paper indicates
      flipped learning can increase clinical relevance and engagement in population
      health and person-centered care. Further work could assess changes in practice
      and attitudes of future doctors in tackling such global health challenges.

PMID- 29457924
TI  - Factors influencing audiologists' perception of moral climate in the workplace.
AB  - OBJECTIVE: The purpose of this study was to assess audiologists' perceptions of
      ethics and moral climate in the workplace. DESIGN: The Ethics Environmental
      Questionnaire (EEQ) was sent out to all audiologists registered with the
      professional body Audiology Australia. Participants were also invited to
      undertake a semi-structured interview. STUDY SAMPLE: A total of 301 audiologists
      completed the questionnaire. Eight of these participants also agreed to complete
      the interview. RESULTS: The overall mean on the EEQ was approximately equivalent
      to that of a positive ethical environment, with the exception of those working in
      adult rehabilitation settings who scored significantly poorer. Scores were
      significantly associated with state and age. Qualitative analysis from the
      interviews found that sales pressure from employers was the dominant cause for
      concern amongst the group. CONCLUSIONS: For those working in adult
      rehabilitation, moral distress is most likely to occur as the result of
      conflicting goals between the organisation and the audiologist. There is a need
      to regulate the practice at an organisational as well as individual level to
      ensure the focus remains on ethical practice.

PMID- 29457925
TI  - Controlled release of mitomycin C from PHEMAH-Cu(II) cryogel membranes.
AB  - Molecular imprinting technique was used for the preparation of antibiotic and
      anti-neoplastic chemotherapy drug (mitomycin C) imprinted cryogel membranes (MMC
      ICM). The membranes were synthezied by using metal ion coordination interactions
      with N-methacryloyl-(l)-histidine methyl ester (MAH) functional monomer and
      template molecules (i.e. MMC). The 2-hydroxyethyl methacrylate (HEMA) monomer and
      methylene bisacrylamide (MBAAm) crosslinker were used for the preparation of
      mitomycin C imprinted cryogel membranes by radical suspension polymerization
      technique. The imprinted cryogel membranes were characterized by scanning
      electron microscopy (SEM), Brunauer-Emmett-Teller (BET), Fourier transform
      infrared spectroscopy-attenuated total reflectance (FTIR-ATR) and swelling degree
      measurements. Cytotoxicity of MMC-ICMs was investigated using mouse fibroblast
      cell line L929. Time-dependent release of MMC was demonstrated within 150 h from
      cryogel membranes. Cryogels demonstrated very high MMC loading efficiency (70
      80%) and sustained MMC release over hours.

PMID- 29457926
TI  - The contribution of theory to the design, delivery, and evaluation of
      interprofessional curricula: BEME Guide No. 49.
AB  - BACKGROUND: Interprofessional curricula have often lacked explicit reference to
      theory despite calls for a more theoretically informed field that illuminates
      curricular assumptions and justifies curricular practices. AIM: To review the
      contributions of theory to the design, delivery, and evaluation of
      interprofessional curricula. METHODS: Four databases were searched (1988-2015).
      Studies demonstrating explicit and a high-quality contribution of theory to the
      design, delivery or evaluation of interprofessional curricula were included. Data
      were extracted against a comprehensive framework of curricular activities and a
      narrative synthesis undertaken. RESULTS: Ninety-one studies met the inclusion
      criteria. The majority of studies (86%) originated from the UK, USA, and Canada.
      Theories most commonly underpinned "learning activities" (47%) and "evaluation"
      (54%). Theories of reflective learning, identity formation, and contact
      hypothesis dominated the field though there are many examples of innovative
      theoretical contributions. CONCLUSIONS: Theories contribute considerably to the
      interprofessional field, though many curricular elements remain under-theorized.
      The literature offers no "gold standard" theory for interprofessional curricula;
      rather theoretical selection is contingent upon the curricular component to which
      theory is to be applied. Theories contributed to interprofessional curricula by
      explaining, predicting, organizing or illuminating social processes embedded in
      interprofessional curricular assumptions. This review provides guidance how
      theory might be robustly and appropriately deployed in the design, delivery, and
      evaluation of interprofessional curricula.

PMID- 29457927
TI  - Structural fingerprints, interactions, and signaling networks of RAS family
      proteins beyond RAS isoforms.

PMID- 29457928
TI  - An atraumatic retractor for interdisciplinary use in conventional laparoscopy and
      robotic surgery.
AB  - BACKGROUND: The removal of obstacles from the surgical field is a crucial aspect
      of any procedure in gynecological, urological or visceral laparoscopic surgery.
      Reliable instruments and skilled assistance are essential for the smooth
      execution of procedures. Blunt forceps are commonly used to keep tissue away from
      the operating field. The range of existing instruments has been enhanced by the
      introduction of laparoscopic retractors. However, no laparoscopic retractor can
      be used without causing tissue damage. MATERIAL AND METHODS: We describe the
      ALKATOUT retractor, an innovative laparoscopic retractor designed for atraumatic
      assistance in any laparoscopic procedure including robotic surgery. The
      advantages of this laparoscopic instrument were evaluated in a single-center
      study. RESULTS: The retractor has been used successfully in a variety of
      gynecological procedures and tested in laparoscopic procedures on human body
      donors. CONCLUSIONS: The results of a single-center questionnaire completed by 25
      operating room staff (surgical nurses, residents, and specialists) confirm the
      advantages of the ALKATOUT retractor.

PMID- 29457929
TI  - Growth of the James Cook University Medical Program: Maintaining quality,
      continuing the vision, developing postgraduate pathways.
AB  - BACKGROUND: James Cook University (JCU) enrolled its first cohort of 64 in 2000
      into a 6-year undergraduate medical program aimed at producing graduates capable
      of meeting the needs of North Queensland, Australia, with a focus on rural,
      remote, Indigenous and tropical health. The school's 1465 graduates over 13
      cohorts who have a pattern of practice likely to meet the region's health needs.
      The JCU course was the first new Australian medical program for 25 years. The
      number of Australian medical schools has since doubled, while enrollments have
      almost tripled. METHODS: JCU's course features innovations such as dispersed,
      community-based education, rurally-focused selection, extended rural placements,
      and an emphasis on community needs - which are all now mainstream. This paper
      traces developments at JCU over the past decade, illustrating parallels with the
      broader Australian scene. RESULTS: Maintaining quality and educational integrity
      while numbers grow is challenging. The course has undergone modest curriculum
      redesign, but the fundamental elements are intact. The focus on meeting the
      region's needs remains, with some evolution of its mission to include social
      accountability and the needs of underserved populations. CONCLUSIONS:
      Postgraduate pathways are an important priority. Regional training hubs are being
      developed to support local pipelines into specialty practice. Queensland's Rural
      Generalist Pathway provides an incentivised pathway to rural practice while
      Generalist Medical Training provides a local training pipeline into general
      practice and rural medicine. As these initiatives mature, communities should
      benefit as JCU and other Australian programs continue to address local workforce
      needs.

PMID- 29457930
TI  - Nano-loaded human umbilical cord mesenchymal stem cells as targeted carriers of
      doxorubicin for breast cancer therapy.
AB  - The main challenge of anticancer drugs is poor tumor targeting. Now cellular
      carriers are widely investigated to deliver anticancer agents. As an ideal
      cellular candidate, human umbilical cord derived mesenchymal stem cells (hUC
      MSCs) possess inherent tropism potential to tumor. Here, we constructed hUC-MSCs
      carrying transferrin-inspired-nanoparticles that contain doxorubicin(hUC-MSCs-Tf
      inspired-NPs) to achieve enhanced anti-tumor efficacy and made an evaluation.
      Results represented that hUC-MSCs-Tf-inspired-NPs not only exhibit the controlled
      release property of Tf-inspired-NPs, but also integrate tumor tropism and
      penetrative abilities of MSCs. The tumor volume of nude mice bearing breast
      cancer MCF-7 treated with hUC-MSCs-Tf-inspired-NPs, was remarkably reduced
      compared to those treated with free drug or Tf-inspired-NPs. Thus, Tf-inspired
      NPs loaded hUC-MSCs have a potential to deliver anticancer drugs.

PMID- 29457931
TI  - Synthesis and Characterization of Nanodiamond-Growth Factor Complexes Toward
      Applications in Oral Implantation and Regenerative Medicine.

PMID- 29457932
TI  - Oral Health-Related Outcomes in Edentulous Patients Treated With Mandibular
      Implant-Retained Dentures Versus Complete Dentures: Systematic Review With Meta
      Analyses.
AB  - The objective of this systematic review was to determine the effect on oral
      health-related outcomes from mandibular implant-retained dentures opposing
      maxillary complete dentures in edentulous middle-age and older adults, compared
      with complete removable dentures in both arches. Randomized controlled trials
      included participants with an average age of 65 years or older. The Cochrane
      Library, MEDLINE, and Web of Science were searched. A total of 228 abstracts were
      reviewed for inclusion criteria, with 14 trials included and analyzed for risk of
      bias. Eleven of these studies were assessed as being at an unclear risk of bias,
      and 3 were at high risk. Mandibular implant-retained overdenture therapy showed
      statistically significant improvements in the patients' general satisfaction ( P
      = .003), oral health-related quality of life ( P < .001), and chewing ability ( P
      < .001), over the patients with complete dentures. There were no significant
      differences in the percentage of patients who were satisfied with their
      overdentures vs complete dentures for comfort, retention, esthetics, or chewing
      ability; however, only 2 studies reported these outcomes. In terms of nutritional
      status 1 year after treatment, vitamin B12 blood levels increased significantly
      in the implant-retained group ( P = .003), but not the other nutritional values.
      Implant-retained mandibular overdentures are an option for middle-aged and
      elderly edentulous patients as they significantly improve some of the outcomes;
      however, the quality of the evidence was moderate/low, due to the small number of
      studies included and the risk of bias. Future research should include objective
      outcomes such as masticatory performance, chewing efficacy, and muscular
      coordination.

PMID- 29457933
TI  - Computer-Guided Inferior Alveolar Nerve Lateralization With Simultaneous Implant
      Placement: A Preliminary Report.
AB  - Placement of dental implants in the posterior mandibular alveolar ridges may
      become a challenging procedure because of limited bone height between the crest
      of the ridge and the inferior alveolar canal. The aim of this study was to
      introduce an innovative, less invasive, highly accurate, and easy surgical
      technique of inferior alveolar nerve lateralization in the posterior deficient
      mandible using a special customized 3-dimensional-printed surgical guide to
      enhance the bone height for implant placement. This case series study included 7
      patients with unilateral edentulous mandibular alveolar ridges. Customized
      surgical guides were manufactured using fused deposition modeling technology to
      accurately place a rectangular window to uncover the canal and also for immediate
      placement of dental implants in all cases. The results of this limited study
      provided information on an innovative technique that decreased intraoperative
      time and demonstrated decreased risks for (1) inferior alveolar nerve injury and
      (2) postoperative nerve dysfunction.

PMID- 29457935
TI  - Customized Titanium Lattice Structure in Three-Dimensional Alveolar Defect: An
      Initial Case Letter.

PMID- 29457934
TI  - Early Placement of Dental Implants in Maxillary Sinus Grafted With Leukocyte and
      Platelet-Rich Fibrin and Deproteinized Bovine Bone Mineral.
AB  - This case report aimed to describe the effects of leukocyte and platelet-rich
      fibrin (L-PRF) associated with demineralized bovine bone mineral (DBBM) and
      absorbable collagen membrane (CM) on bone regeneration in maxillary sinus
      augmentation. A 59-year-old male patient was referred to the Department of
      Periodontology for implant rehabilitation of his edentulous upper jaw. The
      treatment plan involved maxillary sinus augmentation followed by implant
      installations. A split-mouth design was employed in which the right maxillary
      sinus was filled using L-PRF, DBBM, and CM; the left side was filled with DBBM
      and CM. After 4 and 8 months postoperatively, 2 dental implants were installed in
      each of the right and left maxillary sinuses. Cone-beam computerized tomography
      (CBCT) was taken before and after sinus augmentation for evaluation of
      tridimensional bone volume alterations. Bone biopsies were harvested from the
      implant sites for histomorphometric evaluation. Resonance frequency analysis was
      employed immediately after implant placement and before prosthetic rehabilitation
      for evaluation of implant stability. Implants were loaded 10 months after sinus
      augmentation. CBCT analysis showed a higher resorption rate in the right side of
      the maxillary sinus (L-PRF + DBBM) compared to the left side (22.25% and 8.95%,
      respectively). Implant stability quotients were above 68 in all time-points for
      both groups. Histomorphometric analysis showed a high amount of newly formed bone
      when L-PRF was used compared with DBBM alone (2 118 102 and 975 535 mm3,
      respectively). Taken together, both techniques were effective for maxillary sinus
      augmentation, however the addition of L-PRF to the graft allowed early implant
      placement and accelerated bone healing in the conditions studied.

PMID- 29457936
TI  - Prevalence, Structure, and Distribution of Novel Parasite Cysts Containing
      Dracunculus Species in River Otters ( Lontra canadensis) from Arkansas.
AB  - Adult female guinea worms ( Dracunculus spp.) usually are reported to occur
      singly in the extremities of their hosts, from which they deliver their larvae
      into the water through fistulae in the host's skin. We visually examined for the
      presence of worms in the fascia of the limbs of skinned carcasses of 184 river
      otters ( Lontra canadensis) harvested in Arkansas and report observations of
      cysts on wrists and ankles found on 12 otters. Cysts averaged 15.6 * 24.6 mm in
      diameter, were round to oval, and contained masses of up to 19 adult female
      Dracunculus sp. (mean 6.7). We speculate that high levels of infection in
      consumed paratenic hosts might have caused high infection rates, leading to large
      cyst formation in otters, as larvigerous Dracunculus sp. females accumulated in
      extremities. No males were discovered during the study, so identification of a
      sample of worms was based on molecular techniques.

PMID- 29457937
TI  - Support with nutrition for women receiving chemotherapy for breast cancer.
AB  - Nurses are in a unique position to provide nutritional advice and information to
      women with breast cancer who are undergoing chemotherapy, supporting them with
      making decisions regarding nutrition and diet. This narrative review evaluated
      the research evidence relating to the nutritional challenges experienced during
      chemotherapy and the most effective approaches for supporting women in dietary
      choice. Weight gain was identified as a specific problem for women undergoing
      chemotherapy. The evidence indicated that information about nutrition and food
      preparation support may go some way in assisting women to overcome some of the
      nutrition-related difficulties experienced during chemotherapy treatment for
      breast cancer. However, further research is required to better inform person
      centred nursing practice in this area.

PMID- 29457938
TI  - Predicting and preventing alcohol relapse in alcohol-related liver disease.
AB  - BACKGROUND: despite a 450% increase in UK alcohol-related liver disease mortality
      over the past 30 years, little evidence-based guidance exists regarding
      preventing recidivism post-liver transplant for alcohol-related liver disease.
      METHOD: a systematic literature review was conducted to identify demographic
      variables predictive of alcohol relapse and effective psychosocial interventions
      for alcohol-related liver disease patients post-liver transplant. RESULTS:
      variables most significantly predictive of alcohol relapse post-transplant were
      less than 12 months pre-liver transplant abstinence; patients with children; poor
      pre-liver transplant psychosomatic evaluation; non-compliance with post-liver
      transplant treatment plan; and patients with active insurance policies.
      Structured management was the most effective psychosocial intervention in
      preventing alcohol relapse. CONCLUSION: findings should be interpreted
      cautiously, due to limited and poor-quality evidence. Rigorously designed further
      research of the psychosocial interventions targeting predictive demographic
      variables is recommended.

PMID- 29457940
TI  - Needed: a retention strategy.

PMID- 29457939
TI  - Holistic patient-centred care.

PMID- 29457941
TI  - The impact of nurse managers' leadership styles on ward staff.
AB  - AIM: to explore the nature of leadership styles used by the nursing management
      team, as perceived by nurses working at the bedside. BACKGROUND: leadership style
      is related to job satisfaction, staff retention, costs, and quality of care. The
      leadership styles of managers can be crucial in the healthcare setting, but very
      few studies have focused on them. METHOD: the study employed qualitative
      methodology, involving 35 nurses working in different specialties of a medical
      city in Saudi Arabia. Data collection consisted of completing demographic and
      professional information and a semi-structured interview using open-ended
      questions. ANALYSIS: a phenomenologic-hermeneutic approach was used to identify
      major themes. RESULTS: the findings showed that participants described four types
      of leadership styles: relational leadership, preferential leadership,
      communication chain leadership, and ineffectual leadership. CONCLUSION: the
      leadership style employed by nurse managers has a major impact on nurses'
      satisfaction, turnover, and the quality of patient care they deliver.

PMID- 29457942
TI  - Management of chronic oedema in patients with multiple morbidity.
AB  - Marie Todd, Lymphoedema Clinical Nurse Specialist, Specialist Lymphoedema
      Service, Glasgow, discusses the difficulties of caring for people with
      compounding conditions.

PMID- 29457943
TI  - Strategies to future-proof and enhance the nursing workforce.
AB  - Emeritus Professor Alan Glasper, University of Southampton, discusses a new
      initiative by Health Education England to address staffing challenges facing the
      health service.

PMID- 29457944
TI  - My light bulb moment.

PMID- 29457945
TI  - Factors that influence nurses' assessment of patient acuity and response to acute
      deterioration.
AB  - BACKGROUND: nurses play a crucial role in the early recognition and management of
      the deteriorating patient. They are responsible for the care they provide to
      their patients, part of which is the monitoring of vital signs (blood pressure,
      pulse, respiratory rate and temperature), which are fundamental in the
      surveillance of deterioration. The aim of this study was to discover what factors
      influence how nurses assess patient acuity and their response to acute
      deterioration. METHODS: a generic qualitative approach was used. Some 10 nurses
      working in an acute NHS trust were interviewed using a semi- structured approach,
      with equal representation from medical and surgical inpatient wards. RESULTS: the
      main themes identified were collegial relationships, intuition, and
      interpretation of the MEWS system (Modified Early Warning Score). Collegial
      relationships with the medical staff had some influence on the nurses'
      assessment, as they tended to accept the medical peers' assessment as absolute,
      rather than their own assessment. It was also highlighted that nurses relied on
      the numerical escalation of the MEWS system to identify the deteriorating
      patient, instead of their own clinical judgement of the situation. Interestingly,
      the nurses found no difficulty in escalating the patient's care to medical staff
      when the patient presented with a high MEWS score. The difficulty arose when the
      MEWS score was low-the participants found it challenging to authenticate their
      findings. CONCLUSION: this study has identified several confounding factors that
      influence the ways in which nurses assess patient acuity and their response to
      acute deterioration. The information provides a crucial step forward in
      identifying strategies to develop further training.

PMID- 29457946
TI  - The provision of ambulatory systemic anti-cancer therapy.
AB  - This article reflects on the changing nature of the provision of care and
      delivery of ambulatory systemic anti-cancer therapy (SACT) services. It reviews
      the national guidance and looks at ambulatory SACT in terms of patients being
      treated closer to home, i.e. ambulatory care in its truest sense. It considers
      the impact on quality of life for patients receiving treatments at a place of
      their choice. It explores the role of the nurse as an advanced practitioner while
      also examining the safety and delivery of complex regimens ensuring robust
      pathways are in place to deliver care in a safe and standardised way.

PMID- 29457948
TI  - Increasing research capacity and building on the existing evidence base.

PMID- 29457947
TI  - Supporting patients with breast cancer through communication and research.

PMID- 29457949
TI  - NHS compensations payouts: balancing the issues.
AB  - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent
      University, calls for a more balanced view to be taken of issues in the context
      of the debate on the high costs of clinical negligence claims.

PMID- 29457950
TI  - Knowledge and skills of critical care nurses in assisting with intubation.
AB  - Assisting with tracheal intubation is an aspect of clinical practice that
      requires knowledge and skill if the procedure is to be carried out in a timely
      and safe manner. Maintaining this knowledge and skill requires good quality
      education and regular opportunities to practise. These two factors appear to be
      inconsistent in critical care units. This article details an audit performed on a
      large tertiary referral centre critical care unit. It was undertaken in two
      phases: the first was a self-assessment of knowledge and the second was a
      practical assessment of the audit subjects in a simulated setting. Results
      indicated that formal training was inconsistent, as was the opportunity to assist
      with tracheal intubation. These factors may have contributed to the varying
      levels of skill seen in the practical assessment phase. The authors recommend
      devising a standardised training programme to address these issues, which could
      be distributed nationally. High standards need to be instilled early in critical
      care nurses' careers, with regular updates to maintain knowledge and skills.

PMID- 29457951
TI  - From staff nurse to nurse consultant: Spiritual care part 11: Atheism.
AB  - John Fowler, Educational Consultant, explores spiritual care for clinically based
      nurses.

PMID- 29457952
TI  - The need for clinical academic roles.
AB  - Sam Foster, Chief Nurse, Oxford University Hospitals, looks at the importance of
      nurses undertaking academic roles to build on the evidence base for the
      profession to improve patient care.

PMID- 29457954
TI  - Meeting the care needs of a person with dementia who is distressed.

PMID- 29457953
TI  - From nurse to service user: a personal cancer narrative.
AB  - This article presents a snapshot of my experience of being a nurse who became a
      service user with breast cancer. It begins by outlining the Humanization of
      Healthcare Framework ( Todres et al, 2009 ), which is a values-based context that
      can be used to underpin daily care. Generic applications for each of the
      dimensions of the framework are suggested. This framework is then used to
      contextualise my experience of receiving my diagnosis and the ensuing
      chemotherapy. Using examples from my personal narrative, I make some
      recommendations for 'small actions' that can contribute to more humanised and
      person-centred care. I also hope that this narrative prompts reflection by the
      reader and so improves the quality of care given to others.

PMID- 29457955
TI  - A quality project for radiation reduction in the cath lab.
AB  - The radiation exposure in the cath lab of patients, cardiologists, and nurses was
      measured during three consecutive periods of 8 weeks. The first 8 weeks the
      baseline radiation exposure was obtained. In the second period standard
      incidences for coronarography and frame rate were changed, without compromising
      the image quality of the examination. In the third period, a pelvic shield
      covered the lower part of the patient. This pilot quality project demonstrates
      that further significant reduction in radiation exposure of 37% is possible for
      patients. A significant reduction in radiation exposure of 53 and 62% was
      obtained among cardiologists and nurses working in the cath lab, even with the
      already diminished radiation exposure over the last years by better equipment and
      general radioprotection measures.

PMID- 29457958
TI  - Functional variants of p21 gene alter susceptibility to meningioma.

PMID- 29457957
TI  - Synergistic effect of entomopathogenic fungus Fusarium oxysporum extract in
      combination with temephos against three major mosquito vectors.
AB  - Mosquito control using chemical insecticides is facing a major challenge due to
      development of insecticide resistance. Improving the efficiency of existing
      insecticides using synergistic secondary metabolites of biological origin is
      increasingly being researched. Herein, we evaluated the toxicity of Fusarium
      oxysporum extract alone and in binary combinations with temephos, on larvae and
      pupae of Anopheles stephensi, Aedes aegypti and Culex quinquefaciatus. F.
      oxysporum extract was characterized using TLC, FT-IR and GC-MS. After 24 h of
      exposure, the binary combination of temephos + F. oxysporum extract (1:1 ratio)
      was highly toxic to larvae of An. stephensi (LC50: 35.927 MUg/ml), Ae. aegypti
      (LC50: 20.763 MUg/ml) and Cx. quinquefasciatus, (LC50: 51.199 MUg/ml). For pupae
      LC50 values were 38.668, 26.394, and 72.086 MUg/ml, respectively. Histology
      studies of mosquitoes exposed to F. oxysporum extract showed vacuolation in
      epithelium, as well as in adipose, and muscle tissues of larval midgut. Overall,
      our results show that the synergistic combination of temephos and F. oxysporum
      extract is highly effective to control mosquito young instars.

PMID- 29457956
TI  - Gene drives to fight malaria: current state and future directions.
AB  - Self-propagating gene drive technologies have a number of desirable
      characteristics that warrant their development for the control of insect pest and
      vector populations, such as the malaria-transmitting mosquitoes. Theoretically
      easy to deploy and self-sustaining, these tools may be used to generate cost
      effective interventions that benefit society without obvious bias related to
      wealth, age or education. Their species-specific design offers the potential to
      reduce environmental risks and aim to be compatible and complementary with other
      control strategies, potentially expediting the elimination and eradication of
      malaria. A number of strategies have been proposed for gene-drive based control
      of the malaria mosquito and recent demonstrations have shown proof-of-principle
      in the laboratory. Though several technical, ethical and regulatory challenges
      remain, none appear insurmountable if research continues in a step-wise and open
      manner.

PMID- 29457959
TI  - Biosynthesis and applications of prenylquinones.
AB  - Prenylquinones are isoprenoid compounds with a characteristic quinone structure
      and isoprenyl tail that are ubiquitous in almost all living organisms. There are
      four major prenylquinone classes: ubiquinone (UQ), menaquinone (MK),
      plastoquinone (PQ), and rhodoquinone (RQ). The quinone structure and isoprenyl
      tail length differ among organisms. UQ, PQ, and RQ contain benzoquinone, while MK
      contains naphthoquinone. UQ, MK, and RQ are involved in oxidative
      phosphorylation, while PQ functions in photosynthetic electron transfer. Some
      organisms possess two types of prenylquinones; Escherichia coli has UQ8 and MK8,
      and Caenorhabditis elegans has UQ9 and RQ9. Crystal structures of most of the
      enzymes involved in MK synthesis have been solved. Studies on the biosynthesis
      and functions of quinones have advanced recently, including for phylloquinone
      (PhQ), which has a phytyl moiety instead of an isoprenyl tail. Herein, the
      synthesis and applications of prenylquinones are reviewed.

PMID- 29457960
TI  - Phylogenetic Relationships and Acaricidal Effects of Beauveria bassiana Obtained
      from Cattle Farm Soils Against Rhipicephalus microplus.
AB  - The objectives of the present study were to isolate Beauveria bassiana strains
      from cattle farm soils, analyze the phylogenetic relationships among the fungal
      strains isolated from these soils, and determine the acaricidal effect of B.
      bassiana isolates on engorged Rhipicephalus microplus tick strains resistant or
      susceptible to chemical acaricides. Six strains of B. bassiana were obtained and
      isolated from cattle farm soils in the Mexican tropics using the Galleria bait
      method, and their acaricidal effect was assessed against 2 populations of R.
      microplus ("Media Joya" chemical acaricide-resistant strain or "CLAR" chemical
      acaricide-susceptible strain) using the adult immersion test. The BbV03 strain
      produced 86.7% and 60% mortality in resistant and susceptible ticks on day 20,
      respectively, whereas the BbV04 strain produced 66.7% and 53.5% mortality in
      resistant and susceptible ticks on day 20, respectively. The BbV03 and BbV04
      strains reduced egg laying on both R. microplus populations. There was no
      statistical difference in the acaricidal effect of B. bassiana strains among
      chemical acaricide-susceptible or -resistant R. microplus populations ( P >
      0.05). The BbV03 strain was the most virulent against R. microplus with an LC50
      of 2 * 107 and LC99 of 7 * 108 conidia/ml. We found that the 6 B. bassiana
      isolated clustered in the same clade with other previously reported B. bassiana
      strains (from GenBank) but were separated into 3 different sub-clades. This study
      shows that some B. bassiana strains are a promising coadjuvant alternative for
      biological tick control, including tick populations that are resistant to
      chemical acaricides. Beauveria bassiana is present in the pastures of tropic
      cattle farms, and there are genetic variations between B. bassiana strains living
      in this ecosystem that might play an important role in the natural control of R.
      microplus in cattle farm paddocks.

PMID- 29457961
TI  - Examination of 16S-23S rRNA intergenic spacer region (ISR) heterogeneity in a
      population of clinical Streptococcus pneumoniae- a new laboratory epidemiological
      genotyping tool to aid outbreak analysis.

PMID- 29457962
TI  - Genotype Identification and Phylogenetic Analysis of Enterocytozoon bieneusi
      Isolates from Stool Samples of Diarrheic Children.
AB  - Among approximately 14 human-pathogenic microsporidian species, Enterocytozoon
      bieneusi is the most common. It can inhabit the small intestines, causing chronic
      diarrhea and wasting syndrome. Prevalence and genotype data for E. bieneusi in
      humans is available for only a few provinces of China. In the current study, 93
      fecal specimens were collected from diarrheic children in Chongqing. Polymerase
      chain reaction amplification and sequencing of the internal transcribed spacer (
      ITS) region of the E. bieneusi rDNA sequence identified 11 (11.83%) positive
      specimens. Among them, 8 (8.60%) are from patients of ages ranging from 2 mo to 6
      yr old and 3 (3.23%) from patients 7 to 11 yr old. In total, 6 genotypes (4 novel
      genotypes and 2 known genotypes) were identified in this study. Phylogenetic
      analysis showed that all the genotypes identified in the present study belong to
      group 1, which previously has been described as a zoonotic group. This could mean
      these infections were acquired zoonotically, and it may be prudent to warn those
      people having close contact with animals of this potential risk.

PMID- 29457963
TI  - 3-T MR Imaging of Proximal Femur Microarchitecture in Subjects with and without
      Fragility Fracture and Nonosteoporotic Proximal Femur Bone Mineral Density.
AB  - Purpose To determine if 3-T magnetic resonance (MR) imaging of proximal femur
      microarchitecture can allow discrimination of subjects with and without fragility
      fracture who do not have osteoporotic proximal femur bone mineral density (BMD).
      Materials and Methods Sixty postmenopausal women (30 with and 30 without
      fragility fracture) who had BMD T scores of greater than -2.5 in the hip were
      recruited. All subjects underwent dual-energy x-ray absorptiometry to assess BMD
      and 3-T MR imaging of the same hip to assess bone microarchitecture. World Health
      Organization Fracture Risk Assessment Tool (FRAX) scores were also computed. We
      used the Mann-Whitney test, receiver operating characteristics analyses, and
      Spearman correlation estimates to assess differences between groups,
      discriminatory ability with parameters, and correlations among BMD,
      microarchitecture, and FRAX scores. Results Patients with versus without fracture
      showed a lower trabecular plate-to-rod ratio (median, 2.41 vs 4.53,
      respectively), lower trabecular plate width (0.556 mm vs 0.630 mm, respectively),
      and lower trabecular thickness (0.114 mm vs 0.126 mm) within the femoral neck,
      and higher trabecular rod disruption (43.5 vs 19.0, respectively), higher
      trabecular separation (0.378 mm vs 0.323 mm, respectively), and lower trabecular
      number (0.158 vs 0.192, respectively), lower trabecular connectivity (0.015 vs
      0.027, respectively) and lower trabecular plate-to-rod ratio (6.38 vs 8.09,
      respectively) in the greater trochanter (P < .05 for all). Trabecular plate-to
      rod ratio, plate width, and thickness within the femoral neck (areas under the
      curve [AUCs], 0.654-0.683) and trabecular rod disruption, number, connectivity,
      plate-to-rod ratio, and separation within the greater trochanter (AUCs, 0.662
      0.694) allowed discrimination of patients with fracture from control subjects.
      Femoral neck, total hip, and spine BMD did not differ between and did not allow
      discrimination between groups. FRAX scores including and not including BMD
      allowed discrimination between groups (AUCs, 0.681-0.773). Two-factor models (one
      MR imaging microarchitectural parameter plus a FRAX score without BMD) allowed
      discrimination between groups (AUCs, 0.702-0.806). There were no linear
      correlations between BMD and microarchitectural parameters (Spearman rho, -0.198
      to 0.196). Conclusion 3-T MR imaging of proximal femur microarchitecture allows
      discrimination between subjects with and without fragility fracture who have BMD
      T scores of greater than -2.5 and may provide different information about bone
      quality than that provided by dual-energy x-ray absorptiometry. (c) RSNA, 2018.

PMID- 29457964
TI  - Liver Imaging Reporting and Data System: Patient Outcomes for Category 4 and 5
      Nodules.
AB  - Purpose To determine the outcomes after initial therapy in patients with chronic
      liver disease and retrospectively assigned Liver Imaging Reporting and Data
      System (LI-RADS; version 2014) category 4 (LR-4) and 5 (LR-5) nodules at
      gadoxetate disodium-enhanced MR imaging. Materials and Methods In this
      retrospective study, 260 patients with a single LR-4 (n = 132) or LR-5 (n = 128)
      nodule who were assigned a LI-RADS category were included. Patients were
      identified between January 2012 and December 2012, and were initially treated by
      resection, liver transplant, radiofrequency ablation (RFA), or transcatheter
      arterial chemoembolization (TACE) according to the Barcelona Clinic Liver Cancer
      staging system. Follow-up continued until August 31, 2016. The incidences of
      local tumor recurrence (ILRs) and distant tumor recurrence (IDRs) and recurrence
      free survival (RFS) were compared between the LR-4 and LR-5 patients. For each
      category, ILRs, IDRs, and RFS were compared across the four treatments. Results
      LR-5 patients were more frequently treated by surgical resection than LR-4
      patients (72.7% [93 of 128] vs 41.7% [55 of 132], respectively; P < .001), but
      less frequently treated by RFA (19.5% [25 of 128] vs 30.3% [40 of 132],
      respectively; P = .047) and TACE (6.3% [eight of 128] vs 22.0% [29 of 132],
      respectively; P < .001). ILRs and IDRs were not significantly different between
      LR-4 and LR-5 patients according to the type of treatment (0%-48.3% [14 of 29] vs
      0%-25.0% [two of eight], P $ .423; 0%-55.2% [16 of 29] vs 0%-37.5% [three of
      eight], P $ .447, respectively). There was no difference in RFS between the two
      categories (36.3 months vs 41.7 months, respectively; P = .084). Liver transplant
      showed no local or distant tumor recurrence in either category. Resection showed
      higher RFS and lower ILR and IDR than RFA and TACE in both LR-4 and LR-5
      patients. Conclusion Patients with LR-4 nodules had ILRs and IDRs similar to
      patients with LR-5 nodules when stratified by treatment type. RFS was also
      similar between patients with LR-4 and LR-5 nodules. Among the four initial
      treatments, liver transplant and resection showed better local tumor control,
      with longer RFS than RFA or TACE. (c) RSNA, 2018 Online supplemental material is
      available for this article.

PMID- 29457965
TI  - Probing in-plane anisotropy in few-layer ReS2 using low frequency noise
      measurement.
AB  - ReS2, a layered two-dimensional material popular for its in-plane anisotropic
      properties, is emerging as one of the potential candidates for flexible
      electronics and ultrafast optical applications. It is an n-type semiconducting
      material having a layer independent bandgap of 1.55 eV. In this paper we have
      characterized the intrinsic electronic noise level of few-layer ReS2 for the
      first time. Few-layer ReS2 field effect transistor devices show a 1/f nature of
      noise for frequency ranging over three orders of magnitude. We have also observed
      that not only the electrical response of the material is anisotropic; the noise
      level is also dependent on direction. In fact the noise is found to be more
      sensitive towards the anisotropy. This fact has been explained by evoking the
      theory where the Hooge parameter is not a constant quantity, but has a distinct
      power law dependence on mobility along the two-axes direction. The anisotropy in
      1/f noise measurement will pave the way to quantify the anisotropic nature of two
      dimensional (2D) materials, which will be helpful for the design of low-noise
      transistors in future.

PMID- 29457966
TI  - Combined Treatment with Valproic Acid and 5-Aza-2'-Deoxycytidine Synergistically
      Inhibits Human Clear Cell Renal Cell Carcinoma Growth and Migration.
AB  - BACKGROUND Histone acetylation and DNA methylation are important mammalian
      epigenetic modifications that participate in the regulation of gene expression.
      Because dysregulation of histone deacetylase and DNA methyltransferases are
      hallmarks of malignancy, they have become promising therapeutic targets. In this
      study, we explored the anti-tumor activity of valproic acid (VPA), a histone
      deacetylase inhibitor (HDACi) and 5-Aza-2'-deoxycytidine (5-Aza), an inhibitor of
      DNA methyltransferases, on renal cell carcinoma (RCC) cell lines 786-O and 769-P.
      MATERIAL AND METHODS The cell proliferation was detected by xCELLigence RTCA DP
      Instrument, viability by CCK8 assay, cell apoptosis and cell cycle by flow
      cytometry, and cell migration by wound healing assay, Transwell assay and
      xCELLigence RTCA DP Instrument. RESULTS We discovered that VPA and 5-Aza could
      individually induce decreased viability and have an inhibitory effect on the
      proliferation of 786-O and 769-P cells. This anti-growth effect was more
      pronounced when the cells were treated with both VPA and 5-Aza. The combination
      of VPA and 5-Aza also elicited more apoptosis and produced more cell cycle arrest
      in the G1 phase for both cell lines. On the other hand, treatment of RCC cells
      with VPA, 5-Aza, or a combination of both resulted in slow wound healing and
      impaired migration. CONCLUSIONS These findings clearly demonstrated that VPA
      combined with 5-Aza could significantly increase anti-RCC effects by inhibiting
      cellular proliferation, inducing apoptosis, promoting cell cycle arrest and
      prohibiting the migration of human RCC cells.

PMID- 29457967
TI  - DNA damage and genomic instability among workers formerly and currently exposed
      to asbestos.
AB  - Objectives Despite an asbestos ban in the European Union, exposure to asbestos
      still represents an occupational risk. Biomarkers of DNA damage and genomic
      instability in groups exposed to asbestos may contribute to the identification of
      subgroups/subjects at higher risk. Methods A cross-sectional study was conducted
      on 468 male individuals (80 working in occupational settings with potential
      exposure to asbestos fibers, 202 retired workers with past exposure, and 186 non
      exposed controls) to compare genomic instability, cell proliferation and
      differentiation level using the non-invasive micronucleus buccal cytome assay.
      Data on demographic variables, lifestyle, and occupational history were collected
      with a standardized questionnaire. Micronuclei (MN) and other biomarkers of DNA
      damage and genomic instability were scored in a minimum of 2000/1000 cells per
      individual, respectively. Results Univariate and multivariate analysis showed
      opposite associations of MN frequency with current and former exposure. Compared
      to unexposed controls, workers with current potential exposure to asbestos had
      55% lower MN frequency [95% confidence interval (CI) 71-29%, P<0.001] while those
      with past exposure had 34% higher MN frequency (95% CI 1-77%, P<0.001). The
      frequency of cells with condensed chromatin and binucleated cells was elevated
      among formerly exposed workers. The multivariate analysis did not reveal any
      actual confounders, although lower MN frequency was observed among subjects
      eating fresh fruit or vegetables every day or taking vitamin supplements.
      Conclusions Active workers with potential exposure to asbestos fibers did not
      show increased genomic damage. On the contrary, workers exposed in the past
      experienced a persistently elevated genomic instability, which may be used for
      risk assessment at subgroup or individual level.

PMID- 29457969
TI  - An evaluation of the operational model when applied to quantify functional
      selectivity.
AB  - BACKGROUND AND PURPOSE: Functional selectivity describes the ability of ligands
      to differentially regulate multiple signalling pathways when coupled to a single
      receptor, and the operational model is commonly used to analyse these data. Here,
      we assess the mathematical properties of the operational model and evaluate the
      outcomes of fixing parameters on model performance. EXPERIMENTAL APPROACH: The
      operational model was evaluated using both a mathematical identifiability
      analysis and simulation. KEY RESULTS: Mathematical analysis revealed that the
      parameters R0 and KE were not independently identifiable which can be solved by
      considering their ratio, tau. The ratio parameter, tau, was often imprecisely
      estimated when only functional assay data were available and generally only the
      transduction coefficient R ( tauKA) could be estimated precisely. The general
      operational model (that includes baseline and the Hill coefficient) required
      either the parameters Em or KA to be fixed. The normalization process largely
      cancelled out the mean error of the calculated Deltalog (R) caused by fixing
      these parameters. From this analysis, it was determined that we can avoid the
      need for a full agonist ligand to be included in an experiment to determine
      Deltalog (R). CONCLUSION AND IMPLICATIONS: This analysis has provided a ready-to
      use understanding of current methods for quantifying functional selectivity. It
      showed that current methods are generally tolerant to fixing parameters. A new
      method was proposed that removes the need for including a high efficacy ligand in
      any given experiment, which allows application to large-scale screening to
      identify compounds with desirable features of functional selectivity.

PMID- 29457970
TI  - Synthesis of Palladium Nanoscale Octahedra through a One-Pot, Dual-Reductant
      Route and Kinetic Analysis.
AB  - Shape-controlled synthesis of colloidal metal nanocrystals has traditionally
      relied on the use of an approach that involves the reduction of a metal precursor
      by a single reductant. Once the concentration of atoms surpasses supersaturation,
      they will undergo homogeneous nucleation to generate nuclei and then seeds,
      followed by further growth into nanocrystals. In general, it is a grand challenge
      to optimize such an approach because the kinetic requirement for nucleation tends
      to be drastically different from what is needed to guide the growth process. In
      this work, we overcome this difficulty by switching to a dual-reductant approach,
      in which both strong and weak reductants are added into the same reaction
      solution. By controlling their amounts to program the reduction kinetics, the
      strong reductant only regulates the homogeneous nucleation process to generate
      the desired seeds, and once consumed, the weak reductant takes over to control
      the growth pattern and thereby the shape of the resulting nanocrystals.

PMID- 29457968
TI  - In vitro and in vivo effects of MK2206 and chloroquine combination therapy on
      endometriosis: autophagy may be required for regrowth of endometriosis.
AB  - BACKGROUND AND PURPOSE: A high recurrence rate after medical treatment is a major
      clinical problem for patients with endometriosis. Here, we have evaluated the in
      vitro effects of combined treatment with MK2206 (an AKT inhibitor) + chloroquine
      on cell growth and regrowth of endometriotic stromal cells and the in vivo
      effects on endometriotic implants in a mouse xenograft model of endometriosis.
      EXPERIMENTAL APPROACH: We evaluated the effects of autophagy inhibition by
      knockdown of the ATG13, Beclin-1 and ATG12 genes and pharmacological agents
      (chloroquine, bafilomycin A1 or 3-methyalanine) individually and in combination
      with MK2206 on cell growth and/or cell regrowth of endometriotic stromal cells in
      vitro. Furthermore, we evaluated treatment with MK2206 + chloroquine on
      endometriotic implants in a mouse xenograft model of endometriosis. KEY RESULTS:
      Combined treatment with MK2206 and chloroquine markedly reduced cell growth and
      regrowth after discontinuation of treatment in endometriotic stromal cells
      compared with cells treated with either drug alone. Autophagy inhibition by
      ATG13, Beclin-1 or ATG12 gene knockdown only affected regrowth of endometriotic
      stromal cells, but not endometrial stromal cells from the same patients, after a
      72 h discontinuation of the combined treatment. Furthermore, combined treatment
      reduced the size of endometriotic implants, whereas no effects on endometriotic
      implants treated with either drug alone were observed in a mouse xenograft model
      of endometriosis. CONCLUSIONS AND IMPLICATIONS: The present findings suggest that
      a novel strategy for treatment of endometriosis may involve decreasing the number
      of endometriotic cells that can survive treatment and then preventing regrowth by
      autophagy inhibition.

PMID- 29457971
TI  - Visible-Light Photocatalysis: Does It Make a Difference in Organic Synthesis?
AB  - Visible-light photocatalysis has evolved over the last decade into a widely used
      method in organic synthesis. Photocatalytic variants have been reported for many
      important transformations, such as cross-coupling reactions, alpha-amino
      functionalizations, cycloadditions, ATRA reactions, or fluorinations. To help
      chemists select photocatalytic methods for their synthesis, we compare in this
      Review classical and photocatalytic procedures for selected classes of reactions
      and highlight their advantages and limitations. In many cases, the photocatalytic
      reactions proceed under milder reaction conditions, typically at room
      temperature, and stoichiometric reagents are replaced by simple oxidants or
      reductants, such as air, oxygen, or amines. Does visible-light photocatalysis
      make a difference in organic synthesis? The prospect of shuttling electrons back
      and forth to substrates and intermediates or to selectively transfer energy
      through a visible-light-absorbing photocatalyst holds the promise to improve
      current procedures in radical chemistry and to open up new avenues by accessing
      reactive species hitherto unknown, especially by merging photocatalysis with
      organo- or metal catalysis.

PMID- 29457972
TI  - A Stable Metal-Organic Framework Featuring a Local Buffer Environment for Carbon
      Dioxide Fixation.
AB  - A majority of metal-organic frameworks (MOFs) fail to preserve their physical and
      chemical properties after exposure to acidic, neutral, or alkaline aqueous
      solutions, therefore limiting their practical applications in many areas. The
      strategy demonstrated herein is the design and synthesis of an organic ligand
      that behaves as a buffer to drastically boost the aqueous stability of a porous
      MOF (JUC-1000), which maintains its structural integrity at low and high pH
      values. The local buffer environment resulting from the weak acid-base pairs of
      the custom-designed organic ligand also greatly facilitates the performance of
      JUC-1000 in the chemical fixation of carbon dioxide under ambient conditions,
      outperforming a series of benchmark catalysts.

PMID- 29457973
TI  - Pyrazole-Tetrazole Hybrid with Trinitromethyl, Fluorodinitromethyl, or
      (Difluoroamino)dinitromethyl Groups: High-Performance Energetic Materials.
AB  - High-nitrogen-content compounds have attracted great scientific interest and
      technological importance because of their unique energy content, and they find
      diverse applications in many fields of science and technology. Understanding of
      structure-property relationship trends and how to modify them is of paramount
      importance for their further improvement. Herein, the installation of oxygen-rich
      modules, C(NO2 )3 , C(NO2 )2 F, or C(NO2 )2 NF2 , into an endothermic framework,
      that is, the combination of a nitropyrazole unit and tetrazole ring, is used as a
      way to design novel energetic compounds. Density, oxygen balance, and enthalpy of
      formation are enhanced by the presence of these oxygen-containing units. The
      structures of all compounds were confirmed by XRD. For crystal packing analysis,
      it is proposed to use new criterion, DeltaOED , that can serve as a measure of
      the tightness of molecular packing upon crystal formation. Overall, the materials
      show promising detonation and propulsion parameters.

PMID- 29457974
TI  - A Multi-Omics Analysis of Glycine max Leaves Reveals Alteration in Flavonoid and
      Isoflavonoid Metabolism Upon Ethylene and Abscisic Acid Treatment.
AB  - Phytohormones are central to plant growth and development. Despite the
      advancement in our knowledge of hormone signaling, downstream targets, and their
      interactions upon hormones action remain largely fragmented, especially at the
      protein and metabolite levels. With an aim to get new insight into the effects of
      two hormones, ethylene (ET) and abscisic acid (ABA), this study utilizes an
      integrated proteomics and metabolomics approach to investigate their individual
      and combined (ABA+ET) signaling in soybean leaves. Targeting low-abundance
      proteins, our previously established protamine sulfate precipitation method was
      applied, followed by label-free quantification of identified proteins. A total of
      4129 unique protein groups including 1083 differentially modulated in one
      (individual) or other (combined) treatments were discerned. Functional annotation
      of the identified proteins showed an increased abundance of proteins related to
      the flavonoid and isoflavonoid biosynthesis and MAPK signaling pathway in
      response to ET treatment. HPLC analysis showed an accumulation of isoflavones
      (genistin, daidzein, and genistein) upon ET treatment, in agreement with the
      proteomics results. A metabolome analysis assigned 79 metabolites and further
      confirmed the accumulation of flavonoids and isoflavonoids in response to ET. A
      potential cross-talk between ET and MAPK signaling, leading to the accumulation
      of flavonoids and isoflavonoids in soybean leaves is suggested.

PMID- 29457975
TI  - Fluorescent DNA Probing Nanoscale MnO2: Adsorption, Dissolution by Thiol, and
      Nanozyme Activity.
AB  - Manganese dioxide (MnO2) is an interesting material due to its excellent
      biocompatibility and magnetic properties. Adsorption of DNA to MnO2 is
      potentially of interest for drug delivery and sensing applications. However,
      little fundamental understanding is known about their interactions. In this work,
      carboxyfluorescein (FAM)-labeled DNA oligonucleotides were used to explore the
      effect of salt concentration, pH, and DNA sequence and length for adsorption by
      MnO2, and comparisons were made with graphene oxide (GO). The DNA desorbs from
      MnO2 by free inorganic phosphate, while it desorbs from GO by adenosine and urea.
      Therefore, DNA is mainly adsorbed on MnO2 through its phosphate backbone, and DNA
      has a stronger affinity on MnO2 than on GO based on a salt-shock assay. At the
      same time, DNA was used to study the effect of thiol containing compounds on the
      dissolution of MnO2. Adsorbed DNA was released from MnO2 after its dissolution by
      thiol, but not from other metal oxides with lower solubility such as CeO2, TiO2,
      and Fe3O4. DNA-functionalized MnO2 was then used for detecting glutathione (GSH)
      with a detection limit of 383 nM. Finally, DNA was found to inhibit the
      peroxidase-like activity of MnO2. This study has offered many fundamental
      insights into the interaction between MnO2 and two important biomolecules: DNA
      and thiol-containing compounds.

PMID- 29457976
TI  - Radiosynthesis and in Vivo Evaluation of [11C]MPC-6827, the First Brain Penetrant
      Microtubule PET Ligand.
AB  - Abnormalities of microtubules (MTs) are implicated in the pathogenesis of many
      CNS diseases. Despite the potential of an MT imaging agents, no PET ligand is
      currently available for in vivo imaging of MTs in the brain. We radiolabeled
      [11C]MPC-6827, a high affinity MTA, and demonstrated its specific binding in rat
      and mice brain using PET imaging. Our experiments show that [11C]MPC-6827 has
      specific binding to MT in brain, and it is the first MT-binding PET ligand.

PMID- 29457978
TI  - Size-Dependent Thermodynamics and Kinetics of Adsorption on Nanoparticles: A
      Theoretical and Experimental Study.
AB  - Owing to their excellent adsorption properties compared with those of the
      corresponding bulk materials, nanoparticles have been widely applied in many
      fields. Their properties depend on the thermodynamics and kinetics of adsorption,
      which depend on the particle size. In this paper, we present universal theories
      of the thermodynamics and kinetics for nanoadsorption that have been developed
      over the past few years. Theoretically, we have derived relationships between the
      adsorption thermodynamic properties and the particle size, as well as those
      between the adsorption kinetic parameters and the particle size. Moreover, we
      discuss the regularities and mechanisms of influence of the particle size on the
      thermodynamics and kinetics of adsorption. Experimentally, taking the adsorption
      of methyl orange on nano-CeO2 in aqueous solution as a system, we have studied
      the size-dependent thermodynamics and kinetics of the system, and the size
      dependences were confirmed to be consistent with the theoretical relationships.
      The results indicate that particle size has a significant effect on the
      thermodynamic properties and kinetic parameters of adsorption: with decreasing
      particle size of nano-CeO2, the adsorption equilibrium constant K? and the
      adsorption rate constant k increase, while the molar Gibbs free energy of
      adsorption Deltaads Gm?, the molar adsorption entropy Deltaads Sm?, the molar
      adsorption enthalpy Deltaads Hm?, the adsorption activation energy Ea, and the
      adsorption pre-exponential factor A all decrease. Indeed, ln K?, Deltaads Gm?,
      Deltaads Sm?, Deltaads Hm?, ln  k, Ea, and ln  A are each linearly related to the
      reciprocal of particle size. Furthermore, thermodynamically, Deltaads Gm? and ln 
      K? are influenced by the molar surface area and the difference in surface
      tensions, Deltaads Sm? is influenced by the molar surface area and the difference
      in temperature coefficients of surface tension, and Deltaads Hm? is influenced by
      the molar surface area, the difference in surface tensions, and the difference in
      temperature coefficients of surface tension. Kinetically, Ea is influenced by the
      partial molar surface enthalpy of the nanoadsorbent, ln  A is influenced by the
      partial molar surface entropy, and ln  k is influenced by the partial molar
      surface Gibbs energy. The theories can quantitatively describe adsorption
      behavior on nanoparticles, explain the regularities and mechanisms of influence
      of particle size, and provide guidance for the research and application of
      nanoadsorption.

PMID- 29457977
TI  - The Single-Molecule Centroid Localization Algorithm Improves the Accuracy of
      Fluorescence Binding Assays.
AB  - Here, we demonstrate that the use of the single-molecule centroid localization
      algorithm can improve the accuracy of fluorescence binding assays. Two major
      artifacts in this type of assay, i.e., nonspecific binding events and optically
      overlapping receptors, can be detected and corrected during analysis. The
      effectiveness of our method was confirmed by measuring two weak biomolecular
      interactions, the interaction between the B1 domain of streptococcal protein G
      and immunoglobulin G and the interaction between double-stranded DNA and the Cas9
      RNA complex with limited sequence matches. This analysis routine requires little
      modification to common experimental protocols, making it readily applicable to
      existing data and future experiments.

PMID- 29457979
TI  - Samholides, Swinholide-Related Metabolites from a Marine Cyanobacterium cf.
      Phormidium sp.
AB  - Cancer cell cytotoxicity was used to guide the isolation of nine new swinholide
      related compounds, named samholides A-I (1-9), from an American Samoan marine
      cyanobacterium cf. Phormidium sp. Their structures were determined by extensive
      analysis of 1D and 2D NMR spectroscopic data. The new compounds share an unusual
      20-demethyl 44-membered lactone ring composed of two monomers, and they
      demonstrate structural diversity arising from geometric isomerization of double
      bonds, sugar units with unique glyceryl moieties and varied methylation patterns.
      All of the new samholides were potently active against the H-460 human lung
      cancer cell line with IC50 values ranging from 170 to 910 nM. The isolation of
      these new swinholide-related compounds from a marine cyanobacterium reinvigorates
      questions concerning the evolution and biosynthetic origin of these natural
      products.

PMID- 29457980
TI  - Probing the Chemistry of Adhesion between a 316L Substrate and Spin-on-Glass
      Coating.
AB  - Hydrogen silsesquioxane ([HSiO3/2] n)-based "spin-on-glass" has been deposited on
      a 316L substrate and cured in Ar/H2 gas atmosphere at 600  degrees C to form a
      continuous surface coating with submicrometer thickness. The coating
      functionality depends primarily on the adhesion to the substrate, which is
      largely affected by the chemical interaction at the interface between the coating
      and the substrate. We have investigated this interface by transmission electron
      microscopy and electron energy loss spectroscopy. The analysis identified a 5-10
      nm thick interaction zone containing signals from O, Si, Cr, and Fe. Analysis of
      the energy loss near edge structure of the present elements identified
      predominantly signal from [SiO4]4- units together with Fe2+, Cr2+, and traces of
      Cr3+. High-resolution transmission electron microscopy images of the interface
      region confirm a crystalline Fe2SiO4 interfacial region. In agreement with
      computational thermodynamics, it is proposed that the spin-on-glass forms a
      chemically bonded silicate-rich interaction zone with the substrate. It was
      further suggested that this zone is composed of a corundum-type oxide at the
      substrate surface, followed by an olivine-structure intermediate phase and a
      spinel-type oxide in the outer regions of the interfacial zone.

PMID- 29457981
TI  - Reversible Surface Engineering via Nitrone-Mediated Radical Coupling.
AB  - Efficient and simple polymer conjugation reactions are critical for introducing
      functionalities on surfaces. For polymer surface grafting, postpolymerization
      modifications are often required, which can impose a significant synthetic
      hurdle. Here, we report two strategies that allow for reversible surface
      engineering via nitrone-mediated radical coupling (NMRC). Macroradicals stemming
      from the activation of polymers generated by copper-mediated radical
      polymerization are grafted via radical trapping with a surface-immobilized
      nitrone or a solution-borne nitrone. Since the product of NMRC coupling features
      an alkoxyamine linker, the grafting reactions can be reversed or chain insertions
      can be performed via nitroxide-mediated polymerization (NMP). Poly( n-butyl
      acrylate) ( Mn = 1570 g.mol-1, D = 1.12) with a bromine terminus was reversibly
      grafted to planar silicon substrates or silica nanoparticles as successfully
      evidenced via X-ray photoelectron spectroscopy (XPS), time-of-flight secondary
      ion mass spectrometry, and grazing angle attenuated total reflection Fourier
      transform infrared spectroscopy (GAATR-FTIR). NMP chain insertions of styrene are
      evidenced via GAATR-FTIR. On silica nanoparticles, an NMRC grafting density of
      close to 0.21 chains per nm2 was determined by dynamic light scattering and
      thermogravimetric analysis. Concomitantly, a simple way to decorate particles
      with nitroxide radicals with precise control over the radical concentration is
      introduced. Silica microparticles and zinc oxide, barium titanate, and silicon
      nanoparticles were successfully functionalized.

PMID- 29457982
TI  - Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton's Tyrosine
      Kinase Inhibitor in Early Clinical Development.
AB  - Bruton's tyrosine kinase (Btk) is a nonreceptor cytoplasmic tyrosine kinase
      involved in B-cell and myeloid cell activation, downstream of B-cell and Fcgamma
      receptors, respectively. Preclinical studies have indicated that inhibition of
      Btk activity might offer a potential therapy in autoimmune diseases such as
      rheumatoid arthritis and systemic lupus erythematosus. Here we disclose the
      discovery and preclinical characterization of a potent, selective, and
      noncovalent Btk inhibitor currently in clinical development. GDC-0853 (29)
      suppresses B cell- and myeloid cell-mediated components of disease and
      demonstrates dose-dependent activity in an in vivo rat model of inflammatory
      arthritis. It demonstrates highly favorable safety, pharmacokinetic (PK), and
      pharmacodynamic (PD) profiles in preclinical and Phase 2 studies ongoing in
      patients with rheumatoid arthritis, lupus, and chronic spontaneous urticaria. On
      the basis of its potency, selectivity, long target residence time, and
      noncovalent mode of inhibition, 29 has the potential to be a best-in-class Btk
      inhibitor for a wide range of immunological indications.

PMID- 29457984
TI  - Cardio-oncology: the role of advanced echocardiography in cancer patients.
AB  - INTRODUCTION: Cardio-oncology is a rapidly growing field aimed at improving the
      quality of care of cancer patients by preventing and monitoring cardiovascular
      complications resulting from cancer treatment. Cardiac imaging, and in
      particular, transthoracic echocardiography, plays an essential?role in the
      baseline assessment and serial follow-up of cardio-oncology patients. Areas
      covered: This review article discusses the role of cardiac imaging with a focus
      on advanced echocardiography for the detection and management of cancer therapy
      related cardiovascular complications, in particular, left ventricular dysfunction
      and heart failure. Expert commentary: While traditional imaging based assessment
      of left ventricular ejection fraction still has its place in cardiac monitoring,
      more advanced echocardiographic modalities, in particular, myocardial deformation
      imaging with speckle tracking strain analysis, show great potential for detecting
      early signs of cardiotoxicity. Larger studies are needed to determine both the
      clinical role of strain measurement in influencing initiation of cardioprotective
      agents and its prognostic value in long term outcome.

PMID- 29457985
TI  - Tooth-level versus patient-level.

PMID- 29457983
TI  - Antimycobacterial effect of IFNG (interferon gamma)-induced autophagy depends on
      HMOX1 (heme oxygenase 1)-mediated increase in intracellular calcium levels and
      modulation of PPP3/calcineurin-TFEB (transcription factor EB) axis.
AB  - IFNG (interferon gamma)-induced autophagy plays an important role in the
      elimination of intracellular pathogens, such as Mycobacterium tuberculosis (Mtb).
      However, the signaling cascade that leads to the increase in autophagy flux in
      response to IFNG is poorly defined. Here, we demonstrate that HMOX1 (heme
      oxygenase 1)-generated carbon monoxide (CO) is required for the induction of
      autophagy and killing of Mtb residing in macrophages in response to
      immunomodulation by IFNG. Interestingly, IFNG exposure of macrophages induces an
      increase in intracellular calcium levels that is dependent on HMOX1 generated CO.
      Chelation of intracellular calcium inhibits IFNG-mediated autophagy and
      mycobacterial clearance from macrophages. Moreover, we show that IFNG-mediated
      increase in intracellular calcium leads to activation of the phosphatase
      calcineurin (PPP3), which dephosphorylates the TFEB (transcription factor EB) to
      induce autophagy. PPP3-mediated activation and nuclear translocation of TFEB are
      critical in IFNG-mediated mycobacterial trafficking and survival inside the
      infected macrophages. These findings establish that IFNG utilizes the PPP3-TFEB
      signaling axis for inducing autophagy and regulating mycobacterial growth. We
      believe this signaling axis could act as a therapeutic target for suppression of
      growth of intracellular pathogens.

PMID- 29457986
TI  - Effect of oral stimulation on feeding performance and weight gain in preterm
      neonates: a randomised controlled trial.
AB  - BACKGROUND: In preterm infants, oral stimulation enhances muscle tone and
      movement which facilitates normal oral motor developmental patterns improving
      oral feeding performance. AIM: To study the effects on feeding performance,
      transition to independent oral feeding, weight gain and length of hospital stay
      of an oral stimulation programme in preterm neonates. STUDY DESIGN: This
      randomised controlled trial was conducted in a tertiary care teaching hospital
      over a period of 10 months. Altogether, 102 preterm neonates (30-34 weeks
      gestation) were randomised into the intervention group (oro-motor stimulation for
      5 min twice a day, n = 51) or the control group (routine care only, n = 51). The
      primary outcome measures were feeding performance, and transition period to reach
      independent oral feeding. RESULTS: There was better feeding performance (overall
      intake and rate of milk transfer), shorter transition to independent oral
      feeding, better weight gain and shorter length of hospital stay in the
      intervention group (p < 0.001). CONCLUSIONS: Oral stimulation improves feeding
      performance, weight gain rate and reduces hospital stay in preterm neonates born
      between 30 and 34 weeks of gestation. [Trial registration number:
      CTRI/2017/05/008630].

PMID- 29457987
TI  - The Rap2c GTPase facilitates B cell receptor-induced reorientation of the
      microtubule-organizing center.
AB  - When B lymphocytes encounter antigen-bearing surfaces, B-cell receptor (BCR)
      signaling initiates remodeling of the F-actin network and reorientation of the
      microtubule-organizing center (MTOC) towards the antigen contact site. We have
      previously shown that the Rap1 GTPase, an evolutionarily conserved regulator of
      cell polarity, is essential for these processes and that Rap1-regulated actin
      remodeling is required for MTOC polarization. The role of Rap2 proteins in
      establishing cell polarity is not well understood. We now show that depleting
      Rap2c, the only Rap2 isoform expressed in the A20 B-cell line, impairs BCR
      induced MTOC reorientation as well as the actin remodeling that supports MTOC
      polarization. Thus Rap1 and Rap2 proteins may have similar but non-redundant
      functions in coupling the BCR to MTOC polarization.

PMID- 29457989
TI  - Propylthiouracil-induced anti-neutrophil cytoplasmic antibody-associated
      vasculitis mimicking Kawasaki disease.
AB  - Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is rare
      in children and is characterised as necrotising vasculitis predominantly
      affecting small and medium-sized vessels. Propylthiouracil (PTU), an antithyroid
      drug, has been implicated in drug-induced AAV. In contrast, Kawasaki disease (KD)
      is a common systemic vasculitis, typically observed in children, which affects
      the medium-sized vessels, including the coronary arteries. An 11-year-old girl
      who developed AAV while receiving PTU therapy for Graves' disease is described.
      She was admitted to hospital following a 2-day history of fever, cervical
      adenopathy, cheilitis and papular rash, 3 weeks after an increase in the PTU
      dose. Despite discontinuation of PTU and the administration of intravenous
      antibiotic therapy, her clinical condition deteriorated and over the next 2 days
      she developed severe diarrhoea, conjunctival injection and swelling and redness
      of the right index finger. Additional findings included liver dysfunction,
      hydrops of the gallbladder, coagulopathy and urine abnormalities, suggesting
      glomerulonephritis. She met the diagnostic criteria for KD and received
      intravenous immunoglobulin (IVIG) combined with prednisolone, with rapid
      resolution of clinical and laboratory parameters. Peeling of the right index
      fingertip became evident on Day 12 of admission. Serial ultrasound cardiography
      demonstrated no evidence of cardiac involvement. A high titre of myeloperoxidase
      ANCA was detected in the patient's serum on admission, and the titre decreased
      during the convalescent stage. This case demonstrates that children with PTU
      associated AAV may present with clinical features mimicking KD, and that IVIG
      along with corticosteroid therapy may be effective in treating patients with drug
      induced severe systemic AAV.

PMID- 29457990
TI  - Learning from Fukushima - nuclear power in East Asia.

PMID- 29457988
TI  - Looking through Staphylococcus pseudintermedius infections: Could SpA be
      considered a possible vaccine target?

PMID- 29457991
TI  - Protection of sheep by vaccination against experimental challenge with Leptospira
      borgpetersenii serovar Hardjo and L. interrogans serovar Pomona.
AB  - AIMS: To evaluate a multivalent leptospiral and clostridial vaccine for
      prevention of renal colonisation and urinary shedding in sheep, following
      experimental challenge with New Zealand strains of Leptospira borgpetersenii
      serovar Hardjo type Hardjobovis and L. interrogans serovar Pomona. METHODS: Two
      separate but similarly designed studies were conducted. In both studies, Romney
      cross lambs, aged 9-11 weeks, were randomly allocated to a vaccinated group and a
      control group. Vaccinated lambs each received two 1.5-mL S/C doses of a
      multivalent leptospiral and clostridial vaccine, 4 weeks apart, and animals in
      the control groups received the same dose of saline. Groups of 12 vaccinated and
      12 control lambs were randomly selected in each study for challenge with serovars
      Hardjo or Pomona. Challenge was initiated 16 weeks following the second
      vaccination with three daily doses of live leptospires by intranasal and
      conjunctival routes. Following challenge, urine samples were collected weekly for
      6 weeks, for dark field microscopy and leptospiral culture; 6 weeks after
      challenge the lambs were slaughtered and kidneys collected for leptospiral
      culture. RESULTS: In lambs challenged with serovar Hardjo, 8/12 unvaccinated
      lambs had >=1 urine or kidney sample that was positive for leptospires following
      culture, compared with 0/12 lambs in the vaccinated group (p=0.001). In lambs
      challenged with serovar Pomona, 9/12 unvaccinated lambs had >=1 urine or kidney
      sample that was positive following culture, compared with 0/12 lambs in the
      vaccinated group (p<0.001). Prevention of renal colonisation and urinary
      shedding, expressed as the prevented fraction, was 100 (95% CI=61.7-100)% and 100
      (95% CI=68.3-100)% against challenge with serovars Hardjo and Pomona,
      respectively, at 4 months after vaccination. CONCLUSIONS AND CLINICAL RELEVANCE:
      Use of a multivalent leptospiral and clostridial vaccine demonstrated protection
      against challenge from New Zealand strains of serovars of Hardjo and Pomona 4
      months after vaccination in lambs first vaccinated at 9-11 weeks of age. Further
      studies are required to assess the duration of immunity against challenge in
      sheep.

PMID- 29457992
TI  - Ground ultra low volume (ULV) space spray applications for the control of wild
      sand fly populations (Psychodidae: Phlebotominae) in Europe.
AB  - The Phlebotomus sand flies are considered an important vector of both canine and
      human leishmaniasis. Current measures for sand fly control include mostly indoor
      interventions, such as residual spraying of dwellings (IRS) to target endophilic
      sand fly species with very limited number of vector control tools for outdoor
      interventions against exophilic sand flies. In this study we investigated the
      efficacy of ground ultra low volume (ULV) space spray applications of a
      deltamethrin based product against field populations of P. perfiliewi, a major
      nuisance and pathogen-transmitting sand fly species of the Mediterranean Basin.
      Sand fly flight activity patterns and flight height preference within candidate
      treatment sites (kennels) were determined prior to treatments in order to
      optimize the timing and application parameters of the spray applications. On
      average there was a distinct activity peak between 20.00-22.00 h for both male
      and female P. perfiliewi with more than 45% and 30% of the population sampled
      occurring between 20.00-21.00 h and 21.00-22.00 h, respectively. No significant
      difference was observed in sand fly numbers from sticky traps placed at 0.5 up to
      1.5 m height. However, there was a significant decrease in sand fly numbers at 2
      m indicating a preference of sand flies to fly below 2 m. The low and high
      application rate of deltamethrin resulted in mean sand fly population decrease of
      18 and 66%, respectively between pre-and post-treatment trap nights. The percent
      mean population change in the untreated control area was a positive number (30%)
      indicating that there was an increase in numbers of sand flies trapped between
      pre- and post-treatment nights. The results of this study provide strong evidence
      that ground ULV space spray applications when applied properly can result in
      significant sand fly control levels, even in a heavily infested sand fly
      environment such as the kennel sites used in this study.

PMID- 29457993
TI  - Leptospira seroprevalence in animals in the Caribbean region: A systematic
      review.
AB  - This systematic review summarises the data published on the Leptospira
      seroprevalence, serovar diversity and distribution among animal species in the
      Caribbean region. Following Preferred Reporting Items for Systematic Reviews and
      Meta-Analysis (PRISMA) guidelines, and checklist, relevant articles were
      identified and data were extracted and recorded. The review provided Leptospira
      seroprevalence data from 16 Caribbean islands (Barbados, Trinidad, Grenada,
      Puerto Rico, Saint Croix, St. Kitts and Nevis, Jamaica, Antigua, Carriacou,
      Dominica, Guadalupe, Martinique, Monserrat, St. Lucia, St. Maarten, and St.
      Vincent) in a variety of animal species. Reviewing the literature highlighted the
      limited amount of data available from limited number of islands. Many of the
      studies conducted have recorded seroprevalences based on variable and small
      samples sizes. Besides, serovar panels used for MAT were not consistent between
      studies. The review indicates that the Leptospira exposure in a given geographic
      location may change with time and climatic and environmental conditions, and
      highlights the need to conduct continual surveillance in tropical countries where
      the climate supports the survival of Leptospira in the environment. Specific
      attention must be given to standardization of MAT panels and protocols and
      providing training across laboratories involved in testing. Further, animal and
      environment testing to isolate and identify circulating Leptospira spp. in a
      geographic region must actively be pursued. This knowledge is important to
      implement geographically specific control programs, as risk factors of Leptospira
      transmission is favoured by various factors such as change in climatic
      conditions, urbanization, encroachment of wildlife inhabitation, import/export of
      animals, increase in adventure travel, and water related recreational activities.

PMID- 29457994
TI  - Uric acid and allopurinol aggravate absence epileptic activity in Wistar Albino
      Glaxo Rijswijk rats.
AB  - Uric acid has a role in several physiological and pathophysiological processes.
      For example, uric acid may facilitate seizure generalization while reducing uric
      acid level may evoke anticonvulsant/antiepileptic effects. Allopurinol blocks the
      activity of xanthine oxidase, by which allopurinol inhibits catabolism of
      hypoxanthine to xanthine and uric acid and, as a consequence, decreases the level
      of uric acid. Although the modulation of serum uric acid level is a widely used
      strategy in the treatment of certain diseases, our knowledge regarding the
      effects of uric acid on epileptic activity is far from complete. Thus, the main
      aim of this study was the investigation of the effect of uric acid on absence
      epileptic seizures (spike-wave discharges: SWDs) in a model of human absence
      epilepsy, the Wistar Albino Glaxo/Rijswijk (WAG/Rij) rat. We investigated the
      influence of intraperitoneally (i.p.) injected uric acid (100 mg/kg and 200
      mg/kg), allopurinol (50 mg/kg and 100 mg/kg), a cyclooxygenase 1 and 2 (COX-1 and
      COX-2) inhibitor indomethacin (10 mg/kg) and inosine (500 mg/kg) alone and the
      combined application of allopurinol (50 mg/kg) with uric acid (100 mg/kg) or
      inosine (500 mg/kg) as well as indomethacin (10 mg/kg) with uric acid (100 mg/kg)
      and inosine (500 mg/kg) with uric acid (100 mg/kg) on absence epileptic activity.
      We demonstrated that both uric acid and allopurinol alone significantly increased
      the number of SWDs whereas indomethacin abolished the uric acid-evoked increase
      in SWD number. Our results suggest that uric acid and allopurinol have
      proepileptic effects in WAG/Rij rats.

PMID- 29457995
TI  - Translation and validation of the Transition Readiness Assessment Questionnaire
      (TRAQ).
AB  - OBJECTIVE: To translate and validate the Brazilian Portuguese version of the
      Transition Readiness Assessment Questionnaire in a population of adolescents and
      young adults with chronic rheumatologic disorders. This questionnaire evaluates
      the patient's readiness for making the transition from the pediatric health
      service to adult care. METHODS: The four-phase methodology for the translation
      and validation of generic questionnaires was followed, including translation,
      back-translation, pilot testing and clinical validation of the final tool. The
      confirmatory factor analysis was used for clinical validation and the Cronbach's
      alpha coefficient was used to assess the overall internal consistency of the
      final tool. RESULTS: A total of 150 patients with a mean age of 17.0 years
      (SD=2.2 years, range 14-21 years) were enrolled for the final tool validation. Of
      those, 71 patients had juvenile systemic lupus erythematosus (47.3%), 64 had
      juvenile idiopathic arthritis (42.7%), and 15 had juvenile dermatomyositis (10%).
      During the confirmatory factor analysis, the dimension "Talking with providers"
      consisting of two questions, was considered as not fitting the translated
      questionnaire due to a very high ceiling effect and was therefore excluded. All
      other translated items favorably contributed to the overall consistency of the
      final tool; removing that dimension did not result in a substantial increase in
      Cronbach's alpha, which was 0.776. CONCLUSIONS: The Brazilian Portuguese version
      of the Transition Readiness Assessment Questionnaire was validated in a
      population of transitional patients with chronic rheumatologic disorders, after
      one dimension from the original questionnaire was excluded. It is a non-specific
      disease questionnaire; thus, it can be used to evaluate the transition readiness
      of Brazilian patients with other chronic diseases.

PMID- 29457996
TI  - The TyG index cutoff point and its association with body adiposity and lifestyle
      in children.
AB  - OBJECTIVE: To investigate the factors associated with insulin resistance in
      children aged 4-7 years, and to identify the cutoff point of the triglyceride
      glucose index for the prediction of insulin resistance in this population.
      METHODS: A cross-sectional study was conducted with 403 children from a
      retrospective cohort. Insulin resistance was also evaluated in a sub-sample using
      the HOMA index. Four indicators of body adiposity were assessed: body mass index,
      waist-to-height ratio, and the percentages of total and central body fat. Food
      habits were evaluated by the identification of dietary patterns, using principal
      component analysis. Information was also collected on lifestyle, socioeconomic
      status, and breastfeeding time. RESULTS: The median index observed in the sample
      was 7.77, which did not differ between the genders. The shorter the time spent in
      active activities, the higher the triglyceride-glucose value; and increase in the
      values of body adiposity indicators was positively associated with triglyceride
      glucose. The cutoff point with the best balance between sensitivity and
      specificity values was 7.88 (AUC=0.63, 95% CI: 0.51-0.74). CONCLUSION: The
      present study identified that total and central body adiposity and shorter time
      spent in lively activities was positively associated with insulin resistance,
      evaluated through the triglyceride-glucose index. The cutoff point of 7.88 may be
      used in this population for insulin resistance risk screening, but caution is
      required when using it in other populations.

PMID- 29457997
TI  - Detection of Acute and Long-Term Effects of Concussion: Dual-Task Gait Balance
      Control Versus Computerized Neurocognitive Test.
AB  - OBJECTIVE: To examine the acute (within 72h of injury) and long-term (2mo
      postinjury) independent associations between objective dual-task gait balance and
      neurocognitive measurements among adolescents and young adults with a concussion
      and matched controls. DESIGN: Longitudinal case-control. SETTING: Motion analysis
      laboratory. PARTICIPANTS: A total of 95 participants completed the study: 51 who
      sustained a concussion (mean age, 17.5+/-3.3y; 71% men) and 44 controls (mean
      age, 17.7+/-2.9y; 72% men). Participants who sustained a concussion underwent a
      dual-task gait analysis and computerized neurocognitive testing within 72 hours
      of injury and again 2 months later. Uninjured controls also completed the same
      test protocol in similar time increments. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: We compared dual-task gait balance control and computerized
      neurocognitive test performance between groups using independent samples t tests.
      Multivariable binary logistic regression models were then constructed for each
      testing time to determine the association between group membership (concussion vs
      control), dual-task gait balance control, and neurocognitive function. RESULTS:
      Medial-lateral center-of-mass displacement during dual-task gait was
      independently associated with group membership at the initial test (adjusted odds
      ratio [aOR], 2.432; 95% confidence interval [CI], 1.269-4.661) and 2-month follow
      up test (aOR, 1.817; 95% CI, 1.014-3.256) tests. Visual memory composite scores
      were significantly associated with group membership at the initial hour
      postinjury time point (aOR, .953; 95% CI, .833-.998). However, the combination of
      computerized neurocognitive test variables did not predict dual-task gait balance
      control for participants with concussion, and no single neurocognitive variable
      was associated with dual-task gait balance control at either testing time.
      CONCLUSIONS: Dual-task assessments concurrently evaluating gait and cognitive
      performance may allow for the detection of persistent deficits beyond those
      detected by computerized neurocognitive deficits alone.

PMID- 29457998
TI  - Home-based Neuromuscular Electrical Stimulation as an Add-on to Pulmonary
      Rehabilitation Does Not Provide Further Benefits in Patients With Chronic
      Obstructive Pulmonary Disease: A Multicenter Randomized Trial.
AB  - OBJECTIVE: To assess the additional effect of a home-based neuromuscular
      electrical stimulation (NMES) program as an add-on to pulmonary rehabilitation
      (PR), on functional capacity in subjects with chronic obstructive pulmonary
      disease (COPD). DESIGN: Single-blind, multicenter randomized trial. SETTING:
      Three PR centers. PARTICIPANTS: Subjects with severe to very severe COPD (N=73;
      median forced expiratory volume in 1 second, 1L (25th-75th percentile, 0.8-1.4L)
      referred for PR. Twenty-two subjects discontinued the study, but only 1 dropout
      was related to the intervention (leg discomfort). INTERVENTION: Subjects were
      randomly assigned to either PR plus quadricipital home-based NMES (35Hz, 30min, 5
      time per week) or PR without NMES for 8 weeks. MAIN OUTCOME MEASURE: The 6-minute
      walk test (6MWT) was used to assess functional capacity. RESULTS: Eighty-two
      percent of the scheduled NMES sessions were performed. In the whole sample, there
      were significant increases in the distance walked during the 6MWT (P<.01), peak
      oxygen consumption (P=.02), maximal workload (P<.01), modified Medical Research
      Council dyspnea scale (P<.01), and Saint George's Respiratory Questionnaire total
      score (P=.01). There was no significant difference in the magnitude of change for
      any outcome between groups. CONCLUSIONS: Home-based NMES as an add-on to PR did
      not result in further improvements in subjects with severe to very severe COPD;
      moreover, it may have been a burden for some patients.

PMID- 29457999
TI  - Corrigendum to "Molecular adaptive convergence in the alpha-globin gene in
      subterranean octodontid rodents" [Gene, 628 (2017) 275-280].

PMID- 29458001
TI  - Bending the Curve: The Importance of Expertise.

PMID- 29458000
TI  - Evidence for a mitochondrial ATP-regulated potassium channel in human dermal
      fibroblasts.
AB  - Mitochondrial ATP-regulated potassium channels are present in the inner membrane
      of the mitochondria of various cells. In the present study, we show for the first
      time mitochondrial ATP-regulated potassium channels in human dermal fibroblast
      cells. Using the patch-clamp technique on the inner mitochondrial membrane of
      fibroblasts, we detected a potassium channel with a mean conductance equal to 100
      pS in symmetric 150 mM KCl. The activity of this channel was inhibited by a
      complex of ATP/Mg2+ and activated by potassium channel openers such as diazoxide
      or BMS 191095. Channel activity was inhibited by antidiabetic sulfonylurea
      glibenclamide and 5-hydroxydecanoic acid. The influence of substances modulating
      ATP-regulated potassium channel activity on oxygen consumption and membrane
      potential of isolated fibroblast mitochondria was also studied. Additionally, the
      potassium channel opener diazoxide lowered the amount of superoxide formed in
      isolated fibroblast mitochondria. Using reverse transcriptase-PCR, we found an
      mRNA transcript for the KCNJ1(ROMK) channel. The presence of ROMK protein was
      observed in the inner mitochondrial membrane fraction. Moreover, colocalization
      of the ROMK protein and a mitochondrial marker in the mitochondria of fibroblast
      cells was shown by immunofluorescence. In summary, the ATP-regulated
      mitochondrial potassium channel in a dermal fibroblast cell line have been
      identified.

PMID- 29458002
TI  - The effect of time of day testing and utility of 30 and 60 minute cortisol values
      in the 250 mcg ACTH stimulation test.
AB  - BACKGROUND: Despite widespread use of the 250-mcg Cosyntropin test (ACTH test)
      for the diagnosis of adrenal insufficiency (AI), the effect of time of day and
      the utility of performing both 30- and 60-min serum cortisol values remains
      unclear. METHODS: We conducted a retrospective cohort study of all ACTH testing
      at the Halifax Neuropituitary Program, Nova Scotia, Canada between January 2006
      and April 2016. Data were collected on age, gender, medication history, serum
      cortisol levels at 0, 30 and 60 min after ACTH administration, as well as time of
      and indication for testing. RESULTS: There were 336 tests performed, divided by
      time of day (0800-1000 h, 1001-1200 h, and after 1200 h). There were no
      differences in mean cortisol levels at 30 (574.5, 559, 534 nmol/L, respectively;
      p = 0.25) and 60 min (642, 623, 619 nmol/L, respectively; p = 0.63) between
      groups. When comparing 30- vs. 60-min values using a cut-off of >=500 nmol/L, 45
      patients (13.4%) failed to reach the cut-off at 30 min but met the cut-off at 60
      min. Conversely, only 2 patients (0.6%) who met the cut-off at 30 min failed to
      reach it at 60 min. CONCLUSION: We found that outcomes from ACTH testing are not
      affected by time of day. Furthermore, using a 30-min cortisol level in isolation
      results in more than one in seven patients having a false positive diagnosis of
      AI; a 60-min value of >=500 nmol/L alone may be sufficient to diagnose AI in >99%
      of cases.

PMID- 29458003
TI  - FGF 23, PTH and vitamin D status in end stage renal disease patients affected by
      VDR FokI and BsmI variants.
AB  - OBJECTIVES: The aim of this study was to evaluate the association between two VDR
      SNPs FokI and BsmI and mineral status in ESRD patients. DESIGN AND METHODS: Our
      case-control study included 100 patients with chronic renal failure in ESRD and
      149 healthy subjects. We measured the serum Vitamin D levels and the serum intact
      PTH level by Electrochemiluminescence Technology (cobas E411 analyzer). We
      evaluated the serum FGF23 levels by indirect ELISA method. The genotyping of two
      VDR gene variants FokI and BsmI was carried out by PCR-RFLP technique. RESULTS:
      In our study, the FokI TT genotype was associated with lower risk of ESRD
      development (OR = 0.176, Padj = 0.039). The difference in PTH and FGF23 levels
      between cases and controls was statistically significant. The expression of FokI
      CT genotype in subjects with diabetic nephropathy was associated with a negative
      correlation between VD and PTH levels (r = -0.620, P = 0.032) and a positive
      correlation between VD and FGF23 levels (r = 0.967, P = 0.012). A significant
      differences in VD levels between patients and controls was observed in the
      presence of FokI TT (P = 0.044) and CT (P = 0.036) genotypes. The expression of
      FGF23 serum level was significantly elevated in patients than in controls in the
      presence of the FokI CC and BsmI AG genotypes. CONCLUSIONS: In conclusion, our
      study shows the existence of an association between VDR FokI, BsmI polymorphisms
      and mineral status in ESRD patients. The presence of VDR variants affect the
      protein expression of VD, phosphorus, FGF23 and PTH.

PMID- 29458004
TI  - Real-time analysis of cleavage and religation activity of human topoisomerase 1
      based on ternary fluorescence resonance energy transfer DNA substrate.
AB  - Human topoisomerase 1B is a ubiquitous and essential enzyme involved in relaxing
      the topological state of supercoiled DNA to allow the progression of fundamental
      DNA metabolism. Its enzymatic catalytic cycle consists of cleavage and religation
      reaction. A ternary fluorescence resonance energy transfer biosensor based on a
      suicide DNA substrate conjugated with three fluorophores has been developed to
      monitor both cleavage and religation Topoisomerase I catalytic function. The
      presence of fluorophores does not alter the specificity of the enzyme catalysis
      on the DNA substrate. The enzyme-mediated reaction can be tracked in real-time by
      simple fluorescence measurement, avoiding the use of risky radioactive substrate
      labeling and time-consuming denaturing gel electrophoresis. The method is applied
      to monitor the perturbation brought by single mutation on the cleavage or
      religation reaction and to screen the effect of the camptothecin anticancer drug
      monitoring the energy transfer decrease during religation reaction. Pathological
      mutations usually affect only the cleavage or the religation reaction and the
      proposed approach represent a fast protocol for assessing chemotherapeutic drug
      efficacy and analyzing mutant's properties.

PMID- 29458005
TI  - 14-3-3zeta promotes esophageal squamous cell carcinoma invasion by repressing
      S1PR2 protein expression through NF-kappaB signaling.
AB  - 14-3-3zeta is overexpressed in several cancers, including esophageal squamous
      cell carcinoma (ESCC), and plays an important role in tumorigenesis. However, the
      mechanisms underlying its tumorigenesis remain unclear. Here we report that 14-3
      3zeta was upregulated in ESCC tumors, compared with adjacent normal tissues; 14-3
      3zeta levels were positively correlated with ESCC lymph node metastasis and
      recurrence. Overexpression of 14-3-3zeta promoted the tumor growth and invasion
      of ESCC in vitro and in vivo, whereas depletion of 14-3-3zeta suppressed these
      effects. Moreover, 14-3-3zeta reduces expression of genes mediating S1P/S1PR2
      signaling, and this effect is mediated through activation of NF- kappa B. Taken
      together, 14-3-3zeta contributes to ESCC tumorigenesis and progression through
      repressing S1PR2 signaling and may act as a new therapeutic target for ESCC.

PMID- 29458006
TI  - Mechanistic studies of formate oxidase from Aspergillus oryzae: A novel member of
      the glucose-Methanol-choline oxidoreductase enzyme superfamily that oxidizes
      carbon acids.
AB  - Formate oxidase (FOX) from Aspergillus oryzae is the only GMC member that
      oxidizes a carbon acid rather than alcohols; thus, its catalytic mechanism may be
      different from that of other GMC members. We have used pH, solvent viscosity, and
      deuterium kinetic isotope effects, to investigate the catalytic mechanism of FOX.
      The enzyme followed a Bi-Bi sequential steady-state kinetic mechanism. The kcat
      value was pH-independent between pH 2.8 and 6.8, suggesting a lack of ionizable
      groups in kinetic step(s) that limit the overall turnover of the enzyme. The
      kcat/Kformate value decreased from a value of 10,000 M-1s-1 at low pH with a pKa
      value of 4.4, consistent with the requirement of a protonated group for substrate
      binding. An inverse viscosity dependence on the kcat/Kformate value indicated an
      isomerization of the Michaelis complex. The kcat/Koxygen value was 340,000 M-1s-1
      and pH independent up to pH 6.0. The Dkcat and D(kcat/Kformate) values were 2.5
      and 1.9, respectively, indicating that substrate CH bond cleavage is rate
      limiting for FOX catalysis. Analytical ultracentrifugation indicated a
      concentration dependence of the oligomeric state of FOX. The appkred,H value was
      ~75% that of kcat,H, indicating that the anaerobic reduction of FOX was dependent
      on the oligomeric state of FOX.

PMID- 29458007
TI  - A Genomically Characterized Collection of High-Grade Serous Ovarian Cancer
      Xenografts for Preclinical Testing.
AB  - High-grade serous ovarian cancer (HGSC) is the leading cause of morbidity and
      mortality from gynecologic malignant tumors. Overall survival remains low because
      of the nearly ubiquitous emergence of platinum resistance and the paucity of
      effective next-line treatments. Current cell culture-based models show limited
      similarity to HGSC and are therefore unreliable predictive models for preclinical
      evaluation of investigational drugs. This deficiency could help explain the low
      overall rate of successful drug development and the decades of largely unchanged
      approaches to HGSC treatment. We used gene expression, copy number variation, and
      exome sequencing analyses to credential HGSC patient-derived xenografts (PDXs) as
      effective preclinical models that recapitulate the features of human HGSC. Mice
      bearing PDXs were also treated with standard-of-care carboplatin therapy. PDXs
      showed similar sensitivity to carboplatin as the patient's tumor at the time of
      sampling. PDXs also recapitulated the diversity of genomic alterations (copy
      number variation and mutation profiles) previously described in large data sets
      that profiled HGSC. Furthermore, mRNA profiling showed that the PDXs represent
      all HGSC subtypes with the exception of the immunoreactive group. Credentialing
      of PDX models of HGSC should aid progress in HGSC research by providing improved
      preclinical models of HGSC that can be used to test novel targets and more
      accurately evaluate their likelihood of success.

PMID- 29458009
TI  - The Four-and-a-Half LIM Domain Protein 2 Supports Influenza A Virus-Induced Lung
      Inflammation by Restricting the Host Adaptive Immune Response.
AB  - Four-and-a-half LIM domain protein 2 (FHL2) is a multifunctional adaptor protein
      with fine-tuning adjustment properties. It acts as a regulator of signaling
      cascades but also as a cofactor of transcription and controls several anti
      inflammatory immune responses. Recently, we described FHL2 as a novel regulator
      of influenza A virus propagation. We have shown that in vitro FHL2 restricts
      viral replication by accelerating the interferon regulatory factor 3-dependent
      transcription of the Ifnb1 gene. In this work, we unraveled an ambiguous role of
      FHL2 during influenza A virus infection in vivo. Although FHL2 restrained viral
      replication during the first 24 hours of infection, it significantly delayed
      viral clearance afterward. Comparison of lung immune status of wild-type and FHL2
      knockout mice during influenza virus infection did not acknowledge significant
      differences in the innate host immune response but revealed an improved migration
      of dendritic cells from infected lungs into draining lymph nodes as well as
      increased levels of activated CD8+ T lymphocytes accumulated in the lungs of FHL2
      knockout mice.

PMID- 29458008
TI  - Trefoil Factor 2 Promotes Type 2 Immunity and Lung Repair through Intrinsic Roles
      in Hematopoietic and Nonhematopoietic Cells.
AB  - Trefoil factors (TFFs) are small secreted proteins that regulate tissue integrity
      and repair at mucosal surfaces, particularly in the gastrointestinal tract.
      However, their relative contribution(s) to controlling baseline lung function or
      the extent of infection-induced lung injury are unknown issues. With the use of
      irradiation bone marrow chimeras, we found that TFF2 produced from both
      hematopoietic- and nonhematopoietic-derived cells is essential for host
      protection, proliferation of alveolar type 2 cells, and restoration of pulmonary
      gas exchange after infection with the hookworm parasite Nippostrongylus
      brasiliensis. In the absence of TFF2, lung epithelia were unable to proliferate
      and expressed reduced lung mRNA transcript levels for type 2 response-inducing IL
      25 and IL-33 after infectious injury. Strikingly, even in the absence of
      infection or irradiation, TFF2 deficiency compromised lung structure and
      function, as characterized by distended alveoli and reduced blood oxygen levels
      relative to wild-type control mice. Taken together, we show a previously
      unappreciated role for TFF2, produced by either hematopoietic or nonhematopoietic
      sources, as a pro-proliferative factor for lung epithelial cells under steady
      state and infectious injury conditions.

PMID- 29458010
TI  - Galectin-9 Is Critical for Mucosal Adaptive Immunity through the T Helper 17-IgA
      Axis.
AB  - Impairment of the intestinal mucosal immunity significantly increases the risk of
      acute and chronic diseases. IgA plays a major role in humoral mucosal immunity to
      provide protection against pathogens and toxins in the gut. Here, we investigated
      the role of endogenous galectin-9, a tandem repeat-type beta-galactoside-binding
      protein, in intestinal mucosal immunity. By mucosal immunization of Lgals9-/- and
      littermate control mice, it was found that lack of galectin-9 impaired mucosal
      antigen-specific IgA response in the gut. Moreover, Lgals9-/- mice were more
      susceptible to developing watery diarrhea and more prone to death in response to
      high-dose cholera toxin. The results indicate the importance of galectin-9 in
      modulating intestinal adaptive immunity. Furthermore, bone marrow chimera mice
      were established, and galectin-9 in hematopoietic cells was found to be critical
      for adaptive IgA response. In addition, immunized Lgals9-/- mice exhibited lower
      expression of Il17 and fewer T helper 17 (Th17) cells in the lamina propria,
      implying that the Th17-IgA axis is involved in this mechanism. Taken together,
      these findings suggest that galectin-9 plays a role in mucosal adaptive immunity
      through the Th17-IgA axis. By manipulating the expression or activity of galectin
      9, intestinal mucosal immune response can be altered and may benefit the
      development of mucosal vaccination.

PMID- 29458011
TI  - Inflammatory Cytokines Induce Podoplanin Expression at the Tumor Invasive Front.
AB  - Tumor invasion is a critical first step in the organismic dissemination of cancer
      cells and the formation of metastasis in distant organs, the most important
      prognostic factor and the actual cause of death in most of the cancer patients.
      We report herein that the cell surface protein podoplanin (PDPN), a potent
      inducer of cancer cell invasion, is conspicuously expressed by the invasive front
      of squamous cell carcinomas (SCCs) of the cervix in patients and in the
      transgenic human papillomavirus/estrogen mouse model of cervical cancer. Laser
      capture microscopy combined with gene expression profiling reveals that the
      expression of interferon-responsive genes is up-regulated in PDPN-expressing
      cells at the tumor invasive front, which are exposed to CD45-positive
      inflammatory cells. Indeed, PDPN expression can be induced in cultured SCC cell
      lines by single or combined treatments with interferon-gamma, transforming growth
      factor-beta, and/or tumor necrosis factor-alpha. Notably, shRNA-mediated ablation
      of either PDPN or STAT1 in A431 SCC cells repressed cancer cell invasion on s.c.
      transplantation into immunodeficient mice. The results highlight the induction of
      tumor cell invasion by the inflammatory cytokine-stimulated expression of PDPN in
      the outermost cell layers of cervical SCC.

PMID- 29458012
TI  - KLF10 Gene Expression Modulates Fibrosis in Dystrophic Skeletal Muscle.
AB  - Dystrophic skeletal muscle is characterized by fibrotic accumulation of
      extracellular matrix components that compromise muscle structure, function, and
      capacity for regeneration. Tissue fibrosis is often initiated and sustained
      through transforming growth factor-beta (TGF-beta) signaling, and Kruppel-like
      factor 10 (KLF10) is an immediate early gene that is transcriptionally activated
      in response to TGF-beta signaling. It encodes a transcriptional regulator that
      mediates the effects of TGF-beta signaling in a variety of cell types. This
      report presents results of investigation of the effects of loss of KLF10 gene
      expression in wild-type and dystrophic (mdx) skeletal muscle. On the basis of RT
      PCR, Western blot, and histological analyses of mouse tibialis anterior and
      diaphragm muscles, collagen type I (Col1a1) and fibronectin gene expression and
      protein deposition were increased in KLF10-/- mice, contributing to increased
      fibrosis. KLF10-/- mice displayed increased expression of genes encoding SMAD2,
      SMAD3, and SMAD7, particularly in diaphragm muscle. SMAD4 gene expression was
      unchanged. Expression of the extracellular matrix remodeling genes, MMP2 and
      TIMP1, was also increased in KLF10-deficient mouse muscle. Histological analyses
      and assays of hydroxyproline content indicated that the loss of KLF10 increased
      fibrosis. Dystrophic KLF10-null mice also had reduced grip strength. The effects
      of loss of KLF10 gene expression were most pronounced in dystrophic diaphragm
      muscle, suggesting that KLF10 moderates the fibrotic effects of TGF-beta
      signaling in chronically damaged regenerating muscle.

PMID- 29458013
TI  - Argonaute 2 RNA Immunoprecipitation Reveals Distinct miRNA Targetomes of Primary
      Burkitt Lymphoma Tumors and Normal B Cells.
AB  - miRNAs are small noncoding RNAs involved in the posttranscriptional regulation of
      gene expression. Deregulated miRNA levels have been linked to Burkitt lymphoma
      (BL) pathogenesis. To date, the number of known pathogenesis-related miRNA-target
      gene interactions is limited. Here, we determined for the first time the miRNA
      targetomes of primary BL tumors and normal B cells. AGO2-RNA immunoprecipitation
      of two frozen diagnostic BL tissue samples and three CD19+ B-cell samples
      isolated from routinely removed tonsils showed distinct miRNA targetomes of BL
      and normal B cells. In contrast to normal B cells, miRNA target genes in BL were
      enriched for targets of the oncogenic miR-17 to 92 cluster, and were involved
      mainly in cell cycle and cell death. Immunohistochemistry on BL and tonsil
      tissues confirmed altered protein levels for two of six selected miRNA targets,
      in line with the differential AGO2-IP enrichment between BL and normal B cells. A
      comparison of AGO2-IP-enriched genes in primary BL cases with BL cell lines
      indicated that despite a considerable overlap, the miRNA targetomes of BL cell
      lines show substantial differences with the targetomes of primary BL tumors. In
      summary, we identified distinct miRNA targetomes of BL and normal B cells, and
      showed both the necessity and feasibility of studying miRNA-target gene
      interactions in primary tumors.

PMID- 29458015
TI  - Sulfenamide and sulfonamide derivatives of metformin can exert anticoagulant and
      profibrinolytic properties.
AB  - Type 2 diabetes mellitus (T2DM) is characterised not only by hyperglycaemia and
      insulin resistance but also an impaired balance between the processes of
      coagulation and fibrinolysis. The aim of this study was to examine the effects of
      metformin, a widely-used oral anti-diabetic drug, phenformin and eight
      sulfenamide and sulfonamide derivatives of metformin on several haemostasis
      parameters. Thrombin Time (TT) tests were performed according to the available
      commercial method. The activity of factor X was conducted based on deficient
      plasma factor X. The activity of two main enzymes involved in haemostasis,
      thrombin and plasmin, was measured spectrophotometrically with chromogenic
      substrates. Protein C and antithrombin III (AT) activity assays using chromogenic
      substrates were conducted to determine the effect of the derivatives of metformin
      on these both naturally occurring anticoagulants. Two of the compounds,
      sulfenamide with hexyl tail and para-nitro-benzenesulfonamide significantly
      shortened TT. ortho-nitro sulfonamide at a concentration of 0.3-1.5 MUmol/mL
      contributed to a significant decrease in the activity of factor X. However,
      sulfenamides with cyclohexyl, butyl and branched ethyl-hexyl tails at 1.5 of
      MUmol/mL increased its activity, and simultaneously shortened PT. Additionally,
      ortho-nitro-benzenesulfonamide at concentrations of 1.5 MUmol/mL was found to
      significantly decrease reaction velocity (? dA/dt) in the thrombin activity
      assay. On contrary, it was noticed that branched sulfenamide at the concentration
      of 1.5 MUmol/mL significantly increased the enzymatic activity of plasmin.
      Metformin, phenformin and octyl and butyl sulfenamides were associated with a
      significant increase in the activity of AT. Hexyl sulfenamide and para-nitro- as
      well as para-trifluoro-ortho-nitro-benzenesulfonamide contributed to the decrease
      in the activity of protein C, while the other tested compounds did not affect its
      activity. In conclusion, 2-nitro-benzenesulfonamide derivative of metformin
      presents highly beneficial anticoagulant properties. This compound is therefore
      promising candidate for further in vitro and in vivo studies.

PMID- 29458014
TI  - Topical delivery of l-theanine ameliorates TPA-induced acute skin inflammation
      via downregulating endothelial PECAM-1 and neutrophil infiltration and
      activation.
AB  - l-theanine, the most abundant free amino acid in tea, has been documented to
      possess many different bioactive properties through oral or intragastrical
      delivery. However, little is known about the effect of topical delivery of l
      theanine on acute inflammation. In the present study, by using 12-O
      tetradecanoylphorbol-13-acetate (TPA, 2.5 MUg/ear)-induced ear edema model in
      mice, we first found that single-dose local pretreatment of l-theanine 30 min
      before TPA time- and dose-dependently suppressed the increases in both skin
      thickness and weight. Subsequently l-theanine ameliorated TPA-induced erythema,
      vascular permeability increase, epidermal and dermal hyperplasia, neutrophil
      infiltration and activation via downregulating the expression of PECAM-1 (a
      platelet endothelial adhesion molecule-1) in blood vessels and the production of
      pro-inflammatory cytokines IL-1beta, TNF-alpha, and mediator cyclooxygenase-2
      (COX-2), which is mainly expressed in neutrophils. It highlighted the potential
      of l-theanine as a locally administrable therapeutic agent for acute cutaneous
      inflammation.

PMID- 29458016
TI  - Renal toxicological evaluations of sulphonated nanocellulose from Khaya
      sengalensis seed in Wistar rats.
AB  - Nanocellulose is currently gaining attention due to its unique properties. This
      attention includes its application as building blocks for developing novel
      functional materials, plant drug and also in drug delivery systems. However, its
      safety remains largely untested or less understood. Thus, sulphonated
      nanocellulose (KSS) was prepared from cellulose (KSC) isolated from Khaya
      senegalensis seed (KS). KS, KSC and KSS were characterized using Fourier
      transformed infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis
      (TG), particle size distribution (PSD), zeta potential and scanning electron
      microscopy (SEM). The impact of KSS on selected renal markers of oxidative
      stress, inflammation and apoptosis in Wistar rats was also investigated. Thus,
      male rats were randomly assigned to four groups of five animals each and were
      treated with KSS (0, 50, 75 and 100 mg/kg BW) for 14 days. Thereafter, biomarkers
      of renal oxidative damage, inflammation and immunohistochemical expressions of
      iNOS, COX-2, Bcl-2 and p53 were evaluated. The results revealed KSS to have
      crystallinity of 70.40%, it was monomodal and has a flaky surface with
      agglomerations. KSS had no effect on markers of kidney function and oxidative
      damage, although there was a generalized hypernatremia after 14 days of exposure.
      Lastly, KSS enhanced the antioxidant status and immunohistochemical expressions
      of iNOS and COX-2 in the kidney of the rats. While the biomedical applications of
      KSS may appear plausible, our data suggests that it could induce renal toxicity
      via the combined impacts of electrolyte imbalance and inflammation.

PMID- 29458017
TI  - Synergistic and additive effects of ATRA in combination with different anti-tumor
      compounds.
AB  - All-trans retinoic acid (ATRA), a derivative of vitamin A, has been shown to
      potentiate cancer chemotherapy due to its ability to induce signals for cell
      differentiation or death, and inhibit cell proliferation. The combination of ATRA
      with taxoids, kinase inhibitors, natural compounds, retinoids, ER or HER2
      inhibitors, chemotherapeutic drugs, proteasome inhibitors and nanoformulations of
      tretinoin have demonstrated additive or synergistic effects in anti-cancer
      activities. The mechanisms by which the compounds exert their synergistic effects
      depend on the tumor and the cell type. However, several experiments demonstrated
      similar mechanisms such as reduction of PCK, c-myc, E2F and Bcl-2, as well as
      increase of p21 and TGF-beta. When the apoptotic synergistic effect was observed,
      the predominant effect of ATRA was in differentiation induction. The results
      indicate that future combinations of ATRA and anti-tumor agents hold promise to
      enhance and improve anti-carcinogenic therapies.

PMID- 29458018
TI  - 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-((4-methylpiperazin
      1-yl)methyl)-1H-1,2,3-triazol-1-yl)phenyl)pyrimidine-2,4-diamine (WY-135), a
      novel ALK inhibitor, induces cell cycle arrest and apoptosis through inhibiting
      ALK and its downstream pathways in Karpas299 and H2228 cells.
AB  - Anaplastic lymphoma kinase (ALK)-positive cancers have rising morbidity and
      mortality in recent years, and novel chemotherapeutic drugs with no drug
      resistance and high activity for treating ALK-positive cancers are needed
      urgently. In this study, we investigated the anti-cancer effect of 5-chloro-N4-(2
      (isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-((4-methylpiperazin-1-yl)methyl)-1H
      1,2,3-triazol-1-yl)phenyl)pyrimidine-2,4-diamine (WY-135), a novel ALK inhibitor,
      on nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) positive cancer cell line
      Karpas299 and echinoderm microtubule associated protein like 4-anaplastic
      lymphoma kinase (EML4-ALK) positive cancer cell line H2228. In vitro enzyme assay
      showed that WY-135 had better enzyme inhibitory activity than ceritinib. MTT
      assay showed that WY-135 had similar inhibitory activity with ceritinib in
      Karpas299 and H2228 cells. The cell cycle analysis proved that WY-135 induced
      cell cycle arrest at G1 phase in a dose-dependent manner and subsequently
      progressed into apoptosis. Real-time PCR analysis revealed that the mRNA level of
      ALK was significantly reduced in Karpas299 and H2228 cells treatment with WY-135.
      Furthermore, western blot analysis showed that WY-135 significantly suppressed
      ALK and its downstream protein expression. Taken together, WY-135 exhibits
      significant anti-cancer activity through inhibiting ALK and its downstream
      protein expression, arresting cell cycle and eventually inducing cell apoptosis
      in Karpas299 and H2228 cells. WY-135 is a promising ALK inhibitor with novel
      structure that has tremendous potentials for therapeutic treatment of NPM-ALK or
      EML4-ALK positive cancers.

PMID- 29458019
TI  - Raffinose from Costus speciosus attenuates lipid synthesis through modulation of
      PPARs/SREBP1c and improves insulin sensitivity through PI3K/AKT.
AB  - Among several metabolic disorders, the pathogenesis of insulin resistance is
      considered to be multifactorial. Raffinose, an oligosaccharide isolated from the
      rhizome of Costus speciosus showed <=50% inhibition of lipid accumulation in
      differentiated HepG2 and 3T3-L1 cells through exhibiting partial agonism to
      PPARgamma, and, an enhanced secretion of adiponectin in 3T3-L1 adipocytes.
      Raffinose was also observed to attenuate the expression of SREBP1c, ACC and FAS
      which are involved in the fatty acid synthesis. A corresponding upregulation of
      PPARalpha and ACO involved in fatty acid oxidation was observed in steatotic
      HepG2 hepatocytes and 3T3-L1 adipocytes. In vitro evaluation of its anti-diabetic
      potential showed a dose dependent enhancement of glucose uptake. Investigation of
      the insulin sensitizing efficacy of Raffinose revealed an increase in Glut4
      translocation via phosphorylation of IRbeta/PI3K/Akt in differentiated L6
      myocytes and 3T3-L1 preadipocytes. In addition, Raffinose was potentially
      involved in glycogen synthesis by inhibiting the activation of GSK3beta. Hence,
      Raffinose could be a useful therapeutic agent for metabolic maladies.

PMID- 29458020
TI  - CircRNA circ_0067934 promotes tumor growth and metastasis in hepatocellular
      carcinoma through regulation of miR-1324/FZD5/Wnt/beta-catenin axis.
AB  - Recently, increasing evidences demonstrate that circular RNAs (circRNAs) exert
      very important functions in the progression of human cancers. However, the
      functions and molecular mechanism of circ_0067934 in hepatocellular carcinoma
      (HCC) are largely unknown. In the present study, we found that the expression of
      circ_0067934 was significantly upregulated in HCC tissues and cell lines compared
      to adjacent normal tissues. Furthermore, we showed that circ_0067934 knockdown
      remarkably suppressed the proliferation, migration and invasion of Hep3B and HuH7
      cells while inducing their apoptosis. In terms of mechanism, we found that
      circ_0067934 directly suppressed miR-1324, which targeted the 3'-UTR of FZD5 mRNA
      and subsequently downregulated the Wnt/beta-catenin signaling pathway in HCC.
      Through rescue experiments, we demonstrated that circ_0067934 enhanced the
      proliferation, migration and invasion of HCC cells by the inhibition of miR-1324
      and concomitant activation of FZD5/Wnt/beta-catenin signaling pathway. In
      summary, the circ_0067934/miR-1324/FZD5/beta-catenin signaling axis might serve
      as a promising therapeutic target for HCC intervention.

PMID- 29458021
TI  - Increased mortality from influenza infection in long-chain acyl-CoA dehydrogenase
      knockout mice.
AB  - We previously showed that the mitochondrial fatty acid oxidation enzyme long
      chain acyl-CoA dehydrogenase (LCAD) is expressed in alveolar type II pneumocytes
      and that LCAD-/- mice have altered breathing mechanics and surfactant defects.
      Here, we hypothesized that LCAD-/- mice would be susceptible to influenza
      infection. Indeed, LCAD-/- mice demonstrated increased mortality following
      infection with 2009 pandemic influenza (A/CA/07/09). However, the mortality was
      not due to increased lung injury, as inflammatory cell counts, viral titers, and
      histology scores all showed non-significant trends toward milder injury in LCAD-/
      mice. To confirm this, LCAD-/- were infected with a second, mouse-adapted H1N1
      virus (A/PR/8/34), to which they responded with significantly less lung injury.
      While both strains become increasingly hypoglycemic over the first week post
      infection, LCAD-/- mice lose body weight more rapidly than wild-type mice.
      Surprisingly, while acutely fasted LCAD-/- mice develop hepatic steatosis,
      influenza-infected LCAD-/- mice do not. They do, however, become more hypothermic
      than wild-type mice and demonstrate increased blood lactate values. We conclude
      that LCAD-/- mice succumb to influenza from bioenergetic starvation, likely due
      to increased reliance upon glucose for energy.

PMID- 29458022
TI  - Generation of anti-oligosaccharide antibodies that recognize mammalian
      glycoproteins by immunization with a novel artificial glycosphingolipid.
AB  - Here we report a new method for the efficient generation of antibodies that
      recognize the fine structures of oligosaccharides on glycoproteins. We found a
      newly designed artificial glycosphingolipid carrying a very long chain fatty acid
      to be a strong immunogen in mice, with the serum of immunized mice containing
      antibodies recognizing the oligosaccharide structure of the immunogen. First, we
      found that conjugation of a simple ceramide analogue to target oligosaccharides
      could enhance the immunogenicity of these oligosaccharides in these immunized
      mice. This effect was confirmed in mice immunized with the artificial
      glycosphingolipids carrying 6'-Sialyl-LacNAc, 3'-Sialyl-LacNAc and LacNAc. Next,
      we tried to improve the immunogenic enhancing effect of the ceramide analogue. In
      a model experiment using 6'-Sialyl-LacNAc oligosaccharide, we manipulated the
      alkyl chains to several lengths, and found that a longer alkyl chain length of
      the fatty acid correlated with high immunogenicity. Among these we examined,
      artificial glycosphingolipids conjugated with a ceramide analogue carrying a very
      long chain fatty acid (lignoceric acid) showed the strongest immunogenicity. By
      using the artificial glycosphingolipid containing 6'-Sialy-LacNAc and lignoceric
      acid, we succeeded in the generation of a new anti-6'-Sialyl-LacNAc antibody that
      recognizes 6'-Sialyl-LacNAc carrying glycoproteins but does not bind to 6'
      Sialyllactose, asialo-glycoporoteins and glycoproteins carrying 3'-Sialyl-LacNAc.
      These results indicate that the established technology is valuable for the
      targeted generation of monoclonal antibodies against glycoproteins containing
      specific oligosaccharide structures.

PMID- 29458023
TI  - Structural characterization of the HCoV-229E fusion core.
AB  - HCoV-229E spike (S) protein mediates virion attachment to cells and subsequent
      fusion of the viral and cellular membranes. This protein is composed of an N
      terminal receptor-binding domain (S1) and a C-terminal trans-membrane fusion
      domain (S2). S2 contains a highly conserved heptad repeat 1 and 2 (HR1 and HR2).
      In this study, the HRs sequences were designed and connected with a flexible
      linker. The recombinant fusion core protein was crystallized and its structure
      was solved at a resolution of 2.45 A. Then we characterized the binding of HR1s
      and HR2s via both sequence alignment and structural analysis. The overall
      structures, especially the residues in some positions of HR2 are highly
      conserved. Fourteen hydrophobic and three polar residues from each HR1 peptide
      are packed in layers at the coiled-coil interface. These core amino acids can be
      grouped into seven heptad repeats. Analysis of hydrophobic and hydrophilic
      interactions between HR2 helix and HR1 helices, shows that the HR1 and HR2
      polypeptides are highly complementary in both shape and chemical properties.
      Furthermore, the available knowledge concerning HCoV-229E fusion core may make it
      possible to design small molecule or polypeptide drugs targeting membrane fusion,
      a crucial step of HCoV-229E infection.

PMID- 29458024
TI  - Spinal cord-specific deletion of the glutamate transporter GLT1 causes motor
      neuron death in mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disorder
      characterized by the selective loss of motor neurons. The precise mechanisms that
      cause the selective death of motor neurons remain unclear, but a growing body of
      evidence suggests that glutamate-mediated excitotoxicity has been considered to
      play an important role in the mechanisms of motor neuron degeneration in ALS.
      Reductions in glutamate transporter GLT1 have been reported in animal models of
      ALS and the motor cortex and spinal cord of ALS patients. However, it remains
      unknown whether the reduction in GLT1 has a primary role in the induction of
      motor neuron degeneration in ALS. Here, we generated conditional knockout mice
      that lacked GLT1 specifically in the spinal cord by crossing floxed-GLT1 mice and
      Hoxb8-Cre mice. Hoxb8-Cre/GLT1flox/flox mice showed motor deficits and motor
      neuron loss. Thus, loss of the glial glutamate transporter GLT1 is sufficient to
      cause motor neuron death in mice.

PMID- 29458025
TI  - Cell model for the identification and characterization of prion-like components
      from Alzheimer brain tissue.
AB  - Intracerebral injection of brain extracts from Alzheimer's disease (AD) patients
      into appropriate mouse models was previously found to drastically accelerate the
      deposition of Abeta amyloid in the recipient animals indicating a prion-like
      activity. In this study we show that this prion-like activity can be also
      identified by using a cell culture model of Abeta plaque formation. Analysis of
      biochemical fractions of AD brain extract indicate that the seeding-activity
      correlated with the presence of Abeta peptide and Abeta-derived aggregates. In
      vitro-formed fibrils were also active but their activity was low and depending on
      the fibril structure and conditions of fibril formation. Our data indicate a
      conformational basis of the observed seeding effect and suggest the utility of
      our cell model for further studies on the prion-like activity of AD extracts.

PMID- 29458026
TI  - Knockdown of fascin-1 expression suppresses cell migration and invasion of non
      small cell lung cancer by regulating the MAPK pathway.
AB  - Fascin-1 is a cytoskeletal protein and it can specifically bind to F-actin, it
      can be abnormally expressed in a variety of solid tumors. Fascin-1 was identified
      as a factor for poor prognosis in non-small cell lung cancer (NSCLC). However,
      the relevant molecular mechanisms are not yet fully understood. In this study,
      the fascin-1 knockdown cells were produced by lentivirus infection, and then cell
      proliferation, invasion and cell migration assay were used to investigate the
      role of fascin-1 in NSCLC cells. The MAPK pathway related proteins were
      determined by western blot. In the current study, lentivirus-mediated fascin-1
      knockdown significantly decreased the proliferation of NSCLC cells. Furthermore,
      fascin-1 silencing partly inhibited cell invasion and migration. Inhibition of
      fascin-1 decreased the activity of the MAPK pathway. Therefore, targeting fascin
      1 may inhibit the growth and metastasis of NSCLC cells, which is a potentially
      effective therapeutic strategy for treating NSCLC.

PMID- 29458027
TI  - Invasive Cutaneous Facial Mucormycosis in a Trauma Patient.
AB  - Mucormycosis, also known as zygomycosis, is an aggressive infection caused by a
      ubiquitous group of molds known as mucormycetes and is often associated with
      immune suppression or trauma among immunocompetent populations. We present the
      case of a 19-year-old woman who was involved in a motor vehicle accident in whom
      rapidly progressive invasive cutaneous facial mucormycosis subsequently
      developed. The diagnosis, treatment options, and incidence of this disease
      process are discussed in the context of trauma.

PMID- 29458028
TI  - Are Portable Stereophotogrammetric Devices Reliable in Facial Imaging? A
      Validation Study of VECTRA H1 Device.
AB  - PURPOSE: Modern 3-dimensional (3D) image acquisition systems represent a crucial
      technologic development in facial anatomy because of their accuracy and
      precision. The recently introduced portable devices can improve facial databases
      by increasing the number of applications. In the present study, the VECTRA H1
      portable stereophotogrammetric device was validated to verify its applicability
      to 3D facial analysis. MATERIALS AND METHODS: Fifty volunteers underwent 4 facial
      scans using portable VECTRA H1 and static VECTRA M3 devices (2 for each
      instrument). Repeatability of linear, angular, surface area, and volume
      measurements was verified within the device and between devices using the Bland
      Altman test and the calculation of absolute and relative technical errors of
      measurement (TEM and rTEM, respectively). In addition, the 2 scans obtained by
      the same device and the 2 scans obtained by different devices were registered and
      superimposed to calculate the root mean square (RMS; point-to-point) distance
      between the 2 surfaces. RESULTS: Most linear, angular, and surface area
      measurements had high repeatability in M3 versus M3, H1 versus H1, and M3 versus
      H1 comparisons (range, 82.2 to 98.7%; TEM range, 0.3 to 2.0 mm, 0.4 degrees  to
      1.8 degrees ; rTEM range, 0.2 to 3.1%). In contrast, volumes and RMS distances
      showed evident differences in M3 versus M3 and H1 versus H1 comparisons and
      reached the maximum when scans from the 2 different devices were compared.
      CONCLUSION: The portable VECTRA H1 device proved reliable for assessing linear
      measurements, angles, and surface areas; conversely, the influence of involuntary
      facial movements on volumes and RMS distances was more important compared with
      the static device.

PMID- 29458029
TI  - Editorial Comment.

PMID- 29458030
TI  - Reply by Authors.

PMID- 29458031
TI  - Reply by Authors.

PMID- 29458032
TI  - Editorial Comment.

PMID- 29458033
TI  - Editorial Comment.

PMID- 29458034
TI  - Fluorescence-linked immunosorbent assay for detection of phenanthrene and its
      homolog.
AB  - A competitive fluorescence-linked immunosorbent assay (FLISA) was developed using
      rhodamine B isothiocyanate (RBITC) as the model fluorescent dye conjugate
      monoclonal antibody (McAb) for detection of Phe and its homolog (acenaphthene,
      fluorene, fluoranthene, pyrene and indeno [1,2,3-cd] pyrene) in water samples.
      The detection range of the assay for Phe was from 2.10 to 91.95 ng/mL. The limit
      of detection was 1.05 ng/mL, which was approximately 2-fold lower than that of
      traditional ic-ELISA. Compared with traditional ic-ELISA, more than 70 min was
      saved because of only one immunoreaction step was needed to accomplish the assay.
      The average recoveries of Phe and its homolog from domestic water, contaminated
      water and natural water were 100.7%, 100.8% and 101.2% respectively. The accuracy
      and precision of the developed FLISA were validated with GC-MS/MS. There were
      good correlation between the two methods from tap water, contaminated water and
      river water samples were 0.9994, 0.9935 and 0.9967, respectively. The results
      suggested that the proposed FLISA could be a potential alternative format for
      rapid, sensitive, and quantitative detection of Phe and its homolog in
      environmental water.

PMID- 29458035
TI  - Lectin-carbohydrate complex evaluation by chemiluminescence.
AB  - In order to characterize the affinity between specific carbohydrate-binding
      proteins such as lectins, a model is proposed to study these interactions using a
      polysaccharide membrane to simulate such adsorption. Here, lectin-carbohydrate
      interactions were chemiluminescently investigated using lectins conjugated to
      acridinium ester (AE) and polysaccharides composed of their respective specific
      carbohydrates. The lectin-AE conjugates were incubated with discs (0.0314-0.6358
      cm2) of phytagel, chitosan and carrageenan. The complex formation
      chemiluminescently detected followed the Langmuir isotherm from which constants
      were estimated. The association constant (Ka) and maximum binding sites on the
      membranes were 2.4 * 10-7 M-1 +/- 0.8 * 10-7 M-1 and 1.3 * 10-3 mol. mg-1 +/- 0.3
      * 10-3 mol. mg-1 (Con A); 0.9 * 10-6 M-1 +/- 0.4 * 10-6 M-1 and 0.021 * 10-3 mol.
      mg-1 +/- 0.003 * 10-3 mol. mg-1 (WGA) and 2.0 * 10-6 M-1 +/- 0.9 * 10-6 M-1 and
      0.069 * 10-3 mol. mg-1 +/- 0.010 * 10-3 mol. mg-1 (PNA). The proposed model might
      be useful to study binding affinity and estimate the amount of binding not
      limited by the sugar content in the membrane.

PMID- 29458037
TI  - Distinguishing Keratoconic Eyes and Healthy Eyes Using Ultrahigh-Resolution
      Optical Coherence Tomography-Based Corneal Epithelium Thickness Mapping.
AB  - PURPOSE: To find differences in epithelial thickness (ET) maps of eyes with
      keratoconus (KC) and healthy eyes. DESIGN: Institutional cross-sectional study.
      METHODS: In this study 40 keratoconic eyes and 76 healthy eyes were scanned using
      a custom-built ultrahigh-resolution optical coherence tomography system.
      Automated segmentation ET maps with 17 subsectors were calculated (central,
      temporal inferior, temporal superior, nasal inferior, and nasal superior area).
      The thinnest point of the epithelium (minET), the thickest point of the
      epithelium (maxET), and the thinnest point diagonally opposing the thickest point
      (ETmax/op) were additional parameters. Ratios were calculated as follows:
      minET/diagonally opposing point (R1), maxET/diagonally opposing point (R2),
      inferior temporal area/superior nasal area (RTI/NS), and inferior/superior
      hemisphere (RI/S). Furthermore, collected parameters were analyzed regarding
      their diagnostic accuracy (area under the curve; AUC). RESULTS: Statistically
      significant differences were as follows: central ET, 46.25 +/- 2.56/50.91 +/-
      1.66; minET, 38.50 +/- 2.10/46.79 +/- 1.27; ETmax/op, 47.14 +/- 2.45/49.60 +/-
      1.57; temporal inferior area: 43.93 +/- 2.95/51.04 +/- 1.51 (all mean +/-
      standard deviation, MUm); R1, 0.76 +/- 0.09/0.93 +/- 0.04; R2, 1.08 +/- 0.04/1.21
      +/- 0.16; RTI/NS, 0.85 +/- 0.08/1.02 +/- 0.04; RI/S: 0.92 +/- 0.07/0.99 +/- 0.02.
      AUC values were R1: 0.979 (confidence interval [CI]: 0.957-1.000), RTI/NS: 0.977
      (CI: 0.951-1.000), and minET: 0.928 (CI: 0.880-0.977). CONCLUSIONS: Epithelial
      thickness maps could clearly visualize different ET patterns. Parameters with the
      highest potential of diagnostic discrimination between eyes with KC and healthy
      eyes were, in descending order, R1, RTI/NS, and minET. Consequently, epithelial
      thickness irregularity and asymmetry seem to be the most promising diagnostic
      factor in terms of discriminating between keratoconic eyes and healthy eyes.

PMID- 29458038
TI  - Diagnosing Distensible Venous Malformations of the Orbit With Diffusion-weighted
      Magnetic Resonance Imaging.
AB  - PURPOSE: To compare the diffusion-weighted imaging of nonthrombosed distensible
      venous malformations of the orbit with that of other histologically-proven
      orbital tumors. DESIGN: Retrospective case-control study. METHODS: Patients with
      nonthrombosed distensible venous malformations of the orbit and patients with
      other histologically-proven orbital tumors were selected for chart review. The
      main outcome measure was the apparent diffusion coefficient of these lesions.
      RESULTS: Sixty-seven patients qualified for chart review; 9 patients had
      nonthrombosed distensible venous malformations and 58 patients had other
      histologically-proven tumors. Three of the 9 patients with nonthrombosed
      distensible venous malformations were initially misdiagnosed as having had solid
      orbital tumors. The mean apparent diffusion coefficient of distensible venous
      malformations was 2.80 +/- 0.48 * 10-3 mm2/s, whereas the mean apparent diffusion
      coefficient of other histologically-proven tumors was 1.18 +/- 0.39 * 10-3 mm2/s
      (P < .001). The mean apparent diffusion coefficient ranged from 2.42 to 3.94 * 10
      3 mm2/s in the distensible venous malformation group, whereas other
      histologically-proven tumors ranged from 0.53 to 2.08 * 10-3 mm2/s. Therefore, in
      this single-institution series, a threshold value of 2.10 * 10-3 mm2/s was 100%
      sensitive and 100% specific for distensible venous malformations. CONCLUSION:
      Certain nonthrombosed distensible venous malformations can evade diagnostic
      suspicion and mimic solid orbital tumors on standard magnetic resonance imaging
      sequences. In this single-institution series, diffusion-weighted imaging
      effectively distinguished these nonthrombosed distensible venous malformations
      from other orbital tumors.

PMID- 29458039
TI  - Differential contribution of calcium channels to alpha1-adrenoceptor-mediated
      contraction is responsible for diverse responses to cooling between rat tail and
      iliac arteries.
AB  - Our previous studies have shown that alpha1-adrenoceptors, in addition to alpha2
      adrenoceptors, are involved in enhanced contraction of cutaneous blood vessels
      during cooling. The present study aimed to elucidate the mechanism underlying it.
      In tail and iliac arteries isolated from rats, isometric contraction was measured
      using a myograph and the phosphorylation level of myosin phosphatase target
      subunit 1 (MYPT1) was quantified by western blotting. The phenylephrine-induced
      contraction was enhanced by cooling to 24  degrees C in tail arteries, but was
      suppressed in iliac arteries. Endothelium denudation or treatment with
      iberiotoxin enhanced the phenylephrine-induced contraction in tail arteries at 37
      degrees C; however, neither affected the contraction at 24  degrees C. The
      phenylephrine-induced contraction at 37  degrees C was largely suppressed by
      nifedipine in iliac arteries, but only slightly in tail arteries. The Rho kinase
      inhibitor H-1152 largely suppressed the phenylephrine-induced contraction at 24 
      degrees C, but only slightly at 37  degrees C, in both arteries. The
      phosphorylation level of MYPT1 at Thr855 in tail arteries was increased by the
      cooling. Taken together, these results suggest the following mechanism in regard
      to cooling-induced enhancement of alpha1-adrenoceptor-mediated contraction in
      tail arteries: Cooling enhances the contraction of tail arteries via alpha1
      adrenoceptor stimulation by reducing endothelium-dependent, large-conductance
      Ca2+-activated K+ channel-mediated relaxation and by inducing Rho kinase-mediated
      Ca2+ sensitization, although the latter occurs even in iliac arteries. A smaller
      contribution of voltage-dependent Ca2+ channels, which are largely suppressed by
      cooling, to alpha1-adrenoceptor-mediated contraction in tail arteries seems to be
      more crucially involved in the appearance of the enhanced contractile response to
      cooling.

PMID- 29458036
TI  - Plasma amyloid levels within the Alzheimer's process and correlations with
      central biomarkers.
AB  - INTRODUCTION: Diagnostic relevance of plasma amyloid beta (Abeta) for Alzheimer's
      disease (AD) process yields conflicting results. The objective of the study was
      to assess plasma levels of Abeta42 and Abeta40 in amnestic mild cognitive
      impairment (MCI), nonamnestic MCI, and AD patients and to investigate
      relationships between peripheral and central biomarkers. METHODS: One thousand
      forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the
      Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk multicenter prospective
      study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance
      imaging assessments were included. RESULTS: Plasma Abeta1-42 and Abeta1-40 were
      lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9]
      and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL),
      respectively (P = .01 for overall difference between groups for Abeta1-42 and P =
      .04 for Abeta1-40). Globally, plasma Abeta1-42 correlated with age, Mini-Mental
      State Examination, and APOE epsilon4 allele. Plasma Abeta1-42 correlated with all
      CSF biomarkers in MCI but only with CSF Abeta42 in AD. DISCUSSION: Plasma Abeta
      was associated with cognitive status and CSF biomarkers, suggesting the interest
      of plasma amyloid biomarkers for diagnosis purpose.

PMID- 29458040
TI  - Pharmacological inhibition of JAK3 enhances the antitumor activity of imatinib in
      human chronic myeloid leukemia.
AB  - Imatinib (IMA) is the standard treatment for CML; however, stopping IMA sometimes
      results in disease relapse, which suggests that leukemic stem cells (LSCs) remain
      in such patients, even after complete molecular remission has been achieved.
      Therefore, new strategies will be required to eradicate LSCs. The Janus kinase
      signal transducer and activator of transcription (JAK-STAT) pathway is part of
      the BCR-ABL signaling network, and it is activated in CML, especially in LSCs.
      JAK2 is known to be associated with CML survival, but the role of JAK3 in CML
      remains unknown. The antitumor effects of IMA and a JAK3 inhibitor, tofacitinib
      were examined using the MTT assay in K562 and KCL22. To investigate the
      mechanisms of action of IMA and the JAK inhibitors in CML cells, we examined
      apoptosis, the cell cycle, and JAK-STAT signaling using flow cytometry,
      immunofluorescent microscopy, and Western blotting. The pharmacological
      inhibition of JAK3 by tofacitinib synergistically enhanced the antitumor effects
      of IMA in CML cells. Furthermore, the administration of IMA plus a JAK inhibitor
      reduced the expression of stem cells markers, such as ABCG2 and ALDH1A1. Co
      blocking JAK3 with IMA and a JAK3 inhibitor might represent a new treatment
      strategy for eradicating LSCs and preventing CML relapses.

PMID- 29458041
TI  - Role of superoxide ion formation in hypothermia/rewarming induced contractile
      dysfunction in cardiomyocytes.
AB  - Rewarming following accidental hypothermia is associated with circulatory
      collapse due primarily to impaired cardiac contractile (systolic) function.
      Previously, we found that reduced myofilament Ca2+ sensitivity underlies
      hypothermia/rewarming (H/R)-induced cardiac contractile dysfunction. This reduced
      Ca2+ sensitivity is associated with troponin I (cTnI) phosphorylation. We
      hypothesize that H/R induces reactive oxygen species (ROS) formation in
      cardiomyocytes, which leads to cTnI phosphorylation and reduced myofilament Ca2+
      sensitivity. To test this hypothesis, we exposed isolated rat cardiomyocytes to a
      2-h period of severe hypothermia (15  degrees C) followed by rewarming (35 
      degrees C) with and without antioxidant (TEMPOL) treatment. Simultaneous
      measurements of cytosolic Ca2+ ([Ca2+]cyto) and contractile (sarcomere
      shortening) responses indicated that H/R-induced contractile dysfunction and
      reduced Ca2+ sensitivity was prevented in cardiomyocytes treated with TEMPOL. In
      addition, TEMPOL treatment blunted H/R-induced cTnI phosphorylation. These
      results support our overall hypothesis and suggest that H/R disrupts excitation
      contraction coupling of the myocardium through a cascade of event triggered by
      excessive ROS formation during hypothermia. Antioxidant treatment may improve
      successful rescue of accidental hypothermia victims.

PMID- 29458042
TI  - Pretreatment with cholesterol-loaded cyclodextrins prevents loss of motility
      associated proteins during cryopreservation of addra gazelle (Nanger dama
      ruficollis) spermatozoa.
AB  - Sperm cryopreservation is challenging, often resulting in irreversible damage to
      spermatozoa, as indicated by decreased motility, viability, and/or acrosomal
      integrity. Developing cryopreservation protocols for gametes of endangered
      species compounds the complexity of technique optimization; samples are difficult
      to obtain and numbers are limited. Cryopreservation of sperm collected from the
      critically endangered addra gazelle (Nanger dama ruficollis), a member of the
      Bovidae family, resulted in significant loss of motility, which was prevented by
      pretreatment with cholesterol-loaded cyclodextrin (CLC). This study investigated
      the proteome of sperm (fresh and cryopreserved), processed in the absence and
      presence of 0.5 mg/ml CLC in the addra gazelle. The proteome of Bos taurus, the
      closest domestic relative, was used as a reference. Mass spectrometry analysis of
      the addra gazelle sperm proteome revealed 287 proteins. The concentrations of 85
      proteins differed between fresh and frozen/thawed samples; nearly all were
      decreased. Most were associated with metabolic processes, specifically
      glycolysis, which may explain the decrease in post-thaw motility observed in this
      species. CLC pretreatment partially prevented the loss of various proteins
      involved in metabolism including CAPZB (gene = CAPZB), HS90A (gene = HSP90AA1),
      and PGAM2 (gene = PGAM2). To our knowledge, this is the first study to evaluate
      the proteome of any wild bovids' sperm, and the first to compare protein levels
      in sperm pretreated with CLC.

PMID- 29458043
TI  - Optimization of a protective medium for enhancing the viability of freeze-dried
      Bacillus amyloliquefaciens B1408 based on response surface methodology.
AB  - Response surface methodology (RSM) is a commonly used system to optimize
      cryoprotectants of biocontrol strains when they are subjected to preparations.
      Various kinds of cryoprotectants and centrifugal conditions were tested to
      improve the survival of biocontrol agents after freeze-drying. To determine the
      optimum levels of incorporation of three cryoprotectants (glucose, trehalose and
      xylitol) in the freeze-drying process of strain Bacillus amyloliquefaciens B1408,
      a range of experiments based on Box-Behnken Design (BBD) were conducted. The
      results indicated that the suitable centrifugation conditions were 5000 r/min,10
      min and the optimum concentrations of cryoprotectants were glucose 1.00%,
      trehalose 4.74% and xylitol 1.45%. The proven survival rate of cells after freeze
      drying was 91.24%. These results convincingly demonstrated that freeze-drying
      could be used to preparation of biocontrol strain B1408. This study provides a
      theoretical basis for commercial possibilities and formulation development.

PMID- 29458044
TI  - Cryoprotective effect of antifreeze polyamino-acid (Carboxylated Poly-l-Lysine)
      on bovine sperm: A technical note.
AB  - In this study, investigating Carboxylated Poly-l-Lysine (CPLL) for its
      effectiveness as a new cryoprotectant for bovine sperm is aimed. CPLL is an
      ampholytic polymer compound, has cryoprotective properties similar to those of
      anti-freeze protein. The cryopreservation medium used for control group consisted
      of 6.5% (v/v) glycerol, the cryopreservation medium used for experimental group
      consisted of 3.25% (v/v) glycerol + 0.5% (w/v) CPLL. There was no consequential
      difference in sperm motility parameter after thawing whereas there was huge
      distinction for sperm membrane integrity rate (control vs experimental; 49.6 vs
      60.7%, P < 0.01). Conception rate of artificial insemination of experimental
      group was significantly higher than that of control group (79.0% vs 53.1%, P <
      0.01). These results suggest CPLL has protected sperm membrane and leads to
      improve fertility. This is the first report using CPLL for bovine sperm
      cryopreservation, it is also expected CPLL can be applied to other animal
      species.

PMID- 29458045
TI  - Aldose reductase inhibitor, fidarestat prevents doxorubicin-induced endothelial
      cell death and dysfunction.
AB  - Despite doxorubicin (Dox) being one of the most widely used chemotherapy agents
      for breast, blood and lung cancers, its use in colon cancer is limited due to
      increased drug resistance and severe cardiotoxic side effects that increase
      mortality associated with its use at high doses. Therefore, better adjuvant
      therapies are warranted to improve the chemotherapeutic efficacy and to decrease
      cardiotoxicity. We have recently shown that aldose reductase inhibitor,
      fidarestat, increases the Dox-induced colon cancer cell death and reduces
      cardiomyopathy. However, the efficacy of fidarestat in the prevention of Dox
      induced endothelial dysfunction, a pathological event critical to cardiovascular
      complications, is not known. Here, we have examined the effect of fidarestat on
      Dox-induced endothelial cell toxicity and dysfunction in vitro and in vivo.
      Incubation of human umbilical vein endothelial cells (HUVECs) with Dox
      significantly increased the endothelial cell death, and pre-treatment of
      fidarestat prevented it. Further, fidarestat prevented the Dox-induced oxidative
      stress, formation of reactive oxygen species (ROS) and activation of Caspase-3 in
      HUVECs. Fidarestat also prevented Dox-induced monocyte adhesion to HUVECs and
      expression of ICAM-1 and VCAM-1. Fidarestat pre-treatment to HUVECs restored the
      Dox-induced decrease in the Nitric Oxide (NO)-levels and eNOS expression.
      Treatment of HUVECs with Dox caused a significant increase in the activation of
      NF-kappaB and expression of various inflammatory cytokines and chemokines which
      were prevented by fidarestat pre-treatment. Most importantly, fidarestat
      prevented the Dox-induced mouse cardiac cell hypertrophy and expression of eNOS,
      iNOS, and 3-Nitrotyrosine in the aorta tissues. Further, fidarestat blunted the
      Dox-induced expression of various inflammatory cytokines and chemokines in vivo.
      Thus, our results suggest that by preventing Dox-induced endothelial cytotoxicity
      and dysfunction, AR inhibitors could avert cardiotoxicity associated with
      anthracycline chemotherapy.

PMID- 29458046
TI  - BMP-2 induces angiogenesis by provoking integrin alpha6 expression in human
      endothelial progenitor cells.
AB  - Bone morphogenetic protein-2 (BMP-2) is a multifunctional cytokine, capable of
      governing several cellular functions, including proliferation, motility,
      differentiation, and angiogenesis. Circulating endothelial progenitor cells
      (EPCs) have been shown to facilitate tissue repair, postnatal neovascularization,
      and tumor associated angiogenesis. Nevertheless, the impact of BMP-2 on
      angiogenesis of human EPCs has largely remained a mystery. In this study, we
      found that BMP-2 promoted cell migration and tube formation of EPCs in a
      concentration-dependent manner, indicating BMP-2 induced in vitro angiogenesis in
      human EPCs. Furthermore, BMP-2 significantly increased microvessel formation in
      Matrigel plug assay, and BMP-2 antagonist noggin prevented BMP-2-induced in vivo
      angiogenesis. Mechanistic investigations showed BMP-2 profoundly induced the
      expression of Id-1 and integrin alpha6 as well as EPCs angiogenesis by activating
      PI3K/Akt and MEK/ERK signaling pathways. Moreover, knockdown of Id-1 and integrin
      alpha6 by siRNA transfection obviously attenuated BMP-2-indueced tube formation
      of EPCs. These results suggest that BMP-2 promotes angiogenesis in human EPCs
      through the activation of PI3K/Akt, MEK/ERK, and Id-1/integrin alpha6 signaling
      cascades. This is the first demonstration that BMP-2 exhibits the angiogenesis
      property on human EPCs. BMP-2 might serve as the potential therapeutic target for
      treatment of angiogenesis-related diseases.

PMID- 29458048
TI  - 4-Phenylbutyric acid protects against lipopolysaccharide-induced bone loss by
      modulating autophagy in osteoclasts.
AB  - 4-Phenylbutyric acid (4-PBA) has been used clinically to treat urea cycle
      disorders and is known to be an inhibitor of endoplasmic reticulum (ER) stress.
      We hypothesized that 4-PBA attenuates inflammatory bone loss by inducing
      autophagy, a process that is frequently accompanied by ER stress. Micro
      computerized tomography analysis showed that 4-PBA attenuated LPS-induced bone
      loss in mice. The increased area of TRAP-positive osteoclasts (OCs) and serum
      level of collagen type I fragments in lipopolysaccharide (LPS)-treated mice were
      also decreased when 4-PBA was administered, suggesting a protective role of 4-PBA
      in OCs. In vitro, 4-PBA significantly reduced OC area without affecting the
      number of OCs induced by LPS and decreased bone resorption upon LPS stimulation.
      LPS-induced autophagy was attenuated by 4-PBA in OCs, as demonstrated by reduced
      LC3II accumulation, increased p62 level, and reduction in AVO-containing cells.
      Silencing of autophagy-related protein 7 attenuated the effects of 4-PBA on OC
      size and fusion. Moreover, 4-PBA reduced nuclear factor-kappaB (NF-kappaB) DNA
      binding upon LPS stimulation of OCs. Inhibition of NF-kappaB activation
      diminished the inhibitory effect of 4-PBA on LPS-stimulated changes in LC3II
      level, OC area, and OC fusion, implying that the effects of 4-PBA on OCs are due
      at least in part to inhibition of NF-kappaB. These data demonstrate that 4-PBA
      attenuates LPS-induced bone loss by reducing autophagy in OCs. Our data highlight
      the therapeutic potential of 4-PBA for ameliorating inflammatory bone loss.

PMID- 29458047
TI  - Effects of cytochrome P450 single nucleotide polymorphisms on methadone
      metabolism and pharmacodynamics.
AB  - Methadone is a synthetic, long-acting opioid with a single chiral center forming
      two enantiomers, (R)-methadone and (S)-methadone, each having specific
      pharmacological actions. Concentrations of (R)- and (S)-methadone above
      therapeutic levels have the ability to cause serious, life-threatening, and fatal
      side effects. This toxicity can be due in part to the pharmacogenetics of an
      individual, which influences the pharmacokinetic and pharmacodynamic properties
      of the drug. Methadone is primarily metabolized in the liver by cytochrome P450
      (CYP) enzymes, predominately by CYP2B6, followed by CYP3A4, 2C19, 2D6, and to a
      lesser extent, CYP2C18, 3A7, 2C8, 2C9, 3A5, and 1A2. Single nucleotide
      polymorphisms (SNPs) located within CYPs have the potential to play an important
      role in altering methadone metabolism and pharmacodynamics. Several SNPs in the
      CYP2B6, 3A4, 2C19, 2D6, and 3A5 genes result in increases in methadone plasma
      concentrations, decreased N-demethylation, and decreased methadone clearance. In
      particular, carriers of CYP2B6*6/*6 may have a greater risk for detrimental
      adverse effects, as methadone metabolism and clearance are diminished in these
      individuals. CYP2B6*4, on the other hand, has been observed to decrease plasma
      concentrations of methadone due to increased methadone clearance. The
      involvement, contribution, and understanding the role of SNPs in CYP2B6, and
      other CYP genes, in methadone metabolism can improve the therapeutic uses of
      methadone in patient outcome and the development of personalized medicine.

PMID- 29458049
TI  - A comprehensive BRCA1/2 NGS pipeline for an immediate Copy Number Variation (CNV)
      detection in breast and ovarian cancer molecular diagnosis.

PMID- 29458050
TI  - Investigation of metabolic stability of the novel ALK inhibitor brigatinib by
      liquid chromatography tandem mass spectrometry.
AB  - Brigatinib (BGB) belongs to a class of drugs called ALK inhibitor. On April 28,
      2017, BGB has been approved by U.S. FDA for use in metastatic ALK-positive NSCLC.
      A fast, specific, sensitive and validated LC-MS/MS method was developed for the
      quantification of BGB in human plasma matrix. This method was applied
      successfully to study metabolic stability of BGB. Reversed phase (C18 column) and
      isocratic binary mobile phase (55% 0.1% formic acid: 45% ACN) were used for
      chromatographic separation of BGB and ponatinib (IS). The flow rate, total run
      time and injection volume were fixed at 0.2 mL/min, 4 min, 5 MUL respectively.
      ESI source was utilized for ions formation, while multiple reaction monitoring
      (MRM) mode was used for ion analysis. In human plasma matrix, the Linearity range
      of the calibration curve was 5-500 ng/mL (r2 >= 0.9982). LOQ and LOD were found
      to be 1.89 and 5.72 ng/mL. The precision and accuracy for the intra-day and inter
      day were 0.45 to 1.85% and 97.37 to 104.85%. In vitro half-life (t1/2) and
      intrinsic clearance (CLint) were equal to 12.0 min and 13.1 +/- 0.15 mL/min/kg
      respectively. The quantification of BGB in human plasma or its metabolic
      stability has not been studied as seen in literature review.

PMID- 29458051
TI  - Elevated systemic zonula occludens 1 is positively correlated with inflammation
      in cirrhosis.
AB  - BACKGROUND/AIM: It has been well established that disruption of the intestinal
      barrier function and increased intestinal permeability contribute to endotoxemia
      and associated liver injury in patients with cirrhosis. However, the relationship
      between systemic inflammation and tight junction protein in cirrhosis remain
      unidentified. The aim of this study was to assess and compare the blood
      concentrations of ZO-1 with systemic hsCRP in patients with cirrhosis and healthy
      individuals. METHODS: 30 cirrhotic patients and 30 healthy individuals were
      enrolled in the study. Blood ZO-1 and hsCRP were measured by ELISA and
      biochemical parameters by AU680 Beckman Coulter (USA) autoanalyser. RESULTS: The
      serum ALT, AST, bilirubin, gamma GT, ALP and ammonia were significantly (P <
      0.0001) elevated whilst serum albumin concentration was decreased in cirrhotic
      patients when compared to healthy individuals. Systemic tight junction protein ZO
      1 concentration [590.0 +/- 32.79 vs. 349.9 +/- 18.76 pg/ml, respectively; P <
      0.0001] and hsCRP [10.50 +/- 1.05 vs 5.31 +/- 0.65 mg/L, respectively; P < 0.001]
      were significantly elevated in patients with cirrhosis compared to controls.
      Significant positive correlation was found between increased ZO-1 and hsCRP (r =
      0.2680 P < 0.01). CONCLUSION: Our results suggested that increased systemic ZO-1
      concentration was associated with inflammation in cirrhosis. Thus, elevated blood
      ZO-1 levels could be a prognostic marker of cirrhotic patients with intestinal TJ
      disruption on the background of inflammation.

PMID- 29458052
TI  - Regulation of proliferation and functioning of transplanted cells by using herpes
      simplex virus thymidine kinase gene in mice.
AB  - Though cell transplantation is becoming an attractive therapeutic method,
      uncontrolled cell proliferation or overexpression of cellular functions could
      cause adverse effects. These unfavorable outcomes could be avoided by regulating
      the proliferation or functioning of transplanted cells. In this study, we used a
      combination of the herpes simplex virus thymidine kinase (HSVtk) gene, a suicide
      gene, and ganciclovir (GCV) to control the proliferation and functioning of
      insulin-secreting cells after transplantation in diabetic mice. Mouse pancreatic
      beta cell line MIN6 cells were selected as insulin-secreting cells for
      transfection with the HSVtk gene to obtain MIN6/HSVtk cells. Proliferation of
      MIN6/HSVtk cells was suppressed by GCV in a concentration-dependent manner; 0.25
      MUg/mL GCV maintained a constant number of MIN6/HSVtk cells for at least 16 days.
      MIN6 or MIN6/HSVtk cells were then transplanted to streptozotocin-induced
      diabetic mice. Mice transplanted with MIN6 cells exhibited hypoglycemia
      irrespective of GCV administration. In contrast, normal (around 150 mg/dL) blood
      glucose levels were maintained in mice transplanted with MIN6/HSVtk cells by a
      daily administration of 50 mg/kg of GCV. These results indicate that controlling
      the proliferation and functioning of HSVtk gene-expressing cells by GCV could
      greatly improve the usefulness and safety of cell-based therapy.

PMID- 29458053
TI  - Circulating bile acids in healthy adults respond differently to a dietary pattern
      characterized by whole grains, legumes and fruits and vegetables compared to a
      diet high in refined grains and added sugars: A randomized, controlled, crossover
      feeding study.
AB  - OBJECTIVE: The effects of diets high in refined grains on biliary and colonic
      bile acids have been investigated extensively. However, the effects of diets high
      in whole versus refined grains on circulating bile acids, which can influence
      glucose homeostasis and inflammation through activation of farnesoid X receptor
      (FXR) and G protein-coupled bile acid receptor 1 (TGR5), have not been studied.
      MATERIALS AND METHODS: We conducted a secondary analysis from a randomized
      controlled crossover feeding trial (NCT00622661) in 80 healthy adults (40
      women/40 men, age 18-45 years) from the greater Seattle Area, half of which were
      normal weight (BMI 18.5-25.0 kg/m2) and half overweight to obese (BMI 28.0-39.9
      kg/m2). Participants consumed two four-week controlled diets in randomized order:
      1) a whole grain diet (WG diet), designed to be low in glycemic load (GL), high
      in whole grains, legumes, and fruits and vegetables, and 2) a refined grain diet
      (RG diet), designed to be high GL, high in refined grains and added sugars,
      separated by a four-week washout period. Quantitative targeted analysis of 55
      bile acid species in fasting plasma was performed using liquid chromatography
      tandem mass spectrometry. Concentrations of glucose, insulin, and CRP were
      measured in fasting serum. Linear mixed models were used to test the effects of
      diet on bile acid concentrations, and determine the association between plasma
      bile acid concentrations and HOMA-IR and CRP. Benjamini-Hochberg false discovery
      rate (FDR) < 0.05 was used to control for multiple testing. RESULTS: A total of
      29 plasma bile acids were reliably detected and retained for analysis.
      Taurolithocholic acid (TLCA), taurocholic acid (TCA) and glycocholic acid (GCA)
      were statistically significantly higher after the WG compared to the RG diet (FDR
      < 0.05). There were no significant differences by BMI or sex. When evaluating the
      association of bile acids and HOMA-IR, GCA, taurochenodeoxycholic acid,
      ursodeoxycholic acid (UDCA), 5beta-cholanic acid-3beta,12alpha-diol, 5-cholanic
      acid-3beta-ol, and glycodeoxycholic acid (GDCA) were statistically significantly
      positively associated with HOMA-IR individually, and as a group, total, 12alpha
      hydroxylated, primary and secondary bile acids were also significant (FDR <
      0.05). When stratifying by BMI, chenodeoxycholic acid (CDCA), cholic acid (CA),
      UDCA, 5beta-cholanic acid-3beta, deoxycholic acid, and total, 12alpha
      hydroxylated, primary and secondary bile acid groups were significantly
      positively associated with HOMA-IR among overweight to obese individuals (FDR <
      0.05). When stratifying by sex, GCA, CDCA, TCA, CA, UDCA, GDCA, glycolithocholic
      acid (GLCA), total, primary, 12alpha-hydroxylated, and glycine-conjugated bile
      acids were significantly associated with HOMA-IR among women, and CDCA, GDCA, and
      GLCA were significantly associated among men (FDR < 0.05). There were no
      significant associations between bile acids and CRP. CONCLUSIONS: Diets with
      comparable macronutrient and energy composition, but differing in carbohydrate
      source, affected fasting plasma bile acids differently. Specifically, a diet
      characterized by whole grains, legumes, and fruits and vegetables compared to a
      diet high in refined grains and added sugars led to modest increases in
      concentrations of TLCA, TCA and GCA, ligands for FXR and TGR5, which may have
      beneficial effects on glucose homeostasis.

PMID- 29458054
TI  - Comparative investigation of binding interactions with three steroidal
      derivatives of d(GGGT)4 G-quadruplex aptamer.
AB  - Steroidal derivatives have attracted tremendous attentions in biological and
      biomedical areas, due to their variety biological activities. The investigation
      of structural influences helps in understanding their biological activities. The
      interactions of steroidal derivatives with DNA may play important roles in
      biological activities, however only a few investigations were reported on this
      issue. Herein, the structural influences of three steroidal derivatives were
      investigated based on their binding interactions with d(GGGT)4 G-quadruplex
      aptamer by spectroscopic approaches, nuclear magnetic resonance (NMR),
      electrochemical methods, and molecular modeling techniques. Three compounds were
      found to selectively bind with parallel G-quadruplex aptamer to form three
      complexes through end-stacking binding modes. Three compounds stabilized the G
      quadruplex structure of the aptamer at different levels, which enhanced the
      biological activity of this aptamer to some extent. The space steric hindrance
      was responsible for differences in the binding interactions between d(GGGT)4 G
      quadruplex aptamer and three compounds. These results provide new information for
      the molecular understanding of binding interactions of steroidal derivatives with
      DNA and the strategy for research of structural influences.

PMID- 29458055
TI  - Brain activation associated to olfactory conditioned same-sex partner preference
      in male rats.
AB  - Sexual preferences can be strongly modified by Pavlovian learning. For instance,
      olfactory conditioned same-sex partner preference can occur when a sexually naive
      male cohabits with an scented male during repeated periods under the effects of
      enhanced D2-type activity. Preference is observed days later via social and
      sexual behaviors. Herein we explored brain activity related to learned same-sex
      preference (Fos-Immunoreactivity, IR) following exposure to a conditioned odor
      paired with same-sex preference. During conditioning trials males received either
      saline or the D2-type receptor agonist quinpirole (QNP) and cohabitated during 24
      h with a stimulus male that bore almond scent on the back as conditioned
      stimulus. This was repeated every 4 days, for a total of three trials. In a drug
      free final test we assessed socio/sexual partner preference between the scented
      male and a receptive female. The results indicated that QNP-conditioned males
      developed a same-sex preference observed via contact, time spent, olfactory
      investigations, and non-contact erections. By contrast, saline-conditioned and
      intact (non-exposed to conditioning) males expressed an unconditioned preference
      for the female. Four days later the males were exposed to almond scent and their
      brains were processed for Fos-IR. Results indicated that the QNP-conditioned
      group expressed more Fos-IR in the nucleus accumbens (AcbSh), medial preoptic
      area (MPA), piriform cortex (Pir) and ventromedial nucleus of the hypothalamus
      (VMH) as compared to saline-conditioned. Intact males expressed the lowest Fos-IR
      in AcbSh and VMH, but the highest in MPA and Pir. We discuss the role of these
      areas in the learning process of same-sex partner preferences and olfactory
      discrimination.

PMID- 29458057
TI  - Roles of the insulin signaling pathway in insect development and organ growth.
AB  - Organismal development is a complex process as it requires coordination of many
      aspects to grow into fit individuals, such as the control of body size and organ
      growth. Therefore, the mechanisms of precise control of growth are essential for
      ensuring the growth of organisms at a correct body size and proper organ
      proportions during development. The control of the growth rate and the duration
      of growth (or the cessation of growth) are required in size control. The insulin
      signaling pathway and the elements involved are essential in the control of
      growth. On the other hand, the ecdysteroid molting hormone determines the
      duration of growth. The secretion of these hormones is controlled by
      environmental factors such as nutrition. Moreover, the target of rapamycin (TOR)
      pathway is considered as a nutrient sensing pathway. Important cross-talks have
      been shown to exist among these pathways. In this review, we outline the control
      of body and organ growth by the insulin/TOR signaling pathway, and also the
      interaction between nutrition via insulin/TOR signaling and ecdysteroids at the
      coordination of organismal development and organ growth in insects, mainly
      focusing on the well-studied fruit fly Drosophila melanogaster.

PMID- 29458056
TI  - Alcohol and CV Health: Jekyll and Hyde J-Curves.
AB  - A routine of light or moderate alcohol consumption (<=1 drink/day for women and 1
      to 2 drinks/day for men) is associated with a lower risk for all-cause mortality,
      coronary artery disease (CAD), type 2 diabetes mellitus (T2D), heart failure
      (HF), and stroke. Conversely, heavy drinking, (>4 drinks/day) is associated with
      an increased risk for death and cardiovascular (CV) disease (CVD). Excessive
      alcohol intake trails behind only smoking and obesity among the 3 leading causes
      of premature deaths in the United States (US). Heavy alcohol use is a common
      cause of reversible hypertension (HTN), nonischemic dilated cardiomyopathy,
      atrial fibrillation (AF), and stroke (both ischemic and hemorrhagic). Among males
      aged 15 to 59 years, alcohol abuse is perhaps the leading cause of premature
      death. As such, the risk-to-benefit ratio of drinking is less favorable in
      younger individuals. A daily habit of light to moderate drinking is ideal for
      those who choose to consume alcohol regularly. Red wine in particular before or
      during the evening meal is linked with the best long-term CV outcomes. Most of
      the studies on alcohol and health are observational, and correlation does not
      prove causation. Health care professionals should not advise nondrinkers to begin
      drinking because of the paucity of randomized outcome data coupled with the
      potential for alcohol abuse even among seemingly low risk individuals.

PMID- 29458058
TI  - Lithium modulates the muscarinic facilitation of synaptic plasticity and theta
      gamma coupling in the hippocampal-prefrontal pathway.
AB  - Mood disorders are associated to functional unbalance in mesolimbic and frontal
      cortical circuits. As a commonly used mood stabilizer, lithium acts through
      multiple biochemical pathways, including those activated by muscarinic
      cholinergic receptors crucial for hippocampal-prefrontal communication.
      Therefore, here we investigated the effects of lithium on prefrontal cortex
      responses under cholinergic drive. Lithium-treated rats were anesthetized with
      urethane and implanted with a ventricular cannula for muscarinic activation, a
      recording electrode in the medial prefrontal cortex (mPFC), and a stimulating
      electrode in the intermediate hippocampal CA1. Either of two forms of synaptic
      plasticity, long-term potentiation (LTP) or depression (LTD), were induced during
      pilocarpine effects, which were monitored in real time through local field
      potentials. We found that lithium attenuates the muscarinic potentiation of
      cortical LTP (<20 min) but enhances the muscarinic potentiation of LTD
      maintenance (>80 min). Moreover, lithium treatment promoted significant cross
      frequency coupling between CA1 theta (3-5 Hz) and mPFC low-gamma (30-55 Hz)
      oscillations. Interestingly, lithium by itself did not affect any of these
      measures. Thus, lithium pretreatment and muscarinic activation synergistically
      modulate the hippocampal-prefrontal connectivity. Because these alterations
      varied with time, oscillatory parameters, and type of synaptic plasticity, our
      study suggests that lithium influences prefrontal-related circuits through
      intricate dynamics, informing future experiments on mood disorders.

PMID- 29458059
TI  - Modest enhancement of sensory axon regeneration in the sciatic nerve with
      conditional co-deletion of PTEN and SOCS3 in the dorsal root ganglia of adult
      mice.
AB  - Axons within the peripheral nervous system are capable of regeneration, but full
      functional recovery is rare. Recent work has shown that conditional deletion of
      two key signaling inhibitors of the PI3K and Jak/Stat pathways-phosphatase and
      tensin homolog (PTEN) and suppressor of cytokine signaling-3 (SOCS3),
      respectively-promotes regeneration of normally non-regenerative central nervous
      system axons. Moreover, in studies of optic nerve regeneration, co-deletion of
      both PTEN and SOCS3 has an even greater effect. Here, we test the hypotheses (1)
      that PTEN deletion enhances axon regeneration following sciatic nerve crush and
      (2) that PTEN/SOCS3 co-deletion further promotes regeneration. PTENfl/fl and
      PTEN/SOCS3fl/fl mice received direct injections of AAV-Cre into the fourth and
      fifth lumbar dorsal root ganglia (DRG) two weeks prior to sciatic nerve crush.
      Western blot analysis of whole cell lysates from DRG using phospho-specific
      antibodies revealed that PTEN deletion did not enhance or prolong PI3K signaling
      following sciatic nerve crush. However, PTEN/SOCS3 co-deletion activated PI3K for
      at least 7 days post-injury in contrast to controls, where activation peaked at 3
      days. Quantification of SCG10-expressing regenerating sensory axons in the
      sciatic nerve after crush injury revealed longer distance regeneration at 3 days
      post-injury with both PTEN and PTEN/SOCS3 co-deletion. Additionally, analysis of
      noxious thermosensation and mechanosensation with PTEN/SOCS3 co-deletion revealed
      enhanced sensation at 14 and 21 days after crush, respectively, after which all
      treatment groups reached the same functional plateau. These findings indicate
      that co-deletion of PTEN and SOCS3 results in modest but measureable enhancement
      of early regeneration of DRG axons following crush injury.

PMID- 29458060
TI  - Crim1 is required for maintenance of the ocular lens epithelium.
AB  - The development and growth of the vertebrate ocular lens is dependent on the
      regulated proliferation of an anterior monolayer of epithelial cells, and their
      subsequent differentiation into elongate fiber cells. The growth factor rich
      ocular media that bathes the lens mediates these cellular processes, and their
      respective intracellular signaling pathways are in turn regulated to ensure that
      the proper lens architecture is maintained. Recent studies have proposed that
      Cysteine Rich Motor Neuron 1 (Crim1), a transmembrane protein involved in
      organogenesis of many tissues, might influence cell adhesion, polarity and
      proliferation in the lens by regulating integrin-signaling. Here, we characterise
      the lens and eyes of the Crim1KST264 mutant mice, and show that the loss of Crim1
      function in the ocular tissues results in inappropriate differentiation of the
      lens epithelium into fiber cells. Furthermore, restoration of Crim1 levels in
      just the lens tissue of Crim1KST264 mice is sufficient to ameliorate most of the
      dysgenesis observed in the mutant animals. Based on our findings, we propose that
      tight regulation of Crim1 activity is required for maintenance of the lens
      epithelium, and its depletion leads to ectopic differentiation into fiber cells,
      dramatically altering lens structure and ultimately leading to microphthalmia and
      aphakia.

PMID- 29458061
TI  - Decreased MCP-1/CCR2 axis-mediated chemotactic effect of conjunctival fibroblasts
      after transdifferentiation into myofibroblasts.
AB  - The purpose of this study is to investigate the change in chemotactic effects of
      human conjunctival fibroblasts (HConFs) after transdifferentiation into
      myofibroblasts, and to explore related molecular mechanisms. HConFs were treated
      with 5 ng/mL transforming growth factor (TGF)-beta2 for 48 h to induce
      transdifferentiation into myofibroblasts. The cytokine concentrations in the
      conditioned media of HConFs were measured by multiplex bead-based immunoassays.
      The Boyden chamber assay was used to assess the chemotactic effects using the
      monocyte cell line, THP-1 cells. The concentration of monocyte chemoattractant
      protein (MCP)-1 in the conditioned media was decreased after transdifferentiation
      into myofibroblasts (P < 0.001). The conditioned media of HConFs exerted a
      chemotactic effect on THP-1 cells, but this effect decreased after
      transdifferentiation into myofibroblasts (P = 0.032). The number of migrated THP
      1 cells decreased significantly upon treatment with neutralizing anti-MCP-1
      antibodies (P = 0.006) and tended to decrease upon treatment with C-C chemokine
      receptor (CCR) 2 antagonist. The chemotactic effect of HConFs mediated by the MCP
      1/CCR2 axis was decreased after transdifferentiation into myofibroblasts.

PMID- 29458062
TI  - An Unexpected Degradation Pathway of a 1,2,4-Triazolo[4,3-a]pyridine Derivative:
      The Formation of 2 Cationic Pseudodimers of an 11beta-Hydroxysteroid
      Dehydrogenase Type 1 Inhibitor Drug Candidate in a Stressed Capsule Formulation.
AB  - Degradation of an active pharmaceutical ingredient (API), a 2-(3-(1-(4
      chlorophenyl)cyclopropyl)-[1,2,4]triazolo[4,3-a]pyridin-8-yl)propan-2-ol
      hydrochloride salt, was observed in a capsule formulation stressed at 50 degrees
      C or 40 degrees C/75% relative humidity conditions for 1 month. Two unknown
      degradants were identified as cationic pseudodimers of the API via accurate mass
      liquid chromatography-mass spectrometry and 1- and 2-dimensional NMR analyses. A
      plausible degradation pathway of the API was postulated which led to the
      identification of 2 key N-oxide degradants in the stressed capsule formulation at
      trace levels. It was hypothesized that the N-oxide degradants could be protonated
      and undergo further transformation so as to react with another API free base to
      form pseudodimeric N-oxide intermediates, followed by protonation/dehydration to
      yield the cationic pseudodimers of the API. The proposed degradation pathway was
      further supported by formulation screening studies: (1) the removal of magnesium
      stearate (base/lubricant) from the formulation to reduce the formation of API
      free base, which is susceptible to oxidation to form N-oxides; (2) the
      replacement of API hydrochloride salt by its free base form to eliminate the
      proton source for protonation of the N-oxides so as to prevent their further
      transformation; and (3) the addition of anti-oxidants to minimize the oxidation
      of API free base to N-oxides.

PMID- 29458063
TI  - Ventilator-associated events as a quality indicator in intensive care units.

PMID- 29458064
TI  - Estimating the additional costs of surgical site infections: length bias, time
      dependent bias, and conditioning on the future.

PMID- 29458065
TI  - Nosocomial ventriculitis caused by a meticillin- and linezolid-resistant clone of
      Staphylococcus epidermidis in neurosurgical patients.
AB  - BACKGROUND: Postneurosurgical ventriculitis is mainly caused by coagulase
      negative staphylococci. The rate of linezolid-resistant Staphylococcus
      epidermidis (LRSE) is increasing worldwide. AIMS: To report clinical,
      epidemiological and microbiological data from a series of ventriculitis cases
      caused by LRSE in a Spanish hospital between 2013 and 2016. METHODS: Cases of
      LRSE ventriculitis were reviewed retrospectively in a Spanish hospital over a
      four-year period. Clinical/epidemiological data of the infected patients were
      reviewed, the isolates involved were typed by pulsed-field gel electrophoresis
      (PFGE) and multi-locus sequence typing, and the molecular bases of linezolid
      resistance were determined. FINDINGS: Five cases of LRSE ventriculitis were
      detected. The patients suffered from cerebral haemorrhage or head trauma that
      required the placement of an external ventricular drain; spent a relatively long
      time in the intensive care unit (ICU) (10-26 days); and three out of the five
      patients had previously been treated with linezolid. All LRSE had the same PFGE
      pattern, belonged to ST2, and shared an identical mechanism of linezolid
      resistance. Specifically, all had the G2576T mutation in the V domain of each of
      the six copies of the 23S rRNA gene, together with the Q136L and M156T mutations
      and the 71GGR72 insertion in the L3 and L4 ribosomal proteins, respectively.
      CONCLUSION: The high ratio of linezolid consumption in the ICU (7.72-8.10 defined
      daily dose/100 patient-days) could have selected this resistant clone, which has
      probably become endemic in the ICU where it could have colonized admitted
      patients. Infection control and antimicrobial stewardship interventions are
      essential to prevent the dissemination of this difficult-to-treat pathogen, and
      to preserve the therapeutic efficacy of linezolid.

PMID- 29458066
TI  - Volitional Voiding of the Bladder after Spinal Cord Injury: Validation of
      Bilateral Lower Extremity Motor Function as a Key Predictor.
AB  - PURPOSE: In many individuals with spinal cord injury a return of volitional
      bladder voiding is considered more important than regaining motor function.
      Recently a predictive model using only composite bilateral lower extremity motor
      scores for levels L2-S1 (range 0 to 50) was proposed by the EMSCI (European
      Multicenter Study about Spinal Cord Injury) group. The model showed exceptional
      predictive power with an AUC of 0.912. We sought to further validate the EMSCI
      model in a national spinal cord injury cohort. MATERIALS AND METHODS: We created
      models of volitional voiding using the United States NSCID (National Spinal Cord
      Injury Database) for 2007 to 2016. In addition to testing lower extremity motor
      scores, we evaluated other patient variables that we hypothesized might affect
      volitional voiding. RESULTS: Volitional voiding was present in 1,333 of the
      cohort of 4,327 individuals (30.8%) at 1-year followup. While younger age, female
      gender, increased sacral sparing, improved AIS (American Spinal Injury
      Association Impairment Scale) classification and a more caudal sensory level
      predicted volitional voiding, lower extremity motor scores were most predictive
      (AUC 0.919). Adding the other patient characteristics did little to improve model
      performance (full model AUC 0.932). Further analysis of the predictive power of
      lower extremity motor scores suggested that while the AUC appeared to decrease in
      persons who were most likely to void volitionally, the performance of the
      predictive model remained outstanding with a combined AIS C and D AUC of 0.792.
      CONCLUSIONS: Our study verifies the validity of the EMSCI predictive model of
      volitional voiding after spinal cord injury. The differing performance of lower
      extremity motor scores in various AIS classifications should be noted.

PMID- 29458067
TI  - Fluctuations of extracellular glucose and lactate in the mouse primary visual
      cortex during visual stimulation.
AB  - We measured the extracellular glucose and lactate in the primary visual cortex in
      the CD-1 mouse using electrochemical electrodes. To gain some additional
      information on brain metabolism, we examined the impact of systemic injections of
      lactate and fructose on the brain extracellular glucose and lactate changes
      observed during visual stimulation. We found that simple stimulation using a
      flashlight produced a decrease in visual cortex extracellular glucose and an
      increase in extracellular lactate. Similar results were observed following visual
      stimulation with an animated movie without soundtrack or the presentation of a
      novel object. Specificity of these observations was confirmed by the absence of
      extracellular glucose and lactate changes when the mice were presented a second
      time with the same object. Previous experiments have shown that systemic
      injections of fructose and lactate lead to an increase in blood lactate but no
      change in blood glucose while they both increase brain extracellular glucose but
      they do not increase brain extracellular lactate. When mice were visually
      stimulated after they had received these injections, we found that lactate, and
      to a slightly lesser degree fructose, both reduced the amplitude of the changes
      in extracellular glucose and lactate that accompanied visual stimulation. Thus,
      neural activation leads to an increase in extracellular lactate and a decrease in
      extracellular glucose. Novelty, attentional resources and availability of
      metabolic fuels modulate these fluctuations. The observations are consistent with
      a modified view of brain metabolism that takes into account the blood and brain
      glucose availability.

PMID- 29458068
TI  - Ovarian microcystic stromal tumor with undetermined potential: case study with
      molecular analysis and literature review.
AB  - Ovarian microcystic stromal tumor is a relatively rare tumor type. This tumor is
      characterized by a unique microcyst structure, and essentially all tumors show
      benign biological behavior. Here, we report a case with a primary ovarian
      microcystic stromal tumor that experienced recurrence. Pathological findings
      showed that the original tumor, relapsed tumor in the ovary, and the recurrent
      tumor in the iliac fossa presented similar histologic features. The tumor mainly
      consisted of microcysts, solid cellular regions, and a fibrous stroma.
      Immunohistochemically, the tumor cells were positive for beta-catenin, CD10,
      vimentin, and WT-1. Mutational analysis revealed a missense mutation (c.1590C>T;
      pG530E) in exon 15 of the APC gene and another missense mutation (c.740G>A;
      pA247V) in exon 1 of the KRAS gene. We also reviewed other published cases to
      evaluate the prognosis and treatment. This is the first report to describe a
      microcystic stromal tumor of the ovary presenting with undetermined biological
      potential.

PMID- 29458069
TI  - High expression of NPRL2 is linked to poor prognosis in patients with prostate
      cancer.
AB  - As a tumor suppressor candidate gene, NPRL2 has anticancer effects against
      several cancers, but its potential role in prostate cancer (PCa) has not been
      reported. The present study aimed to explore the expression of NPRL2 in PCa and
      its potential clinical significance. Our results showed that expression of NPRL2
      in PCa tissues was significantly higher than that in non-PCa tissues (P < .001).
      High NPRL2 expression in PCa tissue was significantly correlated with a high
      Gleason grade group (P < .001), high pT stage (P < .001), and lymph node
      metastasis (P = .003). The overall survival of PCa patients with negative to weak
      NPRL2 expression was significantly higher than that of patients with moderate to
      strong positive NPRL2 expression. Furthermore, in vitro, we found that the up
      regulated NPRL2 level in LNCaP and PC3 cells, and forced reexpression of NPRL2
      significant promoted the growth of those cells and vice versa. Contrary to
      existing reports, our results interestingly showed, for the first time, that the
      expression level of NPRL2 was significantly up-regulated in PCa and its high
      expression was correlated with poor prognosis, suggesting its pivotal role in the
      progression of PCa. NPRL2 may serve as a potential prognostic biomarker for PCa
      patients.

PMID- 29458070
TI  - The epigenetic alterations of endogenous retroelements in aging.
AB  - Endogenous retroelements, transposons that mobilize through RNA intermediates,
      include some of the most abundant repetitive sequences of the human genome, such
      as Alu and LINE-1 sequences, and human endogenous retroviruses. Recent
      discoveries demonstrate that these mobile genetic elements not only act as
      intragenomic parasites, but also exert regulatory roles in living cells. The risk
      of genomic instability represented by endogenous retroelements is normally
      counteracted by a series of epigenetic control mechanisms which include, among
      the most important, CpG DNA methylation. Indeed, most of the genomic CpG sites
      subjected to DNA methylation in the nuclear DNA are carried by these repetitive
      elements. As other parts of the genome, endogenous retroelements and other
      transposable elements are subjected to deep epigenetic alterations during aging,
      repeatedly observed in the context of organismal and cellular senescence, in
      human and other species. This review summarizes the current status of knowledge
      about the epigenetic alterations occurring in this large, non-genic portion of
      the genome in aging and age-related conditions, with a focus on the causes and
      the possible functional consequences of these alterations.

PMID- 29458071
TI  - B cells in operational tolerance.
AB  - Transplantation is currently the therapy of choice for endstage organ failure
      even though it requires long-term immunosuppresive therapy, with its numerous
      side effects, for acceptance of the transplanted organ. In rare cases however,
      patients develop operational tolerance, that is, graft survival without
      immunosuppression. Studies conducted on these patients reveal genetic,
      phenotypic, and functional signatures. They provide a better understanding of the
      immunological mechanisms involved in operational tolerance and define biomarkers
      that could be used to adapt immunosuppressive treatment to the individual, safely
      reduce immunosuppression doses, and ideally and safely guide immunosuppression
      withdrawal. This review summarizes studies that suggest a role for B cells as
      biomarkers of operational tolerance and discusses the use of B cells as a
      predictive tool for immunologic risk.

PMID- 29458072
TI  - Influence of Xenorhabdus (Gamma-Proteobacteria: Enterobacteriaceae) symbionts on
      gonad postembryonic development in Steinernema (Nematoda: Steinernematidae)
      nematodes.
AB  - Steinernema nematodes and their Xenorhabdus partners form an obligate mutualistic
      association. This partnership is insecticidal to a wide range of insects.
      Steinernema rely on their Xenorhabdus partner to produce toxins inside the insect
      cadaver to liberate nutrients from the insect, as well as antimicrobials to
      sterilize the cadaver, thus creating a suitable environment for reproduction. In
      return, Steinernema vector their Xenorhabdus between insect hosts. Disruption of
      this partnership may affect the success of both partners. For instance, when
      Steinernema associates with non-cognate symbionts, their virulence and
      reproductive fitness are affected. In this study, we examined the effect of
      symbiotic (cognate and non-cognate) and non-symbiotic bacteria on maturation
      time, gonad postembryonic development, and sex ratio of first-generation
      Steinernema adults. Two Steinernema spp. were considered: S. feltiae SN and S.
      carpocapsae All. In vitro assays were carried out by pairing each nematode sp.
      with symbiotic (cognate and non-cognate) Xenorhabdus, and with non-symbiotic
      bacteria (Serratia proteamaculans). Additionally, for comparative purposes, we
      also considered adult nematodes reared in vivo in Galleria mellonella larvae to
      assess nematode development under natural conditions. Results from this study
      showed non-symbiotic Serratia proteamaculans did not support adult development of
      S. feltiae but it allowed development of S. carpocapsae adults. Sex ratio
      decreased from 2:1 to 1:1 (female: male) when S. carpocapsae adults were reared
      with the non-symbiotic S. proteamaculans. Cognate or non-cognate Xenorhabdus spp.
      and/or strains did not change the sex ratio of any of either Steinernema spp.
      tested. Morphometric analysis also revealed that bacterial conditions influenced
      adult size and gonad postembryonic development in both Steinernema species. Body
      size (length and width), and gonad length in both S. feltiae males and females,
      were significantly reduced when reared with a non-cognate Xenorhabdus species. In
      S. carpocapsae, males exhibited an enhanced body size (length and width) and
      gonad length when reared with a non-cognate X. nematophila strain. S. carpocapsae
      females also exhibited an enhanced gonad length when reared with a non-cognate X.
      nematophila strain. S. carpocapsae males and females were underdeveloped when
      reared with the non-symbiotic S. proteamaculans, and exhibited reduced body sizes
      and gonad lengths. We conclude that development of first-generation adults of
      both Steinernema spp. tested, in particular time to adult maturation as well as
      body and gonad size were directly influenced by the bacterial symbionts they were
      cultured with. However, response to the culture conditions was species specific.

PMID- 29458073
TI  - Establishment and validation of a prediction model for ischemic stroke risks in
      patients with type 2 diabetes.
AB  - AIMS: A risk scoring system for predicting ischemic stroke incidence may identify
      type 2 diabetes patients at high risk for ischemic stroke who can benefit from
      preventive intervention programs. Such a risk scoring system can serve as a
      benchmark to test novel putative risk factors. METHODS: The study adopted a
      retrospective cohort, including 28,124 Chinese patients with type 2 diabetes aged
      30-84 years during 2001-2004. Participants were randomly assigned to the
      derivation and validation sets at a 2:1 ratio. Cox's proportional hazard
      regression model was used to identify risk factors of ischemic stroke incidence
      in the derivation set. And then the steps proposed by the Framingham Heart Study
      for establishing an ischemic stroke prediction model with a scoring system was
      used. RESULTS: Among 9374 patients in the validation set, 1076 subjects (11.48%)
      developed ischemic stroke with a mean follow up period of 8.0 years. We
      identified the following risk factors: age, gender, smoking habit, duration of
      type 2 diabetes, blood pressure, HbA1c level, total cholesterol to high-density
      lipoprotein ratio, creatinine, fasting plasma glucose variation (FPG-CV),
      arterial embolism and thrombosis, diabetes retinopathy, hypoglycemia, anti
      diabetes medication use, and cardiovascular medication. The area under receiver
      operating characteristic curve of the 3-year, 5-year, and 8-year ischemic stroke
      incidence risks were 0.72, 0.71, and 0.68 for the validation set, respectively.
      CONCLUSIONS: This proposed ischemic stroke incidence risk prediction model is the
      first model established for Chinese patients with type 2 diabetes recruited from
      nationwide clinical settings.

PMID- 29458074
TI  - Subthalamic nucleus stimulation, dopaminergic treatment and impulsivity in
      Parkinson's disease.
AB  - BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN DBS) is known
      to increase response speed and lower response accuracy in Parkinson's disease
      (PD) patients. It has been proposed that this speed-accuracy tradeoff is due to
      enhanced sensitivity of the motor system to sensory information. An alternative
      possibility is that this effect is due to weakened suppressive processes. The two
      alternative interpretations can be tested by analyzing the electromyographic
      activity (EMG) of the response agonists when the patients perform conflict
      reaction time tasks. In those tasks, fast subthreshold muscle impulses often
      occur in the agonist of the incorrect response. These impulses are partial errors
      that are suppressed before being behaviourally committed. MATERIAL AND METHODS:
      Here we analyzed the EMG of the response agonists recorded while sixteen PD
      patients performed a Simon task that elicits prepotent response tendencies so as
      to decipher (i) whether STN DBS affects the expression and/or suppression of
      subthreshold muscle impulses that are critical for action control and (ii) the
      interaction between dopaminergic treatment and STN DBS. The patients were tested
      On and Off STN DBS and On and Off dopaminergic medication in a full factorial
      design. RESULTS: STN DBS not only impaired the proficiency to suppress subliminal
      action impulses (p = 0.01) but also favoured the muscular expression of fast
      incorrect impulses (p < 0.001). Dopaminergic treatment only affected the action
      impulses suppression (p = 0.02) and did not change the effect of STN DBS on
      impulsive action control. CONCLUSION: Contrary to a recent proposal, STN DBS
      impaired rather than improved action control by weakening erroneous impulse
      suppression, whether the patients were On or Off their usual medication. These
      findings are discussed in light of a recent proposal (Servant M, White C,
      Montagnini A, Burle B, 2015) that reconciles partial errors with accumulation-to
      bound models of decision making. Our results suggest that medication specifically
      lowers the mechanical threshold while STN DBS lowers the mechanical threshold and
      to a lesser extent the EMG-threshold.

PMID- 29458075
TI  - Lateral inhibition in the autism spectrum: An SSVEP study of visual cortical
      lateral interactions.
AB  - Circuit level brain dysfunction has been suggested as a common mechanism through
      which diverse genetic risk factors and neurobiological sequelae lead to the core
      features of autism spectrum disorder (Geschwind 2009; Port et al. 2014). An
      important mediator of circuit level brain activity is lateral inhibition, and a
      number of authors have suggested that lateral inhibition may be atypical in ASD.
      However, evidence regarding putative atypical lateral connections in ASD is
      mixed. Here we employed a steady state visual evoked potential (SSVEP) paradigm
      to further investigate lateral connections within a group of high functioning
      adults with ASD. At a group level, we found no evidence of altered lateral
      interactions in ASD. Exploratory analyses reveal that greater ASD symptom
      severity (increased ADOS score) is associated with increased short range lateral
      inhibition. These results suggest that lateral interactions are not altered in
      ASD at a group-level, but that subtle alterations in such neurobiological
      processes may underlie the heterogeneity seen in the autism spectrum in terms of
      sensory perception and behavioral phenotype.

PMID- 29458076
TI  - Bone marrow mesenchymal stem cells (BMSCs) improved functional recovery of spinal
      cord injury partly by promoting axonal regeneration.
AB  - Spinal cord injury (SCI) disrupts the spinal cord and results in the loss of
      sensory and motor function below the lesion site. The treatment of SCI became a
      challenge because the injured neurons fail to axon regenerate and repair after
      injury. Promoting axonal regeneration plays a key role in the treatment
      strategies for SCI. It would meet the goal of reconstruction the injured spinal
      cord and improving the functional recovery. Bone marrow mesenchymal stem cells
      (BMSCs) are attractive therapeutic potential cell sources for SCI, and it could
      rebuild the injured spinal cord through neuroprotection, neural regeneration and
      remyelinating. Evidence has demonstrated that BMSCs play important roles in
      mediating axon regeneration, and glial scar formation after SCI in animal
      experiments and some clinical trials. We reviewed the role of BMSCs in regulating
      axon regeneration and glial scar formation after SCI. BMSCs based therapies may
      provide a therapeutic potential for the injured spinal cord by promoting axonal
      regeneration and repair.

PMID- 29458077
TI  - Reciprocal regulation of the Cadherin-11/Stat3 axis by caveolin-1 in mouse
      fibroblasts and lung carcinoma cells.
AB  - Caveolin-1 (Cav1) is an integral plasma membrane protein and a complex regulator
      of signal transduction. The Signal Transducer and Activator of Transcription-3
      (Stat3) is activated by a number of receptor and non-receptor tyrosine kinases
      and is positively implicated in cancer. Despite extensive efforts, the
      relationship between Cav1 and Stat3 has been a matter of controversy. We
      previously demonstrated that engagement of E- or N-cadherin or cadherin-11 cell
      to cell adhesion molecules, as occurs with confluence of cultured cells, triggers
      a dramatic increase in the levels of tyr705 phosphorylated i.e. activated Stat3,
      by a mechanism requiring the cRac1 small GTPase. Since confluence was not taken
      into account in previous studies, we revisited the question of the relationship
      between Cav1 and Stat3-ptyr705 in non-transformed mouse fibroblasts and in human
      lung carcinoma cells, by examining their effect at different cell densities. Our
      results unequivocally demonstrate that Cav1 downregulates cadherin-11, by a
      mechanism which requires the Cav1 scaffolding domain. This cadherin-11
      downregulation, in turn, leads to a reduction in cRac1 and Stat3 activity levels.
      Furthermore, in a feedback loop possibly through p53 upregulation, Stat3
      downregulation increases Cav1 levels. Our data reveal the presence of a potent,
      negative regulatory loop between Cav1 and cadherin-11/Stat3, leading to Stat3
      inhibition and apoptosis.

PMID- 29458078
TI  - Isolation of intact RNA from murine CD4+ T cells after intracellular cytokine
      staining and fluorescence-activated cell sorting.
AB  - Intracellular cytokine staining (ICS) is a powerful method for identifying
      functionally distinct lymphocyte subsets, and for isolating these by fluorescence
      activated cell sorting (FACS). Although transcriptomic analysis of cells sorted
      on the basis of ICS has many potential applications, this is rarely performed
      because of the difficulty in isolating intact RNA from cells processed using
      standard fixation and permeabilization buffers for ICS. To address this issue, we
      compared three buffers shown previously to preserve RNA in nonhematopoietic cells
      subjected to intracellular staining for their effects on RNA isolated from T
      lymphocytes processed for ICS. Our results showed that buffers containing the
      recombinant ribonuclease inhibitor RNasin or high molar concentrations of salt
      yielded intact RNA from fixed and permeabilized T cells. As proof of principle,
      we successfully used the buffer containing RNasin to isolate intact RNA from CD4+
      T cells that were sorted by FACS on the basis of specific cytokine production,
      thus demonstrating the potential of this approach for coupling ICS with
      transcriptomic analysis.

PMID- 29458079
TI  - Autofluorescence: A potential pitfall in immunofluorescence-based inflammation
      grading.
AB  - Immunofluorescence (IF) staining of paraffin-embedded tissues is a frequently
      used method to answer research questions or even detect the abundance of a
      certain protein for diagnostic use. However, the signal originating from specific
      antibody-staining might be distorted by autofluorescence (AF) of the assessed
      tissue. Although the AF phenomenon is well known, its presence is often neglected
      by insufficient staining controls. In this study, we describe the existence of
      cellular AF in paraffin-embedded healthy and inflamed human and murine colonic
      tissues and present ways to reduce AF. The AF signal is detectable at emission
      spectra from 425 nm-738 nm, upon excitation from 403.6-638.7 nm and appears more
      pronounced in inflamed tissues. Most signals are located subepithelially in the
      tissue and in blood vessels. Previous studies have shown that the AF signals are
      caused by lipofuscin, which accumulates in lamina propria immune cells. In murine
      small intestine AF signals are present in granules in the Paneth cell zone. For
      alleviation of the AF signal, sudan black b (SBB) or copper sulfate was used.
      Incubation of the tissue slices with either one of the substances reduced AF. In
      conclusion, AF appears as an intrinsic biomarker for colonic inflammation. The
      dominant existence of AF in immune cells of IBD tissue elucidates the importance
      of negative controls and the limitation of IF staining for potential diagnostic
      purposes.

PMID- 29458081
TI  - Di (2-ethylhexyl) phthalate (DEHP) alters proliferation and uterine gland numbers
      in the uteri of adult exposed mice.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) is an endocrine-disrupting chemical that has
      been shown to impair normal reproductive function in males and females. This
      study investigated whether adult exposure to environmental and occupational doses
      of DEHP alters homeostasis of uterine proliferation, morphology, and number of
      uterine glands. Adult female CD1 mice were orally dosed with DEHP (0, 20
      MUg/kg/day, 200 MUg/kg/day, 20 mg/kg/day or 200 mg/kg/day) for 30 days. Results
      indicated that DEHP at 200 MUg/kg/day caused a reduction in epithelial cell
      proliferation in the uterus (p < .05). We also observed an increase (p < .05) in
      the number of uterine glands in mice dosed with 200 mg/kg/day DEHP. Results
      showed that DEHP caused an increase (p < .05) in dilated blood vessels in the
      endometrium at 200 MUg/kg/day, 20 mg/kg/day and 200 mg/kg/day. DEHP also
      increased proliferation of endometrial stromal cells at 200 MUg/kg/day DEHP (p <
      .0010), 20 mg/kg/day DEHP (p < .0001) and 200 mg/kg/day DEHP (p < .0186). Results
      suggest that, exposure to specific doses of DEHP for 30 days can have adverse
      effects on reproductive function.

PMID- 29458080
TI  - Transcriptomic and phenotypic profiling in developing zebrafish exposed to
      thyroid hormone receptor agonists.
AB  - There continues to be a need to develop in vivo high-throughput screening (HTS)
      and computational methods to screen chemicals for interaction with the estrogen,
      androgen, and thyroid pathways and as complements to in vitro HTS assays. This
      study explored the utility of an embryonic zebrafish HTS approach to identify and
      classify endocrine bioactivity using phenotypically-anchored transcriptome
      profiling. Transcriptome analysis was conducted on zebrafish embryos exposed to
      25 estrogen-, androgen-, or thyroid-active chemicals at concentrations that
      elicited adverse malformations or mortality at 120 h post-fertilization in 80% of
      animals exposed. Analysis of the top 1000 significant differentially expressed
      transcripts and developmental toxicity profiles across all treatments identified
      a unique transcriptional and phenotypic signature for thyroid hormone receptor
      agonists. This unique signature has the potential to be used as a tiered in vivo
      HTS and may aid in identifying chemicals that interact with the thyroid hormone
      receptor.

PMID- 29458082
TI  - Beyond Pain: Nurses' Assessment of Patient Suffering, Dignity, and Dying in the
      Intensive Care Unit.
AB  - CONTEXT: Deaths in the intensive care unit (ICU) are increasingly common in the
      U.S., yet little is known about patients' experiences at the end of life in the
      ICU. OBJECTIVES: The objective of this study was to determine nurse assessment of
      symptoms experienced, and care received by ICU patients in their final week, and
      their associations with nurse-perceived suffering and dignity. METHODS: From
      September 2015 to March 2017, nurses who cared for 200 ICU patients who died were
      interviewed about physical and psychosocial dimensions of patients' experiences.
      Medical chart abstraction was used to document baseline patient characteristics
      and care. RESULTS: The patient sample was 61% males, 70.2% whites, and on average
      66.9 (SD 15.1) years old. Nurses reported that 40.9% of patients suffered
      severely and 33.1% experienced severe loss of dignity. The most common symptoms
      perceived to contribute to suffering and loss of dignity included trouble
      breathing (44.0%), edema (41.9%), and loss of control of limbs (36.1%). Most (n =
      9) remained significantly (P < 0.05) associated with suffering, after adjusting
      for physical pain, including fever/chills, fatigue, and edema. Most patients
      received vasopressors and mechanical ventilation. Renal replacement therapy was
      significantly (<0.05) associated with severe suffering (adjusted odds ratio [AOR]
      2.53) and loss of dignity (AOR 3.15). Use of feeding tube was associated with
      severe loss of dignity (AOR 3.12). CONCLUSION: Dying ICU patients are perceived
      by nurses to experience extreme indignities and suffer beyond physical pain.
      Attention to symptoms such as dyspnea and edema may improve the quality of death
      in the ICU.

PMID- 29458084
TI  - WITHDRAWN: Severe Pulmonary Embolism Secondary to Cement Embolism in the Inferior
      Vena Cava after Percutaneous Vertebroplasty.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      https://doi.org/10.1016/j.avsg.2018.01.003. The duplicate article has therefore
      been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 29458083
TI  - Endovascular Treatment of Isolated Degenerative Superficial Femoral Artery
      Aneurysm.
AB  - Isolated degenerative superficial femoral artery (SFA) aneurysms are rare. One
      hundred forty-two cases are described in literature. Threshold for operative
      management varies in literature. In literature, only 10 cases are treated in an
      endovascular way. We present a case of a 77-year-old patient who presented with
      nonhealing wounds on the right foot. Duplex ultrasound revealed an isolated
      aneurysm of the SFA on the right side as a source of emboli. The patient was
      treated in an endovascular way with a covered stent graft. The procedure was
      complicated by embolization in the peroneal artery as a single outflow vessel. An
      overview of endovascular treatment of SFA aneurysms in literature is discussed.

PMID- 29458085
TI  - The effect of surface charge and pH on the physiological behaviour of cobalt,
      copper, manganese, antimony, zinc and titanium oxide nanoparticles in vitro.
AB  - The precise knowledge on various interactions of metal nanoparticles (NP) in a
      living organism is scarce. It is expected that metals can bind to nucleic acids,
      peptides and proteins (e.g. enzymes), and modify the functioning of vital
      cellular compartments after entering the organism. The predictive factors for
      quantitative nanostructure-activity relationship (QNAR) analysis could enhance
      efficient and harmless usage of nanoparticles (NPs) in the industry as well in
      the medicine. The studies value the composition of the NP corona determined by
      time, temperature and source of protein which has been found to implicate the
      physiological behaviour of NPs. One has largely been ignored: the NPs specific
      isoelectric point (IEP) and pH at the state of measurement. Herein, this study
      investigates the effect of pH and surface charge of six metal oxide (MeOx) NPs on
      time dependency of cytotoxicity. Several aspects of the characterization of
      ultrafine particles in the actual test system which is the most relevant for the
      interpretation of the toxicological data are referred: (i) the difference of pH
      in the room temperature and in the incubation conditions (ii) the difference of
      dispersions in MilliQ and complete cell media; (iii) the need to exemplify also
      the pH and isoelectric point when the hydrodynamic size is measured; (iv) the
      importance of time due to the time-dependent equilibration and changes of NPs
      corona. The surface charge determines the formation of corona and could be
      modified by pH. MeOx NPs without fully charge equilibrated corona might play the
      main role of MeOx NPs entering into the cell and consequently the time dependent
      manifestation of the cellular effect.

PMID- 29458086
TI  - Characterization of uniaxial high-speed stretch as an in vitro model of mild
      traumatic brain injury on the blood-brain barrier.
AB  - Traumatic brain injury (TBI) occurs when external mechanical forces induce brain
      damage as result of impact, penetration or rapid acceleration/deceleration that
      causes deformation of brain tissue. Depending on its severity, TBI can be
      classified as mild, moderate or severe and can lead to blood-brain barrier (BBB)
      dysfunction. In the present study, we evaluated the effects of uniaxial high
      speed stretch (HSS) at 0, 5, 10 and 15% on a pure culture of primary rat brain
      endothelial cells as an in vitro model of TBI to the BBB. LDH release, viability
      and apoptosis analysis, expression of tight junction proteins and endothelial
      permeability were evaluated 24 h after a single stretch episode. HSS slightly
      increased cell death and apoptosis at 10 and 15%, while LDH release was increased
      only at 15% stretch. Occludin expression was increased at 10% stretch, while
      claudin-5 expression was increased at 5% stretch, which also decreased the
      endothelial permeability. In summary, 15% HSS induced low levels of cell death,
      consistent with mild TBI and very low percentages of HSS (5%) enhanced the BBB
      properties, promoting the formation of a stronger barrier. These data support the
      use of 15% HSS as valuable tool in the study of mild TBI to the BBB in vitro.

PMID- 29458087
TI  - NGF/FAK signal pathway is implicated in angiogenesis after acute cerebral
      ischemia in rats.
AB  - Neurogenesis in the cerebral infarction after an ischemic event is important to
      the rehabilitation of patients. However, the mechanism of angiogenesis around
      cerebral ischemia is not clear. Our study designed to test whether the nerve
      growth factor (NGF)-P-focal adhesion kinase (FAK) signaling pathway for
      associations with angiogenesis plays a key role in post-acute cerebral ischemia
      of rats. Firstly, we implanted the Matrigel, a carrier of basement membrane
      matrix, into the abdominal skin of rats to identify the relevant components of
      the NGF-P-FAK signaling pathway related to angiogenesis. Secondly, we used a
      model established by ligation of the middle cerebral artery (MCA) to observe the
      effect of the same signal pathway on angiogenesis in the subventricular and
      subgranular zones of the dentate gyrus(SVG and SGZ). The results showed that the
      tissue scores was significantly increased by NGF. However, the tissue scores was
      signifcaintly decreased by FAK inhibitor TAE226. Furthermore, CD31 and alpha-SMA
      were significantly increased by NGF and were decreased by anti-NGF and TAE226 in
      Matrigel. The P-FAK protein expression in Matrigel was markedly increased by NGF
      and decreased by TAE226. In the SVZ and SVG of cerebral ischemia, the numbers of
      BrdU-positive cells were significantly increased by NGF and decreased by TAE226,
      respectively. Our findings suggest that the therapy targeting the NGF-P-FAK
      signaling pathway may be an option for patients suffering from cerebral ischemia.

PMID- 29458088
TI  - Antibiotics use among Palestine refugees attending UNRWA primary health care
      centers in Jordan - A cross-sectional study.
AB  - : The irrational use of antibiotics is increasing in Jordanian refugee camps and
      consequently so too is bacterial resistance. About one-third of health
      expenditures at UNRWA health centers in Jordan are attributed to antibiotics.
      OBJECTIVE: We studied knowledge, attitude and behaviour of Palestine refugees
      attending UNRWA health centers in Jordan regarding antibiotic use in order to
      plan public health interventions accordingly. METHODS: A cross-sectional,
      interviewer-administered survey among 250 adult Palestine refugees at four
      different health centers was conducted. RESULTS: Irrational antibiotic use was
      widespread: 63% of patients share antibiotics at home, 38% use left-over
      antibiotics and 60% purchase antibiotics directly from the pharmacy without
      prescription (OTC) .1 At the same time, knowledge about antibiotics side effects,
      resistance, and target agent was low. 90% of patients trust their doctor, however
      long waiting hours prevent them from seeking medical advice, which significantly
      increased self-medication. CONCLUSIONS: Our findings suggest a strong need for
      public education about antibiotics. In addition, health institutional level
      improvements such as shorter waiting hours and strict regulations prohibiting
      dispensing without prescription are necessary to combat growing bacterial
      resistance.

PMID- 29458089
TI  - Structural and biophysical insight into dual site binding of the protoberberine
      alkaloid palmatine to parallel G-quadruplex DNA using NMR, fluorescence and
      Circular Dichroism spectroscopy.
AB  - Plant derived small molecules, which interact with and stabilize G-quadruplex
      DNA, act as inhibitors of telomere elongation and oncogene expression in humans.
      The inhibition of telomerase enzyme has immense potential since it is over
      expressed in most cancer cells. Interaction of palmatine, an antitumor alkaloid,
      to parallel G-quadruplex DNA, [d(TTGGGGT)]4 and [d(TTAGGGT)]4, has been
      investigated using Nuclear Magnetic Resonance (NMR), fluorescence and Circular
      Dichroism (CD) spectroscopy. Titrations were monitored by 1H and 31P NMR spectra
      and solution structure of palmatine-[d(TTGGGGT)]4 complex was obtained by
      restrained Molecular Dynamics (rMD) simulations using distance restraints from 2D
      NOESY spectra. Thermal stabilization of DNA was determined by CD, 1H NMR and
      Differential Scanning Calorimetry (DSC). Binding of palmatine induces 98%
      enhancement of fluorescence accompanied by blue shift ~8 nm. CD spectral bands of
      DNA show minor changes. Diffusion NMR studies confirm formation of a stable
      complex. Proton NMR signals of palmatine shift upfield upon binding and NOE cross
      peaks of H10, H3, H28, 5OCH3 protons with T2, A3/G3, G6 and T7 residues reveal
      dual recognition sites in both G-quadruplex DNA sequences, resulting in thermal
      stabilization of G-quadruplex by ~13-17  degrees C. Restrained molecular dynamics
      simulations using NOE distance restraints for 2:1 palmatine-[d(TTGGGGT)]4 complex
      reveal end-stacking of palmatine at G6pT7 step and groove binding along T2pG3
      step. Binding to [d(TTAGGGT)]4 takes place at T2pA3pG4 and G6pT7 steps.
      Structural features of molecular recognition of two different G-quadruplex DNA
      sequences by palmatine have relevance in rational drug development for anti
      cancer therapy.

PMID- 29458090
TI  - Designing fluorescent biosensors using circular permutations of riboswitches.
AB  - RNA-based fluorescent (RBF) biosensors have been applied to detect a variety of
      metabolites in vitro and in live cells. They are designed by combining the ligand
      sensing domain of natural riboswitches with in vitro selected fluorogenic
      aptamers. Different biosensor topologies have been developed to accommodate the
      diversity of riboswitch structures. Here we show that circular permutation of the
      riboswitch ligand sensing domain also gives functional biosensors, using the SAM
      I riboswitch as our model. We reveal that this design can enhance fluorescence
      turn-on and ligand binding affinity compared to the non-permuted topology.

PMID- 29458092
TI  - Ramifications of the Children's Surgery Verification Program for Patients and
      Hospitals.
AB  - BACKGROUND: The American College of Surgeons in 2015 instituted the Children's
      Surgery Verification program delineating requirements for hospitals providing
      pediatric surgical care. Our purpose was to examine possible effects of the
      Children's Surgery Verification program by evaluating neonates undergoing high
      risk operations. STUDY DESIGN: Using the Kid's Inpatient Database 2009, we
      identified infants undergoing operations for 5 high-risk neonatal conditions. We
      considered all children's hospitals and children's units Level I centers and
      considered all others Level II/III. We estimated the number of neonates requiring
      relocation and the additional distance traveled. We used propensity score
      adjusted logistic regression to model mortality at Level I vs Level II/III
      hospitals. RESULTS: Overall, 7,938 neonates were identified across 21 states at
      91 Level I and 459 Level II/III hospitals. Based on our classifications, 2,744
      (34.6%) patients would need to relocate to Level I centers. The median additional
      distance traveled was 6.6 miles. The maximum distance traveled varied by state,
      from <55 miles (New Jersey and Rhode Island) to >200 miles (Montana, Oregon,
      Colorado, and California). The adjusted odds of mortality at Level II/III vs
      Level I centers was 1.67 (95% CI 1.44 to 1.93). We estimate 1 life would be saved
      for every 32 neonates moved. CONCLUSIONS: Although this conservative estimate
      demonstrates that more than one-third of complex surgical neonates in 2009 would
      have needed to relocate under the Children's Surgery Verification program, the
      additional distance traveled is relatively short for most but not all, and this
      program might improve mortality. Local level ramifications of this novel national
      program require additional investigation.

PMID- 29458091
TI  - Role of the sseK1 gene in the pathogenicity of Salmonella enterica serovar
      enteritidis in vitro and in vivo.
AB  - Salmonella enteritidis is a common food-borne pathogen associated with
      consumption of contaminated poultry meat and eggs, which frequently causes
      gastroenteritis in humans. Salmonella secreted effector K1 (SseK1), as a
      translocated and secreted protein has been identified to be essential for the
      virulence of Salmonella typhimurium in host cells. However, the role of the sseK1
      gene in the pathogenicity of S. enteritidis remain unclear. In this study, a
      sseK1 deletion mutant of S. enteritidis was constructed and its biological
      characteristics were examined. It was found that the sseK1 deletion mutant did
      not affect the growth, adherence and invasion of Salmonella enteritidis when
      compared to the wild-type S. enteritidis. However, the mutant showed decreased
      formation of biofilm and significantly reduced intracellular survival of bacteria
      in activated mouse peritoneal macrophages, as well as showed reduced
      pathogenicity to a murine model by increasing the lethal dose 50% (LD50) value
      and decreasing the proliferation ratio of bacteria in vivo. Taken together, this
      study determined an important role for SseK1 in the pathogenicity of S.
      enteritidis in vitro and in vivo.

PMID- 29458093
TI  - Protective efficacy of Mucuna pruriens (L.) seed meal enriched diet on growth
      performance, innate immunity, and disease resistance in Oreochromis mossambicus
      against Aeromonas hydrophila.
AB  - The impact of Mucuna pruriens (L.) seed meal diet on growth performance, innate
      immune response, and disease resistance in Oreochromis mossambicus against
      Aeromonas hydrophila is reported for the first time. Infected O. mossambicus was
      fed with 2 g kg-1, 4 g kg-1, and 6 g kg-1 of M. pruriens seed meal diets
      significantly increased initial body weight (IBW) and final body weight (FBW)
      over control, for a period of 4 weeks. At 4 g kg-1 and 6 g kg-1 the enriched diet
      significantly (P < 0.05) enhanced the survival rate, weight gain (WG), protein
      efficiency ratio (PER), specific growth rate (SGR), feed conversion ratio (FCR),
      and feed efficiency (FE) when compared to the control; besides, from weeks 2-4
      these diets significantly (P < 0.05) enhanced the complement activity, phagocytic
      activity, respiratory burst activity, and lysosome activity. On being fed with 4
      g kg-1 and 6 g kg-1-enriched diets the cumulative mortality was lower (10% and
      12%) than with 2 g kg-1 diet (24%). The present investigation suggests that the
      enriched diet at 4 g kg-1 and 6 g kg-1 improved the growth performance more than
      that of the control and negative control; it also positively enhanced the innate
      immunity and disease resistance against A. hydrophilla in O. mossambicus. Hence
      M. pruriens can be used as a feed additive to stimulate immunity for effective
      production of economically valuable freshwater fish, O. mossambicus.

PMID- 29458094
TI  - A conserved interferon regulation factor 1 (IRF-1) from Pacific oyster
      Crassostrea gigas functioned as an activator of IFN pathway.
AB  - Interferon regulatory factors (IRFs), a family of transcription factors with a
      novel helix-turn-helix DNA-binding motif, play important roles in regulating the
      expression of interferons (IFNs) and IFN-stimulated genes. In the present study,
      an interferon regulation factor 1 was identified from oyster Crassostrea gigas
      (designated CgIRF-1), and its immune function was characterized to understand the
      regulatory mechanism of interferon system against viral infection in
      invertebrates. The open reading frame (ORF) of CgIRF-1 was 990 bp, encoding a
      polypeptide of 329 amino acids with a typical IRF domain (also known as DNA
      binding domain). The mRNA transcripts of CgIRF-1 were detected in all the tested
      tissues with the highest expression level in hemocyte. CgIRF-1 protein was
      distributed in both nucleus and cytoplasm of the oyster hemocyte. The mRNA
      expression of CgIRF-1 in hemocytes was significantly up-regulated at 48 h after
      poly (I:C) stimulation (p < 0.05). The recombinant CgIRF-1 (rCgIRF-1) could
      interact with classically IFN-stimulated response elements (ISRE) in vitro. The
      relative luciferase activity of interferon-like protein promotor reporter gene
      (pGL-CgIFNLP promotor) was significantly (p < 0.05) enhanced in HEK293T cell
      after transfection of CgIRF-1. These results indicated that CgIRF-1 could bind
      ISRE and regulate the expression of CgIFNLP as a transcriptional regulatory
      factor, and participated in the antiviral immune response of oysters.

PMID- 29458095
TI  - Rapid, Loop-Mediated Isothermal Amplification Detection of Celiac Disease Risk
      Alleles.
AB  - Human leukocyte antigen (HLA) genotyping has become a useful investigation in the
      diagnostic work-up of celiac disease (CD), with utility in risk stratification
      and screening. However, broad application of this technology has been hindered by
      the cost and time burden of conventional laboratory-based assays. We have
      developed and validated CD-loop-mediated isothermal amplification (CD-LAMP), a
      LAMP assay, which enables rapid identification of the signature CD risk
      genotypes, HLA-DQ2.5, HLA-DQ8, HLA-DQ2.2, and HLA-DQA1*05. Sample-to-answer is
      achieved in approximately 65 minutes without DNA purification, thermal cycling,
      or specialized analytical equipment. CD-LAMP genotyping of samples was 100%
      concordant with accredited pathology genotyping on a panel of 40 blood and 20
      saliva samples. In a panel of 100 purified DNA samples, genotyping of the high
      risk DQ2.5 genotype was 100% concordant with accredited pathology genotyping,
      with slightly reduced sensitivity for the DQ8 genotype (97.1%) and reduced
      specificity for the DQ8 (93.9%) and DQ2.2 (95.1%) genotypes. CD-LAMP results are
      easily visualized and instrument free through the addition of a DNA intercalating
      dye after amplification. Combined with point-of-care antibody testing, CD-LAMP
      may enable immediate, confident CD diagnosis at a low cost in the clinical
      setting.

PMID- 29458096
TI  - Identification of macrophage-related candidate genes in lupus nephritis using
      bioinformatics analysis.
AB  - Lupus nephritis (LN) is a chronic autoimmune disorder. Here we try to identify
      the candidate genes in macrophages related to LN. We performed a systematic
      search in the Gene Expression Omnibus (GEO) database for microarray in human
      mononuclear cells and mouse macrophages of LN. The results of clustering and venn
      analysis of different GEO datasets showed that 8 genes were up-regulated and 2
      genes down-regulated in samples from both human and mouse LN. The data from gene
      network and GO analysis revealed that CD38 and CCL2 were localized in the core of
      the network. Immunofluorescence staining showed that CD38 expression was markedly
      increased in macrophages from kidneys with LN. Our study identifies the gene
      expression profile for macrophages and demonstrated the induction of CCL2 and
      CD38 in macrophages from patients with LN. However, regarding the limited patient
      number included in this study, the results are preliminary and more studies are
      still needed to further decipher the macrophage-related candidate genes for the
      pathogenesis of LN.

PMID- 29458097
TI  - Topographical memory analyzed in mice using the Hamlet test, a novel complex
      maze.
AB  - The Hamlet test is an innovative device providing a complex environment for
      testing topographic memory in mice. Animals were trained in groups for weeks in a
      small village with a central agora, streets expanding from it towards five
      functionalized houses, where they can drink, eat, hide, run, interact with a
      stranger mouse. Memory was tested by depriving mice from water or food and
      analyzing their ability to locate the Drink/Eat house. Exploration and memory
      were analyzed in different strains, gender, and after different training periods
      and delays. After 2 weeks training, differences in exploration patterns were
      observed between strains, but not gender. Neuroanatomical structures activated by
      training, identified using FosB/DeltaFosB immunolabelling, showed an involvement
      of the hippocampus-subiculum-parahippocampal gyrus axis and dopaminergic
      structures. Training increased hippocampal neurogenesis (cell proliferation and
      neuronal maturation) and modified the amnesic efficacy of muscarinic or nicotinic
      cholinergic antagonists. Moreover, topographical disorientation in Alzheimer's
      disease was addressed using intracerebroventricular injection of amyloid beta25
      35 peptide in trained mice. When retested after 7 days, Abeta25-35-treated mice
      showed memory impairment. The Hamlet test specifically allows analysis of
      topographical memory in mice, based on complex environment. It offers an
      innovative tool for various ethological or pharmacological research needs. For
      instance, it allowed to examine topographical disorientation, a warning sign in
      Alzheimer's disease.

PMID- 29458098
TI  - Spermine protects from LPS-induced memory deficit via BDNF and TrkB activation.
AB  - Lipopolysaccharide (LPS) has been long known to promote neuroinflammation and
      learning and memory deficits. Since spermine, one of the main natural polyamines
      in the central nervous system, protects from LPS-induced memory deficit by a
      mechanism that comprises GluN2B receptors, the aim of the present study was to
      determine whether brain-derived neurotrophic factor (BDNF), tropomyosin-related
      kinase B (TrkB) receptor and cAMP response element binding (CREB) are involved in
      this protective effect of spermine. Adult male Swiss albino mice received,
      immediately after training in the novel object recognition task, saline or LPS
      (250 MUg/kg, i.p.); 5 min later they received saline or spermine (0.3 mg/kg,
      i.p.) and, when specified, 5 min thereafter saline or the TrkB receptor
      antagonist ANA-12 (0.5 mg/kg, i.p.) in different flanks. Animals were tested 24 h
      after training. Spermine protected from LPS-induced memory deficit and this
      protective effect was reversed by ANA-12. In a subset of animals BDNF, CREB and
      phospho-CREB immunoreactivity was determined in the hippocampi and cerebral
      cortex 4 h after spermine injection. Spermine reversed the decrease of mature
      BDNF levels induced by LPS in both hippocampus and cerebral cortex. Spermine
      increased phospho-CREB content and phospho-CREB/total CREB ratio in the cerebral
      cortex of LPS-treated mice. The results support that the protective effect of
      spermine on LPS-induced memory deficits depends on TrkB receptor activation and
      is accompanied by restoration of mature BDNF levels in hippocampus and cerebral
      cortex, as well as increased CREB phosphorylation in the cerebral cortex.

PMID- 29458099
TI  - Using near infrared spectroscopy to predict the lignin content and monosaccharide
      compositions of Pinus radiata wood cell walls.
AB  - Near infrared (NIR) spectroscopy coupled with partial least squares (PLS-1)
      regression was used to predict the lignin contents and monosaccharide
      compositions of milled wood of Pinus radiata. The effects of particle size and
      moisture content were investigated by collecting NIR spectra of four sample
      types: large (<0.422mm) and small (<0.178mm) particles, in both ambient and dry
      conditions. PLS-1 models were constructed using mixtures of compression wood (CW)
      and opposite wood (OW) that provided a linear range of cell-wall compositions.
      Our results show that lignin contents and monosaccharide compositions of pure CWs
      and OWs can be successfully predicted using NIR spectra of all four sample types.
      However, large particles in ambient conditions have the most efficient
      preparation and the standard error (SE) values for lignin (2.10%), arabinose
      (0.34%), xylose (1.33%), galactose (2.54%), glucose (6.98%), mannose (1.48%),
      galacturonic acid (0.22%), glucuronic acid (0.06%), and 4-O-methylglucuronic acid
      (0.25%) were achieved.

PMID- 29458100
TI  - Characterization and antioxidant activities of polysaccharides from thirteen
      boletus mushrooms.
AB  - Water-soluble polysaccharides were extracted from the caps and stipes of thirteen
      boletus mushrooms representing five different species collected in Southwest
      China. Investigations of their structures and antioxidant activities allowed an
      evaluation of structure-function relationships. The polysaccharides were composed
      mainly of the monosaccharides arabinose, xylose, mannose, glucose and galactose.
      Most samples displayed a broad molecular weight range, with significant
      differences observed between the molecular weight ranges of the polysaccharides
      from the caps and the stipes. FT-IR spectral analysis of the polysaccharides
      revealed that most of polysaccharides from boletus mushrooms (except Boletus
      edulis) contained a pyranose ring. The antioxidant activities of the
      polysaccharides in stipes showed a significant correlation with their
      monosaccharide composition, and were also related to their molecular weight and
      anomeric configuration. Suillellus luridus collected in Pingwu, Mianyang,
      Sichuan, China had remarkably superior antioxidant activity and might be
      developed as a natural antioxidant.

PMID- 29458101
TI  - Optimization of pectinase immobilization on grafted alginate-agar gel beads by 24
      full factorial CCD and thermodynamic profiling for evaluating of operational
      covalent immobilization.
AB  - Pectinase produced by a honey derived from the fungus Aspergillus awamori
      KX943614 was covalently immobilized onto gel beads made of alginate and agar.
      Polyethyleneimine, glutaraldehyde, loading time and enzyme's units were optimized
      by 24 full factorial central composite design (CCD). The immobilization process
      increased the optimal working pH for the free pectinase from 5 to a broader range
      of pH4.5-5.5 and the optimum operational temperature from 55 degrees C to a
      higher temperature, of 60 degrees C, which is favored to reduce the enzyme's
      microbial contamination. The thermodynamics studies showed a thermal stability
      enhancement against high temperature for the immobilized formula. Moreover, an
      increase in half-lives and D-values was achieved. The thermodynamic studies
      proved that immobilization of pectinase made a remarkable increase in enthalpy
      and free energy because of enzyme stability enhancement. The reusability test
      revealed that 60% of pectinase's original activity was retained after 8
      successive cycles. This gel formula may be convenient for immobilization of other
      industrial enzymes.

PMID- 29458102
TI  - gamma-Irradiated chitosan based injectable hydrogels for controlled release of
      drug (Montelukast sodium).
AB  - Novel pH-sensitive gamma-irradiated low molecular weight (MW) chitosan (CS) (pre
      irradiated) and poly (vinyl alcohol) (PVA) blended injectable hydrogels,
      crosslinked with varying concentrations of glycerol, were fabricated for drug
      delivery application. The effect of low MW irradiated CS on controlled drug
      release was evaluated to address the problem of higher viscosity and lower
      solubility of high MW CS. The FTIR spectra of hydrogels depicted the presence of
      all the incorporated functional groups and the developed interactions (physical
      and chemical). The surface morphology of hydrogels assessed by scanning electron
      microscope exhibited porous microstructure. All hydrogels were subjected to the
      swelling analysis in different media (water, buffer and electrolytes). The pH
      sensitive hydrogel samples exhibited less swelling at acidic and neutral pH while
      higher swelling at basic pH. CPG-0.5 showed the highest swelling at all pH media
      as compared to other hydrogel samples. CPG-1.0 was selected for the release
      analysis of drug because of its highest swelling (114.47%) in distilled water
      having neutral pH. It was loaded with model drug (Montelukast Sodium) during the
      preparation phase and studied for drug release capability. The in-vitro
      controlled release evaluation of hydrogel (CPG-1.0) was performed in SGF and SIF
      using UV-visible spectroscopy. The results confirmed their applications in
      injectable drug release systems as all the loaded drug was released in 30 min in
      SGF (pH -1.2) while the release of drug in SIF (pH -6.8) was in controlled manner
      (99.62% in 3 h). The improved antibacterial activity of these hydrogel films was
      owing to the fact that the gamma-irradiated low MW CS has ruptured the bacterial
      cell and its metabolism more efficiently by inflowing in the cell.

PMID- 29458103
TI  - Zinc oxide nanorod clusters deposited seaweed cellulose sheet for antimicrobial
      activity.
AB  - Seaweed cellulose was isolated from green seaweed Ulva fasciata using a common
      bleaching agent. Sheet containing porous mesh was prepared from the extracted
      seaweed crystalline cellulose along with zinc oxide (ZnO) nanorod clusters grown
      over the sheet by single step hydrothermal method. Seaweed cellulose and zinc
      oxide nanorod clusters deposited seaweed cellulose sheet was characterized by FT
      IR, XRD, TGA, and SEM-EDX. Morphology showed that the diameter of zinc oxide
      nanorods were around 70nm. Zinc oxide nanorod clusters deposited on seaweed
      cellulose sheet gave remarkable antibacterial activity towards gram-positive
      (Staphylococcus aureus, Bacillus ceresus, Streptococcus thermophilis) and gram
      negative (Escherichia coli, Pseudomonas aeruginous) microbes. Such deposited
      sheet has potential applications in pharmaceutical, biomedical, food packaging,
      water treatment and biotechnological industries.

PMID- 29458104
TI  - A new l-glutaminase from Streptomyces pratensis NRC 10: Gene identification,
      enzyme purification, and characterization.
AB  - In the current study, the purified l-glutaminase from Streptomyces pratensis
      NRC10 (GenBank number KC857622) was characterized. Its molecular weight was
      estimated to be 46kDa and isoelectric point 7.4. Its Vmax was calculated to be
      2.19U/mg/min, while Km was 0.175mM. The optimum pH and temperature were 9 and 45
      degrees C, respectively. It was thermostable at 45 degrees C but thermally
      inactivated at 60 degrees C after 50min. Moreover, its enzymatic activity was
      enhanced by K+ ions and inhibited by Mg2+, Cu2+, Ag+, Hg2+, Ni2+, Fe2+, Cr2, Na+,
      Ca2+, and EDTA. A PCR fragment of 1550bp of S. pratensis NRC10 l-glutaminase gene
      (glsA) was purified and its sequence was determined (GenBank number KJ567136). l
      glutaminase from NRC10 was induced mainly by l-glutamic acid. Model 3-D structure
      was composed of two domains, the serine - dependent beta-lactamase dominant the
      small STAS domain (Sulphate Transporter and anti-sigma factor antagonist) which
      had probably functioned as a general NTP binding domain. The two domains are
      linked by a linker peptide (GLHLMRNPALPGST), but sequence alignment between salt
      tolerant glutaminase and the obtained glutaminase showed 44.75% of identity and
      57% of similarity. This enzyme appears to have a distinctive structure compared
      to the rest of glutaminase family, and seems to construct a new subgroup of
      glutaminase.

PMID- 29458105
TI  - Preparation and characterization of antibacterial, eco-friendly edible
      nanocomposite films containing Salvia macrosiphon and nanoclay.
AB  - Nowadays, food security is a vital issue and antimicrobial packaging could play
      an important role in this matter. In this regard, Salvia macrosiphon seed
      mucilage (SSM) and nanoclay, as new sources for the production of food-grade
      edible films were investigated. These edible films were prepared by incorporation
      of SSM with glycerol and different percentage of nanoclay. Upon addition of
      nanoclay up to 2% physical, mechanical and thermal properties were considerably
      improved and the composite films showed the lowest water vapor permeability
      (WVP), as well as highest elongation at break and tensile strength. The
      nanocomposite edible films also showed antibacterial activity due to the SSM
      nature. Addition of nanoclay, increased the hydrophobicity, which makes the films
      great alternatives for food packaging. This study revealed that these novel
      antimicrobial edible films could be a promising packaging option for a wide range
      of food products.

PMID- 29458106
TI  - Combi-metal organic framework (Combi-MOF) of alpha-amylase and glucoamylase for
      one pot starch hydrolysis.
AB  - The multi-enzyme biocatalyst allows to run in vitro multi-step cascade reactions
      in single pot. An efficient combi-metal organic frameworks (combi-MOF) of alpha
      amylase and glucoamylase for one pot starch hydrolysis was constructed by mixing
      zinc acetate and 2-methylimmidazole with enzyme mixture in one pot under
      biocompatible conditions. The prepared combi-MOF was characterized and analyzed
      by powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR),
      thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). Thermo
      stability was evaluated for combi-MOF in the range of 55 to 75 degrees C which
      showed three folds improved stability in terms of half-life. In kinetic parameter
      studies, rate of starch hydrolysis (Vmax) of combi-MOF was found to be enhanced
      after co-immobilization. Further, combi-MOF was recycled in batch mode which
      retained up to 52% residual activity after five successive cycles of reuse. In
      addition to that, combi-MOF exhibited extraordinary storage stability till
      24days. At the end, starch hydrolytic activity of combi-MOF was tested for
      different sources of starch (corn, rice, wheat and potato) which exhibited higher
      rate of hydrolysis than mixture of free enzymes due to spatially co-localized
      multi-enzymatic systems.

PMID- 29458107
TI  - WNT receptor signalling in lung physiology and pathology.
AB  - The WNT signalling cascades have emerged as critical regulators of a wide variety
      of biological aspects involved in lung development as well as in physiological
      and pathophysiological processes in the adult lung. WNTs (secreted glycoproteins)
      interact with various transmembrane receptors and co-receptors to activate
      signalling pathways that regulate transcriptional as well as non-transcriptional
      responses within cells. In physiological conditions, the majority of WNT
      receptors and co-receptors can be detected in the adult lung. However,
      dysregulation of WNT signalling pathways contributes to the development and
      progression of chronic lung pathologies, including idiopathic pulmonary fibrosis
      (IPF), chronic obstructive pulmonary disease (COPD), asthma and lung cancer. The
      interaction between a WNT and the (co-)receptor(s) present at the cell surface is
      the initial step in transducing an extracellular signal into an intracellular
      response. This proximal event in WNT signal transduction with (cell-specific)
      ligand-receptor interactions is of great interest as a potential target for
      pharmacological intervention. In this review we highlight the diverse expression
      of various WNT receptors and co-receptors in the aforementioned chronic lung
      diseases and discuss the currently available biologicals and pharmacological
      tools to modify proximal WNT signalling.

PMID- 29458108
TI  - The relaxin receptor as a therapeutic target - perspectives from evolution and
      drug targeting.
AB  - The peptide relaxin was first identified as an important circulating hormone
      during pregnancy over 90 years ago. Research over many years defined the numerous
      biological roles that relaxin plays throughout pregnancy in many mammalian
      species. These important biological actions have led to the testing of relaxin as
      a therapeutic agent for a number of indications. The discovery of the relaxin
      receptor, RXFP1, in 2002 facilitated the better understanding of the cellular
      targets of relaxin, its mechanism of action and enabled the development of
      relaxin mimetics and screening for small molecule agonists. Additionally, the
      rapid expansion of the genome databases and bioinformatics tools has
      significantly advanced our understanding of the evolution of the relaxin/RXFP1
      signaling system. It is now clear that the relaxin-RXFP1 signaling axis is far
      more ancient than previously appreciated with important roles for invertebrate
      relaxin-like peptides in reproductive and non-reproductive functions. This review
      summarizes these advances as well as developments in drug targeting of RXFP1.
      Hence the complex mode of activation of RXFP1 is discussed as is the discovery
      and development of a peptide mimetic and small molecule agonist. Detailed
      signaling studies are summarized which highlight the cell specific signaling of a
      peptide mimetic and biased signaling of a small molecule agonist. These studies
      highlight the complexities of targeting peptide GPCRs such as RXFP1.

PMID- 29458109
TI  - Modulation of CYP1A1 metabolism: From adverse health effects to chemoprevention
      and therapeutic options.
AB  - The human cytochrome P450 (CYP) 1A1 gene encodes a monooxygenase that metabolizes
      multiple exogenous and endogenous substrates. CYP1A1 has become infamous for its
      oxidative metabolism of benzo[a]pyrene and related polycyclic aromatic
      hydrocarbons, converting these chemicals into very potent human carcinogens.
      CYP1A1 expression is mainly controlled by the aryl hydrocarbon receptor (AHR), a
      transcription factor whose activation is induced by binding of persistent organic
      pollutants, including polycyclic aromatic hydrocarbons and dioxins. Accordingly,
      induction of CYP1A1 expression and activity serves as a biomarker of AHR
      activation and associated xenobiotic metabolism as well as toxicity in diverse
      animal species and humans. Determination of CYP1A1 activity is integrated into
      modern toxicological concepts and testing guidelines, emphasizing the tremendous
      importance of this enzyme for risk assessment and regulation of chemicals.
      Further, CYP1A1 serves as a molecular target for chemoprevention of chemical
      carcinogenesis, although present literature is controversial on whether its
      inhibition or induction exerts beneficial effects. Regarding therapeutic
      applications, first anti-cancer prodrugs are available, which require a metabolic
      activation by CYP1A1, and thus enable a specific elimination of CYP1A1-positive
      tumors. However, the application range of these drugs may be limited due to the
      frequently observed downregulation of CYP1A1 in various human cancers, probably
      leading to a reduced metabolism of endogenous AHR ligands and a sustained
      activation of AHR and associated tumor-promoting responses. We here summarize the
      current knowledge on CYP1A1 as a key player in the metabolism of exogenous and
      endogenous substrates and as a promising target molecule for prevention and
      treatment of human malignancies.

PMID- 29458110
TI  - Investigation of adhesive interactions in the specific targeting of Triptorelin
      conjugated PEG-coated magnetite nanoparticles to breast cancer cells.
AB  - : The understanding of adhesive interaction at the nanoscale between
      functionalized nanoparticles and biological cells is of great importance to
      develop effective theranostic nanocarriers for targeted cancer therapy. Here, we
      report a combination of experimental and computational approaches to evaluate the
      adhesion between Triptorelin (a Luteinizing Hormone-Releasing Hormone (LHRH)
      agonist)-conjugated poly-(ethylene glycol) (PEG)-coated magnetite nanoparticles
      (Triptorelin-MNPs) and breast cells. The adhesion forces between Triptorelin-MNPs
      and normal/cancerous breast cells are obtained using atomic force microscopy. The
      corresponding work of adhesion is then estimated using Johnson-Kendall-Roberts
      model. Our results demonstrate that Triptorelin-MNPs have a fourteen-fold greater
      work of adhesion to breast cancer cells than to normal breast cells. In addition,
      the work of adhesion between Triptorelin-MNPs and breast cancer cells is found to
      be three times more than that between unmodified MNPs and breast cancer cells.
      Hence, the experimental observation indicates that Triptorelin ligands facilitate
      the specific targeting of breast cancer cells. Furthermore, molecular dynamics
      simulations are performed to investigate the molecular origins of the adhesive
      interactions. The simulations reveal that the interactions between molecules
      (e.g. Triptorelin and PEG) and LHRH receptors are dominated by van der Waals
      energies, while the interactions of these molecules with cell membrane are
      dominated by electrostatic interactions. Moreover, both experimental and
      computational results reveal that PEG serves as an effective coating that
      enhances adhesive interactions to breast cancer cells that over-express LHRH
      receptors, while reduces the adhesion to normal breast cells. Our results
      highlight the potential to develop Triptorelin-MNPs into tumor-specific MRI
      contrast agents and drug carriers. STATEMENT OF SIGNIFICANCE: Systematic
      investigation of adhesive interactions between functionalized nanoparticles and
      cancer cells is of great importance in developing effective theranostic
      nanocarriers for targeted cancer therapy. Herein, we use a combination of atomic
      force microscopy technique and molecular dynamics simulations approach to explore
      the adhesive interactions at the nanoscale between Triptorelin-conjugated
      polyethylene glycol (PEG)-coated magnetite nanoparticles and normal/cancerous
      breast cells. This study characterizes and quantifies the work of adhesion, as
      well as adhesion forces, at the nanocarrier/cell interfaces, unravels the
      molecular origins of adhesive interactions and highlights the effectiveness of
      PEG coatings and Triptorelin ligands in the specific targeting of breast cancer
      cells. Our findings expand the fundamental understanding of nanoparticle/cell
      adhesion and provide guidelines for the design of more rational nanocarriers.

PMID- 29458111
TI  - PPARdelta modulation rescues mitochondrial fatty acid oxidation defects in the
      mdx model of muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a recessive, fatal X-linked disease that is
      characterized by progressive skeletal muscle wasting due to the absence of
      dystrophin, which is an a essential protein that bridges the inner cytoskeleton
      and extra-cellular matrix. This study set out to characterize the mitochondria in
      primary muscle satellite cell derived myoblasts from mdx mice and wild type
      control mice. Compared to wild type derived cells the mdx derived cells have
      reduced mitochondrial bioenergetics and have fewer mitochondria. Here, we
      demonstrate that a novel PPARdelta modulator improves mitochondrial function in
      the mdx mice, which supports that modulating PPARdelta may be therapeutically
      beneficial in DMD patients.

PMID- 29458112
TI  - Compatible osmolytes modulate mitochondrial function in a marine osmoconformer
      Crassostrea gigas (Thunberg, 1793).
AB  - Salinity is an important environmental factor affecting physiology of marine
      organisms. Osmoconformers such as marine mollusks maintain metabolic function
      despite changes of the osmolarity and composition of the cytosol during salinity
      shifts. Currently, metabolic responses to the salinity-induced changes of the
      intracellular milieu are not well understood. We studied the effects of
      osmolarity (450 vs. 900 mOsm) and compatible osmolytes (70-590 mM of taurine or
      betaine) on isolated gill mitochondria of a marine osmoconformer, the Pacific
      oyster Crassostrea gigas. Physiological concentrations of taurine enhanced
      mitochondrial ATP synthesis and electron transport system (ETS) capacity,
      increased mitochondrial coupling and stimulated the forward flux through the
      Complex I. Notably, the stimulatory effects of taurine were more pronounced at
      900 mOsm compared to 450 mOsm. In contrast, betaine proportionally increased the
      rates of the mitochondrial proton leak, oxidative phosphorylation and ETS flux
      (with no net effect on the mitochondrial coupling) and suppressed the activity of
      cytochrome c oxidase in oyster mitochondria. However, the effective concentration
      of betaine (590 mM) was higher than typically found in bivalves, and thus betaine
      is not likely to affect oyster mitochondria under the physiological conditions in
      vivo. Our findings indicate that taurine may support the mitochondrial
      bioenergetics during hyperosmotic stress in oysters. Compatibility of taurine
      with the metabolic functions and its beneficial effects on mitochondria may have
      contributed to its broad distribution as an osmolyte in marine osmoconformers and
      might explain the earlier reports of the positive effects of taurine
      supplementation on energy metabolism of other organisms, including mammals.

PMID- 29458113
TI  - Poorer positive affect in response to self-paced exercise among the obese.
AB  - We aimed to investigate the association between body mass index (BMI) and
      affective response, ratings of perceived exertion (RPE), and physiological
      responses during self-paced exercise. Sixty-six women were divided into three
      groups accordingly with the BMI: obese (n = 22: 33.5 +/- 8.5 yr; 34.9 +/- 4.1
      kg?m-2), overweight (n = 22: 34.8 +/- 8.6 yr; 26.4 +/- 1.3 kg?m-2), and normal
      weight (n = 22: 30.8 +/- 9.3 yr; 22.0 +/- 1.6 kg?m-2). They underwent a graded
      exercise test and a 20-min self-paced walking session on a treadmill. Affective
      responses, RPE, heart rate (HR), and oxygen uptake (VO2) were recorded every 5
      min. The women with obesity experienced the lowest affective rates (p < .001),
      despite similar RPE, HR, and VO2 to the other normal weight and overweight
      groups. In addition, a multiple regression model indicated that BMI was a
      significant predictor of affective responses (p < .001). In conclusion, the
      results of the present study suggest that obesity is associated with poorer
      affective responses to exercise even at self-paced intensity, with the same
      physiological responses and perceived exertion. Therefore, techniques that aim
      directly to increase pleasure and/or reduce attentional focus and perception of
      effort in this population are required, such as affect-regulated prescription,
      shorter bouts of self-paced exercise throughout the day, distraction away from
      internal cues (e.g. music, group exercise), etc.

PMID- 29458114
TI  - Severity-dependent influence of isocapnic hypoxia on reaction time is independent
      of neurovascular coupling.
AB  - With exposure to acute normobaric hypoxia, global cerebral oxygen delivery is
      maintained via increases in cerebral blood flow (CBF); therefore, regional and
      localized changes in oxygen tension may explain neurocognitive impairment.
      Neurovascular coupling (NVC) is the close temporal and regional relationship of
      CBF to changes in neural activity and may aid in explaining the localized CBF
      response with cognitive activation. High-altitude related cognitive impairment is
      likely affected by hypocapnic cerebral vasoconstriction that may influence
      regional CBF regulation independent of hypoxia. We assessed neurocognition and
      NVC following 30 min of acute exposure to isocapnic hypoxia (decreased partial
      pressure of end-tidal oxygen; PETO2) during moderate hypoxia (MOD HX; 55 mm Hg
      PETO2), and severe hypoxia (SEV HX; 45 mm Hg PETO2) in 10 healthy individuals
      (25.5 +/- 3.3 yrs). Transcranial Doppler ultrasound was used to assess mean
      posterior and middle cerebral blood velocity (PCAv and MCAv, respectively) and
      neurocognitive performance was assessed via validated computerized tests. The
      main finding was that reaction time (i.e., kinesthetic and visual-motor ability
      via Stroop test) was selectively impaired in SEV HX (-4.6 +/- 5.2%, P = 0.04),
      but not MOD HX, while complex cognitive performance (e.g., psychomotor speed,
      cognitive flexibility, processing speed, executive function, and motor speed) was
      unaffected with hypoxia (P > 0.05). Additionally, severity of hypoxia had no
      effect on NVC (PCAv CON vs. SEV HX relative peak response 13.7 +/- 6.4% vs. 16.2
      +/- 11.5%, P = 0.71, respectively). In summary, severe isocapnic hypoxia impaired
      reaction time, but not complex cognitive performance or NVC. These findings have
      implications for recreational and military personnel who may experience acute
      hypoxia.

PMID- 29458115
TI  - Effect of AceK (acesulfame potassium) on brain function under dietary restriction
      in mice.
AB  - People preferably take zero or low-calorie beverages and foods with artificial
      sweeteners even though it has been recently suggested that long-term artificial
      sweetener use affects physiological functions. In addition, a lower body weight
      was considered to be more healthful, but an abnormally low body weight caused by
      an excessive diet has been reported to cause health problems. Acesulfame
      potassium (AceK) is one of the most commonly used for foods and beverages because
      of its resistance to thermal degradation and marked sweetness. However, the
      combined effect of AceK and a low body weight on the physiological functions
      remains unknown. Here, we investigated the effect of long-term AceK fluid intake
      on the cognitive function under dietary restriction. We administered AceK to mice
      fed a low carbohydrate (LC) diet for 4 weeks, and behavioral assays were then
      performed for a week. The mice fed the LC diet with AceK treatment for 4 weeks
      showed an increase in water intake and a decrease in short-term and object
      cognitive memories in the Y-maze and novel object recognition tests,
      respectively. Mice were sacrificed after behavioral tests to measure glucose
      levels. The glucose levels in the frontal cortex were significantly decreased in
      mice fed the LC diet with AceK treatment in comparison with mice fed the LC diet
      alone, although there was no significant difference in the plasma glucose levels.
      These results suggest that the combination of long-term AceK intake and the LC
      diet affects the cognitive function through the reduction of cortical glucose
      levels.

PMID- 29458116
TI  - Junk food advertising moderates the indirect effect of reward sensitivity and
      food consumption via the urge to eat.
AB  - The current study aimed to identify how underlying individual differences
      increases vulnerability to television food advertising. In particular, this study
      examined how reward sensitivity, a biologically-based predisposition to approach
      rewards (such as appetitive foods) in the environment, influenced participants'
      vulnerability to television food advertising and subsequent food consumption.
      Ninety-eight participants were randomly assigned to a cue condition (food cues
      versus non-food cues) and then viewed a 30 min documentary interrupted by
      advertising featuring a mix of food and neutral advertising (food cue condition)
      or only neutral advertising (non-food cue condition). Participants' reward
      sensitivity, approach motivation measured as urge to eat, and food consumption
      were recorded. Moderated mediation regression analyses revealed the positive
      association between reward sensitivity and food consumption was mediated by an
      increase in urge to eat, but only when participants were exposed to food
      advertising. These findings suggest heightened reward sensitivity, exposure to
      appetitive food cues, and approach motivation are key interacting mechanisms that
      may lead to maladaptive eating behaviours.

PMID- 29458117
TI  - Agomelatine's effect on circadian locomotor rhythm alteration and depressive-like
      behavior in 6-OHDA lesioned rats.
AB  - Parkinson's disease (PD) patients often suffer from circadian locomotor rhythms
      impairment and depression, important non-motor symptoms. It is known that toxin
      based animal models of PD can reproduce these features. In a 6-hydroxydopamine (6
      OHDA) intranigral model, we first investigated the possible disturbances on
      circadian rhythms of locomotor activity. The rats were divided into 6-OHDA and
      Sham groups. After a partial dopaminergic lesion, the 6-OHDA group showed slight
      alterations in different circadian locomotor rhythms parameters. In a second
      experiment, we hypothesized agomelatine, an melatoninergic antidepressant with
      potential to resynchronize disturbed rhythms, could prevent neuronal damage and
      rhythm alterations in the same 6-OHDA model. The animals were divided into four
      groups: 6-OHDA+vehicle, 6-OHDA+ago, Sham+vehicle and 6-OHDA+ago. However, the
      treated animals (agomelatine 50 mg/kg for 22 days) showed an impaired rhythm
      robustness, and agomelatine did not induce significant changes in the other
      circadian parameters nor neuroprotection. Finally, in a third experiment, we
      examined the effects of agomelatine in the 6-OHDA model regarding depressive-like
      behavior, evaluated by sucrose preference test. The animals were also divided
      into four groups: 6-OHDA+vehicle, 6-OHDA+ago, Sham+vehicle and 6-OHDA+ago. The
      toxin infused animals showed a decrease in sucrose preference in comparison with
      the vehicle infused animals, however, agomelatine did not prevent this decrease.
      Our findings indicate that agomelatine worsened circadian locomotor rhythm and
      was not able to reverse the depressive-like behavior of rats in the 6-OHDA PD
      model.

PMID- 29458118
TI  - Neuroprotective effect of melatonin against lipopolysaccharide-induced depressive
      like behavior in mice.
AB  - Accumulating evidence indicates an interaction between inflammation and
      depression since increased levels of pro-inflammatory cytokines are associated
      with depression-related symptoms. Melatonin is a hormone synthesized and secreted
      by the pineal gland with antioxidant, anti-inflammatory and antidepressant-like
      effects. In this way, it would be interesting to evaluate the putative
      antidepressant-like effect of melatonin treatment in an acute inflammation mice
      model of depression. The present study aimed to investigate the effect of
      melatonin treatment on lipopolysaccharide (LPS) induced depressive-like behavior,
      neuroinflammation, oxidative stress and alteration on brain-derived neurotrophic
      fator (BDNF) levels. Mice were treated with melatonin (10 mg/kg, i.p.) 30 min
      before LPS (0.5 mg/kg, i.p.) injection. Twenty-four hours after LPS infusion,
      mice were submitted to the behavioral tests and, thereafter, biochemical
      determinations were performed. Melatonin treatment prevented LPS-induced
      depressive-like behavior in the forced swim and tail suspension tests with no
      alterations in locomotor activity evaluated in the open field test. Melatonin
      attenuated LPS-induced increase in tumor necrosis factor-alpha (TNF-alpha) and
      reduction of BDNF levels in the hippocampus. Treatment with melatonin also
      prevented LPS-induced increase in lipid peroxidation and the reduction of
      glutathione levels in the hippocampus. In conclusion, the present study suggests
      that melatonin treatment exerted neuroprotective effects against LPS-induced
      depressive-like behavior which may be related to reduction of TNF-alpha release,
      oxidative stress and modulation of BDNF expression.

PMID- 29458119
TI  - The Function of HLA-B*13:01 Involved in the Pathomechanism of Dapsone-Induced
      Severe Cutaneous Adverse Reactions.
AB  - Dapsone-induced hypersensitivity reactions may cause severe cutaneous adverse
      reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS).
      It has been reported that HLA-B*13:01 is strongly associated with dapsone-induced
      hypersensitivity reactions among leprosy patients. However, the phenotype
      specificity and detailed immune mechanism of HLA-B*13:01 remain unclear. We
      investigated the genetic predisposition, HLA-B*13:01 function, and cytotoxic T
      cells involved in the pathogenesis of dapsone-induced severe cutaneous adverse
      reactions. We enrolled patients from Taiwan and Malaysia with DRESS and
      maculopapular eruption with chronic inflammatory dermatoses. Our results showed
      that the HLA-B*13:01 allele was present in 85.7% (6/7) of patients with dapsone
      DRESS (odds ratio = 49.64, 95% confidence interval = 5.89-418.13; corrected P =
      2.92 * 10-4) but in only 10.8% (73/677) of general population control individuals
      in Taiwan. The level of granulysin, the severe cutaneous adverse reaction
      specific cytotoxic protein released from cytotoxic T cells, was increased in both
      the plasma of DRESS patients (36.14 +/- 9.02 ng/ml, P < 0.05) and in vitro
      lymphocyte activation test (71.4%, 5/7 patients) compared with healthy control
      individuals. Furthermore, dapsone-specific cytotoxic T cells were significantly
      activated when co-cultured with HLA-B*13:01-expressing antigen presenting cells
      in the presence of dapsone (3.9-fold increase, compared with cells with no HLA
      B*13:01 expression; P < 0.01). This study indicates that HLA-B*13:01 is strongly
      associated with dapsone DRESS and describes a functional role for the HLA
      restricted immune mechanism induced by dapsone.

PMID- 29458120
TI  - Major Role for TRPV1 and InsP3R in PAR2-Elicited Inflammatory Mediator Production
      in Differentiated Human Keratinocytes.
AB  - PAR2 activation in basal keratinocytes stimulates inflammation via the Ca2+
      dependent production of mediators such as IL-1beta, TNF-alpha, and TSLP. In this
      study, we investigated PAR2 calcium signaling and the consequent production of
      inflammatory mediators in differentiated human primary keratinocytes (DhPKs).
      Stimulation with the PAR2-activating peptide SLIGKV promoted Ca2+ store depletion
      in both undifferentiated human primary keratinocytes and DhPKs. SLIGKV-evoked
      Ca2+ store depletion did not trigger the store-operated Ca2+ entry (i.e., SOCE)
      through ORAI1 in DhPKs compared with undifferentiated human primary
      keratinocytes. The inhibition of phospholipase C and the concomitant inhibition
      of TRPV1 and inositol triphosphate receptor in DhPKs abrogated the SLIGKV-evoked
      Ca2+ store depletion; NF-kappaB activity; and the production of inflammatory
      mediators such as IL-1beta, TNF-alpha, and TSLP. Taken together, these results
      indicate a key role for both InsP3R and TRPV1 in Ca2+ internal stores in the PAR2
      evoked Ca2+ release and consequent skin inflammation in DhPKs. These findings may
      provide clues to understanding the pathological role of DhPKs in skin disorders
      in which PAR2 is known to be involved, such as atopic dermatitis, Netherton
      syndrome, and psoriasis.

PMID- 29458121
TI  - The paradox of marrow adipose tissue in anorexia nervosa.
AB  - Anorexia nervosa (AN) is a psychiatric disorder characterized by inappropriate
      nutrient intake resulting in low body weight. Multiple hormonal adaptations
      facilitate decreased energy expenditure in this state of caloric deprivation
      including non-thyroidal illness syndrome, growth hormone resistance, and
      hypogonadotropic hypogonadism. Although these hormonal adaptations confer a
      survival advantage during periods of negative energy balance, they contribute to
      the long-term medical complications associated with AN, the most common of which
      is significant bone loss and an increased risk of fracture. In recent years,
      marrow adipose tissue (MAT) has emerged as an important potential determinant of
      the low bone mass state characteristic of AN. Unlike subcutaneous and visceral
      adipose tissue depots which are low in AN, MAT levels are paradoxically elevated
      and are inversely associated with BMD. In this review, we discuss what is known
      about MAT in AN and the proposed hormonal determinants of this adipose tissue
      depot.

PMID- 29458122
TI  - Regional variations of cortical bone in the humeral head region: A preliminary
      study.
AB  - BACKGROUND: Incidence of proximal humeral fractures dramatically increased over
      the last decade due to demographic changes. The goal of this study was to analyze
      regional characteristics of cortical bone in the humeral head region using
      cortical bone mapping (CBM) technique. METHODS: The proximal humerus of 103
      healthy volunteers was imaged by clinical computed tomography (CT) scans. Three
      groups of volunteers were identified according to age: group A (20-39years),
      group B (40-59years), and group C (>60years). CBM was applied to create color 3D
      thickness maps for each proximal humerus. Cortical parameters, including the
      cortical thickness (CTh), cortical mass surface density (CM), and the
      endocortical trabecular density (ECTD) were measured over humeral head region
      after nine regions of interest (ROI) were defined. RESULTS: Cortical bone
      structure of the humeral head region varied dramatically in cross-section
      independent of age, with significant cortical thinning at the posterior wall.
      Particularly, notable cortical thinning was also found in the distal end of
      lateral wall at 60years of age or older. The degree of regional variability of
      cortical properties within lateral wall tended to diminish with age. CONCLUSION:
      Substantial regional variations in cortical bone structure at humeral head region
      were observed quantitatively in this study. These morphologic data provided
      useful information on clinical medicine such as surgical fixation.

PMID- 29458123
TI  - Osteocyte regulation of bone and blood.
AB  - This past decade has witnessed a renewed interest in the function and biology of
      matrix-embedded osteocytes and these cells have emerged as master regulators of
      bone homeostasis. They secrete two very powerful proteins, sclerostin, a Wnt
      inhibitor, that suppresses bone formation, and receptor-activator of NF-kB ligand
      (RANKL), a cytokine required for osteoclastogenesis. Neutralizing antibodies
      against these proteins are currently used for the treatment of osteoporosis.
      Recent studies however, ascribed yet another function to osteocytes: the control
      of hematopoiesis and the HSPC niche, directly and through secreted factors. In
      the absence of osteocytes there is an increase in HSC mobilization and abnormal
      lymphopoiesis whereas in the absence of Gsalpha signaling in these cells there is
      an increase of myeloid cells. How exactly osteocytes control hematopoiesis or the
      HSPC niche is still not completely understood. In this review we summarize the
      actions of osteocytes in bone and then analyze the effects of these cells on
      hematopoiesis. Future directions and gaps in current knowledge are further
      discussed.

PMID- 29458124
TI  - Tryptophan-mediated Dimerization of the TssL Transmembrane Anchor Is Required for
      Type VI Secretion System Activity.
AB  - The type VI secretion system (T6SS) is a multiprotein complex used by bacteria to
      deliver effectors into target cells. The T6SS comprises a bacteriophage-like
      contractile tail structure anchored to the cell envelope by a membrane complex
      constituted of the TssJ outer-membrane lipoprotein and the TssL and TssM inner
      membrane proteins. TssJ establishes contact with the periplasmic domain of TssM
      whereas the transmembrane segments of TssM and its cytoplasmic domain interact
      with TssL. TssL protrudes in the cytoplasm but is anchored by a C-terminal
      transmembrane helix (TMH). Here, we show that TssL TMH dimerization is required
      for the stability of the protein and for T6SS function. Using the TOXCAT assay
      and point mutations of the 23 residues of the TssL TMH, we identified Thr194 and
      Trp199 as necessary for TssL TMH dimerization. NMR hydrogen-deuterium exchange
      experiments demonstrated the existence of a dimer with the presence of Trp185 and
      Trp199 at the interface. A structural model based on molecular dynamic
      simulations shows that TssL TMH dimer formation involves pi-pi interactions
      resulting from the packing of the two Trp199 rings at the C-terminus and of the
      six aromatic rings of Tyr184, Trp185 and Trp188 at the N-terminus of the TMH.

PMID- 29458125
TI  - Pluripotent Stem Cells for Uncovering the Role of Mitochondria in Human Brain
      Function and Dysfunction.
AB  - Mitochondrial dysfunctions are a known pathogenetic mechanism of a number of
      neurological and psychiatric disorders. At the same time, mutations in genes
      encoding for components of the mitochondrial respiratory chain cause
      mitochondrial diseases, which commonly exhibit neurological symptoms.
      Mitochondria are therefore critical for the functionality of the human nervous
      system. The importance of mitochondria stems from their key roles in cellular
      metabolism, calcium handling, redox and protein homeostasis, and overall cellular
      homeostasis through their dynamic network. Here, we describe how the use of
      pluripotent stem cells (PSCs) may help in addressing the physiological and
      pathological relevance of mitochondria for the human nervous system. PSCs allow
      the generation of patient-derived neurons and glia and the identification of gene
      specific and mutation-specific cellular phenotypes via genome engineering
      approaches. We discuss the recent advances in PSC-based modeling of brain
      diseases and the current challenges of the field. We anticipate that the careful
      use of PSCs will improve our understanding of the impact of mitochondria in
      neurological and psychiatric disorders and the search for effective therapeutic
      avenues.

PMID- 29458127
TI  - Calmodulin-induced Conformational Control and Allostery Underlying Neuronal
      Nitric Oxide Synthase Activation.
AB  - Nitric oxide synthase (NOS) is the primary generator of nitric oxide signals
      controlling diverse physiological processes such as neurotransmission and
      vasodilation. NOS activation is contingent on Ca2+/calmodulin binding at a linker
      between its oxygenase and reductase domains to induce large conformational
      changes that orchestrate inter-domain electron transfer. However, the structural
      dynamics underlying activation of full-length NOS remain ambiguous. Employing
      hydrogen-deuterium exchange mass spectrometry, we reveal mechanisms underlying
      neuronal NOS activation by calmodulin and regulation by phosphorylation. We
      demonstrate that calmodulin binding orders the junction between reductase and
      oxygenase domains, exposes the FMN subdomain, and elicits a more dynamic
      oxygenase active site. Furthermore, we demonstrate that phosphorylation partially
      mimics calmodulin activation to modulate neuronal NOS activity via long-range
      allostery. Calmodulin binding and phosphorylation ultimately promote a more
      dynamic holoenzyme while coordinating inter-domain communication and electron
      transfer.

PMID- 29458128
TI  - Aggregation-prone Regions in HYPK Help It to Form Sequestration Complex for Toxic
      Protein Aggregates.
AB  - Protein aggregates result from altered structural conformations and they can
      perturb cellular homeostasis. Prevention mechanisms, which function against
      protein aggregation by modulatory processes, are diverse and redundant. In this
      study, we have characterized Huntingtin interacting protein K (HYPK) as a global
      aggregation-regulatory protein. We report the mechanistic details of how HYPK's
      aggregation-prone regions allow it to sense and prevent other toxic protein's
      aggregation by forming unique annular-shaped sequestration complexes. Screenings
      for interacting partners of different aggregation-prone proteins identify HYPK as
      a global interacting partner/regulator of Huntingtin97Qexon1, alpha-Synuclein
      A53T and Superoxide dismutase1-G93A. C-terminal hydrophobic region in HYPK makes
      direct contacts with aggregates to initiate the formation of sequestration
      complexes. HYPK acts as aggregate sensor by existing in a seeded amyloid-like
      state which also favors its own concentration-dependent self-oligomerization.
      Oligomerization of HYPK leads to annular and non-fibrillar/amorphous aggregates.
      Two hydrophobic segments in the C-terminus of HYPK are responsible for its own
      aggregations. Self-association of HYPK follows seed nucleation, in which
      oligomeric HYPK seeds nucleate to annular structures. Annular oligomers of HYPK
      fuse with each other to form amorphous aggregates. HYPK shows differential
      interactions with aggregation-prone and non-aggregating proteins, as it
      preferentially binds to aggregation-prone proteins with higher affinity than
      native/non-aggregating proteins. This favors the formation of HYPK's
      sequestration complexes both in cytosol and in ribosome. Besides having
      aggregation-preventive property, HYPK also reduces the cellular level of toxic
      proteins. In vivo, HYPK sequestration complexes prevent the formation of toxic
      protein aggregates to physiologically show positive impact on cell survival and
      restoration of normal cell physiology.

PMID- 29458126
TI  - Structural and Mechanistic Analysis of the Choline Sulfatase from Sinorhizobium
      melliloti: A Class I Sulfatase Specific for an Alkyl Sulfate Ester.
AB  - Hydrolysis of organic sulfate esters proceeds by two distinct mechanisms, water
      attacking at either sulfur (S-O bond cleavage) or carbon (C-O bond cleavage). In
      primary and secondary alkyl sulfates, attack at carbon is favored, whereas in
      aromatic sulfates and sulfated sugars, attack at sulfur is preferred. This
      mechanistic distinction is mirrored in the classification of enzymes that
      catalyze sulfate ester hydrolysis: arylsulfatases (ASs) catalyze S-O cleavage in
      sulfate sugars and arylsulfates, and alkyl sulfatases break the C-O bond of alkyl
      sulfates. Sinorhizobium meliloti choline sulfatase (SmCS) efficiently catalyzes
      the hydrolysis of alkyl sulfate choline-O-sulfate (kcat/KM=4.8*103s-1M-1) as well
      as arylsulfate 4-nitrophenyl sulfate (kcat/KM=12s-1M-1). Its 2.8-A resolution X
      ray structure shows a buried, largely hydrophobic active site in which a
      conserved glutamate (Glu386) plays a role in recognition of the quaternary
      ammonium group of the choline substrate. SmCS structurally resembles members of
      the alkaline phosphatase superfamily, being most closely related to dimeric ASs
      and tetrameric phosphonate monoester hydrolases. Although >70% of the amino acids
      between protomers align structurally (RMSDs 1.79-1.99A), the oligomeric
      structures show distinctly different packing and protomer-protomer interfaces.
      The latter also play an important role in active site formation. Mutagenesis of
      the conserved active site residues typical for ASs, H218O-labeling studies and
      the observation of catalytically promiscuous behavior toward phosphoesters
      confirm the close relation to alkaline phosphatase superfamily members and
      suggest that SmCS is an AS that catalyzes S-O cleavage in alkyl sulfate esters
      with extreme catalytic proficiency.

PMID- 29458129
TI  - Honeysuckle-encoded microRNA2911 inhibits Enterovirus 71 replication via
      targeting VP1 gene.
AB  - Enterovirus 71 (EV71) is the primary pathogen of hand-foot-and-mouth disease
      (HFMD) in children and virus infections are associated with severe neurological
      dysfunctions and even death. MIR2911 is a honeysuckle-encoded atypical microRNA
      with extreme stability. Here, we report that MIR2911 directly inhibits EV71
      replication by targeting the VP1 gene. Bioinformatics prediction and luciferase
      reporter assay showed that MIR2911 could target the VP1 gene of EV71.
      Transfection experiments using synthetic MIR2911 and extracted RNA from HS
      decoction shown that each of these preparations was capable of inhibiting EV71
      VP1 protein expression; however, these preparations did not impact EV71 mutants
      in which the MIR2911-binding sites were mutated. Furthermore, EV71 replication
      was increased by antagomirs against MIR2911 in the HS decoction, implying that
      MIR2911 was physiologically functional in controlling EV71 replication in vitro.
      These results indicated that, by targeting VP1 gene, MIR2911 may effectively
      inhibit EV71 replication. Our results also provide a potential novel strategy on
      the therapy and/or prevention of HFMD originating from EV71 virus infection.

PMID- 29458130
TI  - Impact of RNA polymerase I inhibitor CX-5461 on viral kinase-dependent and 
      independent cytomegalovirus replication.
AB  - Human cytomegalovirus (HCMV) infections cause congenital birth defects and
      disease in immunosuppressed individuals. Antiviral compounds can control
      infection yet their use is restricted due to concerns of toxicity and the
      emergence of drug resistant strains. We have evaluated the impact of an RNA
      Polymerase I (Pol I) inhibitor, CX-5461 on HCMV replication. CX-5461 inhibits Pol
      I-mediated ribosomal DNA transcription by binding G-quadruplex DNA structures and
      also activates cellular stress response pathways. The addition of CX-5461 at both
      early and late stages of the HCMV infection inhibited viral DNA synthesis and
      virus production. Interestingly, adding CX-5461 after the onset of viral DNA
      synthesis resulted in a greater reduction compared to continuous treatment
      starting early during infection. We observed an accompanying increase in cyclin
      dependent kinase inhibitor p21 in infected cells treated late but not early which
      likely explains the differences. Our previous studies demonstrated the importance
      of p21 in the antiviral activity of the HCMV kinase inhibitor, maribavir.
      Addition of CX-5461 increased the anti-HCMV activity of maribavir. Our data
      demonstrate that CX-5461 inhibits HCMV replication and synergizes with maribavir
      to disrupt infection.

PMID- 29458131
TI  - Inhibition of hepatitis B virus replication via HBV DNA cleavage by Cas9 from
      Staphylococcus aureus.
AB  - Chronic hepatitis B virus (HBV) infection is difficult to cure due to the
      presence of covalently closed circular DNA (cccDNA). Accumulating evidence
      indicates that the CRISPR/Cas9 system effectively disrupts HBV genome, including
      cccDNA, in vitro and in vivo. However, efficient delivery of CRISPR/Cas9 system
      to the liver or hepatocytes using an adeno-associated virus (AAV) vector remains
      challenging due to the large size of Cas9 from Streptococcus pyogenes (Sp). The
      recently identified Cas9 protein from Staphylococcus aureus (Sa) is smaller than
      SpCas9 and thus is able to be packaged into the AAV vector. To examine the
      efficacy of SaCas9 system on HBV genome destruction, we designed 5 guide RNAs
      (gRNAs) that targeted different HBV genotypes, 3 of which were shown to be
      effective. The SaCas9 system significantly reduced HBV antigen expression, as
      well as pgRNA and cccDNA levels, in Huh7, HepG2.2.15 and HepAD38 cells. The dual
      expression of gRNAs/SaCas9 in these cell lines resulted in more efficient HBV
      genome cleavage. In the mouse model, hydrodynamic injection of gRNA/SaCas9
      plasmids resulted in significantly lower levels of HBV protein expression. We
      also delivered the SaCas9 system into mice with persistent HBV replication using
      an AAV vector. Both the AAV vector and the mRNA of Cas9 could be detected in the
      C3H mouse liver cells. Decreased hepatitis B surface antigen (HBsAg), HBV DNA and
      pgRNA levels were observed when a higher titer of AAV was injected, although this
      decrease was not significantly different from the control. In summary, the SaCas9
      system accurately and efficiently targeted the HBV genome and inhibited HBV
      replication both in vitro and in vivo. The system was delivered by an AAV vector
      and maybe used as a novel therapeutic strategy against chronic HBV infection.

PMID- 29458132
TI  - Therapeutic drug monitoring in treatment-experienced HIV-infected patients
      receiving darunavir-based salvage regimens: A case series.
AB  - Therapeutic drug monitoring (TDM) constitutes a compelling approach for the
      optimization of antiretroviral therapy in treatment-experienced HIV-1 patients.
      While various inhibitory indices have been proposed to predict virologic outcome,
      there is a lack of consensus on the clinical value of TDM. Here, we report the
      comparative results of TDM in 14 HIV-1-infected patients who had previously
      received at least two different PI-based regimens and who initiated darunavir
      (DRV)-based salvage therapy. Pharmacokinetic/pharmacodynamics (PK/PD) parameters
      were calculated for each subject. Seventy-nine percent of subjects had a viral
      load <50 copies/mL at 48 weeks. The only subject with two consecutive viral loads
      >50 copies/mL at the end of the study period was the patient with the lowest
      instantaneous inhibitory potential (IIP). The sample size was insufficient to
      show an association between any of the PK/PD parameters and virologic response.
      Based on our observations, we suggest that the utility of IIP for antiretroviral
      combinations for the prediction of virologic outcome in HIV-1 drug-experienced
      patients should be studied further.

PMID- 29458133
TI  - Artesunate-derived monomeric, dimeric and trimeric experimental drugs - Their
      unique mechanistic basis and pronounced antiherpesviral activity.
AB  - Human cytomegalovirus (HCMV) is a major human pathogen and is associated with
      severe pathology, such as life-threatening courses of infection in
      immunocompromised individuals and neonates. Currently, antiviral therapy is still
      hampered by a considerable toxicity of the available drugs and induction of viral
      resistance. Recently, we and others reported the very potent antiviral activity
      of the broad antiinfective drug artesunate in vitro and in vivo. Here, we
      investigated further optimized analogs including monomeric, dimeric and trimeric
      derivatives belonging to this highly interesting chemical group of experimental
      drugs (sesquiterpenes/trioxanes) and compared these to the previously identified
      trimeric artesunate compound TF27. We could demonstrate that (i) seven of the
      eight investigated monomeric, dimeric and trimeric artesunate derivatives, i.e.
      TF79, TF85, TF87, TF93.2.4, TF111, TF57a and TF57ab, exerted a strong anti-HCMV
      activity in primary human fibroblasts, (ii) the EC50 values ranged in the low to
      sub-micromolar concentrations and indicated a higher antiviral potency than the
      recently described artesunate analogs, (iii) one trimeric compound, TF79, showed
      a very promising EC50 of 0.03 +/- 0.00 MUM, which even exceled the antiviral
      potency of TF27 (EC50 0.04 +/- 0.01 MUM), (iv) levels of cytotoxicity
      (quantitative measurement of lactate dehydrogenase release) were low in a range
      between 100 and 30 MUM and thus different from antiviral concentrations, (v) an
      analysis of protein expression levels indicated a potent block of viral protein
      expression, and (vi) data from a NF-kappaB reporter cell system strongly
      suggested that these compounds share the same antiviral mechanism. Taken
      together, our data on these novel compounds strongly encourages our earlier
      concept on the oligomerization and hybridization of artesunate analogs, providing
      an excellent platform for the generation of antiherpesviral drugs.

PMID- 29458134
TI  - Antiviral activity of pyrrole-imidazole polyamides against SV40 and BK
      polyomaviruses.
AB  - The ability of antiviral polyamides (AVP) to act upon polyomaviruses (PyV) was
      evaluated. Initial studies found that a single treatment of AVP protected SV40
      infected BSC-1 cells from cytopathic effect (CPE) for as long as 11 days p.i..
      AVP substantially suppressed SV40 genome copy numbers over the duration of the
      experiment. Immunofluorescence analysis of ataxia-telangiectasia mutated (ATM)
      activation and large T antigen (LTag) expression clearly demonstrated that AVP
      treatment at day 1 p.i. delayed the onset of productive SV40 replication by
      approximately 3 days, and substantially limited the infection relative to vehicle
      treated controls. AVP dose-response experiments recorded IC50s in the low nM
      range that were similar to IC50s previously reported for HPV16. The ability of
      AVPs to act on BKPyV was next examined. Again, IC50s in the low nM range were
      obtained with the exception of an AVP (PA1) that gave an IC50 of 437 nM against
      the BKPyV Dunlop strain. The Mre11 inhibitor Mirin substantially reduced the AVP
      IC50 against SV40 demonstrating that Mre11 protects PyV genomes from AVP action
      as previously shown for HPV. Together these experiments show that AVPs are potent
      antiviral agents for PyV that act via a mechanism with similarities to that found
      for HPV. The results demonstrate that AVPs are useful tools for controlling and
      studying PyV biology. The potential use of these agents against BKPyV and other
      PyV pathogens also has clinical implications.

PMID- 29458135
TI  - Porcine heart interatrial septum anatomy.
AB  - BACKGROUND: The left-sided atrial septal pouch (SP), a recently re-discovered
      anatomical structure within the human interatrial septum, has emerged as a
      possible source of thrombi formation and a trigger for atrial fibrillation,
      thereby potentially increasing the risk for ischemic stroke. In many studies, the
      swine interatrial septum has been used as model of the human heart. Also,
      possible new strategies and devices for management of the SPs may first be tested
      in this pig model. Therefore, in this study, we aimed to evaluate swine
      interatrial septum morphology and to compare it with the human analog, especially
      in the light of SP occurrence. METHODS: A total of 75 swine (Sus scrofa f.
      domestica) hearts were examined. The interatrial septum morphology was assessed,
      and SPs were measured. RESULTS: The most common variant of the interatrial septum
      was smooth septum (26.6%) followed by the patent foramen ovale channel and right
      SP (both 22.7%). No left or double SPs were observed. In 28.0% of all cases the
      fold of tissue (left septal ridge) was observed on the left side of the
      interatrial septum in the location where the left-sided SP should be expected.
      The mean length of the patent foramen ovale channel was 7.1+/-1.5mm. The mean
      right SP depth was 6.3+/-2.2mm, and its ostium width and height were 5.8+/-1.2
      and 5.3+/-1.6mm, respectively. CONCLUSIONS: There are significant differences
      between human and porcine interatrial septum morphology that should be taken into
      account during experimental studies. The absence of the left SP in swine results
      in the inability to use porcine heart as an experimental model for left-sided SP
      management.

PMID- 29458136
TI  - Changes in anatomic position of root canal orifices in pluriradicular teeth
      following re-location during endodontic treatment.
AB  - Direct access to the root canals in posterior teeth for endodontic treatment is
      most frequently facilitated by the straightening of the coronal parts of the root
      canals, having as a consequence the relocation of the canal orifices on the map
      of the floor of the pulp chamber (Christie and Thompson, 1994). This procedure
      intentionally moves the coronal aspect of a canal away from the center of the
      chamber, while simultaneously removing internal dentin from the pulp chamber
      walls. The aim of this study was to evaluate the displacement resulting from the
      relocation of root canal orifices during the initial phase of rotary root canal
      treatment in molars using the dental operating microscope (DOM) and digital image
      processing. Forty-three molars (17 maxillary and 26 mandibular) belonging to 43
      patients (aged 18-62 years) with indications for root canal treatment were
      endodontically treated. The differences between the initial perimeter and the
      perimeter of the root canal orifices polygon after relocation varied between 2.7
      and 3.4MUm (mean 3.0MUm), while the differences between the initial area and the
      area after relocation varied between 2,448,456.8 and 3,249,306.6MUm2 (mean
      2,848,881.7). The increase in access to the cavities and the alterations of the
      pulp chambers can be satisfactorily approximated by the variations of the
      perimeters and areas of the pulp floor polygons during root canal treatment. From
      a clinical perspective, these results indicate that there is a significant
      decrease in tooth substance in molars (except MB2).

PMID- 29458137
TI  - Bisphenol A alters oocyte maturation by prematurely closing gap junctions in the
      cumulus cell-oocyte complex.
AB  - In ovarian follicles, cumulus cells communicate with the oocyte through gap
      junction intercellular communication (GJIC), to nurture the oocyte and control
      its meiosis arrest and division. Bisphenol A (BPA) is a monomer found in
      polycarbonate-made containers that can induce functional alterations, including
      impaired oocyte meiotic division and reduced molecule transfer in GJIC. However,
      how BPA alters oocyte meiotic division is unclear. We investigated whether BPA
      effects on oocyte meiotic division were correlated with reduced transfer in GJIC.
      Cumulus cell-oocyte complexes (COCs) isolated from mouse preovulatory follicles
      were cultured with 0, 0.22, 2.2, 22, 220, and 2200 nM BPA for 2 h. An additional
      16-h incubation with epidermal growth factor (EGF) was performed to promote the
      occurrence of meiotic resumption and progression to metaphase II. Without EGF
      stimulus, BPA treatment increased the percentage of oocytes undergoing meiotic
      resumption, decreased GJIC in the COCs, and did not modify GJIC gene (Cx43 and
      Cx37) and protein (CX43) expression. Following EGF stimulus, BPA increased the
      percentage of oocytes that remained at the anaphase and telophase stages, and
      decreased the percentage of oocytes reaching the metaphase II stage.
      Concomitantly, BPA reduced the expansion of cumulus cells. Carbenoxolone (a GJIC
      inhibitor) and 6-diazo-5-oxo-l-norleucine (a cumulus cell-expansion inhibitor)
      exerted effects on meiotic division similar to those exerted by BPA. These data
      suggest that BPA accelerates meiotic progression, leading to impaired prophase I
      to-metaphase II transition, and that this adverse effect is correlated with
      reduced bidirectional communication in the COC.

PMID- 29458138
TI  - Pharmacokinetic and pharmacodynamic evaluation of 5-methoxy-2-aminoindane (MEAI):
      A new binge-mitigating agent.
AB  - 5-Methoxy-2-aminoindane (MEAI) is a novel psychoactive aminoindane derivative,
      exerting euphoric, alcohol-like tipsy experience and reduced desire to consume
      alcoholic beverages. Our previous toxicological evaluation of MEAI in rats,
      clearly indicated MEAI's potential to be further evaluated as a promising binge
      mitigating agent due to its favorable safety profile. In the light of these
      observations, we have determined MEAI's pharmacokinetic (PK) profile in rats and
      evaluated in-vitro its pharmacodynamics (PD) profile. Following oral and
      intravenous administration of MEAI, two metabolites were identified, namely, N
      acetyl-MEAI and 5-hydroxy-N-acetyl-AI, arising from N-acetylation and oxidative
      demethylation. The PK-parameters of MEAI and N-acetyl-MEAI were derived from
      single i.v. bolus (10 mg/kg) and single oral doses (10 and 90 mg/kg) of MEAI to
      rats. MEAI displayed extensive total clearance (2.8 L/h/kg) and a very short
      plasma and brain half-life (0.5-0.7 h). At 10 mg/kg, MEAI displayed low oral
      bioavailability (25%) and a plasma to brain ratio in the range of 3-5.5, with
      brain MEAI peak levels attained rapidly. Non-linear pharmacokinetic behavior was
      observed in the 90 mg/kg oral group, in which the bioavailability increased by
      500%. The non-linear behavior was also evident by the significant increase in
      plasma half-life of MEAI and its metabolite, N-acetyl-MEAI. N-acetyl-MEAI levels
      in plasma and brain were about ten times lower than the parent compound,
      indicative of its minor contribution to MEAI's pharmacological effect. MEAI
      displayed weak to moderate ligand binding inhibition at the 5-HT2B receptor,
      while the remaining neurochemical targets were unaffected. Further studies, in
      non-rodent species are required, in-order to assess MEAI's PK and PD profile
      adequately.

PMID- 29458139
TI  - Molecular and tissue alterations of collagens in fibrosis.
AB  - The collagen network is altered in fibrotic diseases associated with
      extracellular matrix (ECM) biosynthesis and remodeling. This mini-review focuses
      on the quantitative and qualitative modifications of collagens occurring at the
      molecular and tissue levels in fibrosis. They result from changes in collagen
      expression, biosynthesis, enzymatic cross-linking and degradation by several
      protease families. These molecular modifications, which are mostly regulated by
      TGF-beta, are associated with altered collagen organization at the tissue level,
      leading to a fibrotic signature that can be analyzed by Second Harmonic
      Generation (SHG) microscopy.

PMID- 29458140
TI  - Hyaluronan in adipogenesis, adipose tissue physiology and systemic metabolism.
AB  - Hyaluronic acid (HA, also known as hyaluronan), is a non-sulfated linear
      glycosaminoglycan polymer consisting of repeating disaccharide units of d
      glucuronic acid and N-acetyl-d-glucosamine abundantly present in the
      extracellular matrix. The sizes of hyaluronic acid polymers range from 5000 to
      20,000,000 Da in vivo, and the functions of HA are largely dictated by its size.
      Due to its high biocompatibility, HA has been commonly used as soft tissue filler
      as well as a major component of biomaterial scaffolds in tissue engineering.
      Several studies have implicated that HA may promote differentiation of adipose
      tissue derived stem cells in vitro or in vivo when used as a supporting scaffold.
      However, whether HA actually promotes adipogenesis in vivo and the subsequent
      metabolic effects of this process are unclear. This review summarizes some recent
      publications in the field and discusses the possible directions and approaches
      for future studies, focusing on the role of HA in the adipose tissue.

PMID- 29458141
TI  - Long non-coding RNAs within the tumour microenvironment and their role in tumour
      stroma cross-talk.
AB  - Long non-coding RNAs (lncRNAs) are a diverse class of RNA transcripts which have
      limited protein coding potential. They perform a variety of cellular functions in
      health, but have also been implicated during malignant transformation. A further
      theme in recent years is the critical role of the tumour microenvironment and the
      dynamic interactions between cancer and stromal cells in promoting invasion and
      disease progression. Whereas the contribution of deregulated lncRNAs within
      cancer cells has received considerable attention, their significance within the
      tumour microenvironment is less well understood. The tumour microenvironment
      consists of cancer-associated stromal cells and structural extracellular
      components which interact with one another and with the transformed epithelium
      via complex extracellular signalling pathways. LncRNAs are directly and
      indirectly involved in tumour/stroma cross-talk and help stimulate a permissive
      tumour microenvironment which is more conducive for invasive tumour growth.
      Furthermore, lncRNAs play key roles in determining the phenotype of cancer
      associated stromal cells and contribute to angiogenesis and immune evasion
      pathways, extracellular-matrix (ECM) turnover and the response to hypoxic stress.
      Here we explore the multifaceted roles of lncRNAs within the tumour
      microenvironment and their putative pathophysiological effects.

PMID- 29458142
TI  - Insufficient radiofrequency ablation promotes proliferation of residual
      hepatocellular carcinoma via autophagy.
AB  - Radiofrequency ablation (RFA) is considered to be a potentially curative therapy
      for hepatocellular carcinoma (HCC). However, insufficient RFA (IRFA) can promote
      rapid progression of the residual tumor. The mechanisms underlying IRFA-induced
      tumor promotion remain poorly understood. In the present study, we have
      established a subcutaneous xenograft mouse model and monitored the location and
      extent of IRFA by dual monitoring with ultrasonography and a thermal imager. For
      the first time, we provide evidence of the activation of autophagic pathways in
      mice exposed to IRFA. We show that autophagy plays an important role in relapse
      and proliferation after IRFA and that hydroxychloroquine (HCQ) can suppress these
      effects. Our findings indicate that autophagy is involved in experimental IRFA
      and that inhibition of autophagy may be a novel approach in the treatment of
      local recurrences of HCC after IRFA in the clinic.

PMID- 29458143
TI  - SUV39H2 promotes colorectal cancer proliferation and metastasis via tri
      methylation of the SLIT1 promoter.
AB  - Suppressor of variegation 3-9 homolog 2 (SUV39H2) is a member of the SUV39H
      subfamily of lysine methyltransferases. Its role in colorectal cancer (CRC)
      proliferation and metastasis has remained unexplored. Here, we determined that
      SUV39H2 was upregulated in CRC tissues compared with that in adjacent non
      neoplastic tissues. Further statistical analysis revealed that high SUV39H2
      expression was strongly associated with distant metastasis (P = 0.016) and TNM
      stage (P = 0.038) and predicted a shorter overall survival (OS; P = 0.018) and
      progression-free survival (PFS; P = 0.018) time for CRC patients. Both in vitro
      and in vivo assays demonstrated that ectopically expressed SUV39H2 enhanced CRC
      proliferation and metastasis, while SUV39H2 knockdown inhibited CRC proliferation
      and metastasis. A molecular screen of SUV39H2 targets found that SUV39H2
      negatively regulated the expression of SLIT guidance ligand 1 (SLIT1). Moreover,
      rescue assays suggested that SLIT1 could antagonize the function of SUV39H2 in
      CRC. Mechanistic studies indicated that SUV39H2 can directly bind to the SLIT1
      promoter, suppressing SLIT1 transcription by catalyzing histone H3 lysine 9
      (H3K9) tri-methylation. In summary, we propose that SUV39H2 can predict CRC
      patient prognosis and stimulate CRC malignant phenotypes via SLIT1 promoter tri
      methylation.

PMID- 29458144
TI  - Disruption of peroxisome function leads to metabolic stress, mTOR inhibition, and
      lethality in liver cancer cells.
AB  - Peroxisome houses a large number of enzymes involved in lipid and phytochemical
      oxidation as well as synthesis of bile acid and other specialized lipids.
      Peroxisome resident enzymes are imported into the organelle via a conserved cargo
      transport system composed of many peroxins, protein factors essential for the
      biogenesis of peroxisome. Among the peroxins, PEX5 plays a transporter role, and
      PEX2, 10, and 12 are thought to form a complex that functions as an E3 ubiquitin
      ligase to help recycle PEX5 in an ubiquitin modification-dependent process.
      Previous studies have demonstrated the importance of peroxins in postnatal
      development especially the development of nerve systems. These studies also show
      that peroxins or the function of peroxisomes is dispensable for cellular
      viability. In contrast, however, we report here that PEX2 and other peroxins are
      essential for the viability of liver cancer cells, probably through altering
      metabolism and signaling pathways. Our results suggest that peroxins may be
      potential targets of therapeutics against liver cancer.

PMID- 29458145
TI  - The C/EBPbeta-LINC01133 axis promotes cell proliferation in pancreatic ductal
      adenocarcinoma through upregulation of CCNG1.
AB  - Long non-coding RNAs (lncRNAs) are emerging as important regulators and
      prognostic markers of multiple cancers. Our aim was to determine functional
      involvement of lncRNAs in pancreatic ductal adenocarcinoma (PDAC). In this study,
      we report that LINC01133 expression is higher in PDAC tissues compared to
      adjacent non-cancerous tissues, and this overexpression is associated with poorer
      prognosis among the patients. In vitro, a knockdown of LINC01133 substantially
      decreased PDAC cell proliferation. Tumorigenicity of PDAC cells with the
      LINC01133 knockdown was significantly impaired in a xenograft model assay.
      Moreover, we determined that CCAAT/enhancer-binding protein beta (C/EBPbeta)
      positively regulates LINC01133 expression by binding to the response elements
      within the LINC01133 promoter. Higher expression of C/EBPbeta was observed in
      PDAC tissues, and this overexpression was also associated with the poorer
      prognosis. Furthermore, the LINC01133 knockdown decreased cyclin G1 (CCNG1)
      expression. Overexpression of CCNG1 attenuated the LINC01133 silencing-induced
      impairment of proliferation in PDAC cells. In summary, our findings revealed that
      the C/EBPbeta-LINC01133 axis performs an oncogenic function in PDAC by activating
      CCNG1, which may serve as a prognostic biomarker or a therapeutic target in PDAC.

PMID- 29458146
TI  - Enhanced anticancer effects of Scutellaria barbata D. Don in combination with
      traditional Chinese medicine components on non-small cell lung cancer cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Experience-based herbal medicine as a
      complementary to modern western medicine has triggered an array of studies in
      quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used
      to treat different types of cancers, but its molecular mechanism of action is not
      clearly understood. In this study, we attempted to elucidate the mode of action
      of a traditional Chinese medicine prescription with a total of 14 components,
      named Lian-Jia-San-Jie-Fang (LJSJF, in Chinese), where SB works as the
      "principle" against non-small cell lung cancer (NSCLC) cells. MATERIALS AND
      METHODS: Four different NSCLC cell lines (A549, H460, H1650, and H1975) were
      used. Cytotoxicity, in vitro tumorigenicity, gene expression, and protein
      expression were analyzed by MTT assay, soft agar assay, real-time PCR, and
      Western blots, respectively. RESULTS: Among the 14 components in LJSJF, SB was
      the only one to possess cytotoxic effects at its pharmacologically relevant
      doses. Additionally, we observed synergistically dose-dependent cytotoxic effects
      of SB in combination with other LJSJF components. After SB or LJSJF treatment,
      significant reductions in colony number and/or size were observed in A549 and
      H460; a notable dose-dependent decrease in EGFR was observed in A549, H460, and
      H1650; significant downregulation in EGFR and its downstream signaling targets
      mTOR and p38MAPK were also observed in A549 and H460; and p53 and p21 were
      significantly increased while survivin, cyclin D1, and MDM2 were significantly
      decreased in A549. Additionally, p53, p21, and Mettl7b were decreased, but p73
      was increased in H460. Neither EGFR nor p53 was changed in H1975. Therefore, SB
      or LJSJF may induce cytotoxic effects by regulating multiple and/or distinct
      apoptotic pathways in different NSCLC cells. CONCLUSION: LJSJF exerts more
      pronounced cytotoxic effects against NSCLC cells than SB does by synergistically
      regulating the underlining molecular mechanisms including EGFR and/or p53
      signaling pathways.

PMID- 29458147
TI  - Sessein and isosessein with anti-inflammatory, antibacterial and antioxidant
      activity isolated from Salvia sessei Benth.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia sessei Benth, popularly known as
      "pipilolxochitl" or "sabanito", is a plant utilized in Mexico in traditional
      medicine for the treatment of erysipela. To date, only one report, to our
      knowledge, has been found in which a royleanone-type diterpene of the aerial
      parts of the species was isolated but, again to our knowledge, studies have not
      been conducted on the pharmacological activity of extracts and compounds isolated
      from this plant. AIM OF THE STUDY: The objective of the study was to evaluate the
      anti-inflammatory, antibacterial and antioxidant activity of the organic extracts
      of the aerial parts of Salvia sessei Benth and sessein and isosessein isomers
      isolated from this. MATERIALS AND METHODS: Anti-inflammatory activity was
      evaluated in a model of edema in mouse ear at 1 mg/ear of the isolated extracts
      and compounds (1 and 2), a dose-response curve was performed on these latter and
      one-half of the effective dose (ED50) was determined; antibacterial activity was
      determined through minimal inhibitory concentration (MIC) by microdilution at
      100, 50, 25, and 12.5 ug/mL, and antioxidant capacity, by means of DPPH, ABTS,
      and FRAP assays where, for the first two assays noted, the inhibitory
      concentration 50% (IC50) was calculated for the extracts as well as for the
      compounds isolated. RESULTS: The hexanic extracts (40.55 +/- 0.5%),
      dichloromethanic (56.01 +/- 1.1%) and methanolic (66.05 +/- 0.3%), as well as
      isolated compounds 1 (79.85 +/- 3.5%) and 2 (54.36 +/- 1.7%), demonstrated anti
      inflammatory activity; the methanolic extract presented the greatest percentage
      of inhibition, while isolated compounds 1 and 2 did not present a difference in
      their ED50; additionally, compound 1 exerted a similar effect to that of the drug
      of-reference at the same dose (75.24 +/- 2.4%). The antibacterial activity of the
      extracts and compounds was principally against Gram-positive bacteria: the
      hexanic extract presented activity against Staphylococcus hominis and the
      methanolic and dichloromethanic extracts, and compound 1 exhibited activity
      against Staphylococcus haemolyticus, S. hominis, E. faecalis, in addition to that
      Escherichia coli was sensitive to compound 1, while isomer 2 showed activity
      against Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus
      epidermis and Streptococcus pyogenes bacteria related to erysipela. In the three
      assays, the extract demonstrating greatest antioxidant capacity was the
      methanolic extract, while that of the isolated compounds was compound 1.
      CONCLUSIONS: The results show that the three extracts evaluated in the three
      models presented activity and the chromatographic separation of the
      dichloromethanic extract permitted the isolation of compounds 1 and 2 royleanone
      type isomers, which also presented significant activities such as anti
      inflammatory, antibacterial and antioxidant, thus validate the use of this
      species in traditional medicine.

PMID- 29458148
TI  - Untimely oxidative stress in beta-cells leads to diabetes - Role of circadian
      clock in beta-cell function.
AB  - Diabetes results from a loss of beta-cell function. With the number of people
      with diabetes reaching epidemic proportions globally, understanding mechanisms
      that are contributing to this increasing prevalence is critical. One such factor
      has been circadian disruption, with shift-work, light pollution, jet-lag,
      increased screen time, all acting as potential contributory factors. Though
      circadian disruption has been epidemiologically associated with diabetes and
      other metabolic disorders for many decades, it is only recently that there has
      been a better understanding of the underlying molecular mechanisms. Experimental
      circadian disruption, via manipulation of environmental or genetic factors using
      gene-deletion mouse models, has demonstrated the importance of circadian rhythms
      in whole body metabolism. Genetic disruption of core clock genes, specifically in
      the beta-cells in mice, have, now demonstrated the importance of the intrinsic
      beta-cell clock in regulating function. Recent work has also shown the
      interaction of the circadian clock and enhancers in beta-cells, indicating a
      highly integrated regulation of transcription and cellular function by the
      circadian clock. Disruption of either the whole body or only the beta-cell clock
      leads to significant impairment of mitochondrial function, uncoupling, impaired
      vesicular transport, oxidative stress in beta-cells and finally impaired glucose
      stimulated insulin secretion and diabetes. In this review, we explore the role of
      the circadian clock in mitigating oxidative stress and preserving beta-cell
      function.

PMID- 29458149
TI  - Age-dependent oxidation of extracellular cysteine/cystine redox state
      (Eh(Cys/CySS)) in mouse lung fibroblasts is mediated by a decline in Slc7a11
      expression.
AB  - Aging is associated with progressive oxidation of the extracellular environment.
      The redox state of human plasma, defined by the concentrations of cysteine (Cys)
      and cystine (CySS), becomes more oxidized as we age. Recently, we showed that
      fibroblasts isolated from the lungs of young and old mice retain this
      differential phenotype; old cells produce and maintain a more oxidizing
      extracellular redox potential (Eh(Cys/CySS)) than young cells. Microarray
      analysis identified down-regulation of Slc7a11, the light subunit of the
      CySS/glutamate transporter, as a potential mediator of age-related oxidation in
      these cells. The purpose of the present study was to investigate the mechanistic
      link between Slc7a11 expression and extracellular Eh(Cys/CySS). Sulforaphane
      treatment or overexpression of Slc7a11 was used to increase Slc7a11 in lung
      fibroblasts from old mice, and sulfasalazine treatment or siRNA-mediated knock
      down was used to decrease Slc7a11 in young fibroblasts. Slc7a11 mRNA levels were
      measured by real-time PCR, Slc7a11 activity was determined by measuring the rate
      of glutamate release, Cys, CySS, glutathione (GSH) and its disulfide (GSSG) were
      measured by HPLC, and Eh(Cys/CySS) was calculated from the Nernst equation. The
      results showed that both Eh(Cys/CySS) and Eh(GSH/GSSG) were more oxidized in the
      conditioned media of old cells than in young cells. Up-regulation of Slc7a11 via
      overexpression or sulforaphane treatment restored extracellular Eh(Cys/CySS) in
      cultures of old cells, whereas down-regulation reproduced the oxidizing
      Eh(Cys/CySS) in young cells. Only sulforaphane treatment was able to increase
      total GSH and restore Eh(GSH/GSSG), whereas overexpression, knock down and
      sulfasalazine had no effect on these parameters. In addition, inhibition of GSH
      synthesis with buthionine sulfoximine had no effect on the ability of cells to
      restore their extracellular redox potential in response to an oxidative
      challenge. In conclusion, our study reveals Slc7a11 is the key regulator of age
      dependent changes in extracellular Eh(Cys/CySS) in primary mouse lung
      fibroblasts, and its effects are not dependent on GSH synthesis.

PMID- 29458150
TI  - PINK1 Protects Auditory Hair Cells and Spiral Ganglion Neurons from Cisplatin
      induced Ototoxicity via Inducing Autophagy and Inhibiting JNK Signaling Pathway.
AB  - Phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1) gene
      encodes a serine/threonine kinase, which acts as a molecular sensor of
      mitochondrial health necessary for mitochondrial quality control. The present
      study was designed to examine whether PINK1 expressed in C57BL/6 murine cochlea
      and HEI-OC1 cells and, if so, to investigate the possible mechanisms underlying
      the action of PINK1 in cisplatin-induced death of sensory hair cells (HCs) and
      spiral ganglion neurons (SGNs) in vitro. The expression pattern of PINK1,
      formation of parkin particles, and autophagy were determined by immunofluorescent
      staining. The expressions of PINK1, LC3B, cleaved-caspase 3 and p-JNK were
      measured by Western blotting. The levels of reactive oxygen species (ROS) were
      evaluated by DCFH-DA and Mito-Sox Red staining. The mitochondrial membrane
      potential was detected by Tetramethylrhodamine methyl ester perchlorate (TMRM)
      and Rhodamine 123. Cell viability and apoptosis were examined by CCK8 assay,
      TUNEL staining and Annexin V Apoptosis Detection Kit, respectively. We found that
      PINK1 was widely expressed in the cytoplasm in HCs, SGNs, stria vascularis of
      C57BL/6 cochlea and HEI-OC1 cells and, notably, the expression level in cochlear
      HCs and SGNs of postnatal day 4 (P4) mice was higher than that in adult mice.
      Moreover, treatment with 30 MUM cisplatin elicited the formation of ROS, which,
      in turn, led to PINK1 activation, parkin recruitment, autophagy formation and JNK
      pathway relevant to apoptosis in HEI-OC1 cells, HCs, and SGNs. Meanwhile, co
      treatment with ROS scavenger N-acetyl-L-cysteine (NAC) or H2O2 consumer catalase
      polyethylene glycol (PEG-catalase) inhibited parkin recruitment, alleviated
      autophagy formation, and mitigated JNK pathway related apoptosis. In addition,
      PINK1 silencing resulted in a lower level of autophagy, but, a higher mortality
      in HEI-OC1 cells treated with cisplatin. Taken together, data from this work
      reveal that PINK1 possesses the protective effect via induction of autophagy and
      resistance of apoptosis under cisplatin stimulus in sensory HCs and SGNs,
      implying that PINK1 might serve as an important regulator of cisplatin-elicited
      ototoxicity.

PMID- 29458151
TI  - Endoscopic Management of Pancreatobiliary Neoplasms.
AB  - Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography
      (ERCP) are the mainstays of interventional endoscopic practice. EUS occupies a
      central role in the diagnosis of pancreatobiliary neoplasms and offers a platform
      for a wide range of direct tumor therapies. Initial steps have demonstrated the
      feasibility of such applications in animal models and pilot studies. Larger
      clinical trials and incorporation of EUS-based therapies into cooperative cancer
      studies might demonstrate an impact in the clinical prognosis of patients with
      pancreatic cancer. ERCP plays an important role in elucidating indeterminate
      biliary strictures and in treating patients with malignant biliary obstruction
      who are symptomatic or have borderline-resectable or unresectable disease. ERCP
      directed ablative therapies enable neoadjuvant and palliative intervention in
      patients with malignant biliary obstruction, in particular perihilar
      cholangiocarcinoma. Additional comparative, multicenter studies are needed to
      better understand the safety and efficacy of endobiliary brachytherapy,
      photodynamic therapy, and radiofrequency ablation in patients with
      pancreatobiliary malignancies.

PMID- 29458152
TI  - Controversies in Endoscopic Eradication Therapy for Barrett's Esophagus.
AB  - Advances in endoscopic eradication therapy for Barrett's Esophagus-associated
      neoplasia have resulted in a significant paradigm shift in the diagnosis and
      management of this complex disease. A robust body of literature critically
      evaluating outcomes of resection and ablative strategies has allowed
      gastroenterologists to make quality, evidence-based decisions for their patients.
      Despite this progress, there are still many unanswered questions and challenges
      that remain. Ultimately, identification of a cost-effective screening modality,
      biomarkers for risk stratification, and strides to eliminate post surveillance
      endoscopy after endoscopic eradication therapy are essential to reach our long
      term goal for eradication of esophageal adenocarcinoma.

PMID- 29458153
TI  - EUS-Guided Transluminal Interventions.
AB  - The role of endoscopic ultrasound (EUS) has transitioned from a diagnostic to a
      therapeutic one over the past 40 years. With the advent of curvilinear array
      echoendoscopes in the 1990s with an accessory channel, multiple tools and devices
      have been developed and used for a variety of transluminal interventions. EUS
      provides a viable option and is becoming the procedure of choice for many
      interventions, including bile and pancreatic duct drainage, guiding angiotherapy,
      pancreatic fluid collection management, gallbladder drainage, and creating a
      gastrojejunostomy. Although reports demonstrate the technical success of these
      interventions, there is tremendous study heterogeneity and a relative lack of
      controlled randomized trials, which may limit our understanding of their role and
      utility. Furthermore, adverse events are relatively common and occasionally
      severe. Despite the limitations, available data strongly indicate the efficacy of
      EUS interventions when performed by well-trained endosonographers in carefully
      selected patients and managed in a multidisciplinary setting.

PMID- 29458154
TI  - The Effect of Endoscopic Surveillance in Patients With Barrett's Esophagus: A
      Systematic Review and Meta-analysis.
AB  - BACKGROUND & AIMS: Guidelines recommend endoscopic surveillance of patients with
      Barrett's esophagus (BE) to identify those with dysplasia (a precursor of
      carcinoma) or early-stage esophageal adenocarcinoma (EAC) who can be treated
      endoscopically. However, it is unclear whether surveillance increases survival
      times of patients with BE. We performed a systematic review and meta-analysis to
      qualitatively and quantitatively examine evidence for the association of
      endoscopic surveillance in patients with BE with survival and other outcomes.
      METHODS: We searched publication databases for studies reporting the effects of
      endoscopic surveillance on mortality and other EAC-related outcomes. We reviewed
      randomized controlled trials, case-control studies, studies comparing patients
      with BE who received regular surveillance with those who did not receive regular
      surveillance, and studies comparing outcomes of patients with surveillance
      detected EAC vs symptom-detected EACs. We performed a meta-analysis of
      surveillance studies to generate summary estimates using a random effects model.
      The primary aim was to examine the association of BE surveillance on EAC-related
      mortality. Secondary aims were to examine the association of BE surveillance with
      all-cause mortality and EAC stage at time of diagnosis. RESULTS: A single case
      control study did not show any association between surveillance and EAC-related
      mortality. A meta-analysis of 4 cohort studies found that lower EAC-related and
      all-cause mortality were associated with regular surveillance (relative risk,
      0.60; 95% CI, 0.50-0.71; hazard ratio, 0.75; 95% CI, 0.59-0.94). Meta-analysis of
      12 cohort studies showed lower EAC-related and all-cause mortality among patients
      with surveillance-detected EAC vs symptom-detected EAC (relative risk, 0.73; 95%
      CI, 0.57-0.94; hazard ratio, 0.59; 95% CI, 0.45-0.76). Lead- and length-time bias
      adjustment substantially attenuated/eliminated the observed benefits.
      Surveillance was associated with detection of EAC at earlier stages. A randomized
      trial is underway to evaluate the effects of endoscopic surveillance on mortality
      in patients with BE. CONCLUSIONS: In a systematic review and meta-analysis of the
      effects of surveillance in patients with BE, surveillance as currently performed
      was associated with detection of earlier-stage EAC and may provide a small
      survival benefit. However, the effects of confounding biases on these estimates
      are not fully defined and may completely or partially explain the observed
      differences between surveyed and unsurveyed patients.

PMID- 29458156
TI  - How to isolate, identify and determine antimicrobial susceptibility of anaerobic
      bacteria in routine laboratories.
AB  - BACKGROUND: There has been increased interest in the study of anaerobic bacteria
      that cause human infection during the past decade. Many new genera and species
      have been described using 16S rRNA gene sequencing of clinical isolates obtained
      from different infection sites with commercially available special culture media
      to support the growth of anaerobes. Several systems, such as anaerobic pouches,
      boxes, jars and chambers provide suitable anaerobic culture conditions to isolate
      even strict anaerobic bacteria successfully from clinical specimens. Beside the
      classical, time-consuming identification methods and automated biochemical tests,
      the use of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry has revolutionized identification of even unusual and slow-growing
      anaerobes directly from culture plates, providing the possibility of providing
      timely information about anaerobic infections. AIMS: The aim of this review
      article is to present methods for routine laboratories, which carry out anaerobic
      diagnostics on different levels. SOURCES: Relevant data from the literature
      mostly published during the last 7 years are encompassed and discussed. CONTENT:
      The review involves topics on the anaerobes that are members of the commensal
      microbiota and their role causing infection, the key requirements for collection
      and transport of specimens, processing of specimens in the laboratory, incubation
      techniques, identification and antimicrobial susceptibility testing of anaerobic
      bacteria. Advantages, drawbacks and specific benefits of the methods are
      highlighted. IMPLICATIONS: The present review aims to update and improve
      anaerobic microbiology in laboratories with optimal conditions as well as
      encourage its routine implementation in laboratories with restricted resources.

PMID- 29458157
TI  - Clostridium innocuum is a vancomycin-resistant pathogen that may cause antibiotic
      associated diarrhoea.
AB  - OBJECTIVES: Clostridium innocuum can cause extraintestinal infection in patients
      with underlying diseases. The role of C. innocuum in antibiotic-associated
      diarrhoea (AAD) remains unknown. METHODS: Clinical information of 103 patients
      from whom C. innocuum was isolated was reviewed. We carried out cellular and
      animal experiments to examine the pathogenic potential of C. innocuum in AAD.
      RESULTS: Eighty-eight per cent (91/103) of the 103 patients received antibiotics
      within 2 weeks of diarrhoea onset. Patients were further classified into two
      groups, severe colitis and diarrhoea, according to clinical severity level. The
      mortality rate was 13.6% (14/103) among the patients from whom C. innocuum was
      isolated. The lowest concentrations at which 90% of the isolates were inhibited
      for metronidazole and vancomycin were 0.5 and 16 mg/L, respectively. All isolates
      tested were susceptible to metronidazole but resistant to vancomycin. Nineteen
      randomly selected isolates (ten from severe colitis group, nine from diarrhoea
      group) were subjected to further in vitro cellular examinations. The level of
      cytotoxicity to Vero cells was significantly higher in isolates from the severe
      colitis group at both 24 and 48 hours after inoculation (24 and 48 hours, p 0.042
      and 0.033, respectively). We observed apoptotic changes that subsequently led to
      cell death in C. innocuum-infected Vero cells. Tissue damages, necrotic changes
      and oedema were observed in the mouse ileal loop infected by C. innocuum.
      CONCLUSIONS: Vancomycin-resistant C. innocuum may play a potential role as a
      causative agent of AAD. The clinical manifestations of AAD caused by C. innocuum
      were diarrhoea or severe colitis, including pseudomembranous colitis.

PMID- 29458155
TI  - Determining Risk of Colorectal Cancer and Starting Age of Screening Based on
      Lifestyle, Environmental, and Genetic Factors.
AB  - BACKGROUND & AIMS: Guidelines for initiating colorectal cancer (CRC) screening
      are based on family history but do not consider lifestyle, environmental, or
      genetic risk factors. We developed models to determine risk of CRC, based on
      lifestyle and environmental factors and genetic variants, and to identify an
      optimal age to begin screening. METHODS: We collected data from 9748 CRC cases
      and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer
      Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005.
      Half of the participants were used to develop the risk determination model and
      the other half were used to evaluate the discriminatory accuracy (validation
      set). Models of CRC risk were created based on family history, 19 lifestyle and
      environmental factors (E-score), and 63 CRC-associated single-nucleotide
      polymorphisms identified in genome-wide association studies (G-score). We
      evaluated the discriminatory accuracy of the models by calculating area under the
      receiver operating characteristic curve values, adjusting for study, age, and
      endoscopy history for the validation set. We used the models to project the 10
      year absolute risk of CRC for a given risk profile and recommend ages to begin
      screening in comparison to CRC risk for an average individual at 50 years of age,
      using external population incidence rates for non-Hispanic whites from the
      Surveillance, Epidemiology, and End Results program registry. RESULTS: In our
      models, E-score and G-score each determined risk of CRC with greater accuracy
      than family history. A model that combined both scores and family history
      estimated CRC risk with an area under the receiver operating characteristic curve
      value of 0.63 (95% confidence interval, 0.62-0.64) for men and 0.62 (95%
      confidence interval, 0.61-0.63) for women; area under the receiver operating
      characteristic curve values based on only family history ranged from 0.53 to 0.54
      and those based only E-score or G-score ranged from 0.59 to 0.60. Although
      screening is recommended to begin at age 50 years for individuals with no family
      history of CRC, starting ages calculated based on combined E-score and G-score
      differed by 12 years for men and 14 for women, for individuals with the highest
      vs the lowest 10% of risk. CONCLUSIONS: We used data from 2 large international
      consortia to develop CRC risk calculation models that included genetic and
      environmental factors along with family history. These determine risk of CRC and
      starting ages for screening with greater accuracy than the family history only
      model, which is based on the current screening guideline. These scoring systems
      might serve as a first step toward developing individualized CRC prevention
      strategies.

PMID- 29458158
TI  - Toll-like receptor 9 (TLR-9) promotor polymorphisms and gene expression are
      associated with persistent Staphylococcus aureus nasal carriage.
AB  - OBJECTIVES: Toll-like receptor (TLR) 9 could have importance in human
      Staphylococcus aureus immunity, but population-level evidence for this hypothesis
      is missing. METHODS: We phenotyped S. aureus nasal carriage of 603 volunteers
      using four consecutive swabs, genotyped TLR9 promotor variants in 106 persistent
      carriers and 219 noncarriers, measured TLR9-mRNA expression in whole blood after
      stimulation with viable S. aureus and studied mutual associations of carriage,
      transcriptional activity and single nucleotide polymorphisms while accounting for
      sex and hormone contraceptive use (HCU). RESULTS: The -1486 (rs187084) and -1237
      (rs5743836) CT haplotype was more common in noncarriers (185/438, 42%) than in
      carriers (63/212, 30%), with the TT haplotype showing a reverse association
      (noncarriers, 180/438, 41%; carriers 117/212, 55%) (chi2 p 0.001). Mean TLR9 mRNA
      expression in whole blood was higher in noncarriers (ratiocarriers/noncarriers
      0.63; 95% confidence interval, 0.43-0.92; p 0.017). A duplication of TLR9
      transcriptional activity lowered the odds of persistent S. aureus carriage by 37%
      in the overall group (odds ratio = 0.63; 95% confidence interval, 0.42-0.94; p
      0.022) and by 54% in women (odds ratio = 0.46; 95% confidence interval, 0.23
      0.90; p 0.023). Promotor haplotype and HCU had a combined effect on TLR9
      transcription (interaction model): women in the TT (risk) haplotype/HCU- stratum
      (baseline) had lower mRNA levels than women in the CT (protective) haplotype/HCU-
      (ratio 1.92; p 0.055), the CT haplotype/HCU+ (ratio 2.02; p 0.032) and the TT
      haplotype/HCU+ (ratio 2.59; p < 0.004) strata. No such associations were observed
      in men. CONCLUSIONS: We provide evidence that TLR9 affects human S. aureus
      immunity and present potential explanations for differences according to sex in
      S. aureus colonization and infection.

PMID- 29458159
TI  - Strawberry extracts efficiently counteract inflammatory stress induced by the
      endotoxin lipopolysaccharide in Human Dermal Fibroblast.
AB  - A protracted pro-inflammatory state is the common denominator in the development,
      progression and complication of the common chronic diseases. Dietary antioxidants
      represent an efficient tool to counteract this inflammatory state. The aim of the
      present work was to evaluate the effects of strawberry extracts on inflammation
      evoked by E. Coli lipopolysaccharide in Human Dermal Fibroblast, by measuring
      reactive oxygen species production, apoptosis rate, antioxidant enzymes activity,
      mitochondria functionality and also investigating the molecular pathway involved
      in inflammatory and antioxidant response. The results demonstrated that
      strawberry pre-treatment reduced intracellular reactive oxygen species levels,
      apoptotic rate, improved antioxidant defences and mitochondria functionality in
      lipopolysaccharide -treated cells. Strawberry exerted these protective activities
      through the inhibition of the NF-kB signalling pathway and the stimulation of the
      Nrf2 pathway, with a mechanism AMPK-dependent. These results confirm the health
      benefits of strawberry in the prevention of inflammation and oxidative stress
      condition in lipopolysaccharide-treated cells.

PMID- 29458160
TI  - Gambogic acid sensitizes breast cancer cells to TRAIL-induced apoptosis by
      promoting the crosstalk of extrinsic and intrinsic apoptotic signalings.
AB  - Due to the ability of tumor necrosis factor (TNF)-related apoptosis-inducing
      ligand (TRAIL) to induce cancer cell apoptosis selectively, TRAIL has attracted
      significant interest in the treatment of cancer. However, although TRAIL triggers
      apoptosis in a broad range of cancer cells, most primary cancers are often
      intrinsically TRAIL-resistant, or can acquire resistance after TRAIL treatment,
      evocating new strategies to overcome TRAIL resistance. Gambogic acid (GA), an
      active constituent of Garcinia Hanburyi (Teng Huang in Chinese), has been applied
      for thousands of years for medicinal uses, however, the potential effect of GA in
      combating cancer resistance remains poorly investigated. In this study, we found
      that GA could increase the sensitivity of breast cancer cells to TRAIL and
      enhance TRAIL-induced apoptosis. GA cooperated with TRAIL to decrease the levels
      of anti-apoptotic proteins and activate Bid (BH3 interacting-domain death
      agonist) to promote the crosstalk of extrinsic and intrinsic apoptotic signaling,
      rather than increasing the expression of TRAIL receptors DR4 and DR5. These
      findings may open a new window in the treatment of breast cancer using TRAIL in
      combination with GA.

PMID- 29458161
TI  - Multiple mycotoxin analysis in nut products: Occurrence and risk
      characterization.
AB  - Nuts consumption plays an important role in Mediterranean diet, being a good
      source of proteins, vitamins, minerals and unsaturated fatty acids. However, nuts
      can be also a source of harmful mycotoxins with negative impact on human health.
      In this work, the occurrence of 16 mycotoxins belonging to different chemical
      classes, was assessed in several nut products. The analytical method used was
      based on modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe)
      procedure followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      analysis. An extensive evaluation of different sorbents used in dispersive SPE (d
      SPE) cleanup step of QuEChERS was performed. Detection limits achieved were less
      than 3.5 MUg/kg for all the compounds and the average recoveries varied from 70
      to 91%, with relative standard deviations (RSD) <=13%. Twelve out of sixteen
      mycotoxins under study were found in the 37 nut samples analysed. Overall,
      deoxynivalenol (DON), aflatoxin-G2 (AFG2), and fusarenon-X (FUS X) were the
      compounds more commonly detected. The higher contamination value was observed in
      a cashew sample containing 336.5 MUg/kg of DON. The combination of occurrence and
      consumption data allowed to assess the exposure and characterize the associated
      risk of nut products consumption by the Portuguese population.

PMID- 29458162
TI  - Consumption and exposure assessment to sunscreen products: A key point for safety
      assessment.

PMID- 29458163
TI  - DNA adduct profiling of in vitro colonic meat digests to map red vs. white meat
      genotoxicity.
AB  - The consumption of red meat has been linked to an increased colorectal cancer
      (CRC) risk. One of the major hypotheses states that heme iron (present in red
      meat) stimulates the formation of genotoxic N-nitroso compounds (NOCs) and lipid
      peroxidation products (LPOs). By means of DNA adductomics, chemically induced DNA
      adduct formation can be mapped in relation to e.g. dietary exposures. In this
      study, this state-of-the-art methodology was used to investigate alkylation and
      (lipid per)oxidation induced DNA adduct formation in in vitro red vs. white meat
      digests. In doing so, 90 alkylation and (lipid per)oxidation induced DNA adduct
      types could be (tentatively) identified. Overall, 12 NOC- and/or LPO-related DNA
      adduct types, i.e. dimethyl-T (or ethyl-T), hydroxymethyl-T, tetramethyl-T,
      methylguanine (MeG), guanidinohydantoin, hydroxybutyl-C, hydroxymethylhydantoin,
      malondialdehyde-x3-C, O6-carboxymethylguanine, hydroxyethyl-T, carboxyethyl-T and
      3,N4-etheno-C were singled out as potential heme-rich meat digestion markers. The
      retrieval of these DNA adduct markers is in support of the heme, NOC and LPO
      hypotheses, suggesting that DNA adduct formation may indeed contribute to red
      meat related CRC risk.

PMID- 29458164
TI  - Structure-dependent induction of apoptosis by hepatotoxic pyrrolizidine alkaloids
      in the human hepatoma cell line HepaRG: Single versus repeated exposure.
AB  - Pyrrolizidine alkaloids (PA) are secondary plant compounds. PA intoxication in
      humans causes severe acute and chronic hepatotoxicity. However, the molecular
      mechanisms of PA hepatotoxicity in humans are not well understood yet. Therefore,
      we investigated cell death parameters in human HepaRG cells following either
      single (24 h) or repeated dose treatment (14 d) with structurally different PA of
      the retronecine (echimidine, senecionine), heliotridine (heliotrine), and
      otonecine type (senkirkine). After 24 h of exposure only retronecine-type PA were
      cytotoxic in HepaRG cells and induced apoptosis indicated by a loss of membrane
      asymmetry, disruption of the mitochondrial membrane potential, and increased pro
      caspase and PARP cleavage. In contrast, after 14 d all four PA exerted the
      aforementioned effects. Furthermore, the apoptotic events caspase 3, 8 and 9
      activation as well as nuclear condensation and DNA fragmentation were only
      detected for the retronecine-type PA after single exposure (6 h). Overall, our
      studies revealed a time- and structure-dependent apoptosis after PA exposure,
      suggesting that retronecine-type PA seem to be more potent apoptosis inducers
      than heliotridine- or otonecine-type PA. Furthermore, our results suggest that PA
      induced apoptosis in HepaRG cells occur most probably by involving both, the
      extrinsic death receptor pathway as well as the intrinsic mitochondrial pathway.

PMID- 29458165
TI  - A microbial identification framework for risk assessment.
AB  - Micro-organisms are increasingly used in a variety of products for commercial
      uses, including cleaning products. Such microbial-based cleaning products (MBCP)
      are represented as a more environmentally-friendly alternative to chemically
      based cleaning products. The identity of the micro-organisms formulated into
      these products is often considered confidential business information and is not
      revealed or it is only partly revealed (i.e., identification to the genus, not to
      the species). That paucity of information complicates the evaluation of the risk
      associated with their use. The accurate taxonomic identification of those micro
      organisms is important so that a suitable risk assessment of the products can be
      conducted. To alleviate difficulties associated with adequate identification of
      micro-organisms in MBCP and other products containing micro-organisms, a
      microbial identification framework for risk assessment (MIFRA) has been
      elaborated. It serves to provide guidance on a polyphasic tiered approach,
      combining the data obtained from the use of various methods (i.e., polyphasic
      approach) combined with the sequential selection of the methods (i.e., tiered) to
      achieve a satisfactory identity of the micro-organism to an acceptable taxonomic
      level. The MIFRA is suitable in various risk assessment contexts for micro
      organisms used in any commercial product.

PMID- 29458166
TI  - Statistical approach for selection of biologically informative genes.
AB  - Selection of informative genes from high dimensional gene expression data has
      emerged as an important research area in genomics. Many gene selection techniques
      have been proposed so far are either based on relevancy or redundancy measure.
      Further, the performance of these techniques has been adjudged through post
      selection classification accuracy computed through a classifier using the
      selected genes. This performance metric may be statistically sound but may not be
      biologically relevant. A statistical approach, i.e. Boot-MRMR, was proposed based
      on a composite measure of maximum relevance and minimum redundancy, which is both
      statistically sound and biologically relevant for informative gene selection. For
      comparative evaluation of the proposed approach, we developed two biological
      sufficient criteria, i.e. Gene Set Enrichment with QTL (GSEQ) and biological
      similarity score based on Gene Ontology (GO). Further, a systematic and rigorous
      evaluation of the proposed technique with 12 existing gene selection techniques
      was carried out using five gene expression datasets. This evaluation was based on
      a broad spectrum of statistically sound (e.g. subject classification) and
      biological relevant (based on QTL and GO) criteria under a multiple criteria
      decision-making framework. The performance analysis showed that the proposed
      technique selects informative genes which are more biologically relevant. The
      proposed technique is also found to be quite competitive with the existing
      techniques with respect to subject classification and computational time. Our
      results also showed that under the multiple criteria decision-making setup, the
      proposed technique is best for informative gene selection over the available
      alternatives. Based on the proposed approach, an R Package, i.e. BootMRMR has
      been developed and available at https://cran.r-project.org/web/packages/BootMRMR.
      This study will provide a practical guide to select statistical techniques for
      selecting informative genes from high dimensional expression data for breeding
      and system biology studies.

PMID- 29458167
TI  - Autosomal dominant deficiency of the interleukin-17F in recurrent aphthous
      stomatitis: Possible novel mutation in a new entity.
AB  - Recurrent Aphthous Stomatitis (RAS) is a common oral inflammatory disease with
      unknown pathogenesis. Although the immune system alterations could be involved in
      predisposition of individuals to oral candidiasis, precise etiologies of RAS have
      not been understood yet. A recent study showed that autosomal dominant IL17F
      deficiency could cause chronic mucocutaneous candidiasis. Considering the
      inflammatory nature of interleukin (IL)-17F and RAS, this study was performed to
      check any disease-associated mutation in a number of patients with RAS. Sixty-two
      Iranian individuals with RAS were investigated in this study. After DNA
      extraction using a phenol-chloroform method from the whole blood, amplification
      was accomplished by polymerase chain reaction and the products were sequenced
      using a 3730 ABI sequencer. The results of sequencing revealed a missense,
      heterozygous mutation of IL17F, converting a threonine to proline in a patient
      with RAS (T79P). The Poly-phen software suggested a damaging probability
      predicting this substitution to have a harmful effect on IL-17F protein function.
      This mutation was checked in fifty healthy individuals, and was not detected in
      any of them. This is the first study showing that a mutation in IL-17F is
      associated with susceptibility to RAS. However, functional studies and further
      studies on more patients with RAS are required to confirm such association.

PMID- 29458169
TI  - Inhibition of microsomal prostaglandin E synthase-1 facilitates liver repair
      after hepatic injury in mice.
AB  - BACKGROUND & AIMS: Liver repair following hepatic ischemia/reperfusion (I/R)
      injury is crucial to survival. This study aims to examine the role of endogenous
      prostaglandin E2 (PGE2) produced by inducible microsomal PGE synthase-1 (mPGES
      1), a terminal enzyme of PGE2 generation, in liver injury and repair following
      hepatic I/R. METHODS: mPGES-1 deficient (Ptges-/-) mice or their wild-type (WT)
      counterparts were subjected to partial hepatic ischemia followed by reperfusion.
      The role of E prostanoid receptor 4 (EP4) was then studied using a genetic
      knockout model and a selective antagonist. RESULTS: Compared with WT mice, Ptges
      /- mice exhibited reductions in alanine aminotransferase (ALT), necrotic area,
      neutrophil infiltration, chemokines, and proinflammatory cytokine levels. Ptges-/
      mice also showed promoted liver repair and increased Ly6Clow macrophages
      (Ly6Clow/CD11bhigh/F4/80high-cells) with expression of anti-inflammatory and
      reparative genes, while WT mice exhibited delayed liver repair and increased
      Ly6Chigh macrophages (Ly6Chigh/CD11bhigh/F4/80low-cells) with expression of
      proinflammatory genes. Bone marrow (BM)-derived mPGES-1-deficient macrophages
      facilitated liver repair with increases in Ly6Clow macrophages. In vitro, mPGES-1
      was expressed in macrophages polarized toward the proinflammatory profile. Mice
      treated with the mPGES-1 inhibitor Compound III displayed increased liver
      protection and repair. Hepatic I/R enhanced the hepatic expression of PGE
      receptor subtype, EP4, in WT mice, which was reduced in Ptges-/- mice. A
      selective EP4 antagonist and genetic deletion of Ptger4, which codes for EP4,
      accelerated liver repair. The proinflammatory gene expression was upregulated by
      stimulation of EP4 agonist in WT macrophages but not in EP4-deficient
      macrophages. CONCLUSIONS: These results indicate that mPGES-1 regulates
      macrophage polarization as well as liver protection and repair through EP4
      signaling during hepatic I/R. Inhibition of mPGES-1 could have therapeutic
      potential by promoting liver repair after acute liver injury. LAY SUMMARY:
      Hepatic ischemia/reperfusion injury is a serious complication that occurs in
      liver surgery. Herein, we demonstrated that inducible prostaglandin E2 synthase
      (mPGES-1), an enzyme involved in synthesizing prostaglandin E2, worsens the
      injury and delays liver repair through accumulation of proinflammatory
      macrophages. Inhibition of mPGES-1 offers a potential therapy for both liver
      protection and repair in hepatic ischemia/reperfusion injury.

PMID- 29458168
TI  - Apoptosis of enterocytes and nitration of junctional complex proteins promote
      alcohol-induced gut leakiness and liver injury.
AB  - BACKGROUND & AIMS: Binge alcohol exposure causes gut leakiness, contributing to
      increased endotoxemia and inflammatory liver injury, although the molecular
      mechanisms are still elusive. This study was aimed at investigating the roles of
      apoptosis of enterocytes and nitration followed by degradation of intestinal
      tight junction (TJ) and adherens junction (AJ) proteins in binge alcohol-induced
      gut leakiness. METHODS: The levels of intestinal (ileum) junctional complex
      proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84
      colonic cells and autopsied human ileums were determined by immunoblot,
      immunoprecipitation, immunofluorescence, and mass-spectral analyses. RESULTS:
      Binge alcohol exposure caused apoptosis of gut enterocytes with elevated serum
      endotoxin and liver injury. The levels of intestinal CYP2E1, iNOS, nitrated
      proteins and apoptosis-related marker proteins were significantly elevated in
      binge alcohol-exposed rodents. Differential, quantitative mass-spectral analyses
      of the TJ-enriched fractions of intestinal epithelial layers revealed that
      several TJ, AJ and desmosome proteins were decreased in binge alcohol-exposed
      rats compared to controls. Consistently, the levels of TJ proteins (claudin-1,
      claudin-4, occludin and zonula occludens-1), AJ proteins (beta-catenin and E
      cadherin) and desmosome plakoglobin were very low in binge alcohol-exposed rats,
      wild-type mice, and autopsied human ileums but not in Cyp2e1-null mice.
      Additionally, pretreatment with specific inhibitors of CYP2E1 and iNOS prevented
      disorganization and/or degradation of TJ proteins in alcohol-exposed T84 colonic
      cells. Furthermore, immunoprecipitation followed by immunoblot confirmed that
      intestinal TJ and AJ proteins were nitrated and degraded via ubiquitin-dependent
      proteolysis, resulting in their decreased levels. CONCLUSIONS: These results
      demonstrated for the first time the critical roles of CYP2E1, apoptosis of
      enterocytes, and nitration followed by ubiquitin-dependent proteolytic
      degradation of the junctional complex proteins, in promoting binge alcohol
      induced gut leakiness and endotoxemia, contributing to inflammatory liver
      disease. LAY SUMMARY: Binge alcohol exposure causes gut leakiness, contributing
      to increased endotoxemia and inflammatory liver injury. Our results demonstrated
      for the first time the critical roles of apoptosis of enterocytes and nitration
      followed by ubiquitin-dependent proteolytic degradation of the junctional complex
      proteins in promoting this gut leakiness and endotoxemia. These results provide
      insight into the molecular mechanisms of alcohol-induced inflammatory liver
      disease.

PMID- 29458170
TI  - Downregulation of metabotropic glutamate receptor 5 inhibits hepatoma development
      in a neurotoxin rotenone-induced Parkinson's disease model.
AB  - Clinical epidemiological studies have shown that there is a link between
      Parkinson's disease (PD) and cancer, but how PD regulates cancer development
      remains unknown. In our study, the effect of metabotropic glutamate receptor 5
      (mGlu5) on hepatoma was explored in a rotenone-induced PD model both in vitro and
      in vivo. We found that conditioned media derived from MN9D dopaminergic neuronal
      cells by rotenone-induced toxicity inhibited the growth, migration, invasion and
      promoted apoptosis of Hepa1-6 cells, which corresponded with decreased expression
      of mGlu5. Furthermore, treatment with 2-methyl-6-(phenylethynyl)pyridine (MPEP),
      a mGlu5 antagonist and knockdown of mGlu5, further reduced ATP levels and
      migration distance, and increased cleavage of caspase-3 in Hepa1-6 cells.
      Additionally, we found that conditioned media derived from rotenone-treated MN9D
      dopaminergic neuronal cells enhanced reactive oxygen species (ROS) generation and
      JNK phosphorylation, which could be further increased by MPEP treatment, and
      attenuated by mGlu5 agonist, (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG) and ROS
      scavenger, N-acetyl-l-cysteine (NAC). The results indicated that down-regulation
      of mGlu5 promoted cell apoptosis through the intracellular ROS/JNK signaling
      pathway in a rotenone-induced cellular PD model. These findings were confirmed in
      vivo in a rotenone-induced rat model of PD combined with diethylnitrosamine (DEN)
      induced hepatoma. Expression of Ki67 was decreased, and the levels of caspase-3
      and p-JNK were increased in this model, which was accompanied by a decrease in
      protein expression of mGlu5. The study suggest that negative regulation of mGlu5
      may inhibit hepatoma development in a rotenone-induced PD model, and as such may
      help with our further understanding of the correlation between PD and cancer.

PMID- 29458171
TI  - Toxicology studies of furosine in vitro/in vivo and exploration of the related
      mechanism.
AB  - AIM: Furosine is one of the Maillard reaction products (MRPs) and is found in a
      variety of heat-processed food. Yet its toxicity is still unclear. The present
      study was designed to assess furosine toxicity in cell models and in CD-1 mice,
      respectively. METHODS: In vitro, the effects of furosine on the cell viability,
      cell cycle and apoptosis (Hek293, HepG2, SK-N-SH and Caco2) were detected and
      evaluated, sensitive cell lines and proper dosage of furosine for further animal
      experiment were determined, and the mechanisms of toxicity were explored. In
      vivo, the acute toxicity studieswere performed, organ index, hematology
      parameters, functions of liver/kidney and pathological changes were detected and
      the target organs were uncovered. RESULTS: Hek293 cells and HepG2 cells were
      themost sensitive to furosine with respect to cytotoxicity and apoptosis.
      Furosine inhibited mice weight gain, and affected the functions of liver and
      kidney. CONCLUSIONS: Furosine posed toxic effects on mice liver and kidney,
      suggested thatthey were the target organs for furosine toxicity. This study for
      the first time provides evidence that high dosages of furosine pose adverse
      biological effects on the health of animals through induction of cell apoptosis
      and activation of inflammatory necrosis response.

PMID- 29458172
TI  - Modelling human myoblasts survival upon xenotransplantation into immunodeficient
      mouse muscle.
AB  - Cell transplantation has been challenged in several clinical indications of
      genetic or acquired muscular diseases, but therapeutic success were mitigated. To
      understand and improve the yields of tissue regeneration, we aimed at modelling
      the fate of CD56-positive human myoblasts after transplantation. Using
      immunodeficient severe combined immunodeficiency (SCID) mice as recipients, we
      assessed the survival, integration and satellite cell niche occupancy of human
      myoblasts by a triple immunohistochemical labelling of laminin, dystrophin and
      human lamin A/C. The counts were integrated into a classical mathematical decline
      equation. After injection, human cells were essentially located in the
      endomysium, then they disappeared progressively from D0 to D28. The final number
      of integrated human nuclei was grossly determined at D2 after injection,
      suggesting that no more efficient fusion between donor myoblasts and host fibers
      occurs after the resolution of the local damages created by needle insertion.
      Almost 1% of implanted human cells occupied a satellite-like cell niche. Our
      mathematical model validated by histological counting provided a reliable
      quantitative estimate of human myoblast survival and/or incorporation into SCID
      muscle fibers. Informations brought by histological labelling and this
      mathematical model are complementary.

PMID- 29458173
TI  - Deregulation of Nrf2/ARE signaling pathway causes susceptibility of dystrophin
      deficient myotubes to menadione-induced oxidative stress.
AB  - Duchenne muscular dystrophy (DMD) is an X chromosome-linked disorder caused by a
      mutation in the dystrophin gene. Many previous studies reported that the skeletal
      muscles of DMD patients were more susceptible to oxidative stress than those of
      healthy people. However, not much has been known about the responsible mechanism
      of the differential susceptibility. In this study, we established dystrophin
      knock-down (DysKD) cell lines by transfection of dystrophin shRNA lentiviral
      particles into C2 cells and found that DysKD myotubes are more vulnerable to
      menadione-induced oxidative stress than control myotubes. We focused on the
      nuclear erythroid 2-related factor 2 (Nrf2) which is a transcription factor that
      regulates the expression of phase II antioxidant enzymes by binding to the
      antioxidant response element (ARE). Under menadione-induced oxidative stress, the
      translocation of Nrf2 to the nucleus is significantly decreased in the DysKD
      myotubes. In addition, the binding of Nrf2 to ARE site of Bcl-2 gene as well as
      protein expression of Bcl-2 is decreased compared to the control cells.
      Interestingly, sulforaphane increased Akt activation and Nrf2 translocation to
      the nucleus in the DysKD myotubes. These results suggest that the Nrf2 pathway
      might be the responsible pathway to the oxidative stress-induced muscle damage in
      DMD.

PMID- 29458175
TI  - Maintenance of hematopoietic stem and progenitor cells in fetal intra-aortic
      hematopoietic clusters by the Sox17-Notch1-Hes1 axis.
AB  - The aorta-gonad-mesonephros region, from which definitive hematopoiesis first
      arises in midgestation mouse embryos, has intra-aortic hematopoietic clusters
      (IAHCs) containing hematopoietic stem cells (HSCs) and hematopoietic progenitor
      cells (HPCs). We previously reported expression of the transcription factor Sox17
      in IAHCs, and overexpression of Sox17 in CD45lowc-KIThigh cells comprising IAHCs
      maintains the formation of cell clusters and their multipotency in vitro over
      multiple passages. Here, we demonstrate the importance of NOTCH1 in IAHC
      formation and maintenance of the HSC/HPC phenotype. We further show that Notch1
      expression is positively regulated by SOX17 via direct binding to its gene
      promoter. SOX17 and NOTCH1 were both found to be expressed in vivo in cells of
      IAHCs by whole mount immunostaining. We found that cells transduced with the
      active form of NOTCH1 or its downstream target, Hes1, maintained their
      multipotent colony-forming capacity in semisolid medium. Moreover, cells
      stimulated by NOTCH1 ligand, Jagged1, or Delta-like protein 1, had the capacity
      to form multilineage colonies. Conversely, knockdown of Notch1 and Hes1 led to a
      reduction of their multipotent colony-forming capacity. These results suggest
      that the Sox17-Notch1-Hes1 pathway is critical for maintaining the
      undifferentiated state of IAHCs.

PMID- 29458174
TI  - Networks that link cytoskeletal regulators and diaphragm proteins underpin
      filtration function in Drosophila nephrocytes.
AB  - Insect nephrocytes provide a valuable model for kidney disease, as they are
      structurally and functionally homologous to mammalian kidney podocytes. They
      possess an exceptional macromolecular assembly, the nephrocyte diaphragm (ND),
      which serves as a filtration barrier and helps maintain tissue homeostasis by
      filtering out wastes and toxic products. However, the elements that maintain
      nephrocyte architecture and the ND are not understood. We show that Drosophila
      nephrocytes have a unique cytoplasmic cluster of F-actin, which is maintained by
      the microtubule cytoskeleton and Rho-GTPases. A balance of Rac1 and Cdc42
      activity as well as proper microtubule organization and endoplasmic reticulum
      structure, are required to position the actin cluster. Further, ND proteins Sns
      and Duf also localize to this cluster and regulate organization of the actin and
      microtubule cytoskeleton. Perturbation of any of these inter-dependent components
      impairs nephrocyte ultrafiltration. Thus cytoskeletal components, Rho-GTPases and
      ND proteins work in concert to maintain the specialized nephrocyte architecture
      and function.

PMID- 29458176
TI  - GRP78 Promotes Hepatocellular Carcinoma proliferation by increasing FAT10
      expression through the NF-kappaB pathway.
AB  - Glucose-regulated protein 78(GRP78) and the ubiquitin-like protein FAT10 each
      promote proliferation in hepatocellular carcinoma(HCC). However, the relationship
      of GRP78 and FAT10 in HCC proliferation are still not known. In this study, we
      found that GRP78 and FAT10 were significantly overexpressed in HCC tissues
      compare with adjacent non-cancerous tissues, and a positive correlation was found
      between their expression and associated proliferation characteristics. High
      expression of GRP78 and FAT10 were positively correlated with tumor proliferation
      and poor prognosis in HCC. Moreover, GRP78 knockdown reduced FAT10 expression and
      suppressed HCC proliferation in vitro and in vivo. The effects of GRP78 knockdown
      were rescued by FAT10 up-regulation, whereas FAT10 knockdown reduced HCC
      proliferation enhanced by GRP78 up-regulation. Furthermore, GRP78 modulated FAT10
      expression by regulating the NF-kappaB pathway, direct activation of the NF
      kappaB pathway increased the expression of FAT10, a gene counteracting the tumor
      suppressor p53. Taken together, these results suggest that this newly identified
      GRP78-NF-kappaB-FAT10 axis will provide novel insight into the understanding of
      the regulatory mechanisms of proliferation in human HCC.

PMID- 29458177
TI  - Colorimetric detection of microRNA based on DNAzyme and nuclease-assisted
      catalytic hairpin assembly signal amplification.
AB  - Accurate and quantitative analysis of microRNA (miRNA) expression is critical for
      the diagnostics and theranostics of a disease. Herein, a proof-of-concept of a
      colorimetric horseradish peroxidase-mimicking DNAzyme (HRP-DNAzyme) biosensor for
      miRNA assay based on nuclease-assisted catalytic hairpin assembly (CHA) signal
      amplification was demonstrated. Duplex-specific nuclease (DSN) was employed to
      cleave the single-stranded DNA (ssDNA) chimeric probe (CP) on the magnetic bead
      (MB) surface via hybridization of the CP and target miRNA. The regenerated miRNA
      can cleave a large number of ssDNA CP to produce CHA initiator sequence
      fragments. The CP consists of two main regions: a target miRNA recognition DNA
      sequence at the 5' end and a CHA initiator (CI) sequence at the 3' end. The
      catalyzed assembly process of CHA produces a large amount of G-rich DNA. In the
      presence of hemin, the G-rich DNA forms G-quadruplex/hemin complex and mimics the
      horseradish peroxidase activity, which catalyzes a colorimetric reaction. For the
      proof-of-concept, microRNA-21 (miR-21) was selected as the model target to
      authenticate this strategy as a versatile assay platform. The proposed strategy
      allowed quantitation of the sequence specificity of miRNA-21 with a detection
      limit of 9.2 fM in a dynamic range from 10 fM-1 nM, with an excellent ability to
      discriminate the differences in miRNAs. Additionally, the miRNA assay in real
      samples was satisfactory, thereby confirming its applicability. Therefore, this
      method exhibited a great potential as a miRNA quantification method in biomedical
      research and clinical diagnosis.

PMID- 29458178
TI  - Direct Convergence of Light and Auxin Signaling Pathways in Arabidopsis.

PMID- 29458179
TI  - Live and Let Die: The Core Circadian Oscillator Coordinates Plant Life History
      and Pilots Leaf Senescence.

PMID- 29458180
TI  - Feature-guided attentional capture cannot be prevented by spatial filtering.
AB  - Feature-based control processes guide attention towards objects with target
      features in visual search. While these processes are assumed to operate globally
      across the entire visual field, it remains controversial whether target-matching
      objects at task-irrelevant locations can be excluded from attentional selection,
      especially when spatial attention is already narrowly focused elsewhere. We
      investigated whether probe stimuli at irrelevant lateral locations capture
      attention when they precede search displays where targets are defined either by a
      specific feature (colour or orientation) or by a colour/orientation conjunction
      by measuring N2pc components (an electrophysiological marker of attentional
      target selection) to these probes. Reliable N2pcs were triggered by probes not
      only in the feature search tasks but also when participants searched for feature
      conjunctions, in spite of the fact that conjunction search requires focal spatial
      attention. Analogous N2pc results were found in the absence of any spatial
      uncertainty about the location of conjunctively defined targets, which always
      appeared at fixation. These results show that rapid attentional capture by
      objects with target-matching features cannot be prevented by top-down spatial
      filtering mechanisms, and confirm that feature-based attentional guidance
      processes operate in a spatially global fashion.

PMID- 29458181
TI  - Hospitalization burden associated with malignant neoplasia and in situ carcinoma
      in vulva and vagina during a 5-year period (2009-2013) in Spain: An
      epidemiological study.
AB  - BACKGROUND: Vulvar and vaginal cancers are considered rare cancers in women.
      Human Papillomavirus is responsible for 30-76% of them. The aim of this study was
      to describe the burden of hospital admissions by malignant neoplasia (MN) and in
      situ carcinoma (ISC) of vulva and vagina from 2009 to 2013, in Spain METHODS:
      This observational, descriptive study used discharge information obtained from
      the national surveillance system for hospital data, Conjunto Minimo Basico de
      Datos, CMBD, provided by the Ministry of Health. RESULTS: From 2009-2013, we
      found 9,896 hospitalizations coded as MN or ISC of vulva and vagina. Mean age of
      hospitalization was 69.94 +/- 15.16 years; average length of hospital stay (ALOS)
      was 10.02 +/- 12.40 days, and mean hospitalization costs were 5,140.31 +/-
      3,220.61 euros. Mean hospitalization rate was 9.874 per 100,000 women aged >14
      years old (95% CI: 9.689-10.058); mean mortality rate was 0.932 per 100,000 women
      aged >14 years old (95% CI: 0.872-0.991) and mean case fatality rate was 9.438%
      (95% CI: 8.862-10.014). CONCLUSION: MN and ISC of vulva and vagina are
      responsible for a considerable hospitalization burden. Information about these
      hospitalizations could be useful for cost effectiveness analysis and monitoring
      of HPV vaccination effectiveness.

PMID- 29458182
TI  - A direct gateway into the extracellular space: Unconventional secretion of FGF2
      through self-sustained plasma membrane pores.
AB  - As illustrated by a diverse set of examples in this special issue, multiple
      mechanisms of protein secretion have been identified in eukaryotes that do not
      involve the endoplasmic reticulum (ER) and the Golgi apparatus. Here we focus on
      the type I pathway with Fibroblast Growth Factor 2 (FGF2) being the most
      prominent example. Unconventional secretion of FGF2 from cells is mediated by
      direct protein translocation across the plasma membrane. A unique feature of this
      process is the ability of FGF2 to form its own membrane translocation
      intermediate through oligomerization and membrane insertion. This process depends
      on the phosphoinositide PI(4,5)P2 at the inner leaflet and results in the
      formation of lipidic membrane pores in the plasma membrane. Various lines of
      evidence suggest that these pores are characterized by a toroidal architecture
      with FGF2 oligomers being accommodated in the center of these structures. At the
      outer leaflet of the plasma membrane, membrane proximal heparan sulfate
      proteoglycans are required for the final step of FGF2 translocation into the
      extracellular space. Based upon mutually exclusive interactions of FGF2 with
      PI(4,5)P2 versus heparan sulfates, an assembly/disassembly pathway has been
      proposed to be the underlying principle of directional transport of FGF2 across
      the plasma membrane. Thus, the core mechanism of unconventional secretion of FGF2
      is based upon three discrete steps with (i) PI(4,5)P2 dependent oligomerization
      of FGF2 at the inner leaflet, (ii) insertion of membrane spanning FGF2 oligomers
      into the plasma membrane and (iii) disassembly at the outer leaflet mediated by
      heparan sulfates that subsequently retain FGF2 on cell surfaces. This process has
      recently been reconstituted with an inside-out membrane model system using giant
      unilamellar vesicles providing a compelling explanation of how FGF2 reaches the
      extracellular space in an ER/Golgi independent manner. This review is part of a
      Special Issue of SCDB on "unconventional protein secretion" edited by Walter
      Nickel and Catherine Rabouille.

PMID- 29458183
TI  - Age-Dependent Attitudes of Ischemic Patients Toward Disability After
      Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Infarction.
AB  - OBJECTIVE: To investigate patient attitudes toward acceptable levels of
      disability after decompressive surgery for malignant middle cerebral artery
      infarction, including impact of patient age, to improve process of surgical
      informed consent. METHODS: Patients who had experienced a recent minor stroke
      were asked to complete a questionnaire containing 2 parts: demographic
      information, including patient age, sex, years of education, working status,
      religion, and economic status, and acceptable level of disability based on
      modified Rankin Scale (mRS) with corresponding illustrations to explain mRS
      levels. RESULTS: Patient age was identified as an independent determinant of the
      worst acceptable mRS score with a negative correlation. For nondominant
      hemispheric malignant infarction, the worst acceptable mRS score was
      significantly lower (mean +/- SD 2.0 +/- 1.3) for the oldest patients (>70 years
      old) compared with patients <60 years old (mean +/- SD 3.0 +/- 0.6) and 60-70
      years old (mean +/- SD 3.0 +/- 0.8). For dominant hemispheric malignant
      infarction with language impairment, all age groups showed a significantly lower
      value for worst acceptable mRS score (mean +/- SD 1.8 +/- 1.1 for patients <60
      years old, 1.8 +/- 1.2 for patients 60-70 years old, and 1.0 +/- 1.4 for patients
      >70 years old). CONCLUSIONS: Patients showed different attitudes toward
      disability according to their age. Patients >70 years old showed the lowest worst
      acceptable mRS score after surgical treatment of malignant infarction. Language
      impairment with dominant hemispheric infarction further decreased the worst
      acceptable mRS score.

PMID- 29458184
TI  - DEFUSE-3 Trial: Reinforcing Evidence for Extended Endovascular Intervention Time
      Window for Ischemic Stroke.

PMID- 29458185
TI  - Tiny Cerebral Aneurysms Can Be Treated Safely and Effectively with Low-Profile
      Visualized Intraluminal Support Stent-Assisted Coiling or Coiling Alone.
AB  - BACKGROUND: The effectiveness and safety of LVIS stent-coiling is currently not
      known for treating tiny intracranial aneurysms. OBJECTIVE: To investigate the
      effectiveness and safety of Low-profile visualized intraluminal support (LVIS)
      stent-assisted coiling and coiling alone in treating patients with mostly
      ruptured tiny aneurysms. METHODS: Seventy-five patients with tiny intracranial
      aneurysms, including 63 ruptured ones, were treated endovascularly and analyzed.
      RESULTS: In the coiling group, complete occlusion was achieved in 35 patients
      (83.6%)-nearly complete in 4 patients (9.5%) and noncomplete in 3 patients
      (7.1%). Intraprocedural rerupture occurred in 2 patients (4.8%), and coil
      protrusion occurred in 1 patient, with a complication rate of 7.1%. Clinical
      follow-up at 6-12 months revealed a modified Rankin Scale (mRS) score of 0-1 in
      41 patients and 3 in 1 patient. In the stent-assisted group, occlusion was
      complete in 12 patients (36.4%), nearly complete in 15 patients (45.5%), and
      noncomplete in 6 patients (18.1%). Six stents (18.2%) did not have good adherence
      to the wall, with thrombus formation in 3 stents (9.1%). Follow-up angiography in
      27 patients at 3-6 months showed no dislocation of the stents, complete occlusion
      in 24 patients (88.9%), and nearly complete occlusion in the other 3 patients. At
      6 months, the mRS score was 0 in 30 patients and 2 in 3 patients. No significant
      (P > 0.05) differences existed between the 2 groups. CONCLUSION: Tiny cerebral
      aneurysms can be safely and effectively treated with appropriate endovascular
      approaches based on aneurysm specific morphology, especially neck size and neck
      to-dome ratio.

PMID- 29458186
TI  - Understanding the Functional Neuroanatomical Basis of Meditation for Improving
      Patient Wellness and Outcomes.

PMID- 29458188
TI  - Robust is not necessarily reliable: From within-subjects fMRI contrasts to
      between-subjects comparisons.
AB  - Advances in cognitive and affective neuroscience come largely from within
      subjects comparisons, in which the functional significance of neural activity is
      determined by contrasting two or more experimental conditions. Clinical and
      social neuroscience studies have attempted to leverage between-subject
      variability in such condition differences to better understand psychopathology
      and other individual differences. Shifting from within-to between-subjects
      comparisons requires that measures have adequate internal consistency to function
      as individual difference variables. This is particularly relevant for difference
      scores-which have lower reliability. The field has assumed reasonable internal
      consistency of neural measures based on consistent findings across studies (i.e.,
      if a within-subject difference in neural activity is robust, then it must be
      reliable). Using one of the most common fMRI paradigms in the clinical
      neuroscience literature (i.e., a face- and shape-matching task), in a large
      sample of adolescents (N = 139) we replicate a robust finding: amygdala
      activation is greater for faces than shapes. Moreover, we demonstrate that the
      internal consistency of the amygdala in face and shape blocks was excellent
      (Spearman-Brown corrected reliability [SB] > .94). However, the internal
      consistency of the activation difference between faces and shapes was nearly zero
      (SB = -.06). This reflected the fact that the amygdala response to faces and
      shapes was highly correlated (r = .97) across individuals. Increased neural
      activation to faces versus shapes could not possibly function as an individual
      difference measure in these data-illustrating how neural activation can be robust
      within subjects, but unreliable as an individual difference measure. Strong and
      reproducible condition differences in neural activity are not necessarily well
      suited for individual differences research-and neuroimaging studies should always
      report the internal consistency of, and correlations between, activations used in
      individual differences research.

PMID- 29458189
TI  - Impact of time-of-day on diffusivity measures of brain tissue derived from
      diffusion tensor imaging.
AB  - Diurnal fluctuations in MRI measures of structural and functional properties of
      the brain have been reported recently. These fluctuations may have a
      physiological origin, since they have been detected using different MRI
      modalities, and cannot be explained by factors that are typically known to
      confound MRI measures. While preliminary evidence suggests that measures of
      structural properties of the brain based on diffusion tensor imaging (DTI)
      fluctuate as a function of time-of-day (TOD), the underlying mechanism has not
      been investigated. Here, we used a longitudinal within-subjects design to
      investigate the impact of time-of-day on DTI measures. In addition to using the
      conventional monoexponential tensor model to assess TOD-related fluctuations, we
      used a dual compartment tensor model that allowed us to directly assess if any
      change in DTI measures is due to an increase in CSF/free-water volume fraction or
      due to an increase in water diffusivity within the parenchyma. Our results show
      that Trace or mean diffusivity, as measured using the conventional
      monoexponential tensor model tends to increase systematically from morning to
      afternoon scans at the interface of grey matter/CSF, most prominently in the
      major fissures and the sulci of the brain. Interestingly, in a recent study of
      the glymphatic system, these same regions were found to show late enhancement
      after intrathecal injection of a CSF contrast agent. The increase in Trace also
      impacts DTI measures of diffusivity such as radial and axial diffusivity, but
      does not affect fractional anisotropy. The dual compartment analysis revealed
      that the increase in diffusivity measures from PM to AM was driven by an increase
      in the volume fraction of CSF-like free-water. Taken together, our findings
      provide important insight into the likely physiological origins of diurnal
      fluctuations in MRI measurements of structural properties of the brain.

PMID- 29458190
TI  - Cannabinoids prevent depressive-like symptoms and alterations in BDNF expression
      in a rat model of PTSD.
AB  - Posttraumatic stress disorder (PTSD) is a debilitating condition highly comorbid
      with depression. The endocannabinoid (eCB) system and brain-derived neurotrophic
      factor (BDNF) are suggestively involved in both disorders. We examined whether
      cannabinoids can prevent the long-term depressive-like symptoms induced by
      exposure to the shock and situational reminders (SRs) model of PTSD. The CB1/2
      receptor agonist WIN55,212-2 (0.5 mg/kg; i.p.), the fatty acid hydrolase (FAAH)
      inhibitor URB597 (0.3 mg/kg, i.p.) or vehicle were administered 2 h after severe
      shock. Cannabinoids prevented the shock/SRs-induced alterations in social
      recognition memory, locomotion, passive coping, anxiety-like behavior, anhedonia,
      fear retrieval, fear extinction and startle response as well as the decrease in
      BDNF levels in the hippocampus and prefrontal cortex (PFC). Furthermore,
      significant correlations were found between depressive-like behaviors and BDNF
      levels in the brain. The findings suggest that cannabinoids may prevent both
      depressive- and PTSD-like symptoms following exposure to severe stress and that
      alterations in BDNF levels in the brains' fear circuit are involved in these
      effects.

PMID- 29458191
TI  - A novel neuropilin-1-binding sequence in the human T-cell lymphotropic virus type
      1 envelope glycoprotein.
AB  - Entry of human T-cell lymphotropic virus type 1 (HTLV-1) into host cells is
      mainly mediated by interactions between the viral envelope glycoprotein surface
      unit (SU) and three host receptors: glucose transporter type 1, heparin/heparan
      sulfate proteoglycan, and neuropilin-1 (Nrp1). Here, we analyzed the interaction
      between HTLV-1 SU and Nrp1 using nuclear magnetic resonance and isothermal
      titration calorimetry. We found that two SU peptides, residues 85-94 and residues
      304-312, bound directly to the Nrp1 b1 domain with affinities of 7.4 and 17.7
      MUM, respectively. The binding modes of both peptides were almost identical to
      those observed for Tuftsin and vascular endothelial growth factor A binding to
      the Nrp1 b1 domain. These results suggest that the C-terminal region of HTLV-1 SU
      contains a novel site for direct binding of virus to the Nrp1 b1 domain. Our
      biophysical characterization of the SU peptides may help in developing inhibitors
      of HTLV-1 entry.

PMID- 29458187
TI  - MRI techniques to measure arterial and venous cerebral blood volume.
AB  - The measurement of cerebral blood volume (CBV) has been the topic of numerous
      neuroimaging studies. To date, however, most in vivo imaging approaches can only
      measure CBV summed over all types of blood vessels, including arterial, capillary
      and venous vessels in the microvasculature (i.e. total CBV or CBVtot). As
      different types of blood vessels have intrinsically different anatomy, function
      and physiology, the ability to quantify CBV in different segments of the
      microvascular tree may furnish information that is not obtainable from CBVtot,
      and may provide a more sensitive and specific measure for the underlying
      physiology. This review attempts to summarize major efforts in the development of
      MRI techniques to measure arterial (CBVa) and venous CBV (CBVv) separately.
      Advantages and disadvantages of each type of method are discussed. Applications
      of some of the methods in the investigation of flow-volume coupling in healthy
      brains, and in the detection of pathophysiological abnormalities in brain
      diseases such as arterial steno-occlusive disease, brain tumors, schizophrenia,
      Huntington's disease, Alzheimer's disease, and hypertension are demonstrated. We
      believe that the continual development of MRI approaches for the measurement of
      compartment-specific CBV will likely provide essential imaging tools for the
      advancement and refinement of our knowledge on the exquisite details of the
      microvasculature in healthy and diseased brains.

PMID- 29458192
TI  - Magnetic resonance imaging safety in nonconditional pacemaker and defibrillator
      recipients: A meta-analysis and systematic review.
AB  - BACKGROUND: Recommendations regarding performance of magnetic resonance imaging
      (MRI) in non-MRI conditional pacemaker and defibrillator recipients are evolving.
      Previous studies have suggested low adverse event rates with MRI in
      nonconditional cardiac implantable electronic device (CIED) recipients, but low
      power limits optimal characterization of risk. OBJECTIVE: The purpose of this
      study was to perform a systematic review and meta-analysis to characterize the
      clinical risk associated with MRI in CIED recipients in order to improve power.
      METHODS: PubMed and CINAHL indexed articles from 1990 to 2017 were queried. A
      random effects model was used for meta-analysis of continuous variables. Safety
      outcomes were evaluated with descriptive statistics. RESULTS: Seventy studies of
      non-MRI conditional devices undergoing MRI were identified, allowing for analysis
      of 5099 patients who underwent a total of 5908 MRI studies. Heterogeneity in lead
      parameter changes was observed within studies, although smaller variances were
      noted between studies. All lead characteristics and battery voltages showed very
      small, clinically insignificant changes when assessed as a pooled cohort,
      although cases of clinically relevant outcomes were also noted (lead failure 3,
      implantable cardioverter-defibrillator shock 1, electrical reset 94). Electrical
      resets were found only in older devices. Defibrillator function was unchanged,
      and inappropriate shocks were avoided with pre-MRI programming changes.
      CONCLUSION: This review demonstrated low lead failure and clinical event rates in
      non-MRI conditional pacemaker and defibrillator recipients undergoing MRI.
      Observed changes were small and interstudy variance was low, suggesting that the
      composite event rates offer a reasonable estimate of true effect. The observed
      adverse events reinforce the need for ongoing vigilance and caution, particularly
      with older devices.

PMID- 29458193
TI  - Attenuation of neuro-inflammation improves survival and neurodegeneration in a
      mouse model of severe neonatal hyperbilirubinemia.
AB  - All pre-term newborns and a high proportion of term newborns develop neonatal
      jaundice. Neonatal jaundice is usually a benign condition and self-resolves
      within few days after birth. However, a combination of unfavorable complications
      may lead to acute hyperbilirubinemia. Excessive hyperbilirubinemia may be toxic
      for the developing nervous system leading to severe neurological damage and death
      by kernicterus. Survivors show irreversible neurological deficits such as motor,
      sensitive and cognitive abnormalities. Current therapies rely on the use of
      phototherapy and, in unresponsive cases, exchange transfusion, which is performed
      only in specialized centers. During bilirubin-induced neurotoxicity different
      molecular pathways are activated, ranging from oxidative stress to endoplasmic
      reticulum (ER) stress response and inflammation, but the contribution of each
      pathway in the development of the disease still requires further investigation.
      Thus, to increase our understanding of the pathophysiology of bilirubin
      neurotoxicity, encephalopathy and kernicterus, we pharmacologically modulated
      neurodegeneration and neuroinflammation in a lethal mouse model of neonatal
      hyperbilirubinemia. Treatment of mutant mice with minocycline, a second
      generation tetracycline with anti-inflammatory and neuroprotective properties,
      resulted in a dose-dependent rescue of lethality, due to reduction of
      neurodegeneration and neuroinflammation, without affecting plasma bilirubin
      levels. In particular, rescued mice showed normal motor-coordination capabilities
      and behavior, as determined by the accelerating rotarod and open field tests,
      respectively. From the molecular point of view, rescued mice showed a dose
      dependent reduction in apoptosis of cerebellar neurons and improvement of
      dendritic arborization of Purkinje cells. Moreover, we observed a decrease of
      bilirubin-induced M1 microglia activation at the sites of damage with a reduction
      in oxidative and ER stress markers in these cells. Collectively, these data
      indicate that neurodegeneration and neuro-inflammation are key factors of
      bilirubin-induced neonatal lethality and neuro-behavioral abnormalities. We
      propose that the application of pharmacological treatments having anti
      inflammatory and neuroprotective effects, to be used in combination with the
      current treatments, may significantly improve the management of acute neonatal
      hyperbilirubinemia, protecting from bilirubin-induced neurological damage and
      death.

PMID- 29458195
TI  - Human dorsal root ganglion pulsed radiofrequency treatment modulates
      cerebrospinal fluid lymphocytes and neuroinflammatory markers in chronic
      radicular pain.
AB  - Radicular pain is a common cause of disability. Traditionally treatment has been
      either epidural steroid injection providing short-term relief or surgery with
      associated complications. Pulsed radiofrequency (PRF) applied to the dorsal root
      ganglion (DRG) is a minimally invasive day-care treatment, which is gaining
      significant clinical acceptance in a selective group of patients with pure
      radicular pain. Greater insights into the immunomodulatory effects of this
      procedure may help to further optimise its application and find alternative
      treatment options. We have examined it's effect on lymphocyte frequencies and
      secreted inflammatory markers in the cerebrospinal fluid (CSF) and correlated
      this with clinical outcome to identify clinical markers of chronic radicular
      pain. Ten patients were recruited for the study. CSF lymphocyte frequencies and
      levels of cytokines, chemokines and growth factors were quantified using flow
      cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Clinical
      assessment utilised Brief Pain Inventory scores. Nine out of ten patients (90%)
      demonstrated significant reduction in pain severity (p = 0.0007) and pain
      interference scores (p = 0.0015) three months post-treatment. Our data revealed
      significant reductions in CD56+, CD3-, NK cell frequencies (p = 0.03) and IFN
      gamma levels (p = 0.03) in treatment responders, while CD8+ T cell frequencies (p
      = 0.02) and IL-6 levels were increased (p = 0.05). IL-17 inversely correlated
      with post-treatment pain severity score (p = 0.01) and pre and post-treatment
      pain interference scores (p = 0.03, p = 0.01). These results support the concept
      that chronic radicular pain is a centrally mediated neuroimmune phenomenon and
      the mechanism of action of DRG PRF treatment is immunomodulatory.

PMID- 29458194
TI  - Differential effects of acute versus chronic stress on ethanol sensitivity:
      Evidence for interactions on both behavioral and neuroimmune outcomes.
AB  - Acute alcohol intoxication induces significant alterations in brain cytokines.
      Since stress challenges also profoundly impact central cytokine expression, these
      experiments examined the influence of acute and chronic stress on ethanol-induced
      brain cytokine responses. In Experiment 1, adult male rats were exposed to acute
      footshock. After a post-stress recovery interval of 0, 2, 4, or 24 h, rats were
      administered ethanol (4 g/kg; intragastric), with trunk blood and brains
      collected 3 h later. In non-stressed controls, acute ethanol increased expression
      of Il-6 and IkappaBalpha in the hippocampus. In contrast, rats exposed to
      footshock 24 h prior to ethanol demonstrated potentiation of hippocampal Il-6 and
      IkappaBalpha expression relative to ethanol-exposed non-stressed controls.
      Experiment 2 subsequently examined the effects of chronic stress on ethanol
      related cytokine expression. Following a novel chronic escalating stress
      procedure, rats were intubated with ethanol. As expected, acute ethanol increased
      Il-6 expression in all structures examined, yet the Il-6 response was attenuated
      exclusively in the hippocampus in chronically stressed rats. Later experiments
      determined that neither acute nor chronic stress affected ethanol
      pharmacokinetics. When ethanol hypnosis was examined, however, rats exposed to
      chronic stress awoke at significantly lower blood ethanol levels compared to
      acutely stressed rats, despite similar durations of ethanol-induced sedation.
      These data indicate that chronic stress may increase sensitivity to ethanol
      hypnosis. Together, these experiments demonstrate an intriguing interaction
      between recent stress history and ethanol-induced increases in hippocampal Il-6,
      and may provide insight into novel pharmacotherapeutic targets for prevention and
      treatment of alcohol-related health outcomes based on stress susceptibility.

PMID- 29458196
TI  - Within-subject associations between inflammation and features of depression:
      Using the flu vaccine as a mild inflammatory stimulus.
AB  - BACKGROUND: Inflammation plays a role in mood and behavior that may be relevant
      to identifying risk factors and treatment for depression and other stress-related
      illnesses. The purpose of this study was to examine whether fluctuations in
      inflammation following a mild immune stimulus were associated with changes in
      daily reported features of depression for up to a week in a healthy sample of
      young adults. METHODS: Forty-one undergraduate students completed daily diaries
      of mood, feelings of social disconnection, sleep, and physical symptoms for one
      week before and after receiving the seasonal influenza vaccine. Circulating
      plasma interleukin-6 (IL-6) was measured via blood samples taken immediately
      before and one day after vaccination. RESULTS: There was a significant increase
      in circulating IL-6 from pre- to post-intervention (p = .008), and there was
      significant variability in the magnitude of IL-6 change. Greater increases in IL
      6 were associated with greater mood disturbance on post-vaccine days,
      specifically depressed mood and cognitive symptoms. CONCLUSIONS: Minor increases
      in inflammation were associated with corresponding increases in features of
      depression, and these associations occurred in the absence of any physical
      symptoms. The influenza vaccine could be used to probe causal relationships with
      a high degree of ecological validity, even in high-risk and vulnerable
      populations, to better understand the role of inflammation in the pathogenesis of
      depression.

PMID- 29458198
TI  - Adverse childhood experiences and adult inflammation: Findings from the 1958
      British birth cohort.
AB  - BACKGROUND: The relationship between adverse childhood experiences (ACE) and
      poorer health across the life course is well established. Increased chronic
      inflammation might be one mechanism through which these associations operate. The
      aim of this study was to explore the relationship between ACE and adult
      inflammation using a prospective longitudinal study. We also investigated whether
      associations were explained by life course socioeconomic, psychological and
      health behavioural factors, and whether associations differed by gender. METHODS:
      Multiply imputed data on 7464 participants of the National Child Development
      Study (1958 British birth cohort) were used. Prospectively collected data on ACE
      included care placement, physical neglect, parental separation, family history of
      offences, mental illness, domestic conflict and alcohol misuse across childhood
      (0-16 years). Adult inflammation was indicated by C-reactive protein (CRP),
      fibrinogen and Von Willebrand factor (vWF) at age 44/45. Multivariable linear
      regression models were used to estimate associations between ACE and adult
      inflammation. RESULTS: Graded associations for ACE with CRP and fibrinogen were
      observed (e.g. CRP: 1 ACE: 4.61% higher, 95% CI: -3.13, 12.97; 2+ ACE: 16.35%
      higher, 95% CI: 6.87, 26.66). Socioeconomic and health behavioral factors were
      found to particularly explain these associations. After inclusion of all
      covariates associations between ACE and mid-life inflammation were no longer
      significant. Associations did not differ for men and women. CONCLUSIONS: ACE were
      associated in a graded manner with adult inflammation in a British birth cohort.
      The association was explained by life course socioeconomic and health behavioral
      factors, in particular. This study highlights the importance of protecting
      children from ACE and its negative health effects, and in supporting children
      through education and into skilled, secure work.

PMID- 29458197
TI  - Changes in motor function, cognition, and emotion-related behavior after right
      hemispheric intracerebral hemorrhage in various brain regions of mouse.
AB  - Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of
      ICH, induced by collagenase or blood infusion, commonly target striatum, but not
      other brain sites such as ventricular system, cortex, and hippocampus. Few
      studies have systemically investigated brain damage and neurobehavioral deficits
      that develop in animal models of ICH in these areas of the right hemisphere.
      Therefore, we evaluated the brain damage and neurobehavioral dysfunction
      associated with right hemispheric ICH in ventricle, cortex, hippocampus, and
      striatum. The ICH model was induced by autologous whole blood or collagenase VII
      S (0.075 units in 0.5 ul saline) injection. At different time points after ICH
      induction, mice were assessed for brain tissue damage and neurobehavioral
      deficits. Sham control mice were used for comparison. We found that ICH location
      influenced features of brain damage, microglia/macrophage activation, and
      behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system
      was most sensitive for evaluating locomotor abnormalities in all four models,
      especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for
      evaluating locomotor abnormalities in models of striatal, intraventricular, and
      cortical ICH. The cylinder test identified locomotor abnormalities only in the
      striatal ICH model. The novel object recognition test was effective for
      evaluating recognition memory dysfunction in all models except for striatal ICH.
      The tail suspension test, forced swim test, and sucrose preference test were
      effective for evaluating emotional abnormality in all four models but did not
      correlate with severity of brain damage. These results will help to inform future
      preclinical studies of ICH outcomes.

PMID- 29458199
TI  - Alpha-synuclein oligomers impair memory through glial cell activation and via
      Toll-like receptor 2.
AB  - Alpha-synuclein oligomers (alpha-synOs) are emerging as crucial factors in the
      pathogenesis of synucleinopathies. Although the connection between
      neuroinflammation and alpha-syn still remains elusive, increasing evidence
      suggests that extracellular moieties activate glial cells leading to neuronal
      damage. Using an acute mouse model, we explored whether alpha-synOs induce memory
      impairment in association to neuroinflammation, addressing Toll-like receptors 2
      and 4 (TLR2 and TLR4) involvement. We found that alpha-synOs abolished mouse
      memory establishment in association to hippocampal glial activation. On brain
      slices alpha-synOs inhibited long-term potentiation. Indomethacin and Ibuprofen
      prevented the alpha-synOs-mediated detrimental actions. Furthermore, while the
      TLR2 functional inhibitor antibody prevented the memory deficit, oligomers
      induced memory deficits in the TLR4 knockout mice. In conclusion, solely alpha
      synOs induce memory impairment likely inhibiting synaptic plasticity. alpha-synOs
      lead to hippocampal gliosis that is involved in memory impairment. Moreover,
      while the oligomer-mediated detrimental actions are TLR2 dependent, the
      involvement of TLR4 was ruled out.

PMID- 29458200
TI  - Influence of treatment modality on morbidity and mortality in periprosthetic
      femoral fracture. A comparative study of 71 fractures treated by internal
      fixation or femoral implant revision.
AB  - INTRODUCTION: The incidence of periprosthetic femoral fracture is constantly
      increasing, with high associated morbidity and mortality. Surgical treatment is
      guided by the Vancouver classification, but the influence of type of treatment on
      morbidity and mortality has been little analyzed. The theoretical advantage of
      implant revision over internal fixation is that it should allow earlier weight
      bearing, although the impact of this on morbidity and mortality and autonomy has
      not been demonstrated. We conducted a case-control study, to assess the influence
      of type of treatment (implant revision or internal fixation) (1) on mobility and
      autonomy and (2) on morbidity and mortality. HYPOTHESIS: The study hypothesis was
      that clinical results and morbidity and mortality do not differ between these two
      types of treatment. METHODS: A retrospective study included 70 patients with a
      total of 71 femoral periprosthetic fractures treated between 2007 and 2014. Two
      treatment groups, comparable for mean age, gender and ASA and Parker scores, were
      studied. Mean age was 78+/-13.5years (range, 23-95years). Thirty-six fractures
      (50.7%) were treated by implant revision via a posterolateral approach, using a
      revision stem with (n=11) or without cement (n=25) (REVISION group); immediate
      postoperative weight-bearing was authorized. Thirty-five fractures (49.3%) were
      treated by open reduction and internal fixation, using a locking plate (ORIF
      group); weight-bearing was authorized only in the third month. Mean follow-up was
      43+/-27months (range, 0.75-107months). RESULTS: Autonomy on Parker score was
      reduced by 2 points at 1year's follow-up. Mean preoperative scores were 7.32+/
      1.79 (range, 3-9) and 7.43+/-1.79 (range, 4-9) in the REVISION and ORIF group,
      respectively, (p=0.8), falling to 5.06+/-2.6 (range, 0-9) and 4.5+/-2.01 (range,
      0-9) respectively at follow-up (p=0.349). Sixteen patients in the REVISION group
      versus 13 in the ORIF group had made adaptations in their home or changed place
      of residence (p=0.2). At last follow-up, 18 patients (28.6%) had died: 12 (37.5%)
      in the ORIF and 6 (19.3%) in the REVISION group (p<0.05). Survival with death as
      endpoint at a mean 3.5years was 88+/-11% in the REVISION group versus 51+/-11% in
      the ORIF group (p=0.02). Three implant replacements were performed in each group
      (p=0.83). Twelve medical or surgical complications occurred in the ORIF group
      (37.5%) and 11 in the REVISION group (34%) (p=0.9). CONCLUSION: Implant revision
      for periprosthetic femoral fracture showed significantly lower overall mortality
      than internal fixation, without difference in terms of treatment failure or
      complications requiring revision surgery. LEVEL OF EVIDENCE: Level III, case
      control study.

PMID- 29458201
TI  - Computer-assisted surgery in acetabular fractures: Virtual reduction of
      acetabular fracture using the first patient-specific biomechanical model
      simulator.
AB  - : Preoperative planning for the management of acetabular fracture is founded on
      geometric models allowing virtual repositioning of the bone fragments, but not
      taking account of soft tissue and the realities of the surgical procedure. The
      present technical note reports results using the first simulator to be based on a
      patient-specific biomechanical model, simulating the action of forces on the
      fragments and also the interactions between soft issue and bone: muscles,
      capsules, ligaments, and bone contacts. In all 14 cases, biomechanical simulation
      faithfully reproduced the intraoperative behavior of the various bone fragments
      and reduction quality. On Matta's criteria, anatomic reduction was achieved in 12
      of the 14 patients (86%; 0.25mm+/-0.45 [range: 0-1]) and in the 12 corresponding
      simulations (86%; 0.42mm+/-0.51 [range: 0-1]). Mean semi-automatic segmentation
      time was 156min+/-37.9 [range: 120-180]. Mean simulation time was 23min+/-9
      [range: 16-38]. The model needs larger-scale prospective validation, but offers a
      new tool suitable for teaching purposes and for assessment of surgical results in
      acetabular fracture. LEVEL OF EVIDENCE: IV: retrospective study.

PMID- 29458202
TI  - Validity of the intra-operative measurement of stem anteversion and factors for
      the erroneous estimation in cementless total hip arthroplasty using postero
      lateral approach.
AB  - BACKGROUND: Intra-operative estimation of stem anteversion in total hip
      arthroplasty (THA) using postero-lateral approach is made by the surgeon's visual
      assessment, using the tibia as a guide, with the assumption that tibial axis is
      vertical to the trans-epicondylar axis. However, the accuracy of the intra
      operative estimation has rarely been verified with postoperative CT-scans, with
      controversies regarding these measurements particularly in case of knee
      osteoarthritis. Therefore we performed a prospective study to: (1) determine the
      accuracy of the intra-operative measurement and (2) investigate factors affecting
      the discrepancy between the surgeon's estimation and the real stem anteversion.
      HYPOTHESIS: Intra-operative estimation of stem anteversion correlated with the
      real stem anteversion on CT-scan. PATIENTS AND METHODS: Sixty-seven THAs using
      cementless straight stems (65 patients) without ipsilateral total knee
      arthroplasty were prospectively evaluated to compare the intra-operative
      measurement of stem anteversion with the real stem anteversion on computed
      tomography (CT) scans. There were 33 men and 34 women with a mean age of
      59.7years (range, 27-84years) at the time of surgery. Age, tibia plateau angle,
      native femoral anteversion, femoro-tibial angle, body mass index, operative site,
      gender, coronal and sagittal tilt of the stem, stem type, ipsilateral knee
      osteoarthritis, and preoperative diagnosis were analyzed to evaluate the factors
      affecting the discrepancy between the intra-operative and CT measurements.
      RESULTS: The intra-operative estimation (mean, 21.5 degrees +/-8.5 degrees ;
      range, 5.0 degrees -39.0 degrees ) was greater than the CT measurement (mean,
      19.5 degrees +/-8.7 degrees ; range, 4.5 degrees -38.5 degrees ) by 2.0 degrees .
      The mean absolute value of discrepancy was 4.5 degrees . The correlation
      coefficient between intra-operative and CT measurements was 0.837. The femoro
      tibial angle was associated with the discrepancy between the two measurements. In
      the presence of genu varum deformity, the intra-operative measurement
      underestimated the stem anteversion. DISCUSSION: Although intra-operative
      estimation of stem anteversion was slightly greater than the real stem
      anteversion, there was an excellent correlation between the two. The femoro
      tibial angle should be considered to optimize the stem anteversion during
      cementless THA using postero-lateral approach. LEVEL OF EVIDENCE: Level III,
      prospective case control study.

PMID- 29458203
TI  - Precision pharmacology for Alzheimer's disease.
AB  - The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents
      significant challenges for drug development. AD pathophysiology is progressing in
      a non-linear dynamic fashion across multiple systems levels - from molecules to
      organ systems - and through adaptation, to compensation, and decompensation to
      systems failure. Adaptation and compensation maintain homeostasis: a dynamic
      equilibrium resulting from the dynamic non-linear interaction between genome,
      epigenome, and environment. An individual vulnerability to stressors exists on
      the basis of individual triggers, drivers, and thresholds accounting for the
      initiation and failure of adaptive and compensatory responses. Consequently, the
      distinct pattern of AD pathophysiology in space and time must be investigated on
      the basis of the individual biological makeup. This requires the implementation
      of systems biology and neurophysiology to facilitate Precision Medicine (PM) and
      Precision Pharmacology (PP). The regulation of several processes at multiple
      levels of complexity from gene expression to cellular cycle to tissue repair and
      system-wide network activation has different time delays (temporal scale)
      according to the affected systems (spatial scale). The initial failure might
      originate and occur at every level potentially affecting the whole dynamic
      interrelated systems within an organism. Unraveling the spatial and temporal
      dynamics of non-linear pathophysiological mechanisms across the continuum of
      hierarchical self-organized systems levels and from systems homeostasis to
      systems failure is key to understand AD. Measuring and, possibly, controlling
      space- and time-scaled adaptive and compensatory responses occurring during AD
      will represent a crucial step to achieve the capacity to substantially modify the
      disease course and progression at the best suitable timepoints, thus
      counteracting disrupting critical pathophysiological inputs. This approach will
      provide the conceptual basis for effective disease-modifying pathway-based
      targeted therapies. PP is based on an exploratory and integrative strategy to
      complex diseases such as brain proteinopathies including AD, aimed at identifying
      simultaneous aberrant molecular pathways and predicting their temporal impact on
      the systems levels. The depiction of pathway-based molecular signatures of
      complex diseases contributes to the accurate and mechanistic stratification of
      distinct subcohorts of individuals at the earliest compensatory stage when
      treatment intervention may reverse, stop, or delay the disease. In addition,
      individualized drug selection may optimize treatment safety by decreasing risk
      and amplitude of side effects and adverse reactions. From a methodological point
      of view, comprehensive "omics"-based biomarkers will guide the exploration of
      spatio-temporal systems-wide morpho-functional shifts along the continuum of AD
      pathophysiology, from adaptation to irreversible failure. The Alzheimer Precision
      Medicine Initiative (APMI) and the APMI cohort program (APMI-CP) have commenced
      to facilitate a paradigm shift towards effective drug discovery and development
      in AD.

PMID- 29458204
TI  - A review of implantable biosensors for closed-loop glucose control and other drug
      delivery applications.
AB  - Closed-loop drug delivery promises autonomous control of pharmacotherapy through
      the continuous monitoring of biomarker levels. For decades, researchers have
      strived for portable closed-loop systems capable of treating ambulatory patients
      with chronic conditions such as diabetes mellitus. After years of development,
      the first of these systems have left the laboratory and entered commercial use.
      This long-awaited advance reflects recent development of chronically stable
      implantable biosensors able to accurately measure biomarker levels in vivo. This
      review discusses the role of implantable biosensors in closed-loop drug delivery
      applications, with the intent to provide a resource for engineers and researchers
      studying such systems. We provide an overview of common biosensor designs and
      review the principle challenges in implementing long indwelling sensors: namely
      device sensitivity, selectivity, and lifetime. This review examines novel
      advances in transducer design, biological interface, and material
      biocompatibility, with a focus on recent academic and commercial work which
      provide successful strategies to overcome perennial challenges. This review
      focuses primarily on the topics of closed-loop glucose control and continuous
      glucose monitoring biosensors, which make up the overwhelming majority of
      published research in this area. We conclude with an overview of recent advances
      in closed-loop systems targeting applications outside blood glucose management.

PMID- 29458205
TI  - Developing a stable aqueous enteric coating formulation with hydroxypropyl
      methylcellulose acetate succinate (HPMCAS-MF) and colloidal silicon dioxide as
      anti-tacking agent.
AB  - The purpose of this study was to use statistical design of experiments to develop
      a stable aqueous enteric coating formulation containing stabilizing excipients,
      such as polyethylene glycol that can minimize hydroxypropyl methylcellulose
      acetate succinate aggregation and minimize spray-nozzle clogging at elevated
      processing temperatures. The mechanisms of stabilization (i.e. charge
      stabilization and molecular interactions) were studied by performing zeta
      potential and FTIR studies. Electrostatic stabilization by sodium lauryl sulfate
      and hydrogen bonding by polyethylene glycol provided dispersion stability and
      yielded a stable aqueous coating formulation that prevented spray-nozzle
      clogging. An enteric coated tablet with better gastric resistance was obtained by
      incorporating fumed silica (Aerosil(r) R972) as the anti-tacking agent instead of
      talc. Dissolution testing on the riboflavin enteric coated tablets showed a good
      enteric release profile without releasing riboflavin in 0.1 N HCl, and completely
      disintegrating within 10 min in phosphate buffer (pH 6.8).

PMID- 29458206
TI  - Mucoadhesive self-emulsifying delivery systems for ocular administration of
      econazole.
AB  - AIM: Development of mucoadhesive self-emulsifying drug delivery systems (SEDDS)
      providing a prolonged ocular residence time for poorly soluble active
      pharmaceutical ingredient. METHODS: l-Cysteine was covalently linked to 6
      mercaptonicotinamide. The obtained ligand, Cysteine-6-mercaptonicotinamide (Cys-6
      MNA) was attached to Eudragit(r) L100-55 via a carbodiimide mediated amide bond
      formation. The resulting entirely S-protected thiolated Eudragit(r) L100-55 was
      characterized regarding the degree of modification as well as stability toward
      oxidation in the presence of strong oxidizing agent (H2O2). The S-protected
      thiolated Eudragit(r) L100-55 was incorporated into SEDDS via hydrophobic ion
      pairing with benzalkonium chloride (BAK) in a concentration of 2% (m/m). S
      protected thiolated Eudragit(r) L100-55-BAK ion pair SEDDS (S-protected thiolated
      EU-BAK SEDDS) were characterized regarding their physicochemical and mucoadhesive
      properties. Econazole nitrate (EN) was incorporated into SEDDS in concentration
      of 1% (m/m) and in vitro drug release was assessed. Furthermore, toxicity study
      was performed on procine corneas via resazurin assay. RESULTS: The entirely S
      protected thiolated Eudragit(r) L100-55 exhibited 282 +/- 78.25 umol of MNA per
      gram of polymer. Ellman's test confirmed no free thiol groups and stability study
      showed no significant increase in dynamic viscosity overtime. The droplet size of
      developed SEDDS in simulated lacrimal fluid was below 100 nm with polydispersity
      index below 0.3. S-protected thiolated EU-BAK SEDDS exhibited 2.5-fold higher
      mucoadhesive properties than blank SEDDS on ocular mucosa. S-protected thiolated
      EU-BAK SEDDS showed sustained EN release over period of 8 h and no pronounced
      corneal toxicity in 0.5% (m/v) concentration. CONCLUSION: Accordingly, these
      mucoadhesive SEDDS can be considered as promising ocular delivery system for EN.

PMID- 29458207
TI  - Co-spray drying of hygroscopic kanamycin with the hydrophobic drug rifampicin to
      improve the aerosolization of kanamycin powder for treating respiratory
      infections.
AB  - High dose delivery of drugs to the lung using a dry powder inhaler (DPI) is an
      emerging approach to combat drug-resistant local infections. To achieve this,
      highly aerosolizable powders are required. We hypothesized that co-spray-drying
      kanamycin, a hydrophilic hygroscopic antibiotic, with rifampicin, a hydrophobic
      antibiotic, would produce inhalable particles with surfaces enriched in
      rifampicin. Such particles would have higher aerosolization than kanamycin alone,
      and minimise the mass of powder for inhalation avoiding use of non-active
      excipients. Kanamycin was co-spray-dried with rifampicin using a Buchi Mini Spray
      dryer. All powders were inhalable in size (1.1-5.9 um) and noncrystalline. X-ray
      photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass
      spectrometry (ToF-SIMS) showed the surface of the combination powder was enriched
      with rifampicin. In vitro aerosolization (fine particle fraction) determined by
      next generation impactor (NGI), dramatically improved from 29.5 +/- 0.2%
      (kanamycin-only) to 78.2 +/- 1.3% (kanamycin-rifampicin combination). The
      combination powder was flake-shaped in morphology, stable at 15% and 53% RH and
      25 +/- 2  degrees C during one-month storage in an open Petri dish, and non-toxic
      (up to 50 ug/mL) to human alveolar and bronchial cell-lines. Surface enrichment
      of kanamycin by hydrophobic rifampicin improves aerosolization, which may help to
      combat drug-resistant local infections by facilitating high dose delivery to deep
      lung.

PMID- 29458208
TI  - The use of fatty acids as absorption enhancer for pulmonary drug delivery.
AB  - A limitation in the systemic uptake of many inhalable drugs is the restricted
      permeation through the pulmonary epithelial layer barrier. One strategy to bypass
      the epithelial layer when delivering non-permeable drugs is to alter the
      paracellular transport, allowing the uptake of drugs into the systemic
      circulation. In this study, the potential of sodium decanoate (Na dec),
      docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as absorption
      enhancers has been investigated to increase pulmonary paracellular permeability
      by modulating epithelial cells' tight junctions. By incorporating Na dec, DHA and
      EPA, separately, into a nebulising formulation, the aim was to enhance the
      absorption of a fluorescent marker (flu-Na, used as model drug) across pulmonary
      epithelial cells (Calu-3). Results indicate that the aerosol performance of all
      the nebulizing formulations containing absorption enhancers was significantly
      better than control. Furthermore, the in vitro cell assays demonstrated a
      significant increase in paracellular transport of the fluorescent marker with Na
      dec and DHA formulations. This finding supports the potential use ofDHA and Na
      dec to enhance epithelial transport of poorly permeable drugs delivered via
      inhalation.

PMID- 29458209
TI  - Dermal anti-oxidant, anti-inflammatory and anti-aging effects of Compritol ATO
      based Resveratrol colloidal carriers prepared using mixed surfactants.
AB  - In this study, Compritol ATO-based Resveratrol colloidal carriers (CCCs) were
      prepared and subjected to characterization and evaluation. In most formulae, the
      use of a binary-mixture of surfactants improved the physicochemical properties.
      CCC6 (containing P407/P188 as bi-surfactants) attained the highest drug loading,
      release efficiency during 24 h and occlusive effect for 48 h; in addition, it
      showed a uniform particle size distribution within the desired range. In-vivo
      studies were done based on the analysis of anti-oxidant markers [catalase (CAT),
      reduced glutathione (GSH) and superoxide dismutase (SOD)], anti-inflammatory
      markers [interleukin 6 (IL-6), interleukin 8 (IL-8) and rat Nuclear factor-kappa
      B (NF-kappaB)] and anti-wrinkling markers [matrix metalloproteinase (MMP-1) and
      Granulocyte-macrophage colony-stimulating factor (GM-CSF)], after UVB
      irradiation. Results were significantly different when comparing the positive
      control and the negative control groups (p < 0.05). Rats pre-treated with CCC6
      showed a great amelioration, and the level of the biochemical markers was
      significantly different compared to those of the positive control group and those
      pre-treated with the drug suspension (p < 0.05). Also, the high skin protective
      effect of CCC6 was proved by visual and histopathological examination of the
      rats' skin. Therefore, the current study proves the beneficial effects of the
      designed dermal Resveratrol-loaded colloidal system.

PMID- 29458210
TI  - Preparation of a solid self-microemulsifying drug delivery system by hot-melt
      extrusion.
AB  - Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical
      industry; however, its potential in the preparation of solid self-emulsifying
      drug delivery systems (S-SMEDDS) is still unexplored. This study sought to
      prepare enteric S-SMEDDS by HME and evaluate the effects of the process and
      formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid
      SMEDDS were developed, and carvedilol was used as a class II model drug. Mean
      size, polydispersity index (PdI) and zeta potential of the resulting
      microemulsions were determined. The extrudates were then obtained by blending the
      lipid mixture and HPMCAS using a twin-screw hot-melt extruder. SEM, optical
      microscopy and PXRD were used to characterize the extrudates. In vitro
      microemulsion reconstitution and drug release were also studied. L-SMEDDS gave
      rise to microemulsions with low mean size, PdI and zeta potential (140.04 +/-
      7.22 nm, 0.219 +/- 0.011 and -9.77 +/- 0.86 mV). S-SMEDDS were successfully
      prepared by HME, and an HMPCAS matrix was able to avoid microemulsion
      reconstitution and retain drug release in pH 1.2 (12.97%-25.54%). Conversely,
      microemulsion reconstitution and drug release were gradual in pH 6.8 and complete
      for some formulations. Extrudates prepared at the lowest drug concentration and
      highest temperature and recirculation time promoted a complete and rapid drug
      release in pH 6.8 giving rise to small and uniform microemulsion droplets.

PMID- 29458211
TI  - Impact of formulation excipients on the thermal, mechanical, and electrokinetic
      properties of hydroxypropyl methylcellulose acetate succinate (HPMCAS).
AB  - Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has been widely used in
      amorphous solid dispersions and as an enteric coating polymer. Under aqueous
      coating conditions and at elevated coating temperatures, HPMCAS particles tend to
      aggregate and clog the spray-nozzle, hence interrupting the coating process. This
      research focused on how plasticizers and surfactants, excipients used for aqueous
      coating, affect the properties and stability of HPMCAS. This information would be
      useful in identifying suitable excipients for developing a stable HPMCAS aqueous
      enteric coating formulation. Triethyl citrate was found to be the most compatible
      plasticizer with HPMCAS, and displayed suitable thermal and mechanical
      properties. PEG 4000, the co-plasticizer, provided dispersion stability by
      yielding a dispersible sediment without aggregation at the elevated processing
      temperatures. Zeta potential measurements indicated sodium lauryl sulfate (SLS)
      could be used as a potential stabilizing agent at concentrations above its
      critical micelle concentration (CMC). This study facilitated the understanding of
      the HPMCAS aggregation mechanism, in addition to identifying suitable stabilizing
      agents. These stabilizing excipients could potentially be used to develop a
      stable aqueous coating formulation that does not exhibit polymer aggregation and
      nozzle clogging during the coating process.

PMID- 29458212
TI  - Programmed drug delivery system based on optimized "size decrease and
      hydrophilicity/hydrophobicity transformation" for enhanced hepatocellular
      carcinoma therapy of doxorubicin.
AB  - Requirements on drug delivery systems to surmount a complex series of
      pathophysiological barriers bear "cascading contradictions", especially size and
      hydrophilicity/hydrophobicity contradiction. Herein, a programmed drug delivery
      system (GNPs-Dox-Lac) based on optimized "size decrease and
      hydrophilicity/hydrophobicity transformation" was developed by combination the
      gelatin nanoparticle (GNPs) and prodrug Doxorubicin-Lactose (Dox-Lac). The
      results showed that GNPs-Dox-Lac (133.3 nm) were kinetically stable in blood
      circulation and inclined to accumulate at the tumor site. Then the degradation of
      the GNPs triggered by tumor extracellular matrix metalloproteinase-2 (MMP2) led
      to the release of prodrug Dox-Lac (Mw 898 Da) to facilitate the tumor tissue
      penetration and cellular uptake. Last, pH-responsive disassociation of Dox-Lac in
      tumor cells resulted in the free Dox (Mw 543 Da) release to induce toxicity. As
      expected, GNPs-Dox-Lac achieved superior tumor inhibition rate of 90.8% with low
      toxicity in vivo, suggesting its potential for enhanced hepatocellular carcinoma
      (HCC) therapy of doxorubicin in future.

PMID- 29458213
TI  - Selective targeting and degradation of doxorubicin-loaded folate-functionalized
      DNA nanocages.
AB  - Selective targeting is a crucial property of nanocarriers used for drug delivery
      in cancer therapy. We generated biotinylated octahedral DNA nanocages
      functionalized with folic acid through bio-orthogonal conjugation chemistry.
      Molecular modelling indicated that a distance of about 2.5 nm between folic acid
      and DNA nanocage avoids steric hindrance with the folate receptor. HeLa cells, a
      folate receptor positive tumour cell line, internalize folate-DNA nanocages with
      efficiency greater than 40 times compared to cells not expressing the folate
      receptors. Functionalized DNA nanocages are highly stable, not cytotoxic and can
      be efficiently loaded with the chemotherapeutic agent doxorubicin. After entry
      into cells, doxorubicin-loaded nanoparticles are confined in vesicular
      structures, indicating that DNA nanocages traffic through the endocytic pathway.
      Doxorubicin release from loaded DNA cages, facilitated by low pH of endocytic
      vesicles, induces toxic pathways that, besides selectively killing folate
      receptor-positive cancer cells, leads to cage degradation avoiding nanoparticles
      accumulation inside cells.

PMID- 29458214
TI  - Effect of tetrahedral DNA nanostructures on proliferation and osteo/odontogenic
      differentiation of dental pulp stem cells via activation of the notch signaling
      pathway.
AB  - Dental pulp stem cells (DPSCs) derived from the human dental pulp tissue have
      multiple differentiation capabilities, such as osteo/odontogenic differentiation.
      Therefore, DPSCs are deemed as ideal stem cell sources for tissue regeneration.
      As new nanomaterials based on DNA, tetrahedral DNA nanostructures (TDNs) have
      tremendous potential for biomedical applications. Here, the authors aimed to
      explore the part played by TDNs in proliferation and osteo/odontogenic
      differentiation of DPSCs, and attempted to investigate if these cellular
      responses could be driven by activating the canonical Notch signaling pathway.
      Upon exposure to TDNs, proliferation and osteo/odontogenic differentiation of
      DPSCs were dramatically enhanced, accompanied by up regulation of Notch
      signaling. In general, our study suggested that TDNs can significantly promote
      proliferation and osteo/odontogenic differentiation of DPSCs, and this remarkable
      discovery can be applied in tissue engineering and regenerative medicine to
      develop a significant and novel method for bone and dental tissue regeneration.

PMID- 29458215
TI  - Factors Associated with Placental Vascularization Measured by 3D Power Doppler
      Ultrasonographic Sphere Biopsy between 11 and 14 Weeks of Gestation.
AB  - OBJECTIVE:  Preeclampsia is associated with placental vascularization disorders.
      Ultrasonographic sphere biopsy (USSB) of the placenta can estimate the
      vascularization of the placenta and potentially the risk of preeclampsia. We
      aimed to explore the factors related to placental vascularization measured with
      USSB in the first trimester. STUDY DESIGN:  A prospective cohort was conducted in
      women recruited at 11 to 14 weeks. Three-dimensional acquisition of the placenta
      with power Doppler was undertaken along with crown-rump length (CRL). Using USSB
      of the full placental thickness at its center, vascularization index, flow index,
      and vascular flow index were measured. Pearson's correlation coefficients and
      multivariate linear regression were used to correlate the vascularization indices
      with CRL and maternal characteristics. RESULTS:  A total of 5,612 women were
      recruited at a mean gestational age of 12.8 +/- 0.6 weeks. We observed that
      vascularization indices increase with CRL. After adjustment, we observed that
      maternal age, ethnicity other than Caucasian, and body mass index were associated
      with lower vascularization indices, while diabetes, smoking, and assisted
      reproduction technology were not. We observed that parous women without history
      of preeclampsia had greater vascularization indices compared with nulliparous
      women. CONCLUSION:  Placental vascularization indices assessed by USSB fluctuate
      with gestational age, ethnicity, maternal age, body mass index, and previous
      pregnancy history.

PMID- 29458216
TI  - Institution of a Comprehensive Postpartum Hemorrhage Bundle at a Large Academic
      Center does not Immediately Reduce Maternal Morbidity.
AB  - OBJECTIVE:  Obstetric hemorrhage is a leading cause of morbidity and mortality.
      We sought to assess whether institution of a postpartum hemorrhage (PPH) bundle
      could improve maternal morbidity in our population. STUDY DESIGN: 
      Preintervention data (PRE) was collected on all deliveries at Hospital of the
      University of Pennsylvania between October 15, 2013 and December 15, 2013. A two
      pronged, multidisciplinary educational and procedural intervention related to PPH
      was instituted from March 2015 to June 2015. Postintervention data (POST) was
      collected on all deliveries from October 20, 2015 to December 20, 2015. RESULTS: 
      Note that 592 of 626 (95%) PRE and 583 of 613 (95%) POST deliveries were
      included. The rates of PPH by estimated blood loss (EBL) >= 1,000 mL and by 3 g
      hemoglobin drop were not significantly different from PRE to POST (9.0% versus
      12.2%, p = 0.07 and 10.5% versus 13.5%, p = 0.10, respectively). There was no
      significant change in transfusion rate (3.4% versus 5.1%, p = 0.13). Use of
      uterotonics was reduced from 9.8 to 6.3% from PRE to POST (p = 0.03). CONCLUSION:
      While institution of a PPH bundle is designed to improve the morbidity of PPH,
      our data demonstrate that it cannot be expected to do so within 6 months of
      implementation. Further studies will need to assess the long-term effects of such
      a resource-intensive protocol, including perceptions of improved safety by all
      providers, nurses, and staff.

PMID- 29458217
TI  - A New Two-Dimensional Shear Wave Elastography for Noninvasive Assessment of Liver
      Fibrosis in Healthy Subjects and in Patients with Chronic Liver Disease.
AB  - PURPOSE:  To assess the performance of two-dimensional shear wave elastography
      (2D-SWE) on the GE LOGIQ E9 ultrasound system in a cohort of healthy subjects and
      to investigate its accuracy in the staging of liver fibrosis in patients with
      chronic liver disease (CLD) using liver biopsy as a reference standard. MATERIALS
      AND METHODS:  From October 2014 to June 2016, 54 healthy subjects and 174
      patients with CLD were consecutively enrolled. Liver fibrosis stage was assessed
      by the METAVIR scoring system. 18 (10.3 %) and 17 (9.8 %) patients had advanced
      fibrosis and cirrhosis, respectively. The correlation of liver stiffness
      measurement (LSM) and continuous variable was assessed using the Spearman rank
      correlation. The accuracy of 2D-SWE was evaluated with areas under the receiver
      operating characteristics curves (AUROC). RESULTS:  Reliable LSMs were obtained
      in all subjects. The interobserver agreement ICC was excellent: 0.847. In healthy
      subjects, gender, but not anthropometric and biochemical data, were correlated
      with LSM. In patients with CLD, LSM had a strong positive correlation with
      fibrosis stage (rho = 0.628; p > 0.001). The AUROC was 0.724 for mild fibrosis
      (F>= 1), 0.857 for moderate fibrosis (F>= 2), 0.946 for severe fibrosis (F>= 3),
      and 0.935 for cirrhosis (F4). Likewise, good accuracy was observed in the HCV
      subgroup. The optimal cut-off value in differentiating healthy subjects from CLD
      patients with any fibrosis was 5.47 kPa with an AUROC of 0.875. CONCLUSION:  2D
      SWE is a reliable and reproducible method to assess LSM with good diagnostic
      accuracy to assess liver fibrosis in patients with CLD.

PMID- 29458218
TI  - Effects of Curcuminoids Plus Piperine on Glycemic, Hepatic and Inflammatory
      Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind
      Placebo-Controlled Trial.
AB  - INTRODUCTION: Curcuminoids have been shown to reduce glycemia and related
      complications in diabetes. In the present study, we evaluated the impact of
      curcuminoids plus piperine administration on glycemic, hepatic and inflammatory
      biomarkers in type 2 diabetes (T2D) patients. METHODS: T2D patients aged 18-65
      years were enrolled in a randomized double-blind placebo-controlled trial and
      randomly allocated to standard-of-care treatment and dietary advises plus either
      curcuminoids (daily dose of 500 mg/day co-administered with piperine 5 mg/day) or
      placebo for a period of 3 months. Glycemic, hepatic and inflammatory parameters
      were measured at baseline and final conditions. RESULTS: A total of 100 subjects
      (50 in each group) completed the 3-month period of trial. A significant reduction
      was found in serum levels of glucose (-9+/-16 mg/dL vs. -3+/-11 mg/dL in
      curcuminoids and placebo groups, respectively; p=0.048), C-peptide (-0.6+/-0.8
      ng/mL vs. 0.02+/-0.6 ng/mL; p<0.001) and HbA1c (-0.9+/-1.1% vs. -0.2+/-0.5%;
      p<0.001) after curcuminoids supplementation versus placebo group. Additionally,
      participants in the intervention group showed lower serum alanine
      aminotransferase (-2+/-6 vs. -1+/-5; p=0.032) and aspartate aminotransferase (
      3+/-5 vs. -0.3+/-4; p=0.002) levels compared with the placebo group. Finally, no
      significant differences in high-sensitivity C-reactive protein (hs-CRP)
      concentrations were observed between curcuminoids and placebo groups (p>0.05).
      CONCLUSION: The results of the present trial revealed a beneficial effect of
      curcuminoids plus piperine supplementation on glycemic and hepatic parameters but
      not on hs-CRP levels in T2D patients.

PMID- 29458219
TI  - Clinical, Endocrine and Imaging Characteristics of Patients with Primary
      Hypophysitis.
AB  - Primary hypophysitis (PH) is a rare disease with a poorly-defined natural
      history. Our aim was to characterise patients with PH at presentation and during
      prolonged follow-up. Observational retrospective study of 22 patients was
      conducted from 3 centres. In 14 patients, PH was confirmed histologically and in
      the remaining 8 clinically, after excluding secondary causes of hypophysitis. All
      patients had hormonal and imaging investigations before any treatment. Median
      follow up was 48 months (25-75%: 3-60). There was a female predominance with a
      female/male ratio: 3.4:1. Eight out of 22 patients had another autoimmune
      disease. Headaches and gonadal dysfunction were the most common symptoms. Five
      patients presented with panhypopituitarism; 17 patients had anterior pituitary
      deficiency, and 7 had diabetes insipidus. At presentation, 9 patients were
      treated surgically, 5 received replacement hormonal treatment, and 8 high-dose
      glucocorticoids from whom 5 in association with other immunosuppressive agents.
      Six patients showed complete recovery of pituitary hormonal deficiencies while 6
      showed a partial recovery during a 5-year follow-up period. No difference was
      found between patients treated with surgery and those treated medically. The
      overall relapse rate was 18%. PH can be manifested with a broad spectrum of
      clinical and hormonal disturbances. Long-term follow-up is required to define the
      natural history of the disease and response to treatment, since pituitary
      hormonal recovery or relapse may appear many years after initial diagnosis. We
      suggest that surgery and immunosuppressive therapy be reserved for exceptional
      cases.

PMID- 29458220
TI  - Incidence of Autoimmune and Related Disorders After Resolution of Endogenous
      Cushing Syndrome in Children.
AB  - Glucocorticoids are widely used for immunosuppression in autoimmune diseases.
      After the resolution of hypercortisolemia, the immune system recovers allowing
      for autoimmune diseases to manifest. Here we investigated the presence of
      autoimmune and related diseases that developed after cure of endogenous Cushing
      syndrome (CS) in children. We identified 129 children who were diagnosed and
      successfully treated for endogenous CS at the National Institutes of Health from
      1997 until 2017, and who were followed for at least 6 months after treatment. We
      performed a retrospective chart review analysis to identify the presence of
      autoimmune or related diseases after cure. Ten children were diagnosed with a new
      autoimmune or related disorder after resolution of hypercortisolemia. This
      results in a frequency of 7.8% of our pediatric CS population. The identified
      patients had a shorter duration of hypercortisolemia prior to diagnosis, but did
      not otherwise differ from the remaining patients. The various identified diseases
      were: celiac disease (n=1), psoriasis (n=1), Hashimoto thyroiditis (n=1), Graves
      disease (n=1), optic neuritis (n=2), skin hypopigmented lesions/vitiligo (n=2),
      allergic rhinitis/asthma (n=1), and neuropathy responding to glucocorticoid
      treatment (n=1). The reported time between the treatment of CS and diagnosis of
      autoimmune disorder ranged from 6 to 19 months. The presence of autoimmune or
      related diseases might be masked by the hypercortisolemic state in endogenous CS.
      After resolution of hypercortisolemia, the presentation of new autoimmune
      diseases or recurrence of previously known autoimmune conditions should be
      considered when concerning symptoms arise.

PMID- 29458221
TI  - Thyroid-Stimulating Hormone-Stimulated Human Adipocytes Express Thymic Stromal
      Lymphopoietin.
AB  - When recombinant human (rh) thyroid-stimulating hormone (TSH) is administered to
      thyroid cancer survivors, an acute extra-thyroidal effect raises pro-inflammatory
      cytokines and activates platelets. Thymic stromal lymphopoietin (TSLP) is a
      cytokine recently implicated in platelet activation. Our aim was to measure
      platelet microparticle levels after rhTSH stimulation in vivo, and to investigate
      TSLP expression in TSH-stimulated human adipocytes in culture. Blood samples for
      total and platelet microparticle analysis were obtained from thyroid cancer
      survivors before (day 1) and after rhTSH administration (day 5). Adipocytes,
      differentiated from stromal preadipocytes isolated from adipose tissue from
      surgical patients, were stimulated with TSH. TSLP mRNA expression, protein
      expression, and protein release into the adipocyte medium were measured. The
      level of platelet microparticles in thyroid cancer patients rose 5-fold after
      rhTSH stimulation. TSH upregulated TSLP mRNA expression in adipocytes in culture
      through a pathway that was inhibited by 66% by H89, a protein kinase A inhibitor.
      TSLP protein expression rose in response to TSH, and TSH-stimulated TSLP release
      into the medium was completely blocked by dexamethasone. In conclusion, TSLP is a
      novel TSH-responsive adipokine. Future studies will be needed to address the
      potential role of adipocyte-derived TSLP and whether it is linked to TSH
      dependent platelet activation.

PMID- 29458222
TI  - ?

PMID- 29458223
TI  - ?
AB  - INTRODUCTION: The evaluation of plasma levels of antidepressants may improve the
      treatment outcome. The aim was to verify adherence and adequacy of administered
      doses of antidepressants among patients hospitalized for inadequate outpatient
      therapeutic response. METHODS: Selective serotonin reuptake inhibitors or
      venlafaxine plasma levels were assessed on the first day of hospitalization and
      after 3 days of controlled administration. The patients were considered adherent
      if the plasma level on admission was within the interval of the minimum and
      maximum plasma level on the fourth day, expanded by 30%. The adequacy of
      antidepressant doses used during the outpatient treatment was assessed by
      comparing the plasma level on the fourth day with the therapeutic reference
      range. RESULTS: Out of 83 patients, 52 (62.7%) were adherent. The plasma levels
      of antidepressants on the fourth day were found to be within the therapeutic
      reference range in 35 (43.2%) patients. The same number manifested levels below
      the therapeutic reference range. In 11 (13.6%) patients, the levels were higher
      than recommended. No significant difference in rate of adherence was found among
      individual antidepressants. CONCLUSION: The results show that antidepressant
      nonresponders are frequently under-dosed or nonadherent.

PMID- 29458224
TI  - [Lubeck University Model for Physiotherapy].
AB  - The aim of this paper is to describe the development of an innovative bachelor's
      degree program for physiotherapy directly affiliated with the medical department,
      which is a unique approach to making physiotherapy an academic course in Germany.
      The previous system for qualifying as a physiotherapist was amended by the
      adaption of qualification objectives resulting in a model that links scientific
      and vocational knowledge from the beginning of the study. Several lectures
      support interprofessionality. The vocational training is fully integrated into
      the curriculum. The exemplary concept is monitored by an extensive quality
      management program. The approach meets general recommendations of experts and can
      serve as a model for other universities.

PMID- 29458225
TI  - [Indication Quality: Concepts and Ethical Implications].
AB  - BACKGROUND: In recent times - also due to new laws - a good "indication quality"
      has been called for. The aim of this paper is to contribute to the debate about
      "indication quality" by looking into the meaning of the term "indication" as well
      as the meaning of an adequate understanding of quality. METHODS: Initially, a
      conceptual analysis is made of how indication is an integral part of the
      therapeutic decision-making process between physician and patient, in which, next
      to evidence-based elements, also normative elements are included (step 1). In the
      second part, 2 different types of quality are contrasted (step 2): an externally
      quantifiable, standardized quality (Q-quality) and a quality pertaining to the
      individual physician, based on professional ethical values and principles (T
      quality). RESULTS: For good "indication quality" it is suggested that both types
      of quality are included. As for Q-Quality, quantitative measures with selected
      quality indicators are proposed. Regarding T-Quality, qualitative, discursive
      procedures are more appropriate. CONCLUSIONS: It is suggested that the term
      "indication quality" be used for the quality of the whole therapeutic decision
      making process including the indication itself. The indication should be based on
      profession-specific values rather than on other contextual or "private" ethical
      foundations. The legal and societal preconditions should set positive impulses
      for both ways of understanding the term "quality".

PMID- 29458226
TI  - [Outbreaks of Scabies in Schools and Use of Ivermectin].
AB  - BACKGROUND: At Pentecost 2017 outbreaks of scabies occurred in three schools in
      Ploen County. Several classes were supposed to go on an excursion or had returned
      from an excursion with symptomatic kids. METHODS: Rapid investigation, on site
      outbreak confirmation, home visits of the environment of the index cases,
      simultaneous mass treatment and post exposure prophylaxis (PEP) with Ivermectin
      according to the outbreak characteristics were applied. RESULTS: The index case
      of school A was ill since 5 months, but was misdiagnosed as eczema. Not all cases
      were linked to this index case. The entire school was treated in three steps
      within a 10-day period: step 1 began 48 h after notification. The attack rate was
      6.4% (19 out of 298 pupils). A total of 93% of the kids and 100% of the teaching
      staff were treated. For school B with two sporadic and independent cases, an
      alert warning was issued. In school C, the two classes with cases were treated
      and according to the contact pattern two further classes were physically
      examined: 7 out of 39 (18%) of the kids were symptomatic, but none in the contact
      classes. CONCLUSIONS: The endemicity of scabies appears to be much higher than
      previously assumed. With the use of Ivermectin, the local public health
      department could act quickly and demonstrate that interventional public health is
      possible. However, several obstacles had to be overcome, but parents and teachers
      were cooperative and thankful.

PMID- 29458227
TI  - [Award of the Salomon-Neumann-Medal 2017 - Speech of the Laureate Prof. Bernt
      Peter Robra, 5 September 2017, St. Peter's Church Lubeck].
AB  - The Salomon-Neumann-Medal 2017 of the German Society for Social Medicine and
      Prevention (DGSMP) was awarded to Bernt-Peter Robra, Institute for Social
      Medicine and Health Economics (ISMG) of the Otto von Guericke University
      Magdeburg. The person and scientific merits of Manfred Pflanz are valued and
      topics of the masterplan2020-process are highlighted, that offer chances for
      developments in medicine and public health.

PMID- 29458228
TI  - Efficacy of Epidural Analgesia after Laparotomy in Children.
AB  - BACKGROUND:  Epidural analgesia (EDA) is used as postoperative pain treatment in
      children, but little is known about its efficacy after laparotomy in children.
      This retrospective study investigated the efficacy of postoperative EDA after
      laparotomy in children and the frequencies of adverse effects and complications.
      MATERIALS AND METHODS:  Data of all children aged 0 to 18 years undergoing
      laparotomy and treated with EDA in our hospital from January 2014 to December
      2015 were collected. EDA was classified as successful either if the catheter was
      removed when there was no further need, and the patient was comfortable with
      oral/rectal analgesics or when EDA was continued after intervention. RESULTS: 
      Ninety children with a median age of 3.7 years were included in the study. In 65%
      (59/90), EDA was classified as successful. In 34% (20/59) of all successful
      cases, an additional intervention was needed. In 35% (31/90), the catheter was
      removed earlier than planned, in half of these cases after an intervention. The
      primary reason for earlier removal was inadequate analgesia and technical
      failure. Adverse effects occurred in 18% and complications in 1% of cases. The
      successful group was significantly younger than the unsuccessful (p = 0.003).
      CONCLUSION:  EDA after laparotomy positively contributed to postoperative pain
      treatment in two-thirds of children. Numbers of adverse effects and complications
      were low. It is important to optimize pain management after laparotomy in
      children; thus, further prospective studies should focus on optimizing EDA and
      comparing EDA with other techniques of analgesia.

PMID- 29458229
TI  - Primary Closure versus Bedside Silo and Delayed Closure for Gastroschisis: A
      Truncated Prospective Randomized Trial.
AB  - BACKGROUND:  We report a prospective randomized trial comparing primary closure
      (PC) to bedside silo and delayed closure (DC) for babies with gastroschisis.
      METHODS:  Patients were randomized to PC versus DC. We excluded those with
      atresia/necrosis, <34 weeks' gestation, or congenital anomalies. The primary
      outcome was length of stay (LOS). RESULTS:  A total of 38 patients were included
      from August 2011 to August 2016; 18 patients underwent DC and 20 PC. There were
      no differences in gestational age or birth weight. Fifty percent of PC patients
      were successfully closed with the rest closed at a median of 4 days
      (interquartile range [IQR]: 2-4 days). DC patients were closed at a median of 4
      days after silo placement (IQR: 2-5.8 days). None of the patients in this series
      developed abdominal compartment syndrome after closure. Median LOS, median time
      to enteral tolerance, and median time on ventilation were not statistically
      different. Two patients (one DC and one PC) had bowel ischemia and necrosis
      following silo placement requiring reoperation. Four patients (two DC and two PC)
      were noted to have small umbilical defects; none have yet required operative
      correction. CONCLUSION:  There were no differences seen between PC and DC in LOS,
      time to enteral feeds, or ventilator times.

PMID- 29458230
TI  - Perioperative Complications of Congenital Diaphragmatic Hernia Repair.
AB  - Although improvements have been made, the management of congenital diaphragmatic
      hernia (CDH) remains a major challenge for perinatologists and neonatal surgeons.
      Many aspects of the disease remain unknown and, being a rare entity, evidence
      based data are hard to find. Surgical morbidity is considerable and affects long
      term quality of life. Perioperative complications have been reviewed focusing on
      thoracoscopic repair. Intraoperative acidosis was more severe during thoracoscopy
      when compared with open surgery (OS), though it is possible that later
      neurodevelopment was not affected. Even so, strategies have been outlined to
      reduce acidosis, such as decreasing carbon dioxide (CO2) insufflation after
      reduction of the herniated viscera into the abdomen is complete. The risk of
      pleural complications decreased after introduction of gentle ventilation
      techniques and minimally invasive surgery (MIS); thus, the use of a prophylactic
      intraoperative thoracic tube is not routinely required. Recurrence rate was
      higher in large CDH and following MIS repair. Technical demands play an important
      role, therefore, in avoiding complications; every step of the OS technique must
      be strictly accomplished. In large defects, the use of prosthetic patch might
      reduce recurrence rate, even by MIS repair, once again only if technical demands
      are overcome with meticulous rules of suturing. Thoracoscopy significantly
      reduced the incidence of bowel obstruction and recovery time and improved
      cosmesis. The best approach of CDH is yet to be found, and it goes far beyond the
      management of perioperative complications. Meanwhile randomized controlled
      studies, namely on the outcome of thoracoscopic repair, are required to inform
      further practice.

PMID- 29458231
TI  - Perioperative Complications of Transanal Pull-through Surgery for Hirschsprung's
      Disease.
AB  - Transanal pull-through is currently one of the most commonly used operation to
      treat Hirschsprung's disease (HD) worldwide. It has undergone some technical
      modifications during the last decades and still contains variable surgical
      practices. As high quality comparative studies between different surgical
      approaches are missing, debate over the optimal operation for HD still continues.
      Transanal pull-through is associated with multiple potential complications, which
      may result in permanently impaired functional outcome, life-long morbidity, and
      significant social restrictions. Although some of the surgical complications can
      be successfully managed by repeated surgery, the best changes for optimal bowel
      function and fecal continence are lost. Surgical complications are best treated
      by efficient prevention with careful adherence to established surgical techniques
      and principles during the primary operation.

PMID- 29458232
TI  - Fibrinogen and Neopterin Is Associated with Future Myocardial Infarction and
      Total Mortality in Patients with Stable Coronary Artery Disease.
AB  - Systemic fibrinogen and neopterin are related to inflammation. We investigated
      the prognostic utility and possible interactions of these biomarkers in stable
      coronary artery disease (SCAD) patients undergoing coronary angiography. We
      included 3,545 patients with suspected stable angina with a median follow-up of
      7.3 and 10.2 years for incident acute myocardial infarction (AMI) and all-cause
      mortality, respectively. Prospective associations were explored by Cox
      regression. Potential effect modifications were investigated according to strata
      of fibrinogen, neopterin or high-sensitivity troponin T (hsTnT) below and above
      the median, as well as gender and smoking habits. During follow-up, 543 patients
      experienced an AMI and 769 patients died. In a multivariable model, the hazard
      ratios (HRs; 95% confidence interval [CI]) per 1 SD increase for fibrinogen in
      relation to these endpoints were 1.30 (1.20, 1.42; p < 0.001) and 1.22 (1.13,
      1.31; p < 0.001), respectively. For neopterin, the HRs (95% CI) were 1.31 (1.23,
      1.40; p < 0.001) and 1.24 (1.15, 1.34; p < 0.001), respectively. No significant
      interaction between fibrinogen and neopterin was observed. The prognostic utility
      of neopterin for incident AMI was improved in patients with an hsTnT above the
      median, for total mortality in non-smokers, and for both total mortality and AMI
      in females. In conclusion, both fibrinogen and neopterin were associated with
      future AMI and total mortality, but had low discriminatory impact. No interaction
      was observed between these two biomarkers. The prognostic utility of neopterin
      was improved in patients with hsTnT levels above the median, and in females and
      non-smokers.

PMID- 29458233
TI  - Pharmacokinetic Modelling to Predict FVIII:C Response to Desmopressin and Its
      Reproducibility in Nonsevere Haemophilia A Patients.
AB  - BACKGROUND:  Nonsevere haemophilia A (HA) patients can be treated with
      desmopressin. Response of factor VIII activity (FVIII:C) differs between patients
      and is difficult to predict. OBJECTIVES:  Our aims were to describe FVIII:C
      response after desmopressin and its reproducibility by population pharmacokinetic
      (PK) modelling. PATIENTS AND METHODS:  Retrospective data of 128 nonsevere HA
      patients (age 7-75 years) receiving an intravenous or intranasal dose of
      desmopressin were used. PK modelling of FVIII:C was performed by nonlinear mixed
      effect modelling. Reproducibility of FVIII:C response was defined as less than
      25% difference in peak FVIII:C between administrations. RESULTS:  A total of 623
      FVIII:C measurements from 142 desmopressin administrations were available; 14
      patients had received two administrations at different occasions. The FVIII:C
      time profile was best described by a two-compartment model with first-order
      absorption and elimination. Interindividual variability of the estimated baseline
      FVIII:C, central volume of distribution and clearance were 37, 43 and 50%,
      respectively. The most recently measured FVIII:C (FVIII-recent) was significantly
      associated with FVIII:C response to desmopressin (p < 0.001). Desmopressin
      administration resulted in an absolute FVIII:C increase of 0.47 IU/mL (median,
      interquartile range: 0.32-0.65 IU/mL, n = 142). FVIII: C response was
      reproducible in 6 out of 14 patients receiving two desmopressin administrations.
      CONCLUSION:  FVIII:C response to desmopressin in nonsevere HA patients was
      adequately described by a population PK model. Large variability in FVIII:C
      response was observed, which could only partially be explained by FVIII-recent.
      FVIII: C response was not reproducible in a small subset of patients. Therefore,
      monitoring FVIII:C around surgeries or bleeding might be considered. Research is
      needed to study this further.

PMID- 29458234
TI  - Ultrasonographic anatomy of reproductive female leopard geckos (Eublepharis
      macularius).
AB  - Captive leopard geckos (Eublepharis macularius) often present to the exotic
      clinic for gastrointestinal impactions, follicular stasis, or dystocia. To our
      knowledge, normal ultrasonographic anatomy of these lizards has not been
      described. The objectives of this prospective, anatomic, analytical study were to
      develop ultrasound techniques for this species and to describe the normal
      sonographic anatomy of the head, coelomic cavity, and tail. Eleven, healthy,
      female leopard geckos were included. A linear array 13-18 MHz transducer was
      used. Geckos were sedated and restrained in dorsal recumbency for coelomic
      structure examination and in ventral recumbency for head and tail examinations.
      Sagittal and transverse images were acquired and authors recorded qualitative and
      quantitative ultrasonographic characteristics of anatomic structures. The ventral
      surface of the lungs, liver, gallbladder, caudal vena cava, portal vein, ventral
      abdominal vein, aorta, ovarian follicles, fat bodies, tail, and brain were
      visualized in 10 of 11 individuals. In one individual, molt precluded
      ultrasonographic examination. The heart, kidneys, urinary bladder, spleen, and
      pancreas were not visualized. The digestive tract was observed in 10 individuals
      but was too small to be measured. Findings from the current study could be used
      as a reference for future studies of leopard geckos.

PMID- 29458235
TI  - Altered cortical development in fetuses with isolated nonsevere ventriculomegaly
      assessed by neurosonography.
AB  - OBJECTIVES: To perform a comprehensive assessment of cortical development in
      fetuses with isolated nonsevere ventriculomegaly (INSVM) by neurosonography.
      METHODS: We prospectively included 40 fetuses with INSVM and 40 controls. INSVM
      was defined as atrial width between 10.0 and 14.9 mm without associated
      malformation, infection, or chromosomal abnormality. Cortical development was
      assessed by neurosonography at 26 and 30 weeks of gestation measuring depth of
      selected sulci and applying a maturation scale from 0 (no appearance) to 5
      (maximally developed) of main sulci and areas. RESULTS: INSVM showed
      underdeveloped calcarine and parieto-occipital sulci. In addition, significant
      delayed maturation pattern was also observed in regions distant to ventricular
      system including Insula depth (controls 30.8 mm [SD 1.7] vs INSVM 31.7 mm [1.8];
      P = .04), Sylvian fissure grading (>2 at 26 weeks: controls 87.5% vs INSVM 50%, P
      = .01), mesial area grading (>2 at 30 weeks: controls 95% vs INSVM 62.5%; P =
      .03), and cingulate sulcus grading (>2 at 30 weeks: controls 100% vs INSVM 80.5%;
      P = .01). CONCLUSIONS: Fetuses with INSVM showed underdeveloped cortical
      maturation including also regions, where effect of ventricular dilatation is
      unlikely. These results suggest that in a proportion of fetuses with INSVM,
      ventricular dilation might be related with altered cortical architecture.

PMID- 29458236
TI  - Medical Travel among Non-Seoul Residents to Seek Prostate Cancer Treatment in
      Medical Facilities of Seoul.
AB  - Purpose: This study aims to investigate the trend in medical travel by non-Seoul
      residents to Seoul for treatment of prostate cancer and also to investigate the
      possible factors affecting the trend. Materials and Methods: This study
      represents a retrospective cohort study using data from the Korean National
      Health Insurance System (KNHI) from 2002 to 2015. Annual trends were produced for
      proportions of patients who traveled according to the age group, economic status
      and types of treatment. Multiple logistic analysis was used to determine factors
      affecting surgeries at medical facilities in Seoul among the non-Seoul residents.
      Results: A total of 68,543 patients were defined as newly diagnosed prostate
      cancer cohorts from 2005 to 2014. The proportion of patients who traveled to
      Seoul for treatment, estimated from cases with prostate cancer-related claims,
      decreased slightly over nine years (28.0 at 2005 and 27.0 at 2014, p=0.02). The
      average proportion of medical travelers seeking radical prostatectomy increased
      slightly but the increase was not statistically significant (43.1 at 2005 and
      45.4 at 2014, p=0.26). Income level and performance of robot-assisted radical
      prostatectomy were significant positive factors for medical travel to medical
      facilities in Seoul. Combined comorbidity diseases and year undergoing surgery
      were significant negative factors for medical travel to medical facilities in
      Seoul. Conclusion: The general trend of patients travelling from outside Seoul
      for prostate cancer treatment decreased from 2005 to 2014. However, a large
      proportion remained irrespective of direct distance from Seoul.

PMID- 29458237
TI  - Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus
      Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously
      Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01).
AB  - Purpose: We investigated whether irinotecan plus capecitabine improved
      progression-free survival (PFS) compared with capecitabine alone in patients with
      human epidermal growth factor 2 (HER2) negative and anthracycline and taxane
      pretreated metastatic breast cancer (MBC). Materials and Methods: A total of 221
      patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and
      capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250
      mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS.
      Results: There was no significant difference in PFS between the combination and
      monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95%
      confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative
      breast cancer (TNBC, n=90), the combination significantly improved PFS (median,
      4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective
      response rate was numerically higher in the combination arm, though it failed to
      reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did
      not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While
      grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs 9.0%),
      hand-foot syndrome was more often observed in capecitabine arm. Quality of life
      measurements in global health status was similar. However, patients in the
      combination arm showed significantly worse symptom scales especially in
      nausea/vomiting and diarrhea. Conclusion: Irinotecan plus capecitabine did not
      prove clinically superior to single-agent capecitabine in anthracycline- and
      taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups
      differed but were manageable. The role of added irinotecan in patients with TNBC
      remains to be elucidated.

PMID- 29458239
TI  - Transmission of Helicobacter pylori.
AB  - The exact modes and routes of transmission of Helicobacter pylori (H. pylori)
      infection remain unproven. Studies showed that H. pylori bacteria can spread
      directly from one person to the other, or indirectly from an infected person to
      the environment. Presently, interpersonal pathways are more probable than
      environmental exposure routes. Person to person transmission can be mainly fecal
      oral or oral-oral. In the last 30 years many authors have investigated the main
      potential sources of H. pylori infections, vectors and risk factors for both
      fecal-oral and oral-oral routes of transmission, eating of contaminated food,
      drinking of contaminated water, and exposure to animals. They have tried to
      isolate H. pylori from feces, saliva, dental plaque. These aspects are the basis
      for the effective prevention of both H. pylori acquisition and gastroduodenal
      pathology associated with it. These issues will be discussed in this narrative
      review.

PMID- 29458238
TI  - Active contour configuration model for estimating the posterior ablative margin
      in image fusion of real-time ultrasound and 3D ultrasound or magnetic resonance
      images for radiofrequency ablation: an experimental study.
AB  - PURPOSE: The purpose of this study was to evaluate the accuracy of an active
      contour model for estimating the posterior ablative margin in images obtained by
      the fusion of real-time ultrasonography (US) and 3-dimensional (3D) US or
      magnetic resonance (MR) images of an experimental tumor model for radiofrequency
      ablation. METHODS: Chickpeas (n=12) and bovine rump meat (n=12) were used as an
      experimental tumor model. Grayscale 3D US and T1-weighted MR images were pre
      acquired for use as reference datasets. US and MR/3D US fusion was performed for
      one group (n=4), and US and 3D US fusion only (n=8) was performed for the other
      group. Half of the models in each group were completely ablated, while the other
      half were incompletely ablated. Hyperechoic ablation areas were extracted using
      an active contour model from real-time US images, and the posterior margin of the
      ablation zone was estimated from the anterior margin. After the experiments, the
      ablated pieces of bovine rump meat were cut along the electrode path and the cut
      planes were photographed. The US images with the estimated posterior margin were
      compared with the photographs and post-ablation MR images. The extracted contours
      of the ablation zones from 12 US fusion videos and post-ablation MR images were
      also matched. RESULTS: In the four models fused under real-time US with MR/3D US,
      compression from the transducer and the insertion of an electrode resulted in
      misregistration between the real-time US and MR images, making the estimation of
      the ablation zones less accurate than was achieved through fusion between real
      time US and 3D US. Eight of the 12 post-ablation 3D US images were graded as good
      when compared with the sectioned specimens, and 10 of the 12 were graded as good
      in a comparison with nicotinamide adenine dinucleotide staining and
      histopathologic results. CONCLUSION: Estimating the posterior ablative margin
      using an active contour model is a feasible way of predicting the ablation area,
      and US/3D US fusion was more accurate than US/MR fusion.

PMID- 29458240
TI  - Benign and malignant gastroduodenal diseases associated with Helicobacter pylori:
      a narrative review and personal remarks in 2018.
AB  - The subject of Helicobacter pylori continues to elicit worldwide interest in many
      research fields. Epidemiological data suggest that the prevalence of the
      infection is decreasing in Western/developed countries and even in some
      developing regions, but this is masked by the high prevalence in the most
      populous regions. Chronic gastritis, caused invariably by the bacterium, was
      again classified in Kyoto and Helicobacter pylori-associated gastritis was
      included as a distinct entity. The prevalence of peptic ulcers is decreasing, but
      bleeding ulcers are a challenging problem, with stable mortality levels even in
      the endoscopic era. With the extended use of endoscopy, gastric polyps (GP) have
      become more prevalent: some are associated with the infection, some are not.
      Autoimmune and Helicobacter-induced gastritis can share common pathogenetic
      mechanisms. Gastric cancer (GC) is ranked highly on mortality lists worldwide.
      Its surgical treatment has registered some progress though. Little, if any
      improvement has been achieved in the medical treatment of advanced GC. With
      proper organization, GC seems a preventable disease. In spite of many guidelines,
      the Pan-European registry of Helicobacter pylori management shows that
      eradication rates obtained in many places are suboptimal. A new therapeutic
      regimen was compiled with promising pilot results. The results obtained with
      vonaprazan are limited to Asia. New avenues of both antibiotic and non-antibiotic
      treatments are expected to accelerate the eradication of this ulcerogenic and
      carcinogenic bacterium.

PMID- 29458241
TI  - Management of Helicobacter pylori in Piedmont, Italy.
AB  - Helicobacter pylori (H. pylori) is a Gram-negative bacterium, usually acquired
      during childhood, whose natural habitat is the gastric lumen. H. pylori is
      accepted as the most important cause of gastritis and peptic ulcer in humans.
      Nevertheless, its important role in the pathogenesis of gastric cancer as well as
      in several extra-gastroduodenal diseases has been confirmed. The aim of this work
      is to discuss, for the first time in a single article, all publications
      concerning H. pylori infection arising from Piedmont region, Italy, where in 1893
      Giulio Bizzozero was the first who observed and described spiral organisms in the
      stomach of animal models. A systematic review of all publications on the
      management of H. pylori in adults in Piedmont, based on a PubMed and a Scopus
      research from 1965 to 2017 was performed. The discussed aspects are the
      epidemiology, the study on gastric and extragastric diseases related to H.
      pylori, the diagnostic methods, the treatment of H. pylori infection, and the
      possibility of reinfection. In conclusions, with almost 70 publications, Piedmont
      has proudly maintained the tradition of the father of the H. pylori.

PMID- 29458242
TI  - Prolonged-release oxycodone-naloxone for pain management in advanced EGFR wild
      type lung cancer patients.

PMID- 29458243
TI  - Mild-to-moderate hemoptysis: a diagnostic and clinical challenge.
AB  - Mild-to-moderate hemoptysis is defined as the expectoration of blood or blood
      streaked sputum originating from the lower respiratory tract, in volumes that do
      not immediately threaten the patient's life. Nevertheless, it is a very common
      respiratory symptom and the list of underlying respiratory or non-respiratory
      diseases is vast, ranging from the most worrying to more easily manageable
      etiologies. In this narrative review, we have analyzed the most recent
      recommendations inferred from the literature, in terms of diagnostic as well as
      therapeutic approach.

PMID- 29458244
TI  - Clinical and molecular characteristics of pulmonary sarcomatoid carcinoma.
AB  - Background/Aims: Pulmonary sarcomatoid carcinoma (PSC) is a poorly differentiated
      non-small cell lung cancer (NSCLC) that contains components of spindle or giant
      cells. Owing to its low prevalence, there are insufficient data regarding its
      clinical features, therapeutic strategies and prognosis. METHODS: The medical
      records of 26 patients diagnosed with PSC from January 2009 to June 2015 were
      reviewed and analyzed for clinicopathological characteristics, treatment
      modality, and outcomes. RESULTS: The median age was 69.5 years. Twenty-three
      patients (88%) were male. Twenty-four patients (92%) were smokers. The median
      time from symptom onset to diagnosis was one month. Eighteen patients (69%) were
      diagnosed at an advanced stage. Pleomorphic carcinoma was the most common
      subtype, and epidermal growth factor receptor (EGFR) mutation was positive in two
      of 11 patients. Among 13 patients tested for programmed death ligand 1 (PD-L1)
      immunohistochemistry assay, eight showed high expression of PD-L1. The median
      overall survival (OS) of all patients was 9.5 months. In total, 12 patients were
      treated with chemotherapy: nine with platinum-based doublet therapy, two with
      tyrosine kinase inhibitor, and one with docetaxel. Seven patients showed partial
      response or stable disease. The median OS and progression-free survival of
      patients who received chemotherapy were 8.7 and 2.8 months, respectively.
      Conclusions: PSC was more common in males, smokers, and the elderly, with worse
      prognosis than ordinary NSCLC; chemotherapy response was favorable, and EGFR
      mutation status and PD-L1 expression may offer more therapeutic options.

PMID- 29458245
TI  - Impact of sleep quality on clinical features of primary Sjogren's syndrome.
AB  - Background/Aims: This study aimed to investigate the inf luence of poor sleep
      quality on clinical features of primary Sjogren's syndrome (pSS). Methods: Sleep
      quality was cross-sectionally assessed using the Pittsburgh Sleep Quality Index
      (PSQI), and demographic, clinical, and laboratory data were collected from 115
      Korean patients with pSS. The patients completed questionnaires on the European
      League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI), quality of
      life (EuroQOL five dimensions questionnaire [EQ-5D]), fatigue (fatigue severity
      score [FSS]), and depression (Beck Depression Inventory [BDI] II]). Symptoms and
      patient global assessment (PGA) were evaluated with a 100-mm visual analogue
      scale (VAS). The EULAR sicca score (ESS), ESSPRI, and EULAR SS Disease Activity
      Index (ESSDAI) were calculated at study enrollment. Results: Fifty-three patients
      (46.1%) had poor sleep quality and 32.4% of 71 patients without depression were
      poor sleepers. Poor sleepers had a significantly lower EQ-5D or ESSDAI and a
      significantly higher FSS, BDI-II, PGA, ESS, ESSPRI, or VAS scores for extra
      glandular symptoms than good sleepers. Neutrophil and lymphocyte counts were
      significantly higher and immunoglobulin G levels tended to decrease in poor
      sleepers. Additionally, PSQI was negatively correlated with EQ-5D and ESSDAI and
      positively with ESS, FSS, BDI-II, PGA, VAS scores for their symptoms, and ESSPRI.
      Multivariate analysis revealed that poor sleep quality remained the independent
      determinants of the unsatisfactory symptom state (ESSPRI >= 5). Conclusions: Our
      results showed that poor sleep quality could significantly affect the patient
      oriented outcomes and physician-reported activity index of pSS patients through
      the various effects of sleep quality on the psychological or somatic symptoms and
      the immune system.

PMID- 29458246
TI  - Antiplatelet therapy in STEMI undergoing primary PCI: when, which one and how
      long.
AB  - Reperfusion therapy for patients presenting with an acute ST-segment elevation
      myocardial infarction (STEMI) involves primary percutaneous coronary intervention
      (PPCI) and concomitant dual antiplatelet therapy (DAPT) with combination of a
      P2Y12 inhibitor and acetylsalicylic acid (ASA). Decision regarding DAPT can be
      challenging clinically in the modern era with the evolution of newer stents, more
      potent antiplatelet agents and novel anticoagulant drugs in addition to an older
      patient population with multiple comorbidities. This review outlines the
      currently available antiplatelet treatments, and their place within the
      therapeutic timeline of a patient presenting with STEMI.

PMID- 29458247
TI  - Magic Touch(r): preliminary clinical evidence with a novel sirolimus drug coated
      balloon.
AB  - Drug-coated balloons (DCB) have been developed in recent years to overcome some
      of the drug-eluting stents limitations. There is an established indication for
      the use of DCB in the treatment of in-stent restenosis and they are also variably
      used in various setting, in particular small coronary vessels and bifurcations.
      Until 2016, all DCBs available in Europe eluted paclitaxel, a highly lipophilic
      drug with narrow therapeutic window. In April 2016 a new sirolimus-coated balloon
      (Magic Touch(r), Envision Scientific PVT, Bhatpore, India) obtained the CE Mark.
      This device shares a new-generation delivery system and is able to release in a
      few seconds an effective dosage of sirolimus.

PMID- 29458248
TI  - Revascularization strategies in STEMI with multivessel disease: when and how.
AB  - Acute ST-segment elevation myocardial infarction (STEMI) typically arises from
      total occlusion of an epicardial coronary artery, most often due to
      atherosclerotic plaque rupture/erosion and subsequent thrombus formation. Granted
      this, important angiographic information for patients presenting with STEMI is
      not only about the status of infarct-related artery (IRA) but also about the
      atherosclerotic disease burden and disease severity of non-IRA vessels. Previous
      studies have reported that multivessel coronary artery disease is found in
      approximately 50% of patients with STEMI undergoing primary percutaneous coronary
      intervention (PCI). Primary PCI is now considered the gold standard in the
      treatment for patients with STEMI; however, the optimal reperfusion strategy in
      patients with STEMI and multivessel disease (MVD) remains uncertain. In this
      review, we summarize the available evidence on treatment options for patients
      with STEMI and MVD and highlight current guideline recommendations on this topic.

PMID- 29458249
TI  - Risk stratification in secondary cardiovascular prevention.
AB  - Although a substantial reduction in post-myocardial infaction mortality has been
      obtained in recent decades, one-year mortality rates are still high and 20% of
      patients who survive after the acute phase suffer a second cardiovascular event
      in the first year. In the setting of secondary cardiovascular prevention, the
      long-term cardiovascular risk stratification represents one of the most
      interesting and charming challenge for physician. Lifestyle changes and long-term
      control of traditional cardiovascular risk factors remain the cornerstone of
      secondary cardiovascular prevention and continue to offer the most powerful
      prognostic implications in the field of preventive cardiology with strong
      evidence of reduction in mortality and morbidity. In this regard, clinical, ECG,
      echocardiographic, cardiopulmonary exercise test data as well as biochemical
      markers of adverse prognosis are useful tool to identify patients at risk of
      developing future cardiovascular events. An integrated approach based on the
      analysis of all cardiovascular risk factors (traditional and emerging) along with
      instrumental and laboratory data represents the better way to predict prognosis
      in secondary cardiovascular prevention.

PMID- 29458250
TI  - Enantioselective Intermolecular [2+2] Photocycloaddition Reaction of Cyclic
      Enones and Its Application in a Synthesis of (-)-Grandisol.
AB  - The intermolecular [2+2] photocycloaddition of typical cyclic alpha,beta
      unsaturated enones, such as 2-cyclohexenone, with olefins was performed in
      moderate to good yields (42-82%) and with high enantioselectivity (82%-96% ee).
      An unusual substitution pattern at the chiral oxazaborolidine-AlBr3 Lewis acid
      complex that promotes the reaction was found to be crucial for the success of the
      reaction. The method was applied to the enantioselective synthesis of the
      monoterpene (-)-grandisol, which could be accomplished in six steps and with an
      overall yield of 13% starting from 3-methyl-2-cyclohexenone.

PMID- 29458251
TI  - Pushing Nonlinear Optical Oxides into the Mid-Infrared Spectral Region Beyond 10
      MUm: Design, Synthesis, and Characterization of La3SnGa5O14.
AB  - Mid-infrared (mid-IR) coherent light is crucial for several applications in
      science as well as daily life, and its development especially in powerful
      augmentation is constrained by the availability of nonlinear optical (NLO)
      materials. The development of useful mid-IR NLO materials is limited by the
      requirements of a wide mid-IR transparent window, high laser damaged threshold
      (LDT), and strong NLO effect. It is common knowledge that oxides are not suitable
      mid-IR NLO materials, as their IR absorption cutoff wavelengths are usually <6
      MUm; however, their LDTs and NLO effects can be large. Herein, we focused on
      langasite oxides and built structure-composition-property maps that describe the
      NLO properties in these materials by combining computational property prediction
      and experimental characterization. Accordingly, rational molecular design was
      performed, a new member of the langasite family, La3SnGa5O14 (LGSn), was
      synthesized, and single crystals were grown. The produced material exhibits the
      widest transparent region (0.27-11.0 MUm) among available oxides, the largest LDT
      (846 MW/cm2) among materials that are transparent to 10 MUm, and the strongest
      SHG effect among langasites. The discovery of LGSn facilitates the application of
      oxides as NLO crystals in the mid-IR spectral region beyond 10 MUm. More
      generally, the developed strategy could be used to guide and accelerate the
      systematic discovery of functional materials through understanding the key
      structure-composition-property relationships using the predictive power of
      computational tools.

PMID- 29458252
TI  - Selective Sensing and Imaging of Penicillium italicum Spores and Hyphae Using
      Carbohydrate-Lectin Interactions.
AB  - The blue-green mold Penicillium italicum is among the most problematic post
      harvest plant infections limiting the integrity of citrus and many other crops
      during storage and transportation, but there is no sensor for its on-site or
      field detection. We hereby, for the first time, report the development of novel
      biomolecular sensor for assessing the presence of P. italicum spores and hyphae
      using carbohydrate-lectin recognitions. Two approaches were developed: (i)
      lateral tests using standalone poly(amic) acid (PAA) membranes and glass surfaces
      and (ii) quantitative tests on 96-well polystyrene plates and paper electrodes.
      In both cases, the surfaces were functionalized with novel derivatized sugar
      based ligands while staining was performed with gold nanoparticles. Both
      approaches provided strong signals for 104 spores/mL of P. italicum isolated from
      experimentally infected lemons as the lowest-reliable concentration. The 96-well
      plate-based gave the most sensitive detection with a 4 * 102 spores/mL limit of
      detection, a linear dynamic range between 2.9 * 103 and 6.02 * 104 spores/mL ( R2
      = 0.9939) and standard deviation of less than 5% for five replicate measurements.
      The selectivity of the ligands was tested against Trichaptum biforme, Glomerulla
      cingulata ( Colletotrichum gloeosporioides), and Aspergillus nidulans fungi
      species. The highest selectivity was obtained using the sugar-based gold
      nanoparticles toward both the spores and the hyphae of P. italicum. The advanced
      specificity was provided by the utilized sugar ligands employed in the synthesis
      of gold nanoparticles and was independent from size and shapes of the AuNPs.
      Accuracy of the sensor response showed dramatic dependence on the sample
      preparation. In the case of 5-10 min centrifugation at 600 rpm, the spores can be
      isolated free from hyphae and conidiophore, for which spiked recovery was up to
      95% (std +/-4). In contrast, for gravity-based precipitation of hyphae, the
      spiked recovery was 88% (std 11).

PMID- 29458253
TI  - Structure and Dynamics of Zr6O8 Metal-Organic Framework Node Surfaces Probed with
      Ethanol Dehydration as a Catalytic Test Reaction.
AB  - Some metal-organic frameworks (MOFs) incorporate nodes that are metal oxide
      clusters such as Zr6O8. Vacancies on the node surfaces, accidental or by design,
      act as catalytic sites. Here, we report elucidation of the chemistry of Zr6O8
      nodes in the MOFs UiO-66 and UiO-67 having used infrared and nuclear magnetic
      resonance spectroscopies to determine the ligands on the node surfaces
      originating from the solvents and modifiers used in the syntheses and having
      elucidated the catalytic properties of the nodes for ethanol dehydration, which
      takes place selectively to make diethyl ether but not ethylene at 473-523 K.
      Density functional theory calculations show that the key to the selective
      catalysis is the breaking of node-linker bonds (or the accidental adjacency of
      open/defect sites) that allows catalytically fruitful bonding of the reactant
      ethanol to neighboring sites on the nodes, facilitating the bimolecular ether
      formation through an SN2 mechanism.

PMID- 29458254
TI  - The ACS Measurement Journals, the Analytical Division, and Pittcon 2018: A Busy
      Four Days.

PMID- 29458255
TI  - Intermetallic Chemistry: New Advances in Humanity's Age-Old Exploration of Metals
      and Alloys.

PMID- 29458256
TI  - Knowledge, attitude and practices on diabetes, hypertension and diabetic
      retinopathy and the factors that motivate screening for diabetes and diabetic
      retinopathy in a pyramidal model of eye health care.
AB  - INTRODUCTION: To report the results of a knowledge, attitude and practice (KAP)
      study related to diabetes mellitus (DM), hypertension and diabetic retinopathy
      (DR) of patient populations in India at different levels (Tertiary (T), Secondary
      (S) and Primary (P)) of a pyramidal model of eye health care. METHODS: In total,
      202 participants, composed of equal numbers of diabetic and non-diabetic patients
      at a Tertiary urban facility (T), a Secondary rural facility (S) and a Primary
      (P) community-screening program, were surveyed on their knowledge, knowledge
      sources, attitudes, practices and factors that motivate use of eye health
      services. RESULTS: People with diabetes had a higher mean knowledge and attitude
      score about DM, hypertension and DR (67.3% T, 59.4% S, 47.0% P) than non
      diabetics (41.8% T, 29.0% S, 23.5% P; p<0.001). Awareness of DR was more 65.3%
      among diabetics compared with 22.0% among non-diabetics at all locations. Most
      participants in all locations were aware of hypertension (84.0% T, 65.3% S, 52.9%
      P), but few knew it could affect the eyes (30.0% T, 12.2% S, 13.7% P) or be
      associated with diabetic complications (30.0% T, 32.7% S, 21.8% P). Many
      participants had never previously had a dilated eye examination (2% T, 40% S, 50%
      P). Participants were motivated to visit an eye facility for a routine checkup
      (70.6%), poor vision (22.6%) or a glucose/blood pressure test (17.7%) at a
      Primary-level facility and for follow-up or poor vision at the other facilities
      (28% and 42% Tertiary, 50% and 30% Secondary). CONCLUSION: Practice-oriented
      education and advertising of facilities tailored for the relevant populations at
      each level of an eye health pyramid and continuation of fundus, glucose and blood
      pressure screening programs can help in creating awareness about diabetes,
      hypertension and diabetic retinopathy.

PMID- 29458257
TI  - Recruiting and Retaining Patient-Caregiver-Nurse Triads for Qualitative Hospice
      Cancer Pain Research.
AB  - BACKGROUND: Qualitative pain research for hospice patients with cancer and their
      caregivers involves recruiting and retaining participants with multiple
      vulnerabilities and ethical and logistical challenges. These have been reported
      for studies of individuals or dyads. However, there are no reports of the related
      challenges and outcomes where the sampled population was a hospice triad.
      OBJECTIVES: Qualitative research about pain management for home hospice patients
      with cancer contributes rich descriptive data and such studies are critical to
      improving cancer pain outcomes. We describe the ethical and pragmatic challenges
      we faced in a study of the hospice caring triad, operationalized as the patient,
      family caregiver, and nurse; how our study design anticipated them; and related
      outcomes. RESULTS: We found that having an established relationship with the
      hospice agency at which we recruited participants, clearly identifying potential
      participants at the onset of hospice care, practice using a recruitment script,
      patient recruitment of caregivers, establishing rapport, and participants
      determining when interviews should end helped us recruit and retain our sample.
      We were unable to accrue our anticipated triad sample, partially because of nurse
      gatekeeping and the condition at admission of patient participants who enrolled
      but had physical decline or died prior to written consent. CONCLUSIONS: Although
      researchers will always face challenges to enrolling individuals and groups in
      cancer pain studies, with careful study design, recruitment, and retention
      planning and research team-participant engagement, it is possible to gather a
      robust corpus of qualitative data.

PMID- 29458258
TI  - Broken bridges-new school transitions for students with autism spectrum disorder:
      A systematic review on difficulties and strategies for success.
AB  - Transitioning to a new school is often challenging for students with autism
      spectrum disorder. Few studies have examined the transition needs of students
      with autism spectrum disorder or the benefits of specific supports. This review
      synthesizes research findings on the difficulties that school transitions pose
      for students with autism spectrum disorder and their parents and teachers, and
      the strategies used to support students and parents during school transition. The
      review included 27 studies (10 examining the transition to primary school, 17 the
      transition to secondary school), with data from 443 students with autism spectrum
      disorder, 453 parents, and 546 teachers, across four continents (North America,
      Europe, Africa, and Australia). Studies reported that children with autism
      spectrum disorder struggled with anxiety and increased social pressure, their
      parents felt overwhelmed with complex placement decisions and worried about the
      well-being of their children, and teachers strove to provide appropriate supports
      to their students with autism spectrum disorder, often with inadequate resources.
      Findings indicated that the most useful strategies involved helping the student
      adjust to the new school setting, individualizing transition supports, clarifying
      the transition process for parents, and fostering communication both between the
      sending and receiving schools, and school and home.

PMID- 29458262
TI  - Time to go beyond observing the problem. Response to: Dying in hospital:
      socioeconomic inequality trends in England, DOI: 10.1177/1355819616686807.

PMID- 29458263
TI  - Comparative study of nano and bulk Fe3O4 induced oxidative stress in Wistar rats.
AB  - CONTEXT: Magnetic nanomaterials (Fe3O4 NMs) have become novel tools with multiple
      biological and medical applications because of their biocompatibility. However,
      adverse health effects of these NMs are of great interest to learn. OBJECTIVE:
      This study was designed to assess the size and dose-dependent effects of Fe3O4
      NMs and its bulk on oxidative stress biomarkers after post-subacute treatment in
      female Wistar rats. METHODS: Rats were daily administered with 30, 300 and 1000
      mg/kg b.w. doses for 28 d of Fe3O4 NMs and its bulk for biodistribution and
      histopathological studies. RESULTS: Fe3O4 NMs treatment caused significant
      increase in lipid peroxidation levels of treated rats. It was also observed that
      the NM treatment elicited significant changes in enzyme activities of superoxide
      dismutase, catalase, glutathione peroxidase, glutathione reductase  and
      glutathione-S-transferase in treated rat organs with major reduction in
      glutathione content. Metal content analysis revealed that tissue deposition of NM
      in the organs was higher when compared to bulk and caused histological changes in
      liver. CONCLUSION: This study demonstrated that for same dose, NM showed higher
      bioaccumulation, oxidative stress and tissue damage than its bulk. The difference
      in toxic effect of Fe3O4 nano and bulk could be related to their altered
      physicochemical properties.

PMID- 29458264
TI  - The experience and management of HIV stigma among HIV-negative adults in
      heterosexual serodiscordant relationships in New York City.
AB  - Despite treatment advances that have improved the health and life expectancy of
      HIV-positive people and contribute to the prevention of HIV transmission, HIV
      stigma is still frequently experienced by HIV-infected individuals and those
      close to them. This study investigated the types of HIV-related stigma
      experienced by HIV-negative adults in serodiscordant heterosexual relationships
      when their partner's HIV-positive status was revealed to family and friends and
      their strategies to manage such stigma. In-depth interviews were conducted in New
      York City with 56 men and 44 women who were HIV negative and had been in a
      relationship for at least six months with an HIV-positive partner of the opposite
      sex. Those who had disclosed the HIV status of their partner to family or friends
      experienced four main types of stigmatizing behaviours: distancing (avoidance of
      the participant or his/her partner for fear of infection), depreciation of the
      partner (being told their partner is not worthy of them), violation of privacy
      (people spreading the information that the partner is HIV positive), or
      accusations (being told that it was wrong to be in a relationship with HIV
      positive people or to try to conceive with them). Participants described four
      main ways of managing actual or anticipated stigma: secrecy (not disclosing the
      HIV status of their partner to anyone), avoidance (breaking ties with people who
      held stigmatizing views), seeking support from their partner or the HIV-positive
      community (e.g., HIV-related organizations or their partner's family or friends),
      or education (informing family or friends about HIV treatment and prevention).
      Findings show that HIV-related "courtesy" stigma is frequently experienced by HIV
      negative people in serodiscordant relationships but often can be managed.
      Offering support to individuals in serodiscordant relationships can improve the
      quality of life of HIV-positive people and their HIV-negative partners and
      potentially reduce HIV stigma.

PMID- 29458265
TI  - Clean intermittent catheterization rates after initial and subsequent treatments
      with onabotulinumtoxinA for non-neurogenic overactive bladder in real-world
      clinical settings.
AB  - OBJECTIVE: Previous randomized controlled trials have reported a 6.1-6.9%
      incidence of clean intermittent catheterization (CIC) following treatment with
      onabotulinumtoxinA in non-neurogenic overactive bladder (OAB) patients who were
      inadequately managed by >=1 anticholinergic. A multi-center retrospective chart
      review assessed the real-world rate of voiding dysfunction requiring
      catheterization. METHODS: Patients received onabotulinumtoxinA 100 U (approved
      dose) administered by experienced injectors between January 2013 and June 2015.
      Patients using CIC or an indwelling catheter for >=24 hours for voiding
      dysfunction prior to onabotulinumtoxinA injections were excluded. The primary
      outcome was post-treatment CIC (lasting >24 hours; per individual physician's
      clinical judgment considering patient's voiding symptoms, post-void residual
      [PVR] urine volumes and patient bother). Potential baseline predictors of CIC
      (history of pelvic prolapse, cystocele, diabetes, PVR urine volume and age) were
      assessed using multivariable logistic regression. RESULTS: Overall, 299 patients
      received their first treatment with onabotulinumtoxinA 100 U. Mean age was 66.4
      years; 98.3% were female. The incidence of CIC was 2.7% in the total study
      population after the first treatment with onabotulinumtoxinA. The de novo CIC
      rate in treatments 2 and 3 combined was similarly low (3.2%). None of the
      evaluated baseline characteristics were significant predictors of CIC initiation
      due to the low CIC incidence. CONCLUSIONS: This real-world study of non
      neurogenic OAB patients treated with onabotulinumtoxinA suggests that the CIC
      rate is lower than the rates reported in previous studies. There were no
      significant correlations between baseline predictors and CIC initiation, although
      statistical significance may not have been reached because of the low incidence
      of CIC.

PMID- 29458266
TI  - Acrylic acid grafted tamarind kernel polysaccharide-based hydrogel for bone
      tissue engineering in absence of any osteo-inducing factors.
AB  - PURPOSE: With increased life expectancy, disorders in lifestyle and other
      clinical conditions, and the changes in the connective tissues such as in bone,
      impose diverse biomedical problems. Cells belong to osteogenic lineages are
      extremely specific for their surface requirements. Therefore, suitable surfaces
      are the critical bottle neck for successful bone tissue engineering. This study
      involves assessment of polysaccharide-based hydrogel which effectively allows
      growth, differentiation and mineralisation of osteogenic cells even in the
      absence of osteogenic inducing factors. MATERIALS AND METHODS: Tamarind Kernel
      Polysaccharide was grafted with acrylic acid at different mole ratio. The
      critical parameter, surface morphology for bio application was assessed by SEM.
      MTT assay has been performed with hydrogels on Saos-2 cells. The biocompatibility
      and adhesion of different cell lines (F-11, Saos-2, Raw 264.7 and MSCs) on
      hydrogel surface was performed by Phalloidin and DAPI staining. Further the
      differentiation, mineralization and expression of different osteogenic markers,
      ALP assay, Alizarin Red staining and q-PCR was performed. RESULTS: The hydrogels
      show highly porous and interconnected pores. MTT assay demonstrates the hydrogel
      have no cytotoxicity towards Saos-2 cells and are suitable for proliferation of
      different lineage of cell lines. ALP, Alizarin red staining and q-PCR assay shows
      that the hydrogel surface enhances the differentiation, mineralization and
      expression of different osteogenic genes in Saos-2 cells in the absence of any
      osteogenic inducing factors. Conclusion Synthesized hydrogel surface triggers
      signalling events towards osteogenesis even in the absence of added growth
      factors. We proposed that this material can be used for effective bone tissue
      engineering in vitro at low cost.

PMID- 29458267
TI  - Can self-affirmation exacerbate adverse reactions to stress under certain
      conditions?
AB  - OBJECTIVE: Self-affirmation has repeatedly been shown to reduce adverse
      psychological and physiological responses to stress. However, it is plausible
      that self-affirmation could exacerbate negative reactions to stress under certain
      conditions. The current research explored whether self-affirmation would increase
      negative psychological responses to a stressor occurring in a central life domain
      characterised by low levels of control. DESIGN: Female participants (Study 1 N =
      132; Study 2 N = 141) completed baseline measures of anxiety and mood. They were
      then randomly allocated to complete a self-affirmation or control task, before
      reading a narrative documenting a stressful birth and imagining themselves in the
      place of the woman giving birth. After completing this task, participants again
      reported their levels of anxiety and positive mood. MAIN OUTCOME MEASURES:
      Anxiety and positive mood assessed at follow-up. RESULTS: Study 1 demonstrated
      that self-affirmed women experienced increased anxiety and less positive mood at
      follow-up, compared both to baseline and to women in the control condition. Study
      2 revealed that the effect of self-affirmation on outcomes was moderated by fear
      of childbirth. CONCLUSION: These results provide preliminary evidence that self
      affirmation may worsen negative responses to stressors under certain conditions
      and for certain individuals.

PMID- 29458268
TI  - PLHIV are more likely to have mental distress: evidence from a comparison of a
      cross-section of HIV and diabetes patients at Tertiary Hospitals in Nigeria.
AB  - : HIV is now regarded as a chronic disease because of the availability of
      treatment. However, it is not well known if there are differences (clinically and
      in magnitude) between the mental health status of PLHIV and people living with
      other chronic diseases. The aim of this study was to compare the mental health
      status of patients attending antiretroviral clinics to patients attending
      diabetes clinics at tertiary hospitals in Ogun State, Nigeria. A comparative
      hospital-based cross-sectional study of mental distress among 639 HIV-positive
      and 639 diabetic patients was carried out. Multivariate logistic regression
      analysis was used to control for confounders and to predict the probability of
      mental distress in PLHIV. The mean age of the participants was 44.87 (+/- 13.83)
      years and it had a range of 63 years (17 to 80). The prevalence of mental
      distress was higher among HIV-positive participants (46.79%) than diabetic
      participants (33.02%) (p < 0.0001). HIV-positive participants had greater odds of
      mental distress than diabetics (odds ratio = 1.78; 95% CI = 1.41-2.25). HIV
      positivity, female sex, lower levels of education, being unemployed, poorer
      housing conditions and separated, widowed or divorced were associated with higher
      odds of mental distress (p < 0.05). Mental distress was predicted by HIV
      positivity, occupation and current marital status. HIV infection and social
      inequalities are independent risk factors for mental distress. The odds of having
      mental distress is higher among PLHIV compared with diabetic patients. Addressing
      social inequalities might be the critical factor in the control of mental
      distress among PLHIV. ABBREVIATIONS: ART: Anti-retroviral therapy; CI: Confidence
      interval; YLD: Years Lived with Disability; GHQ: General Health Questionnaire;
      HIV/AIDS: Human Immunodeficiency Virus/ Acquired Immunodeficiency Syndrome; LMIC:
      Low and middle-income countries; MH: Mantel-Haenszel; PLHIV: People living with
      HIV; ROC: Receiver operating characteristic.

PMID- 29458269
TI  - In vitro and in vivo evaluation of folate receptor-targeted a novel magnetic drug
      delivery system for ovarian cancer therapy.
AB  - Doxorubicin is widely used anticancer drug; however, use of doxorubicin is
      limited. Under externally applied magnetic field, magnetic agents can help to
      transport drug directly to tumor. Folate receptor is overexpressed in ovarian
      carcinomas. In this study, we aimed to develop magnetically responsive and folate
      receptor-targeted biomimetic drug delivery system for ovarian cancer therapy.
      Doxorubicin-loaded and glucose/gluconic acid-coated magnetic nanoparticles were
      synthesized and erythrocyte membrane vesicles were used for coating of
      nanoparticles. Folate ligand was anchored to surface so as to target receptor.
      Hydrodynamic size of nanocarrier was found as 91.2 +/- 20.8 nm. The results
      showed that delivery system has controlled drug release profile and biocompatible
      features. In folate-free medium, folate receptor-targeted nanocarrier showed
      10.33-fold lower IC50 values for A2780 cells and 3.93-fold lower for OVCAR3 cells
      compared to non-targeted nanoparticles and demonstrated more cytotoxicity against
      ovarian cancer cells. Moreover, magnetically and folate receptor-targeted
      doxorubicin delivery system was significantly more effective for therapy of
      xenografted nude mice than free doxorubicin based on tumor shrinkages and
      biochemical parameters. In conclusion, it can be suggested that folate ligand
      attached and biomimetically designed magnetic drug delivery system have
      advantages and potential for targeted ovarian cancer therapy.

PMID- 29458270
TI  - The involvement of Nrf2 antioxidant signalling pathway in the protection of
      monocrotaline-induced hepatic sinusoidal obstruction syndrome in rats by (+)
      catechin hydrate.
AB  - Hepatic sinusoidal obstruction syndrome (HSOS) is a rare and life-threatening
      liver disease. (+)-Catechin is a natural dietary flavonol with high antioxidant
      capacity. This study aims to investigate the involvement of nuclear factor
      erythroid 2-related factor 2 (Nrf2) antioxidant signalling pathway in the
      protection of (+)-catechin hydrate (CAT) against monocrotaline (MCT)-induced
      HSOS. Results of serum alanine/aspartate aminotransferases (ALT/AST) activities,
      total bilirubin (TBil) and bile acids (TBA) amounts, liver histological
      observation, scanning electron microscope evaluation, and hepatic
      metalloproteinase-9 (MMP-9) expression all demonstrated the protection of CAT
      against MCT-induced HSOS in rats. CAT attenuated MCT-induced liver oxidative
      injury in rats and the formation of cellular reactive oxygen species (ROS) in
      human hepatic sinusoidal endothelial cells (HHSECs). CAT-enhanced Nrf2 nuclear
      translocation in livers from MCT-treated rats and in HHSECs treated with MCT, and
      further increased the expression of Nrf2-dependent genes including catalytic or
      modify subunit of glutamate-cysteine ligase (GCLC/GCLM), haem oxygenase-1 (HO-1)
      and NAD(P)H:quinone oxidoreductase 1 (NQO1). Moreover, GCL inhibitor L-buthionine
      (S, R)-sulfoximine (BSO), NQO1 inhibitor diminutol (Dim), and HO-1 inhibitor zinc
      protoporphyrin (ZnPP) all abrogated CAT-provided the protection against MCT
      induced cytotoxicity in HHSECs. The results of molecular docking analysis
      indicated the potential interaction of CAT with the Nrf2-binding site in kelch
      like ECH-associated protein-1 (Keap1) protein. In summary, this study
      demonstrated the critical involvement of Nrf2 antioxidant signalling pathway in
      CAT-provided the protection against MCT-induced HSOS.

PMID- 29458271
TI  - In vitro and in vivo evaluation of electrospun cellulose
      acetate/gelatin/hydroxyapatite nanocomposite mats for wound dressing
      applications.
AB  - The present study aimed to evaluate the efficacy of cellulose
      acetate/gelatin/nanohydroxyapatite (CA/Gel/nHA) nanocomposite mats as the wound
      dressing. The dressings were prepared with electrospinning of CA/Gel solutions
      containing 12.5, 25 and 50 mg nHA. The dressings were evaluated regarding their
      water uptake capacity, morphology, tensile strength, water vapour transmission
      rate, wettability and cellular response with L929 cell line. The results showed
      that the concentration of nHA had a direct correlation with porosity, water
      contact angle, water uptake, water vapor transmission rate and proliferation. In
      vivo studies showed that all dressings had higher wound closure percent than the
      sterile gauze, as the control. The highest wound closure value was achieved in
      the CA/Gel +25 mg nHA group, which showed 93.5 +/- 1.6%. The histological and the
      histomorphometric examinations of the wounds revealed that the CA/Gel +25 mg nHA
      dressing had the greatest collagen synthesis, re-epithelialization,
      neovascularization and also the best cosmetic appearance. Based on our finding,
      it could be concluded the applicability of electrospun nanofibrous CA/Gel/nHA
      dressings for successful wound treatment.

PMID- 29458272
TI  - Difference between right-sided and left-sided colorectal cancers: from embryology
      to molecular subtype.
AB  - INTRODUCTION: Colorectal cancer is one of the most common malignancies in the
      world, and it exhibits differences in incidence, pathogenesis, molecular
      pathways, and outcome depending on the location of the tumor. Differences in the
      microbiome, clinical characteristics, and chromosomal and molecular
      characteristics have been reported between the right and left side of the colon.
      Areas covered: This review focuses on the latest developments in epidemiological
      and chromosomal and molecular studies, which have enhanced our understanding on
      the underlying genetic and immunological differences between the right-sided
      colon and the left-sided colorectum in metastatic colorectal cancer. Expert
      commentary: The numerous findings regarding differences between right- and left
      sided colon cancers should have an impact on colorectal cancer screening and
      therapy. The location of the colorectal cancer should be considered before group
      stratification into genetic, clinical, and especially chemotherapy trials. A more
      tailored approach to colon cancer treatment would be highly desirable if future
      trials further support the hypothesis of two distinct tumor entities.

PMID- 29458273
TI  - Correction to: Liu et al., Multipronged ethanol ablation combined with TACE for
      intermediate hepatocellular carcinoma.

PMID- 29458274
TI  - Nutrient composition, ruminal degradability and whole tract digestibility of
      whole crop maize silage from nine current varieties.
AB  - Since maize silage is an important forage in cattle nutrition, it is important to
      know its nutritive value. Much effort is put into breeding maize, and several new
      varieties are introduced on the market every year. This requires periodical
      analyses of the nutritive value of current maize varieties for the formulation of
      cattle rations. The aim of this study was to examine the nutritive value of whole
      crop maize silage (WCMS) from nine maize varieties in 3 consecutive years. For
      the analysis of nutrient composition and ruminal degradability of organic matter
      (OM), crude protein (CP), neutral detergent fibre (aNDFom) and non-fibre
      carbohydrates (NFC), varieties were harvested at three harvest dates (50%, 55%
      and 60% dry matter content in ear). Due to capacity limitations, the
      digestibility of WCMS was tested only for the middle harvest date. The CP and
      acid detergent fibre (ADFom) content was affected (p < 0.05) while aNDFom and NFC
      content was not influenced by variety. With advancing maturity, CP, aNDFom and
      ADFom content declined while NFC content increased. Variety influenced effective
      ruminal degradability (ED) of nutrients, except for CP. The ED of all examined
      nutrients decreased as maturity advanced from first to third harvest date.
      Digestibility of OM, ADFom and NFC was significantly and digestibility of aNDFom
      was tendentially (p = 0.064) influenced by variety. Additionally, an effect of
      year and a harvest date * year interaction was found for almost all examined
      parameters. In conclusion, variety, harvest date and year influence the nutritive
      value of WCMS. A comparison with earlier studies shows that current varieties
      have a higher fibre digestibility and a slower-ripening stover compared to older
      varieties.

PMID- 29458275
TI  - Structural damage and inflammation on radiographs or magnetic resonance imaging
      are associated with cortical interruptions on high-resolution peripheral
      quantitative computed tomography: a study in finger joints of patients with
      rheumatoid arthritis and healthy subjects.
AB  - OBJECTIVES: To study the relationship between structural damage and inflammatory
      features on magnetic resonance imaging (MRI) or radiography and other risk
      factors [anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF)
      seropositivity, hand dominance, disease duration] and the presence or number of
      cortical interruptions in finger joints on high-resolution peripheral
      quantitative computed tomography (HR-pQCT). METHOD: Finger joints of 38 healthy
      subjects and 39 patients with rheumatoid arthritis (RA) were examined through
      radiographs, MRI, and HR-pQCT. Radiographs were scored according to the Sharp/van
      der Heijde (SvH) method; MRI for the presence of cortical interruptions, bone
      marrow oedema (BMO), and synovitis; and HR-pQCT images for cortical
      interruptions. Descriptive statistics were calculated and associations examined
      using generalized estimating equations. RESULTS: Cortical interruptions were
      found in healthy subjects and patients with RA on HR-pQCT (mean +/- sd 0.33 +/-
      0.63 vs 0.38 +/- 0.64 per joint quadrant, respectively, p < 0.01). Structural
      damage on MRI (cortical interruptions) or radiographs (SvH >= 1) was associated
      with the presence of cortical interruptions on HR-pQCT [odds ratio (OR) 12.4, 95%
      confidence interval (CI) 7.5-21.4, p < 0.01 and OR 4.8, 95% CI 1.9-11.7,
      respectively, p < 0.01]. The presence of BMO or synovitis was associated with
      more cortical interruptions on HR-pQCT (beta 0.47, 95% CI 0.4-0.6, p < 0.01 and
      beta 1.9, 95% CI 0.6-3.1, p < 0.01). In patients with RA, ACPA, and/or RF
      seropositivity, hand dominance and disease duration were not associated with more
      cortical interruptions on HR-pQCT. CONCLUSION: Structural damage and inflammatory
      features on MRI and radiographs are associated with cortical interruptions on HR
      pQCT. No association between other risk factors and cortical interruptions was
      demonstrated.

PMID- 29458277
TI  - Inductive Effect of a Ritonavir-Containing Hepatitis C Treatment Regimen on
      Warfarin in a Patient-A Case Report.
AB  - The warfarin management strategy for a mechanical mitral valve patient initiated
      on a ritonavir-based hepatitis C treatment regimen is described. A 62-year-old
      male with a past medical history of hepatitis C genotype 1a and stable warfarin
      dose history was initiated on a concomitant Viekira Pak(r) (VP) regimen
      containing ritonavir. Prior to initiation of the VP for hepatitis C treatment,
      the patient was stable on a warfarin dose of 40 mg/wk for 5 months. During
      treatment with VP, the patient experienced a markedly decreased international
      normalized ratio (INR) and warfarin requirements ultimately increased 125% from
      baseline (90 mg/wk). Effective anticoagulation management throughout and
      surrounding the treatment period for hepatitis C involved frequent warfarin dose
      adjustments, including preemptive changes, close monitoring, and repeated use of
      enoxaparin to ensure adequate thrombotic prophylaxis. This is believed to be the
      first reported case describing the management of warfarin in a patient with
      hepatitis C who received VP and required a drastically increased weekly warfarin
      dose. The possible mechanisms suggestive of this interaction and similar case
      reports in the literature are discussed.

PMID- 29458276
TI  - High doses of minocycline may induce delayed activation of microglia in aged rats
      and thus cannot prevent postoperative cognitive dysfunction.
AB  - Objective Postoperative cognitive dysfunction (POCD) is common after surgery in
      elderly patients and is associated with high morbidity. The molecular mechanisms
      responsible for POCD are unknown. Minocycline, an inhibitor of microglial
      activation, may be useful in treating and preventing POCD. We explored whether
      minocycline can inhibit microglial activation and prevent POCD in aged rats as a
      surgery model. Methods Rats aged 18 to 20 months were randomly allocated to the
      following groups: naive, abdominal surgery alone, or minocycline injection before
      abdominal surgery. Hippocampal cytokine mRNA levels were measured at 3 hours, 1
      day, 3 days, and 7 days after surgery, and microglial activation was measured at
      3 hours and 7 days after surgery. Memory was assessed using the Morris water maze
      test. Results Surgery resulted in severe cognitive impairment in aged rats and
      induced a significant neuroinflammatory response and microglial activation. The
      use of minocycline can prevent microglial activation after surgery, but delayed
      microglial activation may occur. The use of minocycline may further impair memory
      after surgery. Conclusion Minocycline can restrain microglial activation and
      restrict the inflammatory response in the hippocampus early after surgery, but it
      may induce delayed microglial activation and cannot prevent POCD in aged rats.

PMID- 29458279
TI  - Persistence of Mania After Cessation of Stimulation Following Subthalamic Deep
      Brain Stimulation.

PMID- 29458278
TI  - Secukinumab after anti-tumour necrosis factor-alpha therapy: a phase III study in
      active rheumatoid arthritis.
AB  - OBJECTIVE: To assess the efficacy and safety of secukinumab in patients with
      rheumatoid arthritis (RA) who failed to respond to tumour necrosis factor- alpha
      (TNF-alpha) inhibitors. METHOD: This phase III double-blind, double-dummy,
      placebo-controlled study (NCT01770379) randomized (1:1:1) patients to
      subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks
      1, 2, 3, and 4, and then every 4 weeks. American College of Rheumatology (ACR) 20
      response at week 24 was the primary endpoint. Secondary outcomes included the 28
      joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health
      Assessment Questionnaire Disability Index (HAQ-DI), and ACR50 at week 24. Long
      term treatment was planned for 5 years. RESULTS: ACR20 response rates at week 24
      for the secukinumab 150 mg and 75 mg groups were not statistically superior to
      placebo. None of the secondary endpoints was met for either secukinumab dose.
      Although not statistically significant, compared with placebo, numerically
      greater differences in least squares mean changes from baseline in HAQ-DI score
      and numerically higher ACR50 response rates were observed at week 24 in both
      secukinumab treatment groups. No new or unexpected adverse events were observed
      in this study compared with the large secukinumab safety database across
      psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies.
      CONCLUSIONS: Given that other second-line therapies have demonstrated efficacy in
      RA patients who failed to respond to TNF-alpha inhibitors, these findings may
      suggest that interleukin-17A inhibition with secukinumab does not provide
      additional benefit to these patients. This study further confirms the well
      characterized safety profile of secukinumab.

PMID- 29458280
TI  - Depressive Symptoms Are Associated With Color Vision but not Olfactory Function
      in Patients With Parkinson's Disease.
AB  - Depressive symptoms and sensory dysfunction, such as reduction in visual and
      olfactory function, are common in Parkinson's disease (PD). Previous studies have
      suggested that depressive symptoms are associated with visual impairments and
      potentially with hyposmia in several types of mood disorders. However, the
      relationship between depressive symptoms and sensory dysfunction remains unclear
      in PD. To examine the association of depressive symptoms with color vision and
      olfactory function in PD, the authors conducted a cross-sectional study in 159
      patients with PD. Depressive symptoms were measured with the Beck Depression
      Inventory-II (BDI-II) and the 30-item Geriatric Depression Scale (GDS-30); color
      vision was tested with the Farnsworth-Munsell 100 Hue Test (FMT); and olfactory
      function was tested with the Sniffin' Sticks Screening 12 Test. Results showed
      that the total error score (TES) for the FMT was significantly and independently
      correlated with scores on both the BDI-II and GDS-30 in a positive manner,
      suggesting that more severe depressive symptoms are associated with poorer color
      vision in PD. In addition, both somatic and effective subscores for the BDI-II
      were correlated with the TES on the FMT, while no significant correlation was
      observed between total scores on the Sniffin' Sticks Screening 12 Test and BDI-II
      or GDS-30. The decrease in color vision but not olfactory function was found to
      be associated with the severity of depressive symptoms in PD patients, supporting
      the idea that the occurrence of depressive symptoms in PD is linked with
      disruption of the visual system.

PMID- 29458281
TI  - Construction of a Potential Telephone Assessment of Dementia Prevalence and
      Severity.
AB  - The "delta" (for "dementia") is a latent dementia phenotype that can be
      constructed by a unique confirmatory bifactor model in a structural equation
      model framework. Because it is derived from Spearman's general intelligence
      factor, "g," delta can be constructed from any cognitive battery. This may allow
      for accurate dementia case-finding by telephone and in the absence of expert
      clinical evaluation or review. The authors constructed a new delta homolog in a
      large ethnically diverse convenience sample: the Texas Alzheimer's Research and
      Care Consortium, comprising 2,016 participants (Alzheimer's disease [AD], N=920;
      mild cognitive impairment, N=277; normal controls, N=819). A delta composite
      ("dTEL") was extracted from informant-rated Instrumental Activities of Daily
      Living and a brief battery of verbal cognitive measures. The entire battery was
      engineered to be administered over the telephone. dTEL's model had excellent fit.
      dTEL correlated strongly with dementia severity, as measured by the Clinical
      Dementia Rating "sum of boxes" scale (r=0.78, p<0.001). The dTEL composite's area
      under the receiver operating characteristic curve for the discrimination between
      control subjects and AD patients was 0.97 (95% CI=0.964-0.975). This was superior
      to all dTEL indicators. Therefore, the authors have demonstrated that a delta
      homolog composite constructed entirely from verbal measures is strongly
      associated with dementia severity, can accurately diagnose dementia, and
      outperforms all observed measures from which it is constructed. Future studies
      are required to assess dTEL's performance relative to evaluation by expert
      clinicians when obtained by lay psychometricians over the telephone.

PMID- 29458282
TI  - Cost-effectiveness of hydrophilic-coated intermittent catheters compared with
      uncoated catheters in Canada: a public payer perspective.
AB  - STUDY DESIGN: A Markov model was used to analyze cost-effectiveness over a
      lifetime horizon. OBJECTIVE: To investigate the cost-effectiveness of hydrophilic
      coated intermittent catheters (HCICs) compared with uncoated catheters (UCs)
      among individuals with neurogenic bladder dysfunction (NB) due to spinal cord
      injury (SCI). SETTING: A Canadian public payer perspective based on data from
      Ontario; including a scenario analysis from the societal perspective. METHODS: A
      previously published Markov decision model was modified to compare the lifetime
      costs and quality-adjusted life years (QALYs) for the two interventions. Three
      renal function and three urinary tract infection (UTI) health states as well as
      other catheter-related events were included. Scenario analyses, including utility
      gain from compact catheter and phthalate free catheter use, were performed.
      Deterministic and probabilistic sensitivity analyses were conducted to evaluate
      the robustness of the model. RESULTS: The model predicted that a 50-year-old
      patient with SCI would gain an additional 0.72 QALYs if HCICs were used instead
      of UCs at an incremental cost of $48,016, leading to an incremental cost
      effectiveness ratio (ICER) of $66,634/QALY. Moreover, using HCICs could reduce
      the lifetime number of UTI events by 11%. From the societal perspective, HCICs
      cost less than UCs, while providing superior outcomes in terms of QALYs, life
      years gained (LYG), and UTIs. The cost per QALY further decreased when health
      related quality-of-life (HRQoL) gains associated with compact HCICs or catheters
      not containing phthalates were included. CONCLUSION: In general, ICERs in the
      range of CAD$50-100,000 could be considered cost-effective. The ICERs for the
      base case and sensitivity analyses suggest that HCICs could be cost-effective.
      From the societal perspective, HCICs were associated with potential cost savings
      in our model. The results suggest that reimbursement of HCICs should be
      considered in these settings.

PMID- 29458283
TI  - Falling caesarean section rate and improving intra-partum outcomes: a prospective
      cohort study.
AB  - OBJECTIVE: To evaluate caesarean section (CS) rates and moderate to severe
      hypoxaemic ischaemic encephalopathy (HIE) rates with other core intra-partum
      outcomes following reconfiguration of maternity services in Cardiff, South Wales,
      UK. DESIGN: Cohort study of births from 2006 to 2015. SETTINGS: A University
      tertiary referral centre for foetal and maternal medicine with 6000 births/year,
      University Hospital of Wales, United Kingdom. METHOD: Data relating to births
      from 1 January 2006 to 31 December 2015 were extracted from the computerized
      maternity database on a yearly basis. Case notes of all mothers and babies for
      the same duration were hand searched for documentation of HIE. HIE data was also
      collected prospectively by neonatologist (SC) and obstetrician (PA). MAIN OUTCOME
      MEASURES: Incidence of caesarean section births, babies with moderate to severe
      HIE, instrumental vaginal births, obstetric anal sphincter injuries (OASIS)
      associated with instrumental delivery, and major post-partum haemorrhage (MPPH)
      of 2500 mL or more. RESULTS: During this 10-year period, a downward trend in
      emergency CS rate was seen from 15.6% in 2006 to 10.5% in 2015, reducing total CS
      rate from 25.5% in 2006 to 21.2% in 2015. A downward trend in the incidence of
      moderate and severe HIE was seen over the same period. There was an increase in
      operative vaginal births (OVB) from 12.8% to 15%. The rate of spontaneous vaginal
      births (SVB) remained stable. The incidence of OASIS remained constant and MPPH
      rate has fallen. CONCLUSIONS: Following amalgamation of two medium sized
      obstetric units and the opening of a Midwifery Led Unit (MLU), core intrapartum
      outcomes have improved. Contributing factors are the introduction of regular
      multidisciplinary training with enhanced team working, compulsory education for
      obstetricians and midwives on cardiotocograph (CTG) interpretation, increased
      consultant presence on delivery suite, robust risk management systems and broad
      multidisciplinary agreement on clinical guidelines promoting vaginal birth.

PMID- 29458284
TI  - Technical analysis of US imaging for precise microwave ablation for benign breast
      tumours.
AB  - PURPOSE: To determine the characteristics of ultrasound (US) imaging of
      completely ablated cases and the effects of duration and clinical experience on
      accurate microwave ablation (MWA) for the treatment of benign breast tumours.
      METHODS: With written informed consent and approval of the institutional ethics
      committee, patients with symptomatic or palpable benign breast tumours (longest
      diameter, 7-32 mm), to whom MWA (2450 MHz) was performed, were enrolled in this
      prospective nonrandomised study. US and contrast-enhanced US (CEUS) images were
      applied for follow-up and analysed. RESULTS: Forty-seven consecutive patients
      with 52 completely ablated tumours were enrolled. Of these 52 tumour ablations in
      US, 16 ablations were defined as concentric type, and 36 were defined as
      nonconcentric type. Of these 52 ablations, 7 cases were defined as nonaccurate
      ablation with the largest margin >=10 mm in US. The nonaccurate ablation rate in
      the training group (the first consecutive 30 cases, 7/30) was significant higher
      than that (the last 22 cases, 0/22) in the practiced group (p = 0.016). Of 38
      completely ablated cases (9 mm < the longest diameter <20 mm), the average
      largest margin in >70 s group was significant larger than that in <70 s group (p
      = 0.019). CONCLUSIONS: Experience was important for accurate MWA in the treatment
      of benign breast tumour, and at least 30 cases training was recommended.
      Nevertheless, clinical trials are still required to validate our findings in the
      future.

PMID- 29458285
TI  - Induction of autophagy by depolarization of mitochondria.
AB  - Mitochondrial dysfunction plays a crucial role in the macroautophagy/autophagy
      cascade. In a recently published study Sun et al. described the induction of
      autophagy by the membranophilic triphenylphosphonium (TPP)-based cation 10-(6'
      ubiquinonyl) decyltriphenylphosphonium (MitoQ) in HepG2 cells (Sun C, et al.
      "MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential
      [PMMP]", Autophagy 2017, 13:730-738.). Sun et al. suggested that MitoQ adsorbed
      to the inner mitochondrial membrane with its cationic moiety remaining in the
      intermembrane space, adding a large number of positive charges and establishing a
      "pseudo-mitochondrial membrane potential," which blocked the ATP synthase. Here
      we argue that the suggested mechanism for generation of the "pseudo-mitochondrial
      membrane potential" is physically implausible and contradicts earlier findings on
      the electrophoretic displacements of membranophilic cations within and through
      phospholipid membranes. We provide evidence that TPP-cations dissipated the
      mitochondrial membrane potential in HepG2 cells and that the induction of
      autophagy in carcinoma cells by TPP-cations correlated with the uncoupling of
      oxidative phosphorylation. The mild uncoupling of oxidative phosphorylation by
      various mitochondria-targeted penetrating cations may contribute to their
      reported therapeutic effects via inducing both autophagy and mitochondria
      selective mitophagy.

PMID- 29458286
TI  - Cost-effectiveness of ceritinib in previously untreated anaplastic lymphoma
      kinase-positive metastatic non-small cell lung cancer in the United States.
AB  - AIMS: To assess the cost-effectiveness of first-line ceritinib vs crizotinib and
      platinum doublet chemotherapy for anaplastic lymphoma kinase (ALK)-positive
      metastatic non-small cell lung cancer (NSCLC) from a US third-party payer's
      perspective. MATERIALS AND METHODS: A partitioned survival model with three
      health states (stable disease, progressive disease, death) was developed over a
      20-year time horizon. Ceritinib's efficacy inputs (progression-free and overall
      survival) were estimated from ASCEND-4; parametric survival models extrapolated
      data beyond the trial period. The relative efficacy of ceritinib vs chemotherapy
      was obtained from ASCEND-4, the relative efficacy of ceritinib vs crizotinib was
      estimated using a matching-adjusted indirect comparison based on ASCEND-4 and
      PROFILE 1014. Drug acquisition, treatment administration, adverse event
      management, and medical costs were obtained from publicly available databases and
      the literature, and inflated to 2016 US dollars. Treatment-specific stable-state
      utilities were derived from trials and progressive-state utility from the
      literature. Incremental costs per quality-adjusted life year (QALY) were
      estimated for ceritinib vs each comparator. Cost-effectiveness was assessed based
      on US willingness-to-pay thresholds. Deterministic and probabilistic sensitivity
      analyses were performed to test model robustness. RESULTS: In the base case,
      first-line ceritinib was associated with total direct costs of $299,777 and 3.28
      QALYs (from 4.61 life years gained [LYG]) over 20 years. First-line crizotinib
      and chemotherapy were associated with 2.73 and 2.41 QALYs, 3.92 and 3.53 LYG, and
      $263,172 and $228,184 total direct costs, respectively. The incremental cost per
      QALY gained was $66,064 for ceritinib vs crizotinib and $81,645 for ceritinib vs
      chemotherapy. In the first 2 years following treatment initiation, ceritinib
      dominated crizotinib by conferring greater health benefits at reduced total
      costs. Results were robust to deterministic and probabilistic sensitivity
      analyses. LIMITATIONS: In the absence of head-to-head trials, an indirect
      comparison method was used. CONCLUSIONS: Ceritinib is cost-effective compared to
      crizotinib and chemotherapy in the treatment of previously untreated ALK-positive
      metastatic NCSLC in the US.

PMID- 29458287
TI  - The economic impact of switching from Synthroid for the treatment of
      hypothyroidism.
AB  - AIMS: To compare hypothyroidism-related costs for patients who continuously used
      Synthroid and patients who switched from Synthroid to alternative therapies.
      MATERIALS AND METHODS: Truven's Health Analytics MarketScan Commercial Claims and
      Encounters database from January 1, 2007 to June 30, 2014 was queried for US
      adults diagnosed with hypothyroidism who initiated Synthroid and adhered to such
      therapy for at least 6 months. Propensity score matching matched continuous users
      of Synthroid to patients who switched from Synthroid to alternative levothyroxine
      agents. Kruskal-Wallis tests assessed differences between the matched cohorts in
      several categories of costs, including disease-related drug costs, non-drug
      medical costs, and total direct medical costs. RESULTS: There were 10,159
      individuals included in the study, with 7,991 continuous users of Synthroid and
      2,168 switchers. After matching (n = 2,052 for each cohort), continuous use of
      Synthroid was associated with significantly lower hypothyroidism-related non-drug
      medical costs ($595 vs $1,023; p = .003) and reduced hypothyroidism-related total
      medical costs ($757 vs $1,132; p = .010), despite being associated with
      significantly higher drug costs ($161 vs $109; p < .001). Hypothyroidism-related
      total medical costs rose as the number of switches of hypothyroidism treatment
      increased, with continuous users having significantly lower hypothyroidism
      related total medical costs ($757) compared with patients who switched twice
      ($1,179; p = .001) or three or more times ($1,268; p = .004). LIMITATIONS: The
      analyses focused on continuously insured patients who were adherent to Synthroid
      for at least 6 months and results may not be generalizable. The reliance on
      claims data does not allow for clinical examination of hypothyroidism or
      inclusion of some factors that may be associated with outcomes. The analyses
      assume that all prescriptions filled are taken as prescribed. CONCLUSIONS:
      Results indicate that there are significant direct economic healthcare costs
      associated with switching from Synthroid to alternative levothyroxine therapies,
      and that these costs increase as patients switch therapies more frequently.

PMID- 29458289
TI  - [Development of a program theory as a basis for the evaluation of a dementia
      special care unit].
AB  - Background: An existing dementia special care unit should be evaluated. In order
      to build a sound foundation of the evaluation a deep theoretical understanding of
      the implemented intervention is needed, which has not been explicated yet. One
      possibility to achieve this is the development of a program theory. Aim: The aim
      is to present a method to develop a program theory for the existing living and
      care concept of the dementia special care unit, which is used in a larger project
      to evaluate the concept theory-drivenly. Method: The evaluation is embedded in
      the framework of van Belle et al. (2010) and an action model and a change model
      (Chen, 2015) is created. For the specification of the change model the
      contribution analysis (Mayne, 2011) is applied. Data were collected in workshops
      with the developers and the nurses of the dementia special care unit and a
      literature research concerning interventions and outcomes was carried out. The
      results were synthesized in a consens workshop. Results: The action model
      describes the interventions of the dementia special care unit, the implementers,
      the organization and the context. The change model compromises the mechanisms
      through which interventions achieve outcomes. Conclusions: The results of the
      program theory can be employed to choose data collection methods and instruments
      for the evaluation. On the basis of the results of the evaluation the program
      theory can be refined and adapted.

PMID- 29458288
TI  - Delipidation of mammalian Atg8-family proteins by each of the four ATG4
      proteases.
AB  - During macroautophagy/autophagy, mammalian Atg8-family proteins undergo 2
      proteolytic processing events. The first exposes a COOH-terminal glycine used in
      the conjugation of these proteins to lipids on the phagophore, the precursor to
      the autophagosome, whereas the second releases the lipid. The ATG4 family of
      proteases drives both cleavages, but how ATG4 proteins distinguish between
      soluble and lipid-anchored Atg8 proteins is not well understood. In a fully
      reconstituted delipidation assay, we establish that the physical anchoring of
      mammalian Atg8-family proteins in the membrane dramatically shifts the way ATG4
      proteases recognize these substrates. Thus, while ATG4B is orders of magnitude
      faster at processing a soluble unprimed protein, all 4 ATG4 proteases can be
      activated to similar enzymatic activities on lipid-attached substrates. The
      recognition of lipidated but not soluble substrates is sensitive to a COOH
      terminal LIR motif both in vitro and in cells. We suggest a model whereby ATG4B
      drives very fast priming of mammalian Atg8 proteins, whereas delipidation is
      inherently slow and regulated by all ATG4 homologs.

PMID- 29458290
TI  - Neuregulin-1 accelerates corneal epithelial wound healing.
AB  - Corneal epithelial cells (CECs) play an important role in the function of the
      cornea, and are maintained by corneal epithelial stem cells (CESCs). Recent
      studies have shown that neuronal growth factors affect the proliferation and
      migration of CESCs. Neuregulin-1 (NR-1) is a neuronal growth factor that is
      expressed in the early stages of brain development. The aim of this study was to
      determine whether NR-1 activates corneal wound healing. We observed that NR-1
      activated both proliferation and migration of CECs. In addition, the colony
      forming efficacy of CESCs was enhanced. In mice, NR-1 treatment improved corneal
      wound healing. Furthermore, the expression of markers of corneal epithelium
      maintenance (DeltaNp63) and CESC proliferation (Bmi-1 and Abcg2) was increased.
      These effects were mediated by intracellular signalling pathways (Stat3, Erk1/2
      and p38). Taken together, our results suggest that NR-1 accelerates the recovery
      of corneal wounds, and may represent a novel treatment for corneal damage.

PMID- 29458291
TI  - Local Antibiotic Delivery Systems: Current and Future Applications for Diabetic
      Foot Infections.
AB  - Foot infections are common among diabetic patients with peripheral neuropathy
      and/or peripheral arterial disease, and it can be the pivotal event leading to a
      minor or major amputation of the lower extremity. Treatment of diabetic foot
      infections, especially deep-seated ones, remains challenging, in part because
      impaired blood perfusion and the presence of biofilms can impair the
      effectiveness of systemic antibiotics. The local application of antibiotics is an
      emerging field in the treatment of diabetic foot infections, with demonstrable
      advantages. These include delivery of high concentrations of antibiotics in the
      affected area, limited systemic absorption, and thus negligible side effects.
      Biodegradable vehicles, such as calcium sulfate beads, are the prototypical
      system, providing a good elution profile and the ability to be impregnated with a
      variety of antibiotics. These have largely superseded the nonbiodegradable
      vehicles, but the strongest evidence available is for calcium bead implantation
      for osteomyelitis management. Natural polymers, such as collagen sponge, are an
      emerging class of delivery systems, although thus far, data on diabetic foot
      infections are limited. There is recent interest in the novel antimicrobial
      peptide pexiganan in the form of cream, which is active against most of the
      microorganisms isolated in diabetic foot infections. These are promising
      developments, but randomized trials are required to ascertain the efficacy of
      these systems and to define the indications for their use. Currently, the role of
      topical antibiotic agents in treating diabetic foot infections is limited and
      outside of routine practice.

PMID- 29458292
TI  - Role of Coping Responses in the Relationship Between Perceived Stress and
      Psychological Well-Being in a Sample of Spanish Educational Teacher Students.
AB  - Stress in teacher education students is a key issue, due to its physical and
      social impact and its relevance to students' future as professionals. This study
      uses the Perceived Stress Scale, the Coping Responses Inventory-Adult Form, and
      the Psychological Well-Being Scale to analyze how coping strategies mediate the
      relationship between stress and well-being in a sample of Spanish teacher
      education students (n = 334). The results show that the students had a good
      general level of psychological well-being, although with little personal growth
      and autonomy. Their level of stress meant that they could offer active, engaged
      responses, although the coping strategies that were used tended to be avoidance
      type, which could lead to certain adaptive difficulties. Our results also
      indicate that coping has a partial mediating role. Finally, organizational
      actions are proposed for universities that could help to enhance students'
      personal resources for dealing with stress.

PMID- 29458293
TI  - Endoscopic mucosal resection of non-ampullary sporadic duodenal adenomas: a
      retrospective analysis with long-term follow-up.
AB  - OBJECTIVE: We investigate the efficiency of endoscopic mucosal resection (EMR) of
      non-ampullary sporadic duodenal adenomas (NASDA) in a retrospective analysis with
      long-term follow-up. METHODS: Consecutive patients undergoing EMR of NASDA
      between May 2002 and December 2016 were retrospectively identified from an
      electronic database. Endoscopic follow-up was scheduled after 3, 6 and 12 months
      for the first year, then yearly for up to five years. RESULTS: EMR of 75 NASDA
      was performed in 68 patients (56% en-bloc, 44% piecemeal). Retroperitoneal
      perforations occurred in 3/68 (4.4%) patients, were treated by surgical (n = 2)
      or percutaneous (n = 1) drainage; delayed bleeding was reported in 13/75 (17.3%)
      resections and was successfully managed by endoscopy (n = 12) or radiologic
      embolization (n = 1). There was no procedure-related mortality. Follow-up was
      available in 61/68 patients (89.7%) after a median time of 59 months from
      resection. Residual and recurrent adenoma were diagnosed in 9 (14.5%) and 6
      (10.9%) cases, respectively; all but one were successfully retreated
      endoscopically. CONCLUSIONS: EMR for NASDA is effective with a favorable long
      term outcome. Local recurrences can be retreated endoscopically. A recall system,
      patient's compliance to endoscopic follow-up are mandatory to detect recurrences
      and their prompt treatment.

PMID- 29458294
TI  - The Impact of Implementing an Intensivist Model With Nighttime In-Hospital
      Nocturnist and Effect on ICU Outcomes.
AB  - BACKGROUND: Various intensivist staffing models have been suggested, but the long
      term sustainability and outcomes vary and may not be sustained. We examined the
      impact of implementing a high-intensity intensivist coverage model with a
      nighttime in-house nocturnist (non-intensivist) and its effect on intensive care
      unit (ICU) outcomes. METHODS: We obtained historical control baseline data from
      2007 to 2011 and compared the same data from 2011 to 2015. The Acute
      Physiological and Chronic Health Evaluation outcomes system was utilized to
      collect clinical, physiological, and outcome data on all adult patients in the
      medical ICU and to provide severity-adjusted outcome predictions. The model
      consists of a mandatory in-house daytime intensivist service that leads
      multidisciplinary rounds, and an in-house nighttime coverage is provided by
      nocturnist (nonintensivists) with current procedural skills in airways
      management, vascular access, and commitment to supervise house staff as needed.
      The intensivist continues to be available remotely at nighttime for house staff
      and consultation with the nocturnist. A backup intensivist is available for surge
      management. RESULTS: First year yielded improved throughput (2428 patients/year
      to 2627 then 2724 at fifth year). Case mix stable at 53.7 versus 55.2. The ICU
      length of stay decreased from 4.7 days (predicted 4.25 days) to 3.8 days (4.15)
      in first year; second year: 3.63 days (4.29 days); third year: 3.24 days (4.37),
      fourth year: 3.34 days (4.45), and fifth year: 3.61 days (4.42). Intensive care
      unit <24 hours readmission remained at 1%; >24 hours increased from 4% to 6%. Low
      risk monitoring admissions remained at an average 17% (benchmark 17.18%).
      Intensive care unit mortality improved with standardized mortality ration
      averaging at 0.84. Resident satisfaction surveys improved. CONCLUSIONS:
      Implementing an intensivist service with nighttime nocturnist staffing in a high
      intensity large teaching hospital is feasible and improved ICU outcomes in a
      sustained manner that persisted after the initial implementation phase. The model
      resulted in reduced and sustained observed-to-predicted length of ICU stay.

PMID- 29458295
TI  - Loneliness in Men 60 Years and Over: The Association With Purpose in Life.
AB  - Loneliness as a consequence of getting older negatively impacts on the health and
      well-being of men as they age. Having a purpose in life may mitigate loneliness
      and therefore positively impact on health and well-being. Limited research into
      loneliness and purpose in life has been undertaken in older men. This study seeks
      to understand the relationship between loneliness and purpose in life in a group
      of older men. Using data from a cross-sectional survey of 614 men aged 60 years
      and over living in New Zealand, bivariate and multivariate analyses were
      undertaken to examine the relationship between loneliness and purpose in life
      using a range of demographic, health, and social connection variables. Bivariate
      analysis revealed that being unpartnered and having low socioeconomic status,
      limited social networks, low levels of participation, and mental health issues
      were associated with loneliness. Multivariate analysis showed that having poor
      mental health and lower purpose in life were indicators of loneliness.
      Consequently, improving mental health and purpose in life are likely to reduce
      loneliness in at-risk older men. As older men are a heterogeneous group from a
      variety of sociocultural and ethnic backgrounds, a multidimensional approach to
      any intervention initiatives needs to occur.

PMID- 29458296
TI  - A non-hydrocephalic goat experimental model to evaluate a ventriculosinus shunt.
AB  - The ventriculosinus shunt is a promising treatment for hydrocephalus. Currently,
      different shunt techniques exist, and it is not clear whether one is preferable.
      This pilot study reports on a non-hydrocephalic goat model (Saanen breed) that
      provides opportunities to evaluate and optimize several aspects of the
      ventriculosinus shunt technique. Analysis of the coagulation properties of 14
      goats by a viscoelastic coagulation monitor showed that goats have a
      hypercoagulable state compared to humans. This property can be partially
      counteracted by antiplatelet drugs. During implantation of a ventriculosinus
      shunt, a pulsatile reflux of blood was observed. After implantation, the animals
      recovered to their preoperative state, and none of them developed a superior
      sagittal sinus thrombosis. Evaluation of the shunts after 16 days showed an
      obstructing luminal clot. Several model-related factors may have promoted this
      obstruction: the absence of hydrocephalus, the hypercoagulability of caprine
      blood and the smaller dimensions of the caprine superior sagittal sinus. However,
      the pulsatile reflux of blood, which is caused by the compliance of the shunt
      system distal to the valve, may have been an important factor as well. In
      conclusion, the non-hydrocephalic goat model limits animal suffering and
      simplifies the study protocol. This model allows researchers to evaluate their
      implantation technique and shunt hardware but not the efficacy of the treatment
      or shunt survival.

PMID- 29458297
TI  - (R)-fluoxetine enhances cognitive flexibility and hippocampal cell proliferation
      in mice.
AB  - Fluoxetine is a clinically successful antidepressant. It is a racemic mixture of
      (R) and (S) stereoisomers. In preclinical studies, chronic treatment with
      fluoxetine (10 mg/kg) had antidepressant effects correlated with increased
      hippocampal cell proliferation in adult rodents. However, the contribution of the
      enantiomers of fluoxetine is largely unknown. We investigated the effects of
      treatment with (R)- and (S)-fluoxetine on cognitive behavioral paradigms and
      examined cell proliferation in the hippocampus of C57BL/6J female mice. In a
      behavioral sequencing task using the IntelliCage system in which discriminated
      spatial patterns of rewarded and never-rewarded corners were reversed serially,
      (R)-fluoxetine-treated mice showed rapid acquisition of behavioral sequencing
      (compared with S-fluoxetine) and cognitive flexibility in subsequent reversal
      stages in intra- and inter-session analysis. (R)-fluoxetine also increased cell
      proliferation in the hippocampus, in particular in the suprapyramidal blade of
      the dentate gyrus. (R)-fluoxetine had superior effects to (S)-fluoxetine in
      elevated plus maze, forced-swim and tail-suspension tests. These results suggest
      that (R)-fluoxetine, which has been reported to have a shorter half-life than (S)
      fluoxetine, has superior antidepressant effects and more consistently improves
      spatial learning and memory. This profile offers advantages in depression
      treatment and may also aid management of the neurocognitive impairments
      associated with depression.

PMID- 29458299
TI  - The feasibility and effectiveness of using prism adaptation to treat motor and
      spatial dysfunction in stroke survivors with multiple incidents of stroke.
AB  - Background Strokes resulting in cognitive and motor problems can be debilitating
      and prolong recovery. Risk of a second stroke occurs for 40% of all first-time
      stroke survivors within five years. Prism adaptation treatment (PAT) may
      simultaneously improve functions of both spatial and motor systems. This has not
      been studied with a cohort comprised of multiple strokes nor measured change
      using specific motor outcomes. Objectives To determine the feasibility and
      effectiveness of using PAT to improve spatial and motor functions in stroke
      survivors with multiple strokes. Method A prospective intervention with
      retrospective comparison. Thirteen participants from an inpatient rehabilitation
      facility (IRF) comprised the treatment group; 13 others who only received
      standard care comprised the comparison group. Treatment group tested on: 4 motor
      and 3 spatial outcome measures before and after the 10 PAT sessions. The
      comparison group tested on: 1 motor and 3 spatial measures before and after
      standard care. Results Thirteen participants successfully completed the PAT. Both
      groups improved on measures of spatial neglect over time (p < .001), but the
      treatment group showed greater improvement on two subtests of spatial function
      (Behavior inattention test) (p = .001 & p = .002). Similarly, both groups
      improved in motor function (Functional independence measure) (p < .001), although
      the treatment group's improvement was not statistically significant against the
      comparison group (p = .853). Conclusion PAT is a feasible treatment for stroke
      survivors with multiple strokes. PAT did improve spatial neglect function more
      than standard care, only at one level of analysis of standard paper and pencil
      measures. Further research is necessary.

PMID- 29458298
TI  - beta-amyloid inhibits hippocampal LTP through TNFR/IKK/NF-kappaB pathway.
AB  - Objective The suppressive action of the acute application of oligomeric amyloid
      beta (Abeta) on hippocampal long-term potentiation (LTP) has been reported
      widely. Many mechanisms have been proposed for Abeta inhibited LTP induction. The
      inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has also been
      reported to play a key role in this LTP inhibition through Abeta. However, the
      underlying molecular mechanisms are largely unknown. This study aimed to
      investigate the link between Abeta- and TNF-alpha-mediated hippocampal LTP
      inhibition. Methods Acute hippocampal slices of male wildtype or Alzheimer's
      disease (AD) transgenic mouse models were treated with the inhibitors of either
      TNF-alpha, IkappaB Kinase (IKK) or Nuclear Factor-kappaB (NF-kappaB) in the
      presence or absence of oligomeric Abeta42 (500 nM/2 h). The LTP was assessed
      using field excitatory post synaptic potential recordings (fEPSP), and
      immunoblotting was used to evaluate the expression of IKK and NF-kappaB. Results
      Acute treatment with Abeta or TNF-alpha alone inhibited LTP and increased the
      phosphorylation of IKK and NF-kappaB in wild type mouse hippocampal slices.
      Pretreatment with TNF-alpha antagonist infliximab rescued the LTP impairment by
      Abeta and also restored the levels of IKK and NF-kappaB to the control levels. In
      addition, pretreatment with IKK2 IV or JSH23 also restored the Abeta-mediated LTP
      impairment. Furthermore, AD transgenic mouse hippocampal slices treated with
      infliximab or inhibitors of IKK or NF-kappaB showed improved LTP and reversed the
      activation of IKK and NF-kappaB. Conclusion In conclusion, our observations
      suggest that the IKK/NF-kappaB signaling pathway play an important role in Abeta
      mediated hippocampal LTP impairment. Abeta might modulate IKK/NF-kappaB activity
      by binding or activating tumor necrosis factor receptor (TNFR).

PMID- 29458300
TI  - Ascaris lumbricoides: challenges in diagnosis, treatment and prevention
      strategies in a European refugee camp.
AB  - OBJECTIVES:  The roundworm Ascaris lumbricoides is one of the most prevalent
      parasites belonging to the class of the soil-transmitted helminths. Infections
      are most common in developing countries with a tropical climate where sanitation
      and hygiene are poor. However, prevalence of ascariasis in industrialized
      countries is increasing because of immigration and increasing number of refugees.
      METHODS:  We report a case of ascariasis in a female patient who was admitted to
      our hospital after she had left the informal refugee camp of Calais in the north
      of France. RESULTS:  After colonoscopic removal of the worm and treatment with
      mebendazole during three days the patient's symptoms had completely resolved.
      Medical treatment with benzimidazole derivatives is easy and inexpensive. To
      prevent parasitic infections in larger populations, mass drug administration
      should be repeated periodically and must be implemented along with additional
      measures such as improvements to water, sanitation and hygiene (WASH). These WASH
      programs have been proven to be highly effective, but access and follow-up are
      expensive and very difficult to organize in refugee camps, even in wealthy,
      industrialized countries. CONCLUSIONS: Despite being an old, well-known parasitic
      disease, ascariasis might reappear in certain populations at risk in
      industrialized countries. Detection, treatment and follow-up of these patients,
      and the organization of preventive measures remain challenging.

PMID- 29458301
TI  - Measurement of peripheral blood flow in patients with peripheral artery disease:
      Methods and considerations.
AB  - Peripheral artery disease (PAD) is a manifestation of generalized atherosclerosis
      which results in hemodynamic compromise of oxygen and substrate delivery to the
      lower extremity skeletal muscles. Hemodynamic assessments are vital in PAD
      diagnosis and in the evaluation of strategies aimed at treating claudication
      (i.e. exercise training, revascularization, and pharmacological agents). Venous
      occlusion plethysmography (VOP) is a century-old, non-invasive technique used to
      quantify limb blood flow and has been used to evaluate hemodynamic compromise in
      patients with PAD. However, the literature suggests a wide array of
      methodological variability in the measurement and analysis of limb blood flow
      using VOP. In this manuscript, we overview the clinical application of VOP
      measurement, and secondly we review the methodological variation that occurs
      during the measurement and analysis of VOP in healthy individuals and in patients
      with claudication.

PMID- 29458302
TI  - Spectroscopic and computational approaches to unravel the mode of binding between
      a isoflavone, biochanin-A and calf thymus DNA.
AB  - In the present study, attempt was made to explore the interaction between
      biochanin-A (BioA) and calf thymus DNA (ctDNA) by employing fluorescence
      spectroscopy, absorption spectroscopy, circular dichroism (CD), DNA melting
      studies, viscosity measurements, and molecular modeling methods. A well-known
      fluorescence probe, acridine orange (AO) was used in the present study in order
      to enhance the emission intensity of weakly fluorescent ctDNA. Quenching in
      emission intensity of ctDNA-AO system was observed in the presence of different
      concentrations of BioA, suggesting that BioA has interacted with ctDNA. The
      hyperchromic effect observed upon the addition of BioA in the absorption spectra
      of ctDNA-AO without any shift in its absorption maximum revealed that BioA was
      bound to ctDNA through groove mode of binding. Further the groove mode of binding
      of BioA to ctDNA was confirmed by DNA melting studies, viscosity measurements,
      and molecular docking studies. The results of fluorescence measurements that were
      carried out at different temperature indicated that the BioA has quenched the
      emission intensity of ctDNA-AO through static mode of quenching mechanism.
      Thermodynamic parameters revealed that the BioA-ctDNA-AO system was stabilized by
      van der Waals forces and hydrogen bonding. The effect of binding of BioA on the
      conformation of ctDNA was examined by circular dichroism studies.

PMID- 29458303
TI  - Lifestyle behaviour and risk factor control in coronary patients: Belgian results
      from the cross-sectional EUROASPIRE surveys.
AB  - OBJECTIVE: The aim of this study was to assess lifestyle behaviour as well as
      risk factor management across Belgian coronary patients who participated in the
      cross-sectional European Action on Secondary Prevention through Intervention to
      Reduce Events (EUROASPIRE) surveys. METHODS: Analyses are based on a series of
      coronary patients by combining data from the Belgian participants in the
      EUROASPIRE III (328 patients; in 2006-2007) and EUROASPIRE IV (343 patients; in
      2012-2013) surveys. Four hospitals located in the Ghent area participated in the
      surveys. Patients included in the analyses were >=18 years old and had been
      hospitalised for a coronary event. Information on cardiovascular risk factors,
      lifestyle behaviour and medical treatment were obtained. RESULTS: Overall, the
      proportion of smokers was 11% with 40% persistent smokers. Adequate physical
      activity levels were reported by 17%, 28% of patients were obese, 47% was central
      obese and known diabetes was prevalent in 21% of patients. Hypertension was
      observed in 46% of patients and 20% had a total cholesterol >=5 mmol/L. About 80%
      had participated in a cardiac rehabilitation programme and the majority of
      patients were treated with blood pressure (92%) or lipid-lowering drugs (92%).
      Anxiety and depressive symptoms were reported by 30% and 24%, respectively.
      Differences between EUROASPIRE III and IV were limited. CONCLUSIONS: Compared to
      the overall EUROASPIRE results in Europe, Belgian CHD patients seem to do
      slightly better. However, tackling obesity, physical inactivity, hypertension and
      psychosocial distress remains an important challenge in the management of
      coronary patients.

PMID- 29458304
TI  - Asbestos fiber length and its relation to disease risk.
AB  - Differences in chemical and crystalline composition, fiber dimension, aerodynamic
      characteristics and biodurability are among the critical factors that define the
      toxicological and pathological consequences of asbestos exposure. Specifically,
      fiber dimension can impact whether the fiber is respired, whether and how deeply
      it is deposited in the lung, and how efficiently and rapidly it may be cleared.
      This paper provides a current, comprehensive evaluation of the weight of evidence
      regarding the relationship between asbestos fiber length and disease potency (for
      malignant and nonmalignant endpoints). In vitro studies, animal exposure studies
      and epidemiology data were reviewed. We found that the data reported over the
      last several decades consistently support the conclusions that exposure to fibers
      longer than 10 um and perhaps 20 um are required to significantly increase the
      risk of developing asbestos-related disease in humans and that there is very
      little, if any, risk associated with exposure to fibers shorter than 5 um. Fiber
      length as a predictor of potency has been evaluated by several federal agencies
      in the U.S. and could significantly influence future regulatory decisions for
      elongated mineral particles (EMPs) and high-aspect ratio nanoparticles (HARNs).

PMID- 29458305
TI  - Estimating indoor galaxolide concentrations using predictive models based on
      objective assessments and data about dwelling characteristics.
AB  - BACKGROUND: Galaxolide (HHCB) is used for fragrance in many consumer products.
      The aim of the current study was to use objective assessments of HHCB to build a
      predictive model in order to estimate indoor-measured HHCB concentrations from
      questionnaire-based data on dwelling characteristics and occupants' habits and
      activities. METHODS: Environmental assessments of indoor HHCB, dwelling
      characteristics were carried out in 150 dwellings in Brittany (France). Among the
      various models that were tested, the best predictive model for the reduced set of
      characteristics was identified on the basis of the coefficient of determination
      (R2) criterion. RESULTS: Linear regression model showed among the best
      performances (R2 = 0.48), together with some more complex models. According to
      the estimated results, the main variables that significantly increased HHCB
      concentrations were: living in rural area, drying clothes inside dwellings,
      painted walls, chipboard furniture, double glazing, damaged floors and duration
      of bathroom door being kept open. Laminated floors and presence of indoor plants
      were found to significantly decrease HHCB concentrations. DISCUSSION: The linear
      model based on objective assessments and questionnaire-derived data about
      dwelling characteristics and occupants' activities constituted an easy method for
      predicting indoor air HHCB concentrations. For studies including a large number
      of dwellings, modeling of HHCB concentrations is cheaper than measuring it in
      every location. Our methodological procedure can be applied to other indoor air
      pollutants.

PMID- 29458306
TI  - A mechanistic review of particle overload by titanium dioxide.
AB  - Chronic exposure to titanium dioxide (TiO2) induces slight but significant
      pulmonary inflammation in experimental animals, and among potential mechanisms,
      particle overload is likely. Although mechanisms of particle overload are poorly
      understood, excess accumulation of dust particles in dust containing macrophages
      (dust cells) can impair their mobility, resulting in reduced clearance ability.
      Accordingly, retention half-times of inhaled TiO2 increase linearly with lung
      burden in rodents, and mathematical (Michaelis-Menten-like) models for pulmonary
      clearance rates of TiO2 as a function of lung burden have suggested an
      alternative mechanism for particle overload, involving excess accumulation of
      macrophages in the translocation pathway due to the narrow exit to the ciliated
      airway region, and leading to reduced pulmonary TiO2 clearance rates. This
      mechanism is consistent with observations showing that TiO2 retention half-times
      in the lungs of rats and mice show no change from the initial value until the
      lung burden exceeds around mass burden of 3 mg or surface area burden of 1000
      cm2. In addition, excess accumulation of macrophages is consistent with several
      particle overload-associated pathological changes, including accelerated
      neutrophilic inflammation, elevation of lymph node burden, and epithelial cell
      hyperplasia. Because excessive alveolar accumulation of macrophages may
      accelerate interstitialization of macrophages (including dust cells) and
      subsequent migration into lymph nodes, alveolar macrophages and dust cells likely
      migrate into interstitial spaces and escape to the luminal side of the ciliated
      airway region.

PMID- 29458307
TI  - Influence of environmental tobacco smoke on morphology and functions of
      cardiovascular system assessed using diagnostic imaging.
AB  - Exposure to tobacco smoke is a significant problem of environmental medicine.
      Tobacco smoke contains over one thousand identified chemicals including numerous
      toxicants. Cardiovascular system diseases are the major cause of general
      mortality. The recent development of diagnostic imaging provided methods which
      enable faster and more precise diagnosis of numerous diseases, also those of
      cardiovascular system. This paper reviews the most significant scientific
      research concerning relationship between environmental exposure to tobacco smoke
      and the morphology and function of cardiovascular system carried out using
      diagnostic imaging methods, i.e. ultrasonography, angiography, computed
      tomography and magnetic resonance imaging. In the forthcoming future, the studies
      using current diagnostic imaging methods should contribute to the reliable
      documentation, followed by the wide-spreading knowledge of the harmful impact of
      the environmental tobacco smoke exposure on the cardiovascular system.

PMID- 29458308
TI  - New findings about the intrascaphoid arterial system.
AB  - We investigated the intraosseous arteries of six normal cadaveric scaphoids using
      red lead injection and three-dimensional reconstruction with micro-computed
      tomography. The arterial entrances were generally located around the dorsal
      ridge, the insertion of the scaphocapitate ligament and the radial part of the
      radioscaphocapitate ligament. Two to three trunk arteries entered the scaphoid on
      dorsal ridge at the level of the waist. The distal part of the scaphoid was
      mainly supplied by arteries from the waist. The blood supply of about 40% of
      proximal part of the scaphoid was poor. The blood supply from the scaphoid dorsal
      ridge plays an important role, not only for the proximal part of the scaphoid,
      but also for the waist and even the distal pole. The intrascaphoid arterial
      pattern may be contributory to nonunion, especially in proximal pole fractures.

PMID- 29458309
TI  - A cyclic testing comparison of two flexor tendon repairs: asymmetric and modified
      Lim-Tsai techniques.
AB  - This study compared the biomechanical performance of a novel 6-strand asymmetric
      flexor tendon repair with the modified Lim-Tsai technique using cyclic testing.
      Two groups of ten porcine tendons each were repaired and tested. Gap formation at
      every 100 cycles was measured. Survival was defined as maximum gap formation
      below 2 mm. All the repairs survived Stage I. With increased cyclic load in Stage
      II, the mean gap formation of modified Lim-Tsai repairs exceeded 2 mm at the
      600th cycle and reached 4.2 mm (SD 1.93) at the end of Stage II, resulting in 0%
      survival. The mean gap formation of asymmetric repairs reached 2.0 mm (SD 1.43)
      at the 800th cycle and was 2.4 mm (SD 1.52) at the end of Stage II, with 60%
      survival. The asymmetric repair has better biomechanical performance under cyclic
      testing as compared with the modified Lim-Tsai repair.

PMID- 29458310
TI  - Flexor tendon repair in the hand with the M-Tang technique (without peripheral
      sutures), pulley division, and early active motion.
AB  - : We report outcomes in 29 patients with flexor tendon repairs in 32 digits (five
      thumbs and 27 fingers) with our modified protocols. We repaired the lacerated
      flexor digitorum profundus tendons with core suture repairs using the 6-strand M
      Tang method and without circumferential sutures. We divided the pulleys as much
      as needed to allow excursion of the repaired tendons, including complete division
      of the A4 or A2 pulleys when necessary. In nine fingers, we repaired one slip of
      the flexor digitorum superficialis tendon and resected the other half. When the
      flexor digitorum profundus tendon would not glide under the A2 pulley, we excised
      the remaining slip of the flexor digitorum superficialis tendon. The wrist was
      splinted in mild extension post-surgery with early commencement of tenodesis
      exercises. No tendon repair ruptured. By the Strickland criteria, out of 27
      fingers, 18 had excellent, six had good, two had fair, and one had poor results.
      We conclude that a strong core suture (such as the M-Tang repair) without
      peripheral sutures, and with division of pulleys as necessary is safe for early
      active motion and yields good outcomes. LEVEL OF EVIDENCE: IV.

PMID- 29458311
TI  - Double superior vena cava: presentation of two cases and review of the
      literature.
AB  - INTRODUCTION: Various anomalies in the development of the great thoracic veins of
      the embryo can be incidentally discovered in the normal adult. Duplication of
      superior vena cava (SVC) is a rare abnormality, but the most common thoracic
      venous congenital anomaly. Case reports-methods: We present two cases in the
      intensive care unit of our hospital, of asymptomatic patients who underwent an
      uneventful central line placement in the left subclavian vein. The track of the
      catheter, as shown in the X-ray, was misplaced to the left of the aorta and
      further investigation with computed tomography angiography confirmed a persistent
      left SVC. In both cases the vein drained into the coronary sinus and then to the
      right atrium. In the second case the echocardiography revealed a dilated coronary
      sinus. CONCLUSIONS: Double SVC can be fortuitously discovered during catheter
      insertion, thoracic or cardiac imaging and surgery. In most cases it drains into
      the right atrium, through the coronary sinus. This entity is significant to the
      physician because of its importance in differential diagnosis as a cause of a
      widened mediastinum, as well as any difficulty that can occur in the placement of
      a central venous catheter or a pace maker.

PMID- 29458312
TI  - Reflections on researcher departure: Closure of prison relationships in
      ethnographic research.
AB  - BACKGROUND: The United Kingdom has the highest incarceration rate in Western
      Europe. It is known that women in prison are a vulnerable female population who
      are at risk of mental ill-health due to disadvantaged and chaotic life
      experiences. Accurate numbers of pregnant women held in UK prisons are not
      recorded, yet it is estimated that 6%-7% of the female prison population are at
      varying stages of pregnancy and around 100 babies are born to incarcerated women
      each year. There are limited published papers that document the departure of the
      researcher following closure of fieldwork with women in prison. This article
      identifies the dilemmas and challenges associated with the closure of prison
      fieldwork through the interwoven reflections of the researcher. Departure
      scenarios are presented which illuminate moments of closure talk with five women,
      supported by participant reflections regarding abandonment and loss, making
      pledges for the future, self-affirmation, incidental add-ons at the end of an
      interview and red flags, alerting the researcher to potential participant harm
      through ill health or self-injury. OBJECTIVES: The primary intention of the study
      was to observe the pregnant woman's experience with the English prison system
      through interviews with pregnant women and field observations of the environment.
      RESEARCH DESIGN: Ethnographic design enabled the researcher, a practising
      midwife, to engage with the prisoners' pregnancy experiences in three English
      prisons, which took place over 10 months during 2015-2016. Data collection
      involved semi-structured, audio-recorded interviews with 28 female prisoners in
      England who were pregnant or had recently given birth while imprisoned, 10
      members of staff and a period of non-participant observation. Follow-up
      interviews with 5 women were undertaken as their pregnancies progressed.
      Computerised qualitative data analysis software was used to generate and analyse
      pregnancy-related themes. Ethical considerations: Favourable ethical opinion was
      granted by National Offender Management Services through the Health Research
      Authority Integrated Research Application System and permission to proceed was
      granted by the University of Hertfordshire, UK. FINDINGS: Thematic analysis
      enabled the identification of themes associated with the experience of prison
      pregnancy illuminating how prison life continues with little consideration for
      their unique physical needs, coping tactics adopted and the way women negotiate
      entitlements. On researcher departure from the field, the complex feelings of
      loss and sadness were experienced by both participants and researcher.
      DISCUSSION: To leave the participant with a sense of abandonment following
      closure of fieldwork, due to the very nature of the closed environment, risks re
      enactment of previous emotional pain of separation. Although not an ethical
      requirement, the researcher sought out psychotherapeutic supervision during the
      fieldwork phase with 'Janet', a forensic psychotherapist, which helped to
      highlight the need for careful closure of research/participant relationships with
      a vulnerable population. This article brings to the consciousness of prison
      researchers the need to minimise potential harm by carefully negotiating how to
      exit the field. Reflections of the researcher are interlinked with utterances
      from some participants to illustrate the types of departure behaviours.
      CONCLUSION: Closure of fieldwork and subsequent researcher departure involving
      pregnant women in prison requires careful handling to uphold the ethical research
      principle 'do no harm'.

PMID- 29458313
TI  - How to succeed with ethics reflection groups in community healthcare?
      Professionals' perceptions.
AB  - BACKGROUND: Healthcare personnel in the municipal healthcare systems experience
      many ethical challenges in their everyday work. In Norway, 243 municipalities
      participated in a national ethics project, aimed to increase ethical competence
      in municipal healthcare services. In this study, we wanted to map out what
      participants in ethics reflection groups experienced as promoters or as barriers
      to successful reflection. OBJECTIVES: To examine what the staff experience as
      promoters or as barriers to successful ethics reflection. RESEARCH DESIGN: The
      study has a qualitative design, where 56 participants in municipal healthcare
      participated in 10 different focus-group interviews. Ethical considerations: The
      data collection was based on the participants' informed consent and approved by
      the Data Protection Official of the Norwegian Centre for Research Data. RESULTS:
      The informants had different experiences from ethics reflection group.
      Nevertheless, we found that there were several factors that were consistently
      mentioned: competence, facilitator's role, ethics reflection groups organizing,
      and organizational support were all experienced as promoters and as a significant
      effect on ethics reflection groups. The absence of such factors would constitute
      important barriers to successful ethics reflection. DISCUSSION: The results are
      coincident with other studies, and indicate some conditions that may increase the
      possibility to succeed with ethics reflection groups. A systematic approach seems
      to be important, the systematics of the actual reflections, but also in the
      organization of ethics reflection group at the workplace. Community healthcare is
      characterized by organizational instabilities as many vacancies, high workloads,
      and lack of predictability. This can be a hinder for ethics reflection group.
      CONCLUSION: Both internal and external factors seem to influence the organization
      of ethics reflection group. The municipalities' instabilities challenging this
      work, and perceived as a clear inhibitor for the development. The participants
      experienced that the facilitator is the most important success factor for
      establishing, carrying out, and to succeed with ethics reflection groups.

PMID- 29458314
TI  - A blended-learning programme regarding professional ethics in physiotherapy
      students.
AB  - BACKGROUND: In the university context, assessing students' attitude, knowledge
      and opinions when applying an innovative methodological approach to teach
      professional ethics becomes fundamental to know if the used approach is enough
      motivating for students. RESEARCH OBJECTIVE: To assess the effect of a blended
      learning model, based on professional ethics and related to clinical practices,
      on physiotherapy students' attitude, knowledge and opinions towards learning
      professional ethics. Research design and participants: A simple-blind clinical
      trial was performed (NLM identifier NCT03241693) (control group, n = 64;
      experimental group, n = 65). Both groups followed clinical practices for 8
      months. Control group performed a public exposition of a clinical case about
      professional ethics. By contrast, an 8-month blended-learning programme regarding
      professional ethics was worked out for experimental group. An online syllabus and
      online activities were elaborated, while face-to-face active participation
      techniques were performed to discuss ethical issues. Students' attitudes,
      knowledge and opinions towards learning professional ethics were assessed.
      Ethical considerations: The study was approved by the University Ethic Committee
      of Human Research and followed the ethical principles according to the
      Declaration of Helsinki. FINDINGS: After the programme, attitudes and knowledge
      towards learning professional ethics of experimental group students significantly
      improved, while no differences were observed in control group. Moreover, opinions
      reported an adequate extension of themes and temporization, importance of
      clinical practices and interest of topics. Case study method and role playing
      were considered as the most helpful techniques. CONCLUSION: The blended-learning
      programme proposed, based on professional ethics and related to clinical
      practices, improves physiotherapy students' attitudes, knowledge and opinions
      towards learning professional ethics.

PMID- 29458315
TI  - The disconnect between nutrition guidelines and evidence: how much protein should
      I prescribe to this critically ill patient?

PMID- 29458316
TI  - Study protocol for the Augmented versus Routine Approach to Giving Energy Trial
      (TARGET).
AB  - BACKGROUND: Nutrition is routinely provided to critically ill patients who are
      mechanically ventilated and remain in the intensive care unit for more than a few
      days. Nasogastric feeding, which is standard practice for patients who are unable
      to tolerate oral nutrition, typically delivers less than 60% of the recommended
      energy requirements. It remains uncertain whether the delivery of about 100% of
      the recommended energy goals via the enteral route will affect survival and other
      important clinical outcomes. OBJECTIVE: To describe the protocol for a large
      scale, multicentre, double-blind, randomised, controlled, parallelgroup, phase 3
      clinical trial to determine if augmentation of calorie delivery using an energy
      dense enteral nutrition formulation in mechanically ventilated patients increases
      90-day survival when compared with routine care. METHODS: 4000 patients who are
      mechanically ventilated and are expected to receive enteral nutrition for more
      than 2 days are to be randomised to an energy-dense formulation (1.5 kcal/mL) or
      routine enteral feed formulation (1 kcal/mL), given at the same rate. The primary
      outcome is 90-day all-cause mortality. Secondary outcomes include cause-related
      mortality up to Day 90; all-cause mortality at hospital discharge and at Days 28
      and 180 after randomisation; and ventilator-, vasopressorand renal replacement
      free days to Day 28. Health-related quality of life and functional assessments
      will be conducted at Day 180 after randomisation. RESULTS AND CONCLUSIONS: The
      results of this trial are expected to determine whether increased energy
      delivery, using an energy-dense formula can improve clinically meaningful
      outcomes, including survival.

PMID- 29458317
TI  - Statistical analysis plan for the Augmented versus Routine Approach to Giving
      Energy Trial (TARGET).
AB  - BACKGROUND: The Augmented versus Routine Approach to Giving Energy Trial (TARGET)
      is a 4000-patient randomised, double-blind controlled trial designed to evaluate
      whether enteral delivery of recommended energy goals using a 1.5 kcal/mL enteral
      nutrition formulation improves clinical outcomes, compared with a 1 kcal/mL
      enteral nutrition formulation delivered at the same goal rate, in critically ill
      patients receiving invasive mechanical ventilation. OBJECTIVE: In keeping with
      best practice, and in accordance with other trials conducted by the
      investigators, a pre-specified statistical analysis plan has been described and
      made public before completion of patient recruitment and data collection into the
      TARGET trial. METHODS: Our statistical analysis plan was designed by the TARGET
      chief investigators and statisticians and approved by the TARGET Management
      Committee. We reviewed the data collected as specified in the trial protocol and
      collected in the case report form. We present information pertaining to data
      collection, pre-specified subgroups, processes of care and trial outcomes.
      Primary and secondary outcomes are defined and methods for assessing functional
      outcomes (secondary outcomes) are described. RESULTS: We have developed a
      statistical analysis plan that includes our methods for presenting the trial
      profile, baseline characteristics, processes of care, outcomes and adverse
      events. Seven pre-specified subgroups and our methods for statistical comparisons
      between groups are described. CONCLUSION: We have developed a pre-specified
      statistical analysis plan for TARGET. To minimise analytical bias, this plan has
      been developed and made available to the public domain before completing
      recruitment and data collection.

PMID- 29458318
TI  - Protocol summary and statistical analysis plan for the intensive care unit
      randomised trial comparing two approaches to oxygen therapy (ICU-ROX).
AB  - BACKGROUND: The balance of risks and benefits of conservative v standard care
      oxygen strategies for patients who are invasively ventilated in the intensive
      care unit (ICU) is uncertain. OBJECTIVE: To describe the study protocol and
      statistical analysis plan for the ICU randomised trial comparing two approaches
      to oxygen therapy (ICU-ROX). DESIGN, SETTING AND PARTICIPANTS: Protocol for a
      multicentre, randomised, participant and outcome assessor-blinded, standard care
      controlled, parallel-group, two-sided superiority trial to be conducted in up to
      22 ICUs in Australia and New Zealand. 1000 adults who are mechanically ventilated
      in the ICU and expected to remain ventilated beyond the day after recruitment
      will be randomly assigned to conservative oxygen therapy or standard care in a
      1:1 ratio. ICU-ROX began with an internal pilot phase in September 2015. It is
      anticipated that recruitment will be completed in 2018. MAIN OUTCOME MEASURES:
      The primary endpoint will be alive, ventilator-free days to Day 28. Secondary
      outcomes include 90- and 180-day all-cause mortality, survival time to 180 days,
      and quality of life and cognitive function at 180 days. All analyses will be
      conducted on an intentionto- treat basis. RESULTS AND CONCLUSIONS: ICU-ROX will
      compare the effect of conservative v standard oxygen therapy in critically ill
      mechanically ventilated adults who are expected to be ventilated beyond the day
      after recruitment on ventilatorfree days to Day 28. TRIAL REGISTRATION:
      Australian and New Zealand Clinical Trials Registry (ANZCTRN 12615000957594).

PMID- 29458319
TI  - Proportional assist ventilation versus pressure support ventilation in weaning
      ventilation: a pilot randomised controlled trial.
AB  - OBJECTIVE: Proportional assist ventilation with load-adjustable gain factors
      (PAV+) is a mode of ventilation that provides assistance in proportion to patient
      effort. This may have physiological and clinical advantages when compared with
      pressure support ventilation (PSV). Our objective was to compare these two modes
      in patients being weaned from mechanical ventilation. DESIGN: Prospective
      randomised controlled trial comparing PSV with PAV+. SETTING: University
      affiliated, tertiary referral intensive care unit (ICU). PARTICIPANTS:
      Mechanically ventilated patients on a controlled mode of ventilation for at least
      24 hours, who were anticipated to be spontaneously ventilated for at least 48
      hours after randomisation. INTERVENTIONS: Nil. MAIN OUTCOME MEASURES: The primary
      outcome was time to successful liberation from the ventilator after the
      commencement of a spontaneous mode of ventilation. Secondary outcomes were
      requirement of rescue (mandatory) ventilation, requirement of sedative drugs,
      requirement for tracheostomy, re-intubation within 48 hours of extubation, ICU
      length of stay (LOS), hospital LOS, and ICU and hospital mortality. RESULTS: 50
      patients were randomised to either PSV (n = 25) or PAV+ (n = 25). There was no
      significant difference between the PAV+ and PSV groups in time to successful
      weaning (84.3 v 135.9 hours, respectively; P = 0.536). Four patients randomised
      to PAV+ were crossed over to PSV during weaning. There was no significant
      difference between groups for rescue ventilation, reintubation within 48 hours,
      tracheostomy, sedatives and analgesics prescribed, and ICU and hospital LOS. ICU
      mortality was higher in the PSV group (25% v 4 %; P = 0.002). CONCLUSIONS: Both
      modes of ventilation were comparable in time to liberation from the ventilator.

PMID- 29458320
TI  - Evaluation of urea and creatinine change during continuous renal replacement
      therapy: effect of blood flow rate.
AB  - OBJECTIVE: To determine if faster blood flow rate (BFR) has an effect on solute
      maintenance in continuous renal replacement therapy. DESIGN: Prospective
      randomised controlled trial. SETTING: 24-bed, single centre, tertiary level
      intensive care unit. PARTICIPANTS: Critically ill adults requiring continuous
      renal replacement therapy (CRRT). INTERVENTIONS: Patients were randomised to
      receive one of two BFRs: 150 mL/min or 250 mL/min. MAIN OUTCOME MEASURES: Changes
      in urea and creatinine concentrations (percentage change from baseline) and
      delivered treatment for each 12-hour period were used to assess solute
      maintenance. RESULTS: 100 patients were randomised, with 96 completing the study
      (49 patients, 150 mL/min; 47 patients, 250 mL/min). There were a total of 854 12
      hour periods (421 periods, 150 mL/min; 433 periods, 250 mL/ min). Mean hours of
      treatment per 12 hours was 6.3 hours (standard deviation [SD], 3.7) in the 150
      mL/min group, and 6.7 hours (SD, 3.9) in the 250 mL/min group (P = 0.6). There
      was no difference between the two BFR groups for change in mean urea
      concentration (150 mL/min group, -0.06%; SD, 0.015; v 250 mL/min group, -0.07%;
      SD, 0.01; P = 0.42) or change in mean creatinine concentration (150 mL/min, 
      0.05%; SD, 0.01; v 250 mL/min, -0.08%; SD, 0.01; P = 0.18). Independent variables
      associated with a reduced percentage change in mean serum urea and creatinine
      concentrations were low haemoglobin levels (-0.01%; SD, 0.005; P = 0.002; and
      0.01%; SD, 0.005; P = 0.006, respectively) and less hours treated (-0.023%; SD,
      0.001; P = 0.000; and -0.02%; SD, 0.002; P = 0.001, respectively). No effect for
      bodyweight was found. CONCLUSIONS: Faster BFR did not affect solute control in
      patients receiving CRRT; however, differences in urea and creatinine
      concentrations were influenced by serum haemoglobin and hours of treatment.

PMID- 29458321
TI  - Differential effects of isotonic and hypotonic 4% albumin solution on
      intracranial pressure and renal perfusion and function.
AB  - OBJECTIVES: Albumin is used to resuscitate trauma patients but may increase
      intracranial pressure (ICP). Its effects on renal blood flow and function are
      unknown. Our aim was to examine the effects of hypertonic albumin on ICP and
      renal function, and if any effects are due to the hypotonicity of the solution
      containing albumin or to albumin itself. DESIGN, SETTING AND SUBJECTS: Cross
      over, randomised controlled experimental study of six adult Merino ewes in the
      animal facility of a research institute. METHOD: Sheep were implanted with flow
      probes around the pulmonary and renal arteries and an ICP monitoring catheter in
      a lateral cerebral ventricle. Conscious sheep received normal saline,
      commercially available hypotonic 4% albumin solution (4% Albumex [278 mOsm/kg])
      or a novel isotonic 4% albumin solution (288 mOsm/kg), with at least 48 hours
      between each intervention. RESULTS: Commercial hypotonic albumin solution
      increased ICP (by 8.5 mmHg [SEM, 2.1 mmHg]; P < 0.01), but neither isotonic
      albumin solution nor saline significantly changed ICP. The increase in ICP with
      hypotonic albumin solution was associated with an increase in central venous
      pressure (CVP) (by 5.4 mmHg [SEM, 0.6 mmHg]; P < 0.001), but no significant
      changes in cardiac output or stroke volume. None of the infusions changed renal
      blood flow, plasma creatinine level, creatinine clearance or plasma or urinary
      electrolyte levels. CONCLUSION: Compared with saline or isotonic albumin
      solution, hypotonic albumin solution increased ICP and CVP, but did not alter
      arterial pressure, cardiac output renal blood flow or renal function. Our
      findings support the view that the tonicity of the albumin solution, rather than
      the albumin itself, is responsible for increasing ICP.

PMID- 29458322
TI  - Predicting recovery from acute kidney injury in critically ill patients:
      development and validation of a prediction model.
AB  - OBJECTIVE: Intensive care unit (ICU) patients with acute kidney injury (AKI) who
      recover kidney function within 28 days experience less severe chronic kidney
      impairment and have increased long term survival. The aims of this study were to
      develop and validate a risk prediction model to identify these patients. DESIGN:
      Observational study with development and validation of a risk prediction model.
      SETTING: Nine academic ICUs in Denmark. PARTICIPANTS: Development cohort of
      critically ill patients with AKI at ICU admission from the Procalcitonin and
      Survival Study cohort (n = 568), validation cohort of adult patients with AKI
      admitted to two university hospitals in Denmark in 2012-13 (n = 766).
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Recovery of kidney function was
      defined as living for 5 consecutive days with no renal replacement therapy and
      with creatinine plasma levels below 1.5-fold the levels determined before ICU
      admission. RESULTS: A total of 266 patients (46.8%) recovered prior kidney
      function in the development cohort, and 453 patients (59.1%) in the validation
      cohort. The prediction model included elevation in creatinine, urinary output,
      sex and age. In the validation cohort, 69 patients (9.0%) had a predicted chance
      of recovery < 25%, and their observed rate of recovery was 21.5%. This observed
      rate of recovery was 81.7% among the 325 patients who had a predicted chance >
      75%. The area under the receiver operations curves for predicting recovery in the
      validation cohort was 73.1%. CONCLUSION: We constructed and validated a simple
      model that can predict the chance of recovery from AKI in critically ill
      patients.

PMID- 29458323
TI  - A randomised controlled trial to determine the effectiveness of a radial arterial
      catheter dressing.
AB  - OBJECTIVE: To reduce radial arterial catheter failure in patients admitted to an
      adult intensive care unit (ICU). DESIGN: A randomised controlled trial. SETTING:
      A single site, large metropolitan tertiary referral public hospital.
      PARTICIPANTS: Three hundred participants admitted to an adult ICU were enrolled
      between 25 May and 13 September 2015. INTERVENTIONS: Participants were randomly
      assigned to one of two treatment groups (a polyurethane adhesive keyhole dressing
      or a polyurethane adhesive keyhole dressing together with a polyurethane
      semipermeable transparent dressing). MAIN OUTCOME MEASURE: Arterial catheter
      failure. RESULTS: Data were complete for 289 of the 300 adult participants, who
      were randomised to one of the two groups. There were 179 men (62%) with a median
      age of 61 years (IQR, 48-74). Overall, there were 109 arterial catheter failures
      (38%). There was a significantly higher catheter failure rate in the usual care
      group (65, 60%) compared with the intervention group (44, 40%; P = 0.05).
      Accidental catheter removal occurred in 87% of cases (n = 27) in the usual care
      group and in 13% of cases (n = 4) in the intervention group (P = 0.05). There was
      no significant difference between the two groups for time to catheter failure (P
      = 0.06). However, if patients were sedated, they were 54% less likely to
      experience arterial catheter failure (OR, 0.46; 95% CI, 0.31-0.67; P < 0.0001).
      CONCLUSION: This study showed a statistically significant reduction in arterial
      catheter failure using a radial arterial catheter dressing of a polyurethane
      adhesive keyhole dressing together with a polyurethane semipermeable transparent
      dressing. The nursing care technique of applying this dressing may improve
      dressing efficacy and patient safety and reduced costs.

PMID- 29458324
TI  - Smoking cessation therapy in Australian and New Zealand intensive care units: a
      multicentre point prevalence study.
AB  - OBJECTIVE: To obtain an accurate estimate of smoking prevalence and smoking
      cessation support practices, including nicotine replacement therapy (NRT), in
      Australian and New Zealand intensive care units (ICUs). DESIGN, SETTING AND
      PARTICIPANTS: Cross-sectional, observational study using data obtained from adult
      ICUs participating in the Australian and New Zealand Intensive Care Society
      Clinical Trials Group Point Prevalence Program in 2016. MAIN OUTCOME MEASURES:
      Prevalence and intensity of current smoking, baseline characteristics of smokers
      in comparison with non-smokers and frequency of NRT use while admitted to the
      ICU. RESULTS: Smoking data were present for 551 of 671 adult ICU patients from 47
      ICUs on 2 study days in 2016. Of these 551 patients, 112 were current smokers
      (20.3%; 95% CI, 17.0-23.9%). No significant differences in severity of illness or
      mortality were observed between smokers and non-smokers. NRT was prescribed to
      30/112 smokers (26.8%), and in 28 of those 30 patients (93%) it was administered
      via nicotine patch alone. Routine prescribing of NRT was practised in 28/47 ICUs
      (60%), and 24/47 ICUs (51%) had formal protocols or guidelines in place related
      to supporting smoking cessation. CONCLUSIONS: The prevalence of smoking in
      Australian and New Zealand ICUs patients is high. Over half of participating ICUs
      reported the routine prescription of NRT despite uncertainty regarding the
      practice. Further research evaluating the safety and efficacy of NRT is required.

PMID- 29458325
TI  - Comparison of continuous-wave Doppler ultrasound monitor and echocardiography to
      assess cardiac output in intensive care patients.

PMID- 29458326
TI  - Global study of holistic morphological effectors in the budding yeast
      Saccharomyces cerevisiae.
AB  - BACKGROUND: The size of the phenotypic effect of a gene has been thoroughly
      investigated in terms of fitness and specific morphological traits in the budding
      yeast Saccharomyces cerevisiae, but little is known about gross morphological
      abnormalities. RESULTS: We identified 1126 holistic morphological effectors that
      cause severe gross morphological abnormality when deleted, and 2241 specific
      morphological effectors with weak holistic effects but distinctive effects on
      yeast morphology. Holistic effectors fell into many gene function categories and
      acted as network hubs, affecting a large number of morphological traits,
      interacting with a large number of genes, and facilitating high protein
      expression. Holistic morphological abnormality was useful for estimating the
      importance of a gene to morphology. The contribution of gene importance to
      fitness and morphology could be used to efficiently classify genes into
      functional groups. CONCLUSION: Holistic morphological abnormality can be used as
      a reproducible and reliable gene feature for high-dimensional morphological
      phenotyping. It can be used in many functional genomic applications.

PMID- 29458328
TI  - Dynamics of promoter bivalency and RNAP II pausing in mouse stem and
      differentiated cells.
AB  - BACKGROUND: Mammalian embryonic stem cells display a unique epigenetic and
      transcriptional state to facilitate pluripotency by maintaining lineage
      specification genes in a poised state. Two epigenetic and transcription processes
      involved in maintaining poised state are bivalent chromatin, characterized by the
      simultaneous presence of activating and repressive histone methylation marks, and
      RNA polymerase II (RNAPII) promoter proximal pausing. However, the dynamics of
      histone modifications and RNAPII at promoters in diverse cellular contexts
      remains underexplored. RESULTS: We collected genome wide data for bivalent
      chromatin marks H3K4me3 and H3K27me3, and RNAPII (8WG16) occupancy together with
      expression profiling in eight different cell types, including ESCs, in mouse. The
      epigenetic and transcription profiles at promoters grouped in over thirty
      clusters with distinct functional identities and transcription control.
      CONCLUSION: The clustering analysis identified distinct bivalent clusters where
      genes in one cluster retained bivalency across cell types while in the other were
      mostly cell type specific, but neither showed a high RNAPII pausing. We noted
      that RNAPII pausing is more associated with active genes than bivalent genes in a
      cell type, and was globally reduced in differentiated cell types compared to
      multipotent.

PMID- 29458327
TI  - Histone modification profiling in breast cancer cell lines highlights
      commonalities and differences among subtypes.
AB  - BACKGROUND: Epigenetic regulators are frequently mutated or aberrantly expressed
      in a variety of cancers, leading to altered transcription states that result in
      changes in cell identity, behavior, and response to therapy. RESULTS: To define
      alterations in epigenetic landscapes in breast cancers, we profiled the
      distributions of 8 key histone modifications by ChIP-Seq, as well as primary (GRO
      seq) and steady state (RNA-Seq) transcriptomes, across 13 distinct cell lines
      that represent 5 molecular subtypes of breast cancer and immortalized human
      mammary epithelial cells. DISCUSSION: Using combinatorial patterns of distinct
      histone modification signals, we defined subtype-specific chromatin signatures to
      nominate potential biomarkers. This approach identified AFAP1-AS1 as a triple
      negative breast cancer-specific gene associated with cell proliferation and
      epithelial-mesenchymal-transition. In addition, our chromatin mapping data in
      basal TNBC cell lines are consistent with gene expression patterns in TCGA that
      indicate decreased activity of the androgen receptor pathway but increased
      activity of the vitamin D biosynthesis pathway. CONCLUSIONS: Together, these
      datasets provide a comprehensive resource for histone modification profiles that
      define epigenetic landscapes and reveal key chromatin signatures in breast cancer
      cell line subtypes with potential to identify novel and actionable targets for
      treatment.

PMID- 29458329
TI  - Mouse chromocenters DNA content: sequencing and in silico analysis.
AB  - BACKGROUND: Chromocenters are defined as a punctate condensed blocks of chromatin
      in the interphase cell nuclei of certain cell types with unknown biological
      significance. In recent years a progress in revealing of chromocenters protein
      content has been made although the details of DNA content within constitutive
      heterochromatin still remain unclear. It is known that these regions are enriched
      in tandem repeats (TR) and transposable elements. Quick improvement of genome
      sequencing does not help to assemble the heterochromatic regions due to lack of
      appropriate bioinformatics techniques. RESULTS: Chromocenters DNA have been
      isolated by a biochemical approach from mouse liver cells nuclei and sequenced on
      the Illumina MiSeq resulting in ChrmC dataset. Analysis of ChrmC dataset by the
      bioinformatics tools available revealed that the major component of chromocenter
      DNA are TRs: ~ 66% MaSat and ~ 4% MiSat. Other previously classified TR families
      constitute ~ 1% of ChrmC dataset. About 6% of chromocenters DNA are mostly
      unannotated sequences. In the contigs assembled with IDBA_UD there are many
      fragments of heterochromatic Y-chromosome, rDNA and other pseudo-genes and non
      coding DNA. A protein coding sfi1 homolog gene fragment was also found in
      contigs. The Sfi1 homolog gene is located on the chromosome 11 in the reference
      genome very close to the Golden Pass Gap (a ~ 3 Mb empty region reserved to the
      pericentromeric region) and proves the purity of chromocenters isolation. The
      second major fraction are non-LTR retroposons (SINE and LINE) with overwhelming
      majority of LINE - ~ 11% of ChrmC. Most of the LINE fragments are from the ~ 2 kb
      region at the end of the 2nd ORF and its' flanking region. The precise LINEs'
      segment of ~ 2 kb is the necessary mouse constitutive heterohromatin component
      together with TR. The third most abundant fraction are ERVs. The ERV distribution
      in chromocenters differs from the whole genome: IAP (ERV2 class) is the most
      numerous in ChrmC while MaLR (ERV3 class) prevails in the reference genome. IAP
      and its LTR also prevail in TR containing contigs extracted from the WGS dataset.
      In silico prediction of IAP and LINE fragments in chromocenters was confirmed by
      direct fluorescent in situ hybridization (FISH). CONCLUSION: Our data of
      chromocenters' DNA (ChrmC) sequencing demonstrate that IAP with LTR and a precise
      ~ 2 kb fragment of LINE represent a substantial fraction of mouse chromocenters
      (constitutive heteroshromatin) along with TRs.

PMID- 29458330
TI  - Gait pattern in patients with peripheral artery disease.
AB  - BACKGROUND: The aim of the present paper is to assess the gait pattern of
      patients with Peripheral Artery Disease (PAD). A more specific aim is to compare
      the gait pattern of PAD patients before and after the appearance of intermittent
      claudication symptoms. METHODS: The study involved 34 PAD patients with a
      claudication distance >=200 m and 20 participants without PAD, who formed the
      control group. The gait pattern of PAD patients was assessed twice: before the
      appearance of intermittent claudication symptoms (pain-free conditions) and after
      the appearance of intermittent claudication symptoms (pain conditions). RESULTS:
      Compared to the control group, PAD patients presented a statistically significant
      decrease in step length both during pain-free conditions (52.6 +/- 12.5 vs. 72.8
      +/- 18.5 cm, p = 0.008) and in pain conditions (53.3 +/- 13.3 vs. 72.8 +/- 18.5
      cm, p = 0.006). As for the remaining spatiotemporal parameters, there were no
      differences observed between the patient group and the controls. Intermittent
      claudication symptom induced by the walking test on the treadmill did not bring
      about any new abnormalities in the gait pattern or intensify the existing
      abnormalities of the gait. CONCLUSIONS: PAD patients have a tendency to shorten
      their step length regardless of the presence of intermittent claudication.

PMID- 29458331
TI  - Correction to: Identification of tRNA nucleoside modification genes critical for
      stress response and development in rice and Arabidopsis.
AB  - CORRECTION: Following publication of the original article [1], the authors
      reported that there was a mistake in the presentation of their funding
      information. The sentence "This study was supported by the National Natural
      Science Foundation of China (31,100,268 to Peng Chen, 31,270,658 to Bo Zheng);"
      should instead read "This study was supported by the National Natural Science
      Foundation of China (31100268 to Peng Chen, 31370604 to Bo Zheng);".

PMID- 29458333
TI  - Pre-anesthetic assessment with three core questions for the detection of
      obstructive sleep apnea in childhood: An observational study.
AB  - BACKGROUND: Children with obstructive sleep apnea are at high risk for
      perioperative airway obstruction. Many "at risk" children may remain
      unrecognized. The aim of this study is to find a clinically practicable test to
      identify obstructive sleep apnea in childhood. METHODS: In this pilot study, we
      prospectively compared four parental questionnaires with the respective findings
      of subsequent sleep laboratory testing in children. Right before sleep laboratory
      testing, children's parents answered both the Pediatric Sleep Questionnaire, a
      subscale of the Sleep Related Breathing Disorder questionnaire (PSQ-SRBD
      Subscale), and an eight-item questionnaire derived from it. Finally, we condensed
      the eight-item questionnaire to three core issues: Does your child regularly
      snore at night? Does your child demonstrate labored breathing during sleep? Does
      your child have breathing pauses during sleep? With it, two similar
      questionnaires were generated that differed in the formation of the resulting
      score. One questionnaire was built by a quotient comparable to the abovementioned
      questionnaires and a second as quick test that functioned as a simple sum score.
      Both sensitivity and specificity were determined by using a Receiver Operating
      Characteristic analysis. RESULTS: In total, 53 children were included in the
      study. Both the PSQ-SRBD-questionnaire and self-derived eight-item questionnaire
      failed to reach statistically significant results in detecting obstructive sleep
      apnea. The set of three core questions with a score built by a quotient was
      statistically significant and provided sensitivity and a moderate specificity of
      0.944 and 0.543, respectively. This could be slightly optimized by creating a
      simple sum-score (specificity of 0.571). CONCLUSIONS: The use of three core
      questions may facilitate the detection of pediatric obstructive sleep apnea
      within the scope of the anesthesia survey. While the study has some limitations,
      future studies with both unselective collectives and older children might prove
      this ultra-short questionnaire to be advantageous in detecting pediatric OSA in
      clinical practices. TRIAL REGISTRATION: German Clinical Trial Register (
      DRKS00010408 , https://www.drks.de ); date of registration 26.07.2016.

PMID- 29458332
TI  - Identification of genetic variants for clinical management of familial colorectal
      tumors.
AB  - BACKGROUND: The genetic mechanisms for families who meet the clinical criteria
      for Lynch syndrome (LS) but do not carry pathogenic variants in the mismatch
      repair (MMR) genes are still undetermined. We aimed to study the potential
      contribution of genes other than MMR genes to the biological and clinical
      characteristics of Norwegian families fulfilling Amsterdam (AMS) criteria or
      revised Bethesda guidelines. METHODS: The Hereditary Cancer Biobank of the
      Norwegian Radium Hospital was interrogated to identify individuals with a high
      risk of developing colorectal cancer (CRC) for whom no pathogenic variants in MMR
      genes had been found in routine diagnostic DNA sequencing. Forty-four cancer
      susceptibility genes were selected and analyzed by using our in-house designed
      TruSeq amplicon-based assay for targeted sequencing. RNA splicing- and protein
      dedicated in silico analyses were performed for all variants of unknown
      significance (VUS). Variants predicted as likely to affect splicing were
      experimentally analyzed by resorting to minigene assays. RESULTS: We identified a
      patient who met the revised Bethesda guidelines and carried a likely pathogenic
      variant in CHEK2 (c.470 T > C, p.I157T). In addition, 25 unique VUS were
      identified in 18 individuals, of which 2 exonic variants (MAP3K1 c.764A > G and
      NOTCH3 c.5854G >A) were analyzed in the minigene splicing assay and found not to
      have an effect on RNA splicing. CONCLUSIONS: Among high-risk CRC patients that
      fulfill the AMS criteria or revised Bethesda guidelines, targeted gene sequencing
      identified likely pathogenic variant and VUS in other genes than the MMR genes
      (CHEK2, NOTCH3 and MAP3K1). Our study suggests that the analysis of genes
      currently excluded from routine molecular diagnostic screens may confer cancer
      susceptibility.

PMID- 29458334
TI  - Identification of novel L2HGDH mutation in a large consanguineous Pakistani
      family- a case report.
AB  - BACKGROUND: L-2-hydroxyglutaric aciduria (L2HGA) is a progressive neurometabolic
      disease of brain caused by mutations of in L-2-hydroxyglutarate dehydrogenase
      (L2HGDH) gene. Cardinal clinical features include cerebellar ataxia, epilepsy,
      neurodevelopmental delay, intellectual disability, and other clinical
      neurological deficits. CASE PRESENTATION: We describe an index case of the family
      presented with generalised tonic-clonic seizure, developmental delay,
      intellectual disability, and ataxia. Initially, the differential diagnosis was
      difficult to be established and a SNP genome wide scan identified the candidate
      region on chromosome 14q22.1. DNA sequencing showed a novel homozygous mutation
      in the candidate gene L2HGDH (NM_024884.2: c.178G > A; p.Gly60Arg). The mutation
      p.Gly60Arg lies in the highly conserved FAD/NAD(P)-binding domain of this
      mitochondrial enzyme, predicted to disturb enzymatic function. CONCLUSIONS: The
      combination of homozygosity mapping and DNA sequencing identified a novel
      mutation in Pakistani family with variable clinical features. This is second
      report of a mutation in L2HGDH gene from Pakistan and the largest family with
      L2HGA reported to date.

PMID- 29458335
TI  - Integrated children's clinic care (ICCC) versus a self-directed care pathway for
      children with a chronic health condition: a multi-centre randomised controlled
      trial study protocol.
AB  - BACKGROUND: Children with chronic health conditions have better health-related
      outcomes when their care is managed in a personalised and coordinated way.
      However, increased demand on Australian ambulatory care hospital services has led
      to longer waitlist times to access specialists and appropriate intervention
      services; placing vulnerable children at increased risk of poorer short-term
      (e.g. social difficulties) and long-term (e.g. convictions) health and social
      outcomes. Traditional approaches to increasing frequency and service of delivery
      are expensive and can have minimal impact on caregiver burden. A community based
      service-integration approach, rather than self-directed care is proposed as
      increased service linkages are more likely to occur and improve the health
      outcomes of children with a chronic health condition. METHODS: An open,
      unblinded, multi-centre randomised controlled trial in two Australian public
      hospitals. 112 children (0-16 years) fulfilling the inclusion criteria will be
      randomised to one of two clinical pathways for management of their chronic health
      condition: (1) integrated children's care clinic (ICCC) or (2) self-directed care
      pathway. All children and caregivers will be interviewed at 1 week, and 3, 6 and
      12 month time intervals. Primary outcome measures include the Pediatric Quality
      of Life (PedQOL) questionnaire, Subjective Units of Distress Scale, Child
      Behaviour Checklist (CBCL) and Rotter's Locus of Control Scale. Secondary outcome
      measures include the total number of medical appointments, school days missed and
      quantity of services accessed. Our main objectives are to determine if the ICCC
      results in better health and economics outcomes compared to the self-directed
      care pathway. DISCUSSION: The success of a health systems approach needs to be
      balanced against clinical, mortality and cost-effectiveness data for long-term
      sustainability within a publicly funded health system. A clinical pathway that is
      sustainable, cost-effective, provides efficient evidence-based care and improves
      the quality of life outcomes for children with chronic health conditions has the
      potential to reduce waitlist times, improve access to health services, increase
      consumer satisfaction; and prevent costs associated with poorly managed chronic
      health conditions into adulthood. This study will be the first to provide
      clinical and health economics data on an integrated care pathway for the
      management of chronic health conditions in children. On a broader scale, results
      from this study will help guide care coordination frameworks for children with
      chronic health conditions; particularly with the introduction and implementation
      of a National Disability Insurance Scheme (NDIS) across Australia. TRIAL
      REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR)
      ACTRN12617001188325 . Registered: 14th August, 2017.

PMID- 29458336
TI  - Prevalence, aetiologies and prognosis of the symptom dizziness in primary care -
      a systematic review.
AB  - BACKGROUND: Dizziness is a common reason for consulting a general practitioner
      and there is a broad range of possible underlying aetiologies. There are few
      evidence-based data about prevalence, aetiology and prognosis in primary care. We
      aimed to conduct a systematic review of symptom-evaluating studies on prevalence,
      aetiology or prognosis of dizziness in primary care. METHODS: We systematically
      searched MEDLINE and EMBASE. Two independent researchers screened titles and
      abstracts according to predefined criteria. We included all studies evaluating
      the symptoms 'dizziness' or 'vertigo' as a reason for consultation in primary
      care. We extracted data about study population and methodology and prevalence,
      aetiology and prognosis. Two raters independently judged study quality and risk
      of bias. We investigated the variation across studies using forest plots, I2 and
      prediction intervals. Since we anticipated a great amount of clinical and
      unexplained statistical heterogeneity, we provided qualitative syntheses instead
      of pooled estimates. RESULTS: We identified 31 studies (22 on prevalence, 14 on
      aetiology and 8 on prognosis). Consultation prevalence differs between 1,0 and
      15,5%. The most common aetiologies are vestibular/peripheral (5,4-42,1%), benign
      peripheral positional vertigo (4,3-39,5%), vestibular neuritis (0,6-24,0%),
      Meniere's disease (1,4-2,7%), cardiovascular disease (3,8-56,8%), neurological
      disease (1,4-11,4%), psychogenic (1,8-21,6%), no clear diagnosis (0,0-80,2%).
      While studies based on subjective patient assessment reported improvement rates
      from 37 to 77%, these findings could not be confirmed when applying instruments
      that measure symptom severity or quality of life. CONCLUSION: There is a broad
      variety of possible underlying diseases for the symptom dizziness. There exist
      only few methodologically sound studies concerning aetiology and prognosis of
      dizziness.

PMID- 29458337
TI  - HIV-1 transmission and survival according to feeding options in infants born to
      HIV-infected women in Yaounde, Cameroon.
AB  - BACKGROUND: Evidence of 24-months survival in the frame of prevention of mother
      to-child transmission (PMTCT) cascade-care is scare from routine programs in sub
      Saharan African (SSA) settings. Specifically, data on infant outcomes according
      to feeding options remain largely unknown by month-24, thus limiting its breath
      for public-health recommendations toward eliminating new pediatric HIV-1
      infections and improving care. We sought to evaluate HIV-1 vertical transmission
      and infant survival rates according to feeding options. METHODS: A retrospective
      cohort-study conducted in Yaounde from April 2008 through December 2013 among
      1086 infants born to HIV-infected women and followed-up throughout the PMTCT
      cascade-care until 24-months. Infants with documented feeding option during their
      first 3 months of life (408 on Exclusive Breastfeeding [EBF], 663 Exclusive
      Replacement feeding [ERF], 15 mixed feeding [MF]) and known HIV-status were
      enrolled. HIV-1 vertical transmission, survival and feeding options were analyzed
      using Kaplan Meier Survival Estimate, Cox model and Schoenfeld residuals tests,
      at 5% statistical significance. RESULTS: Overall HIV-1 vertical transmission was
      3.59% (39), and varied by feeding options: EBF (2.70%), ERF (3.77%), MF (20%), p
      = 0.002; without significance between EBF and ERF (p = 0.34). As expected, HIV-1
      transmission also varied with PMTCT-interventions: 1.7% (10/566) from ART-group,
      1.9% (8/411) from AZT-group, and 19.2% (21/109) from ARV-naive group, p < 0.0001.
      Overall mortality was 2.58% (28), higher in HIV-infected (10.25%) vs. uninfected
      (2.29%) infants (p = 0.016); with a survival cumulative probability of 89.3%
      [79.9%-99.8%] vs. 96.4% [94.8%-97.9% respectively], p = 0.024. Mortality also
      varied by feeding option: ERF (2.41%), EBF (2.45%), MF (13.33%), p = 0.03; with a
      survival cumulative probability of 96% [94%-98%] in ERF, 96.4% [94.1%-98.8%] in
      EBF, and 86.67% [71.06%-100%] in MF, p = 0.04. Using Schoenfeld residuals test,
      only HIV status was a predictor of survival at 24 months (hazard ratio 0.23
      [0.072-0.72], p = 0.01). CONCLUSION: Besides using ART for PMTCT-interventions,
      practice of MF also drives HIV-1 vertical transmission and mortality among HIV
      infected children. Thus, throughout PMTCT option B+ cascade-care, continuous
      counseling on safer feeding options would to further eliminating new MTCT,
      optimizing response to care, and improving the life expectancy of these children
      in high-priority countries.

PMID- 29458338
TI  - Association of matrix metalloprotease 1, 3, and 12 polymorphisms with rheumatic
      heart disease in a Chinese Han population.
AB  - BACKGROUND: Rheumatic heart disease (RHD) is an autoimmune disease triggered by
      acute rheumatic fever (ARF). Matrix metalloproteinases (MMPs) play an important
      role in the modulation of immune responses. The purpose of this study was to
      evaluate the association of MMP1, 3, and 12 promoter polymorphisms with RHD in a
      Han population in Southern China since the 3 genes are localized on the same
      chromosome and have a combined effect. METHODS: DNA samples were obtained from 90
      adult patients with RHD and 90 control subjects. Polymorphisms in MMP1
      (rs1799750), MMP3 (rs3025058), and MMP12 (rs2276109) were genotyped by direct
      sequencing. Differences in genotype and allele frequencies of these polymorphisms
      were compared between the cases and the controls using Unconditional logistic
      regression models and Chi-squared test. RESULTS: The 2G/2G genotype of rs1799750
      in MMP1 was associated with a significantly higher risk of RHD when compared with
      the 1G/1G genotype (OR = 3.227; 95% CI:1.118-9.31; p = 0.03). The frequency of
      allele 2G was higher in patients with RHD compared to the controls (69.4% vs.
      58.9%; p = 0.048) No significant differences in genotype and allele frequencies
      of rs3025058 in MMP3 and rs2276109 in MMP12 were found between the patients with
      RHD and the controls (p > 0.05). CONCLUSIONS: Our results suggest that rs1799750
      in MMP1 might be a risk factor for RHD in a Han population in Southern China, and
      individuals carrying the 2G/2G genotype are likely more susceptible to RHD. In
      contrast, rs3025058 in MMP3 and rs2276109 in MMP12 might not contribute to the
      risk of developing RHD in this population. Further studies with larger samples
      and other ethnic populations are required to confirm these findings.

PMID- 29458339
TI  - Association of yield-related traits in founder genotypes and derivatives of
      common wheat (Triticum aestivum L.).
AB  - BACKGROUND: Yield improvement is an ever-important objective of wheat breeding.
      Studying and understanding the phenotypes and genotypes of yield-related traits
      has potential for genetic improvement of crops. RESULTS: The genotypes of 215
      wheat cultivars including 11 founder parents and 106 derivatives were analyzed by
      the 9 K wheat SNP iSelect assay. A total of 4138 polymorphic single nucleotide
      polymorphism (SNP) loci were detected on 21 chromosomes, of which 3792 were
      mapped to single chromosome locations. All genotypes were phenotyped for six
      yield-related traits including plant height (PH), spike length (SL), spikelet
      number per spike (SNPS), kernel number per spike (KNPS), kernel weight per spike
      (KWPS), and thousand kernel weight (TKW) in six irrigated environments. Genome
      wide association analysis detected 117 significant associations of 76 SNPs on 15
      chromosomes with phenotypic explanation rates (R 2 ) ranging from 2.03 to 12.76%.
      In comparing allelic variation between founder parents and their derivatives
      (106) and other cultivars (98) using the 76 associated SNPs, we found that the
      region 116.0-133.2 cM on chromosome 5A in founder parents and derivatives carried
      alleles positively influencing kernel weight per spike (KWPS), rarely found in
      other cultivars. CONCLUSION: The identified favorable alleles could mark
      important chromosome regions in derivatives that were inherited from founder
      parents. Our results unravel the genetic of yield in founder genotypes, and
      provide tools for marker-assisted selection for yield improvement.

PMID- 29458341
TI  - Correction to: Preferred prenatal counselling at the limits of viability: a
      survey among Dutch perinatal professionals.
AB  - CORRECTION: Following publication of the original article [1], the corresponding
      authors wrote to say that there was a mistake in the transfer of her article to
      PubMed: her name is R Geurtzen, but the pdf-file names her as ms R Geurtzen and
      pubmed names her as MR Geurtzen.

PMID- 29458340
TI  - A microbiome case-control study of recurrent acute otitis media identified
      potentially protective bacterial genera.
AB  - BACKGROUND: Recurrent acute otitis media (rAOM, recurrent ear infection) is a
      common childhood disease caused by bacteria termed otopathogens, for which
      current treatments have limited effectiveness. Generic probiotic therapies have
      shown promise, but seem to lack specificity. We hypothesised that healthy
      children with no history of AOM carry protective commensal bacteria that could be
      translated into a specific probiotic therapy to break the cycle of re-infection.
      We characterised the nasopharyngeal microbiome of these children (controls) in
      comparison to children with rAOM (cases) to identify potentially protective
      bacteria. As some children with rAOM do not appear to carry any of the known
      otopathogens, we also hypothesised that characterisation of the middle ear
      microbiome could identify novel otopathogens, which may also guide the
      development of more effective therapies. RESULTS: Middle ear fluids, middle ear
      rinses and ear canal swabs from the cases and nasopharyngeal swabs from both
      groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of
      cases and controls were distinct. We observed a significantly higher abundance of
      Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus,
      Staphylococcus and Turicella were abundant in the middle ear and ear canal of
      cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria
      were characteristic of the case nasopharynx, but were not prevalent in the middle
      ear. CONCLUSIONS: Corynebacterium and Dolosigranulum are characteristic of a
      healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are
      possible novel otopathogens, though their rarity in the nasopharynx and
      prevalence in the ear canal means that their role as normal aural flora cannot be
      ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do
      not appear to colonise the middle ear in children with rAOM.

PMID- 29458342
TI  - Maternal socio-demographic and psychological predictors for risk of developmental
      delays among young children in Mongolia.
AB  - BACKGROUND: Factors influencing child development are not well studied in
      developing settings, and especially in Mongolia. This cohort study examined the
      relationship between maternal socio-demographic and psychological conditions on
      risk of young child developmental delay. METHODS: A total of 150 children aged
      between 13 ~ 24 months old participated in this study. The participants were
      randomly selected from a pre-existing cohort of 1297 children who were involved
      in a study on infant bilirubin nomogram development conducted at a tertiary
      health facility in Mongolia between 2012 and 2013. Child development was
      evaluated using the Mongolian Rapid Baby Scale (MORBAS), a validated scale for
      child development. The potential factors for child developmental delay were
      assessed using a pre-tested questionnaire comprising of 52 questions. Fisher's
      exact test and multivariable logistic regression analysis were conducted.
      RESULTS: Seventeen (11%) out of the 150 children that participated in the study
      were at risk of developmental delay. There was a negative association between the
      risk of child developmental delay and higher maternal education (AOR 0.15, 95%
      CI: 0.03-0.66). Increasing maternal age (AOR 1.12, 95%CI: 0.98-1.27), maternal
      depression symptoms (AOR 4.93, 95%CI: 0.93-26.10), child gender being female (AOR
      0.25, 95%CI: 0.06-1.00) and being from single mother household (AOR 0.14, 95%CI:
      0.01-1.11) were also predictors for risk of developmental delay - although the
      association was marginal. CONCLUSIONS: Our findings suggest that being of
      underprivileged social status, and poor psychological condition of mothers in
      Mongolia possibly increases the risk of child developmental delays. Interventions
      targeting these modifiable predictors are needed to develop prevention strategies
      for child developmental delay.

PMID- 29458343
TI  - Factors affecting first month adherence due to antiretroviral therapy among HIV
      positive adults at Felege Hiwot Teaching and Specialized Hospital, north-western
      Ethiopia; a prospective study.
AB  - BACKGROUND: Non-adherence to Highly Active Antiretroviral Therapy (HAART) is one
      of the factors for treatment failure in human immunodeficiency virus (HIV)
      infected patients in developing countries. The main objective of this study was
      to identify factors for treatment failure among adult HIV patients based on the
      assessment of first month adherence in the study area. METHODS: The study was
      conducted using secondary data from antiretroviral unit at Felege Hiwot Teaching
      and Specialized Hospital. A prospective study was undertaken on 792 randomly
      selected adult HIV positive patients who have started HAART. The variable of
      interest, adherence to HAART was categorized as non-adherence if a patient had
      taken less than 95% of the prescribed medication and this was measured using pill
      counts. Descriptive statistics, Chi-square tests of association, independent
      samples t-test and binary logistic regression were used for data analysis.
      RESULTS: In first month therapy, 68.2% of the patients belong to adherence group
      to HAART. As age increases, a patient without cell phone was less likely to be
      adherent to HAART as compared to patients with cell phone (AOR = 0.661, 95% CI:
      (0.243, 0.964)). Compared to urban patients, rural patients were less likely to
      adhere to HAART (AOR = 0.995, 95% CI: (0.403, 0.999)). A patient who did not
      disclose his/her disease to families or communities had less probability to be
      adherent to HAART (AOR = 0.325, 95% CI: (0.01, 0.64)). Similarly, a patient who
      did not get social support (AOR = 0.42, 95% CI: (0,021, 0.473)) had less
      probability of adherence to HAART. The main reasons for patients to be non
      adherent were forgetfulness, side effects, feeling sick and running out of
      medication. CONCLUSION: This study indentified certain groups of patients who are
      at higher risk and who need counseling. Such groups should be targeted and
      tailored for improvement of adherence to HAART among HIV positive adults. The
      health care providers should advise the community to provide social support to
      HIV positive patients whenever their disease is disclosed. On the other hand,
      patients should disclose their disease to community to get integrated supports.
      HIV infected patients who are directed to start HAART should adhere the
      prescribed medication. For the adherence to be effective, patients who have cell
      phone should use them as reminder to take pills on time.

PMID- 29458344
TI  - The DEsire to DIe in Palliative care: Optimization of Management (DEDIPOM) - a
      study protocol.
AB  - BACKGROUND: A desire to die (DD) is frequent in palliative care (PC). However,
      uncertainty remains as to the appropriate therapeutic response. (Proactive)
      discussion of DD is not usually part of standard care. To support health
      practitioners' (HPs) reactions to a patient's DD, a training program has been
      developed, piloted and evaluated. Within this framework, a first draft of a semi
      structured clinical interview schedule with prompts (CISP) has been developed,
      including recommendations for action to support HPs' self-confidence. The aim of
      this study is the further development of the CISP to support routine exploration
      of death and dying distress and proactive addressing of a DD. METHODS: This
      observatory, prospective health services study comprises a three step study
      design: 1. Revision of the CISP and consensus finding based on semi-structured
      interviews with patients and a Delphi process with (inter-)national experts,
      patient representatives and relatives; 2. Increasing confidence in HPs through a
      2 day-training program using the consented CISP; 3. A formative quantitative
      evaluation of conversations between HPs and patients (300 palliative patients at
      three time points) and a qualitative evaluation based on interview triads of
      patients, relatives and HPs. The evaluation of conversations will include patient
      oriented outcomes, including perceived relationships with HPs and death and dying
      distress. We will also consider aspects of social inequality and gender.
      DISCUSSION: The intervention can provide a framework for open discussion of DD
      and a basis for enhancing a trustful HP-patient relationship in which such
      difficult topics can be addressed. The benefits of this study will include (a)
      the creation of the first consented semi-structured approach to identify and
      address DD and to respond therapeutically, (b) the multi-professional enhancement
      of confidence in dealing with patients' DD and an intervention that can flexibly
      be integrated into other training and education programs and (c) an evaluation of
      effects of this intervention on patients, relatives and HPs, with attention to
      social inequality and gender. TRIAL REGISTRATION: The study is registered in the
      German Clinical Trials Register ( DRKS00012988 ; registration date: 27.9.2017)
      and in the Health Services Research Database ( VfD_DEDIPOM_17_003889 ;
      registration date: 14.9.2017).

PMID- 29458345
TI  - Genetic polymorphisms in bone morphogenetic protein receptor type IA gene
      predisposes individuals to ossification of the posterior longitudinal ligament of
      the cervical spine via the smad signaling pathway.
AB  - BACKGROUND: The present study investigated the molecular mechanisms underlying
      the 4A > C and -349C > T single nucleotide polymorphisms (SNPs) in bone
      morphogenetic protein receptor type IA (BMPR-IA) gene, which significantly
      associated with the occurrence and the extent of ossification of the posterior
      longitudinal ligament (OPLL) in the cervical spine. METHODS: The SNPs in BMPR-IA
      gene were genotyped, and the association with the occurrence and severity of OPLL
      were evaluated in 356 OPLL patients and 617 non-OPLL controls. In stably
      transfected mouse embryonic mesenchymal stem cells (C3H10T1/2), the expression
      levels of the BMPR-IA gene and Smad4 protein as well as phosphorylated Smad1/5/8
      were detected by Western blotting. In addition, the alkaline phosphatase (ALP)
      and osteocalcin (OC) activity of osteogenesis specificity protein was assessed
      using the ALP quantitation and osteocalcin radioimmunoassay kit, respectively.
      RESULTS: The 4A > C and the -349C > T polymorphisms of BMPR-IA gene were
      significantly associated with the development of OPLL in the cervical spine. The
      C allele type in 4A > C polymorphism significantly increases the occurrence and
      the extent of OPLL. The T allele type in -349C > T polymorphism significantly
      increases the susceptibility to OPLL, but not the extent of OPLL. The current
      results further validate our previous observations. The expression levels of BMPR
      IA gene were significantly increased in pcDNA3.1/BMPR-IA (mutation type, MT -349C
      > T; MT 4A > C; MT -349C > T and 4A > C) vector-transfected C3H10T1/2 cells
      compared to the wild type (WT) vector-transfected cells. The levels of
      phosphorylated Smad1/5/8 and ALP activity were significantly increased in
      pcDNA3.1/BMPR-IA (MT -349C > T) vector-transfected C3H10T1/2 cells compared to
      the WT vector-transfected cells. However, no significant differences were
      observed in the protein levels of phosphorylated Smad1/5/8 and the ALP activity
      between MT A/C and WT vector-transfected cells. In addition, no significant
      differences were observed in the Smad4 protein levels among the experimental
      groups, as well as in the OC activity between WT vector-transfected and MT C/T,
      MT A/C, MT C/T and MT A/C vector-transfected cells. CONCLUSIONS: Our results
      suggest that Smad signaling pathway may play important roles in the pathological
      process of OPLL induced by SNPs in BMPR-IA gene. These results will help to
      clarify the molecular mechanisms underlying the SNP and gene susceptibility to
      OPLL.

PMID- 29458346
TI  - Associations between ERalpha/beta gene polymorphisms and osteoporosis
      susceptibility and bone mineral density in postmenopausal women: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Many studies have reported associations between estrogen receptor
      (ER) gene polymorphisms and postmenopausal osteoporosis (PMOP) risk and bone
      mineral density (BMD), but the results are controversial. The aim of the present
      meta-analysis is to verify the association between ERalpha and ERbeta gene
      polymorphisms and osteoporosis susceptibility and BMD in postmenopausal women.
      METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library and China WeiPu
      Library were searched. OR and WMD with 95% CI were calculated to assess the
      association. RESULTS: Overall, no significant association was observed between
      ERalpha XbaI, ERalpha PvuII and PMOP susceptibility in either overall, Caucasian
      or Asian populations. ERalpha G2014A was significantly associated with a
      decreased risk of PMOP in Caucasian populations. There was a significant
      association between ERbeta RsaI and PMOP risk in both overall and Asian
      populations. Caucasian PMOP women with ERalpha XbaI XX and Xx genotypes had a
      higher LS Z value than women with xx genotype. ERalpha XbaI XX genotype was
      associated with increased FN BMD in overall and Caucasian populations, an
      increased FN Z value in Asians, and a decreased FN Z value in Caucasians. There
      was also a significant association between ERalpha XbaI Xx genotype and an
      increased FN Z value in either Asians or Caucasians. ERalpha PvuII PP genotype
      was associated with a low LS Z value in Caucasians and a low FN BMD and Z value
      in Asians. Pp genotype in PMOP women was significantly correlated with low LS BMD
      in overall populations, a low FN Z value in either overall, Caucasian or Asian
      populations. CONCLUSION: Each ERalpha and ERbeta gene polymorphism might have
      different impact on PMOP risk and BMD in various ethnicities.

PMID- 29458347
TI  - The contribution of a MOOC to community discussions around death and dying.
AB  - BACKGROUND: Advances in medicine have helped many to live longer lives and to be
      able to meet health challenges. However death rates are anticipated to increase
      given the ageing population and chronic disease progression. Being able to talk
      about death is seen to be important in normalising death as part of life and
      supporting preparedness for death. Massive Open Online Courses (MOOCs) provide
      opportunities for the community to engage in collaborative learning. A 5 week
      MOOC was developed covering four main topics (language and humour,
      representations of death, medicalisation of dying, and digital dying) aiming: To
      enable participants to openly and supportively discuss and learn about issues
      around living, death and dying, To explore the normally unheard opinions and
      views of Australians around death and dying, and To determine what effect online
      learning and discussions offered through the MOOC had on participants' feelings
      and attitudes towards death and dying. METHODS: Data was captured on engagement
      rates in the various MOOC activities. Death Attitudes were measured by five items
      representing the MOOC's learning objectives and completed at enrolment and
      conclusion. MOOC Satisfaction was measured with six items at the end of the MOOC.
      Descriptive statistics were produced for each variable and Chi-Square Tests of
      Independence assessed the extent of the relationship between categorical
      variables. Socio-demographic variables were examined as predictors of the outcome
      variables of MOOC engagement, MOOC satisfaction, and death attitudes. Ethical
      approval was received from Flinders University Social and Behavioural Research
      Ethics Committee (Project No. 7247). RESULTS: One thousand one hundred fifty six
      people enrolled in the Dying2Learn MOOC with 895 participating in some way.
      Enrolees were primarily female (92.1%). Age ranged from 16 to 84 (mean = 49.5, SD
      = 12.3). MOOC satisfaction scores were high. Responses to the experience of
      participating in the MOOC were very positive, with mean scores ranging from 4.3
      to 4.6 (aligning with agreement and strong agreement to statements on the value
      of participating). Death Attitudes were positive at commencement but increased
      significantly following participation. CONCLUSIONS: The Dying2Learn MOOC provided
      an environment that enabled open and supportive discussion around death and dying
      and influenced attitudinal change.

PMID- 29458348
TI  - Patients' and caregivers' experiences of using continuous glucose monitoring to
      support diabetes self-management: qualitative study.
AB  - BACKGROUND: Continuous glucose monitoring (CGM) enables users to view real-time
      interstitial glucose readings and provides information on the direction and rate
      of change of blood glucose levels. Users can also access historical data to
      inform treatment decisions. While the clinical and psychological benefits of CGM
      are well established, little is known about how individuals use CGM to inform
      diabetes self-management. We explored participants' experiences of using CGM in
      order to provide recommendations for supporting individuals to make optimal use
      of this technology. METHODS: In-depth interviews (n = 24) with adults,
      adolescents and parents who had used CGM for >=4 weeks; data were analysed
      thematically. RESULTS: Participants found CGM an empowering tool because they
      could access blood glucose data effortlessly, and trend arrows enabled them to
      see whether blood glucose was rising or dropping and at what speed. This
      predicative information aided short-term lifestyle planning and enabled
      individuals to take action to prevent hypoglycaemia and hyperglycaemia. Having
      easy access to blood glucose data on a continuous basis also allowed participants
      to develop a better understanding of how insulin, activity and food impacted on
      blood glucose. This understanding was described as motivating individuals to make
      dietary changes and break cycles of over-treating hypoglycaemia and
      hyperglycaemia. Participants also described how historical CGM data provided a
      more nuanced picture of blood glucose control than was possible with blood
      glucose self-monitoring and, hence, better information to inform changes to
      background insulin doses and mealtime ratios. However, while participants
      expressed confidence making immediate adjustments to insulin and lifestyle to
      address impending hypoglycaemia and hypoglycaemia, most described needing and
      expecting health professionals to interpret historical CGM data and determine
      changes to background insulin doses and mealtime ratios. While alarms could
      reinforce a sense of hypoglycaemic safety, some individuals expressed ambivalent
      views, especially those who perceived alarms as signalling personal failure to
      achieve optimal glycaemic control. CONCLUSIONS: CGM can be an empowering and
      motivational tool which enables participants to fine-tune and optimize their
      blood glucose control. However, individuals may benefit from psycho-social
      education, training and/or technological support to make optimal use of CGM data
      and use alarms appropriately.

PMID- 29458349
TI  - Role of health determinants in a measles outbreak in Ecuador: a case-control
      study with aggregated data.
AB  - BACKGROUND: In 2011-2012, an outbreak of measles occurred in Ecuador. This study
      sought to ascertain which population characteristics were associated. METHODS:
      Case-control study of aggregate data. The unit of analysis was the parish
      (smallest geographic division). The national communicable disease surveillance
      database was used to identify 52 case parishes (with at least one confirmed case
      of measles) and 972 control parishes (no cases of measles). A hierarchical model
      was used to determine the association of measles with population characteristics
      and access to health care. RESULTS: Case parishes were mostly urban and had a
      higher proportion of children under 1 year of age, heads of household with higher
      educational attainment, larger indigenous population, lower rates of measles
      immunization, and lower rates of antenatal care visit attendance. On multivariate
      analysis, associations were found with educational attainment of head of
      household >=8 years (OR: 0.29; 95%CI 0.15-0.57) and >=1.4% indigenous population
      (OR: 3.29; 95%CI 1.63-6.68). Antenatal care visit attendance had a protective
      effect against measles (OR: 0.98; 95%CI 0.97-0.99). Measles vaccination was
      protective of the outbreak (OR: 0.97; 95%CI 0.95-0.98). The magnitude of these
      associations was modest, but represents the effect of single protective factors,
      capable of acting at the population level regardless of socioeconomic,
      biological, and environmental confounding factors. CONCLUSION: In Ecuador, the
      parishes with the highest percentage of indigenous populations and those with the
      lowest vaccination coverage were the most vulnerable during the measles outbreak.

PMID- 29458350
TI  - Obesity and risk of respiratory tract infections: results of an infection-diary
      based cohort study.
AB  - BACKGROUND: Respiratory tract infections (RTIs) are a major morbidity factor
      contributing largely to health care costs and individual quality of life. The aim
      of the study was to test whether obesity (BMI >= 30 kg/m2) is one of the risk
      factors underlying frequent RTIs in the German adult population. METHODS: We
      recruited 1455 individuals between 18 to 70 years from a cross-sectional survey
      on airway infections in Germany and invited them to self-report in diaries
      incident RTIs experienced during three consecutive winter/spring seasons. RTIs
      reported in these 18 months and summary measures adding-up individual RTIs were
      the outcomes of interest. RESULTS: Compared to individuals with normal weight,
      obese individuals reported a consistently higher frequency of upper and lower
      RTIs and predominantly fell in the upper 10% group of a diary sumscore adding-up
      10 different RTI symptoms over time. Obesity was associated both with lower RTIs
      (adjustedOR = 2.02, 95%CI = 1.36-3.00) and upper RTIs (adjustedOR = 1.55, 95%CI =
      1.22-1.96). Adjusting for demographic and lifestyle variables did only marginally
      affect ORs. Stratified analyses suggested a stronger association for women and
      effect modifications by sports activity and dietary habits. CONCLUSIONS: We
      confirm the association of obesity with infection burden and present evidence for
      putative interaction with sports activity and dietary patterns.

PMID- 29458351
TI  - CEMiTool: a Bioconductor package for performing comprehensive modular co
      expression analyses.
AB  - BACKGROUND: The analysis of modular gene co-expression networks is a well
      established method commonly used for discovering the systems-level functionality
      of genes. In addition, these studies provide a basis for the discovery of
      clinically relevant molecular pathways underlying different diseases and
      conditions. RESULTS: In this paper, we present a fast and easy-to-use
      Bioconductor package named CEMiTool that unifies the discovery and the analysis
      of co-expression modules. Using the same real datasets, we demonstrate that
      CEMiTool outperforms existing tools, and provides unique results in a user
      friendly html report with high quality graphs. Among its features, our tool
      evaluates whether modules contain genes that are over-represented by specific
      pathways or that are altered in a specific sample group, as well as it integrates
      transcriptomic data with interactome information, identifying the potential hubs
      on each network. We successfully applied CEMiTool to over 1000 transcriptome
      datasets, and to a new RNA-seq dataset of patients infected with Leishmania,
      revealing novel insights of the disease's physiopathology. CONCLUSION: The
      CEMiTool R package provides users with an easy-to-use method to automatically
      implement gene co-expression network analyses, obtain key information about the
      discovered gene modules using additional downstream analyses and retrieve
      publication-ready results via a high-quality interactive report.

PMID- 29458353
TI  - Isolated unilateral temporalis muscle hypertrophy in a child: a case report with
      literature review.
AB  - BACKGROUND: Temporalis muscle hypertrophy is a rare entity of masticatory muscle
      hypertrophy. All types of masticatory muscle hypertrophies have been documented
      of which temporalis muscle hypertrophy is one. Temporalis muscle hypertrophy is
      most commonly bilateral and usually associated with other types of masticatory
      muscles hypertrophy such as masseter or pterygoid hypertrophy. However, isolated
      unilateral temporalis muscle hypertrophy is extremely rare and only 9 cases have
      been reported to date in English literature since 1990 with only two patients
      less than 18 years. There is no exact etiology identified and the diagnosis is
      made by muscle biopsy combined with imaging study to exclude other possibilities.
      Age at presentation is ranges from 15 to 65 years with involvement of both sexes.
      We report the youngest child who is a seven year old girl with right side
      isolated unilateral temporalis muscle hypertrophy. CASE PRESENTATION: In this
      patient, we discuss the youngest child with isolated unilateral temporalis muscle
      hypertrophy and literature review to date. The patient is a seven year old female
      presenting with painless swelling of the right temporalis muscle. There had no
      features of inflammation, trauma, neoplasm or history of parafunctions such as
      bruxism. The child was not complaining significantly headache or visual
      disturbances as well. She had undergone radiological assessment with ultrasound
      scan and contrast MRI. The diagnosis was confirmed by muscle biopsy which shows
      normal muscle architecture. She was managed conservatively with regular follow
      up. CONCLUSION: Isolated unilateral temporalis muscle hypertrophy is extremely
      rare in children. However this case raises the importance of considering
      alternative diagnoses despite the condition being rare in the pediatric
      population.

PMID- 29458352
TI  - Reducing GHG emissions while improving diet quality: exploring the potential of
      reduced meat, cheese and alcoholic and soft drinks consumption at specific
      moments during the day.
AB  - BACKGROUND: The typical Western diet is associated with high levels of greenhouse
      gas (GHG) emissions and with obesity and other diet-related diseases. This study
      aims to determine the impact of adjustments to the current diet at specific
      moments of food consumption, to lower GHG emissions and improve diet quality.
      METHODS: Food consumption in the Netherlands was assessed by two non-consecutive
      24-h recalls for adults aged 19-69 years (n = 2102). GHG emission of food
      consumption was evaluated with the use of life cycle assessments. The population
      was stratified by gender and according to tertiles of dietary GHG emission.
      Scenarios were developed to lower GHG emissions of people in the highest tertile
      of dietary GHG emission; 1) reducing red and processed meat consumed during
      dinner by 50% and 75%, 2) replacing 50% and 100% of alcoholic and soft drinks
      (including fruit and vegetable juice and mineral water) by tap water, 3)
      replacing cheese consumed in between meals by plant-based alternatives and 4) two
      combinations of these scenarios. Effects on GHG emission as well as nutrient
      content of the diet were assessed. RESULTS: The mean habitual daily dietary GHG
      emission in the highest tertile of dietary GHG emission was 6.7 kg CO2
      equivalents for men and 5.1 kg CO2-equivalents for women. The scenarios with
      reduced meat consumption and/or replacement of all alcoholic and soft drinks were
      most successful in reducing dietary GHG emissions (ranging from - 15% to - 34%)
      and also reduced saturated fatty acid intake and/or sugar intake. Both types of
      scenarios lead to reduced energy and iron intakes. Protein intake remained
      adequate. CONCLUSIONS: Reducing the consumption of red and processed meat during
      dinner and of soft and alcoholic drinks throughout the day leads to significantly
      lower dietary GHG emissions of people in the Netherlands in the highest tertile
      of dietary GHG emissions, while also having health benefits. For subgroups of the
      population not meeting energy or iron requirements as a result of these dietary
      changes, low GHG emission and nutritious replacement foods might be needed in
      order to meet energy and iron requirements.

PMID- 29458355
TI  - Healthy Parent Carers programme: development and feasibility of a novel group
      based health-promotion intervention.
AB  - BACKGROUND: Parent carers of disabled children report poor physical health and
      mental wellbeing. They experience high levels of stress and barriers to
      engagement in health-related behaviours and with 'standard' preventive programmes
      (e.g. weight loss programmes). Interventions promoting strategies to improve
      health and wellbeing of parent carers are needed, tailored to their specific
      needs and circumstances. METHODS: We developed a group-based health promotion
      intervention for parent carers by following six steps of the established
      Intervention Mapping approach. Parent carers co-created the intervention
      programme and were involved in all stages of the development and testing. We
      conducted a study of the intervention with a group of parent carers to examine
      the feasibility and acceptability. Standardised questionnaires were used to
      assess health and wellbeing pre and post-intervention and at 2 month follow up.
      Participants provided feedback after each session and took part in a focus group
      after the end of the programme. RESULTS: The group-based Healthy Parent Carers
      programme was developed to improve health and wellbeing through engagement with
      eight achievable behaviours (CLANGERS - Connect, Learn, be Active, take Notice,
      Give, Eat well, Relax, Sleep), and by promoting empowerment and resilience. The
      manualised intervention was delivered by two peer facilitators to a group of
      seven parent carers. Feedback from participants and facilitators was strongly
      positive. The study was not powered or designed to test effectiveness but changes
      in measures of participants' wellbeing and depression were in a positive
      direction both at the end of the intervention and 2 months later which suggest
      that there may be a potential to achieve benefit. CONCLUSIONS: The Healthy Parent
      Carers programme appears feasible and acceptable. It was valued by, and was
      perceived to have benefited participants. The results will underpin future
      refinement of the intervention and plans for evaluation.

PMID- 29458354
TI  - The slowdown of Y chromosome expansion in dioecious Silene latifolia due to DNA
      loss and male-specific silencing of retrotransposons.
AB  - BACKGROUND: The rise and fall of the Y chromosome was demonstrated in animals but
      plants often possess the large evolutionarily young Y chromosome that is thought
      has expanded recently. Break-even points dividing expansion and shrinkage phase
      of plant Y chromosome evolution are still to be determined. To assess the size
      dynamics of the Y chromosome, we studied intraspecific genome size variation and
      genome composition of male and female individuals in a dioecious plant Silene
      latifolia, a well-established model for sex-chromosomes evolution. RESULTS: Our
      genome size data are the first to demonstrate that regardless of intraspecific
      genome size variation, Y chromosome has retained its size in S. latifolia.
      Bioinformatics study of genome composition showed that constancy of Y chromosome
      size was caused by Y chromosome DNA loss and the female-specific proliferation of
      recently active dominant retrotransposons. We show that several families of
      retrotransposons have contributed to genome size variation but not to Y
      chromosome size change. CONCLUSIONS: Our results suggest that the large Y
      chromosome of S. latifolia has slowed down or stopped its expansion. Female
      specific proliferation of retrotransposons, enlarging the genome with exception
      of the Y chromosome, was probably caused by silencing of highly active
      retrotransposons in males and represents an adaptive mechanism to suppress
      degenerative processes in the haploid stage. Sex specific silencing of
      transposons might be widespread in plants but hidden in traditional
      hermaphroditic model plants.

PMID- 29458357
TI  - Genomic screening for monogenic forms of diabetes.
AB  - Adult-onset, or type II diabetes mellitus (T2DM) has a complex genetic
      architecture, from hundreds of genes with low penetrance, common susceptibility
      variants (e.g., TCF7L2), to a set of more than ten genes that, when mutated, can
      cause a single-gene or Mendelian form of T2DM (e.g., GCK). It is a clinical
      challenge to identify patients with the uncommon (2-3%) form of T2DM, typically
      classified as maturity-onset diabetes of the young (MODY). Bansal et al. (BMC Med
      15:213, 2017) used a gene panel test approach to test patients with diabetes for
      single-gene causes of MODY. They found that nearly 2% of younger patients had
      pathogenic variants in one of seven genes. These data confirm prior studies
      showing that Mendelian or single-gene MODY can masquerade as garden variety T2DM.
      The implications of these results for wider general medicine and the future
      implementation of clinical genome sequencing are discussed.Please see related
      article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0977
      3.

PMID- 29458356
TI  - Prevalence of attention-deficit/hyperactivity disorder symptoms and their
      associations with sleep schedules and sleep-related problems among preschoolers
      in mainland China.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) among children is an
      increasing public health concern. The identification of behavioral risk factors,
      including sleep quality, has important public health implications for
      prioritizing behavioral intervention strategies for ADHD. Herein, this study
      aimed to investigate the prevalence of high levels of ADHD symptoms and to
      explore the association between sleep schedules, sleep-related problems and ADHD
      symptoms among preschoolers aged 3 to 6 years in mainland China. METHODS: A cross
      sectional study was conducted, comprising a large sample of 15,291 preschoolers
      in Ma'anshan city of Anhui Province in China. ADHD symptoms were assessed by the
      10-item Chinese version of the Conners Abbreviated Symptom Questionnaire (C-ASQ).
      Sleep-related variables included caregivers' responses to specific questions
      addressing children's daytime and nighttime sleep schedules, as well as sleep
      related behaviors. Data on other factors were also collected, such as socio
      demographic characteristics, TV viewing duration on weekdays and weekends, and
      outdoor activities. Logistic regression models were used to analyze the
      relationships between sleep schedules, sleep-related problems and ADHD symptoms.
      RESULTS: Approximately 8.6% of the total sample of preschoolers had high levels
      of ADHD symptoms, with boys having higher levels than girls (9.9% vs. 7.2%). In
      the logistic regression analysis, after adjusting for TV viewing duration,
      outdoor activities, and socio-demographic characteristics, delayed bedtime was
      significantly associated with a risk of high levels of ADHD symptoms, with odds
      ratios (OR) of 2.50 [95% confidence interval (CI): 2.09 ~ 3.00] and 2.04 (95% CI:
      1.72 ~ 2.42) for weekdays and weekends, respectively. Longer time falling asleep
      (>= 31 min) (OR = 1.76, 95% CI: 1.47 ~ 2.11), no naps (OR = 1.57, 95% CI: 1.34 ~
      1.84) and frequent sleep-related problems (OR = 4.57, 95% CI: 3.86 ~ 5.41) were
      also significantly associated with an increased risk of high levels of ADHD
      symptoms, while longer sleep duration (> 8.5 h) was associated with a decreased
      risk of high levels of ADHD symptoms (OR = 0.76, 95% CI: 0.67~ 0.87).
      CONCLUSIONS: ADHD symptoms are prevalent in preschoolers in Ma'anshan region,
      China. Undesirable sleep schedules and sleep-related problems among preschoolers
      confer a risk of ADHD symptoms, highlighting the finding that beneficial and
      regular sleep habits potentially attenuate ADHD symptoms among preschoolers.

PMID- 29458358
TI  - Effective behavioral intervention strategies using mobile health applications for
      chronic disease management: a systematic review.
AB  - BACKGROUND: Mobile health (mHealth) has continuously been used as a method in
      behavioral research to improve self-management in patients with chronic diseases.
      However, the evidence of its effectiveness in chronic disease management in the
      adult population is still lacking. We conducted a systematic review to examine
      the effectiveness of mHealth interventions on process measures as well as health
      outcomes in randomized controlled trials (RCTs) to improve chronic disease
      management. METHODS: Relevant randomized controlled studies that were published
      between January 2005 and March 2016 were searched in six databases: PubMed,
      CINAHL, EMBASE, the Cochrane Library, PsycINFO, and Web of Science. The inclusion
      criteria were RCTs that conducted an intervention using mobile devices such as
      smartphones or tablets for adult patients with chronic diseases to examine
      disease management or health promotion. RESULTS: Of the 12 RCTs reviewed, 10 of
      the mHealth interventions demonstrated statistically significant improvement in
      some health outcomes. The most common features of mHealth systems used in the
      reviewed RCTs were real-time or regular basis symptom assessments, pre-programed
      reminders, or feedbacks tailored specifically to the data provided by
      participants via mHealth devices. Most studies developed their own mHealth
      systems including mobile apps. Training of mHealth systems was provided to
      participants in person or through paper-based instructions. None of the studies
      reported the relationship between health outcomes and patient engagement levels
      on the mHealth system. CONCLUSIONS: Findings from mHealth intervention studies
      for chronic disease management have shown promising aspects, particularly in
      improving self-management and some health outcomes.

PMID- 29458359
TI  - In-utero exposure to phenols and phthalates and the intelligence quotient of boys
      at 5 years.
AB  - BACKGROUND: There are concerns that developmental exposure to endocrine
      disrupting chemicals such as phenolic compounds and phthalates could affect child
      cognitive function. Epidemiological studies tackling this question have mainly
      focused on phthalate metabolites and bisphenol A, but not on the other phenolic
      compounds. Our study aimed to assess the relationship between in-utero exposure
      to phthalates, bisphenol A and other phenolic compounds (parabens, triclosan,
      dichlorophenols and benzophenone-3) and the Intelligence Quotient (IQ) of boys at
      5-6 years. METHODS: In 452 mother-son dyads from the French EDEN cohort, we
      measured 11 phthalate metabolites and 9 phenolic compounds (4 parabens,
      benzophenone-3, bisphenol A, 2 dichlorophenols and triclosan) in spot urine
      samples collected between 22 and 29 gestational weeks. Verbal and performance IQ
      of children were assessed at 5-6 years by a psychologist using the Wechsler
      Preschool and Primary Scale of Intelligence (WPPSI). We used adjusted Structural
      Equation Models (SEM) combined with Benjamini and Hochberg false discovery rate
      correction to assess the associations between maternal urine phenol and phthalate
      metabolite concentrations considered simultaneously and the boys' IQ. RESULTS: No
      phenol or phthalate metabolite concentration was negatively associated with the
      boys' verbal or performance IQ (uncorrected p-values >=0.09). Mono(3
      carboxypropyl) phthalate tended to be associated with increased verbal IQ (beta =
      0.136, 95% confidence interval, 0.01; 0.27). This association disappeared after
      correction for multiple comparison (corrected p-value, 0.71). CONCLUSION: Our
      results did not provide evidence of an inverse association between in-utero
      exposure to phenols or phthalates and verbal and performance IQ among boys. Since
      phenols and phthalates may have sex-specific effects, these null findings cannot
      be generalized to girls. Limitations included use of a single spot urine sample
      to assess exposures and lack of consideration of postnatal exposures.

PMID- 29458360
TI  - Care-'less': exploring the interface between child care and parental control in
      the context of child rights for workers in children's homes in Ghana.
AB  - BACKGROUND: This study explored how employed caregivers experience the interface
      between child care, parental control and child rights in the context of
      Children's Homes in Ghana. The focus was on investigating caregiver perceptions
      of proper child care, their experiences with having to work with child rights
      principles and the implication of these for their relationships with the children
      and the care services they deliver. METHODS: Adopting a qualitative approach with
      phenomenological design, data were collected from 41 caregivers in two children's
      homes in Ghana using focus group discussions and in-depth interviews. RESULTS: It
      emerged that caregivers experienced frustrations with perceived limitations that
      child rights principles place on their control over the children describing it as
      lessening and, at the same time, complicating the care services they provide.
      CONCLUSIONS: The findings suggest a need for a review of the implementation
      strategies of the child rights approach in that context. A re-organization of the
      children's homes environment and re-orientation of caregivers and children
      regarding their relationship is also suggested.

PMID- 29458361
TI  - Health services in Trinidad: throughput, throughput challenges, and the impact of
      a throughput intervention on overcrowding in a public health institution.
AB  - BACKGROUND: Throughput might be partially responsible for sub-optimum
      organisational and medical outcomes. The present study examined throughput and
      the challenges to ensuring optimum throughput in hospitals, and determined the
      effectiveness of a throughput intervention in reducing overcrowding in a public
      healthcare institution in Trinidad and Tobago. METHODS: First, a literature
      review of throughput and its processes in relation to improving hospital care was
      conducted. Second, the challenges to throughput in healthcare were reviewed. Data
      were also collected from print media, hospital records, and the central
      statistical office in Trinidad and Tobago to discuss throughput and describe the
      throughput status in hospitals. Finally, the effect of a throughput intervention
      on overcrowding was determined. The intervention was implemented over six months,
      from October 2010 to March 2011, and comprised three stages of a five-stage
      throughput process: transferring patients to a specific medical ward, bedside
      electrocardiograms (ECG), and promptly obtaining patient investigative reports
      and patient files. RESULTS: Problems with the throughput process led to prolonged
      delays or failures in obtaining lab reports, radiology services, ECGs, and
      pharmaceutical supplies, as well as inadequate social work services and other
      specialised services. During the throughput intervention, there was a reduction
      in overcrowding/overflow to 5-10 patients per day with a daily admission rate of
      58. However, at post-intervention, there was increased overcrowding/overflow to
      20-30 per day but fewer admissions (52 per day) i.e. similar to pre-intervention
      period. Additionally, there was an increase in bed complement in the department
      of medicine from 209 (2011) to 227 (2012). Overcrowding continued into 2016 and
      beyond: medical admissions in 2016 were 46.4 per day and the medical bed capacity
      was 327 (indicating a 44% increase in capacity from 2012). CONCLUSION: Hospital
      throughput processes are currently suboptimum. Improving specific throughput
      processes or targeting the greatest primary constraints might help decrease
      overcrowding.

PMID- 29458362
TI  - Correction to: An audit of clinical training exposure amongst junior doctors
      working in Trauma & Orthopaedic Surgery in 101 hospitals in the United Kingdom.
AB  - CORRECTION: Following publication of the original article [1], the corresponding
      author wrote to say that he had missed the names of some of the collaborators in
      the list he sent to the typesetters. In addition, there was a spelling error in
      one of the author's names: instead of Nagriz Seyidova it should read Nargiz
      Seyidova. The complete list of collaborators is as follows.

PMID- 29458363
TI  - Rollout of rapid point of care tests for antenatal syphilis screening in Ghana:
      healthcare provider perspectives and experiences.
AB  - BACKGROUND: Effective implementation of rapid point of care tests (POCTs) for
      antenatal syphilis screening especially in settings where antenatal care
      attendance is high, can significantly increase screening coverage and treatment
      uptake. The operational challenges of introducing rapid syphilis POCTs at scale
      needs to be investigated. This study explores healthcare providers' experiences
      and challenges in antenatal syphilis screening following the national rollout of
      rapid syphilis POCTs in Ghana. METHODS: Prior to the main study, we undertook a
      desk review of key syphilis policy documents, and conducted key stakeholder
      interviews and a baseline survey of syphilis screening practices. Antenatal
      syphilis screening had been poorly implemented mainly due to inadequate technical
      and logistic support, and lack of monitoring and supervision. For the main
      research, semi-structured interviews were conducted with 51 purposively selected
      healthcare staff involved in antenatal syphilis screening in 15 health facilities
      in three regions, representative of all levels of healthcare in Ghana and two
      regional programme coordinators, at least four months after the rollout. The
      interviews were supplemented with an audit of the conduct of antenatal care,
      syphilis-related supplies and other maternal and newborn interventions.
      Qualitative data were coded and analysed using Nvivo software. RESULTS: Syphilis
      screening with rapid POCTs was integrated into antenatal care in almost all
      (13/15) the facilities surveyed. Testing and treatment were offered free of
      charge to pregnant women, their partners and babies. In most facilities, midwives
      were performing syphilis tests together with HIV tests. Operational challenges
      included: inadequate training and lack of refresher training, lack of clear
      testing guidelines, clear channels of communication, supervision, and guidance on
      treatment and referral procedures, frequent stockouts of, or expired test kits,
      staff overload, and poor documentation of test results and treatment. CONCLUSION:
      Although syphilis screening with rapid syphilis POCTs was integrated into
      antenatal care, key challenges, particularly around supply chain and supervision,
      need to be addressed to improve and sustain such a programme.

PMID- 29458364
TI  - Transgenerational effects of polychlorinated biphenyls: 1. Development and
      physiology across 3 generations of rats.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) are persistent organic environmental
      contaminants and known endocrine-disrupting chemicals (EDCs). Previous studies
      demonstrated that developmental exposure to the weakly estrogenic PCB mixture
      Aroclor 1221 (A1221) in Sprague-Dawley rats altered sexual development, adult
      reproductive physiology and body weight. The current study tested the hypothesis
      that prenatal A1221 exposure not only disrupts these endpoints within an exposed
      individual's (F1 generation) lifespan, but may also affect subsequent generations
      (F2-F3). METHODS: We treated pregnant female rats on embryonic days (E) 16 and
      E18 with A1221 (1 mg/kg), estradiol benzoate (50 MUg/kg, positive estrogenic
      control), or vehicle (3% DMSO in sesame oil, negative control). Endpoints related
      to sexually dimorphic developmental trajectories of reproductive and
      developmental physiology were measured, and as adults, reproductive endocrine
      status was assessed, in the F1, F2, and F3 generations. RESULTS: Significant
      effects of transgenerational EDCs were found for body weight and serum hormones.
      The A1221 descendants had significantly higher body weight in the F2-maternal
      lineage throughout postnatal development, and in F3-maternal lineage animals
      after weaning. In females, generation- and lineage-specific effects of exposure
      were found for serum progesterone and estradiol. Specifically, serum progesterone
      concentrations were lower in F2-A1221 females, and higher in F3-A1221 females,
      compared to their respective F2- and F3-vehicle counterparts. Serum estradiol
      concentrations were higher in F3-A1221 than F3-vehicle females. Reproductive and
      adrenal organ weights, birth outcomes, sex ratio, and estrous cycles, were
      unaffected. It is notable that effects of A1221 were only sometimes mirrored by
      the estrogenic control, EB, indicating that the mechanism of action of A1221 was
      likely via non-estrogenic pathways. CONCLUSIONS: PCBs caused body weight and
      hormonal effects in rats that were not observed in the directly exposed F1
      offspring, but emerged in F2 and F3 generations. Furthermore, most effects were
      in the maternal lineage; this may relate to the timing of exposure of the F1
      fetuses at E16 and 18, when germline (the future F2 generation) epigenetic
      changes diverge in the sexes. These results showing transgenerational effects of
      EDCs have implications for humans, as we are now in the 3rd generation since the
      Chemical Revolution of the mid-twentieth century, and even banned chemicals such
      as PCBs have a persistent imprint on the health of our descendants.

PMID- 29458366
TI  - Inequity in dialysis related practices and outcomes in Aotearoa/New Zealand: a
      Kaupapa Maori analysis.
AB  - BACKGROUND: In Aotearoa/New Zealand, Maori, as the indigenous people, experience
      chronic kidney disease at three times the rate of non-Maori, non-Pacific New
      Zealanders. Maori commence dialysis treatment for end-stage kidney disease at
      three times the rate of New Zealand European adults. To examine for evidence of
      inequity in dialysis-related incidence, treatment practices, and survival
      according to indigeneity in Aotearoa/New Zealand, utilising a Kaupapa Maori
      approach. METHODS: We conducted a retrospective cohort study involving adults who
      commenced treatment for end-stage kidney disease in Aotearoa/New Zealand between
      2002 and 2011. We extracted data from the Australian and New Zealand Dialysis and
      Transplant Registry (ANZDATA) linked to the New Zealand National Health Index
      (NHI). Propensity score methods were used to assemble a cohort of 1039 Maori
      patients matched 1:1 on clinical and socio-demographic characteristics with a
      cohort of 1026 non-Maori patients. We compared incidence of end-stage kidney
      disease and treatment practices. Differences in the risks of all-cause mortality
      during treatment between propensity-matched cohorts were estimated using Cox
      proportional hazards and generalised linear models. RESULTS: Non-Maori patients
      were older, more frequently lived in urban areas (83% versus 67% [standardised
      difference 0.38]) and bore less socioeconomic deprivation (36% living in highest
      decile areas versus 14% [0.53]). Fewer non-Maori patients had diabetes (35%
      versus 69%, [- 0.72]) as a cause of kidney failure. Non-Maori patients were more
      frequently treated with peritoneal dialysis (34% versus 29% [0.11]), received a
      pre-emptive kidney transplant (4% vs 1% [0.19]), and were referred to specialist
      care < 3 months before treatment (25% vs 19% [0.15]) than Maori patients. Fewer
      non-Maori started dialysis with a non-tunnelled dialysis vascular catheter (43%
      versus 47% [- 0.08]). The indigenous-age standardised incidence rate ratio for
      non-Maori commencing renal replacement therapy in 2011 was 0.50 (95% CI, 0.40
      0.61) compared with Maori. Propensity score matching generated cohorts with
      similar characteristics, although non-Maori less frequently started dialysis with
      a non-tunnelled venous catheter (30% versus 47% [- 0.35]) or lived remotely (3%
      versus 14% [- 0.50]). In matched cohorts, non-Maori experienced lower all-cause
      mortality at 5 yr. after commencement of treatment (risk ratio 0.78, 95% CI 0.72
      0.84). New Zealand European patients experienced lower mortality than Maori
      patients in indigenous age-standardised analyses (age-standardised mortality rate
      ratio 0.58, 95% CI 0.51-0.67). CONCLUSIONS: Non-Maori patients are treated with
      temporary dialysis vascular access less often than Maori, and experience longer
      life expectancy with dialysis, even when socioeconomic, demographic, and
      geographical factors are equivalent. Based on these disparities, health services
      should monitor and address inequitable treatment practices and outcomes in end
      stage kidney disease care.

PMID- 29458365
TI  - Temporal changes in genetic diversity of msp-1, msp-2, and msp-3 in Plasmodium
      falciparum isolates from Grande Comore Island after introduction of ACT.
AB  - BACKGROUND: Malaria is still one of the serious public health problems in Grande
      Comore Island, although the number of annual cases has been greatly reduced in
      recent years. A better understanding of malaria parasite population diversity and
      transmission dynamics is critical for assessing the effectiveness of malaria
      control measures. The objective of this study is to investigate temporal changes
      in genetic diversity of Plasmodium falciparum populations and multiplicity of
      infection (MOI) in Grande Comore 10 years after introduction of ACT. METHODS: A
      total of 232 P. falciparum clinical isolates were collected from the Grande
      Comore Island during two sampling periods (118 for 2006-2007 group, and 114 for
      2013-2016 group). Parasite isolates were characterized for genetic diversity and
      complexity of infection by genotyping polymorphic regions in merozoite surface
      protein gene 1 (msp-1), msp-2, and msp-3 using nested PCR and DNA sequencing.
      RESULTS: Three msp-1 alleles (K1, MAD20, and RO33), two msp-2 alleles (FC27 and
      3D7), and two msp-3 alleles (K1 and 3D7) were detected in parasites of both
      sampling periods. The RO33 allele of msp-1 (84.8%), 3D7 allele of msp-2 (90.8%),
      and K1 allele of msp-3 (66.7%) were the predominant allelic types in isolates
      from 2006-2007 group. In contrast, the RO33 allele of msp-1 (63.4%), FC27 allele
      of msp-2 (91.1%), and 3D7 allele of msp-3 (53.5%) were the most prevalent among
      isolates from the 2013-2016 group. Compared with the 2006-2007 group, polyclonal
      infection rates of msp-1 (from 76.7 to 29.1%, P < 0.01) and msp-2 (from 62.4 to
      28.3%, P < 0.01) allelic types were significantly decreased in those from 2013
      2016 group. Similarly, the MOIs for both msp-1 and msp-2 were higher in P.
      falciparum isolates in the 2006-2007 group than those in 2013-2016 group (MOI =
      3.11 vs 1.63 for msp-1; MOI = 2.75 vs 1.35 for msp-2). DNA sequencing analyses
      also revealed reduced numbers of distinct sequence variants in the three genes
      from 2006-2007 to 2013-2016: msp-1, from 32 to 23 (about 28% decline); msp-2 from
      29 to 21 (about 28% decline), and msp-3 from 11 to 3 (about 72% decline).
      CONCLUSIONS: The present data showed dramatic reduction in genetic diversity and
      MOI among Grande Comore P. falciparum populations over the course of the study,
      suggesting a trend of decreasing malaria transmission intensity and genetic
      diversity in Grande Comore Island. These data provide valuable information for
      surveillance of P. falciparum infection and for assessing the appropriateness of
      the current malarial control strategies in the endemic area.

PMID- 29458367
TI  - The rs1024611 in the CCL2 gene and risk of gynecological cancer in Asians: a meta
      analysis.
AB  - BACKGROUND: The -2518A/G (rs1024611) polymorphism of the CCL2 (C-C motif
      chemokine ligand 2), also known as MCP-1 (monocyte chemotactic protein-1) gene,
      has been reported to be associated with increased gynecological cancer risk, but
      the results are conflicting. METHODS: In this analysis, 1089 cases and 1553
      controls from six publications were used to investigate the association between
      CCL2-2518A/G (rs1024611) polymorphism and the risk of gynecological cancer with a
      meta-analytic approach. Studies published on EBSCO, EMBASE, Web of Science,
      PubMed, SpringerLink, ScienceDirect, Weipu, and CNKI databases were identified
      (last update was on November 3, 2015). Six articles focused on the association
      between CCL2-2518A/G (rs1024611) polymorphism, and gynecological cancer risk was
      selected and data were extracted. The cancer type included endometrial cancer (n
      = 1), breast cancer (n = 2), ovarian cancer (n = 2), and cervical cancer (n = 1).
      All statistical analyses were performed using the STATA version 12.0 software.
      RESULTS: The meta-analysis showed that CCL2-2518A/G (rs1024611) polymorphism is
      associated with risk of gynecological cancer (GG vs AG + AA, OR = 1.55, 95%CI =
      1.07-2.24, P < 0.05; AA vs GG, OR = 0.59 95%CI = 0.38-0.92, P < 0.05). Notably,
      the subgroup analysis demonstrated that the genotype AA is associated with a
      reduced gynecological cancer risk in Asians, but an increased risk when compared
      to AG in Europeans. CONCLUSIONS: Our data demonstrated the CCL2-2518A/G
      (rs1024611) polymorphism is significantly associated with risk of gynecological
      cancer, and the association differs by ethnicity.

PMID- 29458368
TI  - Report from the 3rd Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes &
      Cardiovascular Disease (D&CVD) EASD Study Group.
AB  - The 3rd Cardiovascular Outcome Trial Summit of the Diabetes & Cardiovascular
      Disease EASD Study Group was held on the 26-27 October 2017 in Munich. As in 2015
      and 2016, this summit was organised in light of recently completed and published
      CVOTs on diabetes, aiming to serve as a reference meeting for in-depth
      discussions on the topic. Amongst others, the CVOTs EXSCEL, DEVOTE, the CANVAS
      program and the ACE-trial, which released primary outcome results in 2017, were
      discussed. Trial implications for diabetes management and recent perspectives of
      diabetologists, cardiologists, endocrinologists, nephrologists and general
      practitioners were highlighted. The clinical relevance of cardiovascular outcome
      trials and its implications regarding reimbursement were compared with real-world
      studies. The 4th Cardiovascular Outcome Trial Summit will be held in Munich 25-26
      October 2018 ( http://www.dcvd.org ).

PMID- 29458369
TI  - Is fasting safe? A chart review of adverse events during medically supervised,
      water-only fasting.
AB  - BACKGROUND: Evidence suggests that fasting, during which only water is consumed,
      results in potentially health promoting physiological effects. However, peer
      reviewed research assessing the safety of water-only fasting is lacking. To
      address this, we conducted a chart review to describe adverse events (AEs) that
      occurred during medically supervised, water-only fasting. METHODS: Electronic
      charts from patient visits to a residential medical facility from 2006 to 2011
      were reviewed. Patients who were at least 21 years of age and water-only fasted
      for >=2 consecutive days with a refeeding period equal to half of the fast length
      were included. Out of 2539 charts, 768 visits met our inclusion and exclusion
      criteria. AEs were abstracted from chart notes and classified according to CTCAE
      (v4.03) and MedDRA (v12.1) terminology. Descriptive analysis of AEs is reported.
      RESULTS: During the protocol period, the highest grade AE (HGAE) in 555 visits
      was a grade 2 event or lower, in 212 visits it was a grade 3 event, in 1 visit it
      was a grade 4 event, and there were no grade 5 events. There were 2 (0.002%)
      visits with a serious adverse event (SAE). The majority of AEs identified were
      mild (n = 4490, 75%) in nature and known reactions to fasting. CONCLUSIONS: To
      our knowledge, this is the most comprehensive analysis of AEs experienced during
      medically supervised, water-only fasting conducted to date. Overall, our data
      indicate that the majority of AEs experienced were mild to moderate and known
      reactions to fasting. This suggests that the protocol used in this study can be
      safely implemented in a medical setting with minimal risk of a SAE.

PMID- 29458370
TI  - The critical roles of activated stellate cells-mediated paracrine signaling,
      metabolism and onco-immunology in pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant
      diseases worldwide. It is refractory to conventional treatments, and consequently
      has a documented 5-year survival rate as low as 7%. Increasing evidence indicates
      that activated pancreatic stellate cells (PSCs), one of the stromal components in
      tumor microenvironment (TME), play a crucial part in the desmoplasia,
      carcinogenesis, aggressiveness, metastasis associated with PDAC. Despite the
      current understanding of PSCs as a "partner in crime" to PDAC, detailed
      regulatory roles of PSCs and related microenvironment remain obscure. In addition
      to multiple paracrine signaling pathways, recent research has confirmed that PSCs
      mediated tumor microenvironment may influence behaviors of PDAC via diverse
      mechanisms, such as rewiring metabolic networks, suppressing immune responses.
      These new activities are closely linked with treatment and prognosis of PDAC. In
      this review, we discuss the recent advances regarding new functions of activated
      PSCs, including PSCs-cancer cells interaction, mechanisms involved in
      immunosuppressive regulation, and metabolic reprogramming. It's clear that these
      updated experimental or clinical studies of PSCs may provide a promising approach
      for PDAC treatment in the near future.

PMID- 29458371
TI  - Mechanisms of rapid cancer cell reprogramming initiated by targeted receptor
      tyrosine kinase inhibitors and inherent therapeutic vulnerabilities.
AB  - Receptor tyrosine kinase (RTK) pathways serve as frequent oncogene drivers in
      solid cancers and small molecule and antibody-based inhibitors have been
      developed as targeted therapeutics for many of these oncogenic RTKs. In general,
      these drugs, when delivered as single agents in a manner consistent with the
      principles of precision medicine, induce tumor shrinkage but rarely complete
      tumor elimination. Moreover, acquired resistance of treated tumors is nearly
      invariant such that monotherapy strategies with targeted RTK drugs fail to
      provide long-term control or cures. The mechanisms mediating acquired resistance
      in tumors at progression treated with RTK inhibitors are relatively well defined
      compared to the molecular and cellular understanding of the cancer cells that
      persist early on therapy. We and others propose that these persisting cancer
      cells, termed "residual disease", provide the reservoir from which acquired
      resistance eventually emerges. Herein, we will review the literature that
      describes rapid reprogramming induced upon inhibition of oncogenic RTKs in cancer
      cells as a mechanism by which cancer cells persist to yield residual disease and
      consider strategies for disrupting these intrinsic responses for future
      therapeutic gain.

PMID- 29458372
TI  - Relationship of CT-quantified emphysema, small airways disease and bronchial wall
      dimensions with physiological, inflammatory and infective measures in COPD.
AB  - BACKGROUND: COPD is a complex, heterogeneous disease characterised by progressive
      development of airflow limitation. Spirometry provides little information about
      key aspects of pathology and is poorly related to clinical outcome, so other
      tools are required to investigate the disease. We sought to explore the
      relationships between quantitative CT analysis with functional, inflammatory and
      infective assessments of disease to identify the utility of imaging to stratify
      disease to better predict outcomes and disease response. METHODS: Patients from
      the AERIS study with moderate-very severe COPD underwent HRCT, with image
      analysis determining the quantity of emphysema (%LAA<- 950), small airways
      disease (E/I MLD) and bronchial wall thickening (Pi10). At enrolment subjects
      underwent lung function testing, six-minute walk testing (6MWT), blood sampling
      for inflammatory markers and sputum sampling for white cell differential and
      microbiological culture and PCR. RESULTS: 122 subjects were included in this
      analysis. Emphysema and small airways disease had independent associations with
      airflow obstruction (beta = - 0.34, p < 0.001 and beta = - 0.56, p < 0.001).
      %LAA<- 950 had independent associations with gas transfer (beta = - 0.37, p <
      0.001) and E/I MLD with RV/TLC (beta = 0.30, p =0.003). The distance walked
      during the 6MWT was not associated with CT parameters, but exertional
      desaturation was independently associated with emphysema (beta = 0.73, p <
      0.001). Pi10 did not show any independent associations with lung function or
      functional parameters. No CT parameters had any associations with sputum
      inflammatory cells. Greater emphysema was associated with lower levels of
      systemic inflammation (CRP beta = - 0.34, p < 0.001 and fibrinogen beta = - 0.28,
      p =0.003). There was no significant difference in any of the CT parameters
      between subjects where potentially pathogenic bacteria were detected in sputum
      and those where it was not. CONCLUSIONS: This study provides further validation
      for the use of quantitative CT measures of emphysema and small airways disease in
      COPD as they showed strong associations with pulmonary physiology and functional
      status. In contrast to this quantitative CT measures showed few convincing
      associations with biological measures of disease, suggesting it is not an
      effective tool at measuring disease activity.

PMID- 29458373
TI  - Using PROMIS for measuring recovery after abdominal surgery: a pilot study.
AB  - BACKGROUND: To assess the construct validity and responsiveness of the PROMIS
      Physical Function v1.2 short form 8b (PROMIS-PF), and the PROMIS Ability to
      Participate in Social Roles and Activities v2.0 short form 8a (PROMIS-APS) in
      postoperative recovery. METHODS: An observational pilot study was conducted in
      which 30 patients participated, undergoing various forms of abdominal surgery.
      Patients completed the PROMIS-PF and PROMIS-APS, the Short Form 36 Health Survey
      (SF-36) and the World Health Organization Disability Assessment Schedule 2.0
      (WHODAS) at several time points before and after surgery. The construct validity
      and responsiveness of the two PROMIS short forms were evaluated by testing pre
      defined hypotheses and were considered adequate when at least 75% of the data was
      consistent with the hypotheses. Construct validity was evaluated by calculating
      Spearman correlations and the responsiveness by calculating effect sizes.
      RESULTS: 6/7 (85.7%) of the results were consistent with the hypotheses
      supporting the construct validity of the PROMIS-PF. For the PROMIS-APS this was
      the case in 7/15 (46.7%) of the results. For the PROMIS-PF, 6/7 (85.7%) of the
      results were consistent with the hypotheses, supporting responsiveness. Regarding
      the responsiveness of the PROMIS-APS, only 7 out of 13 (53.8%) of these results
      were consistent with the hypotheses. CONCLUSIONS: This study supported the
      construct validity and the responsiveness of the PROMIS-PF v1.2 short form 8b for
      measuring recovery in abdominal surgery. Considering the major advantages of
      PROMIS, we recommend the use of the PROMIS-PF in abdominal surgery.

PMID- 29458374
TI  - New insights into long noncoding RNAs and their roles in glioma.
AB  - Glioma is one of the most prevalent types of primary intracranial carcinoma with
      varying malignancy grades I-IV and histological subtypes, including astrocytomas,
      glioblastoma multiform (GBM), oligodendrogliomas and mixed tumors. Glioma is
      characterized by rapid cell proliferation and angiogenesis, and the WHO grade IV
      glioblastoma, which is highly malignant with poor prognosis because GBM stem-like
      cells (GSCs) are resistant to conventional therapy and easily recrudescent,
      accounts for the majority of gliomas. Consequently, investigations exploring the
      accurate molecular mechanisms and reliable therapeutic targets for gliomas have
      drawn extensive attention.Based on the increasing amount of functional lncRNAs
      aberrantly expressed in glioma tissues and cell lines, lncRNAs might be critical
      for glioma initiation, progression and other malignant phenotypes. This review
      summarizes the latest insights into the lncRNA field and their functional roles
      in glioma, therefore evaluating the potential clinical applications of lncRNAs as
      prospective novel biomarkers and therapeutic targets.

PMID- 29458375
TI  - Letter to editor: Blood pressure, hypertension and lead exposure.
AB  - A significant association of office diastolic blood pressure with low-level blood
      lead exposure was reported in a Brazilian adult population. However, caution
      should be taken to interpret these results. The multivariable-adjusted
      association with blood pressure was positive for diastolic blood pressure, but
      inverse for systolic blood pressure. The association sizes were infinitesimal
      without clinical relevance. The outcome measures, i.e. blood pressure and the
      prevalence of hypertension were analysed across categories of the blood lead
      distribution - not in relation to blood lead as continuous variable. Blood
      pressure was the average of two oscillometric office readings, whereas ambulatory
      monitoring is the state-of-the-art.

PMID- 29458376
TI  - High experienced continuity in breast cancer care is associated with high health
      related quality of life.
AB  - BACKGROUND: High experienced continuity is known to be associated with lower
      needs for supportive care and most likely higher quality of life. On this
      background, the aim of this study was to investigate if patient-experienced
      continuity of care was associated with health-related quality of life (HRQoL) in
      breast cancer patients treated at two different-sized breast cancer units.
      METHODS: In 2016, two questionnaires, "Statements on experienced continuity of
      care" and "The European Organisation for Research and Treatment of Cancer Quality
      of Life Questionnaire Core 30 (EORTC QLQ-C30)", were sent out to patients
      diagnosed between 2011 and 2014 at two different-sized breast cancer units in
      Sweden. Lead times and other data reflecting medical quality were collected from
      the patients' medical records and from the National Swedish Breast Cancer Quality
      Register. RESULTS: Of 356 eligible patients, 231 (65%) answered the
      questionnaires, of whom 218 patients were included in the analyses. A
      statistically significant association was found between high experienced
      continuity and high global HRQoL (p = 0.03). Continuity was higher at the smaller
      unit, while no major differences between the units were found regarding medical
      quality or lead times. CONCLUSION: The study found that high experienced
      continuity and HRQoL was strongly associated. A statistically significant higher
      continuity of care was found at the smaller unit, in line with what was expected.
      The absence of clinically relevant differences in lead times and medical quality
      may indicate that continuity could be achieved without loss of quality.

PMID- 29458378
TI  - Correction to: The role of oral co-trimoxazole in treating Nocardia farcinica
      keratitis: a case report.
AB  - CORRECTION: This article [1] was unintentionally published twice in this journal,
      by the same authors.

PMID- 29458377
TI  - Out-of-hospital cardiac arrest in the home: Can area characteristics identify at
      risk communities in the Republic of Ireland?
AB  - BACKGROUND: Internationally, the majority of out-of-hospital cardiac arrests
      where resuscitation is attempted (OHCAs) occur in private residential locations
      i.e. at home. The prospect of survival for this patient group is universally
      dismal. Understanding of the area-level factors that affect the incidence of OHCA
      at home may help national health planners when implementing community
      resuscitation training and services. METHODS: We performed spatial smoothing
      using Bayesian conditional autoregression on case data from the Irish OHCA
      register. We further corrected for correlated findings using area level variables
      extracted and constructed for national census data. RESULTS: We found that
      increasing deprivation was associated with increased case incidence. The
      methodology used also enabled us to identify specific areas with higher than
      expected case incidence. CONCLUSIONS: Our study demonstrates novel use of
      Bayesian conditional autoregression in quantifying area level risk of a health
      event with high mortality across an entire country with a diverse settlement
      pattern. It adds to the evidence that the likelihood of OHCA resuscitation events
      is associated with greater deprivation and suggests that area deprivation should
      be considered when planning resuscitation services. Finally, our study
      demonstrates the utility of Bayesian conditional autoregression as a
      methodological approach that could be applied in any country using registry data
      and area level census data.

PMID- 29458379
TI  - Factors associated with multiple barriers to access to primary care: an
      international analysis.
AB  - BACKGROUND: Disparities in access to primary care (PC) have been demonstrated
      within and between health systems. However, few studies have assessed the factors
      associated with multiple barriers to access occurring along the care-seeking
      process in different healthcare systems. METHODS: In this secondary analysis of
      the 2016 Commonwealth Fund International Health Policy Survey of Adults, access
      was represented through participant responses to questions relating to access
      barriers either before or after reaching the PC practice in 11 countries
      (Australia, Canada, France, Germany, Norway, the Netherlands, New Zealand,
      Sweden, Switzerland, the United Kingdom, and United States). The number of
      respondents in each country ranged from 1000 to 7000 and the response rates
      ranged from 11% to 47%. We used multivariable logistic regression models within
      each of eleven countries to identify disparities in response to the access
      barriers by age, sex, immigrant status, income and the presence of chronic
      conditions. RESULTS: Overall, one in five adults (21%) experienced multiple
      barriers before reaching PC practices. After reaching care, an average of 16% of
      adults had two or more barriers. There was a sixfold difference between nations
      in the experience of these barriers to access. Vulnerable groups experiencing
      multiple barriers were relatively consistent across countries. People with lower
      income were more likely to experience multiple barriers, particularly before
      reaching primary care practices. Respondents with mental health problems and
      those born outside the country displayed substantial vulnerability in terms of
      barriers after reaching care. CONCLUSION: A greater understanding of the multiple
      barriers to access to PC across the stages of the care-seeking process may help
      to inform planning and performance monitoring of disparities in access. Variation
      across countries may reveal organisational and system drivers of access, and
      inform efforts to improve access to PC for vulnerable groups. The cumulative
      nature of these barriers remains to be assessed.

PMID- 29458380
TI  - Prevalence of molecular markers of artemisinin and lumefantrine resistance among
      patients with uncomplicated Plasmodium falciparum malaria in three provinces in
      Angola, 2015.
AB  - BACKGROUND: Artemisinin-based combination therapy is the first-line anti-malarial
      treatment for uncomplicated Plasmodium falciparum infection in Angola. To date,
      the prevalence of polymorphisms in the pfk13 gene, associated with artemisinin
      resistance, and pfmdr1, associated with lumefantrine resistance, have not been
      systematically studied in Angola. METHODS: DNA was isolated from pretreatment and
      late treatment failure dried blood spots collected during the 2015 round of
      therapeutic efficacy studies in Benguela, Lunda Sul, and Zaire Provinces in
      Angola. The pfk13 propeller domain and pfmdr1 gene were sequenced and analysed
      for polymorphisms. Pfmdr1 copy number variation was assessed using a real-time
      PCR method. The association between pfmdr1 and pfk13 mutations and treatment
      failure was investigated. RESULTS: The majority of pretreatment (99%, 466/469)
      and all late treatment failure (100%, 50/50) samples were wild type for pfk13.
      Three of the pretreatment samples (1%) carried the A578S mutation commonly
      observed in Africa and not associated with artemisinin resistance. All 543
      pretreatment and day of late treatment failure samples successfully analysed for
      pfmdr1 copy number variation carried one copy of pfmdr1. The NYD haplotype was
      the predominant pfmdr1 haplotype, present in 63% (308/491) of pretreatment
      samples, followed by NFD, which was present in 32% (157/491) of pretreatment
      samples. The pfmdr1 N86 allele was overrepresented in day of late treatment
      failure samples from participants receiving artemether-lumefantrine (p value
      0.03). CONCLUSIONS: The pretreatment parasites in patients participating in
      therapeutic efficacy studies in 2015 in Angola's three sentinel sites showed
      genetic evidence of susceptibility to artemisinins, consistent with clinical
      outcome data showing greater than 99% day 3 clearance rates. The lack of
      increased pfmdr1 copy number is consistent with previous reports from sub-Saharan
      Africa. Although pfmdr1 NYD and NFD haplotypes were overrepresented in artemether
      lumefantrine late treatment failure samples, their role as markers of resistance
      was unclear given that these haplotypes were also present in the majority of
      successfully treated patients in the artemether-lumefantrine treatment arms.

PMID- 29458381
TI  - Cardiac fluid dynamics meets deformation imaging.
AB  - Cardiac function is about creating and sustaining blood in motion. This is
      achieved through a proper sequence of myocardial deformation whose final goal is
      that of creating flow. Deformation imaging provided valuable contributions to
      understanding cardiac mechanics; more recently, several studies evidenced the
      existence of an intimate relationship between cardiac function and intra
      ventricular fluid dynamics. This paper summarizes the recent advances in cardiac
      flow evaluations, highlighting its relationship with heart wall mechanics
      assessed through the newest techniques of deformation imaging and finally
      providing an opinion of the most promising clinical perspectives of this emerging
      field. It will be shown how fluid dynamics can integrate volumetric and
      deformation assessments to provide a further level of knowledge of cardiac
      mechanics.

PMID- 29458382
TI  - Cost-effectiveness of the treatment of uncomplicated severe acute malnutrition by
      community health workers compared to treatment provided at an outpatient facility
      in rural Mali.
AB  - BACKGROUND: The Malian Nutrition Division of the Ministry of Health and Action
      Against Hunger tested the feasibility of integrating treatment of severe acute
      malnutrition (SAM) into the existing Integrated Community Case Management package
      delivered by community health workers (CHWs). This study assessed costs and cost
      effectiveness of CHW-delivered care compared to outpatient facility-based care.
      METHODS: Activity-based costing methods were used, and a societal perspective
      employed to include all relevant costs incurred by institutions, beneficiaries
      and communities. The intervention and control arm enrolled different numbers of
      children so a modelled scenario sensitivity analysis was conducted to assess the
      cost-effectiveness of the two arms, assuming equal numbers of children enrolled.
      RESULTS: In the base case, with unequal numbers of children in each arm, for CHW
      delivered care, the cost per child treated was 244 USD and cost per child
      recovered was 259 USD. Outpatient facility-based care was less cost-effective at
      442 USD per child and 501 USD per child recovered. The conclusions of the
      analysis changed in the modelled scenario sensitivity analysis, with outpatient
      facility-based care being marginally more cost-effective (cost per child treated
      is 188 USD, cost per child recovered is 214 USD), compared to CHW-delivered care.
      This suggests that achieving good coverage is a key factor influencing cost
      effectiveness of CHWs delivering treatment for SAM in this setting. Per week of
      treatment, households receiving CHW-delivered care spent half of the time
      receiving treatment and three times less money compared with those receiving
      treatment from the outpatient facility. CONCLUSIONS: This study supports existing
      evidence that the delivery of treatment by CHWs is a cost-effective intervention,
      provided that good coverage is achieved. A major benefit of this strategy was the
      lower cost incurred by the beneficiary household when treatment is available in
      the community. Further research is needed on the implementation costs that would
      be incurred by the government to increase the operability of these results.

PMID- 29458383
TI  - Cumulative exposure to environmental pollutants during early pregnancy and
      reduced fetal growth: the Project Viva cohort.
AB  - BACKGROUND: Reduced fetal growth is associated with perinatal and later
      morbidity. Prenatal exposure to environmental pollutants is linked to reduced
      fetal growth at birth, but the impact of concomitant exposure to multiple
      pollutants is unclear. The purpose of this study was to examine interactions
      between early pregnancy exposure to cigarette smoke, traffic pollution, and
      select perfluoroalkyl substances (PFASs) on birth weight-for-gestational age
      (BW/GA). METHODS: Among 1597 Project Viva mother-infant pairs, we assessed
      maternal cigarette smoking by questionnaire, traffic pollution at residential
      address by black carbon land use regression model, and plasma concentration of
      select PFASs in early pregnancy. We calculated sex-specific BW/GA z-scores, an
      index of fetal growth, from national reference data. We fit covariate-adjusted
      multi-pollutant linear regression models and examined interactions between
      exposures, using a likelihood-ratio test to identify a best-fit model. RESULTS:
      Two hundred six (13%) mothers smoked during pregnancy. Mean [standard deviation
      (SD)] for black carbon was 0.8 (0.3) MUg/m3, perfluorooctane sulfonate (PFOS) was
      29.1 (16.5) ng/mL, and BW/GA z-score was 0.19 (0.96). In the best-fit model,
      BW/GA z-score was lower in infants of mothers exposed to greater black carbon [-
      0.08 (95% CI: -0.15, - 0.01) per interquartile range (IQR)]. BW/GA z-score (95%
      CI) was also lower in infants of mothers who smoked [- 0.09 (- 0.23, 0.06)] or
      were exposed to greater PFOS [- 0.03 (- 0.07, 0.02) per IQR], although confidence
      intervals crossed the null. There were no interactions between exposures. In
      secondary analyses, instead of PFOS, we examined perfluorononanoate (PFNA) [mean
      (SD): 0.7 (0.4) ng/mL], a PFAS more closely linked to lower BW/GA in our cohort.
      The best-fit multi-pollutant model included positive two-way interactions between
      PFNA and both black carbon and smoking (p-interactions = 0.03). CONCLUSIONS:
      Concurrent prenatal exposures to maternal smoking, black carbon, and PFOS are
      additively associated with lower fetal growth, whereas PFNA may attenuate
      associations of smoking and black carbon with lower fetal growth. It is important
      to examine interactions between multiple exposures in relation to health
      outcomes, as effects may not always be additive and may shed light on biological
      pathways.

PMID- 29458384
TI  - Cardiovascular cine imaging and flow evaluation using Fast Interrupted Steady
      State (FISS) magnetic resonance.
AB  - BACKGROUND: Existing cine imaging techniques rely on balanced steady-state free
      precession (bSSFP) or spoiled gradient-echo readouts, each of which has
      limitations. For instance, with bSSFP, artifacts occur from rapid through-plane
      flow and off-resonance effects. We hypothesized that a prototype cine technique,
      radial fast interrupted steady-state (FISS), could overcome these limitations.
      The technique was compared with standard cine bSSFP for cardiac function,
      coronary artery conspicuity, and aortic valve morphology. Given its advantageous
      properties, we further hypothesized that the cine FISS technique, in combination
      with arterial spin labeling (ASL), could provide an alternative to phase contrast
      for visualizing in-plane flow patterns within the aorta and branch vessels. MAIN
      BODY: The study was IRB-approved and subjects provided consent. Breath-hold cine
      FISS and bSSFP were acquired using similar imaging parameters. There was no
      significant difference in biplane left ventricular ejection fraction or cardiac
      image quality between the two techniques. Compared with cine bSSFP, cine FISS
      demonstrated a marked decrease in fat signal which improved conspicuity of the
      coronary arteries, while suppression of through-plane flow artifact on thin-slice
      cine FISS images improved visualization of the aortic valve. Banding artifacts in
      the subcutaneous tissues were reduced. In healthy subjects, dynamic flow patterns
      were well visualized in the aorta, coronary and renal arteries using cine FISS
      ASL, even when the slice was substantially thicker than the vessel diameter.
      CONCLUSION: Cine FISS demonstrates several benefits for cardiovascular imaging
      compared with cine bSSFP, including better suppression of fat signal and reduced
      artifacts from through-plane flow and off-resonance effects. The main drawback is
      a slight (~ 20%) decrease in temporal resolution. In addition, preliminary
      results suggest that cine FISS ASL provides a potential alternative to phase
      contrast techniques for in-plane flow quantification, while enabling an
      efficient, visually-appealing, semi-projective display of blood flow patterns
      throughout the course of an artery and its branches.

PMID- 29458385
TI  - De novo mast cell leukemia without CD25 expression and KIT mutations: a rare case
      report in a 13-year-old child.
AB  - BACKGROUND: Mast cell leukemia (MCL) is a very rare form of systemic mastocytosis
      (SM) and accounts for less than 0.5% of all mastocytosis. The diagnosis of MCL
      requires the presence of SM criteria, accompanied by leukemic infiltrating of
      atypical mast cells (MCs) in bone marrow (BM), peripheral blood as well as
      extracutaneous organs. MCL is a fatal disease that almost always behaves
      aggressively, and the median survival time is only about six months. Herein, we
      present a rare case of de novo MCL without CD25 expression and KIT mutations.
      CASE PRESENTATION: A previously healthy 13-year-old boy was referred to our
      hospital due to incidental discovery of an enlarged right tonsil. Diffuse
      infiltration of medium-sized hematopoietic blasts was found in his right tonsil,
      BM and multiple lymph nodes. The neoplastic cell population was subsequently
      revealed to exhibit differentiation towards the mast cell lineage by expressing
      CD117 and tryptase, but the cell population lacked expression of CD25/CD2 and the
      activating mutation of the KIT gene. An abnormal karyotype was identified, but no
      leukemia-associated fusion genes were found. Involvement of peripheral blood,
      bone and lung was subsequently demonstrated. The most important differential
      diagnosis included tryptase-positive (T+) acute myeloid leukemia, myelomastocytic
      leukemia and basophilic leukemia. The morphological characteristics and
      infiltrating patterns of the abnormal MCs supported the final diagnosis of MCL.
      Although intensive chemotherapy and allogeneic stem cell transplants were
      performed on the patient, he died 18 months after initial presentation.
      CONCLUSION: Due to its rarity, the diagnosis of MCL without typical
      immunophenotype and genetic aberrations is particularly challenging.
      Comprehensive investigation of clinical and pathological features to exclude
      other T+ myeloid neoplasms is necessary.

PMID- 29458386
TI  - Functional improvements in patients with lymphangioleiomyomatosis after
      sirolimus: an observational study.
AB  - BACKGROUND: Sirolimus has been shown to be effective in patients with
      lymphangioleiomyomatosis (LAM). We wish to summarize our experience using
      sirolimus and its effectiveness in LAM patients. METHODS: We analyzed data from
      98 patients who were diagnosed with definite or probable sporadic LAM based on
      the European Respiratory Society diagnosis criteria for LAM in 2010 at Peking
      Union Medical College Hospital and who had received sirolimus during January 2007
      to June 2015. The data before and after the initiation of sirolimus therapy
      included pulmonary function tests, arterial blood gas analysis, 6-min walking
      distance (6MWD), size of chylous effusion and renal angiomyolipomas (AML), St.
      George's Respiratory Questionnaires (SGRQ) and vascular endothelial growth factor
      D (VEGF-D) levels. Serum levels of sirolimus and adverse events were collected.
      RESULTS: Median follow-up was 2.5 years. Most patients had forced expiratory
      volume in 1 s (FEV1) values less than 70% predicted or symptomatic chylothorax.
      The mean changes before and after the initiation of sirolimus were - 31.12 +/-
      30.78 mL/month and 16.11 +/- 36.00 mL/month (n = 18,p = 0.002) for FEV1 change,
      and - 0.55 +/- 0.60 mmHg/month and 0.30 +/- 1.19 mmHg/month (n = 17, p = 0.018)
      for PaO2 change. 6MWD improved from 358.8 +/- 114.4 m to 415.6 +/- 118.6 m (n =
      46, p = 0.004) and SGRQ total score from 57.2 +/- 21.0 to 47.5 +/- 22.8 (n = 50,
      p < 0.001). The median VEGF-D concentration decreased to 1609.4 pg/mL from 3075.6
      pg/mL after sirolimus therapy (n = 41, p < 0.001). Patients with sirolimus trough
      levels of 5-9.9 ng/mL had an increase in FEV1 (p < 0.05). Sixty-five percent of
      patients (13/20) had almost complete resolution of chylous effusions. The most
      frequent adverse events were mouth ulcers, menstrual disorder, hyperlipidemia and
      acneiform rash, all were mild. CONCLUSION: Long-term use of sirolimus is safe in
      patients with LAM. LAM patients with FEV1 less than 70% predicted and symptomatic
      chylothorax are suitable for receiving sirolimus therapy. The maintaining serum
      trough levels of sirolimus are recommended between 5 to 9.99 ng/mL.

PMID- 29458387
TI  - Correction to: Biomechanical properties of 3D-printed bone scaffolds are improved
      by treatment with CRFP.
AB  - CORRECTION TO: J ORTHOP SURG RES (2017) 12: 195. HTTPS://DOI.ORG/10.1186/S13018
      017-0700-2: In the original publication of this article [1] there was an error in
      one of the author names. In this publication the correct and incorrect name are
      indicated.

PMID- 29458388
TI  - A novel generation 1928zT2 CAR T cells induce remission in extramedullary relapse
      of acute lymphoblastic leukemia.
AB  - BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T cells have shown promise
      in the treatment of B cell acute lymphocytic leukemia (B-ALL). However, its
      efficacy in B-ALL patients with extramedullary involvement is limited due to poor
      responses and neurotoxicity. Here, we utilized a third generation of CAR T cell
      vector, which contains the Toll/interleukin-1 receptor (ITR) domain of Toll-like
      receptor 2 (TLR2), to generate 1928zT2 T cells targeting CD19, and evaluated the
      efficacy of 1928zT2 T cells in relapse or refractory B-ALL patients with
      extramedullary involvement. METHODS: 1928zT2 T cells were generated by 19-28z
      TLR2 lentiviral vector transfection into primary human T lymphocytes. The anti
      leukemia effect of 1928zT2 T cells were determined by killing assays and in
      xenografts. Three patients diagnosed as relapse or refractory ALL with
      extramedullary involvement were infused with 1928zT2 T cells, and the clinical
      responses were evaluated by BM smear, B-ultrasonography, PET/CT, histology, flow
      cytometry, qPCR, ELISA, and luminex assay. RESULTS: 1928zT2 T cells exhibited
      enhanced effector function against CD19+ leukemic cells in vitro and in a
      xenograft model of human extramedullary leukemia. Notably, the 1928zT2 T cells
      eradicated extramedullary leukemia and induced complete remission in the three
      relapse and refractory ALL patients without serious adverse effects. 1928zT2 T
      cells expanded robustly in the circulation of these three patients and were
      detected in the cerebrospinal fluid of patient 3. These three patients
      experienced cytokine release syndrome (CRS) with grade 2 or 3, which remitted
      spontaneously or after tocilizumab treatment. None of the three patients suffered
      neurotoxicity or needed further intensive care. CONCLUSIONS: Our results
      demonstrate that 1928zT2 T cells with TLR2 incorporation augment anti-leukemic
      effects, particularly for eradicating extramedullary leukemia cells, and suggest
      that the infusion of 1928zT2 T cells is an encouraging treatment for
      relapsed/refractory ALL patients with extramedullary involvement. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier NCT02822326 . Date of registration:
      July 4, 2016.

PMID- 29458389
TI  - Artesunate shows potent anti-tumor activity in B-cell lymphoma.
AB  - BACKGROUND: Although chemo-immunotherapy has led to an improved overall survival
      for most B-cell lymphoma types, relapsed and refractory disease remains a
      challenge. The malaria drug artesunate has previously been identified as a growth
      suppressor in some cancer types and was tested as a new treatment option in B
      cell lymphoma. METHODS: We included artesunate in a cancer sensitivity drug
      screen in B lymphoma cell lines. The preclinical properties of artesunate was
      tested as single agent in vitro in 18 B-cell lymphoma cell lines representing
      different histologies and in vivo in an aggressive B-cell lymphoma xenograft
      model, using NSG mice. Artesunate-treated B lymphoma cell lines were analyzed by
      functional assays, gene expression profiling, and protein expression to identify
      the mechanism of action. RESULTS: Drug screening identified artesunate as a
      highly potent anti-lymphoma drug. Artesunate induced potent growth suppression in
      most B lymphoma cells with an IC50 comparable to concentrations measured in serum
      from artesunate-treated malaria patients, while leaving normal B-cells
      unaffected. Artesunate markedly inhibited highly aggressive tumor growth in a
      xenograft model. Gene expression analysis identified endoplasmic reticulum (ER)
      stress and the unfolded protein response as the most affected pathways and
      artesunate-induced expression of the ER stress markers ATF-4 and DDIT3 was
      specifically upregulated in malignant B-cells, but not in normal B-cells. In
      addition, artesunate significantly suppressed the overall cell metabolism,
      affecting both respiration and glycolysis. CONCLUSIONS: Artesunate demonstrated
      potent apoptosis-inducing effects across a broad range of B-cell lymphoma cell
      lines in vitro, and a prominent anti-lymphoma activity in vivo, suggesting it to
      be a relevant drug for treatment of B-cell lymphoma.

PMID- 29458390
TI  - FAK-ERK activation in cell/matrix adhesion induced by the loss of apolipoprotein
      E stimulates the malignant progression of ovarian cancer.
AB  - BACKGROUND: Extracellular matrix (ECM) is a mediator of tumor progression.
      However, whether the alterations of the intraperitoneal ECM prior to tumor
      establishment affects the malignant progression of ovarian cancer remains
      elusive. METHODS: Apolipoprotein (ApoE) knock-out mice was used to analyze the
      intraperitoneal ECM alterations by quantification of the major components of ECM.
      ID8 cells were implanted in vivo to generate allografts and human ovarian cancer
      cell lines were characterized in vitro to assess the effects of ECM alterations
      on the malignant progression of ovarian cancer. Adhesion assay, immunochemistry,
      cytokines profile, proliferation assay, transwell invasion assay and western blot
      were used to determine the malignant phenotype of ovarian cancer cells. RESULTS:
      ApoE loss induced increased ECM deposition, which stimulated the adhesions of
      ovarian cancer cells. The adhesion-mediated focal adhesion kinase (FAK) signaling
      enhanced the invasive behaviors of ovarian cancer cells through activation of a
      ERK-MMP linkage. This ECM-induced signaling cascade was further confirmed in
      human ovarian cancer cell lines in vitro. Furthermore, reversal of the ECM
      accumulation with BAPN or abrogation of adhesion-induced ERK activation in
      ovarian cancer cells with MEK inhibitors (MEKi) was found to effectively delay
      ovarian cancer progression. CONCLUSIONS: These findings identify the FAK-ERK
      activation in cell/matrix adhesion in the malignant progression of ovarian cancer
      and the efficiency of BAPN or MEKi for tumor suppression, providing an impetus
      for further studies to explore the possibility of new anticancer therapeutic
      combinations.

PMID- 29458391
TI  - Down-regulation of ghrelin receptors on dopaminergic neurons in the substantia
      nigra contributes to Parkinson's disease-like motor dysfunction.
AB  - Ghrelin exerts a wide range of physiological actions throughout the body and
      appears to be a promising target for disease therapy. Endogenous ghrelin
      receptors (GHSRs) are present in extrahypothalamic sites including the substantia
      nigra pars compacta (SNc), which is related to phenotypic dysregulation or frank
      degeneration in Parkinson's disease (PD). Here we found a dramatic decrease in
      the expression of GHSR in PD-specific induced pluripotent stem cell (iPSC)
      derived dopaminergic (DAnergic) neurons generated from patients carrying parkin
      gene (PARK2) mutations compared to those from healthy controls. Consistently, a
      significant decrease in the expression of GHSR was found in DAnergic neurons of
      isogenic PARK2-iPSC lines that mimicked loss of function of the PARK2 gene
      through CRISPR Cas9 technology. Furthermore, either intracerebroventricular
      injection or microinjection into the SNc of the selective GHSR1a antagonist [D
      Lys3]-GHRP6 in normal mice produced cataleptic behaviors related to dysfunction
      of motor coordination. These findings suggest that the down-regulation of GHSRs
      in SNc-DA neurons induced the initial dysfunction of DA neurons, leading to
      extrapyramidal disorder under PD.

PMID- 29458392
TI  - Recruitment of older adults to three preventative lifestyle improvement studies.
AB  - BACKGROUND: Recruiting isolated older adults to clinical trials is complex, time
      consuming and difficult. Previous studies have suggested querying existing
      databases to identify appropriate potential participants. We aim to compare
      recruitment techniques (general practitioner (GP) mail-outs, community engagement
      and clinician referrals) used in three randomised controlled trial (RCT) studies
      assessing the feasibility or effectiveness of two preventative interventions in
      isolated older adults (the Lifestyle Matters and Putting Life In Years
      interventions). METHODS: During the three studies (the Lifestyle Matters
      feasibility study, the Lifestyle Matters RCT, the Putting Life In Years RCT) data
      were collected about how participants were recruited. The number of letters sent
      by GP surgeries for each study was recorded. In the Lifestyle Matters RCT, we
      qualitatively interviewed participants and intervention facilitators at 6 months
      post randomisation to seek their thoughts on the recruitment process. RESULTS:
      Referrals were planned to be the main source of recruitment in the Lifestyle
      Matters feasibility study, but due to a lack of engagement from district nurses,
      community engagement was the main source of recruitment. District nurse referrals
      and community engagement were also utilised in the Lifestyle Matters and Putting
      Life In Years RCTs; both mechanisms yielded few participants. GP mail-outs were
      the main source of recruitment in both the RCTs, but of those contacted,
      recruiting yield was low (< 3%). Facilitators of the Lifestyle Matters
      intervention questioned whether the most appropriate individuals had been
      recruited. Participants recommended that direct contact with health professionals
      would be the most beneficial way to recruit. CONCLUSIONS: Recruitment to the
      Lifestyle Matters RCT did not mirror recruitment to the feasibility study of the
      same intervention. Direct district nurse referrals were not effective at
      recruiting participants. The majority of participants were recruited via GP mail
      outs, which may have led to isolated individuals not being recruited to the
      trials. Further research is required into alternative recruitment techniques,
      including respondent-driven sampling plus mechanisms which will promote health
      care professionals to recruit vulnerable populations to research. TRIAL
      REGISTRATION: International Standard Randomised Controlled Trial Registry, ID:
      ISRCTN28645428 (Putting Life In Years RCT). Registered on 11 April 2012;
      International Standard Randomised Controlled Trial Registry, ID: ISRCTN67209155
      (Lifestyle Matters RCT). Registered on 22 March 2012; ClinicalTrials.gov , ID:
      NCT03054311 (Lifestyle Matters feasibility study). Registered retrospectively on
      19 January 2017.

PMID- 29458394
TI  - Twitter use at the 2016 Conference on the Science of Dissemination and
      Implementation in Health: analyzing #DIScience16.
AB  - BACKGROUND: Poor dissemination of research findings may hamper the reach and
      impact of scientific discoveries. One key emerging platform for research
      dissemination is social media, including Twitter. While Twitter and other social
      media are increasingly being used to disseminate research content presented
      during scientific conferences, few studies have investigated the extent to which
      these tools are used throughout conferences and how they are being used. The aim
      for this study was to better understand the use of Twitter during the 2016 Annual
      Conference on the Science of Dissemination and Implementation in Health (D&I
      conference). METHODS: We performed an analysis of Twitter use before, during, and
      after the 2016 D&I conference, which took place from December 14 to 15. All
      tweets (posted between December 1 and 31) that included the conference-specific
      hashtag (#DIScience16) were assessed. We identified 2639 tweets using the data
      analytics platform NUVI. We used NUVI software to generate statistics about
      reach, influence, mentions, and origin of the tweets. Individual tweet content
      was also assessed using DiscoverText and coded for disease category,
      implementation outcomes discussed, category of tweet, and conference track.
      RESULTS: A total of 2639 tweets were analyzed; 89.1% of the tweets were posted
      during the conference. A total of 389 unique users participated on Twitter,
      representing 31 states and 22 locations outside of the USA. Most (56.8%) tweets
      were re-tweets and were used for scientific promotion (50.6%). Key conference
      speakers and implementation outcomes (de-implementation, adaptation, and
      fidelity) were commonly discussed. CONCLUSIONS: Our findings reveal that Twitter
      was used as a platform during the D&I conference, both to facilitate conference
      discussion and to promote scientific ideas. This work contributes to the existing
      data analytics and implementation science literature in two major ways: (1) by
      advancing knowledge of how social media is used during annual academic
      conferences and (2) by providing a deeper understanding of themes and emerging
      areas of interest in the dissemination and implementation sciences. Knowing
      specific topics of interest can help planners and scientists better understand
      the landscape of current and future implementation research and encourage new
      research dissemination strategies.

PMID- 29458393
TI  - Dominant integration locus drives continuous diversification of plant immune
      receptors with exogenous domain fusions.
AB  - BACKGROUND: The plant immune system is innate and encoded in the germline. Using
      it efficiently, plants are capable of recognizing a diverse range of rapidly
      evolving pathogens. A recently described phenomenon shows that plant immune
      receptors are able to recognize pathogen effectors through the acquisition of
      exogenous protein domains from other plant genes. RESULTS: We show that plant
      immune receptors with integrated domains are distributed unevenly across their
      phylogeny in grasses. Using phylogenetic analysis, we uncover a major integration
      clade, whose members underwent repeated independent integration events producing
      diverse fusions. This clade is ancestral in grasses with members often found on
      syntenic chromosomes. Analyses of these fusion events reveals that homologous
      receptors can be fused to diverse domains. Furthermore, we discover a 43 amino
      acid long motif associated with this dominant integration clade which is located
      immediately upstream of the fusion site. Sequence analysis reveals that DNA
      transposition and/or ectopic recombination are the most likely mechanisms of
      formation for nucleotide binding leucine rich repeat proteins with integrated
      domains. CONCLUSIONS: The identification of this subclass of plant immune
      receptors that is naturally adapted to new domain integration will inform
      biotechnological approaches for generating synthetic receptors with novel
      pathogen "baits."

PMID- 29458395
TI  - Herbal formula Huang Qin Ge Gen Tang enhances 5-fluorouracil antitumor activity
      through modulation of the E2F1/TS pathway.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) remains the most widely used agent to treat
      colorectal cancer (CRC). However, its clinical efficacy is currently limited by
      the development of drug resistance. Traditional Chinese Herbal Medicine (TCM) has
      been shown to enhance the efficacy of standard anticancer agents. However, there
      are only a limited number of well-controlled preclinical and clinical studies
      documenting the potential benefit of TCM. Herein, we screened a series of TCM
      formulas in in vitro and in vivo animal models to identify biologically active
      formulas that were effective against CRC. METHODS: Cell proliferation and
      clonogenic assays, cell cycle analysis, immunoblot analysis and qRT-PCR were
      performed to investigate the mechanism(s) of action of the most active formula
      Huang-Qin-Ge-Gen-Tang (HQGGT) on growth of human CRC cells. In vivo animal models
      were used to document the antitumor activity of HQGGT alone and HQGGT in
      combination with 5-FU. RESULTS: We identified HQGGT, which suppressed the in vivo
      growth of human colon cancer HT-29 xenografts without associated toxicities.
      HQGGT displayed anti-proliferative activity against a wide range of CRC cell
      lines. This growth suppression correlated with induction of apoptosis. HQGGT
      enhanced the cytotoxicity of 5-FU against human 5-FU-resistant cells (H630R1) and
      mouse colon cancer cells (MC38). Our studies showed that the mechanism of action
      of this synergism was the result of suppression of thymidylate synthase (TS)
      expression by HQGGT. We analyzed different batches of HQGGT and observed
      consistent chemical fingerprints and biological activity. Finally, we show that
      orally administered HQGGT significantly enhanced the antitumor effect of 5-FU in
      mice bearing MC38 xenografts. CONCLUSIONS: These findings provide support for the
      potential role of HQGGT as a novel modulator of fluoropyrimidine chemotherapy in
      the treatment of CRC.

PMID- 29458396
TI  - Evaluation of heat-treating heartworm-positive canine serum samples during
      treatment with Advantage Multi(r) for Dogs and doxycycline.
AB  - BACKGROUND: The use of heat-treatment in canine and feline serum has been
      hypothesized to break the formation of antigen-antibody complexes, thereby
      freeing the heartworm antigen allowing for detection by commercially available
      heartworm antigen kits. While studies have analyzed the effect of heat-treating
      serum and plasma samples in the detection of heartworm antigen, these studies
      have not utilized necropsy verified results for validation. This study evaluated
      the use of heat-treating serum samples in experimentally infected dogs during
      adulticidal treatment in comparison with necropsy adult heartworm recovery.
      METHODS: As part of a primary study, a total of 16 dogs were experimentally
      infected with 16 sexually mature adult heartworms using surgical transplantation,
      allocating 8 dogs in both the control and treated group. Treated dogs received 10
      months of topical administration of Advantage Multi(r) for Dogs (10% Imidacloprid
      + 2.5% Moxidectin) every 4 weeks and 30 days of 10 mg/kg doxycycline BID. Blood
      samples were collected from all study animals prior to surgical transplantation
      of adult heartworms, on study days 0, 1, 3, 7, 14, 21, 28, and every 4 weeks
      thereafter for the duration of this study. Concentration of heartworm antigen was
      tested using the DiroCHEK(r) heartworm antigen test kit using serum samples both
      pre- and post-heat-treatment. Serum samples were heat-treated at 103  degrees C
      in a dry heat block for 10 min and centrifuging at 1818* g for 20 min. RESULTS:
      There were a total of 4 instances (days 56, 140, 224 and 252) in 3 treated dogs
      in which a serum sample converted from negative for the detection of heartworm
      antigen prior to heat-treatment to positive for the detection of heartworm
      antigen post-heat-treatment. At necropsy, these dogs had no adult heartworms
      recovered and were all negative on antigen testing prior to and after heat
      treatment. There was 100% accuracy in the detection of either no infection, or 1
      2 adult heartworm infections using the DiroCHEK in serum samples with and without
      heat-treatment at the time of necropsy. CONCLUSIONS: The DiroCHEK accurately
      diagnosed all dogs with live adults recovered at necropsy as heartworm antigen
      positive and all those dogs with no live adults recovered at necropsy as
      heartworm antigen negative without the use of heat-treatment for samples taken on
      the day of necropsy. Therefore, these results indicate that the use of heat
      treating serum samples did not provide data of any additional value in the
      diagnosis of heartworm-positive dogs receiving treatment in this study.
      Additionally, these results may indicate that the conversion of serum samples
      from negative to positive for the presence of heartworm antigen with heat
      treatment may not always accurately diagnose live adult heartworm infections
      since no adult heartworms were recovered at necropsy for those dogs in which a
      conversion event occurred. These conversion events may be detecting residual
      antigen leftover after all adult worms have died or may even be detecting off-
      target antigens, which have been denatured during heat-treatment. While a
      necropsy was not performed at the time of the conversion events, no live adult
      worms were recovered from any of the dogs in which a conversion event occurred
      earlier in treatment.

PMID- 29458397
TI  - Human arm joints reconstruction algorithm in rehabilitation therapies assisted by
      end-effector robotic devices.
AB  - BACKGROUND: End-effector robots are commonly used in robot-assisted neuro
      rehabilitation therapies for upper limbs where the patient's hand can be easily
      attached to a splint. Nevertheless, they are not able to estimate and control the
      kinematic configuration of the upper limb during the therapy. However, the Range
      of Motion (ROM) together with the clinical assessment scales offers a
      comprehensive assessment to the therapist. Our aim is to present a robust and
      stable kinematic reconstruction algorithm to accurately measure the upper limb
      joints using only an accelerometer placed onto the upper arm. METHODS: The
      proposed algorithm is based on the inverse of the augmented Jaciobian as the
      algorithm (Papaleo, et al., Med Biol Eng Comput 53(9):815-28, 2015). However, the
      estimation of the elbow joint location is performed through the computation of
      the rotation measured by the accelerometer during the arm movement, making the
      algorithm more robust against shoulder movements. Furthermore, we present a
      method to compute the initial configuration of the upper limb necessary to start
      the integration method, a protocol to manually measure the upper arm and forearm
      lengths, and a shoulder position estimation. An optoelectronic system was used to
      test the accuracy of the proposed algorithm whilst healthy subjects were
      performing upper limb movements holding the end effector of the seven Degrees of
      Freedom (DoF) robot. In addition, the previous and the proposed algorithms were
      studied during a neuro-rehabilitation therapy assisted by the 'PUPArm' planar
      robot with three post-stroke patients. RESULTS: The proposed algorithm reports a
      Root Mean Square Error (RMSE) of 2.13cm in the elbow joint location and 1.89cm in
      the wrist joint location with high correlation. These errors lead to a RMSE about
      3.5 degrees (mean of the seven joints) with high correlation in all the joints
      with respect to the real upper limb acquired through the optoelectronic system.
      Then, the estimation of the upper limb joints through both algorithms reveal an
      instability on the previous when shoulder movement appear due to the inevitable
      trunk compensation in post-stroke patients. CONCLUSIONS: The proposed algorithm
      is able to accurately estimate the human upper limb joints during a neuro
      rehabilitation therapy assisted by end-effector robots. In addition, the
      implemented protocol can be followed in a clinical environment without
      optoelectronic systems using only one accelerometer attached in the upper arm.
      Thus, the ROM can be perfectly determined and could become an objective
      assessment parameter for a comprehensive assessment.

PMID- 29458398
TI  - Phlebotomine sand flies (Diptera: Psychodidae) in the Greek Aegean Islands:
      ecological approaches.
AB  - BACKGROUND: Blood-sucking phlebotomine sand flies are the vectors of the
      protozoan parasites Leishmania spp. Different Phlebotomus species transmit
      different Leishmania species causing leishmaniases which are neglected diseases
      emerging/reemerging in new regions. Thirteen sand fly species, ten belonging to
      the medically important genus Phlebotomus and three belonging to Sergentomyia are
      known in Greece. An increasing number of human and dog cases are reported each
      year from all parts of the country including the Aegean Islands. However, no
      previous study has been conducted on the sand fly fauna on the islands, except
      for Rhodes and Samos. The aim of this study was to investigate sand fly species
      in eleven small Aegean islands; to understand species-specific relationships with
      environmental and climatic factors and to compare sand fly community parameters
      among islands. A risk analysis was carried out for each species using climatic
      and environmental variables. RESULTS: Nine sand fly species: Phlebotomus
      neglectus, P. tobbi, P. similis, P. simici, P. perfiliewi, P. alexandri, P.
      papatasi, Sergentomyia minuta and S. dentata, were collected from the islands
      studied. Phlebotomus (Adlerius) sp. and Sergentomyia sp. specimens were also
      collected but not identified to the species level. There was a positive effect of
      distance from the sea on the abundance of P. neglectus, S. minuta and S. dentata,
      and a negative effect on the abundance of P. tobbi, P. simici and P. similis. In
      general, temperature preferences of sand fly populations were between 21 and 29 
      degrees C. Nevertheless, there were significant differences in terms of
      temperature and relative humidity preference ranges among species. The most
      important species found, P. neglectus, was indisputably the most adapted species
      in the study area with a very high reaction norm, favoring even the lower
      temperature and humidity ranges. Overall, the sand fly fauna in the islands was
      very rich but there were differences in species diversity, as indicated by the
      values of the Shannon-Wiener index, along with evenness and richness of the sand
      fly fauna between the islands and altitude ranges in the islands. CONCLUSIONS:
      The study indicated that the Greek Aegean Islands, however small, maintain a rich
      sand fly fauna. This includes important vectors of Leishmania spp. representing a
      risk for parasite transmission to humans and dogs along with the danger of
      maintaining new Leishmania spp. if introduced to the area.

PMID- 29458400
TI  - Towards an appropriate framework to facilitate responsible inclusion of pregnant
      women in drug development programs.
AB  - Evidence-based treatment for pregnant women will ultimately require research
      conducted in the population of pregnant women. Currently, few scholars have
      addressed the issue of responsible inclusion of pregnant women in drug research.
      Because of additional risks associated with including pregnant women in drug
      research and the altered ways in which drugs are processed by the pregnant body,
      pregnant women cannot be treated as an ordinary subgroup in the various phases of
      drug development. Instead, responsible inclusion of pregnant women requires
      careful design and planning of research for pregnant women specifically.
      Knowledge about these aspects is virtually nonexistent. In this article, we
      present a practical framework for the responsible inclusion of pregnant women in
      drug development. We suggest that the framework consists of using a question
      based approach with five key questions in combination with three prerequisites
      which should be addressed when considering inclusion of pregnant women in drug
      research. The five questions are: A. Can we consider the drug safe (enough) for
      first exposure in pregnant women and fetuses? B. In which dose range (potentially
      depending on gestational age) can the drug be considered to remain safe in
      pregnant women? C. At what dose (regimen, within the range considered safe) can
      we expect efficacy in pregnant women? D. Can efficacy be confirmed at the target
      dose, either similar to the initial population or different? E. Can clinical
      safety be confirmed at a sufficiently acceptable level at the target dose for
      pregnant women and fetuses, so as to conclude a positive benefit-risk ratio?
      Combining questions and prerequisites leads to a scheme for appropriate timing of
      responsible inclusion of pregnant women in drug research. Accordingly, we explore
      several research design options for including pregnant women in drug trials that
      are feasible within the framework. Ultimately, the framework may lead to (i)
      earlier inclusion of pregnant women in drug development, (ii) ensuring that key
      prerequisites, such as proper dosing, are addressed before more substantial
      numbers of pregnant women are included in trials, and (iii) optimal use of safety
      and efficacy data from the initial (nonpregnant) population throughout the drug
      development process.

PMID- 29458399
TI  - The effects of Kinesiotape on acute lateral ankle sprain: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Ankle sprains are some of the most frequent injuries of the
      musculoskeletal system. However, there is no substantive evidence supporting
      which treatment strategy is superior. Taping with Kinesiotape (KT) is a new
      method that is used as an alternative to the more established taping and bracing
      techniques used for the prophylaxis and treatment of ankle sprains. The aim of
      this study is to examine the efficacy of KT on ankle sprain by comparing
      acupuncture combined with KT (AcuKT) with acupuncture alone in patients with
      acute lateral ankle sprains. METHODS/DESIGN: This study is a prospective, multi
      center (DongShin University Gwangju Oriental Hospital, DongShin University Mokpo
      Oriental Hospital, and KyungHee Korean Medicine Hospital), outcome assessor
      blinded, randomized controlled clinical trial with a 1:1 allocation ratio.
      Participants (n = 60) with a lateral ankle sprain occurring within 1 week of the
      study will be randomly assigned to either an acupuncture group (n = 10 at each
      center (total n = 30)) or an AcuKT group (n = 10 at each center (total n = 30)).
      The acupuncture group will receive acupuncture treatment at ST36, ST41, BL60,
      BL62, KI3, KI6, GB39, and GB40 once per day, 5 days per week (excluding Saturday
      and Sunday) for 1 week. The AcuKT group will receive acupuncture treatment at
      ST36, ST41, BL60, BL62, KI3, KI6, GB39, and GB40 and the ankle meridian tendino
      musculature and a figure-of-eight shape form of KT treatment once per day, 5 days
      per week (excluding Saturday and Sunday) for 1 week. The primary outcome will be
      pain evaluation assessed according to a Visual Analogue Scale (VAS), while Foot
      and Ankle Outcome Score (FAOS), edema, European Quality of Life Five Dimension
      Five Level Scale (EQ-5D-5 L) score, and number of recurrent ankle sprains will be
      considered as secondary outcome measures. VAS, FAOS, and edema measurements will
      be performed at baseline (before intervention), 5 days after the first
      intervention (i.e., at the end of the intervention), and 4 weeks after the
      completion of intervention. EQ-5D-5 L measurements will be conducted at baseline,
      5 days after the first intervention, 4 weeks after the completion of
      intervention, and 26 weeks after the completion of intervention. The number of
      recurrent ankle sprains will be determined at 4, 8, 12, and 26 weeks after the
      completion of the intervention. DISCUSSION: This study will provide data
      regarding the efficacy of KT for the treatment of acute lateral ankle sprain. The
      results may lead to insights into the usefulness of KT in the treatment of acute
      lateral ankle sprain. TRIAL REGISTRATION: cris.nih.go.kr, ID: KCT0002257.
      Registered on 27 February 2017, and approved by the Ministry of Food and Drug
      Safety (Medical Device Clinical Trial Plan Approval #737).

PMID- 29458401
TI  - Efficacy and safety of Ding-Kun-Dan for female infertility patients with
      predicted poor ovarian response undergoing in vitro
      fertilization/intracytoplasmic sperm injection: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm
      injection (ICSI) who have a predicted poor ovarian response (POR) present a
      challenge for reproductive medicine specialists. Traditional Chinese medicine
      (TCM) is commonly used in China for such patients, in the belief that it will
      improve the ovarian response and ultimately increase pregnancy rates. However,
      there is a lack of high-quality evidence about the effect of TCM on improving
      ovarian response in such patients. The purpose of this study is to evaluate
      ongoing viable pregnancy rate at 12 weeks' gestation and related indicators of
      ovarian response in fertile women who have a predicted poor ovarian response
      having immediate versus delayed IVF/ICSI after 3 months of Ding-Kun-Dan (DKD) pre
      treatment. METHODS/DESIGN: This study is a multicenter, randomized controlled,
      parallel-group, phase III, superiority clinical trial. Two hundred and seventy
      eight eligible female infertility patients with POR will be included in the study
      and randomly allocated into an immediate treatment group and a DKD group in a 1:1
      ratio. Both groups will receive IVF or ICSI as a standard treatment while in the
      DKD group, a commercially available Chinese medicine, DKD, will be administrated
      for 3 months before the IVF/ICSI cycle starts. The primary outcome of the study
      is the ongoing pregnancy rate at 12 weeks' gestation. The secondary outcomes
      include total gonadotropin dosage, duration of stimulation, estradiol (E2) and
      progesterone (P) levels on human chorionic gonadotropin (hCG) trigger day, cycle
      cancellation rate, number of oocytes retrieved, high-quality embryo rate,
      biochemical pregnancy rate, the change of serum anti-Mullerian hormone (AMH),
      follicle-stimulating hormone (FSH), and E2 levels and all side effects, safety
      outcomes, and any adverse events. The protocol was approved by the Ethics
      Committee of the First Teaching Hospital of Tianjin university of TCM (approval
      no. TYLL2017[K] 004). DISCUSSION: IVF/ICSI is increasingly used to treat couples
      desiring a baby. Many of these women will have poor ovarian function. In China,
      DKD is commonly used for these patients prior to undergoing IVF/ICSI. There is no
      effective treatment for poor ovarian response in Western medicine currently. It
      is important, therefore, to undertake this randomized control trial to determine
      whether DKD is effective or not. TRIAL REGISTRATION: Chinese Clinical Trial
      Registry, ID: ChiCTR-IOR-17011697 . Registered on 19 June 2017.

PMID- 29458402
TI  - Management of medial humeral epicondyle fractures in children: a structured
      review protocol for a systematic review of the literature and identification of a
      core outcome set using a Delphi survey.
AB  - BACKGROUND: Medial humeral epicondyle fractures of the elbow are one of the most
      common injuries in childhood and often require surgery. There are currently no
      standardised outcome measures to assess progress after an elbow injury in a
      child. Wide variation in currently reported outcomes makes comparison of
      treatment difficult. This study aims to identify outcome measures that have
      previously been reported in studies evaluating the management of medial
      epicondyle fractures in children and to facilitate the development of a consensus
      core outcome set (COS) suitable for use in all future studies of medial humeral
      epicondyle fractures in children. METHODS/DESIGN: This study will include a
      systematic review of the academic literature to identify a list of outcome
      measures that have previously been reported. The list of outcome measures will be
      used in a consensus setting exercise with focus groups of key stakeholders to
      identify key outcomes. A Delphi process to include two rounds will then be used
      to define the most important outcomes to all stakeholders forming the COS.
      DISCUSSION: Core outcomes represent the minimum expected data reported for a
      specific condition and will improve the quality of future studies reducing bias,
      allowing easier comparison and enhancing opportunities for larger meta-analysis.
      It is anticipated that this COS will form part of the feasibility to a National
      Institute for Health Research (NIHR) Health Technology Assessment (HTA)-funded
      trial concerning the management of elbow fractures in children. TRIAL
      REGISTRATION: Core Outcome Measures in Effectiveness Trials Initiative (COMET),
      registration number: 949 . Registered on 17 January 2017. Prospero International
      prospective register of systematic reviews, registration number: CRD 42017057912
      . Registered on 16 April 2017.

PMID- 29458403
TI  - Overuse in cancer care: do European studies provide information useful to support
      policies?
AB  - Health services overuse has been acknowledged as a relevant policy issue. In this
      study, we assessed the informative value of research on the quality of cancer
      care, exploring to what extent it is actually concerned with care overuse, thus
      providing policy-makers with sound estimates of overuse prevalence. We searched
      Medline for European studies, reporting information on the rate of use of
      diagnostic or therapeutic procedures/interventions in breast, colorectal, lung
      and prostate cancer patients, published in English between 2006 and 2016.
      Individual studies were classified with regards to their orientation towards
      overuse according to the quality metrics adopted in assessing rates of use of
      procedures and interventions.Out of 1882 papers identified, 100 accounting for 94
      studies met our eligibility criteria, most of them on breast (n = 38) and
      colorectal (n = 30) cancer. Of these, 46 (49%) studies relied on process
      indicators allowing a direct measure of under- or overuse, the latter being
      addressed in 22 (24%) studies. Search for overuse in patterns of care did not
      increase over time, with overuse being measured in 24% of the studies published
      before 2010, and in only 13% of those published in 2015-2016. Information on its
      prevalence was available only for a relatively limited number of
      procedures/interventions. Overall, estimates of overuse tended to be higher for
      diagnostic procedures (median prevalence across all studies, 24%) than for drugs,
      surgical procedures or radiotherapy (median overuse prevalence always lower than
      10%). Despite its increasing policy relevance, overuse is still an often
      overlooked issue in current European research on the quality of care for cancer
      patients.

PMID- 29458404
TI  - A novel integrated care concept (NICC) versus standard care in the treatment of
      chronic cardiovascular diseases: protocol for the randomized controlled trial
      CardioCare MV.
AB  - BACKGROUND: Cardiovascular diseases are the major cause of death globally and
      represent a major economic burden on health care systems. Positive effects of
      disease management programs have been shown for patients with heart failure (HF).
      Remote monitoring and telemonitoring with active intervention are beneficial in
      atrial fibrillation (AF) and therapy-resistant hypertension (TRH), respectively.
      For these patients, we have developed a novel integrated care concept (NICC)
      which combines telemedicine with intensive support by a care center, including a
      call center, an integrated care network including inpatient and outpatient care
      providers and guideline therapy for patients. METHODS: The aim of the study is to
      demonstrate the superiority of NICC over guideline therapy alone. The trial is
      designed as open-label, bi-center, parallel-group design with two groups and a
      blinded observer. Patients will be included if they are either inpatients or if
      they are referred to the outpatient clinic of the hospitals by their treating
      physician. Randomization will be done individually with stratification by
      cardiovascular disease (AF, HF, TRH), center and admission type. Primary
      endpoints are based on the 1-year observation period after randomization. The
      first primary endpoint is the composite endpoint consisting of mortality, stroke
      and myocardial infarction. The number of hospitalizations form the second primary
      endpoint. The third primary endpoint is identical to the first primary endpoint
      plus cardiac decompensation. Adjustments for multiple testing are done using a
      fall-back strategy. Secondary endpoints include patient adherence, health care
      costs, quality of life, and safety. A sample size of 2930 gives 80% power at the
      two-sided 2.5% test level for the first primary endpoint. The power for the
      second primary endpoint is 99.8% at this sample size, and it is 80% with 1086
      patients. DISCUSSION: This study will inform care providers whether quality of
      care can be improved by an integrated care concept providing telemedicine through
      a round-the-clock call center approach. We expect that cost of the NICC will be
      lower than standard care because of reduced hospitalizations. If the study has a
      positive result, NICC is planned to be immediately rolled out in the federal
      state of Mecklenburg-West Pomerania and other federal states in Germany. The
      trial will also guide additional research to disentangle the effects of this
      complex intervention. TRIAL REGISTRATION: DRKS, ID: DRKS00013124 . Registered on
      5 October 2017; ClinicalTrials.gov , ID: NCT03317951. Registered on 17 October
      2017.

PMID- 29458405
TI  - Dacomitinib potentiates the efficacy of conventional chemotherapeutic agents via
      inhibiting the drug efflux function of ABCG2 in vitro and in vivo.
AB  - BACKGROUND: ATP-binding cassette subfamily G member 2 (ABCG2), a member of the
      ABC transporter superfamily proteins, mediates multidrug resistance (MDR) by
      transporting substrate anticancer drugs out of cancer cells and decreasing their
      intracellular accumulation. MDR is a major hurdle to successful chemotherapy. A
      logical approach to overcome MDR is to inhibit the transporter. However, no safe
      and effective MDR inhibitor has been approved in the clinic. METHODS: The MTT
      assay was used to evaluate cell cytotoxicity and MDR reversal effect. Drug efflux
      and intracellular drug accumulation were measured by flow cytometry. The
      H460/MX20 cell xenograft model was established to evaluate the enhancement of
      anticancer efficacy of topotecan by dacomitinib in vivo. To ascertain the
      interaction of dacomitinib with the substrate binding sites of ABCG2, the
      competition of dacomitinib for photolabeling of ABCG2 with [125I]-
      iodoarylazidoprazosin (IAAP) was performed. Vanadate-sensitive ATPase activity of
      ABCG2 was measured in the presence of a range of different concentrations of
      dacomitinib to evaluate the effect of dacomitinib on ATP hydrolysis as the energy
      source of the transporter. A flow cytometry-based assay and western blotting were
      employed to study whether dacomitininb could inhibit the expression level of
      ABCG2. The mRNA expression levels of ABCG2 were analyzed by real-time
      quantitative RT-PCR. The protein expression level of AKT, ERK and their
      phosphorylations were detected by Western blotting. RESULTS: Here, we found that
      dacomitinib, an irreversible pan-ErbB tyrosine kinase inhibitor (TKI) in phase
      III clinical trial, could enhance the efficacy of conventional chemotherapeutic
      agents specifically in ABCG2-overexpressing MDR cancer cells but not in the
      parental sensitive cells. Dacomitinib was found to significantly increase the
      accumulation of ABCG2 probe substrates [doxorubicin (DOX),Rhodamine 123 (Rho 123)
      and Hoechst 33342] by inhibiting the transporter efflux function. Moreover,
      dacomitinib stimulated ABCG2 ATPase activity and competed with [125I]-IAAP
      photolabeling of ABCG2 in a concentration-dependent manner. However, dacomitinib
      did not alter ABCG2 expression at protein and mRNA levels or inhibit ErbB
      downstream signaling of AKT and ERK. Importantly, dacomitinib significantly
      enhanced the efficacy of topotecan in ABCG2-overexpressing H460/MX20 cell
      xenografts in nude mice without incurring additional toxicity. CONCLUSIONS: These
      results suggest that dacomitinib reverses ABCG2-mediated MDR by inhibiting ABCG2
      efflux function and increasing intracellular accumulation of anticancer agents.
      Our findings advocate further clinical investigation of combinations of
      dacomitinib and conventional chemotherapy in cancer patients with ABCG2
      overexpressing MDR tumors.

PMID- 29458406
TI  - Assessing dengue transmission risk and a vector control intervention using
      entomological and immunological indices in Thailand: study protocol for a cluster
      randomized controlled trial.
AB  - BACKGROUND: Dengue fever is the most common and widespread mosquito-borne
      arboviral disease in the world. There is a compelling need for cost-effective
      approaches and practical tools that can reliably measure real-time dengue
      transmission dynamics that enable more accurate and useful predictions of
      incidence and outbreaks. Sensitive surveillance tools do not exist today, and
      only a small handful of new control strategies are available. Vector control
      remains at the forefront for combating dengue transmission. However, the
      effectiveness of many current vector control interventions is fraught with
      inherent weaknesses. No single vector control method is effective enough to
      control both vector populations and disease transmission. Evaluations of novel
      larval and adult control interventions are needed. METHODS/DESIGN: A cluster
      randomized controlled trial will be carried out between 2017 and 2019 in urban
      community clusters in Khon Kaen and Roi Et cities, northeastern Thailand. The
      effectiveness of a pyriproxyfen/spinosad combination treatment of permanent water
      storage containers will be evaluated on epidemiological and entomological
      outcomes, including dengue incidence, number of female adult dengue vectors
      infected or not infected with dengue virus (DENV), human exposure to Aedes
      mosquito bites, and several other indices. These indices will also be used to
      develop predictive models for dengue transmission and impending outbreaks.
      Epidemiological and entomological data will be collected continuously for 2
      years, with the intervention implemented after 1 year. DISCUSSION: The aims of
      the trial are to simultaneously evaluate the efficacy of an innovative dengue
      vector control intervention and developing predictive dengue models. Assessment
      of human exposure to mosquito bites by detecting antibodies generated against
      Aedes saliva proteins in human blood samples has, so far, not been applied in
      dengue epidemiological risk assessment and disease surveillance methodologies.
      Likewise, DENV detection in mosquitoes (adult and immature stages) has not been
      used in any practical way for routine disease surveillance strategies. The
      integration of multiple outcome measures will assist health authorities to better
      predict outbreaks for planning and applying focal and timely interventions. The
      trial outcomes will not only be important for Thailand, but also for the entire
      Southeast Asian region and further afield. TRIAL REGISTRATION: ISRCTN,
      ISRCTN73606171 . Registered on 23 June 2017.

PMID- 29458407
TI  - Effectiveness of a transdiagnostic individually tailored Internet-based and
      mobile-supported intervention for the indicated prevention of depression and
      anxiety (ICare Prevent) in Dutch college students: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Depression and anxiety are common and co-morbid disorders that affect
      a significant proportion of students. Innovative prevention strategies targeting
      both conditions are needed to reduce their health burden and costs. ICare Prevent
      is such an innovative strategy and contains a transdiagnostic individually
      tailored Internet-based and mobile-supported intervention. It addresses common
      risk factors of depression and anxiety as part of a large EU-funded multi-country
      project* (ICare). Little is known about the clinical and cost-effectiveness of
      this type of intervention compared to care as usual (CAU) for college students.
      We hypothesize that ICare Prevent will be more (cost-)effective than CAU in the
      reduction of symptoms of depression and anxiety. METHODS: A three-arm, parallel,
      randomized controlled superiority trial will be conducted comparing a guided and
      an unguided version of ICare Prevent with a control group receiving CAU. The
      trial will be open-label but outcome assessors will be blinded. A total of 252
      college students (age >= 16 years) with subclinical symptoms of depression
      defined as a score >= 16 on the Center for Epidemiological Studies Depression
      Scale (CES-D), and/or anxiety, defined as a score >= 5 on the Generalized Anxiety
      Disorder scale (GAD-7), will be included. Those meeting diagnostic criteria for a
      depressive or anxiety disorder will be excluded. The primary outcome is change in
      disorder specific symptom severity from baseline to post-intervention. Secondary
      endpoints include self-reported depression and anxiety symptoms as well as time
      to onset of a mood or anxiety disorder until 12-month follow-up. Societal costs
      and quality of life will be assessed to estimate the intervention's cost
      effectiveness compared to CAU. DISCUSSION: Transdiagnostic individually tailored
      Internet-based prevention could be a (cost-)effective approach to tackle the
      disease burden of depression and anxiety among college students. TRIAL
      REGISTRATION: Dutch trial register, NTR 6562 . Registered on 6 July 2017.

PMID- 29458408
TI  - Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing
      Persistent Atrial Fibrillation (CASA-AF): study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Atrial fibrillation is the commonest arrhythmia which raises the risk
      of heart failure, thromboembolic stroke, morbidity and death. Pharmacological
      treatments of this condition are focused on heart rate control, rhythm control
      and reduction in risk of stroke. Selective ablation of cardiac tissues resulting
      in isolation of areas causing atrial fibrillation is another treatment strategy
      which can be delivered by two minimally invasive interventions: percutaneous
      catheter ablation and thoracoscopic surgical ablation. The main purpose of this
      trial is to compare the effectiveness and safety of these two interventions.
      METHODS/DESIGN: Catheter Ablation versus Thoracoscopic Surgical Ablation in Long
      Standing Persistent Atrial Fibrillation (CASA-AF) is a prospective, multi-centre,
      randomised controlled trial within three NHS tertiary cardiovascular centres
      specialising in treatment of atrial fibrillation. Eligible adults (n = 120) with
      symptomatic, long-standing, persistent atrial fibrillation will be randomly
      allocated to either catheter ablation or thoracoscopic ablation in a 1:1 ratio.
      Pre-determined lesion sets will be delivered in each treatment arm with
      confirmation of appropriate conduction block. All patients will have an
      implantable loop recorder (ILR) inserted subcutaneously immediately following
      ablation to enable continuous heart rhythm monitoring for at least 12 months. The
      devices will be programmed to detect episodes of atrial fibrillation and atrial
      tachycardia >= 30 s in duration. The patients will be followed for 12 months,
      completing appropriate clinical assessments and questionnaires every 3 months.
      The ILR data will be wirelessly transmitted daily and evaluated every month for
      the duration of the follow-up. The primary endpoint in the study is freedom from
      atrial fibrillation and atrial tachycardia at the end of the follow-up period.
      DISCUSSION: The CASA-AF Trial is a National Institute for Health Research-funded
      study that will provide first-class evidence on the comparative efficacy, safety
      and cost-effectiveness of thoracoscopic surgical ablation and conventional
      percutaneous catheter ablation for long-standing persistent atrial fibrillation.
      In addition, the results of the trial will provide information on the effects on
      patients' quality of life. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN18250790 .
      Registered on 24 April 2015.

PMID- 29458409
TI  - Mitochondrial dysfunction and autism: comprehensive genetic analyses of children
      with autism and mtDNA deletion.
AB  - BACKGROUND: The etiology of autism spectrum disorders (ASD) is very
      heterogeneous. Mitochondrial dysfunction has been described in ASD; however,
      primary mitochondrial disease has been genetically proven in a small subset of
      patients. The main goal of the present study was to investigate correlations
      between mitochondrial DNA (mtDNA) changes and alterations of genes associated
      with mtDNA maintenance or ASD. METHODS: Sixty patients with ASD and sixty healthy
      individuals were screened for common mtDNA mutations. Next generation sequencing
      was performed on patients with major mtDNA deletions (mtdel-ASD) using two gene
      panels to investigate nuclear genes that are associated with ASD or are
      responsible for mtDNA maintenance. Cohorts of healthy controls, ASD patients
      without mtDNA alterations, and patients with mitochondrial disorders (non-ASD)
      harbouring mtDNA deletions served as comparison groups. RESULTS: MtDNA deletions
      were confirmed in 16.6% (10/60) of patients with ASD (mtdel-ASD). In 90% of this
      mtdel-ASD children we found rare SNVs in ASD-associated genes (one of those was
      pathogenic). In the intergenomic panel of this cohort one likely pathogenic
      variant was present. In patients with mitochondrial disease in genes responsible
      for mtDNA maintenance pathogenic mutations and variants of uncertain significance
      (VUS) were detected more frequently than those found in patients from the mtdel
      ASD or other comparison groups. In healthy controls and in patients without a
      mtDNA deletion, only VUS were detected in both panel. CONCLUSIONS: MtDNA
      alterations are more common in patients with ASD than in control individuals.
      MtDNA deletions are not isolated genetic alterations found in ASD; they coexist
      either with other ASD-associated genetic risk factors or with alterations in
      genes responsible for intergenomic communication. These findings indicate that
      mitochondrial dysfunction is not rare in ASD. The occurring mtDNA deletions in
      ASD may be mostly a consequence of the alterations of the causative culprit genes
      for autism or genes responsible for mtDNA maintenance, or because of the harmful
      effect of environmental factors.

PMID- 29458410
TI  - Human regulatory proteins associate with non-coding RNAs from the EBV IR1 region.
AB  - OBJECTIVE: The function of Epstein-Barr virus (EBV) stable intronic sequence
      (sis)RNAs, non-coding RNAs transcribed from a region required for EBV-mediated
      cellular transformation, remain unknown. To better understand the function of ebv
      sisRNA-1 and ebv-sisRNA-2 from the internal repeat (IR)1 region of EBV, we used a
      combination of bioinformatics and biochemistry to identify associated RNA binding
      proteins. The findings reported here are part of ongoing studies to determine the
      functions of non-coding RNAs from the IR1 region of EBV. RESULTS: Human
      regulatory proteins HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1), HNRNPC,
      HNRNPL, HuR (human antigen R), and protein LIN28A (lin-28 homolog A) were
      predicted to bind ebv-sisRNA-1 and/or ebv-sisRNA-2; FUS (fused in sarcoma) was
      predicted to associate with ebv-sisRNA-2. Protein interactions were validated
      using a combination of RNA immunoprecipitation and biotin pulldown assays. Both
      sisRNAs also precipitated with HNRNPD and NONO (non-POU domain-containing octamer
      binding protein). Interestingly, each of these interacting proteins also
      precipitated non-spliced non-coding RNA sequences transcribed from the IR1
      region. Our findings suggest interesting roles for sisRNAs (through their
      interactions with regulatory proteins) and provide further evidence for the
      existence of non-spliced stable non-coding RNAs.

PMID- 29458411
TI  - Genome-wide pleiotropy analysis of neuropathological traits related to
      Alzheimer's disease.
AB  - BACKGROUND: Simultaneous consideration of two neuropathological traits related to
      Alzheimer's disease (AD) has not been attempted in a genome-wide association
      study. METHODS: We conducted genome-wide pleiotropy analyses using association
      summary statistics from the Beecham et al. study (PLoS Genet 10:e1004606, 2014)
      for AD-related neuropathological traits, including neuritic plaque (NP),
      neurofibrillary tangle (NFT), and cerebral amyloid angiopathy (CAA). Significant
      findings were further examined by expression quantitative trait locus and
      differentially expressed gene analyses in AD vs. control brains using gene
      expression data. RESULTS: Genome-wide significant pleiotropic associations were
      observed for the joint model of NP and NFT (NP + NFT) with the single-nucleotide
      polymorphism (SNP) rs34487851 upstream of C2orf40 (alias ECRG4, P = 2.4 * 10-8)
      and for the joint model of NFT and CAA (NFT + CAA) with the HDAC9 SNP rs79524815
      (P = 1.1 * 10-8). Gene-based testing revealed study-wide significant associations
      (P <= 2.0 * 10-6) for the NFT + CAA outcome with adjacent genes TRAPPC12,
      TRAPPC12-AS1, and ADI1. Risk alleles of proxy SNPs for rs79524815 were associated
      with significantly lower expression of HDAC9 in the brain (P = 3.0 * 10-3), and
      HDAC9 was significantly downregulated in subjects with AD compared with control
      subjects in the prefrontal (P = 7.9 * 10-3) and visual (P = 5.6 * 10-4) cortices.
      CONCLUSIONS: Our findings suggest that pleiotropy analysis is a useful approach
      to identifying novel genetic associations with complex diseases and their
      endophenotypes. Functional studies are needed to determine whether ECRG4 or HDAC9
      is plausible as a therapeutic target.

PMID- 29458412
TI  - Comparison of volatile anesthetic-induced preconditioning in cardiac and cerebral
      system: molecular mechanisms and clinical aspects.
AB  - Volatile anesthetic-induced preconditioning (APC) has shown to have cardiac and
      cerebral protective properties in both pre-clinical models and clinical trials.
      Interestingly, accumulating evidences demonstrate that, except from some specific
      characters, the underlying molecular mechanisms of APC-induced protective effects
      in myocytes and neurons are very similar; they share several major intracellular
      signaling pathways, including mediating mitochondrial function, release of
      inflammatory cytokines and cell apoptosis. Among all the experimental results,
      cortical spreading depolarization is a relative newly discovered cellular
      mechanism of APC, which, however, just exists in central nervous system. Applying
      volatile anesthetic preconditioning to clinical practice seems to be a promising
      cardio-and neuroprotective strategy. In this review, we also summarized and
      discussed the results of recent clinical research of APC. Despite all the
      positive experimental evidences, large-scale, long-term, more precisely
      controlled clinical trials focusing on the perioperative use of volatile
      anesthetics for organ protection are still needed.

PMID- 29458413
TI  - Gut microbiota trajectory in early life may predict development of celiac
      disease.
AB  - BACKGROUND: To investigate whether alterations in the developing intestinal
      microbiota and immune markers precede celiac disease (CD) onset in infants at
      familial risk of developing the disease. METHODS: A nested case-control study was
      carried out as part of a larger prospective cohort study, which included healthy
      full-term newborns (> 200) with at least one first relative with biopsy-verified
      CD. The present study includes cases of CD (n = 10) and the best-matched controls
      (n = 10) who did not develop the disease after 5-year follow-up. Fecal
      microbiota, assessed by high-throughput 16S rRNA gene amplicon sequencing, and
      immune parameters were profiled at 4 and 6 months of age and related to CD onset.
      RESULTS: The microbiota of infants who remained healthy showed an increase in
      bacterial diversity over time, characterized by increases in Firmicutes families,
      but not those who developed CD. Infants who subsequently developed CD showed a
      significant reduction in sIgA levels over time, while those who remained healthy
      showed increases in TNF-alpha correlated to Bifidobacterium spp. An increased
      relative abundance of Bifidobacterium longum was associated with control children
      while increased proportions of Bifidobacterium breve and Enterococcus spp. were
      associated with CD development. CONCLUSION: The findings suggest that alterations
      in the early trajectory of gut microbiota in infants at CD risk could influence
      the immune maturation process and predispose to CD, although larger population
      studies are warranted to confirm this hypothesis.

PMID- 29458414
TI  - Bilateral internal jugular vein thrombosis due to malignant tumor.
AB  - BACKGROUND: The aim of the study was to analyze characteristics of patients with
      bilateral internal jugular vein thrombosis in our department during a 1-year
      period. Internal jugular vein thrombosis refers to an intraluminal thrombus
      occurring anywhere from the intracranial internal jugular vein to the junction of
      the internal jugular vein and the subclavian vein, which form the brachiocephalic
      vein. It can occur spontaneously or as a complication of head and neck
      infections, surgery, central venous lines, local malignancy, polycytemia,
      hyperhomocysteinemia, neck massage, or intravenous drug abuse. Spontaneous
      bilateral internal jugular vein thrombosis may occur as a result of a neoplasm, a
      condition called Trousseau's syndrome. METHODS: The medical records of four
      patients with internal jugular vein thrombosis were reviewed for patient clinical
      characteristics, including age, sex, and other diseases. This is a retrospective
      study, and we analyzed four patients who had distant malignant tumors. RESULTS:
      During a 1-year period, four male patients were referred to our department for
      bilateral internal jugular vein thrombosis. Three of them had lung neoplasm, and
      one had urinary tract neoplasm. Three patients had thrombosis in the upper arm at
      the same time, one of them in both arms. Therapy consisted of unfractioned
      heparin in all patients. The main clinical manifestations were pain and cervical
      edema. The time between the first clinical manifestation and diagnosis of
      internal jugular vein thrombosis was 4 days. In the current study, no patient
      exhibited complications due to internal jugular vein thrombosis. CONCLUSIONS:
      Diagnosing internal jugular vein thrombosis requires a high degree of suspicion.
      Our study underlines that bilateral internal jugular vein thrombosis is a risk
      indicator for malignancy. In our literature review of internal jugular vein
      thrombosis, 85% of patients exhibited unilateral thrombosis, whereas the
      remaining patients had bilateral thrombosis (15%). The knowledge of predictive
      factors of internal jugular vein thrombosis seems to be of utmost importance to
      improve patient management.

PMID- 29458415
TI  - A protocol for a systematic review of non-randomised evaluations of strategies to
      increase participant retention to randomised controlled trials.
AB  - BACKGROUND: Randomised control trials are regarded as the gold standard for
      evaluating the effectiveness and efficacy of healthcare interventions with
      thousands of trials published every year. Despite significant investment in
      infrastructure, a staggering number of clinical trials continue to face
      challenges with retention. Dropouts could lead to negative consequences-from
      lengthy delays to missing data that can undermine the results and integrity of
      the trial. Summarising evidence from non-randomised evaluations of retention
      strategies could provide complementary information to randomised evaluations that
      could guide trialists to the most effective ways of increasing retention of
      participants in clinical trials. METHODS: The following electronic databases will
      be searched for relevant studies: EMBASE, MEDLINE, the Cochrane Controlled Trials
      Register, and Cochrane Methodology Register and the search will be limited to
      English-published studies during the last 10 years to increase relevance to
      current trials. Non-randomised studies (observational studies) including a
      comparison of two or more strategies to increase participant retention in
      randomised trials or comparing one or more strategies with no strategy will be
      included. The primary outcome will be the proportion of participants remained at
      the primary analysis as determined in each retention study. DISCUSSION: This
      review aims to gather and evaluate evidence on the effect of retention strategies
      examined in non-randomised studies. It is imperative to collect evidence from
      obseravational studies to infer whether or not these studies could be considered
      a practical way to complement or even replace a broadly favourable randomised
      design. If we find that non-randomised studies to be included in this review are
      of high quality with adequate control of biases, we will recommend to trialists
      and others not to rely exclusively on randomised studies and to give meticulous
      attention to the plentiful evidence that can be obtained from non-randomised
      studies. Should the results of this review suggest that evaluating retention
      strategies in observational studies provides insufficient evidence to trialists
      planning their retention strategies, we will be able to say that there is little
      point in conducting non-randomised studies and that they would do better to
      invest their time and resources in a randomised evaluation if possible. Where a
      non-randomised study design is chosen, the review authors will offer
      recommendations to trialists and others regarding how to ensure that these
      studies are conducted in a way that can minimise the risk of bias and increase
      confidence in the findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2017:
      CRD42017072775 .

PMID- 29458416
TI  - Cholera diagnosis in human stool and detection in water: protocol for a
      systematic review of available technologies.
AB  - BACKGROUND: Cholera is a highly infectious diarrheal disease spread via fecal
      contamination of water and food sources; it is endemic in parts of Africa and
      Asia and recent outbreaks have been reported in Haiti, the Zambia and Democratic
      Republic of the Congo. If left untreated, the disease can be fatal in less than
      24 h and result in case fatality ratios of 30-50%. Cholera disproportionately
      affects those living in areas with poor access to water and sanitation: the long
      term public health response is focused on improving water and hygiene facilities
      and access. Short-term measures for infection prevention and control, and disease
      characterization and surveillance, are impaired by diagnostic delays: culture
      methods are slow and rely on the availability of infrastructure and specialist
      equipment. Rapid diagnostic tests have shown promise under field conditions and
      further innovations in this area have been proposed. METHODS: This paper is the
      protocol for a systematic review focused on identifying current technologies and
      methods used for cholera diagnosis in stool, and detection in water. We will
      synthesize and appraise information on product technical specifications, accuracy
      and design features in order to inform infection prevention and control and
      innovation development. Embase, MEDLINE, CINAHL, Proquest, IndMed and the WHO and
      Campbell libraries will be searched. We will include studies reporting on field
      evaluations, including within-study comparisons against a reference standard, and
      laboratory evaluations reporting on product validation against field stool or
      water samples. We will extract data according to protocol and attempt meta
      analyses if appropriate given data availability and quality. DISCUSSION: The
      systematic review builds on a previous scoping review in this field and expands
      upon this by synthesising data on both product technical characteristics and
      design features. The review will be of particular value to stakeholders engaged
      in diagnostic procurement and manufacturers interested in developing cholera or
      diarrheal disease diagnostics. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42016048428 .

PMID- 29458417
TI  - Cooperative p16 and p21 action protects female astrocytes from transformation.
AB  - Mechanisms underlying sex differences in cancer incidence are not defined but
      likely involve dimorphism (s) in tumor suppressor function at the cellular and
      organismal levels. As an example, sexual dimorphism in retinoblastoma protein
      (Rb) activity was shown to block transformation of female, but not male, murine
      astrocytes in which neurofibromin and p53 function was abrogated (GBM
      astrocytes). Correlated sex differences in gene expression in the murine GBM
      astrocytes were found to be highly concordant with sex differences in gene
      expression in male and female GBM patients, including in the expression of
      components of the Rb and p53 pathways. To define the basis of this phenomenon, we
      examined the functions of the cyclin dependent kinase (CDK) inhibitors, p16, p21
      and p27 in murine GBM astrocytes under conditions that promote Rb-dependent
      growth arrest. We found that upon serum deprivation or etoposide-induced DNA
      damage, female, but not male GBM astrocytes, respond with increased p16 and p21
      activity, and cell cycle arrest. In contrast, male GBM astrocytes continue to
      proliferate, accumulate chromosomal aberrations, exhibit enhanced clonogenic cell
      activity and in vivo tumorigenesis; all manifestations of broad sex differences
      in cell cycle regulation and DNA repair. Differences in tumorigenesis disappeared
      when female GBM astrocytes are also rendered null for p16 and p21. These data
      elucidate mechanisms underlying sex differences in cancer incidence and
      demonstrate sex-specific effects of cytotoxic and targeted therapeutics. This has
      critical implications for lab and clinical research.

PMID- 29458418
TI  - Amyloid beta-induced impairments on mitochondrial dynamics, hippocampal
      neurogenesis, and memory are restored by phosphodiesterase 7 inhibition.
AB  - BACKGROUND: The phosphodiesterase (PDE) 7 inhibitor S14 is a cell-permeable small
      heterocyclic molecule that is able to cross the blood-brain barrier. We
      previously found that intraperitoneal treatment with S14 exerted neuroprotection
      in an Alzheimer's disease (AD) model (in APP/PS1 mice). The objective of this
      study was to investigate the neurogenic and cellular effects of oral
      administration of S14 on amyloid beta (Abeta) overload. METHODS: We orally
      administered the PDE7 inhibitor S14 (15 mg/kg/day) or vehicle in 6-month-old
      APP/PS1 mice. After 5 weeks of S14 treatment, we evaluated cognitive functions
      and brain tissues. We also assessed the effects of S14 on the Abeta-treated human
      neuroblastome SH-SY5Y cell line. RESULTS: Targeting the cyclic adenosine
      monophosphate (cAMP)/cAMP-response element binding protein (CREB) pathway, S14
      rescued cognitive decline by improving hippocampal neurogenesis in APP/PS1
      transgenic mice. Additionally, S14 treatment reverted the Abeta-induced reduction
      in mitochondrial mass in APP/PS1 mice and in the human neuroblastoma SH-SY5Y
      cells co-exposed to Abeta. The restoration of the mitochondrial mass was found to
      be a dual effect of S14: a rescue of the mitochondrial biogenesis formerly slowed
      down by Abeta overload, and a reduction in the Abeta-increased mitochondrial
      clearance mechanism of mitophagy. CONCLUSIONS: Here, we show new therapeutic
      effects of the PDE7 inhibitor, confirming S14 as a potential therapeutic drug for
      AD.

PMID- 29458419
TI  - Insights about genome function from spatial organization of the genome.
AB  - Over the last 15 years, development of chromosome conformation capture (3C) and
      its subsequent high-throughput variants in conjunction with the fast development
      of sequencing technology has allowed investigators to generate large volumes of
      data giving insights into the spatial three-dimensional (3D) architecture of the
      genome. This huge data has been analyzed and validated using various statistical,
      mathematical, genomics, and biophysical tools in order to examine the chromosomal
      interaction patterns, understand the organization of the chromosome, and find out
      functional implications of the interactions. This review summarizes the data
      generated by several large-scale high-throughput chromosome conformation capture
      studies and the functional implications obtained from the data analyses. We also
      discuss emerging results on factors (both CCCTC binding factor (CTCF) related and
      CTCF independent) that could contribute to looping interactions.

PMID- 29458420
TI  - Effects of pharmacological and nonpharmacological treatments on brain functional
      magnetic resonance imaging in Alzheimer's disease and mild cognitive impairment:
      a critical review.
AB  - BACKGROUND: A growing number of pharmacological and nonpharmacological trials
      have been performed to test the efficacy of approved or experimental treatments
      in Alzheimer disease (AD) and mild cognitive impairment (MCI). In this context,
      functional magnetic resonance imaging (fMRI) may be a good candidate to detect
      brain changes after a short period of treatment. MAIN BODY: This critical review
      aimed to identify and discuss the available studies that have tested the efficacy
      of pharmacological and nonpharmacological treatments in AD and MCI cases using
      task-based or resting-state fMRI measures as primary outcomes. A PubMed-based
      literature search was performed with the use of the three macro-areas: 'disease',
      'type of MRI', and 'type of treatment'. Each contribution was individually
      reviewed according to the Cochrane Collaboration's tool for assessing risk of
      bias. Study limitations were systematically detected and critically discussed. We
      selected 34 pharmacological and 13 nonpharmacological articles. According to the
      Cochrane Collaboration's tool for assessing risk of bias, 40% of these studies
      were randomized but only a few described clearly the randomization procedure, 36%
      declared the blindness of participants and personnel, and only 21% reported the
      blindness of outcome assessment. In addition, 28% of the studies presented more
      than 20% drop-outs at short- and/or long-term assessments. Additional common
      shortcomings of the reviewed works were related to study design, patient
      selection, sample size, choice of outcome measures, management of drop-out cases,
      and fMRI methods. CONCLUSION: There is an urgent need to obtain efficient
      treatments for AD and MCI. fMRI is powerful enough to detect even subtle changes
      over a short period of treatment; however, the soundness of methods should be
      improved to enable meaningful data interpretation.

PMID- 29458421
TI  - Epidemiology of canine gastrointestinal helminths in sub-Saharan Africa.
AB  - BACKGROUND: Dogs have a close association with humans providing companionship,
      security and a source of dietary protein. However, dogs are also potential
      carriers of zoonotic pathogens. Dogs, therefore, pose a public health risk and a
      good understanding of canine diseases is important for planning and implementing
      control measures. The aim of this study was to characterise canine helminthiasis
      in sub-Saharan Africa using a systematic approach. METHODS: Pubmed and Google
      Scholar were searched for relevant primary studies published from 2000. Forty-one
      eligible studies were included in the meta-analysis. Pooled prevalences were
      estimated using the quality effects model. RESULTS AND CONCLUSIONS: Twenty-six
      genera of enteric helminths were reported and the pooled estimate of canine
      helminthiasis was 71% (95% CI: 63-79%). Species of Ancylostoma and Toxocara,
      causative agents of larva migrans in humans, were the most frequently reported
      helminths with pooled estimated prevalences of 41% (95% CI: 32-50%) and 22% (95%
      CI: 16-29%), respectively. Dipylidium caninum and Taenia spp. were the most
      frequently reported cestodes with pooled estimated prevalences of 20% (95% CI: 12
      29%) and 9% (95% CI: 5-15%), respectively. Trematodes were rarely reported. There
      was a high level of heterogeneity in most pooled estimates (I2 ? 80%). The
      results of this study show that canine helminthiasis is highly prevalent in sub
      Saharan Africa and there is need for regular deworming programmes to improve the
      health status of the dogs and minimise the potential health risk to humans.

PMID- 29458422
TI  - The antibiotic resistome and microbiota landscape of refugees from Syria, Iraq
      and Afghanistan in Germany.
AB  - BACKGROUND: Multidrug-resistant bacteria represent a substantial global burden
      for human health, potentially fuelled by migration waves: in 2015, 476,649
      refugees applied for asylum in Germany mostly as a result of the Syrian crisis.
      In Arabic countries, multiresistant bacteria cause significant problems for
      healthcare systems. Currently, no data exist describing antibiotic resistances in
      healthy refugees. Here, we assess the microbial landscape and presence of
      antibiotic resistance genes (ARGs) in refugees and German controls. To achieve
      this, a systematic study was conducted in 500 consecutive refugees, mainly from
      Syria, Iraq, and Afghanistan and 100 German controls. Stool samples were
      subjected to PCR-based quantification of 42 most relevant ARGs, 16S ribosomal RNA
      gene sequencing-based microbiota analysis, and culture-based validation of
      multidrug-resistant microorganisms. RESULTS: The fecal microbiota of refugees is
      substantially different from that of resident Germans. Three categories of
      resistance profiles were found: (i) ARGs independent of geographic origin of
      individuals comprising BIL/LAT/CMA, ErmB, and mefE; (ii) vanB with a high
      prevalence in Germany; and (iii) ARGs showing substantially increased prevalences
      in refugees comprising CTX-M group 1, SHV, vanC1, OXA-1, and QnrB. The majority
      of refugees carried five or more ARGs while the majority of German controls
      carried three or less ARGs, although the observed ARGs occurred independent of
      signatures of potential pathogens. CONCLUSIONS: Our results, for the first time,
      assess antibiotic resistance genes in refugees and demonstrate a substantially
      increased prevalence for most resistances compared to German controls. The
      antibiotic resistome in refugees may thus require particular attention in the
      healthcare system of host countries.

PMID- 29458423
TI  - The effectiveness of the Inspiring Futures parenting programme in improving
      behavioural and emotional outcomes in primary school children with behavioural or
      emotional difficulties: study protocol for a randomised controlled trial.
AB  - BACKGROUND: There is a need to build the evidence base of early interventions
      promoting children's health and development in the UK. Malachi Specialist Family
      Support Services ('Malachi') is a voluntary sector organisation based in the UK
      that delivers a therapeutic parenting group programme called Inspiring Futures to
      parents of children identified as having behavioural and emotional difficulties.
      The programme comprises two parts, delivered sequentially: (1) a group-based
      programme for all parents for 10-12 weeks, and (2) one-to-one sessions with
      selected parents from the group-based element for up to 12 weeks. METHODS/DESIGN:
      A randomised controlled trial will be conducted to evaluate Malachi's Inspiring
      Futures parenting programme. Participants will be allocated to one of two
      possible arms, with follow-up measures at 16 weeks (post-parent group programme)
      and at 32 weeks (post-one-to-one sessions with selected parents). The sample size
      is 248 participants with a randomisation allocation ratio of 1:1. The
      intervention arm will be offered the Inspiring Futures programme. The control
      group will receive services as usual. The aim is to determine the effectiveness
      of the Inspiring Futures programme on the primary outcome of behavioural and
      emotional difficulties of primary school children identified as having
      behavioural or emotional difficulties. DISCUSSION: This study will further
      enhance the evidence for early intervention parenting programmes for child
      behavioural and emotional problems in the UK. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN32083735 . Retrospectively registered 28 October 2014.

PMID- 29458424
TI  - Familial human prion diseases associated with prion protein mutations Y226X and
      G131V are transmissible to transgenic mice expressing human prion protein.
AB  - Human familial prion diseases are associated with mutations at 34 different prion
      protein (PrP) amino acid residues. However, it is unclear whether infectious
      prions are found in all cases. Mutant PrP itself may be neurotoxic, or
      alternatively, PrP mutation might predispose to spontaneous formation of
      infectious PrP isoforms. Previous reports demonstrated transmission to animal
      models by human brain tissue expressing 7 different PrP mutations, but 3 other
      mutations were not transmissible. In the present work, we tested transmission
      using brain homogenates from patients expressing 3 untested PrP mutants: G131V,
      Y226X, and Q227X. Human brain homogenates were injected intracerebrally into tg66
      transgenic mice overexpressing human PrP. Mice were followed for nearly 800
      days.From 593 to 762 dpi, 4 of 8 mice injected with Y226X brain had PrPSc
      detectable in brain by immunostaining, immunoblot, and PrP amyloid seeding
      activity assayed by RT-QuIC. From 531 to 784 dpi, 11 of 11 G131V-injected mice
      had PrPSc deposition in brain, but none were positive by immunoblot or RT-QuIC
      assay. In contrast, from 529 to 798 dpi, no tg66 mice injected with Q227X brain
      had PrPSc or PrP amyloid seeding activity detectable by these methods. Y226X is
      the only one of 4 known PrP truncations associated with familial disease which
      has been shown to be transmissible. This transmission of prion infectivity from a
      patient expressing truncated human PrP may have implications for the spread and
      possible transmission of other aggregated truncated proteins in prion-like
      diseases such as Alzheimer's disease, Parkinson's disease and tauopathies.

PMID- 29458425
TI  - Diffuse microvascular C5b-9 deposition is a common feature in muscle and nerve
      biopsies from diabetic patients.
AB  - Terminal complement complex deposition in endomysial capillaries detected by a
      C5b-9 immunostain is considered a diagnostic feature for dermatomyositis.
      However, we found widespread microvascular C5b-9 reactivity in a substantial
      subset of muscle biopsies with denervation changes, and in nerve biopsies of
      peripheral neuropathies, particularly in patients with diabetes. It is unclear
      whether the presence of C5b-9 deposition signifies active immune-mediated
      vascular injury that requires immune suppression therapy. We retrospectively
      identified 63 nerve biopsies in patients with a documented history of diabetes,
      26 of which had concomitant muscle biopsies, as well as 54 control nerve biopsies
      in patients without a documented diabetes history, 18 of which had concomitant
      muscle biopsies. C5b-9 immunostain was performed on all cases. 87% of the nerve
      biopsies and 92% of the muscle biopsies from diabetic patients showed
      microvascular C5b-9 reactivity, compared to 34% and 50% in non-diabetic patients.
      The differences were statistically significant (p < 0.0001 for nerve and p =
      0.002 for muscle). The C5b-9 reactivity was generally proportional to the extent
      of microvascular sclerosis in diabetic patients, but unrelated to inflammation or
      vasculitis. C5b-9 deposition in micro-vasculature in both muscle and nerve is
      therefore a common feature in patients with diabetic neuropathies and may have
      diagnostic utility. Precaution needs to be taken before using muscle capillary
      C5b-9 reactivity as evidence of myositis.

PMID- 29458426
TI  - Disease-related determinants are associated with mortality in dementia due to
      Alzheimer's disease.
AB  - BACKGROUND: Survival after dementia diagnosis varies considerably. Previous
      studies were focused mainly on factors related to demographics and comorbidity
      rather than on Alzheimer's disease (AD)-related determinants. We set out to
      answer the question whether markers with proven diagnostic value also have
      prognostic value. We aimed to identify disease-related determinants associated
      with mortality in patients with AD. METHODS: We included 616 patients (50%
      female; age 67 +/- 8 years; mean Mini Mental State Examination score 22 +/- 3)
      with dementia due to AD from the Amsterdam Dementia Cohort. Information on
      mortality was obtained from the Dutch Municipal Register. We used age- and sex
      adjusted Cox proportional hazards analysis to study associations of baseline
      demographics, comorbidity, neuropsychology, magnetic resonance imaging (MRI)
      (medial temporal lobe, global cortical and parietal atrophy, and measures of
      small vessel disease), and cerebrospinal fluid (CSF) (beta-amyloid 1-42, total
      tau, and tau phosphorylated at threonine 181 [p-tau]) with mortality (outcome).
      In addition, we built a multivariate model using forward selection. RESULTS:
      After an average of 4.9 +/- 2.0 years, 213 (35%) patients had died. Age- and sex
      adjusted Cox models showed that older age (HR 1.29 [95% CI 1.12-1.48]), male sex
      (HR 1.60 [95% CI 1.22-2.11]), worse scores on cognitive functioning (HR 1.14 [95%
      CI 1.01-1.30] to 1.31 [95% CI 1.13-1.52]), and more global and hippocampal
      atrophy on MRI (HR 1.18 [95% CI 1.01-1.37] and HR 1.18 [95% CI 1.02-1.37]) were
      associated with increased risk of mortality. There were no associations with
      comorbidity, level of activities of daily living, apolipoprotein E (APOE)
      epsilon4 status, or duration of disease. Using forward selection, the
      multivariate model included a panel of age, sex, cognitive tests, atrophy of the
      medial temporal lobe, and CSF p-tau. CONCLUSIONS: In this relatively young sample
      of patients with AD, disease-related determinants were associated with an
      increased risk of mortality, whereas neither comorbidity nor APOE genotype had
      any prognostic value.

PMID- 29458427
TI  - The genomic underpinnings of eukaryotic virus taxonomy: creating a sequence-based
      framework for family-level virus classification.
AB  - BACKGROUND: The International Committee on Taxonomy of Viruses (ICTV) classifies
      viruses into families, genera and species and provides a regulated system for
      their nomenclature that is universally used in virus descriptions. Virus
      taxonomic assignments have traditionally been based upon virus phenotypic
      properties such as host range, virion morphology and replication mechanisms,
      particularly at family level. However, gene sequence comparisons provide a
      clearer guide to their evolutionary relationships and provide the only
      information that may guide the incorporation of viruses detected in environmental
      (metagenomic) studies that lack any phenotypic data. RESULTS: The current study
      sought to determine whether the existing virus taxonomy could be reproduced by
      examination of genetic relationships through the extraction of protein-coding
      gene signatures and genome organisational features. We found large-scale
      consistency between genetic relationships and taxonomic assignments for viruses
      of all genome configurations and genome sizes. The analysis pipeline that we have
      called 'Genome Relationships Applied to Virus Taxonomy' (GRAViTy) was highly
      effective at reproducing the current assignments of viruses at family level as
      well as inter-family groupings into orders. Its ability to correctly
      differentiate assigned viruses from unassigned viruses, and classify them into
      the correct taxonomic group, was evaluated by threefold cross-validation
      technique. This predicted family membership of eukaryotic viruses with close to
      100% accuracy and specificity potentially enabling the algorithm to predict
      assignments for the vast corpus of metagenomic sequences consistently with ICTV
      taxonomy rules. In an evaluation run of GRAViTy, over one half (460/921) of
      (near)-complete genome sequences from several large published metagenomic
      eukaryotic virus datasets were assigned to 127 novel family-level groupings. If
      corroborated by other analysis methods, these would potentially more than double
      the number of eukaryotic virus families in the ICTV taxonomy. CONCLUSIONS: A
      rapid and objective means to explore metagenomic viral diversity and make
      informed recommendations for their assignments at each taxonomic layer is
      essential. GRAViTy provides one means to make rule-based assignments at family
      and order levels in a manner that preserves the integrity and underlying
      organisational principles of the current ICTV taxonomy framework. Such methods
      are increasingly required as the vast virosphere is explored.

PMID- 29458428
TI  - A review of promoting access to medicines in China - problems and
      recommendations.
AB  - BACKGROUND: Despite recent reforms, distorting funding mechanisms and over
      prescribing still maintain severe financial barriers to medicines access in
      China. Complicated and interrelated problems in the pharmaceutical sector require
      a common framework to be resolved as fragmented solutions do not work. We present
      a preliminary assessment of the impact of the national healthcare reforms on
      access to medicines, and propose policy recommendations for promoting universal
      access to medicines in China. METHODS: Drawing on multiple sources of
      information, including a review of published literatures and official national
      data, field investigations in six provinces and interviews with key opinion
      leaders, this paper presents a preliminary assessment of the impact of the
      national healthcare reforms on access to medicines, and proposes policy
      recommendations for promoting universal access to medicines in China. RESULTS:
      Public expenditure on medicines has been strictly controlled since the national
      healthcare reforms of 2009. Yet total pharmaceutical expenditure (TPE) and total
      health expenditure growth rates continuously outpaced the growth of gross
      domestic product (GDP). With 2.4% of GDP, TPE now exceeds that of most high
      income countries. The distorted provider and consumer incentives in the Chinese
      health system have not fundamentally changed. Price-setting and reimbursement
      mechanisms do not promote cost-effective use of medicines. Inappropriate price
      controls and perverse financial incentives are the un-resolved root causes of
      preference of originator brands for some major diseases and shortages of low-cost
      and low-consumption medicines. In addition, access to expensive life-saving
      medicines is yet systematically addressed. CONCLUSIONS: The complicated and
      interdependent problems interact in a way that leads to significant system
      problems in China, which create dual challenges that both the developing country
      and the developed countries are facing. To further promote access to medicines,
      China should speed up the re-assessment of the quality and efficacy of
      domestically produced generic medicines; coordinate various reforms of price
      determination, insurance payments, and procurement policies; address medicine
      shortages through comprehensive policies and legislation; establish specific
      mechanisms to achieve sustainable equitable access to expensive essential
      medicines with health technology assessment as a tool to ensure that policy and
      priority setting are created in a coherent and evidence-based way.

PMID- 29458429
TI  - Advance directives as a tool to respect patients' values and preferences:
      discussion on the case of Alzheimer's disease.
AB  - BACKGROUND: The proposal of the new criteria for the diagnosis of Alzheimer's
      disease (AD) based on biomarker data is making possible a diagnosis of AD at the
      mild cognitive impairment (MCI) or predementia/prodromal- stage. Given the
      present lack of effective treatments for AD, the opportunity for the individuals
      to personally take relevant decisions and plan for their future before and if
      cognitive deterioration occurs is one the main advantages of an early diagnosis.
      MAIN BODY: Advance directives are largely seen as an effective tool for planning
      medical care in the event the subject becomes incompetent. Nevertheless, their
      value has been questioned with regard to people with dementia by scholars who
      refer to the arguments of personal identity and of patient's changing interests
      before and after the onset of dementia. In this paper, I discuss the value of
      advance directives in Alzheimer's disease and other kind of dementia. Despite
      critics, I argue that advance directives are especially advisable in dementia and
      provide reasons in favor of their promotion at an early stage of the disease as a
      valuable tool to respect patients' values and preferences on medical treatment,
      including participation in research and end of life decisions. I mainly support
      advance directives that include both decisions regarding health care and the
      appointment of an attorney in fact. CONCLUSION: I conclude that patients with AD
      at a prodromal or early stage should be offered the opportunity to execute an
      advance directive, and that not to honor a demented individual's directive would
      be an unacceptable form of discrimination towards those patients.

PMID- 29458430
TI  - Comparison of fast multi-slice and standard segmented techniques for detection of
      late gadolinium enhancement in ischemic and non-ischemic cardiomyopathy - a
      prospective clinical cardiovascular magnetic resonance trial.
AB  - BACKGROUND: Segmented phase-sensitive inversion recovery (PSIR) cardiovascular
      magnetic resonance (CMR) sequences are reference standard for non-invasive
      evaluation of myocardial fibrosis using late gadolinium enhancement (LGE).
      Several multi-slice LGE sequences have been introduced for faster acquisition in
      patients with arrhythmia and insufficient breathhold capability. The aim of this
      study was to assess the accuracy of several multi-slice LGE sequences to detect
      and quantify myocardial fibrosis in patients with ischemic and non-ischemic
      myocardial disease. METHODS: Patients with known or suspected LGE due to chronic
      infarction, inflammatory myocardial disease and hypertrophic cardiomyopathy (HCM)
      were prospectively recruited. LGE images were acquired 10-20 min after
      administration of 0.2 mmol/kg gadolinium-based contrast agent. Three different
      LGE sequences were acquired: a segmented, single-slice/single-breath-hold fast
      low angle shot PSIR sequence (FLASH-PSIR), a multi-slice balanced steady-state
      free precession inversion recovery sequence (bSSFP-IR) and a multi-slice bSSFP
      PSIR sequence during breathhold and free breathing. Image quality was evaluated
      with a 4-point scoring system. Contrast-to-noise ratios (CNR) and acquisition
      time were evaluated. LGE was quantitatively assessed using a semi-automated
      threshold method. Differences in size of fibrosis were analyzed using Bland
      Altman analysis. RESULTS: Three hundred twelve patients were enrolled (n = 212
      chronic infarction, n = 47 inflammatory myocardial disease, n = 53 HCM) Of which
      201 patients (67,4%) had detectable LGE (n = 143 with chronic infarction, n = 27
      with inflammatory heart disease and n = 31 with HCM). Image quality and CNR were
      best on multi-slice bSSFP-PSIR. Acquisition times were significantly shorter for
      all multi-slice sequences (bSSFP-IR: 23.4 +/- 7.2 s; bSSFP-PSIR: 21.9 +/- 6.4 s)
      as compared to FLASH-PSIR (361.5 +/- 95.33 s). There was no significant
      difference of mean LGE size for all sequences in all study groups (FLASH-PSIR:
      8.96 +/- 10.64 g; bSSFP-IR: 8.69 +/- 10.75 g; bSSFP-PSIR: 9.05 +/- 10.84 g; bSSFP
      PSIR free breathing: 8.85 +/- 10.71 g, p > 0.05). LGE size was not affected by
      arrhythmia or absence of breathhold on multi-slice LGE sequences. CONCLUSIONS:
      Fast multi-slice and standard segmented LGE sequences are equivalent techniques
      for the assessment of myocardial fibrosis, independent of an ischemic or non
      ischemic etiology. Even in patients with arrhythmia and insufficient breathhold
      capability, multi-slice sequences yield excellent image quality at significantly
      reduced scan time and may be used as standard LGE approach. TRIAL REGISTRATION:
      ISRCTN48802295 (retrospectively registered).

PMID- 29458431
TI  - Construction of an organelle-like nanodevice via supramolecular self-assembly for
      robust biocatalysts.
AB  - BACKGROUND: When using the microbial cell factories for green manufacturing,
      several important issues need to be addressed such as how to maintain the
      stability of biocatalysts used in the bioprocess and how to improve the synthetic
      efficiency of the biological system. One strategy widely used during natural
      evolution is the creation of organelles which can be used for regional control.
      This kind of compartmentalization strategy has inspired the design of artificial
      organelle-like nanodevice for synthetic biology and "green chemistry". RESULTS:
      Mimicking the natural concept of functional compartments, here we show that the
      engineered thermostable ketohydroxyglutarate aldolase from Thermotoga maritima
      could be developed as a general platform for nanoreactor design via
      supramolecular self-assembly. An industrial biocatalyst-(+)-gamma-lactamase was
      selected as a model catalyst and successful encapsulated in the nanoreactor with
      high copies. These nanomaterials could easily be synthesized by Escherichia coli
      by heterologous expression and subsequently self-assembles into the target
      organelle-like nanoreactors both in vivo and in vitro. By probing their
      structural characteristics via transmission electronic microscopy and their
      catalytic activity under diverse conditions, we proved that these nanoreactors
      could confer a significant benefit to the cargo proteins. The encapsulated
      protein exhibits significantly improved stability under conditions such as in the
      presence of organic solvent or proteases, and shows better substrate tolerance
      than free enzyme. CONCLUSIONS: Our biodesign strategy provides new methods to
      develop new catalytically active protein-nanoreactors and could easily be applied
      into other biocatalysts. These artificial organelles could have widely
      application in sustainable catalysis, synthetic biology and could significantly
      improve the performance of microbial cell factories.

PMID- 29458432
TI  - Physicians' knowledge, attitudes, and perceptions concerning antibiotic
      resistance: a survey in a Ghanaian tertiary care hospital.
AB  - BACKGROUND: Understanding the knowledge, attitudes and practices of physicians
      towards antibiotic resistance is key to developing interventions aimed at
      behavior change. The survey aimed to investigate physicians' knowledge and
      attitudes towards antibiotic resistance in a tertiary-care hospital setting in
      Ghana. METHODS: We conducted a cross-sectional respondent-driven survey using a
      40-item, anonymous, voluntary, traditional paper-and-pencil self-administered
      questionnaire among 159 physicians at Korle-Bu Teaching Hospital. Single and
      multi-factor analysis were conducted to assess the study objectives. RESULTS: The
      survey was completed by 159 of 200 physicians (response rate of 79.5%). Of
      physicians, 30.1% (47/156) perceived antibiotic resistance as very important
      global problem, 18.5% (29/157) perceived it as very important national problem
      and only 8.9% (14/157) thought it as a very important problem in their hospital.
      Methicillin resistant Staphylococcus aureus was the most known about antibiotic
      resistant bacteria of public health importance followed by extended-spectrum beta
      lactamase-producing Enterobacteriaceae, carbapenem resistant Enterobacteriaceae
      (CRE) and vancomycin resistant enterococci (VRE). In multiple logistic regression
      analysis, senior physicians were nearly 3 times more likely to know about CRE
      than junior physicians. The odds of knowing about VRE increased over 4.5 times
      from being a junior to becoming senior physician. Among junior physicians, age
      had no associated effect on their knowledge of VRE or CRE. CONCLUSIONS:
      Physicians in this survey showed variable knowledge and perceptions on antibiotic
      resistance. Introducing educational programs on antibiotic resistance would be a
      useful intervention and should focus on junior physicians.

PMID- 29458433
TI  - Computational analysis identifies putative prognostic biomarkers of pathological
      scarring in skin wounds.
AB  - BACKGROUND: Pathological scarring in wounds is a prevalent clinical outcome with
      limited prognostic options. The objective of this study was to investigate
      whether cellular signaling proteins could be used as prognostic biomarkers of
      pathological scarring in traumatic skin wounds. METHODS: We used our previously
      developed and validated computational model of injury-initiated wound healing to
      simulate the time courses for platelets, 6 cell types, and 21 proteins involved
      in the inflammatory and proliferative phases of wound healing. Next, we analysed
      thousands of simulated wound-healing scenarios to identify those that resulted in
      pathological (i.e., excessive) scarring. Then, we identified candidate proteins
      that were elevated (or decreased) at the early stages of wound healing in those
      simulations and could therefore serve as predictive biomarkers of pathological
      scarring outcomes. Finally, we performed logistic regression analysis and
      calculated the area under the receiver operating characteristic curve to
      quantitatively assess the predictive accuracy of the model-identified putative
      biomarkers. RESULTS: We identified three proteins (interleukin-10, tissue
      inhibitor of matrix metalloproteinase-1, and fibronectin) whose levels were
      elevated in pathological scars as early as 2 weeks post-wounding and could
      predict a pathological scarring outcome occurring 40 days after wounding with 80%
      accuracy. CONCLUSION: Our method for predicting putative prognostic wound-outcome
      biomarkers may serve as an effective means to guide the identification of
      proteins predictive of pathological scarring.

PMID- 29458434
TI  - The German version of the Expanded Prostate Cancer Index Composite (EPIC):
      translation, validation and minimal important difference estimation.
AB  - BACKGROUND: No official German translation exists for the 50-item Expanded
      Prostate Cancer Index Composite (EPIC), and no minimal important difference (MID)
      has been established yet. The aim of the study was to translate and validate a
      German version of the EPIC with cultural adaptation to the different German
      speaking countries and to establish the MID. METHODS: We translated and
      culturally adapted the EPIC into German. For validation, we included a
      consecutive subsample of 92 patients with localized prostate cancer undergoing
      radical prostatectomy who participated the Prostate Cancer Outcomes Cohort.
      Baseline and follow-up assessments took place before and six weeks after
      prostatectomy in 2010 and 2011. We assessed the EPIC, EORTC QLQ-PR25, Feeling
      Thermometer, SF-36 and a global rating of health state change variable. We
      calculated the internal consistency, test-retest reliability, construct validity,
      responsiveness and MID. RESULTS: For most EPIC domains and subscales, our a
      priori defined criteria for reliability were fulfilled (construct reliability:
      Cronbach's alpha 0.7-0.9; test-retest reliability: intraclass-correlation
      coefficient >= 0.7). Cross-sectional and longitudinal correlations between EPIC
      and EORTC QLQ-PR25 domains ranged from 0.14-0.79, and 0.06-0.5 and 0.08-0.72 for
      Feeling Thermometer and SF-36, respectively. We established MID values of 10, 4,
      12, and 6 for the urinary, bowel, sexual and hormonal domain. CONCLUSION: The
      German version of the EPIC is reliable, responsive and valid to measure HRQL in
      prostate cancer patients and is now available in German language. With the
      suggested MID we provide interpretation to what extent changes in HRQL are
      clinically relevant for patients. Hence, study results are of interest beyond
      German speaking countries.

PMID- 29458435
TI  - Long-term effects on the progress of neuropathy after diabetic Charcot foot: an
      8.5-year prospective case-control study.
AB  - OBJECTIVE: Charcot foot is a severe complication to diabetes mellitus, associated
      with diabetic neuropathy. Any long-term effects of a Charcot foot on the progress
      of neuropathy are still largely unexplored. The objective was to investigate
      whether a previous Charcot foot had any long-term effects on the progress of
      neuropathy. RESULTS: An 8.5-year follow-up case-control study of 49 individuals
      with diabetes mellitus, 24 of whom also had Charcot foot at baseline visit in
      2005-2007. Neuropathy was assessed with a questionnaire, biothesiometry, heart
      rate variability and venous occlusion plethysmography. Of the 49 baseline
      participants, 22 were able to participate in the follow-up. Twelve had passed
      away in the meantime. Heart rate variability was unchanged in both groups; from
      9.7 to 7.2 beats/min (p = 0.053) in the Charcot group, and 14.3 to 12.6 beats/min
      (p = 0.762) in the control group. Somato-sensoric neuropathy showed no difference
      between baseline and follow-up in the Charcot group (from 39.1 to 38.5 V) (p =
      0.946), but a significantly worsened sensitivity in the control group (from 25.1
      to 38.9 V) (p = 0.002). In conclusion, we found that any differences in somatic
      or cardial autonomic neuropathy present at baseline had disappeared at follow-up
      after 8.5 years.

PMID- 29458436
TI  - Immunoregulatory functions and the therapeutic implications of GARP-TGF-beta in
      inflammation and cancer.
AB  - GARP (glycoprotein-A repetitions predominant) is a type I transmembrane cell
      surface docking receptor for latent transforming growth factor-beta (TGF-beta)
      that is abundantly expressed on regulatory T lymphocytes and platelets. GARP
      regulates the availability of membrane-bound latent TGF-beta and modulates its
      activation. For this reason, GARP expression on immune and non-immune cells is
      involved in maintaining peripheral tolerance. It plays an important role in
      preventing inflammatory diseases such as allergy and graft versus host disease
      (GvHD). GARP is also frequently hijacked by cancer cells to promote oncogenesis.
      This review summarizes the most important features of GARP biology described to
      date including gene regulation, protein expression and mechanism in activating
      latent TGF-beta, and the function of GARP in regulatory T cell biology and
      peripheral tolerance, as well as GARP's increasingly recognized roles in platelet
      mediated cancer immune evasion. The promise for GARP-targeted strategy as a novel
      immunotherapy of cancer is also highlighted.

PMID- 29458437
TI  - Ablation of caspase-1 protects against TBI-induced pyroptosis in vitro and in
      vivo.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a critical public health and
      socioeconomic problem throughout the world. Inflammation-induced secondary injury
      is one of the vital pathogenic parameters of TBI. Molecular signaling cascades of
      pyroptosis, a specific type of cellular necrosis, are key drivers of TBI-induced
      inflammation. METHODS: In this study, mice with genetically ablated caspase-1
      (caspase-1-/-) were subjected to controlled cortical impact injury in vivo, and
      primary neuron deficient in caspase-1 through siRNA knockdown and pharmacologic
      inhibition was stimulated by mechanical scratch, equiaxial stretch, and LPS/ATP
      in vitro. We evaluated the effects of caspase-1 deficiency on neurological
      deficits, inflammatory factors, histopathology, cell apoptosis, and pyroptosis.
      RESULTS: During the acute post-injury period (0-48 h) in vivo, motor deficits,
      anti-inflammatory cytokines (TGF-beta and IL-10), pro-inflammatory cytokines (IFN
      gamma, IL-1beta, and IL-18), and blood lactate dehydrogenase (LDH), as well as
      pyroptosis-related proteins (caspase-1, caspase-1 fragments, caspase-11 and
      GSDMD), were increased. Caspase-1 was activated in the cortex of TBI mice.
      Inflammatory activation was more profound in injured wild-type mice than in
      caspase-1-/- mice. In vitro, mechanical scratch, equiaxial stretch, and LPS/ATP
      induced neuron pyroptosis, apoptosis, LDH release, and increased expression of
      inflammatory factors. The effects of mechanical and inflammatory stress were
      reduced through inhibition of caspase-1 activity through siRNA knockdown and
      pharmacologic inhibition. CONCLUSION: Collectively, these data demonstrate that
      pyroptosis is involved in neuroinflammation and neuronal injury after TBI, and
      ablation of caspase-1 inhibits TBI-induced pyroptosis. Our findings suggest that
      caspase-1 may be a potential target for TBI therapy.

PMID- 29458438
TI  - Aspirin is associated with low oral pH levels and antacid helps to increase oral
      pH.
AB  - OBJECTIVE: Aspirin is a commonly used medicine for primary and secondary
      prevention of cardiovascular diseases. It is an acidic medicine associated with
      gastric irritation and acid reflux, which in turn can lead to low oral pH levels.
      Therefore, it is important to understand the association between aspirin and oral
      pH levels in order to achieve an optimum oral health condition among patients who
      take aspirin on prescription. RESULTS: Out of 373 patients, 162 (44%) were males
      and 245 (66%) were on aspirin. 71% of aspirin taking patients and 29% of non
      aspirin taking patients had oral pH less than 6.5 (P < 0.01). Aspirin showed a
      significant association with low oral pH levels (odds ratio = 1.91, 95% CI 1.23
      2.99, P < 0.01). 78 patients were given antacids and followed up for 4 weeks, 63
      of them (81%) showed an improvement in oral pH and the improvement was marked in
      the group who had oral pH between 5.5-6.0 compared to the group who had oral pH
      between 6.0-6.5 (P = 0.03). The results show that aspirin therapy is associated
      with low oral pH and administration of an antacid with aspirin helps to increase
      the oral pH level.

PMID- 29458439
TI  - Efficacy and safety assessment of a water-soluble formulation of fluralaner for
      treatment of natural Ornithonyssus sylviarum infestations in laying hens.
AB  - BACKGROUND: Northern fowl mite, Ornithonyssus sylviarum (Canestrini & Fanzago,
      1877), infestations can stress birds, impairing welfare and causing substantial
      economic losses. A study was undertaken to determine the efficacy of an
      ectoparasiticide solution (fluralaner) for oral administration in the treatment
      of mite-infested hens. METHODS: Clinically healthy, naturally mite-infested
      laying hens (n = 132), approximately 32 weeks of age, were ranked by Day -9 mite
      vent counts and randomized among 12 study pens, each to hold one of four
      treatment groups. Three groups received fluralaner-medicated water by oral gavage
      at dose rates of 0.25, 0.5 or 1.0 mg/kg on Days 0 and 7; one group was an
      untreated control (three pens for each group). Five naturally infested untreated
      birds were included in each pen to act as mite-infested source birds. Thus each
      pen, treated and control, had six non-source birds for assessment of efficacy,
      plus five source birds to provide ongoing challenge. Primary efficacy assessments
      were based on mean O. sylviarum vent counts from non-source birds in the control
      and treated group pens on Days 1, 2, 6, 8, 12, 15, 19, 22 and 26. RESULTS: Source
      birds maintained infestations throughout the study, validating the challenge to
      study birds. On Days 1 through 22, mean control group mite counts were
      significantly greater than those of the treated groups (P <= 0.013). Relative to
      the control group, mean O. sylviarum counts were reduced by at least 90% from Day
      6 through Days 19, 22 and 22 in the fluralaner 0.25, 0.5 and 1.0 mg/kg groups,
      respectively. On Day 19, mean mite counts were lower in the 0.5 and 1.0 mg/kg
      groups compared with the 0.25 mg/kg group (P <= 0.018), and in the 1.0 mg/kg
      compared with the 0.5 mg/kg group (P = 0.014). There were no adverse events in
      treated birds. CONCLUSIONS: A fluralaner solution administered twice by gavage to
      laying hens with a one-week between-treatment interval was safe and effective in
      quickly controlling O. sylviarum infestations despite continuous challenge from
      infested birds. By eliminating mites, this fluralaner solution has the potential
      to improve bird health and productivity, and to eliminate the burden of topical
      pesticide application.

PMID- 29458441
TI  - Correction to: High sensitivity troponin T and I reflect mitral annular plane
      systolic excursion being assessed by cardiac magnetic resonance imaging.
AB  - Following publication of the original article [1], the authors reported that
      there was a mistake in the Methods section -> Measurements of biomarkers (page 6,
      line 3): 2000g should read 2500g. So, the correct sentence should be "All samples
      were obtained by venipuncture into serum monovettes(r) and centrifuged at 2500g
      for 10 min at 20  degrees C."

PMID- 29458440
TI  - Agreement of self- and physician-collected samples for detection of high-risk
      human papillomavirus infections in women attending a colposcopy clinic in
      Thailand.
AB  - OBJECTIVE: To study the concordance between vaginal self- and endocervical
      physician-collected high-risk (hr) HPV testing in Thai women who attended a
      colposcopy clinic. Vaginal samples were obtained by self-sampling with a dry
      brush before endocervical samples were obtained by physicians. Both specimens
      were analyzed for hrHPV by Cobas4800 HPV test. RESULTS: Of the 247 pairs of
      samples, overall hrHPV prevalence from self- and physician-collected samples was
      41.3 and 36.0%, respectively. The overall agreement between the methods was 74.5%
      with kappa 0.46 (P < 0.001). Our study revealed moderate agreement between self-
      and physician-collected methods for hrHPV testing.

PMID- 29458442
TI  - Socio-economic differences in the change of fruit and vegetable intakes among
      Dutch adults between 2004 and 2011: the GLOBE study.
AB  - OBJECTIVE: To investigate socio-economic differences in changes in fruit and
      vegetable intake between 2004 and 2011 and explore the mediating role of
      financial barriers in this change. DESIGN: Respondents completed a self-reported
      questionnaire in 2004 and 2011, including questions on fruit and vegetable intake
      (frequency per week), indicators of socio-economic position (education, income)
      and perceived financial barriers (fruits/vegetables are expensive, financial
      distress). Associations were analysed using ordinal logistic regression. The
      mediating role of financial barriers in the association between socio-economic
      position and change in fruit and vegetable intake was studied with the Baron and
      Kenny approach. SETTING: Longitudinal GLOBE study. SUBJECTS: A total of 2978
      Dutch adults aged 25-75 years. RESULTS: Respondents with the lowest income in
      2004 were more likely to report a decrease in intake of cooked vegetables (P
      trend<0.001) and raw vegetables (P-trend<0.001) between 2004 and 2011, compared
      with those with the highest income level. Respondents with the lowest education
      level in 2004 were more likely to report a decrease in intake of fruits (P
      trend=0.021), cooked vegetables (P-trend=0.033), raw vegetables (P-trend<0.001)
      and fruit juice (P-trend=0.027) between 2004 and 2011, compared with those with
      the highest education level. Financial barriers partially mediated the
      association between income and education and the decrease in fruit and cooked
      vegetable intake between 2004 and 2011. CONCLUSIONS: These results show a
      widening of relative income and educational differences in fruit and vegetable
      intake between 2004 and 2011. Financial barriers explained a small part of this
      widening.

PMID- 29458443
TI  - Epidemiology and control measures of an OXA-48-producing Enterobacteriaceae
      hospital-wide oligoclonal outbreak.
AB  - The main objective of our study was to describe the epidemiological and
      microbiological features of an oligoclonal hospital-wide outbreak caused by OXA
      48-producing Enterobacteriaceae (OXA-48-PE). OXA-48 is a carbapenemase belonging
      to Ambler class D beta-lactamases, identified frequently in the Mediterranean and
      Southern European countries, and associated with several Enterobacteriaceae
      species. An outbreak of OXA-48-PE with a complex epidemic pattern was detected in
      January 2011. Initial control measures included contact precautions and the
      reinforcement of infection control practices, but despite all efforts made, the
      epidemiological situation hardly changed and new measures were implemented during
      2013. An observational retrospective study was performed to describe the main
      features of the outbreak and to analyse the cumulative incidence (CI) trends.
      Eight hundred and 16 patients colonised or infected by OXA-48-PE were identified
      during the 2-year period (January 2013-December 2014), female 46%, mean age
      (s.d.), 71.6 (15.2). The samples isolated in the incident cases were rectal swabs
      (80%), urine samples (10.7%), blood samples (2.8%) and other clinical samples
      (6.6%). The most frequent OXA-48-PE was Klebsiella pneumoniae. Eleven different
      clones were identified, but K. pneumoniae sequence types 11 and 405 were
      predominant: ST11 (64.2%) and ST405 (29.3%). OXA-48-PE CI trend suffered a
      statistically significant change in August 2013, which continued the following
      months. Though we could not eradicate the outbreak, we observed a statistically
      significant drop in CI after an intervention for OXA-48-PE control, based on
      patient cohort, active surveillance, electronic alerts and reinforcement of
      infection control measures in a tertiary hospital.

PMID- 29458444
TI  - Dietary energy density is positively associated with body composition of adults
      in Southwest China.
AB  - OBJECTIVE: Dietary energy density (ED) might have influences on body composition.
      We therefore examined whether ED is associated with body composition among
      Chinese adults. DESIGN: We collected dietary data through validated two-day 24 h
      recalls. ED, defined as the amount of energy per unit weight of food consumed,
      was calculated based on five methods. Multiple linear regression analyses were
      performed to explore the associations between ED and body composition parameters,
      including BMI, fat mass index (FMI), fat-free mass index (FFMI), percentage body
      fat (%BF) and waist circumference (WC). SETTING: Southwest China. SUBJECTS:
      Chinese adults (n 1933) in 2013. RESULTS: After adjusting the covariates, all ED
      definitions were positively associated with BMI, FMI, FFMI, %BF and WC among
      women (P<0.01). In men, however, ED with foods only was positively associated
      with BMI, FMI, FFMI and %BF (P<0.05), but not with WC (P=0.07); we also found
      null associations between ED with foods and all beverages and body composition
      among men. Additionally, ED contributed to higher increases of body composition
      in women than in men (P<0.01). CONCLUSIONS: The present study supports the
      positive association between ED and body composition among adults in Southwest
      China, in which beverages may play an important role.

PMID- 29458445
TI  - Using a trauma-informed policy approach to create a resilient urban food system.
AB  - OBJECTIVE: Food insecurity is associated with toxic stress and adverse long-term
      physical and mental health outcomes. It can be experienced chronically and also
      triggered or exacerbated by natural and human-made hazards that destabilize the
      food system. The Baltimore Food System Resilience Advisory Report was created to
      strengthen the resilience of the city's food system and improve short- and long
      term food security. Recognizing food insecurity as a form of trauma, the report
      was developed using the principles of trauma-informed social policy. In the
      present paper, we examine how the report applied trauma-informed principles to
      policy development, discuss the challenges and benefits of using a trauma
      informed approach, and provide recommendations for others seeking to create
      trauma-informed food policy. DESIGN: Report recommendations were developed based
      on: semi-structured interviews with food system stakeholders; input from
      community members at outreach events; a literature review; Geographic Information
      System mapping; and other analyses. The present paper explores findings from the
      stakeholder interviews. SETTING: Baltimore, Maryland, USA. SUBJECTS: Baltimore
      food system stakeholders stratified by two informant categories: organizations
      focused on promoting food access (n 13) and community leaders (n 12). RESULTS:
      Stakeholder interviews informed the recommendations included in the report and
      supported the idea that chronic and acute food insecurity are experienced as
      trauma in the Baltimore community. CONCLUSIONS: Applying a trauma-informed
      approach to the development of the Baltimore Food System Resilience Advisory
      Report contributed to policy recommendations that were community-informed and
      designed to lessen the traumatic impact of food insecurity.

PMID- 29458446
TI  - Early development and reproductive lifespan of rabbit females: implications of
      growth rate, rearing diet and body condition at first mating.
AB  - Factors influencing early development such as birth weight, nest competition, and
      the diet received during rearing have been proposed as elements conditioning the
      future reproductive performance of European rabbit (Oryctolagus cuniculus)
      females. To evaluate their effects, we followed the life of 1513 females from
      birth to time of death, culling or censoring (animals alive at a fixed date).
      Between 0 and 63 days of age 353 females died. From the remaining 1160 females,
      864 were chosen based on their birth weight to be transferred from the selection
      to the production farm. At this farm, 431 females received the control diet (184
      g of CP, 381 g of NDF and 11.8 MJ of DE per kg DM), while the other 433 received
      the fibrous diet (134 g of CP, 436 g of NDF and 10.0 MJ of DE per kg DM).
      Throughout the rearing period, we checked for the individual live weight and body
      condition (perirenal fat thickness) at first artificial insemination.
      Reproductive lifespan was defined as the number of days between the first
      parturition and the time of death, culling or censoring. Birth weight affected
      the survival of newborn females during lactation and the presence of a milk spot
      at birth (related to nest competition) increased the survivability of newborns
      weighing <45 g (P<0.001). Rearing diet altered the growth curve of females and
      their body condition at first insemination. The diet also altered the relative
      risk of death during the rearing period, which was lower among females fed on the
      fibrous diet (-12.5%; P<0.001). Therefore, a higher number of females fed with
      this diet reached their reproductive life, directly affecting the productivity
      measured per housed female. Fatter females at first insemination had smaller
      litter sizes and a higher risk of being culled than lean ones (P<0.05). In
      general, the fibrous diet reduced the risk of leaving the herd at early rearing,
      and both birth weight and perirenal fat thickness affected female's reproductive
      lifespan. An excess of fat (positive change in one unit of perirenal fat) at
      their first insemination represented an increased the risk of death or
      elimination of 13%.

PMID- 29458447
TI  - Self-monitoring of urinary salt excretion as a method of salt-reduction
      education: a parallel, randomized trial involving two groups.
AB  - OBJECTIVE: The present study aimed to evaluate salt-reduction education using a
      self-monitoring urinary salt-excretion device. DESIGN: Parallel, randomized trial
      involving two groups. The following parameters were checked at baseline and
      endline of the intervention: salt check sheet, eating behaviour questionnaire, 24
      h home urine collection, blood pressure before and after urine collection.
      SETTING: The intervention group self-monitored urine salt excretion using a self
      measuring device for 4 weeks. In the control group, urine salt excretion was
      measured, but the individuals were not informed of the result. SUBJECTS: Seventy
      eight individuals (control group, n 36; intervention group, n 42) collected two
      24 h urine samples from a target population of 123 local resident volunteers. The
      samples were then analysed. RESULTS: There were no differences in clinical
      background or related parameters between the two groups. The 24 h urinary Na:K
      ratio showed a significant decrease in the intervention group (-1.1) compared
      with the control group (-0.0; P=0.033). Blood pressure did not change in either
      group. The results of the salt check sheet did not change in the control group
      but were significantly lower in the intervention group. The score of the eating
      behaviour questionnaire did not change in the control group, but the intervention
      group showed a significant increase in eating behaviour stage. CONCLUSIONS: Self
      monitoring of urinary salt excretion helps to improve 24 h urinary Na:K, salt
      check sheet scores and stage of eating behaviour. Thus, usage of self-monitoring
      tools has an educational potential in salt intake reduction.

PMID- 29458448
TI  - Rubella antibodies in cord blood sera in Portugal: association with maternal age
      and vaccination status.
AB  - This study evaluated the impact of maternal vaccination against rubella on the
      levels of specific rubella IgG (rIgG) in 198 newborn cord sera samples. Detailed
      maternal vaccination data were available. Specific rIgG was measured using a
      commercial enzyme immunoassay. Most mothers (78.8%) had been vaccinated against
      rubella at least once in their lives. In 15 (7.6%) cord sera samples, the
      concentration of specific rIgG was below 11 IU/ml, which was classified as
      seronegative. Statistical analysis using multiple logistic regression (n = 198)
      showed that newborns of mothers born between 1986 and 1995, and those born to
      unvaccinated mothers, were more likely to be seronegative (odds ratio (ORs) 5.2
      and 4.9, respectively, adjusted for sex and gestational age). For vaccinated
      mothers (n = 156), those born between 1986 and 1995 were more likely to have
      seronegative newborns (OR 11.5 adjusting for sex, gestational age and time since
      last vaccination). Mothers of the 15 (7.6%) seronegative newborns might have been
      susceptible to rubella during pregnancy. Checking the vaccination status
      therefore recommended.

PMID- 29458449
TI  - Veterans Health Administration's Disaster Emergency Medical Personnel System
      (DEMPS) Training Evaluation: Potential Implications for Disaster Health Care
      Volunteers.
AB  - OBJECTIVE: The US Veterans Health Administration's Disaster Emergency Medical
      Personnel System (DEMPS) is a team of employee disaster response volunteers who
      provide clinical and non-clinical staffing assistance when local systems are
      overwhelmed. This study evaluated attitudes and recommendations of the DEMPS
      program to understand the impact of multi-modal training on volunteer
      perceptions. METHODS: DEMPS volunteers completed an electronic survey in 2012
      (n=2120). Three training modes were evaluated: online, field exercise, and face
      to-face. Measures included: "Training Satisfaction," "Attitudes about Training,"
      "Continued Engagement in DEMPS." Data were analyzed using chi2 and logistic
      regression. Open-ended questions were evaluated in a manner consistent with
      grounded theory methodology. RESULTS: Most respondents participated in DEMPS
      training (80%). Volunteers with multi-modal training who completed all 3 modes
      (14%) were significantly more likely to have positive attitudes about training,
      plan to continue as volunteers, and would recommend DEMPS to others (P
      value<0.001). Some respondents requested additional interactive activities and
      suggested increased availability of training may improve volunteer engagement.
      CONCLUSIONS: A blended learning environment using multi-modal training methods,
      could enhance satisfaction and attitudes and possibly encourage continued
      engagement in DEMPS or similar programs. DEMPS training program modifications in
      2015 expanded this blended learning approach through new interactive online
      learning opportunities. (Disaster Med Public Health Preparedness. 2018; page 1 of
      8).

PMID- 29458450
TI  - Transcriptomic and metabolomic responses induced in the livers of growing pigs by
      a short-term intravenous infusion of sodium butyrate.
AB  - Previous studies showed that butyrate played benefit roles in the health and
      metabolism of animals. However, little information on the effects of butyrate on
      the metabolism of piglets at the extraintestinal level is available. The present
      study investigated transcriptomic and metabolomic responses in the livers of pigs
      to evaluate the effects of intravenous sodium butyrate (SB) on the body's
      metabolism at the extraintestinal level. A total of 12 Duroc*Landrace*Large White
      growing barrows (60 days of age) fitted with jugular vein cannula were randomly
      allocated to either the SB group or the control (CO) group. Pigs in the SB group
      were intravenously infused with 10 ml SB (200 mmol/l) for 7 days, whereas pigs in
      the CO group were treated with the same amount of saline. The livers of pigs were
      collected for gene expression and metabolome analyses. The RNA sequencing (RNA
      Seq) analysis showed that the mRNA expression of Acyl-CoA synthetase long-chain
      family member 1 (ACSL1), carnitine palmitoyltransferase 1A (CPT1A), acetyl-CoA
      acyltransferase 2 (ACAA2) and phosphoenolpyruvate carboxykinase 1 (PCK1) were
      downregulated (Q<0.05), whereas fatty acid binding protein 1 (FABP1) and
      cytochrome P450 family 7 subfamily A member 1 (CYP7A1) were upregulated (P<0.05)
      by SB treatment, indicating a decrease in fatty acid oxidation and
      gluconeogenesis and an increase in fatty acid transportation and cholesterol
      metabolism. Gas chromatography-mass spectrometry analysis showed that raffinose
      was enriched in the SB group compared with the CO group, indicating a decrease in
      metabolism of galactose. Moreover, SB treatment significantly decreased the
      concentration of blood cholesterol. The results suggest that a short-term
      intravenous infusion of SB could modulate hepatic lipid metabolism by decreasing
      fatty acid oxidation and increasing fatty acid transportation and cholesterol
      metabolism.

PMID- 29458451
TI  - Increasing Perceived Emergency Preparedness by Participatory Policy-Making (Think
      Tanks).
AB  - OBJECTIVE: The study aimed to examine impact of think-tanks designed to create
      policies for emerging threats on medical teams' perceptions of individual and
      systemic emergency preparedness. METHODS: Multi-professional think-tanks were
      established to design policies for potential attacks on civilian communities. In
      total, 59 multi-sector health care managers participated in think-tanks focused
      on: (a) primary care services in risk zones; (b) hospital care; (c) casualty
      evacuation policies; (d) medical services to special-needs populations; and (e)
      services in a "temporary military-closed zone." Participants rotated
      systematically between think-tanks. Perceived individual and systemic emergency
      preparedness was reviewed pre-post participation in think-tanks. RESULTS: A
      significant increase in perceived emergency preparedness pre-post-think-tanks was
      found in 8/10 elements including in perceived individual role proficiency (3.71+/
      0.67 vs 4.60+/-0.53, respectively; P<0.001) and confidence in colleagues'
      proficiency during crisis (3.56+/-0.75 vs 4.37+/-0.61, respectively; P<0.001).
      Individual preparedness and role perception correlates with systemic preparedness
      and proficiency in risk assessment. CONCLUSIONS: Participation in policy-making
      impacts on individuals' perceptions of empowerment including trust in colleagues'
      capacities, but does not increase confidence in a system's preparedness. Field
      and managerial officials should be involved in policy-making processes, as a
      means to empower health care managers and improve interfaces and self-efficacy
      that are relevant to preparedness and response for crises. (Disaster Med Public
      Health Prepardness. 2018;page 1 of 6).

PMID- 29458452
TI  - Disaster Survivors' Anticipated Received Support in a Future Disaster.
AB  - OBJECTIVE: This study aimed to examine factors associated with receipt of post
      disaster support from network (eg, family or friends) and non-network (eg,
      government agencies) sources. METHODS: Participants (n=409) were from a
      population-based sample of Hurricane Sandy survivors surveyed 25-28 months post
      disaster. Survivors were asked to imagine a future disaster and indicate how much
      they would depend on network and non-network sources of support. In addition,
      they reported on demographic characteristics, disaster-related exposure, post
      traumatic stress, and depression. Information on the economic and social
      resources in survivors' communities was also collected. RESULTS: Multilevel
      multivariable regression models found that lack of insurance coverage and
      residence in a neighborhood wherein more persons lived alone were associated with
      survivors anticipating less network and non-network support. In addition, being
      married or cohabiting was significantly associated with more anticipated network
      support, whereas older age and having a high school education or less were
      significantly associated with less anticipated network support. CONCLUSIONS: By
      having survivors anticipate a future disaster scenario, this study provides
      insight into predictors of post-disaster receipt of network and non-network
      support. Further research is needed to examine how these findings correspond to
      survivors' received support in the aftermath of future disasters. (Disaster Med
      Public Health Preparedness. 2018;page 1 of 7).

PMID- 29458453
TI  - Consumer accounts of favourable dietary behaviour change and comparison with
      official dietary guidelines.
AB  - OBJECTIVE: The current study aimed to assess Uruguayan consumers' accounts of
      their own need to change their dietary patterns, their intended changes and the
      barriers related to doing so, and to compare the intentions and barriers with the
      recommendations of the national dietary guidelines. DESIGN: An online survey with
      2381 Uruguayan employed adults, aged between 18 and 65 years, 65 % females, was
      conducted. Participants had to answer two open-ended questions related to changes
      they could make in the foods they eat and/or the way in which they eat to improve
      the quality of their diet and the reasons why they had not implemented those
      changes yet. Content analysis using inductive coding by two researchers was used
      to analyse the responses. RESULTS: Consumers mainly intended to change
      consumption of types of foods, particularly eating more fruits, vegetables and
      legumes and consuming less flour, but also intended to alter their eating
      patterns. Lack of time and the fact that healthy foods are perceived as being
      more expensive than unhealthy foods were major barriers to behaviour change. Some
      of the recommendations of the dietary guidelines, particularly those related to
      enjoying cooking and meals and engaging in it as a social activity, were not
      represented in consumer accounts. CONCLUSIONS: Accompanying policies to the
      dietary guidelines need to underline the importance of changes in dietary
      patterns, including greater enjoyment and sharing food preparation and meals in
      the company with others, address misconceptions about flour, and provide
      concrete, consumer-derived recommendations on how to enact the guidelines.

PMID- 29458454
TI  - Setting Targets for Emergency Preparedness for a Jurisdiction's Whole Health Care
      System: The Approach Taken by New York City's Department of Health and Mental
      Hygiene.
AB  - There is little existing in the literature that provides a definition of
      readiness for a jurisdiction's whole health care system. As defining readiness at
      the system level has proven to be challenging, an approach that provides a
      framework for planning and measuring health care readiness with broad utility is
      needed. The New York City Department of Health and Mental Hygiene (DOHMH) devised
      the Readiness Target Project. Nine areas or dimensions of readiness emerged from
      this work. Through focus groups and feedback from hospital stakeholders DOHMH
      developed a matrix of readiness areas outlining current state, target state,
      gaps, and recommendations to achieve readiness. The matrix is in use as a
      systematic approach to discover and close gaps in the readiness of the whole
      health care system and to provide that system a locally valid framework to drive
      continuous improvement. This paper describes a framework for planning and
      determining the status of health care readiness at the system level for the
      jurisdiction. (Disaster Med Public Health Preparedness. 2018;page 1 of 6).

PMID- 29458455
TI  - Impact of Nepal Earthquake on Patients Presenting for Emergency Care at Patan
      Hospital.
AB  - OBJECTIVE: Natural disasters have a significant impact on the health sector. On
      April 25, 2015, Nepal was struck by a 7.8 magnitude earthquake. The aim of the
      study was to compare patient volumes and clinical conditions presenting to the
      emergency department pre- and post-earthquake. METHODS: A retrospective study was
      done at Patan Hospital Emergency Department in Kathmandu, Nepal. Volume,
      demographics, and patient diagnoses were collected for 4 months post-disaster and
      compared with cases seen the same months the year before the disaster to control
      for seasonal variations. RESULTS: After the 2015 Nepal earthquake, 12,180
      patients were seen in the emergency department. This was a significant decrease
      in patient volume compared with the 14,971 patients seen during the same months
      in 2014 (P=0.04). Of those, 5496 patients (4093 pre-disaster and 1433 post
      disaster) had a chief complaint or diagnosis recorded for analysis. An increase
      in cardiovascular and respiratory cases was seen as well as an increase in
      psychiatric cases (mostly alcohol related) and cases of anemia. There was a
      decrease in the number of obstetrics/gynecology, infectious disease, and
      poisoning cases post-earthquake. CONCLUSIONS: Understanding emergency department
      utilization after the earthquake has the potential to give further insight into
      improving disaster preparedness plans for post-disaster health needs. (Disaster
      Med Public Health Preparedness. 2018;page 1 of 6).

PMID- 29458456
TI  - Real-world use of omalizumab in patients with chronic idiopathic/spontaneous
      urticaria in the United States.
AB  - BACKGROUND: Omalizumab was approved for the treatment of chronic idiopathic
      urticaria (CIU)/chronic spontaneous urticaria (CSU) in the United States in March
      2014. OBJECTIVE: This study sought to describe real-world omalizumab use, in the
      United States, in a large cohort of patients with CIU/CSU. METHODS: Patients with
      CIU/CSU (ages >=12 years) initiated on omalizumab (index date) with >=12 months
      of pre- and postindex data were identified in the an insurance claims data base
      (January 1, 2013, to July 31, 2016). Treatment patterns, including the dosing
      regimen and continuous use of omalizumab (no gaps for >=60 days), were described
      during the 12-month postindex follow-up period. RESULTS: A total of 1546 patients
      (mean +/- standard deviation [SD] ages, 44 +/- 14.5 years; 73.1% women) were
      identified. Most of the patients (84.5%) were initiated on omalizumab 300-mg
      dose; 90% maintained the initial dose, 7.5% had a dose increase, and 4.6% had a
      dose decrease. The mean +/- SD omalizumab treatment duration was 9.1 +/- 3.8
      months, the mean +/- SD number of omalizumab administrations was 8.3 +/- 4.8, and
      the mean +/- SD administration frequency was 44 +/- 29 days. A proportion of the
      patients continuously treated with omalizumab for 6, 9, and 12 months was 67.3,
      54.8, and 47.4%, respectively. Among the patients who discontinued omalizumab for
      >=3 months (39.8%), 21% restarted the treatment after a mean +/- SD of 4.4 +/-
      1.3 months. The proportion of patients who used other CIU/CSU-related medications
      decreased pre- to postindex (94.8 to 81.1%), with the highest decrease observed
      in oral corticosteroids (75.7 to 49.9%). CONCLUSION: In this large real-world
      study, the majority of the patients with CIU/CSU were initiated on a 300-mg
      omalizumab dose and treated without titration up or down for 9 months on average.
      Most of the patients were continuously treated with omalizumab for >=6 months,
      and one-fourth of the patients who discontinued treatment resumed it. Moreover,
      compared with baseline levels, the use of other CIU/CSU-related medications was
      lower after omalizumab initiation, with the most prominent decrease observed in
      oral corticosteroids.

PMID- 29458457
TI  - Brevundimonas humi sp. nov., an alphaproteobacterium isolated from forest soil.
AB  - During a study of bacterial diversity of soil, a novel strain, CA-15T, was
      isolated from Kyonggi University forest soil. Cells were aerobic, Gram-stain
      negative, motile, non-spore-forming, rod-shaped, oxidase-positive and catalase-
      negative. Tyrosine was not oxidized but produced red pigmentation on an agar
      palte. Strain CA-15T hydrolysed Tween 60 and DNA. It grew at 15-35  degrees C
      (optimum, 25-30  degrees C), pH 6.0-10.0 (optimum, 7.0-9.0) and at 1.5 % (w/v)
      NaCl concentration. Phylogenetic analysis based on its 16S rRNA gene sequence
      indicated that strain CA-15T formed a lineage within the family Caulobacteraceae
      of the class Alphaproteobacteria that was distinct from various species of the
      genus Brevundimonas. Brevundimonas bullata DSM 7126T was the closest member of
      strain CA-15T on the basis of 16S rRNA gene sequence similarity (98.48 %). Q-10
      was only an isoprenoid quinone detected for strain CA-15T. The major polar lipids
      were 1,2-di-O-acyl-3-O-[d-glucopyranosyl-(1->4)-alphad
      glucopyranuronosyl]glycerol, 1,2-di-O-acyl-3-O-[alphad-glucopyranosyl]-sn
      glycerol, 1,2-di-O-acyl-3-O-alphad-glucopyranuronosylglycerol, 1,2-diacyl-3-O-[6'
      phosphatidyl-alphad-glucopyranosyl]glycerol and phosphatidylglycerol. The major
      cellular fatty acids were summed feature 8 (C18 : 1omega7c and/or C18 :
      1omega6c), C16 : 0, C18 : 1omega7c 11-methyl and C17 : 1omega8c. The DNA G+C
      content of strain CA-15T was 63.6 mol%. The polyphasic characterization indicated
      that strain CA-15T represents a novel species in the genus Brevundimonas, for
      which the name Brevundimonas humi sp. nov. is proposed. The type strain of
      Brevundimonas humi is CA-15T (=KEMB 9005-528T=KACC 19106T=NBRC 112677T).

PMID- 29458458
TI  - Nannocystis konarekensis sp. nov., a novel myxobacterium from an Iranian desert.
AB  - An orange-coloured myxobacterium, MNa11734T, was isolated from desert in Iran.
      MNa11734T had rod-shaped vegetative cells, moved by gliding and was
      bacteriolytic. No real fruiting body formation could be observed, but
      sporangioles were produced on water agar. The strain was mesophilic, strictly
      aerobic and chemoheterotrophic. 16S rRNA gene analyses revealed that MNa11734T
      belonged to the family Nannocystaceae, genus Nannocystis and was closely related
      to Nannocystis pusilla Na p29T (DSM 14622T) and Nannocystis exedens Na e1T (DSM
      71T), with 97.8 and 97.6 % 16S rRNA gene sequence similarity, respectively.
      Laboratory-measured DNA-DNA hybridization showed only 9.5/15.7 % (reciprocal)
      similarity between the novel strain and N. pusilla Na p29T, and 14.1/20.4 %
      between the strain and N. exedens Na e1T, whereas DNA-DNA hybridization estimates
      derived from draft genome sequences were 21.8-23.0 % and 22.2-23.7 %,
      respectively, depending on the calculation method. The G+C content of DNA from
      Nannocystis konarekensis MNa11734T was 73.3 mol%, for N. pusilla Nap29T it was
      71.8 mol% and for N. exedens Nae1T it was 72.2 mol%. The major fatty acids of the
      new strain were C16 : 1 (56.2 %), iso-C17 : 0 (14.4 %), C14 : 0 (8.2 %), C16 : 0
      (6.6 %) and iso-C15 : 0 (5.9 %). Strain MNa11734T exhibited phylogenetic and
      physiological similarities to the two other species of Nannocystis, i.e. N.
      pusilla and N. exedens, but the differences were sufficient enough to represent a
      novel species, for which the name Nannocystiskonarekensis sp. nov. is proposed.
      The type strain is MNa11734T (=DSM 104509T=NCCB 100618T).

PMID- 29458459
TI  - Tritonibacter horizontis gen. nov., sp. nov., a member of the Rhodobacteraceae,
      isolated from the Deepwater Horizon oil spill.
AB  - A heterotrophic, Gram-stain-negative, aerobic, sodium-requiring and motile
      bacterium was isolated from oil-contaminated surface water of the Gulf of Mexico
      during the Deepwater Horizon oil spill. Strain O3.65T showed highest 16S rRNA
      gene sequence similarity to Phaeobacter gallaeciensis BS107T and Phaeobacter
      inhibens T5T, both with 98.3 %, respectively. Based on complete genome analysis,
      highest similarity was observed to species of the genus Ruegeria. Strain O3.65T
      exhibited a broad salinity, temperature and pH range of 0.5-10 % NaCl, 4-45 
      degrees C and 5.5-9.0, respectively. The DNA G+C content of strain O3.65T was
      61.5 mol%. The major respiratory lipoquinone was ubiquinone-10 (Q-10), the most
      dominant fatty acids (>1 %) comprised 18 : 1omega7c and 18 : 1omega7c 11-methyl,
      10 : 0 3OH, 12 : 1 3OH, 14 : 1 3OH/3-oxo-14 : 0, 16 : 0, 16 : 0 2OH, 18 : 1 2OH
      and 12 : 1. The polar lipid pattern indicated presence of phosphatidylcholine,
      phosphatidylglycerol, an unidentified aminolipid, two unidentified phospholipids
      and seven unidentified lipids. On Difco marine broth agar, strain O3.65T formed
      smooth, shiny white to beige and convex colonies with regular edges.
      Phylogenetic, phylogenomic and phenotypic differences revealed that strain O3.65T
      represents a new species of a novel genus within the family Rhodobacteraceae, for
      which we propose the name Tritonibacter horizontis gen. nov., sp. nov. The type
      strain of the type species is O3.65T (=DSM 101689T=LMG 29740T).

PMID- 29458460
TI  - Arenibacter catalasegens sp. nov., isolated from marine surface sediment, and
      emended description of the genus Arenibacter.
AB  - A Gram-staining-negative, aerobic, non-motile, rod-shaped bacterium, designated
      as P308H10T, was isolated from surface sediment of the Southern Indian Ocean.
      Growth occurred at 4-36  degrees C (optimum 20-25  degrees C), pH 6.0-8.5
      (optimum 7.5-8.0) and in the presence of 1-8 % (w/v) NaCl (optimum 2-3 %).
      Phylogenetic analysis based on 16S rRNA gene sequences showed that strain
      P308H10T lies within the clade of members of the genus Arenibacter and is closely
      related to Arenibacterhampyeongensis HP12T (98.0 %), Arenibacterechinorum KMM
      6032T (98.4 %), Arenibacterpalladensis LMG 21972T (97.9 %),
      Arenibactertroitsensis KMM 3674T (97.9 %) and 'Arenibacter algicola' TG409 (98.1
      %). The average nucleotide identity and digital DNA-DNA hybridization values
      between strain P308H10T and the five reference strains were 85.9-80.6 % and 30.2
      23.6 %, respectively. The major fatty acids (>10 %) of strain P308H10T were
      summed feature 3, iso-C17 : 0 3-OH, iso-C15 : 1 G and iso-C15 : 0. The major
      polar lipids comprised phosphatidylethanolamine, five unidentified aminolipids
      and four unidentified lipids. The only respiratory quinone was menaquinone-6. The
      genomic DNA G+C content was 38.2 mol%. On the basis of the phenotypic,
      phylogenetic and chemotaxonomic data presented, strain P308H10T represents a
      novel species of the genus Arenibacter, for which the name Arenibacter
      catalasegens sp. nov. is proposed. The type strain is P308H10T (=GDMCC
      1.1230T=KCTC 52983T). An emended description of the genus Arenibacter is also
      proposed.

PMID- 29458461
TI  - Characterization of Desulfovibrio salinus sp. nov., a slightly halophilic sulfate
      reducing bacterium isolated from a saline lake in Tunisia.
AB  - A novel slightly halophilic sulfate-reducing bacterium, designated strain P1BSRT,
      was isolated from water of a saline lake in Tunisia. Strain P1BSRT had motile
      (single polar flagellum), Gram-negative, rod-shaped, non-spore-forming cells,
      occurring singly or in pairs. Strain P1BSRT grew at temperatures between 15 and
      45  degrees C (optimum 40  degrees C), and in a pH range between 6 and 8.5
      (optimum pH 6.7). The strain required NaCl for growth (1 % w/v), and tolerated
      high NaCl concentration (up to 12 % w/v) with an optimum of 3 % (w/v). Sulfate,
      thiosulfate and sulfite served as terminal electron acceptors, but not elemental
      sulfur, fumarate, nitrate and nitrite. Strain P1BSRT utilized lactate, pyruvate,
      formate, d-fructose and glycerol as carbon and energy sources. The main cellular
      fatty acid was C16 : 0 (50.8 %). The genomic DNA G+C content was 47.7 mol%.
      Phylogenetic analysis of 16S rRNA gene sequence similarity indicated that strain
      P1BSRT was affiliated to the genus Desulfovibrio, with the type strains
      Desulfovibrio salexigens (96.51 %), Desulfovibrio zosterae (95.68 %),
      Desulfovibrio hydrothermalis (94.81 %) and Desulfovibrio ferrireducens (94.73 %)
      as its closest phylogenetic relatives. On the basis of genotypic, phenotypic and
      phylogenetic characteristics, it is proposed to assign strain P1BSRT to a novel
      species of the genus Desulfovibrio, Desulfovibrio salinus sp. nov. The type
      strain is P1BSRT (=DSM 101510T=JCM 31065T).

PMID- 29458462
TI  - Lactobacillus panisapium sp. nov., from honeybee Apis cerana bee bread.
AB  - A novel facultatively anaerobic, Gram-stain-positive, non-motile, non-spore
      forming, catalase-negative bacterium of the genus Lactobacillus, designated
      strain Bb 2-3T, was isolated from bee bread of Apis cerana collected from a hive
      in Kunming, China. The strain was regular rod-shaped. Optimal growth occurred at
      37  degrees C, pH 6.5 with 5.0 g l-1 NaCl. The predominant fatty acids were C18 :
      1omega9c, C16 : 0 and C19 : 0 iso. Respiratory quinones were not detected. Seven
      glycolipids, three lipids, phosphatidylglycerol and diphosphatidylglycerol were
      detected. The peptidoglycan type A4alpha l-Lys-d-Asp was determined. Strain Bb 2
      3T was closely related to Lactobacillus bombicola DSM 28793T, Lactobacillus apis
      LMG 26964T and Lactobacillus helsingborgensis DSM 26265T, with 97.8, 97.6 and
      97.0 % 16S rRNA gene sequence similarity, respectively. A comparison of two
      housekeeping genes, rpoA and pheS, revealed that strain Bb 2-3T was well
      separated from the reference strains of species of the genus Lactobacillus. The
      average nucleotide identity between strain Bb 2-3T and the type strains of
      closely related species was lower than the 95-96 % threshold value for
      delineation of genomic prokaryotic species. The G+C content of the genomic DNA of
      strain Bb 2-3T was 37.4 mol%. On the basis of phenotypic, chemotaxonomic and
      phylogenetic analyses, strain Bb 2-3T is proposed to represent a novel species of
      the genus Lactobacillus, for which we propose the name Lactobacillus panisapium
      sp. nov. The type strain is Bb 2-3T (=DSM 102188T=ACCC 19955T).

PMID- 29458463
TI  - Raineya orbicola gen. nov., sp. nov. a slightly thermophilic bacterium of the
      phylum Bacteroidetes and the description of Raineyaceae fam. nov.
AB  - An isolate, designated SPSPC-11T, with an optimum growth temperature of about 50 
      degrees C and an optimum pH for growth between 7.5 and 8.0, was recovered from a
      hot spring in central Portugal. Based on phylogenetic analysis of its 16S rRNA
      sequence, the new organism is most closely related to the species of the genus
      Thermonema but with a pairwise sequence similarity of <85 %. The isolate was
      orange-pigmented, formed non-motile long filaments and rod-shaped cells that
      stain Gram-negative. The organism was strictly aerobic, oxidase-positive and
      catalase-positive. The major fatty acids were iso-C15:0, iso-C15 : 0 2-OH and iso
      C17 : 0 3-OH. The major polar lipids were one aminophospholipid, two aminolipids
      and three unidentified lipids. Menaquinone 7 was the major respiratory quinone.
      The DNA G+C content of strain SPSPC-11T was 37.6 mol% (draft genome sequence).
      The high quality draft genome sequence corroborated many of the phenotypic
      characteristics of strain SPSPC-11T. Based on genotypic, phylogenetic,
      physiological and biochemical characterization we describe a new species of a
      novel genus represented by strain SPSPC-11T (=CECT 9012T=LMG 29233T) for which we
      propose the name Raineya orbicola gen. nov., sp. nov. We also describe the family
      Raineyaceae to accommodate this new genus and species.

PMID- 29458464
TI  - Delineation of a novel subgroup 16SrXIII-J phytoplasma, a 'Candidatus Phytoplasma
      hispanicum'-related strain, based on computer-simulated RFLP and phylogenetic
      analysis.
AB  - Symptoms of fruit phyllody and slow growth, which are suggestive of phytoplasma
      infection, were observed in strawberry plants cultivated in commercial fields. In
      order to provide evidence of association of phytoplasma with affected plants,
      assays for detecting and identifying were performed through computer-simulated
      restriction fragment length polymorphism (RFLP) and phylogenetic analysis. Total
      DNA was extracted from symptomatic and asymptomatic samples and used as template
      in nested PCR primed by the primers P1/Tint followed by R16F2n/16R2. Amplified
      DNA fragments of 1.2 kb from the 16S rRNA gene revealed the presence of
      phytoplasma in all symptomatic samples. Molecular detection was confirmed by
      electron transmission microscopy, which evidenced pleomorphic bodies in the
      phloem vessels. Nucleotide sequence representative of the strawberry phytoplasma
      shared 97.2 to 99 % similarity with phytoplasmas currently classified as members
      of the distinct subgroups within the 16SrXIII group. Similarity coefficient (F)
      values ranged from 0.70 to 0.92, indicating that strawberry phytoplasma
      delineates a new strain in addition to 'Candidatus Phytoplasma hispanicum'
      related strains. The evolutionary tree displayed that this strain emerges as a
      new branch in relation to those previously described. The novel strain,
      designated SFP (strawberry fruit phyllody) phytoplasma represents the new
      16SrXIII-J subgroup and its sequence, denominated SFP-Br02, was deposited in the
      GenBank database (EU719108). These findings contribute for the knowledge of the
      genetic diversity existing among members of the group 16SrXIII and establishes
      strawberry as an additional host of representatives of this group in Brazil.

PMID- 29458465
TI  - Xylanibacillus composti gen. nov., sp. nov., isolated from compost.
AB  - A novel Gram-stain-positive bacterial strain, designated as K13T, was isolated
      from compost and characterized using a polyphasic approach to determine its
      taxonomic position. On the basis of 16S rRNA gene sequence analysis, the strain
      showed highest similarity (93.8 %) to Paenibacillus nanensis MX2-3T. Cells of
      strain K13T were aerobic, motile rods. The major fatty acids were anteiso C15 : 0
      (34.4 %), iso C16 : 0 (17.3 %) and C16 : 0 (10.0 %). The major menaquinone was MK
      7, the polar lipid profile included diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine and an
      aminophospholipid. The DNA G+C content was 52.3 %. Based on phenotypic, including
      chemotaxonomic characteristics and analysis of the 16S rRNA gene sequences, it
      was concluded that strain K13T represents a novel genus, for which the name
      Xylanibacillus gen. nov., sp. nov. is proposed. The type species of the genus is
      Xylanibacillus composti, the type strain of which is strain K13T (=DSM
      29793T=NCAIM B.02605T).

PMID- 29458466
TI  - Deinococcus aluminii sp. nov., isolated from an automobile air conditioning
      system.
AB  - A Gram-stain-positive and pale pink-pigmented bacterial strain, designated
      ID0501T, was isolated from an automobile evaporator core collected in the
      Republic of Korea. The cells were aerobic and coccoidal. The strain grew at 15-40
      C (optimum, 37 C), at pH 6.0-7.0 (optimum, pH 6.5), and in the presence of 0-1.5
      % (w/v) NaCl. Phylogenetically, the strain was related to members of the genus
      Deinococcus and showed the highest sequence similarity, of 96.9 %, with
      Deinococcus metallilatus MA1002T. The major fatty acids of the strain were iso
      C17 : 0, iso-C15 : 0 and iso-C13 : 0. The predominant respiratory quinone was MK
      8. The polar lipids profile revealed the presence of phosphatidylethanolamine,
      phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, unidentified
      phospholipids, an unidentified aminolipid and unidentified glycolipids. The DNA
      G+C content of the strain was 68.3 mol%. On the basis of phenotypic, genotypic
      and chemotaxonomic data, strain ID0501T represents a novel species of the genus
      Deinococcus, for which the name Deinococcusaluminii sp. nov. (=KACC 19286T=NBRC
      112889T) is proposed.

PMID- 29458467
TI  - Chitinophaga humicola sp. nov., isolated from oil-contaminated soil.
AB  - A yellow-coloured, Gram-stain-negative, non-motile, aerobic and rod-shaped
      bacterium, designated strain Ktm-2T, was isolated from oil-contaminated soil.
      Strain Ktm-2T was able to grow at 15 to 40  degrees C, pH 4.5-10.0 and 0-2 %
      (w/v) NaCl concentration. This strain was taxonomically characterized by a
      polyphasic approach. Based on the 16S rRNA gene sequence analysis, strain Ktm-2T
      represented a member of the genus Chitinophaga and shared highest sequence
      similarity with Chitinophaga barathri YLT18T (98.1 %), Chitinophaga cymbidii R156
      2T (96.4 %) and Chitinophaga niabensis JS13-10T (96.3 %). The only respiratory
      quinone was menaqunone-7, the major polar lipid was phosphatidylethanolamine and
      the predominant fatty acids were iso-C15 : 0, C16 : 1omega5c and iso-C17 : 0 3
      OH. The DNA G+C content was 52.1 mol%. The DNA-DNA relatedness between strain Ktm
      2T and C. barathri YLT18T was 22.0 %, which falls below the threshold value of 70
      % for the strain to be considered a novel species. The morphological,
      physiological, chemotaxonomic and phylogenetic analyses clearly distinguished
      this strain from its closest phylogenetic neighbours. Thus, strain Ktm-2T
      represents a novel species of the genus Chitinophaga, for which the name
      Chitinophagahumicola sp. nov. is proposed. The type strain is Ktm-2T (=KEMB 9005
      693T=KACC 19388T=JCM 32158T).

PMID- 29458468
TI  - Aquimarina spongiicola sp. nov., isolated from spongin.
AB  - A Gram-reaction-negative, aerobic, motile by gliding, non-spore-forming, rod
      shaped bacterial strain, designated 122CH820-2T, was isolated from spongin. This
      bacterium was characterized to determine its taxonomic position by using a
      polyphasic approach. Strain 122CH820-2T grew well at 25-30  degrees C on marine
      agar. On the basis of 16S rRNA gene sequence similarity, strain 122CH820-2T
      belonged to the family Flavobacteriaceae and was closely related to Aquimarina
      mytili PSC33T (96.8 % sequence similarity) and A. penaei P3-1T (96.7 %). Lower
      sequence similarities (<96.5 %) were found with all of the other recognized
      members of the genus Aquimarina. The G+C content of the genomic DNA was 35.2
      mol%. The major respiratory quinone was menaquinone MK-6 and the major fatty
      acids were C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 1 G and iso-C15 : 0 3-OH. The
      polar lipids were phosphatidylethanolamine, one aminophospholipid and five
      unidentified polar lipids. Strain 122CH820-2T could be differentiated
      genotypically and phenotypically from recognized species of the genus Aquimarina.
      The isolate therefore represents a novel species, for which the name Aquimarina
      spongiicola sp. nov. is proposed, with the type strain 122CH820-2T (=KACC
      19274T=LMG 30078T).

PMID- 29458469
TI  - Sandarakinorhabdus cyanobacteriorum sp. nov., a novel bacterium isolated from
      cyanobacterial aggregates in a eutrophic lake.
AB  - A bacterial strain, designated TH057T, was isolated from cyanobacterial
      aggregates in a eutrophic lake in China. Cells were observed to be slightly
      curved, rod-shaped, capsule-forming and stained Gram-negative. Optimal growth was
      obtained at pH 7.0 (range: pH 5-9) and 30  degrees C (range: 20-37  degrees C) in
      R2A broth. According to the absorption spectrum, carotenoids (455 and 490 nm) and
      light-harvesting complex LHI (857 nm) were present in the cells. The cells were
      found to be positive for oxidase and catalase activities. The major respiratory
      quinone was ubiquinone Q-10. The major fatty acids were identified as C17 :
      1omega6c, C16 : 1omega7c/C16 : 1omega6c, C18 : 1omega6c/C18 : 1omega7c and C16 :
      0. The major polar lipids were found to consist of phosphatidylethanolamine,
      diphosphatidylglycerol, phosphatidylglycerol, unidentified glycolipid and two
      sphingoglycolipids. Strain TH057T shared highest 16S rRNA gene sequence
      similarity to Sandarakinorhabdus limnophila so42T (96.8 %), followed by
      Polymorphobacter fuscus D40PT (95.8 %). The genomic G+C content of strain TH057T
      was 66.1 mol% based on total genome calculations. The average nucleotide identity
      and the digital DNA-DNA hybridization value for the complete genomes were 81.0
      and 23.0 % between strain TH057T and Sandarakinorhabdus limnophila so42T. The
      phenotypic, chemotaxonomic and phylogenetic properties, and genome analysis
      suggested that strain TH057T represents a novel species within the genus
      Sandarakinorhabdus, for which the name Sandarakinorhabduscyanobacteriorum sp.
      nov. is proposed. The type strain is TH057T (=CGMCC 1.15803T=LMG 30294T).

PMID- 29458470
TI  - Flavobacterium ovatum sp. nov., a marine bacterium isolated from an Antarctic
      intertidal sandy beach.
AB  - A rod-shaped, Gram-staining-negative, strictly aerobic, non-motile bacterium with
      no flexirubin-type pigment, designated as W201ET, was isolated from an intertidal
      sandy beach in Antarctica. The organism formed faintly yellow, round colonies on
      marine agar 2216E. The strain required sea salts for growth and grew optimally in
      the presence of 2 % (w/v) NaCl at pH 7.0, 20  degrees C. Phylogenetic analysis
      based on 16S rRNA gene sequence indicated that strain W201ET belonged to the
      genus Flavobacterium and showed the highest sequence similarity to Flavobacterium
      algicola NBRC 102673T (96.5 %). The major respiratory quinone was menaquinone 6,
      and the predominant fatty acids were iso-C15 : 1 G, iso-C15 : 0, iso-C15 : 0 3-OH
      and summed feature 3 (which comprises C16 : 1omega7c and/or C16 : 1omega6c). The
      polar lipids of strain W201ET comprised one phosphatidylethanolamine, two
      unidentified aminolipids and three unidentified polar lipids. The DNA G+C content
      of strain W201ET was 34.1 mol%. On the basis of the polyphasic analyses, this
      isolate was considered to represent a novel species in the genus Flavobacterium,
      for which the name Flavobacterium ovatum sp. nov. is proposed. The type strain is
      W201ET (=KCTC 52693T=MCCC 1K03251T=CGMCC 1.16053T).

PMID- 29458471
TI  - Proposal of Litorimonas haliclonae sp. nov., isolated from a marine sponge of the
      genus Haliclona.
AB  - A bright-orange-pigmented, Gram-stain-negative, motile, and rod-shaped bacterium,
      strain MAA42T, was isolated from a marine sponge of the genus Haliclona, which is
      in long-time culture in a marine aquarium system at the Justus Liebig University
      Giessen, Germany. The strain grew at 4-34  degrees C (optimum 28  degrees C), in
      the presence of 0.5-9.5 % (w/v) NaCl (optimum 3.5 %) and at pH 4.5-10.0 (optimum
      pH 7.5). Strain MAA42T shared the highest 16S rRNA gene sequence similarity (98.1
      %) with the type strain of Litorimonas taeanensis. Sequence similarities to all
      other closely related type strains were below 97 %. DNA-DNA hybridization of
      strain MAA42T with L. taeanensis DSM 22008T resulted in values of 4.7 %
      (reciprocal 17.7 %). Major cellular fatty acids of strain MAA42T were C18 :
      1omega7c (66.2 %), C18 : 1 2-OH (17.4 %), and C18 : 0 (14.1 %). Spermidine was
      predominant in the polyamine pattern, and ubiquinone Q-10 was the major
      respiratory quinone. The polar lipid profile contained the major compounds
      phosphatidylglycerol, monoglycosyldiglyceride, three unidentified phospholipids,
      and one unidentified glycolipid. Glucuronopyranosyldiglyceride was present as a
      minor compound. The diagnostic diamino acid of the peptidoglycan was meso
      diaminopimelic acid. The genomic DNA G+C content was 52.8 mol%. Based on the
      genotypic, chemotaxonomic, and phenotypic analyses, strain MAA42T represents a
      novel species of the genus Litorimonas, for which the name Litorimonas haliclonae
      is proposed. The type strain is MAA42T (=CCM 8709T=CIP 111178T=LMG 29765T).

PMID- 29458472
TI  - Polyphasic data support the splitting of Aspergillus candidus into two species;
      proposal of Aspergillus dobrogensis sp. nov.
AB  - Aspergillus candidus is a species frequently isolated from stored grain, food,
      indoor environments, soil and occasionally also from clinical material. Recent
      bioprospecting studies highlighted the potential of using A. candidus and its
      relatives in various industrial sectors as a result of their significant
      production of enzymes and bioactive compounds. A high genetic variability was
      observed among A. candidus isolates originating from various European countries
      and the USA, that were mostly isolated from indoor environments, caves and
      clinical material. The A. candidus sensu lato isolates were characterized by DNA
      sequencing of four genetic loci, and agreement between molecular species
      delimitation results, morphological characters and exometabolite spectra were
      studied. Classical phylogenetic methods (maximum likelihood, Bayesian inference)
      and species delimitation methods based on the multispecies coalescent model
      supported recognition of up to three species in A. candidus sensu lato. After
      evaluation of phenotypic data, a broader species concept was adopted, and only
      one new species, Aspergillus dobrogensis, was proposed. This species is
      represented by 22 strains originating from seven countries (ex-type strain CCF
      4651T=NRRL 62821T=IBT 32697T=CBS 143370T) and its differentiation from A.
      candidus is relevant for bioprospecting studies because these species have
      different exometabolite profiles. Evaluation of the antifungal susceptibility of
      section Candidi members to six antifungals using the reference EUCAST method
      showed that all species have low minimum inhibitory concentrations for all tested
      antifungals. These results suggest applicability of a wide spectrum of antifungal
      agents for treatment of infections caused by species from section Candidi.

PMID- 29458473
TI  - Epidermidibacterium keratini gen. nov., sp. nov., a member of the family
      Sporichthyaceae, isolated from keratin epidermis.
AB  - A novel actinobacterial strain, designated EPI-7T, was isolated on R2A agar from
      human skin (keratinocytes) and subjected to a taxonomic study using a polyphasic
      approach. Strain EPI-7T showed a Gram-positive reaction, was non-motile, non
      spore-forming, and cells had a rod-shape. Colonies were round, convex and pale
      yellow. Phylogenetic analysis based on 16S rRNA gene sequences showed that the
      novel isolate formed a cluster with several uncultured bacterial clones and with
      cultured members of the genera Modestobacter and Sporichthya. The 16S rRNA gene
      sequence similarities with respect to the type strains of recognized species from
      the above genera and other phylogenetic neighbours ranged from 92.6 to 93.4 %.
      The G+C content of the genomic DNA was 68.9 mol%. The only isoprenoid quinone was
      MK-9(H4), and the major fatty acids detected were C17 : 1omega8c, C16 : 0, iso
      C15 : 0 and summed feature 3. The major polar lipids were found to be
      phosphatidylethanolamine, phosphatidylinositol, three unidentified phospholipids,
      phosphatidylglycerol, phosphatidylcholine, two unidentified amino lipids and
      three unidentified lipids. The cell-wall peptidoglycan contained meso
      diaminopimelic acid, glutamic acid and alanine. Whole-cell sugars present
      included rhamnose, glucose and galactose. The combination of the genotypic and
      phenotypic data allowed differentiation of strain EPI-7T from its closest
      phylogenetic neighbours and provided evidence that strain EPI-7T represents a
      novel genus and species in the family Sporichthyaceae. The name
      Epidermidibacterium keratini gen. nov., sp. nov. is proposed with the type strain
      being EPI-7T (=KCCM 90264T=JCM 31644T).

PMID- 29458474
TI  - Roseomonas fluminis sp. nov. isolated from sediment of a shallow stream.
AB  - An aerobic, Gram-negative, motile by means of a single polar flagellum, and ovoid
      shaped bacterium, designated D3T, was isolated from shallow stream sediments in
      Sinan-gun, South Korea. Growth occurred at 15-40  degrees C (optimum 35  degrees
      C), at pH 7.0-8.0 (optimum pH 7.0), and at an optimum NaCl concentration of 0.5 %
      (w/v). The major cellular fatty acids (>7 % of the total) were C16 : 0, C18 : 0 2
      OH, summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and summed feature 8
      (C18 : 1omega7c and/or C18 : 1omega6c). The predominant quinone was ubiquinone
      10, and the G+C content of the genomic DNA of strain D3T was 73.1 mol%. The major
      polyamine was spermidine. The major polar lipids of the isolate were
      diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and
      phosphatidylglycerol. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that strain D3T clustered with Roseomonas aquatica TR53T within the
      genus Roseomonas. The 16S rRNA gene sequence of strain D3T showed the highest
      sequence similarity to R. aquatica TR53T (95.9 %), followed by Roseomonas rosea
      173-96T (95.7 %) and Roseomonas aerilata 5420S-30T (95.0 %). Based on the
      phenotypic, phylogenetic and chemotaxonomic characterization, strain D3T
      represents a novel species of the genus Roseomonas, for which the name Roseomonas
      fluminis sp. nov. is proposed. The type strain is D3T (=KACC 19269T=JCM 31968T).

PMID- 29458475
TI  - Ornithinibacillus salinisoli sp. nov., a moderately halophilic bacterium isolated
      from a saline-alkali soil.
AB  - A taxonomic study was performed on strain LCB256T, which was isolated from a
      saline-alkali soil sample taken from northwestern China. Cells of strain LCB256T
      were Gram-stain-positive, aerobic, rod-shaped and grew at 3-17 % (w/v) NaCl
      (optimum 10-15 %), 10-52  degrees C (optimum 25-30  degrees C) and pH 7.0-9.0
      (optimum 8.0). Phylogenetic analysis based on 16S rRNA gene sequences indicated
      that strain LCB256T was most closely related to the two genera of
      Ornithinibacillus and Oceanobacillus, showing highest sequence similarity to
      Oceanobacillus limi KCTC 13823T (97.8 %) and Ornithinibacillus bavariensis WSBC
      24001T (97.2 %). The peptidoglycan amino acid type was found to be A4beta and the
      major respiratory quinone was determined to be MK-7. The polar lipid profile of
      strain LCB256T contained diphosphatidylglycerol, phosphatidylglycerol, one
      unidentified phospholipid and two unidentified aminolipids. The dominant cellular
      fatty acids were anteiso-C15 : 0 and iso-C15 : 0. The G+C content of genomic DNA
      was 39.3 mol%. DNA-DNA relatedness values between strain LCB256T and
      Ornithinibacillus halophilus KCTC 13822T and Oceanobacillus limi KCTC 13823T were
      46.2 and 34.8 %, respectively. Based on this polyphasic taxonomic study, a novel
      species of the genus Ornithinibacillus, Ornithinibacillussalinisoli sp. nov. is
      proposed. The type strain is LCB256T (=CGMCC 1.15809T=KCTC 33862T).

PMID- 29458476
TI  - Bacillus lacus sp. nov., isolated from a water sample of a salt lake in India.
AB  - A strictly aerobic, alkaliphilic, Gram-stain-positive, motile, rod-shaped
      bacterium, designated strain AK74T, was isolated from a water sample collected
      from Sambhar salt lake, Rajasthan, India. Colonies were circular, 1.2 mm in
      diameter, shiny, smooth, whitish and convex with an entire margin after 48 h
      growth at 37  degrees C with pH 9.0. Growth occurred at 25-42  degrees C, 0-4 %
      (w/v) NaCl and at a pH of 7-12. Strain AK74T was positive for aesculinase,
      caseinase, lipase activities and negative for oxidase, catalase, amylase,
      cellulase, DNase, gelatinase and urease activities. The fatty acids were
      dominated by branched iso-, anteiso- and saturated fatty acids with a high
      abundance of iso-C15 : 0, anteiso-C15 : 0, C16 : 0 and C16 : 1 and the cell-wall
      peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino acid.
      The DNA G+C content of strain AK74T was 51.6 mol%. A blast sequence similarity
      search based on 16S rRNA gene sequences indicated that Bacillus niabensis,
      Bacillus idriensisand Bacillus halosaccharovorans were the nearest phylogenetic
      neighbours, with a pair-wise sequence similarities of 96.6, 96.6 and 96.5%,
      respectively. Phylogenetic analysis showed that strain AK74T clustered with
      Bacillus mangrove and together clustered with Bacillus idriensisand Bacillus
      indicus. Based on its phenotypic characteristics and on phylogenetic inference,
      strain AK74T represents a novel species of the genus Bacillus, for which the name
      Bacilluslacus sp. nov. is proposed. The type strain is AK74T (=MTCC 12638T=KCTC
      33946T=JCM 32185T).

PMID- 29458477
TI  - Euzebyella algicola sp. nov., a marine bacterium of the family Flavobacteriaceae,
      isolated from green algae.
AB  - A Gram-negative, yellow-pigmented, non-flagellated, gliding, rod-shaped and
      aerobic bacterium, designated MEBiC 12267T, was isolated from green algae of Jeju
      Island. 16S rRNA gene sequence analysis revealed that the strain MEBiC 12267T was
      affiliated to the genus Euzebyella of the family Flavobacteriaceae and showed the
      highest similarity to Euzebyella marina KCTC 42440T (98.5 %). The DNA-DNA
      relatedness value of strain MEBiC 12267T with E. marina KCTC 42440T was 25 %.
      Growth was observed at 10-37  degrees C (optimum, 30-33  degrees C), at pH 6.0
      9.5 (optimum, 8.0-8.5) and with 0.5-9.0 % (w/v) NaCl (optimum, 2.5-3.5 %). The
      predominant cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0
      3-OH. The major respiratory quinone was MK-6. Polar lipids included
      phosphatidylethanolamine, seven unidentified lipids and two unidentified
      aminolipids. The DNA G+C content was 40.7 mol%. On the basis of the data from the
      polyphasic taxonomic study, it was concluded that the strain MEBiC 12267T
      represents a novel species within the genus Euzebyella, for which the name
      Euzebyella algicola sp. nov. is proposed. The type strain of E. algicola is MEBiC
      12267T (=KCCM 43264T=JCM 32170T).

PMID- 29458478
TI  - Tsukamurella ocularis sp. nov. and Tsukamurella hominis sp. nov., isolated from
      patients with conjunctivitis in Hong Kong.
AB  - Three bacterial strains, HKU63T, HKU64 and HKU65T, were isolated from the
      conjunctival swabs of three patients with conjunctivitis in Hong Kong. The three
      strains were aerobic, Gram-stain-positive, catalase-positive, non-sporulating and
      non-motile bacilli and exhibited unique biochemical profiles distinguishable from
      closely related Tsukamurella species. 16S rRNA gene sequence analysis revealed
      that the three strains shared identical sequences with each other, being most
      closely related to Tsukamurella tyrosinosolvens and Tsukamurella pulmonis,
      sharing 99.9 % sequence identity. Sequence analysis of three additional
      housekeeping genes, groEL, secA and rpoB, revealed 100 % nucleotide sequence
      identity between HKU63T and HKU64, 94.2-97.0 % nucleotide sequence identities
      between HKU63T/HKU64 and HKU65T and the three strains shared 82.9-98.9 % sequence
      identities with other currently recognized Tsukamurella species. DNA-DNA
      hybridization confirmed that they were distinct from other known species of the
      genus Tsukamurella(23.0+/-4.2 to 50.7+/-3.7 % DNA-DNA relatedness), of which
      HKU63T and HKU64 represented the same species (>=95.2+/-4.8 % DNA-DNA
      relatedness) while HKU65T represented another species. Fatty acid, mycolic acid,
      cell-wall sugar and peptidoglycan analyses showed that they were typical of
      members of Tsukamurella. The G+C content of strains HKU63T, HKU64 and HKU65T were
      71.3+/-1.9, 71.3+/-2.0 and 71.2+/-2.3 mol% (mean+/-sd; n=3), respectively. A
      novel species, Tsukamurella ocularis sp. nov. is proposed to accommodate strains
      HKU63T and HKU64, with HKU63T (=JCM 31969T=DSM 105034T) designated as the type
      strain whilst another novel species, Tsukamurella hominis sp. nov., is proposed
      to accommodate the third strain, HKU65T, which is designated as the type strain
      (=JCM 31971T=DSM 105036T).

PMID- 29458479
TI  - Listeria costaricensis sp. nov.
AB  - A bacterial strain isolated from a food processing drainage system in Costa Rica
      fulfilled the criteria as belonging to the genus Listeria, but could not be
      assigned to any of the known species. Phylogenetic analysis based on the 16S rRNA
      gene revealed highest sequence similarity with the type strain of Listeria
      floridensis (98.7 %). Phylogenetic analysis based on Listeria core genomes placed
      the novel taxon within the Listeria fleishmannii, L. floridensis and Listeria
      aquatica clade (Listeria sensu lato). Whole-genome sequence analyses based on the
      average nucleotide blast identity (ANI<80 %) indicated that this isolate belonged
      to a novel species. Results of pairwise amino acid identity (AAI>70 %) and
      percentage of conserved proteins (POCP>68 %) with currently known Listeria
      species, as well as of biochemical characterization, confirmed that the strain
      constituted a novel species within the genus Listeria. The name Listeria
      costaricensis sp. nov. is proposed for the novel species, and is represented by
      the type strain CLIP 2016/00682T (=CIP 111400T=DSM 105474T).

PMID- 29458480
TI  - Chryseobacterium glaciei sp. nov., isolated from the surface of a glacier in the
      Indian trans-Himalayas.
AB  - A novel bacterial strain, IHBB 10212T, of the genus Chryseobacterium was isolated
      from a glacier near the Kunzum Pass located in the Lahaul-Spiti in the North
      Western Himalayas of India. The cells were Gram-negative, aerobic, non
      sporulating, single rods, lacked flagella, and formed yellow to orange pigmented
      colonies. The strain utilized maltose, trehalose, sucrose, gentibiose, glucose,
      mannose, fructose, mannitol, arabitol and salicin for growth. Flexirubin-type
      pigments were produced by strain IHBB 10212T. The 16S rRNA gene sequence analysis
      showed relatedness of strain IHBB 10212T to Chryseobacterium polytrichastri DSM
      26899T (97.43 %), Chryseobacterium greenlandense CIP 110007T (97.29 %) and
      Chryseobacterium aquaticum KCTC 12483T (96.80 %). Iso-C15 : 0 and summed feature
      3 (C16 : 1omega7c/C16 : 1omega6c) constituted the major cellular fatty acids. The
      polar lipids present were six unidentified aminolipids, one unidentified
      phospholipid and three unidentified lipids. MK-6 was identified as the major
      quinone. The DNA G+C content was 34.08  mol%. Digital DNA-DNA hybridization of
      strain IHBB 10212T with C. polytrichastri, C. greenlandense and C. aquaticum
      showed values far below the prescribed thresholds of 95 % for average nucleotide
      identity and 70 % for the Genome-to-Genome Distance Calculator for species
      delineation. Based on its differences from validly published Chryseobacterium
      species, strain IHBB 10212T is identified as a new species, for which the
      proposed name is Chryseobacterium glaciei sp. nov., with IHBB 10212T as the type
      strain (=MTCC 12457T=JCM 31156T=KACC 19170T).

PMID- 29458481
TI  - Dokdonia flava sp. nov., isolated from the seaweed Zostera marina.
AB  - A non-motile, proteorhodopsin-containing, yellow and rod-shaped bacterial strain,
      designated ZODW10T, was isolated from the seaweed Zostera marina collected from
      the West Sea, Republic of Korea. Cells were Gram-stain-negative, aerobic and non
      motile. The isolate required sea salts for growth. A carotenoid pigment was
      produced. A phylogenetic tree based on 16S rRNA gene sequences showed that strain
      ZODW10T forms an evolutionary lineage within the radiation enclosing members of
      the genus Dokdonia with Dokdoniadiaphoros CIP 108745T (96.7 % sequence
      similarity) as its nearest neighbour. The major fatty acids were iso-C15:0, iso
      C17 : 0 3-OH and iso-C15 : 1 G. Strain ZODW10T contained menaquinone 6 (MK-6) and
      phosphatidylethanolamine, an unidentified aminolipid and an unidentified polar
      lipid as the only isoprenoid quinone and the major polar lipids, respectively.
      The DNA G+C content of strain ZODW10T was 36 mol%. On the basis of the present
      polyphasic characterization, it is suggested that the isolate represents a novel
      species of the genus Dokdonia, for which the name Dokdonia flava sp. nov. (type
      strain, ZODW10T=KCTC 52953T=JCM 32293T) is proposed.

PMID- 29458482
TI  - Sphingobacterium solani sp. nov., isolated from potato stems.
AB  - A Gram-stain-negative, non-motile, non-spore-forming bacterium, designated MLS-26
      JM13-11T, was isolated from potato stems, collected in Guyuan County, Hebei
      Province, China. Strain MLS-26-JM13-11T could grow at 10-39  degrees C (optimum,
      30  degrees C), pH 6.0-9.0 (optimum, pH 7.2) and in the presence of 0-4.0 % (w/v)
      NaCl (optimum, 1.0 % w/v). Phylogenetic analysis, based on 16S rRNA gene
      sequences, revealed that strain MLS-26-JM13-11T formed a stable clade with
      Sphingobacterium bambusae IBFC2009T and Sphingobacterium griseoflavum SCU-B140T,
      with the 16S rRNA gene sequence similarities ranging from 95.9 % to 97.0 %. The
      major cellular fatty acids comprised iso-C15 : 0 (36.9 %), summed feature 3 (C16
      : 1omega7c and/or C16 : 1omega6c, 34.0 %), C16 : 0 (3.0 %) and iso-C17 : 0 3-OH
      (13.4 %). Strain MLS-26-JM13-11T contained sphingoglycolipid, phosphatidyl
      ethanolamine, six unknown lipids, one unknown aminolipid, four unknown
      polarlipids and two unknown aminophospholipids. The isoprenoid quinone was MK-7.
      The DNA G+C content was 42.6 mol%. Furthermore, the average nucleotide identity
      and in silico estimated DNA-DNA reassociation values among MLS-26-JM13-11T and S.
      bambusae KCTC 22814T were in all cases below the respective threshold for species
      differentiation. On the basis of phenotypic, genotypic and phylogenetic evidence,
      strain MLS-26-JM13-11T (=ACCC 60057T=JCM 32274T) represents a novel species
      within the genus Sphingobacterium, for which the name Sphingobacterium solani sp.
      nov. is proposed.

PMID- 29458483
TI  - Marinicrinis lubricantis sp. nov., isolated from a coolant lubricant.
AB  - A Gram-stain-positive, aerobic, endospore-forming bacterium isolated from a
      coolant lubricant was studied for its taxonomic allocation. On the basis of 16S
      rRNA gene sequences, strain KSS164-79T shared highest similarity (92.3-92.4 %) to
      type strains of the species Marinicrinis sediminis,Paenibacillus dongdonensis,
      Paenibacillus abyssi and Paenibacillus motobuensis. In phylogenetic trees based
      on the 16S rRNA gene, strain KSS164-79T always formed a distinct cluster with the
      type strain of M. sediminis. The fatty acid profile supported the grouping of the
      strain to the genus Marinicrinis. As major fatty acids, anteiso-C15 : 0, iso-C15
      : 0 and iso-C16 : 0 were detected. The polar lipid profile contained the major
      components diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine
      and two unidentified glycolipids. The major quinone was menaquinone MK-7. In
      addition, physiological and biochemical test results allowed the clear phenotypic
      differentiation of strain KSS164-79T from M. sediminis. Hence, KSS164-79T
      represents a novel species of the genus Marinicrinis, for which the name
      Marinicrinis lubricantis sp. nov. is proposed, with KSS164-79T (=DSM 104943T=LMG
      30062T=CCM 8749T=CIP 111345T) as the type strain.

PMID- 29458484
TI  - Flavisolibacter metallilatus sp. nov., isolated from an automotive air
      conditioning system and emended description of the genus Flavisolibacter.
AB  - A Gram-stain-negative, aerobic, non-motile, rod-shaped and pale yellow-pigmented
      bacterium, designated strain TX0661T, was isolated from an automotive air
      conditioning system collected in the Republic of Korea. 16S rRNA gene sequence
      analysis showed that the strain TX0661T was grouped with members of the genus
      Flavisolibacter and the strain had 98.2-95.3 % 16S rRNA gene sequence
      similarities to the species of the genus Flavisolibacter. DNA-DNA relatedness
      between TX0661T and Flavisolibacter ginsenosidimutans KCTC 22818T and
      Flavisolibacter ginsengisoli KCTC 12657T was less than 30 %. The low levels of
      DNA-DNA relatedness identified strain TX0661T as a novel species in the genus
      Flavisolibacter. The strain grew at 28-37  degrees C (optimum, 37  degrees C), at
      pH 6.0-7.0 (optimum, pH 6.5) and in the presence of 0-0.5 % (w/v, optimum, 0.5 %)
      NaCl. It contained summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c), iso
      C15 : 0 and iso-C17 : 0 3-OH as major fatty acids and MK-7 as the predominant
      menaquinone. The polar lipid profile revealed that the presence of
      phosphatidylethanolamine, aminoglycophospholipid, two unidentified aminolipids
      and two unidentified lipids. The DNA G+C content of the strain was 49.1 mol%.
      Based on phenotypic, genotypic and chemotaxonomic data, strain TX0661T represents
      a novel species in the genus Flavisolibacter, for which the name
      Flavisolibactermetallilatus sp. nov. (=KACC 19145T=KCTC 52779T=NBRC 111784T) is
      proposed.

PMID- 29458485
TI  - Aquimarina algiphila sp. nov., a chitin degrading bacterium isolated from the red
      alga Tichocarpus crinitus.
AB  - A strictly aerobic, Gram-stain-negative, rod-shaped, motile by gliding and yellow
      orange pigmented flavobacterium, designated strain 9Alg 151T, was isolated from
      the Pacific red alga Tichocarpus crinitus. Phylogenetic analysis based on 16S
      rRNA gene sequences showed that the novel strain fell into the genus Aquimarina
      of the family Flavobacteriaceae with a 16S rRNA gene sequence similarity range of
      94.2-98.2 % to the recognized species of the genus. Strain 9Alg 151T grew in the
      presence of 0.5-5 % NaCl and at 5-34  degrees C, and hydrolysed aesculin, agar,
      gelatin, starch, Tween 40, DNA and chitin. The predominant fatty acids were iso
      C17 : 0 3-OH, iso-C15 : 0, iso-C15 : 1 G, iso-C15 : 0 3-OH, iso-C16 : 0, iso-C17
      : 1omega8c and summed feature 3. The polar lipid profile comprised
      phosphatidylethanolamine, three unidentified aminolipids and three unidentified
      lipids. The major respiratory quinone was MK-6. The genomic DNA G+C content was
      32.6 mol%. On the basis of 16S rRNA gene sequence data, and chemotaxonomic and
      phenotypic characteristics, strain 9Alg 151T represents a novel species of the
      genus Aquimarina, for which the name Aquimarina algiphila sp. nov. is proposed.
      The type strain is 9Alg 151T (=KCTC 23622T=KMM 6462T).

PMID- 29458486
TI  - Muricauda indica sp. nov., isolated from deep sea water.
AB  - A taxonomic study was carried out on strain 3PC125-7T, which was isolated from
      the deep sea water of the Indian Ocean. The bacterium was rod-shaped, non
      flagellated, Gram-stain-negative, oxidase- and catalase-positive and strictly
      aerobic. Optimal growth was observed at 25-37  degrees C, at pH 7 and in 1-3 %
      (w/v) NaCl. On the basis of the results of 16S rRNA gene sequence analysis,
      strain 3PC125-7T represents a member of the genus Muricauda, with the highest
      sequence similarity to Muricauda olearia CL-SS4T (96.7 %), followed by Muricauda
      marina H19-56T (96.7 %) and nine other species of the genus Muricauda(93.5-95.8
      %). The principal fatty acids of 3PC125-7T were iso-C15 : 0, iso-C17 : 0 3-OH and
      iso-C15 : 1G and the sole respiratory quinone was menaquinone-6. The polar lipids
      comprise phosphatidylethanolamine, six unidentified phospholipids and three
      unknown lipids. The genomic DNA G+C content of 3PC125-7T was 41.8 mol%. Based on
      the phylogenetic, phenotypic and chemotaxonomic data obtained in this study,
      strain 3PC125-7T is considered to represent a novel species in the genus
      Muricauda, for which the name Muricaudaindica sp. nov. is proposed, with the type
      strain 3PC125-7T (=MCCC 1A03198T=KCTC 52318T).

PMID- 29458487
TI  - Defluviimonas pyrenivorans sp. nov., a novel bacterium capable of degrading
      polycyclic aromatic hydrocarbons.
AB  - An aerobic, Gram-stain-negative, rod-shaped, non-motile bacterium capable of
      degrading the polycyclic aromatic hydrocarbon pyrene was isolated from sediment
      of Pearl River and designated PrR001. 16S rRNA gene sequence analysis revealed
      that this strain was affiliated within the genus Defluviimonas in the family
      Rhodobacteraceae of the class Alphaproteobacteria and showed great similarity
      with the type strain Defluviimonas indica 20V17T (96.3 % similarity). The DNA G+C
      content of strain PrR001T was 68.3 mol%. The major cellular fatty acids comprised
      summed feature 8 (C18 : 1omega7c/C18 : 1omega6c), C19 : 0 cyclo omega8c, C18 : 0
      3OH, and C18 : 0. The sole respiratory lipoquinone was ubiquinone-10. The main
      polar lipids were diphosphatidylglycerol, phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylglycerol, an unidentified aminolipid, an
      unidentified aminophospholipid and three unidentified phospholipids. Based on
      physiological, chemotaxonomic and phylogenetic analysis, strain PrR001T is
      suggested as a novel species in the genus Defluviimonas, for which the name
      Defluviimonas pyrenivorans sp. nov. is proposed. The type strain of Defluviimonas
      pyrenivorans is PrR001T (=CICC 24263T=KCTC 62192T).

PMID- 29458488
TI  - Flavobacterium kingsejongi sp. nov., a carotenoid-producing species isolated from
      Antarctic penguin faeces.
AB  - Taxonomic studies were carried out on a carotenoid-producing strain, designated
      WV39T, isolated from the faeces of Antarctic penguins. Cells of strain WV39T were
      Gram-stain-negative, strictly aerobic, yellow and rod-shaped. 16S rRNA gene
      sequence analysis revealed that strain WV39T was closely related to
      Flavobacterium qiangtangense JCM 19739T (96.3 % similarity), Flavobacterium
      noncentrifugens NBRC 108844T (95.5 %) and Flavobacterium aquatile LMG 4008T (94.9
      %). The predominant cellular fatty acids were iso-C15 : 0, iso-C15 : 0 3-OH and
      summed feature 3 (comprising iso-C15 : 0 2-OH and/or C16 : 1omega7c). Menaquinone
      6 was the sole quinone identified, and the major pigment was zeaxanthin. The
      major polar lipid was phosphatidylethanolamine. DNA-DNA relatedness of strain
      WV39T with respect to its closest phylogenetic neighbours was 41.8 % for F.
      qiangtangense JCM 19739T, 25.5 % for F. aquatile LMG 4008T and 25.2 % for F.
      noncentrifugens NBRC 108844T. The DNA G+C content of strain WV39T was 39.8 mol%.
      Based on the phenotypic, chemotaxonomic and phylogenetic data, strain WV39T is
      concluded to represent a novel species of the genus Flavobacterium, for which the
      name Flavobacteriumkingsejongi sp. nov. is proposed. The type strain is WV39T
      (=KCTC 42908T=CECT 9085T).

PMID- 29458489
TI  - Microbacterium telephonicum sp. nov., isolated from the screen of a cellular
      phone.
AB  - A cultivation-based study of the microbial diversity of cellular phone screens
      led to the isolation of a Gram-stain-positive, aerobic, rod-shaped and non
      endospore-forming bacterium, designated S2T63T, exhibiting phenotypic and
      genotypic characteristics unique to the type strains of closely related species.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain
      is a member of Microbacterium, and most closely related to Microbacterium
      aurantiacum IFO 15234T and Microbacterium kitamiense Kitami C2T. The DNA-DNA
      relatedness values of the strain S2T63T to M. aurantiacum KACC 20510T, M.
      kitamiense KACC 20514Tand Microbacterium laevaniformans KACC 14463T were 65 % (+/
      4), 29.5 % (+/-3) and 55.9 % (+/-4), respectively. The genomic DNA G+C content
      was 71.8 mol%. The major fatty acids were anteiso-C15 : 0, iso-C16 : 0, C16 : 0
      and anteiso-C17 : 0. The main polar lipids were diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol and two unidentified polar lipids.
      The peptidoglycan contained the amino acids glycine, lysine, alanine and glutamic
      acid, with substantial amounts of hydroxy glutamic acid detected, which is
      characteristic of peptidoglycan type B1alpha. The predominant menaquinones were
      MK-12 and MK-13. Rhamnose, fucose and galactose were the whole-cell sugars
      detected. The strain also showed biofilm production, estimated by using crystal
      violet assay. Based on the results of the phenotypic and genotypic
      characterizations, it was concluded that the new strain represents a novel
      species of the genus Microbacterium, for which the name
      Microbacteriumtelephonicum is proposed, with S2T63T (=MCC 2967T=KACC 18715T=LMG
      29293T) as the type strain.

PMID- 29458490
TI  - Halioglobus lutimaris sp. nov., isolated from coastal sediment.
AB  - A novel Gram-stain-negative, strictly aerobic, non-flagellated and rod-shaped
      bacterium, designated HF004T, was isolated from a marine sediment sample
      collected from the coast of Weihai, China. The strain grew optimally at 28 
      degrees C, pH 7.5-8.0 and in the presence of 2.0-3.0 % (w/v) NaCl. Based on the
      16S rRNA gene sequence analysis, strain HF004T was a member of the genus
      Halioglobus, appearing to be closely related to Halioglobus pacificus (96.1 %)
      and Halioglobus japonicus (95.6 %). The major fatty acids were summed feature 3
      (i.e. C16 : 1omega7c and/or iso-C15 : 0 2-OH), C17 : 1omega8c and C18 : 1omega7c.
      The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and
      phosphatidylglycerol. The predominant respiratory quinone was Q-8. The DNA G+C
      content was 57.2 mol%. Cells of strain HF004T were rod-shaped and formed
      circular, mucous and beige-pigmented colonies on marine agar after incubation for
      72 h at 28  degrees C. On the basis of phenotypic, genotypic and phylogenetic
      evidence, strain HF004T is presented as a novel species, for which the name
      Halioglobus lutimaris sp. nov. is proposed. The type strain is HF004T (=KCTC
      42395T=MCCC 1H00127T).

PMID- 29458491
TI  - Micromonospora globbae sp. nov., an endophytic actinomycete isolated from roots
      of Globba winitii C. H. Wright.
AB  - A novel endophytic actinomycete, strain WPS1-2T, isolated from a root of Globba
      winitii C. H. Wright, was characterized taxonomically by using a polyphasic
      approach. Strain WPS1-2T exhibited identical characteristics to the members of
      the genus Micromonospora. Single spores were observed directly on substrate
      mycelia. The cell-wall peptidoglycan of the strain contained meso-diaminopimelic
      acid and 3-OH-meso-diaminopimelic acid. Whole-cell hydrolysates contained
      glucose, ribose, arabinose and xylose. The predominant menaquinones were MK
      10(H8) and MK-10(H10). The major cellular fatty acids consisted of iso-C15 : 0,
      iso-C16 : 0 and anteiso-C15 : 0. According to the 16S rRNA gene sequence of the
      strain, WPS1-2T showed highest similarity to Micromonospora costi CS1-12T (99.02
      %). Phylogenetic analysis of the gyrase subunit B (gyrB) gene indicated that the
      strain was related to M. costi CS1-12T. The DNA G+C content was 73.7 mol%. The
      strain could be distinguished from closely related type strains by using a
      combination of morphological, chemotaxonomic, physiological and biochemical data
      together with DNA-DNA relatedness values. Based on these observations, strain
      WPS1-2T is considered to represent a novel species of the genus Micromonospora,
      for which the name Micromonospora globbae sp. nov. is proposed. The type strain
      is WPS1-2T (=KCTC 39787T=NBRC 112325T=TISTR 2405T).

PMID- 29458492
TI  - Acinetobacter piscicola sp. nov., isolated from diseased farmed Murray cod
      (Maccullochella peelii peelii).
AB  - A taxonomic study was carried out on strain LW15T, which was isolated from the
      external lesions of diseased farmed Murray cod (Maccullochella peelii peelii)
      from an intensive culture pond. Cells of strain LW15T were Gram-negative,
      facultative-anaerobic, non-motile, and both coccobacillus- and bacillus-shaped.
      Growth was observed at NaCl concentrations of 0-2 % (w/v) (optimum, 0 %), 4-32 
      degrees C (optimum, 25-28  degrees C) and pH 5.0-9.0 (optimum, 7.0). Phylogenetic
      analysis based on 16S rRNA gene sequences indicated that strain LW15T was
      affiliated to the genus Acinetobacter, showing the highest similarity to
      Acinetobacter guillouiae CIP 63.46T (97.7 %) and other Acinetobacter species with
      validly published names (93.5-97.6 %). Whole-genome sequencing and phylogeny
      reconstruction based on a core set of 1061 Acinetobacter genes indicated that
      strain LW15T was most closely related to the clade formed by A. guillouiae CIP
      63.46T and Acinetobacter bereziniae CIP 70.12T and distantly related to any of
      the described species of genus Acinetobacter. Furthermore, strain LW15T could be
      distinguished from all known Acinetobacter species by its ability to assimilate
      beta-alanine and l-arginine, but not d-glucose. The principal fatty acids were
      C18 : 1omega9c, C16 : 0 and C16 : 1omega7c/C16 : 1omega6c. The major respiratory
      quinone was Q-9. Polar lipids of strain LW15T comprised diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, four
      phospholipids, aminolipid and two unknown lipids. Based on its phenotypic and
      genotypic data, strain LW15T represents a novel species of the genus
      Acinetobacter, for which the name Acinetobacterpiscicola sp. nov. is proposed.
      The type strain is LW15T (=MCCC 1K03337T=CICC 24241T=KCTC 62134T=JCM 32101T).

PMID- 29458493
TI  - Blautia hominis sp. nov., isolated from human faeces.
AB  - A strictly anaerobic, Gram-stain-positive, non-motile and coccoid- or oval-shaped
      bacterium, designated strain KB1T, was isolated from a faecal sample of a patient
      with diverticulitis in South Korea. Degeneracies in the 16S rRNA gene sequence of
      strain KB1T were resolved by cloning, which yielded five different sequences with
      heterogeneity. Phylogenetic analysis based on the 16S rRNA gene sequences showed
      that strain KB1T formed a monophyletic branch with species in the genus Blautia,
      with highest sequence similarity to the type strain of Blautia producta (97.7
      98.9 %), followed by Blautia coccoides (97.5-98.1 %). Strain KB1T was able to
      grow at temperatures of between 15 and 42  degrees C, with optimal growth at 37 
      degrees C, and in the presence of 20 % dehydrated bile. Acetic acid, succinic
      acid, lactic acid and fumaric acid were produced by strain KB1T from Gifu
      anaerobic medium broth as metabolic fermentation end-products. The major cellular
      fatty acids of strain KB1T were C14 : 0, C16 : 0 and C16 : 0 dimethyl aldehyde.
      The DNA G+C content was 46.3 mol%. The average nucleotide identity value between
      strain KB1T and the type strain of B. producta was 84.1 %. On the basis of
      polyphasic analysis, strain KB1T represents a novel species in the genus Blautia,
      for which the name Blautia hominis sp. nov. is proposed. The type strain is KB1T
      (=KCTC 15618T=JCM 32276T).

PMID- 29458495
TI  - Simplicispira soli sp. nov., a betaproteobacterium isolated from stream bank
      soil.
AB  - Two strains of soil bacteria, designated CA-16T and CA-161, were isolated from a
      sample of stream bank soil near Kyonggi University. Cells were strictly aerobic,
      Gram-stain-negative, catalase-negative, oxidase-positive, motile, non-spore
      forming and rod-shaped. Colonies on tryptone soya agar were brownish cream in
      colour. Tyrosine, Tween 60 and Tween 40 were hydrolysed. The indole test was
      positive. Malic acid, lactic acid and valeric acid were assimilated. Phylogenetic
      analysis based on their 16S rRNA gene sequences revealed that strains CA-16T and
      CA-161 formed a lineage within the family Comamonadaceae of the class
      Betaproteobacteria that were distinct from various species of the genus
      Simplicispira. Strain CA-16T was most closely related to Simplicispira metamorpha
      DSM 1837T (97.86 % sequence similarity), Simplicispira limi EMB325T (97.72 %),
      Simplicispira psychrophila DSM 11588T (96.83 %) and Simplicispira piscis RSG39T
      (96.71 %). Both strains contained Q-8 as the major isoprenoid quinone. The major
      polar lipids of the strains were phosphatidylglycerol, phosphatidylethanolamine
      and diphosphatidylglycerol. The major cellular fatty acids were summed feature 3
      (C16 : 1omega7c and/or C16 : 1omega6c), C18 : 1omega7c-11methyl, C16 : 0, summed
      feature 8 (C18 : 1omega7c and/or C18 : 1omega6c) and C12 : 0. The DNA G+C
      contents of the strains were 63.9-64.4 mol%. DNA-DNA hybridization similarities
      between strain CA-16T and other closest members of the genus Simplicispira ranged
      from 16 % to 24 %. On the basis of phenotypic, genotypic, chemotaxonomic and
      phylogenetic analyses, strains CA-16T and CA-161 represent a single novel species
      of the genus Simplicispira, for which the name Simplicispirasoli sp. nov. is
      proposed. The type strain is CA-16T (=KEMB 9005-529T=KACC 19107T=NBRC 112689T).

PMID- 29458494
TI  - Uliginosibacterium sediminicola sp. nov., isolated from freshwater sediment.
AB  - Strain M1-21T is a Gram-stain-negative, strictly aerobic and short-rod-shaped
      bacterium, motile by means of a single polar flagellum; it was isolated from
      freshwater sediment in Korea. It grew at 10-40  degrees C (optimum 25  degrees
      C), pH 6.0-8.0 (optimum pH 7.0) and with 0-0.75 % (w/v) NaCl (optimal growth
      occurred in the absence of NaCl) on R2A agar, and it accumulated poly-beta
      hydroxybutyrate granules inside the cells. According to 16S rRNA gene sequence
      analysis, strain M1-21T showed highest sequence similarity with
      Uliginosibacterium gangwonense (94.7 %) and Uliginosibacterium paludis (94.4 %).
      Phylogenetic analysis of the 16S rRNA gene sequences revealed that strain M1-21T
      belongs to the genus Uliginosibacterium. The DNA G+C content of strain M1-21T was
      61.9 mol%. The predominant respiratory quinone was ubiquinone-8. The major fatty
      acids (>10 % of the total) were C16 : 0 and summed feature 3 (C16 : 1omega6c
      and/or C16 : 1omega7c), and the major polar lipids were diphosphatidylglycerol,
      phosphatidylglycerol and phosphatidylethanolamine. Strain M1-21T showed distinct
      phenotypic characteristics that differentiated it from species of the genus
      Uliginosibacterium. Based on these results, strain M1-21T represents a novel
      species of the genus Uliginosibacterium, for which the name Uliginosibacterium
      sediminicola sp. nov. is proposed. The type strain is M1-21T (=KACC 19271T=JCM
      32000T).

PMID- 29458496
TI  - Halomonas malpeensis sp. nov., isolated from rhizosphere sand of a coastal sand
      dune plant.
AB  - A Gram-stain-negative, aerobic, non-endospore-forming organism, isolated from the
      rhizosphere sand of a coastal sand dune plant was studied for its taxonomic
      position. On the basis of 16S rRNA gene sequence similarity comparisons, strain
      YU-PRIM-29T was grouped within the genus Halomonas and was most closely related
      to Halomonas johnsoniae (97.5 %). The 16S rRNA gene sequence similarity to other
      Halomonas species was <97.5 %. Strain YU-PRIM-29T grew optimally at 28  degrees C
      (growth range, 10-36  degrees C), at a pH of 7-9 (growth range, pH 5.5-12.0) and
      in the presence of 0.5 to 5 % (w/v) NaCl (growth up to 20 % NaCl). The fatty acid
      profile from whole-cell hydrolysates supported the allocation of the strain to
      the genus Halomonas. The fatty acids C18 : 1omega7c and C16 : 0 were found as
      major compounds, followed by the hydroxylated fatty acid C12 : 0 3-OH. The
      quinone system consisted predominantly of ubiquinone Q-9. The polar lipid profile
      was composed of the major lipids diphosphatidylglycerol, phosphatidylglycerol and
      phosphatidylethanolamine. In the polyamine pattern, spermidine was the
      predominant compound. The DNA G+C content was 64.8 mol%. In addition, the results
      of physiological and biochemical tests also allowed phenotypic differentiation of
      strain YU-PRIM-29T from its closest-related species. Hence, YU-PRIM-29T
      represents a new species of the genus Halomonas, for which we propose the name
      Halomonas malpeensis sp. nov., with YU-PRIM-29T (=LMG 28855T=CCM 8737T) as the
      type strain.

PMID- 29458497
TI  - A novel genus of the class Actinobacteria, Longivirga aurantiaca gen. nov., sp.
      nov., isolated from lake sediment.
AB  - A novel actinobacterial strain, designated X5T, was isolated from the sediment of
      Taihu Lake in China and was subjected to a polyphasic taxonomic characterization.
      The strain formed orange-red colonies comprising aerobic, Gram-stain-negative,
      rod-shaped cells on R2A agar. Phylogenetic analysis based on the 16S rRNA gene
      sequences revealed that the organism was closely related to the genus Sporichthya
      and consistently formed a distinct clade along with the members of this genus.
      The closest phylogenetic neighbour was Sporichthya polymorpha NBRC 12702T with
      93.7 % 16S rRNA gene sequence similarity. The major fatty acids (>10 %) were iso
      C16 : 0 (18.7 %), C18 : 1omega9c (18.6 %) and C17 : 1omega8c (14.0 %). The
      genomic DNA G+C content was 74.4 mol%. The organism contained menaquinone MK
      8(H2), MK-9(H4) and an unidentified menaquinone. Polar lipids were composed of
      phosphatidylglycerol, an unidentified lipid, two unidentified phospholipids and
      two unidentified aminolipids. The whole-cell sugars contained ribose, xylose,
      mannose, glucose and galactose. The cell-wall peptidoglycan contained ll
      diaminopimelic acid. Based on the physiological, biochemical and chemotaxonomic
      data, the organism is proposed to represent a novel genus and species, for which
      the name Longivirga aurantiaca gen. nov., sp. nov. is proposed. The type strain
      is X5T (=CGMCC 4.7317T=NBRC 112237T).

PMID- 29458498
TI  - Actinorectispora metalli sp. nov., a novel actinomycete isolated from a mine and
      emended description of the genus Actinorectispora.
AB  - A novel actinomycete, designated strain KC 198T, was isolated from rare earth
      mine. The results of analysis of the 16S rRNA gene sequence indicated that KC
      198T was most closely related to Actinorectisporaindica YIM 75728T (98.4 %).
      Aerial hyphae differentiated into long, straight chains of cylindrical spores.
      Growth was observed at 10-45  degrees C (optimum 28  degrees C), with 0-10 %
      (w/v) NaCl (optimum, in the absence of NaCl) and at pH 6.0-8.0 (optimum pH 7.0).
      KC 198T possessed MK-9(H4) as the predominant respiratory quinone and a minor
      amount of MK-10(H4). Polar lipids detected were diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and
      phosphatidylinositol mannoside. Three unidentified lipids were also detected. The
      main cellular fatty acids were iso-C16 : 0 (30.9 %), iso-C16 : 1H (22.9 %) and
      iso-C15 : 0 (14.8 %). The genomic DNA G+C content was 66.8 mol%. On the basis of
      the phenotypic and genotypic characteristics, we propose that strain KC 198T
      represents a novel species of the genus Actinorectispora. The name
      Actinorectispora metalli sp. nov. is, therefore, proposed for the novel species
      with the type strain KC 198T (=CCTCC AA 2015043T=KCTC 39718T). The description of
      the genus Actinorectispora has also been emended.

PMID- 29458499
TI  - Proposal of the suffix -ota to denote phyla. Addendum to 'Proposal to include the
      rank of phylum in the International Code of Nomenclature of Prokaryotes'.
AB  - As an addendum to the earlier proposal to include the rank of phylum in the
      International Code of Nomenclature of Prokaryotes (Oren et al., Int J Syst Evol
      Microbiol 2015;65:4284-4287) we propose the suffix -ota to denote phyla,
      replacing the somewhat awkward -aeota. We therefore present a new draft modified
      version of Rule 8 of the International Code of Nomenclature of Prokaryotes and a
      corrected list of names of phyla to be considered for validation after approval
      of the proposal to include the rank of phylum in the Code.

PMID- 29458500
TI  - Proteiniborus indolifex sp. nov., isolated from a thermophilic industrial-scale
      biogas plant.
AB  - A novel strictly anaerobic bacterium, designated strain BA2-13T, was isolated
      from a thermophilic industrial-scale biogas plant. Cells were rod-shaped and Gram
      stain-positive. Growth occurred at temperatures of 25 to 50  degrees C and
      between pH 6.3 and 9.5. Strain BA2-13T produced indole. Cell growth was
      stimulated by yeast extract, peptone, meat extract, a mixture of 20 amino acids,
      glucose, pyruvate and ribose. When grown on peptone and yeast extract, the main
      fermentation products were acetic acid, H2 and CO2. The predominant cellular
      fatty acids were iso-C15 : 0 and iso-C14 : 0 3-OH. Major polar lipids were
      diphosphatidylglycerol, glycolipids, phospholipids and phosphatidylgycerol.
      Phylogenetic analysis based on 16S rRNA gene nucleotide sequence analysis placed
      strain BA2-13T within the order Clostridiales showing closest affiliation with
      Proteiniborusethanoligenes with 95.9 % sequence identity. Physiological,
      genotypic and chemotaxonomic differences of strain BA2-13T from P. ethanoligenes
      support the description of a new species within the genus Proteiniborus for which
      we suggest the name Proteiniborusindolifex sp. nov. (type strain BA2-13T=DSM
      103060T=LMG 29818T).

PMID- 29458501
TI  - Vibrio fujianensis sp. nov., isolated from aquaculture water.
AB  - A Gram-stain-negative, facultatively anaerobic strain, designated FJ201301T, was
      isolated from aquaculture water collected from Fujian province, China.
      Phylogenetic analysis of 16S rRNA gene sequences indicated that strain FJ201301T
      belonged to the genus Vibrio, formed a distinct cluster with
      Vibriocincinnatiensis ATCC 35912T and shared the highest similarity with
      Vibriosalilacus CGMCC 1.12427T. A 15 bp insertion found in the 16S rRNA gene was
      a significant marker that distinguished strain FJ201301T from several
      phylogenetic neighbours (e.g. V. cincinnatiensis). Multilocus sequence analysis
      of eight genes (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA and topA; concatenated
      4135 bp sequence) showed that, forming a long and independent phylogenetic
      branch, strain FJ201301T clustered with V. cincinnatiensis ATCC 35912T,
      Vibrioinjenensis KCTC 32233T and Vibriometschnikovii CIP 69.14T clearly separated
      from V. salilacus CGMCC 1.12427T. Furthermore, the highest in silico DNA-DNA
      hybridization and average nucleotide identity values between strain FJ201301T and
      the closest related species were 26.3 and 83.1 % with V. cincinnatiensis ATCC
      35912T, less than the proposed cutoff levels for species delineation, i.e. 70 and
      95 %, respectively. Biochemical, sequence and genomic analysis suggested the
      designation of strain FJ201301T representing a novel species of the genus Vibrio,
      for which the name Vibrio fujianensis sp. nov. is proposed. The type strain is
      FJ201301T (=DSM 104687T=CGMCC 1.16099T).

PMID- 29458502
TI  - Blastococcus xanthinilyticus sp. nov., isolated from monument.
AB  - A novel, non-motile, coccoid, Gram-stain-positive actinobacterium, designated BMG
      862T, was isolated from a marble sample collected from the Bulla Regia monument,
      Northern Tunisia. Its taxonomic position was determined using a polyphasic
      approach. Results from chemotaxonomic analyses showed MK-9(H4), MK-8(H4) and MK
      9(H2) as the predominant menaquinones. The major polar lipids comprised
      diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylinositol, glycophosphatidylinositol, hydroxy-phosphatidylethanolamine
      and three unidentified phospholipids. The fatty acids consisted of significant
      amounts (>=10 %) of iso-C16 : 0, C17 : 1omega8c, iso-C15 : 0 and C16 : 1omega7c.
      Phylogenetic analysis on the basis of 16S rRNA gene sequence comparisons showed
      that strain BMG 862T belongs to the genus Blastococcus, being most closely
      related to Blastococcus saxobsidens (=DSM 44509T) (99.5 %) and Blastococcus
      capsensis (=DSM 46835T=CECT 8876T) (99.3 %). The genomic DNA G+C content of the
      organism was 74.7 mol%. Results of DNA-DNA hybridization and physiological tests
      allowed differentiation of strain BMG 862T from related species. The strain was
      also characterized by its ability to hydrolyse xanthine. On the basis of
      phenotypic and molecular characteristics, strain BMG 862T (=DSM 46842T=CECT
      8884T) represents the type strain of a novel species of the genus Blastococcus,
      for which the name Blastococcus xanthinilyticus sp. nov. is proposed.

PMID- 29458503
TI  - Georgenia deserti sp. nov., a halotolerant actinobacterium isolated from a desert
      sample.
AB  - Strain SYSU D8004T was isolated from a sample collected from an arid area in
      Saudi Arabia. The isolate was Gram-stain-positive, non-motile, aerobic and non
      spore-forming. It could grow at 4-45  degrees C, at pH 6.0-10.0 and in the
      presence of up to 17 % (w/v) NaCl. Pairwise comparison of the 16S rRNA gene
      sequences indicated that strain SYSU D8004T shared highest sequence similarity
      with Georgenia halophila YIM 93316T (96.5 %). Menaquinone MK-8(H4) was detected
      as the respiratory quinone. The polar lipid profile of strain SYSU D8004T
      consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol,
      two phosphatidylinositol mannosides, two unidentified phospholipids and an
      unidentified glycolipid. Strain SYSU D8004T contained anteiso-C15 : 0, iso-C15 :
      0 and C14 : 0 as the predominant fatty acids (>10 %). Galactose, glucose and
      rhamnose were detected as whole-cell sugars. Based on analyses of the phenotypic,
      genotypic and phylogenetic characteristics, it was determined that strain SYSU
      D8004T could be differentiated from other closely related members of the genus
      Georgenia. Strain SYSU D8004T is therefore considered to represent a novel
      species of the genus Georgenia, for which the name Georgenia deserti sp. nov. is
      proposed. The type strain is SYSU D8004T (=CGMCC 1.15793T=KCTC 39987T).

PMID- 29458504
TI  - Salinisphaera aquimarina sp. nov., isolated from seawater.
AB  - A Gram-stain-negative, aerobic, rod-shaped, motile bacterium with a subpolar
      flagellum, designated strain CCMM005T, was isolated from offshore seawater at
      Qingdao, China. Phylogenetic analysis based on 16S rRNA gene sequences showed
      that strain CCMM005T belonged to the genus Salinisphaera and exhibited highest
      16S rRNA gene sequence similarity to Salinisphaera dokdonensis CL-ES53T (96.9 %).
      It showed lower sequence similarities (94.9-96.4 %) with all other
      representatives of the genus Salinisphaera. Optimal growth occurred in the
      presence of 4 % (w/v) NaCl, at 30  degrees C and at pH 7.0. The polar lipids of
      strain CCMM005T consisted of phosphatidylethanolamine, phosphatidylcholine,
      phosphatidylglycerol, one unidentified phosphoglycolipid and one unidentified
      phospholipid. The predominant isoprenoid quinone was Q-8. The major fatty acids
      were C19 : 0cyclo omega8c, C18 : 0 and C18 : 1omega7c. The DNA G+C content of
      strain CCMM005T was 65.3 mol%. On the basis of data from this polyphasic study,
      strain CCMM005T is considered to represent a novel species of the genus
      Salinisphaera, for which the name Salinisphaera aquimarina sp. nov. is proposed.
      The type strain is CCMM005T (=MCCC 1K03246T=KCTC 52640T).

PMID- 29458505
TI  - Actinotalea solisilvae sp. nov., isolated from forest soil and emended
      description of the genus Actinotalea.
AB  - A Gram-stain-positive, aerobic, non-motile and short-rod-shaped actinobacterium,
      designated THG-T121T, was isolated from forest soil. Growth occurred at 10-40 
      degrees C (optimum 28-30  degrees C), at pH 6-8 (optimum 7) and at 0-4 % NaCl
      (optimum 1 %). Based on 16S rRNA gene sequence analysis, the nearest phylogenetic
      neighbours of strain THG-T121T were identified as Actinotalea ferrariae KCTC
      29134T (97.9 %), Actinotalea fermentans KCTC 3251T (97.3 %), Cellulomonas
      carbonis KCTC 19824T (97.2 %). 16S rRNA gene sequence similarities among strain
      THG-T121T and other recognized species were lower than 97.0 %. The polar lipids
      were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two
      phosphatidylinositol mannosides, one unidentified phospholipid, three
      unidentified glycolipids and one unidentified lipid. The isoprenoid quinone was
      menaquinone (MK-10(H4)). The major fatty acids were anteiso-C15 : 0, anteiso-C15
      : 1 A, C16 : 0, iso-C16 : 0, anteiso-C17 : 0 and iso-C17 : 0. The whole-cell
      sugars of strain THG-T121T were rhamnose, ribose, mannose and glucose. The
      peptidoglycan type of strain THG-T121T is A4beta, containing l-Orn-D-Ser-L-Asp.
      The DNA G+C content of strain THG-T121T was 72.4 mol%. DNA-DNA hybridization
      values between strain THG-T121T and A. ferrariae KCTC 29134T, A. fermentans KCTC
      3251T and C. carbonis KCTC 19824T were 30.2 % (27.3 %, reciprocal analysis), 28.4
      %, (17.3 %) and 16.9 %, (9.3 %), respectively. On the basis of the phylogenetic
      analysis, chemotaxonomic data, physiological characteristics and DNA-DNA
      hybridization data, strain THG-T121T represents a novel species of the genus
      Actinotalea, for which the name Actinotaleasolisilvae sp. nov. is proposed. The
      type strain is THG-T121T (=KACC 19191T=CGMCC 4.7389T).

PMID- 29458506
TI  - Avoiding 'salami slicing' in publications describing new prokaryotic taxa.

PMID- 29458507
TI  - Parolsenella catena gen. nov., sp. nov., isolated from human faeces.
AB  - Strain 2CBEGH3T, which is an obligately anaerobic, non-pigmented, non-spore
      forming, non-motile, Gram-stain-positive coccobacillus, was isolated from a
      faecal sample of a healthy Japanese man. The 16S rRNA gene sequence analysis
      showed that strain 2CBEGH3T represented a member of the family Atopobiaceae and
      formed a monophyletic cluster with Olsenella uli DSM 7084T (93.6 % sequence
      similarity), Olsenella umbonata strain lac31T (93.0 %), Olsenella profusa JCM
      14553T (92.7 %) and Olsenella scatoligenes strain SK9K4T (92.7 %) as closest
      neighbours and Atopobium species. The hsp60 gene sequence analysis supported the
      phylogenetic relationships based on the 16S rRNA gene sequences, with sequence
      similarity values of 82.1-84.7 % to the four species described above. A unique
      three-base (one amino acid residue) insertion was found in the alignment regions
      of the hsp60 gene sequence of strain 2CBEGH3T. The major end products from d
      glucose were d- and l-lactic acids produced at the ratio of 75 : 25, while four
      species of the genus Olsenella produced d- and l-lactic acids at ratios of 94-98
      : 2-6. The isolate formed characteristic crater-like colonies on Eggerth-Gagnon
      agar plates. The major cellular fatty acids were C18 : 1omega9c, C18 : 1omega9c
      dimethyl acetal (DMA) and C16 : 0 DMA. The G+C content of the genomic DNA was
      68.4 mol%. On the basis of these data, strain 2CBEGH3T represents a novel species
      in a novel genus of the family Atopobiaceae, for which the name Parolsenella
      catena gen. nov., sp. nov. is proposed. The type strain of P. catena is 2CBEGH3T
      (=JCM 31932T=DSM 105194T).

PMID- 29458508
TI  - Rolling-circle replication initiation protein of haloarchaeal sphaerolipovirus
      SNJ1 is homologous to bacterial transposases of the IS91 family insertion
      sequences.
AB  - For most archaeal viruses, the mechanisms of genome replication are poorly
      understood, while the nature and provenance of their replication proteins are
      usually unknown. Here we show that replication of the circular double-stranded
      DNA genome of the halophilic Natrinema virus SNJ1, a member of the family
      Sphaerolipoviridae, is associated with the accumulation of single-stranded
      replicative intermediates, which is typical of rolling-circle replication. The
      homologues of RepA, the only enzyme that is indispensable for SNJ1 genome
      replication, are widespread in archaea and are most closely related to bacterial
      transposases of the IS91 and ISCR family insertion sequences, as opposed to other
      viral rolling-circle replication initiation proteins. Our results provide
      insights into the replication mechanism of archaeal viruses and emphasize the
      evolutionary connection between viruses and other types of mobile genetic
      elements.

PMID- 29458509
TI  - Emended descriptions of the species Sphingomonas adhaesiva Yabuuchi et al. 1990
      and Sphingomonas ginsenosidimutans Choi et al. 2011.
AB  - During the phylogenetic study of the genus Sphingomonas and its closely related
      genera, we found that there existed errors in the 16S rRNA gene sequence of the
      type strain of the type species of Sphingomonas adhaesiva (D13722). Data
      suggested the wrong sequence should be replaced by the sequence under the
      accession number KY927401. As the new sequence shared 99.6 % 16S rRNA gene
      sequence similarity with that of Sphingomonas ginsenosidimutans, the relationship
      between these two species was reevaluated in the present study. Analyses, based
      on the whole genome sequences, phenotypic characteristics and fatty acid profiles
      clearly show that S. adhaesiva and Sphingomonas ginsenosidimutans are two
      distinct species of the genus Sphingomonas. Considering the errors in the
      original descriptions of S. adhaesiva and S. ginsenosidimutans, we have emended
      the descriptions of the two species.

PMID- 29458510
TI  - Influence of Ambient Air Pollution on Television Use among Residents in Shanghai,
      China.
AB  - OBJECTIVES: We examined the impact of ambient air pollution on television use
      among residents in Shanghai, China. METHODS: Device-measured daily average
      duration of television use from January 2014 to December 2016 was obtained from a
      random sample of 300 households, and was matched to air pollution and weather
      data. We used an autoregressive moving-average model to estimate the association
      between air quality index (AQI) and television use. RESULTS: There was a negative
      non-linear relationship between air pollution level and television use. Compared
      to the days when air quality was good (0<=AQI<=50), days with fair air quality
      (50<AQI<=100), light air pollution (100<AQI<=150), and moderate-to-severe air
      pollution (AQI>150) were associated with a reduction in daily average television
      use by 2.9 (p = .002), 4.6 (p < .001), and 1.9 (p = .369) minutes, respectively.
      Television use decreased with daytime temperature but increased on weekend days,
      holidays, and rainy days. CONCLUSIONS: Modest but not more severe air pollution
      was associated with reduced television use. People might mitigate the detrimental
      impact of air pollution by engaging in other indoor activities and/or sleeping.

PMID- 29458511
TI  - Variability in Intensity Related to Increased Overall Bout Intensity.
AB  - OBJECTIVE: We examined the relationship between variability in self-regulated
      exercise intensity and overall intensity during acute exercise. METHODS: Overall,
      32 participants (age; 20+/-4y, body mass index (BMI) 24.1+/-3.6 kg/m2) completed
      a 30-minute self-regulated treadmill exercise bout. Participants were blinded to
      treadmill settings and adjusted speed and incline every 5-minutes as desired.
      RESULTS: Variability in exercise intensity (metabolic equivalent standard
      deviation (METSD)) was positively correlated with (r = .567, p = .001) and
      explained a significant portion of the overall exercise intensity (beta = .574, t
      = 3.713, p = .001). When accounting for physiological variables, METSD (beta =
      .381, t = 2.242, p = .034) and VO2peak (beta = .575, t = 2.864, p = .008)
      predicted overall intensity. When controlling for physiological and psychological
      variables, in addition to METSD (beta = .388), tolerance for exercise intensity
      (beta = 3.124) became a significant predictor of overall bout intensity (p <
      .05). CONCLUSIONS: In-task variability in exercise intensity was posi- tively
      related to the average intensity of the bout. Future studies should explore the
      utility of explicitly encouraging individuals to incorporate intra-bout variety
      for increasing the exercise dose while maintaining a degree of autonomy.

PMID- 29458512
TI  - Patterns and Trends of Hookah Use among New Jersey Youth: New Jersey Youth
      Tobacco Survey 2008-2014.
AB  - OBJECTIVES: In this study, the aim was to document trends of ever, past 30-day,
      and frequent (use on > 10 days/month) hookah use among New Jersey (NJ) high
      school students. METHODS: Data were analyzed from the 2008-2014 waves of the NJ
      Youth Tobacco Survey, a biennial survey of public high school students in grades
      9-12 with a mean age of 15 years. Multivariable logistic regressions assessed
      trends and correlates of hookah use. Descriptive statistics were used to
      summarize the use of cigarettes, electronic cigarettes, and other tobacco
      products (including cigars, smokeless tobacco, and bidis). RESULTS: In 2014, past
      30-day hookah use (11.8%) was as high as e-cigarette use (12.1%) and higher than
      other tobacco products. The adjusted odds of ever, past 30-day, and frequent
      hookah use were significantly higher in 2014 than 2008. Past 30-day hookah use
      was more common among users of other tobacco products. CONCLUSIONS: Effective
      strategies have been used in cigarette tobacco control, and cigarette consumption
      has decreased as a result. Similar strategies should be employed to encompass
      emerging tobacco products, with necessary modifications to reduce the prevalence
      of all tobacco use among youth.

PMID- 29458513
TI  - Adapting a Skin Cancer Prevention Intervention for Multiethnic Adolescents.
AB  - OBJECTIVE: We tested the effectiveness of a school-based skin cancer prevention
      intervention entitled "SunSafe in the Middle School Years" adapted for
      multiethnic high school students. METHODS: In Hawai'i, 208 10th graders (51.6%
      Asian, 30.4% Native Hawaiian/Pacific Islander, 8.4% white, 3.5% Hispanic, 2.7%
      black) participated. Changes in sun protection knowledge, attitudes, and self
      reported behaviors were measured using a standardized 18-item survey. The
      Systematic Observation of Sun Protection Factors (SOSPF) instrument assessed
      aggregate sun protection behaviors. RESULTS: At posttest, improvements were found
      in 13 of 18 survey items (p < .05), and retained in 10 items at 12-months
      following baseline assessments; sun-protection attitudes and intended tanning
      behavior did not show improvement. Six observers using SOSPF reliably measured
      students' sun protection behaviors at school including use of hats, sunglasses,
      long sleeves, lower body coverage, and shade (ICC > .77). CONCLUSIONS: We
      uncovered a lack of knowledge about UVR exposure, tanning, and lifetime skin
      cancer risk among multiethnic high school students. We found that students'
      tanning attitudes may be influenced by self-perceptions regarding their own
      complexion, but were willing to modify their sun protection behaviors once
      informed about skin cancer risk.

PMID- 29458514
TI  - Caregiver Daily Experiences Associated with Child Asthma Symptoms.
AB  - OBJECTIVE: In this study, we used ecological momentary assessment (EMA) delivered
      via smart- phones to determine how the daily experiences (comfort in
      neighborhood, ability to manage child's asthma, positive/negative affect) of 59
      caregivers (90% African-American/black) living in an urban setting are associated
      with asthma symptoms in children ages 7-12 years (M = 9.56 years). METHODS:
      Caregivers and their children with asthma completed a baseline research ses-
      sion, followed by 14 days of EMA surveys completed on smartphones. EMA enables
      researchers to examine within-person processes while preserving the ecological
      validity of the data and re- ducing retrospective recall bias. RESULTS: On days
      when caregivers reported more child asthma symptoms, they also reported feeling
      less comfortable in their neighborhoods and less able to control their child's
      asthma at home. Baseline reports of caregiver quality of life were also associ-
      ated with child asthma symptoms. CONCLUSIONS: Findings highlight the need for
      researchers and clinicians to recognize that both asthma (ie, ability to control
      asthma) and non-asthma related factors (ie, factors related to neighborhoods) may
      be associated with caregivers' perceptions of their children's asthma symptoms.
      Perceptions of child symptoms have important consequences for daily asthma care,
      including decisions related to healthcare utilization.

PMID- 29458515
TI  - A Pilot Feasibility Study to Improve Food Parenting Practices.
AB  - OBJECTIVES: We examined the feasibility and acceptability of a novel home-based
      intervention to improve the food parenting practices of low-income mothers with
      preschool-aged children. METHODS: Mother-child dyads (N = 15) were recruited from
      WIC in southern Rhode Island. A non-experimental, pretest-posttest design was
      used to assess changes in maternal food parenting practices. Dyads participated
      in 3 home-based sessions that included baseline measures and an evening meal
      video recording at session 1, a motivational interviewing (MI) intervention that
      included feedback on the evening meal video recording at session 2, and a
      satisfaction ques- tionnaire at session 3. Pretest-posttest measures included 5
      subscales of the Comprehensive Feeding Practices Questionnaire. RESULTS: Fifteen
      mother-child dyads (mothers: 32.3, SD = 4.6 years, 86.7% white; children: 3.2, SD
      = 0.9 years, male = 73.3%, 66.7% white) completed the study. Mothers reported
      improvements in food parenting practices following the home-based MI
      intervention. Overall, 93% of mothers 'strongly agreed' that it was worth their
      effort to participate in the study. CONCLUSIONS: A home-based MI intervention may
      be an effective strategy for improving maternal food parenting practices in low
      income populations. Most mothers found that watching themselves was informative
      and applicable to their own lives.

PMID- 29458516
TI  - Chronic Disease Risk Typologies among Young Adults in Community College.
AB  - OBJECTIVES: To address chronic disease risk holistically from a behavioral
      perspective, insights are needed to refine understanding of the covariance of key
      health behaviors. This study aims to identify distinct typologies of young adults
      based on 4 modifiable risk factors of chronic disease using a latent class
      analysis approach, and to describe patterns of class membership based on
      demographic characteristics, living arrangements, and weight. METHODS: Overall,
      441 young adults aged 18-35 attending community colleges in the Minnesota Twin
      Cities area completed a baseline questionnaire for the Choosing Healthy Options
      in College Environments and Settings study, a RCT. Behavioral items were used to
      create indicators for latent classes, and individuals were classified using
      maximum-probability assignment. RESULTS: Three latent classes were identified:
      'active, binge-drinkers with a healthy dietary intake' (13.1%); 'non-active,
      moderate-smokers and non-drinkers with poor dietary intake' (38.2%); 'moderately
      active, non-smokers and non-drinkers with moderately healthy dietary intake'
      (48.7%). Classes exhibited unique demographic and weight-related profiles.
      CONCLUSIONS: This study may contribute to the literature on health behaviors
      among young adults and provides evidence that there are weight and age
      differences among subgroups. Understanding how behaviors cluster is important for
      identifying groups for targeted interventions in community colleges.

PMID- 29458517
TI  - Effects of Large Cigarette Warning Labels on Smokers' Expected Longevity.
AB  - OBJECTIVES: Smokers underestimate the health risks of smoking and overestimate
      their expected longevity. Warning labels on cigarette packs might help correct
      these misperceptions. METHODS: We carried out an online study with 1200 smokers
      (18-62 years old), randomized to 3 conditions: text warning labels, pictorial
      warning labels, and a control group (water bottle labels). Warning labels were
      based on those proposed by the US Food and Drug Administration in 2010.
      Participants in each condition saw 4 randomly selected labels and rated their
      expected longevity and chances of surviving to age 75 after exposure. Analyses of
      covariance controlled for cigarettes per day and self-rated health. RESULTS:
      Compared to control, both text and pictorial warnings reduced participants'
      expected longevity (text: mean = 76.8 years, pictorial: 77.3, control 79.4) and
      their estimated chances of living to 75 (text: 62.0%, pictorial: 63.0%, control
      66.5%). The contrast between text and pictorial labels combined and control
      showed significantly reduced expected longevity (p = .011) and chances of living
      to 75 (p = .004). Differences between text and pictorial conditions were not
      statistically significant. CONCLUSIONS: Large text or pictorial warnings on
      cigarette packs might help smokers develop a more accurate understanding of the
      effects of smoking on their longevity.

PMID- 29458518
TI  - Perceived Stress Predicts Lower Physical Activity in African-American Boys, but
      not Girls.
AB  - OBJECTIVES: The purpose of this study was to examine cross-sectional
      relationships of psychological stress, stress coping, and minutes of moderate-to
      vigorous physical activity (MVPA) in Amer- ican-American (AA) boys and girls.
      METHODS: A community-based sample of 139 AA adolescents (mean age 14.7 years; SD
      = 1.8 years; 64.7% girls; 30% obese) from Washtenaw County, Michigan was included
      in this analysis. Psychological stress was assessed using the Daily Stress
      Inventory and the Perceived Stress Scale. Coping strategies were evaluated using
      the Schoolager's Coping Strategies questionnaire. Physical activity was measured
      objectively via accelerometry. RESULTS: Compared to boys, girls participated in
      approximately 13 fewer minutes of MVPA (p < .001) per day and reported
      significantly higher levels of daily stress (p = .03) and perceived stress (p <
      .001). In addition, girls reported using a greater number of coping strategies (p
      = .01) at a greater frequency (p = .04) compared to boys. However, perceived
      stress significantly predicted lower levels of MVPA (p = .03) in boys only.
      CONCLUSIONS: There are important gender differences in how AA girls perceive,
      experience, and cope with stress compared to AA boys. Although AA girls reported
      higher levels of stress and employed more coping strategies, perceived stress was
      associated with physical inactivity in AA boys, but not girls. Additional
      research is warranted to better understand the influence of stress on the choice
      to be physically active in AA youth.

PMID- 29458519
TI  - Intrapersonal Factors of Male and Female Adolescent Fruit and Vegetable Intake.
AB  - OBJECTIVES: In this study, we examined the role of socio-demographic
      (race/ethnicity, sex, grade, nativity, literacy, body mass index) and individual
      level (normative beliefs, knowledge, perceived barriers, food preference, self
      efficacy) factors on US adolescent fruit and vegetable consumption. METHODS: We
      conducted hierarchical multiple regression analysis to determine the influence of
      factors on adolescent fruit and vegetable consumption in a nationally represen-
      tative sample of 795 adolescents from the National Cancer Institute's 2014 Family
      Life, Activity, Sun, Health, and Eating (FLASHE) study. RESULTS: Socio
      demographic variables explained little variance (1.7%) whereas individual-level
      factors explained approximately 29% of the variance in adolescent fruit and
      vegetable consumption. Statistically significant (p < .001) predictors of
      adolescent fruit and vegetable consumption were food preference (beta = .253),
      self-efficacy (beta = .184), perceived barriers (beta = -.139), and normative
      beliefs (beta = .134). After controlling for sex, food preference and normative
      beliefs were stronger predictors of male, and perceived barriers was a stronger
      predictor of female, adolescent fruit and vegetable consumption. CONCLUSIONS:
      Understanding the predictive strength and sex-specific differences of
      intrapersonal variables on male and female adolescent fruit and vegetable
      consumption informs health promotion efforts to increase intake to recommended
      amounts.

PMID- 29458521
TI  - Two novel thermally resistant endolysins encoded by pseudo T-even bacteriophages
      RB43 and RB49.
AB  - Identification and cloning of genes as well as biochemical characterization of
      the gene products were carried out for two novel endolysins of pseudo T-even
      lytic bacteriophages RB43 and RB49, which represent different myovirus groups of
      the subfamily Tevenvirinae. Genes RB43ORF159c and RB49r102 were cloned in E. coli
      cells, and their products were purified to electrophoretic homogeneity with an up
      to 80 % yield of total activity. In respect to substrate specificity, both
      enzymes were found to be lytic l-alanoyl-d-glutamate peptidases belonging to the
      M15 family. The pH optimum functioning of both endolysins was within the range
      7.0-9.0, whereas the optimal values of ionic strength were different for the two
      proteins (25 mM vs 100 mM for the RB43 and RB49 endolysins respectively). Both
      peptidases were thermally resistant, with the RB43 endolysin being more stable
      (it restored 81 % of enzyme activity and 96 % of secondary structure after a 10
      min heating at 90  degrees C) than its RB49 counterpart (27 and 77%
      respectively). The possible origin of genes of lytic l-alanoyl-d-glutamate
      peptidases of myoviruses as a result of horizontal transfer in the variable parts
      of genomes between unrelated phages having a common host is discussed.

PMID- 29458520
TI  - Social Media Use and Depression and Anxiety Symptoms: A Cluster Analysis.
AB  - OBJECTIVES: Individuals use social media with varying quantity, emotional, and
      behavioral at- tachment that may have differential associations with mental
      health outcomes. In this study, we sought to identify distinct patterns of social
      media use (SMU) and to assess associations between those patterns and depression
      and anxiety symptoms. METHODS: In October 2014, a nationally-representative
      sample of 1730 US adults ages 19 to 32 completed an online survey. Cluster
      analysis was used to identify patterns of SMU. Depression and anxiety were
      measured using respective 4-item Patient-Reported Outcome Measurement Information
      System (PROMIS) scales. Multivariable logistic regression models were used to
      assess associations between clus- ter membership and depression and anxiety.
      RESULTS: Cluster analysis yielded a 5-cluster solu- tion. Participants were
      characterized as "Wired," "Connected," "Diffuse Dabblers," "Concentrated
      Dabblers," and "Unplugged." Membership in 2 clusters - "Wired" and "Connected" -
      increased the odds of elevated depression and anxiety symptoms (AOR = 2.7, 95% CI
      = 1.5-4.7; AOR = 3.7, 95% CI = 2.1-6.5, respectively, and AOR = 2.0, 95% CI = 1.3
      3.2; AOR = 2.0, 95% CI = 1.3-3.1, respectively). CONCLUSIONS: SMU pattern
      characterization of a large population suggests 2 pat- terns are associated with
      risk for depression and anxiety. Developing educational interventions that
      address use patterns rather than single aspects of SMU (eg, quantity) would
      likely be useful.

PMID- 29458522
TI  - Paenibacillus mobilis sp. nov., a Gram-stain-negative bacterium isolated from
      soil.
AB  - A novel Gram-stain-negative bacterium, designated strain S8T, was isolated from a
      soil sample obtained in Gyeonggi Province, Republic of Korea. Cells of strain S8T
      were endospore-forming, motile by means of peritrichous flagella, and rod-shaped.
      S8T colonies were round, convex, wavy and white. Strain S8T grew optimally at 37 
      degrees C, pH 6-8, and up to 2.0 % (w/v) NaCl. Based on 16S rRNA gene sequence
      similarity, strain S8T was affiliated with the genus Paenibacillus in the family
      Paenibacillaceae and was most closely related to Paenibacillus yonginensis DCY84T
      and Paenibacillus physcomitrellae XBT (98.8 and 97.1 % sequence similarity). The
      DNA G+C content of the novel strain was 53.1+/-0.3 mol%. Strain S8T contained
      diphosphatidylglycerol, phosphatidylglycerol, two phospholipids, four
      aminophospholipids, an aminolipid and three unidentified lipids. The major fatty
      acid was anteiso-branched C15 : 0. The quinone was menaquinone MK-7. The
      peptidoglycan of strain S8T contained meso-diaminopimelic acid. The DNA-DNA
      hybridization values of strain S8T with P. yonginensis KCTC 33428T and P.
      physcomitrellae DSM 29851T were 44 % and 32 %, respectively. Data from the DNA
      DNA hybridization, biochemical, phylogenetic and physiological analyses indicate
      that strain S8T (=KCTC 33848T=JCM 31672T) represents a novel species of the genus
      Paenibacillus, for which the name Paenibacillus mobilis sp. nov. is proposed.

PMID- 29458523
TI  - hnRNP G prevents inclusion on the HPV16 L1 mRNAs of the central exon between
      splice sites SA3358 and SD3632.
AB  - HPV16 late L1 mRNAs encode a short central exon that is located between HPV16 3'
      splice site SA3358 and HPV16 5'-splice site SD3632. While SA3358 is used to
      produce both HPV16 early mRNAs encoding the E6 and E7 oncogenes, and late mRNAs
      encoding E4, L1 and L2, SD3632 is used exclusively to produce late L1 mRNA. We
      have previously identified an 8-nucleotide regulatory RNA element that is
      required for inclusion of the exon between SA3358 and SD3632 to produce L1 mRNAs
      at the expense of mRNAs polyadenylated at the HPV16 early polyadenylation signal
      pAE. Here we show that this HPV16 8-nucleotide splicing enhancer interacts with
      hnRNP G. Binding of hnRNP G to this element prevents inclusion of the exon
      between SA3358 and SD3632 on the HPV16 late L1 mRNAs. We concluded that hnRNP G
      has a splicing inhibitory role and that hnRNP G can control HPV16 mRNA splicing.

PMID- 29458524
TI  - IFN and cytokine responses in ducks to genetically similar H5N1 influenza A
      viruses of varying pathogenicity.
AB  - Ducks, the reservoir host, are generally permissive to influenza A virus
      infection without disease symptoms. This natural ecology was upset by the
      emergence of H5N1 strains, which can kill ducks. To better understand host-virus
      interactions in the reservoir host, and influenza strain-specific molecular
      contributions to virulence, we infected White Pekin ducks with three similar H5N1
      viruses, with known differences in pathogenicity and replication rate. We
      quantified viral replication and innate immune gene activation by qPCR, in lung
      and spleen tissues, isolated on each of the first 3 days of infection. The three
      viruses replicated well, as measured by accumulation of matrix gene transcript,
      and viral load declined over time in the spleen. The ducks produced rapid, but
      temporally limited, IFN and cytokine responses, peaking on the first day post
      infection. IFN and proinflammatory cytokine gene induction were greater in
      response to infection with the more lethal viruses, compared to an attenuated
      strain. We conclude that a well-regulated IFN response, with the ability to
      overcome early viral immune inhibition, without hyperinflammation, contributes to
      the ability of ducks to survive H5N1 influenza replication in their airways, and
      yet clear systemic infection and limit disease.

PMID- 29458525
TI  - Major histocompatibility complex I of swine respiratory cells presents conserved
      regions of influenza proteins.
AB  - Influenza A virus in swine (IAV-S) is a prevalent respiratory pathogen in pigs
      that has deleterious consequences to animal and human health. Pigs represent an
      important reservoir for influenza and potential mixing vessel for novel gene
      reassortments. Despite the central role of pigs in recent influenza outbreaks,
      much remains unknown about the impact of swine immunity on IAV-S transmission,
      pathogenesis, and evolution. An incomplete understanding of interactions between
      the porcine immune system and IAV-S has hindered development of new diagnostic
      tools and vaccines. In order to address this gap in knowledge, we identified
      swine leukocyte antigen (SLA) restricted IAV-S peptides presented by porcine
      airway epithelial cells using an immunoproteomics approach. The majority of MHC
      associated peptides belonged to matrix 1, nucleoprotein and nonstructural 1
      proteins. Future investigation of the potential cross-reactive nature of these
      peptides is needed to confirm antigen recognition by cytotoxic T lymphocytes and
      their utility as vaccine candidates.

PMID- 29458526
TI  - Identification of a novel linear B-cell epitope as a vaccine candidate in the
      N2N3 subdomain of Staphylococcus aureus fibronectin-binding protein A.
AB  - PURPOSE: To explore an epitope-based vaccine against Staphylococcus aureus, we
      screened the epitopes in the N2N3 subdomain of fibronectin-binding protein A
      (FnBPA) as a surface component of S. aureus. METHODOLOGY: We expressed N2N3
      proteins and prepared monoclonal antibodies (mAbs) against N2N3 by the hybridoma
      technique, before screening the B-cell epitopes in N2N3 using a phage-displayed
      random 12-mer peptide library with these mAbs against N2N3. Finally, we analysed
      the characters of the screened epitopes using immunofluorescence and an S. aureus
      infection assay. RESULTS: In this paper, we identified a linear B-cell epitope in
      N2N3 through screening a phage-displayed peptide library with a 3C3 mAb against
      the N2N3. The 3C3 mAb recognized the 159IETFNKANNRFSH171 sequence of the N2N3
      subdomain. Subsequently, site-directed mutagenic analysis demonstrated that
      residues F162, K164, N167, R168 and F169 formed the core of 159IETFNKANNRFSH171,
      and this core motif was the minimal determinant of the B-cell epitope recognized
      by the 3C3 mAb. The epitope 159IETFNKANNRFSH171 showed high homology among
      different S. aureus strains. Moreover, this epitope was exposed on the surface of
      the S. aureus by using an enzyme-linked immunosorbent assay (ELISA) assay and an
      indirect immunofluorescence assay. As expected, the epitope peptide evoked a
      protective immune response against S. aureus infection in immunized mice.
      CONCLUSION: We identified a novel linear B-cell epitope, 159IETFNKANNRFSH171, in
      the N2N3 subdomain of S. aureus fibronectin-binding protein A that is recognized
      by 3C3 mAb, which will contribute to the further study of an epitope-based
      vaccine candidate against S. aureus.

PMID- 29458528
TI  - A point-mutation of Coleus blumei viroid 1 switches the potential to transmit
      through seed.
AB  - Viroids are highly structured, single-stranded, non-protein-coding circular RNA
      pathogens that replicate, spread and elicit severe to mild disease symptoms in
      sensitive host species. The functions of viroids are thought to be due to a
      molecular element (or elements) embedded within the small RNA molecule that
      recruits the host factors responsible for transcription, RNA transportation and
      regulation of gene expression. Coleus blumei viroid 1 (CbVd-1) is distributed
      worldwide and is known for its characteristic property of having an extremely
      high frequency of seed transmission. During our analysis of CbVd-1 seed
      transmission, two variants, CbVd-1/25A and CbVd-1/25UU, were shown to have
      distinct seed-transmission frequencies: 30 and 0 %, respectively. Seven
      infectious dimeric forms of CbVd-1 cDNA clones were created based on the
      sequences of CbVd-1/25A,CbVd-1/25UU and an additional five variants with unique
      loop structures in other portion(s) of the molecule, and in vitro transcripts
      were inoculated into viroid-free coleus seedlings. All seven CbVd-1 variants
      showed infectivity. Nucleotide sequence analysis of the progeny revealed that
      four of the five additional mutants changed to either CbVd-1/25A or CbVd-1/25UU,
      while, CbVd-1/25A, CbVd-1/25UU and one of the five additional mutants (CbVd-1/I2)
      replicated stably. As expected, CbVd-1/25A and CbVd-1/I2 were transmitted through
      seeds, but CbVd-1/25UU was not. CbVd-1/25A and CbVd-1/I2 shared the same
      nucleotide at position 25 in loop five but are different from CbVd-1/25UU at that
      position. Therefore, nucleotide 25 in loop five was identified as a determinant
      for seed transmission of CbVd-1.

PMID- 29458527
TI  - Terrimonas soli sp. nov., isolated from farmland soil.
AB  - A Gram-staining-negative, aerobic, non-motile and rod-shaped bacterium that
      produced yellow viscous colonies, designated FL-8T, was isolated from farmland
      soil in Chuzhou, Anhui province, PR China. 16S rRNA gene sequence similarities
      between strain FL-8T and the type strains of species of the genus Terrimonas with
      validly published names ranged from 94.6 to 96.1 %. Strain FL-8T contained iso
      C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH as the predominant fatty acids. The
      predominant polar lipid of strain FL-8T was phosphatidylethanolamine. The sole
      respiratory quinone of strain FL-8T was MK-7 and the DNA G+C content was 44.8
      mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain FL
      8T is considered to represent a novel species of the genus Terrimonas, for which
      the name Terrimonassoli sp. nov. is proposed. The type strain is FL-8T (=CCTCC AB
      2017059T=JCM 32095T).

PMID- 29458529
TI  - Both murine host and inoculum modulate expression of experimental variant
      Creutzfeldt-Jakob disease.
AB  - Transmissible spongiform encephalopathies (TSEs) are infections that are
      experimentally transmissible to laboratory animals. TSE agents (prions) can be
      serially passaged in the same animal species. The susceptibility of mice to
      infection with specific TSE agents can be unpredictable and must be established
      empirically. We challenged wild-type C57BL/6 and RIIIS/J mice and transgenic mice
      overexpressing bovine prion protein (TgBo110) with a human brain infected with
      variant Creutzfeldt-Jakob disease (vCJD) agent and pooled brains of macaques
      experimentally infected with human vCJD agent (first-passage macaque vCJD). The
      human vCJD brain yielded a wide range of infectivity titres in different mouse
      models; TgBo110 mice were the most sensitive. In contrast, infectivity titres of
      macaque vCJD brain were similar in all three murine models. The brains of RIIIS/J
      mice infected with both human and macaque vCJD had mild or no vacuolation, while
      infected C57BL/6 and TgBo110 mice had spongiform degeneration with vacuolation.
      Abnormal prion protein (PrPTSE) extracted from the brains of vCJD-infected
      TgBo110 mice displayed different glycosylation profiles and had greater
      resistance to denaturation by guanidine hydrochloride than PrPTSE from infected
      wild-type mice or from either inoculum. Those histopathological features of TSE
      and physical properties of PrPTSE in mice with experimental vCJD were intrinsic
      to the host, even though we also observed differences between wild-type mice
      infected with either agent, suggesting a modulatory effect of the inoculum. This
      study compared three widely used mouse models infected with two different vCJD
      inocula. The results show that the host plays a major role in manifestations of
      experimental TSEs.

PMID- 29458530
TI  - SUMOylation of IE2p86 is required for efficient autorepression of the human
      cytomegalovirus major immediate-early promoter.
AB  - The human cytomegalovirus (HCMV) IE2p86 protein is pivotal for coordinated
      regulation of viral gene expression. Besides functioning as a promiscuous
      transactivator, IE2p86 is also known to negatively regulate its own
      transcription. This occurs via direct binding of IE2p86 to a 14-bp palindromic
      DNA element located between the TATA box and the transcription start site of the
      major immediate-early promoter (MIEP), which is referred to as the cis repression
      signal (CRS). However, the exact mechanism of IE2p86-based autorepression is
      still unclear. By testing a series of IE2p86 mutants in transient expression
      assays, we found that not only did a DNA binding-deficient mutant of IE2p86 fail
      to repress the MIEP, but SUMOylation-negative mutants also failed to repress it.
      This finding was further supported by infection studies with primary fibroblasts
      harbouring a MIEP-driven transgene as a reporter. Here, we observed that a
      recombinant HCMV expressing SUMOylation-negative IE2p86 was defective in
      transgene downregulation, in contrast to wild-type HCMV. Interestingly, however,
      a double-mutant virus in which both the SUMO acceptor sites and the SUMO
      interaction motif (SIM) of IE2p86 were inactivated regained the ability to
      silence the MIEP. This correlated with increased expression levels of the IE2
      isoforms IE2p40 and IE2p60, suggesting that these late proteins may contribute to
      MIEP suppression, thus compensating for the loss of IE2p86 SUMOylation. In
      summary, our results show that autorepression of the MIEP is not only regulated
      by late isoforms of IE2, but also depends on posttranslational SUMO modification,
      revealing a novel mechanism to fine-tune the expression of this important viral
      gene region.

PMID- 29458531
TI  - Adhaeribacter swui sp. nov., isolated from wet mud.
AB  - Strain 17mud1-7T, a pink, aerobic, catalase-positive, oxidase-positive and Gram
      reaction-negative bacterium, was isolated from wet mud. The isolate grew
      aerobically at 18-37  degrees C (optimum 28  degrees C), at pH 6.0-8.0 (optimum
      pH 7.0) and in the presence of 0-1 % (w/v) NaCl (optimum 0 % NaCl). Phylogenetic
      analysis based on 16S rRNA gene sequences indicated that strain 17mud1-7T
      belonged to the genus Adhaeribacter with highest sequence similarity of 96.4 % to
      Adhaeribacter aerophilus 6424S-25T. The strain showed the typical chemotaxonomic
      characteristics of the genus Adhaeribacter, with the presence of menaquinone MK-7
      as the respiratory quinone, and summed feature 4 (composed of iso-C17 : 1
      I/anteiso-C17 : 1 B), iso-C15 : 0 and C16 : 1omega5c as the major fatty acids
      are. The polar lipid profile contained two aminophosphoglycolipids, two
      glycolipids and three unidentified lipids. The DNA G+C content of strain 17mud1
      7T was 45.9 mol%. Strain 17mud1-7T should thus be classified as representing a
      novel species in the genus Adhaeribacter, for which the name Adhaeribacter swui
      sp. nov. is proposed. The type strain is 17mud1-7T (=KCTC 52873T=NBRC 112824T).

PMID- 29458532
TI  - ICTV Virus Taxonomy Profile: Ampullaviridae.
AB  - The family Ampullaviridae includes viruses with linear dsDNA genomes that
      replicate in hyperthermophilic archaea from the genus Acidianus. The virions have
      a unique champagne bottle-shaped morphology and consist of a nucleoprotein
      filament condensed into a cone-shaped core, which is encased by an envelope, with
      the base of the 'bottle' decorated with a ring of 20 filaments. Genome
      replication is presumably carried out by the virus-encoded protein-primed family
      B DNA polymerase. The bottle-shaped morphology is unprecedented among viruses of
      bacteria and eukaryotes and represents a group of archaea-specific virion
      morphotypes. This is a summary of the International Committee on Taxonomy of
      Viruses (ICTV) Report on the taxonomy of the Ampullaviridae, which is available
      at www.ictv.global/report/ampullaviridae.

PMID- 29458533
TI  - A clash of ideas - the varying uses of the 'species' term in virology and their
      utility for classifying viruses in metagenomic datasets.
AB  - Species definitions of viruses are frequently descriptive, with assignments often
      being based on their disease manifestations, host range, geographical
      distribution and transmission routes. This method of categorizing viruses has
      recently been challenged by technology advances, such as high-throughput
      sequencing. These have dramatically increased knowledge of viral diversity in the
      wider environment that dwarfs the current catalogue of viruses classified by the
      International Committee for the Taxonomy of Viruses (ICTV). However, because such
      viruses are known only from their sequences without phenotypic information, it is
      unclear how they might be classified consistently with much of the existing
      taxonomy framework. This difficulty exposes deeper incompatibilities in how
      species are conceptualized. The original species assignments based on disease or
      other biological attributes were primarily descriptive, similar to principles
      used elsewhere in biology for species taxonomies. In contrast, purely sequence
      based classifications rely on genetic metrics such as divergence thresholds that
      include or exclude viruses in individual species categories. These different
      approaches bring different preconceptions about the nature of a virus species,
      the former being more easily conceptualized as a category with a part/whole
      relationship of individuals and species, while species defined by divergence
      thresholds or other genetic metrics are essentially logically defined groups with
      specific inclusion and exclusion criteria. While descriptive species definitions
      match our intuitive division of viruses into natural kinds, rules-based genetic
      classifications are required for viruses known from sequence alone, whose
      incorporation into the ICTV taxonomy is essential if it is to represent the true
      diversity of viruses in nature.

PMID- 29458534
TI  - Specific transcriptional and post-transcriptional regulation of the major
      immediate early ICP4 gene of GaHV-2 during the lytic, latent and reactivation
      phases.
AB  - Transcriptional and post-transcriptional mechanisms are involved in the switch
      between the lytic, latent and reactivation phases of the viral cycle in
      herpesviruses. During the productive phases, herpesvirus gene expression is
      characterized by a temporally regulated cascade of immediate early (IE), early
      (E) and late (L) genes. In alphaherpesviruses, the major product of the IE ICP4
      gene is a transcriptional regulator that initiates the cascade of gene expression
      that is essential for viral replication. In this study, we redefine the infected
      cell protein 4 (ICP4) gene of the oncogenic Marek's disease virus (MDV or gallid
      herpesvirus 2) as a 9438 nt gene ended with four alternative poly(A) signals and
      controlled by two alternative promoters containing essentially ubiquitous
      functional response elements (GC, TATA and CCAAT boxes). The distal promoter is
      associated with ICP4 gene expression during the lytic and the latent phases,
      whereas the proximal promoter is associated with the expression of this gene
      during the reactivation phase. Both promoters are regulated by DNA methylation
      during the viral cycle and are hypermethylated during latency. Transcript
      analyses showed ICP4 to consist of three exons and two introns, the alternative
      splicing of which is associated with five predicted nested ICP4ORFs. We show that
      the ICP4 gene is highly and specifically regulated by transcriptional and post
      transcriptional mechanisms during the three phases of the GaHV-2 viral cycle,
      with a clear difference in expression between the lytic phase and reactivation
      from latency in our model.

PMID- 29458535
TI  - Isolation, characterization and genomic analysis of a novel lytic bacteriophage
      vB_SsoS-ISF002 infecting Shigella sonnei and Shigella flexneri.
AB  - PURPOSE: Shigellosis is one of the most important food-borne and water-borne
      diseases worldwide. Although antibiotics are considered as efficient agents for
      shigellosis treatment, improper use of these has led to the emergence of
      antibiotic-resistant Shigella spp. Therefore, finding a new strategy as
      alternative treatment seems necessary. METHODOLOGY: Different samples from a
      wastewater treatment plant were used to isolate Shigella spp. specific phages.
      Physiological properties were determined, and genomic analysis was also carried
      out. RESULTS: A virulent Siphoviridae bacteriophage, vB_SsoS-ISF002, was isolated
      from urban wastewater in Iran and showed infectivity to different isolates of
      both Shigella sonnei and Shigella flexneri. vB_SsoS-ISF002 was stable at
      different pH values and temperatures. It had a short latent period (15 min), a
      large burst size (76+/-9 p.f.u. cell-1) and appropriate lytic activity especially
      at high MOI. Its genome (dsDNA) was 50 564 bp with 45.53 % GC content and 76
      predicted open reading frames. According to comparative genomic analysis and
      phylogenic tree construction, vB_SsoS-ISF002 was considered as a member of the
      T1virus genus. CONCLUSION: These results indicated that vB_SsoS-ISF002 is a novel
      virulent T1virus phage and may have potential as an alternative treatment for
      shigellosis.

PMID- 29458536
TI  - Phyllobacterium salinisoli sp. nov., isolated from a Lotus lancerottensis root
      nodule in saline soil from Lanzarote.
AB  - A Gram-negative rod, designated strain LLAN61T, was isolated from a root nodule
      of Lotus lancerottensis growing in a saline soil sample from Lanzarote (Canary
      Islands). The strain grew optimally at 0.5 % (w/v) NaCl and tolerated up to 3.5
      %. The 16S rRNA gene sequence analysis showed that strain LLAN61T belonged to
      genus Phyllobacterium and that Phyllobacteriumleguminum ORS 1419T and
      Phyllobacteriummyrsinacearum IAM 13584T are the closest related species with
      97.93 and 97.86% similarity values, respectively. In the atpD phylogeny, P.
      leguminum ORS 1419T and P. myrsinacearum ATCC 43591T, sharing similarities of
      87.6 and 85.8% respectively, were also the closest species to strain LLAN61T. DNA
      DNA hybridization showed an average value of 21 % between strain LLAN61T and P.
      leguminum LMG 22833T, and 6 % with P. myrsinacearum ATCC 43590T. The predominant
      fatty acids were C19 : 0 cyclo omega8c and C18 : 1omega6c/C18 : 1omega7c (summed
      feature 8). The DNA G+C content was 58.0 mol%. Strain LLAN61T differed from its
      closest relatives in some culture conditions and in assimilation of several
      carbon sources. Based upon the results of phylogeny, DNA-DNA hybridization,
      phenotypic tests and fatty acid analysis, this strain should be classified as a
      novel species of Phyllobacterium for which the name Phyllobacterium salinisoli
      sp. nov. is proposed (type strain LLAN61T=LMG 30173T = CECT 9417T).

PMID- 29458537
TI  - Desulfothermobacter acidiphilus gen. nov., sp. nov., a thermoacidophilic sulfate
      reducing bacterium isolated from a terrestrial hot spring.
AB  - An anaerobic sulfate-reducing micro-organism, strain 3408-1T, was isolated from a
      terrestrial hot spring in Kamchatka peninsula (Russia). The cells were spore
      forming rods with a Gram-positive type of cell wall. The new isolate was a
      moderately thermoacidophilic anaerobe able to grow either by sulfate or
      thiosulfate respiration with H2 or formate as substrates, or by fermenting yeast
      extract, maltose, sucrose, glucose and pyruvate. The fermentation products were
      acetate, CO2 and H2. The pH range for growth was 2.9-6.5, with an optimum at 4.5.
      The temperature range for growth was 42-70  degrees C, with an optimum at 55 
      degrees C. The G+C content of DNA was 58 mol%. Phylogenetic analysis of the 16S
      rRNA gene showed that strain 3408-1T belongs to the family
      Thermoanaerobacteraceae, order Thermoanaerobacterales and was distantly related
      to the species of the genus Ammonifex(93-94 % sequence similarity). On the basis
      of physiological properties and results of phylogenetic analysis, strain 3408-1T
      is considered to represent a novel species of a new genus, for which the name
      Desulfothermobacter acidiphilus gen. nov., sp. nov. is proposed. The type strain
      is 3408-1T (=DSM 105356T=VKM B-3183T).

PMID- 29458538
TI  - The double adjuvants LTB and CpG significantly enhanced the immuno-protective
      effects of recombinant GIT derived from Staphylococcus aureus and Streptococcus
      in mice.
AB  - PURPOSE: In this study, we prepared GapC1-150-IsdB126-361-TRAP (GIT) proteins
      plus heat-labile enterotoxin B (LTB) as an intra-molecular adjuvant, together
      with CpG to further enhance its immunogenicity. METHODOLOGY: Initially, the
      target genes were acquired and inserted into pET-32a (+) vectors to express LTB
      GIT protein. LTB-GIT expression was confirmed by Western blotting and its
      immunocompetence was estimated through ELISA. Further, we immunized BALB/c mice
      with the LTB-GIT plus CpG adjuvant. After the second immunization, the antigen
      specific CD4+ cell responses for IFN-gamma, IL-2, IL-4 and IL-10 were monitored
      by intracellular cytokine staining (ICS) assay. After the third immunization, the
      level of IgG antibodies in the serum from immunized groups was assessed by ELISA,
      and the protective immune response was appraised by Staphylococcus aureus and
      Streptococcus dysgalactiae challenge. RESULTS: The ELISA results showed that the
      OD450nm value of the LTB-GIT group was significantly higher than that of the BSA
      group. The group immunized with LTB-GIT plus CpG exhibited significantly stronger
      CD4+ T cell responses for IFN-gamma, IL-2, IL-4 and IL-10 compared to the group
      immunized with LTB-GIT, GIT alone orLTB-GIT plus CpG. In addition, the group
      immunized with LTB-GIT plus CpG generated the highest level of IgG antibodies
      against GIT among all of the groups, and our results also showed that LTB-GIT
      plus CpG markedly improved the survival percentage of mice compared to other
      groups. CONCLUSION: We confirmed that the novel double adjuvants, LTB and CpG,
      are able to significantly improve GIT-induced immune responses. This formula
      could be a promising strategy for enhancing the immune efficacy of multi-subunit
      vaccines against Staphylococcus aureus and streptococcal infection.

PMID- 29458540
TI  - Survival of bactericidal antibiotic treatment by tolerant persister cells of
      Klebsiella pneumoniae.
AB  - PURPOSE: Persister cells, a subpopulation of tolerant cells within the bacterial
      culture, are commonly thought to be responsible for antibiotic therapy failure
      and infection recurrence. Klebsiella pneumoniae is a notorious human pathogen for
      its increasing resistance to antibiotics and wide involvement in severe
      infections. In this study, we aimed to investigate the persister subpopulation of
      K. pneumoniae. METHODOLOGY: The presence of persisters in K. pneumoniae was
      determined by treatment with high concentrations of antibiotics, used alone or in
      combination. The effect of low level of antibiotics on persister formation was
      investigated by pre-exposure of cells to antibiotics with low concentrations
      followed by higher doses. The dependence of persister levels on growth phase was
      determined by measuring the survival ability of cells along the growth stages
      upon exposure to a high concentration of antibiotic. Analysis on persister type
      was carried out by persister elimination assays.Results/Key findings. We show
      that K. pneumoniae produces high levels of tolerant persister cells to survive
      treatment by a variety of high concentrations of bactericidal antibiotics and
      persister formation is prevalent among K. pneumoniae clinical strains. Besides,
      we find that persister cells can be induced by low concentrations of antibiotics.
      Finally, we provide evidence that persister formation is growth phase-dependent
      and Type II persisters dominate the persister subpopulation during the entire
      exponential phase of K. pneumoniae. CONCLUSION: Our study describes the formation
      of tolerant persister cells that allow survival of treatment by high
      concentrations of antibiotics in K. pneumoniae.

PMID- 29458539
TI  - Immunogenicity in chickens with orally administered recombinant chicken-borne
      Lactobacillus saerimneri expressing FimA and OmpC antigen of O78 avian pathogenic
      Escherichia coli.
AB  - PURPOSE: Avian colibacillosis is responsible for economic losses to poultry
      producers worldwide. To combat this, we aimed to develop an effective oral
      vaccine for chicken against O78 avian pathogenic Escherichia coli (APEC)
      infection through a Lactobacillus delivery system. METHODOLOGY: Eight
      Lactobacillus strains isolated from the intestines of broiler chickens were
      evaluated based on their in vitro adherence ability to assess their potential as
      a delivery vector. Fimbrial subunit A (FimA) and outer-membrane protein C (OmpC)
      of APEC with and without fusion to dendritic cell-targeting peptide (DCpep) and
      microfold cell-targeting peptide (Co1) were displayed on the surface of
      Lactobacillus saerimneri M-11 and yielded vaccine groups (pPG-ompC-fimA/M-11 and
      pPG-ompC-fimA-Co1-DCpep/M-11, respectively). The colonization of the recombinant
      strains in vivo was assessed and the immunogenicity and protective efficacy of
      orally administered recombinant strains in chickens were evaluated. RESULTS: The
      colonization of the recombinant strains in vivo revealed no significant
      differences between the recombinant and wild-type strains. Chickens orally
      administered with vaccine groups showed significantly higher levels of OmpC/FimA
      specific IgG in serum and mucosal IgA in cecum lavage, nasal lavage and stool
      compared to the pPG/M-11 group. After challenge with APEC CVCC1553, better
      protective efficacy was observed in chickens orally immunized with pPG-ompC
      fimA/M-11 and pPG-ompC-fimA-Co1-DCpep/M-11, but no significant differences were
      observed between the two groups. CONCLUSIONS: Recombinant chicken-borne L.
      saerimneri M-11 showed good immunogenicity in chickens, suggesting that it may be
      a promising vaccine candidate against APEC infections. However, the activity of
      mammalian DCpep and Co1 was not significant in chickens.

PMID- 29458541
TI  - Direct rapid antibiotic susceptibility test (dRAST) for blood culture and its
      potential usefulness in clinical practice.
AB  - PURPOSE: The direct rapid antibiotic susceptibility test (dRAST), based on
      analysing changes in bacterial micro-colonies under antibiotic conditions,
      detects antibiotic resistance within 6 h of direct smear examination results.
      This study aimed to assess the accuracy of dRAST and evaluate its potential
      usefulness for improving selection of appropriate antibiotic in real clinical
      practice settings. METHODOLOGY: We evaluated the accuracy of dRAST by comparing
      the antibiotic treatments that should have been administered based on dRAST
      results and the broth microdilution (BMD) test and its potential usefulness via
      simulation. RESULT: For 49/52 (94.2 %) patients with Gram-positive bacteraemia
      and 66/67 (98.5 %) patients with Gram-negative bacteraemia, antibiotics indicated
      by dRAST results were the same as those indicated by the BMD test. Among 34
      patients with ineffective and suboptimal treatment, 19 (55.9 %) of patients could
      have received optimal treatment 1 to 2 days earlier with dRAST results. Among 33
      patients given unnecessary broad-spectrum antibiotics, 1 to 2 days earlier de
      escalation could have been possible for 27 (81.8 %) patients based on dRAST
      results. CONCLUSION: The introduction of dRAST could increase the use of optimal
      antibiotics and reduce unnecessary broad-spectrum antibiotic use in the early
      period of bacteraemia.

PMID- 29458542
TI  - Description of Bacillus kexueae sp. nov. and Bacillus manusensis sp. nov.,
      isolated from hydrothermal sediments.
AB  - Two Gram-staining-positive, strictly aerobic bacilli, designated as strains Ma50
      5T and Ma50-6T, were isolated from the hydrothermal sediments of Manus Basin in
      the western Pacific Ocean. Based on 16S rRNA gene sequence, strains Ma50-5T and
      Ma50-6T were most closely related to Bacillus alveayuensis (97.0 and 97.2 %
      identity, respectively). The 16S rRNA gene sequence identity between strains Ma50
      5T and Ma50-6T was 97.4 %. The identities between strains Ma50-5T and Ma50-6T and
      other closely related organisms were below 97.0 %. The G+C contents of the
      genomic DNA of strains Ma50-5T and Ma50-6T were 43.4 and 47.6 mol%, respectively.
      The major fatty acids (>10 %) of both strains were iso-C15 : 0 and iso-C17 : 0.
      The predominant isoprenoid quinone detected in both strains was menaquinone-7.
      Phylogenetic, physiological, biochemical and morphological analyses suggested
      that strains Ma50-5T and Ma50-6T represent two novel species of the genus
      Bacillus, for which the names Bacillus kexueae sp. nov. (type strain Ma50-5T=KCTC
      33881T=CCTCC AB 2017020T) and Bacillus manusensis sp. nov. (type strain Ma50
      6T=KCTC 33882T=CCTCC AB 2017019T), respectively, are proposed.

PMID- 29458543
TI  - Hymenobacter profundi sp. nov., isolated from deep-sea water.
AB  - A Gram-stain-negative, rod-shaped, red-pigmented, aerobic bacterium, strain M2T,
      was isolated from a seawater sample collected from the western Pacific Ocean at a
      depth of 1000 m and characterized using polyphasic taxonomy. Strain M2T was
      catalase-positive and oxidase-negative. Cells grew at 4-33  degrees C (optimum,
      25  degrees C), at pH 6-9 (optimum, 7) and with 0-4 % (w/v) (optimum, 1 %) NaCl.
      Phylogenetic trees based on 16S rRNA gene sequences showed that strain M2T was
      associated with the genus Hymenobacter. Strain M2T showed the highest 16S rRNA
      gene sequence similarities to Hymenobacter actinosclerus CCUG 39621T (95.7 %),
      Hymenobacter tibetensis XTM003T (95.6 %) and Hymenobacter psychrotolerans Tibet
      IIU11T (95.2 %). The DNA G+C content was 59.98 mol%. Strain M2T contained C16 :
      1omega5c (25.0 %), iso-C15 : 0 (23.9 %) and summed feature 3 (C16 : 1omega6c
      and/or C16 : 1omega7c, 20.4 %) as major cellular fatty acids. The major quinone
      of strain M2T was menaquinone 7 and the major polar lipid was
      phosphatidylethanolamine. The major polyamine of strain M2T was sym
      homospermidine. The phylogenetic analysis and physiological and biochemical data
      showed that strain M2T should be classified as representing a novel species of
      the genus Hymenobacter, for which the name Hymenobacter profundi sp. nov. is
      proposed. The type strain is M2T (=CCTCC AB 2017185T=KCTC 62120T).

PMID- 29458544
TI  - Antimicrobial activity against Mycobacterium tuberculosis under in vitro lipid
      rich dormancy conditions.
AB  - Although tuberculosis treatment is dependent on drug-susceptibility testing (DST)
      and molecular drug-resistance detection, treatment failure and relapse remain a
      challenge. This could be partially due to the emergence of antibiotic-tolerant
      dormant mycobacteria, where host lipids have been shown to play an important
      role. This study evaluated the susceptibility of Mycobacterium tuberculosis to
      two antibiotic combinations - rifampicin, moxifloxacin, amikacin and
      metronidazole (RIF-MXF-AMK-MTZ), and rifampicin, moxifloxacin, amikacin and
      pretomanid (RIF-MXF-AMK-PA) - in a lipid-rich dormancy model. Although their
      effectiveness in in vitro cultures with dextrose as a carbon source has been
      proved, we observed that none of the antibiotic mixtures were bactericidal in the
      presence of lipids. The presence of lipids may confer tolerance to M.
      tuberculosis against the mixture of antibiotics tested and such tolerance could
      be even higher during the dormant stages. The implementation of lipids in DST on
      clinical isolates could potentially lead to a better treatment strategy.

PMID- 29458545
TI  - Predominance of community-associated sequence type 59 methicillin-resistant
      Staphylococcus aureus in a paediatric intensive care unit.
AB  - PURPOSE: To investigate the distribution of molecular types of methicillin
      resistant Staphylococcus aureus (MRSA) in a paediatric intensive care unit (PICU)
      according to their community-associated (CA) and hospital-associated (HA) source
      of acquisition, and thus assess the degree to which CA-MRSA has been introduced
      into the PICU. METHODOLOGY: We implemented an MRSA surveillance in a PICU during
      2013-2016 and investigated the genetic diversity of the isolates retrospectively
      using three genetic typing methods, as well as antibiograms and virulence factor
      profiles.Results/Key findings. From 2684 specimens, we identified 60 MRSA
      isolates, 43 of which were ST59 CA-MRSA. These 43 ST59 MRSA isolates could be
      further subtyped into 2 clusters and 7 sporadic isolates by pulsed-field gel
      electrophoresis, and 3 spa types, which demonstrated the genetic diversity in
      ST59 MRSA. Phenotypic diversity was also demonstrated among these ST59 MRSA
      isolates, with 12 virulence factor profiles and 4 antibiograms being identified.
      Epidemiological information showed that 43 ST59 MRSA isolates were both community
      associated (15 isolates) and hospital-associated (28 isolates) and caused
      colonization and various types of infections in different age groups of children.
      CONCLUSIONS: Our results show that a predominant ST59 CA-MRSA has been introduced
      into the PICU to a significant extent. This has caused the ST59 HA-MRSA and CA
      MRSA in the PICU to be indistinguishable. Our results also demonstrate that when
      we are interpreting situations where the causative agents of infections focus on
      very limited pathogenic clones, combined typing methods and epidemiological
      information are needed to investigate isolates' genetic and phenotypic diversity
      to distinguish an outbreak from endemic cases.

PMID- 29458546
TI  - Pedobacter agrisoli sp. nov., isolated from farmland soil.
AB  - A Gram-stain-negative, aerobic, non-motile, non-spore-forming and rod-shaped
      bacterium, designated YHM-9T, was isolated from soil in Yangquan, Shanxi
      Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences showed
      that strain YHM-9T belonged to the genus Pedobacter and shared the highest
      similarity (97.4 %) to the type strain Pedobacter lignilitoris W-WS13T. Strain
      YHM-9T exhibited low DNA-DNA relatedness with P. lignilitoris W-WS13T (21.7+/-1.3
      %). The DNA G+C content was 38.9 mol%. The major fatty acids were iso-C15 : 0,
      summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and iso-C17 : 0 3-OH. The
      respiratory quinone was MK-7, the major polyamine was sym-homospermidine and the
      major polar lipids were phosphatidylethanolamine. Based on the morphological,
      physiological, biochemical and chemotaxonomic characteristics, strain YHM-9T was
      recognized as a representative of a novel species within the genus Pedobacter,
      for which the name Pedobacteragrisoli sp. nov. is proposed. The type strain is
      YHM-9T (=JCM 32093T=CCTCC AB 2017125T).

PMID- 29458548
TI  - Amoxicillin-tolerant Pasteurella multocida strain isolated from chronic
      dermohypodermitis after suboptimal exposure to amoxicillin is not associated with
      reduced growth rate.
AB  - Pasteurella multocida is rarely observed in human chronic infections. A
      Pasteurella multocida strain was isolated from a skin biopsy of chronic
      dermohypodermitis in a 21-year-old woman without an immunocompromised state. As
      this strain was viable one month after a cat scratch despite treatment by
      amoxicillin-clavulanic acid, we compared this strain's growth rate, amoxicillin
      Minimal Inhibitory and Bactericidal Concentrations (MIC and MBC), resistance to
      serum and ability to activate neutrophil granulocytes with those of control
      strains isolated during acute infections in humans without previous antibiotics
      exposure. This particular strain was not more resistant to serum and did not
      induce a lower phagocytic activity than control strains. It did not grow more
      slowly than control strains even after suboptimal exposure to amoxicillin. This
      particular strain was tolerant to amoxicillin but tolerance did not appear
      sufficient alone for the induction of a chronic infection in a host without an
      immunocompromised state.

PMID- 29458547
TI  - The effect of P38 MAP kinase inhibition in a mouse model of influenza.
AB  - PURPOSE: Influenza viruses are a common cause of human respiratory infections,
      resulting in epidemics of high morbidity and mortality. We investigated the
      effect of a novel mitogen-activated protein kinase (MAPK) inhibitor in vitro and
      in a murine influenza model to further explore whether p38 MAPK inhibition could
      reduce viral replication. METHODS: In vitro, the antiviral effect of p38 MAPK
      inhibitor BCT194 was evaluated in differentiated human bronchial epithelial cells
      (HBECs); in vivo, female BALB/c mice were infected intranasally with 150 pfu of
      influenza H1N1 A/Puerto Rico/8/34 and treated with BCT197 (a closely related p38
      MAPK inhibitor with an IC50 value of<1 uM, currently in clinical testing),
      dexamethasone or oseltamivir (Tamiflu) starting 24 h post infection. Body weight,
      bronchoalveolar lavage cells, cytokines, total protein and lactate dehydrogenase
      as well as serum cytokines were measured; a subset of animals was evaluated
      histopathologically.Results/Key findings. p38MAP kinase inhibition with BCT194
      had no impact on influenza replication in HBECs. When examining BCT197 in vivo,
      and comparing to vehicle-treated animals, reduced weight loss, improvement in
      survival and lack of impaired viral control was observed at BCT197 concentrations
      relevant to those being used in clinical trials of acute exacerbations of chronic
      obstructive pulmonary disease; at higher concentrations of BCT197 these effects
      were reduced. CONCLUSIONS: Compared to vehicle treatment, BCT197 (administered at
      a clinically relevant concentration) improved outcomes in a mouse model of
      influenza. This is encouraging given that the use of innate inflammatory pathway
      inhibitors may raise concerns of negative effects on infection regulation.

PMID- 29458549
TI  - Tessaracoccus aquimaris sp. nov., isolated from the intestine of a Korean
      rockfish, Sebastes schlegelii, from a marine aquaculture pond.
AB  - A novel coccus-shaped, Gram-stain-positive, non-motile and aerobic bacterium,
      designated strain NSG39T, was isolated from the intestine of a Korean rockfish,
      Sebastes schlegelii. Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that the newly isolated strain NSG39T was closely related to
      Tessaracoccus flavus RP1T (98.0 %). The isolate grew at 15-37  degrees C, pH 7-9
      and 0-4 % (w/v) salinity, with optimal growth at 30  degrees C, pH 8 and 0 %
      (w/v) salinity. The cell wall of the organism contained ll-diaminopimelic acid as
      a diagnostic diamino acid, and ribose, mannose, glucose and galactose as
      diagnostic sugars. The polar lipid comprised diphosphatidylglycerol,
      phosphatidylglycerol, three glycolipids and four unidentified polar lipids. The
      major cellular fatty acid was anteiso-C15 : 0 (47.2 %). The major menaquinone was
      MK-9 (H4). The DNA G+C content of the isolate was 68.8 mol%. The genome-based
      orthologous average nucleotide identity value for strain NSG39T and T. flavus
      RP1T was 76.6 %. Based on the phylogenetic analysis and its biological
      characteristics, strain NSG39T is considered to represent a novel species of the
      genus Tessaracoccus, for which the name Tessaracoccus aquimaris is proposed. The
      type strain is NSG39T (=KACC 17540T=JCM 19289T).

PMID- 29458550
TI  - Molecular epidemiology of Bordetella pertussis in Greece, 2010-2015.
AB  - PURPOSE: To determine the predominant strains of Bordetella pertussis in Greece
      during 2010-2015. METHODOLOGY: Infants and children (n=1150) (15 days to 14
      years) of Greek, Roma and immigrant origin with different vaccination statuses
      were hospitalized in Athens, Greece with suspected pertussis infection.
      IS481/IS1001 real-time PCR confirmed Bordetella spp./B. pertussis infection in
      300 samples. A subset of samples (n=153) were analysed by multi-locus variable
      number tandem repeat analysis (MLVA) and (n=25) by sequence-based typing of the
      toxin promotor region (ptxP) on DNA extracted from clinical specimens.Results/Key
      findings. A complete MLVA profile was determined in 66 out of 153 samples; the B.
      pertussis MLVA type 27 (n=55) was the dominant genotype and all tested samples
      (n=25) expressed the ptxP3 genotype. The vaccine coverage in the Greek population
      was 90 %; however, the study population expressed complete coverage in 2 out of
      264 infants (0-11 months) and in 20 out of 36 children (1-14 years). Roma and
      immigrant minorities represent 7 % of the Greek population, but make up 50 % of
      the study population, indicating a low vaccine coverage among these groups.
      CONCLUSIONS: The B. pertussis MT27 and ptxP3 genotype is dominant in Greek, Roma
      and immigrant infants and children hospitalized in Greece. Thus, the predominant
      MLVA genotype in Greece is similar to other countries using acellular vaccines.

PMID- 29458551
TI  - Short- and long-term influence of the levonorgestrel-releasing intrauterine
      system (Mirena(r)) on vaginal microbiota and Candida.
AB  - BACKGROUND: Recurrent vulvovaginal infections are a frequent complaint in young
      women in need of contraception. However, the influence of the contraceptive
      method on the course of the disease is not well known. AIM: To investigate the
      influence of the levonorgestrel-releasing intrauterine-system (LNG-IUS) on the
      vaginal microflora. METHODS: Short-term (3 months) and long-term (1 to 5 years)
      changes of vaginal microbiota were compared with pre-insertion values in 252
      women presenting for LNG-IUS insertion. Detailed microscopy on vaginal fluid was
      used to define lactobacillary grades (LBGs), bacterial vaginosis (BV), aerobic
      vaginitis (AV) and the presence of Candida. Cultures for enteric aerobic bacteria
      and Candida were used to back up the microscopy findings. Fisher's test was used
      to compare vaginal microbiome changes pre- and post-insertion. RESULTS: Compared
      to the pre-insertion period, we found a temporary worsening in LBGs and increased
      rates of BV and AV after 3 months of LNG-IUS. After 1 and 5 years, however, these
      changes were reversed, with a complete restoration to pre-insertion levels.
      Candida increased significantly after long-term carriage of LNG-IUS compared to
      the period before insertion [OR 2.0 (CL951.1-3.5), P=0.017]. CONCLUSIONS: Short
      term use of LNG-IUS temporarily decreases lactobacillary dominance, and increases
      LBG, AV and BV, but after 1 to 5 years these characteristics return to pre
      insertion levels, reducing the risk of complications to baseline levels. Candida
      colonization, on the other hand, is twice as high after 1 to 5 years of LNG-IUS
      use, making it less indicated for long-term use in patients with or at risk for
      recurrent vulvovaginal candidosis.

PMID- 29458552
TI  - Etest to detect drug-resistant Neisseria gonorrhoeae to contemporary treatment;
      methodological issues concerning accuracy and reproducibility.

PMID- 29458553
TI  - Streptomyces coelicolor strains lacking polyprenol phosphate mannose synthase and
      protein O-mannosyl transferase are hyper-susceptible to multiple antibiotics.
AB  - Polyprenol phosphate mannose (PPM) is a lipid-linked sugar donor used by extra
      cytoplasmic glycosyl tranferases in bacteria. PPM is synthesiszed by polyprenol
      phosphate mannose synthase, Ppm1, and in most Actinobacteria is used as the sugar
      donor for protein O-mannosyl transferase, Pmt, in protein glycosylation. Ppm1 and
      Pmt have homologues in yeasts and humans, where they are required for protein O
      mannosylation. Actinobacteria also use PPM for lipoglycan biosynthesis. Here we
      show that ppm1 mutants of Streptomyces coelicolor have increased susceptibility
      to a number of antibiotics that target cell wall biosynthesis. The pmt mutants
      also have mildly increased antibiotic susceptibilities, in particular to beta
      lactams and vancomycin. Despite normal induction of the vancomycin gene cluster,
      vanSRJKHAX, the pmt and ppm1 mutants remained highly vancomycin sensitive
      indicating that the mechanism of resistance is blocked post-transcriptionally.
      Differential RNA expression analysis indicated that catabolic pathways were
      downregulated and anabolic ones upregulated in the ppm1 mutant compared to the
      parent or complemented strains. Of note was the increase in expression of fatty
      acid biosynthetic genes in the ppm1- mutant. A change in lipid composition was
      confirmed using Raman spectroscopy, which showed that the ppm1- mutant had a
      greater relative proportion of unsaturated fatty acids compared to the parent or
      the complemented mutant. Taken together, these data suggest that an inability to
      synthesize PPM (ppm1) and loss of the glycoproteome (pmt- mutant) can
      detrimentally affect membrane or cell envelope functions leading to loss of
      intrinsic and, in the case of vancomycin, acquired antibiotic resistance.

PMID- 29458554
TI  - Genetic shifts in methicillin-resistant Staphylococcus aureus epidemic clones and
      toxin gene profiles in Japan: comparative analysis among pre-epidemic, epidemic
      and post-epidemic phases.
AB  - PURPOSE: The decline in methicillin-resistant Staphylococcus aureus (MRSA)
      isolation rates has become a general observation worldwide, including Japan. We
      hypothesized that some genetic shift in MRSA might cause this phenomenon, and
      therefore we investigated the genetic profiles among MRSA clinical isolates
      obtained from three different epidemic phases in Japan. METHODOLOGY: A total of
      353 MRSA isolates were selected from 202 medical facilities in 1990 (pre-epidemic
      phase), 2004 (epidemic phase) and 2016 (post-epidemic phase). Molecular typing
      was performed by PCR detection of 22 genes using the polymerase chain reaction
      (PCR)-based ORF typing (POT) system, including an additional eight genes
      including small genomic islets and seven toxin genes. RESULTS: Isolates with a
      POT1 of score 93, identified as presumed clonal complex (pCC)5-staphylococcal
      cassette chromosome mec (SCCmec) type II including ST5-SCCmec type II New
      York/Japan clone, represented the major epidemic MRSA lineage in 1990 and 2004.
      In 2016, however, a marked decrease in isolates with a POT1 score of 93, along
      with changes in the epidemiology of toxin genes carried, was noted, where the
      carriers of tst genes including the tst-sec combination were markedly reduced,
      and those possessing the seb gene alone were markedly increased. Rather, isolates
      with a POT1 score of 106, including pCC1 or pCC8 among the isolates with SCCmec
      type IV, which often links to community-associated MRSA, were predominant.
      Interestingly, the pCC1 and pCC8 lineages were related to sea and tst-sec
      carriage, respectively. CONCLUSIONS: Over time, a transition in MRSA genetic
      profiles from a POT1 score of 93 in 1990 and 2004 to 106 in 2014 was found in
      Japan.

PMID- 29458555
TI  - Does Toxoplasma gondii infection impact liver transplantation outcomes? A
      systematic review.
AB  - PURPOSE: Approximately one-third of the world's population has Toxoplasma gondii
      infection, and one of the main routes of transmission is organ transplantation.
      The aim of this study was to evaluate the impact of Toxoplasma infection on liver
      transplantation patients. METHODOLOGY: We searched PubMed, Lilacs, Medline,
      Science direct, Scielo, Ebsco, Springer, Wiley, Ovid and Google Scholar for
      reports published up to June 2017, and a systematic review was performed.
      RESULTS: Twenty cases were analysed before and after liver transplantation.
      Primary and reactivated infections were investigated. Before transplantation,
      positive IgG antibodies were the predominant serological markers in donors and
      recipients: 40 % (D+/R-), 20 % (D+/R+) and 20 % (D-/R+). IgM was present in only
      5 % of the donors (D+/R-). In four cases, the serological markers were not
      specified or were negative (D?/R? or D?/R-). After transplantation, IgM anti
      Toxoplasma antibodies were found in 30 % of the recipients, and in 67 % of the
      seronegative recipients the presence of Toxoplasma DNA or tachyzoites was
      reported, suggesting a primary infection. Clinical symptoms were meningitis,
      massive cerebral oedema, encephalitis and seizures. Treatment was administered in
      70 % of the patients, and 40 % died after presenting symptoms associated with
      Toxoplasma infection. CONCLUSIONS: Although we review Toxoplasma infection and
      liver transplantation cases, problems associated with the parasite may be greater
      than identified. Hence, follow-up studies on Toxoplasma infection in liver
      transplantation patients are recommended.

PMID- 29458556
TI  - Sequence analysis of the G gene of hRSVA ON1 genotype from Egyptian children with
      acute respiratory tract infections.
AB  - Human respiratory syncytial virus causes severe lower respiratory tract infection
      in neonates and children. Genotype ON1, with duplication of 72-nt in the G gene,
      was first detected in Canada and then recorded in other countries. In the current
      study, we describe the first detection of the ON1 genotype among children in
      Egypt in 2014/2015. Sequence analysis of the full-attachment G gene revealed that
      the majority of the strains examined were related to the ON1 genotype and only
      one sample related to N1 genotype. The Egyptian ON1 strains showed unique non
      silent mutations in addition to variable mutations near the antigenic sites in
      comparison to the original ON1 ancestor strain. Continuous surveillance of hRSV
      regionally and globally is needed to understand the evolutionary mechanisms and
      strategies adopted by hRSV and their inducers for better adaption to the host.

PMID- 29458557
TI  - Evaluation of greater wax moth larvae, Galleria mellonella, as a novel in vivo
      model for non-tuberculosis Mycobacteria infections and antibiotic treatments.
AB  - PURPOSE: To evaluate the suitability of Galleria mellonella larvae as an in vivo
      model and drug-screening tool for mycobacteria infections. METHODOLOGY: Larvae
      were infected using a range of inoculum sizes from a variety of rapid-growing
      mycobacteria, including strains of M. fortuitum, M. marinum and M. aurum. Larval
      survival, internal bacterial burden and the effects of amikacin, ciprofloxacin,
      ethambutol, isoniazid and rifampicin treatment on larval survival were measured
      over 144 h. The effects of these anti-mycobacterial drugs on phagocytosis and
      circulating haemocyte numbers were also examined using microscopy. RESULTS:
      Larval survival decreased after infection with M. fortuitum and M. marinum in a
      dose-dependent manner, but remained unaffected by M. aurum. Heat-killed bacteria
      did not cause larval death. Where antibiotic monotherapy was efficacious, larval
      survival post-infection increased in a dose-dependent fashion. However, efficacy
      varied between different antibiotics and species of infecting mycobacteria and,
      apart from rifampicin, efficacy in vivo correlated poorly with the in vitro
      minimum inhibitory concentrations (MICs). Combinations of antibiotics led to
      higher survival of infected larvae than antibiotic monotherapy. Selected
      antibiotic treatments that enhanced larval survival reduced the overall internal
      burden of infecting mycobacteria, but did not eradicate the pathogens.
      Administration of amikacin or ethambutol to uninfected larvae induced an initial
      transient increase in the numbers of circulating haemocytes and reduced the
      phagocytic rate of haemocytes in larvae infected with M. marinum. CONCLUSIONS:
      This report demonstrates the potential of employing a wax moth larvae model for
      studying fast-growing mycobacteria infections, and as a cheap, effective system
      for initial screening of novel treatments.

PMID- 29458558
TI  - High prevalence of fluoroquinolone resistance amongst commensal flora of
      antibiotic naive neonates: a study from India.
AB  - BACKGROUND: The emergence of resistance amongst commensal flora is a serious
      threat to the community. However, there is paucity of data regarding antibiotic
      resistance in commensals in the absence of antibiotic pressure. METHODS:
      Altogether, 100 vaginally delivered antibiotic naive exclusively breastfed
      neonates were selected. Stool samples collected on day (D)1, D21 and D60 of birth
      were cultured. Enterobacteriaceae isolates were screened for nalidixic acid (NA)
      and ciprofloxacin susceptibility as per CLSI guidelines. In 28 randomly selected
      neonates, isolates (n=92) resistant to NA and ciprofloxacin were characterized
      for the presence of plasmid-mediated quinolone resistance (PMQR) genes (qnrA,
      qnrB and qnrS, qepAand aac(6')-Ib-cr) and mutations in the quinolone resistance
      determining region (QRDR) of gyrA and parC genes by specific primers and
      confirmed by sequencing. RESULTS: A total of 343 Enterobacteriaceae were isolated
      from 100 neonates. On D1, 58 % of neonates were colonized with at least one
      Enterobacteriaceae predominantly E. coli. Overall resistance to NA was 60 % but
      ciprofloxacin resistance increased significantly from 15 % (14/96) on D1 to 38 %
      (50/132) on D60 (P-value <0.001). The predominant mechanism of fluoroquinolone
      resistance was mutation in gyrA (n=49) with or without PMQR. PMQR carrying
      isolates increased more than fivefold from D1 to D60. CONCLUSION: A high level of
      fluoroquinolone resistance in gut flora of antibiotic naive and exclusively
      breastfed neonates suggests a rampant rise of resistance in the community. The
      source of resistance genes on D1 is probably maternal flora acquired at birth.
      High load of PMQR genes in commensal flora are a potential source of spread to
      pathogenic organisms.

PMID- 29458560
TI  - cAMP-CRP acts as a key regulator for the viable but non-culturable state in
      Escherichia coli.
AB  - A variety of bacteria, including Escherichia coli, are known to enter the viable
      but non-culturable (VBNC) state under various stress conditions. During this
      state, cells lose colony-forming activities on conventional agar plates while
      retaining signs of viability. Diverse environmental stresses including starvation
      induce the VBNC state. However, little is known about the genetic mechanism
      inducing this state. Here, we aimed to reveal the genetic determinants of the
      VBNC state of E. coli. We hypothesized that the VBNC state is a process wherein
      specific gene products important for colony formation are depleted during the
      extended period of stress conditions. If so, higher expression of these genes
      would maintain colony-forming activities, thereby restraining cells from entering
      the VBNC state. From an E. coli plasmid-encoded ORF library, we identified genes
      that were responsible for maintaining high colony-forming activities after
      exposure to starvation condition. Among these, cpdA encoding cAMP
      phosphodiesterase exhibited higher performance in the maintenance of colony
      forming activities. As cpdA overexpression decreases intracellular cAMP, cAMP or
      its complex with cAMP-receptor protein (CRP) may negatively regulate colony
      forming activities under stress conditions. We confirmed this using deletion
      mutants lacking adenylate cyclase or CRP. These mutants fully maintained colony
      forming activities even after a long period of starvation, while wild-type cells
      lost most of this activity. Thus, we concluded that the lack of cAMP-CRP
      effectively retains high colony-forming activities, indicating that cAMP-CRP acts
      as a positive regulator necessary for the induction of the VBNC state in E. coli.

PMID- 29458559
TI  - Detection of novel gammaherpesviruses from fruit bats in Indonesia.
AB  - Bats are an important natural reservoir of zoonotic viral pathogens. We
      previously isolated an alphaherpesvirus in fruit bats in Indonesia, and here
      establish the presence of viruses belonging to other taxa of the family
      Herpesviridae. We screened the same fruit bat population with pan-herpesvirus PCR
      and discovered 68 sequences of novel gammaherpesvirus, designated 'megabat
      gammaherpesvirus' (MgGHV). A phylogenetic analysis of approximately 3.4 kbp of
      continuous MgGHV sequences encompassing the glycoprotein B gene and DNA
      polymerase gene revealed that the MgGHV sequences are distinct from those of
      other reported gammaherpesviruses. Further analysis suggested the existence of co
      infections of herpesviruses in Indonesian fruit bats. Our findings extend our
      understanding of the infectious cycles of herpesviruses in bats in Indonesia and
      the phylogenetic diversity of the gammaherpesviruses.

PMID- 29458561
TI  - ICTV Virus Taxonomy Profile: Guttaviridae.
AB  - Guttaviridae is a family of enveloped viruses infecting hyperthermophilic
      archaea. The virions are ovoid or droplet-shaped, with a diameter of 55-80 nm and
      a length of 75-130 nm. The genome is a circular dsDNA molecule of around 14-20
      kbp. The droplet-shaped morphology is unprecedented among viruses of bacteria and
      eukaryotes and represents a group of archaea-specific virion morphotypes. The
      family includes two genera, Alphaguttavirus and Betaguttavirus, each with a
      single species. This is a summary of the International Committee on Taxonomy of
      Viruses (ICTV) Report on the taxonomy of Guttaviridae, which is available at
      www.ictv.global/report/guttaviridae.

PMID- 29458562
TI  - The fission yeast Schizosaccharomyces pombe Mtf2 is required for mitochondrial
      cox1 gene expression.
AB  - Mitochondrial gene expression is essential for adenosine triphosphate synthesis
      via oxidative phosphorylation, which is the universal energy currency of cells.
      Here, we report the identification and characterization of a homologue of
      Saccharomyces cerevisiae Mtf2 (also called Nam1) in Schizosaccharomyces pombe.
      The Deltamtf2 mutant with the intron-containing mitochondrial DNA (mtDNA)
      exhibited impaired growth on a rich medium containing the non-fermentable carbon
      source glycerol, suggesting that mtf2 is involved in mitochondrial function. mtf2
      deletion in a mitochondrial intron-containing background resulted in a barely
      detectable level of the cox1 mRNA and a reduction in the level of the cob1 mRNA,
      and severely impaired cox1 translation. In contrast, mtf2 deletion in a
      mitochondrial intron-less background did not affect the levels of cox1 and cob1
      mRNAs. However, Cox1 synthesis could not be restored to the control level in the
      Deltamtf2 mutant with intron-less mtDNA. Our results suggest that unlike its
      counterpart in S. cerevisiae which plays a general role in synthesis of mtDNA
      encoded proteins, S. pombe Mtf2 primarily functions in cox1 translation and the
      effect of mtf2 deletion on splicing of introns in mtDNA is likely due to a
      deficiency in the synthesis of intron-encoded maturases.

PMID- 29458563
TI  - Bacillus fermenti sp. nov., an indigo-reducing obligate alkaliphile isolated from
      indigo fermentation liquor for dyeing.
AB  - The indigo-reducing, facultatively anaerobic and obligately alkaliphilic strains
      Bf-1T, Bf-2 and Bf-4 were isolated from an indigo fermentation liquor used for
      dyeing, which uses sukumo [composted Polygonum indigo (Polygonum tinctorium
      Lour.) leaves] as a basic ingredient and was obtained from a craft centre in Date
      City, Hokkaido, Japan. The 16S rRNA gene sequence analyses indicated that the
      closest neighbours of strain Bf-1T are Bacillus maritimus DSM 100413T (98.3 % 16S
      rRNA gene sequence similarity), Bacillus persicus DSM 25386T (98.2 %) and
      Bacillus rigiliprofundi LMG 28275T (97.7 %). The 16S rRNA gene sequence of strain
      Bf-1T was almost identical to the sequences of strains Bf-2 and Bf-4 (99.9 %).
      Cells of strain Bf-1T stained Gram-positive and formed straight rods that
      achieved motility through a pair of subpolar flagella. Strain Bf-1T grew at
      temperatures of between 15 and 45  degrees C with optimum growth at 33-40 
      degrees C. The strain grew in the pH range of pH 8-12, with optimum growth at pH
      10. The isoprenoid quinone detected was menaquinone-7 (MK-7), and the DNA G+C
      content was 41.7 %. The whole-cell fatty acid profile mainly (>10 %) consisted of
      iso-C15 : 0 and iso-C16 : 0. Phylogenetically related neighbours, although
      demonstrating high 16S rRNA gene sequence similarity (>97.6 %) with strain Bf-1T,
      exhibited less than 9 % relatedness in DNA-DNA hybridization experiments. Based
      on evidence from this polyphasic study, the isolates represent a novel species,
      for which the name Bacillus fermenti sp. nov. is proposed. The type strain of
      this species is Bf-1T (=JCM 31807T=NCIMB 15079T).

PMID- 29458564
TI  - Veillonella infantium sp. nov., an anaerobic, Gram-stain-negative coccus isolated
      from tongue biofilm of a Thai child.
AB  - A strain of a novel anaerobic, Gram-stain-negative coccus was isolated from the
      tongue biofilm of a Thai child. This strain was shown, at the phenotypic level
      and based on 16S rRNA gene sequencing, to be a member of the genus Veillonella.
      Comparative analysis of the 16S rRNA, dnaK and rpoB gene sequences indicated that
      phylogenetically the strain comprised a distinct novel branch within the genus
      Veillonella. The novel strain showed 99.8, 95.1 and 95.9 % similarity to partial
      16S rRNA, dnaK and rpoB gene sequences, respectively, to the type strains of the
      two most closely related species, Veillonelladispar ATCC 17748T and
      Veillonellatobetsuensis ATCC BAA-2400T. The novel strain could be discriminated
      from previously reported species of the genus Veillonella based on partial dnaK
      and rpoB gene sequencing and average nucleotide identity values. The major acid
      end-product produced by this strain was acetic acid under anaerobic conditions in
      trypticase-yeast extract-haemin with 1 % (w/v) glucose or fructose medium.
      Lactate was fermented to acetic acid and propionic acid. Based on these
      observations, this strain represents a novel species, for which the name
      Veillonella infantium sp. nov. is proposed. The type strain is T11011-4T (=JCM
      31738T=TSD-88T).

PMID- 29458565
TI  - The DNases of pathogenic Lancefield streptococci.
AB  - DNases are abundant among the pathogenic streptococci, with most species
      harbouring genes for at least one. Despite their prevalence, however, the role
      for these extracellular enzymes is still relatively unclear. The DNases of the
      Lancefield group A Streptococcus, S. pyogenes are the best characterized, with a
      total of eight DNase genes identified so far. Six are known to be associated with
      integrated prophages. Two are chromosomally encoded, and one of these is cell
      wall anchored. Homologues of both prophage-associated and chromosomally encoded
      S. pyogenes DNases have been identified in other streptococcal species, as well
      as other unique DNases. A major role identified for streptococcal DNases appears
      to be in the destruction of extracellular traps produced by immune cells, such as
      neutrophils, to ensnare bacteria and kill them. These traps are composed
      primarily of DNA which can be degraded by the secreted and cell-wall-anchored
      streptococcal DNases. DNases can also reduce TLR-9 signalling to dampen the
      immune response and produce cytotoxic deoxyadenosine to limit phagocytosis. Upper
      respiratory tract infection models of S. pyogenes have identified a role for
      DNases in potentiating infection and transmission, possibly by limiting the
      immune response or through some other unknown mechanism. Streptococcal DNases may
      also be involved in interacting with other microbial communities through
      communication, bacterial killing and disruption of competitive biofilms, or
      control of their own biofilm production. The contribution of DNases to
      pathogenesis may therefore be wide ranging and extend beyond direct interference
      with the host immune response.

PMID- 29458566
TI  - Paenibacillus translucens sp. nov., isolated from tidal flat sediment.
AB  - A Gram-stain-variable, aerobic, rod-shaped, motile and spore-forming bacterial
      strain, designated CJ11T, was isolated from a tidal flat sediment sample from
      Ganghwa-do, Republic of Korea. Strain CJ11T grew optimally on R2A at 30  degrees
      C and pH 7.0. Sequencing results of the 16S rRNA gene revealed that strain CJ11T
      possesses two copies of the 16S rRNA gene varying at five nucleotide positions.
      Phylogenetic analysis based on 16S rRNA gene sequences showed that strain CJ11T
      belonged to the genus Paenibacillus within the family Paenibacillaceae and was
      most closely related to Paenibacillus lacus KCTC 33691T (99.36-99.15 %
      similarity). DNA-DNA relatedness levels of strain CJ11T was 41.7 % (reciprocal,
      57.8 %) to P. lacus KCTC 33691T. The G+C content of the genomic DNA was 51.0
      mol%. Strain CJ11Tcontained meso-diaminopimelic acid in the cell-wall
      peptidoglycan. The major isoprenoid quinone was menaquinone-7. The major cellular
      fatty acids were anteiso-C15 : 0, C16 : 0 and iso-C16 : 0. The predominant polar
      lipids were diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine, two unidentified phospholipids, an unidentified
      glycolipid and several unidentified lipids. On the basis of the polyphasic
      taxonomic study, strain CJ11T represents a novel species in the genus
      Paenibacillus, for which the name Paenibacillustranslucens sp. nov. is proposed.
      The type strain is CJ11T (=KACC 19304T=JCM 32080T).

PMID- 29458567
TI  - Graphene-Based Multifunctional Nanomaterials in Cancer Detection and
      Therapeutics.
AB  - Nanotechnology for early diagnosis and treatment of malignant tumor is a
      forefront topic in the international field of biotechnology and medicine. In
      order to improve the effect of cancer therapy, the timely and accurate detection
      of the cancer is important and necessary. Graphene and its derivatives have
      various excellent characteristics. For example, biological sensors based on
      graphene are good at amplifying detection signals, and its derivatives play an
      important role in the early diagnosis and cancer therapy. In view of this, we
      discussed the biological sensor application based on graphene and its derivatives
      in the detection and therapy of cancer.

PMID- 29458568
TI  - Nanoformulations for Targeted Drug Delivery to Prostate Cancer: An Overview.
AB  - Cancer is the second leading causes of death worldwide and it is one of the fatal
      diseases that kill millions of people every year. It is characterized by
      uncontrolled proliferation of cells and loss of apoptosis that generates an
      abnormal mass of cells or tumors. Prostate cancer (PCa) is one of the most common
      cancers in men and the risk is higher over the age of 55-65. Currently, PCa is
      the second most common cancer, which causes death in men has a high prevalence
      with relatively lower cancer mortality risk compared to lung and colon cancer.
      Management of cancer remains an ongoing challenge in oncology as it is a
      pathophysiological and heterogeneous disease. The current treatment options such
      as surgery, chemotherapy, radiation therapy available for cancer therapies are
      inadequate due to the heterogeneity characteristics of cancer and spur demand for
      improved technologies. Nanotechnology is an emerging and potential platform that
      uses nanoparticles for the disease diagnosis to targeted drug delivery system
      (DDS). One of the most important active research fields of nanotechnology is
      nanomedicine, which provides solutions to the difficulties of conventional
      chemotherapy. Nanoformulation based drug delivery enhances the properties to
      improve the pharmacokinetics profile, bioavailability and these drug carriers
      increases the therapeutic efficiency compared to the regular chemotherapeutic
      drugs. Moreover, nanoformulated drugs help to overcome the lack of selectivity
      and adverse side effects of conventional chemotherapy. This review provides an
      overview of PCa drug delivery systems. A special emphasis is given to research
      work around the world in the development of nanoformulations for targeted drug
      delivery to PCa.

PMID- 29458569
TI  - Recent Progress of Wnt Pathway Inhibitor Dickkopf-1 in Liver Cancer.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers around the
      world. Multiple etiologic factors such as virus and environment can lead to HCC.
      It is a challenge for us to successfully detect early HCC due to the lack of
      effective characterized and specific biomarkers. However, if the early diagnosis
      is successfully realized, it provides crucial chance for HCC patients to receive
      effective treatment as early as possible. Dickkopf-1 (DKK-1) is a secretary
      glycoprotein, which negatively regulates Wnt pathway through binding to surface
      receptors LRP5/6 and Kremen 1/2. The expression of DKK-1 is regulated by p53, V
      Myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN),
      beta-catenin, etc. Ectopic expression of DKK-1 can inhibit cell proliferation, or
      induce apoptosis with apoptosis enhancing factors. DKK-1 is low-expressed in many
      tumors, but overexpressed in others. Growing evidences show that DKK-1 plays
      complex and different roles in tumorigenesis, tumor progression and metastasis of
      different cancers. We herein review the recent progress in the expression and
      function of DKK-1 in hepatocellular carcinoma.

PMID- 29458570
TI  - Functional and Modified Nanocrystals Technology for Target Drug Delivery.
AB  - In the face of a large number of insoluble drugs, the development of nanocrystals
      is effective in destroying the limits of poorly soluble drug applications and
      becoming an indispensable route of drug delivery in the pharmaceutical industry.
      In addition, the proposed delivery goal is to provide more convenience and
      benefits and the number of researchers who are developing a number of advanced
      technologies try to use improved nano-drugs to improve the bioavailability of
      drug, drug dissolution velocity and solubility. Previously, more mature study has
      been done, for example, preparation of nanocrystals, the problems of safety, the
      route of administration and so on. This review systematically dwells upon several
      of the current nanocrystals technologies for target delivery by different
      modification technologies, such as magnetic nanocrystals, PEG and PEGylated
      chitosan modified nanocrystals, cationic nanocrystals and pluronic modified
      nanocrystals. Subsequently, the effects of surface charge and particle size on
      the drug targeted administration was analyzed. This review will provide a new
      insight for improving stability and controllability of the nanocrystals, and
      promote the nanocrystals technology development in targeting drug delivery.

PMID- 29458571
TI  - Significance of Nanoparticles and the Role of Amino Acids in Structuring Them-A
      Review.
AB  - Nanoparticles has occupied an eminent place in our tech-facilitated society. The
      processes involved in synthesizing nanoparticles are important not only to find
      their applications, but also to make them eco-friendly. Attempts are being made
      to replace the use of harmful surfactants/reagents by amino acids, in the due
      course of nanoparticle synthesis. Especially in synthesizing the multifunctional
      metal and metal oxide nanoparticles the use of amino acids as surfactant/as
      catalyst, helps to obtain required size and shape. Amino acids have the inherent
      property in directing and assembling the superstructures. They have the tendency
      to act as a capping agent and their presence during the synthesis processes
      alters the synthesized particles' morphology. Review has been made to study the
      role of amino acids like histidine, lysine, arginine in structuring ZnO, FeO, Au
      and Ag nanoparticles. The change in their morphology that resulted due to the
      addition of amino acids has been compared. It is important to understand the role
      of amino acids in synthesizing the nanoparticles, and so it is more important to
      understand the internal energy variation of the same. To achieve this, the
      interaction between the bio (amino acids) and non-bio (metal and metal oxide)
      nanoparticles are to be discussed both experimentally and theoretically. At times
      the theoretical characterization, especially at low dimensions, help us to
      understand inter-particle interaction and intra-particle interaction by
      determining their chemical potential and Lennard-Jones potential. This review has
      been concluded with a model to characterize the precursor solution (amino acids
      and inorganic materials) by considering the Equation of State for liquids, which
      could also be extended to determine the structure factor of nanoparticles.

PMID- 29458572
TI  - Morphology Dependent Photocatalytic Properties of ZnO Nanostructures Prepared by
      a Carbon-Sphere Template Method.
AB  - Organic contaminants are a typical byproduct of industrial wastewater, and
      nanostructured ZnO photocatalysts have been investigated as an environmentally
      benign process to remove the contaminants through a degradation process. The
      degradation efficiency under UV irradiation can be markedly enhanced when using a
      catalyst with a nanostructure. The larger specific area of a nanostructure has
      been found to significantly enhance degradation efficiency. The complex synthesis
      process, expensive material costs, and generation of environmental contaminants
      during the synthesis process currently hinder practical application of
      photocatalysts. This research provides a template for a photocatalyst that is non
      toxic, producing mesoporous ZnO hollow spheres and nanorods through an
      environmentally friendly carbon-sphere template utilizing a hydrothermal process.
      This research demonstrates that controlling the precursor concentration (zinc
      acetate) allows for the manipulation of the morphology and specific area of the
      ZnO nanostructures. A zinc acetate concentration of 0.171 mol/L produced uniform
      ZnO mesoporous hollow spheres with diameters of approximately 180 nm. Increasing
      the zinc acetate concentration resulted in an increase in the number of nanorods
      present. In contrast to nanorods, mesoporous ZnO hollow spheres have a higher
      specific area and higher concentration of pores in the 2-50 nm range, which
      result in better photocatalytic activity. This research reports the complete
      degradation of rhodium boride (RhB) within 50 min by means of mesoporous ZnO
      hollow spheres and nanorods with a degradation rate of 0.0978 min-1.

PMID- 29458573
TI  - Promoted Delivery of Salinomycin to Lung Cancer Through Epidermal Growth Factor
      Receptor Aptamers Coupled DSPE-PEG2000 Nanomicelles.
AB  - Initiation and recurrence of lung cancer, the most fatal cancer worldwide, are
      attributed to lung cancer stem cells (CSCs). Evidence suggests that cancer cells
      can be turned into CSCs in a spontaneous way, and therefore simultaneous
      elimination of lung CSCs and cancer cells is crucial to achieve effective therapy
      of lung cancer. In lung cancer, epidermal growth factor receptor (EGFR) is
      overexpressed in both CSCs and cancer cells. The present study developed
      salinomycin poly(ethylene glycol) 2000-distearoylphosphatidylethanolamine
      nanomicelles conjugated with EGFR aptamers (M-SAL-EGFR) to kill lung CSCs and
      cancer cells. The 24 nm sized M-SAL-EGFR was prepared by a lipid film based
      method. The EGFR was overexpressed in lung CSCs and cancer cells. Results
      revealed that the M-SAL-EGFR could efficiently bind to EGFR-overexpressing lung
      CSCs and cancer cells, and induced enhanced cyotoxic effect than non-targeted M
      SAL and salinomycin. Administration of M-SAL-EGFR in mice with lung cancer
      xenograft inhibited tumor growth more effectively compared with M-SAL and
      salinomycin. The EGFR aptamers were thus able to promote effective salinomycin
      delivery to lung cancer. Our results also suggest that the M-SAL-EGFR represents
      a promising approach for targeting both lung CSCs and cancer cells.

PMID- 29458574
TI  - Thermo-Sensitive PLGA-PEG-PLGA Tri-Block Copolymer Hydrogel as Three-Dimensional
      Cell Culture Matrix for Ovarian Cancer Cells.
AB  - Thermo-sensitive hydrogels which could encapsulate cells and provide a three
      dimensional (3D) microenvironment have great potential in building new cell
      culture models in vitro. In this study, a thermal responsive hydrogel based on
      PLGA-PEG-PLGA tri-block copolymers was developed as matrix for 3D ovarian cancer
      cell culturing. The gelation of PLGA-PEG-PLGA tri-block copolymer was
      concentration-dependent. SEM images showed the pores were suitable for the
      formation of 3D cell structures. Cell morphological results showed that large
      aggregates of ovarian cancer cells (HO8910) were formed after cultured for 10
      days. Therefore, hydrogel based on PLGA-PEG-PLGA tri-block copolymers hold
      potential as in vitro cell culture matrix for ovarian cancer cells.

PMID- 29458575
TI  - Facile Preparation of Modifying Layered Double Hydroxide Nanoparticles for Drug
      Delivery.
AB  - Mg-Al-NO3 hydrotalcite (p-LDH) was employed as a carrier for the controlled
      release of 5-Fluorouracil (5-FU). The p-LDH was pretreated by acid-pretreatment
      to gain a more stable material (a-LDH) in acid medium for oral administration. It
      demonstrated that the a-LDH had smaller crystal size, particle sizes and higher
      permanent charge density (sigmap) compared with that of the p-LDH by means of
      XRD, SEM, FT-IR, UV-vis DRS, TG-DSC, BET/BJH and other techniques. The FU/a-LDH
      and FU/p-LDH delivery systems were obtained using anion-exchange method. The in
      vitro 5-FU drug release studies showed that no burst release phenomenon was
      observed at the beginning of release tests. The in vitro 5-FU release behaviors
      of the delivery systems at initial pH 4.6 and 7.5 were studied which could be
      described by first-order and Bhaskas models. Combined with the XRD and FT-IR
      analyses of the solid residues of the FU/a-LDH and FU/p-LDH after the release, it
      was found that the dissolution mechanism was mainly responsible for the release
      behavior of the FU/p-LDH at initial 4.6, while the anion-exchange between
      intercalated 5-FU and phosphate anions mechanism was responsible for the FU/a-LDH
      at pH 4.6 and 7.5 as well as FU/p-LDH at pH 7.5. It is concluded that the
      hydrotalcites could be used as the basis of a tunable drug delivery carrier for 5
      FU.

PMID- 29458576
TI  - Synthesis of Metal-Organic Framework from Iron Nitrate and 2,6
      Naphthalenedicarboxylic Acid and Its Application as Drug Carrier.
AB  - Metal-organic frameworks (MOFs) are highly crystalline porous organic-inorganic
      materials that are comprised of metal salts and organic linkers. The common
      synthetic methodologies of MOFs include: solvothermal, microwave-assisted,
      electrochemical, mechanochemical, and sonochemical routes. The synthesized MOF
      particles can be characterized using several characterization techniques
      including: X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier
      transform infrared spectroscopy (FTIR), and other analytical techniques.
      Recently, MOFs have garnered increasing attention due to their potential
      applications in numerous areas including: catalysis, gas storage and separation,
      drug delivery, and others. In this research paper, a new metal-organic framework
      was synthesized successfully from iron nitrate and 2,6-naphthalenedicarboxylic
      acid (1) by means of microwave irradiation (Fe-NDC-M) and (2) solvothermally
      using a conventional electric oven (Fe-NDC-O). They were characterized using XRD,
      SEM, FTIR, energy-dispersive X-ray (EDS), thermogravimetric analysis (TGA), and
      N2 sorption experiments. The characterization results showed that the synthesized
      samples were crystals with a rod-like shape. The particle diameters ranged
      between 50-80 nm with a length of 300-450 nm. The BJH adsorption averagepore
      diameters were found to be 148.551 A and 139.265 A for Fe-NDC-M and Fe-NDC-O,
      respectively. As a result, the new Fe-NDC-MOF particles can be used as
      nanocarriers for anticancer drug delivery applications utilizing the enhanced
      permeability and retention effect.

PMID- 29458577
TI  - A Novel Delivery Method of Cyclovirobuxine D for Brain-Targeting: Chitosan Coated
      Nanoparticles Loading Cyclovirobuxine D by Intranasal Administration.
AB  - The blood-brain barrier (BBB) restricts the delivery of most drugs to the brain.
      In our previous study, the feasibility of cyclovirobuxine D delivery to the brain
      by a non-invasive nasal route was evaluated. In this study, a suitable drug
      delivery system by way of intranasal administration was developed, which could
      improve brain targeting. First, a formulation of cyclovirobuxine D (CVB-D) based
      on chitosan nanoparticles (CS-CVB-D-NPs) was prepared by the modified ionotropic
      gelation method through single-factor screening experiment. The CS-CVB-D-NPs with
      a entrapment efficiency (EE) of (62.82+/-2.59)% were found to be of a narrow
      polydispersity index (PI) (0.19+/-0.01) and (235.37+/- 12.71) nm in size, with a
      zeta potential of (33.9 +/- 1.7) mV. The NPs possessed a sustained release
      characterization with in vitro release of 88.03 +/- 2.30% at 24 h. In vivo, the
      higher AUC0-t(brain) of CS-CVB-D-NPs by intranasal administration revealed the
      development of a novel brain-targeting delivery method of CVB-D.

PMID- 29458578
TI  - Field-Effect Transistor-Integration with TiO2 Nanoparticles for Sensing of
      Cardiac Troponin I Biomarker.
AB  - The development of electrical biosensor towards device miniaturization in order
      to achieve better sensitivity with enhanced electrical signal has certain
      limitations especially complexity in fabrication process and costs. In this
      paper, an alternative technique with minor modification in the device structure
      is presented for signal amplification by implementing ambipolar conduction in the
      biosensor itself. We demonstrated the field-effect transistor (FET)-based
      biosensor coupled back-gate for attaining a higher sensitivity with the detection
      of lower target abundance. To utilize the coupled back-gate as a pre-amplifier,
      silicon-on-insulator wafer with thicknesses of top-silicon and buried oxide (BOX)
      layers of 70 nm and 145 nm, respectively were desired. Titanium dioxide (TiO2)
      nanomaterial was deposited using sol-gel method on the channel which acts as a
      transducer. Surface functionalization on TiO2 thin film allowed an effective
      immobilization of anti-cardiac troponin I antibody to interact cardiac troponin I
      (cTnI). Binding events at each step was validated by X-ray photoelectron
      spectroscopy (XPS) analysis. Further, electrical characterization (Id-Vd)
      confirms the potentiality of FET-based biosensor to detect cTnI (represents acute
      myocardial infarction disease) with the concentration ranges from 10 MUg/ml down
      to 1 fg/ml. The sensitivity of 459.2 nA (g/ml)-1 and lower detection limit of 1
      fg/ml were achieved at Vbg = -5 V and Vd = 5 V. The designed device demonstrates
      its ability to detect lower level of cTnI with pre-amplified electrical signal by
      back-gate biasing.

PMID- 29458579
TI  - Fabrication of Calixarene Based Protein Scaffold by Electrospin Coating for
      Tissue Engineering.
AB  - In this study, calixarene was synthesized by using different functional groups as
      p-tert-butyl-Calix[4]arene ester and amides. Calixarene nanofibers were produced
      by electrospin coating. Protein immobilization onto the calixarene nanofibers was
      carried out with human serum albumin (HSA). The maximum amount of binding on
      produced three different calixarene nanofibers (DE, 2-AMP and 3-AMP) was compared
      by using a fluorescence technique for protein analysis. Result showed that
      maximum binding amount was found to be as 177.85 mg cm-2 for 3-AMP surface. The
      protein binding was also characterized by using SEM, TEM, AFM and FT-IR. From
      obtained results, calixarene-albumin nanofiber was also fabricated by spin
      coating using 3-AMP which has ability max binding of protein.

PMID- 29458580
TI  - Preparation, Characterization and Antifungal Properties of Chitosan-Silver
      Nanoparticles Synergize Fungicide Against Pyricularia oryzae.
AB  - Rice (Oryza sativa L.) is one of the major staple food crops of nearly two-third
      of the world's population. However, rice blast caused by fungus Pyricularia
      oryzae is generally considered the most serious disease of cultivated rice
      worldwide due to its extensive distribution and destructiveness under favourable
      climatic conditions. In this report, the combination between chitosan (CS) and
      silver (Ag), Ag@CS, was introduced for antifungal activity against Pyricularia
      oryzae extracted from blast-infected leaves. In detail, Ag@CS nanoparticles (NPs)
      were first synthesized and further mixed with Trihexad 700 WP (Tri), Ag@CS-Tri,
      against the fungus by agar diffusion method. The prepared Ag@CS-Tri NPs were
      characterized by Fourier transform infrared (FTIR), dynamic light scattering
      (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and
      thermogravimetric analysis (TGA). In aqueous condition, Ag@CS-Tri NPs were
      successfully prepared and existed as spherical NPs with particle size of 17.26 +/
      0.89 nm, which is an ideal size for their uptake into plant cells, indicating
      that the size of their parentally Ag@CS NPs is small enough to combine Tri, and
      their diameter is large enough to effectively penetrate the cellular membrane and
      kill fungi. More importantly, the antifungal property of Ag@CS-Tri NPs was
      significantly increased with inhibition zone around 25 nm compared with only
      around 12 nm of Ag@CS at the same concentration of Ag (2 ppm) and CS (4000 ppm).
      These results demonstrated that the synergistic effect of Tri and Ag@CS NPs can
      be a potential candidate with high antifungal activity for the use of antibiotics
      in agriculture.

PMID- 29458581
TI  - Transferrin Adsorbed on PEGylated Gold Nanoparticles and Its Relevance to
      Targeting Specificity.
AB  - Polyethylene glycol (PEG) has been frequently used for surface modification of
      nanoparticles (NPs) to reduce non-specific binding of proteins on NPs. The
      investigation of protein absorption on PEGylated nanoparticles is necessary. In
      the work, the conjugation of transferrin (Tf) to PEGylated AuNPs via adsorption
      or bonding was studied. The 13 nm AuNPs were coated with various molecular weight
      (300, 2000, 5000) carboxyl and methoxy PEG thiol. The presence of Tf on PEGylated
      AuNP was characterized by dynamic light scattering (DLS) and infrared
      spectroscopy (IR). The data of IR confirmed the presence of Tf on PEGylated
      AuNPs. The diameter decrease of PEGylated AuNPs after Tf adsorption was observed
      by DLS measurement, which is attributed to competitive adsorption between Tf and
      PEG molecules. These phenomena may be important to the preservation of Tf
      targeting specificity on PEGylated AuNPs.

PMID- 29458582
TI  - Magnetic Lamellar Nano-Hydroxyapatite as a Vector for Gene Transfection in Three
      Dimensional Cell Culture.
AB  - Compared to two-dimensional (2D) conditions, investigation on gene transfection
      in three-dimensional (3D) conditions is much less extensive. In this work,
      lamellar nano-hydroxyapatite (L-HAp) with and without magnetism were used as the
      vectors and gene transfection in 2D and 3D cell culture was carried out and
      compared. We found that the transfection efficiency in 3D conditions was much
      higher than 2D cell culture. Additionally, magnetism enhanced transfection
      efficiency under both 2D and 3D conditions. The findings presented in this study
      demonstrated that the magnetic L-HAp could be a promising vector in 3D gene
      transfection.

PMID- 29458583
TI  - Nanostructured Layered Terbium Hydroxide Containing NASIDs: In Vitro
      Physicochemical and Biological Evaluations.
AB  - Diclofenac sodium (abrr. DS) and indomethacin (abrr. IMC) have been intercalated
      into the layered terbium hydroxide (LTbH) by anion exchange method. Chemical
      compositions, thermostability, morphology, luminescence property, release
      behaviors and cytotoxic effects have been investigated. The DS molecules may
      embed between layers with a bilayered arrangement and the IMC may correspond to a
      monolayered arrangement. The Tb3+ luminescence in DS-LTbH and IMC-LTbH composites
      were enhanced compared with LTbH precusor and the luminescence intensity
      increases with the deprotonation degree. Drug release was measured with HPLC, and
      LTbH showed sustained release behavior on both drugs. Further In Vitro evaluation
      were carried out on cancer cells. Cytotoxic effect of LTbH was observed with a
      sulforhodamine B colorimetric assay on a variety of cancer cell lines, which
      revealed that the LTbH showed little cytotoxic effect. Results indicate LTbH may
      offer a potential vehicle as an effective drug delivery system along with
      diagnostic integration.

PMID- 29458584
TI  - Synthesis of Carbon Dots from Pear Juice for Fluorescence Detection of Cu2+ Ion
      in Water.
AB  - In this work, a facile green hydrothermal method was developed for the synthesis
      of carbon dots with fluorescent property using pear juice as raw materials. The
      synthesized carbon dots were characterized by UV-vis, fluorescence and
      transmission electron microscopic techniques. The synthesized conditions were
      optimized and the obtained carbon dots exhibited an average size at 10 nm with
      bright emission centered at 455 nm (blue color) under UV light with the
      excitation wavelength at 360 nm. The as-prepared carbon dots exhibited quenching
      effect in the presence of Cu2+ ion and a method for Cu2+ ion detection in water
      was developed with acceptable selectivity. The synthesized fluorescent carbon
      dots showed advantages like easy preparation, low cost and environmental
      friendly. It could be useful in chemical and biochemical detection.

PMID- 29458585
TI  - "Turn-On" Fluorescent and Colorimetric Detection of Zn2+ Ions by Rhodamine
      Cinnamaldehyde Derivative.
AB  - We report the design and synthesis of a novel chemosensor (Rh6G-Cin) rhodamine
      based indicator for selective detection of Zn2+ ion. Rh6G-Cin displayed high
      selectivity towards Zn2+ from various metal ions, including Ca2+, Ag+, Cd2+,
      Co2+, Cu2+, Al3+, Zn2+, Cr3+, Ba2+, Fe2+, Fe3+, Gd3+, Hg2+, Mg2+, Mn2+, Nd3+,
      Pb2+, Sr2+ and Ni2+, and the resultant complex is [Rh6G-Cin-Zn2+]. The obvious
      change from colorless to pink upon the addition of Zn2+ could make it a suitable
      "naked eye" indicator for Zn2+. More significantly, the sensor displayed a
      remarkable colorless to yellowish green fluorescence switch in the presence of
      Zn2+ ions. The ring-opening mechanism of the rhodamine spirolactam was induced by
      Zn2+ binding, and the 3:1 stoichiometric structure between Rh6G-Cin and Zn2+ was
      adequately supported by the Job's plot evaluation, optical titration and 1H NMR
      results.

PMID- 29458586
TI  - Biosynthesis of Gold and Silver Nanoparticles Using Extracts of Callus Cultures
      of Pumpkin (Cucurbita maxima).
AB  - The potential of callus cultures and field-grown organs of pumpkin (Cucurbita
      maxima) for the biosynthesis of nanoparticles of the noble metals gold and silver
      has been investigated. Biosynthesis of AuNPs (gold nanoparticles) and AgNPs
      (silver nanoparticles) was obtained with flowers of C. maxima but not with pulp
      and seeds. With callus cultures established in MS-based medium the biogenesis of
      both AuNPs and AgNPs could be obtained. At 65  degrees C the biogenesis of AuNPs
      and AgNPs by callus extracts was enhanced. The AuNPs and AgNPs have been
      characterized by UV-visible spectroscopy, TEM, DLS and XRD. Well-dispersed
      nanoparticles, which exhibited a remarkable diversity in size and shape, could be
      visualized by TEM. Gold nanoparticles were found to be of various shapes, viz.,
      rods, triangles, star-shaped particles, spheres, hexagons, bipyramids, discoid
      particles, nanotrapezoids, prisms, cuboids. Silver nanoparticles were also of
      diverse shapes, viz., discoid, spherical, elliptical, triangle-like, belt-like,
      rod-shaped forms and cuboids. EDX analysis indicated that the AuNPs and AgNPs had
      a high degree of purity. The surface charges of the generated AuNPs and AgNPs
      were highly negative as indicated by zeta potential measurements. The AuNPs and
      AgNPs exhibited remarkable stability in solution for more than four months. FTIR
      studies indicated that biomolecules in the callus extracts were associated with
      the biosynthesis and stabilisation of the nanoparticles. The synthesized AgNPs
      could catalyse degradation of methylene blue and exhibited anti-bacterial
      activity against E. coli DH5alpha. There is no earlier report of the biosynthesis
      of nanoparticles by this plant species. Callus cultures of Cucurbita maxima are
      effective alternative resources of biomass for synthesis of nanoparticles.

PMID- 29458587
TI  - Investigation on the Magnetically Separable Zn Substituted CoFe2O4 Nanoparticles
      with Enhanced Photo-Fenton Degradation.
AB  - We report the influence of Co1-xZnxFe2O4 nanoferrites for the photodegradation of
      organic pollutant present in the aqueous solution. A series of Co1-xZnxFe2O4 (x =
      0.01, 0.03, 0.05 and 0.10) nanoferrites have been synthesized via a facile and
      economically viable coprecipitation technique and investigated the effect of zinc
      dopant in their structural, optical, electrical and magnetic properties. X-ray
      diffraction and Fourier Transform Infrared spectral studies reveal the spinel
      phase formation of the as-synthesized nanoferrites. Photoluminescence and UV
      visible spectral studies show the bandgap of nanoferrites increase from 2.47-2.67
      eV and exhibited a blue shift in the band edge emission with respect to increase
      in Zn content. Phase transition of the samples from weak ferromagnetic to
      superparamagnetic nature has been observed by Vibrating Sample Magnetometer at
      room temperature. Furthermore, the Co1-xZnxFe2O4 was assessed for the degradation
      of Methylene Blue (MB) dye and the sample with Co1-0.10Zn0.10Fe2O4 showed better
      photocatalytic degradability of organic MB due to its enhanced adsorption in the
      visible region and the existence of lower concentration charge-carriers.

PMID- 29458588
TI  - Liquid Phase Catalytic Oxidation of Toluene Over Rich Silica and Alumina
      Composition of Hierarchical Ordered ZSM-5 Zeolites Prepared Without Organic
      Templates.
AB  - Hierarchical ordered ZSM-5 zeolites were successfully synthesized by a template
      free hydrothermal treatment using rice joints ash as the source of silica. The
      formation of hierarchical ordered ZSM-5 zeolites and its physicochemical
      properties were investigated systematically. The mineralogical phases,
      morphology, surface area and porosity, acidity and thermal stability of the
      synthesized hierarchical materials were investigated using XRD, FT-IR, HR-SEM, N2
      adsorption-desorption (BET) analysis, NH3-TPD and TGA/DTA analysis. The excellent
      catalytic activity of hierarchical ordered ZSM-5 zeolites (150  degrees C) was
      revealed in the selective oxidation of toluene to the corresponding benzaldehyde
      with 82% conversion and 94% selectivity. The material was evaluated for the
      oxidation of toluene in the presence of H2O2 as the oxidizing agent and 1,4
      dioxane solvent. The obtained results noted that the material was highly active,
      stable and can be recycled at least four times without a loss of catalytic
      efficiency. The crystallization was carried out in an autoclave for 5 days
      maintained at a temperature of 150  degrees C for the transformation of RJA into
      hierarchical ZSM-5 zeolite structure as well as to achieve high crystallinity.

PMID- 29458589
TI  - Neurotransmitter Dopamine Enhanced Sensing Detection Using Fibre-Like Carbon
      Nanotubes by Chemical Vapor Deposition Technique.
AB  - Carbon nanotubes (CNTs) are still receiving much attention in bio-sensing
      applications due to their remarkable properties. In this present research work,
      fibre-like carbon nanotubes (f-CNTs) were successfully fabricated over copper
      molybdenum (Cu-Mo) substituted alumina nanoparticles at atmospheric pressure by
      chemical vapor deposition (CVD) technique and effectively employed as a
      neurotransmitter dopamine (DA) sensor. The obtained product was purified and
      structurally characterized by various techniques such as, field emission scanning
      electron microscope (FESEM), energy dispersive X-ray spectroscopy (EDX), Raman
      spectroscopy, high resolution transmission electron microscope (HRTEM) and X-ray
      photoelectron spectroscopy (XPS) analysis. Structural characterization, which
      reveals the material contains fibre-like multi walled carbon nanotubes with
      graphene layers having diameter in the range of 10-20 nm and 200-300 nm inner and
      outer, respectively and has certain crystallinity. The weight percentages of Cu,
      Mo in Alumina catalyst, reaction temperature, acetylene flow rate and reaction
      time have been optimised to yield maximum of carbon product. Electrochemical
      properties of the material towards DA sensing were studied by cyclic voltammetry
      (CV), and diffuse pulse voltammetry (DPV) techniques. The sensor exhibits linear
      relationship among the peak current and DA concentration from 8 to 45 MUM with
      detection limit of 5.3 MUM (S/N = 3). The presence of structural analogues of DA
      has no deleterious effect on the DA anodic peak current.

PMID- 29458590
TI  - Synthesis of Mesoporous Nanocrystalline Zirconia by Surfactant-Assisted
      Hydrothermal Approach.
AB  - In this paper, we have reported the chemical synthesis of thermally stable
      mesoporous nanocrystalline zirconia with high surface area using a surfactant
      assisted hydrothermal approach. We have employed different type of surfactants
      such as CTAB, SDS and Triton X-100 in our synthesis. The synthesized
      nanocrystalline zirconia multistructures exhibit various morphologies such as
      rod, mortar-pestle with different particle sizes. We have characterized the
      zirconia multistructures by X-ray diffraction study, Field emission scanning
      electron microscopy, Attenuated total refection infrared spectroscopy, UV-Vis
      spectroscopy and photoluminescence spectroscopy. The thermal stability of as
      synthesized zirconia multistructures was studied by thermo gravimetric analysis,
      which shows the high thermal stability of nanocrystalline zirconia around 900 
      degrees C temperature.

PMID- 29458591
TI  - Asymmetric Low Temperature Bonding Structure with Thin Solder Layers Using Ultra
      Thin Buffer Layer.
AB  - Asymmetric Cu to In/Sn bonding structure with Ni ultrathin buffer layer (UBL) on
      Cu side is investigated in this research. The usage of Ni UBL slows down
      intermetallic compound (IMC) formation during bonding. Asymmetric structure can
      separate electrical isolation and solder process to avoid interaction, which can
      prevent IMC formation during polymer curing. A well-bonded asymmetric structure
      can be achieved with submicron solder by 150  degrees C bonding for 15 min. The
      structure shows the potential for low temperature hybrid bonding technology in
      high-density three-dimensional (3D) integration.

PMID- 29458592
TI  - Nanocrystalline Hierarchical ZSM-5: An Efficient Catalyst for the Alkylation of
      Phenol with Cyclohexene.
AB  - In this paper, authors report the synthesis of nanocrystalline hierarchical
      zeolite ZSM-5 and its application as a heterogeneous catalyst in the alkylation
      of phenol with cyclohexene. The catalyst was synthesized by vacuum-concentration
      coupled hydrothermal technique in the presence of two templates. This synthetic
      route could successfully introduce pores of higher hierarchy in the zeolite ZSM-5
      structure. Hierarchical ZSM-5 could catalyse effectively the industrially
      important reaction of cyclohexene with phenol. We ascribe the high efficiency of
      the catalyst to its conducive structural features such as nanoscale size, high
      surface area, presence of hierarchy of pores and existence of Lewis sites along
      with Bronsted acid sites. The effect of various reaction parameters like
      duration, catalyst amount, reactant mole ratio and temperature were assessed.
      Under optimum reaction conditions, the catalyst showed up to 65% selectivity
      towards the major product, cyclohexyl phenyl ether. There was no discernible
      decline in percent conversion or selectivity even when the catalyst was re-used
      for up to four runs. Kinetic studies were done through regression analysis and a
      mechanistic route based on LHHW model was suggested.

PMID- 29458593
TI  - Corrosion Protection of Copper in 3% NaCl Solution by the Fabrication of
      Thiadiazole Monolayer.
AB  - In this study, 2-mercapto-1,3,4-thiadiazole (2-MT) self-assembled monolayer (SAM)
      was formed on copper electrode surface and the resulting 2-MT SAM on copper has
      been characterized using surface analytical techniques such as Fourier transform
      infrared (FT-IR) spectroscopy, energy dispersive X-ray (EDX) analysis, atomic
      force microscopy (AFM) and contact angle measurement (CA). The existence of N and
      S in the EDX and FT-IR analysis showed that 2-MT molecules were self-assembled on
      the copper through N and S by chemisorption which indicates the formation of 2-MT
      SAM on copper surface. Corrosion protection performance of 2-MT SAM on copper was
      investigated using potentiodynamic polarization studies (PDS), cyclic voltammetry
      (CV) and scanning electron microscopy (SEM), respectively. Analysis of both
      electrochemical and SEM analysis results revealed excellent corrosion protection
      for the copper substrate.

PMID- 29458594
TI  - Three Dimensional Nitrogen-Doped and Nitrogen, Sulfur-Codoped Graphene Hydrogels
      for Electrode Materials in Supercapacitors.
AB  - In present work, reduced graphene oxide hydrogels (RGOHs) with three-dimensional
      (3D) porous structure are prepared through chemical reduction method by using
      aminourea (NRGOHs) and aminothiourea (NSRGOHs) as reductants. The as-prepared
      RGOHs are considered not only as promising electrode materials for
      supercapacitors, but also the doping of nitrogen (aminourea, NRGOHs) or
      nitrogen/sulfur (aminothiourea, NSRGOHs) can improve electrochemical performance
      through faradaic pseudocapacitance. The optimized samples have been prepared by
      controlling the mass ratios of graphene oxide (GO) to aminourea or aminothiourea
      to be 1:1, 1:2 and 1:5, respectively. With adding different amounts of aminourea
      or aminothiourea, the obtained RGOHs exhibited different electrochemical
      performance in supercapacitors. With increasing the dosage of the reductants, the
      RGOHs revealed better specific capacitances. Moreover, NSRGOHs with nitrogen,
      sulfur-codoping exhibited better capacitance performance than that of NRGOHs with
      only nitrogen-doping. NSRGOHs showed excellent capacitive performance with a very
      high specific capacitance up to 232.2, 323.3 and 345.6 F g-1 at 0.2 A g-1, while
      NRGOHs showed capacitive performance with specific capacitance up to 220.6, 306.5
      and 332.7 F g-1 at 0.2 A g-1. This provides a strategy to improve the capacitive
      properties of RGOHs significantly by controlling different doping the materials.

PMID- 29458595
TI  - Synthesis and Luminescence Properties of a Novel Yellow-White Emitting
      NaLa(MoO4)2: Dy3+, Li+ Phosphor.
AB  - Intense yellow-white NaLa(MoO4)2: Dy3+ phosphors co-doped with Li+ ions have been
      successfully synthesized via facile sol-gel combustion approach. The dependence
      of the crystal structure and crystallinity, particle morphology,
      photoluminescence property, fluorescent lifetime and absolute quantum efficiency
      of the as-prepared phosphors has been investigated. Stable yellow-white emission
      from 440 nm to 600 nm and higher absolute quantum efficiency were studied on Dy3+
      doped NaLa(MoO4)2, Dy3+ and Li+ co-doped NaLa(MoO4)2, respectively. Surprisingly,
      only a small amount of Li+ can lead to a remarkable increase of the PL intensity
      and the quantum efficiency. Especially, along with 0.75 mol% Li+ ions induced in
      the NaLa(MoO4)2: Dy3+ phosphors, the absolute quantum efficiency increased from
      13.8% to 22%, and the possible mechanism has been deeply discussed. Outstanding
      luminescence properties have certified that NaLa(MoO4)2: Dy3+, Li+ phosphors are
      promising candidates as new yellow-white components for optical devices.

PMID- 29458596
TI  - Optical, Magnetic and Photocatalytic Activity Studies of Li, Mg and Sr Doped and
      Undoped Zinc Oxide Nanoparticles.
AB  - Nanoparticles of Li, Mg and Sr doped and undoped zinc oxide was prepared by
      simple precipitation method. The structural, optical, and magnetic properties of
      the samples were investigated by the Powder X-ray Diffraction (XRD), Scanning
      Electron Microscope (SEM), Transmission Electron Microscope (TEM), Fourier
      Transform Infrared (FTIR) spectroscopy, Ultra-violet Visible spectroscopy (UV
      vis) spectra, Photoluminescence (PL) and Vibrational Sample Magnetometer (VSM).
      The Powder X-ray diffraction data confirm the formation of hexagonal wurtzite
      structure of all doped and undoped ZnO. The SEM photograph reveals that the pores
      availability and particles size in the range of 10 nm-50 nm. FTIR and UV-Visible
      spectra results confirm the incorporation of the dopant into the ZnO lattice
      nanostructure. The UV-Visible spectra indicate that the shift of blue region
      (lower wavelength) due to bandgap widening. Photoluminescence intensity varies
      with doping due to the increase of oxygen vacancies in prepared ZnO. The pure ZnO
      exist paramagnetic while doped (Li, Mg and Sr) ZnO exist ferromagnetic property.
      The photocatalytic activity of the prepared sample also carried out in detail.

PMID- 29458597
TI  - Detonation Nanodiamonds as a New Tool for Phenol Detection in Aqueous Medium.
AB  - This paper demonstrates the effectiveness of using detonation nanodiamonds (DNDs)
      for detecting phenol in aqueous medium. The study has shown that the catalytic
      effect of DNDs in the oxidative azo coupling reaction (phenol-4-aminoantipyrine
      hydrogen peroxide) is produced by trace amounts of iron and copper ions adsorbed
      on the surface of nanoparticles. The effectiveness of DNDs as a catalyst is
      determined by the amounts of these adsorbates and can be enhanced by a factor of
      two by additional adsorption of these ions onto the nanoparticles. A rise in the
      temperature of the DND-catalyzed azo coupling reaction leads to a considerable
      (4.5-fold) increase in the reaction product yield. DNDs used to detect phenol in
      aqueous medium enable a linear increase in the yield of the product of the azo
      coupling reaction at concentrations of the analyte of between 0.05 and 10 MUg/ml.
      The study demonstrates that DNDs can be reused to detect phenol in water samples.

PMID- 29458598
TI  - A High Sensitivity Isopropanol Vapor Sensor Based on Cr2O3-SnO2 Heterojunction
      Nanocomposites via Chemical Precipitation Route.
AB  - Cr2O3-SnO2 heterojunction nanocomposites were prepared via chemical precipitation
      method. The prepared samples were characterized by X-ray diffraction (XRD),
      Transmission electron microscopy (TEM), UV-Vis diffuse reflectance spectra and
      Field Emission Electron Microscopy (FESEM). The XRD spectrum confirms the
      presence of both tetragonal rutile SnO2 and rhombohedral corundum Cr2O3
      structure. Further investigation into the gas sensing performances of the
      prepared Cr2O3-SnO2 nanocomposites exhibited an enhanced sensitivity towards VOPs
      such as isopropanol, acetone, ethanol and formaldehyde. Especially, isopropanol
      vapor sensor shows excellent sensitivity at an operating temperature of 100 
      degrees C. The highest sensitivity for Cr2O3-SnO2 heterojunction nanocomposites
      indicate that these materials can be a good candidate for the production of high
      performance isopropanol sensors.

PMID- 29458599
TI  - Multifunctional Silver-Cellulose Nanocomposite as a Promising Plasmonic Sensing
      Platform.
AB  - Cellulose paper based multifunctional nanoplatform shows great promise towards
      molecular sensing and diagnostics application due to their sustainability,
      biocompatibility, affordability, environmental appeal and broad chemical
      modification capabilities. Herein, we have effectively synthesized plasmonic
      silver-cellulose nanocomposite (SCN) using complete green and in situ approach
      using the hydroxyl groups of cellulose paper acting as the reducing agent and
      stabilizing agent. The fabricated SCN were investigated and characterized by SEM,
      UV-Vis, DLS, PXRD and EDX. The important influencing parameters such as
      temperature and pH were optimized during the fabrication of SCN. Besides, this
      SCN functionalized with 3-aminopropyltriethoxysilane and has been exploited for
      monitoring of fluoride ion from water samples with distinguishing F- from a wide
      range of environmental prevalent ions. These remarkable properties of SCN have
      been used as rapid, portable test panel which could be simple, lightweight and
      disposable.

PMID- 29458600
TI  - Facile Synthesis of Nitrogen Doped Graphene Oxide from Graphite Flakes and
      Powders: A Comparison of Their Surface Chemistry.
AB  - Nitrogen-doped graphene oxide (NGO) nanosheets were prepared via a facile one-pot
      modified Hummer's approach at low temperatures using graphite powder and flakes
      as starting materials in the presence of a nitrogen precursor. It was found that
      the morphology, structure, composition and surface chemistry of the NGO
      nanosheets depended on the nature of the graphite precursor used. GO nanosheets
      doped with nitrogen atoms exhibited a unique structure with few thin layers and
      wrinkled sheets, high porosity and structural defects. NGO sheets made from
      graphite powder (NGOp) exhibited excellent thermal stability and remarkably high
      surface area (up to 240.53 m2 .g-1) compared to NGO sheets made from graphite
      flakes (NGOf) which degraded at low temperatures and had an average surface area
      of 24.70 m2 .g-1. NGOf sheets had a size range of 850 to 2200 nm while NGOp
      sheets demonstrated obviously small sizes (460-1600 nm) even when exposed to
      different pH conditions. The NGO nanosheets exhibited negatively charged surfaces
      in a wide pH range (1 to 12) and were found to be stable above pH 6. In addition,
      graphite flakes were found to be more suitable for the production of NGO as they
      produced high N-doping levels (0.65 to 1.29 at.%) compared to graphite powders
      (0.30 to 0.35 at.%). This study further demonstrates that by adjusting the amount
      of N source in the host GO, one can tailor its thermal stability, surface
      morphology, surface chemistry and surface area.

PMID- 29458602
TI  - Fe-Dy Nanogranular Thin Films: Investigation of Structural, Microstructural and
      Magnetic Properties.
AB  - A series of Fe100-xDyx thin films with the concentration range x = 6 to 35 were
      fabricated by dc magnetron sputtering process. X-ray diffraction and TEM studies
      revealed that films have separate Fe and Dy nanograins and that there is no
      intermixing of Fe and Dy thus forming nanogranular films. This unmixed behaviour
      in our thin films is very different from the bulk Fe-Dy alloys where several
      stoichiometric compounds can be formed. Magnetic properties of the films have
      been systematically studied. The contribution to the total magnetization is due
      to the Fe grains and the Dy grains are paramagnetic down to 4 K. The saturation
      magnetization of all the samples is significantly lower than that of bulk Fe due
      to the existence of superparamagnetic Fe grains. Upon increasing x, the in-plane
      magnetic anisotropy is found to decrease and the samples become isotropic. The
      zero field cooled and field cooled magnetization measurements also confirmed the
      presence of the superparamagnetic Fe grains.

PMID- 29458601
TI  - Novel CsxWO3/TiO2 Microspheres as Enhanced Visible Light Photocatalysts for Dye
      Pollutant Treatments.
AB  - CsxWO3/TiO2 composites with different contents of CsxWO3 were successfully
      synthesized in this study by a facile hydrothermal process. CsxWO3/TiO2
      composites were characterized by XRD, Raman, UV-visible diffuse reflectance
      spectra (DRS), photoluminescence spectra (PL) and SEM. TiO2 nanoparticles were
      distributed uniformly on the surface of the CsxWO3 microsphere in the prepared
      CsxWO3/TiO2 composites, and they formed heterojunctions with CsxWO3. The effect
      of CsxWO3 on the photoactivities of composites was investigated via DRS and PL.
      All CsxWO3/TiO2 catalysts showed enhanced photocatalytic activity for degrading
      rhodamine B under visible light irradiation. The 50% CsxWO3/TiO2 sample showed
      the best photocatalytic activity and its kinetic constant was 20 times larger
      than that of TiO2. The possible photocatalytic mechanism is also discussed from
      the trapping experiments of active species. The improved photocatalytic activity
      for the CsxWO3/TiO2 catalyst may be attributed to the synergetic effect between
      CsxWO3 microspheres and TiO2 nanoparticles. This novel photocatalyst can be used
      to degrade environmental pollutants in the future.

PMID- 29458603
TI  - Mesoporous g-C3N4 Nanosheets: Synthesis, Superior Adsorption Capacity and
      Photocatalytic Activity.
AB  - Elimination of pollutants from water is one of the greatest challenges in
      resolving global environmental issues. Herein, we report a high-surface-area
      mesoporous g-C3N4 nanosheet with remarkable high adsorption capacity and
      photocatalytic performance, which is prepared through directly polycondensation
      of urea followed by a consecutive one-step thermal exfoliation strategy. This one
      pot method to prepare mesoporous g-C3N4 nanosheet is facile and rapid in
      comparison with others. The superior adsorption capacity of the fabricated
      mesoporous g-C3N4 nanostructures is demonstrated by a model organic pollutant
      methylene blue (MB), which is up to 72.2 mg/g, about 6 times as that of the
      largest value of various g-C3N4 adsorbents reported so far. Moreover, this kind
      of porous g-C3N4 nanosheet exhibits high photocatalytic activity to MB and phenol
      degradation. Particularly, the regenerated samples show excellent performance of
      pollutant removal after consecutive adsorption/degradation cycles. Therefore,
      this mesoporous g-C3N4 nanosheet may be an attractive robust metal-free material
      with great promise for organic pollutant elimination.

PMID- 29458604
TI  - Measuring the Acoustic Release of a Chemotherapeutic Agent from Folate-Targeted
      Polymeric Micelles.
AB  - In this paper, we compare the use of Bayesian filters for the estimation of
      release and re-encapsulation rates of a chemotherapeutic agent (namely
      Doxorubicin) from nanocarriers in an acoustically activated drug release system.
      The study is implemented using an advanced kinetic model that takes into account
      cavitation events causing the antineoplastic agent's release from polymeric
      micelles upon exposure to ultrasound. This model is an improvement over the
      previous representations of acoustic release that used simple zero-, first- and
      second-order release and re-encapsulation kinetics to study acoustically
      triggered drug release from polymeric micelles. The new model incorporates drug
      release and micellar reassembly events caused by cavitation allowing for the
      controlled release of chemotherapeutics specially and temporally. Different
      Bayesian estimators are tested for this purpose including Kalman filters (KF),
      Extended Kalman filters (EKF), Particle filters (PF), and multi-model KF and EKF.
      Simulated and experimental results are used to verify the performance of the
      above-mentioned estimators. The proposed methods demonstrate the utility and high
      accuracy of using estimation methods in modeling this drug delivery technique.
      The results show that, in both cases (linear and non-linear dynamics), the
      modeling errors are expensive but can be minimized using a multi-model approach.
      In addition, particle filters are more flexible filters that perform reasonably
      well compared to the other two filters. The study improved the accuracy of the
      kinetic models used to capture acoustically activated drug release from polymeric
      micelles, which may in turn help in designing hardware and software capable of
      precisely controlling the delivered amount of chemotherapeutics to cancerous
      tissue.

PMID- 29458605
TI  - Preparation of Zn-Doped Biochar from Sewage Sludge for Chromium Ion Removal.
AB  - Recycling and reuse waste can result in significant savings in materials and
      energy. In this study, the adsorption of Cr(VI) was analyzed using activated
      carbon (AC) and biochar (BSC) made from sewage sludge. BSC materials were
      synthesized using zinc chloride as an activator coupled with carbonized sewage
      sludge. Specific surface area, pore size distribution, and pore volume were
      determined by measuring nitrogen adsorption-desorption (BET). BSC morphology was
      measured using field-emission scanning electron microscopy (SEM) with energy
      dispersive X-ray spectroscopy (EDS). Results showed that the surface area and
      average pore volume of the BSC were 490 m2 g-1 and 0.8 cm3 g-1, respectively. SEM
      results revealed that BSC had uniform pore size. Effects of varying the initial
      Cr(VI) concentrations, pH values, and dosages of BSC on adsorption performance
      were also determined. Results showed that the maximum removal efficiency of
      Cr(VI) was above 99%, and adsorption capacity of 50% ZnCl2-BSC was 677 mg g-1.

PMID- 29458606
TI  - The Optimization of Gate All Around-L-Shaped Bottom Select Transistor in 3D NAND
      Flash Memory.
AB  - In this work, the GAA (Gate All Around) L-Shaped bottom select transistor (BSG)
      in 3D NAND Flash Memory has been investigated. Different methods are proposed to
      optimize its performance from viewpoints of process and structure. BSG in 3D NAND
      is a novel device structure with two connected transistors: one is horizontal
      MOSFET (regarded as convention MOSFET) and one is vertical MOSFET (regarded as
      GAA transistor). With implant dose increasing in vertical channel, BSG Vth has
      much more tighter Vt distribution, which is beneficial for boosting potential
      improvement and program disturbance suppression. Meanwhile, BSG corner rounding
      is proposed to improve the characteristic of BSG. Experiment and TCAD simulation
      data are matches quite well, giving a way to improve cell characteristics
      distribution and self-boosting potential control in high density 3D NAND array.

PMID- 29458607
TI  - Thienoisoindigo-Based Polymers Bearing Diethynylbenzene and Diethynylanthracene
      Units for Thin Film Transistors and Solar Cells.
AB  - Two thienoisoindigo-based donor-acceptor conjugated polymers were synthesized via
      Sonogashira coupling reaction with 1,4-diethynylbenzene (P(TII-BEN)) and 9,10
      diethynylanthracene (P(TII-ANT)) as donor units, respectively. The optical and
      electrochemical properties of the polymers were also investigated. The highest
      hole mobility were 4.38 * 10-3 cm2 V-1 s-1 for P(TII-BEN) and 9.40 * 10-3 cm2 V-1
      s-1 for P(TII-ANT) in bottom-gated/top-contact field-effect transistors. The bulk
      heterojunction organic solar cells consisting of the polymers and PC71BM yielded
      power conversion efficiencies of 1.59% for P(TII-BEN) and 1.90% for P(TII-ANT).
      Moreover, the microstructures were investigated by X-ray diffraction and atomic
      force microscopy.

PMID- 29458608
TI  - Thermal Unfolding Process of Lysozyme on PEGylated Gold Nanoparticles Reveals
      Length-Dependent Effects of PEG Layer.
AB  - Characterization of bio-nano interface is crucial for developing safer and more
      efficient nanoparticles in nanomedical application. PEGylation is commonly used
      in nanocarrier for drug delivery, as it confers nanoparticles good stability,
      stealth effect and better targeting specificity compared with those without
      PEGylation. However, the protein binding state on PEGylated AuNP is still limited
      known. In present work, we prepared 13 nm AuNPs and then PEGylated them with
      thiol PEG methoxy. Lysozyme is selected as a model protein and to investigate the
      interactions on protein-PEGylated/AuNP interface. The thermal unfolding processes
      of lysozyme in absence and presence of PEGylated AuNP were measured by
      synchrotron radiation based circular dichroism (SRCD), dynamic light scattering
      (DLS) and infrared spectroscopy (IR). The results suggest that in terms of
      secondary structural changes, alpha helix content is decreased, while beta sheet
      content is increased, and thus the adsorbed lysozyme may be present in PEG layer.

PMID- 29458609
TI  - Prediction of Sliding Friction Coefficient Based on a Novel Hybrid Molecular
      Mechanical Model.
AB  - Sliding friction is a complex phenomenon which arises from the mechanical and
      molecular interactions of asperities when examined in a microscale. To reveal and
      further understand the effects of micro scaled mechanical and molecular
      components of friction coefficient on overall frictional behavior, a hybrid
      molecular-mechanical model is developed to investigate the effects of main
      factors, including different loads and surface roughness values, on the sliding
      friction coefficient in a boundary lubrication condition. Numerical modelling was
      conducted using a deterministic contact model and based on the molecular
      mechanical theory of friction. In the contact model, with given external loads
      and surface topographies, the pressure distribution, real contact area, and
      elastic/plastic deformation of each single asperity contact were calculated. Then
      asperity friction coefficient was predicted by the sum of mechanical and
      molecular components of friction coefficient. The mechanical component was mainly
      determined by the contact width and elastic/plastic deformation, and the
      molecular component was estimated as a function of the contact area and
      interfacial shear stress. Numerical results were compared with experimental
      results and a good agreement was obtained. The model was then used to predict
      friction coefficients in different operating and surface conditions. Numerical
      results explain why applied load has a minimum effect on the friction
      coefficients. They also provide insight into the effect of surface roughness on
      the mechanical and molecular components of friction coefficients. It is revealed
      that the mechanical component dominates the friction coefficient when the surface
      roughness is large (Rq > 0.2 MUm), while the friction coefficient is mainly
      determined by the molecular component when the surface is relatively smooth (Rq <
      0.2 MUm). Furthermore, optimal roughness values for minimizing the friction
      coefficient are recommended.

PMID- 29458610
TI  - Warpage Characteristics and Process Development of Through Silicon Via-Less
      Interconnection Technology.
AB  - In this study, through silicon via (TSV)-less interconnection using the fan-out
      wafer-level-packaging (FO-WLP) technology and a novel redistribution layer (RDL)
      first wafer level packaging are investigated. Since warpage of molded wafer is a
      critical issue and needs to be optimized for process integration, the evaluation
      of the warpage issue on a 12-inch wafer using finite element analysis (FEA) at
      various parameters is presented. Related parameters include geometric dimension
      (such as chip size, chip number, chip thickness, and mold thickness), materials'
      selection and structure optimization. The effect of glass carriers with various
      coefficients of thermal expansion (CTE) is also discussed. Chips are bonded onto
      a 12-inch reconstituted wafer, which includes 2 RDL layers, 3 passivation layers,
      and micro bumps, followed by using epoxy molding compound process. Furthermore,
      an optical surface inspector is adopted to measure the surface profile and the
      results are compared with the results from simulation. In order to examine the
      quality of the TSV-less interconnection structure, electrical measurement is
      conducted and the respective results are presented.

PMID- 29458611
TI  - Preparation of the Pt/CNTs Catalyst and Its Application to the Fabrication of
      Hydrogenated Soybean Oil Containing a Low Content of Trans Fatty Acids Using the
      Solid Polymer Electrolyte Reactor.
AB  - Pt/CNTs were synthesized with an ethylene glycol reduction method, and the
      effects of carboxyl functionalization, ultrasonic power and the concentration of
      chloroplatinic acid on the catalytic activity of Pt/CNTs were investigated. The
      optimal performance of the Pt/CNTs catalyst was obtained when the ultrasonic
      power was 300 W and the concentration of chloroplatinic acid was 40 mg/mL. The
      durability and stability of the Pt/CNTs catalyst were considerably better
      compared to Pt/C, as shown by cyclic voltammetry measurement results. The trans
      fatty acids content of the obtained hydrogenated soybean oil (IV: 108.4 gl2/100 g
      oil) using Pt/CNTs as the cathode catalyst in a solid polymer electrolyte reactor
      was only 1.49%. The IV of hydrogenated soybean oil obtained using CNTs as carrier
      with Pt loading 0.1 mg/cm2 (IV: 108.4 gl2/100 g oil) was lower than carbon with a
      Pt loading of 0.8 mg/cm2 (IV: 109.9 gl2/100 g oil). Thus, to achive the same IV,
      the usage of Pt was much less when carbon nanotubes were selected as catalyst
      carrier compared to traditional carbon carrier. The changes of fatty acid
      components and the hydrogenated selectivity of octadecenoic acid were also
      discussed.

PMID- 29458612
TI  - Enhanced Visible-Light-Responsive Photocatalytic Properties of Bi2MoO6-BiOCl
      Nanoplate Composites.
AB  - Bi2MoO6-BiOCl nanoplate composites were successfully synthesized by a simple
      solvothermal process. The morphology, microstructure and optical properties of
      the as-prepared Bi2MoO6-BiOCl nanocomposites were characterized using
      transmission electron microscopy (TEM), X-ray diffraction (XRD) and UV-Vis
      diffuse reflection spectroscopy (DRS). A noteworthy enhancement in the visible
      light-responsive photocatalytic degradation of RhB was observed over the Bi2MoO6
      BiOCl nanocomposites compared to its individual components. The enhanced
      photocatalytic performance of Bi2MoO6-BiOCl nanocomposites could be attributed to
      the heterojunction interface in the composite, which can both efficiently
      separate photogenerated electron-hole pairs and also restrain the recombination
      of photoinduced charges.

PMID- 29458613
TI  - Controlled Preparation of Co9S8 for Small Molecule Sensing Platform.
AB  - Cobalt sulfides with different atomic ratios were synthesized by two different
      methods. Electrochemical testing was used to compare the prepared cobalt sulfides
      samples, and a series of physical characterizations was carried out. The results
      demonstrated that the better materials had the phase of Co9S8. Furthermore, the
      pompon-like Co9S8 had a larger specific surface area (45.46 m2 g-1), which
      offered more active sites for the detection of hydrogen peroxide and glucose. The
      sensor based on pompon-like Co9S8 displayed a wide linear response ranged from
      1.50 MUM to 8.51 mM, a favorable sensitivity of 20.80 MUA mM-1 cm-2 and a
      detection limit of 0.45 MUM (signal to noise ratio of 3) for hydrogen peroxide.
      Additionally, the sensor also had a linear response ranged from 21.50 MUM to 1.18
      mM, and a higher sensitivity of 185.32 MUA mM-1 cm-2 for glucose. The sensors
      also exhibited excellent performances in selectivity, stability, and
      reproducibility.

PMID- 29458614
TI  - Microstructure and Chemo-Physical Characterizations of Functional Graphene Oxide
      Iron Oxide-Silver Ternary Nanocomposite Synthesized by One-Pot Hydrothermal
      Method.
AB  - In this work, a functional graphene oxide-iron oxide-silver (GO-Fe3O4-Ag) ternary
      nanocomposite was synthesized by using one-pot hydrothermal treatments of mixture
      solutions of silver nitrate (AgNO3), ferrous chloride tetrahydrate (FeCl2 4H2O),
      polyvinylpyrrolidone (PVP), graphene oxide (GO), and ammonium hydroxide solution
      (NH4OH). The systematic effects of synthesis conditions on the microstructure and
      formation of binary and ternary composite systems were studied. Importantly, high
      crystalline GO-Fe3O4-Ag ternary nanomaterials with average sizes of Fe3O4
      particles ~16 nm and of Ag particles ~20 nm were obtained at optimized conditions
      (125  degrees C, 2.5 mM of AgNO3 and 5 mL of NH4OH). Magnetic analysis indicated
      that the saturated magnetization value of Fe3O4-Ag binary composite sample (~73.1
      emu/g) was improved as compared with pure Fe3O4 nanoparticles (~60.6 emu/g),
      while this of GO-Fe3O4-Ag ternary composite sample was about 57.3 emu/g. With
      exhibited advantages of low-cost, high purity and short synthesis time, the
      hydrothermal-synthesized GO-Fe3O4-Ag ternary nanocomposite can be a promising
      candidate for advanced environmental catalyst and biomedical applications.

PMID- 29458615
TI  - An Asymmetric Supercapacitor Based on Activated Porous Carbon Derived from Walnut
      Shells and NiCo2O4 Nanoneedle Arrays Electrodes.
AB  - A facile method was utilized to convert a common biomass of walnut shells into
      activated porous carbon by carbonization and activation with nitricacid
      treatment. The obtained activated carbon (WSs-2) exhibited excellent
      electrochemical performance with high specific capacitance of 137 F . g-1 at 1 A
      . g-1 and super cycling performance of 96% capacitance retention at 5 A . g-1
      after 5000 cycles. In addition, NiCo2O4 nanoneedle arrays with good
      electrochemical properties were successfully prepared by a simple hydrothermal
      method. An aqueous asymmetric supercapacitor (ASC) device based on WSs-2 and
      NiCo2O4 was assembled, which delivered 21 Wh . kg-1 at a power density of 424.5 W
      . kg-1, and maintained 19 Wh . kg-1 at power density of 4254 W . kg-1 as well as
      excellent cycling stability of 99.3% capacitance retention after 5000 cycles at 4
      A . g-1. Through this method, low-cost, environmentally friendly and large-scale
      carbon materials can be fabricated and applied in supercapacitor electrodes.

PMID- 29458616
TI  - Improved Cytotoxic Effect of Doxorubicin by Its Combination with Sclareol in
      Solid Lipid Nanoparticle Suspension.
AB  - This work aims to develop, characterize, and evaluate the anticancer activity of
      solid lipid nanoparticles (SLN) containing doxorubicin (DOX), an antitumoral from
      the antracycline class, and sclareol (SC), a lipophilic labdene diterpene (SLN
      DOX-SC). The SLN were characterized by Differential Scanning Calorimetry (DSC), X
      ray Diffraction (XRD), Small Angle X-ray Diffraction (SAXS), in vitro release,
      transmission electron microscopy, and polarized light microscopy. Evaluation of
      cell viability was performed in two cell cultures: MCF-7 (human breast cancer)
      and 4T1 (murine breast cancer). The SLN showed a size in the range of 128 nm,
      negative zeta potential, DOX encapsulation efficiency (EE) of 99%, and drug
      loading (DL) of 66 mg/g. Characterization of the formulation by DSC, XRD, and
      SAXS revealed the presence of DOX inside the nanoparticles of SLN and suggested
      increased expulsion/release of this drug when associated with SC. The release
      profiles revealed that the SLN-DOX-SC showed controlled release of DOX at pH 7.4
      with enhanced drug release at low pH, useful for cancer treatment. The SLN-DOX-SC
      demonstrated to be more effective than the free DOX against 4T1 cells. So, the
      developed SLN efficiently encapsulate DOX and SC and show good potential as an
      alternative for cancer treatment.

PMID- 29458617
TI  - Deposition of TiO2 Nanoparticles on Porous Polylactic Acid Fibrous Substrates and
      Its Photocatalytic Capability.
AB  - In this work, porous electrospun polylactic acid (PLA) fibers with high specific
      surface area and excellent biodegradability were examined as the support of
      titanium dioxide (TiO2) nanoparticles (NPs). The deposition of TiO2 NPs on porous
      electrospun PLA fibrous substrates was accomplished through the hydrolysis of
      titanium tetra isopropoxide (TTIP) under ultrasonic irradiation, and the effects
      of the TTIP concentrations on structure and property of composite fibers was also
      investigated. The prepared TiO2-deposited PLA composite fibers were characterized
      by X-ray diffraction (XRD), scanning electron microscopy (SEM), High-resolution
      transmission electron microscopy (HRTEM), Brunauer-Emmett-Teller (BET) and
      thermogravimetric analyzer (TGA). The results indicated that the anatase TiO2 NPs
      with an average size of about several tens of nanometers to 200 nm were
      successfully loaded onto surface of porous PLA fibrous substrates. Meanwhile, the
      TiO2 NPs liked a "double-edged sword," overfull deposition of TiO2 NPs had
      negative effect on the properties of composite fibers. Under the optimized
      condition, the TiO2 NPs deposited dispersedly on the surface of PLA fibers
      without severe agglomeration and this structure performed with a high specific
      surface area of 64.8 m2/g, which was 5 times as large as pure PLA nanofibers
      (12.9 m2/g). In addition, the prepared TiO2-loaded composite fibers showed
      satisfactory removal efficiency on MB, the MB concentration decreased about 75%,
      which was remarkably higher than that of pure PLA fibers. Compared with powdery
      TiO2, TiO2-loaded composite fibers showed considerable photocatalytic activity,
      as well as easier operation, confirming this hybrid composite fibers was suitable
      for the easier operated application of TiO2.

PMID- 29458618
TI  - Electrospun Chitosan Nanofiber Membrane for Adsorption of Cu(II) from Aqueous
      Solution: Fabrication, Characterization and Performance.
AB  - The preparation, characterization and application of chitosan (CS) based
      electrospun nanofiber membrane for the adsorptive removal of Cu(II) from water
      were systematically investigated. Homogeneous, porous polyvinyl alcohol (PVA)/CS
      nanofiber membrane with amorphous structure, and average fiber diameter of 49 nm
      was successfully fabricated. The adsorption of Cu(II) onto the positively charged
      PVA/CS nanofiber membrane (pH < 6) was due to chemisorption rather than
      electrostatic adherence, and was highly pH-dependent. The adsorption equilibrium
      of Cu(II) by the PVA/CS nanofiber was established within 120 min, which was much
      faster than that by CS beads, and the adsorption kinetics followed pseudo-second
      order model well (r 2 > 0.995). The adsorption isotherm data were well fitted
      with Langmuir model, and the maximum Cu(II) adsorption capacity of PVA/CS
      nanofiber membrane was 90.3 mg.g-1, which was much higher than that of CS beads.
      The adsorbed Cu(II) formed strong inner-sphere complex with the adsorbent.
      Coexisting cations of iron, lead, cadmium, nickel, calcium, and magnesium have
      insignificant effect on the Cu(II) adsorption, indicating the adsorbent has good
      selectivity for Cu(II) adsorption. FTIR and XPS analysis reveal amine, hydroxyl
      and ether groups are responsible for the Cu(II) adsorption. This work
      demonstrates the electrospun PVA/CS nanofiber membrane is a promising adsorbent
      for heavy metal removals.

PMID- 29458619
TI  - Photocatalytic CO2 Reduction by Mesoporous Polymeric Carbon Nitride
      Photocatalysts.
AB  - In this paper, a sol-gel derived mesoporous polymeric carbon nitride has been
      investigated as a photocatalyst for CO2 photocatalytic reduction. Noble-metal Pt
      nanoparticles were deposited on carbon nitride (sg-CN) in order to investigate
      the performance of both Pt-sg-CN and sg-CN for photocatalytic CO2 reduction.
      Physicochemical properties of prepared nanocomposites were comprehensively
      characterized by using powder XRD, N2 physisorption, UV-Vis DRS, ICP-AES, FTIR,
      solid-state NMR, SEM, TEM and photoelectrochemical measurements. Compared with
      pure sg-CN, the resulting Pt-loaded sg-CN (Pt-sg-CN) exhibited significant
      improvement on the CO2 photocatalytic reduction to CH4 in the presence of water
      vapor at ambient condition under UV irradiation. 1.5 wt.% Pt-loaded sg-CN (Pt-sg
      CN) photocatalyst formed the highest methane yield of 13.9 MUmol/gcat. after 18 h
      of light irradiation, which was almost 2 times and 32 times improvement in
      comparison to pure sg-CN and commercial TiO2 Evonik P25, respectively. The
      substantial photocatalytic activity of Pt-sg-CN photocatalyst for the yield
      product of the CO2 photocatalytic reduction was attributed to the efficient
      interfacial transfer of photogenerated electrons from sg-CN to Pt due to the
      lower Fermi level of Pt in the Pt-sg-CN hybrid heterojunctions as also evidenced
      by photo-electrochemical measurements. This resulted in the reduction of electron
      hole pairs recombination for effective spatial charge separation, consequently
      increasing the photocatalytic efficiency.

PMID- 29458620
TI  - Facile Fabrication of Uniform MFe2O4 (M = Co, Ni, Cu) Hollow Spheres and Their
      Recyclable Superior Catalytic Activity Towards 4-Nitrophenol Reduction.
AB  - We have developed a facile, efficient, economic, and green method to fabricate
      uniform MFe2O4 (M Co, Ni, Cu) hollow spheres by using polyacrylamide (PAM) as an
      additive agent. The as-obtained three types of hollow ferrites are employed to
      catalyze the reductive transformation of nitrophenols to aminophenols, which
      exhibit excellent catalytic activity. The kinetics of the catalytic reaction
      follows the quasi-first order reaction and its rate constant (kapp) values for
      CoFe2O4, NiFe2O4 and CuFe2O4 are calculated to be 1.62, 11.74 and 37.28 min-1,
      respectively. These data are higher than those former reports which using similar
      reactions catalyzed by different nanocatalysts. Among the three catalysts,
      NiFe2O4 and CuFe2O4 can be successfully reused for at least six consecutive
      cycles and have a stable conversion efficiency of about 100%, while CoFe2O4 is
      catalytically inactive after three cycles. The superiority of the catalytic
      reduction of NiFe2O4 and CuFe2O4 may be due to their soft magnetic properties as
      well as their better separation efficiency of the electron-hole pairs. Thus it is
      expected that these two recyclable hollow ferrites will be used commercially in
      the treatment of aromatic nitro compounds in industrial wastewater.

PMID- 29458621
TI  - One-Step Hydrothemal Synthesis of Nitrogen Doped beta-Ga2O3 Nanostructure and Its
      Optical Properties.
AB  - Nitrogen doped beta-Ga2O3 nanostructures were synthesized using a simple one-step
      aqueous approach. The structure and morphology of the nanostructures were
      characterized. Both the GaOOH precursor and beta-Ga2O3 nanostructures showed the
      rod-like morphology. Meanwhile, the beta-Ga2O3 nanostructures were doped with
      nitrogen, which was proved by X-ray photoelectron spectroscopy (XPS),
      photoluminescence (PL) and cathodoluminescence (CL). The results showed nitrogen
      doped one-dimensional beta-Ga2O3 nanostructures were achieved by in situ doping
      while maintaining the morphology. Meanwhile, as a straightforward method, the
      excellent luminescence properties are suitable for application in white-LED
      phosphors and novel optoelectronic devices.

PMID- 29458622
TI  - Highly Transparent Poly(vinyl alcohol)(PVA)/TiO2 Nanocomposite Films with
      Remarkable Photocatalytic Performance and Recyclability.
AB  - Titanium dioxide (TiO2) has been regarded as an efficient photocatalyst for
      degradation of environmental pollutants. However, recovery of TiO2 nanoparticles
      from suspension limits its practical application. Herein, we reported a novel
      highly transparent poly(vinyl alcohol)(PVA)/TiO2 photocatalytic film via in-situ
      growth and solution casting method. TiO2 nanoparticles with average size of 10 nm
      were uniformly dispersed in transparent PVA matrix. The photocatalytic
      performance was investigated by photodegradation of methyl orange (MO) aqueous
      solution under solar light irradiation. PVA/TiO2 photocatalytic film exhibited
      remarkably high photocatalytic activity and excellent recyclable properties
      during multi-cycle use. PVA not only acted as a transparent supports for TiO2,
      but also worked as an efficient holes scavenger. The hydroxyl groups on PVA
      chains played a key role in separation of photo-generated electrons and holes,
      thus increased the photodegradation rate of MO. This work gives an easy and
      reliable way for polymer/TiO2 nanocomposites in practical environmental
      applications.

PMID- 29458623
TI  - Effect of Fluorine Diffusion on Amorphous-InGaZnO-Based Thin-Film Transistors.
AB  - This study investigated the effect of fluorine (F) diffusion from a fluorinated
      siliconnitride passivation layer (SiNX:F-Pa) into amorphous-InGaZnO-based thin
      film transistors (a-IGZO TFTs). The results of thermal desorption spectroscopy
      and secondary ion mass spectrometry revealed that F was introduced into the SiOX
      etch-stopper layer (SiOX-ES) during the deposition of a SiNX:F-Pa, and did not
      originate from desorption of Si-F bonds; and that long annealing times enhanced F
      diffusion from the SiOX-ES layer to the a-IGZO channel. Improvements to the
      performance and threshold-voltage (Vth) negative shift of IGZO TFTs were achieved
      when annealing time increased from 1 h to 3 h; and capacitance-voltage results
      indicated that F acted as a shallow donor near the source side in a-IGZO and
      induced the negative Vth shift. In addition, it was found that when IGZO TFTs
      with SiNX:F-Pa were annealed 4 h, a low-resistance region was formed at the
      backchannel of the TFT, leading to a drastic negative Vth shift.

PMID- 29458624
TI  - Co-Fe Prussian Blue Coordination Polymer Modified Silicon Nanowires Array for
      Efficient Photoelectrochemical Water Oxidation.
AB  - The Co-Fe prussian blue coordination polymer modified Silicon nanowires array
      (SiNW@CoHCF array) exhibits promising behavior in photoelectrochemical (PEC)
      water oxidation, giving rise to a largely enhanced photocurrent density and
      stability, much superior to those of SiNW-based photoanodes. The CoHCF shell as
      effective co-catalyst increases the reaction kinetics, thus depressing the charge
      recombination rate, as well as protects SiNWs array photoanode from
      photocorrosion. It is found that the CoHCF significantly decreases the charge
      transfer impedance (Rct), which means that the CoHCF facilitates majority
      transport and collection. These advantages may account for the performance
      enhancement.

PMID- 29458625
TI  - Facile Synthesis of Graphene Encapsulated Co2SnO4 Nanoparticles as Enhanced Anode
      Materials for Lithium-Ion Batteries.
AB  - A graphene encapsulated Co2SnO4 nanoparticles (Co2SnO4 NPs@rGO) was synthesized
      via the analogous mechanism of electrostatic interactions followed by thermal
      treatment. The Co2SnO4 NPs were uniformly encapsulated in the graphene sheets. As
      an anode material for rechargeable lithium batteries Co2SnO4 NPs@rGO exhibits
      enhanced cyclability and rate performance compared with free Co2SnO4 NPs. Even
      after 200 cycles, it still delivered large reversible capacity of 1037.9 mA h g-1
      at 200 mA g-1. The excellent electrochemical performance should be associated
      with the uniform encapsulation of Co2SnO4 NPs by graphene sheets, which could not
      only effectively buffer the volume expansion and prevent the aggregation of the
      Co2SnO4 NPs but maintain good electrical conductivity of the whole electrode
      during the discharge/charge process.

PMID- 29458626
TI  - Simple Fabrication of Homogeneous ZnO Core/Shell Nanorod Arrays for Ultraviolet
      Photodetectors.
AB  - A simple technique of two-step growth was employed to fabricate homogeneous ZnO
      core/shell nanorod arrays which were composed of ZnO nanodisk shell layer on the
      surface of ZnO nanorod arrays. The ultraviolet (UV) response characteristics of
      the device were measured. The homogeneous ZnO core/shell photodetector had
      remarkably enhanced response and recovery speed compared with pure ZnO nanorod
      arrays. It indicated that surface homogeneous coating can be an alternative
      method to enhance the response and recovery properties of the ZnO nanorod array
      photodetectors.

PMID- 29458627
TI  - Proton-Conducting Polymer Membrane Consisting of Cross-Linked Poly(2-hydroxyethyl
      methacrylate) with Nafion(r) for Fuel Cell Application.
AB  - To increase the water retention and proton-conducting ability of Nafion(r), we
      prepared a cross-linked polymer consisting of poly(2-hydroxyethyl methacrylate)
      (pHEMA) and Nafion(r). pHEMA was chosen as a cross-linking polymer because it
      produces a water-insoluble but water-swellable polymer. Although it is
      hydrophobic, its water-swellable characteristic means that water will not be
      excluded from the polymer. Introduction of pHEMA into Nafion(r) prevents polymer
      solubility and provides structural stability and rigidity, which should in turn
      reduce the methanol permeability. Moreover, convenient permeability of pHEMA to
      cations makes it a good candidate for a hydrocarbon proton-conducting polymer
      tuned with Nafion(r).

PMID- 29458628
TI  - Size-Strain Analysis of Iron-Excess Mn-Zn Ferrite Nanoparticles Using Synchrotron
      Diffraction and Its Correlation with Magnetic Saturation and Isoelectric pH.
AB  - Iron-excess Mn-Zn ferrite nanoparticles were prepared by coprecipitation with
      sodium hydroxide (NaOH) at different concentrations (0.1, 0.2, 0.5 and 1.0
      mol/L). The results of X-ray diffraction (XRD) analysis using Whole Powder
      Pattern Modeling (WPPM) showed that higher concentrations of NaOH promote
      crystallite growth and broader dispersion in crystallite sizes. Energy dispersive
      X-ray spectroscopy indicates that zinc loss is noticeable when [NaOH] >= 0.2
      mol/L. XRD revealed also a significant less-crystalline phase contribution
      alongside the main peaks of the nanocrystalline cubic spinel ferrite phase. The
      less-crystalline fraction is lower for the ferrite obtained with 0.2 mol/L of
      NaOH, being about 50% and more than 70% for the other samples. Despite of the
      less-crystalline fraction and the excess of iron, no secondary phases were
      detected. The Warren curves showed that the concentration of NaOH significantly
      influences the microstrain in the crystallites, being smaller for the sample
      obtained with NaOH at 0.2 mol/L. The sample prepared with this condition
      presented the better properties to be used as magnetic tracer in clinical
      diagnoses combining small mean crystallite size, low microstrain, which resulted
      in materials with higher magnetic saturation and high surface charge under blood
      pH.

PMID- 29458629
TI  - Remarkably Improvement in Antibacterial Activity of Carbon Nanotubes by
      Hybridizing with Silver Nanodots.
AB  - In view of their super capacity of adsorbing microbial, the carbon nanotubes
      (CNTs) were used as the carriers for in situ synthesizing well-dispersed and
      small-sized silver nanodots (AgND), to prepare a new type of antibacterial agent
      with remarkably improved activity. Polyethyleneimine (PEI) was introduced as a
      linkage for guaranteeing the as-generated AgND to be anchored onto the CNTs and
      to prevent them from agglomeration. The obtained hybridizing materials were
      characterized by transmission electron microscopy, X-ray diffraction and X-ray
      photoelectron spectroscopy, and the results showed that the AgND with an average
      size of 2.6 nm were uniformly loaded on surfaces of CNTs. There existed special
      interactions between silver atoms and CNTs. The antibacterial activities of the
      as-prepared hybrids against Escherichia coli were evaluated by disk diffusion
      assay method and minimal inhibitory concentration measurements. The results
      showed that the as-prepared hybrids displayed a remarkable improvement in
      antibacterial activity as compared to CNTs, acidified-CNTs and even the identical
      silver amount of AgNO3 solution, which was mainly attributed to the small size of
      AgND and the hybridizing effect between AgND and CNTs.

PMID- 29458630
TI  - A Mesopore-Dependent Catalytic Cracking of n-Hexane Over Mesoporous
      Nanostructured ZSM-5.
AB  - Herein, pore size, crystalinity, and Si/Al ratio of mesoporous ZSM-5 (MFI)
      nanocrystals was controlled by synthesis parameters, such as surfactant
      concentration ([3-(trimethoxysilyl)propyl] hexa-decyl dimethyl ammonium
      chloride), sodium hydroxide concentrations, synthesis temperature and time. The
      morphology, surface structure and composition of the MFI particles was
      systematically investigated. More notably, the mesopore-dependent catalytic
      activity of ZSM-5 was evaluated by studying the cracking of n-hexane. The
      findings suggest the porosity has pronounced impact on the catalytic activity,
      selectivity and stability of ZSM-5 nanocrystals. Critical surface attributes such
      as nature of acid sites (Bronsted and Lewis), concentration, and strength are
      obtained by the infrared study of adsorbed probe molecules (pyridine) and the
      temperature programmed desorption. In spite of being weaker in Si/Al ratio or
      acidic strength, mesoporous catalysts showed more stable and efficient cracking
      of n-hexane suggesting that acidity seems not the predominant factor operative in
      the activity, selectivity and stability.

PMID- 29458631
TI  - Continuous Preparation of Water-Dispersible Magnetite Nanoparticles by
      Electrochemical Synthesis.
AB  - Highly water-dispersible magnetic nanoparticles were synthesized by convenient
      electrochemical techniques using a continuous flow reactor. The surface
      properties of the magnetic nanoparticles (MNPs) were modified with hydrophilic
      organic ligands during the electrochemical synthesis process to control the
      degree of dispersion in water. The kind of hydrophilic low-molecular weight
      polymers or surfactants influenced the sizes of the particles ranged between 25
      40 nm (in diameter) and their size distribution. Chitosan-modified MNPs exhibited
      the most uniform particle size distribution among the MNPs synthesized in this
      study as well as excellent dispersion stability and magnetic properties in water
      after the crosslinking of the amino groups in chitosan. Especially, the
      dispersion stability of the MNPs in water was systematically investigated via a
      light scattering analysis.

PMID- 29458632
TI  - Zeolite Supported-Nano TiO2 Composites Prepared by a Facile Solid Diffusion
      Process as High Performance Photocatalysts.
AB  - In this paper, zeolite supported-nano TiO2 photocatalytic composites were
      synthesized by an easily-operated solid diffusion process, in which zeolite was
      used as the support matrix. And the microstructures, morphologies and
      photocatalytic properties of the zeolite supported-nano TiO2 composites were
      characterized and analyzed by scanning and transmission electron microscopy, X
      ray photoelectron spectroscopy, UV-visible spectroscopy, fluorescence
      spectroscopy and methylene blue degradation tests. The results showed that
      zeolite matrix reduced agglomeration of nano-TiO2 and enhanced the absorption
      ability within the UV-Vis range, consequently increased the photocatalytic
      activity of the composites. Meanwhile, the influences of TiO2/zeolite proportion
      on their photocatalytic performances were explored, which indicated that 90 wt%
      TiO2/zeolite had optimal photocatalytic capability and stable properties.

PMID- 29458633
TI  - Biomass-Based Carbon Nanofibers Prepared by Electrospinning for Supercapacitor.
AB  - Biomass-based carbon nanofibers were prepared by double-nozzle electrospinning
      the aqueous solution of acid treated the waste medicine Aconitum sinomontanum
      Nakai extraction and poly-acrylonitrile followed by thermal treatment in an inert
      atmosphere. The structural, constituent and surface properties of biomass-based
      carbon nanofibers were investigated by means of spectroscopic, microscopy, energy
      spectrometer and Brunauer-Emmet-Teller (BET) techniques. The results showed that
      the biomass-based carbon nanofibers had abundant pore structure and large
      specific surface area. The electrochemical performance of supercapacitor
      electrodes with the nanofibers was studied. This electrode showed a capacitance
      of 295 F/g at the current density of 1 A/g in 6 mol/L aqueous KOH electrolyte,
      and 98.5% capacity retention after 1000 charge/discharge cycles at the current
      density of 2 A/g. This indicate that the activate biomass-based carbon nanofibers
      have a good electrochemical stability.

PMID- 29458634
TI  - Comparison of Stabilizer Effects on the Size, Dispersion, and Catalytic Property
      of Pt, PtCu, and PtRu Nanoparticles.
AB  - Carbon-supported Pt, Pt-Cu, and Pt-Ru nanoparticles were prepared by an alcohol
      reduction method in the presence of carboxylates and phosphinate in order to
      investigate the role of these stabilizers in the nanoparticle formation process
      and the effect on catalytic properties in 2-propanol oxidation. For the Pt-Cu
      system, long chain carboxylate gave small dispersed particles even with high
      metal loading while phosphinate gave aggregated particles. For the Pt and Pt-Ru
      systems, fewer aggregates were observed and the particle size was independent of
      the chain length of carboxylate while much smaller and dispersed particles were
      obtained with phosphinate. Phosphinate mainly prevents metal crystal growth while
      carboxylates prevent both crystal growth and formation of aggregated particles.
      Although surface poisoning is severe on small dispersed particles in 2-propanol
      oxidation, dehydrogenation of 2-propanol at low potential is little affected.
      Phosphinate-protected catalysts were more tolerant to poisoning promoting 2
      propanol electrooxidation at high potential range. The presence of Cu promoted 2
      propanol electrooxidation at low potential range. These components made
      phosphinate-protected PtCu best perform in 2-propanol oxidation at 30  degrees C.

PMID- 29458635
TI  - Synthesis and Electrochemical Performance of NiCO2S4 as Anode for Lithium-Ion
      Batteries.
AB  - NiCO2S4 with different morphology was controllably fabricated by a facile
      hydrothermal and solvothermal route. The as-obtained samples were analyzed and
      characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS),
      and scanning electron microscopy (SEM). The results reveal that the sample (NCS
      1) prepared by hydrothermal method manifest a mixture of nanorods and
      nanospheres. The sample (NCS-2) synthesized by solvothermal process takes on
      spherical nanoparticles (NPs). It is found that the morphology of the sample has
      much influence on the electrochemical property. When applied as anode for lithium
      ion batteries (LIBs), the NiCO2S4 NPs (NCS-2) possess the highest reversible
      discharge capacity of 1469.8 mAh g-1 compared with other two samples at the
      current density of 100 mA g-1 in the voltage window of 0.01-3 V. Additionally, it
      remains a specific capacity of 1163.7 mAh g-1 at a current density of 100 mAg-1
      after 100 cycles. This excellent electrochemical performance arises from its
      unique mesoporous structure, which can reduce the transport lengths of both
      lithium ions and electrons. The mesoporous NiCO2S4 NPs show the great potential
      development of high-capacity anode materials for LIBs.

PMID- 29458636
TI  - Shape-Control of Three-Dimensional Self-Assembly Graphene by Hydrothermal
      Reaction Time and Its Biological Application.
AB  - In this paper, three-dimensional self-assembly graphene (3D-G) was prepared by
      the hydrothermal synthesis method, and 3D-G was designed as a suitable biological
      scaffold for cell growth and adhesion. The shape of 3D-G was tuned by adjusting
      the hydrothermal reaction time (6 h, 12 h, 18 h and 24 h). Then the scanning
      electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Raman
      spectroscopy and X-ray photoelectron spectroscopy (XPS) analyses were used to
      characterize the microstructure and component of 3D-G, which showed that the
      length, diameter, pore size and defects of 3D-G were all decreased as the
      reaction-time increased. In vitro cell culture experiment, the cytocompatibility
      of 3D-G prepared under different hydrothermal reaction time was assessed using
      mouse fibroblast cells (L929) via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H
      tetrazolium bromide (MTT). Meanwhile, the cell adhesion, growth and proliferation
      were also observed by SEM. These results showed that the 3D-G with the reaction
      time of 24 h (3D-G/24 h) had the best cytocompatibility, which could be used as
      tissue scaffolds for cell growth.

PMID- 29458637
TI  - Controlled Synthesis of Silver Micro/Nano Leaves for Oxygen Reduction and CO2
      Reduction.
AB  - In this study, three different Ag micro/nano leaves were successfully synthesized
      through a galvanic displacement reaction by adjusting the concentration of Ag+.
      The catalytic activities of the prepared Ag micro/nano leaves toward ORR showed
      strong dependence on their morphology. An optimal concentration of Ag+ can result
      in a well-defined Ag micro/nano leaves with both crystallization and surface
      area, which showed the best activity towards ORR in alkaline media. In addition,
      the prepared Ag micro/nano leaves also showed high activity towards CO2
      reduction, which required a potential of -0.8 V versus RHE to selectively convert
      CO2 to CO with the faradaic efficiency at about 20%. Compared with the Ag plate
      at the same overpotential, the FE has increased by 5-fold.

PMID- 29458638
TI  - Bio-Reduction of Graphene Oxide Using Sulfate-Reducing Bacteria and Its
      Implication on Anti-Biocorrosion.
AB  - In this paper, we developed an environmental friendly, cost effective, simple and
      green approach to reduce graphene oxide (GO) by a sulfate-reducing bacterium
      Desulfovibrio desulfuricans. The D. desulfuricans reduces exfoliated GO to
      reduced graphene oxide (rGO) at 25  degrees C in an aqueous solution without any
      toxic and environmentally harmful reducing agents. The rGO was characterized with
      X-ray Diffraction, Fourier Transform Infrared Spectroscopy, Scanning Electron
      Microscopy, Transmission Electron Microscope, X-ray Photoelectron Spectroscopy
      and Raman Spectroscopy. The analysis results showed that rGO had excellent
      properties and multi-layer graphene sheets structure. Furthermore, we
      demonstrated that D. desulfuricans, one of the primary bacteria responsible for
      the biocorrosion of various metals, might reduce GO to rGO on the surface of
      copper and prevented the corrosion of copper, which confirmed that
      electrophoretic deposition of GO on the surface of metals had great potential on
      the anti-biocorrosion applications.

PMID- 29458639
TI  - Investigation of the Extracellular Matrix Effect for the QCM/CCD Cell Activity
      Monitoring System.
AB  - A real-time quartz crystal microbalance (QCM) cell activity monitoring system
      coupled with micro CCD cameras was developed to investigate the cultured cell
      activity, which could measure the viscoelastic characteristics of the cell with
      the QCM and observe the cell morphology changes with CCD camera simultaneously.
      Both the viscoelastic characteristics and the shape of the cultured cell are
      important factors to estimate the cell activity and the cell adhesion. The
      extracellular matrix (ECM) on the surface of the QCM is essential to culture the
      cell stably in the QCM monitoring system. To find the ECM optimization condition,
      the adhesive strength of cultured cells on the ECM modified glass surface was
      measured by using rotating water stream and CCD camera. After culturing HepG2
      cells for 24 hours on the ECM modified glass plates, the glass plates were dipped
      in the PBS solution and rotated with 1,000, 1,300, and 1,500 rpm for 30 seconds.
      The adhesiveness of ECMs was investigated by calculating the remained cells after
      rotating. Four types of ECM, such as amino group, carboxyl group, collagen
      monomer, and collagen polymer, were used and tested. The current paper improves
      the sensing system of previous report so that measurements of four ECMs can be
      simultaneously conducted under the same conditions in order to enhance
      reliability. A collagen polymer exposed ECM was the most stable on an
      adhesiveness point of view, but not suitable for the QCM cell activity monitoring
      due to the decrease of the QCM sensitivity. The sensitivity of the QCM cell
      activity monitoring system using collagen monomer as ECM is about 2.6 times
      better than that using collagen polymer. A collagen monomer exposed ECM was more
      stable than amino group and carboxyl group exposed ECMs based on an adhesiveness
      point of view. Therefore, a collagen monomer exposed ECM was the most stable and
      suitable for the QCM cell activity monitoring system among the four ECMs. The
      changes of the resonance frequency and the resonance resistance of the ECM film
      with the cultured cells were investigated and compared the results of CCD camera
      images. From these results, we showed the QCM cell activity monitoring system
      coupled with the micro CCD camera could be applied to the evaluation of the cell
      activities.

PMID- 29458640
TI  - Defect Related Green-Red Luminescence of Sb-Doped ZnO Nanorods Grown by Vapor
      Phase Oxidation Method.
AB  - Vertically aligned undoped and Sb-doped ZnO (ZnSbO) nanorods were grown by the
      vapor-phase oxidation process on sapphire substrates at 700  degrees C using Fe
      as the catalyst. The effect of Sb doping on surface morphology, structural and
      optical properties of ZnO were studied. The grown undoped and Sb-doped ZnO
      nanorods have a hexagonal wurtzite structure with preferential c-axis
      orientation. The as-grown nanorods morphology has shown length of 2-5 MUm and a
      diameter of 100-250 nm. An elongated nanorods and high aspect ratio was observed
      in Sb-doped ZnO. The undoped ZnO nanorods showed a strong and sharp ultraviolet
      (UV) emission centered at ~381 nm, whereas Sb-doped ZnO nanorods exhibited two
      defect related emissions centered at ~530 nm (green) and ~630 nm (red) with a
      suppressed UV emission. The dominance of the red emission in the nanorods
      indicates that it exhibits a much higher defect caused by the Sb doping.

PMID- 29458641
TI  - Bio-Directed Synthesis of Calcium Oxide (CaO) Nanoparticles Extracted from
      Limestone Using Honey.
AB  - Calcium oxide (CaO) nanoparticles have been synthesized by two step thermal
      decomposition method under ambient temperature. Structural analysis was carried
      out by powder X-ray diffraction method and the crystallite size of CaO
      nanoparticles was calculated using Scherrer formula. Fourier transform infrared
      spectroscopy (FTIR) analysis has been carried to identify the functional groups
      present in the synthesized specimen. Optical absorption studies reveal very low
      absorption in the entire visible region. The surface analysis of the synthesized
      particles was analysed using scanning electron microscope (SEM).

PMID- 29458642
TI  - Preparation of CeO2-Quantum Dots/Cu2O Nanocomposites with Enhanced Photocatalytic
      Properties.
AB  - To improve the efficiency of photocatalysts, a composite of CeO2-quantum
      dots/Cu2O (CeO2-QDs/Cu2O) was prepared through a one-step hydrothermal procedure
      in alkaline carbonate solution with Cu2(OH)2CO3 and Ce(NO3)3. 6H2O as precursors
      and glucose as reducing agent. The morphologies and structures of the prepared
      photocatalysts were well characterized utilizing Transmission Electron Microscopy
      (TEM), X-ray Diffractometry (XRD), X-ray Photoelectron Spectroscopy (XPS) and UV
      Vis Diffuse Reflectance Spectrophotometer (DRS). The results indicated that the
      CeO2-QDs with 5 to 10 nm diameters were well dispersed and had a good contact
      with Cu2O. As observed in the photocatalytic experiments, Rhodamine B could be
      degraded more effectively under simulated sunlight using CeO2-QDs/Cu2O as the
      photocatalysts. Also, the obtained photocatalytic kinetics constant was higher
      than that in the experiments using CeO2 or Cu2O nano particles as photocatalysts.
      The enhanced photocatalytic activities might be attributed to the efficient
      separation of photo-generated charge carriers with the help of the p-n
      heterojunction and the morphology of quantum dots.

PMID- 29458643
TI  - Multilayer Nanoporous Graphene as a Water Purification Membrane.
AB  - Porous graphene sheets can be considered as an ultrathin membrane in reverse
      osmosis water desalination processes. In this paper, employing the molecular
      dynamics simulation method, the performance of multilayer porous graphene
      membranes with different pore sizes, layer separation, and layer number were
      investigated. We found that salt rejection and water flux through the membrane
      significantly depend on the graphene pore size and number of graphene layers, and
      controlling these parameters could improve the filtration process. It was shown
      that our 2-layer designed graphene membranes with the pore radius of 3.3 A and
      layer separation of 20 A, can reject more than 86% of ions. Also, no filtration
      process had occurred for graphene layer separation less than 5 A. The results of
      this study that are described by ion hydration radius and water velocity
      distributions can be used to improve the knowledge of water desalination at the
      molecular level, which leads to design more efficient multilayer graphene
      membranes for water purification.

PMID- 29458644
TI  - Recycling of Waste Poly(ethylene terephthalate) Bottles by Alkaline Hydrolysis
      and Recovery of Pure Nanospindle-Shaped Terephthalic Acid.
AB  - Poly(ethylene terephthalate) (PET) is a versatile engineering plastic which
      exhibits exceptional mechanical and thermal properties. Huge amounts of PET are
      consumed in various industries such as food packaging industry, textile industry,
      in the manufacturing of audio, video tapes and X-ray films and so on. But due to
      its substantial fraction by volume in water bodies and its high persistence to
      the atmospheric and biological agents, it could be considered as a hazard
      substance. Thereby chemical recycling of PET serves as a solution to solid waste
      problem as it transforms PET into its monomers via hydrolysis. Chemical recycling
      of post consumed waste PET bottles via alkaline hydrolysis is the main aim of
      this paper. Operating parameters such as reaction time and temperature were
      optimized for the conversion of PET into nanospindle-shaped terephthalic acid
      (TPA). Depolymerization of PET was carried out via alkaline hydrolysis by varying
      reaction time and temperature and maximum yield of 92% was obtained at 200 
      degrees C with reaction time of 25 minutes. The formed TPA nanospindles were
      further characterized in detail which exhibited high crystallinity, purity and
      fascinating thermal and surface properties.

PMID- 29458645
TI  - Preparation of Well-Aligned TiO2 Nanotubes with High Length-Diameter Aspect Ratio
      by Anodic Oxidation Method.
AB  - This paper focused on the influence of various oxidation parameters such as
      electrolyte composition, reaction time, calcination temperature and current
      change on the morphology and structure of TiO2 nanotube arrays. It was found that
      ammonium fluoride with a high viscosity reduced the diffusion rate of fluoride
      ions and significantly increased the length of TiO2 nanotubes, creating nanotubes
      with ordered arrays and uniform diameters. Meanwhile, the time of anodic
      oxidation determined the length of TiO2 nanotube arrays. Well-aligned nanotube
      arrays could be obtained after 0.5-2.5 h of oxidation. In addition, when the
      oxidation temperature was about 30  degrees C, the TiO2 nanotube arrays achieved
      the optimal uniformity and the maximum length-diameter aspect ratio. The
      morphology and quality of the TiO2 nanotubes fabricated were estimated through
      current as a function of reaction time. Consequently, formation mechanism of TiO2
      nanotube arrays was investigated undergoing three major periods. The findings of
      this study can shed some light on the optimal conditions for preparing well
      aligned TiO2 nanotube arrays with high length-diameter aspect ratio.

PMID- 29458646
TI  - CO2 Separation Membranes Consisting of Ionic Liquid/CdO Composites.
AB  - CdO nanoparticles were utilized in the fabrication of a composite membrane
      containing the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate
      (BMIM+BF-4) for CO2 separation. The use of BMIM+BF-4containing CdO nanoparticles
      as a CO2 separator greatly improved separation performance. The ideal selectivity
      for CO2/N2 was 32.5 with a CO2 permeance of 57.1 GPU when CdO 4 liquid. The
      enhanced separation performance nanoparticles were incorporated into the BMIM+BF
      4and the was attributed to increased CO2 solubility facilitated by both the free
      ions in BMIM+BF-4 oxide layer of the CdO nanoparticle. The CdO nanoparticles were
      identified with transmission electron microscopy and the physical and chemical
      properties of the membranes were investigated using scanning electron microscopy,
      Raman spectroscopy and TGA. Interestingly, we found a correlation between CO2
      permeance and electronegativity differences between the metal and oxygen for CO2
      separation membrane. The electronegativity differences between the metal and
      oxygen was ZnO (1.79) > CdO (1.75) > CuO (1.54) > AgO (1.51). The order of CO2
      permeance was ZnO in BMIM+BF-4 (101 GPU) > CdO in BMIM+BF-4 (57.1 GPU) > CuO in
      BMIM+BF-4 (52.4 GPU) > AgO in BMIM+BF-4 (14.1 GPU).

PMID- 29458647
TI  - Highly Uniform Hollow GdF3 Ellipsoids: Controllable Synthesis, Characterization
      and Up-Conversion Luminescence Properties.
AB  - In this paper, the hollow GdF3 ellipsoids were successfully synthesized through a
      facile hydrothermal approach. The results indicated that the as-obtained GdF3
      sample has an orthorhombic structure and the average length and diameter of the
      hollow ellipsoids are 750 nm and 350 nm, respectively. The possible formation
      mechanism of the hollow GdF3 ellipsoids has been presented. The upconversion (UC)
      luminescence properties of the hollow GdF3: Yb3+/Ln3+ (Ln3+ = Er3+, Tm3+, Ho3+)
      ellipsoids were systematically investigated, which showed green (Er3+, 4S3/2,
      2H11/2 -> 4I15/2), blue (Tm3+, 1G4 -> 3H6), and green (Ho3+, 5S2 -> 5I8)
      luminescence under 980 nm NIR excitation, respectively. Furthermore, the UC white
      light was successfully obtained in the GdF3: Yb3+/Er3+/Tm3+ sample through
      adjusting relative doping concentration of Yb3+, Er3+ and Tm3+ ions. These
      findings may reveal potential applications in the fields of laser, bioanalysis,
      optoelectronic and nanoscale devices due to multicolor emissions in the visible
      region.

PMID- 29458648
TI  - In-Situ Scanning Electron Microscopy of Individual Carbon
      Nanotetrahedron/Nanoribbon Structures Under a Tensile Load.
AB  - Flattening of a carbon nanotube with a switching of the flattening direction
      results in the formation of a nanotetrahedron/nanoribbon structure. In this
      study, behavior of individual carbon nanotetra-hedron/nanoribbon structures under
      a tensile load is observed by means of in-situ scanning electron microscopy using
      micro-manipulators. Positions of breakage caused by a tensile load are not
      necessarily at a nanotetrahedron/nanoribbon junction. The results indicate that
      the nanotetrahedron/nanoribbon junctions are not mechanical weak points under a
      tensile load, and the nanotetra-hedron/nanoribbon structures are as strong as
      simple multi-walled carbon nanotubes. In addition, the nanostructures maintain
      their shape and do not transformed to a tubular form.

PMID- 29458649
TI  - Synthesis of PbS and Ag2S Nanorods via Polyol Process.
AB  - PbS and Ag2S nanorods have been synthesized using a polyol process in the
      presence of poly(vinylpyrrolidone) (PVP). First, the production of Pb or Ag was
      realized via the thermal decomposition of a lead/silver salt. Then the Pb or Ag
      precursor was directly combined with S power under heating, leading to the
      formation of the final products. The samples were characterized by X-ray powder
      diffraction (XRD), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS). PbS cubes and
      cubes with a hole in the center were prepared under different reaction
      conditions. Possible formation mechanisms of different PbS or Ag2S morphologies
      have briefly been discussed.

PMID- 29458650
TI  - Utilization of Nano-SiO2 as a Supporting Material for Immobilization of Porcine
      Pancreatic Lipase.
AB  - Nano-SiO2 is an inexpensive material for enzyme immobilization and has been
      frequently utilized for this purpose. In addition to its low cost, Nano-SiO2 has
      several advantages when used as a supporting material, including its lack of
      toxicity and chemical reactivity, allowing easy fixation of enzymes. In this
      article, Porcine Pancreatic lipase was non-covalently immobilized on Nano-SiO2.
      The properties of immobilized enzyme were then defined. The optimum pH and
      temperature for the immobilized PPL for hydrolysis of olive oil were determined
      as 7.6 and 40-50  degrees C, respectively. The immobilized enzyme possessed high
      stability in batch operation; with 73.5% of the initial activity still remaining
      after 8 times of repeated operation of the immobilized lipase. The immobilized
      enzyme was more stable than free enzyme and t1/2 was 25 d, while free lipase
      activity was lost 50% in 2 days. The apparent Km for the immobilized enzyme was
      significantly smaller than that of the free one.

PMID- 29458651
TI  - Odd-Even Effect in Synthesis of Mesoporous Silica Using Long-Chain Acyl-L-Alanine
      Sodium Salt Templating.
AB  - In this research, hexagonal and cubic mesoporous silica with ordered parallel
      pore channels was synthesized using odd chain-length N-undecanoyl-L-alanine
      sodium salt and even chain-length N-lauroyl-L-alanine sodium salt as template
      respectively. Aminopropylsiloxane was used as the co-structure-directing agents
      (CSDA). The ordered mesostructure was characterized by infrared spectroscopy,
      small X-ray diffraction patterns (XRD), scanning electron microscope (SEM),
      trasmission electron microscope (TEM), and nitrogen sorption analysis. The
      results indicated that mesoporous silica which was prepared by asymmetric odd
      chain-length surfactants presented a looser strucuture with large volume than
      mesoporous silica prepared by the even chain-length surfactant. It led to the
      transformation from 2D hexagonal (p6mm) phase to cubic (Ia-3d) mesophase.

PMID- 29458652
TI  - Morphology Control of Eu-Doped Amorphous Gehlenite Phosphors Prepared by Spray
      Pyrolysis.
AB  - Eu-doped amorphous gehlenite phosphors with various morphologies were synthesized
      using spray pyrolysis. Along with un-treated precursor, two commonly used pore
      forming agents, polyethylene glycol and hydrogen peroxide, were applied to
      achieve porous and hollow particle structures. The phase compositions, surface
      morphologies, inner structures and photoluminescence properties of the resulting
      phosphors were examined by X-ray diffraction, scanning electron microscopy,
      transmission electron microscopy and fluorescence spectrometry. The results
      showed that the morphologies of the particles were well-controlled, and a
      correlation between morphology and photoluminescence properties was established.

PMID- 29458653
TI  - Does the Abiotic Formation of Oligopeptides on TiO2 Nanoparticles Require Special
      Catalytic Sites? Apparently Not.
AB  - The oligomerization of non-activated amino acids catalyzed by nanostrucrured
      mineral oxide surfaces holds promises as a sustainable route for the industrial
      production of polypeptides. To analyze the influence of the surface type on the
      catalytic process, we performed, via a mild Chemical Vapor Deposition approach,
      the oligomerization of Glycine on two samples of TiO2 nanoparticles characterized
      by different relative amounts of defective surface terminations. Based on
      infrared spectroscopy and mass spectrometry data, we show herein that the
      formation of peptide bonds on titania nanoparticles does not require highly
      energetic surface terminations, but can occur also on the most abundant and
      thermodynamically most stable {101} facets of nanosized anatase.

PMID- 29458655
TI  - DL-endopeptidases function as both cell wall hydrolases and poly-gamma-glutamic
      acid hydrolases.
AB  - Biopolymers on the cell surface are very important for protecting microorganisms
      from environmental stresses, as well as storing nutrients and minerals. Synthesis
      of biopolymers is well studied, while studies on the modification and degradation
      processes of biopolymers are limited. One of these biopolymers, poly-gamma
      glutamic acid (gamma-PGA), is produced by Bacillus species. Bacillus subtilis
      PgdS, possessing three NlpC/P60 domains, hydrolyses gamma-PGA. Here, we have
      demonstrated that several dl-endopeptidases with an NlpC/P60 domain (LytE, LytF,
      CwlS, CwlO, and CwlT) in B. subtilis digest not only an amide bond of d-gamma
      glutamyl-diaminopimelic acid in peptidoglycans but also linkages of gamma-PGA
      produced by B. subtilis. The hydrolase activity of dl-endopeptidases towards
      gamma-PGA was inhibited by IseA, which also inhibits their hydrolase activity
      towards peptidoglycans, while the hydrolysis of PgdS towards gamma-PGA was not
      inhibited. PgdS hydrolysed only the d-/l-Glu-d-Glu linkages of d-Glu-rich gamma
      PGA (d-Glu:l-Glu=7 : 3) and l-Glu-rich gamma-PGA (d-Glu:l-Glu=1 : 9), indicating
      that PgdS can hydrolyse only restricted substrates. On the other hand, the dl
      endopeptidases in B. subtilis cleaved d-/l-Glu-d-/l-Glu linkages of d-Glu-rich
      gamma-PGA (d-Glu:l-Glu=7 : 3), indicating that these enzymes show different
      substrate specificities. Thus, the dl-endopeptidases digest gamma-PGA more
      flexibly than PgdS, even though they are annotated as "dl-endopeptidase,
      digesting the d-gamma-glutamyl-diaminopimelic acid linkage (d-l amino acid
      bond)".

PMID- 29458654
TI  - Identification and characterization of viral defective RNA genomes in influenza B
      virus.
AB  - Influenza B virus (FLUBV) is an important pathogen that infects humans and causes
      seasonal influenza epidemics. To date, little is known about defective genomes of
      FLUBV and their roles in viral replication. In this study, by using a next
      generation sequencing approach, we analyzed total mRNAs extracted from A549 cells
      infected with B/Brisbane/60/2008 virus (Victoria lineage), and identified four
      defective FLUBV genomes with two (PB1?A and PB1?B) from the polymerase basic
      subunit 1 (PB1) segment and the other two (M?A and M?B) from the matrix (M)
      protein-encoding segment. These defective genomes contained significant deletions
      in the central regions with each having the potential for encoding a novel
      polypeptide. Significantly, each of the discovered defective RNAs can potently
      inhibit the replication of B/Yamanashi/166/98 (Yamagata lineage). Furthermore,
      PB1?A was able to interfere modestly with influenza A virus (FLUAV) replication.
      In summary, our study provides important initial insights into FLUBV defective
      interfering genomes, which can be further explored to achieve better
      understanding of the replication, pathogenesis and evolution of FLUBV.

PMID- 29458656
TI  - Stress responses, outer membrane permeability control and antimicrobial
      resistance in Enterobacteriaceae.
AB  - Bacteria have evolved several strategies to survive a myriad of harmful
      conditions in the environment and in hosts. In Gram-negative bacteria, responses
      to nutrient limitation, oxidative or nitrosative stress, envelope stress,
      exposure to antimicrobials and other growth-limiting stresses have been linked to
      the development of antimicrobial resistance. This results from the activation of
      protective changes to cell physiology (decreased outer membrane permeability),
      resistance transporters (drug efflux pumps), resistant lifestyles (biofilms,
      persistence) and/or resistance mutations (target mutations, production of
      antibiotic modification/degradation enzymes). In targeting and interfering with
      essential physiological mechanisms, antimicrobials themselves are considered as
      stresses to which protective responses have also evolved. In this review, we
      focus on envelope stress responses that affect the expression of outer membrane
      porins and their impact on antimicrobial resistance. We also discuss evidences
      that indicate the role of antimicrobials as signaling molecules in activating
      envelope stress responses.

PMID- 29458657
TI  - Digestion of peptidoglycan near the cross-link is necessary for the growth of
      Bacillus subtilis.
AB  - Bacterial cells are covered with peptidoglycan (PG) layer(s), serving as the
      cellular exoskeleton. The PG sacculus changes its shape during cell growth, and
      thus both the synthesis and disassembly of PG are important for cell
      proliferation. In Bacillus subtilis, four dl-endopeptidases (DLEPases; LytE,
      LytF, CwlO and CwlS) are involved in the maintenance of cell morphology. The lytE
      cwlO double mutant exhibits synthetic lethality and defective cell elongation,
      while the lytE lytF cwlS triple mutant exhibits defective cell separation, albeit
      with septum formation. LytE is involved in both cell separation and elongation.
      We propose that DLEPases have varied roles in cell separation and elongation. To
      determine these roles, the catalytic domain of LytE was substituted with another
      catalytic domain that digests the other bonds in PG. By using the chimeric
      enzymes, we assessed the suppression of the synthetic lethality by the cell
      elongation defect and the disruption of chain morphology by the cell separation
      defect. All the constructed chimeric enzymes suppressed the cell separation
      defect, restoring the chain morphology. Digestion at any position of PG broke the
      linkage between two daughter cells, releasing them from each other. However, only
      d,d-endopeptidases suppressed the lack of DLEPase in the lytE cwlO double mutant.
      This indicated that the release of tension on the expanding PG sacculus is not
      the sole essential function of DLEPases. Considering that the structure of the
      digested PG is important for cell elongation, the digested product might be
      reused in the growth process in some way.

PMID- 29458658
TI  - Halomonas saliphila sp. nov., a moderately halophilic bacterium isolated from a
      saline soil.
AB  - A novel, Gram-stain-negative, aerobic, rod-shaped, motile and moderately
      halophilic bacterium, designated strain LCB169T, was isolated from a saline soil
      sample from Gansu Province, PR China. The cells of LCB169T grew at 10-52  degrees
      C (optimum 30  degrees C), at pH 6.0-10.0 (optimum pH 8.0) and in the presence of
      0-17 % (w/v) NaCl (optimum 10-15 %). Phylogenetic analysis based on 16S rRNA gene
      sequences and concatenated 16S rRNA, gyrB and rpoD genes sequences revealed that
      LCB169T represented a member of the genus Halomonas in the class
      Gammaproteobacteria. The most closely related species were Halomonas daqingensis
      DQD2-30T (98.0 % 16S rRNA gene sequence similarity), Halomonas kenyensis AIR-2T
      (97.8 %) and Halomonas desiderata FB2T (97.5 %). DNA-DNA relatedness values
      between LCB169T and H. daqingensis CGMCC 1.6443T, H. desiderata DSM 9502T and H.
      kenyensis DSM 17331T were 33, 35 and 38 %, respectively. The polar lipids were
      identified as diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylcholine and three unidentified
      phospholipids. The major fatty acids were C18 : 1omega7c, C16 : 0, C16 : 1omega7c
      and C12 : 0 3-OH. The genomic DNA G+C content was 66.1 mol% and the predominant
      respiratory quinone was Q-9. On the basis of the results of phenotypic,
      phylogenetic and chemotaxonomic analyses and DNA-DNA hybridization relatedness
      values, LCB169T is considered to represent a novel species of the genus
      Halomonas, for which the name Halomonas saliphila sp. nov. is proposed. The type
      strain is LCB169T (=CGMCC 1.15818T=KCTC 52618T).

PMID- 29458660
TI  - Identification of antigenic proteins from Mycobacterium avium subspecies
      paratuberculosis cell envelope by comparative proteomic analysis.
AB  - Johne's disease (JD) is a contagious, chronic granulomatous enteritis of
      ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The aim of
      this study was to identify antigenic proteins from the MAP cell envelope (i.e.
      cell wall and cytoplasmic membranes) by comparing MAP, M. avium subsp.
      hominissuis (MAH) and M. smegmatis (MS) cell envelope protein profiles using a
      proteomic approach. Composite two-dimensional (2D) difference gel electrophoresis
      images revealed 13 spots present only in the image of the MAP cell envelope
      proteins. Using serum from MAP-infected cattle, immunoblot analysis of 2D gels
      revealed that proteins in the 13 spots were antigenic. These proteins were
      identified by liquid chromatography tandem mass spectrometry as products of the
      following genes: sdhA, fadE25_2, mkl, citA, gapdh, fadE3_2, moxR1, mmp, purC,
      mdh, atpG, fbpB and desA2 as well as two proteins without gene names identified
      as transcriptional regulator (MAP0035) protein and hypothetical protein
      (MAP1233). Protein functions ranged from energy generation, cell wall
      biosynthesis, protein maturation, bacterial replication and invasion of
      epithelial cells, functions considered essential to MAP virulence and
      intracellular survival. Five MAP cell envelope proteins, i.e. SdhA, FadE25_2,
      FadE3_2, MAP0035 and DesA2 were recombinantly expressed, three of which, i.e.
      SdhA, FadE25_2 and DesA2, were of sufficient purity and yield to generate
      polyclonal antibodies. Immunoblot analysis revealed antibodies reacted
      specifically to the respective MAP cell envelope proteins with minimal cross
      reactivity with MAH and MS cell envelope proteins. Identification and
      characterization of MAP-specific proteins and antibodies to those proteins may be
      useful in developing new diagnostic tests for JD diagnosis.

PMID- 29458659
TI  - Relationship of environmental disturbances and the infectious potential of fungi.
AB  - Fungi are critical organisms for the environment and offer many benefits to
      modern society through their application in the pharmaceutical, beverage and food
      industries. In contrast, fungal pathogens are emerging threats to humans,
      animals, plants and insects with potential to cause devastating mortality,
      morbidity and economic loss. Outbreaks associated with anthropogenic alterations
      of the environment, including climate change-related events such as natural
      disasters, are responsible for human, animal and plant disease. Similarly, fungi
      and their metabolites also have a negative impact in agriculture, posing a
      serious threat to our food supplies. Here, we describe the existing knowledge and
      importance of understanding the relationship of fungi and the environment in the
      context of human, animal and plant disease. Our goal is to encourage
      communication between scientists and the general public to create informed
      awareness about the impact of fungi in their daily lives and their environment.

PMID- 29458661
TI  - Chicken astrovirus as an aetiological agent of runting-stunting syndrome in
      broiler chickens.
AB  - Despite descriptions of runting-stunting syndrome (RSS) in broiler chickens
      dating back over 40 years, the aetiology has not yet been described. A novel
      chicken astrovirus (CkAstV) was isolated in an LMH liver cell line from the
      intestines of chickens affected with RSS. Clinical RSS is characterized by
      retarded growth and cystic crypt lesions in the small intestine. In 1-day-old
      broiler chickens infected with the CkAstV isolate, virus was only detected in the
      intestinal epithelial cells during the first few days after infection. Notably,
      the preferred host cells are the crypt epithelial cells following initial
      replication in the villous epithelial cells, thus implying viral preference for
      immature intestinal cells. Nevertheless, the CkAstV isolate did not induce
      remarkable pathological changes, despite the presence of the virus in situ.
      Serial chicken-to-chicken passages of the virus induced increased virulence, as
      displayed by decreased weight gain and the presence of cystic lesions in the
      small intestine reproducing clinical RSS in chickens. The analysis of the full
      length genome sequences from the isolated CkAstV and the CkAstV from the bird-to
      bird passages showed >99 % similarity. The data obtained in this study suggest
      that the CkAstV isolate is capable of inducing RSS following serial bird-to-bird
      passages in broilers and is as an aetiological agent of the disease.

PMID- 29458662
TI  - Spirosoma horti sp. nov., isolated from apple orchard soil.
AB  - A Gram-negative, motile by gliding, rod-shaped, aerobic bacterium, designated S7
      3-19T, was isolated from apple orchard soil in Gyeongsangnam-do Province,
      Republic of Korea, and characterized taxonomically by using a polyphasic
      approach. Phylogenetic analysis based on 16S rRNA gene sequencing showed that
      strain S7-3-19T belonged to the family Cytophagaceae and was most closely related
      to Spirosoma linguale DSM 74T (96.38 %), Spirosoma fluviale MSd3T (96.38 %),
      Spirosoma pulveris JSH5-14T (96.35 %) and Spirosoma radiotolerans DG5AT (96.24
      %). Chemotaxonomic characteristics supported the classification of strain S7-3
      19T within the genus Spirosoma. Summed feature 3 (C16 : 1omega7c/C16 : 1omega6c;
      46.7 %) and C16 : 1omega5c (23.8 %) were the major fatty acids.
      Phosphatidylethanolamine, an unidentified aminophospholipid, an unidentified
      phospholipid and two unidentified lipids were the major polar lipids. Menaquinone
      with seven isoprene units was the predominant respiratory quinone. The G+C
      content of the genomic DNA of strain S7-3-19T was 48.6 mol%. On the basis of its
      phenotypic properties, genotypic distinctiveness and chemotaxonomic features,
      strain S7-3-19T represents a novel species of the genus Spirosoma, for which the
      name Spirosomahorti sp. nov. is proposed. The type strain is S7-3-19T (=KCTC
      52728T=JCM 32131T).

PMID- 29458663
TI  - Cytochromes in anaerobic growth of Acidithiobacillus ferrooxidans.
AB  - The mineral sulfide-oxidising Acidithiobacillus ferrooxidans has been extensively
      studied over many years but some fundamental aspects of its metabolism remain
      uncertain, particularly with regard to its anaerobic oxidation of sulfur. This
      label-free, liquid chromatography-electron spray ionisation-mass spectrometry
      based proteomic analysis estimated relative protein abundance during aerobic and
      anaerobic growth of At. ferrooxidans. One of its two bc1 complexes, that encoded
      by the petII operon, was strongly implicated in anaerobic ferric iron-coupled
      sulfur oxidation, probably in conjunction with two cytochromes. These two
      cytochromes are homologs of the Cyc2 and Cyc1 proteins that are involved in
      ferrous iron oxidation. The previously undetected cytochromes apparently
      associated with anaerobic growth in At. ferrooxidans appear to be absent in many
      other ferrous iron-oxidising acidophiles that can also reduce ferric iron, which
      suggests a diversity in the ferric-iron-coupled sulfur oxidation pathways. For
      aerobic growth of At. ferrooxidans, this analysis was consistent with the
      generally accepted mechanism for its oxidation of ferrous iron. Unexpectedly,
      proteins encoded by the petI operon were not abundant and generally not detected
      in the proteomic analyses of cells grown aerobically on sulfur, although there
      was some expression of genes of the petI and petII operons in these cells.

PMID- 29458664
TI  - Loving the poison: the methylcitrate cycle and bacterial pathogenesis.
AB  - Propionate is an abundant catabolite in nature and represents a rich potential
      source of carbon for the organisms that can utilize it. However, propionate and
      propionate-derived catabolites are also toxic to cells, so propionate catabolism
      can alternatively be viewed as a detoxification mechanism. In this review, we
      summarize recent progress made in understanding how prokaryotes catabolize
      propionic acid, how these pathways are regulated and how they might be exploited
      to develop novel antibacterial interventions.

PMID- 29458665
TI  - Death and gastrointestinal bleeding complicate encephalomyelitis in mice with
      delayed appearance of CNS IgM after intranasal alphavirus infection.
AB  - Central nervous system (CNS) infection of C57BL/6 mice with the TE strain of
      Sindbis virus (SINV) provides a valuable animal model for studying the
      pathogenesis of alphavirus encephalomyelitis. While SINV TE inoculated
      intracranially causes little mortality, 20-30 % of mice inoculated intranasally
      (IN) died 8 to 11 days after infection, the period during which immune cells
      typically infiltrate the brain and clear infectious virus. To examine the
      mechanism behind the mortality, mice infected IN with SINV TE were monitored for
      evidence of neurological disease, and those with signs of severe disease
      (moribund) were sacrificed and tissues collected. Mice showing the usual mild
      signs of encephalomyelitis were concurrently sacrificed to serve as time-matched
      controls (sick). Sixty-eight per cent of the moribund mice, but none of the sick
      mice, showed upper gastrointestinal bleeding due to gastric ulceration. Clinical
      disease and gastrointestinal pathology could not be attributed to direct viral
      infection of tissues outside of the CNS, and brain pathology and inflammation
      were comparable in sick and moribund mice. However, more SINV antigen was present
      in the brains of moribund mice, and clearance of infectious virus from the CNS
      was delayed compared to sick mice. Lower levels of SINV-specific IgM and fewer
      B220+ B cells were present in the brains of moribund mice compared to sick mice,
      despite similar levels of antiviral IgM and IgG in serum. These findings
      highlight the importance of the local antibody response in determining the
      outcome of viral encephalomyelitis and offer a model system for understanding
      individual variation in this response.

PMID- 29458666
TI  - Saccharopolyspora deserti sp. nov., a novel halotolerant actinobacterium isolated
      from a desert.
AB  - Strain SYSU D8010T was isolated from a desert sand sample collected in Saudi
      Arabia. The taxonomic position of the isolate was investigated by the polyphasic
      taxonomic approach. The isolate was found to be Gram-positive and aerobic. The
      strain was able to grow at 14-40  degrees C, pH 5.0-9.0 and in the presence of up
      to 22 % (w/v) NaCl. Strain SYSU D8010T contained meso-diaminopimelic acid as cell
      wall diamino acid, and arabinose, fucose, galactose, glucose and rhamnose as the
      whole-cell sugars. The primary polar lipids were diphosphatidylglycerol,
      phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and
      phosphatidylinositolmannosides. Menaquinone MK-9(H4) was detected as the
      respiratory quinone; and anteiso-C17 : 0, iso-C16 : 0, iso-C15 : 0 and iso-C17 :
      0 as the predominant fatty acids. Pairwise comparison of the 16S rRNA gene
      sequences indicated that strain SYSU D8010T had a sequence similarity of 97.8 %
      to Saccharopolyspora halophila YIM 90500T. The genomic DNA G+C content of strain
      SYSU D8010T was determined to be 69.9 mol%. Based on the analyses of the
      phenotypic, genotypic and phylogenetic characteristics, strain SYSU D8010T was
      determined to represent a novel species of the genus Saccharopolyspora, for which
      the name Saccharopolyspora deserti sp. nov. is proposed. The type strain of the
      species is SYSU D8010T (=KCTC 39989T=CPCC 204620T).

PMID- 29458667
TI  - vacA s1m1 genotype and cagA EPIYA-ABC pattern are predominant among Helicobacter
      pylori strains isolated from Mexican patients with chronic gastritis.
AB  - PURPOSE: Virulent genotypes of Helicobacter pylori vacA s1m1/cagA+/babA2+ have
      been associated with severe gastric diseases. VacA, CagA and BabA are polymorphic
      proteins, and their association with the disease is allele-dependent. The aims of
      this work were: (i) to determine the prevalence of H. pylori by type of chronic
      gastritis; (ii) to describe the frequency of cagA, babA2 and vacA genotypes in
      strains from patients with different types of chronic gastritis; (iii) to
      characterize the variable region of cagA alleles. METHODOLOGY: A total of 164
      patients with chronic gastritis were studied. Altogether, 50 H. pylori strains
      were isolated, and the status of cagA, babA2 and vacA genotypes was examined by
      PCR. cagA EPIYA segment identification was performed using PCR and sequencing of
      cagA fragments of six randomly selected strains.Results/Key findings. The overall
      prevalence of H. pylori was 30.5 %. Eighty percent of the isolated strains were
      vacA s1m1, and the cagA and babA2 genes were detected in 74 and 32 % of the
      strains, respectively. The most frequent genotypes were vacA s1m1/cagA+/babA2-
      and vacA s1m1/cagA+/babA2+, with 40 % (20/50) and 28 % (14/50), respectively. In
      cagA+, the most frequent EPIYA motif was -ABC (78.4 %), and EPIYA-ABCC and -ABCCC
      motifs were found in 10.8 % of the strains. A modified EPIYT-B motif was found in
      66.6 % of the sequenced strains. CONCLUSION: H. pylori strains carrying vacA
      s1m1, cagA+ and babA2- genotypes were the most prevalent in patients with chronic
      gastritis from the south of Mexico. In the cagA+ strains, the EPIYA-ABC motif was
      the most common.

PMID- 29458668
TI  - Shift of microbial composition of peri-implantitis-associated oral biofilm as
      revealed by 16S rRNA gene cloning.
AB  - PURPOSE: Micro-organisms are important triggers of peri-implant inflammation and
      analysing their diversity is necessary for peri-implantitis treatment. This study
      aimed to analyse and compare the microbiota associated with individuals with peri
      implantitis, as well as clinically healthy implant sites. METHODOLOGY:
      Subgingival biofilm samples were taken from 10 individuals with peri-implantitis
      and from at least 1 clinically healthy implant. DNA was extracted and bacterial
      16S rRNA genes were amplified using universal primers. After cloning the PCR
      products, amplified inserts of positive clones were digested using restriction
      endonucleases, and the chosen clones were sequenced. The 16S rDNA-sequences were
      compared to those from the public sequence databases GenBank, EMBL and DDBJ to
      determine the corresponding taxa. RESULTS: Differing distributions of taxa
      belonging to the phyla Firmicutes, Bacteroidetes, Fusobacteria, Actinobacteria,
      Proteobacteria, Synergistetes, Spirochaetae and TM 7 were detected in both the
      healthy implant (HI) and the peri-implantitis (PI) groups. A significantly higher
      relative abundance of phylum Bacteroidetes, as well as of the species
      Fusobacterium nucleatum, were found in the PI group (P<0.05). The putative
      periodontal red complex (Porphyromonas gingivalis, Tannerella forsythia) was also
      detected at significantly higher levels in the PI group (P<0.05), whereas the
      yellow group, as well as the species Veillonella dispar, tended to be associated
      with the HI group. CONCLUSION: A shift in the healthy subgingival microbiota was
      shown in peri-implantitis-associated biofilm. Anaerobic Gram-negative
      periopathogens, including P. gingivalis and T. forsythia, seem to play an
      important role in peri-implantitis development and should be considered in
      treatment and prevention strategies.

PMID- 29458669
TI  - Chloromonas arctica sp. nov., a psychrotolerant alga from snow in the High Arctic
      (Chlamydomonadales, Chlorophyta).
AB  - With the advent of molecular phylogenetic methods, it has become possible to
      assess the bioversity of snow algae more accurately. In this study, we focused on
      a morphological, ultrastructural and taxonomic description of a new Chloromonas
      like alga isolated from snow in the High Arctic (Svalbard). Light and
      transmission electron microscopy revealed broad ellipsoidal or ellipsoidal
      cylindrical, occasionally spherical cells with a chloroplast without a pyrenoid,
      an inconspicuous eyespot and a papilla. The size difference and the
      aforementioned morphological traits clearly distinguished the alga from its
      closest counterparts within the genus Chloromonas. Moreover, we were able to
      cultivate the alga at both 5 and 20  degrees C, revealing the psychrotolerant
      nature of the strain. Phylogenetic analyses of the plastid rbcL and nuclear 18S
      rRNA gene showed that the alga is nested within a clade containing a number of
      psychrotolerant strains within the Chloromonadinia phylogroup (Chlorophyceae). In
      the rbcL phylogeny, the alga formed an independent lineage, sister to the
      freshwater species Chloromonas paraserbinowii. Comparisons of secondary structure
      models of a highly variable ITS2 rDNA marker showed support for a distinct
      species identity for the new strain. The ITS2 secondary structure of the new
      isolate differed from the closest matches 'Chlamydomonas' gerloffii and
      Choloromonas reticulata by three and five compensatory base changes,
      respectively. Considering the morphological and molecular differences from its
      closest relatives, a new psychrotolerant species from the Arctic, Choromonas
      arctica sp. nov., is proposed.

PMID- 29458670
TI  - Chicken anaemia virus evades host immune responses in transformed lymphocytes.
AB  - Chicken anaemia virus (CAV) is a lymphotropic virus that causes anaemia and
      immunosuppression in chickens. Previously, we proposed that CAV evades host
      antiviral responses in vivo by disrupting T-cell signalling, but the precise
      cellular targets and modes of action remain elusive. In this study, we examined
      gene expression in Marek's disease virus-transformed chicken T-cell line MSB-1
      after infection with CAV using both a custom 5K immune-focused microarray and
      quantitative real-time PCR at 24, 48 and 72 h post-infection. The data
      demonstrate an intricate equilibrium between CAV and the host gene expression,
      displaying subtle but significant modulation of transcripts involved in the T
      cell, inflammation and NF-kappaB signalling cascades. CAV efficiently blocked the
      induction of type-I interferons and interferon-stimulated genes at 72 h. The cell
      expression pattern implies that CAV subverts host antiviral responses and that
      the transformed environment of MSB-1 cells offers an opportunistic advantage for
      virus growth.

PMID- 29458671
TI  - Roseisolibacter agri gen. nov., sp. nov., a novel slow-growing member of the
      under-represented phylum Gemmatimonadetes.
AB  - A novel slow-growing bacterium, designated strain AW1220T, was isolated from
      agricultural floodplain soil sampled at Mashare (Kavango region, Namibia) by
      using a high-throughput cultivation approach. Strain AW1220T was characterized as
      a Gram-negative, non-motile, rod-shaped bacterium. Occasionally, some cells
      attained an unusual length of up to 35 um. The strain showed positive responses
      for catalase and cytochrome-c oxidase and divided by binary fission and/or
      budding. The strain had an aerobic chemoorganoheterotrophic metabolism and was
      also able to grow under micro-oxic conditions. Colonies were small and pink
      pigmented. Strain AW1220T was found to be a mesophilic, neutrophilic and non
      halophilic bacterium. Cells accumulated polyphosphate intracellularly and mainly
      utilized complex protein substrates for growth. 16S rRNA gene sequence
      comparisons revealed that strain AW1220T belonged to the class Gemmatimonadetes
      (=group 1). Its closest relatives were found to be Gemmatimonas aurantiaca T-27T
      (90.9 % gene sequence similarity), Gemmatimonas phototrophica AP64T (90.8 %) and
      Longimicrobiumterrae CB-286315T (84.2 %). The genomic G+C content was 73.3 mol%.
      The major fatty acids were iso-C15 : 0, C16 : 1omega7c and/or iso-C15 : 0 2-OH,
      iso-C17 : 1omega9c, iso-C15 : 0 3-OH and C16 : 0. The predominant respiratory
      quinone was MK-9, albeit minor amounts of MK-8 and MK-10 are also present. The
      polar lipids comprised major amounts of phosphatidylethanolamine,
      phosphatidylcholine, diphosphatidylglycerol and one unidentified
      phosphoglycolipid. On the basis of its polyphasic characterization, strain
      AW1220T represents a novel genus and species of the class Gemmatimonadetes for
      which the name Roseisolibacter agri gen. nov., sp. nov. is proposed, with the
      type strain AW1220T (=DSM 104292T=LMG 29977T).

PMID- 29458672
TI  - Optimization of triacylglycerol and starch production in Chlamydomonas debaryana
      NIES-2212 with regard to light intensity and CO2 concentration.
AB  - Triacylglycerol (TAG) and starch produced by micro-algae are potential sources of
      biofuel. Our previous studies showed that the unicellular green alga,
      Chlamydomonas debaryana NIES-2212, which is a rare species of Chlamydomonas that
      possesses phosphatidylcholine (PC), is a seed organism for the development of
      biofuel producers. This alga accumulates large amounts of TAG and starch under
      completely photo-autotrophic conditions during stationary phase without nutrient
      deprivation. The present study was performed to optimize the growth conditions of
      this alga with regard to light intensity and CO2 concentration to improve the
      efficiency of TAG and starch production. The growth rate of C. debaryana was
      greater at higher light intensity, although there was no significant difference
      in the final cell density of the culture. The highest contents of TAG and starch,
      approximately 200 fmol cell-1 and 600 pg cell-1, respectively, were achieved with
      a light intensity of 200 umol m-2 s-1 bubbled with air containing 5.0 % CO2.
      These results suggest that optimization of light intensity and CO2 concentration
      can enhance the productivity of TAG and starch by C. debaryana NIES-2212.

PMID- 29458673
TI  - Denture-associated biofilm infection in three-dimensional oral mucosal tissue
      models.
AB  - PURPOSE: In vitro analyses of virulence, pathogenicity and associated host cell
      responses are important components in the study of biofilm infections. The
      Candida-related infection, denture-associated oral candidosis, affects up to 60 %
      of denture wearers and manifests as inflammation of palatal tissues contacting
      the denture-fitting surface. Commercially available three-dimensional tissue
      models can be used to study infection, but their use is limited for many academic
      research institutions, primarily because of the substantial purchase costs. The
      aim of this study was to develop and evaluate the use of in vitro tissue models
      to assess infections by biofilms on acrylic surfaces through tissue damage and
      Candida albicans virulence gene expression. METHODOLOGY: In vitro models were
      compared against commercially available tissue equivalents (keratinocyte-only,
      SkinEthic; full-thickness, MatTek Corporation). An in vitro keratinocyte-only
      tissue was produced using a cancer-derived cell line, TR146, and a full-thickness
      model incorporating primary fibroblasts and immortalised normal oral
      keratinocytes was also generated. The in vitro full-thickness tissues
      incorporated keratinocytes and fibroblasts, and have potential for future further
      development and analysis. RESULTS: Following polymicrobial infection with
      biofilms on acrylic surfaces, both in-house developed models were shown to
      provide equivalent results to the SkinEthic and MatTek models in terms of tissue
      damage: a significant (P<0.05) increase in LDH activity for mixed species
      biofilms compared to uninfected control, and no significant difference (P>0.05)
      in the expression of most C. albicans virulence genes when comparing tissue
      models of the same type. CONCLUSION: Our results confirm the feasibility and
      suitability of using these alternative in vitro tissue models for such analyses.

PMID- 29458674
TI  - Restoration of sensitivity of a diverse set of drug-resistant Staphylococcus
      clinical strains by bactericidal protein P128.
AB  - PURPOSE: P128, a phage-derived lysin, exerts antibacterial activity on
      staphylococci by cleaving the pentaglycine-bridge of peptidoglycan. We sought to
      determine whether the presence of P128 could re-sensitize drug-resistant bacteria
      to antibiotics by virtue of its cell wall degrading property. METHODOLOGY: P128
      was tested in combination with standard-of-care (SoC) drugs by chequerboard
      assays on planktonic cells and biofilms of strains individually resistant to
      these drugs. The bactericidal effect of P128 and drug combinations on planktonic
      cells and biofilms was measured by c.f.u. reduction assays. A mouse model of MRSA
      bacteraemia was used to test the efficacy of P128 and oxacillin in combination.
      RESULTS: A combination of sub-MIC P128 (0.025-0.20 ug ml-1) and 0.5 ug ml-1 of
      oxacillin resulted in inhibition of bacterial growth in four MRSA strains.
      Similar results were seen with all the other drugs tested, wherein sub-MIC of
      P128 re-sensitized S. aureus and CoNS strains to SoC drugs. The chequerboard
      assays on strains of S. aureus and CoNS showed that combinations of P128 and
      antibiotics consistently inhibited bacterial growth on biofilms. Data from
      scanning electron microscopy and c.f.u. reduction assays on drug-resistant S.
      aureus and CoNS demonstrated that sub-MICs of P128 and SoC antibiotics could kill
      biofilm-embedded bacteria. In vivo, a combination of sub-therapeutic doses of
      P128 and oxacillin could help protect animals from fatal bacteraemia. CONCLUSION:
      The ability of P128 to re-sensitize bacteria to SoC drugs suggests that
      combinations of P128 and SoC antibiotics can potentially be developed to treat
      infections caused by drug-resistant strains of staphylococci.

PMID- 29458675
TI  - The contribution of SP100 to cottontail rabbit papillomavirus transcription and
      replication.
AB  - SP100 proteins are components of nuclear domain 10 structures and have been
      implicated as inhibitors of human papillomavirus (HPV) replication. In this
      study, we have addressed the role of SP100 in tumour formation by the cottontail
      rabbit (Sylvilagus floridanus) papillomavirus (CRPV or SfPV1) in a rabbit model.
      Tissue culture studies using rabbit keratinocyte lines indicated that rabbit
      SP100 is an interferon-beta-inducible gene similar to its human counterpart.
      Stable knockdown of SP100 by shRNA in a cell line harbouring CRPV genomes
      resulted in a decrease of viral early transcripts. In contrast, infection of
      domestic rabbits with recombinant CRPV genomes expressing short hairpin (sh)RNAs
      directed against SP100 did not reveal changes in tumour formation rate, tumour
      size or early viral transcript levels. However, late viral transcript levels and
      viral genome copies were consistently lower in CRPV/shSP100-induced tumours than
      in the control, but these differences did not reach statistical significance. In
      summary, this study suggests that rabbit SP100 is not an inhibitor but an
      activator of CRPV replication and transcription.

PMID- 29458676
TI  - Emergence of resistance to ciprofloxacin in Neisseria meningitidis in Brazil.
AB  - To prevent secondary invasive meningococcal disease (IMD) cases and outbreaks,
      antimicrobial prophylaxis of high-risk contacts is indicated. This study reports
      two ciprofloxacin-resistant Neisseria meningitidis strains in Brazil. The 3523 N.
      meningitidis isolates collected throughout Brazil from 2009 to 2016 were
      evaluated for antimicrobial resistance. Meningococcal isolates showing minimal
      inhibitory concentrations, MICs>=0.125ug ml-1 to ciprofloxacin, were analysed to
      determine the presence of mutations in the quinolone resistance-determining
      regions (QRDRs) of gyrA and parC genes. Two ciprofloxacin-resistant N.
      meningitidis isolates were found, both presenting a single mutation in the
      quinolone resistance-determining region of the gyrA gene. These results confirmed
      that ciprofloxacin is still a first-line drug for chemoprophylaxis. However, we
      highlight the importance of continued surveillance to monitor the trends of N.
      meningitidis susceptibility profiles to the antimicrobials recommended for
      chemoprophylaxis and IMD treatment.

PMID- 29458677
TI  - Methylomusa anaerophila gen. nov., sp. nov., an anaerobic methanol-utilizing
      bacterium isolated from a microbial fuel cell.
AB  - Abacterial strain, designated MMFC1T, was isolated from a methanol-fed microbial
      fuel cell that had been inoculated with sludge obtained from a wastewater
      treatmentfacility in a chemical plant. The strain grows by fermenting methanol to
      produce acetate under anaerobic conditions, while homoacetogenic growth is not
      observed. MMFC1T also grows on pyruvate and lactate but not on sugars and other
      organic acids. Cells are curved rods and motile, have peritrichous flagella, and
      form endospores. The genome sequence of strain MMFC1T supports the physiological
      data. Phylogenetic analysis based on the 16S rRNA gene sequence shows that strain
      MMFC1T is affiliated with the family Sporomusaceae, while the closest relative is
      Sporomusa ovata with nucleotide-sequencesimilarity of 93.5 %. Major fatty acids
      are iso-C13 : 0 3-OH, C16 : 1omega9 and iso-C17 : 0. On the basis of its
      physiological, genomic and phylogenetic features, a novel genus and species are
      proposed to accommodate strain MMFC1T, with the name Methylomusa anaerophila gen.
      nov., sp. nov. The type strain of Methylomusa anaerophila is MMFC1T (=JCM 31821T
      = KCTC 15592T).

PMID- 29458678
TI  - Accumulation of ornithine lipids in Vibrio cholerae under phosphate deprivation
      is dependent on VC0489 (OlsF) and PhoBR system.
AB  - Ornithine lipids (OLs) are phosphorus-free lipids found in many bacteria grown
      under phosphate deprivation, a condition that activates the PhoBR system and
      leads to phosphate uptake and metabolism. Two OL synthesis pathways have already
      been described. One depends on OlsB and OlsA acyltransferases to add,
      respectively, the first and second acyl chains to an ornithine molecule. The
      other pathway is carried out by OlsF, a bifunctional enzyme responsible for both
      acylation steps. Although Vibrio cholerae lacks olsBA genes, an olsF homologue
      (vc0489) was identified in its genome. In this work we demonstrated that V.
      cholerae produces OLs and expresses vc0489 in response to phosphate depletion, in
      a PhoBR-dependent manner. In Escherichia coli, under similar condition, vc0489
      expression leads to OL accumulation. These results indicate a strong connection
      between OL synthesis and VC0489 from V. cholerae and, for the first time, a
      direct regulation of an olsF homologue by the PhoBR system.

PMID- 29458679
TI  - Transitional and temporal changes in the mucosal and submucosal intestinal
      microbiota in advanced Crohn's disease of the terminal ileum.
AB  - PURPOSE: Crohn's disease is a chronic debilitating intestinal syndrome of unknown
      aetiology that is thought to result in part from an imbalance (dysbiosis) of the
      intestinal microbial populations, known as the microbiota. In this study we
      sought to compare the microbiota at the mucosal and submucosal levels at the
      resection margin in Crohn's disease to those in other intestinal dysbiotic
      disease controls to determine the level of bacterial translocation. METHODOLOGY:
      16S microbiota sequencing was performed on DNA extracted from mucosal and
      submucosal samples from resected intestinal tissues from Crohn's disease and
      controls. RESULTS: Grossly normal appearing tissue at the resection margin showed
      early signs, suggesting bacterial translocation, with two bacterial families
      having penetrated the mucosal surfaces. In contrast, 4 and 13 bacterial families
      were present within submucosal tissues at the disease centre and disease margin,
      respectively. Although there was no significant difference in biodiversity, there
      was increased bacterial richness in the Crohn's disease group as compared to non
      IBD controls. CONCLUSION: The presence and/or absence of certain bacteria
      suggested disease-specific ecological or micro-environmental pressures driving or
      excluding certain organisms in Crohn's disease. The data suggest that several of
      the dysbiotic conditions previously reported for Crohn's disease are not unique
      but common to general dysbiosis. The examination of multiple intestinal sites in
      advanced disease may provide a spectrum of disease from early onset at the
      resection margin to active disease at the disease margin and late-stage
      fibrostenotic disease at the centre of the lesion, and a unique etiopathogenic
      view of Crohn's disease.

PMID- 29458680
TI  - Colony analysis and deep learning uncover 5-hydroxyindole as an inhibitor of
      gliding motility and iridescence in Cellulophaga lytica.
AB  - Iridescence is an original type of colouration that is relatively widespread in
      nature but has been either incompletely described or entirely neglected in
      prokaryotes. Recently, we reported a brilliant 'pointillistic' iridescence in
      agar-grown colony biofilms of Cellulophaga lytica and some other marine
      Flavobacteria that exhibit gliding motility. Bacterial iridescence is created by
      a unique self-organization of sub-communities of cells, but the mechanisms
      underlying such living photonic crystals are unknown. In this study, we used
      Petri dish assays to screen a large panel of potential activators or inhibitors
      of C. lytica's iridescence. Derivatives potentially interfering with quorum
      sensing and other communication or biofilm formation processes were tested, as
      well as metabolic poisons or algal exoproducts. We identified an indole
      derivative, 5-hydroxyindole (5HI, 250 uM) which inhibited both gliding and
      iridescence at the colonial level. 5HI did not affect growth or cell respiration.
      At the microscopic level, phase-contrast imaging confirmed that 5HI inhibits the
      gliding motility of cells. Moreover, the lack of iridescence correlated with a
      perturbation of self-organization of the cell sub-communities in both the WT and
      a gliding-negative mutant. This effect was proved using recent advances in
      machine learning (deep neuronal networks). In addition to its effect on colony
      biofilms, 5HI was found to stimulate biofilm formation in microplates. Our data
      are compatible with possible roles of 5HI or marine analogues in the eco-biology
      of iridescent bacteria.

PMID- 29458681
TI  - Broad neutralization response in a subset of HIV-1 subtype C-infected viraemic
      non-progressors from southern India.
AB  - Broadly neutralizing antibodies (bnAbs) have been considered to be potent
      therapeutic tools and potential vaccine candidates to enable protection against
      various clades of human immunodeficiency virus (HIV). The generation of bnAbs has
      been associated with enhanced exposure to antigen, high viral load and low CD4+ T
      cell counts, among other factors. However, only limited data are available on the
      generation of bnAbs in viraemic non-progressors that demonstrate moderate to high
      viraemia. Further, since HIV-1 subtype C viruses account for more than 50 % of
      global HIV infections, the identification of bnAbs with novel specificities is
      crucial to enable the development of potent tools to aid in HIV therapy and
      prevention. In the present study, we analysed and compared the neutralization
      potential of responses in 70 plasma samples isolated from ART-naive HIV-1 subtype
      C-infected individuals with various disease progression profiles against a panel
      of 30 pseudoviruses. Among the seven samples that exhibited a neutralization
      breadth of >=70 %, four were identified as 'elite neutralizers', and three of
      these were from viraemic non-progressors while the fourth was from a typical
      progressor. Analysis of the neutralization specificities revealed that none of
      the four elite neutralizers were reactive to epitopes in the membrane proximal
      external region (MPER), CD4-binding site and V1V2 or V3 glycan. However, two of
      the four elite neutralizers exhibited enhanced sensitivity towards viruses
      lacking N332 glycan, indicating high neutralization potency. Overall, our
      findings indicate that the identification of potent neutralization responses with
      distinct epitope specificities is possible from the as yet unexplored Indian
      population, which has a high prevalence of HIV-1 subtype C infection.

PMID- 29458682
TI  - Frankia saprophytica sp. nov., an atypical, non-infective (Nod-) and non-nitrogen
      fixing (Fix-) actinobacterium isolated from Coriaria nepalensis root nodules.
AB  - Strain CN3T, a Coriaria nepalensis isolate, appears to form hyphae and sporangia
      typical of members fo the genus Frankia. However, it failed to form vesicles, to
      reduce acetylene and to induce nodules on its original host plant. A polyphasic
      approach was used here to determine the taxonomic status of strain CN3T. The 16S
      rRNA gene sequence of strain CN3T showed the highest sequence identity with
      Frankia asymbiotica type strain M16386T (99.4 %). Digital DNA-DNA hybridization
      between strains CN3T and M16386T was 25.7 %, which is clearly below the accepted
      cut-off point of 70 %. The G+C content of DNA was 71.8 mol%. Whole-cell
      hydrolysates of strain CN3T were rich in meso-diaminopimelic acid. Cell-wall
      sugars were composed of galactose, glucose, mannose, rhamnose and traces of
      ribose. The polar lipid profile contained phosphatidylinositol,
      phosphatidylglycerol, diphosphatidylglycerol, phosphoglycolipids, phospholipid,
      six uncharacterized glycolipids and two uncharacterized lipids. The predominant
      menaquinone (>25 %) was MK-9(H6). Major fatty acids (>15 %) of strain CN3T
      consisted of iso-C16 : 0, C17 : 1omega8c and C15 : 0. Based on 16S rRNA gene
      phylogeny, genome sequence analysis and phenotypic results, strain CN3T (=DSM
      105290T=CECT 9314T) is proposed to represent the type strain of a novel species,
      Frankia saprophytica sp. nov.

PMID- 29458683
TI  - Engineering Escherichia coli to grow constitutively on D-xylose using the carbon
      efficient Weimberg pathway.
AB  - Bio-production of fuels and chemicals from lignocellulosic C5 sugars usually
      requires the use of the pentose phosphate pathway (PPP) to produce pyruvate.
      Unfortunately, the oxidation of pyruvate to acetyl-coenzyme A results in the loss
      of 33 % of the carbon as CO2, to the detriment of sustainability and process
      economics. To improve atom efficiency, we engineered Escherichia coli to utilize
      d-xylose constitutively using the Weimberg pathway, to allow direct production of
      2-oxoglutarate without CO2 loss. After confirming enzyme expression in vitro, the
      pathway expression was optimized in vivo using a combinatorial approach, by
      screening a range of constitutive promoters whilst systematically varying the
      gene order. A PPP-deficient (DeltaxylAB), 2-oxoglutarate auxotroph (Deltaicd) was
      used as the host strain, so that growth on d-xylose depended on the expression of
      the Weimberg pathway, and variants expressing Caulobacter crescentus xylXAB could
      be selected on minimal agar plates. The strains were isolated and high-throughput
      measurement of the growth rates on d-xylose was used to identify the fastest
      growing variant. This strain contained the pL promoter, with C. crescentus xylA
      at the first position in the synthetic operon, and grew at 42 % of the rate on d
      xylose compared to wild-type E. coli using the PPP. Remarkably, the biomass yield
      was improved by 53.5 % compared with the wild-type upon restoration of icd
      activity. Therefore, the strain grows efficiently and constitutively on d-xylose,
      and offers great potential for use as a new host strain to engineer carbon
      efficient production of fuels and chemicals via the Weimberg pathway.

PMID- 29458684
TI  - Global survey of Klebsiella pneumoniae major porins from ertapenem non
      susceptible isolates lacking carbapenemases.
AB  - PURPOSE: To understand the diversity of porin disruption in Klebsiella
      pneumoniae, the major outer membrane protein (OMP) porins, OmpK35 and OmpK36,
      were examined in a set of isolates that did not harbour traditional carbapenem
      hydrolysing enzymes, but nevertheless tested non-susceptible to ertapenem.
      METHODS: A world-wide collection of Klebsiella pneumoniae isolates that were part
      of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance
      project over the years 2008-2014 were characterised with regard to their beta
      lactamase gene carriage and potential permeability defects. Four hundred and
      eighty-seven isolates that did not carry carbapenemase genes, but were non
      susceptible to ertapenem, were investigated by sequence analysis of the genes
      encoding OmpK35 and OmpK36. Isolates without obvious genetic lesions in either
      major porin gene were further examined by outer membrane protein SDS-PAGE.
      RESULTS: The majority of isolates, 83.0 % (404/487), exhibited clear genetic
      disruption in either or both of the ompK35 and ompK36 genes. Among the proportion
      of the collection with the highest ertapenem MIC value (>4 mg l-1), 60.5 %
      (115/190) showed mutation in both porin genes. Isolates without obvious genetic
      mutations were examined by SDS-PAGE, and 90.4 % (75/83) were found to lack or
      show altered expression of at least one of the major OMPs when compared to an
      ertapenem sensitive control strain. CONCLUSION: This study illustrates that porin
      deficiency in Klebsiella pneumoniae is a widespread phenomenon, and in
      combination with ESBLs and/or AmpC enzymes, likely accounts for the elevated
      ertapenem MICs observed in this study.

PMID- 29458685
TI  - Optimizing host cell physiology and stress avoidance for the production of
      recombinant human tumour necrosis factor alpha in Escherichia coli.
AB  - As high-level recombinant protein production (RPP) exerts a massive stress on the
      production host, an extensive literature on RPP optimization focuses on
      separating the growth phase from RPP production once sufficient biomass has been
      obtained. The aim of the current investigation was to optimize the benefits of
      the relatively neglected alternative strategy to achieve high-level RPP during
      growth by minimizing stress on the host. High yields of the biopharmaceutical
      recombinant human tumour necrosis factor alpha (rhTNFalpha) were obtained by fed
      batch fermentation relevant to industrial production based upon parameters that
      most severely affected RPP in preliminary laboratory scale batch cultures.
      Decreasing the inducer concentration and growth temperature, but increasing the
      production period, were far more effective for increasing RPP yields than
      changing the growth phase at which production was induced. High yields of up to 5
      g l-1 of rhTNFalpha were obtained with minimal plasmid loss, even in synthetic
      media that lack animal-derived components and are therefore fully compliant with
      regulatory requirements. Most of the product was soluble and biologically active.
      In summary, stress minimization was shown to be an effective way to optimize the
      production of rhTNFalpha. Data generated in shake-flask experiments allowed the
      design of intensified bioreactor cultures in which RPP and growth could be
      balanced, leading to higher yield of both rhTNFalpha and biomass than with
      previous fermentations. An additional benefit of this approach is avoidance of
      lysis during harvesting and downstream processing.

PMID- 29458687
TI  - MALDI-TOF mass spectrometry and high-consequence bacteria: safety and stability
      of biothreat bacterial sample testing in clinical diagnostic laboratories.
AB  - We considered the application of MALDI-TOF mass spectrometry for BSL-3 bacterial
      diagnostics, with a focus on the biosafety of live-culture direct-colony testing
      and the stability of stored extracts. Biosafety level 2 (BSL-2) bacterial species
      were used as surrogates for BSL-3 high-consequence pathogens in all live-culture
      MALDI-TOF experiments. Viable BSL-2 bacteria were isolated from MALDI-TOF mass
      spectrometry target plates after 'direct-colony' and 'on-plate' extraction
      testing, suggesting that the matrix chemicals alone cannot be considered
      sufficient to inactivate bacterial culture and spores in all samples. Sampling of
      the instrument interior after direct-colony analysis did not recover viable
      organisms, suggesting that any potential risks to the laboratory technician are
      associated with preparation of the MALDI-TOF target plate before or after
      testing. Secondly, a long-term stability study (3 years) of stored MALDI-TOF
      extracts showed that match scores can decrease below the threshold for reliable
      species identification (<1.7), which has implications for proficiency test panel
      item storage and distribution.

PMID- 29458686
TI  - DNA extraction from primary liquid blood cultures for bloodstream infection
      diagnosis using whole genome sequencing.
AB  - PURPOSE: Speed of bloodstream infection diagnosis is vital to reduce morbidity
      and mortality. Whole genome sequencing (WGS) performed directly from liquid blood
      culture could provide single-assay species and antibiotic susceptibility
      prediction; however, high inhibitor and human cell/DNA concentrations limit
      pathogen recovery. We develop a method for the preparation of bacterial DNA for
      WGS-based diagnostics direct from liquid blood culture. METHODOLOGY: We evaluate
      three commercial DNA extraction kits: BiOstic Bacteraemia, Amplex Hyplex and
      MolYsis Plus. Differential centrifugation, filtration, selective lysis and solid
      phase reversible immobilization bead clean-up are tested to improve human
      cells/DNA and inhibitor removal. Using WGS (Illumina/MinION), we assess human DNA
      removal, pathogen recovery, and predict species and antibiotic susceptibility
      inpositive blood cultures of 44 Gram-negative and 54 Staphylococcus
      species.Results/Key findings. BiOstic kit extractions yield the greatest mean DNA
      concentration, 94-301 ng ul-1, versus 0-2.5 ng ul-1 using Amplex and MolYsis
      kits. However, we note higher levels of inhibition (260/280 ratio 0.9-2.1) and
      human DNA (0.0-4.4*106 copies) in BiOstic extracts. Differential centrifugation
      (2000 g, 1 min) prior to BiOstic extraction reduces human DNA by 63-89 % with
      selective lysis minimizing by a further 62 %. Post-extraction bead clean-up
      lowers inhibition. Overall, 67 % of sequenced samples (Illumina MiSeq) contain
      <10 % human DNA, with >93 % concordance between WGS-based species and
      susceptibility predictions and clinical diagnosis. If >60 % of sequencing reads
      are human (7/98 samples) susceptibility prediction becomes compromised. Novel
      MinION-based WGS (n=9) currently gives rapid species identification but not
      susceptibility prediction. CONCLUSION: Our method for DNA preparation allows WGS
      based diagnosis direct from blood culture bottles, providing species and
      antibiotic susceptibility prediction in a single assay.

PMID- 29458688
TI  - Implementation of a rapid influenza A/B and RSV direct molecular assay improves
      emergency department oseltamivir use in paediatric patients.
AB  - PURPOSE: Influenza A virus (FluA), influenza B virus (FluB) and respiratory
      syncytial virus (RSV) illnesses increase hospitalizations during seasonal
      epidemics. METHODOLOGY: To determine the utility of the Simplexa FluA/B & RSV
      Direct Assay (Direct Flu/RSV) and its impact on oseltamivir use, we offered this
      assay to emergency department (ED) patients with influenza-like illness. RESULTS:
      Utilization of the Direct Flu/RSV provided a turnaround time (TAT) of 2 hours.
      Compared to the flu season prior to implementation of the Direct Flu/RSV,
      clinicians were more likely to prescribe 5 days of oseltamivir therapy for Direct
      Flu/RSV-positive patients in comparison to those with a negative test.
      CONCLUSIONS: Use of Direct Flu/RSV provides results rapidly, which leads to more
      appropriate use of oseltamivir. The ease of use of this assay and quick TAT
      allows for prompt decision-making, which is essential for patient care and
      effective disease control during the influenza season.

PMID- 29458689
TI  - The YscE/YscG chaperone and YscF N-terminal sequences target YscF to the Yersinia
      pestis type III secretion apparatus.
AB  - The needle structures of type III secretion (T3S) systems are formed by the
      secretion and polymerization of a needle subunit protein, YscF in Yersinia
      pestis. A subset of T3S systems employ unique heterodimeric chaperones, YscE and
      YscG in Y. pestis, to prevent the polymerization of needle subunits within the
      bacterial cell. We demonstrate that the YscE/YscG chaperone is also required for
      stable YscF expression and for secretion of YscF. Overexpression of a functional
      maltose-binding protein (MBP)-YscG hybrid protein stabilized cytoplasmic YscF but
      YscF was not secreted in the absence of YscE. Furthermore, a YscE mutant protein
      was identified that functioned with YscG to stabilize cytosolic YscF; however,
      YscF was not secreted. These findings confirm a role for the YscE/YscG chaperone
      in YscF secretion and suggest that YscE may have a specific role in this process.
      Recent studies have shown that YscF deleted of its N-terminal 15 residues is
      still secreted and functional, suggesting that YscF may not require an N-terminal
      secretion signal. However, we demonstrate that YscF contains an N-terminal
      secretion signal and that a functional N-terminal signal is required for YscF
      secretion.

PMID- 29458690
TI  - Anti-inflammatory effect of two Lactobacillus strains during infection with
      Gardnerella vaginalis and Candida albicans in a HeLa cell culture model.
AB  - Lactobacilli are the dominant bacteria of the vaginal tract of healthy women and
      they play a major role in the maintenance of mucosal homeostasis, preventing
      genital infections, such as bacterial vaginosis (BV) and vulvovaginal candidiasis
      (VVC). It is now known that one mechanism of this protection is the influence
      that lactobacilli can exert on host immune responses. In this context, we
      evaluated two Lactobacillus strains (L. plantarum 59 and L. fermentum 137) for
      their immunomodulatory properties in response to Gardnerella vaginalis (BV) or
      Candida albicans (VVC) infections in a HeLa cell infection model. G. vaginalis
      and C. albicans triggered the secretion of pro-inflammatory cytokines (TNF-alpha,
      IL-1beta, IL-6 and IL-8) and the activation of NF-kappaB in HeLa cells, in
      contrast to L. plantarum 59 and L. fermentum 137. Treatments with the
      Lactobacillus strains or their cell-free supernatants before (pre-treatment) or
      after (post-treatment) the challenge with the pathogens resulted in decreased
      secretion of pro-inflammatory cytokines and decreased activation of NF-kappaB.
      The treatments with Lactobacillus strains not only decreased the secretion of IL
      8, but also its expression, as confirmed by gene reporter luciferase assay,
      suggesting transcription-level control by lactobacilli. In conclusion, L.
      plantarum 59 and L. fermentum 137 were confirmed to have an anti-inflammatory
      effect against G. vaginalis and C. albicans and they were able to influence
      signalling in NF-kappaB pathway, making them interesting candidates as probiotics
      for the prevention or treatment of BV and VVC.

PMID- 29458691
TI  - Nightmare Themes: An Online Study of Most Recent Nightmares and Childhood
      Nightmares.
AB  - STUDY OBJECTIVES: Even though the common diagnostic criteria (ICSD-3, DSM-5)
      acknowledge that nightmares do not only contain anxiety/fear (definition of the
      ICD-10) but also other emotions such as grief, disgust, and anger, the definition
      of a nightmare still focuses on threats to survival, security, or physical
      integrity. However, empirical studies on nightmare content in larger samples are
      scarce. METHODS: The current study elicited 1,216 of the most recent nightmares
      including childhood nightmares of a population-based sample. RESULTS: The
      findings show that nightmares encompass a diversity of different topics, being
      chased, physical aggression, including death/injury of close persons. Infrequent
      themes like being the aggressor and suicide are of special interest as they might
      be related to waking-life psychopathology. CONCLUSIONS: The variety of nightmare
      topics clearly indicate that current definitions of nightmare content are too
      narrow. Future studies should look into nightmare content of persons in whom
      nightmare disorder has been diagnosed.

PMID- 29458692
TI  - Effect of Sleep-Disordered Breathing on Albuminuria in 273 Patients With Type 2
      Diabetes.
AB  - STUDY OBJECTIVES: Sleep-disordered breathing (SDB) can induce hyperglycemia,
      hypertension, and oxidative stress, conditions that are known to cause kidney
      damage. Therefore, SDB may exacerbate albuminuria, which is an established marker
      of early-stage kidney damage in patients with type 2 diabetes mellitus (T2DM).
      The association between SDB and albuminuria in patients with T2DM was
      investigated in this study. METHODS: This cross-sectional study included 273
      patients with T2DM who underwent portable sleep testing and measurement of urine
      albumin to creatinine ratio (UACR). The association between the severity of SDB
      and albuminuria was investigated. Patients were divided into three groups
      according to the respiratory event index (REI): the no or mild group (REI < 15
      events/h), moderate (REI 15 to < 30 events/h), and severe (REI >= 30 events/h).
      Albuminuria was defined as UACR >= 3.4 mg/mmol creatinine. Logistic regression
      analysis for albuminuria included the categorical REI as the independent
      variable. RESULTS: The median (interquartile range) REI of all patients (age 57.9
      +/- 11.9 years, mean +/- standard deviation, male sex 81.7%, body mass index 26.7
      [24.2-29.5] kg/m2, estimated glomerular filtration rate 82 [65-97] mL/min/1.73
      m2) was 13.0 (7.0-24.2) events/h. The REI, as a categorical variable, was
      significantly associated with albuminuria after adjustment for other risk factors
      for albuminuria; REI 15 to < 30 events/h: odds ratio (OR) 3.35, 95% confidence
      interval (95% CI), 1.68-6.67, P < .001; REI >= 30: OR 8.52, 95% CI, 3.52-20.63, P
      < .001). In addition, the natural logarithm-transformed REI of all patients also
      correlated significantly with albuminuria. CONCLUSIONS: The severity of SDB is
      associated with albuminuria in patients with T2DM.

PMID- 29458693
TI  - The Impact of Continuous Positive Airway Pressure on Circulating IGF-1 in
      Patients With Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a disease with metabolic and
      cardiovascular consequences and is associated with decreased serum concentrations
      of insulin-like growth factor-1 (IGF-1). The aim of this study was to investigate
      whether continuous positive airway pressure (CPAP) will increase serum IGF-1
      concentration in patients with OSA. METHODS: Patients with moderate to severe OSA
      were recruited from a sleep clinic and serum IGF-1 was measured before initiation
      of CPAP and at follow-up after 4.8 +/- 2.5 months. Patients adherent to CPAP
      treatment (usage >= 4 h/night) were compared with those considered to be
      nonadherent (usage < 4 h/night). RESULTS: Complete data were obtained from 69
      patients (86% male, age 56 +/- 12 years, respiratory event index 43 +/- 21
      events/h, Epworth Sleepiness Scale score 12 +/- 5). In those adherent to CPAP (n
      = 42), there was an increase in serum IGF-1 concentration with 21.1 (95%
      confidence interval [CI]: 13.1 to 29.2) MUg/L compared to 4.7 (95% CI: -4.1 to
      13.5) MUg/L in the nonadherent group (n = 27) (P = .0083). In a linear
      multivariate model adjusting for sex, age, body mass index, respiratory event
      index, and mean oxygen saturation during the night recording, the change in serum
      IGF-1 concentration was significantly associated with adherence to CPAP treatment
      (adjusted beta coefficient: 21.8, 95% CI: 10.2 to 33.4) and inversely associated
      with change in body mass index (adjusted beta coefficient: -7.1, 95% CI: -11.3 to
      -3.0) and change in hemoglobin A1c (adjusted beta coefficient: -1.8, 95% CI: -33
      to -0.3). CONCLUSIONS: CPAP usage >= 4 h/night is associated with increased serum
      IGF-1 concentration in male patients with OSA.

PMID- 29458694
TI  - Persistent High Residual AHI After CPAP Use.
AB  - ABSTRACT: Treatment-emergent central sleep apnea has recently been noted after
      various treatment modalities for obstructive sleep apnea. It often remits
      spontaneously or can be treated with continuous positive airway pressure.
      However, we encountered a pediatric patient with obstructive sleep apnea who
      presented with severe complications, including growth failure, attention-deficit
      hyperactivity disorder, poor school performance, daytime sleepiness, and urinary
      difficulty that required permanent cystostomy. His obstructive sleep apnea
      resolved after adenotonsillectomy. However, treatment-emergent central sleep
      apnea developed after adenotonsillectomy and was further aggravated after
      continuous positive airway pressure and bilevel positive airway pressure without
      a backup respiratory rate use. After bilevel positive airway pressure with a
      backup respiratory rate treatment for 3 months initially, all his symptoms
      improved, except growth failure. Later, after adaptive servoventilation was used
      for 10 months, the patient's growth began to improve.

PMID- 29458695
TI  - Comorbid Insomnia With Obstructive Sleep Apnea: Clinical Characteristics and Risk
      Factors.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and chronic insomnia are two
      common sleep disorders and both are considered independent risk factors for heart
      disease. The aim of this study was to investigate the prevalence of comorbid
      insomnia with OSA and to compare its clinical characteristics with those of OSA
      without insomnia. METHODS: Patients who visited two tertiary university hospital
      sleep centers were screened. Those with a diagnosis of OSA using polysomnography
      were divided into two groups based on their scores on the Korean version of the
      Insomnia Severity Index (ISI-K): OSA with insomnia (OSA+I) (ISI-K score >= 15)
      and OSA without insomnia (OSA-I) (ISI-K score < 15). Subjective symptoms were
      evaluated using sleep questionnaires including ISI-K. Demographic and clinical
      characteristics of OSA+I and OSA-I were compared. RESULTS: Out of 476 patients
      with OSA, 139 (29.2%) had significant insomnia. Patients in the OSA+I group had a
      higher percentage of females (35.3% versus 19.6%, P < .001) and have higher rates
      of heart disease (19.4% versus 8.6%, P < .001). OSA+I group showed lower quality
      of life, lower quality of sleep, higher sleep propensity, and higher depression
      as measured by the Korean versions of the Short-Form 36-Item Health Survey,
      Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Beck Depression
      Inventory, respectively. There were no significant differences in adherence to
      continuous positive airway pressure between the groups. CONCLUSIONS: There is a
      high prevalence of comorbid insomnia with OSA (29.2%), consistent with previous
      findings in Western studies. Comorbid insomnia with OSA may constitute a
      cumulative risk factor for cardiovascular disease. These findings warrant further
      investigation into the mechanisms involved in its pathogenesis and devising more
      efficient treatments.

PMID- 29458696
TI  - Characterization of Respiratory Events in Obstructive Sleep Apnea Using
      Suprasternal Pressure Monitoring.
AB  - STUDY OBJECTIVES: In obstructive sleep apnea (OSA) esophageal pressure (Pes) is
      the gold standard for measurement of respiratory effort, and respiratory
      inductance plethysmography (RIP) is considered an accepted measurement technique.
      However, the use of RIP could lead to limited accuracy in certain cases and
      therefore suprasternal pressure (SSP) monitoring might improve the reliability of
      OSA diagnosis. We aimed to use SSP for the visual characterization of respiratory
      events in adults and compared results to those obtained by RIP from
      polysomnography (PSG). METHODS: In patients with OSA, a 1-night SSP recording
      using the PneaVoX sensor (Cidelec, Sainte-Gemmes-sur-Loire, France) was done. In
      parallel, PSG was performed according to American Academy of Sleep Medicine
      criteria. A subgroup of patients agreed to have Pes measurement in addition.
      Characterizations of apneas as obstructive, central, and mixed as well as
      hypopneas as central and obstructive were done by visual evaluation of SSP, RIP,
      and Pes in random order by two independent scores (S1 and S2). The sensitivity
      and specificity of characterization by SSP compared to RIP and to Pes were
      calculated. RESULTS: Synchronous recordings of SSP and PSG were analyzed from n =
      34 patients with OSA (AHI 34.1 +/- 24.2 events/h); 9 of them had synchronized Pes
      monitoring as well. Interscorer agreement for apnea characterization as
      obstructive, central, and mixed based on SSP, RIP, and Pes were found, with R2
      values from 0.91-0.99. The sensitivity of SSP in apnea characterization with
      reference to RIP (S1/S2) was 91.5%/92.3% for obstructive, 82.7%/76.2% for
      central, and 87.4%/79.9% for mixed. The sensitivity of SSP in apnea
      characterization with reference to Pes was (S1/S2) 93.1%/92.1% for obstructive,
      80.8%/81.6% for central, and 91.7%/90.8% for mixed. Hypopnea was only classified
      for the nine patients with Pes. CONCLUSIONS: This study demonstrated a good
      agreement in the detection of respiratory effort with the SSP signal using the
      PneaVoX sensor compared to the RIP belts signals as well as to the Pes signal.
      These findings were consistently found by two independent scorers. In summary,
      results suggest that SSP is a reliable signal for the classification of
      respiratory events and could be used as an additional tool for OSA
      characterization in clinical practice.

PMID- 29458697
TI  - Long-Term Impact of Sleep-Disordered Breathing on Quality of Life in Children
      With Obesity.
AB  - STUDY OBJECTIVES: (1) To determine baseline quality of life (QOL) among children
      with obesity and newly diagnosed moderate-severe sleep-disordered breathing (SDB)
      and to compare it to the reported QOL of children with obesity or SDB alone and
      healthy children. (2) To evaluate QOL change after 1 year. METHODS: A prospective
      multicenter cohort study was conducted in children (8-16 years) with obesity,
      prescribed positive airway pressure (PAP) therapy for moderate-severe SDB.
      Outcomes included parent-proxy and self-report total and subscale scores on the
      PedsQL questionnaire (baseline and 1-year). RESULTS: Total PedsQL scores were
      indicative of impaired QOL in 69% of cases based on parent-report and in 62% on
      self-report. Parents reported significantly lower QOL in our cohort than that
      reported in other studies for children with obesity or SDB alone or healthy
      children, on total PedsQL score and on social and psychosocial subscales. PedsQL
      total scores for participants were significantly higher (mean difference 7.3 +/-
      15.3, P = .03) than those reported by parents. Parents reported significant
      improvements in total PedsQL (mean change 7.29 +/- 13.73, P = .04) and social
      functioning (mean change 17.65 +/- 24.69, P = .04) scores after 1 year. No
      significant differences were found by children's self-report or by PAP adherence.
      CONCLUSIONS: QOL of children with obesity and SDB is lower than in children with
      obesity or SDB alone or healthy children. One year later, children reported no
      significant changes in QOL; parents reported significant improvements in total
      PedsQL and social functioning scores. PAP adherence did not significantly affect
      QOL change in this population. COMMENTARY: A commentary on this article appears
      in this issue on page 307.

PMID- 29458698
TI  - Non-24-Hour Sleep-Wake Circadian Rhythm Disorder in a Sighted Male With Normal
      Functioning.
AB  - ABSTRACT: This is a rare case of non-24-hour sleep-wake rhythm disorder in a
      sighted male with normal functioning. The patient, a 23-year-old doctorate
      graduate student, presented with difficulty falling asleep and excessive daytime
      sleepiness. He reported variable sleep and wake times. Overnight baseline
      polysomnography was unremarkable and his Multiple Sleep Latency Test was
      significant for short mean sleep latency. Sleep diary and actigraphy were
      obtained, which demonstrated a pattern of delaying of sleep and wake times each
      day. He had excellent symptom response to nightly melatonin.

PMID- 29458699
TI  - Continuous Positive Airway Pressure Therapy in Gestational Diabetes With
      Obstructive Sleep Apnea: A Randomized Controlled Trial.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with gestational
      diabetes mellitus (GDM). This study assessed the effects of continuous positive
      airway pressure (CPAP) in obese pregnant females with GDM and OSA. METHODS: A
      randomized controlled trial was conducted (April 2014 - June 2016). Obese females
      at 24 to 34 weeks gestation and with diet-controlled GDM were screened for OSA.
      Those with OSA were randomly assigned to receive 2 weeks nightly CPAP or be part
      of a waitlist control group. After 2 weeks, all patients were offered CPAP. The
      primary outcome was glucose metabolism, obtained from an oral meal tolerance test
      (MTT) at baseline and 2 weeks. Pregnancy outcomes were collected. RESULTS:
      Eighteen patients were randomized to CPAP and 18 to control groups. There were no
      significant changes between groups in fasting glucose, glucose response to MTT,
      and insulin sensitivity or secretion after 2 weeks. Those adherent to CPAP had
      significantly improved insulin secretion (P = .016) compared to the control
      group. When a counterfactual instrumental variable approach was applied to deal
      with nonadherence, the CPAP group had significantly improved insulin secretion (P
      = .002) and insulin sensitivity (P = .015). Lower rates of preterm delivery (P =
      .002), unplanned cesarean section (P = .005), and neonatal intensive care unit
      admissions (P < .001) were observed among those who used CPAP longer than 2
      weeks. CONCLUSIONS: Two weeks of CPAP in females with GDM and OSA did not result
      in improved glucose levels, but insulin secretion improved in those adherent to
      CPAP. Continued CPAP use was possibly associated with improved pregnancy
      outcomes. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title:
      Obstructive Sleep Apnea and Gestational Diabetes: Incidence and Effects of
      Continuous Positive Airway Pressure Treatment on Glucose Metabolism; Identifier:
      NCT02108197; URL: https://clinicaltrials.gov/ct2/show/NCT02108197.

PMID- 29458700
TI  - Sleep Health and Predicted Cardiometabolic Risk Scores in Employed Adults From
      Two Industries.
AB  - STUDY OBJECTIVES: Sleep disorders and sleep deficiency can increase the risk for
      cardiovascular disease. Less is known about whether multiple positive attributes
      of sleep health known as the SATED (satisfaction, alertness, timing, efficiency,
      and duration) model, can decrease future cardiovascular disease risks. We
      examined whether and how a variety of indicators of sleep health predicted 10
      year estimated cardiometabolic risk scores (CRS) among employed adults. METHODS:
      Workers in two industries-extended care (n = 1,275) and information technology
      (IT; n = 577)-reported on habitual sleep apnea symptoms and sleep sufficiency,
      and provided 1 week of actigraphy data including nighttime sleep duration, wake
      after sleep onset (WASO), sleep timing, and daytime napping. Workers also
      provided biomarkers to calculate future cardiometabolic risk. RESULTS: More sleep
      apnea symptoms predicted higher CRS in both industries. More sleep sufficiency,
      less WASO, and less daytime napping (having no naps, fewer naps, and shorter nap
      duration) were also linked to lower CRS, but only in the extended care workers.
      There was no effect of sleep duration in both industries. In the IT employee
      sample, shorter sleep duration (<= 6 hours versus 6-8 hours) and more naps
      strengthened the link between sleep apnea and CRS. CONCLUSIONS: Sleep health,
      measured by both subjective and objective methods, was associated with lower
      cardiometabolic disease risks among extended care workers (lower to middle wage
      workers). Sleep apnea was an important predictor of CRS; for the IT workers, the
      link between sleep apnea and CRS was exacerbated when they had poorer sleep
      health behaviors.

PMID- 29458701
TI  - Impact of Arterial Stiffness on WatchPAT Variables in Patients With Obstructive
      Sleep Apnea.
AB  - STUDY OBJECTIVES: The WatchPAT is a wrist-worn portable device that creates
      integration data regarding peripheral arterial tone (PAT), oxyhemoglobin
      saturation, heart rate, and actigraphy to diagnose or screen for obstructive
      sleep apnea (OSA). Previous studies have demonstrated the efficacy and validity
      of respiratory variables measured by the WatchPAT compared to those using
      polysomnography (PSG). However, the effects of arterial stiffness or
      atherosclerosis on WatchPAT parameters remain to be elucidated. METHODS: Sixty
      one consecutive patients with suspected OSA who underwent home-based testing with
      the WatchPAT 200, standard in-laboratory overnight polysomnography (PSG), and
      pulse wave velocity (PWV) as an index of arterial stiffness were studied. All PSG
      recordings were scored manually using the American Academy of Sleep Medicine
      criteria, whereas WatchPAT data were analyzed by an automatic algorithm. We
      evaluated how arterial stiffness affected respiratory event index data in
      WatchPAT (WP-AHI), because WP-AHI could be partly influenced by PAT, comparing WP
      AHI and the apneahypopnea index measured by PSG (PSG-AHI) in consideration of PWV
      result. RESULTS: Overall, WP-AHI was moderately correlated to PSG-AHI, but WP-AHI
      was significantly lower than PSG-AHI (28.4 +/- 19.2 versus 53.6 +/- 30.2
      events/h, P < .0001). For the lower PWV group, there was a significant
      correlation and good agreement between the WP-AHI and PSG-AHI, but as the PWV
      increased, there was low correlation between the WP-AHI and PSG-AHI. CONCLUSIONS:
      Arterial stiffness may affect the respiratory variables measured by WatchPAT in
      patients with OSA. COMMENTARY: A commentary on this article appears in this issue
      on page 301.

PMID- 29458703
TI  - A Case of Narcolepsy Type 2 and Postural Tachycardia Syndrome Secondary to
      Lesions of the Thalamus and Amygdala.
AB  - ABSTRACT: Although there are reports of narcolepsy type 1 caused by lesions of
      the central nervous system, there are far fewer reports of narcolepsy type 2
      (NT2) caused by discrete brain lesions. We report a case of a patient in whom NT2
      was diagnosed after a viral illness, and inflammatory lesions in the right
      thalamus and amygdala were found. In addition, symptoms of autonomic impairment
      developed and postural tachycardia syndrome was subsequently diagnosed in this
      patient. To our knowledge this is the first reported case of NT2 resulting from
      central nervous system lesions in these discrete locations, as well as the first
      reported case of postural tachycardia syndrome associated with narcolepsy.

PMID- 29458702
TI  - The Association Between Insomnia and Sleep Duration in Adults With Attention
      Deficit Hyperactivity Disorder: Results From a General Population Study.
AB  - STUDY OBJECTIVES: Insomnia and short or long sleep duration are important
      comorbid conditions in adults with attention-deficit hyperactivity disorder
      (ADHD), but reports of the association vary. In a general population study, we
      evaluated the relationship between ADHD symptom severity, insomnia symptoms, and
      sleep duration in adults. METHODS: Data were from the third wave of the
      Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2; n = 4,618).
      ADHD symptom severity and symptom dimensions (hyperactivity and inattention) were
      assessed using the Adult ADHD Self-Report Scale screener. Self-reported insomnia
      symptoms (Insomnia Rating Scale; IRS) were defined as clinically relevant if IRS
      >= 9. Self-reported short sleep duration was defined as <= 6 hours, and long
      sleep duration as >= 10 hours. RESULTS: Within the group with clinically relevant
      ADHD symptoms, 43% reported significant insomnia symptoms (odds ratio [OR] =
      2.66, 95% confidence interval [CI] 1.74-4.07); 41% short sleep duration (relative
      risk ratio [RRR] = 1.94, 95% CI 1.31-2.85) and 6% long sleep (RRR = 5.87, 95% CI
      1.97-17.45). Increased inattention symptoms were associated with IRS >= 9, short
      and long sleep duration in fully adjusted models (OR = 1.10, 95% CI 1.06-1.14;
      RRR = 1.06, 95% CI 1.02-1.09; RRR = 1.16, 95% CI 1.05-1.28, respectively).
      Increased hyperactivity symptoms were associated with IRS >= 9 (OR = 1.17, 95% CI
      1.11-1.23) and short sleep duration (RRR = 1.12, 95% CI 1.05-1.19). CONCLUSIONS:
      Both clinically significant ADHD symptoms and inattention and hyperactivity
      symptom dimensions were consistently associated with insomnia symptoms and
      altered sleep duration. These associations confirm that sleep disturbances should
      be assessed and given appropriate clinical attention in adults with ADHD.

PMID- 29458704
TI  - Evaluation of Cardiovascular Risk Factors and Restless Legs Syndrome in Women and
      Men: A Preliminary Population-Based Study in China.
AB  - STUDY OBJECTIVES: Many studies have investigated the association between restless
      legs syndrome (RLS) and cardiovascular risk factors, leading to conflicting
      results. Therefore, the aim of the current study was to determine whether RLS is
      associated with cardiovascular risk factors and disease. METHODS: This cross
      sectional study included 5,324 consecutive subjects who visited the Physical
      Examination Center of The First Affiliated Hospital of Zhengzhou University for
      their yearly routine physical examination. Participants underwent a face-to-face
      interview with a neurologist for the assessment of RLS, based on the
      International Restless Legs Study Group criteria. They also completed a
      questionnaire related to cardiovascular risk factors and other health-related and
      demographic information. Logistic regression was used to assess which of the
      demographic and cardiovascular risk factors increased the odds of RLS. Then,
      unadjusted and adjusted models were designed to determine whether RLS was
      associated with increased odds of cardiovascular disease, coronary artery
      disease, or hypertension. RESULTS: RLS was observed in 9.2% of the participants.
      Multivariable logistic regression models, which included the covariates age, sex,
      body mass index, smoking status, hypercholesterolemia, and Pittsburgh Sleep
      Quality Index score (dichotomized at 5), demonstrated that female sex (odds ratio
      [OR]: 2.42, 95% confidence interval [CI]: 1.99-2.95), smoking (OR: 1.96, 95% CI:
      1.31-2.92), high cholesterol (OR: 1.30, 95% CI: 1.03-1.64), and PSQI score > 5
      (OR: 5.61, 95% CI: 2.14-14.69) are significantly associated with RLS.
      Additionally, RLS was associated with hypertension, after adjusting for age, sex,
      body mass index, smoking, hypercholesterolemia, Pittsburgh Sleep Quality Index
      score > 5, diabetes, anemia, and decreased renal function. CONCLUSIONS: RLS is
      associated with the prevalence of hypertension but not with that of
      cardiovascular disease or coronary artery disease.

PMID- 29458705
TI  - Reliability of the Structured Clinical Interview for DSM-5 Sleep Disorders
      Module.
AB  - STUDY OBJECTIVES: To develop and demonstrate interrater reliability for a
      Structured Clinical Interview for Diagnostic and Statistical Manual of Mental
      Disorders, Fifth Edition (DSM-5) Sleep Disorders (SCISD). METHODS: The SCISD was
      designed to be a brief, reliable, and valid interview assessment of adult sleep
      disorders as defined by the DSM-5. A sample of 106 postdeployment active-duty
      military members seeking cognitive behavioral therapy for insomnia in a
      randomized clinical trial were assessed with the SCISD prior to treatment to
      determine eligibility. Audio recordings of these interviews were double-scored
      for interrater reliability. RESULTS: The interview is 8 pages long, includes 20
      to 51 questions, and takes 10 to 20 minutes to administer. Of the nine major
      disorders included in the SCISD, six had prevalence rates high enough (ie, n >=
      5) to include in analyses. Cohen kappa coefficient (kappa) was used to assess
      interrater reliability for insomnia, hypersomnolence, obstructive sleep apnea
      hypopnea (OSAH), circadian rhythm sleep-wake, nightmare, and restless legs
      syndrome disorders. There was excellent interrater reliability for insomnia (1.0)
      and restless legs syndrome (0.83); very good reliability for nightmare disorder
      (0.78) and OSAH (0.73); and good reliability for hypersomnolence (0.50) and
      circadian rhythm sleep-wake disorders (0.50). CONCLUSIONS: The SCISD is a brief,
      structured clinical interview that is easy for clinicians to learn and use. The
      SCISD showed moderate to excellent interrater reliability for six of the major
      sleep disorders in the DSM-5 among active duty military seeking cognitive
      behavioral therapy for insomnia in a randomized clinical trial. Replication and
      extension studies are needed. CLINICAL TRIAL REGISTRATION: Registry:
      ClinicalTrials.gov; Title: Comparing Internet and In-Person Brief Cognitive
      Behavioral Therapy of Insomnia; Identifier: NCT01549899; URL:
      https://clinicaltrials.gov/ct2/show/NCT01549899.

PMID- 29458706
TI  - Objective Sleep and Personality.

PMID- 29458707
TI  - Using Nasopharyngeal Stenting Devices as a Novel Way of Surgical Planning for
      Obstructive Sleep Apnea.

PMID- 29458708
TI  - Watch What You're Doing!

PMID- 29458709
TI  - Quality of Life With PAP Therapy for Obese Children.

PMID- 29458710
TI  - Doomed to Repeat History: The Burden of Trauma-Related Nightmares in Military
      Personnel.

PMID- 29458711
TI  - Life in the fast lane.
AB  - Dormice born late in the year start to prepare for winter sooner than mice born
      earlier in the year.

PMID- 29458712
TI  - Implications of being born late in the active season for growth, fattening,
      torpor use, winter survival and fecundity.
AB  - For hibernators, being born late in the active season may have important effects
      on growth and fattening, hence on winter survival and reproduction. This study
      investigated differences in growth, fattening, energetic responses, winter
      survival and fecundity between early-born ('EB') and late-born ('LB') juvenile
      garden dormice (Eliomys quercinus). LB juveniles grew and gained mass twice as
      fast as EB individuals. Torpor use was low during intensive growth, that are,
      first weeks of body mass gain, but increased during pre-hibernation fattening. LB
      juveniles showed higher torpor use, reached similar body sizes but lower fat
      content than EB individuals before hibernation. Finally, LB individuals showed
      similar patterns of hibernation, but higher proportion of breeders during the
      following year than EB dormice. These results suggest that torpor is incompatible
      with growth but promotes fattening and consolidates pre-hibernation fat depots.
      In garden dormice, being born late in the reproductive season is associated with
      a fast life history.

PMID- 29458713
TI  - Ectomycorrhizal fungi increase the vitality of Norway spruce seedlings under the
      pressure of Heterobasidion root rot in vitro but may increase susceptibility to
      foliar necrotrophs.
AB  - We tested if root colonisation by ectomycorrhizal fungi (EMF) could alter the
      susceptibility of Norway spruce (Picea abies) seedlings to root rot infection or
      necrotic foliar pathogens. Firstly, spruce seedlings were inoculated by various
      EMF and challenged with Heterobasidion isolates in triaxenix tubes. The
      ascomycete EMF Meliniomyces bicolor, that had showed strong antagonistic
      properties towards root rot causing Heterobasidion in vitro, protected spruce
      seedlings effectively against root rot. Secondly, spruce seedlings, inoculated
      with M. bicolor or the forest humus, were subjected to necrotrophic foliar
      pathogens in conventional forest nursery conditions on peat substrates. Botrytis
      cinerea infection after winter was mild and the level of needle damage was
      independent of substrate and EMF colonisation. Needle damage severity caused by
      Gremminiella abietina was high in seedlings grown in substrates with high
      nutrient availability as well as in seedlings with well-established EMF
      communities. These results show that albeit M. bicolor is able to protect spruce
      seedlings against Heterobasidion root rot in axenic cultures it fails to induce
      systemic protection against foliar pathogens. We also point out that unsterile
      inoculum sources, such as the forest humus, should not be considered for use in
      greenhouse conditions as they might predispose seedlings to unintended needle
      damages.

PMID- 29458714
TI  - Fungal communities associated with species of Fraxinus tolerant to ash dieback,
      and their potential for biological control.
AB  - Ash dieback, caused by the fungus Hymenoscyphus fraxineus, has threatened ash
      trees in Europe for more than two decades. However, little is known of how
      endophytic communities affect the pathogen, and no effective disease management
      tools are available. While European ash (Fraxinus excelsior) is severely affected
      by the disease, other more distantly related ash species do not seem to be
      affected. We hypothesise that fungal endophytic communities of tolerant ash
      species can protect the species against ash dieback, and that selected endophytes
      have potential as biocontrol agents. These hypotheses were tested by isolating
      members of the fungal communities of five tolerant ash species, and identifying
      them using ITS regions. Candidate endophytes were tested by an in vitro
      antagonistic assay with H.fraxineus. From a total of 196 isolates we identified 9
      fungal orders, 15 families, and 40 species. Fungi in orders Pleosporales, such as
      Boeremia exigua and Diaporthe spp., and Hypocreales (e.g., Fusarium sp.), were
      recovered in most communities, suggesting they are common taxa. The in vitro
      antagonistic assay revealed five species with high antagonistic activity against
      H. fraxineus. These endophytes were identified based on ITS region as
      Sclerostagonospora sp., Setomelanomma holmii, Epicoccum nigrum, B. exigua and
      Fusarium sp. Three of these taxa have been described previously as antagonists of
      plant pathogenic microbes, and are of interest for future studies of their
      potential as biological control agents against ash dieback, especially for
      valuable ash trees in parks and urban areas.

PMID- 29458715
TI  - RiArsB and RiMT-11: Two novel genes induced by arsenate in arbuscular mycorrhiza.
AB  - Plants associated with arbuscular mycorrhizal fungi (AMF) increase their
      tolerance to arsenic-polluted soils. This study aims to investigate the genes
      involved in the AMF molecular response to arsenic pollution. Genes encoding
      proteins involved in arsenic metabolism were identified and their expression
      assessed by PCR or RT-qPCR. The As-inducible gene GiArsA (R. irregularis ABC
      ATPase component of the ArsAB arsenite efflux pump) and two new genes, an
      arsenate/arsenite permease component of ArsAB (RiArsB) and a methyltransferase
      type 11 (RiMT-11) were induced when arsenate was added to two-compartment in
      vitro monoxenic cultures of R. irregularis-transformed carrot roots. RiArsB and
      RiMT-11 expression in extraradical hyphae in response to arsenate displayed
      maximum induction 4-6 h after addition of 350 MUM arsenate. Their expression was
      also detected in colonized root tissues grown in pots, or in the root-fungus
      compartment of two-compartment in vitro systems. We used a Medicago truncatula
      double mutant (mtpt4/mtpt8) to demonstrate that RiMT-11 and RiArsB transcripts
      accumulate in response to the addition of arsenate but not in response to
      phosphate. These results suggest that these genes respond to arsenate addition
      regardless of non-functional Pi symbiotic transport, and that RiMT-11 may be
      involved in arsenate detoxification by methylation in AMF-colonized tissues.

PMID- 29458716
TI  - Selection is required for efficient Cas9-mediated genome editing in Fusarium
      graminearum.
AB  - Genome engineering using Clustered Regularly Interspaced Short Palindromic
      Repeats (CRISPR)-associated nucleases, such as Cas9 (CRISPR-associated protein
      9), are revolutionising molecular biology. In this study, we established a Cas9
      based genome editing system in Fusarium graminearum, a highly destructive fungal
      pathogen of cereal crops. Although the molecular toolkit of F. graminearum is
      well developed compared to other fungi, Cas9-mediated engineering offers a number
      of potential benefits, such as the ability to create marker free mutants in this
      species. Here we have used a codon-optimised Cas9 nuclease and dual ribozyme
      based expression of a single guide RNA (sgRNA) to induce mutations. Cas9-mediated
      mutations were identified through a fungicide resistance-based phenotypic screen,
      which selects for null mutations in the FgOs1 gene encoding an osmosensor
      histidine kinase. In the absence of selection, however, mutations were identified
      at very low frequency. Examination of the mutant alleles identified suggests
      that, a microhomology-mediated end joining (MMEJ) DNA repair pathway is likely to
      be the predominant process involved in erroneous repairing of Cas9-induced double
      stranded breaks in F. graminearum.

PMID- 29458717
TI  - Suitability of dried herbarium specimens for NMR metabolomics of mushrooms. A
      comparison of four species of the genera Kuehneromyces and Hypholoma
      (Strophariaceae).
AB  - Herbarium specimens are a treasure trove for biochemical studies. However, this
      implies understanding of the chemical changes during the drying and storage of
      the specimen. We compared herbarium specimens at different ages and fresh samples
      of four mushroom species (Kuehneromyces mutabilis, Hypholoma capnoides,
      Kuehneromyces lignicola, Hypholoma fasciculare) of two genera in the family
      Strophariaceae by using proton nuclear magnetic resonance (1H NMR) spectroscopy
      combined with principal component analysis (PCA). 25 metabolites were identified.
      No significant alterations were found between herbarium samples at different
      ages, suggesting that they are stable enough for comparative studies. The most
      dominant differences between fresh and herbarium samples was that sugars such as
      alpha-alpha-trehalose, and fumaric and malic acids were more abundant in fresh
      fungi. Total contents of fatty and amino acids, uracil and gamma-aminobutyric
      acid (GABA) were higher in herbarium specimens. In addition, pyroglutamic acid
      was observed only in Kuehneromyces mutabilis and fasciculic acid E in
      Hypholomafasciculare. Hence, based on results of the studied taxa, we conclude
      that NMR metabolomics can be used for both fresh and dried mushrooms when such
      alterations are properly addressed.

PMID- 29458718
TI  - Frequent diploidisation of haploid Armillaria ostoyae strains in an outdoor
      inoculation experiment.
AB  - Very little is known about the biology and ecology of haploid Armillaria strains
      in nature. In this outdoor inoculation experiment, we assessed the virulence of
      six haploid Armillariaostoyae strains along with their diploid parent towards 2
      year-old seedlings and 4-year-old saplings of Norway spruce (Picea abies), and
      determined their ability to colonise freshly cut stumps. As inoculum source an
      Armillaria-colonised hazelnut (Corylus avellana) stem segment was inserted into
      the soil substrate. Re-isolations from mycelial fans at the root collar of
      infected trees or stumps were made. Surprisingly, not a single haploid re-isolate
      could be recovered. Microsatellite genotyping of 133 re-isolates suggests that
      the inoculated haploid strains were diploidised either by mating propagules
      (basidiospores or haploid mycelia) already present in the soil substrate or
      naturally disseminated in the course of the experiment from nearby forests.
      Consequently, no conclusion about the infectious ability of haploid Armillaria
      mycelia under natural conditions can be drawn. Nonetheless, the diploid half-sib
      families resulting from the diploidisation showed varying degrees of virulence,
      with a high correlation between the experiment with 2-year-old seedlings and 4
      year-old saplings. Despite extensive genotyping of re-isolates, no evidence for
      somatic recombination between haploid mating propagules and diploidised mycelia
      was detected, suggesting that this is an uncommon phenomenon in A. ostoyae.

PMID- 29458719
TI  - Culture degeneration in conidia of Beauveria bassiana and virulence determinants
      by proteomics.
AB  - The quality of Beauveria bassiana conidia directly affects the virulence against
      insects. In this study, continuous subculturing of B. bassiana on both rice
      grains and potato dextrose agar (PDA) resulted in 55 and 49 % conidial yield
      reduction after 12 passages and 68 and 60 % virulence reduction after 20 and 12
      passages at four d post-inoculation, respectively. The passage through Tenebrio
      molitor and Spodoptera exigua restored the virulence of rice and PDA subcultures,
      respectively. To explore the molecular mechanisms underlying the conidial quality
      and the decline of virulence after multiple subculturing, we investigated the
      conidial proteomic changes. Successive subculturing markedly increased the
      protein levels in oxidative stress response, autophagy, amino acid homeostasis,
      and apoptosis, but decreased the protein levels in DNA repair, ribosome
      biogenesis, energy metabolism, and virulence. The nitro blue tetrazolium assay
      verified that the late subculture's colony and conidia had a higher oxidative
      stress level than the early subculture. A 2A-type protein phosphatase and a
      Pleckstrin homology domain protein Slm1, effector proteins of the target of
      rapamycin (TOR) complex 1 and 2, respectively, were dramatically increased in the
      late subculture. These results suggest that TOR signalling might be associated
      with ageing in B. bassiana late subculture, in turn affecting its physiological
      characteristics and virulence.

PMID- 29458720
TI  - Metabolite production by species of Stemphylium.
AB  - Morphology and phylogeny have been used to distinguish members of the plant
      pathogenic fungal genus Stemphylium. A third method for distinguishing species of
      fungi is by chemotaxonomy. The main goal of the present study was to investigate
      the chemical potential of Stemphylium via HPLC-UV-MS analysis, while also
      exploring the potential of chemotaxonomy as a robust identification method for
      Stemphylium. Several species were found to have species-specific metabolites,
      while other species were distinguishable by a broader metabolic profile rather
      than specific metabolites. Many previously described metabolites were found to be
      important for distinguishing species, while some unknown metabolites were also
      determined to have important roles in distinguishing species of Stemphylium. This
      study is the first of its kind to investigate the chemical potential of
      Stemphylium across the whole genus.

PMID- 29458722
TI  - Molecular phylogeny of the Laboulbeniomycetes (Ascomycota).
AB  - A first molecular-based phylogeny is presented for the Laboulbeniomycetes, a
      group of ascomycete fungi that utilize arthropods for nutrition and/or dispersal.
      Morphological diversification and life-history evolution has made it difficult to
      resolve relationships within the group, and to identify close relatives. Here, we
      infer a preliminary phylogeny based on acquisition of 51 new SSU rDNA sequences,
      representing a total of 65 taxa. The results of this study demonstrate that
      Laboulbeniomycetes is monophyletic, and related to Sordariomycetes. The class
      could be divided into at least 4 or 5 orders, though we refrain from formally
      giving names to these at this stage. Further evidence for the occurrence of
      asexuality within the class is provided by the inclusion of the genera
      Chantransiopsis and Tetrameronycha, both known only as asexual taxa with thalli
      consisting of linearly superposed cells. The precise placement of the genus
      Herpomyces (Herpomycetaceae), on cockroaches, remains unresolved in our analysis,
      but lies outside of the main clade of sexually reproducing Laboulbeniales. There
      is good support for this latter grouping, comprising taxa that are found on both
      aquatic and terrestrial hosts. Within this large assemblage, we recognize 5
      distinct clades (clades E, F, G, H, I). Relationships among the so-called
      "aquatic genera" (= Ceratomycetaceae + some Euceratomycetaceae and Zodiomyces)
      are poorly resolved in our analyses, accounting for 3 of these clades (E, F, G),
      with the remainder of the taxa (largely equivalent to Laboulbeniaceae) split into
      two major groupings (clades H, I). Across all taxa, antheridial characteristics,
      features on which the earliest classifications were based, are shown to be
      homoplastic. On the other hand, features of perithecial development show an
      overall trend towards reduction, and appear to be phylogenetically informative.
      Morphological characters are identified that support the dichotomy in the
      Laboulbeniaceae and subclades within the two major groupings are discussed
      further in light of information on thallus morphology, development, and host
      relationships.

PMID- 29458723
TI  - Immunology and systemic sclerosis - Editorial.

PMID- 29458721
TI  - Galleria melonella as an experimental in vivo host model for the fish-pathogenic
      oomycete Saprolegnia parasitica.
AB  - Oomycetes are eukaryotic pathogens infecting animals and plants. Amongst them
      Saprolegnia parasitica is a fish pathogenic oomycete causing devastating losses
      in the aquaculture industry. To secure fish supply, new drugs are in high demand
      and since fish experiments are time consuming, expensive and involve animal
      welfare issues the search for adequate model systems is essential. Galleria
      mellonella serves as a heterologous host model for bacterial and fungal
      infections. This study extends the use of G. mellonella for studying infections
      with oomycetes. Saprolegniales are highly pathogenic to the insects while in
      contrast, the plant pathogen Phytophthora infestans showed no pathogenicity.
      Melanisation of hyphae below the cuticle allowed direct macroscopic monitoring of
      disease progression. However, the melanin response is not systemic as for other
      pathogens but instead is very local. The mortality of the larvae is dose
      dependent and can be induced by cysts or regenerating protoplasts as an
      alternative source of inoculation.

PMID- 29458724
TI  - The Evolving Spectrum of the Epidemiology of Thalassemia.
AB  - The thalassemias and other inherited disorders of hemoglobin are likely to remain
      a serious global health problem for the foreseeable future. Currently, they are
      most frequent in the tropical belt; an assessment of their true frequency and the
      likely cost of management for the governments of these countries will require a
      form of micromapping. Over recent years, there has been major progress toward
      better prevention and management of the thalassemias in richer countries; it is
      likely that, using the tools of molecular genetics, they will eventually be
      completely curable, although this is probably a long time in the future.

PMID- 29458725
TI  - Molecular Basis and Genetic Modifiers of Thalassemia.
AB  - Thalassemia is a disorder of hemoglobin characterized by reduced or absent
      production of one of the globin chains in human red blood cells with relative
      excess of the other. Impaired synthesis of beta-globin results in beta
      thalassemia, whereas defective synthesis of alpha-globin leads to alpha
      thalassemia. Despite being a monogenic disorder, thalassemia exhibits remarkable
      clinical heterogeneity that is directly related to the intracellular imbalance
      between alpha- and beta-like globin chains. Novel insights into the genetic
      modifiers have contributed to the understanding of the correlation between
      genotype and phenotype and are being explored as therapeutic pathways to cure
      this life-limiting disease.

PMID- 29458726
TI  - Clinical Classification, Screening and Diagnosis for Thalassemia.
AB  - At present, thalassemia diseases are classified into transfusion-dependent
      thalassemia and non-transfusion-dependent thalassemia. This classification is
      based on the clinical severity of patients determining whether they do require
      regular blood transfusions to survive (transfusion-dependent thalassemia) or not
      (non-transfusion-dependent thalassemia). In addition to the previous terminology
      of "thalassemia major" or "thalassemia intermedia," this classification has
      embraced all other forms of thalassemia syndromes such as alpha-thalassemia,
      hemoglobin E/beta-thalassemia and combined alpha- and beta-thalassemias.
      Definitive diagnosis of thalassemia and hemoglobinopathies requires a
      comprehensive workup from complete blood count, hemoglobin analysis, and
      molecular studies to identify mutations of globin genes.

PMID- 29458728
TI  - Clinical Complications and Their Management.
AB  - The hallmarks of thalassemias are ineffective erythropoiesis and peripheral
      hemolysis leading to a cascade of events responsible for several clinical
      complications. This pathophysiologic mechanism can be partially controlled by
      blood transfusions or by correction of the severity of ineffective
      erythropoiesis. Thalassemias include a spectrum of phenotypes. Two main groups
      can be clinically distinguished: transfusion-dependent (TDT) and non-transfusion
      dependent (NTDT) thalassemia. Both conditions are characterized by several
      clinical complications along life; some are shared, whereas some have higher
      prevalence in one group over the other. The authors present the most common
      clinical complications in TDT and NTDT and their management.

PMID- 29458727
TI  - Ineffective Erythropoiesis: Anemia and Iron Overload.
AB  - Stress erythropoiesis (SE) is characterized by an imbalance in erythroid
      proliferation and differentiation under increased demands of erythrocyte
      generation and tissue oxygenation. beta-thalassemia represents a chronic state of
      SE, called ineffective erythropoiesis (IE), exhibiting an expansion of erythroid
      progenitor pool and deposition of alpha chains on erythrocyte membranes, causing
      cell death and anemia. Concurrently, there is a decrease in hepcidin expression
      and a subsequent state of iron overload. There are substantial investigative
      efforts to target increased iron absorption under IE. There are also avenues for
      targeting cell contact and signaling within erythroblastic islands under SE, for
      therapeutic benefits.

PMID- 29458729
TI  - Hypercoagulability and Vascular Disease.
AB  - The presence of a high incidence of thrombotic events, mainly in nontransfusion
      dependent beta-thalassemia syndromes, has led to the identification of a
      hypercoagulable state in thalassemia patients. This article highlights the
      mechanisms leading to hypercoagulability in thalassemia. It also discusses the
      clinical experience and available evidence on prevention and management
      approaches.

PMID- 29458730
TI  - Interaction of Transfusion and Iron Chelation in Thalassemias.
AB  - The relationship between blood transfusion intensity, chelatable iron pools, and
      extrahepatic iron distribution is described in thalassemia. Risk factors for
      cardiosiderosis are discussed with particular reference to the balance of
      transfusional iron loading rate and transferrin-iron utilization rate as marked
      by plasma levels of soluble transferrin receptors. Low transfusion regimens
      increase residual erythropoiesis allowing for apotransferrin-dependent clearance
      of non-transferrin-bound iron species otherwise destined for myocardium. The
      impact of transfusion rates on chelation dosing required for iron balance is also
      shown.

PMID- 29458731
TI  - Iron Chelation Therapy as a Modality of Management.
AB  - Introduction of MRI techniques for identifying and monitoring tissue iron
      overload and the current understanding of iron homeostasis in transfusion
      dependent (TDT) and non-transfusion-dependent thalassemia have allowed for a more
      robust administration of iron chelation therapies. The development of safe and
      efficient oral iron chelators and the insights gained from large-scale
      prospective studies using these agents have improved iron overload management. A
      significant reduction in iron toxicity-induced morbidity and mortality and
      improvements in quality of life were observed in TDT. The appropriate management
      of tissue-specific iron loading in TDT has been portrayed using evidence-based
      data obtained from investigational studies.

PMID- 29458732
TI  - MRI for Iron Overload in Thalassemia.
AB  - MRI is a key tool in the current management of patients with thalassemia. Given
      its capability of assessing iron overload in different organs noninvasively and
      without contrast, it has significant advantages over other metrics, including
      serum ferritin. Liver iron concentration can be measured either with relaxometry
      methods T2*/T2 or signal intensity ratio techniques. Myocardial iron can be
      assessed in the same examination through T2* imaging. In this review, we focus on
      showing how MRI evaluates iron in both organs and the clinical applications as
      well as practical approaches to using this tool by clinicians taking care of
      patients with thalassemia.

PMID- 29458733
TI  - Fertility and Pregnancy in Women with Transfusion-Dependent Thalassemia.
AB  - As more women with transfusion-dependent thalassemia are seeking pregnancy,
      ensuring the best outcomes for both the mother and baby requires concerted,
      collaborative efforts between practitioners and the family. Proactive counseling,
      early fertility evaluation, recent developments in reproductive technology, and
      optimal management of iron overload, have resulted in more successful pregnancies
      and the birth of healthy newborns. With advances in technology for prenatal
      screening and increased awareness to perform screening for hemoglobinopathies,
      healthy pregnancy outcomes have become the expectation. Topics that require
      further study include management that allows fertility preservation, improved non
      invasive prenatal diagnosis methods for affected fetuses, the use of chelation
      therapy during pregnancy, and indications for and duration of anticoagulation.

PMID- 29458734
TI  - Hematopoietic Stem Cell Transplantation in Thalassemia.
AB  - Although recent advances in gene therapy are expected to increase the chance of
      disease cure in thalassemia major, at present hematopoietic stem cell
      transplantation (HSCT) remains the only consolidated curative approach for this
      disorder. The widest experience has been obtained in the HLA-matched family donor
      (MFD) setting, with probabilities of overall and thalassemia-free survival
      exceeding 90% and 85%, respectively. As for most patients a suitable MFD is not
      available, alternative donors (HLA-matched unrelated donor, unrelated cord blood,
      HLA-haploidentical relative) have been increasingly explored, translating into
      the expansion of the number of patients treatable with HSCT.

PMID- 29458735
TI  - Gene Therapy and Genome Editing.
AB  - The beta-thalassemias are inherited blood disorders that result from insufficient
      production of the beta-chain of hemoglobin. More than 200 different mutations
      have been identified. beta-Thalassemia major requires life-long transfusions. The
      only cure for severe beta-thalassemia is to provide patients with hematopoietic
      stem cells. Globin gene therapy promises a curative autologous stem cell
      transplantation without the immunologic complications of allogeneic
      transplantation. The future directions of gene therapy include enhancement of
      lentiviral vector-based approaches, fine tuning of the conditioning regimen, and
      the design of safer vectors. Progress in genetic engineering bodes well for
      finding a cure for severe globin disorders.

PMID- 29458737
TI  - Erratum.

PMID- 29458738
TI  - Thalassemia.

PMID- 29458736
TI  - Emerging Therapies.
AB  - At present, the only definitive cure for beta-thalassemia is a bone marrow
      transplant (BMT); however, HLA-blood-matched donors are scarcely available.
      Current therapies undergoing clinical investigation with most potential for
      therapeutic benefit are the beta-globin gene transfer of patient-specific
      hematopoietic stem cells followed by autologous BMT. Other emerging therapies
      deliver exogenous regulators of several key modulators of erythropoiesis or iron
      homeostasis. This review focuses on current approaches for the treatment of
      hemoglobinopathies caused by disruptions of beta-globin.

PMID- 29458739
TI  - ?

PMID- 29458740
TI  - Sensitivity and specificity of Frontal Assessment Battery in newly diagnosed and
      untreated obstructive sleep apnea patients.
AB  - BACKGROUND: Executive dysfunction (ED) is often observed in subjects diagnosed
      with obstructive sleep apnea (OSA), but their assessment requires facilities that
      are not always available. We aim to evaluate the extent to which Frontal
      Assessment Battery (FAB) discriminates ED in newly diagnosed, untreated, and
      without-comorbidity OSA patients. METHODS: Sixty subjects participated in the
      study. Of these, 40 (31 males and 9 females) were newly diagnosed for OSA through
      full-night polysomnography (apnea/hypopnea index; M = 39.01, SD = 27.16),
      untreated, with a mean age of 54.50 years (SD = 8.90), while the remaining 20 (15
      males and 5 females) had no symptoms of OSA (M = 51.60 years, SD = 10.70). The
      instruments used were the following: Questionnaire for Sleep Apnea Risk, Epworth
      Sleepiness Scale, Mini-Mental State Examination, and FAB. RESULTS: The group with
      OSA exhibited significantly lower values in the FAB global score (p = 0.003) and
      in Conceptualization (p = 0.001) and Mental Flexibility (p = 0.009) subtests. ROC
      analysis showed adequate discriminative capacity for the FAB global score (AUC =
      0.74) and for Conceptualization (AUC = 0.75) and Mental Flexibility (AUC = 0.70)
      scores. CONCLUSIONS: The FAB is a short and no-time-consuming tool that can be
      used to investigate the presence of ED in untreated OSA patients with no
      comorbidities, providing clinicians with a simple and effective way of detecting
      the presence of this dysfunction and allowing a more informed decision for the
      need of a full neuropsychological assessment.

PMID- 29458741
TI  - Sleep-disordered breathing is associated with disturbed cardiac repolarization in
      patients with a coronary artery bypass graft surgery.
AB  - BACKGROUND: The development of malignant ventricular arrhythmias due to abnormal
      cardiac repolarization is a major complication after coronary artery bypass graft
      surgery (CABG). Sleep-disordered breathing (SDB) is linked to prolonged cardiac
      repolarization in non-surgical patients. This study evaluates cardiac
      repolarization in patients with and without SDB who underwent CABG. METHODS: 100
      patients who had received CABG (84% men, age 68 +/- 10 years, body-mass-index
      [BMI] 28.7 +/- 4.2 kg/m2) were retrospectively evaluated. Polygraphy was recorded
      the night before CABG. SDB was defined as an apnea-hypopnea index (AHI) of >=15/h
      and differentiated into central (CSA) and obstructive (OSA) sleep apnea. Cardiac
      repolarization was assessed by means of T-peak-to-end (TpTe) and QTc-intervals
      and TpTe/QT-ratios derived from 12-lead electrocardiography (ECG). RESULTS: 37%
      of patients had SDB, 14% CSA and 23% OSA. Before CABG, patients with CSA and OSA
      had longer TpTe intervals than those without SDB (TpTe: CSA 100 +/- 26 vs. OSA 97
      +/- 19 vs. no SDB 85 +/- 14 ms, p = 0.013). QTc intervals and TpTe/QT ratios
      differed between the two groups (QTc: 444 +/- 54 vs. 462 +/- 36 vs. 421 +/- 32
      ms, p < 0.001; TpTe/QT ratio: 0.24 +/- 0.04 vs. 0.23 +/- 0.05 vs. 0.21 +/- 0.03,
      p = 0.045). SDB was associated with abnormal cardiac repolarization independent
      of known risk factors for cardiac arrhythmias, such as age, sex, BMI, N-terminal
      pro-brain-natriuretic-peptide (NT-proBNP), and heart failure (TpTe: B-coefficient
      [95%CI]: 16.0, [7.6-24.3], p < 0.001; QTc: 27.2 [9.3-45.1], p = 0.003; TpTe/QT
      ratio: 2.9 [1.2-4.6], p < 0.001). CONCLUSION: Independent of known risk factors
      for cardiac arrhythmias, SDB was significantly associated with abnormal cardiac
      repolarization before CABG. Data suggest that SDB may contribute to an increased
      risk of ventricular arrhythmias after CABG.

PMID- 29458742
TI  - Preserved sleep microstructure in blind individuals.
AB  - The loss of vision, particularly when it occurs early in life, is associated with
      compensatory cortical plasticity not only in the visual cortical areas, but
      throughout the entire brain. The absence of visual input to the retina can also
      induce changes in entrainment of the circadian rhythm, as light is the primary
      zeitgeber of the master biological clock found in the suprachiasmatic nucleus of
      the hypothalamus. In addition, a greater number of sleep disturbances is often
      reported in blind individuals. Here, we examined various electroencephalographic
      microstructural components of sleep, both during rapid-eye-movement (REM) sleep
      and non-REM (NREM) sleep, between blind individuals, including both of early and
      late onset, and normal-sighted controls. During wakefulness, occipital alpha
      oscillations were lower, or absent in blind individuals. During sleep,
      differences were observed across electrode derivations between the early and late
      blind samples, which may reflect altered cortical networking in early blindness.
      Despite these differences in power spectra density, the electroencephalography
      microstructure of sleep, including sleep spindles, slow wave activity, and
      sawtooth waves, remained present in the absence of vision.

PMID- 29458743
TI  - Sleep disturbance as a predictor of time to drug and alcohol use treatment in
      primary care.
AB  - BACKGROUND: Sleep Disturbances (SDs) are a symptom common to mental health
      disorders (MHD) and substance use disorders (SUD). We aimed to identify the value
      of SD as a predictor for subsequent treatment of illicit drug and alcohol use
      disorders (SUDs) in primary care and relative to the predictive value of mental
      health disorders (MHDs). METHODS: We used electronic health records data from
      ambulatory primary care in a safety net Boston area healthcare system from 2013
      to 2015 (n = 83,920). SUD (separated into illicit drug use disorder and alcohol
      use disorder) and MHD were identified through ICD-9 codes and medical record
      documentation. We estimated Cox proportional hazard models to examine the risk of
      SUD across four comparison groups (SD only, SD and MHD, MHD only, and neither SD
      nor MHD). RESULTS: Compared to patients with no sleep or MHD, patients with SD
      had a greater risk for subsequent SUD treatment. Approximately one-fifth of
      patients with SD were treated for an illicit drug use disorder and approximately
      12% were treated for alcohol use disorder. Risk for SUD treatment, estimated at
      over 30% by the end of the study, was greatest for patients with a MHD, either
      alone or comorbid with SD. Risk was greater for older patients and men, and lower
      for minority patients. CONCLUSIONS: SD and MHD, individually and comorbid,
      significantly predict subsequent treatment of illicit drug and alcohol use
      disorder in primary care. Screening and evaluation for SD should be a routine
      practice in primary care to help with identifying potential SUD risk.

PMID- 29458745
TI  - Sleep duration independently influences metabolic body size phenotype in children
      and adolescents: a population-based study.
AB  - BACKGROUND: Epidemiologic studies have found an association between sleep
      duration and obesity. However, the relationship between sleep duration and
      metabolic body size phenotype in children and adolescents remains unknown.
      METHODS: In this cross-sectional study, 3650 participants (1946 boys and 1704
      girls) from the Korean National Health and Nutrition Examination Survey 2007-2012
      were classified into four phenotypes according to body mass index and metabolic
      heath status based on the definition of metabolic syndrome by NCEP-ATP III or the
      International Diabetes Federation. The four phenotypes were: metabolically
      healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW),
      metabolically healthy overweight (MHO), and metabolically unhealthy overweight
      (MUO). The associations between the four metabolic body size phenotypes and sleep
      duration, categorized as very short (<=5 h), short (6-7 h), normal (8-10 h), or
      long (>=11 h), were evaluated. RESULTS: Sleep duration was shorter in the MUO
      group (7.0 +/- 1.5 h) than in the MHNW (7.3 +/- 1.4 h) or MUNW (7.8 +/- 1.6 h)
      groups. After adjusting for age, sex, household income, and physical activity,
      compared with a normal sleep duration, very short sleep duration (<=5 h) was
      associated with a higher prevalence of being overweight/obese (26.4% vs 17.4%, p
      = 0.001), lower risk of being MHNW (0.711 (0.538-0.940), p = 0.017) or MUNW
      (0.478 (0.237-0.962), p = 0.039), and higher risk of being MHO (1.702 (1.193
      2.428), p = 0.003). By contrast, long sleep duration (>=11 h) was associated with
      a higher risk of being MUNW (2.581 (1.124-5.928), p = 0.025). CONCLUSIONS: Sleep
      duration may be independently associated with metabolic body size phenotype in
      children and adolescents.

PMID- 29458744
TI  - Alcohol and the risk of sleep apnoea: a systematic review and meta-analysis.
AB  - OBJECTIVE: A systematic review and meta-analysis of the association between
      alcohol consumption and risk of sleep apnoea in adults. METHODS: We searched
      Medline, EMBASE and Web of Science databases from 1985 to 2015 for comparative
      epidemiological studies assessing the relation between alcohol consumption and
      sleep apnoea. Two authors independently screened and extracted data. Random
      effects meta-analysis was used to estimate pooled effect sizes with 95%
      confidence intervals (CI). Heterogeneity was quantified using I2 and explored
      using subgroup analyses based on study exposure and outcome measures, quality,
      design, adjustment for confounders and geographical location. Publication bias
      was assessed using a funnel plot and Egger's test. RESULTS: We identified 21
      studies from which estimates of relative risk could be obtained. Meta-analysis of
      these estimates demonstrated that higher levels of alcohol consumption increased
      the risk of sleep apnoea by 25% (RR 1.25, 95%CI 1.13-1.38, I2 = 82%, p < 0.0001).
      This estimate's differences were robust in alcohol consumption and sleep apnoea
      definitions, study design, and quality but was greater in Low and Middle Income
      Country locations. We detected evidence of publication bias (p = 0.001). A
      further eight included studies reported average alcohol consumption in people
      with and without sleep apnoea. Meta-analysis revealed that mean alcohol intake
      was two units/week higher in those with sleep apnoea, but this difference was not
      statistically significant (p = 0.41). CONCLUSION: These findings suggest that
      alcohol consumption is associated with a higher risk of sleep apnoea, further
      supporting evidence that reducing alcohol intake is of potential therapeutic and
      preventive value in this condition.

PMID- 29458746
TI  - Stridor combined with other sleep breathing disorders in multiple system atrophy:
      a tailored treatment?
AB  - OBJECTIVES: To determine the frequency of sleep breathing disorders in multiple
      systemic atrophy (MSA, combining Parkinsonism, cerebellar syndrome, and
      dysautonomia) and evaluate the benefit/tolerance of various modes of ventilation.
      METHODS: We retrospectively analyzed 45 patients with MSA having undergone a
      videopolysomnography. Their sleep characteristics were compared to those of 45
      patients with Parkinson's disease and 45 healthy controls, matched for age and
      sex. Patients with MSA received fixed continuous positive airway pressure (CPAP)
      when stridor was isolated, auto-adjusting CPAP when it was combined with
      obstructive sleep apnea, and adaptive servo-ventilation (ASV) when combined with
      central sleep apnea. RESULTS: Higher periodic leg movements index and more
      frequent REM sleep behavior disorder were observed in MSA patients, compared to
      patients with Parkinson's disease and healthy controls. In MSA, 28/45 (62.2%)
      patients had sleep breathing disorders, including (overlapping samples) stridor
      (n = 17, 38%), obstructive sleep apnea (n = 14, 31%), central sleep apnea (n = 4,
      9%), and ataxic breathing (n = 1). Except for three initial refusals and two yet
      untreated patients, fixed CPAP (n = 9), auto-adjusting CPAP (n = 8) and ASV (n =
      2) were well-tolerated (limited leaks and good compliance) and successfully
      controlled stridor plus sleep apnea. Treated patients had survival times similar
      to those of patients without any sleep breathing disorder. CONCLUSION: In this
      small group, tailored management of stridor in MSA as an independent issue or
      combined with obstructive and central sleep apnea, yields a survival similar to
      survival in patients without sleep breathing disorders.

PMID- 29458747
TI  - Sex-specific associations between extreme sleep duration and prevalence of cardio
      cerebral vascular disease: a community-based cross-sectional study.
AB  - BACKGROUND: Most previous studies on sleep duration and cardio-cerebral vascular
      disease (CCVD) association have not adequately controlled for many confounders.
      The current study prospectively examined the association of sleep duration with
      CCVD prevalence in a Chinese community population; cardiovascular risk factors,
      chronic diseases, and sleep quality were taken into consideration. METHODS: A
      cross-sectional study conducted in Pudong New Area of Shanghai, China. Through
      three-stage sampling, 10,657 adults aged >=15 years were randomly selected. Self
      reported sleep duration and CCVD prevalence were obtained using a structured
      questionnaire. Medical records of the subjects were reviewed by investigators for
      further confirmation. Relationships between sleep duration and CCVD prevalence
      were examined using logistic regression models. RESULTS: Compared to midrange
      sleep duration (7 h), the multivariate-adjusted OR of CCVD prevalence was 1.550
      (95% CI 1.192-2.017) for sleeping 5 h, 1.427 (95% CI 0.983-2.072) for sleeping <5
      h. A similar situation also prevailed in coronary heart disease (CHD) prevalence:
      the multivariate-adjusted OR of stroke prevalence was 2.130 (95% CI 1.338-3.389)
      for sleeping >9 h. In an analysis stratified by sex, participants with a long
      sleep duration (>9 h) demonstrated significantly increased prevalence (OR =
      3.623, 95% CI 1.862-7.052) for stroke only in men. CONCLUSIONS: The relationship
      between extreme sleep durations and CCVD were influenced by sex in a Chinese
      community population. Further studies are needed to investigate the mechanisms of
      the association between extreme sleep duration and CCVD, as well as sex
      specificity in the relationship.

PMID- 29458748
TI  - Does continuous positive airway pressure treatment affect autonomic nervous
      system in patients with severe obstructive sleep apnea?
AB  - OBJECTIVE: This study is aimed at evaluating whether Continuous Positive Airway
      Pressure treatment (CPAP) may affect autonomic nervous system (ANS) in male
      patients with severe obstructive sleep apnea (OSAS). METHODS: We compared
      autonomic symptoms of de novo severe OSAS patients, OSAS patients on chronic CPAP
      treatment and healthy controls, using the Scales for Outcome in Parkinson disease
      Autonomic (SCOPA-AUT) questionnaire. All groups underwent cardiovascular function
      tests including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, hand
      grip and cold face tests. Statistical significance was set at p < 0.05. RESULTS:
      Twelve de novo severe OSAS patients, 17 male OSAS on CPAP and 14 controls were
      studied. The mean SCOPA-AUT total score was significantly higher in de novo OSAS
      patients compared with controls. Regarding the distinct domains, both de novo
      OSAS and CPAP group had abnormalities in respect of controls in urinary sphere.
      In supine rest condition the baseline values of systolic blood pressure were
      significantly increased in untreated OSAS patients compared with controls,
      whereas the basal values of diastolic blood pressure were significantly higher in
      CPAP patients with respect to controls. After ten min of HUTT, diastolic blood
      pressure changes were significantly higher in controls compared to both OSAS
      groups. Untreated OSAS patients showed significant different responses at deep
      breathing compared to controls. Both OSAS groups had a significant reduction of
      reflex bradycardia at cold face test. CONCLUSIONS: Our study shows that both
      treated and untreated OSAS patients complain of subjective autonomic symptoms
      like other sleep disorders reinforcing the close relationship between sleep and
      autonomic activity. Furthermore, cardiovascular reflexes indicate a tendency to
      hypertension and a reduced sensitivity to stimuli during wakefulness even in OSA
      patients on CPAP treatment, suggesting potentially permanent autonomic function
      deficits.

PMID- 29458749
TI  - Efficacy of ferric carboxymaltose (FCM) 500 mg dose for the treatment of Restless
      Legs Syndrome.
AB  - INTRODUCTION: There have been four randomized, placebo-controlled, double-blinded
      studies of intravenous (IV) iron in Restless Legs Syndrome (RLS), all of which
      delivered a final total dose of 1000 mg of iron. The purpose of this study was to
      evaluate effects of a lesser total dose (500 mg of iron). METHODS: Subjects with
      idiopathic RLS were enrolled in a randomized, double-blinded, placebo-controlled
      study. Subjects received either 500 mg ferric carboxymaltose (FCM) or placebo as
      a single infusion (Phase I). Subjects who were previously on medication were off
      any RLS medications for at least two weeks prior to baseline assessment. The
      primary outcome variable was a change-from-baseline at week six on the
      International RLS Severity Scale (IRLSS) and a subject-completed Visual Analog
      Scale of Severity (VAS). Phase II of the study involved long-term (30 weeks)
      follow-up after completing the six week efficacy phase. RESULTS: At week six post
      infusion, FCM, compared to placebo recipients, showed no significantly greater
      change-from-baseline for both primary outcome measures (IRLSS scale, FCM 500 mg
      vs. placebo: -8.3 +/- 7.5 vs. -4.8 +/- 8.7, p = 0.100; VAS, FCM 500 mg vs.
      placebo: -23.4 +/- 24.1 vs. -13.3 +/- 23.1, p = 0.077). None of the secondary
      outcome variables showed a significant difference at week six. Seven (21.9%) of
      the 32 subjects treated with iron in Phase I remained free from further RLS
      medications at 30 weeks. No serious adverse effects were found in this study.
      CONCLUSIONS: This study did not show significant benefit from a single 500 mg FCM
      treatment for RLS symptoms. The two previous, well-controlled, trials of 1000 mg
      FCM showed significant treatment benefits which suggested that there may have
      been a clinically relevant total dose required to achieve a clinical response.

PMID- 29458750
TI  - Different maturational changes of fast and slow sleep spindles in the first four
      years of life.
AB  - OBJECTIVE/BACKGROUND: Massive changes in brain morphology and function in the
      first years of life reveal a postero-anterior trajectory of cortical maturation
      accompanied by regional modifications of NREM sleep. One of the most sensible
      marker of this maturation process is represented by electroencephalographic (EEG)
      activity within the frequency range of sleep spindles. However, direct evidence
      that these changes actually reflect maturational modifications of fast and slow
      spindles still lacks. Our study aimed at answering the following questions: 1. Do
      cortical changes at 11.50 Hz frequency correspond to slow spindles? 2. Do fast
      and slow spindles show different age trajectories and different topographical
      distributions? 3. Do changes in peak frequency explain age changes of slow and
      fast spindles? PATIENTS/METHODS: We measured the antero-posterior changes of slow
      and fast spindles in the first 60 min of nightly sleep of 39 infants and children
      (0-48 mo.). RESULTS: We found that (A) changes of slow spindles from birth to
      childhood mostly affect frontal areas (B) variations of fast and slow spindles
      across age groups go in opposite direction, the latter progressively increasing
      across ages; (C) this process is not merely reducible to changes of spindle
      frequency. CONCLUSIONS: As a main finding, our cross-sectional study shows that
      the first form of mature spindle (i.e., corresponding to the adult phasic event
      of NREM sleep) is marked by the emergence of slow spindles on anterior regions
      around the age of 12 months.

PMID- 29458751
TI  - Somatosensory function is impaired in patients with idiopathic REM sleep
      behaviour disorder.
AB  - BACKGROUND: Idiopathic REM sleep behaviour disorder (iRBD) has been recognised as
      a significant biomarker for developing a neurodegenerative alpha-synucleinopathy,
      which is why iRBD is considered to be a prodromal state for alpha
      synucleinopathies including Parkinson's disease (PD). Many patients with PD
      suffer from complaints of pain and present impaired somatosensory function. We
      hypothesized that pain perception and somatosensory function could be altered
      already in a preclinical stage of PD including iRBD. Hence, the objective of this
      study was to investigate pain perception and somatosensory function in patients
      with iRBD. METHODS: Quantitative sensory testing (QST), laser evoked potentials
      (LEPs), and conditioned pain modulation (CPM) testing were performed in 13 iRBD
      patients without any clinical signs of PD or narcolepsy (11 males, 2 females,
      mean age 65.2 years) and 15 gender- and age-matched healthy control subjects (12
      males, 3 females, mean age 65.8 years). RESULTS: Thermal detection thresholds
      were higher in the iRBD group compared with the control group (cold detection
      threshold (CDT) p = 0.020, thermal sensory limen (TSL) p = 0.001), indicating an
      impaired temperature sensation in iRBD patients. The N2/P2 LEPs amplitude was
      smaller in iRBD patients than controls, but not statistically significant (p =
      0.053). CONCLUSIONS: This study found an impaired somatosensory function in iRBD
      patients, suggesting that somatosensory impairment might be an early feature in
      the neurodegenerative process of PD.

PMID- 29458752
TI  - A survey on sleep questionnaires and diaries.
AB  - Sleep assessment is a fundamental part of health evaluation. In fact, many
      diseases (such as obesity, diabetes, or hypertension, as well as psychiatric,
      neurological, and cardiovascular diseases) produce sleep disorders that are often
      used as indicators, diagnosis (symptoms), or even as predictors (eg, for
      depression) of health. For this reason, many efforts have been devoted to
      designing methods to control and report on sleep quality. Two of the most used
      sleep assessment tools are sleep questionnaires and sleep diaries. Both methods
      have a very low cost are easy to administer do not require a sleep centre
      (unlike, eg, polysomnography), and can be self-administered. Most important, as
      it has been shown in recent studies, their accuracy is relatively high. In this
      survey, we systematically review and compare these tools. We examine the
      evolution of sleep questionnaires and diaries over time, and compare their
      structure and usage. We also review the validation studies and comparatives
      performed in previous studies. This allows us to compare the relative
      sensitivities and specificities of these methods. Modern sleep diaries come in
      the form of an app. Therefore, we also present the most advanced and used apps,
      and discuss their advantages over classical paper diaries.

PMID- 29458753
TI  - Challenges in sleep stage R scoring in patients with autosomal dominant
      spinocerebellar ataxias (SCA1, SCA2 and SCA3) and oculomotor abnormalities: a
      whole night polysomnographic evaluation.
AB  - OBJECTIVES: Spinocerebellar ataxias are progressive neurodegenerative disorders
      characterized by progressive cerebellar features with additional neuro-axis
      involvement. Oculomotor abnormality is one of the most frequent manifestations.
      This study was done to assess the polysomnographic abnormalities in patients with
      Spinocerebellar ataxia (SCA1, SCA2 and SCA3) and also to evaluate whether
      oculomotor abnormalities interfere with sleep stage R scoring. METHODS: The study
      was carried out using 36 genetically positive SCA patients. All patients
      underwent neurological examination with special focus on oculomotor function
      (optokinetic nystagmus-OKN and extraocular movement restriction-EOM). The sleep
      quality was measured with Pittsburgh Sleep Quality Index (PSQI) and Epworth
      Sleepiness Scale (ESS). Disease severity was assessed with International
      Cooperative Ataxia Rating Scale (ICARS). All the patients underwent over-night
      video-polysomnography (VPSG). RESULTS: Out of 36 patients studied, the data of 34
      patients [SCA1 (n = 12), SCA2 (n = 13), SCA3 (n = 9)] were used for final
      analysis. Patients from SCA1, SCA2, and SCA3 category did not show significant
      differences in age and diseases severity (ICARS). All patients had vertical OKN
      impairment. Oculomotor impairment was higher in SCA2 patients. Sleep macro
      architecture analysis showed absent stage R sleep, predominantly in SCA2 (69%)
      followed by SCA3 (44%) and SCA1 (8%). Patients showed a strong negative
      correlation of stage R sleep percentage with disease severity and oculomotor
      dysfunction. CONCLUSION: Voluntary saccadic eye movement velocity and rapid eye
      movements (REMs) in sleep are strongly correlated. The more severe the saccadic
      velocity impairment, the less likely was it to generate REMs (rapid eye
      movements) during stage R. Accordingly 69% of SCA2 patients with severe
      occulomotor impairments showed absent stage R as per the AASM sleep scoring. We
      presume that the impaired REMs generation in sleep could be due to oculomotor
      abnormality and has resulted in spuriously low or absent stage R sleep percentage
      in SCA patients with conventional VPSG scoring rules. The present study
      recommends the modification of AASM scoring rules for stage R in patients with
      oculomotor abnormalities.

PMID- 29458754
TI  - Processing of DNA Double-Strand Breaks in Yeast.
AB  - Single-stranded DNA (ssDNA) intermediates are essential for homology-dependent
      repair of DNA double-strand breaks (DSBs) and for the DNA damage response. Here
      we describe methods routinely used to identify ssDNA intermediates formed by end
      processing of site-specific DSBs in Saccharomyces cerevisiae. These methods have
      been applied in other model systems and human cell lines, and are useful tools to
      gain insight into the enzymes that process DSBs and how they are regulated.

PMID- 29458755
TI  - Direct Quantitative Monitoring of Homology-Directed DNA Repair of Damaged
      Telomeres.
AB  - Homology-directed DNA repair (HDR) is an evolutionary conserved mechanism that is
      required for genome integrity and organismal fitness across species. While a
      myriad of different factors and mechanisms are able to execute HDR, all forms
      necessitate common steps of DNA damage recognition, homology search and capture,
      and assembly of a DNA polymerase complex to conduct templated DNA synthesis. The
      central question of what determines HDR mechanism utilization in mammalian cells
      has been limited by an inability to directly monitor the DNA damage response and
      products of repair as they arise from a defined genomic lesion. In this chapter,
      we describe several methodologies to delineate major steps of HDR during
      alternative lengthening of telomeres in human cells. This includes procedures to
      visualize interchromosomal telomere homology searches in real time and
      quantitatively detect HDR synthesis of nascent telomeres emanating from
      synchronous activation of telomere DNA double-strand breaks. We highlight the
      critical details of these methods and their applicability to monitoring HDR at
      telomeres in a broad variety of mammalian cell types.

PMID- 29458756
TI  - Kinetic Analysis of the Exonuclease Activity of the Bacteriophage T4 Mre11-Rad50
      Complex.
AB  - Bacteriophage T4 encodes orthologs of the proteins Rad50 (gp46) and Mre11 (gp47),
      which form a heterotetrameric complex (MR) that is responsible for host genome
      degradation and the processing of DNA ends for recombination-dependent DNA
      repair. In this chapter, we describe the ensemble methods currently employed by
      our laboratory to characterize the exonuclease activity of the T4 MR complex. DNA
      exonucleases play a vital role in maintaining the integrity of DNA through their
      participation in DNA repair pathways and as proofreaders for DNA polymerases.
      Methods for quantifying the general features of the exonuclease, and for
      determining steady-state kinetic parameters (Km, kcat), the polarity of
      exonuclease activity, and processivity are presented. These methods should be
      applicable to all DNA exonucleases, and to some extent endonucleases.

PMID- 29458757
TI  - Expression, Purification, and Biochemical Evaluation of Human RAD51 Protein.
AB  - The RAD51 DNA strand exchange protein plays an important role in maintaining the
      integrity of the human genome. It promotes homology-directed DNA repair by
      exchanging strands between the damaged and the intact DNA molecules. It also
      plays an important role in stabilizing distressed DNA replication forks. When
      overexpressed or misregulated, however, RAD51 contributes to "rogue," genome
      destabilizing events that can lead to cancer, cell death, and to acquisition of
      chemotherapy resistance by cancerous cells. Human RAD51 is, therefore, an
      important and highly coveted anticancer drug target. Biochemical, biophysical,
      and structural studies of the human RAD51 and establishment of its structure
      activity relationship require purification of large quantities of protein. In
      this chapter we describe a robust method for expression and purification of human
      RAD51 and the methods for assessing its activity based on the single-strand DNA
      binding stoichiometry and its capacity to carry out the DNA strand exchange
      reaction.

PMID- 29458758
TI  - Determining the RAD51-DNA Nucleoprotein Filament Structure and Function by Cryo
      Electron Microscopy.
AB  - Homologous recombination is a universal tool for DNA double-strand break and
      replication fork repair, and it is catalyzed by a highly conserved family of
      recombinases. In eukaryotes, Rad51 is the recombinase that catalyzes the pairing
      of homologous DNA molecules and the exchange of strands between the paired
      molecules. Rad51 assembles on single-stranded DNA (ssDNA) stemming from lesion
      processing to form a right-handed helical polymer that engages then samples
      double-stranded DNA (dsDNA) for homology. Upon matching with a homologous
      sequence, the Rad51-bound ssDNA invades the dsDNA, leading to the formation of a
      DNA joint with concomitant displacement of the strand of like polarity. The Rad51
      DNA filaments are amenable to structural studies using cryo-electron microscopy
      (cryo-EM). In particular, recent technical breakthroughs in cryo-EM have made it
      possible to define the structure and function of human RAD51 at near-atomic
      resolution. In this chapter, we describe our cryo-EM approach to capture the
      human RAD51 filament structures in various stages of catalysis. The approach may
      also be useful for related recombinases and other helical assemblies.

PMID- 29458760
TI  - TIRF-Based Single-Molecule Detection of the RecA Presynaptic Filament Dynamics.
AB  - RecA is a key protein in homologous DNA repair process. On a single-stranded (ss)
      DNA, which appears as an intermediate structure at a double-strand break site,
      RecA forms a kilobase-long presynaptic filament that mediates homology search and
      strand exchange reaction. RecA requires adenosine triphosphate as a cofactor that
      confers dynamic features to the filament such as nucleation, end-dependent growth
      and disassembly, scaffold shift along the ssDNA, and conformational change. Due
      to the complexity of the dynamics, detailed molecular mechanisms of functioning
      presynaptic filament have been characterized only recently after the advent of
      single-molecule techniques that allowed real-time observation of each kinetic
      process. In this chapter, single-molecule fluorescence resonance energy transfer
      assays, which revealed detailed molecular pictures of the presynaptic filament
      dynamics, will be discussed.

PMID- 29458759
TI  - Observation and Analysis of RAD51 Nucleation Dynamics at Single-Monomer
      Resolution.
AB  - Human RAD51 promotes accurate DNA repair by homologous recombination and is
      involved in protection and repair of damaged DNA replication forks. The active
      species of RAD51 and related recombinases in all organisms is a nucleoprotein
      filament assembled on single-stranded DNA (ssDNA). The formation of a
      nucleoprotein filament competent for the recombination reaction, or for DNA
      replication support, is a delicate and strictly regulated process, which occurs
      through filament nucleation followed by filament extension. The rates of these
      two phases of filament formation define the capacity of RAD51 to compete with the
      ssDNA-binding protein RPA, as well as the lengths of the resulting filament
      segments. Single-molecule approaches can provide a wealth of quantitative
      information on the kinetics of RAD51 nucleoprotein filament assembly, internal
      dynamics, and disassembly. In this chapter, we describe how to set up a single
      molecule total internal reflection fluorescence microscopy experiment to monitor
      the initial steps of RAD51 nucleoprotein filament formation in real-time and at
      single-monomer resolution. This approach is based on the unique, stretched-ssDNA
      conformation within the recombinase nucleoprotein filament and follows the
      efficiency of Forster resonance energy transfer (EFRET) between two DNA
      conjugated fluorophores. We will discuss the practical aspects of the
      experimental setup, extraction of the FRET trajectories, and how to analyze and
      interpret the data to obtain information on RAD51 nucleation kinetics, the
      mechanism of nucleation, and the oligomeric species involved in filament
      formation.

PMID- 29458761
TI  - Methods to Study DNA End Resection I: Recombinant Protein Purification.
AB  - Accurate repair of DNA double-strand breaks (DSBs) is carried out by homologous
      recombination. In order to repair DNA breaks by the recombination pathway, the 5'
      terminated DNA strand at DSB sites must be first nucleolytically processed to
      produce 3'-overhang. The process is termed DNA end resection and involves the
      interplay of several nuclease complexes. DNA end resection commits DSB repair to
      the recombination pathway including a process termed single-strand annealing, as
      resected DNA ends are generally nonligatable by the competing nonhomologous end
      joining machinery. Biochemical reconstitution experiments provided invaluable
      mechanistic insights into the DNA end resection pathways. In this chapter, we
      describe preparation procedures of key proteins involved in DNA end resection in
      human cells, including the MRE11-RAD50-NBS1 complex, phosphorylated variant of
      CtIP, the DNA2 nuclease-helicase with its helicase partners Bloom (BLM) or Werner
      (WRN), as well as the single-stranded DNA-binding protein replication protein A.
      The availability of recombinant DNA end resection factors will help to further
      elucidate resection mechanisms and regulatory processes that may involve novel
      protein partners and posttranslational modifications.

PMID- 29458762
TI  - The RadA Recombinase and Paralogs of the Hyperthermophilic Archaeon Sulfolobus
      solfataricus.
AB  - Repair of DNA double-strand breaks is a critical function shared by organisms in
      all three domains of life. The majority of mechanistic understanding of this
      process has come from characterization of bacterial and eukaryotic proteins,
      while significantly less is known about analogous activities in the third,
      archaeal domain. Despite the physical resemblance of archaea to bacteria,
      archaeal proteins involved in break repair are remarkably similar to those used
      by eukaryotes. Investigating the function of the archaeal version of these
      proteins is, in many cases, simpler than working with eukaryotic homologs owing
      to their robust nature and ease of purification. In this chapter, we describe
      methods for purification and activity analysis for the RadA recombinase and its
      paralogs from the hyperthermophilic acidophilic archaeon Sulfolobus solfataricus.

PMID- 29458763
TI  - Reconstituting the 4-Strand DNA Strand Exchange.
AB  - Proteins of the Rad51 family play a key role in homologous recombination by
      carrying out DNA strand exchange. Here, we present the methodology and the
      protocols for the 4-strand exchange between gapped circular DNA and homologous
      linear duplex DNA promoted by human Rad51 and Escherichia coli RecA orthologs.
      This reaction includes formation of joint molecules and their extension by branch
      migration in a polar manner. The presented methodology may be used for
      reconstitution of the medial-to-late stages of homologous recombination in vitro
      as well as for investigation of the mechanisms of branch migration by helicase
      like proteins, e.g., Rad54, BLM, or RecQ1.

PMID- 29458764
TI  - Purification of Saccharomyces cerevisiae Homologous Recombination Proteins Dmc1
      and Rdh54/Tid1 and a Fluorescent D-Loop Assay.
AB  - Budding yeast Dmc1 is a member of the RecA family of strand exchange proteins
      essential for homologous recombination (HR) during meiosis. Dmc1 mediates the
      steps of homology search and DNA strand exchange reactions that are central to
      HR. To achieve optimum activity, Dmc1 requires a number of accessory factors.
      Although methods for purification of Dmc1 and many of its associated factors have
      been described (Binz, Dickson, Haring, & Wold, 2006; Busygina et al., 2013; Chan,
      Brown, Qin, Handa, & Bishop, 2014; Chi et al., 2006; Cloud, Chan, Grubb, Budke, &
      Bishop, 2012; Nimonkar, Amitani, Baskin, & Kowalczykowski, 2007; Van Komen,
      Macris, Sehorn, & Sung, 2006), Dmc1 has been particularly difficult to purify
      because of its tendency to aggregate. Here, we provide an alternative and simple
      high-yield purification method for recombinant Dmc1 that is active and responsive
      to stimulation by accessory factors. The same method may be used for purification
      of recombinant Rdh54 (a.k.a. Tid1) and other HR proteins with minor adjustments.
      We also describe an economical and sensitive D-loop assay for strand exchange
      proteins that uses fluorescent dye-tagged, rather than radioactive, ssDNA
      substrates.

PMID- 29458765
TI  - Probing Dynamic Assembly and Disassembly of Rad51 Tuned by Srs2 Using smFRET.
AB  - The integrity of DNA is critical for sustaining the life of any living organism,
      as DNA is a reservoir of its genetic information. However, DNA is continuously
      damaged by either normal metabolic pathways or environmental insults such as
      ultraviolet exposure or chemicals. Double-stranded DNA break is one of the most
      common types of DNA damage that requires activation of homologous recombination
      (HR) pathway mediated by Rad51 in eukaryotes (Paques & Haber, 1999; Symington,
      2002). Rad51 protein forms a helical nucleoprotein filament on resected DNA to
      initiate homology search but also can interact with other single-stranded DNA
      (ssDNA)-binding proteins including Srs2. Srs2, a well-known antirecombinase in
      HR, is an ATP-dependent 3'-5' DNA helicase in the budding yeast Saccharomyces
      cerevisiae as well as an ssDNA translocase. It disrupts Rad51 filaments,
      preventing HR (Krejci et al., 2003; Le Breton et al., 2008; Veaute et al., 2003).
      In the following text, we provide detailed experimental platforms employed to
      investigate the activity of Rad51 and Srs2 using single-molecule Forster
      resonance energy transfer and protein-induced fluorescence enhancement. First, we
      demonstrate how to detect Rad51 filament formation to address the binding site
      size binding kinetic of the Rad51, as well as the directionality of the filament
      formation. Next, we explain how to visualize ATP-dependent translocation and
      unwinding activities of Srs2 on DNA. Lastly, we demonstrate the filament forming
      activity by Rad51 which is counteracted by the filament removal activity of Srs2.

PMID- 29458766
TI  - The Recombination Mediator BRCA2: Architectural Plasticity of Recombination
      Intermediates Revealed by Single-Molecule Imaging (SFM/TIRF).
AB  - Cellular functions are defined by dynamic assembly, rearrangement, and
      disassembly of biomolecules to achieve control and specificity. As an example,
      effective DNA repair is brought about by the concerted action of several DNA
      processing proteins. Both changes in the structure of individual proteins and in
      the arrangement of multiple proteins together (referred to here as architecture)
      are inherent to biological function. These dynamic changes are exemplified in the
      breast cancer susceptibility protein 2 (BRCA2). BRCA2 is a DNA repair protein
      that undergoes changes in its own structure and affects changes in molecular
      architecture with partners during homologous recombination (HR) repair of DNA
      double strand breaks. These challenging features of BRCA2 protein, its size and
      predicted stretches of intrinsically disordered regions, have made it difficult
      to determine the structural consequences and mechanistic importance of
      interactions between full-length BRCA2 with RAD51 and other HR proteins. In this
      chapter, we describe scanning force microscopy (SFM)-based approaches to study
      DNA-protein complexes involved in HR, the architectural plasticity of full-length
      BRCA2, and the dynamic reorganization of these molecular components associated
      with essential steps of HR.

PMID- 29458767
TI  - Single-Molecule Dynamics and Localization of DNA Repair Proteins in Cells.
AB  - Direct observation of individual protein molecules in their native environment,
      at nanometer resolution, in a living cell, in motion is not only fascinating but
      also uniquely informative. Several recent major technological advances in genomic
      engineering, protein and synthetic fluorophore development, and light microscopy
      have dramatically increased the accessibility of this approach. This chapter
      describes the procedures for modifying endogenous genomic loci to producing
      fluorescently tagged proteins, their high-resolution visualization, and analysis
      of their dynamics in mammalian cells, using DNA repair proteins BRCA2 and RAD51
      as an example.

PMID- 29458768
TI  - Single-Stranded DNA Curtains for Studying the Srs2 Helicase Using Total Internal
      Reflection Fluorescence Microscopy.
AB  - Helicases are crucial participants in many types of DNA repair reactions,
      including homologous recombination. The properties of these enzymes can be
      assayed by traditional bulk biochemical analysis; however, these types of assays
      cannot directly access some types of information. In particular, bulk biochemical
      assays cannot readily access information that may be obscured in population
      averages. Single-molecule assays offer the potential advantage of being able to
      visualize the molecules in question in real time, thus providing direct access to
      questions relating to translocation velocity, processivity, and insights into how
      helicases may behave on different types of substrates. Here, we describe the use
      of single-stranded DNA (ssDNA) curtains as an assay for directly viewing the
      behavior of the Saccharomyces cerevisiae Srs2 helicase on single molecules of
      ssDNA. When used with total internal reflection fluorescence microscopy, these
      methods can be used to track the binding and movements of individual helicase
      complexes, and allow new insights into helicase behaviors at the single-molecule
      level.

PMID- 29458769
TI  - Single-Molecule Analysis of Replication Protein A-DNA Interactions.
AB  - Replication protein A (RPA) is a highly conserved, eukaryotic ssDNA-binding
      protein essential for genome stability. RPA interacts with ssDNA and with protein
      partners to coordinate DNA replication, repair, and recombination. Single
      molecule analysis of RPA-DNA interactions is leading to a better understanding of
      the molecular interactions and dynamics responsible for RPA function in cells.
      Here, we first describe how to express, purify, and label RPA. We then describe
      how to prepare materials and carry out single-molecule experiments examining RPA
      DNA interactions using total internal reflection fluorescence microscopy (TIRFM).
      Finally, the last section describes how to analyze TIRFM data. This chapter will
      focus on human RPA. However, these methods can be applied to RPA homologs from
      other species.

PMID- 29458770
TI  - Single-Molecule Studies of ssDNA-Binding Proteins Exchange.
AB  - Single-stranded DNA-binding protein (SSB) is important not only for the
      protection of single-stranded DNA (ssDNA) but also for the recruitment of other
      proteins for DNA replication, recombination, and repair. The interaction of SSB
      with ssDNA is highly dynamic as it exists as an intermediate during cellular
      processes that unwind dsDNA. It has been proposed that SSB redistributes itself
      among multiple ssDNA segments, but transient intermediates are difficult to
      observe in bulk experiments. We can use single-molecule FRET microscopy to
      observe intermediates of the transfer of a single Escherichia coli SSB from one
      ssDNA strand to another or exchange of one SSB for another on a single ssDNA in
      real time. This single-molecule approach can be further applicable to understand
      relative binding affinities and competitive dynamics for other SSBs and variants
      across various systems.

PMID- 29458771
TI  - Dissecting the Recombination Mediator Activity of BRCA2 Using Biochemical
      Methods.
AB  - Homologous recombination (HR) is an essential pathway to restart stalled
      replication forks, repair spontaneous DNA double-strand breaks, and generate
      genetic diversity. Together with genetic studies in model organisms, the
      development of purification protocols and biochemical assays has allowed
      investigators to begin to understand how the complex machinery of HR functions.
      At the core of the HR process is the recombination enzyme RecA in bacteria or
      RAD51 and DMC1 in eukaryotes. The main steps of HR can be reconstituted in vitro
      and involve: (1) The formation of a ssDNA-RAD51 complex into a helical structure
      termed the nucleoprotein filament after one DNA strand has been resected at the
      site of the break. (2) The homologous DNA pairing with an intact copy of the
      damaged chromatid to form a joint molecule also called displacement loop (D
      loop). (3) The exchange of DNA strands and de novo DNA synthesis to restore the
      damaged/lost DNA. (4) The resolution of joint molecules by nucleolytic cleavage.
      The human tumor suppressor BRCA2 is a mediator of HR as it actively facilitates
      the DNA transactions of the recombination proteins RAD51 and DMC1 in a variety of
      ways: It stabilizes ssDNA-RAD51/DMC1 nucleoprotein filaments. It limits the
      assembly of RAD51 on dsDNA. It facilitates the replacement of replication protein
      A by RAD51. The result of these activities is a net increase of DNA strand
      exchange products as observed in vitro. Here, we describe some of the biochemical
      assays used to dissect the mediator activities of BRCA2.

PMID- 29458772
TI  - Approaches to Understanding the Mediator Function of Brh2 in Ustilago maydis.
AB  - Primary components of the homologous recombination pathway in eukaryotes include
      Rad51 whose function is to search for DNA sequence homology and promote strand
      exchange, its mediator BRCA2, and Dss1, a key regulator of BRCA2. We seek to
      understand the role of BRCA2 in governing the activity of Rad51 and to learn how
      BRCA2 function is regulated by Dss1. We use the microbe Ustilago maydis as a
      model system for experimentation because it has a well-conserved BRCA2-homolog,
      Brh2, and is amenable to biochemical and molecular genetic manipulations and
      analysis. The powerful attributes of this system open the way for gaining insight
      into BRCA2's molecular mechanism through avenues not immediately approachable in
      the vertebrate systems. Here we provide protocols for preparing Brh2, Dss1, and
      Rad51 as reagents for use in biochemical assays to monitor function and present
      methods for transposon-based mutational analysis of Brh2 for use in genetic
      dissection of function.

PMID- 29458773
TI  - GEN1 Endonuclease: Purification and Nuclease Assays.
AB  - Successful chromosome segregation depends on the timely removal of DNA
      recombination and replication intermediates that interlink sister chromatids.
      These intermediates are acted upon by structure-selective endonucleases that
      promote incisions close to the junction point. GEN1, a member of the Rad2/XPG
      endonuclease family, was identified on the basis of its ability to cleave
      Holliday junction recombination intermediates. Resolution occurs by a nick and
      counter-nick mechanism in strands that are symmetrically related across the
      junction point, leading to the formation of ligatable nicked duplex products. The
      actions of GEN1 are, however, not restricted to HJs, as 5'-flaps and replication
      fork structures also serve as excellent in vitro substrates for the nuclease. In
      the cellular context, GEN1 activity is observed late in the cell cycle, as most
      of the protein is excluded from the nucleus, such that it gains access to DNA
      intermediates after the breakdown of nuclear envelope. Nuclear exclusion ensures
      the protection of replication forks and other DNA secondary structures important
      for normal metabolic processes. In this chapter, we describe the purification of
      recombinant GEN1 and detail biochemical assays involving the use of synthetic DNA
      substrates and cruciform-containing plasmids.

PMID- 29458774
TI  - Biochemical and Structural Properties of Fungal Holliday Junction-Resolving
      Enzymes.
AB  - Four-way Holliday junctions in DNA are the central intermediates of genetic
      recombination and must be processed into regular duplex species. One mechanism
      for achieving this is called resolution, brought about by structure-selective
      nucleases. GEN1 is an important junction-resolving enzyme in eukaryotic cells, a
      member of the FEN1/EXO1 superfamily of nucleases. While human GEN1 is difficult
      to work with because of aggregation, orthologs from thermophilic fungi have been
      identified using bioinformatics and have proved to have excellent properties.
      Here, the expression and purification of this enzyme from Chaetomium thermophilum
      is described, together with the means of investigating its biochemical
      properties. The enzyme is quite similar to junction-resolving enzymes from lower
      organisms, binding to junctions in dimeric form, introducing symmetrical
      bilateral cleavages, the second of which is accelerated to promote productive
      resolution. Crystallization of C. thermophilum GEN1 is described, and the
      structure of a DNA-product complex. Juxtaposition of complexes in the crystal
      lattice suggests how the structure of a dimeric enzyme with an intact junction is
      organized.

PMID- 29458775
TI  - Preparation and Resolution of Holliday Junction DNA Recombination Intermediates.
AB  - Holliday junctions provide a covalent link between recombining DNA molecules and
      need to be removed prior to chromosome segregation at mitosis. Defects in their
      resolution lead to mitotic catastrophe, characterized by the formation of DNA
      breaks and chromosome aberrations. Enzymes that resolve recombination
      intermediates have been identified in all forms of life, from bacteriophage, to
      bacteria, yeast, and humans. In higher eukaryotes, Holliday junctions are
      resolved by GEN1, a nuclease that is mechanistically similar to the prototypic
      resolvase Escherichia coli RuvC, and by the SMX trinuclease complex. Studies of
      these enzymes have been facilitated by the use of plasmid-sized DNA recombination
      intermediates made by RecA-mediated strand exchange. Here, we detail the
      preparation of these recombination intermediates, which resemble alpha
      structures, and their resolution by RuvC and GEN1.

PMID- 29458777
TI  - Preface.

PMID- 29458776
TI  - Methods to Study DNA End Resection II: Biochemical Reconstitution Assays.
AB  - DNA end resection initiates the largely accurate repair of DNA double-strand
      breaks (DSBs) by homologous recombination. Specifically, recombination requires
      the formation of 3' overhangs at DSB sites, which is carried out by nucleases
      that specifically degrade 5'-terminated DNA. In most cases, DNA end resection is
      a two-step process, comprising of initial short-range followed by more processive
      long-range resection. In this chapter, we describe selected assays that
      reconstitute both the short- and long-range pathways. First, we define methods to
      study the exonuclease and endonuclease activities of the MRE11-RAD50-NBS1 (MRN)
      complex in conjunction with phosphorylated cofactor CtIP. This reaction is
      particularly important to initiate processing of DNA breaks and to recruit
      components belonging to the subsequent long-range pathway. Next, we describe
      assays that reconstitute the concerted reactions of Bloom (BLM) or Werner (WRN)
      helicases that function together with the DNA2 nuclease-helicase, and which are
      as a complex capable to resect DNA of kilobases in length. The reconstituted
      reactions allow us to understand how the resection pathways function at the
      molecular level. The assays will be invaluable to define regulatory mechanisms
      and to identify inhibitory compounds, which may be valuable in cancer therapy.

PMID- 29458778
TI  - Anti-hypertensive drugs and skin cancer risk: a review of the literature and meta
      analysis.
AB  - INTRODUCTION: Several anti-hypertensive drugs have photosensitizing properties,
      however it remains unclear whether long-term users of these drugs are also at
      increased risk of skin malignancies. We conducted a literature review and meta
      analysis on the association between use of anti-hypertensive drugs and the risk
      of cutaneous melanoma and non-melanoma skin cancer (NMSC). METHODS: We searched
      PubMed, EMBASE, Google Scholar and the Cochrane Library, and included
      observational and experimental epidemiological studies published until February
      28th, 2017. We calculated summary relative risk (SRR) and 95% confidence
      intervals (95% CI) through random effect models to estimate the risk of skin
      malignancies among users of the following classes of anti-hypertensive drugs:
      thiazide diuretics, angiotensin converting enzyme inhibitors (ACEi), angiotensin
      receptor blockers (ARB), calcium channel blockers (CCB) and beta-blockers. We
      conducted sub-group and sensitivity analysis to explore causes of between-studies
      heterogeneity, and assessed publication bias using a funnel-plot based approach.
      RESULTS: Nineteen independent studies were included in the meta-analysis. CCB
      users were at increased skin cancer risk (SRR 1.14, 95% CI 1.07-1.21), and beta
      blockers users were at increased risk of developing cutaneous melanoma (SRR 1.21,
      95% CI 1.05-1.40), with acceptable between-studies heterogeneity (I2 < 50%).
      There was no association between thiazide diuretics, ACEi or ARB use and skin
      cancer risk. We found no evidence of publication bias affecting the results.
      CONCLUSION: Family doctors and clinicians should inform their patients about the
      increased risk of skin cancer associated with the use of CCB and beta-blockers
      and instruct them to perform periodic skin self-examination. Further studies are
      warranted to elucidate the observed associations.

PMID- 29458779
TI  - Systemic treatment in adult uterine sarcomas.
AB  - Uterine sarcomas (US) are rare mesenchymal tumours of the uterus and are divided
      mainly into uterine leiomyosarcoma (uLMS), low grade endometrial stromal sarcoma
      (LG-ESS), high grade endometrial stromal sarcoma (HG-ESS), adenosarcomas and high
      grade undifferentiated sarcoma (HGUS). US are often high-grade tumours with a
      high local recurrence rate and metastatic risk. We here discuss the current
      standard of care and knowledge of systemic therapy for adult uterine sarcomas, in
      particular uLMS, LG-ESS, HG-ESS and HGUS, in both the adjuvant as well as the
      metastatic setting.

PMID- 29458780
TI  - Immune dysregulation in myelodysplastic syndrome: Clinical features, pathogenesis
      and therapeutic strategies.
AB  - Myelodysplastic syndrome (MDS) is a heterogeneous hematological malignancy,
      characterized by cytopenia and accompanied by a risk of transformation into acute
      myeloid leukemia (AML). Epidemiological studies for decades have shown
      association between autoimmune diseases (AIDs) and MDS. Specifically, patients
      with antecedent AIDs tends to have an increased risk of developing MDS, and these
      patients display different clinical characteristics and outcomes. Importantly,
      immune dysregulation has been the common driving force between MDS and AIDs
      pathogenesis. Both innate and adaptive immune systems are overly active in the
      hematopoietic niche of MDS. It has been observed that in addition to many
      cytokines secreted in the bone marrow (BM) microenvironment, almost all types of
      immune cells and their downstream signaling pathways participate in MDS
      pathogenesis and evolution. Currently, growth factor therapy and hypomethylating
      agents (HMAs), along with supportive care, are the mainstay for MDS treatment. As
      information about the contribution of immune system has started emerging in
      different subtypes of MDS, we need to highlight the value of immunomodulatory
      therapies. Immune activation seems to participate specifically in the development
      of lower-risk MDS, and therefore, use of immunosuppressive therapies would be an
      ideal treatment option for this type. However, in high-risk MDS, escape from
      immune surveillance appears to contribute to its progression, and thus, several
      immune-activating treatment options, including immune checkpoint inhibitors and
      vaccines, are being considered. HMAs have been approved for use in treating high
      risk MDS for many years based on their cytotoxicity, but since they also display
      an epigenetic-immunomodulatory role, they can be an option for lower-risk MDS.
      Thus, in this review, we discuss the immune dysregulation in MDS, including its
      clinical features, pathogenic mechanism and immunomodulatory therapeutic options.

PMID- 29458781
TI  - Melatonin and breast cancer: Evidences from preclinical and human studies.
AB  - The breast cancer affects women with high mortality and morbidity worldwide. The
      risk is highest in the most developed world but also is markedly rising in the
      developing countries. It is well documented that melatonin has a significant anti
      tumor activities demonstrated on various cancer types in a plethora of
      preclinical studies. In breast cancer, melatonin is capable to disrupt estrogen
      dependent cell signaling, resulting in a reduction of estrogen-stimulated cells,
      moreover, it's obvious neuro-immunomodulatory effect in organism was described.
      Several prospective studies have demonstrated the inverse correlation between
      melatonin metabolites and the risk of breast cancer. This correlation was
      confirmed by observational studies that found lower melatonin levels in breast
      cancer patients. Moreover, clinical studies have showed that circadian disruption
      of melatonin synthesis, specifically night shift work, is linked to increased
      breast cancer risk. In this regard, proper light/dark exposure with more
      selective use of light at night along with oral supplementation of melatonin may
      have benefits for high-risk women. The results of current preclinical studies,
      the mechanism of action, and clinical efficacy of melatonin in breast cancer are
      reviewed in this paper. Melatonin alone or in combined administration seems to be
      appropriate drug for the treatment of early stages of breast cancer with
      documented low toxicity over a wide range of doses. These and other issues are
      also discussed.

PMID- 29458782
TI  - Loco-regional treatment for castration-resistant prostate cancer: Is there any
      rationale? A critical review from the AFU-GETUG.
AB  - Emerging evidence from population-based and retrospective series suggests a
      potential improvement of clinical outcomes in metastatic prostate cancer.
      Moreover, metastasis-directed treatment has shown encouraging results in this
      setting. There is an increasing interest in exploring the potential of local
      therapies in advanced prostate cancer, but this has rarely been specifically
      addressed in the castration-resistant state, whether non-metastatic or
      metastatic. A review of relevant articles was performed on the oncologic benefit
      of local treatment of the primary tumor or metastasis-targeted treatment in
      castration-resistant prostate cancer patients. The main goal of this strategy is
      to delay introduction of a new systemic agent to maintain quality of life and
      potentially to limit resistance. Further investigation is required to provide
      high-level evidence for the oncologic benefit of this treatment modality.

PMID- 29458783
TI  - Precision medicine in ALK rearranged NSCLC: A rapidly evolving scenario.
AB  - IMPORTANCE: The identification of anaplastic lymphoma kinase (ALK) rearrangements
      in 2-5% of non-small cell lung cancer (NSCLC) patients led to the rapid clinical
      development of its oral tyrosine kinase inhibitor (TKI). Crizotinib was the first
      ALK inhibitor approved and utilised in the treatment of ALK+ NSCLC patients in
      the second line setting first and subsequently in the first line one. Since then
      many other ALK inhibitors have been developed (ceritinib, alectinib, brigatinib,
      lorlatinib,etc) and the treatment paradigm of these patients has considerably
      drifted. The questions regarding their treatment at progression remains
      unanswered at the moment. OBJECTIVE: Our review clarifies what it is the state of
      the art in the treatment of ALK rearranged NSCLC patients, highlights the
      mechanisms of primary and secondary resistance mutations and suggests a treatment
      algorithm based on specific primary resistance or acquired mutations. EVIDENCE
      REVIEW: Studies that enrolled ALK+ NSCLC patients with locally advance or
      metastatic disease receiving treatment with ALK inhibitor, first or second line,
      were identified using electronic databases (MEDLINE, EMBASE, and Cochrane
      library). Trials were excluded if they were phase 1, enrolled less than 10
      patients. FINDING: Overall 1942 patients were included in our review. It confirms
      the role and the efficacy in first line of Alectinib but it highlights also that
      all the ALK inhibitors could play a crucial role during the patients' journey.
      Identifying the different mutations and utilising the most active ALK inhibitor
      depending on the "up-to-date" driven mutation is the way forward in the
      management of those patients. CONCLUSIONS AND RELEVANCE: the review shows the
      rapid drifting in the management of ALK+ NSCLC patients and the importance of
      fully understanding and acknowledging the role of the resistance mutation,
      primary or acquired. We strongly advocate a comprehensive genomic approach in the
      management of ALK+ NSCLC patients who develop resistance mutations that are still
      targetable by a different ALK inhibitor.

PMID- 29458784
TI  - Review: Effectiveness of implementation strategies to increase physical activity
      uptake during and after cancer treatment.
AB  - BACKGROUND: The purpose of this review was to assess the effectiveness of
      different strategies to implement physical activity during and after cancer
      treatment. DESIGN: We searched for studies containing strategies to implement
      physical activity in cancer care that meet the inclusion criteria of the Cochrane
      EPOC group. The primary outcome was physical activity uptake. We expressed the
      effectiveness of the strategies as the percentage of studies with improvement.
      RESULTS: Nine studies met the inclusion criteria. Patient groups doing physical
      activities via an implementation strategy had better outcomes than those
      receiving usual care: 83% of the studies showed improvement. Strategies showing
      significant improvement compared to usual care employed healthcare professionals
      to provide individual counselling or advice for exercise or interactive elements
      such as audit and feedback systems. When comparing the different strategies 1)
      interactive elements or 2) elements tailored to the needs of the patients had
      better physical activity uptake. CONCLUSIONS: Implementation strategies
      containing individual and interactive elements, tailored to the individual needs
      of patients, are more successful in improving physical activity uptake.

PMID- 29458785
TI  - ECCO essential requirements for quality cancer care: Melanoma.
AB  - BACKGROUND: ECCO essential requirements for quality cancer care (ERQCC) are
      explanations and descriptions of challenges, organisation and actions that are
      necessary to give high-quality care to patients who have a specific type of
      cancer. They are written by European experts representing all disciplines
      involved in cancer care. ERQCC papers give oncology teams, patients, policymakers
      and managers an overview of the elements needed in any healthcare system to
      provide high quality of care throughout the patient journey. References are made
      to clinical guidelines and other resources where appropriate, and the focus is on
      care in Europe. MELANOMA: ESSENTIAL REQUIREMENTS FOR QUALITY CARE: CONCLUSION:
      Taken together, the information presented in this paper provides a comprehensive
      description of the essential requirements for establishing a high-quality service
      for melanoma. The ERQCC expert group is aware that it is not possible to propose
      a 'one size fits all' system for all countries, but urges that access to
      multidisciplinary teams and specialised treatments is guaranteed to all patients
      with melanoma.

PMID- 29458786
TI  - ECCO essential requirements for quality cancer care: Oesophageal and gastric
      cancer.
AB  - BACKGROUND: ECCO essential requirements for quality cancer care (ERQCC) are
      checklists and explanations of organisation and actions that are necessary to
      give high-quality care to patients who have a specific type of cancer. They are
      written by European experts representing all disciplines involved in cancer care.
      ERQCC papers give oncology teams, patients, policymakers and managers an overview
      of the elements needed in any healthcare system to provide high quality of care
      throughout the patient journey. References are made to clinical guidelines and
      other resources where appropriate, and the focus is on care in Europe.
      OESOPHAGEAL AND GASTRIC: ESSENTIAL REQUIREMENTS FOR QUALITY CARE: CONCLUSION:
      Taken together, the information presented in this paper provides a comprehensive
      description of the essential requirements for establishing a high-quality OG
      cancer service. The ERQCC expert group is aware that it is not possible to
      propose a 'one size fits all' system for all countries, but urges that access to
      multidisciplinary units or centres must be guaranteed for all those with OG
      cancer.

PMID- 29458787
TI  - A systematic review of the safety profile of the different combinations of
      fluoropyrimidines and oxaliplatin in the treatment of colorectal cancer patients.
AB  - The available fluoropyrimidines and oxaliplatin combinations for colorectal
      cancer patients have different safety profiles. The aim of this systematic review
      was to compare their toxicities. The eligible studies were classified as: no
      bolus; 5-FU single bolus; 5-FU double bolus; capecitabine. We calculated the
      incidence of "any-grade" and "severe" toxicity for haematological and non
      haematological adverse events of each group. We identified 184 treatment groups;
      compared to 5-FU double bolus, except for high-grade anaemia, all the groups
      showed reduced risk of haematological toxicities, with the most relevant
      advantages for single bolus regimens. Concerning non-haematological toxicities,
      compared to double bolus, the single bolus group showed a statistically
      significant reduced risk for many gastrointestinal toxicities and for pheripheral
      neuropathy. This is the first systematic review of the toxicity profile of
      different 5-FU or capecitabine and oxaliplatin regimens. Single 5-FU bolus is
      associated with a definitely favourable toxicity profile, both for haematological
      and non-haematological toxicity.

PMID- 29458788
TI  - Protective effects of curcumin against doxorubicin-induced toxicity and
      resistance: A review.
AB  - Doxorubicin (DOX)-induced toxicity and resistance are major obstacles in
      chemotherapeutic approaches. Despite effective in the treatment of numerous
      malignancies, some clinicians have voiced concern that DOX has the potential to
      cause debilitating consequences in organ tissues, especially the heart. The
      mechanisms of toxicity and resistance are respectively related to induction of
      reactive oxygen species (ROS) and up-regulation of ATP-binding cassette (ABC)
      transporter. Curcumin (CUR) with several biological and pharmacological
      properties is expected to restore DOX-mediated impairments to tissues. This
      review is intended to address the current knowledge on DOX adverse effects and
      CUR protective actions in the heart, kidneys, liver, brain, and reproductive
      organs. Coadministration of CUR and DOX is capable of ameliorating DOX toxicity
      pertained to antioxidant, apoptosis, autophagy, and mitochondrial permeability.

PMID- 29458789
TI  - Physical activity reduces fatigue in patients with cancer and hematopoietic stem
      cell transplant recipients: A systematic review and meta-analysis of randomized
      trials.
AB  - PURPOSE: Objective was to determine whether physical activity reduces the
      severity of fatigue in patients with cancer or hematopoietic stem cell transplant
      (HSCT) recipients. METHODS: We conducted a meta-analysis of randomized trials
      comparing physical activity with control interventions for the management of
      fatigue in patients with cancer or HSCT recipients. RESULTS: There were 170
      trials included. Physical activity reduced the severity of fatigue when compared
      to all control groups (standardized mean difference -0.49, 95% confidence
      interval -0.60 to -0.37; P < 0.00001). Aerobic, neuromotor, resistance and
      combination exercises were all effective in reducing fatigue although smaller
      effects were observed with resistance exercises (P interaction = 0.01). Other
      intervention and patient characteristics did not influence the effect of physical
      activity on the severity of fatigue. CONCLUSIONS: Physical activity was effective
      at reducing fatigue in patients with cancer and HSCT recipients across patient
      sub-groups. Determining the best approaches for safe implementation should be a
      priority.

PMID- 29458790
TI  - Non pharmacological interventions and non-fentanyl pharmacological treatments for
      breakthrough cancer pain: A systematic and critical review.
AB  - BACKGROUND: Oral opioids or other pharmacological or non-pharmacological
      interventions are often suggested in the management of breakthrough cancer pain
      (BTcP). The aim of this systematic and critical review was to analyse and
      critically comment the evidence of any non-fentanyl therapies proposed for BTcP.
      METHODS: A systematic literature search was carried out to find studies providing
      clinical data on any treatment excluding fentanyl products. RESULTS: No data
      exist about the use of oral opioids. Some information is available on parenteral
      morphine in a large sample of patients and episodes of BTcP. For other
      treatments, including methadone, nitrous oxide, anti-inflammatory drugs,
      samarium, and gabapentin the existing data, observational and obtained in a small
      number of patients do not provide useful information to be generalized. Only
      ketamine, a drug difficult to use for many physicians, particularly in determined
      setting, provided some evidence according a randomized controlled double-blind
      study. CONCLUSIONS: Recommendations suggesting the use of oral opioids or other
      pharmacological and non-pharmacologic interventions for BTcP, are not based on
      any, even minimal evidence. These treatments are worthwhile of further
      investigation, particularly in determined conditions that should fit the
      pharmacokinetics of oral opioids.

PMID- 29458791
TI  - The ethical plausibility of the 'Right To Try' laws.
AB  - 'Right To Try' (RTT) laws originated in the USA to allow terminally ill patients
      to request access to early stage experimental medical products directly from the
      producer, removing the oversight and approval of the Food and Drug
      Administration. These laws have received significant media attention and almost
      equally unanimous criticism by the bioethics, clinical and scientific
      communities. They touch indeed on complex issues such as the conflict between
      individual and public interest, and the public understanding of medical research
      and its regulation. The increased awareness around RTT laws means that healthcare
      providers directly involved in the management of patients with life-threatening
      conditions such as cancer, infective, or neurologic conditions will deal more
      frequently with patients' requests of access to experimental medical products.
      This paper aims to assess the ethical plausibility of the RTT laws, and to
      suggest some possible ethical tools and considerations to address the main issues
      they touch.

PMID- 29458792
TI  - Circulating tumour DNA, a promising biomarker for the management of colorectal
      cancer.
AB  - Circulating cell free tumour DNA (ctDNA) maintains the same genomic alterations
      that are present in the corresponding tumour, thereby allowing for quantitative
      and qualitative real-time evaluation in body fluids as an alternative to onerous
      repeat biopsies. Improvements in the sensitivity of techniques used to identify
      ctDNA has led to a surge of research investigating its role in the detection of:
      early disease, relapse, response to therapy and emerging drug resistance
      mechanisms. Following curative surgery, ctDNA detection is a promising marker of
      minimal residual disease and could better select patients for adjuvant
      chemotherapy. Longitudinal monitoring could help identify early relapse. In
      metastatic disease, ctDNA can predict response to chemotherapy prior to evidence
      of disease progression on imaging and investigate novel primary and acquired
      resistance mechanisms to targeted therapies. More experience in detecting,
      analysing and interpreting ctDNA within prospective trials, will better define
      its role for implementation into routine clinical practice.

PMID- 29458793
TI  - An attempt to conceptualize the individual onco-functional balance: Why a
      standardized treatment is an illusion for diffuse low-grade glioma patients.
AB  - In the era of evidence-based medicine, clinicians aim to establish standards of
      care from randomized studies. Following, personalized medicine has emerged, as
      new individualized biomarkers could help to predict sensitivity to specific
      treatment. In this paper, we show that, for diffuse low-grade glioma, some
      specificities - dual goal of both survival and functional gain, long duration of
      the disease with multistep treatments, multiparametric evaluation of the onco
      functional balance of each treatment modality - call for a change of paradigm.
      After summarizing how to weight the benefits and risks of surgery, chemotherapy
      and radiotherapy, we show that the overall efficacy of a treatment modality
      cannot be assessed per se, as it depends on its integration in the whole
      sequence. Then, we revisit the notion of personalized medicine: instead of
      decision-making based solely on molecular profile, we plead for a recursive
      algorithm, allowing a dynamic evaluation of the onco-functional balance,
      integrating many individual characteristics of the patient's tumor and brain
      function.

PMID- 29458794
TI  - The role of human papillomavirus vaccines in cervical cancer: Prevention and
      treatment.
AB  - Human papillomavirus (HPV) is the most common sexually transmitted disease,
      worldwide. Primary prevention thorough vaccination si able to reduce the burden
      of HPV-related lesions. Ten years ago the Food and drug Administration (FDA)
      approved the first vaccine against HPV. In the last decades, growing data on
      safety and effectiveness have been collected. In the present review we report the
      current knowledge on vaccine against HPV, highlighting the current value and
      prospective regarding the widespread diffusion of HPV vaccines. The role of
      emerging therapeutic vaccines is reviewed.

PMID- 29458795
TI  - Mucins: Structural diversity, biosynthesis, its role in pathogenesis and as
      possible therapeutic targets.
AB  - Mucins are the main structural components of mucus that create a selective
      protective barrier for epithelial surface and also execute wide range of other
      physiological functions. Mucins can be classified into two types, namely secreted
      mucins and membrane bounded mucins. Alterations in mucin expression or
      glycosylation and mislocalization have been seen in various types of pathological
      conditions such as cancers, inflammatory bowel disease and ocular disease, which
      highlight the importance of mucin in maintaining homeostasis. Hence mucins can be
      used as attractive target for therapeutic intervention. In this review, we
      discuss in detail about the structural diversity of mucins; their biosynthesis;
      its role in pathogenesis; regulation and as possible therapeutic targets.

PMID- 29458796
TI  - Beware the Danger Lurking Under the Shroud of Alcohol.

PMID- 29458797
TI  - Man With Rash.

PMID- 29458798
TI  - Child With Diffuse Bullous Rash.

PMID- 29458802
TI  - What Role Has Emergency Medicine Played in the Opioid Epidemic: Partner in Crime
      or Canary in the Coal Mine?: March 2018 Annals of Emergency Medicine Journal
      Club.

PMID- 29458799
TI  - Rocuronium Versus Succinylcholine Revisited: Succinylcholine Remains the Best
      Choice.

PMID- 29458803
TI  - Correction.

PMID- 29458804
TI  - Adult Male With Chest Pain After a Fall.

PMID- 29458805
TI  - Man With Abdominal Pain.

PMID- 29458806
TI  - Elderly Woman With Abdominal Pain.

PMID- 29458807
TI  - Managers Are Necessary; Leaders Are Essential.

PMID- 29458808
TI  - Bougie Use and First-Pass Intubation Success in the Emergency Department.

PMID- 29458809
TI  - In reply.

PMID- 29458810
TI  - In reply.

PMID- 29458811
TI  - Planning for Future Disasters: Telemedicine as a Resource.

PMID- 29458812
TI  - Young Boy With Roughening in the Inner Eyelids.

PMID- 29458813
TI  - Mechanical Ventilation.

PMID- 29458815
TI  - Clinical Emergency Data Registry Quality Measures.

PMID- 29458816
TI  - Distracted and Impaired Driving.

PMID- 29458814
TI  - Pediatric Medication Safety in the Emergency Department.

PMID- 29458817
TI  - Hospital Disaster Physician Privileging.

PMID- 29458818
TI  - Medical Transport Advertising, Marketing, and Brokering.

PMID- 29458819
TI  - State Medical Board Peer Review.

PMID- 29458820
TI  - Subdissociative-Dose Ketamine for Analgesia.

PMID- 29458821
TI  - The Clinical Practice of Emergency Medical Services Medicine.

PMID- 29458822
TI  - The Role of the Physician Medical Director in Emergency Medical Services
      Leadership.

PMID- 29458823
TI  - Unsolicited Medical Personnel Volunteering at Disaster Scenes.

PMID- 29458824
TI  - Writing Admission and Transition Orders.

PMID- 29458825
TI  - Workforce Diversity in Health Care Settings.

PMID- 29458826
TI  - Using Local Therapy to Control Noninfectious Uveitis.

PMID- 29458827
TI  - Fibrin Web in a Patient with Candida glabrata Endophthalmitis.

PMID- 29458828
TI  - West African Crystalline Maculopathy in a Nigerian Woman.

PMID- 29458830
TI  - Corrigendum.

PMID- 29458829
TI  - Unilateral Double Optic Nerve Head Pits.

PMID- 29458831
TI  - Corrigendum.

PMID- 29458832
TI  - Re: Shantha et al.: Ophthalmic manifestations and causes of vision impairment in
      Ebola virus disease survivors in Monrovia, Liberia (Ophthalmology. 2017;124:170
      177).

PMID- 29458833
TI  - Reply.

PMID- 29458834
TI  - Re: Pazos et al.: Diagnostic accuracy of Spectralis SD OCT automated macular
      layers segmentation to discriminate normal from early glaucomatous eyes
      (Ophthalmology. 2017;124:1218-1228).

PMID- 29458835
TI  - Reply.

PMID- 29458836
TI  - Re: Akagi et al.: Rates of local retinal nerve fiber layer thinning before and
      after disc hemorrhage in glaucoma (Ophthalmology. 2017;124:1403-1411).

PMID- 29458837
TI  - Reply.

PMID- 29458838
TI  - Re: Chang et al.: Accuracy of diagnostic imaging modalities for classifying
      pediatric eyes as papilledema versus pseudopapilledema (Ophthalmology.
      2017;124:1839-1848).

PMID- 29458839
TI  - Reply.

PMID- 29458840
TI  - Genome-wide circulating microRNA expression profiling reveals potential
      biomarkers for amyotrophic lateral sclerosis.
AB  - The occurrence of mutations of TDP-43, FUS, and C9ORF72 in amyotrophic lateral
      sclerosis (ALS) suggests pathogenic alterations to RNA metabolism and
      specifically to microRNA (miRNA) biology. Moreover, several ALS-related proteins
      impact stress granule dynamics affecting miRNA biogenesis and cellular miRNA
      levels. miRNAs are present in different biological fluids and have been proposed
      as potential biomarkers. Here we used next-generation sequencing to perform a
      comparative analysis of the expression profile of circulating miRNAs in the serum
      of 2 mutant superoxide dismutase 1 transgenic mice. Top hit candidates were then
      validated using quantitative real-time polymerase chain reaction, confirming
      significant changes for 6 miRNAs. In addition, one of these miRNAs was also
      altered in mutant TDP-43 mice. Then, we tested this set of miRNAs in the serum
      from sporadic ALS patients, observing a significant deregulation of hsa-miR-142
      3p and hsa-miR-1249-3p. A negative correlation between the revised ALS functional
      rating scale and hsa-miR-142-3p levels was found. Bioinformatics analysis of the
      regulatory network governed by hsa-miR-142-3p identified TDP-43 and C9orf72 as
      possible targets, suggesting a connection with ALS pathogenesis. This study
      identifies miRNAs that are altered in ALS that may serve as potentials
      biomarkers.

PMID- 29458841
TI  - Early-life stress induces cognitive disorder in middle-aged mice.
AB  - Early-life stress can induce several neuropsychological disorders in adulthood.
      However, the underlying mechanisms inducing such disorders are still not fully
      understood. Furthermore, the effects of early-life stress on the changes in
      cognitive function with age are still not clarified. In this study, we used
      maternal deprivation (MD) to examine the cognitive function in middle-aged mice
      using a touchscreen-equipped operant chamber. In the visual-discrimination task,
      the aged (~1.4 years old) control mice could accurately learn to discriminate
      between different visual stimuli. In contrast, the correct response rate of aged
      MD mice increased to ~60% by day 10; it was still significantly lower than that
      of the control mice (85%). In the hippocampus of aged MD mice, the expression
      level of the N-methyl-d-aspartate receptor subunit GluN1 decreased significantly
      as compared to that in control mice. On the other hand, no significant difference
      in GluN1 expression level was detected in young (2.5 months old) mice. These
      findings indicate that early-life stress accelerates cognitive impairment in
      middle-aged mice.

PMID- 29458843
TI  - A critical role for very long-chain fatty acid elongases in oleic acid-mediated
      Saccharomyces cerevisiae cytotoxicity.
AB  - Elongases FEN1/ELO2 and SUR4/ELO3 are important enzymes involved in the
      elongation of long-chain fatty acids (LCFAs) to very long-chain fatty acids
      (VLCFAs) in Saccharomyces cerevisiae. The molecular mechanism of the involvement
      of these elongases in lipotoxicity is unclear. In the present study, we
      investigated the role of VLCFA elongases in oleic acid-mediated yeast
      cytotoxicity. The spot test showed that yeast strains with the deletion of ELO2
      or ELO3 were strikingly sensitive to oleic acid, while there was no change on the
      growth of strain with deleted ELO1 which was involved in the elongation of C14
      fatty acid (FA) to C16 FA. By using GC-MS, the unsaturation index was increased
      in elo2? and elo3? mutants after treatment with oleic acid (OLA). However, the
      proportion of VLCFAs was increased in response to OLA in the wild-type strain.
      The growth inhibition of elo2? and elo3? could be partially rescued by two
      commonly used antioxidant agents N-acetyl cysteine (NAC) and Ascorbic acid (VC).
      The further study showed that exposure to excess OLA led to an increase in the
      levels of reactive oxygen species (ROS) and thiobarbituric acid reactive
      substances (TBARS), and a decline in the quantity of reduced glutathione (GSH) in
      both the wild type and mutant strains. However, the antioxidant enzyme activities
      of superoxide dismutase (SOD) and catalase (CAT) were increased in the wild type
      and elo1? strains, while they were significantly decreased in the mutants of
      elo2? and elo3? after treated with excess OLA. Thus, oxidative damage mainly
      contributed to the cell death induced by OLA in ole2? and ole3?. Taken together,
      although disruption of ELO2 or ELO3 did not affect the cellular lipid
      unsaturation, they altered the distribution and propotion of cellular VLCFAs,
      leading to the cell membrane impairment, which augmented the ability of OLA to
      permeabilize the plasma membrane. The data suggest that the very long-chain fatty
      acids elongases ELO2 and ELO3 play important roles in lipotoxic cell death
      induced by OLA through maintaining a balanced FA composition in plasma membrane.

PMID- 29458842
TI  - Cognitive response to fish oil, blueberry, and combined supplementation in older
      adults with subjective cognitive impairment.
AB  - Given evidence that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and
      anthocyanin-rich blueberries provide neurocognitive benefit, we investigated long
      term supplementation in older adults with cognitive complaints. In a 24-week
      randomized, double-blind, placebo-controlled trial, elderly men and women
      received daily fish oil (FO) or blueberry (BB) or both. Diet records confirmed
      that participants reduced background consumption of EPA, DHA, and anthocyanins as
      prescribed. Erythrocyte EPA + DHA composition increased in the FO groups (p =
      0.0001). Total urinary anthocyanins did not differ between the groups after
      supplementation but glycoside and native (food) forms increased only in the BB
      supplemented groups. The FO (p = 0.03) and BB (p = 0.05) groups reported fewer
      cognitive symptoms, and the BB group showed improved memory discrimination (p =
      0.04), indicating that supplementation improved cognition. Cognitive benefit in
      the BB group was associated with the presence of urinary anthocyanins reflecting
      recent BB intake but not with anthocyanin metabolites. However, combined FO + BB
      treatment was not associated with cognitive enhancement as expected.

PMID- 29458844
TI  - Modulation in phenolic root exudate profile of Abelmoschus esculentus expressing
      activation of defense pathway.
AB  - Phenolics play a key role in communication between plants and microbes in the
      rhizosphere. In this study, shikimic, gallic, fumaric, ferulic, vanillic acid and
      quercetin in root exudates of Abelmoschus esculentus act as chemoattractants of
      endophytic Alcaligenes faecalis strains, BHU 12, BHU 16 and BHU M7. In vitro
      chemotaxis assay showed that BHU 12 expressed highest chemotactic movement (CFU
      ~50*1012) towards A.esculentus root exudates followed by BHU 16 and BHU M7 (CFU~
      9*1012), thereby confirming their ability to colonize the host rhizoplane region.
      However, BHU 16 expressed highest biofilm formation ability followed by BHU 12
      and BHU M7. Assessment of chemotactic and biofilm formation potential towards
      individual phenolic acids revealed BHU 12 to be maximally attracted towards 1MUM
      shikimic acid (2*1015) while BHU 16 towards 1mM vanillic acid (6.5*1012) and BHU
      M7 towards 1mM ferulic acid (3.5*1012), thereby confirming the phenolic acid
      components responsible for particularly attracting the endophytic isolates. Upon
      colonization, the endophytic isolates modified the phenolic profiles of root
      exudates in planta in a manner so as to plausibly attract more of the beneficial
      rhizospheric microbiota as well as self-fortification against pathogenic
      microbes. This hypothesis was verified by monitoring the changes in phenolic
      components of A. esculentus root exudate owing to S. rolfsii infection, a
      disastrous soil-borne pathogen. Thus, on the whole, the work provides intricate
      details of plant-endophyte interactions for biotic stress management through
      careful manipulation of root exudates, thereby aiding in sustainable agriculture.

PMID- 29458845
TI  - Leptospirosis in human: Biomarkers in host immune responses.
AB  - Leptospirosis remains one of the most widespread zoonotic diseases caused by
      spirochetes of the genus Leptospira, which accounts for high morbidity and
      mortality globally. Leptospiral infections are often found in tropical and
      subtropical regions, with people exposed to contaminated environments or animal
      reservoirs are at high risk of getting the infection. Leptospirosis has a wide
      range of clinical manifestations with non-specific signs and symptoms and often
      misdiagnosed with other acute febrile illnesses at early stage of infection.
      Despite being one of the leading causes of zoonotic morbidity worldwide, there is
      still a gap between pathogenesis and human immune responses during leptospiral
      infection. It still remains obscure whether the severity of the infection is
      caused by the pathogenic properties of the Leptospira itself, or it is a
      consequence of imbalance host immune factors. Hence, in this review, we seek to
      summarize the past and present milestone findings on the biomarkers of host
      immune response aspects during human leptospiral infection, including cytokine
      and other immune mediators. A profound understanding of the interlink between
      virulence factors and host immune responses during human leptospirosis is
      imperative to identify potential biomarkers for diagnostic and prognostic
      applications as well as designing novel immunotherapeutic strategies in future.

PMID- 29458847
TI  - The special existences: nanoRNA and nanoRNase.
AB  - To adapt to a wide range of nutritional and environmental changes, cells must
      adjust their gene expression profiles. This process is completed by the frequent
      transcription and rapid degradation of mRNA. mRNA decay is initiated by a series
      of endo- and exoribonucleases. These enzymes leave behind 2- to 5-nt-long
      oligoribonucleotides termed "nanoRNAs" that are degraded by specific nanoRNases;
      the degradation of nanoRNA is essential because nanoRNA can mediate the priming
      of transcription initiation that is harmful for the cell via an unknown
      mechanism. Identified nanoRNases include Orn in E. coli, NrnA and NrnB in B.
      subtilis, and NrnC in Bartonella. Even though these nanoRNases can degrade
      nanoRNA specifically into mononucleotides, the biochemical features, structural
      features and functional mechanisms of these enzymes are different. Sequence
      analysis has identified homologs of these nanoRNases in different bacteria,
      including Gammaproteobacteria, Betaproteobacteria, Alphaproteobacteria,
      Firmicutes and Cyanobacteria. However, there are several bacteria, such as those
      belonging to the class Thermolithobacteria, that do not have homologs of these
      nanoRNases. In this paper, the source of nanoRNA, the features of different kinds
      of nanoRNases and the distribution of these enzymes in prokaryotes are described
      in detail.

PMID- 29458846
TI  - Desert actinobacteria as a source of bioactive compounds production with a
      special emphases on Pyridine-2,5-diacetamide a new pyridine alkaloid produced by
      Streptomyces sp. DA3-7.
AB  - In the present study, 134 morphologically distinct actinobacteria isolates were
      obtained from soil samples from 10 different localities in the Saudi Arabian
      desert. The preliminary screening revealed that 16 of these isolates possessed
      antimicrobial activity. One isolate, which was identified as Streptomyces sp. DA3
      7, possessed broad-spectrum antimicrobial activity against both gram-positive and
      gram-negative bacteria, as well as against fungi, and modified nutrient glucose
      medium was suitable for Streptomyces sp. DA3-7 to produce extracellular
      metabolites. The ethyl acetate extract of Streptomyces sp. DA3-7 exhibited
      antimicrobial activity against Enterococcus faecalis and Salmonella typhimurium,
      with minimum inhibitory concentrations of 78 and 156MUg/mL, respectively, as well
      as strong cytotoxicity (24h IC50 85MUg/mL) against MCF-7 human breast
      adenocarcinoma cells. The active compound was separated, purified, and identified
      as Pyridine-2,5-diacetamide (C9H11N3O2+H+, 194.21), which possessed a lowest
      minimum inhibitory concentration (31.25MUg/mL) against both Escherichia coli and
      Cryptococcus neoformans. The antimicrobial activities of this novel compound are
      reported here for the first time.

PMID- 29458848
TI  - A glucanolytic Pseudomonas sp. associated with Smilax bona-nox L. displays strong
      activity against Phytophthora parasitica.
AB  - Biological control is an eco-friendly strategy for mitigating and controlling
      plant diseases with negligible effects on human health and environment.
      Biocontrol agents are mostly isolated from field crops, and microbiomes
      associated with wild native plants is underexplored. The main objective of this
      study was to characterize the bacterial isolates associated with Smilax bona-nox
      L, a successful wild plant with invasive growth habits. Forty morphologically
      distinct bacterial isolates were recovered from S. bona-nox. Based on 16S rRNA
      gene sequencing, these isolates belonged to 12 different genera namely
      Burkholderia, Pseudomonas, Xenophilus, Stenotrophomonas, Pantoea,
      Enterobactriaceae, Kosakonia, Microbacterium, Curtobacterium, Caulobacter,
      Lysinibacillus and Bacillus. Among them, Pseudomonas sp. EA6 and Pseudomonas sp.
      EA14 displayed the highest potential for inhibition of Phytophthora. Based on
      sequence analysis of rpoD gene, these isolates revealed a 97% identity with a
      Pseudomonas fluorescence strain. Bioactivity-driven assays for finding bioactive
      compounds revealed that crude proteins of Pseudomonas sp. EA6 inhibited mycelial
      growth of P. parasitica, whereas crude proteins of Pseudomonas sp. EA14 displayed
      negligible activity. Fractionation and enzymatic analyses revealed that the
      bioactivity of Pseudomonas sp. EA6 was mostly due to glucanolytic enzymes.
      Comparison of chromatographic profile and bioactivity assays indicated that the
      secreted glucanolytic enzymes consisted of beta-1,3 and beta-1,4 glucanases,
      which acted together in hydrolyzing Phytophthora cell walls. Since the biological
      activity of the crude glucanolytic extract was >60-fold higher than the purified
      beta-1,3 glucanase, the glucanolytic enzyme system of Pseudomonas sp. EA6 likely
      acts synergistically in cell wall hydrolysis of P. parasitica.

PMID- 29458850
TI  - For the greater good: Programmed cell death in bacterial communities.
AB  - For a long a time programmed cell death was thought to be a unique characteristic
      of higher eukaryotes, but evidence has accumulated showing that programmed cell
      death is a universal phenomenon in all life forms. Many different types of
      bacterial programmed cell death systems have been identified, rivalling the
      eukaryotic systems in diversity. Bacteria are singular, seemingly independently
      living organisms, however they are part of complex communities. Being part of a
      community seems indispensable for survival in different environments. This review
      is focussed on the mechanism of and reasons for bacterial programmed cell death
      in the context of bacterial communities.

PMID- 29458849
TI  - Multifarious plant growth promotion by an entomopathogenic fungus Lecanicillium
      psalliotae.
AB  - An entomopathogenic fungus, Lecanicillium psalliotae strain IISR-EPF-02
      previously found infectious to cardamom thrips, Sciothrips cardamomi promoted
      plant growth in cardamom, Elettaria cardamomum. The isolate exhibited direct
      plant growth promoting traits by production of indole-3-acetic acid and ammonia
      and by solubilizing inorganic phosphate and zinc. It also showed indirect plant
      growth promoting traits by producing siderophores and cell wall-degrading enzymes
      like, alpha-amylases, cellulases and proteases. In pot culture experiments,
      application of the fungus at the root zone of cardamom seedlings significantly
      increased shoot and root length, shoot and root biomass, number of secondary
      roots and leaves and leaf chlorophyll content compared to untreated plants. This
      is the first report on the plant growth promoting traits of this fungus. The
      entomopathogenic and multifarious growth promoting traits of L. psalliotae strain
      IISR-EPF-02 suggest that it has great potential for exploitation in sustainable
      agriculture.

PMID- 29458851
TI  - Combination of multilocus sequence typing and pulsed-field gel electrophoresis
      reveals an association of molecular clonality with the emergence of extensive
      drug resistance (XDR) in Salmonella.
AB  - Salmonellae is one of the most important foodborne pathogens and becomes
      resistant to multiple antibiotics, which represents a significant challenge to
      food industry and public health. However, a molecular signature that can be used
      to distinguish antimicrobial resistance profile, particularly multi-drug
      resistance or extensive-drug resistance (XDR). In the current study, 168 isolates
      from the chicken and pork production chains and ill chickens were characterized
      by serotyping, antimicrobial susceptibility test, multilocus sequence typing
      (MLST) and pulsed-field gel electrophoresis (PFGE). The results showed that these
      isolates belonged to 13 serotypes, 14 multilocus sequence types (STs), 94 PFGE
      genotypes, and 70 antimicrobial resistant profiles. S. Enteritidis, S. Indiana,
      and S. Derby were the predominant serotypes, corresponding to the ST11, ST17, and
      ST40 clones, respectively and the PFGE Cluster A, Cluster E, and Cluster D,
      respectively. Among the ST11-S. Enteritidis (Cluster A) and the ST40-S. Derby
      (Cluster D) clones, the majority of isolates were resistant to 4-8 antimicrobial
      agents, whereas in the ST17S. Indiana (Cluster E) clone, isolates showed
      extensive-drug resistance (XDR) to 9-16 antimicrobial agents. The blaTEM-1-like
      gene was prevalent in the ST11 and ST17 clones corresponding to high ampicillin
      resistance. The blaTEM-1-like, blaCTX-M, blaOXA-1-like, sul1, aaC4, aac(6')-1b,
      dfrA17, and floR gene complex was highly prevalent among isolates of ST17,
      corresponding to an XDR phenotype. These results demonstrated the association of
      the resistant phenotypes and genotypes with ST clone and PFGE cluster. Our
      results also indicated that the newly identified gene complex comprising blaTEM-1
      like, blaCTX-M, blaOXA-1-like, sul1, aaC4, aac(6')-1b, dfrA17, and floR, was
      responsible for the emergence of the ST17S. Indiana XDR clone. ST17 could be
      potentially used as a molecular signature to distinguish S. Indiana XDR clone.

PMID- 29458852
TI  - Functional characterization of murB-potABCD operon for polyamine uptake and
      peptidoglycan synthesis in Streptococcus suis.
AB  - Spermidine (Spd), spermine (Spm), and putrescine (Put), which are the most widely
      distributed cellular polyamines, are essential for normal growth and
      multiplication of both eukaryotic and prokaryotic cells. In this study, we
      identified the only putative polyamine transport system PotABCD in Streptococcus
      suis, a worldwide zoonotic Gram-positive pathogen causing lethal infections in
      humans and pigs. It was discovered that S. suis could uptake polyamines
      preferably Spd and Spm. By constructing a potA deleted mutant, we confirmed that
      PotABCD was responsible for polyamine uptake, and PotD bound to the protein of
      polyamines. The four PotABCD genes were co-transcribed with murB, a gene involved
      in peptidoglycan (PG) synthesis. Furthermore the roles of polyamine transport
      system in maintaining the PG structure were detected to understand the biological
      significance of this co-transcription. In contrast to the wild type, the mutant
      DeltapotA exhibited elongated chain length and abnormal cell division morphology.
      Phenotypic changes were attributed to be the up-regulation of genes involved in
      PG synthesis and hydrolysis in DeltapotA. Additionally, polyamines functioned not
      only as feedback regulators of PotA by inhibiting PotA activity but also as
      regulators on potABCD and genes involved in PG synthesis. This study reveals the
      functions of PotABCD in polyamine transport and the regulatory roles of
      polyamines in PG synthesis. Results provide new insights into the machineries
      contributing to normal growth and cell division of S. suis.

PMID- 29458853
TI  - Fusarium species as pathogen on orchids.
AB  - The recent surge in demand for exotic ornamental crops such as orchids has led to
      a rise in international production, and a sharp increase in the number of plant
      and plant products moving between countries. Along with the plants, diseases are
      also being transported and introduced into new areas. Fusarium is one of the
      major diseases causing pathogens infecting orchids that is spreading through
      international trade. Studies have identified several species of Fusarium
      associated with orchids, some are pathogenic and cause symptoms such as leaf and
      flower spots, leaf or sheath blights, pseudostem or root rots, and wilts.
      Infection and damage caused by Fusarium reduces the quality of plants and
      flowers, and can cause severe economic losses. This review documents the current
      status of the Fusarium-orchid interaction, and illustrates challenges and future
      perspectives based on the available literature. This review is the first of
      Fusarium and orchid interactions, and integrates diverse results that both
      furthers the understanding and knowledge of this disease complex, and will enable
      the development of effective disease management practices.

PMID- 29458854
TI  - 5-hydroxymethyl-2-furaldehyde from marine bacterium Bacillus subtilis inhibits
      biofilm and virulence of Candida albicans.
AB  - Candida albicans is considered as the primary etiologic agent of candidiasis, a
      very common fungal infection in human. The yeast to hyphal transition and ability
      to form hypoxic biofilm on medical devices is well allied with virulence and
      antifungal resistance of C. albicans. Antagonistic agents that inhibit biofilm
      formation and alter susceptibility of C. albicans to conventional antifungals is
      of profound need. The present study explores the antibiofilm efficacy of Bacillus
      subtilis, a marine bacterial isolate from Palk Bay against C. albicans. Mass
      spectrometric analysis of ethyl acetate extract of B. subtilis unveiled 5
      hydroxymethyl-2-furaldehyde (5HM2F) as one of its major components. 5HM2F
      demonstrated concentration dependent biofilm inhibition, which was also
      corroborated through microscopic analysis. Furthermore, 5HM2F was effective in
      inhibiting other virulence factors of C. albicans such as morphological
      transition and secreted hydrolases production. Fourier transform infrared
      spectroscopic analysis showed alteration in amide bond region. The reduction in
      ergosterol content and increased antifungal susceptibility was well allied with
      real time PCR result, which showed down regulation of genes involved in drug
      resistance mechanisms. In vivo study using Caenorhabditis elegans also
      substantiated the antivirulence efficacy of 5HM2F at in vivo condition. Thus, the
      present study reports the therapeutic potential of 5HM2F against C. albicans
      infections.

PMID- 29458855
TI  - Streptomyces puniceus strain AS13., Production, characterization and evaluation
      of bioactive metabolites: A new face of dinactin as an antitumor antibiotic.
AB  - A highly active actinobacterial strain isolated from untapped areas of
      Northwestern Himalayas and characterised as Streptomyces puniceus strain AS13 by
      16S rRNA gene sequencing was selected for production of bioactive metabolites.
      The bioassay-guided fractionation of microbial cultured ethyl acetate extract of
      the strain, led to isolation of macrotetrolide compound 1 (Dinactin) and compound
      2 (1-(2,4-dihydroxy-6-methylphenyl)-ethanone). Structures of the isolated
      compounds were elucidated interpretation of NMR and other spectroscopic data
      including HR-ESI-MS, FT-IR. These compounds are reported for first time from
      Streptomyces Puniceus. Compound 1 exhibited strong anti-microbial activity
      against all tested bacterial pathogens including Mycobacterium tuberculosis. The
      MIC values of compound 1 against Gram negative and Gram positive bacterial
      pathogens ranged between 0.019 - 0.156MUgml-1 and 1MUgml-1 against Mycobacterium
      tuberculosis H37Rv. Dinactin exhibited marked anti-tumor potential with IC50 of
      1.1- 9.7MUM in various human cancerous cell lines and showed least cytotoxicity
      (IC50~80MUM) in normal cells (HEK-293). Dinactin inhabited cellular proliferation
      in cancer cells, reduced their clonogenic survival as validated by clonogenic
      assay and also inhabited cell migration and invasion characteristics in colon
      cancer (HCT-116) cells. Our results expressed the antimicrobial potential of
      dinactin and also spotted its prospective as an antitumor antibiotic.

PMID- 29458856
TI  - Evaluation of fungal community involved in the bioderioration process of wooden
      artworks and canvases in Montefeltro area (Marche, Italy).
AB  - Microbiological monitoring represents one of the most useful methods to assess
      potential risks related to the integrity of cultural heritage. The objective of
      this work was to evaluate the fungal community prevalent in 64 different artworks
      of Montefeltro area (Marche, central Italy). A total of 293 swabs were collected
      and, among these, 2.3% resulted negative to cultural method, while 87.7% were
      positive for the presence of filamentous fungi, yeasts and Actinomycetes.
      Totally, 11 genera and 12 different species were recovered from Sabouraud
      Dextrose Agar (SDA), Czapek Dox Agar (CDA), Malt Extract Agar (MEA), including 73
      strains of Mycelia sterilia. Penicillium spp. was isolated mostly from canvases
      (28.8%), while Aspergillus spp. was most present in wooden artworks (25.3%). SDA
      was the best performing medium with 57.1% of isolations, followed by CDA and MEA
      with percentages of 24.8 and 18.1% respectively. This study could be useful to
      better understand the microorganism-related phenomena in cultural heritage of
      Marche region, identifying the potential risks and defining preventive protecting
      such as climate control, frequent cleaning and environmental monitoring.

PMID- 29458857
TI  - Revealing the inhibitory potential of Yersinia enterocolitica on cysteine
      proteases of the papain family.
AB  - Cysteine proteases of the papain family, including mammalian cathepsins, play
      important physiological roles, however, their excessive activity may contribute
      to the development of various pathologies. Therefore, cysteine cathepsin
      inhibitors are being considered as promising drugs to treat cathepsin-driven
      diseases. Diverse saprophytic and parasitic microbes produce such inhibitors,
      which target the host's proteases playing pivotal roles in immune responses, thus
      leading to the survival of microbes within their host. Yersinia enterocolitica is
      a Gram-negative zoopathogenic coccobacillus, which has developed several
      mechanisms to evade the host's immune system. Nevertheless, the bacterium has not
      yet been shown to produce any cysteine protease inhibitors. Here we demonstrate
      that Y. enterocolitica strains of different bioserotypes and genotypes synthesize
      papain and human cathepsin L inhibitors, but not bovine cathepsin B inhibitors.
      By employing fluorimetry and zymography, the cell-surface inhibitors were shown
      to associate peripherally with the outer membrane, while the inhibitors present
      in cell-free extracts proved to: interact reversibly with their target enzymes,
      exhibit thermolability and stability in a range of pH values (5-9), and have high
      molecular weights. Batch affinity chromatography on papain-agarose resin was then
      undertaken to isolate putative inhibitors of cysteine proteases from the
      bacterial extract. The isolated 18 kDa protein was identified by LC-MS/MS as the
      periplasmic chaperone Skp. The Skp-containing eluate inhibited the activity of
      cysteine cathepsins produced by human dermal fibroblasts. The homologous Skp
      protein was also isolated from the extract of Escherichia coli. Our results point
      to a possible new biological role of the bacterial chaperone Skp.

PMID- 29458858
TI  - Monitoring biocalcification potential of Lysinibacillus sp. isolated from
      alluvial soils for improved compressive strength of concrete.
AB  - The present study reports the potential of newly isolated calcite precipitating
      bacteria isolated from alluvial soil to improve the strength and durability of
      concrete. A total of sixteen samples of alluvial soil and sewage were collected
      from the different locations of province Solan (India). For isolation, enrichment
      culture technique was used to enrich calcite precipitating strains in Urea broth.
      After enrichment, fourteen distinct bacterial strains were obtained on Urea agar.
      Based on qualitative and quantitative screening for urease activity, five
      isolates were obtained possessing higher calcite formation and urease activities
      (38-77 MUmhos/cm) as compared with standard strain of Bacillus megaterium MTCC
      1684 (77 MUmhos/cm). An isolate I13 identified as Lysinibacillus sp. was selected
      for self healing property in the concrete mix of M20. An improved compressive
      strength of 1.5 fold was observed in concrete samples amended with Lysinibacillus
      sp. over the concrete amended with B. megaterium MTCC 1684 after 28 days of
      curing. The higher calcite precipitation activity was indicated in Lysinibacillus
      sp. by FE-SEM micrographs and EDX analysis.

PMID- 29458859
TI  - The opportunistic human fungal pathogen Candida albicans promotes the growth and
      proliferation of commensal Escherichia coli through an iron-responsive pathway.
AB  - Candida albicans is a commensal fungal species that commonly colonizes a
      heterogeneous mixture of human body where it intimately interacts with other
      microbes in the host environment such as the gastrointestinal (GI) tract. Most
      studies in fungal-bacterial interactions are about synergistic or antagonistic
      effects of bacterial functions on fungal physiological activities including
      pathogenicity. Very few studies have been demonstrated about the role of fungi on
      bacteria. In this study, we investigated the interactions between C. albicans and
      the bacterium Escherichia coli and unexpectedly observed that C. albicans
      enhances growth and proliferation of Escherichia coli strain K12 by facilitating
      its cell division. Importantly, we found, based on our genetic screens, that both
      fungus- and bacterium-derived factors, including the iron-responsive
      transcription factors Sef1 and Sfu1 in C. albicans and the siderophere
      enterobactin transporters FepD and FepG in E. coli, actively contribute to this
      transkingdom interaction. Deletion of SFU1 or SEF1 caused a dramatic reduction in
      growth enhancement of E. coli. Compared to the wild type E. coli, the enhanced
      growth of both fepD and fepG null mutants were largely dampened. However, the E.
      coli mutant lacking entB, a key enzyme catalyzing the biosynthesis of siderophore
      enterobactin, showed similar growth enhancement as the wild type when co
      inoculated with C. albicans. C. albicans promotes growth and proliferation of the
      commensal bacterium E. coli and an iron-responsive signaling pathway appears to
      be required. C. albicans may act to supply a siderophere-like molecule that
      captures the environmental iron to promote the growth of E. coli. Our studies
      gave insight into a novel interacting mechanism operative in interspecies
      communication that occurs when bacteria and fungi co-exist.

PMID- 29458860
TI  - Could FlhF be a key element that controls Campylobacter jejuni flagella
      biosynthesis in the initial assembly stage?
AB  - The disordered arrangement of flagella biosynthetic genes, combined with a
      simplified regulatory mechanism, has made elucidating the process of
      Campylobacter jejuni flagellation difficult. FlhF is a recently identified
      element that controls the assembly of the flagella, although its function
      mechanism and regulatory preference are not well defined at present. In this
      study, we found that inactivation of FlhF caused the transcription of most
      flagella genes down-regulated. The importance of FlhF was systematically
      evaluated by analyzing changes in the transcription profiles between wild-type
      and flhF mutant strains, which showed that FlhF affects late flagella genes
      obviously. FlhF is constitutively expressed during C. jejuni growth,
      demonstrating that it is a class I flagella element that participates in early
      flagella assembly. In addition, the early flagella component FlhB was not
      localized to the cell pole in the flhF mutant. Thus, flagella assembly was
      impeded at the initial stage. We propose a model in which FlhF helps target the
      early flagella components to the cell pole, functioning prior to the formation of
      the flagella export apparatus, and thus places FlhF at the top of the flagella
      regulatory cascade hierarchy. Inactivation of FlhF impeded flagella assembly at
      the initial stage and decreased transcription of flagella genes through a feed
      back control mechanism, leading to FlhF having a significant influence on the
      expression of late flagella components and resulting in the aflagellate C. jejuni
      phenotype. Our present study has uncovered how FlhF influences C. jejuni flagella
      biosynthesis, which will be helpful in understanding the C. jejuni flagella
      biosynthetic pathway and bacterial flagellation in general.

PMID- 29458861
TI  - First report of a cross-kingdom pathogenic bacterium, Achromobacter xylosoxidans
      isolated from stipe-rot Coprinus comatus.
AB  - Coprinus comatus is an edible mushroom widely cultivated in China as a delicious
      food. Various diseases have occurred on C. comatus with the cultivated area
      increasing. In this study, the pathogenic bacterium JTG-B1, identified as
      Achromobacter xylosoxidans by 16S rDNA and nrdA gene sequencing, was isolated
      from edible mushroom Coprinus comatus with serious rot disease on its stipe. A.
      xylosoxidans has been confirmed as an important opportunistic human pathogenic
      bacterium and has been isolated from respiratory samples from cystic fibrosis. It
      is widely distributed in the environment. Here, we first report that fungi can
      also serve as a host for A. xylosoxidans. We confirmed that it can cross-kingdom
      infect between animals (mice) and fungi (C. comatus). The results of
      pathogenicity tests, physiological, biochemical and genotyping analysis of A.
      xylosoxidans from different hosts suggested that different strain of A.
      xylosoxidans may have pathogenicity differentiation. A. xylosoxidans not only is
      pathogenic to C. comatus but also may threaten human health.

PMID- 29458862
TI  - Comparative transcriptomic analysis of Cerrena unicolor revealed differential
      expression of genes engaged in degradation of various kinds of wood.
AB  - To explore the number of enzymes engaged by Cerrena unicolor FCL139 for wood
      degradation, the transcriptomes of the fungus growing on birch, ash, maple
      sawdust and the control liquid medium were analyzed. Among 12,966 gene models
      predicted for the C. unicolor genome, 10,396 all-unigenes were detected, of which
      9567 were found to be expressed in each of the tested growth media. The highest
      number (107) of unique transcripts was detected during fungus growth in the
      control liquid medium, while the lowest number (11) - in the fungal culture
      comprising maple saw dust. Analysis of C. unicolor transcriptomes identified
      numerous genes whose expression differed substantially between the mycelia
      growing in control medium and each of the sawdust media used, with the highest
      number (828) of upregulated transcripts observed during the fungus growth on the
      ash medium. Among the 294 genes that were potentially engaged in wood
      degradation, the expression of 59 was significantly (p < .01) changed in the
      tested conditions. The transcripts of 37 of those genes were at least four times
      more abundant in the cells grown in all sawdust media when compared to the
      control medium. Upregulated genes coding for cellulases and, to a lower extent,
      hemicellulases predominated during fungus growth on sawdust. Transcripts encoding
      cellulolytic enzymes were the most abundant in mycelia grown on birch and maple
      while lower number of such transcripts was detected in fungus growing on ash. The
      expression pattern of lignolytic activities-coding genes was strongly dependent
      on the type of sawdust applied for fungus growth medium.

PMID- 29458863
TI  - Genetic manipulation of Fonsecaea pedrosoi using particles bombardment and
      Agrobacterium mediated transformation.
AB  - Fonsecaea pedrosoi, a melanized fungal pathogen that causes Chromoblastomycosis,
      a human disease with a worldwide distribution. Biolistic is a widely used
      technique for direct delivery of genetic material into intact cells by particles
      bombardment. Another well-established transformation method is Agrobacterium
      mediated transformation (ATMT), which involves the transfer of a T-DNA from the
      bacterium to the target cells. In F. pedrosoi there are no reports of established
      protocols for genetic transformation, which require optimization of physical and
      biological parameters. In this work, intact conidia of F. pedrosoi were particle
      bombarded and subjected to ATMT. In addition, we proposed hygromycin B,
      nourseothricin and neomycin as dominant selective markers for F. pedrosoi and
      vectors were constructed. We tested two parameters for biolistic: the distance of
      the particles to the target cells and time of cells recovery in nonselective
      medium. The biolistic efficiency was 37 transformants/MUg of pFpHYG, and 45
      transformants/MUg of pAN7.1. Transformants expressing GFP were successfully
      obtained by biolistic. A co-culture ratio of 10: 1 (bacterium: conidia) and co
      incubation time of 72 h yielded the largest number of transformants after ATMT.
      Southern blot analysis showed the number of foreign DNA insertion into the genome
      is dependent upon the plasmid used to generate the mutants. This work describes
      for the first time two efficient methods for genetic modification of Fonsecaea
      and these results open new avenues to better understand the biology and
      pathogenicity of the main causal agent of this neglected disease.

PMID- 29458864
TI  - Functional analysis of an APSES transcription factor (GlSwi6) involved in fungal
      growth, fruiting body development and ganoderic-acid biosynthesis in Ganoderma
      lucidum.
AB  - The APSES transcription factors have been identified as key regulators of fungal
      development and other biological processes in fungi. In the present study, the
      function of Ganoderma lucidum GlSwi6, a homolog of Saccharomyces cerevisiae Swi6,
      was characterized. RNAi was used to examine the function of GlSwi6 in G. lucidum.
      Silencing GlSwi6 resulted in multiple developmental defects, including reduced
      fungal growth and increased hyphal branching, and the GlSwi6-silenced strains did
      not exhibit primordium or fruiting body formation. In addition, the H2O2 and
      ganoderic-acid (GA) levels of the GlSwi6-silenced strains decreased approximately
      50% and 25%, respectively, compared with those of the WT strain. Furthermore, the
      addition of H2O2 led to the recovery of the GA levels of GlSwi6-silenced strains,
      implying that GlSwi6 might regulate GA biosynthesis by regulating the
      intracellular ROS levels. Taken together, these results indicate that GlSwi6 is
      involved in fungal growth, development and GA biosynthesis in G. lucidum.

PMID- 29458865
TI  - Diversity and bioprospecting of extremely halophilic archaea isolated from
      Algerian arid and semi-arid wetland ecosystems for halophilic-active hydrolytic
      enzymes.
AB  - The diversity of haloarchaea associated with different dry salt lakes in
      northeastern Algeria was investigated together with their potential of hydrolytic
      enzyme production. A total of 68 aerobic halophilic archaea were isolated from
      saline sediments. Based on the 16S rRNA gene sequencing, the isolates were
      assigned to seven phylotypes within the class Halobacteria, namely Haloarcula,
      Halococcus, Haloferax, Halogeometricum, Haloterrigena, Natrialba, and Natrinema.
      The results showed that Haloferax group was found to be dominant in all samples
      (30 isolates) (44%) with high diversity, followed by Halococcus spp. (13%) (9
      isolates). All phylotypes are extreme halophiles and thermotolerant with the
      ability to grow at temperatures up to 48  degrees C. In addition, the screening
      for extracellular halophilic enzymes showed that 89.7% of the isolates were able
      to produce at least two types of the screened enzymes. The strains producing
      esterase, gelatinase, inulinase, cellulase and protease activities were the most
      diverse functional group. These data showed an abundant and diverse haloarchaeal
      community, detected in Algerian wetland ecosystems, presenting a promising source
      of molecules with important biotechnological applications.

PMID- 29458866
TI  - Reactive oxygen species-independent apoptotic pathway by gold nanoparticles in
      Candida albicans.
AB  - Candida albicans is the most common pathogenic fungus in humans, causing
      cutaneous and life-threatening systemic infections. In this study, we confirmed
      using propidium iodide influx that gold nanoparticles (AuNPs), which are
      promising materials for use as antimicrobial agents, did not affect the membrane
      permeability of C. albicans. Thus, the fungal cell death mechanisms induced by
      AuNPs were assessed at intracellular levels including DNA damage, mitochondrial
      dysfunction, and reactive oxygen species (ROS) overproduction. AuNPs interacted
      with C. albicans DNA leading to increased nuclear condensation and DNA
      fragmentation. Changes in the mitochondria induced by AuNPs involving mass, Ca2+
      concentrations, and membrane potential indicated dysfunction, though the level of
      intracellular and mitochondrial ROS were maintained. Although ROS signaling was
      not disrupted, DNA damage and mitochondrial dysfunction triggered the release of
      mitochondrial cytochrome c into the cytosol, metacaspase activation, and
      phosphatidylserine externalization. Additionally, the AuNPs-induced apoptotic
      pathway was not influenced by N-acetylcysteine, an ROS scavenger. This indicates
      that ROS signaling is not linked with the apoptosis. In conclusion, AuNPs induce
      ROS-independent apoptosis in C. albicans by causing DNA damage and mitochondria
      dysfunction.

PMID- 29458867
TI  - Does plant-Microbe interaction confer stress tolerance in plants: A review?
AB  - The biotic and abiotic stresses are major constraints for crop yield, food
      quality and global food security. A number of parameters such as physiological,
      biochemical, molecular of plants are affected under stress condition. Since the
      use of inorganic fertilizers and pesticides in agriculture practices cause
      degradation of soil fertility and environmental pollutions. Hence it is necessary
      to develop safer and sustainable means for agriculture production. The
      application of plant growth promoting microbes (PGPM) and mycorrhizal fungi
      enhance plant growth, under such conditions. It offers an economically
      fascinating and ecologically sound ways for protecting plants against stress
      condition. PGPM may promote plant growth by regulating plant hormones, improve
      nutrition acquisition, siderophore production and enhance the antioxidant system.
      While acquired systemic resistance (ASR) and induced systemic resistance (ISR)
      effectively deal with biotic stress. Arbuscular mycorrhiza (AM) enhance the
      supply of nutrients and water during stress condition and increase tolerance to
      stress. This plant-microbe interaction is vital for sustainable agriculture and
      industrial purpose, because it depends on biological processes and replaces
      conventional agriculture practices. Therefore, microbes may play a key role as an
      ecological engineer to solve environmental stress problems. So, it is a feasible
      and potential technology in future to feed global population at available
      resources with reduced impact on environmental quality. In this review, we have
      attempted to explore about abiotic and biotic stress tolerant beneficial
      microorganisms and their modes of action to enhance the sustainable agricultural
      production.

PMID- 29458869
TI  - Corrigendum to "Targets of ubiquitin like system in mycobacteria and related
      actinobacterial species" [Microbiol. Res. 204 (November 2017) 9-29].

PMID- 29458868
TI  - Stress response of a clinical Enterococcus faecalis isolate subjected to a novel
      antimicrobial surface coating.
AB  - Emerging antibiotic resistance among pathogenic bacteria, paired with their
      ability to form biofilms on medical and technical devices, represents a serious
      problem for effective and long-term decontamination in health-care environments
      and gives rise to an urgent need for new antimicrobial materials. Here we present
      the impact of AGXX(r), a novel broad-spectrum antimicrobial surface coating
      consisting of micro-galvanic elements formed by silver and ruthenium, on the
      transcriptome of Enterococcus faecalis. A clinical E. faecalis isolate was
      subjected to metal stress by growing it for different periods in presence of the
      antimicrobial coating or silver-coated steel meshes. Subsequently, total RNA was
      isolated and next-generation RNA sequencing was performed to analyze variations
      in gene expression in presence of the antimicrobial materials with focus on known
      stress genes. Exposure to the antimicrobial coating had a large impact on the
      transcriptome of E. faecalis. After 24min almost 1/5 of the E. faecalis genome
      displayed differential expression. At each time-point the cop operon was strongly
      up-regulated, providing indirect evidence for the presence of free Ag+-ions.
      Moreover, exposure to the antimicrobial coating induced a broad general stress
      response in E. faecalis. Genes coding for the chaperones GroEL and GroES and the
      Clp proteases, ClpE and ClpB, were among the top up-regulated heat shock genes.
      Differential expression of thioredoxin, superoxide dismutase and glutathione
      synthetase genes indicates a high level of oxidative stress. We postulate a
      mechanism of action where the combination of Ag+-ions and reactive oxygen species
      generated by AGXX(r) results in a synergistic antimicrobial effect, superior to
      that of conventional silver coatings.

PMID- 29458870
TI  - Rapid screening of starter cultures for maari based on antifungal properties.
AB  - Forty Bacillus isolates obtained from maari (used as condiment in Burkina Faso)
      including 17 B. subtilis, 4 B. circulans, 7 B. pumilus and 6 B. licheniformis
      were investigated for use as starter cultures in maari production. The isolates
      were screened by PCR for the sfp gene responsible for the production of the
      lipopeptide biosurfactant, surfactin. The sfp gene was detected in all of the
      seventeen B. subtilis isolates, in 2 out of 7 B. pumilus, in 4 out of 6 B.
      licheniformis whereas no B. circulans was positive for the sfp gene by PCR
      screening. Furthermore, all the 40 Bacillus spp. were screened for biosurfactant
      production and inhibitory activity against Aspergillus flavus, A. niger, A.
      versicolor and Rhizopus oryzae. Results demonstrated a relationship between the
      presence of the sfp gene and the antifungal activity and biosurfactant production
      of Bacillus isolates. In addition, molecular typing of the 17 B. subtilis
      isolates by Multilocus Sequence Typing (MLST) resulted in 15 Sequence Types, one
      of them included three strains. Randomly Amplified Polymorphic DNA-PCR (RAPD
      PCR), used for B. licheniformis, B. megaterium, B. circulans and B. pumilus
      revealed that the inhibitory activity and biosurfactant production were strain
      dependent. Finally, the detection of chitinase (chi) and beta-glucanase (glu)
      biosynthesis genes was found to be associated with the antifungal activity for 16
      B. subtilis isolates. The present work provides a greater understanding of the
      antifungal activity and biosurfactant production ability within the Bacillus spp.
      isolated from maari and contributes to the selection of Bacillus isolates to be
      used as starter cultures for controlled production of maari.

PMID- 29458871
TI  - DNA sequence-specific dimeric bisbenzimidazoles DBP(n) and DBPA(n) as inhibitors
      of H-NS silencing in bacterial cells.
AB  - DNA sequence-specific fluorescent dimeric bisbenzimidazoles DBP(n) and DBPA(n),
      noncovalently interacting with A-T pairs in the minor groove of double-stranded
      DNA were used for studying and monitoring the expression of histone-like H-NS
      dependent promoters. Histone-like H-NS selectively binds to AT-rich segments of
      DNA and silences a large number of genes in bacterial chromosomes. The H-NS
      dependent promoters of Quorum Sensing (QS)-regulated lux operons of the marine
      bacteria mesophilic Aliivibrio fischeri, psychrophilic Aliivibrio logei were
      used. Escherichia coli lux biosensors were constructed by cloning fragments
      bearing QS-regulated promoters into the vector, thereby placing each fragment
      upstream of the promoterless Photorhabdus luminescens luxCDABE genes. It was
      shown that the dimeric bisbenzimidazoles DBP(n) and DBPA(n) counteract the H-NS
      silencing activity. Thus, the presence of DBP(n) or DBPA(n) in the medium leads
      to an approximately 10-100-fold increase in the level of transcription of QS
      promoters in E. coli hns+. The largest decrease in the level of H-NS repression
      was observed using ligands containing a linker with a length of ca. 18A, such as
      DBP(2) and DBPA(2). Ligands containing linkers with n=1 and 3 are an order of
      magnitude less active; ligands with n=4 are inactive. DBPA(2) exhibits activity
      starting with a concentration of 0.5MUM; the minimum concentration of DBP(2) is 5
      7 times higher. It is suggested that A-T pairs located at five nucleotide pair
      intervals, which correspond to the linker length in highly active ligands with
      n=2, play a key role in the structure of H-NS-binding sites in QS-regulated
      promoters.

PMID- 29458872
TI  - Diversity of cultivable bacterial endophytes in Paullinia cupana and their
      potential for plant growth promotion and phytopathogen control.
AB  - Endophytic bacteria occupy the same niche of phytopathogens and may produce
      metabolites that induce the host plant systemic resistance and growth. Host and
      environmental variables often determine the endophytic community's structure and
      composition. In this study, we addressed whether the plant genotype, organ, and
      geographic location influence the structure, composition, and functionality of
      endophytic bacterial communities in Paullinia cupana. To characterize the
      communities and identify strains with potential application in agriculture, we
      analyzed two P. cupana genotypes cultivated in two cities of the State of
      Amazonas, Brazil. Endophytic bacteria were isolated from surface-disinfested
      root, leaf, and seed tissues through the fragmentation and maceration techniques.
      The colonization rate, number of bacteria, richness, diversity, and functional
      traits were determined. The plant growth-promoting ability of selected bacterial
      strains was assessed in Sorghum bicolor. We identified 95 bacterial species
      distributed in 29 genera and 3 phyla (Proteobacteria, Actinobacteria, and
      Firmicutes). The colonization rate, richness, diversity, and species composition
      varied across the plant organs; the last parameter also varied across the plant
      genotype and location. Some strains exhibited relevant plant growth-promoting
      traits and antagonistic traits against the main phytopathogens of P. cupana, but
      they were not separated by functional traits. The main bacterial strains with
      plant growth-promoting traits induced S. bicolor growth. Altogether, our findings
      open opportunities to study the application of isolated endophytic bacterial
      strains in the bioprospection of processes and products.

PMID- 29458873
TI  - A review on sustainable yeast biotechnological processes and applications.
AB  - Yeast is very well known eukaryotic organism for its remarkable biodiversity and
      extensive industrial applications. Saccharomyces cerevisiae is one of the most
      widely used microorganisms in biotechnology with successful applications in the
      biochemical production. Biological conversion with the focus on the different
      utilization of renewable feedstocks into fuels and chemicals has been intensively
      investigated due to increasing concerns on sustainability issues worldwide.
      Compared with its counterparts, Saccharomyces cerevisiae, the baker's yeast, is
      more industrially relevant due to known genetic and physiological background, the
      availability of a large collection of genetic tools, the compatibility of high
      density and large-scale fermentation, and optimize the pathway for variety of
      products. Therefore, S. cerevisiae is one of the most popular cell factories and
      has been successfully used in the modern biotech industry to produce a wide
      variety of products such as ethanol, organic acids, amino acids, enzymes, and
      therapeutic proteins. This study explores how different sustainable solutions
      used to overcome various environmental effects on yeast. This work targets a
      broad matrix of current advances and future prospect in yeast biotechnology and
      discusses their application and potential in general.

PMID- 29458875
TI  - Clinical and genetic-epignetic aspects of recurrent hydatidiform mole: A review
      of literature.
AB  - Hydatidiform Mole (HM) is the most common form of Gestational Trophoblastic
      Disease (GTD), defined by hyper-proliferation of trophoblastic cells. HM is
      typified as abnormal proliferation of extraembryonic trophoblastic (placental)
      tissues and failure of embryonic tissues development and is the only GTD with
      Mendelian inheritance, which can reoccur in different pregnancies. Moles are
      categorized into Complete Hydatidiform Moles (CHM) or Partial Hydatidiform Moles
      (PHM) and a rare familial trait, which forms a CHM and despite having
      androgenetic pattern, shows normal biparental inheritance, conceived from one
      sperm and egg. Recessive maternal-effect mutations in NLRP7 (NACHT, leucine rich
      repeat and PYD containing 7) and KHDC3L (KH Domain Containing 3-Like) genes have
      been shown to be responsible for Recurrent Hydatidiform Moles (HYDM1 MIM# 231090
      when is caused by mutation in the NLRP7 gene and HYDM2 MIM#614293 when is caused
      by mutation in the KHDC3L gene). Methylation aberration in multiple maternally
      imprinted genes is introduced as the cause of Recurrent HYDM pathology. The
      current article reviews the histopathology, risk factors, and genetic and
      epigenetic characteristics of Recurrent HYDMs.

PMID- 29458874
TI  - Comparative analysis of gut bacterial communities of green turtles (Chelonia
      mydas) pre-hospitalization and post-rehabilitation by high-throughput sequencing
      of bacterial 16S rRNA gene.
AB  - Stranded green turtles (Chelonia mydas) are often cared for in rehabilitation
      centers until they recover. Although the specific causal agents of diseases in
      stranded turtles are difficult to diagnose, we know that gut microbiota of green
      turtles play a vital role in health as well as a wide range of diseases. The
      objective of this study was to characterize and compare the gut bacterial
      communities between pre-hospitalization (PH) and post-rehabilitation (PR)
      stranded green turtles using high-throughput sequencing analysis targeting V1-V3
      regions of the bacterial 16S rRNA gene. A total of eight cloacal swab samples
      were collected from four green turtles undergoing rehabilitation. Proteobacteria
      dominating in both PH and PR samples without any significant difference.
      Firmicutes was the second and Bacteroidetes was the third most abundant phylum in
      PH samples, while Bacteroidetes prevailed in PR samples, followed by Firmicutes.
      The predominance of the genus Bacteroides in both PH and PR samples indicates the
      importance of this genus in turtle gut health. At a class level,
      Epsilonproteobacteria was significantly (P<0.05) associated with PH samples and
      Deltaproteobacteria predominated (P<0.05) in PR samples. The significant
      abundance of Campylobacter fetus, Escherichia coli, Clostridium botulinum and
      Vibrio parahaemolyticus in PH samples indicate pathogenic associations with
      stranded green turtles with zoonotic potential. The presence of Salmonella
      enterica in only PR samples suggest possible acquisition of this bacteria during
      rehabilitation. In this study, all post-rehabilitation green turtles exhibited
      similar bacterial communities, irrespective of their microbial compositions at
      pre-hospitalization. The marked differences in the gut bacterial communities of
      PH and PR turtles indicate the outcome of dietary, management and environmental
      shift during rehabilitation. Therefore, it is important to address the process of
      restoring normal gut microbiota of recovered turtles prior to release back to
      their natural habitat.

PMID- 29458876
TI  - Bone densitometry status and its associated factors in peri and post menopausal
      females: A cross sectional study from a tertiary care centre in India.
AB  - OBJECTIVE: Osteoporosis is a skeletal disorder characterized by diminished bone
      strength that increases the risk of fracture at instances of trivial trauma.
      Asians have a lower bone mass than the west. The present study was designed to
      add data from India on women above the age of 40 years with respect to low bone
      mineral density (BMD) and its associated high risk factors. MATERIALS AND
      METHODS: After a written informed consent, a detailed history was taken. Basal
      metabolic index was recorded, and biochemical and endocrine tests were done,
      followed by dual X ray absorptiometry scan. RESULTS: Average age of the study
      population was 46.54 years and BMI 26.58. The prevalence of osteopenia in the
      study was 36%, and that of osteoporosis, 4%; the overall prevalence of low BMD
      being 40%. Proportion of women with low BMD increased with advancing age and
      menopausal status. On endocrine evaluation, 53.44% cases with insufficient
      vitamin D, 62.5% with hyperparathyroidism, 100% with hypothyroidism, 75% with
      hyperthyroidism suffered from low BMD. Among chronic diseases, 75% women with
      diabetes, 33.3% with hypertension, 25% with deranged liver function and 50% with
      rheumatoid arthritis were found to have low BMD. 46.75% women with sun exposure
      less than one hour daily had poor bone mineralization. The proportion of women
      with normal BMD decreased from 84.09% to 43.33% with decrease in daily physical
      work. On logistic regression analysis, insufficient serum vitamin D
      concentrations, less physical work and inadequate sun exposure were found to be
      significantly associated with low BMD. CONCLUSION: Low BMD is not a disorder
      confined to postmenopausal women alone. It is widely prevalent in women above 40
      years of age. Screening women above 40 in the absence of any high risk factors
      has the potential of nipping this silent killer in the bud.

PMID- 29458877
TI  - 1p deletion syndrome: A prenatal diagnosis characterized by an abnormal 1st
      trimester combined screening test, yet a normal NIPT result.
AB  - OBJECTIVE: To present a case with prenatal diagnosis and cytogenetic
      characterization of 1p36 deletion syndrome whose first trimester combined testing
      is abnormal but a normal NIPT result. CASE REPORT: A 33-year-old had an abnormal
      1st trimester fetal aneuploidy screening result, but no trisomies 13, 18, 21 were
      detected by the noninvasive prenatal testing. Amniocentesis was performed after
      ultrasound showed fetal ventriculomegaly and echogenic bowel. The final
      conventional cytogenetics revealed a karyotype of 46, XX, del(1)(p36).
      CONCLUSION: Every prenatal genetic screening test and diagnostic procedure has
      its benefit and risk. NIPT offers better sensitivity and specificity for
      trisomies 13, 18, and 21. Even so, for primary population screening, NIPT
      provides lower detection rate than sequential screening if considering detection
      of all chromosomal abnormalities. Diagnostic testing should be offered rather
      than cell-free DNA screening to pregnant women if a fetal structural anomaly is
      identified on ultrasound examination.

PMID- 29458878
TI  - Variations in clinical presentation of unicornuate uterus with non-communicating
      rudimentary horn (class IIB of the American Fertility Society classification).
AB  - OBJECTIVE: The unicornuate uterus is a rare uterine malformation (2.4-13.7% of
      all uterine malformations (Engmann et al., 2004)) which usually features a
      rudimentary accessory horn in more than 75% of the cases. Pregnancy in the
      rudimentary horn is rare, but the complications attached to such pregnancies
      could be defined as the first clinical manifestation of rudimentary horn. CASE
      REPORTS: We hereby describe five cases of unicornuate uterus with rudimentary
      horn (UUWRH), each one with a different clinical presentation and without any
      correct preoperative diagnosis, and henceforth reflect on the practical aspects
      learnt about the differential diagnosis and management of this rare malformation.
      CONCLUSION: Our experience with UUWRH is that perhaps asymptomatic cases are not
      as rare as reported in medical literature. We highlight the need for a greater
      awareness of the differential diagnosis of genital malformations and accurate in
      the exact subtype and their correct treatment.

PMID- 29458879
TI  - A case of rapidly-growing atypical polypoid adenomyoma which was histologically
      diagnosed before operation and removed by a laparoscopic resection.
AB  - OBJECTIVE: Atypical polypoid adenomyoma (APAM) is an epithelial-mesenchymal mixed
      tumor which often develops in the uterine cavity of reproductive age women,
      requiring preservation of the reproductive functions. Preoperative endometrial
      biopsy may not yield histological diagnosis as the tumor is a solid smooth muscle
      tumor. The standard treatment option is a hysteroscopic resection for the
      diagnosis and the treatment at the same time. CASE REPORT: We report a case of
      rapidly-growing APAM successfully diagnosed preoperatively via transcervical
      punch biopsy followed by a laparoscopic resection. The mass was relatively large,
      had been located in the lower segment of the uterus, and the area of contact with
      the muscular layers was large. It was a complete removal and no recurrence had
      been observed 9 months after the operation. CONCLUSION: This is the first report
      of APAM treated by laparoscopic resection. The method may be a useful alternative
      when hysteroscopic surgery is inappropriate.

PMID- 29458880
TI  - Prenatal diagnosis of hydrancephaly and enlarged cerebellum and cisterna magna in
      a fetus with thanatophoric dysplasia type II and a review of prenatal diagnosis
      of brain anomalies associated with thanatophoric dysplasia.
AB  - OBJECTIVE: We present prenatal diagnosis of hydrancephaly and enlarged cerebellum
      and cisterna magna in a fetus with thanatophoric dysplasia type II (TD2) and a
      review of prenatal diagnosis of brain anomalies associated with TD. CASE REPORT:
      A 33-year-old woman was referred for genetic counseling at 25 weeks of gestation
      because of fetal ultrasound abnormalities. Prenatal ultrasound at 14 weeks of
      gestation revealed an increased nuchal translucency (NT) and hydrocephalus. Level
      II ultrasound examination at 25 weeks of gestation revealed hydrancephaly,
      macrocephaly, a cloverleaf skull, frontal bossing, enlarged cerebellum and
      cisterna magna, a narrow chest, small ribs, short straight limbs. Amniocentesis
      revealed a karyotype of 46,XX. FGFR3 mutation analysis using the DNA extracted
      from uncultured amniocytes revealed a genotype of WT/c.1948A>G (p.Lys650Glu). The
      result was consistent with a K650E mutation in FGFR3 and TD2. The pregnancy was
      subsequently terminated. CONCLUSION: Fetuses with TD2 may present increased NT,
      early onset hydrocephalus, enlarged cerebellum and cisterna magna, and
      hydrancephaly on prenatal ultrasound.

PMID- 29458881
TI  - Prenatal diagnosis of short-rib polydactyly syndrome type III or short-rib
      thoracic dysplasia 3 with or without polydactyly (SRTD3) associated with compound
      heterozygous mutations in DYNC2H1 in a fetus.
AB  - OBJECTIVE: We present the perinatal imaging findings and molecular genetic
      analysis in a fetus with short-rib polydactyly syndrome (SRPS) type III or short
      rib thoracic dysplasia 3 with or without polydactyly (SRTD3). CASE REPORT: A 29
      year-old, primigravid woman was referred for genetic counseling at 15 weeks of
      gestation because of abnormal ultrasound findings of short limbs, a narrow chest
      and bilateral polydactyly of the hands and feet, consistent with a diagnosis of
      SRPS type III. Chorionic villus sampling was performed, and targeted next
      generation sequencing (NGS) was applied to analyze a panel of 25 genes including
      CEP120, DYNC2H1, DYNC2LI1, EVC, EVC2, FGFR2, FGFR3, HOXD10, IFT122, IFT140,
      IFT172, IFT52, IFT80, KIAA0586, NEK1, PAPSS2, SLC26A2, SOX9, TCTEX1D2, TCTN3,
      TTC21B, WDR19, WDR34, WDR35 and WDR60. The NGS analysis identified novel
      mutations in the DYNC2H1 gene. The fetus was compound heterozygous for a missense
      mutation c.8077G > T (p.Asp2693Tyr) of paternal origin in DYNC2H1 and a
      frameshift mutation c.11741_11742delTT (p.Phe3914X) of maternal origin in
      DYNC2H1. The fetus had a karyotype of 46,XY, and postnatally manifested
      characteristic SRPS type III phenotype. CONCLUSION: Targeted NGS is useful in
      genetic diagnosis of fetal skeletal dysplasia and SRPS, and the information
      acquired is helpful in genetic counseling.

PMID- 29458882
TI  - Prenatal diagnosis of a 0.7-Mb 17p13.3 microdeletion encompassing YWHAE and CRK
      but not PAFAH1B1 in a fetus without ultrasound abnormalities.
AB  - OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic
      characterization of 17p13.3 microdeletion encompassing YWHAE and CRK but not
      PAFAH1B1 in a fetus without ultrasound abnormalities. CASE REPORT: A 33-year-old
      woman underwent amniocentesis at 17 weeks of gestation because of a family
      history of spinocerebellar atrophy in the husband. Amniocentesis revealed a
      karyotype of 46,XX. Simultaneously array comparative genomic hybridization (aCGH)
      analysis (using 60,000 probes) revealed a 0.7-Mb 17p13.3 microdeletion or arr
      17p13.3 (1,264,243-1,965,733) * 1 dn [GRCh37 (hg19)] encompassing YWHAE and CRK
      but not PAFAH1B1. Prenatal ultrasound findings were unremarkable. There were no
      structural abnormalities of the brain, heart, kidneys, skull, limbs and other
      internal organs. The parents elected to terminate the pregnancy, and a 268-g
      fetus was delivered at 19 weeks of gestation with mild facial dysmorphism.
      Postnatal high-resolution aCGH analysis of the placenta (using 630,000 probes)
      showed a 0.79-Mb 17p13.3 microdeletion or arr 17p13.3 (1,173,549-1,970,690) * 1
      (hg19) encompassing TUSC5, YWHAE, CRK and HIC1 but not PAFAH1B1. Metaphase
      fluorescence in situ hybridization analysis using the 17p13.3-specific probe of
      RP11-818O24 revealed a 17p13.3 deletion. CONCLUSION: Fetus with 17p13.3
      microdeletion without involving PAFAH1B1 may present no brain abnormalities on
      fetal ultra sound.

PMID- 29458883
TI  - Maternal and fetal outcomes in pregnancies with pulmonary hypertension:
      Experience of a tertiary center.
AB  - OBJECTIVE: Pregnancies complicated with PHT are serious debates for obstetricians
      due to high maternal and fetal complication potentials. The aim of the study was
      to present our maternofetal outcomes in pregnant women with pulmonary
      hypertension. MATERIALS AND METHODS: This study was performed using data
      extracted from the medical files of 23 pregnancies of 18 patients with PHT who
      were followed-up in the obstetrics and gynecology department. RESULTS: The
      average age was 27.09 +/- 6.97 (range: 14-38) years. The most frequent maternal
      cardiac pathologies were cardiac valvular disease (mitral or aortic
      insufficiency) (n = 4), atrial septal defect (n = 3), mitral stenosis (n = 3),
      ventricular septal defect (n = 2) and arrhythmia (n = 2). Caesarean section and
      normal vaginal delivery were performed in 13 and 7 deliveries, respectively.
      Therapeutic dilatation and curettage was performed in 3 patients. Preterm
      delivery occurred in 4 pregnancies and there were 2 intrauterine growth
      retardations, 1 preeclampsia and 2 maternal pulmonary edemas. One patient
      underwent re-laparotomy 5 days after delivery due to uterine hematoma. Totally,
      20 newborns (14 female, 6 male) were delivered. Most of the complications were
      seen in advanced PHT classes. CONCLUSION: The care of the pregnant women with PHT
      necessitates a well-planned, multidisciplinary approach focusing on close
      monitoring before, during and after delivery. This approach may contribute to
      reduction of poor maternal and fetal outcomes.

PMID- 29458884
TI  - Late-onset fetal bilateral pleural effusions associated with Down syndrome.
AB  - OBJECTIVE: We present two cases of late-onset bilateral fetal pleural effusions
      associated with fetal Down syndrome. CASE REPORTS: Case 1. A 33-year-old
      Vietnamese woman had undergone regular sonographic examinations since 23 weeks of
      gestation and no abnormality had been noted. However, bilateral moderate pleural
      effusions were found at 33 weeks of gestation, and massive pleural effusion,
      ascites and polyhydramnios developed at 34 weeks of gestation. Aspiration of the
      pleural effusion was subsequently performed. Clinical laboratory surveys of the
      aspiration fluid excluded toxoplasmosis and cytomegalovirus infection.
      Cytogenetic analysis of cultured lymphocytes derived from pleural effusion
      revealed a karyotype of 47,XX,+21. The parents elected to continue the pregnancy.
      Intrauterine fetal demise occurred at 37 weeks of gestation, and a macerated
      female baby was delivered. Postnatal cytogenetic analysis of the umbilical cord
      confirmed the prenatal diagnosis. Case 2. A 41-year-old Pakistani woman had
      undergone regular sonographic examinations and no abnormality had been noted.
      However, isolated bilateral mild pleural effusions were noted at 27 weeks of
      gestation. Amniocentesis revealed a karyotype of 47,XY,+21 and simultaneous array
      comparative genomic hybridization analysis of uncultured amniocytes confirmed the
      diagnosis of Down syndrome. The pregnancy was subsequently terminated.
      CONCLUSION: Fetuses with Down syndrome may present late-onset bilateral pleural
      effusions. Prenatal diagnosis of late-onset bilateral pleural effusions should
      raise the possibility of fetal Down syndrome and cytogenetic investigation is
      warranted.

PMID- 29458885
TI  - Prenatal diagnosis of fetal glutaric aciduria type 1 with rare compound
      heterozygous mutations in GCDH gene.
AB  - OBJECTIVE: Glutaric aciduria type 1 is a rare disease, with the estimated
      prevalence about 1 in 100,000 newborns. GCDH gene mutation can lead to glutaric
      acid and 3- OH glutaric acid accumulation, with clinical manifestation of
      neuronal damage, brain atrophy, microencephalic macrocephaly, decreased
      coordination of swallowing, poor muscle coordination, spasticity, and severe
      dystonic movement disorder. CASE REPORT: A 22-year-old female, Gravida 4 Para 2,
      is pregnancy at 13 weeks of gestational age. Her first child is normal, however,
      the second child was diagnosed as glutaric aciduria type I after birth. She came
      to our hospital for prenatal genetic counselling of her fetus at 13 weeks of
      gestational age. We performed GCDH gene mutation analysis of maternal blood
      showed IVS 3 + 1 G > A heterozygous mutation, GCDH gene mutation analysis of
      paternal blood showed c. 1240 G > A heterozygous mutation, and the second child
      has compound heterozygous IVS 3 + 1 G > A and c. 1240 G > A mutations. Later, we
      performed amniocentesis at 16 weeks of gestational age for chromosome study and
      GCDH gene mutation analysis for the fetus. The fetal chromosome study showed
      normal karyotype, however, GCDH gene mutation analysis showed compound
      heterozygous IVS 3 + 1 G > A and c. 1240 G > A mutations. The couple decided to
      termination of pregnancy thereafter. CONCLUSION: Glutaric acidemia type 1 is an
      autosomal recessive disorder because of pathogenic mutations in the GCDH gene.
      Early diagnosis and therapy of glutaric acidemia type 1 can reduce the risk of
      neuronal damage and acute dystonia. We report a case of prenatal diagnosis of
      fetal glutaric aciduria type 1 with rare compound heterozygous GCDH gene mutation
      at IVS 3 + 1 G > A and c. 1240 G > A mutations, which provide better genetic
      counselling for the couples.

PMID- 29458886
TI  - Laparoscopic en bloc resection of a para-cervical cancer with OHVIRA syndrome.
AB  - OBJECTIVE: There are some reports of cervical cancer with uterus didelphys but a
      case of clear cell carcinoma (CCCC) with Obstructed Hemivagina and Ipsilateral
      Renal Anomaly (OHVIRA) syndrome is extremely rare. The aim of this paper was to
      report a case of CCCC with OHVIRA syndrome and the difficulty in making a
      preoperative diagnosis. CASE REPORT: A 65 years old woman presented with
      postmenopausal bleeding and pelvic examination showed right paracervical mass.
      Preoperative confirmation of cervical carcinoma was difficult due to the location
      of the mass, which was inaccessible by cervical punch biopsy. Pelvic examination
      revealed a large mass in pelvic cavity without parametrial invasion and
      ultrasound showed approximately 70 mm cervical tumor. Laparoscopic surgery
      revealed clear cell carcinoma of the para-endocervix with OHVIRA syndrome.
      CONCLUSION: In the case of cervical carcinoma with OHVIRA syndrome, laparoscopic
      surgery is preferable for the diagnosis and management.

PMID- 29458887
TI  - Large cell neuroendocrine carcinoma of the endometrium: A case report and
      literature review.
AB  - OBJECTIVE: To report a case and review published cases of large cell
      neuroendocrine carcinoma (LCNEC) of the endometrium. CASE REPORT: A 51-year-old
      female presented with postmenopausal bleeding and a palpable pelvic mass. An
      endometrial biopsy showed a malignant mixed Mullerian tumor (MMMT). Suboptimal
      debulking surgery was performed. The final pathology revealed stage IVB
      endometrial LCNEC. Post-operative adjuvant chemotherapy with cisplatin and
      etoposide was administered. Two months after discontinuing adjuvant chemotherapy,
      salvage chemotherapy with cisplatin and ifosfamide was administered due to tumor
      progression; however, obstructive ileus was noted 2 months later. A segmental
      small bowel resection and palliative colostomy were performed. She died secondary
      to a post-operative infection 8 days after the operation. CONCLUSION: Endometrial
      LCNEC is a rare but aggressive disease. If diagnosed, combined therapies,
      including staging surgery, following by adjuvant radiotherapy and chemotherapy,
      should be performed.

PMID- 29458889
TI  - Pregnancy following robot-assisted laparoscopic partial cystectomy and
      gonadotropin-releasing hormone agonist treatment within three months in an
      infertile woman with bladder endometriosis.
AB  - OBJECTIVE: To report an infertility case of deep-infiltrating bladder
      endometriosis conceiving following robot-assisted surgery and modified
      gonadotropin-releasing hormone agonist (GnRHa) treatment. CASE REPORT: A 33 year
      old infertile female presenting with dysmenorrhea was found to have a bladder
      mass by pelvic ultrasound. Cystoscopy revealed a protruding tumor from the
      posterior bladder wall, and endometriosis was highly suspected. Robot-assisted
      laparoscopic partial cystectomy was performed for the deep-infiltrating bladder
      endometriosis. With postoperative half-dose GnRHa treatment and timed
      intercourse, she got pregnant within 3 months. CONCLUSION: Robot-assisted
      complete resection of deep-infiltrating endometriosis and bladder repair
      immediately followed by GnRHa therapy and medical assistance improves
      reproductive outcomes efficiently in women with endometriosis-associated
      infertility.

PMID- 29458888
TI  - Ureterovaginal fistula: A complication of a vaginal foreign body.
AB  - OBJECTIVE: To know the diagnostic tools and proper management of ureterovaginal
      fistula following neglected vaginal foreign body in order to achieve optimal
      outcome. CASE REPORT: A case of ureterovaginal fistula associated with a
      neglected vaginal foreign body. The patient was complaining of a foul-smelling
      vaginal discharge and lower abdominal pain. On vaginal examination, a hard and
      large foreign body was found. Examination under anesthesia was performed, and an
      aerosol cap was removed from her vagina. The patient developed urinary
      incontinence after removal of the foreign body. Subsequent work-up demonstrated
      the presence of a right ureterovaginal fistula. The patient underwent an
      abdominal ureteroneocystostomy. At one year follow up, the patient had fully
      recovered. CONCLUSION: Ureterovaginal fistula following neglected vaginal foreign
      body is a serious condition. Early diagnosis, treatment of infection and proper
      surgical management can improve the outcome and decrease complications.

PMID- 29458890
TI  - A vulvar mass as the first presentation in colorectal carcinoma: An unusual site
      of metastasis masquerading a primary cancer.
AB  - OBJECTIVE: To demonstrate a case with a vulvar metastasis masquerading a primary
      vulvar malignancy. The clinical and histological features, mechanism, and impact
      to the prognosis are discussed. CASE REPORT: A 58-year-old woman presented to
      gynecologist for abnormal vaginal discharge. A vulvar nodule was noticed during
      physical examination. Biopsy showed adenocarcinoma (ADC) and she was referred for
      further survey under the impression of Bartholin duct ADC. Later she was further
      found to also have a colorectal tumor with liver metastasis and subsequently
      received surgery under the suspicion of a double primary cancer involving the
      colon and vulva. The pathology revealed colorectal ADC with both hepatic and
      vulvar metastasis. CONCLUSION: Secondary tumor in female genital tract is unusual
      and vulvar metastasis is the rarest kind. The clinical manifestation may be
      perplexing especially if a patient is presented with a nonspecific gynecological
      symptom such as abnormal vaginal discharge without any past history.

PMID- 29458891
TI  - A large subchorionic placental cyst with thalassemia minor without fetal growth
      restriction.

PMID- 29458892
TI  - Prenatal diagnosis of tuberous sclerosis complex using fetal ultrasonography and
      magnetic resonance imaging and genetic testing.

PMID- 29458893
TI  - Diagnostic dilemma of long-retained vaginal foreign body: Value of MRI.

PMID- 29458894
TI  - An exceptional source of recurrent urinary tract infections in women: Primary
      retroperitoneal serous cystadenoma.

PMID- 29458895
TI  - Application of SIS (saline infusion sonohysterography) in diagnosis of perforated
      transverse vaginal septum.

PMID- 29458896
TI  - Comment on first trimester maternal serum analytes and second trimester uterine
      artery doppler in the prediction of preeclampsia and fetal growth restriction.

PMID- 29458897
TI  - Physical activities (exercises or choreses) during pregnancy and mode of delivery
      in nulliparous women: A prospective cohort study.
AB  - OBJECTIVE: The aim of this study was to investigate changes in physical
      activities during pregnancy and the relationship between physical activity and
      unplanned caesarean sections (CSs). MATERIALS AND METHODS: A cohort study design
      was carried out. A cohort of 2029 pregnant women was established when they
      received prenatal care at 18-22 weeks of gestation in a medical center in
      southwest Iran. Participants were asked to recall their levels of physical
      activity during pre-pregnancy. The data were processed using Statistics/Data
      Analysis. To compare activities the chi-square was used to identify significant
      differences between the groups. A multiple logistic regressian was used to
      identify the association between activities and delivery mode as well as
      controlling potential confounding variables. In the analyses, the level of
      significance was set at P < 0.05. RESULTS: In total, 2029 pregnant women
      participated in the study, among which 1334 (65.84%) underwent CSs and 692
      (34.16%) underwent NVDs. The study indicated the odds ratio of CS was 0.68 (95%
      CI: 0.47-0.97) for a pregnant woman who increased her level of activity during
      pregnancy compared to pre-pregnancy. CONCLUSION: The results of this study showed
      that regular and standard physical activities during pregnancy can reduce the
      risk of caesarean section in pregnant women. These findings can be important in
      convincing health care providers to prescribe regular and standard physical
      activities for pregnant women during pregnancy.

PMID- 29458898
TI  - Serum decorin measurement in prediction of the risk for preterm birth.
AB  - OBJECTIVE: To define serum decorin (sDEC) levels in healthy pregnants and in
      patients with preterm labor (PTL), and to introduce possible role of sDEC in
      predicting the risk for preterm birth (PTB). MATERIALS AND METHODS: Thirty-one
      women with diagnosis of PTL between 24th to 32nd weeks of pregnancy were compared
      with 44 healthy pregnants in this prospective case-control study. Maternal blood
      sDEC and uterine cervical length (CL) measurements were conducted at referral.
      RESULTS: Median sDEC level was significantly decreased in PTL group (p = 0.013).
      Median CL was significantly shorter in PTL group (p < 0.001). There was not any
      correlation between sDEC level and maternal age, BMI, and gestational age at
      blood sampling time within PTL (p = 0.955, p = 0.609, p = 0.079, respectively)
      and control groups (p = 0.652, p = 0.131, and p = 0.921, respectively). There was
      not any association between sDEC level and PTB within 7 days, before 34th weeks,
      but before 37th weeks there was (p = 0.206, 0.091, and p = 0.026, respectively).
      There was not any correlation between sDEC level and the CL in PTL group (p =
      0.056). CONCLUSIONS: sDEC has a limited effect in prediction of PTB within a week
      or before 34th weeks. Combination of sDEC with CL measurements predicted PTB
      before 37th weeks. CONCLUSION: 

PMID- 29458899
TI  - Single port access laparoscopic subtotal hysterectomy using contained manual
      morcellation: Experience from a tertiary referral center in Taiwan.
AB  - OBJECTIVE: To describe the surgical outcomes of single port access laparoscopic
      subtotal hysterectomy (LSH) using in-bag manual morcellation and evaluate the
      feasibility of this procedure. MATERIALS AND METHODS: Thirty patients with
      symptomatic leiomyoma or adenomyosis were enrolled. A 2-cm transverse incision
      was made at the umbilicus and single port apparatus (LagiPort) was applied. After
      dissection of vesicouterine peritoneum from the uterus, the uterine ligaments and
      vessels were secured and transected by Gyrus PK cutting forceps. Cervical
      amputation at the level of internal os was made by SupraLoop (Karl Storz). The
      uterine corpus was put into an Endobag before morcellation. The opening of
      Endobag was exteriorized from the umbilical incision and the uterine corpus was
      removed in a contained manner by manual morcellation with a scalpel. RESULTS:
      This procedure was successfully performed on all patients. Neither laparotomic
      conversion nor additional port was needed. The mean age and mean BMI of the
      patients were 43.63 years and 24.02 kg/?. The mean operative time was 148 min and
      the estimated blood loss in most patients was less than 150 ml. The median weight
      of uterine corpus was 214 g. No intraoperative complications occurred in any
      patient. One patient was diagnosed with unexpected endometrioid adenocarcinoma
      FIGO grade 1 postoperatively. One patient reported cyclic bleeding and underwent
      a transvaginal trachelectomy 17 months later. CONCLUSION: Single port access LSH
      using contained manual morcellation represents a safe and feasible alternative to
      conventional LSH using open power morcellation.

PMID- 29458900
TI  - Inter-observer variability in fetal biometric measurements.
AB  - OBJECTIVE: To evaluate inter-observer variability and reproducibility of
      ultrasound measurements for fetal biometric parameters. MATERIALS AND METHODS: A
      prospective cohort study was implemented in two tertiary care hospitals in Amman,
      Jordan; Prince Hamza Hospital and Albashir Hospital. 192 women with a singleton
      pregnancy at a gestational age of 18-36 weeks were the participants in the study.
      Transabdominal scans for fetal biometric parameter measurement were performed on
      study participants from the period of November 2014 to March 2015. Women who
      agreed to participate in the study were administered two ultrasound scans for
      head circumference, abdominal circumference and femur length. The correlation
      coefficient was calculated. Bland-Altman plots were used to analyze the degree of
      measurement agreement between observers. Limits of agreement +/- 2 SD for the
      differences in fetal biometry measurements in proportions of the mean of the
      measurements were derived. Main outcome measures examine the reproducibility of
      fetal biometric measurements by different observers. RESULTS: High inter-observer
      inter-class correlation coefficient (ICC) was found for femur length (0.990) and
      abdominal circumference (0.996) where Bland-Altman plots showed high degrees of
      agreement. The highest degrees of agreement were noted in the measurement of
      abdominal circumference followed by head circumference. The lowest degree of
      agreement was found for femur length measurement. We used a paired-sample t-test
      and found that the mean difference between duplicate measurements was not
      significant (P > 0.05). CONCLUSION: Biometric fetal parameter measurements may be
      reproducible by different operators in the clinical setting with similar results.
      Fetal head circumference, abdominal circumference and femur length were highly
      reproducible. Large organized studies are needed to ensure accurate fetal
      measurements due to the important clinical implications of inaccurate
      measurements.

PMID- 29458901
TI  - Characterization of tubo-ovarian abscess mimicking adnexal masses: Comparison
      between contrast-enhanced CT, 18F-FDG PET/CT and MRI.
AB  - : 0BJECTIVE: We compared the diagnostic accuracy of contrast-enhanced computed
      tomography (CT), fluorine 18-labeled-fludeoxyglucose (18F-FDG) positron emission
      tomography (PET)/CT and conventional magnetic resonance imaging (MRI) without and
      with diffusion-weighted imaging (DWI) for characterization of tubo-ovarian
      abscesses (TOAs) that mimic adnexal tumors. MATERIALS AND METHODS: We evaluated
      (retrospectively) 43 patients who underwent contrast-enhanced CT, PET/CT,
      conventional MRI without and with DWI, and who were found to have TOAs and
      complex adnexal tumors. All images were evaluated independently by four
      radiologists using a two-point grading system. Results of contrast-enhanced CT,
      PET/CT, MRI without DWI, and MRI with DWI were compared for each patient using
      receiver operating characteristic curves. Sensitivity, specificity, and positive
      predictive value (PPV) were calculated and compared using the chi-square test.
      RESULTS: Sensitivity of MRI with DWI (95%) was significantly higher than that of
      contrast-enhanced CT (78.6%), PET/CT (86.7%) and MRI without DWI (87.5%).
      Specificities of these modalities were not significantly different. The PPV of
      MRI with DWI (100%) was significantly higher than that of the other three
      modalities (CT, 72.4%; PET/CT 78.5%; MRI without DWI, 81.5%). Overall accuracy of
      MRI with DWI was significantly higher than that of the other three modalities
      (CT, 74.4%; PET/CT, 81.4%; MRI without DWI, 83.7%). CONCLUSION: MRI with DWI
      shows high accuracy for characterization of complex ovarian lesions, and is the
      most useful method for differentiation of TOAs from ovarian tumors.

PMID- 29458902
TI  - Postoperative maintenance levonorgestrel-releasing intrauterine system for
      symptomatic uterine adenomyoma.
AB  - OBJECTIVE: To evaluate whether a maintenance levonorgestrel-releasing
      intrauterine system is effective for preventing the recurrence of postoperative
      adenomyosis-related symptoms. MATERIALS AND METHODS: From January 2005 through
      December 2014, a retrospective study including 133 patients with symptomatic
      adenomyosis undergoing conservative uterine-sparing surgery followed by
      gonadotropin-releasing hormone agonist treatment was conducted. We excluded the
      18 patients who did not meet the inclusion criteria. The patients of intervention
      group (n = 54) received a levonorgestrel-releasing intrauterine system (LNG-IUS),
      which was inserted after surgery. The patients without LNG-IUS insertion were
      enrolled in the control group (n = 61). The primary outcome was improvement of
      adenomyosis-related dysmenorrhea, which was evaluated by the visual analog scale
      (VAS) and by hemoglobin (Hgb) and CA-125 levels. RESULTS: Over a 12-month follow
      up, the intervention group exhibited a greater reduction in dysmenorrhea as
      assessed with a VAS score (mean +/- SD: 6.5 +/- 2.5 vs 4.1 +/- 3.6, p = 0.001)
      and a greater elevation in the Hgb level (2.1 +/- 1.9 vs 1.0 +/- 1.7, p = 0.008)
      than the control group. At the end of the 24-month follow-up period, the
      intervention group also exhibited a greater reduction in dysmenorrhea as assessed
      with a VAS score (mean +/- SD 6.1 +/- 2.7 vs 3.7 +/- 3.7, p = 0.002) and a
      greater elevation in the Hgb level (1.9 +/- 2.1 vs 0.7 +/- 1.8, p = 0.022) than
      the control group. The CA-125 level was significantly lower in the intervention
      group during the postoperative follow up (12th month follow-up, intervention vs
      control, 24.5 +/- 28.8 vs 50.1 +/- 44.0, p = 0.005; 24th month follow-up, 28.6 +/
      26.2 vs 75.4 +/- 68.5, p = 0.002). CONCLUSION: The maintenance therapy of LNG
      IUS is effective and well accepted for long-term therapy after conservative
      surgery for patients with adenomyosis.

PMID- 29458903
TI  - Day 4 good morula embryo transfer provided compatible live birth rate with day 5
      blastocyst embryo in fresh IVF/ET cycles.
AB  - OBJECTIVE: Embryo transfers during cleavage stage (day 2 or day 3) and blastocyst
      stages (day 5 or day 6) are common in current daily practice in fresh IVF/ET
      cycles. Data regarding transferring day 4 embryos, morula/compact stage, is still
      restricted and the grading system is also inconsistent, as between IVF clinics.
      This study provided a new detailed classification system for morula/compact stage
      embryos and compared successes rates between day 4 and day 5 ET. MATERIALS AND
      METHODS: This was a retrospective study. A review of medical records from January
      1st, 2013, to December 31st 2015, performed for all conventional insemination and
      ICSI cycles with a GnRH-antagonist protocol at the Infertility Division of MacKay
      Memorial Hospital in Taipei City, Taiwan. RESULTS: There were 427 cycles included
      in our study, 107 in study group (day 4 MET) and 320 in control group (day 5
      BET). Pregnancy rates and live birth rate were compatible, as between morula
      embryo transfer (MET) and blastocyst embryo transfer (BET). The implantation rate
      (36.3% vs. 39.6%, respectively, p = 0.500), clinical pregnancy rate (49.5% vs.
      51.9%, respectively, p = 0.737), and live birth rate (42.1% vs. 45.6%,
      respectively, p = 0.574) were statistically insignificant between groups. The
      term birth rate was statistically higher in the MET group than in the BET group
      (95.7% vs. 79.5%, respectively, p = 0.006). When the clinical outcomes between
      day 4 good MET and day 5 good BET were compared, the results were compatible. The
      implantation rate (48.8% vs. 41.1%, respectively, p = 0.335), clinical pregnancy
      rate (55.0% vs. 53.2%, respectively, p = 0.867), and live birth rate (47.5% vs.
      47.1%, respectively, p = 1.000) showed no significant difference. The term birth
      rate was also higher in day 4 good MET group than in day 5 good BET group (100%
      vs. 78.3%, respectively, p = 0.025). CONCLUSION: In this study, we performed day
      4 MET avoid BET on Sunday. The grading system we provided was more detailed for
      embryo selection and it was easier to remember. Our data showed that morula
      embryo transfer might be a flexible, easier and applicable method for embryo
      transfer in daily routine.

PMID- 29458904
TI  - Serum vitamin D concentrations in young Turkish women with primary dysmenorrhea:
      A randomized controlled study.
AB  - OBJECTIVE: This study aims to investigate the possible role of vitamin D
      deficiency in primary dysmenorrhea by assessing serum 25-hydroxyvitamin D3 levels
      in a cohort which includes young Turkish women with primary dysmenorrhea and
      healthy controls. MATERIALS AND METHODS: A total of 683 women who were aged
      between 18 and 25 years and who were consecutively admitted to the study center
      were eligible. After the exclusion of 55 women, 184 women with primary
      dysmenorrhea were randomly assigned into the dysmenorrhea group and 184 women
      without dysmenorrhea were randomly allocated into the control group. RESULTS: The
      dysmenorrhea group had significantly less consumption of dairy products (p =
      0.001), lower serum calcium (p = 0.001), lower serum vitamin D (p = 0.001) and
      higher serum parathyroid hormone (p = 0.001) than those of the control group.
      Hyperparathyroidism was significantly less frequent whereas vitamin D deficiency
      was significantly more frequent in the dysmenorrhea group (p = 0.001 for each).
      The dysmenorrhea patients with vitamin D deficiency had significantly higher
      visual analogue scale (VAS) scores (p = 0.001). Depression, irritability, mood
      swings, fatigue, headache and breast tenderness were significantly more frequent
      in the vitamin D deficiency group (p < 0.05 for all). The VAS scores of the
      dysmenorrhea patients correlated positively and significantly with serum
      parathyroid hormone levels (r = 0.666, p = 0.001) whereas these VAS scores
      correlated negatively and significantly with serum vitamin D levels (r = -0.713,
      p = 0.001). DISCUSSION: The significant and positive correlation between vitamin
      D levels and VAS scores and the significant reduction in serum vitamin D levels
      of the dysmenorrhea patients designate the possible role of vitamin D deficiency
      in the primary dysmenorrhea.

PMID- 29458905
TI  - Obstetric outcomes of twin pregnancies at advanced maternal age: A retrospective
      study.
AB  - OBJECTIVE: To evaluate obstetric outcomes in twin pregnancies of advanced
      maternal age (>=35 years). MATERIALS AND METHODS: A retrospective study involved
      470 twin pregnancies in a single center from Sep. 1, 2012 to Mar. 31, 2015.
      Clinical characteristics and obstetric outcomes were recorded and compared among
      twin pregnancies who were classified as follows: age 20-29, 30-34, 35-39 and >=40
      years. RESULTS: The incidence of gestational diabetes (age 20-29 years 15.8%; 30
      34 years 24.3%; 35-39 years 30.4%; >=40 years 57.1%; p = 0.004) and premature
      delivery (20-29 years 58.6%; 30-34 years 69.1%; 35-39 years 72.2%; >=40 years
      85.7%; p = 0.001) significantly increased with increasing age whereas spontaneous
      abortion (20-29 years 27.6%; 30-34 years 11.6%; 35-39 years 11.4%; >=40 years
      0.0%; p = 0.021) decreased in twin pregnancies of advanced maternal age. In
      addition, the rate of postpartum hemorrhage increased almost continuously by age
      and advanced maternal age was described as a risk factor for postpartum
      hemorrhage (age 35-39, adjusted OR 3.377; 95% confidence interval 1729-6.598; p <
      0.001; age >= 40, adjusted OR 10.520; 95% CI 1.147-96.492; p = 0.037). However,
      there was no significant difference between advanced maternal age and adverse
      neonatal outcomes. CONCLUSION: In twin pregnancies, advanced maternal age
      experienced significant higher risk of postpartum hemorrhage, gestational
      diabetes and premature delivery. Neither adverse neonatal outcomes nor stillbirth
      was significantly associated with maternal age.

PMID- 29458906
TI  - Comparative cosmetic outcome of surgical incisions created by the PEAK Plasma
      Blade and a scalpel after cesarean section by Patient and Observer Assessment
      Scale (POSAS): A randomized double blind study.
AB  - OBJECTIVE: To compare the cosmetic result of the PEAK Plasma Blade with
      traditional scalpel in patients who had primary cesarean delivery by using POSAS
      (Patient and Observer Assessment Scale). MATERIAL AND METHODS: Fourty women
      between 20 and 40 years, who were planning to have primary cesarean delivery,
      were randomized for skin incision with PEAK Plasma Blade (n:20) and with scalpel
      (n:20) were blinded to their group allocation. At six months, the cosmetic
      outcome of the cesarean scar was assessed using the POSAS. Subjective scar rating
      was performed using the patient component of the POSAS. Objective scar assessment
      was performed by an observer dermatologist blinded to the patient's group
      allocation. RESULTS: The observer scores (p = 0,003), patient scores (p = 0,001)
      and the total scores (p = 0,001) of the POSAS scale were significantly lower in
      favor of the Peak Plasma Blade group with respect to the scalpel group.
      CONCLUSION: The PEAK Plasma Blade has superior cosmetic outcome compared to
      traditional scalpel skin incision at cesarean section.

PMID- 29458907
TI  - Surgical and survival outcomes of laparoscopic staging surgery for patients with
      stage I ovarian cancer.
AB  - OBJECTIVE: To assess the feasibility and survival outcomes of laparoscopic
      staging for patients with stage I ovarian cancer. MATERIALS AND METHODS:
      Consecutive patients who underwent laparoscopic staging surgery for stage I
      ovarian cancer from January 2002 to December 2014 were evaluated retrospectively
      by chart review. RESULTS: Twenty-four patients with mean age 43.9 +/- 9.9 years
      and mean body mass index 24.0 +/- 3.8 kg/m2 were included, in which 12 (50%)
      patients were in stage IA and 12 (50%) in stage IC. The histological types
      included serous in 6 (25%), mucinous in 7 (29.1%), endometrioid in 6 (25%), clear
      cell in 5 (20.8%) patients. The mean surgical time was 306.4 +/- 98.5 min, and
      the mean blood loss was 204.2 +/- 188.6 mL. None of the patients required
      conversion to laparotomy. The median numbers of resected pelvic and para-aortic
      lymph nodes were 20 and 4, respectively. One (4.1%) patient encountered bowel
      injury intraoperatively, and the other 1 (4.1%) patient hydronephrosis
      postoperatively. The overall survival rate was 95% in the current series in a
      median follow-up of 31.5 months. CONCLUSION: Laparoscopic staging surgery
      performed for early stage ovarian cancer has better long term survival outcomes
      than the literature report. Laparoscopic treatment by a trained gynecologic
      oncologist is an ideal alternative for early stage ovarian cancer with the
      advantage of minimal invasiveness.

PMID- 29458908
TI  - Is pregnancy associated plasma protein-A (PAPP-A) a marker for adverse perinatal
      outcomes in preterm isolated oligohydramnios cases?
AB  - OBJECTIVE: Isolated oligohydramnios is defined as an amniotic fluid index below
      five centimeter with no other coexisting condition. There are still controversies
      about the management and pregnancy outcomes. A marker predicting these is
      crucial. Low pregnancy associated plasma protein-A levels were reported to be
      related with adverse pregnancy outcomes. We aimed to determine the role of first
      trimester pregnancy associated plasma protein-A for poor outcomes in preterm
      isolated oligohydramnios cases. MATERIAL AND METHODS: Fifty-one patients with
      singleton pregnancies diagnosed as isolated oligohydramnios at 28/0-36/6 weeks of
      gestation and 110 gestational age matched healthy controls between January and
      December 2015 were included. Maternal age, gestational age at delivery, mode of
      delivery, indication for cesarean section, Apgar scores at first and fifth
      minutes, birth weight, neonatal intensive care unit admission and mortality were
      recorded. Pregnancy associated plasma protein-A levels were compared between
      groups and its role in adverse perinatal outcomes was evaluated. RESULTS:
      Pregnancy associated plasma protein-A levels and pregnancy outcomes were similar
      in two groups (p > 0.050) except birth weight, gestational age at delivery and
      presence of fetal distress. Pregnancy associated plasma protein-A levels did not
      differ in terms of delivery mode, presence of fetal distress, first and fifth
      minutes Apgar scores and neonatal intensive care unit admission (p =
      0.323,0.650,0.990,0.112,0.853). Also, it was not determined as a risk factor for
      cesarean section, presence of fetal distress, low Apgar scores and neonatal
      intensive care unit admission. CONCLUSION: Pregnancy associated plasma protein-A,
      a well-known prognostic factor for some of high risk pregnancy conditions, may
      not be used as a marker in preterm isolated oligohydramnios cases.

PMID- 29458909
TI  - Effect of morphokinetics and morphological dynamics of cleavage stage on embryo
      developmental potential: A time-lapse study.
AB  - OBJECTIVE: Using a non-invasive method to select the most competent embryo is
      essential in in vitro fertilization (IVF). Since the beginning of clinical
      application of time-lapse technology, several studies have proposed models using
      the time-lapse imaging system for predicting the IVF outcome. This study used
      both morphokinetic and morphological dynamic parameters to select embryos with
      the highest developmental potential. MATERIALS AND METHODS: A total of 23
      intracytoplasmic sperm injection treatment cycles with 138 fertilized oocytes
      were included in this study. All embryos were cultured to the blastocyst stage,
      and embryo development was recorded every 10 min by using a time-lapse imaging
      system. Morphokinetic parameters and eight major abnormal division behaviors were
      studied to determine their effects on blastocyst formation. The most influential
      variables were used in hierarchical classification for blastocyst formation
      prediction. RESULTS: Several parameters were significantly related to the
      developmental potential. Embryos with the timing of pronuclear fading (tPNF) of
      >26.4 h post insemination (hpi), the timing of division to two cells (t2) of
      >29.1 hpi, and the timing of division to four cells (t4) of >41.3 hpi showed the
      lowest blastocyst formation rate. The abnormal division behaviors of
      fragmentation >50%, direct cleavage, reverse cleavage, and delayed division or
      developmental arrest were found to be detrimental to blastocyst formation. On the
      basis of these results, we propose a hierarchical model classification, in which
      embryos are classified into groups A-D according to their developmental
      potential. The blastocyst formation rates of groups A, B, C, and D were 80.0%,
      77.8%, 53.7%, and 22.2% (p < 0.001). The good blastocyst rates of groups A, B, C,
      and D were 60.0%, 44.4%, 14.6%, and 11.1% (p = 0.007). CONCLUSION: We propose a
      hierarchical classification system for blastocyst formation prediction, which
      provides information for embryo selection by using a time-lapse imaging system.

PMID- 29458910
TI  - Maternal characteristics and pregnancy outcomes among illicit drug-using women in
      an urban setting.
AB  - OBJECTIVE: To identify characteristics and pregnancy outcomes among pregnant
      illicit drug users living in an urban area, and to describe trends in drug use
      over an 8-year period. MATERIALS AND METHODS: Data on pregnant women living in
      the Bangkok Metropolitan Region who delivered at our institution during 2008-2015
      were studied. Women with drug use (n = 197) and women without drug use (n = 787)
      were compared in terms of maternal characteristics and pregnancy outcomes.
      RESULTS: The pregnant drug user rate markedly rose from 0.46% in 2008 to 1.28% in
      2015. All pregnant drug users consumed amphetamine-type stimulants (ATS). The
      most important factor related to drug use was smoking (adjusted odds ratio [aOR]
      41.03, 95% confidence interval [CI] 18.90-89.04). Other significant
      characteristics were teenage pregnancy (aOR 1.78, 95% CI 1.01-3.18), low level of
      education (aOR 4.97, 95% CI 1.18-20.90 for secondary school and aOR 5.61, 95% CI
      1.28-24.49 for primary school or lower), and inadequate number of antenatal
      visits (aOR 2.20, 95% CI 1.16-4.17 for 1-3 visits and aOR 14.05, 95% CI 7.54
      26.16 for no visit). Women of non-Thai ethnicity were less likely to use drugs
      (aOR 0.15, 95% CI 0.04-0.54). Pregnant drug users had a significantly higher risk
      of anemia (aOR 1.73, 95% CI 1.05-2.85), preterm delivery (aOR 2.35, 95% CI 1.29
      4.29), low birth weight (aOR 2.26, 95% CI 1.23-4.17) and small for gestational
      age infants (aOR 3.19, 95% CI 1.39-7.33), but lower risk of cesarean section (aOR
      0.43, 95% CI 0.21-0.86) than non-drug users. CONCLUSION: Compared to urban
      pregnant women without drug use, women who consumed drugs were younger, had lower
      level of education, poorer self-care and poorer pregnancy outcomes. ATS was the
      single most commonly used drug.

PMID- 29458911
TI  - Pharmacogenetic study of pruritus induced by epidural morphine for post cesarean
      section analgesia.
AB  - OBJECTIVE: The mechanism through which neuroaxial morphine causes pruritus has
      not been elucidated clearly and thoroughly. MATERIALS AND METHODS: a study in 129
      female parturients was conducted to investigate the effect of 14 single
      nucleotide polymorphisms (SNPs) on phenotype (pruritus) induced by neuroaxial
      (including intrathecal or epidural) morphine for cesarean section. Clinical
      phenotype, subjective complaints and objective observations were recorded. DNA
      from blood samples was used to record the SNPs. Eleven SNPs were then analyzed
      further. RESULTS: no significant association with the presence of phenotype
      (pruritus) versus genotype was observed (all p-values > 0.05). No significant
      association with severity of phenotype versus genotype of the 11 SNPs was
      observed except for unadjusted data for rs2737703. There was no significant
      difference between severity or incidence of IVPCA morphine-induced nausea and
      vomiting and genotype (11 SNPs). CONCLUSION: our results showed no association
      between SNPs of any of the genes studied with neuroaxial morphine inducing
      pruritus.

PMID- 29458912
TI  - Early fetal reduction to twin versus prophylactic cervical cerclage for triplet
      pregnancies conceived with assisted reproductive techniques.
AB  - OBJECTIVE: To compare the obstetric outcomes of triplet gestations managed by
      early fetal reduction to twins with those managed by prophylactic cervical
      cerclage in women conceived with assisted reproductive techniques (ART).
      MATERIALS AND METHODS: Retrospective study of the pregnancy and neonatal outcomes
      of trichorionic triplet gestations achieved by ART and managed either by early
      transvaginal fetal reduction to twins (n = 53) or by prophylactic placement of
      cervical cerclage (n = 65). RESULTS: The pregnancy duration was significantly
      longer with fetal reduction and the incidences of delivery before 34 and 32 weeks
      gestational age were significantly lower with fetal reduction. Both miscarriage
      and live birth rates were comparable in the two groups. The incidences of very
      low birth weight (VLBW), neonatal respiratory distress syndrome (RDS), admission
      to neonatal intensive care unit (NICU) and early neonatal death (END) were
      significantly lower with fetal reduction. CONCLUSION: Early transvaginal
      reduction of triplets to twins leads to improved obstetric outcomes as it
      decreases prematurity and its related neonatal morbidities and mortality without
      increase in the miscarriage rate. Early fetal reduction seems to be better than
      continuation of triplet pregnancies with prophylactic placement of cervical
      cerclage.

PMID- 29458913
TI  - Use of complementary approaches in pregnant women with a history of miscarriage.
AB  - OBJECTIVES: To describe the use of complementary approaches in pregnant women
      with a history of miscarriage and to investigate whether a miscarriage is
      associated with the use of complementary approaches during their pregnancy.
      DESIGN: A cross-sectional survey was distributed to pregnant women residing in
      the United States (N=890). RESULTS: Women who had a history of miscarriage, were
      Caucasian, were college educated, reported a high income, had low depression
      scores, and had low anxiety scores (all P<0.001) were more likely to use
      complementary approaches. In pregnant women with a history of miscarriage
      (N=193), the most frequently reported complementary approaches used were prayer
      (22.3%), yoga (15%), massage (14.5%), chiropractic (13%), and meditation (11.4%).
      Finally, after adjustment for age, race, education, and income, the odds of using
      a complementary approach in women with a history of miscarriage was 1.8 (95% CI:
      1.3, 2.5, P<0.001) as compared with women without a history of miscarriage (model
      1). Associations persisted after additional adjustment for depression, anxiety,
      and stress; the odds of using a complementary approach in women with a history of
      miscarriage was 1.7 (95% CI: 1.2, 2.4, P<0.001) (model 2), compared with women
      without a history of miscarriage. CONCLUSIONS: Findings from this study may help
      inform future studies for pregnant women with a history of miscarriage and may
      also provide information about appropriate strategies in which health care
      providers can refer their patients.

PMID- 29458914
TI  - Associations between complementary medicine, satisfaction with body weight and
      shape, and the use of methods to lose or control weight: Results of a national
      survey of 8009 Australian women.
AB  - OBJECTIVE: This study aimed to determine whether the use of complementary
      medicine (CM) is associated with body satisfaction and weight management methods
      in Australian women. METHODS: Women aged 34-39 years from the Australian
      Longitudinal Study on Women's Health were surveyed regarding satisfaction with
      their body weight and shape, and the use of weight management methods.
      Associations with CM use were analysed using logistic regression modelling.
      RESULTS: Women using CM less likely wanted to lose weight; and were more likely
      to cut down on fats and/or sugars, use low glycaemic diets, diet books and
      'other' methods (OR: 1.33-2.83) compared to CM non-users. Women using herbal
      medicine products 'sometimes' were more likely to use meal replacements/slimming
      products (OR: 1.50-1.67) compared to non-users. DISCUSSION: Australian women
      using CM are more likely to be satisfied with their body weight and shape, and to
      use a range of weight management approaches compared to CM non-users.

PMID- 29458915
TI  - The effects of reflexology on anxiety and pain in patients after abdominal
      hysterectomy: A randomised controlled trial.
AB  - OBJECTIVES: This study aimed at finding out the effects of reflexology on pain,
      anxiety levels after abdominal hysterectomy. DESING & METHODS: The study was
      performed on women hospitalized in the intensive care unit and gynecology
      services of Ege University Hospital in Izmir after abdominal hysterectomy between
      September 2013 and September 2014. This study was designed and conducted as a
      randomized controlled trial. The study sample consisted of 63 female patients: 32
      in the experimental group and 31 in the control group. The postoperative daily
      monitoring sheet, Spielberger State Anxiety Inventory (SAI), was employed to
      collect research data and "visual analog scale" to evaluate pain levels. RESULTS:
      The female patients' average age was found to be 47.23 +/- 4.71. The three-day
      monitoring showed a significant difference between the experimental and control
      groups in terms of average pain levels and anxiety scores after reflexology (p <
      0.05). CONCLUSION: Foot reflexology may serve as an effective nursing
      intervention to increase the well-being and decrease the pain of female patients
      after abdominal hysterectomy, and nurses should be aware of the benefits of
      reflexology.

PMID- 29458916
TI  - Use of complementary and alternative medicine in patients with multiple sclerosis
      in Germany.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) for chronic
      diseases such as multiple sclerosis (MS) is becoming an increasingly important
      issue for those affected. Especially in Germany there are only a few studies
      dealing with CAM, as yet. The aim of this study was to assess the prevalence, the
      methods used, the subjective benefits as well as physician/patient communication.
      METHODS: A structured questionnaire including demographic and disease-specific
      data, CAM use, perceived benefits as well as physician/patient communication was
      sent to real and web-based self-help groups for MS in Germany. RESULTS: 343
      answers could be evaluated. 77.3% of the participants were females. The mean age
      was 45.0 +/- 11.9 years and the duration of the disease was 12.0 +/- 9.6 years.
      81.9% said they were using CAM, nearly half (44.8%) used it alternatively to
      conventional medicine. The average number of CAM- methods used were 3.6. The most
      popular methods were vitamin supplements, Yoga/Thai chi/Qi Gong, relaxation
      techniques and meditation. Approximately half (139/49.5%) of CAM users disclosed
      this to their treating neurologist. Yet, 37,6% have doubts on the competence of
      the respective physician. CONCLUSION: Patients with MS have a strong interest in
      CAM. Usage as alternative therapy is widespread and puts patients at risk of
      progress of the disease. As patient/physician communication on the topic is
      increasing, neurologists should be attentive to guiding their patients through
      safe complementary methods.

PMID- 29458917
TI  - Chinese herbal medicine to treat urolithiasis in a patient with right flank pain
      and hematuria: A case report.
AB  - OBJECTIVE: Urolithiasis is a common medical condition affecting the urinary
      tract. Typical symptoms reported by patients include colic pain and hematuria.
      Some patients may undergo surgical intervention or lithotripsy to remove the
      stones. In this case, we demonstrated that Chinese herbal medicine (CHM) was an
      effective modality to remove stones in a patient with urolithiasis. CLINICAL
      FEATURES AND OUTCOME: A 47-year-old man suffered from right flank pain and
      hematuria for three months and was diagnosed with an upper third ureteral stone
      obstruction with right hydronephrosis. He had received extracorporeal shock wave
      lithotripsy (ESWL) three times before his first CHM visit, but it was
      unsuccessful. Therefore, he sought CHM for further intervention. His symptoms
      subsided, and the image study showed complete removal of the ureteral stone after
      regular therapy with Zhi Bai Di Huang Wan () combined with Lygodii spora (),
      Curcumae radix (), Endothelium Corneum Gigeriae Galli (), Lysimachiae herba (),
      Orthosiphon stamineus () for approximately four months. Neither complications nor
      side-effects were noted during the CHM treatment. CONCLUSIONS: In this case, we
      concluded that CHM may be an effective alternative therapy for the treatment of
      ureteral stones, and furthermore, may also be applied as an option to salvage
      failed ESWL procedures.

PMID- 29458918
TI  - Management of IFN-beta-induced flu-like symptoms with Chinese herbal medicine in
      a patient with multiple sclerosis: A case report.
AB  - OBJECTIVE: The purpose of this case report was to elucidate how Chinese herbal
      medicine (CHM) was used safely in this patient undergoing interferon beta
      (IFNbeta-1a) treatment and was associated with reduction in the side effects the
      patient had experienced when using IFNbeta-1a treatment alone. CLINICAL FEATURES
      AND OUTCOME: A 30-year-old man was diagnosed with MS in December 2014. For two
      years, he suffered from severe flu-like symptoms as side effects of IFNbeta-1a
      treatment. He subsequently received treatment with Chinese herbal medicine.
      During a two-month period of treatment with CHM, the patient responded well, with
      most of the symptoms induced by IFNbeta-1a ameliorated. The fever subsided.
      Incidence rates of dizziness and headaches were reduced. The health condition
      compared to the prior year increased by 50%. According to CCMQ and SF-36
      assessments, CHM had the beneficial effects of recovering the yin-yang balance,
      harmonizing the qi, and regulating the blood state; essentially, improving the
      patient's comfort level and quality of life. CONCLUSIONS: IFNbeta-1a injections
      will damage qi and cause blood stasis in MS patients, thereby causing various
      side effects and weakening the body's immune system. Bu-Zhong-Yi-Qi-Tang,
      associated with Salvia miltiorrhiza, Ligusticum chuanxiong, Angelica dahurica and
      Polygonum multiflorum Thunb., is an effective prescription to ameliorate such
      symptoms and signs in patients with MS.

PMID- 29458919
TI  - Yoga meditation (YoMed) and its effect on proprioception and balance function in
      elders who have fallen: A randomized control study.
AB  - OBJECTIVE: Yoga has been shown to improve muscle strength, flexibility, and
      balance. However, the impact of meditation on dynamic factors such as gait,
      reactive balance and proprioception has yet to be examined. The purpose of this
      study was to test if a novel yoga meditation program (YoMed) is as effective as a
      standard proprioceptive training in improving proprioception, balance and power
      in older individuals who have fallen. DESIGN: Sixteen older persons were randomly
      assigned to either the YoMed Group (YM) or Proprioception Training Group (PT).
      Each group received 45 min of training, 3 days per week, for 6 weeks. Pretest and
      post-test outcome measures were used to quantify the comparative effects of the
      interventions. SETTING: Research Laboratory. INTERVENTIONS: Yoga meditation and
      proprioceptive training. MAIN OUTCOME MEASURES: The Balance Error Scoring System
      (BESS), the Tenetti Balance and Gait Assessment, dynamic posturography, joint
      position sense, joint kinesthesia and leg extensor power. RESULTS: The primary
      findings of the study were that neither the YM or PT intervention groups showed
      statistical improvements in any variable with the exception of the dynamic
      posturography overall score (DMA), which showed a significant improvement by the
      YM group (d = 1.238; p = 0.049). Additionally changes in a number of variables
      that did not reach significance demonstrated effect sizes in the medium to high
      range. CONCLUSION: These results indicate the potential for the YoMed program to
      be used as a clinical intervention in older individuals. Given these results a
      longer study using a larger sample size and individuals at higher risk of falling
      is warranted.

PMID- 29458920
TI  - Interest in online interprofessional elective mind-body skills (MBS) training.
AB  - INTRODUCTION: There is growing interest in mind-body skills (MBS) education and
      online interprofessional elective MBS training for health professionals. We
      conducted this study to understand a) the demand among different health
      professionals for an online MBS course; b) engagement with different MBS topics;
      and c) planned behavior changes. METHODS: We examined registrations from May 1
      through August 31, 2014 for a new online MBS elective, analyzing the percentage
      of registrants who engaged with one or more of 12 modules by September 30, 2014.
      We also reviewed written comments about planned behavior change. RESULTS: The 693
      registrants included physicians, nurses, social workers, dietitians,
      psychologists, and others. The two most popular topics were "Introduction: to
      Stress, Resilience, and Relaxation Response" and "Autogenic Training". Half of
      registrants (57%) engaged with at least one module and 9% completed all 12
      modules within the study period. Nearly all (90%) of those who completed
      evaluations planned to use the technique they learned for themselves, introduce
      it to patients, or both. DISCUSSION: Online elective MBS training attracts
      diverse health professionals and leads to plans for personal and professional
      behavior change. Additional research is necessary to understand the impact of
      different amounts and kinds of MBS training on professionals' resilience,
      burnout, and quality of care.

PMID- 29458921
TI  - Plasma metabolic profiling on postoperative colorectal cancer patients with
      different traditional Chinese medicine syndromes.
AB  - OBJECTIVES: This study aims to investigate the metabolic profiles of
      postoperative colorectal cancer (PCRC) patients with different traditional
      Chinese medicine (TCM) syndromes and to discuss the metabolic mechanism under
      PCRC progression and TCM syndrome classification. METHODS: Fifty healthy controls
      (HC) and 70 PCRC patients, including 10 Dampness and heat syndrome (DHS), 33
      Spleen deficiency syndrome (SDS), 19 Liver and kidney Yin deficiency syndrome
      (LKYDS) and 8 with non-TCM syndrome (NS) were enrolled. Plasma metabolic profiles
      were detected by Gas chromatography-mass spectrometry (GC-MS) and analyzed by
      principal component analysis (PCA) and partial least squares-discriminate
      analysis (PLS-DA). Furthermore, pathway enrichment was analyzed based on KEGG and
      DAVID databases and metabolic network was constructed via metaboanalyst and
      cytoscape. RESULTS: The top-3 metabolites with higher abundance in PCRC compared
      with HC were terephthalic acid (165.417-fold), ornithine (24.484-fold) and
      aminomalonic acid (21.346-fold). And the cholesterol (0.588-fold) level was
      decreased in PCRC. l-Alanine, 1, 2-ethanediamine, urea, glycerol, glycine,
      aminomalonic acid, creatinine and palmitic acid were specifically altered in the
      DHS, while d-tryptophan was exclusively changed in SDS, and l-proline, 1, 2, 3
      propanetricarboxylic acid, d-galactose and 2-indolecarboxylic acids in LKYDS.
      CONCLUSIONS: The plasma metabolic profiles were perturbed in PCRC patients.
      Increased levels of terephthalic acid might indicate high risk of relapse and
      elevated ornithine may contribute to the post-operational recovery or may raise
      the susceptibility to PCRC recurrence. The metabolic profiles of DHS, SDS, LKYDS
      and NS were almost separately clustered, indicating the possibility of explaining
      TCM syndromes classification using metabolomics. Furthermore, creatinine and
      aminomalonic acid alternation might correlate with the formation of DHS, while d
      tryptophan may associate with SDS and d-galactose and 1, 2, 3
      propanetricarboxylic acid may relate to LKYDS. As numbers of patients in each TCM
      syndrome are small, further study is needed to verify those results.

PMID- 29458922
TI  - Massage therapy for home care patients using the health insurance system in
      Japan.
AB  - OBJECTIVES: To clarify the status of home care massage services provided to
      patients. This will help in understanding how many patients utilize this service
      and the circumstances under which treatment is provided. DESIGN: A retrospective
      study. SETTING: Fifty-four acupuncture, moxibustion, and massage clinics.
      Participants were patients who had received home care massage for six months or
      more. We collected a total of 1587 responses from these 54 massage clinics; of
      these, 1415 responses (mean age = 79.1 +/- 11.5 years) were valid (valid response
      rate 89.2%). MAIN OUTCOME MEASURES: Actual patients and actual care services.
      RESULTS: The most common disorder observed among patients who utilized home care
      massage services was cerebrovascular disease (at approximately 36%), while the
      second most common were arthropathy-related disorders (16.3%). Although most
      patients received massage, approximately 30% received manual therapy (e.g. manual
      correction) and hot fomentation as part of thermotherapy. Notably, only around
      10% of patients received massage alone; the majority received treatment in
      combination with range of motion and muscle-strengthening exercises. CONCLUSIONS:
      This study helped to clarify the actual state of patients receiving home care
      massage and the details of the massage services provided. This study clearly
      showed the treatment effectiveness of massage, which can be used by home medical
      care stakeholders to develop more effective interventions.

PMID- 29458923
TI  - A bicentric controlled study on the effects of aquatic Ai Chi in Parkinson
      disease.
AB  - OBJECTIVES: Various exercise strategies have been suggested to address movement
      deficits in order to improve motor function and quality of life for individuals
      in the early or moderate stages of Parkinson disease. The purpose is to evaluate
      the effects of an aquatic Ai Chi intervention on balance, gait speed and quality
      of life of patients. DESIGN AND INTERVENTION: Twenty-nine people with Parkinson
      disease participated in this pilot study. People were randomized into (1) aquatic
      Ai Chi program (experimental group) and (2) a dry land conventional Western
      physical therapy intervention (control group). Twenty-two twice-weekly sessions
      were performed with the 14 patients assigned to the experimental group, during
      the same period of time as the control group (same number of sessions), who
      received dry land therapy. MAIN OUTCOMES MEASURES: Visual Analogue scale (VAS),
      The Timed Get up and Go test, Five Times Sit-to-Stand test, single leg standing,
      Yesavage test and Parkinson's Disease Questionnaire (PDQ-39). A descriptive
      analysis was performed on all study variables. RESULTS: The results showed a
      significant effect on time - of a high effect which indicates that the VAS scores
      (F 1.3; p < 0.001), Five time (F = 1.8; p = 0.001) and Get up and Go (F = 1.7; p
      < 0.001) significantly decreased in time, independent of the treatment group. In
      contrast, no significant differences were found in the results shown on the PDQ
      39 scale, finding only changes in the section of social support (p < 0.001 F =
      18.63). CONCLUSIONS: The results of this 11-week controlled pilot trial suggest
      that aquatic Ai Chi applied twice weekly may potentially reduce Parkinsonian
      symptoms as measured on different motor symptoms, bradykinesia and rigidity.

PMID- 29458924
TI  - Effect of olfactory stimulation with essential oils on cardiovascular reactivity
      during the moving beans task in stroke patients with anxiety.
AB  - OBJECTIVE: To investigate the effect of olfactory stimulation with essential oils
      on cardiovascular reactivity during the "moving beans" rehabilitation task in
      stroke patients with anxiety. METHODS: Twenty-eight stroke patients participated
      in this study. Blood pressure and heart rate were measured before and after
      finger movement tasks (e.g., moving beans and the Purdue pegboard test).
      Olfactory stimulation with lavender oil, grapefruit oil, and distilled water were
      conducted during finger tasks. Anxiety was assessed using the State Trait Anxiety
      Inventory (STAI)-Y2 before the finger movement tasks. RESULTS: There were no
      significant changes in blood pressure or heart rate activity in both finger
      movement tasks when stimulation of lavender oil, grapefruit oil, and distilled
      water was applied. However, the change values of Delta diastolic blood pressure
      (DBP) associated with the moving beans task indicated a significant interaction
      between olfactory stimulations and the groups of STAI-Y2 scores (high vs low)
      (p=0.03), without main effects in the olfactory stimulations and the groups of
      STAI-Y2 scores. CONCLUSION: Olfactory stimulation with lavender and grapefruit
      oil may repress the exaggerated DBP response during the moving beans task in
      stroke patients with higher levels of trait anxiety symptoms.

PMID- 29458925
TI  - Is cupping blister harmful?-A proteomical analysis of blister fluid induced by
      cupping therapy and scald.
AB  - OBJECTIVE: Cupping therapy has a long history in traditional medicine especially
      in Asian countries. It was controversial whether cupping induced blisters are
      beneficial to healing effects, and the formation and content in the blisters
      remain unexplored. We aimed to identify and compare the molecular components of
      the blister fluid from the cupping therapy and the scalds to explore the
      necessary of inducing cupping induced blisters. METHODS: Fluid sample of blisters
      from fifteen patients receiving cupping therapy (Cupping group) and scald burns
      (Scald group) were collected in this study. Proteins from the blisters were
      separated by two-dimensional electrophoresis (2D-gel) and further analyzed by
      mass spectrometry. In addition, the changes in particular proteins were confirmed
      by Western blotting. RESULTS: The protein components are significantly different
      between blister from cupping therapy and scalds. The immune responses, oxidative
      stress and metabolic related proteins (Ig lambda-2 chain C regions, Ig gamma-1
      chain C region, hemopexin, prdx2, calmodulin, succinyl-CoA ligase and
      tetranectin) were increased, whereas the hemoglobin subunit beta was decreased in
      the Cupping group compared with the Scald group. CONCLUSIONS: Cupping induced
      blisters contain several proteins which relate to the activation of certain
      immune pathways including anti-oxidation, anti-apoptosis, tissue repairing and
      metabolic regulation. This proteomic analysis may indicate a significant clue to
      the mechanism study of cupping.

PMID- 29458926
TI  - Pregnancy outcomes in psychiatric patients treated with passiflora incarnata.
AB  - Passiflora incarnata is marketed in many countries as anxiolytic herbal
      supplement. Herbal medicines are natural products, but it doesn't mean they are
      always safe, especially during pregnancy. Passiflora incarnata extract was not
      teratogenic in experimental studies. However, there are no data available on
      possible effects on human pregnancy. Here we report five pregnant women with
      depression and/or anxiety who used passiflora incarnata in pregnancy. We observed
      one pregnancy resulting in neonatal death, two pregnancies with premature rupture
      of membranes, two infants with meconium aspiration syndrome and one infant with
      persistent pulmonary hypertension. No birth defects and no growth or
      developmental abnormalities for the live born infants were reported at 6 months
      of age. This observation is important since there have been no human reports
      about the use of passiflora incarnata in pregnant women. Pregnant women exposed
      to passiflora incarnata should be monitored, unless further data are available.

PMID- 29458927
TI  - The effect of pleasant olfactory mental imagery on the incidence and extent of
      atelectasis in patients after open heart surgery.
AB  - BACKGROUND AND PURPOSE: Atelectasis is the most common pulmonary complication
      after open heart surgery. This study was intended to examine the effects of
      pleasant olfactory mental imagery on postoperative atelectasis in patients
      undergoing open heart surgery. MATERIALS AND METHODS: This is a randomized
      controlled clinical trial. The sample consisted of 80 patients who were randomly
      assigned to either practice olfactory mental imagery (test group) or receive
      routine care (control group). A card with the image of roses was given to
      patients and they were asked to look at the image, visualize the scent of roses
      in the mind, and then sniff as much as possible, hold their breath for 2s and
      eventually exhale slowly through the nose. This procedure was consecutively
      repeated five times. After a fifteen-minute break, patients proceeded to practice
      olfactory mental imagery with other fruit images (banana, apple, and lemon). The
      test group executed the olfactory mental imagery for two hours in the morning and
      two hours in the afternoon on postoperative days 1 and 2. The control group
      received the routine ICU care. A questionnaire collected information on
      sociodemographic characteristics and clinical parameters. Chest radiographs were
      used to diagnose atelectasis, which were evaluated by the hospital radiologist.
      RESULTS: No statistically significant differences were observed between the two
      groups regarding sociodemographic, medical and surgical information. The
      incidence of atelectasis in the test group (40%, n=16) was significantly lower
      than in the control group (67.5%, n=27) on postoperative day 2 (p=0.02).
      CONCLUSION: Our findings suggest that olfactory mental imagery can improve
      respiratory function and reduce the risk of atelectasis in patients with cardiac
      surgery.

PMID- 29458928
TI  - Adjunctive Vitamin D in the treatment of non-remitted depression: Lessons from a
      failed clinical trial.
AB  - BACKGROUND: Many patients with depression fail to achieve remission after several
      consecutive treatments. Vitamin D deficiency is prevalent and new research
      suggests that it may have an impact on mood, primarily through an effect on
      neurotransmitters. Numerous observational studies suggest a relationship between
      low levels of vitamin D and increased incidence and severity of mood disorders. A
      small number of pilot studies have been undertaken but lack rigorous methodology
      required to draw conclusions about a clinical role for this nutrient in treatment
      resistant depression. METHODS: This study was designed as a randomized, double
      blind, placebo controlled intervention study administering a weekly (bolus) dose
      of 28 000IU of Vitamin D3 or placebo to 125 patients with non-remitted depression
      adjunct to current antidepressant medication. Patients were followed weekly for
      eight weeks plus a one month follow up. Outcomes measured included depression
      severity, serum vitamin D levels and safety. Due to slow recruitment during the
      first season, amendments were made. These included extending the age range to 18
      75 and removing the requirement for failing to respond to one pharmacologic
      antidepressant agent. The protocol was amended to reduce the burden on
      participants by changing the in-office visits to bi-weekly. Three additional
      tertiary psychiatric clinics were also added as trial sites. RESULTS: Over three
      recruitment period years (fall/winter), a total of 148 participants completed
      screening, 24 (16.2%) of whom qualified to participate in the study. Use of too
      many or no psychiatric medications, comorbid exclusionary psychiatric conditions,
      current use of a vitamin D supplement, and lack of participant compensation were
      the predominant reasons for ineligibility or unwillingness to participate. 9
      participants were successfully enrolled in the study, 7 (77.8%) of whom completed
      the trial as per the protocol. After the third season, futility was declared
      based on inability to enroll participants. The sample size of enrolled
      participants (7/125, 5.6%) lacks power to conduct a full assessment of findings.
      DISCUSSION: High accessibility of vitamin D, as well as a growing lack of
      equipoise in patients and clinicians about the potential ubiquitous benefits of
      vitamin D for Canadians, not just for mood disorders, resulted in a large
      proportion of ineligible potential participants. Limited funding provided to
      studies on natural health products hampered recruitment. The labile and
      fluctuating nature of non-remitted depression as well as frequent co-morbid
      conditions creates additional challenges for conducting trials in this
      population. Future studies assessing vitamin D in depression should consider our
      experiences in design and conduct of research. Innovations in clinical trial
      design such as preference trials or accepting patients already using vitamin D
      but not achieving an optimal target value are potential solutions to some of
      these challenges.

PMID- 29458929
TI  - Physical activity is associated with higher cognitive function among adults at
      risk for Alzheimer's disease.
AB  - OBJECTIVE: We evaluated the specific association between physical activity and
      cognitive function among a national sample of the broader U.S. adult population
      with a family history of Alzheimer's disease. METHODS: Data from the 1999-2002
      National Health and Nutrition Examination Survey (NHANES) were used to identify
      219 older adults, ages 60-85, with a family history of Alzheimer's disease. The
      Digit Symbol Substitution Test (DSST) was used to assess cognitive function, with
      physical activity assessed via a validated questionnaire. RESULTS: In an
      unadjusted model, older adults, who had at least one blood relative with
      Alzheimer's disease, had greater cognitive function when meeting MVPA guidelines
      in comparison to their inactive counterparts (beta=9.6; 95% CI: 4.6-14.7;
      P=0.001). After adjustments, results were attenuated, but still statistically
      significant (8.5; 95% CI: 4.0-13.0; P=0.001). CONCLUSION: In this national sample
      of individuals at risk for Alzheimer's disease, meeting physical activity
      guidelines was associated with higher cognitive function.

PMID- 29458930
TI  - Veterans in substance abuse treatment program self-initiate box gardening as a
      stress reducing therapeutic modality.
AB  - OBJECTIVES: To assess the experiences of a veteran initiated horticultural
      therapy garden during their 28-day inpatient Substance Abuse Residential
      Rehabilitation Treatment Program (SARRTP). DESIGN: Retrospective study. SETTING:
      Veterans Affairs Medical Center (VAMC), Salem, Virginia, USA INTERVENTIONS: Group
      interviews with veterans from the last SARRTP classes and individual interviews
      with VAMC greenhouse staff in summer of 2016. OUTCOME MEASURES: Time spent in
      garden, frequency of garden visits, types of passive and active garden
      activities, words describing the veterans' emotional reactions to utilizing the
      garden. RESULTS: In 3 summer months of 2016, 50 percent of the 56 veterans
      interviewed visited and interacted with the gardens during their free time.
      Frequency of visits generally varied from 3 times weekly to 1-2 times a day.
      Amount of time in the garden varied from 10min to 2h. The veterans engaged in
      active and/or passive gardening activities during their garden visits. The
      veterans reported feeling "calm", "serene", and "refreshed" during garden
      visitation and after leaving the garden. CONCLUSIONS: Although data was secured
      only at the end of the 2016 growing season, interviews of the inpatient veterans
      revealed that they used their own initiative and resources to continue the
      horticulture therapy program for 2 successive growing years after the original
      pilot project ended in 2014. These non-interventionist, therapeutic garden
      projects suggest the role of autonomy and patient initiative in recovery programs
      for veterans attending VAMC treatment programs and they also suggest the value of
      horticulture therapy as a meaningful evidence- based therapeutic modality for
      veterans.

PMID- 29458931
TI  - Assessment of the psychopathological effects of a horticultural therapy program
      in patients with schizophrenia.
AB  - OBJECTIVES: This study assessed the psychopathological effects of participation
      in a 10-session horticultural therapy program in patients with schizophrenia.
      DESIGN: The study design was pre and post test design of experimental and control
      groups. SETTING: Twenty-eight Korean patients with schizophrenia, recruited from
      a mental health clinic and two mental health rehabilitation centers in Suwon,
      South Korea, were voluntarily assigned to either a control group (average age:
      33.4+/-9.4years) or a horticultural therapy group (average age: 42.1+/
      13.0years). INTERVENTIONS: The participants in the horticultural therapy group
      participated in a 10-session horticultural therapy program designed around
      various plant cultivating activities. The horticultural therapy program involved
      sessions once a week from April 2017 to June 2017. MAIN OUTCOME MEASURES: A
      psychiatrist evaluated the psychopathological symptoms of schizophrenic patients
      in both groups. To assess the clinical psychopathological effects, the Korean
      version of the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric
      Rating Scale (BPRS) were used. RESULTS: The horticultural therapy group
      significantly improved in terms of positive, negative, and general symptoms on
      the PANSS after the 10-session horticultural therapy program. Moreover, the
      horticultural therapy group significantly improved in terms of clinical symptoms
      of schizophrenia in BPRS after the 10-session horticultural therapy program.
      However, there was no change in the PANSS and BPRS scores in the control group.
      CONCLUSIONS: This study showed the potential of horticultural therapy in
      improving psychopathological symptoms in psychiatric patients. Future studies
      should investigate the effects of long-term horticultural therapy program on the
      chronic symptoms of patients with schizophrenia.

PMID- 29458932
TI  - Efficacy of Arsenicum album 30cH in preventing febrile episodes following DPT
      HepB-Polio vaccination - a randomized, double-blind, placebo-controlled clinical
      trial.
AB  - BACKGROUND: Among the post-immunization adverse events, especially of Diphtheria
      Pertusis-Tetanus (DPT), fever is a common systemic reaction. There is anecdotal
      support for the use of the homeopathic medicine Arsenicum album in preventing
      post-vaccination fever. The investigators intended to evaluate its efficacy in
      preventing febrile episodes following vaccination. METHODS: In the community
      medicine out-patient of Mahesh Bhattacharyya Homoeopathic Medical College and
      Hospital, West Bengal, India, between August 2014 and January 2017, a double
      blind, randomized, placebo-controlled trial was conducted on 120 children (verum:
      60, placebo: 60) who presented for the 2nd and 3rd dose of DPT-HepB-Polio
      vaccination and reported febrile episodes following the 1st dose. Intervention
      used was Arsenicum album 30cH 6 doses or placebo (indistinguishable from verum),
      thrice daily for two subsequent days. Parents were advised to report any event of
      febrile attacks within 48h of vaccination, either directly or over telephone.
      RESULTS: The groups were comparable at baseline. Children reporting fever after
      the 2nd dose was 29.8% and 30.4% respectively for the homeopathy group and
      control group respectively [Relative Risk (RR)=1.008] with no significant
      difference (P=0.951) between groups. Again after the 3rd dose, children reporting
      fever were 31.5% and 28.3% respectively for the homeopathy group and control
      group respectively (RR=0.956) with no significant difference (P=0.719) between
      groups. CONCLUSION: Empirically selected Arsenicum album 30cH could not produce
      differentiable effect from placebo in preventing febrile episodes following DPT
      HepB-Polio vaccination. [Trial registration: CTRI/2017/02/007939].

PMID- 29458933
TI  - Effect of whole body cryotherapy interventions on health-related quality of life
      in fibromyalgia patients: A randomized controlled trial.
AB  - INTRODUCTION: Although fibromyalgia syndrome (SFM) affects 2-4 percent of adults,
      research has not identified a preferred therapeutic option for patients worldwide
      yet. Based on recent findings, it can be expected that whole body cryotherapy can
      improve health-reported quality of life by alleviating the symptoms of
      musculoskeletal pain and fatigue. OBJECTIVE: Our aim was to determine whether
      whole body cryotherapy only can result in improved perceived health and quality
      of life in fibromyalgia patients. METHODS: 24 patients with fibromyalgia
      diagnosis were randomized into 2 groups (n=11 in the whole body cryotherapy
      group, n=13 in the control group). In the whole body cryotherapy group, 10
      sessions of whole body cryotherapy were performed (in addition to usual care) in
      a standard cryotherapy room over a duration of 8days. Subjects in the control
      group did not change anything in their everyday activities. Quality of life was
      assessed just before and one month after treatment. RESULTS: Compared with the
      control group, patients in the whole body cryotherapy group reported
      significantly improved for health-reported quality of life. These effects lasted
      for at least one month following intervention. CONCLUSION: Based on these
      findings, whole body cryotherapy can be recommended as an effective clinically
      adjuvant approach in the improvement of health-related quality of life in
      fibromyalgia patients.

PMID- 29458934
TI  - Effect of aromatherapy on coping with premenstrual syndrome: A randomized
      controlled trial.
AB  - BACKGROUND AND AIM: Premenstrual Syndrome (PMS) is a health problem which begins
      approximately one week before menstruation in women occurs as a set of physical
      and psychological symptoms. This study aimed to determine the effect of
      aromatherapy on coping with premenstrual syndrome in university students.
      METHODS: A randomized controlled trial design was used. This study included 40
      students in the intervention and 37 students in the control groups. Data was
      collected by questionnaire form and PMS scale. The intervention and control
      groups were followed up for 3 cycles in terms of PMS symptoms. The method of
      inhalation aromatherapy by lavender oil was applied for 5 sessions on average for
      each cycle. RESULTS: When PMS mean scores of the intervention and control groups
      during 3 follow-up periods were compared, it was found that there is a
      statistically significant difference between intervention and control groups
      (p<0.05). It was determined that there is a statistically significant difference
      between the groups in terms of PMS scale and sub-dimensions of anxiety,
      depressive affect, nervousness, pain, bloating, depressive thoughts mean scores
      of pre-test and 3rd follow-up (p<0.05), CONCLUSIONS: It was concluded that
      inhalation aromatherapy can be used for coping with PMS. It is recommended that
      the students suffering from PMS problems should be informed on the inhalation
      therapy by lavender oil.

PMID- 29458935
TI  - Everybody was Kung-Fu fighting-The beneficial effects of Tai Chi Qigong and self
      defense Kung-Fu training on psychological and endocrine health in middle aged and
      older men.
AB  - BACKGROUND: Higher age is associated to a variety of physical and mental
      disorders. Age-related changes in steroid secretion have been suggested to be an
      underlying mechanism leading to frailty, depression, and sexual dysfunction.
      However, Tai chi qigong and similar forms of exercise have been shown to improve
      a great variety of health-related parameters in older individuals. METHODS: We
      examined 56 self-reporting healthy men actively practicing Tai chi qigong and/or
      self-defense Kung-fu and 55 age-matched self-reporting healthy controls. Saliva
      samples were obtained in a standardized procedure for subsequent quantification
      of circulating testosterone and cortisol levels. In addition, depressive
      symptoms, life satisfaction, and sexual health were assessesd via self-report
      questionnaires. RESULTS: Age was negatively associated with testosterone, while
      no association emerged for cortisol. Tai chi qigong and/or self-defense Kung-fu
      training was neither associated with testosterone nor cortisol. More weekly Tai
      chi qigong and/or self-defense Kung-fu training (4 or more times per week) was
      instead associated with a lower CT-ratio, less depressive symptoms, and higher
      life satisfaction compared to individuals, who trained only one to three times
      per week. More years of Tai chi qigong and/or self-defense Kung-fu training were
      associated with less depressive symptoms and higher life satisfaction but not
      with the CT-ratio. No significant associations emerged for Tai chi qigong and/or
      self-defense Kung-fu training and sexual health. When compared to the age-matched
      controls, there is a significant effect of Tai chi, qigong and/or self-defense
      Kung-fu on the CT-ratio. Contrast analyses revealed a significantly lower CT
      ratio for the high training load group in contrast to the low training load
      group. Further, in contrast to the control group, the low training load group
      exhibits a significantly higher CT-ratio. For depression, contrast analyses
      revealed a significantly lower level of depression in the high training load
      group compared to the control group. CONCLUSION: The results indicate that Tai
      chi qigong and/or self-defense Kung-fu training is beneficially associated with
      steroid secretion patterns and mental health in aging men, when training is
      performed with a frequency of 4 or more trainings per week. However, the high
      frequency training and control group show similar steroid secretion patterns
      suggesting an inverted U-shaped association between Tai chi qigong and/or self
      defense Kung-fu training frequency and the CT-ratio in aging men. More research
      is needed to elucidate the underlying mechanism of this association. Still, Tai
      chi qigong and/or self-defense Kung-fu training provides a promising prevention
      strategy against age-related physical and mental deterioration in aging men.

PMID- 29458936
TI  - Effects of combined and resistance training on the inflammatory profile in breast
      cancer survivors: A systematic review.
AB  - OBJECTIVE: The present systematic review aimed to verify the effect of resistance
      and combined training on the inflammatory profile of breast cancer survivors.
      DESIGN: The searches were made on the platforms PsycINFO, PubMed, Cochrane,
      Science Direct and Scopus, from 1996 to 2017, using the keywords: cancer
      survivors, cancer treatment, cancer patients, breast cancer, inflammation,
      inflammatory profile, immune function, resistance training, strength training,
      weight training, physical activity, concurrent training and combined training.
      References of selected articles were also considered. Seven studies fulfilled the
      criteria adopted for analysis. RESULTS: None of these studies have shown reduced
      inflammatory markers in breast cancer survivors undergoing combined or isolated
      resistance training. CONCLUSIONS: It is not yet possible to conclude which
      resistance and/or combination training protocol is capable of improving the short
      term inflammatory profile in this population. Future studies should seek to
      establish how structural training variables (intensity, volume, density, intra-
      and inter-series recovery, among others) act on anti-inflammatory processes in
      breast cancer survivors.

PMID- 29458937
TI  - Chinese herbal medicine Dengzhan Shengmai capsule as adjunctive treatment for
      ischemic stroke: A systematic review and meta-analysis of randomized clinical
      trials.
AB  - OBJECTIVE: The existing eligible randomized controlled trials (RCTs) were
      critically appraised for the effectiveness and safety of Chinese herbal medicine
      Dengzhan Shenmai for ischemic stroke. DESIGN: Systematic review and meta-analysis
      (CRD42016042914, http://www.crd.york.ac.uk/PROSPERO). METHODS: Six electronic
      databases were searched from inception to May 2016. Risk ratio (RR) and mean
      difference (MD) with a 95% confidence interval (CI) were used as effect estimates
      using RevMan 5.3. Meta-analysis was performed where data were available. A
      summary of finding table was generated by the GRADEpro (version 3.6). RESULTS: We
      identified 14 RCTs involving 5206 participants. Majority of the included trials
      were of high risk of bias in methodological quality. For acute ischemic stroke,
      adding DZSM capsule to conventional therapy achieved higher Barthel Index scores
      (MD 22.37, 95% CI 21.34-23.40), lower neurological function deficit scores (MD -
      3.73, 95% CI -5.27 to -2.19) and lower recurrence rate (RR 0.22, 95% CI 0.10,
      0.46). For patients in their convalescence (or sequelae) stage of ischemic
      stroke, DZSM capsule was superior in improving quality of life (MD 28.8, 95% CI
      7.10-50.50) and recurrence rate (RR 0.71, 95% CI 0.51-0.99) compared to placebo.
      No trials reported serious adverse events. CONCLUSION: DZSM capsule appears to
      improve neurological function, quality of life, and reduce recurrence rate based
      on conventional therapy for ischemic stroke. DZSM capsule seems generally safe
      for clinical application. However, the findings of benefit are inconclusive due
      to generally weak evidence, and further large, rigorous trials are still
      warranted.

PMID- 29458938
TI  - Effects of tongue cleaning on Ayurvedic digestive power and oral health-related
      quality of life: A randomized cross-over study.
AB  - OBJECTIVES: The effect of tongue cleaning on digestive power is mentioned in
      Ayurvedic information sources. However, no study has yet evaluated this. We aimed
      to evaluate the effects of tongue cleaning on digestive power from Ayurvedic
      viewpoint, and on oral health-related quality of life (OHRQoL) in healthy adults.
      DESIGN: Randomized cross-over. INTERVENTIONS: We recruited healthy adults aged 20
      60 years. After randomization, the immediate intervention group started tongue
      cleaning with a tongue scraper every morning for 4 weeks, and then waited for 4
      weeks. The delayed intervention group initially waited for 4 weeks, and then
      started tongue cleaning in the same way. MAIN OUTCOME MEASURES: We assessed the
      outcomes using the questionnaire on digestive power from Ayurvedic viewpoint, and
      the General Oral Health Assessment Index for OHRQoL. We estimated the effects of
      tongue cleaning using generalized estimating equations (GEE). We also conducted a
      sensitivity analysis, by comparing the changes in outcomes during the first 4
      weeks of both groups. RESULTS: Of 58 participants, 57 completed the study. In GEE
      analysis, tongue cleaning showed improvement in some components of Ayurvedic
      digestive power represented by fecal and body conditions. For example, the odds
      ratio for improvement of constipation was 2.80 (95% CI: 1.04-7.58). The General
      Oral Health Assessment Index score was significantly increased by 4.33 points
      (95% CI: 2.18-6.48) after tongue cleaning. In sensitivity analyses, the trends of
      the results were similar to the main GEE analyses. CONCLUSIONS: Tongue cleaning
      may be an effective method to improve digestive power and OHRQoL.

PMID- 29458939
TI  - Association between mindfulness and interoceptive accuracy in patients with
      diabetes: Preliminary evidence from blood glucose estimates.
AB  - OBJECTIVE: Mindfulness-based interventions, which increase dispositional
      mindfulness, may be useful adjunctive therapies for patients with chronic
      diseases, including diabetes. One way that mindfulness may benefit patients with
      diabetes is by fostering more accurate interoception, particularly in the form of
      blood glucose estimate accuracy. Many people with diabetes regulate their
      behavior based on estimates of their blood glucose levels from interoception, but
      they vary in estimate accuracy. Therefore, our objective was to conduct a
      preliminary test of the hypothesis that, in a sample of patients with diabetes,
      more mindful individuals would demonstrate greater blood glucose estimate
      accuracy. METHODS: In a cross-sectional study, patients (N=28) with type 2
      diabetes estimated their blood glucose levels immediately before their actual
      levels were assessed. Participants also completed two measures of mindfulness:
      one assessing general dispositional mindfulness and another assessing mindfulness
      specifically in the face of difficulty. RESULTS: Although general dispositional
      mindfulness was unrelated to blood glucose estimate accuracy, individuals who
      reported more mindfulness during difficulties were approximately four times more
      likely to meet established accuracy criteria. CONCLUSIONS: Mindfulness
      specifically during difficulties might play a role in disease-relevant
      interoception for patients with diabetes. Future research should aim to replicate
      this finding in larger and different samples, and to examine the potential role
      of mindfulness during difficulties in mindfulness-based interventions for
      patients with diabetes.

PMID- 29458941
TI  - 2017: It was a Very Good Year.

PMID- 29458940
TI  - The effects of preoperative aromatherapy massage on anxiety and sleep quality of
      colorectal surgery patients: A randomized controlled study.
AB  - AIMS: To examine the effects of aromatherapy massage on anxiety and sleep quality
      in patients undergoing colorectal surgery in the preoperative period. BACKGROUND:
      In recent years, there has been an increase in the number of studies conducted on
      aromatherapy massage. It is stated that studies conducted on aromatherapy massage
      for anxiety and sleep quality reveal contradictory results and that more research
      is required on the issue. DESIGN: A randomized controlled trial. METHODS: Eighty
      patients undergoing colorectal surgery were randomly assigned to experimental and
      control group. To the experimental group (n = 40), aromatherapy massage was
      applied in accordance with the "Back Massage Guide" using 5% lavender oil
      (Lavandula Hybrida) for ten minutes before surgery and the morning of surgery.
      The control group received standard nursing care in compliance with the hospital
      procedure. Data were obtained by the State Anxiety Inventory (SAI) and Richard
      Campbell Sleep Questionnaire (RCSQ). Results were analyzed using the t-test, Chi
      square test or Fisher's exact test. RESULTS: There was no baseline difference
      between the groups. A statistically significant difference was found between the
      experimental and control group in terms of the SAI and RCSQ mean scores recorded
      on the morning of surgery. It was determined that the SAI and RCSQ mean score of
      the experimental group after aromatherapy massage on the morning of surgery
      decreased when compared to that of the evening before surgery. CONCLUSIONS: It
      was found that aromatherapy massage with lavender oil increased the sleep quality
      and reduced the level of anxiety in patients with colorectal surgery in the
      preoperative period.

PMID- 29458942
TI  - Realism on the rocks: Novel success and James Hutton's theory of the earth.
AB  - In this paper, I introduce a new historical case study into the scientific
      realism debate. During the late-eighteenth century, the Scottish natural
      philosopher James Hutton made two important successful novel predictions. The
      first concerned granitic veins intruding from granite masses into strata. The
      second concerned what geologists now term "angular unconformities": older
      sections of strata overlain by younger sections, the two resting at different
      angles, the former typically more inclined than the latter. These predictions, I
      argue, are potentially problematic for selective scientific realism in that
      constituents of Hutton's theory that would not be considered even approximately
      true today played various roles in generating them. The aim here is not to
      provide a full philosophical analysis but to introduce the case into the debate
      by detailing the history and showing why, at least prima facie, it presents a
      problem for selective realism. First, I explicate Hutton's theory. I then give an
      account of Hutton's predictions and their confirmations. Next, I explain why
      these predictions are relevant to the realism debate. Finally, I consider which
      constituents of Hutton's theory are, according to current beliefs, true (or
      approximately true), which are not (even approximately) true, and which were
      responsible for these successes.

PMID- 29458944
TI  - The naturalism of the sciences.
AB  - The sciences are characterized by what is sometimes called a "methodological
      naturalism," which disregards talk of divine agency. In response to those who
      argue that this reflects a dogmatic materialism, a number of philosophers have
      offered a pragmatic defense. The naturalism of the sciences, they argue, is
      provisional and defeasible: it is justified by the fact that unsuccessful
      theistic explanations have been superseded by successful natural ones. But this
      defense is inconsistent with the history of the sciences. The sciences have
      always exhibited what we call a domain naturalism. They have never invoked divine
      agency, but have always focused on the causal structure of the natural world. It
      is not the case, therefore, that the sciences once employed theistic explanations
      and then abandoned them. The naturalism of the sciences is as old as science
      itself.

PMID- 29458943
TI  - A role for spatiotemporal scales in modeling.
AB  - Bogen and Woodward's distinction between data and phenomena raises the need to
      understand the structure of the data-to-phenomena and theory-to-phenomena
      inferences. I suggest that one way to study the structure of these inferences is
      to analyze the role of the assumptions involved in the inferences: What kind of
      assumptions are they? How do these assumptions contribute to the practice of
      identifying phenomena? In this paper, using examples from atmospheric dynamics, I
      develop an account of the practice of identifying the target in the data-to
      phenomena and theory-to-phenomena inferences in which assumptions about
      spatiotemporal scales play a central role in the identification of parameters
      that describe the target system. I also argue that these assumptions are not only
      empirical but they are also idealizing and abstracting. I conclude the paper with
      a reflection on the role of idealizations in modeling.

PMID- 29458945
TI  - Chance, determinism and the classical theory of probability.
AB  - This paper situates the metaphysical antinomy between chance and determinism in
      the historical context of some of the earliest developments in the mathematical
      theory of probability. Since Hacking's seminal work on the subject, it has been a
      widely held view that the classical theorists of probability were guilty of an
      unwitting equivocation between a subjective, or epistemic, interpretation of
      probability, on the one hand, and an objective, or statistical, interpretation,
      on the other. While there is some truth to this account, I argue that the tension
      at the heart of the classical theory of probability is not best understood in
      terms of the duality between subjective and objective interpretations of
      probability. Rather, the apparent paradox of chance and determinism, when viewed
      through the lens of the classical theory of probability, manifests itself in a
      much deeper ambivalence on the part of the classical probabilists as to the
      rational commensurability of causal and probabilistic reasoning.

PMID- 29458946
TI  - Heuristic analogy in Ars Conjectandi: From Archimedes' De Circuli Dimensione to
      Bernoulli's theorem.
AB  - This article investigates the way in which Jacob Bernoulli proved the main
      mathematical theorem that undergirds his art of conjecturing-the theorem that
      founded, historically, the field of mathematical probability. It aims to
      contribute a perspective into the question of problem-solving methods in
      mathematics while also contributing to the comprehension of the historical
      development of mathematical probability. It argues that Bernoulli proved his
      theorem by a process of mathematical experimentation in which the central
      heuristic strategy was analogy. In this context, the analogy functioned as an
      experimental hypothesis. The article expounds, first, Bernoulli's reasoning for
      proving his theorem, describing it as a process of experimentation in which
      hypothesis-making is crucial. Next, it investigates the analogy between his
      reasoning and Archimedes' approximation of the value of pi, by clarifying both
      Archimedes' own experimental approach to the said approximation and its heuristic
      influence on Bernoulli's problem-solving strategy. The discussion includes some
      general considerations about analogy as a heuristic technique to make
      experimental hypotheses in mathematics.

PMID- 29458947
TI  - A coherentist conception of ad hoc hypotheses.
AB  - What does it mean for a hypothesis to be ad hoc? One prominent account has it
      that ad hoc hypotheses have no independent empirical support. Others have viewed
      ad hoc judgements as stemming from a lack of unifiedness of the amended theory.
      Still others view them as merely subjective. Here I critically review these views
      and defend my own Coherentist Conception of Ad hocness by working out its
      conceptual and descriptive attractions.

PMID- 29458948
TI  - Leibniz on the requisites of an exact arithmetical quadrature.
AB  - In this paper we will try to explain how Leibniz justified the idea of an exact
      arithmetical quadrature. We will do this by comparing Leibniz's exposition with
      that of John Wallis. In short, we will show that the idea of exactitude in
      matters of quadratures relies on two fundamental requisites that, according to
      Leibniz, the infinite series have, namely, that of regularity and that of
      completeness. In the first part of this paper, we will go deeper into three main
      features of Leibniz's method, that is: it is an infinitesimal method, it looks
      for an arithmetical quadrature and it proposes a result that is not approximate,
      but exact. After that, we will deal with the requisite of the regularity of the
      series, pointing out that, unlike the inductive method proposed by Wallis,
      Leibniz propounded some sort of intellectual recognition of what is invariant in
      the series. Finally, we will consider the requisite of completeness of the
      series. We will see that, although both Wallis and Leibniz introduced the
      supposition of completeness, the German thinker went beyond the English
      mathematician, since he recognized that it is not necessary to look for a number
      for the quadrature of the circle, given that we have a series that is equal to
      the area of that curvilinear figure.

PMID- 29458949
TI  - What does interdisciplinarity look like in practice: Mapping interdisciplinarity
      and its limits in the environmental sciences.
AB  - In this paper we take a close look at current interdisciplinary modeling
      practices in the environmental sciences, and suggest that closer attention needs
      to be paid to the nature of scientific practices when investigating and planning
      interdisciplinarity. While interdisciplinarity is often portrayed as a medium of
      novel and transformative methodological work, current modeling strategies in the
      environmental sciences are conservative, avoiding methodological conflict, while
      confining interdisciplinary interactions to a relatively small set of pre
      existing modeling frameworks and strategies (a process we call crystallization).
      We argue that such practices can be rationalized as responses in part to
      cognitive constraints which restrict interdisciplinary work. We identify four
      salient integrative modeling strategies in environmental sciences, and argue that
      this crystallization, while contradicting somewhat the novel goals many have for
      interdisciplinarity, makes sense when considered in the light of common
      disciplinary practices and cognitive constraints. These results provide cause to
      rethink in more concrete methodological terms what interdisciplinarity amounts
      to, and what kinds of interdisciplinarity are obtainable in the environmental
      sciences and elsewhere.

PMID- 29458950
TI  - A reply to Craver and Povich on the directionality of distinctively mathematical
      explanations.

PMID- 29458951
TI  - Radiologists: A Keystone of Multidisciplinary Oncology Practice.

PMID- 29458952
TI  - Post-Vacuum-Assisted Stereotactic Core Biopsy Clip Displacement: A Comparison
      Between Commercially Available Clips and Surgical Clip.
AB  - PURPOSE: The placement of localization clips following percutaneous biopsy is a
      standard practice for a variety of situations. Subsequent clip displacement
      creates challenges for imaging surveillance and surgical planning, and may cause
      confusion amongst radiologists and between surgeons and radiologists. Many causes
      have been attributed for this phenomenon including the commonly accepted
      "accordion effect." Herein, we investigate the performance of a low cost surgical
      clip system against 4 commercially available clips. METHODS: We retrospectively
      reviewed 2112 patients who underwent stereotactic vacuum-assisted core biopsy
      followed by clip placement between January 2013 and June 2016. The primary
      performance parameter compared was displacement >10 mm following vacuum-assisted
      stereotactic core biopsy. Within the group of clips that had displaced, the
      magnitude of displacement was compared. RESULTS: There was a significant
      difference in displacement among the clip types (P < .0001) with significant
      pairwise comparisons between pediatric surgical clips and SecureMark (38% vs 28%;
      P = .001) and SenoMark (38% vs 27%; P = .0001) in the proportion displaced. The
      surgical clips showed a significant magnitude of displacement of approximately
      25% greater average distance displaced. CONCLUSIONS: As a whole, the commercial
      clips performed better than the surgical clip after stereotactic vacuum-assisted
      core biopsy suggesting the surrounding outer component acts to anchor the central
      clip and minimizes clip displacement. The same should apply to tomosynthesis
      guided biopsy.

PMID- 29458953
TI  - Clinical Image Quality and Sensitivity in an Organized Mammography Screening
      Program.
AB  - PURPOSE: The study sought to examine the association between clinical image
      quality of mammograms and screening sensitivity. METHODS: Four radiologists
      evaluated the clinical image quality of 374 invasive screen-detected cancers and
      356 invasive interval breast cancers for which quality evaluation of screening
      mammograms could be assessed from cancers diagnosed among participants in the
      Quebec Breast Cancer Screening Program in 2007. Quality evaluation was based on
      the Canadian Association of Radiologists accreditation criteria, which are
      similar to those of the American College of Radiology. The association between
      clinical quality and screening sensitivity was assessed by logistic regression.
      Adjusted sensitivity and adjusted sensitivity ratios were obtained through
      marginal standardization. No institutional review board approval was required.
      RESULTS: A proportion of 28% (206 of 730) of screening mammograms had lower
      overall quality for the majority of assessments. Positioning was the quality
      attribute that was the most frequently deficient. The 2-year screening
      sensitivity reached 68%. Sensitivity of screening was not statistically
      associated with the overall quality (ratio of 2-year sensitivity = 1.03; 95%
      confidence interval: 0.93-1.15) or with any quality attributes (positioning,
      exposure, compression, sharpness, artifacts, contrast). Results were similar for
      the 1-year sensitivity. CONCLUSIONS: Although not all mammograms in the Quebec
      screening program met the optimum quality required by the Canadian Association of
      Radiologists or American College of Radiology accreditation, the screening
      mammograms produced in this population-based organized screening program reached
      a high enough level of quality so that the remaining variation in quality is too
      little to impair screening sensitivity.

PMID- 29458954
TI  - Irreversible Electroporation in Hepatopancreaticobiliary Tumours.
AB  - Hepatopancreaticobiliary tumours are often diagnosed at an advanced disease
      stage, in which encasement or invasion of local biliary or vascular structures
      has already occurred. Irreversible electroporation (IRE) is an image-guided
      tumour ablation technique that induces cell death by exposing the tumour to high
      voltage electrical pulses. The cellular membrane is disrupted, while sparing the
      extracellular matrix of critical tubular structures. The preservation of tissue
      integrity makes IRE an attractive treatment option for tumours in the vicinity of
      vital structures such as splanchnic blood vessels and major bile ducts. This
      article reviews current data and discusses future trends of IRE for
      hepatopancreaticobiliary tumours.

PMID- 29458955
TI  - Percutaneous Liver Tumour Ablation: Image Guidance, Endpoint Assessment, and
      Quality Control.
AB  - Liver tumour ablation nowadays represents a routine treatment option for patients
      with primary and secondary liver tumours. Radiofrequency ablation and microwave
      ablation are the most widely adopted methods, although novel techniques, such as
      irreversible electroporation, are quickly working their way up. The percutaneous
      approach is rapidly gaining popularity because of its minimally invasive
      character, low complication rate, good efficacy rate, and repeatability. However,
      matched to partial hepatectomy and open ablations, the issue of ablation site
      recurrences remains unresolved and necessitates further improvement. For
      percutaneous liver tumour ablation, several real-time imaging modalities are
      available to improve tumour visibility, detect surrounding critical structures,
      guide applicators, monitor treatment effect, and, if necessary, adapt or repeat
      energy delivery. Known predictors for success are tumour size, location, lesion
      conspicuity, tumour-free margin, and operator experience. The implementation of
      reliable endpoints to assess treatment efficacy allows for completion-procedures,
      either within the same session or within a couple of weeks after the procedure.
      Although the effect on overall survival may be trivial, (local) progression-free
      survival will indisputably improve with the implementation of reliable endpoints.
      This article reviews the available needle navigation techniques, evaluates
      potential treatment endpoints, and proposes an algorithm for quality control
      after the procedure.

PMID- 29458956
TI  - Incidence and Economic Impact of Incidental Findings on 18F-FDG PET/CT Imaging.
AB  - PURPOSE: The study sought to determine the incidence of incidental findings on
      whole-body positron emission tomography with computed tomography (PET/CT) imaging
      and the average costs of investigations to follow-up or further characterize
      incidental findings. METHODS: Imaging reports of 215 patients who underwent whole
      body PET/CT imaging were retrospectively reviewed. Our provincial picture
      archiving and communication system was queried and patient charts were reviewed
      to identify all investigations performed to follow-up incidental findings within
      1 year of the initial PET/CT study. Costs of follow-up imaging studies
      (professional and technical components) and other diagnostic tests and procedures
      were determined in Canadian dollars (CAD) and U.S. dollars (USD) using the 2015
      Ontario Health Insurance Plan Schedule of Benefits and Fees and 2016 U.S.
      Medicare Physician Fee Schedule, respectively. RESULTS: At least 1 incidental
      finding was reported in 161 reports (74.9%). The mean number of incidental
      findings ranged from 0.64 in patients <45 years of age to 2.2 in patients 75
      years of age and older. Seventy-five recommendations for additional
      investigations were made for 64 (30%) patients undergoing PET/CT imaging, and 14
      of those were carried out specifically to follow-up incidental findings. Averaged
      across all 215 patients, the total cost of investigations recommended to follow
      up incidental findings was CAD$105.51 (USD$127.56) per PET/CT study if all
      recommendations were acted on, and CAD$22.77 (USD$29.14) based on investigations
      actually performed. CONCLUSIONS: As the incidence of incidental findings
      increases with age and a larger proportion of elderly patients is expected as
      population demographics change, it will be increasingly important to consider
      incidental findings on PET/CT imaging with standardized approaches to follow-up.

PMID- 29458957
TI  - Magnetic Resonance Imaging and Computed Tomography of Cardiac Masses and
      Pseudomasses in the Atrioventricular Groove.
AB  - The atrioventricular (AV) groove constitutes the anatomic space separating the
      atria and ventricles. The AV groove is often difficult to visualize at
      echocardiography, and suspected lesions can be further assessed with cardiac
      computed tomography or magnetic resonance imaging. AV groove lesions may
      originate from within the AV groove or extend into this space from adjacent
      structures. The differential diagnosis for AV groove lesions is often wide, but a
      precise diagnosis can sometimes be made. This pictorial essay illustrates the
      magnetic resonance imaging and computed tomography appearance of common and
      uncommon AV groove lesions, and attempts to provide a logical framework for
      differential diagnosis when confronted with a known or suspected lesion at cross
      sectional imaging.

PMID- 29458958
TI  - The Accuracy of Colorectal Cancer Detection by Computed Tomography in the
      Unprepared Large Bowel in a Community-Based Hospital.
AB  - PURPOSE: This retrospective study examined the performance of general
      radiologists in a community-based hospital in detecting colorectal cancer (CRC)
      with computed tomography (CT) in the unprepared large bowel. METHODS: The
      pathology database at a community hospital over the past 7 years (2009-2015) was
      retrospectively analysed for pathologically proven CRC (924 cases). The
      provincial hospital information profile for these patients was reviewed to
      determine if they had an abdominal CT for any reason in the year prior to biopsy.
      Metrics such as age, sex, time between the CT and biopsy or surgery, whether CRC
      was initially detected by the radiologist, and if this was an emergency
      presentation was evaluated. In the cases where CRC was not identified, the CT
      scans were reanalysed to determine if the CRC was identifiable in retrospect. The
      sensitivity of detecting CRC by CT scan in the unprepared large bowel was
      calculated. RESULTS: Of the 924 biopsy proven CRC cases, 22% (207 of 924) of the
      patients had a CT prior to biopsy. Of these cases, 47% (97 of 207) presented on
      an emergency basis. Of the cases with imaging in the year prior, about 60% (125
      of 207) had cancer prospectively detected by the radiologist. Upon re-examination
      of the cases in which CRC was not initially detected, 59% were visualized in
      retrospect. CONCLUSIONS: Community general radiologists can successfully detect
      CRC with a high degree of accuracy. Reformatted images, bowel wall thickening
      when regional nodes are prominent, and minimizing oral contrast were helpful in
      improving detection.

PMID- 29458959
TI  - Is the Impella Device Really Useful to Unload the Left Ventricle During
      Extracorporeal Life Support?

PMID- 29458960
TI  - Challenging Standard-of-Care Paradigms in the Precision Oncology Era.
AB  - The pace of genomic and immunological breakthroughs in oncology is accelerating,
      making it likely that large randomized trials will increasingly become outdated
      before their completion. Traditional clinical research/practice paradigms must
      adapt to the reality unveiled by genomics, especially the need for customized
      drug combinations, rather than one-size-fits-all monotherapy. The raison-d'etre
      of precision oncology is to offer 'the right drug for the right patient at the
      right time', a process enabled by transformative tissue and blood-based genomic
      technologies. Genomically targeted therapies are most suitable in early disease,
      when molecular heterogeneity is less pronounced, while immunotherapy is most
      effective against tumors with unstable genomes. Next-generation cancer
      research/practice models will need to overcome the tyranny of tradition and
      emphasize an innovative, precise and personalized patient-centric approach.

PMID- 29458961
TI  - The Genetic/Non-genetic Duality of Drug 'Resistance' in Cancer.
AB  - Drug resistance is a serious impediment to the treatment of cancer. However, the
      mechanisms involved remain poorly understood. While it is widely held that the
      phenomenon is genetic in nature, emerging evidence suggests that non-genetic
      mechanisms may also be important. Furthermore, at least in some cases,
      refractoriness to treatment can be reversed by epigenetic reprogramming, and
      combination and intermittent therapies, as opposed to sustained monotherapy,
      appear more effective in attenuating it. Here we iterate the confusion in
      understanding the phenomenon by which cancer cells evade drug response and
      underscore the need to recognize the genetic/non-genetic duality of drug
      resistance in cancer. We discuss how ecological and evolutionary principles may
      help to reconcile the duality and may even offer new treatment strategies.

PMID- 29458963
TI  - B-Cell Metabolic Remodeling and Cancer.
AB  - Cells of the immune system display varying metabolic profiles to fulfill their
      functions. B lymphocytes overcome fluctuating energy challenges as they
      transition from the resting state and recirculation to activation, rapid
      proliferation, and massive antibody production. Only through a controlled
      interplay between metabolism, extracellular stimuli, and intracellular signaling
      can successful humoral responses be mounted. Alterations to this balance can
      promote malignant transformation of B cells. The metabolic control of B-cell fate
      is only partially understood. Here, we provide a compelling overview of the
      current state of the art and describe the main metabolic features of B cells
      during normal development and oncogenesis, with emphasis on the major B-cell
      transcriptional and metabolic regulators, including myelocytomatosis virus
      oncogene cellular homolog (Myc) and hypoxia-inducible factor 1-alpha (HIF
      1alpha).

PMID- 29458962
TI  - Re-Emergence of Dendritic Cell Vaccines for Cancer Treatment.
AB  - Dendritic cells (DCs) are essential in immunity owing to their role in activating
      T cells, thereby promoting antitumor responses. Tumor cells, however, hijack the
      immune system, causing T cell exhaustion and DC dysfunction. Tumor-induced T cell
      exhaustion may be reversed through immune checkpoint blockade (ICB); however,
      this treatment fails to show clinical benefit in many patients. While ICB serves
      to reverse T cell exhaustion, DCs are still necessary to prime, activate, and
      direct the T cells to target tumor cells. In this review we provide a brief
      overview of DC function, describe mechanisms by which DC functions are disrupted
      by the tumor microenvironment, and highlight recent developments in DC cancer
      vaccines.

PMID- 29458965
TI  - The Sympathetic Nervous System Drives Tumor Angiogenesis.
AB  - Neurobiology is increasingly contributing to cancer research. Recent work
      indicates that noradrenaline released by sympathetic adrenergic nerves in
      prostate cancer can stimulate beta-adrenoceptors in endothelial cells. This leads
      to the alteration of endothelial cell metabolism toward the inhibition of
      oxidative phosphorylation and the induction of an angiogenic switch that fuels
      cancer progression. These findings suggest that the sympathetic nervous system is
      a higher-level control of tumor angiogenesis that could be targeted in clinical
      oncology.

PMID- 29458966
TI  - Have Clinical Trials Properly Assessed c-Met Inhibitors?
AB  - The c-Met/HGF pathway is implicated in cancer progression and dissemination. Many
      inhibitors have been developed to target this pathway. Unfortunately, most trials
      have failed to demonstrate efficacy. However, clinical trials have not adequately
      tested the concept of c-Met pathway inhibition due to the lack of appropriate
      patient selection criteria.

PMID- 29458967
TI  - Improving Cancer Immunotherapies through Empirical Neoantigen Selection.
AB  - Targeting neoantigens has become an attractive strategy for cancer immunotherapy.
      Epitope prediction algorithms facilitate rapid selection of potential
      neoantigens, but are plagued with high false-positive and false-negative rates.
      Here we review ex vivo technologies for biological identification of neoantigens
      to improve empirical prioritization for immunotherapy.

PMID- 29458968
TI  - Influence of sad mood induction on implicit self-esteem and its relationship with
      symptoms of depression and anxiety.
AB  - BACKGROUND AND OBJECTIVES: Implicit self-esteem (ISE) refers to the valence of
      triggered associations when the self is activated. Despite theories, previous
      studies often fail to observe low ISE in depression and anxiety. It is feasible
      that sad mood is required to activate dysfunctional self-associations. The
      present study tested the following hypotheses: i) ISE is lower following a sad
      mood induction (SMI); ii) the relationship between ISE and level of
      depression/anxiety symptoms is relatively strong when ISE is measured during sad
      mood; iii) individuals with higher levels of depression/anxiety symptoms will
      show a relatively large decrease in ISE following a SMI. METHODS: In this mixed
      designed study, university students completed the self-esteem implicit
      association test (IAT) either at baseline (control condition; n = 46) or
      following a SMI (experimental condition; n = 49). To test the third hypothesis, a
      SMI and IAT were also given in the control condition. Both conditions completed
      self-report measures of explicit self-esteem (ESE), and symptoms of depression
      and anxiety. RESULTS: There was no support for the first two hypotheses, but some
      support that symptoms of anxiety correlated with larger decreases in ISE
      following a SMI which partly supported the third hypothesis. This disappeared
      when controlling for multiple testing. LIMITATIONS: Results are limited to non
      clinical participants. CONCLUSIONS: While ISE was robust against increases in sad
      mood, there was some tentative support that symptoms of anxiety were related to
      larger decreases in ISE following a SMI.

PMID- 29458964
TI  - Metabolism, Activity, and Targeting of D- and L-2-Hydroxyglutarates.
AB  - Isocitrate dehydrogenases (IDH1/2) are frequently mutated in multiple types of
      human cancer, resulting in neomorphic enzymes that convert alpha-ketoglutarate
      (alpha-KG) to 2-hydroxyglutarate (2-HG). The current view on the mechanism of IDH
      mutation holds that 2-HG acts as an antagonist of alpha-KG to competitively
      inhibit the activity of alpha-KG-dependent dioxygenases, including those involved
      in histone and DNA demethylation. Recent studies have implicated 2-HG in
      activities beyond epigenetic modification. Multiple enzymes have been discovered
      that lack mutations but that can nevertheless produce 2-HG promiscuously under
      hypoxic or acidic conditions. Therapies are being developed to treat IDH-mutant
      cancers by targeting either the mutant IDH enzymes directly or the pathways
      sensitized by 2-HG.

PMID- 29458969
TI  - Hospital readmission following open, single-stage, elective abdominal wall
      reconstructions using acellular dermal matrix affects long-term hernia recurrence
      rate.
AB  - BACKGROUND: We evaluated the incidence of and the risk factors for readmission in
      patients who underwent abdominal wall reconstruction (AWR) using acellular dermal
      matrix (ADM) and assess whether readmission affects AWR long-term outcomes.
      METHODS: A retrospective, single-center study of patients underwent AWR with ADM
      was conducted. The primary outcome was the incidence of unplanned readmission
      within 30 days after the initial discharge post-AWR. Secondary outcomes were
      surgical site occurrence (SSO) and hernia recurrence at follow-up. RESULTS: Of
      452 patients (mean age, 59 years; mean follow-up, 35 months), 29 (6.4%) were
      readmitted within 30 days. Most readmissions were due to SSO (44.8%) or wound
      infections (12.8%). The hernia recurrence rate was significantly higher in
      readmitted patients (17.2% vs 9.9%; P = 0.044). Wider defects, prolonged
      operative time, and coronary artery disease were independent predictors of
      readmission. CONCLUSIONS: Readmission is associated with hernia recurrence on
      long-term follow-up. SSO is the most common cause for readmission.

PMID- 29458970
TI  - Higher robotic colorectal surgery volume improves outcomes.
AB  - In this study we sought to assess the effect of surgeon volume on outcomes of
      robotic colorectal operations performed by surgeons with low or high volume
      across a large health system. We performed a retrospective review of colon or
      rectal resections performed between January 1, 2013 and January 1, 2017 within
      the Providence Health System Hospitals. Procedures were separated into those
      performed by surgeons with high volume (30 or more robotic cases per year) vs.
      low volume. A total of 8 high volume and 41 low volume robotic surgeons were
      included in the study. High volume surgeons had a significantly shorter length of
      hospital stay, lower conversion rate, and lower total hospital cost. There were
      no differences in complications or rate of readmission. Many studies have shown
      that outcomes improve with increased experience. These data suggest that if a
      surgeon maintains robotic experience there can be improvements in cost, length of
      stay and conversion rates.

PMID- 29458971
TI  - Continuous fractional-order Zero Phase Error Tracking Control.
AB  - A continuous time fractional-order feedforward control algorithm for tracking
      desired time varying input signals is proposed in this paper. The presented
      controller cancels the phase shift caused by the zeros and poles of controlled
      closed-loop fractional-order system, so it is called Fractional-Order Zero Phase
      Tracking Controller (FZPETC). The controlled systems are divided into two
      categories i.e. with and without non-cancellable (non-minimum-phase) zeros which
      stand in unstable region or on stability boundary. Each kinds of systems has a
      targeted FZPETC design control strategy. The improved tracking performance has
      been evaluated successfully by applying the proposed controller to three
      different kinds of fractional-order controlled systems. Besides, a modified quasi
      perfect tracking scheme is presented for those systems which may not have
      available future tracking trajectory information or have problem in high
      frequency disturbance rejection if the perfect tracking algorithm is applied. A
      simulation comparison and a hardware-in-the-loop thermal peltier platform are
      shown to validate the practicality of the proposed quasi-perfect control
      algorithm.

PMID- 29458972
TI  - Tracking control of air-breathing hypersonic vehicles with non-affine dynamics
      via improved neural back-stepping design.
AB  - This study considers the design of a new back-stepping control approach for air
      breathing hypersonic vehicle (AHV) non-affine models via neural approximation.
      The AHV's non-affine dynamics is decomposed into velocity subsystem and altitude
      subsystem to be controlled separately, and robust adaptive tracking control laws
      are developed using improved back-stepping designs. Neural networks are applied
      to estimate the unknown non-affine dynamics, which guarantees the addressed
      controllers with satisfactory robustness against uncertainties. In comparison
      with the existing control methodologies, the special contributions are that the
      non-affine issue is handled by constructing two low-pass filters based on model
      transformations, and virtual controllers are treated as intermediate variables
      such that they aren't needed for back-stepping designs any more. Lyapunov
      techniques are employed to show the uniformly ultimately boundedness of all
      closed-loop signals. Finally, simulation results are presented to verify the
      tracking performance and superiorities of the investigated control strategy.

PMID- 29458973
TI  - Robust and novel two degree of freedom fractional controller based on two-loop
      topology for inverted pendulum.
AB  - A rotary single inverted pendulum (RSIP) typically represents a space booster
      rocket, Segway and similar systems with unstable equilibrium. This paper proposes
      a novel two degree of freedom (2-DOF) fractional control strategy based on 2-loop
      topology for RSIP system which can be extended to control the systems with
      unstable equilibrium. It comprises feedback and feed-forward paths. Primary
      controller relates the perturbation attenuation while the secondary controller is
      accountable for set point tracking. To tune the parameters of proposed fractional
      controller a simple graphical tuning method based on frequency response is used.
      The study will serve the outstanding experimental results for both, stabilization
      and trajectory tracking tasks. The study will also serve to present a comparison
      of the performance of the proposed controller with the 1-DOF FOPID controller and
      sliding mode controller (SMC) for the RSIP system. Further to confirm the
      usability of the proposed controller and to avoid the random perturbations
      sensitivity, robustness, and stability analysis through fractional root-locus and
      Bode-plot is investigated.

PMID- 29458975
TI  - The interstitial macrophage: A long-neglected piece in the puzzle of lung
      immunity.
AB  - Lung macrophages have mostly been studied considering only their most accessible
      and well-defined representative, the alveolar macrophage (AM). In contrast, the
      identity and putative immune functions of their tissue counterpart, the
      interstitial macrophage (IM), have long remained much more elusive. Yet, recent
      evidence supports the notion that IMs perform important immune functions in the
      lung, notably in terms of innate immunoregulation. Here, we review current
      knowledge on the phenotype, ontogeny and function of IMs and propose strategies
      for the unambiguous identification and study of this important and dynamic lung
      innate immune cell population.

PMID- 29458974
TI  - Dynamic patterns and predictors of hydroxychloroquine nonadherence among Medicaid
      beneficiaries with systemic lupus erythematosus.
AB  - BACKGROUND: Hydroxychloroquine (HCQ) is the standard of care medication for most
      SLE patients, however nonadherence is common. We investigated longitudinal
      patterns and predictors of nonadherence to HCQ in a U.S. SLE cohort of HCQ
      initiators. METHODS: We used Medicaid data from 28 states to identify adults 18
      65 years with prevalent SLE. We included HCQ initiators following >=6 months
      without use, and required >=1 year of follow-up after first dispensing (index
      date). We used the proportion of days covered (PDC) to describe overall HCQ
      adherence (<80% = nonadherent) and novel group-based trajectory models (GBTM) to
      examine monthly patterns (<80% of days/month covered = nonadherent), during the
      first year of use. Multivariable multinomial logistic regression models were used
      to examine predictors of nonadherence. RESULTS: We identified 10,406 HCQ
      initiators with SLE. Mean age was 38 (+/-12) years, 94% were female, 42% black,
      31% white; 85% had a mean PDC < 80%. In our 4-group GBTM, 17% were persistent
      adherers, 36% persistent nonadherers, and 47% formed two dynamic patterns of
      partial adherence. Adherence declined for most patients over the first year.
      Compared to persistent adherers, the odds of nonadherence were increased for
      blacks and Hispanics vs. whites and for younger ages vs. older; increased SLE
      related comorbidities were associated with reduced odds of nonadherence for
      persistent nonadherers (0.95, 95% CI: 0.91-0.99). CONCLUSIONS: Among HCQ
      initiators with SLE, we observed poor adherence which declined for most over the
      first year of use. HCQ adherence is a dynamic behavior and further studies of
      associated predictors, outcomes, and interventions should reflect this.

PMID- 29458976
TI  - Small cell cancers of the female genital tract: Molecular and clinical aspects.
AB  - OBJECTIVE: Extra-pulmonary small cell carcinomas of the gynecologic tract (EPSCC
      GTs) are a rare group of aggressive malignancies associated with poor prognoses
      and limited treatment options. Here, we review the clinical and molecular aspects
      of EPSCC-GTs and discuss how understanding their molecular features can assist in
      their diagnosis and the identification of novel effective treatments. METHODS: We
      searched PubMed and Scopus for articles using the following keywords: "small cell
      carcinoma" in combination with "neuroendocrine", "ovary", "vagina", "fallopian
      tube", "vulva", "endometrium", "uterus", "cervix", or "gynecologic". Articles
      were limited to those published in English from January 1984 to October 2017.
      RESULTS: EPSCC-GTs account for 2% of all gynecologic malignancies. The molecular
      features of EPSCC-GTs are largely understudied and unknown, with the exception of
      small cell carcinoma (SCC) of the ovary, hypercalcemic type (SCCOHT) and SCC of
      the cervix (SCCC). In nearly all cases, SCCOHT displays mutation in a single
      gene, SMARCA4, a member of the SWI/SNF chromatin remodeling complex. The loss of
      expression of the SWI/SNF protein SMARCA2 is another feature of SCCOHT. Dual
      negative staining for SMARCA2 and SMARCA4 is specific for SCCOHT and is generally
      used by gynecologic pathologists for the accurate diagnosis of this malignancy.
      Mutational analysis of SCCC has shown alterations in PIK3CA, KRAS and TP53, of
      which the last is the most common, although other actionable mutations have been
      identified. The molecular features of other EPSCC-GTs are largely unknown.
      CONCLUSIONS: Due to their rarity, the majority of EPSCC-GTs are understudied and
      poorly understood. As demonstrated in the case of SCCOHT, unraveling the
      mutational profiles of these tumors can lead to improved diagnosis and the
      identification of novel therapeutic targets.

PMID- 29458977
TI  - Hyperglycemia promotes insulin-independent ovarian tumor growth.
AB  - INTRODUCTION: Epithelial ovarian cancer (EOC) is notoriously difficult to
      diagnose in its earlier and more treatable stages, making it one of the deadliest
      cancers in women. Comorbid diabetes is associated with poor prognosis in EOC and
      pro-growth insulin signalling is often considered to be the driving factor.
      However, EOC cells are also highly glycolytic and insulin-independent glucose
      uptake is essential to their metabolism. Evidence of gluconeogenesis in cancer in
      vivo suggests that the normal concentration of circulating glucose does not meet
      the energy demands of the tumor and may therefore be a limiting factor in cancer
      cell metabolism. Diabetics have elevated blood glucose that has the potential to
      meet these energy demands and facilitate cancer progression. METHODS: To
      determine whether hyperglycemia is a potentially modifiable factor independent of
      insulin, orthotopic ovarian tumors were induced in mice with acute Type 1 (hypo
      insulinemic) or Type 2 (hyper-insulinemic) diabetes. RESULTS: Hyperglycemia
      accelerated the growth of ovarian tumors in a glucose concentration-dependent
      manner and significantly shortened overall survival. Reciprocally, the presence
      of a tumor improved impaired glucose tolerance in both Type 1 and Type 2
      diabetes. In mice with chronic Type 1 diabetes, hyperglycemia limited tumor
      growth without changing overall survival, indicating that systemic metabolic
      stress can accelerate time to death independent of primary tumor size. When
      modeled in vitro, long-term culture in 25mM vs 6mM glucose resulted in
      significantly different growth and metabolism. CONCLUSIONS: Taken together, this
      study shows that systemic metabolic disturbances can have a profound impact on
      both the growth of ovarian tumors and on overall survival.

PMID- 29458978
TI  - The paleoecology of Pleistocene birds from Middle Bed II, at Olduvai Gorge,
      Tanzania, and the environmental context of the Oldowan-Acheulean transition.
AB  - Fossil bird data (community composition and taphonomic profiles) are used here to
      infer the environmental context of the Oldowan-Acheulean transitional period at
      Olduvai Gorge, Tanzania. This is the first comprehensive report on the Middle Bed
      II avifauna and includes fossils excavated by the Olduvai Geochronology and
      Archaeology Project (OGAP) and recently rediscovered fossils collected by Mary
      Leakey. Crane, ibis, darter, owl, raptor, crow, and vulture are reported from Bed
      II for the first time. The presence of these taxa, absent earlier in this Bed,
      point to a general opening and drying of the landscape with grassland and open
      woodland expansion. Taxa associated with dense, emergent wetland vegetation, such
      as dabbling ducks and rails, are uncommon and less diverse than earlier in Bed
      II. This suggests more mature wetlands with clearer waters. Cormorants continue
      to be common, but are less diverse. Cormorants and other roosting taxa provide
      evidence of trees in the area. Compared to lowermost Bed II, the Middle to Upper
      Bed II landscape is interpreted here as more open and drier (but not necessarily
      more arid), with matured wetlands, scattered trees, and a greater expansion of
      grasslands.

PMID- 29458979
TI  - The effects of long duration chronic exposure to hexavalent chromium on single
      live cells interrogated by scanning electrochemical microscopy.
AB  - Chromium is a useful heavy metal which has been employed in numerous industry and
      house applications. However, there are several known health risks associated with
      its uses. Cr (VI) is a toxic heavy metal format which serves no essential
      biological role in humans. It has been associated with oxidative stress,
      cytotoxicity, and carcinogenicity. Contamination of groundwater or soil due to
      improper handling lead to long term environmental damage. This study explores the
      effects of long duration chronic exposure to Cr (VI) on live human cells. Herein,
      scanning electrochemical microscopy (SECM) depth scan imaging was employed to
      monitor the membrane permeability of single live human bladder cancer (T24) cells
      following incubation with various Cr (VI) concentration stimuli. SECM was used to
      provide insights into the long duration effects on membrane homeostasis of
      individual cells exposed to constant levels of Cr (VI). Further investigation of
      total population viability was performed by MTT assay. Dependent on the exposure
      time, transition between three distinct trends was observed. At short incubation
      times (<=1-3 h) with low concentrations of Cr (VI) (0-10 MUM), membrane
      permeability was largely unaffected. As time increased a decrease in membrane
      permeability coefficient was observed, reaching a minimum at 3-6 h. Following
      this a dramatic increase in membrane permeability was observed as cell viability
      decreased. Higher concentrations were also found to accelerate the timeframe at
      which these trends occurred. These findings further demonstrate the strength of
      SECM as a bioanalytical technique for monitoring cellular homeostasis.

PMID- 29458980
TI  - Right Lower Quadrant Abdominal Pain: Do Not Forget About Ovarian Torsion on the
      Computed Tomography Scan.
AB  - BACKGROUND: Abdominal pain is one of the most common chief complaints of patients
      presenting to emergency departments, and emergency physicians (EPs) often
      evaluate patients with right lower quadrant abdominal pain. Ovarian torsion is a
      rare cause of abdominal pain, but early diagnosis is essential for salvage of the
      affected ovary. The diagnostic study of choice for ovarian torsion is a pelvic
      ultrasound with color Doppler, but it is important for EPs and radiologists to be
      aware of findings of ovarian torsion that might appear on computed tomography
      (CT). CASE REPORT: We present a case of a young female with right lower quadrant
      abdominal pain with CT evidence of ovarian torsion that was not recognized; the
      patient was discharged and then called back when the study was over-read as
      concerning for ovarian torsion. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
      THIS?: The presence of radiographic findings associated with ovarian torsion on a
      CT scan should encourage an EP to order a pelvic ultrasound with color Doppler
      (if available) and obtain an obstetrics/gynecology consult.

PMID- 29458981
TI  - Re: A Novel Tool for Predicting Extracapsular Extension During Graded Partial
      Nerve Sparing in Radical Prostatectomy.

PMID- 29458982
TI  - Reply to Federico Gheza, Simone Crivellaro, and Gian Luca Baiocchi's Letter to
      the Editor re: Lee C. Zhao, Aaron C. Weinberg, Ziho Lee, et al. Robotic Ureteral
      Reconstruction Using Buccal Mucosa Grafts: A Multi-institutional Experience. Eur
      Urol 2018;73:419-26. Robotic Ureteral Reconstruction with Buccal Mucosal Graft: A
      Call Not To Lose Momentum.

PMID- 29458983
TI  - First Report of Prostate-specific Membrane Antigen-targeted Immunotherapy in
      Prostate Cancer: The Future is Bright.

PMID- 29458984
TI  - Risk Stratification in Active Surveillance: A Dynamic, Ever-Evolving Practice.

PMID- 29458985
TI  - Defining the Prognostic and Predictive Impact of Germline DNA Repair Mutations in
      Patients with Metastatic Castration-resistant Prostate Cancer.

PMID- 29458986
TI  - Re: Ettore Di Trapani, Alessandro Nini, Irene Locatelli, et al. Development of
      the First Model of Radical Prostatectomy in the Mouse: A Feasibility Study. Eur
      Urol 2018;73:482-4.

PMID- 29458987
TI  - Better Stories.

PMID- 29458988
TI  - Sublingual immunotherapy in children.

PMID- 29458989
TI  - Invasive Pulmonary Aspergillosis Due to Aspergillus Ustus in an Immunocompromised
      Patient.

PMID- 29458990
TI  - The AJO A Century Ago: Historical Review of Volume 1, 1918.

PMID- 29458991
TI  - Prevalence of the risk factors for QT prolongation and associated drug-drug
      interactions in a cohort of medical inpatients.
AB  - BACKGROUND/PURPOSE: Medical inpatients are at increased risk of QT interval
      prolongation due to multiple risk actors and QT prolonging drugs. This study
      aimed to identify the prevalence of risk factors for QT prolongation; QT
      prolonging medications; associated drug-drug interactions (QT-DDIs); their
      predictors; and TdP (torsades de pointes) risks of drugs. METHODS: This cohort
      study was carried out in medical wards of two tertiary hospitals in Khyber
      Pakhtunkhwa, Pakistan. The QT-DDIs were identified using Micromedex DrugReax(r)
      and AZCERT (Arizona Center for Education and Research on Therapeutics) QT drugs
      lists. AZCERT QT drugs lists were used to identify TdP risks. Logistic regression
      analysis was performed to identify predictors of QT-DDIs. RESULTS: Total 400
      patients were included in this study. The most frequent QT prolonging risk
      factors included use of >=1 QT prolonging drugs (74.5%), female gender (55%) and
      diabetes mellitus (36.3%). Total 487 QT prolonging drugs were identified.
      According to AZCERT classification, 33.8% of the interacting drugs were included
      in list-1 (known risk of TdP), 0.9% in list-2 (possible risk of TdP) and 58.8% in
      list-3 (conditional risk of TdP). The occurrence of QT-DDIs was significantly
      associated with >=10 prescribed medications (p = 0.01), chronic liver disease (p
      = 0.05), chronic obstructive pulmonary disease (p = 0.03), gastroenteritis (p =
      0.02), antimicrobials (p < 0.001), antiemetics (p < 0.001) and antinausea (p <
      0.001). CONCLUSION: A substantial number of patients were exposed to risk factors
      for QT prolongation; and QT prolonging drugs such as proton pump inhibitors,
      antimicrobials and diuretics which may lead to serious outcomes.

PMID- 29458992
TI  - Acute respiratory distress syndrome in a man with Epstein-Barr virus infection
      induced hypocomplementemic urticarial vasculitis.

PMID- 29458993
TI  - Longitudinal association of metabolic syndrome and dietary patterns: A 13-year
      prospective population-based cohort study.
AB  - BACKGROUND AND AIMS: Diet is a potential factor contributing to the development
      of the Metabolic Syndrome (MetS). This longitudinal study with repeated
      measurements of dietary intake was thus conducted to examine the longitudinal
      association between major dietary patterns and risk of MetS. METHODS AND RESULTS:
      The study was conducted within the framework of the Isfahan Cohort Study (ICS),
      in which 1387 participants were followed from 2001 to 2013. Validated food
      frequency questionnaire, anthropometric measurements, blood pressure, fasting
      serum lipids and blood sugars were evaluated in three phases of the study. Mixed
      effect Logistic and Cumulative Logit regressions were applied to evaluate the
      longitudinal associations between dietary patterns change and MetS and number of
      MetS components. Three dietary patterns were identified: Healthy, Iranian and
      Western dietary patterns. After adjustment for potential confounders, the higher
      scores of Healthy diet were inversely associated with the risk of MetS and number
      of MetS components (OR: 0.50, 95% CI: 0.36-0.70, OR: 0.52, 95% CI: 0.39-0.70,
      respectively). The greater adherence to the Iranian diet was positively
      associated with the risk of MetS and number of MetS components (OR: 1.28, 95% CI:
      1.01-1.65, OR: 1.45, 95% CI: 1.16-1.81, respectively). The Western dietary
      pattern did not show any significant associations. CONCLUSION: Adherence to a
      Healthy diet was associated with lower risk of MetS even in a developing country
      setting. However, the Iranian diet was positively associated with the risk of
      MetS. These results may guide the development of improved preventive nutrition
      interventions in this adult population.

PMID- 29458995
TI  - Acute transient myocardial ischemia: A common pathophysiological mechanism in
      takotsubo syndrome. Is it still a cardiomyopathy?

PMID- 29458996
TI  - Quantitative comparisons of three automated methods for estimating intracranial
      volume: A study of 270 longitudinal magnetic resonance images.
AB  - Total intracranial volume (TIV) is often used as a measure of brain size to
      correct for individual variability in magnetic resonance imaging (MRI) based
      morphometric studies. An adjustment of TIV can greatly increase the statistical
      power of brain morphometry methods. As such, an accurate and precise TIV
      estimation is of great importance in MRI studies. In this paper, we compared
      three automated TIV estimation methods (multi-atlas likelihood fusion (MALF),
      Statistical Parametric Mapping 8 (SPM8) and FreeSurfer (FS)) using longitudinal
      T1-weighted MR images in a cohort of 70 older participants at elevated
      sociodemographic risk for Alzheimer's disease. Statistical group comparisons in
      terms of four different metrics were performed. Furthermore, sex, education
      level, and intervention status were investigated separately for their impacts on
      the TIV estimation performance of each method. According to our experimental
      results, MALF was the least susceptible to atrophy, while SPM8 and FS suffered a
      loss in precision. In group-wise analysis, MALF was the least sensitive method to
      group variation, whereas SPM8 was particularly sensitive to sex and FS was
      unstable with respect to education level. In terms of effectiveness, both MALF
      and SPM8 delivered a user-friendly performance, while FS was relatively
      computationally intensive.

PMID- 29458997
TI  - Psychiatric Symptom Dimensions Are Associated With Dissociable Shifts in
      Metacognition but Not Task Performance.
AB  - BACKGROUND: Distortions in metacognition-the ability to reflect on and control
      other cognitive processes-are thought to be characteristic of poor mental health.
      However, it remains unknown whether such shifts in self-evaluation are due to
      specific alterations in metacognition and/or a downstream consequence of changes
      in decision-making processes. METHODS: Using perceptual decision making as a
      model system, we employed a computational psychiatry approach to relate
      parameters governing both decision formation and metacognitive evaluation to self
      reported transdiagnostic symptom dimensions in a large general population sample
      (N = 995). RESULTS: Variability in psychopathology was unrelated to either speed
      or accuracy of decision formation. In contrast, leveraging a dimensional
      approach, we revealed independent relationships between psychopathology and
      metacognition: a symptom dimension related to anxiety and depression was
      associated with lower confidence and heightened metacognitive efficiency, whereas
      a dimension characterizing compulsive behavior and intrusive thoughts was
      associated with higher confidence and lower metacognitive efficiency.
      Furthermore, we obtained a robust double dissociation-whereas psychiatric
      symptoms predicted changes in metacognition but not decision performance, age
      predicted changes in decision performance but not metacognition. CONCLUSIONS: Our
      findings indicate a specific and pervasive link between metacognition and mental
      health. Our study bridges a gap between an emerging neuroscience of decision
      making and an understanding of metacognitive alterations in psychopathology.

PMID- 29458998
TI  - Role of Striatal Direct Pathway 2-Arachidonoylglycerol Signaling in Sociability
      and Repetitive Behavior.
AB  - BACKGROUND: Endocannabinoid signaling plays an important role in regulating
      synaptic transmission in the striatum, a brain region implicated as a central
      node of dysfunction in autism spectrum disorder. Deficits in signaling mediated
      by the endocannabinoid 2-arachidonoylglycerol (2-AG) have been reported in mouse
      models of autism spectrum disorder, but a causal role for striatal 2-AG
      deficiency in phenotypes relevant to autism spectrum disorder has not been
      explored. METHODS: Using conditional knockout mice, we examined the
      electrophysiological, biochemical, and behavioral effects of 2-AG deficiency by
      deleting its primary synthetic enzyme, diacylglycerol lipase alpha (DGLalpha),
      from dopamine D1 receptor-expressing or adenosine A2a receptor-expressing medium
      spiny neurons (MSNs) to determine the role of 2-AG signaling in striatal direct
      or indirect pathways, respectively. We then used viral-mediated deletion of
      DGLalpha to study the effects of 2-AG deficiency in the ventral and dorsal
      striatum. RESULTS: Targeted deletion of DGLalpha from direct-pathway MSNs caused
      deficits in social interaction, excessive grooming, and decreased exploration of
      a novel environment. In contrast, deletion from indirect-pathway MSNs had no
      effect on any measure of behavior examined. Loss of 2-AG in direct-pathway MSNs
      also led to increased glutamatergic drive, which is consistent with a loss of
      retrograde feedback inhibition. Subregional DGLalpha deletion from the dorsal
      striatum produced deficits in social interaction, whereas deletion from the
      ventral striatum resulted in repetitive grooming. CONCLUSIONS: These data suggest
      a role for 2-AG deficiency in social deficits and repetitive behavior, and they
      demonstrate a key role for 2-AG in regulating striatal direct-pathway MSNs.

PMID- 29458999
TI  - Case Report: First Reported Combined Heart-Liver Transplant in a Patient With a
      Congenital Solitary Kidney.
AB  - We report a case of successful combined heart liver transplant in a patient with
      a congenital solitary kidney. The patient had normal renal function before
      combined heart-liver transplantation and developed acute kidney injury requiring
      slow continuous dialysis and subsequent intermittent dialysis for almost 8 weeks
      post transplantation. Her renal function recovered and she remains off dialysis
      now 7 months post transplantation. She only currently has mild chronic renal
      insufficiency. We believe this is the first reported case of successful heart
      liver transplant in a patient with a congenital solitary kidney.

PMID- 29459000
TI  - In vitro activity of various antibiotics against clinical strains of Legionella
      species isolated in Japan.
AB  - The activities of various antibiotics against 58 clinical isolates of Legionella
      species were evaluated using two methods, extracellular activity (minimum
      inhibitory concentration [MIC]) and intracellular activity. Susceptibility
      testing was performed using BSYEalpha agar. The minimum extracellular
      concentration inhibiting intracellular multiplication (MIEC) was determined using
      a human monocyte-derived cell line, THP-1. The most potent drugs in terms of MICs
      against clinical isolates were levofloxacin, garenoxacin, and rifampicin with
      MIC90 values of 0.015 MUg/ml. The activities of ciprofloxacin, pazufloxacin,
      moxifloxacin, clarithromycin, and azithromycin were slightly higher than those of
      levofloxacin, garenoxacin, and rifampicin with an MIC90 of 0.03-0.06 MUg/ml.
      Minocycline showed the highest activity, with an MIC90 of 1 MUg/ml. No resistance
      against the antibiotics tested was detected. No difference was detected in the
      MIC distributions of the antibiotics tested between L. pneumophila serogroup 1
      and L. pneumophila non-serogroup 1. The MIECs of ciprofloxacin, pazufloxacin,
      levofloxacin, moxifloxacin, garenoxacin, clarithromycin, and azithromycin were
      almost the same as their MICs, with MIEC90 values of 0.015-0.06 MUg/ml, although
      the MIEC of minocycline was relatively lower and that of rifampicin was higher
      than their respective MICs. No difference was detected in the MIEC distributions
      of the antibiotics tested between L. pneumophila serogroup 1 and L. pneumophila
      non-serogroup 1. The ratios of MIEC:MIC for rifampicin (8) and pazufloxacin (2)
      were higher than those for levofloxacin (1), ciprofloxacin (1), moxifloxacin (1),
      garenoxacin (1), clarithromycin (1), and azithromycin (1). Our study showed that
      quinolones and macrolides had potent antimicrobial activity against both
      extracellular and intracellular Legionella species. The present data suggested
      the possible efficacy of these drugs in treatment of Legionella infections.

PMID- 29459001
TI  - Three point transfusion risk score in hepatectomy: an external validation using
      the American College of Surgeons - National Surgical Quality Improvement Program
      (ACS-NSQIP).
AB  - BACKGROUND: Risk of red blood cell transfusion (RBCT) in partial hepatectomy is
      17-27%; strategies to reduce transfusions can be targeted in patients at
      increased risk. A Three Point Transfusion Risk Score (TRS) was previously
      developed to predict patients' risk of transfusion during and following
      hepatectomy. Here, it was subject to external validation using the ACS-NSQIP
      database. METHODS: TRIPOD guidelines were followed. A validation cohort was
      created with the ACS-NSQIP dataset. Risk groups for RBCT were created using the
      TRS: anemia (hematocrit <=36%), major liver resection (>=4 segments) and primary
      liver malignancy. Concordance index was used to assess the discrimination. The
      Hosmer-Lemeshow test for goodness of fit and calibration curves were used to
      assess calibration. RESULTS: Of 2854 hepatectomies, 18.9% received RBCT. The TRS
      stratified patients from low (8.5% risk of RBCT) to very high risk (40.6%) of
      RBCT. The concordance was 0.68 (95% CI 0.66-0.70). Hosmer-Lemeshow test and
      calibration curves supported good predictive performance of the model.
      CONCLUSION: The TRS adequately discriminated risk of RBCT in an external sample
      of patients undergoing hepatectomy. It provides a simple method to identify
      patients at high transfusion risk. It can be used to tailor patient blood
      management initiatives and reduce the use of RBCT.

PMID- 29459002
TI  - Reappraisal of post-pancreatectomy hemorrhage (PPH) classifications: do we need
      to redefine grades A and B?
AB  - BACKGROUND: Post-pancreatectomy hemorrhage (PPH) remains a major complication.
      The aim of this study was to reappraise the International Study Group of
      Pancreatic Surgery (ISGPS) classification. METHODS: The clinical utility of the
      ISGPS classification was tested on consecutive pancreatic resections performed at
      the Pancreas Institute of the University of Verona Hospital. RESULTS: PPH
      occurred in 65 of the 2429 patients (6.8%) undergoing pancreatic resection.
      Outcome of patients without PPH and with grade A PPH were comparable in terms of
      mortality, length of stay, ICU stay and readmission. Patients with grade B late
      and mild and grade B early and severe PPH had similar hospital stay and mortality
      rates, but differed in relaparotomy rate (10.1 vs. 81.2%, p < 0.01). Replacing
      "time of PPH onset" criterion with post-operative pancreatic fistula (POPF),
      severe PPH alone, mild PPH/POPF and severe PPH/POPF differed significantly for
      hospital stay (14 vs. 23 vs. 35 days, p < 0.01) and mortality rate (0 vs. 4 vs.
      25%, p = 0.05). CONCLUSION: Grade A PPH shared the same outcome of patients
      without PPH. Grade B PPH included two categories of patients with different
      treatment modalities. The use of "concomitant POPF" instead of "time of onset"
      segregated three discrete categories that differed significantly in terms of
      clinical outcomes and management.

PMID- 29459003
TI  - [Knowledge about Biosimilars in Primary Care: a study by the Spanish Society of
      Primary Care Physicians (SEMERGEN)].
AB  - INTRODUCTION: The objective of this study was to evaluate the awareness and
      training needs on biosimilar drugs in Primary Care (PC) physicians. MATERIAL AND
      METHODS: Descriptive cross-sectional study based on an on-line questionnaire with
      a total of 34 multiple choice questions, published on the SEMERGEN website. The
      main Knowledge areas were: biosimilar definition; regulatory and legal framework;
      prescription, traceability, interchangeability and pharmacovigilance;
      availability of biosimilars in the PC setting, and the biosimilars contribution
      to sustainability. The software used for the analysis and data processing was the
      Barbwin 7.5. RESULTS: An analysis was performed on the responses from 701
      questionnaires completed. There was a slight majority (57%) of women
      participants. The majority of participant worked in urban centres (60.91%). The
      definition of biosimilar was not known by 58% of those that responded, and 73%
      were unaware that the management of biosimilars and generics was not comparable.
      Most (84%) of those that responded were not aware that the studies required for
      the approval of biosimilars is different from reference biological medicines.
      Around two-thirds (66%) those that responded did not know of any biosimilars
      available in PC setting, and the 94% were also unaware of the Spanish legal
      framework for the management of biosimilar medicines. CONCLUSIONS: The current
      knowledge about biosimilars among PC physicians is low. The critical areas in
      need of further training include specific information on biosimilars currently
      available in PC setting, as well as key aspects regarding prescription,
      interchangeability and pharmacovigilance requirements. Six out of ten doctors do
      not know of any biosimilar used in PC in Spain.

PMID- 29459004
TI  - Does gastric conditioning decrease the incidence of cervical oesophagogastric
      anastomotic leakage?
AB  - INTRODUCTION: Oesophageal reconstruction by gastroplasty with cervical
      anastomosis has a higher incidence of dehiscence. The aim of the study is to
      analyse the incidence of anastomotic leakage in patients undergoing gastroplasty
      with cervical anastomosis following angiographic ischaemic conditioning of the
      gastric conduit. METHODS: Prospective analysis of patients who underwent gastric
      conditioning two weeks prior to oesophageal reconstruction, from January 2001 to
      January 2014. The conditioning was performed by angiographic embolization of the
      left and right gastric artery, and splenic artery. The main variable analysed was
      the incidence of anastomotic leakage in patients undergoing gastroplasty with
      cervical anastomosis. Secondary variables analysed were the result of the
      conditioning, complications arising from that procedure and in the postoperative
      period, and mean length of postconditioning and postoperative hospital stay.
      RESULTS: Gastric conditioning was indicated in 97 patients, with neoplasia being
      the most frequent aetiology motivating the oesophageal reconstruction (76%). 96
      procedures were successfully carried out, arterial embolization was complete in
      80 (83%). The morbidity rate was 13%, with no mortality. Postoperative morbidity
      was 45%; the most frequent complications associated with the surgery were
      respiratory problems. Six (7%) patients experienced cervical fistula, and all
      received conservative treatment. The rate of postoperative mortality was 7%.
      CONCLUSIONS: In our serie the incidence of anastomotic leakage in patients
      undergoing gastroplasty with cervical anastomosis following angiographic
      ischaemic conditioning is 7%. Angiographic ischaemic conditioning is a procedure
      with acceptable morbidity.

PMID- 29459005
TI  - Three Extreme Cases of Short Bowel Syndrome: STEP and Neovalves. Decision
      Algorithm.

PMID- 29459006
TI  - Diagnosis and staging of solid pseudopapillary neoplasms of the pancreas: The
      role of 18F-FDG PET/CT scan.

PMID- 29459007
TI  - Variability of fasting plasma glucose and the risk of painful diabetic peripheral
      neuropathy in patients with type 2 diabetes.
AB  - AIM: The relationship between glycaemic variability and painful diabetic
      peripheral neuropathy (PDPN) in patients with type 2 diabetes (T2D) is unclear.
      The aim of this study was to investigate whether variations in fasting plasma
      glucose (FPG), as represented by the coefficient of variation (CV), were
      associated with the risk of PDPN in patients with T2D. METHODS: This case
      control, retrospective study was conducted at a tertiary care hospital in Taiwan.
      We enrolled adults with T2D from January 1 through October 31, 2013. PDPN was
      diagnosed using the Michigan Neuropathy Screening Instrument (MNSI) and Douleur
      Neuropathique 4 (DN4) questionnaire. Variability in FPG was defined as a CV of
      visit-to-visit FPG for every 3-month interval during follow-up period before
      enrolment. RESULTS: A total of 2,773 patients were enrolled. One hundred patients
      with PDPN were randomly selected and paired with 175 consecutive patients with
      non-painful diabetic peripheral neuropathy and 351 patients with T2D without
      diabetic peripheral neuropathy, matched for age, gender, and diabetic duration.
      After multivariate adjustment, the FPG-CV was significantly associated with a
      risk of PDPN with a corresponding odds ratio of 4.08 (95% confidence interval
      [CI] of 1.60-10.42) and 5.49 (95% CI of 2.14-14.06) for FPG-CV in the third and
      fourth versus first FPG-CV quartiles, respectively, after considering glycated
      haemoglobin (HbA1c). CONCLUSION: Long-term variability as evaluated by FPG-CV was
      associated to the risk of PDPN in adults with T2D. However, further studies are
      needed to know whether the FPG-CV is not simply a marker of the ambient
      hyperglycaemia.

PMID- 29459008
TI  - Association of the SOD2 (rs2758339 and rs5746136) polymorphisms with the risk of
      heroin dependency and the SOD2 expression levels.
AB  - BACKGROUND: Superoxide dismutase-2 (SOD2, OMIM: 147460) is involved in the
      detoxification of superoxide anions. The SOD2 mRNA level is down-regulated in
      cells exposed to morphine. Oxidative stress plays an important role in drug
      dependency. The rs2758339 (A/C) is located in the vicinity of SP1 and NF-kappaB
      transcription element sequences and the rs5746136 (A/G) creates a new
      glucocorticoid receptor binding site. Taken together, it is hypothesized that
      these polymorphisms might be associated with the risk of heroin dependency (HD)
      and the SOD2 expression level. METHODS: To investigate the association between
      the SOD2 polymorphisms and the risk of HD, 442 heroin dependent persons and 799
      healthy controls were included. This study also, consisted of 77 healthy students
      of Shiraz University (Iran) to investigate the association between the SOD2
      polymorphisms and the gene expression level. RESULTS: The AC (OR = 0.72, 95% CI =
      0.56-0.93, P = 0.013) and CC (OR = 0.64, 95% CI = 0.45-0.92, P = 0.015) genotypes
      of the rs2758339 were negatively associated with the risk of HD. The AA genotype
      of the rs5746136 increased the risk of HD (OR = 1.46, 95% CI = 1.03-2.07, P =
      0.031). The AA haplotype was associated with the risk of HD (OR = 1.31, 95% CI =
      1.09-1.58, P = 0.004). There was no relationship between the study genotypes (or
      diplotypes) and the SOD2 expression level. CONCLUSION: The rs2758339 and
      rs5746136 polymorphisms of the SOD2 are associated with the risk of HD but not
      associated with the SOD2 expression level.

PMID- 29459009
TI  - Characterization of metabolic network of oxalic acid biosynthesis through RNA seq
      data analysis of developing spikes of finger millet (Eleusine coracana):
      Deciphering the role of key genes involved in oxalate formation in relation to
      grain calcium accumulation.
AB  - In the present study, we identified seven major genes of oxalic acid biosynthesis
      pathway (SGAT, GGAT, ICL, GLO, MHAR, APO and OXO) from developing spike
      transcriptome of finger millet using rice as a reference. Sequence alignment of
      identified genes showed high similarity with their respective homolog in rice
      except for OXO and GLO. Transcript abundance (FPKM) reflects the higher
      accumulation of identified genes in GP-1 (low calcium genotype) as compared to GP
      45 (high calcium genotype) which was further confirmed by qRT-PCR analysis,
      indicating differential oxalate formation in both genotypes. Determination of
      oxalic acid and tartaric acid content in developing spikes explain that higher
      oxalic acid content in GP-1 however, tartaric acid content was more in GP-45.
      Higher calcium content in GP-45 and lower oxalate accumulation may be due to the
      diversion of more ascorbic acid into tartaric acid and may correspond to less
      formation of calcium oxalate. Our results suggest that more than one pathway for
      oxalic acid biosynthesis might be present in finger millet with probable
      predominance of ascorbate-tartarate pathway rather than glyoxalate-oxalate
      conversion. Thus, finger millet can be use as an excellent model system for
      understanding more specific role of nutrients-antinutrients interactions, as
      evident from the present study.

PMID- 29459010
TI  - Plasma microRNA signature of patients with IgA nephropathy.
AB  - We looked for differentially expressed MicroRNAs (miRNAs) in Immunoglobulin A
      nephropathy (IgAN). Forty-eight miRNAs were identified through the initial
      screening phase (2 IgAN pools vs. 1 normal control (NC) pool) using quantitative
      reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel
      (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M). By qRT-PCR, these miRNAs were
      further assessed in the training (32 IgAN VS. 31 NCs) and testing stages (51 IgAN
      VS. 51 NCs). The renal pathological lesions of patients with IgAN were evaluated
      according to Lee's grading system. We discovered a plasma miRNA signature
      including four up-regulated miRNAs (miR-148a-3p, miR-150-5p, miR-20a-5p and miR
      425-3p) and the areas under the receiver operating characteristic (ROC) curve
      (AUC) were 0.80 and 0.76 for the training and testing stage, respectively. The
      expression of the four miRNAs in IgAN grade I-II subgroups (according to Lee's
      grading system) was obviously higher than that in IgAN grade III-V (P < .05). In
      summary, the plasma expression of miR-148a-3p, miR-150-5p, miR-20a-5p and miR-425
      3p were up-regulated in patients with IgAN, especially the early-stage disease.
      Further studies are needed to explore the roles of the four miRNAs in the
      pathogenesis and progression of IgAN.

PMID- 29459011
TI  - The effect of neoadjuvant chemotherapy on the correlation of tumor-associated
      macrophages with CD31 and LYVE-1.
AB  - Angiogenesis and lymphangiogenesis play a crucial role in tumor growth, invasion
      and metastasis. Tumor-associated macrophages (TAM) induce both angiogenesis and
      lymphangiogenesis in mouse breast cancer models and positively correlate with
      these processes in human breast cancer patients. Neoadjuvant chemotherapy (NAC)
      is a widely used therapeutic option for cancer treatment. However, the effect of
      NAC on the distribution of TAM within intratumoral compartments and their
      correlation with angiogenesis and lymphangiogenesis remained unknown. In the
      present study we analyzed the effect of NAC on the distribution of CD68+ and
      stabilin-1+ TAM in five functionally distinct areas of human breast cancer and
      their correlations with microvessel density (MVD) and lymphatic microvessel
      density (LMVD), identified by CD31 and LYVE1, respectively. We found that NAC
      enhances blood vessel density in soft fibrous stroma and in coarse fibrous
      stroma. Without NAC the amount of CD68+ TAM in gaps of ductal tumor structures
      positively correlate with CD31+ microvessel density in soft fibrous stroma. NAC
      had enhancing effect on the amount of CD68+ TAM but not stabilin-1+ TAM in soft
      fibrous stroma. However, no correlation between TAM and CD31+ microvessel density
      was identified after NAC. NAC did not enhance the lymphatic microvessel density.
      But after NAC stabilin-1 expressing subpopulation of TAM positively correlated
      with expression of LYVE-1. We hypothesized that CD68+ TAM can support tumor
      angiogenesis primarily before NAC, while stabilin-1+ TAM can contribute to the
      maintenance of lymphatic microvessel density after NAC.

PMID- 29459012
TI  - Forensic DNA phenotyping legislation cannot be based on "Ideal FDP"-A response to
      Caliebe, Krawczak and Kayser (2017).

PMID- 29459013
TI  - The family Coriobacteriaceae is a potential contributor to the beneficial effects
      of Roux-en-Y gastric bypass on type 2 diabetes.
AB  - BACKGROUND: Changes in gut microbiota induced by bariatric surgery have been
      associated with metabolic benefits. OBJECTIVES: Our aim was to identify specific
      gut microbiota that may contribute to the improvement of type 2 diabetes (T2D)
      after Roux-en-Y gastric bypass (RYGB). SETTING: Laboratories of Shanghai Diabetes
      Institute and Shanghai Sixth People's Hospital. METHODS: Diabetic rats induced
      via a high-fat diet and low-dose streptozotocin administration were randomized to
      RYGB or sham surgery, and stool samples were collected at baseline and at
      postoperative week 8. The fecal microbiota was profiled using 16S ribosomal RNA
      gene sequencing. Additionally, we performed a case-control study of the gut
      microbial community profiles of T2D patients compared with those of healthy
      individuals via 16S ribosomal RNA gene sequencing of mucosal-luminal interface
      samples collected from the ascending colon during colonoscopy. RESULTS: RYGB
      significantly reduced the weight and improved glucose tolerance and insulin
      sensitivity in diabetic rats. Principal coordinate analysis showed that RYGB
      caused marked alterations in the gut microbiota. The RYGB group was
      postoperatively enriched for Bacteroidetes, Proteobacteria, Fusobacteria, and
      Actinobacteria, whereas the sham surgery group was enriched for Firmicutes and
      Verrucomicrobia. Based on the gut microbial patterns in the T2D patients, we
      found that the family Coriobacteriaceae within Actinobacteria might contribute to
      the beneficial effects of RYGB on T2D. CONCLUSIONS: RYGB significantly improves
      glucose metabolism and alters the gut microbiota. Moreover, the family
      Coriobacteriaceae may partly mediate the beneficial effects of RYGB on T2D and
      thus possibly contribute to the development of novel bacteria-based therapeutic
      approaches.

PMID- 29459016
TI  - Special issue: Late consequences of venous thromboembolism.

PMID- 29459015
TI  - Endovascular interventions decrease length of hospitalization and are cost
      effective in acute mesenteric ischemia.
AB  - OBJECTIVE: Acute mesenteric ischemia (AMI) continues to be one of the most
      devastating diagnoses requiring emergent vascular intervention. There is a
      national trend toward increased use of endovascular procedures, with improved
      survival for the treatment of these patients. Our aim was to evaluate whether
      this trend has changed the treatment of AMI and the subsequent impact on length
      of hospitalization and hospitalization costs. METHODS: We identified all patients
      admitted for AMI from the National Inpatient Sample from 2004 to 2014 who
      received open surgical revascularization (OPEN) or an endovascular intervention
      (ENDO). Primary end points included length of hospital stay and cost of
      hospitalization. Our secondary end points included acute kidney injury (AKI), in
      hospital mortality, and routine discharge. RESULTS: Among 10,381 discharges
      identified in the data set, 3833 (37%; 97.5% confidence interval [CI], 35%-39%)
      were male patients with a mean age of 69 years (range, 18-98 years); 4543 (44%;
      97.5% CI, 41%-47%) patients were treated ENDO, and 5839 (56%; 97.5% CI, 53%-59%)
      patients were treated OPEN. Although a higher proportion of patients in the ENDO
      group (28%; 97.5% CI, 24%-31%) vs the OPEN group (14%; 97.5% CI, 11%-16%) had a
      moderate to severe Charlson Comorbidity Index (P < .0001), ENDO was associated
      with a lower mortality rate (12.3% [97.5% CI, 9.8%-14.8%] vs 33.1% [97.5% CI,
      29.9%-36.2%]; P < .0001) and a lower mean hospitalization cost ($41,615 [97.5%
      CI, $38,663-$44,567] vs $60,286 [97.5% CI, $56,736-$63,836]; P < .0001). After
      propensity-adjusted logistic regression analysis, OPEN retained a significant
      association with higher mortality than ENDO (odds ratio, 3.0; 97.5% CI, 2.2-4.1)
      and with higher costs (mean, $9196; 97.5% CI, $3797-$14,595). Patients in the
      OPEN group had higher risk for AKI (P < .0001) and discharge to a skilled nursing
      facility (P < .0001) rather than home. CONCLUSIONS: Although the rate of ENDO
      continues to rise nationally, it still has not surpassed OPEN revascularization
      in the face of AMI. Patients treated endovascularly demonstrated one-third the
      rate of in-hospital mortality (odds ratio, 3.0; 97.5% CI, 2.2-4.1), an increased
      hazard ratio for discharge alive (hazard ratio, 2.27; 97.5% CI, 2.00-2.58), and a
      cost saving of $9196 (97.5% CI, $3797-$14,595) per hospitalization. Furthermore,
      they were less likely to develop AKI and to be discharged home after
      hospitalization.

PMID- 29459014
TI  - Regional variation in racial disparities among patients with peripheral artery
      disease.
AB  - OBJECTIVE: Prior studies identified significant racial disparities as well as
      regional variation in outcomes of patients with peripheral artery disease (PAD).
      We aimed to determine whether regional variation contributes to these racial
      disparities. METHODS: We identified all white or black patients who underwent
      infrainguinal revascularization or amputation in 15 deidentified regions of the
      Vascular Quality Initiative between 2003 and 2017. We excluded three regions with
      <100 procedures. We used multivariable linear regression, allowing clustering at
      the hospital level to calculate the marginal effects of race and region on
      adjusted 30-day mortality, major adverse limb events (MALEs), and amputation. We
      compared long-term outcomes between black and white patients within each region
      and within patients of each race treated in different regions using multivariable
      Cox regression. RESULTS: We identified 90,418 patients, 15,527 (17%) of whom were
      black. Patients underwent 31,263 bypasses, 52,462 endovascular interventions, and
      6693 amputations. Black patients were younger and less likely to smoke, to have
      coronary artery disease, or to have chronic obstructive pulmonary disease, but
      they were more likely to have diabetes, limb-threatening ischemia, dialysis
      dependence, and hypertension and to be self-insured or on Medicaid (all P < .05).
      Adjusted 30-day mortality ranged from 1.2% to 2.1% across regions for white
      patients and 0% to 3.0% for black patients; adjusted 30-day MALE varied from 4.0%
      to 8.3% for white patients and 2.4% to 8.1% for black patients; and adjusted 30
      day amputation rates varied from 0.3% to 1.2% for white patients and 0% to 2.1%
      for black patients. Black patients experienced significantly different (both
      higher and lower) adjusted rates of 30-day mortality and amputation than white
      patients did in several regions (P < .05) but not MALEs. In addition, within each
      racial group, we found significant variation in the adjusted rates of all
      outcomes between regions (all P < .01). In adjusted analyses, compared with white
      patients, black patients experienced consistently lower long-term mortality
      (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.73-0.88; P < .001) and
      higher rates of MALEs (HR, 1.15; 95% CI, 1.06-1.25; P < .001) and amputation (HR,
      1.33; 95% CI, 1.18-1.51; P < .001), with no statistically significant variation
      across the regions. However, rates of all long-term outcomes varied within both
      racial groups across regions. CONCLUSIONS: Significant racial disparities exist
      in outcomes after lower extremity procedures in patients with PAD, with regional
      variation contributing to perioperative but not long-term outcome disparities.
      Underperforming regions should use these data to generate quality improvement
      projects, as understanding the etiology of these disparities is critical to
      improving the care of all patients with PAD.

PMID- 29459017
TI  - Poor performance in incremental shuttle walk and cardiopulmonary exercise testing
      predicts poor overall survival for patients undergoing esophago-gastric
      resection.
AB  - INTRODUCTION: Esophageal and gastric cancer have a poor prognosis and surgical
      intervention is associated with considerable morbidity, highlighting the need for
      careful preoperative assessment. The Incremental Shuttle Walk Test (ISWT) and
      Cardiopulmonary exercise testing (CPET) can assess preoperative fitness. This
      study aims to investigate their correlation with both postoperative respiratory
      complications and overall survival. PATIENTS AND METHODS: Patients were
      identified who underwent esophageal or gastric resections for cancer between 2010
      and 2014 and had ISWT and/or CPET assessments. Tumor differentiation, stage,
      postoperative respiratory complications, and outcome were documented and then
      correlated with the results of the preoperative fitness assessments. RESULTS:
      Neither the ISWT result, anaerobic threshold (AT) nor VO2 Max correlated well
      with perioperative complications. However, ISWT (p < 0.001), AT (p < 0.001) and
      VO2 Max (p < 0.001) all correlated strongly with overall survival. No patient
      with a score of less than 350 m on ISWT survived beyond 3 years. In a subset of
      patients with ISWT results both pre and post chemotherapy (n = 49), those that
      had an improvement in result had a 19% incidence of post-operative respiratory
      complications compared to 45% where the result did not change or declined, though
      due to small numbers this only approached significance (p = 0.08). CONCLUSION:
      ISWT and CPET can be useful preoperative tools to predict overall survival for
      patients undergoing esophago-gastric resection. Furthermore, patients that
      improve their functional status during chemotherapy seem to do better than those
      where it remains static or declines.

PMID- 29459018
TI  - Prognostic significance of 18F-FDG PET/CT in patients with colorectal cancer
      liver metastases after hepatectomy.
AB  - INTRODUCTION: Colorectal cancer liver metastasis (CRLM) can be cured with
      surgery. To improve survival, optimal selection of CRLM patients should be done
      cautiously, which may be facilitated by preoperative [F-18] fluorodeoxyglucose
      positron emission tomography/computed tomography (18F-FDG PET/CT). METHODS: A
      total of 245 patients with CRLM between February 2007 and January 2015 were
      retrospectively studied. All clinical variables, pathological data, and various
      PET/CT parameters were correlated with disease-free survival (DFS) and overall
      survival (OS). Metastatic tumor maximum standardized uptake value (SUVmax) and
      normal liver mean SUV (SUVmean) ratio was selected for group classification.
      RESULTS: The median DFS in months were 24.5 months and median OS were 41.7
      months. Multivariate analysis found an increased risk of worse prognosis in DFS
      for primary colon cancer T3~T4, N2 stage, neoadjuvant chemotherapy, synchronous
      metastasis, multiple metastatic tumor number and metastatic tumor SUVmax/normal
      liver SUVmean ratio >4.3. The DFS rate of each group classified by SUV ratio was
      58.1%, 39.0%, and 33.6% vs. 39.3%, 20.8%, and 15.8% at 1, 3, and 5 years (p =
      0.017). Patients with multiple tumors and SUV ratio of >4.3 showed worst survival
      (OS rate: 74.2%, 41.5%, and 24.2%, p = 0.001 at 1, 3, and 5 years, respectively).
      CONCLUSIONS: PET/CT variables can be a valuable prognostic factor in patients
      with CRLM for the prediction of recurrence. Preoperative PET/CT may improve risk
      stratification and optimize outcomes of patients with CRLM.

PMID- 29459019
TI  - Real-time continuous glucose monitoring in adults with type 1 diabetes and
      impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple
      daily insulin injections (HypoDE): a multicentre, randomised controlled trial.
AB  - BACKGROUND: The effectiveness of real-time continuous glucose monitoring (rtCGM)
      in avoidance of hypoglycaemia among high-risk individuals with type 1 diabetes
      treated with multiple daily insulin injections (MDI) is unknown. We aimed to
      ascertain whether the incidence and severity of hypoglycaemia can be reduced
      through use of rtCGM in these individuals. METHODS: The HypoDE study was a 6
      month, multicentre, open-label, parallel, randomised controlled trial done at 12
      diabetes practices in Germany. Eligible participants had type 1 diabetes and a
      history of impaired hypoglycaemia awareness or severe hypoglycaemia during the
      previous year. All participants wore a masked rtCGM system for 28 days and were
      then randomly assigned to 26 weeks of unmasked rtCGM (Dexcom G5 Mobile system) or
      to the control group (continuing with self-monitoring of blood glucose). Block
      randomisation with 1:1 allocation was done centrally, with the study site as the
      stratifying variable. Masking of participants and study sites was not possible.
      Control participants wore a masked rtCGM system during the follow-up phase (weeks
      22-26). The primary outcome was the baseline-adjusted number of hypoglycaemic
      events (defined as glucose <=3.0 mmol/L for >=20 min) during the follow-up phase.
      The full dataset analysis comprised participants who wore the rtCGM system during
      the baseline and follow-up phases. The intention-to-treat analysis comprised all
      randomised participants. This trial is registered with ClinicalTrials.gov, number
      NCT02671968. FINDINGS: Between March 4, 2016, and Jan 12, 2017, 149 participants
      were randomly assigned (n=74 to the control group; n=75 to the rtCGM group) and
      141 completed the follow-up phase (n=66 in the control group, n=75 in the rtCGM
      group). The mean number of hypoglycaemic events per 28 days among participants in
      the rtCGM group was reduced from 10.8 (SD 10.0) to 3.5 (4.7); reductions among
      control participants were negligible (from 14.4 [12.4] to 13.7 [11.6]). Incidence
      of hypoglycaemic events decreased by 72% for participants in the rtCGM group
      (incidence rate ratio 0.28 [95% CI 0.20-0.39], p<0.0001). 18 serious adverse
      events were reported: seven in the control group, ten in the rtCGM group, and one
      before randomisation. No event was considered to be related to the
      investigational device. INTERPRETATION: Usage of rtCGM reduced the number of
      hypoglycaemic events in individuals with type 1 diabetes treated by MDI and with
      impaired hypoglycaemia awareness or severe hypoglycaemia. FUNDING: Dexcom Inc.

PMID- 29459020
TI  - Time for use of mesh repair for all umbilical hernias?

PMID- 29459022
TI  - Continuous glucose monitoring: transforming diabetes management step by step.

PMID- 29459021
TI  - Mesh versus suture repair of umbilical hernia in adults: a randomised, double
      blind, controlled, multicentre trial.
AB  - BACKGROUND: Both mesh and suture repair are used for the treatment of umbilical
      hernias, but for smaller umbilical hernias (diameter 1-4 cm) there is little
      evidence whether mesh repair would be beneficial. In this study we aimed to
      investigate whether use of a mesh was better in reducing recurrence compared with
      suture repair for smaller umbilical hernias. METHODS: We did a randomised, double
      blind, controlled multicentre trial in 12 hospitals (nine in the Netherlands, two
      in Germany, and one in Italy). Eligible participants were adults aged at least 18
      years with a primary umbilical hernia of diameter 1-4 cm, and were randomly
      assigned (1:1) intraoperatively to either suture repair or mesh repair. In the
      first 3 years of the inclusion period, blocked randomisation (of non-specified
      size) was achieved by an envelope randomisation system; after this time computer
      generated randomisation was introduced. Patients, investigators, and analysts
      were masked to the allocated treatment, and participants were stratified by
      hernia size (1-2 cm and >2-4 cm). At study initiation, all surgeons were invited
      to training sessions to ensure they used the same standardised techniques for
      suture repair or mesh repair. Patients underwent physical examinations at 2
      weeks, and 3, 12, and 24-30 months after the operation. The primary outcome was
      the rate of recurrences of the umbilical hernia after 24 months assessed in the
      modified intention-to-treat population by physical examination and, in case of
      any doubt, abdominal ultrasound. This trial is registered with
      ClinicalTrials.gov, number NCT00789230. FINDINGS: Between June 21, 2006, and
      April 16, 2014, we randomly assigned 300 patients, 150 to mesh repair and 150 to
      suture repair. The median follow-up was 25.1 months (IQR 15.5-33.4). After a
      maximum follow-up of 30 months, there were fewer recurrences in the mesh group
      than in the suture group (six [4%] in 146 patients vs 17 [12%] in 138 patients; 2
      year actuarial estimates of recurrence 3.6% [95% CI 1.4-9.4] vs 11.4% (6.8-18.9);
      p=0.01, hazard ratio 0.31, 95% CI 0.12-0.80, corresponding to a number needed to
      treat of 12.8). The most common postoperative complications were seroma (one
      [<1%] in the suture group vs five [3%] in the mesh group), haematoma (two [1%] vs
      three [2%]), and wound infection (one [<1%] vs three [2%]). There were no
      anaesthetic complications or postoperative deaths. INTERPRETATION: This is the
      first study showing high level evidence for mesh repair in patients with small
      hernias of diameter 1-4 cm. Hence we suggest mesh repair should be used for
      operations on all patients with an umbilical hernia of this size. FUNDING:
      Department of Surgery, Erasmus University Medical Center, Rotterdam, Netherlands.

PMID- 29459023
TI  - Focusing on long non-coding RNA dysregulation in newly diagnosed multiple
      myeloma.
AB  - AIMS: Multiple myeloma (MM) is an incurable hematological cancer with a higher
      rate of relapse. Alterations in the function of long non-coding RNAs (lncRNAs)
      promote the progression and metastasis of cancer. We carry out this study to
      explore the expression profile of differently expressed lncRNAs in newly
      diagnosed MM. MAIN METHODS: The Bone marrows we analyzed were obtained from five
      MM and five IDA patients (serving as controls). Arraystar Human LncRNA Array V4.0
      was used to profile expression of lncRNAs and mRNAs. Gene ontology (GO) and
      pathway analysis were utilized to understand the biological roles of differently
      expressed genes, while Database for Annotation, Visualization and Integrated
      Discovery (DAVID) was used for constructing the lncRNA-mRNA co-expression
      network. Quantitative polymerase chain reaction (qRT-PCR) was performed to
      confirm the expressions of dysregulated lncRNAs. KEY FINDINGS: Bioinformatic
      analysis of the lncRNA expression identified >3000 dysregulated lncRNAs
      (difference >= 2-fold) in MM samples. GO and pathway analysis revealed that ECM
      receptor and cell cycle pathway-related genes were significantly associated with
      MM. Four dysregulated lncRNAs were confirmed by qRT-PCR. Among them, the
      expression of ST3GAL6-AS1, LAMA5-AS1and RP11-175D17.3wereassociated with stage
      and risk status of MM. On the basis of GEO public database analysis, LAMA5-AS1
      was related with an overall survival rate of MM patients. SIGNIFICANCE: These
      results reveal the feasible functions of lncRNAs in pathogenesis of MM. Further
      studies are required to explore whether these lncRNAs could serve as candidate
      therapeutic targets and new molecular biomarkers for MM.

PMID- 29459024
TI  - Effect of baicalin on GLUT4 expression and glucose uptake in myotubes of rats.
AB  - AIMS: Although baicalin could attenuate obesity-induced insulin resistance, the
      detailed mechanism of baicalin on glucose uptake has not been sufficiently
      explored as yet. The aim of this study was to survey if baicalin might facilitate
      glucose uptake and to explore its signal mechanisms in L6 myotubes. MATERIALS AND
      METHODS: L6 myotubes were treated with 100, 200, 400 MUM baicalin for 6 h, 12 h
      and 24 h in this study. Then 2-NBDG and insulin signal protein levels in myotubes
      of L6 cells were examined. KEY FINDINGS: We discovered that administration of
      baicalin enhanced GLUT4, PGC-1alpha, pP38MAPK, pAKT and pAS160 contents, as well
      as GLUT4 mRNA and PGC-1alpha mRNA levels in L6 myotubes. The beneficial metabolic
      changes elicited by baicalin were abrogated in myotubes of L6 by P38MAPK or AKT
      inhibitors. SIGNIFICANCE: These results suggest that baicalin promoted glucose
      uptake in myotubes by differential regulation on P38MAPK and AKT activity. In
      conclusion, these data provide insight that baicalin is a powerful and promising
      agent for the treament of hyperglycemia via AKT/AS160/GLUT4 and
      P38MAPK/PGC1alpha/GLUT4 pathway.

PMID- 29459025
TI  - Identification of forest cutting in managed forest of Haldwani, India using ALOS
      2/PALSAR-2 SAR data.
AB  - Large-scale forest clear-cut identification is one of the major application of
      remote sensing techniques. ALOS-2/PALSAR-2 is the latest SAR satellite providing
      multi-polarized L-band SAR data. With increasing deforestation, it is important
      to assess the potential of SAR data for identifying clear-cuts in forest regions.
      In this research work, multi-temporal ALOS-2/PALSAR-2 SAR data and supplementary
      Landsat-8 optical data sets are acquired over Indian tropical forest, and SAR
      parameters are analysed over a progressively clear-cut Teak plantation.
      Sensitivity of the SAR parameters to progressive clear-cuts is estimated and
      found that the cross-polarized backscatter sigmaHV0 and entropy parameter H are
      most sensitive to both partial and complete clear-cut in forest compartments. An
      entropy thresholding based classification is carried out to identify clear-cut
      regions with a good accuracy. The study highlights the utility of SAR parameters
      to monitor forest clear-cuts for better forest management.

PMID- 29459026
TI  - Prevalence and Risk of Protein-Energy Wasting Assessed by Subjective Global
      Assessment in Older Adults With Advanced Chronic Kidney Disease: Results From the
      EQUAL Study.
AB  - OBJECTIVES: Prevalence and risk factors for protein-energy wasting (PEW) are
      poorly studied in the nondialysis, older population with advanced chronic kidney
      disease (CKD). Our aim was to evaluate the prevalence of PEW in advanced stage
      CKD patients aged greater than 65 years. Furthermore, we aimed to describe risk
      factors for PEW in the overall study population and among obese individuals.
      DESIGN: Prospective observational cohort study. METHODS: The EQUAL study, a
      European Quality Study on treatment in advanced chronic kidney disease, is a
      multicenter prospective observational cohort study in six European countries. We
      included patients aged >=65 years with incident glomerular filtration rate
      <20mL/min/1.73m2 not on dialysis attending nephrology care. PEW was assessed by 7
      point Subjective Global Assessment (7-p SGA). RESULTS: In general, the study
      cohort (n = 1,334) was overweight (mean body mass index [BMI] 28.4 kg/m2). The
      majority of the patients had a normal nutritional status (SGA 6-7), 26% had
      moderate PEW (SGA 3-5), and less than 1% had severe PEW (SGA 1-2). Muscle wasting
      and loss of fat tissue were the most frequent alterations according to the SGA
      subscales, especially in those aged >80 years. The prevalence of PEW was higher
      among women, increased with age, and was higher in those with
      depression/dementia. PEW was the most common in those with underweight (BMI <22
      kg/m2), 55% or normal weight (BMI 22-25 kg/m2), 40%. In obese individuals (BMI
      >30 kg/m2), 25% were diagnosed with protein wasting. Risk factors for SGA <=5 in
      obese people were similar to those for the overall study population. CONCLUSION:
      This European multicenter study shows that the prevalence of PEW is high in
      patients with advanced CKD aged >65 years. The risk of PEW increases
      substantially with age and is commonly characterized by muscle wasting. Our study
      suggests that focus on nutrition should start early in the follow-up of older
      adults with CKD.

PMID- 29459027
TI  - Aortic smooth muscle cells and myocardial infarction: Does the ascending aorta
      feel a heart attack?

PMID- 29459029
TI  - Targeting the Architecture of Deregulated Protein Complexes in Cancer.
AB  - The architectures of central signaling hubs are precisely organized by static and
      dynamic protein-protein interactions (PPIs). Upon deregulation, these PPI
      platforms are capable to propagate or initiate pathophysiological signaling
      events. This causes the acquisition of molecular features contributing to the
      etiology or progression of many diseases, including cancer, where deregulated
      molecular interactions of signaling proteins have been best studied. The reasons
      for PPI-dependent reprogramming of cancer-initiating cells are manifold; in many
      cases, mutations perturb PPIs, enzyme activities, protein abundance, or protein
      localization. Consequently, the pharmaceutical targeting of PPIs promises to be
      of remarkable therapeutic value. For this review we have selected three key
      players of oncogenic signaling which are differently affected by PPI
      deregulation: two (the small G proteins of the RAS family and the transcription
      factor MYC) are considered "undruggable" using classical drug discovery
      approaches and in the case of the third protein discussed here, PKA, standard
      kinase inhibitors, may be unsuitable in the clinic. These circumstances require
      alternative strategies, which may lie in pharmaceutical drug interference of
      critical PPIs accountable for oncogenic signaling.

PMID- 29459030
TI  - Multifaceted Nucleolin Protein and Its Molecular Partners in Oncogenesis.
AB  - Discovered in 1973, nucleolin is one of the most abundant phosphoproteins of the
      nucleolus. The ability of nucleolin to be involved in many cellular processes is
      probably related to its structural organization and its capability to form many
      different interactions with other proteins. Many functions of nucleolin affect
      cellular processes involved in oncogenesis-for instance: in ribosome biogenesis;
      in DNA repair, remodeling, and genome stability; in cell division and cell
      survival; in chemokine and growth factor signaling pathways; in angiogenesis and
      lymphangiogenesis; in epithelial-mesenchymal transition; and in stemness. In this
      review, we will describe the different functions of nucleolin in oncogenesis
      through its interaction with other proteins.

PMID- 29459031
TI  - Subcellular Targeting of Nitric Oxide Synthases Mediated by Their N-Terminal
      Motifs.
AB  - From a catalytic point of view, the three mammalian nitric oxide synthases (NOSs)
      function in an almost identical way. The N-terminal oxygenase domain catalyzes
      the conversion of l-arginine to l-citrulline plus .NO in two sequential oxidation
      steps. Once l-arginine binds to the active site positioned above the heme moiety,
      two consecutive monooxygenation reactions take place. In the first step, l
      arginine is hydroxylated to make Nomega-hydroxy-l-arginine in a process that
      requires 1 molecule of NADPH and 1 molecule of O2 per mol of l-arginine reacted.
      In the second step, Nomega-hydroxy-l-arginine, never leaving the active site, is
      oxidized to .NO plus l-citrulline and 1 molecule of O2 and 0.5 molecules of NADPH
      are consumed. Since nitric oxide is an important signaling molecule that
      participates in a number of biological processes, including neurotransmission,
      vasodilation, and immune response, synthesis and release of .NO in vivo must be
      exquisitely regulated both in time and in space. Hence, NOSs have evolved
      introducing in their amino acid sequences subcellular targeting motifs, most of
      them located at their N-termini. Deletion studies performed on recombinant,
      purified NOSs have revealed that part of the N-terminus of all three NOS can be
      eliminated with the resulting mutant enzymes still being catalytically active.
      Likewise, NOS isoforms lacking part of their N-terminus when transfected in cells
      render mislocalized, active proteins. In this review we will comment on the
      current knowledge of these subcellular targeting signals present in nNOS, iNOS,
      and eNOS.

PMID- 29459028
TI  - Homo- and Heterodimerization of Proteins in Cell Signaling: Inhibition and Drug
      Design.
AB  - Protein dimerization controls many physiological processes in the body. Proteins
      form homo-, hetero-, or oligomerization in the cellular environment to regulate
      the cellular processes. Any deregulation of these processes may result in a
      disease state. Protein-protein interactions (PPIs) can be inhibited by
      antibodies, small molecules, or peptides, and inhibition of PPI has therapeutic
      value. PPI drug discovery research has steadily increased in the last decade, and
      a few PPI inhibitors have already reached the pharmaceutical market. Several PPI
      inhibitors are in clinical trials. With advancements in structural and molecular
      biology methods, several methods are now available to study protein homo- and
      heterodimerization and their inhibition by drug-like molecules. Recently
      developed methods to study PPI such as proximity ligation assay and enzyme
      fragment complementation assay that detect the PPI in the cellular environment
      are described with examples. At present, the methods used to design PPI
      inhibitors can be classified into three major groups: (1) structure-based drug
      design, (2) high-throughput screening, and (3) fragment-based drug design. In
      this chapter, we have described some of the experimental methods to study PPIs
      and their inhibition. Examples of homo- and heterodimers of proteins, their
      structural and functional aspects, and some of the inhibitors that have clinical
      importance are discussed. The design of PPI inhibitors of epidermal growth factor
      receptor heterodimers and CD2-CD58 is discussed in detail.

PMID- 29459033
TI  - Defining Pharmacological Targets by Analysis of Virus-Host Protein Interactions.
AB  - Viruses are obligate parasites that depend on cellular factors for replication.
      Pharmacological inhibition of essential viral proteins, mostly enzymes, is an
      effective therapeutic alternative in the absence of effective vaccines. However,
      this strategy commonly encounters drug resistance mechanisms that allow these
      pathogens to evade control. Due to the dependency on host factors for viral
      replication, pharmacological disruption of the host-pathogen protein-protein
      interactions (PPIs) is an important therapeutic alternative to block viral
      replication. In this review we discuss salient aspects of PPIs implicated in
      viral replication and advances in the development of small molecules that inhibit
      viral replication through antagonism of these interactions.

PMID- 29459034
TI  - Investigating the Influence of Hotspot Mutations in Protein-Protein Interaction
      of IDH1 Homodimer Protein: A Computational Approach.
AB  - Protein-protein interaction (PPI) helps in maintaining the cellular homeostasis.
      In particular, the homodimeric proteins play a crucial role as cell regulators.
      Studying the critical functions of each PPI on the living system is very
      challenging. The mutations in the PPIs have given birth to various diseases
      including many types of cancers and it has soon become the target for drug
      discovery. The mutations in IDH1, an asymmetric homodimer in the cytoplasm, leads
      to various diseases including gliomas. In this study, we have used extensive
      computational approaches to identify the impact of missense mutations (R132C,
      R132G, R132H, R132L, R132S, and V178I) occurring in the interacting region of the
      IDH1 homodimer. By in silico pathogenicity analysis, all the mutations occurring
      at the positions 132 and 178 were found to be pathogenic and neutral
      respectively. Furthermore, the mutants R132C and R132G were found to be
      responsible for increasing the stability, whereas the mutants R132H, R132L, and
      R132S were found to be responsible for the decrease in stability by stability
      analysis. R132H, R132L, and R132S mutants exhibited higher destabilization when
      compared to the structures of R132C and R132G mutants by molecular docking and
      molecular dynamics analysis.

PMID- 29459032
TI  - Development of Protein-Protein Interaction Inhibitors for the Treatment of
      Infectious Diseases.
AB  - Protein-protein interaction (PPI) inhibitors are a rapidly expanding class of
      therapeutics. Recent advances in our understanding of PPIs and success of early
      examples of PPI inhibitors demonstrate the feasibility of targeting PPIs. This
      review summarizes the techniques used for the discovery and optimization of a
      diverse set PPI inhibitors, focusing on the development of PPI inhibitors as new
      antibacterial and antiviral agents. We close with a summary of the advances
      responsible for making PPI inhibitors realistic targets for therapeutic
      intervention and brief outlook of the field.

PMID- 29459035
TI  - Human Interactomics: Comparative Analysis of Different Protein Interaction
      Resources and Construction of a Cancer Protein-Drug Bipartite Network.
AB  - Unraveling the protein interaction wiring that occurs in human cells as a
      scaffold of biological processes requires the identification of all elements that
      constitute such molecular interaction networks. Proteome-wide experimental
      studies and bioinformatic comprehensive efforts have provided reliable and
      updated compendiums of the human protein interactome. In this work, we present a
      current view of available databases of human protein-protein interactions (PPIs)
      that allow building protein interaction networks. We also investigate human
      proteins as targets of specific drugs to analyze how chemicals interact with
      different target proteins, placing also the study in a network relational space.
      Hence, we undertake a description of several major drug-target resources to
      provide a present perspective of the associations between human proteins and
      specific chemicals. The identification of molecular targets for specific drugs is
      a critical step to improve disease therapy. As different diseases have different
      biomolecular scenarios, we addressed the identification of drug-targeted genes
      focusing our investigations on cancer and cancer genes. So, a description of
      resources that provide curated compendiums of human cancer genes is presented.
      Cancer is a complex disease where multiple genetic changes rewire cellular
      networks during carcinogenesis. This indicates that cancer drug therapy needs the
      implementation of network-driven studies to reveal multiplex interactions between
      cancer genes and drugs. To make progress in this direction, in the last part of
      this work we provide a bipartite network of cancer genes and their drugs shown in
      a graph landscape that disclose the existence of specific drug-target modules.

PMID- 29459036
TI  - Targeting Intramembrane Protein-Protein Interactions: Novel Therapeutic Strategy
      of Millions Years Old.
AB  - Intramembrane protein-protein interactions (PPIs) are involved in transmembrane
      signal transduction mediated by cell surface receptors and play an important role
      in health and disease. Recently, receptor-specific modulatory peptides rationally
      designed using a general platform of transmembrane signaling, the signaling chain
      homooligomerization (SCHOOL) model, have been proposed to therapeutically target
      these interactions in a variety of serious diseases with unmet needs including
      cancer, sepsis, arthritis, retinopathy, and thrombosis. These peptide drug
      candidates use ligand-independent mechanisms of action (SCHOOL mechanisms) and
      demonstrate potent efficacy in vitro and in vivo. Recent studies surprisingly
      revealed that in order to modify and/or escape the host immune response, human
      viruses use similar mechanisms and modulate cell surface receptors by targeting
      intramembrane PPIs in a ligand-independent manner. Here, I review these
      intriguing mechanistic similarities and discuss how the viral strategies
      optimized over a billion years of the coevolution of viruses and their hosts can
      help to revolutionize drug discovery science and develop new, disruptive
      therapies. Examples are given.

PMID- 29459037
TI  - Preface.

PMID- 29459038
TI  - Molecular characterization of gene regulatory networks in primary human tracheal
      and bronchial epithelial cells.
AB  - BACKGROUND: Robust methods to culture primary airway epithelial cells were
      developed several decades ago and these cells provide the model of choice to
      investigate many diseases of the human lung. However, the molecular signature of
      cells from different regions of the airway epithelium has not been well
      characterized. METHODS: We utilize DNase-seq and RNA-seq to examine the molecular
      signatures of primary cells derived from human tracheal and bronchial tissues, as
      well as healthy and diseased (cystic fibrosis (CF)) donor lung tissue. RESULTS:
      Our data reveal an airway cell signature that is divergent from other epithelial
      cell types and from common airway epithelial cell lines. The differences between
      tracheal and bronchial cells are clearly evident as are common regulatory
      features. Only minor variation is seen between bronchial cells from healthy or CF
      donors. CONCLUSIONS: These data are a valuable resource for functional genomics
      analysis of airway epithelial tissues in human disease.

PMID- 29459039
TI  - Influence of Meibomian Gland Dysfunction and Friction-Related Disease on the
      Severity of Dry Eye.
AB  - PURPOSE: To evaluate the effect of meibomian gland dysfunction (MGD) and friction
      related disease (FRD) on the severity of dry eye disease (DED). DESIGN: Cross
      sectional observational study. PARTICIPANTS: This study enrolled 449 patients
      with DED (63 men and 386 women; mean age, 62.6+/-15.7 years [range, 21-90 years])
      for analysis. METHODS: Subjective symptoms, the ocular surface, tear function,
      and the presence of MGD and FRD (superior limbic keratoconjunctivitis,
      conjunctivochalasis, and lid wiper epitheliopathy) were investigated. MAIN
      OUTCOME MEASURES: Schirmer value, tear film breakup time (TBUT), and
      keratoconjunctival score. RESULTS: We classified the participants into aqueous
      deficient dry eye (ADDE; n = 231 [51.4%]) and short TBUT dry eye subtype (TBUT
      DE; n = 109 [24.3%]) subgroups. The TBUT was shorter in patients with MGD than in
      those without MGD, whereas other ocular signs showed no difference (TBUT: MGD
      present, 1.97+/-1.02 seconds; MGD absent, 2.94+/-1.63 seconds [P < 0.001];
      ADDE/MGD present, 1.94+/-1.08 seconds; ADDE/MGD absent, 2.77+/-1.61 seconds [P <
      0.001]; short TBUT-DE/MGD present, 2.07+/-0.97 seconds; short TBUT-DE/MGD absent,
      2.94+/-1.23 seconds [P = 0.01]). The ADDE patients with FRD showed a worse TBUT
      than ADDE patients without FRD (TBUT: ADDE/FRD present, 2.08+/-1.39 seconds;
      ADDE/FRD absent, 2.92+/-1.54 seconds; P < 0.001). CONCLUSIONS: This study showed
      associations between MGD, FRD, or both and ocular signs in DED. In the presence
      of MGD, FRD, or both, TBUT was significantly shortened regardless of the dry eye
      status or subtype.

PMID- 29459040
TI  - Interocular Axial Length and Corneal Power Differences as Predictors of
      Postoperative Refractive Outcomes after Cataract Surgery.
AB  - PURPOSE: To determine whether differences between eyes in axial length (AL) and
      corneal power (K) on optical biometry are predictive of refractive outcomes.
      DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 729 patients (1458
      eyes) who underwent bilateral phacoemulsification at TLC (Mississauga, Ontario,
      Canada) from September 2013 to August 2015. METHODS: We compared the proportion
      of patients having >0.5 diopters (D) of refractive error from target stratified
      by interocular axial length differences (IALDs) and interocular K differences
      (IKDs) between eyes as measured by optical biometry (IOL-Master, Carl Zeiss
      Meditec, Oberkochen, Germany). Analysis was repeated for 0.25 D or 1.0 D targets
      and for patients with uncorrected visual acuity (UCVA) >0.3 logarithm of the
      minimum angle of resolution (logMAR) postoperatively. MAIN OUTCOME MEASURES:
      Proportions, odds ratios (ORs), and corresponding 95% confidence intervals (CIs)
      were computed using generalized estimating equations to account for within
      patient correlation. RESULTS: Some 79.1% of eyes were <=0.5 D of refractive
      target, 47.0% were <=0.25 D, and 97.2% were <=1.0 D. The OR of having a
      refractive outcome >0.5 D from target for IALD cutoff of 0.2 mm was 1.4 (1.1
      1.8), of 0.3 mm was 1.6 (1.2-2.1), and of 0.4 mm was 1.8 (1.3-2.5). This
      translates to 70.0% (63.5-75.7) within target for IALD of >=0.4 mm versus 80.7%
      (78.4-82.9) for <0.4 mm. For a given patient with IALD, the chance of being off
      target was similar for the shorter and longer eye. Eyes outside of target were
      twice as likely to be <-0.5 D than >0.5 D. Interocular K difference was largely
      not associated with prediction error, yet larger IKD-flat, steep, and average
      were associated with increased odds of UCVA >0.3 logMAR postoperatively.
      CONCLUSIONS: Interocular axial length difference of as little as >=0.2 mm is
      associated with a higher chance of >0.5 D of refractive error from target and
      worse UCVA. Interocular K difference was not associated with worse refractive
      error from target, although a difference of >=0.4 D was associated with worse
      UCVA. These cutoffs should be considered in preoperative planning and discussion
      with patients. Future study is required to assess whether repeating measurements,
      using adjunctive measurement devices, or attempting to separate true differences
      from artifact based on preoperative refractive characteristics reduces residual
      refractive error.

PMID- 29459041
TI  - Dexamethasone Inserts in Noninfectious Uveitis: A Single-Center Experience.
AB  - PURPOSE: To report the effectiveness of repeated intravitreal dexamethasone (DEX)
      inserts in noninfectious uveitis patients. DESIGN: Prospective, single-center,
      interventional clinical trial between February 2010 and March 2015. PARTICIPANTS:
      Patients with noninfectious uveitis with cystoid macular edema and/or vitreitis.
      METHODS: Patients were treated with a 700-MUg intravitreal DEX insert (Ozurdex;
      Allergan, Inc., Irvine, CA). Follow-up visits were scheduled 1, 3, and 6 months
      after injection. Best-corrected visual acuity (BCVA), central retinal thickness
      (CRT), vitreous haze (VH) score, intraocular pressure (IOP), and adverse events
      were recorded. MAIN OUTCOME MEASURES: Primary outcome was the reduction of CRT.
      Secondary outcome was the improvement in BCVA and reduction of VH. RESULTS: In
      total, 109 eyes of 76 patients received 298 DEX inserts. Fifty-two patients were
      women (68%). The mean age of all participants was 57 years (range, 24-88 years).
      More than 3 DEX inserts were injected into 44% of eyes. Mean number of injections
      were 1.54+/-0.5 (standard deviation [SD]), 1.98+/-0.84, and 2.46+/-1.1 over 12,
      18, and 24 months, respectively. Central retinal thickness decreased
      significantly (P < 0.001) from 465 MUm at baseline to 318, 342, and 388 MUm after
      1, 3, and 6 months, respectively. Similar trends were seen in eyes receiving a
      second, third, and fourth DEX insert. Patients with idiopathic uveitis and
      sarcoidosis benefited well from DEX inserts. The greatest overall benefit was
      achieved in patients with no systemic treatment and patients receiving
      antimetabolites and cyclosporin A. A significant VH score reduction was
      documented in 44% of eyes after 1 month. A gain of more than 3 lines in BCVA was
      recorded in 31% to 37%, 26% to 39%, and 8% to 32% of eyes after 1, 3, and 6
      months, respectively. A transient rise in mean IOP after 1 month (P < 0.001) and
      after 3 months (P = 0.001) was seen. CONCLUSIONS: The repeated longer-term
      administration of DEX inserts in noninfectious uveitis patients, either alone or
      in combination with other therapies, led to improved CRT, BCVA, and VH.
      Underlying diseases and concomitant systemic therapy seem to have an impact on
      overall treatment benefit. Ocular complications were reversible and were managed
      by local treatment, with exception of cataract formation.

PMID- 29459042
TI  - Churg-Strauss syndrome with cardiac involvement: case illustration and
      contribution of CMR in the diagnosis and clinical follow-up.
AB  - This report summarises three cases of Churg-Strauss syndrome (CSS) illustrating
      the diagnostic challenges associated with the cardiac manifestation of this
      disease. Here, we illustrate the role of cardiac magnetic resonance (CMR) for
      diagnosis and follow-up of CSS with a focus on new non-contrast T2-weighted
      imaging sequences for quantification of myocardial scar tissue and quantitative
      T2 mapping techniques, which allow the detection of myocardial edema.

PMID- 29459043
TI  - Is there a best approach for extracorporeal life support cannulation: a review of
      the extracorporeal life support organization.
AB  - BACKGROUND: Neurologic complications are common, and amongst the most devastating
      complications in pediatric patients undergoing extracorporeal life support
      (ECLS). Carotid artery cannulation (CAN) has been associated with an increase in
      these complications, thereby shaping practices to avoid this approach in most
      pediatric patients in which other cannulation approaches are viable. METHODS: A
      retrospective review of children (0-18years) in the ELSO database was undertaken
      from 1989 through 2013. Multivariate logistic regression analysis of rates of
      stroke and other neurologic complications based on cannulation technique was
      undertaken, adjusting for patient factors including age, underlying disease
      process, and severity of illness. RESULTS: A total of 30,282 ECLS runs were found
      in the database. CAN was associated with higher rates of stroke (5.15% vs 3.74%)
      and overall neurologic complications. However, when correcting for patient
      factors, including age, underlying disease process, and support type, CAN was not
      associated with an increased rate of neurologic complications or stroke (p>0.05
      for both). CONCLUSION: When correcting for patient related factors CAN is not
      associated with an increase in stroke or neurologic compilcations. CAN should be
      re-examined as a cannulation technique for older pediatric patients. LEVEL OF
      EVIDENCE: III.

PMID- 29459044
TI  - Decellularized human fetal intestine as a bioscaffold for regeneration of the
      rabbit bladder submucosa.
AB  - PURPOSE: We aim to report a method to create a natural acellular scaffold from
      human fetal small intestine for augmentation cystoplasty in rabbits. METHODS:
      Fetal intestines were decellularized by immersion in a hypotonic solution. The
      success of this protocol was evaluated by histological analysis, scanning
      electron microscopy and measurement of collagen and sulfated glycosaminoglycan of
      the acellular tissues. Eight mature rabbits were selected and acellular scaffolds
      were implanted on the exposed urothelium. Urodynamic studies and cystography were
      performed after six months. At 14, 120 and 180days animals were sacrificed and
      augmented bladders were resected. RESULTS: Histological analysis revealed
      formation of muscular layer and blood vessels in implanted scaffolds similar to
      normal bladder. These findings demonstrate the effective seeding of scaffold by
      host bladder cells. The tissue architecture of recellularized scaffold was
      similar to the native bladder. CONCLUSIONS: Fetal intestine acellular matrix
      could be an exceptional scaffold for bladder augmentation cystoplasty and may
      pave the road for future studies in order to be used for clinical application.

PMID- 29459045
TI  - Factors associated with ultrasound-guided water enema reduction for pediatric
      intussusception in resource-limited setting: potential predictive role of
      thrombocytosis and anemia.
AB  - BACKGROUND/PURPOSE: Although ultrasound-guided hydrostatic reduction (USGHR) is
      increasingly used in managing pediatric intussusception, there is limited
      literature concerning its use in Malaysia. We aim to examine the experience and
      factors associated with the effectiveness of USGHR using water. METHODS: This is
      a single-center retrospective observational study in a Malaysian tertiary
      referral center. Children with intussusception admitted between year 2012 and
      2016 were included and medical records reviewed. Factors associated with success
      or failure of USGHR were identified using multivariable logistic regression.
      RESULTS: Of the 172 cases included, 151 cases (87.8%) underwent USGHR, of whom
      129 cases were successfully reduced (success rate of 85.4%). One perforation
      (0.7%) was reported. Age more than 3years old (aOR=7.16; 95% CI=1.07-47.94;
      p=0.042), anemia (aOR=10.12; 95% CI=1.12-91.35; p=0.039), thrombocytosis
      (aOR=11.21; 95% CI=2.06-64.33; p=0.005) and ultrasound findings of free fluid
      (aOR=9.39; 95% CI=1.62-54.38; p=0.012) and left-sided intussusception
      (aOR=8.18;95% CI=1.22-54.90, p=0.031) were independently associated with USGHR
      irreducibility. Symptom duration, blood in stool, vomiting and other clinical
      presentations, however, showed no association. CONCLUSIONS: USGHR with water is
      effective in the non-operative management of pediatric intussusception. Prolonged
      symptom duration need not necessarily preclude USGHR. The findings of anemia and
      thrombocytosis as independent predictors of USGHR irreducibility deserve further
      study. TYPE OF STUDY: Treatment study LEVEL OF EVIDENCE: III.

PMID- 29459046
TI  - Comparison of the biochemical and radiological criteria for lumbar disc
      degeneration.
AB  - BACKGROUND: The relationship between radiological degeneration criteria on lumbar
      magnetic resonance imaging (MRI) and both the keratan sulfate (KS) and
      chondroitin sulfate (ChS) levels was examined in disc material taken from
      patients undergoing lumbar disc herniation (LDH) surgery. To examine whether the
      biochemical and radiological degeneration criteria testing the reliability of
      radiological degeneration findings agreed and to evaluate the contribution of the
      KS/ChS ratio to disc form (protruding or extruding). METHODS: This was a
      prospective experimental cohort study. Using enzyme-linked immunosorbent assay,
      KS and ChS levels were measured in the degenerate nucleus pulposus taken from 71
      patients with a diagnosis of LDH who underwent surgery. The degeneration levels
      and disc form (protruding or extruding) were determined according to the
      Pfirrmann five-stage grading system on preoperative T2-weighted lumbar MRIs.
      According to the Pfirrmann system, 28 patients were grade III and 43 were grade
      IV. The relationship between radiological criteria and the KS/ChS ratio was
      statistically evaluated. RESULTS: The KS levels (p=0.046) and the KS/ChS ratio
      (p=0.001) were significantly higher in grade IV patients than in grade III
      patients. However, there was no difference between the KS and ChS levels and the
      KS/ChS ratio when patients were classified as protruding or extruding according
      to their disc structure. Disc structure and biochemical degeneration indicators
      were not correlated. CONCLUSIONS: The KS level and the KS/ChS ratio were high in
      patients with marked radiological degeneration on lumbar MRI, demonstrating the
      sensitivity and reliability of the Pfirrmann five-stage grading system for
      showing radiological degeneration.

PMID- 29459047
TI  - ?

PMID- 29459048
TI  - ?

PMID- 29459049
TI  - Erratum to "Inter-exam agreement and diagnostic performance of the Korean Thyroid
      Imaging Reporting and Data System for thyroid nodule assessment: Real-time versus
      static ultrasonography" [Eur. J. Radiol. 98 (2018) 14-19].

PMID- 29459050
TI  - N-methyl-d-aspartate-type glutamate receptor modulators and related medications
      for the enhancement of auditory system plasticity in schizophrenia.
AB  - Deficits in N-methyl-d-aspartate-type (NMDAR) function contribute to cognitive
      deficits in schizophrenia, particularly dysfunction in neuroplasticity, defined
      as reduced learning during training on exercises that place implicit, increasing
      demands on early sensory (auditory and visual) information processing. Auditory
      mismatch negativity (MMN) can be both a target engagement biomarker for the NMDAR
      and a proxy measure of neurophysiological plasticity. This review covers the
      evidence for using NMDAR modulator and related compounds for enhancement of
      cognition, with a particular focus on early auditory processing/plasticity.
      Compounds covered include glycine site agonists, glycine and system A-type
      transporter inhibitors, d-amino acid oxidase inhibitors, memantine and nicotinic
      alpha-7 acetylcholine receptor agonists. As opposed to daily treatment studies
      focusing on schizophrenia in general, intermittent, non-daily treatment combining
      NMDAR modulators with neuroplasticity-based paradigms, using MMN as target
      engagement biomarkers show promise as treatments to both remediate plasticity
      deficits and overall functional deficits.

PMID- 29459051
TI  - Response to Lex Wunderink's query as to whether the development of
      supersensitivity could explain the greater risk of relapse in individuals with a
      longer duration of treatment with antipsychotic medication.

PMID- 29459052
TI  - Toxoplasmosis, but not borreliosis, is associated with psychiatric disorders and
      symptoms.

PMID- 29459053
TI  - Virulence genes, capsular and plasmid types of multidrug-resistant CTX-M(-2, -8, 
      15) and KPC-2-producing Klebsiella pneumoniae isolates from four major hospitals
      in Brazil.
AB  - We performed a single-month snapshot study of the population diversity of
      multidrug resistant (MDR) Klebsiella pneumoniae isolates producing carbapenemases
      and/or extended-spectrum beta-lactamases from four major hospitals in Brazil.
      Isolates produced diverse ESBL (CTX-M-2, -8, -15, SHV-2), KPC-2 or both (CTX-M-2
      and KPC-2), linked to specific genetic backgrounds and plasmids from a few
      families (IncR, IncFIIk, IncL/M) that were shared among clonal lineages within
      and between hospitals. A high clonal diversity was identified, among isolates
      from the same ST (ST11, ST15, ST101 or ST340). Diverse capsular types (n=13 K
      types) were identified, most of which linked to specific ST (ST11 and K27 or K64,
      ST101 and K17, ST340 and KL151, ST15 and K24 or ST17 and KL112). Isolates shared
      a common set of virulence genes (ureA, fimH, uge, wabG, mrkD, entB) and
      occasionally ybtS (42%) and kfuBC (18%). Our data suggest intra- and inter
      hospital spread of common genetic structures and international MDR K. pneumoniae
      clones.

PMID- 29459055
TI  - Looking Ahead: The Role of Emergency Physicians in the Opioid Epidemic.

PMID- 29459054
TI  - A case of late-onset cytomegalovirus myocarditis in an orthotopic heart
      transplant recipient; case report and review of the literature.
AB  - We describe a male patient who presents 2 years posttransplant with cough and
      dyspnea. A negative pulmonary workup led to an endomyocardial biopsy and the
      diagnosis of cytomegalovirus (CMV) myocarditis. The patient was treated with
      ganciclovir and intravenous immunoglobulin. This illustrates a very late
      presentation of posttransplant CMV myocarditis and the usefulness of myocardial
      biopsy in diagnosis of CMV carditis.

PMID- 29459056
TI  - Is Procalcitonin Useful in the Diagnosis and Treatment of Acute Respiratory
      Infections in the Emergency Department?

PMID- 29459057
TI  - The Evolving Landscape of HIV Screening in the Emergency Department.

PMID- 29459058
TI  - How Older Adults Experience an Emergency Department Visit: Development and
      Validation of Measures.
AB  - STUDY OBJECTIVE: This study aims to develop and validate measures of experiences
      of an emergency department (ED) visit suitable for use by older adults or their
      family members. METHODS: A cohort of patients aged 75 years and older who were
      discharged home was recruited at 4 EDs. At 1 week after the visit, patients or
      family members were interviewed by telephone to assess problems experienced at
      the visit. Twenty-six questions based on 6 domains of care found in the
      literature were developed: 16 questions were administered to all patients; 10
      questions were administered to bed patients only. Scales were developed with
      multiple correspondence analysis. Regression analyses were used to validate the
      scales, using 2 validation criteria: perceived overall quality of care and
      willingness to return to the same ED. RESULTS: Four hundred twelve patients
      completed the 1-week interview, 197 ambulatory and 215 bed patients; family
      members responded for 75 patients. Two scales were developed, assessing personal
      care and communication (8 questions; alpha=.63) and waiting times (2 questions;
      alpha=.79). Both scales were significantly independently associated with
      perceived overall quality of care and willingness to return to the same ED.
      CONCLUSION: Two scales assessing important aspects of ED care experienced by
      older adults are ready for further evaluation in other settings.

PMID- 29459059
TI  - A brief overview of decommissioning and environmental remediation over the last
      20 years.

PMID- 29459060
TI  - Bickerstaff's brainstem encephalitis with overlapping Guillain-Barre syndrome:
      Usefulness of sequential nerve conduction studies.
AB  - Bickerstaff's brainstem encephalitis (BBE) is a rare immune-mediated disorder
      characterized by ophthalmoplegia, ataxia and disturbance of consciousness, which
      may overlap with Guillain-Barre syndrome (GBS) if there is additional limb
      weakness. We report a 7-month-old boy presented with ophthalmoplegia followed by
      a rapidly ascending paralysis of all four limbs and disturbance of consciousness.
      The initial impression was BBE with overlapping GBS. This was supported by
      sequential nerve conduction study (NCS) findings compatible with an acute
      inflammatory demyelinating polyneuropathy (AIDP). He received intravenous pulse
      methylprednisolone, intravenous immunoglobulin and plasmapharesis with complete
      clinical recovery after 6 weeks of illness and improved NCS findings from week
      16. This is the first case of paediatric BBE with overlapping GBS with an AIDP
      subtype of GBS. It expands the clinical spectrum of this condition in children.
      Our case highlights the importance of sequential NCS in paediatric BBE with
      overlapping GBS for accurate electrophysiological diagnosis and prognosis
      particularly if the first NCS findings are not informative.

PMID- 29459061
TI  - Hemiconvulsion-hemiplegia-epilepsy evolving to contralateral hemi-Lennox-Gastaut
      like phenotype.
AB  - BACKGROUND: Hemiconvulsion-hemiplegia-epilepsy (HHE) involves infantile-onset
      acute hemiconvulsive febrile status epilepticus with subsequent unilateral
      cerebral atrophy and hemiparesis. Chronic epilepsy later develops, typically
      involving refractory focal seizures; however, the underlying pathophysiology of
      this epilepsy is not well understood. PATIENT: We present a boy who had a typical
      acute presentation of HHE at 23 months, but an unusual evolution to chronic
      epilepsy in which the initially unaffected hemisphere was significantly abnormal.
      His initial acute presentation was right-sided hemiconvulsive febrile status
      epilepticus, with subsequent left cerebral hemiatrophy and hemiparesis affecting
      the right face, arm and leg. Focal seizures began at 5 years and were refractory
      to medical treatment. At 9 years, video EEG monitoring showed a striking pattern
      of interictal slow spike-wave and paroxysmal fast activity, maximal over the
      right, initially unaffected, hemisphere. He had primarily focal tonic seizures
      involving left-sided stiffening, also appearing to originate from the right
      hemisphere. Following left functional hemispherotomy he became seizure-free and
      parents reported improved cognitive function, attention and quality of life.
      DISCUSSION: This boy had classic features of Lennox-Gastaut syndrome, but
      expressed almost exclusively over the right hemisphere, which was initially
      unaffected in his acute presentation of HHE. His evolution to "hemi-Lennox
      Gastaut-like phenotype" illustrates the importance of monitoring chronic epilepsy
      in patients with HHE; early surgical intervention might prevent pathologic
      recruitment of bilateral secondary networks leading to the refractory seizures
      and cognitive impairment associated with Lennox-Gastaut syndrome.

PMID- 29459063
TI  - Evaluation of in vitro inhibitory potential of type-I interferons and different
      antiviral compounds on rabies virus replication.
AB  - Five different compounds were tested for their in vitro inhibitory effect against
      RABV multiplication in mouse neuroblastoma (N2A) cell line. N2A cells were
      infected with the fixed RABV strain CVS-11 one hour prior to adding antivirals or
      their respective combinations. The infectious titre of RABV as well as the
      quantity of viral RNA was determined in the cell culturing medium after 48 h. All
      five tested compounds (mouse interferon (IFN)-alpha and -beta, ribavirin,
      favipiravir (T-705) and sorafenib) reduced viral replication in a concentration
      dependent manner: IFN-beta and sorafenib both provided 73.71% relative inhibition
      of viral replication in the highest non-cytotoxic concentration, while ribavirin
      caused 48.07%, IFN-alpha caused 44.87% and favipiravir caused 35.25% relative
      inhibition, respectively. When applied in combination, their antiviral activity
      was not synergistic, but a pronounced inhibition was detected when IFN-beta was
      combined with sorafenib, ribavirin, or favipiravir. The highest antiviral effect
      was caused by the combination of IFN-beta and sorafenib (77.19% relative
      inhibition). In other combinations there was an antagonistic effect detected in
      the reduction of viral replication. The results demonstrate that these compounds
      can be promising candidates for a potential combination treatment of rabies,
      noting that some combinations are not favourable in vitro, which makes thorough
      in vivo studies necessary.

PMID- 29459062
TI  - Cost-effectiveness of a potential vaccine candidate for Haemophilus influenzae
      serotype 'a'.
AB  - The preceding decade has witnessed the emergence of severe community-acquired
      acute infections caused by Haemophilus influenzae serotype a (Hia), with alarming
      incidence rates in North America, particularly among indigenous populations. The
      remarkable success of Hib conjugate vaccine over the past 20 years signify the
      development of an Hia vaccine candidate as a prevention measure to reduce the
      incidence of invasive Hia disease. However, quantifications of the long-term
      epidemiologic and economic impacts of vaccination are needed to inform decision
      on investment in Hia vaccine development and immunization programs. We sought to
      evaluate the cost-effectiveness of an Hia vaccine with a similar routine infant
      immunization schedules currently in practice for Hib in Canada. We developed and
      parameterized an agent-based simulation model using age-specific incidence rates
      reported for Nunavut, a Canadian territory with predominantly aboriginal
      populations. Our results, based on statistical analyses of the incremental cost
      effectiveness ratio, show that an Hia conjugate vaccine is highly cost-effective.
      Sustaining an immunization program with vaccine coverages of 77% for primary
      series and 93% for booster dose over a 10-year period reduces the incidence of
      invasive disease by 63.8% on average from 9.97 to 3.61 cases, per 100,000
      population. The overall costs of disease management in year 10 are reduced by
      53.4% from CDN $1.863 million (95% CI: $1.229-$2.519 M) to CDN $0.868 million
      (95% CI: $0.627-$1.120 M). The findings suggest an important role for a conjugate
      vaccine in managing Hia disease as a growing public health threat.

PMID- 29459064
TI  - Comparison of serum bactericidal and antibody titers induced by two Haemophilus
      influenzae type b conjugate vaccines: A phase III randomized double-blind study.
AB  - Haemophilus influenzae type b (Hib) conjugate vaccines have drastically reduced
      disease incidence worldwide. Protection against Hib infection has relied on the
      serum bactericidal activity (SBA) of antibodies to the Hib capsular
      polysaccharide (polyribosylribitol phosphate). However, licensure usually relies
      on measuring induction of antibodies to PRP as a surrogate for SBA. In a phase
      III clinical trial we compared a PRP-conjugate vaccine using the nontoxic
      diphtheria toxin mutant, CRM197, as carrier protein with the licensed tetanus
      toxoid conjugate when administered subcutaneously as a three dose primary series
      in Japanese infants. As an addition to the phase III study, we have now evaluated
      SBA and show PRP-CRM197 induces higher levels of SBA than PRP-T four weeks after
      the primary series, with a statistically significant correlation with anti-PRP
      titers. This data confirms the superior immunogenicity of PRP-CRM197 compared
      with PRP-T assessed as SBA following a three-dose primary series by subcutaneous
      administration. Clinical trial registry: Registered on ClinicalTrials.gov
      (NCT01379846).

PMID- 29459065
TI  - Assesssing an unmet healthcare demand: A survey of immunisation among homecare
      patients and their caregivers.
AB  - Susceptibility of the homecare patient to vaccine preventable infections and
      their complications is high. Hospitalization of this patient group increases
      costs to the healthcare system. Therefore vaccination services are of great
      importance for protecting these patients from complications and hospitalization.
      We aimed to determine vaccination status of the patients receiving home care
      services from a tertiary hospital in Turkey and to reveal their vaccination
      needs. This cross sectional study was carried out in the Division of Home Care
      Services of Diskapi Yildirim Beyazit Training and Research Hospital in Ankara
      Turkey. A questionnaire Comprised of 15 questions were administered through face
      to face with 336 patients and their care givers. The data obtained was analyzed
      with descriptive statistical methods and chi-squared test was used for comparison
      of proportions. A total of 86.3% of the patients and 22.6% of the caregivers were
      older than age 65. Approximately 45% of the patients were receiving home care due
      to primary neurological diagnosis such as Dementia, Parkinson's disease and
      Cerebrovascular Accident. In addition, 78% of the patients had at least 1
      additional diagnosis other than their primary diagnosis. Although immunization
      indications were present among all patients included in the study and at least
      22% of the care providers, only 15.2% of patients and 11.3% of care providers had
      been recommended to receive vaccination. Among those who had been recommended to
      get vaccinated, 74% of patients and 77% of care givers had been administered the
      recommended vaccine. This finding implied that both groups were responsive to the
      advice for vaccination. Moreover, since the patients receiving home care are
      already followed-up by a healthcare team, thus these patients can be vaccinated
      with very little additional logistic support.

PMID- 29459066
TI  - Ecological thresholds of hypoxia and sedimentary H2S in coastal soft-bottom
      habitats: A macroinvertebrate-based assessment.
AB  - Ecological thresholds of dissolved oxygen (DO) and sedimentary hydrogen sulfide
      (H2S) for macrozoobenthos were examined during a 30-month monitoring of two
      stations in a highly eutrophic canal in inner Tokyo Bay, Japan. Bottom DO and H2S
      concentrations fluctuated seasonally, and were significantly correlated with
      water and sediment temperatures. Red tide-derived phytodetritus was a major
      source of sediment organic matters in the canal bottom, and the sediment became
      highly reduced and sulfidic condition in warmer months (sedimentary H2S; up to
      8.5 mM). Dominant opportunistic taxa, including polychaetes and amphipods, were
      eliminated under low DO and high H2S conditions (i.e., population thresholds),
      and devastation of community structure occurred at 2.4-3.3 mg l-1 DO and 1.8-2.7
      mM H2S (i.e., community thresholds). To maintain ecosystem function in
      anthropogenically degraded habitats and ensure colonization by macrozoobenthos
      throughout the year, DO and H2S levels should be maintained below these
      thresholds.

PMID- 29459067
TI  - Parthenosporophytes of the brown alga Ectocarpus siliculosus exhibit sex
      dependent differences in thermotolerance as well as fatty acid and sterol
      composition.
AB  - In the filamentous brown alga Ectocarpus siliculosus, male and female sex is
      expressed during the haploid parthenosporophyte phase of the life cycle. Here, we
      found that male parthenosporophytes displayed thermotolerance whereas female
      specimens displayed severely reduced viability at 25  degrees C and 28  degrees
      C. Profiling of polyunsaturated fatty acids showed that n-3 and n-6 were the
      predominant species in male and female parthenosporophytes, respectively, and
      that the n-3/n-6 fatty acid ratio was not affected by a temperature change. Both
      male and female parthenosporophytes contained the sterols fucosterol,
      cholesterol, and ergosterol, but these were present at higher levels at 10-25 
      degrees C in female specimens than in males. Thus, these fatty acids and sterols
      would be expected to make the membranes more rigid in the female compared to the
      male, which is opposite to the paradigm that increased rigidity confers
      thermotolerance. Our results suggest that the sex-dependent thermotolerance in E.
      siliculosus parthenosporophytes is not explained by the relationship between
      membrane fluidity and differences in fatty acids and sterol compositions.

PMID- 29459068
TI  - Bioaccumulation and effects of titanium dioxide nanoparticles and bulk in the
      clam Ruditapes philippinarum.
AB  - Biochemical and cellular responses to low concentrations of TiO2 nanoparticles
      (nTiO2, 1 and 10 MUg/L) and bulk (bTiO2, 10 MUg/L) were evaluated in gills,
      digestive gland and haemolymph of the clam Ruditapes philippinarum after1, 3 and
      7 days' exposure. At 7 days, titanium content was determined in gills and
      digestive gland. nTiO2 significantly increased antioxidant enzyme activities in
      both tissues, and lipid peroxidation in digestive gland at 10 MUg/L only, and
      affected glutathione S-transferase activity. Slighter variations were observed in
      bTiO2-treated clams. A significant Ti bioaccumulation was detected in both gills
      and digestive gland of 10 MUg nTiO2/L-exposed clams. In haemolymph, nTiO2
      affected total haemocyte count, haemocyte proliferation, haemocyte diameter and
      volume, and induced DNA damage. Overall, this study demonstrated that TiO2 alters
      most of the biomarkers measured in clams, although responses were differently
      modulated depending on tissues and exposure conditions, and indicated that nTiO2
      can be accumulated by bivalves, suggesting a potential risk for filter-feeding
      animals.

PMID- 29459069
TI  - Otorhinolaryngology surgery analysis in Japan and Thailand: Comparing Nihon
      University School of Medicine with Thammasat University Faculty of Medicine.
AB  - BACKGROUND/OBJECTIVE: We compared the surgery data of the department of
      otorhinolaryngology of the university hospitals in Japan and Thailand to make
      each feature and the differences of both otorhinolaryngology surgeries clear.
      There are some medical meetings and congresses between Japan and Thailand, but so
      far it has not reported about the comparison of surgery data. METHODS:
      Retrospectively, we analyzed the surgical statistics of department of
      otorhinolaryngology of Nihon University Itabashi Hospital (Japan) and Thammasat
      University Hospital (Thailand) between 2013 and 2014. RESULTS: In Japan, there
      were many surgeries involving the middle ear and paranasal sinuses whereas in
      Thailand, tracheotomy and tonsillectomy were more frequently performed.
      Statistical analysis of the surgical data revealed specific tendencies in the
      nature of the operations performed at each university. CONCLUSION: This study
      revealed that there are rather differences between two hospitals' surgeries
      features. It was thought that it would be beneficial to both institutions to gain
      a deeper understanding of the areas of expertise of each university in order to
      foster an environment conducive to increasing future international
      collaborations.

PMID- 29459070
TI  - The influence of mechanical vibration on local and central balance control.
AB  - Fall prevention has an indispensable role in enhancing life expectancy and
      quality of life among older adults. The first step to prevent falls is to devise
      reliable methods to identify individuals at high fall risk. The purpose of the
      current study was to assess alterations in local postural muscle and central
      sensory balance control mechanisms due to low-frequency externally applied
      vibration among elders at high fall risk, in comparison with healthy controls, as
      a potential tool for assessing fall risk. Three groups of participants were
      recruited: healthy young (n = 10; age = 23 +/- 2 years), healthy elders (n = 10;
      age = 73 +/- 3 years), and elders at high fall risk (n = 10; age = 84 +/- 9
      years). Eyes-open and eyes-closed upright standing balance performance was
      measured with no vibration, 30 Hz, and 40 Hz vibration of Gastrocnemius muscles.
      When vibratory stimulation was applied, changes in local-control performance
      manifested significant differences among the groups (p < 0.01). On average
      between conditions, we observed 97% and 92% less change among high fall risk
      participants when compared to healthy young and older adults, respectively. On
      the other hand, vibration-induced changes in the central-control performance were
      not significant between groups (p >= 0.19). Results suggest that local-control
      deficits are responsible for balance behavior alterations among elders at high
      fall risk and healthy individuals. This observation may be attributable to
      deterioration of short-latency reflexive loop in elders at high fall risk. On the
      other hand, we could not ascribe the balance alterations to problems related to
      central nervous system performance or long-latency responses.

PMID- 29459071
TI  - Effects of surrounding fluid on motility of hyperactivated bovine sperm.
AB  - Mammalian spermatozoa in organisms with internal fertilization are required to
      swim in the cervical and oviductal mucus, whose rheological properties differ
      substantially from those of water. Moreover, on the way to the oviduct, a change
      in sperm motility called hyperactivation may occur. In the present study, we
      focused on the motion characteristics of hyperactivated bovine sperm and
      investigated the effect of the surrounding fluid on motility. We prepared two
      kinds of polyacrylamide with high-viscosity non-Newtonian fluid properties,
      similar to the actual cervical and oviductal mucus. Using semen from Japanese
      cattle, we evaluated curvilinear velocity (VCL), straight-line velocity (VSL),
      and average path velocity (VAP). Additionally, we estimated linearity (LIN),
      straightness (STR), and wobble (WOB) as sperm motility parameters for several
      surrounding fluids. We successfully induced hyperactivation of bovine sperm in
      high-viscosity non-Newtonian fluid. Hyperactivation resulted in an increase in
      VCL and a decrease in VSL. In the high-viscosity non-Newtonian fluid, the
      hyperactivated sperm moved in a zig-zag pattern with regularity, different from
      the movement observed in a diluted solution. The increase in WOB in the non
      Newtonian fluid suggests that hyperactivated sperm efficiently progress along the
      groove that exists on the oviductal mucus wall. These results improve our
      understanding of the motility of bovine sperm when they undergo hyperactivation
      in the actual cervical and oviductal mucus.

PMID- 29459072
TI  - Stride length determination during overground running using a single foot-mounted
      inertial measurement unit.
AB  - From a research perspective, detailed knowledge about stride length (SL) is
      important for coaches, clinicians and researchers because together with stride
      rate it determines the speed of locomotion. Moreover, individual SL vectors
      represent the integrated output of different biomechanical determinants and as
      such provide valuable insight into the control of running gait. In recent years,
      several studies have tried to estimate SL using body-mounted inertial measurement
      units (IMUs) and have reported promising results. However, many studies have used
      systems based on multiple sensors or have only focused on estimating SL for
      walking. Here we test the concurrent validity of a single foot-mounted, 9-degree
      of freedom IMU to estimate SL for running. We employed a running-specific, Kalman
      filter based zero-velocity update (ZUPT) algorithm to calculate individual SL
      vectors with the IMU and compared the results to SLs that were simultaneously
      recorded by a 6-camera 3D motion capture system. The results showed that the
      analytical procedures were able to successfully identify all strides that were
      recorded by the camera system and that excellent levels of absolute agreement
      (ICC(3,1) = 0.955) existed between the two methods. The findings demonstrate that
      individual SL vectors can be accurately estimated with a single foot-mounted IMU
      when running in a controlled laboratory setting.

PMID- 29459073
TI  - Erythema Annulare Centrifugum in a Patient With Budd-Chiari Syndrome.

PMID- 29459074
TI  - Modified candy-plug device for aneurysmal false lumen occlusion in chronic type B
      aortic dissection.

PMID- 29459075
TI  - Does being overweight reduce accuracy in predicting an acute aortic dissection?

PMID- 29459076
TI  - The variability of the mitral valve anatomy and terminology.

PMID- 29459077
TI  - Reply to "Letter to the Editor concerning the article-ex vivo heart perfusion
      after cardiocirculatory death; a porcine model".

PMID- 29459078
TI  - Biomechanical, Histologic, and Molecular Evaluation of Tendon Healing in a New
      Murine Model of Rotator Cuff Repair.
AB  - PURPOSE: To develop a clinically relevant, robust murine model of rotator cuff
      tendon repair to examine cellular and molecular mechanisms of healing. METHODS:
      Sixty C57BL/6 male mice underwent rotator cuff transection and repair using
      microsurgical techniques. A modified Kessler suturing technique was used prior to
      tendon detachment. Sutures were passed through 2 intersecting bone tunnels that
      were made at the tendon attachment site. Mice were sacrificed at 2 and 4 weeks
      with subsequent biomechanical, histologic, micro-CT, and gene expression
      evaluations. RESULTS: Failure forces in the 2- and 4-week groups were 36% and 75%
      of the intact tendon, respectively. Histologic evaluation revealed complete
      reattachment of the tendon with no observable gap. Healing occurred by formation
      of fibrovascular tissue at the tendon-bone interface, similar to larger animal
      models. Molecular analysis revealed gene expression consistent with gradual
      healing of the reattached tendon over a period of 4 weeks. Comparisons were made
      using 1-way analysis of variance. CONCLUSIONS: This model is distinguished by use
      of microsurgical suturing techniques, which provides a robust, reproducible, and
      economic animal model to study various aspects of rotator cuff pathology.
      CLINICAL RELEVANCE: Improvement of clinical outcomes of rotator cuff pathology
      requires in-depth understanding of the underlying cellular and molecular
      mechanisms of healing. This study presents a robust murine model of supraspinatus
      repair to serve as a standard research tool for basic and translational
      investigations into signaling pathways, gene expression, and the effect of
      biologic augmentation approaches.

PMID- 29459079
TI  - Anti-hypertensive treatment in peripheral artery disease.
AB  - Peripheral artery disease (PAD) affects more than 200 million people worldwide.
      Hypertension has been related to increased risk of PAD. The treatment of elevated
      blood pressure (BP) in these patients is indicated to lower the cardiovascular
      risk with a BP goal of less than 130/80mmHg. Although there is no evidence that
      one class of antihypertensive medication or strategy is superior for BP lowering
      in PAD, the use of renin-angiotensin-system (RAS) inhibitors can be effective to
      reduce the cardiovascular risk. Beta-blockers (BBs) are not contraindicated. In
      the presence of carotid atherosclerosis, calcium-channel blockers (CCBs) and
      angiotensin-converting-enzyme inhibitors are recommended. In fibromuscular
      dysplasia the treatment of choice is percutaneous renal angioplasty. In renal
      artery disease optimal medical therapy includes RAS inhibitors, CCBs, BBs and
      diuretics.

PMID- 29459080
TI  - Total hip arthroplasty following Girdlestone arthroplasty.
AB  - BACKGROUND: Complications associated with re-implantation of total hip
      arthroplasty (THA) after resection arthroplasty for the treatment of primary
      septic hip arthritis or infected THA and bipolar hemiarthroplasty (BHA) are not
      well-documented. Furthermore, no comparison has been made between septic
      arthritis (SA) and infected THA and BHA. We divided subjects into two groups for
      evaluation: a SA group and an infected THA or BHA group. METHODS: Nineteen hips
      in 19 patients (12 in the SA group, 7 in the infected THA or BHA group) with an
      average of 77 months of follow-up from the time of re-implantation THA were
      retrospectively evaluated. RESULTS: The average Japanese Orthopaedic Association
      hip score improved from 50 points (range, 30 to 73 points) preoperatively to 80
      points (range: 64 to 96 points) at the time of the final follow-up (p < 0.01).
      Intra- and postoperative complications occurred in 11 cases, including
      intraoperative fracture in 1 hip, deep infection in 6 hips, dislocation in 7
      hips, and septic loosening of acetabular component in 2 hips. Following re
      implantation, further surgical revision was required in four cases. Two revisions
      were performed for recurrent infection: one patient had recurrent dislocation of
      one hip, and one patient had recurrent infection and dislocation. The number of
      hips with relapsed infection in the infected THA or BHA group (5 hips) was
      significantly higher than that in the SA group (1 hip) (p < 0.05). CONCLUSIONS:
      Re-implantation after septic hip arthritis or infected THA or BHA was an
      effective treatment for improving the activity of daily life, especially the gait
      function. Furthermore, 94.7% of patients were free of infection at the latest
      follow-up. However, the rate of recurrence of infection was 31.6%, and re
      implantation after resection arthroplasty following infected THA or BHA led to a
      lower rate of infection control than that after primary SA.

PMID- 29459081
TI  - Changes in the diagnosis and treatment of soft tissue sarcoma in Japan, 1977
      2016.
AB  - The treatment of soft tissue tumors has maderemarkable progress through
      advancements in diagnostic imaging and analysis ofsurgical materials. Changes in
      the treatment of soft tissue tumors are describedfrom my experience since 1977.
      Prior to the introduction of CT scans, radiography and angiography were the only
      methods for tumor localization. Wholebody CT, echography, and soft tissue
      radiography were introduced around 1980,and significant progress was seen in the
      localization of soft tissue tumors.Although the localization and diagnostic
      characteristics of tumors becameeasier with the introduction of MRI, radiography
      and ultrasound still remainedthe primary diagnostic method for soft tissue
      tumors. Since 1980, preoperative needle biopsy hasbecome a powerful diagnostic
      procedure by combining rapid cytological andpathological diagnosis at the Cancer
      Institute Hospital.The curative wide resection method, based on barrier theory,
      was an index forpreoperative planning. In addition, with the advent of evaluation
      methods forsurgical margins, the curability of wide resections can be discussed
      on acommon platform to open new possibilities in limited resection.
      However,because current evaluation methods for surgical margins were based
      onmacroscopic findings, diagnostic measures for invasive sarcomas are stillneeded
      in future investigations. The development of In Situ Preparation (ISP) isuseful
      for acquiring information that cannot be obtained with preoperativeimages as it
      allows for intraoperative evaluation of margins without the riskof tumor
      contamination, and the surgical technique could be consideredessential for
      limited resection. In most areas, the preservation of affectedlimbs was made
      possible by combining ISP with vascular reconstruction, flaptransplantation,
      joint arthroplasty, bone grafting, among other techniques. Inorder to improve the
      outcome for the treatment of sarcoma, which is a rarecancer, it is essential to
      consolidate facilities.

PMID- 29459082
TI  - Ideal screw positions for multiple screw fixation in femoral neck fractures -
      Study of proximal femur morphology in a Japanese population.
AB  - BACKGROUND: Despite the fact that multiple screw fixation is a common option of
      surgical treatment for femoral neck fractures, there is a paucity of precise
      morphological study of the femoral neck. To identify appropriate positions and
      spacing of hip screws for multiple-screw femoral neck fracture fixation, proximal
      femur morphology in Japanese patients was studied. METHOD: One hundred hips in
      fifty knee arthroplasty candidates were studied. Following full limb CT, defined
      slices were created and anatomical variables measured. RESULT: The average neck
      shaft angle was 126.5 degrees  and the distance from the subcapital line to the
      subchondral bone on a line parallel to the femoral neck axis (FNA) was
      approximately 25 mm at the superior and inferior; borders of the femoral neck.
      The FNA was shown to run anterior to the femoral axis (FA). The cross section of
      the femoral neck forms a reverse right triangle. The height and width of the neck
      medullary canal were equal (approximately 25 mm), with the posterior wall closer
      to the femoral axis than the anterior wall. CONCLUSION: Based on these data, the
      anterior screw positioned just above the calcar femorale, 16 mm proximal and 27
      degrees  anterior to the FA, and the posterior screw positioned 12 mm proximal
      and 5 mm posterior to the FA is recommended. For screws inserted with a fixed
      angle side-plate, <=130 degrees  is recommended.

PMID- 29459083
TI  - Therapeutic outcomes of muscular advancement by an arthroscopic-assisted modified
      Debeyre-Patte procedure for irreparable large and massive rotator cuff tears.
AB  - BACKGROUND: In cases of the large or massive rotator cuff tears, retear rates
      after rotator cuff repairs remain high. We introduced an arthroscopic-assisted
      modified Debeyre-Patte procedure which enables to decrease the tension of torn
      rotator cuff by sliding supraspinatus and infraspinatus laterally keeping fascia
      connection to the rhomboids. PURPOSE: The objective of this study was to examine
      the clinical outcomes and retear rates after an arthroscopic-assisted modified
      Debeyre-Patte procedure for irreparable large and massive rotator cuff tears.
      METHODS: Thirty-three rotator cuff tear patients (34 shoulders) were selected.
      These patients underwent arthroscopic-assisted modified Debeyre-Patte procedures
      and were observed postoperatively for at least 24 months. Magnetic resonance
      imaging (MRI) was used to evaluate the preoperative location of the torn rotator
      cuff stump and fatty infiltration of the muscles composing the rotator cuff, as
      well as the repaired rotator cuffs. Shoulder functional evaluations through the
      use of the Constant and Murley scores and the University of California Los
      Angeles (UCLA) shoulder score were compared before and after surgery, and the
      preoperative global fatty degeneration index (GFDI) was compared between retear
      and healed shoulders. RESULTS: MRI showed that 77% of shoulders were healed and
      23% exhibited retear postoperatively. The mean preoperative GFDI was 1.99 among
      the 26 healed shoulders and 2.54 among the 8 retear shoulders (p < .05). When the
      Goutallier's classification was grade 3 or lower for all 3 cuff muscles for fatty
      infiltration, the retear rate was 14.3%. The mean Constant and Murley scores in
      healed and retear groups respectively improved from 34.7 +/- 15.8, 30.0 +/- 15.1
      points (p = 0.47) preoperatively to 70.8 +/- 8.3, 53.9 +/- 14.0 points (p <
      .001), and UCLA scores in healed and retear groups from 13.8 +/- 3.9, 12.4 +/-
      5.0 points (p = 0.46) preoperatively to 32.8 +/- 2.7, 28.4 +/- 3.6 points (p <
      .001). CONCLUSION: The clinical outcomes of healed shoulders after the
      arthroscopic-assisted modified Debeyre-Patte procedure were favorable. If the
      torn rotator cuff stump is retracted near the glenoid fossa, and the rotator cuff
      muscle scored Goutallier grade 3 or lower, this modified Debeyre-Patte procedure
      would be a viable option.

PMID- 29459085
TI  - Best practice guidelines on management of mild neonatal encephalopathy: Is it
      really mild?

PMID- 29459084
TI  - A screening method to distinguish syndromic from sporadic spinal extradural
      arachnoid cyst.
AB  - BACKGROUND: Spinal extradural arachnoid cyst (SEDAC) is a cystic lesion that
      protrudes into the epidural space from a small dural defect. Early diagnosis of
      SEDAC is important because its expansion causes neurological damage. Two types of
      SEDAC, syndromic and sporadic, are present. Syndromic SEDAC is inherited as a
      part of lymphedema-distichiasis syndrome caused by mutations in the FOXC2 gene;
      however, it is often mistaken as sporadic because of low penetrance. It is not
      reasonable to conduct a genetic testing for all SEDAC patients and their family
      members. The aim of this study is to establish an effective screening method to
      distinguish syndromic SEDAC from sporadic SEDAC. METHODS: We performed a
      retrospective review of medical records and imaging studies of 29 subjects who
      were diagnosed with SEDAC. Clinical features, family history and magnetic
      resonance imaging (MRI) were analyzed. Mutations in FOXC2 were examined by Sanger
      sequencing of the entire coding region of the genes. SEDAC having a mutation in
      FOXC2 gene was defined with syndromic SEDAC. RESULTS: Eleven subjects had a
      heterozygous mutation in FOXC2. They were all familial and hence syndromic SEDAC.
      Only one proband had known family history of SEDAC at diagnosis. MRI findings and
      physical examinations, especially eye and leg examinations, were quite useful to
      screen syndromic SEDAC. Physical examination often showed accompanying lymphedema
      and distichiasis in syndromic SEDAC. Syndromic SEDAC tended to have multiple
      cysts out of the thoracolumbar area. CONCLUSIONS: We established an effective
      screening method based on physical examinations and MRI findings.

PMID- 29459086
TI  - Comparative study of strong cation exchangers: Structure-related chromatographic
      performances.
AB  - Chromatographic performances are highly influenced by operational parameters. New
      ion exchangers have tailored matrices providing low backpressure, thereby
      allowing high flow velocity. By systematic frontal analysis and selectivity
      determination at different flow rates, we independently evaluated cation
      exchangers to facilitate media selection and investigated the relationship
      between surface modification and chromatographic performances. Structure-extended
      resins showed higher binding capacities compared to resins with conventional
      ligands directly attached to the matrix. Moreover, they maintained high
      capacities even with high flow velocities. Ligand accessibility was therefore
      largely enhanced, allowing proteins to interact and bind under harsh conditions
      with minimal residence/contact time. High throughput resins can be used for
      purification of high volume and high concentration feedstock in limited time.
      This results in higher productivity, and could contribute to cost reduction. In
      this work, we evaluated the dynamic binding capacities of various new ion
      exchange resins at different binding conductivities for different residence
      times, and observed that.

PMID- 29459087
TI  - Identification of five Mitragyna alkaloids in urine using liquid chromatography
      quadrupole/time of flight mass spectrometry.
AB  - Mitragyna speciosa (Kratom) is a psychoactive plant that has recently emerged as
      a recreational drug. Mitragyna alkaloids are not within the scope of traditional
      forensic toxicology screening methods, which may contribute to under-reporting.
      Solid phase extraction (SPE) and liquid chromatography-quadrupole/time of flight
      mass spectrometry (LC-Q/TOF-MS) were used to identify five alkaloids in urine.
      Target analytes included the two known psychoactive compounds, mitragynine and 7
      hydroxymitragynine, in addition to speciociliatine, speciogynine, and
      paynantheine. Two deuterated internal standards (mitragynine-D3 and 7
      hydroxymitragynine-D3) were employed. Using traditional reversed phase
      chromatography all compounds and isomers were separated in 10 min. The procedure
      was validated in accordance with the Scientific Working Group for Forensic
      Toxicology (SWGTOX) Standard Practices for Method Validation. Extraction
      efficiencies were 63-96% and limits of quantitation were 0.5-1 ng/mL. Precision,
      bias and matrix effects were all within acceptable thresholds, with the exception
      of 7-hydroxymitragynine, which is notably unstable and unsuitable for
      quantitative analysis. In this paper we present a simultaneous quantitative
      analytical method for mitragynine, speciociliatine, speciogynine and
      paynantheine, and a qualitative assay for 7-hydroxymitragynine in urine using
      high resolution mass spectrometry (HRMS).

PMID- 29459088
TI  - Purification of antibody fragments for the reduction of charge variants using
      cation exchange chromatography.
AB  - Recently, antibody fragments have been studied as therapeutic agents because they
      lack Fc effector function while having affinity similar to their original
      monoclonal antibody and can be produced using E. coli. Antibody fragments can be
      purified using affinity chromatography in the capture step, although they need a
      polishing step because of product-related impurities, mainly charge variants.
      Unlike monoclonal antibodies, few studies exist regarding the separation of
      charge variants in antibody variants. In this study, an efficient separation of
      charge variant method was assessed using a cation exchange chromatography resin
      with salt and a pH gradient. The SP ImpRes resin and pH gradient exhibited the
      most effective separation potency using combinations of resin and the separation
      method. The antibody fragment that did not undergo the charge variant separation
      process exhibited a difference in the tertiary structure of the protein and in
      vivo pharmacokinetics. However, the antibody fragment was similar to the
      reference protein when the charge variant separation process was performed. These
      results are expected to support efficient charge variant separation of antibody
      fragments and to be applied to the industrial production of therapeutic antibody
      fragments.

PMID- 29459089
TI  - The Role of Quantum Decoherence in FRET.
AB  - Resonance energy transfer has become an indispensable experimental tool for
      single-molecule and single-cell biophysics. Its physical underpinnings, however,
      are subtle: it involves a discrete jump of excitation from one molecule to
      another, and so we regard it as a strongly quantum-mechanical process. And yet
      its kinetics differ from what many of us were taught about two-state quantum
      systems, quantum superpositions of the states do not seem to arise, and so on.
      Although J. R. Oppenheimer and T. Forster navigated these subtleties
      successfully, it remains hard to find an elementary derivation in modern
      language. The key step involves acknowledging quantum decoherence. Appreciating
      that aspect can be helpful when we attempt to extend our understanding to
      situations in which Forster's original analysis is not applicable.

PMID- 29459090
TI  - [Thyroid carcinoma on struma ovarii: Diagnosis and treatment].
AB  - Thyroid carcinoma on struma ovarii (TCSO) is a rare ovarian tumour, derivate from
      monodermic teratomas. It represents about 0.01% of overall ovarian tumours and 5
      to 10% of struma ovarii. The diagnosis is histologic and retrospective after
      pelvic surgery; radiographic imaging being unspecific. Because of its rarity, the
      treatment of TCSO is not consensual and should be validated in multidisciplinary
      team involved in rare ovarian carcinoma. The first treatment is a surgical
      removal, with a laparoscopic approach. A fertility-conservative surgery is
      recommended for young women. If the tumour is unresectable and/or with metastatic
      spread, an adjuvant iodine 131 treatment might be proposed after thyroidectomy.
      Recurrence of TCSO should be taken care of as a thyroid carcinoma with tyrosine
      kinase inhibitor in case of progressive distant relapse, refractory to iodine 131
      treatment. If the recurrence is localised, a complete surgery is the preferred
      option. There is no gold standard for the follow up.

PMID- 29459091
TI  - Erratum to "Evolution of hepatocellular carcinoma epidemiology in Cote d'Ivoire"
      [Bull. Cancer 104 (2017) 937-945].

PMID- 29459092
TI  - Revision of the International Society of Nephrology/Renal Pathology Society
      classification for lupus nephritis: clarification of definitions, and modified
      National Institutes of Health activity and chronicity indices.
AB  - We present a consensus report pertaining to the improved clarity of definitions
      and classification of glomerular lesions in lupus nephritis that derived from a
      meeting of 18 members of an international nephropathology working group in
      Leiden, Netherlands, in 2016. Here we report detailed recommendations on issues
      for which we can propose adjustments based on existing evidence and current
      consensus opinion (phase 1). New definitions are provided for mesangial
      hypercellularity and for cellular, fibrocellular, and fibrous crescents. The term
      "endocapillary proliferation" is eliminated and the definition of endocapillary
      hypercellularity considered in some detail. We also eliminate the class IV-S and
      IV-G subdivisions of class IV lupus nephritis. The active and chronic
      designations for class III/IV lesions are replaced by a proposal for activity and
      chronicity indices that should be applied to all classes. In the activity index,
      we include fibrinoid necrosis as a specific descriptor. We also make
      recommendations on issues for which there are limited data at present and that
      can best be addressed in future studies (phase 2). We propose to proceed to these
      investigations, with clinicopathologic studies and tests of interobserver
      reproducibility to evaluate the applications of the proposed definitions and to
      classify lupus nephritis lesions.

PMID- 29459093
TI  - Sox11 gene disruption causes congenital anomalies of the kidney and urinary tract
      (CAKUT).
AB  - Congenital abnormalities of the kidney and the urinary tract (CAKUT) belong to
      the most common birth defects in human, but the molecular basis for the majority
      of CAKUT patients remains unknown. Here we show that the transcription factor
      SOX11 is a crucial regulator of kidney development. SOX11 is expressed in both
      mesenchymal and epithelial components of the early kidney anlagen. Deletion of
      Sox11 in mice causes an extension of the domain expressing Gdnf within rostral
      regions of the nephrogenic cord and results in duplex kidney formation. On the
      molecular level SOX11 directly binds and regulates a locus control region of the
      protocadherin B cluster. At later stages of kidney development, SOX11 becomes
      restricted to the intermediate segment of the developing nephron where it is
      required for the elongation of Henle's loop. Finally, mutation analysis in a
      cohort of patients suffering from CAKUT identified a series of rare SOX11
      variants, one of which interferes with the transactivation capacity of the SOX11
      protein. Taken together these data demonstrate a key role for SOX11 in normal
      kidney development and may suggest that variants in this gene predispose to CAKUT
      in humans.

PMID- 29459094
TI  - Training pharmacy technicians to administer immunizations.
AB  - OBJECTIVES: To evaluate the effectiveness of an immunization training program for
      pharmacy technicians on technicians' self-reported confidence, knowledge, and
      number of vaccines administered. METHODS: A one-group pre- and posttest study was
      conducted with certified pharmacy technicians from Albertsons and Safeway
      community pharmacies in Idaho. Thirty pharmacy technicians were recruited to
      participate in an immunization administration training program comprising a 2
      hour home study and a 2-hour live training. Pharmacy technician scores on a 10
      question knowledge assessment, responses on a pre- and posttraining survey, and
      number of immunizations administered in the 6-month period following the training
      were collected. RESULTS: Twenty-five pharmacy technicians completed the home
      study and live portions of the immunization training program. All 29 pharmacy
      technicians who took the home study assessment passed with greater than 70%
      competency on the first attempt. Technicians self-reported increased confidence
      with immunization skills between the pretraining survey and the posttraining
      survey. From December 2016 to May 2017, the technicians administered 953
      immunizations with 0 adverse events reported. CONCLUSION: For the first time,
      pharmacy technicians have legally administered immunizations in the United
      States. Trained pharmacy technicians demonstrated knowledge of vaccination
      procedures and self-reported improved confidence in immunization skills and
      administered immunizations after participating in a 4-hour training program.

PMID- 29459095
TI  - The pharmacist's role in supporting people living with cystic fibrosis.
AB  - OBJECTIVES: To describe the critical need for pharmacists' involvement in
      outpatient care for people living with cystic fibrosis (CF). DATA SOURCES: Not
      applicable. SUMMARY: CF is a pulmonary condition that affects more than 30,000
      children and adults in the United States and 70,000 people worldwide. Various
      complex medication regimens are given to patients with CF, some depending on the
      type of mutation they have in their CF transmembrane conductance regulator
      protein. With complex medication regimens and the increased number and variety of
      treatments that have become available, the medication use burden intensifies for
      individuals living with CF and their caregivers. Young people living with CF have
      a particularly difficult time adhering to medications and other therapies as they
      begin to rely less on their caregivers and assume greater medication management
      responsibility for their care. Adolescents report low adherence rates from about
      40% to 47% for airway clearance methods and even lower for nutritional
      recommendations, about 16% to 20%. In inpatient settings, pharmacists have been
      successful in making medication use recommendations that have improved adherence
      for patients with CF while in the hospital. However, limited research has
      explored how provision of pharmacist supportive care and patient education in
      outpatient settings can improve medication adherence and quality of life for
      people living with CF. CONCLUSION: There is potential for provision of outpatient
      pharmacy clinical services to increase medication adherence and overall quality
      of care for patients with CF. Higher rates of medication adherence in patients
      with CF could in turn improve patient outcomes and reduce overall health care
      costs as a result of fewer rehospitalizations. Pharmacies can implement programs
      designed to provide comprehensive support services and medication management from
      pharmacists and staff that are trained in CF care.

PMID- 29459096
TI  - Objective structured clinical examination "Death Certificate" station - Computer
      based versus conventional exam format.
AB  - One option for improving the quality of medical post mortem examinations is
      through intensified training of medical students, especially in countries where
      such a requirement exists regardless of the area of specialisation. For this
      reason, new teaching and learning methods on this topic have recently been
      introduced. These new approaches include e-learning modules or SkillsLab
      stations; one way to objectify the resultant learning outcomes is by means of the
      OSCE process. However, despite offering several advantages, this examination
      format also requires considerable resources, in particular in regards to medical
      examiners. For this reason, many clinical disciplines have already implemented
      computer-based OSCE examination formats. This study investigates whether the
      conventional exam format for the OSCE forensic "Death Certificate" station could
      be replaced with a computer-based approach in future. For this study, 123
      students completed the OSCE "Death Certificate" station, using both a computer
      based and conventional format, half starting with the Computer the other starting
      with the conventional approach in their OSCE rotation. Assignment of examination
      cases was random. The examination results for the two stations were compared and
      both overall results and the individual items of the exam checklist were analysed
      by means of inferential statistics. Following statistical analysis of examination
      cases of varying difficulty levels and correction of the repeated measures
      effect, the results of both examination formats appear to be comparable. Thus, in
      the descriptive item analysis, while there were some significant differences
      between the computer-based and conventional OSCE stations, these differences were
      not reflected in the overall results after a correction factor was applied (e.g.
      point deductions for assistance from the medical examiner was possible only at
      the conventional station). Thus, we demonstrate that the computer-based OSCE
      "Death Certificate" station is a cost-efficient and standardised format for
      examination that yields results comparable to those from a conventional format
      exam. Moreover, the examination results also indicate the need to optimize both
      the test itself (adjusting the degree of difficulty of the case vignettes) and
      the corresponding instructional and learning methods (including, for example, the
      use of computer programmes to complete the death certificate in small group
      formats in the SkillsLab).

PMID- 29459097
TI  - Evaluation of the relationship between mandibular condyle cortication and
      chronologic age with cone beam computed tomography.
AB  - PURPOSE: The aim of the present study is to evaluate the relationship between
      mandibular condyle cortication and chronologic age and gender via cone-beam
      computed tomography (CBCT) and to investigate the effectiveness of using the
      condylar cortication as a new method of age estimation. METHODS: CBCT images from
      433 subjects aged 8 to 31 years were included in this study. The right and left
      condyle cortication were assessed on the sagittal plane separately for each
      individual by the same investigator via a new method that describes the
      cortication of the condyle. Type I: There is no cortication on the condyle. Type
      II: The bone that is on the superior surface of the condyle is seen less density
      than the structures around the condyle. Type III: The surface of the condyle is
      seen similar or higher density than the surrounding cortical areas. RESULTS: The
      type of the condyle cortication in the right and left mandible was similar for
      almost each subject and there was no statistically significant different between
      them (p = 0.375). When we evaluated the results without including these patients
      for male, Type I cortication of the condyle was seen at 14.14 +/- 2.3 years, Type
      II cortication of the condyle was seen at 16.11 +/- 3.18 years and Type III
      cortication of the condyle was seen at 19.39 +/- 3.96 years. For the female, Type
      I cortication of the condyle was seen at 13.01 +/- 2.16 years, Type II
      cortication of the condyle was seen at 15.52 +/- 2.71 years and Type III
      cortication of the condyle was seen at 17.95 +/- 3.13 years. The minimum age of
      Type III cortication was 11 and 15 years old for male and female, respectively.
      However, there are subjects, who are 30 year old man and 31 year old female, have
      no cortication as much as similar or higher than the surrounding the cortical
      areas. CONCLUSION: This study is the first investigation of the relationship
      between condyle cortication and chronologic age with CBCT in the Turkish
      population. The type of cortication in the right and left condyle may be
      different for the same individual. Chronologic age increased as the stages of the
      cortication process from Type I to Type III in male and female individuals, and
      all the stages of the cortication in the mandibular condyle of male occur later
      time according to female.

PMID- 29459098
TI  - Preparing for Proton Therapy.

PMID- 29459099
TI  - Proton Therapy for Craniopharyngioma - An Early Report from a Single European
      Centre.
AB  - AIMS: Proton beam therapy (PBT) is being increasingly used for craniopharyngioma.
      We describe our early outcome of patients treated with PBT. MATERIALS AND
      METHODS: Between August 2013 and July 2016, 18 patients with craniopharyngiomas
      were treated with 54 Cobalt Gray Equivalent (CGE) in 30 fractions over 6 weeks at
      our centre. The early outcome of 16 patients included in a registry study was
      analysed. Radiological response was assessed by RECIST criteria and the disease-
      and treatment-related toxicities were scored according to the CTCAE 4.0. RESULTS:
      All patients are alive at a median follow-up of 32.6 months (range 9.2-70.6
      months) from initial diagnosis. The median age at PBT was 10.2 years (range 5.4
      46.9 years). One patient progressed 8.7 months after PBT and subsequently had
      complete resection of the tumour. At a median follow-up of 18.4 months after PBT,
      five patients remained in complete remission, four in partial remission and seven
      with stable disease. The most common adverse effects during PBT were grade 1
      (cutaneous in seven patients and fatigue in six patients). There were no
      treatment-related grade 3 toxicities. CONCLUSIONS: Our early results are
      encouraging and comparable with the limited literature on PBT for
      craniopharyngioma.

PMID- 29459100
TI  - Patient Involvement in the Design of a Phase III Trial Comparing Intensity
      modulated Proton Therapy and Intensity-modulated Radiotherapy for Oropharyngeal
      Cancer.

PMID- 29459101
TI  - EXTREQOL Identifies Ongoing Challenges in Maximising Quality of Survival in Men
      with Metastatic Castrate-resistant Prostate Cancer.

PMID- 29459103
TI  - An explanation for under-estimation of high mobile phone use.

PMID- 29459102
TI  - Older Age, Early Symptoms and Physical Function are Associated with the Severity
      of Late Symptom Clusters for Men Undergoing Radiotherapy for Prostate Cancer.
AB  - AIMS: To identify symptom clusters and predisposing factors associated with long
      term symptoms and health-related quality of life after radiotherapy in men with
      prostate cancer. MATERIALS AND METHODS: Patient-reported outcomes (PROs) data
      from the Medical Research Council RT01 radiotherapy with neoadjuvant androgen
      deprivation therapy trial of 843 patients were used. PROs were collected over 5
      years with the University of California, Los Angeles Prostate Cancer Index (UCLA
      PCI) and the 36 item Short-Form Health Survey (SF-36). Symptom clusters were
      explored using hierarchical cluster analysis. The association of treatment dose,
      baseline patient characteristics and early symptom clusters with the change in
      severity of PROs over 3 years was investigated with multivariate linear mixed
      effects models. RESULTS: Seven symptom clusters of three or more symptoms were
      identified. The clusters were stable over time. The longitudinal profiles of
      symptom clusters showed the onset of acute symptoms during treatment for all
      symptom clusters and significant recovery by 6 months. Some clusters, such as
      physical health and sexual function, were adversely affected more than others by
      androgen deprivation therapy, and were less likely to return to pretreatment
      levels over time. Older age was significantly associated with decreased long-term
      physical function, physical health and sexual function (P < 0.001). Both baseline
      and acute symptom clusters were significant antecedents for impaired function and
      health-related quality of life at 3 years. CONCLUSIONS: Men with poorer physical
      function and health before or during treatment were more likely to report poorer
      PROs at year 3. Early assessment using PROs and lifestyle interventions should be
      used to identify those with higher needs and provide targeted rehabilitation and
      symptom management.

PMID- 29459104
TI  - Use of microalgae to recycle nutrients in aqueous phase derived from hydrothermal
      liquefaction process.
AB  - Hydrothermal liquefaction (HTL) of microalgae biomass generates an aqueous phase
      (AP) byproduct with limited energy value. Recycling the AP solution as a source
      of nutrients for microalgae cultivation provides an opportunity for a cost
      effective production of HTL based biofuel and algal biomass feedstock for HTL,
      allowing a closed-loop biofuel production in microalgae HTL biofuel system. This
      paper aims to provide a comprehensive overview of characteristics of AP and its
      nutrients recycling for algae production. Inhibitory effects resulted from the
      toxic compounds in AP and alleviation strategies are discussed.

PMID- 29459105
TI  - Sequestration and utilization of carbon dioxide by chemical and biological
      methods for biofuels and biomaterials by chemoautotrophs: Opportunities and
      challenges.
AB  - To meet the CO2 emission reduction targets, carbon dioxide capture and
      utilization (CCU) comes as an evolve technology. CCU concept is turning into a
      feedstock and technologies have been developed for transformation of CO2 into
      useful organic products. At industrial scale, utilization of CO2 as raw material
      is not much significant as compare to its abundance. Mechanisms in nature have
      evolved for carbon concentration, fixation and utilization. Assimilation and
      subsequent conversion of CO2 into complex molecules are performed by the
      photosynthetic and chemolithotrophic organisms. In the last three decades,
      substantial research is carry out to discover chemical and biological conversion
      of CO2 in various synthetic and biological materials, such as carboxylic acids,
      esters, lactones, polymer biodiesel, bio-plastics, bio-alcohols,
      exopolysaccharides. This review presents an over view of catalytic transformation
      of CO2 into biofuels and biomaterials by chemical and biological methods.

PMID- 29459106
TI  - Building Sangha in the American Healthcare Setting for Persons with Chronic
      Disease.
AB  - BACKGROUND: For persons with chronic disease, participation in meditation
      interventions can reduce anxiety, depression, and chronic disease symptoms in a
      dose dependent fashion. Unfortunately, information about how to support long-term
      participation in such an intervention is lacking. Therefore, a recent discovery
      of persons with chronic lung disease who have maintained a self-led meditation
      group for more than four years created an opportunity to analyze experiences,
      meanings and relationship dynamics of this community-based meditation group.
      METHODS: A focused ethnography was conducted using the following techniques:
      participant observation of four group meditation sessions, semi-structured
      interviews of six group participants, the interviewer's reflective practice and
      collection of demographic information. Analysis of transcribed audio-recordings
      followed an iterative approach. RESULTS: Findings highlighted the inclusive
      nature of the group sessions that supported meditation practice through the
      processing of ancient wisdom traditions similar to a traditional Sangha.
      Reflecting the current culture of non-affiliation, the group often moved beyond
      religious teachings to use the environment, literature and pop culture
      representations to teach wisdom traditions. Data analysis revealed that the
      holistic group characteristics of wisdom circling, non-Stopping, organic way
      finding and sacred space were supported by identifiable yet inseparable
      individual and group actions. This holistic pattern is best described through the
      metaphor of flocking birds. CONCLUSIONS: This self-led group supports long term
      meditation practice and provides a sense of eudemonic well-being for a diverse
      group of individuals in an accessible community setting.

PMID- 29459107
TI  - Analysis of economic and social costs of adverse events associated with blood
      transfusions in Spain.
AB  - OBJECTIVE: To calculate, for the first time, the direct and social costs of
      transfusion-related adverse events in order to include them in the National
      Healthcare System's budget, calculation and studies. In Spain more than 1,500
      patients yearly are diagnosed with such adverse events. METHOD: Blood transfusion
      related adverse events recorded yearly in Spanish haemovigilance reports were
      studied retrospectively (2010-2015). The adverse events were coded according to
      the classification of Diagnosis-Related Groups. The direct healthcare costs were
      obtained from public information sources. The productivity loss (social cost)
      associated with adverse events was calculated using the human capital and hedonic
      salary methodologies. RESULTS: In 2015, 1,588 patients had adverse events that
      resulted in direct health care costs (4,568,914?) and social costs due to
      hospitalization (200,724?). Three adverse reactions resulted in patient death (at
      a social cost of 1,364,805?). In total, the cost of blood transfusion-related
      adverse events was 6,134,443? in Spain. For the period 2010-2015: the trends show
      a reduction in the total amount of transfusions (2 vs. 1.91M?; -4.4%). The number
      of adverse events increased (822 vs. 1,588; +93%), as well as their related
      direct healthcare cost (3.22 vs. 4.57M?; +42%) and the social cost of
      hospitalization (110 vs 200M?; +83%). Mortality costs decreased (2.65 vs. 1.36M?;
      -48%). DISCUSSION: This is the first time that the costs of post-transfusion
      adverse events have been calculated in Spain. These new figures and trends should
      be taken into consideration in any cost-effectiveness study or trial of new
      surgical techniques or sanitary policies that influence blood transfusion
      activities.

PMID- 29459108
TI  - Aortic Migration of a Septal Occluder.

PMID- 29459109
TI  - Endograft Relining Plus Adjunctive Endoanchors for Disconnection and Migration in
      Aortic Arch Pseudoaneurysm Hybrid Treatment.

PMID- 29459110
TI  - A Case of Multiple Ventricular Gradients.

PMID- 29459111
TI  - A Trial of Two Anesthetic Regimes for Minimally Invasive Mitral Valve Repair.
AB  - OBJECTIVE: Minimally invasive mitral valve repair may be associated with
      prolonged cardioplegic arrest times and ischemic reperfusion injury. Intravenous
      (propofol) and volatile (sevoflurane) anesthesia are used routinely during
      cardiac surgery and are thought to provide cardioprotection; however, the
      individual contribution of each regimen to cardioprotection is unknown.
      Therefore, the authors sought to compare the cardioprotective effects of propofol
      and sevoflurane anesthesia in patients undergoing minimally invasive mitral valve
      repair. DESIGN: A single-center single-blind randomized controlled trial.
      SETTING: A specialized regional cardiac surgery center in Italy. PARTICIPANTS:
      The study enrolled 62 adults undergoing elective isolated minimally invasive
      mitral valve repair for degenerative disease. Exclusion criteria included
      secondary mitral regurgitation, previously treated coronary artery disease,
      diabetes mellitus, chronic renal failure requiring dialysis, atrial fibrillation,
      and documented allergy to either propofol or sevoflurane. INTERVENTIONS: All
      patients received video-assisted minimally invasive right minithoracotomy.
      Patients were randomized to receive propofol or sevoflurane anesthesia in a 1:1
      ratio. MEASUREMENTS AND MAIN RESULTS: Cardiac troponin I release was measured
      over the first 72 hours postoperatively. Operative, cross-clamp, and total bypass
      times were similar between groups. Cardiac troponin I release was reduced
      nonsignificantly in the propofol group (p = 0.62), and peak troponin I release
      was correlated with cross-clamp time in both groups. There were no differences in
      terms of intraoperative lactate release and blood pH between groups. CONCLUSION:
      Propofol and sevoflurane anesthesia were associated with similar degrees of
      myocardial injury, indicating comparable cardioprotection. Myocardial injury was
      related directly to the duration of cardioplegic arrest.

PMID- 29459112
TI  - How to Measure Tissue Oxygenation Using Near-Infrared Spectroscopy in a Patient
      With Alkaptonuria.

PMID- 29459113
TI  - Sickle-cell trait and diagnosis of type 2 diabetes.

PMID- 29459114
TI  - High dietary glycemic load was associated with the presence and burden of
      cerebral small vessel diseases in acute ischemic stroke patients.
AB  - Cerebral small vessel diseases (SVDs) are closely associated with stroke.
      Elevated postprandial blood glucose is also an important risk factor for stroke.
      Dietary glycemic load (GL) and glycemic index (GI) are frequently used as markers
      of postprandial blood glucose response used as an estimator of the overall
      glycemic effect of the diet. We hypothesized that high dietary GL or GI will be
      associated with presence of cerebral SVDs in patients with acute ischemic stroke.
      We prospectively included 263 patients who had experienced first-ever symptomatic
      cerebral infarction within 7 days after symptom onset and who submitted a fully
      filled-in semi-quantitative food frequency questionnaire. The dietary GL and GI
      values of food were constructed through an International table based on glucose.
      The presence and burden of high-grade white matter hyperintensities (HWMHs),
      cerebral microbleeds (CMBs), high-grade perivascular spaces (HPVSs) and
      asymptomatic lacunar infarctions (ALIs) were investigated. Mean age of the total
      patient population was 65.4 +/- 11.7 years. After adjusting for age, sex, and
      variables with P < .1 in univariate analysis, high dietary GL was independently
      associated with an increased risk of presence of HWMHs (odds ratio (OR) (95%
      confidence interval (CI)) comparing the top quartile with the bottom quartile:
      3.31 (1.37-7.98); P (for trend) = .006), CMBs (OR (95% CI): 3.06 (1.06-8.85); P =
      .032), PVSs (OR (95% CI): 3.24 (0.75-13.90); P = .039), and ALIs (OR (95% CI):
      2.44 (0.97-6.13); P = .037). In conclusion, high dietary GL was associated with
      the presence and burden of cerebral SVDs in patients with acute cerebral
      infarction.

PMID- 29459115
TI  - Inflammatory bowel disease and risk of Parkinson's disease in Medicare
      beneficiaries.
AB  - INTRODUCTION: Gastrointestinal (GI) dysfunction precedes the motor symptoms of
      Parkinson's disease (PD) by several years. PD patients have abnormal aggregation
      of intestinal alpha-synuclein, the accumulation of which may be promoted by
      inflammation. The relationship between intestinal alpha-synuclein aggregates and
      central nervous system neuropathology is unknown. Recently, we observed a
      possible inverse association between inflammatory bowel disease (IBD) and PD as
      part of a predictive model of PD. Therefore, the objective of this study was to
      examine the relationship between PD risk and IBD and IBD-associated conditions
      and treatment. METHODS: Using a case-control design, we identified 89,790 newly
      diagnosed PD cases and 118,095 population-based controls >65 years of age using
      comprehensive Medicare data from 2004-2009 including detailed claims data. We
      classified IBD using International Classification of Diseases version 9 (ICD-9)
      diagnosis codes. We used logistic regression to calculate odds ratios (ORs) and
      95% confidence intervals (CIs) to evaluate the association between PD and IBD.
      Covariates included age, sex, race/ethnicity, smoking, Elixhauser comorbidities,
      and health care use. RESULTS: PD was inversely associated with IBD overall (OR =
      0.85, 95% CI 0.80-0.91) and with both Crohn's disease (OR = 0.83, 95% CI 0.74
      0.93) and ulcerative colitis (OR = 0.88, 95% CI 0.82-0.96). Among beneficiaries
      with >=2 ICD-9 codes for IBD, there was an inverse dose-response association
      between number of IBD ICD-9 codes, as a potential proxy for IBD severity, and PD
      (p-for-trend = 0.006). CONCLUSION: IBD is associated with a lower risk of
      developing PD.

PMID- 29459116
TI  - Can aquatic macrophytes be biofilters for gadolinium based contrasting agents?
AB  - The use of gadolinium-based contrasting agents (GBCA) is increasing because of
      the intensive usage of these agents in magnetic resonance imaging (MRI). Waste
      water treatment does not reduce anthropogenic Gd-concentration significantly.
      Anomalous Gd-concentration in surface waters have been reported worldwide.
      However, removal of GBCA-s by aquatic macrophytes has still hardly been
      investigated. Four aquatic plant species (Lemna gibba, Ceratophyllum demersum,
      Elodea nuttallii, E. canadensis) were investigated as potential biological
      filters for removal of commonly used but structurally different GBCA-s (Omniscan,
      Dotarem) from water. These plant species are known to accumulate heavy metals and
      are used for removing pollutants in constructed wetlands. The Gd uptake and
      release of the plants was examined under laboratory conditions. Concentration
      dependent infiltration of Gd into the body of the macrophytes was measured,
      however significant bioaccumulation was not observed. The tissue concentration of
      Gd reached its maximum value between day one and four in L. gibba and C.
      demersum, respectively, and its volume was significantly higher in C. demersum
      than in L. gibba. In C. demersum, the open-chain ligand Omniscan causes two-times
      higher tissue Gd concentration than the macrocyclic ligand Dotarem. Gadolinium
      was released from Gd-treated duckweeds into the water as they were grown further
      in Gd-free nutrient solution. Tissue Gd concentration dropped by 50% in duckweed
      treated by Omniscan and by Dotarem within 1.9 and 2.9 days respectively. None of
      the macrophytes had a significant impact on the Gd concentration of water in low
      and medium concentration levels (1-256 MUg L-1). Biofiltration of GBCA-s by
      common macrophytes could not be detected in our experiments. Therefore it seems
      that in constructed wetlands, aquatic plants are not able to reduce the
      concentration of GBCA-s in the water. Furthermore there is a low risk that these
      plants cause the accumulation of anthropogenic Gd in the food chain.

PMID- 29459117
TI  - Improving water quality using settleable microalga Ettlia sp. and the bacterial
      community in freshwater recirculating aquaculture system of Danio rerio.
AB  - A highly settleable microalga, Ettlia sp., was applied to a freshwater
      recirculating aquaculture system (RAS) of Danio rerio to improve the treatment of
      nitrogenous compounds. The growth characteristics of the microalgae, water
      quality parameters, and bacterial communities were monitored for 73 days. In the
      treatment RAS, the inoculated Ettlia sp. grew up to 1.26 g/L and dominated (>99%)
      throughout the experiment, whereas naturally occurring microalgae grew to 0.57
      g/L in the control RAS. The nitrate, nitrite, and ammonium concentrations in the
      treatment RAS were reduced by 50.1%, 73.3%, and 24.2%, respectively, compared to
      the control RAS. A bacterial community analysis showed that Rhodospirillales,
      Phycisphaerae, Chlorobiales, and Burkholderiales were the major bacterial groups
      in the later phase of the treatment RAS. Meanwhile, a network analysis among the
      Ettlia sp., bacterial groups, and environmental parameters, revealed that the
      bacterial groups played key roles in both water quality improvement and Ettlia
      sp. growth. In conclusion, the inoculation and growth of the Ettlia sp. and its
      associated bacteria in the RAS produced beneficial effects on the water quality
      by reducing the nitrogenous compounds and providing a favorable environment for
      certain bacterial groups to further improve water quality.

PMID- 29459118
TI  - Aqueous photodegradation of substituted chlorobenzenes: Kinetics, carbon isotope
      fractionation, and reaction mechanisms.
AB  - Substituted chlorobenzenes are the basic substructure of many surface water
      contaminants. In this study, the isotope fractionation and reaction mechanisms
      involved during the aqueous direct and indirect photodegradation of CH3-, Cl-,
      and NO2- substituted chlorobenzenes were investigated in laboratory experiments.
      Only 4-nitrochlorobenzene showed slow but isotopically fractionating direct
      photolysis. During indirect photodegradation using UV/H2O2-generated OH radicals,
      the pseudo first-order reaction rate constants increased in the order of the NO2-
      < Cl- < CH3- substituted chlorobenzenes. The most pronounced carbon enrichment
      factors were observed for nitrochlorobenzenes (up to -4.8 +/- 0.50/00), whereas
      the lowest were for chlorotoluenes (<=-1.0 +/- 0.10/00). As the substituents
      became more electron-withdrawing, the activation energy barrier increased,
      leading to slower reaction rates, and the transition state changed to a more
      symmetrical or less reactant-like structure, resulting in larger apparent kinetic
      isotope effects. The results suggest that the rate-determining step in the
      reaction with OH radicals was the addition of the electrophile to the benzene
      ring. Even though further research is needed to quantify isotope fractionation
      during other transformation processes, these results showed evidence that
      compound specific isotope analysis can be used as a diagnostic tool for the fate
      of substituted chlorobenzenes in water.

PMID- 29459119
TI  - Role of the Nrf2-ARE pathway in perfluorooctanoic acid (PFOA)-induced
      hepatotoxicity in Rana nigromaculata.
AB  - Perfluorooctanoic acid (PFOA) is widely distributed in various environmental
      media and is toxic to organisms. This study demonstrated that PFOA induces
      hepatotoxicity in the frog and evaluated the role of CYP3A and the Nrf2-ARE
      signaling pathway in regulating responses to PFOA-induced hepatotoxicity. Rana
      nigromaculata were exposed to 0, 0.01, 0.1, 0.5, or 1 mg/L PFOA solutions in a
      static-renewal system for 14 days. Liver tissue samples were collected 24 h after
      the last treatment. Hepatic histology was observed by HE staining and
      transmission electron microscopy. The oxidative stress levels in the liver were
      measured. The expression levels of CYP3A, Nrf2, NQO1, and HO-1 mRNA were measured
      by quantitative reverse transcription-polymerase chain reaction. PFOA-treated
      frog liver tissue exhibited diffuse cell borders, cytoplasmic vacuolization,
      broken nuclei, nuclear chromatin margination, and swollen mitochondria. In
      addition, the livers of PFOA-treated frogs showed a significantly elevated
      content of reactive oxygen species, malondialdehyde, glutathione and glutathione
      S-transferase activity compared to the livers of control frogs. However, the
      glutathione peroxidase activities concomitantly decreased in PFOA-treated frogs
      compared to those in the control group. Furthermore, compared with control frogs,
      the expression levels of CYP3A, Nrf2, and NQO1 mRNA significantly increased in
      PFOA-treated frogs. HO-1 mRNA expression remarkably increased only in groups
      treated with 0.5 or 1 mg/L PFOA. Our results indicate that PFOA induces
      hepatotoxicity in a dose-dependent manner. Furthermore, the results of the
      comparison analysis between different gender groups illustrated that PFOA is more
      toxic to female frogs than male frogs. Our results demonstrated that PFOA causes
      liver damage and that CYP3A enhances PFOA-induced female frogs hepatotoxicity are
      more virulent than male through biotransformation, and the activation of the Nrf2
      ARE pathway is induced to protect against hepatotoxicity in Rana nigromaculata,
      all of which provide the scientific basis for the protection of amphibians
      against environmental contaminants.

PMID- 29459120
TI  - Immediate Effects of Core Stabilization Exercise on beta-Endorphin and Cortisol
      Levels Among Patients With Chronic Nonspecific Low Back Pain: A Randomized
      Crossover Design.
AB  - OBJECTIVE: The main objective of the study was to measure the levels of plasma
      beta-endorphin (PB) and plasma cortisol (PC) under lumbar core stabilization
      exercise (LCSE), placebo and control conditions in patients with chronic
      nonspecific low back pain. METHODS: Twenty-four participants with chronic
      nonspecific low back pain participated in a randomized, placebo-controlled,
      crossover design study. There were 3 experimental exercise conditions: control
      condition (positioning in crook lying and rest), placebo condition (passive
      cycling in crook lying using automatic cycler), and LCSE on a Pilates device
      tested with a 48-hour interval between sessions by concealed randomization. A
      blood sample was collected before and after the exercise conditions. Plasma beta
      endorphin and PC were measured through enzyme-linked immunosorbent assay and
      electrochemiluminescence in a Cobas E411 auto analyzer. RESULTS: A significant
      difference in PB level was identified before and after the LCSE condition (P <
      .05), whereas no significant differences were noted in control and placebo
      exercise conditions. Also, the trend of elevation of PB under the LCSE was
      significantly different compared with the placebo and control conditions (P <
      .01). In contrast, the PC level remained unchanged in all 3 conditions.
      CONCLUSION: The findings of this study indicate that LCSE could possibly
      influence PB but not PC level among patients with chronic nonspecific low back
      pain. The mechanism of action of the pain-relieving effect of LCSE might be
      related to an endogenous opioid mechanism as part of its effects and might not be
      involved with a stress-induced analgesia mechanism.

PMID- 29459121
TI  - Effect of Adding Interferential Current in an Exercise and Manual Therapy Program
      for Patients With Unilateral Shoulder Impingement Syndrome: A Randomized Clinical
      Trial.
AB  - OBJECTIVE: The purpose of this study was to measure the additional effect of
      adding interferential current (IFC) to an exercise and manual therapy program for
      patients with unilateral shoulder impingement syndrome. METHODS: Forty-five
      participants were randomly assigned to group 1 (exercise and manual therapy),
      group 2 (exercise and manual therapy + IFC), or group 3 (exercise and manual
      therapy + placebo ultrasound). Individuals participated in 16 treatment sessions,
      twice a week for 8 weeks. The primary outcome of the study was total score of the
      Shoulder Pain and Disability Index (SPADI). The secondary outcomes were the pain
      and disability subscales of SPADI, Numeric Rating Scale, and Pain-Related Self
      Statement Scale. Adjusted between-group mean differences (MDs) and 95% confidence
      intervals (CIs) were calculated using linear mixed models. RESULTS: After 16
      treatment sessions, statistically significant but not clinically important
      differences were identified in favor of the exercise and manual therapy program
      alone in the SPADI-total (group 1 vs group 2, MD 11.12 points, 95% CI 5.90-16.35;
      group 1 vs group 3, MD 13.43 points, 95% CI 8.21-18.65). Similar results were
      identified for secondary outcomes. CONCLUSION: The addition of IFC does not
      generate greater clinical effects in an exercise and manual therapy program for
      individuals with unilateral shoulder impingement syndrome.

PMID- 29459122
TI  - The Association Among Overweight, Obesity, and Low Back Pain in U.S. Adults: A
      Cross-Sectional Study of the 2015 National Health Interview Survey.
AB  - OBJECTIVE: The purpose of this study was to explore the association between
      obesity (via body mass index [BMI]) and presence of low back pain (LBP) in a
      representative sample of US adults, aged >=18 years. METHODS: This cross
      sectional study used data from 32 060 respondents to the 2015 National Health
      Interview Survey. Body mass index (kg/m2) was calculated using reported height
      and weight and expressed as normal weight (<25 kg/m2), overweight (25 to <30
      kg/m2), or obese (>=30 kg/m2); 3-month prevalence of reported LBP was the
      targeted outcome. Weighted univariate and multivariable logistic regression
      (adjusting for age, sex, race/ethnicity, education, and leisure-time physical
      activity) were performed. Interaction by sex and race/ethnicity was also
      explored. RESULTS: Findings suggest a statistically significant association
      between BMI categories and LBP. The adjusted odds ratios (95% confidence
      interval) of LBP in overweight and obese participants were higher than those in
      normal weight participants: 1.21 (1.11-1.32) and 1.55 (1.44-1.67), respectively.
      Both sex and race/ethnicity statistically significantly modified the association
      between BMI and LBP. Compared with normal weight white men (reference), odds
      ratios (95% confidence interval) of LBP were higher among obese white men, obese
      white women, and obese nonwhite women (1.28 [1.10, 1.48], 1.58 [1.36, 1.84], and
      1.36 [1.16, 1.60], respectively), and lower in overweight, nonwhite men, and
      normal weight nonwhite men and women (0.80 [0.68, 0.94], 0.62 [0.51, 0.76], and
      0.73 [0.61, 0.87], respectively). CONCLUSION: Overweight and obesity were
      associated with increased odds of LBP. However, the measures of associations
      varied in magnitude and direction by race and sex groups.

PMID- 29459123
TI  - High-pressure balloon valvuloplasty for severe pulmonary valve stenosis: a
      prospective observational pilot study in 25 dogs.
AB  - OBJECTIVES: We aimed to evaluate safety and efficacy of high-pressure balloon
      valvuloplasty (HPBVP) for treatment of canine severe pulmonary valve stenosis
      (PS). A secondary aim was to provide pre-procedure predictors of success.
      ANIMALS: Twenty-five dogs. METHODS: Prospective observational study. Dogs with
      severe PS (echocardiographically derived trans-pulmonary peak/maximum pressure
      gradient (EDPG) >=80 mmHg) were recruited. All dogs underwent echocardiography
      before and 20-24hrs after HPBVP using a high-pressure balloon with rated burst
      pressures ranging from 12 to 18 ATM. Procedural success was defined as a post
      HPBVP EDPG reduction of >=50% or reduction into at least the moderate category of
      PS (50-79 mmHg). Optimal result was defined as a post-procedural EDPG <=30 mmHg.
      RESULTS: Initial median (IQR) EDPG for all dogs was 96 (88, 127) mmHg with a post
      operative median of 48 (36, 65) mmHg. The median EDPG reduction provided by HPBVP
      was 63% (39, 68); procedural success rate was 92% (23 dogs). Optimal results were
      achieved in 56% (14 dogs). There were no significant correlations between EDPG
      reduction and valve morphology (Type A and Type B) or severity of right
      ventricular hypertrophy. Pulmonary valve annulus diameter was the only
      echocardiographic variable that was significantly correlated to EDPG reduction (p
      = 0.02; r = -0.46). No dog experienced any anesthetic or surgical complications,
      and all patients survived the procedure. CONCLUSIONS: In this cohort of 25 dogs
      with severe PS, HPBVP was safe and effective. The procedural success rate and
      high number of optimal results achieved with HPBVP suggest future randomized
      controlled trials comparing HPBVP to conventional valvuloplasty are warranted.

PMID- 29459124
TI  - Left atrial deformation and phasic function determined by two-dimensional speckle
      tracking echocardiography in dogs with myxomatous mitral valve disease.
AB  - INTRODUCTION: Left atrial (LA) function can provide useful information in dogs
      with myxomatous mitral valve disease (MMVD). Recently, we have demonstrated the
      feasibility of measuring LA longitudinal deformation using speckle-tracking
      echocardiography (STE) to estimate LA function in healthy dogs. Whether LA strain
      and strain rate variables provide additional information about LA function and
      clinical cardiac status in dogs with MMVD remains unexplored. ANIMALS: Ninety-six
      client-owned dogs of different breeds with MMVD were prospectively enrolled.
      METHODS: LA longitudinal deformation was evaluated in each dog by STE and
      different STE variables were used to assess LA function. RESULTS: No STE
      variables differed between American College of Veterinary Internal Medicine Stage
      B1 and B2 dogs but were lower in Stage C dogs. Peak atrial longitudinal average
      strain < 27.9%, left-atrial-to-aortic ratio > 2.2 and peak atrial contraction
      average strain < 7.25% discriminated symptomatic MMVD dogs by receiver operating
      characteristic analysis with sensitivity and specificity of 100% and 100% (95%
      confidence interval [CI] 91-100%), 92% (95% CI 78-98%) and 98% (95% CI 87-100%),
      100% (95% CI 91-100%) and 95% (95% CI 83-99%), respectively. In 12 dogs with
      similar left-atrial-to-aortic ratio, peak atrial longitudinal average strain and
      peak atrial contraction average strain differentiated dogs with subclinical
      disease from those with congestive heart failure (CHF). CONCLUSION: Dogs with
      MMVD in CHF appear to have lower LA longitudinal strain and strain rate variables
      compared with dogs with subclinical disease. Further studies are needed to
      establish if our initial findings can provide useful information for the
      diagnosis, treatment, and prognosis of dogs with MMVD.

PMID- 29459125
TI  - Redescription of Paradiscocyrtus neglectus Mello-Leitao, 1927 (Opiliones:
      Gonyleptidae), with the designation of a neotype and two synonymies.
AB  - Paradiscocyrtus neglectus Mello-Leitao, 1927 is here redescribed and for the
      first time illustrated. A neotype is proposed to clarify the taxonomic status of
      this species and to differentiate it from the other two species of
      Paradiscocyrtus and related genera (e.g., Discocyrtus). Two junior synonyms of
      this species, currently allocated in Discocyrtus Holmberg, 1876 are here
      detected. This harvestman is endemic from areas above 2000 meters of altitude,
      occurring in the Campos Rupestres montane savannas terrestrial eco-region in the
      states of Minas Gerais and Rio de Janeiro, Brazil. This species is characterized
      by the powerful retrodorsal apophysis of the coxa IV, the unique armature of
      dorsal scutum, trochanter IV, and femur IV.

PMID- 29459126
TI  - [Costal periosteal chondrosarcoma: A rare entity].

PMID- 29459127
TI  - [Evaluation of the smoking cessation at the patients of Saint-Denis (Reunion
      island), over the year 2014].
AB  - INTRODUCTION: The fight against smoking is a major challenge for public health in
      Reunion Island. This French overseas department knows considerable social
      inequalities and so there is a possibility of free access to nicotine
      substitution among disadvantaged patients. The objective was to describe the
      social characteristics, the level of addiction to smoking and the actual level of
      smoking cessation at 18 months of tobacco-smoking patients from Reunion who
      consulted in 2014. METHODS: It was an observational, retrospective, monocentric
      study carried out in the addictology service in the teaching hospital in Saint
      Denis, Reunion Island. Inclusion of patients over the year 2014 who were mono
      dependent on tobacco and who were consulting for the first time in order to give
      up smoking. RESULTS: 122 patients were included, 51 % of women, of an average age
      of 47.5 years. The rate of smoking cessation at a year and a half was 23 %. There
      was no significant difference concerning smoking cessation according to the
      patient's level of addiction, the educational level, the profession or the level
      of confidence when stopping. DISCUSSION: The proportion of patients who had given
      up at a year and a half in our study was comparable to the data found in
      international literature. The impact of free access to nicotine substitution on
      smoking cessation could not be estimated.

PMID- 29459128
TI  - Clinical viability of single implant-retained mandibular overdentures: a
      systematic review and meta-analysis.
AB  - The aim of this meta-analysis was to verify the clinical viability of single
      implant-retained mandibular overdentures (SIMO). An electronic search of the
      PubMed and Cochrane databases was performed (end date July 2017); this was
      supplemented by a manual search of the literature. Only prospective clinical
      trials and randomized controlled trials (RCTs) that evaluated SIMO with a minimum
      follow-up of 12 months were included. The meta-analysis was based on the Mantel
      Haenszel method. Dental implant and prosthetic failure were the dichotomous
      outcome measures; these were evaluated through the risk ratio (RR) and odds ratio
      (OR), with corresponding 95% confidence intervals (CI). Of 499 articles
      identified, nine fulfilled the inclusion criteria. A total of 205 implants were
      placed in patients with a mean age of 64.1 years; the cumulative survival rate
      was 96.6% over a mean follow-up period of 37.3 months. The procedure used (SIMO
      vs. two implant-retained mandibular overdenture) did not affect dental implant
      failure (P=0.45) or prosthetic failure (P=0.65): RR 1.06 (95% CI 0.91-1.23) and
      RR 0.88 (95% CI 0.51-1.51), respectively; OR 2.56 (95% CI 0.27-24.39; P=0.41) and
      OR 0.44 (95% CI 0.15-1.26; P=0.13), respectively. Within the limitations of this
      systematic review and meta-analysis, SIMO with a complete denture as the opposing
      arch may be considered an alternative treatment for completely edentulous
      patients. However, this study also confirmed the need for more RCTs on this
      topic.

PMID- 29459129
TI  - Synthesis and biological evaluation of imidazo[2,1-b]thiazole-benzimidazole
      conjugates as microtubule-targeting agents.
AB  - A series of imidazo[2,1-b]thiazole-benzimidazole conjugates were synthesized and
      evaluated for their antiproliferative activity against four human cancer cell
      lines i.e.; HeLa (cervical), A549 (lung), MCF-7 (breast) and DU-145 (prostate)
      along with normal HEK-293 cell line. Amongst them, conjugate 6d displayed
      significant cytotoxicity against human lung cancer cell line, A549 with IC50
      value 1.08 uM. Further, cell cycle analysis revealed that this compound arrested
      the cell cycle at G2/M phase in A549 cells. Furthermore, the tubulin
      polymerization assay results suggest that this conjugate (6d) exhibits
      significant inhibitory effect on the tubulin assembly with an IC50 value of 1.68
      uM. Moreover, the apoptotic inducing properties of compound 6d was confirmed by
      Hoechst staining, measurement of mitochondrial membrane potential (DeltaPsim) and
      annexin V-FITC assay. Further, molecular docking studies revealed that compound
      6d occupied the colchicine binding site.

PMID- 29459130
TI  - Thiazole-substituted benzenesulfonamides as inhibitors of 12 human carbonic
      anhydrases.
AB  - Four series of para or meta - substituted thiazolylbenzenesulfonamides bearing Cl
      substituents were designed, synthesized, and evaluated as inhibitors of all 12
      catalytically active recombinant human carbonic anhydrase (CA) isoforms. Observed
      affinities were determined by the fluorescent thermal shift assay and the
      intrinsic affinities were calculated based on the fractions of binding-ready
      deprotonated sulfonamide and CA bearing protonated hydroxide bound to the
      catalytic Zn(II) in the active site. Several compounds exhibited selectivity
      towards CA IX, an anticancer target. Intrinsic affinities reached 30 pM, while
      the observed affinities - 70 nM. The structure-intrinsic affinity relationship
      map of the compounds showed the energetic contributions of the thiazole ring and
      its substituents.

PMID- 29459131
TI  - Perfluoroalkyl substances, glucose homeostasis, and gestational diabetes mellitus
      in Chinese pregnant women: A repeat measurement-based prospective study.
AB  - BACKGROUND: Exposure to perfluoroalkyl substances (PFASs) can affect glucose
      homeostasis and has been suggested as a potential risk of diabetes mellitus, but
      data are limited for pregnant women. OBJECTIVES: We aimed to explore the
      associations of exposure to PFASs with glucose homeostasis and gestational
      diabetes mellitus (GDM) in Chinese pregnant women. METHODS: The current study was
      conducted in Hebei Province of Northern China between 2013 and 2014 and 560
      pregnant women were recruited in their early term of pregnancy and two
      representative serum PFASs, perfluorooctanoate (PFOA) and perfluorooctane
      sulfonate (PFOS), were measured. In 385 pregnant women who completed oral glucose
      tolerance test (OGTT), the associations of serum PFOA and PFOS concentrations
      with fasting blood glucose (FBG), fasting insulin (FIns), and homeostasis model
      assessment of insulin resistance (HOMA-IR) in the early, middle, and late terms
      of pregnancy and occurrence of GDM were examined using linear and Cox
      proportional hazard regression models. The reproducibility of serum PFASs during
      pregnancy was assessed in 230 pregnant women. RESULTS: The intraclass correlation
      coefficients of serum PFASs, covariates, and outcomes based on averaged repeat
      measurement (0.35-0.96) were higher than those based on single measurement (0.16
      0.92). Serum PFOA was positively associated with averaged FIns and HOMA-IR in the
      early, middle, and late terms of pregnancy and averaged blood glucose level at 1
      h and 2 h of OGTT, but serum PFOS tended to be negatively associated with
      averaged FBG and OGTT blood glucose. The adjusted hazard ratios of GDM associated
      with serum PFOA and PFOS were 1.98 (95% confidence interval: 0.70-5.57; p-value:
      0.197) and 0.71 (0.29-1.75; 0.453), respectively. CONCLUSIONS: Our data raised a
      possibility that exposure to PFASs might have different influences on glucose
      homeostasis and GDM in Chinese pregnant women. More lab and human studies are
      needed to further test the hypothesis and investigate potential mechanisms.

PMID- 29459132
TI  - Implementation of USEPA RfD and SFO for improved risk assessment of
      organophosphate esters (organophosphate flame retardants and plasticizers).

PMID- 29459133
TI  - Screening for Mullerian anomalies in patients with unilateral renal agenesis:
      Leveraging early detection to prevent complications.
AB  - BACKGROUND: Mullerian anomalies have a known association with renal agenesis yet,
      to date, there are no formal recommendations for screening women with certain
      renal anomalies for associated genital tract disorders. OBJECTIVE: The objective
      of this study is to review current data regarding the association between renal
      and Mullerian anomalies, and propose screening recommendations. STUDY DESIGN: A
      comprehensive review of the literature was performed to identify relevant
      articles using the keywords "unilateral renal agenesis," "renal anomalies," and
      "Mullerian anomalies." RESULTS: Over 30% of patients with unilateral renal
      agenesis have an associated Mullerian anomaly. However, diagnosis is frequently
      delayed in this population until after menarche when complications of retrograde
      menstruation with obstructive anomalies lead to significant problems including
      endometriosis, pelvic inflammatory disease, and infertility. No clear guidelines
      exist for communication among the antenatal sonographer, the obstetrician, the
      parents, and the child's pediatrician, which creates a barrier to effective
      screening and follow-up. Further, no current guidelines exist for screening women
      with certain renal anomalies for Mullerian anomalies. DISCUSSION: The
      complications of Mullerian anomalies are easily preventable if identified early.
      We propose new guidelines for education and screening for Mullerian anomalies in
      patients with unilateral renal agenesis (URA) and multicystic dysplastic kidney
      (MCDK) to guide providers, patients, and parents on proper identification and
      management (Table). CONCLUSIONS: Screening young women with URA and MCDK for
      Mullerian anomalies has the potential to prevent long-term complications from
      untreated obstructive malformations. Identification of unilateral renal agenesis
      on antenatal ultrasound must be clearly articulated with parents and the child's
      pediatrician so that proper screening can be performed before menarche. Pelvic
      sonography is a low-cost, high-yield screening tool to identify these anomalies.

PMID- 29459134
TI  - Upper pole access is safe and effective for pediatric percutaneous
      nephrolithotomy.
AB  - INTRODUCTION: Upper pole access in percutaneous nephrolithotomy (PCNL) provides a
      straight tract to the ureter, resulting in easier placement of a guidewire to the
      ureter, good exposure of the pelvis, calices, and upper ureter, and comfortable
      manipulations. However, despite these benefits, upper pole access is usually
      avoided because of the risk of chest complications in both pediatric and adult
      patients. OBJECTIVE: We aimed to evaluate the safety and morbidity of single
      upper pole access in pediatric patients undergoing PCNL. STUDY DESIGN: We
      retrospectively reviewed patients aged <=17 years with renal stones who underwent
      PCNL with a single access between August 2004 and February 2016. The patients
      were separated into two groups: the single upper pole access group (SUPAG) and
      the single other pole access group (SOPAG). We compared the SUPAG and SOPAG in
      terms of the demographic features of the patients, stone burden and location,
      operative data, and postoperative outcomes. Complications were classified
      according to the modified Clavien system. RESULTS: During the study period, 101
      PCNL procedures were performed, 77 of which were managed with only one access.
      The median age of the 77 patients managed with a single access was 12 years
      (range 3-17 years). The number of cases in the SUPAG and SOPAG was 10 and 67,
      respectively. There were no statistically significant differences between the
      SUPAG and SOPAG in terms of age, sex, stone location, hydronephrosis status,
      stone area, side of kidney, and previous stone treatment or renal surgery.
      Furthermoret, there were no significant differences between the groups in terms
      of the operative parameters. Although the difference was insignificant, the
      median operation times in the SUPAG and SOPAG were 37 and 45 min, respectively.
      There was no chest complication or bleeding that required transfusion in the
      SUPAG. Two cases required transfusion, and one case was managed with a double
      pigtail catheter (double-J) placement because of prolonged extravasation in the
      SOPAG. The stone-free ratios were 100% and 82.1% in the SUPAG and SOPAG,
      respectively. CONCLUSION: Upper pole access provides similar outcomes to other
      (middle and lower) pole accesses, and may be performed without serious
      complications. These results indicate that this is a safe and effective approach
      of PCNL, and it presents a good alternative for removal of renal stones in
      pediatric patients.

PMID- 29459135
TI  - Oculosympathetic paresis after selective neck dissection: A 'distant'
      complication.

PMID- 29459136
TI  - Re: RCR audit of compliance with UK guidelines for the prevention and detection
      of acute kidney injury in adult patients undergoing iodinated contrast media
      injections for CT. A reply.

PMID- 29459137
TI  - Microstructural visual pathway abnormalities in patients with primary glaucoma: 3
      T diffusion kurtosis imaging study.
AB  - AIM: To evaluate microstructural visual pathway damage in patients with primary
      glaucoma (PG) by using 3 T diffusion kurtosis imaging (DKI). MATERIALS AND
      METHODS: The study was approved by the ethics committee, and all participants
      provided written informed consent. Ten patients with PG were examined. Twenty
      healthy individuals served as control subjects. DKI was performed with a GE
      Silent 3 T magnetic resonance imaging (MRI) unit. Mean diffusivity (MD),
      fractional anisotropy (FA), and mean kurtosis (MK) maps were automatically
      created. Mean MK, MD, and FA values were calculated for each part of the visual
      pathway. RESULTS: No abnormalities in the shape and signal intensity were
      observed along the entire visual pathway in patients and the control group on the
      conventional MRI. Higher MD, and lower MK and FA were observed in the optic
      nerves (ON), lateral geniculate nucleus (LGN), optic radiations (OR), and visual
      cortex (VCx) of PG patients, as compared with control subjects. A significantly
      higher MD was observed in the ON (p<0.01), and significantly lower FA was
      observed in OR (p<0.05). Additionally, significantly lower MK was observed in the
      ON, LGN, and VCx, except for OR (p<0.01). Changes of DKI parameters in the ON
      were the most distinct. CONCLUSION: Glaucoma is a complex neurological disease
      that affects the entire visual pathway. MK derived from DKI would be a better
      biomarkers than FA and MD in detecting microstructural damage.

PMID- 29459138
TI  - Could early tumour volume changes assessed on morphological MRI predict the
      response to chemoradiation therapy in locally-advanced rectal cancer?
AB  - AIM: To investigate the potential role of an additional magnetic resonance
      imaging (MRI) examination performed during neoadjuvant chemoradiation therapy
      (CRT) in the prediction of pathological response in locally advanced rectal
      cancer (LARC). MATERIAL AND METHODS: Forty-eight consecutive patients with LARC
      underwent neoadjuvant CRT. MRI studies at 1.5 T, including high-resolution T2
      weighted sequences that were acquired parallel and perpendicular to the main axis
      of the tumour were performed before (preMRI), during (midMRI), and 6-8 weeks
      after the end of CRT (postMRI). Cancer volumes (Vpre, Vmid, Vpost) were drawn
      manually and the reduction rate calculated (DeltaVmid, DeltaVpost). According to
      Rodel's pathological tumour regression grade (TRG), patients were considered non
      responders (NR; TRG0-2), partial responders (PR; TRG3), and complete responders
      (CR; TRG4). Multivariate regression analysis was performed to identify the best
      MRI predictors of NR, PR, and CR. RESULTS: Twenty-five patients were considered
      PR (52%), 13 CR (27%), and 10 NR (22%). Tumour shrinkage mainly occurred shortly
      after CRT (DeltaVmid: CR: 80+/-10% versus PR: 56+/-19% versus NR: 28+/-22%,
      p=2.2*10-16). Vmid, Vpost, DeltaVmid, and DeltaVpost correlated with TRG
      (p<0.001). At multivariate analysis, the combined assessment of Vmid and
      DeltaVmid was selected as the best predictor of response to CRT, in that it
      distinguishes CR, PR, and NR early and accurately (81.5%). CONCLUSION: MidMRI
      allows final response assessment to neoadjuvant CRT earlier and better than the
      MRI performed after the end of CRT. MRI findings at midMRI may be useful to
      tailor patient treatment.

PMID- 29459139
TI  - Right adrenal vein: comparison between adaptive statistical iterative
      reconstruction and model-based iterative reconstruction.
AB  - AIM: To compare right adrenal vein (RAV) visualisation and contrast enhancement
      degree on adrenal venous phase images reconstructed using adaptive statistical
      iterative reconstruction (ASiR) and model-based iterative reconstruction (MBIR)
      techniques. MATERIAL AND METHODS: This prospective study was approved by the
      institutional review board, and written informed consent was waived. Fifty-seven
      consecutive patients who underwent adrenal venous phase imaging were enrolled.
      The same raw data were reconstructed using ASiR 40% and MBIR. The expert and
      beginner independently reviewed computed tomography (CT) images. RAV
      visualisation rates, background noise, and CT attenuation of the RAV, right
      adrenal gland, inferior vena cava (IVC), hepatic vein, and bilateral renal veins
      were compared between the two reconstruction techniques. RESULTS: RAV
      visualisation rates were higher with MBIR than with ASiR (95% versus 88%, p=0.13
      in expert and 93% versus 75%, p=0.002 in beginner, respectively). RAV
      visualisation confidence ratings with MBIR were significantly greater than with
      ASiR (p<0.0001, both in the beginner and the expert). The mean background noise
      was significantly lower with MBIR than with ASiR (p<0.0001). Mean CT attenuation
      values of the RAV, right adrenal gland, IVC, and hepatic vein were comparable
      between the two techniques (p=0.12-0.91). Mean CT attenuation values of the
      bilateral renal veins were significantly higher with MBIR than with ASiR
      (p=0.0013 and 0.02). CONCLUSION: Reconstruction of adrenal venous phase images
      using MBIR significantly reduces background noise, leading to an improvement in
      the RAV visualisation compared with ASiR.

PMID- 29459140
TI  - Corrigendum to "Assessment of quality of life on 4-year growth hormone therapy in
      Japanese patients with adult growth hormone deficiency: A post-marketing,
      multicenter, observational study" [Growth Hormon. IGF Res. 36 (2017) 36-43].

PMID- 29459141
TI  - A descriptive study on selected growth parameters and growth hormone receptor
      gene in healthy young adults from the American Midwest.
AB  - CONTEXT: The first study of growth hormone receptor (GHR) genotypes in healthy
      young adults in the United States attending a Midwestern university and impact on
      selected growth parameters. OBJECTIVE: To describe the frequency of GHR genotypes
      in a sample of healthy young adults from the United States attending a university
      in the Midwest and analyze the relationship between GHR genotypes and selected
      growth parameters. DESIGN: Saliva was collected from 459 healthy young adults
      (237 females, 222 males; age range = 18-25 y) and DNA isolated for genotyping of
      GHR alleles (fl/fl, fl/d3, or d3/d3). Selected growth parameters were collected
      and GHR genotype data examined for previously reported associations (e.g.,
      height, weight or bone mass density) or novel findings (e.g., % body water and
      index finger length). RESULTS: We found 219 participants (48%) homozygous for
      fl/fl, 203 (44%), heterozygous fl/d3 and 37 (8%) homozygous d3/d3. The
      distribution of GHR genotypes in our participants was consistent with previous
      reports of non-US populations. Several anthropometric measures differed by sex.
      The distribution of GHR genotypes did not significantly differ by sex, weight, or
      other anthropometric measures. However, the fl/d3 genotype was more common among
      African-Americans. CONCLUSIONS: Our study of growth and anthropometric parameters
      in relationship to GHR genotypes found no association with height, weight, right
      index finger length, BMI, bone mass density, % body fat or % body water in
      healthy young adults. We did identify sex differences with increased body fat,
      decreased bone density, body water and index finger length in females.

PMID- 29459142
TI  - Modulation of human corticospinal excitability by paired associative stimulation
      in patients with amyotrophic lateral sclerosis and effects of Riluzole.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
      that causes an impairment in both the upper and lower motor neurons. The recent
      description of numerous non-motor signs points to an involvement of the neocortex
      networks that is more complex than was previously believed. Paired associative
      stimulation (PAS), a combination of transcranial magnetic stimulation (TMS) and
      peripheral nerve stimulation, can enhance motor output in the contralateral hand
      through an NMDA-mediated sensorimotor mechanism. OBJECTIVE: To describe the
      effects of PAS on ALS patients before and after Riluzole intake compared with
      healthy subjects. METHODS: PAS was used to detect differences between 24 newly
      diagnosed ALS patients and 25 age-matched healthy controls. MEP amplitude from
      the abductor pollicis brevis was considered before PAS, immediately after (T0)
      and after 10 (T10), 20 (T20), 30 (T30) and 60 (T60) minutes. Statistical
      significance was calculated using RM-ANOVA. RESULTS: In healthy controls, PAS
      significantly increased MEP amplitude at T10, T20 and T30 (p < 0.05). In ALS
      patients, a significant increase in MEP amplitude was also observed after 60 min
      (p < 0.05), thus demonstrating NMDA-mediated enhanced facilitatory plasticity.
      After two weeks of riluzole intake, no MEP amplitude increase was evident after
      PAS at any time point. In three monomelic-onset ALS patients, a long lasting
      sensorimotor facilitation was evident only in the hemisphere corresponding to the
      affected side and appeared in the opposite hemisphere when the patients
      manifested contralateral symptoms. CONCLUSIONS: PAS may be considered a useful
      tool when investigating NMDA-mediated neocortical networks in ALS patients and
      the modulation of such networks after anti-glutamatergic drug intake.

PMID- 29459143
TI  - ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus
      Document on the safety of targeted and biological therapies: an infectious
      diseases perspective (Soluble immune effector molecules [I]: anti-tumor necrosis
      factor-alpha agents).
AB  - BACKGROUND: The present review is part of the ESCMID Study Group for Infections
      in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and
      biological therapies. AIMS: To review, from an Infectious Diseases perspective,
      the safety profile of agents targeting tumour necrosis factor-alpha (TNF-alpha)
      and to suggest preventive recommendations. SOURCES: Computer-based MEDLINE
      searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT:
      Preclinical and clinical evidence indicate that anti-TNF-alpha therapy
      (infliximab, adalimumab, golimumab, certolizumab pegol and etanercept) is
      associated with a two-to four-fold increase in the risk of active tuberculosis
      and other granulomatous conditions (mostly resulting from the reactivation of a
      latent infection). In addition, it may lead to the occurrence of other serious
      infections (bacterial, fungal, opportunistic and certain viral infections). These
      associated risks seem to be lower for etanercept than other agents. Screening for
      latent tuberculosis infection should be performed before starting anti-TNF-alpha
      therapy, followed by anti-tuberculosis therapy if appropriate. Screening for
      chronic hepatitis B virus (HBV) infection is also recommended, and antiviral
      prophylaxis may be warranted for hepatitis B surface antigen-positive
      individuals. No benefit is expected from the use of antibacterial, anti
      Pneumocystis or antifungal prophylaxis. Pneumococcal and age-appropriate
      antiviral vaccinations (i.e. influenza) should be administered. Live-virus
      vaccines (i.e. varicella-zoster virus or measles-mumps-rubella) may be
      contraindicated in people receiving anti-TNF-alpha therapy, although additional
      data are needed before definitive recommendations can be made. IMPLICATIONS:
      Prevention measures should be implemented to reduce the risk of latent
      tuberculosis or HBV reactivation among individuals receiving anti-TNF-alpha
      therapy.

PMID- 29459144
TI  - Discovery of novel 4-aryl-thieno[1,4]diazepin-2-one derivatives targeting
      multiple protein kinases as anticancer agents.
AB  - A series of 4-aryl-thieno[1,4]diazepin-2-one were synthesized and evaluated for
      their antiproliferative activities against the A375P melanoma and U937
      hematopoietic cell lines. Several compounds showed very potent antiproliferative
      activities toward both cell lines and the activities were better than that of
      sorafenib, the reference standard. Derivatives were made as amide (8a-8i, 9a-9m)
      and urea (10a-10d, 11a-11d) with diverse hydrophobic moieties. One of the most
      potent inhibitor 10d, 1-(4-((4-ethylpiperazin-1-yl)methyl)-3
      (trifluoromethyl)phenyl)-3-(4-(2-oxo-2,3-dihydro-1H-thieno [3,4-b][1,4]diazepin-4
      yl)phenyl)urea was found to be very potent inhibitor of multi-protein kinases
      including FMS kinase (IC50 = 3.73 nM) and is a promising candidate for further
      development in therapeutics for cancer.

PMID- 29459145
TI  - Discovery of 1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoles as novel class of
      corticotropin releasing factor 1 receptor antagonists.
AB  - A new class of corticotropin releasing factor 1 (CRF1) receptor antagonists
      characterized by a tricyclic core ring was designed and synthesized. Novel
      tricyclic derivatives 2a-e were designed as CRF1 receptor antagonists based on
      conformation analysis of our original 2-anilinobenzimidazole CRF1 receptor
      antagonist. The synthesized tricyclic derivatives 2a-e showed CRF1 receptor
      binding activity with IC50 values of less than 400 nM, and the 1,2,3,4
      tetrahydropyrimido-[1,2-a]benzimidazole derivative 2e was selected as a lead
      compound with potent in vitro CRF1 receptor binding activity (IC50 = 7.1 nM). To
      optimize the pharmacokinetic profiles of lead compound 2e, we explored suitable
      substituents on the 1-position and 6-position, leading to the identification of
      compound 42c-R, which exhibited potent CRF1 receptor binding activity (IC50 = 58
      nM) with good oral bioavailability (F = 68% in rats). Compound 42c-R exhibited
      dose-dependent inhibition of [125I]-CRF binding in the frontal cortex (5 and 10
      mg/kg, p.o.) as well as suppression of locomotor activation induced by
      intracerebroventricular administration of CRF in rats (10 mg/kg, p.o.). These
      results suggest that compound 42c-R successfully binds CRF1 receptors in the
      brain and exhibits the potential to be further examined for clinical studies.

PMID- 29459146
TI  - 2-Arylthio-5-iodo pyrimidine derivatives as non-nucleoside HBV polymerase
      inhibitors.
AB  - In this study, a series of 2-arylthio-5-iodo pyrimidine derivatives, as non
      nucleoside hepatitis B virus inhibitors, were evaluated and firstly reported as
      potential anti-HBV agents. To probe the mechanism of active agents, DHBV
      polymerase was isolated and a non-radioisotopic assay was established for
      measuring HBV polymerase. The biological results demonstrated that 2-arylthio-5
      iodo pyrimidine derivatives targeted HBV polymerase. In addition, pharmacophore
      models were constructed for future optimization of lead compounds. Further study
      will be performed for the development of non-nucleoside anti-HBV agents.

PMID- 29459147
TI  - CycLS: Accurate, whole-library sequencing of cyclic peptides using tandem mass
      spectrometry.
AB  - Cyclic peptides are of great interest as therapeutic compounds due to their
      potential for specificity and intracellular activity, but specific compounds can
      be difficult to identify from large libraries without resorting to molecular
      encoding techniques. Large libraries of cyclic peptides are often DNA-encoded or
      linearized before sequencing, but both of those deconvolution strategies
      constrain the chemistry, assays, and quantification methods which can be used. We
      developed an automated sequencing program, CycLS, to identify cyclic peptides
      contained within large synthetic libraries. CycLS facilitates quick and easy
      identification of all library-members via tandem mass spectrometry data without
      requiring any specific chemical moieties or modifications within the library.
      Validation of CycLS against a library of 400 cyclic hexapeptide peptoid hybrids
      (peptomers) of unique mass yielded a result of 95% accuracy when compared against
      a simulated library size of 234,256 compounds. CycLS was also evaluated by
      resynthesizing pure compounds from a separate 1800-member library of cyclic
      hexapeptides and hexapeptomers with high mass redundancy. Of 22 peptides
      resynthesized, 17 recapitulated the retention times and fragmentation patterns
      assigned to them from the whole-library bulk assay results. Implementing a
      database-matching approach, CycLS is fast and provides a robust method for
      sequencing cyclic peptides that is particularly applicable to the deconvolution
      of synthetic libraries.

PMID- 29459148
TI  - Editor's Perspectives - February 2018.

PMID- 29459149
TI  - Root Canal Irrigants and Medicaments in Endodontic Malpractice Cases: A
      Nationwide Longitudinal Observation.
AB  - INTRODUCTION: The aim of this study was to assess the role of root canal
      irrigants and medicaments in endodontic injuries verified in Finland and to
      estimate the rate of such events over time. METHODS: The study material comprised
      all endodontic injuries verified by the Patient Insurance Centre in 2002 to 2006
      (n = 521) and 2011 to 2013 (n = 449). The data, based on patient documents
      scrutinized by 2 specialists in endodontics, included patients' and dentists' sex
      and age and the service sector. We recorded the use of root canal irrigants and
      medicaments, each as a dichotomy. Furthermore, we dichotomized the injuries as
      those related to root canal irrigants/medicaments and any other injuries. The
      injuries were also dichotomized as avoidable (could have been avoided by
      following good clinical practice) or unavoidable (normal treatment-related
      risks). Statistical evaluation used chi-square tests and t tests; logistic
      regression produced odds ratios (ORs). RESULTS: The verified injuries (N = 970)
      comprised 635 (65%) avoidable and 335 (35%) unavoidable injuries. The number of
      irrigant-/medicament-related injuries was 69, accounting for 7.1% of all verified
      injuries; all resulted from sodium hypochlorite and calcium hydroxide, and 87%
      were avoidable. The overall rate of sodium hypochlorite/calcium hydroxide
      injuries was 4.3 cases per 100,000 endodontic patients per year. Compared with
      other injuries, sodium hypochlorite/calcium hydroxide injuries were more likely
      avoidable (OR = 3.8) and more than 5-fold likely in 2011 to 2013 than in 2002 to
      2006 (OR = 5.6). CONCLUSIONS: Extreme care is needed when applying sodium
      hypochlorite and calcium hydroxide into root canals to avoid increasing harmful
      consequences.

PMID- 29459150
TI  - Anesthetic Efficacy of a Combination of 4% Prilocaine/2% Lidocaine with
      Epinephrine for the Inferior Alveolar Nerve Block: A Prospective, Randomized,
      Double-blind Study.
AB  - INTRODUCTION: Prilocaine plain has a high pH and concentration (4%), which could
      decrease the pain of injection and increase success. The purpose of this study
      was to compare pain associated with anesthetic solution deposition and the degree
      of pulpal anesthesia obtained with the combination of prilocaine and lidocaine
      versus a lidocaine and lidocaine combination when used for inferior alveolar
      nerve blocks (IANBs). METHODS: One hundred eighteen asymptomatic subjects were
      randomly given a combination of 1 cartridge of 4% prilocaine plain plus 1
      cartridge of 2% lidocaine with 1:100,000 epinephrine or a combination of 2
      cartridges of 2% lidocaine with 1:100,000 epinephrine for the IANB at 2 separate
      appointments. Subjects rated the pain associated with anesthetic solution
      deposition of injection. Mandibular teeth were tested with an electric pulp
      tester every 4 minutes for 57 minutes. Anesthesia was considered successful when
      2 consecutive 80 readings were obtained within 17 minutes and the 80 reading was
      continuously sustained for 57 minutes. Comparisons for anesthetic success were
      analyzed using the exact McNemar test, and pain ratings associated with
      anesthetic solution deposition were analyzed using multiple Wilcoxon matched
      pairs signed rank tests; both were adjusted using the step-down Bonferroni method
      of Holm. RESULTS: Four percent prilocaine plain was significantly less painful
      upon anesthetic solution deposition. Pulpal anesthetic success was not
      significantly different between the 2 combinations. CONCLUSIONS: The combination
      of 4% prilocaine plain plus 2% lidocaine with 1:100,000 epinephrine did not
      increase pulpal anesthetic success for IANBs compared with a combination of 2
      cartridges of 2% lidocaine with 1:100,000 epinephrine. Pain associated with
      anesthetic solution deposition from the first cartridge of 4% prilocaine plain
      was significantly less when compared with the first cartridge of 2% lidocaine
      with 1:100,000 epinephrine.

PMID- 29459151
TI  - Biomechanical Effects of Bonding Pericervical Dentin in Maxillary Premolars.
AB  - INTRODUCTION: Pericervical dentin (PCD) loss may increase root fracture
      propensity in root-filled teeth. This study evaluated the impacts of bonding PCD
      with composite resin (CR) on radicular microstrain distribution and load at
      failure of root-filled maxillary premolars. METHODS: Ten single-canal maxillary
      premolars decoronated 2 mm coronal to the cementoenamel junction (CEJ) had canals
      enlarged with ProTaper Universal instruments (Dentsply Tulsa Dental Specialties,
      Tulsa, OK) to F3. They were root filled with gutta-percha (GP) to the CEJ and
      restored with Cavit (3M Deutschland GmbH, Neuss, Germany) (GP group, n = 5) or 6
      mm apical to the CEJ and restored with bonded CR to simulate bonding of PCD
      (bonded PCD group, n = 5). Digital moire interferometry was used to evaluate pre-
      and postoperative whole-field microstrain distribution in the root dentin under
      physiologically relevant loads (10-50 N). Another 30 premolars, similarly treated
      as groups 1 and 2 or left untreated as controls (n = 10/group), were subjected to
      cyclic loads (1.2 million cycles, 45 N, 4 Hz) followed by uniaxial compressive
      load to failure. Mechanical data were analyzed with 1-way analysis of variance
      and the post hoc Tukey test at a 5% level of significance. RESULTS: Microstrain
      distribution showed bending and compressive patterns at the coronal and apical
      root dentin, respectively. In the GP group, microstrain distribution was
      unaltered. In the bonded-PCD group, different microstrain distribution suggested
      stiffening at the PCD. The load at failure did not differ significantly for the
      GP, bonded PCD, and control groups (P > .05). CONCLUSIONS: CR bonding of PCD
      might impact the biomechanical responses in maxillary premolar roots at low-level
      continuous loads. The effect of this impact on root fracture loads when subjected
      to cyclic load warrants further investigation.

PMID- 29459152
TI  - Dose-response curves for MRI-detected radiation-induced temporal lobe reactions
      in patients after proton and carbon ion therapy: Does the same RBE-weighted dose
      lead to the same biological effect?
AB  - PURPOSE: To derive the dose-response curve for temporal lobe reactions (TLRs)
      after proton therapy and to compare the resulting relative biological
      effectiveness (RBE)-weighted tolerance doses based on an RBE of 1.1 with
      published values for carbon ions, which were calculated by the two versions of
      the local effect model (LEM I or IV). METHODS AND MATERIALS: 62 patients treated
      with protons for skull base tumors were analyzed for TLRs using magnetic
      resonance imaging. Within the mean follow-up time of 38 months, TLRs were
      observed in six patients. Dose-response curves based on the RBE-weighted maximum
      dose, excluding the 1 cm3-volume with the highest dose, were derived and compared
      to previously published dose-response curves for carbon ions, which were obtained
      using LEM I or IV, respectively. RESULTS: The dose-response curves for protons
      and LEM I were found to be almost identical while the curve of LEM IV was shifted
      toward higher doses. The resulting tolerance doses at the 5% effect level were
      68.2+2.7-5.6, 68.6+3.0-3.9 and 78.3+3.8-5.0 Gy (RBE), respectively. CONCLUSIONS:
      The RBE-weighted dose prescription for protons leads to the same RBE-weighted
      dose-response curve for TLR as the one for LEM I-based carbon ions, while LEM IV
      predicts clinically significant higher tolerance doses.

PMID- 29459153
TI  - A statistical comparison of motion mitigation performances and robustness of
      various pencil beam scanned proton systems for liver tumour treatments.
AB  - BACKGROUND AND PURPOSE: Different scanned proton therapy systems provide
      different scanning scenarios, directly changing the temporal interference between
      sequential beam delivery and tumour motion. We aim here to quantify the interplay
      effects and compare motion mitigation performance among different PBS scanning
      systems. MATERIALS AND METHODS: Using 6 4DCT(MRI) datasets of liver tumours with
      irregular motions greater than 10 mm, 4D treatments with single- and double-field
      plans, and assuming various doses and motion mitigation approaches, were
      simulated for 8 PBS scenarios including spot or raster scanning, layered or
      volumetric rescanning, gating, constant or varying beam current and cyclotron or
      synchrotron beam sources. The resulting 4D plans were compared using the
      homogeneity index (D5-D95 in CTV) and treatment time. RESULTS: Independent of
      scanning scenario and field dose, neither gating nor rescanning alone could
      mitigate motion effects completely. Re-gating (rescanning with gating) however
      was found to be similarly effective for all scanning scenarios, most field doses
      and both rescan modes, with the difference being mainly in the treatment
      efficiency. The advantage of cyclotron-based systems together with layer-by-layer
      beam current variation was demonstrated by the nearly constant treatment time as
      a function of increased field dose. CONCLUSION: Independently of PBS scanning
      dynamics, re-gating is sufficient to achieve acceptable 4D plan quality close to
      those of the static references.

PMID- 29459154
TI  - Effect of different types of dental anchorage following first premolar extraction
      on mandibular third molar angulation.
AB  - OBJECTIVES: The aim of this study was to determine the effect of first premolar
      extraction with different anchorages as well as non-extraction on mandibular
      third molar angulation. MATERIALS AND METHODS: The pretreatment (T1) and
      posttreatment (T2) panoramic radiographs of one hundred patients from Hamadan
      (Iran), who underwent fixed orthodontic treatment were investigated and the angle
      between long axis of right mandibular third molars and a constructed horizontal
      plan (HRP) was measured. The sample was equally divided into four groups
      including first premolar extraction with maximum anchorage, that with moderate
      anchorage, that with minimum anchorage and non-extraction group. RESULTS: In the
      first premolar extraction groups with moderate and minimum anchorages, third
      molar angulation increased (8.12 and 7.48 degrees , respectively) significantly
      from T1 to T2 (P=0.001 and 0.003, respectively), but in the first premolar
      extraction group with maximum anchorage and non-extraction group, increase in
      third molar angulation (2.84 and 0.8 degrees , respectively) was not
      statistically significant (P=0.082 and 0.943, respectively). Third molar
      uprighting was significantly different among four groups using one-way ANOVA
      (P=0.004). Tukey (HSD: honestly significant difference) post hoc test indicated
      that difference in third molar angulation was statistically significant between
      first premolar extraction group with moderate anchorage and non-extraction group
      (P=0.007) and also between the first premolar extraction group with minimum
      anchorage and non-extraction group (P=0.024). CONCLUSION: The first premolar
      extraction groups with moderate and minimum anchorage may lead to more chance of
      third molar eruption and this can be helpful in borderline cases to consider
      third molar angulation as one of determining indicators to decide whether to
      extract or not to extract first premolars.

PMID- 29459155
TI  - Decreased bone density induced by antiepileptic drugs can cause accelerated
      orthodontic tooth movement in male Wistar rats.
AB  - PURPOSE: The aim of the present study was to evaluate the effect of the
      carbamazepine and valproic acid on orthodontic tooth movement in male Wistar
      rats. METHODS: Evaluation of tooth movement after 21 days of drugs infusion was
      carried out by feeler gauge. Bone densitometry on lateral cephalograms was
      conducted on days 1 and 21. After dissection of the maxillae, histologic
      parameters were evaluated. RESULTS: Orthodontic tooth movement was accelerated in
      experimental groups rather than controls. Optical density was significantly
      increased in these groups. In histologic sections, mesioapical portion of the PDL
      (Periodontal Ligament) was wider in experimental groups. Also, distoapical
      portion of the PDL was wider only in valproic acid group. CONCLUSION: Valproic
      acid and carbamazepine can decrease the bone density which may induce the
      accelerated orthodontic tooth movement in rats.

PMID- 29459156
TI  - ?

PMID- 29459157
TI  - ?

PMID- 29459158
TI  - Characterization of Co and Fe-MCM-56 catalysts for NH3-SCR and N2O decomposition:
      An in situ FTIR study.
AB  - Two-step preparation of iron and cobalt-containing MCM-56 zeolites has been
      undertaken to evaluate the influence of their physicochemical properties in the
      selective catalytic reduction (NH3-SCR or DeNOx) of NO using NH3 as a reductant.
      Zeolites were prepared by the selective leaching of the framework cations by
      concentrated HNO3 solution and NH4F/HF mixture and consecutively, introduction of
      Co and Fe heteroatoms, in quantities below 1wt%. Further calcination allowed to
      obtain highly dispersed active species. Their evaluation and speciation was
      realized by adsorption of pyridine and NO, followed by FTIR spectroscopy. Both Fe
      MCM-56 zeolites showed excellent activities (maximum NO conversion 92%) with high
      selectivity to dinitrogen (above 99%) in the high temperature NH3-SCR process.
      High catalytic activity of Fe-MCM-56 zeolites was assigned to the formation of
      stable nitrates, delivering NO to react with NH3 at higher temperatures and
      suppressing the direct NO oxidation. It was found that more nitrates was formed
      in Fe-MCM-56 (HNO3) than in Fe-MCM-56 (HF/NH4F) and that could compensate for the
      lower Fe loading, resulting in very similar catalytic activity of both catalysts.
      At the same time both Co-and Fe-MCM-56 zeolites were moderately active in direct
      N2O decomposition, with maximum N2O conversion not higher than 80% and activity
      window starting at 500 degrees C. This phenomenon was expected since both types
      of catalysts contained well dispersed active centers, not beneficial for this
      reaction.

PMID- 29459159
TI  - Structural sensitivity of CH vibrational band in methyl benzoate.
AB  - The CH vibrational bands of methyl benzoate are studied to understand its
      coupling pattern with other vibrational bands of the biological molecule. This
      will facilitate to understand the biological structure and dynamics in
      spectroscopic as well as in microscopic study. Due to the congested spectroscopic
      pattern, near degeneracy, and strong anharmonicity of the CH stretch vibrations,
      assignment of the CH vibrational frequencies are often misleading. Anharmonic
      vibrational frequency calculation with multidimensional potential energy surface
      interprets the CH vibrational spectra more accurately. In this article we have
      presented the importance of multidimensional potential energy surface in
      anharmonic vibrational frequency calculation and discuss the unexpected red shift
      of asymmetric CH stretch vibration of methyl group. The CD stretch vibrational
      band which is splitted to double peaks due to the Fermi resonance is also
      discussed here.

PMID- 29459160
TI  - Antimicrobial activity, cytotoxicity and DNA binding studies of carbon dots.
AB  - In recent years, quantum dots (QDs) are one of the most promising nanomaterials
      in life sciences community due to their unexploited potential in biomedical
      applications; particularly in bio-labeling and sensing. In the advanced
      nanomaterials, carbon dots (CDs) have shown promise in next generation bioimaging
      and drug delivery studies. Therefore the knowledge of the exact nature of
      interaction with biomolecules is of great interest to designing better
      biosensors. In this study, the interaction between CDs derived from tamarind and
      calf thymus DNA (ct-DNA) has been studied by vital spectroscopic techniques,
      which revealed that the CDs could interact with DNA via intercalation. The
      apparent association constant has been deduced from the absorption spectral
      changes of ct-DNA-CDs using the Benesi-Hildebrand equation. From the DNA induced
      emission quenching experiments the apparent DNA binding constant of the CDs
      (Kapp) have also been evaluated. Furthermore, we have analyzed the antibacterial
      and antifungal activity of CDs using disc diffusion assay method which exhibited
      excellent activity against E. coli and C. albicans with inhibition zone in the
      range of 7-12mm. The biocompatible nature of CDs was confirmed by an in vitro
      cytotoxicity test on L6 normal rat myoblast cells by using MTT assay. The cell
      viability is not affected till the high dosage of CDs (200MUg/mL) for >48h. As a
      consequence of the work, future development of CDs for microbial control and DNA
      sensing among the various biomolecules is possible in view of emerging biofields.

PMID- 29459161
TI  - Mercury concentration and the absolute and relative sizes of the internal organs
      in cormorants Phalacrocorax carbo (L. 1758) from the breeding colony by the
      Vistula Lagoon (Poland).
AB  - This work analyses the effect of mercury on the condition of cormorants
      (Phalacrocorax carbo) from an extensive breeding colony in northern Poland, the
      largest in Europe. A total of 55 birds (44 adults and 11 immature) were obtained.
      Total mercury (Hg) concentrations were measured in the liver, kidneys, breast
      muscles, heart, gullet (oesophagus), stomach, intestines, trachea, lungs and
      eyeballs. The total body mass (TBM) and empty body mass (EBM) were measured, and
      the body parts taken for analysis were weighed. The relative mass of the tissues
      and the L/K index were expressed as percentages. Based on the L/K index the birds
      were divided into three condition classes: (A) very good, (B) good and (C)
      moderate. The mean TBM and EBM in these cormorants were 2286 and 2184 g
      respectively. The greatest contributions to EBM were from the breast muscles
      (~11%), liver (3.7%) and intestines (3.0%). The stomach, gullet, lungs, heart and
      kidneys made up from ~1.0-2.8% EBM, and the trachea and eyeballs < 0.4%. 31 of
      the 55 birds analysed were allocated to class B; mean Hg levels in them were the
      highest in the kidneys, liver, lungs and muscles (18.3, 9.78, 2.70, 1.86 ug/g dw
      respectively); they were <= 1 ug/g in the other tissues. In ecotoxicology it is
      assumed that a hepatic concentration > 16.7 ug Hg/g dw can lead to adverse
      effects in the reproduction of non-marine birds. In the light of the present
      results, the reproductive parameters of the cormorants from the colony in
      northern Poland, though mostly in good or very good condition, may be depressed
      as a result of elevated Hg levels in their body tissues.

PMID- 29459162
TI  - Enrichment, spatial distribution of potential ecological and human health risk
      assessment via toxic metals in soil and surface water ingestion in the vicinity
      of Sewakht mines, district Chitral, Northern Pakistan.
AB  - This study focuses on enrichment, spatial distribution, potential ecological risk
      index (PERI) and human health risk of various toxic metals taken via soil and
      surface water in the vicinity of Sewakht mines, Pakistan. The samples of soils (n
      = 54) of different fields and surface water (n = 38) were analyzed for toxic
      metals including cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron
      (Fe), manganese (Mn), lead (Pb), nickel (Ni), zinc (Zn) and molybdenum (Mo). Soil
      pollution level was evaluated using pollution indices including geo-accumulation
      index (Igeo), contamination factor (CF), degree of contamination (CD), enrichment
      factor (EF) and PERI. CF showed moderate contamination of soil with Cd, Co, Fe
      and Mo, while Igeo values indicated moderate accumulation of Cu. For Cd, EF> 1.5
      was found in agricultural soils of the study area. PERI findings presented a very
      high ecological risk (PERI > 380) at two sites (4%), considerable ecological risk
      at four sites (7.4%). Non-carcinogenic risk from exposure to Fe in soil was
      higher than limit (HI > 1) for both children and adults. Moreover, carcinogenic
      risk postured by soil contaminants i.e. Cd, Cr, Co and Ni in children was higher
      than their limits (except Pb), while in adults only Co posed higher risk of
      cancer than the limit (10-4) through soil exposure. Non-carcinogenic risks in
      children due to Cd, Co, Mo via surface water intake were higher than their safe
      limits (HQ > 1), while in adults the risk order was Cr > Cd > Cu > Pb > Co > Mo.
      Moreover, carcinogenic risk exposure due to Co > Cd > Cr > Ni from surface water
      (except Pb) was higher than the tolerable limit (1 * 10-4) both for children and
      adults. However, Pb concentrations in both soil and surface water exposure were
      not likely to cause cancer risk in the local population.

PMID- 29459163
TI  - Se enhanced phytoremediation of diesel in soil by Trifolium repens.
AB  - A pot-culture experiment was conducted to assess the effects of selenium (Se)
      (0.5 mg kg-1) on Trifolium repens exposed to various levels of diesel (0, 15, 20,
      25 g kg-1) for 30 days and 60 days. Exposure to diesel for 60 day led to
      concentration-dependent decreases in root morphogenesis, chlorophyll content and
      CAT activity, and to dose-dependent increases in MDA content and SOD activity.
      The residual diesel concentration in soil increased and the removal efficiency
      decreased with soil diesel concentration. The chlorophyll content and residual
      diesel concentration after were slightly higher at 30 days than at 60days.
      Application of Se to soil increased Trifolium repens tolerance to diesel and
      significantly increased the phytoremediation effect at 60 days, with a removal
      rate of 36 +/- 8%, compared to 28 +/- 7% in the control. These results contribute
      to the ongoing effort to develop an effective phytoremediation system for soils
      highly contaminated by diesel.

PMID- 29459164
TI  - Synergistic effect of co-exposure to cadmium (II) and 4-n-nonylphenol on growth
      inhibition and oxidative stress of Chlorella sorokiniana.
AB  - Toxicological effect of freshwater algae co-exposure to Cd and 4-n-nonylphenol (4
      n-NP) was seldom reported. In the present study, Chlorella sorokiniana was
      selected for testing the single and combined effect of Cd and 4-n-NP by detecting
      the growth inhibition and oxidative stress after exposure for 48 h, 72 h, and 96
      h. The combined effects were evaluated by using toxic units (TU) method and
      concentration addition(CA)model. The synergistic effect of mixture on algal
      growth inhibition was both observed at 48 h and 72 h, and the additive effect was
      observed at 96 h. In addition, the significant alterations of superoxide,
      thiobarbituric acid reactive substances and antioxidant defenses (superoxide
      dismutase, catalase, glutathione) have been detected. It could be observed that
      the mixture predominantly lead to synergistic effects in superoxide induction,
      and the antagonistic effects in the GSH induction. A similar trend between the
      superoxide induction and growth inhibition were observed, which may indicate that
      the oxidative effects of Chlorella sorokiniana contributed to the growth
      inhibition after exposure to Cd and 4-n-NP. These findings may have important
      implications in the risk assessments of heavy metals and endocrine disruptors in
      the aquatic environment.

PMID- 29459165
TI  - House sparrow biomarkers as lead pollution bioindicators. Evaluation of dose and
      exposition length on hematological and oxidative stress parameters.
AB  - House sparrows (Passer domesticus) have been proposed as a key ecological
      indicator of urban pollution. Remarkably, we lack knowledge about the
      physiological effects of lead on this bird species. Therefore, this study was
      aimed to evaluate the effect of Pb on several physiological parameters in house
      sparrows exposed to environmental Pb concentrations. In a first experiment, birds
      were exposed to Pb sub-lethal doses (from 1.3 to 14.0 ug of Pb/g animal/day)
      during 5 days, which resulted in a dose response increase of blood Pb levels and
      decrease of blood ALAD activity. However, at the higher doses tested (> 7 MUg of
      Pb/g animal/day) the blood ALAD activity inhibition (~82%) remained constant.
      Hematocrit and hemoglobin were significantly reduced only at the highest-doses,
      and the stress indicator, heterophils to lymphocyte (H/L) ratio, did not show
      apparent changes. In a second experiment, house sparrows were exposed to Pb in
      drinking water (12.3 ppm) during either 15 or 30 days. Pb concentration used in
      this study was enough to produce blood lead levels equivalents to those found
      recently in house sparrows inhabiting urban areas, reduced blood ALAD activity
      and inversion of the H/L ratio. Decreasing blood ALAD activities were correlated
      with increasing blood Pb levels. In addition, Pb exposure produced modification
      in the levels of hepatic antioxidant enzymes, increased GST activity and
      decreased CAT activity, without lipid peroxidation. In conclusion, our results
      suggest that blood ALAD activity is a reliable and sensitive biomarker for
      environmental Pb exposure in house sparrows, additionally chronic exposure
      produce physiological stress (H/L inversion) and small changes in antioxidant
      enzyme activity. Finally, this specie could be considered a bioindicator for
      monitoring the urban Pb contamination.

PMID- 29459166
TI  - Acute blockade of inner ear marginal and dark cell K+ secretion: Effects on
      gravity receptor function.
AB  - Specific pharmacological blockade of KCNQ (Kv7) channels with XE991 rapidly
      (within 20 min) and profoundly alters inner ear gravity receptor responses to
      head motion (Lee et al., 2017). We hypothesized that these effects were
      attributable to the suppression of K+ secretion following blockade of KCNQ1-KCNE1
      channels in vestibular dark cells and marginal cells. To test this hypothesis, K+
      secretion was independently inhibited by blocking the Na+-K+-2Cl- cotransporter
      (NKCC1, Slc12a2) rather than KCNQ1-KCNE1 channels. Acute blockade of NKCC1 with
      ethacrynic acid (40 mg/kg) eliminated auditory responses (ABRs) within
      approximately 70 min of injection, but had no effect on vestibular gravity
      receptor function (VsEPs) over a period of 2 h in the same animals. These
      findings show that, vestibular gravity receptors are highly resistant to acute
      disruption of endolymph secretion unlike the auditory system. Based on this we
      argue that acute suppression of K+ secretion alone does not likely account for
      the rapid profound effects of XE991 on gravity receptors. Instead the effects of
      XE991 likely require additional action at KCNQ channels located within the
      sensory epithelium itself.

PMID- 29459167
TI  - Habitat characteristics provide insights of carbon storage in seagrass meadows.
AB  - Seagrass meadows provide multiple ecosystem services, yet they are among the most
      threatened ecosystems on earth. Because of their role as carbon sinks, protection
      and restoration of seagrass meadows contribute to climate change mitigation. Blue
      Carbon strategies aim to enhance CO2 sequestration and avoid greenhouse gasses
      emissions through the management of coastal vegetated ecosystems, including
      seagrass meadows. The implementation of Blue Carbon strategies requires a good
      understanding of the habitat characteristics that influence Corg sequestration.
      Here, we review the existing knowledge on Blue Carbon research in seagrass
      meadows to identify the key habitat characteristics that influence Corg
      sequestration in seagrass meadows, those factors that threaten this function and
      those with unclear effects. We demonstrate that not all seagrass habitats have
      the same potential, identify research priorities and describe the implications of
      the results found for the implementation and development of efficient Blue Carbon
      strategies based on seagrass meadows.

PMID- 29459168
TI  - Predictors of outcomes and refractoriness in status epilepticus: A prospective
      study.

PMID- 29459169
TI  - Update on the management of vasoproliferative tumour.
AB  - CASE REPORT: Here we report a 19-year-old female patient who presented a
      vasoproliferative tumour. It caused complications, such as epiretinal membrane,
      macular oedema, vitreous haemorrhage, and exudative retinal detachment. The
      patient was treated with 3 injections of intravitreal bevacizumab, an
      intravitreal dexamethasone implant, tocilizumab, and double freeze-thaw
      cryotherapy. DISCUSSION: Therapeutic options are: observation, if it is small, if
      it is a peripheral lesion, and if there seems to be no threat to vision. If it
      requires treatment, laser photocoagulation, intravitreal bevacizumab, trans
      conjunctival cryotherapy, transpupillary thermotherapy, photodynamic therapy,
      brachytherapy plaques and surgery are the different options available. Recently,
      tocilizumab and intravitreal dexamethasone implants have been reported to be
      beneficial.

PMID- 29459170
TI  - Treatment of Cervical Spondylotic Amyotrophy With Nerve Transfers.
AB  - Cervical spondylotic amyotrophy is characterized by severe, proximal upper
      extremity weakness including an inability to abduct the shoulder and flex the
      elbow. Treatment using both medical and surgical decompression approaches has
      produced variable results. This paper reports the use of nerve transfers (spinal
      accessory to suprascapular, flexor carpi ulnaris fascicle of ulnar to biceps
      motor branch, radial nerve branch to triceps to axillary) to restore shoulder and
      elbow function in a case of unilateral cervical spondylotic amyotrophy involving
      C5 and C6 myotomes. Evidence of regeneration was observed on electromyography as
      well as clinically at 5 months postoperatively. At 3 years after surgery,
      recovery of elbow flexion and shoulder abduction was Medical Research Council
      grade 4/5 with improved external rotation and considerably improved patient-rated
      Disabilities of the Arm, Shoulder and Hand scores. We propose that nerve
      transfers be considered along with other reconstruction modalities in the
      treatment of cervical spondylotic amyotrophy.

PMID- 29459171
TI  - Tensile and Torsional Structural Properties of the Native Scapholunate Ligament.
AB  - PURPOSE: The ideal material for reconstruction of the scapholunate interosseous
      ligament (SLIL) should replicate the mechanical properties of the native SLIL to
      recreate normal kinematics and prevent posttraumatic arthritis. The purpose of
      our study was to evaluate the cyclic torsional and tensile properties of the
      native SLIL and load to failure tensile properties of the dorsal SLIL. METHODS:
      The SLIL bone complex was resected from 10 fresh-frozen cadavers. The scaphoid
      and lunate were secured in polymethylmethacrylate and mounted on a test machine
      that incorporated an x-y stage and universal joint, which permitted translations
      perpendicular to the rotation/pull axis as well as nonaxial angulations. After a
      1 N preload, specimens underwent cyclic torsional testing (+/-0.45 N m
      flexion/extension at 0.5 Hz) and tensile testing (1-50 N at 1 Hz) for 500 cycles.
      Lastly, the dorsal 10 mm of the SLIL was isolated and displaced at 10 mm/min
      until failure. RESULTS: During intact SLIL cyclic torsional testing, the neutral
      zone was 29.7 degrees  +/- 6.6 degrees  and the range of rotation 46.6 degrees 
      +/- 7.1 degrees . Stiffness in flexion and extension were 0.11 +/- 0.02 and 0.12
      +/- 0.02 N m/deg, respectively. During cyclic tensile testing, the engagement
      length was 0.2 +/- 0.1 mm, the mean stiffness was 276 +/- 67 N/mm, and the range
      of displacement was 0.4 +/- 0.1 mm. The dorsal SLIL displayed a 0.3 +/- 0.2 mm
      engagement length, 240 +/- 65 N/mm stiffness, peak load of 270 +/- 91 N, and
      displacement at peak load of 1.8 +/- 0.3 mm. CONCLUSIONS: We report the torsional
      properties of the SLIL. Our novel test setup allows for free rotation and
      translation, which reduces out-of-plane force application. This may explain our
      observation of greater dorsal SLIL load to failure than previous reports.
      CLINICAL RELEVANCE: By matching the natural ligament with respect to its tensile
      and torsional properties, we believe that reconstructions will better restore the
      natural kinematics of the wrist and lead to improved outcomes. Future clinical
      studies should aim to investigate this further.

PMID- 29459172
TI  - Fracture Risk in Ulnohumeral Arthroplasty-A Biomechanical Study.
AB  - PURPOSE: Ulnohumeral arthroplasty, also known as the Outerbridge-Kashiwagi
      procedure, was popularized after reports of successful results in 1978, and has
      long been a means of management for ulnohumeral arthritis. However, there are
      concerns over the loss of integrity of the distal humerus as a result of
      fenestration. The purpose of this study was to examine the relationship between
      the size of fenestration and fracture risk. METHODS: Using a validated fourth
      generation sawbones model, load to failure and site of fracture were investigated
      following incrementally increasing distal humeral fenestration sizes. Each sample
      was subjected to a uniform extension stress on a materials testing system, with 5
      samples run for each group. The experimental groups began with a fenestration
      size of 10 mm and increased by 3 mm increments up to 31 mm. Load at failure and
      site of fracture were recorded for each sample. RESULTS: Forty-five fourth
      generation sawbones samples were tested. Average load at sample failure was
      equivalent for each fenestration group up to 25 mm. At 28 mm, average load to
      failure began to decrease, and was statistically significant beginning between 28
      mm and 31 mm. At 28 mm, 4 of 5 samples fractured through the fenestration, and at
      31 mm, all 5 samples fractured through the fenestration. This change in fracture
      site became statistically significant between 25 mm and 28 mm. CONCLUSIONS:
      Distal humeral fenestration does compromise its structural integrity; however,
      for resection in the range of 10-25 mm, there is no increased risk of fracture.
      CLINICAL RELEVANCE: On the basis of this biomechanical model, the authors do not
      recommend any activity limitations after initial surgical recovery, but do
      recommend against distal humeral fenestrations larger than 25 mm when performing
      this procedure.

PMID- 29459173
TI  - Acute corrosive poisonings - Frequent cause for fatal outcome.

PMID- 29459174
TI  - EFLDO induces apoptosis in hepatic cancer cells by caspase activation in vitro
      and suppresses tumor growth in vivo.
AB  - To study the apoptosis induced by EFLDO (ent-3alpha-formylabieta-8(14), 13(15)
      dien-16,12beta-olide), extracted from the Euphorbia lunulata Bge, in the HepG2
      cell line and to study the antitumor activity of this compound in vivo, Cell
      viability and migration were evaluated with CCK-8 (2-(2-methoxy-4-nitrophenyl)-3-
      (4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) and wound
      healing assays, respectively. In addition, the cell cycle was examined using flow
      cytometry after propidium iodide (PI) staining. Apoptosis was analyzed by using
      the Annexin V/PI staining assay. Pro-caspase activation and apoptosis protein
      expression were evaluated by western blotting. A HepG2 xenograft model in nude
      mice was also established to study the antitumor activity of EFLDO in vivo.
      Immunohistochemical analysis was used to detect the expression of Ki67 in the
      tumors in situ. EFLDO could induce dose- and time-dependent apoptosis in HepG2
      human hepatic cancer cells. Activation of caspases 3, 8, and 9 played an
      important role in EFLDO-induced apoptosis in vitro. Decreased levels of Bcl-2 and
      Survivin and increased level of BAX were also involved in this process.
      Furthermore, EFLDO could inhibit HepG2 tumor growth in nude mice, and the
      proliferation characteristics, reflected by the Ki67 index, were suppressed
      significantly. The results indicated that EFLDO could induce apoptosis in hepatic
      cancer cells by caspase activation in vitro and suppress tumor growth in vivo.

PMID- 29459175
TI  - [Alveolar hemorrhage and cocaine use].
AB  - In France, cocaine is the second most commonly illicit drug used after cannabis.
      Cocaine, mainly smoked in the form of crack, can be responsible for a wide range
      of respiratory disorders. The aim of this systematic literature review was to
      clarify what is known about the link between cocaine use and alveolar hemorrhage.
      We performed a Medline search covering the period 1980-2016 and collected data
      from 84 articles. The number of acute forms described in the literature is small
      but postmortem studies show that hidden forms are frequent. The diagnosis is
      based on the association of hemoptysis, anemia and diffuse alveolar opacity.
      Bronchoalveolar lavage shows hemosiderin-laden macrophages. Of the 13 cases
      identified, 12 patients had hemoptysis, anemia and diffuse alveolar infiltration
      on pulmonary or chest CT. In 9 cases, the presence of hemosiderin-laden
      macrophages was identified in bronchoalveolar lavage or pulmonary biopsy. Except
      for 2 deaths, the outcome was favorable when cocaine use was stopped. Systematic
      interventions to help people stopping using this psychoactive substance will
      protect lung health.

PMID- 29459176
TI  - Variations of T and B lymphocytes of flounder (Paralichthys olivaceus) after
      Hirame novirhabdovirus infection and immunization.
AB  - T and B lymphocytes are closely related to immunization and pathogen infection.
      Our previous study confirmed the CD3+, CD4-1+, CD4-2+, CD8beta+ T lymphocytes and
      IgM+ B lymphocytes presented in the peripheral blood leukocytes (PBLs) of
      flounder (Paralichthys olivaceus), in this paper, the variations of T and B
      lymphocytes of flounder after Hirame novirhabdovirus (HIRRV) infection or
      immunization were investigated. The flounders were injected with live or
      inactivated HIRRV, then the percentages of T and B lymphocytes in PBLs were
      analyzed by Flow cytometry (FCM), total antibodies and HIRRV-specific antibodies
      in serum were detected by Enzyme-linked immunosorbent assay (ELISA), and
      expression of twelve immune-related genes in the head kidneys were determined
      using q-PCR. The results showed that the percentages of CD3+, CD4-1+, CD4-2+,
      CD8beta+ T lymphocytes and IgM+ B lymphocytes significantly increased in both
      infection and immunization groups, in infection group they decreased rapidly
      after the peak and significantly lower than control levels at the end of
      infection, in immunization group they went down steadily to the control levels at
      the end of immunization. The total antibodies and HIRRV-specific antibodies
      increased first and peaked on the 7th day post infection and on the 14th day post
      immunization, respectively, then gradually decreased to the control levels.
      Additionally, twelve immune-related genes were up-regulated in both groups. These
      results demonstrated that the HIRRV induced both humoral and cellular immunity of
      flounder, the lymphocytes varied more sharply in infection group than those in
      immunization group and CD8+ T lymphocytes responded much more than CD4+ T
      lymphocytes to HIRRV antigen.

PMID- 29459177
TI  - IL-10 correlates with the expression of carboxypeptidase B2 and lymphovascular
      invasion in inflammatory breast cancer: The potential role of tumor infiltrated
      macrophages.
AB  - Pro-carboxypeptidase B2 (pro-CPB2) or thrombin-activatable fibrinolysis inhibitor
      (TAFI) is a glycoprotein encoded by the CPB2 gene and deregulated in several
      cancer types, including breast cancer. Thrombin binding to thrombomodulin (TM),
      encoded by THBD, is important for TAFI activation. CPB2 gene expression is
      influenced by genetic polymorphism and cytokines such as interleukin 10 (IL-10).
      Our previous results showed that tumor infiltrating monocytes/macrophages
      (CD14+/CD16+) isolated from inflammatory breast cancer (IBC) patients' secrete
      high levels of IL-10. The aim of the present study is to test genetic
      polymorphism and expression of CPB2 in healthy breast tissues and carcinoma
      tissues of non-IBC and IBC patients. Furthermore, to investigate whether IL-10
      modulates the expression of CPB2 and THBD in vivo and in-vitro. We tested CPB2
      Thr325Ile polymorphism using restriction fragment length polymorphism, (RFLP)
      technique in healthy and carcinoma breast tissues. The mRNA expression of CPB2,
      THBD and IL10 were assessed by RT-qPCR. Infiltration of CD14+ cells was assessed
      by immunohistochemistry. In addition, we investigated the correlation between
      infiltration of CD14+ cells and expression of IL10 and CPB2. Furthermore, we
      correlated IL10 expression with the expression of both CPB2 and THBD in breast
      carcinoma tissues. Finally, we validated the role of recombinant IL-10 in
      regulating the expression of CPB2 and THBD using different breast cancer cell
      lines. Our results showed that CPB2 genotypes carrying the high-risk allele
      [Thr/Ile (CT) and Ile/Ile (TT)] were more frequent in both IBC and non-IBC
      patients compared to control group. CPB2 genotypes did not show any statistical
      correlation with CPB2 mRNA expression levels or patients' clinical pathological
      properties. Interestingly, CPB2 and IL10 expression were significantly higher and
      positively correlated with the incidence of CD14+ cells in carcinoma tissues of
      IBC as compared to non-IBC. On the other hand, THBD expression was significantly
      lower in IBC carcinoma versus non-IBC tissues. Based on molecular subtypes, CPB2
      and IL10 expression were significantly higher in triple negative (TN) as compared
      to hormonal positive (HP) carcinoma tissues of IBC. Moreover, CPB2 expression was
      positively correlated with presence of lymphovascular invasion and the expression
      of IL10 in carcinoma tissues of IBC patients. Furthermore, recombinant human IL
      10 stimulated CPB2 expression in SUM-149 (IBC cell line) but not in MDA-MB-231
      (non-IBC cell line), while there was no significant effect THBD expression. In
      conclusion, carcinoma tissues of IBC patients are characterized by higher
      expression of CPB2 and lower expression of THBD. Moreover, CPB2 positively
      correlates with IL10 mRNA expression, incidence of CD14+ cells and lymphovascular
      invasion in IBC patients. IL-10 stimulated CPB2 expression in TN-IBC cell line
      suggests a relevant role of CPB2 in the aggressive phenotype of IBC.

PMID- 29459178
TI  - The challenge of treating older patients with pancreaticobiliary malignancies.
AB  - Pancreatic and biliary tract cancers are aggressive malignancies. They commonly
      present with metastatic or unresectable disease. Those that do present with
      resectable cancer have high rates of recurrence. Despite recent advances in
      surgical technique, chemotherapy, and radiotherapy regimens, they are associated
      with poor survival outcomes. These cancers represent an exception to the trend of
      improved overall survival evident in most malignancies in recent decades.
      Depending on the goal of treatment, active management of pancreatic and biliary
      cancers involves surgery, chemotherapy, and radiation therapy, either alone or in
      combination. Both pancreatic and biliary tract cancers have a preponderance in
      the older population. Older patients are a heterogeneous group; although
      tolerability of multimodality treatment may be a challenge for some, many fit
      older patients may be undertreated based on their age alone. The growing field of
      geriatric oncology has highlighted the importance of a comprehensive assessment
      of these patients, and not relying on age alone as a discriminating factor for
      treatment. Management of older patients with pancreaticobiliary cancers is
      particularly challenging owing to limited prospective data in this population. As
      such, there is uncertainty with regard to optimal treatment approaches for these
      patients. In this article, we outline the therapeutic options available to
      patients with localized or advanced pancreatic and biliary tract cancers, and the
      evidence for specified treatment options in the elderly. We examine the inclusion
      and outcomes of elderly patients in relevant clinical trials; the morbidity that
      may be encountered by elderly patients receiving specified treatments and the
      tools that may assist the physician in selecting elderly patients for particular
      treatments.

PMID- 29459179
TI  - NMR analysis of substrate binding to a two-domain chitinase: Comparison between
      soluble and insoluble chitins.
AB  - CJP-4 is a two-domain chitinase from Japanese cedar (Cryptomeria japonica)
      pollen, consisting of an N-terminal CBM18 domain and a GH19 catalytic domain. The
      substrate binding to an inactive mutant protein of full-length CJP-4, in which
      the catalytic acid Glu108 was mutated to glutamine, CJP-4(E108Q), was analyzed by
      NMR spectroscopy. Based on the chemical shift perturbations of 1H-15N HSQC
      signals of Gly26 (CBM18 domain) and Trp185 (GH19 domain), the association
      constants for individual domains of CJP-4(E108Q) toward soluble chitin hexamer
      (GlcNAc)6 were determined to be 2300 and 3500 M-1, respectively. Isothermal
      titration calorimetry provided a similar association constant for (GlcNAc)6 (1980
      M-1) with the one-site binding model. One (GlcNAc)6 molecule appeared to bind to
      a single binding site of CJP-4(E108Q), spanning from CBM18 to GH19 domains. When
      chitin nanofibers, insoluble chitinase substrate, were added to the CJP-4(E108Q)
      solution, strong line-broadening was observed for the majority of the backbone
      resonances in CBM18 domain but not in GH19 domain, indicating a binding
      preference of CBM18 domain to the insoluble chitin. We here demonstrated
      importance of CBM18 domain in insoluble chitin recognition based on the NMR
      binding data obtained for full-length CJP-4. Chitin nanofibers were found to be
      useful for spectroscopic observation of insoluble chitin binding to proteins.

PMID- 29459180
TI  - A new look at acid catalyzed deacetylation of carbohydrates: A regioselective
      synthesis and reactivity of 2-O-acetyl aryl glycopyranosides.
AB  - In the present work we report that acetyl groups of per - acetylated aryl
      glycosides have different reactivity during the acidic deacetylation using
      HCl/EtOH in CHCl3, which leads to preferential deacetylation at O-3, O-4 and O-6.
      Thereby, the one-step preparation of 2-O-acetyl aryl glycosides with simple
      aglycon was accomplished for the first time. It was proved that the found reagent
      is to be general and unique for the preparation of series of 2-O-acetyl aryl
      glycosides. We have determined the influence of both carbohydrate moiety and the
      aglycon on the selectivity of deacetylation reaction by kinetic experiments.
      Using DFT/B3LYP/6-31G(d,p) and semi-empirical AM1 methods we have found that the
      highest activation barrier is for 2-O-acetyl group. This completely explains the
      least reactivity of 2-O-acetyl group.

PMID- 29459181
TI  - Nuclear envelope rupture: little holes, big openings.
AB  - The nuclear envelope (NE), which is a critical barrier between the DNA and the
      cytosol, is capable of extensive dynamic membrane remodeling events in
      interphase. One of these events, interphase NE rupture and repair, can occur in
      both normal and disease states and results in the loss of nucleus
      compartmentalization. NE rupture is not lethal, but new research indicates that
      it could have broad impacts on genome stability and activate innate immune
      responses. These observations suggest a new model for how changes in NE structure
      could be pathogenic in cancer, laminopathies, and autoinflammatory syndromes, and
      redefine the functions of nucleus compartmentalization.

PMID- 29459182
TI  - Understanding epidemiologists who serve as preceptors.
AB  - PURPOSE: This study describes factors associated with epidemiologists from state
      health departments (HDs) who served as preceptors. METHODS: We used the 2014
      Public Health Workforce Interests and Needs Survey, a national survey of state
      health agency workers, and selected those who identify their role in the
      organization as an epidemiologist and a state HD employee for analysis. Variables
      related to recruitment and retention were studied, and predictor variables were
      assessed. We applied statistical analysis of complex sampling design based on
      weights generated by the distribution of the epidemiologists. Logistic regression
      was used to determine factors that are significant predictors of preceptorship.
      RESULTS: Significant factors of increased preceptorship included being black
      (adjusted odds ratios [AOR] = 3.98, 95% confidence interval [CI], 2.01-7.88),
      being a team leader (AOR = 2.09, 95% CI, 1.07-4.05), a supervisor (AOR = 2.75,
      95% CI, 1.25-6.08), or a manager (AOR = 2.70, 95% CI, 1.15-6.34), and
      collaborating with academia (AOR = 3.11, 95% CI, 1.82-5.34). CONCLUSIONS: State
      HDs and academic institutions should collaborate to offer applied epidemiology
      practicum opportunities to (1) increase job satisfaction among applied
      epidemiologists and (2) prepare the incoming workforce to work in applied
      epidemiology.

PMID- 29459184
TI  - Cadmium exposure and cognitive abilities and behavior at 10 years of age: A
      prospective cohort study.
AB  - BACKGROUND: We have previously reported inverse associations of prenatal and
      childhood cadmium exposure with cognition in 5-year-old Bangladeshi children.
      OBJECTIVES: To assess if cadmium exposure affected cognition and behavior in the
      Bangladeshi children at 10 years. METHODS: Cadmium exposure was assessed by
      urinary concentrations at 10 (n = 1498) and 5 years of age (n = 1453), and of the
      mothers in early pregnancy (n = 1299), measured by ICP-MS. Cognitive abilities
      were assessed with Wechsler Intelligence Scale for Children (4th edition) and
      behavior with the parent-rated Strengths and Difficulties Questionnaire. RESULTS:
      In multivariable-adjusted models, urinary cadmium at 10 years was inversely
      associated with Full scale IQ and most of the sub-scales. Associations were
      mainly observed in boys, in whom the difference in Full scale IQ was 7.0 scores
      (95% CI: -11, -2.7), corresponding to 0.21 SD, when comparing those in the
      highest (range: 0.30-2.6 MUg/L) and lowest tertile of urinary cadmium (0.036-0.18
      MUg/L). Urinary cadmium at 5 years was inversely, but not significantly,
      associated with IQ. Children in the highest exposure tertile at 10 years also had
      poorer Prosocial behavior scores. The association appeared strongest in girls, in
      whom the corresponding OR for Prosocial scores in relation to cadmium exposure at
      10 years and prenatally was 0.58 (95% CI: 0.34, 0.99) and 0.48 (95% CI: 0.25,
      0.93), respectively. CONCLUSION: Childhood cadmium exposure was associated with
      lower intelligence in boys, and there were indications of altered behavior in
      girls for both prenatal and childhood exposures. Findings are of concern as
      similar exposure levels are common world-wide.

PMID- 29459183
TI  - Transcriptional differences between smokers and non-smokers and variance by
      obesity as a risk factor for human sensitivity to environmental exposures.
AB  - BACKGROUND: Obesity has been shown to alter response to air pollution and smoking
      but underlying biological mechanisms are largely unknown and few studies have
      explored mechanisms by which obesity increases human sensitivity to environmental
      exposures. OBJECTIVE: Overall study goals were to investigate whole blood gene
      expression in smokers and non-smokers to examine associations between cigarette
      smoke and changes in gene expression by obesity status and test for effect
      modification. METHODS: Relative fold-change in mRNA expression levels of 84 genes
      were analyzed using a Toxicity and Stress PCR array among 50 21-54 year old
      adults. Data on smoking status was confirmed using urinary cotinine levels.
      Adjusted models included age, gender, white blood cell count and body-mass index.
      RESULTS: Models comparing gene expression of smokers vs. non-smokers identified
      six differentially expressed genes associated with smoking after adjustments for
      covariates. Obesity was associated with 29 genes differentially expressed
      compared to non-obese. We also identified 9 genes with significant
      smoking/obesity interactions influencing mRNA levels in adjusted models comparing
      expression between smokers vs non-smokers for four DNA damage related genes
      (GADD45A, DDB2, RAD51 and P53), two oxidative stress genes (FTH1, TXN), two
      hypoxia response genes (BN1P3lL, ARNT), and one gene associated with unfolded
      protein response (ATF6B). CONCLUSIONS: Findings suggest that obesity alters human
      sensitivity to smoke exposures through several biological pathways by modifying
      gene expression. Additional studies are needed to fully understand the clinical
      impact of these effects, but risk assessments should consider underlying
      phenotypes, such as obesity, that may modulate sensitivity of vulnerable
      populations to environmental exposures.

PMID- 29459185
TI  - FAMI Screws for Mandibulo-Maxillary fixation in mandibular fracture treatment -
      Clinico-radiological evaluation.
AB  - Mandibulo-maxillary fixation (MMF) is indispensable for mandibular fracture
      treatment. Various means for MMF have been proposed, of which arch bars are
      widely considered to be the mainstay. However, disadvantages to this method have
      initiated a quest for an alternative, leading to the introduction of MMF screws.
      MMF screws have frequently been criticized for poor stability of fracture sites,
      root damage, hardware failure, and nerve damage. We retrospectively evaluate the
      FAMI (Fixation and Adaptation in Mandibular Injuries) screw in mandibular
      fracture treatment by scanning for clinically and radiologically visible
      complications. In total, 534 FAMI screws were used in the successful treatment of
      96 males and 34 females. Condylar fractures were most commonly encountered,
      representing 120 of 241 fracture sites. 15 general fracture-related complications
      occurred, with the most common being nerve function impairment (3.8%) and
      postoperative malocclusion (4.6%). In nine cases (7%), clinically visible FAMI
      screw-related complications occurred, with the most prevalent being screw
      loosening (2.3%) and mucosal signs of inflammation (3.1%). Duration of FAMI
      screws was associated with the occurrence of clinically visible complications (p
      = 0.042). Radiologically, clinically invisible dental hard tissue damage was
      noted in 21 individuals (16%). Therefore, FAMI screws seem to be a reliable and
      safe method for mandibulo-maxillary fixation.

PMID- 29459186
TI  - Squamous cell carcinoma of the maxilla: Analysis of clinicopathological
      predictors for disease recurrence and metastatic behavior.
AB  - INTRODUCTION: Squamous cell carcinoma of the maxilla only constitutes a small
      fraction of Head and Neck Cancers. There is thereby a lack of information about
      frequent tumor staging and localization and their effect on patients' outcome.
      The main factors that influence longterm survival in HNSCC are the extent of the
      primary disease and recurrence rate, including local neck metastases. PATIENTS
      AND METHODS: In this study, clinical outcome and rates of disease recurrence in
      68 surgically treated patients with maxillary SCC were evaluated in terms of
      primary tumor staging and localization. RESULTS: It could be demonstrated that
      maxillary cancer is mostly located in the posterior region of the upper jaw
      (70%). The rate of neck node metastasis was 35.3%, which is equivalent to the
      rest of the oral cavity and supports the role of elective neck dissection for
      patients with clinically negative neck node status. Staging, tumor
      differentiation, and infiltration of lymphatic structures correlated
      significantly with the development of local neck node metastases (r = 0.321, p =
      0.01; r = 0.348, p < 0.01; r = 0.64; p < 0.01). CONCLUSION: Maxillary carcinomas
      exhibit similar rates of locoregional disease recurrence as the rest of the oral
      cavity. The existence of cervical metastases even in patients with T1 tumors
      supports the concept of elective neck dissection in early tumors with clinically
      negative neck status.

PMID- 29459187
TI  - Association between third molar and mandibular angle fracture: A systematic
      review and meta-analysis.
AB  - PURPOSE: The aim of this study was to investigate the risk of mandibular angle
      fracture associated with the presence of a mandibular third molar and its
      position when the mandibular fracture occurs. METHODS: A systematic literary
      search was performed in Pubmed, Scopus, and the Cochrane Library for
      observational studies with at least 250 patients that included frequency of
      mandibular angle fracture, presence of third molar, and its position. RESULTS: A
      total of seven studies were included in the review, from an initial search of 622
      titles. The relative risk of mandibular angle fracture with third molar was 1.90
      (95% CI = 1.47-2.46). The relative risk of mandibular angle fracture related to
      third molar position (according to the Pell and Gregory classification) was 1.18
      (95% CI = 0.62-2.25), 1.98 (95% CI = 0.95-4.10), 2.72 (95% CI = 1.78-4.16), 1.31
      (95% CI = 0.80-2.14), 2.21 (95% CI = 1.69-2.87) and 2.99 (95% CI = 2.12-4.22) for
      Class A, Class B, Class C, Class I, Class II, and Class III, respectively.
      CONCLUSIONS: Our meta-analysis reported a two-fold increased risk of mandibular
      angle fracture with the presence of a third molar in patients who presented with
      mandibular fractures. Even the third molar position seemed to influence
      mandibular angle fracture, especially Class C, Class II, and Class III.

PMID- 29459189
TI  - Detailed investigations into the Akabori-Momotani reaction for the synthesis of
      amphetamine type stimulants: Part 2.
AB  - The Akabori-Momotani reaction can be used to synthesise pseudoephedrine in 50%
      yield from N-methylalanine and benzaldehyde. This paper investigates electronic
      effects of substituted benzaldehydes on the reaction to synthesise amphetamine
      type stimulants and identifies several new Akabori-Momotani by-products, 1-[(4
      methoxybenzyl)(methyl)amino]ethanol (11c), 2-(4-methoxyphenyl)-3,4-dimethyl-1,3
      oxazolidine (12c), 1,2,3,4-tetramethyl-5,6-di-(4-methoxyphenyl)piperazine (13c)
      and 1,2,4,5-tetramethyl-3,6-di-(4-methoxyphenyl)piperazine (14c). This paper also
      investigates pseudoephedrine and methamphetamine isomeric distribution from the
      Akabori-Momotani reaction with the aid of molecular modelling to understand why
      more pseudoephedrine than ephedrine is produced.

PMID- 29459188
TI  - Acupuncture for the treatment of post-partum urinary retention.
AB  - STUDY OBJECTIVES: The aims of the present study were to evaluate acupuncture as
      an alternative treatment to an indwelling catheter for women with postpartum
      urinary retention, and to evaluate the accuracy of sonographic estimation of
      bladder volume by portable bedside equipment in women postpartum. STUDY
      BACKGROUND: Post-partum urinary retention is a common obstetric complication. The
      accepted method for diagnosing post void residual bladder volume is by ultrasound
      or catheterization. However, the accuracy of bedside sonographic evaluation of
      bladder volume in women postpartum is controversial due to anatomical and
      technical issues. The traditional treatment of urinary retention is
      catheterization for variable lengths of time. Acupuncture, while an accepted
      treatment method for urinary retention in traditional societies in the Far East,
      has not been proven scientifically to resolve the problem. Therefore, the aims of
      our study were to evaluate acupuncture as an alternative treatment to
      catheterization for urinary retention, and to evaluate the accuracy of
      sonographic estimation of bladder volume by portable bedside ultrasound in women
      postpartum. MATERIALS AND METHODS: The study was a prospective randomized case
      controlled trial conducted in 55 women post-partum with urinary retention. All
      patients underwent a pre and post treatment sonographic evaluation of bladder
      volume. Women with urinary retention were given the choice of treatment by
      acupuncture or catheterization. Acupuncture was performed by an experienced
      acupuncturist licensed in Traditional Chinese Medicine and point selection was
      based on Meridian theory and clinical experience. RESULTS: In the acupuncture
      group, 23 women (92%) achieved spontaneous micturition within one hour following
      treatment. Bedside sonographic evaluation of bladder volume showed excellent
      correlation to actual volume as measured by catheterization (r2 = 0.988).
      CONCLUSION: Acupuncture proved to be an excellent alternative to catheterization
      in treatment of women with postpartum urinary retention.

PMID- 29459190
TI  - The Koukopoulos Mixed Depression Rating Scale (KMDRS): An International Mood
      Network (IMN) validation study of a new mixed mood rating scale.
AB  - BACKGROUND: It has been proposed that the broad major depressive disorder (MDD)
      construct is heterogenous. Koukopoulos has provided diagnostic criteria for an
      important subtype within that construct, "mixed depression" (MxD), which
      encompasses clinical pictures characterized by marked psychomotor or inner
      excitation and rage/anger, along with severe depression. This study provides
      psychometric validation for the first rating scale specifically designed to
      assess MxD symptoms cross-sectionally, the Koukopoulos Mixed Depression Rating
      Scale (KMDRS). METHODS: 350 patients from the international mood network (IMN)
      completed three rating scales: the KMDRS, Montgomery-Asberg Depression Rating
      Scale (MADRS) and Young Mania Rating Scale (YMRS). KMDRS' psychometric properties
      assessed included Cronbach's alpha, inter-rater reliability, factor analysis,
      predictive validity, and Receiver Operator Curve analysis. RESULTS: Internal
      consistency (Cronbach's alpha = 0.76; 95% CI 0.57, 0.94) and interrater
      reliability (kappa = 0.73) were adequate. Confirmatory factor analysis identified
      2 components: anger and psychomotor excitation (80% of total variance). Good
      predictive validity was seen (C-statistic = 0.82 95% CI 0.68, 0.93). Severity cut
      off scores identified were as follows: none (0-4), possible (5-9), mild (10-15),
      moderate (16-20) and severe (> 21) MxD. LIMITATIONS: Non DSM-based diagnosis of
      MxD may pose some difficulties in the initial use and interpretation of the
      scoring of the scale. Moreover, the cross-sectional nature of the evaluation does
      not verify the long-term stability of the scale. CONCLUSIONS: KMDRS was a
      reliable and valid instrument to assess MxD symptoms.

PMID- 29459191
TI  - A review of the curriculum development process of simulation-based educational
      intervention studies in Korea.
AB  - BACKGROUND: Despite the increase in simulators at nursing schools and the high
      expectations regarding simulation for nursing education, the unique features of
      integrating simulation-based education into the curriculum are unclear.
      OBJECTIVE: The purpose of this study was to assess the curriculum development
      process of simulation-based educational interventions in nursing in Korea.
      DESIGN: Integrative review of literature used. DATA SOURCES: Korean Studies
      Information Services System (KISS), Korean Medical Database (KMbase), KoreaMed,
      Research Information Sharing Service (RISS), and National Digital Library (NDL).
      METHODS: Comprehensive databases were searched for records without a time limit
      (until December 2016), using terms such as "nursing," "simulation," and
      "education." A total of 1006 studies were screened. According to the model for
      simulation-based curriculum development (Khamis et al., 2016), the quality of
      reporting on the curriculum development was reviewed. RESULTS: A total of 125
      papers were included in this review. In three studies, simulation scenarios were
      made from easy to difficulty levels, and none of the studies presented the level
      of learners' proficiency. Only 17.6% of the studies reported faculty development
      or preparation. The inter-rater reliability was presented in performance test by
      24 studies and two studies evaluated the long-term effects of simulation
      education although there was no statistically significant change in terms of
      publication years. CONCLUSION: These findings suggest that educators and
      researchers should pay more attention to the educational strategies to integrate
      simulation into nursing education. It could contribute to guiding educators and
      researchers to develop a simulation-based curriculum and improve the quality of
      nursing education research.

PMID- 29459192
TI  - Investigating the impact of moulage on simulation engagement - A systematic
      review.
AB  - BACKGROUND: Simulation Based Education (SBE) is used as a primer for clinical
      education in nursing and other health professions. Participant engagement
      strategies and good debriefing have been identified as key for effective
      simulations. The environment in which the simulation is situated also plays a
      large role in the degree of participant engagement. Various cues are staged
      within simulations to enhance this engagement process. Moulage techniques are
      used in current-day simulation to mimic illnesses and wounds, acting as visual
      and tactile cues for the learner. To effectively utilise moulage in simulation,
      significant expense is required to train simulation staff and to purchase
      relevant equipment. OBJECTIVE: Explore the use of moulage in simulation practice
      today and its influence on participant engagement. DESIGN: Using a systematic
      process to extract papers, we reviewed the literature with a critical-realist
      lens. DATA SOURCES: CINAHL Complete, ERIC, Embase, Medline, PsycINFO, SCOPUS, Web
      of Science, Proquest, Science Direct and SAGE. REVIEW METHODS: 10 databases were
      systematically reviewed using the keyword "moulage" to answer the question "How
      does the authenticity of moulage impact on participant engagement?". 1318 records
      were identified prior to exclusion criterion were applied. 10 articles were
      targeted for review, following exclusion for English language and publication
      between 2005 and 2015. RESULTS: The resulting 10 papers were assessed for quality
      using the Medical Education Research Study Quality Instrument (MERSQI). The
      majority of papers were situated in dermatology teaching, with only one nursing
      paper. Study participants were both undergraduate and postgraduate. Most of the
      studies were undertaken at a university setting. No papers comprehensively
      addressed whether the authenticity of moulage influences learner engagement.
      CONCLUSIONS: Results were limited, yet clearly outline a widely held assumption
      that moulage is essential in simulation-based education for improved realism and
      subsequent learner engagement. Despite this, there is no clear evidence from the
      literature that this is the case, suggesting that further research to explore the
      impact of moulage on participant engagement is warranted. A number of
      recommendations are made for future research.

PMID- 29459193
TI  - Personal domains assessed in multiple mini interviews (MMIs) for healthcare
      student selection: A narrative synthesis systematic review.
AB  - OBJECTIVES: To examine the personal domains multiple mini interviews (MMIs) are
      being designed to assess, explore how they were determined and contextualise such
      domains in current and future healthcare student selection processes DESIGN: A
      systematic review of empirical research reporting on MMI model design was
      conducted from database inception to November 2017. DATA SOURCES: Twelve
      electronic bibliographic databases. REVIEW METHODS: Evidence was extracted from
      original studies, and integrated in a narrative synthesis guided by the PRISMA
      statement for reporting systematic reviews. Personal domains were clustered into
      themes using a modified Delphi technique. RESULTS: A total of 584 articles were
      screened. 65 unique studies (80 articles) matched our inclusion criteria of which
      seven were conducted within nursing/midwifery faculties. Six in 10 studies
      featured applicants to medical school. Across selection processes, we identified
      32 personal domains assessed by MMIs, the most frequent being: communication
      skills (84%), teamwork/collaboration (70%), and ethical/moral judgement (65%).
      Domains capturing ability to cope with stressful situations (14%), make decisions
      (14%), and resolve conflict in the workplace (13%) featured in fewer than ten
      studies overall. Intra- and inter-disciplinary inconsistencies in domain profiles
      were noted, as well as differences by entry level. MMIs deployed in nursing and
      midwifery assessed compassion and decision-making more frequently than in all
      other disciplines. Own programme philosophy and professional body guidance were
      most frequently cited (~50%) as sources for personal domains; a blueprinting
      process was reported in only 8% of studies. CONCLUSIONS: Nursing, midwifery and
      allied healthcare professionals should develop their theoretical frameworks for
      MMIs to ensure they are evidence-based and fit-for-purpose. We suggest a re
      evaluation of domain priorities to ensure that students who are selected, not
      only have the capacity to offer the highest standards of care provision, but are
      able to maintain these standards when facing clinical practice and organisational
      pressures.

PMID- 29459194
TI  - The value of psychosocial group activity in nursing education: A qualitative
      analysis.
AB  - BACKGROUND: Nursing faculty often struggle to find effective teaching strategies
      for nursing students that integrate group work into nursing students' learning
      activities. OBJECTIVES: This study was conducted to evaluate students'
      experiences in a psychiatric and mental health nursing course using psychosocial
      group activities to develop therapeutic communication and interpersonal
      relationship skills, as well as to introduce psychosocial nursing interventions.
      METHODS: A qualitative research design was used. The study explored nursing
      students' experiences of the course in accordance with the inductive,
      interpretative, and constructive approaches via focus group interviews.
      Participants were 17 undergraduate nursing students who registered for a
      psychiatric and mental health nursing course. The collected data were analyzed by
      qualitative content analysis. RESULTS: The analysis resulted in 28 codes, 14
      interpretive codes, 4 themes (developing interpersonal relationships, learning
      problem-solving skills, practicing cooperation and altruism, and getting insight
      and healing), and a core theme (interdependent growth in self-confidence).
      CONCLUSIONS: The psychosocial group activity provided constructive opportunities
      for the students to work independently and interdependently as healthcare team
      members through reflective learning experiences.

PMID- 29459195
TI  - Cultural adaptation and validation of the Lasater Clinical Judgment Rubric in
      nursing students in Spain.
AB  - BACKGROUND: The clinical judgment and decision-making abilities of nurses can
      influence many health outcomes, hence the importance of addressing these
      qualities in university studies. In this respect, clinical simulation is a
      commonly employed teaching method. The evaluation of simulation activities
      requires standardised instruments, such as the Lasater Clinical Judgment Rubric,
      which is widely used for this purpose, although a culturally adapted and
      validated version in Spain is not available. AIMS: To obtain a Spanish culturally
      adapted and validated version of the rubric for undergraduate students of
      nursing. DESIGN, PARTICIPANTS AND SETTING: Cultural adaptation and psychometric
      validation study carried out with undergraduate nursing students in the
      simulation laboratories at the University of Malaga (Spain). METHODS: A process
      of translation/back-translation and cultural adaptation was carried out in
      accordance with international standards. The rubric was empirically evaluated in
      standardised scenarios with high and medium-fidelity simulators. Each student
      took part in two different simulation sessions, led by two instructors. In each
      simulation, the data were collected by two independent observers. RESULTS: 152
      observations were obtained from 76 students. The interobserver reliability was
      high, with an intraclass correlation coefficient of 0.93 (95% CI 0.92-0.95) (p =
      0.0001) and Cronbach's alpha of 0.93. According to the confirmatory factor
      analysis, the fit of the model was satisfactory in all indices, with a chi2/df
      value of 1.08, GFI 0.96, TLI 0.99, NFI 0.97 and RMSEA 0.24 (90% CI 0.000-0.066).
      CONCLUSIONS: The rubric obtained is culturally adapted to the Spanish educational
      context, and is valid and reliable for nursing students. Further prospective
      studies should be undertaken to evaluate the responsiveness, potential for
      transfer to clinical practice and cost-benefit ratios of different simulation
      designs.

PMID- 29459196
TI  - A Student Assessment Tool for Standardized Patient Simulations (SAT-SPS):
      Psychometric analysis.
AB  - BACKGROUND: The evaluation of the level of clinical competence acquired by the
      student is a complex process that must meet various requirements to ensure its
      quality. The psychometric analysis of the data collected by the assessment tools
      used is a fundamental aspect to guarantee the student's competence level. AIM: To
      conduct a psychometric analysis of an instrument which assesses clinical
      competence in nursing students at simulation stations with standardized patients
      in OSCE-format tests. METHOD: The construct of clinical competence was
      operationalized as a set of observable and measurable behaviors, measured by the
      newly-created Student Assessment Tool for Standardized Patient Simulations (SAT
      SPS), which was comprised of 27 items. The categories assigned to the items were
      'incorrect or not performed' (0), 'acceptable' (1), and 'correct' (2).
      PARTICIPANTS: 499 nursing students. Data were collected by two independent
      observers during the assessment of the students' performance at a four-station
      OSCE with standardized patients. Descriptive statistics were used to summarize
      the variables. The difficulty levels and floor and ceiling effects were
      determined for each item. Reliability was analyzed using internal consistency and
      inter-observer reliability. The validity analysis was performed considering face
      validity, content and construct validity (through exploratory factor analysis),
      and criterion validity. RESULTS: Internal reliability and inter-observer
      reliability were higher than 0.80. The construct validity analysis suggested a
      three-factor model accounting for 37.1% of the variance. These three factors were
      named 'Nursing process', 'Communication skills', and 'Safe practice'. A
      significant correlation was found between the scores obtained and the students'
      grades in general, as well as with the grades obtained in subjects with clinical
      content. CONCLUSIONS: The assessment tool has proven to be sufficiently reliable
      and valid for the assessment of the clinical competence of nursing students using
      standardized patients. This tool has three main components: the nursing process,
      communication skills, and safety management.

PMID- 29459197
TI  - Student perception of initial transition into a nursing program: A mixed methods
      research study.
AB  - BACKGROUND: Transition into undergraduate education programs is stressful and
      impacts students' well-being and academic achievement. Previous research
      indicates nursing students experience stress, depression, anxiety, and poor
      lifestyle habits which interfere with learning. However, nursing students'
      experience of transition into nursing programs has not been well studied.
      Incongruence exists between this lack of research and the desire to foster
      student success. OBJECTIVES: This study analyzed students' experiences of initial
      transition into a nursing program. DESIGN: An embedded mixed method design.
      SETTING: A single site of a direct-entry, four year baccalaureate Canadian
      nursing program. PARTICIPANTS: All first year nursing students enrolled in the
      fall term of 2016. METHODS: This study combined the Student Adaptation to College
      Questionnaire (SACQ) with a subset of participants participating in qualitative
      focus groups. Quantitative data was analyzed using descriptive statistics to
      identify statistically significant differences in full-scale and subscale scores.
      Qualitative data was analyzed utilizing thematic analysis. RESULTS: Significant
      differences were seen between those who moved to attend university and those who
      did not, with those who moved scoring lower on the Academic Adjustment subscale.
      Focus group thematic analysis highlighted how students experienced initial
      transition into a baccalaureate nursing program. Identified themes included
      reframing supports, splitting focus/finding focus, negotiating own expectations,
      negotiating others' expectations, and forming identity. These findings form the
      Undergraduate Nursing Initial Transition (UNIT) Framework. CONCLUSION:
      Significance of this research includes applications in faculty development and
      program supports to increase student success in the first year of nursing and to
      provide foundational success for ongoing nursing practice.

PMID- 29459198
TI  - The educational impact of web-based and face-to-face patient deterioration
      simulation programs: An interventional trial.
AB  - BACKGROUND: There are international concerns relating to the management of
      patient deterioration. The "failure to rescue" literature identifies that nursing
      staff miss cues of deterioration and often fail to call for assistance.
      Simulation-based educational approaches may improve nurses' recognition and
      management of patient deterioration. OBJECTIVES: To investigate the educational
      impact of the First2Act web-based (WB) and face-to-face (F2F) simulation
      programs. DESIGN & SETTING: A mixed methods interventional cohort trial with
      nursing staff from four Australian hospitals. PARTICIPANTS: Nursing staff working
      in four public and private hospital medical wards in the State of Victoria.
      METHODS: In 2016, ward nursing staff (n = 74) from a public and private hospital
      completed three F2F laboratory-based team simulations with a patient actor in
      teams of three. 56 nursing staff from another public and private hospital
      individually completed a three-scenario WB simulation program (First2ActWeb) [A
      91% participation rate]. Validated tools were used to measure knowledge (multi
      choice questionnaire), competence (check-list of actions) and confidence (self
      rated) before and after the intervention. RESULTS: Both WB and F2F participants'
      knowledge, competence and confidence increased significantly after training (p
      <=0.001). Skill performance for the WB group increased significantly from 61% to
      74% (p <= 0.05) and correlated significantly with post-test knowledge (p =
      0.014). No change was seen in the F2F groups' performance scores. Course
      evaluations were positive with median ratings of 4/5 (WB) and 5/5 (F2F). The F2F
      program received significantly more positive evaluations than the WB program (p <
      0.05), particularly with regard to quality of feedback. CONCLUSION: WB and F2F
      simulation are effective education strategies with both programs demonstrating
      positive learning outcomes. WB programs increase ease of access to training
      whilst F2F enable the development of tactile hands on skills and teamwork. A
      combined blended learning education strategy is recommended to enhance competence
      and patient safety.

PMID- 29459199
TI  - Nursing students experienced personal inadequacy, vulnerability and
      transformation during their patient care encounter: A qualitative meta-synthesis.
AB  - OBJECTIVES: To identify, appraise and synthesize the best available evidence
      exploring nursing students' experiences of professional patient care encounters
      in a hospital unit. DESIGN: The Joanna Briggs Institute (JBI) guidelines were
      followed and a meta-synthesis was conducted. DATA SOURCES: Qualitative research
      articles were considered for inclusion in the review, and JBI's meta-aggregative
      approach to synthesizing qualitative evidence was followed. An extensive search
      for relevant literature was undertaken in scientific databases. REVIEW METHODS:
      Data were extracted from the included research articles, and qualitative research
      findings were pooled using the Qualitative Assessment and Review Instrument. This
      involved categorization of findings on the basis of similarity of meaning and
      aggregation of these categories to produce a comprehensive set of synthesized
      findings. RESULTS: A total of five research articles met the inclusion criteria
      and were included in the review. The review process resulted in 46 subcategories
      that were aggregated into 13 categories. The categories generated four
      synthesized findings: personal existence; personal learning and development;
      being a professional fellow human; and clinical learning environment.
      CONCLUSIONS: We meta-synthesized that: Nursing students experienced personal
      inadequacy, vulnerability and a transformation during their patient care
      encounter.

PMID- 29459200
TI  - Perceived vulnerability moderates the relations between the use of protective
      behavioral strategies and alcohol use and consequences among high-risk young
      adults.
AB  - Drinking protective behavioral strategies (PBS) have been associated with
      reductions in alcohol use and alcohol-related consequences in young adults. PBS
      subscales, Limiting/Stopping (LS), Manner of Drinking (MOD), and Serious Harm
      Reduction (SHR), have been examined in the literature; LS, MOD, and SHR have
      mixed support as protective factors. Understanding moderators between PBS and
      alcohol use and related consequences is an important development in PBS research
      in order to delineate when and for whom PBS use is effective in reducing harm
      from alcohol use. Perceptions of vulnerability to negative consequences, included
      in health-risk models, may be one such moderator. The current study examined
      whether two types of perceived vulnerability (perceived vulnerability when
      drinking; perceived vulnerability in uncomfortable/unfamiliar situations)
      moderated the relations between LS, MOD, SHR strategies and alcohol use and
      related negative consequences. High-risk young adults (N = 400; 53.75% female)
      recruited nationally completed measures of PBS, alcohol use and related
      consequences, and measures of perceived vulnerability. Findings demonstrated that
      perceived vulnerability when drinking moderated the relations between MOD
      strategies and alcohol use. The interactions between perceived vulnerability when
      drinking and PBS did not predict alcohol-related consequences. Perceived
      vulnerability in unfamiliar/uncomfortable social situations moderated relations
      between MOD strategies and both alcohol use and related negative consequences; no
      other significant interactions emerged. Across both perceived vulnerability types
      and MOD strategies, those with the highest levels of perceived vulnerability and
      who used MOD strategies the most had the greatest decrements in alcohol use and
      related negative consequences. Prevention and intervention implications are
      discussed.

PMID- 29459201
TI  - Problematic internet use as an age-related multifaceted problem: Evidence from a
      two-site survey.
AB  - BACKGROUND AND AIMS: Problematic internet use (PIU; otherwise known as Internet
      Addiction) is a growing problem in modern societies. There is scarce knowledge of
      the demographic variables and specific internet activities associated with PIU
      and a limited understanding of how PIU should be conceptualized. Our aim was to
      identify specific internet activities associated with PIU and explore the
      moderating role of age and gender in those associations. METHODS: We recruited
      1749 participants aged 18 and above via media advertisements in an Internet-based
      survey at two sites, one in the US, and one in South Africa; we utilized Lasso
      regression for the analysis. RESULTS: Specific internet activities were
      associated with higher problematic internet use scores, including general surfing
      (lasso beta: 2.1), internet gaming (beta: 0.6), online shopping (beta: 1.4), use
      of online auction websites (beta: 0.027), social networking (beta: 0.46) and use
      of online pornography (beta: 1.0). Age moderated the relationship between PIU and
      role-playing-games (beta: 0.33), online gambling (beta: 0.15), use of auction
      websites (beta: 0.35) and streaming media (beta: 0.35), with older age associated
      with higher levels of PIU. There was inconclusive evidence for gender and gender
      * internet activities being associated with problematic internet use scores.
      Attention-deficit hyperactivity disorder (ADHD) and social anxiety disorder were
      associated with high PIU scores in young participants (age <= 25, beta: 0.35 and
      0.65 respectively), whereas generalized anxiety disorder (GAD) and obsessive
      compulsive disorder (OCD) were associated with high PIU scores in the older
      participants (age > 55, beta: 6.4 and 4.3 respectively). CONCLUSIONS: Many types
      of online behavior (e.g. shopping, pornography, general surfing) bear a stronger
      relationship with maladaptive use of the internet than gaming supporting the
      diagnostic classification of problematic internet use as a multifaceted disorder.
      Furthermore, internet activities and psychiatric diagnoses associated with
      problematic internet use vary with age, with public health implications.

PMID- 29459203
TI  - Comprehensive evaluation on effective leaching of critical metals from spent
      lithium-ion batteries.
AB  - Recovery of metals from spent lithium-ion batteries (LIBs) has attracted
      worldwide attention because of issues from both environmental impacts and
      resource supply. Leaching, for instance using an acidic solution, is a critical
      step for effective recovery of metals from spent LIBs. To achieve both high
      leaching efficiency and selectivity of the targeted metals, improved
      understanding on the interactive features of the materials and leaching solutions
      is highly required. However, such understanding is still limited at least caused
      by the variation on physiochemical properties of different leaching solutions. In
      this research, a comprehensive investigation and evaluation on the leaching
      process using acidic solutions to recycle spent LIBs is carried out. Through
      analyzing two important parameters, i.e. leaching speed and recovery rate of the
      corresponding metals, the effects of hydrogen ion concentration, acid species and
      concentration on these two parameters were evaluated. It was found that a
      leachant with organic acids may leach Co and Li from the cathode scrap and leave
      Al foil as metallic form with high leaching selectivity, while that with
      inorganic acids typically leach all metals into the solution. Inconsistency
      between the leaching selectivity and efficiency during spent LIBs recycling is
      frequently noticed. In order to achieve an optimal status with both high leaching
      selectivity and efficiency (especially at high solid-to-liquid ratios), it is
      important to manipulate the average leaching speed and recovery rate of metals to
      optimize the leaching conditions. Subsequently, it is found that the leaching
      speed is significantly dependent on the hydrogen ion concentration and the
      capability of releasing hydrogen ions of the acidic leachant during leaching.
      With this research, it is expected to improve understanding on controlling the
      physiochemical properties of a leaching solution and to potentially design
      processes for spent LIBs recycling with high industrial viability.

PMID- 29459202
TI  - Inhibition of non-homologous end joining in Fanconi Anemia cells results in
      rescue of survival after interstrand crosslinks but sensitization to replication
      associated double-strand breaks.
AB  - When Fanconi Anemia (FA) proteins were depleted in human U2OS cells with
      integrated DNA repair reporters, we observed decreases in homologous
      recombination (HR), decreases in mutagenic non-homologous end joining (m-NHEJ)
      and increases in canonical NHEJ, which was independently confirmed by measuring
      V(D)J recombination. Furthermore, depletion of FA proteins resulted in reduced HR
      protein foci and increased NHEJ protein recruitment to replication-associated
      DSBs, consistent with our observation that the use of canonical NHEJ increases
      after depletion of FA proteins in cycling cells. FA-depleted cells and FA-mutant
      cells were exquisitely sensitive to a DNA-PKcs inhibitor (DNA-PKi) after
      sustaining replication-associated double strand breaks (DSBs). By contrast, after
      DNA interstrand crosslinks, DNA-PKi resulted in increased survival in FA
      deficient cells, implying that NHEJ is contributing to lethality after crosslink
      repair. Our results suggest FA proteins inhibit NHEJ, since repair intermediates
      from crosslinks are rendered lethal by NHEJ. The implication is that bone marrow
      failure in FA could be triggered by naturally occurring DNA crosslinks, and DNA
      PK inhibitors would be protective. Since some sporadic cancers have been shown to
      have deficiencies in the FA-pathway, these tumors should be vulnerable to NHEJ
      inhibitors with replication stress, but not with crosslinking agents, which could
      be tested in future clinical trials.

PMID- 29459204
TI  - The anaerobic digestion of pig carcase with or without sugar beet pulp, as a
      novel on-farm disposal method.
AB  - Anaerobic digestion was investigated as a potential method for on-farm disposal
      of fallen stock (pig carcases), degrading the carcase material to produce biogas
      and digestate. The effects of feedstock (sugar beet pulp or pig carcase material
      or a 50:50 mix) and organic loading rate (50 g-TS L-1 or 100 g-TS L-1), during
      mesophilic (35  degrees C) anaerobic digestion were investigated. Anaerobic
      digestion was achieved for all experimental treatments, however the pig carcase
      material at the higher organic loading rate produced the second highest methane
      yield (0.56 Nm3 kg-VS-1 versus a range of 0.14-0.58 Nm3 kg-VS-1 for other
      treatments), with the highest percentage of methane in total biogas (61.6% versus
      a range of 36.1-55.2% for all other treatments). Satisfactory pathogen reduction
      is a legislative requirement for disposal of carcase material. Pathogens were
      quantified throughout the anaerobic digestion process. Enterococcus faecalis
      concentrations decreased to negligible levels (2.8 log10 CFU g-TS-1), whilst
      Clostridium perfringens levels remained unaffected by treatment throughout the
      digestion process (5.3 +/- 0.2 log10 CFU g-TS-1).

PMID- 29459205
TI  - Environmental monitoring of a landfill area through the application of carbon
      stable isotopes, chemical parameters and multivariate analysis.
AB  - Leachate produced during an organic matter decomposition process has a complex
      composition and can cause contamination of surface and groundwaters adjacent to a
      landfill area. The monitoring of these areas is extremely important for the
      characterization of the leachate produced and to avoid or mitigate environmental
      damages. Thus, the present study has the objective of monitoring the area of a
      Brazilian landfill using conventional parameters (dissolved metals and anions in
      water) and alternative, stable carbon isotopes parameters (delta13C of dissolved
      organic and inorganic carbons in water) in addition to multivariate analysis
      techniques. The use of conventional and alternative parameters together with
      multivariate analysis showed that cells of the residues are at different phases
      of stabilization of the organic matter and probably already at C3 of the
      methanogenic phase of decomposition. In addition, the data showed that organic
      matter stabilization ponds present in the landfill are efficient and improve the
      quality of the leachate. Enrichment of the heavy 13C isotope in both surface and
      groundwater suggested contamination in two sampling sites.

PMID- 29459206
TI  - Structure-based design and biological evaluation of inhibitors of the pseudomonas
      aeruginosa heme oxygenase (pa-HemO).

PMID- 29459207
TI  - A small group of sulfated benzofurans induces steady-state submaximal inhibition
      of thrombin.
AB  - Despite the development of promising direct oral anticoagulants, which are all
      orthosteric inhibitors, a sizable number of patients suffer from bleeding
      complications. We have hypothesized that allosterism based on the heparin-binding
      exosites presents a major opportunity to induce sub-maximal inhibition of
      coagulation proteases, thereby avoiding/reducing bleeding risk. We present the
      design of a group of sulfated benzofuran dimers that display heparin-binding site
      dependent partial allosteric inhibition of thrombin against fibrinogen (DeltaY =
      55-75%), the first time that a small molecule (MW  < 800) has been found to
      thwart macromolecular cleavage by a monomeric protease in a controlled manner.
      The work leads to the promising concept that it should be possible to develop
      allosteric inhibitors that reduce clotting, but do not completely eliminate it,
      thereby avoiding major bleeding complications that beset anticoagulants today.

PMID- 29459208
TI  - Water-soluble polyol-methanofullerenes as mitochondria-targeted antioxidants:
      Mechanism of action.
AB  - The mechanism of an antioxidant action of water-soluble polyol -
      methanofullerenes C60[C9H10O4(OH)4]6 and C60[C13H18O4(OH)4]6 as the mild
      uncouplers of an oxidative phosphorylation and respiration is postulated.
      According to this mechanism, hydroxyl group of methanofullerenols can be
      protonated under excess of protons in the intermembrane space of hyperpolarized
      mitochondria. Protonation of fullerene derivatives is confirmed by the decrease
      in their negative Zeta potential in the pH below 5.4. Heavily protonated
      methanofullerenols become positively charged and move into the mitochondrial
      matrix. As a consequence, the proton gradient is dissipated, which causes a
      decrease in mitochondrial transmembrane potential (DeltaPsim) and reduction in
      ROS production.

PMID- 29459209
TI  - 7alpha,15-Dihydroxydehydroabietic acid from Pinus koraiensis inhibits the
      promotion of angiogenesis through downregulation of VEGF, p-Akt and p-ERK in
      HUVECs.
AB  - Pinus koraiensis pinecones are considered an undesired waste by-product of the
      processing of seeds. However, recent studies of the potential anti-tumor effects
      of the pinecones have led to increasing interest in their chemical constituents.
      The present study examined the potential antiangiogenic effects of the
      constituents of pinecones and further characterized their underlying mechanisms
      of action. Chemical investigation of a water extract of P. koraiensis pinecones
      led to the isolation and identification of the eight main components including
      five diterpenoids (1-5), two monoterpenes (6,7) and a phenolic acid (8). The
      structure of the compounds was determined by spectroscopic analysis of NMR
      spectra and LC/MS analysis. Of the isolated compounds, 7alpha,15
      dihydroxydehydroabietic acid (5) significantly inhibited the promotion of
      angiogenesis in human umbilical vein endothelial cells (HUVECs). Compound 5
      inhibited angiogenesis through downregulation of the VEGF, p-Akt and p-ERK
      signaling pathways. These results provide experimental evidence of a novel
      biological activity of 7alpha,15-dihydroxydehydroabietic acid (5) as a potential
      antiangiogenic substance. This study also suggests that compound 5 could
      potentially be a useful adjuvant therapeutic substance for cancer prevention and
      treatment.

PMID- 29459211
TI  - A new approach to formulating and appraising drug policy: A multi-criterion
      decision analysis applied to alcohol and cannabis regulation.
AB  - BACKGROUND: Drug policy, whether for legal or illegal substances, is a
      controversial field that encompasses many complex issues. Policies can have
      effects on a myriad of outcomes and stakeholders differ in the outcomes they
      consider and value, while relevant knowledge on policy effects is dispersed
      across multiple research disciplines making integrated judgements difficult.
      METHODS: Experts on drug harms, addiction, criminology and drug policy were
      invited to a decision conference to develop a multi-criterion decision analysis
      (MCDA) model for appraising alternative regulatory regimes. Participants
      collectively defined regulatory regimes and identified outcome criteria
      reflecting ethical and normative concerns. For cannabis and alcohol separately,
      participants evaluated each regulatory regime on each criterion and weighted the
      criteria to provide summary scores for comparing different regimes. RESULTS: Four
      generic regulatory regimes were defined: absolute prohibition, decriminalisation,
      state control and free market. Participants also identified 27 relevant criteria
      which were organised into seven thematically related clusters. State control was
      the preferred regime for both alcohol and cannabis. The ranking of the regimes
      was robust to variations in the criterion-specific weights. CONCLUSION: The MCDA
      process allowed the participants to deconstruct complex drug policy issues into a
      set of simpler judgements that led to consensus about the results.

PMID- 29459210
TI  - Archaea diversity in vegetation gradients from the Brazilian Cerrado.
AB  - We used 16S rRNA sequencing to assess the archaeal communities across a gradient
      of Cerrado. The archaeal communities differed across the gradient. Crenarcheota
      was the most abundant phyla, with Nitrosphaerales and NRPJ as the predominant
      classes. Euryachaeota was also found across the Cerrado gradient, including the
      classes Metanocellales and Methanomassiliicoccaceae.

PMID- 29459212
TI  - Drug affordability-potential tool for comparing illicit drug markets.
AB  - BACKGROUND: The importance of illicit drug price data and making appropriate
      adjustments for purity has been repeatedly highlighted for understanding illicit
      drug markets. The European Monitoring Centre for Drugs and Drug Addiction
      (EMCDDA) has been collecting retail price data for a number of drug types
      alongside drug-specific purity information for over 15 years. While these data
      are useful for a number of monitoring and analytical purposes, they are not
      without their limitations and there are circumstances where additional adjustment
      needs to be considered. This paper reviews some conceptual issues and measurement
      challenges relevant to the interpretation of price data. It also highlights the
      issues with between-country comparisons of drug prices and introduces the concept
      of affordability of drugs, going beyond purity-adjustment to account for varying
      national economies. METHODS: Based on a 2015 European data set of price and
      purity data across the heroin and cocaine retail markets, the paper demonstrates
      a new model for drug market comparative analysis; calculation of drug
      affordability is achieved by applying to purity-adjusted prices 2015 Price Level
      Indices (PLI, Eurostat). RESULTS: Available data allowed retail heroin and
      cocaine market comparison for 27 European countries. The lowest and highest
      unadjusted prices per gram were observed for heroin: in Estonia, Belgium, Greece
      and Bulgaria (lowest) and Finland, Ireland, Sweden and Latvia (highest); for
      cocaine: the Netherlands, Belgium and the United Kingdom (lowest) and Turkey,
      Finland, Estonia and Romania (highest). The affordability per gram of heroin and
      cocaine when taking into account adjustment for both purity and economy
      demonstrates different patterns. CONCLUSION: It is argued that purity-adjusted
      price alone provides an incomplete comparison of retail price across countries.
      The proposed new method takes account of the differing economic conditions within
      European countries, thus providing a more sophisticated tool for cross-national
      comparisons of retail drug markets in Europe. Future work will need to examine
      other potential uses of the drug affordability tool. LIMITATIONS: The limitations
      of this measure reflect primarily the limitations of the constituent data; in
      addition to issues inherent in collecting accurate data on illicit markets,
      analysis that relies on data collected from multiple countries is susceptible to
      discrepancies in data collection practices from country to country.

PMID- 29459213
TI  - Maximal-intensity exercise does not fully restore muscle pyruvate dehydrogenase
      complex activation after 3 days of high-fat dietary intake.
AB  - BACKGROUND & AIMS: Exercise activates muscle pyruvate dehydrogenase complex
      (PDC), but moderate intensity exercise fails to fully activate muscle PDC after
      high-fat diet [1]. We investigated whether maximal intensity exercise overcomes
      this inhibition. METHODS: Quadriceps femoris muscle biopsy samples were obtained
      from healthy males at rest, and after 46 and 92 electrically-evoked maximal
      intermittent isometric contractions, which were preceded by 3 days of either low-
      (18%) or high- (69%) isocaloric dietary fat intake (LFD and HFD, respectively).
      RESULTS: The ratio of PDCa (active form) to total PDCt (fully activated) at rest
      was 50% less after HFD (0.32 +/- 0.01 vs 0.15 +/- 0.01; P < 0.05). This ratio
      increased to 0.77 +/- 0.06 after 46 contractions (P < 0.001) and to 0.98 +/- 0.07
      after 92 contractions (P < 0.001) in LFD. The corresponding values after HFD were
      less (0.54 +/- 0.06; P < 0.01 and 0.70 +/- 0.07; P < 0.01, respectively). Resting
      muscle acetyl-CoA and acetylcarnitine content was greater after HFD than LFD
      (both P < 0.05), but their rate of accumulation in the former was reduced during
      contraction. Muscle lactate content after 92 contractions was 30% greater after
      HFD (P < 0.05). Muscle force generation during contraction was no different
      between interventions, but HFD lengthened muscle relaxation time (P < 0.05).
      Daily urinary total carnitine excretion after HFD was 2.5-fold greater than after
      LFD (P < 0.01). CONCLUSIONS: A bout of maximal intense exercise did not overcome
      dietary fat-mediated inhibition of muscle pyruvate dehydrogenase complex
      activation, and was associated with greater muscle lactate accumulation, as a
      result of lower PDC flux, and increased muscle relaxation time.

PMID- 29459214
TI  - Reply-Letter to the Editor-Superiority of new predictive equation for resting
      energy expenditure.

PMID- 29459215
TI  - Saponins from seeds of Genus Camellia: Phytochemistry and bioactivity.
AB  - Camellia seeds have been traditionally used as oil raw materials in Asia, and are
      known for a wide spectrum of applications. Oleanane-type triterpene saponins are
      the major specialised metabolites in Camellia seeds, and more than seventy
      saponins have been isolated and characterized. These natural compounds have
      caught much attention due to their various biological and pharmacological
      activities, including modulation of gastrointestinal system, anti-cancer, anti
      inflammation, anti-microorganism, antioxidation, neuroprotection, hypolipidemic
      effects, foaming and detergence, as well as helping the accumulation of
      pollutants by plants. These compounds have a promising application in medicine,
      agriculture, industry and environmental protection. The present paper summarized
      the information from current publications on Camellia seed saponins, with a focus
      on the advances made in chemical structures, determination methods, bioactivities
      and toxicity. We hope this article will stimulate further investigations on these
      compounds.

PMID- 29459216
TI  - Anti-inflammatory flavone and chalcone derivatives from the roots of Pongamia
      pinnata (L.) Pierre.
AB  - A phytochemical study on the roots of Pongamia pinnata (L.) Pierre yielded 52
      flavonoids, including four previously undescribed flavone and four previously
      undescribed chalcone derivatives. The structures of the isolated compounds were
      determined on the basis of the 1D, 2D NMR, and mass spectroscopic data. The
      absolute configurations of the compounds were assigned via the specific rotation,
      Mosher's method, as well as the electronic circular dichroism (ECD) spectra. All
      the isolates were evaluated for their inhibitory effects on NO production in LPS
      stimulated BV-2 microglial cells. Ten compounds showed significant inhibitory
      effects against NO production, comparable to the positive control, dexamethasone.

PMID- 29459218
TI  - Clinical and Angiographic Predictors of Mortality in Sudden Cardiac Arrest
      Patients Having Cardiac Catheterisation: A Single Centre Registry.
AB  - BACKGROUND: Immediate cardiac catheterisation (CC) is recommended in ST-elevation
      myocardial infarction (STEMI) following sudden cardiac arrest (SCA). Guidelines
      advise urgent CC for SCA patients without-STEMI, at clinician discretion. We
      examined the clinical and angiographic factors predicting mortality in SCA
      patients having CC. METHODS: Consecutive SCA patients having CC at Liverpool
      Hospital, Sydney (January 2011-September 2015) were retrospectively analysed.
      Patient data were retrieved from hospital records, and angiographic SYNTAX scores
      (SS) were quantified online. Independent predictors of mortality were derived
      using multivariate logistic analysis. RESULTS: The study cohort comprised 104 SCA
      patients; mean age 61+/-12years, and 79% male. Immediate CC (<2hours post-SCA)
      was performed in 35% overall. Compared to the without-STEMI subgroup, STEMI
      patients had more ventricular fibrillation (91 vs 50%; p<0.0001), and higher mean
      peak serum high-sensitivity troponin-T (8.25+/-14.7 vs 1.97+/-6.13 ug/L;
      p=0.006); in the context of higher median SS (18 vs 6.5; p=0.002) and target
      lesion SS (tSS, 10 vs 0; p<0.001). Percutaneous coronary intervention (PCI; 75 vs
      23%; p<0.0001) and target vessel revascularisation (11 vs 0%; p=0.005) were more
      frequent for STEMI. All-cause mortality was 39%, at 1.3+/-1.5years follow-up.
      Independent mortality predictors were: delayed CC (HR 4.08), serum lactate
      >7mmol/L (HR 3.47), and tSS (HR 1.05). CONCLUSIONS: Elevated serum lactate, tSS,
      and delayed CC, were predictive of longer-term mortality in SCA patients having
      CC. Late CC in patients without-STEMI suggest scope for improvement in real-world
      systems of care. Closer scrutiny of target lesion complexity may aid
      prognostication in SCA survivors.

PMID- 29459217
TI  - Better together: Developmental screening and monitoring best identify children
      who need early intervention.
AB  - BACKGROUND: Widely recommended developmental surveillance methods include
      developmental monitoring (DM) and development screening (DS). Much research has
      been done on DS, but very little research has compared the effectiveness of DM
      and DS together. OBJECTIVES: To investigate the relationship between DM and DS in
      Part C early intervention (EI) service receipt. METHODS: Authors used data from
      the 2007/2008 and 2011/2012 National Survey of Children's Health (NSCH). Authors
      report the prevalence of children aged 10 months to 3 years who received (a) DM
      only, (b) DS only, (c) both DM and DS, and (c) no DM or DS across survey years.
      Authors compare the odds of EI receipt across these groups. RESULTS: During both
      periods, estimated EI receipt prevalence was higher for children receiving both
      DM and DS (8.38% in 2007/2008; 6.47% in 2011/2012) compared to children receiving
      no DM or DS (1.31% in 2007/2008; 1.92% in 2011/2012), DM alone (2.74% in
      2007/2008; 2.70% in 2011/2012), or DS alone (3.59% in 2007/2008; 3.09% in
      2011/2012) (for both time frames, p < .05). From 2007/2008 to 2011/2012, the
      proportion of children receiving DS only and both DM and DS increased, while
      children receiving DM only and no DM or DS decreased. CONCLUSIONS: Children
      receiving DM and DS together were more likely to receive EI compared to children
      receiving DM alone, DS alone, or neither DM nor DS. These findings support the
      AAP recommendations indicating that DM and DS are complementary strategies for
      improving early identification and linkage to EI for young children.

PMID- 29459219
TI  - Home blood pressure-guided antihypertensive therapy in chronic kidney disease:
      more data are needed.
AB  - In the era of newly introduced hypertension guidelines recommending lower blood
      pressure (BP) targets for drug-treated hypertensives, the necessity for optimized
      management of hypertension becomes even more urgent. The concept of home BP
      guided antihypertensive therapy is for long suggested as a simple and feasible
      approach to improve BP control rates and optimize the management of hypertension.
      Home BP-guided antihypertensive therapy is particularly applicable to
      hypertensives with chronic kidney disease (CKD) for several reasons including the
      following: (1) difficult-to-control BP and high BP variability in the CKD
      setting; (2) poor accuracy of office BP in determining hypertension control
      status and detecting "white-coat" and "masked" hypertension; (3) poor value of
      routine office BP recordings in predicting the longitudinal progression of target
      organ damage; and (4) superiority of home BP over office BP recordings in
      prognosticating the risk of incident end-stage renal disease or death. The
      concept of home BP-guided antihypertensive therapy is even more relevant for
      those on hemodialysis, given the high intradialytic and interdialytic BP
      variability and poor value of conventional peridialytic BP recordings in
      estimating the actual BP load recorded outside of dialysis with the use of home
      or ambulatory BP monitoring. Randomized trials comparing home BP-guided
      antihypertensive therapy versus usual care are warranted to prove the feasibility
      and effectiveness of this therapeutic approach and convince clinicians for using
      home BP monitoring as the standard of care when managing hypertension,
      particularly in people with CKD or end-stage renal disease.

PMID- 29459220
TI  - Varying blood pressure in children: a diagnostic quandary interpreting the Fourth
      Report.
AB  - Fourth Report guidelines on pediatric blood pressure (BP) are not clear when
      defining hypertension in children as "an average systolic BP and/or diastolic BP
      >= 95th percentile for gender, age, and height on >= 3 occasions." We aimed to
      determine the prevalence of pediatric hypertension in a screening population
      based on two different guideline interpretations. Prevalence of hypertension
      among 2094 students at four Houston area schools was calculated based on the
      summation or sustained model definition from Fourth Report guidelines. Summation
      hypertension definition required the single average of the BPs recorded across
      three visits to be elevated. Sustained hypertension definition required BP at
      each of three visits to be elevated. Hypertension prevalence by the summation
      method was 7%, whereas sustained prevalence was only 3.3%. Nearly a quarter of
      students had varying BP and were not classifiable by the sustained method but
      most would be classified as normal or prehypertensive by the summation method.
      The prevalence of hypertension among adolescents doubled depending on the
      interpretation of Fourth Report guidelines. Although methods in research studies
      can be clearly examined on publication of results, it is unknown which
      interpretation method is being used in clinical practice.

PMID- 29459221
TI  - Unsung and understudied: plastids involved in secondary growth.
AB  - Plastids represent the only subcellular compartment where aromatic amino acid
      precursors for lignin can be synthesized during secondary growth in vascular
      plants. Despite this, aside from a general shared understanding that plastid
      localized metabolism occurs during secondary growth, virtually no research has
      been performed on understanding their biology. Of particular importance will be
      insight into their ontogeny, morphology and ultrastructure, and (given the
      complex cytonuclear communication required) their nuclear-encoded and organellar
      encoded regulation. Updating and integrating this knowledge will contribute to
      our fundamental understanding of a ubiquitous developmental process in vascular
      plants, and a major terrestrial carbon sink, as well as carbon-related plant
      biotechnology. Given available evidence, we propose a new name for a distinct
      plastid derivative-the 'xyloplast', is required.

PMID- 29459222
TI  - Early life nutrition, glycemic and anthropometric profiles of children exposed to
      gestational diabetes mellitus in utero.

PMID- 29459223
TI  - Ambulatory practice of dermatologists in Taiwan: A nationwide survey.
AB  - BACKGROUND: Skin diseases are among the most common public health problems and
      cause a significant burden. For policymakers and clinicians, comprehensive and
      detailed information is necessary to better allocate resources needed to care for
      skin diseases. This study was conducted to characterize the ambulatory practice
      of dermatologists in Taiwan. METHODS: The study data were drawn from the datasets
      of Taiwan's National Health Insurance Research Database for 2013, with 623,614
      records of ambulatory care visits representing 1/500 of all the claims in Taiwan
      for 2013. The analysis of these visits included the patient demographics,
      diagnoses, prescriptions, and procedures. RESULTS: We identified 31,547 visits to
      dermatologic clinics, which accounted for 5.1% of all the ambulatory care visits
      in 2013. The three most commonly encountered diseases were contact dermatitis and
      other eczema, unspecified cause (34.3%, n = 10,811), acne (17.3%, n = 5452), and
      dermatophytosis (12.9%, n = 4065). Topical glucocorticoids (38.8%, n = 12,248),
      systemic antihistamines (35.4%, n = 11,172), and systemic antibiotics (15.2%, n =
      4809) were the three most commonly prescribed drug categories. Clobetasol, a very
      potent glucocorticoid, was the most commonly prescribed medication (20.9%, n =
      6579). In 22.9% of visits (n = 7248), combined glucocorticoid/antifungal
      preparations were prescribed. CONCLUSION: This study characterizes the current
      state of ambulatory dermatologic care in Taiwan. The results raise concerns about
      the misuse of very potent glucocorticoids and combined glucocorticoid/antifungal
      preparations in dermatologic practices.

PMID- 29459224
TI  - Hepatoblastoma incidence in Taiwan: A population-based study.
AB  - BACKGROUND: The incidence of hepatoblastoma is not well known in Taiwan. The goal
      of this study was to investigate the incidence rates of hepatoblastoma by age and
      sex. METHODS: The data of patients with hepatoblastoma diagnosed from 1995 to
      2012 were obtained from the population-based Taiwan Cancer Registry. Incidence
      rates of hepatoblastoma according to sex and age were analyzed. This study
      employed the published methods of International Agency for Research on Cancer to
      calculate the age-standardized incidence rates (ASIRs), standard errors, 95%
      confidence intervals (CIs), and standardized incidence rate ratios (SIRRs).
      RESULTS: In total, 211 patients were diagnosed with hepatoblastoma during the 18
      year study period. The ASIR was 0.76 per million person-years. Hepatoblastoma was
      predominantly diagnosed in children (n = 184, 87.2%). By contrast,
      adolescents/adults (n = 10, 4.7%) and elderly people (n = 17, 8.1%) were rarely
      affected. The incidence peaked at ages 0-4 years with corresponding ASIR of 7.3
      per million person-years. A significant male predilection was only found in
      children and elderly people, with male-to-female SIRRs of 1.23 and 1.89,
      respectively. During 1995-2012, the overall incidence of hepatoblastoma
      significantly increased only in children (annual percent change: 7.4%, 95% CI
      3.9%-11.1%, p < 0.05) and specifically in boys (annual percent change: 6.5%, 95%
      CI 1.9%-11.2%, p < 0.05). CONCLUSION: Only 27 patients aged >= 15 years with
      hepatoblastoma were identified in this study, the existence of adult
      hepatoblastoma still requires novel molecular tools to elucidate. The association
      between the upward trend of hepatoblastoma incidence in boys and increased
      survival of prematurity in Taiwan warrants further investigations.

PMID- 29459225
TI  - Improvement of overactive bladder symptoms: Is correction of the paravaginal
      defect in anterior vaginal wall prolapse necessary?
AB  - BACKGROUND: To explore the relationship between overactive bladder (OAB) symptoms
      and paravaginal defects (PVDs), and to identify the necessity of PVD repair by
      transvaginal mesh (TVM) for the treatment of OAB symptoms. METHODS: A
      retrospective clinical study of 30 women with advanced cystocele with limited
      apical and posterior vaginal wall prolapse was conducted to identify any changes
      in OAB symptoms following a single Perigee procedure. Prolapse was assessed using
      the pelvic organ prolapse quantification (POP-Q) system, and paravaginal defects
      were identified by sonography. Complete urodynamic examination was performed
      prior to and one year after operation. All patients completed the overactive
      bladder questionnaire pre- and postoperatively for a quantitative assessment of
      OAB symptoms. RESULTS: All patients showed a significant improvement at points Aa
      and Ba in the POP-Q system. The results of the administered questionnaire
      revealed statistically significant improvement postoperatively. The difference of
      OAB symptoms between the group with PVDs and that with central defects was not
      statistically significant (p = 0.67). Moreover, no statistically significant
      improvement of OAB symptoms in the group with repaired PVDs was observed
      postoperatively (p = 0.42). CONCLUSION: Statistical improvements of symptoms
      exist after Aa and Ba points recovery as evaluated by POP-Q system regardless of
      PVD existence identified by sonography. Repairing PVD did not show significantly
      improve the severity of OAB symptoms in objective urodynamic data or subjective
      questionnaire data. The superiority of TVM in PVD repair to manage OAB symptoms
      seems not manifest.

PMID- 29459226
TI  - The Lactobacillus and herpes simplex virus type 2 infection.

PMID- 29459228
TI  - Factors associated with the implementation of community-based peer-led health
      promotion programs: A scoping review.
AB  - Peer education is growing in popularity as a useful health promotion strategy.
      However, optimal conditions for implementing peer-led health promotion programs
      (HPPs) remain unclear. This scoping review aimed to describe factors that can
      influence implementation of peer-led HPPs targeting adult populations. Five
      databases were searched using the keywords "health promotion/prevention",
      "implementation", "peers", and related terms. Studies were included if they
      reported at least one factor associated with the implementation of community
      based peer-led HPPs. Fifty-five studies were selected for the analysis. The
      method known as "best fit framework synthesis" was used to analyze the factors
      identified in the selected papers. Many factors included in existing
      implementation conceptual frameworks were deemed applicable to peer-led HPPs.
      However, other factors related to individuals, programs, and implementation
      context also emerged from the analysis. Based on this synthesis, an adapted
      theoretical framework was elaborated, grounded in a complex adaptive system
      perspective and specifying potential mechanisms through which factors may
      influence implementation of community-based peer-led HPPs. Further research is
      needed to test the theoretical framework against empirical data. Findings from
      this scoping review increase our knowledge of the optimal conditions for
      implementing peer-led HPPs and thereby maximizing the benefits of such programs.

PMID- 29459229
TI  - Evaluating the implementation of Check & Connect in various school settings: Is
      intervention fidelity necessarily associated with positive outcomes?
AB  - There are numerous school dropout prevention programs. However, few of them have
      undergone a rigorous implementation evaluation to understand their effects. This
      research presents two studies that evaluated the intervention fidelity and
      differential effects of Check & Connect (C&C), a targeted school dropout
      prevention program aimed at promoting student engagement and achievement. A total
      of 145 elementary school students (Study 1) and 200 secondary school students
      (Study 2) from two French-Canadian school boards (regional districts grouping
      elementary and secondary schools) received the C&C intervention for two years. In
      both studies, a clinical monitoring form was used to compare the intervention
      fidelity of each program component and active ingredient with what was initially
      planned. The relation between intervention fidelity and the effects of C&C on
      student engagement and achievement was analyzed using multiple linear
      regressions. Overall, the results show that intervention fidelity varies across
      elementary and secondary schools from one component to another and from one site
      to another. Furthermore, the association between the fidelity of each component
      and positive outcomes varies, depending on the implementation site. This
      evaluation supports the relevance of every component of C&C to favor engagement
      and academic achievement among at-risk elementary and secondary school students,
      while suggesting that the importance of certain program components may vary,
      depending on contextual influences on implementation and outcomes.

PMID- 29459227
TI  - Hypoxia enhances H2O2-mediated upregulation of hepcidin: Evidence for NOX4
      mediated iron regulation.
AB  - The exact regulation of the liver-secreted peptide hepcidin, the key regulator of
      systemic iron homeostasis, is still poorly understood. It is potently induced by
      iron, inflammation, cytokines or H2O2 but conflicting results have been reported
      on hypoxia. In our current study, we first show that pronounced (1%) and mild
      (5%) hypoxia strongly induces hepcidin in human Huh7 hepatoma and primary liver
      cells predominantly at the transcriptional level via STAT3 using two hypoxia
      systems (hypoxia chamber and enzymatic hypoxia by the GOX/CAT system). SiRNA
      silencing of JAK1, STAT3 and NOX4 diminished the hypoxia-mediated effect while a
      role of HIF1alpha could be clearly ruled out by the response to hypoxia-mimetics
      and competition experiments with a plasmid harboring the oxygen-dependent
      degradation domain of HIF1alpha. Specifically, hypoxia drastically enhances the
      H2O2-mediated induction of hepcidin strongly pointing towards an oxidase as
      powerful upstream control of hepcidin. We finally provide evidences for an
      efficient regulation of hepcidin expression by NADPH-dependent oxidase 4 (NOX4)
      in liver cells. In summary, our data demonstrate that hypoxia strongly
      potentiates the peroxide-mediated induction of hepcidin via STAT3 signaling
      pathway. Moreover, oxidases such as NOX4 or artificially overexpressed urate
      oxidase (UOX) can induce hepcidin. It remains to be studied whether the peroxide
      STAT3-hepcidin axis simply acts to continuously compensate for oxygen
      fluctuations or is directly involved in iron sensing per se.

PMID- 29459231
TI  - Contributions of burner, pan, meat and salt to PM emission during grilling.
AB  - Grilling ground beef meat was conducted in two locations at Nazarbayev
      University, Kazakhstan. The experiments were designed such that only particles
      from beef meat were isolated. A similar experimental protocol was applied at both
      locations. The average particle number and mass emission rates for grilling pure
      meat itself (excluding particles from pan and burner) were found to be 9.4 *
      1012(SD = 7.2 * 1012 particle min-1 and 7.6 * 10 (SD = 6.3 * 10) mg.min-1,
      respectively. The PM emissions (number and mass) from the burner were found to be
      negligible compared to the pan and meat emissions. Ultrafine particle (UFP)
      concentrations from the heated pan itself were comparable to those of grilled
      meat. However, the particle mass concentrations from the pan itself were
      negligible. Approximately an hour of continuous heating resulted in zero
      emissions from the pan.

PMID- 29459230
TI  - Associations of long-term fine particulate matter exposure with prevalent
      hypertension and increased blood pressure in older Americans.
AB  - BACKGROUND: Hypertension is a highly prevalent cardiovascular risk factor. It is
      possible that air pollution, also an established cardiovascular risk factor, may
      contribute to cardiovascular disease through increasing blood pressure. Previous
      studies evaluating associations between air pollution and blood pressure have had
      mixed results. METHODS: We examined the association between long-term (one-year
      moving average) air pollutant exposures, prevalent hypertension and blood
      pressure in 4121 older Americans (57+ years) enrolled in the National Social
      Life, Health, and Aging Project. We estimated exposures to PM2.5 using spatio
      temporal models and used logistic regression accounting for repeated measures to
      evaluate the association between long-term average PM2.5 and prevalence odds of
      hypertension. We additionally used linear regression to evaluate the associations
      between air pollutants and systolic, diastolic, mean arterial, and pulse
      pressures. Health effect models were adjusted for a number of demographic, health
      and socioeconomic covariates. RESULTS: An inter-quartile range (3.91 MUg/m3)
      increase in the one-year moving average of PM2.5 was associated with increased:
      Odds of prevalent hypertension (POR 1.24, 95% CI: 1.11, 1.38), systolic blood
      pressure (0.93 mm Hg, 95% CI: 0.05, 1.80) and pulse pressure (0.89 mm Hg, 95% CI:
      0.21, 1.58). Dose-response relationships were also observed. CONCLUSIONS: PM2.5
      was associated with increased odds of prevalent hypertension, and increased
      systolic pressure and pulse pressure in a cohort of older Americans. These
      findings add to the growing evidence that air pollution may be an important risk
      factor for hypertension and perturbations in blood pressure.

PMID- 29459232
TI  - Arsenic methylation capacity in relation to nutrient intake and genetic
      polymorphisms in one-carbon metabolism.
AB  - BACKGROUND: Nutrients and genetic polymorphisms participating in one-carbon
      metabolism may explain interindividual differences in inorganic arsenic (iAs)
      methylation capacity, which in turn may account for variations in susceptibility
      to iAs-induced diseases. OBJECTIVES: 1) To evaluate the association between
      polymorphisms in five one-carbon metabolism genes (FOLH1 c.223 T > C, MTHFD1
      c.1958 G > A, MTHFR c.665 C > T, MTR c.2756 A > G, and MTRR c.66 A > G) and iAs
      methylation capacity; 2) To assess if previously reported associations between
      nutrient intake and iAs methylation capacity are modified by those polymorphisms.
      METHODS: Women (n = 1027) exposed to iAs in Northern Mexico were interviewed.
      Blood and urine samples were collected. Nutrient dietary intake was estimated
      using a validated food frequency questionnaire. iAs methylation capacity was
      calculated from urinary iAs species (iAs, monomethylarsonic acid [MMA] and
      dimethylarsinic acid [DMA]) measured by high performance liquid chromatography
      (HPLC-ICP-MS). One polymorphism in each of the five genes evaluated was genotyped
      by allelic discrimination. Multivariable linear regression models were used to
      evaluate if genetic polymorphisms modified the associations between iAs
      methylation capacity parameters and nutrient intake. RESULTS: The median (min
      max) concentration of total arsenic (TAs) was 20.2 (1.3-2776.0) ug/g creatinine
      in the study population. Significant interactions for iAs metabolism were only
      found with FOLH1 c.223 T > C polymorphism and vitamin B12 intake, so that CT and
      CC genotype carriers had significantly lower %iAs, and higher DMA/iAs with an
      increased vitamin B12 intake, as compared to carriers of wild-type TT.
      CONCLUSION: Differences in dietary nutrient intake and genetic variants in one
      carbon metabolism may jointly influence iAs methylation capacity. Confirmation of
      these interactions in other populations is warranted.

PMID- 29459233
TI  - Qualitative and quantitative control of pediatric syrups using Nuclear Magnetic
      Resonance and chemometrics.
AB  - Several flavoring and sweetening agents added to excipient of pediatric syrups
      are not declared in the package leaflet. Therefore, the aim of this study was to
      develop a non-target, simple, and precise method for qualitative and quantitative
      evaluation of pediatric syrups using NMR spectroscopy combined with chemometrics.
      This approach allowed the identification of several added compounds as citric
      acid, cyclamate, ethanol, glycerol, propylene glycol, saccharin, sorbitol,
      fructose, glucose, and sucrose. Among the sugared syrups, sucrose was the main
      carbohydrate with approximately 59.1%, and for sweetened syrups, glycerol with
      25.5%. The ethanol was found with highest concentration of 4.0%, approximately.
      In addition, some syrups presented both sugar and sweetener, which is
      inconsistent according to the purpose of the addition. Consequently,
      institutional structures of countries as Brazil that are in charge of public
      health should put additional compliance pressure on pharmaceutical companies to
      clearly declare in package leaflet the presence and exact amount of the main
      compounds (at least) existent in the pediatric excipients.

PMID- 29459234
TI  - A simple and sensitive HPLC-MS/MS method for quantification of eggmanone in rat
      plasma and its application to pharmacokinetics.
AB  - Allosteric phosphodiesterase 4 (PDE4) inhibitors are highly sought after due to
      their important anti-inflammatory and anti-cancer therapeutic effects. We
      recently identified Eggmanone, an extraordinarily selective allosteric PDE4
      inhibitor displaying favorable drug properties. However, a specific analytic
      method of Eggmanone in serum and its pharmacokinetics have not been reported yet.
      In this study, we developed a rapid and sensitive high performance liquid
      chromatography-mass spectrometric (HPLC-MS/MS) method to determine Eggmanone
      concentrations in rat plasma. This assay method was validated in terms of
      specificity, linearity, sensitivity, accuracy, precision, matrix effect, recovery
      and stability, and was applied to a pharmacokinetic study in rats following
      intravenous injection of Eggmanone at doses of 1 and 3 mg/kg. The lower limit of
      quantification (LLOQ) of this assay was 5 ng/mL and the linear calibration curve
      was acquired with R2 > 0.99 between 5 and 1000 ng/m. The intra-day and inter-day
      precision was evaluated with the coefficient of variations less than 11.09%,
      whereas the mean accuracy ranged from 98.38% to 105.13%. The assay method
      exhibited good recovery and negligible matrix effect. The samples were stable
      under all the experimental conditions. The plasma concentrations of Eggmanone
      were detected and quantified over 24 h with the terminal elimination half-live of
      3.57 +/- 1.80 h and 5.92 +/- 3.34 h for the low dose (1 mg/kg) and high dose (3
      mg/kg) respectively. In summary, the present method provides a robust, fast and
      sensitive analytical approach for quantification of Eggmanone in plasma and was
      successfully applied to a pharmacokinetic study in rats.

PMID- 29459235
TI  - Target and untargeted GC-MS based metabolomic study of mouse optic nerve and its
      potential in the study of neurological visual diseases.
AB  - The optic nerve is made of highly specialized neurons and the energetic supply to
      their axons is crucial due to their great demand. The energy comes basically
      through the oxidative phosphorylation in the mitochondria, supported by glial
      cells metabolism. Mitochondrial dysfunction is a shared feature encountered
      within the optic neuropathies, including Leber's Hereditary Optic Neuropathy,
      Leigh's Syndrome, or Kjer's syndrome. In an effort to investigate the metabolic
      alterations produced within the optic nerve in a mutant mouse model of
      Neurological Visual Disease (NVD), a rapid, robust, and efficient one-single
      phase extraction methodology has been developed and validated for the GC-MS
      platform. Once the method was successfully validated for lactic acid and pyruvic
      acid as markers of an adequate optic nerve function, the protocol was applied to
      unveil the metabolomic signature of the wild-type mouse optic nerve. Along the
      chromatographic profile of the optic nerve, 94 peaks were identified and, to our
      knowledge, for the first time. Afterwards, a targeted metabolomics analysis was
      performed to quantify lactic acid and pyruvic acid in the NDV mice group (n = 8)
      and its corresponding wild-type (n = 8). Finally, an untargeted metabolomic study
      was carried out and univariate and multivariate data analyses showed 34 compounds
      modified in the optic nerve of the mouse with NVD mutation. Then, the metabolic
      reaction network of the identified metabolites highlighted alterations in the
      catabolism of proteins, TCA cycle, and urea cycle, reflecting a mitochondrial
      energetic dysfunction. Taken together, this metabolomic study has proven to be
      suited for the study of optic neuropathies.

PMID- 29459237
TI  - Post-encoding control of working memory enhances processing of relevant
      information in rhesus monkeys (Macaca mulatta).
AB  - Working memory is a system by which a limited amount of information can be kept
      available for processing after the cessation of sensory input. Because working
      memory resources are limited, it is adaptive to focus processing on the most
      relevant information. We used a retro-cue paradigm to determine the extent to
      which monkey working memory possesses control mechanisms that focus processing on
      the most relevant representations. Monkeys saw a sample array of images, and
      shortly after the array disappeared, they were visually cued to a location that
      had been occupied by one of the sample images. The cue indicated which image
      should be remembered for the upcoming recognition test. By determining whether
      the monkeys were more accurate and quicker to respond to cued images compared to
      un-cued images, we tested the hypothesis that monkey working memory focuses
      processing on relevant information. We found a memory benefit for the cued image
      in terms of accuracy and retrieval speed with a memory load of two images. With a
      memory load of three images, we found a benefit in retrieval speed but only after
      shortening the onset latency of the retro-cue. Our results demonstrate previously
      unknown flexibility in the cognitive control of memory in monkeys, suggesting
      that control mechanisms in working memory likely evolved in a common ancestor of
      humans and monkeys more than 32 million years ago. Future work should be aimed at
      understanding the interaction between memory load and the ability to control
      memory resources, and the role of working memory control in generating
      differences in cognitive capacity among primates.

PMID- 29459236
TI  - Toward rapid analysis, forecast and discovery of bioactive compounds from herbs
      by jointly using thin layer chromatography and ratiometric surface-enhanced Raman
      spectroscopy technique.
AB  - Conventional isolation and identification of active compounds from herbs have
      been extensively reported by using various chromatographic and spectroscopic
      techniques. However, how to quickly discover new bioactive ingredients from
      natural sources still remains a challenging task due to the interference of their
      similar structures or matrices. Here, we present a grand approach for rapid
      analysis, forecast and discovery of bioactive compounds from herbs based on a
      hyphenated strategy of thin layer chromatography and ratiometric surface-enhanced
      Raman spectroscopy. The performance of the hyphenated strategy is first evaluated
      by analyzing four protoberberine alkaloids, berberine (BER), coptisine (COP),
      palmatine (PAT) and jatrorrhizine (JAT), from a typical herb Coptidis Rhizoma as
      an example. It has been demonstrated that this coupling method can identify the
      four compounds by characteristic peaks at 728, 708, 736 and 732 cm-1, and
      especially discriminate BER and COP (with similar migration distances) by
      ratiometric Raman intensity (I708/I728). The corresponding limits of detection
      are 0.1, 0.05, 0.1 and 0.5 MUM, respectively, which are about 1-2 orders of
      magnitude lower than those of direct observation method under 254 nm UV lamp.
      Based on these findings, the proposed method further guides forecast and
      discovery of unknown compounds from traditional Chinese herb Typhonii Rhizoma.
      Results infer that two trace alkaloids (BER and COP) from the n-butanol extract
      of Typhonii Rhizoma are found for the first time. Moreover, in vitro experiments
      manifest that BER can effectively decrease the viability of human glioma U87
      cells by inducing cell cycle arrest in a concentration-dependent manner.

PMID- 29459238
TI  - Encoding of event roles from visual scenes is rapid, spontaneous, and interacts
      with higher-level visual processing.
AB  - A crucial component of event recognition is understanding event roles, i.e. who
      acted on whom: boy hitting girl is different from girl hitting boy. We often
      categorize Agents (i.e. the actor) and Patients (i.e. the one acted upon) from
      visual input, but do we rapidly and spontaneously encode such roles even when our
      attention is otherwise occupied? In three experiments, participants observed a
      continuous sequence of two-person scenes and had to search for a target actor in
      each (the male/female or red/blue-shirted actor) by indicating with a button
      press whether the target appeared on the left or the right. Critically, although
      role was orthogonal to gender and shirt color, and was never explicitly
      mentioned, participants responded more slowly when the target's role switched
      from trial to trial (e.g., the male went from being the Patient to the Agent). In
      a final experiment, we demonstrated that this effect cannot be fully explained by
      differences in posture associated with Agents and Patients. Our results suggest
      that extraction of event structure from visual scenes is rapid and spontaneous.

PMID- 29459240
TI  - Telehealth for Remote Stroke Management.
AB  - Stroke is a leading cause of adult disability and the fourth leading cause of
      death in Canada. Most strokes are ischemic and functional outcome is highly time
      dependent, making fast diagnosis and treatment initiation crucial. This poses a
      challenge in vast geographical areas where stroke neurology expertise is only
      available in urban centres. In this article we review the rationale for
      telestroke networks and their current implementation in Canada. Telestroke
      networks enable stroke-specific procedures to be performed by less experienced
      physicians under the guidance of stroke neurology experts. We also present
      evidence that the safety and effectiveness of intravenous alteplase in community
      hospitals in a telestroke network seems to be comparable with that achieved in
      dedicated stroke centres. It is thus a viable option to guarantee an aging
      population access to stroke care across large geographic regions with faster
      treatment and access to more advanced treatment options by means of transfer to a
      comprehensive centre if necessary. Although telestroke networks have an upfront
      implementation cost, they can lead to reduced direct and indirect costs for the
      health care system by reducing days spent in the hospital as well as disability
      with the need for long-term care. Telestroke networks can also be used for
      identification and enrollment of patients into emergency stroke trials and thus
      provide a more representative sample of the population and increase recruitment.
      Standardization of regional telestroke networks could lead to collaborations with
      larger data acquisitions for research purposes and quality control in the future.

PMID- 29459239
TI  - Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and
      Vascular Mechanisms.
AB  - Hypertension and type 2 diabetes are common comorbidities. Hypertension is twice
      as frequent in patients with diabetes compared with those who do not have
      diabetes. Moreover, patients with hypertension often exhibit insulin resistance
      and are at greater risk of diabetes developing than are normotensive individuals.
      The major cause of morbidity and mortality in diabetes is cardiovascular disease,
      which is exacerbated by hypertension. Accordingly, diabetes and hypertension are
      closely interlinked because of similar risk factors, such as endothelial
      dysfunction, vascular inflammation, arterial remodelling, atherosclerosis,
      dyslipidemia, and obesity. There is also substantial overlap in the
      cardiovascular complications of diabetes and hypertension related primarily to
      microvascular and macrovascular disease. Common mechanisms, such as upregulation
      of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, and
      activation of the immune system likely contribute to the close relationship
      between diabetes and hypertension. In this article we discuss diabetes and
      hypertension as comorbidities and discuss the pathophysiological features of
      vascular complications associated with these conditions. We also highlight some
      vascular mechanisms that predispose to both conditions, focusing on advanced
      glycation end products, oxidative stress, inflammation, the immune system, and
      microRNAs. Finally, we provide some insights into current therapies targeting
      diabetes and cardiovascular complications and introduce some new agents that may
      have vasoprotective therapeutic potential in diabetes.

PMID- 29459241
TI  - The Atherogenic Dyslipidemia Complex and Novel Approaches to Cardiovascular
      Disease Prevention in Diabetes.
AB  - Despite the effectiveness of low-density lipoprotein (LDL)-lowering strategies
      for the treatment of diabetic dyslipidemia, significant residual risk of
      atherosclerotic cardiovascular disease remains. Residual risk might in part be
      explained by lipid abnormalities that go beyond LDL cholesterol elevation,
      collectively termed the "atherogenic dyslipidemia complex (ADC)," consisting of
      hypertriglyceridemia, elevated small dense LDL particles, reduced high-density
      lipoprotein cholesterol, and high-density lipoprotein particle numbers, increased
      remnant lipoproteins, and postprandial hyperlipidemia. In this review, we briefly
      discuss the pathophysiology of the typical dyslipidemia that occurs in insulin
      resistant states including obesity, the metabolic syndrome, and type 2 diabetes.
      Lipid-modifying strategies including lifestyle modification, ezetimibe, statins,
      fibrates, niacin, and cholesteryl ester transfer protein inhibitors in treating
      ADC are discussed. With the advent of novel therapies involving antisense
      oligonucleotides and monoclonal antibodies, new targets can be specifically
      downregulated to potentially promote lipoprotein clearance or suppress
      production. We review novel approaches currently undergoing clinical testing and
      we speculate on their suitability for use in treating ADC for the prevention of
      atherosclerotic cardiovascular disease. In addition, future targets that might be
      considered for therapeutic development are discussed.

PMID- 29459242
TI  - Correlates of disclosure of sexual violence among Kenyan youth.
AB  - INTRODUCTION: Sexual violence (SV) against children is a global health and human
      rights issue that can have short and long-term consequences for health and
      wellbeing. Disclosing SV increases the likelihood that children can access health
      and protective services and receive psychosocial support. Research in high-income
      countries has found that child SV survivors are more likely to disclose when they
      are girls/women, experience fewer SV events, and experience SV perpetrated by a
      stranger. No studies have examined correlates of SV disclosure in Kenya.
      OBJECTIVE: The objective of this research was to assess the correlates of
      disclosing SV among Kenyan youth ages 13-24 who reported an SV experience before
      age 18. METHODS: In 2010, the Kenya Ministry of Gender, Children and Social
      Development, the U.S. Centers for Disease Control and Prevention's (CDC) Division
      of Violence Prevention, the UNICEF Kenya Country Office, and the Kenya National
      Bureau of Statistics (KNBS) conducted a national survey of violence against
      children. These data were used to conduct weighted logistic regression analyses
      to determine which factors were correlated with reporting SV disclosure. RESULTS:
      Among the 27.8% of girls/women and 14.5% of boys/men who reported SV before age
      18, 44.6% of girls/women and 28.2% of boys/men reported to have disclosed the
      experience. In weighted logistic regression analysis, the odds of disclosure were
      lower among survivors who were boys/men and among survivors who reported more SV
      events, and higher when any perpetrator was a family member. CONCLUSION: More
      context-specific research on SV disclosure among young people is needed globally.

PMID- 29459243
TI  - Applicability of Lactococcus hircilactis and Lactococcus laudensis as dairy
      cultures.
AB  - The aim of this study was to evaluate whether Lactococcus hircilactis and
      Lactococcus laudensis can be used as starter cultures. To this end, the two
      lactococci were characterized for traits of technological and functional
      interest. Tests in milk included growth at 20, 25, 30, and 37  degrees C, flavor
      production, antioxidant (AO) activity, folate and exopolysaccharide (EPS)
      production. At 30  degrees C, which resulted the best growth temperature for both
      strains, Lc. hircilactis and Lc. laudensis lowered the pH of the milk to 4.8 and
      5.5, respectively, after 24 h of incubation. Sugar and organic acid composition
      indicated a higher lactose utilization, coupled with a higher lactate
      accumulation, by Lc. hircilactis, while galactose was completely consumed by both
      species. Both strains showed a Cit- phenotype after growth in a selective medium
      containing citrate as the sole carbon source. Nevertheless, a small amount of
      citrate was used by both lactococci when grown in milk. The two strains were
      characterized by a different flavor production, showed high AO activity, and
      produced small amounts of EPS (~30 mg/L). Lactococcus laudensis showed a weak
      proteolytic activity while Lc. hircilactis was able to accumulate folate at
      levels four times higher than uninoculated milk. When the two lactococci were
      tested as starter cultures in small-scale cheesemaking trials, cheeses resulted
      of satisfying quality and contained amounts of ethanol, acetic acid, diacetyl and
      acetoin higher than controls, obtained using a commercial culture. The
      application of Lc. hircilactis and Lc. laudensis as aromatic cultures in
      cheesemaking is proposed.

PMID- 29459244
TI  - Antifungal activity of plant-derived compounds and their synergism against major
      postharvest pathogens of longan fruit in vitro.
AB  - The aim of this study was to find alternatives to conventional synthetic
      fungicides to control postharvest decay of longan fruit. The antifungal potential
      of thymol, carvacrol and trans-cinnamaldehyde was evaluated against four major
      longan pathogens, Lasiodiplodia spp., Phomopsis spp., Pestalotiopsis spp. and
      Geotrichum candidum, using vapor phase and direct contact methods. The vapor
      phase of all active compounds was more effective on fungal growth than direct
      contact. A volatile vapor of thymol and carvacrol had strong antifungal activity
      against the tested fungi, exhibiting minimum inhibitory concentration (MIC) in
      the range of 40 to 80 mg/L air; trans-cinnamaldehyde showed the least efficiency,
      with MIC ranging from 80 to 160 mg/L air for G. candidum and Phomopsis spp.,
      while it could not inhibit Lasiodiplodia spp. and Pestalotiopsis spp. at 160 mg/L
      air. The minimum fungicidal concentration (MFC) of thymol and carvacrol varied
      from 40 to 80 mg/L air, while trans-cinnamaldehyde completely inhibited the
      mycelial growth of the tested fungi at higher concentrations. Mycelial growth of
      all tested fungi decreased with increasing active compound concentration, except
      for trans-cinnamaldehyde. Thymol proved to be the most effective compound against
      the four tested fungi, with effective concentration 50 (EC50) of 5.68 +/- 0.59,
      6.86 +/- 0.52, 8.27 +/- 0.22 and 9.99 +/- 1.28 mg/L air for Lasiodiplodia spp.,
      Phomopsis spp., Pestalotiopsis spp. and G. candidum, respectively. Fungal growth
      curves were adequately fitted (0.958 < R2 < 0.996) by a modified Gompertz model.
      For all tested fungi, the lag phase (lambda) of fungal mycelia exposed to thymol
      and carvacrol increased, while the maximum colony diameter (A) and maximum growth
      rate (vm) decreased. A combination of thymol and carvacrol exhibited an
      antagonistic effect against G. candidum but an indifferent effect against
      Lasiodiplodia spp., Phomopsis spp. and Pestalotiopsis spp.

PMID- 29459245
TI  - The Surgical Apgar Score predicts outcomes of emergency abdominal surgeries both
      in fit and frail older patients.
AB  - : The Surgical Apgar Score (SAS) is a simple and rapid scoring system predicting
      postoperative mortality and morbidity. However, it remains unknown whether it
      might be useful in fit and frail older patients undergoing abdominal emergency
      surgery. METHODS: Consecutive patients >=65 years, needing emergency abdominal
      surgery were enrolled in this prospective study. Additionally to the SAS, the G8
      screening score was used to determine the frailty status. The logistic regression
      analysis was conducted investigating the association between the scores and 30
      day postoperative outcomes. RESULTS: The study sample comprised 315 older
      patients (165 female, 150 male) with a median age of 77 (range 65-100) years old.
      The prevalence of frailty was 60.3%. The most frequent surgical indications were
      acute cholecystitis, followed by ileus, complicated diverticulitis, ulcer
      perforation, complication of gastric cancer and other causes. The decreasing SAS
      was significantly associated with the increasing likelihood of both 30-day
      postoperative major complications (p < 0.01) and death (p < 0.01) both in fit and
      frail older patients. Multivariate analyses have identified the G8, frailty
      screening test, and the SAS score as independent factors that predict
      postoperative adverse events. The model combining both scores increased the
      discriminatory ability for 30-day postoperative major morbidity and mortality.
      CONCLUSION: The SAS confirmed to be a simple and powerful predictor of 30-day
      postoperative morbidity and mortality both in fit and frail older patients
      undergoing emergency abdominal surgery. The department allocation algorithm based
      of the combination of the G8 and the SAS may be considered as an option to
      improve the outcomes of older patients undergoing abdominal emergency surgery.

PMID- 29459246
TI  - Breast cancer among older women: The influence of age and cancer stage on
      survival.
AB  - PURPOSE OF STUDY: To describe the association between increasing age and survival
      among women aged over 65 years, diagnosed with breast cancer. MATERIALS AND
      METHODS: A historical prospective cohort study, comparing 3270 breast cancer
      patients to 13,163 non cancer age matched controls. Baseline characteristics and
      cancer data gathered from the Israeli Central Bureau of Statistics (1995), the
      Israel Cancer Registry (2000-2010). Baseline measurements included age,
      socioeconomic status. Cancer stage at diagnosis was clustered as stage I, stage
      II-III and metastatic. Cox Proportional Hazards regression models were used to
      determine Hazards Ratios (HR) for mortality. RESULTS: Between ages 65-69 and
      >=85, metastatic disease rose from 3.9% to 23.4% and stage I disease declined
      from 58.6% to 30.1%. At age 80-84, 50% life expectancy among controls, stage I,
      and stage II-III disease was 95,92 and 90 months respectively, compared to 2
      months for metastatic disease. Compared to controls, between the age 65-69 to
      >=85, adjusted HR's progressively decreased among subjects with stage I from HR
      0.96 (95% CI 0.69-1.33) to 0.60 (95%CI 0.36-1.01), stage II-III from HR 3.26
      (95%CI2.58-4.12) to HR 1.60 (95%CI 1.22-2.09), and metastatic disease from HR
      57.40 (95%CI 39.56-83.29) to HR 20.76 (95%CI 14.73-29.24). CONCLUSIONS: This
      study describes the increasingly poor prognosis and short life expectancy
      observed among women aged >=80 diagnosed with metastatic breast. In contrast, our
      findings confirm the positive prognosis associated with rising age, among older
      women presenting with stage I breast cancer, among whom survival was similar, if
      not slightly better, than non-cancer age matched controls.

PMID- 29459247
TI  - An exploratory factor analysis of inflammatory and coagulation markers associated
      with femoral artery atherosclerosis in the San Diego Population Study.
AB  - BACKGROUND AND AIMS: Several biomarkers of inflammation and coagulation have been
      implicated in lower extremity atherosclerosis. We utilized an exploratory factor
      analysis (EFA) to identify distinct factors derived from circulating inflammatory
      and coagulation biomarkers then examined the associations of these factors with
      measures of lower extremity subclinical atherosclerosis, including the ankle
      brachial index (ABI), common and superficial femoral intima-media thickness
      (IMT), and atherosclerotic plaque presence, burden, and characteristics. METHODS:
      The San Diego Population Study (SDPS) is a prospective, community-living, multi
      ethnic cohort of 1103 men and women averaged age 70. Regression analysis was used
      to assess cross-sectional associations between the identified groupings of
      biomarkers (factors) and the ABI and femoral artery atherosclerosis measurements.
      RESULTS: Two biomarker factors emerged from the factor analysis. Factor 1
      consisting of C-reactive protein (CRP), interleukin (IL)-6, and fibrinogen was
      significantly associated with higher odds (OR = 1.99, p < 0.01) of a borderline
      ABI value (0.91-0.99), while Factor 2 containing D-dimer and pentraxin (PTX)-3
      was significantly associated with higher common femoral artery (CFA) IMT (beta =
      0.23, p < 0.01) and lower ABI (beta = -0.03, p < 0.01). CONCLUSIONS: Two
      groupings of biomarkers were identified via EFA of seven circulating biomarkers
      of inflammation and coagulation. These distinct groups are differentially
      associated with markers of lower extremity subclinical atherosclerosis. Our
      findings suggest that high inflammatory and coagulation burden were better
      markers of more severe lower-extremity disease as indicated by low ABI rather
      than early atherosclerotic lesion development in the femoral artery.

PMID- 29459248
TI  - Impact of comorbidity and frailty on prognosis in colorectal cancer patients: A
      systematic review and meta-analysis.
AB  - INTRODUCTION: Colorectal cancer (CRC) is largely diagnosed at old age, when
      comorbidities and frailty are common and might be important prognostic factors of
      CRC. We aimed to systematically review epidemiological evidence on the prognostic
      role of comorbidity and frailty in CRC patients. METHODS: We systematically
      searched the PubMed and Web of Science databases up to August 08, 2017 for
      observational studies that used a standardized index to assess comorbidity or
      frailty, investigated and reported odds ratios (OR) or hazard ratios (HR) of
      their associations with any of the following CRC prognostic outcomes: thirty-day,
      overall or CRC-specific mortality and disease-free or recurrence-free survival.
      The study was conducted using standard meta-analysis methodology. RESULTS: Thirty
      seven cohort studies were identified and included in this review: 35 on
      comorbidity and 2 on frailty. Of the 35 studies, 13 with comparable methodology
      were eligible for a meta-analysis. Compared to CRC patients without comorbidity,
      those with mild/moderate and severe comorbidity had, respectively, a higher risk
      of 30-day (OR = 1.71; 95% confidence interval (CI): 1.26-2.31 and OR = 2.62; 95%
      CI: 1.97-3.47), overall (HR = 1.41; 95% CI: 1.23-1.62 and HR = 2.03; 95% CI: 1.76
      2.34), and CRC-specific mortality (HR = 1.06; 95% CI: 1.02-1.10 and HR = 1.14;
      95% CI: 1.04-1.23). Frail CRC patients showed higher overall mortality than non
      frail patients (HRrange: 2.60-3.39). CONCLUSIONS: Comorbidity and frailty are
      strong prognostic factors of survival in CRC patients apart from the commonly
      considered sociodemographic and tumor characteristics. Comprehensive geriatric
      assessment might help to optimize care of CRC patients, by improving early
      identification and management of comorbidities and geriatric syndromes.

PMID- 29459249
TI  - Associations between social capital and depression: A study of adult twins.
AB  - Social capital is associated with depression independently of individual-level
      risk factors. We used a sample of 1586 same-sex twin pairs to test the
      association between seven measures of social capital and two related measures of
      neighborhood characteristics with depressive symptoms accounting for uncontrolled
      selection factors (i.e., genetics and shared environment). All measures of
      cognitive social capital and neighborhood characteristics were associated with
      less depressive symptoms in between-twin analysis. However, only measures of
      cognitive social capital were significantly associated with less depressive
      symptoms within-pairs. These results demonstrate that cognitive social capital is
      associated with depressive symptoms free of confounding from genetic and
      environmental factors shared within twins.

PMID- 29459250
TI  - Adipose specific disruption of seipin causes early-onset generalised
      lipodystrophy and altered fuel utilisation without severe metabolic disease.
AB  - OBJECTIVE: Mutations to the BSCL2 gene disrupt the protein seipin and cause the
      most severe form of congenital generalised lipodystrophy (CGL). Affected
      individuals exhibit a near complete loss of white adipose tissue (WAT) and suffer
      from metabolic disease. Seipin is critical for adipocyte development in culture
      and mice with germline disruption to Bscl2 recapitulate the effects of BSCL2
      disruption in humans. Here we examined whether loss of Bscl2 specifically in
      developing adipocytes in vivo is sufficient to prevent adipose tissue development
      and cause all features observed with congenital BSCL2 disruption. METHODS: We
      generated and characterised a novel mouse model of Bscl2 deficiency in developing
      adipocytes (Ad-B2(-/-)) using the adipose-specific Adiponectin-Cre line. RESULTS:
      We demonstrate that Ad-B2(-/-) mice display early onset lipodystrophy, in common
      with congenital Bscl2 null mice and CGL2 patients. However, glucose intolerance,
      insulin resistance, and severe hepatic steatosis are not apparent. Food intake
      and energy expenditure are unchanged, but Ad-B2(-/-) mice exhibit significantly
      altered substrate utilisation. We also find differential effects of seipin loss
      between specific adipose depots revealing new insights regarding their varied
      characteristics. When fed a high-fat diet, Ad-B2(-/-) mice entirely fail to
      expand adipose mass but remain glucose tolerant. CONCLUSIONS: Our findings
      demonstrate that disruption of Bscl2 specifically in developing adipocytes is
      sufficient to cause the early-onset generalised lipodystrophy observed in
      patients with mutations in BSCL2. However, this significant reduction in adipose
      mass does not cause the overt metabolic dysfunction seen in Bscl2 knockout mice,
      even following a high-fat diet challenge.

PMID- 29459251
TI  - Prolyl carboxypeptidase in Agouti-related Peptide neurons modulates food intake
      and body weight.
AB  - OBJECTIVE: Prolyl carboxypeptidase (PRCP) plays a role in the regulation of
      energy metabolism by inactivating hypothalamic alpha-melanocyte stimulating
      hormone (alpha-MSH) levels. Although detected in the arcuate nucleus, limited
      PRCP expression has been observed in the arcuate POMC neurons, and its site of
      action in regulating metabolism is still ill-defined. METHODS: We performed
      immunostaining to assess the localization of PRCP in arcuate Neuropeptide
      Y/Agouti-related Peptide (NPY/AgRP) neurons. Hypothalamic explants were then used
      to assess the intracellular localization of PRCP and its release at the synaptic
      levels. Finally, we generated a mouse model to assess the role of PRCP in
      NPY/AgRP neurons of the arcuate nucleus in the regulation of metabolism. RESULTS:
      Here we show that PRCP is expressed in NPY/AgRP-expressing neurons of the arcuate
      nucleus. In hypothalamic explants, stimulation by ghrelin increased PRCP
      concentration in the medium and decreased PRCP content in synaptic extract,
      suggesting that PRCP is released at the synaptic level. In support of this,
      hypothalamic explants from mice with selective deletion of PRCP in AgRP neurons
      (PrcpAgRPKO) showed reduced ghrelin-induced PRCP concentration in the medium
      compared to controls mice. Furthermore, male PrcpAgRPKO mice had decreased body
      weight and fat mass compared to controls. However, this phenotype was sex
      specific as female PrcpAgRPKO mice show metabolic differences only when
      challenged by high fat diet feeding. The improved metabolism of PrcpAgRPKO mice
      was associated with reduced food intake and increased energy expenditure,
      locomotor activity, and hypothalamic alpha-MSH levels. Administration of SHU9119,
      a potent melanocortin receptor antagonist, selectively in the PVN of PrcpAgRPKO
      male mice increased food intake to a level similar to that of control mice.
      CONCLUSIONS: Altogether, our data indicate that PRCP is released at the synaptic
      levels and that PRCP in AgRP neurons contributes to the modulation of alpha-MSH
      degradation and related metabolic control in mice.

PMID- 29459252
TI  - Multimodal, noninvasive seizure network mapping software: A novel tool for
      preoperative epilepsy evaluation.
AB  - BACKGROUND: Despite rigorous preoperative evaluation, epilepsy surgery achieves
      seizure freedom in only two-thirds of cases. Current preoperative evaluation does
      not include a detailed network analysis despite the association of network-level
      changes with epilepsy. OBJECTIVE: We sought to create a software algorithm to map
      individualized epilepsy networks by combining noninvasive electroencephalography
      (EEG) source localization and nonconcurrent resting state functional magnetic
      resonance imaging (rsfMRI). METHODS: Scalp EEG and rsfMRI data were acquired for
      three sample cases: one healthy control case, one case of right temporal lobe
      epilepsy, and one case of bitemporal seizure onset. Data from rsfMRI were
      preprocessed, and a time-series function was extracted. Connection coefficients
      were used to threshold out spurious connections and model global functional
      networks in a 3D map. Epileptic discharges were localized using a forward model
      of cortical mesh dipoles followed by an empirical Bayesian approach of inverse
      source reconstruction and co-registered with rsfMRI. Co-activating brain regions
      were mapped. RESULTS: Three illustrative sample cases are presented. In the
      healthy control case, the software showed symmetrical global connectivity. In the
      right temporal lobe epilepsy case, asymmetry was found in the global connectivity
      metrics with a paucity of connectivity ipsilateral to the epileptogenic cortex.
      The superior longitudinal fasciculus, uncinate fasciculus, and commissural fibers
      connecting disparate and discontinuous cortical regions involved in the epilepsy
      network were visualized. In the case with bitemporal lobe epilepsy, global
      connectivity was symmetric. It showed a network of correlating cortical activity
      local to epileptogenic tissue in both temporal lobes. The network involved white
      matter tracks in a similar pattern to those seen in the right temporal case.
      CONCLUSIONS: This modeling algorithm allows better definition of the global brain
      network and potentially demonstrates differences in connectivity between an
      epileptic and a non-epileptic brain. This finding may be useful for mapping
      cortico-cortical connections representing the putative epilepsy networks. With
      this methodology, we localized the epileptogenic brain and showed network
      asymmetry and long-distance cortical co-activation. This software tool is the
      first to use a multimodal, nonconcurrent, and noninvasive approach to model and
      visualize the epilepsy network.

PMID- 29459253
TI  - A novel TaqMan(r) assay for Nosema ceranae quantification in honey bee, based on
      the protein coding gene Hsp70.
AB  - Nosema ceranae is now a widespread honey bee pathogen with high incidence in
      apiculture. Rapid and reliable detection and quantification methods are a matter
      of concern for research community, nowadays mainly relying on the use of
      biomolecular techniques such as PCR, RT-PCR or HRMA. The aim of this technical
      paper is to provide a new qPCR assay, based on the highly-conserved protein
      coding gene Hsp70, to detect and quantify the microsporidian Nosema ceranae
      affecting the western honey bee Apis mellifera. The validation steps to assess
      efficiency, sensitivity, specificity and robustness of the assay are described
      also.

PMID- 29459254
TI  - Application of a Monte Carlo method to the uncertainty assessment in in situ
      gamma-ray spectrometry.
AB  - In situ gamma-ray spectrometry has since the introduction of portable germanium
      detectors been a widely used method for the assessment of radionuclide ground
      deposition activity levels. It is, however, a method that is most often
      associated with fairly large and, more important, poorly known combined
      measurement uncertainties. In this work an uncertainty analysis of in situ gamma
      ray spectrometry in accordance with the Guide to the Expression of Uncertainty in
      Measurements is presented. The uncertainty analysis takes into account
      uncertainty contributions from the calibration of the detector system, the
      assumed activity distribution in soil, soil density, detector height and air
      density. As a result, measurement results from in situ gamma spectrometry will
      serve as a better basis for decision-making in e.g. radiological emergencies.

PMID- 29459255
TI  - Circulation of cosmogenic 22Na using the global monitoring network of the
      Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO).
AB  - Using a recently published global data set of 22Na and 7Be from the global
      monitoring network of the Comprehensive Nuclear-Test-Ban Treaty Organization
      (CTBTO), atmospheric circulation and stratosphere-troposphere interactions are
      examined. Cosmogenic 22Na has a half-life well-suited to environmental processes
      with durations from several months to a decade. Combined with corresponding 7Be
      observations, these two cosmogenic isotopes form a useful environmental tracer
      and new radiochronometer to study physical interactions of air masses in the
      stratosphere and troposphere.

PMID- 29459256
TI  - Evaluation of data quality at the National Cancer Registry of Ukraine.
AB  - BACKGROUND: Cancer notification has been mandatory in Ukraine since 1953, with
      the National Cancer Registry of Ukraine (NCRU) established in 1996. The aim of
      this study was to provide a comprehensive evaluation of the data quality at the
      NCRU. METHODS: Qualitative and semi-quantitative methods were used to assess the
      comparability, completeness, validity and timeliness of cancer incidence data
      from the NCRU for the period 2002-2012. RESULTS: Cancer registration procedures
      at the NCRU are in accordance with international standards and recommendations.
      Semi-quantitative methods suggested the NCRU's data was reasonably complete,
      although decreases in age-specific incidence and mortality rates in the elderly
      indicated some missing cases at older ages. The proportion of microscopically
      verified cases increased from 73.6% in 2002 to 82.3% in 2012, with death
      certificate-only (DCO) proportions stable at around 0.1% and unknown stage
      recorded in 9.6% of male and 7.5% of female solid tumours. Timeliness was
      considered acceptable, with reporting >99% complete within a turn-around time of
      15 months. CONCLUSION: While timely reporting of national data reflects the
      advantages of a mandatory data collection system, a low DCO% and observed age
      specific declines suggest possible underreporting of incidence and mortality
      data, particularly at older ages. Overall, the evaluation indicates that the data
      are reasonably comparable and thus may be used to describe the magnitude of the
      cancer burden in Ukraine. Given its central role in monitoring and evaluation of
      cancer control activities, ensuring the sustainability of NCRU operations
      throughout the process of healthcare system reform is of utmost importance.

PMID- 29459257
TI  - Effect of comorbidities on the course of multiple sclerosis.
AB  - OBJECTIVE: The clinical condition of multiple sclerosis (MS) patients depends not
      only on the course of MS but also on their lifestyle and comorbidities. This
      study aimed to assess the effect of selected comorbidities, lifestyle-related
      factors and clinical data available at the time of MS diagnosis, on the disease
      activity and the disability progression in patients with relapsing-remitting
      multiple sclerosis (RRMS). PATIENTS AND METHODS: Based on clinical relapses over
      a period of 12 months of observation and the results of MRI scans, 138 patients
      with RRMS were qualified into two groups: 'active' or 'stable' course of the
      disease. Patients from both groups were compared regarding the clinical data
      determined at diagnosis, comorbidities and lifestyle-related factors. Similar
      comparisons were carried out between patients with EDSS < 3 vs, patients with
      EDSS >= 3. RESULTS: No significant differences in comorbidities and lifestyle
      related data between the stable and active group were detected. Arterial
      hypertension, hyperlipidemia, higher BMI values, older age and a lower education
      level, were found more frequently in patients with EDSS >= 3. Oligoclonal bands,
      multifocal clinical manifestation as the first relapse, higher EDSS score and
      many T2 MRI lesions at the diagnosis were detected significantly more often in
      the active group. Motor or brainstem/cerebellum damage symptoms as the first
      relapse were observed more frequently in patients with EDSS >= 3. CONCLUSIONS:
      Cardiovascular diseases may exacerbate disability progression in MS patients.
      Relapses and radiological activity do not depend on chronic comorbidities.
      Clinical data available at the diagnosis may be useful in forecasting a distant
      course of MS.

PMID- 29459258
TI  - Chemical chromatin ubiquitylation.
AB  - Histone modifications dynamically regulate chromatin structure and function,
      thereby mediating many processes that require access to DNA. Chemical protein
      synthesis has emerged as a powerful approach for generating homogeneously
      modified histone analogues in workable amounts for subsequent incorporation into
      nucleosome arrays for biochemical, functional and structural studies. This short
      review focuses on the strength of total chemical protein synthesis and
      semisynthetic approaches to generate ubiquitylated histones in their native or
      non-native forms and the utility of these analogues to decode the role of
      ubiquitylation in epigenetics.

PMID- 29459259
TI  - DL-mandelic acid intercalated Zn-Al layered double hydroxide: A novel
      antimicrobial layered material.
AB  - DL-mandelic acid (MA) has been intercalated into Zn-Al layered double hydroxide
      (LDH) by an anion-exchange reaction. After intercalation of MA anions, the basal
      spacing of the LDH increased from 0.75 to 1.46 nm, suggesting that the MA anions
      were successfully intercalated into the interlayer galleries of the LDH. The
      structure and the thermal stability of the samples were characterized by XRD, FT
      IR, TG-DTA. Studies of MA release from ZnAl-MA-LDH in hydrochloric solution (pH =
      4) imply that ZnAl-MA-LDH is a better controlled release system than pure MA.
      Meanwhile, the mechanisms of slow release were assessed by using four commonly
      kinetic models. Finally, the antimicrobial activity of ZnAl-MA-LDH was tested
      against two kinds of bacteria and a fungus. The study confirms that the mandelic
      ions intercalated LDHs have the potential application as a slow release
      preservative in the future.

PMID- 29459260
TI  - Preferential adhesion of surface groups of Bacillus subtilis on gibbsite at
      different ionic strengths and pHs revealed by ATR-FTIR spectroscopy.
AB  - Adhesion of bacteria onto minerals is a ubiquitous process that plays a central
      role in many biogeochemical, microbiology and environmental processes in soil and
      sediment. Although bacterial adhesion onto soil minerals such as phyllosilicates
      and Fe-oxides have been investigated extensively, little is known about the
      mechanisms for bacterial attachment onto Al-oxides. Here, we explored the
      adhesion of Bacillus subtilis onto gibbsite (gamma-AlOOH) under various ionic
      strengths (1, 10, 50, and 100 mM NaCl) and pHs (pH 4, 7, and 9) by in-situ
      attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy.
      The time evolution of the peak intensities of the attached bacteria suggested
      that the adhesion underwent an initial rapid reaction followed by a slow pseudo
      first-order kinetic stage. Spectral comparison between the attached and free
      cells, together with the interaction energy calculated with the Derjaguin,
      Landau, Verwey, and Overbeek (DLVO) theory and the micro-morphology of bacteria
      gibbsite complexes, indicated that both electrostatic and chemical (bacterial
      groups such as phosphate and carboxyl covalently bind to gibbsite) interactions
      participated in the adhesion processes. Both solution ionic strength (IS) and pH
      impacted the spectra of attached bacteria, but the peak intensity of different
      bands changed differently with these two factors, showing a preferential adhesion
      of surface groups (phosphate, carboxyl, and amide groups) on gibbsite at
      different conditions. The diverse responses to IS and pH alteration of the forces
      (chemical bonds, electrostatic attractions, and the hydrophobic interactions)
      that essentially govern the adhesion might be responsible for the preferential
      adhesion. These results may help to better understand how bacteria adhere onto
      soil oxides at molecular scales.

PMID- 29459261
TI  - The immune response to CMV infection and vaccination in mice, monkeys and humans:
      recent developments.
AB  - The immune response to CMV is characterized by extremely large T cell and
      antibody responses that persist for a lifetime, but do not prevent superinfection
      with other CMV strains. This makes generation of a vaccine against CMV very
      difficult, but has facilitated development of CMV-vectored vaccines, which have
      shown promise in mouse tumor models and in monkey models of infectious disease.
      The serendipitous use of a mutant rhesus CMV vector for the SIV vaccine elicited
      extraordinary, CD8 T cell responses restricted by MHCII and non-classical MHCI
      molecules which apparently provide protection against SIV. CMV-specific CD8 T
      cell responses in the mouse model are driven by antigen and live out their lives
      primarily within the intravascular compartment.

PMID- 29459262
TI  - Soluble endoglin and hypercholesterolemia aggravate endothelial and vessel wall
      dysfunction in mouse aorta.
AB  - BACKGROUND AND AIMS: Increased plasma levels of soluble endoglin (sEng) were
      detected in patients with endothelial dysfunction-related disorders and
      hypercholesterolemia. In this study, we hypothesized that high levels of sEng
      accompanied by mild hypercholesterolemia could aggravate endothelial and vessel
      wall dysfunction and affect endoglin/eNOS signaling in mouse aorta. METHODS:
      Three-month-old female transgenic mice on CBAxC57BL/6J background, with high
      levels of sEng (Sol-Eng+high HFD), and their littermates with low levels of sEng
      (Sol-Eng+low HFD), were fed a high fat diet for six months. Plasma samples were
      used for biochemical, ELISA and Luminex analyses of total cholesterol, sEng and
      inflammatory markers. Functional parameters of aorta were assessed with wire
      myograph 620M. Western blot analyses of membrane endoglin/eNOS signaling and
      endothelial dysfunction/inflammation markers in aorta were performed. RESULTS:
      Functional analysis of aorta showed impaired KCl induced vasoconstriction,
      endothelial-dependent relaxation after the administration of acetylcholine as
      well as endothelial-independent relaxation induced by sodium nitroprusside in the
      Sol-Eng+high HFD group compared to the Sol-Eng+low HFD group. Ach-induced
      vasodilation after administration of l-NAME was significantly higher in the Sol
      Eng+high HFD group compared to the Sol-Eng+low HFD group. The expression of
      endoglin, p-eNOS/eNOS, pSmad2/3/Smad2/3 signaling pathway was significantly lower
      in the Sol-Eng+high HFD group compared to the Sol-Eng+low HFD group. CONCLUSIONS:
      The results indicate that long-term hypercholesterolemia combined with high
      levels of sEng leads to the aggravation of endothelial and vessel wall
      dysfunction in aorta, with possible alterations of the membrane endoglin/eNOS
      signaling, suggesting that high levels of soluble endoglin might be considered as
      a risk factor of cardiovascular diseases.

PMID- 29459263
TI  - Hyperlipidemia induces typical atherosclerosis development in Ldlr and Apoe
      deficient rats.
AB  - BACKGROUND AND AIMS: Low-density lipoprotein receptor (Ldlr) and apolipoprotein E
      (Apoe) knockout (KO) mice have been widely used as animal models of
      atherosclerosis. However, data suggested that it is difficult to develop typical
      atherosclerosis in rats. To this end, Ldlr and Apoe KO rats were generated and
      the potential to develop novel atherosclerosis models was evaluated. METHODS: We
      established Apoe/Ldlr single and double KO (DKO) rats via the CRISPR/Cas9 system
      in the same background. Phenotypes of dyslipidemia and atherosclerosis in these
      KO rats were systematically characterized. RESULTS: Knockout of either gene led
      to severe dyslipidemia and liver steatosis. Significant atherosclerotic plaques
      were observed in the abdominal aorta of all mutant rats fed a normal diet for 48
      weeks. Western diet greatly aggravated atherosclerosis and fatty liver. In
      addition, we found mononuclear cell infiltration in early lesions. Increased
      expression of inflammatory cytokines, as well as macrophage accumulation in
      lesions of mutants, was observed, indicating that mononuclear cell trafficking
      and endothelial inflammation affected atherogenesis. Moreover, mutant rats
      displayed a sex difference profile more similar to humans in which males had
      heavier plaque burdens than females. CONCLUSIONS: Deficiency of either Ldlr or
      Apoe genes induced hyperlipidemia, which promoted endothelial inflammation and
      led to typical atherosclerosis in rats on normal or Western diets. These models
      display certain advantages, which will benefit future investigations of
      atherosclerotic pathology and antiatherosclerotic therapeutics.

PMID- 29459264
TI  - Induction of microRNA-10a using retinoic acid receptor-alpha and retinoid x
      receptor-alpha agonists inhibits atherosclerotic lesion formation.
AB  - BACKGROUND AND AIMS: MicroRNA (miR)-10a is a shear-regulated miR with the lowest
      expression in vascular endothelial cells (ECs) in athero-susceptible regions with
      oscillatory shear stress (OS). The aim of this study is to elucidate the
      relationship between EC miR-10a and atherosclerosis and develop a hemodynamics
      based strategy for atherosclerosis treatment. METHODS: A combination of in vitro
      flow system and in vivo experimental animals was used to examine the functional
      roles of EC miR-10a and its clinical applications in atherosclerosis. RESULTS: En
      face staining showed that EC miR-10a is down-regulated in the inner curvature (OS
      region) of aortic arch in rats. Co-administration with retinoic acid receptor
      alpha (RARalpha)- and retinoid X receptor-alpha (RXRalpha)-specific agonists
      rescued EC miR-10a expression in this OS region. These effects of OS and
      RARalpha/RXRalpha-specific agonists on EC miR-10a expression were confirmed by
      the in vitro flow system, and were modulated by the RARalpha-histone deacetylases
      complex, with the consequent modulation in the downstream GATA6/vascular cell
      adhesion molecule (VCAM)-1 signaling cascade. Animal studies showed that miR-10a
      levels are decreased in both aortic endothelium of atherosclerotic lesions and
      blood plasma from apolipoprotein E-deficient (ApoE-/-) mice. In vivo induction of
      EC miR-10a by administration of RARalpha/RXRalpha-specific agonists protects ApoE
      /- mice from atherosclerosis through inhibition of GATA6/VCAM-1 signaling and
      inflammatory cell infiltration. CONCLUSIONS: Our findings indicate that down
      regulation of miR-10a in aortic endothelium and blood serum is associated with
      atherosclerosis, and miR-10a has potential to be developed as diagnostic molecule
      for atherosclerosis. Moreover, EC miR-10a induction by RARalpha/RXRalpha-specific
      agonists is a potential hemodynamics-based strategy for atherosclerosis
      treatment.

PMID- 29459265
TI  - Sleep characteristics and progression of coronary artery calcification: Results
      from the Heinz Nixdorf Recall cohort study.
AB  - BACKGROUND AND AIMS: Sleep characteristics are associated with incident
      cardiovascular diseases (CVD), but there is a lack of studies on the association
      between sleep characteristics and incidence/progression of coronary artery
      calcification (CAC). METHODS: In the Heinz Nixdorf Recall Study, a population
      based cohort study in Germany, CAC was assessed by electron-beam tomography at
      baseline and at 5-year follow-up. In an analysis set of 3043 subjects (age at
      baseline 45-74 years; 47% men), we fitted logistic and linear regression models
      to assess associations between self-rated sleep characteristics (nocturnal and
      total sleep duration; napping; various sleep disorders) and CAC incidence/CAC
      progression. Progression was measured as 5-year progression factor, as categories
      of absolute CAC change, and additionally characterized as rapid or slow compared
      to an extrapolation of baseline CAC values. RESULTS: We observed barely any
      association between sleep characteristics and CAC progression regardless of the
      chosen statistical approach; associations between sleep and CAC incidence were
      slightly larger, e.g., the geometric mean of the 5-year CAC progression factor
      was 6.8% (95% confidence interval: -9.5; 25.9) larger for <=5 h, 2.9% (-7.3;
      14.3) larger for 5.1-6.9 h and 7.1% (-2.4; 15.7) smaller for >=7.5 h total sleep
      compared to 7- <7.5 h total sleep. For subjects with any regular sleep disorder,
      the geometric mean of the 5-year CAC progression was 3.5% (-4.7; 11.2) smaller
      compared to subjects without any regular sleep disorder. CONCLUSIONS: In this
      German cohort study, sleep characteristics were barely associated with CAC
      progression.

PMID- 29459266
TI  - Risk factors for progression of coronary artery calcification in patients with
      chronic kidney disease: The CRIC study.
AB  - BACKGROUND AND AIMS: Coronary artery calcification (CAC) is common among patients
      with chronic kidney disease (CKD) and predicts the risk for cardiovascular
      disease (CVD). We examined the associations of novel risk factors with CAC
      progression among patients with CKD. METHODS: Among 1123 CKD patients in the
      Chronic Renal Insufficiency Cohort (CRIC) Study, CAC was measured in Agatston
      units at baseline and a follow-up visit using electron beam computed tomography
      or multidetector computed tomography. RESULTS: Over an average 3.3-year follow
      up, 109 (25.1%) participants without CAC at baseline had incident CAC and 124
      (18.0%) participants with CAC at baseline had CAC progression, defined as an
      annual increase of >=100 Agatston units. After adjustment for established
      atherosclerotic risk factors, several novel risk factors were associated with
      changes in CAC over follow-up. Changes in square root transformed CAC score
      associated with 1 SD greater level of risk factors were -0.20 (95% confidence
      interval, -0.31 to -0.10; p < 0.001) for estimated glomerular filtration rate,
      0.14 (0.02-0.25; p = 0.02) for 24-h urine albumin, 0.25 (0.15-0.34; p < 0.001)
      for cystatin C, -0.17 (-0.27 to -0.07; p < 0.001) for serum calcium, 0.14 (0.03
      0.24; p = 0.009) for serum phosphate, 0.24 (0.14-0.33; p < 0.001) for fibroblast
      growth factor-23, 0.13 (0.04-0.23; p = 0.007) for total parathyroid hormone, 0.17
      (0.07-0.27; p < 0.001) for interleukin-6, and 0.12 (0.02-0.22; p = 0.02) for
      tumor necrosis factor-alpha. CONCLUSIONS: Reduced kidney function, calcium and
      phosphate metabolism disorders, and inflammation, independent of established CVD
      risk factors, may progress CAC among CKD patients.

PMID- 29459267
TI  - Ankle brachial index and cognitive function among Hispanics/Latinos: Results from
      the Hispanic Community Health Study/Study of Latinos.
AB  - BACKGROUND AND AIMS: The Ankle-Brachial index (ABI) is a well-accepted measure of
      peripheral artery disease (arterial stenosis and stiffness) and has been shown to
      be associated with cognitive function and disorders; however, these associations
      have not been examined in Hispanics/Latinos. Therefore, we sought to examine
      relationships between ABI and cognitive function among diverse middle-age and
      older Hispanics/Latinos. METHODS: We used cross-sectional data on n = 7991
      participants aged 45-74 years, without stroke or coronary heart disease, from the
      Hispanic Community Health Study/Study of Latinos. Our primary outcome, global
      cognition (GC), was a continuous composite score of four cognitive domains
      (verbal learning and memory, verbal fluency, executive function, and mental
      status). Secondary outcomes were the individual tests representing these domains.
      The ABI was analyzed continuously and categorically with standard clinical cut
      points. We tested associations using generalized survey regression models
      incrementally adjusting for confounding factors. Age, sex, hypertension,
      diabetes, and dyslipidemia moderations were examined through interactions with
      the primary exposure. RESULTS: In age, sex, and education adjusted models,
      continuous ABI had an inverse u-shape association with worse GC. We found similar
      associations with measures of verbal learning and memory, verbal fluency,
      executive function, but not with low mental status. The associations were
      attenuated, but not completely explained, by accounting for the confounders and
      not modified by age, sex, education, and vascular disease risks. CONCLUSIONS: In
      addition to being a robust indicator of arterial compromise, our study suggests
      that abnormal ABI readings may also be useful for early signaling of subtle
      cognitive deficits.

PMID- 29459268
TI  - Gene-lifestyle interplay in type 2 diabetes.
AB  - Type 2 diabetes (T2D) is widespread, affecting the health of hundreds of millions
      worldwide. The disease results from the complex interplay of lifestyle factors
      acting on a backdrop of inherited DNA risk variants. Detecting and understanding
      biomarkers, whether genotypes or other downstream biological features that
      dictate a person's phenotypic response to different lifestyle exposures, may have
      tremendous utility in the prevention of T2D. Here, we explore (i) evidence of how
      human genetic adaptation to diverse local environments might interact with
      lifestyle factors in T2D, (ii) the key challenges facing the research area of
      gene*lifestyle interactions in T2D, and (iii) the solutions that might be pursued
      in future studies. Overall, many preliminary examples of such interactions exist,
      but none is sufficient to have a major impact on clinical decision making. Future
      studies, integrating genetics and other biological markers into regulatory
      networks, are likely to be necessary to facilitate the integration of genomics
      into lifestyle medicine in T2D.

PMID- 29459269
TI  - Study on antidepressant activity of chiisanoside in mice.
AB  - The antidepressant-like effect of chiisanoside from the leaves of Acanthopanax
      sessiliflorus was evaluated by using mice models of depression, forced swim test
      (FST) and tail suspension test (TST). The results showed that treatment with
      chiisanoside at dose of 5.0 mg/kg significantly decreased immobility time in the
      FST and TST. Pretreatment with haloperidol (a non-selective D2 receptor
      antagonist), bicuculline (a competitive GABA antagonist) and N-methyl-D-aspartic
      acid (NMDA, an agonist at the glutamate site) effectively reversed the
      antidepressant-like effect of chiisanoside (5.0 mg/kg). Moreover, chiisanoside
      treatment did not change the locomotor activity. And chiisanoside (5.0 mg/kg)
      also effectively increased the dopamine (DA) and gamma-aminobutyric acid (GABA)
      levels in mice brains exposed to the FST and TST in the co-treatment groups. Then
      we designed lipopolysaccharide (LPS)-induced antidepressant behavioral
      experiment, the results showed that LPS significantly increased immobility
      duration in the TST and FST. Chiisanoside administration could effectively reduce
      serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels; at
      the same time, the changes of related indexes of oxidative stress are improved,
      such as superoxide dismutase (SOD) and malondialdehyde (MDA). Moreover,
      chiisanoside effectively down-regulated brain-derived neurotrophic factor (BDNF),
      tropomyosin-related kinase B (TrkB) and nuclear factor-kappaB (NF-kappaB) in
      hippocampal. In conclusion, chiisanoside displayed significant antidepressant
      like effect, which was probably related to the DAergic, GABAergic and
      glutamatergic systems. And the mechanism of anti-depressant effect of
      chiisanoside might be via the alterations of animal behaviors, hippocampus
      inflammation, oxidative stress and neurotrophy, which might be attributed by the
      BDNF/TrkB/NF-kappaB pathway.

PMID- 29459270
TI  - Sparse representation for Lamb-wave-based damage detection using a dictionary
      algorithm.
AB  - Lamb waves are being investigated extensively for structural health monitoring
      (SHM) because of their characteristics of traveling long distances with little
      attenuation and sensitivity to minor local damage in structures. However, Lamb
      waves are dispersive, which results in the complex overlap of waveforms in the
      damage detection applications of the SHM community. This paper proposes a sparse
      representation strategy based on an l1-norm optimization algorithm for guided
      Lamb-wave-based inspections. A comprehensive dictionary is designed containing
      various waveforms under diverse conditions so that the received waveform can be
      decomposed into a spatial domain for the identification of damage location.
      Furthermore, the l1-norm optimization algorithm is employed to pursue the sparse
      solution related to the physical damage location. The functionality of the
      created dictionary is validated by both metal beam and composite wind turbine
      experiments. The results indicate a great potential for the proposed sparse
      representation using a dictionary algorithm, which provides an effective
      alternative approach for damage detection.

PMID- 29459271
TI  - A family of manganese complexes containing heterocyclic-based ligands with
      cytotoxic properties.
AB  - We describe the synthesis of three new manganese (II) complexes containing the
      bidentate ligands 2-(1-methyl-3-pyrazolyl)pyridine (pypz-Me) and ethyl 2-(3
      (pyridine-2-yl)-1H-pyrazol-1-yl)acetate (pypz-CH2COOEt), with formula [MnX2(pypz
      Me)2] (X = Cl-1, CF3SO3-2) and [Mn(CF3SO3)2(pypz-CH2COOEt)2] 3. Complexes 1-3
      have been characterized through analytical, spectroscopic and electrochemical
      techniques, as well as by monocrystal X-ray diffraction analysis. The complexes
      show a six-coordinated Mn(II) ion though different stereoisomers have been
      isolated for the three compounds. Complexes 1-3, together with the previously
      described compounds [MnCl2(pypz-H)2] 4, [Mn(CF3SO3)2(pypz-H)2] 5, [Mn(NO3)2(pypz
      H)2] 6, [MnCl2(H2O)2(pypz-H)2] 7 (pypz-H = 2-(3-pyrazolyl)pyridine) and
      ([Mn(CF3SO3)2((-)-L)2] 8, ((-)-L = (-)-pinene[5,6]bipyridine), were tested in
      vitro for cytotoxic activity against NCI-H460 and OVCAR-8 cancer cell lines. The
      geometry of a specific compound does not seem to influence its activity in a
      significant extent. However, among the tested compounds those that display
      hydrophobic substituents on the pyrazole ring and triflate ions as labile ligands
      show the best antiproliferative properties. Specifically, compound 8 containing
      the pinene-bipyridine ligand presents an antiproliferative activity similar to
      that of cisplatin and higher than that of carboplatin, and displays selectivity
      for tumour cells. Its antiproliferative effect is due to the generation of ROS
      species that allow the compound to interact with DNA.

PMID- 29459272
TI  - Reactions of ferric hemoglobin and myoglobin with hydrogen sulfide under
      physiological conditions.
AB  - Ferric hemoglobin (metHb) and myoglobin (metMb), present at low levels in vivo,
      have been recently found to oxidize hydrogen sulfide (H2S) in excess, thus
      potentially contributing to removal of toxic H2S in blood and heart,
      respectively. Here, we present a kinetic and thermodynamic study of the reaction
      of metHb and metMb with H2S under physiological conditions, i.e. at low H2S
      concentrations and with protein in excess of H2S. We show here that both proteins
      react with sub-stoichiometric H2S:heme ratios following two processes: a fast
      reversible binding of H2S to ferric heme that prevails at high H2S and a slow
      heme reduction to the ferrous state that prevails at low H2S. While these two
      processes are fast for metMb, H2S-induced heme reduction is slow for metHb and
      the metHb-H2S complex once formed is therefore relatively stable. We find that
      metHb binds H2S reversibly and cooperatively with a pH-dependent ligand affinity
      that is within the physiological range of H2S concentrations found in blood.
      Stopped-flow kinetics show identical association rate constants for H2S at
      varying pH, demonstrating that H2S and not HS- enters the ferric heme pocket.
      Dissociation rates of the metHb-H2S complex increase when decreasing pH,
      consistent with the pH-dependent affinity. Taken together, these data are
      consistent with a novel biological role of metHb as a H2S carrier in the blood,
      in parallel with the oxygen carrier function of the much more abundant ferrous
      Hb. In contrast, metMb in the heart could participate to redox-signaling
      involving H2S.

PMID- 29459273
TI  - New antitumor anthra[2,3-b]furan-3-carboxamides: Synthesis and structure-activity
      relationship.
AB  - Chemical modifications of the anthraquinone scaffold are aimed at optimization of
      this exceptionally productive class of antitumor drugs. In particular, our
      previously reported anthra[2,3-b]furan-3-carboxamides demonstrated a high
      cytotoxic potency in cell culture and in vivo. In this study, we expanded our
      series of anthra[2,3-b]furan-3-carboxamides by modifying the key functional
      groups and dissected the structure-activity relationship within this chemotype.
      The majority of new compounds inhibited the growth of mammalian tumor cell lines
      at submicromolar to low micromolar concentrations. We found that 4,11-hydroxy
      groups as well as the carbonyl moiety in the carboxamide fragment were critical
      for cytotoxicity whereas the substituent at the 2-position of anthra[2,3-b]furan
      was not. Importantly, the new derivatives were similarly potent against wild type
      cells and their variants resistant to doxorubicin due to P-glycoprotein (Pgp)
      expression or p53 inactivation. The most cytotoxic derivatives 6 and 9 attenuated
      plasmid DNA relaxation by topoisomerase 1. Finally, we demonstrated that 6 and 9
      at 1 MUM induced intracellular oxidative stress, accumulation in G2/M phase of
      the cell cycle, and apoptosis in gastric carcinoma cell lines regardless of their
      p53 status. These results further substantiate the potential of anthra[2,3
      b]furan-3-carboxamides as antitumor drug candidates.

PMID- 29459274
TI  - Design, synthesis and biological evaluation of tetrahydronaphthyridine
      derivatives as bioavailable CDK4/6 inhibitors for cancer therapy.
AB  - CDK4/6 pathway is an attractive chemotherapeutic target for antitumor drug
      discovery and development. Herein, we reported the structure-based design and
      synthesis of a series of novel tetrahydronaphthyridine analogues as selective
      CDK4/6 inhibitors. Compound 5 was identified as a hit and then systematically
      structure optimization study was conducted. These efforts led to compound 28,
      which exhibited excellent in vitro potencies against CDK4/6 enzymatic activity
      with high selectivity over CDK1, and against Colo-205 cell growth. The compound
      demonstrated favorable in vitro metabolic and robust mice pharmacokinetic
      properties. In Colo-205 xenograft models, compound 28 showed potent tumor growth
      inhibition with acceptable toxic effects, which could serve as a novel anticancer
      agent for further preclinical study.

PMID- 29459275
TI  - Original antileishmanial hits: Variations around amidoximes.
AB  - In continuation to our previous findings on amidoximes' antiparasitic activities,
      a new series of 23 original derivatives was designed and obtained by convergent
      synthesis. First, new terminal alkenes were synthesized by cross-coupling
      reaction. Then, cyclization was performed between terminal alkenes and beta
      ketosulfones using manganese(III) acetate reactivity. Twenty-three amidoximes
      were tested for their in vitro activity against Leishmania amazonensis
      promastigotes and their toxicity on murine macrophages. Seven of the tested
      compounds exhibited an antileishmanial activity at lower than 10 MUM with
      moderate to low toxicity. Six of these molecules showed activity at lower than 10
      MUM against promastigotes and toxicity at higher than 50 MUM were selected and
      evaluated for their activity against intracellular Leishmania amazonensis
      amastigotes. Modulating chemical substituents in position 2 of dihydrofuran
      highly influenced their antileishmanial activities. The introduction of a methyl
      or trifluoromethyl group on the benzene ring of the benzyl group had a positive
      influence on activity without significantly increasing toxicity (52, 59, 60).

PMID- 29459276
TI  - Cytotoxicity of eta6-areneruthenium-based molecules to glioblastoma cells and
      their recognition by multidrug ABC transporters.
AB  - A new series of amphiphilic eta6-areneruthenium(II) compounds containing
      phenylazo ligands (group I: compounds 1a, 1b, 2a and 2b) and phenyloxadiazole
      ligands (group II: compounds 3a, 3b, 4a and 4b) were synthesized and
      characterized for their anti-glioblastoma activity. The effects of the
      amphiphilic eta6-areneruthenium(II) complexes on the viability of three human
      glioblastoma cell lines, U251, U87MG and T98G, were evaluated. The azo-derivative
      ruthenium complexes (group I) showed high cytotoxicity to all cell lines, whilst
      most oxadiazole-derivative complexes (group II) were less cytotoxic, except for
      compound 4a. The cationic complexes 2a, 2b and 4b were more cytotoxic than the
      neutral complexes. Compounds 2a and 2b caused a significant reduction in the
      percentage of cells in the G0/G1 phase, with concomitant increases in the G2/M
      phase and fragmented DNA in the T98G cell line. The eta6-areneruthenium(II)
      compounds were also tested in cell lines that overexpress the multidrug ABC
      transporters P-gp, MRP1 and ABCG2. Compounds 2b and 4a were substrates for the P
      gp protein, with resistance indexes of 8.6 and 1.9, respectively. Compound 2b was
      also a substrate for ABCG2 and MRP1 proteins, with lower resistance indexes (1.8
      and 1.6, respectively). The contribution of multidrug ABC transporters to the
      cytotoxicity of compound 2b in T98G cells was evidenced, since verapamil (a
      characteristic inhibitor of MRP1) increased the cytotoxicity of compound 2b at
      concentrations up to 20 MUmol L-1, whilst GF120918 and Ko143 (specific inhibitors
      of P-gp and ABCG2, respectively) had no significant effect. In addition, we
      showed that compound 2b interacts with glutathione (GSH), which could explain its
      cellular efflux by MRP1. Our results showed that the amphiphilic eta6
      areneruthenium(II) complexes are promising anti-glioblastoma compounds,
      especially compound 2b, which was cytotoxic for all three cell lines, although it
      is transported by the three main multidrug ABC transporters.

PMID- 29459277
TI  - Targeting G-quadruplex DNA structures in the telomere and oncogene promoter
      regions by benzimidazole-carbazole ligands.
AB  - Recent studies support the idea that G-quadruplex structures in the promoter
      regions of oncogenes and telomere DNA can serve as potential therapeutic targets
      in the treatment of cancer. Accordingly, several different types of organic small
      molecules that stabilize G-quadruplex structures and inhibit telomerase activity
      have been discerned. Here, we describe the binding of benzimidazole-carbazole
      ligands to G-quadruplex structures formed in G-rich DNA sequences containing the
      promoter regions of human c-MYC, c-KIT1, c-KIT2, VEGF and BCL2 proto-oncogenes.
      The fluorescence spectroscopic data indicate that benzimidazole-carbazole ligands
      bind and stabilize the G-quadruplexes in the promoter region of oncogenes. The
      molecular docking studies provide insights into the mode and extent of binding of
      this class of ligands to the G-quadruplexes formed in oncogene promoters. The
      high stability of these G-quadruplex structures was validated by thermal
      denaturation and telomerase-catalyzed extension of the 3' end. Notably,
      benzimidazole-carbazole ligands suppress the expression of oncogenes in cancer
      cells in a dose-dependent manner. We anticipate that benzimidazole-carbazole
      ligands, by virtue of their ability to stabilize G-quadruplex structures in the
      promoter regions of oncogenes, might reduce the risk of cancer through the loss
      of function in the proteins encoded by these genes.

PMID- 29459278
TI  - Alkynyl-containing phenylthiazoles: Systemically active antibacterial agents
      effective against methicillin-resistant Staphylococcus aureus (MRSA).
AB  - The promising activity of phenylthiazoles against multidrug-resistant bacterial
      pathogens, in particular MRSA, has been hampered by their limited systemic
      applicability, due to their rapid metabolism by hepatic microsomal enzymes,
      resulting in short half-lives. Here, we investigated a series of phenylthiazoles
      with alkynyl side-chains that were synthesized with the objective of improving
      stability to hepatic metabolism, extending the utility of phenylthiazoles from
      topical applications to treatment of a more invasive, systemic MRSA infections.
      The most promising compounds inhibited the growth of clinically-relevant isolates
      of MRSA in vitro at concentrations as low as 0.5 MUg/mL, and exerted their
      antibacterial effect by interfering with bacterial cell wall synthesis via
      inhibition of undecaprenyl diphosphate synthase and undecaprenyl diphosphate
      phosphatase. We also identified two phenylthiazoles that successfully eradicated
      MRSA inside infected macrophages. In vivo PK analysis of compound 9 revealed
      promising stability to hepatic metabolism with a biological half-life of ~4.5 h.
      In mice, compound 9 demonstrated comparable potency to vancomycin, and at a lower
      dose (20 mg/kg versus 50 mg/kg), in reducing the burden of MRSA in a systemic,
      deep-tissue infection, using the neutropenic mouse thigh-infection model.
      Compound 9 thus represents a new phenylthiazole lead for the treatment of MRSA
      infections that warrants further development.

PMID- 29459279
TI  - Cyclic peptide inhibitors of lysine-specific demethylase 1 with improved potency
      identified by alanine scanning mutagenesis.
AB  - Lysine-specific demethylase 1 (LSD1) is a chromatin-remodeling enzyme that plays
      an important role in cancer. Over-expression of LSD1 decreases methylation at
      histone 3 lysine 4, and aberrantly silences tumor suppressor genes. Inhibitors of
      LSD1 have been designed as chemical probes and potential antitumor agents. We
      recently reported the cyclic peptide 9, which potently and reversibly inhibits
      LSD1 (IC50 2.1 MUM; Ki 385 nM). Systematic alanine mutagenesis of 9 revealed
      residues that are critical for LSD1 inhibition, and these mutated peptides were
      evaluated as LSD1 inhibitors. Alanine substitution at positions 2, 3, 4, 6 and 11
      17 preserved inhibition, while substitution of alanine at positions 8 and 9
      resulted in complete loss of activity. Cyclic mutant peptides 11 and 16 produced
      the greatest LSD1 inhibition, and 11, 16, 27 and 28 increased global H3K4me2 in
      K562 cells. In addition, 16, 27 and 28 promoted significant increases in H3K4me2
      levels at the promoter sites of the genes IGFBP2 and FEZ1. Data from these LSD1
      inhibitors will aid in the design of peptidomimetics with improved stability and
      pharmacokinetics.

PMID- 29459280
TI  - The moderating impact of childhood adversity profiles and conflict on
      psychological health and suicidal behaviour in the Northern Ireland population.
AB  - Childhood adversities are key etiological factors in the onset and persistence of
      psychopathology. In Northern Ireland the Troubles also impacted on the
      population's psychological health. This study used data from the Northern Ireland
      Study of Health and Stress a collaborative epidemiological study which used the
      WMH-CIDI to assess mental health disorders in a nationally representative sample
      (Part 2, n = 1986). The aims of the study were to assess co-occurrences of
      childhood adversities and investigate the impact of adversity profiles and
      conflict experience on psychopathology and suicidal behaviour. Latent Class
      Analysis uncovered 3 discrete childhood adversity profiles, a low, medium, and
      high risk class. Individuals from higher risk adversity profiles displayed
      significantly increased odds of having psychological problems, with conflict
      exposure also impacting on psychopathology. However, the study revealed that the
      impact of conflict exposure on suicidal behaviour was moderated by latent class
      membership and that some adversity may actually be protective. The findings
      highlight the need to consider that, while adversity can have a negative impact
      on psychopathology, a lack of adversity early in life may hinder some people from
      developing adequate coping strategies. Further research is required to identify
      adversity patterns and other interacting factors that are protective.

PMID- 29459281
TI  - Synthesis and evaluation of a novel urea-based 68Ga-complex for imaging PSMA
      binding in tumor.
AB  - INTRODUCTION: Prostate specific membrane antigen (PSMA) is a well-established
      target for diagnostic and therapeutic applications for prostate cancer. It is
      know that [68Ga]PSMA 11 ([68Ga]Glu-NH-CO-NH-Lys(Ahx)-HBED-CC) is the most well
      studied PET imaging agent for detecting over expressed PSMA binding sites of
      tumors in humans. In an effort to provide new agents with improved
      characteristics for PET imaging, we report a novel [68Ga]-Glu-NH-CO-NH-Lys(Ahx)
      linker-HBED-CC conjugate with a novel O-(carboxymethyl)-L-tyrosine, as the linker
      group. METHODS: Radiosynthesis was performed by a direct method. In vitro binding
      and cell internalization of [68Ga]10 was investigated in PSMA positive LNCaP cell
      lines. Biodistribution and MicroPET imaging studies were performed in LNCaP tumor
      bearing mice. RESULTS: In vitro binding to LNCaP cells showed that natGa labeled
      O-(carboxymethyl)-L-tyrosine conjugate, [natGa]10, displayed excellent affinity
      and specificity (IC50 = 16.5 nM) a value comparable to that of PSMA 11. In vitro
      cell binding and internalization showed excellent uptake and retention; [68Ga]10
      displayed significantly higher cellular internalization than [68Ga]PSMA 11 (12.5
      vs 7.4% ID/106 cells at 1 h). Biodistribution studies in LNCaP tumor-bearing mice
      exhibited a high specific uptake in PSMA expressing tumors and fast clearance in
      normal organs (19.7 tumor/blood; 20.7 tumor/muscle at 1 h after iv injection).
      MicroPET imaging studies in mice confirmed that [68Ga]10 displayed excellent
      uptake and distinctive tumor localization, which was blocked by iv injection of a
      competing drug, 2-PMPA. CONCLUSIONS: The preliminary results strongly suggest
      that [68Ga]10 may be promising candidates as a PET imaging radiotracer for
      detecting PSMA expression in prostate cancer.

PMID- 29459282
TI  - Embodiment of social roles and thinness as a form of capital: A qualitative
      approach towards understanding female obesity disparities in Chile.
AB  - Obesity in Chile disproportionately affects women of low socioeconomic status
      (SES). Research has shown that ideals of body size and differences in perceived
      social pressure for being slim across socioeconomic strata contribute to the
      social stratification of body size among women in modern societies. Thinness is
      most valued by high SES women, following western standards of ideal body size.
      Aiming to understand the link between ideals of body size and SES, this
      qualitative study explored how 36 Chilean women construct their bodily ideals
      according to their social position. A purposive sample of women with different
      profiles with regard to educational attainment, nutritional status and body size
      (dis)satisfaction was defined, aiming to cover a diverse spectrum of bodily
      perceptions. Data were collected through semi-structured interviews and
      approached through a thematic and narrative analysis. Drawing on Bourdieu's
      concepts of habitus, field, capital and embodiment of the social context, this
      study explains how ideals of body size and appearance are strongly linked to
      class-dependent gender roles and social roles. The existing gender and class
      inequalities in the Chilean social structure have been literally embodied by
      these women through a 'gendered class habitus'. Compliance with the thin ideal
      confers women different degrees of power according to their social position in
      different fields, such as in marriage and on the labour market, which turns
      thinness into an embodied form of capital. The societal dynamic behind obesity
      rates cannot be disregarded when approaching possible solutions. Promoting
      obesity-related lifestyle modification at an individual level might appear an
      over-simplistic and individualistic approach to a complex social issue. Context
      oriented interventions that take cultural constructions of gender and social
      class into account might yield better results in the long term, while advocating
      for a more equitable society and social justice as a public health concern.

PMID- 29459283
TI  - Insula mediates heartbeat related effects on visual consciousness.
AB  - Interoceptive signals, such as the heartbeat, are processed in a network of brain
      regions including the insular cortex. Recent studies have shown that such signals
      modulate perceptual and cognitive processing, and that they impact visual
      awareness. For example, visual stimuli presented synchronously to the heartbeat
      take longer to enter visual awareness than the same stimuli presented
      asynchronously to the heartbeat, and this is reflected in anterior insular
      activation. This finding demonstrated a link between the processing of
      interoceptive and exteroceptive signals as well as visual awareness in the
      insular cortex. The advantage for visual stimuli which are asynchronous to the
      heartbeat to enter visual consciousness may indicate a role for the anterior
      insula in the suppression of the sensory consequences of cardiac signals. Here,
      we present data from the detailed investigation of two patients with insular
      lesions (as well as four patients with non-insular lesions and healthy age
      matched controls) indicating that a lesion of the anterior insular cortex, but
      not of other regions, abolished this cardio-visual suppression effect. The
      present data provide causal evidence for the role of the anterior insula in the
      integration of internal interoceptive and external sensory signals for visual
      awareness.

PMID- 29459284
TI  - Prefrontal mediation of the reading network predicts intervention response in
      dyslexia.
AB  - A primary challenge facing the development of interventions for dyslexia is
      identifying effective predictors of intervention response. While behavioral
      literature has identified core cognitive characteristics of response, the
      distinction of reading versus executive cognitive contributions to response
      profiles remains unclear, due in part to the difficulty of segregating these
      constructs using behavioral outputs. In the current study we used functional
      neuroimaging to piece apart the mechanisms of how/whether executive and reading
      network relationships are predictive of intervention response. We found that
      readers who are responsive to intervention have more typical pre-intervention
      functional interactions between executive and reading systems compared to
      nonresponsive readers. These findings suggest that intervention response in
      dyslexia is influenced not only by domain-specific reading regions, but also by
      contributions from intervening domain-general networks. Our results make a
      significant gain in identifying predictive bio-markers of outcomes in dyslexia,
      and have important implications for the development of personalized clinical
      interventions.

PMID- 29459285
TI  - Evaluation of a rapid DNA process with the RapidHIT(r) ID system using a
      specialized cartridge for extracted and quantified human DNA.
AB  - The turn-around time of urgent crime scene DNA samples is often far longer than
      desired by law enforcement. Crime scene DNA sample processing involves both
      complex and routine processing steps. Simplification and integration of the
      routine steps would dramatically improve turn-around time and reduce the risk of
      operator contamination. Routine DNA extraction and quantitation is readily
      available. However, PCR amplification and electrophoretic analysis remain largely
      manual. Rapid DNA Analysis is a hands-free "swab in - profile out" process which
      consists of automated DNA extraction, amplification, separation, detection, and
      allele calling without human intervention. RapidHIT(r) 200 and RapidHIT ID are
      rapid DNA systems developed by IntegenX (Pleasanton, CA) and validated for the
      use of buccal swabs. A new generation of the RapidHIT sample cartridge for
      RapidHIT ID has been designed and tested which allows the loading of extracted
      and quantified DNA. RapidHIT EXT sample cartridge allows a user to generate a
      forensic DNA profile from less than 250 pg of extracted and quantified DNA in
      less than 90 min with less than one-minute hands-on time. Once the sample is
      loaded in the RapidHIT EXT sample cartridge, a DNA profile is produced after
      amplification, detection and automated data analysis. We report on sensitivity,
      reproducibility, concordance, DNA mixtures and carryover for EXT sample
      cartridges pre-loaded with GlobalFiler(r) Express and AmpFLSTR(r) NGM SElectTM
      Express, (Thermo Fisher Scientific, Waltham, MA) STR chemistries. Purified and
      quantified DNA from mock crime scene samples were used to demonstrate the utility
      of these cartridges in an established forensic laboratory.

PMID- 29459286
TI  - Effects of the inoculations using bacteria producing ACC deaminase on ethylene
      metabolism and growth of wheat grown under different soil water contents.
AB  - Crop growth and productivity are often impacted by the increased ethylene content
      induced by adverse environmental conditions such drought. Inoculations with
      bacteria producing ACC deaminase is considered as a potential biological approach
      to improve the growth and tolerance of stressed plants by lowering endogenous
      ethylene level. In this study, germinated wheat seeds were inoculated using three
      species of the rhizobacteria, which were isolated from the rhizosphere of wheat
      growing in dryland, and sown in pots. After three weeks, wheat seedlings were
      exposed to non-limiting water condition, medium drought and severe drought,
      respectively, for six weeks. The results showed that, irrespective of
      rhizobacterial inoculations, decreased soil water contents stimulated wheat
      ethylene metabolism, which was reflected by the significantly increased activity
      of ACC synthetase and ACC oxidase, besides an increased content of ACC both in
      the roots and leaves, and an enhanced capacity of leaves to release ethylene,
      concomitant with a significant decline in shoot and roots biomass. The
      inoculations of all three rhizobacterial species under each water condition
      reduced ACC content in wheat leaves, but effects of the inoculations on ACC
      synthase and ACC oxidase activity in the leaves and roots, ACC content in the
      roots, the capacity of leaves to release ethylene, and wheat growth varied with
      water conditions and bacterial species. Hence, both soil water conditions and
      rhizobacterial inoculations acted on all the processes of ethylene metabolism,
      with the former being dominant. The inoculations under non-limiting water
      condition and medium drought promoted shoot and root growth of wheat plants.

PMID- 29459287
TI  - Application of a diffusion model to measure ion leakage of resurrection plant
      leaves undergoing desiccation.
AB  - Haberlea rhodopensis is a chlorophyll-retaining resurrection plant, which can
      survive desiccation to air dry state under both low light and sunny environments.
      Maintaining the integrity of the membrane during dehydration of resurrection
      plants is extremely important. In the present study, the diffusion model was
      improved and used for a first time to evaluate the changes in ion leakage through
      different cellular compartments upon desiccation of H. rhodopensis and to clarify
      the reasons for significant increase of electrolyte leakage from dry leaves. The
      applied diffusion approach allowed us to distinguish the performance of plants
      subjected to dehydration and subsequent rehydration under different light
      intensities. Well-hydrated (control) shade plants had lower and slower
      electrolyte leakage compared to control sun plants as revealed by lower values of
      phase amplitudes, lower rate constants and ion concentration. In well-hydrated
      and moderately dehydrated plants (50% relative water content, RWC) ion efflux was
      mainly due to leakage from apoplast. The electrolyte leakage sharply increased in
      severely desiccated leaves (8% RWC) from both sun and shade plants mainly due to
      ion efflux from symplast. After 1 day of rehydration the electrolyte leakage was
      close to control values, indicating fast recovery of plants. We suggest that the
      enhanced leakage in air-dried leaves should not be considered as damage but
      rather as a survival mechanism based on a reversible modification in the
      structure of cell wall, plasma membrane and alterations in vacuolar system of the
      cells. However, further studies should be conducted to investigate the changes in
      cell wall/plasma membrane to support this conclusion.

PMID- 29459288
TI  - Stimulus sensing and signal processing in bacterial chemotaxis.
AB  - Motile bacteria use chemotaxis to migrate towards environments that are favorable
      for growth and survival. The signaling pathway that mediates this behavior is
      largely conserved among prokaryotes, with Escherichia coli chemotaxis system
      being one of the simplest and the best studied. At the core of this pathway are
      the arrays of clustered chemoreceptors that detect, amplify and integrate various
      stimuli. Recent work provided deeper understanding of spatial organization and
      signal processing by these clusters and uncovered the variety of sensory
      mechanisms used to detect environmental stimuli. Moreover, studies of bacteria
      with different lifestyles have led to new insights into the diversity and
      evolutionary conservation of the chemotaxis pathway, as well as the physiological
      relevance of chemotactic behavior in different environments.

PMID- 29459289
TI  - Adhesion and relaxation of a soft elastomer on surfaces with skin like roughness.
AB  - For designing new skin adhesives, the complex mechanical interaction of soft
      elastomers with surfaces of various roughnesses needs to be better understood. We
      systematically studied the effects of a wide set of roughness characteristics,
      film thickness, hold time and material relaxation on the adhesive behaviour of
      the silicone elastomer SSA 7-9800 (Dow Corning). As model surfaces, we used epoxy
      replicas obtained from substrates with roughness ranging from very smooth to skin
      like. Our results demonstrate that films of thin and intermediate thickness (60
      and 160 um) adhered best to a sub-micron rough surface, with a pull-off stress of
      about 50 kPa. Significant variations in pull-off stress and detachment mechanism
      with roughness and hold time were found. In contrast, 320 um thick films adhered
      with lower pull-off stress of about 17 kPa, but were less sensitive to roughness
      and hold time. It is demonstrated that the adhesion performance of the silicone
      films to rough surfaces can be tuned by tailoring the film thickness and contact
      time.

PMID- 29459290
TI  - Mechanical, bactericidal and osteogenic behaviours of hydrothermally synthesised
      TiO2 nanowire arrays.
AB  - The application of orthopaedic implants is associated with risks of bacterial
      infection and long-term antibiotic therapy. This problem has led to the study of
      implants with nano-textured surfaces as a method of inhibiting bacterial adhesion
      and reducing implant failure due to infection. In this research, various nano
      textured surfaces of TiO2 were synthesised using hydrothermal synthesis, by
      varying NaOH concentration, reaction time and reaction temperature. Their
      correlations to mechanical, morphological, bactericidal and osteogenic properties
      of the surfaces were investigated. It was found that high alkaline concentrations
      produced large nanowire mesh arrays, while short reaction time and low
      temperature produced comparatively smaller arrays. The highly dense morphology
      formed at higher NaOH concentrations has resulted in high elastic modulus and
      hardness values, compared to surfaces produced at lower NaOH concentrations.
      Viability tests of the TiO2 nanowire array against gram-positive Staphylococcus
      aureus cells showed a bactericidal efficiency of 54% and 33% after 3 and 18 h,
      respectively. This nano-textured surface produces an osteoblast cellular
      metabolic activity of 71% after 24 h, compared to 67% when exposed to a flat Ti
      control surface. This preliminary work demonstrates an excellent outcome in
      producing bactericidal surfaces that promoted metabolic activity of human
      osteoblast cells for potential use in orthopaedic implants.

PMID- 29459291
TI  - The visible-light photodegradation of nonylphenol in the presence of carbon-doped
      TiO2 with rutile/anatase ratio coated on GAC: Effect of parameters and
      degradation mechanism.

PMID- 29459293
TI  - Determining the most significant input parameters in models of subendocardial
      ischaemia and their effect on ST segment epicardial potential distributions.
AB  - There is considerable interest in simulating ischaemia in the ventricle and its
      effect on the electrocardiogram, because a better understanding of the connection
      between the two may lead to improvements in diagnosis of myocardial ischaemia. In
      this work we studied subendocardial ischaemia, in a simplified half-ellipsoidal
      bidomain model of a ventricle, and its effect on ST segment epicardial potential
      distributions (EPDs). We found that the EPD changed as the ischaemic depth
      increased, from a single minimum (min1) over the ischaemic region to a maximum
      (max) there, with min1 over the border of the region. Lastly, a second minimum
      (min2) developed on the opposite side of the ischaemic region, in addition to
      min1 and max. We replicated these results in a realistic ventricular model and
      showed that the min1 only case could be found for ischaemic depths of up to
      around 35% of the ventricular wall. In addition, we systematically examined the
      sensitivity of EPD parameters, such as the potentials and positions of min1, max
      and min2, to various inputs to the half-ellipsoidal model, such as fibre rotation
      angle, ischaemic depth and conductivities. We found that the EPD parameters were
      not sensitive to the blood or transverse bidomain conductivities and were most
      sensitive to either ischaemic depth and/or fibre rotation angle. This allowed us
      to conclude that the asynchronous development of the two minima might provide a
      way of distinguishing between low and high thickness subendocardial ischaemia,
      and that this method may well be valid despite variability in the population.

PMID- 29459292
TI  - Effect of off-plane bifurcation angles of primary bronchi on expiratory flows in
      the human trachea.
AB  - BACKGROUND: The human airway is exposed to the development of diverse flow
      patterns based on differences in its morphological/geometrical parameters across
      individuals. Although effects of the asymmetry between the right and left main
      bronchi on airway flows have been investigated in the past, there exists a
      paucity in terms of studies that focus on the role of stronger physiological
      asymmetric features, such as off-plane bifurcation angles of primary bronchi, in
      expiratory flows. METHOD: Computational fluid dynamic techniques have been used
      to demonstrate presence of Dean-type secondary flows and vortices in the
      bifurcation region. Formation of a distinctive pattern was observed corresponding
      to an increase in the off-plane branching angle. An experiment involving 3D
      printed airways and smoke was also performed to visualize flow patterns and
      verify simulation results. RESULTS: Good agreement was observed between
      computational and experimental results. Furthermore, it was revealed that the
      predicted wall shear stress distribution demonstrated significant changes (with a
      maximum shear stress increase of 30.7%) compared to conventional airway models
      that adopt symmetric bifurcation angles. The overall flow demonstrated a swerving
      motion, which was characterized by tracking the vortex cores (maximum accumulated
      radial movement of 72.6 degrees ) when they ascended towards the trachea inlet in
      off-plane airway models. CONCLUSIONS: It was confirmed that off-plane
      bifurcations in human trachea significantly alter the flow characteristics in
      expiratory flows. It is expected that the results of this study will provide
      useful information regarding increasingly advanced patient-specific treatments
      for respiratory diseases in the trachea.

PMID- 29459294
TI  - Bryophyllum pinnatum inhibits arginase II activity and prevents oxidative damage
      occasioned by carbon tetrachloride (CCl4) in rats.
AB  - Bryophyllum pinnatum (B. pinnatum) (Lam.) Oken is used in tropical Africa for the
      treatment of several diseases such as kidney and urinary disorders. This study
      was aimed to evaluate the effect of B. pinnatum on arginase II activity and its
      prevention against renal oxidative damage occasioned by CCl4 in rats. Rats were
      randomly divided into six groups; group I served as the control, group II served
      as carbon tetrachloride (CCl4) intoxicated group, group III-V animals were pre
      treated with silymarin (25 mg/kg body weight), 25 mg/kg body weight aqueous
      extracts of Bryophyllum pinnatum (AEBP) and 50 mg/kg body weight AEBP,
      respectively, for 14 days, followed by a single injection of CCl4. Group VI rats
      received AEBP only (50 mg/kg body weight). Results obtained revealed that CCl4
      intoxication significantly increased (p < 0.05) the levels of renal markers
      (serum urea, creatinine and arginase II) in rats when compared to the control
      group. Further, oxidative stress status appeared in CCl4-intoxicated rats, as
      evidence by significant elevation in malondialdehyde (MDA), with concomitant
      decrease in levels of functional sulfhydryl groups (SH), antioxidant enzymes and
      nitric oxide in rats' kidney. These adverse changes, due to CCl4 intoxication in
      rats, were however, prevented by pre-treatment with AEBP leaves (25 and 50 mg/kg
      body weight). The inhibition of arginase II, as well as increased antioxidant
      status by AEBP in CCl4-intoxicated rats suggests that B. pinnatum can protect
      kidney against CCl4-induced oxidative damage.

PMID- 29459295
TI  - The link between insulin resistance parameters and serum uric acid is mediated by
      adiposity.
AB  - BACKGROUND AND AIMS: Conflicting results suggest a link between serum uric acid
      (SUA), inflammation and glucose/insulin homeostasis; however, the role of
      adiposity in this relationship is not clear. Therefore, we evaluated the role of
      different adiposity factors, including central body mass index (BMI), peripheral
      waist circumference (WC), and visceral adiposity [visceral adipose tissue
      (apVAT)], on the association between SUA, inflammation and glucose/insulin
      homeostasis among US adults. METHODS: Data were extracted from the 2005-2010 US
      National Health and Nutrition Examination Surveys. Overall, 16,502 participants
      were included in the analysis (mean age = 47.1 years, 48.2% men). Analysis of co
      variance and "conceptus causal mediation" models were applied, while accounting
      for survey design. RESULTS: Corrected models showed that subjects with higher SUA
      levels have a less favorable profile of inflammation and glucose/insulin
      homeostasis parameters (all p < 0.001). We found that all our potential mediators
      (BMI, WC and apVAT) had an impact (to various extents) on the link between
      variables, including serum C-reactive protein (CRP), apolipoprotein-B (apoB),
      insulin resistance markers, 2-h blood glucose (2hG) and triglyceride, and fasting
      blood glucose (FBG) (TyG) index (all p < .001), while none of the potential
      mediators (BMI, apVAT, WC) had an impact on the link between FBG and glycated
      hemoglobin with SUA (all p > 0.05). We have found that all of our mediators
      partially mediated the link between inflammation and glucose/insulin homeostasis
      parameters and SUA. Of note, apVAT fully mediated the association between SUA and
      2hG. CONCLUSIONS: By applying advanced statistical techniques, we shed light on
      the complex link of SUA with inflammation and glucose/insulin homeostasis and
      quantify the role of adiposity factors in that link.

PMID- 29459296
TI  - Preservative effect of Asparagus racemosus: A novel additive for bioactive edible
      films for improved lipid oxidative stability and storage quality of meat
      products.
AB  - Asparagus racemosus was used as a bioactive ingredient for the development of a
      novel calcium alginate edible film with preservative potential for improved lipid
      oxidative stability and storage quality of meat products. Chevon sausages were
      used as a model system and were aerobically packaged in the edible films
      incorporated with A. racemosus viz. T0 (0.0%), T1 (1.0%) and T2 (2.0%) and were
      stored under refrigerated (4 +/- 1  degrees C) conditions. Products packaged in
      T1 and T2 edible films exhibited significantly (P < 0.05) lower values for TBARS
      (mg malonaldehyde/kg), microbial counts (cfu/g) and FFA (% oleic acid) indicating
      the bioactive properties of the developed films. Significantly (P < 0.05) higher
      sensory scores were recorded for the products packaged in T1 and T2 films. A.
      racemosus added antioxidant and antimicrobial properties to the developed films
      which improved the lipid oxidative stability and storage quality of the model
      meat product.

PMID- 29459297
TI  - Perceived naturalness and evoked disgust influence acceptance of cultured meat.
AB  - Cultured meat could be a more environment- and animal-friendly alternative to
      conventional meat. However, in addition to the technological challenges, the lack
      of consumer acceptance could be a major barrier to the introduction of cultured
      meat. Therefore, it seems wise to take into account consumer concerns at an early
      stage of product development. In this regard, we conducted two experiments that
      examined the impact of perceived naturalness and disgust on consumer acceptance
      of cultured meat. The results of Experiment 1 suggest the participants' low level
      of acceptance of cultured meat because it is perceived as unnatural. Moreover,
      informing participants about the production of cultured meat and its benefits has
      the paradoxical effect of increasing the acceptance of traditional meat.
      Experiment 2 shows that how cultured meat is described influences the
      participants' perception. Thus, it is important to explain cultured meat in a
      nontechnical way that emphasizes the final product, not the production method, to
      increase acceptance of this novel food.

PMID- 29459298
TI  - Association of single nucleotide polymorphisms in fat metabolism candidate genes
      with fatty acid profiles of muscle and subcutaneous fat in heavy pigs.
AB  - Dietary and organoleptic qualities of pork products are largely influenced by the
      profiles of fatty acids (FAs) of meat and fat. The objective of this work was to
      investigate the potential associations between FA profile in subcutaneous adipose
      (back fat and leg fat) and muscular (longissimus dorsi and biceps femoris)
      tissues in heavy pigs (n = 129, 9-month-old) with single nucleotide polymorphisms
      (SNPs) in six candidate genes involved in fat metabolism: Stearoyl-CoA desaturase
      (SCD), Diacylglycerol acyltransferase 1 and 2 (DGAT1 &DGAT2), Microsomal
      Triglyceride Transfer Protein (MTTP), Fatty Acid Synthase (FASN) and Heart- fatty
      acid binding protein (H-FABP). Preliminary results suggest a putative association
      between MTTP, DGAT2 and FASN and the FA content in both fat and meat, whereas
      between DGAT1, SCD and H-FABP the association was found in adipose tissue only.
      However, the effect of the analyzed genes, needs to be verified in a larger and
      better characterized pig population to support the hypothesized associations with
      FA content.

PMID- 29459299
TI  - Association of ultimate pH and stress-related blood variables in cattle.
AB  - The objective of this study was to investigate the relationship between ultimate
      pH (pHu) and stress-related blood variables. Of 50 cattle in total, blood samples
      from 6 cattle which exhibited high (>=6.10) pHu (dark-cutting) were collected,
      along with the same number of low pHu and intermediate pHu cattle (5.40-5.80;
      5.80-6.10, respectively) to determine the concentration of plasma cortisol,
      glucose, lactate, creatine kinase, lactate dehydrogenase, haptoglobin and serum
      amyloid A protein. Compared to cattle with low pHu, high pHu cattle showed higher
      plasma cortisol, glucose, lactate, creatine kinase and lactate dehydrogenase
      levels at exsanguination. But the concentration of haptoglobin and serum amyloid
      A protein showed no significant differences among three pH groups. These results
      imply that measuring plasma cortisol, glucose, lactate, creatine kinase, or
      lactate dehydrogenase levels at exsanguination may be useful to identify the dark
      cutting beef condition.

PMID- 29459300
TI  - Fatty acid composition of intramuscular fat and odour-active compounds of lamb
      commercialized in northern Spain.
AB  - Muscle fatty acid composition and odour-active compounds released during cooking
      were characterized in lamb chops (Longissimus thoracis et lumborum, n = 48)
      collected at retail level in northern Spain. Lamb samples were classified in two
      groups according to their 10 t/11 t-18:1 ratio: <=1 (10 t-non-shifted, n = 21)
      and >1 (10 t-shifted, n = 27). Higher n-3 polyunsaturated fatty acid, vaccenic
      (11 t-18:1) and rumenic acid (9c,11 t-18:2), and iso-branched chain fatty acid
      contents were found in non-shifted lamb samples while n-6 polyunsaturated fatty
      acid, internal methyl-branched chain fatty acid, and 10 t-18:1 contents were
      greater in shifted samples. Regardless the fatty acid profile differences between
      lamb sample groups, odour-active compound profile was very similar and mostly
      affected by the cooking conditions. Overall, the main odour-active compounds of
      cooked lamb were described as "green", "meaty", "roasted", and "fatty" being
      methyl pyrazine, methional, dimethyl pyrazine, and dimethyl trisulphide the main
      odour-active compounds. Aldehydes and alcohols were the most abundant volatiles
      in all samples, and they were mostly originated from the oxidation of unsaturated
      fatty acids during cooking.

PMID- 29459301
TI  - Effect of small molecules on the phase behavior and coacervation of aqueous
      solutions of poly(diallyldimethylammonium chloride) and poly(sodium 4-styrene
      sulfonate).
AB  - HYPOTHESIS: Complex coacervates are capable of easily partitioning solutes within
      them based on relative affinities of solute-water and solute-polyelectrolyte
      pairs, as the coacervate phase has low surface tension with water, facilitating
      the transport of small molecules into the coacervate phase. The uptake of small
      molecules is expected to influence the physicochemical properties of the complex
      coacervate, including the hydrophobicity within coacervate droplets, phase
      boundaries of coacervation and precipitation, solute uptake capacity, as well as
      the coacervate rheological properties. EXPERIMENTS: Phase behavior of aqueous
      solutions of poly(diallyldimethylammonium chloride) (PDAC) and poly(sodium 4
      styrene sulfonate) (SPS) was investigated in the presence of various
      concentrations of two different dyes, positively charged methylene blue (MB) or
      non-charged bromothymol blue (BtB), using turbidity measurements. These materials
      were characterized with UV-vis spectroscopy, zeta potential measurements,
      isothermal titration calorimetry (ITC), fluorescence spectroscopy, and dynamic
      rheological measurements. FINDINGS: The presence of MB or BtB accelerates the
      coacervation process due to the increased hydrophobicity within coacervates by
      the addition of MB or BtB. The encapsulated MB or BtB tends to reduce the ionic
      crosslink density in the PDAC-SPS coacervates, resulting in a much weaker
      interconnecting network of the PDAC-SPS coacervates.

PMID- 29459302
TI  - Microbial desalination cell with sulfonated sodium poly(ether ether ketone) as
      cation exchange membranes for enhancing power generation and salt reduction.
AB  - Microbial desalination cell (MDC) is a bioelectrochemical system capable of
      oxidizing organics, generating electricity, while reducing the salinity content
      of brine streams. As it is designed, anion and cation exchange membranes play an
      important role on the selective removal of ions from the desalination chamber. In
      this work, sulfonated sodium (Na+) poly(ether ether ketone) (SPEEK) cation
      exchange membranes (CEM) were tested in combination with quaternary ammonium
      chloride poly(2,6-dimethyl 1,4-phenylene oxide) (QAPPO) anion exchange membrane
      (AEM). Non-patterned and patterned (varying topographical features) CEMs were
      investigated and assessed in this work. The results were contrasted against a
      commercially available CEM. This work used real seawater from the Pacific Ocean
      in the desalination chamber. The results displayed a high desalination rate and
      power generation for all the membranes, with a maximum of 78.6+/-2.0% in salinity
      reduction and 235+/-7mWm-2 in power generation for the MDCs with the SPEEK CEM.
      Desalination rate and power generation achieved are higher with synthesized SPEEK
      membranes when compared with an available commercial CEM. An optimized
      combination of these types of membranes substantially improves the performances
      of MDC, making the system more suitable for real applications.

PMID- 29459303
TI  - The human skin as a sub-THz receiver - Does 5G pose a danger to it or not?
AB  - In the interaction of microwave radiation and human beings, the skin is
      traditionally considered as just an absorbing sponge stratum filled with water.
      In previous works, we showed that this view is flawed when we demonstrated that
      the coiled portion of the sweat duct in upper skin layer is regarded as a helical
      antenna in the sub-THz band. Experimentally we showed that the reflectance of the
      human skin in the sub-THz region depends on the intensity of perspiration, i.e.
      sweat duct's conductivity, and correlates with levels of human stress (physical,
      mental and emotional). Later on, we detected circular dichroism in the
      reflectance from the skin, a signature of the axial mode of a helical antenna.
      The full ramifications of what these findings represent in the human condition
      are still unclear. We also revealed correlation of electrocardiography (ECG)
      parameters to the sub-THz reflection coefficient of human skin. In a recent work,
      we developed a unique simulation tool of human skin, taking into account the skin
      multi-layer structure together with the helical segment of the sweat duct
      embedded in it. The presence of the sweat duct led to a high specific absorption
      rate (SAR) of the skin in extremely high frequency band. In this paper, we
      summarize the physical evidence for this phenomenon and consider its implication
      for the future exploitation of the electromagnetic spectrum by wireless
      communication. Starting from July 2016 the US Federal Communications Commission
      (FCC) has adopted new rules for wireless broadband operations above 24 GHz (5 G).
      This trend of exploitation is predicted to expand to higher frequencies in the
      sub-THz region. One must consider the implications of human immersion in the
      electromagnetic noise, caused by devices working at the very same frequencies as
      those, to which the sweat duct (as a helical antenna) is most attuned. We are
      raising a warning flag against the unrestricted use of sub-THz technologies for
      communication, before the possible consequences for public health are explored.

PMID- 29459304
TI  - Remediation of contaminated soils by enhanced nanoscale zero valent iron.
AB  - The use of nanoscale zero valent iron (nZVI) for in situ remediation of soil
      contamination caused by heavy metals and organic pollutants has drawn great
      concern, primarily owing to its potential for excellent activity, low cost and
      low toxicity. This reviews considers recent advances in our understanding of the
      role of nZVI and enhanced nZVI strategy in the remediation of heavy metals and
      persistent organic contaminants polluted soil. The performance, the migration and
      transformation of nZVI affected by the soil physical and chemical conditions are
      summarized. However, the addition of nZVI inevitably disturbs the soil ecosystem,
      thus the impacts of nZVI on soil organisms are discussed. In order to further
      investigate the remediation effect of nZVI, physical, chemical and biological
      method combination with nZVI was developed to enhance the performance of nZVI.
      From a high efficient and environmentally friendly perspective, biological method
      enhanced nZVI technology will be future research needs. Possible improvement of
      nZVI-based materials and potential areas for further applications in soil
      remediation are also proposed.

PMID- 29459306
TI  - Organochlorine concentrations in adipose tissue and survival in postmenopausal,
      Danish breast cancer patients.
AB  - BACKGROUND: Several studies have investigated an association between
      organochlorine-concentrations and breast cancer incidence, whereas few have
      investigated an association with breast cancer mortality. METHODS: We used Cox
      Proportional Hazards Models to estimate the association between adipose
      organochlorine-concentrations and mortality after breast cancer in a survivor
      cohort of 399 postmenopausal women. During a median follow-up of 16.1 years, 177
      women died; 119 from breast cancer. RESULTS: There was a general inverse
      association with PCB-concentration (e.g. SigmaPCBs: Mortality Rate Ratio (MRR)
      0.79, 95% confidence interval (CI) (0.64-0.98) per inter-quartile range (IQR)),
      and for all pesticides, except beta-Hexachlorocyclohexane, which was not
      associated with mortality (MRR 1.02(0.87-1.18) per IQR), and dieldrin, which was
      associated with a significantly increased risk of death (MRR 1.22(1.05-1.41) per
      IQR). We found an interaction with prognostic factors for all PCBs, confining the
      inverse association to those with adverse prognostic factors. Results for
      pesticides suggested a similar, but mostly non-significant interaction. Dieldrin
      diverged from the general picture by being associated with increased mortality
      across all strata. CONCLUSION: A higher concentration of PCBs and several
      organochlorine pesticides may be inversely associated with breast cancer
      mortality among women with adverse prognostic factors. Further studies are
      required to investigate if this is a causal association. Dieldrin was associated
      with a higher mortality, regardless of prognostic factors. IMPACT: This is the
      first study to investigate an association between organochlorine concentrations
      in adipose tissue and breast cancer mortality. A prominent finding is a strong
      interaction with prognostic factors. The unexpected direction of association for
      most organochlorines encourages further studies of the role of individual
      metabolism of the organochlorines and a potentially stronger effect of the
      metabolites on mortality.

PMID- 29459305
TI  - Ambient air pollution and semen quality.
AB  - BACKGROUND: Ambient air pollution is associated with systemic increases in
      oxidative stress, to which sperm are particularly sensitive. Although decrements
      in semen quality represent a key mechanism for impaired fecundability, prior
      research has not established a clear association between air pollution and semen
      quality. To address this, we evaluated the association between ambient air
      pollution and semen quality among men with moderate air pollution exposure.
      METHODS: Of 501 couples in the LIFE study, 467 male partners provided one or more
      semen samples. Average residential exposure to criteria air pollutants and fine
      particle constituents in the 72 days before ejaculation was estimated using
      modified Community Multiscale Air Quality models. Generalized estimating equation
      models estimated the association between air pollutants and semen quality
      parameters (volume, count, percent hypo-osmotic swollen, motility, sperm head,
      morphology and sperm chromatin parameters). Models adjusted for age, body mass
      index, smoking and season. RESULTS: Most associations between air pollutants and
      semen parameters were small. However, associations were observed for an
      interquartile increase in fine particulates <=2.5 um and decreased sperm head
      size, including -0.22 (95% CI -0.34, -0.11) um2 for area, -0.06 (95% CI -0.09, 
      0.03) um for length and -0.09 (95% CI -0.19, -0.06) um for perimeter. Fine
      particulates were also associated with 1.03 (95% CI 0.40, 1.66) greater percent
      sperm head with acrosome. CONCLUSIONS: Air pollution exposure was not associated
      with semen quality, except for sperm head parameters. Moderate levels of ambient
      air pollution may not be a major contributor to semen quality.

PMID- 29459307
TI  - The timeline of blood pressure changes and hemodynamic responses during an
      experimental noise exposure.
AB  - BACKGROUND: Noise exposure increases blood pressure and peripheral vascular
      resistance in both genders in an experimental setting, as previously reported by
      the authors. OBJECTIVES: The aim of this re-analysis was to present the minute-by
      minute timeline of blood pressure changes and hemodynamic events provoked by
      traffic noise in the young and healthy adults. METHODS: The experiment consisted
      of three 10-min phases: rest in quiet conditions before noise (Leq = 40 dBA),
      exposure to recorded road-traffic noise (Leq = 89 dBA), and rest in quiet
      conditions after noise (Leq = 40 dBA). Participants' blood pressure, heart rate,
      and hemodynamic parameters (cardiac index and total peripheral resistance index)
      were concurrently measured with a thoracic bioimpedance device. The raw beat-to
      beat data were collected from 112 participants, i.e., 82 women and 30 men, aged
      19-32 years. The timeline of events was created by splitting each experimental
      phase into ten one-minute intervals (30 intervals in total). Four statistical
      models were fitted to answer the six study questions what is happening from one
      minute to another during the experiment. RESULTS: Blood pressure decreased during
      quiet phase before noise, increased in the first minute of noise exposure and
      then decreased gradually toward the end of noise exposure, and continued to
      decline to baseline values after noise exposure. The cardiac index showed a
      gradual decrease throughout the experiment, whereas total vascular resistance
      increased steadily during and after noise exposure. CONCLUSIONS: The timeline of
      events in this 30-min experiment provides insight into the hemodynamic processes
      underlying the changes of blood pressure before, during and after noise exposure.

PMID- 29459308
TI  - Air pollution and emergency department visits for respiratory diseases: A multi
      city case crossover study.
AB  - Increasing evidence suggests that ambient air pollution is a major risk factor
      for both acute and chronic respiratory disease exacerbations and emergencies. The
      objective of this study was to determine the association between ambient air
      pollutants and emergency department (ED) visits for respiratory conditions in
      nine districts across the province of Ontario in Canada. Health, air pollutant
      (PM2.5, NO2, O3, and SO2), and meteorological data were retrieved from April 2004
      to December 2011. Respiratory diseases were categorized as: chronic obstructive
      pulmonary disease (COPD, including bronchiectasis) and acute upper respiratory
      diseases. A case-crossover design was used to test the associations between ED
      visits and ambient air pollutants, stratified by sex and season. For COPD among
      males, positive results were observed for NO2 with lags of 3-6 days, for PM2.5
      with lags 1-8, and for SO2 with lags of 4-8 days. For COPD among females,
      positive results were observed for O3 with lags 2-4 days, and for SO2 among lags
      of 3-6 days. For upper respiratory disease emergencies among males, positive
      results were observed for NO2 (lags 5-8 days), for O3, (lags 0-6 days), PM2.5
      (all lags), and SO2 (lag 8), and among females, positive results were observed
      for NO2 for lag 8 days, for O3, PM2.5 among all lags. Our study provides evidence
      of the associations between short-term exposure to air pollution and increased
      risk of ED visits for upper and lower respiratory diseases in an environment
      where air pollutant concentrations are relatively low.

PMID- 29459309
TI  - Success of mainstream partial nitritation/anammox demands integration of
      engineering, microbiome and modeling insights.
AB  - Twenty years ago, mainstream partial nitritation/anammox (PN/A) was conceptually
      proposed as pivotal for a more sustainable treatment of municipal wastewater. Its
      economic potential spurred research, yet practice awaits a comprehensive recipe
      for microbial resource management. Implementing mainstream PN/A requires
      transferable and operable ways to steer microbial competition as to meet
      discharge requirements on a year-round basis at satisfactory conversion rates. In
      essence, the competition for nitrogen, organic carbon and oxygen is grouped into
      'ON/OFF' (suppression/promotion) and 'IN/OUT' (wash-out/retention and seeding)
      strategies, selecting for desirable conversions and microbes. Some insights need
      mechanistic understanding, while empirical observations suffice elsewhere. The
      provided methodological R&D framework integrates insights in engineering,
      microbiome and modeling. Such synergism should catalyze the implementation of
      energy-positive sewage treatment.

PMID- 29459310
TI  - Regulation of vitamin D metabolism following disruption of the microbiota using
      broad spectrum antibiotics.
AB  - Vitamin D, 25hydroxyvitamin D (25D), and 24,25dihydroxyvitamin D (24,25D) were
      measured before and after broad spectrum antibiotic (Abx) treatment for 2 wks.
      Abx treatments increased 25D and 24,25D levels suggesting that the microbiota or
      Abx were altering vitamin D metabolism. Increased 25D, but not 24,25D, following
      Abx treatments were found to be dependent on toll like receptor signaling.
      Conversely, the effects of Abx on 24,25D levels required that the vitamin D
      receptor (VDR) be expressed in tissues outside of the hematopoietic system
      (kidney) and not the immune system. Fibroblast growth factor (FGF)23 increased
      following Abx treatment and the effect of Abx treatment on FGF23 (like the effect
      on 24,25D) was not present in VDR knockout (KO) mice. The Abx mediated increase
      in 24,25D was due to changes to the endocrine regulation of vitamin D metabolism.
      Conversely, 25D levels went up with Abx treatment of the VDR KO mice. Host
      sensing of microbial signals regulates the levels of 25D in the host.

PMID- 29459311
TI  - Effect of hyaluronic acid hydrogels containing astrocyte-derived extracellular
      matrix and/or V2a interneurons on histologic outcomes following spinal cord
      injury.
AB  - One reason for the lack of regeneration, and poor clinical outcomes, following
      central nervous system (CNS) injury is the formation of a glial scar that
      inhibits new axon growth. In addition to forming the glial scar, astrocytes have
      been shown to be important for spontaneous SCI recovery in rodents, suggesting
      some astrocyte populations are pro-regenerative, while others are inhibitory
      following injury. In this work, the effect of implanting hyaluronic acid (HA)
      hydrogels containing extracellular matrix (ECM) harvested from mouse embryonic
      stem cell (mESC)-derived astrocytes on histologic outcomes following SCI in rats
      was explored. In addition, the ability of HA hydrogels with and without ECM to
      support the transplantation of mESC-derived V2a interneurons was tested. The
      incorporation of ECM harvested from protoplasmic (grey matter) astrocytes, but
      not ECM harvested from fibrous (white matter) astrocytes, into hydrogels was
      found to reduce the size of the glial scar, increase axon penetration into the
      lesion, and reduce macrophage/microglia staining two weeks after implantation. HA
      hydrogels were also found to support transplantation of V2a interneurons and the
      presence of these cells caused an increase in neuronal processes both within the
      lesion and in the 500 MUm surrounding the lesion. Overall, protoplasmic mESC
      derived astrocyte ECM showed potential to treat CNS injury. In addition, ECM:HA
      hydrogels represent a novel scaffold with beneficial effects on histologic
      outcomes after SCI both with and without cells.

PMID- 29459312
TI  - Enhanced antimicrobial, anti-oxidant applications of green synthesized AgNPs- an
      acute chronic toxicity study of phenolic azo dyes & study of materials surface
      using X-ray photoelectron spectroscopy.
AB  - The drug resistant bacteria and textile contaminations of water cause different
      sever health problem throughout the world. To overcome this issue, new
      environmental benign materials and methods are needed. Plant metabolites directed
      synthesis of nanoparticles is considered eco-friendly and easy in synthesis.
      Therefore, it was explicit for the synthesis of AgNPs. The prepared AgNPs were
      evaluated for antibacterial, antioxidant, photo-catalytic and electrochemical
      degradation properties as well as toxicity of degradation products on aquatic
      life. X-Ray Photoelectron Spectroscopy (XPS) has been used for analyzing the
      surface chemistry of prepared AgNPs. The particle size determines the interaction
      of nanoparticles with pathogens. Both Gram positive and negative bacteria
      (Escherichia coli and Staphylococcus areous) are used to determine the anti
      microbial potency of the green synthesized AgNPs. The synthesized silver
      nanoparticles showed significant anti-bacterial applications against B. subtilus
      and S. aureus. The anti-oxidant applications of AgNPs also studied on comparison
      with vitamin C. The toxicity of the phenolic Azo dyes (PDA) has been studied
      against Fish, Daphnia and Green Algae. The electrode potential was studied in the
      electrochemical redox reaction of hydroxy phenol in aqueous media. Simple
      electrolyte was used to determine the current efficiency. For the stability of
      electrode multi cyclic voltammetry was also studied during redox reaction, which
      showed stability under the potential 0.4 to 0.2 V.

PMID- 29459313
TI  - Laser assisted anticancer activity of benzimidazole based metal organic
      nanoparticles.
AB  - Recent studies showed that the photothermal therapy can be effectively used for
      the targeted cancerous cells destruction. Hence, in the present study,
      benzimidazole based metal organic complex nanoparticles, dichloro cobalt(II) bis
      benzimidazole (Co-BMZ) and dichloro copper(II) bis-benzimidazole (Cu-BMZ), were
      synthesized by reprecipitation method and their anti-cancer activity by means of
      photothermal effect has been studied. Transmission electron microscopy analysis
      shows that the particle size of Cu-BMZ is ~100 nm and Co-BMZ is in the range
      between 100 and 400 nm. Zeta potential analysis ensures the stability of the
      synthesized nanoparticles. It is found that the nonlinear absorption of the
      nanoparticles increases with increase in laser power intensity. Phototoxicity of
      human lung cancer (A549) and the normal mouse embryonic fibroblast (NIH-3T3)
      cells was studied using a 650 nm laser. Even though both the cell lines were
      affected by laser irradiation, A549 cells show higher cell destruction and lower
      IC50 values than the normal cells. Docking studies were used to analyse the
      interaction site and the results showed that the Cu-BMZ molecules have higher
      dock score than the Co-BMZ molecules. The obtained results indicate that Cu-BMZ
      samples have lesser particle size, higher nonlinear absorption and higher
      interaction energy than the Co-BMZ samples.

PMID- 29459314
TI  - The desert wormwood (Artemisia herba-alba) - From Arabian folk medicine to a
      source of green and effective nanoinsecticides against mosquito vectors.
AB  - The development of eco-friendly and effective insecticides is crucial for public
      health worldwide. Herein, we focused on the desert wormwood (Artemisia herba
      alba), a plant widely used in Arabian traditional medicine, as a source of green
      nanoinsecticides against mosquito vectors, as well as growth inhibitors to be
      employed against microbial pathogens. Ag nanoparticles (AgNPs) fabricated with
      the A. herba-alba extract were tested on Indian and Saudi Arabian strains of
      Anopheles, Aedes and Culex mosquitoes. The chemical profile of the A. herba-alba
      extract was determined by LC-DAD-MS and 1H NMR studies. Then, AgNPs were studied
      using UV-vis spectroscopy, XRD, FTIR spectroscopy, TEM, and EDX analyses.
      Artemisia herba-alba-synthesized AgNPs showed high larvicidal toxicity against
      mosquitoes from both Indian and Saudi Arabian strains. LC50 of AgNPs against
      Indian strains was 9.76 MUg/ml for An. stephensi, 10.70 MUg/ml for Ae. aegypti
      and 11.43 MUg/ml for Cx. quinquefasciatus, whereas against Saudi Arabian strains
      it was 33.58 MUg/ml for Ae. aegypti and 38.06 MUg/ml for Cx. pipiens. In
      adulticidal experiments, A. herba-alba extract showed LC50 ranging from 293.02 to
      450 MUg/ml, while AgNP LC50 ranged from 8.22 to 27.39 MUg/ml. Further, low doses
      of the AgNPs inhibited the growth of selected microbial pathogens. Overall, A.
      herba-alba can be further considered as a source of phytochemicals, with special
      reference to saponins, for effective and prompt fabrication of AgNPs with
      relevant insecticidal and bactericidal activity against species of high public
      health importance.

PMID- 29459316
TI  - Teaching student nurses how to use electronic patient records through simulation:
      A case study.
AB  - Like any skill in nursing, preparing students for the changes in technology needs
      to be incorporated into the curriculum. Electronic Patient Records (EPR) are an
      example of technological innovation in health care. This article presents a case
      study of how one faculty of healthcare, working collaboratively with a web
      designer, created and implemented a simulation activity to enable student nurses
      to develop their skills in using EPRs. An evaluation study was undertaken into
      students' perceptions of undertaking the simulation activity and using EPRs in
      the simulation activity. Findings showed that students were positive about the
      simulation activity and using the EPR app in the simulation, and felt well
      prepared for using EPR in practice.

PMID- 29459315
TI  - Magnetic resonance elastography to estimate brain stiffness: Measurement
      reproducibility and its estimate in pseudotumor cerebri patients.
AB  - This study determines the reproducibility of magnetic resonance elastography
      (MRE) derived brain stiffness in normal volunteers and compares it against
      pseudotumor patients before and after lumbar puncture (LP). MRE was performed on
      10 normal volunteers for reproducibility and 14 pseudotumor patients before and
      after LP. During LP, opening and closing cerebrospinal fluid (CSF) pressures were
      recorded before and after removal of CSF and correlated to brain stiffness.
      Stiffness reproducibility was observed (r > 0.78; p < 0.008). Whole brain opening
      LP stiffness was significantly (p = 0.04) higher than normals, but no significant
      difference (p = 0.11) in closing LP measurements. No significant correlation was
      observed between opening and closing pressure and brain stiffness.

PMID- 29459317
TI  - A novel anammox process combined with vibration technology.
AB  - This study investigated a fixed bed anammox bioreactor that uses vibration
      techniques to treat synthetic inorganic wastewater. Continuous experiments
      indicated that the activity elevation period could be shorten to one third, when
      the nitrogen removal rate (NRR) reached 1 kg.N/m3.d with vibration. R2 achieved
      the maximum NRR of 3.3 kg.N/m3.d under the resonance state, which was 1.8 times
      higher than the control reactor. Analysis of vibration intensity suggested that
      anammox activity would be great improved with the increasing vibration. These
      results indicated that vibration played a key role in system performance.
      Furthermore, high-throughput sequencing showed that the reactor with the
      vibration had a higher proportion of anammox bacteria, which increased 7 times
      than the biofilm formation phase. Meanwhile, the proportion of Proteobacteria and
      Chloroflexi decreased by 37.1% and 7.78%, respectively. These results suggest
      that vibration could increase the anammox treatment performance and provide a
      better condition for the anammox bacteria.

PMID- 29459318
TI  - Improving cellulose nanofibrillation of waste wheat straw using the combined
      methods of prewashing, p-toluenesulfonic acid hydrolysis, disk grinding, and
      endoglucanase post-treatment.
AB  - Here we established a new approach for improving the cellulose nanofibrillation
      of high ash content waste wheat straw (WWS). The results were comprehensively
      elucidated from the ash removal, delignification, mechanical fibrillation and
      endoglucanase post-treatment. When water dosage was increased from 50 to 500
      times of the WWS weight, the ash content gradually decreased during prewashing
      process, which facilitated lignin solubilization in subsequent p-toluenesulfonic
      acid (p-TsOH) hydrolysis. Approximately 80% of lignin in prewashed WWS could be
      dissolved during acid hydrolysis to result in a relatively higher crystallinity
      of 59.1%. Compared with the lignocellulosic nanofibrils (LCNF) directly obtained
      using acid hydrolysis and disk grinding, prewashing-assisted acid hydrolyzed WWS
      was fibrillated into LCNF with smaller height of 57.0 nm. Mild endoglucanase post
      treatment could further produce less entangled LCNF with thinner diameters. In
      short, this study presented a promising and green pathway to achieve an efficient
      utilization of agricultural residue wastes to cellulose nanomaterials.

PMID- 29459319
TI  - Effects of hydrostatic pressure and supercritical carbon dioxide on the viability
      of Botryococcus braunii algae cells.
AB  - In bio-based industries, Botryococcus braunii is identified as a potential
      resource for production of hydrocarbons having a wide range of applications in
      chemical and biopolymer industries. For a sustainable production platform, the
      algae cultivation should be integrated with downstream processes. Ideally the
      algae are not harvested, but the product is isolated while cultivation and growth
      is continued especially if the doubling time is slow. Consequently, hydrocarbons
      can be extracted while keeping the algae viable. In this study, the effects of
      pressure on the viability of B. braunii cells were tested hydrostatically and
      under supercritical CO2 conditions. Viability was determined by light microscopy,
      methylene blue uptake and by re-cultivation of the algae after treatments to
      follow the growth. It was concluded that supercritical CO2 was lethal to the
      algae, whereas hydrostatic pressure treatments up to 150 bar have not affected
      cell viability and recultivation was successful.

PMID- 29459320
TI  - Succession of the functional microbial communities and the metabolic functions in
      maize straw composting process.
AB  - Illumina MiSeq sequencing and phylogenetic investigation of communities by
      reconstruction of unobserved states (PICRUSt) were applied to study the dynamic
      changes and effects of microbial community structures as well as the metabolic
      function of bacterial community in maize straw composting process. Results showed
      that humic acid contents in loosely combined humus (HA1) and stably combined
      humus (HA2) increased after composting and Staphylococcus, Cellulosimicrobium and
      Ochrobactrum possibly participated in the transformation of the process. The
      bacterial communities differed in different stages of the composting. Firmicutes,
      Proteobacteria, Bacteroidetes and Actinobacteria were reported the dominant phyla
      throughout the process and the relative abundance of the dominant phyla varied
      significantly (p < 0.05) over time. Moreover, the total phosphorus (TP) had the
      greatest influence on the microbial community structure among C/N ratio,
      available phosphorus (AP) and humic substances. Metabolism, cellular processes
      and environmental information processing might be the primary functions of
      microbial community during the composting.

PMID- 29459321
TI  - Bioengineering an electro-mechanically functional miniature ventricular heart
      chamber from human pluripotent stem cells.
AB  - Tissue engineers and stem cell biologists have made exciting progress toward
      creating simplified models of human heart muscles or aligned monolayers to help
      bridge a longstanding gap between experimental animals and clinical trials.
      However, no existing human in vitro systems provide the direct measures of
      cardiac performance as a pump. Here, we developed a next-generation in vitro
      biomimetic model of pumping human heart chamber, and demonstrated its capability
      for pharmaceutical testing. From human pluripotent stem cell (hPSC)-derived
      ventricular cardiomyocytes (hvCM) embedded in collagen-based extracellular matrix
      hydrogel, we engineered a three-dimensional (3D) electro-mechanically coupled,
      fluid-ejecting miniature human ventricle-like cardiac organoid chamber (hvCOC).
      Structural characterization showed organized sarcomeres with myofibrillar
      microstructures. Transcript and RNA-seq analyses revealed upregulation of key
      Ca2+-handling, ion channel, and cardiac-specific proteins in hvCOC compared to
      lower-order 2D and 3D cultures of the same constituent cells. Clinically
      important, physiologically complex contractile parameters such as ejection
      fraction, developed pressure, and stroke work, as well as electrophysiological
      properties including action potential and conduction velocity were measured:
      hvCOC displayed key molecular and physiological characteristics of the native
      ventricle, and showed expected mechanical and electrophysiological responses to a
      range of pharmacological interventions (including positive and negative
      inotropes). We conclude that such "human-heart-in-a-jar" technology could
      facilitate the drug discovery process by providing human-specific preclinical
      data during early stage drug development.

PMID- 29459322
TI  - Biofunctionalized aligned microgels provide 3D cell guidance to mimic complex
      tissue matrices.
AB  - Natural healing is based on highly orchestrated processes, in which the
      extracellular matrix plays a key role. To resemble the native cell environment,
      we introduce an artificial extracellular matrix (aECM) with the capability to
      template hierarchical and anisotropic structures in situ, allowing a minimally
      invasive application via injection. Synthetic, magnetically responsive, rod
      shaped microgels are locally aligned and fixed by a biocompatible surrounding
      hydrogel, creating a hybrid anisotropic hydrogel (Anisogel), of which the
      physical, mechanical, and chemical properties can be tailored. The microgels are
      rendered cell-adhesive with GRGDS and incorporated either inside a cell-adhesive
      fibrin or bioinert poly(ethylene glycol) hydrogel to strongly interact with
      fibroblasts. GRGDS-modified microgels inside a fibrin-based Anisogel enhance
      fibroblast alignment and lead to a reduction in fibronectin production,
      indicating successful replacement of structural proteins. In addition, YAP
      translocation to the nucleus increases with the concentration of microgels,
      indicating cellular sensing of the overall anisotropic mechanical properties of
      the Anisogel. For bioinert surrounding PEG hydrogels, GRGDS-microgels are
      required to support cell proliferation and fibronectin production. In contrast to
      fibroblasts, primary nerve growth is not significantly affected by the
      biomodification of the microgels. In conclusion, this approach opens new
      opportunities towards advanced and complex aECMs for tissue regeneration.

PMID- 29459323
TI  - RF-assisted gadofullerene nanoparticles induces rapid tumor vascular disruption
      by down-expression of tumor vascular endothelial cadherin.
AB  - The tumor vasculature with unique characteristics offers an attractive target for
      anti-cancer therapy. Herein, we put forward a novel antitumor therapeutic
      mechanism based on the gadofullerene nanocrystals (GFNCs), the agent we have
      previously shown to efficiently disrupt tumor vasculature by size-expansion with
      assistance of radiofrequency (RF). However, the tumor vascular disrupting
      mechanism of RF-assisted GFNCs treatment was not further studied. In the present
      work, a rapid tumor blood flow shutdown has been observed by the vascular
      perfusion imaging in vivo and vascular damages were evident 6 h after the RF
      assisted GFNCs treatment. Importantly, a significant down-expression of tumor
      vascular endothelial cadherin (VE-cadherin) treated by RF-assisted GFNCs was
      further investigated, which caused vascular collapse, blood flow shut-down and
      subsequent tumor hemorrhagic necrosis. These findings set forth a systematic
      mechanism on the superior anti-tumor efficiency by RF-assisted GFNCs treatment.

PMID- 29459324
TI  - Near-infrared rechargeable "optical battery" implant for irradiation-free
      photodynamic therapy.
AB  - As a minimal or noninvasive therapeutic method for tumors, photodynamic therapy
      (PDT) induced by the external laser irradiations has attracted great attentions.
      However, the UV-visible responsive property with low tissue penetration and
      photothermal effect from the prolonged irradiation impedes their further
      applications. Herein, a near-infrared (NIR) rechargeable "optical battery" for
      irradiation-free PDT is fabricated by embedding upconversion materials,
      persistent luminescence materials, photosensitizer into biocompatible
      polydimethylsiloxane. After 5 s quickly charged by 980-nm NIR laser, the PDT
      "optical battery" can generate green persistent luminescence and produce
      cytotoxic singlet oxygen for continuous irradiation-free PDT (~30 min) without
      external irradiation. Due to deep tissue penetration and discontinuous short
      exposure of NIR light charging source, the "optical battery" can still be charged
      to continuously generate singlet oxygen in deep tissue (~4 mm) with low
      photothermal effect. The PDT implant can be easily optimized in size and shape
      aiming at different nidus sites and achieved different functions by adding other
      functional components (e.g. CaO2 for oxygen envolving to overcome hypoxia tumor).
      The effective tumor proliferation inhibiting capability of this NIR rechargeable
      "optical battery" may give rise to next generation of intelligent stimuli
      responsive nanomedicine and noninvasive photo bio-stimulation research for future
      clinical applications.

PMID- 29459326
TI  - Motor output complexity in Parkinson's disease during quiet standing and walking:
      Analysis of short-term correlations using the entropic half-life.
AB  - Parkinson's disease (PD) is associated with alterations in motor outputs such as
      center of pressure (CoP) adjustments during quiet standing and foot kinematics
      during walking. Previous research suggests that the complexity of motor outputs
      reflects the number of control processes stabilizing a specific movement,
      providing a measure that is linked to the neurological control of the movement.
      The Entropic Half Life (EnHL) represents a new method for assessing motor output
      complexity. We hypothesized that there will be a lack of neuromuscular control
      pathways for PD patients, resulting in a decrease in motor output complexity. We
      computed the EnHL of CoP adjustments during quiet standing and foot kinematics
      during walking of 70 PD patients and 33 age-matched controls. Patients with PD
      showed longer EnHL values compared to controls, suggesting a tighter motor
      control. Excluding vision led to a decrease of EnHL of CoP in both groups. EnHL
      was correlated with spatio-temporal gait parameters. We compared EnHL with the
      pull test and the timed up-and-go test. No significant differences were present
      in the pull test, yet motor output complexity was correlated with the timed up
      and-go test. The results suggest a reduced complexity in motor outputs of PD
      patients affecting distinct motor functions.

PMID- 29459325
TI  - Discontinuous Schedule of Bevacizumab in Colorectal Cancer Induces Accelerated
      Tumor Growth and Phenotypic Changes.
AB  - Antiangiogenics administration in colorectal cancer patients seemed promising
      therapeutic approach. Inspite of early encouraging results, it however gave only
      modest clinical benefits. When AAG was administered with discontinuous schedule,
      the disease showed acceleration in certain cases. Though resistance to AAG has
      been extensively studied, it is not documented for discontinuous schedules. To
      simulate clinical situations, we subjected a patient-derived CRC subcutaneous
      xenograft in mice to three different protocols: 1) AAG (bevacizumab) treatment
      for 30 days (group A) (group B was the control), 2) bevacizumab treatment for 50
      days (group C) and bevacizumab for 30 days and 20 without treatment (group D),
      and 3) bevacizumab treatment for 70 days (group E) and 70 days treatment with a
      drug-break period between day 30 and 50 (group F). The tumor growth was
      monitored, and at sacrifice, the vascularity of tumors was measured and the
      proangiogenic factors quantified. Tumor phenotype was studied by quantifying
      cancer stem cells. Interrupting bevacizumab during treatment accelerated tumor
      growth and revascularization. A significant increase of proangiogenic factors was
      observed when therapy was stopped. On withdrawal of bevacizumab, as also after
      the drug-break period, the plasmatic VEGF increased significantly. Similarly, a
      notable increase of CSCs after the withdrawal and drug-break period of
      bevacizumab was observed (P<.01). The present study indicates that bevacizumab
      treatment needs to be maintained because discontinuous schedules tend to trigger
      tumor regrowth, and increase tumor resistance and CSC heterogeneity.

PMID- 29459327
TI  - Changes in tobacco consumption in cannabis dependent patients with schizophrenia
      versus non-psychiatric controls during 28-days of cannabis abstinence.
AB  - BACKGROUND: Tobacco and cannabis are highly co-morbid in the general population
      and in patients with schizophrenia. Given the putative causal mechanisms
      facilitating co-use, it is important to determine how cannabis cessation may
      influence concurrent tobacco use. Using a 28-day cannabis abstinence paradigm, we
      prospectively examined changes in tobacco consumption in patients with
      schizophrenia and controls with cannabis dependence and daily cigarette use.
      METHODS: Cannabis dependent patients with schizophrenia (n = 19) and controls (n
      = 20) completed the study with abstinence rates of 42% and 55%, respectively.
      Participants completed measures of substance use, withdrawal, and clinical
      symptoms weekly. Urine samples were collected twice weekly to biochemically
      verify abstinence. RESULTS: Patients reported a greater increase in cigarettes
      smoked per day (CPD) on Day 7 relative to baseline (2.97 cigarette increase for
      abstinent subgroup, p < .01) compared to controls (.06 cigarette increase for
      abstinent subgroup, p = .95). Initially, greater reductions in cannabis use
      related to greater increases in CPD relative to baseline in the patient subsample
      (simple slope = -2.31, p = .05), but by Day 28, CPD returned to baseline levels
      independent of cannabis use. CPD changes were unrelated to cannabis withdrawal.
      Results were similar for changes in caffeine consumption, but not for alcohol.
      CONCLUSIONS: Findings suggest transient tobacco substitution for cannabis in
      patients with schizophrenia. This provides further support for a strong
      association between cannabis and tobacco in schizophrenia. Future studies should
      focus on targeting underlying mechanisms that promote co-use to better address
      potential changes in concurrent substance use during treatment interventions.

PMID- 29459328
TI  - Risk of fentanyl-involved overdose among those with past year incarceration:
      Findings from a recent outbreak in 2014 and 2015.
AB  - Overdose is the leading cause of unintentional injury-related death. Rhode Island
      (RI) has the highest rate of illicit drug use nationally and the 5th highest
      overdose mortality rate. RI has experienced an outbreak of fentanyl-related
      overdoses. In incarcerated populations, risk of overdose is greatly elevated.
      However, little is known about fentanyl-related overdose post-release. In the
      current analyses, we identify changes in fentanyl-related fatal overdose among
      those who died in 2014 and 2015 who were incarcerated in the year before death.
      We linked data from the RI Office of the Medical Examiner with records from the
      RI Department of Corrections. We calculated risk ratios and 95% confidence
      intervals using log-binomial regression to compare risk of fentanyl-involved
      overdose death. We also compared median time to death since release, median
      sentence length, and median number of incarcerations in 2014 and 2015. Results
      indicate that the risk of dying of a fentanyl-related overdose increased (RR:
      1.99 (95% CI: 1.11-3.57, p = 0.014)) from 2014 to 2015 among those with past year
      incarceration. This study is one of the first to describe fentanyl-related fatal
      overdose among those with past year incarceration. In 2015 the median sentence
      was longer among those with a fentanyl-related overdose death and the median time
      from release to death among all who had past year incarceration extended past 90
      days. Access to medications for addiction treatment, overdose education, and
      naloxone should be available during community re-entry and extended beyond the
      early post-release period.

PMID- 29459329
TI  - Investigation of key factors in preparation of alpha sources by
      electrodeposition.
AB  - The electrodeposition for alpha source preparation, using several electrolyte
      solution-cathode material combinations, is investigated and evaluated. The
      investigated factors focused on the electrodeposition time, the applied current,
      electrolyte volume and anode-cathode distances for the conventional
      electrodeposition cell (with no external stirring or cooling system). The
      conditions (temperature and the solution pH) during the electrodeposition process
      were also studied and discussed. The optimized parameters for each system are
      provided, and evaluated for the usage in determination of actinides (uranium,
      plutonium, americium and curium radioisotopes) in various samples.

PMID- 29459330
TI  - Overview and evaluation of different nuclear level density models for the 123I
      radionuclide production.
AB  - The 123I radionuclide (T1/2 = 13.22 h, beta+ = 100%) is one of the most potent
      gamma emitters for nuclear medicine. In this study, the cyclotron production of
      this radionuclide via different nuclear reactions namely, the 121Sb(alpha,2n),
      122Te(d,n), 123Te(p,n), 124Te(p,2n), 124Xe(p,2n), 127I(p,5n) and 127I(d,6n) were
      investigated. The effect of the various phenomenological nuclear level density
      models such as Fermi gas model (FGM), Back-shifted Fermi gas model (BSFGM),
      Generalized superfluid model (GSM) and Enhanced generalized superfluid model
      (EGSM) moreover, the three microscopic level density models were evaluated for
      predicting of cross sections and production yield predictions. The SRIM code was
      used to obtain the target thickness. The 123I excitation function of reactions
      were calculated by using of the TALYS-1.8, EMPIRE-3.2 nuclear codes and with data
      which taken from TENDL-2015 database, and finally the theoretical calculations
      were compared with reported experimental measurements in which taken from EXFOR
      database.

PMID- 29459331
TI  - Sensitive, selective, disposable electrochemical dopamine sensor based on PEDOT
      modified laser scribed graphene.
AB  - The fabrication of a novel, and highly selective electrochemical sensor based on
      a poly(3,4-ethylenedioxythiophene) (PEDOT) modified laser scribed graphene (LSG),
      and detection of dopamine (DA) in the presence of ascorbic acid (AA) and uric
      acid (UA) is described. LSG electrodes were produced with a 3-dimensional macro
      porous network and large electrochemically-active surface area via direct laser
      writing on polyimide sheets. PEDOT was electrodeposited on the LSG electrode, and
      the physical properties of the obtained films were characterized by scanning
      electron microscopy (SEM) and energy dispersive X-ray diffraction microanalysis
      (EDAX). The modified electrodes were applied for the determination of DA in the
      presence of AA and UA using cyclic voltammetry (CV), and differential pulse
      voltammetry (DPV) techniques. The linear range for dopamine detection was found
      to be 1-150 uM with a sensitivity of 0.220 +/- 0.011 uA MUM-1 and a detection
      limit of 0.33 uM; superior values to those obtained without PEDOT. For the first
      time, PEDOT-modified LSG have been fabricated and assessed for high-performance
      dopamine sensing using cost-effective, disposable electrodes, with potential for
      development in further sensing applications.

PMID- 29459332
TI  - Distribution and ecological risk assessment of organic and inorganic pollutants
      in the sediments of the transnational Begej canal (Serbia-Romania).
AB  - This research is designed to determine the level and types of pollution in the
      highly contaminated sediments of the international Begej canal in Timis district,
      Romania and north-eastern Serbia. The cross-border canal stretch investigated is
      currently not navigable, but represents an important waterway between the Danube
      River in Serbia and the city of Timisoara. Surface sediments were monitored
      annually from 2008 to 2016 at 36 representative sampling locations, with a wide
      range of analyses, including eight heavy metals of long-term monitoring concern
      (Ni, Zn, Cd, Cr, Cu, Pb, As and Hg) and the 16 USEPA PAHs. The purpose of this
      study was to determine the diversity and impact of anthropogenic and natural
      sources of pollution at the pollution hot spots on the canal: at the Itebej lock
      (near the border with Romania) and downstream at the Klek lock. Sediment quality
      and ecological risk were assessed in order to determine pollutants of concern.
      Several multi-proxies were applied (e.g. geo-accumulation index (Igeo),
      ecological risk index (RI) and total benzo[a]pyrene equivalent (B[a]Peq)). To
      determine and predict trends, multivariate statistical methods (factor analysis
      of principal component analysis (PCA/FA)) were carried out on the organic and
      inorganic parameters analysed. In the near-border region, acute and significant
      ecological impacts were observed. The heavy metals Hg, Cr, Pb, Cu and Zn, and the
      carcinogenic PAH dibenzo[a,h]anthracene, were historically the most frequently
      detected harmful substances to biota in this and the wider Pannonia region. This
      is the first long-term study to quantify and derivate the most frequently
      detected harmful substances of concern for this and similar sites in the wider
      region, and is additionally supported by significant national and similar
      environmental data from previous studies in the region.

PMID- 29459333
TI  - Contamination status by persistent organic pollutants of the Atlantic spotted
      dolphin (Stenella frontalis) at the metapopulation level.
AB  - The Atlantic spotted dolphin (Stenella frontalis) is an endemic species of the
      tropical-temperate Atlantic Ocean with widespread distribution. Although this
      species has been the subject of a large number of studies throughout its range,
      it remains in the "data deficient" category of the International Union for
      Conservation of Nature (IUCN). Chemical pollution by persistent organic
      pollutants (POPs) has been listed as one of the major threats to this species,
      however, there is no information on a wide scale. Thus, the aim of the present
      study was to investigate the contamination status of spotted dolphins on the
      metapopulation level as well as determine spatial and temporal variations in POP
      concentrations and bio-accumulation. A total of 115 blubber samples collected
      from a large part of the Atlantic basin were analysed for PCBs, DDTs, PBDEs,
      chlordanes, HCB and mirex. Although PCBs and DDTs were the predominant compounds
      in all areas, inter-location differences in POP concentrations were observed.
      Dolphins found at Sao Paulo, southeastern coast of Brazil, had the highest PCB
      concentrations (median: 10.5 MUg/g lw) and Canary Islands dolphins had the
      highest DDT concentrations (median: 5.13 MUg/g lw). Differences in PCB patterns
      among locations were also observed. Dolphins from the Azores and Sao Paulo
      demonstrated a similar pattern, with relatively highly contributions of tetra-
      (6.8 and 5.2%, respectively) and penta-CBs (25.6 and 23.8%, respectively) and
      lower contributions of hepta-CBs (20.8 and 23.5%, respectively) in comparison to
      other areas. Moreover, the sex of the animals and the year in which sampling or
      capture occurred exerted an important influence on the majority of the POPs
      analysed. Comparisons with toxicity thresholds available in the literature reveal
      that the Sao Paulo and Canary Island dolphins are the most vulnerable populations
      and should be considered in future conservation and management programs for the
      Atlantic spotted dolphin.

PMID- 29459334
TI  - Improved rice residue burning emissions estimates: Accounting for practice
      specific emission factors in air pollution assessments of Vietnam.
AB  - In Southeast Asia and Vietnam, rice residues are routinely burned after the
      harvest to prepare fields for the next season. Specific to Vietnam, the two
      prevalent burning practices include: a). piling the residues after hand
      harvesting; b). burning the residues without piling, after machine harvesting. In
      this study, we synthesized field and laboratory studies from the literature on
      rice residue burning emission factors for PM2.5. We found significant differences
      in the resulting burning-practice specific emission factors, with 16.9 g kg-2(+/
      6.9) for pile burning and 8.8 g kg-2(+/-3.5) for non-pile burning. We calculated
      burning-practice specific emissions based on rice area data, region-specific fuel
      loading factors, combined emission factors, and estimates of burning from the
      literature. Our results for year 2015 estimate 180 Gg of PM2.5 result from the
      pile burning method and 130 Gg result from non-pile burning method, with the most
      likely current emission scenario of 150 Gg PM2.5 emissions for Vietnam. For
      comparison purposes, we calculated emissions using generalized agricultural
      emission factors employed in global biomass burning studies. These results
      estimate 80 Gg PM2.5, which is only 44% of the pile burning-based estimates,
      suggesting underestimation in previous studies. We compare our emissions to an
      existing all-combustion sources inventory, results show emissions account for 14
      18% of Vietnam's total PM2.5 depending on burning practice. Within the highly
      urbanized and cloud-covered Hanoi Capital region (HCR), we use rice area from
      Sentinel-1A to derive spatially-explicit emissions and indirectly estimate
      residue burning dates. Results from HYSPLIT back-trajectory analysis stratified
      by season show autumn has most emission trajectories originating in the North,
      while spring has most originating in the South, suggesting the latter may have
      bigger impact on air quality. From these results, we highlight locations where
      emission mitigation efforts could be focused and suggest measures for pollutant
      mitigation. Our study demonstrates the need to account for emissions variation
      due to different burning practices.

PMID- 29459335
TI  - Evidence of niche partitioning among bacteria living on plastics, organic
      particles and surrounding seawaters.
AB  - Plastic pollution is widespread in ocean ecosystems worldwide, but it is unknown
      if plastic offers a unique habitat for bacteria compared to communities in the
      water column and attached to naturally-occurring organic particles. The large set
      of samples taken during the Tara-Mediterranean expedition revealed for the first
      time a clear niche partitioning between free-living (FL), organic particle
      attached (PA) and the recently introduced plastic marine debris (PMD). Bacterial
      counts in PMD presented higher cell enrichment factors than generally observed
      for PA fraction, when compared to FL bacteria in the surrounding waters.
      Taxonomic diversity was also higher in the PMD communities, where higher evenness
      indicated a favorable environment for a very large number of species.
      Cyanobacteria were particularly overrepresented in PMD, together with essential
      functions for biofilm formation and maturation. The community distinction between
      the three habitats was consistent across the large-scale sampling in the Western
      Mediterranean basin. 'Plastic specific bacteria' recovered only on the PMD
      represented half of the OTUs, thus forming a distinct habitat that should be
      further considered for understanding microbial biodiversity in changing marine
      ecosystems.

PMID- 29459336
TI  - Building a collective memory: the case for collective forgetting.
AB  - The shared reality of a community rests in part on the collective memories held
      by members of that community. Surprisingly, psychologists have only recently
      begun to study collective memories, an area of interest in the social sciences
      for several decades. The present paper adopts the perspective that remembering is
      often an act of communication. One consequence of communicative acts of
      remembering is that speaker and listeners can come to share the same memories,
      thereby providing a foundation on which to build a collective memory. Another
      consequence is that the selectivity of communicative acts of remembering can
      induce collective selective forgetting, clearly one component of any collective
      memory. The phenomenon of retrieval-induced forgetting is discussed in the
      context of dyadic conversational exchanges of unrelated individuals and
      conversational exchanges between ingroup and outgroup members. In addition, the
      paper reviews work demonstrating that what occurs at the dyadic level can shape
      global outcomes of complex social networks, including convergence of memories
      across a network. The bottom-up approach described in this paper can help us
      understand how individual memories can come to be shared across a community.

PMID- 29459337
TI  - Abundance of ammonia-oxidizing bacteria and archaea under different ventilation
      strategies during cattle manure composting.
AB  - Composting of cattle manure was conducted under four ventilation strategies,
      i.e., no-aeration (A-00), continuous aeration (B-44), non-aeration for 14 d and
      then aeration for 42 d (C-04), aeration for 14 d and then no-aeration for 42 d (D
      40). Physicochemical parameters and potential ammonia oxidation (PAO) indicated
      that continuous and intermittent ventilation provide favourable conditions for
      ammonia-oxidizing bacteria (AOB) and archaea (AOA) to oxidize ammonia.
      Quantitative PCR (qPCR) analysis showed AOB amoA gene abundance of all treatments
      on every sampling day ranged from 2.25 * 105 to 2.76 * 109copies/g, was
      significantly lower than that of archaeal amoA gene from 2.71 * 108 to 9.05 *
      1011copies/g. There was also a significantly positive relationship between PAO
      rates and AOB (r2 >= 0.066, p < 0.05) and AOA (r2 >= 0.300, p < 0.05) abundance.
      These data suggested that ammonia oxidation is driven by both AOA and AOB in
      cattle manure composting.

PMID- 29459338
TI  - Strategies for the sustainable management of orange peel waste through anaerobic
      digestion.
AB  - The processing of oranges is a major industry worldwide and leads to the
      production of large amounts of orange peel waste (OPW). Energy production through
      anaerobic digestion of OPW is a promising option; however, the high content of
      essential oil, mainly composed of d-limonene, a well-known antioxidant, can cause
      the inhibition of the biological activity. In this paper, different pretreatment
      methods were tested (e.g. ensiling, aeration, thermal and alkaline treatments) to
      optimize the anaerobic digestion of OPW focusing on d-limonene removal. The raw
      and pretreated substrates were characterized and their biochemical methane
      production was measured. The results demonstrated the ability of some of the
      treatments to reduce d-limonene content up to 80%. A relatively high biomethane
      potential production of OPW (up to about 500 NmL CH4 g-1VS) was measured. The
      importance of the acclimation of inoculum and the risk connected to the
      accumulation of inhibiting substances in the reactor is discussed.

PMID- 29459339
TI  - Estimating water user demand for certification of forest watershed services.
AB  - Eco-certification is one solution to the common problem of verification of
      delivery of services in payment for ecosystem services (PES) schemes.
      Certification incurs costs, which may limit uptake, so it should be able to
      benefit users of certified services for it succeeds. In part to inform a project
      targeting expansion of the Forest Stewardship Council's forest management
      certification to include ecosystem services, we tested market demand for a
      potential certification scheme for watershed services. Using choice experiments
      among end-users of water subject to an existing PES scheme in Lombok, Indonesia,
      we assessed potential business values of certification. Our results suggested
      that preferred business values included credible information disclosure on
      improved water quality, reduced flood risk, environmental safeguards, and/or
      social safeguards of the upstream forests. These preferences indicate potential
      demand for a certification of forest watershed services designed to provide such
      information to end users.

PMID- 29459340
TI  - Wet air oxidation of cresylic spent caustic - A model compound study over
      graphene oxide (GO) and ruthenium/GO catalysts.
AB  - Wet air oxidation (WAO) is a candidate technique for the effective treatment of
      spent caustic wastewater. In this work, cresols were chosen as model compounds to
      represent cresylic spent caustic wash. Graphene oxide (GO) is a promising
      catalyst as well as support for the wet oxidation process, due to its unique
      structure and properties. For the first time, GO and ruthenium supported on
      graphene oxide (Ru/GO) were employed for WAO of cresylic isomers. The aforesaid
      materials were synthesized by modified Hummer's method and characterized using
      scanning electron microscopy (SEM), field emission scanning electron microscopy
      (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT
      IR) spectroscopy, X-ray diffraction (XRD) and Brunauer-Emmett-Teller (BET)
      analysis. The performance of the investigated materials for WAO of cresols was
      studied in a slurry reactor. The best reaction conditions for GO were 175 
      degrees C and 0.69 MPa O2 pressure. Total organic carbon (TOC) degradation
      achieved at these conditions was 54.9, 48.9 and 61.2% for o-cresol, m-cresol and
      p-cresol, respectively. The amount of TOC degradation obtained by using Ru/GO at
      the same reaction conditions was 66.4, 53.4 and 73.9% for o-cresol, m-cresol and
      p-cresol, respectively. It was found that the order of reactivity for cresols was
      p-cresol > o-cresol > m-cresol. Finally, kinetics of TOC destruction during CWAO
      of p-cresol over GO was described using a two-step power law model.

PMID- 29459341
TI  - The knowledge, experience and attitudes of recipients of repetitive transcranial
      magnetic stimulation: A study from North India.

PMID- 29459342
TI  - Hemoglobin thresholds and red blood cell transfusion in adult patients with
      moderate or severe traumatic brain injuries: A retrospective cohort study.
AB  - PURPOSE: We aimed to evaluate the association between transfusion practices and
      clinical outcomes in patients with traumatic brain injury. MATERIAL AND METHODS:
      We conducted a retrospective cohort study of adult patients with moderate or
      severe traumatic brain injury admitted to the intensive care unit (ICU) of a
      level I trauma center between 2009 and 2013. The associations between hemoglobin
      (Hb) level, red blood cell (RBC) transfusion and clinical outcomes were estimated
      using robust Poisson models and proportional hazard models with time-dependent
      variables, adjusted for confounders. RESULTS: We included 215 patients. Sixty-six
      patients (30.7%) were transfused during ICU stay. The median pre-transfusion Hb
      among transfused patients was 81g/L (IQR 67-100), while median nadir Hb among non
      transfused patients was 110g/L (IQR 93-123). Poor outcomes were significantly
      more frequent in patients who were transfused (mortality risk ratio [RR]: 2.15
      [95% CI 1.37-3.38] and hazard ratio: 3.06 [95% CI 1.57-5.97]; neurological
      complications RR: 3.40 [95% CI 1.35-8.56]; trauma complications RR: 1.65 [95% CI
      1.31-2.08]; ICU length of stay geometric mean ratio: 1.42 [95% CI 1.06-1.92]).
      CONCLUSIONS: During ICU stay, transfused patients tended to have lower Hb levels
      and worse outcomes than patients who did not receive RBCs, after adjustment for
      confounders.

PMID- 29459343
TI  - A quasi-optical and corrugated waveguide microwave transmission system for
      simultaneous dynamic nuclear polarization NMR on two separate 14.1 T
      spectrometers.
AB  - Nuclear magnetic resonance (NMR) is an intrinsically insensitive technique, with
      Boltzmann distributions of nuclear spin states on the order of parts per million
      in conventional magnetic fields. To overcome this limitation, dynamic nuclear
      polarization (DNP) can be used to gain up to three orders of magnitude in signal
      enhancement, which can decrease experimental time by up to six orders of
      magnitude. In DNP experiments, nuclear spin polarization is enhanced by
      transferring the relatively larger electron polarization to NMR active nuclei via
      microwave irradiation. Here, we describe the design and performance of a quasi
      optical system enabling the use of a single 395 GHz gyrotron microwave source to
      simultaneously perform DNP experiments on two different 14.1 T (1H 600 MHz) NMR
      spectrometers: one configured for magic angle spinning (MAS) solid state NMR; the
      other configured for solution state NMR experiments. In particular, we describe
      how the high power microwave beam is split, transmitted, and manipulated between
      the two spectrometers. A 13C enhancement of 128 is achieved via the cross effect
      for alanine, using the nitroxide biradical AMUPol, under MAS-DNP conditions at
      110 K, while a 31P enhancement of 160 is achieved via the Overhauser effect for
      triphenylphosphine using the monoradical BDPA under solution NMR conditions at
      room temperature. The latter result is the first demonstration of Overhauser DNP
      in the solution state at a field of 14.1 T (1H 600 MHz). Moreover these results
      have been produced with large sample volumes (~100 uL, i.e. 3 mm diameter NMR
      tubes).

PMID- 29459344
TI  - Low level of serum HDL-cholesterol with increased sIL-2R predicts a poor clinical
      outcome for patients with malignant lymphoma and adult T-cell leukemia-lymphoma.
AB  - Low concentrations of high-density lipoprotein cholesterol (HDL-C) have been
      reported in patients with hematological malignancies. However, the proof of
      decreased HDL-C in hematological malignancies and its association with clinical
      outcomes remain unclear. We analyzed 140 Japanese patients with malignant
      lymphoma (ML) and adult T-cell leukemia-lymphoma (ATLL). HDL-C, LDL-C and soluble
      interleukin-2 receptor (sIL-2R) were measured. Treatment decisions were
      determined with established protocols. HDL-C was 0.98 +/- 0.45 mmol/l in patients
      and 1.51 +/- 0.35 mmol/l in controls (P < 0.001). LDL-C was lower in patients
      than in controls (2.76 +/- 0.96, 3.16 +/- 0.76 mmol/l, respectively, P < 0.001).
      HDL-C was the lowest in ATLL (0.81 +/- 0.37 mmol/l), modest in non-Hodgkin
      lymphoma (1.09 +/- 0.42 mmol/l) and the highest in Hodgkin's disease (1.14 +/-
      0.68 mmol/l), (P = 0.0019). Inverse correlation was found between HDL-C and sIL
      2R (r = -0.6584, P < 0.001). Categorized patients into 3 subgroups according to
      HDL-C (<0.52, 0.52-1.02 and >=1.03 mmol/l), sIL-2R were the highest (median,
      36,675; IQR, 17,180-92,600 U/mL) in patients with HDL-C < 0.52 mmol/l, modest
      (2386, 1324-8340) in HDL-C 0.52-1.02 mmol/l and the lowest (761, 450-1596) in HDL
      C >= 1.03 mmol/l (P < 0.001). In Cox regression model, the lowest HDL-C levels,
      <0.52 mmol/l, were associated with poorer clinical outcome and the hazard ratio
      was 5.73 (95%CI, 3.09-10.50; P < 0.001). In Kaplan-Meier analysis according to
      HDL-C tertiles (<0.78, 0.78-1.10 and >=1.11 mmol/l), patients with lowest HDL-C
      tertile showed inferior overall survival with a median follow-up of 23 months (P
      < 0.001). We concluded that cytokine-induced low levels of HDL-C in patients with
      ML and ATLL has independent prognostic significance, and suggesting an early
      indicator of poorer outcome.

PMID- 29459346
TI  - Predictors of retinal atrophy in multiple sclerosis: A longitudinal study using
      spectral domain optical coherence tomography with segmentation analysis.
AB  - BACKGROUND: Multiple sclerosis is an inflammatory demyelinating disease
      characterized by progressive axonal loss affecting mainly the inner retinal
      layers. Optical coherence tomography (OCT) provides in-vivo quantification of the
      retinal layers and allows measuring progressive retinal changes. Our objective
      was to assess the longitudinal changes in the retina using spectral domain OCT
      (SDOCT) and to identify independent predictors affecting retinal thinning in MS
      patients. METHODS: A prospective study in a tertiary care MS center was conducted
      to study the longitudinal retinal changes in MS patients. All subjects underwent
      baseline and follow up OCT assessment with segmentation analysis. Regression
      analysis was performed to assess clinical factors (age, sex, disease duration,
      history of optic neuritis before baseline, non-ocular clinical relapses) and MRI
      disease activity during the follow-up period. RESULTS: The study included 102 MS
      patients with a mean follow-up duration of 3.9 +/- SD years. At the last follow
      up assessments, there were significant thinning of the average macular thickness
      (AMT) (p < .001), macular nerve fiber layer (MRNFL) (p < .001), ganglion cell
      inner plexiform layer (GCIPL) (p < .001), and the peripapillary nerve fiber layer
      (PRNFL) (p < .001), compared to baseline. Early disease duration up to 10 years
      was associated with thinning of AMT, PRNFL, and GCIPL, while longer disease
      duration (> 15 years) was associated with only GCIPL thinning. Prior optic
      neuritis was predictive of more thinning of PRNFL (p = < .01), while MRI activity
      and female gender were significantly associated with more MRNFL thinning (p = <
      .01). CONCLUSION: MS is associated with longitudinal thinning affecting AMT inner
      retinal layers (MRNFL, GCIPL, PRNFL). Early disease duration, female gender, MRI
      activity, and prior optic neuritis were predictive of faster rate of neuro-axonal
      loss. This may have implications in the design of future therapeutic trials.

PMID- 29459345
TI  - Melanoma exosomes promote mixed M1 and M2 macrophage polarization.
AB  - Macrophages are key participants in melanoma growth and survival. In general,
      macrophages can be classified as M1 or M2 activation phenotypes. Increasing
      evidence demonstrates that melanoma exosomes also facilitate tumor survival and
      metastasis. However, the role of melanoma exosomes in directly influencing
      macrophage function is poorly understood. Herein, we investigated the hypothesis
      that natural melanoma exosomes might directly influence macrophage polarization.
      To explore this hypothesis, ELISA, RT-qPCR, and macrophage functional studies
      were performed in vitro using an established source of melanoma exosomes (B16
      F10). ELISA results for melanoma exosome induction of common M1 and M2 cytokines
      in RAW 264.7 macrophages, revealed that melanoma exosomes do not polarize
      macrophages exclusively in the M1 or M2 direction. Melanoma exosomes induced the
      M1 and M2 representative cytokines TNF-alpha and IL-10 respectively. Further
      assessment, using an RT-qPCR array with RAW 264.7 and primary macrophages,
      confirmed and extended the ELISA findings. Upregulation of markers common to both
      M1 and M2 polarization phenotypes included CCL22, IL-12B, IL-1beta, IL-6, i-NOS,
      and TNF-alpha. The M2 cytokine TGF-beta was upregulated in primary but not RAW
      264.7 macrophages. Pro-tumor functions have been attributed to each of these
      markers. Macrophage functional assays demonstrated a trend toward increased i-NOS
      (M1) to arginase (M2) activity. Collectively, the results provide the first
      evidence that melanoma exosomes can induce a mixed M1 and M2 pro-tumor macrophage
      activation phenotype.

PMID- 29459347
TI  - Rare device landing zone ruptures after transcatheter aortic valve implantation
      (TAVI).

PMID- 29459348
TI  - Effects of smoking and alcohol consumption on lipid profile in male adults in
      northwest rural China.
AB  - OBJECTIVES: To determine the individual and combined influences of smoking and
      alcohol consumption on lipid profile in male adults in northwest rural China.
      DESIGN: Cross-sectional study. METHODS: In total, 4614 subjects were enrolled in
      the cross-sectional study, performed between 2008 and 2012. The present study
      examined males aged >=18 years from northwest rural China (n = 707). Data on
      current smoking and drinking status were collected. Logistic regression was used
      to estimate the individual and combined influences of smoking and alcohol
      consumption on lipid profile. Age, ethnic group, educational background, smoking
      (or alcohol consumption), waist circumference, body mass index, blood pressure
      and fasting blood glucose were adjusted as confounders. RESULTS: Total
      cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio,
      triglycerides (TG)/HDL-C ratio, low-density lipoprotein cholesterol (LDL-C)/HDL-C
      ratio and visceral adiposity index (VAI) were significantly higher in smokers
      than in non-smokers, whereas HDL-C was lower in smokers. TG/HDL-C ratio, LDL
      C/HDL-C ratio, TG, lipid accumulation product and VAI were significantly higher
      in drinkers than non-drinkers. After adjustment for confounders, significant
      relationships were observed between smoking status and any dyslipidemia, low HDL
      C and high VAI (odds ratios [ORs]: 2.53 [95% confidence interval {CI}: 1.25
      5.15], 6.13 [95% CI: 2.84-13.25] and 4.39 [95% CI: 2.02-9.54], respectively). The
      OR for any dyslipidaemia was 1.94 (95% CI: 1.09-3.48) for subjects who smoke and
      drank alcohol compared with subjects who did not smoke or drink alcohol.
      CONCLUSIONS: Abnormalities in lipid profile are correlated with smoking and
      alcohol consumption, which calls for intervention strategies to prevent
      dyslipidaemia and control risk factors for cardiovascular disease.

PMID- 29459349
TI  - Spatial distribution of bisphenol S in surface water and human serum from Yangtze
      River watershed, China: Implications for exposure through drinking water.
AB  - Bisphenol S (BPS) is an emerging environmental contaminant. The occurrence of
      this compound in humans and the environment is not well described. In this study,
      120 surface water samples and 240 human serum samples were collected along the
      Yangtze River in 2015 for the determination of the occurrence of BPS. Surface
      water and human serum samples were extracted by solid phase extraction and liquid
      liquid extraction, respectively, and analyzed by ultra-high performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS). BPS was detected in all
      river water samples at concentrations that ranged from 0.18 to 14.9 ng/L (median:
      0.98 ng/L), with higher concentrations in spring than summer. The median
      estimated daily intake (EDI) of BPS through water ingestion by infants in spring
      and summer was 0.12 and 0.06 ng/kg body weight (bw)/day, respectively. BPS was
      detected in human serum with the highest concentrations in samples from Nanjing
      (median: 0.65 ng/mL, maximum: 169 ng/mL) among the four cities studied. No
      significant gender related difference in BPS concentrations was observed in human
      sera, while higher concentrations were found in younger individuals than elderly.
      The EDI of BPS calculated based on serum concentrations of adults in Nanjing was
      22.8 ng/kg bw/day. Ingestion of water accounted for <1% of the total BPS intake
      by the Chinese population. This is the first report of the occurrence of BPS in
      water from the Yangtze River and human serum from several cities located along
      this river in China.

PMID- 29459350
TI  - PBDEs and Dechlorane Plus in the environment of Guiyu, Southeast China: A
      historical location for E-waste recycling (2004, 2014).
AB  - Polybrominated diphenyl ethers (PBDEs, tri-to hepta-BDEs) and Dechlorane Plus
      (DP) in multiple samples (soil, sediment, road dust, and PM2.5 particles) in
      historical locations of our previous work in Guiyu (electronic-waste recycling
      town) in southeastern China were investigated in 2014. Ten years later, PBDEs and
      DP were detected in 100% of the samples. ?3-7PBDEs were still relatively great,
      ranging from 1.2 * 101 to 2.1 * 103 ng/g dry weight (dw) in soil, 2.1 to 3.2 *
      103 ng/g dw in sediment, 1.0 * 101 to 1.1 * 104 ng/g dw in road dust, which were
      a little less than or close to those measured in 2004. However, ?3-7PBDEs in
      PM2.5 (5.0 * 102 to 8.4 * 102 pg/m3) were significantly lower in 2014. BDE-47, 
      99, -153, and -183 were predominant congeners, which were also predominant PBDEs
      reported in Guiyu (2006-2008). Greater proportions of lesser-brominated BDEs were
      predominant in PM2.5 than other samples. DP was detected in 100% of the samples
      collected with high levels. Total syn-DP and anti-DP concentrations were 3.8 to
      2.1 * 103 ng/g dw in soil, 1.1 * 103 to 7.2 * 103 ng/g dw in sediment, 1.4 * 101
      to 1.1 * 103 ng/g dw in road dust, and 1.8 * 102 and 1.7 * 102 pg/m3 in PM2.5.
      Most of the fractions of anti-DP (fanti) (70%-80%) were consistent among samples.
      The health risk assessment showed that hazard indexes (HIs) of PBDEs or DPs for
      child or adult were all lower than 0.16.

PMID- 29459351
TI  - Hexabromocyclododecane in polystyrene packaging: A downside of recycling?
AB  - While there are no regulatory fire safety obligations for polystyrene (PS) when
      used as packaging material, concerns exist that such packaging material may
      contain the flame retardant hexabromocyclododecane (HBCDD) as a result of
      uncontrolled recycling activities. To evaluate these concerns, we collected 50
      samples of PS packaging materials from the UK and 20 from Ireland. HBCDD was
      detected in 63 (90%) of samples, with concentrations in 4 samples from Ireland
      exceeding the EU's low POP concentration limit (LPCL) of 0.1% above which
      articles may not be recycled. Moreover, 2 further samples contained HBCDD >0.01%.
      While our samples were obtained in the 12 month period prior to the March 2016
      introduction of the EU's 0.01% concentration limit above which articles may not
      be placed on the market, our data suggest that continued monitoring is required
      to assess compliance with this limit value. Ratios of alpha vs. gamma-HBCDD in
      our EPS packaging samples (average = 0.63) exceeded significantly (p = 0.025)
      those in EPS building insulation material samples (average = 0.24) reported
      previously for Ireland. This shift towards alpha-HBCDD in packaging EPS is
      consistent with the additional thermal processing experienced by recycled PS and
      suggests the source of HBCDD in PS packaging is recycled PS insulation foam. This
      is of concern owing to the higher bioavailability and lower metabolic clearance
      of alpha-HBCDD compared to the beta- and gamma-isomers.

PMID- 29459352
TI  - Influence of calcium and phosphate on pH dependency of arsenite and arsenate
      adsorption to goethite.
AB  - In the environment, simultaneous presence of arsenic (As) of different oxidation
      states is common, which hampers our understanding of As behavior. In the current
      study, the pH dependency of arsenite (As(III)) and arsenate (As(V)) adsorption to
      goethite under the influence of calcium (Ca2+) (as a major cation) and phosphate
      (PO43-) (as a major anion) was studied, and the reliability of the CD-MUSIC model
      prediction was tested. The results show that the presence of the major ions led
      in general to a weaker and more complicated pH dependency of As adsorption.
      Calcium promoted As(V) adsorption especially at high pH, which can reverse the
      direction of the pH dependency. The presence of Ca2+ can even decrease As(III)
      adsorption when As(V) and/or PO43- are present. Phosphate competed strongly with
      both As(III) and As(V) in their adsorption, especially at intermediate and low
      pH. In the multi-component system, As(III) adsorbs weaker than As(V) over the
      environmental relevant pH range, therefore it is often the dominant As species in
      solution and soluble As(III) concentration generally decreases with increasing
      pH. In the same pH range, As(V) adsorption shows a complicated pH dependency.
      Soluble As(V) reaches a minimum around pH 6 at high concentration of major
      bivalent cations (e.g. Ca2+), whereas soluble As(V) will decrease with pH at low
      bivalent cation concentrations. The experimental results can be reliably
      predicted and explained with the CD-MUSIC model. The outcome of this study can
      provide understanding needed in the risk assessment and remediation of As
      contaminated soils and water.

PMID- 29459353
TI  - DNA damage in a liver tissue of metal exposed Clethrionomys glareolus.
AB  - It is widely known that some toxic agents may act on DNA strand resulting in its
      damages. One of the possible impairments is formation of abasic sites in DNA. The
      aim of this study was to indicate a presence of these DNA sites in the liver
      tissue of bank voles inhabiting the vicinity of zinc/lead smelters. Samples that
      were used originated from animals collected from unpolluted (Niepolomice,
      Telesnica Oszwarowa, Mikolajki) and polluted (Miasteczko Slaskie, Katowice,
      Olkusz) populations. They significantly differed in terms of tissue lead
      concentrations in the kidney and liver. The means of detected AP sites per 105 bp
      ranged between 3.39 (Telesnica Oszwarowa) to 5.13 (Miasteczko Slaskie).
      Statistical analysis (ANOVA) showed no difference in terms of number of the AP
      sites between single populations. However, t-test showed significant difference
      between the unpolluted and polluted populations. Factorial ANOVA indicated that
      sex is not a factor influencing the number of AP sites. The analyses revealed
      statistically significant relationships between the number of AP sites and Cu
      concentrations in the liver, and also Pb and Cd concentrations in the kidney.

PMID- 29459354
TI  - Mercury and metallothioneins in blood fractions and tissues of captive Morelet's
      crocodiles in Quintana Roo, Mexico.
AB  - Even though studies of heavy metals and their relation with metallothioneins
      (MTs) in reptile tissues have been conducted, research on heavy metals and MTs in
      organs and blood fractions of crocodylians is limited. To date there are no
      studies on the distribution of MTs in organs and their relation with mercury
      (Hg), or the concentration of MTs in plasma and erythrocytes of crocodylians. In
      order to understand the role of MTs in crocodiles, our aim was to assess the
      detoxification mechanisms for exposure to metals in Morelet's crocodile
      (Crocodylus moreletii) by using two biomarkers (Hg and MTs) in blood fractions
      and tissues, and comparing them with concentrations between two populations of
      crocodiles, one previously wild and currently captive (Theme Park) and another
      raised in a Wildlife Management Unit (WMU). The caudal scutes from the Theme Park
      showed higher concentrations of Hg than those from the skin in the WMU samples,
      and significant negative relationships were observed between the total length
      (TL) and Hg in the scutes. The significant negative relationship between Hg and
      hemoglobin (Hb) may be due to disorders in the oxidation process and even
      denature of this protein, while the positive trend observed between MTs and Hb is
      consistent with the detoxifying functions and the protection against oxidative
      damage. This study is the first to report Hg in the erythrocytes of crocodylians
      and the use of MTs for testing the potential of these biomarkers as a tool to
      assess Hg exposure in crocodile's habitats.

PMID- 29459355
TI  - Mobile Phone Ownership Is Not a Serious Barrier to Participation in Studies:
      Descriptive Study.
AB  - BACKGROUND: Rather than providing participants with study-specific data
      collection devices, their personal mobile phones are increasingly being used as a
      means for collecting geolocation and ecological momentary assessment (EMA) data
      in public health research. OBJECTIVE: The purpose of this study was to (1)
      describe the sociodemographic characteristics of respondents to an online survey
      screener assessing eligibility to participate in a mixed methods study collecting
      geolocation and EMA data via the participants' personal mobile phones, and (2)
      examine how eligibility criteria requiring mobile phone ownership and an
      unlimited text messaging plan affected participant inclusion. METHODS: Adult
      (>=18 years) daily smokers were recruited via public advertisements, free weekly
      newspapers, printed flyers, and word of mouth. An online survey screener was used
      as the initial method of determining eligibility for study participation. The
      survey screened for twenty-eight inclusion criteria grouped into three
      categories, which included (1) cell phone use, (2) tobacco use, and (3)
      additional criteria. RESULTS: A total of 1003 individuals completed the online
      screener. Respondents were predominantly African American (605/1003, 60.3%)
      (60.4%), male (514/1003, 51.3%), and had a median age of 35 years (IQR 26-50).
      Nearly 50% (496/1003, 49.5%) were unemployed. Most smoked menthol cigarettes
      (699/1003, 69.7%), and had a median smoking history of 11 years (IQR 5-21). The
      majority owned a mobile phone (739/1003, 73.7%), could install apps (86.8%), used
      their mobile phone daily (89.5%), and had an unlimited text messaging plan
      (871/1003, 86.8%). Of those who completed the online screener, 302 were eligible
      to participate in the study; 163 were eligible after rescreening, and 117 were
      enrolled in the study. Compared to employed individuals, a significantly greater
      proportion of those who were unemployed were ineligible for the study based on
      mobile phone inclusion criteria (P<.001); yet, 46.4% (333/717) of the individuals
      who were unemployed met all mobile phone inclusion criteria. CONCLUSIONS:
      Inclusion criteria requiring participants to use their personal mobile phones for
      data collection was not a major barrier to study participation for most
      respondents who completed the online screener, including those who were
      unemployed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02261363;
      https://clinicaltrials.gov/ct2/show/NCT02261363 (Archived by WebCite at
      http://www.webcitation.org/6wOmDluSt).

PMID- 29459356
TI  - Three-Factor Structure of the eHealth Literacy Scale Among Magnetic Resonance
      Imaging and Computed Tomography Outpatients: A Confirmatory Factor Analysis.
AB  - BACKGROUND: Electronic health (eHealth) literacy is needed to effectively engage
      with Web-based health resources. The 8-item eHealth literacy scale (eHEALS) is a
      commonly used self-report measure of eHealth literacy. Accumulated evidence has
      suggested that the eHEALS is unidimensional. However, a recent study by Sudbury
      Riley and colleagues suggested that a theoretically-informed three-factor model
      fit better than a one-factor model. The 3 factors identified were awareness (2
      items), skills (3 items), and evaluate (3 items). It is important to determine
      whether these findings can be replicated in other populations. OBJECTIVE: The aim
      of this cross-sectional study was to verify the three-factor eHEALS structure
      among magnetic resonance imaging (MRI) and computed tomography (CT) medical
      imaging outpatients. METHODS: MRI and CT outpatients were recruited consecutively
      in the waiting room of one major public hospital. Participants self-completed a
      touchscreen computer survey, assessing their sociodemographic, scan, and internet
      use characteristics. The eHEALS was administered to internet users, and the three
      factor structure was tested using structural equation modeling. RESULTS: Of 405
      invited patients, 87.4% (354/405) were interested in participating in the study,
      and of these, 75.7% (268/354) were eligible. Of the eligible participants, 95.5%
      (256/268) completed all eHEALS items. Factor loadings were 0.80 to 0.94 and
      statistically significant (P<.001). All reliability measures were acceptable
      (indicator reliability: awareness=.71-.89, skills=.78-.80, evaluate=.64-.79;
      composite reliability: awareness=.89, skills=.92, evaluate=.89; variance
      extracted estimates: awareness=.80, skills=.79, evaluate=.72). Two out of three
      goodness-of-fit indices were adequate (standardized root mean square residual
      (SRMR)=.038; comparative fit index (CFI)=.944; root mean square error of
      approximation (RMSEA)=.156). Item 3 was removed because of its significant
      correlation with item 2 (Lagrange multiplier [LM] estimate 104.02; P<.001) and
      high loading on 2 factors (LM estimate 91.11; P<.001). All 3 indices of the
      resulting 7-item model indicated goodness of fit (chi211=11.3; SRMR=.013;
      CFI=.999; RMSEA=.011). CONCLUSIONS: The three-factor eHEALS structure was
      supported in this sample of MRI and CT medical imaging outpatients. Although
      further factorial validation studies are needed, these 3 scale factors may be
      used to identify individuals who could benefit from interventions to improve
      eHealth literacy awareness, skill, and evaluation competencies.

PMID- 29459358
TI  - GP who altered notes of patient who died after DVT was missed is suspended.

PMID- 29459357
TI  - Attitudes Toward e-Mental Health Services in a Community Sample of Adults: Online
      Survey.
AB  - BACKGROUND: Despite evidence that e-mental health services are effective,
      consumer preferences still appear to be in favor of face-to-face services.
      However, the theory of planned behavior (TPB) suggests that cognitive intentions
      are more proximal to behavior and thus may have a more direct influence on
      service use. Investigating individual characteristics that influence both
      preferences and intentions to use e-mental health services is important for
      better understanding factors that might impede or facilitate the use of these
      services. OBJECTIVE: This study explores predictors of preferences and intentions
      to access e-mental health services relative to face-to-face services. Five
      domains were investigated (demographics, technology factors, personality,
      psychopathology, and beliefs), identified from previous studies and informed by
      the Internet interventions model. We expected that more participants would report
      intentions to use e-mental health services relative to reported preferences for
      this type of support and that these 5 domains would be significantly associated
      with both intentions and preferences toward online services. METHODS: A mixed
      sample of 308 community members and university students was recruited through
      social media and the host institution in Australia. Ages ranged between 17 and 68
      years, and 82.5% (254/308) were female. Respondents completed an online survey.
      Chi-square analysis and t tests were used to explore group differences, and
      logistic regression models were employed to explore factors predicting
      preferences and intentions. RESULTS: Most respondents (85.7%, 264/308) preferred
      face-to-face services over e-mental health services. Relative to preferences, a
      larger proportion of respondents (39.6%, 122/308) endorsed intentions to use e
      mental health services if experiencing mental health difficulties in the future.
      In terms of the 5 predictor domains, 95% CIs of odds ratios (OR) derived from
      bootstrapped standard errors suggested that prior experience with online services
      significantly predicted intentions to use self-help (95% CI 2.08-16.24) and
      therapist-assisted (95% CI 1.71-11.90) online services in future. Being older
      predicted increased intentions to use therapist-assisted online services in
      future (95% CI 1.01-1.06), as did more confidence using computers and the
      Internet (95% CI 1.06-2.69). Technology confidence was also found to predict
      greater preference for online services versus face-to-face options (95% CI 1.24
      4.82), whereas higher doctor-related locus of control, or LOC (95% CI 0.76-0.95),
      and extraversion (95% CI 0.88-1.00) were predictive of lower likelihood of
      preferring online services relative to face-to-face services. CONCLUSIONS:
      Despite generally low reported preferences toward e-mental health services,
      intentions to access these services are higher, raising the question of how to
      best encourage translation of intentions into behavior (ie, actual use of
      programs). Strategies designed to ease people into new Internet-based mental
      health programs (to enhance confidence and familiarity) may be important for
      increasing the likelihood that they will return to such programs later.

PMID- 29459360
TI  - Phosphorylation of BACH1 switches its function from transcription factor to
      mitotic chromosome regulator and promotes its interaction with HMMR.
AB  - The transcription repressor BACH1 performs mutually independent dual roles in
      transcription regulation and chromosome alignment during mitosis by supporting
      polar ejection force of mitotic spindle. We now found that the mitotic spindles
      became oblique relative to the adhesion surface following endogenous BACH1
      depletion in HeLa cells. This spindle orientation rearrangement was rescued by re
      expression of BACH1 depending on its interactions with HMMR and CRM1, both of
      which are required for the positioning of mitotic spindle, but independently of
      its DNA-binding activity. A mass spectrometry analysis of BACH1 complexes in
      interphase and M phase revealed that BACH1 lost during mitosis interactions with
      proteins involved in chromatin and gene expression but retained interactions with
      HMMR and its known partners including CHICA. By analyzing BACH1 modification
      using stable isotope labeling with amino acids in cell culture, mitosis-specific
      phosphorylations of BACH1 were observed, and mutations of these residues
      abolished the activity of BACH1 to restore mitotic spindle orientation in
      knockdown cells and to interact with HMMR. Detailed histological analysis of
      Bach1-deficient mice revealed lengthening of the epithelial fold structures of
      the intestine. These observations suggest that BACH1 performs stabilization of
      mitotic spindle orientation together with HMMR and CRM1 in mitosis, and that the
      cell cycle-specific phosphorylation switches the transcriptional and mitotic
      functions of BACH1.

PMID- 29459359
TI  - Impact of dietary patterns and the main food groups on mortality and recurrence
      in cancer survivors: a systematic review of current epidemiological literature.
AB  - OBJECTIVE: To determine whether there is an association between dietary
      patterns/indices and foods from the main food groups (highest vs lowest intakes)
      prior to or after cancer diagnosis and mortality and cancer recurrence in cancer
      survivors. PARTICIPANTS: Survivors of common cancers with a 10-year survival rate
      of >=50%: bladder, bowel, breast, cervical, kidney, laryngeal, prostate,
      testicular, uterine cancer, malignant melanoma and (non-)Hodgkin's lymphoma.
      OUTCOME MEASURES: Mortality (overall, cancer-specific, from other causes) and
      cancer recurrence. INFORMATION SOURCES: PubMed, Embase and the Cochrane Library
      were searched from inception to April 2017. Additional studies were identified by
      searching reference lists. Two authors independently screened titles and
      abstracts, assessed study quality and extracted the data. RESULTS: A total of 38
      studies were included. The risk of bias was rated low for the included randomised
      controlled trials (RCTs) and moderate for the cohort studies. The quality of
      evidence was assessed with the Grading of Recommendations, Assessment,
      Development and Evaluations (GRADE) approach and was rated moderate (RCTs), and
      (very)low (cohort studies). Reducing the amount of fat after diagnosis appears to
      decrease the risk of breast cancer recurrence. Adherence to a high-quality diet
      and prudent diet after diagnosis appears to decrease the risk of death from other
      causes (and overall mortality for high-quality diet) in breast cancer survivors.
      Adherence to a Western diet, before and after diagnosis, appears to increase the
      risk of overall mortality and death from other causes among breast cancer
      survivors. Evidence from studies among other cancer survivors was too limited or
      could not be identified. CONCLUSION: For many cancer survivors, there is little
      evidence to date to indicate that particular dietary behaviours influence
      outcomes with regard to recurrence and mortality. Notwithstanding, limited
      evidence suggests that a low-fat diet, a high-quality diet and a prudent diet are
      beneficial for breast cancer survivors, while a Western diet is detrimental for
      breast cancer survivors.

PMID- 29459362
TI  - Cardiovascular Complications in Pregnancy: It Is Time for Action.

PMID- 29459361
TI  - Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly
      Patients With Acute Coronary Syndromes Undergoing Early Percutaneous
      Revascularization.
AB  - BACKGROUND: Elderly patients are at elevated risk of both ischemic and bleeding
      complications after an acute coronary syndrome and display higher on-clopidogrel
      platelet reactivity compared with younger patients. Prasugrel 5 mg provides more
      predictable platelet inhibition compared with clopidogrel in the elderly,
      suggesting the possibility of reducing ischemic events without increasing
      bleeding. METHODS: In a multicenter, randomized, open-label, blinded end point
      trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the
      standard clopidogrel 75 mg in patients >74 years of age with acute coronary
      syndrome undergoing percutaneous coronary intervention. The primary end point was
      the composite of mortality, myocardial infarction, disabling stroke, and
      rehospitalization for cardiovascular causes or bleeding within 1 year. The study
      was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg.
      RESULTS: Enrollment was interrupted, according to prespecified criteria, after a
      planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had
      been enrolled with a median follow-up of 12 months, because of futility for
      efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and
      121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78
      1.30; P=0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel
      versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13
      1.00; P=0.06). Bleeding Academic Research Consortium types 2 and greater rates
      were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95%
      confidence interval, 0.85-3.16; P=0.18). CONCLUSIONS: The present study in
      elderly patients with acute coronary syndromes showed no difference in the
      primary end point between reduced-dose prasugrel and standard-dose clopidogrel.
      However, the study should be interpreted in light of the premature termination of
      the trial. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov.
      Unique identifier: NCT01777503.

PMID- 29459363
TI  - Heart Failure Stimulates Tumor Growth by Circulating Factors.
AB  - BACKGROUND: Heart failure (HF) survival has improved, and nowadays, many patients
      with HF die of noncardiac causes, including cancer. Our aim was to investigate
      whether a causal relationship exists between HF and the development of cancer.
      METHODS: HF was induced by inflicting large anterior myocardial infarction in
      APCmin mice, which are prone to developing precancerous intestinal tumors, and
      tumor growth was measured. In addition, to rule out hemodynamic impairment, a
      heterotopic heart transplantation model was used in which an infarcted or sham
      operated heart was transplanted into a recipient mouse while the native heart was
      left in situ. After 6 weeks, tumor number, volume, and proliferation were
      quantified. Candidate secreted proteins were selected because they were
      previously associated both with (colon) tumor growth and with myocardial
      production in post-myocardial infarction proteomic studies. Myocardial gene
      expression levels of these selected candidates were analyzed, as well as their
      proliferative effects on HT-29 (colon cancer) cells. We validated these
      candidates by measuring them in plasma of healthy subjects and patients with HF.
      Finally, we associated the relation between cardiac specific and inflammatory
      biomarkers and new-onset cancer in a large, prospective general population
      cohort. RESULTS: The presence of failing hearts, both native and heterotopically
      transplanted, resulted in significantly increased intestinal tumor load of 2.4
      fold in APCmin mice (all P<0.0001). The severity of left ventricular dysfunction
      and fibrotic scar strongly correlated with tumor growth ( P=0.002 and P=0.016,
      respectively). We identified several proteins (including serpinA3 and A1,
      fibronectin, ceruloplasmin, and paraoxonase 1) that were elevated in human
      patients with chronic HF (n=101) compared with healthy subjects (n=180; P<0.001).
      Functionally, serpinA3 resulted in marked proliferation effects in human colon
      cancer (HT-29) cells, associated with Akt-S6 phosphorylation. Finally, elevated
      cardiac and inflammation biomarkers in apparently healthy humans (n=8319) were
      predictive of new-onset cancer (n=1124) independently of risk factors for cancer
      (age, smoking status, and body mass index). CONCLUSIONS: We demonstrate that the
      presence of HF is associated with enhanced tumor growth and that this is
      independent of hemodynamic impairment and could be caused by cardiac excreted
      factors. A diagnosis of HF may therefore be considered a risk factor for incident
      cancer.

PMID- 29459364
TI  - Choosing the optimum strategy for rTMS.

PMID- 29459365
TI  - Making soft intelligence hard: a multi-site qualitative study of challenges
      relating to voice about safety concerns.
AB  - BACKGROUND: Healthcare organisations often fail to harvest and make use of the
      'soft intelligence' about safety and quality concerns held by their own
      personnel. We aimed to examine the role of formal channels in encouraging or
      inhibiting employee voice about concerns. METHODS: Qualitative study involving
      personnel from three academic hospitals in two countries. Interviews were
      conducted with 165 participants from a wide range of occupational and
      professional backgrounds, including senior leaders and those from the sharp end
      of care. Data analysis was based on the constant comparative method. RESULTS:
      Leaders reported that they valued employee voice; they identified formal
      organisational channels as a key route for the expression of concerns by
      employees. Formal channels and processes were designed to ensure fairness,
      account for all available evidence and achieve appropriate resolution. When
      processed through these formal systems, concerns were destined to become
      evidenced, formal and tractable to organisational intervention. But the way these
      systems operated meant that some concerns were never voiced. Participants were
      anxious about having to process their suspicions and concerns into hard
      evidentiary facts, and they feared being drawn into official procedures designed
      to allocate consequence. Anxiety about evidence and process was particularly
      relevant when the intelligence was especially 'soft'-feelings or intuitions that
      were difficult to resolve into a coherent, compelling reconstruction of an
      incident or concern. Efforts to make soft intelligence hard thus risked creating
      'forbidden knowledge': dangerous to know or share. CONCLUSIONS: The legal and
      bureaucratic considerations that govern formal channels for the voicing of
      concerns may, perversely, inhibit staff from speaking up. Leaders responsible for
      quality and safety should consider complementing formal mechanisms with
      alternative, informal opportunities for listening to concerns.

PMID- 29459366
TI  - Engorged medullary vein on CT angiography in patients with dural arteriovenous
      fistula: prevalence, types, and comparison between regional and extensive types.
AB  - BACKGROUND AND PURPOSE: Engorged medullary vein (EMV) in patients with
      intracranial dural arteriovenous fistula (DAVF) suggests venous congestion. The
      aim of this study is to investigate its prevalence, pattern, and correlation with
      clinical findings. MATERIALS AND METHODS: CT angiography (CTA) raw data of DAVF
      were used for multiplanar reconstruction and then analyzed for the presence and
      pattern of EMV, which is defined as a dilated vein in the cerebral white matter.
      Patients with EMV were divided into two groups: regional and extensive. Regional
      type is defined as EMV limited to one cerebral hemisphere or cerebellum without
      evidence of subcortical calcification. Extensive type is defined as EMV
      involvement of more than one cerebral hemisphere or both the cerebrum and
      cerebellum. Descriptive analysis of clinical information, DAVF characteristics,
      and other imaging findings was conducted. Clinical information, including
      demographic data, clinical presentation, and hemorrhage, were correlated with
      both types of EMV. RESULTS: Among 192 eligible patients with DAVF, 71 (37%) had
      EMV. Patients with EMV were older (63 years vs 56 years, P=0.02), with DAVF more
      often at the transverse and sigmoid sinus (P<0.001), and more often presented
      with aggressive symptoms (59% vs 34%, P=0.02) than non-EMV patients, but there
      was no difference in the presentation of hemorrhage (15% vs 16%, P=0.99).
      Patients with regional EMV had a higher proportion of hemorrhage than those with
      the extensive type (24% vs 0%, P=0.006). CONCLUSIONS: EMV in patients with DAVF
      is associated with an aggressive manifestation. Regional type EMV is associated
      with a higher risk of a hemorrhagic presentation.

PMID- 29459367
TI  - Endovascular thrombectomy beyond 12 hours of stroke onset: a stroke network's
      experience of late intervention.
AB  - BACKGROUND: Selected patients with proximal anterior circulation ischemic stroke
      who demonstrate limited infarct and sufficient penumbra may benefit from
      endovascular thrombectomy (EVT) beyond conventional time limits. OBJECTIVE: To
      perform a retrospective review of all cases of EVT performed at our institution
      for proximal anterior circulation acute ischemic stroke with onset >12 hours.
      MATERIALS AND METHODS: Patients were assessed with non-contrast CT brain and
      multiphase CT angiography, with Alberta Stroke Program Early CT Score (ASPECTS)
      and collateral grade informing patient selection. Data, including patient
      demographics, workflow, neuroimaging findings, procedural details, recanalization
      rates, and 90-day functional outcomes, were collected. RESULTS: Of the 542
      consecutive endovascular thrombectomy cases performed during the study period, 25
      (4.6%) were >12 hours from stroke onset. Median age was 69 years (IQR 55-80),
      median National Institute of Health Stroke Scale score on presentation was 14
      (IQR 11-18.5), median ASPECTS was 8 (IQR 8-9), and rate of moderate-good
      collateral status was 96% (n=24). Median time to groin puncture was 14 hours 40
      min (IQR 12 hours 36 min - 16 hours 18 min). Rate of successful recanalization
      (modified Thrombolysis in Cerebral infarction 2b-3) was 88% (n=22). Rate of
      functional independence (90-day modified Rankin Scale score 0-2) was 52% (n=13).
      There were no cases of symptomatic intracranial haemorrhage and 90-day mortality
      rate was 12% (n=3). CONCLUSION: With the use of ASPECTS and collateral grade to
      guide patient selection, good functional outcome with acceptable safety
      parameters may be achieved in patients undergoing EVT beyond 12 hours from stroke
      onset.

PMID- 29459368
TI  - Isolated intraventricular hemorrhage secondary to dural arteriovenous fistula.
AB  - Isolated intraventricular hemorrhage due to dural arteriovenous fistula (dAVF) is
      extremely rare and has been reported only a few times in the literature. The
      pathophysiological cause of isolated intraventricular hemorrhage in these cases
      was hypothetically attributed to retrograde venous flow into subependymal
      vessels, although none of these cases demonstrated radiographic evidence of such
      reflux. We present the first case of a dAVF with radiographic evidence of severe
      cortical venous reflux into the subependymal venous network causing isolated
      intraventricular hemorrhage, thus lending proof for the underlying
      pathophysiology. Furthermore, ours is the first case of dAVF with isolated
      intraventricular hemorrhage that was successfully treated using multimodality
      transvenous and transarterial embolization techniques. In cases of high-grade
      dAVF, multimodality treatment may offer the greatest chance for success, and
      should be strongly considered for management.

PMID- 29459369
TI  - The Nucleus Reuniens Controls Long-Range Hippocampo-Prefrontal Gamma
      Synchronization during Slow Oscillations.
AB  - Gamma oscillations are involved in long-range coupling of distant regions that
      support various cognitive operations. Here we show in adult male rats that
      synchronized bursts of gamma oscillations bind the hippocampus (HPC) and
      prefrontal cortex (mPFC) during slow oscillations and slow-wave sleep, a brain
      state that is central for consolidation of memory traces. These gamma bursts
      entrained the firing of the local HPC and mPFC neuronal populations. Neurons of
      the nucleus reuniens (NR), which is a structural and functional hub between HPC
      and mPFC, demonstrated a specific increase in their firing before gamma burst
      onset, suggesting their involvement in HPC-mPFC binding. Chemical inactivation of
      NR disrupted the temporal pattern of gamma bursts and their synchronization, as
      well as mPFC neuronal firing. We propose that the NR drives long-range hippocampo
      prefrontal coupling via gamma bursts providing temporal windows for information
      exchange between the HPC and mPFC during slow-wave sleep.SIGNIFICANCE STATEMENT
      Long-range coupling between hippocampus (HPC) and prefrontal cortex (mPFC) is
      believed to support numerous cognitive functions, including memory consolidation
      occurring during sleep. Gamma-band synchronization is a fundamental process in
      many neuronal operations and is instrumental in long-range coupling. Recent
      evidence highlights the role of nucleus reuniens (NR) in consolidation; however,
      how it influences hippocampo-prefrontal coupling is unknown. In this study, we
      show that HPC and mPFC are synchronized by gamma bursts during slow oscillations
      in anesthesia and natural sleep. By manipulating and recording the NR-HPC-mPFC
      network, we provide evidence that the NR actively promotes this long-range gamma
      coupling. This coupling provides the hippocampo-prefrontal circuit with a novel
      mechanism to exchange information during slow-wave sleep.

PMID- 29459370
TI  - Visual Working Memory Is Independent of the Cortical Spacing Between Memoranda.
AB  - The sensory recruitment hypothesis states that visual short-term memory is
      maintained in the same visual cortical areas that initially encode a stimulus'
      features. Although it is well established that the distance between features in
      visual cortex determines their visibility, a limitation known as crowding, it is
      unknown whether short-term memory is similarly constrained by the cortical
      spacing of memory items. Here, we investigated whether the cortical spacing
      between sequentially presented memoranda affects the fidelity of memory in humans
      (of both sexes). In a first experiment, we varied cortical spacing by taking
      advantage of the log-scaling of visual cortex with eccentricity, presenting
      memoranda in peripheral vision sequentially along either the radial or tangential
      visual axis with respect to the fovea. In a second experiment, we presented
      memoranda sequentially either within or beyond the critical spacing of visual
      crowding, a distance within which visual features cannot be perceptually
      distinguished due to their nearby cortical representations. In both experiments
      and across multiple measures, we found strong evidence that the ability to
      maintain visual features in memory is unaffected by cortical spacing. These
      results indicate that the neural architecture underpinning working memory has
      properties inconsistent with the known behavior of sensory neurons in visual
      cortex. Instead, the dissociation between perceptual and memory representations
      supports a role of higher cortical areas such as posterior parietal or prefrontal
      regions or may involve an as yet unspecified mechanism in visual cortex in which
      stimulus features are bound to their temporal order.SIGNIFICANCE STATEMENT
      Although much is known about the resolution with which we can remember visual
      objects, the cortical representation of items held in short-term memory remains
      contentious. A popular hypothesis suggests that memory of visual features is
      maintained via the recruitment of the same neural architecture in sensory cortex
      that encodes stimuli. We investigated this claim by manipulating the spacing in
      visual cortex between sequentially presented memoranda such that some items
      shared cortical representations more than others while preventing perceptual
      interference between stimuli. We found clear evidence that short-term memory is
      independent of the intracortical spacing of memoranda, revealing a dissociation
      between perceptual and memory representations. Our data indicate that working
      memory relies on different neural mechanisms from sensory perception.

PMID- 29459372
TI  - Detecting Unattended Stimuli Depends on the Phase of Prestimulus Neural
      Oscillations.
AB  - Neural oscillations appear important for perception and attention processes
      because stimulus detection is dependent upon the phase of 7-11 Hz oscillations
      before stimulus onset. Previous work has examined stimulus detection at attended
      locations, but it is unknown whether unattended locations are also subject to
      phasic modulation by ongoing oscillatory activity, as would be predicted by
      theories proposing a role for neural oscillations in organizing general neural
      processing. Here, we recorded brain activity with EEG while human participants of
      both sexes detected brief visual targets preceded by a spatial cue and determined
      whether performance for cued (attended) and uncued (unattended) targets was
      influenced by oscillatory phase across a range of frequencies. Detection of both
      attended and unattended targets depended upon an ~5 Hz theta rhythm and an ~11-15
      Hz alpha rhythm. Critically, detection of unattended stimuli was more strongly
      modulated by the phase of theta oscillations than was detection of attended
      stimuli, suggesting that attentional allocation involves a disengagement from
      ongoing theta sampling. There was no attention-related difference in the strength
      of alpha phase dependence, consistent with a perceptual rather than attentional
      role of oscillatory phase in this frequency range. These results demonstrate the
      importance of neural oscillations in modulating visual processing at both
      attended and unattended locations and clarify one way in which attention may
      produce its effects: through disengagement from low-frequency sampling at
      attended locations.SIGNIFICANCE STATEMENT Past work on the interaction between
      oscillatory phase and neural processing has shown the involvement of posterior ~7
      11 Hz oscillations in visual processing. Most studies, however, have presented
      stimuli at attended locations, making it difficult to disentangle frequencies
      related to attention from those related to perception. Here, we compared the
      oscillatory frequencies involved in the detection of attended and unattended
      stimuli and found that ~11-15 Hz oscillations were related to perception
      independently of attention, whereas ~5 Hz oscillations were more prominent for
      the detection of unattended stimuli. This work demonstrates the importance of
      neural oscillations for mediating stimulus processing at both attended and
      unattended locations and clarifies the different oscillatory frequencies involved
      in attention and perception.

PMID- 29459371
TI  - Dendritic A-Current in Rhythmically Active PreBotzinger Complex Neurons in
      Organotypic Cultures from Newborn Mice.
AB  - The brainstem preBotzinger complex (preBotC) generates the inspiratory rhythm for
      breathing. The onset of neural activity that precipitates the inspiratory phase
      of the respiratory cycle may depend on the activity of type-1 preBotC neurons,
      which exhibit a transient outward K+ current, IA Inspiratory rhythm generation
      can be studied ex vivo because the preBotC remains rhythmically active in vitro,
      both in acute brainstem slices and organotypic cultures. Advantageous optical
      conditions in organotypic slice cultures from newborn mice of either sex allowed
      us to investigate how IA impacts Ca2+ transients occurring in the dendrites of
      rhythmically active type-1 preBotC neurons. The amplitude of dendritic Ca2+
      transients evoked via voltage increases originating from the soma significantly
      increased after an IA antagonist, 4-aminopyridine (4-AP), was applied to the
      perfusion bath or to local dendritic regions. Similarly, glutamate-evoked
      postsynaptic depolarizations recorded at the soma increased in amplitude when 4
      AP was coapplied with glutamate at distal dendritic locations. We conclude that
      IA is expressed on type-1 preBotC neuron dendrites. We propose that IA filters
      synaptic input, shunting sparse excitation, while enabling temporally summated
      events to pass more readily as a result of IA inactivation. Dendritic IA in
      rhythmically active preBotC neurons could thus ensure that inspiratory motor
      activity does not occur until excitatory synaptic drive is synchronized and well
      coordinated among cellular constituents of the preBotC during inspiratory
      rhythmogenesis. The biophysical properties of dendritic IA might thus promote
      robustness and regularity of breathing rhythms.SIGNIFICANCE STATEMENT Brainstem
      neurons in the preBotC generate the oscillatory activity that underlies
      breathing. PreBotC neurons express voltage-dependent currents that can influence
      inspiratory activity, among which is a transient potassium current (IA)
      previously identified in a rhythmogenic excitatory subset of type-1 preBotC
      neurons. We sought to determine whether IA is expressed in the dendrites of
      preBotC. We found that dendrites of type-1 preBotC neurons indeed express IA,
      which may aid in shunting sparse non-summating synaptic inputs, while enabling
      strong summating excitatory inputs to readily pass and thus influence somatic
      membrane potential trajectory. The subcellular distribution of IA in rhythmically
      active neurons of the preBotC may thus be critical for producing well coordinated
      ensemble activity during inspiratory burst formation.

PMID- 29459373
TI  - Neurobiological Mechanisms of Responding to Injustice.
AB  - People are particularly sensitive to injustice. Accordingly, deeper knowledge
      regarding the processes that underlie the perception of injustice, and the
      subsequent decisions to either punish transgressors or compensate victims, is of
      important social value. By combining a novel decision-making paradigm with
      functional neuroimaging, we identified specific brain networks that are involved
      with both the perception of, and response to, social injustice, with reward
      related regions preferentially involved in punishment compared with compensation.
      Developing a computational model of punishment allowed for disentangling the
      neural mechanisms and psychological motives underlying decisions of whether to
      punish and, subsequently, of how severely to punish. Results show that the neural
      mechanisms underlying punishment differ depending on whether one is directly
      affected by the injustice, or whether one is a third-party observer of a
      violation occurring to another. Specifically, the anterior insula was involved in
      decisions to punish following harm, whereas, in third-party scenarios, we found
      amygdala activity associated with punishment severity. Additionally, we used a
      pharmacological intervention using oxytocin, and found that oxytocin influenced
      participants' fairness expectations, and in particular enhanced the frequency of
      low punishments. Together, these results not only provide more insight into the
      fundamental brain mechanisms underlying punishment and compensation, but also
      illustrate the importance of taking an explorative, multimethod approach when
      unraveling the complex components of everyday decision-making.SIGNIFICANCE
      STATEMENT The perception of injustice is a fundamental precursor to many
      disagreements, from small struggles at the dinner table to wasteful conflict
      between cultures and countries. Despite its clear importance, relatively little
      is known about how the brain processes these violations. Taking an
      interdisciplinary approach, we combine methods from neuroscience, psychology, and
      economics to explore the neurobiological mechanisms involved in both the
      perception of injustice as well as the punishment and compensation decisions that
      follow. Using a novel behavioral paradigm, we identified specific brain networks,
      developed a computational model of punishment, and found that administrating the
      neuropeptide oxytocin increases the administration of low punishments of norm
      violations in particular. Results provide valuable insights into the fundamental
      neurobiological mechanisms underlying social injustice.

PMID- 29459376
TI  - Surgeons urge NHS England to ban minimum waits.

PMID- 29459375
TI  - New Scottish GP contract increases risk for remote and rural communities.

PMID- 29459374
TI  - Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual
      Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein
      Kinase-mTORC1 Translational Pathway.
AB  - A homozygous nonsense mutation in the cereblon (CRBN) gene results in autosomal
      recessive, nonsyndromic intellectual disability that is devoid of other
      phenotypic features, suggesting a critical role of CRBN in mediating learning and
      memory. In this study, we demonstrate that adult male Crbn knock-out (CrbnKO)
      mice exhibit deficits in hippocampal-dependent learning and memory tasks that are
      recapitulated by focal knock-out of Crbn in the adult dorsal hippocampus, with no
      changes in social or repetitive behavior. Cellular studies identify deficits in
      long-term potentiation at Schaffer collateral CA1 synapses. We further show that
      Crbn is robustly expressed in the mouse hippocampus and CrbnKO mice exhibit
      hyperphosphorylated levels of AMPKalpha (Thr172). Examination of processes
      downstream of AMP-activated protein kinase (AMPK) finds that CrbnKO mice have a
      selective impairment in mediators of the mTORC1 translation initiation pathway in
      parallel with lower protein levels of postsynaptic density glutamatergic proteins
      and higher levels of excitatory presynaptic markers in the hippocampus with no
      change in markers of the unfolded protein response or autophagy pathways. Acute
      pharmacological inhibition of AMPK activity in adult CrbnKO mice rescues learning
      and memory deficits and normalizes hippocampal mTORC1 activity and postsynaptic
      glutamatergic proteins without altering excitatory presynaptic markers. Thus,
      this study identifies that loss of Crbn results in learning, memory, and synaptic
      defects as a consequence of exaggerated AMPK activity, inhibition of mTORC1
      signaling, and decreased glutamatergic synaptic proteins. Thus, CrbnKO mice serve
      as an ideal model of intellectual disability to further explore molecular
      mechanisms of learning and memory.SIGNIFICANCE STATEMENT Intellectual disability
      (ID) is one of the most common neurodevelopmental disorders. The cereblon (CRBN)
      gene has been linked to autosomal recessive, nonsyndromic ID, characterized by an
      intelligence quotient between 50 and 70 but devoid of other phenotypic features,
      making cereblon an ideal protein for the study of the fundamental aspects of
      learning and memory. Here, using the cereblon knock-out mouse model, we show that
      cereblon deficiency disrupts learning, memory, and synaptic function via AMP
      activated protein kinase hyperactivity, downregulation of mTORC1, and
      dysregulation of excitatory synapses, with no changes in social or repetitive
      behaviors, consistent with findings in the human population. This establishes the
      cereblon knock-out mouse as a model of pure ID without the confounding behavioral
      phenotypes associated with other current models of ID.

PMID- 29459378
TI  - Role of allostatic load and health behaviours in explaining socioeconomic
      disparities in mortality: a structural equation modelling approach.
AB  - BACKGROUND: The relationship between socioeconomic status and mortality has been
      well established; however, the extent to which biological factors mediate this
      relationship is less clear, and empirical evidence from non-Western settings is
      limited. Allostasis, a cumulative measure of physiological dysregulation, has
      been proposed as the underlying mechanism linking socioeconomic status to adverse
      health outcomes. The current study aimed to ascertain the contribution of
      allostatic load (AL) and health behaviours to socioeconomic inequalities in
      mortality among Korean adults. METHODS: The sample comprised 70 713 middle-aged
      and older-aged adults, aged 40-79 years from the Korean Metabolic Syndrome
      Mortality Study. Using structural equation modelling (SEM), mediation analyses
      were performed to estimate the effects of socioeconomic position (SEP) on
      mortality over the follow-up and the extent to which AL, physical exercise and
      non-smoking status mediate the association between SEP and mortality. RESULTS: A
      total of 5618 deaths (7.9%) occurred during the mean follow-up of 15.2 years (SD
      2.9). SEM confirmed a direct significant effect of SEP on mortality, as well as
      significant indirect paths through AL, physical exercise and non-smoking status.
      CONCLUSIONS: Our findings provide support for the mediating role of AL and health
      behaviours in the link between SEP and mortality. Policies designed to reduce
      social disparities in mortality in the long term should primarily focus on
      reducing stress and promoting healthy lifestyles among the socially disadvantaged
      groups. Future studies should further assess the role of other mediators such as
      psychosocial factors, which may contribute to socioeconomic inequalities in
      mortality.

PMID- 29459377
TI  - Gender differences in the use of anti-infective medications before and after
      widowhood: a register-based study.
AB  - BACKGROUND: Recent findings suggest that bereavement due to spousal loss is
      associated with a decline in general immune functions, and thus to increased
      susceptibility to infections among widowed individuals. The present study aims to
      investigate whether spousal loss weakens immune defences more among men than
      among women using a 5% random sample of the total Danish population, and anti
      infective medication use as a proxy for immune response. METHODS: We followed
      6076 Danish individuals (67% women) aged >=50 from 5 years before and up to 5
      years after widowhood to examine changes in prescriptions of anti-infectives for
      systemic use. RESULTS: Women used more anti-infective drugs both before and after
      spousal loss (women: OR= 1.31; 95% CI 1.21 to 1.42). The age-related changes in
      the use of anti-infective medications in the period before widowhood were similar
      to that in the period after widowhood among both men and women. Also, age-related
      changes in the use of anti-infective medications were similar in both genders.
      CONCLUSIONS: The present study shows that individuals are more likely to use anti
      infective medication after being widowed than before being widowed, but this
      change is likely to be related to increasing age and it is similar in both
      genders.

PMID- 29459379
TI  - OxyContin maker stops marketing opioids, as report details payments to advocacy
      groups.

PMID- 29459380
TI  - Convergent molecular defects underpin diverse neurodegenerative diseases.
AB  - In our ageing population, neurodegenerative disorders carry an enormous personal,
      societal and economic burden. Although neurodegenerative diseases are often
      thought of as clinicopathological entities, increasing evidence suggests a
      considerable overlap in the molecular underpinnings of their pathogenesis. Such
      overlapping biological processes include the handling of misfolded proteins,
      defective organelle trafficking, RNA processing, synaptic health and
      neuroinflammation. Collectively but in different proportions, these biological
      processes in neurons or non-neuronal cells lead to regionally distinct patterns
      of neuronal vulnerability and progression of pathology that could explain the
      disease symptomology. With the advent of patient-derived cellular models and
      novel genetic manipulation tools, we are now able to interrogate this commonality
      despite the cellular complexity of the brain in order to develop novel
      therapeutic strategies to prevent or arrest neurodegeneration. Here, we describe
      broadly these concepts and their relevance across neurodegenerative diseases.

PMID- 29459381
TI  - A Patient with Hemolytic Uremic Syndrome and Kidney Failure.

PMID- 29459382
TI  - GMC chair's reply to Nick Ross's second letter regarding Hadiza Bawa-Garba.

PMID- 29459383
TI  - Abdominal migraine.

PMID- 29459384
TI  - There is an urgent need for evidence-based internationally agreed guidelines for
      the assessment of neonates at risk of developing early-onset sepsis.

PMID- 29459385
TI  - Nurse education needed to address uncertainties of role and contribution in
      stroke rehabilitation units.

PMID- 29459386
TI  - School nurses are able to support adolescents experiencing pain secondary to
      stress and unhealthy lifestyle choices.

PMID- 29459387
TI  - Increased physical activity in older adults is associated with decreased fear of
      falling.

PMID- 29459388
TI  - UK news media representations of smoking, smoking policies and tobacco bans in
      prisons.
AB  - BACKGROUND: Prisoner smoking rates remain high, resulting in secondhand smoke
      exposures for prison staff and non-smoker prisoners. Several jurisdictions have
      introduced prison smoking bans with little evidence of resulting disorder.
      Successful implementation of such bans requires staff support. As news media
      representations of health and other issues shape public views and as prison
      smoking bans are being introduced in the UK, we conducted content analysis of UK
      news media to explore representations of smoking in prisons and smoke-free
      prisons. METHODS: We searched 64 national and local newspapers and 5 broadcast
      media published over 17 months during 2015-2016, and conducted thematic analysis
      of relevant coverage in 106 articles/broadcasts. RESULTS: Coverage was relatively
      infrequent and lacked in-depth engagement with the issues. It tended to reinforce
      a negative view of prisoners, avoid explicit concern for prisoner or prison staff
      health and largely ignore the health gains of smoke-free policies. Most coverage
      failed to discuss appropriate responses or support for cessation in the prison
      context, or factors associated with high prisoner smoking rates. Half the
      articles/broadcasts included coverage suggesting smoke-free prisons might lead to
      unrest or instability. CONCLUSIONS: Negative news media representations of
      prisoners and prison smoking bans may impact key stakeholders' views (eg, prison
      staff, policy-makers) on the introduction of smoke-free prison policies. Policy
      makers' communications when engaging in discussion around smoke-free prison
      policies should draw on the generally smooth transitions to smoke-free prisons to
      date, and on evidence on health benefits of smoke-free environments and smoking
      cessation.

PMID- 29459389
TI  - Tobacco industry misappropriation of American Indian culture and traditional
      tobacco.
AB  - OBJECTIVE: Describe the extent to which tobacco industry marketing tactics
      incorporated American Indian culture and traditional tobacco. METHODS: A keyword
      search of industry documents was conducted using document archives from the Truth
      Tobacco Documents Library. Tobacco industry documents (n=76) were analysed for
      themes. RESULTS: Tobacco industry marketing tactics have incorporated American
      Indian culture and traditional tobacco since at least the 1930s, with these
      tactics prominently highlighted during the 1990s with Natural American Spirit
      cigarettes. Documents revealed the use of American Indian imagery such as
      traditional headdresses and other cultural symbols in product branding and the
      portrayal of harmful stereotypes of Native people in advertising. The historical
      and cultural significance of traditional tobacco was used to validate
      commercially available tobacco. CONCLUSIONS: The tobacco industry has
      misappropriated culture and traditional tobacco by misrepresenting American
      Indian traditions, values and beliefs to market and sell their products for
      profit. Findings underscore the need for ongoing monitoring of tobacco industry
      marketing tactics directed at exploiting Native culture and counter-marketing
      tactics that raise awareness about the distinction between commercial and
      traditional tobacco use. Such efforts should be embedded within a culturally
      sensitive framework to reduce the burden of commercial tobacco use.

PMID- 29459390
TI  - First Pass Effect: A New Measure for Stroke Thrombectomy Devices.
AB  - BACKGROUND AND PURPOSE: In acute ischemic stroke, fast and complete
      recanalization of the occluded vessel is associated with improved outcomes. We
      describe a novel measure for newer generation devices: the first pass effect
      (FPE). FPE is defined as achieving a complete recanalization with a single
      thrombectomy device pass. METHODS: The North American Solitaire Acute Stroke
      Registry database was used to identify a FPE subgroup. Their baseline features
      and clinical outcomes were compared with non-FPE patients. Clinical outcome
      measures included 90-days modified Rankin Scale score, National Institutes of
      Health Stroke Scale score, mortality, and symptomatic intracranial hemorrhage.
      Multivariate analyses were performed to determine whether FPE independently
      resulted in improved outcomes and to identify predictors of FPE. RESULTS: A total
      of 354 acute ischemic stroke patients underwent thrombectomy in the North
      American Solitaire Acute Stroke registry. FPE was achieved in 89 out of 354
      (25.1%). More middle cerebral artery occlusions (64% versus 52.5%) and fewer
      internal carotid artery occlusions (10.1% versus 27.7%) were present in the FPE
      group. Balloon guide catheters were used more frequently with FPE (64.0% versus
      34.7%). Median time to revascularization was significantly faster in the FPE
      group (median 34 versus 60 minutes; P=0.0003). FPE was an independent predictor
      of good clinical outcome (modified Rankin Scale score <=2 was seen in 61.3% in
      FPE versus 35.3% in non-FPE cohort; P=0.013; odds ratio, 1.7; 95% confidence
      interval, 1.1-2.7). The independent predictors of achieving FPE were use of
      balloon guide catheters and non-internal carotid artery terminus occlusion.
      CONCLUSIONS: The achievement of complete revascularization from a single
      Solitaire thrombectomy device pass (FPE) is associated with significantly higher
      rates of good clinical outcome. The FPE is more frequently associated with the
      use of balloon guide catheters and less likely to be achieved with internal
      carotid artery terminus occlusion.

PMID- 29459392
TI  - Charting the Course: Risk Scores for Major Bleeding in Transient Ischemic Attack
      and Ischemic Stroke.

PMID- 29459391
TI  - Los Angeles Motor Scale to Identify Large Vessel Occlusion: Prehospital
      Validation and Comparison With Other Screens.
AB  - BACKGROUND AND PURPOSE: Prehospital scales have been developed to identify
      patients with acute cerebral ischemia (ACI) because of large vessel occlusion
      (LVO) for direct routing to Comprehensive Stroke Centers (CSCs), but few have
      been validated in the prehospital setting, and their impact on routing of
      patients with intracranial hemorrhage has not been delineated. The purpose of
      this study was to validate the Los Angeles Motor Scale (LAMS) for LVO and CSC
      appropriate (LVO ACI and intracranial hemorrhage patients) recognition and
      compare the LAMS to other scales. METHODS: The performance of the LAMS,
      administered prehospital by paramedics to consecutive ambulance trial patients,
      was assessed in identifying (1) LVOs among all patients with ACI and (2) CSC
      appropriate patients among all suspected strokes. Additionally, the LAMS
      administered postarrival was compared concurrently with 6 other scales proposed
      for paramedic use and the full National Institutes of Health Stroke Scale.
      RESULTS: Among 94 patients, age was 70 (+/-13) and 49% female. Final diagnoses
      were ACI in 76% (because of LVO in 48% and non-LVO in 28%), intracranial
      hemorrhage in 19%, and neurovascular mimic in 5%. The LAMS administered by
      paramedics in the field performed moderately well in identifying LVO among
      patients with ACI (C statistic, 0.79; accuracy, 0.72) and CSC-appropriate among
      all suspected stroke transports (C statistic, 0.80; accuracy, 0.72). When
      concurrently performed in the emergency department postarrival, the LAMS showed
      comparable or better accuracy versus the 7 comparator scales, for LVO among ACI
      (accuracies LAMS, 0.70; other scales, 0.62-0.68) and CSC-appropriate (accuracies
      LAMS, 0.73; other scales, 0.56-0.73). CONCLUSIONS: The LAMS performed in the
      field by paramedics identifies LVO and CSC-appropriate patients with good
      accuracy. The LAMS performs comparably or better than more extended prehospital
      scales and the full National Institutes of Health Stroke Scale.

PMID- 29459393
TI  - Rodent Models of Cerebral Microinfarct and Microhemorrhage.

PMID- 29459394
TI  - Hyperintense Vessels, Collateralization, and Functional Outcome in Patients With
      Stroke Receiving Endovascular Treatment.
AB  - BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery hyperintense vessels
      (FHV) are frequently observed on magnetic resonance imaging in acute stroke
      patients with proximal vessel occlusion. Whether FHV can serve as a surrogate for
      the collateral status and predict functional outcome of patients is still a
      matter of debate. METHODS: Acute ischemic stroke patients with M1-middle cerebral
      artery occlusion who received magnetic resonance imaging before endovascular
      treatment in 3 hospitals in Germany between January 2007 and June 2016 were
      eligible. Quantification of FHV was performed using an FHV-Alberta Stroke Program
      Early CT Score (ASPECTS) rating system. Functional outcome was evaluated with the
      modified Rankin Scale 3 months after stroke. Collateral status of patients was
      graded on baseline angiography using the American Society of Interventional and
      Therapeutic Neuroradiology grading system. Odds for good outcome (modified Rankin
      Scale score, 0-2) were determined using logistic regression analyses. RESULTS:
      Overall, 116 patients were analyzed (median age, 74; interquartile range [IQR],
      64-79; median National Institutes of Health Stroke Scale, 14; IQR, 10-19). The
      median FHV-ASPECTS was 2 (IQR, 1-3). Good collateral status (American Society of
      Interventional and Therapeutic Neuroradiology grade 3-4) on angiography was more
      frequently observed in patients with FHV-ASPECTS <=2 (83% versus 57%; P=0.025).
      Patients with an FHV-ASPECTS <=2 had a better functional outcome after 3 months
      (median modified Rankin Scale score, 2; IQR, 0-5), compared with patients with an
      FHV-ASPECTS >2 (median modified Rankin Scale score, 4; IQR, 3-6; P=0.015). In
      multiple regression analyses, FHV-ASPECTS <=2 was independently associated with
      good functional outcome (adjusted odds ratio, 5.3; 95% confidence interval, 1.5
      18.2). CONCLUSIONS: Low FHV-ASPECTS is associated with both better collateral
      status and better 3-month functional outcome in acute stroke patients with M1
      vessel occlusion.

PMID- 29459395
TI  - Effects of Prehospital Thrombolysis in Stroke Patients With Prestroke Dependency.
AB  - BACKGROUND AND PURPOSE: Data on effects of intravenous thrombolysis on outcome of
      patients with ischemic stroke who are dependent on assistance in activities of
      daily living prestroke are scarce. Recent registry based analyses in activities
      of daily -independent patients suggest that earlier start of intravenous
      thrombolysis in the prehospital setting leads to better outcomes when compared
      with the treatment start in hospital. We evaluated whether these observations can
      be corroborated in patients with prestroke dependency. METHODS: This
      observational, retrospective analysis included all patients with acute ischemic
      stroke depending on assistance before stroke who received intravenous
      thrombolysis either on the Stroke Emergency Mobile (STEMO) or through
      conventional in-hospital care (CC) in a tertiary stroke center (Charite, Campus
      Benjamin Franklin, Berlin) during routine care. Prespecified outcomes were
      modified Rankin Scale scores of 0 to 3 and survival at 3 months, as well as
      symptomatic intracranial hemorrhage. Outcomes were adjusted in multivariable
      logistic regression. RESULTS: Between February 2011 and March 2015, 122 of 427
      patients (28%) treated on STEMO and 142 of 505 patients (28%) treated via CC
      needed assistance before stroke. Median onset-to-treatment times were 97
      (interquartile range, 69-159; STEMO) and 135 (interquartile range, 98-184; CC;
      P<0.001) minutes. After 3 months, modified Rankin Scale scores of 0 to 3 was
      observed in 48 STEMO patients (39%) versus 35 CC patients (25%; P=0.01) and 86
      (70%, STEMO) versus 85 (60%, CC) patients were alive (P=0.07). After adjustment,
      STEMO care was favorable with respect to modified Rankin Scale scores of 0 to 3
      (odds ratio, 1.99; 95% confidence interval, 1.02-3.87; P=0.042) with a
      nonsignificant result for survival (odds ratio, 1.73; 95% confidence interval,
      0.95-3.16; P=0.07). Symptomatic intracranial hemorrhage occurred in 5 STEMO
      versus 12 CC patients (4.2% versus 8.5%; P=0.167). CONCLUSIONS: The results of
      this study suggest that earlier, prehospital (as compared with in-hospital) start
      of intravenous thrombolysis in acute ischemic stroke may translate into better
      clinical outcome in patients with prestroke dependency. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02358772.

PMID- 29459396
TI  - Diagnosing Stroke in Acute Dizziness and Vertigo: Pitfalls and Pearls.

PMID- 29459397
TI  - Predictors of Thrombolysis Administration in Mild Stroke: Florida-Puerto Rico
      Collaboration to Reduce Stroke Disparities.
AB  - BACKGROUND AND PURPOSE: Mild stroke is the most common cause for thrombolysis
      exclusion in patients acutely presenting to the hospital. Thrombolysis
      administration in this subgroup is highly variable among different clinicians and
      institutions. We aim to study the predictors of thrombolysis in patients with
      mild ischemic stroke in the FL-PR CReSD registry (Florida-Puerto Rico
      Collaboration to Reduce Stroke Disparities). METHODS: Among 73 712 prospectively
      enrolled patients with a final diagnosis of ischemic stroke or TIA from January
      2010 to April 2015, we identified 7746 cases with persistent neurological
      symptoms and National Institutes of Health Stroke Scale <=5 who arrived within 4
      hours of symptom onset. Multilevel logistic regression analysis with generalized
      estimating equations was used to identify independent predictors of thrombolytic
      administration in the subgroup of patients without contraindications to
      thrombolysis. RESULTS: We included 6826 cases (final diagnosis mild stroke, 74.6%
      and TIA, 25.4%). Median age was 72 (interquartile range, 21); 52.7% men, 70.3%
      white, 12.9% black, 16.8% Hispanic; and median National Institutes of Health
      Stroke Scale, 2 (interquartile range, 3). Patients who received thrombolysis
      (n=1281, 18.7%) were younger (68 versus 72 years), had less vascular risk factors
      (hypertension, diabetes mellitus, and dyslipidemia), had lower risk of prior
      vascular disease (myocardial infarction, peripheral vascular disease, and
      previous stroke), and had a higher presenting median National Institutes of
      Health Stroke Scale (4 versus 2). In the multilevel multivariable model, early
      hospital arrival (arrive by 0-2 hours versus >=3.5 hours; odds ratio [OR], 8.16;
      95% confidence interval [CI], 4.76-13.98), higher National Institutes of Health
      Stroke Scale (OR, 1.87; 95% CI, 1.77-1.98), aphasia at presentation (OR, 1.35;
      95% CI, 1.12-1.62), faster door-to-computed tomography time (OR, 1.81; 95% CI,
      1.53-2.15), and presenting to an academic hospital (OR, 2.02; 95% CI, 1.39-2.95)
      were independent predictors of thrombolysis administration. CONCLUSIONS: Mild
      acutely presenting stroke patients are more likely to receive thrombolysis if
      they are young, white, or Hispanic and arrive early to the hospital with more
      severe neurological presentation. Identification of predictors of thrombolysis is
      important in design of future studies to assess the use of thrombolysis for mild
      stroke.

PMID- 29459398
TI  - Vulnerability to Infarction During Cerebral Ischemia in Migraine Sufferers.
AB  - BACKGROUND AND PURPOSE: Cerebral hyperexcitability in migraine experiencers might
      sensitize brain tissue to ischemia. We investigated whether a personal history of
      migraine is associated with vulnerability to brain ischemia in humans. METHODS:
      Multicenter cohort study of patients with acute ischemic stroke who underwent a
      brain computed tomography perfusion and were scheduled to undergo reperfusion
      therapy. In a case-control design, we compared the proportion of subjects with no
      mismatch, the volume of penumbra salvaged, as well as the final infarct size in a
      group of patients with migraine and a group of patients with no history of
      migraine. RESULTS: We included 61 patients with migraine (34 [55.7%] men; mean
      age, 52.2+/-15.1 years; migraine without aura/migraine with aura, 44/17) and 61
      patients with no history of migraine. The proportion of no-mismatch among
      migraineurs was significantly higher than among nonmigraineurs (17 [27.9%] versus
      7 [11.5%]; P=0.039) and was more prominent among patients with migraine with aura
      (6 [35.3%]; P=0.030) while it was nonsignificantly increased in patients with
      migraine without aura (11 [25.0%]; P=0.114). Migraine, especially migraine with
      aura, was independently associated with a no-mismatch pattern (odds ratio, 2.65;
      95% CI, 0.95-7.41 for migraine; odds ratio, 5.54; 95% CI, 1.28-23.99 for migraine
      with aura), and there was a linear decrease of the proportion of patients with
      migraine with aura with increasing quartiles of mismatch volumes. Patients with
      migraine with aura had also smaller volumes of salvaged penumbra (9.8+/-41.2 mL)
      compared with patients with migraine without aura (36.4+/-54.1 mL) and patients
      with no migraine (45.1+/-55.0 mL; P=0.056). Conversely, there was no difference
      in final infarct size among the 3 migraine subgroups (P=0.312). CONCLUSIONS:
      Migraine is likely to increase individual vulnerability to ischemic stroke during
      the process of acute brain ischemia and might represent, therefore, a potential
      new therapeutic target against occurrence and progression of the ischemic damage.

PMID- 29459400
TI  - Sperm form and function: what do we know about the role of sexual selection?
AB  - Sperm morphological variation has attracted considerable interest and generated a
      wealth of predominantly descriptive studies over the past three centuries. Yet,
      apart from biophysical studies linking sperm morphology to swimming velocity,
      surprisingly little is known about the adaptive significance of sperm form and
      the selective processes underlying its tremendous diversification throughout the
      animal kingdom. Here, we first discuss the challenges of examining sperm
      morphology in an evolutionary context and why our understanding of it is far from
      complete. Then, we review empirical evidence for how sexual selection theory
      applies to the evolution of sperm form and function, including putative secondary
      sexual traits borne by sperm.

PMID- 29459399
TI  - External Validation of Risk Scores for Major Bleeding in a Population-Based
      Cohort of Transient Ischemic Attack and Ischemic Stroke Patients.
AB  - BACKGROUND AND PURPOSE: The S2TOP-BLEED score may help to identify patients at
      high risk of bleeding on antiplatelet drugs after a transient ischemic attack or
      ischemic stroke. The score was derived on trial populations, and its performance
      in a real-world setting is unknown. We aimed to externally validate the S2TOP
      BLEED score for major bleeding in a population-based cohort and to compare its
      performance with other risk scores for bleeding. METHODS: We studied risk of
      bleeding in 2072 patients with a transient ischemic attack or ischemic stroke on
      antiplatelet agents in the population-based OXVASC (Oxford Vascular Study)
      according to 3 scores: S2TOP-BLEED, REACH, and Intracranial-B2LEED3S. Performance
      was assessed with C statistics and calibration plots. RESULTS: During 8302
      patient-years of follow-up, 117 patients had a major bleed. The S2TOP-BLEED score
      showed a C statistic of 0.69 (95% confidence interval [CI], 0.64-0.73) and
      accurate calibration for 3-year risk of major bleeding. The S2TOP-BLEED score was
      much more predictive of fatal bleeding than nonmajor bleeding (C statistics 0.77;
      95% CI, 0.69-0.85 and 0.50; 95% CI, 0.44-0.58). The REACH score had a C statistic
      of 0.63 (95% CI, 0.58-0.69) for major bleeding and the Intracranial-B2LEED3S
      score a C statistic of 0.60 (95% CI, 0.51-0.70) for intracranial bleeding. The
      ratio of ischemic events versus bleeds decreased across risk groups of bleeding
      from 6.6:1 in the low-risk group to 1.8:1 in the high-risk group. CONCLUSIONS:
      The S2TOP-BLEED score shows modest performance in a population-based cohort of
      patients with a transient ischemic attack or ischemic stroke. Although bleeding
      risks were associated with risks of ischemic events, risk stratification may
      still be useful to identify a subgroup of patients at particularly high risk of
      bleeding, in whom preventive measures are indicated.

PMID- 29459401
TI  - Low-dose gonadotropin induction of ovulation in anovulatory women: still needed
      in the age of IVF.
AB  - Low-dose, step-up gonadotropin is the treatment of choice for women with
      polycystic ovary syndrome (PCOS) who have not conceived after anti-oestrogen
      treatment and as an effective alternative to pulsatile GnRH in women with
      hypogonadotropic hypogonadism (HH). There has been, however, no large-scale,
      comparative study between the two groups using low-dose gonadotropins. Here, we
      performed a retrospective, comparative analysis, in a single clinic database, of
      efficacy and safety of induction of ovulation using low-dose gonadotropins in 364
      women with PCOS and 80 women with HH. The rate of ovulation was high in both PCOS
      (83%) and HH (84%) but mono-follicular, ovulatory cycles were more prevalent in
      PCOS than in HH (77% vs 53%, P < 0.0001) and the proportion of cycles that were
      abandoned was higher in HH than in PCOS (25% vs 15%, P < 0.0001). The median
      threshold dose of gonadotropin required to induce ovulation was 75 IU/day in PCOS
      and 113 IU/day in HH (P < 0.001) and the range of doses was greater in HH women.
      Forty-nine percent of women with PCOS and 65% of those with HH conceived (more
      than 90% within 6 cycles of treatment) and had at least one pregnancy. Multiple
      pregnancies (all twins) occurred in only 4% of women with PCOS and 5% of those
      with HH. These findings emphasise the efficacy and safety of low-dose
      gonadotropin treatment for both clomiphene-resistant women with PCOS and those
      with HH. These results highlight the importance of choosing the more
      physiological approach of gonadotropin induction of ovulation in both groups as
      the most appropriate treatment, in preference to IVF.

PMID- 29459402
TI  - Expression and function of Pdcd4 in mouse endometrium during early pregnancy.
AB  - Embryo implantation is a complex process involving synchronised crosstalk between
      a receptive endometrium and functional blastocysts. Apoptosis plays an important
      role in this process as well as in the maintenance of pregnancy. In this study,
      we analysed the expression pattern of programmed cell death 4 (Pdcd4), a gene
      associated with apoptosis in the mouse endometrium, during early pregnancy and
      pseudopregnancy by real-time quantitative polymerase chain reaction, in situ
      hybridisation, Western blotting and immunohistochemistry. The results showed that
      Pdcd4 was increased along with days of pregnancy and significantly reduced at
      implantation sites (IS) from day 5 of pregnancy (D5). The level of Pdcd4 at IS
      was substantially lower than that at interimplantation sites (IIS) on D6 and D7.
      In addition, Pdcd4 expression in the endometrium was reduced in response to
      artificially induced decidualisation in vivo and in vitro Downregulation of Pdcd4
      gene expression in cultured primary stromal cells promoted decidualisation, while
      upregulation inhibited the decidualisation process by increasing apoptosis. These
      results demonstrate that Pdcd4 is involved in stromal cell decidualisation by
      mediating apoptosis and therefore plays a role in embryo implantation in mice.

PMID- 29459403
TI  - The Alternative NF-kappaB Pathway in Regulatory T Cell Homeostasis and
      Suppressive Function.
AB  - CD4+Foxp3+ regulatory T cells (Tregs) are essential regulators of immune
      responses. Perturbation of Treg homeostasis or function can lead to uncontrolled
      inflammation and autoimmunity. Therefore, understanding the molecular mechanisms
      involved in Treg biology remains an active area of investigation. It has been
      shown previously that the NF-kappaB family of transcription factors, in
      particular, the canonical pathway subunits, c-Rel and p65, are crucial for the
      development, maintenance, and function of Tregs. However, the role of the
      alternative NF-kappaB pathway components, p100 and RelB, in Treg biology remains
      unclear. In this article, we show that conditional deletion of the p100 gene,
      nfkb2, in Tregs, resulted in massive inflammation because of impaired suppressive
      function of nfkb2-deficient Tregs. Surprisingly, mice lacking RelB in Tregs did
      not exhibit the same phenotype. Instead, deletion of both relb and nfkb2 rescued
      the inflammatory phenotype, demonstrating an essential role for p100 as an
      inhibitor of RelB in Tregs. Our data therefore illustrate a new role for the
      alternative NF-kappaB signaling pathway in Tregs that has implications for the
      understanding of molecular pathways driving tolerance and immunity.

PMID- 29459404
TI  - Septic Shock Shapes B Cell Response toward an Exhausted-like/Immunoregulatory
      Profile in Patients.
AB  - Septic shock is accompanied by the development of immune dysfunctions whose
      intensity and duration are associated with increased risk of secondary infections
      and mortality. Although B lymphocytes play a pivotal role in the immune response
      to infections, no comprehensive exploration of circulating B cell status has been
      performed during the immunosuppressive phase of septic shock. Thus, our aim was
      to extensively characterize the phenotype and function of B cells in septic
      shock, including IL-10 production. Circulating B lymphocyte phenotype and
      function were evaluated by flow cytometry on fresh whole blood and after ex vivo
      stimulation in adult septic shock patients sampled at day 1, 3, and 6 after the
      onset of shock. The circulating B cell number was reduced in septic shock
      patients, whereas the B cell proportion among total lymphocytes was increased.
      The remaining circulating B lymphocytes presented with decreased MHC class II
      expression and increased CD21low CD95high exhausted-like phenotype but showed no
      change in maturation status. Circulating B cell functions were markedly altered
      after sepsis with reduced ex vivo activation and proliferation capacities.
      Finally, B cell response after septic shock was characterized by a clear
      plasmacytosis and an increased IL-10 production in remaining B cells from
      patients after ex vivo stimulation. During the sepsis-induced immunosuppression
      phase, B cell response is altered and is oriented toward an exhausted
      like/immunoregulatory profile. Further studies are now needed to confirm the
      immunoregulatory properties of B lymphocytes and evaluate their role in sepsis
      induced immunosuppression.

PMID- 29459405
TI  - alphaMbeta2 Is Antiatherogenic in Female but Not Male Mice.
AB  - Atherosclerosis is a complex inflammatory process characterized by monocyte
      recruitment into the arterial wall, their differentiation into macrophages, and
      lipid accumulation. Because integrin alphaMbeta2 (CD11b/CD18) mediates multiple
      diverse functions of leukocytes, we examined its role in atherogenesis. alphaM-/
      /ApoE-/- and ApoE-/- mice were fed a control or high fat diet for 3 or 16 wk to
      induce atherogenesis. Unexpectedly, alphaM deficiency accelerated development of
      atherosclerosis in female but not in male mice. The size of aortic root lesions
      was 3-4.5-fold larger in female alphaM-/-/ApoE-/- than in ApoE-/- mice. Monocyte
      and macrophage content within the lesions was increased 2.5-fold in female alphaM
      /-/ApoE-/- mice due to enhanced proliferation. alphaMbeta2 elimination promoted
      gender-dependent foam cell formation due to enhanced uptake of cholesterol by
      alphaM-/-/ApoE-/- macrophages. This difference was attributed to enhanced
      expression of lipid uptake receptors, CD36 and scavenger receptor A1 (SR-A1), in
      female mice. Macrophages from female alphaM-/-/ApoE-/- mice showed dramatically
      reduced expression of FoxM1 transcription factor and estrogen receptors (ER)
      alpha and beta. As their antagonists inhibited the effect of 17beta-estradiol
      (E2), E2 decreased CD36, SR-A1, and foam cell formation in ApoE-/- macrophages in
      an ERalpha- and ERbeta-dependent manner. However, female alphaM-/-/ApoE-/-
      macrophages failed to respond to E2 and maintained elevated CD36, SR-A1, and
      lipid accumulation. FoxM1 inhibition in ApoE-/- macrophages reduced ERs and
      enhanced CD36 and SR-A1 expression, whereas FoxM1 overexpression in alphaM-/
      /ApoE-/- macrophages reversed their proatherogenic phenotype. We demonstrate a
      new, surprising atheroprotective role of alphaMbeta2 in female ApoE-/- mice.
      alphaMbeta2 maintains ER expression in macrophages and E2-dependent inhibition of
      foam cell formation.

PMID- 29459407
TI  - CrosstalkNet: A Visualization Tool for Differential Co-expression Networks and
      Communities.
AB  - Variations in physiological conditions can rewire molecular interactions between
      biological compartments, which can yield novel insights into gain or loss of
      interactions specific to perturbations of interest. Networks are a promising tool
      to elucidate intercellular interactions, yet exploration of these large-scale
      networks remains a challenge due to their high dimensionality. To retrieve and
      mine interactions, we developed CrosstalkNet, a user friendly, web-based network
      visualization tool that provides a statistical framework to infer condition
      specific interactions coupled with a community detection algorithm for bipartite
      graphs to identify significantly dense subnetworks. As a case study, we used
      CrosstalkNet to mine a set of 54 and 22 gene-expression profiles from breast
      tumor and normal samples, respectively, with epithelial and stromal compartments
      extracted via laser microdissection. We show how CrosstalkNet can be used to
      explore large-scale co-expression networks and to obtain insights into the
      biological processes that govern cross-talk between different tumor
      compartments.Significance: This web application enables researchers to mine
      complex networks and to decipher novel biological processes in tumor epithelial
      stroma cross-talk as well as in other studies of intercompartmental interactions.
      Cancer Res; 78(8); 2140-3. (c)2018 AACR.

PMID- 29459406
TI  - TLR2 Stimulation Strengthens Intrahepatic Myeloid-Derived Cell-Mediated T Cell
      Tolerance through Inducing Kupffer Cell Expansion and IL-10 Production.
AB  - Hepatic APCs play a critical role in promoting immune tolerance in the liver.
      Recently, we have demonstrated that TLR2 stimulation on liver sinusoidal
      endothelial cells reverted their suppressive properties to induce T cell
      immunity. However, there is a paucity of information about how TLR2 stimulation
      modulates the immunological function of other hepatic APCs. In the current study,
      we investigated whether TLR2 stimulation influences the function of intrahepatic
      myeloid-derived cells (iMDCs) and elucidated the mechanisms involved in iMDC
      induced T cell immunity. We could show that iMDCs from C57BL/6 mice can potently
      suppress T cell activation in a cell contact-independent manner. Ag presentation
      by iMDCs leads to naive CD8 T cell tolerance. To our surprise, instead of
      inducing cell functional maturation, TLR2 ligand palmitoyl-3-cysteine-serine
      lysine-4 (P3C) stimulation further strengthens the suppressive and tolerogenic
      properties of iMDCs. After P3C administration, the population of Kupffer cells
      (KCs) of iMDCs dramatically increased. Mechanism analysis shows that KCs are
      essential for the enhanced inhibition of T cell activation by P3C-stimulated
      iMDCs. The iMDC-mediated CD8 T cell inhibition was mediated by soluble mediators,
      one of which was IL-10 secreted by KCs after P3C stimulation. IL-10 blockade
      could partially abolish iMDC-mediated T cell inhibition. Moreover, hepatitis B
      virus particle stimulation on iMDCs could also induce IL-10 production by the
      cells in a TLR2-dependent way. Our results have implications for our
      understanding of liver-specific tolerance and for the development of strategies
      to overcome T cell tolerance in situations such as chronic viral liver
      infections.

PMID- 29459408
TI  - Impact of provision of time in therapeutic range value on anticoagulation
      management in atrial fibrillation patients on warfarin.
AB  - INTRODUCTION: The importance of time in therapeutic range (TTR) in patients
      prescribed warfarin therapy for stroke prevention in atrial fibrillation (AF)
      cannot be overemphasised. AIM: To evaluate the impact of provision of TTR results
      during clinic visits on anticoagulation management. DESIGN: Single-centred,
      randomised controlled study. SETTING: Fifteen arrhythmia clinics in Hong Kong.
      PATIENTS: AF patients prescribed warfarin. INTERVENTIONS: Provision of TTR or no
      provision of TTR. MAIN OUTCOME MEASURES: A documented discussion between doctors
      and patients about switching warfarin to a non-vitamin K oral anticoagulant
      (NOAC). RESULTS: Four hundred and eighty one patients with AF prescribed warfarin
      were randomly assigned to (1) a TTR provision group or (2) control. Their mean
      age was 73.6+/-12.0 years and 60.7% were men. The mean CHA2DS2-VASc score was
      3.2+/-1.6 and the mean HASBLED score was 1.7+/-1.2. The mean TTR was 63.9%+/
      29.9%. At the index clinic visit, 71 of 481 patients (14.8%) had a documented
      discussion about switching warfarin to a NOAC. Patients with provision of TTR
      results were more likely to discuss switching warfarin to a NOAC than controls
      (19.1% vs 10.6%, P=0.03), especially those with a TTR <65% (35.2% vs 10.6%,
      P<0.001). A higher proportion of patients with provision of TTR results switched
      to a NOAC (5.9% vs 4.1%, P=0.49). CONCLUSIONS: The provision of TTR among
      patients on warfarin was associated with a discussion about switching from
      warfarin to a NOAC in those with TTR <65%, but did not result in actual switching
      to a NOAC, suggesting additional barriers.

PMID- 29459409
TI  - Precision measurements on trapped antihydrogen in the ALPHA experiment.
AB  - Both the 1S-2S transition and the ground state hyperfine spectrum have been
      observed in trapped antihydrogen. The former constitutes the first observation of
      resonant interaction of light with an anti-atom, and the latter is the first
      detailed measurement of a spectral feature in antihydrogen. Owing to the narrow
      intrinsic linewidth of the 1S-2S transition and use of two-photon laser
      excitation, the transition energy can be precisely determined in both hydrogen
      and antihydrogen, allowing a direct comparison as a test of fundamental symmetry.
      The result is consistent with CPT invariance at a relative precision of around
      2*10-10 This constitutes the most precise measurement of a property of
      antihydrogen. The hyperfine spectrum of antihydrogen is determined to a relative
      uncertainty of 4*10-4 The excited state and the hyperfine spectroscopy techniques
      currently both show sensitivity at the few 100 kHz level on the absolute scale.
      Here, the most recent work of the ALPHA collaboration on precision spectroscopy
      of antihydrogen is presented together with an outlook on improving the precision
      of measurements involving lasers and microwave radiation. Prospects of measuring
      the Lamb shift and determining the antiproton charge radius in trapped
      antihydrogen in the ALPHA apparatus are presented. Future perspectives of
      precision measurements of trapped antihydrogen in the ALPHA apparatus when the
      ELENA facility becomes available to experiments at CERN are discussed.This
      article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA
      era'.

PMID- 29459410
TI  - Recent progress of laser spectroscopy experiments on antiprotonic helium.
AB  - The Atomic Spectroscopy and Collisions Using Slow Antiprotons (ASACUSA)
      collaboration is currently carrying out laser spectroscopy experiments on
      antiprotonic helium [Formula: see text] atoms at CERN's Antiproton Decelerator
      facility. Two-photon spectroscopic techniques have been employed to reduce the
      Doppler width of the measured [Formula: see text] resonance lines, and determine
      the atomic transition frequencies to a fractional precision of 2.3-5 parts in 109
      More recently, single-photon spectroscopy of buffer-gas cooled [Formula: see
      text] has reached a similar precision. By comparing the results with three-body
      quantum electrodynamics calculations, the antiproton-to-electron mass ratio was
      determined as [Formula: see text], which agrees with the known proton-to-electron
      mass ratio with a precision of 8*10-10 The high-quality antiproton beam provided
      by the future Extra Low Energy Antiproton Ring (ELENA) facility should enable
      further improvements in the experimental precision.This article is part of the
      Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.

PMID- 29459411
TI  - Collisions involving antiprotons and antihydrogen: an overview.
AB  - I give an overview of experimental and theoretical results for antiproton and
      antihydrogen scattering with atoms and molecules (in particular H, He). At low
      energies ([Formula: see text]1 keV) there are practically no experimental data
      available. Instead I compare the results from different theoretical calculations,
      of various degrees of sophistication. At energies up to a few tens of eV, I focus
      on simple approximations that give reasonably accurate results, as these allow
      quick estimates of collision rates without embarking on a research project.This
      article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA
      era'.

PMID- 29459412
TI  - The ASACUSA antihydrogen and hydrogen program: results and prospects.
AB  - The goal of the ASACUSA-CUSP collaboration at the Antiproton Decelerator of CERN
      is to measure the ground-state hyperfine splitting of antihydrogen using an
      atomic spectroscopy beamline. A milestone was achieved in 2012 through the
      detection of 80 antihydrogen atoms 2.7 m away from their production region. This
      was the first observation of 'cold' antihydrogen in a magnetic field free region.
      In parallel to the progress on the antihydrogen production, the spectroscopy
      beamline was tested with a source of hydrogen. This led to a measurement at a
      relative precision of 2.7*10-9 which constitutes the most precise measurement of
      the hydrogen hyperfine splitting in a beam. Further measurements with an upgraded
      hydrogen apparatus are motivated by CPT and Lorentz violation tests in the
      framework of the Standard Model Extension. Unlike for hydrogen, the antihydrogen
      experiment is complicated by the difficulty of synthesizing enough cold antiatoms
      in the ground state. The first antihydrogen quantum states scan at the entrance
      of the spectroscopy apparatus was realized in 2016 and is presented here. The
      prospects for a ppm measurement are also discussed.This article is part of the
      Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.

PMID- 29459414
TI  - Challenging the standard model by high-precision comparisons of the fundamental
      properties of protons and antiprotons.
AB  - The BASE collaboration investigates the fundamental properties of protons and
      antiprotons, such as charge-to-mass ratios and magnetic moments, using advanced
      cryogenic Penning trap systems. In recent years, we performed the most precise
      measurement of the magnetic moments of both the proton and the antiproton, and
      conducted the most precise comparison of the proton-to-antiproton charge-to-mass
      ratio. In addition, we have set the most stringent constraint on directly
      measured antiproton lifetime, based on a unique reservoir trap technique. Our
      matter/antimatter comparison experiments provide stringent tests of the
      fundamental charge-parity-time invariance, which is one of the fundamental
      symmetries of the standard model of particle physics. This article reviews the
      recent achievements of BASE and gives an outlook to our physics programme in the
      ELENA era.This article is part of the Theo Murphy meeting issue 'Antiproton
      physics in the ELENA era'.

PMID- 29459415
TI  - Prospects for comparison of matter and antimatter gravitation with ALPHA-g.
AB  - The ALPHA experiment has recently entered an expansion phase of its experimental
      programme, driven in part by the expected benefits of conducting experiments in
      the framework of the new AD + ELENA antiproton facility at CERN. With
      antihydrogen trapping now a routine operation in the ALPHA experiment, the
      collaboration is leading progress towards precision atomic measurements on
      trapped antihydrogen atoms, with the first excitation of the 1S-2S transition and
      the first measurement of the antihydrogen hyperfine spectrum (Ahmadi et al. 2017
      Nature541, 506-510 (doi:10.1038/nature21040); Nature548, 66-69
      (doi:10.1038/nature23446)). We are building on these successes to extend our
      physics programme to include a measurement of antimatter gravitation. We plan to
      expand a proof-of-principle method (Amole et al. 2013 Nat. Commun.4, 1785
      (doi:10.1038/ncomms2787)), first demonstrated in the original ALPHA apparatus,
      and perform a precise measurement of antimatter gravitational acceleration with
      the aim of achieving a test of the weak equivalence principle at the 1% level.
      The design of this apparatus has drawn from a growing body of experience on the
      simulation and verification of antihydrogen orbits confined within magnetic
      minimum atom traps. The new experiment, ALPHA-g, will be an additional atom
      trapping apparatus located at the ALPHA experiment with the intention of
      measuring antihydrogen gravitation.This article is part of the Theo Murphy
      meeting issue 'Antiproton physics in the ELENA era'.

PMID- 29459416
TI  - The ELENA facility.
AB  - The CERN Antiproton Decelerator (AD) provides antiproton beams with a kinetic
      energy of 5.3 MeV to an active user community. The experiments would profit from
      a lower beam energy, but this extraction energy is the lowest one possible under
      good conditions with the given circumference of the AD. The Extra Low Energy
      Antiproton ring (ELENA) is a small synchrotron with a circumference a factor of 6
      smaller than the AD to further decelerate antiprotons from the AD from 5.3 MeV to
      100 keV. Controlled deceleration in a synchrotron equipped with an electron
      cooler to reduce emittances in all three planes will allow the existing AD
      experiments to increase substantially their antiproton capture efficiencies and
      render new experiments possible. ELENA ring commissioning is taking place at
      present and first beams to a new experiment installed in a new experimental area
      are foreseen in 2017. The transfer lines from ELENA to existing experiments in
      the old experimental area will be installed during CERN Long Shutdown 2 (LS2) in
      2019 and 2020. The status of the project and ring commissioning will be
      reported.This article is part of the Theo Murphy meeting issue 'Antiproton
      physics in the ELENA era'.

PMID- 29459413
TI  - AEgIS at ELENA: outlook for physics with a pulsed cold antihydrogen beam.
AB  - The efficient production of cold antihydrogen atoms in particle traps at CERN's
      Antiproton Decelerator has opened up the possibility of performing direct
      measurements of the Earth's gravitational acceleration on purely antimatter
      bodies. The goal of the AEgIS collaboration is to measure the value of g for
      antimatter using a pulsed source of cold antihydrogen and a Moire
      deflectometer/Talbot-Lau interferometer. The same antihydrogen beam is also very
      well suited to measuring precisely the ground-state hyperfine splitting of the
      anti-atom. The antihydrogen formation mechanism chosen by AEgIS is resonant
      charge exchange between cold antiprotons and Rydberg positronium. A series of
      technical developments regarding positrons and positronium (Ps formation in a
      dedicated room-temperature target, spectroscopy of the n=1-3 and n=3-15
      transitions in Ps, Ps formation in a target at 10 K inside the 1 T magnetic field
      of the experiment) as well as antiprotons (high-efficiency trapping of [Formula:
      see text], radial compression to sub-millimetre radii of mixed [Formula: see
      text] plasmas in 1 T field, high-efficiency transfer of [Formula: see text] to
      the antihydrogen production trap using an in-flight launch and recapture
      procedure) were successfully implemented. Two further critical steps that are
      germane mainly to charge exchange formation of antihydrogen-cooling of
      antiprotons and formation of a beam of antihydrogen-are being addressed in
      parallel. The coming of ELENA will allow, in the very near future, the number of
      trappable antiprotons to be increased by more than a factor of 50. For the
      antihydrogen production scheme chosen by AEgIS, this will be reflected in a
      corresponding increase of produced antihydrogen atoms, leading to a significant
      reduction of measurement times and providing a path towards high-precision
      measurements.This article is part of the Theo Murphy meeting issue 'Antiproton
      physics in the ELENA era'.

PMID- 29459417
TI  - Prospects for testing Lorentz and CPT symmetry with antiprotons.
AB  - A brief overview of the prospects of testing Lorentz and CPT symmetry with
      antimatter experiments is presented. The models discussed are applicable to
      atomic spectroscopy experiments, Penning-trap experiments and gravitational
      tests. Comments about the sensitivity of the most recent antimatter experiments
      to the models reviewed here are included.This article is part of the Theo Murphy
      meeting issue 'Antiproton physics in the ELENA era'.

PMID- 29459418
TI  - Theoretical aspects of antimatter and gravity.
AB  - In this short contribution, I review the physical case of studying the
      gravitational properties of antimatter from a theoretical perspective. I first
      discuss which elements are desirable for any theory where the long-range
      interactions between matter and antimatter differ from those of matter with
      itself. Afterwards I describe the standard way to hide the effects of new forces
      in matter-matter interactions which still allows one to generate ponderable
      matter-antimatter interactions. Finally, I comment on some recent ideas and
      propose some possible future directions.This article is part of the Theo Murphy
      meeting issue 'Antiproton physics in the ELENA era'.

PMID- 29459419
TI  - Antiproton physics in the ELENA era.

PMID- 29459420
TI  - February 19th Question.

PMID- 29459421
TI  - IGF-1 protects SH-SY5Y cells against MPP+-induced apoptosis via PI3K/PDK-1/Akt
      pathway.
AB  - Insulin-like growth factor (IGF)-1 is a well-known anti-apoptotic pro-survival
      factor and phosphatidylinositol-3-kinase (PI3K)/Akt pathway is linked to cell
      survival induced by IGF-1. It is also reported that Akt signaling is modulated by
      3-phosphoinositide-dependent kinase-1 (PDK1). In the current study, we
      investigated whether the anti-apoptotic effect of IGF-1 in SH-SY5Y cells exposed
      to 1-methyl-4-phenylpyridinium (MPP+) is associated with the activity of
      PI3K/PDK1/Akt pathway. Treatment of cells with IGF-1 inhibited MPP+-induced
      apoptotic cell death. IGF-1-induced activation of Akt and the protective effect
      of IGF-1 on MPP+-induced apoptosis were abolished by chemical inhibition of PDK1
      (GSK2334470) or PI3K (LY294002). The phosphorylated levels of Akt and PDK1 were
      significantly suppressed after MPP+ exposure, while IGF-1 treatment completely
      restored MPP+-induced reductions in phosphorylation. IGF-1 protected cells from
      MPP+ insult by suppressing intracellular reactive oxygen species (ROS) production
      and malondialdehyde levels and increasing superoxide dismutase activity.
      Mitochondrial ROS levels were also increased during MPP+ exposure, which were
      attenuated by IGF-1 treatment. In addition, IGF-1-treated cells showed increased
      activities of succinate dehydrogenase and citrate synthase, stabilization of
      mitochondrial transmembrane potential, increased ratio of Bcl-2 to Bax,
      prevention of cytochrome c release and inhibition of caspase-3 activation with
      PARP cleavage. Furthermore, the protective effects of IGF-1 on oxidative stress
      and mitochondrial dysfunction were attenuated when cells were preincubated with
      GSK2334470 or LY294002. Our data suggest that IGF-1 protects SH-SY5Y cells
      against MPP+-associated oxidative stress by preserving mitochondrial integrity
      and inhibiting mitochondrial apoptotic cascades via the activation of
      PI3K/PDK1/Akt pathway.

PMID- 29459422
TI  - Evaluation of near final height in boys with constitutional delay in growth and
      puberty.
AB  - BACKGROUND: This study was conducted to find out whether boys with constitutional
      delay in growth and puberty (CDGP) could attain their target height and predicted
      adult height (PAH) in adulthood or not. METHODS: After measuring the height,
      weight, pubertal stage, parental height and bone age data of the patients at
      their first presentation were extracted from the files and their height and
      weight were measured at the end of the study, wrist X-Ray was performed in order
      to determine the bone age. PAH was calculated using Bayley-Pinneau method and
      target height was estimated by mid parental height. Final or near final heights
      of the patients were measured and compared with the target height and PAH.
      RESULTS: The mean age at presentation and the end of study was 15.2 +/- 0.95, 20
      +/- 0.75 years respectively. Mean of bone age at the beginning of study was 12.97
      +/- 1 years and at the end of study were 17.6 +/- 0.58 years. Mean of delayed
      bone age was 2.2 +/- 0.82 years. Mean of the primary measured heights was 150.16
      +/- 7 cm (138-160 cm). Mean of final or near final heights was 165.7 +/- 2.89 cm
      (161-170.5 cm). Final or near final heights in our subjects were smaller than
      either their PAH (165.7 +/- 2.89 vs 170.7 +/- 5.17) (P value <0.005) or target
      height (165.7 +/- 2.89 vs 171.8 +/- 4.65) (P value <0.0001). CONCLUSION: Most
      patients with CDGP do not reach their target height or predicted adult height;
      they are usually shorter than their parents and general population. Such patients
      need to be followed up until they reach their final height and, in some cases,
      adjunctive medical treatment might be indicated.

PMID- 29459423
TI  - Associations between LPL gene polymorphisms and coronary artery disease: evidence
      based on an updated and cumulative meta-analysis.
AB  - Lipoprotein lipase (LPL) is widely linked to lipid and lipoprotein metabolism,
      but its effects on coronary artery disease (CAD) are not clearly elucidated. The
      aim of this study was to clarify the association between LPL gene polymorphisms
      and CAD susceptibility. The pooled odds ratio (OR) and 95% confidence interval
      (CI) were calculated to estimate the strength of the relationship between LPL
      gene polymorphisms and CAD risk. Comprehensive electronic databases, including
      PubMed, EMBASE, Web of Science, and the Cochrane Library, were systematically
      searched. A total of 45 records containing 80 eligible studies were analyzed. The
      results indicated an increased risk between the LPL D9N polymorphism and
      susceptibility to CAD in the dominant genetic model (AA + GA vs. GG: OR = 1.46,
      95% CI = 1.14-1.87), whereas the LPL HindIII polymorphism showed a protective
      effect against CAD under all tested models (GG+GT vs. TT: OR = 0.85, 95% CI =
      0.75-0.97; GG vs. TT + TG: OR = 0.62, 95% CI = 0.47-0.83; G vs. T: OR = 0.81, 95%
      CI = 0.71-0.92). No significant association was identified for the LPL N291S and
      PvuII polymorphisms. Stratification analysis by ethnicity suggested a significant
      correlation between the LPL S447X polymorphism and CAD susceptibility in
      Caucasians under the dominant and allele genetic models. In summary, our meta
      analysis indicated that the LPL D9N polymorphism was associated with an increased
      risk of CAD, whereas the S447X and HindIII polymorphisms showed protective
      effects. There was no association observed between the N291S and PvuII
      polymorphisms and CAD risk.

PMID- 29459424
TI  - The role of adherens junction proteins in the regulation of insulin secretion.
AB  - In healthy individuals, any rise in blood glucose levels is rapidly countered by
      the release of insulin from the beta-cells of the pancreas which in turn promotes
      the uptake and storage of the glucose in peripheral tissues. The beta-cells
      possess exquisite mechanisms regulating the secretion of insulin to ensure that
      the correct amount of insulin is released. These mechanisms involve tight control
      of the movement of insulin containing secretory vesicles within the beta-cells,
      initially preventing most vesicles being able to move to the plasma membrane.
      Elevated glucose levels trigger an influx of Ca2+ that allows fusion of the small
      number of insulin containing vesicles that are pre-docked at the plasma membrane
      but glucose also stimulates processes that allow other insulin containing
      vesicles located further in the cell to move to and fuse with the plasma
      membrane. The mechanisms controlling these processes are complex and not fully
      understood but it is clear that the interaction of the beta-cells with other beta
      cells in the islets is very important for their ability to develop the
      appropriate machinery for proper regulation of insulin secretion. Emerging
      evidence indicates one factor that is key for this is the formation of homotypic
      cadherin mediated adherens junctions between beta-cells. Here, we review the
      evidence for this and discuss the mechanisms by which these adherens junctions
      might regulate insulin vesicle trafficking as well as the implications this has
      for understanding the dysregulation of insulin secretion seen in pathogenic
      states.

PMID- 29459425
TI  - Inositol Pyrophosphate Synthesis by Diphosphoinositol Pentakisphosphate Kinase-1
      is Regulated by Phosphatidylinositol(4,5)bisphosphate.
AB  - 5-diphosphoinositol tetrakisphosphate (5-InsP7) and bisdiphosphoinositol
      tetrakisphosphate (InsP8) are 'energetic' inositol pyrophosphate signaling
      molecules that regulate bioenergetic homeostasis. Inositol pyrophosphate levels
      are regulated by diphosphoinositol pentakisphosphate kinases (PPIP5Ks); these are
      large modular proteins that host a kinase domain (which phosphorylates 5-InsP7 to
      InsP8), a phosphatase domain that catalyzes the reverse reaction, and a
      polyphosphoinositide-binding domain (PBD). Here, we describe new interactions
      between these three domains in the context of full-length human PPIP5K1. We
      determine that InsP7 kinase activity is dominant when PPIP5K1 is expressed in
      intact cells; in contrast, we found that InsP8 phosphatase activity prevails when
      the enzyme is isolated from its cellular environment. We approach a
      reconciliation of this disparity by showing that cellular InsP8 phosphatase
      activity is inhibited by C8-PtdIns(4,5)P2 (IC50 approx. 40 iM). We recapitulate
      this phosphatase inhibition with natural PtdIns(4,5)P2 that was incorporated into
      large unilamellar vesicles. Additionally, PtdIns(4,5)P2 increases net InsP7
      kinase activity 5-fold. We oftlinedemonstrate that PtdIns(4,5)P2 is not itself a
      phosphatase substrate; its inhibition of InsP8 phosphatase activity results from
      an unusual, functional overlap between the phosphatase domain and the PBD.
      Finally, we discuss the significance of PtdIns(4,5)P2 as a novel regulator of
      PPIP5K1, in relation to compartmentalization of InsP7/InsP8 signaling in vivo.

PMID- 29459427
TI  - Pneumocystis and glucocorticoid use: to prophylax or not to prophylax (and
      when?); that is the question.

PMID- 29459426
TI  - Inhibition of miR-155 attenuates abdominal aortic aneurysm in mice by regulating
      macrophage-mediated inflammation.
AB  - The aim of the present study was to identify abdominal aortic aneurysms (AAA)
      associated miR-155 contributing to AAA pathology by regulating macrophage
      mediated inflammation. Angiotensin II (AngII)-infused apolipoprotein E-deficient
      (ApoE-/-) mice and THP-1 cells model of miR-155 overexpression and deficiency
      were used in the experiments. The expression of miR-155 was detected by
      quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cytokines
      were evaluated using enzyme-linked immunoabsorbent assay (ELISA). Western
      blotting was used to measure the levels of MMP-2, MMP-9, iNOS, and monocyte
      chemoattractant protein (MCP)-1 proteins. Immunostaining and transwell were used
      to determine CD68, elastic collagen, proliferation, and migration of vascular
      smooth muscle cells (VSMCs). The results showed that miR-155 and cytokines were
      up-regulated in AAA patients or ApoE-/- mice. Overexpression of miR-155 enhanced
      MMP-2, MMP-9, iNOS, and MCP-1 levels, and stimulated the proliferation and
      migration of VSMCs. Meanwhile, inhibition of miR-155 had the opposite effect. In
      addition, histology demonstrated accumulation of CD68 and elastic collagen
      positive areas significantly decreased in miR-155 antagomir injection group. In
      conclusion, the results of the present study suggest that inhibiting miR-155 is
      crucial to prevent the development of AAA by regulating macrophage inflammation.

PMID- 29459428
TI  - Attenuation of NK cells facilitates mammary tumor growth in streptozotocin
      induced diabetes in mice.
AB  - Diabetic patients have higher incidence and mortality of cancer. Recent study
      revealed that hyperglycemia-induced oxidative stress is involved in the
      acceleration of tumor metastasis. We used model of high-dose streptozotocin
      induced diabetes to investigate its effect on tumor growth and modulation of
      antitumor immune response of 4T1 murine breast cancer in BALB/c mice. Diabetes
      accelerated tumor appearance, growth and weight, which was associated with
      decreased NK cells cytotoxicity against 4T1 tumor cells in vitro Diabetes reduced
      frequencies of systemic NKG2D+, perforin+, granzyme+, IFN-gamma+ and IL-17+ NK
      cells, while increased level of PD-1 expression and production of IL-10 in NK
      cells. Diabetes decreased percentage of NKG2D+NK cells and increased percentage
      of PD-1+ NK cells also in primary tumor. Diabetes increased accumulation of IL
      10+ Tregs and TGF-beta+ myeloid-derived suppressor cells (MDSCs) in spleen and
      tumor. Diabetic sera in vitro significantly increased the percentage of KLRG-1+
      and PD-1+ NK cells, decreased the percentage of IFN-gamma+NK cells, expression of
      NKp46 and production of perforin, granzyme, CD107a and IL-17 per NK cell in
      comparison to glucose-added mouse sera and control sera. Significantly increased
      percentages of inducible nitric oxide synthase (iNOS) and indoleamine 2,3
      dioxygenase (IDO) producing MDSCs and dendritic cells (DC) were found in the
      spleens of diabetic mice prior to tumor induction. 1-methyl-DL-tryptophan,
      specific IDO inhibitor, almost completely restored phenotype of NK cells
      cultivated in diabetic sera. These findings indicate that diabetes promotes
      breast cancer growth at least in part through increased accumulation of
      immunosuppressive cells and IDO-mediated attenuation of NK cells.

PMID- 29459429
TI  - 14-year case series of eyelid sebaceous gland carcinoma in Chinese patients and
      review of management.
AB  - AIMS: Sebaceous gland carcinoma (SGC) of the eyelid is a rare but potentially
      deadly cancer. The purpose of this study was to determine whether the American
      Joint Committee on Cancer (AJCC) 7th Edition T category for SGC correlated with
      metastasis and survival in the Chinese population. METHODS: This was a
      retrospective, single-centre cohort study. Patients with surgically resected
      eyelid SGC between January 2001 and May 2015 at the Hong Kong Eye Hospital were
      reviewed. Tumours were staged using the AJCC criteria. The main outcome measures
      included local recurrence, metastasis and death. Disease-free survival (DFS) was
      measured from the completion of treatment; overall survival was measured from the
      date of initial diagnosis. RESULTS: The study included 22 Chinese patients with a
      mean age of 65.4 years. The majority presented as a nodular lesion (91%) with 12
      eyes (54.5%) initially misdiagnosed and a mean presentation time of 1 year. It
      was found that those with AJCC stage T2b or higher were significantly associated
      with lymph node metastasis (P=0.002) when compared with those with stage T2a.
      Older age at diagnosis (P=0.035) and no misdiagnosis (P=0.025) were associated
      with shorter DFS. Those with stage 3a or higher were associated with shorter DFS
      (P=0.007) and overall survival (P=0.024). CONCLUSION: Similar to previous
      reports, in this Chinese cohort, AJCC staging for SGC correlated with lymph node
      metastasis, DFS and overall survival. Those with stage 2b or higher on
      presentation will need closer surveillance for lymph node metastasis and may
      benefit from sentinel lymph node biopsy.

PMID- 29459430
TI  - Adalimumab for the treatment of refractory active and inactive non-infectious
      uveitis.
AB  - BACKGROUND/AIMS: To compare the efficacy of adalimumab in eyes with active and
      inactive non-infectious uveitis in the real-world setting. METHODS: Multicentre,
      retrospective, chart review of patients with refractory non-infectious uveitis
      treated with adalimumab. Main outcome measures included reduction of prednisolone
      dose, ability to taper immunosuppressives and a composite endpoint of treatment
      failure encompassing active inflammatory chorioretinal or retinal vascular
      lesions, intraocular inflammation grade and visual acuity. RESULTS: Thirty-seven
      eyes of 22 patients were studied. Mean follow-up was 20.1 months (median: 13).
      Most had either posterior or panuveitis (n=12, 55%). Mean duration of uveitis at
      baseline was 83.2 months (median: 61), where the majority (n=15, 68%) had already
      been treated with two or more conventional immunosuppressive agents in addition
      to prednisolone. Oral prednisolone was reduced to <=10 mg/day in 9 of 12 patients
      (75%) by 6 weeks. At 6 months of therapy, nine (90%) of the active eyes achieved
      a 2-step improvement in anterior chamber inflammation, with six (60%)
      demonstrating a similar improvement in vitreous haze grade. Almost all (n=17,
      94%) of the initially inactive eyes maintained clinical quiescence at this time
      point. The incidence rate of treatment failure during follow-up was 88 per 100
      eye-years for the active eyes and 24 per 100 eye-years for the initially inactive
      eyes. There were no serious adverse effects. CONCLUSION: Adalimumab appears to
      reduce the corticosteroid burden in active and inactive non-infectious uveitis in
      the real-world setting. Inflammatory activity at the time of adalimumab
      commencement may determine long-term treatment success.

PMID- 29459431
TI  - Comparative activity of antimicrobials against Pseudomonas aeruginosa,
      Achromobacter xylosoxidans and Stenotrophomonas maltophilia keratitis isolates.
AB  - BACKGROUND/AIMS: Achromobacter xylosoxidans and Stenotrophomonas maltophilia are
      emerging corneal pathogens, which are closely related to Pseudomonas aeruginosa,
      and have intrinsic resistance to many commonly available antimicrobials. The
      purpose of this study is to compare the in vitro efficacy of 12 antimicrobial
      agents against A. xylosoxidans, S. maltophilia and P. aeruginosa isolates
      recovered from clinical cases of keratitis. METHODS: Recovered corneal isolates
      (n=58) were identified and extracted from the Microbiology Data Bank of the
      Bascom Palmer Eye Institute. Comparative in vitro minimum inhibitory
      concentration (MIC) susceptibility profiles for fluoroquinolones,
      aminoglycosides, beta-lactams and miscellaneous antibiotics were recorded using
      the E-test methodology. Pharmacodynamic indices (Cmax/MIC) were calculated.
      RESULTS: A. xylosoxidans and S. maltophilia isolates were resistant to
      fluoroquinolones, aminoglycosides and ceftazidime (susceptibility rate ranging
      from 0% to 30%) while P. aeruginosa isolates showed a susceptibility rate of 95%
      100% to these antimicrobials (P<0.00001 for the various antimicrobials).
      Exception was moxifloxacin with 80% of susceptibility rate to S. maltophilia
      isolates and Cmax/MIC=10.19. Ninety to 100% susceptibility rates were found for
      minocycline and trimethoprim/sulfamethoxazole for both A. xylosoxidans and S.
      maltophilia. One hundred per cent of the A. xylosoxidans isolates were
      susceptible to piperacillin/tazobactam and ticarcillin/clavulanic acid.
      CONCLUSIONS: There is a significant difference in susceptibility patterns between
      A. xylosoxidans, S. maltophilia and P. aeruginosa. Fluoroquinolones and
      aminoglycosides may not be effective against A. xylosoxidans and S. maltophilia.
      Antibiotics that are not commercially available as eye drops, such as beta
      lactams for A. xylosoxidans, and trimethoprim/sulfamethoxazole and minocycline
      for both A. xylosoxidans and S. maltophilia should be considered.

PMID- 29459433
TI  - Glaucoma awareness Indian military personnel: a tri-service study.
AB  - INTRODUCTION: In India, glaucoma is the third most common cause of blindness,
      reflecting both its asymptomatic presentation and a lack of knowledge in the
      general population. No previous published data of glaucoma awareness among the
      Indian Armed forces personnel exists, who constitute a unique group consisting of
      people drawn from all parts of the country and society. METHODS: Bilingual
      questionnaires were distributed to 496 serving Army, Navy and Air Force personnel
      serving in units local to the Zonal military hospital in North India. Having
      heard of the term glaucoma resulted in the subject being 'glaucoma aware', while
      'knowledge of glaucoma' required at least three out of six questions to be
      answered correctly. RESULTS: 110/496 (22%) participants were found to be glaucoma
      aware, while knowledge of glaucoma was found in 60/496 (12%) participants.
      CONCLUSIONS: This study demonstrates that glaucoma awareness and knowledge is
      high compared with rural or urban Indian populations. This is likely reflects the
      frequent health camps conducted by the armed forces and periodic medical
      examinations. However, these figures are still low compared with developed
      countries and likely reflects differences in education standards, socioeconomic
      status and differing influences of the media.

PMID- 29459434
TI  - 'Inconguous'.

PMID- 29459435
TI  - Membrane cholesterol depletion as a trigger of Nav1.9 channel-mediated
      inflammatory pain.
AB  - Cholesterol is a major lipid component of the mammalian plasma membrane. While
      much is known about its metabolism, its transport, and its role in
      atherosclerotic vascular disease, less is known about its role in neuronal
      pathophysiology. This study reveals an unexpected function of cholesterol in
      controlling pain transmission. We show that inflammation lowers cholesterol
      content in skin tissue and sensory DRG culture. Pharmacological depletion of
      cellular cholesterol entails sensitization of nociceptive neurons and promotes
      mechanical and thermal hyperalgesia through the activation of voltage-gated
      Nav1.9 channels. Inflammatory mediators enhance the production of reactive oxygen
      species and induce partitioning of Nav1.9 channels from cholesterol-rich lipid
      rafts to cholesterol-poor non-raft regions of the membrane. Low-cholesterol
      environment enhances voltage-dependent activation of Nav1.9 channels leading to
      enhanced neuronal excitability, whereas cholesterol replenishment reversed these
      effects. Consistently, we show that transcutaneous delivery of cholesterol
      alleviates hypersensitivity in animal models of acute and chronic inflammatory
      pain. In conclusion, our data establish that membrane cholesterol is a modulator
      of pain transmission and shed a new light on the relationship between cholesterol
      homeostasis, inflammation, and pain.

PMID- 29459436
TI  - Structure of a eukaryotic cytoplasmic pre-40S ribosomal subunit.
AB  - Final maturation of eukaryotic ribosomes occurs in the cytoplasm and requires the
      sequential removal of associated assembly factors and processing of the immature
      20S pre-RNA Using cryo-electron microscopy (cryo-EM), we have determined the
      structure of a yeast cytoplasmic pre-40S particle in complex with Enp1, Ltv1,
      Rio2, Tsr1, and Pno1 assembly factors poised to initiate final maturation. The
      structure reveals that the pre-rRNA adopts a highly distorted conformation of its
      3' major and 3' minor domains stabilized by the binding of the assembly factors.
      This observation is consistent with a mechanism that involves concerted release
      of the assembly factors orchestrated by the folding of the rRNA in the head of
      the pre-40S subunit during the final stages of maturation. Our results provide a
      structural framework for the coordination of the final maturation events that
      drive a pre-40S particle toward the mature form capable of engaging in
      translation.

PMID- 29459439
TI  - Apalutamide OK'd for Some Prostate Cancers.
AB  - The FDA approved the antiandrogen apalutamide for the treatment of men with
      nonmetastatic, castration-resistant prostate cancer, the first drug for these
      patients greenlighted by the agency. Data from the definitive trial of
      apalutamide, presented at the 2018 Genitourinary Cancers Symposium, showed that
      the drug prolonged metastasis-free survival by more than 2 years compared with
      placebo. Data on the related drug enzalutamide, also presented at the symposium,
      showed that that drug led to dramatic improvements in metastasis-free survival,
      too.

PMID- 29459440
TI  - Correction: ROS1-1.

PMID- 29459437
TI  - LPS targets host guanylate-binding proteins to the bacterial outer membrane for
      non-canonical inflammasome activation.
AB  - Pathogenic and commensal Gram-negative bacteria produce and release outer
      membrane vesicles (OMVs), which present several surface antigens and play an
      important role for bacterial pathogenesis. OMVs also modulate the host immune
      system, which makes them attractive as vaccine candidates. At the cellular level,
      OMVs are internalized by macrophages and deliver lipopolysaccharide (LPS) into
      the host cytosol, thus activating the caspase-11 non-canonical inflammasome.
      Here, we show that OMV-induced inflammasome activation requires TLR4-TRIF
      signaling, the production of type I interferons, and the action of guanylate
      binding proteins (GBPs), both in macrophages and in vivo Mechanistically, we find
      that isoprenylated GBPs associate with the surface of OMVs or with transfected
      LPS, indicating that the key factor that determines GBP recruitment to the Gram
      negative bacterial outer membranes is LPS itself. Our findings provide new
      insights into the mechanism by which GBPs target foreign surfaces and reveal a
      novel function for GBPs in controlling the intracellular detection of LPS derived
      from extracellular bacteria in the form of OMVs, thus extending their function as
      a hub between cell-autonomous immunity and innate immunity.

PMID- 29459442
TI  - What's happening in Neurology(r).

PMID- 29459438
TI  - Non-cell-autonomous function of DR6 in Schwann cell proliferation.
AB  - Death receptor 6 (DR6) is an orphan member of the TNF receptor superfamily and
      controls cell death and differentiation in a cell-autonomous manner in different
      cell types. Here, we report an additional non-cell-autonomous function for DR6 in
      the peripheral nervous system (PNS). DR6-knockout (DR6 KO) mice showed precocious
      myelination in the PNS Using an in vitro myelination assay, we demonstrate that
      neuronal DR6 acts in trans on Schwann cells (SCs) and reduces SC proliferation
      and myelination independently of its cytoplasmic death domain. Mechanistically,
      DR6 was found to be cleaved in neurons by "a disintegrin and metalloprotease 10"
      (ADAM10), releasing the soluble DR6 ectodomain (sDR6). Notably, in the in vitro
      myelination assay, sDR6 was sufficient to rescue the DR6 KO phenotype. Thus, in
      addition to the cell-autonomous receptor function of full-length DR6, the
      proteolytically released sDR6 can unexpectedly also act as a paracrine signaling
      factor in the PNS in a non-cell-autonomous manner during SC proliferation and
      myelination. This new mode of DR6 signaling will be relevant in future attempts
      to target DR6 in disease settings.

PMID- 29459441
TI  - MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted
      mice: are there benefits of endocrine defects?
AB  - Growth hormone (GH) is produced primarily by anterior pituitary somatotroph
      cells. Numerous acute human (h) GH treatment and long-term follow-up studies and
      extensive use of animal models of GH action have shaped the body of GH research
      over the past 70 years. Work on the GH receptor (R)-knockout (GHRKO) mice and
      results of studies on GH-resistant Laron Syndrome (LS) patients have helped
      define many physiological actions of GH including those dealing with metabolism,
      obesity, cancer, diabetes, cognition and aging/longevity. In this review, we have
      discussed several issues dealing with these biological effects of GH and attempt
      to answer the question of whether decreased GH action may be beneficial.

PMID- 29459444
TI  - What's happening in Neurology(r)Genetics.

PMID- 29459443
TI  - What's happening in Neurology(r)Clinical Practice.

PMID- 29459445
TI  - What's happening in Neurology(r)Neuroimmunology & Neuroinflammation.

PMID- 29459446
TI  - Carotid artery stenting with optical coherence tomography.

PMID- 29459447
TI  - Clinical Reasoning: An unusual cause of adult cryptogenic ischemic stroke.

PMID- 29459448
TI  - Editors' note: Upgoing thumb sign: A sensitive indicator of brain involvement?

PMID- 29459451
TI  - Reader response: Upgoing thumb sign: A sensitive indicator of brain involvement?

PMID- 29459449
TI  - Reader response: Upgoing thumb sign: A sensitive indicator of brain involvement?

PMID- 29459450
TI  - Reader response: Upgoing thumb sign: A sensitive indicator of brain involvement?

PMID- 29459452
TI  - Author response: Upgoing thumb sign: A sensitive indicator of brain involvement?

PMID- 29459453
TI  - Upgoing thumb sign: A sensitive indicator of brain involvement.

PMID- 29459454
TI  - Journal Club: MRI reveals acute inflammation in cortical lesions during early MS.
AB  - Early multiple sclerosis is characterized by immune-associated demyelination of
      CNS axons. In a recent Neurology(r) article, Maranzano et al. evaluated MRI scans
      of patients with early multiple sclerosis to study the evolution of leukocortical
      lesions. Their novel data suggest that acute inflammation after blood-brain
      barrier leakage may contribute to gray matter cortical lesions in early multiple
      sclerosis.

PMID- 29459455
TI  - Pearls & Oy-sters: Delayed progression of isolated cortical vein thrombosis
      despite therapeutic INR.

PMID- 29459456
TI  - Teaching Video NeuroImages: Heimann-Bielschowsky phenomenon: A harmless monocular
      nystagmus.

PMID- 29459458
TI  - Second Annual Go Red for Women Issue.

PMID- 29459457
TI  - Tamoxifen Metabolism and Efficacy in Breast Cancer: A Prospective Multicenter
      Trial.
AB  - Purpose: Levels of endoxifen, the most active metabolite of tamoxifen, vary by
      the highly polymorphic cytochrome P450 (CYP) 2D6 enzyme. We prospectively
      investigated tamoxifen efficacy by serum endoxifen levels and the tamoxifen
      activity score (TAS).Experimental Design: A prospective observational multicenter
      study included postmenopausal women with an estrogen receptor-positive breast
      cancer receiving first-line tamoxifen, 20 mg daily in the neoadjuvant or
      metastatic setting, recruited between February 2009 and May 2014. The primary
      endpoint was the objective response rate (ORR) using RECIST criteria 1.0.
      Secondary endpoints were clinical benefit (CB), progression-free survival (PFS),
      and tolerability of tamoxifen. The main analysis used logistic regression to
      relate ORR to serum endoxifen levels after 3 months. Endpoints were also related
      to other tamoxifen metabolites and to TAS.Results: Endoxifen levels were
      available for 247 of all 297 patients (83%), of which 209 with target lesions
      (85%). Median follow-up time for PFS was 32.5 months, and 62% progressed. ORR and
      CB were 45% and 84%, respectively. ORR was not related to endoxifen, and the OR
      of ORR was 1.008 per MUg/L increase in endoxifen (95% confidence interval, 0.971
      1.046; P = 0.56). In general, none of the endpoints was associated with endoxifen
      levels, tamoxifen metabolites, or TAS.Conclusions: Under the prespecified
      assumptions, the results from this prospective clinical trial do not suggest
      therapeutic drug monitoring of endoxifen to be of clinical value in
      postmenopausal women treated with tamoxifen for breast cancer in the neoadjuvant
      or metastatic setting. Clin Cancer Res; 24(10); 2312-8. (c)2018 AACR.

PMID- 29459459
TI  - Redressing the Red Dress: Rethinking the Campaign.

PMID- 29459460
TI  - Poorly Understood Maternal Risks of Pregnancy in Women With Heart Disease.

PMID- 29459461
TI  - Who Resembles a Scientific Leader-Jack or Jill? How Implicit Bias Could Influence
      Research Grant Funding.

PMID- 29459464
TI  - Sauce for the Goose Versus Sauce for the Gander: Should Men and Women Play the
      Same Game But With Different Rules?

PMID- 29459463
TI  - Sex Differences in the Presentation and Perception of Symptoms Among Young
      Patients With Myocardial Infarction: Evidence from the VIRGO Study (Variation in
      Recovery: Role of Gender on Outcomes of Young AMI Patients).
AB  - BACKGROUND: Some studies report that women are less likely to present with chest
      pain for acute myocardial infarction (AMI). Information on symptom presentation,
      perception of symptoms, and care-seeking behaviors is limited for young patients
      with AMI. METHODS: We interviewed 2009 women and 976 men aged 18 to 55 years
      hospitalized for AMI at 103 US hospitals participating in the VIRGO study
      (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients).
      Structured patient interviews during the index AMI hospitalization were used to
      collect information on symptom presentation, perception of symptoms, and care
      seeking behaviors. We compared patient characteristics and presentation
      information by sex. Multivariable hierarchical logistic regression was used to
      evaluate the association between sex and symptom presentation. RESULTS: The
      majority of women (87.0%) and men (89.5%) presented with chest pain (defined as
      pain, pressure, tightness, or discomfort). Women were more likely to present with
      >=3 associated symptoms than men (eg, epigastric symptoms, palpitations, and pain
      or discomfort in the jaw, neck, arms, or between the shoulder blades; 61.9% for
      women versus 54.8% for men, P<0.001). In adjusted analyses, women with an ST
      segment-elevation AMI were more likely than men to present without chest pain
      (odds ratio, 1.51; 95% confidence interval, 1.03-2.22). In comparison with men,
      women were more likely to perceive symptoms as stress/anxiety (20.9% versus
      11.8%, P<0.001) but less likely to attribute symptoms to muscle pain (15.4%
      versus 21.2%, P=0.029). Approximately 29.5% of women and 22.1% of men sought
      medical care for similar symptoms before their hospitalization (P<0.001);
      however, 53% of women reported that their provider did not think these symptoms
      were heart-related in comparison with 37% of men (P<0.001). CONCLUSIONS: The
      presentation of AMI symptoms was similar for young women and men, with chest pain
      as the predominant symptom for both sexes. Women presented with a greater number
      of additional non-chest pain symptoms regardless of the presence of chest pain,
      and both women and their healthcare providers were less likely to attribute their
      prodromal symptoms to heart disease in comparison with men.

PMID- 29459462
TI  - Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical
      Revascularization: Results From the STICH Trial (Surgical Treatment for Ischemic
      Heart Failure).
AB  - BACKGROUND: Female sex is conventionally considered a risk factor for coronary
      artery bypass grafting (CABG) and has been included as a poor prognostic factor
      in multiple cardiac operative risk evaluation scores. We aimed to investigate the
      association of sex and the long-term benefit of CABG in patients with ischemic
      left ventricular dysfunction enrolled in the prospective STICH trial (Surgical
      Treatment for Ischemic Heart Failure Study). METHODS: The STICH trial randomized
      1212 patients (148 [12%] women and 1064 [88%] men) with coronary artery disease
      and left ventricular ejection fraction <=35% to CABG+medical therapy (MED) versus
      MED alone. Long-term (10-year) outcomes with each treatment were compared
      according to sex. RESULTS: At baseline, women were older (63.4 versus 59.3 years;
      P=0.016) with higher body mass index (27.9 versus 26.7 kg/m2; P=0.001). Women had
      more coronary artery disease risk factors (diabetes mellitus, 55.4% versus 37.2%;
      hypertension, 70.9% versus 58.6%; hyperlipidemia, 70.3% versus 58.9%) except for
      smoking (13.5% versus 21.8%) and had lower rates of prior CABG (0% versus 3.4%;
      all P<0.05) than men. Moreover, women had higher New York Heart Association class
      (class III/IV, 66.2% versus 57.0%), lower 6-minute walk capacity (300 versus 350
      m), and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (51
      versus 63; all P<0.05). Over 10 years of follow-up, all-cause mortality (49.0%
      versus 65.8%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.52-0.86;
      P=0.002) and cardiovascular mortality (34.3% versus 52.3%; adjusted hazard ratio,
      0.65; 95% confidence interval, 0.48-0.89; P=0.006) were significantly lower in
      women compared with men. With randomization to CABG+MED versus MED treatment,
      there was no significant interaction between sex and treatment group in all-cause
      mortality, cardiovascular mortality, or the composite of all-cause mortality or
      cardiovascular hospitalization (all P>0.05). In addition, surgical deaths were
      not statistically different (1.5% versus 5.1%; P=0.187) between sexes among
      patients randomized to CABG per protocol as initial treatment. CONCLUSIONS: Sex
      is not associated with the effect of CABG+MED versus MED on all-cause mortality,
      cardiovascular mortality, the composite of death or cardiovascular
      hospitalization, or surgical deaths in patients with ischemic left ventricular
      dysfunction. Thus, sex should not influence treatment decisions about CABG in
      these patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov.
      Unique identifier: NCT00023595.

PMID- 29459466
TI  - Pregnancy Outcomes in Women With Rheumatic Mitral Valve Disease: Results From the
      Registry of Pregnancy and Cardiac Disease.
AB  - BACKGROUND: Cardiac disease is 1 of the major causes of maternal mortality. We
      studied pregnancy outcomes in women with rheumatic mitral valve disease. METHODS:
      The Registry of Pregnancy and Cardiac Disease is an international prospective
      registry, and consecutive pregnant women with cardiac disease were included.
      Pregnancy outcomes in all women with rheumatic mitral valve disease and no
      prepregnancy valve replacement is described in the present study (n=390). A
      maternal cardiac event was defined as cardiac death, arrhythmia requiring
      treatment, heart failure, thromboembolic event, aortic dissection, endocarditis,
      acute coronary syndrome, and hospitalization for other cardiac reasons or cardiac
      intervention. Associations between patient characteristics and cardiac outcomes
      were checked in a 3-level model (patient-center-country). RESULTS: Most patients
      came from emerging countries (75%). Mitral stenosis (MS) with or without mitral
      regurgitation (MR) was present in 273 women, isolated MR in 117. The degree of MS
      was mild in 20.9%, moderate in 39.2%, severe in 19.8%, and severity not
      classified in the remainder. Maternal death during pregnancy occurred in 1
      patient with severe MS. Hospital admission occurred in 23.1% of the women with
      MS, and the main reason was heart failure (mild MS 15.8%, moderate 23.4%, severe
      48.1%; P<0.001). Heart failure occurred in 23.1% of patients with moderate or
      severe MR. An intervention during pregnancy was performed in 16 patients, 14 had
      percutaneous balloon mitral commissurotomy, and 2 had surgical valve replacement
      (1 for MS, 1 for MR). In multivariable modeling, prepregnancy New York Heart
      Association class >1 was an independent predictor of maternal cardiac events.
      Follow-up at 6 months postpartum was available for 53%, and 3 more patients died
      (1 with severe MS, 1 with moderate MS, 1 with moderate to severe MR).
      CONCLUSIONS: Although mortality was only 1.9% during pregnancy, ~50% of the
      patients with severe rheumatic MS and 23% of those with significant MR developed
      heart failure during pregnancy. Prepregnancy counseling and considering mitral
      valve interventions in selected patients are important to prevent these
      complications.

PMID- 29459465
TI  - Mental Stress-Induced-Myocardial Ischemia in Young Patients With Recent
      Myocardial Infarction: Sex Differences and Mechanisms.
AB  - BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is frequent in
      patients with coronary artery disease and is associated with worse prognosis.
      Young women with a previous myocardial infarction (MI), a group with unexplained
      higher mortality than men of comparable age, have shown elevated rates of MSIMI,
      but the mechanisms are unknown. METHODS: We studied 306 patients (150 women and
      156 men) <=61 years of age who were hospitalized for MI in the previous 8 months
      and 112 community controls (58 women and 54 men) frequency matched for sex and
      age to the patients with MI. Endothelium-dependent flow-mediated dilation and
      microvascular reactivity (reactive hyperemia index) were measured at rest and 30
      minutes after mental stress. The digital vasomotor response to mental stress was
      assessed using peripheral arterial tonometry. Patients received 99mTc-sestamibi
      myocardial perfusion imaging at rest, with mental (speech task) and conventional
      (exercise/pharmacological) stress. RESULTS: The mean age of the sample was 50
      years (range, 22-61). In the MI group but not among controls, women had a more
      adverse socioeconomic and psychosocial profile than men. There were no sex
      differences in cardiovascular risk factors, and among patients with MI, clinical
      severity tended to be lower in women. Women in both groups showed a higher
      peripheral arterial tonometry ratio during mental stress but a lower reactive
      hyperemia index after mental stress, indicating enhanced microvascular
      dysfunction after stress. There were no sex differences in flow-mediated dilation
      changes with mental stress. The rate of MSIMI was twice as high in women as in
      men (22% versus 11%, P=0.009), and ischemia with conventional stress was
      similarly elevated (31% versus 16%, P=0.002). Psychosocial and clinical risk
      factors did not explain sex differences in inducible ischemia. Although vascular
      responses to mental stress (peripheral arterial tonometry ratio and reactive
      hyperemia index) also did not explain sex differences in MSIMI, they were
      predictive of MSIMI in women only. CONCLUSIONS: Young women after MI have a 2
      fold likelihood of developing MSIMI compared with men and a similar increase in
      conventional stress ischemia. Microvascular dysfunction and peripheral
      vasoconstriction with mental stress are implicated in MSIMI among women but not
      among men, perhaps reflecting women's proclivity toward ischemia because of
      microcirculatory abnormalities.

PMID- 29459467
TI  - Rheumatic Heart Disease in Pregnancy: Global Challenges and Clear Opportunities.

PMID- 29459468
TI  - Genetics, Lifestyle, and Low-Density Lipoprotein Cholesterol in Young and
      Apparently Healthy Women.
AB  - BACKGROUND: Atherosclerosis starts in childhood but low-density lipoprotein
      cholesterol (LDL-C), a causal risk factor, is mostly studied and dealt with when
      clinical events have occurred. Women are usually affected later in life than men
      and are underdiagnosed, undertreated, and understudied in cardiovascular trials
      and research. This study aims at a better understanding of lifestyle and genetic
      factors that affect LDL-C in young women. METHODS: We randomly selected for every
      year of age 8 women with LDL-C <=1st percentile (<=50 mg/dL) and 8 women with LDL
      C >=99th percentile (>=186 mg/dL) from 28 000 female participants aged between 25
      to 40 years of a population-based cohort study. The resulting groups include 119
      and 121 women, respectively, of an average 33 years of age. A gene-sequencing
      panel was used to assess established monogenic and polygenic origins of these
      phenotypes. Information on lifestyle was extracted from questionnaires. A healthy
      lifestyle score was allocated based on a recently developed algorithm. RESULTS:
      Of the women with LDL-C <=1st percentile, 19 (15.7%) carried mutations that are
      causing monogenic hypocholesterolemia and 60 (49.6%) were genetically predisposed
      to low LDL-C on the basis of an extremely low weighted genetic risk score. In
      comparison with control groups, a healthier lifestyle was not associated with low
      LDL-C in women without genetic predispositions. Among women with LDL-C >=99th
      percentile, 20 women (16.8%) carried mutations that cause familial
      hypercholesterolemia, whereas 25 (21%) were predisposed to high LDL-C on the
      basis of a high-weighted genetic risk score. The women in whom no genetic origin
      for hypercholesterolemia could be identified were found to exhibit a
      significantly unfavorable lifestyle in comparison with controls. CONCLUSIONS:
      This study highlights the need for early assessment of the cardiovascular risk
      profile in apparently healthy young women to identify those with LDL-C >=99th
      percentile for their age: first, because, in this study, 17% of the cases were
      molecularly diagnosed with familial hypercholesterolemia, which needs further
      attention; second, because our data indicate that an unfavorable lifestyle is
      significantly associated with severe hypercholesterolemia in genetically
      unaffected women, which may also need further attention.

PMID- 29459469
TI  - Female Sex Is a Risk Modifier Rather Than a Risk Factor for Stroke in Atrial
      Fibrillation: Should We Use a CHA2DS2-VA Score Rather Than CHA2DS2-VASc?
AB  - BACKGROUND: Stroke risk in atrial fibrillation is assessed by using the CHA2DS2
      VASc score. Sex category (Sc, ie, female sex) confers 1 point on CHA2DS2-VASc. We
      hypothesized that female sex is a stroke risk modifier, rather than an overall
      risk factor, when added to a CHA2DS2-VA (sex-independent thromboembolism risk)
      score scale. METHODS: Using 3 nationwide registries, we identified patients with
      incident nonvalvular atrial fibrillation from January 1, 1997, through December
      31, 2015. Patients receiving oral anticoagulant treatment at baseline were
      excluded, and person-time was censored at the time of treatment initiation (if
      any). CHA2DS2-VA scores were calculated for men and women, and were followed for
      up to 1 year in the Danish National Patient Registry. The primary outcome was a
      primary hospital code for ischemic stroke or systemic embolism (thromboembolism).
      We calculated crude event rates for risk strata as events per 100 person-years.
      For quantifying absolute risk of stroke, we calculated risks based on the
      pseudovalue method. Female sex as a prognostic factor was investigated by
      inclusion as an interaction term on the CHA2DS2-VA score to calculate the
      thromboembolic risk ratio for different score points. RESULTS: A total of 239 671
      patients with atrial fibrillation (48.7% women) contributed to the analyses. The
      mean ages for women and men were 76.6 years and 70.3 years, respectively; the
      mean CHA2DS2-VA scores were 2.7 for women and 2.3 for men. The overall 1-year
      thromboembolic rate per 100 person-years for women was 7.3 and 5.7 for men. The 1
      year absolute risk of thromboembolism was 0.5% among men and women with a CHA2DS2
      VA score of 0 and increased up to >7% among very comorbid patients (score >5).
      The risk ratio (male as reference) across points >1 indicated that women exhibit
      a higher stroke risk. The interaction was statistically significant (P<0.001).
      CONCLUSIONS: Female sex is a risk modifier for stroke in patients with atrial
      fibrillation. Initial decisions on oral anticoagulant treatment could be guided
      by a CHA2DS2-VA score (ie, excluding the sex category criterion), but the Sc risk
      component modifies and accentuates stroke risk in women who would have been
      eligible for oral anticoagulant treatment on the basis of >=2 additional stroke
      risk factors.

PMID- 29459470
TI  - Metabolic Predictors of Incident Coronary Heart Disease in Women.
AB  - BACKGROUND: Although metabolomic profiling offers promise for the prediction of
      coronary heart disease (CHD), and metabolic risk factors are more strongly
      associated with CHD in women than men, limited data are available for women.
      METHODS: We applied a liquid chromatography-tandem mass spectrometry metabolomics
      platform to measure 371 metabolites in a discovery set of postmenopausal women
      (472 incident CHD cases, 472 controls) with validation in an independent set of
      postmenopausal women (312 incident CHD cases, 315 controls). RESULTS: Eight
      metabolites, primarily oxidized lipids, were significantly dysregulated in cases
      after the adjustment for matching and CHD risk factors in both the discovery and
      validation data sets. One oxidized phospholipid, C34:2 hydroxy
      phosphatidylcholine, remained associated with CHD after further adjustment for
      other validated metabolites. Subjects with C34:2 hydroxy-phosphatidylcholine
      levels in the highest quartile had a 4.7-fold increase in CHD odds in comparison
      with the lowest quartile; C34:2 hydroxy-phosphatidylcholine also significantly
      improved the area under the curve (P<0.01) for CHD. The C34:2 hydroxy
      phosphatidylcholine findings were replicated in a third replication data set of
      980 men and women (230 cardiovascular events) with a stronger association
      observed in women. CONCLUSIONS: These data replicate known metabolite predictors,
      identify novel markers, and support the relationship between lipid oxidation and
      subsequent CHD.

PMID- 29459471
TI  - Gender/Sex as a Social Determinant of Cardiovascular Risk.
AB  - The social gradient for cardiovascular disease (CVD) onset and outcomes is well
      established. The American Heart Association's Social Determinants of Risk and
      Outcomes of Cardiovascular Disease Scientific Statement advocates looking beyond
      breakthroughs in biological science toward a social determinants approach that
      focuses on socioeconomic position, race and ethnicity, social support, culture
      and access to medical care, and residential environments to curb the burden of
      CVD going forward. Indeed, the benefits of this approach are likely to be far
      reaching, enhancing the positive effects of advances in CVD related to prevention
      and treatment while reducing health inequities that contribute to CVD onset and
      outcomes. It is disappointing that the role of gender has been largely neglected
      despite being a critical determinant of cardiovascular health. It is clear that
      trajectories and outcomes of CVD differ by biological sex, yet the tendency for
      sex and gender to be conflated has contributed to the idea that both are constant
      or fixed with little room for intervention. Rather, as distinct from biological
      sex, gender is socially produced. Overlaid on biological sex, gender is a broad
      term that shapes and interacts with one's cognition to guide norms, roles,
      behaviors, and social relations. It is a fluid construct that varies across time,
      place, and life stage. Gender can interact with biological sex and, indeed, other
      social determinants, such as ethnicity and socioeconomic position, to shape
      cardiovascular health from conception, through early life when health behaviors
      and risk factors are shaped, into adolescence and adulthood. This article will
      illustrate how gender shapes the early adoption of health behaviors in childhood,
      adolescence, and young adulthood by focusing on physical activity, drinking, and
      smoking behaviors (including the influence of role modeling). We will also
      discuss the role of gender in psychosocial stress with a focus on trauma from
      life events (childhood assault and intimate partner violence) and work, home, and
      financial stresses. We conclude by exploring potential biological pathways, with
      a focus on autonomic functioning, which may underpin gender as a social
      determinant of cardiovascular health. Finally, we discuss implications for
      cardiovascular treatment and awareness campaigns and consider whether gender
      equality strategies could reduce the burden of CVD for men and women at the
      population level.

PMID- 29459473
TI  - Women Not Receiving Optimal Preventive Medications.

PMID- 29459472
TI  - Association of Spontaneous Preterm Delivery and Future Maternal Cardiovascular
      Disease.
AB  - Cardiovascular disease (CVD) risk factors are well established. However, little
      is known about a woman's cardiovascular response to pregnancy, which appears to
      be an early marker of future maternal CVD risk. Spontaneous preterm delivery
      (sPTD) has been associated with a <=3-fold increased risk of maternal CVD death
      later in life compared with having a term delivery. This review focuses on 3 key
      areas to critically assess the association of sPTD and future maternal CVD risk:
      (1) CVD risk factors, (2) inflammatory biomarkers of interest, and (3) specific
      forms of vascular dysfunction, such as endothelial function and arterial
      stiffness, and mechanisms by which each may be linked to sPTD. The association of
      sPTD with subsequent future maternal CVD risk suggests that a woman's abnormal
      response to pregnancy may serve as her first physiological stress test. These
      findings suggest that future research is needed to understand why women with sPTD
      may be at risk for CVD to implement effective interventions earlier in a woman's
      life.

PMID- 29459474
TI  - Myocardial Scar Is Prevalent and Associated With Subclinical Myocardial
      Dysfunction in Women With Suspected Ischemia But No Obstructive Coronary Artery
      Disease: From the Women's Ischemia Syndrome Evaluation-Coronary Vascular
      Dysfunction Study.

PMID- 29459475
TI  - Prevalence of Subclinical Coronary Artery Disease Assessed by Coronary Computed
      Tomography Angiography in 45- to 55-Year-Old Women With a History of
      Preeclampsia.

PMID- 29459476
TI  - Long-Term Analysis of Sex Differences in Prestigious Authorships in
      Cardiovascular Research Supported by the National Institutes of Health.

PMID- 29459477
TI  - Intrinsic Functional Potential of NK-Cell Subsets Constrains Retargeting Driven
      by Chimeric Antigen Receptors.
AB  - Natural killer (NK) cells hold potential as a source of allogeneic cytotoxic
      effector cells for chimeric antigen receptor (CAR)-mediated therapies. Here, we
      explored the feasibility of transfecting CAR-encoding mRNA into primary NK cells
      and investigated how the intrinsic potential of discrete NK-cell subsets affects
      retargeting efficiency. After screening five second- and third-generation anti
      CD19 CAR constructs with different signaling domains and spacer regions, a third
      generation CAR with the CH2-domain removed was selected based on its expression
      and functional profiles. Kinetics experiments revealed that CAR expression was
      optimal after 3 days of IL15 stimulation prior to transfection, consistently
      achieving over 80% expression. CAR-engineered NK cells acquired increased
      degranulation toward CD19+ targets, and maintained their intrinsic degranulation
      response toward CD19- K562 cells. The response of redirected NK-cell subsets
      against CD19+ targets was dependent on their intrinsic thresholds for activation
      determined through both differentiation and education by killer cell
      immunoglobulin-like receptors (KIR) and/or CD94/NKG2A binding to self HLA class I
      and HLA-E, respectively. Redirected primary NK cells were insensitive to
      inhibition through NKG2A/HLA-E interactions but remained sensitive to inhibition
      through KIR depending on the amount of HLA class I expressed on target cells.
      Adaptive NK cells, expressing NKG2C, CD57, and self-HLA-specific KIR(s),
      displayed superior ability to kill CD19+, HLA low, or mismatched tumor cells.
      These findings support the feasibility of primary allogeneic NK cells for CAR
      engineering and highlight a need to consider NK-cell diversity when optimizing
      efficacy of cancer immunotherapies based on CAR-expressing NK cells. Cancer
      Immunol Res; 6(4); 467-80. (c)2018 AACR.

PMID- 29459479
TI  - The new chest x ray.

PMID- 29459478
TI  - Targeting Cytokine Therapy to the Pancreatic Tumor Microenvironment Using PD-L1
      Specific VHHs.
AB  - Cytokine-based therapies for cancer have not achieved widespread clinical success
      because of inherent toxicities. Treatment for pancreatic cancer is limited by the
      dense stroma that surrounds tumors and by an immunosuppressive tumor
      microenvironment. To overcome these barriers, we developed constructs of single
      domain antibodies (VHHs) against PD-L1 fused with IL-2 and IFNgamma. Targeting
      cytokine delivery in this manner reduced pancreatic tumor burden by 50%, whereas
      cytokines fused to an irrelevant VHH, or blockade of PD-L1 alone, showed little
      effect. Targeted delivery of IL-2 increased the number of intratumoral CD8+ T
      cells, whereas IFNgamma reduced the number of CD11b+ cells and skewed
      intratumoral macrophages toward the display of M1-like characteristics. Imaging
      of fluorescent VHH-IFNgamma constructs, as well as transcriptional profiling,
      demonstrated targeting of IFNgamma to the tumor microenvironment. Many tumors and
      tumor-infiltrating myeloid cells express PD-L1, rendering them potentially
      susceptible to this form of targeted immunotherapy. Cancer Immunol Res; 6(4); 389
      401. (c)2018 AACR.

PMID- 29459480
TI  - Occupational exposure to pesticides is associated with differential DNA
      methylation.
AB  - OBJECTIVES: Occupational pesticide exposure is associated with a wide range of
      diseases, including lung diseases, but it is largely unknown how pesticides
      influence airway disease pathogenesis. A potential mechanism might be through
      epigenetic mechanisms, like DNA methylation. Therefore, we assessed associations
      between occupational exposure to pesticides and genome-wide DNA methylation
      sites. METHODS: 1561 subjects of LifeLines were included with either no (n=1392),
      low (n=108) or high (n=61) exposure to any type of pesticides (estimated based on
      current or last held job). Blood DNA methylation levels were measured using
      Illumina 450K arrays. Associations between pesticide exposure and 420 938
      methylation sites (CpGs) were assessed using robust linear regression adjusted
      for appropriate confounders. In addition, we performed genome-wide stratified and
      interaction analyses by gender, smoking and airway obstruction status, and
      assessed associations between gene expression and methylation for genome-wide
      significant CpGs (n=2802). RESULTS: In total for all analyses, high pesticide
      exposure was genome-wide significantly (false discovery rate P<0.05) associated
      with differential DNA methylation of 31 CpGs annotated to 29 genes. Twenty of
      these CpGs were found in subjects with airway obstruction. Several of the
      identified genes, for example, RYR1, ALLC, PTPRN2, LRRC3B, PAX2 and VTRNA2-1, are
      genes previously linked to either pesticide exposure or lung-related diseases.
      Seven out of 31 CpGs were associated with gene expression levels. CONCLUSIONS: We
      show for the first time that occupational exposure to pesticides is genome-wide
      associated with differential DNA methylation. Further research should reveal
      whether this differential methylation plays a role in the airway disease
      pathogenesis induced by pesticides.

PMID- 29459482
TI  - Where does public funding for cancer research go: Allocation of research funding
      for cancer and COPD is not always proportional to disease burden.

PMID- 29459481
TI  - Catalytic activities of mammalian epoxide hydrolases with cis and trans fatty
      acid epoxides relevant to skin barrier function.
AB  - Lipoxygenase (LOX)-catalyzed oxidation of the essential fatty acid, linoleate,
      represents a vital step in construction of the mammalian epidermal permeability
      barrier. Analysis of epidermal lipids indicates that linoleate is converted to a
      trihydroxy derivative by hydrolysis of an epoxy-hydroxy precursor. We evaluated
      different epoxide hydrolase (EH) enzymes in the hydrolysis of skin-relevant fatty
      acid epoxides and compared the products to those of acid-catalyzed hydrolysis. In
      the absence of enzyme, exposure to pH 5 or pH 6 at 37 degrees C for 30 min
      hydrolyzed fatty acid allylic epoxyalcohols to four trihydroxy products. By
      contrast, human soluble EH [sEH (EPHX2)] and human or murine epoxide hydrolase-3
      [EH3 (EPHX3)] hydrolyzed cis or trans allylic epoxides to single diastereomers,
      identical to the major isomers detected in epidermis. Microsomal EH [mEH (EPHX1)]
      was inactive with these substrates. At low substrate concentrations (<10 MUM),
      EPHX2 hydrolyzed 14,15-epoxyeicosatrienoic acid (EET) at twice the rate of the
      epidermal epoxyalcohol, 9R,10R-trans-epoxy-11E-13R-hydroxy-octadecenoic acid,
      whereas human or murine EPHX3 hydrolyzed the allylic epoxyalcohol at 31-fold and
      39-fold higher rates, respectively. These data implicate the activities of EPHX2
      and EPHX3 in production of the linoleate triols detected as end products of the
      12R-LOX pathway in the epidermis and implicate their functioning in formation of
      the mammalian water permeability barrier.

PMID- 29459483
TI  - Dihydrofolate reductase and membrane translocation: evolution of a classic
      experiment: Classic landmark papers, irrespective of their age, can teach
      students how best science is practiced and inspire new experiments.

PMID- 29459484
TI  - When TRBP leaves Dicer at the alt-'ER.

PMID- 29459485
TI  - p13 protects against Parkinson's disease.

PMID- 29459487
TI  - Trimming it short: PNLDC1 is required for piRNA maturation during mouse
      spermatogenesis.

PMID- 29459488
TI  - Development of clinical sign-based scoring system for assessment of omphalitis in
      neonatal calves.
AB  - Omphalitis contributes significantly to morbidity and mortality in neonatal
      calves. Diagnosis of omphalitis is based on the local signs of inflammation-pain,
      swelling, local heat and purulent discharge. An abattoir trial identified an
      optimal, sign-based, scoring system for diagnosis of omphalitis. A sample of 187
      calves aged between 7 and 15 days old were clinically examined for signs of
      umbilical inflammation and compared with postmortem examination of navels. On
      postmortem findings, 64 calves (34.2 per cent) had omphalitis. In the examined
      omphalitis cases, the most commonly affected umbilical structure was the urachus
      (78.1 per cent). Multivariable logistic regression revealed that thickening of
      the umbilical stump over 1.3 cm (P<0.001), discharge (P<0.001), raised local
      temperature (P=0.003) and the presence of umbilical hernia (P=0.024) were
      correlated and positive predictors of omphalitis. Discharge from the umbilical
      stump was associated with intra-abdominal inflammation (P=0.004). Assigning
      weights based on the multivariable logistic regression coefficients, a clinical
      scoring algorithm was developed. The cumulative score ranged from 0 to 9. Using
      this scoring system, calves were categorised as positive if their total score was
      >=2. This scoring method had a sensitivity of 85.9 per cent, specificity of 74.8
      per cent and correctly classified 78.6 per cent of all calves.

PMID- 29459489
TI  - Fifteen-month duration of immunity for the serovar Grippotyphosa fraction of a
      tetravalent canine leptospirosis vaccine.
AB  - Forty-four specific pathogen-free beagles, median age 65 days, received two
      subcutaneous doses of either a commercially available, five-way combination
      vaccine or the same vaccine in combination with a tetravalent Leptospira bacterin
      (Canicola, Grippotyphosa, Icterohaemorrhagiae, Pomona). They were subsequently
      challenged with a pathogenic strain L kirschneri serovar Grippotyphosa 470 days
      following completion of the vaccination protocol. Titres of agglutinating serum
      antibodies were determined at various time points before and after both
      vaccination and challenge, along with postchallenge reisolation of the challenge
      organisms from blood and urine, and evaluation of renal histopathology. Clinical
      signs of generalised leptospirosis were not observed in any of the dogs after
      challenge. In order to demonstrate efficacy, leptospirosis was defined as having
      at least one positive urine sample and a positive renal histopathology score; or,
      in the absence of renal pathology, multiple positive urine samples. Leptospiremia
      was not demonstrated in any of the vaccinated dogs versus 27 per cent of the
      controls; leptospiruria was noted in 5 per cent of the vaccinates compared with
      76 per cent of controls; and renal lesions were observed in 15 per cent of the
      vaccinates and 65 per cent controls. Using these criteria, the vaccine was able
      to significantly prevent leptospirosis (P=0.0001) in the vaccinated animals. This
      study establishes duration of immunity of at least 15 months for the prevention
      of disease and renal excretion of leptospires for the Leptospira serovar
      Grippotyphosa fraction of a quadrivalent Leptospira vaccine.

PMID- 29459486
TI  - Perturbing mitosis for anti-cancer therapy: is cell death the only answer?
AB  - Interfering with mitosis for cancer treatment is an old concept that has proven
      highly successful in the clinics. Microtubule poisons are used to treat patients
      with different types of blood or solid cancer since more than 20 years, but how
      these drugs achieve clinical response is still unclear. Arresting cells in
      mitosis can promote their demise, at least in a petri dish. Yet, at the molecular
      level, this type of cell death is poorly defined and cancer cells often find ways
      to escape. The signaling pathways activated can lead to mitotic slippage, cell
      death, or senescence. Therefore, any attempt to unravel the mechanistic action of
      microtubule poisons will have to investigate aspects of cell cycle control, cell
      death initiation in mitosis and after slippage, at single-cell resolution. Here,
      we discuss possible mechanisms and signaling pathways controlling cell death in
      mitosis or after escape from mitotic arrest, as well as secondary consequences of
      mitotic errors, particularly sterile inflammation, and finally address the
      question how clinical efficacy of anti-mitotic drugs may come about and could be
      improved.

PMID- 29459490
TI  - Margaret McCartney: Do we want an NHS that depends on outsourcing?

PMID- 29459491
TI  - SULFATION PATHWAYS: Alternate steroid sulfation pathways targeted by LC-MS/MS
      analysis of disulfates: application to prenatal diagnosis of steroid synthesis
      disorders.
AB  - The steroid disulfates (aka bis-sulfates) are a significant but minor fraction of
      the urinary steroid metabolome that have not been widely studied because major
      components are not hydrolyzed by the commercial sulfatases commonly used in
      steroid metabolomics. In early studies, conjugate fractionation followed by
      hydrolysis using acidified solvent (solvolysis) was used for the indirect
      detection of this fraction by GC-MS. This paper describes the application of a
      specific LC-MS/MS method for the direct identification of disulfates in urine,
      and their use as markers for the prenatal diagnosis of disorders causing reduced
      estriol production: STSD (steroid sulfatase deficiency), SLOS (Smith-Lemli-Opitz
      syndrome) and PORD (P450 oxidoreductase deficiency). Disulfates were detected by
      monitoring a constant ion loss (CIL) from the molecular di-anion. While focused
      on disulfates, our methodology included an analysis of intact steroid
      glucuronides and monosulfates because steroidogenic disorder diagnosis usually
      requires an examination of the complete steroid profile. In the disorders
      studied, a few individual steroids (as disulfates) were found particularly
      informative: pregn-5-ene-3beta,20S-diol, pregn-5-ene-3beta,21-diol (STSD,
      neonatal PORD) and 5alpha-pregnane-3beta,20S-diol (pregnancy PORD). Authentic
      steroid disulfates were synthesized for use in this study as aid to
      characterization. Tentative identification of 5xi-pregn-7-ene-3xi,20S-diol and
      5xi-pregn-7-ene-3xi,17,20S-triol disulfates was also obtained in samples from
      SLOS affected pregnancies. Seven ratios between the detected metabolites were
      applied to distinguish the three selected disorders from control samples. Our
      results show the potential of the direct detection of steroid conjugates in the
      diagnosis of pathologies related with steroid biosynthesis.

PMID- 29459492
TI  - "Tragedy" of 35 deaths from measles in Europe last year is unacceptable, says
      WHO.

PMID- 29459493
TI  - Diagnostic strategy in segmentation defect of the vertebrae: a retrospective
      study of 73 patients.
AB  - BACKGROUND: Segmentation defects of the vertebrae (SDV) are non-specific features
      found in various syndromes. The molecular bases of SDV are not fully elucidated
      due to the wide range of phenotypes and classification issues. The genes involved
      are in the Notch signalling pathway, which is a key system in somitogenesis. Here
      we report on mutations identified in a diagnosis cohort of SDV. We focused on
      spondylocostal dysostosis (SCD) and the phenotype of these patients in order to
      establish a diagnostic strategy when confronted with SDV. PATIENTS AND METHODS:
      We used DNA samples from a cohort of 73 patients and performed targeted
      sequencing of the five known SCD-causing genes (DLL3, MESP2, LFNG, HES7 and TBX6)
      in the first 48 patients and whole-exome sequencing (WES) in 28 relevant
      patients. RESULTS: Ten diagnoses, including four biallelic variants in TBX6, two
      biallelic variants in LFNG and DLL3, and one in MESP2 and HES7, were made with
      the gene panel, and two diagnoses, including biallelic variants in FLNB and one
      variant in MEOX1, were made by WES. The diagnostic yield of the gene panel was
      10/73 (13.7%) in the global cohort but 8/10 (80%) in the subgroup meeting the SCD
      criteria; the diagnostic yield of WES was 2/28 (8%). CONCLUSION: After negative
      array CGH, targeted sequencing of the five known SCD genes should only be
      performed in patients who meet the diagnostic criteria of SCD. The low proportion
      of candidate genes identified by WES in our cohort suggests the need to consider
      more complex genetic architectures in cases of SDV.

PMID- 29459495
TI  - Aplastic Anemia and Risk of Incident Atrial Fibrillation - A Nationwide Cohort
      Study.
AB  - BACKGROUND: This retrospective cohort study sought to follow up patients with
      aplastic anemia (AA) to evaluate their risk of developing atrial fibrillation
      (AF).Methods and Results:From the National Health Insurance Research Database of
      Taiwan, this study identified an AA cohort (n=3,921), a general population cohort
      (n=17,617,843) and a propensity score-matched none AA cohort (PSM non-AA cohort
      in brief, n=15,684) in 2000-2010. By the end of 2011, the incident AF was higher
      in the AA cohort than in the general population and PSM non-AA cohorts (8.94 vs.
      1.14 and 6.47 per 1,000 person-years, respectively). The adjusted hazards ratio
      of AF for the AA cohort was 2.12 (95% confidence interval 1.46-3.08) compared
      with the PSM non-AA cohort, after controlling for covariates. However, after
      further controlling for the competing risk of death, adjusted subhazard ratio was
      1.21 (95% CI 0.97-1.50). Among those who developed AF, the AA cohort had a higher
      mortality rate (83.7 vs. 51.1 per 100), but a lower rate of incident stroke (26.0
      vs. 41.5 per 100), compared with the PSM non-AA cohort. CONCLUSIONS: Patients
      with AA could have an elevated risk for AF. The mortality risk increased further
      for those who develop AF.

PMID- 29459494
TI  - A dual-mode hemispherical sparse array for 3D passive acoustic mapping and skull
      localization within a clinical MRI guided focused ultrasound device.
AB  - Previous work has demonstrated that passive acoustic imaging may be used
      alongside MRI for monitoring of focused ultrasound therapy. However, past
      implementations have generally made use of either linear arrays originally
      designed for diagnostic imaging or custom narrowband arrays specific to in-house
      therapeutic transducer designs, neither of which is fully compatible with
      clinical MR-guided focused ultrasound (MRgFUS) devices. Here we have designed an
      array which is suitable for use within an FDA-approved MR-guided transcranial
      focused ultrasound device, within the bore of a 3 Tesla clinical MRI scanner. The
      array is constructed from 5  *  0.4 mm piezoceramic disc elements arranged in
      pseudorandom fashion on a low-profile laser-cut acrylic frame designed to fit
      between the therapeutic elements of a 230 kHz InSightec ExAblate 4000 transducer.
      By exploiting thickness and radial resonance modes of the piezo discs the array
      is capable of both B-mode imaging at 5 MHz for skull localization, as well as
      passive reception at the second harmonic of the therapy array for detection of
      cavitation and 3D passive acoustic imaging. In active mode, the array was able to
      perform B-mode imaging of a human skull, showing the outer skull surface with
      good qualitative agreement with MR imaging. Extension to 3D showed the array was
      able to locate the skull within  +/-2 mm/2 degrees  of reference points derived
      from MRI, which could potentially allow registration of a patient to the therapy
      system without the expense of real-time MRI. In passive mode, the array was able
      to resolve a point source in 3D within a  +/-10 mm region about each axis from
      the focus, detect cavitation (SNR ~ 12 dB) at burst lengths from 10 cycles to
      continuous wave, and produce 3D acoustic maps in a flow phantom. Finally, the
      array was used to detect and map cavitation associated with microbubble activity
      in the brain in nonhuman primates.

PMID- 29459496
TI  - Rare Case of Giant Non-Thrombosed Coronary Artery Aneurysm at the Left Anterior
      Descending Coronary Artery.

PMID- 29459497
TI  - Percutaneous Pulmonary Valve Implantation Contraindicated by Severe Aortic
      Regurgitation Due to Left Coronary Sinus Deformation.

PMID- 29459498
TI  - Evaluation of Suppressiveness of Soils Exhibiting Soil-Borne Disease Suppression
      after Long-Term Application of Organic Amendments by the Co-cultivation Method of
      Pathogenic Fusarium oxysporum and Indigenous Soil Microorganisms.
AB  - Preventive measures against soil-borne diseases need to be implemented before
      cultivation because very few countermeasures are available after the development
      of diseases. Some soils suppress soil-borne diseases despite the presence of a
      high population density of pathogens. If the suppressiveness of soil against soil
      borne diseases may be predicted and diagnosed for crop fields, it may be possible
      to reduce the labor and cost associated with excessive disinfection practices. We
      herein evaluated the suppressiveness of soils in fields with the long-term
      application of organic amendments by examining the growth of pathogenic Fusarium
      oxysporum co-cultivated with indigenous soil microorganisms on agar plates. Soils
      treated with coffee residue compost or rapeseed meal showed suppressiveness
      against spinach wilt disease by F. oxysporum f. sp. spinaciae or spinach wilt and
      lettuce root rot diseases by F. oxysporum f. sp. spinaciae and F. oxysporum f.
      sp. lactucae, respectively, and the growth of pathogenic Fusarium spp. on agar
      plates was suppressed when co-cultured with microorganisms in a suspension from
      these soils before crop cultivation. These results indicate the potential of the
      growth degree of pathogenic F. oxysporum estimated by this method as a diagnostic
      indicator of the suppressiveness of soil associated with the inhabiting
      microorganisms. A correlation was found between the incidence of spinach wilt
      disease in spinach and the growth degree of F. oxysporum f. sp. spinaciae by this
      co-cultivation method, indicating that suppressiveness induced by organic
      amendment applications against F. oxysporum f. sp. spinaciae is evaluable by this
      method. The co-cultivation method may be useful for predicting and diagnosing
      suppressiveness against soil-borne diseases.

PMID- 29459499
TI  - Long-Term Cultivation and Metagenomics Reveal Ecophysiology of Previously
      Uncultivated Thermophiles Involved in Biogeochemical Nitrogen Cycle.
AB  - Many thermophiles thriving in a natural high-temperature environment remain
      uncultivated, and their ecophysiological functions in the biogeochemical cycle
      remain unclear. In the present study, we performed long-term continuous
      cultivation at 65 degrees C and 70 degrees C using a microbial mat sample,
      collected from a subsurface geothermal stream, as the inoculum, and reconstructed
      the whole genome of the maintained populations using metagenomics. Some
      metagenome-assembled genomes (MAGs), affiliated into phylum-level bacterial and
      archaeal clades without cultivated representatives, contained genes involved in
      nitrogen metabolism including nitrification and denitrification. Our results show
      genetic components and their potential interactions for the biogeochemical
      nitrogen cycle in a subsurface geothermal environment.

PMID- 29459500
TI  - Choroid plexus carcinoma with neuronal and glial differentiation in a 7-week-old
      male Sprague-Dawley rat.
AB  - We describe a case of choroid plexus carcinoma arising in the cerebrum of a 7
      week-old male Sprague-Dawley rat. The tumor mass occupied the right lateral
      ventricle of the cerebrum. Histological analyses revealed that the epithelial
      tumor cells had proliferated in tubular, cribriform, papillary and solid growth
      patterns in the vicinity of the choroid plexus, with slight invasion into the
      cerebrum parenchyma. We divided the tumor cells into cuboidal, elongated and
      intermediate cells. Immunohistochemical studies showed that these tumor cells
      expressed relatively high levels of cytokeratin AE1/AE3, vimentin and glial
      fibrillary acidic proteins, and low levels of nestin, oligodendrocyte
      transcription factor and doublecortin proteins. The present case was diagnosed as
      a choroid plexus carcinoma with neuronal and glial differentiation.

PMID- 29459501
TI  - Effects of Rhizobium Species Living with the Dark Septate Endophytic Fungus
      Veronaeopsis simplex on Organic Substrate Utilization by the Host.
AB  - Bacteria harbored in/on the hyphae of the dark septate endophyte, Veronaeopsis
      simplex Y34, were identified as a single Rhizobium species by molecular analyses
      of bacterial 16S rRNA genes, and were successfully isolated from the endophyte.
      The Rhizobium-cured fungus was prepared thoroughly by an antibiotic treatment,
      thereby allowing an examination of their effects on organic substrate
      utilization. Assays with Biolog(r) FF microplates revealed that the respiration
      potential for 52.6% of the tested compounds were significantly different between
      Rhizobium-harboring and -cured fungal hosts, indicating that organic substrate
      utilization by V. simplex Y34 was significantly influenced by the presence of the
      associated Rhizobium sp. VsBac-Y9.

PMID- 29459502
TI  - Innovative, intra-articular, prosthetic technique for cranial cruciate ligament
      reconstruction in dogs: a cadaveric study.
AB  - The purpose of this study was to describe and assess the feasibility of a new
      intra-articular approach in the treatment of cranial cruciate ligament deficiency
      in dogs using an artificial ligament and a new bone-anchor system. Twelve canine
      cadavers weighting 26 to 45 kg were used in this ex-vivo study. Special tibial
      and femoral screws, two helicoils, and a high resistance artificial fiber compose
      the implant. Surgery was performed using the cranio-lateral approach to the
      stifle joint. Helicoil and tibial screw, connected to the fiber, were inserted in
      the center of the tibial insertion area of the cranial cruciate ligament. The
      fiber was passed over-the-top, tensioned, and fixed to the femoral screw,
      previously inserted with the helicoil in the distal part of the femur. Surgery
      was completed in all the cases. Occasional problems found during the insertion of
      the helicoils and screws were resolved with simple procedures. Post-operative
      clinical assessment showed negative cranial drawer test, negative cranial tibial
      thrust, and normal range of motion. Radiographic evaluation showed an appropriate
      positioning of both tibial and femoral implants in all the cases. The results of
      the first surgical appraisal of this new technique are encouraging, although
      further studies are necessary to demonstrate the in vivo efficacy of this
      procedure.

PMID- 29459503
TI  - First report of feline bocavirus associated with severe enteritis of cat in
      Northeast China, 2015.
AB  - Feline bocavirus (FBoV) is a newly identified bocavirus of cats in the family
      Parvoviridae. A novel FBoV HRB2015-LDF was first identified from the cat with
      severe enteritis in Northeast China, with an overall positive rate of 2.78%
      (1/36). Phylogenetic and homologous analysis of the complete genome showed that
      FBoV HRB2015-LDF was clustered into the FBoV branch and closely related to other
      FBoVs, with 68.7-97.5% identities. And the genes of VP1, NPA and NS1 shared 70.7
      97.6, 72.4-98.6 and 67.2-98.0% nucleotide identities with other FBoVs,
      respectively. The results suggested that the FBoVs could be divided into two
      distinct lineages, and the difference of nucleotide identities was >20-30%
      between the lineages.

PMID- 29459504
TI  - Isolation and molecular characterization of parainfluenza virus 5 in diarrhea
      affected piglets in China.
AB  - Recently, parainfluenza virus 5 (PIV5) infection has been increasingly reported
      in mammals. In this study, five PIV5 strains were isolated from diarrhea-affected
      piglets from four provinces or municipalities in China. An F-gene-based
      phylogenetic tree indicated that the five isolated strains were closely related
      to the PIV5 strain ZJQ-221 from a lesser panda in China, and the PIV5 strain 1168
      1 from a dog in South Korea. The new isolates differed genetically from other
      pig, calf, rhesus macaque kidney cells, human, and dog PIV5 reference strains.
      Our study reveals the presence of PIV5 in intestinal tissue samples collected
      from diarrhea-affected piglets, and provides novel information regarding the
      epidemiology and tissue tropism of PIV5.

PMID- 29459505
TI  - Acute hemorrhagic diarrhea syndrome associated with contaminated foreign bodies
      (used feminine hygiene products) in a Golden Retriever dog.
AB  - A one-year-old male Golden Retriever presented with acute onset of vomiting and
      hemorrhagic diarrhea since 2 days. The dog was depressed, showing abdominal pain,
      12% dehydration, tachycardia, and a bounding pulse. Diagnostic imaging showed
      severe dilatation and fluid retention of the entire gastrointestinal tract with
      decreased motility. A foreign body was found in the gastroduodenal region, but
      there was no obstruction or plication. The dog was tentatively diagnosed with
      acute hemorrhagic diarrhea syndrome and rapidly recovered after supportive
      treatment. However, on the morning of day 4, anorexia and vomiting recurred, and
      diagnostic imaging revealed intestinal plication with free peritoneal fluid, not
      found on the previous image. An emergency laparotomy revealed the foreign body to
      be two used feminine hygiene products. These contaminated products were suspected
      to induce acute hemorrhagic diarrhea syndrome, and led to subsequent complication
      in this large dog.

PMID- 29459506
TI  - Quantitative Analysis of the Accumulation of Marine-derived Tocopherol in the
      Tissue of Mice Fed with Salmon Roe Oil Using HPLC-fluorescence.
AB  - In this study, we measured the quantity of marine-derived tocopherol (MDT), a
      monounsaturated vitamin E (VE), stored in the body tissue of mice fed with a diet
      containing a VE-rich fraction extracted from salmon roe. We first prepared the
      calibration curves for the MDT concentration using an HPLC-fluorescence system.
      Ranging from 0.016 to 50 MUg/mL, the slope was expressed as first-order
      equations, with R2 values = 0.99. The mice were fed with an AIN-93 based diet
      containing MDT in doses of 21.4 mg/kg for 4 weeks, and the storage in the heart,
      lung, liver, stomach, small intestine, large intestine, kidney, pancreas, spleen,
      testis, skeletal muscle, visceral white adipose tissue (WAT), subcutaneous WAT
      and brain was quantified. MDT was widely distributed in tissues throughout the
      whole body, with higher accumulations observed in the adipose tissue, liver and
      kidney. These results demonstrate means to estimating the MDT concentration in
      natural products and in the bodies of animals and contribute to the understanding
      of the physiological functions of MDT in relation to human health.

PMID- 29459507
TI  - Synthesis of Fatty Acid Methyl Esters Using Mixed Enzyme in a Packed Bed Reactor.
AB  - Fatty acid methyl esters were synthesized from palm fatty acid distillate (PFAD)
      and methanol in a packed bed reactor via lipase-catalyzed esterification. The
      PFAD consisted of 91 wt% of free fatty acids, 2 wt% monoacylglycerides, 3 wt%
      diacylglycerides, and 4 wt% triacylglycerides. t-Butanol was employed as a
      reaction medium and a mixed enzyme consisting of Lipozyme TL IM from Thermomyces
      lanuginosus and Novozym 435 from Candida antarctica was employed as the
      biocatalyst. The effect of mixed enzyme was investigated and the optimum blending
      ratio (w/w) of Novozym 435 to Lipozyme TL IM was 5:95. Using the mixed enzyme,
      the optimum molar ratio (PFAD to methanol) and temperature were determined to be
      1:6 and 30 degrees C, respectively. Under the optimized conditions, the maximum
      yield of ca. 96% was achieved.

PMID- 29459508
TI  - Hepatic Regeneration and Reno-Protection by Fish oil, Nigella sativa Oil and
      Combined Fish Oil/Nigella sativa Volatiles in CCl4 Treated Rats.
AB  - The aim of the present research was to investigate the effect of fish oil, crude
      Nigella sative oil and combined fish oil/Nigella sative volatile oil as hepato
      regenerative and renal protective supplements. The oils were administered as
      emulsions to rat model with liver injury induced by CCl4. Plasma activities of
      transaminases (AST and ALT) were evaluated as liver function indicators, while
      plasma creatinine and urea and creatinine clearance were determined as markers of
      kidney function. Plasma malondialdehyde (MDA), nitrite (NO) and tumor necrosis
      factor-alpha (TNF-alpha) were estimated to assess the exposure to oxidative
      stress and subsequent inflammation. Liver fat was extracted and their fatty
      acids' methyl esters were determined using gas chromatography. Results showed
      that plasma activities of AST and ALT were significantly higher in CCl4 control
      group compared to control healthy group. Plasma levels of creatinine and urea
      increased significantly in CCl4 control, while creatinine clearance was reduced
      significantly in the same group. All rat treated groups given the three oil
      emulsions showed improvement in liver function pointing to the initiation of
      liver regeneration. The combination of fish oil/Nigella sative volatiles showed
      the most promising regenerative activity. Oxidative stress and inflammation which
      were increased significantly in CCl4 control group showed improvement on
      administration of the three different oil emulsions. Fatty acids methyl ester of
      liver fat revealed that rats treated with fish oil/Nigella sative volatile oil
      presented the highest content of unsaturated fatty acids (45.52% +/- 0.81) while
      fish oil showed the highest saturated fatty acids (53.28% +/- 1.68). Conclusion;
      Oral administration of oil emulsions of native fish oil, Nigella sative crude oil
      and combined fish oil/Nigella sative volatile oil reduced liver and kidney injury
      in rat model of CCl4 through exerting anti-inflammatory and antioxidant activity.
      Fish oil/Nigella sative volatile oil emulsion was the most promising hepato
      regenerative and reno-protective formula among the different groups.

PMID- 29459509
TI  - Study of Trans Fatty Acid Formation in Oil by Heating Using Model Compounds.
AB  - The intake of trans fatty acids (TFAs) in foods changes the ratio of low density
      lipoprotein (LDL) to high density lipoprotein (HDL) cholesterol in blood, which
      causes cardiovascular disease. TFAs are formed by trans isomerization of
      unsaturated fatty acids (UFAs). The most recognized formation mechanisms of TFAs
      are hydrogenation of liquid oil to form partially hydrogenated oil (PHO,) and
      biohydrogenation of UFAs to form TFA in ruminants. Heating oil also forms TFAs;
      however, the mechanism of formation, and the TFA isomers formed have not been
      well investigated. In this study, the trans isomerization mechanism of
      unsaturated fatty acid formation by heating was examined using the model
      compounds oleic acid, trioleate, linoleic acid, and trilinoleate for liquid plant
      oil. The formation of TFAs was found to be suppressed by the addition of an
      antioxidant and argon gas. Furthermore, the quantity of formed TFAs correlated
      with the quantity of formed polymer in trioleate heated with air and oxygen.
      These results suggest that radical reactions form TFAs from UFAs by heating.
      Furthermore, trans isomerization by heating oleic acid and linoleic acid did not
      change the original double bond positions. Therefore, the distribution of TFA
      isomers formed was very simple. In contrast, the mixtures of TFA isomers formed
      from PHO and ruminant UFAs are complicated because migration of double bonds
      occurs during hydrogenation and biohydrogenation. These findings suggest that
      trans isomerization by heating is executed by a completely different mechanism
      than in hydrogenation and biohydrogenation.

PMID- 29459510
TI  - Effects of Fatty Acid Addition to Oil-in-water Emulsions Stabilized with Sucrose
      Fatty Acid Ester.
AB  - Adding fatty acids to an oil-in-water (O/W) emulsion changes the stability of the
      emulsion. In this study, we prepared a series of O/W emulsions consisting of oil
      (triolein/fatty acid mixture), water and a range of surfactants (sucrose fatty
      acid esters) with varying hydrophilic-lipophilic balance (HLB) in order to
      determine the effects of alkyl chain length and the degree of unsaturation of the
      fatty acid molecules on the stability of the emulsions. As a result, sucrose
      fatty acid esters with HLB = 5-7 were suitable for obtaining O/W emulsions. In
      addition, the creaming phenomenon was inhibited for 30 days or more when fatty
      acids having a linear saturated alkyl chain with 14 or more carbon atoms were
      added. These findings are useful for designing stable O/W emulsions for food and
      cosmetic products.

PMID- 29459511
TI  - Optimization of Supercritical Carbon Dioxide Extraction of Eucommia ulmoides Seed
      Oil and Quality Evaluation of the Oil.
AB  - Supercritical carbon dioxide extraction (SC-CO2) technology was used to extract
      oil from Eucommia ulmoides seed. The optimum conditions and significant
      parameters in SC-CO2 were obtained using response surface methodology (RSM). The
      qualities of the extracted oil were evaluated by physicochemical properties,
      fatty acid composition, vitamin E composition. It was found that the optimum
      extraction parameters were at pressure of 37 MPa, temperature of 40 degrees C,
      extraction time of 125 min and CO2 flow rate of 2.6 SL/min. Pressure, temperature
      and time were identified as significant parameter effecting on extraction yield.
      The importance of evaluated parameters decreased in the order of pressure >
      extraction time > temperature > CO2 flow rate. GC analysis indicated that E.
      ulmoides seed oil contained about 61% of linolenic acid and its fatty acid
      composition was similar with that of flaxseed oil and perilla oil. The content
      and composition of vitamin E was determined using HPLC. The E. ulmoides seed oil
      was rich in vitamin E (190.72 mg/100 g), the predominant vitamin E isomers were
      gamma- tocopherol and delta- tocopherol, which accounted for 70.87% and 24.81% of
      the total vitamin E, respectively. The high yield and good physicochemical
      properties of extracted oil support the notion that SC-CO2 technology is an
      effective technique for extracting oil from E. ulmoides seed.

PMID- 29459512
TI  - Effects of Ethanol and Cholesterol on Thermotropic Phase Behavior of Ion-Pair
      Amphiphile Bilayers.
AB  - Ion-pair amphiphiles (IPAs, also known as catanionic surfactants) are lipid-like
      double-chained molecules potentially used for fabricating liposome-like vesicular
      drug and gene carriers. Frequently ethanol and cholesterol are added to modulate
      the properties of their bilayer membranes. Effects of ethanol and cholesterol on
      the fundamental properties of IPA bilayers such as thermotropic phase behavior,
      however, is not known. In this work, the bilayer phase transition behavior of two
      IPAs (decyltrimethylammonium-tetradecyl sulfate, DeTMA-TS, and
      dodecyltrimethylammonium-dodecyl sulfate, DTMA-DS) in tris buffer with various
      amounts of ethanol was studied by using differential scanning calorimetry (DSC).
      Effect of cholesterol (CHOL) addition on bilayer phase transition of IPAs with 20
      vol% ethanol was thereafter systematically investigated. The experimental results
      showed that the main phase transition temperature (Tm) was monotonously decreased
      with the increase of ethanol concentration up to 30 vol%. The degree of Tm
      depression by ethanol is essentially the same for the two IPAs regardless of
      different symmetry in the hydrocarbon chains. Further addition of CHOL, however,
      caused a slight decrease in Tm on the one hand and a significant decrease in the
      enthalpy of phase transition on the other hand. When the added CHOL exceeded a
      specific amount, the phase transition disappeared. More hasty disappearance of
      phase transition was found for IPA with asymmetric structure than the symmetric
      one. Possible mechanisms of ethanol effect based on binding in the headgroup
      region of the bilayers and CHOL effect based on opposite (condensing and
      disordering) interactions with IPA molecules in bilayers, respectively, were
      proposed.

PMID- 29459513
TI  - Hydrogel-Templated Solid Base Catalysts for Transesterification of Soybean Oil.
AB  - A new method for utilization of hydrogel is proposed here for the preparation of
      solid base catalysts for the transesterification of vegetable oil. When a
      solution of KF is mixed with a solution of Ca(NO3)2, CaF2 is obtained and
      inactive as a catalyst in the transesterification of vegetable oils. The
      catalysts were synthesized by the sequential incorporation of KF and/or Ca(NO3)2
      solutions into the hydrogel upon microwave irradiation and then the as-obtained
      hydrogel was calcined at 800 degrees C for 5 hours to eliminate the template and
      yield catalysts for the biodiesel productions. The prepared catalysts obtained by
      the different ways in the incorporation of ions into the hydrogel showed
      different physical properties and catalytic activities in the transesterification
      of soybean oil. All catalysts, except the low concentration of Ca(NO3)2,
      exhibiting the high activity yielding more than 90% FAME after 1 hour at 65
      degrees C, using oil to methanol molar ratio of 1:15 and 10 wt% of catalyst
      amounts.

PMID- 29459514
TI  - Activation of Macrophages in vitro by Phospholipids from Brain of Katsuwonus
      pelamis (Skipjack Tuna).
AB  - The biological activities of phospholipids (PLs) have attracted people's
      attention, especially marine phospholipids with omega-3 polyunsaturated fatty
      acids DHA and EPA. In this study, we investigated the immunity activation of
      macrophages in vitro by phospholipids from skipjack brain. The phospholipids were
      extracted with hexane and ethanol ultrasonication instead of the traditional
      method of methanol and chloroform. The content of phospholipids from Skipjack
      brain was 19.59 g/kg by the method (the ratio of hexane and ethanol 2:1, 40 min,
      35 degrees C, 1:9 of the ratio of material to solvent, ultrasonic power 300W,
      ultrasonic extraction 2 times). The RAW264.7 macrophages were stimulated by the
      phospholipids from the Skipjack, by which the volume, viability and phagocytosis
      of macrophages were increased. The concentration of NO and the activity of SOD of
      the cells were also enhanced. The gene expressions of IL-1beta, IL-6, iNOS and
      TNF-alpha mRNA assayed by RT-PCR were up-regulated. Phospholipids from brain of
      Skipjack Tuna could activate macrophages immunity which displayed to induce pro
      inflammatroy cytokines mRNA expression.

PMID- 29459516
TI  - Development of a Novel Spontaneous Emulsification Method for Peptide Delivery
      Using Porous Silica Particles.
AB  - A new emulsification technique using porous silica particles was studied as a
      facile and instantaneous formation method for thermodynamically unstable
      emulsions. In this study, oil encapsulated in silica particles was released
      instantly upon the addition of a phosphate buffer, forming an oil-in-water (O/W)
      emulsion. Emulsion formation was inhibited or promoted using lipophilic or
      hydrophilic surfactant additives, respectively. We concluded that this phenomenon
      is affected by the wettability of the soybean oil on the silica surface, which is
      controlled by the surfactant. We prepared submicron size emulsions in a simple
      method involving the addition of the silica particles to an aqueous solution.
      This spontaneous emulsification technique could be applied to the formation of
      solid-in-oil-in-water (S/O/W) emulsions for oral delivery of hydrophilic peptide
      medicine.

PMID- 29459515
TI  - Yuzu (Citrus junos Tanaka) Peel Attenuates Dextran Sulfate Sodium-induced Murine
      Experimental Colitis.
AB  - Ulcerative colitis is a well-known inflammatory bowel disease. Although there are
      drugs that are effective against this disease, the prevention and attenuation of
      ulcerative colitis by food rich in functional ingredients without side effects is
      desired because some drugs have side effects. In this study, we investigated the
      effects of yuzu (Citrus junos Tanaka), a citrus fruit native to northeast Asia,
      on a mouse dextran sulfate sodium (DSS)-induced colitis model. Mice given
      drinking water containing DSS showed significant weight loss, colon shortening,
      diarrhea, and visible fecal blood. In contrast, mice fed a diet containing 5%
      yuzu peel for 14 d before receiving DSS showed significant attenuation of these
      phenotypes. To clarify the mechanism underlying the attenuation, we investigated
      the anti-inflammatory and antioxidant effects of yuzu peel. We found that yuzu
      peel extract suppressed tumor necrosis factor-alpha (TNF-alpha) production in
      lipopolysaccharide (LPS)-stimulated mice and murine macrophage cell line through
      suppression of nuclear factor-kappaB (NF-kappaB) activation. In addition, we
      confirmed that yuzu peel extract had a moderate antioxidant effect. These results
      suggest that yuzu peel attenuates the pathologies of DSS-induced colitis by
      coordinately suppressing inflammation and oxidative stress against lipids in
      vivo.

PMID- 29459519
TI  - [FOOD ALLERGY AND ANAPHYLAXIS].

PMID- 29459517
TI  - Reduced Lung Function and Cerebral Small Vessel Disease in Japanese Men: the
      Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).
AB  - AIM: We aimed to investigate the association between reduced lung function and
      cerebral small vessel diseases via cranial magnetic resonance imaging (MRI) in
      the cross-sectional study of the general Japanese population. METHODS: We
      recruited participants aged >=40 years from the general population of a single
      city in Japan. We clarified the comorbidities and treatments, smoking habits,
      second-hand smoke exposure, current alcohol consumption, education level,
      exercise habits, and occupation. The pulmonary function test was performed to
      assess the forced expiratory volume in 1 second (FEV1) % predicted and forced
      vital capacity (FVC) % predicted values. Cranial MRI was performed to evaluate
      the white matter lesions (WMLs) and lacunar infarcts. We examined the association
      of the WMLs and lacunar infarcts with a 1-standard deviation (SD) lower in the
      FEV1 % predicted and FVC % predicted, on the basis of the smoking status.
      RESULTS: A total of 473 men were examined. The association of WMLs and lacunar
      infarcts with the spirometry-based indices were significant only in never
      smokers. The association between lung function impairment and cerebral small
      vessel disease did not change after further adjusting for second-hand smoke
      exposure. CONCLUSION: In a community-based sample of Japanese men, we found an
      association between reduced lung function and WMLs and lacunar infarcts in never
      smokers.

PMID- 29459518
TI  - Noninvasive Assessment of Stenotic Severity and Plaque Characteristics by
      Coronary CT Angiography in Patients Scheduled for Carotid Artery
      Revascularization.
AB  - AIMS: Coronary artery atherosclerosis in patients needing carotid
      revascularization has not been fully clarified. The aim of this study was to
      evaluate the stenotic severity and plaque characteristics of coronary arteries by
      coronary computed tomography angiography (CTA) in patients scheduled for carotid
      artery stenting (CAS) or carotid endarterectomy (CEA). METHODS: We performed
      coronary CTA after carotid ultrasound (US) in 164 patients (81.7% male, aged
      68.1+/- 12.2 years) from 2014 to 2016. Of all, 70 were scheduled for CAS or CEA
      (CAS/CEA group) and 94 were not (non-CAS/CEA group). Carotid US and coronary CTA
      were compared for the evaluation of stenotic severity and plaque characteristics
      of each vessel between CAS/CEA and non-CAS/CEA groups. RESULTS: Between the two
      groups, there were significant differences in the presence of significant
      stenosis (SS: >=70% stenosis of coronary artery) (55.7% vs. 39.4%, P=0.038),
      triple-vessel disease (TVD)/left main trunk (LMT) (SS in each of three epicardial
      vessels and/or LMT) (24.3% vs. 7.5%, P= 0.0025), and high-risk plaque (HRP:
      positive remodeling and/or low attenuation) (55.7% vs. 24.5%, P<0.0001). CAS/CEA
      was independently associated with TVD/LMT (OR=2.30, 95%CI: 1.14-8.59, P=0.026)
      and HRP (OR=3.17, 95%CI: 1.57-6.54, P=0.0012) in multivariable logistic
      regression analysis. Similarly, vulnerable plaque (78.6% vs. 2.1%, P<0.0001) as
      well as severe stenosis of carotid artery (98.6% vs. 0%, P<0.0001) was seen more
      often in CAS/CEA than in non-CAS/CEA group. CONCLUSIONS: The prevalence of
      TVD/LMT and HRP determined by coronary CTA is higher in patients needing CAS/CEA
      than in those without. Management of systemic atherosclerosis is required in the
      perioperative period of CAS/CEA.

PMID- 29459520
TI  - [ANAPHYLAXIS GUIDELINE].

PMID- 29459521
TI  - [THE IMMUNE RESPONSE TO PREVOTELLA BACTERIA IN AUTOIMMUNE DISEASES].

PMID- 29459522
TI  - [EOSINOPHILS AND ANTI-INFLAMMATORY LIPID MEDIATORS].

PMID- 29459523
TI  - [THE ROLE OF MAST CELL-DERIVED LIPID MEDIATORS IN ANAPHYLAXIS].

PMID- 29459524
TI  - [THE CLINICAL CHARACTERISTICS OF PEANUT ALLERGY AND THE DIAGNOSTIC ACCURACY OF
      THE SPECIFIC IgE TO Ara h 2].
AB  - BACKGROUND: This study aimed to evaluate the clinical accuracy of specific IgE
      (sIgE) to Ara h 2 in the diagnosis of peanut allergy (PA). We also investigated
      the prevalence of complications with other nut allergies in PA patients. METHODS:
      The Ara h 2-sIgE titer was examined in patients with positive results for sIgE to
      peanut from April 2014 to March 2015. The presence or absence of PA was diagnosed
      based on an oral food challenge or a convincing clinical history. The
      characteristics of 217 patients (including 90 PA patients) were retrospectively
      evaluated. RESULTS: At >=0.35UA/mL, Ara h 2 showed 85.6% sensitivity in the
      diagnosis of PA. At the clinically-designated positive cut-off value
      (>=4.0UA/mL), the positive predictive value was 93.1% and the specificity was
      96.9%. However, the Ara h 2-sIgE levels were not correlated with the threshold
      dose or the severity of the symptoms that were provoked in the peanut challenge
      (n=42). Nine (10%) of the PA patients also had allergies to other tree nuts.
      CONCLUSION: The re-evaluation of the clinically-designated positive Ara h 2-sIgE
      cut-off value revealed that the cut-off value was appropriate. The differential
      diagnosis of tree nut allergies was suggested to be important in PA patients.

PMID- 29459525
TI  - [THE CAUSES OF ACUTE COUGH: A SINGLE-CENTER STUDY IN JAPAN].
AB  - BACKGROUND: Cough is the most frequent presenting complaint in clinics, and is
      classified into the following three groups: acute, subacute and chronic. The
      major causes of acute cough are infectious diseases, however, few observations on
      acute cough have been reported. METHODS: We retrospectively assessed the causes
      of acute cough among patients who had visited the respiratory clinic of our
      hospital because of acute cough from September 2014 to August 2015. RESULTS: Of
      374 patients (195 females, mean age 60.3 years) who visited the clinic
      complaining of cough, 129 patients (63 females, mean age 61.5 years) suffered
      from acute cough. All acute cases were stratified into two groups based on the
      presence (n=43) or absence (n=86) of abnormal findings on the chest X-ray. The
      main causes of acute cough with abnormal findings were pneumonia (46.5%),
      interstitial pneumonia (18.6%) and lung cancer (16.3%). The main causes of acute
      cough without abnormal findings were respiratory tract infection (39.5%), post
      infectious cough (18.6%) and bronchial asthma (17.4%). Acute cough was the
      primary complaint in 29.5% and 19.6% of all patients diagnosed with bronchial
      asthma and cough variant asthma, respectively. CONCLUSION: Non-infectious
      diseases including asthma as well as infectious diseases could be the causes in
      acute cough without abnormal findings on the chest X-ray.

PMID- 29459526
TI  - [THE COURSE OF ASTHMA SYMPTOMS IN JAPANESE CHILDREN; THE FIRST REPORT FROM A
      MULTICENTER PROSPECTIVE COHORT STUDY].
AB  - BACKGROUND: The use of asthma control guidelines and anti-inflammatory drugs have
      significantly decreased the number of severe asthma cases including death from
      asthma. However, there are few prospective cohort studies among pediatric asthma
      patients in Japan describing the course of asthma symptoms with the treatment
      taken into consideration. METHOD: We recruited a total of 851 children diagnosed
      with asthma through 90 hospitals and clinics in 2004 to 2006. Questionnaires were
      posted annually to collect data on their asthma symptoms, treatment and
      environmental exposures. We analyzed the disease course in the first 5 years
      among the children who were registered at age 4 or younger. RESULTS: The disease
      course of a total of 641 children, aged 2.8+/-1.1 (mean+/-SD) at registration
      were analyzed. The proportion of children who had intermittent symptoms increased
      from 37.6% at registration to 86.5% at 5 years, and the proportion of children
      with intermittent severity increased from 7.0% to 38.9%, showing a significant
      decrease in the overall severity. The proportion of children using beta2
      stimulants decreased from 87.8% at registration to 53.5% at 5 years, while the
      use of inhaled cortico-steroids were 41.6% at registration and 38.1% at 5 years.
      CONCLUSION: Most of the children with pre-school onset asthma had their symptoms
      controlled, and had decreased severity over 5 years.

PMID- 29459527
TI  - [A CASE OF SUMMER-TYPE HYPERSENSITIVITY PNEUMONITIS ACCOMPANIED BY THE SYNDROME
      OF INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE].
AB  - A 47-year old man presented to our hospital with a 6-month history of malaise,
      cough and dyspnea on exertion. Laboratory testing revealed the severe
      hyponatremia. A chest X-ray showed bilateral diffuse micronodules. Anti
      Trichosporon asahii antibody and environmental provocation test were positive.
      Bronchoalveolar lavage fluid showed lymphocytosis and low CD4/8 ratio. The
      specimens obtained by transbronchial lung biopsy revealed alveolitis. Based on
      these findings, the patient was diagnosed as having summer-type hypersensitivity
      pneumonitis (SHP). The patient was treated with antigen avoidance and oral
      corticosteroid. The hyponatremia caused by syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH) was treated with normal saline and water
      restriction. Serum sodium level was improved with treatment of SHP, which
      suggested the relevance between SHP and SIADH.

PMID- 29459528
TI  - [A VALIDATION STUDY OF THE IMPROVED PRODUCT FOR MEASURING JAPANESE CYPRESS POLLEN
      SPECIFIC IgE (THERMO SCIENTIFICTM ImmunoCAPTM ImmunoCAP JAPANESE CYPRESS POLLEN
      SPECIFIC IgE)].
AB  - BACKGROUND: Japanese cypress pollen is a major causative allergen of seasonal
      allergic rhinitis in Japan. Although ImmunoCAP-specific immunoglobulin E (IgE)
      reagent Japanese cypress pollen has been widely used as a diagnostic aid, its
      sensitivity requires enhancement. This study evaluated an improved version of
      this reagent. METHODS: Serum samples from 61 subjects who underwent Japanese
      cypress pollen exposure testing in an environmental challenge chamber in Chiba
      University were assessed using the conventional ImmunoCAPspecific IgE Japanese
      cypress pollen product and the improved product. In addition, specific IgE for
      Cha o 1 and Cha o 2, the primary allergen components of Japanese cypress pollen,
      was evaluated and their reactivity to specific IgE was compared between the
      conventional and improved products. RESULTS: The antibody titer of the improved
      product was approximately 1.8-fold that of the conventional product. In addition,
      higher correlations with Cha o 1 and Cha o 2 were observed for the improved
      product than for the conventional product. The clinical sensitivity (>=class 2)
      in 56 exposure test-positive subjects was better for the improved product (80.4%)
      than for the conventional product (71.4%). CONCLUSIONS: An improvement of the
      ImmunoCAP-specific IgE reagent Japanese cypress pollen resulted in enhanced
      Japanese cypress pollen-specific IgE sensitivity. The primary reason for this
      appeared to be an improved Cha o 1- and Cha o 2-specific IgE detectability.

PMID- 29459529
TI  - [galactose-alpha-1,3-galactose (alpha-gal)].

PMID- 29459530
TI  - ?

PMID- 29459531
TI  - [Siglec-F/-8].

PMID- 29459532
TI  - [URTICARIA AND ANAPHYLAXIS].

PMID- 29459534
TI  - Localized Doxorubicin-Induced Cardiomyopathy Complicated With Shower Emboli
      Originating From Apical Intramural Thrombi.

PMID- 29459533
TI  - Macromolecular crowded conditions strengthen contacts between mouse oocytes and
      companion granulosa cells during in vitro growth.
AB  - Macromolecular crowded culture medium formed by addition of polyvinylpyrrolidone
      (PVP; molecular weight = 360 000), positively influences the viability, growth,
      and development of bovine oocytes. Owing to its apparently various effects,
      uncovering the specific mechanisms of crowding responsible for these outcomes is
      important. The present study was conducted to determine the effects of crowding
      on oocytes with a particular focus on the intimacy of contacts between oocyte and
      cumulus/granulosa cells. Growing mouse oocyte-granulosa cell complexes were
      cultured for 10 days in a modified alpha-minimum essential medium, supplemented
      with PVP at a concentration of 0%, 1%, 2%, or 3% (w/v). Although the complexes
      developed in all groups, 2% and 3% PVP medium induced a substantial morphological
      modification, and a larger proportion of oocytes associated with cumulus cells
      survived in 3% PVP medium than in the 0% or 1% PVP medium. No significant
      difference was found in the frequencies of polar body extrusion (78-88%) and
      blastocyst formation (approximately 40%) after in vitro fertilization among the
      experimental groups. Confocal laser scanning microscopy indicated a higher number
      of transzonal processes reaching the oocyte from cumulus cells in 2% PVP medium
      than in 0% PVP medium. Transmission electron microscopy depicted close adhesion
      of the oocyte with cumulus cells in 2% PVP medium -bearing a resemblance to their
      in vivo counterparts- and loose adhesion in 0% PVP medium. In conclusion, we
      found that a mechanism for the action of crowded conditions involves the
      strengthening of contacts and communication between oocytes and companion
      cumulus/granulosa cells.

PMID- 29459535
TI  - Vascular Digit Injury in a College Baseball Player.

PMID- 29459536
TI  - Mesoangioblasts - A Newcomer in Cell-Based Treatment Strategy for Cardiovascular
      Disease?

PMID- 29459537
TI  - [The Effect of Scan Parameters on the Synthetic MRI].
AB  - Synthetic MRI can provide proton density (PD), T1 value, T2 value for each pixel
      by only one data acquisition and can create various contrast-weighted images. The
      aim of this study is to evaluate the effect on the calculation of the T1.T2 value
      when changing the scan parameters for synthetic MRI. In the phantom study, when
      changing 1st TE/2nd TE/TR/TSE factor, the effect on the T1.T2 value calculated by
      synthetic MRI was examined. In the volunteer study, the brain was imaged and
      compared with known T1.T2 value. In phantom study, the effect on the T2 value by
      the 1st TE/2nd TE/TSE factor was shown. In volunteer study, there was no problem
      in the calculated value of brain parenchyma. However, the T2 value of
      cerebrospinal fluid had the error of known value. The results show that it is
      necessary to set appropriate scan parameters on synthetic MRI.

PMID- 29459538
TI  - [Development of a Striatal and Skull Phantom for Quantitative 123I-FP-CIT SPECT].
AB  - BACKGROUND: 123Iodine-labelled N-(3-fluoropropyl) -2beta-carbomethoxy-3beta-(4
      iodophenyl) nortropane (123I-FP-CIT) single photon emission computerized
      tomography (SPECT) images are used for differential diagnosis such as Parkinson's
      disease (PD). Specific binding ratio (SBR) is affected by scattering and
      attenuation in SPECT imaging, because gender and age lead to changes in skull
      density. It is necessary to clarify and correct the influence of the phantom
      simulating the the skull. PURPOSE: The purpose of this study was to develop
      phantoms that can evaluate scattering and attenuation correction. METHODS: Skull
      phantoms were prepared based on the measuring the results of the average computed
      tomography (CT) value, average skull thickness of 12 males and 16 females. 123I
      FP-CIT SPECT imaging of striatal phantom was performed with these skull phantoms,
      which reproduced normal and PD. SPECT images, were reconstructed with scattering
      and attenuation correction. SBR with partial volume effect corrected (SBRact) and
      conventional SBR (SBRBolt) were measured and compared. RESULTS: The striatum and
      the skull phantoms along with 123I-FP-CIT were able to reproduce the normal
      accumulation and disease state of PD and further those reproduced the influence
      of skull density on SPECT imaging. The error rate with the true SBR, SBRact was
      much smaller than SBRBolt. CONCLUSION: The effect on SBR could be corrected by
      scattering and attenuation correction even if the skull density changes with 123I
      FP-CIT on SPECT imaging. The combination of triple energy window method and CT
      attenuation correction method would be the best correction method for SBRact.

PMID- 29459539
TI  - [Optimization of Scan Parameters for Patient without Breath Hold in Chest by
      Computed Tomography].
AB  - This study aims to establish optimal scan parameters by high temporal resolution
      computed tomography (CT) scan for emergency patients who cannot hold their
      breath. First, we investigated scan parameters that can reduce the effect of
      motion by evaluating motion artifacts from the moving phantom scan and the
      temporal sensitivity profile (TPS) measurement. Second, we confirmed the standard
      deviation (SD) of the CT values as well as the operating time and exposure dose.
      As the results, plan C [rotation time: 0.275 s, detector rows: 80, pitch factor
      (PF): 1.100] and plan E (rotation time: 0.275 s, detector rows: 100, PF: 0.880)
      demonstrated high temporal resolution. The difference between the two is PF. The
      noise of plan C increased because PF is higher than plan E. This is also evident
      from the results of SD measurement. Our study demonstrates that the optimal
      parameters for patients who cannot hold their breath in the emergency care are
      plan C and plan E. In conclusion, we clarified necessary optimal scan parameters
      to provide clinical image that has more diagnostic information by reducing the
      effect of breath motion for emergency patients.

PMID- 29459540
TI  - [Coronary Computed Tomography Angiography for Patients with Atrial Fibrillation:
      Feasibility of Prospective Electrocardiography-gated Diastolic Acquisition with a
      Manual Exposure-termination Technique].
AB  - Coronary computed tomography angiography (CCTA) was performed in 283 patients
      with atrial fibrillation (Af) using a prospective electocardiogeaphic gated
      scanning with a manual exposure-termination technique. When preparatory 5-beat
      scanning contained at least one RR interval longer than 800 ms, 5-beat diastolic
      scanning (R+800 ms protocol) was selected. When no RR interval longer than 800 ms
      was observed, 2-beat scanning starting at end-systolic phase (R+210 ms to R
      protocol) was chosen. In R+800 ms protocol, we manually terminated scanning when
      motion free real-time reconstruction image was confirmed. R+800 ms protocol was
      applied in 95% of the cases and required an average of 2 cardiac cycles,
      providing motion-free images in 91% of the patients. The mean exposure dose was
      less than that with R+210 ms to R protocol. Using the protocols above, 90% of the
      all patients with Af provided motion free images and 99% of them were evaluable.

PMID- 29459541
TI  - [Measurement Accuracy of Fat and Iron Deposits in the Liver Using 1H-MRS
      (HISTO)].
AB  - 1H-MRS, which is a method of measuring fat and iron deposits in the liver, has a
      single voxel spectroscopy imaging method called high-speed T2-corrected multiecho
      (HISTO) based on the STEAM method. If HISTO measurement accuracy is high, it will
      be one of the biomarkers, so the measurement accuracy was examined. We imaged a
      self-made phantom simulating a known amount of fat and iron deposition in the
      liver. A regression analysis of HISTO-measured values for hepatic fat phantom was
      performed. In addition, regression analysis was performed on the hepatic iron
      phantom for the R2 values obtained from the T2 values measurement and the
      actually measured value of the HISTO. From the regression analysis, the
      correlation coefficients were 0.999, 0.992 and 0.977, respectively. The
      measurement accuracy of HISTO is high, and the reliability of the obtained fat
      and iron deposit value is high.

PMID- 29459542
TI  - [Development of Audio Indicator System for Respiratory Dynamic CT Imaging].
AB  - We created the device, which can conduct a radiological technologist's voice to a
      subject during CT scanning. For 149 lung cancer, dynamic respiratory CT were
      performed. 92 cases were performed using this device, the others were without
      this device. The respiratory cycle and respiratory amplitude were analyzed from
      the lung density. A stable respirating cycle was obtained by using the audio
      indicator system. The audio indicator system is useful for respiratory dynamic
      CT.

PMID- 29459543
TI  - [Wrapping of X-ray Cassette by a Plastic Bag in Portable Radiography: For
      Infection Prevention and Alleviation of Patient's Discomfort].
AB  - Portable radiography is available for the patient who is postoperative, severe
      condition and old. As they have weak immunity, it is important to prevent from
      hospital infection. Wrapping of 14*14 inch or 14*17 inch X-ray cassette by a
      plastic (polyethylene) bag a little bit bigger than the cassette was proposed for
      infection prevention in portable radiography. How to wrap the cassette easily was
      devised using the sheath of a polyester bag cutting at the bottom. In radiography
      with the grid, the plastic bag fastens the X-ray grid to the cassette
      substantially without any other means. In addition, the wrapped cassette, or the
      cassette with grid covered by the foamed plastic sheet alleviates patient's
      discomfort.

PMID- 29459544
TI  - [Comparison of Organ Dose Calculation Using Monte Carlo Simulation and In-phantom
      Dosimetry in CT Examination].
AB  - Direct measurement of each patient organ dose from computed tomography (CT) is
      not possible. Most methods to estimate patient organ dose is using Monte Carlo
      simulation with dedicated software. However, the method and the relative
      differences between organ dose simulation and measurement is unclear. The purpose
      of this study was to compare organ doses evaluated by Monte Carlo simulation with
      doses evaluated by in-phantom dosimetry. The simulation software Radimetrics
      (Bayer) was used for the calculation of organ dose. Measurement was performed
      with radio-photoluminescence glass dosimeter (RPLD) set at various organ
      positions within RANDO phantom. To evaluate difference of CT scanner, two
      different CT scanners were used in this study. Angular dependence of RPLD and
      measurement of effective energy were performed for each scanner. The comparison
      of simulation and measurement was evaluated by relative differences. In the
      results, angular dependence of RPLD at two scanners was 31.6+/-0.45 mGy for
      SOMATOM Definition Flash and 29.2+/-0.18 mGy for LightSpeed VCT. The organ dose
      was 42.2 mGy (range, 29.9-52.7 mGy) by measurements and 37.7 mGy (range, 27.9
      48.1 mGy) by simulations. The relative differences of organ dose between
      measurement and simulation were 13%, excluding of breast's 42%. We found that
      organ dose by simulation was lower than by measurement. In conclusion, the
      results of relative differences will be useful for evaluating organ doses for
      individual patients by simulation software Radimetrics.

PMID- 29459545
TI  - [Symposium 2: Integration of Medical Engineering and Radiological Technology:
      Expected New Technology].

PMID- 29459546
TI  - [Light and Shadow by Standardization of Gastrointestinal Examination
      (Radiological Technology)].

PMID- 29459547
TI  - [8. DRL for Nuclear Medicine].

PMID- 29459548
TI  - [4. Preparation of Heart Disease Models and Evaluation of Pathology Using
      Ultrasound Imaging].

PMID- 29459549
TI  - [8. How We Can Treat the Patients with Prostate Cancer-Surgical Option and Change
      over Time].

PMID- 29459550
TI  - [2. The Clinical Role of CT, MRI and FDG PET-CT for Gynecological Disorders].

PMID- 29459551
TI  - [Participation/Dispatch Reports on the 45th Autumn Scientific Congress].

PMID- 29459552
TI  - [Report of JIRA 50th Anniversary Study Meeting for Medical Imaging Industry].

PMID- 29459553
TI  - [The Review].

PMID- 29459555
TI  - Metabolic and immunological assessment of small-for-gestational-age children
      during one-year treatment with growth hormone: the clinical impact of
      apolipoproteins.
AB  - Children born small for gestational age (SGA) are at a higher risk for metabolic
      disorders later in life. In this study, we aimed to characterize young SGA
      children without catch-up growth and evaluate the effects of GH treatment on
      endocrinological, metabolic, and immunological parameters. Study design is a one
      year single hospital-based study included prospective observation of SGA patients
      during 12 months of GH treatment. Clinical and laboratory profiles of SGA
      children at baseline were compared with controls born appropriate size for age.
      Twenty-six SGA children (median age, 3.4 years) and 26 control children (median
      age, 3.8 years) were enrolled. Anthropometric, hematologic, biochemical,
      immunological, and endocrinological parameters were assessed at baseline and 1,
      3, 6, 9, and 12 months after the start of GH treatment. As a result, median
      height SD score (SDS) of SGA children increased by +0.42 with 12-month GH
      treatment. Body mass index SDS was lower in SGA children than in controls. Serum
      apolipoprotein A1 increased, whereas apolipoprotein B decreased during GH
      treatment. Serum leptin and resistin levels, which were lower in SGA children
      than in controls at baseline, did not change remarkably with GH treatment.
      Monocyte counts, which were lower in SGA patients at baseline, increased after GH
      treatment. Neutrophil counts significantly increased after GH treatment. Natural
      killer cell ratios, which were higher in SGA patients, decreased after GH
      treatment. In conclusion, there was no evidence suggesting metabolic
      abnormalities in SGA children. Serum apolipoprotein changes might predict the
      beneficial role of GH treatment in lowering cardiometabolic risk.

PMID- 29459554
TI  - Effect of sodium glucose cotransporter 2 inhibitors on obstructive sleep apnea in
      patients with type 2 diabetes.
AB  - Obstructive sleep apnea syndrome (OSAS) is often associated with metabolic
      disorders such as obesity and type 2 diabetes and may contribute to
      cardiovascular events. A novel class of antidiabetic drugs, the sodium glucose
      cotransporter 2 inhibitors (SGLT2i) reduce body weight (BW), although there is
      limited data on their impact on OSAS. We therefore evaluated the effect of SGLT2i
      on OSAS in patients with type 2 diabetes. The presented study was a retrospective
      design in 18 patients with type 2 diabetes with OSAS (4 males, age range 39-81
      yr) administrated a SGLT2i. HbA1c, BW, body mass index (BMI), blood pressure (BP)
      and apnea hypopnea index (AHI) were evaluated before and after SGLT2i
      administration. The relationships between the reduction in AHI and the other
      variables were examined using Pearson correlation analysis. We have got result
      that SGLT2i reduced AHI from 31.9 +/- 18.0 to 18.8 +/- 11.5 events per hr (p =
      0.003). HbA1c, BW and BMI decreased significantly, whereas BP did not. The
      Pearson correlation analysis showed a significant relationship between the
      reduction in AHI and pre-administration of AHI. In conclusion, SGLT2i reduced not
      only HbA1c, BW and BMI but also AHI significantly and therefore has potential as
      an effective treatment of OSAS.

PMID- 29459557
TI  - [Movement of duodenal endoscopical finding].

PMID- 29459556
TI  - Concurrent variant type 3 autoimmune polyglandular syndrome and pulmonary
      arterial hypertension in a Japanese woman.
AB  - We describe a very rare case of concurrent variant type 3 autoimmune
      polyglandular syndrome (APS) and pulmonary arterial hypertension (PAH). A
      previously healthy 65-year-old Japanese woman was referred to our university
      hospital with a 2-month history of general fatigue and hyperglycemia. Laboratory
      tests revealed severe hyperglycemia (plasma glucose 543 mg/dL and HbA1c 10.7%)
      with ketonuria (3+). Glutamic acid decarboxylase (GAD) and IA-2 antibodies were
      positive, and the serum C peptide level was markedly decreased to 0.2 ng/mL.
      Accordingly, type 1 diabetes was diagnosed. Hashimoto's thyroiditis was also
      diagnosed because she had a diffuse goiter and a mild hypothyroidism (TSH 8.20
      MUU/mL, and FT4 0.80 ng/mL) with positive autoantibodies for thyroid peroxidase
      and thyroglobulin. There was neither adrenal insufficiency nor hypocalcemia. In
      addition, chest X ray showed a suspicious PAH by a dilation of both pulmonary
      arteries, especially right descending artery, and right heart catheterization
      confirmed the presence of PAH. HLA Class II genotyping revealed DRB1-DQB1*0901
      *0303, a common susceptibility haplotype in Japanese patients with type 3 APS or
      acute-onset type 1 diabetes. The combination of variant type 3 APS and PAH is
      extremely rare and to the best of knowledge, this is the first case reported in a
      Japanese patient.

PMID- 29459558
TI  - [Duodenal mucosal defense mechanisms;Current update on 'Duodenology'].

PMID- 29459559
TI  - [Histogenesis of duodenal non-ampullary tumor-like lesions and tumors].

PMID- 29459560
TI  - [Cutting edge of endoscopic diagnosis and treatment for duodenal tumors].

PMID- 29459561
TI  - [Duodenum plays the certain roles in functional gastrointestinal disorders].

PMID- 29459562
TI  - [The impact of direct-acting antiviral therapy on the diagnosis of hepatitis-C
      virus-associated hepatocellular carcinoma].
AB  - Since the introduction of direct-acting antiviral (DAA)-based combination
      therapies in September 2014 for patients with chronic hepatitis-C (CH-C),
      numerous patients have been diagnosed with hepatitis-C virus (HCV)-associated
      hepatocellular carcinomas (HCCs) during the screening performed prior to DAA
      therapy. The present study was conducted on the antiviral therapy for CH-C in two
      phases:i) the interferon (IFN) phase between January 2011 and August 2014 and ii)
      the DAA phase between September 2014 and September 2016. During the DAA phase,
      HCCs were detected in eight patients who were referred to our hospital for anti
      HCV therapy. In contrast, HCCs were detected in only two patients during the IFN
      phase. The number of patients with newly detected HCC in the DAA phase (20.5%)
      who were referred for the anti-HCV therapy was significantly higher than that in
      the IFN phase (1.7%). Owing to the high efficacy and safety of the DAA therapy,
      the number of patients referred to our hospital for anti-HCV therapy increased
      from 40.5 persons/year in the IFN phase to 80.3 persons/year in the DAA phase.
      The average ages of patients in the DAA and IFN phases were 68 and 61 years,
      respectively. The increase in the number of patients with newly detected HCC
      referred for the anti-HCV therapy in the DAA phase could be attributed to the
      increase in the number of referred patients for anti-HCV therapy and the aging of
      these patients in the DAA phase. All the eight patients with newly detected HCC
      who were referred for anti-HCV therapy in the DAA phase received curative
      treatments. The median age, rate of liver cirrhosis, and median tumor size of the
      patients were 69 years, 13%, and 16mm. Therefore, the findings of this study
      indicate that DAA therapies not only eradicate HCV infection but also contribute
      to the early diagnosis of HCC by encouraging the HCV-infected patients to visit
      hospitals and by promoting active network between hepatologists and family
      physicians.

PMID- 29459563
TI  - [A case of 8-cm metastatic lymph node rupture from early gastric cancer with low
      papillary structure].
AB  - A 79-year-old man experiencing sudden abdominal pain was admitted to our
      hospital. Upper gastrointestinal endoscopy and computed tomography images
      revealed an 8-cm lesion, suggestive of submucosal tumor in the gastric antrum and
      a type 0-IIc early gastric cancer in the gastric body. The tumor ruptured during
      preoperative examinations, which necessitated emergency D1+ distal gastrectomy.
      Pathological findings confirmed the penetration of the gastric cancer into the
      submucosa. The cancer comprised well-differentiated tubular carcinoma cells with
      a low papillary structure. At the submucosa, small clusters of carcinoma cells
      were surrounded by clear spaces. These clusters displayed a characteristic
      "inside out pattern" on immunohistochemical examination, suggesting that the
      clusters were probably incipient lesions of invasive micropapillary carcinoma.
      The ruptured tumor was identified as a lymph node metastasis from the gastric
      cancer. We herein report this extremely rare case in which lymph node metastasis
      from early gastric cancer enlarged and ruptured. The findings of this study
      suggest that the characteristic pathological type identified in this report,
      which signified high-grade malignancy, was associated with the rupture.

PMID- 29459564
TI  - [Retention of patency capsule in a patient with Crohn's disease].
AB  - A 40-year-old Japanese man with abdominal pain was referred to our hospital. The
      patient had been diagnosed with Crohn's disease at the age of 21 years and had
      since then received treatment with mesalazine and had been advocated an elemental
      diet. About 30 months before his visit to the hospital, he had swallowed a
      patency capsule, the retention of which in the ileum was subsequently detected on
      abdominal ultrasonography. The patient was advised to undergo the evaluation of
      stenosis, but he refused further investigation at that time. Computed tomography
      scanning performed at our institution revealed stenosis of the ileum and the
      presence of a high-density material in the proximal side of the stenosis. Double
      balloon enteroscopy and enterography with contrast media revealed multiple
      stenoses of the ileum. The stenotic ileum was surgically resected, and a foreign
      body was removed. Electron microscopy analysis revealed that the foreign body was
      the cellophane wall of the PillCamTM patency capsule. Thus, the retention of the
      cellophane wall of a patency capsule after consumption was diagnosed for the
      current case on the basis of the study findings.

PMID- 29459565
TI  - [Diagnosis of duplication of the sigmoid colon prior to surgery:a case study].
AB  - A 16-year-old woman identified with colonic distention using chest X-rays visited
      our hospital. Although abdominal computed tomography (CT), colonoscopy, and
      barium enema study indicated suspected duplication of the sigmoid colon, the
      exact portion of communication between the normal colon and the duplicated colon
      could not be determined. The patient was released, but followed up due to the
      lack of symptoms. After 7 months, she was urgently re-hospitalized due to the
      complaint of abdominal pain. Her abdominal CT revealed the wall thickness and
      distention of the duplication as well as voluminous stool containing barium.
      After the improvement of her symptoms and on the basis of the inflammatory
      findings, laparoscopic surgery was performed on the patient. Finally, the lesion
      was diagnosed as tubular- and continuous-type colonic duplication. Duplication of
      the colon is a relatively rare occurrence in adulthood. Herein, we report a case
      of duplication of the sigmoid colon diagnosed prior to surgery in an adult.

PMID- 29459566
TI  - [Successful endoscopic ultrasound-guided cyst drainage (EUS-CD) of pancreatic
      pseudocyst in the abdominal cavity to the cervical region accompanied by
      spontaneous rupture into the portal vein:a case study].
AB  - A 53-year-old man was admitted to our hospital with the complaint of neck pain
      and dyspnea. His blood examination revealed increased C-reactive protein and
      amylase levels. Enhanced computed tomography (CT) images demonstrated a
      retropharyngeal and a mediastinal low-density area extending to the portal area.
      He was diagnosed with pancreatic pseudocyst from the abdominal cavity to the
      cervical region accompanied by spontaneous rupture into the portal vein.
      Endoscopic ultrasound-guided cyst drainage (EUS-CD) of the most inferior cavity
      around the superior mesenteric artery was performed through the gastric wall. No
      adverse events were recorded during the procedure, and a near-complete resolution
      of his symptoms and the pseudocyst was achieved.

PMID- 29459567
TI  - A Giant Cardiac Cavernous Hemangioma Involving the Left Atrial Roof in an Elderly
      Woman.
AB  - Cardiac tumors are relatively rare, with primary hemangiomas being a particularly
      rare benign neoplasm. Herein, we report a case of a symptomatic cardiac tumor
      detected via echocardiography in an 82-year-old woman. Although we performed
      advanced imaging examinations for her heart, we could not diagnose the tumor
      before surgery. Eventually, a tumor involving the left atrial roof was detected,
      and it was completely resected to relieve her symptoms and establish a precise
      diagnosis. Histopathological examination indicated a cardiac cavernous
      hemangioma. The patient exhibited an uneventful recovery without any
      complications.

PMID- 29459568
TI  - Endovascular Repair of an Abdominal Aortic Aneurysm with Iliac Vein Compression
      Syndrome.
AB  - An 84-year-old man with chronic obstructive pulmonary disease (COPD) was referred
      to our institution for further treatment of severe swelling of the left lower
      extremity. The left iliac vein was compressed by the abdominal aortic aneurysm
      and a right common iliac arterial aneurysm measuring 62 mm and 45 mm in diameter
      and was partially thrombosed. Multiple pulmonary artery embolisms were also
      noted. Endovascular repair of the abdominal aortic aneurysm and the right common
      iliac arterial aneurysm was performed because of his respiratory dysfunction. The
      left leg edema gradually resolved after endovascular treatment. Six months after
      the treatment, computed tomography (CT) demonstrated resolution of the venous
      thrombus of the left lower extremity. Although open surgery is reliable treatment
      for iliac compression syndrome, endovascular treatment might be a feasible and an
      adequate therapeutic option for patients who have severe comorbidities,
      complications, or high frailties.

PMID- 29459571
TI  - Venous Branching Pattern in a Patient with Hemorrhagic Infarction in the Lingula
      after the Upper Division Resection of the Left Lung.
AB  - BACKGROUND: Because left upper division resection is similar to right upper
      lobectomy, this procedure is frequently employed. Few studies have used the
      anatomic courses of veins evaluated on preoperative computed tomography (CT)
      imaging to determine what types of patients are at the highest risk for
      hemorrhagic pulmonary infarction. CASE: We describe our experience with a patient
      in whom hemorrhagic pulmonary infarction occurred at 6 days after transecting two
      superior branches (V1 and V3) of the three branches of the left superior
      pulmonary vein. We preoperatively confirmed that small-caliber lingular veins
      were perfused by V3. However, the patient had a poor pulmonary function, and the
      tumor was located distal to V3. Left upper division resection was therefore
      performed. CONCLUSION: The division of V3 could be the cause of hemorrhagic
      infarction in the lingular segment after upper division segmentectomy.

PMID- 29459569
TI  - Selection of a Surgical Treatment Approach for Aortic Coarctation in Adolescents
      and Adults.
AB  - PURPOSE: Coarctation of the aorta (CoA) in adolescents and adults is relatively
      rare. Several operative techniques for CoA in adolescents and adults have been
      reported, but there is still no consensus. This study aims to highlight the use
      of individual patient characteristics to select optimal treatment strategies for
      CoA in adolescents and adults. METHODS: Surgical repair of CoA was performed in
      five patients (mean age: 34 +/- 14 years, range: 13-58 years). All patients had
      primary CoA, and one had aneurysm above the CoA. One patient had undergone
      previous aortic valve replacement (AVR) and graft replacement of the ascending
      aorta. One patient underwent resection of the coarctation without cardiopulmonary
      bypass (CPB) followed by direct end-to-end anastomosis. Three patients underwent
      CoA resection with an interposition graft through a lateral thoracotomy with
      partial CPB. One patient underwent AVR with extra-anatomical bypass (ascending
      descending aorta). RESULTS: No in-hospital deaths occurred, and there were no
      complications. During the follow-up period, there has been no recurrence of CoA.
      CONCLUSION: CoA in adolescents and adults is associated with different issues
      from those encountered in infant patients, and comprehensive surgery should be
      performed in all cases.

PMID- 29459570
TI  - Loss of Muscle Mass is a Novel Predictor of Postoperative Early Recurrence in N2
      Positive Non-Small-Cell Lung Cancer.
AB  - BACKGROUND: We often experienced early recurrence in patients with completely
      resected N2-positive non-small-cell lung cancer (NSCLC). Loss of muscle mass is a
      poor prognostic factor in patients with several stages of NSCLC. This study aimed
      to investigate the relationship between preoperative loss of muscle mass and
      postoperative early recurrence in patients with N2-positive NSCLC. METHODS: We
      retrospectively analyzed 47 male patients with completely resected pathological
      N2-positive NSCLC. Early recurrence was defined as that diagnosed within 1 year
      after the operation. We used the L3 muscle index (cross-sectional area of muscle
      at the L3 level, normalized for height) as a clinical measurement of loss of
      muscle mass (cutoff value, 52.4 cm2/m2). RESULTS: In all, 18 patients with early
      recurrence had significantly poorer outcomes compared with those without (P
      <0.01). In univariate analysis, loss of muscle mass (P = 0.023), carcinoembryonic
      antigen (CEA) level >5.0 ng/mL (P = 0.002), and absence of postoperative
      chemotherapy (P = 0.042) were predictors of postoperative early recurrence. In
      multivariate analysis, loss of muscle mass (P = 0.004) and CEA level >5.0 ng/mL
      (P = 0.001) were independent predictors. CONCLUSIONS: Loss of muscle mass is an
      independent predictor of postoperative early recurrence in pathological N2
      positive NSCLC patients.

PMID- 29459572
TI  - A Rare Case of Multiple Myxoma Involving Both Mitral Valve Leaflets.
AB  - Mitral valve myxoma is a very rare entity. Multiple myxomas with extensive
      involvement of the anterior and posterior leaflets of the mitral valve are
      exceedingly rare. We report a 58-year-old man who was admitted as sudden syncope.
      Thoracic echocardiography showed several masses adherent to the anterior and
      posterior leaflets and the mitral annulus with obvious mobility. Intraoperative
      probing revealed multiple tumors attached to the mitral annulus, valve leaflets,
      and tendinous cords. Mechanical mitral valve replacement was performed.
      Histopathological examination confirmed all tumors to be myxomas.

PMID- 29459573
TI  - Potential Role of ASC, a Proapoptotic Protein, for Determining the Cisplatin
      Susceptibility of Lung Cancer Cells.
AB  - Primary lung cancer is the most frequent cause of cancer-related deaths
      worldwide. Cisplatin has been used as a key drug in the treatment for patients
      with lung cancer; however, most of the patients failed to respond to cisplatin
      within several months, and the mechanisms underlying the cisplatin resistance
      have not been fully elucidated. Apoptosis-associated speck-like protein
      containing a caspase recruitment domain (ASC) is a key adaptor protein in the
      formation of inflammasomes. ASC is also involved in apoptotic signaling.
      Importantly, ASC expression is decreased in lung cancer and various cancers, but
      its precise function in tumor progression remains unknown. To explore the
      hitherto unknown role of ASC in lung cancer, we initially searched for lung
      cancer cell lines with higher expression levels of ASC using Cancer Cell Line
      Encyclopedia (CCLE) database, thereby identifying the A549 human non-small cell
      lung cancer cell line. Accordingly, with retroviral shRNA, the expression of ASC
      was forced to decrease in A549 cells. Stable ASC-knockdown cells, thus
      established, showed the increased activities of proliferation, motility, and
      invasion, compared with control cells. Importantly, ASC-knockdown cells also
      became resistant to cisplatin, but not to other anti-cancer agents, 5
      fluorouracil and paclitaxel. Bcl-2 and phospho-Src levels were increased in ASC
      knockdown cells. A Bcl-2 inhibitor, ABT-199, induced an apoptotic response in ASC
      knockdown cells, and dasatinib, a Src inhibitor, blocked cell invasiveness. Thus,
      ASC may be involved in tumor suppression and cell death via Bcl-2 and pSrc.
      Targeting Bcl-2 and Src in ASC-downregulated populations of lung cancer may
      improve treatment outcome.

PMID- 29459574
TI  - Comparison of surgical outcomes after pneumonectomy and pulmonary function
      preserving surgery for non-small cell lung cancer.
AB  - BACKGROUND: According to previous reports, lobectomy with bronchoplasty or
      angioplasty is a more feasible surgery than pneumonectomy for central-type non
      small cell lung cancer. However, few studies have compared both the short- and
      long-term outcomes between pneumonectomy and pulmonary function-preserving
      surgery. METHODS: From January 2004 to December 2015, 18 patients underwent
      pneumonectomy (Group PN) and 12 patients underwent pulmonary function-preserving
      surgery (group PS) at Fukushima Medical University Hospital. Clinicopathological
      factors were statistically compared between the two groups. RESULTS: The
      operation times in Group PN and Group PS were 285.9+/-27.9 and 271.3+/-99.2 min,
      respectively (p=0.613), while the amounts of intraoperative bleeding were 324.8+/
      248.9 and 164.5+/-116.6 g, respectively (p=0.020). The duration of chest drainage
      and hospitalization after surgery in both groups were not significantly different
      but there was a tendency toward shorter periods of these durations in Group PS.
      The 5-year disease-free survival (DFS) rate in Group PN and PS was 51.4% and
      74.1%, respectively, without a significant difference (p=0.298). The 5-year
      overall survival (OS) rate in Group PN and PS was 52.5% and 56.6%, respectively,
      also without a significant difference (p=0.748). The 5-year OS rate was inferior
      to the 5-year DFS rate in Group PS, and the 5-year OS rate was not better than
      the 5-year DFS rate in Group PN. CONCLUSIONS: The short-term results were better
      in Group PS than PN. However, the long-term results in both groups were similar.
      Other causes of death influenced OS in both groups; this result might have been
      affected by the surgical procedures.

PMID- 29459575
TI  - Difficult Stentablation with an Episode of Stuck and Entrapped Burr within the
      Underexpanded Stent.
AB  - Stentablation by rotational atherectomy has been reported as an option to correct
      underexpanded stents. Due to concerns of excessive stent damage, distal
      embolization of metal particles, excessive heat generation, and burr entrapment
      in the stent, stentablation has been considered the last choice to manage
      underexpanded stents. Here, we report a case of a stuck and entrapped atherectomy
      burr inside an underexpanded and undilatable stent, which made withdrawal of
      therotablation burr during rotational atherectomy difficult. After successful
      stentablation by rotational atherectomy, we were able to complete the
      percutaneous coronary intervention with another stent.

PMID- 29459576
TI  - A High Level of Blood Urea Nitrogen Is a Significant Predictor for In-hospital
      Mortality in Patients with Acute Myocardial Infarction.
AB  - High levels of blood urea nitrogen (BUN) have been demonstrated to significantly
      predict poor prognosis in patients with acute decompensated heart failure.
      However, this relationship has not been fully investigated in patients with acute
      myocardial infarction (AMI). We investigated whether a high level of BUN is a
      significant predictor for in-hospital mortality and other clinical outcomes in
      patients with AMI. The Japanese registry of acute Myocardial INfarction diagnosed
      by Universal dEfiniTion (J-MINUET) is a prospective, observational, multicenter
      study conducted in 28 institutions, in which 3,283 consecutive AMI patients were
      enrolled. We excluded 98 patients in whom BUN levels were not recorded at
      admission and 190 patients who were undergoing hemodialysis. A total of 2,995
      patients were retrospectively analyzed. BUN tertiles were 1.5-14.4 mg/dL (tertile
      1), 14.5-19.4 mg/dL (tertile 2), and 19.5-240 mg/dL (tertile 3). Increasing
      tertiles of BUN were associated with stepwise increased risk of in-hospital
      mortality (2.5, 5.1, and 11%, respectively; P < 0.001). These relationships were
      also observed after adjusting for reduced estimated glomerular filtration rate
      (estimated GFR < 60 mL/minute/1.73 m2) or Killip classifications. In
      multivariable analysis, high levels of BUN significantly predicted in-hospital
      mortality, after adjusting for creatinine and other known predictors (BUN tertile
      3 versus 1, adjusted odds ratio [OR]: 2.59, 95% confidence interval [95% CI]:
      1.57-4.25, P < 0.001; BUN tertile 2 versus 1, adjusted OR: 1.60, 95% CI: 0.94
      2.73, P = 0.081). A high level of BUN could be a useful predictor of in-hospital
      mortality in AMI patients.

PMID- 29459577
TI  - Women among First Authors in Japanese Cardiovascular Journal.
AB  - The representation of women in Japanese academic medicine is not evident. We
      aimed to assess trends related to the proportion of female first authors in
      Japanese cardiovascular journals.We reviewed original research articles in 6
      journals published in English by Japanese societies between 2006 and 2015 related
      to cardiovascular fields. We conducted a multivariable logistic regression
      analysis to assess the factors associated with the gender of first authors and
      plotted the trend of predicted probability for female first authors over the
      study period. Of 7,005 original articles, 1,330 (19.0%) had female first authors.
      Affiliations located in Japan (adjusted odds ratio [aOR], 0.76; 95% confidence
      interval [CI], 0.71-0.81), concurrent first and corresponding authors (aOR, 0.69;
      95% CI, 0.64-0.74), and the total number of listed authors (aOR, 0.97; 95% CI,
      0.95-0.99) were negatively associated with female first authors. The adjusted
      probability of a female first author increased from 13% to 20% on an average
      between 2006 and 2009, but the increase reached a plateau after 2010.Female first
      authors of original research articles published in Japanese cardiovascular
      journals increased over the examined decade. However, the representation of women
      is still low and has plateaued in recent years. A gender gap in authorship for
      Japanese cardiovascular journals remains.

PMID- 29459578
TI  - Trapping Balloon Technique for Removal of the Burr in Rotational Atherectomy.
AB  - Because rotational atherectomy (RA) has several unique complications, such as
      burr entrapment, vessel perforation, and slow flow, it is important for
      interventional cardiologists to be familiar with bailout procedures for such
      complications. The principal part of bailout procedures is to keep a guidewire in
      the target coronary artery during the procedure. However, it is not easy to keep
      a guidewire in the same position during the removal of a burr because the length
      of the RA guidewires is 300 cm, and the removal of a burr requires collaboration
      between the primary operator and an assistant. We describe the case of an 83-year
      old male with stable angina. We performed RA to the left anterior descending
      artery, and removed the burr using a KUSABI (Kaneka Medix Corporation, OSAKA,
      Japan) trapping balloon technique without activating the dynaglide mode. This
      simple technique would help RA operators remove a burr more reliably than the
      conventional removal technique.

PMID- 29459579
TI  - Neonatal Leukemoid Reaction with Fetal Inflammatory Response Syndrome Is
      Associated with Elevated Serum Granulocyte Colony Stimulating Factor and
      Interleukin-6.
AB  - Leukemoid reaction (LR) is a reactive disease that exhibits abnormal blood values
      similar to leukemia, but not due to leukemia. One report showed that neonatal LR
      (NLR) was associated with elevated serum granulocyte colony stimulating factor (G
      CSF) in only 30% of the study neonates. NLR is not always associated with the
      elevation of serum G-CSF. NLR was defined as a white blood cell count of >= 40 *
      103/MUL and/or blast cell concentration of > 2%. We have focused on NLR with
      fetal inflammatory response syndrome (FIRS), defined as a fetal systemic
      inflammatory reaction triggered by intrauterine infection. FIRS was diagnosed
      based on a cord serum interleukin-6 (IL-6) concentration >= 17.5 pg/mL and
      histopathological chorioamnionitis. Because NLR is highly associated with FIRS,
      we have hypothesized that NLR is associated with the elevation of both G-CSF and
      IL-6. This is the first report to measure multiple cytokines in NLR at the same
      time. The study comprised 19 preterm infants with FIRS: 8 with NLR (study group)
      and 11 without NLR (control group). Serum G-CSF and IL-6 concentrations were
      significantly higher in the study group than the control group. There was a
      positive correlation between G-CSF and IL-6 levels in the study group but not in
      the control group. These results suggest that elevated serum G-CSF and IL-6 may
      underlie NLR. Thus, G-CSF and IL-6 concentrations may be predictive of the onset
      of NLR. Measuring these cytokines is useful for judging the prognosis of preterm
      infants and for their post-natal clinical management.

PMID- 29459580
TI  - Research on the axial velocity change rule of desktop slot exhaust hood.
AB  - The desktop slot exhaust hood has been widely used, but it is calculated by
      empirical formula. Axial velocity change rule of desktop slot exhaust hood can
      effectively provide the basis of the wind speed needed in order to control the
      poison. According to gas motion mathematical model, the geometry model and
      boundary conditions of desktop slot exhaust hood was established, and the
      influence of the hood sizes to axial velocity were analyzed by Fluent simulation.
      The changes of relationship between the axial velocity (V) and the distance from
      the hood mouth (L), the short edge of the hood mouth (a), the long edge of the
      hood mouth (b), the equivalent diameter of the hood mouth (d) and the square root
      of the hood mouth area (?A) were comparative analyzed by dimensionless
      processing. The result is the V/V0 with L/d have better change rule. The axial
      velocity change rule of different axial velocity were also analyzed using V/V0
      with L/d change rule, and the change rule of V/V0 with L/d of desktop slot
      exhaust hood was obtained, which was verified by experiment.

PMID- 29459581
TI  - Predictors of Alcohol Relapse Following Liver Transplantation for Alcohol-Induced
      Liver Failure. Consideration of "A-D" Selection Criteria.
AB  - Demonstrated abstinence from alcohol for over six months and successful
      completion of a formal alcohol addictions program are two commonly employed
      criteria for determining whether an alcoholic patient with liver failure should
      proceed to liver transplantation. In this systematic review of the medical
      literature, we review the justification for these criteria and consider other
      variables that have also been reported to be of predictive value. While
      abstinence from alcohol for over six months is supported by the medical
      literature, data are more limited regarding the value of formal alcohol
      addictions program as selection criteria for proceeding towards liver
      transplantation. Positive family histories of alcoholism, co-inhabitants drinking
      alcohol in the presence of the patient and concurrent drug dependencies are more
      robust predictor variables of post-transplant recidivism. Based on the findings
      of this review, we propose a simple A-D transplantation selection criteria
      wherein "A" refers to demonstrated abstention from alcohol for over six months,
      "B" biology (a negative family history for alcoholism), "C", co-inhabitants not
      consuming alcohol in the presence of the patient; and "D", no concurrent drug
      dependency.

PMID- 29459582
TI  - Paeoniflorin Inhibits Receptor Activator for Nuclear Factor kappaB (RANK) Ligand
      Induced Osteoclast Differentiation In Vitro and Particle-Induced Osteolysis In
      Vivo.
AB  - BACKGROUND Paeoniflorin (PF), a glucoside isolated from the dried root of Paeonia
      lactiflora Pall, has been reported to have a number of pharmacological
      properties, including immunity-regulation, anticancer activities, and
      neuroprotective effect. However, PF's pharmacological role in bone disorder has
      been seldom reported. Hence, this study was designed to investigate the effects
      of PF on osteoclast differentiation and osteolysis diseases. MATERIAL AND METHODS
      The bone marrow macrophages were isolated from C57BL/6 mice and incubated with
      RANK ligand (RANKL) and various concentrations of PF. After 5 days of incubation,
      tartrate-resistant acid phosphatase (+) cells and bone resorption pits were
      counted. Effects of PF on expression of osteoclast-specific protein and gene were
      investigated via Western blot, q-PCR, and immunofluorescence assay. The
      osteoprotective effect of PF in vivo was evaluated in a calvarial osteolysis
      model via micro-CT scan and histological stain. RESULTS In vitro, PF intervention
      inhibited osteoclast formation and resorption activity. PF also impaired RANKL
      induced NF-kappaB phosphorylation and immigration to the nucleus. PF suppressed
      osteoclast-marker protein and gene expression. In vivo, PF inhibited cobalt
      chromium-molybdenum alloy particle-induced osteolysis and reduced osteoclast
      number in tissue slice. CONCLUSIONS PF is a potential agent against osteolysis
      related diseases caused by excessive osteoclast activity.

PMID- 29459584
TI  - Study on Hemoglobin Concentration in Patient with Chronic Kidney Disease.
AB  - In the present study hemoglobin concentration were estimated in chronic kidney
      diseased patient to observe the frequency of low hemoglobin level in chronic
      kidney diseased (CKD) patient and to assess the incidence of anaemia. This cross
      sectional study was carried out in the department of Physiology of Mymensingh
      Medical College, Mymensingh, Bangladesh from July 2014 to June 2015. For this
      purpose, total 200 subjects with age ranged from 25 to 60 years were selected and
      divided into100 healthy persons as control group and 100 CKD patients as study
      group. Both control and study group were further divided into 50 male and 50
      female. Hemoglobin concentration was evaluated by the Cyanmethemoglobin (CMG)
      method. Statistical analysis of data was done by unpaired student's 't' test. The
      results showed that hemoglobin levels decreased significantly in chronic kidney
      diseased patients than the normal healthy persons. The decreasing frequency of
      hemoglobin level in CKD may predispose the patients to anemia and increasing the
      other complications.

PMID- 29459585
TI  - Ultrasonographic Evaluation of Malignant Pediatric Abdominal Tumour with
      Histopathological Correlation.
AB  - Ultrasonography is a very useful diagnostic tool to evaluate pediatric abdominal
      mass. This cross sectional study was conducted among clinically suspected
      patients having malignant abdominal mass attending in the department of Radiology
      & Imaging, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from
      January 2008 to December 2009. Total 56 patients were included in this study.
      Patients were scanned by high resolution gray scale ultrasonography of the
      abdominal masses. After surgical procedure, biopsy specimen were collected in a
      container containing 10% formalin and sent for histopathological examination.
      Mean age of the patients group was 5.91 years with a standard deviation of +/
      3.21 years. All patients were within 2 to 13 years age. Out of all patients, male
      were 33(58.9%) and 23(41.1%) were female. Male and female ratio was 1.4:1.
      Ultrasonographic diagnosis as Wilm's tumour were 27(48.2%), hepatoblastoma
      8(14.3%), lymphoma 7(12.5%), neuroblastoma 6(10.7%), suspected malignancy
      6(10.7%) and lastly teratoma were 2(3.6%). Sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV) and accuracy of
      ultrasonography in the evaluation of Wilm's tumour were 100.0%, 90.6%, 88.9%,
      100.0% and 94.6% for neuroblastoma 83.3%, 98.0%, 83.3%, 98.0% and 96.4% for
      lymphoma 83.3%, 96.0%, 71.4%, 98.0% and 94.6% and for hepatoblastoma 100.0%,
      100.0%, 100.0%, 100.0% and 100.0% respectively. It is a noninvasive and cost
      effective modality. Carefully performed ultrasonographic study would give
      reliable and accurate information needed in the diagnosis of abdominal malignancy
      in children.

PMID- 29459583
TI  - Ruptured Cystic Artery Pseudoaneurysm Successfully Treated with Urgent
      Cholecystectomy: A Case Report and Literature Review.
AB  - BACKGROUND Cystic artery pseudoaneurysm is rare, and some cases are associated
      with inflammation of the gallbladder. There is limited information regarding this
      condition, and the clinical features remain unclear. This report is a case of
      ruptured cystic artery pseudoaneurysm diagnosed by computed tomography (CT)
      imaging and treated with urgent cholecystectomy and is supported by a literature
      review of previous cases. CASE REPORT A 90-year-old man, who had developed acute
      cholecystitis due to a gallstone one month previously, was referred to our
      hospital. He developed fever and epigastric pain while waiting for a scheduled
      elective cholecystectomy. Laboratory investigations showed elevated markers of
      inflammation and elevated hepatobiliary enzyme levels. Computed tomography (CT)
      imaging showed cholecystitis and pseudoaneurysm of the cystic artery. The
      pseudoaneurysm had ruptured and was accompanied by the formation of a hematoma
      within the gallbladder that involved the liver bed. Having made the preoperative
      diagnosis, an urgent open laparotomy was performed, during which the gallbladder
      was found to have perforated. The hematoma penetrated into the liver bed.
      Cholecystectomy was performed, and the pseudoaneurysm of the cystic artery was
      extirpated. There were no serious postoperative complications. A literature
      review identified 50 previously reported case of cystic artery pseudoaneurysm.
      CONCLUSIONS A case of ruptured cystic artery pseudoaneurysm, successfully treated
      with urgent cholecystectomy is reported, supported by a literature review of
      previous cases and characterization of the clinical features of this rare
      condition.

PMID- 29459586
TI  - Risk Factors and Immediate Neonatal Outcome of Multiple Pregnancies in a SCANU of
      A Tertiary Care Hospital, Bangladesh.
AB  - Multiple pregnancies are a significant risk factor for maternal and perinatal
      morbidity due to inherent biological risks. The present study was aimed to
      determine the risk factors and to evaluate the immediate neonatal outcome of
      multiple pregnancies. This descriptive observational study was conducted in the
      newly established Special Care Neonatal Unit (SCANU) of Mymensingh Medical
      College Hospital (MMCH), Bangladesh from January 2015 to March 2015. Total 86
      newborns of multiple pregnancies who were admitted during the study period were
      included in the study. Among them 34 pairs were twin, and 6 sets of triplets were
      present. Among all infants in the study 79.1% were twin and 20.9% were triplet.
      According to our observation most of the mother aged between 20-29 years (67.5%)
      and majorities of them were multi-para (62.5%). Preterm delivery occurred in
      70.0% cases. 75% newborns were delivered by caesarian section and remaining by
      vaginal route. The most common risk factors in present study are use of ovulation
      induction drugs (52.5%) for sub fertility followed by family history of multiple
      gestations. In 35.0% cases we did not find any cause. Common morbidities of the
      infants were preterm low birth weight (95.3%), neonatal jaundice (81.3%), RDS
      (34.8%), perinatal asphyxia (PNA) (17.4%), neonatal sepsis (25.0%) and congenital
      anomalies (23.2%). Mortality rate of twin was 30% and for triplets it was 50%.
      Among total study population mortality rate was 30.2%. Main causes of mortality
      was preterm low birth weight (76%), RDS (57.6%), septicaemia (26%), PNA (19.0%).
      Morbidities and mortalities in infants of multiple pregnancies are observed much
      higher than singleton pregnancy. We hope that in light of our findings regarding
      risk factors like assisted reproduction and their consequences over mother and
      newborn, periodic reviews will be done in future to reduce the incidence and the
      unfavourable outcome of multiple pregnancy.

PMID- 29459587
TI  - The Pattern of Serum Calcium, Phosphate and Parathyroid Hormone Levels in Pre
      Diagnosed Chronic Kidney Disease Patients.
AB  - Chronic kidney disease (CKD) is an international health problem affecting 5-10%
      of the world population. Patients with chronic kidney disease were known to have
      higher prevalence of changes in serum calcium, phosphate and parathyroid hormone
      in Western countries, but data on the impact of CKD on serum calcium, phosphate
      and parathyroid hormone in our country are scarce. This cross-sectional type of
      descriptive study was conducted in the Department of Medicine, Mymensingh Medical
      College Hospital, Mymensingh, Bangladesh from March 2016 to September 2016. The
      aim of this study is to estimate serum calcium, phosphate and parathyroid hormone
      levels in chronic kidney disease (CKD) patients for early recognition of
      abnormalities, understanding of their patho-physiological consequences & planning
      management strategies to prevent their progression, thus reducing the morbidity &
      mortality. This study shows Hypocalcemia, hyperphosphataemia and elevated serum
      PTH levels are noted in later CKD stages & worsen with disease progression.

PMID- 29459588
TI  - Magnetic Resonance Imaging in Evaluation of Sinonasal Masses with
      Histopathological Correlation.
AB  - Sinonasal mass is the abnormal growth of tissue from nasal cavity and mucosa of
      the paranasal sinuses. The growth may be benign or malignant. The benign lesion
      grows slowly and does not metastasize. The malignant lesion grows rapidly and
      metastasizes early. The aim of this study is to evaluate and diagnose the various
      types of sinonasal masses with MRI and its correlation with histopathological
      findings. This cross sectional descriptive study was carried out for a period of
      02 years, from July 2015 to June 2017. The patients were selected from the ENT
      outpatient department and from the department Radiology & Imaging of Mymensingh
      Medical College Hospital, Mymensingh, Bangladesh who were reported as case of
      sinonasal masses. Thirty three (33) patients (17 males and 16 females) with
      sinonasal masses were included after fulfilling exclusion & inclusion criteria
      which was confirmed by proper clinical examination & were subjected to MRI and
      histopathological examination. The age range was 11 to 85 years. The nasal cavity
      was the most commonly involved site with sinonasal malignancies (were 4 cases,
      12.12%) followed by the maxillary sinuses (were 2 cases, 6.06%). The least
      commonly affected site was the frontal sinuses (was 1 case, 3.03%).
      Histopathological findings shows benign sinonasal tumors were present in 25
      cases. The most common benign lesion was sinonasal polyposis 10 cases (30.30%),
      followed by inverted papilloma 6 cases (18.18%) & juvenile nasopharyngeal
      angiofibroma 6 cases (18.18%), adenoma 02 cases (6.06%), and one case was
      rhinosporidiosis (3.03%). Malignant sinonasal tumors were present in 8 cases.
      Most common malignant tumors were nasopharyngeal carcinoma in 4 cases (12.12%),
      adenoid cystic carcinoma in 3 cases (9.09%) and non-Hodgkin lymphoma was present
      in 01 case (3.03%). MRI report shows benign masses in 23 cases of which
      nasopharyngeal polyposis was 10(30.30%), inverted papilloma 6(18.18%), juvenile
      angiofibroma 4(12.12%), adenoma 02(6.06%) & rhinosporidiosis 1(3.03%). Among 10
      malignant tumors nasopharyngeal carcinoma were 6(18.18%), adenoid cystic
      carcinoma 3(9.09%) & non-Hodgkin lymphoma 1(3.03%). MRI findings of malignant
      sinonasal masses revealed that sensitivity 87.5%, specificity 40.0%, positive
      predictive value (PPV) 70% & negative predictive value 66%. Statistically
      significant association was observed between histopathology & MRI findings, p
      value was 0.305. Statistically significant association was found between
      histopathology & MRI findings.

PMID- 29459589
TI  - Interaction between Hypertension and Asthma in Adult.
AB  - Asthma has been defined as a chronic inflammatory disorder of the airways that is
      associated with recruitment of inflammatory cells and the clinical development of
      wheezing, shortness of breath, chest tightness, and cough. The prevalence of
      asthma increased steadily over the latter part of the last century, first in the
      developed and then in the developing world. Current estimates suggest that asthma
      affects 300 million people worldwide, with a predicted additional 100 million
      people affected by 2025. This cross sectional study was conducted from January
      1999 to August 1999 on 5642 Bangladeshi people and another same study carried out
      from November 2009 to April 2010 on 8088 subjects. In 1999 the prevalence of
      asthma was 6.9% whereas in 2010 it is 6.96%. Both asthma and hypertension are
      spastic disorders of smooth muscle, there is the similarities between these two
      diseases may predispose the individuals with one disease to the other. This
      descriptive type of cross-sectional study was done to find the Interaction
      between hypertension and asthma in adult and carried out in the Department of
      Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from July 2014 to
      January 2016. Fifty (50) male and fifty (50) female adult asthmatic patients aged
      18-60 years were included in the study group. They are enrolled from the
      Department of Medicine, Mymensingh Medical College, Mymensingh and also from
      locality. For comparison age matched 50 male and 50 female apparently healthy
      persons were also studied as control. Blood pressure was estimated by
      auscultatory method by sphygmomanometer. For statistical analysis unpaired
      student's 't' test was used. Mean blood pressure were significantly increased in
      study group in comparison to control group and the result was statistically
      significant (p<0.001). The study findings showed a high prevalence of
      hypertension among asthmatic patients than non asthmatic healthy persons. From
      this study, it may be concluded that hypertension and asthma are closely
      connected.

PMID- 29459590
TI  - Skin Biopsy and Histopathological Diagnosis of Dermatological Diseases.
AB  - Microscopic examination of skin and mucous membrane is an established
      investigation in diagnosis and follow up of many dermatological conditions
      frequently encountered during practice. Histopathological examination is
      performed with biopsied specimen from skin and or mucous membrane where required.
      However neither do all skin biopsies produce neither a conclusive diagnosis nor
      the dermatologists routinely perform this procedure to every patient they
      consult. This cross sectional descriptive study conducted by reviewing the
      records of all biopsied cases studied for histopathology in Mymensingh Medical
      College, Mymensingh and Shaheed Mansur Ali Medical College, Dhaka, Bangladesh
      from January 2012 to December 2016. The aim of this study was to investigate the
      favourable clinical diagnoses set by dermatologists when performing skin biopsy,
      the diagnoses reached by the dermatopathologists after microscopic examination,
      and the relationship between them and finally to comment on the instances that
      skin biopsy fails to fulfill the diagnostic task. Fourteen hundred and thirty six
      (1436) cases of skin biopsy were reviewed and descriptive statistics were
      performed. Maximum cases 39.1% (562) were in 2nd decade with almost equal sex
      distribution. The most frequently proposed clinical diagnoses included
      papulosquamous dermatoses 28.6% (410), whereas histological confirmation was in
      13.1% (188). Histological diagnosis was more as nonspecific dermatitis 31.6%
      (454). After microscopic examination, a specific histological diagnosis was found
      in 83.5% (1199) of the cases and a consensus between clinical and histological
      diagnoses was observed in 69.2% (994). Neither histological diagnosis nor any
      feature consistent with clinical suspicion was observed in 10.1% (145) cases.
      Histopathological examination of skin biopsy is still a valuable diagnostic tool
      in many skin diseases and dermatoses with diagnostic dilemma. There are cases in
      which diagnostic inefficiency are being faced even after skin biopsy examination.

PMID- 29459591
TI  - Correlation of Ball Circumference with Body Weight in 5-10 Years Aged Bangladeshi
      Children.
AB  - This cross sectional, descriptive and analytic study was conducted among 5-10
      years aged 109 Bangladeshi children (70 male and 39 female) at different areas of
      Mymensingh district (Fulpur, Muktagacha, Fulbaria, Trisal and Haluaghat),
      Bangladesh from January 2016 to December 2016. Sample collection was done by
      nonrandom purposive sampling technique. Any kind of congenital and acquired foot
      deformity was excluded to construct standard measurement. The present
      anthropometric study was designed to construct data of 5 to 10 years aged
      Bangladeshi children regarding ball circumference, to measure its correlation
      with body weight and this attempt has been made out to grow interest among the
      researchers for future study and also to compare the data with the data of the
      people of other races. Weight of the subject was measured with the digital
      weighing machine and ball circumference was measured using flexible measuring
      tape. The children were asked to stand with weight distributed equally on both
      feet. The legs were perpendicular to the feet. The mean ball circumference of
      right side of 5, 6, 7, 8, 9 and 10 years aged male were 16.93+/-1.05cm, 17.00+/
      0.72cm, 18.10+/-1.28cm, 18.33+/-.99cm, 19.37+/-1.12cm and 19.94+/-1.30cm
      respectively and those of female were 16.27+/-1.10cm, 16.85+/-0.59cm, 17.44+/
      0.92cm, 18.02+/-0.82cm, 18.00+/-1.58cm and 19.23+/-1.40cm respectively. The mean
      ball circumference of left side of 5, 6, 7, 8, 9 and 10 years aged male were
      16.86+/-1.05cm, 16.94+/-.70cm, 18.02+/-1.29cm, 18.26+/-.99cm, 19.27+/-1.12cm and
      19.87+/-1.29cm respectively and those of female were 16.18+/-1.10cm, 16.77+/
      0.62cm, 17.36+/-0.92cm, 17.98+/-0.87cm, 17.90+/-1.58cm and 19.13+/-1.40cm
      respectively. In this study on both sides, ball circumference showed non
      significant positive correlation with body weight in 5 years old male and female,
      6 years old male and female, 7 years old male and female, 8 years old female, 9
      years old male and female and 10 years old male and female. In case of 8 years
      old male, it showed non-significant negative correlation with body weight.

PMID- 29459592
TI  - Current Trends of Using Systemic Antifungal Drugs and their Comparative Efficacy
      in Tinea Corporis and Tinea Cruris in Outpatient Department of Dermatology in a
      Tertiary Level Hospital.
AB  - Tinea corporis & cruris are one of the earliest known fungal infection and are
      very common throughout the world. Although tinea corporis and tinea cruris does
      not cause mortality but causes morbidity and poses a major health problem. This
      study was conducted to evaluate the Comparative Efficacy of Terbinafine and
      Fluconazole in the Treatment of Tinea corporis and Tinea cruris. This cross
      sectional comparative type of analytical study was carried out at the department
      of Pharmacology & Therapeutics with collaboration of Dermatology and Venereology
      in Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2016
      to December 2016. In this study 168 newly diagnosed Tinea corporis and Tinea
      cruris patient was purposively selected where pattern of comparative efficacy of
      terbinafine and fluconazole were analyzed. Among 168 patients most of the
      patients presented with tinea corporis (58.33%). Most patients belong to 21-30
      years age group. Male female ratio in this study was 1.15:1. In this study 143
      patients were treated by fluconazole 50mg once daily for 4 weeks and 25 patients
      were treated by terbinafine 250 mg once daily for 4 weeks. After 4 weeks,
      improvement rate by fluconazole was 86.02% and terbinafine 96.00%. The clinical
      score of both groups after 4th week of treatment, there was slight more reduction
      of clinical score in terbinafine using group than fluconazole using group. The
      difference between these two clinical score was not statistically significant
      (p>0.05). Although no significant difference was observed between these two
      groups of patient in clinical aspect, but due to its lower price and availability
      in the hospital, it is suggested that fluconazole is more suitable for the
      treatment of tinea corporis and tinea cruris.

PMID- 29459593
TI  - A study on the Effect of Captopril on Gentamicin Induced Nephrotoxicity in Rats.
AB  - An experimental study was carried out to evaluate the effect of Captopril on
      Gentamicin induced nephrotoxicity in rats in the Department of Pharmacology,
      Mymensingh Medical College and Dhaka Medical College, Bangladesh. Gentamicin
      antibiotic is most commonly employed clinically because of their potent
      bactericidal activities against Gram negative bacterial infections, less
      bacterial resistance, post-antibiotic effects and low cost. Gentamicin is
      associated with an induction of slow rises in serum creatinine, inflammation and
      perivascular edema, tubular degeneration and necrosis, tubular debris collection,
      glomerular atrophy which ultimately show the way to renal dysfunction. In spite
      of continued attractive efforts during the last decade, antioxidants like
      medicinal plants and different classes of drugs which were promised to reduce or
      ameliorate Gentamicin induced nephrotoxicity is yet a matter of debate. This
      study was aimed at inducing nephrotoxicity by injection Gentamicin and estimating
      the renal damage biochemically by measuring serum creatinine and perform
      histopathology of renal cortex in support of biochemical findings both in control
      groups, nephrotoxic and Captopril treated rats; also to determine the comparison
      between the concomitant and post effects of Captopril on control and nephrotoxic
      rats and to estimate the effect of Gentamicin withdrawal, 7 days after last
      injection in rats.

PMID- 29459594
TI  - Evaluation of Intraoral Burning Sensation in Response to Heat-Cured and Self
      Cured Acrylic Resin Denture Base Material.
AB  - The objective of this prospective experimental clinical trial was to evaluate
      intraoral burning sensation in response to heat-cured and self-cured acrylic
      resin denture base material and carried out in the department of Prosthodontics
      of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from February
      2014 to September 2015. Forty eight patients were evaluated in this study; of
      them 35(72.92%) patients were male and 13(27.08%) patients were female with age
      range from 24 to 70 years. In this study 48 patients were evaluated in term of
      burning sensation, of them 24 patients were provided with heat-cured acrylic
      resin denture and were considered as Group A and 24 patients were provided with
      self-cured acrylic resin denture and were considered as Group B. In Group A
      14(58.4%) at 1st week, 2(8.4%) at 1st month, 10(41.8%) at 3rd month and 5(21.0%)
      at 6th month developed burning sensation. On the other hand the values were
      18(75.0%), 22(91.6%), 14(58.2%) and 2(8.4%) at 1stweek, 1st month, 3rd month, and
      6th month respectively. Chi-square test was done for statistical analysis and p
      value was <0.05. So, results were statistically significant.

PMID- 29459595
TI  - Distribution, Management Difficulty and Outcome of Branchial Anomalies.
AB  - Branchial arch anomalies are one of the most common congenital anomalies of the
      neck. Developmental anomalies of the branchial apparatus account for 17% of all
      pediatric cervical masses. This study aimed to focus on proper diagnosis of
      branchial anomaly and describe occurrence, presentation, management and outcome
      of usual and unusual types. This ten-year prospective observational study was
      conducted from November 2005 to November 2015 including 2-year postoperative
      follow-up of the patients in Department of ENT, Bangabandhu Sheikh Mujib Medical
      University (BSMMU), Dhaka, Bangladesh. Total 89 patients were enrolled for this
      study. Information was recorded on Clinical examination, relevant investigation,
      Per-operative findings and Histo-pathological findings. After receiving Histo
      pathological findings 61 cases were proved as branchial arch anomalies.
      Ultrasonography and Histopathology was done for every patient. Fistulogram and
      sinogram was done for patient of fistula and sinus respectively. CT scan was
      needed for 9 patients, MRI for 3 patients and 12 patient undergone FNAC. Outcomes
      of those patients were described in terms of Hospital stay, Complications and
      Follow up studies. Data analysis was done by Standard Statistical
      Method.Presentation of a number of participant's mimics Branchial arch anomalies;
      4.91% was syndromal. Second branchial arch anomalies were the highest. Management
      was exclusively surgical. Recurrence rate was about 6.56%. Surgery is the tool
      for diagnosis, treatment, preventing complications, avoiding carcinoma for
      branchial arch anomalies.

PMID- 29459596
TI  - Irritable Bowel Syndrome: Prevalence and Dietary Factors in the Sylhet District
      of Bangladesh.
AB  - Irritable bowel syndrome (IBS) is a common functional bowel disorder. Along with
      other factors diet plays an important role in the causation of IBS. This
      population-based study was done to find out the prevalence of IBS and to find out
      the dietary factors associated with IBS from August 2011 to December 2011 in
      Sylhet district of Bangladesh. Nineteen hundred apparently healthy subjects
      selected by cluster sampling methods were interviewed by a validated bowel
      disease questionnaire. Dietary history of the subjects was also taken. Irritable
      bowel syndrome was diagnosed according to Rome III criteria. The prevalence of
      IBS was found 14.2% (n=269, M=15%, F=13.4%, p=0.365). Mean age of the IBS
      patients were higher than the study population (41.35 years vs. 34.74 years,
      p=0.000). Irritable bowel syndrome was found more in low education group (16.3%)
      with lower socioeconomic status (16.5%) and in single person (16.7%). IBSD was
      the most prevalent subtype (48.7%), IBSM was the next common subtype. Abdominal
      pain relieved by defecation (81%) and abdominal pain associated with loose stools
      (81%) were the two commonest symptoms. Age (OR 1.023, p=0.000), less intake of
      meat (OR 2.281, p=0.000) and pulses (OR 1.648, p=0.001) and more intake of tea
      (OR 1.524, p=0.009) and spices (OR 0.452, p=0.000) were found as independent
      predictor of IBS. Irritable bowel syndrome is a common disorder in our community.
      IBSD is the most prevalent subtype. Less intake of meat, pulses and more intakes
      of tea and spices are important associated factors for IBS.

PMID- 29459597
TI  - Prevalence of Metallo-beta-lactamase Producing Non-fermentative Pseudomonas
      Species from Clinical Isolates in Dhaka, Bangladesh.
AB  - Antimicrobial drug resistance, a global concern, has been increasing
      unpredictably in microorganism causing human infections specially among Gram
      negative non-fermenting Pseudomonas spp. Carbapenems, a beta lactam antibiotics,
      are the most potent and effective drug usually kept reserved for treating the
      multi-drug resistant Psedomonas spp and other infections caused by organisms
      producing Extended Spectrum Beta Lactamase (ESBL) and AmpC. Clinical utility of
      carbapenem will reduce when resistant bacteria evolve due to production of
      carbapenem hydrolyzing Metallo-beta-lactamase (MBL) which confers high-level
      resistance to all beta-lactam antibiotics except aztreonam. The various reports
      on the prevalence of MBLs are available from many countries but few from
      Bangladesh. We investigated the prevalence of MBL production in these
      Pseudomonads obtained from clinical sources in an uraban setting in Dhaka,
      Bangladesh. A total of 29,136 specimens were processed for culture from January
      2011 and December 2015 from non duplicated patients attending diagnostic unit of
      icddr,b from different settings of Bangladesh. The specimens included urine
      14,323; blood 11,378; other body fluid 2,487; sputum 535 and tracheal aspirate
      413. All specimens were processed for culture following standard bacteriological
      methods and the Pseudomonas spp were identified following defined standard
      biochemical procedures. Metallo-beta-lactamase (MBL) was determined by EDTA disk
      synergy (EDS) test. Antimicrobial susceptibility test was performed by disk
      diffusion method and susceptibility pattern was interpreted and reported
      following Clinical Laboratory Standard Institute (CLSI) guideline. From 29,136
      specimens a total of 2,340(8%) were isolated and identified as Pseudomonas spp.
      Of the identified Pseudomonas spp, 238(57.6%) were from tracheal aspirate,
      216(40.4%) from sputum, 902(36.7%) from other body fluids, 463(4.1%) from blood
      and 521(3.6%) from urine samples. From 2,340 Pseudomonas spp, by selective
      sampling, imipenem-meropenem resistant and intermediate susceptible 100 strains
      were tested for MBL production and 92 were found positive. Tracheal aspirate
      showed 38%, other body fluids 30%, Urine 17%, sputum 4% and blood 3% MBL
      production respectively. Irrespective of the sources of specimens, Pseudomonas
      spp showed 71% resistance to cefixime, 70% to ceftriaxone, 64% to gentamicin, 56%
      to piperecillin+tazobactam, 50% to ciprofloxacin, 49% to amikacin, 46% to
      netilmicin, 45% to ceftazidime, 30% to meropenem, 26% to imipenem and 19% to
      polymyxin B. As multi-drug resistant Pseudomonas showed high level of (92%) MBL
      production, so MBL detection testing facility may be a useful battery to
      determine MDR producing Pseudomonas from clinical isolates.

PMID- 29459598
TI  - Abandonment and Outcome of Childhood Acute Myeloid Leukemia in A Tertiary Level
      Hospital.
AB  - Acute leukemias are the most common child hood malignancy, of which acute myeloid
      leukemia (AML) are 15 to 20%. Abandonment is one of the most important causes of
      treatment failure in AML in developing countries. Lost to follow-up is also a big
      problem in low income countries. Many patients stop therapy soon after diagnosis
      due to cost, distance and ignorance. To determine the abandonment, outcome and
      treatment related mortality (TRM) and morbidity among children with AML. This
      prospective observational study was conducted in the Department of Pediatric
      hematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU),
      Dhaka from February 2013 to January 2014. Fifty (50) patients of AML visited to
      out patient department (OPD) of Pediatric hematology and Oncology. Among them
      11(22%) patients refuse treatment from outdoor. Thirty nine (78%) patients of AML
      were selected as per inclusion and exclusion criteria. After proper evaluation
      and clinical examination of these patients, CBC and Bone marrow examination was
      done for confirmation of diagnosis. A total of 39 patients were recruited in this
      study. Seventeen (43.6%) patients were male and 22(56.4%) were female. Mean+/-SD
      of age was 7.80+/-4.42 years and range was 1 year to 18 years. Out of 39
      patients, 18(46.1%) patients were abandoned, 15(38.4%) expire, relapse 2(5.2%) &
      alive 4(10.3%). High abandonment (46.1%) and treatment related toxic death
      (38.4%) has compromised the outcome of acute myeloid leukemia. However AML can be
      treated with better outcome if improved the supportive care, reduce toxic death,
      refusal or abandonment.

PMID- 29459599
TI  - Erythrocyte Glucose-6-Phosphate Dehydrogenase Level in Type 2 Diabetes Male.
AB  - The patient with diabetes mellitus (DM) and its complication is increasing in our
      country and all over the world. There is also significant increase in the
      prevalence of erythrocyte glucose-6-phosphate dehydrogenase (eG6PD) deficiency in
      the men with longer duration of diabetes mellitus. To assess the eG6PD in type 2
      diabetes male subjects to observe their enzyme status. This cross-sectional study
      was conducted in the Department of Physiology, Dhaka Medical College, Dhaka,
      Bangladesh from January 2011 to December 2011. Sixty male subjects with type 2
      diabetes mellitus were selected with the age ranging from 40 to 60 years. Out of
      diabetic subjects, 30 (thirty) were with controlled (B1) and other 30 (thirty)
      with uncontrolled (B2) type 2 diabetes mellitus were selected from Outpatient
      Department of BIRDEM Hospital by random basis. And 30 age-matched, healthy non
      diabetic male subjects were considered as control group for comparison.
      Erythrocyte G6PD level was measured by spectrophotometric method. Fasting Blood
      Glucose (FBG), HbA1c were measured by standard laboratory techniques in the
      laboratory of BIRDEM and Armed Forces Institute of Pathology (AFIP), Dhaka
      Cantonment, Dhaka. For statistical analysis unpaired Student's 't' test was
      performed. The result was expressed as Mean+/-SD among the groups. In this study,
      eG6PD level was significantly lower in both the study groups. This study
      concludes that eG6PD level decreases in male with diabetes mellitus.

PMID- 29459600
TI  - Comparative Study of Patellar Tendon Graft versus Hamstrings Graft for Anterior
      Cruciate Ligament Reconstruction.
AB  - Graft selection for primary anterior cruciate ligament reconstruction is very
      important part of knee stability. The purpose of this Qasi experimental study was
      to compare the clinical outcomes after ACL reconstruction using either a BPTB
      graft or a four-strand hamstrings graft and conducted from January 2012 to
      December 2013. Patients presented with a symptomatic unilateral ACL rupture who
      were underwent ACL reconstruction by using either BPTB or Hamstrings graft, IPD
      of Department of Orthopedics at Bangabandhu Sheikh Mujib Medical University
      (BSMMU), Dhaka as well as in a private hospital in Dhaka, Bangladesh were
      selected as study population. Patients were divided into Group A who were treated
      with the patellar tendon bone graft and Group B patients who were received
      hamstrings tendon graft. All surgery was performed by the same surgeon and the
      both procedures were arthroscopically assisted. Operation was performed at least
      three (03) weeks after initial trauma. All patients were assessed by independent
      examiner before surgery, at 6 months, 12 months and then annually by clinically.
      A total number of 70 patients were recruited for this study. The mean age with SD
      of Group A and Group B were 27.31+/-10.91 and 26.97+/-10.10 years respectively
      (p=0.892). Tegner scores were measured preoperatively and post-operatively. The
      score were 2.2+/-1.1 and 2.1+/-1.0 in preoperatively (p=0.817). In post
      operatively the mean score were 6.0+/-1.7 and 5.8+/-1.5 in Group A and Group B
      respectively (p=0.508). Regarding outcome of the operation excellent was 18(51%)
      cases in both Group A and Group B, good was 15 (43%) and 16(46%) cases in Group A
      and Group B respectively (p=0.793). In conclusion there was no significant
      difference between the two groups of the ACL reconstructions cases.

PMID- 29459601
TI  - Age Related Variation in the Number of Endometrial Gland in Bangladeshi Cadaver.
AB  - This cross-sectional descriptive study was done to see the variation in the
      number of endometrial gland in Bangladeshi cadaver in different age groups to
      find out the anatomical variation and to compare it with other study findings.
      For this purpose 30 post mortem specimens containing female genital organs
      particularly uterus were collected by purposive sampling technique from cadavers
      of different age groups. All the collected specimens were fixed in 10% formalin
      solution. This study was carried out in the department of Anatomy, Mymensingh
      Medical College from July 2006 to June 2007. After dissection of specimen,
      microscopic study was done to count the number of the endometrial glands. Mean+/
      SD numbers of gland per square mm area were 5.88+/-1.56, 14.75+/-6.90, and 7.35+/
      1.79 in age Group A (2-12 years), B (13-45 years) & C (46-80 years) respectively.
      Highest number of gland was seen in Group B (5.66 to 22.48 per sq mm) & lowest
      number of gland was seen in Group A (3.30 to 9.95 per sq mm). The present study
      findings were compared with that of the references.

PMID- 29459602
TI  - Pattern and Extent of Tricuspid Valve Involvement in Chronic Rheumatic Heart
      Disease.
AB  - Rheumatic heart disease causes a significant number of morbidity and mortality in
      Bangladesh. Although the mitral and the aortic valve are the two most involved
      valves in rheumatic heart disease, the tricuspid valve disease is not uncommon
      secondary to, or in association with, mitral or aortic valve disease, but
      receives less attention as compared to the primary left-sided valve disease.
      Appropriate treatment of the tricuspid valve disease may improve long-term
      functional outcome. But the pattern and extent of the tricuspid valve involvement
      was not studied recently. This study was carried out to observe the pattern and
      extent of tricuspid valve involvement in Rheumatic Heart Disease patients. This
      observational analytical study was undertaken in the department of Cardiology,
      Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from December 2010
      to September 2011. Considering all ethical issues, data were collected from 173
      subjects who underwent Echocardiography for their Chronic Rheumatic heart
      disease. Pattern of tricuspid valve involvement was observed by using
      Transthoracic Echocardiography by 2D, M mode and Doppler assessment. One hundred
      seventy three (173) patients with Rheumatic Heart disease was studied, out of
      these, 36 patients had evidence of tricuspid valve involvement based on
      echocardiographic findings. Fifteen (15) patients had Tricuspid stenosis and 36
      patients had Tricuspid Regurgitation in the patients with TV involvement. All the
      patients with TV involvement had thickened leaflets. Doming, restriction of
      motion and calcification were present in different proportions. From this study,
      it can be concluded that organic tricuspid valve involvement in RHD is not
      uncommon in our country.

PMID- 29459603
TI  - Study of Angiographic Relationship between Peripheral Arterial Diseases with the
      Involvement of Specific Coronary Artery Lesion.
AB  - The purpose of this study was to investigate magnitude, pattern and involvement
      of previously unheralded coronary artery disease in patients suffering from
      clinically significant peripheral artery disease of lower limbs. This cross
      sectional study was carried out in National Institute of Cardiovascular Diseases,
      Dhaka, Bangladesh from January 2014 to February 2015. Total 58 patients with
      clinically diagnosed peripheral arterial disease of lower limb undergoing
      angiographic evaluation. Selective CAG in addition to peripheral arteriography
      was performed in all the study population as per ACC/AHA guidelines for CAG
      (class IIa recommendation).In this study, it was documented that the proportion
      of coronary arterial disease was highest in LAD (63.9%) followed by LCX (55.6%),
      RCA (52.8%), and lowest LM (11.1%) in lesion with aorto-iliac segment. But the
      proportion of coronary arterial disease was highest in LCX (41.9%) followed by
      LAD (38.7%), RCA (35.5%), and lowest LM (12.9%) in lesion with femero-popliteal
      blood vessels. Similarly, the proportion of coronary arterial disease was highest
      in LCX (36.4%) followed by RCA (27.3%) and equal percentage in LAD and lowest in
      LM (9.1%) in tibioperoneal segment. Patients of peripheral arterial disease (PAD)
      having no symptoms of coronary artery disease (CAD) are more likely to have
      severe coronary artery involvement. Coronary angiogram should be done in patient
      with PAD to detect previously undetected CAD and pattern of PAD reflects the
      severity and involvement of coronary arteries.

PMID- 29459604
TI  - Immediate Outcome of Preterm Neonates with Respiratory Distress Syndrome Required
      Mechanical Ventilation.
AB  - Since its inception, the neonatal mechanical ventilator has been considered an
      essential tool for managing preterm neonates with Respiratory Distress Syndrome
      (RDS) and is still regarded as an integral component in the neonatal respiratory
      care continuum. Mechanical ventilation of newborn has been practiced for several
      years with several advances made in the way. This clinical intervention study was
      done to analyze immediate outcome of preterm neonates with RDS required
      mechanical ventilation and conducted on preterm neonates with RDS required
      mechanical ventilation from July 2014 to June 2015. Total of 31 preterm neonates
      with RDS were mechanically ventilated during the study period, of which 77.42%
      (N=24) survived. The survival rate was highest among 30- <34 weeks (100%)
      gestational age (GA) group and lowest in 27- <30 weeks (56%) GA, (p=0.0036). The
      neonates with Birth Weight (BW) 1500gm -1800gm were higher rate of recovery which
      was 100% and gradually declined in 1000-1499gm (93.75%) and 800-999gm (33.33%) BW
      groups (p=0.00083). In this study most of the neonates were male (61.29%) but
      recovery rate was relatively better among baby girls (83.33%) than baby boys
      (73.68%) (p=0.53). RDS with surfactant therapy was better outcome than non
      surfactant group & survival of neonates who got surfactant were 93.33% & non
      surfactant neonates were 62.50%, (p=0.040). Majority (71.43%) of RDS with
      surfactant therapy recovered earlier <7 days than non surfactant therapy neonates
      (30.00%) and most of non surfactant neonates (70.00%) required prolonged
      ventilator support >7days (p=0.045). During the period of ventilation a total
      17(54.84%) neonates developed different complications, of which ventilator
      associated pneumonia was (16.13%), sepsis (16.13%), pneumothorax (9.68%),
      pulmonary hemorrhage (6.45%) and intraventricular hemorrhage (6.45%) and among
      them 10 neonates recovered. No complications encountered in 14(45.16%) neonates,
      all of them survived, (p=0.0064). All (N=31) preterm neonates were candidate for
      surfactant therapy but only 15 neonates got surfactant therapy, remaining (N=16)
      did not get for their financial issue. As mechanical ventilation with surfactant
      therapy reduces the neonatal mortality; hence, facilities for neonatal
      ventilation and cost effective surfactant therapy should be included in the
      regional and central hospitals providing intensive care for neonates.

PMID- 29459605
TI  - Evaluation of the Results of Ilizarov Ring Fixation in Schatzker Type VI Tibial
      Plateau Fracture.
AB  - High-energy tibial plateau fractures associated with severe soft tissue injury
      are difficult to manage. The risk of wound complications following open reduction
      and internal fixation is notably high owing to extensive soft tissue dissection.
      Alternatively, application of Ilizarov ring fixator minimizes soft tissue
      dissection and provides adequate fracture stabilization to allow early range of
      motion and correction of any mal-alignment. With this technique, soft tissue
      complications particularly surgical site infections are expected to be
      significantly reduced. This prospective interventional study was conducted from
      January 2012 to December 2013 at National Institute of Traumatology and
      Orthopaedic Rehabilitation (NITOR), Dhaka, Bangladesh. Ten patients with tibial
      plateau fracture Schatzker type VI were treated with Ilizarov ring fixator.
      Patients were visited routinely and final outcome evaluation done according to
      Rasmussen's functional grading system and radiological evaluation. Among the 10
      patients of type-VI Schatzker tibial plateau fractures, the mean range of knee
      movement was 95.5 degrees . The mean Rasmussen functional score was 23.6 (range,
      16-28): excellent in 3 patients, good in 5 and fair in 2.

PMID- 29459606
TI  - Clinical and Neuro-radiological Presentation of Tuberous Sclerosis Complex in
      Tertiary Care Centre.
AB  - Tuberous sclerosis complex (TSC) is a common neurocutaneous disorder
      characterized by hamartomatous changes in the lungs, brain, kidneys, skin, heart,
      and other organs. This retrospective study was done to see the clinical
      presentation and neuro imaging pattern of TSC in a tertiary care centre of
      Bangladesh and was conducted at Pediatric Neurology Unit of Bangabandhu Sheikh
      Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2013 to December
      2013. Among total 10 patients male-female ratio was 3:2. Commonest age group was
      1-5 year in 50%. Common cutaneous abnormality was facial angiofibroma in 100%.
      Commonest neurological presentation was epilepsy in100%, ASD in 20% patient.
      Common renal manifestation was multicystic kidney disease (20%). CT/MRI findings
      were periventricular calcifications in 70% patients. In this study facial
      angiofibroma is the most common skin manifestation and epilepsy is the common
      neurological presentationandperiventricular calcification is the most common
      neuro-radiological findings in tuberous sclerosis complex.

PMID- 29459607
TI  - Forgotten, Encrusted Ureteral Stents: Removal - Multimodal Endourologic Approach.
AB  - Ureteral stent placement is a common procedure in urologic practice. Forgotten,
      encrusted D/J stents represent a difficult problem for urologists. The major
      complications are infection, impaired renal function, migration, encrustation,
      stone formation and multiple fragmentation of stent. A consensus on the best
      therapeutic approach is still lacking. Here we present our experience with
      endoscopic management of this challenging problem and discuss the multimodal
      endourologic approaches for treating forgotten, encrusted ureteral stents. In
      this prospective observational study 29 patients (17 males and 12 females), age
      ranges from 19 to 57 years with 35 (23 unilateral and 6 bilateral) encrusted
      ureteral stents, indwelling for 5 to 78 months were treated in the Department of
      Urology, Dhaka Medical College Hospital (DMCH), Dhaka, Bangladesh from January
      2011 to December 2015. All patients were evaluated by urine culture and
      sensitivity, renal function. Stent encrustation and the associated stone burden
      were estimated by plain radiograph. Treatment decisions were made based on the
      clinical presentation, degree of encrustation, stone burden and image findings.
      Patients were followed up to 06 months. The main indications for stenting were
      pyelolithotomy, ureterolithotomy, ureteroneocystostomy, URS and pyeloplasty. In
      kidney, mild encrustation was common (48.3%) moderate encrustation (27.6%) was
      less common; where as in ureter and urinary bladder, moderate encrustation was
      common (72.4% and 44.8%). Over three-quarters 22(75.9%) of the patients underwent
      extracorporeal shockwave lithotripsy (ESWL) and 10(34.5%) percuteneousnephrostomy
      preoperatively. Retrograde ureteroscopy with intracorporeal lithotripsy (URS &
      ICPL) was done in 29 cases and cystolitholapaxy (CLL) in 16(55%) cases.
      Cystolithotomy & PCNL was rarely done. The mean number of procedures was 2.8
      (range: 1-7). Using these multimodal approaches, all stents and associated stones
      were eventually removed with minor complications. Nine patients developed
      haematuria, 5 urosepsis and 4 both haematuria & urosepsis. Multimodal
      endourologic approaches can safely remove forgotten, encrusted D/J stents, if
      treatment is tailored to the volume of encrustation and associated stone. Imaging
      evaluation and documentation of negative urine culture are imperative prior to
      any attempt to remove the stent.

PMID- 29459608
TI  - Distribution Pattern and Outcome of the Patients in the Intensive Care Unit of
      Bangabandhu Sheikh Mujib Medical University: A Short Term Analysis.
AB  - The aim of the study was to describe the characteristics of patients admitted to
      intensive care unit and their outcome in Bangabandhu Sheikh Mujib Medical
      University, Bangladesh. This retrospective, descriptive study was conducted in
      the intensive care unit of Bangabandhu Sheikh Mujib Medical University (BSMMU)
      from January 2016 to June 2016. Data was retrieved from hospital records of all
      admitted patients regarding age, gender, admission source, reason for admission,
      length of ICU stay, requirement of mechanical ventilation, number of organ
      failure and their outcome. During this study period, the total number of patients
      admitted was 225; most of them were males (148, 65.7%). Among the 225 patients,
      the highest number of admission was comprised of intracranial haemorrhage
      (22.6%), followed by sepsis (12.4%), acute respiratory distress syndrome (10.2%),
      acute renal failure (9.3%) malignancy (8.8%) and ischemic stroke (8.0%). Mean age
      of the patient was 54+/-18 years and mean length of ICU stay was 6.8+/-3 days.
      Out of 225 patients, 87 expired (38.6%). Majority of the patients required
      mechanical ventilation (69.3%) and had multi organ failure (59.8%). Most of the
      expiries were due to intracranial haemorrhage (24.1%); followed by acute
      respiratory distress syndrome (12.6%), malignancy (12.6%) and sepsis (11.4%).
      Elderly age (>65 years), requirement of mechanical ventilation and multiorgan
      failure had significant relationship (p<0.05) with overall ICU mortality.
      Intracranial haemorrhage, sepsis, acute respiratory distress syndrome were the
      main reasons for admissions in ICU, while mortality was highest for intracranial
      haemorrhage. Developing a well equipped neurological ICU with adequately trained
      staff will help to improve the outcome of patients.

PMID- 29459609
TI  - Psychiatric Morbidities among Male Juvenile Offenders: A Cross Sectional
      Comparison in Bangladesh.
AB  - Inmates of Juvenile Developmental Centers are the special group of youth
      population who are in conflict with law and are vulnerable to psychiatric
      disorders. It was aimed to see the variation of prevalence and type of
      psychiatric disorders in institutionalized male juvenile offenders and non
      offenders of same age, sex and socioeconomic group in the community. The
      association of mental disorders was examined in 138 male inmates of Juvenile
      Development Centers and 138 randomly selected comparison subjects in community.
      One stage-structured assessment of psychopathology was carried out by using a
      structured and valid Bangla version of the Development and Well-Being Assessment
      (DAWBA). Psychiatric diagnosis was established after scoring from DAWBA that is
      actually corresponds to diagnosis of ICD-10 for research. It was revealed that,
      of those who were in conflict with law, 57.2% had mental disorder, whereas 9.4%
      of non-offenders had psychiatric disorder. Among the offenders with psychiatric
      disorders, most of them (16.7%) suffered from Conduct Disorder (CD), followed by
      Major Depressive Disorder (MDD). On the other hand, among the non-offenders with
      psychiatric disorder 2.2% suffered from CD. Study revealed that psychiatric
      disorders are more prevalent among the male juvenile offenders with comparison to
      non-offenders. Broad-based multi centered and cross cultural replication study
      can generalize the findings.

PMID- 29459610
TI  - Admission Troponin I and Post Thrombolytic ST-Segment Resolution in Prediction of
      Early Risk Stratification in ST- Elevation Myocardial Infarction.
AB  - The prognostic value of admission troponin I (tnI) levels and the resolution of
      the ST-segment elevation in ST-elevation myocardial infarction (STEMI) is well
      established. However, the combination of these two early available markers for
      predicting the risk of early mortality has not been evaluated yet. This
      prospective analytical study conducted in the department of Cardiology, Sir
      Salimullah Medical College and Mitford Hospital, Dhaka and NICVD, Dhaka,
      Bangladesh from March 2004 to February 2005. We have evaluated 80 patients with
      streptokinase treated STEMI who had both admission troponin I and ST-monitoring.
      We used a prospectively defined cut-off value of troponin I of 0.1ng/ml. For ST
      segment resolution, a cut-off of 50% measured after 90 minutes was used. Both a
      troponin I >0.1ng/ml and ST segment resolution <50% was related to higher early
      mortality; 16.7% vs. 14.3% (p<0.001) and 57.1% vs. 1.7% (p<0.001) respectively.
      In a multivariate analysis ST-segment resolution was and troponin I showed a
      strong trend to be independently related to early mortality. The combination of
      both further improved risk stratification. The early mortality in the group with
      elevation of troponin I and without ST-segment resolution compared to the group
      without troponin I elevation and with ST-segment resolution was 55.6% vs. 0%.
      Both troponin I on admission and ST-segment resolution after 90 minutes are
      strong predictors of early mortality. The combination of both gives additive
      early information about prognosis and further improves risk stratification.

PMID- 29459611
TI  - Non-convulsive Status Epilepticus in Children: Clinical Profile, EEG
      Characteristics and Treatment.
AB  - Non-convulsive status epilepticus (NCSE) is a term used to denote a range of
      conditions in which electrographic seizure activity is prolonged and results in
      non-convulsive clinical symptoms. This study was done to describe the clinical
      spectrum, EEG findings and to evaluate the efficacy of different therapeutic
      agents in children with NCSE in 33 patients from January 2011 to December 2015
      period. All patients had EEG before and after treatment. Age range was 6 months
      to 14 year, 25 were male. Regarding development status, 48% had developmental
      delay, 21% had normal development, 9% had regression and 21% had both
      developmental delay and regression. Twenty nine cases were previously diagnosed
      as epilepsy. EEG diagnosis was as follows: Generalized NCSE 23(69%), focal
      9(27%), unknown 1(3%). Eighteen patients were treated with Midazolam drip out of
      which 1 patient had complete remission in EEG, 6 had >80% remission, 5 had >50%
      remission and 5 patients had minimal or no response. Thirteen patients were
      treated with methyl prednisolone bolus out of which 2 patients had complete
      remission, 4 patients had >80% remission while 4 patients had >50% remission and
      3 patients showed no response. NCSE may present with various clinical feature
      without any convulsion. Midazolam, methyl prednisolone and oral drugs are equally
      effective for treatment of NCSE. However, further randomized controlled study is
      needed to chalk out management of NCSE.

PMID- 29459612
TI  - Review of Uterine Sling after Five Years of Operation in a 40 Years Lady.
AB  - Uterine sling is a operation, done with own rectus sleeve to correct the uterine
      descend. If necessary correction of cystocele and/or rectocele and or perineal
      tear done on the same sitting. After 5 years of such operation abdomen of Mrs. X
      was opened due to ovarian cyst in Nirapad Hospital, Shantinagar, Dhaka,
      Bangladesh on August 2016. Uterus was found in normal position and size. Rectus
      sleeves were found attached with the uterus where it was anchored. Omentum was
      attached over the rectus sleeves and sealed the weak points at both lateral ends
      of the rectus sleeves through which the sleeves were taken to the abdominal
      cavity. Omentum was also attached to the posterior leaf of the broad ligaments
      where the sleeves were sutured to minimize the dead spaces. During this 5 years
      period the patient felt no discomfort or pain due to the sling or experiences any
      further descend of the uterus.

PMID- 29459613
TI  - Complete Annular Pancreas with Concurrent Entero-Pancreatico-Biliary Symptoms in
      Adult: A Case Report.
AB  - Complete Annular pancreas (AP) is a rare congenital anomaly, often presented and
      operated at the early age of life. Adult presentation group usually presents with
      either biliary or duodenal or pancreatic symptoms. We report a case of 43 years
      old female presenting with concurrent enteric, biliary and pancreatic symptoms
      admitted on April 2016 in Hepatobiliary and Pancreatic Surgery Department of
      BSMMU, Dhaka, Bangladesh. A complete type of annular pancreas with partial
      duodenal stenosis and dilated common bile duct was observed during laparotomy. We
      performed gastrojejunostomy as well as hepaticojejunostomy (Roux-en-Y
      anastomosis). Patient was discharged in a good symptom free condition. Complete
      Annular Pancreas can present at any age, with any one or all of the biliary,
      pancreatic or duodenal symptoms. Surgery is the treatment of choice and has a
      good outcome.

PMID- 29459614
TI  - A Case of Severe Coarctation of Aorta Associated With Bicuspid Aortic Valve
      Managed Surgically.
AB  - Coarctation of the aorta is a congenital cardiac malformation that can go
      undiagnosed until old age with only hypertension as a marker of its presence
      because clinical signs can be subtle and overlooked if a complete physical exam
      is not performed. Long-term survival is exceptional in patients with untreated
      aortic coarctation. In this case report, we present a late diagnosis of aortic
      coarctation in a 45-year-old male. Our patient was relatively asymptomatic until
      he presented with exertional dyspnea and fatigue in his fourth decade of life in
      Bangabandhu Sheikh Mujib Medical University (BSMMU), on the month of August,
      2016. The patient was managed by surgery of aorta. After the 6 months follow-up
      visit, the patient was in good clinical condition.

PMID- 29459615
TI  - Double Heterozygous For Haemoglobin S and Haemoglobin E.
AB  - Here we present a Bangladeshi family where out of four family members two (mother
      and son) inherited both haemoglobin (HbS) S and haemoglobin (HbE) E gene
      confirming the diagnosis of double heterozygous state for HbS and HbE, presented
      in the Armed Forces Institute of Pathology (AFIP), Dhaka Cantonment, Dhaka,
      Bangladesh on the month of July 2016. Among other two members, one (daughter)
      inherited HbS and other (father) HbE. Double heterozygous state for HbS and HbE
      is a rare condition in this subcontinent especially in Bangladesh. HbS is rare
      but HbE is prevalent in Bangladesh. Co-inheritance of both HbS and HbE is
      therefore uncommon in this country in comparison to HbE/beta - thalassaemia.
      Though the double heterozygous state for HbS and HbE is rare and the patients are
      usually asymptomatic but their documentation is important for genetic counseling
      and to determine the reproductive risk of the family.

PMID- 29459616
TI  - Gliomatosis Cerebri: A Rare Brain Tumor.
AB  - Gliomatosis Cerebri is a rare brain tumor. There is diversity of presentation in
      cases due to the nature of its diffuse involvement. Very recently, on February
      2016 in the department of Paediatric Neurology, Bangabandhu Sheikh Mujib Medical
      University (BSMMU), Dhaka, Bangladesh we encountered a 10 years old boy who
      initially mimicked as tuberculoma of brain but later on diagnosed as Gliomatosis
      Cerebri on the basis of brain MRI and brain biopsy. Prognosis is always very
      gloomy regardless of the treatment strategy adopted. The boy died within one year
      after confirmation of diagnosis even after getting adequate medical management
      and radiation therapy.

PMID- 29459617
TI  - NGAL (Neutrophil Gelatinase-associated Lipocalin) is an Early Predictor of Acute
      Kidney Injury after Cardiac Surgery and Variation of NGAL Values in Homogenous
      Study Subject.
AB  - Isolated CABG (coronary artery bypass grafting) has the lowest incidence of AKI
      (Acute Kidney Injury), followed by valvular surgery and then, combined CABG with
      valvular surgery. Due to the difference in baseline characteristics and in
      surgery type, the range of incidence is between 8.9 and 39% based on RIFLE (Risk
      Injury failure loss end stage kidney disease) or AKIN (Acute Kidney Injury
      Network) criteria. The advent of novel biomarkers of kidney injury has opened a
      new era of early detection and prognosis prediction for AKI. NGAL is a small
      molecule of 178 amino acids that belongs to the super family of lipocalins, which
      are proteins specialized in binding and transporting small hydrophobic molecules.
      The expression of NGAL raises 1000 fold in humans and rodents in response to
      renal tubular injury and it appears so rapidly in the urine and serum that it is
      useful as an early biomarker of renal failure. The role of plasma NGAL to
      classify AKI severity and predict the need for RRT (renal replacement therapy)
      after cardiac surgery has been suggested. Although study subjects were more or
      less from same cohort (All undergone cardiac surgery), previous studies showed
      that NGAL raised differently in different proportion. NGAL as an early AKI marker
      has successfully passed through the pre-clinical, assay development and initial
      clinical testing stages. It is badly need to enter in a consensus about the
      cutoff value of NGAL which should help the physician about leveling a case as AKI
      or non AKI and their consequence management.

PMID- 29459618
TI  - Irritable Bowel Syndrome: Is it Rare in Children?
AB  - Irritable bowel syndrome (IBS) is one of the most common and best studied
      disorders among the group of functional gastrointestinal disorders. It is a
      functional bowel disorder in which abdominal pain or discomfort is associated
      with defecation or a change in bowel habit. Visceral hypersensitivity and
      increased GIT motility are the main patho-physiological mechanism for developing
      IBS. IBS present with diarrhea and constipation or both. Investigation is least
      needed for diagnosis of IBS rather done to exclude differential diagnosis.
      Diagnosis is done on the basis of Rome-III criteria. Proper counseling, dietary
      management, anti-spasmotic and antidepressant are the mainstay of treatment.

PMID- 29459619
TI  - Quality and learning aspects of the first 9000 spirometries of the LifeGene
      study.
AB  - Spirometry requires the patient to cooperate and do the manoeuvre 'right' for
      reliable results. Algorithms to assess test quality as well as educational
      recommendations for personnel are defined in guidelines. We compared the quality
      of forced spirometry tests performed by spirometry technicians with little or no
      previous experience of spirometry using spirometry systems with different modes
      of feedback. In both cases, the spirometry technician received general feedback
      on the screen based on ATS/ERS guidelines, such as 'exhale faster' and 'exhale
      longer'. The major difference was whether quality grading system of the complete
      session was available simultaneously on screen, or in the printed report
      afterwards. Two parts of the same population-based study (LifeGene), the pilot
      (LG1) and the first part (LG2) of the subsequent study, were compared
      retrospectively. In LG1 (on-screen grading) approved examination quality was
      achieved for 88% of the 10 first subjects for each spirometry technician compared
      to 70% in LG2 (printed grading afterwards). The corresponding values after 40
      subjects was 94 % in LG1, compared to 73% in LG2, and after the first ten
      subjects there was no apparent quality improvement in either LG1 or LG2. The
      quality for LG1 is among the highest reported in the literature even though the
      spirometry technician were relatively inexperienced. We conclude that on-screen
      grading in addition to general technical quality feedback is powerful in
      enhancing the spirometry test session quality.

PMID- 29459620
TI  - New insights into the cellular responses to iron nanoparticles in Capsicum
      annuum.
AB  - In this study, the anatomical and ultrastructural responses of Capsicum annuum to
      iron nanoparticles (Fe NPs) were determined. The results showed that the bio
      effects of Fe NPs on plants could be positive or negative, depending on the
      additive concentrations. Low concentrations of Fe NPs were found to promote plant
      growth. Light and electron microscope analyses showed that the Fe NPs promoted
      plant growth by altering the leaf organization, and increasing the chloroplast
      number and grana stacking, as well as regulating the development of vascular
      bundles. Meanwhile, it was found that the Fe NPs could be absorbed in the roots,
      and then transported to the central cylinder in bio-available forms, where they
      were translocated and utilized by the leaves and stems. In contrast, high
      concentrations of Fe NPs appeared to be harmful to the plants, and the majority
      of Fe NPs were aggregated into cell walls and transported via the apoplastic
      pathway in the roots, which may potentially block the transfer of iron nutrients.
      Taken together, the aforementioned data showed that the rational use of Fe NPs
      could alleviate iron deficiency, and Fe NPs could be an ideal supply for Fe2+
      ions fertilizers in agriculture.

PMID- 29459621
TI  - Ultrafast quantum control of ionization dynamics in krypton.
AB  - Ultrafast spectroscopy with attosecond resolution has enabled the real time
      observation of ultrafast electron dynamics in atoms, molecules and solids. These
      experiments employ attosecond pulses or pulse trains and explore dynamical
      processes in a pump-probe scheme that is selectively sensitive to electronic
      state of matter via photoelectron or XUV absorption spectroscopy or that includes
      changes of the ionic state detected via photo-ion mass spectrometry. Here, we
      demonstrate how the implementation of combined photo-ion and absorption
      spectroscopy with attosecond resolution enables tracking the complex
      multidimensional excitation and decay cascade of an Auger auto-ionization process
      of a few femtoseconds in highly excited krypton. In tandem with theory, our study
      reveals the role of intermediate electronic states in the formation of multiply
      charged ions. Amplitude tuning of a dressing laser field addresses different
      groups of decay channels and allows exerting temporal and quantitative control
      over the ionization dynamics in rare gas atoms.

PMID- 29459622
TI  - Effects of predispersal insect seed predation on the early life history stages of
      a rare cold sand-desert legume.
AB  - Seed predation by insects is common in seeds of Fabaceae (legume) species with
      physical dormancy (PY). However, the consequences of insect seed predation on the
      life history of legumes with PY have been little studied. In the largest genus of
      seed plants, Astragalus (Fabaceae), only one study has tested the effects of
      insect predation on germination, and none has tested it directly on seedling
      survival. Thus, we tested the effects of insect predation on seed germination and
      seedling growth and survival of Astragalus lehmannianus, a central Asian sand
      desert endemic. Under laboratory conditions, seeds lightly predated in the
      natural habitat of this perennial legume germinated to a much higher percentage
      than intact seeds, and seedlings from predated and nonpredated seeds survived and
      grew about equally well. Further, in contrast to our prediction seedlings from
      predated seeds that germinated "out-of-season" under near-natural conditions in
      NW China survived over winter. The implication of our results is that individual
      plants from predated seeds that germinate early (in our case autumn) potentially
      have a fitness advantage over those from nonpredated seeds, which delay
      germination until spring of a subsequent year.

PMID- 29459623
TI  - Rapid emergence of independent "chromosomal lineages" in silvered-leaf monkey
      triggered by Y/autosome translocation.
AB  - Sex/autosome translocations are rare events. The only known example in
      catarrhines is in the silvered-leaf monkey. Here the Y chromosome was
      reciprocally translocated with chromosome 1. The rearrangement produced an
      X1X2Y1Y2 sex chromosome system. At least three chromosomal variants of the intact
      chromosome 1 are known to exist. We characterized in high resolution the
      translocation products (Y1 and Y2) and the polymorphic forms of the intact
      chromosome 1 with a panel of more than 150 human BAC clones. We showed that the
      translocation products were extremely rearranged, in contrast to the high level
      of marker order conservation of the other silvered-leaf monkey chromosomes.
      Surprisingly, each translocation product appeared to form independent "chromosome
      lineages"; each having a myriad of distinct rearrangements. We reconstructed the
      evolutionary history of the translocation products by comparing the homologous
      chromosomes of two other colobine species: the African mantled guereza and the
      Indian langur. The results showed a massive reuse of breakpoints: only 12, out of
      the 40 breaks occurred in domains never reused in other rearrangements, while,
      strikingly, some domains were used up to four times. Such frequent breakpoint
      reuse if proved to be a general phenomenon has profound implications for
      mechanisms of chromosome evolution.

PMID- 29459624
TI  - Background matching in the brown shrimp Crangon crangon: adaptive camouflage and
      behavioural-plasticity.
AB  - A combination of burrowing behaviour and very efficient background matching makes
      the brown shrimp Crangon crangon almost invisible to potential predators and
      prey. This raises questions on how shrimp succeed in concealing themselves in the
      heterogeneous and dynamic estuarine habitats they inhabit and what type of
      environmental variables and behavioural factors affect their colour change
      abilities. Using a series of behavioural experiments, we show that the brown
      shrimp is capable of repeated fast colour adaptations (20% change in dark pigment
      cover within one hour) and that its background matching ability is mainly
      influenced by illumination and sediment colour. Novel insights are provided on
      the occurrence of non-adaptive (possibly stress) responses to background changes
      after long-time exposure to a constant background colour or during unfavourable
      conditions for burying. Shrimp showed high levels of intra- and inter-individual
      variation, demonstrating a complex balance between behavioural-plasticity and
      environmental adaptation. As such, the study of crustacean colour changes
      represents a valuable opportunity to investigate colour adaptations in dynamic
      habitats and can help us to identify the mayor environmental and behavioural
      factors influencing the evolution of animal background matching.

PMID- 29459625
TI  - Molecular subtypes of Alzheimer's disease.
AB  - Protein misfolding and aggregation is a central feature of several
      neurodegenerative disorders including Alzheimer's disease (AD), in which
      assemblies of amyloid beta (Abeta) peptides accumulate in the brain in the form
      of parenchymal and/or vascular amyloid. A widely accepted concept is that AD is
      characterized by distinct clinical and neuropathological phenotypes. Recent
      studies revealed that Abeta assemblies might have structural differences among AD
      brains and that such pleomorphic assemblies can correlate with distinct disease
      phenotypes. We found that in both sporadic and inherited forms of AD, amyloid
      aggregates differ in the biochemical composition of Abeta species. These
      differences affect the physicochemical properties of Abeta assemblies including
      aggregation kinetics, resistance to degradation by proteases and seeding ability.
      Abeta-amyloidosis can be induced and propagated in animal models by inoculation
      of brain extracts containing aggregated Abeta. We found that brain homogenates
      from AD patients with different molecular profiles of Abeta are able to induce
      distinct patterns of Abeta-amyloidosis when injected into mice. Overall these
      data suggest that the assembly of mixtures of Abeta peptides into different Abeta
      seeds leads to the formation of distinct subtypes of amyloid having distinctive
      physicochemical and biological properties which result in the generation of
      distinct AD molecular subgroups.

PMID- 29459626
TI  - Comparative transcriptomics with self-organizing map reveals cryptic
      photosynthetic differences between two accessions of North American Lake cress.
AB  - Because natural variation in wild species is likely the result of local
      adaptation, it provides a valuable resource for understanding plant-environmental
      interactions. Rorippa aquatica (Brassicaceae) is a semi-aquatic North American
      plant with morphological differences between several accessions, but little
      information available on any physiological differences. Here, we surveyed the
      transcriptomes of two R. aquatica accessions and identified cryptic physiological
      differences between them. We first reconstructed a Rorippa phylogeny to confirm
      relationships between the accessions. We performed large-scale RNA-seq and de
      novo assembly; the resulting 87,754 unigenes were then annotated via comparisons
      to different databases. Between-accession physiological variation was identified
      with transcriptomes from both accessions. Transcriptome data were analyzed with
      principal component analysis and self-organizing map. Results of analyses
      suggested that photosynthetic capability differs between the accessions. Indeed,
      physiological experiments revealed between-accession variation in electron
      transport rate and the redox state of the plastoquinone pool. These results
      indicated that one accession may have adapted to differences in temperature or
      length of the growing season.

PMID- 29459628
TI  - Submarine slope failures due to pipe structure formation.
AB  - There is a strong spatial correlation between submarine slope failures and the
      occurrence of gas hydrates. This has been attributed to the dynamic nature of gas
      hydrate systems and the potential reduction of slope stability due to bottom
      water warming or sea level drop. However, 30 years of research into this process
      found no solid supporting evidence. Here we present new reflection seismic data
      from the Arctic Ocean and numerical modelling results supporting a different link
      between hydrates and slope stability. Hydrates reduce sediment permeability and
      cause build-up of overpressure at the base of the gas hydrate stability zone.
      Resulting hydro-fracturing forms pipe structures as pathways for overpressured
      fluids to migrate upward. Where these pipe structures reach shallow permeable
      beds, this overpressure transfers laterally and destabilises the slope. This
      process reconciles the spatial correlation of submarine landslides and gas
      hydrate, and it is independent of environmental change and water depth.

PMID- 29459627
TI  - Understanding the functional role of genistein in the bone differentiation in
      mouse osteoblastic cell line MC3T3-E1 by RNA-seq analysis.
AB  - Genistein, a phyto-estrogen, can potentially replace endogenous estrogens in
      postmenopausal women, but the underlying molecular mechanisms remain incompletely
      understood. To obtain insight into the effect of genistein on bone
      differentiation, RNA sequencing (RNA-seq) analysis was used to detect
      differentially expressed genes (DEGs) in genistein-treated vs. untreated MC3T3-E1
      mouse osteoblastic cells. Osteoblastic cell differentiation was monitored by
      measuring osteoblast differentiation factors (ALP production, bone
      mineralization, and expression of osteoblast differentiation markers). From RNA
      seq analysis, a total of 132 DEGs (including 52 up-regulated and 80 down
      regulated genes) were identified in genistein-treated cells (FDR q-value < 0.05
      and fold change > 1.5). KEGG pathway and Gene Ontology (GO) enrichment analyses
      were performed to estimate the biological functions of DEGs and demonstrated that
      these DEGs were highly enriched in functions related to chemotactic cytokines.
      The functional relevance of DEGs to genistein-induced osteoblastic cell
      differentiation was further evaluated by siRNA-mediated knockdown in MC3T3-E1
      cells. These siRNA knockdown experiments (of the DEGs validated by real-time
      qPCR) demonstrated that two up-regulated genes (Ereg and Efcab2) enhance
      osteoblastic cell differentiation, while three down-regulated genes (Hrc, Gli,
      and Ifitm5) suppress the differentiation. These results imply their major
      functional roles in bone differentiation regulated by genistein.

PMID- 29459629
TI  - Experimental study of the anti-tumour activity and pharmacokinetics of arctigenin
      and its valine ester derivative.
AB  - Arctigenin (ARG) is a functional active component that has important
      physiological and pharmacological activities. The anti-tumour and anti
      inflammatory activities of ARG show good potential for application and
      development, but this material has the defect of low water solubility. In this
      experiment, the valine derivative of ARG (ARG-V) was designed and synthesized to
      overcome this disadvantage. The ARG amino acid, EDCI and DMAP were raw materials
      in the addition reaction, with a molar ratio of 1:2:2:0.5. The yield of ARG-V was
      up to 80%. ARG-V has strong anti-tumour activity in vivo and in vitro. The
      inhibitory rate of ARG-V was 69.2%, with less damage to the immune organs and
      different degrees of increased serum cytotoxicity. Moreover, the pharmacokinetics
      of ARG following oral administration and ARG-V following oral administration in
      rats were also studied. The Cmax and AUC values of ARG-V showed significant
      differences compared to ARG. The relative bioavailabilities of three doses of ARG
      V compared to ARG were 664.7%, 741.5% and 812.9%. These pharmacokinetic results
      may be useful for further studies of the bioactive mechanism of ARG and provide a
      theoretical basic for clinical use.

PMID- 29459630
TI  - Development of ultra-deep targeted RNA sequencing for analyzing X-chromosome
      inactivation in female Dent disease.
AB  - The pattern of X-chromosome inactivation (XCI) can affect the clinical severity
      of X-linked disorders in females. XCI pattern analysis has been conducted mainly
      by HUMARA assay, a polymerase chain reaction-based assay using a methylation
      sensitive restriction enzyme. However, this assay examines the XCI ratio of the
      androgen receptor gene at the genomic DNA level and does not reflect the ratio of
      either targeted gene directly or at the mRNA level. Here, we report four females
      with Dent disease, and we clarified the correlation between XCI and female cases
      of Dent disease using not only HUMARA assay but also a novel analytical method by
      RNA sequencing. We constructed genetic analysis for 4 female cases showing high
      level of urinary low-molecular-weight proteinuria and their parents. Their XCI
      pattern was analyzed by both HUMARA assay and an ultra-deep targeted RNA
      sequencing of the CLCN5 gene using genomic DNA and mRNA extracted from both
      leukocytes and urine sediment. All four cases possessed pathogenic variants of
      the CLCN5 gene. XCI analysis revealed skewed XCI in only two cases, while the
      other two showed random XCI. All assay results of HUMARA and targeted RNA
      sequencing in both leukocytes and urinary sediment were clearly identical in all
      four cases. We developed a novel XCI analytical assay of ultra-deep targeted RNA
      sequencing and revealed that skewed XCI explains the mechanism of onset of female
      Dent disease in only half of such cases.

PMID- 29459631
TI  - Biochemical validation of EHMT1 missense mutations in Kleefstra syndrome.
AB  - Kleefstra syndrome (KS) (9q34 deletion syndrome) is a rare autosomal dominant
      disorder characterized by intellectual disability, frequently coupled with a
      spectrum of complex physical and clinical manifestations. As the euchromatic
      histone methyltransferase-1 gene (EHMT1, GLP, or KMT1D) within the 9q34 region is
      deleted or mutated in most of the individuals with KS, its absence or defect in
      one allele is speculated to cause the major symptoms of the syndrome. Most of the
      EHMT1 mutations are frameshift or nonsense mutations, but two individuals with KS
      were reported to possess EHMT1 missense mutations. These two mutations have been
      predicted to cause a defective enzymatic function, but precise biochemical
      validation was not conducted. Therefore, we validated these two mutations by
      performing in vitro histone methyltransferase (HMT) activity assay and found that
      C1073Y and R1197W mutations severely affected the HMT activity. Additionally, the
      same amino-acid substitutions in mouse GLP induced impairment of in vivo GLP
      function. Furthermore, these two EHMT1 mutants showed defective heterocomplex
      formation with G9a (partner HMT) which is essential for their in vivo HMT
      function. Conclusively, our biochemical characterization clearly demonstrates
      that the previously reported two missense mutations of EHMT1 deteriorate HMT
      activity and GLP function, which presumably cause KS.

PMID- 29459632
TI  - Publisher Correction: Intercalation events visualized in single microcrystals of
      graphite.
AB  - The Peer Review File associated with this Article was updated shortly after
      publication to redact confidential comments to the editor.

PMID- 29459633
TI  - Self-calibrating d-scan: measuring ultrashort laser pulses on-target using an
      arbitrary pulse compressor.
AB  - In most applications of ultrashort pulse lasers, temporal compressors are used to
      achieve a desired pulse duration in a target or sample, and precise temporal
      characterization is important. The dispersion-scan (d-scan) pulse
      characterization technique usually involves using glass wedges to impart
      variable, well-defined amounts of dispersion to the pulses, while measuring the
      spectrum of a nonlinear signal produced by those pulses. This works very well for
      broadband few-cycle pulses, but longer, narrower bandwidth pulses are much more
      difficult to measure this way. Here we demonstrate the concept of self
      calibrating d-scan, which extends the applicability of the d-scan technique to
      pulses of arbitrary duration, enabling their complete measurement without prior
      knowledge of the introduced dispersion. In particular, we show that the pulse
      compressors already employed in chirped pulse amplification (CPA) systems can be
      used to simultaneously compress and measure the temporal profile of the output
      pulses on-target in a simple way, without the need of additional diagnostics or
      calibrations, while at the same time calibrating the often-unknown differential
      dispersion of the compressor itself. We demonstrate the technique through
      simulations and experiments under known conditions. Finally, we apply it to the
      measurement and compression of 27.5 fs pulses from a CPA laser.

PMID- 29459634
TI  - Multiple Kernel Learning Model for Relating Structural and Functional
      Connectivity in the Brain.
AB  - A challenging problem in cognitive neuroscience is to relate the structural
      connectivity (SC) to the functional connectivity (FC) to better understand how
      large-scale network dynamics underlying human cognition emerges from the
      relatively fixed SC architecture. Recent modeling attempts point to the
      possibility of a single diffusion kernel giving a good estimate of the FC. We
      highlight the shortcomings of the single-diffusion-kernel model (SDK) and propose
      a multi-scale diffusion scheme. Our multi-scale model is formulated as a reaction
      diffusion system giving rise to spatio-temporal patterns on a fixed topology. We
      hypothesize the presence of inter-regional co-activations (latent parameters)
      that combine diffusion kernels at multiple scales to characterize how FC could
      arise from SC. We formulated a multiple kernel learning (MKL) scheme to estimate
      the latent parameters from training data. Our model is analytically tractable and
      complex enough to capture the details of the underlying biological phenomena. The
      parameters learned by the MKL model lead to highly accurate predictions of
      subject-specific FCs from test datasets at a rate of 71%, surpassing the
      performance of the existing linear and non-linear models. We provide an example
      of how these latent parameters could be used to characterize age-specific
      reorganization in the brain structure and function.

PMID- 29459635
TI  - Multiresolution Consensus Clustering in Networks.
AB  - Networks often exhibit structure at disparate scales. We propose a method for
      identifying community structure at different scales based on multiresolution
      modularity and consensus clustering. Our contribution consists of two parts.
      First, we propose a strategy for sampling the entire range of possible
      resolutions for the multiresolution modularity quality function. Our approach is
      directly based on the properties of modularity and, in particular, provides a
      natural way of avoiding the need to increase the resolution parameter by several
      orders of magnitude to break a few remaining small communities, necessitating the
      introduction of ad-hoc limits to the resolution range with standard sampling
      approaches. Second, we propose a hierarchical consensus clustering procedure,
      based on a modified modularity, that allows one to construct a hierarchical
      consensus structure given a set of input partitions. While here we are interested
      in its application to partitions sampled using multiresolution modularity, this
      consensus clustering procedure can be applied to the output of any clustering
      algorithm. As such, we see many potential applications of the individual parts of
      our multiresolution consensus clustering procedure in addition to using the
      procedure itself to identify hierarchical structure in networks.

PMID- 29459636
TI  - On mechanical behaviors of few-layer black phosphorus.
AB  - This paper investigates the mechanical behaviors of few-layer black phosphorus
      (FLBP) by using molecular dynamics simulations. Results show that both tensile
      and compressive behaviors are strongly anisotropic in the armchair and zigzag
      directions due to the unidirectional puckers in each atomic layer, and that the
      compressive behavior is dependent on the number of atomic layers. In particular,
      the compressive and buckling strengths of FLBP can be significantly enhanced by
      stacking more atomic layers together, while this has little influence on both
      Young's modulus and tensile strength. It is interesting to found that increasing
      the number of atomic layers in FLBP or the dimension ratio can lead to a
      drastically reduced flexibility in armchair direction, showing that both
      compressive and buckling strengths become higher than those in zigzag direction.
      It is also demonstrated that the reorientation of FLBP's atomic configuration
      occurs under certain conditions. The mechanism of deformation underlying the
      mechanical behaviors of FLBP is also discussed, suggesting that changing the
      number of atomic layers is an effective way to engineer two-dimensional materials
      for desired material properties.

PMID- 29459637
TI  - Angiotensin II-induced Hypertension is Reduced by Deficiency of P-selectin
      Glycoprotein Ligand-1.
AB  - Identification of inflammatory mediators that regulate the vascular response to
      vasopressor molecules may aid in the development of novel therapeutic agents to
      treat or prevent hypertensive vascular diseases. Leukocytes have recently been
      shown to be capable of modifying blood pressure responses to vasopressor
      molecules. The purpose of this study was to test the hypothesis that deficiency
      of the leukocyte ligand, Psgl-1, would reduce the pressor response to angiotensin
      II (Ang II). Mice deficient in Psgl-1 (Psgl-1-/-) along with wild-type (WT)
      controls were treated for 2 weeks with a continuous infusion of Ang II. No
      differences in blood pressure between the groups were noted at baseline, however
      after 5 days of Ang II infusion, systolic blood pressures were higher in WT
      compared to Psgl-1-/- mice. The pressor response to acute administration of high
      dose Ang II was also attenuated in Psgl-1-/- compared to WT mice. Chimeric mice
      with hematopoietic deficiency of Psgl-1 similarly showed a reduced pressor
      response to Ang II. This effect was associated with reduced plasma interleukin-17
      (IL-17) levels in Psgl-1-/- mice and the reduced pressor response was restored by
      administration of recombinant IL-17. In conclusion, hematopoietic deficiency of
      Psgl-1 attenuates Ang II-induced hypertension, an effect that may be mediated by
      reduced IL-17.

PMID- 29459638
TI  - Insight into induced charges at metal surfaces and biointerfaces using a
      polarizable Lennard-Jones potential.
AB  - Metallic nanostructures have become popular for applications in therapeutics,
      catalysts, imaging, and gene delivery. Molecular dynamics simulations are gaining
      influence to predict nanostructure assembly and performance; however,
      instantaneous polarization effects due to induced charges in the free electron
      gas are not routinely included. Here we present a simple, compatible, and
      accurate polarizable potential for gold that consists of a Lennard-Jones
      potential and a harmonically coupled core-shell charge pair for every metal atom.
      The model reproduces the classical image potential of adsorbed ions as well as
      surface, bulk, and aqueous interfacial properties in excellent agreement with
      experiment. Induced charges affect the adsorption of ions onto gold surfaces in
      the gas phase at a strength similar to chemical bonds while ions and charged
      peptides in solution are influenced at a strength similar to intermolecular
      bonds. The proposed model can be applied to complex gold interfaces, electrode
      processes, and extended to other metals.

PMID- 29459639
TI  - Imaging genotyping of functional signaling pathways in lung squamous cell
      carcinoma using a radiomics approach.
AB  - Imaging features can be useful for identifying distinct genomic differences and
      have predictive power for certain phenotypes attributed to genomic mutations. We
      aimed to identify predictive imaging biomarkers that underpin genomic alterations
      and clinical outcomes in lung squamous cell carcinoma (SQCC) using a radiomics
      approach. In 57 patients with lung SQCC who underwent preoperative computed
      tomography (CT) and whole-exome DNA sequencing, 63 quantitative imaging features
      were extracted from CT and 73 clinicoradiological features including imaging
      features were classified into 8 categories: clinical, global, histogram-based,
      lung cancer-specific, shape, local, regional, and emphysema. Mutational profiles
      for core signaling pathways of lung SQCC were classified into five categories:
      redox stress, apoptosis, proliferation, differentiation, and chromatin
      remodelers. Range and right lung volume was significantly associated with
      alternation of apoptosis and proliferation pathway (p = 0.03, and p = 0.03).
      Energy was associated with the redox stress pathway (p = 0.06). None of the
      clinicoradiological features showed any significant association with the
      alteration of differentiation and chromatin remodelers pathway. This study showed
      that radiomic features indicating five different functional pathways of lung SQCC
      were different form one another. Radiomics approaches to lung SQCC have the
      potential to noninvasively predict alterations in core signaling pathways and
      clinical outcome.

PMID- 29459640
TI  - Self-assembled Collagen-Fibrin Hydrogel Reinforces Tissue Engineered Adventitia
      Vessels Seeded with Human Fibroblasts.
AB  - Efforts for tissue engineering vascular grafts focuses on the tunica media and
      intima, although the tunica adventitia serves as the primary structural support
      for blood vessels. In surgery, during endarterectomies, surgeons can strip the
      vessel, leaving the adventitia as the main strength layer to close the vessel.
      Here, we adapted our recently developed technique of forming vascular tissue
      rings then stacking the rings into a tubular structure, to accommodate human
      fibroblasts to create adventitia vessels in 8 days. Collagen production and
      fibril cross-linking was augmented with TGF-beta and ascorbic acid, significantly
      increasing tensile strength to 57.8 +/- 3.07 kPa (p = 0.008). Collagen type I gel
      was added to the base fibrin hydrogel to further increase strength. Groups were:
      Fibrin only; 0.7 mg/ml COL; 1.7 mg/ml COL; and 2.2 mg/ml COL. The 0.7 mg/ml
      collagen rings resulted in the highest tensile strength at 77.0 +/- 18.1 kPa (p =
      0.015). Culture periods of 1-2 weeks resulted in an increase in extracellular
      matrix deposition and significantly higher failure strength but not ultimate
      tensile strength. Histological analysis showed the 0.7 mg/ml COL group had
      significantly more, mature collagen. Thus, a hydrogel of 0.7 mg/ml collagen in
      fibrin was ideal for creating and strengthening engineered adventitia vessels.

PMID- 29459642
TI  - Decontamination of Petroleum-Contaminated Soils Using The Electrochemical
      Technique: Remediation Degree and Energy Consumption.
AB  - Currently, there are different remediation technologies for contaminated soils,
      but the selection of the best technology must be not only the treatment
      efficiency but also the energy consumption (costs) during its application. This
      paper is focused on assessing energy consumption related to the electrochemical
      treatment of polluted soil with petroleum hydrocarbons. In the framework of a
      research project, two types of experiments were conducted using soil that was
      artificially contaminated with diesel fuel at the same level of contamination.
      The experimental conditions considered for each experiment were: different
      amounts of contaminated soils (6 kg and 18 kg, respectively), the same current
      intensity level (0.25A and 0.5A), three different contamination degrees (1%, 2.5%
      and 5%) and the same time for application of the electrochemical treatment. The
      remediation degree concerning the removal of petroleum hydrocarbons from soil
      increased over time by approximately 20% over 7 days. With regard to energy
      consumption, the results revealed that with an increase in the quantity of
      treated soil of approximately three times, the specific energy consumption
      decreased from 2.94 kWh/kg treated soil to 1.64 kWh/kg treated soil.

PMID- 29459643
TI  - Immunotherapy: Cancer immunotherapy and the value of cure.

PMID- 29459644
TI  - Immunotherapy: CAR T cell therapy efficacious against B-ALL across age groups.

PMID- 29459641
TI  - Therapeutic effects of diclofenac, pregabalin, and duloxetine on disuse-induced
      chronic musculoskeletal pain in rats.
AB  - The aim of this study was to clarify the mechanism of disuse-induced muscle
      hyperalgesia through the evaluation of the pharmacological behaviour of muscle
      hyperalgesia profiles in chronic post-cast pain (CPCP) rats with acute and
      chronic-phase mirror-image muscle hyperalgesia treated with diclofenac (NSAID),
      pregabalin (an inhibitor of Ca2+ channel alpha2delta), and duloxetine (SNRI).
      After 2 weeks of cast immobilization, the peak cross-sectional area and muscle
      wet weight of the ipsilateral soleus and gastrocnemius muscles decreased more
      significantly in CPCP rats than in untreated rats. Histological findings revealed
      disuse-induced muscle atrophy in CPCP rats. The blood biochemical parameters of
      CPCP rats in acute and chronic phases did not differ significantly from those of
      untreated rats. The diclofenac and pregabalin-treated groups exhibited no
      improvement in acute or chronic muscle hyperalgesia. In contrast, the duloxetine
      treated group exhibited an improvement in acute muscle hyperalgesia, but showed
      no apparent effect on chronic muscle hyperalgesia on ipsilateral or contralateral
      sides. However, the chronic muscle hyperalgesia was reversed by intrathecal
      administration of DAMGO (a MU-opioid receptor agonist). The results suggest that
      chronic muscle hyperalgesia in CPCP rats did not result from an inflammatory
      mechanism, and there is only a low probability that it's caused by a neuropathic
      mechanism.

PMID- 29459645
TI  - Inhibition of ATG12-mediated autophagy by miR-214 enhances radiosensitivity in
      colorectal cancer.
AB  - Radioresistance hampers success in the treatment of patients with advanced
      colorectal cancer (CRC). Improving our understanding of the underlying mechanisms
      of radioresistance could increase patients' response to irradiation (IR).
      MicroRNAs are a class of small RNAs involved in tumor therapy response to
      radiation. Here we found that miR-214 was markedly decreased in CRC cell lines
      and blood of CRC patients after IR exposure. Meanwhile, autophagy was enhanced in
      irradiated CRC cells. Mechanically, ATG12 was predicted and identified as a
      direct target of miR-214 by dual luciferase assay, qPCR, and Western blot. In
      vitro and in vivo experiments showed that miR-214 promoted radiosensitivity by
      inhibiting IR-induced autophagy. Restoration of ATG12 attenuated miR-214-mediated
      inhibition of cell growth and survival in response to IR. Importantly, miR-214
      was highly expressed in radiosensitive CRC specimens and negatively correlated
      with plasma level of CEA. Moreover, ATG12 and LC3 expressions were increased in
      radioresistant CRC specimens. Our study elucidates that miR-214 promotes
      radiosensitivity by inhibition of ATG12-mediated autophagy in CRC. Importantly,
      miR-214 is a determinant of CRC irradiation response and may serve as a potential
      therapeutic target in CRC treatment.

PMID- 29459646
TI  - Poly(butylene succinate)/bamboo powder blends as solid-phase carbon source and
      biofilm carrier for denitrifying biofilters treating wastewater from
      recirculating aquaculture system.
AB  - In this study, Poly(butylene succinate)/bamboo powder (PBS/BP) was newly applied
      and tested for 8 months as the carbon source in two moving bed reactors for
      nitrate removal in real RAS wastewater (fresh/sea water), with the purposes of
      simultaneous reducing the cost of PBS packing and effluent DOC. Fast start-ups
      were obtained in both reactors, in which high denitrification rates were observed
      (0.68 +/- 0.03 and 0.83 +/- 0.11 kg [Formula: see text]-N m-3 d-1 for fresh and
      sea water, respectively) with no nitrite and low ammonia accumulation. Reduced
      DOC concentrations in the effluents were also observed compared to pure PBS. The
      freezing of PBS/BP showed a further slower release of DOC, which might be
      beneficial to the life of the PBS/BP for the denitrification process, however,
      microbial activity, especially in high salinity wastewater, was observed to have
      declined. Illumina sequencing revealed that the autotrophic genus arcobacter was
      discovered first time in solid-phase denitrification system with salinity.
      Redundancy analysis (RDA) was used to reveal the relationships between
      environmental factors and the microbial community. In overall, PBS/BP blends were
      proven to be an economically attractive carbon source for nitrate removal in RAS.

PMID- 29459647
TI  - Life history and biocontrol potential of the first female-producing
      parthenogenetic species of Diglyphus (Hymenoptera: Eulophidae) against agromyzid
      leafminers.
AB  - Diglyphus species are dominant biocontrol agents for suppressing outbreaks of
      agromyzid leafminers in fields. In July 2015, we collected a new thelytokous
      species of Diglyphus in Qinghai, China. The wasp is here named as D. wani Liu,
      Zhu & Yefremova sp. nov., based on morphological and molecular analyses. The life
      history and biocontrol potential of the wasp were studied in the laboratory and
      by providing Liriomyza sativae larvae. The intrinsic rate of increase, finite
      rate of increase, and mean generation time were 0.2373 d-1, 1.2678 d-1, and 15.9
      d, respectively. The wasps showed three types of host-killing behaviour, namely
      parasitism, host feeding and host stinging, resulting in 47.6, 94.4 and 3.4 host
      larvae killed per wasp over a lifetime, respectively. The finite total host
      killing rate was 1.0071 and the wasp showed strong synovigeny. The wasp may be a
      crucial biocontrol agent against agromyzid leafminers.

PMID- 29459648
TI  - Global Peak in Atmospheric Radiocarbon Provides a Potential Definition for the
      Onset of the Anthropocene Epoch in 1965.
AB  - Anthropogenic activity is now recognised as having profoundly and permanently
      altered the Earth system, suggesting we have entered a human-dominated geological
      epoch, the 'Anthropocene'. To formally define the onset of the Anthropocene, a
      synchronous global signature within geological-forming materials is required.
      Here we report a series of precisely-dated tree-ring records from Campbell Island
      (Southern Ocean) that capture peak atmospheric radiocarbon (14C) resulting from
      Northern Hemisphere-dominated thermonuclear bomb tests during the 1950s and
      1960s. The only alien tree on the island, a Sitka spruce (Picea sitchensis),
      allows us to seasonally-resolve Southern Hemisphere atmospheric 14C,
      demonstrating the 'bomb peak' in this remote and pristine location occurred in
      the last-quarter of 1965 (October-December), coincident with the broader changes
      associated with the post-World War II 'Great Acceleration' in industrial capacity
      and consumption. Our findings provide a precisely-resolved potential Global
      Stratotype Section and Point (GSSP) or 'golden spike', marking the onset of the
      Anthropocene Epoch.

PMID- 29459649
TI  - Evolving Bacterial Fitness with an Expanded Genetic Code.
AB  - Since the fixation of the genetic code, evolution has largely been confined to 20
      proteinogenic amino acids. The development of orthogonal translation systems that
      allow for the codon-specific incorporation of noncanonical amino acids may
      provide a means to expand the code, but these translation systems cannot be
      simply superimposed on cells that have spent billions of years optimizing their
      genomes with the canonical code. We have therefore carried out directed evolution
      experiments with an orthogonal translation system that inserts 3-nitro-L-tyrosine
      across from amber codons, creating a 21 amino acid genetic code in which the
      amber stop codon ambiguously encodes either 3-nitro-L-tyrosine or stop. The 21
      amino acid code is enforced through the inclusion of an addicted, essential gene,
      a beta-lactamase dependent upon 3-nitro-L-tyrosine incorporation. After 2000
      generations of directed evolution, the fitness deficit of the original strain was
      largely repaired through mutations that limited the toxicity of the noncanonical.
      While the evolved lineages had not resolved the ambiguous coding of the amber
      codon, the improvements in fitness allowed new amber codons to populate protein
      coding sequences.

PMID- 29459650
TI  - A dual-mode mobile phone microscope using the onboard camera flash and ambient
      light.
AB  - Mobile phone microscopes are a natural platform for point-of-care imaging, but
      current solutions require an externally powered illumination source, thereby
      adding bulk and cost. We present a mobile phone microscope that uses the internal
      flash or sunlight as the illumination source, thereby reducing complexity whilst
      maintaining functionality and performance. The microscope is capable of both
      brightfield and darkfield imaging modes, enabling microscopic visualisation of
      samples ranging from plant to mammalian cells. We describe the microscope design
      principles, assembly process, and demonstrate its imaging capabilities through
      the visualisation of unlabelled cell nuclei to observing the motility of cattle
      sperm and zooplankton.

PMID- 29459651
TI  - Crystal structure of the hydroxylaminopurine resistance protein, YiiM, and its
      putative molybdenum cofactor-binding catalytic site.
AB  - The molybdenum cofactor (Moco) is a molybdenum-conjugated prosthetic group that
      is ubiquitously found in plants, animals, and bacteria. Moco is required for the
      nitrogen-reducing reaction of the Moco sulfurase C-terminal domain (MOSC) family.
      Despite the biological significance of MOSC proteins in the conversion of
      prodrugs and resistance against mutagens, their structural features and Moco
      mediated catalysis mechanism have not been described in detail. YiiM is a MOSC
      protein that is involved in reducing mutagenic 6-N-hydroxylaminopurine to
      nontoxic adenine in bacteria. Here, we report two crystal structures of YiiM: one
      from Gram-positive Geobacillus stearothermophilus (gsYiiM) and the other from
      Gram-negative Escherichia coli (ecYiiM). Although gsYiiM and ecYiiM differ in
      oligomerization state and protein stability, both consist of three structural
      modules (a beta-barrel and two alpha-helix bundles) and feature a cavity
      surrounded by the three modules. The cavity is characterized by positive
      electrostatic potentials and high sequence conservation. Moreover, the ecYiiM
      cavity houses a phosphate group, which emulates a part of Moco, and contains a
      highly reactive invariant cysteine residue. We thus propose that the cavity is
      the catalytic site where Moco binds and the substrate is reduced. Moreover, our
      comparative structural analysis highlights the common but distinct structural
      features of MOSC proteins.

PMID- 29459652
TI  - Light touch.

PMID- 29459653
TI  - Strong room-temperature ferromagnetism in VSe2 monolayers on van der Waals
      substrates.
AB  - Reduced dimensionality and interlayer coupling in van der Waals materials gives
      rise to fundamentally different electronic 1 , optical 2 and many-body quantum3-5
      properties in monolayers compared with the bulk. This layer-dependence permits
      the discovery of novel material properties in the monolayer regime. Ferromagnetic
      order in two-dimensional materials is a coveted property that would allow
      fundamental studies of spin behaviour in low dimensions and enable new
      spintronics applications6-8. Recent studies have shown that for the bulk
      ferromagnetic layered materials CrI3 (ref. 9 ) and Cr2Ge2Te6 (ref. 10 ),
      ferromagnetic order is maintained down to the ultrathin limit at low
      temperatures. Contrary to these observations, we report the emergence of strong
      ferromagnetic ordering for monolayer VSe2, a material that is paramagnetic in the
      bulk11,12. Importantly, the ferromagnetic ordering with a large magnetic moment
      persists to above room temperature, making VSe2 an attractive material for van
      der Waals spintronics applications.

PMID- 29459654
TI  - Photoelectrochemical modulation of neuronal activity with free-standing coaxial
      silicon nanowires.
AB  - Optical methods for modulating cellular behaviour are promising for both
      fundamental and clinical applications. However, most available methods are either
      mechanically invasive, require genetic manipulation of target cells or cannot
      provide subcellular specificity. Here, we address all these issues by showing
      optical neuromodulation with free-standing coaxial p-type/intrinsic/n-type
      silicon nanowires. We reveal the presence of atomic gold on the nanowire
      surfaces, likely due to gold diffusion during the material growth. To evaluate
      how surface gold impacts the photoelectrochemical properties of single nanowires,
      we used modified quartz pipettes from a patch clamp and recorded sustained
      cathodic photocurrents from single nanowires. We show that these currents can
      elicit action potentials in primary rat dorsal root ganglion neurons through a
      primarily atomic gold-enhanced photoelectrochemical process.

PMID- 29459655
TI  - Longitudinal association of type 1 interferon-induced chemokines with disease
      activity in systemic lupus erythematosus.
AB  - Type I interferon (IFN) pathways are significant in SLE pathogenesis. Less is
      known about the utility of measuring markers of IFN activity in patients, or
      whether patient subsets with different profiles exist. We explored the
      longitudinal associations of IFN-induced chemokines with disease activity in a
      cohort of SLE patients. We calculated a validated composite score (IFN-CK) of
      three type I IFN-inducible chemokines (CCL2/CXCL10/CCL19) measured in 109 SLE
      patients (median 7 occasions over 3.2 years). Longitudinal associations of IFN-CK
      score with disease activity (SLEDAI-2K) and other variables were assessed using
      general estimating equation (GEE) methods. IFN-CK was detectable in all patients.
      SLEDAI-2K was significantly associated with IFN-CK, damage score and prednisolone
      dose. SLEDAI-2K remained significantly associated with IFN-CK over time after
      adjustment of covariates. Patients with high time-adjusted mean IFN-CK had lower
      complement and higher time-adjusted disease activity. Concordance between IFN-CK
      and SLEDAI-2K varied widely among patients, with some individuals having none,
      others weak, and a subset very high concordance. In summary in our cohort of SLE
      patients, serum IFN-CK varied over time with disease activity, but with wide
      variation in concordance. Differing relationships between IFN pathway activation
      and disease activity may be valuable in assigning patients to emerging IFN
      pathway targeting treatments.

PMID- 29459656
TI  - Electromyographic patterns of the rat hindlimb in response to muscle stretch
      after spinal cord injury.
AB  - STUDY DESIGN: Experimental Study. OBJECTIVES: To characterize the specific
      hindlimb electromyographic (EMG) patterns in response to muscle stretch and to
      measure the applied forces during stretching in the rat model of moderate SCI.
      SETTING: Kentucky Spinal Cord Injury Research Center, Louisville, KY, USA.
      METHODS: Female Sprague Dawley rats (n = 4) were instrumented for telemetry-based
      EMG recording (right rectus femoris and biceps femoris) and received a moderate
      T10 spinal cord injury (SCI). The major hindlimb muscle groups were stretched
      using our clinically modeled protocol. The EMG responses were recorded biweekly
      for 8 weeks. The forces applied during stretching were measured using a custom
      designed glove. Locomotor function was assessed using the BBB Open Field
      Locomotor Scale, 3D kinematics and gait analysis. RESULTS: Three main EMG
      patterns in response to stretch were identified: clonic-like, air-stepping, and
      spasms. Torques applied during stretching ranged from 0.4-8 N*cm, and with the
      exception of the quadriceps, did not change significantly over the weeks of
      stretching. Two stretching sessions a week did not result in a significant
      disruption to locomotor function. CONCLUSIONS: Stretching evokes EMG patterns in
      rats similar to those reported in humans including clonus and spasms. The torques
      used during stretching are comparable, based on the ratio of torque to body
      weight, to the few previously published studies that measured the forces and/or
      torques applied by physical therapists when stretching patients. Future studies
      are warranted to fully explore the impact of muscle stretch on spinal cord
      function after injury. SPONSORSHIP: DoD, KSCHIRT, NIH.

PMID- 29459657
TI  - Very long-/ and long Chain-3-Hydroxy Acyl CoA Dehydrogenase Deficiency correlates
      with deregulation of the mitochondrial fusion/fission machinery.
AB  - Children diagnosed with Long-Chain-3-Hydroxy-Acyl-CoA-Dehydrogenase-Deficiency
      (LCHADD) or Very-Long-Chain-3-Hydroxy-Acyl-CoA-Dehydrogenase-Deficiency (VLCADD)
      frequently present with hypertrophic cardiomyopathy or muscle weakness which is
      caused by the accumulation of fatty acid metabolites due to inactivating
      mutations in the mitochondrial trifunctional protein. By analyzing mitochondrial
      morphology we uncovered that mutations within the HADHA or the ACADVL gene not
      only affect fatty acid oxidation, but also cause significant changes in the
      DNM1L/MFN2 ratio leading to the significant accumulation of truncated and
      punctate mitochondria in contrast to network-like mitochondrial morphology in
      controls. These striking morphological abnormalities correlate with changes in
      OXPHOS, an imbalance in ROS levels, reduced mitochondrial respiration, reduced
      growth rates and significantly increased glucose uptake per cell, suggesting that
      HADHA and ACADVL mutations shift cellular energy household into glycolysis.
      Experiments using the NOX2-specific inhibitor Phox-I2 suggest that NOX2 is
      activated by accumulating long-chain fatty acids and generates ROS, which in turn
      changes mitochondrial morphology and activity. We thereby provide novel insights
      into the cellular energy household of cells from LCHADD/VLCADD patients and
      demonstrate for the first time a connection between fatty acid metabolism,
      mitochondrial morphology and ROS in patients with these rare genetic disorders.

PMID- 29459658
TI  - Chromosome biology: A stairway to mitotic chromosome assembly.

PMID- 29459659
TI  - Ultrafast electron-phonon coupling and photo-induced strain in the morphotropic
      phase boundary of BixDy1-xFeO3 films.
AB  - The interplay among ferroelectric, magnetic and elastic degrees of freedom in
      multiferroics is the key issues in condensed matters, which has been widely
      investigated by various methods. Here, using ultrafast two-color pump-probe
      spectroscopy, the picosecond electron-phonon and spin-lattice coupling process in
      Dysprosium doped-BiFeO3 (BDFO) films on SrTiO3 (STO) substrate have been
      investigated systematically. The Dy-doping induced structural transition and
      magnetic enhancement in BDFO is observed by ultrafast electron-phonon and spin
      lattice interaction, respectively. The elastic anomalies in BDFO films are
      revealed by the photo-induced coherent acoustic phonon. With increasing the Dy
      doping ratio, the frequencies of the acoustic phonon in the films are modulated,
      and the phonon transmission coefficient between films and substrate is found to
      approach unity gradually. The ultrafast observation of the tunability of the
      ferroelectric, magnetic and the elastic properties in the morphotropic phase
      boundary of rare-earth doped BFO films provides new insights into the integration
      of BFO in next-generation high frequency electro-magnetic and electroacoustic
      devices.

PMID- 29459660
TI  - Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat
      hepatotoxicity.
AB  - Small interfering RNAs (siRNAs) conjugated to a trivalent N-acetylgalactosamine
      (GalNAc) ligand are being evaluated in investigational clinical studies for a
      variety of indications. The typical development candidate selection process
      includes evaluation of the most active compounds for toxicity in rats at
      pharmacologically exaggerated doses. The subset of GalNAc-siRNAs that show rat
      hepatotoxicity is not advanced to clinical development. Potential mechanisms of
      hepatotoxicity can be associated with the intracellular accumulation of
      oligonucleotides and their metabolites, RNA interference (RNAi)-mediated
      hybridization-based off-target effects, and/or perturbation of endogenous RNAi
      pathways. Here we show that rodent hepatotoxicity observed at supratherapeutic
      exposures can be largely attributed to RNAi-mediated off-target effects, but not
      chemical modifications or the perturbation of RNAi pathways. Furthermore, these
      off-target effects can be mitigated by modulating seed-pairing using a thermally
      destabilizing chemical modification, which significantly improves the safety
      profile of a GalNAc-siRNA in rat and may minimize the occurrence of hepatotoxic
      siRNAs across species.

PMID- 29459661
TI  - Elements of the complete blood count associated with cardiovascular disease
      incidence: Findings from the EPIC-NL cohort study.
AB  - All blood cells (white blood cells [WBC], red blood cells [RBC] and platelets)
      can play a role in atherosclerosis. Complete blood count (CBC) is widely
      available in clinical practice but utility as potential risk factors for
      cardiovascular disease (CVD) is uncertain. Our aim was to assess the associations
      of pre-diagnostic CBC with incidence of CVD in 14,362 adults free of CVD and aged
      47.8 (+/-11.7) years at baseline, followed-up for 11.4 years (992 incident
      cases). Cox proportional hazards regressions were used to estimate HRs and 95%CI.
      Comparing the top (T3) to bottom (T1) tertile, increased total WBC, lymphocyte,
      monocyte and neutrophil counts were associated with higher CVD risk: 1.31 (1.10;
      1.55), 1.20 (1.02; 1.41), 1.21 (1.03; 1.41) and 1.24 (1.05; 1.47), as well as
      mean corpuscular volume (MCV: 1.23 [1.04; 1.46]) and red cell distribution width
      (RDW: 1.22 [1.03; 1.44]). Platelets displayed an association for count values
      above the clinically normal range: 1.49 (1.00; 2.22). To conclude, total and
      differential WBC count, MCV, RDW and platelet count likely play a role in the
      aetiology of CVD but only WBC provide a modest improvement for the prediction of
      10-year CVD risk over traditional CVD risk factors in a general population.

PMID- 29459662
TI  - Blast phase myeloproliferative neoplasm: Mayo-AGIMM study of 410 patients from
      two separate cohorts.
AB  - A total of 410 patients with blast phase myeloproliferative neoplasm (MPN-BP)
      were retrospectively reviewed: 248 from the Mayo Clinic and 162 from Italy.
      Median survival was 3.6 months, with no improvement over the last 15 years.
      Multivariable analysis performed on the Mayo cohort identified high risk
      karyotype, platelet count < 100 * 109/L, age > 65 years and transfusion need as
      independent risk factors for survival. Also in the Mayo cohort, intensive
      chemotherapy resulted in complete remission (CR) or CR with incomplete count
      recovery (CRi) rates of 35 and 24%, respectively; treatment-specified 3-year/5
      year survival rates were 32/10% for patients receiving allogeneic stem cell
      transplant (AlloSCT) (n = 24), 19/13% for patients achieving CR/CRi but were not
      transplanted (n = 24), and 1/1% in the absence of both AlloSCT and CR/CRi (n =
      200) (p < 0.01). The survival impact of AlloSCT (HR 0.2, 95% CI 0.1-0.3), CR/CRi
      without AlloSCT (HR 0.3, 95% CI 0.2-0.5), high risk karyotype (HR 1.6, 95% CI 1.1
      2.2) and platelet count < 100 * 109/L (HR 1.6, 95% CI 1.1-2.2) were confirmed to
      be inter-independent. Similar observations were made in the Italian cohort. The
      current study identifies the setting for improved short-term survival in MPN-BP,
      but also highlights the limited value of current therapy, including AlloSCT, in
      securing long-term survival.

PMID- 29459663
TI  - Tuning Infrared Plasmon Resonance of Black Phosphorene Nanoribbon with a
      Dielectric Interface.
AB  - We report on the tunable edge-plasmon-enhanced absorption of phosphorene
      nanoribbons supported on a dielectric substrate. Monolayer anisotropic black
      phosphorous (phosphorene) nanoribbons are explored for light trapping and
      absorption enhancement on different dielectric substrates. We show that these
      phosphorene ribbons support infrared surface plasmons with high spatial
      confinement. The peak position and bandwidth of the calculated phosphorene
      absorption spectra are tunable with low loss over a wide wavelength range via the
      surrounding dielectric environment of the periodic nanoribbons. Simulation
      results show strong edge plasmon modes and enhanced absorption as well as a red
      shift of the peak resonance wavelength. The periodic Fabry-Perot grating model
      was used to analytically evaluate the absorption resonance arising from the edge
      of the ribbons for comparison with the simulation. The results show promise for
      the promotion of phosphorene plasmons for both fundamental studies and potential
      applications in the infrared spectral range.

PMID- 29459665
TI  - A randomized, placebo-controlled pilot trial of aprepitant combined with standard
      antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting
      in patients undergoing cyclophosphamide-based conditioning regimens prior to
      hematopoietic stem cell transplant (HSCT).
AB  - The aim of this study was to evaluate the safety and efficacy of aprepitant when
      used prophylactically to prevent nausea and vomiting during cyclophosphamide
      based conditioning regimens. The primary objective of this study was to determine
      if there was a difference in the number of emesis-free days in patients who
      received aprepitant as compared to those who received placebo. This prospective,
      randomized, double blind, placebo-controlled study was performed in 40 adult
      patients who received a cyclophosphamide-containing HSCT conditioning regimen.
      Twenty patients were randomized to receive aprepitant, ondansetron, and
      dexamethasone, and 20 were randomized to receive placebo, ondansetron, and
      dexamethasone. Complete response (CR) was defined as the absence of emesis and
      the absence of mild to moderate nausea. The average number of emesis-free days
      was 14.25 (standard deviation 1.48 days) in the aprepitant group compared to
      12.45 days (standard deviation 2.16 days) for patients in the placebo group.
      Eight patients (40%) in the aprepitant group achieved CR as compared to four
      patients (20%) in the placebo group. In the setting of cyclophosphamide
      containing conditioning regimens, the addition of aprepitant to a standard
      antiemetic regimen decreased the incidence of emesis as compared to placebo.
      Aprepitant was well tolerated.

PMID- 29459664
TI  - The putative anti-leukemic effects of anti-thymocyte globulins in patients with
      CD7-positive acute myeloid leukemia.
AB  - Polyclonal anti-thymocyte globulins (ATGs) are widely used in allogeneic stem
      cell transplantation (allo-SCT) for GvHD prophylaxis. ATGs exerted anti-tumor
      effects in in vitro experiments, but in vivo studies are lacking. We experienced
      a case of relapsed AML with cells positive for CD7 who underwent haploidentical
      SCT and unexpectedly achieved a significant reduction of AML cells in the
      peripheral blood after receiving ATGs before the administration of other drugs in
      the conditioning regimen. This patient achieved long-term survival after
      haploidentical SCT. To assess the impact of ATGs on clinical outcomes in patients
      with AML, we performed a retrospective analysis of allo-SCT for
      relapsed/refractory AML and divided 132 patients into four groups according to
      the expression of CD7 in AML cells and use of ATGs as part of the conditioning
      regimen, as follows: CD7-positive ATG group (n = 15), CD7-positive no-ATG group
      (n = 32), CD7-negative ATG group (n = 19), and CD7-negative no-ATG group (n =
      66). The overall survival rates in the CD7-positive ATG group were significantly
      higher than those in the CD7-positive no-ATG group, whereas these rates did not
      differ statistically between the CD7-negative ATG and CD7-negative no-ATG groups.
      Our results indicate a possible anti-leukemic effect of ATGs against CD7-positive
      AML in humans.

PMID- 29459666
TI  - Substantial Seasonal Contribution of Observed Biogenic Sulfate Particles to Cloud
      Condensation Nuclei.
AB  - Biogenic sources contribute to cloud condensation nuclei (CCN) in the clean
      marine atmosphere, but few measurements exist to constrain climate model
      simulations of their importance. The chemical composition of individual
      atmospheric aerosol particles showed two types of sulfate-containing particles in
      clean marine air masses in addition to mass-based Estimated Salt particles. Both
      types of sulfate particles lack combustion tracers and correlate, for some
      conditions, to atmospheric or seawater dimethyl sulfide (DMS) concentrations,
      which means their source was largely biogenic. The first type is identified as
      New Sulfate because their large sulfate mass fraction (63% sulfate) and
      association with entrainment conditions means they could have formed by
      nucleation in the free troposphere. The second type is Added Sulfate particles
      (38% sulfate), because they are preexisting particles onto which additional
      sulfate condensed. New Sulfate particles accounted for 31% (7 cm-3) and 33% (36
      cm-3) CCN at 0.1% supersaturation in late-autumn and late-spring, respectively,
      whereas sea spray provided 55% (13 cm-3) in late-autumn but only 4% (4 cm-3) in
      late-spring. Our results show a clear seasonal difference in the marine CCN
      budget, which illustrates how important phytoplankton-produced DMS emissions are
      for CCN in the North Atlantic.

PMID- 29459667
TI  - Expedient syntheses of N-heterocycles via intermolecular amphoteric diamination
      of allenes.
AB  - Saturated 1,4-diazo heterocycles including piperazines, 1,4-diazepanes, and 1,4
      diazocanes, are highly important for therapeutic development, but their syntheses
      are often tedious. We describe here an amphoteric diamination strategy to unite
      readily available 1,2-, 1,3- or 1,4-diamine derivatives with electron-deficient
      allenes via a formal [n + 2] (n = 4, 5, 6) cyclization mode to produce the
      corresponding 1,4-diazo heterocycles in just one step. This strategy features
      mild reaction conditions, high functional group tolerance, and scalability (gram
      scale). The reagents used are cheap and readily available and no transition metal
      catalysts are needed. More sophisticated products containing trifluoromethyl
      group or bicyclic ring systems can be accessed via a one-pot procedure as well.
      Our mechanistic studies support that formation of mono-iodinated or chlorinated
      diamine intermediates is important for the desired transformation and the
      commonly proposed chloride-iodide exchange process and a radical N-C bond
      formation is unlikely when the combination of NCS/KI is used.

PMID- 29459668
TI  - Photoconductivity of acid exfoliated and flash-light-processed MoS2 films.
AB  - MoS2 has been studied intensively during recent years as a semiconducting
      material in several fields, including optoelectronics, for applications such as
      solar cells and phototransistors. The photoresponse mechanisms of MoS2 have been
      discussed but are not fully understood, especially the phenomenon in which the
      photocurrent slowly increases. Here, we report on a study of the photoresponse
      flash-light-processed MoS2 films of different thicknesses and areas. The
      photoresponse of such films under different light intensities and bias voltages
      was measured, showing significant current changes with a quick response followed
      by a slow one upon exposure to pulsed light. Our in-depth study suggested that
      the slow response was due to the photothermal effect that heats the MoS2; this
      hypothesis was supported by the resistivity change at different temperatures. The
      results obtained from MoS2 films with various thicknesses indicated that the
      minority-carrier diffusion length was 1.36 um. This study explained the mechanism
      of the slow response of the MoS2 film and determined the effective thickness of
      MoS2 for a photoresponse to occur. The method used here for fabricating MoS2
      films could be used for fabricating optoelectronic devices due to its simplicity.

PMID- 29459669
TI  - Isoniazid resistance levels of Mycobacterium tuberculosis can largely be
      predicted by high-confidence resistance-conferring mutations.
AB  - The majority of Mycobacterium tuberculosis isolates resistant to isoniazid
      harbour a mutation in katG. Since these mutations cause a wide range of minimum
      inhibitory concentrations (MICs), largely below the serum level reached with
      higher dosing (15 mg/L upon 15-20 mg/kg), the drug might still remain partly
      active in presence of a katG mutation. We therefore investigated which genetic
      mutations predict the level of phenotypic isoniazid resistance in clinical M.
      tuberculosis isolates. To this end, the association between known and unknown
      isoniazid resistance-conferring mutations in whole genome sequences, and the
      isoniazid MICs of 176 isolates was examined. We found mostly moderate-level
      resistance characterized by a mode of 6.4 mg/L for the very common katG Ser315Thr
      mutation, and always very high MICs (>=19.2 mg/L) for the combination of katG
      Ser315Thr and inhA c-15t. Contrary to common belief, isolates harbouring inhA c
      15t alone, partly also showed moderate-level resistance, particularly when
      combined with inhA Ser94Ala. No overt association between low-confidence or
      unknown mutations, except in katG, and isoniazid resistance (level) was found.
      Except for the rare katG deletion, line probe assay is thus not sufficiently
      accurate to predict the level of isoniazid resistance for a single mutation in
      katG or inhA.

PMID- 29459670
TI  - An unusual type of polymorphism in a liquid crystal.
AB  - Polymorphism is a remarkable concept in chemistry, materials science, computer
      science, and biology. Whether it is the ability of a material to exist in two or
      more crystal structures, a single interface connecting to two different entities,
      or alternative phenotypes of an organism, polymorphism determines function and
      properties. In materials science, polymorphism can be found in an impressively
      wide range of materials, including crystalline materials, minerals, metals,
      alloys, and polymers. Here we report on polymorphism in a liquid crystal. A bent
      core liquid crystal with a single chiral side chain forms two structurally and
      morphologically significantly different liquid crystal phases solely depending on
      the cooling rate from the isotropic liquid state. On slow cooling, the
      thermodynamically more stable oblique columnar phase forms, and on rapid cooling,
      a not heretofore reported helical microfilament phase. Since structure determines
      function and properties, the structural color for these phases also differs.

PMID- 29459671
TI  - In silico guided reconstruction and analysis of ICAM-1-binding var genes from
      Plasmodium falciparum.
AB  - The Plasmodium falciparum variant surface antigen PfEMP1 expressed on the surface
      of infected erythrocytes is thought to play a major role in the pathology of
      severe malaria. As the sequence pool of the var genes encoding PfEMP1 expands
      there are opportunities, despite the high degree of sequence diversity
      demonstrated by this gene family, to reconstruct full-length var genes from small
      sequence tags generated from patient isolates. To test whether this is possible
      we have used a set of recently laboratory adapted ICAM-1-binding parasite
      isolates to generate sequence tags and, from these, to identify the full-length
      PfEMP1 being expressed by them. In a subset of the strains available we were able
      to produce validated, full-length var gene sequences and use these to conduct
      biophysical analyses of the ICAM-1 binding regions.

PMID- 29459672
TI  - Route to high-energy density polymeric nitrogen t-N via He-N compounds.
AB  - Polymeric nitrogen, stabilized by compressing pure molecular nitrogen, has yet to
      be recovered to ambient conditions, precluding its application as a high-energy
      density material. Here we suggest a route for synthesis of a tetragonal polymeric
      nitrogen, denoted t-N, via He-N compounds at high pressures. Using first
      principles calculations with structure searching, we predict a class of nitrides
      with stoichiometry HeN4 that are energetically stable (relative to a mixture of
      solid He and N2) above 8.5 GPa. At high pressure, HeN4 comprises a polymeric
      channel-like nitrogen framework filled with linearly arranged helium atoms. The
      nitrogen framework persists to ambient pressure on decompression after removal of
      helium, forming pure polymeric nitrogen, t-N. t-N is dynamically and mechanically
      stable at ambient pressure with an estimated energy density of ~11.31 kJ/g,
      marking it out as a remarkable high-energy density material. This expands the
      known polymeric forms of nitrogen and indicates a route to its synthesis.

PMID- 29459673
TI  - Specific Recognition of Arginine Methylated Histone Tails by JMJD5 and JMJD7.
AB  - We have reported that JMJD5 and JMJD7 (JMJD5/7) are responsible for the clipping
      of arginine methylated histone tails to generate "tailless nucleosomes", which
      could release the pausing RNA polymerase II (Pol II) into productive
      transcription elongation. JMJD5/7 function as endopeptidases that cleave histone
      tails specifically adjacent to methylated arginine residues and continue to
      degrade N-terminal residues of histones via their aminopeptidase activity. Here,
      we report structural and biochemical studies on JMJD5/7 to understand the basis
      of substrate recognition and catalysis mechanism by this JmjC subfamily.
      Recognition between these enzymes and histone substrates is specific, which is
      reflected by the binding data between enzymes and substrates. High structural
      similarity between JMJD5 and JMJD7 is reflected by the shared common substrates
      and high binding affinity. However, JMJD5 does not bind to arginine methylated
      histone tails with additional lysine acetylation while JMJD7 does not bind to
      arginine methylated histone tails with additional lysine methylation.
      Furthermore, the complex structures of JMJD5 and arginine derivatives revealed a
      Tudor domain-like binding pocket to accommodate the methylated sidechain of
      arginine, but not lysine. There also exists a glutamine close to the catalytic
      center, which may suggest a unique imidic acid mediated catalytic mechanism for
      proteolysis by JMJD5/7.

PMID- 29459674
TI  - Identification of novel prognosis-related genes associated with cancer using
      integrative network analysis.
AB  - Prognosis identifies the seriousness and the chances of survival of a cancer
      patient. However, it remains a challenge to identify the key cancer genes in
      prognostic studies. In this study, we collected 2064 genes that were related to
      prognostic studies by using gene expression measurements curated from published
      literatures. Among them, 1820 genes were associated with copy number variations
      (CNVs). The further functional enrichment on 889 genes with frequent copy number
      gains (CNGs) revealed that these genes were significantly associated with cancer
      pathways including regulation of cell cycle, cell differentiation and mitogen
      activated protein kinase (MAPK) cascade. We further conducted integrative
      analyses of CNV and their target genes expression using the data from matched
      tumour samples of The Cancer Genome Atlas (TCGA). Ultimately, 95 key prognosis
      related genes were extracted, with concordant CNG events and increased up
      regulation in at least 300 tumour samples. These genes, and the number of samples
      in which they were found, included: ACTL6A (399), ATP6V1C1 (425), EBAG9 (412),
      FADD (308), MTDH (377), and SENP5 (304). This study provides the first
      observation of CNV in prognosis-related genes across pan-cancer. The systematic
      concordance between CNG and up-regulation of gene expression in these novel
      prognosis-related genes may indicate their prognostic significance.

PMID- 29459675
TI  - c-Jun N-terminal kinase 1 defective CD4+CD25+FoxP3+ cells prolong islet allograft
      survival in diabetic mice.
AB  - CD4+CD25+FoxP3+ cells (Tregs) inhibit inflammatory immune responses to
      allografts. Here, we found that co-transplantation of allogeneic pancreatic
      islets with Tregs that are defective in c-Jun N-terminal kinase 1 (JNK1)
      signaling prolongs islet allograft survival in the liver parenchyma of chemically
      induced diabetic mice (CDM). Adoptively transferred JNK1-/- but not wild-type
      (WT) Tregs survive longer in the liver parenchyma of CDM. JNK1-/- Tregs are
      resistant to apoptosis and express anti-apoptotic molecules. JNK1-/- Tregs
      express higher levels of lymphocyte activation gene-3 molecule (LAG-3) on their
      surface and produce higher amounts of the anti-inflammatory cytokine interleukin
      (IL)-10 compared with WT Tregs. JNK1-/- Tregs inhibit liver alloimmune responses
      more efficiently than WT Tregs. JNK1-/- but not WT Tregs are able to inhibit IL
      17 and IL-21 production through enhanced LAG-3 expression and IL-10 production.
      Our study identifies a novel role of JNK1 signaling in Tregs that enhances islet
      allograft survival in the liver parenchyma of CDM.

PMID- 29459676
TI  - Genomic Variants in NEURL, GJA1 and CUX2 Significantly Increase Genetic
      Susceptibility to Atrial Fibrillation.
AB  - Atrial fibrillation (AF) is the most common arrhythmia. In 2014, two new meta
      GWAS identified 5 AF loci, including the NEURL locus, GJA1 locus, CAND2 locus,
      and TBX5 locus in the European ancestry populations and the NEURL locus and CUX2
      locus in a Japanese population. The TBX5 locus for AF was reported by us in 2013
      in the Chinese population. Here we assessed the association between AF and SNPs
      in the NEURL, GJA1, CAND2 and CUX2 loci in the Chinese Han population. We carried
      out a large case-control association study with 1,164 AF patients and 1,460
      controls. Significant allelic and genotypic associations were identified between
      NEURL variant rs6584555 and GJA1 variant rs13216675 and AF. Significant genotypic
      association was found between CUX2 SNP rs6490029 and AF. No association was found
      between CAND2 variant rs4642101 and AF, which may be due to an insufficient power
      of the sample size for rs4642101. Together with our previous findings, seven of
      fifteen AF loci (<50%) identified by GWAS in the European ancestry populations
      conferred susceptibility to AF in the Chinese population, and explained
      approximately 14.5% of AF heritability. On the other hand, two AF loci identified
      in the Japanese population were both replicated in the Chinese population.

PMID- 29459677
TI  - A CRISPR-based screen for Hedgehog signaling provides insights into ciliary
      function and ciliopathies.
AB  - Primary cilia organize Hedgehog signaling and shape embryonic development, and
      their dysregulation is the unifying cause of ciliopathies. We conducted a
      functional genomic screen for Hedgehog signaling by engineering antibiotic-based
      selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated
      gene disruption. The screen can robustly identify factors required for ciliary
      signaling with few false positives or false negatives. Characterization of hit
      genes uncovered novel components of several ciliary structures, including a
      protein complex that contains delta-tubulin and epsilon-tubulin and is required
      for centriole maintenance. The screen also provides an unbiased tool for
      classifying ciliopathies and showed that many congenital heart disorders are
      caused by loss of ciliary signaling. Collectively, our study enables a systematic
      analysis of ciliary function and of ciliopathies, and also defines a versatile
      platform for dissecting signaling pathways through CRISPR-based screening.

PMID- 29459678
TI  - Evolutionary analysis indicates that DNA alkylation damage is a byproduct of
      cytosine DNA methyltransferase activity.
AB  - Methylation at the 5 position of cytosine in DNA (5meC) is a key epigenetic mark
      in eukaryotes. Once introduced, 5meC can be maintained through DNA replication by
      the activity of 'maintenance' DNA methyltransferases (DNMTs). Despite their
      ancient origin, DNA methylation pathways differ widely across animals, such that
      5meC is either confined to transcribed genes or lost altogether in several
      lineages. We used comparative epigenomics to investigate the evolution of DNA
      methylation. Although the model nematode Caenorhabditis elegans lacks DNA
      methylation, more basal nematodes retain cytosine DNA methylation, which is
      targeted to repeat loci. We found that DNA methylation coevolved with the DNA
      alkylation repair enzyme ALKB2 across eukaryotes. In addition, we found that
      DNMTs introduced the toxic lesion 3-methylcytosine into DNA both in vitro and in
      vivo. Alkylation damage is therefore intrinsically associated with DNMT activity,
      and this may promote the loss of DNA methylation in many species.

PMID- 29459679
TI  - Meta-analysis of genome-wide association studies for cattle stature identifies
      common genes that regulate body size in mammals.
AB  - Stature is affected by many polymorphisms of small effect in humans 1 . In
      contrast, variation in dogs, even within breeds, has been suggested to be largely
      due to variants in a small number of genes2,3. Here we use data from cattle to
      compare the genetic architecture of stature to those in humans and dogs. We
      conducted a meta-analysis for stature using 58,265 cattle from 17 populations
      with 25.4 million imputed whole-genome sequence variants. Results showed that the
      genetic architecture of stature in cattle is similar to that in humans, as the
      lead variants in 163 significantly associated genomic regions (P < 5 * 10-8)
      explained at most 13.8% of the phenotypic variance. Most of these variants were
      noncoding, including variants that were also expression quantitative trait loci
      (eQTLs) and in ChIP-seq peaks. There was significant overlap in loci for stature
      with humans and dogs, suggesting that a set of common genes regulates body size
      in mammals.

PMID- 29459681
TI  - Embryonic defects induced by maternal obesity in mice derive from Stella
      insufficiency in oocytes.
AB  - Maternal obesity can impair embryo development and offspring health, yet the
      mechanisms responsible remain poorly understood. In a high-fat diet (HFD)-based
      female mouse model of obesity, we identified a marked reduction of Stella (also
      known as DPPA3 or PGC7) protein in oocytes. Starting with this clue, we found
      that the establishment of pronuclear epigenetic asymmetry in zygotes from obese
      mice was severely disrupted, inducing the accumulation of maternal 5
      hydroxymethylcytosine modifications and DNA lesions. Furthermore, methylome-wide
      sequencing analysis detected global hypomethylation across the zygote genome in
      HFD-fed mice, with a specific enrichment in transposon elements and unique
      regions. Notably, overexpression of Stella in the oocytes of HFD-fed mice not
      only restored the epigenetic remodeling in zygotes but also partly ameliorated
      the maternal-obesity-associated developmental defects in early embryos and fetal
      growth. Thus, Stella insufficiency in oocytes may represent a critical mechanism
      that mediates the phenotypic effects of maternal obesity in embryos and
      offspring.

PMID- 29459680
TI  - Genome-wide mapping of global-to-local genetic effects on human facial shape.
AB  - Genome-wide association scans of complex multipartite traits like the human face
      typically use preselected phenotypic measures. Here we report a data-driven
      approach to phenotyping facial shape at multiple levels of organization, allowing
      for an open-ended description of facial variation while preserving statistical
      power. In a sample of 2,329 persons of European ancestry, we identified 38 loci,
      15 of which replicated in an independent European sample (n = 1,719). Four loci
      were completely new. For the others, additional support (n = 9) or pleiotropic
      effects (n = 2) were found in the literature, but the results reported here were
      further refined. All 15 replicated loci highlighted distinctive patterns of
      global-to-local genetic effects on facial shape and showed enrichment for active
      chromatin elements in human cranial neural crest cells, suggesting an early
      developmental origin of the facial variation captured. These results have
      implications for studies of facial genetics and other complex morphological
      traits.

PMID- 29459682
TI  - Oxidative demethylation of algal carbohydrates by cytochrome P450 monooxygenases.
AB  - Sugar O-methylation shields algal polysaccharides against microbial hydrolytic
      enzymes. Here, we describe cytochrome P450 monooxygenases from marine bacteria
      that, together with appropriate redox-partner proteins, catalyze the oxidative
      demethylation of 6-O-methyl-D-galactose, which is an abundant monosaccharide of
      the algal polysaccharides agarose and porphyran. This previously unknown
      biological function extends the group of carbohydrate-active enzymes to include
      the class of cytochrome P450 monooxygenases.

PMID- 29459683
TI  - Nano-Architecture of nitrogen-doped graphene films synthesized from a solid CN
      source.
AB  - New synthesis routes to tailor graphene properties by controlling the
      concentration and chemical configuration of dopants show great promise. Herein we
      report the direct reproducible synthesis of 2-3% nitrogen-doped 'few-layer'
      graphene from a solid state nitrogen carbide a-C:N source synthesized by
      femtosecond pulsed laser ablation. Analytical investigations, including
      synchrotron facilities, made it possible to identify the configuration and
      chemistry of the nitrogen-doped graphene films. Auger mapping successfully
      quantified the 2D distribution of the number of graphene layers over the surface,
      and hence offers a new original way to probe the architecture of graphene sheets.
      The films mainly consist in a Bernal ABA stacking three-layer architecture, with
      a layer number distribution ranging from 2 to 6. Nitrogen doping affects the
      charge carrier distribution but has no significant effects on the number of
      lattice defects or disorders, compared to undoped graphene synthetized in similar
      conditions. Pyridinic, quaternary and pyrrolic nitrogen are the dominant chemical
      configurations, pyridinic N being preponderant at the scale of the film
      architecture. This work opens highly promising perspectives for the development
      of self-organized nitrogen-doped graphene materials, as synthetized from solid
      carbon nitride, with various functionalities, and for the characterization of 2D
      materials using a significant new methodology.

PMID- 29459685
TI  - Reversible 90-Degree Rotation of Fe Magnetic Moment Using Hydrogen.
AB  - [Pd/Fe]2 multilayers were deposited on a flat MgO(001) to study the effect of
      hydrogen on magnetic interlayer coupling. Complex magnetic hysteresis behavior,
      including single, double, and triple loops, were measured as a function of the
      azimuthal angle in a longitudinal and transverse direction. With a combination of
      a 2-fold magnetic anisotropy energy (MAE) in the bottom-Fe and a 4-fold MAE in
      the top-Fe, the complex magnetic hysteresis behavior could be clearly explained.
      Two well-split hysteresis loops with almost zero Kerr remanence were measured by
      choosing a suitable Pd thickness and applying the magnetic field perpendicular to
      the easy axis of the bottom-Fe. The split double loops originated from the 90
      degrees -rotation of the top-Fe moment. On exposure to a hydrogen gas atmosphere,
      the separation of the two minor loops increased, indicating that Pd-hydride
      formation enhanced the ferromagnetic coupling between the two Fe layers. Based on
      these observations, we proposed that, by applying a suitable constant magnetic
      field, the top-Fe moment could undergo reversible 90 degrees -rotation following
      hydrogen exposure. The results suggest that the Pd space layer used for mediating
      the magnetic interlayer coupling is sensitive to hydrogen, and therefore, the
      multilayer system can function as a giant magnetoresistance-type sensor suitable
      for hydrogen gas.

PMID- 29459684
TI  - Clinical analysis of peri-operative hidden blood loss of elderly patients with
      intertrochanteric fractures treated by unreamed proximal femoral nail anti
      rotation.
AB  - The purpose of this study was to quantify the peri-operative blood loss of
      elderly patients with intertrochanteric fractures treated by unreamed proximal
      femoral nail anti-rotation (PFNA) and analyze whether the substantial hidden
      blood loss was induced by initial trauma or the operation. The clinical data of
      123 patients with intertrochanteric fracture treated with unreamed PFNA from Jan
      2013 to Apr 2017 were analyzed retrospectively. Blood routine on admission day
      (ADM), pre-operative day one (PRE), post-operative days one and three (POD1 and
      POD3) and the visible blood loss (VBL) were obtained. The total blood loss (TBL)
      from ADM to POD1 and POD3 were 693.5 +/- 359.6 ml and 863.8 +/- 429.9 ml, of
      which the corresponding hidden blood loss (HBL) was 86.8% and 89.4% respectively.
      The mean TBL and HBL from ADM to PRE (375.5 +/- 242.0 ml, 375.5 +/- 242.0 ml)
      were higher than that from PRE to POD1 (318.0 +/- 183.4 ml, 226.5 +/- 163.2 ml),
      p < 0.001 respectively. There was no significant difference between HBL from ADM
      to PRE and HBL from PRE to POD3 (375.5 +/- 242.0 ml, 396.7 +/- 254.0 ml, p =
      0.361). The majority of peri-operative HBL occurred before surgery, it was mainly
      associated with the initial trauma rather than the operation.

PMID- 29459686
TI  - Long noncoding RNA Gomafu upregulates Foxo1 expression to promote hepatic insulin
      resistance by sponging miR-139-5p.
AB  - Long non-coding RNA Gomafu is involved in diabetes-related diseases. However, its
      role in insulin resistance (IR) remains unclear. Our objective is to explore the
      role of Gomafu in hepatic IR and glucose intolerance. Gomafu expression was
      determined in livers of ob/ob mice and high-fat diet (HFD) mice. The binding
      activity of NF-kappaB on the Gomafu promoter was measured by chromatin
      immunoprecipitation and quantitative real-time PCR assays. Increased Gomafu
      expression was observed in the livers of obese mice. Besides, the binding of NF
      kappaB on the Gomafu promoter was also observed in hepatocytes from ob/ob mice.
      Further study showed that knockdown of NF-kappaB p65 alleviated the increase in
      hepatic Gomafu expression in vivo and in vitro. Knockdown of hepatic Gomafu
      inhibited hepatic glucose production (HGP) and improved insulin sensitivity in
      obese mice, whereas, overexpression of hepatic Gomafu resulted in an increase in
      random and fasting blood glucose levels in lean mice. In addition, we
      demonstrated that Gomafu functioned as miR-139 sponge and led to the de
      repression of its target gene Foxo1, which played an important role in
      gluconeogenesis and HGP in hepatocytes. Finally, silenced Foxo1 expression
      abolished the effect of Gomafu overexpression on gluconeogenesis and glucose
      production in hepatocytes. Taken together, our data suggested that the increase
      in Gomafu expression contributed to hepatic IR in obese mice.

PMID- 29459687
TI  - Maturation State and Matrix Microstructure Regulate Interstitial Cell Migration
      in Dense Connective Tissues.
AB  - Few regenerative approaches exist for the treatment of injuries to adult dense
      connective tissues. Compared to fetal tissues, adult connective tissues are
      hypocellular and show limited healing after injury. We hypothesized that robust
      repair can occur in fetal tissues with an immature extracellular matrix (ECM)
      that is conducive to cell migration, and that this process fails in adults due to
      the biophysical barriers imposed by the mature ECM. Using the knee meniscus as a
      platform, we evaluated the evolving micromechanics and microstructure of fetal
      and adult tissues, and interrogated the interstitial migratory capacity of adult
      meniscal cells through fetal and adult tissue microenvironments with or without
      partial enzymatic digestion. To integrate our findings, a computational model was
      implemented to determine how changing biophysical parameters impact cell
      migration through these dense networks. Our results show that the micromechanics
      and microstructure of the adult meniscus ECM sterically hinder cell mobility, and
      that modulation of these ECM attributes via an exogenous matrix-degrading enzyme
      permits migration through this otherwise impenetrable network. By addressing the
      inherent limitations to repair imposed by the mature ECM, these studies may
      define new clinical strategies to promote repair of damaged dense connective
      tissues in adults.

PMID- 29459688
TI  - iTRAQ-based quantitative proteomic analysis reveals important metabolic pathways
      for arsenic-induced liver fibrosis in rats.
AB  - Long-term consumption of sodium arsenite contaminated water can cause endemic
      arsenic disease. The proteome profile changes of liver fibrosis after exposure to
      arsenite containing water remain unclear. In this study, Sprague-Dawley (SD) male
      rats were treated with sodium arsenite (iAs3+), using a daily dose of 1.36 mg/kg
      body weight (medium dose group, M), 2.73 mg/kg body weight (high dose group, H)
      or deionized water (control group, C). Isobaric tags for relative and absolute
      quantitation (iTRAQ) were used to identify the different abundant proteins (DAPs)
      after arsenic-induced liver fibrosis. A total of 2987 high-quality proteins were
      detected (95% confident peptides >= 2), 608 of which were differentially
      expressed (fold change > 2 and p < 0.05) in M group and 475 in H group. Moreover,
      431 DAPs were found in both M and H groups and used in subsequent bioinformatic
      analyses. Gene ontology (GO) analysis revealed 4,709 GO terms could be mapped,
      among which purine binding, actin filament binding and protein kinase binding
      were the most enriched terms for molecular function category. In addition,
      protein-protein interaction analysis showed six clusters of interaction networks.
      Our data provided new insights into the proteome changes after arsenic-induced
      liver fibrosis in model rats.

PMID- 29459689
TI  - The value of hip circumference/heightx ratio for identifying childhood
      hypertension.
AB  - To investigate the value of hip circumference related indexes for identifying
      childhood hypertension. In 2011, 1,352 Han children aged 7-12 years were
      recruited in our study. Hypertension was defined as systolic blood pressure or
      diastolic blood pressure >=95th percentile for all three screenings. We set the
      power value of the hip circumference/heightx ratio (x = 0, 0.8, 1 and 1.5) and
      studied the association with blood pressure. Hip circumference, hip
      circumference/height0.8, hip circumference/height and hip circumference/height1.5
      all showed a positive correlation with systolic blood pressure and diastolic
      blood pressure(P < 0.05). Area under the curve (AUC) was used to evaluate the
      abilities of hip circumference related indexes. Hip circumference/height0.8, hip
      circumference/height and hip circumference/height1.5 were not superior to hip
      circumference. The present study demonstrates that hip circumference measurement
      is a helpful tool to detect the presence of hypertension in Han children 7-12
      years old.

PMID- 29459690
TI  - Scattering resonances in bimolecular collisions between NO radicals and H2
      challenge the theoretical gold standard.
AB  - Over the last 25 years, the formalism known as coupled-cluster (CC) theory has
      emerged as the method of choice for the ab initio calculation of intermolecular
      interaction potentials. The implementation known as CCSD(T) is often referred to
      as the gold standard in quantum chemistry. It gives excellent agreement with
      experimental observations for a variety of energy-transfer processes in molecular
      collisions, and it is used to calibrate density functional theory. Here, we
      present measurements of low-energy collisions between NO radicals and H2
      molecules with a resolution that challenges the most sophisticated quantum
      chemistry calculations at the CCSD(T) level. Using hitherto-unexplored anti
      seeding techniques to reduce the collision energy in a crossed-beam inelastic
      scattering experiment, a resonance structure near 14 cm-1 is clearly resolved in
      the state-to-state integral cross-section, and a unique resonance fingerprint is
      observed in the corresponding differential cross-section. This resonance
      structure discriminates between two NO-H2 potentials calculated at the CCSD(T)
      level and pushes the required accuracy beyond the gold standard.

PMID- 29459691
TI  - Observation of correlated excitations in bimolecular collisions.
AB  - Although collisions between atoms and molecules are largely understood,
      collisions between two molecules have proven much harder to study. In both
      experiment and theory, our ability to determine quantum-state-resolved
      bimolecular cross-sections lags behind their atom-molecule counterparts by
      decades. For many bimolecular systems, even rules of thumb-much less intuitive
      understanding-of scattering cross sections are lacking. Here, we report the
      measurement of state-to-state differential cross sections on the collision of
      state-selected and velocity-controlled nitric oxide (NO) radicals and oxygen (O2)
      molecules. Using velocity map imaging of the scattered NO radicals, the full
      product-pair correlations of rotational excitation that occurs in both collision
      partners from individual encounters are revealed. The correlated cross sections
      show surprisingly good agreement with quantum scattering calculations using ab
      initio NO-O2 potential energy surfaces. The observations show that the well-known
      energy-gap law that governs atom-molecule collisions does not generally apply to
      bimolecular excitation processes, and reveal a propensity rule for the vector
      correlation of product angular momenta.

PMID- 29459692
TI  - Isolation of uracil auxotroph mutants of coral symbiont alga for symbiosis
      studies.
AB  - Coral reef ecosystems rely on stable symbiotic relationship between the
      dinoflagellate Symbiodinium spp. and host cnidarian animals. The collapse of such
      symbiosis could cause coral 'bleaching' and subsequent host death. Despite huge
      interest on Symbiodinium, lack of mutant strains and readily available genetic
      tools have hampered molecular research. A major issue was the tolerance to marker
      antibiotics. Here, we isolated Symbiodinium mutants requiring uracil for growth,
      and hence, useful in transformation screening. We cultured Symbiodinium spp.
      cells in the presence of 5-fluoroorotic acid (5FOA), which inhibits the growth of
      cells expressing URA3 encoding orotidine-5'-monophosphate decarboxylase, and
      isolated cells that require uracil for growth. Sequence analyses and genetic
      complementation tests using yeast demonstrated that one of the mutant cell lines
      had a point mutation in URA3, resulting in a splicing error at an unusual exon
      intron junction, and consequently, loss of enzyme activity. This mutant could
      maintain a symbiotic relationship with the model sea anemone Exaiptasia pallida
      only in sea water containing uracil. Results show that the URA3 mutant will be a
      useful tool for screening Symbiodinium transformants, both ex and in hospite, as
      survival in the absence of uracil is possible only upon successful introduction
      of URA3.

PMID- 29459693
TI  - Identification and characterization of SSE15206, a microtubule depolymerizing
      agent that overcomes multidrug resistance.
AB  - Microtubules are highly dynamic structures that form spindle fibres during
      mitosis and are one of the most validated cancer targets. The success of drugs
      targeting microtubules, however, is often limited by the development of multidrug
      resistance. Here we describe the discovery and characterization of SSE15206, a
      pyrazolinethioamide derivative [3-phenyl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro
      1H-pyrazole-1-carbothioamide] that has potent antiproliferative activities in
      cancer cell lines of different origins and overcomes resistance to microtubule
      targeting agents. Treatment of cells with SSE15206 causes aberrant mitosis
      resulting in G2/M arrest due to incomplete spindle formation, a phenotype often
      associated with drugs that interfere with microtubule dynamics. SSE15206 inhibits
      microtubule polymerization both in biochemical and cellular assays by binding to
      colchicine site in tubulin as shown by docking and competition studies. Prolonged
      treatment of cells with the compound results in apoptotic cell death [increased
      Poly (ADP-ribose) polymerase cleavage and Annexin V/PI staining] accompanied by
      p53 induction. More importantly, we demonstrate that SSE15206 is able to overcome
      resistance to chemotherapeutic drugs in different cancer cell lines including
      multidrug-resistant KB-V1 and A2780-Pac-Res cell lines overexpressing MDR-1,
      making it a promising hit for the lead optimization studies to target multidrug
      resistance.

PMID- 29459694
TI  - Human antibody responses against non-covalently cell wall-bound Staphylococcus
      aureus proteins.
AB  - Human antibody responses to pathogens, like Staphylococcus aureus, are important
      indicators for in vivo expression and immunogenicity of particular bacterial
      components. Accordingly, comparing the antibody responses to S. aureus components
      may serve to predict their potential applicability as antigens for vaccination.
      The present study was aimed at assessing immunoglobulin G (IgG) responses
      elicited by non-covalently cell surface-bound proteins of S. aureus, which thus
      far received relatively little attention. To this end, we applied plasma samples
      from patients with the genetic blistering disease epidermolysis bullosa (EB) and
      healthy S. aureus carriers. Of note, wounds of EB patients are highly colonized
      with S. aureus and accordingly these patients are more seriously exposed to
      staphylococcal antigens than healthy individuals. Ten non-covalently cell surface
      bound proteins of S. aureus, namely Atl, Eap, Efb, EMP, IsaA, LukG, LukH, SA0710,
      Sle1 and SsaA2, were selected by bioinformatics and biochemical approaches. These
      antigens were recombinantly expressed, purified and tested for specific IgG
      responses using human plasma. We show that high exposure of EB patients to S.
      aureus is mirrored by elevated IgG levels against all tested non-covalently cell
      wall-bound staphylococcal antigens. This implies that these S. aureus cell
      surface proteins are prime targets for the human immune system.

PMID- 29459695
TI  - Light action spectrum on oxidative stress and mitochondrial damage in A2E-loaded
      retinal pigment epithelium cells.
AB  - AIMS: Blue light is an identified risk factor for age-related macular
      degeneration (AMD). We investigated oxidative stress markers and mitochondrial
      changes in A2E-loaded retinal pigment epithelium cells under the blue-green part
      of the solar spectrum that reaches the retina to better understand the mechanisms
      underlying light-elicited toxicity. RESULTS: Primary retinal pigment epithelium
      cells were loaded with a retinal photosensitizer, AE2, to mimic aging. Using a
      custom-made illumination device that delivers 10 nm-wide light bands, we
      demonstrated that A2E-loaded RPE cells generated high levels of both hydrogen
      peroxide (H2O2) and superoxide anion (O2*-) when exposed to blue-violet light. In
      addition, they exhibited perinuclear clustering of mitochondria with a decrease
      of both their mitochondrial membrane potential and their respiratory activities.
      The increase of oxidative stress resulted in increased levels of the oxidized
      form of glutathione and decreased superoxide dismutase (SOD) and catalase
      activities. Furthermore, mRNA expression levels of the main antioxidant enzymes
      (SOD2, catalase, and GPX1) also decreased. CONCLUSIONS: Using an innovative
      illumination device, we measured the precise action spectrum of the oxidative
      stress mechanisms on A2E-loaded retinal pigment epithelium cells. We defined 415
      455 nm blue-violet light, within the solar spectrum reaching the retina, to be
      the spectral band that generates the highest amount of reactive oxygen species
      and produces the highest level of mitochondrial dysfunction, explaining its toxic
      effect. This study further highlights the need to filter these wavelengths from
      the eyes of AMD patients.

PMID- 29459696
TI  - Null Model and Community Structure in Multiplex Networks.
AB  - The multiple relationships among objects in complex systems can be described well
      by multiplex networks, which contain rich information of the connections between
      objects. The null model of networks, which can be used to quantify the specific
      nature of a network, is a powerful tool for analysing the structural
      characteristics of complex systems. However, the null model for multiplex
      networks remains largely unexplored. In this paper, we propose a null model for
      multiplex networks based on the node redundancy degree, which is a natural
      measure for describing the multiple relationships in multiplex networks. Based on
      this model, we define the modularity of multiplex networks to study the community
      structures in multiplex networks and demonstrate our theory in practice through
      community detection in four real-world networks. The results show that our model
      can reveal the community structures in multiplex networks and indicate that our
      null model is a useful approach for providing new insights into the specific
      nature of multiplex networks, which are difficult to quantify.

PMID- 29459698
TI  - Identification of a locus conferring dominant resistance to maize rough dwarf
      disease in maize.
AB  - Maize rough dwarf disease (MRDD) is a severe viral disease of maize that occurs
      worldwide, particularly in the summer maize-growing areas in China, resulting in
      yield losses and quality deterioration in susceptible maize varieties. An
      effective solution to control MRDD is to use resistance genes to improve the
      behavior of susceptible genotypes. Here, we employed maize F2 populations derived
      from a cross between susceptible line S221 and resistant line K36 for the deep
      sequencing of the two DNA pools containing extremely resistant and susceptible F2
      individuals, and used traditional linkage analysis to locate the resistance
      related genomic region. The results showed that MRDD resistance in K36 was
      controlled by a single dominant locus, and an associated region was identified
      within the genomic interval of 68,396,487 bp and 69,523,478 bp on chromosome 6.
      Two simple sequence repeat (SSR) markers 6F29R29 and 6F34R34 were tightly linked
      to the MRDD resistance locus. The findings of the present study improve our
      understanding of the inheritance patterns of MRDD resistance, and should inform
      MRDD-resistant maize breeding programs.

PMID- 29459697
TI  - Serum Metabolomics of Activity Energy Expenditure and its Relation to Metabolic
      Syndrome and Obesity.
AB  - Modifiable lifestyle factors, including exercise and activity energy expenditure
      (AEE), may attenuate the unfavorable health effects of obesity, such as risk
      factors of metabolic syndrome (MetS). However, the underlying mechanisms are not
      clear. In this study we sought to investigate whether the metabolite profiles of
      MetS and adiposity assessed by body mass index (BMI) and central obesity are
      inversely correlated with AEE and physical activity. We studied 35 men and 47
      women, aged 30-60 years, using doubly labeled water to derive AEE and the
      Sedentary Time and Activity Reporting Questionnaire (STAR-Q) to determine the
      time spent in moderate and vigorous physical activity. Proton nuclear magnetic
      resonance spectroscopy was used for serum metabolomics analysis. Serine and
      glycine were found in lower concentrations in participants with more MetS risk
      factors and greater adiposity. However, serine and glycine concentrations were
      higher with increasing activity measures. Metabolic pathway analysis and recent
      literature suggests that the lower serine and glycine concentrations in the
      overweight/obese state could be a consequence of serine entering de novo
      sphingolipid synthesis. Taken together, higher levels of AEE and physical
      activity may play a crucial part in improving metabolic health in men and women
      with and without MetS risk factors.

PMID- 29459699
TI  - Homogenization and impoverishment of taxonomic and functional diversity of ants
      in Eucalyptus plantations.
AB  - Despite its negative impacts on the environment and biodiversity, tree
      plantations can contribute to biodiversity conservation in fragmented landscapes,
      as they harbor many native species. In this study, we investigated the impact of
      Eucalyptus plantations on the taxonomic and functional diversity of ant
      communities, comparing ant communities sampled in managed and unmanaged
      (abandoned for 28 years) Eucalyptus plantations, and native Atlantic rain
      forests. Eucalyptus plantations, both managed and unmanaged, reduced the
      functional diversity and increased the similarity between ant communities leading
      to functional homogenization. While communities in managed plantations had the
      lowest values of both taxonomic and functional ant diversities, ant communities
      from unmanaged plantations had similar values of species richness, functional
      redundancy and Rao's Q compared to ant communities from forest patches (although
      functional richness was lower). In addition, communities in unmanaged Eucalyptus
      plantations were taxonomically and functionally more similar to communities
      located in managed plantations, indicating that Eucalyptus plantations have a
      severe long-term impact on ant communities. These results indicate that natural
      regeneration may mitigate the impact of Eucalyptus management, particularly
      regarding the functional structure of the community (alpha diversity), although
      it does not attenuate the effects of long term homogenization in community
      composition (beta diversity).

PMID- 29459700
TI  - Split spawning realigns coral reproduction with optimal environmental windows.
AB  - Split spawning in coral populations occurs when gamete maturation and mass
      spawning are split over two consecutive months. While split spawning has been
      observed at many reefs, little is known about the frequency and significance of
      these events. Here we show that split spawning occurred frequently and
      predictably over a decade at Scott Reef. Split spawning overlays the biannual
      spawning pattern in the region and occurs when the full moon falls in the first
      week of the usual spawning month, or the last week of the previous month.
      Additionally, in split years most species have their main spawning event after a
      13-month lunar cycle, in the month following the usual spawning month. Without
      split spawning, spawn dates would shift by ~10 days each year to occur outside of
      optimal environmental windows. Our results suggest that split spawning is driven
      by a disconnect between lunar and seasonal cues, and is analogous with a 'leap
      year' in coral reproduction, realigning spawning dates with favourable conditions
      for reproduction.

PMID- 29459702
TI  - QFMatch: multidimensional flow and mass cytometry samples alignment.
AB  - Part of the flow/mass cytometry data analysis process is aligning (matching) cell
      subsets between relevant samples. Current methods address this cluster-matching
      problem in ways that are either computationally expensive, affected by the curse
      of dimensionality, or fail when population patterns significantly vary between
      samples. Here, we introduce a quadratic form (QF)-based cluster matching
      algorithm (QFMatch) that is computationally efficient and accommodates cases
      where population locations differ significantly (or even disappear or appear)
      from sample to sample. We demonstrate the effectiveness of QFMatch by evaluating
      sample datasets from immunology studies. The algorithm is based on a novel
      multivariate extension of the quadratic form distance for the comparison of flow
      cytometry data sets. We show that this QF distance has attractive computational
      and statistical properties that make it well suited for analysis tasks that
      involve the comparison of flow/mass cytometry samples.

PMID- 29459701
TI  - Imaging of electrical activity in small diameter fibers of the murine peripheral
      nerve with virally-delivered GCaMP6f.
AB  - Current neural interfaces are hampered by lack of specificity and selectivity for
      neural interrogation. A method that might improve these interfaces is an optical
      peripheral nerve interface which communicates with individual axons via
      optogenetic reporters. To determine the feasibility of such an interface, we
      delivered the genetically encoded calcium indicator GCaMP6f to the mouse
      peripheral nerve by intramuscular injection of adenoassociated viral vector
      (AAV1) under the control of the CAG (chicken beta actin- cytomegalovirus hybrid
      promoter). Small diameter axons in the common peroneal nerve were transduced and
      demonstrated electrically inducible calcium transients ex vivo. Responses to
      single electrical stimuli were resolvable, and increasing the number of stimuli
      resulted in a monotonic increase in maximum fluorescence and a prolongation of
      calcium transient kinetics. This work demonstrates the viability of using a
      virally-delivered, genetically-encoded calcium indicator to read-out from
      peripheral nerve axons.

PMID- 29459703
TI  - Investigation on the role of surfactants in bubble-algae interaction in flotation
      harvesting of Chlorella vulgaris.
AB  - In this work, a fundamental study was carried out on the role of surfactants in
      bubble-algae interaction to improve the understanding of how surfactants
      influence the flotation performance. Flotation tests for harvesting Chlorella
      vulgaris were first conducted using two surfactants, hexadecyltrimethyl ammonium
      bromide (C16TAB) and tea saponin. The effect of surfactants on harvesting
      efficiency was found to depend on their type and concentration. The present
      results also indicated that C16TAB exhibited higher harvesting efficiency than
      tea saponin. The adsorption experiments of surfactants onto C. vulgaris and the
      characterization measurements of algae surface were then carried out to reveal
      underlying interaction mechanisms between surfactants and algae in air flotation
      process. The results confirmed the adsorption process of surfactants onto C.
      vulgaris was feasible, spontaneous and endothermic. Subsequently, two mechanism
      models were proposed to qualitatively establish the interaction relationship
      among algae, surfactants and bubbles in the flotation. According to two models,
      C16TAB could neutralize the algal potential, while tea saponin converted algal
      surface from hydrophilic into hydrophobic. Overall, two surfactants used here
      could facilitate attachment of C. vulgaris onto bubbles, making the algae easier
      to be harvested, thereby increasing the flotation recovery.

PMID- 29459704
TI  - Initial meconium microbiome in Chinese neonates delivered naturally or by
      cesarean section.
AB  - Previous studies have revealed significant differences in microbiome compositions
      between infants delivered via cesarean section (C-section) and natural vaginal
      birth. However, the importance of the delivery mode in the first days of life
      remains unclear. Importantly, this stage is minimally affected by infant feeding.
      Here, we used a metagenomic sequencing technique to characterize the meconium
      microbiome from the feces of a Chinese cohort of vaginally and C-section
      delivered infants, including in vitro fertilization (IVF) newborns, during the
      first 24 h after birth. Meconium microbiome diversity was higher in vaginally
      delivered infants than that in C-section-delivered infants. Propionibacterium
      species were most abundant in the vaginally delivered infants, whereas the C
      section group had high levels of Bacillus licheniformis. The two IVF newborns
      delivered by C-section harbored microbial communities similar to the vaginal
      microbiome in terms of taxonomic composition. Metabolic functions of the C
      section group suffered more from the influence of the dominant group (B.
      licheniformis), whereas the vaginal group was more homogeneous, with a metabolism
      dominated by multi-microbes. Moreover, different modes of delivery affected the
      antibiotic resistance gene (ARG) prevalence. These findings provide novel
      information for the development of strategies to guide a healthy mode of delivery
      and promote the formation of healthy microbiota.

PMID- 29459705
TI  - Duplication resolves conflict.

PMID- 29459706
TI  - Gene-based predictive models of trophic modes suggest Asgard archaea are not
      phagocytotic.
AB  - With the current explosion of genomic data, there is a greater need to draw
      inference on phenotypic information based on DNA sequence alone. We considered
      complete genomes from 35 diverse eukaryotic lineages, and discovered sets of
      proteins predictive of trophic mode, including a set of 485 proteins that are
      enriched among phagocytotic eukaryotes (organisms that internalize large
      particles). Our model is also predictive of other aspects of trophic mode,
      including photosynthesis and the ability to synthesize a set of organic compounds
      needed for growth (prototrophy for those molecules). We applied our model to the
      Asgard archaea, a group of uncultured microorganisms that show close affinities
      to eukaryotes, to test whether the organisms are capable of phagocytosis, a
      phenotypic trait often considered a prerequisite for mitochondrial acquisition.
      Our analyses suggest that members of the Asgard archaea-despite having some
      eukaryote-specific protein families not found in other prokaryotes-do not use
      phagocytosis. Moreover, our data suggest that the process of phagocytosis arose
      from a combination of both archaeal and bacterial components, but also required
      additional eukaryote-specific innovations.

PMID- 29459708
TI  - Patterns of shared signatures of recent positive selection across human
      populations.
AB  - Signatures of recent positive selection often overlap across human populations,
      but the question of how often these overlaps represent a single ancestral event
      remains unresolved. If a single selective event spread across many populations,
      the same sweeping haplotype should appear in each population and the selective
      pressure could be common across populations and environments. Identifying such
      shared selective events could identify genomic loci and human traits important in
      recent history across the globe. In addition, genomic annotations that recently
      became available could help attach these signatures to a potential gene and
      molecular phenotype selected across populations. Here, we present a catalogue of
      selective sweeps in humans, and identify those that overlap and share a sweeping
      haplotype. We connect these sweep overlaps with potential biological mechanisms
      at several loci, including potential new sites of adaptive introgression, the
      glycophorin locus associated with malarial resistance and the alcohol
      dehydrogenase cluster associated with alcohol dependency.

PMID- 29459707
TI  - Hologenomic adaptations underlying the evolution of sanguivory in the common
      vampire bat.
AB  - Adaptation to specialized diets often requires modifications at both genomic and
      microbiome levels. We applied a hologenomic approach to the common vampire bat
      (Desmodus rotundus), one of the only three obligate blood-feeding (sanguivorous)
      mammals, to study the evolution of its complex dietary adaptation. Specifically,
      we assembled its high-quality reference genome (scaffold N50 = 26.9 Mb, contig
      N50 = 36.6 kb) and gut metagenome, and compared them against those of
      insectivorous, frugivorous and carnivorous bats. Our analyses showed a particular
      common vampire bat genomic landscape regarding integrated viral elements, a
      dietary and phylogenetic influence on gut microbiome taxonomic and functional
      profiles, and that both genetic elements harbour key traits related to the
      nutritional (for example, vitamin and lipid shortage) and non-nutritional (for
      example, nitrogen waste and osmotic homeostasis) challenges of sanguivory. These
      findings highlight the value of a holistic study of both the host and its
      microbiota when attempting to decipher adaptations underlying radical dietary
      lifestyles.

PMID- 29459710
TI  - Lack of support for adaptation of post-glacial horses to woodlands.

PMID- 29459709
TI  - Gene duplicates resolving sexual conflict rapidly evolved essential gametogenesis
      functions.
AB  - Males and females have different fitness optima but share the vast majority of
      their genomes, causing an inherent genetic conflict between the two sexes that
      must be resolved to achieve maximal population fitness. We show that two tandem
      duplicate genes found specifically in Drosophila melanogaster are sexually
      antagonistic, but rapidly evolved sex-specific functions and expression patterns
      that mitigate their antagonistic effects. We use copy-specific knockouts and
      rescue experiments to show that Apollo (Apl) is essential for male fertility but
      detrimental to female fertility, in addition to its important role in
      development, while Artemis (Arts) is essential for female fertility but
      detrimental to male fertility. Further analyses show that Apl and Arts have
      essential roles in spermatogenesis and oogenesis. These duplicates formed
      ~200,000 years ago, underwent a strong selective sweep and lost most expression
      in the antagonized sex. These data provide direct evidence that gene duplication
      allowed rapid mitigation of sexual conflict by allowing Apl and Arts to evolve
      essential sex-specific reproductive functions and complementary expression in
      male and female gonads.

PMID- 29459711
TI  - Broadband terahertz absorber based on multi-band continuous plasmon resonances in
      geometrically gradient dielectric-loaded graphene plasmon structure.
AB  - We propose a broadband terahertz absorber consisting of nonstructured graphene
      loaded with arrays of elliptic dielectric cylinders. The relative bandwidth for
      the absorption above 90% reaches about 65%. The working mechanism of broad
      bandwidth mainly comes from two aspects. One is that the nonstructured graphene
      loaded with elliptic dielectric cylinders provides multiple discrete graphene
      plasmon resonances with large relative frequency interval. The other is that, for
      each discrete resonance, there exists a set of continuous plasmon resonances
      because the width of the dielectric structure varies continuously and gradiently.
      The broadband terahertz absorber we demonstrate here, based on geometrically
      gradient dielectric structures and nonstructured graphene, avoids the graphene
      processing, which shows great potential applications in related devices.

PMID- 29459712
TI  - The E3 ubiquitin ligase Triad1 influences development of Mll-Ell-induced acute
      myeloid leukemia.
AB  - Chromosomal translocations involving the MLL1 gene characterize a poor prognosis
      subset of acute myeloid leukemia (AML), referred to as 11q23-AML. Transcription
      of the HOXA9 and HOXA10 genes is enhanced in hematopoietic stem and progenitor
      cells in these leukemias. We previously found the ARIH2 gene was repressed by
      HoxA9 in myeloid progenitors, but activated by HoxA10 during granulopoiesis.
      ARIH2 encodes the Triad1 protein, an anti-proliferative E3 ubiquitin ligase. In
      the current study, we investigate the role of Triad1 in leukemogenesis induced by
      an MLL1 fusion protein (Mll-Ell). We found Mll-Ell increased expression of HoxA9,
      HoxA10, and Triad1 because HoxA9 represses only one of two ARIH2 cis elements
      that are activated by HoxA10. Although Triad1 antagonized the generally pro
      proliferative effects of the Mll-Ell oncoprotein, we found blocking HoxA9 and
      HoxA10 phosphorylation shifted the balance to ARIH2 repression in Mll-Ell+ cells.
      We investigated the significance of these in vitro results in a murine bone
      marrow transplant model. We found Triad1 knockdown significantly shortened the
      latency to development of AML in mice transplanted with Mll-Ell-transduced bone
      marrow. And, Triad1 expression fell during the prolonged AML latency period in
      mice transplanted with bone marrow expressing Mll-Ell alone. Our studies identify
      Triad1 as a leukemia suppressor in 11q23-AML. This suggests defining relevant
      Triad1 substrates may indicate novel therapeutic targets in this disease.

PMID- 29459713
TI  - Elevated mitochondrial SLC25A29 in cancer modulates metabolic status by
      increasing mitochondria-derived nitric oxide.
AB  - Warburg effect has been recognized as a hallmark of cancer cells for many years,
      but its modulation mechanism remains a great focus. Our current study found a
      member of solute carrier family 25 (SLC25A29), the main arginine transporter on
      mitochondria, significantly elevated in various cancer cells. Knockout of
      SLC25A29 by CRISPR/Cas9 inhibited proliferation and migration of cancer cells
      both in vitro and in vivo. SLC25A29-knockout cells also showed an altered
      metabolic status with enhanced mitochondrial respiration and reduced glycolysis.
      All of above impacts could be reversed after rescuing SLC25A29 expression in
      SLC25A29-knockout cells. Arginine is transported into mitochondria partly for
      nitric oxide (NO) synthesis. Deletion of SLC25A29 resulted in severe decrease of
      NO production, indicating that the mitochondria is a significant source of NO.
      SLC25A29-knockout cells dramatically altered the variation of metabolic
      processes, whereas addition of arginine failed to reverse the effect,
      highlighting the necessity of transporting arginine into mitochondria by
      SLC25A29. In conclusion, aberrant elevated SLC25A29 in cancer functioned to
      transport more arginine into mitochondria, improved mitochondria-derived NO
      levels, thus modulated metabolic status to facilitate increased cancer
      progression.

PMID- 29459715
TI  - Saliva as a medium to detect and measure biomarkers related to pain.
AB  - Saliva is often neglected as a body fluid of diagnostic or prognostic value, even
      though generally well accepted by the patients. This is due to lack of a
      standardized collection procedure. The aim of this study was to identify the
      ideal saliva collection technique and develop new sensitive methods to detect and
      analyse markers related to pain in healthy pain-free subjects. Plasma and five
      different saliva collection approached was evaluated during strictly controlled
      conditions. Levels of nerve growth factor (NGF), calcitonin gene-related peptide
      (CGRP) and brain derived neurotropic factor (BDNF) were determined using novel
      western blotting based technology. Glutamate and substance P (SP) was determined
      using commercial available methods. Several new isoforms were found for NGF, CGRP
      and BDNF in saliva. The isoform pattern showed significant variation in both
      expression and chemiluminescence levels between different collection methods. New
      sensitive methods to study pain related markers in saliva were developed in this
      study. Furthermore, we are first to demonstrate a correlation between the
      Glutamate concentration in stimulated whole saliva and blood. However, the
      fundamental conclusion drawn is the importance of consistency in the collection
      method.

PMID- 29459714
TI  - The mycotoxin phomoxanthone A disturbs the form and function of the inner
      mitochondrial membrane.
AB  - Mitochondria are cellular organelles with crucial functions in the generation and
      distribution of ATP, the buffering of cytosolic Ca2+ and the initiation of
      apoptosis. Compounds that interfere with these functions are termed mitochondrial
      toxins, many of which are derived from microbes, such as antimycin A, oligomycin
      A, and ionomycin. Here, we identify the mycotoxin phomoxanthone A (PXA), derived
      from the endophytic fungus Phomopsis longicolla, as a mitochondrial toxin. We
      show that PXA elicits a strong release of Ca2+ from the mitochondria but not from
      the ER. In addition, PXA depolarises the mitochondria similarly to protonophoric
      uncouplers such as CCCP, yet unlike these, it does not increase but rather
      inhibits cellular respiration and electron transport chain activity. The
      respiration-dependent mitochondrial network structure rapidly collapses into
      fragments upon PXA treatment. Surprisingly, this fragmentation is independent
      from the canonical mitochondrial fission and fusion mediators DRP1 and OPA1, and
      exclusively affects the inner mitochondrial membrane, leading to cristae
      disruption, release of pro-apoptotic proteins, and apoptosis. Taken together, our
      results suggest that PXA is a mitochondrial toxin with a novel mode of action
      that might prove a useful tool for the study of mitochondrial ion homoeostasis
      and membrane dynamics.

PMID- 29459716
TI  - Common Deregulation of Seven Biological Processes by MicroRNAs in
      Gastrointestinal Cancers.
AB  - MicroRNAs are frequently dysregulated in human neoplasms, including
      gastrointestinal cancers. Nevertheless, the global influence of microRNA
      dysregulation on cellular signaling is still unknown. Here we sought to elucidate
      cellular signaling dysregulation by microRNAs in gastrointestinal cancers at the
      systems biology level followed by experimental validation. Signature dysregulated
      microRNAs in gastric, colorectal and liver cancers were defined based on our
      previous studies. Targets of signature dysregulated miRNAs were predicted using
      multiple computer algorithms followed by gene enrichment analysis to identify
      biological processes perturbed by dysregulated microRNAs. Effects of microRNAs on
      endocytosis were measured by epidermal growth factor (EGF) internalization assay.
      Our analysis revealed that, aside from well-established cancer-related signaling
      pathways, several novel pathways, including axon guidance, neurotrophin/nerve
      growth factor signaling, and endocytosis, were found to be involved in the
      pathogenesis of gastrointestinal cancers. The regulation of EGF receptor (EGFR)
      endocytosis by two predicted miRNAs, namely miR-17 and miR-145, was confirmed
      experimentally. Functionally, miR-145, which blocked EGFR endocytosis, prolonged
      EGFR membrane signaling and altered responsiveness of colon cancer cells to EGFR
      targeting drugs. In conclusion, our analysis depicts a comprehensive picture of
      cellular signaling dysregulation, including endocytosis, by microRNAs in
      gastrointestinal cancers.

PMID- 29459717
TI  - Silibinin alleviates inflammation and induces apoptosis in human rheumatoid
      arthritis fibroblast-like synoviocytes and has a therapeutic effect on arthritis
      in rats.
AB  - Silibinin, a natural polyphenolic flavonoid, possesses anti-oxidant, anti
      inflammation and anti-cancer properties. The present study was designed to
      investigate the effects of silibinin on rheumatoid arthritis (RA) pathogenesis
      related cells and collagen-induced arthritis (CIA) and further explore the
      potential underlying mechanisms. Our results showed that silibinin suppressed
      cell viability and increased the percentage of apoptotic RA-fibroblast-like
      synoviocytes (FLS). Furthermore, the production of inflammatory cytokines in RA
      FLS and a CIA rat model was effectively inhibited by silibinin. Silibinin also
      induced macrophage M2 polarization in RAW264.7 cells. We further demonstrated
      that silibinin inhibits Th17 cell differentiation in vitro. The nuclear factor
      kappa B (NF-kappaB) pathway was suppressed in RA-FLS. In addition, Sirtuin1
      (SIRT1) was decreased after silibinin treatment, and RA-FLS transfection with a
      short hairpin RNA (shRNA) of SIRT1 enhanced silibinin-induced apoptosis.
      Autophagy was markedly decreased in a dose-dependent manner following silibinin
      treatment. These findings indicate that silibinin inhibited inflammation by
      inhibiting the NF-kappaB pathway, and SIRT1 may participate in silibinin-induced
      apoptosis. Silibinin also inhibited autophagy in RA-FLS. Thus, silibinin may be a
      potential therapeutic agent for the treatment of RA.

PMID- 29459718
TI  - Systematic generation of biophysically detailed models for diverse cortical
      neuron types.
AB  - The cellular components of mammalian neocortical circuits are diverse, and
      capturing this diversity in computational models is challenging. Here we report
      an approach for generating biophysically detailed models of 170 individual
      neurons in the Allen Cell Types Database to link the systematic experimental
      characterization of cell types to the construction of cortical models. We build
      models from 3D morphologies and somatic electrophysiological responses measured
      in the same cells. Densities of active somatic conductances and additional
      parameters are optimized with a genetic algorithm to match electrophysiological
      features. We evaluate the models by applying additional stimuli and comparing
      model responses to experimental data. Applying this technique across a diverse
      set of neurons from adult mouse primary visual cortex, we verify that models
      preserve the distinctiveness of intrinsic properties between subsets of cells
      observed in experiments. The optimized models are accessible online alongside the
      experimental data. Code for optimization and simulation is also openly
      distributed.

PMID- 29459719
TI  - miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory
      T cell (tTreg).
AB  - Thymic-derived regulatory T cell (tTreg) clinical trials show therapeutic promise
      in the prevention of acute graft-versus-host disease (GVHD) in allogeneic
      hematopoietic stem cell transplantation patients. However, strategies are needed
      to improve tTreg proliferative ability and survival as a means to improve tTreg
      therapy and reduce the requirement for producing large numbers of Treg cells for
      adoptive tTreg transfer. Autophagy is a self-degradative process for cytosolic
      components, which is involved in cells death, differentiation, lymphocyte
      homeostasis, and tTreg function. Studies have shown that mice with tTreg cells
      that have a disrupted autophagy process have defective tTreg cell generation and
      function, resulting in autoimmune disease and failed GVHD prevention by
      adoptively transferred tTreg cells. We found the attenuated autophagy status
      during ex vivo expansion, which leads us to determine whether tTreg cell survival
      could be augmented by miR-142-3p, the miRNA which is highly expressed in tTreg
      cells and potentially targets autophagy-related protein (ATG)-1, ATG16L1. We
      demonstrate that miR-142-3p downregulates ATG16L1 mRNA and production of ATG16L1,
      that has been linked to autoimmune diseases. Conversely, miR-142-3p knock-down
      improved tTreg cell expansion, survival and function in vitro and vivo. In
      aggregate, these studies provide a new approach that uses miR-142-3p knockdown to
      increase tTreg cell efficacy by increasing ATG16L1 mRNA and protein and the
      autophagy process.

PMID- 29459720
TI  - Controlling striatal function via anterior frontal cortex stimulation.
AB  - Motivational, cognitive and action goals are processed by distinct,
      topographically organized, corticostriatal circuits. We aimed to test whether
      processing in the striatum is under causal control by cortical regions in the
      human brain by investigating the effects of offline transcranial magnetic
      stimulation (TMS) over distinct frontal regions associated with motivational,
      cognitive and action goal processing. Using a three-session counterbalanced
      within-subject crossover design, continuous theta burst stimulation was applied
      over the anterior prefrontal cortex (aPFC), dorsolateral prefrontal cortex, or
      premotor cortex, immediately after which participants (N = 27) performed a
      paradigm assessing reward anticipation (motivation), task (cognitive) switching,
      and response (action) switching. Using task-related functional magnetic resonance
      imaging (fMRI), we assessed the effects of stimulation on processing in distinct
      regions of the striatum. To account for non-specific effects, each session
      consisted of a baseline (no-TMS) and a stimulation (post-TMS) fMRI run.
      Stimulation of the aPFC tended to decrease reward-related processing in the
      caudate nucleus, while stimulation of the other sites was unsuccessful. A follow
      up analysis revealed that aPFC stimulation also decreased processing in the
      putamen as a function of the interaction between all factors (reward, cognition
      and action), suggesting stimulation modulated the transfer of motivational
      information to cortico-striatal circuitry associated with action control.

PMID- 29459721
TI  - Debye formulas for a relaxing system with memory.
AB  - Rate (master) equations are ubiquitous in statistical physics, yet, to the best
      of our knowledge, a rate equation with memory has previously never been
      considered. We write down an integro-differential rate equation for the evolution
      of a thermally relaxing system with memory. For concreteness we adopt as a model
      a single-domain magnetic particle driven by a small ac field and derive the
      modified Debye formulas. For any memory time Theta the in-phase component of the
      resultant ac susceptibility is positive at small probing frequencies omega, but
      becomes negative at large omega. The system thus exhibits frequency induced
      diamagnetism. For comparison we also consider particle pairs with dipolar
      coupling. The memory effect is found to be enhanced by ferromagnetic coupling and
      suppressed by antiferromagnetic coupling. Numerical calculations support the
      prediction of a negative susceptibility which arises from a phase shift induced
      by the memory effect. It is proposed that the onset of frequency induced
      diamagnetism represents a viable experimental signature of correlated noise.

PMID- 29459722
TI  - Vesicle-based secretion in schistosomes: Analysis of protein and microRNA (miRNA)
      content of exosome-like vesicles derived from Schistosoma mansoni.
AB  - Exosomes are small vesicles of endocytic origin, which are released into the
      extracellular environment and mediate a variety of physiological and pathological
      conditions. Here we show that Schistosoma mansoni releases exosome-like vesicles
      in vitro. Vesicles were purified from culture medium by sucrose gradient
      fractionation and fractions containing vesicles verified by western blot analyses
      and electron microscopy. Proteomic analyses of exosomal contents unveiled 130
      schistosome proteins. Among these proteins are common exosomal markers such as
      heat shock proteins, energy-generating enzymes, cytoskeletal proteins, and
      others. In addition, the schistosome extracellular vesicles contain proteins of
      potential importance for host-parasite interaction, notably peptidases, signaling
      proteins, cell adhesion proteins (e.g., integrins) and previously described
      vaccine candidates, including glutathione-S-transferase (GST), tetraspanin (TSP
      2) and calpain. S. mansoni exosomes also contain 143 microRNAs (miRNA), of which
      25 are present at high levels, including miRNAs detected in sera of infected
      hosts. Quantitative PCR analysis confirmed the presence of schistosome-derived
      miRNAs in exosomes purified from infected mouse sera. The results provide
      evidence of vesicle-mediated secretion in these parasites and suggest that
      schistosome-derived exosomes could play important roles in host-parasite
      interactions and could be a useful tool in the development of vaccines and
      therapeutics.

PMID- 29459723
TI  - Generalized leaky integrate-and-fire models classify multiple neuron types.
AB  - There is a high diversity of neuronal types in the mammalian neocortex. To
      facilitate construction of system models with multiple cell types, we generate a
      database of point models associated with the Allen Cell Types Database. We
      construct a set of generalized leaky integrate-and-fire (GLIF) models of
      increasing complexity to reproduce the spiking behaviors of 645 recorded neurons
      from 16 transgenic lines. The more complex models have an increased capacity to
      predict spiking behavior of hold-out stimuli. We use unsupervised methods to
      classify cell types, and find that high level GLIF model parameters are able to
      differentiate transgenic lines comparable to electrophysiological features. The
      more complex model parameters also have an increased ability to differentiate
      between transgenic lines. Thus, creating simple models is an effective
      dimensionality reduction technique that enables the differentiation of cell types
      from electrophysiological responses without the need for a priori-defined
      features. This database will provide a set of simplified models of multiple cell
      types for the community to use in network models.

PMID- 29459725
TI  - One effector at a time.

PMID- 29459724
TI  - Assessment of soil heavy metals for eco-environment and human health in a rapidly
      urbanization area of the upper Yangtze Basin.
AB  - Soil pollution with heavy metals (HMs) has been attracting more and more
      interests, however, assessment of eco-environmental and human risks particularly
      in a rapidly urbanization area (the upper Yangtze) remains limited. Multiple
      modern indices were firstly performed for complete risk assessment of eco
      environment and human health based on a high-spatial-resolution sampling.
      Averages of HMs were far below grade II threshold level of the Chinese
      Environmental Quality standards for soils, whereas Cd, As and Hg considerably
      exceeded the local background values. EF suggested overall moderate enrichments
      of Cd and Se, resulting in soils uncontaminated to moderately contaminated with
      them. Potential ecological risk index showed significant differences among
      Counties that were characterized by moderate risk. However, several sites were
      moderately to heavily contaminated with As, Cd and Hg by Igeo, resulting in that
      these sites were categorized as "considerable risk", or "high risk". Moreover,
      children were more susceptible to the potential health risk irrespective of the
      carcinogenic or non - carcinogenic risk. There were no significant carcinogenic
      and non - carcinogenic risks for adults, children however showed significant non 
      carcinogenic effect. Our first assessment provided important information for
      policy making to reduce the potential effects of soil contamination on human and
      eco-environment.

PMID- 29459726
TI  - The systemin receptor SYR1 enhances resistance of tomato against herbivorous
      insects.
AB  - The discovery in tomato of systemin, the first plant peptide hormone1,2, was a
      fundamental change for the concept of plant hormones. Numerous other peptides
      have since been shown to play regulatory roles in many aspects of the plant life,
      including growth, development, fertilization and interactions with symbiotic
      organisms3-6. Systemin, an 18 amino acid peptide derived from a larger precursor
      protein 7 , was proposed to act as the spreading signal that triggers systemic
      defence responses observed in plants after wounding or attack by herbivores1,7,8.
      Further work culminated in the identification of a leucine-rich repeat receptor
      kinase (LRR-RK) as the systemin receptor 160 (SR160)9,10. SR160 is a tomato
      homologue of Brassinosteroid Insensitive 1 (BRI1), which mediates the regulation
      of growth and development in response to the steroid hormone brassinolide11-13.
      However, a role of SR160/BRI1 as systemin receptor could not be corroborated by
      others14-16. Here, we demonstrate that perception of systemin depends on a pair
      of distinct LRR-RKs termed SYR1 and SYR2. SYR1 acts as a genuine systemin
      receptor that binds systemin with high affinity and specificity. Further, we show
      that presence of SYR1, although not decisive for local and systemic wound
      responses, is important for defence against insect herbivory.

PMID- 29459727
TI  - Farming with crops and rocks to address global climate, food and soil security.
AB  - The magnitude of future climate change could be moderated by immediately reducing
      the amount of CO2 entering the atmosphere as a result of energy generation and by
      adopting strategies that actively remove CO2 from it. Biogeochemical improvement
      of soils by adding crushed, fast-reacting silicate rocks to croplands is one such
      CO2-removal strategy. This approach has the potential to improve crop production,
      increase protection from pests and diseases, and restore soil fertility and
      structure. Managed croplands worldwide are already equipped for frequent rock
      dust additions to soils, making rapid adoption at scale feasible, and the
      potential benefits could generate financial incentives for widespread adoption in
      the agricultural sector. However, there are still obstacles to be surmounted.
      Audited field-scale assessments of the efficacy of CO2 capture are urgently
      required together with detailed environmental monitoring. A cost-effective way to
      meet the rock requirements for CO2 removal must be found, possibly involving the
      recycling of silicate waste materials. Finally, issues of public perception,
      trust and acceptance must also be addressed.

PMID- 29459728
TI  - Silencing SlMED18, tomato Mediator subunit 18 gene, restricts internode
      elongation and leaf expansion.
AB  - Mediator complex, a conserved multi-protein, is necessary for controlling RNA
      polymerase II (Pol II) transcription in eukaryotes. Given little is known about
      them in tomato, a tomato Mediator subunit 18 gene was isolated and named SlMED18.
      To further explore the function of SlMED18, the transgenic tomato plants
      targeting SlMED18 by RNAi-mediated gene silencing were generated. The SlMED18
      RNAi lines exhibited multiple developmental defects, including smaller size and
      slower growth rate of plant and significantly smaller compound leaves. The
      contents of endogenous bioactive GA3 in SlMED18 silenced lines were slightly less
      than that in wild type. Furthermore, qRT-PCR analysis indicated that expression
      of gibberellins biosynthesis genes such as SlGACPS and SlGA20x2, auxin transport
      genes (PIN1, PIN4, LAX1 and LAX2) and several key regulators, KNOX1, KNOX2, PHAN
      and LANCEOLATE(LA), which involved in the leaf morphogenesis were significantly
      down-regulated in SlMED18-RNAi lines. These results illustrated that SlMED18
      plays an essential role in regulating plant internode elongation and leaf
      expansion in tomato plants and it acts as a key positive regulator of
      gibberellins biosynthesis and signal transduction as well as auxin proper
      transport signalling. These findings are the basis for understanding the function
      of the individual Mediator subunits in tomato.

PMID- 29459729
TI  - New Zealand glowworm (Arachnocampa luminosa) bioluminescence is produced by a
      firefly-like luciferase but an entirely new luciferin.
AB  - The New Zealand glowworm, Arachnocampa luminosa, is well-known for displays of
      blue-green bioluminescence, but details of its bioluminescent chemistry have been
      elusive. The glowworm is evolutionarily distant from other bioluminescent
      creatures studied in detail, including the firefly. We have isolated and
      characterised the molecular components of the glowworm luciferase-luciferin
      system using chromatography, mass spectrometry and 1H NMR spectroscopy. The
      purified luciferase enzyme is in the same protein family as firefly luciferase
      (31% sequence identity). However, the luciferin substrate of this enzyme is
      produced from xanthurenic acid and tyrosine, and is entirely different to that of
      the firefly and known luciferins of other glowing creatures. A candidate
      luciferin structure is proposed, which needs to be confirmed by chemical
      synthesis and bioluminescence assays. These findings show that luciferases can
      evolve independently from the same family of enzymes to produce light using
      structurally different luciferins.

PMID- 29459730
TI  - A single NaK channel conformation is not enough for non-selective ion conduction.
AB  - NaK and other non-selective channels are able to conduct both sodium (Na+) and
      potassium (K+) with equally high efficiency. In contrast to previous
      crystallographic results, we show that the selectivity filter (SF) of NaK in
      native-like lipid membranes adopts two distinct conformations that are stabilized
      by either Na+ or K+ ions. The atomic differences of these conformations are
      resolved by solid-state NMR (ssNMR) spectroscopy and molecular dynamics (MD)
      simulations. Besides the canonical K+ permeation pathway, we identify a side
      entry ion-conduction pathway for Na+ permeation unique to NaK. Moreover, under
      otherwise identical conditions ssNMR spectra of the K+ selective NaK mutant
      (NaK2K) reveal only a single conformational state. Therefore, we propose that
      structural plasticity within the SF and the selection of these conformations by
      different ions are key molecular determinants for highly efficient conduction of
      different ions in non-selective cation channels.

PMID- 29459731
TI  - Involvement of impaired autophagy and mitophagy in Neuro-2a cell damage under
      hypoxic and/or high-glucose conditions.
AB  - Chronic cerebral hypoperfusion (CCH) plays an insidious role in the development
      of cognitive impairment. Considerable evidence suggests that Diabetes Mellitus
      (DM) as a vascular risk factor may exacerbate CCH and is closely related to
      cognitive decline. Dysregulation of autophagy is known to be associated with the
      pathogenesis of neurodegenerative diseases such as Alzheimer's disease. To
      elucidate the role of autophagy in CCH- and/or DM-related pathogenesis, mouse
      neuroblastoma Neuro-2a cells were exposed to hypoxia and/or high glucose for 48
      h, mimicking CCH complicated with DM pathologies. Chronic hypoxia reduced cell
      proliferation and increased levels of cleaved caspase-3, whereas high glucose had
      no obvious synergistic toxic effect. Accumulation of autophagic vacuoles under
      hypoxia may be due to both autophagy impairment and induction, with the former
      accounting for Neuro-2a cell death. Additionally, aberrant accumulation of
      mitochondria in Neuro-2a cells may be attributed to insufficient BNIP3-mediated
      mitophagy due to poor interaction between BNIP3 and LC3-II. Despite the lack of a
      significant cytotoxic effect of high glucose under our experimental conditions,
      our data indicated for the first time that impaired autophagy degradation and
      inefficient BNIP3-mediated mitophagy may constitute mechanisms underlying
      neuronal cell damage during chronic hypoxia.

PMID- 29459732
TI  - A protease cascade regulates release of the human malaria parasite Plasmodium
      falciparum from host red blood cells.
AB  - Malaria parasites replicate within a parasitophorous vacuole in red blood cells
      (RBCs). Progeny merozoites egress upon rupture of first the parasitophorous
      vacuole membrane (PVM), then poration and rupture of the RBC membrane (RBCM).
      Egress is protease-dependent 1 , but none of the effector molecules that mediate
      membrane rupture have been identified and it is unknown how sequential rupture of
      the two membranes is controlled. Minutes before egress, the parasite serine
      protease SUB1 is discharged into the parasitophorous vacuole2-6 where it cleaves
      multiple substrates2,5,7-9 including SERA6, a putative cysteine protease10-12.
      Here, we show that Plasmodium falciparum parasites lacking SUB1 undergo none of
      the morphological transformations that precede egress and fail to rupture the
      PVM. In contrast, PVM rupture and RBCM poration occur normally in SERA6-null
      parasites but RBCM rupture does not occur. Complementation studies show that
      SERA6 is an enzyme that requires processing by SUB1 to function. RBCM rupture is
      associated with SERA6-dependent proteolytic cleavage within the actin-binding
      domain of the major RBC cytoskeletal protein beta-spectrin. We conclude that SUB1
      and SERA6 play distinct, essential roles in a coordinated proteolytic cascade
      that enables sequential rupture of the two bounding membranes and culminates in
      RBCM disruption through rapid, precise, SERA6-mediated disassembly of the RBC
      cytoskeleton.

PMID- 29459733
TI  - Conditional toxicity and synergy drive diversity among antibacterial effectors.
AB  - Bacteria in polymicrobial habitats contend with a persistent barrage of
      competitors, often under rapidly changing environmental conditions 1 . The direct
      antagonism of competitor cells is thus an important bacterial survival strategy 2
      . Towards this end, many bacterial species employ an arsenal of antimicrobial
      effectors with multiple activities; however, the benefits conferred by the
      simultaneous deployment of diverse toxins are unknown. Here we show that the
      multiple effectors delivered to competitor bacteria by the type VI secretion
      system (T6SS) of Pseudomonas aeruginosa display conditional efficacy and act
      synergistically. One of these effectors, Tse4, is most active in high-salinity
      environments and synergizes with effectors that degrade the cell wall or
      inactivate intracellular electron carriers. We find Tse4 synergizes with these
      disparate mechanisms by forming pores that disrupt the DeltaPsi component of the
      proton motive force. Our results provide evidence that the concomitant delivery
      of a cocktail of effectors serves as a bet-hedging strategy to promote bacterial
      competitiveness in the face of unpredictable and variable environmental
      conditions.

PMID- 29459734
TI  - The CaV2alpha1 EF-hand F helix tyrosine, a highly conserved locus for GPCR
      inhibition of CaV2 channels.
AB  - The sensory neuron of Aplysia californica participates in several forms of
      presynaptic plasticity including homosynaptic depression, heterosynaptic
      depression, facilitation and the reversal of depression. The calcium channel
      triggering neurotransmitter release at most synapses is CaV2, consisting of the
      pore forming alpha1 subunit (CaV2alpha1), and auxiliary CaVbeta, and
      CaValpha2delta subunits. To determine the role of the CaV2 channel in presynaptic
      plasticity in Aplysia, we cloned Aplysia CaV2alpha1, CaVbeta, and CaValpha2delta
      and over-expressed the proteins in Aplysia sensory neurons (SN). We show
      expression of exogenous CaV2alpha1 in the neurites of cultured Aplysia SN. One
      proposed mechanism for heterosynaptic depression in Aplysia is through inhibition
      of CaV2. Here, we demonstrate that heterosynaptic depression of the CaV2 calcium
      current is inhibited when a channel with a Y-F mutation at the conserved Src
      phosphorylation site is expressed, showing the strong conservation of this
      mechanism over evolution. We also show that the Y-F mutation reduces
      heterosynaptic inhibition of neurotransmitter release, highlighting the
      physiological importance of this mechanism for the regulation of synaptic
      efficacy. These results also demonstrate our ability to replace endogenous CaV2
      channels with recombinant channels allowing future examination of the structure
      function relationship of CaV2 in the regulation of transmitter release in this
      system.

PMID- 29459735
TI  - Structural heterogeneity of the rat pulmonary vein myocardium: consequences on
      intracellular calcium dynamics and arrhythmogenic potential.
AB  - Mechanisms underlying ectopic activity in the pulmonary vein (PV) which triggers
      paroxysmal atrial fibrillation are unknown. Although several studies have
      suggested that calcium signalling might be involved in these arrhythmias, little
      is known about calcium cycling in PV cardiomyocytes (CM). We found that
      individual PV CM showed a wide range of transverse tubular incidence and
      organization, going from their virtual absence, as described in atrial CM, to
      well transversally organised tubular systems, like in ventricular CM. These
      different types of CM were found in groups scattered throughout the tissue. The
      variability of the tubular system was associated with cell to cell heterogeneity
      of calcium channel (Cav1.2) localisation and, thereby, of Cav1.2-Ryanodine
      receptor coupling. This was responsible for multiple forms of PV CM calcium
      transient. Spontaneous calcium sparks and waves were not only more abundant in PV
      CM than in LA CM but also associated with a higher depolarising current. In
      conclusion, compared with either the atrium or the ventricle, PV myocardium
      presents marked structural and functional heterogeneity.

PMID- 29459736
TI  - Photonic-crystal exciton-polaritons in monolayer semiconductors.
AB  - Semiconductor microcavity polaritons, formed via strong exciton-photon coupling,
      provide a quantum many-body system on a chip, featuring rich physics phenomena
      for better photonic technology. However, conventional polariton cavities are
      bulky, difficult to integrate, and inflexible for mode control, especially for
      room-temperature materials. Here we demonstrate sub-wavelength-thick, one
      dimensional photonic crystals as a designable, compact, and practical platform
      for strong coupling with atomically thin van der Waals crystals. Polariton
      dispersions and mode anti-crossings are measured up to room temperature. Non
      radiative decay to dark excitons is suppressed due to polariton enhancement of
      the radiative decay. Unusual features, including highly anisotropic dispersions
      and adjustable Fano resonances in reflectance, may facilitate high temperature
      polariton condensation in variable dimensions. Combining slab photonic crystals
      and van der Waals crystals in the strong coupling regime allows unprecedented
      engineering flexibility for exploring novel polariton phenomena and device
      concepts.

PMID- 29459737
TI  - Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in
      optic nerve head astrocytes.
AB  - Glaucoma is characterized by a progressive loss of retinal ganglion cells and
      their axons, but the underlying biological basis for the accompanying
      neurodegeneration is not known. Accumulating evidence indicates that structural
      and functional abnormalities of astrocytes within the optic nerve head (ONH) have
      a role. However, whether the activation of cyclic adenosine 3',5'-monophosphate
      (cAMP) signaling pathway is associated with astrocyte dysfunction in the ONH
      remains unknown. We report here that the cAMP/protein kinase A (PKA) pathway is
      critical to ONH astrocyte dysfunction, leading to caspase-3 activation and cell
      death via the AKT/Bim/Bax signaling pathway. Furthermore, elevated intracellular
      cAMP exacerbates vulnerability to oxidative stress in ONH astrocytes, and this
      may contribute to axonal damage in glaucomatous neurodegeneration. Inhibition of
      intracellular cAMP/PKA signaling activation protects ONH astrocytes by increasing
      AKT phosphorylation against oxidative stress. These results strongly indicate
      that activation of cAMP/PKA pathway has an important role in astrocyte
      dysfunction, and suggest that modulating cAMP/PKA pathway has therapeutic
      potential for glaucomatous ONH degeneration.

PMID- 29459738
TI  - Epistasis between FLG and IL4R Genes on the Risk of Allergic Sensitization:
      Results from Two Population-Based Birth Cohort Studies.
AB  - Immune-specific genes as well as genes responsible for the formation and
      integrity of the epidermal barrier have been implicated in the pathogeneses of
      allergic sensitization. This study sought to determine whether an epistatic
      effect (gene-gene interaction) between genetic variants within interleukin 4
      receptor (IL4R) and filaggrin (FLG) genes predispose to the development of
      allergic sensitization. Data from two birth cohort studies were analyzed, namely
      the Isle of Wight (IOW; n = 1,456) and the Manchester Asthma and Allergy Study
      (MAAS; n = 1,058). In the IOW study, one interaction term (IL4R rs3024676 * FLG
      variants) showed statistical significance (interaction term: P = 0.003). To
      illustrate the observed epistasis, stratified analyses were performed, which
      showed that FLG variants were associated with allergic sensitization only among
      IL4R rs3024676 homozygotes (OR, 1.97; 95% CI, 1.27-3.05; P = 0.003). In contrast,
      FLG variants effect was masked among IL4R rs3024676 heterozygotes (OR, 0.53; 95%
      CI, 0.22-1.32; P = 0.175). Similar results were demonstrated in the MAAS study.
      Epistasis between immune (IL4R) and skin (FLG) regulatory genes exist in the
      pathogenesis of allergic sensitization. Hence, genetic susceptibility towards
      defective epidermal barrier and deviated immune responses could work together in
      the development of allergic sensitization.

PMID- 29459740
TI  - Author Correction: Additive manufacture of complex 3D Au-containing
      nanocomposites by simultaneous two-photon polymerisation and photoreduction.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 29459739
TI  - Localization of adaptive variants in human genomes using averaged one-dependence
      estimation.
AB  - Statistical methods for identifying adaptive mutations from population genetic
      data face several obstacles: assessing the significance of genomic outliers,
      integrating correlated measures of selection into one analytic framework, and
      distinguishing adaptive variants from hitchhiking neutral variants. Here, we
      introduce SWIF(r), a probabilistic method that detects selective sweeps by
      learning the distributions of multiple selection statistics under different
      evolutionary scenarios and calculating the posterior probability of a sweep at
      each genomic site. SWIF(r) is trained using simulations from a user-specified
      demographic model and explicitly models the joint distributions of selection
      statistics, thereby increasing its power to both identify regions undergoing
      sweeps and localize adaptive mutations. Using array and exome data from 45
      ?Khomani San hunter-gatherers of southern Africa, we identify an enrichment of
      adaptive signals in genes associated with metabolism and obesity. SWIF(r)
      provides a transparent probabilistic framework for localizing beneficial
      mutations that is extensible to a variety of evolutionary scenarios.

PMID- 29459741
TI  - A fuzzy feature fusion method for auto-segmentation of gliomas with multi
      modality diffusion and perfusion magnetic resonance images in radiotherapy.
AB  - The diffusion and perfusion magnetic resonance (MR) images can provide functional
      information about tumour and enable more sensitive detection of the tumour
      extent. We aimed to develop a fuzzy feature fusion method for auto-segmentation
      of gliomas in radiotherapy planning using multi-parametric functional MR images
      including apparent diffusion coefficient (ADC), fractional anisotropy (FA) and
      relative cerebral blood volume (rCBV). For each functional modality, one
      histogram-based fuzzy model was created to transform image volume into a fuzzy
      feature space. Based on the fuzzy fusion result of the three fuzzy feature
      spaces, regions with high possibility belonging to tumour were generated
      automatically. The auto-segmentations of tumour in structural MR images were
      added in final auto-segmented gross tumour volume (GTV). For evaluation, one
      radiation oncologist delineated GTVs for nine patients with all modalities.
      Comparisons between manually delineated and auto-segmented GTVs showed that, the
      mean volume difference was 8.69% (+/-5.62%); the mean Dice's similarity
      coefficient (DSC) was 0.88 (+/-0.02); the mean sensitivity and specificity of
      auto-segmentation was 0.87 (+/-0.04) and 0.98 (+/-0.01) respectively. High
      accuracy and efficiency can be achieved with the new method, which shows
      potential of utilizing functional multi-parametric MR images for target
      definition in precision radiation treatment planning for patients with gliomas.

PMID- 29459742
TI  - Impact of aromatase absence on murine intraocular pressure and retinal ganglion
      cells.
AB  - We hypothesize that aromatase, an enzyme that regulates estrogen production,
      plays a significant role in the control of intraocular pressure (IOP) and retinal
      ganglion cells (RGCs). To begin to test our hypothesis, we examined the impact of
      aromatase absence, which completely eliminates estrogen synthesis, in male and
      female mice. Studies were performed with adult, age-matched wild type (WT) and
      aromatase knockout (ArKO) mice. IOP was measured in a masked fashion in both eyes
      of conscious mice at 12 and 24 weeks of age. Retinas were obtained and processed
      for RGC counting with a confocal microscope. IOP levels in both 12- and 24-week
      old female ArKO mice were significantly higher than those of age- and sex-matched
      WT controls. The mean increase in IOP was 7.9% in the 12-week-, and 19.7% in the
      24-week-old mice, respectively. These changes were accompanied by significant 9%
      and 7% decreases in RGC numbers in the ArKO female mice, relative to controls, at
      12- and 24-weeks, respectively. In contrast, aromatase deficiency did not lead to
      an increased IOP in male mice. There was a significant reduction in RGC counts in
      the 12-, but not 24-, week-old male ArKO mice, as compared to their age- and sex
      matched WT controls. Overall, our findings show that aromatase inhibition in
      females is associated with elevated IOP and reduced RGC counts.

PMID- 29459743
TI  - Gray and white matter integrity influence TMS signal propagation: a multimodal
      evaluation in cocaine-dependent individuals.
AB  - Transcranial magnetic stimulation (TMS) can stimulate cortical and subcortical
      brain regions. However, in order to reach subcortical targets, intact
      monosynaptic connections are required. The goal of this investigation was to
      evaluate the contribution of white matter integrity and gray matter volume to
      frontal pole TMS-evoked striatal activity in a large cohort of chronic cocaine
      users. 49 cocaine users received single pulses of TMS to the frontal pole while
      BOLD data were acquired - a technique known as interleaved TMS/fMRI. Diffusion
      tensor imaging and voxel-based morphometry were used to quantify white matter
      integrity and gray matter volume (GMV), respectively. Stepwise regression was
      used to evaluate the contribution of clinical and demographic variables to TMS
      evoked BOLD. Consistent with previous studies, frontal pole TMS evoked activity
      in striatum and salience circuitry. The size of the TMS-evoked response was
      related to fractional anisotropy between the frontal pole and putamen and GMV in
      the left frontal pole and left ACC. This is the first study to demonstrate that
      the effect of TMS on subcortical activity is dependent upon the structural
      integrity of the brain. These data suggest that these structural neuroimaging
      data types are biomarkers for TMS-induced mobilization of the striatum.

PMID- 29459744
TI  - Calpain7 impairs embryo implantation by downregulating beta3-integrin expression
      via degradation of HOXA10.
AB  - Endometriosis (ENDO) is a common gynecological disease that causes infertility in
      many women. Previous studies noted that the dysregulation of Homeo box A10
      (HOXA10) in the endometrium of women with ENDO was involved in the failure of
      embryo implantation. However, the mechanism by which HOXA10 expression is reduced
      in women with ENDO is still poorly understood. Here we found that a member of the
      calcium (Ca2+)-dependent cysteine protease family calpain7 (CAPN7), negatively
      correlated with HOXA10, was highly expressed in the endometrium of infertile
      women with ENDO and was significantly downregulated during the window of embryo
      implantation in mice. Overexpression of CAPN7 in Ishikawa cells or in the uterus
      of mice inhibited embryo implantation in vitro and in vivo. In the current study,
      we identified a sequence rich in proline, glutamic acid, serine, and threonine
      (PEST sequence) that enhanced the Ca2+-dependent degradation of HOXA10 by CAPN7.
      Furthermore, the interaction between HOXA10 and CAPN7 repressed the
      transcriptional activity and protein stability of HOXA10. In contrast, the
      administration of the calpain inhibitor ALLN reversed the CAPN7-induced HOXA10
      degradation. Moreover, truncation of the PEST motif in HOXA10 abolished its CAPN7
      dependent proteolysis. These studies reveal a novel pattern of HOXA10 regulation
      via PEST sequence-mediated calpain proteolysis that was demonstrated to be
      reversed by a calpain inhibitor. Thus, the inhibition of CAPN7-induced HOXA10
      degradation may represent a novel potential therapeutic method to improve
      impaired embryo implantation in women with ENDO.

PMID- 29459745
TI  - Joint Effect of Non-invasive Central Systolic Blood Pressure and Peripheral
      Systolic Blood Pressure on Incident Hypertension in a Chinese Community-based
      Population.
AB  - Central blood pressure level is not always consistent with peripheral blood
      pressure level, and especially their joint effect on incident hypertension is not
      well established. A total of 1607 non-hypertensive subjects from an
      atherosclerosis cohort in Beijing, China were included. Central systolic blood
      pressure (cSBP) was obtained using Omron HEM-9000AI machine and peripheral
      systolic blood pressure (pSBP) was measured using Omron HEM-7117 electronic
      sphygmomanometer, separately. Hypertension was defined as BP >= 140/90 mmHg or
      self-reported hypertension or taking any antihypertension drugs at the follow-up
      survey. After a median follow-up of 2.3 years, incident hypertension was 13.1%.
      Every 1 standard deviation increase of cSBP and pSBP was associated with 1.98
      (95%CI: 1.69-2.33) and 2.84 (95%CI: 2.30-3.52) times of incident hypertension
      after adjustment for confounders. Moreover, hypertension risk in single pSBP >=
      120 mmHg group, single cSBP >= 120 mmHg group, and both pSBP and cSBP >= 120 mmHg
      group was 2.83 (95%CI: 0.98-8.16), 3.28 (95%CI: 1.24-8.70), and 11.47 (95%CI:
      4.97-26.46) times higher than both pSBP and cSBP < 120 mmHg group, respectively.
      The joint effect of cSBP and pSBP is superior to either cSBP or pSBP to predict
      incident hypertension in a Chinese community-based population. Screening of
      central blood pressure should be considered in non-hypertensive population for
      the purpose of primary intervention, especially for subjects with pSBP >= 120
      mmHg.

PMID- 29459746
TI  - Simultaneous Strength-Ductility Enhancement of a Nano-Lamellar AlCoCrFeNi2.1
      Eutectic High Entropy Alloy by Cryo-Rolling and Annealing.
AB  - Nano-lamellar (L12 + B2) AlCoCrFeNi2.1 eutectic high entropy alloy (EHEA) was
      processed by cryo-rolling and annealing. The EHEA developed a novel hierarchical
      microstructure featured by fine lamellar regions consisting of FCC lamellae
      filled with ultrafine FCC grains (average size ~200-250 nm) and B2 lamellae, and
      coarse non-lamellar regions consisting of ultrafine FCC (average size ~200-250
      nm), few coarse recrystallized FCC grains and rather coarse unrecrystallized B2
      phase (~2.5 um). This complex and hierarchical microstructure originated from
      differences in strain-partitioning amongst the constituent phases, affecting the
      driving force for recrystallization. The hierarchical microstructure of the cryo
      rolled and annealed material resulted in simultaneous enhancement in strength
      (Yield Strength/YS: 1437 +/- 26 MPa, Ultimate Tensile Strength/UTS: 1562 +/- 33
      MPa) and ductility (elongation to failure/ef ~ 14 +/- 1%) as compared to the as
      cast as well as cold-rolled and annealed materials. The present study for the
      first time demonstrated that cryo-deformation and annealing could be a novel
      microstructural design strategy for overcoming strength-ductility trade off in
      multiphase high entropy alloys.

PMID- 29459747
TI  - Universal strategy for Ohmic hole injection into organic semiconductors with high
      ionization energies.
AB  - Barrier-free (Ohmic) contacts are a key requirement for efficient organic
      optoelectronic devices, such as organic light-emitting diodes, solar cells, and
      field-effect transistors. Here, we propose a simple and robust way of forming an
      Ohmic hole contact on organic semiconductors with a high ionization energy (IE).
      The injected hole current from high-work-function metal-oxide electrodes is
      improved by more than an order of magnitude by using an interlayer for which the
      sole requirement is that it has a higher IE than the organic semiconductor.
      Insertion of the interlayer results in electrostatic decoupling of the electrode
      from the semiconductor and realignment of the Fermi level with the IE of the
      organic semiconductor. The Ohmic-contact formation is illustrated for a number of
      material combinations and solves the problem of hole injection into organic
      semiconductors with a high IE of up to 6 eV.

PMID- 29459748
TI  - Genesis, challenges and opportunities for colloidal lead halide perovskite
      nanocrystals.
AB  - Lead halide perovskites (LHPs) in the form of nanometre-sized colloidal crystals,
      or nanocrystals (NCs), have attracted the attention of diverse materials
      scientists due to their unique optical versatility, high photoluminescence
      quantum yields and facile synthesis. LHP NCs have a 'soft' and predominantly
      ionic lattice, and their optical and electronic properties are highly tolerant to
      structural defects and surface states. Therefore, they cannot be approached with
      the same experimental mindset and theoretical framework as conventional
      semiconductor NCs. In this Review, we discuss LHP NCs historical and current
      research pursuits, challenges in applications, and the related present and future
      mitigation strategies explored.

PMID- 29459749
TI  - Human Pressures on Natural Reserves in Yunnan Province and Management
      Implications.
AB  - The analysis of status and major sources of human pressures on natural reserves
      (NRs) is important for optimizing their management. This study selected
      population density, gross domestic product (GDP) density and areal percentage of
      human land use to reveal the human pressures of national and provincial NRs (NNRs
      and PNRs) in Yunnan Province, China. We calculated three types of internal and
      external human pressure index (HPI) and comprehensive HPI (CHPI) for NRs. Human
      pressures on most of NRs were slight and light, indicating that most of NRs were
      well protected. Human pressures on PNRs were higher than on NNRs; with respect to
      five types of NRs, geological relict NRs were facing the highest human pressures,
      followed by wetland ecosystem NRs. Land use and population density were the main
      human pressures on these NRs. Yunnan Province should put the highest emphasis on
      three NNRs and two Ramsar site PNRs with severe CHPI, secondly pay attention to
      eight conservation-oriented PNRs with extreme or severe CHPI. It's urgent for
      Yunnan to implement scientific policies and measures to reduce land use and
      population density pressures of NRs, especially with severe and extreme CHPI, by
      transforming internal land use and/or implementing residents' eco-migration.

PMID- 29459750
TI  - Climate variability in the northern and southern Altai Mountains during the past
      50 years.
AB  - The Holocene drying trend in the northern Altai Mountains and the wetting trend
      in the southern Altai Mountains inferred from the paleoclimatic studies indicated
      it is needed to understand the modern climatic characters in this region.
      However, a detailed analysis of modern climate variations in the northern and
      southern Altai Mountains is lacking. Here, we investigate the monthly temperature
      and monthly precipitation data from seventeen meteorological stations during 1966
      2015 in the northern and southern Altai. The result shows that temperature
      increases significantly in the northern (0.42  degrees C/10 yr) and in the
      southern (0.54  degrees C/10 yr). The precipitation decreases insignificantly (
      1.41 mm/10 yr) in the northern, whereas it increases significantly (8.89 mm/10
      yr) in the southern. The out-of-phase relationship of precipitation changes is
      also recorded at different time-scales (i.e., season, year, multi-decades,
      centennial and millennial scales), indicating the Altai Mountains are an
      important climatic boundary. Based on the analysis of modern atmosphere
      circulation, the decreased precipitation in the northern corresponds to the
      decreasing contribution of 'Northern meridional and Stationary anticyclone' and
      'Northern meridional and East zonal' circulation and the increased precipitation
      in the southern are associated with the increasing contribution of 'West zonal
      and Southern meridional' circulation.

PMID- 29459751
TI  - Relevance of electrical current distribution to the forced flow and grain
      refinement in solidified Al-Si hypoeutectic alloy.
AB  - Significant grain refinement in cast metals can be achieved through the
      application of electric currents during the solidification process. The present
      paper investigates the distribution of electric currents on the grain size of
      solidified Al-7wt.%Si alloy under the application of electric current with
      constant parameters flowing through two parallel electrodes into the melt within
      a cylindrical mould. The distribution of electric current was controlled by
      applying an electrical insulation material coating, boron nitride (NB), to the
      sidewall of the electrodes. Experimental results showed that the employment of
      these insulated electrodes can reduce grain size in comparison with the reference
      case of electrodes without BN coating. Flow measurements were performed in Ga
      20wt.%In-12wt.%Sn liquid metal. Higher intensity forced flow occurred when the
      sidewall of the electrodes was insulated. In order to understand the underlying
      mechanism behind the stronger forced flow, corresponding numerical simulations
      were performed to reveal the distributions of the electric current, magnetic
      field, Lorentz force, and the resultant forced flow. The results achieved
      indicate that the mechanism of grain refinement driven by electric current is
      dendrite fragmentation induced by forced flow. In addition, a novel approach to
      enhance the grain refinement without additional input of current energy was
      developed.

PMID- 29459753
TI  - Cooling aerosols and changes in albedo counteract warming from CO2 and black
      carbon from forest bioenergy in Norway.
AB  - Climate impacts of forest bioenergy result from a multitude of warming and
      cooling effects and vary by location and technology. While past bioenergy studies
      have analysed a limited number of climate-altering pollutants and activities, no
      studies have jointly addressed supply chain greenhouse gas emissions, biogenic
      CO2 fluxes, aerosols and albedo changes at high spatial and process detail. Here,
      we present a national-level climate impact analysis of stationary bioenergy
      systems in Norway based on wood-burning stoves and wood biomass-based district
      heating. We find that cooling aerosols and albedo offset 60-70% of total warming,
      leaving a net warming of 340 or 69 kg CO2e MWh-1 for stoves or district heating,
      respectively. Large variations are observed over locations for albedo, and over
      technology alternatives for aerosols. By demonstrating both notable magnitudes
      and complexities of different climate warming and cooling effects of forest
      bioenergy in Norway, our study emphasizes the need to consider multiple forcing
      agents in climate impact analysis of forest bioenergy.

PMID- 29459756
TI  - Humility.
AB  - This paper offers a nuanced discourse on the otherwise ignored topic of humility.
      It brings together scattered comments within psychoanalysis, secular lay
      literature, sociocultural studies, and religious thought on humility. The paper
      also describes pathological variants of humility (excessive, deficient, false,
      and compartmentalized) and delineates five areas of clinical practice where
      humility plays an important role: (i) humility in selecting patients to treat,
      (ii) humility in daily conduct with patients, (iii) humility in the attitude of
      listening to clinical material, (iv) humility in the manner of intervening, and
      (v) humility in deciding upon the longevity of our professional careers.

PMID- 29459754
TI  - Cocaine-induced locomotor sensitization associates with slow oscillatory firing
      of neurons in the ventral tegmental area.
AB  - The initiation of psychostimulant sensitization depends on the mesocorticolimbic
      dopamine (DA) system. Although many cellular adaptations has been reported to be
      associated with this addictive behavior, the overall influence of these
      adaptations on the network regulation of DA neurons has not been established.
      Here, we profile a network-driven slow oscillation (SO) in the firing activity of
      ventral tegmental area (VTA) putative DA and non-DA neurons and their correlation
      with locomotor sensitization induced by repeated administration of cocaine. One
      day after the last cocaine injection, the power of SO (Pso) significantly
      increased both in DA and non-DA neurons. Interestingly, the Pso in DA neurons was
      positively correlated, while Pso in non-DA neurons was negatively correlated with
      the level of locomotor sensitization. On the other hand, the firing rates of DA
      and non-DA neurons were both elevated, but none exhibited any correlation with
      the level of sensitization. Fourteen days after the last injection, the Pso of DA
      neurons dissipated but still positively correlated with the level of
      sensitization. In contrast, the Pso in non-DA neurons lost correlation with
      locomotor sensitization. These results suggest that cocaine-induced locomotor
      sensitization is associated with long-term network adaptation in DA system and
      that DA and non-DA neurons may corporately facilitate/hamper the initiation of
      locomotor sensitization.

PMID- 29459752
TI  - Characterization of viral RNA splicing using whole-transcriptome datasets from
      host species.
AB  - RNA alternative splicing (AS) is an important post-transcriptional mechanism
      enabling single genes to produce multiple proteins. It has been well demonstrated
      that viruses deploy host AS machinery for viral protein productions. However,
      knowledge on viral AS is limited to a few disease-causing viruses in model
      species. Here we report a novel approach to characterizing viral AS using whole
      transcriptome dataset from host species. Two insect transcriptomes (Acheta
      domesticus and Planococcus citri) generated in the 1,000 Insect Transcriptome
      Evolution (1KITE) project were used as a proof of concept using the new pipeline.
      Two closely related densoviruses (Acheta domesticus densovirus, AdDNV, and
      Planococcus citri densovirus, PcDNV, Ambidensovirus, Densovirinae, Parvoviridae)
      were detected and analyzed for AS patterns. The results suggested that although
      the two viruses shared major AS features, dramatic AS divergences were observed.
      Detailed analysis of the splicing junctions showed clusters of AS events occurred
      in two regions of the virus genome, demonstrating that transcriptome analysis
      could gain valuable insights into viral splicing. When applied to large-scale
      transcriptomics projects with diverse taxonomic sampling, our new method is
      expected to rapidly expand our knowledge on RNA splicing mechanisms for a wide
      range of viruses.

PMID- 29459758
TI  - Ultrafast evolution of electric fields from high-intensity laser-matter
      interactions.
AB  - The interaction of high-power ultra-short lasers with materials offers
      fascinating wealth of transient phenomena which are in the core of novel
      scientific research. Deciphering its evolution is a complicated task that
      strongly depends on the details of the early phase of the interaction, which acts
      as complex initial conditions. The entire process, moreover, is difficult to
      probe since it develops close to target on the sub-picosecond timescale and ends
      after some picoseconds. Here we present experimental results related to the
      fields and charges generated by the interaction of an ultra-short high-intensity
      laser with metallic targets. The temporal evolution of the interaction is probed
      with a novel femtosecond resolution diagnostics that enables the differentiation
      of the contribution by the high-energy forerunner electrons and the radiated
      electromagnetic pulses generated by the currents of the remaining charges on the
      target surface. Our results provide a snapshot of huge pulses, up to 0.6 teravolt
      per meter, emitted with multi-megaelectronvolt electron bunches with sub
      picosecond duration and are able to explore the processes involved in laser
      matter interactions at the femtosecond timescale.

PMID- 29459759
TI  - Genomics of a pediatric ovarian fibrosarcoma. Association with the DICER1
      syndrome.
AB  - Ovarian fibrosarcomas are extremely rare tumors with little genomic information
      available to date. In the present report we present the tumoral exome and
      transcriptome and the germinal exome of an ovarian fibrosarcoma from a 9-years
      old child. We found a paucity of mutations (0.77/Mb) and CNV alterations. Of
      these, the most relevant were a point mutation in the metal-binding site of the
      microRNA-processing DICER1 enzyme and a frame-shift alteration in the tumor
      suppressor gene NF1. We validated a germinal truncating mutation in DICER1, which
      was consistent with a DICER1 Syndrome diagnosis, providing the first example of
      an ovarian fibrosarcoma as the presenting neoplasia in this syndrome. Network and
      enrichment analyses showed that both a mesenchymal signature and a Hedgehog
      cascade could be driving the progression of this tumor. We were also able to find
      a global lincRNA deregulation, as the number of lincRNAs transcripts expressed in
      the tumor was decreased, with a concomitant upregulation of previously described
      non-coding transcripts associated with cancer, such as MALAT1, MIR181A1HG, CASC1,
      XIST and FENDRR. DICER1 Syndrome should be considered as a possible diagnosis in
      children ovarian fibrosarcoma. The role of lncRNAs in neoplasias associated with
      DICER1 alterations need to be studied in more detail.

PMID- 29459760
TI  - Light pollution is greatest within migration passage areas for nocturnally
      migrating birds around the world.
AB  - Excessive or misdirected artificial light at night (ALAN) produces light
      pollution that influences several aspects of the biology and ecology of birds,
      including disruption of circadian rhythms and disorientation during flight. Many
      migrating birds traverse large expanses of land twice every year at night when
      ALAN illuminates the sky. Considering the extensive and increasing encroachment
      of light pollution around the world, we evaluated the association of the annual
      mean ALAN intensity over land within the geographic ranges of 298 nocturnally
      migrating bird species with five factors: phase of annual cycle, mean distance
      between breeding and non-breeding ranges, range size, global hemisphere of range,
      and IUCN category of conservation concern. Light pollution within geographic
      ranges was relatively greater during the migration season, for shorter-distance
      migrants, for species with smaller ranges, and for species in the western
      hemisphere. Our results suggest that migratory birds may be subject to the
      effects of light pollution particularly during migration, the most critical stage
      in their annual cycle. We hope these results will spur further research on how
      light pollution affects not only migrating birds, but also other highly mobile
      animals throughout their annual cycle.

PMID- 29459761
TI  - Matched case-control study of the influence of inland waters surrounding poultry
      farms on avian influenza outbreaks in Japan.
AB  - To successfully control highly pathogenic avian influenza (HPAI), understanding
      the risk factors related to the incursion of the virus into poultry farms is
      essential. In this study, we focused on the presence of inland waters surrounding
      poultry farms as a potential risk factor of incursion of the virus. To evaluate
      the influence of inland waters surrounding poultry farms on HPAI outbreaks in
      Japan, a simple matched case-control study was conducted. The results of the
      conditional regression analyses indicated that the number of farms with
      neighbouring inland waters was significantly high among the affected farms during
      the 2016-2017 outbreak period. These results provide good grounds for
      strengthening biosecurity management at farms located near inland waters.

PMID- 29459762
TI  - The characteristics of positive and confusing hand X-ray signs in diagnosing
      Kashin-Beck Disease in children in China.
AB  - When screening for Kashin-Beck disease (KBD) in children, hand X-ray examination
      is the most important measure. However, there is high rate of misdiagnosis
      because of confusing X-ray signs. We studied the characteristics of positive and
      confusing hand X-ray signs. Clinical and radiological examinations were conducted
      in all 7- to 12-year-olds in selected villages from some KBD and non-KBD areas.
      We analysed the radiological and epidemiological characteristics of the X-ray
      signs of KBD and the confusing signs. Images from 3,193 children were valid. No
      cases of KBD were found. Seventeen children (0.53%) had X-ray signs positive for
      KBD. The confusing X-ray signs included closure reaction of metaphysis-epiphysis
      (CRME, 14.28%), thumb variation (0.22%), little finger variation (8.89%), the
      second metacarpal-phalangeal variation (0.13%) and cystic change (3.85%). The
      onset of CRME in children occurred earlier in girls (9) than in boys (10). The
      onset occurred earlier in KBD areas (9) than in non-KBD areas (10). The onset
      occurred earlier in Han children (9) than in Tibetan children (11). In summary,
      KBD was effectively controlled in all investigated KBD endemic villages, and the
      age range should be adjusted to 7- to 11-year-olds in Han children to reduce the
      misdiagnosis rates in KBD surveillance.

PMID- 29459763
TI  - Single excitatory axons form clustered synapses onto CA1 pyramidal cell
      dendrites.
AB  - CA1 pyramidal neurons are a major output of the hippocampus and encode features
      of experience that constitute episodic memories. Feature-selective firing of
      these neurons results from the dendritic integration of inputs from multiple
      brain regions. While it is known that synchronous activation of spatially
      clustered inputs can contribute to firing through the generation of dendritic
      spikes, there is no established mechanism for spatiotemporal synaptic clustering.
      Here we show that single presynaptic axons form multiple, spatially clustered
      inputs onto the distal, but not proximal, dendrites of CA1 pyramidal neurons.
      These compound connections exhibit ultrastructural features indicative of strong
      synapses and occur much more commonly in entorhinal than in thalamic afferents.
      Computational simulations revealed that compound connections depolarize dendrites
      in a biophysically efficient manner, owing to their inherent spatiotemporal
      clustering. Our results suggest that distinct afferent projections use different
      connectivity motifs that differentially contribute to dendritic integration.

PMID- 29459764
TI  - Shared neural coding for social hierarchy and reward value in primate amygdala.
AB  - The social brain hypothesis posits that dedicated neural systems process social
      information. In support of this, neurophysiological data have shown that some
      brain regions are specialized for representing faces. It remains unknown,
      however, whether distinct anatomical substrates also represent more complex
      social variables, such as the hierarchical rank of individuals within a social
      group. Here we show that the primate amygdala encodes the hierarchical rank of
      individuals in the same neuronal ensembles that encode the rewards associated
      with nonsocial stimuli. By contrast, orbitofrontal and anterior cingulate
      cortices lack strong representations of hierarchical rank while still
      representing reward values. These results challenge the conventional view that
      dedicated neural systems process social information. Instead, information about
      hierarchical rank-which contributes to the assessment of the social value of
      individuals within a group-is linked in the amygdala to representations of
      rewards associated with nonsocial stimuli.

PMID- 29459765
TI  - Filling the Gaps in the Kirromycin Biosynthesis: Deciphering the Role of Genes
      Involved in Ethylmalonyl-CoA Supply and Tailoring Reactions.
AB  - Kirromycin is the main product of the soil-dwelling Streptomyces collinus Tu 365.
      The elucidation of the biosynthetic pathway revealed that the antibiotic is
      synthesised via a unique combination of trans-/cis-AT type I polyketide synthases
      and non-ribosomal peptide synthetases (PKS I/NRPS). This was the first example of
      an assembly line integrating the three biosynthetic principles in one pathway.
      However, information about other enzymes involved in kirromycin biosynthesis
      remained scarce. In this study, genes encoding tailoring enzymes KirM, KirHVI,
      KirOI, and KirOII, and the putative crotonyl-CoA reductase/carboxylase KirN were
      deleted, complemented, and the emerged products analysed by HPLC-HRMS and MS/MS.
      Derivatives were identified in mutants DeltakirM, DeltakirHVI, DeltakirOI, and
      DeltakirOII. The products of DeltakirOI, DeltakirOII, and kirHVI were subjected
      to 2D-NMR for structure elucidation. Our results enabled functional assignment of
      those enzymes, demonstrating their involvement in kirromycin tailoring. In the
      DeltakirN mutant, the production of kirromycin was significantly decreased. The
      obtained data enabled us to clarify the putative roles of the studied enzymes,
      ultimately allowing us to fill many of the missing gaps in the biosynthesis of
      the complex antibiotic. Furthermore, this collection of mutants can serve as a
      toolbox for generation of new kirromycins.

PMID- 29459766
TI  - Greater corneal nerve loss at the inferior whorl is related to the presence of
      diabetic neuropathy and painful diabetic neuropathy.
AB  - We assessed whether a measure of more distal corneal nerve fibre loss at the
      inferior whorl(IW) region is better than proximal measures of central corneal
      nerve damage in relation to the diagnosis of diabetic peripheral neuropathy(DPN),
      painful DPN and quality of life(QoL). Participants underwent detailed assessment
      of neuropathy, QoL using the SF36 questionnaire, pain visual analogue score(VAS),
      and corneal confocal microscopy(CCM). Corneal nerve fibre density (CNFD), branch
      density (CNBD) and length (CNFL) at the central cornea and inferior whorl length
      (IWL) and average(ANFL) and total(TNFL) nerve fibre length were compared in
      patients with and without DPN and between patients with and without painful DPN
      and in relation to QoL. All CCM parameters were significantly reduced, but IWL
      was reduced ~three-fold greater than CNFL in patients with and without DPN
      compared to controls. IWL(p = 0.001), ANFL(p = 0.01) and TNFL(p = 0.02) were
      significantly lower in patients with painful compared to painless DPN. The VAS
      score correlated with IWL(r = -0.36, P = 0.004), ANFL(r = -0.32, P = 0.01) and
      TNFL(r = -0.32, P = 0.01) and QoL correlated with CNFL(r = 0.35, P = 0.01) and
      IWL(r = 0.4, P = 0.004). Corneal nerve fibre damage is more prominent at the IW,
      lower in patients with painful compared to painless neuropathy and relates to
      their QoL. IWL may provide additional clinical utility for CCM in patients with
      DPN.

PMID- 29459767
TI  - Mcl-1 and Bcl-xL sequestration of Bak confers differential resistance to BH3-only
      proteins.
AB  - The prosurvival Bcl-2 family proteins Mcl-1 and Bcl-xL inhibit apoptosis by
      sequestering BH3-only proteins such as Bid and Bim (MODE 1) or the effector
      proteins Bak and Bax (MODE 2). To better understand the contributions of MODE 1
      and MODE 2 in blocking cell death, and thus how to bypass resistance to cell
      death, we examined prescribed mixtures of Bcl-2 family proteins. In a Bim and Bak
      mixture, Bcl-xL and Mcl-1 each sequestered not only Bim but also Bak as it became
      activated by Bim. In contrast, in a Bid and Bak mixture, Bcl-xL preferentially
      sequestered Bid while Mcl-1 preferentially sequestered Bak. Notably, Bcl-xL could
      sequester Bak in response to the BH3 mimetic ABT-737, despite this molecule
      targeting Bcl-xL. These findings highlight the importance of Bak sequestration in
      resistance to anti-cancer treatments, including BH3 mimetics.

PMID- 29459768
TI  - Oncoprotein Tudor-SN is a key determinant providing survival advantage under DNA
      damaging stress.
AB  - Herein, Tudor-SN was identified as a DNA damage response (DDR)-related protein
      that plays important roles in the early stage of DDR. X-ray or laser irradiation
      could evoke the accumulation of Tudor-SN to DNA damage sites in a poly(ADP
      ribosyl)ation-dependent manner via interaction with PARP-1. Additionally, we
      illustrated that the SN domain of Tudor-SN mediated the association of these two
      proteins. The accumulated Tudor-SN further recruited SMARCA5 (ATP-dependent
      chromatin remodeller) and GCN5 (histone acetyltransferase) to DNA damage sites,
      resulting in chromatin relaxation, and consequently activating the ATM kinase and
      downstream DNA repair signalling pathways to promote cell survival. Consistently,
      the loss-of-function of Tudor-SN attenuated the enrichment of SMARCA5, GCN5 and
      acetylation of histone H3 (acH3) at DNA break sites and abolished chromatin
      relaxation; as a result, the cells exhibited DNA repair and cell survival
      deficiency. As Tudor-SN protein is highly expressed in different tumours, it is
      likely to be involved in the radioresistance of cancer treatment.

PMID- 29459770
TI  - Polycomb protein family member CBX7 regulates intrinsic axon growth and
      regeneration.
AB  - Neurons in the central nervous system (CNS) lose their intrinsic ability and fail
      to regenerate, but the underlying mechanisms are largely unknown. Polycomb group
      (PcG) proteins, which include PRC1 and PRC2 complexes function as gene repressors
      and are involved in many biological processes. Here we report that PRC1
      components (polycomb chromobox (CBX) 2, 7, and 8) are novel regulators of axon
      growth and regeneration. Especially, knockdown of CBX7 in either embryonic
      cortical neurons or adult dorsal root ganglion (DRG) neurons enhances their axon
      growth ability. Two important transcription factors GATA4 and SOX11 are
      functional downstream targets of CBX7 in controlling axon regeneration. Moreover,
      knockdown of GATA4 or SOX11 in cultured DRG neurons inhibits axon regeneration
      response from CBX7 downregulation in DRG neurons. These findings suggest that
      targeting CBX signaling pathway may be a novel approach for promoting the
      intrinsic regenerative capacity of damaged CNS neurons.

PMID- 29459769
TI  - Exploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD.
AB  - Although amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease,
      was first described in 1874, a flurry of genetic discoveries in the last 10 years
      has markedly increased our understanding of this disease. These findings have not
      only enhanced our knowledge of mechanisms leading to ALS, but also have revealed
      that ALS shares many genetic causes with another neurodegenerative disease,
      frontotemporal lobar dementia (FTLD). In this review, we survey how recent
      genetic studies have bridged our mechanistic understanding of these two related
      diseases and how the genetics behind ALS and FTLD point to complex disorders,
      implicating non-neuronal cell types in disease pathophysiology. The involvement
      of non-neuronal cell types is consistent with a non-cell autonomous component in
      these diseases. This is further supported by studies that identified a critical
      role of immune-associated genes within ALS/FTLD and other neurodegenerative
      disorders. The molecular functions of these genes support an emerging concept
      that various non-autonomous functions are involved in neurodegeneration. Further
      insights into such a mechanism(s) will ultimately lead to a better understanding
      of potential routes of therapeutic intervention. Facts ALS and FTLD are severe
      neurodegenerative disorders on the same disease spectrum. Multiple cellular
      processes including dysregulation of RNA homeostasis, imbalance of proteostasis,
      contribute to ALS/FTLD pathogenesis. Aberrant function in non-neuronal cell
      types, including microglia, contributes to ALS/FTLD. Strong neuroimmune and
      neuroinflammatory components are associated with ALS/FTLD patients. Open
      Questions Why can patients with similar mutations have different disease
      manifestations, i.e., why do C9ORF72 mutations lead to motor neuron loss in some
      patients while others exhibit loss of neurons in the frontotemporal lobe? Do ALS
      causal mutations result in microglial dysfunction and contribute to ALS/FTLD
      pathology? How do microglia normally act to mitigate neurodegeneration in
      ALS/FTLD? To what extent do cellular signaling pathways mediate non-cell
      autonomous communications between distinct central nervous system (CNS) cell
      types during disease? Is it possible to therapeutically target specific cell
      types in the CNS?

PMID- 29459771
TI  - Lactobacillus accelerates ISCs regeneration to protect the integrity of
      intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs
      secretion of IL-22.
AB  - The regeneration of intestinal epithelial are maintained by continuous
      differentiation and proliferation of intestinal stem cells (ISCs) under
      physiological and pathological conditions. However, little is known about the
      regulatory effect of intestinal microbiota on its recovery ability to repair
      damaged mucosal barrier. In this study, we established intestinal organoids and
      lamina propria lymphocytes (LPLs) co-cultured system, plus mice experiments, to
      explore the protective effect of Lactobacillus reuteri D8 on integrity of
      intestinal mucosa. We found that only live L. reuteri D8 was effective in
      protecting the morphology of intestinal organoids and normal proliferation of
      epithelial stained with EdU under TNF-alpha treatment, which was also further
      verified in mice experiments. L. reuteri D8 colonized in the intestinal mucosa
      and ameliorated intestinal mucosa damage caused by DSS treatment, including
      improvement of body weight, colon length, pathological change, and proliferation
      level. The repair process stimulated by L. reuteri D8 was also accompanied with
      increased numbers of Lgr5+ and lysozyme+ cells both in intestinal organoids and
      mice intestine. Furthermore, we demonstrated that D8 metabolite indole-3-aldehyde
      stimulated LPLs to secret IL-22 through aryl hydrocarbon receptor (AhR) and then
      induced phosphorylation of STAT3 to accelerate proliferation of intestinal
      epithelial, thus recovering damaged intestinal mucosa. Our findings indicate L.
      reuteri protects intestinal barrier and activates intestinal epithelial
      proliferation, which sheds light on treatment approaches for intestinal
      inflammation based on ISCs with probiotics Lactobacillus and daily probiotic
      consumption in heath foods.

PMID- 29459772
TI  - Monoamine oxidase-dependent endoplasmic reticulum-mitochondria dysfunction and
      mast cell degranulation lead to adverse cardiac remodeling in diabetes.
AB  - Monoamine oxidase (MAO) inhibitors ameliorate contractile function in diabetic
      animals, but the mechanisms remain unknown. Equally elusive is the interplay
      between the cardiomyocyte alterations induced by hyperglycemia and the
      accompanying inflammation. Here we show that exposure of primary cardiomyocytes
      to high glucose and pro-inflammatory stimuli leads to MAO-dependent increase in
      reactive oxygen species that causes permeability transition pore opening and
      mitochondrial dysfunction. These events occur upstream of endoplasmic reticulum
      (ER) stress and are abolished by the MAO inhibitor pargyline, highlighting the
      role of these flavoenzymes in the ER/mitochondria cross-talk. In vivo,
      streptozotocin administration to mice induced oxidative changes and ER stress in
      the heart, events that were abolished by pargyline. Moreover, MAO inhibition
      prevented both mast cell degranulation and altered collagen deposition, thereby
      normalizing diastolic function. Taken together, these results elucidate the
      mechanisms underlying MAO-induced damage in diabetic cardiomyopathy and provide
      novel evidence for the role of MAOs in inflammation and inter-organelle
      communication. MAO inhibitors may be considered as a therapeutic option for
      diabetic complications as well as for other disorders in which mast cell
      degranulation is a dominant phenomenon.

PMID- 29459773
TI  - Erythrocyte glutathione transferase in kidney transplantation: a probe for kidney
      detoxification efficiency.
AB  - Erythrocyte glutathione transferase (e-GST) is overexpressed in case of increased
      blood toxicity and its level correlates with the kidney disease progression.
      Thus, it represents a probe of kidney efficiency against circulating toxins. We
      measured the activity of e-GST in patients with transplant kidney from living and
      cadaver donors, correlated its level to biochemical parameters of kidney
      function, and measured the level of oxidized albumin as a probe of oxidative
      stress using a new simple procedure. Interestingly, the activity of e-GST in
      transplant patients from cadaver donors (N = 153) is very high (11.7 U/gHb)
      compared to healthy subjects (N = 80) ( 5.6 U/gHb). Lower values were observed in
      transplant patients with kidney from living donors (N = 16) (9.8 U/gHb). Except
      for steroids, no correlation has been found with the immunosuppressive therapies
      and routine clinical and laboratory parameters. Also serum oxidized albumin,
      which reveals oxidative stress, is significantly higher in transplant patients
      from cadaver donors (53%) compared to that from living donors (36%). Overall,
      these data indicate that most of transplant kidneys from cadavers lost part of
      the detoxifying power against circulating toxins and suffer a relevant oxidative
      stress compared to those coming from living donors. A case report suggests that e
      GST could represent a very early marker of incipient graft rejection. In
      conclusion, e-GST may be used to check the decline or maintenance of the kidney
      detoxification competence during post-transplantation course.

PMID- 29459774
TI  - Nonylphenol aggravates non-alcoholic fatty liver disease in high sucrose-high fat
      diet-treated rats.
AB  - Exposure to environmental endocrine disruptors (EEDs) contributes to the
      pathogenesis of many metabolic disorders. Here, we have analyzed the effect of
      the EED-nonylphenol (NP) on the promotion of non-alcoholic fatty liver disease
      (NAFLD) in rats fed high sucrose-high fat diet (HSHFD). Fifty Sprague-Dawley rats
      were divided into five groups: controls fed a normal diet (C-ND); HSHFD-fed
      controls (C-HSHFD); and rats fed a HSHFD combined with NP at doses of 0.02
      MUg/kg/day (NP-L-HSHFD), 0.2 MUg/kg/day (NP-M-HSHFD), and 2 MUg/kg/day (NP-H
      HSHFD). Subchronic exposure to NP coupled with HSHFD increased daily water and
      food intake (p < 0.05), hepatic echogenicity and oblique liver diameter (p <
      0.05), and plasma levels of alanine aminotransferase, aspartate aminotransferase,
      total cholesterol, triglycerides, and low density lipoprotein cholesterol (p <
      0.05). Combined exposure to NP and HSHFD induced macrovesicular steatosis with
      dilation and congestion of the central vein, liver inflammatory cell
      infiltration, and expression of genes regulating lipid metabolism, SREBP-1C, FAS,
      and Ucp2. These results demonstrate that NP aggravates NAFLD in HSHFD-treated
      rats by up-regulating lipogenic genes, and that HSHFD increases the toxic effects
      of NP. Thus subchronic NP exposure may lead to NAFLD, especially when combined
      with a high-sucrose/high-fat diet.

PMID- 29459776
TI  - Antibodies in children with malaria to PfEMP1, RIFIN and SURFIN expressed at the
      Plasmodium falciparum parasitized red blood cell surface.
AB  - Naturally acquired antibodies to proteins expressed on the Plasmodium falciparum
      parasitized red blood cell (pRBC) surface steer the course of a malaria infection
      by reducing sequestration and stimulating phagocytosis of pRBC. Here we have
      studied a selection of proteins representing three different parasite gene
      families employing a well-characterized parasite with a severe malaria phenotype
      (FCR3S1.2). The presence of naturally acquired antibodies, impact on rosetting
      rate, surface reactivity and opsonization for phagocytosis in relation to
      different blood groups of the ABO system were assessed in a set of sera from
      children with mild or complicated malaria from an endemic area. We show that the
      naturally acquired immune responses, developed during malaria natural infection,
      have limited access to the pRBCs inside a blood group A rosette. The data also
      indicate that SURFIN4.2 may have a function at the pRBC surface, particularly
      during rosette formation, this role however needs to be further validated. Our
      results also indicate epitopes differentially recognized by rosette-disrupting
      antibodies on a peptide array. Antibodies towards parasite-derived proteins such
      as PfEMP1, RIFIN and SURFIN in combination with host factors, essentially the ABO
      blood group of a malaria patient, are suggested to determine the outcome of a
      malaria infection.

PMID- 29459778
TI  - Effects of dipolar interactions on the sensitivity of nonlinear spinor-BEC
      interterometry.
AB  - We consider the effects of dipole-dipole interactions on a nonlinear
      interferometer with spin-1 Bose-Einstein condensates. Compared with the
      traditional atomic SU(1,1) interferometer, the shot-noise phase sensitivity can
      be beaten with respect to the input total average number of particles; and the
      improved sensitivity depends on the effective strength of the dipolar interaction
      via modifying the trapping geometry. It indicates that the best performance of
      the interferometer is achieved with highly oblate trap potential. The Bayesian
      phase estimation strategy is explored to extract the phase information. We show
      that the Cramer-Rao phase uncertainly bound can saturate, when the ideal dis
      entangle scheme is applied. The phase average of the phase sensitivity is also
      discussed.

PMID- 29459777
TI  - Ceramic Microbial Fuel Cells Stack: power generation in standard and
      supercapacitive mode.
AB  - In this work, a microbial fuel cell (MFC) stack containing 28 ceramic MFCs was
      tested in both standard and supercapacitive modes. The MFCs consisted of carbon
      veil anodes wrapped around the ceramic separator and air-breathing cathodes based
      on activated carbon catalyst pressed on a stainless steel mesh. The anodes and
      cathodes were connected in parallel. The electrolytes utilized had different
      solution conductivities ranging from 2.0 mScm-1 to 40.1 mScm-1, simulating
      diverse wastewaters. Polarization curves of MFCs showed a general enhancement in
      performance with the increase of the electrolyte solution conductivity. The
      maximum stationary power density was 3.2 mW (3.2 Wm-3) at 2.0 mScm-1 that
      increased to 10.6 mW (10.6 Wm-3) at the highest solution conductivity (40.1 mScm
      1). For the first time, MFCs stack with 1 L operating volume was also tested in
      supercapacitive mode, where full galvanostatic discharges are presented. Also in
      the latter case, performance once again improved with the increase in solution
      conductivity. Particularly, the increase in solution conductivity decreased
      dramatically the ohmic resistance and therefore the time for complete discharge
      was elongated, with a resultant increase in power. Maximum power achieved varied
      between 7.6 mW (7.6 Wm-3) at 2.0 mScm-1 and 27.4 mW (27.4 Wm-3) at 40.1 mScm-1.

PMID- 29459775
TI  - Formalising recall by genotype as an efficient approach to detailed phenotyping
      and causal inference.
AB  - Detailed phenotyping is required to deepen our understanding of the biological
      mechanisms behind genetic associations. In addition, the impact of potentially
      modifiable risk factors on disease requires analytical frameworks that allow
      causal inference. Here, we discuss the characteristics of Recall-by-Genotype
      (RbG) as a study design aimed at addressing both these needs. We describe two
      broad scenarios for the application of RbG: studies using single variants and
      those using multiple variants. We consider the efficacy and practicality of the
      RbG approach, provide a catalogue of UK-based resources for such studies and
      present an online RbG study planner.

PMID- 29459779
TI  - Small molecule metabolite biomarkers for hepatocellular carcinoma with bile duct
      tumor thrombus diagnosis.
AB  - Hepatocellular carcinoma with bile duct tumor thrombus (BDTT) is a malignant
      disease. The most commonly used diagnosis methods for BDTT are MRCP/ERCP,
      ultrasonic diagnosis or CT scan. However, BDTT is often misdiagnosed as other
      bile duct diseases, such as extrahepatic cholangiocarcinoma (EHCC), choledochal
      cyst (Cyst) and common bile duct stone (Stone). Diagnostic methods, which are
      more accurate and less destructive, are urgently needed. In this paper, we
      analyzed the small molecule metabolites in the serum of BDTT, Stone, Cyst and
      EHCC patients and normal people using untargeted GC-MS, and identified 21
      metabolites that show different levels among different samples. Using targeted
      UHPLC-QQQ-MS analysis, we found that several metabolites are significantly
      changed. ROC curve analysis revealed two metabolites, L-citrulline and D-aspartic
      acid, as potential biomarkers that can distinguish BDTT from other bile duct
      diseases.

PMID- 29459781
TI  - RIPK1-mediated induction of mitophagy compromises the viability of extracellular
      matrix-detached cells.
AB  - For cancer cells to survive during extracellular matrix (ECM) detachment, they
      must inhibit anoikis and rectify metabolic deficiencies that cause non-apoptotic
      cell death. Previous studies in ECM-detached cells have linked non-apoptotic cell
      death to reactive oxygen species (ROS) generation, although the mechanistic
      underpinnings of this link remain poorly defined. Here, we uncover a role for
      receptor-interacting protein kinase 1 (RIPK1) in the modulation of ROS and cell
      viability during ECM detachment. We find that RIPK1 activation during ECM
      detachment results in mitophagy induction through a mechanism dependent on the
      mitochondrial phosphatase PGAM5. As a consequence of mitophagy, ECM-detached
      cells experience diminished NADPH production in the mitochondria, and the
      subsequent elevation in ROS levels leads to non-apoptotic death. Furthermore, we
      find that antagonizing RIPK1/PGAM5 enhances tumour formation in vivo. Thus, RIPK1
      mediated induction of mitophagy may be an efficacious target for therapeutics
      aimed at eliminating ECM-detached cancer cells.

PMID- 29459782
TI  - Distinct macular thickness changes after femtosecond laser-assisted cataract
      surgery of age-related cataract and myopia with cataract.
AB  - Cataract surgery can cause macular thickness change. We used optical coherence
      tomography (OCT) to assess the macular thickness of different regions after
      femtosecond laser-assisted cataract surgery of age-related cataracts (ARC) and
      myopia cases with cataract (myopia group). Fifty eyes of 50 patients in ARC group
      and fifty eyes of 50 patients in myopia with cataract group were included. All
      study underwent femtosecond laser-assisted cataract surgery and macular thickness
      of was measured at pre-operation and 1 week, 1 month after surgery. There are
      significant differences of foveal thickness (P = 0.02), foveal volume (P = 0.02)
      and average retinal thickness (P = 0.02) between two groups before operation. In
      the myopia group, statistically significant differences were not found in
      postoperative macular thickness as compared with ARC group. There are differences
      in macular thickness between pre-operation and 1 month after operation when
      compared with nasal outer macular ring thickness (P = 0.022), foveal volume (P =
      0.005) and average retinal thickness (P = 0.012) in ARC group. The study suggest
      that femtosecond laser-assisted cataract extraction is safe in myopia group that
      did not cause significant increase of macular thickness. However, an increased
      post-operative local macular thickness was recoded while comparing macular
      thickness with the baseline in ARC group.

PMID- 29459783
TI  - Nanodiamonds for device applications: An investigation of the properties of boron
      doped detonation nanodiamonds.
AB  - The inclusion of boron within nanodiamonds to create semiconducting properties
      would create a new class of applications in the field of nanodiamond electronics.
      Theoretical studies have differed in their conclusions as to whether nm-scale NDs
      would support a stable substitutional boron state, or whether such a state would
      be unstable, with boron instead aggregating or attaching to edge structures. In
      the present study detonation-derived NDs with purposefully added boron during the
      detonation process have been studied with a wide range of experimental
      techniques. The DNDs are of ~4 nm in size, and have been studied with CL, PL,
      Raman and IR spectroscopies, AFM and HR-TEM and electrically measured with
      impedance spectroscopy; it is apparent that the B-DNDs studied here do indeed
      support substitutional boron species and hence will be acting as semiconducting
      diamond nanoparticles. Evidence for moderate doping levels in some particles
      (~1017 B cm-3), is found alongside the observation that some particles are
      heavily doped (~1020 B cm-3) and likely to be quasi-metallic in character. The
      current study has therefore shown that substitutional boron doping in nm NDs is
      in fact possible, opening-up the path to a whole host of new applications for
      this interesting class of nano-particles.

PMID- 29459780
TI  - Identification of distinct nanoparticles and subsets of extracellular vesicles by
      asymmetric flow field-flow fractionation.
AB  - The heterogeneity of exosomal populations has hindered our understanding of their
      biogenesis, molecular composition, biodistribution and functions. By employing
      asymmetric flow field-flow fractionation (AF4), we identified two exosome
      subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles,
      Exo-S, 60-80 nm) and discovered an abundant population of non-membranous
      nanoparticles termed 'exomeres' (~35 nm). Exomere proteomic profiling revealed an
      enrichment in metabolic enzymes and hypoxia, microtubule and coagulation proteins
      as well as specific pathways, such as glycolysis and mTOR signalling. Exo-S and
      Exo-L contained proteins involved in endosomal function and secretion pathways,
      and mitotic spindle and IL-2/STAT5 signalling pathways, respectively. Exo-S, Exo
      L and exomeres each had unique N-glycosylation, protein, lipid, DNA and RNA
      profiles and biophysical properties. These three nanoparticle subsets
      demonstrated diverse organ biodistribution patterns, suggesting distinct
      biological functions. This study demonstrates that AF4 can serve as an improved
      analytical tool for isolating extracellular vesicles and addressing the
      complexities of heterogeneous nanoparticle subpopulations.

PMID- 29459784
TI  - 2'-O-methylation in mRNA disrupts tRNA decoding during translation elongation.
AB  - Chemical modifications of mRNA may regulate many aspects of mRNA processing and
      protein synthesis. Recently, 2'-O-methylation of nucleotides was identified as a
      frequent modification in translated regions of human mRNA, showing enrichment in
      codons for certain amino acids. Here, using single-molecule, bulk kinetics and
      structural methods, we show that 2'-O-methylation within coding regions of mRNA
      disrupts key steps in codon reading during cognate tRNA selection. Our results
      suggest that 2'-O-methylation sterically perturbs interactions of ribosomal
      monitoring bases (G530, A1492 and A1493) with cognate codon-anticodon helices,
      thereby inhibiting downstream GTP hydrolysis by elongation factor Tu (EF-Tu) and
      A-site tRNA accommodation, leading to excessive rejection of cognate
      aminoacylated tRNAs in initial selection and proofreading. Our current and prior
      findings highlight how chemical modifications of mRNA tune the dynamics of
      protein synthesis at different steps of translation elongation.

PMID- 29459785
TI  - GlcNAc-1-P-transferase-tunicamycin complex structure reveals basis for inhibition
      of N-glycosylation.
AB  - N-linked glycosylation is a predominant post-translational modification of
      protein in eukaryotes, and its dysregulation is the etiology of several human
      disorders. The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N
      acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the
      first and committed step of N-linked glycosylation in the endoplasmic reticulum
      membrane, and it is the target of the natural product tunicamycin. Tunicamycin
      has potent antibacterial activity, inhibiting the bacterial cell wall synthesis
      enzyme MraY, but its usefulness as an antibiotic is limited by off-target
      inhibition of human GPT. Our understanding of how tunicamycin inhibits N-linked
      glycosylation and efforts to selectively target MraY are hampered by a lack of
      structural information. Here we present crystal structures of human GPT in
      complex with tunicamycin. Structural and functional analyses reveal the
      difference between GPT and MraY in their mechanisms of inhibition by tunicamycin.
      We demonstrate that this difference could be exploited to design MraY-specific
      inhibitors as potential antibiotics.

PMID- 29459786
TI  - Are 'fruits and vegetables' intake really what they seem in India?
AB  - BACKGROUND/OBJECTIVES: Fruits and vegetables are integral parts of a healthy
      diet. This study evaluated the quantity and diversity of the fruit and vegetable
      intake in India, with a focus on its distribution across sectors and wealth
      quintiles. SUBJECTS/METHODS: A secondary data analysis on the nation-wide NSSO
      Household Consumer Expenditure Survey 2011-2012 was performed to estimate the
      amount (g/capita/day) and diversity of household intake of fruits and vegetables
      in the rural and the urban sectors of India. Using the expenditure data,
      households in both the sectors were further divided into wealth quintiles and
      differences in the diversity of intake was evaluated across these quintiles
      separately for each sector. RESULTS: The per capita household vegetable and fruit
      intake was found to be 145 and 15 g, respectively, for rural India, and 155 and
      29 g for urban India. A significant portion of this intake came from energy-dense
      food items; potatoes and bananas for vegetable and fruit intake respectively.
      Further, while wealth marginally improved the diversity in vegetable intake, no
      such trend was observed in fruit intake. CONCLUSIONS: Given the high proportion
      of energy-dense fruits and vegetables in the Indian total intake, the focus
      should be on improving the diversity of vegetables, as well as on increasing the
      intake and diversity of fruits.

PMID- 29459787
TI  - Nutritional risk screening score is an independent predictive factor of
      anastomotic leakage after rectal cancer surgery.
AB  - BACKGROUND/OBJECTIVES: Nutritional risk screening (NRS) score has been reported
      as a predictor of postoperative outcomes in patients undergoing abdominal
      surgery, although the correlation between NRS and anastomotic leakage (AL) after
      rectal cancer surgery is uncertain. This study aimed to evaluate the association
      between NRS score and AL following rectal cancer surgery. SUBJECT/METHODS: We
      retrospectively reviewed data of rectal cancer patients from a tertiary referral
      center in South Korea, and included 1063 patients with primary rectal cancer who
      underwent sphincter-preserving surgery between January 2011 and December 2015. We
      utilized the Chonnam National University Hwasun Hospital-Nutritional Risk
      Screening Tool (CNUHH-NRST), which was developed and cross-validated on the basis
      of the NRS 2002 and MST, as a screening tool of nutritional risk. Patients with
      NRS scores >=4 were compared with those with NRS scores <4, and the risk factors
      for AL were analyzed. RESULTS: One-hundred-nineteen (11.2%) patients had high
      nutritional risk (NRS score >=4). The patients with a nutritional risk had more
      advanced tumor stages than those without nutritional risk. AL occurred in 69
      (6.5%) patients. The multivariate logistic regression analysis showed high
      American Society of Anesthesiologists score (odds ratio (OR) = 2.435, 95%
      confidence interval (CI) = 1.085-5.469), long operative time (OR = 1.975, 95% CI
      = 1.177-3.313), and high NRS score (OR = 2.044, 95% CI = 1.085-3.851) as
      independent risk factors of AL. CONCLUSIONS: The NRS score was an independent
      predictive factor of AL after rectal cancer surgery. Patients with nutritional
      risks who require rectal cancer surgery should be carefully managed.

PMID- 29459788
TI  - Balloon-assisted ultrasonic localization: a novel technique for direct
      percutaneous endoscopic jejunostomy.
AB  - Direct percutaneous endoscopic jejunostomy (DPEJ) is a useful method for the
      establishment of enteral nutrition (EN) pathway. However, the identification of
      stomal puncture points for DPEJ is difficult. Here we present a case treated with
      an improved technique for DPEJ puncture-point localization, which was named DPEJ
      with balloon-assisted ultrasonic localization (DPEJ-BAUL). There were four steps
      after insertion of an endoscope into the jejunum: (1) a balloon dilatation
      catheter was inserted through the endoscope working channel; (2) the balloon was
      fully filled with water; (3) the site of puncture was selected with an ultrasonic
      probe percutaneously locating the water-filled balloon; and (4) a jejunostomy
      tube was placed by introducer technique. Rapid localization of a puncture site
      was possible with BAUL and the DPEJ procedure was successful. The patient's
      nutritional status was improved with EN and no postoperative complications were
      observed. DPEJ-BAUL is a feasible and effective technique to increase the
      technical success rate of DPEJ in patients with negative transillumination test
      results.

PMID- 29459789
TI  - Retrospective observational cohort study regarding the effect of breastfeeding on
      challenge-proven food allergy.
AB  - BACKGROUND/OBJECTIVES: Human breast milk is generally regarded as the best
      nutrition for infants in their first months of life. Whether breastfeeding has a
      protective effect on food allergy is a point of debate and the subject of this
      study. SUBJECTS/METHODS: This retrospective study was conducted in 649 children
      who underwent a double-blind placebo-controlled food challenge (DBPCFC) as part
      of routine care in a tertiary care clinic. Food allergy was defined as having at
      least one positive DBPCFC to any food. The association between both "any"
      breastfeeding (yes/no) and its duration in months with food allergy was studied
      by logistic regression analysis with correction for confounding variables.
      RESULTS: The prevalence of food allergy was 58.9% (n = 382). Of all subjects,
      75.8% (n = 492) was breastfed and 24.2% (n = 157) bottle-fed. There was no
      significant association between food allergy and breastfeeding versus bottle
      feeding after correction for the confounding effect of increased breastfeeding by
      atopic parents and a history of asthma in the child (OR = 1.24, 95% CI = 0.85
      1.79, p = 0.27). However, in breastfed children, every additional month of
      breastfeeding lowered the risk for food allergy by ~4% (OR = 0.96, 95% CI = 0.93
      0.99, p = 0.02). No confounders were identified in this association. CONCLUSION:
      These results show for the first time that in children investigated for possible
      food allergy, every additional month of breastfeeding is associated with a lower
      risk of developing clinical food allergy as diagnosed by DBPCFC. However,
      overall, there was no association between the prevalence of food allergy and
      breastfeeding versus bottle-feeding in this tertiary care population.

PMID- 29459790
TI  - The simplified nutrient profiling system (SENS) adequately ranks foods in
      relation to the overall nutritional quality of diets: a validation study.
AB  - BACKGROUND/OBJECTIVES: We aimed to validate the simplified nutrient profiling
      system (SENS) algorithm based on its ability to rank foods across the four SENS
      classes in relation to overall nutritional quality of both observed diets and
      nutritionally optimized diets. SUBJECTS/METHODS: Foods and beverages from the
      French nutritional composition database were classified according to SENS. Diets
      consumed by French adults in the latest national dietary survey (>19 years, n =
      1719) were divided into four nutritional quality levels, and average daily
      frequencies (number of portions per day) of foods from the four SENS classes were
      compared between the four levels. Then, for each individual observed diet, one
      iso-caloric and nutritionally adequate diet was optimized, and variations in
      daily frequencies of foods from each SENS class between observed and optimized
      diets were estimated. RESULTS: In observed diets, as overall nutritional quality
      level of diet increased, daily frequency increased for Class-1 foods (3.5 to 8.7
      portions/d) and decreased for Class-4 foods (6.8 to 3.0 portions/day). From
      observed to optimized diets, daily frequency increased for Class-1 foods for
      98.4% of individuals and decreased for Class-4 foods for 94.2% of individuals.
      Class-2 and Class-3 foods also followed patterns that fit the expected ranking.
      CONCLUSIONS: Results from two WHO-recommended validation approaches showed that
      the SENS algorithm adequately ranks foods according to their contribution to
      overall nutritional quality of diets, which is a pre-requisite to use for
      simplified nutritional labeling in Europe.

PMID- 29459791
TI  - Different enteral nutrition formulas have no effect on glucose homeostasis but on
      diet-induced thermogenesis in critically ill medical patients: a randomized
      controlled trial.
AB  - BACKGROUND/OBJECTIVES: Hyperglycemia is common in critically ill patients and
      associated with increased mortality. It has been suggested that different
      nutrition formulas may beneficially influence glucose levels in surgical
      intensive care patients. In this prospective randomized clinical cohort study we
      investigated glucose homeostasis in response to different enteral nutrition
      formulas in medical critically ill patients. SUBJECTS/METHODS: 60 medical
      critically ill patients were randomized to receive continuous fat-based (group A,
      n = 30) or glucose-based enteral nutrition (group B, n = 30) for seven days.
      Indirect calorimetry was performed to determine energy demand at baseline and on
      days 3 and 7. Glucose levels and area under the curve (AUC), insulin demand,
      glucose variability, and calorie and substrate intake per 24 h were assessed for
      7 days. RESULTS: Over the course of 7 days patients had similar average daily
      glucose (p = 0.655), glucose AUC (A: 758 (641-829) mg/dl/day vs B: 780 (733-845)
      mg/dl/day, p = 0.283), similar overall insulin demand (A: 153.5 (45.3-281.5) IE
      vs B: 167.9 (82.3-283.8) IE, p = 0.525), and received similar amounts of enteral
      nutrition per 24 h. Resting energy expenditure was similar at baseline (A: 1556
      (1227-1808) kcal/day vs B: 1563 (1306-1789) kcal/day, p = 0.882) but energy
      expenditure increased substantially over time in group A (p < 0.0001), but not in
      group B (p = 0.097). CONCLUSION: Fat-based and glucose-based EN influence glucose
      homeostasis and insulin demand similarly, yet diet-induced thermogenesis was
      substantially higher in critically ill patients receiving fat-based enteral
      nutrition.

PMID- 29459793
TI  - Consequences of SPAK inactivation on Hyperkalemic Hypertension caused by WNK1
      mutations: evidence for differential roles of WNK1 and WNK4.
AB  - Mutations of the gene encoding WNK1 [With No lysine (K) kinase 1] or WNK4 cause
      Familial Hyperkalemic Hypertension (FHHt). Previous studies have shown that the
      activation of SPAK (Ste20-related Proline/Alanine-rich Kinase) plays a dominant
      role in the development of FHHt caused by WNK4 mutations. The implication of SPAK
      in FHHt caused by WNK1 mutation has never been investigated. To clarify this
      issue, we crossed WNK1+/FHHt mice with SPAK knock-in mice in which the T-loop
      Thr243 residue was mutated to alanine to prevent activation by WNK kinases. We
      show that WNK1+/FHHT:SPAK 243A/243A mice display an intermediate phenotype,
      between that of control and SPAK 243A/243A mice, with normal blood pressure but
      hypochloremic metabolic alkalosis. NCC abundance and phosphorylation levels also
      decrease below the wild-type level in the double-mutant mice but remain higher
      than in SPAK 243A/243A mice. This is different from what was observed in WNK4
      FHHt mice in which SPAK inactivation completely restored the phenotype and NCC
      expression to wild-type levels. Although these results confirm that FHHt caused
      by WNK1 mutations is dependent on the activation of SPAK, they suggest that WNK1
      and WNK4 play different roles in the distal nephron.

PMID- 29459792
TI  - C-terminal calcium binding of alpha-synuclein modulates synaptic vesicle
      interaction.
AB  - Alpha-synuclein is known to bind to small unilamellar vesicles (SUVs) via its N
      terminus, which forms an amphipathic alpha-helix upon membrane interaction. Here
      we show that calcium binds to the C terminus of alpha-synuclein, therewith
      increasing its lipid-binding capacity. Using CEST-NMR, we reveal that alpha
      synuclein interacts with isolated synaptic vesicles with two regions, the N
      terminus, already known from studies on SUVs, and additionally via its C
      terminus, which is regulated by the binding of calcium. Indeed, dSTORM on
      synaptosomes shows that calcium mediates the localization of alpha-synuclein at
      the pre-synaptic terminal, and an imbalance in calcium or alpha-synuclein can
      cause synaptic vesicle clustering, as seen ex vivo and in vitro. This study
      provides a new view on the binding of alpha-synuclein to synaptic vesicles, which
      might also affect our understanding of synucleinopathies.

PMID- 29459794
TI  - Impaired Cardiac Function in Patients with Multiple Sclerosis by Comparison with
      Normal Subjects.
AB  - Multiple sclerosis (MS), neurologic disease affecting young population, may cause
      cardiovascular dysfunction, due to autonomous nervous dysfunction, physical
      invalidity, increased oxidative stress, and systemic inflammatory status.
      However, cardiovascular function is rarely evaluated in these patients. We
      assessed left and right ventricular (LV and RV) function by 2D, 3D, tissue
      Doppler, and speckle tracking echocardiography, and vascular function by
      remodeling, stiffness, and endothelial dysfunction parameters in patients with
      MS, compared to control subjects. 103 subjects (35 +/- 10 years,70 women) were
      studied: 67 patients with MS and 36 control subjects. Patients with MS had
      decreased LV systolic function, confirmed by lower 2D and 3D ejection fraction,
      mitral annular plane systolic excursion, longitudinal myocardial systolic
      velocities, and 2D and 3D global longitudinal strain. The RV function was also
      decreased, as demonstrated by lower fractional area change, tricuspid annular
      plane systolic excursion, longitudinal systolic velocities, and longitudinal
      strain. Additionally, LV diastolic and left atrial (LA)  function were decreased
      compared to controls. The parameters of arterial and endothelial function were
      similar between groups. Patients with MS have impaired biventricular function by
      comparison with normal subjects, with reduced LA function, but normal arterial
      and endothelial function. The noninvasive echocardiographic techniques might help
      to determine patients with MS at risk of developing cardiovascular dysfunction.

PMID- 29459795
TI  - High sensitization efficiency and energy transfer routes for population inversion
      at low pump intensity in Er organic complexes for IR amplification.
AB  - Organic erbium complexes have long been of interest due to their potential for
      using the strong absorption into the organic to sensitise the erbium emission.
      Despite this interest there is remarkably little quantitative information on how
      effective the approach is and the discussion of the energy transfer mechanism is
      generally vague. Here we accurately quantify the sensitisation as a function of
      excitation pump density and model it using a rate equation approach. As a result,
      we can calculate the degree of population inversion for the erbium ions as a
      function of the pump intensity. We demonstrate that even when we increase the
      erbium concentration in the films from ~10 to ~80% we find a relatively small
      decrease in the sensitisation which we attribute to the large (>20 A) Forster
      radius for the sensitisation process. We show that we can obtain population
      inversion in our films at very low pump powers ~600 mW/cm2. The calculated
      Forster radius for the organic erbium complexes suggests design rules for energy
      transfer between antennas and erbium ions in molecular systems and hybrid organic
      inorganic nanoparticles.

PMID- 29459796
TI  - Correction: Genetic inhibition of neurotransmission reveals role of glutamatergic
      input to dopamine neurons in high-effort behavior.
AB  - In Figure 1e and f, "F4 control" should be "Cre/tdTomato" and "F4Cre KO" should
      be "F4Cre/tdTomato". In addition, in the Figure1f legend, the first sentence
      should end with "(Cre/tdTomato: n = 10, F4Cre/tdTomato: n = 14)".In the
      'Materials and Methods' section, under 'Electrophysiology,' the n values for
      evoked action potential recordings were omitted. The sentence 'For high-frequency
      stimulus-induced action potentials, the stimulus electrode was placed in the
      rostral part of VTA and a train of 100 Hz stimuli (1 s) was applied' should end
      with '(Cre/tdTomato: n=10, F4Cre/tdTomato: n=14).'Later in the same paragraph, in
      'For recording evoked EPSCs (Cre/tdTomato, n=13, F4Cre/tdTomato, n=15; AMPA EPSCs
      were recorded at -70  mV and NMDA EPSCs were recorded at +40 mV)', the phrase
      'Cre/tdTomato, n=13, F4Cre/tdTomato, n=15' should be deleted; those n values
      should have appeared at the end of the later sentence beginning 'Miniature
      ESPCs...'. The complete, corrected sentence is 'Miniature EPSCs (mEPSCs) were
      acquired in the presence of 0.5-1 MUM TTX and 100 MUM picrotoxin and
      semiautomatically detected by offline analysis using in-house software in Igor
      Pro (Wavemetrics, Portland, OR, USA) (Cre/tdTomato, n=13, F4Cre/tdTomato,
      n=15).'Finally, in the 'Materials and Methods' section, third sentence under
      'Immunohistochemistry,' information for one TH antibody was omitted. The list of
      antibodies should end with 'or Millipore MAB5280, 1:1000-1:2000.'

PMID- 29459797
TI  - [Endoscopic ultrasound: a look into the future].

PMID- 29459798
TI  - [Localization and size of colon adenomas as factors related to high
      gradedysplasia].
AB  - OBJECTIVE: To determine whether localization and size are related to the presence
      of high-grade dysplasia of colon adenomas in patients of a Peruvian hospital.
      MATERIALS AND METHODS: This is a descriptive transversal study. We checked
      colonoscopyreports of 2014-2015 years of Hospital Daniel Alcides Carrion, we
      included the polyps found in patients older than 18 years old, and excluded
      reports from patients with colorectal cancer, an antecedent of oncological
      surgery, inflammatory bowel disease and polyposis (6 or more). We used data based
      on localization (proximal and distal colon, based on the splenic angle), size
      (less than 10 mm and 10 mm or more), shape (pediculate and sessile) and grade of
      dysplasia (low and high-grade). We calculated the strength of association by OR,
      and we determined whether there was association by Chi-square test with a
      significance value less than 0.05. RESULTS: We reviewed a total of 1710 of
      colonoscopy reports, 378 patients had polyps, so the adenoma detection rate was
      22.1%. There were 458 polyps, from which 254 were adenomas. From these adenomas,
      we found an association between distal colon localization and high-grade
      dysplasia (OR 2.68 IC 1.12-6.42, p < 0.05); likewise, there was an association
      between the size of the adenomas and high-grade dysplasia (OR 7.75 IC 3.05-19.69,
      p<0.05). We did not find any association between the shape and grade of
      dysplasia. CONCLUSION: This study concludes that there is an association between
      the size of 10 mm or more and localization in the distal colon with high-grade
      dysplasia of adenomas.

PMID- 29459799
TI  - [Efficacy and safety of endoscopic resection in patients with large non
      pedunculated colorectal polyps].
AB  - INTRODUCTION: Patients with large non-pedunculated colorectal polyps (L-NPCP)
      have been traditionally treated with surgery. Advances in therapeutic endoscopy
      allow endoscopic resection of these lesions and can be considered as an
      alternative to surgery. OBJECTIVE: To evaluate the efficacy and safety of
      endoscopic resection in patients with L-NPCP. METHODS: A prospective multicentric
      cohort. All patients referred for endoscopic resection with L-NPCP between
      January 2012 and December 2015, followed until August 2016, were included. Rates
      of successful resection, recurrence and complications were obtained. Predictive
      factors associated with unsuccessful resection and recurrence were analyzed.
      RESULTS: 115 L-NPCP in 107 patients were included. The rate of successful
      resection was 92%. The most common complications were bleeding (8.7%) and
      perforation (2.6%). The recurrence rate was 7%, all successfully treated with a
      new endoscopic session. Predictors of unsuccessful resection were a measure >50
      mm of the lesion and the presence of fibrosis; and the only predictor of
      recurrence was a size of the polyp resected >50 mm. CONCLUSIONS: Endoscopic
      resection of L-NPCP is very efficacious and safe.

PMID- 29459800
TI  - [Andean megacolon and sigmoid volvulus in the high altitude. Presentation of 418
      cases between 2008 - 2012 at C. Monge Hospital, Puno, Peru].
AB  - OBJECTIVE: The present study describes the medical and surgical management of
      sigmoid volvulus due to Andean dolicomegacolon in a hospital at an altitude above
      3000 m. MATERIAL AND METHODS: A descriptive, observational, crosssectional study
      of 418 patients diagnosed with sigmoid volvulus; Admitted initially due to
      intestinal obstruction, in the Hospital of Juliaca Carlos Monge. Puno-Peru,
      during the period 2008-2012. The data were processed through the SPSS software
      version 21. RESULTS: A total of 418 patients were enrolled, the mean age was 60
      years, range 18-89 years, and the male/female ratio was 3.5/1. Nonsurgical
      management was done in 64 (15.4%), the treatment used was saline enema 20 cases
      (31%) and rectal catheter 44 (69%), recurrence was present in 27 patients (45%),
      who had surgery with primary anastomosis resection, of which the mortality
      corresponded to 8 patients (30%). Of the 354 patients undergoing emergency
      surgical management, 325 were submitted to sigmoidectomy with primary anastomosis
      (92%), while 29 had Hartmann's colostomy (8%), the morbidity for both procedures
      was 52 cases (14.7%), Mortality for both procedures was 45 cases (12.7%).
      CONCLUSIONS: In patients with sigmoid volvulus due to Andean megacolon the mean
      age was 60 years. The 15.4% had non-surgical management, the recurrence rate was
      45%, and mortality 30%. Patients with surgical management was 84.7%, from this
      group; 92% had primary anastomosis resection and 8% Hartmann colostomy, morbidity
      was 14.7% and mortality was 12.7%.

PMID- 29459801
TI  - The effect of gluten-free diet among celiac patients aged 3-12 years old on BMI
      during 2006 to 2014 at Nemazee Teaching hospital.
AB  - INTRODUCTION: Celiac disease (CD) is increasingly diagnosed and weight changes
      are common after adoption of a glutenfree diet (GFD) and there is concern that
      patients might gain further weight on a GFD. OBJECTIVES: This study examined to
      evaluate the impact of a GFD on the body mass index (BMI), whether favorable or
      unfavorable. MATERIALS AND METHODS: In this retrospective study, we reviewed
      electronic records of 44 patients with serologic study and intestinal biopsy
      confirmed CD who was visited in Nemazee hospital, Shiraz. All patients were put
      on GFD for 2 years and followed closely by pediatric gastroenterologist. BMIs
      were categories to four group underweight, normal weight, overweight and obese.
      Initial BMI and follow-up BMI was comparing together and also compared with
      general population. RESULT: At diagnosis, 27.27% of subjects were underweight,
      63.64% normal and 9.09% were obese. On a GFD, 66.66% of underweight patients
      gained weight and became normal weight and 25% of normal weight and 75% of obese
      patients had increase weight; and the rest of the patients, BMI remained stable.
      The follow-up BMIs were statistically higher than initial BMIs (mean 17.17 vs.
      15.62, p <0.0001). CONCLUSION: Individuals with celiac disease have lower BMI
      than the regional population at diagnosis. On the GFD, BMI is increased
      significantly in all categories.

PMID- 29459802
TI  - Diagnostic and therapeutic cholangioscopy in biliary diseases: a prospective
      study in Peru.
AB  - INTRODUCTION: Cholangioscopy is a test that allows the evaluation of the biliary
      epithelium. It is used for diagnosis and management of biliary diseases.
      OBJECTIVES: Determine the success rate of complete removal of difficult stones
      with the use of laser lithotripsy through cholangioscopy as well as its
      complications. Determine the visual impression accuracy of bile duct injuries.
      MATERIALS AND METHODS: This is a prospective and descriptive study. We included
      39 patients between July 2016 and July 2017 with diagnosis of difficult stones in
      the biliary tract and indeterminate stenosis of the biliary tract that were
      submitted to cholangioscopy. RESULTS: Success rate of complete removal of
      difficult stones was 65.3%, there was one complication. Two laser sessions were
      required in 4 of the 17 patients who obtained complete removal of the stones. The
      visual impression accuracy of lesions in the bile duct to determine malignancy
      coincided in all cases with the final diagnosis of the patient. CONCLUSIONS:
      Laser lithotripsy allows a safe and effective treatment of the difficult stones
      of the bile duct. Precession of visual impression of lesions in the bile duct is
      very high.

PMID- 29459803
TI  - [Prevalence and severity of the hepatopulmonar syndrome in patients with liver
      cirrhosis attended at Cayetano Heredia Hospital, between January and December
      2015].
AB  - INTRODUCTION: The hepatopulmonary syndrome (HPS) is a rare complication of liver
      cirrhosis (LC) which significantly diminishes the quality of life for people who
      suffer. OBJECTIVES: To determine the prevalence and severity of HPS in patients
      with CH treated at the Cayetano Heredia (HCH) Hospital in the period from January
      to December 2015. MATERIALS AND METHODS: Cross-sectional study with sample size
      needed to determine the point prevalence calculated in 297 patients. RESULTS: The
      prevalence of HPS in 0.7% and the identified cases were classified as mild and
      severe SHP. CONCLUSION: The prevalence of HPS is very low in the population of
      patients with liver cirrhosis treated at the Cayetano Heredia Hospital.

PMID- 29459804
TI  - [Concurrent lymphocytic colitis and microscopic enteritis in patients with
      chronic diarrhea].
AB  - INTRODUCTION: Lymphocytic colitis and microscopic enteritis are relatively common
      causes of chronic diarrhea and it is characterized by an intraepithelial
      lymphocytic infiltrate. There have been no previous reports of coexistence
      between these 2 pathologies. OBJECTIVE: To describe histological and clinical
      characteristic in patients with coexistence of lymphocytic colitis and
      microscopic enteritis. MATERIAL AND METHODS: All cases with simultaneous
      diagnosis of lymphocytic duodenosis and lymphocytic colitis were reevaluated
      during lapse time 2010-2016 in hospital Daniel Carrion. The slides were reviewed
      by 3 pathologists and clinical information was obtained from clinical records.
      Expression of CD3 and CD8 was detected in 6 cases by immunohistochemical assays.
      RESULTS: A total of 35 patients with coexistence of lymphocytic duodenitis and
      lymphocytic colitis were selected of the pathology archives, 80% were females,
      Anemia was identified in 28.5% of patients. Blastocysitis hominis infestation was
      identified in 31.8%. The mean intraepithelial lymphocyte CD8 and CD3 positive was
      40% in microscopic enteritis, while the mean intraepithelial lymphocyte CD3
      positive was 37.2% and CD8 positive was 29.2% Additionally, lymphocytic ileitis
      was diagnosed in 11 of our cases. Eosinophilic colitis was diagnosed in 9 cases
      of lymphocytic colitis Conclusion: We found that lymphocytic colitis, microscopic
      enteritis and even lymphocytic ileitis can coexist in a group of patients with
      chronic diarrhea. These findings bring the question if this concurrence of both
      pathologies constituted a more generalized gastrointestinal disorder, involving
      both the large and the small intestines.

PMID- 29459805
TI  - [Hepatitis B and C prevalence in a blood bank at general hospital in Callao,
      Peru].
AB  - OBJECTIVE: The aim of the present study was to determine the prevalence of sero
      positivity for HBsAg, Anti-HBcAg and AntiHVC in the blood bank of Hospital Daniel
      Carrion during the period 2010 - 2012. MATERIALS AND METHODS: Retrospective cross
      sectional study. Potential donors who met the inclusion criteria were included.
      Sociodemographic factors, risk behaviors were gathered. A descriptive analysis
      was performed with STATA 14. RESULTS: 13,887 potential blood donors of the HNDAC
      between January 2010 and December 2012 were identified. The population's mean was
      37 years, 32% were women. 897 potential positive blood donors were identified.
      The prevalence of HBsAg was 0.55%; Anti-HBcAg, 5.15%; and Anti-HVC, 1.25%.
      CONCLUSION: The prevalence of positive serology for HBsAg was similar to the
      previous reports and Anti-HVC was higher than the prevalence reported in our
      country.

PMID- 29459806
TI  - [Iatrogenic lesions of the biliary tract].
AB  - Iatrogenic bile duct injuries (IBDI) represent a serious surgical complication of
      laparoscopic cholecystectomy (LC). Often it occurs when the bile duct merges with
      the cystic duct; and they have been ranked by Strasberg and Bismuth, depending on
      the degree and level of injury. About third of IBDI recognized during LC, to
      detect bile leakage. No immediate repair is recommended, especially when the
      lesion is near the confluence or inflammation is associated. The drain should be
      established to control leakage of bile and prevent biliary peritonitis, before
      transferring the patient to a specialist in complex hepatobiliary surgery
      facility. In patients who are not recognized intraoperatively, the IBDI manifest
      late postoperative fever, abdominal pain, peritonitis or obstructive jaundice. If
      there is bile leak, percutaneous cholangiography should be done to define the
      biliary anatomy, and control leakage through percutaneous biliary stent. The
      repair is performed six to eight weeks after patient stabilization. If there is
      biliary obstruction, cholangiography and biliary drainage are indicated to
      control sepsis before repair. The ultimate aim is to restore the flow of bile
      into the gastrointestinal tract to prevent the formation of calculi, stenosis,
      cholangitis and biliary cirrhosis. Hepatojejunostomy with Roux-Y anastomosis
      termino-lateral without biliary stents long term, is the best choice for the
      repair of most common bile duct injury.

PMID- 29459807
TI  - [Primary biliary cholangitis. Part 1. State of the art, epidemiology,
      physiopathology and clinical manifestations].
AB  - Primary biliary cholangitis (PBC) is a chronic autoimmune cholangiopathy
      characterized by a selective destruction of biliary epithelial cells of small and
      medium caliber hepatic ducts, which mainly affects women. The main symptoms are
      fatigue and pruritus, however, a large proportion of patients may be
      asymptomatic. The diagnosis is based on AMA titers >1:40, alkaline phosphatase
      >1.5 times the upper limit for more than 24 weeks and compatible liver histology.
      It is associated with multiple autoimmune diseases mainly extrahepatic, thyroid
      diseases, bone diseases, among others. The first line treatment is
      ursodeoxycholic acid (UDCA), that improves liver function tests and delay the
      progression to cirrhosis. Currently, there are new treatments and adjuvant
      therapies on study. The purpose of this review is to offer an update in this
      topic, which is very important in gastroenterology and internal medicine. We
      formed an interdisciplinary team to search in the database Medline thorough
      PubMed with the key words describe below, we made a critical lecture of the
      titles and abstracts of each article to write this paper.

PMID- 29459808
TI  - [Submucosal endoscopic dissection in the treatment of early esophageal cancer].
AB  - We report the case of a male patient, 80 years old, with a history of dyspepsia
      and no family history of neoplasias. In the upper digestive endoscopy in the
      distal esophagus, a flat depressed lesion with the appearance of early carcinoma,
      type IIC of Paris classification, was diagnosed by biopsy as a squamous carcinoma
      in situ, infiltrating, moderately differentiated non-keratinizing grade II
      carcinoma. He underwent submucosal endoscopic dissection without complications.
      Histopathology concluded: carcinoma of squamous cells, predominantly in situ of
      distal esophagus, measuring 0.6 cm, with focus of 0.1 cm of infiltration in the
      own lamina; absence of angiolymphatic or perineural invasion. The histopathology
      specimen had margins of surgical resection free of neoplasia. Stage pT1a. Three
      months later, in the endoscopy control with biopsy of the area, there was no
      evidence of carcinoma. We present the case because it is still a challenge to
      establish the diagnosis of esophageal cancer at an early stage, especially in
      patients without symptoms, highlighting the importance of chromoendoscopy and a
      good endoscopic examination to reach the diagnosis. Submucosal endoscopy
      dissection could be considered as a safe and effective alternative treatment to
      radical surgery.

PMID- 29459809
TI  - Primary adenosquamous cell carcinoma of the pancreas: the use of endoscopic
      ultrasound guided - fine needle aspiration to establish a definitive cytologic
      diagnosis.
AB  - Pancreatic cancer is the second most common malignancy of the gastrointestinal
      tract in the US, and adenocarcinoma has been identified as the most common type
      of pancreatic cancer. Different types of pancreatic cancers have been classified:
      adenocarcinoma, ductal adenosquamous carcinoma, solid pseudopapillary tumors,
      endocrine neoplasms, acinar cell carcinoma, squamous cell carcinoma, cystic
      tumors, primary lymphoma of the pancreas, and metastatic lesions of the pancreas.
      Adenosquamous carcinoma is extremely rare, behave in a very aggressive way and is
      responsible for the 1 to 4% of the pancreatic exocrine neoplastic lesions. We
      describe the case of an 82-years-old African American female, presenting to our
      institution with quantifiable weight loss (12 kg in 3 months), jaundice and
      abdominal pain. On admission, laboratory tests were obtained: total bilirubin:
      11.07 mg/dl with a direct fraction of 10.32 mg/dl. Cross-sectional abdominal CT
      scan with contrast, showed a lesion localized in the pancreatic head (hypodense
      on T1, measuring 3.5 x 3.5 x 2.5 cm), with vascular invasion of the portal vein.
      EUS showed a solid, hypoechoic, not well-defined lesion (measuring 3.98 x 3.80
      cm), localized between the head and neck of the pancreas. EUS-FNA was performed
      with a 22G needle using the fanning technique. The cytological specimens
      demonstrated components of both squamous carcinoma and adenocarcinoma. The
      patient underwent ERCP procedure, and biliary drainage was performed with an
      entirely covered metallic stent placement. After a month from the procedures, the
      patient died due to the severity of the disease. Endoscopic ultrasound has proven
      to be the best method to diagnose solid pancreatic lesions, including rare and
      aggressive type of tumors like primary adenosquamous cell carcinoma that we
      described in this very interesting case report.

PMID- 29459810
TI  - [Pheochromocytoma giant cystic: a case report].
AB  - The giant cystic pheochromocytoma is a rare adrenal tumor in the predominantly
      asymptomatic course; so many cases are not diagnosed until the time of surgery.
      The simple mobilization of the tumor is associated with the passage to the blood
      of large amounts of catecholamines and high morbidity and mortality. So the
      surgery itself and perioperative management are a huge challenge. This article
      describes the case of a malignant giant pheochromocytoma (35 cm) which occupied
      the entire right abdomen. Even with the preoperative diagnosis of
      pheochromocytoma, pharmacological blockade preoperative and intraoperative
      measures, the patient died shortly before the end of surgery.

PMID- 29459811
TI  - [Histological complete response to neoadjuvant therapy in advanced gastric
      carcinoma. A case report and review of literature].
AB  - This communication describes the first case in the Regional Institute of
      Neoplastic Diseases "Luis Pinillos Ganoza" IREN North in which a patient with
      advanced gastric carcinoma showed complete response to neoadjuvant
      histopathologic. We describe the case of a patient woman of 70 years old with
      histopathologic diagnosis of moderately differentiated tubular gastric
      adenocarcinoma, locally advanced associated with images of perigastric
      lymphadenopathy and loss of the interface between gastric tumor, hepatic hilum
      and gallbladder. After 6 courses of neoadjuvant chemotherapy with FOLFOX scheme -
      4 to 80%, an almost complete response from the point of tomographic view is
      obtained, so the patient is underwent to distal subtotal gastrectomy
      lymphadenectomy D2 more gastrojejunoanastomosis Billroth II termino lateral type
      Hofmeister Finsterer verifying on microscopic examination of surgical specimen
      only acute and chronic gastritis with mucous areas and reactive changes. No
      feasible malignancy is observed. Lymph nodes: 0/33. Commenting on the case, a
      review of recent relevant literature is realized.

PMID- 29459812
TI  - [Gastrointestinal bleeding due to arteriovenous malformation of the jejunum].
AB  - A 23-year old male patient with no history of importance was admitted to
      Emergency because of dark red stools, tendency to lethargy and hypotension, with
      significant anemia proceeding to perform on blood transfusion, upper endoscopy,
      abdominal angiotomography and arteriography with clinical diagnosis of Dieulafoy
      lesion motivated exploratory laparotomy finding injury vascular, the jejunum with
      active bleeding. The management of severe gastrointestinal bleeding with
      hemodynamic compromise and uncommon cause of arteriovenous malformation in the
      jejunum is discussed.

PMID- 29459813
TI  - [Bronchobiliary fistula. Report of a case].
AB  - Bronchobiliary fistula (BBF) is an abnormal communication between the biliary
      tract and the bronchial tree. Is an infrequent condition, usually secondary to a
      local infectious process or a traumatic event. Bilioptisis is pathognomonic. We
      present the case of a 37 year old woman with secondary biliary cirrhosis, in list
      for liver transplantation, with several episodes of cholangitis and carrier of
      external biliary diverivation, who presented bilioptisis and HIDA scintigraphy
      with SPECT confirmed BBF. This case was resolved with percutaneous derivation of
      the biliary tract.

PMID- 29459815
TI  - Henoch-Schonlein purpura with major gastrointestinal involvement.

PMID- 29459814
TI  - [Porphyria cutanea tarda as extrahepatic manifestation of chronic hepatitis C: a
      case report].
AB  - The present case is a 56 year old male who present hyperpigmented and
      hypopigmented scars in both hands, associated with the presence of milia cysts.
      It was studied the metabolism of porphyrins and skin biopsy of the lesions which
      were compatible with porphyria cutanea tarda. In the initial laboratory, elevated
      transaminases values were found and subsequently identified chronic infection of
      hepatitis C virus. In order to treat viral infection and resolve the dermal
      commitment; considered extrahepatic manifestation of hepatitis C virus, treatment
      was started with pegylated interferon and ribavirin, with favorably development
      and rapid viral response, with undetectable viral load until now (24 weeks of
      treatment), decreased level of serum transaminases and improvement of skin
      lesions.

PMID- 29459816
TI  - Genetic Algorithm-Based Model Order Reduction of Aeroservoelastic Systems with
      Consistent States.
AB  - This paper presents a model order reduction framework to construct linear
      parameter-varying reduced-order models of flexible aircraft for
      aeroservoelasticity analysis and control synthesis in broad two-dimensional
      flight parameter space. Genetic algorithms are used to automatically determine
      physical states for reduction and to generate reduced-order models at grid points
      within parameter space while minimizing the trial-and-error process. In addition,
      balanced truncation for unstable systems is used in conjunction with the
      congruence transformation technique to achieve locally optimal realization and
      "weak" fulfillment of state consistency across the entire parameter space.
      Therefore, aeroservoelasticity reduced-order models at any flight condition can
      be obtained simply through model interpolation. The methodology is applied to the
      pitch-plant model of the X-56A Multi-Use Technology Testbed currently being
      tested at NASA Armstrong Flight Research Center for flutter suppression and gust
      load alleviation. The present studies indicate that the reduced-order model with
      more than 12* reduction in the number of states relative to the original model is
      able to accurately predict system response among all input-output channels. The
      genetic-algorithm-guided approach exceeds manual and empirical state selection in
      terms of efficiency and accuracy. The interpolated aeroservoelasticity reduced
      order models exhibit smooth pole transition and continuously varying gains along
      a set of prescribed flight conditions, which verifies consistent state
      representation obtained by congruence transformation. The present model order
      reduction framework can be used by control engineers for robust
      aeroservoelasticity controller synthesis and novel vehicle design.

PMID- 29459817
TI  - Altered Expression of Matrix Metalloproteinases and Their Endogenous Inhibitors
      in a Human Isogenic Stem Cell Model of Huntington's Disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      characterized by a progressive movement disorder, psychiatric symptoms, and
      cognitive impairments. HD is caused by a CAG repeat expansion encoding a stretch
      of polyglutamine residues in the N-terminus of mutant huntingtin (mHTT) protein.
      Proteolytic processing of mHTT yields toxic fragments, which cause neurotoxicity
      and massive neuronal cell death predominantly in the striatum and cortex.
      Inhibition of mHTT cleavage reduces neuronal toxicity suggesting mHTT proteolysis
      contributes to HD pathogenesis. A previously conducted unbiased siRNA screen in
      our lab for known human proteases identified matrix metalloproteinases (MMPs) as
      modifiers of mHTT proteolysis and toxicity. To further study MMP activation in
      HD, isogenic HD, and control corrected (C116) neural stem cells (NSCs) prepared
      from HD patient-derived induced pluripotent stem cells were used to examine the
      role of MMPs and their endogenous inhibitors in this highly relevant model
      system. We found altered expression of MMP-2 and MMP-9 (gelatinases), MMP-3/10,
      and MMP-14, activity in HD-NSCs when compared to control C116-NSCs. Dysregulation
      in MMP activity was accompanied with concomitant changes in levels of endogenous
      inhibitors of MMPs, called tissue inhibitors of matrix metalloproteinases
      (TIMPs). Specifically, we observed decreased levels of TIMP-1 and TIMP-2 in HD
      NSCs, suggesting part of the altered expression and activity of MMPs is due to
      lower abundance of these endogenous inhibitors. Immunofluorescence analysis
      revealed increased MMP/TIMP localization in the nucleus or aggregates of HD-NSCs,
      suggesting potential interaction with mHTT. TIMP-1 was found to associate with
      mHTT aggregates in discrete punctate structures in HD-NSCs. These events
      collectively contribute to increased neurotoxicity in HD. Previous
      characterization of these NSCs revealed transforming growth factor beta (TGF
      beta) pathway as the top dysregulated pathway in HD. TGF-beta was significantly
      upregulated in HD-NSCs and addition of TGF-beta to HD-NSCs was found to be
      neuroprotective. To determine if TGF-beta regulated MMP and TIMP activity, C116-
      and HD-NSCs were exogenously treated with recombinant TGF-beta. TIMP-1 levels
      were found to be elevated in response to TGF-beta treatment, representing a
      potential mechanism through which elevated TGF-beta levels confer neuroprotection
      in HD. Studying the mechanism of action of MMPs and TIMPs, and their interactions
      with mHTT in human isogenic patient-derived NSCs elucidates new mechanisms of HD
      neurotoxicity and will likely provide novel therapeutics for treatment of HD.

PMID- 29459818
TI  - Gestational Exposure to the Synthetic Cathinone Methylenedioxypyrovalerone
      Results in Reduced Maternal Care and Behavioral Alterations in Mouse Pups.
AB  - The member of synthetic cathinone family, methylenedioxypyrovalerone (MDPV), is a
      frequently used psychoactive drug of abuse. The objective of our study was to
      determine the effect of MDPV (administered from the 8th to the 14th day of
      gestation) on the behavior of neonatal and adolescent mice, as well as its effect
      on maternal care. We measured maternal care (pup retrieval test, nest building),
      locomotor activity (open field test), and motor coordination (grip strength test)
      of dams, whereas on pups we examined locomotor activity at postnatal day 7 and
      day 21 (open field test) and motor coordination on day 21 (grip strength test).
      On fresh-frozen brain samples of the dams we examined the expression of two
      important peptides implicated in the regulation of maternal behavior and
      lactation: tuberoinfundibular peptide 39 (TIP39) mRNA in the thalamic posterior
      intralaminar complex, and amylin mRNA in the medial preoptic nucleus. We detected
      decreased birth rate and survival of offspring, and reduced maternal care in the
      drug-treated animals, whereas there was no difference between the motility of
      treated and control mothers. Locomotor activity of the pups was increased in the
      MDPV treated group both at 7 and 21 days of age, while motor coordination was
      unaffected by MDPV treatment. TIP39 and amylin were detected in their typical
      location but failed to show a significant difference of expression between the
      drug-treated and control groups. The results suggest that chronic systemic
      administration of the cathinone agent MDPV to pregnant mice can reduce birth rate
      and maternal care, and it also enhances motility (without impairment of motor
      coordination) of the offspring.

PMID- 29459819
TI  - Ganglioside Metabolism and Parkinson's Disease.
AB  - Here we advance the hypothesis that Parkinson's disease (PD) is fundamentally a
      failure of trophic support for specific classes of neurons, primarily
      catecholaminergic. Evidence from our laboratory provides a framework into which a
      broad array of findings from many quarters can be integrated into a general
      theory that offers testable hypotheses to new and established investigators. Mice
      deficient in the ability to synthesize series-a gangliosides, specifically GM1
      ganglioside, develop parkinsonism. We found that this seems to be due to a
      failure in signaling efficiency by the important catecholaminergic growth factor,
      GDNF. Interestingly, these mice accumulate alpha-synuclein in nigral neurons.
      Striatal over-expression of GDNF eliminates these aggregates and also restores
      normal motor function. These findings bring into question common beliefs about
      alpha-synuclein pathology and may help us to reinterpret other experimental
      findings in a new light. The purpose of this article is to provoke new thinking
      about PD and hopefully encourage younger scientists to explore some of the ideas
      presented below.

PMID- 29459820
TI  - High Throughput Measurement of Locomotor Sensitization to Volatilized Cocaine in
      Drosophila melanogaster.
AB  - Drosophila melanogaster can be used to identify genes with novel functional roles
      in neuronal plasticity induced by repeated consumption of addictive drugs.
      Behavioral sensitization is a relatively simple behavioral output of plastic
      changes that occur in the brain after repeated exposures to drugs of abuse. The
      development of screening procedures for genes that control behavioral
      sensitization has stalled due to a lack of high-throughput behavioral tests that
      can be used in genetically tractable organism, such as Drosophila. We have
      developed a new behavioral test, FlyBong, which combines delivery of volatilized
      cocaine (vCOC) to individually housed flies with objective quantification of
      their locomotor activity. There are two main advantages of FlyBong: it is high
      throughput and it allows for comparisons of locomotor activity of individual
      flies before and after single or multiple exposures. At the population level,
      exposure to vCOC leads to transient and concentration-dependent increase in
      locomotor activity, representing sensitivity to an acute dose. A second exposure
      leads to further increase in locomotion, representing locomotor sensitization. We
      validate FlyBong by showing that locomotor sensitization at either the population
      or individual level is absent in the mutants for circadian genes period (per),
      Clock (Clk), and cycle (cyc). The locomotor sensitization that is present in
      timeless (tim) and pigment dispersing factor (pdf) mutant flies is in large part
      not cocaine specific, but derived from increased sensitivity to warm air.
      Circadian genes are not only integral part of the neural mechanism that is
      required for development of locomotor sensitization, but in addition, they
      modulate the intensity of locomotor sensitization as a function of the time of
      day. Motor-activating effects of cocaine are sexually dimorphic and require a
      functional dopaminergic transporter. FlyBong is a new and improved method for
      inducing and measuring locomotor sensitization to cocaine in individual
      Drosophila. Because of its high-throughput nature, FlyBong can be used in genetic
      screens or in selection experiments aimed at the unbiased identification of
      functional genes involved in acute or chronic effects of volatilized psychoactive
      substances.

PMID- 29459821
TI  - Pre- and Postsynaptic Activation of GABAB Receptors Modulates Principal Cell
      Excitation in the Piriform Cortex.
AB  - The piriform cortex (PC), like other cortical regions, normally operates in a
      state of dynamic equilibrium between excitation and inhibition. Here we examined
      the roles played by pre- and postsynaptic GABAB receptors in maintaining this
      equilibrium in the PC. Using whole-cell recordings in brain slices from the
      anterior PC of mice, we found that synaptic activation of postsynaptic GABAB
      receptors hyperpolarized the two major classes of layer 2 principal neurons and
      reduced the intrinsic electrical excitability of these neurons. Presynaptic GABAB
      receptors are expressed on the terminals of associational (intracortical)
      glutamatergic axons in the PC. Heterosynaptic activation of these receptors
      reduced excitatory associational inputs onto principal cells. Presynaptic GABAB
      receptors are also expressed on the axons of GABAergic interneurons in the PC,
      and blockade of these autoreceptors enhanced inhibitory inputs onto principal
      cells. Hence, presynaptic GABAB autoreceptors produce disinhibition of principal
      cells. To study the functional consequences of GABAB activation in vivo, we used
      2-photon calcium imaging to simultaneously monitor the activity of ~200 layer 2
      neurons. Superfusion of the GABAB agonist baclofen reduced spontaneous random
      firing but also promoted synchronous epileptiform activity. These findings
      suggest that, while GABAB activation can dampen excitability by engaging pre- and
      postsynaptic GABAB heteroreceptors on glutamatergic neurons, it can also promote
      excitability by disinhibiting principal cells by activating presynaptic GABAB
      autoreceptors on interneurons. Thus, depending on the dynamic balance of hetero-
      and autoinhibition, GABAB receptors can function as variable modulators of
      circuit excitability in the PC.

PMID- 29459822
TI  - Neuromodulation via the Cerebrospinal Fluid: Insights from Recent in Vitro
      Studies.
AB  - The cerebrospinal fluid (CSF) occupies the brain's ventricles and subarachnoid
      space and, together with the interstitial fluid (ISF), forms a continuous fluidic
      network that bathes all cells of the central nervous system (CNS). As such, the
      CSF is well positioned to actively distribute neuromodulators to neural circuits
      in vivo via volume transmission. Recent in vitro experimental work in brain
      slices and neuronal cultures has shown that human CSF indeed contains
      neuromodulators that strongly influence neuronal activity. Here we briefly
      summarize these new findings and discuss their potential relevance to neural
      circuits in health and disease.

PMID- 29459823
TI  - Effects of Social Experience on the Habituation Rate of Zebrafish Startle Escape
      Response: Empirical and Computational Analyses.
AB  - While the effects of social experience on nervous system function have been
      extensively investigated in both vertebrate and invertebrate systems, our
      understanding of how social status differentially affects learning remains
      limited. In the context of habituation, a well-characterized form of non
      associative learning, we investigated how the learning processes differ between
      socially dominant and subordinate in zebrafish (Danio rerio). We found that
      social status and frequency of stimulus inputs influence the habituation rate of
      short latency C-start escape response that is initiated by the Mauthner neuron (M
      cell). Socially dominant animals exhibited higher habituation rates compared to
      socially subordinate animals at a moderate stimulus frequency, but low stimulus
      frequency eliminated this difference of habituation rates between the two social
      phenotypes. Moreover, habituation rates of both dominants and subordinates were
      higher at a moderate stimulus frequency compared to those at a low stimulus
      frequency. We investigated a potential mechanism underlying these status
      dependent differences by constructing a simplified neurocomputational model of
      the M-cell escape circuit. The computational study showed that the change in
      total net excitability of the model M-cell was able to replicate the experimental
      results. At moderate stimulus frequency, the model M-cell with lower total net
      excitability, that mimicked a dominant-like phenotype, exhibited higher
      habituation rates. On the other hand, the model with higher total net
      excitability, that mimicked the subordinate-like phenotype, exhibited lower
      habituation rates. The relationship between habituation rates and characteristics
      (frequency and amplitude) of the repeated stimulus were also investigated. We
      found that habituation rates are decreasing functions of amplitude and increasing
      functions of frequency while these rates depend on social status (higher for
      dominants and lower for subordinates). Our results show that social status
      affects habituative learning in zebrafish, which could be mediated by a summative
      neuromodulatory input to the M-cell escape circuit, which enables animals to
      readily learn to adapt to changes in their social environment.

PMID- 29459824
TI  - EGR3 Immediate Early Gene and the Brain-Derived Neurotrophic Factor in Bipolar
      Disorder.
AB  - Bipolar disorder (BD) is a severe psychiatric illness with a consistent genetic
      influence, involving complex interactions between numerous genes and
      environmental factors. Immediate early genes (IEGs) are activated in the brain in
      response to environmental stimuli, such as stress. The potential to translate
      environmental stimuli into long-term changes in brain has led to increased
      interest in a potential role for these genes influencing risk for psychiatric
      disorders. Our recent finding using network-based approach has shown that the
      regulatory unit of early growth response gene 3 (EGR3) of IEGs family was
      robustly repressed in postmortem prefrontal cortex of BD patients. As a central
      transcription factor, EGR3 regulates an array of target genes that mediate
      critical neurobiological processes such as synaptic plasticity, memory and
      cognition. Considering that EGR3 expression is induced by brain-derived
      neurotrophic factor (BDNF) that has been consistently related to BD
      pathophysiology, we suggest a link between BDNF and EGR3 and their potential role
      in BD. A growing body of data from our group and others has shown that peripheral
      BDNF levels are reduced during mood episodes and also with illness progression.
      In this same vein, BDNF has been proposed as an important growth factor in the
      impaired cellular resilience related to BD. Taken together with the fact that
      EGR3 regulates the expression of the neurotrophin receptor p75NTR and may also
      indirectly induce BDNF expression, here we propose a feed-forward gene regulatory
      network involving EGR3 and BDNF and its potential role in BD.

PMID- 29459825
TI  - Aging Potentiates Lateral but Not Local Inhibition of Orientation Processing in
      Primary Visual Cortex.
AB  - Aging-related declines in vision can decrease well-being of the elderly.
      Concerning early sensory changes as in the primary visual cortex, physiological
      and behavioral reports seem contradictory. Neurophysiological studies on
      orientation tuning properties suggested that neuronal changes might come from
      decreased cortical local inhibition. However, behavioral results either showed no
      clear deficits in orientation processing in older adults, or proposed stronger
      surround suppression. Through psychophysical experiments and computational
      modeling, we resolved these discrepancies by suggesting that lateral inhibition
      increased in older adults while neuronal orientation tuning widths, related to
      local inhibition, stayed globally intact across age. We confirmed this later
      result by re-analyzing published neurophysiological data, which showed no
      systematic tuning width changes, but instead displayed a higher neuronal noise
      with aging. These results suggest a stronger lateral inhibition and mixed effects
      on local inhibition during aging, revealing a more complex picture of age-related
      effects in the central visual system than people previously thought.

PMID- 29459826
TI  - Age Effects in Postural Control Analyzed via a Principal Component Analysis of
      Kinematic Data and Interpreted in Relation to Predictions of the Optimal Feedback
      Control Theory.
AB  - Optimal feedback control theory suggests that control of movement is focused on
      movement dimensions that are important for the task's success. The current study
      tested the hypotheses that age effects would emerge in the control of only
      specific movement components and that these components would be linked to the
      task relevance. Fifty healthy volunteers, 25 young and 25 older adults, performed
      a 80s-tandem stance while their postural movements were recorded using a standard
      motion capture system. The postural movements were decomposed by a principal
      component analysis into one-dimensional movement components, PMk, whose control
      was assessed through two variables, Nk and sigmak, which characterized the
      tightness and the regularity of the neuro-muscular control, respectively. The
      older volunteers showed less tight and more irregular control in PM2 (N2: -9.2%,
      p = 0.007; sigma2: +14.3.0%, p = 0.017) but tighter control in PM8 and PM9 (N8:
      +4.7%, p = 0.020; N9: +2.5%, p = 0.043; sigma9: -8.8%, p = 0.025). These results
      suggest that aging effects alter the postural control system not as a whole, but
      emerge in specific, task relevant components. The findings of the current study
      thus support the hypothesis that the minimal intervention principle, as described
      in the context of optimal feedback control (OFC), may be relevant when assessing
      aging effects on postural control.

PMID- 29459827
TI  - Rosmarinic Acid Activates AMPK to Inhibit Metastasis of Colorectal Cancer.
AB  - Rosmarinic acid (RA) has been used as an anti-inflammatory, anti-diabetic, and
      anti-cancer agent. Although RA has also been shown to exert an anti-metastatic
      effect, the mechanism of this effect has not been reported to be associated with
      AMP-activated protein kinase (AMPK). The aim of this study was to elucidate
      whether RA could inhibit the metastatic properties of colorectal cancer (CRC)
      cells via the phosphorylation of AMPK. RA inhibited the proliferation of CRC
      cells through the induction of cell cycle arrest and apoptosis. In several
      metastatic phenotypes of CRC cells, RA regulated epithelial-mesenchymal
      transition (EMT) through the upregulation of an epithelial marker, E-cadherin,
      and the downregulation of the mesenchymal markers, N-cadherin, snail, twist,
      vimentin, and slug. Invasion and migration of CRC cells were inhibited and
      expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were decreased by RA
      treatment. Adhesion and adhesion molecules such as ICAM-1 and integrin beta1
      expressions were also reduced by RA treatment. In particular, the effects of RA
      on EMT and MMPs expressions were due to the activation of AMPK. Moreover, RA
      inhibited lung metastasis of CRC cells by activating AMPK in mouse model.
      Collectively, these results proved that RA could be potential therapeutic agent
      against metastasis of CRC.

PMID- 29459828
TI  - Nature-Based Tourism Elicits a Phenotypic Shift in the Coping Abilities of Fish.
AB  - Nature-based tourism is gaining extensive popularity, increasing the intensity
      and frequency of human-wildlife contacts. As a consequence, behavioral and
      physiological alterations were observed in most exposed animals. However, while
      the majority of these studies investigated the effects of punctual exposure to
      tourists, the consequences of constant exposition to humans in the wild remains
      overlooked. This is an important gap considering the exponential interest for
      recreational outdoor activities. To infer long-term effects of intensive tourism,
      we capitalized on Odontostilbe pequira, a short-lived sedentary Tetra fish who
      spends its life close to humans, on which it feeds on dead skin. Hence, those
      fish are constantly exposed to tourists throughout their lifecycle. Here we
      provide an integrated picture of the whole phenomenon by investigating, for the
      first time, the expression of genes involved in stress response and neurogenesis,
      as well as behavioral and hormonal responses of animals consistently exposed to
      tourists. Gene expression of the mineralocorticoid (and cortisol) receptor (mr)
      and the neurogenic differentiation factor (NeuroD) were significantly higher in
      fish sampled in the touristic zone compared to those sampled in the control zone.
      Additionally, after a simulated stress in artificial and controlled conditions,
      those fish previously exposed to visitors produced more cortisol and presented
      increased behavioral signs of stress compared to their non-exposed conspecifics.
      Overall, nature-based tourism appeared to shift selection pressures, favoring a
      sensitive phenotype that does not thrive under natural conditions. The ecological
      implications of this change in coping style remain, nevertheless, an open
      question.

PMID- 29459829
TI  - Stimulation of JNK Phosphorylation by the PTTH in Prothoracic Glands of the
      Silkworm, Bombyx mori.
AB  - In this study, phosphorylation of c-Jun N-terminal kinase (JNK) by the
      prothoracicotropic hormone (PTTH) was investigated in prothoracic glands (PGs) of
      the silkworm, Bombyx mori. Results showed that JNK phosphorylation was stimulated
      by the PTTH in time- and dose-dependent manners. In vitro activation of JNK
      phosphorylation in PGs by the PTTH was also confirmed in an in vivo experiment,
      in which a PTTH injection greatly increased JNK phosphorylation in PGs of day-6
      last instar larvae. JNK phosphorylation caused by PTTH stimulation was greatly
      inhibited by U73122, a potent and specific inhibitor of phospholipase C (PLC) and
      an increase in JNK phosphorylation was also detected when PGs were treated with
      agents (either A23187 or thapsigargin) that directly elevated the intracellular
      Ca2+ concentration, thereby indicating involvement of PLC and Ca2+. Pretreatment
      with an inhibitor (U0126) of mitogen-activated protein kinase
      (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) and an inhibitor
      (LY294002) of phosphoinositide 3-kinase (PI3K) failed to significantly inhibit
      PTTH-stimulated JNK phosphorylation, indicating that ERK and PI3K were not
      related to JNK. We further investigated the effect of modulation of the redox
      state on JNK phosphorylation. In the presence of either an antioxidant (N
      acetylcysteine, NAC) or diphenylene iodonium (DPI), PTTH-stimulated JNK
      phosphorylation was blocked. The JNK kinase inhibitor, SP600125, markedly
      inhibited PTTH-stimulated JNK phosphorylation and ecdysteroid synthesis. The
      kinase assay of JNK in PGs confirmed its stimulation by PTTH and inhibition by
      SP600125. Moreover, PTTH treatment did not affect JNK or Jun mRNA expressions.
      Based on these findings, we concluded that PTTH stimulates JNK phosphorylation in
      Ca2+- and PLC-dependent manners and that the redox-regulated JNK signaling
      pathway is involved in PTTH-stimulated ecdysteroid synthesis in B. mori PGs.

PMID- 29459831
TI  - Relative Handgrip Strength Is Inversely Associated with Metabolic Profile and
      Metabolic Disease in the General Population in China.
AB  - Background: Absolute handgrip strength has been correlated with metabolic profile
      and metabolic disease. Whether relative handgrip strength is also associated with
      metabolic disease has not been assessed. This study aimed at assessing the
      association of relative handgrip strength with metabolic profile and metabolic
      disease in the general population in China. Methods: Data were derived from an
      ongoing cross-sectional survey of the 2013 National Physical and Health in Shanxi
      Province, which involved 5520 participants. Multiple linear regression or
      multiple logistic regression analysis were used to assess the association of
      absolute/relative handgrip strength with the metabolic profile, preclinical, and
      established stages of metabolic diseases. Results: This study revealed that
      relative handgrip strength, that is when normalized to BMI, was associated with:
      (1) in both genders for more favorable blood lipid levels of high-density
      lipoprotein cholesterol [males: b = 0.19 (0.15, 0.23); females: b = 0.22 (0.17,
      0.28)], low-density lipoprotein cholesterol [males: b = -0.14 (-0.23, -0.05);
      females: b = -0.19 (-0.31, -0.18)], triglycerides [males: b = -0.58 (-0.74, 
      0.43); females: b = -0.55 (-0.74, -0.36)] and total cholesterol [males: b = -0.20
      (-0.31, -0.10); females: b = -0.19 (-0.32, -0.06)]; and better serum glucose
      levels in males [b = -0.30 (-0.46, -0.15)]. (2) lower risk of impaired fasting
      glucose in males {third quartile [OR = 0.66 (0.45-0.95)] and fourth quartile [OR
      = 0.46 (0.30-0.71)] vs. first quartile} and dyslipidemia in both genders {third
      quartile [males: OR = 0.65 (0.48-0.87); females: OR = 0.68 (0.53-0.86)] and
      fourth quartile [males: OR = 0.47 (0.35-0.64); females: OR = 0.47(0.36-0.61)] vs.
      first quartile}. (3) lower risk of hyperlipidemia in both genders third quartile
      [males: OR = 0.66 (0.50-0.87); females: OR = 0.57 (0.43-0.75)] and fourth
      quartile [males: OR = 0.35 (0.26-0.47); females: OR = 0.51 (0.38-0.70)] vs. first
      quartile. However, contrary to relative handgrip strength, higher absolute
      handgrip strength was associated with unfavorable metabolic profiles and higher
      risk of metabolic diseases. These paradoxical associations were retained even
      after adjusted for BMI by employed a multivariate analysis. Conclusion: We
      conclude that measurement of relative handgrip strength can be used as a
      reasonable clinical predictor of metabolic health and disease.

PMID- 29459830
TI  - Coenzyme Q10 Supplementation in Aging and Disease.
AB  - Coenzyme Q (CoQ) is an essential component of the mitochondrial electron
      transport chain and an antioxidant in plasma membranes and lipoproteins. It is
      endogenously produced in all cells by a highly regulated pathway that involves a
      mitochondrial multiprotein complex. Defects in either the structural and/or
      regulatory components of CoQ complex or in non-CoQ biosynthetic mitochondrial
      proteins can result in a decrease in CoQ concentration and/or an increase in
      oxidative stress. Besides CoQ10 deficiency syndrome and aging, there are chronic
      diseases in which lower levels of CoQ10 are detected in tissues and organs
      providing the hypothesis that CoQ10 supplementation could alleviate aging
      symptoms and/or retard the onset of these diseases. Here, we review the current
      knowledge of CoQ10 biosynthesis and primary CoQ10 deficiency syndrome, and have
      collected published results from clinical trials based on CoQ10 supplementation.
      There is evidence that supplementation positively affects mitochondrial
      deficiency syndrome and the symptoms of aging based mainly on improvements in
      bioenergetics. Cardiovascular disease and inflammation are alleviated by the
      antioxidant effect of CoQ10. There is a need for further studies and clinical
      trials involving a greater number of participants undergoing longer treatments in
      order to assess the benefits of CoQ10 treatment in metabolic syndrome and
      diabetes, neurodegenerative disorders, kidney diseases, and human fertility.

PMID- 29459832
TI  - Variations of the Functional Brain Network Efficiency in a Young Clinical Sample
      within the Autism Spectrum: A fNIRS Investigation.
AB  - Autism is a neurodevelopmental disorder with dimensional behavioral symptoms and
      various damages in the structural and functional brain. Previous neuroimaging
      studies focused on exploring the differences of brain development between
      individuals with and without autism spectrum disorders (ASD). However, few of
      them have attempted to investigate the individual differences of the brain
      features among subjects within the Autism spectrum. Our main goal was to explore
      the individual differences of neurodevelopment in young children with Autism by
      testing for the association between the functional network efficiency and levels
      of autistic behaviors, as well as the association between the functional network
      efficiency and age. Forty-six children with Autism (ages 2.0-8.9 years old)
      participated in the current study, with levels of autistic behaviors evaluated by
      their parents. The network efficiency (global and local network efficiency) were
      obtained from the functional networks based on the oxy-, deoxy-, and total
      Hemoglobin series, respectively. Results indicated that the network efficiency
      decreased with age in young children with Autism in the deoxy- and total
      Hemoglobin-based-networks, and children with a relatively higher level of
      autistic behaviors showed decreased network efficiency in the oxy-hemoglobin
      based network. Results suggest individual differences of brain development in
      young children within the Autism spectrum, providing new insights into the
      psychopathology of ASD.

PMID- 29459834
TI  - Suicidal Risk, Psychopathology, and Quality of Life in a Clinical Population of
      Adolescents.
AB  - Background: According to literature data, psychopathology is associated with both
      quality of life (QoL) and suicidal risk in adolescents, but the literature does
      not fully support a direct association between psychopathology and suicidal
      thoughts and behaviors. The aim of this study was to investigate the possible
      mediational role of QoL in the relationship between psychopathology and level of
      suicidal risk in a clinical sample of adolescents. Method: The authors examined a
      clinical population of 134 adolescents, aged 13-18 years. Suicidal risk-having
      any current suicidal ideations and/or previous suicide attempt-was assessed by
      the Mini International Neuropsychiatric Interview. QoL was evaluated by the
      adolescent self-rated versions of "Das Intervertar zur Erfassung der
      Lebensqualitat Kindern und Jugendlichen" (ILK: Measure of Quality of Life for
      Children and Adolescents) and psychopathology was measured by adolescent self
      rated versions of the Strengths and Difficulties Questionnaire (SDQ). A
      mediational model, in which QoL mediated the relationship between psychopathology
      and suicidal risk controlling for gender and age, was tested by means of
      regression analyses. Results: Gender and age were both associated with suicidal
      risk. Self-reported QoL significantly mediated the relationships between
      emotional problems (=1.846; 95% BCa CI: 0.731-2.577), as well as peer problems
      (=0.883; 95% BCa CI: 0.055-1.561) and suicidal risk: more emotional and peer
      problems were associated with lower QoL, which in turn was related to higher
      level of suicidal risk. Conclusion: Based on this study, which aims to make
      further steps in suicidal prevention, our findings suggest that clinicians should
      routinely screen the QoL of their patients, especially in adolescents with
      emotional and peer problems. Furthermore, it is important to focus intervention
      and treatment efforts on improving the QoL of adolescents with emotional and peer
      problems.

PMID- 29459833
TI  - Potential and Challenges for the Clinical Use of d-Serine As a Cognitive
      Enhancer.
AB  - After 25 years of its discovery in the rat brain, d-serine is a recognized
      modulator of synaptic plasticity and cognitive processes through its actions on
      the NMDA-glutamate receptor. Importantly, cognitive impairment is a core feature
      of conditions, such as schizophrenia, Alzheimer's disease, depression, and aging,
      and is associated to disturbances in NMDA-glutamate receptors. The d-serine
      pathway has been associated with cognitive deficits and these conditions, and,
      for this reason, d-serine signaling is subject of intense research to probe its
      role in aiding diagnosis and therapy. Nevertheless, this has not resulted in new
      therapies being incorporated into clinical practice. Therefore, in this review we
      will address many questions that need to be solved by future studies, regarding d
      serine pharmacokinetics, possible side effects, other strategies to modulate its
      levels, and combination with other therapies to increase its efficacy.

PMID- 29459835
TI  - Asymmetric Drug-Induced Parkinsonism and Psychopathology: A Prospective
      Naturalistic Study in Long-Stay Psychiatric Patients.
AB  - Background: Drug-induced parkinsonism (DIP) is the most common movement disorder
      induced by antipsychotics. Although DIP is mostly symmetric, asymmetric DIP is
      reported in a substantial part of the patients. We investigated the frequency of
      motor asymmetry in DIP and its relationship to the severity of psychopathology in
      long-stay psychiatric patients. Methods: We obtained data from a cohort study of
      207 long-stay psychiatric patients on the frequency and risk factors of tardive
      dyskinesia, akathisia, tardive dystonia, and DIP. From July 2003 to May 2007
      (mean follow-up, 1.1 year) drug-induced movement disorders were assessed at least
      two times in each patient, with a frequency of persistent DIP of 56.2%. All
      patients who had at least one time parkinsonism in the upper/lower limb(s) were
      included for analyses (190 patients, 79 women; mean age, 48.0 +/- 12.9 years).
      The Unified Parkinson Disease Rating Scale motor scale was used to calculate the
      frequency of asymmetric parkinsonism. Multilevel mixed models were built to
      explore the relationship between asymmetry in parkinsonism and the severity of
      psychopathology, measured on the Clinical Global Impression-Schizophrenia scale
      severity index (CGI-SCH SI). Results: The frequency of asymmetric parkinsonism
      was 20.8%. Asymmetry in parkinsonism was associated with symptom severity on all
      CGI-SCH SI scales (beta range, 0.37-3.74) and significantly associated with the
      positive symptom scale (beta, 3.74; 95% CI, 0.35-7.31). Conclusion: DIP is
      asymmetric in a substantial part of patients. Asymmetric presentation of DIP is
      of clinical relevance as it is related to the severity of psychopathology and may
      alert the clinician of more severe psychopathology. Future research is
      recommended to provide insight into the neuropsychopathology and clinical value
      of asymmetric parkinsonism for psychiatric patients.

PMID- 29459837
TI  - Effects of Relaxing and Arousing Music during Imagery Training on Dart-Throwing
      Performance, Physiological Arousal Indices, and Competitive State Anxiety.
AB  - Music that is carefully selected to match the requirements of activities and the
      characteristics of individuals has been shown to produce significant impacts on
      performance enhancement (Priest et al., 2004). There is also evidence that music
      can enhance imagery (Grocke and Wigram, 2007), although few studies have
      investigated the effects of music on imagery in the context of sport skills. In
      the present study, the effects of relaxing and arousing music during imagery on
      dart-throwing performance, physiological arousal indices, and competitive state
      anxiety, were investigated among 63 novice dart throwers. Participants had
      moderate-to-high imagery ability and were randomly assigned to unfamiliar
      relaxing music (URM), unfamiliar arousing music (UAM), or no music (NM) groups.
      Performance was assessed by 40 dart throws at a concentric circles dartboard
      before and after 12 imagery sessions over 4 weeks. Measures of galvanic skin
      response (GSR), peripheral temperature (PT), and heart rate (HR) were taken
      during imagery sessions 1 and 12, and the Competitive State Anxiety Inventory-2
      Revised (CSAI-2R) was administered prior to the pre- and post-intervention
      performance task. Dart-throwing gain scores were significantly higher for URM
      than for UAM and NM, with no significant difference between UAM and NM (URM =
      37.24 +/- 5.66, UAM = 17.57 +/- 5.30, and NM = 13.19 +/- 6.14, F2,62 = 5.03, p =
      0.01, eta2 = 0.14). GSR, PT, and HR reflected lower arousal for URM than for UAM
      or NM. Significant decreases in somatic anxiety were evident for URM and UAM but
      not NM. Significant decreases in cognitive anxiety were evident for URM and NM
      but not UAM. Significant increases in self-confidence were evident for URM but
      not UAM or NM. Performance improved in all three conditions but URM was
      associated with the largest performance gain, the lowest physiological indices of
      arousal, and the most positive CSAI-2R profiles. Listening to relaxing music
      during imagery may have benefits for performance in other fine motor skills.

PMID- 29459838
TI  - Characterizing and Measuring Maliciousness for Cybersecurity Risk Assessment.
AB  - Cyber attacks have been increasingly detrimental to networks, systems, and users,
      and are increasing in number and severity globally. To better predict system
      vulnerabilities, cybersecurity researchers are developing new and more holistic
      approaches to characterizing cybersecurity system risk. The process must include
      characterizing the human factors that contribute to cyber security
      vulnerabilities and risk. Rationality, expertise, and maliciousness are key human
      characteristics influencing cyber risk within this context, yet maliciousness is
      poorly characterized in the literature. There is a clear absence of literature
      pertaining to human factor maliciousness as it relates to cybersecurity and only
      limited literature relating to aspects of maliciousness in other disciplinary
      literatures, such as psychology, sociology, and law. In an attempt to
      characterize human factors as a contribution to cybersecurity risk, the
      Cybersecurity Collaborative Research Alliance (CSec-CRA) has developed a Human
      Factors risk framework. This framework identifies the characteristics of an
      attacker, user, or defender, all of whom may be adding to or mitigating against
      cyber risk. The maliciousness literature and the proposed maliciousness
      assessment metrics are discussed within the context of the Human Factors
      Framework and Ontology. Maliciousness is defined as the intent to harm. Most
      maliciousness cyber research to date has focused on detecting malicious software
      but fails to analyze an individual's intent to do harm to others by deploying
      malware or performing malicious attacks. Recent efforts to identify malicious
      human behavior as it relates to cybersecurity, include analyzing motives driving
      insider threats as well as user profiling analyses. However, cyber-related
      maliciousness is neither well-studied nor is it well understood because
      individuals are not forced to expose their true selves to others while performing
      malicious attacks. Given the difficulty of interviewing malicious-behaving
      individuals and the potential untrustworthy nature of their responses, we aim to
      explore the maliciousness as a human factor through the observable behaviors and
      attributes of an individual from their actions and interactions with society and
      networks, but to do so we will need to develop a set of analyzable metrics. The
      purpose of this paper is twofold: (1) to review human maliciousness-related
      literature in diverse disciplines (sociology, economics, law, psychology,
      philosophy, informatics, terrorism, and cybersecurity); and (2) to identify an
      initial set of proposed assessment metrics and instruments that might be culled
      from in a future effort to characterize human maliciousness within the cyber
      realm. The future goal is to integrate these assessment metrics into holistic
      cybersecurity risk analyses to determine the risk an individual poses to
      themselves as well as other networks, systems, and/or users.

PMID- 29459836
TI  - Treating Depression with Transcutaneous Auricular Vagus Nerve Stimulation: State
      of the Art and Future Perspectives.
AB  - Depression is a highly prevalent disorder, and its treatment is far from
      satisfactory. There is an urgent need to develop a new treatment for depression.
      Although still at its early stage, transcutaneous auricular vagus nerve
      stimulation (taVNS) has shown promising potential for treating depression. In
      this article, we first summarize the results of clinical studies on the treatment
      effect of taVNS on depression. Then, we re-analyze a previous study to identify
      the specific symptoms taVNS can relieve as indicated by subscores of the 24-item
      Hamilton Depression Scale in patients with depression. We found that taVNS can
      significantly reduce multiple symptoms of depression patients, including anxiety,
      psychomotor retardation, sleep disturbance, and hopelessness. Next, we pose
      several hypotheses on the mechanism of taVNS treatment of depression, including
      directly and indirectly modulating the activity and connectivity of key brain
      regions involved in depression and mood regulation; inhibiting neuro-inflammatory
      sensitization; modulating hippocampal neurogenesis; and regulating the microbiome
      brain-gut axis. Finally, we outline current challenges and lay out the future
      directions of taVNS treatment of depression, which include (1) intensively
      comparing stimulation parameters and "dose effect" (treatment frequency and
      duration) to maximize the treatment effect of taVNS; (2) exploring the effect of
      taVNS on disorders comorbid with depression (such as chronic pain disorders,
      cardiovascular disorder, and autism) to provide new "two-for-one" treatment
      approaches for patients with these disorders; and (3) applying multiple scale
      methods to explore the underlying mechanism of taVNS.

PMID- 29459839
TI  - Psychological Characteristics in Talented Soccer Players - Recommendations on How
      to Improve Coaches' Assessment.
AB  - Psychological characteristics, including personality traits and psychological
      skills, have been shown to be relevant predictors of soccer performance. In
      research, general and sport specific standardized self-report questionnaires have
      been applied in psychological diagnostics of sports talent. However, with regard
      to the assessment of psychological characteristics of talented soccer players, a
      gap between research and practice is apparent. While soccer clubs often ask their
      coaches to assess their players on self-designed, unevaluated scouting sheets,
      research widely neglects expert coaches' and clubs' perspectives on relevant
      performance characteristics. As we believe that expert coaches' assessments could
      be a valid predictor of a player's current performance and future success, we
      provide recommendations on how to improve coaches' assessment of psychological
      characteristics. As the quality of the assessment of psychological
      characteristics is crucial, we provide recommendations on how to ensure the
      central diagnostic standards: objectivity, reliability, and validity in talent
      assessment. Further, we argue that assessing psychological characteristics should
      combine self ratings of players and external ratings of coaches in talent
      development. Sport psychologists should assist clubs and coaches in improving the
      diagnostics of psychological characteristics as well as in embedding
      psychological diagnostics and interventions in the talent development process.

PMID- 29459840
TI  - How Strong Is Your Coffee? The Influence of Visual Metaphors and Textual Claims
      on Consumers' Flavor Perception and Product Evaluation.
AB  - This study investigates the relative impact of textual claims and visual
      metaphors displayed on the product's package on consumers' flavor experience and
      product evaluation. For consumers, strength is one of the most important sensory
      attributes of coffee. The 2 * 3 between-subjects experiment (N = 123) compared
      the effects of visual metaphor of strength (an image of a lion located either on
      top or on the bottom of the package of coffee beans) and the direct textual claim
      ("extra strong") on consumers' responses to coffee, including product
      expectation, flavor evaluation, strength perception and purchase intention. The
      results demonstrate that both the textual claim and the visual metaphor can be
      efficient in communicating the product attribute of strength. The presence of the
      image positively influenced consumers' product expectations before tasting. The
      textual claim increased the perception of strength of coffee and the purchase
      intention of the product. The location of the image also played an important role
      in flavor perception and purchase intention. The image located on the bottom of
      the package increased the perceived strength of coffee and purchase intention of
      the product compared to the image on top of the package. This result could be
      interpreted from the perspective of the grounded cognition theory, which suggests
      that a picture in the lower part of the package would automatically activate the
      "strong is heavy" metaphor. As heavy objects are usually associated with a
      position on the ground, this would explain why perceiving a visually heavy
      package would lead to the experience of a strong coffee. Further research is
      needed to better understand the relationships between a metaphorical image and
      its spatial position in food packaging design.

PMID- 29459841
TI  - Electrophysiological Response to the Informative Value of Feedback Revealed in a
      Segmented Wisconsin Card Sorting Test.
AB  - Feedback has two main components. One is valence that indicates the wrong or
      correct behavior, and the other is the informative value that refers to what we
      can learn from feedback. Aimed to explore the neural distinction of these two
      components, we provided participants with a segmented Wisconsin Card Sorting
      Task, in which they received either positive or negative feedback at different
      steps. The informative value was manipulated in terms of the order of feedback
      presentation. The results of event-related potentials time-locked to the feedback
      presentation confirmed that valence of feedback was processed in a broad epoch,
      especially in the time window of feedback-related negativity (FRN), reflecting
      detection of correct or wrong card sorting behavior. In contrast, the informative
      value of positive and negative feedback was mainly processed in the P300,
      possibly reflecting information updating or hypothesis revision. These findings
      provide new evidence that informative values of feedback are processed by
      cognitive systems that differ from those of feedback valence.

PMID- 29459842
TI  - Robot Faces that Follow Gaze Facilitate Attentional Engagement and Increase Their
      Likeability.
AB  - Gaze behavior of humanoid robots is an efficient mechanism for cueing our spatial
      orienting, but less is known about the cognitive-affective consequences of robots
      responding to human directional cues. Here, we examined how the extent to which a
      humanoid robot (iCub) avatar directed its gaze to the same objects as our
      participants affected engagement with the robot, subsequent gaze-cueing, and
      subjective ratings of the robot's characteristic traits. In a gaze-contingent
      eyetracking task, participants were asked to indicate a preference for one of two
      objects with their gaze while an iCub avatar was presented between the object
      photographs. In one condition, the iCub then shifted its gaze toward the object
      chosen by a participant in 80% of the trials (joint condition) and in the other
      condition it looked at the opposite object 80% of the time (disjoint condition).
      Based on the literature in human-human social cognition, we took the speed with
      which the participants looked back at the robot as a measure of facilitated
      reorienting and robot-preference, and found these return saccade onset times to
      be quicker in the joint condition than in the disjoint condition. As indicated by
      results from a subsequent gaze-cueing tasks, the gaze-following behavior of the
      robot had little effect on how our participants responded to gaze cues.
      Nevertheless, subjective reports suggested that our participants preferred the
      iCub following participants' gaze to the one with a disjoint attention behavior,
      rated it as more human-like and as more likeable. Taken together, our findings
      show a preference for robots who follow our gaze. Importantly, such subtle
      differences in gaze behavior are sufficient to influence our perception of
      humanoid agents, which clearly provides hints about the design of behavioral
      characteristics of humanoid robots in more naturalistic settings.

PMID- 29459843
TI  - Hypothesis: The Vestibular and Cerebellar Basis of the Mal de Debarquement
      Syndrome.
AB  - The Mal de Debarquement syndrome (MdDS) generally follows sea voyages, but it can
      occur after turbulent flights or spontaneously. The primary features are
      objective or perceived continuous rocking, swaying, and/or bobbing at 0.2 Hz
      after sea voyages or 0.3 Hz after flights. The oscillations can continue for
      months or years and are immensely disturbing. Associated symptoms appear to be
      secondary to the incessant sensation of movement. We previously suggested that
      the illness can be attributed to maladaptation of the velocity storage integrator
      in the vestibular system, but the actual neural mechanisms driving the MdDS are
      unknown. Here, based on experiments in subhuman primates, we propose a series of
      postulates through which the MdDS is generated: (1) The MdDS is produced in the
      velocity storage integrator by activation of vestibular-only (VO) neurons on
      either side of the brainstem that are oscillating back and forth at 0.2 or 0.3
      Hz. (2) The groups of VO neurons are driven by signals that originate in Purkinje
      cells in the cerebellar nodulus. (3) Prolonged exposure to roll, either on the
      sea or in the air, conditions the roll-related neurons in the nodulus. (4) The
      prolonged exposure causes a shift of the pitch orientation vector from its
      original position aligned with gravity to a position tilted in roll. (5)
      Successful treatment involves exposure to a full-field optokinetic stimulus
      rotating around the spatial vertical countering the direction of the vestibular
      imbalance. This is done while rolling the head at the frequency of the perceived
      rocking, swaying, or bobbing. We also note experiments that could be used to
      verify these postulates, as well as considering potential flaws in the logic.
      Important unanswered questions: (1) Why does the MdDS predominantly affect women?
      (2) What aspect of roll causes the prolongation of the tilted orientation vector,
      and why is it so prolonged in some individuals? (3) What produces the increase in
      symptoms of some patients when returning home after treatment, and how can this
      be avoided? We also posit that the same mechanisms underlie the less troublesome
      and shorter duration Mal de Debarquement.

PMID- 29459844
TI  - Magnetic Resonance Spectroscopy, Positron Emission Tomography and Radiogenomics
      Relevance to Glioma.
AB  - Advances in metabolic imaging techniques have allowed for more precise
      characterization of gliomas, particularly as it relates to tumor recurrence or
      pseudoprogression. Furthermore, the emerging field of radiogenomics where
      radiographic features are systemically correlated with molecular markers has the
      potential to achieve the holy grail of neuro-oncologic neuro-radiology, namely
      molecular diagnosis without requiring tissue specimens. In this section, we will
      review the utility of metabolic imaging and discuss the current state of the art
      related to the radiogenomics of glioblastoma.

PMID- 29459845
TI  - Levodopa-Induced Changes in Electromyographic Patterns in Patients with Advanced
      Parkinson's Disease.
AB  - Levodopa medication is the most efficient treatment for motor symptoms of
      Parkinson's disease (PD). Levodopa significantly alleviates rigidity, rest
      tremor, and bradykinesia in PD. The severity of motor symptoms can be graded with
      UPDRS-III scale. Levodopa challenge test is routinely used to assess patients'
      eligibility to deep-brain stimulation (DBS) in PD. Feasible and objective
      measurements to assess motor symptoms of PD during levodopa challenge test would
      be helpful in unifying the treatment. Twelve patients with advanced PD who were
      candidates for DBS treatment were recruited to the study. Measurements were done
      in four phases before and after levodopa challenge test. Rest tremor and rigidity
      were evaluated using UPDRS-III score. Electromyographic (EMG) signals from biceps
      brachii and kinematic signals from forearm were recorded with wireless
      measurement setup. The patients performed two different tasks: arm isometric
      tension and arm passive flexion-extension. The electromyographic and the
      kinematic signals were analyzed with parametric, principal component, and
      spectrum-based approaches. The principal component approach for isometric tension
      EMG signals showed significant decline in characteristics related to PD during
      levodopa challenge test. The spectral approach on passive flexion-extension EMG
      signals showed a significant decrease on involuntary muscle activity during the
      levodopa challenge test. Both effects were stronger during the levodopa challenge
      test compared to that of patients' personal medication. There were no significant
      changes in the parametric approach for EMG and kinematic signals during the
      measurement. The results show that a wireless and wearable measurement and
      analysis can be used to study the effect of levodopa medication in advanced
      Parkinson's disease.

PMID- 29459846
TI  - Vestibular Dysfunctions in Sudden Sensorineural Hearing Loss: A Systematic Review
      and Meta-analysis.
AB  - Background: Sudden sensorineural hearing loss (SSHL) not only involves cochlear
      function but might also be accompanied by vestibular disturbances. The assessment
      of vestibular function could be of great relevance in SSHL. Objective: To
      investigate the prevalence of vestibulocochlear lesions in SSHL and the
      correlation of specific vestibular organs with hearing prognosis. Data sources: A
      complete literature search of eligible studies in the PubMed and EMBASE databases
      was performed. Study selection: For our aim, studies that focused on vestibular
      examination in the case of SSHL were retrieved, including caloric tests, cervical
      vestibular-evoked myogenic potential (cVEMP) tests, or ocular vestibular-evoked
      myogenic potential (oVEMP) tests. Results: Of the 18 studies included, a caloric
      test was performed in 16 studies, cVEMP in 13 studies, and oVEMP in 5 studies,
      and together the studies included a total population of 1,468 subjects. The
      scores on the Agency for Healthcare Research and Quality (AHRQ) questionnaire
      ranged from 6 to 11. These results indicated that the most commonly damaged
      vestibular organ in SSHL was the utricle and superior vestibular pathway (U + S)
      followed by the lateral semicircular canal and superior vestibular pathway (LSC +
      S), the saccule and inferior vestibular pathway (S + I), and the cochlea only (C
      only). The meta-analysis indicated that SSHL patients with vertigo have a
      statistically increased risk of vestibular organ lesions compared with those
      without vertigo, including the LSC + S subgroup (OR = 4.89, 95% CI = 1.20-19.93,
      I2 = 80%, p = 0.03) and the S + I subgroup (OR = 3.58, 95% CI = 1.61-7.95, I2 =
      0%, p = 0.002). The pooled possibility of hearing recovery within the LSC + S
      lesion group was less than half that of the non-LSC + S lesion group (OR = 0.24,
      95% CI = 0.11-0.52, I2 = 68%, p = 0.0003). Conclusion: This study shows the
      relevance of vestibular damage concomitant with SSHL and that SSHL patients with
      vertigo are at an increased risk of vestibular organ lesions compared with
      patients without vertigo. LSC + S lesions thus appear to be a critical variable
      that influence the possibility of hearing improvement in SSHL.

PMID- 29459848
TI  - Commentary: Pitfalls in the Neuroimaging of Glioblastoma in the Era of
      Antiangiogenic and Immuno/Targeted Therapy.

PMID- 29459847
TI  - Novel Approaches to the Diagnosis of Chronic Disorders of Consciousness:
      Detecting Peripersonal Space by Using Ultrasonics.
AB  - The assessment of behavioral responsiveness in patients suffering from chronic
      disorders of consciousness (DoC), including Unresponsive Wakefulness Syndrome
      (UWS) and Minimally Conscious State (MCS), is challenging. Even if a patient is
      unresponsive, he/she may be covertly aware in reason of a cognitive-motor
      dissociation, i.e., a preservation of cognitive functions despite a solely
      reflexive behavioral responsiveness. The approach of an external stimulus to the
      peripersonal space (PPS) modifies some biological measures (e.g., hand-blink
      reflex amplitude) to the purpose of defensive responses from threats. Such
      modulation depends on a top-down control of subcortical neural circuits, which
      can be explored through changes in cerebral blood flow velocity (CBFV), using
      functional transcranial Doppler (fTCD) and, thus, gaining useful, indirect
      information on brain connectivity. These data may be used for the DoC
      differential diagnosis. We evaluated the changes in CBFV by measuring the
      pulsatility index (PI) in 21 patients with DoC (10 patients with MCS and 11 with
      UWS) and 25 healthy controls (HC) during a passive movement and motor imagery
      (MI) task in which the hand of the subject approached and, then, moved away from
      the subject's face. In the passive movement task, the PI increased progressively
      in the HCs when the hand was moved toward the face and, then, it decreased when
      the hand was removed from the face. The PI increased when the hand was moved
      toward the face in patients with DoC, but then, it remained high when the hand
      was removed from the face and up to 30 s after the end of the movement in the
      patients with MCS (both MCS+ and MCS-) and 1 min in those with UWS, thus
      differentiating between patients with MCS and UWS. In the MI task, all the HCs,
      three out of four patients with MCS+, and one out of six patients with MCS-
      showed an increase-decrease PI change, whereas the remaining patients with MCS
      and all the patients with UWS showed no PI changes. Even though there is the
      possibility that our findings will not be replicated in all patients with DoC, we
      propose fTCD as a rapid and very easy tool to differentiate between patients with
      MCS and UWS, by identifying residual top-down modulation processes from higher
      order cortical areas to sensory-motor integration networks related to the PPS,
      when using passive movement tasks.

PMID- 29459849
TI  - Widely Used Commercial ELISA Does Not Detect Precursor of Haptoglobin2, but
      Recognizes Properdin as a Potential Second Member of the Zonulin Family.
AB  - Background: There is increasing evidence for the role of impaired intestinal
      permeability in obesity and associated metabolic diseases. Zonulin is an
      established serum marker for intestinal permeability and identical to pre
      haptoglobin2. Here, we aimed to investigate the relationship between circulating
      zonulin and metabolic traits related to obesity. Methods: Serum zonulin was
      measured by using a widely used commercial ELISA kit in 376 subjects from the
      metabolically well-characterized cohort of Sorbs from Germany. In addition,
      haptoglobin genotype was determined in DNA samples from all study subjects.
      Results: As zonulin concentrations did not correlate to the haptoglobin
      genotypes, we investigated the specificity of the zonulin ELISA assay using
      antibody capture experiments, mass spectrometry, and Western blot analysis. Using
      serum samples that gave the highest or lowest ELISA signals, we detected several
      proteins that are likely to be captured by the antibody in the present kit.
      However, none of these proteins corresponds to pre-haptoglobin2. We used
      increasing concentrations of recombinant pre-haptoglobin2 and complement C3 as
      one of the representative captured proteins and the ELISA kit did not detect
      either. Western blot analysis using both the polyclonal antibodies used in this
      kit and monoclonal antibodies rose against zonulin showed a similar protein
      recognition pattern but with different intensity of detection. The protein(s)
      measured using the ELISA kit was (were) significantly increased in patients with
      diabetes and obesity and correlated strongly with markers of the lipid and
      glucose metabolism. Combining mass spectrometry and Western blot analysis using
      the polyclonal antibodies used in the ELISA kit, we identified properdin as
      another member of the zonulin family. Conclusion: Our study suggests that the
      zonulin ELISA does not recognize pre-haptoglobin2, rather structural (and
      possibly functional) analog proteins belonging to the mannose-associated serine
      protease family, with properdin being the most likely possible candidate.

PMID- 29459850
TI  - Bacterial Seed Endophytes of Domesticated Cucurbits Antagonize Fungal and
      Oomycete Pathogens Including Powdery Mildew.
AB  - The cucurbit vegetables, including cucumbers, melons and pumpkins, have been
      cultivated for thousands of years without fungicides. However, their seed
      germination stage is prone to be infected by soil-borne fungal and oomycete
      pathogens. Endophytes are symbionts that reside inside plant tissues including
      seeds. Seed endophytes are founders of the juvenile plant microbiome and can
      promote host defense at seed germination and later stages. We previously isolated
      169 bacterial endophytes associated with seeds of diverse cultivated cucurbits.
      We hypothesized that these endophytes can antagonize major fungal and oomycete
      pathogens. Here we tested the endophytes for in vitro antagonism (dual culture
      assays) against important soil-borne pathogens (Rhizoctonia solani, Fusarium
      graminearum, Phytophthora capsici, Pythium aphanideratum). The endophytes were
      also assayed in planta (leaf disk and detached leaf bioassays) for antagonism
      against a foliar pathogen of global importance, Podosphaera fuliginea, the
      causative agent of cucurbit powdery mildew. The endophytes were further tested in
      vitro for secretion of volatile organic compounds (VOCs) known to induce plant
      defense. Extracellular ribonuclease activity was also tested, as a subset of
      pathogenesis-related (PR) proteins of plant hosts implicated in suppression of
      fungal pathogens, displays ribonuclease activity. An unexpected majority of the
      endophytes (70%, 118/169) exhibited antagonism to the five phytopathogens, of
      which 68% (50/73) of in vitro antagonists belong to the genera Bacillus and
      Paenibacillus. All Lactococcus and Pantoea endophytes exhibited anti-oomycete
      activity. However, amongst the most effective inoculants against Podosphaera
      fuliginea were Pediococcus and Pantoea endophytes. Interestingly, 67% (113/169)
      of endophytes emitted host defense inducing VOCs (acetoin/diacetyl) and 62%
      (104/169) secreted extracellular ribonucleases in vitro, respectively. These
      results show that seeds of cultivated cucurbits package microbes with significant
      disease-suppression potential. As seeds can act as vectors for genetic
      transmission of endophytes across host generations, it is interesting to
      hypothesize whether humans, when selecting seeds of healthy hosts, may have
      inadvertently selected for disease-suppressing seed endophytes. As the majority
      of pathogen-suppressing endophytes belong to Bacillus and Paenibacillus, and
      since Bacilli are widely used as commercial biocontrol agents of vegetables, we
      propose that these agents are mimicking the ecological niche established by their
      endophytic cousins.

PMID- 29459851
TI  - Dynamics of Metabolite Induction in Fungal Co-cultures by Metabolomics at Both
      Volatile and Non-volatile Levels.
AB  - Fungal co-cultivation has emerged as a promising way for activating cryptic
      biosynthetic pathways and discovering novel antimicrobial metabolites. For the
      success of such studies, a key element remains the development of standardized co
      cultivation methods compatible with high-throughput analytical procedures. To
      efficiently highlight induction processes, it is crucial to acquire a holistic
      view of intermicrobial communication at the molecular level. To tackle this
      issue, a strategy was developed based on the miniaturization of fungal cultures
      that allows for a concomitant survey of induction phenomena in volatile and non
      volatile metabolomes. Fungi were directly grown in vials, and each sample was
      profiled by head space solid phase microextraction gas chromatography mass
      spectrometry (HS-SPME-GC-MS), while the corresponding solid culture medium was
      analyzed by liquid chromatography high resolution mass spectrometry (LC-HRMS)
      after solvent extraction. This strategy was implemented for the screening of
      volatile and non-volatile metabolite inductions in an ecologically relevant
      fungal co-culture of Eutypa lata (Pers.) Tul. & C. Tul. (Diatrypaceae) and
      Botryosphaeria obtusa (Schwein.) Shoemaker (Botryosphaeriaceae), two wood
      decaying fungi interacting in the context of esca disease of grapevine. For a
      comprehensive evaluation of the results, a multivariate data analysis combining
      Analysis of Variance and Partial Least Squares approaches, namely AMOPLS, was
      used to explore the complex LC-HRMS and GC-MS datasets and highlight dynamically
      induced compounds. A time-series study was carried out over 9 days, showing
      characteristic metabolite induction patterns in both volatile and non-volatile
      dimensions. Relevant links between the dynamics of expression of specific
      metabolite production were observed. In addition, the antifungal activity of 2
      nonanone, a metabolite incrementally produced over time in the volatile fraction,
      was assessed against Eutypa lata and Botryosphaeria obtusa in an adapted bioassay
      set for volatile compounds. This compound has shown antifungal activity on both
      fungi and was found to be co-expressed with a known antifungal compound, O
      methylmellein, induced in solid media. This strategy could help elucidate
      microbial inter- and intra-species cross-talk at various levels. Moreover, it
      supports the study of concerted defense/communication mechanisms for efficiently
      identifying original antimicrobials.

PMID- 29459852
TI  - beta-HPV Infection Correlates with Early Stages of Carcinogenesis in Skin Tumors
      and Patient-Derived Xenografts from a Kidney Transplant Recipient Cohort.
AB  - Many malignancies that occur in high excess in kidney transplant recipients
      (KTRs) are due to viruses that thrive in the setting of immunosuppression.
      Keratinocyte carcinoma (KC), the most frequently occurring cancer type in KTR,
      has been associated with skin infection by human papillomavirus (HPV) from the
      beta genus. In this report, we extend our previous investigation aimed at
      identifying the presence of active beta-HPV infection in skin tumors from KTRs
      through detection of viral protein expression. Using a combination of antibodies
      raised against the E4 and L1 proteins of the beta-genotypes, we were able to
      visualize infection in five tumors [one keratoacanthoma (KA), three actinic
      keratoses (AKs), and one seborrheic keratoses (SKs)] that were all removed from
      two patients who had been both transplanted twice, had developed multiple KCs,
      and presented with a long history of immunosuppression (>30 years). These
      infected tissues displayed intraepidermal hyperplasia and increased expression of
      the DeltaNp63 protein, which extended into the upper epithelial layers. In
      addition, using a xenograft model system in nude mice displaying a humanized
      stromal bed in the site of grafting, we successfully engrafted three AKs, two of
      which were derived from the aforementioned KTRs and displayed beta-HPV infection
      in the original tumor. Of note, one AK-derived xenograft, along with its ensuing
      lymph node metastasis, was diagnosed as squamous cell carcinoma (SCC). In the
      latter, both beta-HPV infection and DeltaNp63 expression were no longer
      detectable. Although the overall success rate of engrafting was very low, the
      results of this study show for the first time that beta-HPV+ and DeltaNp63+
      intraepidermal hyperplasia can indeed progress to an aggressive SCC able to
      metastasize. Consistent with a series of reports attributing a causative role of
      beta-HPV at early stages of skin carcinogenesis through DeltaNp63 induction and
      increased keratinocytes stemness, here we provide in vivo evidence that these
      events are also occurring in the affected skin of KTRs. Due to these beta-HPV
      driven molecular pathways, the nascent tumor cell is able to acquire a high
      enough number of carcinogenic insults that its proliferation and survival will
      eventually become independent of viral gene expression.

PMID- 29459853
TI  - Does Treatment Order Matter? Investigating the Ability of Bacteriophage to
      Augment Antibiotic Activity against Staphylococcus aureus Biofilms.
AB  - The inability to effectively treat biofilm-related infections is a major clinical
      challenge. This has been attributed to the heightened antibiotic tolerance
      conferred to bacterial cells embedded within biofilms. Lytic bacteriophages
      (phages) have evolved to effectively infect and eradicate biofilm-associated
      cells. The current study was designed to investigate the ability of phage
      treatment to enhance the activity of antibiotics against biofilm-forming
      Staphylococcus aureus. The biofilm positive S. aureus strain ATCC 35556, the
      lytic S. aureus phage SATA-8505, and five antibiotics (cefazolin, vancomycin,
      dicloxacillin, tetracycline, and linezolid), used to treat S. aureus infections,
      were tested in this study. The ability of the SATA-8505 phage to augment the
      effect of these antibiotics against biofilm-associated S. aureus cells was
      assessed by exposing them to one of the five following treatment strategies: (i)
      antibiotics alone, (ii) phage alone, (iii) a combination of the two treatments
      simultaneously, (iv) staggered exposure to the phage followed by antibiotics, and
      (v) staggered exposure to antibiotics followed by exposure to phage. The effect
      of each treatment strategy on biofilm cells was assessed by enumerating viable
      bacterial cells. The results demonstrate that the treatment of biofilms with
      either SATA-8505, antibiotics, or both simultaneously resulted in minimal
      reduction of viable biofilm-associated cells. However, a significant reduction
      [up to 3 log colony forming unit (CFU)/mL] was observed when the phage treatment
      preceded antibiotics. This effect was most pronounced with vancomycin and
      cefazolin which exhibited synergistic interactions with SATA-8505, particularly
      at lower antibiotic concentrations. This in vitro study provides proof of
      principle for the ability of phages to augment the activity of antibiotics
      against S. aureus biofilms. Our results also demonstrate that therapeutic
      outcomes can be influenced by the sequence in which these therapeutic agents are
      administered, and the nature of their interactions. Further investigation into
      the interactions between lytic phages and antibiotics against various biofilm
      forming organisms is important to direct future clinical translation of
      efficacious antibiotic-phage combination therapeutic strategies.

PMID- 29459854
TI  - The Glutaredoxin Gene, grxB, Affects Acid Tolerance, Surface Hydrophobicity, Auto
      Aggregation, and Biofilm Formation in Cronobacter sakazakii.
AB  - Cronobacter species are foodborne pathogens that can cause neonatal meningitis,
      necrotizing enterocolitis, and sepsis; they have unusual abilities to survive in
      environmental stresses such as acid stress. However, the factors involved in acid
      stress responses and biofilm formation in Cronobacter species are poorly
      understood. In this study, we investigated the role of grxB on cellular
      morphology, acid tolerance, surface hydrophobicity, auto-aggregation (AAg),
      motility, and biofilm formation in Cronobacter sakazakii. The deletion of grxB
      decreased resistance to acid stresses, and notably led to weaker surface
      hydrophobicity, AAg, and biofilm formation under normal and acid stress
      conditions, compared with those of the wild type strain; however, motility was
      unaffected. Therefore, grxB appears to contribute to the survival of C. sakazakii
      in acid stresses and biofilm formation. This is the first report to provide
      valuable evidence for the role of grxB in acid stress responses and biofilm
      formation in C. sakazakii.

PMID- 29459855
TI  - Severity of Systemic Inflammatory Response Syndrome Affects the Blood Levels of
      Circulating Inflammatory-Relevant MicroRNAs.
AB  - The systemic inflammatory response syndrome (SIRS) is a potentially lethal
      response triggered by diverse forms of tissue injury and infection. When systemic
      inflammation is triggered by infection, the term sepsis is used. Understanding
      how inflammation is mediated and regulated is of enormous medical importance. We
      previously demonstrated that circulating inflammatory-relevant microRNAs (CIR
      miRNAs) are candidate biomarkers for differentiating sepsis from SIRS. Here, we
      set out to determine how CIR-miRNA levels reflect SIRS severity and whether they
      derive from activated immune cells. Clinical disease severity scores and markers
      of red blood cell (RBC) damage or immune cell activation were correlated with CIR
      miRNA levels in patients with SIRS and sepsis. The release of CIR-miRNAs
      modulated during SIRS was assessed in immune cell cultures. We show that severity
      of non-infective SIRS, but not sepsis is reflected in the levels of miR-378a-3p,
      miR-30a-5p, miR-30d-5p, and miR-192-5p. These CIR-miRNA levels positively
      correlate with levels of the redox biomarker, peroxiredoxin-1 (Prdx-1), which has
      previously been shown to be released by immune cells during inflammation.
      Furthermore, in vitro activated immune cells produce SIRS-associated miR-378a-3p,
      miR-30a-5p, miR-30d-5p, and miR-192-5p. Our study furthers the understanding of
      the origin, role, and trafficking of CIR-miRNAs as potential regulators of
      inflammation.

PMID- 29459856
TI  - The Immune and Non-Immune Pathways That Drive Chronic Gastrointestinal Helminth
      Burdens in the Wild.
AB  - Parasitic helminths are extremely resilient in their ability to maintain chronic
      infection burdens despite (or maybe because of) their hosts' immune response.
      Explaining how parasites maintain these lifelong infections, identifying the
      protective immune mechanisms that regulate helminth infection burdens, and
      designing prophylactics and therapeutics that combat helminth infection, while
      preserving host health requires a far better understanding of how the immune
      system functions in natural habitats than we have at present. It is, therefore,
      necessary to complement mechanistic laboratory-based studies with studies on wild
      populations and their natural parasite communities. Unfortunately, the relative
      paucity of immunological tools for non-model species has held these types of
      studies back. Thankfully, recent progress in high-throughput 'omics platforms
      provide powerful and increasingly practical means for immunologists to move
      beyond traditional lab-based model organisms. Yet, assigning both metabolic and
      immune function to genes, transcripts, and proteins in novel species and
      assessing how they interact with other physiological and environmental factors
      requires identifying quantitative relationships between their expression and
      infection. Here, we used supervised machine learning to identify gene networks
      robustly associated with burdens of the gastrointestinal nematode Heligmosomoides
      polygyrus in its natural host, the wild wood mice Apodemus sylvaticus. Across 34
      mice spanning two wild populations and across two different seasons, we found
      17,639 transcripts that clustered in 131 weighted gene networks. These clusters
      robustly predicted H. polygyrus burden and included well-known effector and
      regulatory immune genes, but also revealed a number of genes associated with the
      maintenance of tissue homeostasis and hematopoiesis that have so far received
      little attention. We then tested the effect of experimentally reducing helminth
      burdens through drug treatment on those putatively protective immune factors.
      Despite the near elimination of H. polygyrus worms, the treatment had
      surprisingly little effect on gene expression. Taken together, these results
      suggest that hosts balance tissue homeostasis and protective immunity, resulting
      in relatively stable immune and, consequently, parasitological profiles. In the
      future, applying our approach to larger numbers of samples from additional
      populations will help further increase our ability to detect the immune pathways
      that determine chronic gastrointestinal helminth burdens in the wild.

PMID- 29459857
TI  - Genome-Wide Bimolecular Fluorescence Complementation-Based Proteomic Analysis of
      Toxoplasma gondii ROP18's Human Interactome Shows Its Key Role in Regulation of
      Cell Immunity and Apoptosis.
AB  - Toxoplasma gondii rhoptry protein ROP18 (TgROP18) is a key virulence factor
      secreted into the host cell during invasion, where it modulates the host cell
      response by interacting with its host targets. However, only a few TgROP18
      targets have been identified. In this study, we applied a high-throughput protein
      protein interaction (PPI) screening in human cells using bimolecular fluorescence
      complementation (BiFC) to identify the targets of Type I strain ROP18 (ROP18I)
      and Type II strain ROP18 (ROP18II). From a pool of more than 18,000 human
      proteins, 492 and 141 proteins were identified as the targets of ROP18I and
      ROP18II, respectively. Gene ontology, search tool for the retrieval of
      interacting genes/proteins PPI network, and Ingenuity pathway analyses revealed
      that the majority of these proteins were associated with immune response and
      apoptosis. This indicates a key role of TgROP18 in manipulating host's immunity
      and cell apoptosis, which might contribute to the immune escape and successful
      parasitism of the parasite. Among the proteins identified, the immunity-related
      proteins N-myc and STAT interactor, IL20RB, IL21, ubiquitin C, and vimentin and
      the apoptosis-related protein P2RX1 were further verified as ROP18I targets by
      sensitized emission-fluorescence resonance energy transfer (SE-FRET) and co
      immunoprecipitation. Our study substantially contributes to the current limited
      knowledge on human targets of TgROP18 and provides a novel tool to investigate
      the function of parasite effectors in human cells.

PMID- 29459858
TI  - Type I Interferon Signaling Is Required for CpG-Oligodesoxynucleotide-Induced
      Control of Leishmania major, but Not for Spontaneous Cure of Subcutaneous Primary
      or Secondary L. major Infection.
AB  - We previously showed that in mice infected with Leishmania major type I
      interferons (IFNs) initiate the innate immune response to the parasite at day 1
      and 2 of infection. Here, we investigated which type I IFN subtypes are expressed
      during the first 8 weeks of L. major infection and whether type I IFNs are
      essential for a protective immune response and clinical cure of the disease. In
      self-healing C57BL/6 mice infected with a high dose of L. major, IFN-alpha4, IFN
      alpha5, IFN-alpha11, IFN-alpha13, and IFN-beta mRNA were most prominently
      regulated during the course of infection. In C57BL/6 mice deficient for IFN-beta
      or the IFN-alpha/beta-receptor chain 1 (IFNAR1), development of skin lesions and
      parasite loads in skin, draining lymph node, and spleen was indistinguishable
      from wild-type (WT) mice. In line with the clinical findings, C57BL/6 IFN-beta-/
      , IFNAR1-/-, and WT mice exhibited similar mRNA expression levels of IFN-gamma,
      interleukin (IL)-4, IL-12, IL-13, inducible nitric oxide synthase, and arginase 1
      during the acute and late phase of the infection. Also, myeloid dendritic cells
      from WT and IFNAR1-/- mice produced comparable amounts of IL-12p40/p70 protein
      upon exposure to L. major in vitro. In non-healing BALB/c WT mice, the mRNAs of
      IFN-alpha subtypes (alpha2, alpha4, alpha5, alpha6, and alpha9) were rapidly
      induced after high-dose L. major infection. However, genetic deletion of IFNAR1
      or IFN-beta did not alter the progressive course of infection seen in WT BALB/c
      mice. Finally, we tested whether type I IFNs and/or IL-12 are required for the
      prophylactic effect of CpG-oligodesoxynucleotides (ODN) in BALB/c mice. Local and
      systemic administration of CpG-ODN 1668 protected WT and IFN-beta-/- mice equally
      well from progressive leishmaniasis. By contrast, the protective effect of CpG
      ODN 1668 was lost in BALB/c IFNAR1-/- (despite a sustained suppression of IL-4)
      and in BALB/c IL-12p35-/- mice. From these data, we conclude that IFN-beta and
      IFNAR1 signaling are dispensable for a curative immune response to L. major in
      C57BL/6 mice and irrelevant for disease development in BALB/c mice, whereas IL-12
      and IFN-alpha subtypes are essential for the disease prevention by CpG-ODNs in
      this mouse strain.

PMID- 29459860
TI  - Humoral Responses Elicited by Adenovirus Displaying Epitopes Are Induced
      Independently of the Infection Process and Shaped by the Toll-Like Receptor/MyD88
      Pathway.
AB  - The use of serotype 5 adenovirus (Ad)-derived vectors in vaccination is
      confronted to preexisting anti-Ad immunity. Epitope display on Ad capsid is
      currently being investigated as an alternative approach of vaccination. The
      present study seeks to better understand virus- and host-related factors
      controlling the efficacy of this new vaccination approach. In contrast to an Ad
      vector expressing ovalbumin as a transgene, Ad displaying an ovalbumin-derived B
      cell epitope inserted into the fiber protein was able to elicit antibody
      responses in both Ad-naive and Ad-immune mice. Moreover, introduction of a set of
      mutations abrogating Ad interaction with its receptors did not modify the virus
      capacity to elicit a humoral response against the inserted epitope while reducing
      its capacity to mount antibody responses against the transgene product. Taken as
      a whole these data indicate that the efficacy of Ad displaying epitopes requires
      neither Ad binding to its receptors nor the infection process. In addition, the
      use of genetically deficient mice demonstrated that both toll-like receptor
      (TLR)/MyD88 and RIG-I/mitochondrial antiviral-signaling (MAVS) innate immunity
      pathways were dispensable to mount anti-epitope antibody responses. However, they
      also revealed that TLR/MyD88 pathway but not RIG-I/MAVS pathway controls the
      nature of antibodies directed against the displayed epitope.

PMID- 29459859
TI  - Next-Generation Vaccines Based on Bacille Calmette-Guerin.
AB  - Tuberculosis (TB), caused by the intracellular bacterium Mycobacterium
      tuberculosis (Mtb), remains a major health threat. A live, attenuated
      mycobacterium known as Bacille Calmette-Guerin (BCG), derived from the causative
      agent of cattle TB, Mycobacterium bovis, has been in clinical use as a vaccine
      for 90 years. The current incidence of TB demonstrates that BCG fails to protect
      sufficiently against pulmonary TB, the major disease manifestation and source of
      dissemination. The protective efficacy of BCG is on average 50% but varies
      substantially with geographical location and is poorer in those with previous
      exposure to mycobacteria. BCG can also cause adverse reactions in
      immunocompromised individuals. However, BCG has contributed to reduced infant TB
      mortality by protecting against extrapulmonary TB. In addition, BCG has been
      associated with reduced general childhood mortality by stimulating immune
      responses. In order to improve the efficacy of BCG, two major strategies have
      been employed. The first involves the development of recombinant live
      mycobacterial vaccines with improved efficacy and safety. The second strategy is
      to boost BCG with subunit vaccines containing Mtb antigens. This article reviews
      recombinant BCG strains that have been tested against TB in animal models. This
      includes BCG strains that have been engineered to induce increased immune
      responses by the insertion of genes for Mtb antigens, mammalian cytokines, or
      host resistance factors, the insertion of bacterial toxin-derived adjuvants, and
      the manipulation of bacterial genes in order to increase antigen presentation and
      immune activation. Subunit vaccines for boosting BCG are also briefly discussed.

PMID- 29459861
TI  - In-Depth Analysis of Human Neonatal and Adult IgM Antibody Repertoires.
AB  - Although high-throughput sequencing and associated bioinformatics technologies
      have enabled the in-depth, sequence-based characterization of human immune
      repertoires, only a few studies on a relatively small number of sequences
      explored the characteristics of antibody repertoires in neonates, with
      contradictory conclusions. To gain a more comprehensive understanding of the
      human IgM antibody repertoire, we performed Illumina sequencing and IMGT/HighV
      QUEST analysis of IgM heavy chain repertoire of the B lymphocytes from the cord
      blood (CB) of neonates, as well as the repertoire from peripheral blood of
      healthy human adults (HH). The comparative study revealed unexpectedly high
      levels of similarity between the neonatal and adult repertoires. In both
      repertoires, the VDJ gene usage showed no significant difference, and the most
      frequently used VDJ gene was IGHV4-59, IGHD3-10, and IGHJ3. The average amino
      acid (aa) length of CDR1 (CB: 8.5, HH: 8.4) and CDR2 (CB: 7.6, HH: 7.5), as well
      as the aa composition and the average hydrophobicity of the CDR3 demonstrated no
      significant difference between the two repertories. However, the average aa
      length of CDR3 was longer in the HH repertoire than the CB repertoire (CB: 14.5,
      HH: 15.5). Besides, the frequencies of aa mutations in CDR1 (CB: 19.33%, HH:
      25.84%) and CDR2 (CB: 9.26%, HH: 17.82%) were higher in the HH repertoire
      compared to the CB repertoire. Interestingly, the most prominent difference
      between the two repertoires was the occurrence of N2 addition (CB: 64.87%, HH:
      85.69%), a process that occurs during V-D-J recombination for introducing random
      nucleotide additions between D- and J-gene segments. The antibody repertoire of
      healthy adults was more diverse than that of neonates largely due to the higher
      occurrence of N2 addition. These findings may lead to a better understanding of
      antibody development and evolution pathways and may have potential practical
      value for facilitating the generation of more effective antibody therapeutics and
      vaccines.

PMID- 29459862
TI  - Immunotherapy for Dogs: Running Behind Humans.
AB  - A number of excellent reviews on the potential of canine cancer immunotherapy are
      available, but many extrapolate from observations in humans when in fact only
      very few immunotherapies have been developed for canines that have shown efficacy
      in well-designed studies. Pharmaceutical and biotech companies are aware that the
      market for more expensive immunotherapies in canines is limited resulting in
      limited funding for clinical trials. However, dogs and other pets deserve access
      to this new form of cancer therapy. The purpose of this brief review is to
      summarize the current status of available immunotherapies for dogs and their near
      term prospects, provided we can effectively translate discoveries and progress in
      humans to canines.

PMID- 29459863
TI  - A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in
      Innate Immunity and Inflammation.
AB  - Metabolism in immune cells is no longer thought of as merely a process for
      adenosine triphosphate (ATP) production, biosynthesis, and catabolism. The
      reprogramming of metabolic pathways upon activation is also for the production of
      metabolites that can act as immune signaling molecules. Activated dendritic cells
      (DCs) and macrophages have an altered Krebs cycle, one consequence of which is
      the accumulation of both citrate and succinate. Citrate is exported from the
      mitochondria via the mitochondrial citrate- carrier. Cytosolic metabolism of
      citrate to acetyl-coenzyme A (acetyl-CoA) is important for both fatty-acid
      synthesis and protein acetylation, both of which have been linked to macrophage
      and DC activation. Citrate-derived itaconate has a direct antibacterial effect
      and also has been shown to act as an anti-inflammatory agent, inhibiting
      succinate dehydrogenase. These findings identify citrate as an important
      metabolite for macrophage and DC effector function.

PMID- 29459864
TI  - Blood CXCR3+ CD4 T Cells Are Enriched in Inducible Replication Competent HIV in
      Aviremic Antiretroviral Therapy-Treated Individuals.
AB  - We recently demonstrated that lymph nodes (LNs) PD-1+/T follicular helper (Tfh)
      cells from antiretroviral therapy (ART)-treated HIV-infected individuals were
      enriched in cells containing replication competent virus. However, the
      distribution of cells containing inducible replication competent virus has been
      only partially elucidated in blood memory CD4 T-cell populations including the
      Tfh cell counterpart circulating in blood (cTfh). In this context, we have
      investigated the distribution of (1) total HIV-infected cells and (2) cells
      containing replication competent and infectious virus within various blood and LN
      memory CD4 T-cell populations of conventional antiretroviral therapy (cART)
      treated HIV-infected individuals. In the present study, we show that blood CXCR3
      expressing memory CD4 T cells are enriched in cells containing inducible
      replication competent virus and contributed the most to the total pool of cells
      containing replication competent and infectious virus in blood. Interestingly,
      subsequent proviral sequence analysis did not indicate virus compartmentalization
      between blood and LN CD4 T-cell populations, suggesting dynamic interchanges
      between the two compartments. We then investigated whether the composition of
      blood HIV reservoir may reflect the polarization of LN CD4 T cells at the time of
      reservoir seeding and showed that LN PD-1+ CD4 T cells of viremic untreated HIV
      infected individuals expressed significantly higher levels of CXCR3 as compared
      to CCR4 and/or CCR6, suggesting that blood CXCR3-expressing CD4 T cells may
      originate from LN PD-1+ CD4 T cells. Taken together, these results indicate that
      blood CXCR3-expressing CD4 T cells represent the major blood compartment
      containing inducible replication competent virus in treated aviremic HIV-infected
      individuals.

PMID- 29459865
TI  - The Role of Mst1 in Lymphocyte Homeostasis and Function.
AB  - The Hippo pathway is an evolutionarily conserved pathway crucial for regulating
      tissue size and for limiting cancer development. However, recent work has also
      uncovered key roles for the mammalian Hippo kinases, Mst1/2, in driving
      appropriate immune responses by directing T cell migration, morphology, survival,
      differentiation, and activation. In this review, we discuss the classical
      signaling pathways orchestrated by the Hippo signaling pathway, and describe how
      Mst1/2 direct T cell function by mechanisms not seeming to involve the classical
      Hippo pathway. We also discuss why Mst1/2 might have different functions within
      organ systems and the immune system. Overall, understanding how Mst1/2 transmit
      signals to discrete biological processes in different cell types might allow for
      the development of better drug therapies for the treatments of cancers and immune
      related diseases.

PMID- 29459866
TI  - Current Status of Gene Engineering Cell Therapeutics.
AB  - Ex vivo manipulations of autologous patient's cells or gene-engineered cell
      therapeutics have allowed the development of cell and gene therapy approaches to
      treat otherwise incurable diseases. These modalities of personalized medicine
      have already shown great promises including product commercialization for some
      rare diseases. The transfer of a chimeric antigen receptor or T cell receptor
      genes into autologous T cells has led to very promising outcomes for some
      cancers, and particularly for hematological malignancies. In addition, gene
      engineered cell therapeutics are also being explored to induce tolerance and
      regulate inflammation. Here, we review the latest gene-engineered cell
      therapeutic approaches being currently explored to induce an efficient immune
      response against cancer cells or viruses by engineering T cells, natural killer
      cells, gamma delta T cells, or cytokine-induced killer cells and to modulate
      inflammation using regulatory T cells.

PMID- 29459868
TI  - Characteristics of Infection Immunity Regulated by Toxoplasma gondii to Maintain
      Chronic Infection in the Brain.
AB  - To examine the immune environment of chronic Toxoplasma gondii infection in the
      brain, the characteristics of infection-immunity (premunition) in infection with
      T. gondii strain ME49 were investigated for 12 weeks postinfection (PI). The
      results showed that neuronal cell death, microglia infiltration and activation,
      inflammatory and anti-inflammatory cytokine expression, Stat1 phosphorylation,
      and microglia activation and inflammatory gene transcripts related to M1
      polarization in the brain were increased during the acute infection (AI) stage
      (within 6 weeks PI), suggesting that innate and cellular inflammatory response
      activation and neurodegeneration contributed to excessive inflammatory responses.
      However, these immune responses decreased during the chronic infection (CI) stage
      (over 6 weeks PI) with reductions in phosphorylated STAT1 (pSTAT1) and
      eosinophilic neurons. Notably, increases were observed in transcripts of T-cell
      exhaustion markers (TIM3, LAG3, KLRG1, etc.), suppressor of cytokines signaling 1
      protein (SOCS1), inhibitory checkpoint molecules (PD-1 and PD-L1), and Arg1 from
      the AI stage (3 weeks PI), implying active immune intervention under the immune
      environment of M1 polarization of microglia and increases in inflammatory
      cytokine levels. However, when BV-2 microglia were stimulated with T. gondii
      lysate antigens (strain RH or ME49) in vitro, nitrite production increased and
      urea production decreased. Furthermore, when BV-2 cells were infected by T.
      gondii tachyzoites (strain RH or ME49) in vitro, nitric oxide synthase and COX-2
      levels decreased, whereas Arg1 levels significantly increased. Moreover, Arg1
      expression was higher in ME49 infection than in RH infection, whereas nitrite
      production was lower in ME49 infection than in RH infection. Accordingly, these
      results strongly suggest that immune triggering of T. gondii antigens induces M1
      polarization and activation of microglia as well as increase NO production,
      whereas T. gondii infection induces the inhibition of harmful inflammatory
      responses, even with M1 polarization and activation of microglia and Th1
      inflammatory responses, suggesting a host-parasite relationship through immune
      regulation during CI. This is a characteristic of infection immunity in infection
      with T. gondii in the central nervous system, and SOCS1, a negative regulator of
      toxoplasmic encephalitis, may play a role in the increase in Arg1 levels to
      suppress NO production.

PMID- 29459869
TI  - Fcu Receptor Promotes the Survival and Activation of Marginal Zone B Cells and
      Protects Mice against Bacterial Sepsis.
AB  - The marginal zone B cells (MZB) are located at the interface between the
      circulation and lymphoid tissue and as a gatekeeper play important roles in both
      innate and adaptive immune responses. We have previously found that MZB are
      significantly reduced in mice deficient in the IgM Fc receptor (FcMUR) but how
      FcMUR regulates the development and function of MZB remains unknown. In this
      study, we found that both marginal zone precursor (MZP) and MZB were decreased in
      FcMUR-/- mice. The reduction of MZP and MZB was not due to impaired proliferation
      of these cells but rather due to their increased death. Further analysis revealed
      that FcMUR-/- MZB had reduced tonic BCR signal, as evidenced by their decreased
      levels of phosphorylated SYK and AKT relative to WT MZB. MZB in FcMUR-/- mice
      responded poorly to LPS in vivo when compared with MZB in WT mice. Consistent
      with the reduced proportion of MZB and their impaired response to LPS, antibody
      production against the type 1 T-independent Ag, NP-LPS, was significantly reduced
      in FcMUR-/- mice. Moreover, FcMUR-/- mice were highly susceptible to Citrobacter
      rodentium-induced sepsis. These results reveal a critical role for FcMUR in the
      survival and activation of MZB and in protection against acute bacterial
      infection.

PMID- 29459867
TI  - The Multirole of Liposomes in Therapy and Prevention of Infectious Diseases.
AB  - Liposomes are closed bilayer structures spontaneously formed by hydrated
      phospholipids that are widely used as efficient delivery systems for drugs or
      antigens, due to their capability to encapsulate bioactive hydrophilic,
      amphipathic, and lipophilic molecules into inner water phase or within lipid
      leaflets. The efficacy of liposomes as drug or antigen carriers has been improved
      in the last years to ameliorate pharmacokinetics and capacity to release their
      cargo in selected target organs or cells. Moreover, different formulations and
      variations in liposome composition have been often proposed to include
      immunostimulatory molecules, ligands for specific receptors, or stimuli
      responsive compounds. Intriguingly, independent research has unveiled the
      capacity of several phospholipids to play critical roles as intracellular
      messengers in modulating both innate and adaptive immune responses through
      various mechanisms, including (i) activation of different antimicrobial enzymatic
      pathways, (ii) driving the fusion-fission events between endosomes with direct
      consequences to phagosome maturation and/or to antigen presentation pathway, and
      (iii) modulation of the inflammatory response. These features can be exploited by
      including selected bioactive phospholipids in the bilayer scaffold of liposomes.
      This would represent an important step forward since drug or antigen carrying
      liposomes could be engineered to simultaneously activate different signal
      transduction pathways and target specific cells or tissues to induce antigen
      specific T and/or B cell response. This lipid-based host-directed strategy can
      provide a focused antimicrobial innate and adaptive immune response against
      specific pathogens and offer a novel prophylactic or therapeutic option against
      chronic, recurrent, or drug-resistant infections.

PMID- 29459870
TI  - Is the A-Chain the Engine That Drives the Diversity of C1q Functions? Revisiting
      Its Unique Structure.
AB  - The immunopathological functions associated with human C1q are still growing in
      terms of novelty, diversity, and pathologic relevance. It is, therefore, not
      surprising that C1q is being recognized as an important molecular bridge between
      innate and adaptive immunity. The secret of this functional diversity, in turn,
      resides in the elegant but complex structure of the C1q molecule, which is
      assembled from three distinct gene products: A, B, and C, each of which has
      evolved from a separate and unique ancestral gene template. The C1q molecule is
      made up of 6A, 6B, and 6C polypeptide chains, which are held together through
      strong covalent and non-covalent bonds to form the 18-chain, bouquet-of-flower
      like protein that we know today. The assembled C1q protein displays at least two
      distinct structural and functional regions: the collagen-like region (cC1q) and
      the globular head region (gC1q), each being capable of driving a diverse range of
      ligand- or receptor-mediated biological functions. What is most intriguing,
      however, is the observation that most of the functions appear to be predominantly
      driven by the A-chain of the molecule, which begs the question: what are the
      evolutionary modifications or rearrangements that singularly shaped the
      primordial A-chain gene to become a pluripotent and versatile component of the
      intact C1q molecule? Here, we revisit and discuss some of the known unique
      structural and functional features of the A-chain, which may have contributed to
      its versatility.

PMID- 29459871
TI  - Staphylococcal Protein A Is a Key Factor in Neutrophil Extracellular Traps
      Formation.
AB  - Staphylococcus aureus are strong inducers of neutrophil extracellular traps
      (NETs), a defense mechanism of neutrophils against pathogens. Our aim was to
      explore the role of Protein A in S. aureus-induced NETosis. We determined the
      Protein A production of four different S. aureus strains and found a direct
      relationship between the degree of NETosis induction and Protein A production:
      strains producing higher concentrations of Protein A evoke significantly more
      NETs. A S. aureus strain in which Protein A as well as a second binding protein
      for immunoglobulins (Sbi) have been knocked-out (DeltaSpA DeltaSbi) induced
      significantly less NETosis than the wild-type strain. NETosis induction by this
      knockout strain can be rescued by the addition of purified Protein A. Dead S.
      aureus did not induce NETosis. In conclusion, Protein A is a determinant for
      NETosis induction by S. aureus.

PMID- 29459872
TI  - The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide
      Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression
      in Mice.
AB  - Neurokinin (NK) signaling is involved in various inflammatory processes. A common
      manifestation of systemic inflammation is fever, which is usually induced in
      animal models with the administration of bacterial lipopolysaccharide (LPS). A
      role for the NK1 receptor was shown in LPS-induced fever, but the underlying
      mechanisms of how the NK1 receptor contributes to febrile response, especially in
      the early phase, have remained unknown. We administered LPS (120 ug/kg,
      intraperitoneally) to mice with the Tacr1 gene, i.e., the gene encoding the NK1
      receptor, either present (Tacr1+/+ ) or absent (Tacr1-/- ) and measured their
      thermoregulatory responses, serum cytokine levels, tissue cyclooxygenase-2 (COX
      2) expression, and prostaglandin (PG) E2 concentration. We found that the LPS
      induced febrile response was attenuated in Tacr1-/- compared to their Tacr1+/+
      littermates starting from 40 min postinfusion. The febrigenic effect of
      intracerebroventricularly administered PGE2 was not suppressed in the Tacr1-/-
      mice. Serum concentration of pyrogenic cytokines did not differ between Tacr1-/-
      and Tacr1+/+ at 40 min post-LPS infusion. Administration of LPS resulted in
      amplification of COX-2 mRNA expression in the lungs, liver, and brain of the
      mice, which was statistically indistinguishable between the genotypes. In
      contrast, the LPS-induced augmentation of COX-2 protein expression was attenuated
      in the lungs and tended to be suppressed in the liver of Tacr1-/- mice compared
      with Tacr1+/+ mice. The Tacr1+/+ mice responded to LPS with a significant surge
      of PGE2 production in the lungs, whereas Tacr1-/- mice did not. In conclusion,
      the NK1 receptor is necessary for normal fever genesis. Our results suggest that
      the NK1 receptor contributes to the early phase of LPS-induced fever by enhancing
      COX-2 protein expression in the periphery. These findings advance the
      understanding of the crosstalk between NK signaling and the "cytokine-COX-2
      prostaglandin E2" axis in systemic inflammation, thereby open up the
      possibilities for new therapeutic approaches.

PMID- 29459873
TI  - Integrase Defective Lentiviral Vector as a Vaccine Platform for Delivering
      Influenza Antigens.
AB  - Viral vectors represent an attractive technology for vaccine delivery. We
      exploited the integrase defective lentiviral vector (IDLV) as a platform for
      delivering relevant antigens within the context of the ADITEC collaborative
      research program. In particular, Influenza virus hemagglutinin (HA) and
      nucleoprotein (NP) were delivered by IDLVs while H1N1 A/California/7/2009 subunit
      vaccine (HAp) with or without adjuvant was used to compare the immune response in
      a murine model of immunization. In order to maximize the antibody response
      against HA, both IDLVs were also pseudotyped with HA (IDLV-HA/HA and IDLV-NP/HA,
      respectively). Groups of CB6F1 mice were immunized intramuscularly with a single
      dose of IDLV-NP/HA, IDLV-HA/HA, HAp alone, or with HAp together with the systemic
      adjuvant MF59. Six months after the vaccine prime all groups were boosted with
      HAp alone. Cellular and antibody responses to influenza antigens were measured at
      different time points after the immunizations. Mice immunized with HA-pseudotyped
      IDLVs showed similar levels of anti-H1N1 IgG over time, evaluated by ELISA, which
      were comparable to those induced by HAp + MF59 vaccination, but significantly
      higher than those induced by HAp alone. The boost with HAp alone induced an
      increase of antibodies in all groups, and the responses were maintained at higher
      levels up to 18 weeks post-boost. The antibody response was functional and
      persistent overtime, capable of neutralizing virus infectivity, as evaluated by
      hemagglutination inhibition and microneutralization assays. Moreover, since
      neuraminidase (NA)-expressing plasmid was included during IDLV preparation,
      immunization with IDLV-NP/HA and IDLV-HA/HA also induced functional anti-NA
      antibodies, evaluated by enzyme-linked lectin assay. IFNgamma-ELISPOT showed
      evidence of HA-specific response in IDLV-HA/HA immunized animals and persistent
      NP-specific CD8+ T cell response in IDLV-NP/HA immunized mice. Taken together our
      results indicate that IDLV can be harnessed for producing a vaccine able to
      induce a comprehensive immune response, including functional antibodies directed
      toward HA and NA proteins present on the vector particles in addition to a
      functional T cell response directed to the protein transcribed from the vector.

PMID- 29459875
TI  - Decrease in the Photosynthetic Performance of Temperate Grassland Species Does
      Not Lead to a Decline in the Gross Primary Production of the Ecosystem.
AB  - Plants, under stressful conditions, can proceed to photosynthetic adjustments in
      order to acclimatize and alleviate the detrimental impacts on the photosynthetic
      apparatus. However, it is currently unclear how adjustment of photosynthetic
      processes under environmental constraints by plants influences CO2 gas exchange
      at the ecosystem-scale. Over a 2-year period, photosynthetic performance of a
      temperate grassland ecosystem was characterized by conducting frequent
      chlorophyll fluorescence (ChlF) measurements on three primary grassland species
      (Lolium perenne L., Taraxacum sp., and Trifolium repens L.). Ecosystem
      photosynthetic performance was estimated from measurements performed on the three
      dominant grassland species weighed based on their relative abundance. In
      addition, monitoring CO2 fluxes was performed by eddy covariance. The highest
      decrease in photosynthetic performance was detected in summer, when environmental
      constraints were combined. Dicot species (Taraxacum sp. and T. repens) presented
      the strongest capacity to up-regulate PSI and exhibited the highest electron
      transport efficiency under stressful environmental conditions compared with L.
      perenne. The decline in ecosystem photosynthetic performance did not lead to a
      reduction in gross primary productivity, likely because increased light energy
      was available under these conditions. The carbon amounts fixed at light
      saturation were not influenced by alterations in photosynthetic processes,
      suggesting photosynthesis was not impaired. Decreased photosynthetic performance
      was associated with high respiration flux, but both were influenced by
      temperature. Our study revealed variation in photosynthetic performance of a
      grassland ecosystem responded to environmental constraints, but alterations in
      photosynthetic processes appeared to exhibit a negligible influence on ecosystem
      CO2 fluxes.

PMID- 29459876
TI  - Mapping Late Leaf Spot Resistance in Peanut (Arachis hypogaea) Using QTL-seq
      Reveals Markers for Marker-Assisted Selection.
AB  - Late leaf spot (LLS; Cercosporidium personatum) is a major fungal disease of
      cultivated peanut (Arachis hypogaea). A recombinant inbred line population
      segregating for quantitative field resistance was used to identify quantitative
      trait loci (QTL) using QTL-seq. High rates of false positive SNP calls using
      established methods in this allotetraploid crop obscured significant QTLs. To
      resolve this problem, robust parental SNPs were first identified using polyploid
      specific SNP identification pipelines, leading to discovery of significant QTLs
      for LLS resistance. These QTLs were confirmed over 4 years of field data.
      Selection with markers linked to these QTLs resulted in a significant increase in
      resistance, showing that these markers can be immediately applied in breeding
      programs. This study demonstrates that QTL-seq can be used to rapidly identify
      QTLs controlling highly quantitative traits in polyploid crops with complex
      genomes. Markers identified can then be deployed in breeding programs, increasing
      the efficiency of selection using molecular tools. Key Message: Field resistance
      to late leaf spot is a quantitative trait controlled by many QTLs. Using
      polyploid-specific methods, QTL-seq is faster and more cost effective than QTL
      mapping.

PMID- 29459874
TI  - Traversing the Links between Heavy Metal Stress and Plant Signaling.
AB  - Plants confront multifarious environmental stresses widely divided into abiotic
      and biotic stresses, of which heavy metal stress represents one of the most
      damaging abiotic stresses. Heavy metals cause toxicity by targeting crucial
      molecules and vital processes in the plant cell. One of the approaches by which
      heavy metals act in plants is by over production of reactive oxygen species (ROS)
      either directly or indirectly. Plants act against such overdose of metal in the
      environment by boosting the defense responses like metal chelation, sequestration
      into vacuole, regulation of metal intake by transporters, and intensification of
      antioxidative mechanisms. This response shown by plants is the result of
      intricate signaling networks functioning in the cell in order to transmit the
      extracellular stimuli into an intracellular response. The crucial signaling
      components involved are calcium signaling, hormone signaling, and mitogen
      activated protein kinase (MAPK) signaling that are discussed in this review.
      Apart from signaling components other regulators like microRNAs and transcription
      factors also have a major contribution in regulating heavy metal stress. This
      review demonstrates the key role of MAPKs in synchronously controlling the other
      signaling components and regulators in metal stress. Further, attempts have been
      made to focus on metal transporters and chelators that are regulated by MAPK
      signaling.

PMID- 29459877
TI  - Simultaneous Transfer of Leaf Rust and Powdery Mildew Resistance Genes from
      Hexaploid Triticale Cultivar Sorento into Bread Wheat.
AB  - Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici, and wheat leaf
      rust, caused by Puccinia triticina Eriks, are two important diseases that
      severely threaten wheat production. Sorento, a hexaploid triticale cultivar from
      Poland, shows high resistance to the wheat powdery mildew isolate E09 and the
      leaf rust isolate PHT in Beijing, China. To introduce resistance genes into
      common wheat, Sorento was crossed with wheat line Xuezao, which is susceptible to
      both diseases, and the F1 hybrids were then backcrossed with Xuezao as the
      recurrent male parent. By marker analysis, we demonstrate that the long arm of
      the 2R (2RL) chromosome confers resistance to both the leaf rust and powdery
      mildew isolates at adult-plant and seedling stages, while the long arm of 4R
      (4RL) confers resistance only to powdery mildew at both stages. The chromosomal
      composition of BC2F3 plants containing 2R or 2RL and 4R or 4RL in the form of
      substitution and translocation were confirmed by GISH (genomic in situ
      hybridization) and FISH (fluorescence in situ hybridization). Monosomic and
      disomic substitutions of a wheat chromosome with chromosome 2R or 4R, as well as
      one 4RS-4DL/4DS-4RL reciprocal translocation homozigote and one 2RL-1DL
      translocation hemizigote, were recovered. Such germplasms are of great value in
      wheat improvement.

PMID- 29459878
TI  - Bemisia tabaci MED Population Density as Affected by Rootstock-Modified Leaf
      Anatomy and Amino Acid Profiles in Hydroponically Grown Tomato.
AB  - Bemisia tabaci is one of the most devastating pests in tomato greenhouse
      production. Insecticide resistance management for B. tabaci requires a novel
      approach that maximizes non-chemical methods for pest control. The aim of this
      study was to test the effects of rootstocks on B. tabaci populations in
      hydroponically grown tomato plants. In order to contribute to the better
      understanding of the mechanisms defining the attractiveness of plant to the
      aerial pest, the effects of rootstocks on leaf anatomy and the amino acid
      composition of phloem sap were assessed. A two-factorial experimental design was
      adopted using cultivars (rootstock cultivars and Clarabella) grown as either non
      grafted or grafted with cultivar Clarabella as a scion. The rootstock cultivars
      included Arnold, Buffon, Emperador, and Maxifort. A reduction in B. tabaci
      density was observed using all rootstock cultivars. The number of adult
      individuals per leaf was 2.7-5.4 times lower on rootstock cultivars than on
      Clarabella. The number of large nymphs per square centimeter was at least 24%
      higher on non-grafted Clarabella compared with all other treatments. The leaf
      lamina thickness and mesophyll thickness were lower in self-grafted Clarabella
      than in non-grafted or in one grafted on rootstock cultivars; however, the extent
      of this reduction depended on the rootstock. The leaves with thinner laminae were
      generally less attractive to B. tabaci. Eighteen amino acids were detected in the
      exudates of phloem sap. In all treatments, the most abundant amino acid was gamma
      aminobutyric acid (GABA), followed by proline, serine, alanine, and histidine.
      The scion cultivar Clarabella was the most attractive to B. tabaci and had a
      higher content of leucine than did rootstock cultivars, and a higher content of
      lysine compared to Buffon and Maxifort. The features modified by rootstock such
      are changes in leaf anatomy can affect the attractiveness of plants to B. tabaci.
      Thus, the grafting of tomato could constitute a valuable tool in an integrated
      management strategy against this aerial pest.

PMID- 29459879
TI  - Cold-Induced Male Meiotic Restitution in Arabidopsis thaliana Is Not Mediated by
      GA-DELLA Signaling.
AB  - Short periods of cold stress induce male meiotic restitution and diploid pollen
      formation in Arabidopsis thaliana by specifically interfering with male meiotic
      cytokinesis. Similar alterations in male meiotic cell division and gametophytic
      ploidy stability occur when gibberellic acid (GA) signaling is perturbed in
      developing anthers. In this study, we found that exogenous application of GA
      primarily induces second division restitution (SDR)-type pollen in Arabidopsis,
      similar to what cold does. Driven by the close similarity in cellular defects, we
      tested the hypothesis that cold-induced meiotic restitution is mediated by GA
      DELLA signaling. Using a combination of chemical, genetic and cytological
      approaches, however, we found that both exogenously and endogenously altered GA
      signaling do not affect the cold sensitivity of male meiotic cytokinesis.
      Moreover, in vivo localization study using a GFP-tagged version of RGA protein
      revealed that cold does not affect the expression pattern and abundance of DELLA
      in Arabidopsis anthers at tetrad stage. Expression study found that transcript of
      RGA appears enhanced in cold-stressed young flower buds. Since our previous work
      demonstrated that loss of function of DELLA causes irregular male meiotic
      cytokinesis, we here conclude that cold-induced meiotic restitution is not
      mediated by DELLA-dependent GA signaling.

PMID- 29459881
TI  - Fatty Acid and Associated Gene Expression Analyses of Three Tree Peony Species
      Reveal Key Genes for alpha-Linolenic Acid Synthesis in Seeds.
AB  - The increasing demand for healthy edible oil has generated the need to identify
      promising oil crops. Tree peony (Paeonia section Moutan DC.) is a woody oil crop
      with alpha-linolenic acid (ALA) contributing for 45% of the total fatty acid (FA)
      content in seeds. Molecular and genetic differences that contribute to varied FA
      content and composition among the wild peony species are, however, poorly
      understood. Analyses of FA content and composition during seed development in
      three tree peony species (Paeonia rockii, P. potaninii, and P. lutea) showed
      varied FA content among them with highest in P. rockii, followed by P. potaninii,
      and P. lutea. Total FA content among these species increased with seed
      development and reached its maximum in its final stage. Seed FA composition
      analysis of the three species also revealed that ALA (C18:3) was the most
      abundant, followed by oleic (C18:1) and linoleic (C18:2) acids. Additionally,
      quantitative real-time RT-PCR analyses of 10 key seed oil synthesis genes in the
      three tree peony species revealed that FAD3, FAD2, beta-PDHC, LPAAT, and Oleosin
      gene expression levels positively correlate with total FA content and rate of
      accumulation. Specifically, the abundance of FAD3 transcripts in P. rockii
      compared with P. potaninii, and P. lutea suggests that FAD3 might play an
      important role in synthesis of ALA via phosphatidylcholine-derived pathway.
      Overall, comparative analyses of FA content and composition in three different
      peony species revealed a correlation between efficient lipid accumulation and
      lipid gene expression during seed development. Further characterization and
      metabolic engineering of these key genes from peonies will allow for subsequent
      improvement of tree peony oil quality and production.

PMID- 29459880
TI  - Molecular Phylogeny and Dating of Forsythieae (Oleaceae) Provide Insight into the
      Miocene History of Eurasian Temperate Shrubs.
AB  - Tribe Forsythieae (Oleaceae), containing two genera (Abeliophyllum and Forsythia)
      and 13 species, is economically important plants used as ornamentals and in
      traditional medicine. This tribe species occur primarily in mountainous regions
      of Eurasia with the highest species diversity in East Asia. Here, we examine 11
      complete chloroplast genome and nuclear cycloidea2 (cyc2) DNA sequences of 10
      Forsythia species and Abeliophyllum distichum using Illumina platform to provide
      the phylogeny and biogeographic history of the tribe. The chloroplast genomes of
      the 11 Forsythieae species are highly conserved, except for a deletion of about
      400 bp in the accD-psaI region detected only in Abeliophyllum. Within Forsythieae
      species, analysis of repetitive sequences revealed a total of 51 repeats
      comprising 26 forward repeats, 22 palindromic repeats, and 3 reverse repeats. Of
      those, 19 repeats were common and 32 were unique to one or more Forsythieae
      species. Our phylogenetic analyses supported the monophyly of Forsythia and its
      sister group is Abeliophyllum using the concatenated dataset of 78 chloroplast
      genes. Within Forsythia, Forsythia likiangensis and F. giraldiana were basal
      lineages followed by F. europaea; the three species are characterized by minutely
      serrate or entire leaf margins. The remaining species, which are distributed in
      East Asia, formed two major clades. One clade included F. ovata, F. velutina, and
      F. japonica; they are morphologically supported by broadly ovate leaves. Another
      clade of F. suspensa, F. saxatilis, F. viridissima, and F. koreana characterized
      by lanceolate leaves (except F. suspensa which have broad ovate leaves). Although
      cyc2 phylogeny is largely congruent to chloroplast genome phylogeny, we find the
      discordance between two phylogenies in the position of F. ovata suggesting that
      introgression of the chloroplast genome from one species into the nuclear
      background of another by interspecific hybridization in East Asian Forsythia
      species. Molecular dating and biogeographic reconstructions suggest an origin of
      the Forsythieae species in East China in the Miocene. Distribution patterns in
      Forsythia indicated that the species were radially differentiated from East
      China, and the speciation of the European F. europaea was the result of both
      vicariance and dispersal in the late Miocene to Pliocene.

PMID- 29459882
TI  - Identification of a New Mullet Species Complex Based on an Integrative Molecular
      and Cytogenetic Investigation of Mugil hospes (Mugilidae: Mugiliformes).
AB  - Mullets are very common fishes included in the family Mugilidae, (Mugiliformes),
      which are characterized by both a remarkably uniform external morphology and
      internal anatomy. Recently, within this family, different species complexes were
      molecularly identified within Mugil, a genus which is characterized by lineages
      that sometimes show very different karyotypes. Here we report the results of
      cytogenetic and molecular analyses conducted on Mugil hospes, commonly known as
      the hospe mullet, from Ecuador. The study aims to verify whether the original
      described species from the Pacific Ocean corresponds to that identified in the
      Atlantic Ocean, and to identify species-specific chromosome markers that can add
      new comparative data about Mugilidae karyotype evolution. The karyotype of M.
      hospes from Ecuador is composed of 48 acrocentric chromosomes and shows two
      active nucleolar organizer regions (NORs). In situ hybridization, using different
      types of repetitive sequences (rDNAs, U1 snDNA, telomeric repeats) as probes,
      identified species-specific chromosome markers that have been compared with those
      of other species of the genus Mugil. Cytochrome c oxidase subunit I (COI)
      sequence analysis shows only 92-93% similarity with sequences previously
      deposited under this species name in GenBank, all of which were from the Atlantic
      Ocean. Phylogenetic reconstructions indicate the presence of three well-supported
      hospe mullet lineages whose molecular divergence is compatible with the presence
      of distinct species. Indeed, the first lineage includes samples from Ecuador,
      whereas the other two lineages include the Atlantic samples and correspond to M.
      brevirostris from Brazil and Mugil sp. R from Belize/Venezuela. Results here
      provided reiterate the pivotal importance of an integrative molecular and
      cytogenetic approach in the reconstruction of the relationships within Mugilidae.

PMID- 29459884
TI  - Ecological Networks and Urban Crime: The Structure of Shared Routine Activity
      Locations and Neighborhood-Level Informal Control Capacity.
AB  - Drawing on Jacobs (1961), we hypothesize that public contact among neighborhood
      residents while engaged in day-to-day routines, captured by the aggregate network
      structure of shared local exposure, is consequential for crime. Neighborhoods in
      which residents come into contact more extensively in the course of conventional
      routines will exhibit higher levels of public familiarity, trust, and collective
      efficacy with implications for the informal social control of crime. We employ
      the concept of ecological ("eco-") networks - networks linking households within
      neighborhoods through shared activity locations - to formalize the notion of
      overlapping routines. Using micro-simulations of household travel patterns to
      construct census tract-level eco-networks for Columbus, OH, we examine the
      hypothesis that eco-network intensity (the probability that households tied
      through one location in a neighborhood eco-network will also be tied through
      another visited location) is negatively associated with tract-level crime rates
      (N=192). Fitted spatial autoregressive models offer evidence that neighborhoods
      with higher intensity eco-networks exhibit lower levels of violent and property
      crime. In contrast, a higher prevalence of non-resident visitors to a given tract
      is positively associated with property crime. These analyses hold the potential
      to enrich insight into the ecological processes that shape variation in
      neighborhood crime.

PMID- 29459883
TI  - Transcriptomic and Proteomic Profiling Revealed High Proportions of Odorant
      Binding and Antimicrobial Defense Proteins in Olfactory Tissues of the House
      Mouse.
AB  - Mammalian olfaction depends on chemosensory neurons of the main olfactory
      epithelia (MOE), and/or of the accessory olfactory epithelia in the vomeronasal
      organ (VNO). Thus, we have generated the VNO and MOE transcriptomes and the nasal
      cavity proteome of the house mouse, Mus musculus musculus. Both transcriptomes
      had low levels of sexual dimorphisms, while the soluble proteome of the nasal
      cavity revealed high levels of sexual dimorphism similar to that previously
      reported in tears and saliva. Due to low levels of sexual dimorphism in the
      olfactory receptors in MOE and VNO, the sex-specific sensing seems less likely to
      be dependent on receptor repertoires. However, olfaction may also depend on a
      continuous removal of background compounds from the sites of detection. Odorant
      binding proteins (OBPs) are thought to be involved in this process and in our
      study Obp transcripts were most expressed along other lipocalins (e.g., Lcn13,
      Lcn14) and antimicrobial proteins. At the level of proteome, OBPs were highly
      abundant with only few being sexually dimorphic. We have, however, detected the
      major urinary proteins MUP4 and MUP5 in males and females and the male-biased
      central/group-B MUPs that were thought to be abundant mainly in the urine. The
      exocrine gland-secreted peptides ESP1 and ESP22 were male-biased but not male
      specific in the nose. For the first time, we demonstrate that the expression of
      nasal lipocalins correlates with antimicrobial proteins thus suggesting that
      their individual variation may be linked to evolvable mechanisms that regulate
      natural microbiota and pathogens that regularly enter the body along the 'eyes
      nose-oral cavity' axis.

PMID- 29459885
TI  - Platelet-Activating Factor Receptor Ligands Protect Tumor Cells from Radiation
      Induced Cell Death.
AB  - Irradiation generates oxidized phospholipids that activate platelet-activating
      factor receptor (PAFR) associated with pro-tumorigenic effects. Here, we
      investigated the involvement of PAFR in tumor cell survival after irradiation.
      Cervical cancer samples presented higher levels of PAF-receptor gene (PTAFR) when
      compared with normal cervical tissue. In cervical cancer patients submitted to
      radiotherapy (RT), the expression of PTAFR was significantly increased. Cervical
      cancer-derived cell lines (C33, SiHa, and HeLa) and squamous carcinoma cell lines
      (SCC90 and SCC78) express higher levels of PAFR mRNA and protein than
      immortalized keratinocytes. Gamma radiation increased PAFR expression and induced
      PAFR ligands and prostaglandin E2 (PGE2) in these tumor cells. The blocking of
      PAFR with the antagonist CV3938 before irradiation inhibited PGE2 and increased
      tumor cells death. Similarly, human carcinoma cells transfected with PAFR (KBP)
      were more resistant to radiation compared to those lacking the receptor (KBM).
      PGE2 production by irradiated KBP cells was also inhibited by CV3988. These
      results show that irradiation of carcinoma cells generates PAFR ligands that
      protect tumor cells from death and suggests that the combination of RT with a
      PAFR antagonist could be a promising strategy for cancer treatment.

PMID- 29459886
TI  - DNA Damage, Repair, and Cancer Metabolism.
AB  - Although there has been a renewed interest in the field of cancer metabolism in
      the last decade, the link between metabolism and DNA damage/DNA repair in cancer
      has yet to be appreciably explored. In this review, we examine the evidence
      connecting DNA damage and repair mechanisms with cell metabolism through three
      principal links. (1) Regulation of methyl- and acetyl-group donors through
      different metabolic pathways can impact DNA folding and remodeling, an essential
      part of accurate double strand break repair. (2) Glutamine, aspartate, and other
      nutrients are essential for de novo nucleotide synthesis, which dictates the
      availability of the nucleotide pool, and thereby influences DNA repair and
      replication. (3) Reactive oxygen species, which can increase oxidative DNA damage
      and hence the load of the DNA-repair machinery, are regulated through different
      metabolic pathways. Interestingly, while metabolism affects DNA repair, DNA
      damage can also induce metabolic rewiring. Activation of the DNA damage response
      (DDR) triggers an increase in nucleotide synthesis and anabolic glucose
      metabolism, while also reducing glutamine anaplerosis. Furthermore, mutations in
      genes involved in the DDR and DNA repair also lead to metabolic rewiring. Links
      between cancer metabolism and DNA damage/DNA repair are increasingly apparent,
      yielding opportunities to investigate the mechanistic basis behind potential
      metabolic vulnerabilities of a substantial fraction of tumors.

PMID- 29459887
TI  - Role of BRCA Mutations in the Modulation of Response to Platinum Therapy.
AB  - Recent years have seen cancer emerge as one of the leading cause of mortality
      worldwide with breast cancer being the second most common cause of death among
      women. Individuals harboring BRCA mutations are at a higher risk of developing
      breast and/or ovarian cancers. This risk is much greater in the presence of
      germline mutations. BRCA1 and BRCA2 play crucial role in the DNA damage response
      and repair pathway, a function that is critical in preserving the integrity of
      the genome. Mutations that interfere with normal cellular function of BRCA not
      only lead to onset and progression of cancer but also modulate therapy outcome of
      treatment with platinum drugs. In this review, we discuss the structural and
      functional impact of some of the prevalent BRCA mutations in breast and ovarian
      cancers and their role in platinum therapy response. Understanding the response
      of platinum drugs in the context of BRCA mutations may contribute toward
      developing better therapeutics that can improve survival and quality of life of
      patients.

PMID- 29459888
TI  - Genetic Separation of Listeria monocytogenes Causing Central Nervous System
      Infections in Animals.
AB  - Listeria monocytogenes is a foodborne pathogen that causes abortion, septicemia,
      gastroenteritis and central nervous system (CNS) infections in ruminants and
      humans. L. monocytogenes strains mainly belong to two distinct phylogenetic
      groups, named lineages I and II. In general, clinical cases in humans and
      animals, in particular CNS infections, are caused by lineage I strains, while
      most of the environmental and food strains belong to lineage II. Little is known
      about why lineage I is more virulent than lineage II, even though various
      molecular factors and mechanisms associated with pathogenesis are known. In this
      study, we have used a variety of whole genome sequence analyses and comparative
      genomic tools in order to find characteristics that distinguish lineage I from
      lineage II strains and CNS infection strains from non-CNS strains. We analyzed
      225 strains and identified single nucleotide variants between lineages I and II,
      as well as differences in the gene content. Using a novel approach based on Reads
      Per Kilobase per Million Mapped (RPKM), we identified 167 genes predominantly
      absent in lineage II but present in lineage I. These genes are mostly encoding
      for membrane-associated proteins. Additionally, we found 77 genes that are
      largely absent in the non-CNS associated strains, while 39 genes are especially
      lacking in our defined "non-clinical" group. Based on the RPKM analysis and the
      metadata linked to the L. monocytogenes strains, we identified 6 genes
      potentially associated with CNS cases, which include a transcriptional regulator,
      an ABC transporter and a non-coding RNA. Although there is not a clear separation
      between pathogenic and non-pathogenic strains based on phylogenetic lineages, the
      presence of the genes identified in our study reveals potential pathogenesis
      traits in ruminant L. monocytogenes strains. Ultimately, the differences that we
      have found in our study will help steer future studies in understanding the
      virulence mechanisms of the most pathogenic L. monocytogenes strains.

PMID- 29459889
TI  - Case Report: A Child with Gross Hematuria and the Importance of Travel History.
AB  - We report a case of a 5-year-old girl who presented with a 3-month-long history
      of gross hematuria. She underwent an extensive laboratory workup (including an
      automated urine microscopy) and a kidney biopsy, all of which were within normal
      limits. While being prepared for a cystoscopy and more advanced imaging of the
      urinary tract, the family mentioned history of travel to a schistosomiasis
      endemic area prompting a more thorough ova and parasite examination of the urine.
      Urine microscopy confirmed the diagnosis of Schistosoma hematobium.

PMID- 29459890
TI  - Promoting Local Ownership: Lessons Learned from Process of Transitioning Clinical
      Mentoring of HIV Care and Treatment in Ethiopia.
AB  - Introduction: Focus on improving access and quality of HIV care and treatment
      gained acceptance in Ethiopia through the work of the International Training and
      Education Center for Health. The initiative deployed mobile field-based teams and
      capacity building teams to mentor health care providers on clinical services and
      program delivery in three regions, namely Tigray, Amhara, and Afar. Transitioning
      of the clinical mentoring program (CMP) began in 2012 through capacity building
      and transfer of skills and knowledge to local health care providers and
      management. Objective: The initiative explored the process of transitioning a CMP
      on HIV care and treatment to local ownership and documented key lessons learned.
      Methods: A mixed qualitative design was used employing focus group discussions,
      individual in-depth interviews, and review of secondary data. The participants
      included regional focal persons, mentors, mentees, multidisciplinary team
      members, and International Training and Education Center for Health (I-TECH)
      staff. Three facilities were selected in each region. Data were collected by
      trained research assistants using customized guides for interviews and with data
      extraction format. The interviews were recorded and fully transcribed. Open Code
      software was used for coding and categorizing the data. Results: A total of 16
      focus group discussions and 20 individual in-depth interviews were conducted. The
      critical processes for transitioning a project were: establishment of a mentoring
      transition task force, development of a roadmap to define steps and directions
      for implementing the transition, and signing of a memorandum of understanding
      (MOU) between the respective regional health bureaus and I-TECH Ethiopia to
      formalize the transition. The elements of implementation included mentorship and
      capacity building, joint mentoring, supportive supervision, review meetings, and
      independent mentoring supported by facility-based mechanisms: multidisciplinary
      team meetings, case-based discussions, and catchment area meetings. Conclusion:
      The process of transitioning the CMP to local ownership involved signing an MOU,
      training of mentors, and building capacity of mentoring in each region. The
      experience shed light on how to transition donor-supported work to local country
      ownership, with key lessons related to strengthening the structures of regional
      health bureaus, and other facilities addressing critical issues and ensuring
      continuity of the facility-based activities.

PMID- 29459891
TI  - Evaluating the Sporicidal Activity of Disinfectants against Clostridium difficile
      and Bacillus amyloliquefaciens Spores by Using the Improved Methods Based on ASTM
      E2197-11.
AB  - Spore-forming pathogenic bacteria, such as Clostridium difficile, are associated
      with nosocomial infection, leading to the increased use of sporicidal
      disinfectants, which impacts socioeconomic costs. However, C. difficile can be
      prevented using microorganisms such as Bacillus amyloliquefaciens, a prophylactic
      agent that has been proven to be effective against it in recent tests or it can
      be controlled by sporicidal disinfectants. These disinfectants against spores
      should be evaluated according to a known and recommended standard. Unfortunately,
      some newly manufactured disinfectants like Bioxy products have not yet been
      tested. ASTM E2197-11 is a standard test that uses stainless steel disks (1 cm in
      diameter) as carriers, and the performance of the test formulation is calculated
      by comparing the number of viable test organisms to that on the control carriers.
      Surface tests are preferable for evaluating disinfectants with sporicidal effects
      on hard surfaces. This study applies improved methods, based on the ASTM E2197-11
      standard, for evaluating and comparing the sporicidal efficacies of several
      disinfectants against spores of C. difficile and B. amyloliquefaciens, which are
      used as the test organisms. With the improved method, all spores were recovered
      through vortexing and membrane filtration. The results show that chlorine-based
      products are effective in 5 min and Bioxy products at 5% w/v are effective in 10
      min. Although Bioxy products may take longer to prove their effectiveness, their
      non-harmful effects to hospital surfaces and people have been well established in
      the literature.

PMID- 29459892
TI  - Mechanisms of Mitotic Kinase Regulation: A Structural Perspective.
AB  - Protein kinases are major regulators of mitosis, with over 30% of the mitotic
      proteome phosphorylated on serines, threonines and tyrosines. The human genome
      encodes for 518 kinases that have a structurally conserved catalytic domain and
      includes about a dozen of cell division specific ones. Yet each kinase has unique
      structural features that allow their distinct substrate recognition and modes of
      regulation. These unique regulatory features determine their accurate spatio
      temporal activation critical for correct progression through mitosis and are
      exploited for therapeutic purposes. In this review, we will discuss the
      principles of mitotic kinase activation and the structural determinants that
      underlie functional specificity.

PMID- 29459893
TI  - Biobehavioral Insights into Adaptive Behavior in Complex and Dynamic Operational
      Settings: Lessons learned from the Soldier Performance and Effective, Adaptable
      Response Task.
AB  - The purpose of this study was to explore the biobehavioral correlates of adaptive
      behavior in the context of a standardized laboratory-based mission-relevant
      challenge [the Soldier Performance and Effective, Adaptable Response (SPEAR)
      task]. Participants were 26 healthy male volunteers (M = 34.85 years, SD = 4.12)
      with active military duty and leadership experience within the last 5 years
      (i.e., multiple leadership positions, operational deployments in combat,
      interactions with civilians and partner nation forces on the battlefield,
      experience making decisions under fire). The SPEAR task simultaneously engages
      perception, cognition, and action aspects of human performance demands similar to
      those encountered in the operational setting. Participants must engage with
      military-relevant text, visual, and auditory stimuli, interpret new information,
      and retain the commander's intent in working memory to create a new plan of
      action for mission success. Time-domain measures of heart period and respiratory
      sinus arrhythmia (RSA) were quantified, and saliva was sampled [later assayed for
      cortisol and alpha-amylase (sAA)] before-, during-, and post-SPEAR. Results
      revealed a predictable pattern of withdraw and recovery of the cardiac vagal tone
      during repeated presentation of battlefield challenges. Recovery of vagal
      inhibition following executive function challenge was strongly linked to better
      task-related performance. Rate of RSA recovery was also associated with better
      recall of the commander's intent. Decreasing magnitude in the skin conductance
      response prior to the task was positively associated with better overall task
      related performance. Lower levels of RSA were observed in participants who
      reported higher rates of combat deployments, and reduced RSA flexibility was
      associated with higher rates of casualty exposure. Greater RSA flexibility during
      SPEAR was associated with greater self-reported resilience. There was no
      consistent pattern of task-related change in cortisol or sAA. We conclude that
      individual differences in psychophysiological reactivity and regulation in
      response to an ecologically valid, military-relevant task are associated with
      performance-related adaptive behavior in this standardized operational setting.
      The implications for modern day warfare, where advancing our understanding of the
      nature of individual differences in adaptive problem solving is critical to
      mission success, fitness for duty, and other occupational health-related
      outcomes, are discussed.

PMID- 29459894
TI  - Idiopathic Pulmonary Fibrosis: Aging, Mitochondrial Dysfunction, and Cellular
      Bioenergetics.
AB  - At present, the etiology of idiopathic pulmonary fibrosis (IPF) remains elusive.
      Over the past two decades, however, researchers have identified and described the
      underlying processes that result in metabolic dysregulation, metabolic
      reprogramming, and mitochondrial dysfunction observed in the cells of IPF lungs.
      Metabolic changes and mitochondrial dysfunction in IPF include decreased
      efficiency of electron transport chain function with increasing production of
      reactive oxygen species, decreased mitochondrial biogenesis, and impaired
      mitochondrial macroautophagy, a key pathway for the removal of dysfunctional
      mitochondria. Metabolic changes in IPF have potential impact on lung cell
      function, differentiation, and activation of fibrotic responses. These
      alterations result in activation of TGF-beta and predispose to the development of
      pulmonary fibrosis. IPF is a disease of the aged, and many of these same
      bioenergetic changes are present to a lesser extent with normal aging, raising
      the possibility that these anticipated alterations in metabolic processes play
      important roles in creating susceptibility to the development of IPF. This review
      explores what is known regarding the cellular metabolic and mitochondrial changes
      that are found in IPF, and examines this body of literature to identify future
      research direction and potential points of intervention in the pathogenesis of
      IPF.

PMID- 29459895
TI  - Enhanced Recovery in Thoracic Surgery: A Review.
AB  - The main goal of enhanced recovery program after thoracic surgery is to minimize
      stress response, reduce postoperative pulmonary complications, and improve
      patient outcome, which will in addition decrease hospital stay and reduce
      hospital costs. As minimally invasive technique, video-assisted thoracoscopic
      surgery represents an important element of enhanced recovery program in thoracic
      surgery. Anesthetic management during preoperative, intraoperative and
      postoperative period is essential for the enhanced recovery. In the era of
      enhanced recovery protocols, non-intubated thoracoscopic procedures present a
      step forward. This article focuses on the key elements of the enhanced recovery
      program in thoracic surgery. Having reviewed recent literature, the authors
      highlight potential procedures and techniques that might be incorporated into the
      program.

PMID- 29459896
TI  - Redox Status, Procoagulant Activity, and Metabolome of Fresh Frozen Plasma in
      Glucose 6-Phosphate Dehydrogenase Deficiency.
AB  - Objective: Transfusion of fresh frozen plasma (FFP) helps in maintaining the
      coagulation parameters in patients with acquired multiple coagulation factor
      deficiencies and severe bleeding. However, along with coagulation factors and
      procoagulant extracellular vesicles (EVs), numerous bioactive and probably donor
      related factors (metabolites, oxidized components, etc.) are also carried to the
      recipient. The X-linked glucose 6-phosphate dehydrogenase deficiency (G6PD-), the
      most common human enzyme genetic defect, mainly affects males. By undermining the
      redox metabolism, the G6PD- cells are susceptible to the deleterious effects of
      oxidants. Considering the preferential transfusion of FFP from male donors, this
      study aimed at the assessment of FFP units derived from G6PD- males compared with
      control, to show whether they are comparable at physiological, metabolic and
      redox homeostasis levels. Methods: The quality of n = 12 G6PD- and control FFP
      units was tested after 12 months of storage, by using hemolysis, redox, and
      procoagulant activity-targeted biochemical assays, flow cytometry for EV
      enumeration and phenotyping, untargeted metabolomics, in addition to statistical
      and bioinformatics tools. Results: Higher procoagulant activity,
      phosphatidylserine positive EVs, RBC-vesiculation, and antioxidant capacity but
      lower oxidative modifications in lipids and proteins were detected in G6PD- FFP
      compared with controls. The FFP EVs varied in number, cell origin, and
      lipid/protein composition. Pathway analysis highlighted the riboflavin, purine,
      and glycerolipid/glycerophospholipid metabolisms as the most altered pathways
      with high impact in G6PD-. Multivariate and univariate analysis of FFP
      metabolomes showed excess of diacylglycerols, glycerophosphoinositol, aconitate,
      and ornithine but a deficiency in riboflavin, flavin mononucleotide, adenine, and
      arginine, among others, levels in G6PD- FFPs compared with control. Conclusion:
      Our results point toward a different redox, lipid metabolism, and EV profile in
      the G6PD- FFP units. Certain FFP-needed patients may be at greatest benefit of
      receiving FFP intrinsically endowed by both procoagulant and antioxidant
      activities. However, the clinical outcome of G6PD- FFP transfusion would likely
      be affected by various other factors, including the signaling potential of the
      differentially expressed metabolites and EVs, the degree of G6PD-, the redox
      status in the recipient, the amount of FFP units transfused, and probably, the
      storage interval of the FFP, which deserve further investigation by future
      studies.

PMID- 29459897
TI  - Toward the Relevance of Platelet Subpopulations for Transfusion Medicine.
AB  - Circulating platelets consist of subpopulations with different age, maturation
      state and size. In this review, we address the association between platelet size
      and platelet function and summarize the current knowledge on platelet
      subpopulations including reticulated platelets, procoagulant platelets and
      platelets exposing signals to mediate their clearance. Thereby, we emphasize the
      impact of platelet turnover as an important condition for platelet production in
      vivo. Understanding of the features that characterize platelet subpopulations is
      very relevant for the methods of platelet concentrate production, which may
      enrich or deplete particular platelet subpopulations. Moreover, the concept of
      platelet size being associated with platelet function may be attractive for
      transfusion medicine as it holds the perspective to separate platelet
      subpopulations with specific functional capabilities.

PMID- 29459898
TI  - Parotid Quadrantectomy Is a Safe Management for Localized Pleomorphic Adenoma.
AB  - Aim: Pleomorphic adenoma is the most common benign tumor of the parotid gland and
      is classically treated with superficial or total parotidectomy. Less radical
      surgeries have been proposed to minimize the risk of facial nerve injury. The
      oncological safety of these procedures remains controversial. We conducted this
      study to evaluate the safety of superficial hemi-lobectomy (quadrantectomy).
      Patients and methods: Retrospective analysis was conducted on the paraffin
      sections of archived superficial parotidectomy specimens from 11 male and 6
      female patients (median age 33 years). The microscopic extent of extra-capsular
      extension was determined on pathological revision. In addition, prospective
      evaluation of 12 quadrantectomy procedures (M/F = 7/5, median age = 36 years)
      compared to 24 radical surgeries (M = F, median age = 40 years) regarding
      temporary and persistent facial nerve dysfunction on routine clinical assessment
      and recurrence rate. Results: On retrospective pathological revision, pleomorphic
      adenomata had a median microscopic spread of 3 mm beyond capsule in paraffin
      sections (SD = 3.6). On prospective analysis with a median follow-up of 33 months
      (range = 18-54 months), quadrantectomy had similar relative risk of temporary
      facial nerve dysfunction evaluated at the immediate postoperative period as well
      as persistent nerve dysfunction assessed at 3 months (P = 0.701 and P = 0.902,
      respectively). Of the whole study population, one case of recurrence after total
      parotidectomy was observed at mid-term follow-up (P = 1.000). Conclusion: Parotid
      quadrantectomy is a safe management for smaller pleomorphic adenomata localized
      close to one of the two divisions of the facial nerve.

PMID- 29459899
TI  - Structural Changes of RNA in Complex with Proteins in the SRP.
AB  - The structural flexibility of RNA allows it to exist in several shapes and sizes.
      Thus, RNA is functionally diverse and is known to be involved in processes such
      as catalysis, ligand binding, and most importantly, protein recognition. RNA can
      adopt different structures, which can often dictate its functionality. When RNA
      binds onto protein to form a ribonucleoprotein complex (RNP), multiple
      interactions and conformational changes occur with the RNA and protein. However,
      there is the question of whether there is a specific pattern for these changes to
      occur upon recognition. In particular when RNP complexity increases with the
      addition of multiple proteins/RNA, it becomes difficult to structurally
      characterize the overall changes using the current structural determination
      techniques. Hence, there is a need to use a combination of biochemical,
      structural and computational modeling to achieve a better understanding of the
      processes that RNPs are involved. Nevertheless, there are well-characterized
      systems that are evolutionarily conserved [such as the signal recognition
      particle (SRP)] that give us important information on the structural changes of
      RNA and protein upon complex formation.

PMID- 29459901
TI  - Mechanisms and Therapeutic Targets of Cardiac Regeneration: Closing the Age Gap.
AB  - While a regenerative response is limited in the mammalian adult heart, it has
      been recently shown that the neonatal mammalian heart possesses a marked but
      transient capacity for regeneration after cardiac injury, including myocardial
      infarction. These findings evidence that the mammalian heart still retains a
      regenerative capacity and highlights the concept that the expression of distinct
      molecular switches (that activate or inhibit cellular mechanisms regulating
      tissue development and regeneration) vary during different stages of life,
      indicating that cardiac regeneration is an age-dependent process. Thus,
      understanding the mechanisms underpinning regeneration in the neonatal-infarcted
      heart is crucial to develop new treatments aimed at improving cardiovascular
      regeneration in the adult. The present review summarizes the current knowledge on
      the pathways and factors that are known to determine cardiac regeneration in the
      neonatal-infarcted heart. In particular, we will focus on the effects of microRNA
      manipulation in regulating cardiomyocyte proliferation and regeneration, as well
      as on the role of the Hippo signaling pathway and Meis1 in the regenerative
      response of the neonatal-infarcted heart. We will also briefly comment on the
      role of macrophages in scar formation of the adult-infarcted heart or their
      contribution for scar-free regeneration of the neonatal mouse heart after
      myocardial infarction. Although additional research is needed in order to
      identify other factors that regulate cardiovascular regeneration, these pathways
      represent potential therapeutic targets for rejuvenation of aging hearts and for
      improving regeneration of the adult-infarcted heart.

PMID- 29459902
TI  - Whole Brain Parcellation with Pathology: Validation on Ventriculomegaly Patients.
AB  - Numerous brain disorders are associated with ventriculomegaly; normal pressure
      hydrocephalus (NPH) is one example. NPH presents with dementia-like symptoms and
      is often misdiagnosed as Alzheimer's due to its chronic nature and nonspecific
      presenting symptoms. However, unlike other forms of dementia NPH can be treated
      surgically with an over 80% success rate on appropriately selected patients.
      Accurate assessment of the ventricles, in particular its sub-compartments, is
      required to diagnose the condition. Existing segmentation algorithms fail to
      accurately identify the ventricles in patients with such extreme pathology. We
      present an improvement to a whole brain segmentation approach that accurately
      identifies the ventricles and parcellates them into four sub-compartments. Our
      work is a combination of patch-based tissue segmentation and multi-atlas
      registration-based labeling. We include a validation on NPH patients,
      demonstrating superior performance against state-of-the-art methods.

PMID- 29459903
TI  - Editorial: Modifying risk factors - the next step.

PMID- 29459900
TI  - Kruppel-Like Factors in Vascular Inflammation: Mechanistic Insights and
      Therapeutic Potential.
AB  - The role of inflammation in vascular disease is well recognized, involving
      dysregulation of both circulating immune cells as well as the cells of the vessel
      wall itself. Unrestrained vascular inflammation leads to pathological remodeling
      that eventually contributes to atherothrombotic disease and its associated
      sequelae (e.g., myocardial/cerebral infarction, embolism, and critical limb
      ischemia). Signaling events during vascular inflammation orchestrate widespread
      transcriptional programs that affect the functions of vascular and circulating
      inflammatory cells. The Kruppel-like factors (KLFs) are a family of transcription
      factors central in regulating vascular biology in states of homeostasis and
      disease. Given their abundance and diversity of function in cells associated with
      vascular inflammation, understanding the transcriptional networks regulated by
      KLFs will further our understanding of the pathogenesis underlying several
      pervasive health concerns (e.g., atherosclerosis, stroke, etc.) and consequently
      inform the treatment of cardiovascular disease. Within this review, we will
      discuss the role of KLFs in coordinating protective and deleterious responses
      during vascular inflammation, while addressing the potential targeting of these
      critical transcription factors in future therapies.

PMID- 29459904
TI  - Evaluating the Clinical Use of Light-emitting Diode vs Halogen Photocuring Units.
AB  - PURPOSE: To clinically examine the effect of the type of ight-curing unit on the
      light intensity output and to assess different operator variables which affect
      light curing of photo-initiated restorative dental materials, in Damascus, Syria.
      MATERIALS AND METHODS: A total of 185 private dental practices in the Damascus
      area were visited to invite the clinicians to participate in this study. The
      intensity of 163 light-curing units (LCUs) was assessed by radiometry in a
      standard protocol. The age of the curing unit, light tip direction, distance from
      restoration surface, time of exposure and the presence of adherent composite
      remnants on the tip of the light pipe were assessed. Independent samples t-tests
      and ANOVA with Bonferroni post-hoc tests were conducted (p = 0.05). RESULTS: The
      light intensity was affected significantly by the type of the LCU (p < 0.001).
      The increased age of light-curing units significantly reduced the emitted light
      intensity in LED and QTH units (p < 0.05). The presence of adherent resin
      composite remnants on the pipe tip of the curing unit was monitored in 74 cases
      out of 163 (45%). The disinfection wipe was the most common method used to ensure
      infection control of the curing units. CONCLUSION: LED units exhibited a
      significantly better light intensity output at the tip when compared to the QTH
      units. It is important for dentists to consider all practical aspects which can
      influence the efficacy of LCUs in daily practice.

PMID- 29459906
TI  - Assessment of Oral Health Related Quality of Life Among the Institutionalised
      Elderly in Delhi, India.
AB  - PURPOSE: To assess the oral health related quality of life (OHRQoL) among older
      people residing in old-age homes in Delhi, India. MATERIALS AND METHODS: Oral
      health related quality of life was measured by using the Hindi version of
      Geriatric Oral Health Assessment Index (GOHAI) which was tested for its
      reliability and validity. Sociodemographic data were collected and questions
      regarding the self-perception of general health, oral health and perceived need
      for dental treatment were put forward. Clinical assessment was also performed.
      RESULTS: The mean additive-GOHAI score of the study population was found to be
      41.57 +/- 6.07. Statistically significant associations were found between GOHAI
      and perceived measures. GOHAI scores decreased with a decrease in the number of
      teeth present and a decrease in the number of teeth having coronal and root
      caries. Those subjects who were in need of multi-unit prostheses or full
      prostheses had significantly poorer OHRQoL compared to those without any
      prosthetic need or need of single-unit prostheses. CONCLUSION: This study
      revealed the extent of dental problems in old-age home residents and may help to
      plan appropriate preventive measures.

PMID- 29459905
TI  - Perception of Treatment Needs and Use of Dental Services for Children and
      Adolescents with Sickle Cell Disease.
AB  - PURPOSE: To evaluate the perception of treatment needs and the use of dental
      services for children/adolescents with sickle cell disease. MATERIALS AND
      METHODS: A cross-sectional study was conducted with 250 children/adolescents with
      sickle cell disease at a reference center in the city of Recife, Brazil. Data on
      the use of dental services were collected using a 13-item questionnaire
      administered to parents/guardians. The examiner in charge of determining l caries
      and periodontal status had previously undergone a training and calibration
      exercise. Descriptive statistics and Poisson regression analysis were also
      performed (alpha = 5%). RESULTS: A total of 47.2% of the children/adolescents
      with sickle cell disease were diagnosed with caries and 14.0% were diagnosed with
      some periodontal problems. The following variables were statistically
      significantly associated with the perceptions of parents/guardians regarding the
      treatment needs of their children: caries (PR = 1.24; 95%CI: 1.09-1.42),
      periodontal problems (PR = 1.10; 95%CI 1.01-1.20) and history of toothache in the
      previous six months (PR = 1.17; 95%CI 1.06-1.29). Only a lower level of mothers'
      schooling (PR = 1.64; 95%CI 1.06-2.53) was statistically significantly associated
      with the mean number of caries among the children/adolescents with sickle cell
      disease. Mean dmft/DMFT indices were higher among children/adolescents who sought
      dental care. CONCLUSION: Based on our results, a predomination of curative
      treatment was found, as seeking out dental treatment was more frequent among
      children/adolescents with a greater number of caries.

PMID- 29459907
TI  - Impact of Chronic Kidney Disease Mineral and Bone Disorder on Jaw and Alveolar
      Bone Metabolism: A Narrative Review.
AB  - Chronic kidney disease (CKD) has become a worldwide public health problem. It is
      estimated that nearly 90% of patients with chronic renal failure manifest some
      symptoms of oral disease. With advances in medical treatment, CKD patients are
      living longer and require oral care. Chronic kidney disease is often accompanied
      by disturbances in mineral metabolism which are classified as their own clinical
      entity known as CKD-mineral and bone disorder (CKD-MBD). CKD-MBD affects all
      aspects of bone physiology: bone volume, bone turnover and bone mineralization.
      Jaw bones affected with CKD-MBD can have important clinical implications for the
      survival and osseointegration of dental implants, success of bone regeneration
      therapy, and increased risk of bone loss in patients with periodontitis or risk
      of bone fracture. Assessment of bone turnover is the most important diagnostic
      tool to monitor progression of CKD-MBD. Bone biomarkers and radiographical
      examination of bone density may be particularly useful to both, diagnosis and
      monitoring of bone turnover. Cone beam computed tomography (CBCT) as a reliable
      method with many advantages over other radiographic methods can be used for
      analysis of jaw bone micro-architectural changes and may be of a great help in
      bone quality determination in CKD-MBD.

PMID- 29459908
TI  - Trends in Early Childhood Caries: An Italian Perspective.
AB  - PURPOSE: To evaluate the prevalence of early childhood caries (ECC) and severe
      ECC (S-ECC) among Italian preschool children and its predictors regarding
      children's lifestyle. MATERIALS AND METHODS: A cross-sectional study was carried
      out involving 563 preschool children. A questionnaire for children's parents and
      clinical examinations were conducted by calibrated, blinded examiners. The odds
      ratios (OR) for ECC or S-ECC and co-presence of risk factors were calculated
      using univariate and multivariate models. Statistical significance was set at p <
      0.05 in all analyses. RESULTS: The prevalence of ECC and S-ECC was 14.4% and
      5.9%, respectively. According to the multivariate analysis, the predictors for
      caries were (p < 0.05): age (OR = 2.5; 95% CI = 1.36 - 4.52), non-Italian ethnic
      origin (OR = 4.3; 95% CI = 2.83 - 7.37), consumption of sugary beverages more
      than once per day (OR = 2.1; 95% CI = 1.21 - 5.26) and having inadequate oral
      hygiene status (OR = 3.6; 95% CI = 2.01 - 5.83). CONCLUSIONS: Dietary habits and
      dental care are important environmental contributing factors in the development
      of caries in preschool children. Oral health promotion should include an oral
      hygiene instruction programme and dietary guidelines focused on daily sugar
      intake for the preschool children themselves as well as for their parents.

PMID- 29459909
TI  - Determining Caries Activity Using Oratest Among 12-to 15-year-old Children.
AB  - PURPOSE: Dental caries is the primary pathological cause of early tooth loss in
      children, which may lead to malnutrition and other health problems.
      Identification of patients with active carious lesions and at high risk for
      caries can help to dramatically decrease the disease prevalence. Thus,
      recognising the importance of early diagnosis of caries, the present study was
      carried out to correlate caries with oral microflora using Oratest among 12- to
      15-year-old schoolchildren. MATERIALS AND METHODS: A total of 100 children were
      divided into control and test groups (n = 50) according to their DMFT scores. The
      test group was further divided into subgroup 1 (DMFT = 1-3) and subgroup 2 (DMFT
      > 3). Oratest, a caries activity test, was performed on all the children.
      Comparison among the variables was done using ANOVA and the independent sample t
      test. RESULTS: Boys had lower DMFT values (1.35 +/- 0.2) than did girls (1.67 +/-
      0.2) (p = 0.38), and the Oratest time was higher among boys (132.8 +/- 0.5 min)
      than girls (126.4 +/- 0.5 min) (p = 0.53). The control group had the highest mean
      Oratest time (172.7 +/- 0.3 min), followed by subgroup 1 (97.8 +/- 0.2 min), and
      subgroup 2 had the lowest Oratest time (68.5 +/- 14.8 min). A statistically
      significant negative correlation (r = -0.893) was found between the mean DMFT and
      the Oratest time (p < 0.001), ie, they were inversely related to each other.
      CONCLUSION: An inverse relationship exists between Oratest and DMFT score.

PMID- 29459910
TI  - Fabrication of tough epoxy with shape memory effects by UV-assisted direct-ink
      write printing.
AB  - 3D printing of epoxy-based shape memory polymers with high mechanical strength,
      excellent thermal stability and chemical resistance is highly desirable for
      practical applications. However, thermally cured epoxy in general is difficult to
      print directly. There have been limited numbers of successes in printing epoxy
      but they suffer from relatively poor mechanical properties. Here, we present an
      ultraviolet (UV)-assisted 3D printing of thermally cured epoxy composites with
      high tensile toughness via a two-stage curing approach. The ink containing UV
      curable resin and epoxy oligomer is used for UV-assisted direct-ink write (DIW)
      based 3D printing followed by thermal curing of the part containing the epoxy
      oligomer. The UV curable resin forms a network by photo polymerization after the
      1st stage of UV curing, which can maintain the printed architecture at an
      elevated temperature. The 2nd stage thermal curing of the epoxy oligomer yields
      an interpenetrating polymer network (IPN) composite with highly enhanced
      mechanical properties. It is found that the printed IPN epoxy composites enabled
      by the two-stage curing show isotropic mechanical properties and high tensile
      toughness. We demonstrated that the 3D-printed high-toughness epoxy composites
      show good shape memory properties. This UV-assisted DIW 3D printing via a two
      stage curing method can broaden the application of 3D printing to fabricate
      thermoset materials with enhanced tensile toughness and tunable properties for
      high-performance and functional applications.

PMID- 29459911
TI  - Effects of a 12-week high-alpha-linolenic acid intervention on EPA and DHA
      concentrations in red blood cells and plasma oxylipin pattern in subjects with a
      low EPA and DHA status.
AB  - The essential omega-3 fatty acid alpha-linolenic acid (ALA, 18:3n3) can be
      converted into EPA and DHA. The aim of the present study was to determine the
      effect of a high-ALA diet on EPA and DHA levels in red blood cells (RBCs) and
      their oxylipins in the plasma of subjects with a low EPA and DHA status. Fatty
      acid concentrations [MUg mL-1] and relative amounts [% of total fatty acids] in
      the RBCs of 19 healthy men (mean age 26.4 +/- 4.6 years) were analyzed by means
      of GC-FID. Free plasma oxylipin concentrations were determined by LC-MS based
      targeted metabolomics. Samples were collected and analyzed at baseline (week 0)
      and after 1 (week 1), 3 (week 3), 6 (week 6), and 12 (week 12) weeks of high
      dietary ALA intake (14.0 +/- 0.45 g day-1). ALA concentrations significantly (p <
      0.001) increased from 1.44 +/- 0.10 (week 0) to 4.65 +/- 0.22 (week 1), 5.47 +/-
      0.23 (week 3), 6.25 +/- 0.24 (week 6), and 5.80 +/- 0.28 (week 12) MUg mL-1. EPA
      concentrations increased from 6.13 +/- 0.51 (week 0) to 7.33 +/- 0.33 (week 1),
      8.38 +/- 0.42 (p = 0.021, week 3), 10.9 +/- 0.67 (p < 0.001, week 6), and 11.0 +/
      0.64 (p < 0.001, week 12) MUg mL-1. DHA concentrations unexpectedly decreased
      from 41.0 +/- 1.93 (week 0) to 37.0 +/- 1.32 (week 1), 36.1 +/- 1.37 (week 3),
      35.1 +/- 1.06 (p = 0.010, week 6), and 30.4 +/- 1.09 (p < 0.001, week 12) MUg mL
      1. Relative SigmaEPA + DHA amounts were unchanged during the intervention (week
      0: 4.63 +/- 0.19, week 1: 4.67 +/- 0.16, week 3: 4.61 +/- 0.13, week 6: 4.73 +/-
      0.15, week 12: 4.52 +/- 0.11). ALA- and EPA-derived hydroxy- and dihydroxy-PUFA
      increased similarly to their PUFA precursors, although in the case of ALA-derived
      oxylipins, the concentrations increased less rapidly and to a lesser extent
      compared to the concentrations of their precursor FA. LA-derived oxylipins
      remained unchanged and arachidonic acid and DHA oxylipin concentrations were not
      significantly changed. Our results confirm that the intake of ALA is not a
      sufficient source for the increase of EPA + DHA in subjects on a Western diet.
      Specifically, a high-ALA diet results in increased EPA and declined DHA
      concentrations. However, the changes effectively balance each other out so that
      SigmaEPA + DHA in RBCs - which is an established marker for health protective
      effects of omega-3-PUFA - remains constant. The PUFA levels in RBCs reflect the
      concentration and its changes in plasma hydroxy- and dihydroxy-PUFA
      concentrations for ALA and EPA.

PMID- 29459912
TI  - Mechanistic insight into the in vitro toxicity of graphene oxide against biofilm
      forming bacteria using laser-induced breakdown spectroscopy.
AB  - While the cytotoxicity of graphene oxide (GO) has been well established, its
      bactericidal mechanism, however, has yet to be elucidated to advance GO-based
      biomedical and environmental applications. In an attempt to better understand the
      bactericidal action of GO, herein we studied the interactions of GO with Gram
      negative Escherichia coli and Gram-positive Staphylococcus aureus cells using
      physical techniques and chemical probes, respectively. In particular, a novel
      laser-induced breakdown spectroscopy (LIBS) based elemental fingerprint analysis
      revealed notable differences between viable and non-viable cells based on the
      difference in the concentration of trace inorganic elements in complex bacterial
      systems, which reflect cellular membrane integrity. Lower emission intensities
      from essential inorganic ions in the GO-treated cells offered explicit evidence
      on the efflux of intracellular molecules from the bacteria through damaged cell
      membranes. Furthermore, a detailed structural and morphological investigation of
      bacterial membrane integrity confirmed GO-induced membrane stress upon direct
      contact interactions with bacterial cells, resulting in the disruption of
      cellular membranes. Moreover, the generation of intracellular reactive oxygen
      species (ROS) in the presence of an added antioxidant underlined the role of GO
      mediated oxidative stress in bacterial cell inactivation. Thus, by correlating
      the changes in the bacterial elemental compositions with the severe morphological
      alterations and the high ROS production witnessed herein, we propose that the
      bactericidal mechanism of GO is likely to be the synergy between membrane and
      oxidative stress towards both tested species. Our findings offer useful
      guidelines for the future development of GO-based antibacterial surfaces and
      coatings.

PMID- 29459914
TI  - Tandem MoP nanocrystals with rich grain boundaries for efficient electrocatalytic
      hydrogen evolution.
AB  - Constructing surface disorder including grain boundaries, stacking faults, and
      dislocation arrays in nanomaterials is an important strategy to enhance the
      catalytic activity of nanocatalysts. Here we report the facile synthesis of
      crystallographically interconnected MoP nanocrystals with abundant grain
      boundaries. They exhibit outstanding electrocatalytic activities for hydrogen
      evolution.

PMID- 29459915
TI  - Microfluidic label-free selection of mesenchymal stem cell subpopulation during
      culture expansion extends the chondrogenic potential in vitro.
AB  - Mesenchymal stem cells (MSCs) have been shown as potential candidates for cell
      based therapies for a diverse range of tissue regenerative applications.
      Therapeutic use of MSCs usually requires culture expansion, which increases the
      heterogeneity of MSCs in vitro, thus affecting the potency of the MSCs for more
      specific indications. The capacity for identifying and isolating special subsets
      of MSCs for treatment of specific diseases therefore holds great clinical
      significance. An important therapeutic application of MSC is for the regeneration
      of cartilage tissue. We and others have previously developed label-free
      microfluidic means to isolate subpopulations of culture expanded MSCs based on
      distinct biophysical characteristics. Here we utilize a spiral micro-channel
      device to separate culture expanded MSCs into five subgroups according to cell
      size, and study their proliferation and chondrogenesis at early, middle and late
      passages. Results show that in all passages, the medium-size subpopulation (cell
      size of 17-21 MUm), compared to other subpopulations, displays significantly
      higher proliferation rate and chondrogenic capacity in terms of cartilage
      extracellular matrix formation. Also, the small cell subpopulation (average cell
      size of 11-12 MUm) shows lower viability, and large cell subpopulation (average
      cell size 23-25 MUm) expresses higher level of senescence-associated beta
      galactosidase. Finally, we show that repeated microfluidic exclusion of MSCs
      larger than 21 MUm and smaller than 17 MUm at every passage during continuous
      culture expansion result in selected MSCs with faster proliferation and better
      chondrogenic potential as compared to MSC derived from conventional expansion
      approach. This study demonstrates the significant merit and utility of size-based
      cell selection for the application of MSCs in cartilage regeneration.

PMID- 29459916
TI  - UV-induced long-lived decays in solvated pyrimidine nucleosides resolved at the
      MS-CASPT2/MM level.
AB  - The most relevant 'dark' electronic excited states in DNA/RNA pyrimidine
      nucleosides are mapped in water employing hybrid MS-CASPT2/MM optimisations with
      explicit solvation and including the sugar. Conical intersections (CIs) between
      initially accessed bright 1pipi* and the lowest energy dark 1npi* excited states,
      involving the lone pair localised on the oxygen and/or nitrogen atoms are
      characterised. They are found in the vicinities of the Franck-Condon (FC) region
      and are shown to facilitate non-adiabatic population transfer. The excited state
      population of the 1nOpi* state, localised in the carbonyl moiety on all
      pyrimidine nucleosides, is predicted to rapidly evolve to its minimum, displaying
      non-negligible potential energy barriers along its non-radiative decay, and
      accounting for the ps signal registered in pump-probe experiments as well as for
      an efficient population of the triplet state. Cytidine displays an additional
      1nNpi* state localised in the N3 atom and that leads to its excited state minimum
      displaying large potential energy barriers in the pathway connecting to the CI
      with the ground state. Sugar-to-base hydrogen/proton transfer processes are
      assessed in solution for the first time, displaying a sizable barrier along its
      decay and thus being competitive with other slow decay channels in the ps and ns
      timescales. A unified deactivation scheme for the long-lived channels of
      pyrimidine nucleosides is delivered, where the 1nOpi* state is found to mediate
      the long-lived decay in the singlet manifold and act as the doorway for triplet
      population and thus accounting for the recorded phosphorescence and, more
      generally, for the transient/photoelectron spectral signals registered up to the
      ns timescale.

PMID- 29459919
TI  - Quantifying atom-scale dopant movement and electrical activation in Si:P
      monolayers.
AB  - Advanced hydrogen lithography techniques and low-temperature epitaxial overgrowth
      enable the patterning of highly phosphorus-doped silicon (Si:P) monolayers (ML)
      with atomic precision. This approach to device fabrication has made Si:P
      monolayer systems a testbed for multiqubit quantum computing architectures and
      atomically precise 2-D superlattice designs whose behaviors are directly tied to
      the deterministic placement of single dopants. However, dopant segregation,
      diffusion, surface roughening, and defect formation during the encapsulation
      overgrowth introduce large uncertainties to the exact dopant placement and
      activation ratio. In this study, we develop a unique method by combining dopant
      segregation/diffusion models with sputter profiling simulation to monitor and
      control, at the atomic scale, dopant movement using room-temperature grown
      locking layers (LLs). We explore the impact of LL growth rate, thickness, rapid
      thermal annealing, surface accumulation, and growth front roughness on dopant
      confinement, local crystalline quality, and electrical activation within Si:P 2-D
      systems. We demonstrate that dopant movement can be more efficiently suppressed
      by increasing the LL growth rate than by increasing the LL thickness. We find
      that the dopant segregation length can be suppressed below a single Si lattice
      constant by increasing the LL growth rates at room temperature while maintaining
      epitaxy. Although dopant diffusivity within the LL is found to remain high (on
      the order of 10-17 cm2 s-1) even below the hydrogen desorption temperature, we
      demonstrate that exceptionally sharp dopant confinement with high electrical
      quality within Si:P monolayers can be achieved by combining a high LL growth rate
      with low-temperature LL rapid thermal annealing. The method developed in this
      study provides a key tool for 2-D fabrication techniques that require precise
      dopant placement to suppress, quantify, and predict a single dopant's movement at
      the atomic scale.

PMID- 29459920
TI  - Amplification-free detection of DNA in a paper-based microfluidic device using
      electroosmotically balanced isotachophoresis.
AB  - We present a novel microfluidic paper-based analytical device (MUPAD) which
      utilizes the native high electroosmotic flow (EOF) in nitrocellulose to achieve
      stationary isotachophoresis (ITP) focusing. This approach decouples sample
      accumulation from the length of the channel, resulting in significant focusing
      over short channel lengths. We provide a brief theory for EOF-balanced ITP
      focusing under continuous injection from a depleting reservoir and present the
      design of a short (7 mm) paper-based microfluidic channel, which allows a 200 MUL
      sample to be processed in approximately 6 min, resulting in a 20 000-fold
      increase in concentration - a full order of magnitude improvement compared to
      previous paper-based ITP devices. We show the stability of the assay over longer
      (40 min) durations of time, and using Morpholino probes, we present the
      applicability of the device for amplification-free detection of nucleic acids,
      with a limit-of-detection (LoD) of 5 pM in 10 min. Finally, we utilize the small
      footprint of the channel and show a multiplexed platform in which 12 assays
      operate in parallel in a 24-well plate format.

PMID- 29459921
TI  - Extension of antiaromatic norcorrole by cycloaddition.
AB  - The antiaromatic ring of norcorrole, a contracted tetrapyrrolic porphyrinoid, was
      subjected to [2+3] dipolar cycloaddition of iminonitriles. The paratropic
      character of the resulting chiral chlorins was retained. The chlorins were easily
      dehydrogenated in the presence of air, yielding pyrazole-fused norcorroles with
      markedly enhanced paratropicity.

PMID- 29459922
TI  - Templated synthesis of atomically-thin Ag nanocrystal catalysts in the
      interstitial space of a layered silicate.
AB  - Enclosing functional nanoparticles in stable inorganic supports is important for
      generating ultra-stable catalytic active sites with good performance and material
      utilization efficiency. Here we describe a simple method to synthesize ultra-thin
      Ag nanocrystals with dimensions that are defined by the ~1.4 nm 2D interlayer
      separating a layered silicate nanostructure. We call the particles "nanoplates"
      because they are <1.4 nm thick in one direction and their in-plane dimensions are
      defined by reaction time. The layered silicate is pillared with dialkylurea,
      which serves both as a reducing agent for the Ag precursor and immobilizes the Ag
      nanoplates in the interstitial nanospace. The supported Ag nanoplates showed
      catalytic activity for hydrolysis of NH3BH3 and generation of H2 at room
      temperature. These supported Ag nanocatalysts had performance much higher than
      spherical Ag nanoparticles. They, moreover, had performance and stability
      comparable to costly supported Pt nanoparticles.

PMID- 29459924
TI  - Catalytic asymmetric inverse electron demand Diels-Alder reaction of fulvenes
      with azoalkenes.
AB  - An unprecedented copper(i)-catalyzed asymmetric inverse electron demand Diels
      Alder reaction of azoalkenes with fulvenes is reported. This methodology offers a
      directed entry to synthesize bicyclic tetrapyridazine derivatives in good yield
      with exclusive regioselectivity and excellent stereoselectivity.

PMID- 29459925
TI  - Investigation of hydrophobic substrates for solution residue analysis utilizing
      an ambient desorption liquid sampling-atmospheric pressure glow discharge
      microplasma.
AB  - A practical method for preparation of solution residue samples for analysis
      utilizing the ambient desorption liquid sampling-atmospheric pressure glow
      discharge optical emission spectroscopy (AD-LS-APGD-OES) microplasma is
      described. Initial efforts involving placement of solution aliquots in wells
      drilled into copper substrates, proved unsuccessful. A design-of-experiment (DOE)
      approach was carried out to determine influential factors during sample
      deposition including solution volume, solute concentration, number of droplets
      deposited, and the solution matrix. These various aspects are manifested in the
      mass of analyte deposited as well as the size/shape of the product residue.
      Statistical analysis demonstrated that only those initial attributes were
      significant factors towards the emission response of the analyte. Various
      approaches were investigated to better control the location/uniformity of the
      deposited sample. Three alternative substrates, a glass slide, a
      poly(tetrafluoro)ethylene (PTFE) sheet, and a polydimethylsiloxane (PDMS)-coated
      glass slide, were evaluated towards the microplasma analytical performance. Co
      deposition with simple organic dyes provided an accurate means of determining the
      location of the analyte with only minor influence on emission responses. The PDMS
      coated glass provided the best performance by virtue of its providing a uniform
      spatial distribution of the residue material. This uniformity yielded an improved
      limits of detection by approximately 22* for 20 MUL and 4 x for 2 MUL over the
      other two substrates. While they operate by fundamentally different processes,
      this choice of substrate is not restricted to the LS-APGD, but may also be
      applicable to other AD methods such as DESI, DART, or LIBS. Further developments
      will be directed towards a field-deployable ambient desorption OES source for
      quantitative analysis of microvolume solution residues of nuclear forensics
      importance.

PMID- 29459926
TI  - Palladium-catalyzed dimerization of N-aryl propargylamines for the synthesis of 3
      vinylquinolines.
AB  - A straightforward method for the synthesis of polyfunctionalized quinolines from
      readily available N-aryl propargylamines under aerobic conditions was developed.
      It provides convenient access to a variety of synthetically and pharmaceutically
      important quinolines in moderate to good yields. Control experiments suggest that
      the cascade reaction might proceed via the Pd-catalyzed electrophilic cyclization
      of N-aryl propargylamines followed by a hydroarylation process through trapping
      of the sigma-quinolinylpalladium intermediate with a second molecule of the
      substrate.

PMID- 29459927
TI  - Silver-mediated direct C-H amination of BODIPYs for screening endoplasmic
      reticulum-targeting reagents.
AB  - A highly efficient direct C-H amination of BODIPYs has been accomplished through
      the Ag(i)-mediated nucleophilic addition of an amino radical to BODIPY at the C3-
      and/or C5-position and deprotonation processes under mild conditions. This
      protocol greatly streamlines the access to a variety of 3-aminated and 3,5
      diaminated BODIPYs. The resulting BODIPYs with morpholine groups (3q and 4b)
      exhibit specific endoplasmic reticulum (ER)-localization capacities and
      negligible cytotoxicities, which would be potential ER-targeting reagents.

PMID- 29459928
TI  - Nano-graphene oxide-UCNP-Ce6 covalently constructed nanocomposites for NIR
      mediated bioimaging and PTT/PDT combinatorial therapy.
AB  - NIR light-induced imaging-guided cancer therapy is an encouraging route in the
      cancer theranostic field. Herein, we describe a novel nanoscale proposal, which
      is established by covalently implanting core-shell structured upconversion
      nanoparticles (UCNPs) with nanographene oxide (NGO) by a process utilizing
      polyethylene glycol (PEG), and consequently loading Chlorin e6 (Ce6) onto the
      surface of NGO. The acquired NGO-UCNP-Ce6 (NUC) nanocomposites can not only be
      employed as upconversion luminescence (UCL) imaging probes of cells and whole
      body animals with high contrast for diagnosis, but also can generate reactive
      oxygen species (ROS) under 808 nm light excitation for photodynamic therapy
      (PDT); over and above, they can swiftly and proficiently translate the 808 nm
      photon into thermal energy for photothermal therapy (PTT). An extraordinarily
      enhanced and synchronized therapeutic effect paralleled to the individual PTT or
      PDT is achieved, rendering extraordinary therapeutic effectiveness for cancer
      treatment. Consequently, profiting from this inimitable multifunctional
      nanohybrid, the NUCs synthesized here are encouraging as a cohesive theranostic
      probe for impending UCL imaging-guided combinatorial PDT/PTT.

PMID- 29459930
TI  - Optimizing interfacial transport properties of InO2 single atomic layers in
      In2O3(ZnO)4 natural superlattices for enhanced high temperature thermoelectrics.
AB  - In2O3(ZnO)k natural superlattices (where k is an integer), consisting of
      relatively earth abundant and non-toxic elements with coarsening-resistant
      nanostructures, are environmentally friendly materials with the potential for
      high temperature thermoelectric applications. Herein, we report our investigation
      of the high temperature thermoelectric properties of the In2O3(ZnO)4 superlattice
      bulk polycrystals that were singly and dually doped with Al and Ce. Transport
      property measurements revealed that Al and Ce did not only enter the ZnO blocks
      but also modified the InO2 single atomic layers. The effective electron potential
      barrier height of the superlattice interfaces can be adjusted by doping, and the
      optimal value that maximizes the power factor is of the order of kBT above the
      Fermi level. The interfacial thermal (Kapitza) resistance of the InO2 atomic
      sheets dramatically increased with doping, primarily accounting for the bulk
      thermal conductivity reduction. At the optimal crossing of the interfacial
      thermal resistance and the effective potential barrier height, a maximum ZT of
      ~0.22 was achieved at 800  degrees C in the 1.6 mol% Al-doped superlattice, which
      was an enhancement of ~200% over the pristine In2O3(ZnO)4. This work provides a
      new perspective on enhancing the high temperature thermoelectric performance of
      nanostructured oxides by synergistically optimizing the interfacial phonon and
      electron transport properties.

PMID- 29459931
TI  - Versatile reactivities of rare-earth metal dialkyl complexes supported by a
      neutral pyrrolyl-functionalized beta-diketiminato ligand.
AB  - Herein, rare-earth metal dialkyl complexes supported by a neutral pyrrolyl
      functionalized beta-diketiminato ligand with the formula LRE(CH2SiMe3)2(thf) (RE
      = Y (1a), Dy (1b), Er (1c), Yb (1d); L = MeC(NDipp)CHC(Me)NCH2CH2NC4H2-2,5-Me2,
      Dipp = 2,6-iPr2C6H3) were synthesized via the reactions of the beta-diketimine HL
      with the rare-earth metal trialkyl complexes RE(CH2SiMe3)3(thf)2 in high yields.
      The reactivities of 1 with pyridine derivatives, unsaturated substrates, and
      elemental sulfur were investigated, and some interesting chemical transformations
      were observed. Ligand exchange and activation of sp2 and sp3 C-H bonds occurred
      during the reactions with pyridine derivatives to afford different types of
      mononuclear rare-earth metal pyridyl complexes, namely, LEr(CH2SiMe3)2(eta1
      NC5H4) (2c), LRE(eta3-CH2-2-NC5H2-4,6-Me2)2 (RE = Y (3a), Er (3c)), and
      LRE(CH2SiMe3)(eta2-(C,N)-2-(2-C6H4NC5H4)) (RE = Er (4c), Yb = (4d)). Similarly,
      activation of the sp C-H bond occurred during the reaction of phenylacetylene
      with 1c to produce the dinuclear erbium alkynyl complex [LEr(CH2SiMe3)(MU
      C[triple bond, length as m-dash]CPh)]2 (5c). The mixed amidinate-beta
      diketiminato ytterbium complex LYb[(Dipp)NC(CH2SiMe3)N(Dipp)](CH2SiMe3) (6d) was
      obtained by the insertion of bis(2,6-diisopropylphenyl)carbodiimide into a Yb
      alkyl bond, as well as via the direct alkane elimination of a CH2SiMe3 moiety
      with bis(2,6-diisopropylphenyl)formamidine to afford the erbium complex
      LEr(DippNCHNDipp)(CH2SiMe3) (7c). A rare sp2 C-H bond oxidation of the beta
      diketiminato backbone with elemental sulfur insertion was detected to provide the
      unprecedented dinuclear rare-earth metal thiolate complexes (LRE)2(MU
      SCH2SiMe3)2(MU-SCC(Me)(NDipp)C(Me)NCH2CH2NC4H2Me2-2,5) (RE = Y (8a), Er (8c)) in
      the reactions of S8 with 1a and 1c, respectively. The molecular structures of the
      complexes 1-8 were determined by single-crystal X-ray diffraction analyses.

PMID- 29459932
TI  - Carbene insertion into N-H bonds with size-selectivity induced by a microporous
      ruthenium-porphyrin metal-organic framework.
AB  - A stable and porous porphyrinic metal-organic framework, Ru-PMOF-1(Hf), has been
      prepared through the self-assembly of [5,10,15,20-tetrakis(4
      carboxyphenyl)porphyrinato](monocarbonyl)ruthenium (Ru(TCPP)(CO)) and HfCl4.
      Single-crystal X-ray diffraction analysis reveals that Ru-PMOF-1(Hf) possesses a
      three-dimensional (3D) structure with orthogonal 1D open channels of 1.9 * 1.9
      nm2. The porous nature has been confirmed by gas adsorption measurements. Its
      catalytic activity for the carbene insertion into N-H bonds has been
      investigated. The catalytic results indicate that Ru-PMOF-1(Hf) is efficient for
      the insertion reactions of ethyl 2-diazoacetate (EDA) into a range of secondary
      amines with up to 92% yield, 938 TON and 2475 h-1 TOF. As an excellent
      heterogeneous catalyst, Ru-PMOF-1(Hf) can be recovered and reused for at least
      ten runs with negligible loss of catalytic activity. Due to its uniform
      microporosity in three orthogonal directions, Ru-PMOF-1(Hf), of which the
      particle sizes were carefully controlled by sieving, can induce size selectivity
      regarding the amine substrates. The reactivities of different unbranched
      dialkylamines, such as diethylamine (NHEt2), dibutylamine (NHBu2) and
      dipentylamine (NHPent2), have been compared, and the results display an apparent
      decreasing trend along the chain lengthening. For comparison, the corresponding
      nonporous and homogeneous catalyst Ru(TMCPP)(CO) (TMCPP = tetrakis(4
      methoxycarbonylphenyl)porphyrin) displays negligible difference towards the
      reactions with these three amines.

PMID- 29459933
TI  - Urinary benzophenone-type UV filters in people living in South China: rural
      versus urban areas.
AB  - Benzophenone (BP)-type UV filters are widely used in sunscreen products to
      protect human skin from UV radiation. However, only a few studies have been
      conducted to determine the level of human exposure to BPs in rural areas of
      China. In this study, we evaluated the exposure levels of people living in three
      villages and a city in South China to five major BPs (BP-1, BP-2, BP-3, BP-8, and
      4-OH-BP). The detection rates of BP-1, BP-3, and 4-OH-BP were 66%, 72%, and 75%,
      respectively, in rural areas and 85%, 75%, and 80%, correspondingly, in urban
      areas. BP-2 and BP-8 were rarely detected. The results indicated that people
      living in South China are extensively exposed to BPs, regardless of sampling
      sites (rural and urban areas). The observed concentrations of BP-1 (urban vs.
      rural = 1.04 ng mL-1vs. 0.21 ng mL-1) and BP-3 (0.37 ng mL-1vs. 0.16 ng mL-1)
      were significantly (one-way ANOVA, p < 0.01) lower in the rural areas than in the
      urban areas. BP-1 (59%) based on composition profile analysis was the dominant BP
      derivative in urine samples of urban residents, whereas 4-OH-BP (36%) was the
      most prevalent BP in rural areas. In the rural areas, significant positive
      correlations between urinary BP-1 and BP-3 (r = 0.529, p < 0.01) and between
      urinary BP-1 and 4-OH-BP (r = 0.323, p < 0.05) concentrations were obtained; in
      the urban areas, we only observed a clear correlation (p < 0.01) between BP-1 and
      4-OH-BP. The different composition profiles and associations among urinary BPs
      indicated that exposure sources of BPs might be different between rural and urban
      areas. The distribution profiles of BP-1 and its parent compound (i.e., BP-3) in
      urine decreased with the age of adults (r = -0.410, p < 0.01) in the rural areas.

PMID- 29459934
TI  - A planar impedance sensor for 3D spheroids.
AB  - Three dimensional cell culture systems have witnessed rapid expansion in the
      fields of tissue engineering and drug testing owing to their inherent ability to
      mimic native tissue microenvironments. High throughput technologies have also
      facilitated rapid and reproducible generation of spheroids and subsequently their
      use as in vitro tissue models in drug screening platforms. However, drug
      screening technologies are in need of monitoring platforms to study these 3D
      culture models. In this work we present a novel platform to measure the
      electrical impedance of 3D spheroids, through the use of a planar organic
      electrochemical transistor (OECT) and a novel circular-shaped microtrap. A new
      strategy was generated to overcome incompatibility of the integration of
      polydimethylsiloxane (PDMS) microdevices with OECT fabrication. The impedance
      platform for 3D spheroids was tested by using spheroids formed from mono-cultures
      of fibroblast and epithelial cells, as well as co-culture of the two cell types.
      We validated the platform by showing its ability to measure the spheroid
      resistance (Rsph) of the 3D spheroids and differences in Rsph were found to be
      related to the ion permeability of the spheroid. Additionally, we showed the
      potential use of the platform for the on-line Rsph monitoring when a co-culture
      spheroid was exposed to a porogenic agent affecting the integrity of the cell
      membrane.

PMID- 29459936
TI  - Maternal Microbiota, Prepregnancy Weight, and Mode of Delivery: Intergenerational
      Transmission of Risk for Childhood Overweight and Obesity.

PMID- 29459935
TI  - Association of Cigarette, Cigar, and Pipe Use With Mortality Risk in the US
      Population.
AB  - Importance: Tobacco products have changed in recent years. Contemporary mortality
      risk estimates of combustible tobacco product use are needed. Objective: To
      investigate the mortality risks associated with current and former use of cigars,
      pipes, and cigarettes. Design, Setting, and Participants: The National
      Longitudinal Mortality Study is a longitudinal population-based, nationally
      representative health survey with mortality follow-up that includes demographic
      and other information from the Current Population Survey, tobacco product use
      information from the Tobacco Use Supplement, and mortality data from the National
      Death Index. In this study, participants provided tobacco use information at
      baseline in surveys starting from 1985 and were followed for mortality through
      the end of 2011. The study includes 357 420 participants who reported exclusively
      using cigar, pipes, or cigarettes or reported never using any type of tobacco
      product. Exposures: Current or former exclusive use of any cigar (little cigar,
      cigarillos, large cigar), traditional pipe, or cigarette and never tobacco use.
      Information on current daily and nondaily use was also collected. Estimates
      adjusted for age, sex, race/ethnicity, education, and survey year. Main Outcomes
      and Measures: All-cause and cause-specific mortality as identified as the primary
      cause of death from death certificate information. Results: Of the 357 420
      persons included in the analysis, the majority of current and former cigar and
      pipe smokers were male (79.3%-98.0%), and smokers were more evenly divided by sex
      (46% of current daily smokers were male). There were 51 150 recorded deaths
      during follow-up. Exclusive current cigarette smokers (hazard ratio [HR], 1.98;
      95% CI, 1.93-2.02) and exclusive current cigar smokers (HR, 1.20; 95% CI, 1.03
      1.38) had higher all-cause mortality risks than never tobacco users. Exclusive
      current cigarette smokers (HR, 4.06; 95% CI, 3.84-4.29), exclusive current cigar
      smokers (HR, 1.61; 95% CI, 1.11-2.32), and exclusive current pipe smokers (HR,
      1.58; 95% CI, 1.05-2.38) had an elevated risk of dying from a tobacco-related
      cancer (including bladder, esophagus, larynx, lung, oral cavity, and pancreas).
      Among current nondaily cigarette users, statistically significant associations
      were observed with deaths from lung cancer (HR, 6.24; 95% CI, 5.17-7.54), oral
      cancer (HR, 4.62; 95% CI, 1.84-11.58), circulatory death (HR, 1.43; 95% CI, 1.30
      1.57), cardiovascular death (HR, 1.24; 95% CI, 1.11-1.39), cerebrovascular death
      (stroke) (HR, 1.39; 95% CI, 1.12-1.74), and chronic obstructive pulmonary disease
      (HR, 7.66; 95% CI, 6.09-9.64) as well as for daily smokers. Conclusions and
      Relevance: This study provides further evidence that exclusive use of cigar,
      pipes, and cigarettes each confers significant mortality risks.

PMID- 29459937
TI  - Treating Sepsis Is Complicated: Are Governmental Regulations for Sepsis Care Too
      Simplistic?

PMID- 29459938
TI  - Antiepileptic Drugs in Pregnancy-Quick Decisions With Long-term Consequences.

PMID- 29459940
TI  - Time to Release Medicare Advantage Claims Data.

PMID- 29459939
TI  - Cognitive Outcomes of Children Born Extremely or Very Preterm Since the 1990s and
      Associated Risk Factors: A Meta-analysis and Meta-regression.
AB  - Importance: Despite apparent progress in perinatal care, children born extremely
      or very preterm (EP/VP) remain at high risk for cognitive deficits. Insight into
      factors contributing to cognitive outcome is key to improve outcomes after EP/VP
      birth. Objective: To examine the cognitive abilities of children of EP/VP birth
      (EP/VP children) and the role of perinatal and demographic risk factors. Data
      Sources: PubMed, Web of Science, and PsycINFO were searched without language
      restriction (last search March 2, 2017). Key search terms included preterm, low
      birth weight, and intelligence. Study Selection: Peer-reviewed studies reporting
      intelligence scores of EP/VP children (<32 weeks of gestation) and full-term
      controls at age 5 years or older, born in the antenatal corticosteroids and
      surfactant era, were included. A total of 268 studies met selection criteria, of
      which 71 covered unique cohorts. Data Extraction and Synthesis: MOOSE guidelines
      were followed. Data were independently extracted by 2 researchers. Standardized
      mean differences in intelligence per study were pooled using random-effects meta
      analysis. Heterogeneity in effect size across studies was studied using
      multivariate, random-effects meta-regression analysis. Main Outcomes and
      Measures: Primary outcome was intelligence. Covariates included gestational age,
      birth weight, birth year, age at assessment, sex, race/ethnicity, socioeconomic
      status, small for gestational age, intraventricular hemorrhage, periventricular
      leukomalacia, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis,
      sepsis, and postnatal corticosteroid use. Results: The 71 included studies
      comprised 7752 EP/VP children and 5155 controls. Median gestational age was 28.5
      weeks (interquartile range [IQR], 2.4 weeks) and the mean age at assessment
      ranged from 5.0 to 20.1 years. The median proportion of males was 50.0% (IQR,
      8.7%). Preterm children had a 0.86-SD lower IQ compared with controls (95% CI, 
      0.94 to -0.78, P < .001). Results were heterogeneous across studies (I2 = 74.13;
      P < .001). This heterogeneity could not be explained by birth year of the cohort.
      Multivariate meta-regression analysis with backward elimination revealed that BPD
      explained 65% of the variance in intelligence across studies, with each percent
      increase in BPD rate across studies associated with a 0.01-SD decrease in IQ
      (0.15 IQ points) (P < .001). Conclusions and Relevance: Extremely or very preterm
      children born in the antenatal corticosteroids and surfactant era show large
      deficits in intelligence. No improvement in cognitive outcome was observed
      between 1990 and 2008. These findings emphasize that improving outcomes after
      EP/VP birth remains a major challenge. Bronchopulmonary dysplasia was found to be
      a crucial factor for cognitive outcome. Lowering the high incidence of BPD may be
      key to improving long-term outcomes after EP/VP birth.

PMID- 29459941
TI  - Functional Outcome After Intracranial Pressure Monitoring.

PMID- 29459942
TI  - Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission
      of Overweight and Obesity From Mother to Offspring.
AB  - Importance: Maternal overweight, which often results in cesarean delivery, is a
      strong risk factor for child overweight. Little is known about the joint
      contribution of birth mode and microbiota in the infant gut to the association
      between maternal prepregnancy overweight and child overweight. Objective: To
      investigate the association of birth mode with microbiota in the infant gut, and
      whether this mediates the association between maternal and child overweight.
      Design, Setting, and Participants: An observational study was conducted of 935
      full-term infants born between January 1, 2009, and December 31, 2012, in the
      Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Maternal
      prepregnancy body mass index (BMI) was calculated as weight in kilograms divided
      by height in meters squared using height and weight data taken from medical
      records or maternal report. Infant gut microbiota were profiled with 16S
      ribosomal RNA sequencing in fecal samples collected at a mean (SD) age of 3.7
      (1.0) months. At ages 1 and 3 years, BMI z scores adjusted for age and sex were
      generated according to World Health Organization criteria. Statistical analysis
      was conducted from January 29 to June 15, 2017. Exposures: Mothers of normal
      weight (BMI, 18.5-24.9) and overweight or obese (BMI, >=25.0) mothers. Main
      Outcome and Measures: Risk of overweight and obesity (>97th percentile BMI z
      scores) among children at ages 1 and 3 years. Results: Of the 935 mother-infant
      pairs in the study (mean [SD] age, 32.5 [4.5] years) 382 (40.9%) were overweight,
      69 of 926 infants (7.5%) were overweight at age 1 year, and 90 of 866 infants
      (10.4%) were overweight at age 3 years. Compared with being born vaginally to a
      mother of normal weight, infants born vaginally to overweight or obese mothers
      were 3 times more likely to become overweight at age 1 year (adjusted odds ratio
      [OR], 3.33; 95% CI, 1.49-7.41), while cesarean-delivered infants of overweight
      mothers had a 5-fold risk of overweight at age 1 year (adjusted OR, 5.02; 95% CI,
      2.04-12.38). Similar risks were also observed at age 3 years. Multiple mediator
      path modeling revealed that birth mode and infant gut microbiota (Firmicutes
      species richness, especially of the Lachnospiraceae family) sequentially mediated
      the association between maternal prepregnancy overweight and childhood overweight
      at ages 1 and 3 years. Bacterial genera belonging to the Lachnospiraceae family
      were more abundant in infants of overweight mothers; however, the participating
      genera of Lachnospiraceae differed between infants delivered vaginally and those
      delivered via cesarean birth. Conclusions and Relevance: This study found
      evidence of a novel sequential mediator pathway involving birth mode and
      Firmicutes species richness (especially higher abundance of Lachnospiraceae) for
      the intergenerational transmission of overweight.

PMID- 29459943
TI  - Association of Epidural Stimulation With Cardiovascular Function in an Individual
      With Spinal Cord Injury.

PMID- 29459944
TI  - Association of Changes in Plasma Neurofilament Light and Tau Levels With
      Anesthesia and Surgery: Results From the CAPACITY and ARCADIAN Studies.
AB  - Importance: Anesthesia and surgery are believed to act on the central nervous
      system by a fully reversible mechanism innocuous to nerve cells. Evidence that
      neurological sequelae may follow would challenge this belief and would thereby
      suggest a need to reassess theories of the mechanism of anesthetic action or the
      response of the central nervous system to surgery. Objective: To measure 2
      biomarkers of neurological injury (neurofilament light and tau) in plasma in a
      series of timed collections before and after anesthesia and surgery. Design,
      Setting, and Participants: These 2 related observational studies (CAPACITY and
      ARCADIAN) recruited patients 60 years and older who were undergoing general
      anesthesia for surgeries performed within a tertiary hospital. Blood samples were
      taken immediately before surgical anesthesia was administered and then
      sequentially after surgery at 30-minute, 6-hour, 24-hour, and 48-hour intervals.
      Sampling took place from January 2014 to August 2015. Data analysis took place
      from October 2016 to February 2017. Main Outcomes and Measures: Plasma
      neurofilament light and tau. Results: A total of 30 patients were enrolled (13
      from the CAPACITY study and 17 from the ARCADIAN study). The mean (SD) age was
      69.1 (7.0) years, and 18 members (59%) of the participant group were female; 22
      (73%) were undergoing joint arthroplasty. Mean neurofilament light increased at
      each measurement from a combined baseline mean (SD) of 22.3 (20.4) pg/mL to a
      maximal combined mean (SD) level of 35.1 (28.7) pg/mL, a maximum increase of 67%
      (95% CI, 45%-89%; P < .001), at 48 hours postoperatively. The level of tau
      increased significantly from baseline at every measurement, from a combined
      baseline mean (SD) of 3.1 (1.3) pg/mL to a maximal combined mean (SD) of 10.8
      (9.5) pg/mL, a peak increase of 257% (95% CI, 154%-361%; P < .001), at 6 hours
      postoperatively. After 6 hours, the mean level began to return to baseline but
      remained elevated after 48 hours. Conclusions and Relevance: Neurofilament light
      is a specific marker of axonal injury and has been shown to indicate neuronal
      damage in a number of diseases. Tau proteins are an integral component of axonal
      integrity, and increased tau indicates neuronal damage. The increases in both
      neurofilament light and tau over 48 hours after surgery suggest that general
      anesthesia and surgery may be associated with neuronal damage in the short term.
      Further investigations will be required to study any association with clinical
      outcomes. These preliminary findings demand that we question the prevailing
      assumption that anesthesia and surgery are innocuous, transient, and without
      injurious changes to the central nervous system.

PMID- 29459945
TI  - Correlates and Outcomes of Physician Burnout Within a Large Academic Medical
      Center.

PMID- 29459946
TI  - Hydroxychloroquine to Reduce Symptoms of Hand Osteoarthritis.

PMID- 29459948
TI  - Can Small Physician Practices Survive?: Sharing Services as a Path to Viability.

PMID- 29459947
TI  - Association of Vegetation Size With Embolic Risk in Patients With Infective
      Endocarditis: A Systematic Review and Meta-analysis.
AB  - Importance: Infective endocarditis is a life-threating condition with annual
      mortality of as much as 40% and is associated with embolic events in as many as
      80% of cases. These embolic events have notable prognostic implications and have
      been linked to increased length of stay in intensive care units and mortality. A
      vegetation size greater than 10 mm has often been suggested as an optimal cutoff
      to estimate the risk of embolism, but the evidence is based largely on small
      observational studies. Objective: To study the association of vegetation size
      greater than 10 mm with embolic events using meta-analytic techniques. Data
      Sources: A computerized literature search of all publications in the PubMed and
      EMBASE databases from inception to May 1, 2017, was performed with search terms
      including varying combinations of infective endocarditis, emboli, vegetation
      size, pulmonary infarct, stroke, splenic emboli, renal emboli, retinal emboli,
      and mesenteric emboli. This search was last assessed as being up to date on May
      1, 2017. Study Selection: Observational studies or randomized clinical trials
      that evaluated the association of vegetation size greater than 10 mm with embolic
      events in adult patients with infective endocarditis were included. Conference
      abstracts and non-English language literature were excluded. The search was
      conducted by 2 independent reviewers blinded to the other's work. Data Extraction
      and Synthesis: Following PRISMA guidelines, the 2 reviewers independently
      extracted data; disputes were resolved with consensus or by a third investigator.
      Categorical dichotomous data were summarized across treatment arms using Mantel
      Haenszel odds ratios (ORs) with 95% CIs. Heterogeneity of effects was evaluated
      using the Higgins I2 statistic. Results: The search yielded 21 unique studies
      published from 1983 to 2016 with a total of 6646 unique patients with infective
      endocarditis and 5116 vegetations with available dimensions. Patients with a
      vegetation size greater than 10 mm had increased odds of embolic events (OR,
      2.28; 95% CI, 1.71-3.05; P < .001) and mortality (OR, 1.63; 95% CI, 1.13-2.35; P
      = .009) compared with those with a vegetation size less than 10 mm. Conclusions
      and Relevance: In this meta-analysis of 21 studies, patients with vegetation size
      greater than 10 mm had significantly increased odds of embolism and mortality.
      Understanding the risk of embolization will allow clinicians to adequately risk
      stratify patients and will also help facilitate discussions regarding surgery in
      patients with a vegetation size greater than 10 mm.

PMID- 29459949
TI  - Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With
      Chronic Myeloid Leukemia in Chronic Phase: Results From a Single-Group, Phase 2,
      Open-Label Study.
AB  - Background: Treatment-free remission (TFR)-that is, stopping tyrosine kinase
      inhibitor (TKI) therapy without loss of response-is an emerging treatment goal in
      chronic myeloid leukemia (CML). Objective: To evaluate TFR after discontinuation
      of second-line nilotinib therapy. Design: Single-group, phase 2, open-label
      study. (ClinicalTrials.gov: NCT01698905). Setting: 63 centers in 18 countries.
      Patients: Adults with CML in chronic phase who received TKI therapy for at least
      3 years (>4 weeks with imatinib, then >=2 years with nilotinib) and achieved
      MR4.5 (BCR-ABL1 <=0.0032% on the International Scale [BCR-ABL1IS]) while
      receiving nilotinib entered a 1-year consolidation phase. Those with sustained
      MR4.5 during consolidation were eligible to enter TFR. Interventions: Patients
      received nilotinib during consolidation; those who entered TFR stopped treatment.
      Patients with loss of major molecular response (MMR) (BCR-ABL1IS <=0.1%) or
      confirmed loss of MR4 (BCR-ABL1IS <=0.01%) during TFR reinitiated nilotinib
      treatment. Measurements: Proportion of patients without loss of MMR, confirmed
      loss of MR4, or treatment reinitiation within 48 weeks of stopping treatment
      (primary end point). Results: 163 patients who had switched from imatinib to
      nilotinib (for reasons including resistance, intolerance, and physician
      preference) enrolled in the study and entered the consolidation phase. Of these
      patients, 126 met the criteria for entering the TFR phase, and 73 (58% [95% CI,
      49% to 67%]) and 67 (53% [CI, 44% to 62%]) maintained TFR at 48 weeks (primary
      end point) and 96 weeks, respectively. Of the 56 patients who reinitiated
      nilotinib therapy, 55 regained MMR or better and 52 regained MR4.5. None had CML
      progression to accelerated phase or blast crisis. Musculoskeletal pain was more
      frequent during the first 48 weeks after nilotinib discontinuation. Limitation:
      The study included a heterogeneous patient population and was not designed to
      compare outcomes between patients continuing and those stopping treatment.
      Conclusion: TFR seems achievable in patients with sustained MR4.5 after switching
      to nilotinib. Primary Funding Source: Novartis Pharmaceuticals Corporation.

PMID- 29459950
TI  - Functional Outcome After Intracranial Presuure Monitoring-Reply.

PMID- 29459951
TI  - Guideline: Recommendations are provided for antiretroviral therapies in pregnant
      women with HIV.

PMID- 29459952
TI  - Review: In primary prevention, BP-lowering treatment reduces major CV events in
      patients with SBP >= 140 mm Hg.

PMID- 29459953
TI  - Review: In hypertension, BP self-monitoring interventions improve BP levels and
      BP control at 12 months.

PMID- 29459954
TI  - Late thrombectomy reduced disability in acute stroke with mismatched clinical
      deficit and infarction volume.

PMID- 29459955
TI  - Review: DOACs reduce intracranial hemorrhage more than warfarin in AF with CKD.

PMID- 29459956
TI  - Review: Procalcitonin-guided starting and stopping of antibiotics in acute
      respiratory infections reduces mortality.

PMID- 29459957
TI  - In suspected OSA, home respiratory polygraphy was noninferior to polysomnography
      for reducing symptoms.

PMID- 29459958
TI  - Ibuprofen + acetaminophen did not differ from opioids + acetaminophen for
      reducing acute extremity pain at 2 h.

PMID- 29459959
TI  - Sodium bicarb vs sodium chloride, and acetylcysteine vs placebo, did not differ
      for adverse events after angiography.

PMID- 29459960
TI  - In patients with rheumatoid arthritis, bDMARD therapy was not associated with
      malignant neoplasms.

PMID- 29459961
TI  - Osteoporosis.

PMID- 29459963
TI  - Increasing Incidence of Multiply Recurrent Clostridium difficile Infection.

PMID- 29459964
TI  - Increasing Incidence of Multiply Recurrent Clostridium difficile Infection.

PMID- 29459962
TI  - Osteoporosis.

PMID- 29459965
TI  - Increasing Incidence of Multiply Recurrent Clostridium difficile Infection.

PMID- 29459966
TI  - Hyperammonemia After Blood Transfusion.

PMID- 29459967
TI  - Hyperammonemia After Blood Transfusion.

PMID- 29459969
TI  - Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study.

PMID- 29459968
TI  - Hyperammonemia After Blood Transfusion.

PMID- 29459970
TI  - Politics and Professionalism.

PMID- 29459971
TI  - Shouldering.

PMID- 29459973
TI  - Annals for Educators - 20 February 2018.

PMID- 29459972
TI  - Web Exclusives. Annals for Hospitalists Inpatient Notes - Perioperative Medicine
      The Past, Present, and Future of Cardiovascular Risk Assessment and Risk
      Reduction Strategies.

PMID- 29459974
TI  - Annals for Hospitalists - 20 February 2018.

PMID- 29459975
TI  - The Health Consequences of Natural Disasters in the United States: Progress,
      Perils, and Opportunity.

PMID- 29459976
TI  - Restoring Order to Postoperative Neurocognitive Disorders.

PMID- 29459977
TI  - Evidence Underpinning the Centers for Medicare & Medicaid Services' Severe Sepsis
      and Septic Shock Management Bundle (SEP-1): A Systematic Review.
AB  - : This article has been corrected. To see what has changed, please read the
      Letter to the Editor and the authors' response. The original version (PDF) is
      appended to this article as a Supplement. Background: The Severe Sepsis and
      Septic Shock Early Management Bundle (SEP-1), the sepsis performance measure
      introduced in 2015 by the Centers for Medicare & Medicaid Services (CMS),
      requires the reporting of up to 5 hemodynamic interventions, as many as 141
      tasks, and 3 hours to document for a single patient. Purpose: To evaluate whether
      moderate- or high-level evidence shows that use of the 2015 SEP-1 or its
      hemodynamic interventions improves survival in adults with sepsis. Data Sources:
      PubMed, Embase, Scopus, Web of Science, and ClinicalTrials.gov from inception to
      28 November 2017 with no language restrictions. Study Selection: Randomized and
      observational studies of death among adults with sepsis who received versus those
      who did not receive either the entire SEP-1 bundle or 1 or more SEP-1 hemodynamic
      interventions, including serial lactate measurements; a fluid infusion of 30
      mL/kg of body weight; and assessment of volume status and tissue perfusion with a
      focused examination, bedside cardiovascular ultrasonography, or fluid
      responsiveness testing. Data Extraction: Two investigators independently
      extracted study data and assessed each study's risk of bias; 4 authors rated
      level of evidence by consensus using CMS criteria published in 2013. High- or
      moderate-level evidence required studies to have no confounders and low risk of
      bias. Data Synthesis: Of 56 563 references, 20 studies (18 reports) met inclusion
      criteria. One single-center observational study reported lower in-hospital
      mortality after implementation of the SEP-1 bundle. Sixteen studies (2 randomized
      and 14 observational) reported increased survival with serial lactate
      measurements or 30-mL/kg fluid infusions. None of the 17 studies were free of
      confounders or at low risk of bias. In 3 randomized trials, fluid responsiveness
      testing did not alter survival. Limitations: Few trials, poor-quality and
      confounded studies, and no studies (with survival outcomes) of the focused
      examination or bedside cardiovascular ultrasonography. Use of the 2015 version of
      SEP-1 and 2013 version of CMS evidence criteria, both of which were updated in
      2017. Conclusion: No high- or moderate-level evidence shows that SEP-1 or its
      hemodynamic interventions improve survival in adults with sepsis. Primary Funding
      Source: National Institutes of Health. (PROSPERO: CRD42016052716).

PMID- 29459978
TI  - Patient-Centered Prescription Opioid Tapering in Community Outpatients With
      Chronic Pain.

PMID- 29459979
TI  - Infant Mortality Due to Unintentional Suffocation Among Infants Younger Than 1
      Year in the United States, 1999-2015.

PMID- 29459980
TI  - Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease
      Mineral and Bone Disorder: Synopsis of the Kidney Disease: Improving Global
      Outcomes 2017 Clinical Practice Guideline Update.
AB  - Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 Clinical
      Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and
      Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a
      selective update of the prior CKD-MBD guideline published in 2009. The guideline
      update and the original publication are intended to assist practitioners caring
      for adults with CKD and those receiving long-term dialysis. Methods: Development
      of the guideline update followed an explicit process of evidence review and
      appraisal. The approach adopted by the Work Group and the evidence review team
      was based on systematic reviews of relevant trials, appraisal of the quality of
      the evidence, and rating of the strength of recommendations according to the
      GRADE (Grading of Recommendations Assessment, Development and Evaluation)
      approach. Searches of the English-language literature were conducted through
      September 2015 and were supplemented with targeted searches through February
      2017. Final modification of the guidelines was informed by a public review
      process involving numerous stakeholders, including patients, subject matter
      experts, and industry and national organizations. Recommendations: The update
      process resulted in the revision of 15 recommendations. This synopsis focuses
      primarily on recommendations for diagnosis of and testing for CKD-MBD and
      treatment of CKD-MBD that emphasizes decreasing phosphate levels, maintaining
      calcium levels, and addressing elevated parathyroid hormone levels in adults with
      CKD stage G3a to G5 and those receiving dialysis. Key elements include basing
      treatment on trends in laboratory values rather than a single abnormal result and
      being cautious to avoid hypercalcemia when treating secondary
      hyperparathyroidism.

PMID- 29459981
TI  - Association Between Prenatal Valproate Exposure and Performance on Standardized
      Language and Mathematics Tests in School-aged Children.
AB  - Importance: Valproate sodium is used for the treatment of epilepsy and other
      neuropsychiatric disorders in women of childbearing potential. However, there are
      concerns about impaired cognitive development in children who have been exposed
      to valproate during pregnancy. Objective: To estimate the association between
      long-term school performance and prenatal exposure to valproate and a number of
      other antiepileptic drugs (AEDs). Design, Setting, and Participants: In a
      prospective, population-based cohort study conducted from August 1, 2015, to May
      31, 2017, data used in the study were provided by Statistics Denmark on April 15,
      2016. All children born alive in Denmark between 1997 and 2006 (n = 656 496) were
      identified. From this cohort, children who did not participate in the national
      tests, with presumed coding errors in gestational age and children missing
      information on their mother's educational level or household income were excluded
      (n = 177 469) leaving 479 027 children for the analyses. Children were identified
      and linked across national registers that had information on exposure,
      covariates, and outcome. The primary outcome was performance in national tests,
      an academic test taken by students in Danish primary and lower secondary state
      schools. We assessed performance in Danish and mathematics at different grades
      among valproate-exposed children and compared their performance with that of
      unexposed children and children exposed to another AED (lamotrigine). Test scores
      were standardized to z scores and adjusted for risk factors. Main Outcome and
      Measures: Difference in standardized z scores in Danish and mathematics tests
      among valproate-exposed children compared with unexposed and lamotrigine-exposed
      children. Results: Of the 656 496 children identified, 479 027 children who
      participated in the national tests were evaluated, including children exposed to
      the following AEDs in monotherapy: valproate, 253; phenobarbital, 86;
      oxcarbazepine, 236; lamotrigine, 396; clonazepam, 188; and carbamazepine, 294.
      The mean (SD) age of the 244 095 children completing the sixth-grade Danish test
      was 12.9 (0.39) years; 122 774 (50.3%; 95% CI, 50.1% to 50.5%) were boys and 121
      321 (49.7%; 95% CI, 49.5% to 49.9%) were girls. Valproate-exposed children scored
      worse on the sixth-grade Danish tests (adjusted difference, -0.27 SD; 95% CI, 
      0.42 to -0.12) and sixth-grade mathematics tests (adjusted difference, -0.33 SD;
      (95% CI, -0.47 to -0.19) compared with unexposed children and children exposed to
      lamotrigine (adjusted difference, -0.33 SD; 95% CI, -0.60 to -0.06). Also,
      children exposed to clonazepam scored worse in the sixth-grade Danish tests
      (adjusted difference, -0.07 SD; 95% CI, -0.12 to -0.02). Carbamazepine,
      lamotrigine, phenobarbital, and oxcarbazepine were not linked to poor school
      performance compared with unexposed children. Conclusions and Relevance: Maternal
      use of valproate was associated with a significant decrease in school performance
      in offspring compared with children unexposed to AEDs and children exposed to
      lamotrigine. Findings of this study further caution against the use of valproate
      among women of childbearing potential.

PMID- 29459982
TI  - Defining Pediatric Sepsis.

PMID- 29459983
TI  - Does More Achievement Make Us Better Physicians?: The Academic Arms Race.

PMID- 29459984
TI  - Hydroxychloroquine: Another Battle Lost in the Campaign to Find Effective
      Therapies for Hand Osteoarthritis.

PMID- 29459985
TI  - When Do alpha-Synucleinopathies Start? An Epidemiological Timeline: A Review.
AB  - Importance: This article reviews the epidemiological evidence of features of
      alpha-synucleinopathies that precede clinical onset of disease, proposes a
      clinical timeline, and attempts to define the different premotor and clinical
      phenotypes associated with alpha-synucleinopathies. Observations: The
      pathological hallmarks of the alpha-synucleinopathies (Parkinson disease,
      Parkinson disease dementia, dementia with Lewy bodies, and multisystem atrophy)
      begin years before a clinical diagnosis. Epidemiologic studies support the long
      gap between pathology and symptoms and suggest that certain nonmotor conditions
      (constipation, anxiety, and rapid eye movement sleep behavior disorder) precede
      the traditional motor Parkinson disease phenotype by long intervals. Conclusions
      and Relevance: Characterizing the temporal onset of these conditions will help to
      better recognize the premotor phase of the alpha-synucleinopathies and specific
      clinical phenotypes and will guide the search for predictive biomarkers and risk
      or protective factors for Parkinson disease and other synucleinopathies.

PMID- 29459987
TI  - Immune-Mediated Necrotizing Myopathy and Dietary Sources of Statins.

PMID- 29459986
TI  - Hydroxychloroquine Effectiveness in Reducing Symptoms of Hand Osteoarthritis: A
      Randomized Trial.
AB  - Background: Synovitis is believed to play a role in producing symptoms in persons
      with hand osteoarthritis, but data on slow-acting anti-inflammatory treatments
      are sparse. Objective: To determine the effectiveness of hydroxychloroquine
      versus placebo as an analgesic treatment of hand osteoarthritis. Design:
      Randomized, double-blind, placebo-controlled clinical trial with 12-month follow
      up. (ISRCTN registry number: ISRCTN91859104). Setting: 13 primary and secondary
      care centers in England. Participants: Of 316 patients screened, 248 participants
      (82% women; mean age, 62.7 years) with symptomatic (pain >=4 on a 0- to 10-point
      visual analogue scale) and radiographic hand osteoarthritis were randomly
      assigned and 210 (84.7%) completed the 6-month primary end point. Intervention:
      Hydroxychloroquine (200 to 400 mg) or placebo (1:1) for 12 months with ongoing
      usual care. Measurements: The primary end point was average hand pain during the
      previous 2 weeks (on a 0- to 10-point numerical rating scale [NRS]) at 6 months.
      Secondary end points included self-reported pain and function, grip strength,
      quality of life, radiographic structural change, and adverse events. Baseline
      ultrasonography was done. Results: At 6 months, mean hand pain was 5.49 points in
      the placebo group and 5.66 points in the hydroxychloroquine group, with a
      treatment difference of -0.16 point (95% CI, -0.73 to 0.40 point) (P = 0.57).
      Results were robust to adjustments for adherence, missing data, and use of rescue
      medication. No significant treatment differences existed at 3, 6, or 12 months
      for any secondary outcomes. The percentage of participants with at least 1 joint
      with synovitis was 94% (134 of 143) on grayscale ultrasonography and 59% on power
      Doppler. Baseline structural damage or synovitis did not affect treatment
      response. Fifteen serious adverse events were reported (7 in the
      hydroxychloroquine group [3 defined as possibly related] and 8 in the placebo
      group). Limitation: Hydroxychloroquine dosage restrictions may have reduced
      efficacy. Conclusion: Hydroxychloroquine was no more effective than placebo for
      pain relief in patients with moderate to severe hand pain and radiographic
      osteoarthritis. Primary Funding Source: Arthritis Research UK.

PMID- 29459988
TI  - Lifetime prevalence and age-of-onset of mental disorders in adults from the
      Argentinean Study of Mental Health Epidemiology.
AB  - PURPOSE: Although the Global Burden of Disease Study estimated that depressive
      disorders and anxiety disorders are the second and fifth leading causes of
      disability in Argentina, these estimates were based on imputations rather than
      epidemiological data. The policy implications of these results for the necessary
      expansion of mental health services in Argentina are sufficiently great that more
      direct estimates of the population burdens of common mental disorders are needed.
      Therefore, the purpose is to present the first results regarding lifetime
      prevalence, projected lifetime risk up to age 75, age-of-onset, cohort effects
      and socio-demographic correlates of DSM-IV mental disorders among adults (18+)
      from the general population of urban areas of Argentina. METHOD: A multistage
      clustered area probability household survey was administered to 3927 individuals
      using the World Mental Health Composite International Diagnostic Interview.
      RESULTS: Lifetime prevalence of any disorder was 29.1% and projected lifetime
      risk at age 75 was 37.1%. Median age-of-onset of any disorder was 20 years of
      age. Disorders with highest lifetime prevalence were major depressive disorder
      (8.7%), alcohol abuse (8.1%), and specific phobia (6.8%). Anxiety disorders were
      the most prevalent group of disorder (16.4%) followed by mood (12.3%), substance
      (10.4%), and disruptive behavior disorders (2.5%). Women had greater odds of
      anxiety and mood disorders; men had greater odds of substance disorders. Age-at
      interview was inversely associated with lifetime risk of any disorder.
      DISCUSSION: The results provide direct evidence for high lifetime societal
      burdens of common mental disorders in Argentina due to a combination of high
      prevalence and early age-of-onset.

PMID- 29459989
TI  - [Cognition and mobility : The influence of the brain on gait].
AB  - Cognitive abilities and gait with its physical parameters are important for
      mobility. There is clinically sound evidence that a reduction of gait speed can
      be seen as an early subclinical indicator of cognitive decline of even higher
      risk of onset of dementia. The dual-task paradigm is a method in which the older
      person has to simultaneously solve two different task. It is of utmost importance
      to identify older persons at risk of falls or onset of dementia. The dual-task
      paradigm seems to be an important method in this process.

PMID- 29459990
TI  - [Acute treatment and secondary prophylaxis of ischemic stroke : An excellent
      example for personalized medicine].
AB  - About a quarter of a million people in Germany suffer a stroke every year. Stroke
      is the most dreaded cardiovascular disease, even before myocardial infarction and
      heart failure. In the last two to three years, significant progress has been made
      in acute treatment, secondary prophylaxis in patients with patent foramen ovale,
      and the interdisciplinary evaluation of atrial fibrillation as the cause of the
      stroke. These new findings allow for more precise treatment.

PMID- 29459991
TI  - [Infectious diseases - a specialty of internal medicine].
AB  - Infectious diseases have recently gained wide public interest. Emerging
      infections and rising rates of antibiotic resistance are determining this trend.
      Both challenges will need to be addressed in international and local
      collaborations between different specialties in medicine and basic science.
      Infectious diseases as a clinical specialty in this scenario is directly
      responsible for the care of patients with infectious diseases. Its involvement in
      the care of patients with complicated infections has proved to be highly
      effective. Antibiotic stewardship programmes are effective measures in slowing
      the development of antibiotic resistance and have been widely implemented. But
      antibiotic stewardship specialists should not be confused with or taken as an
      alternative to infectious disease experts. Infectious diseases requires
      appropriate and specific training. It mainly uses the instrumentarium of internal
      medicine. With the current challenges in modern medicine, infectious diseases in
      Germany should thus be upgraded from a subspecialty to a clinical specialty,
      ideally within Internal Medicine.

PMID- 29459993
TI  - Proposal for an extended pTNM classification of thyroid carcinoma : Commentary on
      deficits of the 8th edition of the TNM classification.
AB  - In the 8th edition of the TNM classification of thyroid carcinomas, which was
      introduced in 2017, carcinomas with minimal extrathyroidal extension are no
      longer mentioned, which might cause problems. These tumors were explicitly
      categorized in previous TNM classifications (5-7th editions). Studies on the
      prognostic relevance of minimal extrathyroidal extension have shown conflicting
      results. Moreover, the vast majority of these studies retrospectively analyzed
      only subgroups of thyroid carcinomas (e.g. differentiated thyroid carcinoma,
      papillary thyroid carcinoma). The proposed subcategorization of the current TNM
      classification (8th edition) ensures the continuity of the parameter minimal
      extrathyroidal extension within the TNM categorization of thyroid carcinomas and
      also offers the possibility to prospectively analyze in a standardized manner the
      potential biological relevance of minimal extrathyroidal extension in relation to
      tumor categories (T/pT category).

PMID- 29459992
TI  - A systematic classification of the vertebral artery variable origin: clinical and
      surgical implications.
AB  - Several congenital anomalies regarding the right (RVA) and left (LVA) vertebral
      artery have been described. The current paper aims to perform a systematic
      literature review of the variable vertebral artery (VA) origin from the aortic
      arch (AOA) and its branches. The incidence of these variants and the ensuing AOA
      branching pattern are highlighted. Atypical origin cases were found more commonly
      unilaterally, while LVA presented the majority of the aberrancies. The LVA
      emersion from the AOA (3.6%) and the RVA from the right common carotid artery
      (RCCA) (0.14%) were the commonest origin variations. Aberrant RVA origin as last
      branch of the AOA is very rare. Eighteen cases (0.12%) with an aberrant right
      subclavian artery (ARSCA) were found. Among them, the RVA originated from the
      RCCA and right subclavian artery in 94.4 and 5.6%, respectively. Sporadic cases
      had an AOA origin bilaterally; RVA and LVA had a double origin in 0.027 and
      0.11%, respectively. A dual origin was detected in 0.0069%, bilaterally. The
      atypical VA origin may coexist with: (i) an ARSCA, (ii) a common origin of
      brachiocephalic artery and left common carotid artery (the misnomer bovine arch)
      and (iii) a bicarotid trunk. The aberrant VA origin favors hemodynamic
      alterations, predisposing to cerebrovascular disorders and intracranial aneurysm
      formation. Detailed information of VA variants is crucial for both endovascular
      interventionists and diagnostic radiologists involved in the treatment of
      patients with cerebrovascular disease. Such information may prove useful to
      minimize the risk of VA injury in several procedures.

PMID- 29459994
TI  - Dual-centre randomized-controlled trial comparing transurethral endoscopic
      enucleation of the prostate using diode laser vs. bipolar plasmakinetic for the
      treatment of LUTS secondary of benign prostate obstruction: 1-year follow-up
      results.
AB  - PURPOSE: Bipolar endoscopic enucleation of the prostate (BEEP) was recommended by
      the 2016 EAU guidelines as the first choice of surgical treatment in men with a
      substantially enlarged prostate and moderate-to-severe lower urinary tract
      symptoms. The main aim of this study was to compare a modified diode laser
      enucleation of the prostate (DiLEP) to BEEP. METHODS: A total of 114 patients
      with prostate (20-160 mL) were randomized 1:1 into either DiLEP or BEEP in a dual
      centre, non-inferiority-design randomized-controlled trial. The primary outcomes
      included Qmax and IPSS at 12 months. Non-inferiority was evaluated by comparing
      the two-sided 95% CI for the mean differences of Qmax and IPSS. Secondary
      endpoints included other perioperative parameters, postoperative micturition
      variables, and complication rate. RESULTS: A total of 111 patients (97%) had
      completed the intent-to-treat analysis, The results showed that DiLEP was
      comparable to BEEP regarding Qmax (28.0 +/- 7.0 vs. 28.1 +/- 7.2 mL/s) and IPSS
      (3.0 +/- 2.2 vs. 2.9 +/- 2.6) at 12 months, the non-inferiority was met for both
      Qmax and IPSS. There were also no significant difference between two groups
      regarding tissue removal rate (71.8 vs. 73.8%), hemoglobin decrease (0.33 +/-
      0.66 vs. 0.36 +/- 0.75 g/dL), sodium decrease (1.0 +/- 2.7 vs. 0.3 +/- 2.9
      mmol/L), and Clavien III complications (5.3 vs. 1.8%) at 12 months. CONCLUSIONS:
      This DiLEP is an anatomical endoscopic enucleation technique for the treatment of
      benign prostatic hyperplasia, it is non-inferior to BEEP regarding Qmax and IPSS
      at 12 months postoperatively.

PMID- 29459995
TI  - Reflections on personalized management of UTUC.

PMID- 29459996
TI  - Robotic surgery in public hospitals of Latin-America: a castle of sand?
AB  - INTRODUCTION: There is no information about the evolution of robotic programs in
      public hospitals of Latin-America. OBJECTIVE: To describe the current status and
      functioning of robotic programs in Latin-American public hospitals since their
      beginning to date. METHODS: We conducted a survey among leading urologists
      working at public hospitals of Latin-America who had acquired the Da Vinci
      laparoscopic-assisted robotic system. Questions included: date the program
      started, its utilization by other services, number and kind of surgeries, surgery
      paying system, surgery related deaths, occurrence and reasons of robotic program
      interruptions and its use for training purposes. Medians and 25-75 centiles (IQR)
      were estimated. RESULTS: Since 2009, there are ten public hospitals of four Latin
      American countries that acquired the Da Vinci robotic system. The median number
      of months robotic programs has been functioning without considering transitory
      interruption: 43 (IQR 35, 55). Median number of urologic and total surgeries
      performed: 140 (IQR 94, 168) and 336 (IQR 292, 621), respectively. The
      corresponding median number of urologic and total surgeries performed per month:
      3 (IQR 2, 5) and 8 (IQR 5, 11). Median number of total surgeries performed per
      year per institution was 94 (IQR 68,123). The median proportion of urologic cases
      was 40% (IQR 31, 48), ranging from 24 to 66%. Five of ten institutions had their
      urology programs transitory or definitively closed due to the high burden costs.
      CONCLUSION: Adoption and development of robotic surgery in some public hospitals
      of Latin-America have been hindered by high costs.

PMID- 29459997
TI  - The effects of intra-arterial chemotherapy on bladder preservation in patients
      with T1 stage bladder cancer.
AB  - PURPOSE: To investigate the effects of intra-arterial chemotherapy on T1 stage
      bladder cancer (Bca) and evaluate patient outcome with bladder-preserving
      treatment approaches. MATERIALS AND METHODS: A total of 238 patients with T1
      stage Bca were retrospectively analyzed. Among them, 35 patients were categorized
      into the subgroup of highest-risk T1 stage according to the European Association
      of Urology guidelines and received immediate radical cystectomy (RC group),
      whereas 62 were classified as being highest-risk T1 patients but were unwilling
      to undergo RC and were treated with gemcitabine plus cisplatin intra-arterial
      chemotherapy (GC group). There were 141 T1 patients who had bladder-preserving
      surgery with intravesical chemotherapy (IVC group). RESULTS: For patients with T1
      stage Bca, the GC group had a higher estimated recurrence-free survival rate
      (44.4 vs. 13.9%, P = 0.087), progression-free survival rate (75.4 vs. 32.8%, P =
      0.006), and cancer-specific survival (CSS) rate (78.7 vs. 67.5%, P = 0.399) when
      compared with the IVC group, respectively. Using the multivariable regression
      model, the GC intra-arterial chemotherapy was significantly related to bladder
      preservation (P = 0.004), lower recurrence (P = 0.012), and less progression (P =
      0.004). For patients with the highest-risk T1 stage, GC group did not have a
      poorer CSS rate in comparison with the RC group (P = 0.383). Moreover, immediate
      RC did not confer a survival benefit in terms of CSS when compared with those who
      underwent deferred RC after failing GC intra-arterial chemotherapy (P = 0.283).
      CONCLUSIONS: Gemcitabine plus cisplatin intra-arterial chemotherapy may be an
      effective bladder-preserving alternative adjuvant treatment for patients with T1
      stage Bca with oncologic benefits, good compliance, and low toxicity.

PMID- 29459998
TI  - Posterior-stabilized inserts are preferable to cruciate-substituting
      ultracongruent inserts due to more favourable kinematics and stability.
AB  - PURPOSE: It is unknown whether the conforming superiority of ultracongruent (UC)
      inserts over posterior stabilized (PS) inserts, due to an increased anterior lip
      for prevention of anterior displacement of the condyles during knee flexion,
      leads to better knee scores or greater knee stability in arthroplasty patients.
      This meta-analysis compared clinical outcomes, intraoperative kinematics,
      sagittal stability, and range of motion (ROM) between groups with either UC or PS
      inserts in primary total knee arthroplasty (TKA). METHODS: Studies that recorded
      clinical outcomes, intraoperative kinematics, sagittal stability, and ROM in
      patients who underwent primary TKA with UC or PS inserts were included in the
      meta-analysis. Subgroup analyses based on differences in flexion angles were
      performed for intraoperative kinematics. RESULTS: Thirteen studies met the
      criteria for inclusion in the meta-analysis. The UC and PS insert groups reported
      similar pain scores (95% CI - 0.15 to 0.16; n.s.) and function scores (95% CI -
      0.30 to 0.14; n.s.). In contrast, femoral rotation during flexion (95% CI - 0.06
      to 6.35; p = 0.05), posterior femoral translation during flexion (95% CI - 2.74
      to - 0.15; p = 0.03), tibial sagittal laxity at 90 degrees  (95% CI 2.91 to 7.72;
      p < 0.0001), and ROM (95% CI - 4.84 to - 1.53; p = 0.0002) differed significantly
      between the groups. Subgroup analyses revealed that the pooled data for femoral
      rotation were significantly different between groups: 60 degrees , 4.09 (p <
      0.00001); 90 degrees , 7.94 (p < 0.00001); and 120 degrees , 8.16 (p < 0.00001).
      Furthermore, pooled data for posterior femoral translation were significantly
      different between groups: 90 degrees , - 3.70 (p < 0.00001); and 120 degrees , -
      3.96 (p < 0.00001). CONCLUSIONS: There were no significant differences in
      clinical outcomes between the groups with UC and PS inserts. However, the UC
      insert group showed significantly greater external femoral rotation, less
      posterior femoral translation, greater tibial laxity in the sagittal plane, and
      less ROM than the PS insert group. Based on the results of the current meta
      analysis, in substituting the PCL, PS inserts are preferable to UC inserts due to
      more favourable kinematics and stability, even though both inserts have
      equivalent clinical outcomes. LEVEL OF EVIDENCE: Therapeutic study, Level II.

PMID- 29459999
TI  - Bioenergy production from sweet sorghum stalks via a biorefinery perspective.
AB  - Besides free sugars, sweet sorghum stalks contain cellulose and hemicellulose
      that can be used for biofuel production. The pretreatment of stalks without the
      extraction of free sugars is more complicated than typical lignocelluloses,
      because of the degradation of free sugars during most pretreatment processes. In
      this study, the bioconversion of sweet sorghum stalks into biogas and bioethanol
      was studied using an improved organosolv pretreatment within a biorefinery
      framework. The organosolv pretreatment was developed using an aqueous solution of
      ethanol (EtOH) and isopropanol (IPOH). The process was optimized to obtain a
      liquor containing free sugars with the least sugar degradations together with a
      highly degradable solid fraction. The liquor was subjected to anaerobic digestion
      for biomethane production, while the solid was used for ethanol production via
      simultaneous saccharification and fermentation (SSF). The most influencing
      pretreatment parameters, i.e., temperature, time, alcohol to water ratio, EtOH to
      IPOH ratio, and the presence or absence of sulfuric acid (as a catalyst), were
      adjusted to achieve the highest yields of bioconversion. The maximum methane and
      ethanol production yields of 271.2 mL CH4/g VS and 87.8% (equal to the gasoline
      equivalent of 0.170 and 0.241 L/kg, respectively) were achieved from the liquor
      and pretreated solid, respectively; however, they were obtained at different
      optimum conditions. Considering the biorefinery perspective, the highest gasoline
      equivalent of 0.249 L/kg was efficiently obtained from the whole process after
      pretreatment at 140  degrees C for 30 min using 60:20 EtOH/IPOH ratio in the
      presence of 1% sulfuric acid. Further analyses, including enzymatic
      adsorption/desorption, compositional analysis, FTIR, and SEM, were conducted to
      investigate the effects of this newly developed pretreatment on the substrate.

PMID- 29460000
TI  - Biotechnical production of trehalose through the trehalose synthase pathway:
      current status and future prospects.
AB  - Trehalose (alpha-D-glucopyranosyl-(1 -> 1)-alpha-D-glucopyranoside) is a non
      reducing disaccharide composed of two glucose molecules linked by an alpha,alpha
      1,1-glycosidic bond. It possesses physicochemical properties, which account for
      its biological roles in a variety of prokaryotic and eukaryotic organisms and
      invertebrates. Intensive studies of trehalose gradually uncovered its functions,
      and its applications in foods, cosmetics, and pharmaceuticals have increased
      every year. Currently, trehalose is industrially produced by the two-enzyme
      method, which was first developed in 1995 using maltooligosyltrehalose synthase
      (EC 5.4.99.15) and subsequently using maltooligosyltrehalose trehalohydrolase (EC
      3.2.1.141), with starch as the substrate. This biotechnical method has lowered
      the price of trehalose and expanded its applications. However, when trehalose
      synthase (EC 5.4.99.16) was later discovered, this method for trehalose
      production using maltose as the substrate soon became a popular topic because of
      its simplicity and potential in industrial production. Since then, many trehalose
      synthases have been studied. This review summarizes the sources and
      characteristics of reported trehalose synthases, and the most recent advances on
      structural analysis of trehalose synthase, catalytic mechanism, molecular
      modification, and usage in industrial production processes.

PMID- 29460001
TI  - Detection and discrimination of five E. coli pathotypes using a combinatory
      SYBR(r) Green qPCR screening system.
AB  - A detection and discrimination system for five Escherichia coli pathotypes, based
      on a combination of 13 SYBR(r) Green qPCR, has been developed, i.e., combinatory
      SYBR(r) Green qPCR screening system for pathogenic E. coli (CoSYPS Path E. coli).
      It allows the discrimination on isolates and the screening of potential presence
      in food of the following pathotypes of E. coli: shigatoxigenic (STEC) (including
      enterohemorrhagic (EHEC)), enteropathogenic (EPEC), enteroaggregative (EAggEC),
      enteroaggregative shigatoxigenic (EAggSTEC), and enteroinvasive (EIEC) E. coli.
      The SYBR(r) Green qPCR assays target the uidA, ipaH, eae, aggR, aaiC, stx1, and
      stx2 genes. uidA controls for E. coli presence and all the other genes are
      specific targets of E. coli pathotypes. For each gene, two primer pairs have been
      designed to guarantee a sufficient detection even in case of deletion or
      polymorphisms in the target gene. Moreover, all the qPCR have been designed to be
      run together in a single analytical PCR plate. This study includes the primer
      pairs' design, in silico and in situ selectivity, sensitivity, repeatability, and
      reproducibility evaluation of the 13 SYBR(r) Green qPCR assays. Each target
      displayed a selectivity of 100%. The limit of detection of the 13 assays is
      between 1 and 10 genomic copies. Their repeatability and reproducibility comply
      with the European requirements. As a preliminary feasibility study on food, the
      CoSYPS Path E. coli system was subsequently evaluated on four food matrices
      artificially contaminated with pathogenic E. coli. It allowed the detection of an
      initial contamination level as low as 2 to 7 cfu of STEC/25 g of food matrix
      after 24 h of enrichment.

PMID- 29460002
TI  - Expression of trans-membrane serine protease 3 (TMPRSS3) in the human organ of
      Corti.
AB  - TMPRSS3 (Trans-membrane Serine Protease 3) is a type II trans-membrane serine
      protease that has proteolytic activity essential for hearing. Mutations in the
      gene cause non-syndromic autosomal recessive deafness (DFNB8/10) in humans.
      Knowledge about its cellular distribution in the human inner ear may increase our
      understanding of its physiological role and involvement in deafness, ultimately
      leading to therapeutic interventions. In this study, we used super-resolution
      structured illumination microscopy for the first time together with transmission
      electron microscopy to localize the TMPRSS3 protein in the human organ of Corti.
      Archival human cochleae were dissected out during petroclival meningioma surgery.
      Microscopy with Zeiss LSM710 microscope achieved a lateral resolution of
      approximately 80 nm. TMPRSS3 was found to be associated with actin in both inner
      and outer hair cells. TMPRSS3 was located in cell surface-associated cytoskeletal
      bodies (surfoskelosomes) in inner and outer pillar cells and Deiters cells and in
      subcuticular organelles in outer hair cells. Our results suggest that TMPRSS3
      proteolysis is linked to hair cell sterociliary mechanics and to the
      actin/microtubule networks that support cell motility and integrity.

PMID- 29460003
TI  - Detection and phylogenetic analysis of a new adenoviral polymerase gene in
      reptiles in Korea.
AB  - Over a period of 7 years (2004-2011), samples from 34 diseased reptiles provided
      by local governments, zoos, and pet shops were tested for viral infection.
      Animals were diagnosed based on clinical signs, including loss of appetite,
      diarrhea, rhinorrhea, and unexpected sudden death. Most of the exotic animals had
      gastrointestinal problems, such as mucosal redness and ulcers, while the native
      animals had no clinical symptoms. Viral sequences were found in seven animals.
      Retroviral genes were amplified from samples from five Burmese pythons (Python
      molurus bivittatus), an adenovirus was detected in a panther chameleon (Furcifer
      pardalis), and an adenovirus and a paramyxovirus were detected in a tropical
      girdled lizard (Cordylus tropidosternum). Phylogenetic analysis of retroviruses
      and paramyxoviruses showed the highest sequence identity to both a Python molurus
      endogenous retrovirus and a Python curtus endogenous retrovirus and to a lizard
      isolate, respectively. Partial sequencing of an adenoviral DNA polymerase gene
      from the lizard isolate suggested that the corresponding virus was a novel
      isolate different from the reference strain (accession no. AY576677.1). The virus
      was not isolated but was detected, using molecular genetic techniques, in a
      lizard raised in a pet shop. This animal was also coinfected with a
      paramyxovirus.

PMID- 29460004
TI  - The significance of OLGA and OLGIM staging systems in the risk assessment of
      gastric cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Despite extensive research on the criteria for the assessment of
      gastric cancer risk using the Operative Link on Gastritis Assessment (OLGA) and
      Operative Link on Gastritis/Intestinal-Metaplasia Assessment (OLGIM) systems, no
      comprehensive overview or systematic summary on their use is currently available.
      AIM: To perform a systematic review and meta-analysis to assess the efficacy of
      the OLGA and OLGIM staging systems in evaluating gastric cancer risk. METHODS: We
      searched various databases, including PubMed, EMBASE, Medline, and Cochrane's
      library, for articles published before March 2017 on the association between
      OLGA/OLGIM stages and risk of gastric cancer. Statistical analysis was performed
      using RevMan 5.30 and Stata 14.0, with the odds ratio, risk ratio, and 95%
      confidence interval as the effect measures. RESULTS: A meta-analysis of six case
      control studies and two cohort studies, comprising 2700 subjects, was performed.
      The meta-analysis of prospective case-control studies demonstrated a significant
      association between the OLGA/OLGIM stages III/IV and gastric cancer. The
      Newcastle-Ottawa Scale (NOS) score reflected heterogeneity in the case-control
      studies on OLGA. Subgroup analysis of high-quality (NOS score >= 5) studies
      showed an association between OLGA stage III/IV and increased risk of gastric
      cancer; the association was also high in the remaining study with low NOS score.
      The association between higher stages of gastritis defined by OLGA and risk of
      gastric cancer was significant. CONCLUSIONS: This correlation implies that close
      and frequent monitoring of such high-risk patients is necessary to facilitate
      timely diagnosis of gastric cancer.

PMID- 29460005
TI  - Impact of pannus formation on hemodynamic dysfunction of prosthetic aortic valve:
      pannus extent and its relationship to prosthetic valve motion and degree of
      stenosis.
AB  - BACKGROUND: Although pannus is an important cause of prosthetic valve
      dysfunction, the minimum pannus size that can induce hemodynamic dysfunction has
      not yet been determined. This study investigated the correlation between the
      limitation of motion (LOM) of the prosthetic valve and pannus extent and
      determined the pannus extent that could induce severe aortic stenosis. METHODS:
      This study included 49 patients who underwent mechanical aortic valve replacement
      (AVR) and showed pannus on cardiac computed tomography (CT). Pannus width, ratio
      of pannus width to valve diameter, pannus area, effective orifice area,
      encroachment ratio by pannus, pannus involvement angle and percent LOM of
      mechanical valves were evaluated on CT. Transvalvular peak velocity (TPV) and
      transvalvular pressure gradient (TPG) were measured by transesophageal
      echocardiography to determine the degree of aortic stenosis. The relationship
      between percent LOM of the prosthetic valve and pannus extent and the cut-off of
      pannus extent required to induce severe aortic stenosis were evaluated. RESULTS:
      The mean interval between AVR and pannus formation was 11 years and was longer in
      patients with than without severe aortic stenosis (14.0 vs. 7.3 years). On CT,
      the percent LOM of the prosthetic valve was significantly associated with the
      extent of pannus only in patients with pannus involvement angle > 180 degrees  (r
      = 0.55-0.68, P < 0.01). Pannus width, effective orifice area, and encroachment
      ratio were significantly associated with increased TPV and TPG (r = 0.51-0.62, P
      < 0.01). Pannus width > 3.5 mm, pannus width/valve inner diameter > 0.15, and
      encroachment ratio > 0.14 were significantly associated with severe aortic
      stenosis (TPV > 4 m/s; mean TPG >= 35 mmHg), with c-indices of 0.74-079 (P <
      0.005). CONCLUSION: CT-derived pannus extent parameters are good indicators of
      significant hemodynamic changes with increased TPV and mean TPG.

PMID- 29460006
TI  - Mechanical disruption of the blood-brain barrier following experimental
      concussion.
AB  - Although concussion is now recognized as a major health issue, its non-lethal
      nature has limited characterization of the underlying pathophysiology. In
      particular, potential neuropathological changes have typically been inferred from
      non-invasive techniques or post-mortem examinations of severe traumatic brain
      injury (TBI). Here, we used a swine model of head rotational acceleration based
      on human concussion to examine blood-brain barrier (BBB) integrity after injury
      in association with diffuse axonal injury and glial responses. We then determined
      the potential clinical relevance of the swine concussion findings through
      comparisons with pathological changes in human severe TBI, where post-mortem
      examinations are possible. At 6-72 h post-injury in swine, we observed multifocal
      disruption of the BBB, demonstrated by extravasation of serum proteins,
      fibrinogen and immunoglobulin-G, in the absence of hemorrhage or other focal
      pathology. BBB disruption was observed in a stereotyped distribution consistent
      with biomechanical insult. Specifically, extravasated serum proteins were
      frequently observed at interfaces between regions of tissue with differing
      material properties, including the gray-white boundary, periventricular and
      subpial regions. In addition, there was substantial overlap of BBB disruption
      with regions of axonal pathology in the white matter. Acute perivascular cellular
      uptake of blood-borne proteins was observed to be prominent in astrocytes (GFAP
      positive) and neurons (MAP-2-positive), but not microglia (IBA1-positive).
      Parallel examination of human severe TBI revealed similar patterns of serum
      extravasation and glial uptake of serum proteins, but to a much greater extent
      than in the swine model, attributed to the higher injury severity. These data
      suggest that BBB disruption represents a new and important pathological feature
      of concussion.

PMID- 29460008
TI  - Correction to: 12. Deutscher Wirbelsaulenkongress Jahrestagung der Deutschen
      Wirbelsaulengesellschaft, 30. November - 2. Dezember 2017, Stuttgart.
AB  - Unfortunately, the abstract from V.

PMID- 29460009
TI  - The Global Spine Care Initiative: applying evidence-based guidelines on the non
      invasive management of back and neck pain to low- and middle-income communities.
AB  - PURPOSE: The purpose of this review was to develop recommendations for the
      management of spinal disorders in low-income communities, with a focus on non
      invasive pharmacological and non-pharmacological therapies for non-specific low
      back and neck pain. METHODS: We synthesized two evidence-based clinical practice
      guidelines for the management of low back and neck pain. Our recommendations
      considered benefits, harms, quality of evidence, and costs, with attention to
      feasibility in medically underserved areas and low- and middle-income countries.
      RESULTS: Clinicians should provide education and reassurance, advise patients to
      remain active, and provide information about self-care options. For acute low
      back and neck pain without serious pathology, primary conservative treatment
      options are exercise, manual therapy, superficial heat, and nonsteroidal anti
      inflammatory drugs (NSAIDs). For patients with chronic low back and neck pain
      without serious pathology, primary treatment options are exercise, yoga,
      cognitive behavioral therapies, acupuncture, biofeedback, progressive relaxation,
      massage, manual therapy, interdisciplinary rehabilitation, NSAIDs, acetaminophen,
      and antidepressants. For patients with spinal pain with radiculopathy, clinicians
      may consider exercise, spinal manipulation, or NSAIDs; use of other interventions
      requires extrapolation from evidence regarding effectiveness for non-radicular
      spinal pain. Clinicians should not offer treatments that are not effective,
      including benzodiazepines, botulinum toxin injection, systemic corticosteroids,
      cervical collar, electrical muscle stimulation, short-wave diathermy,
      transcutaneous electrical nerve stimulation, and traction. CONCLUSION: Guidelines
      developed for high-income settings were adapted to inform a care pathway and
      model of care for medically underserved areas and low- and middle-income
      countries by considering factors such as costs and feasibility, in addition to
      benefits, harms, and the quality of underlying evidence. The selection of
      recommended conservative treatments must be finalized through discussion with the
      involved community and based on a biopsychosocial approach. Decision determinants
      for selecting recommended treatments include costs, availability of
      interventions, and cultural and patient preferences. These slides can be
      retrieved under Electronic Supplementary Material.

PMID- 29460007
TI  - Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation
      status are associated with specific genetic risk loci.
AB  - Recent genome-wide association studies of glioma have led to the discovery of
      single nucleotide polymorphisms (SNPs) at 25 loci influencing risk. Gliomas are
      heterogeneous, hence to investigate the relationship between risk SNPs and glioma
      subtype we analysed 1659 tumours profiled for IDH mutation, TERT promoter
      mutation and 1p/19q co-deletion. These data allowed definition of five molecular
      subgroups of glioma: triple-positive (IDH mutated, 1p/19q co-deletion, TERT
      promoter mutated); TERT-IDH (IDH mutated, TERT promoter mutated, 1p/19q-wild
      type); IDH-only (IDH mutated, 1p/19q wild-type, TERT promoter wild-type); triple
      negative (IDH wild-type, 1p/19q wild-type, TERT promoter wild-type) and TERT-only
      (TERT promoter mutated, IDH wild-type, 1p/19q wild-type). Most glioma risk loci
      showed subtype specificity: (1) the 8q24.21 SNP for triple-positive glioma; (2)
      5p15.33, 9p21.3, 17p13.1 and 20q13.33 SNPs for TERT-only glioma; (3) 1q44,
      2q33.3, 3p14.1, 11q21, 11q23.3, 14q12, and 15q24.2 SNPs for IDH mutated glioma.
      To link risk SNPs to target candidate genes we analysed Hi-C and gene expression
      data, highlighting the potential role of IDH1 at 2q33.3, MYC at 8q24.21 and STMN3
      at 20q13.33. Our observations provide further insight into the nature of
      susceptibility to glioma.

PMID- 29460010
TI  - Type V osteogenesis imperfecta undergoing surgical correction for scoliosis.
AB  - PURPOSE: The objective of this article is to report a case of type V osteogenesis
      imperfecta (OI) undergoing posterior instrumented fusion for scoliosis. Type V OI
      is a moderately severe dysplasia causing primary defects in endochondral bone
      ossification or mineralisation. It is characterised by hyperplastic callus (HPC)
      formation, interosseous membrane calcifications, poor bone quality and spinal
      deformities including scoliosis. Data on the surgical management of spinal
      deformities in this patient group are lacking. CASE REPORT: A 16-year-old patient
      with a confirmed diagnosis of type V OI presented with a progressive scoliosis.
      The patient underwent a T3-L4 posterior instrumented correction and fusion
      utilising pedicle screws, pedicle hooks and sub-laminar wiring. At 4 months after
      surgery, the pedicle hooks pulled out and required partial metalwork removal
      after CT scanning confirmed bony union and no evidence of HPC formation. The
      patient was successfully discharged with satisfactory correction, confirmed bony
      union, no neurologic complication and absence of any hyperplastic callus
      formation. CONCLUSION: Type V OI patients requiring surgical intervention for
      scoliosis correction can safely undergo posterior instrumented fusion using
      sublaminar wiring and pedicle hook/screw constructs without apparent risk of HPC
      formation around neural elements. Surgery in this patient group remains
      challenging due to the associated poor bone quality. LEVEL OF EVIDENCE: V.

PMID- 29460012
TI  - ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro
      inflammatory molecular changes in the rabbit anular-puncture model and
      degenerated disc-induced pain generation in the rat xenograft radiculopathy
      model.
AB  - PURPOSE: To elucidate the effects of growth differentiation factor-6 (GDF6) on:
      (i) gene expression of inflammatory/pain-related molecules and structural
      integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii)
      sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia
      (DRGs) in the rat xenograft radiculopathy model. METHODS: Forty-six adolescent
      rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks
      later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 ug) was injected
      into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for
      gene expression analysis and 12 weeks for structural analyses. For pain
      assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP
      tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to
      examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically.
      RESULTS: In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor
      necrosis factor-alpha, vascular endothelial growth factor, prostaglandin
      endoperoxide synthase 2, and nerve growth factor were significantly lower than
      those in the PBS group. GDF6 injections resulted in partial restoration of disc
      height and improvement of MRI disc degeneration grades with statistical
      significance in rabbit structural analyses. Allodynia induced by xenograft
      transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced
      by GDF6 injection. Staining intensities for ionized calcium-binding adaptor
      molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were
      significantly lower than those of the PBS group. CONCLUSION: GDF6 injection may
      change the pathological status of degenerative discs and attenuate degenerated
      IVD-induced pain.

PMID- 29460011
TI  - ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory,
      psychological, and sleep-related factors following an acute low back pain episode
      the good, the bad, and the ugly.
AB  - STUDY DESIGN: Prospective longitudinal study. OBJECTIVE: To determine whether
      systemic cytokines and C-reactive protein (CRP) during an acute episode of low
      back pain (LBP) differ between individuals who did and did not recover by 6
      months and to identify sub-groups based on patterns of inflammatory,
      psychological, and sleep features associated with recovery/non-recovery. Systemic
      inflammation is observed in chronic LBP and may contribute to the transition from
      acute to persistent LBP. Longitudinal studies are required to determine whether
      changes present early or develop over time. Psychological and/or sleep-related
      factors may be related. METHODS: Individuals within 2 weeks of onset of acute LBP
      (N = 109) and pain-free controls (N = 55) provided blood for assessment of CRP,
      tumor necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-1beta, and
      completed questionnaires related to pain, disability, sleep, and psychological
      status. LBP participants repeated measurements at 6 months. Biomarkers were
      compared between LBP and control participants at baseline, and in longitudinal
      (baseline/6 months) analysis, between unrecovered (>=pain and disability),
      partially recovered (reduced pain and/or disability) and recovered (no pain and
      disability) participants at 6 months. We assessed baseline patterns of
      inflammatory, psychological, sleep, and pain data using hierarchical clustering
      and related the clusters to recovery (% change in pain) at 6 months. RESULTS: CRP
      was higher in acute LBP than controls at baseline. In LBP, baseline CRP was
      higher in the recovered than non-recovered groups. Conversely, TNF was higher at
      both time-points in the non-recovered than recovered groups. Two sub-groups were
      identified that associated with more ("inflammatory/poor sleep") or less ("high
      TNF/depression") recovery. CONCLUSIONS: This is the first evidence of a
      relationship between an "acute-phase" systemic inflammatory response and recovery
      at 6 months. High inflammation (CRP/IL-6) was associated with good recovery, but
      specific elevation of TNF, along with depressive symptoms, was associated with
      bad recovery. Depression and TNF may have a two-way relationship. These slides
      can be retrieved under Electronic Supplementary Material.

PMID- 29460013
TI  - EUROSPINE 2017 FULL PAPER AWARD: Time to remove our rose-tinted spectacles: a
      candid appraisal of the relative success of surgery in over 4500 patients with
      degenerative disorders of the lumbar spine, hip or knee.
AB  - PURPOSE: Studies comparing the outcome of spine surgery with that of large-joint
      replacement report equivocal findings. The patient-reported outcome measures
      (PROMs) used in such studies are typically generic and may not be sufficiently
      sensitive to the successes/failures of treatment. This study compared different
      indices of "success" in patients undergoing surgery for degenerative disorders of
      the lumbar spine, hip, or knee, using a validated, multidimensional, and joint
      specific PROM. METHODS: Preoperatively and 12 months postoperatively, 4594
      patients (3937 lumbar spine, 368 hip, 269 knee) undergoing first-time surgery
      completed a PROM that included the Core Outcome Measures Index (COMI) for the
      affected joint. The latter comprises a set of single items on pain, function,
      symptom-specific well-being, quality of life, and disability-all in relation to
      the specified joint problem. Other single-item ratings of treatment success were
      made 12 months postoperatively. RESULTS: In multiple regression analyses,
      controlling for confounders, the mean improvement in COMI at 12 months was
      greatest for the hip patients and lowest for those with degenerative spinal
      deformity (= the statistical reference group) (p < 0.05). Compared with spinal
      deformity, the odds of achieving "success" were: higher for hip (OR 4.6; 95% CI
      2.5-8.5) and knee (OR 4.0; 95% CI 2.1-7.7) (no difference between spine
      subgroups) for "satisfaction with care"; higher for hip (OR 16.9; 95% CI 7.3
      39.6), knee (OR 6.3; 95% CI 3.4-11.6), degenerative spondylolisthesis (OR 1.6;
      95% CI 1.2-2.2), and herniated disc (OR 1.7; 95% CI 1.2-2.4) for "global
      treatment outcome"; and higher for hip (OR 13.8; 95% CI 8.8-21.6), knee (OR 5.3;
      95% CI 3.6-7.8), degenerative spondylolisthesis (OR 1.6; 95% CI 1.3-2.1), and
      herniated disc (1.5; 95% CI 1.1-2.0) for "patient-acceptable symptom state".
      Patient-rated complications were the greatest in degenerative spinal deformity
      (29%) and the lowest in hip (18%). CONCLUSIONS: The current study is the largest
      of its kind and the first to use a common, but joint-specific instrument to
      report patient-reported outcomes after surgery for degenerative disorders of the
      spine, hip, or knee. The findings provide a sobering account of the significantly
      poorer outcomes after spine surgery compared with large-joint replacement.
      Further work is required to hone the indications and patient selection criteria
      for spine surgery. The data should be used to lobby research funding-bodies,
      governmental agencies, industry, and charitable foundations to invest more in
      spine research/registries, in the hope of ultimately improving spine outcomes.
      These slides can be retrieved under Electronic Supplementary Material.

PMID- 29460014
TI  - [A rare cause of swelling in the parotid region].

PMID- 29460015
TI  - [Immuno-, radio-, and chemotherapeutic studies in head and neck cancer :
      Highlights of the ASCO Annual Meeting 2017].
AB  - In recent years, immunotherapy has been shown to be a promising approach for the
      treatment of various tumor entities. Due to further pharmacological developments
      and new studies, the checkpoint inhibitors have now arrived in the clinic. To
      date, patients with cancers in the head and neck region have benefited from these
      agents as part of a palliative therapy. Current clinical trials are testing other
      indications for the checkpoint inhibitors as monotherapy or in combination with
      other therapeutic approaches. The following article summarizes the highlights of
      the American Society of Clinical Oncology (ASCO) Annual Meeting.

PMID- 29460016
TI  - [Secondary acquired lacrimal duct obstruction and cervical lymphadenopathy].

PMID- 29460017
TI  - Twenty five-gauge endoscopic vitrectomy for proliferative vitreoretinopathy with
      severe corneal opacity.
AB  - PURPOSE: To report 4 cases undergoing 25-gauge endoscopic vitrectomy for the
      treatment of proliferative vitreoretinopathy with severe corneal opacity in which
      a transpupillary view of the fundus was not possible. STUDY DESIGN: A
      retrospective interventional case series. METHODS: The main outcomes measured
      were postoperative anatomic status of the retina and subjective improvement of
      vision. RESULTS: Postoperative reattachment of the retina and subjective
      improvement of vision were achieved in all 4 eyes. CONCLUSION: Twenty five-gauge
      endoscopic vitrectomy provides a clear view making it possible conduct pars plana
      vitrectomy in order to reattach the retina in cases of proliferative
      vitreoretinopathy with severe corneal opacity.

PMID- 29460018
TI  - Observation of neovascularization of the disc associated with proliferative
      diabetic retinopathy using OCT angiography.
AB  - PURPOSE: To describe the relationship between the vitreous and the
      neovascularization of the disc (NVD) using swept source optical coherence
      tomography (SS-OCT) and OCT angiography (OCTA). STUDY DESIGN: Retrospective.
      METHODS: We examined 17 eyes of 11 consecutive patients diagnosed as NVD
      associated with proliferative diabetic retinopathy (PDR). The location of the NVD
      feeder or collector vessels were examined by using RTVue XR Avanti. To determine
      the condition of the posterior vitreous detachment (PVD) and the proliferative
      tissue of the NVD, we performed 12 mm horizontal and vertical scans through the
      disc using SS-OCT. RESULTS: OCT images of all 17 cases indicated there was no PVD
      on the optic disc. OCTA showed that the locations of the newly formed vessels
      from the optic disc were overwhelmingly outside the physiological cupping (95%).
      No cases exhibited formation of neovascularization inside the physiological
      cupping. OCT images revealed all 17 eyes had proliferative tissues located under
      the posterior wall of the vitreous, with 12 out of 17 eyes exhibiting additional
      invasion of the proliferative tissue into the vitreous through the posterior
      wall. Epiretinal membrane or a thickened posterior wall of the vitreous was
      present in 10 out of the 17 eyes. CONCLUSIONS: NVD associated with PDR arises
      from outside the physiological cupping and grows along the posterior wall of the
      vitreous. The absence of PVD on the optic disc is essential to the growth of NVD.

PMID- 29460019
TI  - Association between characteristics of foveal cystoid spaces and short-term
      responsiveness to ranibizumab for diabetic macular edema.
AB  - PURPOSE: To investigate the association between the characteristics of foveal
      cystoid spaces and short-term responsiveness to ranibizumab treatment for
      diabetic macular edema (DME) at 3 months from the initial injection. METHODS: We
      retrospectively reviewed 66 eyes of 61 patients with center-involved DME who
      received three consecutive ranibizumab injections and following as-needed
      administrations. We evaluated the relationship between visual improvement at 3
      months and the preoperative optical coherence tomography (OCT) parameters
      including hyperreflective foci, heterogeneous OCT reflectivity, mean levels of
      OCT reflectivity and height of foveal cystoid spaces. RESULTS: Twenty-three eyes
      without preoperative hyperreflective foci in the foveal cystoid spaces had
      significantly greater improvement in the logarithm of the minimum angle of
      resolution visual acuity (logMAR VA) at 3 months than 43 eyes with foci (P =
      0.006). That was similar to the greater reduction in CSF thickness in eyes
      without lesions after treatment at the same time point (P < 0.001). VA
      improvement at 3 months was not associated with the height (R = 0.215, P = 0.083)
      or the reflectivity levels (R = -0.079, P = 0.538) of foveal cystoid spaces.
      There were no differences in VA changes between eyes with and without
      heterogeneous reflectivity in foveal cystoid spaces (P = 0.297). Multivariate
      analyses showed that logMAR VA and the absence of hyperreflective foci in foveal
      cystoid spaces were associated with VA improvement at 3 months. CONCLUSION:
      Hyperreflective foci in foveal cystoid spaces at baseline predict poorer short
      term responsiveness to ranibizumab injections for DME.

PMID- 29460020
TI  - Periodontitis May Restrain the Mandibular Bone Healing via Disturbing Osteogenic
      and Osteoclastic Balance.
AB  - Periodontitis has been advocated as a systematic chronic low-grade infection
      burden. However, the relationship between periodontitis and bone defect healing
      has not been elucidated. One hundred and eight male Wister rats were randomly
      assigned into three groups: control (healthy) group, periodontitis group, and
      periodontitis plus human tumor necrosis factor receptorII:IgG Fc fusion protein
      (rhTNFR:Fc) group. The experimental periodontitis model was established by
      ligaturing with orthodontic wire and silk suture plus local administration of 20
      MUl of lipopolysaccharide (LPS). Mandibular bone defects in size of 4 * 2 * 1 mm
      were created for all the rats and rhTNFR:Fc subcutaneously injected at neck at a
      dose of 2.5 mg/kg every 3 days for the periodontitis plus rhTNFR:Fc group. The
      gene and protein expressions of bone-related markers in the healing tissue were
      monitored and new bone formation was histologically evaluated. Tartrate-resistant
      acid phosphatase (TRAP) staining was performed to determine the number of
      osteoclasts. The results showed that the mRNA and protein expressions of
      osteogenesis-related markers were significantly lower while nuclear factor of
      activated T cells, cytoplasmic 1 (NFATc1) gene expression was significantly
      higher in the periodontitis group. The periodontitis group showed decreased new
      bone formation and increased number of osteoclasts when compared to the control
      group. However, there was no significant difference between the periodontitis
      plus rhTNFR:Fc group and the control group. These results demonstrated that
      periodontitis may restrain the mandibular bone healing via disturbing osteogenic
      and osteoclastic balance in which tumor necrosis factor-alpha (TNF-alpha) could
      act as a leverage.

PMID- 29460021
TI  - The Role of TNF Family Molecules Light in Cellular Interaction Between Airway
      Smooth Muscle Cells and T Cells During Chronic Allergic Inflammation.
AB  - Interaction between T cells and airway smooth muscle (ASM) cells has been
      identified as an important factor in the development of asthma. LIGHT (known as
      TNFSF14) -mediated signaling likely contributes to various inflammatory disorders
      and airway remodeling. The objective of this study was to investigate the roles
      of LIGHT-mediated pathways in the interaction between ASM cells and T cells
      during chronic allergic inflammation. Mice were sensitized and challenged by
      ovalbumin (OVA) to induce chronic airway allergic inflammation. The control group
      received PBS only. The histological features and LIGHT expressions in lungs were
      assessed in vivo. Furthermore, T cells and ASM cells derived from the model mice
      were co-cultured both in the presence and absence of anti-LIGHT Ab for 72 h. The
      effects of LIGHT blockade on expressions of downstream signaling molecules,
      proliferation, and apoptosis of ASM cells, differentiation of T cells, and
      inflammatory cytokines release were evaluated. We demonstrated that LIGHT
      blockade strikingly inhibited the mRNA and protein expressions of HVEM, c-JUN,
      and NFkappaB. Additionally, LIGHT blockade resulted in decreased proliferation
      and increased apoptosis of ASM cells. Moreover, depletion of LIGHT dramatically
      reduced the differentiation of CD4+ T cells into Th1, Th2, and Th17 cells, as
      well as inhibited inflammatory cytokines release including IL-13, TGF-beta, and
      IFN-gamma, which are associated with CD4+ T cell differentiation and ASM cell
      proliferation. LIGHT plays an important role in the interaction between T cells
      and ASM cells in chronic allergic asthma. Blockade of LIGHT markedly suppressed
      ASM hyperplasia and inflammatory responses, which might be modulated through HVEM
      NFkappaB or c-JUN pathways. Therefore, targeting LIGHT is a promising therapeutic
      strategy for airway inflammation and remodeling in chronic allergic asthma.

PMID- 29460022
TI  - Correction to: Association between discordance of LDL-C and non-HDL-C and
      clinical outcomes in patients with stent implantation: from the FU-Registry.
AB  - Unfortunately, the Fig. 1 was published incorrectly in the original publication
      of the article. The correct figure is as below.

PMID- 29460023
TI  - Industry Perspective on Standardizing Food-Effect Studies for New Drug
      Development.
AB  - Investigating the effect of food on bioavailability during the development of an
      oral drug product is of prime importance because it has major implications on the
      study design of the clinical trials and dosing and administration
      recommendations. For modified-release formulations that exhibit dose dumping when
      administered with food, this may result in clinical concerns around safety and
      efficacy. In this article, we provide an overview of the various considerations
      in our opinion that impact the design and conduct of food-effect studies. We
      summarize the various recommendations from the different regulatory agencies and
      provide specific suggestions on study conduct in terms of statistical design,
      timing of studies, subject selection, and type and caloric content of the meal.
      We also discuss the role of modeling and simulation. Finally, we present an
      interpretation of the results of food-effect studies in addition to dosing and
      labeling recommendations in relation to regulatory guidance documents.

PMID- 29460024
TI  - Defining the optimal method for measuring baseline metabolic tumour volume in
      diffuse large B cell lymphoma.
AB  - PURPOSE: Metabolic tumour volume (MTV) is a promising prognostic indicator in
      diffuse large B cell lymphoma (DLBCL). Optimal thresholds to divide patients into
      'low' versus 'high' MTV groups depend on clinical characteristics and the
      measurement method. The aim of this study was to compare in consecutive
      unselected patients with DLBCL, different software algorithms and published
      methods of MTV measurement using FDG PET. METHOD: Pretreatment MTV was measured
      on 147 patients treated at Guy's and St Thomas' Hospital. We compared 3 methods:
      SUV >=2.5, SUV >=41% of maximum SUV and SUV >= mean liver uptake (PERCIST) and
      compared 2 software programs for measuring SUV >=2.5; in-house 'PETTRA' software
      and Hermes commercial software. RESULTS: There was strong correlation between MTV
      using the 4 methods, although derived thresholds were very different for the 41%
      method. Optimal cut-offs for predicting PFS ranged from 166-400cm3. All methods
      predicted survival with similar accuracy. 5y-PFS was 83-87% vs. 42-44% and 5y-OS
      was 85-89% vs. 55-58% for the low- and high-MTV groups, respectively.
      Interobserver variation in 50 patients showed excellent agreement, though
      variation was lowest using the SUV >= 2.5 method. The 41% method was the most
      complex and took the longest time. CONCLUSION: All methods predicted PFS and OS
      with similar accuracy, but the derived cut-off separating good from poor
      prognosis varied markedly depending on the method. The choice of the optimal
      method should rely primarily on prognostic value, but for clinical use needs to
      take account of ease of use and reproducibility. In this study, all methods
      predicted prognosis, but SUV >= 2.5 had the best inter-observer agreement and was
      easiest to apply.

PMID- 29460025
TI  - Combined model-based and patient-specific dosimetry for 18F-DCFPyL, a PSMA
      targeted PET agent.
AB  - PURPOSE: Prostate-specific membrane antigen (PSMA), a type-II integral membrane
      protein highly expressed in prostate cancer, has been extensively used as a
      target for imaging and therapy. Among the available PET radiotracers, the low
      molecular weight agents that bind to PSMA are proving particularly effective. We
      present the dosimetry results for 18F-DCFPyL in nine patients with metastatic
      prostate cancer. METHODS: Nine patients were imaged using sequential PET/CT scans
      at approximately 1, 12, 35 and 70 min, and a final PET/CT scan at approximately
      120 min after intravenous administration of 321 +/- 8 MBq (8.7 +/- 0.2 mCi) of18F
      DCFPyL. Time-integrated-activity coefficients were calculated and used as input
      in OLINDA/EXM software to obtain dose estimates for the majority of the major
      organs. The absorbed doses (AD) to the eye lens and lacrimal glands were
      calculated using Monte-Carlo models based on idealized anatomy combined with
      patient-specific volumes and activity from the PET/CT scans. Monte-Carlo based
      models were also developed for calculation of the dose to two major salivary
      glands (parotid and submandibular) using CT-based patient-specific gland volumes.
      RESULTS: The highest calculated mean AD per unit administered activity of 18F was
      found in the lacrimal glands, followed by the submandibular glands, kidneys,
      urinary bladder wall, and parotid glands. The S-values for the lacrimal glands to
      the eye lens (0.42 mGy/MBq h), the tear film to the eye lens (1.78 mGy/MBq h) and
      the lacrimal gland self-dose (574.10 mGy/MBq h) were calculated. Average S-values
      for the salivary glands were 3.58 mGy/MBq h for the parotid self-dose and 6.78
      mGy/MBq h for the submandibular self-dose. The resultant mean effective dose of
      18F-DCFPyL was 0.017 +/- 0.002 mSv/MBq. CONCLUSIONS: 18F-DCFPyL dosimetry in nine
      patients was obtained using novel models for the lacrimal and salivary glands,
      two organs with potentially dose-limiting uptake for therapy and diagnosis which
      lacked pre-existing models.

PMID- 29460026
TI  - 11C-acetate PET/CT: a potential alternative of transcranial biopsy for grading
      cerebral gliomas.

PMID- 29460027
TI  - Could short thyroid hormone withdrawal be an effective strategy for radioiodine
      remnant ablation in differentiated thyroid cancer patients?
AB  - PURPOSE: Current guidelines recommend thyroid hormone withdrawal (THW) of 3-4
      weeks before radioiodine remnant ablation (RRA) of differentiated thyroid
      carcinoma (DTC). We aimed to evaluate (1) the reliability of a shorter THW (i.e.,
      14 days) to achieve adequate TSH levels (i.e., 30 mU/l), (2) the association
      between length of THW and response to therapy, and (3) the potential association
      between pre-ablation TSH levels and patients' outcome. METHODS: After
      thyroidectomy, all patients started LT4 therapy, which was subsequently
      discontinued in order to perform RRA. Patients were broken down into two groups
      according to the length of THW: group A, 2 weeks of THW, and group B, 3-4 weeks
      of THW. We used clinical, biochemical, and imaging data to evaluate patients'
      outcome. By means of univariate and multivariate analysis, including main DTC
      prognostic factors, we assessed the impact of THW length and TSH levels on
      patients' outcome. RESULTS: We evaluated 222 patients, 85 of whom were treated
      with RRA after a THW period of 2 weeks (group A). All other 137 patients
      underwent RRA after 3-4 weeks THW (group B). At the time of RRA all patients
      presented TSH levels >=30 mU/l. After a median follow-up time of 3.4 years, we
      found 183 patients (82%) with excellent response to treatment and 39 patients
      (18%) showing incomplete response. Kaplan-Meier response to therapy curves showed
      that ablation-Tg, tumor size, and lymph node status were significantly associated
      with prognosis; no associations were found between THW length, TSH levels, and
      prognosis. Multivariate Cox model showed that only ablation-Tg was significantly
      associated with treatment response. CONCLUSIONS: Prior to RRA, a short 2-week THW
      is an effective method to stimulate TSH levels. No difference in terms of
      incomplete response to treatment was observed between DTC patients prepared for
      RRA with a short THW and those with the long THW.

PMID- 29460028
TI  - Hydrodynamics affect predator controls through physical and sensory stressors.
AB  - Predators influence communities through either consuming prey (consumptive
      effects, CEs) or altering prey traits (non-consumptive effects, NCEs), which has
      cascading effects on lower trophic levels. CEs are well known to decrease in
      physically stressful environments, but NCEs may be reduced at physically benign
      levels that affect the ability of prey to detect and respond to predators (i.e.,
      sensory stress). We investigated the influence of physical and sensory stressors
      created by spatial and temporal differences in tidal flow on predator controls in
      a tritrophic system. We estimated mud crab reactive ranges to blue crab NCEs by
      evaluating mud crab CEs on juvenile oysters at different distances away from
      caged blue crabs across flow conditions. Mud crab reactive ranges were large at
      lower physical and sensory stress levels and blue crabs had a positive cascading
      effect on oyster survival. Blue crab NCEs were not important at higher flow
      conditions. Oyster survival was a complicated function of both types of
      stressors. Physical stress (i.e., current speed) had a positive effect on oyster
      survival by physically limiting mud crab CEs at high current speeds. Sensory
      stress (i.e., turbulence) interfered with the propagation of blue crab chemical
      cues used by mud crabs for predator detection, which removed blue crab NCEs. Mud
      crab CEs increased as a result and had a negative effect on oyster survival in
      turbulent conditions. Thus, environmental properties, such as fluid flow, can
      inflict physical and sensory stressors that have distinct effects on basal prey
      performance through impacts on different predator effects.

PMID- 29460029
TI  - Outcome of adult patients with X-linked hypophosphatemia caused by PHEX gene
      mutations.
AB  - X-linked hypophosphatemia (XLH) is the most common monogenic disorder causing
      hypophosphatemia. This case-note review documents the clinical features and the
      complications of treatment in 59 adults (19 male, 40 female) with XLH. XLH is
      associated with a large number of private mutations; 37 different mutations in
      the PHEX gene were identified in this cohort, 14 of which have not been
      previously reported. Orthopaedic involvement requiring surgical intervention
      (osteotomy) was frequent. Joint replacement and decompressive laminectomy were
      observed in those older than 40 years. Dental disease (63%), nephrocalcinosis
      (42%), and hearing impairment (14%) were also common. The rarity of the disease
      and the large number of variants make it difficult to discern specific genotype
      phenotype relationships. A new treatment, an anti-FGF23 antibody, that may affect
      the natural history of the disease is currently being investigated in clinical
      trials.

PMID- 29460030
TI  - Succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism: an
      update on pharmacological and enzyme-replacement therapeutic strategies.
AB  - We present an update to the status of research on succinic semialdehyde
      dehydrogenase (SSADH) deficiency (SSADHD), a rare disorder of GABA metabolism.
      This is an unusual disorder featuring the accumulation of both GABA and its
      neuromodulatory analog, gamma-hydroxybutyric acid (GHB), and recent studies have
      advanced the potential clinical application of NCS-382, a putative GHB receptor
      antagonist. Animal studies have provided proof-of-concept that enzyme replacement
      therapy could represent a long-term therapeutic option. The characterization of
      neuronal stem cells (NSCs) derived from aldehyde dehydrogenase 5a1-/- (aldh5a1-/
      ) mice, the murine model of SSADHD, has highlighted NSC utility as an in vitro
      system in which to study therapeutics and associated toxicological properties.
      Gene expression analyses have revealed that transcripts encoding GABAA receptors
      are down-regulated and may remain largely immature in aldh5a1-/- brain,
      characterized by excitatory as opposed to inhibitory outputs, the latter being
      the expected action in the mature central nervous system. This indicates that
      agents altering chloride channel activity may be therapeutically relevant in
      SSADHD. The most recent therapeutic prospects include mTOR (mechanistic target of
      rapamycin) inhibitors, drugs that have received attention with the elucidation of
      the effects of elevated GABA on autophagy. The outlook for novel therapeutic
      trials in SSADHD continues to improve.

PMID- 29460032
TI  - Metastasis of breast cancer prior to invasion.

PMID- 29460031
TI  - Acute toxicity of intraoperative radiotherapy and external beam-accelerated
      partial breast irradiation in elderly breast cancer patients.
AB  - BACKGROUND AND PURPOSE: We investigated the acute toxicity of accelerated partial
      breast irradiation using external beam (EB-APBI) or intraoperative radiotherapy
      (IORT) techniques in elderly breast cancer patients. MATERIALS AND METHODS: Women
      >= 60 years with unifocal breast tumors of <= 30 mm were eligible for this
      prospective multi-center cohort study. IORT was applied with electrons following
      lumpectomy (23.3 Gy). EB-APBI was delivered using 3D-CRT or IMRT in 10 daily
      fractions of 3.85 Gy within 6 weeks after surgery. Acute toxicity was scored
      using the CTCAE v3.0 at 3 months after treatment. Patient-reported symptoms were
      analyzed using visual analogue scales (VAS) for pain and fatigue (scale 0-10),
      and single items from the EORTC QLQ-C30 and Breast Cancer questionnaires.
      RESULTS: In total, 267 (IORT) and 206 (EB-APBI) patients were available for
      toxicity analysis. More patients experienced >= grade 2 CTCAE acute toxicity in
      the IORT group (10.4% IORT and 4.9% EB-APBI; p = 0.03); grade 3 toxicity was low
      (3.3% IORT and 1.5% EB-APBI; ns); and no grade 4 toxicity occurred. EB-APBI
      patients experienced less fatigue direct postoperatively (EORTC p < 0.00, VAS p <
      0.00). After 3 months only pain, according to the VAS scale, was significantly
      worse in the EB-APBI group (p < 0.00). CONCLUSION: Acute toxicity after IORT and
      EB-APBI treatment is acceptable.

PMID- 29460033
TI  - Factors associated with improved outcomes for metastatic inflammatory breast
      cancer patients.
AB  - PURPOSE: Controversy exists regarding the role of locoregional therapy for stage
      IV inflammatory breast cancer (IBC). This study aims to determine indicators of
      prognosis, including primary tumor resection, for stage IV IBC patients. METHODS:
      Using the National Cancer Data Base, female patients diagnosed 2010-2013 with
      unilateral a priori metastatic T4d invasive adenocarcinoma of the breast were
      identified. We conducted propensity score matched analysis to balance confounders
      of surgery versus no-surgery. Stratified log-rank test and double-robust
      estimation under the Cox model were used to assess the effect of surgery, and
      margins, on overall survival (OS) in the propensity score matched cohort.
      RESULTS: Of 1266 patients, 41% underwent surgery. In the unmatched cohort, median
      OS of the surgery and no-surgery groups was 36 and 20 months, respectively (p <
      0.001). In the matched cohort (n = 588), the median OS of surgery and no-surgery
      groups was 29 and 27 months, respectively (p = 0.052). Patients with negative
      margin surgery (p = 0.024), hormone receptor-positive (p = 0.019), HER2-positive
      disease (p < 0.0001), treated with chemotherapy (p < 0.0001) and hormonal therapy
      (p < 0.0001), had better survival. Those with brain metastases had increased risk
      of death (p < 0.0001). CONCLUSION: This study represents the largest cohort of
      metastatic IBC patients, and identified negative margin surgery, systemic
      therapy, hormone receptor and HER2-positive disease as factors associated with
      improved outcomes. While these findings should be interpreted cautiously, they
      may be used to guide further investigations into local control and quality of
      life in this patient population with limited treatment options.

PMID- 29460034
TI  - Remembering John M. Olson (1929-2017).
AB  - Here we provide reflections of and a tribute to John M. Olson, a pioneering
      researcher in photosynthesis. We trace his career, which began at Wesleyan
      University and the University of Pennsylvania, and continued at Utrech in The
      Netherlands, Brookhaven National Laboratory, and Odense University in Denmark. He
      was the world expert on pigment organization in the green photosynthetic
      bacteria, and discovered and characterized the first chlorophyll-containing
      protein, which has come to be known as the Fenna-Matthews-Olson (FMO) protein. He
      also thought and wrote extensively on the origin and early evolution of
      photosynthesis. We include personal comments from Brian Matthews, Raymond Cox,
      Paolo Gerola, Beverly Pierson and Jon Olson.

PMID- 29460035
TI  - Frequent genomic alterations and better prognosis among young patients with non
      small-cell lung cancer aged 40 years or younger.
AB  - BACKGROUND: The subgroup of young patients with non-small-cell lung cancer
      (NSCLC) is poorly understood. We retrospectively studied the clinical
      characteristics, gene mutations, and outcomes of patients with NSCLC (aged <= 40
      years). RESULTS: Of the 7494 patients with lung cancer diagnosed from February
      2001 to October 2016, 252 aged <= 40 years showed NSCLC. We divided their cases
      into non-squamous cell carcinoma and squamous cell carcinoma groups according to
      their histology results. Of the 252 young NSCLC patients, 173 (69%) patients had
      stage IIIB or IV, and 196 (78%) had never smoked. The four most common metastases
      were intrapulmonary lesions, pleura, bone, and brain. Among patients with
      adenocarcinoma, 29 (40%, n = 73) harbored epidermal growth factor receptor (EGFR)
      mutations, 25 (34%, n = 74) harbored anaplastic lymphoma kinase (ALK)
      translations, and 1 (14%, n = 7) harbored ROS proto-oncogene 1 receptor tyrosine
      kinase (ROS1) translations. The median progression-free survival (PFS) and
      overall survival (OS) were 3.3 and 27.6 months for patients receiving
      chemotherapy (n = 65), and 12.1 and 33.6 months for patients receiving EGFR
      tyrosine kinase inhibitors (TKIs) (n = 13), respectively. Patients receiving
      crizotinib had a median PFS time of 21.9 months (n = 8). CONCLUSIONS: Young
      patients are associated with an increased likelihood of gene mutations and can
      receive a better prognosis when patients harboring gene mutations are treated
      with EGFR-TKIs or ALK inhibitors.

PMID- 29460037
TI  - Incremental rate of prefrontal oxygenation determines performance speed during
      cognitive Stroop test: the effect of ageing.
AB  - Cognitive function declines with age. The underlying mechanisms responsible for
      the deterioration of cognitive performance, however, remain poorly understood. We
      hypothesized that an incremental rate of prefrontal oxygenation during a
      cognitive Stroop test decreases in progress of ageing, resulting in a slowdown of
      cognitive performance. To test this hypothesis, we identified, using multichannel
      near-infrared spectroscopy, the characteristics of the oxygenated-hemoglobin
      concentration (Oxy-Hb) responses of the prefrontal cortex to both incongruent
      Stroop and congruent word-reading test. Spatial distributions of the significant
      changes in the three components (initial slope, peak amplitude, and area under
      the curve) of the Oxy-Hb response were compared between young and elderly
      subjects. The Stroop interference time (as a difference in total periods for
      executing Stroop and word-reading test, respectively) approximately doubled in
      elderly as compared to young subjects. The Oxy-Hb in the rostrolateral, but not
      caudal, prefrontal cortex increased during the Stroop test in both age groups.
      The initial slope of the Oxy-Hb response, rather than the peak and area under the
      curve, had a strong correlation with cognitive performance speed. Taken together,
      it is likely that the incremental rate of prefrontal oxygenation may decrease in
      progress of ageing, resulting in a decline in cognitive performance.

PMID- 29460036
TI  - The mammalian circadian system: a hierarchical multi-oscillator structure for
      generating circadian rhythm.
AB  - The circadian nature of physiology and behavior is regulated by a circadian clock
      that generates intrinsic rhythms with a periodicity of approximately 24 h. The
      mammalian circadian system is composed of a hierarchical multi-oscillator
      structure, with the central clock located in the suprachiasmatic nucleus (SCN) of
      the hypothalamus regulating the peripheral clocks found throughout the body. In
      the past two decades, key clock genes have been discovered in mammals and shown
      to be interlocked in transcriptional and translational feedback loops. At the
      cellular level, each cell is governed by its own independent clock; and yet,
      these cellular circadian clocks in the SCN form regional oscillators that are
      further coupled to one another to generate a single rhythm for the tissue. The
      oscillatory coupling within and between the regional oscillators appears to be
      critical for the extraordinary stability and the wide range of adaptability of
      the circadian clock, the mechanism of which is now being elucidated with newly
      advanced molecular tools.

PMID- 29460039
TI  - CT colonography: the ideal colorectal cancer screening test.

PMID- 29460038
TI  - The Performance of Two Supertree Schemes Compared Using Synthetic and Real Data
      Quartet Input.
AB  - Despite impressive advancements in technological and theoretical tools,
      construction of phylogenetic (evolutionary) trees is still a challenging task.
      The availability of enormous quantities of molecular data has made large-scale
      phylogenetic reconstruction involving thousands of species, a more viable goal.
      For this goal, separate trees over different, overlapping subsets of species,
      representing histories of various markers of these species, are collected. These
      trees, typically with conflicting signals, are subsequently combined into a
      single tree over the full set, an operation denoted as supertree construction.
      The amalgamation of such trees into a single tree lies at the heart of many tasks
      in phylogenetics, yet remains a daunting endeavor, especially in light of
      conflicting signals. In this work, we study the performance of matrix
      representation with parsimony (MRP), the most widely used supertree method to
      date, when confronted with quartet trees. Quartet trees are the most basic
      informational unit when amalgamation of unrooted trees is attempted, and they
      remain relevant in more general settings even though standard supertree methods
      are not necessarily confined to quartets. This study involves both real and
      simulated data, and the effects of several parameters on the results are
      evaluated, revealing a number of anomalies associated with MRP. We show that
      these anomalies are surmountable when using a recently introduced supertree
      method, weighted quartet MaxCut (wQMC).

PMID- 29460040
TI  - Benign and malignant hepatocellular lesions in patients with vascular liver
      diseases.
AB  - A variety of vascular liver disorders can induce hepatocellular tumors. They may
      be related to portal venous deprivation, venous outflow obstruction, or arterial
      diseases. Their common feature is an imbalance between hepatic arterial and
      portal venous blood flow leading to an increased hepatic arterial inflow.
      Consequently, hepatocellular tumors may arise, most commonly focal nodular
      hyperplasia-like lesions but hepatocellular adenomas and hepatocellular carcinoma
      may be seen as well. This article will review the most common vascular liver
      diseases associated with hepatocellular nodules (Budd-Chiari syndrome, congenital
      portosystemic shunt, hereditary hemorrhagic telangiectasia, and portal
      cavernoma). For each condition, imaging findings will be described as well as the
      differential diagnosis and the diagnostic clues.

PMID- 29460041
TI  - Building a high-resolution T2-weighted MR-based probabilistic model of tumor
      occurrence in the prostate.
AB  - PURPOSE: We present a method for generating a T2 MR-based probabilistic model of
      tumor occurrence in the prostate to guide the selection of anatomical sites for
      targeted biopsies and serve as a diagnostic tool to aid radiological evaluation
      of prostate cancer. MATERIALS AND METHODS: In our study, the prostate and any
      radiological findings within were segmented retrospectively on 3D T2-weighted MR
      images of 266 subjects who underwent radical prostatectomy. Subsequent
      histopathological analysis determined both the ground truth and the Gleason grade
      of the tumors. A randomly chosen subset of 19 subjects was used to generate a
      multi-subject-derived prostate template. Subsequently, a cascading registration
      algorithm involving both affine and non-rigid B-spline transforms was used to
      register the prostate of every subject to the template. Corresponding
      transformation of radiological findings yielded a population-based probabilistic
      model of tumor occurrence. The quality of our probabilistic model building
      approach was statistically evaluated by measuring the proportion of correct
      placements of tumors in the prostate template, i.e., the number of tumors that
      maintained their anatomical location within the prostate after their
      transformation into the prostate template space. RESULTS: Probabilistic model
      built with tumors deemed clinically significant demonstrated a heterogeneous
      distribution of tumors, with higher likelihood of tumor occurrence at the mid
      gland anterior transition zone and the base-to-mid-gland posterior peripheral
      zones. Of 250 MR lesions analyzed, 248 maintained their original anatomical
      location with respect to the prostate zones after transformation to the prostate.
      CONCLUSION: We present a robust method for generating a probabilistic model of
      tumor occurrence in the prostate that could aid clinical decision making, such as
      selection of anatomical sites for MR-guided prostate biopsies.

PMID- 29460042
TI  - Spleen enlargement assessment using computed tomography: which coefficient
      correlates the strongest with the real volume of the spleen?
AB  - PURPOSE: The aim of the study was to find which linear measurements, field and
      volume coefficients correlate the best with real volume of the spleen and can be
      further used for identification of splenomegaly. METHODS: Abdominal computed
      tomography (CT) examinations of 264 patients were retrospectively analyzed in
      terms of maximal length, maximal thickness, hilum thickness, maximal height,
      vertical height and estimated height. Spleen volume was manually measured in
      Vitrea software. Two- and three-dimensional coefficients were calculated through
      proper mathematical formulas from linear measurements. Splenomegaly cut-off:
      314.5 cm3. Data were analyzed with use of Pearson correlation and chi2 test with
      statistical significance at p < 0.05. RESULTS: For single measurements, the
      correlation with real spleen volume was the strongest for maximal height (r =
      0.804; p < 0.05). Among two-dimensional indexes, multiplication product of
      maximal length and vertical height reached the highest level of correlation with
      spleen volume (r = 0.923; p < 0.05) and had the highest sensitivity and
      specificity (94.3% and 93.0%, respectively) for splenomegaly detection (threshold
      115 cm2). In case of three-dimensional ones, the coefficient calculated from
      maximal length, vertical height and hilum thickness established the strongest
      link with spleen volume (r = 0.956; p < 0.05). CONCLUSIONS: Coefficient
      calculated from maximal length, vertical height and hilum thickness correlates
      the strongest with spleen volume and can be utilized for monitoring of spleen
      volume instead of obsolete splenic index. The most suitable for quick
      splenomegaly screening is two-dimensional coefficient (maximal length * vertical
      height), with the cut-off 115 cm2.

PMID- 29460044
TI  - MRI features of primary hepatic lymphoma.
AB  - PURPOSE: Our retrospective study sought to describe the spectrum of magnetic
      resonance imaging (MRI) features of primary hepatic lymphoma (PHL) by analyzing
      its morphological aspects, signal intensity before and after contrast agent (CA)
      administration, and diffusion-weighted imaging (DwI) with the apparent diffusion
      coefficient (ADC) values. METHODS: A retrospective analysis was conducted on 25
      patients with pathologically proven PHL who underwent MRI between January 2011
      and December 2016. For the evaluation of the ADC, we used a control group of 87
      patients (22 with hepatocellular carcinoma, 15 with cholangiocellular carcinoma,
      23 with liver metastasis, 22 with focal nodular hyperplasia, and 5 with adenoma).
      Two radiologists evaluated the morphological features, the signal intensity
      before and after CA administration, and the DwI. The sensitivity and specificity
      of the ADC values in distinguishing the PHL lesions from other hepatic lesions
      were calculated by analyzing the receiver operating characteristic (ROC) curves.
      RESULTS: Twenty-one patients had non-Hodgkin's lymphoma (18 had diffuse large B
      cell lymphoma and three had mucosa-associated lymphoid tissue) and four had
      Hodgkin's lymphoma (nodular sclerosis). The PHL had a variable morphologic
      distribution (17 focal mass and eight multiple nodules) and mainly an insinuative
      growth (24/25). Usually, PHL was usually hypointense on the T1-weighted images
      (23/25) and hyperintense on the T2-weighted images (21/25); non-specific dynamic
      enhancement was found after CA administration, but in the hepatobiliary phase,
      PHL is mainly hypointense (92%). All PHLs showed a signal restriction in the DwI.
      The sensitivity and specificity in the differential diagnosis between PHL and the
      other malignant lesions were respectively 81.7% and 100%, with applying an ADC
      cut-off value of 0.918 * 10-3 mm2/s. CONCLUSION: Although PHL is a rare disease
      and biopsy is still required, an MRI could be indicative. In our series, PHL
      showed an insinuative growth, hypointense signal in the hepatobiliary phase,
      signal restriction in the DwI, and an ADC value lower than that of the other
      hepatic lesions analyzed.

PMID- 29460043
TI  - Low rate of spleen involvement in sporadic Burkitt lymphoma at staging on PET-CT.
AB  - BACKGROUND: Burkitt lymphoma is a highly aggressive B cell non-Hodgkin lymphoma.
      Cross-sectional imaging techniques that are used to detect liver and spleen
      involvement by lymphoma have high rates of false negative and false positive
      findings, and as such may reduce the accuracy of staging. PURPOSE: This
      retrospective study evaluated the use of FDG PET-CT in determining splenic
      involvement at staging, in a relatively large cohort of adult patients with the
      sporadic form of Burkitt lymphoma (SBL). PATIENTS AND METHODS: All adult patients
      who underwent FDG PET-CT for staging of SBL at one medical center during 2005
      2014 were enrolled for this retrospective study. RESULTS: Data were analyzed of
      20 patients, with median age 49 years; 17 were male. PET-CT revealed highly
      intense FDG uptake, mean SUV max 11.4 +/- 7.49 (range 4.3-38) in various tissues.
      None of the 20 patients had either focal or diffuse increased uptake of FDG in
      the spleen parenchyma. In 2 patients, there were highly FDG-avid soft tissue
      masses adjacent to the spleen, both in the context of direct peritoneal disease
      extension. CONCLUSION: The spleen is rarely involved in SBL at the time of
      staging, according to PET-CT, except in cases with direct extension from adjacent
      peritoneal mass. The low rate of spleen involvement according to PET-CT may serve
      as a specific characteristic of SBL. Larger-scale clinical studies incorporating
      PET-CT scans in SBL are needed to confirm our observation.

PMID- 29460045
TI  - Splenic contraction: a new member of the hypovolemic shock complex.
AB  - OBJECTIVE: The objective of the article is to assess changes in splenic volume in
      the setting of hypovolemic shock; splenic enhancement in hypovolemic shock is
      also assessed. MATERIALS/METHODS: 71 consecutive adult patients with the
      hypovolemic shock complex on computed tomography (CT) were identified. Spleen
      volume and enhancement were compared to a baseline CT scan (without shock) or to
      height- and sex-corrected normal values and a control population when a
      comparison CT was unavailable. RESULTS: Splenic volume was significantly lower in
      the setting of shock. Average splenic volume in adult patients with shock was 107
      +/- 63 cm3 compared to 220 +/- 164 cm3 in the control population (P < 0.001). All
      shock patients with a comparison CT (n = 35) had decreased splenic volume in the
      setting of shock. The area under the receiver operating characteristic (ROC)
      curve for spleen volume predicting shock was 0.83. Splenic enhancement was also
      significantly lower in the setting of shock. Mean splenic attenuation value in
      our shock population was 105 +/- 34 HU compared to 134 +/- 25 HU in the control
      population (P < 0.001). Decreased splenic enhancement was present in 25 of 71
      shock patients and in none of the control patients (P < 0.001). CONCLUSION:
      Decreased splenic volume is a ubiquitous and reliable sign of hypovolemic shock
      and should be considered a member of the hypovolemic shock complex. It is of
      particular utility when a prior study is available. Splenic hypoenhancement has
      high specificity and a high positive predictive value for hypovolemic shock in
      the correct patient population.

PMID- 29460046
TI  - Multiparametric US for scrotal diseases.
AB  - Multiparametric US is increasingly recognized as a valuable problem-solving
      technique in scrotal pathologies. Compared to conventional Doppler modes,
      contrast-enhanced ultrasonography (CEUS) has higher sensitivity in assessing the
      presence or absence of flows, and to improve differentiation between poorly
      vascularized tumors and non-neoplastic, avascular lesions. Characterization of
      benign and malignant complex cysts is improved. In trauma patients, CEUS can help
      evaluating the viability of testicular parenchyma. In patients with severe
      epididymo-orchitis, it allows unequivocal assessment of post-inflammatory
      ischemic changes and abscess formation. CEUS does not add significantly to
      conventional Doppler modes in spermatic cord torsion. Attempt of differentiating
      benign and malignant tumors remains a research tool. In the clinical practice,
      elastography has a limited role for tumor characterization. The majority of
      malignant tumors are stiff at elastography, but they may display soft areas, or
      appear globally soft. A quantitative evaluation of testicular stiffness is
      feasible using shear-wave elastography. Potential clinical applications for
      elastographic modes could include work-up of infertile patients.

PMID- 29460047
TI  - Point shear wave elastography of the pancreas in patients with cystic fibrosis: a
      comparison with healthy controls.
AB  - PURPOSE: Manifestations of cystic fibrosis in the pancreas are gaining in
      clinical importance as patients live longer. Conventional ultrasonography and
      point shear wave elastography (pSWE) imaging are non-invasive and readily
      available diagnostic methods that are easy to perform. The aim of this study was
      to perform conventional ultrasonography and obtain pSWE values in the pancreases
      of patients with cystic fibrosis and to compare the findings with those of
      healthy controls. METHODS: 27 patients with cystic fibrosis (13 women/14 men;
      mean age 27.7 +/- 13.7 years; range 9-58 years) and 60 healthy control subjects
      (30 women/30 men; mean age 30.3 +/- 10.0 years; range 22-55 years) underwent
      examinations of the pancreas with conventional ultrasound and pSWE imaging.
      RESULTS: Patients with cystic fibrosis have an echogenic pancreatic parenchyma.
      We found cystic lesions of the pancreas in six patients. pSWE imaging of the
      pancreatic parenchyma gave significantly lower shear wave velocities in patients
      with cystic fibrosis than in the control group (1.01 m/s vs 1.30 m/s; p < 0.001).
      CONCLUSIONS: Using pSWE imaging in vivo, we have shown that the pancreas is
      considerably softer in patients with cystic fibrosis than in a healthy control
      population.

PMID- 29460048
TI  - Abdominal aortic aneurysms: pre- and post-procedural imaging.
AB  - Abdominal aortic aneurysm (AAA) is a relatively common, potentially life
      threatening disorder. Rupture of AAA is potentially catastrophic with high
      mortality. Intervention for AAA is indicated when the aneurysm reaches 5.0-5.5 cm
      or more, when symptomatic, or when increasing in size > 10 mm/year. AAA can be
      accurately assessed by cross-sectional imaging including computed tomography
      angiography and magnetic resonance angiography. Current options for intervention
      in AAA patients include open surgery and endovascular aneurysm repair (EVAR),
      with EVAR becoming more prevalent over time. Cross-sectional imaging plays a
      crucial role in AAA surveillance, pre-procedural assessment, and post-EVAR
      management. This paper will discuss the current role of imaging in the assessment
      of AAA patients prior to intervention, in evaluation of procedural complications,
      and in long-term follow-up of EVAR patients.

PMID- 29460049
TI  - Double Blind Study Investigating the Effect of Different Voice Prostheses on Ease
      of Swallowing and Residue Post Laryngectomy.
AB  - Voice prostheses have been examined for their effect on voice production but
      there is little datum on their effect on swallow function. This study
      investigated the difference between six commonly available voice prostheses in
      terms of swallowing. Laryngectomy patients had up to six voice prostheses placed
      in a random order over two visits. Swallowing was evaluated for each prosthesis
      using FEES (Fibreoptic Endoscopic Evaluation of Swallowing). After each
      prosthesis trial, patients self-evaluated their experience of swallowing. Three
      independent experts indicated which prosthesis they considered best for
      swallowing for each patient and judged residue on the voice prosthesis and in the
      upper esophagus. Raters were blinded to participant details, voice prosthesis
      type and scores of other raters. On patient self-evaluation, scores were equally
      distributed across all prostheses for swallowing. Experts most frequently chose
      the Blom Singer Low pressure and Blom Singer Classic Indwelling voice prostheses
      as best for swallowing but consensus was poor for most patients. Experts found
      that the Blom Singer Classic Indwelling and the Provox Vega had least residue on
      the voice prosthesis on thin liquid (p <= 0.001) and soft (p = 0.001),
      respectively. Experts also found that the Blom Singer Low Pressure had least
      residue in the upper esophagus on soft consistency (p <= 0.001). While self
      evaluation by patients did not identify a consistently preferred prosthesis for
      swallow, many patients expressed personal preferences, suggesting benefits to
      involving patients in the choice of prosthesis. Some voice prostheses may be
      associated with lower levels of residue on the prosthesis and upper esophagus
      with certain consistencies.

PMID- 29460050
TI  - Imaging of cytotoxic antiviral immunity while considering the 3R principle of
      animal research.
AB  - : Adoptive cell transfer approaches for antigen-specific CD8+ T cells are used
      widely to study their effector potential during infections or cancer. However,
      contemporary methodological adaptations regarding transferred cell numbers,
      advanced imaging, and the 3R principle of animal research have been largely
      omitted. Here, we introduce an improved cell transfer method that reduces the
      number of donor animals substantially and fulfills the requirements for
      intravital imaging under physiological conditions. For this, we analyzed the well
      established Friend retrovirus (FV) mouse model. Donor mice that expressed a FV
      specific T cell receptor (TCRtg) and the fluorescent protein tdTomato were used
      as source of antigen-specific CD8+ T cells. Only a few drops of peripheral blood
      were sufficient to isolate ~ 150,000 naive reporter cells from which 1000 were
      adoptively transferred into recently FV-infected recipients. The cells became
      activated and functional and expanded strongly in the spleen and bone marrow
      within 10 days post infection. Transferred CD8+ T cells participated in the
      antiviral host response within a natural range and developed an effector
      phenotype indistinguishable from endogenous effector CD8+ T cells. Additionally,
      the generated reporter cell frequency allowed single cell visualization and
      tracking of a physiological antiretroviral CD8+ T cell response by intravital two
      photon microscopy. Highly reproducible results were obtained in independent
      experiments by reusing the same donors repetitively for multiple transfers. Our
      approach allows a strong reduction of experimental animals required for studies
      on antigen-specific CD8+ T cell function and should be applicable to other
      transfer models. KEY MESSAGES: TCRtg CD8+ T cells are obtained repetitively from
      the blood samples of single donors. One thousand transferred TCRtg CD8+ T cells
      get activated, are functional, and proliferate. Several adoptive cell transfers
      from the same donor show reproducible results. One thousand transferred cells
      take part in the FV immune response without modifying it. Use of fluorescent
      transfer cells allows in vivo imaging and single cell tracking.

PMID- 29460051
TI  - Brain STAT5 signaling modulates learning and memory formation.
AB  - The signal transducer and activator of transcription 5 (STAT5) is a transcription
      factor recruited by numerous cytokines. STAT5 is important for several
      physiological functions, including body and tissue growth, mammary gland
      development, immune system and lipid metabolism. However, the role of STAT5
      signaling for brain functions is still poorly investigated, especially regarding
      cognitive aspects. Therefore, the objective of the present study was to
      investigate whether brain STAT5 signaling modulates learning and memory
      formation. For this purpose, brain-specific STAT5 knockout (STAT5 KO) mice were
      studied in well-established memory tests. Initially, we confirmed a robust
      reduction in STAT5a and STAT5b mRNA levels in different brain structures of STAT5
      KO mice. STAT5 KO mice showed no significant alterations in metabolism, growth,
      somatotropic axis and spontaneous locomotor activity. In contrast, brain-specific
      STAT5 ablation impaired learning and memory formation in the novel object
      recognition, Barnes maze and contextual fear conditioning tests. To unravel
      possible mechanisms that might underlie the memory deficits of STAT5 KO mice, we
      assessed neurogenesis in the hippocampus, but no significant differences were
      observed between groups. On the other hand, reduced insulin-like growth factor-1
      (IGF-1) mRNA expression was found in the hippocampus and hypothalamus of STAT5 KO
      mice. These findings collectively indicate that brain STAT5 signaling is required
      to attain normal learning and memory. Therefore, STAT5 is an important downstream
      cellular mechanism shared by several cytokines to regulate cognitive functions.

PMID- 29460052
TI  - Dorsal raphe projection inhibits the excitatory inputs on lateral habenula and
      alleviates depressive behaviors in rats.
AB  - Hypofunction of the serotonergic (5-HT) system has close relationship with the
      symptoms in major depressive disorders (MDD), however, the underlying neural
      circuitry mechanisms are not fully understood. Lateral habenula (LHb) plays a
      crucial role in aversive behaviors and is activated in conditions of depression.
      It has been reported that 5-HT inhibits the excitability of LHb neurons, leading
      to the hypothesis that decreased transmission of 5-HT would elevate the activity
      of LHb and therefore mediates depressive symptoms. Using retrograde tract tracing
      with cholera toxin subunit B, we find that dorsal raphe nucleus (DRN) sends
      primary 5-HT projection to the LHb. In vitro slice patch-clamp recording reveals
      that opto-stimulation of DRN inputs to the LHb suppresses the frequency of
      miniature excitatory postsynaptic current, while increases paired pulse ratio in
      LHb neurons, indicating 5-HT projection presynaptically suppresses the
      excitability of LHb neurons. In chronic unpredictable mild stress (CUMS) rat
      model of depression, optogenetic stimulation of DRN-LHb projection alleviates the
      depressive symptoms in CUMS models. Meanwhile, opto-inhibition of this circuit
      results in elevated c-fos expression in LHb and induces depression-like
      behaviors. This study demonstrates that the 5-HT projection from DRN to LHb
      suppresses the excitability of LHb neurons, and hypofunction of 5-HT transmission
      induces depressive behavior via the activation of LHb. Our results reveal the
      functional connectivity of DRN-LHb circuit and its antidepressant action, which
      may provide a novel target for the treatment of depression.

PMID- 29460053
TI  - Extrasynaptic homomeric glycine receptors in neurons of the rat trigeminal
      mesencephalic nucleus.
AB  - The neurons in the trigeminal mesencephalic nucleus (Vmes) innervate jaw-closing
      muscle spindles and periodontal ligaments, and play a crucial role in the
      regulation of jaw movements. Recently, it was shown that many boutons that form
      synapses on them are immunopositive for glycine (Gly+), suggesting that these
      neurons receive glycinergic input. Information about the glycine receptors that
      mediate this input is needed to help understand the role of glycine in
      controlling Vmes neuron excitability. For this, we investigated the expression of
      glycine receptor subunit alpha 3 (GlyRalpha3) and gephyrin in neurons in Vmes and
      the trigeminal motor nucleus (Vmo), and the Gly+ boutons that contact them by
      light- and electron-microscopic immunocytochemistry and quantitative
      ultrastructural analysis. The somata of the Vmes neurons were immunostained for
      GlyRalpha3, but not gephyrin, indicating expression of homomeric GlyR. The
      immunostaining for GlyRalpha3 was localized away from the synapses in the Vmes
      neuron somata, in contrast to the Vmo neurons, where the staining for GlyRalpha3
      and gephyrin were localized at the subsynaptic zones in somata and dendrites.
      Additionally, the ultrastructural determinants of synaptic strength, bouton
      volume, mitochondrial volume, and active zone area, were significantly smaller in
      Gly+ boutons on the Vmes neurons than in those on the Vmo neurons. These findings
      support the notion that the Vmes neurons receive glycinergic input via putative
      extrasynaptic homomeric glycine receptors, likely mediating a slow, tonic
      modulation of the Vmes neuron excitability.

PMID- 29460054
TI  - Improved urethral fluorescence during low rectal surgery: a new dye and a new
      method.
AB  - BACKGROUND: The aim of this study was to demonstrate highlighting of the urethra
      during surgery through the use of two different methods: a new near-infrared
      fluorophore IRDye800BK, and indocyanine green (ICG) mixed with silicone. METHODS:
      Male cadavers from the department of anatomy at the University of Oxford were
      used to visualise the urethra during near-infrared fluorescence excitation. To
      assess IRDye800BK, a perineal incision was utilised after infiltrating the
      urethra directly with an IRDye800BK solution mixed with Instillagel. ICG-silicone
      was assessed when the urethra was purposely exposed as part of a simulated
      transanal total mesorectal dissection. ICG was previously mixed with ethanol and
      silicone and left to set in a Foley catheter. Fluorescence was visualised using
      an in-house manufactured fluorescence-enabled laparoscopic system. RESULTS:
      IRDye800BK demonstrated excellent penetration and visualisation of the urethra
      under fluorescence at an estimated tissue depth of 2 cm. An ICG-silicone catheter
      demonstrated excellent fluorescence without leaving any residual solution behind
      in the urethra after its removal. CONCLUSIONS: The newly described ICG-silicone
      method opens up the possibility of new technologies in this area of fluorescence
      guided surgery. IRDye800BK is a promising alternative to ICG in visualising the
      urethra using fluorescence imaging. Its greater depth of penetration may allow
      earlier detection of the urethra during surgery and prevent wrong plane surgery
      sooner.

PMID- 29460055
TI  - An assessment of the risk of element contamination of urban and industrial areas
      using Taraxacum sect. Ruderalia as a bioindicator.
AB  - Central Bohemia (Czech Republic) has highly developed industry and a dense rail
      network. Here, we aimed to determine the content of risk elements in dandelion
      plants (Taraxacum sect. Ruderalia) growing near train stations, industrial
      enterprises, and in the city parks of 16 cities in the Central Bohemian region.
      The highest element contents in the soils were found in industrial areas affected
      by the historical mining and smelting activities; contemporary industry showed no
      substantial effect on the soil element contents. The median values of element
      contents (As, Be, Cd, Co, Cr, Cu, Ni, Pb, and Zn) at the railway station sites
      were the highest among the monitored sites, where the differences between park
      and station sites were significant for Be, Co, and Zn. Although the intensity of
      the traffic at the individual stations differed, we found that long-term regular
      traffic enhanced the element contents in the soils and, subsequently, in the
      plants. For Cd, Co, Cr, Cu, Pb, V, and Zn, the highest median element contents
      were found in plant roots, regardless of the sampling site. For Cd and Zn, the
      contents in leaves were higher than in the inflorescences, and the opposite
      pattern was recorded for Co and Cu. As and Be were distributed equally among the
      plant parts. Among the sampling sites, the As, Be, Cd, Zn, and Pb contents in the
      plant roots tended to have higher median values at the station sites, confirming
      the results of our soil analyses. We detected a fairly good correlation between
      soil and plant content for cadmium, regardless of the sampling site, soil element
      content, or analyzed part of the plant. Thus, we propose that dandelion is a
      suitable bioindicator of cadmium pollution of soil.

PMID- 29460056
TI  - Testicular piRNA profile comparison between successful and unsuccessful micro
      TESE retrieval in NOA patients.
AB  - PURPOSE: PIWI-interacting RNA (piRNA) is a sub-group of small RNAs about 30
      nucleotides length which specifically expressed in mammalian germ cells. Although
      piRNAs play pivotal roles in spermatogenesis regulation, little is known in the
      testicular tissues of infertile men. To explore whether piRNA profile could serve
      as a biomarker for male infertility diagnosis in a clinic, in this study, we
      systematically investigated the expression profile of piRNAs in testicular
      tissues from the patients with non-obstructive azoospermia (NOA) between
      successful and unsuccessful sperm retrieval before micro-dissection testicular
      sperm extraction (micro-TESE). METHODS: The differential expression levels of
      piRNAs were evaluated using small RNA-Seq method. Ontologic analyses were
      performed to determine the presence of enriched biological processes. RESULTS: A
      total of 18,324 Homo sapiens piRNAs were identified by small RNA-Seq from NOA
      patient testicular tissues; among them, 959 piRNAs were significantly altered
      between successful and unsuccessful sperm retrieval groups, of which 951
      testicular piRNAs were significantly downregulated and 8 piRNAs were upregulated
      in NOA patients with unsuccessful sperm retrieval (USR) groups compared to those
      with successful sperm retrieval (SSR) groups, respectively. Unexpectedly, 553
      testicular piRNAs were found completely absent in USR but showing abundant in
      SSR, which suggests that those piRNAs might serve as a biomarker for micro-TESE
      application. A total of 20 significantly differential piRNAs (hsa-piR-20830, hsa
      piR-4731, hsa-piR-6254, hsa-piR-419, hsa-piR-7152, hsa-piR-7548, hsa-piR-14195,
      hsa-piR-5026, hsa-piR-11482, hsa-piR-17765, hsa-piR-17102, hsa-piR-4484, hsa-piR
      17260, hsa-piR-17098, hsa-piR-20511, hsa-piR-5802, hsa-piR-19121, hsa-piR-2510,
      hsa-piR-4745, hsa-piR-11873) were selected to further validate the RNA-Seq data
      by quantitative real-time polymerase chain reaction. In addition, bioinformatic
      analyses revealed that those altered piRNAs were involved in many important
      biological pathways, including apoptosis, cell proliferation, and
      differentiation. CONCLUSIONS: Our results demonstrate that testicular tissues
      from NOA patients with successful and unsuccessful spermatozoa retrieval exhibit
      differential piRNA profiles. This study provides a useful resource to further
      elucidate the regulatory role of piRNAs in spermatogenesis and provides a
      profound clue to identify useful biomarkers for predicting residual spermatogenic
      loci in NOA patients during assisted reproductive treatment.

PMID- 29460057
TI  - What happens after no contralateral exploration in total extraperitoneal (TEP)
      herniorrhaphy of clinical unilateral inguinal hernias?
AB  - BACKGROUND: While performing unilateral TEP herniorrhaphy, controversy still
      exists about whether to do contralateral exploration or not. Routine
      contralateral exploration has been proposed to prevent metachronous contralateral
      hernias by the repair of incidental contralateral occult hernias. Some surgeons
      have even proposed to do prophylactic bilateral TEP herniorrhaphy for unilateral
      hernia patients. To evaluate the appropriateness of not doing contralateral
      exploration in unilateral TEP herniorrhaphy, we reviewed our experiences under
      our practice of no contralateral exploration and we also reviewed other published
      literature. METHODS: A total of 305 patients who underwent 313 TEP
      herniorrhaphies for inguinal hernias by a single surgeon during August 2012-July
      2016 at Chia-Yi Christian Hospital were enrolled in this retrospective study.
      Demographic, perioperative and follow-up data were obtained for analysis and
      review. RESULTS: Of the 305 patients, 261 patients had unilateral TEP
      herniorrhaphy and 44 patients had bilateral TEP herniorrhaphy. The mean operation
      time for the unilateral TEP herniorrhaphy group was 59.8 min, and for the
      bilateral TEP herniorrhaphy group it was 85.2 min (p < 0.001). Seven of 261
      (2.7%) patients had metachronous contralateral hernia after unilateral TEP
      herniorrhaphy. There were no statistically significant differences in any of the
      outcome variables when comparing the sequential and simultaneous primary
      bilateral TEP herniorrhaphies. CONCLUSIONS: Without routine contralateral
      exploration, the incidence of metachronous contralateral hernia was 2.7% (7/261)
      in unilateral hernia patients. This is acceptable as metachronous hernia also
      occurred in 3.2% of patients with negative contralateral exploration according to
      our literature review. Sequential and simultaneous bilateral primary TEP
      herniorrhaphy outcomes were similar. We conclude that no exploration for the
      other groin is a justified decision for unilateral inguinal hernia patients.

PMID- 29460060
TI  - The establishment of Shanghai Pediatric Neurosurgical Society and the 12th Asian
      Australasian Advanced Course in Pediatric Neurosurgery (12th AAACPN): adventure
      and opportunity for Chinese pediatric neurosurgeons.

PMID- 29460058
TI  - The Immunologic Paradoxes of IgG4-Related Disease.
AB  - IgG4-related disease (IgG4-RD), which usually occurs in middle-aged and elderly
      men, is a newly recognized fibroinflammatory condition characterized by swelling
      and sclerosis of involved organs, increased IgG4-positive plasma cell
      infiltration in lesions, and elevated IgG4 concentration in serum. Despite
      growing interest in the research, the pathophysiological mechanism remains
      elusive. Most IgG4-RD patients respond well to steroid therapy initially, but
      recurrent and refractory cases are common, especially in advanced fibrotic stage.
      Recent studies have documented the heterogeneity of the B cell lineages, which
      suggests their multiple functions in IgG4-RD beyond IgG4 production, such as
      cytokine secretion, antigen presentation, autoantibody production, and modulation
      of T and B cell interactions. Thus, a critical balance exists between pathogenic
      and regulatory B subsets to prevent immunopathology. A prompt response to B cell
      depletion therapy reported in recent cases strongly suggests the imbalance within
      B cell lineages in IgG4-RD. A more precise understanding of the pathogenesis of
      IgG4-RD will open up new perspectives for therapeutic strategy. With a particular
      emphasis on the novel B cell-targeted therapeutic strategies, this review
      highlights the immunologic features of IgG4-RD and the possible roles of B cell
      lineages in the pathogenesis of IgG4-RD.

PMID- 29460059
TI  - Sublethal effects of insecticides used in soybean on the parasitoid Trichogramma
      pretiosum.
AB  - To control crop pests, parasitoid wasps of the genus Trichogramma are one
      alternative to the use of insecticides. Since a wide variety of agrochemicals may
      be applied to the same crops, it is essential to assess the selectivity of
      insecticides used for pest control on Trichogramma pretiosum. Information on
      which insecticides are less harmful to T. pretiosum can improve biological
      control using this insect, an important tactic in IPM programs for field crops.
      This study aimed to determine the effects of insecticides on the pupal stage and
      on the parasitism capacity of T. pretiosum. Lambda-cyhalothrin + thiamethoxam
      were slightly harmful and chlorpyriphos was moderately harmful to the pupal
      stage, while acephate, chlorfenapyr and flubendiamide, although considered
      innocuous, affected the succeeding generations of wasps, with low emergence of
      F1. Chlorfenapyr, chlorpyriphos and lambda-cyhalothrin + thiamethoxam reduced the
      parasitism, and acephate had a deleterious effect on the generation that
      contacted the insecticide residue. For an effective IPM program, it is important
      to apply selective insecticides. Further studies are needed to determine the
      selectivity of these insecticides under field conditions.

PMID- 29460061
TI  - Nondystrophic holocord intramedullary lipoma: an uncommon case.

PMID- 29460062
TI  - Non-syndromic single-suture craniosynostosis in triplets.
AB  - INTRODUCTION: Craniosynostosis is the premature fusion of one or more cranial
      sutures. The cause of non-syndromic craniosynostosis has been attributed to a
      complex interaction among genetic, epigenetic, and environmental factors.
      Increased concordance rates in monozygotic twins support a genetic etiology while
      a concordance rate less than 100% suggests environmental and/or epigenetic
      influences. Here, we describe the first reported occurrence of all three children
      in a triplet set with non-syndromic single-suture craniosynostosis. CASE REPORT:
      The dichorionic triamniotic triplets were the product of a non-consanguineous
      marriage delivered at 35 weeks' gestation by a 38-year-old mother and consisted
      of a monochorionic-diamniotic pair (A and B) and a fraternal triplet (C). Three
      dimensional computed tomography scans confirmed sagittal synostosis in A and B
      and metopic synostosis in C. All patients underwent endoscopic strip craniectomy
      and were discharged on the second postoperative day with helmet orthoses.
      Comparative genetic hybridization (CGH) and whole-exome sequencing (WES) failed
      to identify pathogenic copy number variants or gene mutations, respectively.
      DISCUSSION AND CONCLUSION: The results of the genetic testing suggest the
      possibility of a rare variant contributing to the risk of midline
      craniosynostosis shared among the triplets, with potential modifiers at other
      genetic loci affecting the phenotype. We speculate mutations at loci within non
      coding regions not captured by our genetic analysis may have been involved.
      Moreover, epigenetic factors as well as environmental factors including, but not
      limited to, in utero head constraint could have contributed to the observed
      phenotype.

PMID- 29460063
TI  - Virtual modeling, stereolithography, and intraoperative CT guidance for the
      optimization of sagittal synostosis reconstruction: a technical note.
AB  - INTRODUCTION: Sagittal synostosis affects 1 in 1000 live births and may result in
      increased intracranial pressure, hindrance of normal neural development, and
      cosmetic deformity due to scaphocephaly. Historically, several approaches have
      been utilized for surgical correction and recently, computed tomography (CT)
      guided reconstruction procedures are increasingly used. In this report, the
      authors describe the use of a CT-derived virtual and stereolithographic (3D
      printed) craniofacial models, which are used to guide intraoperative bone
      placement, and intraoperative CT guidance for confirmation of bone placement, to
      ensure the accuracy of surgical correction of scaphocephaly, as demonstrated to
      parents. METHODS: Preoperative high-resolution CT imaging was used to construct
      3D image sets of the skulls of two infants (a 14-month-old female and a 6-month
      old male) with scaphocephaly. These 3D image sets were then used to create a
      virtual model of the proposed surgical correction for each of the infants'
      deformities, which was then printed and made available for use intraoperatively
      to plan the bone flap, fashion the bone cuts, and optimize graft placement. After
      the remodeling, adherence to the preoperative plan was assessed by overlaying a
      CT scan of the remodeled skull with the virtual model. Deviations from the
      preoperative model were noted. RESULTS: Both patients had excellent postoperative
      cosmetic correction of head shape and contouring. The mean operative time was 5
      h, blood loss was 100 ml, and one child required modification of the subocciput
      after intraoperative imaging showed a deviation of the reconstruction from the
      surgical goal as depicted by the preoperative model. CONCLUSION: The addition of
      neuro-navigation to stereolithographic modeling ensured the accuracy of the
      reconstruction for our patients and provided greater confidence to both surgeons
      and parents. While unisutural cases are presented for clarity, correction was
      still required for one patient. The cost of the models and the additional CT
      required must be weighed against the complexity of the procedure and possibly
      reserved for patients with potentially complicated corrections.

PMID- 29460064
TI  - Our understanding and treatment of childhood hydrocephalus circa 1890 via
      Keating's Cyclopaedia of the Diseases of Children.

PMID- 29460065
TI  - The impact of intraoperative magnetic resonance in routine pediatric
      neurosurgical practice-a 6-year appraisal.
AB  - BACKGROUND: The intraoperative magnetic resonance scanner (ioMR) was introduced
      in our unit in 2009, and has been used routinely since then. OBJECTIVE: This
      study aims to describe indications, radiological features, and clinical outcomes
      of the patients operated on with ioMRI and analyze our experience. METHODS: A
      retrospective analysis of a prospective surgical database has been performed,
      including surgical procedure, intent, radiological reports, need for second-look
      surgery, and complications, supplemented by further review of the clinical notes
      and the scans. RESULTS: From 2009 to 2015, 255 surgical procedures with ioMR were
      performed: 175 were craniotomies for tumor excision, 65 were epilepsy related,
      and 15 were biopsies or cyst drainages. The mean age was 9.4 years. One ioMR was
      performed in 79.5% patients; the mean duration of the MR was 41 min. In 172 cases
      (67.4%), no actions followed the ioMR. When the aim of the surgery was debulking
      of the tumor, the percentage of patients in which the ioMR was followed by
      resection was higher than when complete resection was the aim (56 vs 27.5%). The
      complication rate was not increased when compared with our previous results
      (infection 1%, neurological deficits 12%). CONCLUSION: This is the largest
      published series of ioMRI-aided pediatric neurosurgery to date. We have
      demonstrated that it can be used safely and routinely in pediatric neurosurgical
      procedures at any age, assisting the surgeon in achieving the best extent of
      resection and aiding in intra-operative decision-making for tumor- and non-tumor
      related intracranial pathology.

PMID- 29460066
TI  - German Value Set for the EQ-5D-5L.
AB  - OBJECTIVES: The objective of this study was to develop a value set for EQ-5D-5L
      based on the societal preferences of the German population. As the first country
      to do so, the study design used the improved EQ-5D-5L valuation protocol 2.0
      developed by the EuroQol Group, including a feedback module as internal
      validation and a quality control process that was missing in the first wave of EQ
      5D-5L valuation studies. METHODS: A representative sample of the general German
      population (n = 1158) was interviewed using a composite time trade-off and a
      discrete choice experiment under close quality control. Econometric modeling was
      used to estimate values for all 3125 possible health states described by EQ-5D
      5L. The value set was based on a hybrid model including all available information
      from the composite time trade-off and discrete choice experiment valuations
      without any exclusions due to data issues. RESULTS: The final German value set
      was constructed from a combination of a conditional logit model for the discrete
      choice experiment data and a censored at -1 Tobit model for the composite time
      trade-off data, correcting for heteroskedasticity. The value set had logically
      consistent parameter estimates (p < 0.001 for all coefficients). The predicted EQ
      5D-5L index values ranged from -0.661 to 1. CONCLUSIONS: This study provided
      values for the health states of the German version of EQ-5D-5L representing the
      preferences of the German population. The study successfully employed for the
      first time worldwide the improved protocol 2.0. The value set enables the use of
      the EQ-5D-5L instrument in economic evaluations and in clinical studies.

PMID- 29460067
TI  - A Systematic Review of Physical Activity Interventions in Individuals with Binge
      Eating Disorders.
AB  - PURPOSE OF REVIEW: Our systematic review aims to assess the overall evidence
      available in the literature regarding the role of physical activity (PA) in
      individuals with binge eating disorder (BED) and better understand the potential
      underlying mechanisms of action. RECENT FINDINGS: Currently, the most effective
      and well-established psychological treatment for BED is cognitive behavioral
      therapy (CBT) with a remission rate around 80%. CBT is sometimes combined with
      pharmacotherapy targeting comorbidities associated with BED, such as obesity and
      depression. Another avenue of treatment that has been less studied is PA. It has
      been suggested that PA addresses the underlying mechanisms of BED and, thus,
      increases treatment efficiency. This systematic review provides additional
      knowledge concerning the benefits of PA in the treatment of individuals with BED
      including reduction of binge eating (BE) episodes and improvement in other
      associated comorbidities. Potential mechanisms of action of PA include
      neurochemical alterations affecting the reward system, reduction of negative
      affect, and its anorexigenic effects.

PMID- 29460068
TI  - Decanethiol functionalized silver nanoparticles are new powerful leishmanicidals
      in vitro.
AB  - We evaluated, for the first time, the leishmanicidal potential of decanethiol
      functionalized silver nanoparticles (AgNps-SCH) on promastigotes and amastigotes
      of different strains and species of Leishmania: L. mexicana and L. major isolated
      from different patients suffering from localized cutaneous leishmaniasis (CL) and
      L. mexicana isolated from a patient suffering from diffuse cutaneous
      leishmaniasis (DCL). We recorded the kinetics of promastigote growth by daily
      parasite counting for 5 days, promastigote mobility, parasite reproduction by
      CFSE staining's protocol and promastigote killing using the propidium iodide
      assay. We also recorded IC50's of promastigotes and amastigotes, therapeutic
      index, and cytotoxicity by co-culturing macrophages with AgNps-SCH or sodium
      stibogluconate (Sb) used as reference drug. We used Sb as a reference drug since
      it is used as the first line treatment for all different types of leishmaniasis.
      At concentrations 10,000 times lower than those used with Sb, AgNps-SCH had a
      remarkable leishmanicidal effect in all tested strains of parasites and there was
      no toxicity to J774A.1 macrophages since > 85% were viable at the concentrations
      used. Therapeutic index was about 20,000 fold greater than the corresponding one
      for Sb treated cells. AgNps-SCH inhibited > 80% promastigote proliferation in all
      tested parasites. These results demonstrate there is a high leishmanicidal
      potential of AgNps-SCH at concentrations of 0.04 uM. Although more studies are
      needed, including in vivo testing of AgNps-SCH against different types of
      leishmaniasis, they can be considered a potential new treatment alternative.

PMID- 29460069
TI  - Experimental feasibility of spectral photon-counting computed tomography with two
      contrast agents for the detection of endoleaks following endovascular aortic
      repair.
AB  - OBJECTIVES: After endovascular aortic repair (EVAR), discrimination of endoleaks
      and intra-aneurysmatic calcifications within the aneurysm often requires
      multiphase computed tomography (CT). Spectral photon-counting CT (SPCCT) in
      combination with a two-contrast agent injection protocol may provide reliable
      detection of endoleaks with a single CT acquisition. METHODS: To evaluate the
      feasibility of SPCCT, the stent-lined compartment of an abdominal aortic aneurysm
      phantom was filled with a mixture of iodine and gadolinium mimicking enhanced
      blood. To represent endoleaks of different flow rates, the adjacent compartments
      contained either one of the contrast agents or calcium chloride to mimic intra
      aneurysmatic calcifications. After data acquisition with a SPCCT prototype
      scanner with multi-energy bins, material decomposition was performed to generate
      iodine, gadolinium and calcium maps. RESULTS: In a conventional CT slice,
      Hounsfield units (HU) of the compartments were similar ranging from 147 to 168
      HU. Material-specific maps differentiate the distributions within the
      compartments filled with iodine, gadolinium or calcium. CONCLUSION: SPCCT may
      replace multiphase CT to detect endoleaks without sacrificing diagnostic
      accuracy. It is a unique feature of our method to capture endoleak dynamics and
      allow reliable distinction from intra-aneurysmatic calcifications in a single
      scan, thereby enabling a significant reduction of radiation exposure. KEY POINTS:
      * SPCCT might enable advanced endoleak detection. * Material maps derived from
      SPCCT can differentiate iodine, gadolinium and calcium. * SPCCT may potentially
      reduce radiation burden for EVAR patients under post-interventional surveillance.

PMID- 29460070
TI  - Comparison of image quality and radiation dose between split-filter dual-energy
      images and single-energy images in single-source abdominal CT.
AB  - OBJECTIVES: To compare image quality and radiation dose of abdominal split-filter
      dual-energy CT (SF-DECT) combined with monoenergetic imaging to single-energy CT
      (SECT) with automatic tube voltage selection (ATVS). METHODS: Two-hundred single
      source abdominal CT scans were performed as SECT with ATVS (n = 100) and SF-DECT
      (n = 100). SF-DECT scans were reconstructed and subdivided into composed images
      (SF-CI) and monoenergetic images at 55 keV (SF-MI). Objective and subjective
      image quality were compared among single-energy images (SEI), SF-CI and SF-MI.
      CNR and FOM were separately calculated for the liver (e.g. CNRliv) and the portal
      vein (CNRpv). Radiation dose was compared using size-specific dose estimate
      (SSDE). Results of the three groups were compared using non-parametric tests.
      RESULTS: Image noise of SF-CI was 18% lower compared to SEI and 48% lower
      compared to SF-MI (p < 0.001). Composed images yielded higher CNRliv over single
      energy images (23.4 vs. 20.9; p < 0.001), whereas CNRpv was significantly lower
      (3.5 vs. 5.2; p < 0.001). Monoenergetic images overcame this inferiority in CNRpv
      and achieved similar results compared to single-energy images (5.1 vs. 5.2; p >
      0.628). Subjective sharpness was equal between single-energy and monoenergetic
      images and diagnostic confidence was equal between single-energy and composed
      images. FOMliv was highest for SF-CI. FOMpv was equal for SEI and SF-MI (p =
      0.78). SSDE was significant lower for SF-DECT compared to SECT (p < 0.022).
      CONCLUSIONS: The combined use of split-filter dual-energy CT images provides
      comparable objective and subjective image quality at lower radiation dose
      compared to single-energy CT with ATVS. KEY POINTS: * Split-filter dual-energy
      results in 18% lower noise compared to single-energy with ATVS. * Split-filter
      dual-energy results in 11% lower SSDE compared to single-energy with ATVS. *
      Spectral shaping of split-filter dual-energy leads to an increased dose
      efficiency.

PMID- 29460071
TI  - Transjugular intrahepatic portosystemic shunt creation: three-dimensional roadmap
      versus CO2 wedged hepatic venography.
AB  - OBJECTIVES: The blind portal vein puncture remains the most challenging step
      during transjugular intrahepatic portosystemic shunt (TIPS) creation. We
      performed a prospective randomised clinical trial to compare three-dimensional
      (3D) roadmap with CO2 wedged hepatic vein portography for portal vein puncture
      guidance. METHODS: Between March 2017 and May 2017, 30 patients were enrolled and
      randomly allocated to the study group (3D roadmap) or the control group (CO2
      wedged hepatic vein portography). RESULTS: Technical success of TIPS procedures
      was achieved in all 30 patients. The mean number of needle passes was
      significantly lower in the study group (2.0 +/- 1.0) compared to the control
      group (3.7 +/- 2.5; p = 0.021). A total of six (40%) patients in the study group
      and three (20%) in the control group required only one puncture for the
      establishment of TIPS. There were no significant differences in total fluoroscopy
      time (p = 0.905), total procedure time (p = 0.199) and dose-area product (p =
      0.870) between the two groups. CONCLUSIONS: 3D roadmap is a safe and technically
      feasible means for portal vein puncture guidance during TIPS creation, equivalent
      in efficacy to CO2 wedged hepatic vein portography. This technique could reduce
      the number of needle passes, thereby simplifying the TIPS procedure. KEY POINTS:
      * 3D roadmap can be used to guide portal vein puncture. * Compared with CO 2
      venography, 3D roadmap reduced the number of needle passes. * 3D roadmap has a
      potential to simplify the TIPS procedure.

PMID- 29460072
TI  - New MRI muscle classification systems and associations with return to sport after
      acute hamstring injuries: a prospective study.
AB  - OBJECTIVES: To determine agreement between modified Peetrons, Chan acute muscle
      strain injury classification and British Athletics Muscle Injury Classification
      (BAMIC) and to investigate their associations and ability to predict time to
      return to sport (RTS). METHODS: Male athletes (n=176) with acute hamstring injury
      and MRI (1.5T) <=5 days were followed until RTS. MRIs were scored using
      standardised forms. RESULTS: For MRI-positive injuries there was moderate
      agreement in severity grading (kappa = 0.50-0.56). Substantial variance in RTS
      was demonstrated within and between MRI categories. Mean differences showed an
      overall main effect for severity grading (p < 0.001), but post hoc pairwise
      comparisons for BAMIC (grade 0a/b vs. 1, p = 0.312; 1 vs 2, p = 0.054; 0a/b vs 2,
      p < 0.001; 1 vs 3, p < 0.001) and mean differences for anatomical sites (BAMIC a
      c, p < 0.001 [a vs b, p = 0.974; a vs c, p = 0.065; b vs c, p = 0.007]; Chan
      anatomical sites 1-5, p < 0.077; 2A-C, p = 0.373; 2a-e, p = 0.008; combined
      BAMIC, p < 0.001) varied. For MRI-positive injuries, total explained RTS variance
      was 7.6-11.9% for severity grading and BAMIC anatomical sites. CONCLUSIONS: There
      was wide overlap between/variation within the grading/classification categories.
      Therefore, none of the classification systems could be used to predict RTS in our
      sample of MRI-positive hamstring injuries. KEY POINTS: * Days to RTS varied
      greatly within the grading and classification categories. * Days to RTS varied
      greatly between the grading and classification categories. * Using MRI
      classification systems alone to predict RTS cannot be recommended. * The specific
      MRI classification used should be reported to avoid miscommunication.

PMID- 29460073
TI  - Progressive supranuclear palsy and idiopathic Parkinson's disease are associated
      with local reduction of in vivo brain viscoelasticity.
AB  - OBJECTIVES: To apply three-dimensional multifrequency MR-elastography (3DMRE) for
      the measurement of local cerebral viscoelasticity changes in patients with
      Parkinson's disease (PD) and progressive supranuclear palsy (PSP). METHODS: T1
      weighted anatomical imaging and 3DMRE were performed in 17 PD and 20 PSP patients
      as well as 12 controls. Two independent viscoelasticity parameters, |G*| and phi,
      were reconstructed combining seven harmonic vibration frequencies (30-60 Hz).
      Spatially averaged values were compared by one-way ANOVA, groups were compared
      using unpaired t test and Mann-Whitney test, respectively. Correlation between
      clinical data and parameters of brain elasticity and volume were calculated by
      Pearson's correlation coefficient. RESULTS: In patients, |G*| was significantly
      reduced in the frontal and mesencephalic regions (p < 0.05). Beyond that, reduced
      mesencephalic |G*| discriminated PSP from PD (p < 0.05). Neurodegeneration causes
      significant brain atrophy (p < 0.01) and is pronounced in PSP patients (p < 0.05
      vs. PD). Reduced brain viscoelasticity is correlated with brain atrophy in PSP
      (r=0.64, p=0.002) and PD (r=0.65, p=0.005) patients but not in controls.
      CONCLUSIONS: MRE-measured viscoelasticity reflects local structural changes of
      brain tissue in PSP and in PD and provides a useful parameter to differentiate
      neurodegenerative movement disorders based on imaging examinations. KEY POINTS: *
      3D multifrequency MR-elastography reveals diffuse regional changes in brain
      viscoelasticity in neurodegenerative disorders. * Reduced mesencephalic
      viscoelasticity separates PD and PSP. * Reduced brain viscoelasticity and brain
      atrophy as independent hallmarks of neurodegeneration hypothesized.

PMID- 29460074
TI  - The role of breast tomosynthesis in a predominantly dense breast population at a
      tertiary breast centre: breast density assessment and diagnostic performance in
      comparison with MRI.
AB  - OBJECTIVES: To compare breast density measured on digital breast tomosynthesis
      (DBT) (BI-RADS-based breast composition and fully-automatic estimation) and
      magnetic resonance imaging (MRI) (BI-RADS amount of fibroglandular tissue), and
      to evaluate the diagnostic performance in terms of sensitivity and specificity of
      DBT and MRI in a predominantly dense breast population. METHODS: Between 2015 and
      2016, 152 women with 103 breast malignancies, who underwent 3-T breast MRI and
      DBT within 2 months' time, were enrolled in this study. Breast
      composition/fibroglandular tissue and findings on DBT (two readers) and MRI were
      reported using BI-RADS 5th edition. Digital mammography images were analysed for
      breast percent density (PD) using the Libra software tool. RESULTS: A majority of
      women had dense breasts as categorised by breast composition c (heterogeneously
      dense) (68%) and d (extremely dense) (15%). The mean PD was 44% (range, 18-89%)
      and the correlation between breast composition and PD was r = 0.6. The diagnostic
      performance of MRI was significantly higher compared to DBT for one reader as
      described by the area under the receiver operating characteristic (ROC) curve (p
      = 0.004) and of borderline significance for the other reader (p = 0.052).
      CONCLUSIONS: MRI had higher diagnostic performance than DBT in a dense breast
      population in the tertiary setting. KEY POINTS: * MRI had higher diagnostic
      performance than DBT in a dense breast population * Diagnostic performance of DBT
      was comparable to MRI in women with fatty breasts * MRI was superior to DBT in
      preoperative breast cancer size assessment.

PMID- 29460075
TI  - A noise-optimized virtual monoenergetic reconstruction algorithm improves the
      diagnostic accuracy of late hepatic arterial phase dual-energy CT for the
      detection of hypervascular liver lesions.
AB  - OBJECTIVES: To assess the image quality and diagnostic accuracy of a noise
      optimized virtual monoenergetic imaging (VMI+) algorithm compared with standard
      virtual monoenergetic imaging (VMI) and linearly-blended (M_0.6) reconstructions
      for the detection of hypervascular liver lesions in dual-energy CT (DECT).
      METHODS: Thirty patients who underwent clinical liver MRI were prospectively
      enrolled. Within 60 days of MRI, arterial phase DECT images were acquired on a
      third-generation dual-source CT and reconstructed with M_0.6, VMI and VMI+
      algorithms from 40 to 100 keV in 5-keV intervals. Liver parenchyma and lesion
      contrast-to-noise-ratios (CNR) were calculated. Two radiologists assessed image
      quality. Lesion sensitivity, specificity and area under the receiver operating
      characteristic curves (AUCs) were calculated for the three algorithms with MRI as
      the reference standard. RESULTS: VMI+ datasets from 40 to 60 keV provided the
      highest liver parenchyma and lesion CNR (p <=0.021); 50 keV VMI+ provided the
      highest subjective image quality (4.40+/-0.54), significantly higher compared to
      VMI and M_0.6 (all p <0.001), and the best diagnostic accuracy in < 1-cm diameter
      lesions (AUC=0.833 vs. 0.777 and 0.749, respectively; p <=0.003). CONCLUSIONS: 50
      keV VMI+ provides superior image quality and diagnostic accuracy for the
      detection of hypervascular liver lesions with a diameter < 1cm compared to VMI or
      M_0.6 reconstructions. KEY POINTS: * Low-keV VMI+ are characterized by higher
      contrast resulting from maximum iodine attenuation. * VMI+ provides superior
      image quality compared with VMI or M_0.6. * 50-keV_VMI+ provides higher accuracy
      for the detection of hypervascular liver lesions < 1cm.

PMID- 29460077
TI  - Orofacial antinociceptive effect of sulphated polysaccharide from the marine
      algae Hypnea pseudomusciformis in rodents.
AB  - This study aimed to evaluate the antinociceptive effect of sulphated
      polysaccharide from the marine algae Hypnea pseudomusciformis (PLS) using rodent
      models of orofacial pain. Acute pain was induced by formalin, capsaicin,
      cinnamaldehyde, acidified saline or glutamate (cutaneous modes) and hypertonic
      saline (corneal model). In one experiment, animals were pretreated with ruthenium
      red, glibenclamide, naloxone, L-NAME, methylene blue or ketamine to investigate
      the mechanism of antinociception. In another experiment, animals pretreated with
      PLS or saline were submitted to the temporomandibular joint formalin test. In yet
      another, animals were submitted to craniofacial pain induced by mustard oil.
      Motor activity was evaluated with the open-field test. Cytotoxicity and
      antioxidant activities were also assessed. Pre-treatment with PLS significantly
      reduced nociceptive behavior associated with acute pain. Antinociception was
      effectively reduced, but not inhibited, by ruthenium red and ketamine. L-NAME and
      glibenclamide enhanced the PLS effect. PLS antinociception was resistant to
      methylene blue, naloxone and heating. PLS presented no cytotoxicity or
      antioxidant properties. Our results confirm the potential pharmacological
      relevance of PLS as an inhibitor of orofacial nociception in acute pain probably
      mediated by glutamatergic, nitrergic, TRPs and K + ATP pathways.

PMID- 29460076
TI  - Visual grading analysis of digital neonatal chest phantom X-ray images: Impact of
      detector type, dose and image processing on image quality.
AB  - OBJECTIVES: To evaluate the impact of digital detector, dose level and post
      processing on neonatal chest phantom X-ray image quality (IQ). METHODS: A
      neonatal phantom was imaged using four different detectors: a CR powder phosphor
      (PIP), a CR needle phosphor (NIP) and two wireless CsI DR detectors (DXD and
      DRX). Five different dose levels were studied for each detector and two post
      processing algorithms evaluated for each vendor. Three paediatric radiologists
      scored the images using European quality criteria plus additional questions on
      vascular lines, noise and disease simulation. Visual grading characteristics and
      ordinal regression statistics were used to evaluate the effect of detector type,
      post-processing and dose on VGA score (VGAS). RESULTS: No significant differences
      were found between the NIP, DXD and CRX detectors (p>0.05) whereas the PIP
      detector had significantly lower VGAS (p< 0.0001). Processing did not influence
      VGAS (p=0.819). Increasing dose resulted in significantly higher VGAS (p<0.0001).
      Visual grading analysis (VGA) identified a detector air kerma/image (DAK/image)
      of ~2.4 MUGy as an ideal working point for NIP, DXD and DRX detectors.
      CONCLUSIONS: VGAS tracked IQ differences between detectors and dose levels but
      not image post-processing changes. VGA showed a DAK/image value above which
      perceived IQ did not improve, potentially useful for commissioning. KEY POINTS: *
      A VGA study detects IQ differences between detectors and dose levels. * The NIP
      detector matched the VGAS of the CsI DR detectors. * VGA data are useful in
      setting initial detector air kerma level. * Differences in NNPS were consistent
      with changes in VGAS.

PMID- 29460078
TI  - Labisia pumila prevented osteoarthritis cartilage degeneration by attenuating
      joint inflammation and collagen breakdown in postmenopausal rat model.
AB  - The tropical herb Labisia pumila is traditionally used in facilitating childbirth
      and post-partum care. The effects of L. pumila leaf extract (LP) in explant
      cartilage culture and on postmenopausal osteoarthritis (OA) rat model were
      assessed. The LP (10, 25 and 50 ug/ml) or diclofenac (10 ug/ml) was added to the
      cartilage explants containing bovine IL-1beta (20 ng/ml), to evaluate their
      direct effects on cartilage degradation. In the preclinical study, rats were
      grouped (n = 8) into: non-treated OA; OA + diclofenac (5 mg/kg); OA + LP extract
      (150 and 300 mg/kg); and healthy control. To induce OA, monosodium iodoacetate
      was injected into the ovariectomised female rats' intra-articular knee joints and
      evaluated for OA severity after 8 weeks via physical (radiological, macroscopic
      and histological observations), biochemical, ELISA and mRNA expression analysis
      (for inflammation and cartilage degradation biomarkers). The LP reduced the
      nitric oxide and proteoglycan release from the cartilage explants under IL-1beta
      induction. The radiological, macroscopic, microscopic and histological images
      showed the OA rats treated with LP and diclofenac had significantly reduced
      osteophytes and cartilage erosions compared to non-treated OA rats. The extract
      significantly up-regulated the anti-inflammatory interleukin-10, collagen type II
      and down-regulated pro-inflammatory PTGS2 (prostaglandin-endoperoxide synthase 2)
      mRNA expressions compared to non-treated control. The LP treatment significantly
      reduced serum collagenases (MMP-1 and MMP-3) and collagen type II degradation
      biomarker (CTX-II) levels in OA rats. The LP containing myricetin and gallic acid
      suppressed inflammation, collagenases and cartilage degradation, and helped
      cartilage matrix synthesis, to prevent OA at the dose equivalent to 30-60 mg/kg
      daily for humans.

PMID- 29460079
TI  - The Biological Contributions to Gender Identity and Gender Diversity: Bringing
      Data to the Table.
AB  - The American Psychological Association defines gender identity as, "A person's
      deeply-felt, inherent sense of being a boy, a man, or a male; a girl, a woman, or
      a female; or an alternative gender (e.g., genderqueer, gender nonconforming,
      gender neutral) that may or may not correspond to a person's sex assigned at
      birth or to a person's primary or secondary sex characteristics" (American
      Psychological Association, Am Psychol 70(9):832-864, 2015). Here we review the
      evidence that gender identity and related socially defined gender constructs are
      influenced in part by innate factors including genes. Based on the data reviewed,
      we hypothesize that gender identity is a multifactorial complex trait with a
      heritable polygenic component. We argue that increasing the awareness of the
      biological diversity underlying gender identity development is relevant to all
      domains of social, medical, and neuroscience research and foundational for
      reducing health disparities and promoting human-rights protections for gender
      minorities.

PMID- 29460080
TI  - Heterogeneity of gestational diabetes (GDM) and long-term risk of diabetes and
      metabolic syndrome: findings from the RADIEL study follow-up.
AB  - AIMS: To assess the metabolic health of obese and non-obese women at high GDM
      risk 5 years postpartum. METHODS: This is a secondary analysis of the 5-year
      follow-up of the RADIEL GDM prevention study including 333 women at high GDM risk
      (BMI >= 30 kg/m2 and/or previous GDM). Five years postpartum metabolic health was
      assessed including anthropometric measurements, oral glucose tolerance test,
      lipid metabolism, and body composition as well as medical history questionnaires.
      For the analysis, we divided the women into four groups based on parity, BMI, and
      previous history of GDM. RESULTS: Five years postpartum impaired glucose
      regulation (IFG, IGT, or diabetes) was diagnosed in 15% of the women; 3.6% had
      type 2 diabetes. The highest prevalence was observed among obese women with a
      history of GDM (26%), and the lowest prevalence (8%) among primiparous obese
      women (p = 0.021). At follow-up 25-39% of the obese women fulfilled the
      diagnostic criteria for the metabolic syndrome, in the non-obese group 11% (p <
      0.001). This was associated with body fat percentage. The non-obese group,
      however, faced metabolic disturbances (IFG, IGT, diabetes, or metabolic syndrome)
      at a significantly lower BMI (p < 0.001). Among women who were non-obese before
      pregnancy, 5 years postpartum, the obesity prevalence based on BMI was 14% and
      based on body fat percentage 58%. CONCLUSIONS: The prevalence of impaired glucose
      regulation and metabolic syndrome is high 5 years postpartum among women at high
      risk of GDM. There are high-risk women also among the non-obese, who develop
      metabolic derangements already at a lower BMI. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, www.clinicaltrials.com , NCT01698385.

PMID- 29460081
TI  - Critiquing the Reasons for Making Artificial Moral Agents.
AB  - Many industry leaders and academics from the field of machine ethics would have
      us believe that the inevitability of robots coming to have a larger role in our
      lives demands that robots be endowed with moral reasoning capabilities. Robots
      endowed in this way may be referred to as artificial moral agents (AMA). Reasons
      often given for developing AMAs are: the prevention of harm, the necessity for
      public trust, the prevention of immoral use, such machines are better moral
      reasoners than humans, and building these machines would lead to a better
      understanding of human morality. Although some scholars have challenged the very
      initiative to develop AMAs, what is currently missing from the debate is a closer
      examination of the reasons offered by machine ethicists to justify the
      development of AMAs. This closer examination is especially needed because of the
      amount of funding currently being allocated to the development of AMAs (from
      funders like Elon Musk) coupled with the amount of attention researchers and
      industry leaders receive in the media for their efforts in this direction. The
      stakes in this debate are high because moral robots would make demands on
      society; answers to a host of pending questions about what counts as an AMA and
      whether they are morally responsible for their behavior or not. This paper shifts
      the burden of proof back to the machine ethicists demanding that they give good
      reasons to build AMAs. The paper argues that until this is done, the development
      of commercially available AMAs should not proceed further.

PMID- 29460082
TI  - Testing Hypotheses on Risk Factors for Scientific Misconduct via Matched-Control
      Analysis of Papers Containing Problematic Image Duplications.
AB  - It is commonly hypothesized that scientists are more likely to engage in data
      falsification and fabrication when they are subject to pressures to publish, when
      they are not restrained by forms of social control, when they work in countries
      lacking policies to tackle scientific misconduct, and when they are male.
      Evidence to test these hypotheses, however, is inconclusive due to the
      difficulties of obtaining unbiased data. Here we report a pre-registered test of
      these four hypotheses, conducted on papers that were identified in a previous
      study as containing problematic image duplications through a systematic screening
      of the journal PLoS ONE. Image duplications were classified into three categories
      based on their complexity, with category 1 being most likely to reflect
      unintentional error and category 3 being most likely to reflect intentional
      fabrication. We tested multiple parameters connected to the hypotheses above with
      a matched-control paradigm, by collecting two controls for each paper containing
      duplications. Category 1 duplications were mostly not associated with any of the
      parameters tested, as was predicted based on the assumption that these
      duplications were mostly not due to misconduct. Categories 2 and 3, however,
      exhibited numerous statistically significant associations. Results of univariable
      and multivariable analyses support the hypotheses that academic culture, peer
      control, cash-based publication incentives and national misconduct policies might
      affect scientific integrity. No clear support was found for the "pressures to
      publish" hypothesis. Female authors were found to be equally likely to publish
      duplicated images compared to males. Country-level parameters generally exhibited
      stronger effects than individual-level parameters, because developing countries
      were significantly more likely to produce problematic image duplications. This
      suggests that promoting good research practices in all countries should be a
      priority for the international research integrity agenda.

PMID- 29460083
TI  - Kidney function and use of nonsteroidal anti-inflammatory drugs among elderly
      people: a cross-sectional study on potential hazards for an at risk population.
AB  - : Background Renal elimination normally decreases with age. Nonsteroidal
      antiinflammatory drugs (NSAIDs) carry a risk of additional kidney damage.
      Objective The aims of this study were to assess the prevalence of NSAIDs in the
      elderly (aged >= 65) population in Sweden, explore reasons for any possible
      differences in the level of use and assess their kidney functions. Setting Data
      were obtained from the cohort study Good Aging in Skane, Sweden. Patients aged 65
      or more were included. Methods Medication lists were collected as well as
      variables such as cognition and education levels. Glomerular filtration rate was
      estimated from creatinine and cystatin C. Descriptive statistics and multiple
      linear regression analysis were used. MAIN OUTCOME MEASURE: NSAID use among the
      general elderly population. Results A total of 1798 patients were included.
      Approximately six percent (n = 105) of the people in the study group were using
      NSAIDs and of those 82 (78%) bought NSAIDs over the counter (OTC). 42% of those
      buying NSAIDs OTC showed an estimated glomerular filtration rate below 60
      ml/min/1.73 m2. Education level did not affect the use of nonsteroidal anti
      inflammatory drugs, nor did age. NSAIDs were more commonly used than other
      recommended analgesics. Conclusion Many people are unaware of the risks
      associated with the use of NSAIDs. The findings imply that the frailest elderly
      use NSAIDs to the same extent as the younger elderly do. It is important that
      information about safety of these drugs be communicated to both patients and
      healthcare professionals.

PMID- 29460084
TI  - Persistent Organic Pollutants Residues in Human Breast Milk from Bathinda and
      Ludhiana Districts of Punjab, India.
AB  - In the present study, persistent organic pollutants (POPs), including six
      congeners of polychlorinated biphenyls (PCBs) and organochlorine pesticides, were
      estimated in human breast milk samples collected from two districts of Punjab
      (India). The mean concentrations of POP residues were recorded higher in Bathinda
      district (PCBs: 33.7; DDTs: 519.2; HCHs: 46.6 ng g-1 lipid wt.) than Ludhiana
      (PCBs: 24.2; DDTs; 415.3; HCHs; 35.5 ng g-1 lipid wt.). Levels of PCBs and DDTs
      were observed higher in primiparas, whereas HCHs residues were seen more in
      multiparas. Risk analysis to POPs exposure through breast milk reflected that the
      daily intake for some infants was close to or above the tolerable daily intake
      limit for detrimental effects, which may raise a health concern. Comparative
      evaluation of present data indicated that DDT and HCHs residue levels in human
      breast milk from Punjab, India were among the lowest values reported for
      developing countries. The first-order kinetic reaction at a steady-state
      condition used to estimate the half-life of DDT and HCH suggested that DDT levels
      have declined from 18,211 to 490 ng g-1 lipid wt. with a half-life (Tdec1/2) of
      3.25 years over a span of 15 years. Similarly, HCH levels have decreased from
      8609 to 46.6 ng g-1 in this duration with Tdec1/2 of 2.25 years. Because some
      infants are still at risk, continuous monitoring of POPs in human milk is needed
      for surveillance and interpretation of time trends and for linkage to strict
      enforcement of agricultural regulations.

PMID- 29460085
TI  - Bioaccumulation Study of Produced Water Discharges from Southeastern Brazilian
      Offshore Petroleum Industry Using Feral Fishes.
AB  - The main effluent of oil and gas production is the discharge of produced water
      (PW). Despite the potential environmental impact, the structure of oil and gas
      platforms can act as artificial reefs. Two species of fish, Caranx crysos and
      Tylosurus acus, were captured under two discharging platforms at Campos Basin,
      P19 and P40. A nondischarging platform, P25, was taken as reference. The highest
      median concentration of PAH in muscle tissue was observed for C. Crysos at P40
      (219.38 ng g-1) followed by P19 (68.26 ng g-1). For T. acus, the highest median
      concentrations were 40.07 and 42.21 ng g-1 from P19 and P40 respectively. P25
      presented the smallest recorded concentrations. The results of PAH in the muscle
      tissue of C. crysos enabled to distinguish the platforms with PW discharge from
      the platform without discharge. Trace elements concentrations reflected the
      background levels and were not influenced by the PW release.

PMID- 29460086
TI  - Systematic Analysis of Primary Sequence Domain Segments for the Discrimination
      Between Class C GPCR Subtypes.
AB  - G-protein-coupled receptors (GPCRs) are a large and diverse super-family of
      eukaryotic cell membrane proteins that play an important physiological role as
      transmitters of extracellular signal. In this paper, we investigate Class C, a
      member of this super-family that has attracted much attention in pharmacology.
      The limited knowledge about the complete 3D crystal structure of Class C
      receptors makes necessary the use of their primary amino acid sequences for
      analytical purposes. Here, we provide a systematic analysis of distinct receptor
      sequence segments with regard to their ability to differentiate between seven
      class C GPCR subtypes according to their topological location in the
      extracellular, transmembrane, or intracellular domains. We build on the results
      from the previous research that provided preliminary evidence of the potential
      use of separated domains of complete class C GPCR sequences as the basis for
      subtype classification. The use of the extracellular N-terminus domain alone was
      shown to result in a minor decrease in subtype discrimination in comparison with
      the complete sequence, despite discarding much of the sequence information. In
      this paper, we describe the use of Support Vector Machine-based classification
      models to evaluate the subtype-discriminating capacity of the specific
      topological sequence segments.

PMID- 29460087
TI  - Prescription Changes During Geriatric Care Episodes: A Trend Analysis Conducted
      in Sweden.
AB  - BACKGROUND: The number of drugs prescribed for old people has been rising in
      recent decades. With increasing age and multiple medications, the risk of
      complications and drug prescription complexity increases. Multiple changes to
      prescriptions could be a factor that improves treatment quality. OBJECTIVES: Our
      objective was to investigate trends in drug prescriptions and factors that
      contribute to prescription changes. Specific objectives were to find out whether
      high numbers of prescription changes are significantly correlated with age, sex,
      comorbidity, length of care episode, and number of drugs. METHODS: Data were
      extracted from geriatric clinic records in Stockholm in 2005, 2010, and 2015.
      Indicators for good drug therapy were used to assess the effects of prescription
      changes on quality, using an index of inappropriate drug use (IDU). Data were
      analyzed with Student's t-test, PR test, Wilcoxon's rank sum test, and linear
      regression. RESULTS: Patients had more comorbidities and used more drugs but had
      shorter hospital stays and significantly fewer prescription changes in 2015 than
      in 2005. Length of care episode was significantly associated with prevalence of
      prescription changes. Our model showed that, for each day by which the length of
      care episode decreased, the number of prescription changes decreased by 8%. The
      number of prescription changes was negatively correlated to the IDU index score.
      CONCLUSIONS: The study showed that more prescription changes were associated with
      longer care episodes and improved drug prescribing quality as per the IDU index.
      Given prescription changes are regarded as a quality factor in geriatric care,
      quality may have decreased along with the length of care episodes between 2005
      and 2015.

PMID- 29460088
TI  - Vascular deficiency of Smad4 causes arteriovenous malformations: a mouse model of
      Hereditary Hemorrhagic Telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular
      disorder that leads to abnormal connections between arteries and veins termed
      arteriovenous malformations (AVM). Mutations in TGFbeta pathway members ALK1, ENG
      and SMAD4 lead to HHT. However, a Smad4 mouse model of HHT does not currently
      exist. We aimed to create and characterize a Smad4 endothelial cell (EC)
      specific, inducible knockout mouse (Smad4f/f;Cdh5-CreERT2) that could be used to
      study AVM development in HHT. We found that postnatal ablation of Smad4 caused
      various vascular defects, including the formation of distinct AVMs in the neonate
      retina. Our analyses demonstrated that increased EC proliferation and size,
      altered mural cell coverage and distorted artery-vein gene expression are
      associated with Smad4 deficiency in the vasculature. Furthermore, we show that
      depletion of Smad4 leads to decreased Vegfr2 expression, and concurrent loss of
      endothelial Smad4 and Vegfr2 in vivo leads to AVM enlargement. Our work provides
      a new model in which to study HHT-associated phenotypes and links the TGFbeta and
      VEGF signaling pathways in AVM pathogenesis.

PMID- 29460089
TI  - Competing nomograms help in the selection of elderly patients with colon cancer
      for adjuvant chemotherapy.
AB  - PURPOSE: The extent to which >= 70 year patients with colon cancer benefit from
      adjuvant chemotherapy in the presence of competing risks remains controversial.
      METHODS: 18,937 patients >= 70 years with high-risk stage II and stage III colon
      cancer were retrospectively reviewed from SEER database. Propensity score
      matching (PSM) was used to adjust for potential baseline confounding. The
      nomograms were developed based on the competing model to describe the individual
      probability of colon cancer-specific death (CCSD) and non-CCSD. The subpopulation
      treatment-effect pattern plot (STEPP) was used to estimate the treatment-effect
      heterogeneity. RESULTS: In the high-risk stage II subgroup, compared to the non
      recipients, the hazard ratios (HR) of overall mortality for recipients were 0.83
      (P = 0.001). The subdistribution hazard ratio (SHR) of CCSD for receipts was 1.22
      (P = 0.021). The SHR of non-CCSD was 0.63 (P < 0.001). In the stage III subgroup,
      compared to non-recipients, the HR of the overall mortality for the recipients
      was 0.62 (P < 0.001). The SHR of CCSD was 0.77 (P < 0.001). The SHR of non-CCSD
      was 0.58 (P < 0.001). The chemotherapy efficacy differed significantly by risk
      score of non-CCSD (non-CCSD-RS) (P < 0.001). Recipients with high non-CCSD-RS had
      a rate of CCSD comparative to that of non-recipients (SHR 0.90, P = 0.150) in the
      stage III subgroup. CONCLUSIONS: A survival analysis based on the overall
      mortality did not correctly interpret the effect of chemotherapy. Adjuvant
      chemotherapy did not provide an additional benefit to patients with high-risk
      stage II or patients with stage III at high risk of non-cancer death.

PMID- 29460090
TI  - Medical Big Data Warehouse: Architecture and System Design, a Case Study:
      Improving Healthcare Resources Distribution.
AB  - The huge increases in medical devices and clinical applications which generate
      enormous data have raised a big issue in managing, processing, and mining this
      massive amount of data. Indeed, traditional data warehousing frameworks can not
      be effective when managing the volume, variety, and velocity of current medical
      applications. As a result, several data warehouses face many issues over medical
      data and many challenges need to be addressed. New solutions have emerged and
      Hadoop is one of the best examples, it can be used to process these streams of
      medical data. However, without an efficient system design and architecture, these
      performances will not be significant and valuable for medical managers. In this
      paper, we provide a short review of the literature about research issues of
      traditional data warehouses and we present some important Hadoop-based data
      warehouses. In addition, a Hadoop-based architecture and a conceptual data model
      for designing medical Big Data warehouse are given. In our case study, we provide
      implementation detail of big data warehouse based on the proposed architecture
      and data model in the Apache Hadoop platform to ensure an optimal allocation of
      health resources.

PMID- 29460091
TI  - Factors in Removing Job Restrictions for Cancer Survivors in the United Kingdom
      Royal Air Force.
AB  - Purpose To identify personal, occupational and clinical factors associated with
      the lifting of restrictions on duties among Royal Air Force (RAF) personnel who
      have returned to work after surviving primary cancer treatment. Methods A
      retrospective cohort of 205 RAF personnel aged 18-58 with cancer diagnosed
      between 2001 and 2011 was followed-up until May 2012. Personal, occupational, and
      clinical information was extracted from occupational health and primary care
      records. Predictors of the lifting of (a) employment restrictions on UK duties at
      18 months after diagnosis and (b) the lifting of all deployment restrictions at
      the end of the study were analysed using logistic and Cox regression models.
      Results At 18 months, 62% of the cancer survivors had restrictions on their UK
      duties lifted. The positive independent predictors of unrestricted UK duties are
      testicular cancer (OR 5.34; 95% CI 1.21-23.6) and no treatment being required
      (16.8; 1.11-255.2). The lifting of all employment restrictions and return to full
      deployability was achieved by 41% of the participants (median time 2.1 years),
      with testicular cancer (HR 2.69; 95% CI 1.38-5.26) and age at diagnosis (1.05;
      1.01-1.09) being the positive independent predictors of faster lifting of all
      restrictions. Conclusion Diagnostic group, prognosis and type of treatment are
      not the only predictor of employment outcome after cancer. Patient-centred
      factors such as smoking, age, fatigue, job status, job type and length of
      employment are also important predictors of return to pre-morbid job function in
      cancer survivors in the RAF.

PMID- 29460093
TI  - Vitamin D testing: finding a balance.

PMID- 29460092
TI  - Balancing in- and out-breeding by the predatory mite Phytoseiulus persimilis.
AB  - In- and out-breeding depressions are commonly observed phenomena in sexually
      reproducing organisms with a patchy distribution pattern, and spatial
      segmentation and/or isolation of groups. At the genetic level, inbreeding
      depression is due to increased homozygosity, whereas outbreeding depression is
      due to inferior genetic compatibility of mates. Optimal outbreeding theory
      suggests that intermediate levels of mate relatedness should provide for the
      highest fitness gains. Here, we assessed the fitness consequences of genetic
      relatedness between mates in plant-inhabiting predatory mites Phytoseiulus
      persimilis, which are obligatory sexually reproducing but haplo-diploid. Both
      females and males arise from fertilized eggs but males lose the paternal
      chromosome set during embryogenesis, dubbed pseudo-arrhenotoky. Phytoseiulus
      persimilis are highly efficacious in reducing crop-damaging spider mite
      populations and widely used in biological control. Using iso-female lines of two
      populations, from Sicily and Greece, we assessed the fecundity of females, and
      sex ratio of their offspring, that mated with either a sibling, a male from the
      same population or a male from the other population. Additionally, we recorded
      mating latency and duration. Females mating with a male from the same population
      produced more eggs, with a lower female bias, over a longer time than females
      mating with a sibling or with a male from the other population. Mating latency
      was unaffected by mate relatedness; mating duration was disproportionally long in
      sibling couples, likely indicating female reluctance to mate and sub-optimal
      spermatophore transfer. Our study provides a rare example of in- and out-breeding
      depression in a haplo-diploid arthropod, supporting the optimal outbreeding
      theory.

PMID- 29460094
TI  - Ear, nose and throat involvement in granulomatosis with polyangiitis: how it
      presents and how it determines disease severity and long-term outcomes.
AB  - Ear, nose and throat (ENT) manifestations in granulomatosis with polyangiitis
      (GPA) represent the most frequent symptoms at disease onset. The aim of the study
      was to analyse ENT involvement at diagnosis, as well as how it could influence
      relapse rate, mortality and disease severity. A retrospective non-controlled
      cohort study was performed including all consecutive diagnosed GPA from 1996 to
      2016 in two rheumatology centres of Northern Italy, focusing particularly on ENT
      presenting signs and symptoms at baseline. Eighty-nine patients (48.3% females)
      with new onset GPA were evaluated. They were mostly Caucasian (97.7%), middle
      aged (mean 54.5 years) and more frequently anti-neutrophil cytoplasmic antibodies
      (ANCA) positive (78.6%) with PR3 specificity (81.4%). At diagnosis, ENT
      involvement was reported in 71.9% patients, second only to systemic symptoms.
      These patients were significantly younger at disease onset (0.013), with less
      frequent renal involvement (0.014) irrespectively to ANCA status, but with
      significantly higher Vasculitis Damage Index (VDI) (0.001). The most frequent ENT
      manifestation was sinonasal involvement (58.4%, 73% of which with nasal
      inflammation/chronic sinusitis and 48% with nasal crusting), while otologic
      involvement (mainly otitis media/otomastoiditis) was observed in 34.8%. ENT-GPA
      patients presented a higher survival rate at 5 years (98.1 vs 77.7%, 0.049), and
      ENT involvement resulted to be an independent predictor of better outcome (OR
      0.37, 95% CI 0.2-0.8, 0.019). Our data confirms that ENT involvement is not only
      one of the key clinical features of GPA, but also could point out a milder GPA
      subset with lower renal involvement and lower mortality rate, irrespectively to
      ANCA status.

PMID- 29460095
TI  - Diagnosis, characteristics, and treatment of breast carcinomas within benign
      fibroepithelial tumors.
AB  - BACKGROUND: Breast carcinoma arising in a benign fibroepithelial tumor is rare,
      and is usually discovered incidentally during examination of the breast mass.
      METHODS: We evaluated the clinicopathological features, treatment, and prognosis
      of seven women with breast carcinomas within benign fibroepithelial tumors,
      diagnosed and treated at a single institution between 2011 and 2015. RESULTS:
      Seven women, aged 21-64 years, visited our hospital complaining of a breast mass
      detected by self-checking or screening examination. All patients had well
      demarcated movable breast masses. Ultrasonography showed circumscribed masses
      suggesting benign tumors in all cases, and mammography revealed well-defined,
      high-density masses, with or without calcification. The masses progressed in two
      patients. A preoperative histological diagnosis of carcinoma was made following
      needle biopsy in four patients. Tumorectomy, breast-conserving surgery, and
      mastectomy were performed in three, two, and two patients, respectively. One
      patient underwent lymph node dissection and another underwent sentinel node
      biopsy. Histologically, the masses were diagnosed as invasive ductal carcinoma,
      ductal carcinoma in situ or lobular carcinoma in situ, arising in a benign
      phyllodes tumor, fibroadenoma, or fibroadenomatoid mastopathy. Lymph node
      metastasis was detected in two patients. There was no recurrence in any of the
      patients. CONCLUSIONS: Although a carcinoma within a preexisting benign
      fibroepithelial tumor is extremely rare, it is important to be aware of the
      possibility of invasive and metastatic disease.

PMID- 29460096
TI  - Body mass index and age at natural menopause: an international pooled analysis of
      11 prospective studies.
AB  - Current evidence on the association between body mass index (BMI) and age at
      menopause remains unclear. We investigated the relationship between BMI and age
      at menopause using data from 11 prospective studies. A total of 24,196 women who
      experienced menopause after recruitment was included. Baseline BMI was
      categorised according to the WHO criteria. Age at menopause, confirmed by natural
      cessation of menses for >= 12 months, was categorised as < 45 years (early
      menopause), 45-49, 50-51 (reference category), 52-53, 54-55, and >= 56 years
      (late age at menopause). We used multinomial logistic regression models to
      estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals
      (CI) for the associations between BMI and age at menopause. The mean (standard
      deviation) age at menopause was 51.4 (3.3) years, with 2.5% of the women having
      early and 8.1% late menopause. Compared with those with normal BMI (18.5-24.9
      kg/m2), underweight women were at a higher risk of early menopause (RRR 2.15, 95%
      CI 1.50-3.06), while overweight (1.52, 1.31-1.77) and obese women (1.54, 1.18
      2.01) were at increased risk of late menopause. Overweight and obesity were also
      significantly associated with around 20% increased risk of menopause at ages 52
      53 and 54-55 years. We observed no association between underweight and late
      menopause. The risk of early menopause was higher among obese women albeit not
      significant (1.23, 0.89-1.71). Underweight women had over twice the risk of
      experiencing early menopause, while overweight and obese women had over 50%
      higher risk of experiencing late menopause.

PMID- 29460097
TI  - Prognostic role of high sensitivity C-reactive protein and interleukin-6 in
      glioma and meningioma patients.
AB  - High sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) can be
      important prognostic indicators of brain tumor patients. We investigated the
      association of circulating IL-6 and hsCRP concentrations with discharge outcomes
      and survival of glioma and meningioma patients. One-hundred and sixty-three (115
      women; median age 57 years) patients admitted for meningioma (n = 94), high-grade
      glioma (n = 48) and low-grade glioma (n = 21) surgery were enrolled in this
      prospective cohort study. Serum samples were collected within 24 h of admission.
      Discharge outcome was evaluated using the Glasgow Outcome Scale (unfavorable
      outcome = score from 1 to 3). Follow-up continued until November, 2016. Elevated
      IL-6 (>= 2 pg/ml) and hsCRP (>= 1 mg/l) concentrations were present in 25 and 35%
      of brain tumor patients, respectively. Elevated IL-6 concentrations were
      associated with unfavorable outcome at hospital discharge, adjusting for brain
      tumor histological diagnosis, patient age and gender (OR 2.39, 95% CI 0.97-5.91,
      p = 0.05). Elevated hsCRP concentrations were not associated with discharge
      outcome (p = 0.13). In multivariate Cox regression analyses adjusted for patient
      age, gender, extent of tumor resection and adjuvant treatment, elevated IL-6
      concentration was associated with greater mortality risk in high-grade glioma
      patients (OR 2.623; 95% CI 1.129-5.597; p = 0.01), while elevated hsCRP
      concentration was associated with greater mortality risk in meningioma patients
      (OR 3.650; 95% CI 1.038-12.831; p = 0.04). Elevated IL-6 concentration is
      associated with greater unfavorable outcome risk in brain tumor patients and with
      greater mortality in high-grade glioma patients, while elevated hsCRP
      concentration is associated with greater mortality in meningioma patients.

PMID- 29460099
TI  - R0: Host Longevity Matters.
AB  - The basic reproduction ratio, R0, is a fundamental concept in epidemiology. It is
      defined as the total number of secondary infections brought on by a single
      primary infection, in a totally susceptible population. The value of R0 indicates
      whether a starting epidemic reaches a considerable part of the population and
      causes a lot of damage, or whether it remains restricted to a relatively small
      number of individuals. To calculate R0 one has to evaluate an integral that
      ranges over the duration of the infection of the host. This duration is, of
      course, limited by remaining host longevity. So, R0 depends on remaining host
      longevity and in this paper we show that for long-lived hosts this aspect may not
      be ignored for long-lasting infections. We investigate in particular how this
      epidemiological measure of pathogen fitness depends on host longevity. For our
      analyses we adopt and combine a generic within- and between-host model from the
      literature. To find the optimal strategy for a pathogen from an evolutionary
      point of view, we focus on the indicator [Formula: see text], i.e., the optimum
      of R0 as a function of its replication and mutation rates. These are the within
      host parameters that the pathogen has at its disposal to optimize its strategy.
      We show that [Formula: see text] is highly influenced by remaining host longevity
      in combination with the contact rate between hosts in a susceptible population.
      In addition, these two parameters determine whether a killer-like or a milker
      like strategy is optimal for a given pathogen. In the killer-like strategy the
      pathogen has a high rate of reproduction within the host in a short time span
      causing a relatively short disease, whereas in the milker-like strategy the
      pathogen multiplies relatively slowly, producing a continuous small amount of
      offspring over time with a small effect on host health. The present research
      allows for the determination of a bifurcation line in the plane of host longevity
      versus contact rate that forms the boundary between the milker-like and killer
      like regions. This plot shows that for short remaining host longevities the
      killer-like strategy is optimal, whereas for very long remaining host longevities
      the milker-like strategy is advantageous. For in-between values of host
      longevity, the contact rate determines which of both strategies is optimal.

PMID- 29460100
TI  - The effect of magnesium on early osseointegration in osteoporotic bone: a
      histological and gene expression investigation: response to comments by Marcus.

PMID- 29460101
TI  - Pulse-echo ultrasound method for detection of post-menopausal women with
      osteoporotic BMD.
AB  - : We lack effective diagnostics of osteoporosis at the primary health care level.
      An ultrasound device was used to identify subjects in the osteoporotic range as
      defined by DXA. A case finding strategy combining ultrasound results with DXA
      measurements for patients with intermediate ultrasound results is presented.
      INTRODUCTION: We lack effective screening and diagnostics of osteoporosis at
      primary health care. In this study, a pulse-echo ultrasound (US) method is
      investigated for osteoporosis screening. METHODS: A total of 1091 Caucasian women
      (aged 50-80 years) were recruited for the study and measured with US in the tibia
      and radius. This method measures cortical thickness and provides an estimate of
      bone mineral density (BMD) and density index (DI). BMD assessment of the hip was
      available for 988 women. A total of 888 women had one or more risk factors for
      osteoporosis (OP susp ), and 100 women were classified healthy. Previously
      determined thresholds for the DI were evaluated for assessment of efficacy of the
      technique to detect hip BMD at osteoporotic range (T-score at or below - 2.5).
      RESULTS: In the OP susp group, the application of thresholds for the DI showed
      that approximately 32% of the subjects would require an additional DXA
      measurement. The multi-site ultrasound (US) measurement-based DI showed 93.7%
      sensitivity and 81.6% specificity, whereas the corresponding values for single
      site US measurement-based DI were 84.7 and 82.0%, respectively. The ultrasound
      measurements showed a high negative predictive value 97.7 to 99.2% in every age
      decade examined (ages 50-59, 60-69, 70-79 years). CONCLUSIONS: The study data
      demonstrate that a strategy of combining ultrasound measurement with added DXA
      measurements in cases with intermediate ultrasound results (about 30%) can be
      useful for identifying subjects at risk for a low bone mineral density in the
      osteoporotic range.

PMID- 29460102
TI  - Economic impact and cost-effectiveness of fracture liaison services: a systematic
      review of the literature.
AB  - Fracture liaison services (FLS), implemented in different ways and countries, are
      reported to be a cost-effective or even a cost-saving secondary fracture
      prevention strategy. This presumed favorable cost-benefit relationship is
      encouraging and lends support to expanded implementation of FLS per International
      Osteoporosis Foundation Best Practice Standards. This study summarizes the
      economic impact and cost-effectiveness of FLS implemented to reduce subsequent
      fractures in individuals with osteoporosis. This systematic review identified
      studies reporting economic outcomes for FLS in osteoporotic patients aged 50 and
      older through a comprehensive search of MEDLINE, EMBASE, Cochrane Central, and
      PubMed of studies published January, 2000 to December, 2016. Grey literature
      (e.g., Google scholar, conference abstracts/posters) were also hand searched
      through February 2017. Two independent reviewers screened titles and abstracts
      and conducted full-text review on qualified articles. All disagreements were
      resolved by discussion between reviewers to reach consensus or by a third
      reviewer. In total, 23 qualified studies that evaluated the economic aspects of
      FLS were included: 16 cost-effectiveness studies, 2 cost-benefit analyses, and 5
      studies of cost savings. Patient populations varied (prior fragility fracture,
      non-vertebral fracture, hip fracture, wrist fracture), and FLS strategies ranged
      from mail-based interventions to comprehensive nurse/physician-coordinated
      programs. Cost-effectiveness studies were conducted in Canada, Australia, USA,
      UK, Japan, Taiwan, and Sweden. FLS was cost-effective in comparisons with usual
      care or no treatment, regardless of the program intensity or the country in which
      the FLS was implemented (cost/QALY from $3023-$28,800 US dollars (USD) in Japan
      to $14,513-$112,877 USD in USA. Several studies documented cost savings. FLS,
      implemented in different ways and countries, are reported to be cost-effective or
      even cost-saving. This presumed favorable cost-benefit relationship is
      encouraging and lends support to expanded implementation of FLS per International
      Osteoporosis Foundation Best Practice Standards.

PMID- 29460103
TI  - Parkinson's disease and the risk of osteoporotic vertebral compression fracture:
      a nationwide population-based study.
AB  - : Patients with Parkinson's disease (PD) were at higher risk of osteoporotic
      vertebral compression fractures (OVCF) compared to controls and had elevated
      mortality rates. Compared to conservative treatment, surgical treatment for OVCF
      in PD patients seemed to be associated with better outcomes. INTRODUCTION: The
      purpose of this study was to evaluate the risk of OVCF in patients with PD.
      METHODS: Data from patients over the age of 60 years who were diagnosed with PD
      were collected between 2004 and 2013 from the Korean National Health Insurance
      Database (n = 3370). The comparison group (non-PD) consisted of randomly selected
      patients (five per patient with PD; n = 16,850) matched to the PD group, who were
      newly diagnosed annually according to age and sex. Cox proportional hazard
      regressions were used to examine the relationships between osteoporosis, OVCF,
      surgery for OVCF, and PD. Household income and residential area of patients were
      also assessed. Overall survival rates were calculated after adjusting for
      confounding factors, such as hypertension, diabetes mellitus, and chronic kidney
      disease. RESULTS: OVCF was developed in 12.5% of patients in the PD group and in
      7.4% of patients in the control group. PD was associated with increased risk of
      osteoporosis (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.21-1.43; p
      < 0.001), OVCF (HR 1.66; 95% CI, 1.47-1.87; p < 0.001), and surgery for OVCF (HR
      2.69; 95% CI, 1.78-4.08; p < 0.001). Household income was not significantly
      related with development of osteoporosis, incidence of OVCF, or surgery for OVCF.
      Residential area was statistically associated with osteoporosis, OVCF, and
      surgery for OVCF. The mortality rate of the PD group was about 1.7 times higher
      than that of the non-PD group after adjusting for potential confounders, and the
      mortality rate of the PD with OVCF group was higher than that of the non-PD
      group, but not significantly (p = 0.09). The survival rate of the PD group with
      surgery for OVCF showed a trend toward a more positive prognosis compared with
      that of the PD group with conservative treatment. CONCLUSIONS: Patients with PD
      had significantly increased risk of osteoporosis and OVCF. Surgical treatment for
      OVCF in PD patients was associated with a better prognosis than conservative
      treatment.

PMID- 29460104
TI  - Comments on Galli et al.: The effect of magnesium on early osseointegration in
      osteoporotic bone: a histological and gene expression investigation.

PMID- 29460105
TI  - The importance of standardisation of measurement and reference intervals for
      detection of phaeochromocytoma and paraganglioma (PPGL).
AB  - A 51-year-old male presented 25 years ago with excessive sweating and haematuria.
      Blood pressure was labile. CT abdomen showed a large right-sided adrenal mass.
      Two 24-h urine collections showed elevated urinary catecholamines. Right adrenal
      resection was performed; a phaeochromocytoma (PC) was confirmed histologically.
      Two decades later, the patient represented with excessive sweating and measured
      variable blood pressure readings. Measurement of plasma metanephrines (PMets)
      showed elevated normetanephrine (NMN) [50,250 (R.I. 0-1180) pmol/L] and
      metanephrine (MN) [1030 (R.I. 0-510) pmol/L] values. CT abdomen showed a 100 * 90
      * 63 mm enhancing mass in the right retroperitoneum. Curative resection was
      undertaken confirming recurrent PC. Follow-up post-resection, plasma NMN was
      discordant, 1314 pmol/L (above decision threshold) at 30 min and 911 pmol/L
      (below decision threshold) at 40 min. Acute clinical awareness of persistent
      disease mandated the performance of a metaiodobenzylguanidine (MIBG) scan and CT
      abdomen. These confirmed residual disease in the upper right side of the
      retroperitoneum. Persistent disease following redo surgery could have been missed
      if only seated-sampling upper reference limits were applied to PMets collected at
      40 min. Our experience with this patient triggered a review of our PMets sampling
      strategy. There was no statistically significant difference in PMets sampled at
      30 and at 40 min seated-rest. Optimum diagnostic test accuracy was achieved using
      a supine-sampling strategy at a single time point (30 min). Our case highlights
      the importance of maintaining a high index of clinical suspicion for
      residual/recurrent disease in the face of inconclusive biochemistry, followed by
      appropriate targeted radiology using MIBG or PET-CT in patients with PPGL.

PMID- 29460106
TI  - Assessment of Chronic Illness-Related Cognitive Fusion: Preliminary Development
      and Validation of a New Scale with an IBD Sample.
AB  - Although research recognizes the advantages of creating specific content
      measures, no specific measure of chronic illness-related cognitive fusion had
      been developed to date. The current study presents the development and validation
      of the Cognitive Fusion Questionnaire-Chronic Illness (CFQ-CI) in a sample of
      inflammatory bowel disease (IBD) patients and the analysis of the role of this
      construct in the psychological health of those patients. Results indicated that
      the 7-item CFQ-CI was a unidimensional measure of cognitive fusion in patients
      with chronic illnesses, and that scores had adequate/good internal consistency
      and construct, convergent, and discriminant validity. This study also showed that
      chronic illness-related cognitive fusion as assessed by the CFQ-CI acted as a
      mediator in the association between both IBD-related symptoms and shame with
      quality of life. The development of the CFQ-CI may thus contribute to a better
      understanding of the mechanisms influencing functional outcomes in chronic
      illness.

PMID- 29460107
TI  - Assessing Psychiatric Symptoms in Youth Affected by HIV: Comparing a Brief Self
      Administered Rating Scale with a Structured Diagnostic Interview.
AB  - Brief psychiatric assessment tools are needed for evaluating children affected by
      HIV for emotional and behavioral problems. We compared a self-administered
      symptom rating scale (CASI-4R) to a semi-structured diagnostic interview (DICA-P)
      in 136 U.S. children affected by HIV. Agreement and performance measures for the
      two instruments were computed for attention deficit hyperactivity disorder,
      depression, anxiety, and disruptive behavior. Correlations and regression
      analyses were conducted to compare the two instruments, and to evaluate their
      associations with social, academic, and global function. Higher CASI-4R symptom
      severity scores were associated with DICA diagnoses (p < 0.02 for all disorders).
      Agreement (kappa) between DICA diagnoses and CASI-4R Clinical Cutoffs (which
      incorporated symptoms and impairment) was low to moderate (0.19-0.40 for all
      disorders). Thirty-two percent of cases with a DICA diagnosis were identified by
      the CASI-4R Clinical Cutoff (sensitivity), yet over 90% of DICA-negative cases
      were negative by the CASI-4R (specificity). Sensitivity was higher using CASI-4R
      Severity Score thresholds based on median scores compared to the DICA diagnoses.
      The presence and severity of psychiatric symptoms and impairment were associated
      with poorer academic, social, and global function. The CASI-4R symptom checklist
      can be used to inexpensively screen youth affected by HIV for emotional and
      behavioral problems, although it is important that there be appropriate mental
      health evaluation follow-up.

PMID- 29460108
TI  - Stressors increase leptin receptor-expressing thymic epithelial cells in the
      infant/child thymus.
AB  - The thymus, the organ that is the most sensitive to stress, presents acute
      involution as a result of exposure to strong stress in childhood. Thymic
      involution is thus often considered evidence of child abuse/neglect in forensic
      autopsies. A portion of the thymic epithelial cells express leptin receptor, and
      leptin showed a thymo-protective function against stress-induced thymic
      involution in an animal model. Leptin receptor-expressing thymic epithelial cells
      (LR-TECs) may play a key role in the thymic remodeling provoked by a stressful
      environment. Here, we sought to clarify the changes of histopathological findings
      and human LR-TECs in stressful environment. We examined human thymus specimens
      obtained from 40 forensic autopsy cases (26 male, 14 female; age 21 to 3221
      days). We divided the cases into stressor-positive (SP, n = 29) and stressor
      negative (SN, n = 11) groups. Cases were classified according to the histological
      classification of thymic involution and investigated by leptin receptor
      immunostaining. The results revealed that (1) the SP group showed obvious
      histological thymic involution (p < 0.01) and (2) the LR-TECs/TECs ratio in the
      cortex was markedly and significantly increased in the SP group compared to the
      SN group (p < 0.01). The increase in the cortical LR-TECs/TECs ratio in the SP
      group may be part of the stress response mechanism in the human thymus. We thus
      speculate that the quantification of LR-TECs in the thymic cortex is a valuable
      stress marker for forensic autopsy cases.

PMID- 29460109
TI  - Online selling of wildlife part with spurious name: a serious challenge for
      wildlife crime enforcement.
AB  - We examined an online sold product "Hatha Jodi" synonym of "paired arm" for the
      confirmation of its biological source. It was declared as a plant root. The
      morphological features of these samples were matched with the "intromittent
      organs" or "hemi penis" of the monitor lizard. For further confirmation, we used
      sequencing of a partial fragment of mitochondrial DNA cytochrome b gene. Sequence
      comparison indicated that these claimed plant products were actually biological
      samples of a common monitor lizard, Varanus bengalensis. Hence, it exhibited the
      ongoing illegal trade of the intromittent organ of a prohibited species with a
      misleading name using low risk and widely adopted modern trading method that
      imposes a severe challenge for combating against the wildlife crime.

PMID- 29460112
TI  - Association between oral contraceptives and risk of hemorrhagic stroke: a meta
      analysis of observational studies.
AB  - OBJECTIVES: To estimate the risk of hemorrhagic stroke associated with current
      use of oral contraceptives (OCs), and to further depict how the risk was affected
      by study characteristics. METHODS: We searched PubMed, Embase, and Cochrane
      Library for relevant articles published up to February 2017 that examined the
      association between OC use and risk of hemorrhagic stroke. Two investigators
      independently reviewed articles based on inclusion criteria. The Newcastle-Ottawa
      scale was employed to evaluate quality of studies. Random-effects meta-analysis
      model was used to generate summary risk estimates. RESULTS: Fifteen independent
      studies (5 cohort studies and 10 case-control studies) with 4271 hemorrhagic
      stroke cases were included in this meta-analysis. The overall summary odds ratio
      (OR) for hemorrhagic stroke (HS) in relation to current OC use was 1.39 [95%
      confidence interval (CI), 1.05-1.83]. Subgroup analyses on hemorrhagic stroke
      types showed that OC use was associated with subarachnoid hemorrhage (SAH) (OR
      1.68; 95% CI 1.21-2.12), but not with intracerebral hemorrhage (ICH) (OR 0.92;
      95% CI 0.33-2.54). The risk of hemorrhagic stroke was increased slightly among
      current OC users with high-dose estrogen (OR 1.60; 95% CI 1.12-2.27). The risk of
      hemorrhagic stroke was further increased in OC users with additional risk factors
      including current smoking, hypertension, and history of migraine. CONCLUSIONS:
      This meta-analysis of observational studies suggests that current use of OCs
      could contribute to a small increased risk of hemorrhagic stroke, and the
      increased risk is related to subarachnoid hemorrhage, but not intracerebral
      hemorrhage.

PMID- 29460111
TI  - The Changing Age of Individuals Seeking Presymptomatic Genetic Testing for
      Huntington Disease.
AB  - Huntington disease (HD) is a progressive neurodegenerative disorder.
      Presymptomatic genetic testing allows at-risk individuals to clarify their risk
      status. Understanding the characteristics and motivations of individuals seeking
      HD presymptomatic genetic testing better equips genetic counselors and other
      healthcare professionals to provide comprehensive and personalized care. The aims
      of this study were to (1) determine whether the average age when individuals seek
      presymptomatic HD genetic testing has decreased over time, (2) assess motivations
      for seeking testing, (3) explore whether there is a relationship between age and
      motivations, and (4) explore genetic counselors' perceptions of the shift in age.
      Data from the US HD testing centers (N = 4) were analyzed. A small but
      statistically significant decrease in age of individuals seeking presymptomatic
      testing was observed (p = 0.045). HD community members (N = 77) were surveyed
      regarding presymptomatic testing motivations. Younger individuals were more
      likely than older individuals to cite "To learn whether or not you would develop
      HD" and "To make choices about further education or a career" compared to older
      individuals (p < 0.05). Conversely, older individuals more frequently cited "To
      give children a better idea of their risk" (p < 0.002). Sixteen percent of
      genetic counselors surveyed (6/37) perceived a change in age of testing. All of
      these respondents had provided HD testing for ten or more years and anecdotally
      believed the age at testing has decreased over time. Study results help providers
      personalize counseling based on patient's age and serve as a starting point for
      more research into the relationship between age at testing and motivations for
      testing.

PMID- 29460110
TI  - Operationalizing the Reciprocal Engagement Model of Genetic Counseling Practice:
      a Framework for the Scalable Delivery of Genomic Counseling and Testing.
AB  - With the advent of widespread genomic testing for diagnostic indications and
      disease risk assessment, there is increased need to optimize genetic counseling
      services to support the scalable delivery of precision medicine. Here, we
      describe how we operationalized the reciprocal engagement model of genetic
      counseling practice to develop a framework of counseling components and
      strategies for the delivery of genomic results. This framework was constructed
      based upon qualitative research with patients receiving genomic counseling
      following online receipt of potentially actionable complex disease and
      pharmacogenomics reports. Consultation with a transdisciplinary group of
      investigators, including practicing genetic counselors, was sought to ensure
      broad scope and applicability of these strategies for use with any large-scale
      genomic testing effort. We preserve the provision of pre-test education and
      informed consent as established in Mendelian/single-gene disease genetic
      counseling practice. Following receipt of genomic results, patients are afforded
      the opportunity to tailor the counseling agenda by selecting the specific test
      results they wish to discuss, specifying questions for discussion, and indicating
      their preference for counseling modality. The genetic counselor uses these
      patient preferences to set the genomic counseling session and to personalize
      result communication and risk reduction recommendations. Tailored visual aids and
      result summary reports divide areas of risk (genetic variant, family history,
      lifestyle) for each disease to facilitate discussion of multiple disease risks.
      Post-counseling, session summary reports are actively routed to both the patient
      and their physician team to encourage review and follow-up. Given the breadth of
      genomic information potentially resulting from genomic testing, this framework is
      put forth as a starting point to meet the need for scalable genetic counseling
      services in the delivery of precision medicine.

PMID- 29460113
TI  - Transcriptome-Wide Identification of Differentially Expressed Genes and Long Non
      coding RNAs in Aluminum-Treated Rat Hippocampus.
AB  - Aluminum (Al) is an environmental neurotoxicant with a wide exposure, but the
      molecular mechanism underlying its toxicity remains unclear. We used RNA
      sequencing (RNA-seq) in the hippocampus of Al-treated rats to identify 96
      upregulated and 652 downregulated mRNAs, and 37 dysregulated long non-coding
      (lnc)RNAs. Gene ontology analysis showed that dysregulated genes were involved in
      glial cell differentiation, neural transmission, and vesicle trafficking. Kyoto
      Encyclopedia of Genes and Genomes pathway analysis revealed clustering of
      differentially expressed mRNAs and lncRNA target genes in several pathways,
      including the "adenosine monophosphate-activated protein kinase signaling
      pathway," "extracellular matrix receptor interaction," "the phosphatidylinositol
      3 kinase-protein kinase B signaling pathway," and "focal adhesion" signaling
      pathway. RNA-seq results were validated by reverse transcription (RT)-PCR.
      Additionally, Al induced changes to the number and morphology of glial cells in
      the hippocampus of rats, as shown by glial fibrillary acidic protein (GFAP) and
      ionized calcium binding adaptor molecule 1 (Iba1) immunochemistry. RT-PCR and
      western blotting validated the significant increase in expression of glial cell
      related genes GFAP and SOX10 following Al exposure compared with control rats,
      consistent with RNA-seq results. Collectively, these results suggest that
      aberrant mRNAs and lncRNAs respond to Al neurotoxicity, and that glial cell
      related genes play important roles in the Al neurotoxicity mechanism. These
      findings provide the basis for designing targeted approaches for the treatment or
      prevention of Al-induced neurotoxicity.

PMID- 29460114
TI  - Peripheral Administration of Tetanus Toxin Hc Fragment Prevents MPP+ Toxicity In
      Vivo.
AB  - Several studies have shown that intrastriatal application of 1-methyl-4
      phenylpyridinium (MPP+) produces similar biochemical changes in rat to those seen
      in Parkinson's disease (PD), such as dopaminergic terminal degeneration and
      consequent appearance of motor deficits, making the MPP+ lesion a widely used
      model of parkinsonism in rodents. Previous results from our group have shown a
      neuroprotective effect of the carboxyl-terminal domain of the heavy chain of
      tetanus toxin (Hc-TeTx) under different types of stress. In the present study,
      pretreatment with the intraperitoneal injection of Hc-TeTx in rats prevents the
      decrease of tyrosine hydroxylase immunoreactivity in the striatum due to injury
      with MPP+, when applied stereotaxically in the striatum. Similarly, striatal
      catecholamine contents are restored, as well as the levels of two other
      dopaminergic markers, the dopamine transporter (DAT) and the vesicular monoamine
      transporter-2 (VMAT-2). Additionally, uptake studies of [3H]-dopamine and [3H]
      MPP+ reveal that DAT action is not affected by Hc-TeTx, discarding a protective
      effect due to a reduced entry of MPP+ into nerve terminals. Behavioral
      assessments show that Hc-TeTx pretreatment improves the motor skills (amphetamine
      induced rotation, forelimb use, and adjusting steps) of MPP+-treated rats. Our
      results lead us to consider Hc-TeTx as a potential therapeutic tool in
      pathologies caused by impairment of dopaminergic innervation in the striatum, as
      is the case of PD.

PMID- 29460115
TI  - A farewell and a welcome.

PMID- 29460116
TI  - Solid-State Nanopore.
AB  - Solid-state nanopore has captured the attention of many researchers due to its
      characteristic of nanoscale. Now, different fabrication methods have been
      reported, which can be summarized into two broad categories: "top-down" etching
      technology and "bottom-up" shrinkage technology. Ion track etching method, mask
      etching method chemical solution etching method, and high-energy particle etching
      and shrinkage method are exhibited in this report. Besides, we also discussed
      applications of solid-state nanopore fabrication technology in DNA sequencing,
      protein detection, and energy conversion.

PMID- 29460117
TI  - Genomic Characterization of a Novel Hepatovirus from Great Roundleaf Bats in
      China.

PMID- 29460118
TI  - Feasibility of cord blood bank in high altitude Abha: preclinical impacts.
AB  - We explored the possibility of the cryo-storage of cord blood hematopoietic stem
      cells (CBHPSC) with respect to the quantity, quality and biologic efficacy of
      high altitude (HA) region Abha against sea level (SL) region. The results of the
      post-processed total nucleated cell count was 8.03 +/- 0.31 * 107 and 8.44 +/-
      0.23 * 107 cells in the HA and SL regions respectively. The mean post processing
      viability of the nucleated cells was about 87.03 +/- 1.39 (HA) and 88.33 +/-
      1.55% (SL) while post thaw cells were 85.61 +/- 1.44 (HA) and 86.58 +/- 1.61%
      (SL) after transient cryo-storage. The proliferation of CBHSCs after thawing were
      comparable between the HA and SL regions. The results of the colony forming unit
      (CFU) assays of CFU-E, CFU-GEMM, CFU-GM and BFU-E were comparable between HA and
      SL in both fresh and post thaw, while a declining trend with viability was
      significant. The differentiation capability of post thaw samples into adipocytes
      and osteocytes were comparable between HA and SL regions. Overall from the
      results, it can be evidenced that HA cord blood collection, processing or storage
      does not hinder the quality or biological efficacy of the CBHPSC.

PMID- 29460119
TI  - Curcumin Inhibits Monocyte Chemoattractant Protein-1 Expression in TNF-alpha
      induced Astrocytes Through AMPK Pathway.
AB  - Curcumin, a phenolic pigment, plays an inhibitory role in astrocytes activation,
      a key step for neuropathic pain (NP). The present study aimed to investigate the
      mechanism behind the therapeutic effect of Curcumin on NP in vitro. Specifically,
      we investigated the inhibitory effect of Curcumin on tumor necrosis factor-alpha
      (TNF-alpha)-induced astrocyte migration. We also studied the effects of Curcumin
      on monocyte chemoattractant protein-1(MCP-1) expression and activity, as well as
      super oxide dismutase-2 (SOD2) expression and activity in TNF-alpha-induced
      astrocytes. Additionally, we investigated whether the adenosine-monophosphate
      activated protein kinase signaling (AMPK) pathway was involved in this process.
      Our data demonstrated that Curcumin inhibited TNF-alpha-induced astrocytes
      migration, decreased MCP-1 expression, and up-regulated SOD2 expression in TNF
      alpha-induced astrocytes in vitro. Our study also indicated that this process was
      mediated through the AMPK signaling pathway, as addition of Curcumin
      significantly increased the level of phosphorylated AMPK protein. Furthermore,
      the specific AMPK activator AICAR (5-aminoimidazole-4-carboxamide 1-D
      ribofuranoside) mimicked the effects of Curcumin, whereas a selective AMPK
      inhibitor Compound C (also called dorsomorphin) partially blocked its function.
      These results could shed light on understanding of the molecular basis for the
      inhibition of Curcumin on MCP-1 expression during the process of astrocyte
      activation, and provide a molecular mechanism for using Curcumin in neuropathic
      pain.

PMID- 29460120
TI  - New Insights into CO2 Adsorption on Layered Double Hydroxide (LDH)-Based
      Nanomaterials.
AB  - The interlamellar spacing of layered double hydroxides (LDHs) was enlarged by
      dodecyl sulfonate ions firstly, and then, (3-aminopropyl)triethoxysilane (APS)
      was chemically grafted (APS/LDHs). The structural characteristics and thermal
      stability of these prepared samples were characterized by X-ray diffraction
      (XRD), transmission electron microscopy (TEM), reflectance Fourier transform
      infrared spectrometer (FTIR), thermogravimetric analysis (TG), and elemental
      analysis (EA) respectively. The CO2 adsorption performance was investigated
      adopting TG and diffuse reflectance infrared Fourier transform spectroscopy
      (DRIFTS). The results presented that the CO2 adsorption capacity on APS/LDHs was
      as high as 90 mg/g and showed no obvious reduction during a five cyclic
      adsorption-desorption test, indicating its superior performance stability. The
      DRIFTS results showed that both carbamates and weakly bounded CO2 species were
      generated on APS/LDHs. The weakly adsorbed species was due to the different local
      chemical environment for CO2 capture provided by the surface moieties of LDHs
      like free silanol and hydrogen bonds.

PMID- 29460121
TI  - PACAP and its receptors in cranial arteries and mast cells.
AB  - BACKGROUND: In migraineurs pituitary adenylate cyclase activating peptide1-38
      (PACAP1-38) is a potent migraine provoking substance and the accompanying long
      lasting flushing suggests degranulation of mast cells. Infusion of the closely
      related vasoactive intestinal peptide (VIP) either induces headache or flushing.
      This implicates the pituitary adenylate cyclase activating peptide type I
      receptor (PAC1) to be involved in the pathophysiology of PACAP1-38 provoked
      headaches. Here we review studies characterizing the effects of mainly PACAP but
      also of VIP on cerebral and meningeal arteries and mast cells. DISCUSSION: PACAP1
      38, PACAP1-27 and VIP dilate cerebral and meningeal arteries from several species
      including man. In rat cerebral and meningeal arteries the dilation seems to be
      mediated preferably via vasoactive intestinal peptide receptor type 1 (VPAC1)
      receptors while, in human, middle meningeal artery dilation induced via
      vasoactive intestinal peptide receptor type 2 (VPAC2) receptors cannot be ruled
      out. PACAP1-38 is a strong degranulator of peritoneal and dural mast cells while
      PACAP1-27 and VIP only have weak effects. More detailed characterization studies
      suggest that mast cell degranulation is not mediated via the known receptors for
      PACAP1-38 but rather via a still unknown receptor coupled to phospholipase C.
      CONCLUSION: It is suggested that PACAP1-38 might induce migraine via
      degranulation of dural mast cells via a yet unknown receptor.

PMID- 29460122
TI  - Introduction to mammalian genome special issue: the combined role of genetics and
      environment relevant to human disease outcomes.

PMID- 29460124
TI  - Accuracy of cardiac CT in evaluating severity of left atrial appendage
      spontaneous echo contrast: comparison with transesophageal echocardiography.
AB  - To investigate the capacity of biphasic cardiac CT (CCT) for qualitative and
      quantitative evaluation of different grades of left atrial appendage spontaneous
      echo contrast (LAASEC). The study included 267 inpatients with confirmed atrial
      fibrillation who underwent both CCT and transesophageal echocardiography (TEE).
      CT numbers for LAA, ascending aorta (AA), and left atrium (LA) were identified,
      and ROC curves for LAA, LAA/AA, and LAA/LA were plotted. With TEE as the
      standard, the sensitivity, specificity, PPV, NPV, and accuracy of CCT for LAASEC
      grade >= 1 were 60.3, 92.9, 92.4, 64.8, and 75.7%; and for grade >= 2 were 100.0,
      84.4, 71.4, 100.0, and 88.8% respectively. The values of LAA, LAA/AA, and LAA/LA
      were significantly larger in LAASEC grade 0 versus 1 and in grade 1 versus 2, but
      were similar in grades 2 and 3 or in grades 3 and 4. The values of LAA/AA were
      larger in grade 2 versus 4. When the cutoff value for LAA/AA = 0.897,
      sensitivity, specificity, PPV, NPV, and accuracy of CCT for LAASEC grade >= 1 was
      89.6, 83.2, 87.9, 85.5, and 86.9% and with a cutoff for LAA/AA of 0.524, the
      sensitivity, specificity, PPV, NPV, and accuracy for LAASEC grade >= 2 was 98.7,
      92.7, 84.1, 99.4, and 94.4%. Although CCT showed limited diagnostic accuracy for
      grade 1 LAASEC, grade >= 2 LAASEC could be excluded when there was no LAA filling
      defect on first-phase CCT, and TEE can be avoided. CCT has an excellent accuracy
      in diagnosing LAASEC, and quantitative analysis (in particular LAA/AA) is
      superior.

PMID- 29460125
TI  - Bile duct angulation and tumor vascularity are useful radiographic features for
      differentiating pancreatic head cancer and intrapancreatic bile duct cancer.
AB  - BACKGROUND AND PURPOSE: To perform radical resection without leaving residual
      cancer, surgeons must distinguish between pancreatic head cancer (PHC) and
      intrapancreatic bile duct cancer (IPBDC) preoperatively. The aim of this study
      was to establish the points of difference between these two cancers, especially
      on preoperative multi-detector computed tomography (MDCT) images. METHODS: The
      subjects of this study were 28 patients with PHC and proven bile duct invasion
      who underwent pancreatoduodenectomy (PHC group) and 22 patients with IPBDC and
      upstream bile duct dilation (IPBDC group). We compared the preoperative clinical
      and radiographic features, including the bile duct angle, calculated on coronal
      images of MDCT, and the vascularity of the tumor. RESULTS: The optimal cut-off
      values for the bile duct angle, the CT value ratio of the tumor (late arterial
      phase/non-enhanced), and the main pancreatic duct (MPD) ratio (diameter of
      MPD/diameter of parenchyma) were 110 degrees , 3.0, and 0.2, respectively.
      Multivariate analysis revealed that a bile duct angle < 110 degrees , a CT value
      ratio of the tumor < 3, and an MPD ratio >= 0.2 were independently associated
      with PHC. CONCLUSIONS: A bile duct angle and CT value reflecting the vascularity
      of the tumor might be useful radiographic features for differentiating PHC and
      IPBDC, in addition to MPD dilatation.

PMID- 29460126
TI  - Incidence and treatment of metachronous gastric cancer after proximal
      gastrectomy.
AB  - BACKGROUND AND PURPOSE: Proximal gastrectomy (PG) is a widely accepted function
      preserving surgical procedure; however, the incidence and treatment of
      metachronous gastric cancer (MGC) after PG have been the subject of a number of
      reports. METHODS: We collected data from 1576 consecutive patients who underwent
      gastrectomy for gastric cancer between January, 2003 and December, 2010, and
      analyzed the outcomes of 671 patients treated with PG or distal gastrectomy (DG)
      for cT1N0 disease. We also discuss the treatments for MGC. RESULTS: MGC was
      diagnosed within a median follow-up of 52.8 months after PG and DG in six (6.6%)
      and nine (1.8%) patients, respectively. The cumulative prevalence of MGC after PG
      was significantly higher than that after DG; P = 0.005. Univariate and
      multivariate analysis revealed male sex and PG as significant risk factors for
      MGC (P = 0.014 and P = 0.026, respectively). Five of the six patients who
      underwent PG were treated by endoscopic submucosal dissection. CONCLUSIONS: The
      incidence of MGC after PG was significantly higher than that after DG. However,
      most of the MGCs that developed after PG could be treated by endoscopic
      submucosal dissection.

PMID- 29460123
TI  - Warning SINEs: Alu elements, evolution of the human brain, and the spectrum of
      neurological disease.
AB  - Alu elements are a highly successful family of primate-specific retrotransposons
      that have fundamentally shaped primate evolution, including the evolution of our
      own species. Alus play critical roles in the formation of neurological networks
      and the epigenetic regulation of biochemical processes throughout the central
      nervous system (CNS), and thus are hypothesized to have contributed to the origin
      of human cognition. Despite the benefits that Alus provide, deleterious Alu
      activity is associated with a number of neurological and neurodegenerative
      disorders. In particular, neurological networks are potentially vulnerable to the
      epigenetic dysregulation of Alu elements operating across the suite of nuclear
      encoded mitochondrial genes that are critical for both mitochondrial and CNS
      function. Here, we highlight the beneficial neurological aspects of Alu elements
      as well as their potential to cause disease by disrupting key cellular processes
      across the CNS. We identify at least 37 neurological and neurodegenerative
      disorders wherein deleterious Alu activity has been implicated as a contributing
      factor for the manifestation of disease, and for many of these disorders, this
      activity is operating on genes that are essential for proper mitochondrial
      function. We conclude that the epigenetic dysregulation of Alu elements can
      ultimately disrupt mitochondrial homeostasis within the CNS. This mechanism is a
      plausible source for the incipient neuronal stress that is consistently observed
      across a spectrum of sporadic neurological and neurodegenerative disorders.

PMID- 29460127
TI  - Intrathyroid cystic thyroglossal duct remnant and ectopic thymus: a fortuitous or
      development-related association?

PMID- 29460128
TI  - Molecular characterization of Plum pox virus Rec isolates from Russia suggests a
      new insight into evolution of the strain.
AB  - Field isolates of Plum pox virus (PPV), belonging to the strain Rec, have been
      found for the first time in Russia. Full-size genomes of the isolates K28 and
      Kisl-1pl from myrobalan and plum, respectively, were sequenced on the 454
      platform. Analysis of all known PPV-Rec complete genomes using the Recombination
      Detection Program (RDP4) revealed yet another recombination event in the 5'
      terminal region. This event was detected by seven algorithms, implemented in the
      RDP4, with statistically significant P values and supported by a phylogenetic
      analysis with the bootstrap value of 87%. A putative PPV-M-derived segment,
      encompassing the C-terminus of the P1 gene and approximately two-thirds of the
      HcPro gene, is bordered by breakpoints at positions 760-940 and 1838-1964,
      depending on the recombinant isolate. The predicted 5'-distal breakpoint for the
      isolate Valjevka is located at position 2804. The Dideron (strain D) and SK68
      (strain M) isolates were inferred as major and minor parents, respectively.
      Finding of another recombination event suggests more complex evolutionary history
      of PPV-Rec than previously assumed. Perhaps the first recombination event led to
      the formation of a PPV-D variant harboring the PPV-M-derived fragment within the
      5'-proximal part of the genome. Subsequent recombination of its descendant with
      PPV-M in the 3'-proximal genomic region resulted in the emergence of the
      evolutionary successful strain Rec.

PMID- 29460129
TI  - ESR paper on structured reporting in radiology.
AB  - : Structured reporting is emerging as a key element of optimising radiology's
      contribution to patient outcomes and ensuring the value of radiologists' work. It
      is being developed and supported by many national and international radiology
      societies, based on the recognised need to use uniform language and structure to
      accurately describe radiology findings. Standardisation of report structures
      ensures that all relevant areas are addressed. Standardisation of terminology
      prevents ambiguity in reports and facilitates comparability of reports. The use
      of key data elements and quantified parameters in structured reports
      ("radiomics") permits automatic functions (e.g. TNM staging), potential
      integration with other clinical parameters (e.g. laboratory results), data
      sharing (e.g. registries, biobanks) and data mining for research, teaching and
      other purposes. This article outlines the requirements for a successful
      structured reporting strategy (definition of content and structure, standard
      terminologies, tools and protocols). A potential implementation strategy is
      outlined. Moving from conventional prose reports to structured reporting is
      endorsed as a positive development, and must be an international effort, with
      international design and adoption of structured reporting templates that can be
      translated and adapted in local environments as needed. Industry involvement is
      key to success, based on international data standards and guidelines. KEY POINTS:
      * Standardisation of radiology report structure ensures completeness and
      comparability of reports. * Use of standardised language in reports minimises
      ambiguity. * Structured reporting facilitates automatic functions, integration
      with other clinical parameters and data sharing. * International and inter
      society cooperation is key to developing successful structured report templates.
      * Integration with industry providers of radiology-reporting software is also
      crucial.

PMID- 29460130
TI  - Prevalence, Comorbidity, and Correlates of Psychiatric and Substance Use
      Disorders and Associations with HIV Risk Behaviors in a Multisite Cohort of Women
      Living with HIV.
AB  - We used the World Health Organization's Composite International Diagnostic
      Interview to determine the prevalence, comorbidity, and correlates of lifetime
      and 12-month behavioral health disorders in a multisite cohort of 1027 women
      living with HIV in the United States. Most (82.6%) had one or more lifetime
      disorders including 34.2% with mood disorders, 61.6% with anxiety disorders, and
      58.3% with substance use disorders. Over half (53.9%) had at least one 12-month
      disorder, including 22.1% with mood disorders, 45.4% with anxiety disorders, and
      11.1% with substance use disorders. Behavioral health disorder onset preceded HIV
      diagnosis by an average of 19 years. In multivariable models, likelihood of
      disorders was associated with women's race/ethnicity, employment status, and
      income. Women with 12-month behavioral health disorders were significantly more
      likely than their counterparts to engage in subsequent sexual and substance use
      HIV risk behaviors. We discuss the complex physical and behavioral health needs
      of women living with HIV.

PMID- 29460132
TI  - The role of HCN channels in peristaltic dysfunction in human ureteral
      tuberculosis.
AB  - OBJECTIVE: To explore the role of HCN channels in ureteral peristaltic
      dysfunction by comparing the changes in HCN channel levels between normal and
      tuberculous ureters. METHODS: A total of 32 specimens of human upper ureters were
      collected by nephrectomy from patients with renal tumor (control group, n = 16)
      or from patients with renal tuberculosis (experimental group, n = 16); the two
      groups did not receive radiotherapy, chemotherapy, immunotherapy, or any other
      special treatment before the surgical procedure. An experimental study on smooth
      muscle strips of human upper ureters showed variation in contraction amplitude
      and frequency after adding ZD7288, a specific blocker of HCN channels. The
      expression of HCN channels in the ureter was confirmed by Western blot (WB) and
      by confocal analysis of double immunostaining for c-kit and HCN channel proteins.
      RESULTS: Before the addition of ZD7288, the experimental and control groups
      showed significant differences in the frequency and amplitude of the spontaneous
      contraction of isolated ureteral smooth muscle strips. After ZD7288 was added,
      the frequency and amplitude of the contractions of the ureteral smooth muscle
      strips were significantly lower in both groups. The differences observed before
      and after ZD7288 treatment in each group were significant (P < 0.001), and the
      difference in contraction amplitude observed between the two groups before ZD7288
      was also significantly different (P < 0.001). By using WB technology, we showed
      that the expression of HCN channels was present in normal human ureters, with the
      expression of HCN4 and HCN1 being the highest; the expression of HCN4 and HCN1 in
      the control and experimental groups were both statistically significant (P <
      0.001). HCN4 and HCN1 were expressed in the mucosal and smooth muscle layers of
      human control ureters and tuberculous ureters, as revealed by a confocal analysis
      of double immunostaining for c-kit and HCNs proteins; there were significant
      differences between the two groups (P < 0.001). CONCLUSION: Four HCN channels are
      expressed in the ureter, mainly HCN4 and HCN1, suggesting that HCN channels are
      involved in the peristaltic contraction of ureteral ICCs, which may be an
      important reason for peristaltic dysfunction in ureteric tuberculosis.

PMID- 29460131
TI  - Inhibiting autophagy overcomes docetaxel resistance in castration-resistant
      prostate cancer cells.
AB  - BACKGROUND: This study investigates the docetaxel-resistant mechanism and
      explores the effect of tea polyphenols (TP) on autophagy and its related
      mechanism in human castration-resistant prostate cancer (CRPC) cell lines PC3 and
      DU145. METHODS: Immunofluorescence assay and annexin V-FITC/PI double staining
      flow cytometry were used to analyze the apoptosis and autophagy of PC3 and DU145
      cells. The expression of autophagy-related proteins was detected by western bolt.
      RESULTS: Docetaxel could induce autophagy and apoptosis, together with the
      expression increase in p-JNK, p-Bcl-2 and Beclin1. The level of autophagy was
      remarkably decreased, but apoptosis was increased after combining with TP. In
      addition, the expression of p-mTOR was increased after combining with TP.
      CONCLUSION: Docetaxel induces protective autophagy in CRPC cells by JNK pathway
      activation and then Bcl-2 phosphorylation and Beclin1 dissociation. TP activates
      mTOR pathway, which ultimately inhibits docetaxel-induced autophagy and improves
      therapeutic efficacy of docetaxel in CRPC cells.

PMID- 29460133
TI  - Effects of metformin on prostatic tissue of rats with metabolic syndrome and
      benign prostatic hyperplasia.
AB  - OBJECTIVES: To investigate the efficacy of insulin sensitizer on prostatic tissue
      in animal model with benign prostatic hyperplasia (BPH) secondary to metabolic
      syndrome (MetS). METHODS: Models were established by providing Sprague-Dawley
      rats with high fat diet (HFD) combined with metformin or not. All objects were
      killed 40 days later with prostatic tissue being removed, weighed before stained,
      as well as the expression level of insulin-like growth factor I (IGF-1) and
      receptor (IGF-1R) being measured, and the level of insulin resistance (IR) has
      also been evaluated. RESULTS: Model has been successfully established. Level of
      prostatic hyperplasia and IR as well as IGF-1 and IGF-1R expressions in the blank
      and saline control subunits of HFD group was higher than that of normal diet
      group (P < 0.05). In the subunit of metformin, along with the suppression of IR,
      the level of prostatic hyperplasia and the expression of IGF-1 pathway have both
      decreased (P < 0.05). CONCLUSION: MetS can promote the growth of prostate during
      the formation of central obesity and IR. IGF-1 pathway may have an important role
      in the induction of BPH following IR. The application of metformin can suppress
      the expression of IGF-1 and IGF-1R, thus preventing the promotive effect of IR on
      prostate tissue in animal model of MetS.

PMID- 29460134
TI  - Perceived Racial Discrimination and Pain Intensity/Disability Among Economically
      Disadvantaged Latinos in a Federally Qualified Health Center: The Role of Anxiety
      Sensitivity.
AB  - The present study examined the role of anxiety sensitivity (AS; fear of the
      negative consequences of anxiety) in the relation between perceived racial
      discrimination and pain-related problems among Latinos seeking health services at
      a Federally Qualified Health Center. Participants included 145 adult Latinos
      (87.80% female, Mage = 38.07 years, SD = 11.98, and 96.2% reported Spanish as
      their first language). Results indicated that perceived racial discrimination was
      indirectly related to the pain intensity and pain disability through AS. These
      effects were evident above and beyond the variance accounted for by gender, age,
      marital status, educational status, employment status, years living in the United
      States, and number of axis I diagnoses. Overall, the present findings highlight
      the merit in focusing further scientific attention on the interplay between
      perceived racial discrimination and AS to better understand and inform
      interventions to reduce pain problems among Latinos in primary care.

PMID- 29460135
TI  - Simvastatin reduces adrenal catecholamine secretion evoked by stimulation of
      cholinergic nicotinic and angiotensinergic AT1 receptors.
AB  - We investigated the influence of simvastatin, a statin, on the secretion of
      catecholamines (CA) in rat adrenal glands, and clarified its action mechanism.
      Simvastatin suppressed acetylcholine (ACh)-evoked CA release in a dose- and time
      dependent fashion. In the presence of simvastatin, CA secretion evoked by 1.1
      dimethyl-4-phenyl piperazinium iodide (DMPP), angiotensin II, high K+,
      veratridine, and Bay-K-8644 was time-dependently inhibited. However, in the
      simultaneous presence of simvastatin and Nomega-nitro-L-arginine methyl ester
      hydrochloride, CA secretion evoked by angiotensin II and DMPP recovered to
      control levels. Adrenal NO release was increased by simvastatin-treatment.
      Simvastatin-inhibited CA secretion was not affected by treatment with mevalonate.
      Pravastatin did not influence ACh-evoked CA secretion, while atorvastatin reduced
      it. In the simultaneous presence of simvastatin and fimasartan, ACh-induced CA
      release was markedly reduced compared to that of fimasartan-treatment alone. We
      present the first evidence that simvastatin reduces adrenal CA secretion induced
      by stimulation of nicotinic and AT1-receptors. Simvastatin-induced inhibition
      seems to involve reducing the influx of both Ca2+ and Na+ into adrenochromaffin
      cells, partly via the elevation of NO production by NO synthase activation,
      without inhibition of 3-hydroxy-methylglutaryl coenzyme A reductase. Co
      administration of simvastatin and fimasartan may be clinically helpful for the
      treatment of cardiovascular diseases.

PMID- 29460136
TI  - Development and Assessment of a Helicobacter pylori Medication Adherence and
      Stomach Cancer Prevention Curriculum for a Chinese American Immigrant Population.
AB  - Chinese American immigrants are at increased risk for Helicobacter pylori
      infection and stomach cancer. Despite their increased risk, very few prevention
      strategies exist which target this vulnerable population. The purpose of this
      article is to present the stakeholder engaged development, review, assessment,
      refinement, and finalization of a H. pylori treatment adherence and stomach
      cancer prevention curriculum specifically designed to engage vulnerable, limited
      English proficient Chinese Americans in New York City.

PMID- 29460137
TI  - On Writing.

PMID- 29460138
TI  - Brush sign in Sturge-Weber syndrome.

PMID- 29460139
TI  - Thanks from Iraq.

PMID- 29460140
TI  - Sarcocystis cymruensis: discovery in Western Hemisphere in the Brown rat (Rattus
      norvegicus) from Grenada, West Indies: redescription, molecular characterization,
      and transmission to IFN-gamma gene knockout mice via sporocysts from
      experimentally infected domestic cat (Felis catus).
AB  - Rodents are intermediate hosts for many species of Sarcocystis. Little is known
      of Sarcocystis cymruensis that uses the Brown rat (Rattus norvegicus) as
      intermediate hosts and the domestic cat (Felis catus) as experimental definitive
      host. Here, we identified and described Sarcocystis cymruensis in naturally
      infected R. norvegicus from Grenada, West Indies. Rats (n = 167) were trapped in
      various locations in two parishes (St. George and St. David). Microscopic, thin
      (< 1 MUm) walled, slender sarcocysts were found in 11 of 156 (7.0%) rats skeletal
      muscles by squash examination. A laboratory-raised cat fed naturally infected rat
      tissues excreted sporocysts that were infectious for interferon gamma gene
      knockout (KO) mice, but not to Swiss Webster outbred albino mice. All inoculated
      mice remained asymptomatic, and microscopic S. cymruensis-like sarcocysts were
      found in the muscles of KO mice euthanized on day 70, 116, and 189 post
      inoculation (p.i.). Sarcocysts from infected KO mice were infective for cats at
      day 116 but not at 70 days p.i. By transmission electron microscopy, the
      sarcocyst wall was "type 1a." Detailed morphological description of the cyst
      wall, metrocytes, and bradyzoites is given for the first time. Additionally,
      molecular data on S. cymruensis are presented also for the first time. Molecular
      characterization of sarcocysts 18S rDNA and 28S rDNA, ITS-1, and cox1 loci showed
      the highest similarity with S. rodentifelis and S. muris. In conclusion, the
      present study described the natural infection of S. cymruensis in Brown rat for
      the first time in a Caribbean country and provided its molecular characteristics.

PMID- 29460141
TI  - Complete Restitution of the Ischemic Penumbra after Successful Thrombectomy : A
      Pilot Study Using Quantitative MRI.
AB  - PURPOSE: Endovascular thrombectomy is highly effective in patients with proximal
      large artery occlusion but the relevance of reperfusion injury after
      recanalization is a matter of debate. The aim of this study was to investigate
      potential residual metabolic distress and microstructural tissue damage or edema
      after reperfusion using quantitative oxygen-sensitive T2' and T2-mapping in
      patients successfully treated by thrombectomy. METHODS: Included in this study
      were 11 patients (mean age 70 +/- 11.4 years) with acute ischemic stroke due to
      internal carotid artery and/or middle cerebral artery occlusion. Quantitative T2
      and T2' (1/T2' = 1/T2* - 1/T2) were determined within the ischemic core and
      hypoperfused but salvaged tissue with delayed time-to-peak (TTP) in patients
      before and after successful thrombectomy and compared to a control region within
      the unaffected hemisphere. RESULTS: Decreased T2' values within hypoperfused
      tissue before thrombectomy showed a normalization after recanalization (p <
      0.01). In formerly hypoperfused but salvaged tissue, T2 values increased
      significantly after thrombectomy (p < 0.05) but did not differ from reference
      values in the control region. In salvaged tissue, increases of quantitative T2'
      and T2 to follow-up were more pronounced in areas with severe TTP delay.
      CONCLUSION: After successful recanalization, T2' re-increased back to normal in
      formerly hypoperfused areas as a sign of prompt normalization of oxygen
      metabolism. Furthermore, quantitative T2 in the formerly hypoperfused tissue did
      not differ from reference values in unaffected tissue. These results indicate
      complete restitution of salvaged tissue after reperfusion and support the overall
      safety of endovascular thrombectomy with respect to microstructural tissue
      integrity.

PMID- 29460142
TI  - Investigation of Neurodegenerative Processes in Amyotrophic Lateral Sclerosis
      Using White Matter Fiber Density.
AB  - In the current work two novel parameters, fiber density (FD) and mean diffusion
      signal (MDS) are investigated for evaluating neurodegenerative processes in
      amyotrophic lateral sclerosis (ALS). The MDS provides a measure of the FD but is
      derived directly from the diffusion signal. Using tract-based spatial statistics
      (TBSS), pathological changes across the entire white matter and changes in the
      parameters over time were evaluated. The results were related to those obtained
      using the fractional anisotropy (FA) value. A widespread pattern of significantly
      decreased FD and MDS values was observed. A strong trend towards statistical
      significance was seen in similar white matter structures using TBSS analysis
      based on the FA value. Longitudinal analysis of the FD values demonstrated
      continuing deterioration of the same fiber tracts that were shown to be impaired
      in the group analysis. The findings suggest that MDS and in particular FD show
      great promise for evaluating microstructural white matter changes in ALS and may
      be more sensitive than the more commonly used FA value.

PMID- 29460143
TI  - Listening in the bog: II. Neural correlates for acoustic interactions and spacing
      between Sphagniana sphagnorum males.
AB  - Males of the katydid Sphagniana sphagnorum maintain inter-male distances from one
      another using agonistic song interactions with a frequency-modulated song that
      consists of alternating audio and ultrasonic parts. We studied the neuronal
      representation of this song in auditory receptors and interneurons of receivers,
      using playbacks of songs that mimicked the absolute and relative sound pressure
      levels of the two song modes varying with distance. The tuning and sensitivity of
      both receptors and interneurons strongly determine their responses to the two
      song modes at different distances. Low-frequency interneurons respond
      preferentially to the audio mode of the song at larger distances. High-frequency
      (HF) interneurons respond preferentially to the HF component of the song at close
      range. 'Switch interneurons' are sensitive to both spectral song components, but
      exhibit a typical activity switch towards the high-frequency mode at distances
      nearer than 3-6 m. The activity of the latter two groups of interneurons
      correlates with the distance in the field at which males begin to interact
      acoustically with their neighbours. Important information about the rate of
      changes in the song mode is represented by the afferent activity despite the
      influence of the masking song produced by a sympatric katydid species.

PMID- 29460144
TI  - Negative errors in time reproduction tasks.
AB  - In time reproduction tasks, the reaction time of motor responses is intrinsically
      linked to the measure of perceptual timing. Decisions are based on a continuous
      comparison between elapsed time and a memory trace of the to-be-reproduced
      interval. Here, we investigate the possibility that negative reproduction errors
      can be explained by the tendency to prefer earlier over later response times, or
      whether the whole range of possible response times is shifted. In experiment 1,
      we directly compared point reproduction (participants indicate the exact time
      point of equality) and range reproduction (participants bracket an interval
      containing this time point). In experiment 2, participants indicated, in three
      separate tasks, the exact time point at which the reproduction phase was equal to
      the standard duration (point reproduction), the earliest (start reproduction), or
      the latest moment (stop reproduction) at which the exact time point of equality
      might have been reached. The results demonstrate that the bias towards earlier
      responses not only affects reproduction of the exact time point of equality.
      Rather, even if the decision threshold is changed in favor of late responses,
      they exhibit a continuous shift towards negative errors that increases with the
      length of the standard duration. The findings are discussed in the context of the
      hypothesis that systematic errors in time reproduction tasks reflect a dimension
      unspecific tendency towards earlier responses caused by the psychophysical method
      rather than by a time-specific perceptual distortion.

PMID- 29460145
TI  - A Paper-Based Analytical Device Based on Combination of Thin Film Microextraction
      and Reflection Scanometry for Sensitive Colorimetric Determination of Ni(II) in
      Aqueous Matrix.
AB  - In this research, the thin film microextraction method was applied for the
      extraction of Ni(II) ion from aqueous matrixes. Chemically modified cellulosic
      filter paper with phosphorus was used as a thin film extractor. After extraction,
      the thin film was treated with a solution of dimethylglyoxime. The colored film
      was captured by flatbed scanner and the absorbance of the images was extracted by
      some suitable software. Under the optimum conditions and at the pH 7.0, with the
      sample volume of 100 mL, the stirring rate of 800 rpm, and the extraction time of
      50 min, the calibration curve was obtained in the range of 0.05-5 mg/L Ni(II) (R2
      = 0.989). Limit and relative standard deviation were achieved to be 18 ug/L and
      less than 6.7%, respectively. Relative recoveries were obtained in the range of
      87%-105%. Finally, the proposed method was found to be simple and cost-effective,
      with adequate analytical performance for the rapid detection of Ni(II) in river
      and wastewater samples.

PMID- 29460146
TI  - Sex-specific thermal sensitivities of performance and activity in the asian house
      gecko, Hemidactylus frenatus.
AB  - Studies of sexual selection primarily focus on morphological traits such as body
      size and secondary trait dimorphism, with less attention been given to the
      functional differences between the sexes and even more so their thermal
      performance capacities. Each sex may benefit from possessing different thermal
      performance capacities that would allow them to maximise their fitness relative
      to their different reproductive roles; especially when performances are closely
      related to reproductive success. Here, we examine sexual divergence in thermal
      sensitivities of performance across three populations of the Asian house gecko
      (Hemidactylus frenatus) over an extensive latitudinal cline. Using analyses of
      the thermal sensitivity of routine activity, bite force and sprint speed, we
      explored whether: (i) males and females differed in their optimal temperatures
      for performance, (ii) the sexes differed in their thermal sensitivities of
      performance, and (iii) the degree of sexual divergence in thermal sensitivity
      varied among the populations. Because male H. frenatus are highly aggressive and
      frequently engage in combat to gain territories and mating opportunities, we
      expected males would be active over a wider range of temperatures than females
      and this would favour broad thermal sensitivity curves for males. In addition, we
      expected a greater divergence between the sexes in thermal sensitivities for the
      temperate populations that experience greater daily and seasonal thermal
      variation. We found that males were more active, and had greater bite forces and
      faster sprint speeds than females, independent of body size. In addition, we
      found differences between the sexes in thermal sensitivities for the tropical
      population; female H. frenatus were less active and possessed lower sprint speeds
      at higher temperatures than males. Although H. frenatus from the most variable
      thermal environments also displayed the broadest thermal performance range, it
      was the more stable tropical population that exhibited the greatest divergence
      between the sexes in thermal sensitivity of performance. The divergence in
      thermal physiology that we detected between the sexes of H. frenatus is
      consistent with the idea that males will derive mating and territorial advantages
      for maintaining function over a broader range of temperatures.

PMID- 29460148
TI  - Impact of vitamin D deficiency on clinical parameters in treatment-naive
      rheumatoid arthritis patients.
AB  - OBJECTIVE: To determine if patients with rheumatoid arthritis (RA) are at risk of
      vitamin D deficiency and whether the levels of vitamin D are correlated with
      clinical parameters in RA. METHODS: A total of 280 treatment-naive RA patients,
      and 140 age- and sex-matched healthy volunteers were enrolled. Serum levels of
      1,25-dihydroxycholecalciferol (1,25(OH)2D3), the active form of vitamin D, were
      measured by enzyme-linked immunosorbent assay (ELISA). Concentrations of
      1,25(OH)2D3 less than 25 ng/mL were defined as insufficient. Linear regression
      was performed to evaluate correlations as (modifying and) confounding factors
      were controlled. RESULTS: The levels of serum 1,25(OH)2D3 in RA individuals
      (12.24 +/- 6.68 ng/ml) were significantly lower than in healthy controls (21.08
      +/- 7.14 ng/ml; p < 0.05). An inverse association was found between the levels of
      1,25(OH)2D3 and ESR in obese and overweight individuals with RA (betaobese = 
      0.385, betaoverweight = -0.395, both p < 0.05), but not in normal and underweight
      subjects. A significant negative association between levels of 1,25(OH)2D3 and
      DAS28 score (beta = -0.164, p = 0.018) was observed. The levels of 1,25(OH)2D3
      were associated moderately and inversely with the absolute numbers of Th-17 (beta
      = -0.158, p = 0.019) and positively with those of CD4+ regulatory T (Treg) cell
      (beta = 0.146, p = 0.025). The levels of 1,25(OH)2D3 in anti-cyclic citrullinated
      peptide (anti-CCP)-positive patients with RA were lower than in the anti-CCP
      negative RA patients (10.86 ng/ml versus 15.98 ng/ml; t = -3.08, p < 0.01).
      CONCLUSIONS: A significant association was observed between levels of vitamin D
      and parameters of disease, including body mass index (BMI), DAS28, Th17 cell
      counts, Treg cell counts, and presence of anti-CCP antibody in RA patients.

PMID- 29460147
TI  - Self-reported history of stroke and long-term living conditions near air
      pollution sources: results of a national epidemiological study in Lebanon.
AB  - Stroke is a disease related to high mortality and morbidity, particularly in
      developing countries. Some studies have linked self-reported indoor and outdoor
      pollution to stroke and mini-stroke, while some others showed no association. Our
      objective was to assess this association in Lebanon, a Middle Eastern developing
      country. A national cross-sectional study was conducted all over Lebanon. In
      addition to self-reported items of pollution exposure, we assessed potential
      predictors of stroke and mini-stroke, including sociodemographic characteristics,
      self-reported health information, and biological measurements. Moreover, we
      assessed dose-effect relationship of pollution items in relation with stroke.
      Self-reported indoor pollution exposure was associated with stroke and mini
      stroke, with or without taking biological values into account. Moreover, we found
      a dose-effect relationship of exposure with risk of disease, but this effect did
      not reach statistical significance after adjustment for sociodemographics and
      biological characteristics. No association was found for any outdoor pollution
      item. Although additional studies would be necessary to confirm these findings,
      sensitizing the population about the effect of pollution on chronic diseases,
      working on reducing pollution, and improving air quality should be implemented to
      decrease the burden of the disease on the population and health system.

PMID- 29460149
TI  - Inferring causal relationships between phenotypes using summary statistics from
      genome-wide association studies.
AB  - Genome-wide association studies (GWAS) have successfully identified numerous
      genetic variants associated with diverse complex phenotypes and diseases, and
      provided tremendous opportunities for further analyses using summary association
      statistics. Recently, Pickrell et al. developed a robust method for causal
      inference using independent putative causal SNPs. However, this method may fail
      to infer the causal relationship between two phenotypes when only a limited
      number of independent putative causal SNPs identified. Here, we extended
      Pickrell's method to make it more applicable for the general situations. We
      extended the causal inference method by replacing the putative causal SNPs with
      the lead SNPs (the set of the most significant SNPs in each independent locus)
      and tested the performance of our extended method using both simulation and
      empirical data. Simulations suggested that when the same number of genetic
      variants is used, our extended method had similar distribution of test statistic
      under the null model as well as comparable power under the causal model compared
      with the original method by Pickrell et al. But in practice, our extended method
      would generally be more powerful because the number of independent lead SNPs was
      often larger than the number of independent putative causal SNPs. And including
      more SNPs, on the other hand, would not cause more false positives. By applying
      our extended method to summary statistics from GWAS for blood metabolites and
      femoral neck bone mineral density (FN-BMD), we successfully identified ten blood
      metabolites that may causally influence FN-BMD. We extended a causal inference
      method for inferring putative causal relationship between two phenotypes using
      summary statistics from GWAS, and identified a number of potential causal
      metabolites for FN-BMD, which may provide novel insights into the
      pathophysiological mechanisms underlying osteoporosis.

PMID- 29460150
TI  - pH Modulation of Voltage-Gated Sodium Channels.
AB  - Changes in blood and tissue pH accompany physiological and pathophysiological
      conditions including exercise, cardiac ischemia, ischemic stroke, and cocaine
      ingestion. These conditions are known to trigger the symptoms of electrical
      diseases in patients carrying sodium channel mutations. Protons cause a diverse
      set of changes to sodium channel gating, which generally lead to decreases in the
      amplitude of the transient sodium current and increases in the fraction of non
      inactivating channels that pass persistent currents. These effects are shared
      with disease-causing mutants in neuronal, skeletal muscle, and cardiac tissue and
      may be compounded in mutants that impart greater proton sensitivity to sodium
      channels, suggesting a role of protons in triggering acute symptoms of electrical
      disease.In this chapter, we review the mechanisms of proton block of the sodium
      channel pore and a suggested mode of action by which protons alter channel
      gating. We discuss the available data on isoform specificity of proton effects
      and tissue level effects. Finally, we review the role that protons play in
      disease and our own recent studies on proton-sensitizing mutants in cardiac and
      skeletal muscle sodium channels.

PMID- 29460151
TI  - Sphingosine Kinases as Druggable Targets.
AB  - There is substantial evidence that the enzymes, sphingosine kinase 1 and 2, which
      catalyse the formation of the bioactive lipid sphingosine 1-phosphate, are
      involved in pathophysiological processes. In this chapter, we appraise the
      evidence that both enzymes are druggable and describe how isoform-specific
      inhibitors can be developed based on the plasticity of the sphingosine-binding
      site. This is contextualised with the effect of sphingosine kinase inhibitors in
      cancer, pulmonary hypertension, neurodegeneration, inflammation and sickling.

PMID- 29460152
TI  - Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator and Drugs:
      Insights from Cellular Trafficking.
AB  - The eukaryotic cell is organized into membrane-delineated compartments that are
      characterized by specific cadres of proteins sustaining biochemically distinct
      cellular processes. The appropriate subcellular localization of proteins is key
      to proper organelle function and provides a physiological context for cellular
      processes. Disruption of normal trafficking pathways for proteins is seen in
      several genetic diseases, where a protein's absence for a specific subcellular
      compartment leads to organelle disruption, and in the context of an individual, a
      disruption of normal physiology. Importantly, several drug therapies can also
      alter protein trafficking, causing unwanted side effects. Thus, a deeper
      understanding of trafficking pathways needs to be appreciated as novel
      therapeutic modalities are proposed. Despite the promising efficacy of novel
      therapeutic agents, the intracellular bioavailability of these compounds has
      proved to be a potential barrier, leading to failures in treatments for various
      diseases and disorders. While endocytosis of drug moieties provides an efficient
      means of getting material into cells, the subsequent release and endosomal escape
      of materials into the cytosol where they need to act has been a barrier. An
      understanding of cellular protein/lipid trafficking pathways has opened up
      strategies for increasing drug bioavailability. Approaches to enhance endosomal
      exit have greatly increased the cytosolic bioavailability of drugs and will
      provide a means of investigating previous drugs that may have been shelved due to
      their low cytosolic concentration.

PMID- 29460153
TI  - GABA and Glutamate Synaptic Coadaptations to Chronic Ethanol in the Striatum.
AB  - Alcohol (ethanol) is a widely used and abused drug with approximately 90% of
      adults over the age of 18 consuming alcohol at some point in their lifetime.
      Alcohol exerts its actions through multiple neurotransmitter systems within the
      brain, most notably the GABAergic and glutamatergic systems. Alcohol's actions on
      GABAergic and glutamatergic neurotransmission have been suggested to underlie the
      acute behavioral effects of ethanol. The striatum is the primary input nucleus of
      the basal ganglia that plays a role in motor and reward systems. The effect of
      ethanol on GABAergic and glutamatergic neurotransmission within striatal
      circuitry has been thought to underlie ethanol taking, seeking, withdrawal and
      relapse. This chapter reviews the effects of ethanol on GABAergic and
      glutamatergic transmission, highlighting the dynamic changes in striatal
      circuitry from acute to chronic exposure and withdrawal.

PMID- 29460154
TI  - Comparison of single versus two non-compression miniplates in the management of
      unfavourable angle fracture of the mandible: a prospective randomized clinical
      study.
AB  - PURPOSE: The purpose of this study was to compare the efficacy of single versus
      two non-compression miniplates in the management of unfavourable angle fracture
      of mandible. MATERIALS AND METHODS: A total of 28 patients who required open
      reduction of mandibular angle fracture were included in the study. The patients
      were randomly divided into two groups. Group I comprised of patients treated with
      two miniplates and those in group II were treated with single non-compression
      miniplate. The parameters of assessment were malocclusion, surgical site
      infection, need for implant removal, duration of surgery, inter-incisal mouth
      opening and cost of implants used, in both the groups. Statistical analysis was
      carried out to compare all the parameters. RESULTS: Out of 14 patients in group
      II, inadequate reduction was noticed in three patients, whereas screw loosening
      had occurred in two cases. Screw loosening was always associated with chronic
      infection. In these cases, hardware removal was deemed necessary. Plate bending
      was observed in two cases resulting in malocclusion and difficulty in eating. Non
      union of fracture occurred in one patient treated in group II. In group I, no
      plate bending, screw loosening, surgical site infection, non-union or
      malocclusion was observed. No patient had to undergo implant removal in group I.
      CONCLUSION: In the management of unfavourable mandibular angle fracture, two
      miniplates must be preferred over the use of single miniplate as using two
      miniplates results in better results with minimal complications.

PMID- 29460155
TI  - Pelvic reconstructions following peri-acetabular bone tumour resections using a
      cementless ice-cream cone prosthesis with dual mobility cup.
AB  - PURPOSE: Despite numerous reconstructive techniques and prosthetic devices,
      pelvic reconstructions following peri-acetabular malignant tumours resections are
      highly challenging. In the present study, we describe our experience with the
      Integra(r) (Lepine, Genay, France) ice-cream cone prosthesis in such indications.
      The objective was to assess the mid-term outcomes of this device. METHODS: Twenty
      four patients' chart with peri-acetabular malignant tumours, who underwent types
      II or II + III peri-acetabular resections according to Enneking and Dunham with
      subsequent reconstruction using the Integra(r) prosthesis between February 2009
      and February 2015, were reviewed. Seventeen cases were primary surgeries and
      seven cases were revisions (i.e., failures of previous reconstructions for pelvic
      tumours). All living patients with the prosthesis implanted were functionally
      assessed, using the musculoskeletal tumour society (MSTS) and Postel-Merle
      d'Aubigne (PMA) scores. RESULTS: After a mean follow-up of 49 +/- 26 months
      (range, 8 to 94 months), 21 patients were alive (88%), including 15 patients
      continuously disease-free (63%). MSTS and PMA scores averaged 72 +/- 13% (range,
      43 to 87%) and 14.6 +/- 2.6 (range, 9 to 18), respectively. Fourteen patients
      (58%) presented at least one complication during follow-up, including four cases
      of deep infection (17%), four cases of dislocation (17%), and two mechanical
      failures (8%). At 5 years, the implant survival rate was 75%. CONCLUSIONS: In
      comparison to previous reconstructive techniques that we used in similar
      indications, functional and oncologic outcomes were improved with the Integra(r)
      implant. However, as commonly observed in pelvic bone tumour surgery,
      complication rates remain significant. LEVEL OF EVIDENCE: Therapeutic, Level IV
      Retrospective Cases Series.

PMID- 29460156
TI  - Comments on article by Tsvieli et al.: manipulation under anaesthetic for frozen
      shoulder using Codman's paradox: a safe and early return of function.

PMID- 29460157
TI  - Uncommon cribfellows: an infant with hypercalcemia, nephrocalcinosis, and
      acidosis: Questions.

PMID- 29460158
TI  - Uncommon cribfellows: an infant with hypercalcemia, nephrocalcinosis, and
      acidosis: Answers.

PMID- 29460160
TI  - Unethical human research in the field of neuroscience: a historical review.
AB  - Understanding the historical foundations of ethics in human research are key to
      illuminating future human research and clinical trials. This paper gives an
      overview of the most remarkable unethical human research and how past misconducts
      helped develop ethical guidelines on human experimentation such as The Nuremberg
      Code 1947 following WWII. Unethical research in the field of neuroscience also
      proved to be incredibly distressing. Participants were often left with life-long
      cognitive disabilities. This emphasizes the importance of implicating strict
      rules and ethical guidelines in neuroscience research that protect participants
      and respects their dignity. The experiments conducted by German Nazi in the
      concentration camps during WWII are probably the most inhumane and brutal ever
      conducted. The Nuremberg Code of 1947, one of the few positive outcomes of the
      Nazi experiments, is often considered the first document to set out ethical
      regulations of human research. It consists of numerous necessary criteria, to
      highlight a few, the subject must give informed consent, there must be a concrete
      scientific basis for the experiment, and the experiment should yield positive
      results that cannot be obtained in any other way. In the end, we must remember,
      the interest of the patient must always prevail over the interest of science or
      society.

PMID- 29460159
TI  - Management of Esophageal Food Impaction Varies Among Gastroenterologists and
      Affects Identification of Eosinophilic Esophagitis.
AB  - BACKGROUND AND AIMS: Esophageal food impaction (EFI) is a gastrointestinal
      emergency requiring immediate evaluation in the emergency room (ER) and an
      esophagogastroduodenoscopy (EGD) for disimpaction. EFI is also a distinct
      presenting feature of eosinophilic esophagitis (EoE). This study aimed at
      understanding the management of EFI among gastroenterologists (GIs) and estimated
      its impact on identification of EoE in USA. METHODS: GIs associated with three
      major gastroenterology societies based in USA were invited to participate in a
      web-based survey. Information on the resources available and utilized, and the
      clinical decision-making process related to management of EFI cases was collected
      and analyzed. RESULTS: Of 428 responses, 49% were from pediatric GIs, 86%
      practiced in the USA, and 78% practiced in an academic setting. Compared to the
      pediatric GIs, adult GIs were more likely to perform EGD in the emergency room
      [OR 87.96 (25.43-304.16)] and advance the food bolus into stomach [5.58 (3.08
      10.12)]. Only 34% of respondents obtained esophageal biopsies during EGD, and
      pediatric GIs were more likely to obtain esophageal biopsies [3.49 (1.12-10.84)]
      compared to adult GIs. In USA, by our conservative estimates, 10,494 patients
      presenting to ER with EFI and at risk of EoE are likely being missed each year.
      CONCLUSIONS: EFI management varies substantially among GIs associated with three
      major gastroenterology societies in USA. Based on their practice patterns, the
      GIs in USA are likely to miss numerous EoE patients presenting to ER with EFI.
      Our findings highlight the need for developing and disseminating evidence-based
      EFI management practice guidelines.

PMID- 29460161
TI  - Saliva changes in Parkinson's disease patients after injection of Botulinum
      neurotoxin type A.
AB  - Patients with Parkinson's disease (PD) are compromised by poor oral condition due
      to oropharyngeal bradykinesia, dysphagia, and the side effects of treatment.
      Intrasalivary gland injections of Botulinum neurotoxin type A (BNT-A) have been
      known to treat sialorrhea effectively in these patients. However, the decreased
      amount of saliva reduces self-cleaning ability that deteriorates oral hygiene and
      increases dental caries. The aim of this study was to determine the changes in
      the oral microflora and saliva in patients with PD treated for sialorrhea by
      means of sonography-controlled BNT-A injections into the bilateral parotid and
      submandibular glands. Altogether, 38 persons participated in the study: 12 PD
      patients who were injected with BNT-A for treatment of sialorrhea and passed
      salivary tests before and 1 month after the injections; and 13 PD patients and 13
      healthy subjects who were not injected with BNT-A and passed salivary tests once.
      The condition of oral health was measured by the amount of saliva, salivary flow
      rate, and salivary composition. A good outcome with a significant decrease in
      salivary flow rate occurred at 1-month follow-up in the BNT-A-treated group while
      no significant change was found in salivary composition. BNT-A treatment did not
      change the Streptococcus mutans levels in saliva but there was statistically
      significant increase in levels of Lactobacilli. BNT-A injections can effectively
      treat sialorrhea while considering the change of oral microflora, and the
      patients should be under dentists' care more frequently. EudraCT clinical trial
      number: 2015-000682-30.

PMID- 29460162
TI  - Furthering Our Understanding of Therapist Knowledge and Attitudinal Measurement
      in Youth Community Mental Health.
AB  - Examining therapist evidence-based practice (EBP) knowledge seems an important
      step for supporting successful implementation. Advances in implementation science
      suggest a distinction between practice specific (i.e., knowing which practices
      are derived from the evidence base) and EBP process (i.e., integrating research
      evidence, clinical experience, client characteristics, and monitoring outcomes)
      knowledge. An examination of how these knowledge types are measured and relate to
      attitudes appears warranted. In our sample of 58 youth community therapists, both
      practice specific and EBP process knowledge accounted for EBP attitude scores,
      which varied by therapist demographic variables. Implications for measurement of
      therapist constructs and future research in identifying therapist predictors of
      EBP use and youth clinical improvement are discussed.

PMID- 29460163
TI  - Noradrenergic targets for the treatment of alcohol use disorder.
AB  - The role of norepinephrine (NE) in the development of alcohol use disorder (AUD)
      has been studied over the past several decades. However, the NE system has been
      largely ignored for many years as a potential target for medication development
      for AUD. More recently, preclinical and clinical studies have demonstrated the
      potential value of targeting NE signaling for developing new pharmacological
      treatments for AUD. This review contributes to a special issue of
      Psychopharmacology focused on promising targets for alcohol addiction.
      Specifically, this review coalesces preclinical and clinical neuroscience that re
      evaluate the noradrenergic system, and in particular the alpha-1 receptor, as a
      potential target for AUD.

PMID- 29460164
TI  - Assessing the risk of type 2 diabetes mellitus among children and adolescents
      with psychiatric disorders treated with atypical antipsychotics: a population
      based nested case-control study.
AB  - To examine the associations between atypical antipsychotic (AAP) exposure and the
      development of type 2 diabetes mellitus (T2DM) in Korean pediatric patients with
      psychiatric disorders, we conducted a nested case-control study using the claims
      data of the National Health Insurance system of Korea between 2010 and 2014. A
      cohort of patients with psychiatric disorders was identified, and enrollment was
      taken as the date of the first psychiatric diagnosis. Cases involved patients
      with a diagnosis of T2DM or prescriptions for glucose lowering drugs after
      enrollment, and the identification of T2DM was defined as the index date. We
      performed a conditional logistic regression analysis for matched case-control
      data to assess associations between AAP exposure and T2DM, and adjusted odds
      ratios (aORs) with 95% confidence intervals (CIs) are presented. From 1,092,019
      patients aged 2-19 years, we identified 20,263 cases with T2DM and 80,043
      controls, matched by sex, age, enrollment date, and primary psychiatric
      diagnosis. After adjusting for comorbidities, psychotropic medication history,
      and the healthcare institution characteristics, the aOR of having T2DM was
      significantly higher in multi-AAP users compared with non-users (aOR 1.89; 95% CI
      1.63-2.20). Particularly high ORs for T2DM were observed in clozapine users
      compared with non-users (aOR 3.47; 95% CI 1.88-6.41). We observed a linear
      relationship between the increase in risperidone dose and the increase in the
      risk of developing T2DM. Our findings suggest a significantly increased risk of
      developing T2DM in child or adolescent patients with psychiatric disorders
      exposed to AAPs compared with those not exposed to AAPs.

PMID- 29460166
TI  - Common and distinct changes of default mode and salience network in schizophrenia
      and major depression.
AB  - Brain imaging reveals schizophrenia as a disorder of macroscopic brain networks.
      In particular, default mode and salience network (DMN, SN) show highly consistent
      alterations in both interacting brain activity and underlying brain structure.
      However, the same networks are also altered in major depression. This overlap in
      network alterations induces the question whether DMN and SN changes are different
      across both disorders, potentially indicating distinct underlying
      pathophysiological mechanisms. To address this question, we acquired T1-weighted,
      diffusion-weighted, and resting-state functional MRI in patients with
      schizophrenia, patients with major depression, and healthy controls. We measured
      regional gray matter volume, inter-regional structural and intrinsic functional
      connectivity of DMN and SN, and compared these measures across groups by
      generalized Wilcoxon rank tests, while controlling for symptoms and medication.
      When comparing patients with controls, we found in each patient group SN volume
      loss, impaired DMN structural connectivity, and aberrant DMN and SN functional
      connectivity. When comparing patient groups, SN gray matter volume loss and DMN
      structural connectivity reduction did not differ between groups, but in
      schizophrenic patients, functional hyperconnectivity between DMN and SN was less
      in comparison to depressed patients. Results provide evidence for distinct
      functional hyperconnectivity between DMN and SN in schizophrenia and major
      depression, while structural changes in DMN and SN were similar. Distinct
      hyperconnectivity suggests different pathophysiological mechanism underlying
      aberrant DMN-SN interactions in schizophrenia and depression.

PMID- 29460167
TI  - Alzheimer disease detection from structural MR images using FCM based weighted
      probabilistic neural network.
AB  - An early intervention of Alzheimer's disease (AD) is highly essential due to the
      fact that this neuro degenerative disease generates major life-threatening
      issues, especially memory loss among patients in society. Moreover, categorizing
      NC (Normal Control), MCI (Mild Cognitive Impairment) and AD early in course
      allows the patients to experience benefits from new treatments. Therefore, it is
      important to construct a reliable classification technique to discriminate the
      patients with or without AD from the bio medical imaging modality. Hence, we
      developed a novel FCM based Weighted Probabilistic Neural Network (FWPNN)
      classification algorithm and analyzed the brain images related to structural MRI
      modality for better discrimination of class labels. Initially our proposed
      framework begins with brain image normalization stage. In this stage, ROI regions
      related to Hippo-Campus (HC) and Posterior Cingulate Cortex (PCC) from the brain
      images are extracted using Automated Anatomical Labeling (AAL) method.
      Subsequently, nineteen highly relevant AD related features are selected through
      Multiple-criterion feature selection method. At last, our novel FWPNN
      classification algorithm is imposed to remove suspicious samples from the
      training data with an end goal to enhance the classification performance. This
      newly developed classification algorithm combines both the goodness of supervised
      and unsupervised learning techniques. The experimental validation is carried out
      with the ADNI subset and then to the Bordex-3 city dataset. Our proposed
      classification approach achieves an accuracy of about 98.63%, 95.4%, 96.4% in
      terms of classification with AD vs NC, MCI vs NC and AD vs MCI. The experimental
      results suggest that the removal of noisy samples from the training data can
      enhance the decision generation process of the expert systems.

PMID- 29460165
TI  - Efficacy and safety of drugs for attention deficit hyperactivity disorder in
      children and adolescents: a network meta-analysis.
AB  - The aim of this study is to gather evidence of head-to-head double-blind
      randomized-controlled trials on the efficacy and safety of available treatments
      for attention deficit hyperactivity disorder (ADHD) in children and adolescents.
      A systematic review was conducted by two independent reviewers in ten electronic
      databases (PROSPERO register CRD42016043239). Methodological quality of included
      studies was evaluated according to the Jadad scale. Network meta-analyses were
      performed including double-blinded head-to-head trials comparing active
      allopathic drugs in patients (0-18 years old) diagnosed with ADHD. The results of
      efficacy and safety of atomoxetine (ATX), bupropion, buspirone (BSP),
      dexamphetamine, edivoxetine (EDX), guanfacine (GXR), lisdexamfetamine (LDX),
      methylphenidate (MPH), mixed amphetamine salts, modafinil, pindolol (PDL),
      reboxetine (RBX), selegiline, and venlafaxine were analyzed using ADDIS software
      v.1.16.5. Forty-eight trials were identified (n = 4169 participants), of which 12
      were used for efficacy analysis and 33 for safety analysis. On the CGI-I scale,
      the analysis revealed that MPH was more effective than ATX and GXR. For the
      safety outcomes, according to drug ranks, LDX was more likely to cause sleep
      disorders (39%) as well as loss of appetite (65%) and behavior problems such as
      irritability (60%). BSP (71%) and EDX (44%) caused less appetite decrease. For
      behavioral effects, PDL was considered safest (50%). For any adverse events, RBX
      (89%) was the safest alternative. The lack of head-to-head trials properly
      reporting outcomes of interest limited some comparisons. Network meta-analysis
      offered a broader overview on the available treatments for ADHD, especially for
      safety issues, and contributes towards evidence gathering and clinical practice
      decisions. A core outcome set for ADHD should be designed to guide the conduction
      and report of clinical trials.

PMID- 29460168
TI  - Multimethodology applied to the evaluation of Healthcare in Brazilian
      municipalities.
AB  - The integration of quantitative indicators with qualitative descriptions of
      context is a noticeable demand from many different scientific disciplines, since
      it contributes to linking theoretical and practical approaches to problem
      solving. Amongst them are the problem structuring methods, systems thinking and
      multimethodology. This work presents a mixed quantitative and qualitative
      methodological approach to aid formulation and structuring of performance
      measurement of health care in 5565 Brazilian municipalities. Data mining and data
      envelopment analysis (DEA) are applied in the context of conceptual mapping, thus
      shedding light on both quantitative and qualitative factors that influence health
      performance. Our aim is to propose a methodology for performance indicators to
      support health care policy making in Brazil, using quantitative indicators.
      However, the approach does not lose track of the role of important qualitative
      factors in the attribution of meaning to performance assessments. The
      methodological and analytical results can strengthen mutual understanding by
      analysts and stakeholders of the problem at hand. Quantitative results allow
      inefficient municipalities to understand the causes of their overall efficiency
      in terms of particular low partial DEA efficiencies combined with high
      deathrates.

PMID- 29460169
TI  - Spatial and Temporal Characteristics of Set-Related Inhibitory and Excitatory
      Inputs from the Dorsal Premotor Cortex to the Ipsilateral Motor Cortex Assessed
      by Dual-Coil Transcranial Magnetic Stimulation.
AB  - The capacity to produce movements only at appropriate times is fundamental in
      successful behavior and requires a fine interplay between motor inhibition and
      facilitation. Evidence in humans indicates that the dorsal premotor cortex (PMCd)
      is involved in such preparatory and inhibitory processes, but how PMCd modulates
      motor output in humans is still unclear. We investigated this issue in healthy
      human volunteers, using a variant of the dual-coil transcranial magnetic
      stimulation (TMS) technique that allows testing the short-latency effects of
      conditioning TMS to the left PMCd on test TMS applied to the ipsilateral
      orofacial primary motor cortex (M1). Participants performed a delayed cued simple
      reaction time task. They were asked to produce a lip movement cued by an
      imperative GO-signal presented after a predictable SET-period, during which TMS
      was applied at different intervals. Results showed that the area of motor evoked
      potentials (MEPs) to test TMS was modulated by conditioning TMS. A transient
      inhibition cortico-bulbar excitability by PMCd stimulation was observed around
      the middle of the SET-period. Conversely, a ramping excitatory effect of PMCd
      stimulation appeared towards the end of the SET-period, as the time of the
      predicted GO-signal approached. The time-course of PMCd-M1 activity scaled to the
      varying SET-period duration. Our data indicate that inhibition and excitation of
      motor output during a delayed reaction time task are two distinct neural
      phenomena. They both originate in PMCd and are conveyed via cortico-cortical
      connections to the ipsilateral M1, where they are integrated to produce harmonic
      fluctuations of motor output.

PMID- 29460170
TI  - [Epidemiology and diagnostic assessment of small renal masses].
AB  - BACKGROUND: The incidence of small renal masses has been rising over the last few
      decades. At the same time, mortality of renal cell carcinoma (RCC) is decreasing.
      These trends can be explained by the availability of improved therapeutic
      measures and the good prognosis of small renal masses (SRM) turning out to be
      histopathologically benign or of low malignancy in many cases. OBJECTIVES: The
      aim of this article is to present epidemiology and diagnostic assessment of SRM.
      MATERIALS AND METHODS: Statistics, basic research, guidelines. RESULTS: The
      incidence of SRM is rising due to the widespread use of imaging techniques such
      as computed tomography (CT), magnetic resonance imaging (MRI), and contrast
      enhanced ultrasound (CEUS). Sensitivity is excellent for CEUS and for CECT in the
      characterization of SRM, while good specificity values can be reached by MRI. For
      characterization of complex cystic renal masses, CEUS has good diagnostic
      accuracy. CONCLUSIONS: Due to improved diagnostic possibilities, SRMs can be
      diagnosed in early asymptomatic stages. As SRM have a good prognosis and often
      are of low malignancy therapy, options should be carefully considered; especially
      in older patients, active surveillance should considered.

PMID- 29460171
TI  - [Minimally invasive versus open prostatectomy for localised prostate cancer].

PMID- 29460172
TI  - Transformative change in Invasion of the Body Snatchers.
AB  - Transformation is a memorable feature of some of the most iconic works of science
      fiction. These works feature characters who begin as humans and change into
      radically different kinds of being. This paper examines transformative change in
      the context of the Invasion of the Body Snatchers movies. I discuss how humans
      should approach the prospect of being body snatched. I argue that we shouldn't
      welcome the transformation even if we are convinced that we will have very
      positive experiences as pod aliens. When considering a transformative change, it
      is appropriate to give priority to your pre-transformation attitudes to potential
      future experiences and achievements over your predicted post-transformation
      attitudes.

PMID- 29460173
TI  - Changes in the axo-glial junctions of the optic nerves of cuprizone-treated mice.
AB  - Demyelination induced by cuprizone in mice has served a useful model system for
      the study of demyelinating diseases, such as multiple sclerosis. Severity of
      demyelination by cuprizone, however, varies across different regions of the
      central nervous system; the corpus callosum is sensitive, while the optic nerves
      are resistant. Here, we investigated the effects of cuprizone on optic nerves,
      focusing on the axo-glial junctions. Immunostaining for sodium channels,
      contactin-associated protein, neurofascins, and potassium channels revealed that
      there were no massive changes in the density and morphology of the axo-glial
      junctions in cuprizone-treated optic nerves. However, when we counted the number
      of incomplete junctional complexes, we observed increased numbers of isolated
      paranodes. These isolated paranodes were immunopositive for both axonal and glial
      membrane proteins, indicating that they were the contact sites between axons and
      glia. These were not associated with sodium channels or potassium channels,
      suggesting the absence of physiological functions. When teased axons from
      cuprizone-treated optic nerves were immunostained, the isolated paranodes were
      found at the internode region of the myelin. From these observations, we conclude
      that cuprizone induces new contacts between axons and myelins at the internode
      region.

PMID- 29460174
TI  - Management of closed sternal incision after bilateral internal thoracic artery
      grafting with a single-use negative pressure system.
AB  - Single-use, closed incision management (CIM) systems offer a practical means of
      delivering negative pressure wound therapy to patients. This prospective study
      evaluates the PrevenaTM Therapy system in a cohort of coronary patients at high
      risk of deep sternal wound infection (DSWI). Fifty-three consecutive patients
      undergoing bilateral internal thoracic artery (BITA) grafting were preoperatively
      elected for CIM with the PrevenaTM Therapy system, which was applied immediately
      after surgery. The actual rate of DSWI in these patients was compared with the
      expected risk of DSWI according to two scoring systems specifically created to
      predict either DSWI after BITA grafting (Gatti score) or major infections after
      cardiac surgery (Fowler score). The actual rate of DSWI was lower than the
      expected risk of DSWI by the Gatti score (3.8 vs. 5.8%, p = 0.047) but higher
      than by the Fowler score (2.3%, p = 0.069). However, while the Gatti score showed
      very good calibration (chi2 = 4.8, p = 0.69) and discriminatory power (area under
      the receiver-operating characteristic curve 0.838), the Fowler score showed
      discrete calibration (chi2 = 10.5, p = 0.23) and low discriminatory power (area
      under the receiver-operating characteristic curve 0.608). Single-use CIM systems
      appear to be useful to reduce the risk of DSWI after BITA grafting. More studies
      have to be performed to make stronger this finding.

PMID- 29460176
TI  - Marrow Fat-a New Target to Treat Bone Diseases?
AB  - PURPOSE OF REVIEW: The goal of this review is to summarize recent findings on
      marrow adipose tissue (MAT) function and to discuss the possibility of targeting
      MAT for therapeutic purposes. RECENT FINDINGS: MAT is characterized with high
      heterogeneity which may suggest both that marrow adipocytes originate from
      multiple different progenitors and/or their phenotype is determined by skeletal
      location and environmental cues. Close relationship to osteoblasts and
      heterogeneity suggests that MAT consists of cells representing spectrum of
      phenotypes ranging from lipid-filled adipocytes to pre-osteoblasts. We propose a
      term of adiposteoblast for describing phenotypic spectrum of MAT. Manipulating
      with MAT activity in diseases where impairment in energy metabolism correlates
      with bone functional deficit, such as aging and diabetes, may be beneficial for
      both. Paracrine activities of MAT might be considered for treatment of bone
      diseases. MAT has unrecognized potential, either beneficial or detrimental, to
      regulate bone homeostasis in physiological and pathological conditions. More
      research is required to harness this potential for therapeutic purposes.

PMID- 29460175
TI  - Preclinical and Translational Studies in Small Ruminants (Sheep and Goat) as
      Models for Osteoporosis Research.
AB  - PURPOSE OF THE REVIEW: This review summarizes research on the use of sheep and
      goats as large animal models of human osteoporosis for preclinical and
      translational studies. RECENT FINDINGS: The most frequent osteoporotic sheep
      model used is the ovariectomized sheep with 12 months post-operatively or more
      and the combined treatment of ovariectomized sheep associated to calcium/vitamin
      D-deficient diet and glucocorticoid applications for 6 months, but other methods
      are also described, like pinealectomy or hypothalamic-pituitary disconnection in
      ovariectomized sheep. The goat model for osteoporosis research has been used in a
      very limited number of studies in osteoporosis research relative to sheep. These
      osteoporotic small ruminant models are applied for biomaterial research, bone
      augmentation, efficacy of implant fixation, fragility fracture-healing process
      improvement, or bone-defect repair studies in the osteopenic or osteoporotic
      bone. Sheep are a recognized large animal model for preclinical and translational
      studies in osteoporosis research and the goat to a lesser extent. Recently, the
      pathophysiological mechanism underlying induction of osteoporosis in
      glucocorticoid-treated ovariectomized aged sheep was clarified, being similar to
      what occurs in postmenopausal women with glucocorticoid-induced osteoporosis. It
      was also concluded that the receptor activator of NF-kappaB ligand was stimulated
      in the late progressive phase of the osteoporosis induced by steroids in sheep.
      The knowledge of the pathophysiological mechanisms at the cellular and molecular
      levels of the induction of osteoporosis in small ruminants, if identical to
      humans, will allow in the future, the use of these animal models with greater
      confidence in the preclinical and translational studies for osteoporosis
      research.

PMID- 29460177
TI  - Simple diverticulectomy is adequate for management of bleeding Meckel
      diverticulum.
AB  - PURPOSE: It is unclear whether simple diverticulectomy, rather than segmental
      bowel resection (SBR), is adequate treatment for gastrointestinal bleeding (GIB)
      secondary to Meckel diverticulum (MD). There is concern that ulcers in the
      adjacent bowel may continue to bleed if only the diverticulum is removed. This
      study seeks to determine if diverticulectomy is satisfactory treatment for
      bleeding MD. METHODS: A multi-institution, retrospective review was performed for
      patients with a diagnosis of MD and GIB who underwent simple diverticulectomy or
      small bowel resection. Exclusion criteria were comorbid surgical conditions and
      other causes of GIB. The primary outcome was post-operative bleeding during the
      initial hospitalization. Secondary outcomes were bleeding after discharge,
      transfusion or additional procedure requirement, re-admission, and overall
      complications. RESULTS: There were 59 patients who met study criteria (42
      diverticulectomy, 17 SBR). One patient in the SBR group had early post-operative
      bleeding (p = 0.288). There was one re-admission (p = 0.288) and three total
      complications in the SBR group (p = 0.021). There were no cases of bleeding or
      other complications in the diverticulectomy group. CONCLUSION: This study
      suggests that simple diverticulectomy is adequate for treatment of GIB caused by
      MD. Furthermore, diverticulectomy appears to have a lower overall complication
      rate.

PMID- 29460178
TI  - A cooperation of catheters and guidewires-based novel remote-controlled vascular
      interventional robot.
AB  - Remote-controlled vascular interventional robots (RVIRs) are being developed to
      increase the overall accuracy of surgical operations and reduce the occupational
      risks of intervening physicians, such as radiation exposure and chronic neck/back
      pain. Several RVIRs have been used to operate catheters or guidewires accurately.
      However, a lack of cooperation between the catheters and guidewires results in
      the surgeon being unable to complete complex surgery by propelling the
      catheter/guidewire to the target position. Furthermore, it is a significant
      challenge to operate the catheter/guidewire accurately and detect their proximal
      force without damaging their surfaces. In this study, we introduce a novel method
      that allows catheters and guidewires to be operated simultaneously in complex
      surgery. Our method accurately captures force measurements and enables precisely
      controlled catheter and guidewire operation. A prototype is validated through
      various experiments. The results demonstrate the feasibility of the proposed RVIR
      to operate a catheter and guidewire accurately, detect the resistance forces, and
      complete complex surgical operations in a cooperative manner.

PMID- 29460179
TI  - A siphonous morphology affects light-harvesting modulation in the intertidal
      green macroalga Bryopsis corticulans (Ulvophyceae).
AB  - MAIN CONCLUSION: The macroalga Bryopsis corticulans relies on a sustained
      protective NPQ and a peculiar body architecture to efficiently adapt to the
      extreme light changes of intertidal shores. During low tides, intertidal algae
      experience prolonged high light stress. Efficient dissipation of excess light
      energy, measured as non-photochemical quenching (NPQ) of chlorophyll
      fluorescence, is therefore required to avoid photodamage. Light-harvesting
      regulation was studied in the intertidal macroalga Bryopsis corticulans, during
      high light and air exposure. Photosynthetic capacity and NPQ kinetics were
      assessed in different filament layers of the algal tufts and in intact
      chloroplasts to unravel the nature of NPQ in this siphonous green alga. We found
      that the morphology and pigment composition of the B. corticulans body provides
      functional segregation between surface sunlit filaments (protective state) and
      those that are underneath and undergo severe light attenuation (light-harvesting
      state). In the surface filaments, very high and sustained NPQ gradually formed.
      NPQ induction was triggered by the formation of transthylakoid proton gradient
      and independent of the xanthophyll cycle. PsbS and LHCSR proteins seem not to be
      active in the NPQ mechanism activated by this alga. Our results show that B.
      corticulans endures excess light energy pressure through a sustained protective
      NPQ, not related to photodamage, as revealed by the unusually quick restoration
      of photosystem II (PSII) function in the dark. This might suggest either the
      occurrence of transient PSII photoinactivation or a fast rate of PSII repair
      cycle.

PMID- 29460180
TI  - Solidification of hydatid cyst fluid with an injectable
      chitosan/carboxymethylcellulose/beta-glycerophosphate hydrogel for effective
      control of spillage during aspiration of hydatid cysts.
AB  - Cystic echinococcosis (CE)/hydatid cyst is one of the most important helminthic
      diseases in the world. The treatment of hydatid cyst ranges from surgical
      intervention to chemotherapy, although the efficacy of chemotherapy is still
      unclear. Postoperative complication which results from the spillage of cysts
      during surgical operation is one of the most important concerns in surgical
      treatment of hydatid cyst. The aim of the current study was to solidify the
      hydatid cyst fluid (HCF) with an injectable and thermosensitive chitosan
      (CS)/carboxymethyl cellulose (CMC)/beta-glycerol phosphate (BGP) hydrogel for
      effective control of spillage during the aspiration of hydatid cysts. Fourier
      transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), water
      uptake, rheological analysis, and Alamar Blue cytotoxicity assay were employed to
      characterize the hydrogel. A five level with three times replication at the
      central point using a central composite design (CCD), which is a response surface
      methodology (RSM), was used to optimize the experimental conditions. Assessment
      of the produced hydrogel showed that the intermolecular interactions of amino
      groups of chitosan and hydrogen groups of CMC were correctively established and
      appreciable swelling with a good strength was obtained. Hydrogels morphology had
      a porous structure. Rheological analysis showed that CS/CMC/BGP blends had a
      phase transition (32-35  degrees C) of sol-gel close to the body temperature.
      Alamar Blue cytotoxicity assay showed that CS (1.75%)/CMC (1.4%)/BGP (2.9%) had
      IC50 values of 0.598, 0.235 and 0.138 (ug/uL) for 24, 48 and 72 h, which
      indicated that the produced polymer solution had no significant cytotoxic effect
      for human fibroblast cell line. In vitro injection of the polymer solution of
      CS/CMC/BGP with CS/CMC ratio of 1.75/1.4 was done on HCF (1 mL polymer solution
      to 3 mL of HCF) at 37  degrees C with a final concentration of 2.9% for BGP
      resulting in solidification of HCF in less than 45 min.

PMID- 29460181
TI  - Immunoisolation of stem cells by simultaneous encapsulation and PEGylation.
AB  - Today, cell therapy is known as an important tool in the treatment of chronic
      diseases where cells lose their normal function. Immunoisolation systems using
      microencapsulation or PEGylation have been developed to evade the problem of
      rejection by the immune system. The aim of the present study was to investigate a
      combination of microencapsulation and PEGylation methods in coating mouse
      embryonic stem cells (mESCs) to determine its effect in reducing the host's
      immune response. Therefore, methoxy polyethylene glycol (mPEG) binding on
      alginate-trimethyl chitosan (TMC) microcapsules was investigated using FTIR.
      Furthermore, survival of the microencapsulated mESCs was confirmed using AO/PI
      staining and MTT assays. In addition, the effect of mESCs co-cultured with
      foreign lymphocytes was evaluated. Overall, interleukin-2 (IL-2) secretions as a
      response of the immune system revealed that mESCs microencapsulation in alginate
      TMC-PEG, reduced the immune system response. The results suggested that IL-2
      secretion was reduced to 62% at seventh day.

PMID- 29460182
TI  - The Time Point-Specific Effect of Beta-Adrenergic Blockade in Attenuating High
      Fat Diet-Induced Obesity and Bone Loss.
AB  - We aimed to clarify the key factor determining the effect of beta blocker
      attenuating high fat diet- induced obesity and bone loss. Six-week-old C57BL/6
      male mice were assigned to groups reflecting different relative onset of obesity
      and beta blocker administration, different diet (control vs. high fat), and
      treatment (vehicle vs. beta blocker: propranolol). Mice in Group 1 were fed a
      control diet (CON) or high fat diet (HIGH) with vehicle or propranolol for 12
      weeks. Mice in Group 2 were fed a CON or HIGH without pharmaceutical treatment
      for the first 12 weeks, followed by another 12 weeks of treatment with vehicle or
      propranolol. Mice in Group 3 were fed a CON without pharmaceutical treatment for
      the first 12 weeks, followed by stratification into diet-based subgroups and
      another 12 weeks of treatment with vehicle or propranolol. Propranolol attenuated
      the HIGH-induced increase in body weight/fat mass in Group 1 mice and in Group 3
      mice, but not in Group 2 mice. Propranolol mitigated HIGH-induced reduction in
      femoral trabecular bone mineral density and bone architecture deterioration in
      Group 1 mice but not in Group 2 mice. HIGH feeding in Group 3 did not compromise
      skeletal integrity. Taken together, propranolol attenuates HIGH-induced body
      weight increases while weight gain is in progress but not once obesity has
      already been established. HIGH feeding during the growth period results in
      compromised bone mass/architecture; which can be attenuated by propranolol
      administration during the growth period, but not by propranolol administration
      after obesity has already been established.

PMID- 29460183
TI  - Nutritional history does not modulate hepatic oxidative status of European sea
      bass (Dicentrarchus labrax) submitted to handling stress.
AB  - The aim of the present study was to assess the impact of an acute handling stress
      on hepatic oxidative status of European sea bass (Dicentrarchus labrax) juveniles
      fed diets differing in lipid so urce and carbohydrate content. For that purpose,
      four diets were formulated with fish oil (FO) and vegetable oils (VO) as lipid
      source and with 20 or 0% gelatinized starch as carbohydrate source. Triplicate
      groups of fish with 74 g were fed each diet during 13 weeks and then subjected to
      an acute handling stress. Stress exposure decreased hematocrit (Ht) and
      hemoglobin (Hb) levels. Independent of dietary treatment, stress exposure
      increased hepatic lipid peroxidation (LPO). Stressed fish exhibited lower glucose
      6-phosphate dehydrogenase (G6PD), catalase (CAT), and superoxide dismutase (SOD)
      activities, independent of previous nutritional history. In the VO groups, stress
      exposure increased glutathione peroxidase (GPX) activity. Diet composition had no
      effect on Ht and Hb levels. In contrast, dietary carbohydrate decreased hepatic
      LPO and CAT activity and increased glutathione reductase (GR) and G6PD
      activities. Dietary lipids had no effect on LPO. Fish fed the VO diets exhibited
      higher G6PD activity than fish fed the FO diets. In conclusion, dietary
      carbohydrates contributed to the reduction of oxidative stress in fish. However,
      under the imposed handling stress conditions, liver enzymatic antioxidant
      mechanisms were not enhanced, which may explain the overall increased oxidative
      stress.

PMID- 29460184
TI  - Circulatory white spot syndrome virus in South-West region of Bangladesh from
      2014 to 2017: molecular characterization and genetic variation.
AB  - White Spot Syndrome Virus (WSSV), the etiological agent of White Spot Disease
      (WSD) is a major impediment for shrimp aquaculture in the worldwide. A critical
      threshold level of WSSV load in infected shrimp is an important trait for disease
      manifestation and WSSV transmission in cultured shrimp and subsequently make
      outbreaks. The present study investigated 120 naturally infected cultured shrimp
      samples by SYBR Green based qPCR assay for WSD diagnosis and quantification of
      WSSV load. Among them, 94 samples resulted a variable count of WSSV load ranging
      from 2.1 * 108 to 2.64 * 1014 copies/g of shrimp tissue. The severity of WSSV
      infection was assessed based on the established critical threshold load of WSSV
      in shrimp tissue. Compared to the established critical threshold value of WSSV
      load in shrimp tissue, our findings showed the horrifying scenario of the
      severity of WSSV infection in cultured shrimps of Bangladesh that was found to be
      above the critical limit to initiate an outbreak in the Bangladeshi shrimp
      aquaculture industry. The latest phylogenetic pattern was altered from the former
      monophyletic history among WSSVs of Bangladesh due to a variation at 500th
      nucleotide of VP28 coding gene. Viruses characterized from recent outbreaks in
      2015 and 2017 displayed amino acid substitution at position 167 (G->E) on the
      surface of VP28 protein which has demonstrated the probable replacement of
      indigenous virus pool. Therefore, it is imperative to take initiative for the
      management and prevention of WSSV outbreak to sustain shrimp aquaculture in South
      West region of Bangladesh.

PMID- 29460185
TI  - Influences of environmental factors on macroinvertebrate assemblages: differences
      between mountain and lowland ecoregions, Wei River, China.
AB  - Key environmental factors and the mechanisms of their influence on the
      physicochemical habitats and macroinvertebrate communities of streams may vary
      among ecoregions. We studied the differences in environmental (land use and
      physicochemical) factors and the mechanisms of their influence on
      macroinvertebrate assemblages between mountain and lowland ecoregions in central
      China. We applied generalized linear models to identify key environmental factors
      that influence macroinvertebrate metrics consisting of taxa richness,
      Ephemeroptera, Plecoptera, and Trichoptera (EPT) taxa, percentages of EPT and
      intolerant individuals, and the Shannon-Wiener diversity index. Environmental
      factors and macroinvertebrate metrics significantly differed between the
      ecoregions. Mountain streams had significantly lower nutrients and %silt, but had
      twice higher total taxa richness than lowland streams. Watershed land uses were
      key drivers that influenced the physical habitat in the mountain ecoregion and
      were the main drivers that influenced both physical and chemical conditions in
      the lowland ecoregion. Correspondingly, watershed scale land uses, as well as
      physical and chemical variables, explained more variance in macroinvertebrate
      metrics than local-scale land uses in both mountain and lowland ecoregions. The
      overall biological variation was explained better by watershed-scale than by
      reach-scale land uses, whereas the spatial scale over which land use and
      physicochemical variables influence streams varied across ecoregions. Our results
      suggest that better landscape planning should be adopted for watershed management
      to improve water quality and physical habitat, and thus the conservation and
      restoration of macroinvertebrate biodiversity.

PMID- 29460186
TI  - Non-sebaceous lymphadenoma of the lacrimal gland: first report of a new
      localization.

PMID- 29460187
TI  - Subcritical n-hexane/isopropanol extraction of lipid from wet microalgal pastes
      of Scenedesmus obliquus.
AB  - Subcritical co-solvents of n-hexane/isopropanol were primarily utilized to
      extract lipid from wet microalgal pastes of Scenedesmus obliquus. The effects of
      key operational parameters were investigated, and the optimal parameters were
      obtained: solvent ratio of n-hexane to isopropanol was 3:2 (V:V), phase ratio of
      co-solvents to microalgal biomass was 35:1 (mL:g), reactor stirring speed was 900
      rpm, extraction time was 60 min. Additional pretreatment with acid, ultrasonic
      and microwave as well as enhanced subcritical pressure/heating treatments were
      also applied to further study their effects on lipid extraction. The results
      showed that the lipid recovery rate with acid pretreatment was 8.6 and 6.2%
      higher than ultrasonic and microwave pretreatment; the optimum enhanced
      subcritical condition was 55  degrees C with atmospheric pressure. Under optimal
      operating conditions, the lipid and FAME yield were 13.5 and 7.2%, which was 82.6
      and 135.1% higher than the traditional method. The results indicated that the
      subcritical n-hexane/isopropanol extraction process had promising application
      potential.

PMID- 29460188
TI  - Motivational Factors in Women Seeking Augmentation Mammoplasty Across Different
      Age Groups: A Cross-Sectional Survey.
AB  - BACKGROUND: Augmentation mammoplasty is one of the most common esthetic
      procedures worldwide. A wide range of motivations leads women to undergo this
      procedure, among them socioeconomic status and age group. The aim of this study
      was to identify the motivation spectrum for augmentation mammoplasty through
      different age groups. METHODS: We conducted a cross-sectional prospective survey
      given to Israeli women seeking augmentation mammoplasty consults in a hospital
      and private clinic settings, using a 17-item Motivation for Augmentation
      questionnaire. Three motivation domains were examined: appearance, sexuality and
      social. Study participants were divided into three age groups: 18-29, 30-39 and
      over 40 years. RESULTS: A total of 101 women participated in the study.
      Motivations were rated similar among all age groups. Appearance and sexuality
      domains were rated significantly higher compared with the social domain
      throughout all age groups (3.28 +/- 0.91 and 3.15 +/- 1.03 vs. 1.88 +/- 1.16, p <
      0.001, respectively). CONCLUSIONS: Motivations in Israeli women seeking breast
      augmentation do not change with age. The desire to improve one's appearance and
      sexuality is more prominent than improving social and work status. 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- 29460189
TI  - Response to Time-Out Among Preschoolers with Externalizing Behavior Problems: The
      Role of Callous-Unemotional Traits.
AB  - This study examined the role of callous-unemotional (CU) traits in preschoolers
      with externalizing behavior problems (EBP) and their response to time-out (TO).
      One hundred ninety preschoolers (76% boys, Mage = 4.92) with at-risk/clinically
      elevated levels of EBP participated in an 8-week summer treatment program (STP
      PreK). Total number of minutes spent daily in TO for intentional aggression (IA)
      and repeated non-compliance (RNC) were recorded during the initial (T1) and final
      (T2) phases of the STP-PreK. After accounting for severity of EBP and levels of
      TO at T1, higher levels of CU traits predicted greater total levels of TO at T2.
      An interaction also emerged between symptoms of oppositional defiant disorder
      (ODD) and CU traits in predicting IA. Specifically, greater ODD symptoms
      predicted fewer number of IA related TO at T2, but only for children with low CU
      traits. Implications for treatment are discussed.

PMID- 29460190
TI  - Quantitative analysis of phantom studies of 111In and 68Ga imaging of
      neuroendocrine tumours.
AB  - BACKGROUND: Nuclear medicine imaging of neuroendocrine tumours is performed
      either by SPECT/CT imaging, using 111In-octreotide or by PET/CT imaging using
      68Ga-radiolabelled somatostatin analogs. These imaging techniques will give
      different image quality and different detection thresholds for tumours, depending
      on size and activity uptake. The aim was to evaluate the image quality for 111In
      SPECT and 68Ga-PET imaging, i.e. the smallest volume possible to visualize for
      different source-to-background activity ratios. The accuracy of quantification of
      lesion volume and activity was also investigated to develop an objective
      evaluation for radionuclide therapy eligibility. The phantom study was performed
      using the NEMA IEC Body Phantom with six hot spheres having inner diameters of
      10, 13, 17, 22, 28, and 37 mm, filled with either 68Ga or 111In with sphere-to
      background ratios (SBRs) of no background activity, 5:1, 2.5:1, and 1.25:1.
      Activity ratios of 1.25:1 and 2.5:1 are clinically found for lesions close to the
      liver and spleen. Clinical acquisition and reconstruction protocols were applied.
      Line profiles were drawn to evaluate the smallest detectable volume within a
      given SBR. Recovery curves based on threshold-based VOIs, threshold-based VOIs
      adapted to the background and CT-based ROIs were obtained for all SBRs and sphere
      diameters, allowing for quantification. RESULTS: The 10-mm sphere was not
      possible to detect in SPECT images. It was detectable in PET images for SBRs of
      2.5:1 and higher. In a background corresponding to the activity uptake in the
      liver, spheres larger than 22-37 mm were detectable in the 111In-SPECT images and
      spheres larger than 13-22 mm were detectable in the 68Ga-PET images. The maximum
      activity concentration was accurately quantified for spheres larger than 22 mm in
      the PET images; however, the quantification was impaired by sphere size and
      background activity. CONCLUSIONS: It was not possible to detect the 10-mm sphere
      in any of the SPECT images. In a background corresponding to the activity uptake
      in the liver, spheres larger than approximately 30 mm were visible in the 111In
      SPECT images and spheres larger than approximately 17 mm were visible in the 68Ga
      PET images. Sphere diameter and background activity strongly affect the
      possibility of a correct quantification.

PMID- 29460191
TI  - Multivariate analysis and health risk assessment of heavy metal contents in
      foodstuffs of Durban, South Africa.
AB  - This study presented a comprehensive analysis of heavy metal contents in
      foodstuffs and the associated health risk for the residential population in
      Durban, South Africa. The concentrations of elements in fruits and vegetables,
      respectively, were (in mg kg-1 dry weight) Cu, 0.52-1.47 and 0.27-2.25; Zn, 0.30
      3.05 and 0.56-6.24, Fe, 1.70-22.60 and 0.73-44.90; Mn, 0.37-28.50 and 0.67-13.70;
      Cr, 0.47-1.47 and 0.37-3.06; Ni 0.03-1.14 and 0.11-2.5;, and Pb, 1.52-3.45 and
      1.57-4.52. Multivariate analysis revealed that pineapple in fruits and turnip and
      carrot in vegetables contained remarkable components of trace metals. The target
      hazard quotient (THQ) values for heavy metals were arranged in the order of Pb >
      Mn > Cu > Ni > Zn > Cr. No potential health risks were reported for individual
      elements over a lifetime of exposure, except children's exposure to Mn in
      pineapple and Pb in banana, orange small, guava, grape green, grape red, yellow
      orange, and kiwifruit. The total THQ due to the dietary intake of multiple metals
      demonstrated unsafe limits in banana, pineapple, orange small, guava, grape
      green, grape red, yellow-orange, kiwifruit, and spinach leaf for children and
      pineapple for adults.

PMID- 29460192
TI  - Aberrant Expression of Some Circulating miRNAs in Childhood Acute Lymphoblastic
      Leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is a heterogeneous cancer commonly affecting
      children due to dysregulation of miRNA expression. In the current study, authors
      investigated the expression profile for miRNA-125b-1 and miRNA-203 among
      childhood ALL. Blood samples were collected from newly diagnosed childhood ALL
      and healthy control children. The expression profile for candidate miRNAs was
      detected using quantitative RT-PCR analysis. Statistical analysis were performed
      using receiver operating characteristic curve (ROC) to examine the diagnostic
      efficacy of the two miRNA and their levels among ALL clinicopathological factors
      and phenotypes. The median expression level for miRNA-125b-1 was significantly
      high in childhood ALL; while miRNA-203 level was significantly low in childhood
      ALL as compared to control ones. MiRNA-125-1 reported significant increase in T
      ALL as compared to other ALL phenotypes. Median miRNA-203 level was high in T-ALL
      followed by pre-B-ALL although no significant difference was reported.
      Clinicopathological factors did not emphasize significance with either detected
      miRNAs. Using ROC curve the diagnostic efficacy was significant with an area
      under the curve 0.858 for miRNA-125b-1 (83.72, 100%) and 0.878 for miRNA-203
      (97.67, 86.96%). The combination of the two key miRNAs revealed absolute
      sensitivity (100%). MiRNA-125b-1 and miRNA-203 can be useful molecular markers
      for diagnosis of ALL. Further studies with large cohort are warranted to validate
      these results.

PMID- 29460193
TI  - Use of compression garments by women with lymphoedema secondary to breast cancer
      treatment.
AB  - PURPOSE: This aim of this study was to determine the use of compression garments
      by women with lymphoedema secondary to breast cancer treatment and factors which
      underpin use. METHODS: An online survey was distributed to the Survey and Review
      group of the Breast Cancer Network Australia. The survey included questions
      related to the participants' demographics, breast cancer and lymphoedema medical
      history, prescription and use of compression garments and their beliefs about
      compression and lymphoedema. Data were analysed using principal component
      analysis and multivariable logistic regression. RESULTS: Compression garments had
      been prescribed to 83% of 201 women with lymphoedema within the last 5 years,
      although 37 women had discontinued their use. Even when accounting for severity
      of swelling, type of garment(s) and advice given for use varied across
      participants. Use of compression garments was driven by women's beliefs that they
      were vulnerable to progression of their disease and that compression would
      prevent its worsening. Common reasons given as to why women had discontinued
      their use included discomfort, and their lymphoedema was stable. Participant
      characteristics associated with discontinuance of compression garments included
      their belief that (i) the garments were not effective in managing their
      condition, (ii) experienced mild-moderate swelling and/or (iii) had experienced
      swelling for greater than 5 years. CONCLUSION: The prescription of compression
      garments for lymphoedema is highly varied and may be due to lack of underpinning
      evidence to inform treatment.

PMID- 29460194
TI  - Spiritual well-being associated with personality traits and quality of life in
      family caregivers of cancer patients.
AB  - PURPOSE: This study focuses on the spiritual well-being (SWB) of the family
      caregivers of cancer patients, examining the relationship with personality traits
      and quality of life (QoL) in palliative and curative care settings. METHODS: All
      participants (n = 199) underwent the following self-report questionnaires: the
      Structural Analysis of Social Behavior (SASB)-Form A, the SWB Index, and the
      Medical Outcomes Study Short Form (SF-36). SWB scores were dichotomized at a
      cutoff corresponding to the 75th percentile. STATISTICAL ANALYSIS: Student's t
      test or by chi squared tests to compare high and low SWB and multivariate linear
      regression to estimate relations between SWB, SASB clusters (Cl), and QoL
      dimensions. RESULTS: Caregivers with high SWB reported significantly better
      scores than low SWB caregivers in the following SF-36 subscales: bodily pain (p =
      0.035), vitality (p < 0.001), social activities (p < 0.001), mental health
      subscales (p < 0.001), and standardized mental component (p < 0.001) in the SASB
      Cl2 (p < 0.005), SASB Cl7 (p = 0.007), and SASB Cl8 (p < 0.001). Multivariate
      linear regression was performed with vitality, standardized mental component,
      SASB Cl2, SASB Cl7, and SASB Cl8. Greater SWB is associated with greater vitality
      (p < 0.001), mental standardized component (p < 0.001), and SASB Cl2 (p < 0.001),
      but lower SASB Cl7 (p < 0.05) and SASB Cl8 (p < 0.05); palliative care is
      associated with greater SASB Cl8 (p < 0.05) and lower standardized mental
      component compared with the caregivers in active care. CONCLUSIONS: This study
      points out that caregivers who experience low SWB have a poorer QoL and more
      problematic intrapsychic aspects of personality, such as low self-acceptance of
      their own emotions, are self-refusing and unable to be in contact with their own
      feelings. This suggests that spirituality could be a source of strength and a
      potential avenue for therapeutic intervention.

PMID- 29460195
TI  - High risk for obstructive sleep apnea hypopnea syndrome predicts new onset atrial
      fibrillation after cardiac surgery: a retrospective analysis.
AB  - PURPOSE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is highly prevalent in
      patients undergoing coronary artery bypass surgery (CABG). OSAHS is a risk factor
      for the development of atrial fibrillation (AF), but the risk of AF in patients
      who are high risk for OSAHS is unclear. METHODS: A retrospective study was
      conducted on consecutive patients undergoing CABG from 2013 to 2015 without AF
      pre-operatively. Patients were categorized as low risk for OSAHS, high risk for
      OSAHS, or diagnosed OSAHS based on medical records review. All diagnosed OSAHS
      patients were on active treatment with positive airway pressure. Outcomes
      assessed were postoperative AF (POAF), postoperative length of stay, re
      intubation, in-hospital mortality, and cost of hospitalization. RESULTS: Out of
      209 eligible patients, 66.5% were low-risk for OSAHS, 18.7% high-risk for OSAHS,
      and 14.8% diagnosed/treated for OSAHS. POAF developed in 96 patients (45.9%) with
      greater frequency in high-risk OSAHS patients (69.2% high risk, 41.9% low risk,
      40.3% diagnosed/treated, p = 0.01). In analyses adjusted for age, sex, ethnicity
      and comorbidities, high risk for OSAHS was associated with 2.9 greater odds (95%
      CI [1.2, 7.3], p = 0.02) for POAF while diagnosed/treated OSAHS was not
      associated with elevated risk (OR = 1.4, 95% CI [0.6, 3.6], p = 0.50) compared to
      patients at low risk for OSAHS. CONCLUSIONS: High risk for OSAHS is an
      independent predictor for POAF in patients undergoing CABG. In contrast, patients
      diagnosed and treated for their OSAHS are not at elevated risk of POAF. These
      findings support evaluation of a standardized OSAHS screening and treatment
      program as part of the pre-operative evaluation for elective CABG.

PMID- 29460196
TI  - A comparative study of biotechnological approaches for producing valuable
      flavonoids in Prosopis farcta.
AB  - The callus and hairy root cultures of Prosopis farcta were established to develop
      effective strategies to enhance its valuable and medicinally important flavonoid
      compounds. For callus induction, the hypocotyl, cotyledon and shoot explants were
      subjected to different plant hormones, naphthalene acetic acid (NAA),
      benzylaminopurine (BAP), kinetin and dichlorophenoxyacetic acid (2,4-D). Greater
      callus induction was obtained from hypocotyl explants on MS medium containing 3.0
      mg L-1 NAA + 2.0 mg L-1 BAP. With the addition of 0.5 mg L-1 asparagine to this
      medium, the maximum callus growth was achieved. Hairy root culture of P. farcta
      was performed using transformation of different explants with strains of
      Agrobacterium rhizogenes LBA9404, A4, AR15834. The AR15834 strain was more
      effective for hairy root induction where it caused hairy root formation on 59% of
      the infected cotyledon explants. We compared profiles of flavonoids isolated from
      seedling roots, hairy roots, and callus cultures of P. farcta. The colorimetric
      analysis showed that the content of total flavonoids of hairy roots was 1.54 and
      2.52 times higher than in seedling roots and callus, respectively. The presence
      of flavonoids was verified by LC/MS in positive ion mode. The results showed that
      flavonoid composition was different in the roots and callus. Naringenin was the
      major constituent in callus, whereas resveratrol, quercetin and myricetin were
      the most abundant compounds found in hairy roots. The main objective of this
      research was to establish hairy roots in P. farcta to synthesize flavonoids at
      levels comparable to in vitro-grown roots. The present study also opens up a way
      to further improve the production of pharmaceutically valuable flavonoids and to
      produce desired metabolites using the hairy root culture system.

PMID- 29460197
TI  - Anti inflammatory effect of asiaticoside on human umbilical vein endothelial
      cells induced by ox-LDL.
AB  - Early diagnosis and changes associated with atherosclerosis are crucial in
      clinical medicine. However, atherosclerosis is a multifactorial disease.
      Asiaticoside (AA), a triterpenoid derived from Centella asiatica, has anti
      inflammatory activity. Endothelium-derived nitric oxide is important in
      modulating vascular tone in a distinct vessel size-dependent manner; it plays a
      dominant role in conduit arteries and endothelium-dependent hyperpolarisation in
      resistance vessels. This study evaluated the effects of AA administration on
      human umbilical endothelial cells with oxidised low-density lipoprotein-induced
      inflammation. We measured the levels of intercellular adhesion molecule-1 (ICAM
      1) and vascular cell adhesion molecule-1 (VCAM-1). Our results indicated that 10
      30 MUM AA modulated endothelial hyper permeability, adenosine triphosphate
      levels, ICAM-1 expression, VCAM-1 expression, E-selectin levels, and PECAM-1
      expression to 90% (p < 0.005), 80% (p < 0.05), 105% (p < 0.01), 65% (p < 0.005),
      70% (p < 0.05), and 105% (p < 0.01), respectively. Taken together, our data
      suggest that AA inhibits the augmentation of endothelial permeability, thus
      preventing the early events of atherosclerosis.

PMID- 29460198
TI  - Collaborative environmental DNA sampling from petal surfaces of flowering cherry
      Cerasus * yedoensis 'Somei-yoshino' across the Japanese archipelago.
AB  - Recent studies have shown that environmental DNA is found almost everywhere.
      Flower petal surfaces are an attractive tissue to use for investigation of the
      dispersal of environmental DNA in nature as they are isolated from the external
      environment until the bud opens and only then can the petal surface accumulate
      environmental DNA. Here, we performed a crowdsourced experiment, the "Ohanami
      Project", to obtain environmental DNA samples from petal surfaces of Cerasus *
      yedoensis 'Somei-yoshino' across the Japanese archipelago during spring 2015. C.
      * yedoensis is the most popular garden cherry species in Japan and clones of this
      cultivar bloom simultaneously every spring. Data collection spanned almost every
      prefecture and totaled 577 DNA samples from 149 collaborators. Preliminary
      amplicon-sequencing analysis showed the rapid attachment of environmental DNA
      onto the petal surfaces. Notably, we found DNA of other common plant species in
      samples obtained from a wide distribution; this DNA likely originated from the
      pollen of the Japanese cedar. Our analysis supports our belief that petal
      surfaces after blossoming are a promising target to reveal the dynamics of
      environmental DNA in nature. The success of our experiment also shows that
      crowdsourced environmental DNA analyses have considerable value in ecological
      studies.

PMID- 29460199
TI  - Delayed selfing ensures reproductive assurance in Utricularia praeterita and
      Utricularia babui in Western Ghats.
AB  - Numerous bladderwort (Utricularia) species are distributed worldwide, but their
      reproductive biology is rarely investigated. Bladderworts are known to depend on
      tiny organisms to meet a significant proportion of their energy requirement by
      trapping them in bladders. However, information on the extent of their reliance
      on insects for pollination success is limited. We examined the reproductive
      strategy of two Utricularia species viz. Utricularia praeterita and U. babui,
      endemic to Western Ghats, India. The main aspects of the investigation involved
      floral biology, breeding system, pollination mechanism, and reproductive success.
      Flowers of both the species are structured for outbreeding through entomophilous
      floral suites, herkogamy, protandrous dichogamy and sensitive lobes of the
      stigma. With nearly 65% natural fruit-set, both the species appeared to be
      sufficiently open-pollinated. However, pollinators failed to show in plants of U.
      praeterita while in U. babui there was an apparent mismatch between the extent of
      fruit-set and pollinator visits. The study demonstrated that in the
      absence/insufficient visits of pollinators, the two species resort to autonomous
      selfing. In U. babui, denser patches of plants appeared to be crucial for
      attracting the pollinators. Both species are self-compatible, and reproductive
      success is predominantly achieved by delayed autonomous selfing. The sensitive
      stigma in the species fails to prevent selfing due to diminished herkogamy during
      the late anthetic stages. It is inferred that in the pollinator-limited
      environment, delayed selfing contributes to absolute natural fecundity in U.
      praeterita, while it produces a mixed progeny in U. babui.

PMID- 29460200
TI  - A novel high-sensitivity assay to detect a small fraction of mutant IDH1 using
      droplet digital PCR.
AB  - Detection of mutations in the isocitrate dehydrogenase 1 (IDH1) gene is useful
      for accurate diagnosis of lower grade gliomas, as described in the 2016 World
      Health Organization classification of tumors of the central nervous system.
      Conventional analysis tools, including Sanger DNA sequencing and
      immunohistochemistry, might fail to detect a small fraction of mutant IDH1 owing
      to their limited sensitivity. Considering that lower grade gliomas are
      infiltrative in nature, a highly sensitive detection assay for IDH1 mutation is
      required for their accurate diagnosis. In this study, we successfully established
      a droplet digital PCR (ddPCR) system to detect a small fraction of IDH1 mutation.
      We could detect 0.05% of mutant IDH1 allele in 30 ng DNA. Using this assay, we
      could detect a small fraction of mutant IDH1 in a glioma case, identified as a
      wildtype tumor according to the conventional assays. Additionally, in a small
      amount of DNA derived from the cerebrospinal fluid, we could detect an IDH1
      mutation. In conclusion, the ddPCR system is useful to identify a small fraction
      of IDH1 mutation in diffuse infiltrative gliomas. This might be useful for
      precision medicine of these gliomas in the near future and also for the non
      invasive diagnosis of these gliomas.

PMID- 29460201
TI  - Patients with refractory ascites treated with alfapump(r) system have better
      health-related quality of life as compared to those treated with large volume
      paracentesis: the results of a multicenter randomized controlled study.
AB  - BACKGROUND: Refractory ascites (RA) is a complication of cirrhosis which is
      treated with large volume paracentesis (LVP) as the standard of care. Alfapump(r)
      system is a fully implantable pump system which reduces the need for LVP. The aim
      was to assess health-related quality of life (HRQL) in patients treated with
      alfapump(r) versus LVP. METHODS: The data were collected in a multicenter open
      label randomized controlled trial (clinicaltrials.gov #NCT01528410). Subjects
      with cirrhosis Child-Pugh class B or C accompanied by RA were randomized to
      receive alfapump(r) or LVP. The SF-36v2 and CLDQ scores were compared between the
      two treatment arms at screening and monthly during treatment. RESULTS: Of 60
      subjects randomized, HRQL data were available for 58 (N = 27 received alfapump(r)
      and N = 31 received LVP only). At baseline, no differences were seen between the
      treatment arms (all p > 0.05): age 61.9 +/- 8.4, 79.3% male, MELD scores 11.7 +/-
      3.3, 85.2% Child-Pugh class B, 70.7% had alcoholic cirrhosis. The mean number of
      LVP events/subject was lower in alfapump(r) than LVP (1.1 vs. 8.6, p < 0.001).
      The HRQL scores showed a moderate improvement from the baseline levels in
      subjects treated with alfapump(r) (p < 0.05 for abdominal and activity scores of
      CLDQ) but not with LVP (all one-sided p > 0.05) in the first 3 months.
      Multivariate analysis showed that treatment with alfapump(r) was independently
      associated with better HRQL at 3 months (total CLDQ score: beta = 0.67 +/- 0.33,
      p = 0.05). CONCLUSION: As compared to LVP, the use of alfapump(r) system is
      associated with both a reduction in the number of LVP events and improvement of
      health-related quality of life.

PMID- 29460203
TI  - Time Is Cerebellum.
AB  - The cerebellum characteristically has the capacity to compensate for and restore
      lost functions. These compensatory/restorative properties are explained by an
      abundant synaptic plasticity and the convergence of multimodal central and
      peripheral signals. In addition, extra-cerebellar structures contribute also to
      the recovery after a cerebellar injury. Clinically, some patients show remarkable
      improvement of severe ataxic symptoms associated with trauma, stroke, metabolism,
      or immune-mediated cerebellar ataxia (IMCA, e.g., multiple sclerosis,
      paraneoplastic cerebellar degeneration, gluten ataxia, anti-GAD65 antibody
      associated cerebellar ataxia). However, extension of a cerebellar lesion can
      impact upon the fourth ventricle or the brainstem, either by direct or indirect
      mechanisms, leading to serious complications. Moreover, cerebellar reserve itself
      is affected by advanced cell loss and, at some point of disease progression,
      deficits become irreversible. Such phase transition from a treatable/restorable
      state (the reserve is still sufficient) to an untreatable state (the reserve is
      severely affected) is a loss of therapeutic opportunity, highlighting the need
      for early treatment during the restorable stage. Based on the motto of "Time is
      Brain," a warning that stresses the importance of early therapeutic intervention
      in ischemic diseases, we propose "Time is Cerebellum" as a principle in the
      management of patients with cerebellar diseases, especially immune ataxias whose
      complexity often delay the therapeutic intervention. Indeed, this concept should
      not be restricted to ischemic cerebellar diseases. We argue that every effort
      should be made to reduce the diagnostic delay and to initiate early therapy to
      avoid the risk of transition from a treatable state to an irreversible condition
      and an associated accumulation of disability. The myriad of disorders affecting
      the cerebellum is a challenging factor that may contribute to irreversible
      disability if the window of therapeutic opportunity is missed.

PMID- 29460202
TI  - Clinicopathological significance of baseline T2-weighted signal intensity in
      functional pituitary adenomas.
AB  - PURPOSE: To assess baseline T2-weighted signal intensity (T2-WSI) of functional
      pituitary adenomas (FPA), and to investigate the relationship of baseline T2-WSI
      with clinical features, histopathological granulation patterns, and response to
      treatment in patients with acromegaly, prolactinoma and Cushing's disease (CD).
      METHODS: Somatotroph adenomas (n = 87), prolactinomas (n = 78) and corticotroph
      adenomas (n = 29) were included in the study. Baseline T2-WSI findings (grouped
      as hypo-, iso- and hyperintense) were compared with hormone levels, tumor
      diameter, granulation patterns and response to treatment. RESULTS: Somatotroph
      adenomas were mostly hypointense (53%), prolactinomas were dominantly
      hyperintense (55%), and corticotroph adenomas were generally hyperintense (45%).
      Hyperintense somatotroph adenomas were larger in size with sparsely granulated
      pattern and tumor shrinkage rate was lower after somatostatin analogues (SSA) (p
      = 0.007, p = 0.035, p = 0.029, respectively). T2 hypointensity was related with
      higher baseline IGF-1% ULN (upper limit of normal) levels and a better response
      to SSA treatment (p = 0.02, p = 0.045, respectively). In female prolactinomas,
      hyperintensity was correlated with a smaller adenoma diameter (p = 0.001).
      Hypointense female prolactinomas were related to younger age at diagnosis, higher
      baseline PRL levels and dopamine agonist (DA) resistance (p = 0.009, p = 0.022, p
      < 0.001, respectively). Hyperintense corticotroph adenomas were related to larger
      adenoma size and sparsely granulated pattern (p = 0.04, p = 0.017, respectively).
      There was no significant difference in the recurrence with T2WSI in CD.
      CONCLUSION: Baseline hypointense somatotroph adenomas show a better response to
      SSA, whereas hypointensity was related to DA resistance in female prolactinomas.

PMID- 29460204
TI  - Development of a Psychiatric Disorder Linked to Cerebellar Lesions.
AB  - Cerebellar dysfunction plays a critical role in neurodevelopmental disorders with
      long-term behavioral and neuropsychiatric symptoms. A 43-year-old woman with a
      cerebellum arteriovenous malformation and history of behavioral dysregulation
      since childhood is described. After the rupture of the cerebellar malformation in
      adulthood, her behavior morphed into specific psychiatric symptoms and cognitive
      deficits occurred. The neuropsychological assessment evidenced impaired
      performance in attention, visuospatial, memory, and language domains. Moreover,
      psychiatric assessment indicated a borderline personality disorder. Brain MRI
      examination detected macroscopic abnormalities in the cerebellar posterior
      lobules VI, VIIa (Crus I), and IX, and in the posterior area of the vermis,
      regions usually involved in cognitive and emotional processing. The described
      patient suffered from cognitive and behavioral symptoms that are part of the
      cerebellar cognitive affective syndrome. This case supports the hypothesis of a
      cerebellar role in personality disorders emphasizing the importance of also
      examining the cerebellum in the presence of behavioral disturbances in children
      and adults.

PMID- 29460205
TI  - Phylogeny and bioactivity of epiphytic Gram-positive bacteria isolated from three
      co-occurring antarctic macroalgae.
AB  - Marine macroalgae are emerging as an untapped source of novel microbial diversity
      and, therefore, of new bioactive secondary metabolites. This study was aimed at
      assessing the diversity and antimicrobial activity of the culturable Gram
      positive bacteria associated with the surface of three co-occurring Antarctic
      macroalgae. Specimens of Adenocystis utricularis (brown alga), Iridaea cordata
      (red alga) and Monostroma hariotii (green alga) were collected from the
      intertidal zone of King George Island, Antarctica. Gram-positive bacteria were
      investigated by cultivation-based methods and 16S rRNA gene sequencing, and
      screened for antimicrobial activity against a panel of pathogenic microorganisms.
      Isolates were found to belong to 12 families, with a dominance of
      Microbacteriaceae and Micrococcaceae. Seventeen genera of Actinobacteria and 2 of
      Firmicutes were cultured from the three macroalgae, containing 29 phylotypes.
      Three phylotypes within Actinobacteria were regarded as potentially novel
      species. Sixteen isolates belonging to the genera Agrococcus, Arthrobacter,
      Micrococcus, Pseudarthrobacter, Pseudonocardia, Sanguibacter, Staphylococcus,
      Streptomyces and Tessaracoccus exhibited antibiotic activity against at least one
      of the indicator strains. The bacterial phylotype composition was distinct among
      the three macroalgae species, suggesting that these macroalgae host species
      specific Gram-positive associates. The results highlight the importance of
      Antarctic macroalgae as a rich source of Gram-positive bacterial diversity and
      potentially novel species, and a reservoir of bacteria producing biologically
      active compounds with pharmacological potential.

PMID- 29460206
TI  - Deciphering the trophic interaction between Akkermansia muciniphila and the
      butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic
      approach.
AB  - Host glycans are paramount in regulating the symbiotic relationship between
      humans and their gut bacteria. The constant flux of host-secreted mucin at the
      mucosal layer creates a steady niche for bacterial colonization. Mucin
      degradation by keystone species subsequently shapes the microbial community. This
      study investigated the transcriptional response during mucin-driven trophic
      interaction between the specialised mucin-degrader Akkermansia muciniphila and a
      butyrogenic gut commensal Anaerostipes caccae. A. muciniphila monocultures and co
      cultures with non-mucolytic A. caccae from the Lachnospiraceae family were grown
      anaerobically in minimal media supplemented with mucin. We analysed for growth,
      metabolites (HPLC analysis), microbial composition (quantitative reverse
      transcription PCR), and transcriptional response (RNA-seq). Mucin degradation by
      A. muciniphila supported the growth of A. caccae and concomitant butyrate
      production predominantly via the acetyl-CoA pathway. Differential expression
      analysis (DESeq 2) showed the presence of A. caccae induced changes in the A.
      muciniphila transcriptional response with increased expression of mucin
      degradation genes and reduced expression of ribosomal genes. Two putative operons
      that encode for uncharacterised proteins and an efflux system, and several two
      component systems were also differentially regulated. This indicated A.
      muciniphila changed its transcriptional regulation in response to A. caccae. This
      study provides insight to understand the mucin-driven microbial ecology using
      metatranscriptomics. Our findings show that the expression of mucolytic enzymes
      by A. muciniphila increases upon the presence of a community member. This could
      indicate its role as a keystone species that supports the microbial community in
      the mucosal environment by increasing the availability of mucin sugars.

PMID- 29460208
TI  - A statistical approach to explore cemented total hip reconstruction performance.
AB  - This study was carried out to determine mechanical behavior and bone adaptation
      of total hip arthroplasty (THA) subject to concentrated and distributed muscle
      loads and hip contact forces during activities of walking and stair climbing.
      Finite element modeling of THA with different prostheses, activity and loading
      types was developed by adopting a statistical method. Two levels of prostheses,
      activity, and loading types were selected for the study. 23 factorial method was
      then pursued to design input and output data of finite element analysis. Maximum
      von Mises stresses were chosen to be output data on which statistical
      investigation was performed to investigate contribution and interaction of main
      factors on mechanical failure of cemented THA reconstructions by utilizing
      analysis of variance method (ANOVA). This study illustrated that the maximum von
      Mises stresses of THA showed considerable variation for main factors and their
      two-factor interactions.

PMID- 29460207
TI  - Bird feathers as potential sources of pathogenic microorganisms: a new look at
      old diseases.
AB  - This article describes methods of treatment for avian zoonoses, modern antibiotic
      therapy and drug resistance of selected pathogens, which pose a threat to the
      population's health. A tabular form has been used to present the current data
      from the European Union from 2011 to 2017 regarding human morbidity and mortality
      and the costs incurred by national health systems for the treatment of zoonoses
      occurring in humans and animals. Moreover, the paper includes descriptions of
      selected diseases, which indirectly affect birds. Scientists can obtain
      information regarding the occurrence of particular diseases, their aetiology,
      epidemiology, incubation period and symptoms caused by dangerous microorganisms
      and parasites. This information should be of particular interest for people who
      have frequent contact with birds, such as ornithologists, as well as
      veterinarians, farm staff, owners of accompanying animals and zoological workers.
      This paper presents a review used for identification and genetic characterization
      of bacterial strains isolated from a variety of environmental sources, e.g., bird
      feathers along with their practical application. We describe the bacterial, viral
      and fungal serotypes present on avian feathers after the slaughter process. This
      review also enables us to effectively identify several of the early stages of
      infectious diseases from heterogeneous avian research material.

PMID- 29460209
TI  - PCA-based selection of distinctive stability criteria and classification of post
      stroke pathological postural behaviour.
AB  - In this paper, we study the postural behaviour of two categories of people: Post
      CVA subjects suffering from cerebrovascular accident syndromes and healthy
      individuals under several levels of anterior-posterior and medial-lateral
      sinusoidal disturbances (0.1-0.5 Hz). These perturbations were produced from an
      omnidirectional platform called Isiskate. Afterwards, we have quantified seventy
      postural parameters, they were combined of linear stabilometric parameters and
      non-linear time dependent stochastic parameters using stabilogram diffusion
      analysis and some spectral attributes using power spectral density. The aim of
      our analysis is to reduce data dimensionality using principal component analysis
      (PCA). Furthermore, we proposed a new PCA-related criterion named: criterion of
      contribution in order to evaluate the contribution of every variable in the
      resulted system structure, and thus to eliminate the redundant postural
      characteristics. Afterwards, we highlighted some interesting distinctive
      parameters. The selected parameters were used thereafter in comparison between
      the studied groups. Finally, we created a classification model using support
      vector machines to distinguish stroke patients. Our proposed techniques help in
      understanding the human postural dynamics and facilitate the diagnosis of
      pathologies related to equilibrium which can be used to improve the
      rehabilitation services.

PMID- 29460210
TI  - Reply to Letter to the Editor: Giovanni Bibbo, Standardisation of shielding of
      medical X-ray installations.

PMID- 29460211
TI  - Validation of a Social Networks and Support Measurement Tool for Use in
      International Aging Research: The International Mobility in Aging Study.
AB  - The purpose of this study was to develop and validate a new instrument to assess
      social networks and social support (IMIAS-SNSS) for different types of social
      ties in an international sample of older adults. The study sample included n =
      1995 community dwelling older people aged between 65 and 74 years from the
      baseline of the longitudinal International Mobility in Aging Study (IMIAS). In
      order to measure social networks for each type of social tie, participants were
      asked about the number of contacts, the number of contacts they see at least once
      a month or have a very good relationship with, or speak with at least once a
      month. For social support, participants had to rate the level of social support
      provided by the four types of contacts for five Likert scale items. Confirmatory
      Factor Analysis was conducted to determine the goodness of fit of the measurement
      models. Satisfactory goodness-of-fit indices confirmed the satisfactory factorial
      structure of the IMIAS-SNSS instrument. Reliability coefficients were 0.80, 0.81,
      0.85, and 0.88 for friends, children, family, and partner models, respectively.
      The models were confirmed by CFA for each type of social tie. Moreover, IMIAS
      SNSS detected gender differences in the older adult populations of IMIAS. These
      results provide evidence supporting that IMIAS-SNSS is a psychometrically sound
      instrument and of its validity and reliability for international populations of
      older adults.

PMID- 29460212
TI  - Involvement of NF-kappaB in mediating the anti-tumour effects of combretastatins
      in T cells.
AB  - Purpose The combretastatins (CAs) are known to exhibit anti-tumour activity but
      the underlying mechanism remains to be fully elucidated. Inflammation plays a
      critical role in altering the function of cancer cells and evasion of cell death
      and increased proliferation are characteristics of transformed malignancies. Many
      of the proteins involved in these pathways are regulated by the transcription
      factor NF-kappaB which can be activated by tumour necrosis factor (TNF-alpha), a
      pro-inflammatory cytokine released by both malignant and immune cells within the
      tumour microenvironment. In this study, we examined the ability of combretastatin
      A-4 (CA-4) and its novel, cis-restricted analogue CA-432 to target the NF-kappaB
      signalling pathway in T cells. Methods Effects of the CAs on the viability of DND
      41 leukaemia and Jurkat lymphoma T-cell lines was assessed by the alamar blue
      assay. Induction of apoptosis and effects on expression levels of key apoptotic
      proteins was established though flow cytometry and western blotting. Modulation
      of the NF-kappaB signalling pathway was determined through western blotting and
      through assessment of NF-kappaB reporter gene activity. Results CA-4 and CA-432
      reduced cell viability and induced apoptosis in DND-41 and Jurkat T cells and
      sensitised the cells to TNF-alpha-induced apoptosis through inhibition of the NF
      kappaB signalling pathway. Suppression of the NF-kappaB pathway downregulated NF
      kappaB-dependent gene products involved in cell survival (IAPs, Bcl-2 and Mcl-1),
      proliferation (cyclin D1) and inflammation (COX-2). Furthermore, both CA-4 and CA
      432 inhibited TNF-alpha-induced NF-kappaB activation through the inhibition of
      IkappaBalpha degradation and p65 nuclear translocation and decreased NF-kappaB
      reporter gene activity. Conclusions Our data indicate that the anti-cancer
      properties of comebretastatins may be mediated in part through targeting the NF
      kappaB pathway. This study provides new insights into the molecular mechanisms of
      CA compounds and a potential application of combretastatins for inflammatory
      diseases such as cancers, which are associated with abnormal NF-kappaB
      activation.

PMID- 29460213
TI  - Evaluating the Probiotic Potential of Lactobacillus plantarum Strains from
      Algerian Infant Feces: Towards the Design of Probiotic Starter Cultures Tailored
      for Developing Countries.
AB  - Lactobacilli naturally present in the neonatal gut are believed to be beneficial
      for the human hosts and are investigated as potential probiotics. In this study,
      we aimed to characterize six Lactobacillus plantarum strains derived from the
      feces of a breast-fed infant, for the development of new probiotic cultures. Our
      attention was focused on L. plantarum in reason of the presence, within such
      species, of both pro-technological and probiotic strains, i.e., a combination of
      particular interest to design tailored probiotic starter cultures for developing
      countries. The bacterial isolates exhibiting lactobacilli-like phenotypic
      characteristics were identified as members of the L. plantarum group by 16S rRNA
      gene sequencing, and their diversity was evaluated by randomly amplified
      polymorphic DNA (RAPD) PCR patterns. The selected strains were screened for
      probiotic potential through in vitro tests. Firstly, bacterial survival was
      evaluated in an in vitro system simulating the human oro-gastrointestinal tract,
      using also milk as a carrier matrix. Besides, physiological traits such as
      antibiotic susceptibility, antimicrobial activity against selected enteric
      pathogens, and adhesion to abiotic surfaces and to gastric mucin were studied.
      Considering the resistance to simulated gastrointestinal digestion and the
      results from the biofilm and mucin adhesion tests, a strain-denominated L.
      plantarum LSC3 was selected for further evaluation of in vitro adhesion ability
      to intestinal mucosa and immunomodulatory activities. L. plantarum LSC3 was able
      to adhere efficiently to human enterocyte-like cells (Caco-2 cells), and
      decreased IL-8 transcription while increasing IL-10 mRNA level, as revealed by
      transcriptional analysis on LPS-stimulated human (THP-1) macrophages. Our results
      highlight that L. plantarum LSC3 fulfills major in vitro probiotic criteria as
      well as interesting immunostimulatory properties, and thus may be a promising
      candidate for further in vivo studies aiming at the development of novel
      probiotic starter cultures.

PMID- 29460214
TI  - Rational design and analysis of an Escherichia coli strain for high-efficiency
      tryptophan production.
AB  - L-tryptophan (L-trp) is a precursor of various bioactive components and has great
      pharmaceutical interest. However, due to the requirement of several precursors
      and complex regulation of the pathways involved, the development of an efficient
      L-trp production strain is challenging. In this study, Escherichia coli (E. coli)
      strain KW001 was designed to overexpress the L-trp operator sequences (trpEDCBA)
      and 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase (aroG fbr ). To further
      improve the production of L-trp, pyruvate kinase (pykF) and the
      phosphotransferase system HPr (ptsH) were deleted after inactivation of
      repression (trpR) and attenuation (attenuator) to produce strain KW006. To
      overcome the relatively slow growth and to increase the transport rate of
      glucose, strain KW018 was generated by combinatorial regulation of glucokinase
      (galP) and galactose permease (glk) expression. To reduce the production of
      acetic acid, strain KW023 was created by repressive regulation of phosphate
      acetyltransferase (pta) expression. In conclusion, strain KW023 efficiently
      produced 39.7 g/L of L-trp with a conversion rate of 16.7% and a productivity of
      1.6 g/L/h in a 5 L fed-batch fermentation system.

PMID- 29460215
TI  - Potential of biogenic methane for pilot-scale fermentation ex situ with lump
      anthracite and the changes of methanogenic consortia.
AB  - Pilot-scale fermentation is one of the important processes for achieving
      industrialization of biogenic coalbed methane (CBM), although the mechanism of
      biogenic CBM remains unknown. In this study, 16 samples of formation water from
      CBM production wells were collected and enriched for methane production, and the
      methane content was between 3.1 and 21.4%. The formation water of maximum methane
      production was used as inoculum source for pilot-scale fermentation. The maximum
      methane yield of the pilot-scale fermentation with lump anthracite amendment
      reached 13.66 MUmol CH4/mL, suggesting that indigenous microorganisms from
      formation water degraded coal to produce methane. Illumina high-throughput
      sequencing analysis revealed that the bacterial and archaeal communities in the
      formation water sample differed greatly from the methanogic water enrichment
      culture. The hydrogenotrophic methanogen Methanocalculus dominated the formation
      water. Acetoclastic methanogens, from the order Methanosarcinales, dominated coal
      bioconversion. Thus, the biogenic methanogenic pathway ex situ cannot be simply
      identified according to methanogenic archaea in the original inoculum.
      Importantly, this study was the first time to successfully simulate
      methanogenesis in large-capacity fermentors (160 L) with lump anthracite
      amendment, and the result was also a realistic case for methane generation in
      pilot-scale ex situ.

PMID- 29460216
TI  - Methodological Considerations in Couples' Fertility Intentions: Missing Men and
      the Viability of Women's Proxy Reports.
AB  - Introduction Recent efforts show potential to advance research on unintended
      childbearing by taking a couple-level approach. However, this work has neither
      adequately addressed methodological concerns stemming from the challenges
      associated with male fertility data nor considered the viability of women's proxy
      reports of fathers intentions. Methods Data from the Early Childhood Longitudinal
      Study, Birth Cohort (ECLS-B) were used to assess the implications of low response
      rates among men on couples' unintended childbearing. Then, the accuracy of
      women's proxy reports of fathers intentions was assessed. Weighted logistic
      regression analyses were conducted to determine how women's characteristics were
      associated with men's survey participation whereas weighted multinomial logistic
      regression analyses were applied to determine how women's characteristics were
      linked with the accuracy of her proxy report. Results Almost half (46%) of women
      cannot be matched with data from the child's father, and this discrepancy is most
      problematic for women who are black, foreign-born, less educated, and unmarried
      at birth. Women's proxy reports appear viable as 75% of women's reports are
      consistent with men's responses. Yet, proxy reports underestimate disagreement in
      couples' intentions as mothers who intended the birth are at an increased risk of
      "inaccurately" reporting that fathers share their intentions. Discussion Direct
      approaches to couples' intentions yield privileged samples and systematically
      omit women at the greatest risk of an unintended birth. However, proxies
      underestimate disagreement in couples' intentions-a key contribution to the
      couple approach. Accordingly each approach has its own merits which must be
      considered in light of specified research questions.

PMID- 29460217
TI  - Maternal Sociodemographic Characteristics, Experiences and Health Behaviors
      Associated with Postpartum Care Utilization: Evidence from Maryland PRAMS
      Dataset, 2012-2013.
AB  - Objectives Postpartum visits are increasingly recognized as a window of
      opportunity for health care providers to counsel new mothers and promote healthy
      behaviors, including increasing contraceptive use and screening for postpartum
      depression. In Maryland, there is a lack of research on postpartum visit (PPV)
      attendance and the specific risk factors associated with not receiving postpartum
      care. In this study, we estimated the proportion of mothers in Maryland who
      attended a PPV and assessed maternal sociodemographic characteristics and health
      behaviors associated with PPV non-attendance. Methods Data were analyzed from the
      2012 and 2013 Maryland Pregnancy Risk Assessment Monitoring System (n = 2204).
      Bivariate and multivariable logistic regression were performed to examine the
      association between covariates and PPV non-attendance. Results Overall, 89.6% of
      women reported PPV attendance. Bivariate analyses between maternal
      sociodemographic and health behavior characteristics and PPV non-attendance
      indicated that being unmarried (OR 3.03, 95% CI 2.12-4.31), experiencing infant
      loss (OR 7.17, 95% CI 2.57-19.97), working during pregnancy (OR 0.44, 95% CI 0.31
      0.63) and not receiving dental care (OR 2.03, 95% CI 1.43-2.88) as significant
      risk factors for PPV non-attendance. After controlling for known and theoretical
      confounders, experiencing an infant loss (aOR 5.18, 95% CI 1.54-17.4), not
      receiving dental care (aOR 1.54, 95% CI 1.06-2.26) and working during pregnancy
      (aOR 0.61, 95% CI 0.41-0.93) emerged as strong predictors of PPV non-attendance.
      Conclusions for Practice Mothers who recently experienced an infant death were at
      greatest risk for not attending a PPV, suggesting the need to establish
      comprehensive support networks, including grief counseling and additional service
      reminders for mothers who experienced an infant death.

PMID- 29460218
TI  - Hypoglycemia in type 2 diabetes: understanding patients' and physicians'
      knowledge and experience.
AB  - PURPOSE: The aim of the current study is to assess the patient and physician
      experience and knowledge of hypoglycemia in the management of type 2 diabetes
      (T2DM). METHODS: T2DM patients (N = 1002) completed questionnaires on
      hypoglycemia experience, familiarity, and fear. Their responses were compared
      across various antihyperglycemic treatment regimens; specifically, (1) insulin
      only or insulin combined with sulfonylurea [SU] and/or metformin, (2) SU only
      with/without metformin, and (3) neither insulin nor SU. Physicians (N = 1003)
      completed questionnaires on hypoglycemia knowledge and decision-making, and their
      responses were compared by specialty [75% primary care providers (PCPs) and 25%
      endocrinologists]. RESULTS: T2DM patients treated with, (1) insulin only, or (2)
      insulin plus SU or metformin, reported the most experience and familiarity with
      but also fear of-hypoglycemic events. Insulin-treated patients (insulin alone or
      insulin plus SU/metformin) also reported experiencing more hypoglycemia (all p
      values <0.012). For physicians, endocrinology specialty was significantly
      associated with higher hypoglycemia knowledge scores (all p-values <.001).
      Irrespective of specialty, physician hypoglycemia knowledge, in turn, was
      associated with correct treatment decision-making (all p-values <0.001).
      CONCLUSIONS: Insulin-based antihyperglycemic regimens were associated with high
      prevalence, severity, familiarity, and fear of hypoglycemia. An effective
      strategy to mitigate the burden of hypoglycemia may be to optimize
      pharmacological therapy to prevent these events. Since physician hypoglycemia
      knowledge was highly correlated to correct therapeutic decision-making, continued
      physician education regarding this acute complication of diabetes treatment
      should be prioritized for those managing patients with T2DM.

PMID- 29460220
TI  - Molecular identification of common Salmonella serovars using multiplex DNA sensor
      based suspension array.
AB  - Salmonella is one of major foodborne pathogens and the leading cause of foodborne
      illness-related hospitalizations and deaths. It is critical to develop a
      sensitive and rapid detection assay that can identify Salmonella to ensure food
      safety. In this study, a DNA sensor-based suspension array system of high
      multiplexing ability was developed to identify eight Salmonella serovars commonly
      associated with foodborne outbreaks to the serotype level. Each DNA sensor was
      prepared by activating pre-encoded microspheres with oligonucleotide probes that
      are targeting virulence genes and serovar-specific regions. The mixture of 12
      different types of DNA sensors were loaded into a 96-well microplate and used as
      a 12-plex DNA sensor array platform. DNA isolated from Salmonella was amplified
      by multiplex polymerase chain reaction (mPCR), and the presence of Salmonella was
      determined by reading fluorescent signals from hybridization between probes on
      DNA sensors and fluorescently labeled target DNA using the Bio-Plex(r) system.
      The developed multiplex array was able to detect synthetic DNA at the
      concentration as low as 100 fM and various Salmonella serovars as low as 100
      CFU/mL within 1 h post-PCR. Sensitivity of this assay was further improved to 1
      CFU/mL with 6-h enrichment. The array system also correctly and specifically
      identified serotype of tested Salmonella strains without any cross-reactivity
      with other common foodborne pathogens. Our results indicate the developed DNA
      sensor suspension array can be a rapid and reliable high-throughput method for
      simultaneous detection and molecular identification of common Salmonella
      serotypes.

PMID- 29460221
TI  - The genetics of aniridia - simple things become complicated.
AB  - Aniridia is a rare, panocular disorder characterized by a variable degree of
      hypoplasia or the absence of iris tissue associated with additional ocular
      abnormalities. It is inherited in an autosomal dominant manner, with high
      penetrance and variable expression even within the same family. In most cases the
      disease is caused by haploinsufficiency truncating mutations in the PAX6 gene;
      however, in up to 30% of aniridia patients, disease results from chromosomal
      rearrangements at the 11p13 region. The aim of this review is to present the
      clinical and genetic aspects of the disease. Furthermore, we present a molecular
      diagnostic strategy in the aniridia patients. Recent improvement in the genetic
      diagnostic approach will precisely diagnosis aniridia patients, which is
      essential especially for children with aniridia in order to determine the risk of
      developing a Wilms tumor or neurodevelopmental disorder. Finally, based on the
      previous studies we describe the current knowledge and latest research findings
      in the topic of pathogenesis of aniridia and possible future treatment.

PMID- 29460222
TI  - Heavy Metal Exposure and Metabolic Syndrome: Evidence from Human and Model System
      Studies.
AB  - PURPOSE OF REVIEW: Metabolic syndrome (MS) describes the co-occurrence of
      conditions that increase one's risk for heart disease and other disorders such as
      diabetes and stroke. The worldwide increase in the prevalence of MS cannot be
      fully explained by lifestyle factors such as sedentary behavior and caloric
      intake alone. Environmental exposures, such as heavy metals, have been
      implicated, but results are conflicting and possible mechanisms remain unclear.
      To assess recent progress in determining a possible role between heavy metal
      exposure and MS, we reviewed epidemiological and model system data for cadmium
      (Cd), lead (Pb), and mercury (Hg) from the last decade. RECENT FINDINGS: Data
      from 36 epidemiological studies involving 17 unique countries/regions and 13
      studies leveraging model systems are included in this review. Epidemiological and
      model system studies support a possible association between heavy metal exposure
      and MS or comorbid conditions; however, results remain conflicting.
      Epidemiological studies were predominantly cross-sectional and collectively, they
      highlight a global interest in this question and reveal evidence of differential
      susceptibility by sex and age to heavy metal exposures. In vivo studies in rats
      and mice and in vitro cell-based assays provide insights into potential
      mechanisms of action relevant to MS including altered regulation of lipid and
      glucose homeostasis, adipogenesis, and oxidative stress. Heavy metal exposure may
      contribute to MS or comorbid conditions; however, available data are conflicting.
      Causal inference remains challenging as epidemiological data are largely cross
      sectional; and variation in study design, including samples used for heavy metal
      measurements, age of subjects at which MS outcomes are measured; the scope and
      treatment of confounding factors; and the population demographics vary widely.
      Prospective studies, standardization or increased consistency across study
      designs and reporting, and consideration of molecular mechanisms informed by
      model system studies are needed to better assess potential causal links between
      heavy metal exposure and MS.

PMID- 29460223
TI  - PrEP Stigma: Implicit and Explicit Drivers of Disparity.
AB  - PURPOSE OF REVIEW: Despite its promise as an HIV prevention strategy, PrEP uptake
      remains slow, especially among highest priority populations. One factor that may
      be impeding implementation and driving disparities is PrEP-related stigma. This
      paper reviews the role of PrEP-related stigma in PrEP access, adherence, and
      persistence and examines its antecedents and consequences. RECENT FINDINGS:
      Although PrEP stigma is often experienced at the community level (i.e., by
      potential and current users), it can be reinforced and even amplified by public
      health programs, policy, and research. PrEP stigma disproportionately impacts
      disadvantaged groups and impedes scalability by influencing behavior of both
      patients and providers. Reducing PrEP stigma and its negative impact on the
      epidemic requires a significant shift in perspective, language, and programs.
      Such a shift is necessary to ensure broader reach of PrEP as a prevention
      strategy and improve its utilization by the individuals who need it most.

PMID- 29460224
TI  - Molecular Signatures of HIV-1 Envelope Associated with HIV-Associated
      Neurocognitive Disorders.
AB  - PURPOSE OF REVIEW: The HIV-1 envelope gene (env) has been an intense focus of
      investigation in the search for genetic determinants of viral entry and
      persistence in the central nervous system (CNS). RECENT FINDINGS: Molecular
      signatures of CNS-derived HIV-1 env reflect the immune characteristics and
      cellular constraints of the CNS compartment. Although more readily found in those
      with advanced HIV-1 and HIV-associated neurocognitive disorders (HAND), molecular
      signatures distinguishing CNS-derived quasispecies can be identified early in HIV
      1 infection, in the presence or absence of combination antiretroviral therapy
      (cART), and are dynamic. Amino acid signatures of CNS-compartmentalization and
      HAND have been identified across populations. While some significant overlap
      exists, none are universal. Detailed analyses of CNS-derived HIV-1 env have
      allowed researchers to identify a number of molecular determinants associated
      with neuroadaptation. Future investigations using comprehensive cohorts and
      longitudinal databases have the greatest potential for the identification of
      robust, validated signatures of HAND in the cART era.

PMID- 29460225
TI  - The Syndemic of Opioid Misuse, Overdose, HCV, and HIV: Structural-Level Causes
      and Interventions.
AB  - PURPOSE OF REVIEW: This article reviews the case for recognizing (1) the
      epidemics of opioid misuse, overdose, hepatitis C virus, and HIV as a syndemic
      and (2) the importance of examining and addressing structural factors in
      responses to this syndemic. We focus on the current syndemic in the US, but also
      consider data from other locations to highlight the issues existing and arising
      in various contexts. RECENT FINDINGS: Advances in multi-level theory and
      statistical methods allow sound ecologic and multi-level analyses of the impact
      of structural factors on the syndemic. Studies of opioid misuse, overdoses,
      hepatitis C virus, and HIV demonstrate that area-level access to healthcare,
      medication-assisted treatment of opioid use disorders, sterile injection
      equipment, and overdose prevention with naloxone, as well as factors such as
      opioid marketing, income inequality, intensity of policing activities, and health
      care policies, are related to the prevalence of substance misuse, overdoses,
      infection risk, and morbidity. Structural variables can predict area-level
      vulnerability to the syndemic. The implementation of combined prevention and
      treatment interventions can control and reverse components of the syndemic.
      Recognizing and monitoring potent structural factors can facilitate the
      identification of areas at risk of vulnerability to the syndemic. Further, many
      structural factors are modifiable through intervention and policy to reduce
      structural vulnerability and create health-enabling environments. Evidence
      supports the immediate implementation of broader HCV and HIV testing and
      substance use screening, medication-assisted treatment, needle/syringe exchange
      programs, naloxone programs, increased population-level implementation of HCV
      treatment, and further attention to structural-level factors predicting, and
      contributing to, area-level vulnerability, such as degrees of opioid marketing,
      distribution, and prescribing.

PMID- 29460226
TI  - Genetic Cluster Analysis for HIV Prevention.
AB  - PURPOSE OF REVIEW: This review summarizes the use of genetic similarity clusters
      to understand HIV transmission and inform prevention efforts. RECENT FINDINGS:
      Recent emphases include the development of real-time cluster identification in
      order to interrupt transmission chains, the use of clusters to estimate rates of
      transmission along the HIV care cascade, and the extension of cluster analyses to
      understand transmission in the generalized epidemics of sub-Saharan Africa.
      Importantly, this recent empirical work has been accompanied by theoretical work
      that elucidates the processes that underlie HIV genetic similarity clusters;
      multiple studies suggest that clusters are not necessarily enriched with
      individuals with high transmission rates, but rather can reflect variation in
      sampling times within a population, with individuals sampled early in infection
      more likely to cluster. Analyses of genetic similarity clusters have great
      promise to inform HIV epidemiology and prevention. Future emphases should include
      the collection of additional sequence data from underrepresented populations,
      such as those in sub-Saharan Africa, and further development and evaluation of
      clustering methods.

PMID- 29460227
TI  - Do frequent exposures to threats and violence at work affect later workforce
      participation?
AB  - PURPOSE: Threats and violence at work are common problems in the human service
      sector. It can result in physical and psychological health symptoms. The aim of
      this study was to examine the association between exposure to threats and
      violence and workforce participation in four human service sectors. METHODS: 5170
      employees answered questionnaires about threats and violence in 2010 and were
      followed in a register for public transfer incomes for 3.5 years to identify
      episodes of sick leave, general workforce participation, and permanent health
      related benefits. RESULTS: We found associations between exposures to threats and
      violence at work and workforce participation, though only a few specific types of
      threats and violence were associated on their own. Self-rated severity of both
      threatening and violent episodes was associated with overall low workforce
      participation, new sick leave episodes, and permanent health-related benefits.
      However, the latter was not statistically significant. The same pattern seems to
      be present in the relation between the total amount of exposure to threats and
      violence (threats score and violence score), respectively, and overall low
      workforce participation and new sick leave episodes. The threats score was also
      related to permanent health-related benefits. CONCLUSION: Exposure to threats and
      violence is associated with temporary and permanent health-related benefits as
      well as with low workforce participation in general, although some of the
      associations were not statistically significant.

PMID- 29460228
TI  - Prevalence of asymptomatic sexually transmitted infections in HIV-positive men
      who have sex with men in Germany: results of a multicentre cross-sectional study.
AB  - PURPOSE: Sexually transmitted infections (STIs) occur frequently in risk
      populations. Hereby, the role of screening-programmes remains controversial. Our
      study aimed to determine the prevalence of STI infections in HIV-positive men-who
      have-sex-with-men (MSM). METHODS: We enrolled asymptomatic, HIV-MSM in a
      prospective cross-sectional study from February to August 2016 at seven German
      HIV-centres. All subjects were screened for Treponema-pallidum (TP) and hepatitis
      B/C-infection. HIV RNA and screening for oral, rectal and urethral colonisation
      by Chlamydia-trachomatis (CT) and/or Neisseria-gonorrhoeae (NG) was performed.
      All subjects were asked to complete a sexual-risk-behaviour-questionnaire.
      RESULTS: In total, 296 subjects with a median age of 43.2 (36.2-49.5) years were
      enrolled; 99.3% were on ART for 5.5 (2.3-11.2) years. HIV RNA was < 50 copies/mL
      in 93.6%. Active syphilis infection was found in 5.0% of all patients, whereas
      55.4% had history of infection. HCV seropositivity was found in 33 patients
      (13.2%) and positive HCV RNA was available in 39.4%. 66/294 (22.5%) showed
      negative anti-HBs-antibodies, indicating lack of immunity. Overall, 40/296
      (13.5%) had positive CT/NG swabs (CT in 8.8%; 7.3% anorectal, 1.7% oropharyngeal,
      1.0% urethral and NG in 6.8%; 4.5% anal, 2.0% oropharyngeal, 1.4% urethral). Time
      since HIV infection < 7 years (OR 2.6 (1.2-5.5); p = 0.012), the use of
      inhalative nitrites ("poppers") (OR 2.8 (1.3-5.9; p = 0.008) and reporting
      unprotected intercourse with > 20 partners within the last 6 months [OR 3.0 (1.2
      7.8); p = 0.003] were significantly associated in multivariate analysis.
      CONCLUSION: We found high numbers of asymptomatic syphilis, hepatitis-C and CT/NG
      infections in HIV-MSM, remarkably in patients with shorter duration of HIV
      infection with more sexual partners within last 6 months.

PMID- 29460230
TI  - Flexible 3D carbon nanotubes cuff electrodes as a peripheral nerve interface.
AB  - The cuff electrode provides a stable interface with peripheral nerves, which has
      been widely used in basic research and clinical practice. Currently, the cuff
      electrodes are limited by the planar processing of microfabrication. This paper
      presents a novel cuff electrode using high-aspect ratio carbon nanotubes (CNTs)
      integrated on a flexible biocompatible parylene. The microfabrication process
      unites the high quality vertical CNTs grown at high temperature with the heat
      sensitive parylene substrate in a highly controllable manner. The fabricated cuff
      electrodes have been utilized for extracellular nerve stimulation in rats. The
      experimental results demonstrate the proposed CNT electrode has a better
      performance than Pt electrode in nerve stimulation. Moreover, the effect of
      electrode position and stimulation frequency is demonstrated in this paper. This
      preliminary data indicates that flexible 3D CNTs cuff electrode provides an
      excellent platform for functional electrical stimulation.

PMID- 29460229
TI  - Ceftolozane-tazobactam therapy for multidrug-resistant Pseudomonas aeruginosa
      infections in patients with hematologic malignancies and hematopoietic-cell
      transplant recipients.
AB  - Multidrug-resistant (MDR) Pseudomonas aeruginosa infection causes significant
      mortality among patients with hematologic malignancies and hematopoietic-cell
      transplant recipients. Ceftolozane-tazobactam (C-T) is a novel therapeutic option
      for MDR-P. aeruginosa infections but clinical experience in these patients is
      limited. We report favorable clinical outcomes and lack of limiting toxicities
      using C-T monotherapy to treat invasive MDR-P. aeruginosa infections in these
      patient populations.

PMID- 29460231
TI  - A biocompatible sol-gel derived titania coating for medical implants with
      antibacterial modification by copper integration.
AB  - Implant-associated infections are dangerous complications and may cause dramatic
      illness with hematogeneous spread of bacteria and secondary infections. Since
      treatment of these infections remains most challenging and commonly requires
      implant removal, prevention is of utmost importance. In the present work a
      titania-sol was equipped with a copper salt resulting after calcination in a
      titania coating (TiO2) with antibacterial properties combined with good
      cytocompatibility. In vitro tests with bacteria as well as tissue cells were
      carried out under corresponding conditions. Mouse fibroblasts and different
      staphylococcal strains were used for growth inhibition assays with serial
      dilutions of CuCl2. Cultivation on the surface of bare Ti6Al4V, TiO2-coated and
      copper-filled TiO2-coated Ti6Al4V samples was performed with both bacteria and
      tissue cells. Bacterial and cellular proliferation and mitochondrial activity
      were hereby determined. Coating of Ti6Al4V with pure TiO2 significantly improved
      cytocompatibility compared to the uncoated alloy. In the growth inhibition
      assays, fibroblasts tolerated higher concentrations of copper ions than did
      bacteria. Nevertheless, copper integration reduced fibroblast proliferation and
      mitochondrial activity on the surface coating. On the other hand, integration of
      copper into the TiO2-coating significantly reduced adhesion of viable bacteria
      resulting in a promising combination of cytocompatibility and antibacterial
      properties. Additionally, significant bacterial growth inhibition by
      antibacterial amounts of copper was also demonstrated in the supernatant. In
      conclusion, the copper-loaded TiO2-coatings for medical implants may be a
      promising approach to reduce the rate of implant-associated infections.

PMID- 29460232
TI  - Atrial fibrillation ablation using very short duration 50 W ablations and contact
      force sensing catheters.
AB  - PURPOSE: The optimal radiofrequency (RF) power and lesion duration using contact
      force (CF) sensing catheters for atrial fibrillation (AF) ablation are unknown.
      We evaluate 50 W RF power for very short durations using CF sensing catheters
      during AF ablation. METHODS: We evaluated 51 patients with paroxysmal (n = 20) or
      persistent (n = 31) AF undergoing initial RF ablation. RESULTS: A total of 3961
      50 W RF lesions were given (average 77.6 +/- 19.1/patient) for an average
      duration of only 11.2 +/- 3.7 s. As CF increased from < 10 to > 40 g, the RF
      application duration decreased from 13.7 +/- 4.4 to 8.6 +/- 2.5 s (p < 0.0005).
      Impedance drops occurred in all ablations, and for patients in sinus rhythm,
      there was loss of pacing capture during RF delivery suggesting lesion creation.
      Only 3% of the ablation lesions were at < 5 g and 1% at > 40 g of force. As CF
      increased, the force time integral (FTI) increased from 47 +/- 24 to 376 +/- 102
      gs (p < 0.0005) and the lesion index (LSI) increased from 4.10 +/- 0.51 to 7.63
      +/- 0.50 (p < 0.0005). Both procedure time (101 +/- 19.7 min) and total RF energy
      time (895 +/- 258 s) were very short. For paroxysmal AF, the single procedure
      freedom from AF was 86% at 1 and 2 years. For persistent AF, it was 83% at 1 year
      and 72% at 2 years. There were no complications. CONCLUSIONS: Short duration 50 W
      ablations using CF sensing catheters are safe and result in excellent long-term
      freedom from AF for both paroxysmal and persistent AF with short procedure times
      and small amounts of total RF energy delivery.

PMID- 29460233
TI  - Late cure of focal ventricular arrhythmias post-catheter ablation:
      electrophysiological characteristics and long-term outcome.
AB  - PURPOSE: Late cure after a previously failed ablation of ventricular arrhythmias
      (VAs) is a relatively common phenomenon. The present study sought to delineate
      the incidence and electrophysiological characteristics of late cure in idiopathic
      VA patients. METHODS: Totally, 45 idiopathic VA cases (mean age 44 +/- 18 years,
      27 males) either failed acutely or recurred within 12 h were enrolled in this
      study. Based on intensive clinical observations in the acute period, 19 (42%)
      patients demonstrated late cure in the first week after the procedure. RESULTS:
      The late cure patients had significantly better acute and cumulative ablation
      effects during the procedure than did those without a late cure. Additionally,
      they had a prediction that originated from the right ventricular outflow tract,
      aortic-mitral continuum, and left summit area relative to other sites (13/18 vs
      6/27, p < 0.01). In a median follow-up of 24 [14, 46] months, 7/19 (37%) patients
      had their VAs recurred. The late cure group had significantly more patients cured
      at long-term follow-up than those without (12/19 vs 0/26, p < 0.01). A cutoff
      value of the "time to eliminate VAs" > 7.0 s was able to predict a long-term
      recurrence of the VAs with 62.5% sensitivity and 85.7% specificity. CONCLUSIONS:
      The late cure of VAs occurs in more than one third of patients who have a
      seemingly unsuccessful ablation session, which is clustered in the first week
      after the procedure. However, long-term recurrence of VAs occurred in 37% of the
      late cure patients, emphasizing the importance of long-term follow-up.

PMID- 29460234
TI  - Implementation of a near-zero fluoroscopy approach in interventional
      electrophysiology: impact of operator experience.
AB  - PURPOSE: Catheter ablation is performed under fluoroscopic guidance. Reduction of
      radiation dose for patients and staff is emphasized by current recommendations.
      Previous studies have shown that lower operator experience leads to increased
      radiation dose. On the other hand, less experienced operators may depend even
      more on fluoroscopic guidance. Our study aimed to evaluate feasibility and
      efficacy of a non-fluoroscopic approach in different training levels. METHODS:
      From January 2017, a near-zero fluoroscopy approach was established in two
      centers. Four operators (beginner, 1st year fellow, 2nd year fellow, expert) were
      instructed to perform the complete procedure with the use of a 3-D mapping system
      without fluoroscopy. A historical cohort that underwent procedures with
      fluoroscopy use served as control group. Dose area product (DPA), procedure
      duration, acute procedural success, and complications were compared between the
      groups and for each operator. RESULTS: Procedures were performed in 157 patients.
      The first 100 patients underwent procedures with fluoroscopic guidance, the
      following 57 procedures were performed with the near-zero fluoroscopy approach.
      The results show a significant reduction in DPA for all operators immediately
      after implementation of the near-zero fluoroscopy protocol (control 637 +/- 611
      MUGy/m2; beginner 44.1 +/- 79.5 MUGy/m2, p = 0.002; 1st year fellow 24.3 +/-
      46.4.5 MUGy/m2, p = 0.001; 2nd year fellow 130.3 +/- 233.3 MUGy/m2, p = 0.003;
      expert 9.3 +/- 37.4 MUGy/m2, P < 0.001). Procedure duration, acute success, and
      complications were not significantly different between the groups. CONCLUSION:
      Our results show a 90% reduction of DPA shortly after implementation of a near
      zero fluoroscopy approach in interventional electrophysiology even in operators
      in training.

PMID- 29460235
TI  - Response and outcomes of cardiac resynchronization therapy in patients with renal
      dysfunction.
AB  - PURPOSE: Renal dysfunction is often associated with chronic heart failure,
      leading to increased morbi-mortality. However, data regarding these patients
      after cardiac resynchronization therapy (CRT) is sparse. We sought to evaluate
      response and long-term mortality in patients with heart failure and renal
      dysfunction and assess renal improvement after CRT. METHODS: We analyzed 178
      consecutive patients who underwent successful CRT device implantation (age 64 +/-
      11 years; 69% male; 92% in New York Heart Association (NYHA) functional class >=
      III; 34% with ischemic cardiomyopathy). Echocardiographic response was defined as
      >= 15% reduction in left ventricular end-systolic diameter and clinical response
      as a sustained improvement of at least one NYHA functional class. Renal
      dysfunction was defined as an estimated glomerular filtration rate (eGFR) below
      60 mL/min/1.73 m2. RESULTS: Renal dysfunction was present in 34.7%. Renal
      dysfunction was not an independent predictor of echocardiographic response (OR
      1.109, 95% CI 0.713-1.725, p 0.646) nor clinical response (OR 1.003; 95% CI 0.997
      1.010; p 0.324). During follow-up (mean 55.2 +/- 32 months), patients with eGFR <
      60mL/min/1.73 m2 had higher overall mortality (HR 4.902, 95% CI 1.118-21.482, p
      0.035). However, clinical response in patients with renal dysfunction was
      independently associated with better long-term survival (HR 0.236, 95% CI 0.073
      0.767, p 0.016). Renal function was significantly improved in patients who
      respond to CRT (DeltaeGFR + 5.5 mL/min/1.73 m2 at baseline vs. follow-up, p
      0.049), while this was not evident in nonresponders. Improvements in eGFR of at
      least 10 mL/min/1.73 m2 were associated with improved survival in renal
      dysfunction patients (log-rank p 0.036). CONCLUSION: Renal dysfunction was
      associated with higher long-term mortality in CRT patients, though, it did not
      influence echocardiographic nor functional response. Despite worse overall
      prognosis, renal dysfunction patients who are responders showed long-term
      survival benefit and improvement in renal function following CRT.

PMID- 29460236
TI  - A double-blind, randomised, placebo-controlled, cross-over study assessing the
      use of XEN-D0103 in patients with paroxysmal atrial fibrillation and implanted
      pacemakers allowing continuous beat-to-beat monitoring of drug efficacy.
AB  - PURPOSE: The ultrarapid delayed rectifier current (IKur) carried by Kv1.5
      channels, which are solely expressed in the atrium, is a potential target for
      safer treatment of paroxysmal atrial fibrillation (PAF). XEN-D0103 is a nanomolar
      ion channel blocker that selectively inhibits potassium ion flux through the
      Kv1.5 ion channel. The efficacy of XEN-D0103 in reducing AF burden was assessed
      in patients with DDDRp permanent pacemakers (PPMs) and PAF. METHODS: A double
      blind, placebo-controlled, cross-over study was performed in patients with PAF
      and DDDRp PPMs with advanced atrial and ventricular Holters allowing beat-to-beat
      arrhythmia follow-up. All anti-arrhythmic drugs were withdrawn before randomised
      treatment. After baseline assessment, patients were randomly assigned to two
      treatment periods of placebo then XEN-D0103 50 mg bd, or XEN-D0103 50 mg bd then
      placebo. RESULTS: Fifty-four patients were screened and 21 patients were eligible
      and included in the randomised trial. All 21 patients completed both treatment
      periods. The primary endpoint was change in AF burden assessed by PPM. There was
      no significant difference in AF burden on treatment with XEN-D0103 versus
      placebo. There was a reduction in the mean frequency of AF episodes (relative
      reduction 0.72, 95% CI 0.66 to 0.77; p < 0.0001). XEN-D0103 was safe and well
      tolerated, and there were no serious adverse events. XEN-D0103 did not have any
      apparent effect on heart rate compared to placebo. CONCLUSIONS: XEN-D0103 did not
      reduce AF burden in patients with PAF and dual chamber pacemakers providing beat
      to-beat monitoring. XEN-D0103 was well tolerated and did not have any apparent
      effect on heart rate. Although single-ion channel blockade with XEN-D0103 did not
      affect AF in this study, there might be a potential for this agent to be used in
      combination with other atrially specific drugs in the treatment of AF. EUDRACT
      TRIAL REGISTRATION NUMBER: 2013-004456-38.

PMID- 29460237
TI  - A Comparison of the Impacts of Wind Energy and Unconventional Gas Development on
      Land-use and Ecosystem Services: An Example from the Anadarko Basin of Oklahoma,
      USA.
AB  - The United States energy industry is transforming with the rapid development of
      alternative energy sources and technological advancements in fossil fuels. Two
      major changes include the growth of wind turbines and unconventional oil and gas.
      We measured land-use impacts and associated ecosystem services costs of
      unconventional gas and wind energy development within the Anadarko Basin of the
      Oklahoma Woodford Shale, an area that has experienced large increases in both
      energy sectors. Unconventional gas wells developed three times as much land
      compared to wind turbines (on a per unit basis), resulting in higher ecosystem
      services costs for gas. Gas wells had higher impacts on intensive agricultural
      lands (i.e., row crops) compared to wind turbines that had higher impacts on
      natural grasslands/pastures. Because wind turbines produced on average less
      energy compared to gas wells, the average land-use-related ecosystem cost per
      gigajoule of energy produced was almost the same. Our results demonstrate that
      both unconventional gas and wind energy have substantial impacts on land use,
      which likely affect wildlife populations and land-use-related ecosystem services.
      Although wind energy does not have the associated greenhouse gas emissions, we
      suggest that the direct impacts on ecosystems in terms of land use are similar to
      unconventional fossil fuels. Considering the expected rapid global expansion of
      these two forms of energy production, many ecosystems are likely to be at risk.

PMID- 29460238
TI  - Forward-looking farmers owning multiple potential wetland restoration sites:
      implications for efficient restoration.
AB  - Wetland restoration can increase the provision of multiple non-market ecosystem
      services. Environmental and socio-economic factors need to be accounted for when
      land is withdrawn from agriculture and wetlands are restored. We build multi
      objective optimization models to provide decision support for wetland restoration
      in the Le Sueur river watershed in Southern Minnesota. We integrate environmental
      objectives of sediment reduction and habitat protection with socio-economic
      factors associated with the overlap of private land with potential wetland
      restoration sites in the watershed and the costs representing forward-looking
      farmers voluntarily taking land out of agricultural production in favor of
      wetland restoration. Our results demonstrate that the inclusion of these factors
      early on in the restoration planning process affects both the total costs of the
      restoration project and the spatial distribution of optimally selected wetland
      restoration sites.

PMID- 29460239
TI  - Clinical and pathophysiological aspects of type 1 autoimmune pancreatitis.
AB  - In 1995, Yoshida and colleagues proposed the concept of "autoimmune pancreatitis"
      (AIP), which has recently been recognized as a new pancreatic inflammatory
      disease. Recent studies have suggested the existence of two subtypes of AIP: type
      1, which involves immunoglobulin G4 (IgG4) and is the pancreatic manifestation of
      IgG4-related disease (IgG4-RD); and type 2, which is characterized by
      granulocytic epithelial lesions. Type 2 AIP is thought to be rare in Japan. Type
      1 AIP is characterized by increased serum IgG4 concentrations, lymphoplasmacytic
      infiltrations, storiform fibrosis, and obliterative phlebitis. However, although
      type 1 AIP has become increasingly recognized, many clinical and basic issues
      remain to be solved. This review provides an overview of the recent clinical and
      basic knowledge of type 1 AIP.

PMID- 29460240
TI  - Correction to: Removal of fluoroquinolone from aqueous solution using graphene
      oxide: experimental and computational elucidation.
AB  - Unfortunately, the original version of this article contains a mistake. The
      figures no. 10, 11, 12 and 13 in the original version of the article should be
      replaced by the figures shown in this paper.

PMID- 29460242
TI  - Revisiting energy intensity convergence: new evidence from OECD countries.
AB  - In this study, we examine the energy intensity convergence in OECD countries
      within the context of recent developments in unit root analysis by paying
      attention to modeling structural shifts. We collect the total primary energy
      consumption/GDP data of 27 OECD countries during the period 1980-2014. The
      findings indicate that controlling for shifts plays a crucial role, and different
      approximations in modeling breaks lead to changes in inferences. In conclusion,
      we present some policy proposals.

PMID- 29460241
TI  - Ecological and human health risks arising from exposure to metals in urban soils
      under different land use in Nigeria.
AB  - The concentrations of eight metals (Cd, Pb, Cr, Ni, Cu, Mn, Zn and Fe) were
      measured in soils under different land use in an urban environment of the Niger
      Delta in Nigeria. The aim was to provide information on the potential ecological
      and human health risks associated with human exposure to metals in these soils.
      The potential ecological risk due to metals in soils of these land use types
      falls in the range of low to moderate ecological risk with a significant
      contribution from Cd. The severity of the individual metals to ecological risk in
      these land use types followed the order Cd > Pb > Zn > Cu > Ni > Cr > Mn. The non
      carcinogenic risk, expressed in terms of the hazard index (HI), arising through
      exposure to metals through oral, dermal and inhalation pathways, was greater than
      1 for children in the majority of the land use types and less than 1 for adults
      for all land use types. This indicated that there are considerable non-cancer
      risks arising from childhood exposure to metals in soils of these land use types.
      The cancer risk values were within acceptable threshold values indicating a
      negligible cancer risk for both children and adults exposed to metals in these
      urban soils.

PMID- 29460243
TI  - Effect of spent mushroom substrate as a bulking agent on gaseous emissions and
      compost quality during pig manure composting.
AB  - The aim of this study was to investigate the gaseous emissions (CH4, N2O, and
      NH3) and compost quality during the pig manure composting by adding spent
      mushroom substrate (SMS) as a bulking agent. The control treatment was also
      studied using corn stalk (CS) as a bulking agent. The experiment was conducted in
      a pilot scale composting reactor under aerobic condition with the initial C/N
      ratio of 20. Results showed that bulking agents significantly affected gaseous
      emissions and compost quality. Using SMS as a bulking agent improved composting
      efficiency by shortening the time for maturity. SMS increased germination index
      and humic acid of the final compost (by 13.44 and 41.94%, respectively) compared
      with CS. Furthermore, composting with SMS as a bulking agent could reduce
      nitrogen loss, NH3, and N2O emissions (by 13.57, 35.56, and 46.48%, respectively)
      compared with the control. SMS slightly increased CH4 emission about 1.1 times of
      the CS. However, a 33.95% decrease in the global warming potential of CH4 and N2O
      was obtained by adding SMS treatment. These results indicate that SMS is a
      favorable bulking agent for reducing gaseous emissions and increasing compost
      quality.

PMID- 29460244
TI  - Rhizospheric effects on atrazine speciation and degradation in laterite soils of
      Pennisetum alopecuroides (L.) Spreng.
AB  - Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) is a worldwide
      used herbicide and often detected in agricultural soils and groundwater at
      concentrations above the permitted limit, because of its high mobility,
      persistence, and massive application. This study applied pot experiments to
      investigate the atrazine contents and speciation during the phytoremediation
      process by Pennisetum alopecuroides (L.) Spreng. in laterite soils. From the
      change of the total atrazine and bioavailable atrazine measured by diffusive
      gradients in thin film (DGT), P. alopecuroides significantly improved atrazine
      degradation efficiency from 15.22 to 51.46%, attributing to the increasing
      bioavailable atrazine in rhizosphere. Only a small amount of atrazine was taken
      up by P. alopecuroides root and the acropetal translocation from roots to shoots
      was limited. The atrazine speciation was significantly different between
      rhizosphere and non-rhizosphere, attributing to the declining pH and organic
      matters in rhizosphere. The relationship between pH and soil-bound/humus-fixed
      atrazine illustrated the pH-dependant release of the atrazine from soils and the
      competition between humus adsorption and uptake by P. alopecuroides. The present
      study reveals the important roles of soil pH and organic matters in atrazine
      speciation and availability in laterite soils, and provides new insights in the
      rhizospheric effects on effective phytoremediation of atrazine.

PMID- 29460245
TI  - Larvicidal activity of selected plant extracts and their combination against the
      mosquito vectors Culex quinquefasciatus and Aedes aegypti.
AB  - In order to develop an environment-friendly botanical mosquito larvicide
      alternative to the chemical larvicides, extracts were made from the leaves of
      Hyptis suaveolens, Lantana camara, Nerium oleander, and Tecoma stans with three
      organic solvents such as methanol (ME), chloroform (CH), and petroleum ether (PE)
      using a Soxhlet extractor. The plant extracts were screened for larvicidal
      activity individually and in combination against the larvae of Aedes aegypti and
      Culex quinquefasciatus as per WHO protocol. Among the extracts, the maximum
      larvicidal activity was shown by the PE extract of L. camara (LC50 10.63 mg/L)
      followed by the PE extract of T. stans (LC50 19.26 mg/L), ME extract of N.
      oleander (LC50 35.82 mg/L), and PE extract of H. suaveolens (LC50 38.39 mg/L)
      against Cx. quinquefasciatus. In the case of Ae. aegypti, the PE extract of T.
      stans showed maximum activity with LC50 value of 55.41 mg/L followed by H.
      suaveolens (LC50 64.49 mg/L), PE extract of L. camara (LC50 74.93 mg/L), and ME
      extract of N. oleander (LC50 84.09). A blend of these four extracts resulted in a
      combination with corresponding LC50 values of 4.32 and 7.19 mg/L against Cx.
      quinquefasciatus and Ae. aegypti. The predator safety factors were 12.55 and
      20.88 for Gambusia affinis with respect to Aedes and Culex larvae for the extract
      combination. Chemical constituents in extracts were also identified by FT-IR and
      GC-MS data. The present investigations suggest the possible use of this blend of
      botanical extracts as an ideal ecofriendly, larvicide against Ae. aegypti and Cx.
      quinquefasciatus larvae.

PMID- 29460246
TI  - Fluorescence quenching of MoS2 nanosheets/DNA/silicon dot nanoassembly: effective
      and rapid detection of Hg2+ ions in aqueous solution.
AB  - Mercury (Hg) contamination of aquatic sites represents a serious risk for human
      health and the environment. Therefore, effective and rapid monitoring of Hg in
      aqueous samples is a challenge of timely importance nowadays. In the present
      study, a rapid and sensitive mercury sensor based on the fluorescence quenching
      of MoS2 nanosheets/DNA/silicon dot nanoassembly has been developed for the
      efficient detection of mercury(II) in aquatic environments. In this process,
      silicon dots were synthesized through one-step high-temperature calcinations and
      thermomagnesium reduction method at 900  degrees C using rice husk as a silicon
      source, which demonstrates superior photophysical properties and excitation
      dependent fluorescence behavior. The interaction between MoS2
      nanosheets/DNA/silicon dot nanoassembly and Hg2+ ions was studied using
      photoluminescence spectroscopy. The addition of Hg2+ ions to the assay solution
      induced the detachment of fluorescent probe from the surface of MoS2 nanosheets.
      Thus, the fluorescent probes sustained its fluorescence intensity. The developed
      sensor was tested on various concentrations of Hg2+ ions ranging from 0 to 1000
      nM as well as on various metal ions. In addition, MoS2 nanosheets/DNA/silicon dot
      nanoassembly fluorescent Hg sensor efficiently detected the presence of Hg2+ ions
      in real-time water samples, which was comparably detected by the conventional
      atomic absorbance spectrometer (AAS). Overall, our results highlighted the high
      reliability of the present approach for environmental monitoring of Hg2+ ions, if
      compared to that of the customary method with a lowest detection limit of 0.86
      nM.

PMID- 29460247
TI  - Role of soil physicochemical properties in quantifying the fate of diuron,
      hexazinone, and metribuzin.
AB  - The physicochemical properties of soil are fundamental to quantification of the
      fate of herbicides. Thus, the aim of this research was to evaluate the fate of
      diuron, hexazinone, and metribuzin in five soils (Clay-1, Clay-2, Loam-1, Loam-2,
      and Sand), presenting variation in clay content, cation exchange capacity (CEC),
      pH, and organic carbon (OC). Herbicides radiolabeled with 14C were applied, and
      the 14C-CO2 released from mineralization was trapped in 0.2 mol L-1 sodium
      hydroxide solution. The degradation ratio, as well as herbicide-bound residues
      (non-extractable), transformation products, and residues extractable from soil,
      was also evaluated. Average 14C-CO2 evolution accumulated for diuron
      mineralization was higher (22.24%) than hexazinone (7.73%) and metribuzin
      (3.20%). The degradation time half-life (DT50) values for hexazinone correlated
      with soil OC content. Although no correlation between soil properties and DT50
      values was found for metribuzin, the degradation rate and total degree of
      mineralization were low in sand soil for metribuzin. Regarding diuron, OC content
      and CEC value appear to be related to mineralization and degradation rate,
      respectively. Differences in soil properties can influence the persistence and
      fate of herbicides, affecting their impact on the environment, weed control, and
      possible effects on subsequent crops.

PMID- 29460248
TI  - Mediative mechanism of bicarbonate on anaerobic propionate degradation revealed
      by microbial community and thermodynamics.
AB  - Syntrophic acetogenesis of volatile fatty acids (VFAs) such as propionate and
      butyrate is considered as the rate-limiting step of anaerobic digestion. Though
      being extensively researched, the mechanism is not well understood as the main
      constraint on developing effective solutions to the practical problem. In the
      present research work, the mediation of methanogenic propionate degradation by
      exogenous bicarbonate was evaluated, while the mechanism was revealed by
      microbial community and thermodynamics. It was found that the exogenous
      bicarbonate not more than 0.10 mol/L acted as a mediative role to enrich
      syntrophic acetogenic bacteria and decrease the actual Gibbs free energy change
      (DeltaG) of syntrophic acetogenesis reaction, resulted in the increased
      degradation rate and methane production rate of propionate. The remarkably
      increased DeltaG of methanogenic propionate degradation by the exogenous
      bicarbonate more than 0.15 mol/L decreased the degradation rate and methane
      production rate of propionate, though the DeltaG of syntrophic acetogenesis
      reaction was also decreased by the exogenous bicarbonate. This research work
      provided a control strategy to enhance syntrophic acetogenesis, as well as the
      methanogenic VFAs degradation.

PMID- 29460250
TI  - Metals in Racomitrium lanuginosum from Arctic (SW Spitsbergen, Svalbard
      archipelago) and alpine (Karkonosze, SW Poland) tundra.
AB  - Arctic-alpine tundra habitats are very vulnerable to the input of relatively
      small amounts of xenobiotics, and thus their level in such areas must be
      carefully controlled. Therefore, we collected the terrestrial widespread moss
      Racomitrium lanuginosum (Hedw.) Brid. in Spitsbergen in the Arctic moss lichen
      tundra and, for comparison, in the Arctic-alpine tundra in the Karkonosze (SW
      Poland). Concentrations of the elements Cd, Co, Cr, Cu, Fe, Hg, Li, Mn, Mo, Na,
      Ni, Pb, V, and Zn in this species and in the parent rock material were measured.
      We tested the following hypothesis: R. lanuginosum from Spitsbergen contains
      lower metal levels than the species from the Karkonosze collected at altitudes
      influenced by long-range transport from former Black Triangle industry. Principal
      component and classification analysis (PCCA) ordination revealed that mosses of
      Spitsbergen were distinguished by a significantly higher Na concentration of
      marine spray origin and mosses of Karkonosze were distinguished by significantly
      higher concentrations of Cd, Cr, Cu, Fe, Hg, Li, Mn, Pb, V, and Zn probably from
      long-range atmospheric transport. The influence of the polar station with a waste
      incinerator resulted in significantly higher Co, Li, and Ni concentrations in
      neighbouring mosses in comparison with this species from other sites. This
      investigation contributes to the use of R. lanuginosum as a bioindicator for
      metal contamination in Arctic and alpine tundra regions characterised by severe
      climate habitats with a restricted number of species. This moss enables the
      control of pollution usually brought solely by long-range atmospheric transport
      in high mountains as well as in Arctic areas.

PMID- 29460249
TI  - Improving photoelectrochemical reduction of Cr(VI) ions by building alpha
      Fe2O3/TiO2 electrode.
AB  - Photoelectrochemical process is an environmentally friendly technology and has a
      wide application in the control of environmental pollutants. Efficient
      nanophotocatalysts responsive to visible light are still highly attractive. In
      this work, alpha-Fe2O3/TiO2 were grown on fluorine doped tin oxide (FTO)
      substrates by hydrothermal method for photoelectrochemical reduction of Cr(VI).
      Compared with the separate alpha-Fe2O3 and TiO2 electrodes, the composite alpha
      Fe2O3/TiO2 electrodes show higher photocurrent density. Under visible light
      irradiation, 100% removal efficiency of Cr(VI) was obtained after 40 min
      treatment. The composite alpha-Fe2O3/TiO2 electrodes showed an enhanced
      absorbance in visible light region and had good stability to photoelectrochemical
      reduction of Cr(VI). The role of hole scavengers (citric acid and oxalic acid)
      and pH values was systematically investigated. This novel intensification
      approach provides new insight on the application of photoelectrochemical
      reduction in environmental remediation.

PMID- 29460251
TI  - Comparison of emerging contaminants in receiving waters downstream of a
      conventional wastewater treatment plant and a forest-water reuse system.
AB  - Forest-water reuse (FWR) systems treat municipal, industrial, and agricultural
      wastewaters via land application to forest soils. Previous studies have shown
      that both large-scale conventional wastewater treatment plants (WWTPs) and FWR
      systems do not completely remove many contaminants of emerging concern (CECs)
      before release of treated wastewater. To better characterize CECs and potential
      for increased implementation of FWR systems, FWR systems need to be directly
      compared to conventional WWTPs. In this study, both a quantitative, targeted
      analysis and a nontargeted analysis were utilized to better understand how CECs
      release to waterways from an FWR system compared to a conventional treatment
      system. Quantitatively, greater concentrations and total mass load of CECs was
      exhibited downstream of the conventional WWTP compared to the FWR. Average summed
      concentrations of 33 targeted CECs downstream of the conventional system were ~
      1000 ng/L and downstream of the FWR were ~ 30 ng/L. From a nontargeted chemical
      standpoint, more tentatively identified chemicals were present, and at a greater
      relative abundance, downstream of the conventional system as well. Frequently
      occurring contaminants included phthalates, pharmaceuticals, and industrial
      chemicals. These data indicate that FWR systems represent a sustainable
      wastewater treatment alternative and that emerging contaminant release to
      waterways was lower at a FWR system than a conventional WWTP.

PMID- 29460252
TI  - Seasonal variation of heavy metals in water, sediment, and highly consumed
      cultured fish (Labeo rohita and Labeo bata) and potential health risk assessment
      in aquaculture pond of the coal city, Dhanbad (India).
AB  - The extent of heavy metal pollution and their impact on the various component of
      urban aquaculture pond (India) were investigated on the basis of seasonal
      variation. The water, sediment, and fish samples (Labeo rohita and Labeo bata)
      were collected and analyzed to assess the metal toxicity. In the sediment,
      geoaccumulation index (Igeo), contamination factor (CF), pollution load index
      (PLI), and ecological risk index (ERI) were calculated. The estimated daily
      dietary intake (EDI) for As, Cd, Cr, Mn, Pb, and Zn was estimated in adult and
      children on the basis an average amount of fish consumed by the Indian people and
      its associated health hazard with was also assessed in terms of target hazard
      quotients (THQs). The concentration of metals in all the analyzed samples was
      found higher during pre-monsoon season. While, in case of fish, L. bata species
      has higher metal accumulation rate during both the seasons than the L. rohita
      because of their bottom dweller feeding habit. The order of metals in L. bata
      muscles is Zn > Mn > Pb > Cr > As > Cd. The Igeo value for Zn (2.66 to 3.68) was
      found to be highest and followed by Cd (1.65 to 3.52) and Pb (1.52 to 2.55)
      indicating moderate to highly polluted sediment quality. The values of ERI were
      significantly high during pre-monsoon period and varied from 319 to 557,
      representing very high metal contamination. From the human health perspective,
      present study highlighted that the local inhabitants who rely on this valuable
      pond for fish consumption are exposed chronically to As and Pb pollution due to
      higher THQ values, especially from the intake of L. bata.

PMID- 29460253
TI  - Neuronal apoptosis in the brainstem medulla of sudden unexpected death in infancy
      (SUDI), and the importance of standardized SUDI classification.
AB  - The purpose of this study was to examine the neuronal expression of apoptotic
      markers in the rostral medulla of a newly characterized dataset of sudden
      unexpected death in infancy (SUDI), and to determine the impact of diagnostic
      groupings on these findings and whether they pertain to the intrinsic apoptotic
      pathway. Immunohistochemical staining was quantified to determine the percentage
      of neurons positive for active caspase-9 (specific to the intrinsic apoptotic
      pathway), active caspase-3 (common to the intrinsic and extrinsic apoptotic
      pathways) and Terminal deoxynucleotidyl transferase mediated dUTP nick-end
      labelling (TUNEL) (labels DNA fragmentation) in nine nuclei of the rostral
      medulla. Expression was compared between groups of SUDI infants where the cause
      of death was initially classified by a forensic pathologist or subsequently after
      reclassification by an expert panel using the San Diego Criteria. 68 SUDI infants
      were studied and originally classified as explained SUDI (n = 12), Sudden Infant
      Death Syndrome (SIDS) (n = 27) and undetermined (n = 29). Reclassification
      resulted in a decrease in the number of explained SUDI cases to 7 and a decrease
      in the number of undetermined cases to 4, with a corresponding increase in the
      number of SIDS cases to 57 (8 SIDS I; 49 SIDS II). The expression of apoptotic
      markers was similar in explained SUDI and SIDS I infants. However, TUNEL
      expression was greater in the cuneate (p < 0.001), vestibular (p = 0.01) and
      hypoglossal (p < 0.001) nuclei and active caspase-3 expression was lower in the
      arcuate nucleus (p = 0.037) in SIDS II compared to explained Sudden Unexpected
      Death in Infancy (eSUDI) infants. Compared to SIDS I infants, SIDS II infants had
      greater TUNEL expression in the dorsal motor nucleus of the vagus (p < 0.01) and
      greater active caspase-9 expression in the medial and spinal vestibular nuclei (p
      = <0.01). Changes in apoptotic expression predominated in SIDS II infants. We
      postulate that these are due to a combination of contributing risk factors
      including the presence of an upper respiratory tract infection and bed-sharing/co
      sleeping. The absence of changes in active caspase-9 expression compared to eSUDI
      indicates that the intrinsic apoptotic pathway is not upregulated in SIDS.

PMID- 29460254
TI  - Diagnosis of arterial gas embolism in SCUBA diving: modification suggestion of
      autopsy techniques and experience in eight cases.
AB  - The purpose of this study was to suggest modifications of autopsy techniques in
      order to improve post-mortem diagnosis of arterial gas embolism (AGE) based on
      multidisciplinary investigation of SCUBA diving fatalities. Five adult human
      cadavers from the voluntary donation program of the Human Anatomy Laboratory, and
      eight judicial autopsied bodies of SCUBA divers from the Forensic Pathology
      Service were assessed. Before performing any autopsies, we accessed the diving
      plan and the divers' profiles for each case. We then introduced a new dissection
      procedure that included identification, isolation, and manipulation of carotid,
      vertebral and thoracic arterial systems. The dissected vascular structures that
      allowed optimall isolation of the systemic arterial circulation were identified
      and ligated. In three of the eight judicial cases, we had a strongly suggestive
      history of arterial gas embolism following pulmonary barotrauma (PBt/AGE). In
      these cases, the additional arterial dissection allowed us to clearly diagnose
      AGE in one of them. The autopsy of the rest of the cases showed other causes of
      death such as asphyxia by drowning and heart attack. In all cases we were able to
      reject decompression sickness, and in some of them we showed the presence of
      artefacts secondary to decomposition and resuscitation maneuvers. These results
      allow us to suggest a specific autopsy technique divided into four steps, aimed
      at confirming or excluding some evidence of dysbaric disorders according to a re
      enactment of the incident. We have demonstrated the presence of large volumes of
      intravascular air, which is typical of PBt/AGE.

PMID- 29460255
TI  - Large-scale environmental degradation results in inequitable impacts to already
      impoverished communities: A case study from the floating villages of Cambodia.
AB  - Cambodian subsistence communities within the Tonle Sap Great Lake area rely on
      resource extraction from the lake to meet livelihood needs. These fishing
      communities-many of which consist of dwellings floating on the lake-face
      potentially profound livelihood challenges because of climate change and changing
      hydrology due to dam construction for hydroelectricity within the Mekong Basin.
      We conducted interviews across five village communities, with local subsistence
      fisher people in the Tonle Sap in 2015, and used thematic analysis methods to
      reveal a fishery system that is undergoing rapid ecological decline, with local
      fishing communities increasingly experiencing reductions in available fish
      stocks. As a result, over 100 000 people living in these communities are
      experiencing a direct loss of well-being and livelihood. We discuss these losses
      and consider their implications for the future viability of Cambodian floating
      village communities.

PMID- 29460256
TI  - Post-disaster agricultural transitions in Nepal.
AB  - In Spring 2015, a series of earthquakes and aftershocks struck Nepal. The
      earthquakes caused significant changes in labor and land availability, cash
      income needs, and land quality. We examine how these post-earthquake impacts
      converged with ongoing agricultural shifts. Earthquake-related socio-economic and
      landscape changes specifically motivate the adoption of cardamom, Amomum
      subulatum, a high-value ecologically beneficial, and low labor commercial crop.
      We investigate reasons for the increased interest in cardamom post-earthquake,
      and challenges associated with it. We find that adopting cardamom serves as an
      important post-disaster adaptation. However, more broadly, unevenly distributed
      interventions coupled with the high capital costs of agricultural transition
      exacerbate social differentiation in communities after the disaster. Adoption is
      often limited to economically better off smallholder farmers. This paper extends
      previous research on disasters and smallholder farming by highlighting the
      specific potential of disasters to accelerate agricultural transitions and
      resulting inequality from the changes.

PMID- 29460257
TI  - Analysis of Postprandial Glycemia in Relation to Metabolic Compensation and Other
      Observed Parameters of Outpatients with Type 2 Diabetes Mellitus in the Czech
      Republic.
AB  - INTRODUCTION: The goal of the study was to determine the level of metabolic
      compensation expressed by glycosylated hemoglobin, fasting plasma glucose, and
      postprandial glucose as determined after a standardized breakfast; further, to
      evaluate interrelationships between the studied parameters and postprandial
      glucose levels. METHODS: The study included 1055 patients with type 2 diabetes
      mellitus. Their fasting plasma glucose and postprandial glucose were measured
      before and after a standardized breakfast. Attending diabetologists completed a
      uniform questionnaire that included demographic data, type of antidiabetic
      treatment, duration of diabetes, latest glycosylated hemoglobin value, presence
      of dyslipidemia, and organic complications. RESULTS: Glycosylated hemoglobin < 53
      mmol/mol was achieved in 363 (34.2%), postprandial glucose < 7.5 mmol/l in 211
      (19.9%), and fasting plasma glucose < 6 mmol/l in 251 (23.7%) patients. Excellent
      metabolic compensation, indicated by all the above mentioned glycosylated
      hemoglobin, fasting plasma glucose, and postprandial glucose values
      simultaneously, was achieved in only 71 (6.7%) patients. Comparable to fasting
      plasma glucose and postprandial glucose values, correlation with glycosylated
      hemoglobin levels is statistically significant; however, there is no difference
      at different glycosylated hemoglobin levels. There was a significant correlation
      between dyslipidemia and postprandial glycemia (p = 0.013). CONCLUSION: The
      objective of care for patients with diabetes mellitus is to improve their long
      term metabolic compensation; to that end, both fasting plasma glucose and
      postprandial glucose deserve equal attention.

PMID- 29460258
TI  - Diabetes in the Elderly.
AB  - The elderly are an important and distinct yet heterogeneous group of persons
      living with diabetes. The elderly have a unique biomedical, psychological, and
      social constitution. Their needs are different from those of younger adults. This
      implies that special care must be taken while evaluating and planning their
      nursing and management. Diabetes management in the elderly should focus on
      prevention and limitation of geriatric syndromes (medical conditions encountered
      in elderly persons), hypoglycemia (low blood glucose), and neurocognitive
      dysfunction (impairment in the functioning of the nervous system and brain). This
      review takes a practical approach to the assessment, nursing care, and medical
      treatment of diabetes in the elderly. It highlights major challenges and suggests
      solutions to these commonly encountered clinical problems.

PMID- 29460259
TI  - Glucagon-Like Peptide-1 Receptor Agonist Use and Renal Impairment: A
      Retrospective Analysis of an Electronic Health Records Database in the U.S.
      Population.
AB  - INTRODUCTION: The study characterizes the use of glucagon-like peptide-1 receptor
      agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) with and without
      renal impairment and examines the effects of such use on the clinical outcomes of
      estimated glomerular filtration rate (eGFR) and glycated hemoglobin (A1c).
      METHODS: Data from the Practice Fusion electronic health records database from 1
      January 2012 through 30 April 2015 were used. Adults with T2D who received serum
      creatinine laboratory tests and initiated therapy with a GLP-1 RA (N = 3225) or
      other glucose-lowering agent (GLA) (N = 37,074) were included in the analysis.
      The GLP-1 RA cohort was matched to cohorts initiating therapy any other GLA, and
      multivariable analyses examined the association between GLP-1 RA use and changes
      in eGFR or A1c at 1 year after therapy initiation. RESULTS: In this study, only
      5.7% of patients with an eGFR of < 30 and >= 15 mL/min/1.73 m2 and 3.6% of
      patients with an eGFR of  < 15 mL/min/1.73 m2 initiated therapy with a GLP-1 RA.
      Compared to other GLAs, at 1-year after initiation of therapy the use of a GLP-1
      RA was associated with a significantly smaller decline in eGFR (- 0.80 vs. - 1.03
      mL/min/1.73 m2; P = 0.0005), a significantly smaller likelihood of having a >=
      30% reduction in eGFR (2.19 vs. 3.14%; P < 0.0001), and a significantly larger
      reduction in A1c (- 0.48 vs. - 0.43; P = 0.0064). CONCLUSION: In clinical
      practice, the use of GLP-1 RAs in patients with a higher degree of renal
      impairment disease was limited. Compared to other GLAs, the use of GLP-1 RAs was
      associated with a significantly smaller decline in eGFR and a larger reduction in
      A1c over the 1 year following therapy initiation. FUNDING: Eli Lilly and Company.

PMID- 29460260
TI  - Clinical Benefit of Basal Insulin Analogue Treatment in Persons with Type 2
      Diabetes Inadequately Controlled on Prior Insulin Therapy: A Prospective,
      Noninterventional, Multicenter Study.
AB  - INTRODUCTION: Basal insulin analogues offer persons with type 2 diabetes mellitus
      (T2DM) adequate glycemic control combined with a favorable safety profile. BASAL
      BALI-a prospective, noninterventional, multicenter disease registry-assessed the
      effectiveness and safety of basal insulin analogues in adult Serbians with T2DM
      previously inadequately controlled on other insulin types. METHODS: The primary
      objective was to assess the reduction in glycated hemoglobin (HbA1c) from basal
      insulin analogue initiation to the end of a 6-month observation period. Data
      collection was performed at three study visits: baseline, 3 months, and 6 months.
      All treatments and procedures were performed at the physicians' discretion.
      RESULTS: In total, 460 subjects were included. Mean diabetes duration was 11.6 +/
      6.6 years. Late complications of diabetes were present in 67% of subjects and
      comorbidities in 85%. After 6 months, the mean reduction in HbA1c was 1.8% (p <
      0.01 vs. baseline); body weight (mean reduction of 0.9 kg, p < 0.01), waist
      circumference (1.5 cm, p < 0.01), and BMI (0.2 kg/m2, p < 0.01) were also
      reduced. A total of 49.1% of subjects reached their individualized HbA1c
      treatment target, and 42.0% met the composite HbA1c and fasting plasma glucose
      (FPG) target. The incidence of symptomatic hypoglycemia was reduced from 96.3% in
      the 6 months prior to initiating basal insulin analogues to 15.4% over the 6
      month treatment period. CONCLUSION: Introducing basal insulin analogues in
      persons with T2DM previously inadequately controlled on other insulin types can
      significantly improve glycemic control and reduce the risk of hypoglycemia,
      without adversely affecting body weight. FUNDING: Sanofi, Serbia.

PMID- 29460261
TI  - Baseline and changes in serum uric acid independently predict 11-year incidence
      of metabolic syndrome among community-dwelling women.
AB  - INTRODUCTION: Metabolic syndrome (MetS) is associated with an increased risk of
      major cardiovascular events. In women, increased serum uric acid (SUA) levels are
      associated with MetS and its components. However, whether baseline and changes in
      SUA predict incidence of MetS and its components remains unclear. METHODS: The
      subjects comprised 407 women aged 71 +/- 8 years from a rural village. We have
      identified participants who underwent a similar examination 11 years ago, and
      examined the relationship between baseline and changes in SUA, and MetS based on
      the modified criteria of the National Cholesterol Education Program's Adult
      Treatment Panel (NCEP-ATP) III report. RESULTS: Of these subjects, 83 (20.4%)
      women at baseline and 190 (46.7%) women at follow-up had MetS. Multiple linear
      regression analysis was performed to evaluate the contribution of each
      confounding factor for MetS; both baseline and changes in SUA as well as history
      of cardiovascular disease, low-density lipoprotein cholesterol, and estimated
      glomerular filtration ratio (eGFR) were independently and significantly
      associated with the number of MetS components during an 11-year follow-up. The
      adjusted odds ratios (ORs) (95% confidence interval) for incident MetS across
      tertiles of baseline SUA and changes in SUA were 1.00, 1.47 (0.82-2.65), and 3.11
      (1.66-5.83), and 1.00, 1.88 (1.03-3.40), and 2.49 (1.38-4.47), respectively. In
      addition, the combined effect between increased baseline and changes in SUA was
      also a significant and independent determinant for the accumulation of MetS
      components (F = 20.29, p < 0.001). The ORs for incident MetS were significant
      only in subjects with age >= 55 years, decline in eGFR, and no baseline MetS.
      CONCLUSIONS: These results suggested that combined assessment of baseline and
      changes in SUA levels provides increased information for incident MetS,
      independent of other confounding factors in community-dwelling women.

PMID- 29460263
TI  - Methadone as anticancer treatment: hype, hope, or hazard? : A series of case
      reports and a short review of the current literature and recommendations of the
      societies.
AB  - Recently, the use of methadone in cancer patients has increased due to in vitro
      studies indicating that methadone is capable of inducing cell death. However,
      thus far there are no relevant clinical studies indicating that the use of
      methadone can prolong survival in cancer patients. Based on low-quality evidence,
      methadone is a drug that has similar analgesic benefits to morphine and has a
      role in the management of cancer pain in adults. Other opioids such as morphine,
      hydromorphone, and fentanyl are easier to manage but may be more expensive than
      methadone in many economies. Methadone is an opioid that is only approved for
      replacement therapy in Austria. Methadone can be used as a second- or third-line
      agent for severe cancer-related pain, but its use should be restricted to
      experts. Here we report a series of cases of patients who developed problems when
      using methadone as an antitumor treatment, with a brief review on the role of
      methadone as a pain medication and the current lack of value as an anti-tumor
      therapy. Methadone is not approved or recommended as an anticancer treatment in
      Austria or Germany. The Austrian Association for Hemato-oncology (OeGHO), the
      Austrian Association for the Management of Pain (OSG), and the Austrian
      Association for Palliative Care (OPG) do not recommend the use of methadone as an
      anticancer treatment. Thus, from a medical and ethical point of view, the use of
      methadone as an antitumor therapy is to be rejected, based on the views of
      various Austrian (OeGHO, OSG, OPG) and German specialists. Unqualified use of
      methadone by nonexperienced pain therapists is dangerous and must also be
      rejected.

PMID- 29460264
TI  - Acute myopathy as a side effect of electrostimulation.

PMID- 29460262
TI  - Physiologic effects of voice stimuli in conscious and unconscious palliative
      patients-a pilot study.
AB  - BACKGROUND: Sounds and acoustic stimuli can have an effect on human beings. In
      medical care, sounds are often used as parts of therapies, e. g., in different
      types of music therapies. Also, human speech greatly affects the mental status.
      Although calming sounds and music are widely established in the medical field,
      clear evidence for the effect of sounds in palliative care is scare, and data
      about effects of the human voice in general are still missing. Thus, the aim of
      this study was to evaluate the effects of different voice stimuli on palliative
      patients. METHODS: Two different voice stimuli (one calm, the other turbulent)
      were presented in a randomized sequence, and physiological parameters (blood
      pressure, heart frequency, oxygen saturation, respiratory rate) were recorded.
      RESULTS: Twenty patients (14 conscious and 6 unconscious) participated in this
      study. There was a decrease of heart frequency as well as an increase of oxygen
      saturation in the group of conscious patients, whereas no significant change of
      blood pressure or respiratory rate were detected in either group, conscious and
      unconscious patients. CONCLUSIONS: Although our dataset is heterogeneous, it can
      be concluded that voice stimuli can influence conscious patients. However, in
      this setting, no effect on unconscious patients was demonstrated. More clinical
      research on this topic with larger groups and a broader spectrum of parameters is
      needed.

PMID- 29460265
TI  - miRNA Editing: New Insights into the Fast Control of Gene Expression in Health
      and Disease.
AB  - Post-transcriptional modifications are essential mechanisms for mRNA biogenesis
      and function in eukaryotic cells. Beyond well-characterized events such as
      splicing, capping, and polyadenylation, there are several others, as RNA editing
      mechanisms and regulation of transcription mediated by miRNAs that are taking
      increasing attention in the last years. RNA editing through A-to-I deamination
      increases transcriptomic complexity, generating different proteins with amino
      acid substitution from the same transcript. On the other hand, miRNAs can
      regulate gene expression modulating target mRNA decay and translation.
      Interestingly, recent studies highlight the possibility that miRNAs might undergo
      editing themselves. This mainly translates in the degradation or uncorrected
      maturation of miRNAs but also in the recognition of different targets. The
      presence of edited and unedited forms of the same miRNA may have important
      biological implications in both health and disease. Here we review ongoing
      investigations on miRNA RNA editing with the aim to shed light on the growing
      importance of this mechanism in adding complexity to post-transcriptional
      regulation of gene expression.

PMID- 29460266
TI  - Increased Levels of Rictor Prevent Mutant Huntingtin-Induced Neuronal
      Degeneration.
AB  - Rictor associates with mTOR to form the mTORC2 complex, which activity regulates
      neuronal function and survival. Neurodegenerative diseases are characterized by
      the presence of neuronal dysfunction and cell death in specific brain regions
      such as for example Huntington's disease (HD), which is characterized by the loss
      of striatal projection neurons leading to motor dysfunction. Although HD is
      caused by the expression of mutant huntingtin, cell death occurs gradually
      suggesting that neurons have the capability to activate compensatory mechanisms
      to deal with neuronal dysfunction and later cell death. Here, we analyzed whether
      mTORC2 activity could be altered by the presence of mutant huntingtin. We
      observed that Rictor levels are specifically increased in the striatum of HD
      mouse models and in the putamen of HD patients. Rictor-mTOR interaction and the
      phosphorylation levels of Akt, one of the targets of the mTORC2 complex, were
      increased in the striatum of the R6/1 mouse model of HD suggesting increased
      mTORC2 signaling. Interestingly, acute downregulation of Rictor in striatal cells
      in vitro reduced mTORC2 activity, as shown by reduced levels of phospho-Akt, and
      increased mutant huntingtin-induced cell death. Accordingly, overexpression of
      Rictor increased mTORC2 activity counteracting cell death. Furthermore,
      normalization of endogenous Rictor levels in the striatum of R6/1 mouse worsened
      motor symptoms suggesting an induction of neuronal dysfunction. In conclusion,
      our results suggest that increased Rictor striatal levels could counteract
      neuronal dysfunction induced by mutant huntingtin.

PMID- 29460267
TI  - Hypoxia-Preconditioned Human Umbilical Vein Endothelial Cells Protect Against
      Neurovascular Damage After Hypoxic Ischemia in Neonatal Brain.
AB  - Therapy targeting the neurovascular unit may provide effective neuroprotection
      against neonatal hypoxia-ischemia (HI). We hypothesized that the peripheral
      injection of hypoxia-preconditioned human umbilical vein endothelial cells
      (HUVECs) following HI protects against neurovascular damage and provides long
      term neuroprotection in a postpartum (P) day-7 rat pup model. Compared with
      normoxic HUVECs, hypoxic HUVECs showed enhanced migration and angiogenesis in
      vitro and had augmented migration effects into the brain when administered
      intraperitoneally in vivo after HI. Moreover, 24 and 72 h post-HI, the hypoxic
      HUVECs group but not the normoxic HUVECs or culture-medium groups had
      significantly higher preservation of microvessels and neurons, and attenuation of
      blood-brain barrier damage than the normal-saline group. Compared to control or
      normal-saline groups, only the hypoxic HUVECs group had no impaired foot steps
      and showed a significant reduction of brain area loss at P42. Next-generation
      sequencing showed hypoxia-induced upregulation and downregulation of 209 and 215
      genes in HUVECs, respectively. Upstream regulator analysis by ingenuity pathway
      analysis (IPA) identified hypoxia-inducible factor 1-alpha as the key predicted
      activated transcription regulator. After hypoxia, 12 genes (ADAMTS1, EFNA1,
      HIF1A, LOX, MEOX2, SELE, VEGFA, VEGFC, CX3CL1, HMMR, SDC, and SERPINE) associated
      with migration and/or angiogenesis were regulated in HUVECs. In addition, 6 genes
      (VEGFA, VEGFC, NTN4, TGFA, SERPINE1, and CX3CL1) involved in the survival of
      endothelial and neuronal cells were also markedly altered in hypoxic HUVECs.
      Thus, cell therapy by using hypoxic HUVECs that enhance migration and
      neurovascular protection may provide an effective therapeutic strategy for
      treating neonatal asphyxia.

PMID- 29460268
TI  - Interaction of Peptide Aptamers with Prion Protein Central Domain Promotes alpha
      Cleavage of PrPC.
AB  - Prion diseases are infectious and fatal neurodegenerative diseases affecting
      humans and animals. Transmission is possible within and between species with
      zoonotic potential. Currently, no prophylaxis or treatment exists. Prions are
      composed of the misfolded isoform PrPSc of the cellular prion protein PrPC.
      Expression of PrPC is a prerequisite for prion infection, and conformational
      conversion of PrPC is induced upon its direct interaction with PrPSc. Inhibition
      of this interaction can abrogate prion propagation, and we have previously
      established peptide aptamers (PAs) binding to PrPC as new anti-prion compounds.
      Here, we mapped the interaction site of PA8 in PrP and modeled the complex in
      silico to design targeted mutations in PA8 which presumably enhance binding
      properties. Using these PA8 variants, we could improve PA-mediated inhibition of
      PrPSc replication and de novo infection of neuronal cells. Furthermore, we
      demonstrate that binding of PA8 and its variants increases PrPC alpha-cleavage
      and interferes with its internalization. This gives rise to high levels of the
      membrane-anchored PrP-C1 fragment, a transdominant negative inhibitor of prion
      replication. PA8 and its variants interact with PrPC at its central and most
      highly conserved domain, a region which is crucial for prion conversion and
      facilitates toxic signaling of Abeta oligomers characteristic for Alzheimer's
      disease. Our strategy allows for the first time to induce alpha-cleavage, which
      occurs within this central domain, independent of targeting the responsible
      protease. Therefore, interaction of PAs with PrPC and enhancement of alpha
      cleavage represent mechanisms that can be beneficial for the treatment of prion
      and other neurodegenerative diseases.

PMID- 29460269
TI  - Novel Defense by Metallothionein Induction Against Cognitive Decline: From
      Amyloid beta1-42-Induced Excess Zn2+ to Functional Zn2+ Deficiency.
AB  - The role of metallothioneins (MTs) in cognitive decline associated with
      intracellular Zn2+ dysregulation remains unclear. Here, we report that
      hippocampal MT induction defends cognitive decline, which was induced by amyloid
      beta1-42 (Abeta1-42)-mediated excess Zn2+ and functional Zn2+ deficiency. Excess
      increase in intracellular Zn2+, which was induced by local injection of Abeta1-42
      into the dentate granule cell layer, attenuated in vivo perforant pathway LTP,
      while the attenuation was rescued by preinjection of MT inducers into the same
      region. Intraperitoneal injection of dexamethasone, which increased hippocampal
      MT proteins and blocked Abeta1-42-mediated Zn2+ uptake, but not Abeta1-42 uptake,
      into dentate granule cells, also rescued Abeta1-42-induced impairment of memory
      via attenuated LTP. The present study indicates that hippocampal MT induction
      blocks rapid excess increase in intracellular Zn2+ in dentate granule cells,
      which originates in Zn2+ released from Abeta1-42, followed by rescuing Abeta1-42
      induced cognitive decline. Furthermore, LTP was vulnerable to Abeta1-42 in the
      aged dentate gyrus, consistent with enhanced Abeta1-42-mediated Zn2+ uptake into
      aged dentate granule cells, suggesting that Abeta1-42-induced cognitive decline,
      which is caused by excess intracellular Zn2+, can more frequently occur along
      with aging. On the other hand, attenuated LTP under functional Zn2+ deficiency in
      dentate granule cells was also rescued by MT induction. Hippocampal MT induction
      may rescue cognitive decline under lack of cellular transient changes in
      functional Zn2+ concentration, while its induction is an attractive defense
      strategy against Abeta1-42-induced cognitive decline.

PMID- 29460271
TI  - SERPINA1 Gene Variants in Granulomatosis with Polyangiitis.
AB  - Alpha-1 antitrypsin (A1AT) deficiency is one of the most common genetic disorders
      in Caucasian population. There is a link between granulomatosis with polyangiitis
      (GPA) and most frequent variants of SERPINA1 gene encoding severe alpha-1
      antitripsin deficiency. However, the potential effect of Pi*Z, Pi*S as well as
      other SERPINA1 variants on clinical course of vasculitis are not well understood.
      The aim of the study was to analyze the potential effect of A1AT protein
      phenotype representing the SERPINA1 gene variants on the clinical course of GPA.
      The study group consisted of 64 subjects with GPA, stratified according to the
      disease severity: patients in active phase (group I, n = 12), patients during
      remission on treatment (group II, n = 40) or untreated (group III, n = 12).
      Normal Pi*MM SERPINA1 genotype was detected by means of real-time polymerase
      chain reaction (PCR) or direct sequencing in 59 patients, Pi*MZ genotype in 2,
      and Pi*IM, Pi*MS or Pi*SZ in 1 patient respectively. The patients with abnormal
      Pi*Z, Pi*S, or Pi*I allele constituted 17% in group I, 5% in group II, and 8% in
      group III. The serum content of A1AT and high sensitivity C-reactive protein
      (hsCRP) assessed by nephelometry did not differ between the groups.
      Interestingly, the mean serum antiPR3-antibodies level detected by Elisa method
      was significantly greater in the GPA patients with Pi*Z, Pi*S, or Pi*I SERPINA1
      variants than in the Pi*MM homozygotes. In summary, heterozygous Pi*MZ, Pi*MS,
      and Pi*SZ genotype was detected in 7.8% of total group of GPA patients, and in
      10.5% of those with lung lesions. The abnormal alleles of Pi*S and Pi*Z may
      affect the clinical course of the disease.

PMID- 29460270
TI  - Towards a TDP-43-Based Biomarker for ALS and FTLD.
AB  - TDP-43 accumulates in nerve cells of nearly all cases of amyotrophic lateral
      sclerosis (ALS; the commonest form of motor neuron disease) and in the majority
      of Tau-negative frontotemporal lobar degeneration (FTLD). There is currently no
      biochemical test or marker of disease activity for ALS or FTLD, and the clinical
      diagnosis depends on the opinion of an experienced neurologist. TDP-43 has a key
      role in the pathogenesis of ALS/FTLD. Measuring TDP-43 in easily accessible
      biofluids, such as blood or cerebrospinal fluid, might reduce diagnostic delay
      and offer a readout for use in future drug trials. However, attempts at measuring
      disease-specific forms of TDP-43 in peripheral biofluids of ALS and FTLD patients
      have not yielded consistent results, and only some of the pathological
      biochemical features of TDP-43 found in human brain tissue have been detected in
      clinical biofluids to date. Reflecting on the molecular pathology of TDP-43, this
      review provides a critical overview on biofluid studies and future directions to
      develop a TDP-43-based clinical biomarker for ALS and FTLD.

PMID- 29460272
TI  - Hyperglycemia in Children Hospitalized with Acute Asthma.
AB  - Hyperglycemia is frequently observed in adults with acute asthma. We aimed to
      assess the frequency of hyperglycemia and its relation to outcomes in children
      admitted with acute asthma. In this retrospective study, we reviewed medical
      records of non-diabetic 166 children (66 girls) with the mean age of 5.4 +/- 2.6
      years (range of 2-12 years), who were hospitalized with acute asthma between
      January 2012 through December 2014. Data pertaining to demographics, vital signs,
      oxygen saturation, serum blood glucose level, electrolytes, blood gases, and
      admission were collected. Children with other chronic conditions were excluded.
      The findings were that hyperglycemia (blood glucose >= 11.1 mmol/l) was observed
      in 38.6% of children. The median baseline blood glucose (IQR) was 9.8 mmol/l (7.2
      13.3 mmol/l). Blood glucose level was associated with the length of
      hospitalization, with a median extension of 1.8 days, but was inversely
      associated with the serum potassium and bicarbonate levels. There were no
      associations between baseline blood glucose and age, gender, baseline respiratory
      rate, oxygen saturation, or intensive care admission. Hyperglycemia resolved
      spontaneously in all affected children. We conclude that hyperglycemia is common
      in children hospitalized with acute asthma. Hyperglycemia could be considered as
      a marker of a longer hospital stay.

PMID- 29460273
TI  - Pharmacogenetic Information in Clinical Guidelines: The European Perspective.
AB  - Surveys among pharmacists and physicians show that these healthcare professionals
      have successfully adopted the concept of pharmacogenomics (PGx).1-3 In addition,
      patients are willing to consent to participate in PGx implementation studies.4
      However, the surveys also show that healthcare professionals do not frequently
      order or recommend a PGx test.1,2 Among others, a frequently perceived hurdle for
      clinical uptake of PGx is the availability of guidelines translating PGx test
      results into clinical actions for individual patients.5,6.

PMID- 29460274
TI  - A perfusion chamber for monitoring transepithelial NaCl transport in an in vitro
      model of the renal tubule.
AB  - Transepithelial electrical measurements in the renal tubule have provided a
      better understanding of how kidney regulates electrolyte and water homeostasis
      through the reabsorption of molecules and ions (e.g., H2 O and NaCl). While
      experiments and measurement techniques using native tissue are difficult to
      prepare and to reproduce, cell cultures conducted largely with the Ussing chamber
      lack the effect of fluid shear stress which is a key physiological stimulus in
      the renal tubule. To overcome these limitations, we present a modular perfusion
      chamber for long-term culture of renal epithelial cells under flow that allows
      the continuous and simultaneous monitoring of both transepithelial electrical
      parameters and transepithelial NaCl transport. The latter is obtained from
      electrical conductivity measurements since Na+ and Cl- are the ions that
      contribute most to the electrical conductivity of a standard physiological
      solution. The system was validated with epithelial monolayers of raTAL and NRK
      52E cells that were characterized electrophysiologically for 5 days under
      different flow conditions (i.e., apical perfusion, basal, or both). In addition,
      apical to basal chemical gradients of NaCl (140/70 and 70/140 mM) were imposed in
      order to demonstrate the feasibility of this methodology for quantifying and
      monitoring in real time the transepithelial reabsorption of NaCl, which is a
      primary function of the renal tubule.

PMID- 29460275
TI  - Community screening for visual impairment in older people.
AB  - BACKGROUND: Visual problems in older people are common and frequently under
      reported. The effects of poor vision in older people are wide reaching and
      include falls, confusion and reduced quality of life. Much of the visual
      impairment in older ages can be treated (e.g. cataract surgery, correction of
      refractive error). Vision screening may therefore reduce the number of older
      people living with sight loss. OBJECTIVES: The objective of this review was to
      assess the effects on vision of community vision screening of older people for
      visual impairment. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials
      Register) (2017, Issue 10); Ovid MEDLINE; Ovid Embase; the ISRCTN registry;
      ClinicalTrials.gov and the ICTRP. The date of the search was 23 November 2017.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared
      vision screening alone or as part of a multi-component screening package as
      compared to no vision screening or standard care, on the vision of people aged 65
      years or over in a community setting. We included trials that used self-reported
      visual problems or visual acuity testing as the screening tool. DATA COLLECTION
      AND ANALYSIS: We used standard methods expected by Cochrane. We graded the
      certainty of the evidence using GRADE. MAIN RESULTS: Visual outcome data were
      available for 10,608 people in 10 trials. Four trials took place in the UK, two
      in Australia, two in the United States and two in the Netherlands. Length of
      follow-up ranged from one to five years. Three of these studies were cluster
      randomised trials whereby general practitioners or family physicians were
      randomly allocated to undertake vision screening or no vision screening. All
      studies were funded by government agencies. Overall we judged the studies to be
      at low risk of bias and only downgraded the certainty of the evidence (GRADE) for
      imprecision.Seven trials compared vision screening as part of a multi-component
      screening versus no screening. Six of these studies used self-reported vision as
      both screening tool and outcome measure, but did not directly measure vision. One
      study used a combination of self-reported vision and visual acuity measurement:
      participants reporting vision problems at screening were treated by the attending
      doctor, referred to an eye care specialist or given information about resources
      that were available to assist with poor vision. There was a similar risk of "not
      seeing well" at follow-up in people screened compared with people not screened in
      meta-analysis of six studies (risk ratio (RR) 1.05, 95% confidence interval (CI)
      0.97 to 1.14, 4522 participants high-certainty evidence). One trial reported
      "improvement in vision" and this occurred slightly less frequently in the
      screened group (RR 0.85, 95% CI 0.52 to 1.40, 230 participants, moderate
      certainty evidence).Two trials compared vision screening (visual acuity testing)
      alone with no vision screening. In one study, distance visual acuity was similar
      in the two groups at follow-up (mean difference (MD) 0.02 logMAR, 95% CI -0.02 to
      0.05, 532 participants, high-certainty evidence). There was also little
      difference in near acuity (MD 0.02 logMAR, 95% CI -0.03 to 0.07, 532
      participants, high-certainty evidence). There was no evidence of any important
      difference in quality of life (MD -0.06 National Eye Institute 25-item visual
      function questionnaire (VFQ-25) score adjusted for baseline VFQ-25 score, 95% CI 
      2.3 to 1.1, 532 participants, high-certainty evidence). The other study could not
      be included in the data analysis as the number of participants in each of the
      arms at follow-up could not be determined. However the authors stated that there
      was no significant difference in mean visual acuity in participants who had
      visual acuity assessed at baseline (39 letters) as compared to those who did not
      have their visual acuity assessed (35 letters, P = 0.25, 121 participants).One
      trial compared a detailed health assessment including measurement of visual
      acuity (intervention) with a brief health assessment including one question about
      vision (standard care). People given the detailed health assessment had a similar
      risk of visual impairment (visual acuity worse than 6/18 in either eye) at follow
      up compared with people given the brief assessment (RR 1.07, 95% CI 0.84 to 1.36,
      1807 participants, moderate-certainty evidence). The mean composite score of the
      VFQ-25 was 86.0 in the group that underwent visual acuity screening compared with
      85.6 in the standard care group, a difference of 0.40 (95% CI -1.70 to 2.50, 1807
      participants, high-certainty evidence). AUTHORS' CONCLUSIONS: The evidence from
      RCTs undertaken to date does not support vision screening for older people living
      independently in a community setting, whether in isolation or as part of a multi
      component screening package. This is true for screening programmes involving
      questions about visual problems, or direct measurements of visual acuity.The most
      likely reason for this negative review is that the populations within the trials
      often did not take up the offered intervention as a result of the vision
      screening and large proportions of those who did not have vision screening
      appeared to seek their own intervention. Also, trials that use questions about
      vision have a lower sensitivity and specificity than formal visual acuity
      testing. Given the importance of visual impairment among older people, further
      research into strategies to improve vision of older people is needed. The
      effectiveness of an optimised primary care-based screening intervention that
      overcomes possible factors contributing to the observed lack of benefit in trials
      to date warrants assessment; trials should consider including more dependent
      participants, rather than those living independently in the community.

PMID- 29460276
TI  - Surgery for trigger finger.
AB  - BACKGROUND: Trigger finger is a common clinical disorder, characterised by pain
      and catching as the patient flexes and extends digits because of disproportion
      between the diameter of flexor tendons and the A1 pulley. The treatment approach
      may include non-surgical or surgical treatments. Currently there is no consensus
      about the best surgical treatment approach (open, percutaneous or endoscopic
      approaches). OBJECTIVES: To evaluate the effectiveness and safety of different
      methods of surgical treatment for trigger finger (open, percutaneous or
      endoscopic approaches) in adults at any stage of the disease. SEARCH METHODS: We
      searched CENTRAL, MEDLINE, Embase and LILACS up to August 2017. SELECTION
      CRITERIA: We included randomised or quasi-randomised controlled trials that
      assessed adults with trigger finger and compared any type of surgical treatment
      with each other or with any other non-surgical intervention. The major outcomes
      were the resolution of trigger finger, pain, hand function, participant-reported
      treatment success or satisfaction, recurrence of triggering, adverse events and
      neurovascular injury. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected the trial reports, extracted the data and assessed the
      risk of bias. Measures of treatment effect for dichotomous outcomes calculated
      risk ratios (RRs), and mean differences (MDs) or standardised mean differences
      (SMD) for continuous outcomes, with 95% confidence intervals (CIs). When
      possible, the data were pooled into meta-analysis using the random-effects model.
      GRADE was used to assess the quality of evidence for each outcome. MAIN RESULTS:
      Fourteen trials were included, totalling 1260 participants, with 1361 trigger
      fingers. The age of participants included in the studies ranged from 16 to 88
      years; and the majority of participants were women (approximately 70%). The
      average duration of symptoms ranged from three to 15 months, and the follow-up
      after the procedure ranged from eight weeks to 23 months.The studies reported
      nine types of comparisons: open surgery versus steroid injections (two studies);
      percutaneous surgery versus steroid injection (five studies); open surgery versus
      steroid injection plus ultrasound-guided hyaluronic acid injection (one study);
      percutaneous surgery plus steroid injection versus steroid injection (one study);
      percutaneous surgery versus open surgery (five studies); endoscopic surgery
      versus open surgery (one study); and three comparisons of types of incision for
      open surgery (transverse incision of the skin in the distal palmar crease,
      transverse incision of the skin about 2-3 mm distally from distal palmar crease,
      and longitudinal incision of the skin) (one study).Most studies had significant
      methodological flaws and were considered at high or unclear risk of selection
      bias, performance bias, detection bias and reporting bias. The primary comparison
      was open surgery versus steroid injections, because open surgery is the oldest
      and the most widely used treatment method and considered as standard surgery,
      whereas steroid injection is the least invasive control treatment method as
      reported in the studies in this review and is often used as first-line treatment
      in clinical practice.Compared with steroid injection, there was low-quality
      evidence that open surgery provides benefits with respect to less triggering
      recurrence, although it has the disadvantage of being more painful. Evidence was
      downgraded due to study design flaws and imprecision.Based on two trials (270
      participants) from six up to 12 months, 50/130 (or 385 per 1000) individuals had
      recurrence of trigger finger in the steroid injection group compared with 8/140
      (or 65 per 1000; range 35 to 127) in the open surgery group, RR 0.17 (95% CI 0.09
      to 0.33), for an absolute risk difference that 29% fewer people had recurrence of
      symptoms with open surgery (60% fewer to 3% more individuals); relative change
      translates to improvement of 83% in the open surgery group (67% to 91% better).At
      one week, 9/49 (184 per 1000) people had pain on the palm of the hand in the
      steroid injection group compared with 38/56 (or 678 per 1000; ranging from 366 to
      1000) in the open surgery group, RR 3.69 (95% CI 1.99 to 6.85), for an absolute
      risk difference that 49% more had pain with open surgery (33% to 66% more);
      relative change translates to worsening of 269% (585% to 99% worse) (one trial,
      105 participants).Because of very low quality evidence from two trials we are
      uncertain whether open surgery improve resolution of trigger finger in the follow
      up at six to 12 months, when compared with steroid injection (131/140 observed in
      the open surgery group compared with 80/130 in the control group; RR 1.48, 95% CI
      0.79 to 2.76); evidence was downgraded due to study design flaws, inconsistency
      and imprecision. Low-quality evidence from two trials and few event rates (270
      participants) from six up to 12 months of follow-up, we are uncertain whether
      open surgery increased the risk of adverse events (incidence of infection, tendon
      injury, flare, cutaneous discomfort and fat necrosis) (18/140 observed in the
      open surgery group compared with 17/130 in the control group; RR 1.02, 95% CI
      0.57 to 1.84) and neurovascular injury (9/140 observed in the open surgery group
      compared with 4/130 in the control group; RR 2.17, 95% CI 0.7 to 6.77). Twelve
      participants (8 versus 4) did not complete the follow-up, and it was considered
      that they did not have a positive outcome in the data analysis. We are uncertain
      whether open surgery was more effective than steroid injection in improving hand
      function or participant satisfaction as studies did not report these outcomes.
      AUTHORS' CONCLUSIONS: Low-quality evidence indicates that, compared with steroid
      injection, open surgical treatment in people with trigger finger, may result in a
      less recurrence rate from six up to 12 months following the treatment, although
      it increases the incidence of pain during the first follow-up week. We are
      uncertain about the effect of open surgery with regard to the resolution rate in
      follow-up at six to 12 months, compared with steroid injections, due high
      heterogeneity and few events occurred in the trials; we are uncertain too about
      the risk of adverse events and neurovascular injury because of a few events
      occurred in the studies. Hand function or participant satisfaction were not
      reported.

PMID- 29460277
TI  - Plant responses to fertilization experiments in lowland, species-rich, tropical
      forests.
AB  - We present a meta-analysis of plant responses to fertilization experiments
      conducted in lowland, species-rich, tropical forests. We also update a key result
      and present the first species-level analyses of tree growth rates for a 15-yr
      factorial nitrogen (N), phosphorus (P), and potassium (K) experiment conducted in
      central Panama. The update concerns community-level tree growth rates, which
      responded significantly to the addition of N and K together after 10 yr of
      fertilization but not after 15 yr. Our experimental soils are infertile for the
      region, and species whose regional distributions are strongly associated with low
      soil P availability dominate the local tree flora. Under these circumstances, we
      expect muted responses to fertilization, and we predicted species associated with
      low-P soils would respond most slowly. The data did not support this prediction,
      species-level tree growth responses to P addition were unrelated to species-level
      soil P associations. The meta-analysis demonstrated that nutrient limitation is
      widespread in lowland tropical forests and evaluated two directional hypotheses
      concerning plant responses to N addition and to P addition. The meta-analysis
      supported the hypothesis that tree (or biomass) growth rate responses to
      fertilization are weaker in old growth forests and stronger in secondary forests,
      where rapid biomass accumulation provides a nutrient sink. The meta-analysis
      found no support for the long-standing hypothesis that plant responses are
      stronger for P addition and weaker for N addition. We do not advocate discarding
      the latter hypothesis. There are only 14 fertilization experiments from lowland,
      species-rich, tropical forests, 13 of the 14 experiments added nutrients for five
      or fewer years, and responses vary widely among experiments. Potential
      fertilization responses should be muted when the species present are well adapted
      to nutrient-poor soils, as is the case in our experiment, and when pest pressure
      increases with fertilization, as it does in our experiment. The statistical power
      and especially the duration of fertilization experiments conducted in old growth,
      tropical forests might be insufficient to detect the slow, modest growth
      responses that are to be expected.

PMID- 29460279
TI  - Bier spots treated with intense pulsed light.

PMID- 29460278
TI  - Structural and metabolic responses of Staphylococcus aureus biofilms to
      hyperosmotic and antibiotic stress.
AB  - Biofilms alter their metabolism in response to environmental stress. This study
      explores the effect of a hyperosmotic agent-antibiotic treatment on the
      metabolism of Staphylococcus aureus biofilms through the use of nuclear magnetic
      resonance (NMR) techniques. To determine the metabolic activity of S. aureus, we
      quantified the concentrations of metabolites in spent medium using high
      resolution NMR spectroscopy. Biofilm porosity, thickness, biovolume, and relative
      diffusion coefficient depth profiles were obtained using NMR microimaging.
      Dissolved oxygen concentration was measured to determine the availability of
      oxygen within the biofilm. Under vancomycin-only treatment, the biofilm
      communities switched to fermentation under anaerobic condition, as evidenced by
      high concentrations of formate (7.4 +/- 2.7 mM), acetate (13.1 +/- 0.9 mM), and
      lactate (3.0 +/- 0.8 mM), and there was no detectable dissolved oxygen in the
      biofilm. In addition, we observed the highest consumption of pyruvate (0.19 mM
      remaining from an initial 40 mM concentration), the sole carbon source, under the
      vancomycin-only treatment. On the other hand, relative effective diffusion
      coefficients increased from 0.73 +/- 0.08 to 0.88 +/- 0.08 under vancomycin-only
      treatment but decreased from 0.71 +/- 0.04 to 0.60 +/- 0.07 under maltodextrin
      only and from 0.73 +/- 0.06 to 0.56 +/- 0.08 under combined treatments. There was
      an increase in biovolume, from 2.5 +/- 1 mm3 to 7 +/- 1 mm3 , under the
      vancomycin-only treatment, while the maltodextrin-only and combined treatments
      showed no significant change in biovolume over time. This indicated that physical
      biofilm growth was halted during maltodextrin-only and combined treatments.

PMID- 29460280
TI  - The protective effects of Sauropus spatulifolius on acute lung injury induced by
      lipopolysaccharide.
AB  - BACKGROUND: Sauropus spatulifolius Beille (named 'Long-Li-Ye' in China) is used
      to make 'herbal tea' to prevent pneumonia. This study aimed to evaluate the
      antioxidant activities in vitro and the protective effects of Long-Li-Ye on acute
      lung injury (ALI) induced by lipopolysaccharide (LPS). RESULTS: The supernatant
      after ethanol addition to Long-Li-Ye water extract (LLYCSL) and the resin eluting
      fraction of LLYCSL (LLY40) showed strong antioxidant activities in vitro. LLYCSL
      and LLY40 could attenuate ALI via decreasing myeloperoxidase activity, increasing
      superoxide dismutase activity and decreasing the levels of tumor necrosis factor
      alpha (TNF-alpha), interleukin 1beta (IL-1beta) and IL-6. In addition, LLY40
      could increase catalase activity, increase the levels of IL-10, IL-4 and IL-13
      and decrease the TNF-alpha/IL-10 ratio. CONCLUSION: Long-Li-Ye could be used as a
      natural antioxidant for food production and functional food or dietary
      supplementation for people with ALI. (c) 2018 Society of Chemical Industry.

PMID- 29460281
TI  - Alexithymia and risk preferences: Predicting risk behaviour across decision
      domains.
AB  - Risk-taking is a critical health factor as it plays a key role in several
      diseases and is related to a number of health risk factors. The aim of the
      present study is to investigate the role of alexithymia in predicting risk
      preferences across decision domains. One hundred and thirteen participants filled
      out an alexithymia scale (Toronto Alexithymia Scale-TAS-20), impulsivity and
      venturesomeness measures (I7 scale), and-1 month later-the Cognitive Appraisal of
      Risky Events (CARE questionnaire). The hierarchical regression analyses showed
      that alexithymia positively predicted risk preferences in two domains:
      aggressive/illegal behaviour and irresponsible academic/work behaviour. The
      results also highlighted a significant association of the alexithymia facet,
      externally oriented thinking (EOT), with risky sexual activities. EOT also
      significantly predicted aggressive/illegal behaviour and irresponsible
      academic/work behaviour. The alexithymia facet, Difficulty Identifying Feelings,
      significantly predicted irresponsible academic/work behaviour. The results of the
      present study provide interesting insights into the connection between
      alexithymia and risk preferences across different decision domains. Implications
      for future studies and applied interventions are discussed.

PMID- 29460283
TI  - Early exercise for lifelong benefit: sustained cardiac programming in rats and
      the potential translation to humans.

PMID- 29460282
TI  - The versatility of the CD1 lipid antigen presentation pathway.
AB  - The family of non-classical major histocompatibility complex (MHC) class-I like
      CD1 molecules has an emerging role in human disease. Group 1 CD1 includes CD1a,
      CD1b and CD1c, which function to display lipids on the cell surface of antigen
      presenting cells for direct recognition by T-cells. The recent advent of CD1
      tetramers and the identification of novel lipid ligands has contributed towards
      the increasing number of CD1-restricted T-cell clones captured. These advances
      have helped to identify novel donor unrestricted and semi-invariant T-cell
      populations in humans and new mechanisms of T-cell recognition. However, although
      there is an opportunity to design broadly acting lipids and harness the
      therapeutic potential of conserved T-cells, knowledge of their role in health and
      disease is lacking. We briefly summarize the current evidence implicating group 1
      CD1 molecules in infection, cancer and autoimmunity and show that although CD1
      are not as diverse as MHC, recent discoveries highlight their versatility as they
      exhibit intricate mechanisms of antigen presentation.

PMID- 29460284
TI  - Dementia and Risk of 30-Day Readmission in Older Adults After Discharge from
      Acute Care Hospitals.
AB  - OBJECTIVES: To assess the association between dementia and risk of hospital
      readmission and to evaluate whether the effect of dementia on hospital
      readmission varies according to primary diagnosis. DESIGN: Retrospective cohort
      study. SETTING: Nationwide discharge database of acute care hospitals in Japan.
      PARTICIPANTS: Individuals aged 65 and older diagnosed with one of the 30 most
      common diagnoses and discharged from 987 hospitals between April 2014 and
      September 2015 (N = 1,834,378). MEASUREMENTS: The primary outcome was unplanned
      hospital readmission within 30 days. Poisson generalized estimating equation
      models were fitted to assess the risks of readmission for individuals with and
      without dementia, using primary diagnosis as a possible effect modifier and
      clinical factors as potential confounders. RESULTS: The overall prevalence of
      dementia was 14.7% and varied according to primary diagnosis, ranging from 3.0%
      in individuals with prostate cancer to 69.4% in those with aspiration pneumonia.
      Overall, individuals with dementia had a higher risk of hospital readmission
      (8.3%) than those without (4.1%) (adjusted risk ratio (aRR])=1.46, 95% confidence
      interval (CI)=1.44-1.49), although diagnostic category substantially modified the
      relationship between dementia and hospital readmission. For hip fracture,
      dementia was associated with greater risk of hospital readmission (adjusted risk
      11.5% vs 7.9%; aRR=1.46; 95% CI=1.28-1.68); this risk was attenuated for
      cholecystitis (adjusted risk 12.8% vs 12.4%; aRR=1.03; 95% CI=0.90-1.18).
      CONCLUSION: Risk of hospital readmission associated with dementia varied
      according to primary diagnosis. Healthcare providers could enforce interventions
      to minimize readmission by focusing on comorbid conditions in individuals with
      dementia and specific primary diagnoses that increase their risk of readmission.

PMID- 29460285
TI  - Antibiotic use questioned.

PMID- 29460286
TI  - RNAi assisted genome evolution unveils yeast mutants with improved xylose
      utilization.
AB  - Xylose is a major component of lignocellulosic biomass, one of the most abundant
      feedstocks for biofuel production. Therefore, efficient and rapid conversion of
      xylose to ethanol is crucial in the viability of lignocellulosic biofuel plants.
      In this study, RNAi Assisted Genome Evolution (RAGE) was used to improve the
      xylose utilization rate in SR8, one of the most efficient publicly available
      xylose utilizing Saccharomyces cerevisiae strains. To identify gene targets for
      further improvement, we created a genome-scale library consisting of both genetic
      over-expression and down-regulation mutations in SR8. Followed by screening in
      media containing xylose as the sole carbon source, yeast mutants with 29% faster
      xylose utilization, and 45% higher ethanol productivity were obtained relative to
      the parent strain. Two known and two new effector genes were identified in these
      mutant strains. Notably, down-regulation of CDC11, an essential gene, resulted in
      faster xylose utilization, and this gene target cannot be identified in genetic
      knock-out screens.

PMID- 29460287
TI  - Chromosomal aberrations and CNVs in twin fetuses with cardiovascular anomalies:
      Comparison between monochorionic diamniotic and dichorionic diamniotic twins.
AB  - OBJECTIVE: To investigate the types of cardiovascular anomalies and the results
      of invasive prenatal diagnosis in twin fetuses. METHODS: A total of 298 fetuses
      in 149 twin pairs were enrolled, in which 1 or 2 fetuses of a twin pair had
      cardiovascular anomalies. Prenatal diagnosis was performed on 290 fetuses of 149
      twin pairs, including 150 monochorionic diamniotic (MCDA) fetuses (79 pairs) and
      140 dichorionic diamniotic (DCDA) fetuses (70 pairs). G-Banding karyotyping
      and/or chromosomal microarray analysis were performed. The types of
      cardiovascular anomalies and the results of prenatal diagnosis were analyzed.
      RESULTS: Fifty percent (79/158) fetuses in MCDA group and 52.1% (73/140) fetuses
      in DCDA group were diagnosed with cardiovascular anomalies by ultrasound. Primary
      cardiac structural defects such as septal defects and tetralogy of Fallot were
      more common in DCDA group than in MCDA group, while acardiac anomaly was the most
      common in MCDA group. Chromosomal aberrations were identified in 7.7% fetuses
      (11/142) of MCDA group and in 18.3% fetuses (22/120) of DCDA group by G-banding
      karyotyping. Except benign copy number variations (CNVs), 37 CNVs (pathogenic,
      likely pathogenic, and variant of uncertain significance) and chromosomal
      aberrations were detected in 21.3% (32/150) fetuses of MCDA group and 47 CNVs
      (pathogenic, likely pathogenic, and variant of uncertain significance) and
      chromosomal aberrations were detected in 32.1% (45/140) fetuses of DCDA group by
      chromosomal microarray analysis. CONCLUSIONS: Most of cardiovascular anomalies
      were identified in one fetus of a twin pair no matter in MCDA or DCDA twin.
      Primary cardiac structural defects were more common in DCDA group. Monozygotic
      twins may have discordant phenotypes, karyotypes, and CNVs between 2 fetuses of
      each pair.

PMID- 29460288
TI  - Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult
      Holstein dairy cows.
AB  - A transdermal formulation of the nonsteroidal anti-inflammatory drug, flunixin
      meglumine, has been approved in the United States and Canada for single-dose
      administration. Transdermal flunixin meglumine was administered to 10 adult
      Holstein cows in their second or third lactation at the label dose of 3.33 mg/kg
      every 24 hr for three total treatments. Plasma flunixin concentrations were
      determined using high-pressure liquid chromatography with mass spectroscopy (HPLC
      MS). Pharmacokinetic analysis was completed on each individual animal with
      noncompartmental methods using computer software. The time to maximum drug
      concentration (Tmax) was 2.81 hr, and the maximum drug concentration was 1.08
      MUg/ml. The mean terminal half-life (T1/2) was determined to be 5.20 hr.
      Clearance per fraction absorbed (Cl/F) was calculated to be 0.294 L/hr kg-1 , and
      volume of distribution of fraction (Vz/F) absorbed was 2.20 L/kg. The mean
      accumulation factor was 1.10 after three doses. This indicates changes in dosing
      may not be required when giving multiple doses of flunixin transdermal. Further
      work is required to investigate the clinical efficacy of transdermal flunixin
      after multiple daily doses.

PMID- 29460289
TI  - Endogenous factors and mechanisms of renoprotection and renal repair.
AB  - BACKGROUND: An imbalance between renal damaging molecules and nephroprotective
      factors contributes to the development and progression of kidney diseases.
      Molecules with renoprotective properties might serve as biomarkers, drug targets
      as well as therapeutic options themselves. MATERIALS AND METHODS: For this
      review, we generated a set of renoprotective factors based on GeneRIF (Gene
      Reference Into Function) information available at NCBI's PubMed. The final set of
      manually curated renoprotective factors was investigated with respect to tissue
      specific expression, subcellular location distribution and involvement in
      biological processes using information from gene ontology as well as information
      from protein-protein interaction databases. We furthermore investigated the
      factors in the context of clinical trials of renal disease and diabetes. RESULTS:
      One hundred and ninety-three factors could be retrieved from the set of GeneRIFs
      on nephroprotection and renal repair. A large number of factors were either
      secretory molecules or plasma membrane receptors. Next to the elevated expression
      in renal tissue, also higher expression in connective tissue and pancreas was
      observed. The proteins could be assigned to the broad functional categories of
      cell proliferation and signalling, inflammatory response, apoptosis, blood
      pressure regulation as well as cellular response to different kinds of insults
      such as hypoxia, heat or mechanical stimulus. Eight factors are studied in
      clinical trials with additional ones being targeted by compounds. CONCLUSIONS: We
      have generated a set of renoprotective factors based on the literature
      information, which was functionally annotated and evaluated with respect to
      tested compounds in kidney disease and diabetes clinical trials.

PMID- 29460290
TI  - Extent of lymph node dissection improves survival in prostate cancer patients
      treated with radical prostatectomy without lymph node invasion.
AB  - PURPOSE: To assess the effect of pelvic lymph node dissection (PLND) extent on
      cancer-specific mortality (CSM) in prostate cancer (PCa) patients without lymph
      node invasion (LNI) treated with radical prostatectomy (RP). METHODS: Within the
      Surveillance, Epidemiology, and End results (SEER) database (2004-2014), we
      identified patients with D'Amico intermediate- or high-risk characteristics who
      underwent RP with PLND, without evidence of LNI. First, multivariable logistic
      regression models tested for predictors of more extensive PLND, defined as
      removed lymph node count (NRN) >=75th percentile. Second, Kaplan-Meier analyses
      and multivariable Cox regression models tested the effect of NRN >=75th
      percentile on CSM. Finally, survival analyses were repeated using continuously
      coded NRN. RESULTS: In 28 147 RP and PLND patients without LNI, 67.3% versus
      32.7% exhibited D'Amico intermediate- or high-risk characteristics. The median
      NRN was 6 (IQR 3-10), the 75th percentile defined patients with NRN >=11.
      Patients with NRN >=11 had higher rate of cT2/3 stage (29.8 vs 26.1%), GS >=8
      (25.7 vs 22.4%), and respectively more frequently exhibited D'Amico high-risk
      characteristics (34.6 vs 32.1%). In multivariable logistic regression models
      predicting the probability of more extensive PLND (NRN >=11), higher biopsy GS,
      higher cT stage, higher PSA, more recent year of diagnosis, and younger age at
      diagnosis represented independent predictors. At 72 months after RP, CSM-free
      rates were 99.5 versus 98.1% for NRN >=11 and NRN <=10, respectively and resulted
      in a HR of 0.50 (P = 0.01), after adjustment for all covariates. Similarly,
      continuously coded NRN achieved independent predictor status (HR: 0.955, P =
      0.01), where each additional removed lymph node reduced CSM risk by 4.5%.
      CONCLUSION: More extensive PLND at RP provides improved staging information and
      consequently is associated with lower CSM in D'Amico intermediate- and high-risk
      PCa patients without evidence of LNI. Hence, more extensive PLND should be
      recommended in such individuals.

PMID- 29460291
TI  - Theoretical study of the effect of piezoelectric bone matrix on transient fluid
      flow in the osteonal lacunocanaliculae.
AB  - A new theoretical generation mechanism of the transient streaming potential
      considering variations in the surface potential on the wall in a
      lacunocanalicular system, is proposed based on the assumption of the
      piezoelectric bone matrix. To obtain the streaming potential analytically, a
      modified transient charge density equation is proposed. An osteon is modeled as a
      piezoelectric solid phase having fluid-filled cavities (lacunae) connected by
      channels (canaliculae) to obtain the pressure gradients in the canaliculae and
      the electric boundary conditions on the canalicular walls. In addition, this
      study focused on modeling of the negatively charged glycocalyx that fills the
      annular fluid space between the osteocytic process and the canalicular wall. It
      is assumed that the annular fluid space of the canaliculi can be represented as a
      two-layer configuration for flow through a gap (between the tips of the
      glycocalyx and the canalicular wall) overlaying the porous glycocalyx. The
      transient streaming potential and bone fluid flow affected by the generated total
      potential are analyzed using the one-dimensional lacunocanalicular fluid path,
      which is surrounded by the piezoelectric bone matrix. A significant increase in
      the streaming potential is predicted for the case with piezoelectricity. The peak
      streaming potential value with the piezoelectricity is found to be up to 58.8%
      greater compared with that without piezoelectricity. The electroviscous effect
      due to the total electric potential gradients on the fluid velocities in the
      canaliculi is negligible. These findings imply that the piezoelectric effect
      caused by deformation of the bone matrix should be considered for prediction of
      the streaming potential in the lacunocanaliculae. (c) 2018 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res.

PMID- 29460293
TI  - Effect of the sexual abstinence period recommended by the World Health
      Organization on clinical outcomes of fresh embryo transfer cycles with normal
      ovarian response after intracytoplasmic sperm injection.
AB  - This study was to investigate whether the sexual abstinence period (SAP)
      recommended by the World Health Organization (WHO) affects clinical outcomes. We
      compared the rate of clinical outcomes between 2-7 and >=8 days of SAP in first
      fresh embryo transfer after intracytoplasmic sperm injection (ICSI) in groups of
      young maternal age (YMA: <38 years) and old maternal age (OMA: >=38 years). We
      conducted a retrospective study of 449 first ICSI cycles with a normal ovarian
      response. SAP was identified before collecting the semen samples. Semen analysis
      was performed based on the guidelines recommended by WHO (2010). Sperm
      preparation was made using the swim-up method. Patients' baseline characteristics
      in the YMA and OMA groups did not differ. The rates of fertilisation, top-quality
      embryos on day 3, biochemical pregnancy, clinical pregnancy, ongoing pregnancy,
      abortion and implantation per cycle were not significantly different between 2-7
      and >=8 days of SAP in the YMA or OMA group. In conclusion, SAP beyond the
      recommended period by WHO was not associated with the rates of a lower
      fertilisation and pregnancy in human in vitro fertilisation (IVF). We think that
      a new criterion of SAP for clinical application in human IVF needs to be
      considered by WHO.

PMID- 29460294
TI  - Varicocelectomy with primary gubernaculum veins closure: A randomised clinical
      trial.
AB  - To evaluate the effect of microsurgical inguinal varicocelectomy with testicular
      delivery on semen parameters. A total of 416 patients, diagnosed with grade III
      varicocele, were randomised into two groups. One group underwent microsurgical
      inguinal varicocelectomy without testicular delivery. For the other group,
      testicular delivery and ligation of gubernacular and all collateral veins were
      performed. A semen analysis was performed before and 6 months after the
      procedure. Mean age of the patients in the case and control groups was 27.3 +/-
      6.1 years and 25.9 +/- 4.6 years respectively (p = .1). The total number of
      recurrence after 6 months in the conventional and testicular delivery groups was
      13 (6.5%) and 3 (1.5%) (p < .05). No case of hydrocele formation was observed in
      any of the groups. All sperm parameters were improved 6 months after the surgery
      in both groups. But comparing the mean improved difference between the two groups
      revealed a significant difference in improvement in sperm motility for patients
      who had undergone varicocelectomy with testicular delivery (p = .05).
      Microsurgical inguinal varicocelectomy is a safe and efficient technique with a
      minimum chance of post-operative complications and recurrence and also may have
      role in improvement of sperm motility compared with conventional techniques.

PMID- 29460295
TI  - Cancer survivorship care plans: Processes, effective strategies, and challenges
      in a Northern Plains rural state.
AB  - OBJECTIVES: Health systems face resource and time barriers to developing and
      implementing cancer survivorship care plans (SCPs) when active cancer treatment
      is completed. To address this problem, the South Dakota (SD) Department of Health
      partnered with two of SD's largest health systems to create the SD Survivorship
      Program. The purpose of this program evaluation study was to describe and compare
      SCP development and implementation at the two health systems. DESIGN & SAMPLE: A
      descriptive qualitative design was used. Interview participants were instrumental
      in the development and implementation of SCPs within their respective health
      system. MEASURES: Content analysis was used to analyze the interview data.
      RESULTS: The two health systems used similar processes for (a) early designation
      of program personnel, (b) developing SCP templates, (c) provider/staff input, and
      (d) identifying/tracking eligible patients. In contrast, they developed differing
      processes for SCP completion and delivery. The two health systems also identified
      effective strategies and challenges in SCP development and implementation.
      CONCLUSION: This evaluation suggests that partnerships between state health
      departments and local health systems could be key for meeting the nation-wide
      goal of universal SCP implementation. Particularly, other low-population rural
      states like SD can use the findings to help build their SCP programs.

PMID- 29460292
TI  - Genetic and environmental (physical fitness and sedentary activity) interaction
      effects on cardiometabolic risk factors in Mexican American children and
      adolescents.
AB  - Knowledge on genetic and environmental (G * E) interaction effects on
      cardiometabolic risk factors (CMRFs) in children is limited.  The purpose of this
      study was to examine the impact of G * E interaction effects on CMRFs in Mexican
      American (MA) children (n = 617, ages 6-17 years). The environments examined were
      sedentary activity (SA), assessed by recalls from "yesterday" (SAy) and "usually"
      (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS). CMRF data
      included body mass index (BMI), waist circumference (WC), fat mass (FM), fasting
      insulin (FI), homeostasis model of assessment-insulin resistance (HOMA-IR), high
      density lipoprotein cholesterol (HDL-C), triglycerides (TG), systolic (SBP) and
      diastolic (DBP) blood pressure, and number of metabolic syndrome components
      (MSC). We examined potential G * E interaction in the phenotypic expression of
      CMRFs using variance component models and likelihood-based statistical inference.
      Significant G * SA interactions were identified for six CMRFs: BMI, WC, FI, HOMA
      IR, MSC, and HDL, and significant G * HPFS interactions were observed for four
      CMRFs: BMI, WC, FM, and HOMA-IR. However, after correcting for multiple
      hypothesis testing, only WC * SAy, FM * SAy, and FI * SAu interactions became
      marginally significant. After correcting for multiple testing, most of CMRFs
      exhibited significant G * E interactions (Reduced G * E model vs. Constrained
      model). These findings provide evidence that genetic factors interact with SA and
      PF to influence variation in CMRFs, and underscore the need for better
      understanding of these relationships to develop strategies and interventions to
      effectively reduce or prevent cardiometabolic risk in children.

PMID- 29460297
TI  - Excess amyloid beta can be degraded in healthy humans.

PMID- 29460296
TI  - An exploratory analysis of the influence of personality and emotional factors on
      cerebral blood flow responses during painful stimulation in Fibromyalgia.
AB  - This study explored the influence of certain personality traits (neuroticism,
      extraversion, psychoticism, alexithymia), emotional variables (depression,
      catastrophizing), and insomnia on cerebral blood flow (CBF) responses to painful
      stimulation in fibromyalgia, using functional transcranial Doppler sonography.
      CBF velocities were recorded bilaterally in the anterior cerebral arteries (ACA)
      and middle cerebral arteries (MCA) of 24 fibromyalgia patients during exposure to
      two painful pressure conditions: (1) fixed pressure (2.4 kg) and (2) an
      individually calibrated pressure to produce an equal-moderate subjective pain
      intensity in all participants (average, 3.5 kg). Psychological factors were
      assessed by means of questionnaires. Neuroticism, and the externally-oriented
      thinking dimension of alexithymia were positively, and extraversion was
      inversely, associated with specific components of ACA and MCA CBF responses.
      Regarding catastrophizing and depression, correlations were positive for the
      fixed pressure condition and negative for the equal subjective intensity
      condition. The findings suggest that alterations in central nervous pain
      processing in fibromyalgia vary according to psychological factors. While most of
      the observed associations reflect a linear increase in nociceptive processing
      with the magnitude of negative cognitive and emotional states, the inverse
      associations for catastrophizing and depression during more intense painful
      stimulation may be ascribed to anti-nociceptive effects due to activation of the
      defense reflex.

PMID- 29460298
TI  - Inverse association of insulin antibody levels with insulin sensitivity in adults
      with Type 1 diabetes.
AB  - AIMS: Insulin resistance may contribute to the pathogenesis of autoimmune
      mediated diabetes. Antibodies against beta-cell-associated molecules, comprising
      islet cell antigen (ICA), glutamic acid decarboxylase (GAD) and insulin,
      characterize the autoimmune process. Because the link between insulin resistance
      and autoimmunity might be relevant for disease progression and treatment, we
      hypothesized that insulin resistance associates positively with beta-cell
      directed antibodies in newly diagnosed Type 1 diabetes. METHODS: Within the
      German Diabetes Study, an observational study including adults with newly
      diagnosed diabetes, 142 adults [84 men, 58 women; age 33.1 (26.4, 41.9) years;
      diabetes duration 6.3 (4.2, 9.1) months] positive for at least one antibody
      against ICA, GAD or insulin underwent hyperinsulinaemic-euglycaemic clamp tests
      to assess insulin sensitivity (M-value) in a cross-sectional setting. RESULTS:
      Insulin-directed antibodies were inversely correlated with M-values (beta = 
      0.039). Albeit not strong, the association persisted after adjustment for age,
      sex and BMI, and even after further adjustment for confounders reflecting
      exposure to exogenous insulin and residual beta-cell secretory capacity.
      Correlation network-based analyses revealed a complex interaction between levels
      of fasting insulin and of insulin antibodies with respect to their relationship
      with the M-value. GAD- or ICA-directed antibodies did not correlate with insulin
      sensitivity. CONCLUSIONS: In adults with recent-onset Type 1 diabetes expressing
      at least one beta-cell-directed antibody, insulin sensitivity is inversely
      related to insulin antibody titres, but not to other autoantibodies. Our finding
      may allow for the identification of insulin resistance in adults with high levels
      of insulin antibodies.

PMID- 29460299
TI  - Postnatal depression in a community-based study of women with polycystic ovary
      syndrome.
AB  - INTRODUCTION: Women with polycystic ovary syndrome are susceptible to depression
      and anxiety and so may also be at risk for postnatal depression. This study
      investigates whether women with polycystic ovary syndrome have an elevated risk
      of postnatal depression. MATERIAL AND METHODS: Cross-sectional data for parous
      women (n = 566) were available from a birth cohort. Polycystic ovary syndrome was
      diagnosed using the Rotterdam criteria. Details of reproductive history,
      pregnancy, birth, and postnatal depression were obtained through structured
      interview. Comparisons were made between women with and without polycystic ovary
      syndrome using logistic regression analysis, including the investigation of
      interactions. RESULTS: A positive but statistically non-significant association
      was found between polycystic ovary syndrome and postnatal depression (odds ratio
      1.6, 95% confidence interval 0.9-2.9). Compared with their counterparts, women
      with polycystic ovary syndrome were substantially more likely: to have difficulty
      conceiving (odds ratio 5.2, 95% confidence interval 2.9-9.4), to have conceived
      with medical assistance (odds ratio 11.6, 95% confidence interval 5.5-24.4), and
      to have pregnancy complications (gestational diabetes, pregnancy-induced
      hypertension, or preeclampsia; odds ratio 2.0, 95% confidence interval 1.1-3.5).
      Where women with polycystic ovary syndrome had a history of miscarriage or
      conceived with medical assistance, the combination interacted (p = 0.06 and p <
      0.05, respectively), with over half of such women having postnatal depression.
      CONCLUSIONS: Although women with polycystic ovary syndrome may not have an excess
      risk of postnatal depression overall, those who had suffered a miscarriage or
      required medical assistance to conceive were at substantially elevated risk.
      Findings point to vulnerability inherent in polycystic ovary syndrome being
      amplified, either by stressful experiences on the pathway to pregnancy/childbirth
      or by specific fertility treatment regimens.

PMID- 29460300
TI  - Catheter-associated venous air embolism in hospitalized horses: 32 cases.
AB  - BACKGROUND: Venous air embolism is a potentially life-threatening complication of
      IV catheter use in horses. Despite widespread anecdotal reports of their
      occurrence, few cases have been reported in the literature and the prognosis is
      currently unknown. HYPOTHESIS/OBJECTIVES: Our objective was to describe the
      surrounding circumstances, clinical signs, treatment, progression, and outcome of
      venous air embolism in hospitalized horses. ANIMALS: Thirty-two horses with acute
      onset of compatible clinical signs associated with IV catheter disconnection or
      damage. METHODS: Multicenter retrospective study. Data extracted from clinical
      records included signalment, presenting complaint, catheter details, clinical
      signs, treatments, and outcome. RESULTS: Most cases resulted from extension set
      disconnection occurring within approximately 24 hours after catheter placement.
      In fewer horses, extension set damage was cited as a cause. Common clinical signs
      included tachycardia, tachypnea, recumbency, muscle fasciculations and agitation,
      with abnormal behavior including kicking and flank biting. Less commonly,
      pathological arrhythmias or more severe neurologic signs, including blindness and
      seizures, were noted. Progression was unpredictable, with some affected horses
      developing delayed-onset neurologic signs. Mortality was 6/32 (19%), including 2
      cases of sudden death and other horses euthanized because of persistent
      neurologic deficits. Negative outcomes were more common in horses with recorded
      blindness, sweating or recumbency, but blindness resolved in 5/8 affected horses.
      CONCLUSIONS AND CLINICAL IMPORTANCE: The prognosis for resolution of clinical
      signs after air embolism is fair, but permanent neurologic deficits or pathologic
      cardiac arrhythmias can arise. Unpredictable progression warrants close
      monitoring. Systematic clinic-based surveillance could provide additional useful
      information to aid prevention.

PMID- 29460301
TI  - Cardiac perforation 6 years following the implantation of an Amplatzer septal
      occluder.

PMID- 29460302
TI  - Fecal microbiota transplantation in puppies with canine parvovirus infection.
AB  - BACKGROUND: Diarrhea associated with parvovirus infection is common in dogs.
      Supportive care is the mainstay of treatment, but recovery may be prolonged and
      mortality rate can be high. Modification of the intestinal bacterial microbiota
      has been promising in human and veterinary medicine as an adjunctive treatment of
      various enteric diseases. OBJECTIVES: To investigate the safety and efficacy of
      fecal microbiota transplantation (FMT) on the clinical recovery of puppies with
      acute hemorrhagic diarrhea syndrome. ANIMALS: Sixty-six puppies with parvovirus
      infection were evaluated at 2 veterinary hospitals. METHODS: Randomized clinical
      trial. Puppies were randomly distributed into 2 groups: standard treatment (STD)
      and standard treatment + FMT (STD + FMT). The STD puppies (n = 33) received only
      treatment with IV fluids and antimicrobials and the STD + FMT puppies (n = 33)
      received FMT in addition to standard treatment. For FMT, 10 g of feces from a
      healthy dog diluted in 10 mL of saline were administered rectally 6-12 hours post
      admission. RESULTS: Among survivors, treatment with FMT was associated with
      faster resolution of diarrhea (P < .001) and shorter hospitalization time (P =
      .001; median, 3 days in STD + FMT; median, 6 days in STD) compared to standard
      treatment. Mortality in STD was 36.4% (12/33) as compared to 21.2% (7/33) in
      puppies treated with FMT, but there was no statistical difference between groups
      (P = .174). Polymerase chain reaction indicated that all animals carried canine
      parvovirus, strain CPV-2b. CONCLUSIONS: Fecal microbiota transplantation in
      parvovirus-infected puppies was associated with faster resolution of diarrhea.

PMID- 29460303
TI  - Polycystic ovary syndrome and adverse pregnancy outcomes: Current state of
      knowledge, challenges and potential implications for practice.
AB  - Although there is a growing body of literature reporting that pregnancies in
      women with polycystic ovary syndrome (PCOS) are associated with greater
      complications than those without PCOS, methodological differences across studies
      make these results difficult to consolidate. This narrative review outlines
      potential mechanisms involved in adverse pregnancy outcomes in PCOS and the
      nature of the complications. It covers limitations of current evidence and future
      research directions. Future research should include prospective studies with
      phenotypic stratification of PCOS and matching or consideration of specific PCOS
      manifestations and risk factors specific to each pregnancy complication. This
      review also emphasizes the importance of following a healthy lifestyle for women
      with PCOS and of individualized care according to overall risk factors for
      pregnancy complications.

PMID- 29460304
TI  - Sperm retrieval by microdissection testicular sperm extraction and
      intracytoplasmic sperm injection outcomes in nonobstructive azoospermic patients
      with Klinefelter syndrome.
AB  - Klinefelter syndrome is the most frequent chromosomal abnormality in patients
      with nonobstructive azoospermia. The development of advanced assisted
      reproductive techniques, such as testicular sperm extraction and intracytoplasmic
      sperm injection, has provided the possibility of biological fathering in
      nonobstructive azoospermic patients with Klinefelter syndrome. We aimed to
      evaluate our sperm retrieval rate by microdissection testicular sperm extraction
      and to analyse the intracytoplasmic sperm injection outcomes in these patients.
      Medical records of 110 nonobstructive azoospermic patients with Klinefelter
      syndrome were retrospectively reviewed. We found that the sperm retrieval rate by
      microdissection testicular sperm extraction is lower than published reports on
      other types of secretory azoospermia. The statistical analyses yielded that age,
      FSH and testosterone levels as predictive factors for successful sperm retrieval.

PMID- 29460305
TI  - Photochemical inhibition of Trichophyton rubrum by different compoundings of
      curcumin.
AB  - Recently, we had shown that conidia-derived growth of many dermatophytes can be
      inhibited by curcumin plus exposure to visible light. This method of photo
      inactivation should be developed further aiming for an option to stop mycelial
      growth in superficial tinea. Wells of microtitre plates were inoculated with
      either mycelial or conidial elements collected from 5 strains of Trichophyton
      rubrum. Then either micellar curcumin or curcumin dissolved with DMSO was added
      and after 20 min the wells were filled up with Sabouraud broth. Thereafter the
      assays were irradiated once with visible light (wave length 420 nm, 20 J/cm2 )
      and fungal growth was monitored photometrically. Identical effects were measured
      with conidia and mycelial elements of all 5 T. rubrum strains. Curcumin dissolved
      with DMSO plus irradiation had a marked dose-dependent inhibitory effect on
      fungal growth that was almost complete with 5.0 mg/L (P < .01) over a period of 9
      days. In contrast, the same procedure with micellar curcumin had no inhibitory
      effect on growth obtained from conidia or mycelial elements. Mycelial elements of
      T. rubrum and its conidia are equally sensitive to photochemical inactivation
      with curcumin and the galenic compounding of curcumin is essential to achieve
      this photochemical effect.

PMID- 29460306
TI  - Pathophysiology of axial spondyloarthritis: Consensus and controversies.
AB  - BACKGROUND: Axial spondyloarthritis (axSpA) is a common inflammatory arthritis of
      the sacroiliac joints and the spine. The best-known and most studied form of
      axSpA is ankylosing spondylitis. DESIGN: In this review, we provide a brief
      overview of the pathophysiology of axSpA. In addition, we performed a
      quantitative text analysis of reviews on the pathogenesis of axSpA published in
      the last 10 years to establish the current consensus in various fields of
      research into the pathogenesis of axSpA. RESULTS: There appears to be broad
      consensus on genetic risk factors and the involvement of the immune system in the
      initiation phase of the disease although little consensus was found on which
      specific immune cells drive disease. Moreover, despite relatively little data
      available, alterations in the microbiome are commonly thought to be involved in
      disease. Abnormal bone formation is the most prominent pathogenic factor thought
      to be involved in disease progression. CONCLUSION: So, although the
      pathophysiology of axSpA remains incompletely understood, the progress in recent
      years in several fields of research in axSpA including genetics, diagnosis,
      imaging and therapeutics, hold great promise for the future.

PMID- 29460307
TI  - Antibodies to human platelet antigens form a significant proportion of platelet
      antibodies detected in Indian patients with refractoriness to platelet
      transfusions.
AB  - BACKGROUND: The transfusion of platelets is an important therapeutic strategy in
      bleeding patients with thrombocytopenia. However, some chronically transfused
      patients fail to achieve the appropriate platelet count increment following
      transfusion due to the presence of platelet alloantibodies. OBJECTIVES: The aims
      of this research were to study the prevalence of platelet alloimmunisation and to
      characterise the platelet-reactive (PR) antibodies in haematology patients
      refractory to platelet transfusions in an Indian setting. PATIENTS AND METHODS: A
      total of 80 patients with a prior history of multiple transfusions (minimum of
      five cellular transfusions) were included in the study if they did not achieve an
      adequate corrected count increment within 24 h of the platelet transfusion.
      Patients with non-immunological causes of platelet refractoriness were excluded
      from the study. The test was performed on a blood sample of 4 mL of
      Ethylenediaminetetraacetic acid (EDTA) blood sample in which plasma was separated
      and stored at -80  degrees C and underwent batch testing in PAK-2LE. RESULTS: The
      overall prevalence of platelet alloimmunisation in our study was 60%. Of the 48
      patients who were detected to have platelet antibodies, the combination of anti
      human leucocyte antigen (HLA) and platelet-specific (PS) antibodies together
      constituted the majority of 54.2%. The overall prevalence of anti-HLA antibodies
      was 51.25% and of PS antibodies was 41.25% in the total study population of 80.
      CONCLUSION: The overall prevalence of PS antibodies in our study was greater than
      that reported by other groups in India and other countries. This needs to be
      considered, particularly in the management of patients refractory to platelet
      transfusions, where HLA-matched platelets constitute current best practice.

PMID- 29460308
TI  - Parental Depression, Overreactive Parenting, and Early Childhood Externalizing
      Problems: Moderation by Social Support.
AB  - This study used a large (N = 519), longitudinal sample of adoptive families to
      test overreactive parenting as a mediator of associations between parental
      depressive symptoms and early childhood externalizing, and parents' social
      support satisfaction as a moderator. Maternal parenting (18 months) mediated the
      association between maternal depressive symptoms (9 months) and child
      externalizing problems (27 months). Paternal parenting was not a significant
      mediator. Unexpectedly, we found a cross-over effect for the moderating role of
      social support satisfaction, such that partners' social support satisfaction
      reduced the strength of the association between each parent's own depressive
      symptoms and overreactive parenting. Results point to the importance of
      accounting for broader family context in predicting early childhood parenting and
      child outcomes.

PMID- 29460309
TI  - Entrapment of LTB protein in alginate nanoparticles protects against
      Enterotoxigenic Escherichia coli.
AB  - Vaccine delivery vehicles are just as important in vaccine efficiency. Through
      the progress in nanotechnology, various nanoparticles have been evaluated as
      carriers for these substances. Among them, alginate nanoparticles are a good
      choice because of their biodegradability, biocompatibility, ease of production,
      etc. In this study, feasibility of alginate nanoparticles (NPs) such as
      recombinant LTB from Enterotoxigenic Escherichia coli (ETEC) carrier was
      investigated. To do this, the eltb gene was cloned and expressed in E. coli BL21
      (DE3) host cells, and a Ni-NTA column purified the protein. NPs were achieved
      through ion gelation method in the presence of LTB protein and CaCl2 as the cross
      Linker and NPs were characterized physicochemically. Balb/C mice groups were
      immunized with LTB-entrapped NPs or LTB with adjuvant and immunogenicity was
      assessed by evaluating IgG titer. Finally, the neutralization of antibodies was
      evaluated by GM1 binding and loop assays. LTB protein was expressed and
      efficiently entrapped into the alginate NPs. The size of NPs was less than 50 nm,
      and entrapment efficiency was 80%. Western blotting showed maintenance of the
      molecular weight and antigenicity of the released protein from NPs.
      Administration of LTB-entrapped NPs stimulated antibody responses in immunized
      mice. Immunization induced protection against LT toxin of ETEC in ileal loops and
      inhibits enterotoxin binding to GM1-gangliosides. Alginate NPs are also
      appropriate vehicle for antigen delivery purpose. Moreover because of their
      astonishing properties, they have the potential to serve as an adjuvant.

PMID- 29460310
TI  - LC-MS based metabolic and metabonomic studies of Panax ginseng.
AB  - INTRODUCTION: Panax ginseng has received much attention as a valuable health
      supplement with medicinal potential. Its chemical diversity and multiple
      pharmacological properties call for comprehensive methods to better understand
      the effects of ginseng and ginsenosides. Liquid chromatography-mass spectrometry
      (LC-MS) based metabonomic approaches just fit the purpose. OBJECTIVE: Aims to
      give a review of recent progress on LC-MS based pharmacokinetic, metabolic, and
      phytochemical metabolomic studies of ginseng, and metabonomic studies of ginseng
      intervention effects. METHODS: The review has four sections: the first section
      discusses metabolic studies of ginsenosides based on LC-MS, the second focuses on
      ginsenoside-drug interactions and pharmacokinetic interaction between herb
      compounds based on LC-MS, the third is phytochemical metabolomic studies of
      ginseng based on LC-MS, and the fourth deals with metabonomic studies of ginseng
      intervention effects based on LC-MS. RESULTS: LC-MS based metabonomic research on
      ginseng include analysis of single ginsenoside and total ginsenosides. The theory
      of multi-components and multi-targeted mechanisms helps to explain ginseng
      effects. CONCLUSION: LC-MS based metabonomics is a promising way to
      comprehensively assess ginseng. It is valuable for quality control and mechanism
      studies of ginseng.

PMID- 29460311
TI  - Enhancing cytochrome P450-mediated non-natural cyclopropanation by mutation of a
      conserved second-shell residue.
AB  - Engineered cytochrome P450s are emerging as powerful synthetic tools due to their
      ability catalyze non-native metallocarbenoid and -nitrenoid insertion reactions.
      P450-mediated cyclopropanation has garnered particular interest due to the high
      selectivity demonstrated by engineered scaffolds and their application towards
      the synthesis of therapeutic agents. We previously reported that mutation of a
      conserved, first-shell heme-ligating Cys to Ser led to significant improvements
      in cyclopropanation activity in a model enzyme, P450BM3h . Here, we demonstrate
      that mutation of a ubiquitously conserved second-shell Phe (F393) to His or Ala,
      provides complementary increases in the P450 heme reduction potential and
      conversion to cyclopropanation products when compared to first-shell Cys to Ser
      mutations. Furthermore, we show that these mutations confer improved non-natural
      catalysis in 4 diverse P450 scaffolds.

PMID- 29460312
TI  - Eigenstate versus Zeeman-based approaches to the solid effect.
AB  - The solid effect is one of the simplest and most effective mechanisms for dynamic
      nuclear polarization. It involves the exchange of polarization between one
      electron and one nuclear spin coupled via the hyperfine interaction. Even for
      such a small spin system, the theoretical understanding is complicated by the
      contact with the lattice and the microwave irradiation. Both being weak, they can
      be treated within perturbation theory. In this work, we analyze the two most
      popular perturbation schemes: the Zeeman and the eigenstate-based approaches,
      which differ in the way the hyperfine interaction is treated. For both schemes,
      we derive from first principles an effective Liouville equation that describes
      the density matrix of the spin system; we then study numerically the behavior of
      the nuclear polarization for several values of the hyperfine coupling. In
      general, we obtain that the Zeeman-based approach underestimates the value of the
      nuclear polarization. By performing a projection onto the diagonal part of the
      spin-system density matrix, we are able to understand the origin of the
      discrepancy, which is due to the presence of parasite leakage transitions
      appearing whenever the Zeeman basis is employed.

PMID- 29460313
TI  - Response to queries on the use of urine dipstick tests for infants with
      unexplained fever.

PMID- 29460314
TI  - Brooding as moderator of depressive symptoms after a work accident: A
      longitudinal study.
AB  - This study analyzes the relationship between having experienced a work accident
      and developing depressive symptoms six months later, considering the subjective
      severity of accidents, the use of both positive and negative religious coping
      strategies, and brooding as predictors variables. Fifty seven women and 187 men
      were evaluated during the month following their accident (T1) and six months
      later (T2). The results show that after controlling for initial depressive
      symptoms, all predictors showed a statistically significant relationship with
      depression at six months, including the interaction between brooding and
      subjective severity of accident. Forty nine percent of resilient participants
      exhibited low symptoms at T1 and T2, 22% of recovered individuals showed high
      symptoms at T1 and low symptoms afterwards, 20% of depressive individuals had
      high symptoms at T1 and T2, and 8% exhibited high symptoms only at T2. High
      severity, brooding and religious coping at T1 differentiated those who exhibited
      stable symptoms from those who were resilient. Resilience was specifically
      predicted with a negative coefficient by the interaction of brooding with
      subjective severity of accident. We conclude that brooding is a variable that
      moderates the relationship between subjective severity of accident and the
      development and maintenance of depressive symptoms. Subjective severity of
      accident, brooding and negative religious coping are risk factors, while positive
      religious coping is not a sufficient protection factor.

PMID- 29460315
TI  - Sealed osteons in animals and humans: low prevalence and lack of relationship
      with age.
AB  - Sealed osteons are unusual variants of secondary osteons that have received
      little attention, especially in non-human bones. Sealed osteons are characterized
      by central canals that are plugged with bone tissue. As with other variants of
      secondary osteons (e.g. drifting, dumbbell, multi-canal), understanding how and
      why sealed osteons form can shed light on the mechanisms that regulate normal
      bone remodeling and how this process can be perturbed with aging and some
      diseases. In a recent microscopic evaluation of human tibiae obtained after
      traumatic amputations, 4-5% of the osteons were sealed. It is suggested that this
      high prevalence reflects occasional localized microscopic ischemia from normal
      osteonal remodeling; hence sealed osteons are implicated in human skeletal
      fragility. Therefore, osteon prevalence would be expected to correlate with the
      bone remodeling seen with aging; for example, showing positive relationships
      between sealed osteons and the population density of typical secondary osteons
      (OPD). We evaluated the prevalence of partially sealed (80-99% sealed) and fully
      sealed osteons with respect to age and variations in OPD in 10 adult human femora
      (34-71 years) and in various non-human appendicular bones of mature animals that
      were not of advanced age, including deer calcanei, equine radii and equine third
      metacarpals. An additional sample of 10 bilateral human femora with unilateral
      non-cemented total hip replacements (F,+HR) and non-implanted contralateral
      femora (F,-HR) were evaluated (10 patients; 52-94 years). In non-human bones,
      sealed + partially sealed osteons were rare (~0.1%) even when having relatively
      high OPD. When considering sealed + partially sealed osteons in femora from
      patients without any HR, results showed that 1.6% of the osteons were sealed or
      partially sealed, which was much lower than anticipated, but this is 10- to 20
      fold more than in any of the non-human bones. Additionally, in all bones, sealed
      + partially sealed osteons were significantly smaller than typical secondary
      osteons (mean diameters: 125 vs. 272 MUm; P < 0.005). In the patients with HR,
      the percentage of sealed + partially sealed osteons: (i) did not correlate with
      age, (ii) showed no significant difference between F,-HR and F,+HR (1.9 vs. 2.1%;
      P = 0.2), and (iii) was positively correlated with OPD (r = 0.67, P = 0.001),
      which differs from the very weak or lack of correlations in the non-human bones
      and the other human femur sample. The lack of an age-related relationship, in
      addition to the very low prevalence of sealed + partially sealed osteons are
      inconsistent with the idea that they contribute to reduced bone quality seen in
      aging humans. The small size of sealed and partially sealed osteons, regardless
      of species affiliation, suggests that they represent closing cones at the termini
      of some osteons. Available evidence suggests that osteons of primates might have
      a greater capacity for branching that is associated with closing cones, which
      might explain the 10-20 times higher prevalence of sealed + partially sealed
      osteons in the human bones examined in this study.

PMID- 29460316
TI  - Light and scanning electron microscopy of the olfactory mucosa in the rufous
      sengi (Elephantulus rufescens).
AB  - Sengis are eutherian insectivores belonging to superorder Afrotheria, a recently
      defined clade of mammals that diverged from other placentals over 100 million
      years ago. In this study, a histological and ultrastructural analysis was carried
      out on the olfactory mucosa (OM) of the rufous sengi (Elephantulus rufescens) and
      the data were compared with those reported earlier in the dog (Canis familiaris)
      and the sheep (Ovis aries), whose dietary lifestyles are carnivorous and
      herbivorous, respectively. Qualitatively, the microstructure of the sengi's OM
      was basically similar to that of the other eutherian mammals except for
      differences in the pattern of cilia projection from the dendritic knobs of the
      olfactory receptor neurons (ORNs) and distribution of Bowman's glands within the
      lamina propria of the OM. On morphometry, significant differences (p < .05) were
      recorded with respect to olfactory epithelial (OE) thickness between the sengi
      (65.4 +/- 2.6 MUm) and the other species. ORN packing density and cilia
      number/ORN knob varied markedly only between the sengi (73.8 +/- 5.4 mm-2  * 103
      and 15 +/- 4, respectively) and the sheep. No remarkable differences were noted
      in regard to ORN bundle diameters between sengis (62.7 +/- 12.5 MUm) and the
      other species. The observed differences in OM structural refinement may be
      attributed to olfactory function demand levels related to feeding lifestyles and
      ecology. Myrmecophagous insectivory, social monogamy, absentee maternal care and
      exposed sheltering habits are behavioural features that may warrant substantial
      OM modification in sengis.

PMID- 29460317
TI  - Effects of aldehyde products of lipid oxidation on the color stability and
      metmyoglobin reducing ability of bovine Longissimus muscle.
AB  - Lipid oxidation and metmyoglobin (MMb) reduction are popular issues in meat color
      research. This study evaluated the effects of aldehyde products, particularly 4
      hydroxy-2-nonenal (HNE) and hexenal, of lipid oxidation on the oxymyoglobin
      stability, mitochondrial membrane permeability, MMb reduction ability, electron
      transport chain-mediated MMb reduction, and nicotinamide adenine dinucleotide
      reduced form (NADH)-dependent MMb reductase activity of bovine Longissimus
      muscle. The results indicated that HNE and hexenal accelerate the oxidation rate
      of oxymyoglobin, significantly increase the permeability of the mitochondrial
      membrane, and inhibit electron transport chain-mediated MMb reduction. However,
      HNE and hexenal were found to exert no effect on the activity of NADH-dependent
      MMb reductase. Thus, the aldehyde products of lipid oxidation could damage the
      microstructure of mitochondria and inhibit mitochondria-mediated MMb reduction,
      which is disadvantageous in terms of the color stability of fresh bovine
      Longissimus muscle.

PMID- 29460318
TI  - Antagonistic effects of growing season and autumn temperatures on the timing of
      leaf coloration in winter deciduous trees.
AB  - Autumn phenology remains a relatively neglected aspect in climate change
      research, which hinders an accurate assessment of the global carbon cycle and its
      sensitivity to climate change. Leaf coloration, a key indicator of the growing
      season end, is thought to be triggered mainly by high or low temperature and
      drought. However, how the control of leaf coloration is split between temperature
      and drought is not known for many species. Moreover, whether growing season and
      autumn temperatures interact in influencing the timing of leaf coloration is not
      clear. Here, we revealed major climate drivers of leaf coloration dates and their
      interactions using 154 phenological datasets for four winter deciduous tree
      species at 89 stations, and the corresponding daily mean/minimum air temperature
      and precipitation data across China's temperate zone from 1981 to 2012. Results
      show that temperature is more decisive than drought in causing leaf coloration,
      and the growing season mean temperature plays a more important role than the
      autumn mean minimum temperature. Higher growing season temperature and lower
      autumn minimum temperature would induce earlier leaf coloration date. Moreover,
      the mean temperature over the growing season correlates positively with the
      autumn minimum temperature. This implies that growing season mean temperature may
      offset the requirement of autumn minimum temperature in triggering leaf
      coloration. Our findings deepen the understanding of leaf coloration mechanisms
      in winter deciduous trees and suggest that leaf life-span control depended on
      growing season mean temperature and autumn low temperature control and their
      interaction are major environmental cues. In the context of climate change,
      whether leaf coloration date advances or is delayed may depend on intensity of
      the offset effect of growing season temperature on autumn low temperature.

PMID- 29460319
TI  - Validity of activity trackers, smartphones, and phone applications to measure
      steps in various walking conditions.
AB  - To examine the validity of popular smartphone accelerometer applications and a
      consumer activity wristband compared to a widely used research accelerometer
      while assessing the impact of the phone's position on the accuracy of step
      detection. Twenty volunteers from 2 different age groups (Group A: 18-25 years, n
      = 10; Group B 45-70 years, n = 10) were equipped with 3 iPhone SE smartphones
      (placed in pants pocket, shoulder bag, and backpack), 1 Samsung Galaxy S6 Edge
      (pants pocket), 1 Garmin Vivofit 2 wristband, and 2 ActiGraph wGTX+ devices (worn
      at wrist and hip) while walking on a treadmill (1.6, 3.2, 4.8, and 6.0 km/h) and
      completing a walking course. All smartphones included 6 accelerometer
      applications. Video observation was used as gold standard. Validity was evaluated
      by comparing each device with the gold standard using mean absolute percentage
      errors (MAPE). The MAPE of the iPhone SE (all positions) and the Garmin Vivofit
      was small (<3) for treadmill walking >=3.2 km/h and for free walking. The Samsung
      Galaxy and hip-worn ActiGraph showed small MAPE only for treadmill walking at 4.8
      and 6.0 km/h and for free walking. The wrist-worn ActiGraph showed high MAPE (17
      47) for all walking conditions. The iPhone SE and the Garmin Vivofit 2 are
      accurate tools for step counting in different age groups and during various
      walking conditions, even during slow walking. The phone's position does not
      impact the accuracy of step detection, which substantially improves the
      versatility for physical activity assessment in clinical and research settings.

PMID- 29460320
TI  - Assessment of quality performance measures in patients with acute coronary
      syndromes: Data from the Portuguese Registry of Acute Coronary Syndromes
      (ProACS), a nationwide registry.
AB  - RATIONAL, AIMS, AND OBJECTIVES: Registries are a powerful tool to assess specific
      performance measurements and quality of care in acute coronary syndromes (ACSs).
      In Portugal, ProACS is a nationwide registry of ACS that has been active for the
      past 15 years, and our objective was to assess specific quality indicators for
      the treatment of ACS. METHODS: Descriptive analysis of data from ProACS registry
      in specific quality indicators previously defined by international scientific
      societies. RESULTS: A total of 45,141 patients were included since 2002, 43.5%
      with ST-segment elevation myocardial infarction. In ST-segment elevation
      myocardial infarction, reperfusion rates, particularly by primary angioplasty,
      have increased dramatically with 85% being submitted to any form of reperfusion
      presently. In-hospital time delays are, however, suboptimal, particularly in
      patients admitted first to hospitals without catheterization facilities. For non
      ST elevation ACS, invasive strategy also showed important improvements, with more
      than 80% of patients being submitted to catheterization. Although there was also
      improvement in the use of guideline recommended medication, particularly statins,
      it is also suboptimal, requiring additional specific interventions. CONCLUSION:
      The quality of care of ACS improved dramatically in the last 15 years in
      Portugal, with major improvements in hospital mortality. It is, however,
      suboptimal in specific points that have been identified and that require
      additional measures.

PMID- 29460321
TI  - Factors associated with delayed infant immunization in a nationally
      representative cohort study.
AB  - BACKGROUND: Many children in developed countries do not receive recommended
      vaccines on time. However, knowledge about factors related to timeliness remains
      limited. Quantifying the relative impact of parental attitudes compared with
      socio-demographic factors for delayed immunization would inform policy responses.
      METHODS: Participants in the nationally representative Longitudinal Study of
      Australian Children were matched with their vaccination histories in the
      Australian Childhood Immunisation Register (N = 4,121). Information about the
      children and their families were collected in face-to-face interviews in 2003
      2004. We considered whether children had completed the primary course for each
      recommended antigen due by 6 months old. Children were categorized as either
      fully immunized, delayed, or totally non-immunized. The outcome was examined
      using logistic regression. Population attributable fractions were estimated for
      key predictors. RESULTS: Delayed immunization was significantly associated with
      indicators of social disadvantage as well as parental disagreement with
      immunization. Attributable fractions for delayed immunization included lone
      motherhood (3.8%; 95% confidence interval CI [0.8, 6.7]), larger family size
      (39.5%; 95% CI [31.2, 46.8]), residential mobility (3.3%; 95% CI [0.1, 6.5]),
      lack of private hospital insurance (9.4%; 95% CI [0.7, 17.3]), a medical
      condition in the child (2.0%; 95% CI [0.2, 3.9]), and parental disagreement with
      immunization (2.1%; 95% CI [0.3, 3.9]). CONCLUSIONS: Parental attitudes accounted
      for a relatively small percentage of delayed infant immunization. In contrast,
      many children who did not receive vaccines on time were characterized by social
      disadvantage, especially larger family size. Researchers and policy-makers should
      consider how to make timely immunization easier for busy parents.

PMID- 29460322
TI  - Amide Neighbouring-Group Effects in Peptides: Phenylalanine as Relay Amino Acid
      in Long-Distance Electron Transfer.
AB  - In nature, proteins serve as media for long-distance electron transfer (ET) to
      carry out redox reactions in distant compartments. This ET occurs either by a
      single-step superexchange or through a multi-step charge hopping process, which
      uses side chains of amino acids as stepping stones. In this study we demonstrate
      that Phe can act as a relay amino acid for long-distance electron hole transfer
      through peptides. The considerably increased susceptibility of the aromatic ring
      to oxidation is caused by the lone pairs of neighbouring amide carbonyl groups,
      which stabilise the Phe radical cation. This neighbouring-amide-group effect
      helps improve understanding of the mechanism of extracellular electron transfer
      through conductive protein filaments (pili) of anaerobic bacteria during mineral
      respiration.

PMID- 29460323
TI  - Clinical guidelines for prevention and management of preterm birth: a systematic
      review.
AB  - BACKGROUND: Clinical practice guidelines (CPG) endorse multiple strategies to
      prevent or manage preterm birth (PTB). OBJECTIVES: To summarise CPG
      recommendations for PTB and identify areas of international consensus. SEARCH
      STRATEGY: In May 2017 we searched for all CPG relevant to PTB without language
      restrictions. SELECTION CRITERIA: CPG were eligible if the following criteria
      were met: (1) the guideline was published or current from June 2013; (2) the
      guideline recommended practices for the prevention or management of PTB relevant
      to our prespecified clinical questions for screening, medications or surgery and
      other interventions; (3) publications on methods of guideline development for
      eligible CPG were included to enable quality assessment. DATA COLLECTION AND
      ANALYSIS: Two authors classified CPG recommendations relevant to prespecified
      clinical questions. When more than 70% of CPGs reporting on a topic recommended
      or rejected an intervention, we regarded this as consensus. We summarised
      recommendations in tables. MAIN RESULTS: We identified 49 guidelines from 16
      guideline developers. We found consensus for several clinical practices: cervical
      length screening for high-risk women; short-term tocolysis; steroids for fetal
      lung maturation; and magnesium sulphate for fetal neuroprotection. We found
      discrepant recommendations for progesterone and fibronectin. No guideline
      identified an effective strategy for women with multiple pregnancy. CONCLUSIONS:
      We identified interventions for which there is an international consensus on
      benefit for PTB. Systematic reviews of CPG using standardised methodology will
      help avoid duplication and target scarce resources for guideline developers
      globally. TWEETABLE ABSTRACT: International clinical guidelines agree on the
      benefits and harmful effects of several important interventions to prevent
      preterm birth.

PMID- 29460324
TI  - Peri-prostatic adipose tissue: the metabolic microenvironment of prostate cancer.
AB  - Emerging data have linked certain features of clinical prostate cancer (PCa) to
      obesity and, more specifically, increased adiposity. Whereas the large number of
      clinical studies and meta-analyses that have explored the associations between
      PCa and obesity have shown considerable variability, particularly in relation to
      prostate cancer risk, there is an accumulating weight of evidence consistently
      linking obesity to greater aggressiveness of disease. In probing this association
      mechanistically, it has been posited that peri-prostatic adipose tissue (PPAT), a
      significant component of the prostate microenvironment, may be a critical source
      of fatty acids and other mitogens and thereby influences PCa pathogenesis and
      progression. Notably, several recent studies have identified secreted factors
      from both PPAT and PCa that potentially mediate the two-way communication between
      these intimately linked tissues. In the present review, we summarize the
      available literature regarding the relationship between PPAT and PCa, including
      the potential biological mediators of that relationship, and explore emerging
      areas of interest for future research endeavours.

PMID- 29460325
TI  - Estrogenic and anti-estrogenic activity of butylparaben, butylated
      hydroxyanisole, butylated hydroxytoluene and propyl gallate and their binary
      mixtures on two estrogen responsive cell lines (T47D-Kbluc, MCF-7).
AB  - The estrogenic and anti-estrogenic effects of butylparaben (BuPB), butylated
      hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) were
      evaluated for individual compounds as well as for binary mixtures, using an
      estrogen-dependent reporter gene assay in T47D-Kbluc breast cancer cells and an
      estrogen-dependent proliferation assay in MCF-7 breast cancer cells. In terms of
      estrogenicity the potency of the selected compounds increased from BHA < PG <
      BuPB in the luciferase assay (with BHT showing no significant estrogenic
      activity), while in the proliferation assay the following order was observed: BHT
      < BHA < BuPB (with PG showing no significant estrogenic activity). Non-monotonic
      dose-response curves were obtained for BuPB (in both assays) and PG (in the
      luciferase assay), respectively. In the presence of estradiol, a significant anti
      estrogenic activity was observed in both cell lines for PG, BuPB and BHA, while
      BHT showed weak anti-estrogenic activity only in T47D-Kbluc cells. The evaluation
      of binary mixtures confirmed the endocrine disruptive potential of the compounds,
      their individual potency being correlated with that of the mixtures. All mixtures
      were able to reduce the estradiol-induced luminescence or cell proliferation, an
      effect that was accurately predicted by the dose addition mathematical model,
      suggesting the same (or at least partially overlapping) modes of action for the
      tested compounds. The results of the present study emphasize the importance of a
      cumulative risk assessment of endocrine disruptors.

PMID- 29460326
TI  - Time for change: Renaming Diabetes Insipidus to improve patient safety.

PMID- 29460327
TI  - Contribution of dental tissues to sex determination in modern human populations.
AB  - OBJECTIVES: Accurate sex estimation is an essential step for the reconstruction
      of the biological profile of human remains. Earlier studies have shown that
      elements of the human permanent dentition are sexually dimorphic. The aims of
      this study are to determine the degree of sexual dimorphism in the dental tissue
      volumes and surface areas of mandibular canines and to explore its potential for
      reliable sex determination. METHOD: The teeth included in this study (n = 69)
      were selected from anthropological collections from Spain, South Africa and
      Sudan. In all cases, the sex of the individuals was known. The teeth were scanned
      and three-dimensional (3D) measurements (volumes and surfaces areas) were
      obtained. Finally, a dsicriminant function analysis was applied. RESULTS: Our
      results showed that sexual dimorphism in canine size is due to males having
      greater amounts of dentine, whereas enamel volume does not contribute
      significantly to overall tooth size dimorphism. Classification accuracy of the
      multivariable equations tested on slightly worn teeth ranged from 78 to 90.2% for
      the crossvalidation, and from 71.43 to 84.62% for the hold-out sample validation.
      When all functions were applied together, the sex was correctly assigned 92.30%
      of the time. CONCLUSIONS: Our results suggest that the 3D variables from
      mandibular canine dental tissues are useful for sex determination as they present
      a high degree of dimorphism. The results obtained show the importance of 3D
      dental tissue measurements as a methodology in sex determination, which
      application should be considered as a supplemental method to others.

PMID- 29460328
TI  - Predictive Models Control of the Artificial Pancreas: Compartmental or Neural
      Networks Models?

PMID- 29460329
TI  - Population-based testing of non-mucinous epithelial ovarian cancer in Scotland.

PMID- 29460330
TI  - Prospective evaluation of an indwelling esophageal balloon dilatation feeding
      tube for treatment of benign esophageal strictures in dogs and cats.
AB  - BACKGROUND: Despite multiple dilatation procedures, benign esophageal strictures
      (BES) remain a recurring cause of morbidity and mortality in dogs and cats.
      OBJECTIVE: Investigate the use of an indwelling Balloon Dilatation esophagostomy
      tube (B-Tube) for treatment of BES in dogs and cats. ANIMALS: Nine dogs and 3
      cats. METHODS: Animals with BES were recruited for our prospective study.
      Endoscopic and fluoroscopic evaluation of the esophagus and balloon dilatation
      were performed under general anesthesia, followed by placement of an indwelling B
      Tube. The animals' owners performed twice daily at-home inflations for
      approximately 6 weeks. Repeat endoscopy was performed before B-Tube removal.
      Animals were reevaluated for changes in modified dysphagia score (MDS) after B
      Tube removal. RESULTS: The B-Tube management was relatively well tolerated and
      effective in maintaining dilatation of a BES while in place. These animals
      underwent a median of 2 anesthetic episodes and were monitored for a median of
      472 days (range, 358-1736 days). The mean MDS before treatment was 3.1 +/-
      0.5/4.0 and final follow-up MDS were significantly (P < .0001) improved at 0.36
      +/- 0.65/4.0. Eleven of 12 animals (91.7%) had improved MDS at the end of the
      follow-up period, with 8/12 (66.7%) having an MDS of 0/4, 2/12 (16.7%) an MDS of
      1/4, and 1/12 (8.3%) an MDS of 2/4. One dog died. CONCLUSIONS AND CLINICAL
      IMPORTANCE: The B-Tube offers an effective, and more economical method, and often
      decreased anesthetic time to repeated balloon dilatation procedures for the
      treatment of BES in dogs and cats.

PMID- 29460331
TI  - Clinical and Neuroimaging Findings in Thalamic Territory Infarctions: A Review.
AB  - The thalamus is a part of the diencephalon, containing numerous connections
      between the forebrain and subcortical structures. It serves an important function
      as a relay center between the cerebral cortex and the subcortical regions,
      particularly with sensory information. The thalamus also plays a major role in
      regulating arousal and the levels of awareness. Distinct vascular distribution of
      the thalamus give rises to different syndromic presentation of thalamic nuclei
      infarcts. The clinical records and available imaging studies of patients with
      confirmed thalamic territory infarcts on magnetic resonance imaging (MRI) at the
      University Hospital of Rochester were reviewed and analyzed. This analysis was
      then used to provide an effective summary of thalamic vascular anatomy, the
      clinical symptoms, and syndromes associated with strokes in the affected
      territories. Specifically, we review the syndromes associated with classic
      vascular territories, including the anterior, paramedian, inferolateral, and
      posterior thalamic nuclei, that are supplied by the polar (tuberothalamic),
      paramedian, inferolateral (thalamogeniculate), and posterior choroidal arteries,
      respectively. In addition, we will also review the variant thalamic territories
      and associated infarction syndromes of the anteromedian, central, and
      posterolateral territories. This review article is aimed to better the clinical
      and radiologic understanding as well as the diagnosis of classic and variant
      thalamic territory infarcts. This article will also briefly touch on the recovery
      of function after thalamic infarcts.

PMID- 29460332
TI  - Vitamin D levels in acne vulgaris patients treated with oral isotretinoin.
AB  - BACKGROUND/OBJECTIVES: Acne vulgaris is a common inflammatory skin disease.
      Vitamin D deficiency plays a role in many inflammatory skin diseases. It may play
      a role in pathogenesis of acne vulgaris. This study aimed to assess serum levels
      of 25 hydroxy vitamin D in patients with acne vulgaris before and after treatment
      with isotretinoin and its relation with acne vulgaris severity. METHODS: Ninety
      patients with acne vulgaris and 60 age-sex matched healthy subject as controls
      have been recruited in this study. Patients were treated with 0.75 mg/kg/d
      isotretinoin for 3 months. Serum level of 25 hydroxy vitamin D has been measured
      at baseline and after treatment. RESULTS: Serum levels of 25 hydroxy vitamin D
      were significantly higher in patients with acne vulgaris than healthy controls (P
      = .001). There was a significant inverse relation between level of 25 hydroxy
      vitamin D and severity of acne vulgaris before treatment (P = .001). Serum levels
      of 25 hydroxy vitamin D were significantly increased after isotretinoin treatment
      in patients with acne vulgaris (P = .001). CONCLUSION: This study concluded that
      vitamin D may play a potential role in pathogenesis of acne vulgaris or acne
      vulgaris may have a negative effect on vitamin D synthesis. Further studies are
      needed to confirm these potential relations.

PMID- 29460333
TI  - Comparison of diagnostic accuracy of laparoscopic 3 mm and 5 mm cup biopsies to
      wedge biopsies of canine livers.
AB  - BACKGROUND: Diagnostic accuracy of the 3 mm laparoscopic cup biopsy forceps for
      collection of tissue samples from canine livers is unproven.
      HYPOTHESES/OBJECTIVES: Compare sample surface area and portal triad count between
      3 mm and 5 mm laparoscopic cup biopsies and compare the histologic diagnosis
      obtained by each instrument to a standard necropsy wedge. The hypothesis was that
      more portal triads and greater sample surface area would be found with the 5 mm
      samples and the laparoscopic instruments would not have significantly different
      levels of agreement with necropsy wedge diagnosis. ANIMALS: Twenty-one client
      owned dogs undergoing necropsy. METHODS: Prospective ex vivo study. Three samples
      (3 mm, 5 mm, and wedge) were taken of 2 different hepatic divisions within 24
      hours of death. Morphologic diagnosis, World Small Animal Veterinary Association
      histologic features, surface area, and portal triad numbers were compared among
      the 3 samples. RESULTS: There were significantly more portal triads (mean 21.4
      versus 13.8; P < .0001) and a higher surface area (20.3 mm2 versus 11.5 mm2 ; P <
      .0001) in the 5 mm samples compared to 3 mm samples. Kappa coefficients and
      percent agreement for histologic diagnosis as compared to the wedge biopsy were
      not significantly different between the 2 instrument sizes (kappa = 0.383 and
      0.436, respectively; 67% and 69%, respectively). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Despite yielding smaller sample sizes, the 3 mm laparoscopic cup
      biopsy has a similar level of histologic diagnostic accuracy to the 5 mm
      instrument.

PMID- 29460334
TI  - Variation of renal function over time is associated with major bleeding in
      patients treated with direct oral anticoagulants for atrial fibrillation.
AB  - : Essential In patients on treatment with direct anticoagulants (DOACs) variation
      of renal function is common. The effect of variations of renal function over time
      on major bleeding is not well defined. Variation of renal function over time is
      an independent predictor of major bleeding. Identifying conditions associated
      with variation of renal function may increase safety of DOACs. SUMMARY:
      Background Chronic kidney disease is a risk factor for major bleeding in patients
      with atrial fibrillation (AF) treated with warfarin. Objective To assess the
      effect of variations in renal function over time on the risk of major bleeding
      during treatment with direct oral anticoagulants (DOACs) in patients with non
      valvular AF. Methods Consecutive AF patients were prospectively followed after
      they had received the first DOAC prescription. Estimated glomerular filtration
      rate (eGFR) was periodically assessed, and the incidence of major bleeding was
      recorded. A joint survival model was used to estimate the association between
      variation in eGFR and the risk of major bleeding. Results During a mean follow-up
      of 575 days, 44 major bleeds occurred in 449 patients (6.1% per patient-year).
      eGFR over time was inversely and independently associated with the risk of major
      bleeding; every 1 mL min-1 absolute decrease in eGFR was associated with a 2%
      increase in the risk of major bleeding (hazard ratio [HR] 1.02, 95% confidence
      interval [CI] 1.01-1.04). A similar effect of the variation in eGFR over time was
      observed on the risk of clinically relevant non-major bleeding (HR 1.02, 95% CI
      1.01-1.03). Deterioration of renal function leading to a change in eGFR staging
      was associated with an increase in the risk of major bleeding (HR 2.43, 95% CI
      1.33-4.45). Conclusions Variation in renal function over time is associated with
      the risk of major bleeding in AF patients treated with DOACs in real life.
      Identification of intervening clinical conditions associated with variation in
      renal function is essential to reduce the risk of major bleeding and to make DOAC
      treatment more safe.

PMID- 29460335
TI  - Liposomal Treatment of Cancer Cells Modulates Uptake Pathway of Polymeric
      Nanoparticles by Altering Membrane Stiffness.
AB  - Nanomedicines can be taken up by cells via nonspecific and dynamin-dependent
      (energy-dependent) clathrin and caveolae-mediated endocytosis. While significant
      effort has focused on targeting pathway-specific transporters, the role of
      nanobiophysics in the cell lipid bilayer nanoparticle uptake pathway remains
      largely unexplored. In this study, it is demonstrated that stiffness of lipid
      bilayer is a key determinant of uptake of liposomes by mammalian cells. Dynamin
      mediated endocytosis (DME) of liposomes is found to correlate with its phase
      behavior, with transition toward solid phase promoting DME, and transition toward
      fluidic phase resulting in dynamin-independent endocytosis. Since liposomes can
      transfer lipids to cell membrane, it is sought to engineer the biophysical
      properties of the membrane of breast epithelial tumor cells (MD-MBA-231) by
      treatment with phosphatidylcholine liposomes, and elucidate its effect on the
      uptake of polymeric nanoparticles. Analysis of the giant plasma membrane vesicles
      derived from treated cells using flicker spectroscopy reveals that liposome
      treatment alters membrane stiffness and DME of nanoparticles. Since liposomes
      have a history of use in drug delivery, localized priming of tumors with
      liposomes may present a hitherto unexploited means of targeting tumors based on
      biophysical interactions.

PMID- 29460336
TI  - Emollient product design: objective measurements of formulation structure,
      texture and performance, and subjective assessments of user acceptability.
AB  - BACKGROUND: The choice of prescribed emollients is usually based on cost and
      patient preference. Differences in formulations can affect user acceptability.
      AIM: To compare the physical performance, user acceptability and various product
      design features of two emollient gels that are prescribed in the UK and alleged
      to be therapeutically interchangeable because their formulations are described as
      having the same contents of oily ingredients. RESULTS: We found that here are in
      fact significant measurable differences between the structure and performance of
      the two formulations, which materially affect their user acceptability. These
      differences are attributed to the use of different types of gelling agents and
      other ingredients of differing grades/quality and concentrations, and probably
      due to the formulations being made by different manufacturing processes. We also
      identified other product design features that are important to user appeal,
      including the type of container in which the formulations are presented, the type
      of dispensing devices provided, and the nature and form of the supplied user
      instructions. CONCLUSION: Patients and prescribers should be aware that there can
      be important differences in performance and user appeal between emollients, even
      between products that, superficially, may appear to be very similar. These
      important performance aspects should be characterized for new emollient
      introductions to encourage better informed product selection.

PMID- 29460337
TI  - A pilot study to evaluate the effectiveness of an individualized and cognitive
      behavioural communication intervention for informal carers of people with
      dementia: The Talking Sense programme.
AB  - BACKGROUND: People with dementia and family carers often experience difficulties
      communicating together. These difficulties are considered to contribute
      significantly to the depression, anxiety and negative feelings such as guilt
      often reported by dementia family carers. AIMS: To develop and contribute to the
      theory and evidence base for single-component, psychosocial interventions that
      address these difficulties by evaluating the effectiveness of the Talking Sense
      programme which was designed to reflect existing best evidence. METHODS &
      PROCEDURES: Talking Sense was delivered as an individualized, one to one,
      cognitive behavioural approach for developing knowledge, skills, thinking and
      behaviour of dementia family carers in managing communication difficulties. In
      this study, a randomized controlled trial compared 27 carers who completed three
      one-to-one individualized sessions using Talking Sense with 25 carers who
      received a single, knowledge-only, control discussion. OUTCOMES & RESULTS: There
      were no significant differences for the primary outcome measure of carer anxiety
      and depression as well as carer quality of life and general self-efficacy.
      Statistically significant results suggested carers receiving the Talking Sense
      intervention had fewer communication difficulties happening (p = 0.046) and felt
      more valued by their relatives (p = 0.046). A score close to significance (p =
      0.052) suggested they perceived their relatives to be more communicatively
      competent. CONCLUSIONS & IMPLICATIONS: The intervention and research design were
      shown to be effective with low attrition and high adherence to treatment. A non
      significant finding for the primary outcome measure does not support the
      potential for this intervention to effect carer anxiety and depression. The
      potential for perceived change in the person with dementia, with statistically
      fewer communication difficulties happening and the carer feeling more valued by
      their relative, was the most significant finding from this programme of research.
      Recommendations for further research are made.

PMID- 29460339
TI  - Protective effect of ghrelin on testicular damages caused by chronic hypoxia in
      rats: A histopathological study.
AB  - Hypoxia can lead to changes in the blood flow, nutrition and oxygenation of male
      germ cells and results in fertility reduction through the increase in oxidative
      stress. This study aims to evaluate the effect of ghrelin on testicular damage
      induced by hypoxia in rats. In this experimental study, 24 male rats were
      randomly divided into four groups: control, hypoxia, hypoxia + ghrelin and
      ghrelin. Animals in the control and ghrelin groups were kept in room air with 21%
      oxygen. The animals in the groups of hypoxia and hypoxia + ghrelin were subjected
      to 11% oxygen for 14 consecutive days in the hypoxia chamber. At the end of the
      study, the testes were removed and histological changes, as well as the apoptotic
      index, were investigated. Morphometrical analysis showed that hypoxia caused a
      significant decrease in the seminiferous tubules diameter, the germinal
      epithelium thickness and main Johnson's score compared to the control group (p <
      .05). In addition, statistical comparisons revealed a significant increase in the
      apoptotic index in the hypoxia group (p < .05). Administration of ghrelin +
      hypoxia improved the parameters mentioned above (p < .05). The results of this
      study indicated that ghrelin decreases the testicular damages caused by hypoxia
      in the rats by antioxidative activity.

PMID- 29460338
TI  - MDSCs drive the process of endometriosis by enhancing angiogenesis and are a new
      potential therapeutic target.
AB  - Endometriosis affects women of reproductive age via unclear immunological
      mechanism(s). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group
      of myeloid cells with potent immunosuppressive and angiogenic properties. Here,
      we found MDSCs significantly increased in the peripheral blood of patients with
      endometriosis and in the peritoneal cavity of a mouse model of surgically induced
      endometriosis. Majority of MDSCs were granulocytic, produced ROS, and arginase,
      and suppressed T-cell proliferation. Depletion of MDSCs by antiGr-1 antibody
      dramatically suppressed development of endometrial lesions in mice. The
      chemokines CXCL1, 2, and 5 were expressed at sites of lesion while MDSCs
      expressed CXCR-2. These CXC-chemokines promoted MDSC migration toward
      endometriotic implants both in vitro and in vivo. Also, CXCR2-deficient mice show
      significantly decreased MDSC induction, endometrial lesions, and angiogenesis.
      Importantly, adoptive transfer of MDSCs into CXCR2-KO mice restored endometriotic
      growth and angiogenesis. Together, this study demonstrates that MDSCs play a role
      in the pathogenesis of endometriosis and identifies a novel CXC-chemokine and
      receptor for the recruitment of MDSCs, thereby providing a potential target for
      endometriosis treatment.

PMID- 29460340
TI  - Evaluation of In Vitro alpha-Amylase and alpha-Glucosidase Inhibitory Potentials
      of 14 Medicinal Plants Constituted in Thai Folk Antidiabetic Formularies.
AB  - The sporadic increase in the occurrence and prevalence of diabetes mellitus have
      compelled and vigorous search for alternative anti-diabetic therapeutic approach
      from medicinal plants and its bioactive. One of the major approach employed is
      the reduction of gastrointestinal glucose levels through the inhibition of
      carbohydrate digesting enzymes notably alpha-amylase and alpha-glucosidase. In
      this study, the ethanol extracts of 14 selected plants from Mor Porn's recipe
      were screened for their alpha-amylase and alpha-glucosidase inhibitory activity.
      The ethanolic extract from the stem of Vitex glabrata displayed the highest
      percentage inhibitory activity of 84.98 +/- 0.59 and 84.71 +/- 1.51 against alpha
      glucosidase and alpha-amylase enzymes, respectively. Chemical investigation of
      the active extract of V. glabrata indicated that pentacyclic triterpenes were the
      major compounds responsible for the activity. The result obtained from this study
      suggests the potential use of V. glabrata as an alternative natural source for
      the treatment of diabetes mellitus.

PMID- 29460341
TI  - Continuing rise of Type 2 diabetes incidence in children and young people in the
      UK.
AB  - AIMS: To estimate the incidence of Type 2 diabetes in children aged <17 years,
      compare this with similar data 10 years ago, and characterize clinical features
      at diagnosis in the UK and Republic of Ireland. METHODS: Using the British
      Paediatric Surveillance Unit reporting framework, cases of Type 2 diabetes
      diagnosed in children aged <17 years between 1 April 2015 and 30 April 2016 were
      reported each month. RESULTS: A total of 106 cases were reported, giving a UK
      incidence of 0.72/100 000 (95% CI 0.58-0.88). Children from ethnic minorities had
      significantly higher incidence compared with white children (0.44/100 000) with
      rates of 2.92/100 000 and 1.67/100 000, in Asian and BACBB
      (black/African/Caribbean/black British) children respectively. Sixty-seven
      percent were girls and 81% had a family history of Type 2 diabetes. The mean BMI
      sd score at diagnosis was 2.89 (2.88, girls; 2.92, boys); 81% were obese.
      Children of Asian ethnicity had a significantly lower BMI sd score compared with
      white children (P<0.001). There was a trend in increased incidence from 2005 to
      2015, with a rate ratio of 1.35 (95% CI 0.99-1.84), although this was not
      statistically significant (P=0.062). There was statistical evidence of increased
      incidence among girls (P=0.03) and children of South-Asian ethnicity (P=0.01)
      when comparing the 2005 and 2015 surveys. CONCLUSIONS: Type 2 diabetes remains
      far less common than Type 1 diabetes in childhood in the UK, but the number of
      cases continues to rise, with significantly increased incidence among girls and
      South-Asian children over a decade. Female gender, family history, non-white
      ethnicity and obesity were found to be strongly associated with the condition.

PMID- 29460343
TI  - NiH-Catalyzed Reductive Relay Hydroalkylation: A Strategy for the Remote C(sp3 )
      H Alkylation of Alkenes.
AB  - The terminal-selective, remote C(sp3 )-H alkylation of alkenes was achieved by a
      relay process combining NiH-catalyzed hydrometalation, chain walking, and
      alkylation. This method enables the construction of unfunctionalized C(sp3 )
      C(sp3 ) bonds under mild conditions from two simple feedstock chemicals, namely
      olefins and alkyl halides. The practical value of this transformation is further
      demonstrated by the large-scale and regioconvergent alkylation of isomeric
      mixtures of olefins at low catalyst loadings.

PMID- 29460344
TI  - The Two Cultures: Where are we now?
AB  - In 1959 the physicist and novelist C. P. Snow described a schism in Western
      society. He said that the Sciences and the Arts were, in effect, 'two cultures'.
      How does that appraisal look to us now? This article looks at a development Snow
      cannot have anticipated - the current academic orthodoxy of 'Critical Theory',
      and an associated mistrust of scientific knowledge ....

PMID- 29460346
TI  - Comparison of the ecarin chromogenic assay and diluted thrombin time for
      quantification of dabigatran concentrations: comment.

PMID- 29460345
TI  - Comparative virulence of Candida auris with Candida haemulonii, Candida glabrata
      and Candida albicans in a murine model.
AB  - The incidence of invasive fungal infections (IFIs) caused by uncommon Candida
      species with diverse virulence and susceptibility profiles has increased in
      recent years. Due to scarce clinical and experimental data on the pathogenicity
      of Candida auris, the aim of this study was to evaluate and compare the virulence
      of two rare clinically relevant species, C. auris and Candida haemulonii with
      Candida glabrata and Candida albicans in an immunocompetent murine model of
      disseminated infection. Immunocompetent ICR female mice were infected with three
      inoculum sizes (1 * 105 , 1 * 106 and 1 * 107 CFU/mouse) of two C. auris strains
      and one isolate of C. haemulonii, C. glabrata and C. albicans. Tissue burden on
      days 5 and 10 postchallenge and mortality rate were used as virulence markers. A
      high virulence was found for C. albicans, followed by C. auris, C. glabrata and
      C. haemulonii, respectively. Candida albicans showed high virulence with a medium
      survival time of 9.5 days for mice infected with 1 * 107 CFU/mouse. For inocula
      at 1 * 106 and 1 * 107 CFU/mouse, there were significant differences in fungal
      burden at day 10 between C. albicans, C. auris and C. glabrata isolates compared
      with C. haemulonii (P < .0001). Overall, no significant differences between C.
      albicans with C. auris and C. glabrata were observed in mice infected with three
      different inocula (P > .05). In general, the highest fungal load of all isolates
      was detected in kidney followed by spleen, liver and lung tested with three
      different inocula on the two different experimental days. Histopathological
      examination revealed the abundant presence of yeast cells with pseudohyphae for
      C. albicans and only yeast cells for C. auris, C. glabrata and C. haemulonii, in
      all the kidney tissue samples. In conclusion, C. albicans is a highly virulent
      opportunistic fungus, as the clinical and experimental data demonstrate, and also
      our results demonstrate a low virulence of C. haemulonii in immunocompetent
      animals. Altogether, this study highlights the pathogenic potential of C. auris.

PMID- 29460347
TI  - Human skin in vivo has a higher skin barrier function than porcine skin ex vivo
      comprehensive Raman microscopic study of the stratum corneum.
AB  - Porcine skin is widely used as a human skin model in dermatology. For both,
      porcine stratum corneum (SC) ex vivo and human SC in vivo, the hydrogen bonding
      states of water, the secondary and tertiary structures of keratin, the natural
      moisturizing factor (NMF) concentrations and the intercellular lipids' (ICL)
      lateral organization are investigated depth-dependently using confocal Raman
      microscopy. The SC depth profiles show that porcine SC ex vivo is characterized
      by lower hydrogen bonding states of water (10%-30% SC depth), lower NMF
      concentration in the whole SC, more beta-sheet form of keratin (10%-90% SC
      depth), more folded tertiary keratin structures (30%-70% SC depth) and higher
      hexagonal lateral packing order of ICL (10%-50% SC depth) compared to human SC in
      vivo. The results clearly show a higher value of skin barrier function of human
      SC in vivo than of porcine SC ex vivo. Thus, the human SC in vivo is less
      permeable for lipophilic and hydrophilic substances than porcine SC ex vivo.
      Considering the porcine SC as an ex vivo model of human SC in vivo, these
      findings should be taken into consideration.

PMID- 29460349
TI  - Adolescent Brain Development: Implications for Understanding Risk and Resilience
      Processes Through Neuroimaging Research.
AB  - This special section focuses on research that utilizes neuroimaging methods to
      examine the impact of social relationships and socioemotional development on
      adolescent brain function. Studies include novel neuroimaging methods that
      further our understanding of adolescent brain development. This special section
      has a particular focus on how study findings add to our understanding of risk and
      resilience. In this introduction to the special section, we discuss the role of
      neuroimaging in developmental science and provide a brief review of neuroimaging
      methods. We present key themes that are covered in the special section articles
      including: (1) emerging methods in developmental neuroscience, (2) emotion
      cognition interaction, and (3) the role of social relationships in brain
      function. We conclude our introduction with future directions for integrating
      developmental neuroscience into the study of adolescence, and highlight key
      points from the special section's commentaries which include information on the
      landmark Adolescent Brain Cognitive Development (ABCD) study.

PMID- 29460348
TI  - Positive and Negative Affect and Adolescent Adjustment: Moderation Effects of
      Prefrontal Functioning.
AB  - We examined whether cognitive control moderates the effects of emotion on
      adolescent internalizing and externalizing symptomatology in a longitudinal study
      of 138 adolescents. Self-reported positive affect (PA) and negative affect and
      behavioral and neural indicators of cognitive control, indexed by performance and
      prefrontal hemodynamic response during a cognitive interference task, were
      collected at Time 1. Self-reported internalizing and externalizing symptomatology
      were collected at Time 1 and Time 2 (1 year later). Results indicated that higher
      PA predicted decreases in externalizing symptomatology, but only for adolescents
      with poor neural cognitive control. No moderation effects were found for
      behavioral cognitive control. Findings imply the beneficial effects of PA on the
      development of externalizing problems among adolescents with poor prefrontal
      functioning.

PMID- 29460351
TI  - Dyadic Neural Similarity During Stress in Mother-Child Dyads.
AB  - Shared psychological processes between individuals occur most between a mother
      and her child because the mother-child bond is one of the closest forms of human
      attachment, in which a mother and her child are essentially wired to connect. We
      recruited mother-child pairs (Ndyad  = 19; adolescent: Mage  = 13.74, 11 males;
      mothers: Mage  = 44.26), who each completed an fMRI scan. We examined dyadic
      neural representational similarity as adolescents completed a stress task and
      mothers observed their child's performance during the same task. On average,
      mothers and their children did not show similar neural patterns during stress.
      However, neural similarity varied depending on family connectedness, such that
      only dyads reporting high family connectedness showed similar neural profiles.
      Importantly, increased neural similarity was associated with reduced stress in
      youth, suggesting that shared neural profiles in mother-child dyads enhance
      adolescents' psychological well-being.

PMID- 29460350
TI  - Pathways to Youth Behavior: The Role of Genetic, Neural, and Behavioral Markers.
AB  - Neural and temperamental mechanisms through which a genetic risk marker in the
      gamma-amino butyric acid alpha2 receptor subunit (GABRA2) impacts adolescent
      functioning were investigated. Participants (N = 80; 29 female) completed an
      emotional word task during functional magnetic resonance imaging. Behavioral
      control, negative emotionality, and resiliency temperament constructs were
      assessed. Externalizing and internalizing problems were the outcomes. Those with
      the GABRA2 minor allele had reduced activation to positive words in the angular
      gyrus, middle temporal gyrus, and cerebellum, and to negative words in frontal,
      parietal, and occipital cortices. Reduced activation in the angular gyrus
      predicted greater negative emotionality and, in turn, elevated externalizing
      problems. Reduced activation in the inferior parietal cortex predicted greater
      resiliency and, in turn, low externalizing problems.

PMID- 29460352
TI  - The Adolescent Brain Cognitive Development Study.

PMID- 29460353
TI  - A Ripe Time for Adolescent Research.

PMID- 29460354
TI  - Longitudinal Associations Between Family Aggression, Externalizing Behavior, and
      the Structure and Function of the Amygdala.
AB  - Using longitudinal data from 21 adolescents, we assessed family aggression (via
      mother, father, and youth report) in early adolescence, externalizing behavior in
      mid-adolescence, and magnetic resonance imaging (MRI) data in late adolescence.
      Amygdalae were manually traced, and used as seed regions for resting state
      analyses. Both family aggression and subsequent externalizing behavior predicted
      larger right amygdala volumes and stronger amygdala-frontolimbic/salience network
      connectivity and weaker amygdala-posterior cingulate connectivity. Externalizing
      behavior in mid-adolescence mediated associations between family aggression in
      early adolescence and resting state connectivity between the amygdala and the
      subgenual anterior cingulate cortex, medial prefrontal cortex, orbitofrontal
      cortex, and posterior cingulate cortex in late adolescence. Family adversity and
      adolescent behavior problems may share common neural correlates.

PMID- 29460356
TI  - Broadening the Impact of Developmental Neuroscience on the Study of Adolescence.
AB  - Having been a significance source of the renewed interested in the adolescent
      period, developmental neuroscience now needs to build upon its achievements to
      date and expand in several areas in order to broaden its impact upon the field.
      Addressing both typical and atypical development, examining the interaction
      between brain development and the social environment, studying change over time,
      and including attention to population diversity can help to produce a truly
      integrative science of adolescent development. The papers in the special section
      provide nice examples of how developmental neuroscience can make such expansions
      and continue to contribute to the field in the years to come.

PMID- 29460355
TI  - Do Hostile School Environments Promote Social Deviance by Shaping Neural
      Responses to Social Exclusion?
AB  - The present study examined adolescents' neural responses to social exclusion as a
      mediator of past exposure to a hostile school environment (HSE) and later social
      deviance, and whether family connectedness buffered these associations.
      Participants (166 Mexican-origin adolescents, 54.4% female) reported on their HSE
      exposure and family connectedness across Grades 9-11. Six months later, neural
      responses to social exclusion were measured. Finally, social deviance was self
      reported in Grades 9 and 12. The HSE-social deviance link was mediated by greater
      reactivity to social deviance in subgenual anterior cingulate cortex, a region
      from the social pain network also implicated in social susceptibility. However,
      youths with stronger family bonds were protected from this neurobiologically
      mediated path. These findings suggest a complex interplay of risk and protective
      factors that impact adolescent behavior through the brain.

PMID- 29460357
TI  - Neural Correlates of Risky Sex and Response Inhibition in High-Risk Adolescents.
AB  - Adolescence is a neurodevelopmental period of heightened sexual risk taking.
      Neuroimaging can help elucidate crucial neurocognitive mechanisms underlying
      adolescent sexual risk behavior, yet few empirical studies have investigated this
      neural link. To address this gap in the literature, we examined the association
      between neurocognitive function during response inhibition-a known correlate of
      risk behaviors-and frequency of intercourse without a condom among adolescents.
      We examined the correlation between condom use and fMRI-based Stroop response in
      a large ethnically diverse sample of high-risk adolescents (n = 171). Partially
      replicating previous literature, sexual risk was positively correlated with blood
      oxygen-level-dependent (BOLD) activation in the middle frontal gyrus during
      response inhibition, highlighting the relevance of this region during risky
      sexual decision making within this age group.

PMID- 29460358
TI  - Role of Social Environmental Protective Factors on Anxiety and Depressive
      Symptoms Among Midwestern Homeless Youth.
AB  - We employ a social stress framework, which examines the influence of multiple
      stressors (e.g., physical abuse, foster care placement) on an individual's
      ability to function (e.g., mental well-being), to longitudinally examine the
      effects of stressful life events on mental health and the role of the social
      environment in this process among 150 homeless youth. Results revealed that
      numerous stressors, such as physical abuse and running away from home more
      frequently, were associated with greater depressive symptoms and elevated
      anxiety. Having mentors and family and friends from home that youth can rely on
      resulted in more positive social support, which subsequently lowered the risk for
      depressive symptoms and anxiety at wave 2.

PMID- 29460359
TI  - Connecting Theory and Methods in Adolescent Brain Research.
AB  - Networks are often implicated in theories of adolescent brain development, but
      they are not regularly examined in empirical studies. The aim of this article is
      to address this disconnect between theory and quantitative methodology, using the
      dual systems model of adolescent decision making as a prototype. After reviewing
      the key task-related connectivity methods that have been applied in the
      adolescent neuroimaging literature (seed-based correlations, psychophysiological
      interactions, and dynamic causal modeling), a novel connectivity method is
      introduced (extended unified structural equation modeling). The potential of this
      method for understanding adolescent brain development is showcased with a
      simulation study: It creates person-specific networks that have direct and time
      lagged connections that can be modulated by behavior.

PMID- 29460360
TI  - A Three-Year Emotional Intelligence Intervention to Reduce Adolescent Aggression:
      The Mediating Role of Unpleasant Affectivity.
AB  - Adolescents' aggressive behavior is a growing social problem with important
      implications for psychosocial adjustment. The teaching of emotional skills has an
      important impact on reducing aggression in schools. However, little scientific
      evidence has shown the explanatory mechanism through which this training reduces
      aggression during adolescence. This article aims to provide evidence for the
      effectiveness of a 3-year longitudinal intervention among adolescents in nine
      Spanish schools. A total of 476 adolescents participated. Results showed a
      reduction in physical and verbal aggression in Time 2 through the reduction in
      negative affect, anger, and hostile feelings, compared with an active control
      group. The training seems to be crucial for dealing with the emotional and
      cognitive components of aggression and, thus, their behavioral manifestations.

PMID- 29460361
TI  - Attentional Bias for Academic Stressors and Classroom Climate Predict
      Adolescents' Grades and Socioemotional Functioning.
AB  - Using a dot-probe detection task, this longitudinal study investigated whether
      adolescents show an attentional bias for academic stressors at the beginning of
      the school year (T1), and if such allocation of attention interacts with
      classroom climate (CC) to predict grades and socioemotional functioning at the
      end of the term (T2). Among 133 eighth-graders, the majority showed a perceptual
      bias toward academic threats. Regression analyses indicated that a greater bias
      at T1 predicted lower grades and more socioemotional problems at T2, and that CC
      moderated these relationships. Students perceiving low CC and displaying greater
      attentional bias reported lower grades and more socioemotional problems. Teachers
      may promote a positive CC to prevent the negative effects of a biased attention
      on youths' school adjustment.

PMID- 29460363
TI  - Neural Substrates of Counterfactual Emotions After Risky Decisions in Late
      Adolescents and Young Adults.
AB  - Adolescents' neural substrates of emotional reactions to the consequences of
      risky decisions are poorly understood. In this functional magnetic resonance
      imaging study, 30 late adolescents and 30 young adults made risky and neutral
      decisions in social scenarios and received valenced outcomes. Negative outcomes
      in risky decisions eliciting regret, as compared with negative outcomes in
      neutral decisions eliciting disappointment, activated executive control
      (orbitofrontal cortex) and self-relevance regions (middle temporal gyrus [MTG],
      posterior cingulate cortex, and precuneus) for both age groups. Young adults
      showed more activation than adolescents in regret and disappointment as compared
      with relief and elation conditions in the avoidance (insula), action monitoring
      (inferior frontal gyrus, pre-SMA, and caudate), and social-cognition regions
      (superior temporal sulcus and MTG). These late socio-emotional developments may
      pave the way for more adaptive decision-making behavior in social contexts.

PMID- 29460364
TI  - Longitudinal Transmission of Conflict Management Styles Across Inter-Parental and
      Adolescent Relationships.
AB  - This study longitudinally investigated transmission of conflict management styles
      across inter-parental, adolescent-parent, adolescent-friend, and adolescent
      partner relationships. During four waves, 799 middle-to-late adolescents (Mage-t1
      = 15.80; 54% boys) and their parents completed the Conflict Resolution Style
      Inventory. Cross-lagged path analyses indicated transmission of adolescent
      conflict management styles in relationships with parents to relationships with
      friends and romantic partners: Positive problem solving and conflict engagement
      utilized by adolescents in conflicts with parents were significantly, positively
      related to, respectively, adolescent positive problem solving and conflict
      engagement in relationships with friends 1 year later and relationships with
      partners 2 years later. Thus, the study showed that the way adolescents manage
      conflicts with parents predicts how they handle conflicts later in relationships
      outside the family.

PMID- 29460362
TI  - Prefrontal Cortical Response to Negative Social Words Links Social Risk to
      Depressive Symptoms in Adolescence.
AB  - Research suggests that altered emotion processing may be one important pathway
      linking social risk factors and depressive symptoms. We examined the extent to
      which neural response to negatively valenced social information might help to
      account for the relationship between social risk and depressive symptoms in
      youth. Forty-nine youth were scanned while identifying the emotional valence of
      words that connoted social status. They also completed questionnaires assessing
      self-reported social risk factors and depressive symptoms. Mediation analysis
      revealed that reduced dorsolateral prefrontal cortex activity in response to
      negative social status words explained the positive association between social
      risk and depressive symptoms. These findings suggest that social risk factors
      present during adolescence may contribute to depressive symptoms by influencing
      the neural substrates of emotion processing.

PMID- 29460365
TI  - A Capsule-Type Microrobot with Pick-and-Drop Motion for Targeted Drug and Cell
      Delivery.
AB  - A capsule-type microrobot exhibits "pick-and-drop" (P&D) motion to hold a
      particle within a confined volume and transports it via a corkscrewing motion.
      The P&D motion is possible because the capsule-type microrobot has two parts: a
      plunger and a cap. The fabricated microrobots are wirelessly controlled by a
      magnetic manipulator. Drugs or cells can be encapsulated in the container of the
      capsule-type microrobot by the P&D motion or attached to the surface of the cap,
      which can be used as a supporting structure. Therefore, the capsule-type
      microrobot can deliver suspended or adherent cells. The drug or cells are
      minimally exposed or not completely exposed to the surrounding fluid and do not
      experience shear force when encapsulated in the container. As a proof-of-concept,
      secure transportation of microparticles in the confined volume of the capsule via
      P&D motion is demonstrated. In addition, the cap is used as a scaffold for
      neuronal cell culture on a rat brain slice to demonstrate its biocompatibility
      and feasibility for targeted cell delivery. The proposed capsule-type microrobot
      is suitable for diverse applications, as it protects the encapsulated materials.

PMID- 29460366
TI  - Ejection fraction as a statistical index of left ventricular systolic function:
      the first full allometric scrutiny of its appropriateness and accuracy.
AB  - Left ventricular ejection fraction (EF) is a ratio that is deemed to accurately
      normalize stroke volume (SV) to end-diastolic volume (EDV). Ratios are now well
      recognized for not normalizing the numerator, in this case SV, consistently for
      the denominator, EDV. We aimed to provide the first allometric-based scrutiny of
      the conventional assumptions that underpin the EF ratio. We allometrically
      modelled untransformed SV and EDV measurements from 112 preclinical heart failure
      patients in the Multi-Ethnic Study of Atherosclerosis (MESA), and 864 chronic
      heart failure patients in the Treatment of Preserved Cardiac Function Heart
      Failure with an Aldosterone Antagonist (TOPCAT) study. An information-theoretic
      approach was adopted to assess the relative quality of twelve candidate models
      for normalizing SV to EDV. None of the conventional underlying assumptions for
      accurate ratio normalization, for example an allometric exponent ~1, were upheld
      for EF. A two-parameter power function with normal, heteroscedastic error was the
      best model for scaling SV to EDV in both samples. The allometric exponent (95%
      confidence interval) was 0.776 (0.682 to 0.869) in MESA, and 0.860 (0.857 to
      0.864) in TOPCAT. EF was inversely correlated with EDV in MESA (r = -0.67, 95%
      CI: -0.76 to -0.55) and TOPCAT (r = -0.41, 95% CI: -0.46 to -0.35). Consequently,
      for fundamental statistical reasons, EF was biased low for people with generally
      larger EDVs, and vice versa. For the first time, we have demonstrated that EF is
      an inaccurate statistic for scaling SV to EDV, leading to potential biased
      inferences for research and individual patients.

PMID- 29460367
TI  - Genetics in Macedonia-Following the international trends.
AB  - Genetics in Macedonia-Following the international trends.

PMID- 29460368
TI  - Immediate, short-, and long-term changes in tracheal stent diameter, length, and
      positioning after placement in dogs with tracheal collapse syndrome.
AB  - BACKGROUND: Intraluminal tracheal stenting is a minimally invasive procedure
      shown to have variable degrees of success in managing clinical signs associated
      with tracheal collapse syndrome (CTCS) in dogs. OBJECTIVES: Identify immediate
      post-stent changes in tracheal diameter, determine the extent of stent migration,
      and stent shortening after stent placement in the immediate-, short-, and long
      term periods, and evaluate inter-observer reliability of radiographic
      measurements. ANIMALS: Fifty client-owned dogs. METHODS: Retrospective study in
      which medical records were reviewed in dogs with CTCS treated with an
      intraluminal tracheal stent. Data collected included signalment, location, and
      type of collapse, stent diameter and length, and post-stent placement
      radiographic follow-up times. Radiographs were used to obtain pre-stent tracheal
      measurements and post-stent placement measurements. RESULTS: Immediate mean
      percentage change was 5.14%, 5.49%, and 21.64% for cervical, thoracic inlet, and
      intra-thoracic tracheal diameters, respectively. Ultimate mean follow-up time was
      446 days, with mean percentage change of 2.55%, 15.09%, and 8.65% for cervical,
      thoracic inlet, and intra-thoracic tracheal diameters, respectively. Initial mean
      stent length was 26.72% higher than nominal length and ultimate long-term
      tracheal mean stent shortening was only 9.90%. No significant stent migration was
      identified in the immediate, short-, or long-term periods. Good inter-observer
      agreement of radiographic measurements was found among observers of variable
      experience level. CONCLUSIONS AND CLINICAL IMPORTANCE: Use of an intraluminal
      tracheal stent for CTCS is associated with minimal stent shortening with no
      clinically relevant stent migration after fluoroscopic placement. Precise stent
      sizing and placement techniques likely play important roles in avoiding these
      reported complications.

PMID- 29460369
TI  - Drought timing and local climate determine the sensitivity of eastern temperate
      forests to drought.
AB  - Projected changes in temperature and drought regime are likely to reduce carbon
      (C) storage in forests, thereby amplifying rates of climate change. While such
      reductions are often presumed to be greatest in semi-arid forests that experience
      widespread tree mortality, the consequences of drought may also be important in
      temperate mesic forests of Eastern North America (ENA) if tree growth is
      significantly curtailed by drought. Investigations of the environmental
      conditions that determine drought sensitivity are critically needed to accurately
      predict ecosystem feedbacks to climate change. We matched site factors with the
      growth responses to drought of 10,753 trees across mesic forests of ENA,
      representing 24 species and 346 stands, to determine the broad-scale drivers of
      drought sensitivity for the dominant trees in ENA. Here we show that two factors
      the timing of drought, and the atmospheric demand for water (i.e., local
      potential evapotranspiration; PET)-are stronger drivers of drought sensitivity
      than soil and stand characteristics. Drought-induced reductions in tree growth
      were greatest when the droughts occurred during early-season peaks in radial
      growth, especially for trees growing in the warmest, driest regions (i.e.,
      highest PET). Further, mean species trait values (rooting depth and psi50 ) were
      poor predictors of drought sensitivity, as intraspecific variation in sensitivity
      was equal to or greater than interspecific variation in 17 of 24 species. From a
      general circulation model ensemble, we find that future increases in early-season
      PET may exacerbate these effects, and potentially offset gains in C uptake and
      storage in ENA owing to other global change factors.

PMID- 29460370
TI  - The association between team-level social capital and individual-level work
      engagement: Differences between subtypes of social capital and the impact of
      intra-team agreement.
AB  - The study explored the association between team-level social capital and
      individual-level work engagement. Questionnaire data were collected from six
      companies in the dairy industry. Seven hundred seventy-two participants divided
      into 65 teams were included. In confirmatory factor analyses, we found a superior
      model fit to a four dimensional model of social capital: bonding social capital,
      bridging social capital and two types of linking social capital. The results
      showed a positive association between all subtypes of social capital at the team
      level and work engagement at the individual level. However, this association only
      remained significant for linking social capital in relation the workplace as a
      whole when we adjusted for psychosocial working conditions. The level of intra
      team agreement in social capital score did not moderate the association between
      social capital and work engagement. In conclusion, the results provide further
      support for previous findings suggesting a positive association between social
      capital and work engagement. They add to the existing knowledge by suggesting
      that linking social capital in relation to the workplace is the most important
      explanatory variable for work engagement, thus emphasizing the need to
      distinguish between subtypes of social capital in research and practice.

PMID- 29460371
TI  - Uploading cellular batteries: Caring for mitochondria is key.

PMID- 29460373
TI  - Examining regional variability in work ethic within Mexico: Individual difference
      or shared value.
AB  - Despite the acceptance of work ethic as an important individual difference,
      little research has examined the extent to which work ethic may reflect shared
      environmental or socio-economic factors. This research addresses this concern by
      examining the influence of geographic proximity on the work ethic experienced by
      254 employees from Mexico, working in 11 different cities in the Northern,
      Central and Southern regions of the country. Using a sequence of complementary
      analyses to assess the main source of variance on seven dimensions of work ethic,
      our results indicate that work ethic is most appropriately considered at the
      individual level.

PMID- 29460372
TI  - Effects of a rice diet and phytase addition on growth performance, tissue
      weights, phosphorus and nitrogen retention, and on liver threonine dehydrogenase,
      malic enzyme and fatty acid synthase activities in broiler chicks.
AB  - This experiment was conducted to clarify the nutritional functions of rice and
      phytase addition for broiler chicks. Thirty-six 7-day-old male chicks (ROSS 308
      strain) were assigned to one of the four treatment groups: corn- or rice-based
      diet groups and each diet with added phytase (2000 phytase units/kg diet) groups
      (corn + P or rice + P groups). The non-phytate phosphorus (npP) content in the
      diets with added phytase was approximately half of the requirement. Body weight
      gain and feed intake in the rice group was significantly higher than those in the
      corn group. Breast and thigh muscle weights and nitrogen retention in the rice
      group were significantly higher than that in the corn group. Although the
      efficiency of phosphorus retention (%) in the corn + P group was significantly
      higher than that in the corn group, no significant difference was observed
      between the rice and rice + P groups. Liver threonine dehydrogenase activity in
      the corn group was significantly higher than in the other three groups. These
      results indicate that rice is superior to corn as a starter diet in broiler
      chicks, and that phytase action in the rice-based diet was less than that in the
      corn-based diet.

PMID- 29460374
TI  - Del Nido cardioplegia for minimally invasive aortic valve replacement.
AB  - BACKGROUND: We analyzed the impact and safety of del Nido Cardioplegia (DNC) in
      patients undergoing minimally invasive aortic valve replacement (MIAVR). METHODS:
      We analyzed all isolated MIAVR replacements from 5/2013-6/2015 excluding re
      operative patients. The approach was a hemi-median sternotomy in all patients.
      Patients were divided into two cohorts, those who received 4:1 crystalloid:blood
      DNC solution and those in whom standard 1:4 Buckberg-based cardioplegia (WBC) was
      used. One-to-one propensity case matching of DNC to WBC was performed based on
      standard risk factors and differences between groups were analyzed using chi
      square and non-parametric methods. RESULTS: MIAVR was performed in 181 patients;
      DNC was used in 59 and WBC in 122. Case matching resulted in 59 patients per
      cohort. DNC was associated with reduced re-dosing (5/59 (8.5%) versus 39/59
      (61.0%), P < 0.001) and less total cardioplegia volume (1290 +/- 347 mL vs 2284
      +/- 828 mL, P < 0.001). Antegrade cardioplegia alone was used in 89.8% (53/59) of
      DNC patients versus 33.9% (20/59) of WBC patients (P < 0.001). Median bypass and
      aortic cross-clamp times were similar. Clinical outcomes were similar with
      respect to post-operative hematocrit, transfusion requirements, need for
      inotropic/pressor support, duration of intensive care unit stay, re-intubation,
      length of stay, new onset atrial fibrillation, and mortality. CONCLUSIONS: Del
      Nido cardioplegia usage during MIAVR minimized re-dosing and the need for
      retrograde delivery. Patient safety was not compromised with this technique in
      this group of low-risk patients undergoing MIAVR.

PMID- 29460376
TI  - Large Negative Differential Resistance and Rectification from a Donor-sigma
      Acceptor Molecule in the Presence of Dissimilar Electrodes.
AB  - A multifunctional spin quantum device obtained by sandwiching 11-mercaptoundeca
      2,4,8,10-tetraenenitrile, a donor-sigma-acceptor molecule, between gold and iron
      electrodes is proposed. The device can act as a spin rectifier at lower bias and
      also exhibits negative differential resistance (NDR) after attaining a bias of
      1.3 V. The rectification feature is quite prominent in the spin-up channel, with
      an appreciable rectification ratio of 68, whereas the NDR indicator, that is, the
      peak to valley ratio (~10) of the current-voltage characteristics after 1.3 V, is
      also quite significant. To understand the origin of this in silico observation,
      nonequilibrium green's function based DFT calculations have been performed.
      Analyses reveal that both properties originate from the bias-independent energy
      offset between the frontier orbitals and electrode Fermi levels, popularly known
      as Fermi-level pinning. More precisely, rectification results from the Fermi
      level pinning of the HOMO and LUMO with the gold and iron electrodes,
      respectively; the Fermi-level pinning forces a HOMO-LUMO crossover that helps to
      explain the origin of the NDR.

PMID- 29460375
TI  - Periodontal education and assessment in the undergraduate dental curriculum-A
      questionnaire-based survey in European countries.
AB  - OBJECTIVES: This survey aimed to evaluate whether periodontal education and
      assessment in undergraduate dental curricula amongst the member countries of the
      European Federation of Periodontology (EFP) follow the competency-based
      curricular guidelines and recommendations developed by the Association for Dental
      Education in Europe. MATERIALS AND METHODS: A multiple-choice questionnaire was
      emailed to 244 dental institutes amongst the 24 EFP member countries between
      November 2014 and July 2015. RESULTS: Data were received from 16 (66.7%) EFP
      member countries. Out of 117 responding dental institutes, 76 (64.95%) were
      included as valid responders. In most of the institutes (86.3%), a minimum set of
      competencies in periodontology was taken into account when constructing their
      dental education programmes. Out of 76 responders, 98.1% included lecture-based,
      74.1% case-based and 57.1% problem-based teaching in their periodontal curricula,
      whilst a minority (15.9%) also used other methods. A similar pattern was also
      seen in the time allocation for these four educational methods, that is, the
      highest proportion (51.8%) was dedicated to lecture-based teaching and only a
      small proportion (5.7%) to other methods. Periodontal competencies and skills
      were most frequently assessed by clinical grading on clinic, multiple-choice
      examination (written examination) and oral examination, whereas competency tests
      and self-assessment were rarely used. Only in 11 (14.5%) cases, access flap
      procedures were performed by students. CONCLUSION: Great diversity in teaching
      methodology amongst the surveyed schools was demonstrated, and thus, to harmonise
      undergraduate periodontal education and assessment across Europe, a minimum set
      of recommendations could be developed and disseminated by the EFP.

PMID- 29460377
TI  - Obstetric providers willing to accept women's preferences for mode of delivery.

PMID- 29460378
TI  - Bone mineral density and body composition in children with congenital adrenal
      hyperplasia.
AB  - OBJECTIVE: Children with congenital adrenal hyperplasia (CAH) are exposed to
      fluctuating cortisol and androgen levels. The effects these hormonal states have
      on bone mineral density (BMD) and body composition are not well studied. The
      study's objective was to compare BMD and body composition, including visceral
      adipose tissue (VAT) and Android:Gynoid (A:G) ratio, in children with CAH vs
      healthy age-matched, sex-matched and BMI-matched controls. DESIGN: Total body BMD
      (TBMD) Z-scores were adjusted for height-for-age Z-scores (TBMDHAZ).
      Hydrocortisone dose (mg/m2/d) was averaged over the past year. Bone age Z-scores
      were used as a surrogate for long-term androgen exposure in cases. Statistical
      analyses comparing cases and controls accounted for matched groups using mixed
      linear models. PATIENTS: Forty-two cases with CAH (average age 12.3 years [SE 3];
      17 males) and 101 controls underwent a dual-energy X-ray absorptiometry scan.
      RESULTS: Children with CAH had lower TBMD (0.81 vs 1.27, P = .003) and TBMDHAZ Z
      scores (-0.51 vs -0.01, P = .001) than controls. In CAH cases, TBMD and TBMDHAZ Z
      scores were positively correlated with bone age Z-scores (r = .63, P < .0001; r =
      .51, P = .001, respectively) but were not associated with HC dose. VAT and the
      A:G ratio did not differ significantly between children with CAH and controls and
      neither was associated with HC dose.VAT was not associated with bone age Z-score.
      CONCLUSION: Lower BMD was observed in CAH cases compared with controls although
      no differences in body composition were identified. Among CAH cases, increased
      chronic androgen exposure, as measured by bone age Z-scores, was associated with
      higher BMD but was not associated with VAT.

PMID- 29460379
TI  - Five-year long-term clinical outcome after bariatric metabolic surgery: A multi
      ethnic Asian population in Singapore.
AB  - Bariatric surgery is an effective treatment for morbid obesity and its metabolic
      related comorbidities; type 2 diabetes, hypertension and hyperlipidaemia.1
      However, the literature is scarce regarding the long-term outcome after bariatric
      surgery, especially among multi-ethnic Asian populations. Considering the growing
      number of bariatric metabolic surgeries in Asia, we have attempted to provide a
      regional perspective on 5-year long-term clinical outcomes post bariatric surgery
      in Singapore. Between 2010 and 2016, all bariatric operative cases were included,
      and these comprised: laparoscopic sleeve gastrectomy (LSG), 393; laparoscopic
      Roux-En-Y gastric bypass (RYGB), 125; laparoscopic mini-gastric bypass (MGB), 43.
      The primary outcome measure was the percentage of excess weight loss (% EWL) at 6
      months, 1, 2, 3, 4 and 5 years, with % remission of type 2 diabetes mellitus
      (T2DM) at 1 year following LSG (49.7%, 61.2%, 56.1%, 47.8%, 40.8% and 47.3%;
      82.2%), RYGB (60.2%, 62.1%, 57.6%, 50.1%, 48.7% and 47.7%; 86.9%) and MGB (58%,
      68.1%, 62.7%, 66.2%, 64.0%, 65.2%; 71.9%). In conclusion, MGB and RYGB showed the
      greatest % EWL at 5 years and are recommended for moderate T2DM. LSG is an
      effective bariatric operation with a high % EWL up to 2 years, and a high
      remission rate of mild T2DM. The remission rate of T2DM was equally high in all 3
      surgical groups, independent of ethnic differences.

PMID- 29460380
TI  - Iron-Catalyzed Cross-Couplings in the Synthesis of Pharmaceuticals: In Pursuit of
      Sustainability.
AB  - The scarcity of precious metals has led to the development of sustainable
      strategies for metal-catalyzed cross-coupling reactions. The establishment of new
      catalytic methods using iron is attractive owing to the low cost, abundance,
      ready availability, and very low toxicity of iron. In the last few years,
      sustainable methods for iron-catalyzed cross-couplings have entered the critical
      area of pharmaceutical research. Most notably, iron is one of the very few metals
      that have been successfully field-tested as highly effective base-metal catalysts
      in practical, kilogram-scale industrial cross-couplings. In this Minireview, we
      critically discuss the strategic benefits of using iron catalysts as green and
      sustainable alternatives to precious metals in cross-coupling applications for
      the synthesis of pharmaceuticals. The Minireview provides an essential
      introduction to the fundamental aspects of practical iron catalysis, highlights
      areas for improvement, and identifies new fields to be explored.

PMID- 29460381
TI  - The Development of Empathic Concern in Siblings: A Reciprocal Influence Model.
AB  - This study utilized actor-partner interdependence modeling to examine the
      bidirectional effects of younger (Mage  = 18 months) and older siblings (Mage  =
      48 months) on later empathy development in a large (n = 452 families), diverse
      (42% immigrant) Canadian sample. Controlling for parenting, demographic
      characteristics, sibling relationship quality, and within-child stability in
      empathic concern, both younger and older siblings' observed empathic concern
      uniquely predicted relative increases in the other's empathy over a period of 18
      months. The strength of the partner effects did not differ by birth order. Sex
      composition moderated the younger sibling partner effect, whereas age gap
      moderated the older sibling partner effect. This study highlights the important
      role that siblings play in enhancing the development of care and concern for
      others.

PMID- 29460382
TI  - An algorithm for predicting Robin sequence from fetal MRI.
AB  - BACKGROUND: Infants with Robin sequence (RS) may present with airway compromise
      at delivery. Prenatal diagnosis would improve preparation and postnatal care. The
      purpose of this study was to devise a predictive algorithm for RS based on fetal
      magnetic resonance imaging (MRI). METHODS: Retrospective case-control study
      including fetal MRIs from 2002 to 2017. Inclusion criteria were (1) MRI of
      adequate quality, (2) live-born infant, and (3) postnatal evaluation. Subjects
      were grouped on the basis of postnatal diagnosis: (1) RS (micrognathia,
      glossoptosis, airway obstruction), (2) micrognathia without airway obstruction
      ("micrognathia"), (3) cleft lip and palate ("CLP"), and (4) gestational age
      matched controls. A series of possible predictive variables were assessed on MRI.
      Receiver operator curves were applied to identify cut-off values, and a
      multivariable algorithm was developed. RESULTS: A total of 162 subjects with mean
      gestational age at MRI of 25.6 +/- 4.9 weeks were included: RS, n = 27 (17%);
      micrognathia, n = 35 (22%); CLP, n = 46 (28%); control, n = 54 (33%). Three
      variables were independent predictors of RS: (1) Veau I/II cleft palate (OR =
      38.8), (2) tongue shape index (>80%; OR = 8.7), and (3) inferior facial angle
      (<48 degrees ; OR = 14.5). CONCLUSION: MRI findings of cleft palate, TSI >80% and
      IFA <48 degrees  indicate a 98% probability of RS, whereas a lack of all 3
      features denotes a likelihood of 1%.

PMID- 29460383
TI  - Using permutation tests to enhance causal inference in interrupted time series
      analysis.
AB  - RATIONALE, AIMS AND OBJECTIVES: Interrupted time series analysis (ITSA) is an
      evaluation methodology in which a single treatment unit's outcome is studied
      serially over time and the intervention is expected to "interrupt" the level
      and/or trend of that outcome. The internal validity is strengthened considerably
      when the treated unit is contrasted with a comparable control group. In this
      paper, we introduce a robustness check based on permutation tests to further
      improve causal inference. METHOD: We evaluate the effect of California's
      Proposition 99 for reducing cigarette sales by iteratively casting each
      nontreated state into the role of "treated," creating a comparable control group
      using the ITSAMATCH package in Stata, and then evaluating treatment effects using
      ITSA regression. If statistically significant "treatment effects" are estimated
      for pseudotreated states, then any significant changes in the outcome of the
      actual treatment unit (California) cannot be attributed to the intervention. We
      perform these analyses setting the cutpoint significance level to P > .40 for
      identifying balanced matches (the highest threshold possible for which controls
      could still be found for California) and use the difference in differences of
      trends as the treatment effect estimator. RESULTS: Only California attained a
      statistically significant treatment effect, strengthening confidence in the
      conclusion that Proposition 99 reduced cigarette sales. CONCLUSIONS: The proposed
      permutation testing framework provides an additional robustness check to either
      support or refute a treatment effect identified in for the true treated unit in
      ITSA. Given its value and ease of implementation, this framework should be
      considered as a standard robustness test in all multiple group interrupted time
      series analyses.

PMID- 29460384
TI  - Quantum-rotor-induced polarization.
AB  - Quantum-rotor-induced polarization is closely related to para-hydrogen-induced
      polarization. In both cases, the hyperpolarized spin order derives from
      rotational interaction and the Pauli principle by which the symmetry of the
      rotational ground state dictates the symmetry of the associated nuclear spin
      state. In quantum-rotor-induced polarization, there may be several spin states
      associated with the rotational ground state, and the hyperpolarization is
      typically generated by hetero-nuclear cross-relaxation. This review discusses
      preconditions for quantum-rotor-induced polarization for both the 1-dimensional
      methyl rotor and the asymmetric rotor H217 O@C60 , that is, a single water
      molecule encapsulated in fullerene C60 . Experimental results are presented for
      both rotors.

PMID- 29460386
TI  - Amino acid racemization and its relation to geochronology and archaeometry.
AB  - Amino acid racemization, used as a method of relative and quantitative dating of
      fossils, evaluates the degree of postmortem conversion of l to d amino acid
      enantiomers. While extensively utilized, this method has garnered confusion due
      to controversial age estimates for human fossils in North America in the 1970s.
      This paper explains the age controversy and aftermath, current chromatographic
      methods used in research, mathematical calibration models, and a short synopsis
      of other dating techniques in geochronology and archaeometry.

PMID- 29460385
TI  - Primary non-adherence and the new-user design.

PMID- 29460387
TI  - Optimizing Water Exchange Rates and Rotational Mobility for High-Relaxivity of a
      Novel Gd-DO3A Derivative Complex Conjugated to Inulin as Macromolecular Contrast
      Agents for MRI.
AB  - Thanks to the understanding of the relationships between the residence lifetime
      tauM of the coordinated water molecules to macrocyclic Gd-complexes and the
      rotational mobility tauR of these structures, and according to the theory for
      paramagnetic relaxation, it is now possible to design macromolecular contrast
      agents with enhanced relaxivities by optimizing these two parameters through
      ligand structural modification. We succeeded in accelerating the water exchange
      rate by inducing steric compression around the water binding site, and by
      removing the amide function from the DOTA-AA ligand [1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid mono(p-aminoanilide)] (L)
      previously designed. This new ligand 10[2(1-oxo-1-p-propylthioureidophenylpropyl]
      1,4,7,10-tetraazacyclodecane-1,4,7-tetraacetic acid (L1 ) was then covalently
      conjugated to API [O-(aminopropyl)inulin] to get the complex API-(GdL1 )x with
      intent to slow down the rotational correlation time (tauR ) of the macromolecular
      complex. The evaluation of the longitudinal relaxivity at different magnetic
      fields and the study of the 17 O-NMR at variable temperature of the low-molecular
      weight compound (GdL1 ) showed a slight decrease of the tauM value (tauM310 = 331
      ns vs. tauM310 = 450 ns for the GdL complex). Consequently to the increase of the
      size of the API-(GdL1 )x complex, the rotational correlation time becomes about
      360 times longer compared to the monomeric GdL1 complex (tauR  = 33,700 ps),
      which results in an enhanced proton relaxivity.

PMID- 29460388
TI  - Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate
      in women and girls with hereditary factor X deficiency.
AB  - : Essentials Plasma-derived factor X concentrate (pdFX) is used to treat
      hereditary factor X deficiency. pdFX pharmacokinetics, safety and efficacy were
      assessed in factor X-deficient women/girls. Treatment success rate was 98%; only
      6 adverse events in 2 subjects were possibly pdFX related. On-demand pdFX 25 IU
      kg-1 was effective and safe in women/girls with factor X deficiency. SUMMARY:
      Background A high-purity, plasma-derived factor X concentrate (pdFX) has been
      approved for the treatment of hereditary FX deficiency, an autosomal recessive
      disorder. Objective To perform post hoc assessments of pdFX pharmacokinetics,
      safety and efficacy in women and girls with hereditary FX deficiency.
      Patients/Methods Subjects aged >= 12 years with moderate/severe FX deficiency
      (plasma FX activity of < 5 IU dL-1 ) received on-demand or preventive pdFX (25 IU
      kg-1 ) for <= 2 years. Results Of 16 enrolled subjects, 10 women and girls (aged
      14-58 years [median, 25.5 years]) received 267 pdFX infusions. Mean monthly
      infusions per subject were higher among women and girls (2.48) than among men and
      boys (1.62). In women and girls, 132 assessable bleeding episodes (61 heavy
      menstrual bleeds, 47 joint bleeds, 15 muscle bleeds, and nine other bleeds) were
      treated with pdFX, with a 98% treatment success rate versus 100% in men and boys.
      Mean pdFX incremental recovery was similar in the two groups (2.05 IU dL-1 versus
      1.91 IU dL-1 per IU kg-1 ), as was the mean half-life (29.3 h versus 29.5 h). Of
      142 adverse events in women and girls, headache was the most common (12 events in
      six subjects). Six events (two infusion-site erythema, two fatigue, one back
      pain, one infusion-site pain) in two subjects were considered to be possibly pdFX
      related. Following the trial, pdFX was used to successfully maintain hemostasis
      in two subjects undergoing obstetric delivery. Conclusions pdFX was well
      tolerated and effective in women and girls with FX deficiency. Although women and
      girls had different bleeding symptoms and sites than men and boys, their pdFX
      pharmacokinetic profile was comparable.

PMID- 29460389
TI  - The remarkable vocal anatomy of the koala (Phascolarctos cinereus): insights into
      low-frequency sound production in a marsupial species.
AB  - Koalas are characterised by a highly unusual vocal anatomy, with a descended
      larynx and velar vocal folds, allowing them to produce calls at
      disproportionately low frequencies. Here we use advanced imaging techniques,
      histological data, classical macroscopic dissection and behavioural observations
      to provide the first detailed description and interpretation of male and female
      koala vocal anatomy. We show that both males and females have an elongated
      pharynx and soft palate, resulting in a permanently descended larynx. In
      addition, the hyoid apparatus has a human-like configuration in which paired
      dorsal, resilient ligaments suspend the hyoid apparatus from the skull, while the
      ventral parts tightly connect to the descended larynx. We also show that koalas
      can retract the larynx down into the thoracic inlet, facilitated by a dramatic
      evolutionary transformation of the ventral neck muscles. First, the usual
      retractors of the larynx and the hyoid have their origins deep in the thorax.
      Secondly, three hyoid muscles have lost their connection to the hyoid skeleton.
      Thirdly, the genioglossus and geniohyoid muscles are greatly increased in length.
      Finally, the digastric, omohyoid and sternohyoid muscles, connected by a common
      tendinous intersection, form a guiding channel for the dynamic down-and-up
      movements of the ventral hyoid parts and the larynx. We suggest that these
      features evolved to accommodate the low resting position of the larynx and assist
      in its retraction during call production. We also confirm that the edges of the
      intra-pharyngeal ostium have specialised to form the novel, extra-laryngeal velar
      vocal folds, which are much larger than the true intra-laryngeal vocal folds in
      both sexes, but more developed and specialised for low frequency sound production
      in males than in females. Our findings illustrate that strong selection pressures
      on acoustic signalling not only lead to the specialisation of existing vocal
      organs but can also result in the evolution of novel vocal structures in both
      sexes.

PMID- 29460390
TI  - Safety assessment, biological effects, and mechanisms of Myrica rubra fruit
      extract for anti-melanogenesis, anti-oxidation, and free radical scavenging
      abilities on melanoma cells.
AB  - OBJECTIVE: Currently, the cosmetic and medical industries are paying considerable
      attention to solve or prevent skin damage or diseases, such as hyperpigmentation
      and oxidation and free radical damage. In this study, the effective compounds in
      Myrica rubra fruit were extracted and studied the biological effects of these M.
      rubra fruit extracts. METHODS: In this study, we extracted M. rubra fruit using
      solutions with various ratios of water to ethanol (100:0, 50:50, 5:95) and
      studied the anti-melanogenesis, anti-oxidation and radical scavenging effects of
      these M. rubra fruit extracts on two melanoma cell lines: mouse melanoma (B16-F0)
      and human melanoma (A2058). The cytotoxicity, melanin synthesis, mushroom and
      cellular tyrosinase activities, enzyme kinetics, melanogenesis-related gene
      expression, melanogenesis-related protein secretion, radical DPPH scavenging
      activity and ROS inhibition after treatment with M. rubra fruit extracts were
      determined. RESULTS: The results showed that the water extract of M. rubra fruit
      was less cytotoxic to the melanoma cell lines, effectively inhibited melanin
      synthesis and tyrosinase activity and down-regulated the gene expression and
      protein secretion of MITF and TRP-1. In addition, the M. rubra fruit extracts
      also showed the abilities to scavenge DPPH free radicals and suppress ROS
      production. Finally, the effective compounds in the water extract were Myricetin
      O-deoxyhexoside, Quercetin-O-deoxyhexoside, and Kaempferol-O-hexoside determined
      by LC/MS/MS assay. CONCLUSION: Overall, the water extract of M. rubra fruit is a
      safe and effective melanin inhibitor and anti-oxidant and can be applied widely
      in the fields of cosmetics and medicine.

PMID- 29460391
TI  - Counting the Clicks in Fluorescent Polymer Networks.
AB  - We introduce a fluorescence-based methodology enabling the quantification of
      ligation points in photochemically prepared polymer networks. Well-defined
      alpha,omega-tetrazole-capped polymer strands prepared via RAFT polymerization are
      crosslinked under UV irradiation by a trimaleimide via nitrile imine mediated
      tetrazole-ene cycloaddition. Thus, for each linkage point a fluorescent
      pyrazoline ring is formed, resulting in fluorescent networks, which are
      degradable by aminolysis of the trithiocarbonate functionalities, leading to
      soluble fragments. The fluorescence emission of the soluble network fragments
      correlates directly with the number of pyrazoline moieties originally present in
      the network, thus providing a direct measure of the number of ligation points
      constituting the network. The herein introduced strategy based on a fluorescence
      readout is a powerful yet simple approach to quantify network formation processes
      applicable to a wide class of polymers accessible via RAFT.

PMID- 29460394
TI  - Preface.

PMID- 29460395
TI  - Proceedings of International Conference on Cell Death in Cancer and Toxicology.
      February 20-22, 2018. Guest Editors: Kausar M. Ansari, CSIR-IITR, India and Dhyan
      Chandra, Roswell Park, USA.

PMID- 29460393
TI  - Embryo-fetal development studies with the dietary supplement vinpocetine in the
      rat and rabbit.
AB  - Dietary supplement and natural product use is increasing within the United
      States, resulting in growing concern for exposure in vulnerable populations,
      including young adults and women of child-bearing potential. Vinpocetine is a
      semisynthetic derivative of the Vinca minor extract, vincamine. Human exposure to
      vinpocetine occurs through its use as a dietary supplement for its purported
      nootropic and neuroprotective effects. To investigate the effects of vinpocetine
      on embryo-fetal development, groups of 25 pregnant Sprague-Dawley rats and 8
      pregnant New Zealand White rabbits were orally administered 0, 5, 20, or 60 mg
      vinpocetine/kg and 0, 25, 75, 150, or 300 mg/kg daily from gestational day (GD) 6
      20 and GD 7-28, respectively. Pregnant rats dosed with vinpocetine demonstrated
      dose-dependent increases in postimplantation loss, higher frequency of early and
      total resorptions, lower fetal body weights, and fewer live fetuses following
      administration of 60 mg/kg, in the absence of maternal toxicity. Additionally,
      the rat fetuses displayed dose-dependent increases in the incidences of
      ventricular septum defects and full supernumerary thoracolumbar ribs. Similarly,
      albeit at higher doses than the rats, pregnant rabbits administered vinpocetine
      displayed an increase in postimplantation loss and fewer live fetuses (300
      mg/kg), in addition to significantly lower fetal body weights (>=75 mg/kg). In
      conclusion, vinpocetine exposure resulted in similar effects on embryo-fetal
      development in the rat and rabbit. The species differences in sensitivity and
      magnitude of response is likely attributable to a species difference in
      metabolism. Taken together, these data suggest a potential hazard for pregnant
      women who may be taking vinpocetine.

PMID- 29460396
TI  - Lower sperm quality and testicular and epididymal structural impairment in adult
      rats exposed to rosuvastatin during prepuberty.
AB  - The increase of obesity, bad eating habits and the lack of physical exercises are
      highly related to dyslipidemias. Rosuvastatin is a lipid-lowering drug and has
      been indicated to prevent cardiovascular diseases and to treat dyslipidemias due
      to its higher efficiency to reduce serum cholesterol concentrations. This study
      aimed to evaluate the reproductive adverse effects on sexual maturity due to
      rosuvastatin exposure in juvenile male rats during prepuberty. Three groups were
      randomly formed with newly weaned rats: control, whose rats received saline
      solution 0.9% and rosuvastatin at doses of 3 or 10 mg kg-1 day-1 , administered
      orally by gavage, from postnatal day 21 until preputial separation (average of 45
      days for controls and 49 days for statin-treated animals), indicative of puberty
      onset. Male rats were maintained until sexual maturity and were killed on
      postnatal day 110. In the rosuvastatin-treated groups, the results showed
      diminished follicle-stimulating hormone, luteinizing hormone and testosterone
      concentrations, increased estradiol and prolactin concentrations, histopathologic
      alterations on testis and epididymis and decreased sperm quality. Moreover,
      statin-exposed groups showed decreased expression of androgen receptor on testis
      and epididymis and lower expression of aquaporin-9 on epididymal epithelium. In
      conclusion, administration of rosuvastatin to prepubertal male rats provoked long
      term hormonal deregulation and impaired reproduction at adulthood.

PMID- 29460397
TI  - Reporting quality of trial abstracts-improved yet suboptimal: A systematic review
      and meta-analysis.
AB  - OBJECTIVES: We conducted a systematic review and meta-analysis of literature to
      determine if the publication of the Consolidated Standards of Reporting Trials
      (CONSORT) abstract guideline in 2008 was followed by change in reporting quality
      of randomized controlled trial (RCT) abstracts. STUDY DESIGN AND SETTINGS:
      Evaluations were included if they compared reporting quality of RCT abstracts
      before and after the publication of CONSORT-abstract guideline. The literature
      search was performed (January 2008 to April 2017) in Medline (Ovid), EMbase,
      CINAHL plus and Cochrane methodologies register. We assessed study validity with
      a special validity tool, adapted from a previous Cochrane review. RESULTS:
      Initial search identified 4142 articles, of which total 10 evaluations including
      5184 abstracts were included. Total 22 outcomes related to individual items of
      CONSORT-abstract guideline were assessed, and 14 showed significant effect sizes
      favoring CONSORT-abstract guideline. Despite significant effect size, the overall
      post-CONSORT reporting (PCR) was suboptimal for ten items: title (RR = 1.40, 95%
      CI 1.23 to 1.59, PCR = 53.4%), participants (RR = 1.58, 95% CI 1.11 to 2.26, PCR
      = 24.5%), primary outcome (RR = 1.12, 95% CI 1.02 to 1.23, PCR = 65%), blinding
      (RR = 2.13, 95% CI 1.20 to 3.76, PCR = 13.9%), trial status (RR = 1.81, 95% 1.39
      to 2.35, PCR = 10.6%), numbers analyzed (RR = 1.51, 95% CI 1.15 to 1.98, PCR =
      26.5%), outcome (RR = 1.40, 95% 1.05 to 1.86, PCR = 21.9%), effect size and
      precision (RR = 1.59, 95% CI 1.15 to 2.19, PCR = 58.9%), harms (RR = 1.24, 95% CI
      1.04 to 1.48, PCR = 41.8%), trial registration (RR = 2.02, 95% CI 1.63 to 2.50,
      PCR = 33.8%). Three items with favorable effect size in addition had wide CIs:
      randomization (RR = -4.28, 95% CI 1.56 to 11.75, PCR = -3.3%), allocation
      concealment (RR = -19.89, 95% CI 1.54 to 256.69, PCR = -5.7%), and funding (RR = 
      22.61, 95% CI 8.13 to 62.67, PCR = -11.32%). CONCLUSION: The change in reporting
      quality of RCT abstracts is far from satisfactory, as evidenced by suboptimal
      post-CONSORT rates and wide CIs of effect sizes for majority of improved items.
      Mere publication of CONSORT-abstract guideline, without strict endorsement has
      failed to translate into good quality abstracts.

PMID- 29460399
TI  - Recent Progress in the Development of Conducting Polymer-Based Nanocomposites for
      Electrochemical Biosensors Applications: A Mini-Review.
AB  - Among various immobilizing materials, conductive polymer-based nanocomposites
      have been widely applied to fabricate the biosensors, because of their
      outstanding properties such as excellent electrocatalytic activity, high
      conductivity, and strong adsorptive ability compared to conventional conductive
      polymers. Electrochemical biosensors have played a significant role in delivering
      the diagnostic information and therapy monitoring in a rapid, simple, and low
      cost portable device. This paper reviews the recent developments in conductive
      polymer-based nanocomposites and their applications in electrochemical
      biosensors. The article starts with a general and concise comparison between the
      properties of conducting polymers and conducting polymer nanocomposites. Next,
      the current applications of conductive polymer-based nanocomposites of some
      important conducting polymers such as PANI, PPy, and PEDOT in enzymatic and
      nonenzymatic electrochemical biosensors are overviewed. This review article
      covers an 8-year period beginning in 2010.

PMID- 29460398
TI  - Centralization errors in comparative genomic hybridization array analysis of
      pituitary tumor samples.
AB  - Reliable interpretation of comparative genomic hybridization array (aCGH) results
      requires centralization and normalization of the data. We evaluated the
      reliability of aCGH centralization by comparing aCGH results (with classical
      centralization-normalization steps) to fluorescence in situ hybridization (FISH)
      results. In addition, we propose a method to correct centralization bias. Sixty
      six pituitary tumors were analyzed (Agilent aCGH + SNP 4 * 180K microarray). For
      each tumor, the FISH-based log2 (ratios) of a subset of chromosomes were compared
      with the corresponding aCGH raw log2 (ratios). With our new normalization
      centralization process, this difference was added to all log2 (ratios), before
      performing loess regression on non-altered probes only. Finally, the mean log2
      (ratio) and the percentage of normal probes were compared between CGHnormaliter
      and our new FISH-based method. For 11 tumors, FISH results and raw CGH log2
      (ratios) differed significantly. In addition, nine tumors showed discrepancies
      between results generated by CGHnormaliter and our new-method. Such discrepancies
      seemed to occur with tumours with many abnormalities (0%-40% normal probes),
      rather than in those tumours with fewer abnormalities (31%-100% normal probes).
      Five tumors had too few normal probes to allow normalization. In these tumors,
      which can exhibit many changes in DNA copy number, we found that centralization
      bias was frequent and uncorrected by current normalization methods. Therefore, an
      external control for centralization, such as FISH analysis, is required to insure
      reliable interpretation of aCGH data.

PMID- 29460400
TI  - Self-Assembled Peptide-Based Nanomaterials for Biomedical Imaging and Therapy.
AB  - Peptide-based materials are one of the most important biomaterials, with diverse
      structures and functionalities. Over the past few decades, a self-assembly
      strategy is introduced to construct peptide-based nanomaterials, which can form
      well-controlled superstructures with high stability and multivalent effect. More
      recently, peptide-based functional biomaterials are widely utilized in clinical
      applications. However, there is no comprehensive review article that summarizes
      this growing area, from fundamental research to clinic translation. In this
      review, the recent progress of peptide-based materials, from molecular building
      block peptides and self-assembly driving forces, to biomedical and clinical
      applications is systematically summarized. Ex situ and in situ constructed
      nanomaterials based on functional peptides are presented. The advantages of
      intelligent in situ construction of peptide-based nanomaterials in vivo are
      emphasized, including construction strategy, nanostructure modulation, and
      biomedical effects. This review highlights the importance of self-assembled
      peptide nanostructures for nanomedicine and can facilitate further knowledge and
      understanding of these nanosystems toward clinical translation.

PMID- 29460401
TI  - Reply to 'Comment on "Use of antibiotics during pregnancy and the risk of major
      congenital malformations: a population based cohort study" by Muanda et al.'

PMID- 29460402
TI  - What can dental education gain by understanding student experience of the
      curriculum?
AB  - INTRODUCTION: Within higher education, there is increasing recognition that
      understanding the ways students experience the educational environment is
      critical to developing programmes that can educate our future professionals.
      There is a small body of literature about how students experience the dental
      educational environment; however, none that adopts a qualitative phenomenographic
      approach. This study aims to contribute to our understanding by asking what is
      the variation in the ways dental students experience their curriculum? METHODS:
      This study uses a phenomenographic methodology. Phenomenography investigates the
      variation in the way a group of people experience a situation, and how they
      ascribe meaning to it. Interviews were conducted with 14 senior dental students
      at the University of Sydney. Transcripts were analysed using a phenomenographic
      approach. RESULTS: Six increasingly sophisticated, qualitatively distinct
      categories of description were identified from the collective of transcripts:
      surviving the education system; following a guide or manual, learning how to
      treat teeth, learning how to meet patient treatment needs, learning how to relate
      with patients and understanding the complexities of dental practice. The outcome
      space consists of ways the categories of description are related; considering
      interactions with teachers, ways of coping with multiple opinions and integration
      of disciplinary learning. CONCLUSION: This study provides new insights into the
      multifaceted and relational ways that dental students experience their
      educational environment. It could point curriculum designers towards strategies
      that assist students develop sophisticated understandings about themselves as
      practitioners, patients and the complexities of dental practice. Suggestions
      about the practical implications of the findings of this research are given.

PMID- 29460403
TI  - Effects of ivabradine on endothelial function, aortic properties and ventricular
      arterial coupling in chronic systolic heart failure patients.
AB  - AIM: Heart rate (HR) is an important prognostic factor in patients affected by
      chronic heart failure (CHF); ivabradine has been demonstrated to significantly
      reduce nonfatal myocardial infarction and hospitalization rate for acute heart
      failure and to improve left ventricular (LV) reverse remodeling, quality of life,
      exercise capacity, and arterial elastance (Ea) in these patients. We aimed at
      evaluating the short-term effects of ivabradine on ventricular-arterial coupling
      (VAC), aortic stiffness, and endothelial function in stable patients with CHF.
      METHODS: We evaluated 30 consecutive CHF patients (LVEF<= 35%, NYHA class II)
      with sinus rhythm and HR >= 70 bpm on optimized pharmacological therapy. All of
      them underwent both transthoracic echocardiogram to assess aortic elastic
      properties (aortic distensibility, AD; aortic stiffness index, ASI; systolic
      aortic strain, SAS) and VAC, and peripheral arterial tonometry to measure
      endothelial function. Therapy with ivabradine 5 mg bid was added and each patient
      was evaluated with the same examinations after 4 months. RESULTS: At the
      baseline, 73% of patients had impaired VAC and 63% endothelial dysfunction. After
      4 months, there was a significant improvement in the VAC value (DeltaVAC -0.10 +/
      0.18, P = .021), mainly linked to Ea (DeltaEa -0.40 +/- 0.23 mm Hg/mL; P =
      .003). All the parameters of aortic elasticity underwent significant improvement
      (DeltaAD 1.82 +/- 1.43 cm2 * dyn- 1, P = .004; DeltaASI -4.73 +/- 6.07, P = .033;
      DeltaSAS -7.98 +/- 4.37%, P = .003). Lastly, we also noted a significant
      improvement of endothelial function (Delta RHI 0.35 +/- 0.35; P < .001). At
      follow-up 40% of patients had impaired VAC (P = .018) and 33% endothelial
      dysfunction (P = .038). CONCLUSION: In patients with CHF adding ivabradine on top
      to the standard optimized medical therapy, when indicated, seems to improve
      endothelial function, aortic properties, and VAC.

PMID- 29460404
TI  - The five key "ingredients" for improving outcomes in cardiogenic shock
      complicating acute myocardial infarction.
AB  - Cardiogenic shock in the setting of acute myocardial infarction (AMICS) carries
      high mortality. A systematic, protocol-driven, approach to AMICS may improve
      outcomes. The 5 key "ingredients" for the managements of AMICS are: (a) early
      diagnosis; (b) hemodynamic assessment; (c) culprit-only coronary
      revascularization; (d) judicious use of mechanic circulatory support; (e) expert
      in-hospital treatment.

PMID- 29460405
TI  - Is optical coherence tomography a coherent strategy for carotid artery stenting?
AB  - Optical coherence tomography (OCT) is rarely necessary to guide clinical
      decisions about the appropriateness of carotid revascularization. For carotid
      artery stenting (CAS), computed tomography angiography is the best imaging tool
      to assess arch, carotid, and lesion-specific anatomy, including vessel dimensions
      and calcification. OCT is a coherent strategy after CAS to assess ambiguous
      angiographic findings and to guide appropriate therapy for dissection,
      thrombosis, and plaque prolapse.

PMID- 29460406
TI  - All stent strut malappositions are not created equal.
AB  - The current meta-analysis evaluates the relationship of late incomplete stent
      apposition (LISA) observed either by IVUS or OCT 6-18 months after PCI and long
      term outcomes, particularly in regard to stent thrombosis (ST) and has
      demonstrated a small but significant increase in ST with LISA. The results of the
      current study do not apply to acute stent malapposition whose relevance to
      adverse outcomes is uncertain based on current evidence and a malapposition
      classification based on presence, length, and severity of malapposed struts. A
      classification of stent malapposition based on cause of malapposition is proposed
      as a method to determine prognostic importance of acute incomplete stent
      apposition.

PMID- 29460407
TI  - Clip versus suture toe to toe: Perspectives on and beyond the evidence base.
AB  - The evidence that StarClose is associated with a higher complication rate than
      Perclose is reasonable if less than robust. Closure results are affected by
      access technique. The rationale for using closure devices in small hole puncture
      is questionable both from a clinical as well as financial standpoint.

PMID- 29460408
TI  - KISS for in-stent restenosis.
AB  - We treat ISR primarily with new DES implantation. DES therapy appears to provide
      the best protection from TVR and possibly death, as well. Be mindful of occult or
      other evidence of incomplete stent expansion of the original stent.

PMID- 29460409
TI  - PPVI in children under 20 kilograms: A quid pro quo?
AB  - Percutaneous PV implantation can be achieved in very small children (<20 kg) The
      clinic impact appears beneficial in the early term Studies to determine whether
      this treatment pathway will preserve RV function and translate to better survival
      needs investigation.

PMID- 29460411
TI  - Associations of sleep quality with incident atrial fibrillation: a meta-analysis.
AB  - BACKGROUND: The strong relationship between sleep apnoea and atrial fibrillation
      (AF) is well known. However, it remains unclear whether the sleep quality is
      related with AF. AIM: To evaluate the associations of sleep duration, insomnia
      and frequent awakening with AF. METHODS: A systematic review was conducted in
      MEDLINE, EMBASE, Cochrane databases from inception through September 2017 to
      identify studies that evaluate the risk of AF in adults with short sleep
      duration, long sleep duration, insomnia and/or frequent awakening. Effect
      estimates from the individual study were extracted and combined using random
      effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Ten
      observational studies (14 296 314 patients) were enrolled. The pooled odds ratios
      (ORs) of AF in individuals with short sleep (<6 h) and long sleep (>8 h) were
      1.20 (95% confidence interval (CI) 0.93-1.55, I2 = 66%) and 1.24 (95% CI 0.96
      1.62, I2 = 58%), respectively. There was no association between increase in sleep
      duration and AF, with a pooled OR of 0.97 (95% CI 0.84-1.12, I2 = 0%). However,
      there were significant associations of AF with insomnia and frequent awakening,
      with pooled ORs of 1.30 (95% CI 1.26-1.35, I2 = 3%) and 1.36 (95% CI 1.13-1.63,
      I2 = 55%), respectively. CONCLUSIONS: Our findings suggest an absence in
      association between AF and sleep duration but reveal the potential association
      between AF and both insomnia and frequent nocturnal awakening. As such, the
      further studies on association of AF and sleep qualities are warranted.

PMID- 29460410
TI  - Lessons learned from the 1-hour post-load glucose level during OGTT: Current
      screening recommendations for dysglycaemia should be revised.
AB  - This perspective covers a novel area of research describing the inadequacies of
      current approaches for diagnosing dysglycaemia and proposes that the 1-hour post
      load glucose level during the 75-g oral glucose tolerance test may serve as a
      novel biomarker to detect dysglycaemia earlier than currently recommended
      screening criteria for glucose disorders. Considerable evidence suggests that a 1
      hour post-load plasma glucose value >=155 mg/dl (8.6 mmol/L) may identify
      individuals with reduced beta-cell function prior to progressing to prediabetes
      and diabetes and is highly predictive of those likely to progress to diabetes
      more than the HbA1c or 2-hour post-load glucose values. An elevated 1-hour post
      load glucose level was a better predictor of type 2 diabetes than isolated 2-hour
      post-load levels in Indian, Japanese, and Israeli and Nordic populations.
      Furthermore, epidemiological studies have shown that a 1-hour PG >=155 mg/dl (8.6
      mmol/L) predicted progression to diabetes as well as increased risk for
      microvascular disease and mortality when the 2-hour level was <140 mg/dl (7.8
      mmol/L). The risk of myocardial infarction or fatal ischemic heart disease was
      also greater among subjects with elevated 1-hour glucose levels as were risks of
      retinopathy and peripheral vascular complications in a Swedish cohort. The
      authors believe that the considerable evidence base supports redefining current
      screening and diagnostic recommendations with the 1-hour post-load level.
      Measurement of the 1-hour PG level would increase the likelihood of identifying a
      larger, high-risk group with the additional practical advantage of potentially
      replacing the conventional 2-hour oral glucose tolerance test making it more
      acceptable in a clinical setting.

PMID- 29460413
TI  - Bayesian statistical models to estimate EQ-5D utility scores from EORTC QLQ data
      in myeloma.
AB  - It is well documented that the modelling of health-related quality of life data
      is difficult as the distribution of such data is often strongly right/left skewed
      and it includes a significant percentage of observations at one. The objective of
      this study is to develop a series of two-part models (TPMs) that deal with these
      issues. Data from the UK Medical Research Council Myeloma IX trial were used to
      examine the relationship between the European Organization for Research and
      Treatment of Cancer (EORTC) QLQ-C30/QLQ-MY20 scores and the European QoL-5
      Dimensions (EQ-5D) utility score. Four different TPMs were developed. The models
      fitted included TPM with normal regression, TPM with normal regression with
      variance a function of participant characteristics, TPM with log-transformed
      data, and TPM with gamma regression and a log link. The cohort of 1839 patients
      was divided into 75% derivation sample, to fit the different models, and 25%
      validation sample to assess the predictive ability of these models by comparing
      predicted and observed mean EQ-5D scores in the validation set, unadjusted R2 ,
      and root mean square error. Predictive performance in the derivation dataset
      depended on the criterion used, with R2 /adjusted-R2 favouring the TPM with
      normal regression and mean predicted error favouring the TPM with gamma
      regression. The TPM with gamma regression performs best within the validation
      dataset under all criteria. TPM regression models provide flexible approaches to
      estimate mean EQ-5D utility weights from the EORTC QLQ-C30/QLQ-MY20 for use in
      economic evaluation.

PMID- 29460412
TI  - The relationship between haemoglobin level and type 1 diabetic nephropathy in Han
      patients in Anhui, China.
AB  - BACKGROUND/AIM: Recent studies have shown that low haemoglobin (Hb) levels
      promote the progression of chronic kidney disease. This study assessed the
      relationship between Hb level and type 1 diabetic nephropathy (DN) in Han
      patients in Anhui, China. METHODS: There was a total of 236 patients diagnosed
      with type 1 diabetes mellitus (T1DM) seen between January 2014 and December 2016
      in our centre. Haemoglobin levels in patients with DN were compared with those
      without DN. The relationship between Hb level and the urinary albumin-creatinine
      ratio (ACR) was examined by Spearman's correlational analysis and multiple
      stepwise regression analysis. The binary logistic multivariate regression
      analysis was performed to analyse the correlated factors for type 1 DN, calculate
      the odds ratio (OR) and 95% confidence interval (CI). The predicting value of Hb
      level for DN was evaluated by area under receiver operation characteristic curve
      (AUROC) for discrimination and Hosmer-Lemeshow goodness-of-fit test for
      calibration. RESULTS: The average Hb levels in the DN group (116.1 +/- 20.8 g/L)
      were significantly lower than the non-DN group (131.9 +/- 14.4 g/L), P < 0.001.
      Hb levels were independently correlated with the urinary ACR in multiple stepwise
      regression analysis. The logistic multivariate regression analysis showed that
      the Hb level (OR: 0.936, 95% CI: 0.910-0.963, P < 0.001) was inversely correlated
      with DN in patients with T1DM. In sub-analysis, low Hb level (Hb < 120 g/L in
      female, Hb < 130 g/L in male) was still negatively associated with DN in patients
      with T1DM. The AUROC was 0.721 (95% CI: 0.655-0.787) in assessing the
      discrimination of the Hb level for DN. The value of P was 0.593 in Hosmer
      Lemeshow goodness-of-fit test. CONCLUSIONS: In patients with T1DM, the Hb level
      is inversely correlated with urinary ACR and DN.

PMID- 29460414
TI  - Tissue engineering of human knee meniscus using functionalized and reinforced
      silk-polyvinyl alcohol composite three-dimensional scaffolds: Understanding the
      in vitro and in vivo behavior.
AB  - Tissue engineered constructs with rapid restoration of mechanical and biological
      properties remain a challenge, emphasizing the need to develop novel scaffolds.
      Here, we present a multicomponent composite three-dimensional scaffold structure
      with biomimetic reinforcement and biomolecule functionalization for meniscus
      tissue engineering. The scaffold structure was developed using 3:1 silk fibroin
      (SF) and polyvinyl alcohol (PVA). Autoclaved eggshell membrane (AESM) powder (1
      3%w/v) was used as reinforcement to enhance biomechanical properties. Further to
      improve cell attachment and proliferation, these scaffolds were functionalized
      using an optimized unique combination of biomolecules. Comprehensive analysis of
      scaffolds was carried out on morphological, structural, mechanical and biological
      functionalities. Their mechanical properties were compared with different native
      human menisci. The results indicated that, functionalized SF-PVA with 3%AESM has
      shown similar order of magnitude of compressive and dynamic mechanical properties
      as in human meniscus. Moreover, 3% AESM based scaffolds were found to support
      better primary human meniscal cellular proliferation and extracellular matrix
      secretion. Immunohistochemical analysis revealed angiogenesis and
      biocompatibility with minimal inflammatory response for subcutaneously implanted
      scaffolds in New Zealand white rabbits. The developed reinforced and
      functionalized SF-PVA scaffolds can uniquely combine the potential for load
      bearing properties with improved in vitro and in vivo support for meniscus tissue
      regeneration. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:
      1722-1731, 2018.

PMID- 29460416
TI  - Sufficient Utilization of Zirconium Ions to Improve the Structure and Surface
      properties of Nickel-Rich Cathode Materials for Lithium-Ion Batteries.
AB  - We doped Zr4+ ions in the outer layer of Ni0.8 Co0.1 Mn0.1 (OH)2 by
      coprecipitation. The distribution of Zr4+ in the final cathode materials showed a
      gradient distribution because of ion migration during the thermal treatment. The
      doped layer was confirmed by using various analysis methods (energy-dispersive X
      ray spectroscopy, XRD, X-ray photoelectron spectroscopy, and TEM), which implies
      that Zr4+ can not only occupy both the transition metal slabs and Li slabs but
      also form a Li2 ZrO3 layer on the surface as a highly ion-conductive layer. The
      doped Zr4+ in the transition metal slabs can stabilize the crystal structure
      because of the strong Zr-O bond energy, and the doped Zr4+ in the Li slabs can
      act as pillar ions to improve the structural stability and reduce cation mixing.
      The gradient doping can take advantage of the "pillar effect" and restrain the
      "blocking effect" of the pillar ions, which reduces irreversible capacity loss
      and improves the cycling and rate performance of the Ni-rich cathode materials.
      The capacity retention of the modified sample reached 83.2 % after 200 cycles at
      1C (200 mA g-1 ) at 2.8-4.5 V, and the discharge capacity was up to 164.7 mAh g-1
      at 10C. This effective strategy can improve the structure stability of the
      cathode material while reducing the amount of non-electrochemical active dopant
      because of the gradient distribution of the dopant. In addition, the highly ion
      conductive layer of Li2 ZrO3 on the surface can improve the rate performance of
      the cathode.

PMID- 29460415
TI  - Research Directions in the Clinical Implementation of Pharmacogenomics: An
      Overview of US Programs and Projects.
AB  - Response to a drug often differs widely among individual patients. This
      variability is frequently observed not only with respect to effective responses
      but also with adverse drug reactions. Matching patients to the drugs that are
      most likely to be effective and least likely to cause harm is the goal of
      effective therapeutics. Pharmacogenomics (PGx) holds the promise of precision
      medicine through elucidating the genetic determinants responsible for
      pharmacological outcomes and using them to guide drug selection and dosing. Here
      we survey the US landscape of research programs in PGx implementation, review
      current advances and clinical applications of PGx, summarize the obstacles that
      have hindered PGx implementation, and identify the critical knowledge gaps and
      possible studies needed to help to address them.

PMID- 29460417
TI  - Seroprevalence of brucellosis in goats and sheep in Thailand: Results from the
      Thai National Brucellosis Surveillance System from 2013 to 2015.
AB  - In Thailand, brucellosis re-emerged in humans in 2003 and is considered a public
      health risk to goat farmers as the disease is endemic in small ruminants. The
      Thai Department of Livestock Development (DLD) established a nationwide
      surveillance system for brucellosis in goats and sheep in 1997. Using data from
      this surveillance system, we describe the seroprevalence of brucellosis from 2013
      to 2015 in small ruminants and the spatial distribution of the disease throughout
      Thailand. Surveillance data collected included the number of animals and herds
      tested, the province of the animal and herd and the laboratory results.
      Seroprevalence was estimated at both the animal and herd levels. During the 3
      year period, 443,561 goats and sheep were tested for brucellosis by the DLD
      throughout Thailand using the Rose Bengal Plate Test (RBPT) and the enzyme-linked
      immunosorbent assay test for Brucella. Among the 3 years, 2013 had the highest
      proportion of herds that tested positive for brucellosis at 13.80% (95% CI,
      12.52, 15.16). Overall, this study found that brucellosis seroprevalence in small
      ruminants is decreasing throughout Thailand. However, there is variability in the
      spread of the disease with provinces in the eastern and western regions of
      Thailand having higher proportions of animals and herds testing positive. Overall
      provinces in the south had the lowest proportion of animals and herds testing
      positive for brucellosis. Periodic review of surveillance data documents the
      impact of the current brucellosis control programme and supports a targeted
      response in higher prevalence regions when there are limited financial resources
      for control measures.

PMID- 29460418
TI  - Reliability of histologic assessment in patients with eosinophilic oesophagitis.
AB  - BACKGROUND: The validity of the eosinophilic oesophagitis (EoE) histologic
      scoring system (EoEHSS) has been demonstrated, but only preliminary reliability
      data exist. AIM: Formally assess the reliability of the EoEHSS and additional
      histologic features. METHODS: Four expert gastrointestinal pathologists
      independently reviewed slides from adult patients with EoE (N = 45) twice, in
      random order, using standardised training materials and scoring conventions for
      the EoEHSS and additional histologic features agreed upon during a modified
      Delphi process. Intra- and inter-rater reliability for scoring the EoEHSS, a
      visual analogue scale (VAS) of overall histopathologic disease severity, and
      additional histologic features were assessed using intra-class correlation
      coefficients (ICCs). RESULTS: Almost perfect intra-rater reliability was observed
      for the composite EoEHSS scores and the VAS. Inter-rater reliability was also
      almost perfect for the composite EoEHSS scores and substantial for the VAS. Of
      the EoEHSS items, eosinophilic inflammation was associated with the highest ICC
      estimates and consistent with almost perfect intra- and inter-rater reliability.
      With the exception of dyskeratotic epithelial cells and surface epithelial
      alteration, ICC estimates for the remaining EoEHSS items were above the
      benchmarks for substantial intra-rater, and moderate inter-rater reliability.
      Estimation of peak eosinophil count and number of lamina propria eosinophils were
      associated with the highest ICC estimates among the exploratory items.
      CONCLUSION: The composite EoEHSS and most component items are associated with
      substantial reliability when assessed by central pathologists. Future studies
      should assess responsiveness of the score to change after a therapeutic
      intervention to facilitate its use in clinical trials.

PMID- 29460420
TI  - Goat milk: Non-invasive source for mammary epithelial cell isolation and in vitro
      culture.
AB  - Mammary epithelial cells (MECs) used to study mammary gland function in vitro are
      typically isolated from mammary tissue. Breast milk offers an alternative source
      of MECs to replace mammary gland tissue. This study aimed to isolate and culture
      MECs from goat milk. Samples of fresh goat milk were collected from early and
      late-lactating Saanen goats. Samples were subjected to isolation, culture and
      characterization for putative MECs. The cells adhered to the culture dishes 1 day
      after isolation and displayed a monolayer pattern, epithelial-like cobblestone
      morphology, and formed alveoli-like structures that are typical of MECs. We
      identified the epithelial origin of the isolated cell by staining with antibodies
      against cytokeratin 8, 18 and alkaline phosphatase. Moreover, some of the
      isolated cells expressed the stem cell marker stage-specific embryonic antigen-4.
      The transcription of Capra hircus beta-casein (CNS2) gene, a candidate gene for
      analysis of lactational function, was detected in MECs after induced
      differentiation. In addition, green fluorescence protein (GFP)-expressing cells
      could be generated from goat milk-derived MECs. This study demonstrated that goat
      MECs can be easily isolated from milk samples collected from early and late
      lactating goats. Our MECs model could be an effective model for in vitro studies
      of milk synthesis and gene targeting in the goat mammary gland. Isolation of MECs
      from goat milk rather than mammary tissue improves animal welfare and can be used
      as a replacement for the animal in future studies.

PMID- 29460419
TI  - Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with
      a mutation in the PTPRQ gene.
AB  - BACKGROUND: A congenital syndrome of hearing loss and vestibular dysfunction
      affects Doberman Pinschers. Its inheritance pattern is suspected to be autosomal
      recessive and it potentially represents a spontaneous animal model of an
      autosomal recessive syndromic hearing loss. HYPOTHESIS/OBJECTIVES: The objectives
      of this study were to use whole genome sequencing (WGS) to identify deleterious
      genetic variants in candidate genes associated with the syndrome and to study the
      prevalence of candidate variants among a population of unaffected Doberman
      Pinschers. ANIMALS: One affected Doberman Pinscher and 202 unaffected Doberman
      Pinschers. METHODS: WGS of the affected dog with filtering of variants against a
      database of 154 unaffected dogs of diverse breeds was performed. Confirmation of
      candidate variants was achieved by Sanger sequencing followed by genotyping of
      the control population of unaffected Doberman Pinschers. RESULTS: WGS and variant
      filtering identified an alteration in a gene associated with both deafness and
      vestibular disease in humans: protein tyrosine phosphatase, receptor type Q
      (PTPRQ). There was a homozygous A insertion at CFA15: 22 989 894, causing a
      frameshift mutation in exon 39 of the gene. This insertion is predicted to cause
      a protein truncation with a premature stop codon occurring after position 2054 of
      the protein sequence that causes 279 C-terminal amino acids to be eliminated.
      Prevalence of the variant was 1.5% in a cohort of 202 unaffected Doberman
      Pinschers; all unaffected Doberman Pinschers were heterozygous or heterozygous
      for the reference allele. CONCLUSION AND CLINICAL IMPORTANCE: We report the
      identification of a genetic alteration on the PTPRQ gene that is associated with
      congenital hearing and vestibular disorder in a young Doberman Pinscher dog.

PMID- 29460421
TI  - Tattoo-Paper Transfer as a Versatile Platform for All-Printed Organic Edible
      Electronics.
AB  - The use of natural or bioinspired materials to develop edible electronic devices
      is a potentially disruptive technology that can boost point-of-care testing. The
      technology exploits devices that can be safely ingested, along with pills or even
      food, and operated from within the gastrointestinal tract. Ingestible electronics
      can potentially target a significant number of biomedical applications, both as
      therapeutic and diagnostic tool, and this technology may also impact the food
      industry, by providing ingestible or food-compatible electronic tags that can
      "smart" track goods and monitor their quality along the distribution chain.
      Temporary tattoo-paper is hereby proposed as a simple and versatile platform for
      the integration of electronics onto food and pharmaceutical capsules. In
      particular, the fabrication of all-printed organic field-effect transistors on
      untreated commercial tattoo-paper, and their subsequent transfer and operation on
      edible substrates with a complex nonplanar geometry is demonstrated.

PMID- 29460422
TI  - Engineered CRISPR/Cas9 system for multiplex genome engineering of polyploid
      industrial yeast strains.
AB  - The CRISPR/Cas9 system has been widely used for multiplex genome engineering of
      Saccharomyces cerevisiae. However, its application in manipulating industrial
      yeast strains is less successful, probably due to the genome complexity and low
      copy numbers of gRNA expression plasmids. Here we developed an efficient
      CRISPR/Cas9 system for industrial yeast strain engineering by using our
      previously engineered plasmids with increased copy numbers. Four genes in both a
      diploid strain (Ethanol Red, 8 alleles in total) and a triploid strain (ATCC
      4124, 12 alleles in total) were knocked out in a single step with 100%
      efficiency. This system was used to construct xylose-fermenting, lactate
      producing industrial yeast strains, in which ALD6, PHO13, LEU2, and URA3 were
      disrupted in a single step followed by the introduction of a xylose utilization
      pathway and a lactate biosynthetic pathway on auxotrophic marker plasmids. The
      optimized CRISPR/Cas9 system provides a powerful tool for the development of
      industrial yeast based microbial cell factories.

PMID- 29460423
TI  - Excess pneumonia and influenza hospitalizations associated with influenza
      epidemics in Portugal from season 1998/1999 to 2014/2015.
AB  - BACKGROUND: The aim of this study was to estimate excess pneumonia and influenza
      (P&I) hospitalizations during influenza epidemics and measure their correlation
      with influenza vaccine coverage in the 65 and more years old, according to the
      type/subtype of influenza virus. METHODS: The study period comprised week 40/1998
      40/2015. Age-specific weekly P&I hospitalizations (ICD-9: 480-487) as main
      diagnosis were extracted from the National Hospital Discharge database. Age
      specific baseline hospitalization rates were estimated by autoregressive
      integrated moving average (ARIMA) model without time periods with excess
      hospitalizations. Excess hospitalizations were calculated by subtracting expected
      hospitalization rates from the observed during influenza epidemic periods.
      Correlation between excess P&I hospitalizations and influenza vaccine coverage in
      the elderly was measured with Pearson correlation coefficient. RESULTS: The
      average excess P&I hospitalizations/season was 19.4/105 (range 0-46.1/105 ), and
      higher excess was observed in young children with <2 years (79.8/105 ) and >=65
      years (68.3/105 ). In epidemics with A(H3) dominant, the highest excess
      hospitalizations were observed among 65 and over. Seasons which influenza B or
      A(H1)pdm09 dominance the highest excess was observed in children with <2 years.
      High negative correlation was estimated between excess hospitalizations
      associated with A(H3) circulation and vaccine coverage in the elderly (r = -.653;
      95% CI: -0.950 to -0.137). CONCLUSION: Over 80% of the influenza epidemics were
      associated with excess hospitalizations. However, excess P&I hospitalizations
      pattern differed from age group and circulating virus. This ecologic approach
      also identified a reduction in excess P&I associated with A(H3) circulation with
      increasing vaccine coverage in the elderly.

PMID- 29460424
TI  - Reflections on The Global Influenza Surveillance and Response System (GISRS) at
      65 Years: An Expanding Framework for Influenza Detection, Prevention and Control.

PMID- 29460425
TI  - Advances in measuring influenza burden of disease.

PMID- 29460426
TI  - Comparative, multidimensional imaging of patent ductus arteriosus and a proposed
      update to the morphology classification system for dogs.
AB  - BACKGROUND: Accurately assessing the morphology and shape of the patent ductus
      arteriosus (PDA) and obtaining measurements are important to avoid procedural
      complications. OBJECTIVES: To characterize and compare PDA morphology, shape, and
      dimensions with angiography and echocardiography. ANIMALS: 25 client-owned dogs
      with echocardiographically confirmed PDA. METHODS: Prospective case series.
      Imaging consisted of single plane angiography, transthoracic echocardiography
      from the right (TTE-R) and left (TTE-L), and two-dimensional, biplane, and three
      dimensional transesophageal echocardiography (TEE-2D and TEE-3D). Measurements
      included angiographic minimal ductal diameter (MDD), echocardiographic pulmonary
      ostium in a single dimension (TTE-R, TTE-L, and TEE-2D) and in perpendicular
      dimensions (TEE-3D) with similar measurements of the ampulla 3 mm above the MDD
      or pulmonary ostium. The morphology and shape of the PDA were characterized.
      RESULTS: Catheter-based occlusion (N = 20) and surgical ligation (N = 5) were
      performed without complication. Angiographic morphology was classified as type II
      (N = 19), type III (N = 1), and other (N = 1). Angiographic MDD and TEE-2D
      pulmonary ostium measurements were significantly (P = .008) but weakly correlated
      (r = .56); similar relationships were found for ampulla diameter measurements (P
      < .0001; r = .75). In general, TEE-2D did not correlate with other imaging
      modalities measurements. Based on TEE-3D measurements, the majority of pulmonary
      ostium (17/24; 71%) and ampulla (19/24; 79%) were oval. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Measurements using different imaging modalities are not
      interchangeable. TEE-3D provided an en face view of the PDA that cannot be
      replicated with other echocardiographic techniques and demonstrated an oval shape
      in the majority of dogs. We propose an update to the current classification
      system to include additional PDA morphologies.

PMID- 29460427
TI  - Alcohol consumption and risk of hematological malignancies: A meta-analysis of
      prospective studies.
AB  - Current convincing evidence suggests that alcohol intake increases the risk of
      several carcinomas, which might subsequently lead to a recommendation toward
      limiting alcohol consumption. However, there are accumulating data worth meta
      analyzing that show a different effect on the risk of hematological malignancies.
      Eligible cohort studies were sought in PubMed database up to August 31, 2016.
      Separate analyses were performed by subtype of hematological malignancy (non
      Hodgkin lymphoma [NHL] and subtypes, Hodgkin lymphoma [HL], leukemia and
      subtypes), time status (ever, current, former), level of consumption (light,
      moderate, heavy), alcoholic beverage (total alcohol, beer, liquor, wine) and
      gender. Moderate and heavy alcohol consumption were significantly associated with
      reduced risk of NHL (relative risk [RR] = 0.85, 95% confidence interval [CI]:
      0.80-0.90 and RR = 0.73, 95%CI: 0.60-0.89, respectively); a protective trend was
      also shown for light alcohol intake (RR = 0.93, 95%CI: 0.87-1.00). Specifically,
      beer consumption was associated with reduced NHL risk (RR = 0.88, 95%CI: 0.81
      0.95). However, the association regarding other alcoholic beverages seemed null.
      The beneficial effects of alcohol mainly pertained to Diffuse Large B-Cell
      Lymphoma (DLBCL) (RR = 0.83, 95%CI: 0.77-0.89) and Follicular Lymphoma (FL) (RR =
      0.85, 95%CI: 0.78-0.93). There was also no association between alcohol
      consumption and risk of HL or leukemias. In contrast to most solid malignancies,
      alcohol seems to confer a protective effect on NHL risk, especially on DLBCL and
      FL subtypes, with beer being notably beneficial.

PMID- 29460428
TI  - Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai
      Population.
AB  - BACKGROUND: Alcohol use (both quantity and dependence) is moderately heritable,
      and genomewide association studies (GWAS) have identified risk genes in European,
      African, and Asian populations. The most reproducibly identified risk genes
      affect alcohol metabolism. Well-known functional variants at the gene encoding
      alcohol dehydrogenase B and other alcohol dehydrogenases affect risk in European
      and African ancestry populations. Similarly, variants mapped to these same genes
      and a well-known null variant that maps to the gene that encodes aldehyde
      dehydrogenase 2 (ALDH2) also affect risk in various Asian populations. In this
      study, we completed the first GWAS for 3 traits related to alcohol use in a Thai
      population recruited initially for studies of methamphetamine dependence.
      METHODS: All subjects were evaluated with the Thai version of the Semi-Structured
      Assessment for Drug Dependence and Alcoholism (SSADDA). A total of 1,045 subjects
      were available for analysis. Three traits were analyzed: flushing, maximum number
      of alcoholic beverages consumed in any lifetime 24-hour period ("MAXDRINKS"), and
      DSM-IV alcohol dependence criterion count. We also conducted a pleiotropy
      analysis with major depression, the only other psychiatric trait where summary
      statistics from a large-scale Asian-population GWAS are available. RESULTS: All 3
      traits showed genomewide significant association with variants near ALDH2, with
      significance ranging from 2.01 * 10-14 (for flushing; lead single nucleotide
      polymorphism (SNP) PTPN11* rs143894582) to pmeta  = 5.80 * 10-10 (for alcohol
      dependence criterion count; lead SNP rs149212747). These lead SNPs flank rs671
      and span a region of over a megabase, illustrating the need for prior biological
      information in identifying the actual effect SNP, rs671. We also identified
      significant pleiotropy between major depression and flushing. CONCLUSIONS: These
      results are consistent with prior findings in Asian populations and add new
      information regarding alcohol use-depression pleiotropy.

PMID- 29460429
TI  - Treatment outcomes after the introduction of a new seizure management protocol.
AB  - BACKGROUND/AIM: The present study aims to determine qualitative outcomes of
      presentations with acute recurrent seizures or status epilepticus to the
      emergency department of our institution after the introduction of a new seizure
      management protocol. METHODS: We performed a retrospective analysis on two
      cohorts of patients for all presentations to the emergency department of our
      institution. Presentations were reviewed from January to July pre-protocol
      introduction and the same period post-protocol. Patients were included if they
      were treated for acute recurrent seizures or status epilepticus. The protocol
      applied a strict treatment regimen and used levetiracetam, valproate and
      phenobarbitone in place of phenytoin. RESULTS: A total of 77 patients was
      included from the pre-protocol cohort and 72 from the post-protocol group. There
      was a significant reduction in intensive care unit (ICU) admission (seven
      patients in cohort 1 and 0 patients in cohort 2) and adverse drug reactions (18
      patients in cohort 1 and four patients in cohort 2). There was a trend towards
      fewer deaths. CONCLUSION: The introduction of the new seizure management protocol
      assessed in this study has resulted in fewer ICU admissions, adverse drug
      reactions and most importantly fewer patient deaths. This is likely attributable
      to a combination of improved efficacy of the newer antiepileptic agents and a
      clearly defined protocol directed therapy.

PMID- 29460430
TI  - Profiling children's emotion regulation behaviours.
AB  - Callear, Harvey, and Bimler (2016, International Journal of Behavioral
      Development, 41, 456) organized children's emotion regulation behaviours into a
      coherent structure. However, further investigation is needed to identify core
      patterns of these emotion regulation behaviours. To identify clusters and
      prototypal constellations of emotion regulation behaviours, the 85 behavioural
      items comprising the Children's Emotion Regulation Inventory (ChERI) were ranked
      by 151 parents in order of applicability, using an ordinal sorting procedure
      (Method of Successive Sorts). Responses were aggregated in empirical scales, for
      classification of the cases using hierarchical and k-means clustering. The scales
      were based on nine key 'hotspots' of children's emotion regulation behaviours,
      interpreted as Outward Engagement, Inward or Somatic Focus, Disengagement,
      Disruptive, Impulsive/Labile, Social Connectedness/Compliance, Generating
      Closeness/Intimacy, Establishing Order and Generating Disorder. Five summary
      styles of children's emotion regulation emerged and are characterized on those
      scales. These hotspots and styles provide guidance to clinicians, parents,
      teachers, and other invested adults to assess and support children's emotional
      development. Statement of contribution What is already known on this subject?
      Measurements of children's emotion regulation predominantly focus on internal
      processes and/or isolated expressions of emotion regulation behaviours. Research
      detailing anger and anxiety emotion regulation styles exists (e.g., Carthy,
      Horesh, Apter, & Gross, 2010, Journal of Psychopathology and Behavioral
      Assessment, 32, 23; Zalewski, Lengua, Wilson, Trancik, & Bazinet, 2011, Journal
      of Experimental Child Psychology, 110, 141). Callear, Harvey, and Bimler (2016,
      International Journal of Behavioral Development, 41, 456) developed the
      Children's Emotion Regulation Inventory to identify children's observable emotion
      regulation strategies. What does this study add? Research does not investigate
      which clusters of children's emotion regulation behaviours are most commonly
      exhibited and nor does it investigate emotion regulation behavioural styles.
      Examines how children's emotion regulation behaviours co-occur. Identifies nine
      core clusters (groupings) of emotion regulation behaviours most commonly observed
      to be exhibited in children. Identifies five emotion regulation behavioural
      styles (common co-occurring patterns of emotion regulation behaviour clusters) in
      children.

PMID- 29460431
TI  - Estimating dispersal in spatiotemporally variable environments using multievent
      capture-recapture modeling.
AB  - Dispersal is a key process in ecological and evolutionary dynamics.
      Spatiotemporal variation in habitat availability and characteristics has been
      suggested to be one of the main cause involved in dispersal evolution and has a
      strong influence on metapopulation dynamics. In recent decades, the study of
      dispersal has led to the development of capture-recapture (CR) models that allow
      movement between sites to be quantified, while handling imperfect detection. For
      studies involving numerous recapture sites, Lagrange et al. () proposed a
      multievent CR model that allows dispersal to be estimated while omitting site
      identity by distinguishing between individuals that stay and individuals that
      move. More recently, Cayuela et al. () extended this model to allow survival and
      dispersal probabilities to differ for the different types of habitat represented
      by several sites within a study area. Yet in both of these modeling systems, the
      state of sites is assumed to be static over time, which is not a realistic
      assumption in dynamic landscapes. For that purpose, we generalized the multievent
      CR model proposed by Cayuela et al. () to allow the estimation of dispersal,
      survival and recapture probabilities when a site may appear or disappear over
      time (MODEL 1) or when the characteristics of a site fluctuate over space and
      time (MODEL 2). This paper first presents these two new modeling systems, and
      then provides an illustration of their efficacy and usefulness by applying them
      to simulated CR data and data collected on two metapopulations of amphibians.
      MODEL 1 was tested using CR data recorded on a metapopulation of yellow-bellied
      toads (Bombina variegata). In this first empirical case, we examined whether the
      drying-out dynamics of ponds and the past dispersal status of an individual might
      affect dispersal behavior. Our study revealed that the probability of facultative
      dispersal (i.e., from a pond group that remained available/flooded) fluctuated
      between years and was higher in individuals that had previously dispersed. MODEL
      2 was tested using CR data collected on a metapopulation of great crested newts
      (Triturus cristatus). In this second empirical example, we investigated whether
      the density of alpine newts (Ichthyosaura alpestris), a potential competitor,
      might affect the dispersal and survival of the crested newt. Our study revealed
      that the departure rate was lower in ponds with a high density of heterospecifics
      than in ponds with a low density of heterospecifics at both inter-annual and
      intra-annual scales. Moreover, annual survival was slightly higher in ponds with
      a high density of heterospecifics. Overall, our findings indicate that these
      multievent CR models provide a highly flexible means of modeling dispersal in
      dynamic landscapes.

PMID- 29460432
TI  - The applied value of medical history, physical examination, colour-Doppler
      ultrasonography and testis scintigraphy in the differential diagnosis of acute
      scrotum.
AB  - Acute scrotum, especially testicular torsion, is a common surgical emergency. A
      delay in diagnosis or management may lead to permanent testicular ischaemic
      damage. Thus, it is particularly important to differentiate testicular torsion
      from other acute scrotum conditions as soon as possible. Our study has
      retrospectively investigated 358 patients with acute scrotum admitted to our
      hospital from the year 2007 to 2016. We have collected a thorough history and
      clinical data and drew the conclusion by comparing clinical features of different
      acute scrotum cases, medical history, imaging and surgical findings. Therefore,
      we propose an innovative "Testicular Torsion (TT) Green Channel" concept. Through
      the combination of a comprehensive medical history, physical examination and
      auxiliary colour-Doppler ultrasonography, the diagnosis of testicular torsion is
      definite in most circumstances. Testis scintigraphy is a novel and complementary
      diagnostic modality that can reduce the negative exploration rate in ambiguous
      and certain cases. The TT Green Channel is a new concept in the management of
      testicular torsion.

PMID- 29460433
TI  - Construction of bionic tissue engineering cartilage scaffold based on three
      dimensional printing and oriented frozen technology.
AB  - Articular cartilage (AC) has gradient features in both mechanics and histology as
      well as a poor regeneration ability. The repair of AC poses difficulties in both
      research and the clinic. In this paper, a gradient scaffold based on poly(lactic
      co-glycolic acid) (PLGA)-extracellular matrix was proposed. Cartilage scaffolds
      with a three-layer gradient structure were fabricated by PLGA through three
      dimensional printing, and the microstructure orientation and pore fabrication
      were made by decellularized extracellular matrix injection and directional
      freezing. The manufactured scaffold has a mechanical strength close to that of
      real cartilage. A quantitative optimization of the Young's modulus and shear
      modulus was achieved by material mechanics formulas, which achieved a more
      accurate mechanical bionic and a more stable interface performance because of the
      one-time molding process. At the same time, the scaffolds have a bionic and
      gradient microstructure orientation and pore size, and the stratification ratio
      can be quantitatively optimized by design of the freeze box and temperature
      simulation. In general, this paper provides a method to optimize AC scaffolds by
      both mechanics and histology as well as a bionic multimaterial scaffold. This
      paper is of significance for cell culture and clinical transplantation
      experiments. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:
      1664-1676, 2018.

PMID- 29460434
TI  - Effects of a wax organogel and alginate gel complex on holy basil (Ocimum
      sanctum) in vitro ruminal dry matter disappearance and gas production.
AB  - BACKGROUND: The objectives of this study were to: (a) select an ideal organogel
      for the oil phase of a novel gel encapsulation technology, (b) optimize the
      formulation of an organogel and sodium alginate-based gel complex, and (c)
      examine the rumen protective ability of the gel by measuring 48-h in vitro
      ruminal dry matter disappearance and gas production from encapsulated dried and
      ground holy basil leaves. RESULTS: A rice-bran wax and canola oil organogel was
      selected for the oil phase of the gel complex as this combination had a 48-h dry
      matter disappearance of 6%, the lowest of all organogels analyzed. The gel
      complex was formulated by homogenizing the organogel with a sodium alginate
      solution to create a low-viscosity oil-in-water emulsion. Average dry matter
      disappearance of gel-encapsulated holy basil was 19%, compared to 42% for the
      free, unprotected holy basil. However, gel encapsulation of holy basil stimulated
      gas production. Specifically, gas production of encapsulated holy basil was four
      times higher than the treatment with holy basil added on top of the gel prior to
      incubation rather than encapsulated within the gel. CONCLUSION: Although the gel
      itself was highly degradable, it is speculated encapsulation thwarted holy
      basil's antimicrobial activity. (c) 2018 Society of Chemical Industry.

PMID- 29460435
TI  - Topical pimecrolimus for paediatric cutaneous mastocytosis.
AB  - BACKGROUND: Most cases of paediatric cutaneous mastocytosis (CM) occur before the
      age of 2 years, and regression occurs in only 67% of children. Given the absence
      of any specific therapy, CM is usually treated symptomatically. A few
      publications have reported the beneficial effect of calcineurin inhibitors for
      CM. AIM: We sought to evaluate the clinical effectiveness and safety profile of
      topical pimecrolimus cream for the treatment of CM. METHODS: We performed a
      retrospective study of all diagnosed cases of CM treated with topical
      pimecrolimus 1% cream between 2013 and 2015. All patients were evaluated in a
      paediatric dermatology unit of a tertiary medical centre. Epidemiological,
      clinical and treatment data, including effectiveness and safety, were reviewed.
      RESULTS: In total, 18 children (11 male, 7 female; age range 3-42 months) with CM
      were evaluated. Of the 146 treated lesions, 39 (26.7%) disappeared and 98 (67%)
      faded or developed postinflammatory hyperpigmentation. Of the 119 papular
      lesions, 24 (16.4%) showed partial flattening and 56 (47%) became macular. Darier
      sign became negative in 14 (82%) of 17 patients. No topical or systemic
      complications were observed. CONCLUSIONS: Topical therapy with pimecrolimus 1%
      cream should be considered in the treatment of CM.

PMID- 29460436
TI  - Truncating variants of the DLG4 gene are responsible for intellectual disability
      with marfanoid features.
AB  - Marfanoid habitus (MH) combined with intellectual disability (ID) is a
      genetically and clinically heterogeneous group of overlapping disorders. We
      performed exome sequencing in 33 trios and 31 single probands to identify novel
      genes specific to MH-ID. After the search for variants in known disease-causing
      genes and non-disease-causing genes with classical approaches, we searched for
      variants in non-disease-causing genes whose pLI was above 0.9 (ExAC Consortium
      data), in which truncating variants were found in at least 3 unrelated patients.
      Only DLG4 gene met these criteria. Data from the literature and various databases
      also indicated its implication in ID. DLG4 encodes post-synaptic density protein
      95 (PSD-95), a protein expressed in various tissues, including the brain. In
      neurons, PSD-95 is located at the post-synaptic density, and is associated with
      glutamatergic receptor signaling (NMDA and AMPA). PSD-95 probably participates in
      dendritogenesis. Two patients were heterozygous for de novo frameshift variants
      and one patient carried a a consensus splice site variant. Gene expression
      studies supported their pathogenicity through haploinsufficiency and loss-of
      function. Patients exhibited mild-to-moderate ID, similar marfanoid features,
      including a long face, high-arched palate, long and thin fingers, pectus
      excavatum, scoliosis and ophthalmological manifestations (nystagmus or
      strabismus). Our study emphasizes the role of DLG4 as a novel post-synaptic
      associated gene involved in syndromic ID associated with MH.

PMID- 29460437
TI  - Examining changes in procedural justice and their influence on problem-solving
      court outcomes.
AB  - The number of problem-solving courts has grown substantially since the mid-1990s.
      Research consistently indicates that participation in these courts lowers
      recidivism, which is often attributed to defendants' increased perceptions of
      procedural justice in these programs. Yet, prior studies are limited in their
      focus, often examining interactions with the judge in a single court or examining
      defendant perceptions and outcomes at a single time point. In the present study,
      we investigate defendant perceptions of procedural justice with judges and case
      managers across multiple problem-solving courts over time. Findings indicate that
      procedural justice varies across court actors and over time. Procedural justice
      is lower among judges than among case managers; however, changes in perceptions
      of procedural justice with the judge are associated with improved court outcomes.
      We suggest that defendant perceptions are variable and complex but important in
      explaining variations in outcomes.

PMID- 29460438
TI  - Does parental coaching affect children's false reports? Comparing verbal markers
      of deception.
AB  - The present study examined differences in children's true and false narratives as
      a function of parental coaching by comparing the verbal markers associated with
      deception. Children (N = 65, 4-7 years old) played the same game with an adult
      stranger over three consecutive days. Parents coached their children to falsely
      allege that they had played a second game and to generate details for the
      fabricated event. One week after the last play session, children were interviewed
      about their experiences. For children with the least amount of parental coaching,
      true and false reports could be distinguished by multiple verbal markers of
      deception (e.g., cognitive processes, temporal information, self-references). The
      fabricated reports of children who spent more time being coaching by a parent
      resembled their truthful reports. These findings have implications for real-world
      forensic contexts when children have been coached to make false allegations and
      fabricate information at the behest of a parent.

PMID- 29460439
TI  - The MRCI with juvenile detainees: optimizing performance or emphasizing
      ecological validity?
AB  - The Miranda Rights Comprehension Instruments (MRCI) are intended to be
      administered to legally involved youths in a setting free from distractions and
      stressors with the explicit goal of assessing the examinee's best understanding.
      However, marked disparities have been observed between juveniles' MRCI
      performance and their unassisted recall of a representative Miranda warning. We
      hypothesized that youths' very strong MRCI performance might be partially due to
      prompts and clarifications used whenever incomplete or ambiguous answers are
      provided. In this archival study, we systematically re-scored three MRCI
      instruments from 231 legally involved youths to evaluate their original responses
      (i.e., non-queried scoring). This approach is viewed as more ecologically valid
      because actual Miranda warnings are typically provided in a routine manner
      without assistance following each Miranda component. For the large majority of
      legally involved juveniles, only small differences were noted between standard
      and non-queried scoring. However, some dramatic decrements were observed,
      especially on the Comprehension of Miranda Rights-II (CMR-II). More specifically,
      15.7% of CMR-II percentiles dropped precipitously by 60% or more, when using the
      non-queried scores. The results are discussed within the context of optimized
      performances versus ecological validity as applied to Miranda evaluations.

PMID- 29460440
TI  - Effect of continuing care for people with cocaine dependence on criminal justice
      sentences.
AB  - While continuing care for substance use treatment has been associated with
      reduced involvement in the criminal justice system, much of this research lacks
      random assignment to continuing care and so is limited by self-selection bias.
      This study sought to determine the impact of adding telephone-based continuing
      care to intensive outpatient programs on criminal justice outcomes for people
      with cocaine dependence. In three continuing care studies, spanning 1998-2008,
      participants were randomly assigned to an intensive outpatient program or an
      intensive outpatient program plus a telephone-based continuing care intervention.
      Cocaine-dependent participants from these three studies were included in the
      analyses, with outcomes derived from a dataset of jurisdiction-wide criminal
      sentences from a state sentencing agency. Multiple logistic regression was
      employed to examine the odds of a criminal conviction occurring in the 4 years
      after enrollment in a continuing care study. The results showed that, controlling
      for a criminal sentence in the previous year, gender, age, and continuing care
      study, people with cocaine dependence randomized to an intensive outpatient
      program plus a telephone-based continuing care intervention had 54% lower odds (p
      = 0.05, odds ratio = 0.46, 95% CI: 0.20-1.02) of a criminal sentence in the 4
      years after enrollment in the continuing care study, compared with those
      randomized to an intensive outpatient program alone. We can conclude that adding
      telephone monitoring and counseling to intensive outpatient programs is
      associated with fewer criminal convictions over a 4-year follow-up period
      compared with intensive outpatient programs alone.

PMID- 29460441
TI  - The prevalence of false confessions in experimental laboratory simulations: A
      meta-analysis.
AB  - We assessed experimental false confession studies using a meta-analysis to
      evaluate the prevalence of false confessions across methodologies and several
      moderator variables. False confessions were more likely in typing task studies
      than in collaborative or individual cheating studies. In typing studies, speed of
      typing did not affect false confession rates, but placement of the forbidden key
      in locations that rendered errors less plausible lowered the false confession
      rates. False-evidence ploys increased the likelihood of false confessions. We
      explore implications for courts, expert witnesses, scholars, and police
      interrogators.

PMID- 29460443
TI  - Aqueous Hydrogenation of Levulinic Acid to 1,4-Pentanediol over Mo-Modified
      Ru/Activated Carbon Catalyst.
AB  - A highly efficient and green process was developed for direct conversion of
      levulinic acid into 1,4-pentanediol over Mo-modified Ru/activated carbon (AC)
      catalyst in a continuous fixed-bed reactor. The Ru-MoOx /AC catalyst was found to
      be efficient for the aqueous-phase hydrogenation of levulinic acid to 1,4
      pentanediol, whereby a high yield (96.7 mol %) of 1,4-pentanediol was obtained
      under mild reaction conditions (70  degrees C, 4 MPa H2 ).

PMID- 29460442
TI  - Fluorescent nanodiamond-bacteriophage conjugates maintain host specificity.
AB  - Rapid identification of specific bacterial strains within clinical,
      environmental, and food samples can facilitate the prevention and treatment of
      disease. Fluorescent nanodiamonds (FNDs) are being developed as biomarkers in
      biology and medicine, due to their excellent imaging properties, ability to
      accept surface modifications, and lack of toxicity. Bacteriophages, the viruses
      of bacteria, can have exquisite specificity for certain hosts. We propose to
      exploit the properties of FNDs and phages to develop phages conjugated with FNDs
      as long-lived fluorescent diagnostic reagents. In this study, we develop a simple
      procedure to create such fluorescent probes by functionalizing the FNDs and
      phages with streptavidin and biotin, respectively. We find that the FND-phage
      conjugates retain the favorable characteristics of the individual components and
      can discern their proper host within a mixture. This technology may be further
      explored using different phage/bacteria systems, different FND color centers and
      alternate chemical labeling schemes for additional means of bacterial
      identification and new single-cell/virus studies.

PMID- 29460444
TI  - Association of fecal calprotectin concentrations with disease severity, response
      to treatment, and other biomarkers in dogs with chronic inflammatory
      enteropathies.
AB  - BACKGROUND: Calprotectin is a marker of inflammation, but its clinical utility in
      dogs with chronic inflammatory enteropathies (CIE) is unknown. OBJECTIVE:
      Evaluation of fecal calprotectin in dogs with biopsy-confirmed CIE. ANIMALS: 127
      dogs. METHODS: Prospective case-control study. Dogs were assigned a canine
      chronic enteropathy clinical activity index (CCECAI) score, and histologic
      lesions severity was assessed. Fecal calprotectin, fecal S100A12, and serum C
      reactive protein (CRP) were measured. Food- or antibiotic-responsive cases
      (FRE/ARE, n = 13) were distinguished from steroid-/immunosuppressant-responsive
      or -refractory cases (SRE/IRE, n = 20). Clinical response to treatment in SRE/IRE
      dogs was classified as complete remission (CR), partial response (PR), or no
      response (NR). RESULTS: Fecal calprotectin correlated with CCECAI (rho = 0.27, P
      = .0065) and fecal S100A12 (rho = 0.90, P < .0001), some inflammatory criteria,
      and cumulative inflammation scores, but not serum CRP (rho = 0.16, P = .12). Dogs
      with SRE/IRE had higher fecal calprotectin concentrations (median: 2.0 MUg/g)
      than FRE/ARE dogs (median: 1.4 MUg/g), and within the SRE/IRE group, dogs with
      PR/NR had higher fecal calprotectin (median: 37.0 MUg/g) than dogs with CR
      (median: 1.6 MUg/g). However, both differences did not reach statistical
      significance (both P = .10). A fecal calprotectin >=15.2 MUg/g separated both
      groups with 80% sensitivity (95% confidence interval [95%CI]: 28%-100%) and 75%
      specificity (95%CI: 43%-95%). CONCLUSIONS AND CLINICAL IMPORTANCE: Fecal
      calprotectin could be a useful surrogate marker of disease severity in dogs with
      CIE, but larger longitudinal studies are needed to evaluate its utility in
      predicting the response to treatment.

PMID- 29460445
TI  - Microvesicles in hepatic and peripheral vein can predict nonresponse to
      corticosteroid therapy in severe alcoholic hepatitis.
AB  - BACKGROUND: Severe alcoholic hepatitis patients have high mortality and limited
      response to corticosteroids. Microvesicles reflect cellular stress and disease
      conditions. AIMS: To investigate whether microvesicles are associated with
      severity, response to steroid therapy and inflammation in severe alcoholic
      hepatitis. METHODS: Microvesicles originating from different cells were studied
      pre-therapy in 101 patients; (71 responder to corticosteroid therapy and 30
      nonresponders) and 20 healthy controls. Microvesicles and cells were determined
      in peripheral and hepatic vein samples using flow cytometry and correlated with
      outcomes. Inflammatory signalling pathways and functional alterations of immune
      cells after stimulation with microvesicles were also investigated. RESULTS:
      Microvesicles mean levels were higher in nonresponders for T cells (CD3+ CD4+ ;
      10.1 MV/MUL vs 5.4; P = 0.06), macrophages (CD68+ CD11b+ ; 136.5 vs 121.9 MV/MUL;
      P = 0.01), haematopoietic stem-cells (CD45+ CD34+ ; 116.8 vs 13.4 MV/MUL; P =
      0.0001) and hepatocytes (ASGPR+ ; 470 vs 361 MV/MUL; P = 0.01); the latter two
      predicting steroid nonresponse in 94% patients at baseline in peripheral plasma.
      Microvesicle levels correlated with histological and liver disease severity
      indices. Whereas, in non-responders hepatic vein CD34+ cells were lower (P =
      0.02), the CD34+ microvesicles there from were higher (P = 0.04), thus suggesting
      impaired regeneration. Also, microvesicles of 0.2-0.4 MUm size were higher in
      nonresponders (P < 0.03) at baseline. Microvesicles from patients trigger more (P
      = 0.04) ROS generation, TNF-alpha production (P = 0.04) and up-regulate pro
      inflammatory cytokine related genes in neutrophils in vitro. CONCLUSIONS: Pre
      therapy peripheral plasma levels of CD34+ and ASGPR+ microvesicles are reliable
      non-invasive markers of steroid nonresponse and mortality in patients with severe
      alcoholic hepatitis.

PMID- 29460447
TI  - A selection of abstracts presented at the 45th annual conference of the
      Anatomical Society of Southern Africa (ASSA), 23-26 April 2017, Club Mykonos,
      Langebaan, Western Cape, South Africa.

PMID- 29460446
TI  - Effect of sotalol on heart rate, QT interval, and atrial fibrillation cycle
      length in horses with atrial fibrillation.
AB  - BACKGROUND: Based on its pharmacokinetic profile and electrophysiological effects
      in healthy horses, sotalol potentially could be used as a long-term PO
      antiarrhythmic drug in horses. OBJECTIVES: To evaluate the effect of sotalol on
      heart rate (HR), QT interval, atrial fibrillatory rate, and success of
      cardioversion in horses with naturally occurring chronic atrial fibrillation
      (AF). ANIMALS: Twenty-eight horses referred for transvenous electrical
      cardioversion of AF were treated with 2 mg/kg sotalol PO q12h for 3 days before
      cardioversion, and 13 horses underwent the same protocol without sotalol
      administration. METHODS: Retrospective study. Before and after sotalol or no
      treatment, the HR was measured at rest and during an exercise test. The QT
      interval and atrial fibrillation cycle length (AFCL) were measured at rest using
      tissue Doppler velocity imaging. RESULTS: In the control group, no significant
      differences were found between the 2 examinations. In the sotalol group, the HR
      at rest and during exercise was significantly lower after sotalol treatment,
      whereas the QT interval and AFCL measured by tissue Doppler increased
      significantly. Cardioversion to sinus rhythm was achieved in 25/28 horses in the
      sotalol group and all horses in the control group, but the median number of
      shocks and energy at cardioversion were significantly lower in the sotalol group.
      CONCLUSIONS AND CLINICAL IMPORTANCE: In horses with AF, sotalol administration
      results in class III antiarrhythmic effects and beta-blocking activity, with
      moderate HR reduction during exercise.

PMID- 29460448
TI  - T-cell modulation by cyclophosphamide for tumour therapy.
AB  - The power of T cells for cancer treatment has been demonstrated by the success of
      co-inhibitory receptor blockade and adoptive T-cell immunotherapies. These
      treatments are highly successful for certain cancers, but are often personalized,
      expensive and associated with harmful side effects. Other T-cell-modulating drugs
      may provide additional means of improving immune responses to tumours without
      these disadvantages. Conventional chemotherapeutic drugs are traditionally used
      to target cancers directly; however, it is clear that some also have significant
      immune-modulating effects that can be harnessed to target tumours.
      Cyclophosphamide is one such drug; used at lower doses than in mainstream
      chemotherapy, it can perturb immune homeostasis, tipping the balance towards
      generation of anti-tumour T-cell responses and control of cancer growth. This
      review discusses its growing reputation as an immune-modulator whose multiple
      effects synergize with the microbiota to tip the balance towards tumour immunity
      offering widespread benefits as a safe, and relatively inexpensive component of
      cancer immunotherapy.

PMID- 29460449
TI  - Powerful and robust cross-phenotype association test for case-parent trios.
AB  - There has been increasing interest in identifying genes within the human genome
      that influence multiple diverse phenotypes. In the presence of pleiotropy, joint
      testing of these phenotypes is not only biologically meaningful but also
      statistically more powerful than univariate analysis of each separate phenotype
      accounting for multiple testing. Although many cross-phenotype association tests
      exist, the majority of such methods assume samples composed of unrelated subjects
      and therefore are not applicable to family-based designs, including the valuable
      case-parent trio design. In this paper, we describe a robust gene-based
      association test of multiple phenotypes collected in a case-parent trio study.
      Our method is based on the kernel distance covariance (KDC) method, where we
      first construct a similarity matrix for multiple phenotypes and a similarity
      matrix for genetic variants in a gene; we then test the dependency between the
      two similarity matrices. The method is applicable to either common variants or
      rare variants in a gene, and resulting tests from the method are by design robust
      to confounding due to population stratification. We evaluated our method through
      simulation studies and observed that the method is substantially more powerful
      than standard univariate testing of each separate phenotype. We also applied our
      method to phenotypic and genotypic data collected in case-parent trios as part of
      the Genetics of Kidneys in Diabetes (GoKinD) study and identified a genome-wide
      significant gene demonstrating cross-phenotype effects that was not identified
      using standard univariate approaches.

PMID- 29460450
TI  - Evaluation of the new AspID polymerase chain reaction assay for detection of
      Aspergillus species: A pilot study.
AB  - The newly developed AspID PCR assay for detection of Aspergillus spp. was
      evaluated with an interlaboratory quality control programme panel and human
      bronchoalveolar lavage fluid (BALF) samples. With the quality control programme,
      8 out of 9 panel members were correctly identified. With the clinical study, 36
      BALF samples that had been obtained from 18 patients with invasive pulmonary
      aspergillosis (IPA) and 18 without IPA were investigated. Sensitivity,
      specificity, positive and negative likelihood ratio for the AspID assay were
      94.1% (95% CI 73.3-99.9), 76.5% (95% CI 50.1-93.2), 4 (95% CI 1.7-9.5) and 0.1
      (95% CI 0.01-0.5) respectively.

PMID- 29460451
TI  - Muscles and fascial elements of the antebrachium and manus of the African
      elephant (Loxodonta africana, Blumenbach 1797): starring comparative and
      functional considerations.
AB  - The structure of the limbs of elephants is unusual among mammals. In African
      elephants (Loxodonta africana, Blumenbach 1797), the front limbs serve to support
      the greatest part of the body mass of the largest land animal. In this study, we
      present new and detailed anatomical data regarding muscular and specific fascial
      structures of the lower front limb which were examined by means of standard
      anatomical and histological techniques. The muscles and tendons of the forearm
      (antebrachium) and hand (manus) are tightly surrounded by thick, highly elastic
      fascial layers which fuse with the lacertus (lac.) fibrosus and the so-called
      ligamentum (lig.) humeroulnare. A well-developed musculus (m.) brachioradialis
      occupies the proximolateral aspect of the forearm and its tendon inserts together
      with the lac. fibrosus on the os carpi intermedium. The lac. fibrosus, the lig.
      humeroulnare and the m. flexor carpi radialis reveal a large proportion of
      elastic fibres. These three structures may play an important role in storing
      strain energy thus promoting energy-saving locomotion. On the palmar aspect of
      the carpus, metacarpus and digits, short flexor, abductor, adductor, lumbricales
      and interossei muscles are present, whereas supinator muscles are absent in all
      specimens. The short muscles of the hand together with specific dorsal tendons
      enable precise movements of specific toes.

PMID- 29460452
TI  - The effect of digital rectal exam on the 4Kscore for aggressive prostate cancer.
AB  - BACKGROUND: The 4Kscore is a new commercially available blood-based diagnostic
      test which predicts risk for aggressive, clinically significant prostate cancer
      on prostate biopsy. The 4Kscore is currently restricted to patients who have not
      had a digital rectal exam (DRE) in the previous 96 h, owing to prior mixed data
      suggesting that prostate specific antigen (PSA) isoforms may increase by a
      statistically significant-if not necessarily clinically significant-amount
      shortly after DRE. Our primary objective was to determine if 4Kscore test results
      are affected by a preceding DRE. METHODS: Participants at a Prostate Cancer
      Awareness Week screening event sponsored by the Prostate Conditions Education
      Council filled out clinical history questionnaires and had blood samples for
      4Kscore testing drawn prior to DRE, then 15-45 min following DRE. Patients with
      prior cancer diagnosis, 5-alpha reductase inhibitor medication use, or lower
      urinary tract procedures in the prior 6 months were excluded, resulting in a
      population of 162 participants for analysis. Values were then compared to
      determine if there was a significant difference in 4Kscore following DRE.
      RESULTS: A statistically significant increase was seen in levels of 3 kallikreins
      measured (total PSA, free PSA, and intact PSA; median <0.03 ng/mL for all). This
      resulted in a small but statistically significant decrease in post-DRE 4Kscore
      (median absolute score decrease 0.43%). Using a 4Kscore cutoff of 7.5% resulted
      in reclassification of 10 patients (6.2%), nine of whom were "downgraded" from
      above the cutoff to below. CONCLUSIONS: If the blood draw for the 4 K score is
      performed after a screening DRE, there is a statistically significant difference
      in the 4 K score results, but in the vast majority of cases it would not affect
      clinical decision making.

PMID- 29460454
TI  - Management of acute ischaemic stroke in patients with dementia.

PMID- 29460453
TI  - Severe maternal morbidity due to sepsis: The burden and preventability of disease
      in New Zealand.
AB  - BACKGROUND: Sepsis is a life-threatening systemic condition that appears to be
      increasing in the obstetric population. Clinical detection can be difficult and
      may result in increased morbidity via delays in the continuum of patient care.
      AIMS: To describe the burden of severe maternal morbidity (SMM) caused by sepsis
      in New Zealand and investigate the potential preventability. METHODS: A
      multidisciplinary expert review panel was established to review cases of
      obstetric sepsis admitted to intensive care or high-dependency units over an 18
      month span in New Zealand. Cases were then analysed for the characteristics of
      infection and their preventability. RESULTS: Fifty cases met the inclusion
      criteria, most commonly due to uterine, respiratory or kidney infection. Fifty
      per cent (25) of these cases were deemed potentially preventable, predominantly
      due to delays in diagnosis and treatment. CONCLUSIONS: A high index of suspicion,
      development of early recognition systems and multi-disciplinary training are
      recommended to decrease preventable cases of maternal sepsis.

PMID- 29460455
TI  - Brain Quantitative MRI Metrics in Astronauts as a Unique Professional Group.
AB  - BACKGROUND AND PURPOSE: As part of its technological sophistication, the
      International Space Station (ISS) Program operates a robust medical surveillance
      schedule for its rotating 6-person crew to control the known health risks and to
      address knowledge gaps related to human health in space flight environment.
      Recent evidence on visual impairment in a subset of ISS crew has renewed the
      interest in the effects of long-duration space flight on the central nervous
      system (CNS). Through retrospective analysis in a sample of 10 healthy
      astronauts, we demonstrate the utility of multimodal quantitative magnetic
      resonance imaging (qMRI) with diffusion tensor imaging (DTI)-based customized
      brain templates to examine the structural attributes of various CNS compartments
      in this occupational group. METHODS: The study included 10 healthy astronauts (45
      55 years). All subjects had previous space flights with the median duration of
      110 days. Multimodal quantitative structural imaging modalities performed and
      used in analyses. RESULTS: A host of CNS features are presented, which are
      largely commensurate with the available normative data. Remarkably, some of our
      findings demonstrate statistically significant positive features suggestive of
      structural neuroplasticity conceivably associated with the professional
      activities of astronauts, and compensatory neurogenesis that counterweighs the
      expected normative volume loss with age. CONCLUSIONS: The novelty of this
      exploratory report is in the demonstration of a qMRI toolset as a potential
      capability for characterization and surveillance of unique professional groups,
      and for future prospective examinations of the effects of various long-term
      exposures on CNS.

PMID- 29460456
TI  - Acute haemolysis, DIC and renal failure after transfusion of uncross-matched
      blood during trauma resuscitation: illustrative case and literature review.
AB  - AIMS/OBJECTIVES: The aims of this study were to report a patient with acute
      haemolytic transfusion reaction (HTR) after transfusing uncross-matched red blood
      cell (RBC) units and to identify the frequency of this complication. BACKGROUND:
      Uncross-matched RBC units are commonly transfused in emergencies, but the
      frequency of acute HTR is unknown. METHODS: We describe a male stabbing victim
      who received three units of uncross-matched RBC units complicated by acute
      intravascular HTR, disseminated intravascular coagulation (DIC) and renal
      failure. We identified 14 studies evaluating the frequency of acute HTR post
      emergency transfusion of uncross-matched RBC units. RESULTS: Acute HTR was shown
      by haemoglobinuria, free-plasma haemoglobin and methemalbumin, with anti-K and
      anti-Fya eluted from recipient red cells; acute DIC featured severe
      hypofibrinogenemia, thrombocytopenia, elevated fibrin D-dimer and multiple
      bilateral renal infarcts. Two of the three transfused units reacted with pre
      existing RBC alloantibodies [anti-K (titre, 128), anti-Fya (titre, 512)],
      explained by transfusion 25 years earlier. Our literature review found the
      frequency of acute HTR following emergency transfusion of uncross-matched RBC
      units to be 2/3998 [0.06% (95% CI, 0.01-0.21%)]. CONCLUSIONS: Although emergency
      transfusion of uncross-matched blood is commonly practiced at trauma centres
      worldwide, with low risk of acute HTR (<1/1000), our well-documented patient case
      demonstrates the potential for acute HTR with severe complications.

PMID- 29460457
TI  - Aberrant migration and surgical removal of a heartworm (Dirofilaria immitis) from
      the femoral artery of a cat.
AB  - A cat was evaluated for an acute-onset of right pelvic limb paresis. Thoracic
      radiographs revealed normal cardiac size and tortuous pulmonary arteries.
      Abdominal ultrasound identified a heartworm (HW) extending from the caudal
      abdominal aorta into the right external iliac artery and right femoral artery.
      The cat was HW-antigen positive. Echocardiography revealed a HW within the right
      branch of the main pulmonary artery and evidence of pulmonary hypertension. An
      agitated-saline contrast echocardiogram revealed a small right to left
      intracardiac shunt at the level of the atria. Surgical removal of the HW was
      performed with no substantial postoperative complications. There was return of
      blood flow and improved motor function to the limb. The cat remains mildly
      paretic on the affected limb with no other clinical signs.

PMID- 29460458
TI  - Thyroid function in asphyxiated newborns who received hypothermia therapy.
AB  - BACKGROUND: Thyroid function in asphyxiated newborns who received hypothermia
      therapy and its relation to neurological outcome are not well described. METHODS:
      We performed a prospective study to measure thyroid function in 12 asphyxiated
      newborns who received hypothermia therapy. We measured serum thyroid-stimulating
      hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) on
      admission, at 24, 72, and 96 h after birth, and at discharge (range, 17-54 days).
      The 12 newborns were divided into two groups based on the presence of brain
      injury on head magnetic resonance imaging (six in the abnormal imaging group and
      six in the normal imaging group), and thyroid function was compared between the
      two groups. RESULTS: Serum TSH was within the normal range in the 12 newborns.
      Serum FT3 and FT4 remained low at 24, 72, and 96 h after birth, and returned to
      normal range at discharge in the 12 newborns. There was no significant difference
      in serum TSH between the two groups, but serum FT3 at 96 h after birth, and serum
      FT4 at 72 and 96 h after birth, were significantly lower in the abnormal imaging
      group than in the normal imaging group (P = 0.02; P = 0.03; and P = 0.01,
      respectively). CONCLUSIONS: Asphyxiated newborns have transient low thyroid
      hormone levels at 24-96 h after birth. Serum FT3 and FT4 between 72 and 96 h
      after birth may predict brain injury in asphyxiated newborns.

PMID- 29460459
TI  - Prevalence of neuropathic pain and sensory alterations after dental implant
      placement in a university-based oral surgery department: A retrospective cohort
      study.
AB  - OBJECTIVE: To determine the prevalence and the clinical features of patients with
      neuropathic pain and sensory alterations after dental implant placement.
      BACKGROUND: Literature is very scarce concerning the prevalence of neuropathic
      pain after dental implant placement. PATIENTS AND METHODS: A retrospective cohort
      study was made in patients submitted to dental implant placement in the Dental
      Hospital of the University of Barcelona. A descriptive analysis of the data was
      made, and the 95% confidence intervals (95% CI) were calculated for the
      prevalences. RESULTS: The study sample was composed of 1156 subjects of whom,
      1012 patients (3743 dental implants) met the study inclusion criteria. Four
      hundred and seventeen patients (41.2%) were male and 595 (58.8%) were female,
      with a mean age of 60.7 years (range 16-90 years). Three patients were diagnosed
      as having painful post-traumatic trigeminal neuropathy (PPTN), which corresponds
      to a prevalence of 0.3% (95% CI: 0%-0.6%). Additionally, 5 patients (0.5%; 95%
      CI: 0%-1.07%) presented trigeminal neuropathy without pain (TNWP). The combined
      prevalence of both disorders was 0.8% (95% CI: 0.02%-1.3%). All patients with
      PPTN and TNWP were 60 years old or older, with a total combined prevalence of
      1.48% (95% CI: 0.46%-2.5%) in this age group. Additionally, the prevalence in
      this age group for women was 1.85% (95%CI: 0.38%-3.31%). CONCLUSIONS: Neuropathic
      pain after dental implant placement is very infrequent (0.3%) in a University
      Oral Surgery department. However, the presence of trigeminal neuropathies can be
      slightly higher and can affect up to 0.5% of patients. Older female patients seem
      to be more prone to this rare and disabling complication.

PMID- 29460460
TI  - Phosphoric Acid Catalyzed Asymmetric [2+2] Cyclization/Penicillin-Penillonic Acid
      Rearrangement.
AB  - Enantioselective synthesis of imidazolidin-5-ones through a phosphoric acid
      catalyzed reaction between azlactones and N-substituted beta-carbolines is
      reported. The reaction takes place via an initial formal [2+2] cycloaddition to
      generate an alpha-amino-beta-lactam, which subsequently undergoes an acid
      catalyzed asymmetric penicillin-penillonic acid (PPA) rearrangement with high
      diastereo- and enantioselectivity. To the best of our knowledge, this represents
      the first [2+2] cyclization of azlactones with imines and the first asymmetric
      PPA rearrangement, which are linked together by the phosphoric acid catalyst.

PMID- 29460462
TI  - Cri du Chat syndrome: Characteristics of 73 Brazilian patients.
AB  - BACKGROUND: Cri du Chat syndrome (CdCS) is a genetic syndrome caused by deletions
      in the short arm of chromosome 5. Although the main clinical features of CdCS are
      well known, the neurocognitive and behavioural characteristics of the phenotype
      are rarely described in detail in the literature. In this study, we analysed the
      main phenotypic features of CdCS from a parental perspective. METHOD: A
      questionnaire was sent to 700 Brazilian families that were registered in the
      Brazilian Association of CdCS. The questions involved specific domains of CdCS,
      such as pregnancy and birth conditions, recurrence of the disease in the family,
      current major health problems, and aspects of cognitive development. RESULTS: In
      total, 73 questionnaires were completed: 44 females and 29 males, ranging from
      9.5 months old to 40 years old (mean = 13.8 years; median = 12 years). Most of
      the parents noticed the typical cat-like cry at birth (94.4%). The age at
      diagnosis of CdCS ranged from the time of birth to 180 months (mean = 14 months;
      median = 6 months), while one case was diagnosed during pregnancy. In all of the
      cases, the diagnosis of CdCS was made by G-banding karyotype analysis. In 66.2%
      of the cases, the parents underwent cytogenetic investigation. A total of 52.1%
      of the parents answered that they did not remember what the recurrence risk of
      CdCS was in their family. The main health problems that were reported were as
      follows: swallowing problems (80.3%), feeding problems (80.3%), congenital heart
      disease (31.5%), spine abnormalities (28.8%), and neurological symptoms (20.5%),
      including seizures (11%). The behavioural problems that were reported were as
      follows: aggressive behaviour, stereotypies, anxiety, phobias, and genital
      manipulation/masturbation. Neurodevelopmental delay was reported in all of the
      cases. Independent walking was achieved in 72.2% of the patients. Approximately
      50% of the patients never presented expressive language, and most of the patients
      are dependent on others for their daily activities. CONCLUSIONS: The
      questionnaire was a pioneer initiative in the CdCS support group, and the answers
      used in this study can improve the health care assistance to these patients
      because they focus attention on the demands from a parental perspective. In
      addition, nearly half of the families stated that they did not remember
      information regarding recurrence risk, which reinforces the importance of genetic
      counselling follow-up and the need for the expansion of genetic services in
      Brazil.

PMID- 29460461
TI  - Expressive suppression is associated with state paranoia in psychosis: An
      experience sampling study on the association between adaptive and maladaptive
      emotion regulation strategies and paranoia.
AB  - OBJECTIVES: Although emotional instability and problems in emotion regulation
      (ER) are known to be linked to the formation and maintenance of psychosis and
      paranoia, it remains unclear whether the use of specific ER strategies is
      associated with it. The first aim of the study was to explore the association
      between emotional instability and paranoia. The second and third aims were to
      investigate whether the use of maladaptive ER strategies leads to paranoia in
      patients with psychosis in daily life and whether the use of more adaptive ER
      strategies reduces paranoia. DESIGN: A prospective momentary assessment study
      over the course of 6 days was performed. METHOD: Participants with psychosis (n =
      32) reported repeatedly over six consecutive days on the presence and instability
      of positive and negative emotions, their use of adaptive (reappraisal,
      acceptance, distraction, social sharing, reflection) and maladaptive ER
      strategies (rumination, expressive suppression) and momentary paranoia in their
      daily life. RESULTS: Hierarchical linear regression analysis revealed that
      patients with psychosis who presented pronounced instability of negative emotions
      showed more severe levels of state paranoia. In addition, patients with psychosis
      who used expressive suppression when confronted with negative emotions at one
      point in time presented more pronounced levels of state paranoia at the following
      point in time. CONCLUSION: The results presented here suggest that both emotional
      instability and the use of expressive suppression might cause state paranoia and
      thus add to our understanding of causal mechanisms related to paranoia such as
      instability of negative emotions and the use of less adaptive ER strategies.
      PRACTITIONER POINTS: Maladaptive emotion regulation strategies and more
      pronounced instability of negative emotions are relevant to paranoia in patients
      with psychosis and should be a special focus of CBTp interventions. Future
      interventions designed for patients suffering from paranoia should promote coping
      with unstable negative emotions and replacing or reducing maladaptive emotion
      regulation strategies with adaptive ones.

PMID- 29460463
TI  - Association of peak atrial longitudinal strain with atrial fibrillation
      recurrence in patients with chronic lung diseases following radiofrequency
      ablation.
AB  - BACKGROUND: Strain was shown associated with atrial fibrillation (AF) recurrence
      after radiofrequency ablation (RFA), but data on AF patients complicated with
      chronic lung diseases (CLD) were rare. AIM: This study was designed to evaluate
      the relationship of baseline atrial function with AF recurrence in these patients
      using speckle-tracking echocardiography. METHODS: Average strain values (median:
      2 days before RFA) were calculated for 87 AF patients (Mean age: 61.91 years,
      male: 71.26%) with CLD undergoing RFA from 2013 to 2014. Of these patients, 25
      (28.74%) experienced AF recurrence during a mean follow up of 10.3 months.
      RESULTS: Peak right atrial longitudinal strain (R-PALS) was associated with peak
      left atrial longitudinal strain (L-PALS, Standardised beta = 0.45, P < 0.001) in
      multivariate linear regression. Multivariate Cox regression analysis showed R
      PALS was associated with AF recurrence (hazard ratio, 0.86; 95% confidence
      interval (CI), 0.78-0.96, P = 0.005) in CLD. Patients with R-PALS >=14.69% had
      higher AF free rate compared with R-PALS<14.69% using Kaplan-Meier analysis (log
      rank, P < 0.001). R-PALS had similar C-index compared to L-PALS (difference:
      0.03, 95%CI: -0.06-0.12, P = 0.53) and combined R-PALS and L-PALS (difference:
      0.005, 95%CI: -0.04-0.05, P = 0.84) associated with AF recurrence in CLD.
      CONCLUSION: R-PALS, L-PALS and combined R-PALS and L-PALS are important factors
      associated with AF recurrence following RFA in patients with CLD.

PMID- 29460464
TI  - Effect of sucralfate on gastric permeability in an ex vivo model of stress
      related mucosal disease in dogs.
AB  - BACKGROUND: Sucralfate is a gastroprotectant with no known systemic effects. The
      efficacy of sucralfate for prevention and treatment of stress-related mucosal
      diseases (SRMD) in dogs is unknown. HYPOTHESIS/OBJECTIVES: To develop a canine ex
      vivo model of SRMD and to determine the effect of sucralfate on mucosal barrier
      function in this model. ANIMALS: Gastric antral mucosa was collected immediately
      postmortem from 29 random-source apparently healthy dogs euthanized at a local
      animal control facility. METHODS: Randomized experimental trial. Sucralfate (100
      mg/mL) was applied to ex vivo canine gastric mucosa concurrent with and after
      acid injury. Barrier function was assessed by measurement of transepithelial
      electrical resistance (TER) and radiolabeled mannitol flux. RESULTS: Application
      of acidified Ringers solution to the mucosal side of gastric antrum caused a
      reduction in gastric barrier function, and washout of acidified Ringers solution
      allowed recovery of barrier function (TER: 34.0 +/- 2.8% of control at maximum
      injury, 71.3 +/- 5.5% at recovery, P < .001). Sucralfate application at the time
      of injury or after injury significantly hastened recovery of barrier function
      (TER: 118.0 +/- 15.2% of control at maximum injury, P < .001 and 111.0 +/- 15.5%
      at recovery, P = .35). CONCLUSIONS AND CLINICAL IMPORTANCE: Sucralfate appeared
      effective at restoring defects in gastric barrier function induced by acid and
      accelerating repair of tissues subjected to acid in this model, suggesting that
      sucralfate could have utility for the treatment and prevention of SRMD in dogs.

PMID- 29460465
TI  - A study on the effect of detector resolution on gamma index passing rate for VMAT
      and IMRT QA.
AB  - The main objectives of this study are to (1) analyze the sensitivity of various
      gamma index passing rates using different types of detectors having different
      resolutions and (2) investigate the sensitivity of various gamma criteria in
      intensity-modulated radiation therapy (IMRT) and volumetrically modulated arc
      therapy (VMAT) quality assurance (QA) for the detection of systematic multileaf
      collimator (MLC) errors using an electronic portal imaging device (EPID) and
      planar (MapCheck2) and cylindrical (ArcCheck) diode arrays. We also evaluated
      whether the correlation between the gamma passing rate (%GP) and the percentage
      dose error (%DE) of the dose-volume histogram (DVH) metrics was affected by the
      finite spatial resolution of the array detectors. We deliberately simulated
      systematic MLC errors of 0.25 mm, 0.50 mm, 0.75 mm, and 1 mm in five clinical
      nasopharyngeal carcinoma cases, thus creating 40 plans with systematic MLC
      errors. All measurements were analyzed field by field using gamma criteria of
      3%/3 mm, 3%/2 mm, 3%/1 mm, and 2%/2 mm, with a passing rate of 90% applied as the
      action level. Our results showed that 3%/1 mm is the most sensitive criterion for
      the detection of systematic MLC errors when using EPID, with the steepest slope
      from the best-fit line and an area under the receiver operating characteristic
      (ROC) curve >0.95. With respect to the 3%/1 mm criterion, a strong correlation
      between %GP and %DE of the DVH metrics was observed only when using the EPID.
      However, with respect to the same criteria, a 0.75 mm systematic MLC error can go
      undetected when using MapCheck2 and ArcCheck, with an area under the ROC curve
      <0.75. Furthermore, a lack of correlation between %GP and %DE of the DVH metrics
      was observed in MapCheck2 and ArcCheck. In conclusion, low-spatial resolution
      detectors can affect the results of a per-field gamma analysis and render the
      analysis unable to accurately separate erroneous and non-erroneous plans. Meeting
      these new sensitive criteria is expected to ensure clinically acceptable dose
      errors.

PMID- 29460466
TI  - The role of NFkappaB in the three stages of pregnancy - implantation,
      maintenance, and labour: a review article.
AB  - : The transcription factor nuclear factor kappa B (NFkappaB) controls the
      expression of over 400 genes, some of which are associated with reproductive
      events. During implantation, immune cells accumulate in the maternal-fetal
      interface; they secrete inflammatory mediators under the control of NFKB, the
      level of which also rises. NFKB is then downregulated to maintain gestation, but
      its level rises again before birth to manage prostaglandin, cytokine, and
      chemokine synthesis, and to stimulate uterine contraction. This review summarises
      the current state of knowledge about NFkappaB and its role in the molecular
      regulation of processes related to pregnancy development. TWEETABLE ABSTRACT:
      This review examines the current state of knowledge about role of NFkappaB in the
      development of pregnancy.

PMID- 29460467
TI  - Variability of sun-induced chlorophyll fluorescence according to stand age
      related processes in a managed loblolly pine forest.
AB  - Leaf fluorescence can be used to track plant development and stress, and is
      considered the most direct measurement of photosynthetic activity available from
      remote sensing techniques. Red and far-red sun-induced chlorophyll fluorescence
      (SIF) maps were generated from high spatial resolution images collected with the
      HyPlant airborne spectrometer over even-aged loblolly pine plantations in North
      Carolina (United States). Canopy fluorescence yield (i.e., the fluorescence flux
      normalized by the light absorbed) in the red and far-red peaks was computed. This
      quantifies the fluorescence emission efficiencies that are more directly linked
      to canopy function compared to SIF radiances. Fluorescence fluxes and yields were
      investigated in relation to tree age to infer new insights on the potential of
      those measurements in better describing ecosystem processes. The results showed
      that red fluorescence yield varies with stand age. Young stands exhibited a
      nearly twofold higher red fluorescence yield than mature forest plantations,
      while the far-red fluorescence yield remained constant. We interpreted this
      finding in a context of photosynthetic stomatal limitation in aging loblolly pine
      stands. Current and future satellite missions provide global datasets of SIF at
      coarse spatial resolution, resulting in intrapixel mixture effects, which could
      be a confounding factor for fluorescence signal interpretation. To mitigate this
      effect, we propose a surrogate of the fluorescence yield, namely the Canopy Cover
      Fluorescence Index (CCFI) that accounts for the spatial variability in canopy
      structure by exploiting the vegetation fractional cover. It was found that
      spatial aggregation tended to mask the effective relationships, while the CCFI
      was still able to maintain this link. This study is a first attempt in
      interpreting the fluorescence variability in aging forest stands and it may open
      new perspectives in understanding long-term forest dynamics in response to future
      climatic conditions from remote sensing of SIF.

PMID- 29460468
TI  - Review of the role of leptin in the regulation of male reproductive function.
AB  - Since discovered in 1994, leptin has been thought to be a pleiotropic hormone
      that regulates food intake, controls energy balance in the body and influences
      multiple tissues in the body. Leptin plays an important mediating role in the
      regulation of neuroendocrine and can transmit the nutritional status signals to
      the reproductive-related central nervous system. Many studies have shown that
      leptin may play an important role in the control of reproductive function. Leptin
      can act on all levels of the hypothalamus-pituitary-gonadal (HPG) axis and may
      have local effects on the function of testis and spermatogenesis. Leptin is
      critical for puberty initiation and can also modulate testosterone synthesis by
      downregulating cAMP-dependent activation of steroidogenic genes expressions.
      Leptin is found to be higher in infertile men than in normal subjects. Yet, the
      exact role of leptin in the regulation of male reproductive function remains
      incomplete. The purpose of this review was to summarise the recent research about
      the biological effects of leptin on male reproductive system. In-depth study of
      leptin in reproductive system will help to reveal the pathogenesis of infertility
      and provide new treatment ideas for human assisted reproductive technology.

PMID- 29460469
TI  - Further delineation of an entity caused by CREBBP and EP300 mutations but not
      resembling Rubinstein-Taybi syndrome.
AB  - In 2016, we described that missense variants in parts of exons 30 and 31 of
      CREBBP can cause a phenotype that differs from Rubinstein-Taybi syndrome (RSTS).
      Here we report on another 11 patients with variants in this region of CREBBP
      (between bp 5,128 and 5,614) and two with variants in the homologous region of
      EP300. None of the patients show characteristics typical for RSTS. The variants
      were detected by exome sequencing using a panel for intellectual disability in
      all but one individual, in whom Sanger sequencing was performed upon clinical
      recognition of the entity. The main characteristics of the patients are
      developmental delay (90%), autistic behavior (65%), short stature (42%), and
      microcephaly (43%). Medical problems include feeding problems (75%), vision
      (50%), and hearing (54%) impairments, recurrent upper airway infections (42%),
      and epilepsy (21%). Major malformations are less common except for cryptorchidism
      (46% of males), and cerebral anomalies (70%). Individuals with variants between
      bp 5,595 and 5,614 of CREBBP show a specific phenotype (ptosis, telecanthi, short
      and upslanted palpebral fissures, depressed nasal ridge, short nose, anteverted
      nares, short columella, and long philtrum). 3D face shape demonstrated
      resemblance to individuals with a duplication of 16p13.3 (the region that
      includes CREBBP), possibly indicating a gain of function. The other affected
      individuals show a less specific phenotype. We conclude that there is now more
      firm evidence that variants in these specific regions of CREBBP and EP300 result
      in a phenotype that differs from RSTS, and that this phenotype may be
      heterogeneous.

PMID- 29460470
TI  - The inspired sine-wave technique: A novel method to measure lung volume and
      ventilatory heterogeneity.
AB  - NEW FINDINGS: What is the central question of this study? We present a new non
      invasive medical technology, the inspired sine-wave technique, which involves
      inhalation of sinusoidally fluctuating concentrations of a tracer gas. The
      technique requires only passive patient cooperation and can monitor different
      cardiorespiratory variables, such as end-expired lung volume, ventilatory
      heterogeneity and pulmonary blood flow. What is the main finding and its
      importance? In this article, we demonstrate that the measurements of end-expired
      lung volume are repeatable and accurate, in comparison to whole-body
      plethysmography, and the technique is sensitive to the changes in ventilatory
      heterogeneity associated with advancing age. As such, it has the potential to
      provide clinically valuable information. ABSTRACT: The inspired sine-wave
      technique (IST) is a new method that can provide simple, non-invasive
      cardiopulmonary measurements. Over successive tidal breaths, the concentration of
      a tracer gas (i.e. nitrous oxide, N2 O) is sinusoidally modulated in inspired
      air. Using a single-compartment tidal-ventilation lung model, the resulting
      amplitude/phase of the expired sine wave allows estimation of end-expired lung
      volume (ELV), pulmonary blood flow and three indices for ventilatory
      heterogeneity (VH; ELV180 /FRCpleth , ELV180 /FRCpred and ELV60 /ELV180 ). This
      investigation aimed to determine the repeatability and agreement of ELV with
      FRCpleth and, as normal ageing results in well-established changes in pulmonary
      structure and function, whether the IST estimates of ELV and VH are age
      dependent. Forty-eight healthy never-smoker participants (20-86 years) underwent
      traditional pulmonary function testing (e.g. spirometry, body plethysmography)
      and the IST test, which consisted of 4 min of quiet breathing through a face mask
      while inspired N2 O concentrations were oscillated in a sine-wave pattern with a
      fixed mean (4%) and amplitude (3%) and a period of either 180 or 60 s. The ELV180
      /FRCpleth and ELV180 /FRCpred were age dependent (average decreases of 0.58 and
      0.48% year-1 ), suggesting an increase in VH with advancing age. The ELV showed a
      mean bias of -1.09 litres versus FRCpleth , but when normalized for the effects
      of age this bias reduced to -0.35 litres. The IST test has potential to provide
      clinically useful information necessitating further study (e.g. for mechanically
      ventilated or obstructive lung disease patients), but these findings suggest that
      the increases in VH with healthy ageing must be taken into account in clinical
      investigations.

PMID- 29460471
TI  - Generation of anti-porcine CD69 monoclonal antibodies and their usefulness to
      evaluate early activation of cellular immunity by flow cytometric analysis.
AB  - T cell-mediated cellular immunity and humoral immunity are equally important for
      the prevention of diseases. To assess activation of human and mouse cellular
      immunity, early activation markers of lymphocytes are often used in flow
      cytometry targeting expression of CD69 molecules. Response of humoral immunity
      against infection or vaccination has been well investigated in pigs, but that of
      cellular immunity has been largely neglected due to lack of direct evaluation
      tools. Thus, in pig research a proper assay of antibody reacted with porcine CD69
      is still unavailable. In the present study, two anti-porcine CD69 mAb-producing
      mouse hybridomas, 01-14-22-51 (IgG2b-kappa) and 01-22-44-102 (IgG2a-kappa), both
      showing fine reactivity with phorbol 12-myristate 13-acetate (PMA) and ionomycin
      stimulated porcine peripheral blood lymphocytes in flow cytometry, were
      established. When porcine peripheral blood lymphocytes were activated with PMA
      and ionomycin and analyzed by flow cytometry, it was found that both mAbs
      generated in this study stained about 70% of lymphocytes. In contrast, after an
      identical procedure, only 5% and 13.5% of lymphocytes were stained with anti
      interferon-gamma mAb and anti-tumor necrosis factor-alpha mAb, respectively.
      These results indicate that evaluation of cellular immunity activation turns more
      sensitive after using our newly generated mAbs.

PMID- 29460472
TI  - Dual-Native Vacancy Activated Basal Plane and Conductivity of MoSe2 with High
      Efficiency Hydrogen Evolution Reaction.
AB  - Although transition metal dichalcogenide MoSe2 is recognized as one of the low
      cost and efficient electrocatalysts for the hydrogen evolution reaction (HER),
      its thermodynamically stable basal plane and semiconducting property still hamper
      the electrocatalytic activity. Here, it is demonstrated that the basal plane and
      edges of 2H-MoSe2 toward HER can be activated by introducing dual-native vacancy.
      The first-principle calculations indicate that both the Se and Mo vacancies
      together activate the electrocatalytic sites in the basal plane and edges of
      MoSe2 with the optimal hydrogen adsorption free energy (DeltaGH* ) of 0 eV.
      Experimentally, 2D MoSe2 nanosheet arrays with a large amount of dual-native
      vacancies are fabricated as a catalytic working electrode, which possesses an
      overpotential of 126 mV at a current density of 100 mV cm-2 , a Tafel slope of 38
      mV dec-1 , and an excellent long-term durability. The findings pave a rational
      pathway to trigger the activity of inert MoSe2 toward HER and also can be
      extended to other layered dichalcogenide.

PMID- 29460473
TI  - When a physician and a clinical ethicist collaborate for better patient care.
AB  - Bioethics is a relatively new addition to bedside medical care in Arab world
      which is characterized by a special culture that often makes blind adaptation of
      western ethics codes and principles; a challenge that has to be faced. To date,
      the American University of Beirut Medical Center is the only hospital that offers
      bedside ethics consultations in the Arab Region aiming towards better patient
      centered care. This article tackles the role of the bedside clinical ethics
      consultant as an active member of the medical team and the impact of such
      consultations on decision-making and patient-centered care. Using the case of a
      child with multiple medical problems and a futile medical condition, we describe
      how the collaboration of the medical team and the clinical ethics consultant took
      a comprehensive approach to accompany and lead the parents and the medical team
      in their decision-making process and how the consultations allowed several
      salient issues to be addressed. This approach proved to be effective in the Arab
      cultural setting and indeed did lead to better patientcentered care.

PMID- 29460476
TI  - Chloroquine-induced cardiomyopathy: a reversible cause of heart failure.
AB  - Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-rheumatic medications
      frequently used in the treatment of connective tissue disorders. We present the
      case of a 45-year-old woman with CQ-induced cardiomyopathy leading to severe
      heart failure. Electrocardiographic abnormalities included bifascicular block,
      while structural disease consisted of severe biventricular and biatrial
      hypertrophy. Appropriate diagnosis via endomyocardial biopsy led to cessation of
      CQ and subsequent dramatic improvement in symptoms and structural heart disease.
      Cardiac toxicity is an under-recognized adverse effect of CQ/HCQ leading to
      cardiomyopathy with concentric hypertrophy and conduction abnormalities, with the
      potential for significant morbidity and mortality. Predisposing factors for
      CQ/HCQ-induced cardiomyopathy have been proposed. CQ/HCQ cardiomyopathy is a
      phenocopy of Fabry disease, and alpha-galactosidase A polymorphism may account
      for some heterogeneity of disease presentation.

PMID- 29460474
TI  - Specific synbiotics in early life protect against diet-induced obesity in adult
      mice.
AB  - AIMS: The metabolic state of human adults is associated with their gut
      microbiome. The symbiosis between host and microbiome is initiated at birth, and
      early life microbiome perturbation can disturb health throughout life. Here, we
      determined how beneficial microbiome interventions in early life affect metabolic
      health in adulthood. METHODS: Postnatal diets were supplemented with either
      prebiotics (scGOS/lcFOS) or synbiotics (scGOS/lcFOS with Bifidobacterium breve M
      16 V) until post-natal (PN) day 42 in a well-established rodent model for
      nutritional programming. Mice were subsequently challenged with a high-fat
      Western-style diet (WSD) for 8 weeks. Body weight and composition were monitored,
      as was gut microbiota composition at PN21, 42 and 98. Markers of glucose
      homeostasis, lipid metabolism and host transcriptomics of 6 target tissues were
      determined in adulthood (PN98). RESULTS: Early life synbiotics protected mice
      against WSD-induced excessive fat accumulation throughout life, replicable in 2
      independent European animal facilities. Adult insulin sensitivity and
      dyslipidaemia were improved and most pronounced changes in gene expression were
      observed in the ileum. We observed subtle changes in faecal microbiota
      composition, both in early life and in adulthood, including increased abundance
      of Bifidobacterium. Microbiota transplantation using samples collected from
      synbiotics-supplemented adolescent mice at PN42 to age-matched germ-free
      recipients did not transfer the beneficial phenotype, indicating that synbiotics
      modified microbiota at PN42 is not sufficient to transfer long-lasting protection
      of metabolic health status. CONCLUSION: Together, these findings show the
      potential and importance of timing of synbiotic interventions in early life
      during crucial microbiota development as a preventive measure to lower the risk
      of obesity and improve metabolic health throughout life.

PMID- 29460477
TI  - A pilot evaluation of a novel First Episode and Rapid Early Intervention service
      for Eating Disorders (FREED).
AB  - This pilot study assesses the impact of FREED (First Episode Rapid Early
      Intervention for Eating Disorders [ED]), a novel transdiagnostic service for
      emerging adults with recent ED onset, on clinical outcomes. Data were collected
      from 56 patients and 19 carers for 12 months following enrolment. FREED patients
      showed significant improvements in ED and other symptoms across time. Carers also
      showed psychological improvements. For FREED anorexia nervosa (AN) patients, body
      mass index (BMI) at initial clinical assessment was similar to that of comparable
      patients (audit cohort) seen in our service before (16.4 vs 16.1 kg/m2 ). By
      start of treatment, because of their shorter wait, FREED-AN had gained weight
      whereas audit patients had lost (16.7 vs 15.8 kg/m2 ). This difference continued
      throughout treatment, and at 12 months, nearly 60% FREED-AN patients returned to
      a BMI of 18.5 or greater. FREED shows promise as a service model for emerging
      adults with EDs.

PMID- 29460479
TI  - Label-Free Quantitative Phosphoproteomics Reveals Regulation of Vasodilator
      Stimulated Phosphoprotein upon Stathmin-1 Silencing in a Pair of Isogenic
      Colorectal Cancer Cell Lines.
AB  - In this communication, we present the phosphoproteome changes in an isogenic pair
      of colorectal cancer cell lines, viz., the poorly metastatic HCT-116 and the
      highly metastatic derivative E1, upon stathmin-1 (STMN1) knockdown. The aim was
      to better understand how the alterations of the phosphoproteins in these cells
      are involved in cancer metastasis. After the phosphopeptides were enriched using
      the TiO2 HAMMOC approach, comparative proteomics analysis was carried out using
      sequential window acquisition of all theoretical mass spectra-MS. Following
      bioinformatics analysis using MarkerView and OneOmics platforms, we identified a
      list of regulated phosphoproteins that may play a potential role in signaling,
      maintenance of cytoskeletal structure, and focal adhesion. Among these
      phosphoproteins, was the actin cytoskeleton regulator protein, vasodilator
      stimulated phosphoprotein (VASP), where its change in phosphorylation status was
      found to be concomitant with STMN1-associated roles in metastasis. We further
      showed that silencing of stathmin-1 altered the expression, subcellular
      localization and phosphorylation status of VASP, which suggested that it might be
      associated with remodeling of the cell cytoskeleton in colorectal cancer
      metastasis.

PMID- 29460478
TI  - Routine germline BRCA1 and BRCA2 testing in patients with ovarian carcinoma:
      analysis of the Scottish real-life experience.
AB  - OBJECTIVE: To determine the rates of germline BRCA1 and BRCA2 mutations in
      Scottish patients with ovarian cancer, before and after a change in testing
      policy. DESIGN: Retrospective cohort study. SETTING: Four cancer/genetics centres
      in Scotland. POPULATION: Patients with ovarian cancer undergoing germline BRCA1
      and BRCA2 (gBRCA1/2) sequencing before 2013 (under the 'old criteria', with
      selection based solely on family history), after 2013 (under the 'new criteria',
      with sequencing offered to newly presenting patients with non-mucinous ovarian
      cancer), and in the 'prevalent population' (who presented before 2013, but were
      not eligible for sequencing under the old criteria but were sequenced under the
      new criteria). METHODS: Clinicopathological and sequence data were collected
      before and for 18 months after this change in selection criteria. MAIN OUTCOME
      MEASURES: Frequency of germline BRCA1, BRCA2, RAD51C, and RAD51D mutations.
      RESULTS: Of 599 patients sequenced, 205, 236, and 158 were in the 'old criteria',
      'new criteria', and 'prevalent' populations, respectively. The frequency of
      gBRCA1/2 mutations was 30.7, 13.1, and 12.7%, respectively. The annual rate of
      gBRCA1/2 mutation detection was 4.2 before and 20.7 after the policy change. A
      total of 48% (15/31) 'new criteria' patients with gBRCA1/2 mutations had a
      Manchester score of <15 and would not have been offered sequencing based on
      family history criteria. In addition, 20 patients with gBRCA1/2 were identified
      in the prevalent population. The prevalence of gBRCA1/2 mutations in patients
      aged >70 years was 8.2%. CONCLUSIONS: Sequencing all patients with non-mucinous
      ovarian cancer gives a much higher annual gBRCA1/2 mutation detection rate, with
      the frequency of positive tests still exceeding the 10% threshold upon which many
      family history-based models operate. TWEETABLE ABSTRACT: BRCA sequencing all non
      mucinous cancer patients increases mutation detection five fold.

PMID- 29460480
TI  - Forty years of referrals and outcomes to a UK Child Development Centre (CDC): Has
      demand plateaued?
AB  - AIMS: To explore 40 years of Child Development Centre (CDC) activity and outcomes
      at Northampton General Hospital 1974-2014. METHODS: The study comprises 3 data
      sets: a published report from 1974 to 1999, an internal audit from 2001 to 2004,
      and more recent data collected from 2005 to 2014. The medical notes of all
      children who were assessed by the CDC in 2014 were reviewed, along with referral
      data collected by the CDC manager from this year and the preceding 10 years.
      RESULTS: From January 1, 1974 to December 31, 2014, 3,786 children were assessed.
      The male to female ratio is 2.8:1 from 2005 to 2014. Referrals for behavioural
      difficulties increased from 10% (10/100 referrals) in 1999-2004 to 17.8% (18/101
      referrals) in 2014. Similarly, referrals for social and communication problems,
      "interaction" increased two and a half fold from 10% (10/100 referrals) in 1999
      2004 to 26.7% (27/101 referrals) in 2014. Between 2004 and 2014, numbers of
      referrals for "developmental delay" halved (22.2% to 12%). CONCLUSION: We are
      aware of no other comparable extant UK CDC database. Services should plan for a
      referral rate of 6.5 per 1,000 preschool children. Between 1974 and 2014, there
      has clearly been a change in recorded assessment outcomes. From the mid-1980s,
      this reflects the change to a preschool assessment role and a shift away from
      purely educational outcome to include medical conditions. Covering 1974-2014, we
      demonstrate a clear increase in the number of referrals together with an
      increasing demand for assessments for social interaction and behavioural
      difficulties. This reflects the increased awareness of these neurodevelopmental
      difficulties and the changing diagnostic criteria which will now more likely
      result in an Autistic Spectrum Disorder diagnosis than previously. Together,
      these two features are most likely to have considerable implications for service
      development within Child Development Centres (CDCs) and Child Development Teams
      (CDTs).

PMID- 29460481
TI  - Evaluation of the benefit and use of the new terminology in endometrial cytology
      reporting system.
AB  - OBJECTIVE: The introduction and establishment of a new classification system for
      endometrial cytology, the "New Terminology in Endometrial Cytology (NTEMC)
      system," which is based on the Bethesda System for uterine cervical cytology, has
      recently been reported. However, the clinical management for new categories in
      the NTEMC system, particularly atypical endometrial cells (ATEC), has not been
      clarified. The objective of the present study is to determine how the ATEC
      category should be treated and whether the introduction of the system has
      decreased the number of unnecessary endometrial biopsies. METHODS: Fifty-nine
      cases were diagnosed as "suspicious positive" according to the three-tier
      reporting (TTR) system, which was adopted in Japan. The specimens were re
      evaluated according to the NTEMC system. Thirty-seven of the 59 patients
      underwent endometrial biopsy. We correlated the pathological diagnosis with the
      NTEMC system category. RESULTS: The 59 cases were classified according to the
      NTEMC system as follows: 36 cases were classified as ATEC of undetermined
      significance (ATEC-US), 21 cases were classified as ATEC for which atypical
      endometrial hyperplasia or worse cannot be excluded (ATEC-A), and 2 cases were
      classified as endometrial hyperplasia. The ratio of atypical endometrial
      hyperplasia or malignancy in ATEC-US category was significantly lower than that
      in ATEC-A category. Fifteen cases in ATEC-US category did not show atypical
      endometrial hyperplasia lesions or malignancy after 3 months. CONCLUSIONS: These
      data suggest that patients with ATEC-US results can be followed up for at least
      three months, and the introduction of the NTEMC system decreased the number of
      unnecessary endometrial biopsies.

PMID- 29460482
TI  - Electrocorticographic high-gamma modulation with passive listening paradigm for
      pediatric extraoperative language mapping.
AB  - OBJECTIVE: This prospective study compared the topography of high-gamma
      modulation (HGM) during a story-listening task requiring negligible patient
      cooperation, with the conventional electrical stimulation mapping (ESM) using a
      picture-naming task, for presurgical language localization in pediatric drug
      resistant epilepsy. METHODS: Patients undergoing extraoperative monitoring with
      subdural electrodes were included. Electrocorticographic signals were recorded
      during quiet baseline and a story-listening task. The likelihood of 70- to 150-Hz
      power modulation during the listening task relative to the baseline was estimated
      for each electrode and plotted on a cortical surface model. Sensitivity,
      specificity, accuracy, and diagnostic odds ratio (DOR) were estimated compared to
      ESM, using a meta-analytic framework. RESULTS: Nineteen patients (10 with left
      hemisphere electrodes) aged 4-19 years were analyzed. HGM during story listening
      was observed in bilateral posterior superior temporal, angular, supramarginal,
      and inferior frontal gyri, along with anatomically defined language association
      areas. Compared to either cognitive or both cognitive and orofacial sensorimotor
      interference with naming during ESM, left hemisphere HGM showed high specificity
      (0.82-0.84), good accuracy (0.66-0.70), and DOR of 2.23 and 3.24, respectively.
      HGM was a better classifier of ESM language sites in the left temporoparietal
      cortex compared to the frontal lobe. Incorporating visual naming with the story
      listening task substantially improved the accuracy (0.80) and DOR (13.61) of HGM
      mapping, while the high specificity (0.85) was retained. In the right hemisphere,
      no ESM sites for aphasia were seen, and the results of HGM and ESM comparisons
      were not significant. SIGNIFICANCE: HGM associated with story listening is a
      specific determinant of left hemisphere ESM language sites. It can be used for
      presurgical language mapping in children who cannot cooperate with conventional
      language tasks requiring active engagement. Incorporation of additional language
      tasks, if feasible, can further improve the diagnostic accuracy of language
      localization with HGM.

PMID- 29460483
TI  - Molecular cloning and expression analysis of tyr and tyrp1 genes in normal and
      albino yellow catfish Tachysurus fulvidraco.
AB  - The full-length complementary DNA of two genes related to vertebrate albinism,
      the tyrosinase gene tyr and tyrosinase-related protein 1 gene tyrp1, were cloned
      and analysed from normal and albino yellow catfish Tachysurus fulvidraco. The
      open reading frames (ORF) of tyr and tyrp1 encode putative peptides of 533 and
      526 amino acids (amino-acid), both of which possess two conserved copper binding
      sites. The homologous identities of deduced amino-acid sequences showed that both
      Tyr and Tyrp1 of T. fulvidraco share considerable similarity with that of channel
      catfish Ictalurus punctatus. Both tyr and tyrp1 were expressed in a wide range of
      adult tissues. Tyr gene had the highest expression level in the brain of both
      normal and albino T. fulvidraco. Tyrp1 had the highest expression level in the
      skin of normal groups, and the fin of albino groups. The messenger (m)RNA
      expressions of tyr and tyrp1 were detectable at different early developmental
      stages and varied with embryonic and larval growth. Tyr and tyrp1 mRNA have
      obvious tissue specificity both in normal and albino T. fulvidraco and higher
      expression levels were detected in the normal group revealing that tyr and tyrp1
      may have an important role in pigmentation. These results will provide useful
      data for understanding the molecular mechanism of melanin formation and the
      occurrence of albinism in T. fulvidraco.

PMID- 29460484
TI  - Sex-specific performance of pre-imaging diagnostic algorithms for pulmonary
      embolism.
AB  - : Essentials Decision rules for pulmonary embolism are used indiscriminately
      despite possible sex-differences. Various pre-imaging diagnostic algorithms have
      been investigated in several prospective studies. When analysed at an individual
      patient data level the algorithms perform similarly in both sexes. Estrogen use
      and male sex were associated with a higher prevalence in suspected pulmonary
      embolism. SUMMARY: Background In patients suspected of pulmonary embolism (PE),
      clinical decision rules are combined with D-dimer testing to rule out PE,
      avoiding the need for imaging in those at low risk. Despite sex differences in
      several aspects of the disease, including its diagnosis, these algorithms are
      used indiscriminately in women and men. Objectives To compare the performance,
      defined as efficiency and failure rate, of three pre-imaging diagnostic
      algorithms for PE between women and men: the Wells rule with fixed or with age
      adjusted D-dimer cut-off, and a recently validated algorithm (YEARS). A secondary
      aim was to determine the sex-specific prevalence of PE. Methods Individual
      patient data were obtained from six studies using the Wells rule (fixed D-dimer,
      n = 5; age adjusted, n = 1) and from one study using the YEARS algorithm. All
      studies prospectively enrolled consecutive patients with suspected PE. Main
      outcomes were efficiency (proportion of patients in which the algorithm ruled out
      PE without imaging) and failure rate (proportion of patients with PE not detected
      by the algorithm). Outcomes were estimated using (multilevel) logistic regression
      models. Results The main outcomes showed no sex differences in any of the
      separate algorithms. With all three, the prevalence of PE was lower in women (OR,
      0.66, 0.68 and 0.74). In women, estrogen use, adjusted for age, was associated
      with lower efficiency and higher prevalence and D-dimer levels. Conclusions The
      investigated pre-imaging diagnostic algorithms for patients suspected of PE show
      no sex differences in performance. Male sex and estrogen use are both associated
      with a higher probability of having the disease.

PMID- 29460485
TI  - Saudi Arabian children's reasoning about religion-based exclusion.
AB  - This study examined how Saudi Arabian children (M = 10.50 years, SD = 1.61, Range
      = 8-10 years) evaluate peer exclusion based on religion when the perpetrator of
      exclusion was a peer or a father. Children believed that it was more acceptable
      for fathers than for peers to enforce exclusion and were more likely to use
      social conventional reasons to justify exclusion when the perpetrator was a
      father. The discussion focuses on how social domain theory needs to take
      children's cultural community into account. Statement of contribution What is
      already known on this subject? Research suggests that children do not defer to
      authority in making decisions about peer exclusion. Children tend to believe that
      authority figures should not order peer exclusion because it is a moral decision.
      What does this study add? Unlike children in other collectivist countries,
      children in Saudi Arabia support peer exclusion ordered by a father more than a
      peer. Saudi children use social conventional reasoning to justify fathers'
      support for peer exclusion.

PMID- 29460486
TI  - 2 H-fractionations during the biosynthesis of carbohydrates and lipids imprint a
      metabolic signal on the delta2 H values of plant organic compounds.
AB  - Hydrogen (H) isotope ratio (delta2 H) analyses of plant organic compounds have
      been applied to assess ecohydrological processes in the environment despite a
      large part of the delta2 H variability observed in plant compounds not being
      fully elucidated. We present a conceptual biochemical model based on empirical H
      isotope data that we generated in two complementary experiments that clarifies a
      large part of the unexplained variability in the delta2 H values of plant organic
      compounds. The experiments demonstrate that information recorded in the delta2 H
      values of plant organic compounds goes beyond hydrological signals and can also
      contain important information on the carbon and energy metabolism of plants. Our
      model explains where 2 H-fractionations occur in the biosynthesis of plant
      organic compounds and how these 2 H-fractionations are tightly coupled to a
      plant's carbon and energy metabolism. Our model also provides a mechanistic basis
      to introduce H isotopes in plant organic compounds as a new metabolic proxy for
      the carbon and energy metabolism of plants and ecosystems. Such a new metabolic
      proxy has the potential to be applied in a broad range of disciplines, including
      plant and ecosystem physiology, biogeochemistry and palaeoecology.

PMID- 29460488
TI  - Effects of cell state and staining on femtosecond laser nanosurgery.
AB  - Femtosecond laser nanosurgery enables precise manipulation of subcellular
      elements to study regeneration. However, currently it is not frequently employed
      probably because of its unknown consequences on the whole cell level. To better
      understand the associated biological response of the cell, especially in the
      context of different cell states and cell staining, we manipulated C2C12
      myoblasts and myotubes, which were either unstained (nicotinamide adenine
      dinucleotide signal) or stained with MitoTracker Red. Both signals overlap well
      and stain similar areas in untreated cells. We chose 3 different cutting lengths
      and performed surgery in the cytosol along the major cell axis. The cuts resealed
      within several minutes independent of the cutting length. We analyzed cell area,
      perimeter, major and minor axis on long term. We observed significant changes in
      the cell area and perimeter, dependent on the staining and more pronounced in
      differentiated myotubes. We conclude, that laser parameters must be chosen
      carefully, depending on the staining of the cell, its (differentiation) state,
      and the extent of the cut region, such that unwanted cell responses can be
      avoided. Laser manipulation of C2C12 myotubes with small ablation (0.8 MUm) and
      large ablation (3.0 MUm). While small damages recover, larger damages lead to
      elimination from the syncytium. Scale bar: 20 MUm.

PMID- 29460487
TI  - Systematic review: probiotics in the management of lower gastrointestinal
      symptoms - an updated evidence-based international consensus.
AB  - BACKGROUND: In 2013, a systematic review and Delphi consensus reported that
      specific probiotics can benefit adult patients with irritable bowel syndrome
      (IBS) and other gastrointestinal (GI) problems. AIM: To update the consensus with
      new evidence. METHODS: A systematic review identified randomised, placebo
      controlled trials published between January 2012 and June 2017. Evidence was
      graded, previously developed statements were reassessed by an 8-expert panel, and
      agreement was reached via Delphi consensus. RESULTS: A total of 70 studies were
      included (IBS, 34; diarrhoea associated with antibiotics, 13; diarrhoea
      associated with Helicobacter pylori eradication therapy, 7; other conditions,
      16). Of 15 studies that examined global IBS symptoms as a primary endpoint, 8
      reported significant benefits of probiotics vs placebo. Consensus statements with
      100% agreement and "high" evidence level indicated that specific probiotics help
      reduce overall symptom burden and abdominal pain in some patients with IBS and
      duration/intensity of diarrhoea in patients prescribed antibiotics or H. pylori
      eradication therapy, and have favourable safety. Statements with 70%-100%
      agreement and "moderate" evidence indicated that, in some patients with IBS,
      specific probiotics help reduce bloating/distension and improve bowel movement
      frequency/consistency. CONCLUSIONS: This updated review indicates that specific
      probiotics are beneficial in certain lower GI problems, although many of the new
      publications did not report benefits of probiotics, possibly due to inclusion of
      new, less efficacious preparations. Specific probiotics can relieve lower GI
      symptoms in IBS, prevent diarrhoea associated with antibiotics and H. pylori
      eradication therapy, and show favourable safety. This study will help clinicians
      recommend/prescribe probiotics for specific symptoms.

PMID- 29460489
TI  - Exercise-induced pulmonary hemorrhage in barrel racing horses in the Pacific
      Northwest region of the United States.
AB  - BACKGROUND: Exercise-induced pulmonary hemorrhage (EIPH) refers to bleeding from
      the lungs in association with strenuous exercise. It has been documented in race
      horses but little information exists on EIPH in barrel racing horses.
      HYPOTHESIS/OBJECTIVES: Our goals were to evaluate the presence of EIPH in barrel
      racing horses and estimate its prevalence in the Pacific Northwest. ANIMALS: 149
      barrel racing horses enrolled at events in WA (11), ID (3), and MT (33). METHODS:
      Observational cross-sectional study. Data collected included signalment, history
      of illness, respiratory disease, race division, and pre-race medications.
      Endoscopy was performed and tracheobronchoscopic (TBE) EIPH score was assigned
      based on quantity of blood in the trachea (0 = no blood to 4 = abundance of blood
      within the trachea). After TBE, bronchoalveolar lavage (BAL) was performed.
      Erythrocyte (red blood cell, RBC) counts were obtained from bronchoalveolar
      lavage fluid (BALF). Statistical analysis included linear and logistic
      regression, Fisher's exact t test, and calculation of correlation coefficient.
      Significance was set at P < .05. RESULTS: The prevalence of EIPH based on TBE
      EIPH score was 54%. When based on BALF RBC count >1,000 cells, EIPH prevalence
      was 66%. Race time did not significantly affect the presence of EIPH. A
      significant (P < .0001) positive linear relationship between the TBE and BAL
      erythrocyte count was identified, but its strength was poor (r2  = .15).
      CONCLUSIONS AND CLINICAL IMPORTANCE: EIPH occurs in over 50% of barrel racing
      horses in the Pacific Northwest. Precise determination of the impact of EIPH on
      health of barrel racers requires further study.

PMID- 29460491
TI  - Corrigendum.

PMID- 29460490
TI  - Evaluation of sex differences in the relationship between diastolic dysfunction
      and thromboembolism using propensity score analysis.
AB  - BACKGROUND: Female sex is a risk factor for thromboembolism (TE) in atrial
      fibrillation (AF); however, the underlying mechanisms are unclear. We postulated
      that left ventricular (LV) diastolic dysfunction (LVDD) could be associated with
      increased thromboembolic risk in women. METHODS: From a retrospective cohort, 158
      patients (female : male = 79:79) with nonvalvular AF were propensity score
      matched for age, presence of diabetes, hypertension, coronary artery disease,
      congestive heart failure, embolic history, AF type, and AF duration. Cardiac size
      and function and central aortic stiffness parameters were evaluated. Diastolic
      function was classified as normal, indeterminate, and LVDD according to recent
      guidelines. Surrogate markers for thromboembolism (dense spontaneous echo
      contrast and thrombus) were evaluated using transesophageal echocardiography.
      RESULTS: Surrogate markers for TE showed a trend to be more frequent in women
      than in men (21.5% vs 11.4%, P = .086). LVDD was more prevalent in women than in
      men (22.8% vs 2.5%, P < .001); however, the prevalence of indeterminate diastolic
      function was not different between sexes (26.6% vs 20.3%, P = .453). Surrogate
      markers for TE were detected mostly in women with LVDD. LV diastolic parameters
      showed a restrictive pattern, and aortic stiffness parameters were worse in women
      than in men. Women with LVDD had increased aortic stiffness compared to women
      with indeterminate and normal function, whereas aortic stiffness did not differ
      among men in all groups. Significant relations between LV diastolic function and
      aortic stiffness parameters were observed only in women. CONCLUSION: LVDD due to
      increased aortic stiffness could be related to a higher thromboembolic risk in
      women with AF.

PMID- 29460493
TI  - Changes at Molecular Microbiology for 2018.

PMID- 29460492
TI  - Cerebrospinal fluid Lyme multiplex assay results are not diagnostic in horses
      with neuroborreliosis.
AB  - BACKGROUND: The accuracy of the Lyme multiplex assay for the diagnosis of
      neuroborreliosis in horses is unknown. HYPOTHESIS/OBJECTIVES: To describe Lyme
      multiplex results in horses with a postmortem diagnosis of neuroborreliosis. The
      hypothesis was that paired serum and cerebrospinal fluid (CSF) results and a CSF
      : serum ratio would allow differentiation of horses with neuroborreliosis from
      those with other neurologic diseases. ANIMALS: Ninety horses that had neurologic
      examinations, serum and CSF Lyme multiplex analyses, and postmortem examination
      of the nervous system performed. METHODS: Retrospective study. Data collected
      included signalment, ante- and postmortem diagnoses, and serum and CSF Lyme
      multiplex results. The CSF : serum ratio was calculated by dividing CSF median
      fluorescent intensity (MFI) by serum MFI for each result. RESULTS: Ten horses had
      a final diagnosis of neuroborreliosis, 70 were diagnosed with other neurologic
      diseases, and 10 had no neurologic disease. Not all horses with neuroborreliosis
      had positive results: 4/10 had at least 1 positive serum result, 5/10 had at
      least 1 positive CSF result, and 3/10 had at least 1 CSF result 4-fold higher
      than the corresponding serum result. Results were similar for the 70 horses with
      other neurologic diseases: 53% had at least 1 positive serum result, 50% had at
      least 1 positive CSF result, and 16% had at least 1 CSF result 4-fold higher than
      the corresponding serum result. CONCLUSIONS AND CLINICAL IMPORTANCE: Positive
      Lyme multiplex results were common in horses with neurologic diseases and did not
      adequately differentiate horses with neuroborreliosis from horses with other
      disorders.

PMID- 29460494
TI  - The effects of prescribing varenicline on two-year health outcomes: an
      observational cohort study using electronic medical records.
AB  - AIMS: To investigate whether smokers prescribed varenicline had lower risks of
      serious ill-health during the 4 years following treatment compared with those
      prescribed nicotine replacement therapy (NRT). DESIGN: Observational cohort study
      of electronic medical records. SETTING: A total of 370 UK general practices
      sampled from the Clinical Practice Research Datalink. PARTICIPANTS: A total of
      126 718 patients aged 18 and over who were issued smoking cessation prescriptions
      between 1 September 2006 and 31 March 2014. MEASUREMENTS: Our primary outcome was
      all-cause mortality within 2 years of first prescription as indicated by linked
      Office of National Statistics data. Our secondary outcomes were cause-specific
      mortality, all-cause, cause-specific hospitalization, primary care diagnosis of
      myocardial infarction or chronic obstructive pulmonary disease (COPD), body mass
      index and attendance rate to primary care within 2 years of first prescription.
      Risk differences and 95% confidence intervals were estimated by multivariable
      adjusted regression and propensity score matched regression. We used instrumental
      variable analysis to overcome residual confounding. FINDINGS: People prescribed
      varenicline were healthier at baseline than those prescribed NRT in almost all
      characteristics, highlighting the potential for residual confounding. Our
      instrumental variable analysis results found that people prescribed varenicline
      had a similar risk of mortality at 2 years [risk difference per 100 patients
      treated = 0.67, 95% confidence interval (CI) = -0.11 to 1.46)] to those
      prescribed NRT, and there were similar rates of all-cause hospitalization,
      incident primary-care diagnoses of myocardial infarction and COPD. People
      prescribed varenicline subsequently attended primary care less frequently.
      CONCLUSIONS: Smokers prescribed varenicline in primary care in the United Kingdom
      do not appear to be less likely to die, be hospitalized or experience a
      myocardial infarction or chronic obstructive pulmonary disease during the
      following 2 years compared with smokers prescribed nicotine replacement therapy,
      but they gain more weight and attend primary care less frequently.

PMID- 29460496
TI  - When things don't add up: quantifying impacts of multiple stressors from
      individual metabolism to ecosystem processing.
AB  - Ecosystems are exposed to multiple stressors which can compromise functioning and
      service delivery. These stressors often co-occur and interact in different ways
      which are not yet fully understood. Here, we applied a population model
      representing a freshwater amphipod feeding on leaf litter in forested streams. We
      simulated impacts of hypothetical stressors, individually and in pairwise
      combinations that target the individuals' feeding, maintenance, growth and
      reproduction. Impacts were quantified by examining responses at three levels of
      biological organisation: individual-level body sizes and cumulative reproduction,
      population-level abundance and biomass and ecosystem-level leaf litter
      decomposition. Interactive effects of multiple stressors at the individual level
      were mostly antagonistic, that is, less negative than expected. Most population-
      and ecosystem-level responses to multiple stressors were stronger than expected
      from an additive model, that is, synergistic. Our results suggest that across
      levels of biological organisation responses to multiple stressors are rarely only
      additive. We suggest methods for efficiently quantifying impacts of multiple
      stressors at different levels of biological organisation.

PMID- 29460495
TI  - Association between sleep-disordered breathing and arterial stiffness in heart
      failure patients with reduced or preserved ejection fraction.
AB  - AIMS: Sleep-disordered breathing (SDB) is associated with arterial stiffness,
      which may be one of the factors that lead to heart failure (HF). We examined the
      relationship between pulse wave velocity (PWV) and SDB in patients who have HF
      with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction
      (HFpEF). METHODS AND RESULTS: We measured the apnoea-hypopnoea index (AHI) by
      polysomnography, echocardiographic parameters, and PWV in 221 HF patients. Age,
      blood pressure, and PWV were higher in HFpEF (ejection fraction > 50%, n = 70)
      patients than in HFrEF (ejection fraction < 50%, n = 151) patients. All HF
      patients were divided into three groups according to AHI: none-to-mild SDB group
      (AHI < 15 times/h, n = 77), moderate SDB group (15 < AHI < 30 times/h, n = 59),
      and severe SDB group (AHI > 30 times/h, n = 85). Although blood pressure and
      echocardiographic parameters did not differ among the three groups, PWV was
      significantly higher in the severe SDB group than in the none-to-mild and
      moderate SDB groups (P = 0.002). When the HFrEF and HFpEF patients were analysed
      separately, PWV was significantly higher in the severe SDB group than in the none
      to-mild and moderate SDB groups in patients with HFpEF (P = 0.002), but not in
      those with HFrEF (P = 0.068). In the multiple regression analysis to determine
      PWV, the presence of severe SDB was found to be an independent predictor of high
      PWV in HFpEF (beta = 0.234, P = 0.005), but not in HFrEF patients. CONCLUSIONS:
      Severe SDB is associated with elevated arterial stiffness and may be related to
      the pathophysiology of HF, especially in HFpEF patients.

PMID- 29460497
TI  - Atomically Dispersed Metal Sites in MOF-Based Materials for Electrocatalytic and
      Photocatalytic Energy Conversion.
AB  - Metal sites play an essential role in both electrocatalytic and photocatalytic
      energy conversion. The highly ordered arrangements of the organic linkers and
      metal nodes as well as the well-defined pore structures of metal-organic
      frameworks (MOFs) make them ideal substrates to support atomically dispersed
      metal sites (ADMSs) located in their metal nodes, linkers, and pores. Porous
      carbon materials doped with ADMSs can be derived from these ADMS-incorporating
      MOF precursors through controlled treatments. These ADMSs incorporated in
      pristine MOFs and MOF-derived carbon materials possess unique advantages over
      molecular or bulk metal-based catalysts and bridge the gap between homogeneous
      and heterogeneous catalysts for energy-conversion applications. This Review
      presents recent progress in the design and incorporation of ADMSs in MOFs and MOF
      derived materials for energy-conversion applications.

PMID- 29460499
TI  - Implications of Odera Oruka's ethics of consumerism for reducing globesity.
AB  - In this paper, I advance Odera Oruka's insights on the ethics of consumerism in
      order to draw relevant implications of his thoughts on rethinking the problem of
      obesity. I argue that Oruka's ethics of consumerism and his right to human
      minimum theory entail some salient ideas that might serve as a better ethical
      model for reducing the global obesity prevalence. Though Oruka's African moral
      philosophy is yet to receive universal attention it arguably deserves, the
      interests of the international and 'globesity' community would be better served
      learning from the contributions of an African moral theory to contemporary
      bioethical discourse on obesity. Oruka's moral thoughts are by constitution, a
      deontological and cosmopolitan call for reducing hunger in globalized world,
      while also indirectly, addressing obesity of the poor. I show the limitations of
      his ethics of consumerism, and the shortcomings of such ethics in the context of
      obesity of the poor. Consequently, I develop a neo-Orukan virtue based ethics
      that is worthy of attention in efforts towards addressing the obesity tide. No
      such perspective currently exists in the context of obesity; yet the exigent need
      for one is necessitated by the defects of the libertarian and harm principle
      approaches in Western bioethical discourse.

PMID- 29460498
TI  - The molecular epidemiology of Huntington disease is related to intermediate
      allele frequency and haplotype in the general population.
AB  - Huntington disease (HD) is the most common monogenic neurodegenerative disorder
      in populations of European ancestry, but occurs at lower prevalence in
      populations of East Asian or black African descent. New mutations for HD result
      from CAG repeat expansions of intermediate alleles (IAs), usually of paternal
      origin. The differing prevalence of HD may be related to the rate of new
      mutations in a population, but no comparative estimates of IA frequency or the HD
      new mutation rate are available. In this study, we characterize IA frequency and
      the CAG repeat distribution in fifteen populations of diverse ethnic origin. We
      estimate the HD new mutation rate in a series of populations using molecular IA
      expansion rates. The frequency of IAs was highest in Hispanic Americans and
      Northern Europeans, and lowest in black Africans and East Asians. The prevalence
      of HD correlated with the frequency of IAs by population and with the proportion
      of IAs found on the HD-associated A1 haplotype. The HD new mutation rate was
      estimated to be highest in populations with the highest frequency of IAs. In
      European ancestry populations, one in 5,372 individuals from the general
      population and 7.1% of individuals with an expanded CAG repeat in the HD range
      are estimated to have a molecular new mutation. Our data suggest that the new
      mutation rate for HD varies substantially between populations, and that IA
      frequency and haplotype are closely linked to observed epidemiological
      differences in the prevalence of HD across major ancestry groups in different
      countries.

PMID- 29460500
TI  - Auto- and alloantibodies against factor XIII: laboratory diagnosis and clinical
      consequences.
AB  - Acquired FXIII deficiencies caused by autoantibodies against FXIII subunits
      represent rare but very severe bleeding diatheses. Alloantibodies in FXIII
      deficient patients also cause life-threatening bleeding complications, but they
      develop extremely rarely. In this review we provide an overview of the diagnosis
      and classification of anti-FXIII antibodies and analyze 48 patients with
      autoimmune FXIII deficiency and four additional FXIII-deficient patients who
      developed anti-FXIII alloantibody. The patients were collected from peer-reviewed
      publications from which relevant data could be extracted. With the exception of
      two cases the antibodies were directed against FXIII-A. The difficulties in the
      diagnosis of FXIII deficiency in the presence of anti-FXIII antibodies are
      discussed and a scheme for the functional classification of the anti-FXIII
      antibodies is recommended. The three main categories are neutralizing and non
      neutralizing antibodies and antibodies with combined effect. The methods being
      used for detecting and quantifying the inhibitory effect on FXIII activation and
      on the transglutaminase activity of activated FXIII are summarized and techniques
      for the classification of neutralizing anti-FXIII antibodies are outlined. The
      importance of clearance studies in these cases is emphasized. Binding assays,
      useful for the identification of non-neutralizing and combined type antibodies,
      were collected from the literature and their informative power is demonstrated by
      examples. The most frequently occurring bleeding symptoms in patients with anti
      FXIII antibodies were soft tissue bleeding; intracranial bleedings also occurred,
      but less frequently than in inherited FXIII deficiency. Treatment of such
      patients is extremely challenging; the main aim should be eradication of the
      antibody.

PMID- 29460501
TI  - Implementation of a new patient education programme for renal transplant
      recipients.
AB  - BACKGROUND: Nurses' strategies regarding patient education should be informed by
      the best available research evidence. Clinical nurses play an essential role in
      implementing new patient education programmes for renal transplant recipients.
      AIM: This study investigated transplant nurse job satisfaction, competence,
      training and perceptions of quality of care in relation to the implementation of
      a new, evidence-based, patient education programme. This paper reports the
      results from the first part of an implementation study. METHODS: Data were
      collected in the form of a survey from 50 clinical transplant nurses at a single
      national transplant centre in Norway in 2015, six months after the patient
      education programme was implemented. A descriptive, cross-sectional design was
      used. RESULTS: Seventy-two percent of the respondents reported that they had
      sufficient knowledge about the new programme; 54.4 % stated that the new
      programme resulted in renal transplant recipients being better educated. The new
      programme was found to be more structured, patient-centered and visible for the
      nurses across the wards, as compared with their previous practice. Nurses with
      less nursing experience were significantly more motivated about the new patient
      education programme, than the more experienced nurses (p = 0.05). CONCLUSIONS:
      Nurses were generally satisfied with their new patient education practice.
      Knowledge derived from the research evidence on patient education was found to be
      valuable and transferable to everyday clinical nursing practice.

PMID- 29460502
TI  - Immediate biopsy of cervical cytology-negative and non-HPV-16/18 oncogenic types
      positive patients.
AB  - BACKGROUND: According to the American Society of Colposcopy and Cervical
      Pathology (ASCCP), a co-test is recommended for patients one year after the
      detection of non-HPV 16/18 viral types in association with a negative cervical
      cytology. In this study, we used immediate colposcopy to evaluate the risks to
      the patient during the one year waiting period. METHODS: We included 544 Hpv
      positive/cervical cytology-negative patients who underwent cervical cancer
      screening from June 2015 to June 2017. Cytological specimens were classified
      using the Bethesta method on a liquid based preparation. We used the Hybrid
      Capture 2 system to define HPV DNA. Biopsies were performed on all patients under
      colposcopy. RESULTS: Three hundred and seventy-five patients had HPV types 16/18
      and 169 had non-HPV-16/18 oncogenic types. Of the 169 patients who had non-HPV
      16/18 oncogenic types, 151 (89%) had no dysplasia, 16 (9.4%) had CIN 1, and 2
      (1.1%) had CIN 2/CIN 3. CONCLUSION: For the patients who had cervical cytology
      negative/non-HPV-16/18 positive, we detected that 1.1% of these women had CIN 2
      3. For this reason, by chasing the algorithm recommended by guidelines,
      gynecologists take risk missing a diagnosis of CIN 2 plus lesion in 1.1% of
      patients.

PMID- 29460503
TI  - Urinary liver-type fatty acid-binding protein in pediatric nephrotic syndrome and
      tubular dysfunction.
AB  - BACKGROUND: Urinary liver-type fatty acid-binding protein (uL-FABP) has recently
      been identified as a biomarker for kidney injury. uL-FABP excretion in pediatric
      relapsing nephrotic syndrome and tubular dysfunction, however, has not been
      reported previously. METHODS: We measured uL-FABP level in children with steroid
      sensitive nephrotic syndrome (SSNS), in those with tubular dysfunction, and in
      control subjects. RESULTS: uL-FABP was markedly increased in relapsing SSNS
      (median, 30.3 MUg/gCr; range, 12.6-171.0 MUg/gCr; n = 13), and also in the
      tubular dysfunction group (median, 164.8 MUg/gCr; range, 41.6-834.5 MUg/gCr; n =
      7), compared with the control subjects (median, 3.0 MUg/gCr; range, 1.1-13.9
      MUg/gCr; n = 21). uL-FABP level was significantly correlated with urinary protein
      excretion in the SSNS group, and in the total group. Additionally, in the SSNS
      group, elevated uL-FABP in the relapsing stage returned to a level similar to
      that in the control group on remission of NS. In the tubular dysfunction group,
      uL-FABP was significantly correlated with urinary beta2-microglobulin.
      CONCLUSION: Urinary protein amount, and the ability of the proximal tubules to
      reabsorb low-molecular-weight proteins, should also be considered when evaluating
      the clinical significance of uL-FABP as a biomarker for kidney injury in
      children.

PMID- 29460504
TI  - Node self-connections and metapopulation persistence: reply to Saura (2018).
AB  - Saura () claims that studies using the Probability of Connectivity metric (PC)
      had already demonstrated the importance of including node self-connections in
      network metrics. As originally defined and used, PC cannot test the importance of
      self-connections. However, with key terms redefined, PC could be a useful tool in
      future work.

PMID- 29460505
TI  - Identification of an algal xylan synthase indicates that there is functional
      orthology between algal and plant cell wall biosynthesis.
AB  - Insights into the evolution of plant cell walls have important implications for
      comprehending these diverse and abundant biological structures. In order to
      understand the evolving structure-function relationships of the plant cell wall,
      it is imperative to trace the origin of its different components. The present
      study is focused on plant 1,4-beta-xylan, tracing its evolutionary origin by
      genome and transcriptome mining followed by phylogenetic analysis, utilizing a
      large selection of plants and algae. It substantiates the findings by
      heterologous expression and biochemical characterization of a charophyte alga
      xylan synthase. Of the 12 known gene classes involved in 1,4-beta-xylan
      formation, XYS1/IRX10 in plants, IRX7, IRX8, IRX9, IRX14 and GUX occurred for the
      first time in charophyte algae. An XYS1/IRX10 ortholog from Klebsormidium
      flaccidum, designated K. flaccidumXYLAN SYNTHASE-1 (KfXYS1), possesses 1,4-beta
      xylan synthase activity, and 1,4-beta-xylan occurs in the K. flaccidum cell wall.
      These data suggest that plant 1,4-beta-xylan originated in charophytes and shed
      light on the origin of one of the key cell wall innovations to occur in
      charophyte algae, facilitating terrestrialization and emergence of polysaccharide
      based plant cell walls.

PMID- 29460506
TI  - Investigating the longitudinal association between diabetes and anxiety: a
      systematic review and meta-analysis.
AB  - AIM: Previous research has indicated an association between diabetes and anxiety.
      However, no synthesis has determined the direction of this association. The aim
      of this study was to determine the longitudinal relationship between anxiety and
      diabetes. METHODS: We searched seven databases for studies examining the
      longitudinal relationship between anxiety and diabetes. Two independent reviewers
      screened studies from a population aged 16 or older that examined either anxiety
      as a risk factor for incident diabetes or diabetes as a risk factor for incident
      anxiety. Studies that met eligibility criteria were put forward for data
      extraction and meta-analysis. RESULTS: In total 14 studies (n = 1 760 800) that
      examined anxiety as a risk factor for incident diabetes and two (n = 88 109) that
      examined diabetes as a risk factor for incident anxiety were eligible for
      inclusion in the review. Only studies examining anxiety as a risk factor for
      incident diabetes were put forward for the meta-analysis. The least adjusted
      (unadjusted or adjusted for age only) estimate indicated a significant
      association between baseline anxiety with incident diabetes (odds ratio 1.47,
      1.23-1.75). Furthermore, most-adjusted analyses indicated a significant
      association between baseline anxiety and incident diabetes. Included studies that
      examined diabetes to incident anxiety found no association. CONCLUSIONS: There
      was an association between baseline anxiety and incident diabetes. The results
      also indicate the need for more research to examine the direction of association
      from diabetes to incident anxiety. This work adds to the growing body of evidence
      that poor mental health increases the risk of developing diabetes.

PMID- 29460508
TI  - Predatory strategies and behaviours in cephalopods are altered by elevated CO2.
AB  - There is increasing evidence that projected near-future carbon dioxide (CO2 )
      levels can alter predator avoidance behaviour in marine invertebrates, yet little
      is known about the possible effects on predatory behaviours. Here we tested the
      effects of elevated CO2 on the predatory behaviours of two ecologically distinct
      cephalopod species, the pygmy squid, Idiosepius pygmaeus, and the bigfin reef
      squid, Sepioteuthis lessoniana. Both species exhibited an increased latency to
      attack and altered body pattern choice during the attack sequence at elevated CO2
      . I. pygmaeus also exhibited a 20% decrease in predation rate, an increased
      striking distance, and reduced preference for attacking the posterior end of prey
      at elevated CO2 . Elevated CO2 increased activity levels of S. lessoniana
      comparable to those previously shown in I. pygmaeus, which could adversely affect
      their energy budget and increase their potential to be preyed upon. The effects
      of elevated CO2 on predatory behaviours, predation strategies and activity levels
      of cephalopods reported here could have far-reaching consequences in marine
      ecosystems due to the ecological importance of cephalopods in the marine food
      web.

PMID- 29460507
TI  - Bloody-minded parasites and sex: the effects of fluctuating virulence.
AB  - Asexual lineages can grow at a faster rate than sexual lineages. Why then is
      sexual reproduction so widespread? Much empirical evidence supports the Red Queen
      hypothesis. Under this hypothesis, coevolving parasites favour sexual
      reproduction by adapting to infect common asexual clones and driving them down in
      frequency. One limitation, however, seems to challenge the generality of the Red
      Queen: in theoretical models, parasites must be very virulent to maintain sex.
      Moreover, experiments show virulence to be unstable, readily shifting in response
      to environmental conditions. Does variation in virulence further limit the
      ability of coevolving parasites to maintain sex? To address this question, we
      simulated temporal variation in virulence and evaluated the outcome of
      competition between sexual and asexual females. We found that variation in
      virulence did not limit the ability of coevolving parasites to maintain sex. In
      fact, relatively high variation in virulence promoted parasite-mediated
      maintenance of sex. With sufficient variation, sexual females persisted even when
      mean virulence fell well below the threshold virulence required to maintain sex
      under constant conditions. We conclude that natural variation in virulence does
      not limit the relevance of the Red Queen hypothesis for natural populations; on
      the contrary, it could expand the range of conditions over which coevolving
      parasites can maintain sex.

PMID- 29460509
TI  - Study of the efficacy of carboxytherapy in alopecia.
AB  - BACKGROUND: Management of alopecia areata (AA) and androgenetic alopecia (AGA) is
      often challenging. The use of carboxytherapy may be a novel therapeutic option
      for such cases. OBJECTIVE: To evaluate the clinical efficacy and safety of
      carboxytherapy in alopecia areata and androgenetic alopecia. PATIENTS AND
      METHODS: This study was conducted on 80 patients with alopecia divided into two
      groups; Group I included 40 AA patients (Group IA received carboxytherapy and
      Group IB control received placebo), and Group II included 40 AGA patients (Group
      IIA received carboxytherapy and Group IIB control received placebo), and followed
      up monthly for 3 months. They were evaluated clinically (by assessment of
      Severity of Alopecia Tool (SALT) score in group I, and Sinclair scale and Norwood
      Hamilton scale in group II), by dermoscopy and digital dermoscopy at each visit.
      RESULTS: Group IA patients showed significant clinical improvement in SALT score
      and dermoscopic improvement after carboxytherapy and at the end of follow-up
      period with significant reduction in dystrophic hair, black dots, yellow dots,
      and tapered hair coinciding with significant emergence of regrowing hair. Group
      IIA patients showed significant clinical and dermoscopic improvement after
      carboxytherapy with significant increase in hair density measured by digital
      dermoscopy. However, regression of these results was observed during the follow
      up period but was still significantly better than before treatment. There were
      statistically significant improvements in clinical score, global assessments,
      dermoscopic, and digital dermoscopic findings in both group IA and group IIA
      received carboxytherapy in comparison with group IB and group IIB received
      placebo injections, respectively. CONCLUSION: Carboxytherapy seems to be a
      promising therapeutic option for patchy AA and could be helpful as an adjuvant
      therapy of AGA but more than 6 sessions are required and adjuvants are
      recommended for maintenance of the results.

PMID- 29460510
TI  - Confocal multispot microscope for fast and deep imaging in semicleared tissues.
AB  - Although perfectly transparent specimens are imaged faster with light-sheet
      microscopy, less transparent samples are often imaged with two-photon microscopy
      leveraging its robustness to scattering; however, at the price of increased
      acquisition times. Clearing methods that are capable of rendering strongly
      scattering samples such as brain tissue perfectly transparent specimens are often
      complex, costly, and time intensive, even though for many applications a slightly
      lower level of tissue transparency is sufficient and easily achieved with simpler
      and faster methods. Here, we present a microscope type that has been geared
      toward the imaging of semicleared tissue by combining multispot two-photon
      excitation with rolling shutter wide-field detection to image deep and fast
      inside semicleared mouse brain. We present a theoretical and experimental
      evaluation of the point spread function and contrast as a function of shutter
      size. Finally, we demonstrate microscope performance in fixed brain slices by
      imaging dendritic spines up to 400-MUm deep.

PMID- 29460511
TI  - Tissue perfusion rate estimation with compression-based photoacoustic-ultrasound
      imaging (Erratum).
AB  - This erratum corrects errors with the figure citations in
      https://doi.org/10.1117/1.JBO.23.1.016010.

PMID- 29460512
TI  - Coverage of multiple recessions using the tunnel technique and a collagen matrix
      in the maxilla or mandible: a 6-month study.
AB  - Multiple recession defects in the dentition of the patients are routinely
      encountered in clinical practice and as such present a challenge for clinicians.
      Periodontal plastic surgical procedures aim to restore both esthetics as function
      in periodontal tissues. The objective of this study was to evaluate and compare
      the clinical efficacy of using a tunnel technique with a collagen matrix to cover
      multiple recessions in the maxilla or mandible. Fourteen patients were enrolled
      in the study. Patients in the maxilla-group and mandible-group were treated with
      xenogeneic collagen matrix using the tunnel technique. Clinical recordings were
      obtained at baseline and after 3 and 6 months. The percentage of average
      recession coverage (ARC), the percentage rate of patients with complete coverage
      of all recessions (CRC-1) and the percentage rate of complete coverage of
      recession defects (CRC-2) were evaluated after 3 and 6 months after the surgery.
      Statistically significant differences were observed in every parameter except
      probing depth between the baseline values compared to the values 3 and 6 months
      after the procedure in both groups. The mean ARC 6 months after the procedure was
      96.8% in the maxilla and 81.3% in the mandible. At 6 months after the procedure,
      a complete root coverage was obtained in 2 out of 9 patients and 31 out of 39
      recessions (79%) in the maxilla and 0 out of 5 patients and 10 out of 20
      recessions (50%) in the mandible. A collagen matrix combined with the tunnel
      technique led to a satisfactory ARC, CRC- 2 and resulted in an unsatisfactory CRC
      1.

PMID- 29460513
TI  - The effect of gingival wall location on the marginal seal of class ii
      restorations prepared with a flowable bulk-fill resin-based composite.
AB  - SureFil SDR is a flowable resin-based composite that allows a single incremental
      bulk placement. The marginal seal of SureFil SDR at the gingival margins of class
      II restorations located apical to the cemento-enamel-junction (CEJ) has not been
      adequately evaluated compared to those located occlusal to the CEJ. Forty class
      II cavities were prepared in human molars. The gingival margins of 20
      preparations were located 0.5 mm occlusal to the CEJ, and the other 20
      preparations were located 0.5 mm apical to the CEJ. The cavities surfaces were
      bonded with XenoV dental adhesive and filled with SDR in one bulk increment up to
      4 mm, after which they were covered with CeramX. The teeth were subjected to
      thermo-and load-cycling, and their gingival margins were exposed to 0.5% basic
      fuchsin solution. The specimens were sectioned mesio-distally and scored for
      microleakage. A Wilcoxon test for pairwise comparison was performed to determine
      significance. Dye penetration was observed in 30% of the 20 restorations with
      cavo-surface margins located occlusal to the CEJ and in 55% of the 20
      restorations with cavo-surface margins located apical to the CEJ. The bulk-fill
      flowable resin base SureFil SDR with XenoV dental adhesive provided a better
      marginal seal in class II restorations with gingival margins above the CEJ
      compared to restorations with gingival margins below the CEJ. SDR should not be
      recommended for class II cavity preparations with gingival margins located below
      the CEJ.

PMID- 29460514
TI  - Rehabilitations with immediate loading of one-piece implants stabilized with
      intraoral welding.
AB  - The authors present an implant prosthesis procedure that uses screws on one-piece
      implants connected with a titanium pin at their abutment level and one supporter
      titanium bar in order to guarantee immediate stabilization. These can be
      implanted and fitted with customized temporary crowns in a single surgical
      procedure, restoring function and aesthetics and consenting recovery of the bone
      deficit with reduced healing times and limited patient discomfort. One-piece wide
      diameter titanium screw implants with thread measurements of 2.1 and 2.6 mm
      (smaller diameter) up to diameter of 4.5 mm with one abutment of 2.0 and 2.5 mm
      respectively, were positioned and splinted by intraoral welding. One-piece
      titanium implants were used together with a pin (needle) titanium implant as
      supporting structure to achieve deep stabilization. The Scialom-like pin has a
      diameter of 1.2 mm and it is long enough to reach deep cortical bone that is
      ?bicorticalism?. The One-piece implant is tightly connected to the needle implant
      by means of Mondani intra-oral welding technique. In severely atrophic anterior
      maxilla, the use of this method allows the immediate loading of a fixed resin
      prosthesis soon after surgery. These implants yielded satisfactory functional and
      aesthetic outcome in bone-deficient upper anterior sectors, without invasive
      regenerative procedures. The low invasiveness of this approach also consents
      rapid healing, reduced biological burden and greater patient benefit.

PMID- 29460515
TI  - The importance of occlusal trauma in the primary etiology of periodontal disease.
AB  - The presence of periodontal disease can be ascertained by clinical examination
      (redness, edema and probe depth, bleeding-on-probing). Occlusal adjustment can
      lead to a marked, stable improvement in periodontal health in terms of bacterial
      profile and clinical appearance, presumably by obviating tissue distress caused
      by occlusal dysfunction, thereby providing unfavorable conditions for bacterial
      growth. Therefore, occlusal trauma can be an essential indicator of the
      periodontal disease and, if not corrected, could lead to a relapse.

PMID- 29460516
TI  - Clinical applications of Natural Bone Morphoproteins in dentistry: a narrative
      review.
AB  - The need to restore bone loss in maxilla and mandible has led to find natural
      bone substitutes, such as fresh autogenous bone grafts. Fresh autogenous bone
      grafts (FABGs) have a remarkable capacity to induce new bone formation, a
      phenomenon called ?osteoinduction.? FABGs are useful in craniomaxillofacial and
      oral applications to restore bone deficiencies. The isolation of those proteins
      believed to be responsible for the osteoinductive activity of FABGs, namely
      Natural Bone Morphogenetic Proteins (NBMPs), led to a new era in bone
      regeneration. NBMPs have been approved for use in specific oral and maxillofacial
      applications. Clinical trials and studies of oral and craniofacial surgery have
      indicated that NBMPs can promote bone repair. Information about the biology,
      chemistry, and actions of NBMPs has called into question whether NBMPs would
      result in clinically useful bone induction and morphogenesis. Preclinical and
      specific clinical trials have indicated the efficacy of NBMPs either combined
      with autograft or compared with an autograft alone. In light of questions about
      potency and safety of NBMPs, however, additional high-level evidence is needed
      for specific clinical indications and appropriate patient populations that would
      benefit from their use.

PMID- 29460517
TI  - Peri-implant test is a proposal of a new procedure to prevent peri-implantitis
      and forensic claims.
AB  - Implant dentistry has become one of the most successful techniques for oral
      rehabilitation over the last 20 years. The success rate of implant oral
      rehabilitation is above 80% while peri-implant disease (PID) is the most
      important complication of implant dentistry. The main cause of PID is considered
      bacterial leakage at the implant-abutment connection of a two-piece implant
      system. Prevention and control of bacterial leakage at the implant-abutment
      connection is mandatory for reducing inflammation process around implants neck
      and achieving bone stability. Since bacteria leakage at implant-abutment
      connection level is the main cause of PID, a microbiological test should be
      important to identify bacteria that cause PID. According with the conclusion of
      workshop of the European Federation on Periodontology, a test that detects the
      most frequent bacterial species involved in the onset of PID (Actinobacillus
      actinomycetecomitans, Porphyromonas gengivalis, Tannnerella forsythia, Treponema
      denticola) should be used in clinical practice. In fact, PID progression depends
      on the typology, quantity and composition of bacterial flora in peri-implant
      pockets, so controlling PID onset and progression, is a keystone for preventing
      implant failures and consequently forensic conflicts. The effort to prevent PID
      and consequently assurance or forensic conflicts have become one of the main
      focal points of all dental professionals. Behind these efforts lie, above all,
      ethical but also economic reasons, as well as a desire to prevent PID, improving
      implant care quality and increasing the legal security of health care
      professionals themselves. Since the legal decisions in our society influence how
      we practice dentistry, especially in the fast-evolving field of implant
      dentistry, using diagnostic tools that will allow dentists to demonstrate that
      they have acted correctly in accordance with the knowledge of modern medicine, it
      is of great importance to defend themselves in the case of legal-legal disputes.

PMID- 29460518
TI  - Prevalence of HIV-related oral manifestations and their association with HAART
      and CD4+ T cell count: a review.
AB  - HIV infection is one of the major health problem of the last decades. This
      disease causes a chronic infection that can lead to acquired immunodeficiency
      syndrome (AIDS). According to the Global AIDS update, released in 2016 by HIV
      department of World Health Organization (WHO) and by the Joint United Nations
      Program on HIV/AIDS (UNAIDS), at the end of 2015, 36.7 million people were
      infected by HIV: 34.9 million of these were adults and 1.8 million were children
      under 15 years of age. The same report shows that during 2015, 2.1 million of new
      infection cases have occurred all over the world and about 1.1 million people
      have died for HIV. The aim of this short review is to up-date of the main HIV
      related oral manifestations and their correlation with HAART (Highly Active
      Antiretroviral Therapy) and CD4+ T-cell count. Despite that more than 20 years
      have elapsed, this classification still remains valid: even today, group 1
      lesions are found in the majority of HIV-positive patients with oral
      manifestations. Group 1 includes the following conditions: oral candidiasis
      (pseudomembranous candidiasis, erythematous candidiasis, angle cheilitis), oral
      hairy leukoplakia, periodontal diseases (necrotizing gingivitis, necrotizing
      periodontitis, linear gingival erythema), Kaposi?s sarcoma, and non-Hodgkin?s
      lymphoma. Melanotic hyperpigmentation, HSV infection and HPV infection, which are
      included in group 2, are also common. Oral candidiasis, oral hairy leukoplakia,
      Kaposi?s sarcoma and HSV infection are the lesions that have seen the major drop
      in their incidence after the HAART introduction. The increase in CD4+ T-cell
      count is not significantly correlated to the decrease of every type of oral
      lesions, but it is statistically significant only in relation to oral candidiasis
      (p-value less than 0.001). Oral lesions are an important sign of immunodepression
      and with the introduction of HAART their incidence has strongly decreased,
      particularly in urban areas. Nevertheless, developing countries still have a high
      prevalence of these manifestations because of the persistence of many risk
      factors, like the difficulty to access treatment, poor oral hygiene, low
      socioeconomic status and late diagnosis.

PMID- 29460519
TI  - Human Papilloma Virus associated with oral cancer and preventive strategies: the
      role of vaccines.
AB  - The aim of this paper is to describe the efficacy of Human Papilloma Virus (HPV)
      vaccines for preventing oral cancer. A systematic review of the literature was
      conducted to describe the state of the art about HPV vaccines for preventing oral
      cancer. The aspects of prevention and control of infection by administering
      vaccines and the diffusion of sexual education campaigns are discussed also. In
      recent years there has been a growing interest in HPV in dentistry, suggesting a
      role of such a family of viruses in the development of oral cancers as well as of
      the uterine cervix. Even if the mass media have increasingly faced the problem,
      causing frequent alarming among patients, the dentist therefore needs a complete
      and up-to-date knowledge of this infectious condition that is one of the most
      common causes of sexually transmitted mucous membrane infections (eg genital,
      anal and oral). Recent studies about HPV infection are a basic requirement in
      order to promote the HPV vaccinations and patient?s health.

PMID- 29460520
TI  - Hypnotic approach during dental treatment: analysis of descriptive data of a case
      series.
AB  - Anxiety and worry are important components that affect the patient?s behaviour
      during dental sessions and influence the effectiveness of dental treatment.
      Psychological approach and hypnotic approach (HA) have in recent years assumed
      increasing prominence as effective treatment regimes. Dentists have used a number
      of methods in the management of dental phobic disorders through HA. However the
      efficacy of HA in controlling anxiety and worry is controversial. The aim of the
      present study is to describe the response of patient to HA during dental
      treatment. The study of the population consisted of 42 patients, these being 50%
      random sample of consecutive patients presenting to a private practise over an 8
      year period. In 38 patients HA was induced. 4 patients were not susceptible to
      HA. There were 20 women (52.6%) and 18 men (47.3%) with a mean age of 47.2 years
      (range 30-69 years). At the end of dental sessions with HA all the patients were
      asked to answer the following questions: 1) Have you been hypnotized in the past?
      2) Were you aware of dental applications of HA? 3) How do you evaluate the use of
      this technique in the field of dental care? 4) Do you think that you can use this
      procedure in the future too? The answers were as follows: question 1: 34 patients
      answered yes, 4 no; question 2: 34 answered yes, 4 no; question 3: the choice was
      between ?very useful?, ?useful?, ?Indifferent?, ?to avoid?. Twenty-nine patients
      indicated ?very useful?, and 9 ?useful?; question 4: the choice was between yes
      and no. All patients answered yes. This study adds further support to a growing
      body of evidence relating HA to a better compliance to dental treatment. The
      dental situation in particular lends itself to carefully controlled investigation
      providing further evidence to support a robust theory.

PMID- 29460521
TI  - HPV acting on E-cadherin, p53 and p16: literature review.
AB  - In addition to tobacco and alcohol consumption, the two main risk factors for
      oral squamous cell carcinoma (OSCC), recent studies have revealed infections with
      human papilloma virus (HPV) as an additional risk factor for OSCC development. In
      the field of head and neck malignancies, the prevalence of HPV infections in
      oropharyngeal cancer (OC) ranges in different studies up to 84%. While HPV
      infection is discussed as an independent risk factor in this region, its
      distinguished role in carcinogenesis of tumours localized to the oral cavity
      remains uncertain. A systematic literature search was performed using PubMed,
      Cochrane library, Science Direct, and the Internet search, with language
      restricted to English. The search included published studies which dealt with
      detection methods of HPV-related oral and oropharyngeal cancers and biomolecular
      studies, particularly regarding the compromising of p53 p16 and e-cadherin?s. P53
      Tumour suppressor protein p53 has several functions that are related to
      maintaining genomic stability and inhibiting cell proliferation in response to
      DNA damage. For preventing neoplasia to occur, the most important of these
      functions are cessation of cell growth and induction of either apoptosis or
      senescence. P16 is a cellular protein involved in cell cycle regulation. It is a
      cyclin-dependent kinase 4 (CDK4) inhibitor, and is integral to Rb mediated
      regulation of G1-S phase of the cell cycle. P16 is expressed at a very low level
      in normal cell as Rb inhibits transcription of p16. Various detection methods
      ranging from immunohistochemistry (IHC) to molecular techniques have been used to
      determine the HPV status of HNSCC. E-cadherin, a 120 kDa Type I classical
      cadherin, is expressed primarily on epithelial cells. It is found on the surface
      of keratinocytesand Langerhans cells (LC) and E-cadherin mediated adhesion
      between these cell types is required for LC retention in the epidermis. It is
      also an important tumour suppressor protein: its loss or inactivation is
      associated with epithelial-to-mesenchymal transition (EMT), a process involving
      dedifferentiation, infiltration and metastasis of tumours. Oral carcinogenesis is
      a multi-factorial process involving socioeconomic, environmental and microbial
      factors leading to multistep changes. Smoking and tobacco exposure seems to
      modify the survival and recurrence of HPV positive tumours and should be
      considered in future trials for risk stratification of HPV positive patients. HPV
      associated oropharynx cancer represents a distinct clinical and biologic entity
      with many unresolved issues that will be investigated in future translational,
      clinical research. We need to further explore and understand why the disease
      occurs predominantly in males, and whether the natural history of oral HPV
      infection differences in men and women.

PMID- 29460522
TI  - Mechanical, chemical and biological aspects of titanium and titanium alloys in
      implant dentistry.
AB  - Implant dentistry has become a popular restorative option in clinical practice.
      Titanium and titanium alloys are the gold standard for endo-osseus dental
      implants production, thanks to their biocompatibility, resistance to corrosion
      and mechanical properties. The characteristics of the titanium implant surface
      seem to be particularly relevant in the early phase of osseointegration.
      Furthermore, the microstructure of implant surface can largely influence the bone
      remodelling at the level of the bone-implant surface. Recently, research has
      stated on the long-term of both survival and success rates of osseointegrated
      implants and mainly on biomechanical aspects, such as load distribution and
      biochemical and histological processes at the bone-implant interface. This short
      review reports recent knowledge on chemical and mechanical properties, biological
      aspects, innovations in preventing peri-implantitis, describing clinical
      applications and recent improvements of titanium dental implants. In addition, it
      highlights current knowledge about a new implant coating that has been
      demonstrated to reduce the number of initially adhering bacteria and peri
      implantitis.

PMID- 29460523
TI  - Depression and distress in burning mouth syndrome: A case control study.
AB  - To compare the results of psychometric tests in patients with BMS and controls,
      participants were tested for depression, anxiety, fatigue and distress. Patients
      with BMS had noticeably higher scores for depression, fatigue and distress,
      compared to controls. Depression and distress were significantly correlated with
      the burning symptom. Moreover, distress and burning symptoms proved to be
      interdependent. Depression seems to play a specific role in BMS. Burning symptoms
      affect quality of life of patients and they could be a predictor of distress.

PMID- 29460524
TI  - Psychiatric disorders in oral lichen planus: a preliminary case control study.
AB  - The aim of this study was to evaluate the prevalence of psychiatric symptoms in
      patients with oral lichen planus (OLP) compared to a control group. Eleven
      patients (mean age 65.2 years-old), with diagnosis of OLP and 13 controls (mean
      age 64.8 years-old) underwent a psychiatric evaluation with five psychometric
      scales: Visual Analogue Scale (VAS), Hamilton Rating Scale for Depression (HAM
      D), State-Trait Anxiety Inventory (STAI 1-2), Distress Thermometer (DT) and Brief
      Fatigue Inventory (BFI). Seventy-three % of OLP group presented a VAS score of
      mild type; 9% had depressive symptoms; 100% of the sample had a score above the
      cut-off for state and trait anxiety; 45% presented Distress (36% moderate type).
      However, no statistical difference was found in comparison with the control
      group. In this study, there was no difference in these parameters between the OLP
      group and the control group. Perhaps, a larger cohort of patients could give
      different results.

PMID- 29460525
TI  - How social media meet patients? questions: YouTube? review for children oral
      thrush.
AB  - YouTube? is increasingly being used by patients to obtain health-related
      information. No studies have evaluated the content of YouTube? videos on children
      oral thrush. The aim of this work is to examine the quality of information
      offered by this platform about oral thrush in children. Searching term ?oral
      thrush in children? (OTC) displayed a total of 2.790 results. Of the top 60
      videos analyzed, 27 were excluded. The main source of upload was from generalist
      information YouTube(r) channels (GC) followed by healthcare professionals (HP),
      individual users (IU), and healthcare information channels (HC); usefulness of
      videos is successfully correlated with the number of visualization, number of
      likes and viewing rate and was interdependent with the number of visualizations,
      number of likes and VR. However, videos on the oral thrush do not have
      satisfactory quality information. HP themselves, along with HC, do not seem to
      provide more appropriate information on COT, than GC or IU.

PMID- 29460526
TI  - Analysis of saliva samples in patients with Prader-Willi syndrome.
AB  - Patients affected by Prader-Willi Syndrome (PWS) usually show orofacial
      dysfunction, poor oral hygiene, severe tooth wear, generalized caries and thick
      sticky saliva. The aim of this study was to evaluate molecular/ionic changings in
      PWS patients compared to controls, as well as unstimulated salivary flow rate
      (SFR); 7 patients with a mean age of 20.0+/-5.45 years were enrolled in the study
      group (PWS group) and 5 patients with a mean age of 22.6+/-3.05 years, in the
      control group. Results showed a greater Na+ (p=0.003), Cl+ (p=0.004) and P
      (p=0.001) concentration in saliva of PWS group as well as a greater concentration
      of secretory IgA (p=0.003) with a reduction of SFR (p=0.004) compared to
      controls. A Spearman?s analysis (based on the SFR of both groups) revealed an
      inverse correlation with Na (rho=-0.747), Cl (rho=-0.723), P (rho=-0.637) and
      sIgA (rho=-0.707) concentration and SFR, when linear regression model was
      performed only P and SFR were interdependent (beta=-0.748; p=0.005).

PMID- 29460527
TI  - Management of denture stomatitis: a narrative review.
AB  - Candida albicans is a typical commensal microorganism of the oral cavity that can
      become virulent in certain conditions and cause denture stomatitis (DS). Many
      conditions can predispose for DS, including local and systemic alterations. The
      therapeutical approach to DS is various and both topical and systemic
      alternatives can be considered. Azoles molecules are the most common used, both
      topically and systemically, but in recent years various alternatives have been
      proposed. This review aims to examine the scientific literature to evaluate the
      effectiveness of conventional therapies and the potential of the new ones.

PMID- 29460528
TI  - How social media meet patients? questions: YouTube? review for mouth sores in
      children.
AB  - Recurrent aphthous stomatitis (RAS) is one of the most common causes of mouth
      sores in children so the management of this condition is a matter of great
      importance. YouTube? is increasingly being used by patients to obtain health
      related information. The aim of this work is to examine the quality of
      information offered by YouTube? about mouth sores in children (MSC). Searching
      the term ?mouth sores in children?, (MSC) displayed 12.300 results. Of the top 60
      videos analyzed, 31 were excluded following exclusion criteria. The major source
      of upload was from healthcare information channels (HC-41,38%), followed by
      individual users (HP-25.59%), healthcare professionals (IU-17.24%) and generalist
      information channels (HC-13.78%); 20.69% of them deal with predisposing factors,
      and related pathologies, the majority of these propose home remedies (60.72%)
      rather than topical analgesic drugs (21.43%), antimicrobials (7.14%) and topical
      steroids (3.57). Most of the videos analyzed were slightly useful (68.97%).
      Information about mouth sores in children on YouTube? was poor regardless of the
      upload source. Analyzing health content on social platforms is a starting point
      for providing greater quality of health-related information.

PMID- 29460529
TI  - Systemic and topical photodynamic therapy (PDT) on oral mucosa lesions: an
      overview.
AB  - Photodynamic Therapy (PDT) is a minimally invasive treatment that has shown
      promising results in treating preneoplasticlesions. PDT reckons on the
      administration of a drug (photosensitizer), which can be used in a topical or
      systemic form. Photodynamic therapy has been successfully used in the management
      of a variety of pathologies from different anatomical sites, including the head,
      neck, brain and lungs, hepatobiliary tree and other gastrointestinal and
      urological pathologies, skin, gynaecological conditions and in vascular
      anomalies. Starting from these same considerations, PDT has also been adopted for
      oral malignant and premalignant lesions? treatment, and should be kept under
      investigation as a promising therapeutic management of leukoplakia and
      preneoplastic lesions of the oral cavity.

PMID- 29460530
TI  - Oral-facial-digital syndrome (OFD): 31-year follow-up management and monitoring.
AB  - Orofaciodigital syndrome (OFD) is a group of hereditary disorders identified by
      malformations of the mouth (oris), face (facies), hands and feet (digitus=finger
      and toe). Although there are several different types reported in the literature,
      there is a great overlap in their clinical presentation. The full spectrum of all
      disorders due to OFD is not yet fully understood, since each patient shows
      variations in the expression of the syndrome. In the oral cavity, teeth are often
      affected by various alterations, such as dental caries, abnormal teeth, enamel
      hypoplasia, supernumerary teeth and dental agenesis. Treatment of a syndromic
      patient with a complex picture showing conditions such as palatine fissures and a
      severe hypodontia involves a multidisciplinary approach and a careful periodical
      follow-up.

PMID- 29460531
TI  - Telescopic overdenture on natural teeth: prosthetic rehabilitation on (OFD)
      syndromic patient and a review on available literature.
AB  - Orofaciodigital syndromes (OFD) are rare genetical disorders characterized by
      malformations of the mouth (oris), face (facies), hands and feet (digitus =
      finger, toe). It is still impossible to fully understand the whole spectrum of
      all dysfunctions due to OFD, since the expressions of the syndrome vary in each
      patient. There are various alterations, thoroughly described in literature that
      can affect the oral cavity such as dental caries, abnormal teeth, enamel
      hypoplasia, supernumerary teeth and dental agenesis. A syndromic patient with a
      complex picture showing conditions such as palatine fissures and a severe
      hypodontia has to be treated using a multidisciplinary approach, and in
      particular, needs a prosthetic rehabilitation for the restoration of missing
      dental elements in the arch.

PMID- 29460532
TI  - Lichen planus: molecular pathway and clinical implications in oral disorders.
AB  - Stem cells play a role in many mucosal disorders characterised by abnormal
      proliferation and differentiation of keratinocytes, such as oral lichen planus
      (OLP). In OLP there were changes in stem cell markers as component of integrin
      complexes alpha6 and beta1 integrin increased along with increase of melanoma
      associated chondroitin sulphate proteoglycan (MCSP) and decreased of notch1 (N1)
      and keratin 15 (K15). Stem cell marker expression may be altered by pathological
      signalling in these lesions. Cadherins are transmembrane receptors that provide
      cell-cell contact and communication function through calcium-dependent homophilic
      and heterophilic interactions. In actively diseased areas of OLP lesions, basal
      keratinocytes downregulate CD40 and were focally E-cadherin-negative, in contrast
      to non-diseased areas and normal oral mucosa. This loss of E-cadherin expression
      may contribute to epithelial basal cell destruction and T-cell migration into the
      epithelial compartment in OLP. In addition, Growth factor pathways as a role in
      OLP and has been analyzed in this review.

PMID- 29460533
TI  - Colonization of Legionella spp. In dental unit waterlines.
AB  - Legionella spp. are ubiquitous in aquatic habitats and water distribution
      systems, including dental unit waterlines. Surveys have shown that the percentage
      of samples taken at different dental sites that were positive for Legionella spp.
      were highly variable and ranged from 0% to 100%. Cultivation is the principal
      approach to evaluating bacterial contamination employed in the past, but applying
      this approach to testing for Legionella spp. may result in false-negative data or
      underestimated bacterial counts. PCR and direct fluorescent counts can detect
      viable non-cultivable bacteria, which are not counted by plating procedures.
      Legionella spp., commonly form such viable non-culturable cells and it is likely
      that they contribute to the difference between plate count results and those of
      PCR and fluorescent-antibody detection. However, studies have shown that
      Legionella is present in the municipal water source in spite of the current
      filtration and chlorination procedures. Once Legionella reaches the building
      water system, it settles down into a biofilm layer of stagnant water. By means of
      this layer, Legionella can protect itself from antimicrobial agents and then
      multiply. Dental unit waterlines may be contaminated with opportunistic bacteria.
      The water quality in the dental units should be controlled to eliminate
      opportunistic pathogens and to provide water for dental treatment that meets
      public health standards for potable water.

PMID- 29460534
TI  - Focus on periodontal disease and development of endocarditis.
AB  - : Infective endocarditis is a devastating disease with high morbidity and
      mortality. The link to oral bacteria has been known for many decades and has
      caused ongoing concern for dentists, patients and cardiologists. The microbiota
      of the mouth is extremely diverse and more than 700 bacterial species have been
      detected. Half of them are uncultivable so far. Oral microbiota is not uniform,
      specific sites exist in the mouth such as tongue, palate, cheek, teeth and
      periodontal pockets that have their own microbiota. Factors involved in the
      development of a bacterial endocarditis are difficult to define but a vulnerable
      surface (i.e. a damaged endocardium) and a high bacterial load in the blood seems
      to be decisive. The cause of microorganisms, in 90% of cases, are staphylococcus,
      streptococcus and enterococcus. Oral streptococci belong to viridans group
      (streptococcus mutans and streptococcus sanguis). As they are part of dental
      plaque, they could enter the bloodstream causing bacteraemia through daily habits
      like chewing or tooth brushing. Effective treatment of periodontal infections is
      important to reduce local inflammation and bacteraemia. In addition, poor
      periodontal health appears to increase the risk of cardiovascular disease,
      pulmonary disease, and preterm and low birth weight. CONCLUSIONS: Long-standing
      oral disease prevention protocols reduce the risk of developing periodontal
      disease. Data suggests that methods used to prevent cases of IE that originate
      from oral bacteria should focus on improving oral hygiene and reducing or
      eliminating gingivitis, which should reduce the incidence of bacteraemia after
      tooth-brushing and the need to extract teeth owing to periodontal disease and
      caries.

PMID- 29460535
TI  - Analyze my face.
AB  - Plastic surgery is gaining more and more popularity, while stigma and popular
      myths about it are gradually decreasing. Analyze My Face conjunctly deals with
      the two main problems of facial plastic surgery: the excessive rate of
      dissatisfaction, which results in high revision requests and negative
      psychological side-effects and the ?diagnosis by procedure? approach, which leads
      to erroneous measurements. This new and innovative method of Digital Facial
      Analysis is a direct non-expensive online service that provides professional and
      documented in-depth consultation to patients before they decide to undergo any
      type of facial intervention. The paper thoroughly explains the scientific method
      with which professionals provide customers with a facial assessment based on
      specific parameters which will be discussed (height, width, proportions,
      direction of facial growth, the way they assess each facial area in detail (eyes,
      mouth, cartilage), and the motivations for which they suggest to correct eventual
      defects through precise measurements, indicators and suggested interventions.
      Long-term evaluation of stability of surgical results and patient satisfaction
      achieved with digital facial analysis has not yet been established and needs
      further research. However, it is important to underline that the AMF approach
      tends to consider exclusively possible and feasible procedures that do not
      compromise functionality and that do not put patients in danger of serious
      damage. Problems or deformities that cannot be treated are always indicated. AMF
      aims to maximize professionality by giving practitioners an additional tool to
      aid their work, give unbiased opinions and look at the overall picture. It also
      aims to help patients by soothing their way into the complicated world of
      aesthetic surgery.

PMID- 29460536
TI  - Traumatic and surgical scars: successful treatment with a 1,565nm erbium-glass
      NAFL combined with IPL.
AB  - Scars are a very common condition of the general population and can have a
      profound impact on the psyche of the patient such as low self-esteem and feelings
      of psychosocial isolation. Various therapeutic approaches have been proposed for
      improving the clinical appearance of scars. Fractional mode of ablative and non
      ablative lasers has become a novel strategy for the treatment of scars. A total
      of 43 patients (Fitzpatrick skin type II to IV), clinically diagnosed of surgical
      and post-traumatic scars from January 2015 to December 2016, were treated. Each
      treatment comprised of several passes over the scars with different devices,
      using a 1.565nm scanned erbium-doped fiber NAFL and an IPL. All patients noted
      subjective improvement in cosmesis and functionality after treatment, also with a
      decreased pain and an increased mobility on the underlying plans. Numerous
      therapeutic strategies for traumatic and surgical scars have been suggested to
      date, but no consistent treatment modality has been established yet. In our
      study, we have shown that there was a significant collagen remodelling with
      decrease of scar vascularity and significant improvement of pliability of scar
      after combined treatment with non-ablative fractional resurfacing and IPL
      resulting in a remarkable improvement in scar vascularity, pigmentation and
      height.

PMID- 29460537
TI  - Pre-treatment with berberine enhances effect of 5-fluorouracil and cisplatin in
      HEP2 laryngeal cancer cell line.
AB  - Larynx squamous cell carcinoma represents one of the most common head and neck
      cancers in the world. Herbal drugs are popularly emerging as complementary and
      alternative therapies in cancer because of their cost effectiveness and minimal
      side effects. The present study was undertaken to explore the anti-tumor
      potential of berberine, an isoquinolone present in the extract of Tinospora
      cordifolia in HEP2 human laryngeal cancer cell line. Besides, it was aimed to
      investigate whether berberine could enhance the anti-cancer effect of 5
      fluorouracil and cisplatin in HEP2. Our data seem to support a role for berberine
      in decreasing the expression of genes usually seen overexpressed in larynx
      squamous cell carcinoma and involved in pathways such as those of cell cycle and
      regulation, differentiation, and epithelial-mesenchymal transition. Moreover, a
      down regulation of these genes caused by cisplatin or 5-fluorouracil, treatment
      of election in laryngeal cancers was enhanced by a 4h pre-treatment with
      berberine.

PMID- 29460539
TI  - Human polyomavirus in tonsillar microbiota of an Afghan population group.
AB  - Some studies have evidenced the role of human polyomaviruses in head and neck
      squamous cell carcinoma. BK, JC and SV40 human polyoma viruses are widely
      recognized as etiological agents associated with malignancies. The aim of this
      study was to analyse the prevalence of BK, IC and SV40 in tonsillar microbiota in
      a group of Afghan volunteers. A sample of the tonsillar microbiota was taken from
      a single site using a sterile oral swab paper stick. A fixed volume of purified
      DNA from each sample was tested by quantitative real-time polymerase chain
      reactions to evaluate the number of human cells and the number of viral genomes
      in each sample. The cell number was evaluated via the quantification of a single
      copy genomic sequence, which is located in the HMBS locus. The median analyzed
      cell number in each reaction was 4343 (interquartile range 2074-8470). SV40 was
      never detected, while prevalence rate was 0.11 (C.I. 0.06-0.20) for BK and 0.10
      (C.I. 0.05-0.19) for JC. Further studies are necessary to clarify whether
      polyomaviruses can be considered a risk factor of oral, oropharyngeal and
      laryngeal malignancies.

PMID- 29460538
TI  - Detection of endocarditis bacteria in tonsillar mucosa of Afghan population.
AB  - Endocarditis is a cardiovascular disease caused by the inflammation of the inner
      tissues of the heart, the endocardium, usually of the valves. Bacteraemia is
      essential in the development of endocarditis, and there are some findings that
      the main pathogens of endocarditis are viridans group streptococci: Streptococcus
      oralis, Streptococcus sanguinis, and Enterococcus faecalis. There is strong
      evidence that endocarditis bacteria are present in the tonsillar microbiota, so
      that tonsillar infection is associated with an increased risk of endocarditis.
      The aim of this manuscript is to investigate the presence of the main pathogens
      of endocarditis in tonsillar microbiota of an Afghan population group. A sample
      of 80 tonsil swabs were analyzed by quantitative real time PCR to detect
      endocarditis pathogens and an estimation of the total bacterial load. The median
      bacterial load in PCR reaction was 1.4x106 (interquartile range 4,7x105 -
      2,9x106). Three species, S. Oralis, S. Sanguinis, and E. Faecalis were found in
      large amounts in all specimens. On the other hand, S. Mitis was never detected.
      The S. Aureus was found in 3 samples with a prevalence of 0.04 (C.I. 0.01-0.10).
      The S. Mutans was found in 33 samples with a prevalence of 0.41 (C.I. 0.31-0.52).
      Endocarditis bacteria has been found into the tonsillar microbiota, so there is
      sufficient evidence to justify that the oral cavity is a reservoir of
      endocarditis bacteria that can have a significant impact on the cardiovascular
      function.

PMID- 29460540
TI  - Human papilloma virus in the tonsillar microbiota of an Afghan population group.
AB  - Cancer of the oral cavity is known to have a diverse aetiology that includes
      infectious agents. Human papilloma virus has been found to be associated with
      several types of human cancer, inclusive of cervical, vulvar, vaginal, penile,
      anal, and cancer of tonsil. The aim of this manuscript is to investigate the
      presence of human papilloma virus in tonsillar microbiota of an Afghan population
      group. A sample of the tonsillar microbiota was collected by oral swab paper
      stick from 80 healthy donors. The sample was investigated for the presence of
      high-risk human papillomavirus types 16, 18, 31 and 45 by real time PCR. Eight
      samples produced some positive endpoint signals for human papillomaviruses. The
      human papillomavirus 31 was the unique papillomavirus detected; its calculated
      prevalence rate was 0.10 (C.I. 0.05-0.19). However, the viral load was always
      very low, in the order of 10-3 viral genomes per cell. The high prevalence of
      high-risk human papillomavirus in healthy population suggest a need for further
      investigation on virus spreading and supports the development of vaccination
      strategies.

PMID- 29460541
TI  - Radiosurgery-assisted gingival displacement: a proof of concept technique to
      enhance the efficiency of intraoral digital impression.
AB  - Nowadays, an increasing number of dentists are using intraoral scanners (IOS) in
      their daily practice as an alternative to conventional impression taking. One of
      the main concerns is related to the capability of scanning the subgingival
      anatomy of the die, usually very challenging due to the limited operative field
      and the presence of oral fluids. The radiosurgery assisted gingival displacement
      technique (RAGD) may enhance the intraoral optical scanning of the finish line
      and neighbor tooth anatomy. The contour of the interim prosthesis is used to
      drive the tip of radiosurgery electrode along the tooth surface and open
      selectively the gingival crevice with a prosthetically-driven and minimally
      invasive approach. The clinical implication of this technique is related to
      increasing the efficiency and accuracy of the digital impression technique in the
      critical zone of the prosthetic shoulder.

PMID- 29460542
TI  - Temporomandibular joint and related structures: anatomical and Histological
      aspects.
AB  - In literature, there is no unanimous agreement about the anatomical and
      functional characteristics of the temporomandibular joint (TMJ) and its
      components. The aim of this work is to increase the knowledge about components of
      the temporomandibular joint, starting from the revision of classical anatomy,
      through macroscopic and microscopic study, 20 samples of human dissected
      temporomandibular joints.

PMID- 29460543
TI  - Anatomic relationship between temporomandibular joint and middle ear.
AB  - The present study was designed to identify a relationship between
      temporomandibular joint and tympanic cavity and potentially justify the possible
      clinical correlations between these two anatomical entities. For this reason the
      authors conducted an anatomic-pathological study about the temporomandibular
      joint (TMJ) and the neighboring anatomical areas of the middle ear by autopsy
      finds of human adults.

PMID- 29460544
TI  - TMJ?s capsule histological and macroscopical study: relationship between
      ligamentous laxity and TMI dysfunctions.
AB  - In this study, the authors examined the capsular structures of 20 human
      temporomandibular joints (TMJ) macroscopically and microscopically, in order to
      improve knowledge of these structures, as part of their possible participation in
      the genesis of TMJ dysfunctions.

PMID- 29460545
TI  - Hyperbaric oxygen therapy (HBOT) and peridontal health.
AB  - This study has tested the effects of hyperbaric oxygen in periodontal structures
      in agreement with the theories supported by literature research. Eight patients,
      from 30 to 50 years-of-age, were tested with pure oxygen inhalation, at the 2.5
      ATA absolute pressure. Main approved tests of periodontal health were evaluated
      before and after HBOT?s cycles. The results in all patients treated with HBOT,
      have founded clear improvement of clinical and instrumental parameters.

PMID- 29460546
TI  - FDPS finish line design and tooth preparation technique.
AB  - The purpose of this research is to perform and verify the ?modified 50 degrees 
      preparation? suggested by the authors. This procedure was performed with a
      scrupulous standardization of the tooth?s preparation and then of the laboratory
      techniques to produce a metal-ceramic crown, and the same for the crown
      cementation technique of on the preparation of the original sample. After the
      esthetic evaluations, the obtained sample was included in EPON resin and
      sectioned in the lingual-vestibular sense. The sections were then observed with
      an optical microscope in different magnifications for the final evaluations. The
      geometric design proposed presents the advantages of two great preparation
      techniques: 50 degrees  preparation and circumferential shoulder. The 50 degrees 
      bevel designed in first phase of preparation and the second phase of the
      circumferential 27 degrees  shoulder, together allowed to satisfy the following
      requirements: aesthetic, marginal accuracy, periodontal compliance, conservation
      and stability. However, this type of prosthetic preparation is not the only one,
      but it is one of the marginal designs in prosthetic dentistry.

PMID- 29460547
TI  - Zinc plus octenidine: a new formulation for treating periodontal pathogens. A
      single blind study.
AB  - Periodontal treatment has the aim to reduce oral infection, and prevent the
      progression of the disease. The potential benefits of new chemical devices for
      periodontal therapy, include improved patient compliance, an easier access to
      periodontal pocket and a lower dosage of antimicrobial agent. The objective of
      this study was to explore the efficacy of a chemical device containing zinc and
      octenidine in the treatment of chronic periodontitis in adult patients. Ten
      patients with a diagnosis of chronic periodontitis (20 localized chronic
      periodontitis sites) in the age group of 35 to 55 were selected. None of these
      patients received any surgical or non-surgical periodontal therapy and
      demonstrated radiographic evidence of moderate bone loss. The chemical device
      zinc plus octenedine was used by each patient after daily oral hygiene. Microbial
      analysis were analyzed at baseline and on the 15th day. After the treatment, a
      remarkable decrease in bacteria amount, both for some species and for the total
      count was observed in the study group. Specifically T. Forsythia and T. Denticola
      were eradicated whereas Total Bacteria Loading and Fusobacterium Nucleatum showed
      a reduction of 38&#x0025; and 55&#x0025;, respectively. Our study demonstrated
      the efficacy of the new chemical device containing zinc and octenidine in a
      sustained release drug delivery system in the management of moderate to severe
      chronic periodontitis.

PMID- 29460548
TI  - The role of zinc plus octenidine in the regulation of gene expression: an in
      vitro study.
AB  - Zinc was known in ancient times, and is diffused in the environment. The
      potential benefits offered by zinc supplementary therapy have been demonstrated
      in numerous clinical trials using oral or topical zinc products. The benefit of
      zinc can be in principle increased through association with other actives. The
      aim of this study is to evaluate the effect on primary human gingival fibroblast
      cell of a new formulation containing zinc and octenidine cations. Human gingival
      fibroblast cells were obtained from three healthy patients (14-year-old man, 15
      year-old woman and 20-year-old man) during extraction of teeth. The gene
      expression of 14 genes (ELANE, FN1, FBN, ITGA1, HAS1, ELN, DSP, ITGB1,
      HYAL1,TGFB1, TGFB2, TGFB3, TGFBR1 and TGFBR2) was investigated in HGF cell
      culture treated with 80MUm of Octenidine, 1000MUm of Zinc, 80MUm Octenidine +
      Zinc solution and the medium alone at 30 min. Prestoblue? data showed that as the
      active concentration increases (Octenidine, Zinc and Octenidine + Zinc) the
      percentage of cell vitality compared to that of untreated cells decrease. In this
      study, no statistically significant gene expression was observed between cells,
      treated with difference substances, and control cells. Our results points out
      that zinc plus octenidine shows a positive potential in periodontal disease
      treatment.

PMID- 29460549
TI  - IgM and IgA enriched polyclonal immunoglobulins reduce short term mortality in
      extremely low birth weight infants (ELBW) with sepsis: a retrospective cohort
      study.
AB  - BACKGROUND: Immunoglobulin supplementation is a debated strategy in fighting
      sepsis. We evaluated a polyclonal IgM and IgA enriched immunoglobulin (IgMeIVIG)
      preparation in reducing the short term mortality in extremely low birth weight
      neonates (ELBW) with proven infection. METHODS: ELBW infants born from January
      2008 to December 2014 were eligible for this retrospective casecontrol analysis
      if they were symptomatic and had a positive blood culture after 72hours of life.
      Patients received antibiotic treatment with or without IgMeIVIG
      (intravenously,250mg/kg/day for 3 days) within the 24 hours from clinical
      suspicion as per indication of the attending physician. Shortterm (7 and 21 days)
      mortality was the study primary outcome while secondary outcomes were: mortality
      at discharge, intraventricular hemorrhage, necrotizing enterocolitis,
      bronchopulmonary dysplasia, periventricular leukomalacia, and retinopathy of
      prematurity. RESULTS: Each group was composed by thirtynine infants. Both groups
      were similar for antenatal steroids, mode of delivery, birth weight, gestational
      age and SNAPII score as indicator of disease severity. Infants receiving IgMeIVIG
      had a significantly lower shortterm mortality compared with neonates receiving
      antibiotics alone: 6/39 (15%) vs 14/39 (36%); p = 0.038. No differences in other
      outcomes were found. CONCLUSIONS: This study shows that IgMeIVIG may have a role
      as adjuvant therapy in ELBW infants with proven sepsis. We warrant future
      prospective, blinded RCT studies where IgMeIVIG can be consistently used if
      needed throughout the NICU admission in ELBW septic neonates to appropriately
      evaluate its effect on mortality at discharge.

PMID- 29460550
TI  - Prevalence of overweight and obesity among Kuwaiti adolescents and associations
      with socioeconomic indicators: the study of health and activity among adolescents
      in Kuwait.
AB  - BACKGROUND: Kuwait is one of the Arab countries with the highest prevalence of
      overweight or obesity. However, few studies have described the prevalence of
      obesity in this country. AIM: To describe the prevalence of overweight and
      obesity among Kuwaiti adolescents; and to examine the association of overweight
      and obesity status with familial socioeconomic status (SES). METHODS: Cross
      sectional data from 591 adolescent students (47% boys, median age: 16 years) from
      the Study of Health and Activity among Adolescents in Kuwait in 2012 and 2013.
      Body weight status was determined using the International Obesity Task Force
      (IOTF) body mass index standards. SES was based on parental education. Odds ratio
      for overweight and obesity were calculated using multiple logistic regression.
      RESULTS: In our study, over half of the adolescents were overweight or obese
      54.3% (95% CI: 49.9-58.4). The prevalence of overweight (including obesity) was
      higher in boys (59.8%, 54.3- 66.3) than girls (49.2%, 43.5-54.8). No association
      between parental education and the risk of overweight/obesity was found.
      CONCLUSIONS: There is an alarmingly high rate of overweight/obesity among Kuwaiti
      adolescents, but we did not find evidence of a social gradient in obesity risk.
      Urgent actions are needed to reverse this epidemic across all social groups.

PMID- 29460551
TI  - Psychopathological risk in a sample of immigrant preadolescents in Italy.
AB  - BACKGROUND: Aim of the study is to collect information about emotional features
      in a sample of immigrant preadolescents in order to identify traits of emotional
      fragility or psychopathological risk factors. METHODS: The sample consists of
      1206 preadolescents (180 immigrants, 1026 Italian natives) attending the third
      year of the middle schools. In order to assess anxiety levels and the presence of
      depressive symptoms the Self- Administered Psychiatric Scale (SAFA-A) and the
      Children's Depression Inventory (CDI) were administered. Coping strategies and
      behavior problems were evaluated by the Coping Inventory for Stressful Situation
      (CISS) and the Youth Self Report scale (YRS). All teachers filled out the
      Teacher's Report Form (TRF). Parents were asked to fill out a form on social
      demographic features and the Multidimensional Scale of Perceived Social Support
      (MSPSS). RESULTS: Immigration resulted a risk factor for development of anxiety
      (OR=0,702), depression (OR=0,644), internalizing problems (OR=0,685), behavior
      problems (OR=0,622) and total problems (OR=0,719). Teachers observed more
      behavior problems and lower competences in immigrants than natives. Immigrants
      relied significantly more often on emotion-oriented coping strategies to resolve
      stressful situation than natives (p=0,045). Analyzing the immigrants sample,
      second generation children reported significantly higher levels in total
      competence (school, activity and relationship) than first generation ones
      (p=<00,1); on the contrary there were no significant differences between the two
      groups concerning other behavioral and emotional problems or the preferred coping
      style. Natives' families reported significantly higher levels of perceived
      support than immigrant ones. CONCLUSIONS: Our findings confirms the hypothesis
      that preadolescent immigrants are more at risk for psychopathological risk
      factors than native peers.

PMID- 29460552
TI  - Sudden Infant Death Syndrome (SIDS): the role of multidisciplinary teams
      experience of the SIDS-ALTE Center of Regione Liguria.
AB  - Aim of this paper is to highlight the importance of a multidisciplinary and
      multiprofessional management of SIDS for a complete approach to this tragic
      event. Both biomedical and psychosocial aspects are evaluated, focusing on the
      impact of SIDS diagnosis on the family. The paper describes the organization of
      our team, composed of a network of specialists involved in both prevention and
      management of SIDS. A protocol is proposed to improve SIDS diagnosis and
      management. In our team, the clinical pediatrician is the coordinator of
      specialists and the mediator between the family and the other specialists, thanks
      to his direct relationship with parents.

PMID- 29460553
TI  - Can early physical therapy positively affect the onset of independent walking in
      infants with Down syndrome? A retrospective cohort study.
AB  - BACKGROUND: The development of both gross and fine motor skills in a child with
      Down syndrome is generally delayed. The most seriously affected stage is the
      achievement of independent walking ability, which influences the onset of all
      following motor and cognityive skills. The study objectives were (a) to assess
      the time taken to achieve independent walking ability in a cohort of children
      with Down syndrome, (b) to examine differences in walking onset by patient
      characteristics, (c) to verify the effect of early physical therapy
      (Neurodevelopmental Treatment on the basis of Bobath Concept practised within the
      first months of life) in the achievement of that skill. METHODS: A retrospective
      study was carried out on a cohort of 86 children with Down Syndrome. The
      knowledge of the exact age of walking onset and information about comorobities
      and rehabilitation practised since birth were the eligibility criteria. RESULTS:
      The average age at which walking began in the sample was 26 months (Standard
      Deviation = 9.66). Some patient characteristics proved to be related negatively
      to the walking onset: gender male, trisomy 21, improved joint ligamentous laxity.
      When practised, early physical therapy was able to contrast the delay in walking.
      CONCLUSIONS: NDT-Bobath is a well-known and valid instrument for a child with
      Down syndrome to attain his highest possible psychomotor functioning level. This
      study pointed out for the first time ever its capability to contrast the delay on
      walking onset, which can influences positively the development of the following
      motor and cognitive skills.

PMID- 29460554
TI  - Cirp expression and therapeutic hypothermia for neonatal hypoxic-ischemic
      encephalopathy (HIE): a factor to consider when selecting depth and duration of
      cooling?

PMID- 29460555
TI  - [Editorial.Reflect on the past to project us to the future].

PMID- 29460556
TI  - [Clinical training and perception of its effects on the first novice nurse work
      experience: a phenomenological study].
AB  - AIM: The aim of this study was investigating, analysing and evaluating which
      aspects of the clinical training would be most useful to newly degreed nurses in
      carrying out their work activities post-graduation, based on their experience.
      METHODS:  This is a phenomenological qualitative study, with semi-structured,
      face-to-face, in depth interviews. We used purposive sample. Recruiting of
      interviewees stopped at achievement of data saturation. Interviews were all audio
      recorded and transcribed verbatim and analysed in double blind, in order to
      identify the main themes that emerged. The Van Kaam method was used to analyse
      interview content. RESULTS: Fourteen nurses, just graduated from Milan
      University, were involved in the study. Five themes emerged: the relation between
      theory-practice and the development of clinical thinking, the "time factor" in
      clinical training duration, the clinical nurse teacher as a professional model,
      the first days as a nurse: beautiful, traumatic and with loads of responsibility,
      and finally improvement strategies for a continuously evolving profession.
      CONCLUSION: Clinical training is confirmed as a key moment in the link of theory
      with practice and to infuse the newly qualified professional with the necessary
      autonomy, self-confidence and practical knowledge. Novice nurses highlighted many
      positive aspects of their training obtained by means of the clinical training
      experience, but also that they need time in order to develop confidence and learn
      to handle responsibility; in this respect, the clinical nurse teacher is seen as
      a fundamental figure.

PMID- 29460557
TI  - [Errors in Medicine: perceptions of nursing students in Rome].
AB  - INTRODUCTION: The error in medicine has long been discussed in scientific
      debates. The purpose of this study is to evaluate the degree knowledge, attitude
      and behavior of students in Nursing for the failure in the health sector.
      METHODS: It was administered to 231 students of Nursing of the Sapienza
      University of Rome (171 females and 60 males), aged between 21 and 45 years, a
      structured questionnaire in three questions that explore the experiences and
      opinions about the errors found in medical practice, the causes underlying them
      and the mistakes that should never be committed. Data were collected, stratified
      by sex, age, marital status, and analyzed using the chi2 test. Significance was
      set at p<=0.05. RESULTS: The 5 errors found more frequently in clinical practice
      by the students were the following: Errors that favors the onset of hospital
      infections (58.9%); Non adherence to protocols (50.2%); Patient care (45.9%);
      Errors due to the administration of therapies and drugs (45.9%); Errors relating
      to the execution of withdrawals (35.9%). The five cases considered most
      frequently responsible for such errors were: the rush (70.1%), followed by
      neglect / superficial (55%); disorganization (51.5%); not hygienically /
      infertility (50.6%) and inattention (42.9%). With regard to the errors that you
      should never commit, students have shown more frequently: the errors of
      administration of therapies / medications (69.3%); errors of prescription
      therapies / medications (58.9%); errors related to surgery (52.8%); the exchange
      of patient or misidentification of the patient (50.6%); errors that favor the
      occurrence of hospital infections (48.1%). CONCLUSIONS: The results of this study
      shows the importance of a culture of error in medicine, also as part of
      undergraduate education, in order to train and educate future health
      professionals to this issue in order to promoting patient safety and quality of
      health.

PMID- 29460558
TI  - [The impact of Reiki on side effects in patients with head-neck neoplasia
      undergoing radiotherapy: a pilot study].
AB  - BACKGROUND: Cancer patients often report symptoms related to therapeutic
      treatment, whose management is based on traditional medicine. In recent years,
      however, there has been growing interest towards adopting some form of
      complementary medicine, among these, Reiki. The aim of this study is to evaluate
      how this type of discipline can contribute to managing radiotherapy-related
      symptoms in patients with head and neck cancer. METHOD: The study was performed
      in the Radiotherapy Department at the Regina Elena National Cancer Institute in
      Rome. To assess QoL, the FACT-H N questionnaire was used, while the CTCAE Scale
      was adopted to evaluate mucositis, cutaneous toxicity and salivation. RESULTS:
      10.5% of patients were reported to experience strong pain in the fifth week,
      compared to 21.1% of patients in the previous week; a degree of mucositis equal
      to G3 was also found in 15.5% of cases according to the clinical evaluation, as
      well as in 10.5% of patients according to the functional one. Only one case
      (5.3%) of grade 3 cutaneous toxicity was registered. CONCLUSION: The study shows
      how the Reiki treatment benefits patients in most cases, with both psychological
      support to help deal with the therapeutic process together with integrated
      support towards pain therapy.

PMID- 29460559
TI  - [How the bed rest period and the posture assumed by the patient post lumbar
      puncture caninfluence the onset of complications: a rapid evidence assessment].
AB  - AIM: To identify how the bed rest period and the posture assumed by the patient
      after lumbar puncture can influence the onset of complications, and which nursing
      interventions to adopt in order to reduce the complications. METHOD: A rapid
      assessment review was performed and the electronic databases PubMed, CINAHL, and
      the Cochrane Central Register of Controlled Trials were searched between 2001 and
      2015. RESULTS: Initially, 407 studies were retrieved, and 5 of these publications
      were considered to be eligible for the purpose of the study,4 comparing different
      periods of bed rest and 1 comparing patients position. Headache, nausea, vomiting
      and other symptoms, do not seem to reduce with a 24 hours longer bed rest. There
      is a lack of evidence on the effectiveness of early mobilization, as well as on
      the effects of different postures after the procedure performed to reduce the
      incidence of complications. Only a statistically significant gender difference in
      the onset of the headache was found: women seem to be more at risk. The selected
      studies showed a medium-low methodological quality and a high heterogeneity in
      the systems used to measure the symptoms, in the features and dimensions of the
      investigated populations. CONCLUSIONS: Currently available data do not permit to
      identify care interventions related to effective bed rest period based on
      scientific evidences in order to prevent post rachicentesis complications. It is
      therefore considered necessary to conduct further experimental and observational
      studies, with a high methodological rigor in order to maximize the effectiveness
      of nursing care.

PMID- 29460560
TI  - [Isolation precautions in multi drug resistent infections and nursing workload in
      a general intensive care unit].
AB  - BACKGROUND: Critically ill patients in ICU are exposed to high risk of hospital
      acquired infections. In recent years, the multi drug resistant microorganisms
      (MDR) represent the most worrying epidemiological problem. AIM: The aim of this
      study is to evaluate the relationship between isolation precautions and nursing
      workload. METHODS: We studied patients who had an infection by MDR, subject to
      isolation precautions, and measured their NAS score during stay in ICU. MDR
      infections of studied patients were: Acinetobacter Baumannii, Klebsiella KPC,
      MRSA, Pseudomonas, Escherichia coli, Serratia marcescens e Clostridium difficile.
      Isolation precutions wer identified by color code (green, yellow, red). RESULTS:
      We studied 44 patients during the year 2012. NAS average was 81.54 +/- 10.25. NAS
      average for "green code" patients was 81.25 +/- 22.12, for "yellow code" patients
      was 82.57 +/- 11.25 and for "red code" patients was 79.06 +/- 29.12. DISCUSSION:
      the presence of isolation precautions seems to have no influence on nursing
      workload measured by NAS score, except for Acinetobacter Baumannii infection.
      Further research will be needed for better evaluation of this topic.

PMID- 29460561
TI  - Modified Moral Distress Scale (MDS-11): Validation Study Among Italian Nurses.
AB  - BACKGROUND: Moral distress (MD) has significant implications on individual and
      organizational health. However there is a lack of an instrument to assess it
      among Italian nurses. AIM: The main aim of this study was to validate a brief
      instrument to assess MD, developed from the Corley's Moral Distress Scale (MDS).
      METHOD: The modified MDS scale was subjected to content and cultural validity.
      The scale was administered to 347 nurses. Psychometric analysis were performed to
      assess construct validity. RESULTS: The scale consists of 11 items, investigating
      MD in nursing practice in different clinical settings. The dimensionality of the
      scale was investigated through exploratory factor analysis (EFA), which showed a
      two-dimensional structure labeled futility and potential damage. The futility
      refers to feelings of powerlessness and ineffectiveness in some clinical
      situations; the potential damage dimension captures feelings of powerlessness
      when nurses are forced to tolerate or perform perceived abusive clinical
      proceedings. Nurses who experienced higher MD, were more lilely to experience
      burnout. CONCLUSIONS: The modified MDS showed good psychometric properties, and
      it is valid and reliable for assessing moral distress among Italian nurses.
      Hence, the modified MDS allows to monitor the distress experienced by nurses and
      it is an important contribution to the scientific community and all those dealing
      with well-being of health workers.

PMID- 29460563
TI  - ?

PMID- 29460564
TI  - A speck of blood.

PMID- 29460565
TI  - ?

PMID- 29460566
TI  - How are children with asthma treated?

PMID- 29460567
TI  - ?

PMID- 29460568
TI  - ?

PMID- 29460569
TI  - ?

PMID- 29460570
TI  - ?

PMID- 29460571
TI  - ?

PMID- 29460572
TI  - Do we have trustworthy guidelines for clinical practice in Norway?

PMID- 29460573
TI  - ?

PMID- 29460574
TI  - ?

PMID- 29460575
TI  - Guidelines for treatment of sepsis.
AB  - BAKGRUNN: Det finnes internasjonale og nasjonale retningslinjer for behandling av
      sepsis. I tillegg har nesten alle norske sykehus utarbeidet egne retningslinjer
      for behandling av tilstanden. Formalet med denne studien var a vurdere i hvilken
      grad de lokale retningslinjene stemmer overens med de nasjonale. MATERIALE OG
      METODE: Alle offentlige norske sykehus med indremedisinsk akuttfunksjon ble
      kontaktet og forespurt om lokale retningslinjer for behandling av sepsis. De
      lokale retningslinjene ble sammenlignet med nasjonale retningslinjer. RESULTATER:
      43 av 48 sykehus besvarte henvendelsen. 36 sykehus hadde lokale retningslinjer,
      ti av disse hadde retningslinjer utarbeidet ved et storre sykehus. Syv sykehus
      oppga at de brukte nasjonale eller internasjonale retningslinjer direkte, fire av
      disse oppga at deres egne lokale retningslinjer var utdatert eller under
      revisjon. De lokale retningslinjene var i grove trekk samsvarende med de
      nasjonale, selv om flere hadde mindre ulikheter hva gjaldt antibiotikabehandling,
      vaeskebehandling, vasoaktive medikamenter og inotrope medikamenter. FORTOLKNING:
      Majoriteten av norske sykehus hadde lokale retningslinjer for behandling av
      sepsis. De lokale retningslinjene samsvarte godt med de nasjonale, selv om det
      var forskjeller og uenigheter knyttet til enkelte aspekter ved behandlingen.

PMID- 29460578
TI  - ?

PMID- 29460576
TI  - ?

PMID- 29460579
TI  - ?

PMID- 29460580
TI  - Migraine and stroke.
AB  - BAKGRUNN: Migrene er en vanlig nevrologisk sykdom som medforer betydelig
      belastning for den enkelte som rammes, og store helseokonomiske kostnader for
      samfunnet. Migrene er forbundet med okt risiko for hjerneslag. Formalet med denne
      artikkelen er a gi en oversikt over sammenhengen mellom migrene og hjerneslag:
      bade hjerneinfarkt og hjerneblodning, mulige underliggende mekanismer, kliniske
      implikasjoner og behovet for videre forskning innen feltet. KUNNSKAPSGRUNNLAG:
      Denne oversikten er basert pa litteratursok i PubMed med definert sokestreng
      supplert med et pyramidesok i sokemotoren McMaster PLUS med ordene "migraine" og
      "stroke", samt gjennomgang av artiklenes referanselister. RESULTAT: Migrene med
      aura er assosiert med en dobling av risikoen for hjerneinfarkt, men det er ingen
      sikker okt risiko blant personer med migrene uten aura. Royking, p-pillebruk og
      hyppige migreneanfall oker risikoen. Det ser ogsa ut til a vaere en noe hoyere
      forekomst av hjerneblodning hos personer med migrene med og uten aura.
      FORTOLKNING: Sammenhengen mellom migrene og hjerneslag er kompleks. Det er med
      bakgrunn i okt risiko for hjerneinfarkt ved migrene med aura anbefalt at
      modifiserbare risikofaktorer som royking, hypertensjon og p-pillebruk kartlegges
      grundig og behandles.

PMID- 29460581
TI  - ?

PMID- 29460582
TI  - ?

PMID- 29460583
TI  - Misogyny - a silent epidemic in the health service.

PMID- 29460584
TI  - ?

PMID- 29460585
TI  - ?

PMID- 29460586
TI  - ?

PMID- 29460588
TI  - ?

PMID- 29460589
TI  - ?

PMID- 29460590
TI  - ?

PMID- 29460591
TI  - ?

PMID- 29460592
TI  - ?

PMID- 29460593
TI  - When Europe's back door stood open.

PMID- 29460594
TI  - ?

PMID- 29460596
TI  - ?

PMID- 29460598
TI  - ?

PMID- 29460600
TI  - Prescribing of asthma drugs for children 2004-2015.
AB  - BAKGRUNN: Astma kan vaere vanskelig a diagnostisere hos barn. For barn under
      skolealder finnes det fa tilgjengelige objektive diagnostiske undersokelser, og
      retningslinjene for diagnose og behandling er basert pa sykehistorie og klinisk
      undersokelse. Dette kan gi rom for varierende behandlingspraksis. MATERIALE OG
      METODE: Data fra Reseptregisteret ble brukt til a studere forskrivning av
      legemidler mot astma til barn i aldersgruppene 0-4 ar og 5-9 ar fordelt pa fylker
      fra 2004-15. RESULTATER: Det var stor variasjon mellom fylkene i andelen per 1
      000 barn som fikk forskrevet legemidler mot astma i perioden 2012-14
      (aldersgruppen 0-4 ar: median: 104/1 000; ekstremverdier: 64-147, aldersgruppen 5
      9 ar: 68/1000; 46-86). Inhalasjonssteroider var hyppigst forskrevet, og det var
      her variasjonen mellom fylkene var storst i begge aldersgruppene (aldersgruppen 0
      4 ar: 85/1 000; 42-116, aldersgruppen 5-9 ar: 51/1 000; 31-70). De fleste fikk
      kun en eller fa forskrivninger med inhalasjonssteroider over en trearsperiode.
      Endring i forskrivningen av inhalasjonssteroider fra 2004 til 2015 varierte
      betydelig mellom fylkene, mest for aldersgruppen 0-4 ar. FORTOLKNING: Stor
      forskjell i forskrivning av legemidler mot astma fylkene imellom, hoy andel
      sporadisk bruk og endring over tid, saerlig i den yngste aldersgruppen, kan tyde
      pa en unaturlig variasjon i behandlingen som ikke kan forklares av forskjeller i
      astmaforekomst. Uklare retningslinjer som ikke er tilstrekkelig innarbeidet i
      klinisk praksis kan vaere en arsak.

PMID- 29460601
TI  - ?

PMID- 29460602
TI  - ?
AB  - Sarcoidosis is characterised by granulomatous inflammation in one or more organs,
      including the heart. Cardiac sarcoidosis generally has non-specific symptoms, and
      the disease is often diagnosed at a late stage. The condition is associated with
      cardiomyopathy and arrhythmia and may be fatal.

PMID- 29460604
TI  - ?

PMID- 29460605
TI  - ?

PMID- 29460606
TI  - Medical Devices; Cardiovascular Devices; Classification of the Temporary Catheter
      for Embolic Protection During Transcatheter Intracardiac Procedures. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the temporary
      catheter for embolic protection during transcatheter intracardiac procedures 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
      temporary catheter for embolic protection during transcatheter intracardiac
      procedures' 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- 29460607
TI  - Battered child syndrome in the records of the Department of Forensic Medicine,
      Medical University of Bialystok.
AB  - Violence against children has been until now recognised as physical aggression
      escalating from corporal punishment, hard physical labour to homicide. Nowadays
      child abuse is considered as maltreatment occurring in four different aspects:
      physical abuse, psychological abuse, sexual abuse and neglect. Child abuse is
      difficult to disclose, as it is concealed both by the perpetrators and the
      victims. The child is afraid and at the same time, almost always ashamed of
      looking for help. The victim frequently feels guilty, considers the violence as a
      norm, but in many cases is not able to speek precisely and very often has
      problems in contacting the required person. The objective of this study is to
      analyse the phenomenon of child abuse on the basis of Department of Forensic
      Medicine records. The victims were characterized in terms of their age, sex,
      place of residence and the type and location of injuries. The kind of abuse and
      perpetrators were also determined by researchers.

PMID- 29460608
TI  - Estimation of stature from sternal lengths. A correlation meta-analysis.
AB  - AIM OF THE STUDY:: Methods based on the positive linear relationship existing
      between stature and long bones are most commonly used to estimate living stature
      in forensic anthropology. The length of the sternum and its parts has been
      advanced as a plausible alternative to estimate stature when such long bones are
      missing or damaged. MATERIAL AND METHODS: This meta-analysis aims to quantify
      evidence on the correlation between the sternum/sternal parts length and stature.
      Nine studies were included with 1118 sternal bones. RESULTS: Analyses showed that
      the length of the meso-sternum (manubrium + body) yielded the best correlation
      with stature; 53.5% and 55.42% for men and women, respectively. The second best
      variable is the total sternal length with correlations of 44.3% and 55% for men
      and women, respectively. Subgroup analysis of autopsy studies demonstrated even a
      higher correlation of 58.2% for the meso-sternal length. Manubrium and body
      lengths showed the least correlation values. Except for the body length, females
      exhibit a better correlation than man between all other sternal lengths and
      stature. CONCLUSIONS: While the meso-sternal length is found to be the most
      correlated variable with stature, all sternal lengths are to be considered with
      caution when estimating stature. The relatively low values of the weighted
      correlation results should raise the question of reliability and limit the use of
      sternal length when long bones are available. Future research using larger
      samples from different populations and taking into account the fusion status of
      the sternum are needed.

PMID- 29460609
TI  - New psychoactive substances in substantive evidence in expert practice of the
      Department of Forensic Medicine, UJCM in the years 2010-2015.
AB  - AIM OF THE STUDY:: Aim of the study was to analyse of 2075 evidences containing
      new psychoactive substances (NPS). MATERIAL AND METHODS: The prepared samples
      were identified employing an analytical procedure where the analytes were
      investigated by gas chromatography-electron impact mass spectrometry (GC-EI-MS)
      using a created library of mass spectra. RESULTS: The analysis revealed the
      following substances in the investigated products: piperazine derivatives
      (including BZP, MPMP, TFMPP), cathinone derivatives (including: pentedrone, 3
      MMC, butylone, 4-MEC), pyrovalerone derivatives (MDPV, naphyrone, alpha-PVP,
      alpha-PVT), synthetic cannabinoids (such as AM-2201, UR-144, XLR-11, JWH073,
      JWH081, PB-22, AB-CHMINACA). Research conducted in 2010-2015 made it possible to
      track changes in the composition of investigated preparations. CONCLUSIONS: The
      following relationships has been shown: number of components decreased and in the
      end of 2015 dominated preparations with single component; introduction of
      amendments Act on Preventing Drug Addictionn affect the elimination from the
      market of one compounds and replacing them by their derivatives; since 2011 on
      the market of 'legal highs' we did not observe occurrence of compounds of
      piperazine group.

PMID- 29460610
TI  - Vitreous humour - routine or alternative material for analysis in forensic
      medicine.
AB  - Biological materials used in toxicological analyses in forensic medicine
      traditionally include blood, urine and vitreous humour. Forensic use of the
      vitreous body is mostly due to the need to assess the endogenous concentration of
      ethyl alcohol in the process of human body decomposition. The vitreous body is an
      underestimated biological material, even though its biochemical properties and
      anatomical location make it suitable for specific forensic toxicology tests as a
      reliable material for the preparation of forensic expert opinions. Based on the
      available literature the paper gathers information on the biochemical structure
      of the vitreous body, ways to secure the material after collection and its use in
      postmortem diagnostics. Specific applications of the vitreous humour for
      biochemical and toxicological tests are discussed, with a focus on its advantages
      and limitations in forensic medical assessment which are attributable to its
      biochemical properties, anatomical location and limited scientific studies on the
      distribution of xenobiotics in the vitreous body.

PMID- 29460611
TI  - Defendant's or convict's competency to stand trial - forensic psychiatric
      evaluation.
AB  - The purpose of this paper was to draw attention to particularly important aspects
      of pronouncing forensic psychiatric judgment regarding the accused or convicted
      individuals' competency to stand trial. The level of a person's mental capacity
      should be established using a structured psychiatric interview concerning a
      variety of aspects of a trial. Emphasis should be placed on evaluating the
      defendant's consciousness of the charges, knowledge of the potential punishment,
      ability to make significant decisions and be engaged in defense, knowledge about
      the role that particular people present in the courtroom play, understanding of
      the meaning of the evidence gathered in the case, the risk of aggression. The
      analysis should take into account the specificity of the mental disorder, the
      influence of proceedings on the course of disorder, as well as the presence of
      reactive disorders. Using testing tools by the expert can facilitate the process
      of evaluation to a certain degree. Forensic psychiatric evaluations can give rise
      to difficulties for the experts, what with the changing legal regulations and
      their interpretations. It would be justified to develop the standards of
      evaluation in this kind of cases, which would on the one hand apply to experts
      but which would also be respected by the judicial organ.

PMID- 29460612
TI  - SNPs and STRs in forensic medicine. A strategy for kinship evaluation.
AB  - Some emerging technologies are used as strategies for the analyses of single
      nucleotide polymorphisms (SNPs) that have attracted much interest in recent
      years, applied to various scientific areas. They have been extensively used as
      markers to identify genes that underlie complex diseases and also to realize the
      potential of pharmacogenomics in relation to different drug responses.
      Additionally, SNPs have been shown to be very useful in forensic genetics
      resolving all kinds of legal problems, namely crime cases, disaster victim
      identification and paternity and kinship investigation testing. The low mutation
      rate of SNPs, makes these markers very suitable for relationship testing. In the
      great majority of the cases, analyses with the widely used sets of STR markers
      provide powerful statistical evidence but some of them remain with ambiguous
      results. Those include cases with complex pedigrees or cases with some problems,
      like mutations, that are inherent to the use of STRs. At this time several
      forensic laboratories are using SNPs especially to complement the study of STRs
      in some of their casework cases. This paper intends to analyze some of our
      casework examples and to providea data update on the joint use of STRs and
      autosomal SNPs in the evaluation and kinship calculation, one of the strategies
      currently used for this purpose, namely reviewing and comparing results published
      by various working groups.

PMID- 29460613
TI  - Medical Devices; General and Plastic Surgery Devices; Classification of the
      Surgical Smoke Precipitator. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the surgical smoke
      precipitator 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 surgical smoke precipitator'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- 29460614
TI  - Influences of Conjugation Length on Organic Field-Effect Transistor Performances
      and Thin Film Structures of Diketopyrrolopyrrole-Oligomers.
AB  - Here, two diketopyrrolopyrrole (DPP)-based oligomers, DPP-4T and DPP-6T, are
      studied to reveal the influences of conjugation length on thin-film morphology
      and organic field-effect transistor (OFET) performances. PDMS-assisted
      crystallization in a solvent-annealing chamber is applied to prepare crystal
      arrays of DPP-4T and DPP-6T to optimize the quality of charge channels for OFET
      characterizations. To deliver insights into microstructure and morphology of thin
      films, a characterization procedure for determining molecular packing in thin
      film and crystallinity of the crystal arrays is presented via grazing incidence
      wide-angle X-ray scattering, electron diffraction, and lattice simulation
      software package (Cerius2). With the lattice parameters derived from analyses of
      grazing incidence wide-angle X-ray scattering (GIWAXS) and electron diffraction
      (ED), the lattice modeling results indicate that the inferior organic field
      effect transistor (OFET) performances of DPP-6T are attributed to longer pi
      stacking distance. Also, less-ordered molecular arrangement and lower continuity
      of crystalline domains, both of which are revealed from crystallinity results,
      lead to lower mobility of DPP-6T. In this case, longer conjugated backbones with
      more conformational degrees of freedom thus cause inherent crystal defects during
      the crystal growth process, despite the potential to enhance intermolecular pi
      orbital overlap. Therefore, to achieve better OFET performance, suitable backbone
      length makes conjugated oligomers give high intermolecular pi-orbital overlap and
      low density of structural disorder, which are the priorities for constructing
      good charge channel.

PMID- 29460616
TI  - Highly Efficient Thermoelectric Microgenerators Using Nearly Room Temperature
      Pulsed Laser Deposition.
AB  - Thermoelectric Bi2Te3 and Sb2Te3 thin films with high power factor were
      successfully obtained by pulsed laser deposition (PLD). Here, we demonstrate a
      well-controlled deposition of Bi2Te3/Sb2Te3 structures on glass substrates,
      through a shadow mask with micrometer-scale features. We establish an optimal
      growth temperature of 45  degrees C to attain compounds with suitable
      stoichiometric composition, as well as structural and electrical properties, to
      achieve high thermoelectric power factor. These films are produced without
      additional postannealing treatment or added gases. Indeed, crystalline films with
      Seebeck coefficients of 624 and -78 MUV K-1 are obtained for Sb2Te3 and Bi2Te3,
      respectively. Microgenerators consisting of four pairs of n-type Bi2Te3 and p
      type Sb2Te3 legs connected in series generate a maximum voltage of 50 mV and a
      power density of around 120 MUW cm-2 for a temperature difference of 30 K across
      the hot and cold ends of the device. This low-temperature and simple PLD
      deposited device represents an important step toward practical thermoelectric
      materials as well as efficient and compact microgenerators for low-temperature
      energy-harvesting applications.

PMID- 29460617
TI  - Pharmacological Inhibition of O-GlcNAcase Enhances Autophagy in Brain through an
      mTOR-Independent Pathway.
AB  - The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine
      residues (O-GlcNAc) is conserved among metazoans and is particularly abundant
      within brain. O-GlcNAc is involved in diverse cellular processes ranging from the
      regulation of gene expression to stress response. Moreover, O-GlcNAc is
      implicated in various diseases including cancers, diabetes, cardiac dysfunction,
      and neurodegenerative diseases. Pharmacological inhibition of O-GlcNAcase (OGA),
      the sole enzyme that removes O-GlcNAc, reproducibly slows neurodegeneration in
      various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid
      pathology. These data have stimulated interest in the possibility of using OGA
      selective inhibitors as pharmaceuticals to alter the progression of AD. The
      mechanisms mediating the neuroprotective effects of OGA inhibitors, however,
      remain poorly understood. Here we show, using a range of methods in neuroblastoma
      N2a cells, in primary rat neurons, and in mouse brain, that selective OGA
      inhibitors stimulate autophagy through an mTOR-independent pathway without
      obvious toxicity. Additionally, OGA inhibition significantly decreased the levels
      of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy
      mouse model as well as the 3*Tg-AD mouse model. These results strongly suggest
      that OGA inhibitors act within brain through a mechanism involving enhancement of
      autophagy, which aids the brain in combatting the accumulation of toxic protein
      species. Our study supports OGA inhibition being a feasible therapeutic strategy
      for hindering the progression of AD and other neurodegenerative diseases.
      Moreover, these data suggest more targeted strategies to stimulate autophagy in
      an mTOR-independent manner may be found within the O-GlcNAc pathway. These
      findings should aid the advancement of OGA inhibitors within the clinic.

PMID- 29460615
TI  - Precursor-Receptor Interactions in the Twin Arginine Protein Transport Pathway
      Probed with a New Receptor Complex Preparation.
AB  - The twin arginine translocation (Tat) system moves folded proteins across the
      cytoplasmic membrane of bacteria and the thylakoid membrane of plant
      chloroplasts. Signal peptide-bearing substrates of the Tat pathway (precursor
      proteins) are recognized at the membrane by the TatBC receptor complex. The only
      established preparation of the TatBC complex uses the detergent digitonin,
      rendering it unsuitable for biophysical analysis. Here we show that the detergent
      glyco-diosgenin (GDN) can be used in place of digitonin to isolate homogeneous
      TatBC complexes that bind precursor proteins with physiological specificity. We
      use this new preparation to quantitatively characterize TatBC-precursor
      interactions in a fully defined system. Additionally, we show that the GDN
      solubilized TatBC complex co-purifies with substantial quantities of
      phospholipids.

PMID- 29460618
TI  - Biosynthesis of Phenylglyoxylic Acid by LhDMDH, a Novel d-Mandelate Dehydrogenase
      with High Catalytic Activity.
AB  - d-Mandelate dehydrogenase (DMDH) has the potential to convert d-mandelic acid to
      phenylglyoxylic acid (PGA), which is a key building block in the field of
      chemical synthesis and is widely used to synthesize pharmaceutical intermediates
      or food additives. A novel NAD+-dependent d-mandelate dehydrogenase was cloned
      from Lactobacillus harbinensi (LhDMDH) by genome mining and expressed in
      Escherichia coli BL21. After being purified to homogeneity, the oxidation
      activity of LhDMDH toward d-mandelic acid was approximately 1200 U.mg-1, which
      was close to four times the activity of the probe. Meanwhile, the kcat/ Km value
      of LhDMDH was 28.80 S-1.mM-1, which was distinctly higher than the probe. By
      coculturing two E. coli strains expressing LhDMDH and LcLDH, we developed a
      system for the efficient synthesis of PGA, achieving a 60% theoretical yield and
      99% purity without adding coenzyme or cosubstrate. Our data supports the
      implementation of a promising strategy for the chiral resolution of racemic
      mandelic acid and the biosynthesis of PGA.

PMID- 29460619
TI  - Ring Opening Polymerization and Copolymerization of Cyclic Esters Catalyzed by
      Group 2 Metal Complexes Supported by Functionalized P-N Ligands.
AB  - We report the preparation of alkali and alkaline earth (Ae) metal complexes
      supported by 2-picolylamino-diphenylphosphane chalcogenide
      [(Ph2P(=E)NHCH2(C5H4N)] [E = S (1-H); Se (2-H)] ligands. The treatment of the
      protic ligand, 1-H or 2-H, with alkali metal hexamethyldisilazides at room
      temperature afforded the corresponding alkali metal salts
      [M(THF)2(Ph2P(=E)NCH2(C5H4N)] [M = Li, E = S (3a), Se (3b)] and [{M(THF)
      n(Ph2P(=E)NCH2(C5H4N)}2] [M = Na, E = S (4a), Se (4b); M = K, E = Se (5b)] in
      good yield. The homoleptic Ae metal complexes [kappa2
      (Ph2P(=Se)NCH2(C5H4N)Mg(THF)] (6b) and [kappa3-{(Ph2P(=Se)NCH2(C5H4N)}2M(THF) n]
      (M = Ca (7b), Sr (8b), Ba (9b)] were synthesized by the one-pot reaction of 2-H
      with [KN(SiMe3)2] and MI2 in a 2:2:1 molar ratio at room temperature. The
      molecular structures of the protic-ligands 1-H and 2-H, as well as complexes 3a,b
      5a,b and 6b-9b were established using single-crystal X-ray analysis. The Ae metal
      complexes 6b-9b were tested for ring-opening polymerization (ROP) of racemic
      lactide ( rac-LA) and copolymerization of rac-LA and epsilon-caprolactone
      (epsilon-CL) at room temperature. In the ROP of rac-LA, the calcium complex 7b
      exhibited high isoselectivity, with Pi = 0.89, whereas both the barium and
      strontium complexes showed lower isoselectivity with Pi = 0.78-0.62. In the
      copolymerization of rac-LA and epsilon-CL, both barium and strontium complexes
      proved to be efficient precatalysts for the formation of the block copolymer rac
      LA-CL, but the reactivity of 9b was found to be better than that of 8b. All the
      polymers were fully characterized using differential scanning calorimetry,
      thermogravimetric analysis, and gel permeation chromatography analyses. Kinetic
      studies on the ROP reaction of LA confirmed that the rate of polymerization
      followed the order Ba ? Sr ~ Ca.

PMID- 29460620
TI  - Development of Smart Optical Gels with Highly Magnetically Responsive Bicelles.
AB  - Hydrogels delivering on-demand tailorable optical properties are formidable smart
      materials with promising perspectives in numerous fields, including the
      development of modern sensors and switches, the essential quality criterion being
      a defined and readily measured response to environmental changes. Lanthanide ion
      (Ln3+)-chelating bicelles are interesting building blocks for such materials
      because of their magnetic responsive nature. Imbedding these phospholipid-based
      nanodiscs in a magnetically aligned state in gelatin permits an orientation
      dependent retardation of polarized light. The resulting tailorable anisotropy
      gives the gel a well-defined optical signature observed as a birefringence
      signal. These phenomena were only reported for a single bicelle-gelatin pair and
      required high magnetic field strengths of 8 T. Herein, we demonstrate the
      versatility and enhance the viability of this technology with a new generation of
      aminocholesterol (Chol-NH2)-doped bicelles imbedded in two different types of
      gelatin. The highly magnetically responsive nature of the bicelles allowed to gel
      the anisotropy at commercially viable magnetic field strengths between 1 and 3 T.
      Thermoreversible gels with a unique optical signature were generated by exposing
      the system to various temperature conditions and external magnetic field
      strengths. The resulting optical properties were a signature of the gel's
      environmental history, effectively acting as a sensor. Solutions containing the
      bicelles simultaneously aligning parallel and perpendicular to the magnetic field
      directions were obtained by mixing samples chelating Tm3+ and Dy3+. These systems
      were successfully gelled, providing a material with two distinct temperature
      dependent optical characteristics. The high degree of tunability in the magnetic
      response of the bicelles enables encryption of the gel's optical properties. The
      proposed gels are viable candidates for temperature tracking of sensitive goods
      and provide numerous perspectives for future development of tomorrow's smart
      materials and technologies.

PMID- 29460621
TI  - Differential Protein Dynamics of Regulators of G-Protein Signaling: Role in
      Specificity of Small-Molecule Inhibitors.
AB  - Small-molecule inhibitor selectivity may be influenced by variation in dynamics
      among members of a protein family. Regulator of G-protein Signaling (RGS)
      proteins are a family that plays a key role in G-Protein Coupled Receptor (GPCR)
      signaling by binding to active Galpha subunits and accelerating GTP hydrolysis,
      thereby terminating activity. Thiadiazolidinones (TDZDs) inhibit the RGS-Galpha
      interaction by covalent modification of cysteine residues in RGS proteins. Some
      differences in specificity may be explained by differences in the complement of
      cysteines among RGS proteins. However, key cysteines shared by RGS proteins
      inhibited by TDZDs are not exposed on the protein surface, and differences in
      potency exist among RGS proteins containing only buried cysteines. We hypothesize
      that differential exposure of buried cysteine residues among RGS proteins
      partially drives TDZD selectivity. Hydrogen-deuterium exchange (HDX) studies and
      molecular dynamics (MD) simulations were used to probe the dynamics of RGS4,
      RGS8, and RGS19, three RGS proteins inhibited at a range of potencies by TDZDs.
      When these proteins were mutated to contain a single, shared cysteine, RGS19 was
      found to be most potently inhibited. HDX studies revealed differences in alpha4
      and alpha6 helix flexibility among RGS isoforms, with particularly high
      flexibility in RGS19. This could cause differences in cysteine exposure and lead
      to differences in potency of TDZD inhibition. MD simulations of RGS proteins
      revealed motions that correspond to solvent exposure observed in HDX, providing
      further evidence for a role of protein dynamics in TDZD selectivity.

PMID- 29460622
TI  - Influence of UGT2B10 Genotype on Urinary Excretion of 4-(Methylnitrosamino)-1-(3
      pyridyl)-1-butanol- N-glucuronide by African American Smokers.
AB  - At similar smoking levels, African American's lung cancer risk is as much as
      twice that of whites. We hypothesized that racial/ethnic differences in UDP
      glucuronosyltransferase (UGT)-catalyzed glucuronidation of 4-(methylnitrosamino)
      1-(3-pyridyl)-1-butanol (NNAL), a detoxication pathway for the tobacco-specific
      lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) may
      contribute to this variable risk. UGT2B10 catalyzes NNAL- N-glucuronidation, and
      a UGT2B10 splice variant is common among African Americans. Smokers from two
      independent studies were genotyped for this variant (rs116294140) and an Asp67Tyr
      variant (rs61750900), and urinary NNAL and NNAL-glucuronide concentrations were
      quantified. In the first, no significant differences in NNAL- N-glucuronidation
      between African Americans ( n = 257) and whites ( n = 354) or between homozygous
      carriers of UGT2B10 variants (genetic score 2) and noncarriers (score 0) were
      detected. However, total NNAL glucuronidation by score 2 compared to score 0
      smokers was lower (68.9 vs 71.2%, p < 0.0001). For NNAL- N-glucuronide to be more
      precisely quantified in a second study, a sensitive high-resolution LC-MS/MS
      based method, which separated NNAL, NNAL- O-glucuronide, and NNAL- N-glucuronide
      prior to analysis, was developed. In this study, the excretion of total NNAL
      (free plus glucuronides) by African American ( n = 52) and white ( n = 54)
      smokers was not different; however, total NNAL glucuronidation by African
      Americans (64.0%) was slightly less than by whites (68.3%, p = 0.05). The mean
      NNAL- N-glucuronidation by African Americans was much lower than for whites (14
      vs 24.9%, p < 0.00001), but the NNAL- O-glucuronidation was greater (50.0 vs
      43.3%, p = 0.013). UGT2B10 genotype influenced NNAL- N-glucuronidation; the
      geometric mean percentage N-glucuronidation was 22.5% for smokers with genetic
      score 0 ( n = 57) and 11.2% for score 2 ( n = 11). In summary, the high
      prevalence of a UGT2B10 splice variant among African Americans results in lower
      NNAL- N-glucuronidation but only a small decrease in total NNAL glucuronidation.
      Therefore, despite the significant contribution of UGT2B10 to NNAL- N
      glucuronidation, the UGT2B10 genotype does not play a large role in NNAL
      detoxication. Any decrease in N-glucuronidation was accompanied by a parallel
      increase in O-glucuronidation.

PMID- 29460623
TI  - Generation and Reactivity of Electron-Rich Carbenes on the Surface of Catalytic
      Gold Nanoparticles.
AB  - The reactive nature of carbenes can be modulated, and ultimately reversed, by
      receiving additional electron density from a metal. Here, it is shown that Au
      nanoparticles (NPs) generate an electron-rich carbene on surface after
      transferring electron density to the carbonyl group of an in situ activated
      diazoacetate, as assessed by Fourier transformed infrared (FT-IR) spectroscopy,
      magic angle spinning nuclear magnetic resonance (MAS NMR), and Raman
      spectroscopy. Density functional theory (DFT) calculations support the observed
      experimental values and unveil the participation of at least three different Au
      atoms during carbene stabilization. The surface stabilized carbene shows an
      extraordinary stability against nucleophiles and reacts with electrophiles to
      give new products. These findings showcase the ability of catalytic Au NPs to
      inject electron density in energetically high but symmetrically allowed valence
      orbitals of sluggish molecules.

PMID- 29460624
TI  - Multifunctional Nickel Phosphate Nano/Microflakes 3D Electrode for
      Electrochemical Energy Storage, Nonenzymatic Glucose, and Sweat pH Sensors.
AB  - Multifunctional, low-cost electrodes and catalysts are desirable for next
      generation electrochemical energy-storage and sensor applications. In this study,
      we demonstrate the fabrication of Ni3(PO4)2.8H2O nano/microflakes layer on nickel
      foam (NF) by a facile one-pot hydrothermal approach and investigate this
      electrode for multiple applications, including sweat-based glucose and pH sensor
      as well as hybrid energy-storage device, e.g., supercapattery. The electrode
      displays a specific capacity of 301.8 mAh g-1 (1552 F g-1) at an applied current
      of 5 mA cm-2 and can retain 84% of its initial capacity after 10 000 cycles.
      Furthermore, the supercapattery composed of Ni3(PO4)2.8H2O/NF as positive
      electrode and activated carbon as negative electrode can offer a high specific
      energy of 33.4 Wh kg-1 with the power of 165.5 W kg-1. As an electrocatalyst for
      nonenzymatic glucose sensor, Ni3(PO4)2.8H2O/NF shows an exceptional sensitivity
      (24.39 mA mM-1cm-2) with a low detection limit of 97 nM (S/N = 3). Moreover, as a
      sweat-based pH sensor, the electrode is capable of detecting human sweat pH
      values ranging from 4 to 7. Therefore, this three-dimensional nanoporous
      Ni3(PO4)2.8H2O/NF electrode, due to its excellent electrochemical performance,
      can be successfully applied in electrochemical energy-storage and biosensor
      applications.

PMID- 29460625
TI  - Immobilized FhuD2 Siderophore-Binding Protein Enables Purification of Salmycin
      Sideromycins from Streptomyces violaceus DSM 8286.
AB  - Siderophores are a structurally diverse class of natural products common to most
      bacteria and fungi as iron(III)-chelating ligands. Siderophores, including
      trihydroxamate ferrioxamines, are used clinically to treat iron overload diseases
      and show promising activity against many other iron-related human diseases. Here,
      we present a new method for the isolation of ferrioxamine siderophores from
      complex mixtures using affinity chromatography based on resin-immobilized FhuD2,
      a siderophore-binding protein (SBP) from Staphylococcus aureus. The SBP-resin
      enabled purification of charge positive, charge negative, and neutral
      ferrioxamine siderophores. Treatment of culture supernatants from Streptomyces
      violaceus DSM 8286 with SBP-resin provided an analytically pure sample of the
      salmycins, a mixture of structurally complex glycosylated sideromycins
      (siderophore-antibiotic conjugates) with potent antibacterial activity toward
      human pathogenic Staphylococcus aureus (minimum inhibitory concentration (MIC) =
      7 nM). Siderophore affinity chromatography could enable the rapid discovery of
      new siderophore and sideromycin natural products from complex mixtures to aid
      drug discovery and metabolite identification efforts in a broad range of
      therapeutic areas.

PMID- 29460626
TI  - Correlation of Device Performance and Fermi Level Shift in the Emitting Layer of
      Organic Light-Emitting Diodes with Amine-Based Electron Injection Layers.
AB  - We investigate three amine-based polymers, polyethylenimine and two amino
      functionalized polyfluorenes, as electron injection layers (EILs) in organic
      light-emitting diodes (OLEDs) and find correlations between the molecular
      structure of the polymers, the electronic alignment at the emitter/EIL interface,
      and the resulting device performance. X-ray photoelectron spectroscopy
      measurements of the emitter/EIL interface indicate that all three EIL polymers
      induce an upward shift of the Fermi level in the emitting layer close to the
      interface similar to n-type doping. The absolute value of this Fermi level shift,
      which can be explained by an electron transfer from the EIL polymers into the
      emitting layer, correlates with the number of nitrogen-containing groups in the
      side chains of the polymers. Whereas polyethylenimine (PEI) and one of the
      investigated polyfluorenes (PFCON-C) have six such groups per monomer unit, the
      second investigated polyfluorene (PFN) only possesses two. Consequently, we
      measure Fermi level shifts of 0.5-0.7 eV for PEI and PFCON-C and only 0.2 eV for
      PFN. As a result of these Fermi level shifts, the energetic barrier for electron
      injection is significantly lowered and OLEDs which comprise PEI or PFCON-C as an
      EIL exhibit a more than twofold higher luminous efficacy than OLEDs with PFN.

PMID- 29460627
TI  - Pd Metal Catalysts for Cross-Couplings and Related Reactions in the 21st Century:
      A Critical Review.
AB  - Cross-couplings and related reactions are a class of highly efficient synthetic
      protocols that are generally promoted by molecular Pd species as catalysts.
      However, catalysts based on more or less highly dispersed Pd metal have been also
      employed for this purpose, and their use, which was largely limited to the Heck
      reaction until the turn of the century, has been extended in recent years to most
      reactions of this class. This review provides a critical overview on these recent
      applications of Pd metal catalysts. Particular attention is devoted to the
      discussion of the mechanistic pathways that have been proposed to explain the
      catalytic role of Pd metal. Furthermore, the most outstanding Pd metal based
      catalytic systems that have emerged are illustrated, together with the
      development of novel approaches to boost the reactivity of Pd metal. A section
      summarizing the current industrial applications of Pd metal catalyzed reactions
      of this kind concludes the review.

PMID- 29460628
TI  - Eight Inch Wafer-Scale Flexible Polarization-Dependent Color Filters with Ag-TiO2
      Composite Nanowires.
AB  - In this study, 8 in. wafer-scale flexible polarization-dependent color filters
      with Ag-TiO2 composite nanowires have been fabricated using nanoimprint and E
      beam evaporation. The filters change their color via a simple rotation of the
      polarizer. In addition, the color of the filter can be controlled by altering the
      thickness of the Ag and TiO2 nanowires deposited on the polymer patterns.
      Polarization-dependent color filters were realized by selective inhibition of
      transmission using the plasmonic resonance at the insulator/metal/insulator
      nanostructure interface, which occurs at particular wavelengths for the
      transverse magnetic polarizations. Special colors, including purple, blue, green,
      yellow, and pink, could be obtained with high transmission beyond 65% by varying
      the thickness of the deposited Ag and TiO2 nanowires on the periodic polymer
      pattern under transverse magnetic polarization. In addition, a continuous color
      change was achieved by varying the polarization angle. Last, numerical
      simulations were implemented in comparison with the experimental results, and the
      mechanism was explained. We believe that this simple and cost-effective method
      can be applied to processes such as anticounterfeiting and holographic imaging as
      well as to color displays.

PMID- 29460629
TI  - Structural Evolution of a Retinal Chromophore in the Photocycle of Halorhodopsin
      from Natronobacterium pharaonis.
AB  - We revealed the chloride ion pumping mechanism in halorhodopsin from
      Natronobacterium pharaonis ( pHR) by exploring sequential structural changes in
      the retinal chromophore during its photocycle using time-resolved resonance Raman
      (RR) spectroscopy on the nanosecond to millisecond time scales. A series of RR
      spectra of the retinal chromophore in the unphotolyzed state and of the three
      intermediates of pHR were obtained. Using singular value decomposition analysis
      of the C?C and C-C stretch bands in the time-resolved RR spectra, we identified
      the spectra of the K, L, and N intermediates. We focused on structural markers of
      the RR bands to explore the structure of the retinal chromophore. In the
      unphotolyzed state, the retinal chromophore is in the planar all- trans, 15- anti
      geometry. The bound ion affects the polyene chain but does not interact with the
      protonated Schiff base. In the observed intermediates, the chromophore is in the
      13- cis configuration. The chromophore in the K intermediate is distorted due to
      the photoisomerization of retinal. The hydrogen bond is weak in the unphotolyzed
      state and in the K intermediate, resulting in exchange of the hydrogen-bond
      acceptor to a water molecule in the K-to-L transition, relaxation of the polyene
      chain distortion, and generation of an alternative distortion near the Schiff
      base. The bound halide ion interacts with the protonated Schiff base through the
      water molecule bound to the protonated Schiff base. In the L-to-N transition, the
      hydrogen acceptor of the protonated Schiff base switches from the water molecule
      to another species, although the strong hydrogen bond of the protonated Schiff
      base remains. This paper reports the first observation of sequential changes in
      the RR spectra in the pHR photocycle, provides information on the structural
      evolution of the retinal chromophore, and proposes a model for chloride ion
      translocation in pHR.

PMID- 29460630
TI  - Insights on the Origin of Catalysis on Glycine N-Methyltransferase from
      Computational Modeling.
AB  - The origin of enzyme catalysis remains a question of debate despite much intense
      study. We report a QM/MM theoretical study of the SN2 methyl transfer reaction
      catalyzed by a glycine N-methyltransferase (GNMT) and three mutants to test
      whether recent experimental observations of rate-constant reductions and
      variations in inverse secondary alpha-3H kinetic isotope effects (KIEs) should be
      attributed to changes in the methyl donor-acceptor distance (DAD): Is catalysis
      due to a compression effect? Semiempirical (AM1) and DFT (M06-2X) methods were
      used to describe the QM subset of atoms, while OPLS-AA and TIP3P classical force
      fields were used for the protein and water molecules, respectively. The computed
      activation free energies and KIEs are in good agreement with experimental data,
      but the mutations do not meaningfully affect the DAD: Compression cannot explain
      the experimental variations on KIEs. On the contrary, electrostatic properties in
      the active site correlate with the catalytic activity of wild type and mutants.
      The plasticity of the enzyme moderates the effects of the mutations, explaining
      the rather small degree of variation in KIEs and reactivities.

PMID- 29460631
TI  - Oxidative Dephosphorylation of Benzylic Phosphonates with Dioxygen Generating
      Symmetrical trans-Stilbenes.
AB  - Under a dioxygen atmosphere, benzylphosphonates and related phosphoryl compounds
      can readily produce the corresponding trans-stilbenes in high yields with high
      selectivity upon treatment with bases. Various functional groups were tolerable
      under the reaction conditions.

PMID- 29460632
TI  - Structural Ordering of Molybdenum Disulfide Studied via Reactive Molecular
      Dynamics Simulations.
AB  - Molybdenum disulfide (MoS2) is a well-known and effective lubricant that provides
      extremely low values of coefficient of friction. It is known that the sliding
      process may induce structural transformations of amorphous or disordered MoS2 to
      the crystalline phase with basal planes oriented parallel to the sliding
      direction, which is optimal for reducing friction. However, the key reaction
      parameters and conditions promoting this structural transformation are still
      largely unknown. We investigate, by employing reactive molecular dynamics
      simulations, the formation of MoS2 layers from an amorphous phase as a function
      of temperature, initial sample density, and sliding velocity. We show that the
      formation of ordered crystalline structures can be explained in the framework of
      classical nucleation theory as it predicts the conditions for their nucleation
      and growth. These results may have important implications in the fields of
      coating and thin-film deposition, tribology, and in all technological
      applications where a fast and effective structural transition to an ordered phase
      is needed.

PMID- 29460633
TI  - Catalytic Enantioselective Synthesis of a Pyrrolizidine-Alkaloid-Inspired
      Compound Collection with Antiplasmodial Activity.
AB  - A novel enantioselective approach to the synthesis of a compound collection
      inspired by natural pyrrolizidine alkaloids was developed, employing an
      enantioselectively catalyzed 1,3-dipolar cycloaddition as the key step. The
      cycloadducts were obtained with excellent enantio- and diastereoselectivity.
      Biological evaluation of the resulting compound collection revealed that the
      compound class has multiple bioactivities, including activity against Plasmodium
      falciparum 3D7 and inhibition of Hedgehog signaling.

PMID- 29460634
TI  - Serum Metabolomics Study of Gliclazide-Modified-Release-Treated Type 2 Diabetes
      Mellitus Patients Using a Gas Chromatography-Mass Spectrometry Method.
AB  - Sulfonylureas are one of the commonly used drugs in type 2 diabetes mellitus
      (T2DM) but with considerable incidence of monotherapy failure. However, the
      mechanism of patients' drug response is unclear, and suitability evaluation
      biomarkers are in urgent need for precision medicine. In this study, a
      pseudotargeted gas chromatography-mass spectrometry method was employed to
      investigate the serum metabolic profiling of 66 significant responders and 24
      nonsignificant responders at baseline and 16 weeks after gliclazide modified
      release (MR) monotherapy. Clinical improvements in blood glucose level and
      insulin sensitivity were closely associated with the alterations of TCA cycle,
      ketone body metabolism, lipid oxidation, branched-chain amino acid catabolism,
      and gut flora metabolism. The different baseline metabolic profiling observed in
      the two groups implied that patients with lower dyslipidemia level may be more
      suitable for sulfonylurea therapy. The biomarker panel consisting of HbA1c,
      5,8,11,14,17-eicosapentaenoic acid, methyl 8,11,14-eicosatrienoate, and methyl
      hexadecanoate shows a very good prediction ability for the suitability of
      gliclazide treatment, and it may be meaningful in personalized medicine of T2DM
      patients by sulfonylurea therapy.

PMID- 29460635
TI  - Nivolumab in the treatment of advanced renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) has typically been considered an immunogenic
      malignancy with responses seen to IL-2 and IFN-alpha. Response rates, however,
      were low and at the cost of considerable toxicity and as such, agents targeting
      angiogenesis have become the mainstay of treatment. Nivolumab is an immune
      checkpoint inhibitor targeting PD-1 thereby upregulating the host immune response
      against tumor cells. Nivolumab has emerged as a promising new therapy in advanced
      malignancies, and the first agent to show survival advantage in patients failing
      prior VEGFR-targeted therapy in metastatic RCC. This review summarizes the
      present evidence, toxicity profile, potential predictive biomarkers and promising
      future strategies with nivolumab in metastatic RCC.

PMID- 29460636
TI  - Neurological, physical and sociodemographic correlates of employment in multiple
      sclerosis: A meta-analysis.
AB  - Illness severity and sociodemographic characteristics of 7,053 employees with
      multiple sclerosis and 11,043 peers not in the workforce were compared (Hedges' g
      with 95% confidence interval and p values). Pooled findings from 25 studies
      confirmed the main role of a relapsing-remitting disease course and higher
      education to employment. To a lesser extent, disease duration, fatigue and pain
      symptoms and age also differentiated the two groups. Vocational interventions for
      persons with multiple sclerosis should focus on job retention, including
      mechanisms to accommodate and facilitate functional independence. Longitudinal
      data are needed to distinguish the characteristics of those who achieve and
      maintain competitive employment.

PMID- 29460637
TI  - Hospital usage of TOXBASE in Great Britain: Temporal trends in accesses 2008 to
      2015.
AB  - AIM: To examine temporal trends in accesses to the UK's National Poison
      Information Service's TOXBASE database in Britain. METHODS: Generalized additive
      models were used to examine trends in daily numbers of accesses to TOXBASE from
      British emergency departments between January 2008 and December 2015. Day-of-the
      week, seasonality and long-term trends were analysed at national and regional
      levels (Wales, Scotland and the nine English Government Office Regions). RESULTS:
      The long-term trend in daily accesses increases from 2.8 (95% confidence interval
      (CI): 2.6-3.0) per user on 1 January 2008 to 4.6 (95% CI: 4.3-4.9) on 31 December
      2015, with small but significant differences in population-corrected accesses by
      region ( p < 0.001). There are statistically significant seasonal and day of the
      week patterns ( p < 0.001) across all regions. Accesses are 18% (95% CI: 14-22%)
      higher in summer than in January and at the weekend compared to weekdays in all
      regions; there is a 7.5% (95% CI: 6.1-8.9%) increase between Friday and Sunday.
      CONCLUSIONS: There are consistent in-year patterns in access to TOXBASE
      indicating potential seasonal patterns in poisonings in Britain, with location
      dependent rates of usage. This novel descriptive work lays the basis for future
      work on the interaction of TOXBASE use with emergency admission of patients into
      hospital.

PMID- 29460638
TI  - Effectiveness of a Pediatric Abusive Head Trauma Prevention Program Among Spanish
      Speaking Mothers.
AB  - INTRODUCTION: This study aimed to evaluate participants' knowledge of and intent
      to share key messages of the Period of PURPLE Crying abusive head trauma
      prevention program among a majority Spanish-speaking population. METHODS: This
      study was a retrospective review of a postintervention survey administered in the
      perinatal unit of a community birthing hospital. Surveys were administered to
      mothers of newborns by perinatal nurses as part of routine process evaluation
      prior to hospital discharge between May 30, 2014, and May 15, 2015. RESULTS: A
      majority of participants (86.4%) answered all six knowledge questions correctly.
      Among participants who reported that the father or significant other was not
      present during the PURPLE education (44.1%), all (100%) reported intending to
      share the PURPLE information with their partners. The majority of participants
      (88.1%) intended to share the information with others who take care of their
      infants. CONCLUSION: The PURPLE abusive head trauma prevention program
      demonstrated positive preliminary results in knowledge and intended behavior
      among a population of majority Spanish-speaking participants. These findings
      offer an important first step toward provision of effective universal abusive
      head trauma prevention among growing Spanish-speaking populations. Further
      evaluation is needed of acceptability, retention of messages, and
      postintervention behavior change among Spanish-speaking participants and nurses.

PMID- 29460639
TI  - Planning Telehealth for Older Adults With Atrial Fibrillation in Rural
      Communities: Understanding Stakeholder Perspectives.
AB  - Older adults with atrial fibrillation (AF) in rural communities have less access
      to cardiac specialty care. Telehealth offers a viable approach to provide cardiac
      care, yet little is known about patients' and providers' views on telehealth's
      potential to support rural patients with AF. This qualitative descriptive study
      examines patient and health providers' perspectives, an important first step in
      planning a telehealth initiative. Eight patients with AF, along with one partner
      from rural communities, were recruited through an urban-based AF clinic. Five
      providers were recruited through professional practice leads in the health
      region. Semistructured telephone interviews were conducted with both stakeholder
      groups. The overriding theme was variability in patient and provider
      receptiveness to telehealth. Receptiveness reflected differences in past
      experience with telehealth, in perceived adequacy of rural health services, and
      in perceived gaps in AF care. These are important considerations in planning
      effective and sustainable telehealth in rural communities.

PMID- 29460640
TI  - Implications of HLA-allele associations for the study of type IV drug
      hypersensitivity reactions.
AB  - INTRODUCTION: Type IV drug hypersensitivity remains an important clinical problem
      and an obstacle to the development of new drugs. Several forms of drug
      hypersensitivity are associated with expression of specific HLA alleles.
      Furthermore, drug-specific T-lymphocytes have been isolated from patients with
      reactions. Despite this, controversy remains as to how drugs interact with immune
      receptors to stimulate a T-cell response. Areas covered: This article reviews the
      pathways of T-cell activation by drugs and how the ever increasing number of
      associations between expression of HLA alleles and susceptibility to
      hypersensitivity is impacting on our research effort to understanding this form
      of iatrogenic disease. Expert opinion: For a drug to activate a T-cell, a complex
      is formed between HLA molecules, an HLA binding peptide, the drug and the T-cell
      receptor. T-cell responses can involve drugs and stable or reactive metabolites
      bound covalently or non-covalently to any component of this complex. Recent
      research has linked the HLA associations to the disease through the
      characterization of drug-specific T-cell responses restricted to specific
      alleles. However, there is now a need to identify the additional genetic or
      environment factors that determine susceptibility and use our increased knowledge
      to develop predictive immunogenicity tests that offer benefit to Pharma
      developing new drugs.

PMID- 29460641
TI  - Novel blood glucose lowering therapies for managing type 1 diabetes in paediatric
      patients.
AB  - INTRODUCTION: Therapy for type 1 diabetes (T1D) is mainly restricted to insulin
      treatment. The management of paediatric patients with T1D should tackle not only
      glucose control, but also insulin resistance, beta-cell preservation, quality of
      life and cardiovascular disease risk factors, which are increasingly recognized
      to occur in adolescents with T1D. Areas covered: This review examines the
      recently published literature from PubMed on non-insulin agents for the
      management of T1D in paediatric patients. Expert opinion: Few paediatric patients
      with T1D are achieving their metabolic targets. Current data support the need for
      new strategies and the consideration of additional therapies that not only may
      help patients, their families and their physicians to meet HbA1c targets, but
      also may preserve residual islet mass and good quality of life and prevent
      microvascular and macrovascular complications, thereby, reducing hypoglycaemic
      episodes. Non-insulin adjunctive therapies may improve not only glucose control,
      but also insulin sensitivity, in addition to preserving beta-cell function in T1D
      patients. Thus, more studies are required to define the potential role of these
      therapies in the management of paediatric patients.

PMID- 29460642
TI  - Novel targeted therapy strategies for biliary tract cancers and hepatocellular
      carcinoma.
AB  - Worldwide hepatobiliary cancers are the second leading cause of cancer related
      death. Despite their relevance, hepatobiliary cancers have a paucity of approved
      systemic therapy options. However, there are a number of emerging therapeutic
      biomarkers and therapeutic concepts that show promise. In hepatocellular
      carcinoma, nivolumab appears particularly promising and recently received US FDA
      approval. In intrahepatic cholangiocarcinoma, therapies targeting FGFR2 and IDH1
      and immune checkpoint inhibitors are the furthest along and generating the most
      excitement. There are additional biomarkers that merit further exploration in
      hepatobiliary cancers including FGF19, ERRFI1, TERT, BAP1, BRAF, CDKN2A, tumor
      mutational burden and ERBB2 (HER2/neu). Development of new and innovative
      therapies would help address the unmet need for effective systemic therapies in
      advanced and metastatic hepatobiliary cancers.

PMID- 29460643
TI  - Para-ovarian adrenal rest tumors: gynecologic manifestations of untreated
      congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is an inherited disorder of adrenal
      steroidogenesis often diagnosed in infancy. Gynecologists may encounter adult
      patients with CAH due to the clinical effects of increased androgens, e.g.
      hirsutism, clitoromegaly, oligomenorrhea, or, rarely, pelvic masses. This case
      report reviews the association of para-ovarian adrenal rest tumors with CAH, and
      the role of gynecologists in their evaluation and treatment. A 23-year-old woman
      with CAH (21-hydroxyase deficiency) untreated for the past 5 years presented with
      a pelvic mass and elevated serum testosterone (1433 ng/dL) and plasma ACTH (1117
      pg/mL). Intraoperative findings revealed multiple retroperitoneal masses. Final
      pathology demonstrated adrenal rest tissue. Para-ovarian and ovarian adrenal rest
      tumors may present as a rare gynecologic manifestation in patients with untreated
      CAH.

PMID- 29460644
TI  - Functional Outcomes of Symptomatic Implant Removal Following Ankle Fracture Open
      Reduction and Internal Fixation.
AB  - BACKGROUND: Orthopedic implant removal following open reduction internal fixation
      of a fracture is a common procedure, especially in the foot and ankle. The
      purpose of this study was to evaluate functional change after the removal of
      symptomatic implants following ankle fracture open reduction internal fixation
      (ORIF) using the Short Musculoskeletal Function Assessment (SMFA) outcome score.
      We hypothesized that implant removal after ankle fracture would result in
      improved functional outcomes. METHODS: Retrospective review of prospectively
      collected data on patients with a closed ankle fracture between 2013 and 2016 was
      performed. Inclusion criteria were skeletal maturity, symptomatic ankle implants
      and completion of the SMFA questionnaire prior to and 6 months after removal.
      Exclusion criteria were development of a nonunion, prior or current infection,
      peripheral neuropathy or ongoing litigation surrounding the surgery. The primary
      outcome was change in SMFA score from baseline to follow-up using Wilcoxon signed
      rank test. Additional logistic regression models evaluated the effects of age,
      sex, body mass index, smoking status, and patient American Society of
      Anesthesiologists scores. RESULTS: The study population consisted of 43 patients.
      There was a statistically significant improvement in function, represented by a
      decrease in SMFA scores from baseline to the 6-month follow-up period (? = -4.1
      [95% confidence interval, -7.0, -1.3]; P = .003). Secondary outcome measures of
      the bother index and daily activities domain also demonstrated significant
      improvements ( P = .005 and P = .002, respectively). Additional logistical
      regression models identified no significant effects by assessed covariates for
      change in SMFA scores. CONCLUSION: Patients with symptomatic implants following
      ankle fracture ORIF had a statistically significant improvement in function
      following implant removal. There appears to be value in removing implants from
      the ankle in patients who report discomfort during daily activities. Further
      investigation into the specific indications for implant removal and the impact of
      injury and fracture pattern on outcomes is warranted. LEVEL OF EVIDENCE: Level
      IV, case series.

PMID- 29460645
TI  - Biomechanical Evaluation of Suture Configurations in Lesser Toe Plantar Plate
      Repairs.
AB  - BACKGROUND: Lesser toe metatarsal-phalangeal (MTP) joint instability can be a
      major source of pain and dysfunction. Instability occurs when there is
      incompetence of the plantar plate and/or collateral ligaments. Newer operative
      treatments focus on performing anatomic repairs of the plantar plate. The goal of
      this study was to compare the biomechanical properties of 3 suture configurations
      that may be used for plantar plate repairs. METHODS: Biomechanical analysis of 27
      lesser toe plantar plates from fresh frozen human cadavers was completed. The
      plantar plate was detached from the proximal phalanx, and suture was placed in
      the distal plantar plate in a horizontal mattress, luggage-tag, or Mason-Allen
      suture configuration. Cyclic loading followed by load-to-failure testing was
      performed. RESULTS: There was a significant difference in peak load-to-failure
      force between constructs (mattress: 115.53 +/- 15.95 N; luggage-tag 102.42 +/-
      19.33 N; Mason-Allen: 89.96 +/- 15.78 N; P = .015). Post hoc analysis
      demonstrated that the mattress configuration had significantly higher load-to
      failure force compared with the Mason-Allen configuration ( P = .004). There were
      no significant differences between the mattress and the luggage-tag
      configurations or the luggage-tag and the Mason-Allen configurations. There were
      no differences in construct stiffness, axial displacement at the time of failure,
      or number of cycles required to produce 2 mm of displacement. CONCLUSION: The
      mattress configuration demonstrated better peak load-to-failure force compared
      with the Mason-Allen configuration but was not statistically different from the
      luggage-tag configuration. Although not significant, the mattress configuration
      trended toward higher load-to-failure force compared with the luggage-tag.
      CLINICAL RELEVANCE: The horizontal mattress stitch may be the biomechanically
      superior configuration in plantar plate repairs.

PMID- 29460646
TI  - Sex hormone-binding globulin levels during the first trimester may predict
      gestational diabetes mellitus development.
AB  - AIM: To investigate the association of sex hormone-binding globulin (SHBG) levels
      of early pregnancy with gestational diabetes mellitus (GDM) development. METHODS:
      A total of 443 pregnant women during the first trimester (<12 weeks) were
      enrolled. SHBG levels were measured. RESULTS: SHBG level was lower in women with
      GDM than in women without GDM (93.9 +/- 34.4 nmol/l vs 128.1 +/- 60.3 nmol/l; p =
      0.001). Among the four quartiles (Q1-Q4) according to SHBG levels, GDM incidences
      were 17.5, 27.8, 5.1 and 2.6%, respectively. No differences were found between Q1
      and Q2, and Q3 and Q4. The risk of developing GDM among women in Q1 + Q2 compared
      with Q3 + Q4 was 5.7. CONCLUSION: Decreased SHBG concentrations during the first
      trimester may predict GDM development.

PMID- 29460647
TI  - Biomarkers for Sjogren's syndrome.
AB  - Sjogren's syndrome (pSS) is a complex and heterogeneous disorder characterized by
      different clinical subsets. Recently, great efforts have been made searching for
      reliable biomarkers able to ameliorate the diagnostic algorithm and the
      prognostic stratification of pSS patients and ultimately allowing the scientific
      community to address some of the unmet needs for the disease. In this review, we
      have summarized the state of the art of 'traditional' widely acknowledged
      clinical, serological and histologic biomarkers for pSS with the aim of
      highlighting their relevance and limitations in clinical practice. We have also
      explored some of the novel potential biomarkers that have been proposed more
      recently, potentially able to open new ways in the assessment of the disease.

PMID- 29460648
TI  - Telemonitoring and home hospitalization in patients with chronic obstructive
      pulmonary disease: study TELEPOC.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major consumer of
      healthcare resources, with most costs related to disease exacerbations.
      Telemonitoring of patients with COPD may help to reduce the number of
      exacerbations and/or the related costs. On the other hand, home hospitalization
      is a cost-saving alternative to inpatient hospitalization associated with
      increased comfort for patients. The results are reported regarding using
      telemonitoring and home hospitalization for the management of patients with COPD.
      METHODS: Twenty-eight patients monitored their health parameters at home for six
      months. A nurse remotely revised the collected parameters and followed the
      patients as programmed. A home care unit was dispatched to the patients' home if
      an alarm signal was detected. The outcomes were compared to historical data from
      the same patients. RESULTS: The number of COPD exacerbations during the study
      period did not reduce but the number of hospital admissions decreased by 60% and
      the number of emergency room visits by 38%. On average, costs related to
      utilization of healthcare resources were reduced by ?1,860.80 per patient per
      year. CONCLUSIONS: Telemonitoring of patients with COPD combined with home
      hospitalization may allow for a reduction in healthcare costs, although its
      usefulness in preventing exacerbations is still unclear.

PMID- 29460649
TI  - Identification of potential 'lifestyle-responsive' epigenomic biomarkers in
      healthy women aged 18-40.
AB  - CONTEXT: Human health is complex and multifaceted; there is a need for biomarkers
      that reflect the multidimensional nature of health. OBJECTIVE: To identify
      potential epigenomic biomarkers of health in women aged 18-40 participating in a
      six-month lifestyle intervention, next level health. MATERIALS AND METHODS:
      Methylation data were obtained by reduced representation bisulphite sequencing of
      21 female intervention participants as well as three non-participants. The
      Differential Methylation Analysis Package (DMAP) was used to investigate inter-
      and intra-individual variability and to identify potential targets of transient
      epigenetic control in the population studied. RESULTS: Eleven genes were
      identified as significantly differentially methylated post- intervention in all
      21 participants. 1884 genomic locations were found to be differentially
      methylated amongst the total female population studied representing potential
      epigenomic biomarkers. CONCLUSIONS: The ability to demonstrate epigenetic changes
      arising from a lifestyle intervention can provide key information on the
      relationship between gene regulation, human behaviour and health.

PMID- 29460650
TI  - A comparison of human natural monoclonal antibodies and aptamer conjugates for
      promotion of CNS remyelination: where are we now and what comes next?
AB  - INTRODUCTION: Multiple sclerosis (MS) is a chronic and progressive inflammatory
      demyelinating disease of the human central nervous system (CNS) and is the most
      common disabling neurological condition in young adults, resulting in severe
      neurological defects. No curative or long-term progression-inhibiting therapy has
      yet been developed. However, recent investigation has revealed potential
      strategies that do not merely modulate potentially pathogenic autoimmune
      responses, but stimulate remyelination within CNS lesions. Areas covered: We
      discuss the history and development of natural human IgM-isotype immunoglobulins
      (HIgMs) and recently-identified aptamer-conjugates that have been shown to
      enhance endogenous myelin repair in animal models of demyelination by acting on
      myelin-producing oligodendrocytes (OLs) or oligodendrocyte progenitor cells
      (OPCs) within CNS lesions. We also discuss future development aims and
      applications for these important novel technologies. Expert opinion: Aptamer
      conjugate Myaptavin-3064 and recombinant human IgM-isotype antibody rHIgM22
      regenerate CNS myelin, thereby reducing axonal degeneration and offering the
      potential of recovery from MS relapses, reversal of disability and prevention of
      disease progression. Advancement of these technologies into the clinic for MS
      treatment is therefore a top priority. It remains unclear to what extent the
      therapeutic modalities of remyelinating antibodies and aptamers may synergize
      with other currently-approved therapies to yield enhanced therapeutic effects.

PMID- 29460653
TI  - Risk of osteoporosis in microscopic colitis.
AB  - OBJECTIVES: Patients with microscopic colitis (MC) have several risk factors for
      osteoporosis. The prevalence of osteopenia and osteoporosis in MC is unknown. The
      primary purpose of this study was to evaluate bone mineral status in MC. METHODS:
      Patients with MC and disease activity within the last 2 years were included. Bone
      turnover markers were analyzed and bone mineral density (BMD) was measured with
      Dual Energy X-ray Absorptiometry (DXA) at inclusion and after one year. Medical
      history, demographics, risk factors for osteoporosis, disease activity and
      treatment with cumulative budesonide dosage at least 3 years before inclusion was
      registered. Adrenal function was tested by adrenocortico-tropic hormone (ACTH)
      and an ACTH stimulation test at inclusion. Results were compared with age and sex
      matched controls. RESULTS: Fifty MC patients (44 women) were included. Median age
      67 (range 45-93); median disease duration 28 month (range 2-163); median
      cumulative budesonide dosage 702 mg (range 0-5400). No difference in number of
      patients with osteoporosis or osteopenia and BMD was detected between groups. The
      bone mineral formation marker specific alkaline phosphatase was lower in MC than
      controls 12 (5-69) ug/l versus 16 (10-35) ug/l (p < 0.005). Patients more often
      smoked (34% versus 10%, p = 0.001). Disease duration and cumulative budesonide
      dose was associated with lower BMD and T-score in hip (Spearman's rho; p < 0.05)
      with a cut of point of 2500 mg budesonide predicting osteopenia. Budesonide
      treatment did not affect adrenal gland function. CONCLUSION: The risk of
      osteoporosis in patients with MC is not increased. However, DXA scan is
      recommended in MC patients with known risk factors or active disease requiring
      longstanding budesonide treatment. Supplementation of calcium and vitamin-D in
      patients treated with budesonide is recommended.

PMID- 29460654
TI  - Cumulative experience and long term follow-up of pentostatin-based
      chemoimmunotherapy trials for patients with chronic lymphocytic leukemia.
AB  - BACKGROUND: 7 regimens of pentostatin based chemoimmunotherapy (CIT) for
      progressive previously untreated CLL primarily with long term follow-up to update
      both efficacy and toxicity. RESEARCH DESIGN AND METHODS: Prognostic markers
      including assessment of IGVH and FISH status were done on all. Response rates and
      95% binomial confidence intervals were calculated for each regimen and in the
      combined cohort. Overall survival and treatment-free survival were evaluated
      using Kaplan-Meier methods. RESULTS: The initial CIT trial was pentostatin (2
      mgs/m2), cyclophosphamide (600 mg/m2) and rituximab (PCR) but subsequent P based
      CIT trials with modifications in subsequent trials. The cohort (n = 288) included
      52% with unmutated IGVH status and del17p (4.5%) and del11q (14.9%). Toxicity
      profiles were primarily hematologic and no patient has developed MDS or AML after
      a median follow-up of 6.4 years. The overall response rate across all trials was
      found to be over 90% with a 41% complete response rate. We validated that the CLL
      IPI model segregates progressive CLL patients into 4 risk groups associated with
      OS and TFS. CONCLUSIONS: The high overall and complete response levels in
      favorable genetic risk CLL along with favorable toxicity profiles provide
      rationale for consideration of a PC based strategy for previously untreated
      progressive CLL.

PMID- 29460655
TI  - Clinical evidence for washing and cleansers in acne vulgaris: a systematic
      review.
AB  - PURPOSE: Washing and over-the-counter cleansers are common interventions in acne
      vulgaris (AV), but the clinical evidence for their benefit is poorly understood.
      This systematic review presents clinical studies of washing and cleanser efficacy
      in acne vulgaris to guide treatment recommendations of dermatologists. MATERIALS
      AND METHODS: We surveyed English-language articles indexed in MEDLINE (1951-March
      2017) and EMBASE (1974-March 2017). Articles were required to be prospective
      studies of a single over-the-counter cleanser or washing intervention in AV with
      an objective AV outcome measurement published in a peer-reviewed journal. RESULTS
      AND CONCLUSIONS: Fourteen prospective studies representing 671 participants were
      included in this review. Modalities investigated included face washing frequency,
      true soap/syndet cleansing bars, antiseptic cleansers, alpha and beta-hydroxy
      (i.e. salicylic) acid cleansers, and several proprietary formulations. Given the
      low number of well-performed clinical studies of cleansers and washing, it is
      difficult to formulate reliable recommendations. We hope that our findings
      highlight the necessity of further investigation in this area.

PMID- 29460656
TI  - Are skin equipment for assessing childhood eczema any good?
AB  - AIM: Symptomatology and severity of atopic dermatitis (AD) can be objectively
      measured with equipment. This study aimed to compare skin measurements and
      investigate their correlations with various clinical severity scores. METHODS:
      Skin hydration (SH), transepidermal water loss (TEWL), pH, erythema, pigmentation
      and ITA (individual typology angle) were measured (using Delfin, Courage+Khazaka
      and Mettler Toledo equipment), and correlated with Patient-Oriented Eczema
      Measure (POEM, a short-term subjective-symptom score), Scoring Atopic Dermatitis
      (SCORAD, a short-term subjective-symptom and objective-sign score), Nottingham
      Eczema Severity Score (NESS, a long-term subjective-symptom score), Children
      Dermatology Life Quality Index (CDLQI, a short-term subjective-symptom score)
      with Spearman's rho coefficient. RESULTS: 80 sets of clinical scores from eczema
      patients (mean age: 10.8 +/-4.9years; 44.6% male) were evaluated. The POEM,
      objective SCORAD, CDLQI correlated well with each other. Skin pH ranged from 4.3
      7.0 (mean 5.7+/-0.61). Skin pH, were correlated with Objective SCORAD components,
      including area (rho= 0.269, p = 0.036), erythema (rho= 0.302, p = 0.018) and
      lichenification (rho = 0.365, p = 0.026) and with the usage frequency of topical
      antibiotics. Skin pH was also correlated with other skin measurements, including
      SH (Delfin equipment: rho=-0.38, p < 0.001). SH and TEWL as measured by Delfin
      equipment correlated better with a number of symptoms and signs than
      Courage+Khazaka equipmnt. Other clinical measurements including erythema,
      melanin, and skin colour did not demonstrate strong correlations with clinical
      symptom scores. CONCLUSION: Skin pH (using Mettler Toledo), SH and TEWL (using
      Delfin equipment) correlated well with various clinical symptomatology scores.
      Less acidic pH appears to be associated with worse clinical scores of
      symptomatology, and increase usage of topical antibiotics, These findings not
      only support the supplementary usage of equipment in aiding objective
      documentation of clinical symptomatology in eczema therapeutic research but also
      the advocacy of maintaining more acidic skin and avoiding alkaline soap and
      emollient products.

PMID- 29460657
TI  - Introductory paragraph.

PMID- 29460659
TI  - Video assisted patient education improves compliance with follow up and
      depression scores in Inflammatory Bowel Diseases.
AB  - OBJECTIVES: Patients with inflammatory bowel diseases (IBD) have to deal with a
      poor quality of life (QOL) and psychomorbidity resulting from an incurable
      illness. We aimed to study the effect of patient education on QOL, compliance,
      anxiety and depression in IBD. METHODS: Patients were prospectively enrolled over
      two years beginning July 2014 and divided into an interventional and usual care
      group. Both received the standard of care, but the former in addition received an
      8 min session of video-assisted education. Compliance to drugs was defined as
      drug intake of > 80% of the prescribed dose, and adherence to scheduled follow up
      visits were also compared. Self-administered questionnaires namely Short IBD
      questionnaire (SIBDQ), Beck Anxiety and Depression Inventory (BAI, BDI-II),
      Hospital Anxiety and Depression Scale (HADS) were used to assess QOL, anxiety and
      depression respectively at baseline, 6 months and 1 year. RESULTS: Of the 91
      patients enrolled, 84 [92.3%; male = 66 (78.57%)] completed the follow up.
      Significantly more patients were compliant to follow up visits in the
      intervention and usual care groups respectively at 6 months (88.4% versus 65.8%
      respectively; p < 0.01) and 1 year (72.1% versus 46.3% respectively; p < 0.01).
      The median (IQR) scores for HADS-Depression over 1 year were significantly better
      in the interventional group than usual care (p < 0.049). The differences in
      SIBDQ, BDI-II, BAI, HADS-Anxiety and compliance to drug therapy between the
      groups did not reach statistical significance. CONCLUSION: Video assisted patient
      education improved compliance to follow up visits and depression scores in IBD.
      Further modifications in the educational video content and delivery might improve
      compliance to drug therapy, QOL and anxiety scores.

PMID- 29460660
TI  - Early repolarization pattern in the coronary slow flow phenomenon.
AB  - BACKGROUND: The coronary slow flow phenomenon (CSFP) is well-documented, and the
      early repolarization pattern (ERP) has recently been shown to be a risk factor
      for the development of malignant ventricular arrhythmias. METHODS: Those with
      true CSFP were included as cases and those with normal angiograms were included
      as controls. We assessed J-point elevation on surface electrocardiograms (ECGs)
      and defined ERP as notching or slurring of the terminal portion of the QRS
      takeoff. RESULTS: We enrolled 115 cases (33 females, 82 males; mean age, 51.9 +/-
      11.5 years) and 45 controls (13 females, 32 males; mean age, 50.8 +/- 11.7
      years). ERP was more common among cases than among controls (65% vs. 28%, p =
      .001). Compared with the controls, cases were more likely to have J-point
      elevation in the inferior leads (25% vs. 13%, p = .002), in the D1 to aVL leads
      (22% vs. 15%, p = .001), and in the lateral leads (17.3% vs. 0%), p = .001).
      Notching was also significantly more common in cases than in controls (26.0% vs.
      2.2%, p = .0001). Finally, concave/ascendant ST segment (33.9% vs. 5.2%, p =
      .006), horizontal/non-ascendant ST segment (14.7% vs. 1.7%, p = .054), and
      horizontal/non-ascendant ST segment and notching (15.6% vs. 2.2%, p = .012)
      patterns were more common in cases than in controls. CONCLUSIONS: We report that
      CSFP is associated with J-wave and slurring ERPs. However, the clinical
      significance of these changes needs to be clarified.

PMID- 29460661
TI  - Effective environmental factors on geographical distribution of traffic accidents
      on pedestrians, downtown of Tehran City.
AB  - The aim of this study was to geographically analyse the traffic casualties in
      pedestrians in downtown of Tehran City. Study population consisted of pedestrians
      who had traffic injury accidents from April 2014 to March 2015 in Tehran City.
      Data were extracted from the offices of traffic police and municipality. For
      analysis of environmental factors and site of accidents, Ordinary Least Square
      (OLS) regression models and Geographically Weighted Regression (GWR) were used.
      All pedestrian accidents including 514 accidents were assessed in this study in
      which the site of accidents included arterial streets in 370 (71.9%) cases,
      collector streets in 133 cases (25.2%) and highways in 11 cases (2.1%).
      Geographical units of traffic accidents in pedestrians had statistically
      significant relationship with the number of bus stations, number of crossroads
      and recreational areas. Neighbourhoods close to markets are considered as the
      most dangerous places for injury in traffic accidents.

PMID- 29460662
TI  - Metabolic disposition of WTX101 (bis-choline tetrathiomolybdate) in a rat model
      of Wilson disease.
AB  - 1. WTX101 (bis-choline tetrathiomolybdate) is an investigational copper (Cu)
      protein-binding agent developed for the treatment of Wilson disease (WD), a rare
      genetic disorder caused by mutations in the ATP7B Cu-transporter and resulting in
      toxic Cu accumulation. 2. Mass balance of a single intravenous WTX101 dose,
      measured as molybdenum (Mo), was assessed over 168 h in control (Long Evans
      Agouti [LEA]) and Long-Evans Cinnamon (LEC) rats, a WD model. 3. In LEC rats, Mo
      was partially excreted (up to 45%); 29% by renal clearance, and faecal clearance,
      still ongoing at 168 h, accounted for 16%. In contrast, in LEA rats, Mo was
      almost fully excreted (~87%); 79% was renally cleared with only 7% faecal
      excretion. 4. In LEC rats, the proportion of faecal to renal Mo excretion was
      enhanced (4:6) compared to controls (1:9). 5. Substantially more Mo was found in
      LEC liver and kidney compared with LEA tissues, in line with tissue Cu
      distribution. 6. These findings are consistent with the WTX101 mechanism of
      action: in the WD model, excess Cu is removed from hepatic metallothionein and
      retained within the stable tetrathiomolybdate-Cu-albumin tripartite complex,
      preventing tetrathiomolybdate degradation and resulting in less urinary
      elimination and greater faecal excretion than in controls.

PMID- 29460663
TI  - Response to Dr. Bernard D. Goldstein's Letter to the Editor.

PMID- 29460664
TI  - Tubulin diversity and neuronal migration.

PMID- 29460665
TI  - Under the British Roof: The British Contribution to the Development of Hospice
      and Palliative Care in Poland.
AB  - The article focuses on British contribution to the development of palliative and
      hospice care in Poland in the 1980s and beyond. It is based on archival research
      in the hospices in Cracow and Poznan and broad-scoped Polish journals' review.
      The social background of the hospice movement in Poland is described. We explore
      the role of inspiration and help of Dame Cicely Saunders and other British
      leaders in the transfer of British hospice philosophy and practice of palliative
      care to the medical community in Poland. This study demonstrates the importance
      of institutions for the formal exchange of medical information.

PMID- 29460666
TI  - Effects of Common Ear Drops on Tympanic Membrane Healing in Rats.
AB  - Objective Ciprofloxacin + dexamethasone ear drops have been associated with
      higher rates of tympanic membrane perforations than ofloxacin. This was thought
      to be an effect of the steroid; however, ciprofloxacin (sans steroid) has been
      found to be more toxic to tympanic membrane fibroblasts than ofloxacin in vitro.
      This study aimed to compare the effect of these agents on tympanic membrane
      healing in vivo. Study Design Controlled animal study. Setting Academic research
      laboratory. Methods Perforations were created in 54 rats with a carbon dioxide
      laser. Rats were randomized to 6 groups (9/group), with 1 ear receiving
      ofloxacin, ciprofloxacin, dexamethasone, ofloxacin + dexamethasone, ciprofloxacin
      + dexamethasone, or neomycin, and the contralateral ear receiving saline twice
      daily for 10 days. Healing was assessed over 40 days. Results Ofloxacin did not
      delay healing relative to saline. All other treatments delayed healing relative
      to ofloxacin at day 10 ( P < .0001). Dexamethasone and ofloxacin + dexamethasone
      delayed healing up to day 14 ( P < .0001). Neomycin and ciprofloxacin +
      dexamethasone further delayed healing up to day 28 ( P = .009) and day 35 ( P =
      .043), respectively. All eardrums healed by day 10 with ofloxacin, day 20 with
      ciprofloxacin, day 28 for dexamethasone, and day 35 for ofloxacin +
      dexamethasone. At day 40, 2 of 9 ciprofloxacin + dexamethasone-treated eardrums
      had not healed. All saline-treated eardrums in the ofloxacin, ciprofloxacin,
      dexamethasone, and ofloxacin + dexamethasone groups were healed by day 14, but
      this was delayed to day 20 in the ciprofloxacin + dexamethasone group ( P =
      .007). Conclusions Ototopical quinolones delay rat tympanic membrane healing in a
      drug-specific manner, with ciprofloxacin having a greater impact than ofloxacin.
      This effect is potentiated by steroids.

PMID- 29460667
TI  - Call From Solidarity Academies.

PMID- 29460668
TI  - Personal Control Over Decisions to Participate in Research by Persons With
      Histories of Both Substance Use Disorders and Criminal Justice Supervision.
AB  - Individuals must feel free to exert personal control over decisions regarding
      research participation. We present an examination of participants' perceived
      personal control over, as well as reported pressures and threats from others,
      influencing their decision to join a study assessing the effectiveness of
      extended-release naltrexone in preventing opioid dependence relapse. Most
      participants endorsed a strong sense of control over the decision; few reported
      pressures or threats. Although few in number, participants' brief narrative
      descriptions of the pressures and threats are illuminating and provide context
      for their perceptions of personal control. Based on this work, we propose a
      useful set of tools to help ascertain participants' sense of personal control in
      joining research.

PMID- 29460669
TI  - Treatment Times in Salivary Gland Cancer: National Patterns and Association with
      Survival.
AB  - Objective To characterize treatment times in salivary cancer; associate treatment
      times with patient, tumor, and treatment characteristics; and examine the
      association of treatment times and overall survival. Study Design Retrospective
      cohort. Setting Commission-on-Cancer Accredited Hospitals 2004-2013. Subjects and
      Methods In total, 5953 patients with salivary cancer included in the National
      Cancer Database were identified. For each treatment interval, patients in the
      fourth quartile ("prolonged") were compared to patients in the first and second
      quartiles ("not prolonged"). Patient, tumor, and treatment characteristics were
      associated with prolonged times via multivariable binary logistic regression.
      Prolongation of each interval was associated with overall survival via
      multivariable Cox proportional hazards regression, controlling for clinically
      relevant factors. Results Median durations for diagnosis-to-treatment initiation,
      surgery-to-radiation treatment (RT), RT duration, total treatment package, and
      diagnosis-to-treatment end were 31, 44, 47, 92, and 110 days, respectively. Race,
      insurance status, comorbidities, age, T and N stage, facility volume and
      location, and a facility care transition from diagnosis to initial treatment were
      associated with prolonged treatment time. Prolonged RT duration was associated
      with decreased overall survival (OS) (62% vs 75% 5-year OS, HR = 1.26 [95%
      confidence interval (CI), 1.09-1.47]; P = .002), but prolonged diagnosis-to
      treatment initiation, surgery-to-RT, total treatment package, and diagnosis-to
      treatment end intervals were not (70% vs 67% 5-year OS, HR = 1.11 [95% CI, 0.92
      1.34], P = .284; 72% vs 68%, HR = 0.93 [95% CI, 0.79-1.09], P = .370; 70% vs 70%,
      HR = 1.00 [95% CI, 0.84-1.20], P = .974; 66% vs 71%, HR = 0.99 [95% CI, 0.84
      1.18], P = .920, respectively). Conclusion The median durations identified here
      can serve as reference points. Radiation therapy duration is associated with
      overall survival in salivary cancer and could be considered a quality indicator.

PMID- 29460670
TI  - Opioid Prescribing Patterns among Otolaryngologists.
AB  - Objectives To evaluate national trends in opioid prescribing patterns by
      otolaryngologists for postoperative pain control after common otolaryngologic
      procedures. Study Design Cross-sectional; survey. Subjects and Methods A survey
      to determine opioid prescribing patterns for the treatment of postoperative pain
      following common otolaryngologic procedures was distributed to all members of the
      American Academy of Otolaryngology-Head and Neck Surgery. Results The most common
      pain medication prescribed for adults postoperatively was hydrocodone
      acetaminophen (73%), followed by oxycodone-acetaminophen (39%). The most common
      pain medication prescribed postoperatively for children was acetaminophen (67%),
      followed by nonsteroidal anti-inflammatory drugs (65%). Overall, there was a wide
      variation in quantity of opioids prescribed for each surgery, ranging from 0 to
      more than 60 doses. Mean opioid prescriptions were greatest for tonsillectomy (37
      tablets) and least for direct laryngoscopy (5.3 tablets). Conclusion This study
      identifies nationwide variations in opioid prescribing patterns among
      otolaryngologists. While otolaryngology is a relatively small specialty, we still
      have an obligation to work with all physicians to help combat the current opioid
      epidemic. By evaluating nationwide postoperative pain regimens, we are moving
      closer toward understanding how to reduce the opioid burden.

PMID- 29460671
TI  - Targeted delivery of miRNA-204-5p by PEGylated polymer nanoparticles for colon
      cancer therapy.
AB  - AIM: miRNAs have been recognized for their potential in cancer therapeutics, and
      multiple miRNAs were suggested to affect target genes expression. To overcome
      limitations of free synthetic miRNAs, such as easily degraded in biofluids and
      limited in cellular uptake, novel miRNAs delivery systems need to be developed.
      MATERIALS & METHODS: Using surface-functionalizing technique, poly(D,L-lactide-co
      glycolide)/poly(L-lactide)-block-poly(ethylene glycol)-folate polymer
      nanoparticle (PLGA/PLA-PEG-FA) loaded with miR-204-5p (FA-NPs-miR-204) was
      developed. The therapeutic efficacy of FA-NPs-miR-204 was evaluated in the Luc-HT
      29 xenograft tumor model in vivo. RESULTS: FA-NPs-miR-204 could be taken up by HT
      29  and HCT-116 cells efficiently, resulting in significant inhibitory effect on
      cell proliferation and promotive effect on cell apoptosis. In vivo study showed
      that FA-NPs-miR-204 could exert tumor suppressive function in Luc-HT-29 xenograft
      model. CONCLUSION: Our study demonstrates a convenient miRNA delivery system that
      targets tumor tissue and exerts tumor suppressive function, thus demonstrating a
      potential new therapeutic option for colon cancer.

PMID- 29460672
TI  - Effects of distance and rescue time to medical facilities on traffic mortality
      utilizing GIS.
AB  - Although supported by little scientific evidence, the concept of 'golden hour,'
      which claims that mortality for trauma patients rises significantly over rescue
      time, plays a vital role in the design of our current trauma system. Only the
      contrary results could be found by using Fatality Analysis Reporting System data
      from 2010 to 2012. The results of logistic regression showed that longer total
      time intervals were associated with lower traffic mortality, with an odds ratio
      (OR) of 0.993 per minute. Utilizing the closest facility solver in the Geographic
      Information System, the effect of 'reverse causation' and the difference between
      trauma centre and non-trauma centre on the time-mortality relationship were
      discussed. Furthermore, based on the Kentucky Collision Analysis for the Public
      data from 2010 to 2012, the results of logistic regression showed that the
      mortality increased with each additional mile to the trauma centre with an OR of
      1.011 per mile.

PMID- 29460673
TI  - Religion, Religious Heterogeneity, and Intimate Partner Violence Among Korean
      Immigrant Women.
AB  - This study examined the role of religious affiliations and frequency of religious
      service attendance-such as church, Bible studies, and temples-as well as
      religious heterogeneity between couples on intimate partner violence (IPV) among
      Korean immigrant women in the United States. Through a case-control design, this
      study compared 64 Korean immigrant IPV victims with 63 Korean immigrant non-IPV
      victims. This study's findings reveal that for Korean immigrant women, a high
      frequency of religious service attendance was associated with higher IPV
      victimization, while their partners' high religious service attendance was
      associated with lower IPV victimization. When women's partners were religious
      compared with when they were not religious, they were less likely to perpetrate
      IPV even when the partners' alcohol consumption frequency increased. Also, when
      there was a gap between couples regarding frequency of religious attendance, IPV
      victimization increased. This discussion concludes by suggesting some policy
      implications based on these findings.

PMID- 29460674
TI  - Exploring Reproductive Coercion in Relationship Contexts Among Young Adult,
      Primarily African American Women at Three Women's Health Clinics.
AB  - Understanding reproductive coercion experiences in marginalized populations is
      important to assist in tailoring care and services. Reproductive coercion is
      consistently associated with intimate partner violence (IPV), engaging in sexual
      risk-taking, and is more commonly reported among non-White women. We conducted a
      secondary analysis of data from a mixed methods study to examine reproductive
      coercion in relationship contexts among a sample ( N = 130) of young adult,
      primarily African American women recruited from three women's health clinics; 12
      also participated in an in-depth interview. Thirty-six women (27.7%) reported
      reproductive coercion in the past year. Past-year reproductive coercion was
      associated with relationship trust, ( t(128) = -3.01, p = .003), and past-year
      IPV (Fisher's exact test, p = .005). In the best-fit model, odds of past-year
      reproductive coercion increased by 4% with each one-point increase in
      relationship trust score (indicating reproductive coercion increased with lower
      trust; adjusted odds ratio [AOR] = 1.04; 95% confidence interval [CI] = [1.00,
      1.08]), and by more than 4 times with past experience of IPV (AOR = 4.74; 95% CI
      = [1.07, 20.86]). Qualitative analysis revealed women's awareness of reproductive
      coercion whether or not they personally experienced it. Those who experienced
      reproductive coercion identified it as a form of abuse and additionally described
      experiences of pressure to conceive from the partner's family. Our results
      support routine screening for IPV and reproductive coercion. Furthermore, the
      intersection of partner reproductive coercion with family pressure related to
      reproductive decision making should be explored to better inform clinical
      interventions.

PMID- 29460675
TI  - Risk Stratification for Postoperative Venous Thromboembolism after Endoscopic
      Sinus Surgery.
AB  - Objectives Venous thromboembolism (VTE) contributes to significant patient
      morbidity, yet the incidence of VTE following endoscopic sinus surgery (ESS) is
      unknown. Quality improvement criteria are prompting increased standardization of
      perioperative VTE prophylaxis. Risk stratification for VTE may better define best
      practice measures to balance limiting VTE development with avoiding unnecessary
      chemoprophylaxis. Study Design Retrospective cohort study. Setting Tertiary
      institution. Subjects and Methods Adult patients who underwent ESS without
      perioperative chemoprophylaxis from 2008 to 2016 were evaluated. Identification
      of VTE was performed via screening diagnosis and procedure codes and clinical
      records, with subsequent confirmation of true-positive VTE. Data for individual
      Caprini scores were abstracted from electronic medical records. The primary
      outcome was development of VTE within 30 days following ESS relative to the
      Caprini score. Results A total of 2369 ESS cases were evaluated. While initial
      screening identified multiple potential VTE events, in-depth medical record
      review confirmed only 4 true VTE (0.17%). The VTE rate among cases with a Caprini
      score of <8 (0.09%, 2/2278) was significantly less ( P = .008) than the rate with
      a score of >=8 (2.2%, 2/91). Beyond overall score, specific risk factors
      associated with development of postoperative VTE included stroke, central venous
      access, sepsis, and inpatient status (all P < .025), while prior VTE and
      hypercoagulability were not associated with postoperative VTE (all P > .5).
      Conclusions In the absence of perioperative chemoprophylaxis, postoperative VTE
      following ESS is extremely rare, particularly for patients carrying low-to
      moderate Caprini scores. Risk stratification based on these data can assist in
      the design of VTE prophylaxis guidelines for ESS patients.

PMID- 29460677
TI  - Regulation of Hydroxycinnamic Acid Degradation Drives Agrobacterium fabrum
      Lifestyles.
AB  - Regulatory factors are key components for the transition between different
      lifestyles to ensure rapid and appropriate gene expression upon perceiving
      environmental cues. Agrobacterium fabrum C58 (formerly called A. tumefaciens C58)
      has two contrasting lifestyles: it can interact with plants as either a
      rhizosphere inhabitant (rhizospheric lifestyle) or a pathogen that creates its
      own ecological niche in a plant tumor via its tumor-inducing plasmid (pathogenic
      lifestyle). Hydroxycinnamic acids are known to play an important role in the
      pathogenic lifestyle of Agrobacterium spp. but can be degraded in A. fabrum
      species. We investigated the molecular and ecological mechanisms involved in the
      regulation of A. fabrum species-specific genes responsible for hydroxycinnamic
      acid degradation. We characterized the effectors (feruloyl-CoA and p-coumaroyl
      CoA) and the DNA targets of the MarR transcriptional repressor, which we named
      HcaR, which regulates hydroxycinnamic acid degradation. Using an hcaR-deleted
      strain, we further revealed that hydroxycinnamic acid degradation interfere with
      virulence gene expression. The HcaR deletion mutant shows a contrasting
      competitive colonization ability, being less abundant than the wild-type strain
      in tumors but more abundant in the rhizosphere. This supports the view that A.
      fabrum C58 HcaR regulation through ferulic and p-coumaric acid perception is
      important for the transition between lifestyles.

PMID- 29460678
TI  - A Systematic Review of the Association between Cigarette Smoke Exposure and
      Chronic Rhinosinusitis.
AB  - Objectives Cigarette smoking and passive smoke exposure have been associated with
      chronic rhinosinusitis (CRS). Our goal in this systematic review was to (1)
      determine if there was a strong correlative effect in large population studies
      between cigarette smoke exposure and the prevalence of CRS, (2) investigate
      pathogenic mechanisms of cigarette smoke in the upper airway, and (3) determine
      if a history of cigarette smoking affects the medical and surgical outcomes of
      CRS. Data Sources MEDLINE, Embase, Cochrane CENTRAL, Web of Science SCI and CPCI
      S, and websites. Methods A comprehensive literature review and quantitative meta
      analysis of studies based on the PRISMA protocol and examining the relationship
      between cigarette smoke exposure and CRS was performed. A search strategy was
      developed using various terms such as sinusitis, rhinitis, rhinosinusitis, and
      smoking. The articles were categorized by (1) epidemiology, (2) pathophysiology,
      and (3) outcomes. Data regarding study design, population/setting, methods, and
      bias were collected. Results The initial search generated 2621 titles/abstracts
      with 309 articles undergoing secondary review and 112 articles for final review.
      We determined that there is a strong correlation between active and passive
      cigarette smoke with the prevalence of CRS. Cigarette smoke challenge to
      sinonasal epithelia results in the release of inflammatory mediators and altered
      ciliary beat frequency. Pediatric patients exposed to secondhand smoke appear to
      have particularly poor outcomes. Conclusion There is clear evidence that
      cigarette smoke is related to CRS, but longitudinal and mechanistic studies are
      required to determine a causative effect. This information is critical for
      greater understanding of CRS health outcomes.

PMID- 29460676
TI  - Pattern-Triggered Immunity Alters the Transcriptional Regulation of Virulence
      Associated Genes and Induces the Sulfur Starvation Response in Pseudomonas
      syringae pv. tomato DC3000.
AB  - Pattern-triggered immunity (PTI) can confer broad defense against diverse
      microbes and pathogens with disparate lifestyles through the detection of
      microbial extracellular signatures by surface-exposed pattern recognition
      receptors. However, unlike recognition of pathogen effectors by cytosolic
      resistance proteins, PTI is typically not associated with a host-cell programmed
      cell death response. Although host PTI signaling has been extensively studied,
      the mechanisms by which it restricts microbial colonization are poorly
      understood. We sought to gain insight into the mechanisms of PTI action by using
      bacterial transcriptomics analysis during exposure to PTI. Here, we describe a
      method for bacterial cell extraction from inoculated leaves that was used to
      analyze a time course of genome-wide transcriptional responses in the pathogen
      Pseudomonas syringae pv. tomato DC3000 during early naive host infection and
      exposure to pre-induced PTI in Arabidopsis thaliana. Our analysis revealed early
      transcriptional regulation of important bacterial metabolic processes and host
      interaction pathways. We observed peak induction of P. syringae virulence genes
      at 3 h postinoculation and that exposure to PTI was associated with significant
      reductions in the expression of virulence genes. We also observed the induction
      of P. syringae sulfur starvation response genes such as sulfate and sulfonate
      importers only during exposure to PTI.

PMID- 29460679
TI  - AMCP Partnership Forum: Improving Quality, Value, and Outcomes with Patient
      Reported Outcomes.
AB  - : Patient-reported outcomes (PROs), which provide a direct measure of a patient's
      health status or treatment preferences, represent a key component of the shift
      toward patient-centered health care. PROs can measure the state of a patient's
      disease-specific and overall health throughout the care continuum, enabling them
      to have a variety of uses for key health care stakeholders. Currently, PROs are
      used in drug development, aligning patient and clinician goals in care, quality
      of-care measures, and coverage and reimbursement decisions. While there have been
      significant strides by key health care stakeholders to further the development
      and use of PROs, there are a number of challenges limiting more widespread use.
      In light of these current challenges and the potential for PROs to improve health
      care quality and value, on October 19, 2017, the Academy of Managed Care Pharmacy
      convened a forum of key stakeholders representing patients, payers, providers,
      government, and pharmaceutical companies to discuss and identify solutions to the
      current challenges and barriers to further use of PROs. These discussions
      informed the development of participants' ideal future state in which PROs
      maximize the goals of all health care stakeholders and the actionable steps
      required to make the future state a reality. While stakeholders shared unique
      perspectives throughout the forum, they had consensus on 2 overarching issues:
      the importance of PROs in defining value, improving patient care, and
      implementing value-based payment models and the need for strong organizational
      and operational systems to achieve optimal adoption and use. Participants
      identified several key challenges in PRO use and adoption: achieving a
      representative patient population, inclusion of PRO data in medication labels,
      the necessity for both standardized and customizable PROs, and operational and
      organizational barriers to collecting and analyzing PROs. To overcome these
      challenges, participants recommended that manufacturers should engage key
      stakeholders early and throughout the drug development process to ensure the most
      valid and representative PROs and patient populations will be included. To
      streamline the PRO collection process, participants suggested engaging
      pharmacists and other providers who may have more frequent interaction with
      patients. Participants also recommended that PRO collection and analysis should
      use common technology platforms, streamline components of clinician care to
      reduce workflow, and be integrated with claims data to provider payers a better
      understanding of patient health in real time. Finally, additional work should be
      done to develop patient-reported outcome measures that contain relevant measures
      for all healthcare stakeholders. While significant challenges remain in PRO
      development and adoption, participants agreed that greater use can only be
      achieved through collaboration and patient-centered care. DISCLOSURES: The AMCP
      Partnership Forum titled "Improving Quality, Value, and Outcomes with Patient
      Reported Outcomes" and the development of this proceedings report were supported
      by Amgen, Boehringer Ingelheim Pharmaceuticals, Genentech, GlaxoSmithKline,
      Novartis Pharmaceuticals, Novo Nordisk, Precision for Value, Premier, Sanofi,
      Takeda Pharmaceuticals USA, and Xcenda.

PMID- 29460680
TI  - Effect of Piecemeal vs En Bloc Approaches to the Lateral Temporal Bone on
      Survival Outcomes.
AB  - Objectives Lateral temporal bone resection (LTBR) has traditionally been
      performed en bloc in accordance with oncologic principles. Occasionally, this is
      not possible due to a low tegmen or lateralized vasculature. We sought to
      determine if outcomes of piecemeal and en bloc LTBR are comparable. Study Design
      Retrospective review. Setting Two academic medical centers. Subjects and Methods
      Multi-institutional retrospective cohort study. Current Procedural Terminology
      codes were used to identify patients with T1 to T3 squamous cell carcinoma of the
      external auditory canal (EAC) who underwent LTBR from 2005 to 2015. Kaplan-Meier
      curves were constructed to compare total survival between the 2 treatment
      approaches. Pairwise comparisons were performed using chi2 and Fisher exact tests
      (significance at P = .05), as appropriate. Results Twenty-five patients were
      identified. Ten patients underwent en bloc LTBR; 15 underwent piecemeal LTBR.
      Median follow-up time was 11 months (range, 1-60 months). There was not a
      significant difference in overall survival between en bloc (38.9 months; 95%
      confidence interval [CI], 22.7-55.2) compared to piecemeal (37.5 months; 95% CI,
      21.1-53.9) procedures ( P = .519). Estimates of disease-free survival also did
      not reveal statistically significant differences: estimated mean disease-free
      survival was 48.1 months (95% CI, 33.7-62.6) in en bloc patients and 32.5 months
      (95% CI, 17.1-47.8) in piecemeal patients ( P = .246). Conclusion These data
      suggest that piecemeal resection can be considered for cases of squamous cell
      carcinoma involving the external auditory canal where anatomic constraints
      preclude a safe en bloc resection. Larger studies or studies with a longer follow
      up time may provide improved insight into survival comparisons.

PMID- 29460681
TI  - Assessment of Disease-Specific and General Patient-Reported Outcome Measures of
      Hearing Health.
AB  - Objective To assess disease-specific (Inner EAR) and general (Patient-Reported
      Outcomes Measurement Information System [PROMIS]) health status in patients
      reporting hearing loss and whether there is enough correlation between scales
      such that the general instrument alone could suffice. Study Design Correlation
      analysis of prospective cohort data. Setting Tertiary care academic medical
      center. Methods Adults presenting with a chief complaint of hearing loss
      completed the Inner EAR scale and the PROMIS instrument. Summary statistics,
      including means, percentiles, and measures of variance, were calculated. The
      Spearman rho statistic was used to test the null hypothesis that there were no
      correlations between the Inner EAR composite or global score and PROMIS scores.
      Results The mean Inner EAR composite score was 35.6, while the global item had a
      mean score of 4.8. Mean PROMIS-10 scores were 16.0 for physical health and 15.3
      for mental health. The global item and social item had mean scores of 3.6 and
      3.8, respectively. Inner EAR composite scores were significantly correlated with
      the PROMIS mental health summary scores (Spearman rho = 0.3, P = .0066) and the
      PROMIS social item score (Spearman rho = 0.4, P = .0005). The Inner EAR global
      item was moderately correlated with the PROMIS social item score (Spearman rho =
      0.3, P = .0118), while there was no significant correlation between the Inner EAR
      global item and the PROMIS physical health, mental health, or global item scores.
      Conclusions Inner EAR and a subset of PROMIS scores have weak to moderate
      correlations. Disease-specific assessment still confers independent value.

PMID- 29460682
TI  - Match 2017: Blindsided or Fumbled?
AB  - The field of otolaryngology has historically enjoyed extreme interest among
      residency applicants. However, in the past few years, the number of applicants
      has precipitously dropped, so that there is no longer a significant excess of
      applications. It remains important for academic programs to promote student
      interest in otolaryngology, to break down barriers that may dissuade excellent
      candidates, and to widen the welcome.

PMID- 29460683
TI  - Writing abilities and the role of working memory in children with symptoms of
      attention deficit and hyperactivity disorder.
AB  - The writing abilities of children with ADHD symptoms were examined in a simple
      dictation task, and then in two conditions with concurrent verbal or visuospatial
      working memory (WM) loads. The children with ADHD symptoms generally made more
      spelling mistakes than controls, and the concurrent loads impaired their
      performance, but with partly different effects. The concurrent verbal WM task
      prompted an increase in the phonological errors, while the concurrent
      visuospatial WM task prompted more non-phonological errors, matching the Italian
      phonology, but not the Italian orthography. In the ADHD group, the children
      proving better able to cope with a concurrent verbal WM load had a better
      spelling performance too. The ADHD and control groups had a similar handwriting
      speed, but the former group's writing quality was poorer. Our results suggest
      that WM supports writing skills, and that children with ADHD symptoms have
      general writing difficulties, but strength in coping with concurrent verbal
      information may support their spelling performance.

PMID- 29460685
TI  - Prognostic Value of Lymph Node Yield and Density in Head and Neck Malignancies.
AB  - Objective Studies have suggested that the lymph node yield and lymph node density
      from selective or elective neck dissections are predictive of patient outcomes
      and may be used for patient counseling, treatment planning, or quality
      measurement. Our objective was to systematically review the literature and
      conduct a meta-analysis of studies that investigated the prognostic significance
      of lymph node yield and/or lymph node density after neck dissection for patients
      with head and neck cancer. Data Sources The Ovid/Medline, Ovid/Embase, and NLM
      PubMed databases were systematically searched on January 23, 2017, for articles
      published between January 1, 1946, and January 23, 2017. Review Methods We
      reviewed English-language original research that included survival analysis of
      patients undergoing neck dissection for a head and neck malignancy stratified by
      lymph node yield and/or lymph node density. Study data were extracted by 2
      independent researchers (S.C. and M.O.). We utilized the DerSimonian and Laird
      random effects model to account for heterogeneity of studies. Results Our search
      yielded 350 nonduplicate articles, with 23 studies included in the final
      synthesis. Pooled results demonstrated that increased lymph node yield was
      associated with a significant improvement in survival (hazard ratio, 0.833; 95%
      CI, 0.790-0.879). Additionally, we found that increased lymph node density was
      associated with poorer survival (hazard ratio, 1.916; 95% CI, 1.637-2.241).
      Conclusions Increased nodal yield portends improved outcomes and may be a
      valuable quality indicator for neck dissections, while increased lymph node
      density is associated with diminished survival and may be used for postsurgical
      counseling and planning for adjuvant therapy.

PMID- 29460684
TI  - A negative feedback regulation of MTORC1 activity by the lysosomal Ca2+ channel
      MCOLN1 (mucolipin 1) using a CALM (calmodulin)-dependent mechanism.
AB  - Macroautophagy/autophagy is an evolutionarily conserved pathway that is required
      for cellular homeostasis, growth and survival. The lysosome plays an essential
      role in autophagy regulation. For example, the activity of MTORC1, a master
      regulator of autophagy, is regulated by nutrients within the lysosome. Starvation
      inhibits MTORC1 causing autophagy induction. Given that MTORC1 is critical for
      protein synthesis and cellular homeostasis, a feedback regulatory mechanism must
      exist to restore MTORC1 during starvation. However, the molecular mechanism
      underlying this feedback regulation is unclear. In this study, we report that
      starvation activates the lysosomal Ca2+ release channel MCOLN1 (mucolipin 1) by
      relieving MTORC1's inhibition of the channel. Activated MCOLN1 in turn
      facilitates MTORC1 activity that requires CALM (calmodulin). Moreover, both
      MCOLN1 and CALM are necessary for MTORC1 reactivation during prolonged
      starvation. Our data suggest that lysosomal Ca2+ signaling is an essential
      component of the canonical MTORC1-dependent autophagy pathway and MCOLN1 provides
      a negative feedback regulation of MTORC1 to prevent excessive loss of MTORC1
      function during starvation. The feedback regulation may be important for
      maintaining cellular homeostasis during starvation, as well as many other
      stressful or disease conditions.

PMID- 29460686
TI  - Anatomical Pathology of the Umbilical Cord and Its Maternal and Fetal Clinical
      Associations in 434 Newborns.
AB  - Introduction Umbilical cord (UC) abnormalities and their clinical relations in
      434 newborns were analyzed. We had previously reported on clinical associations
      of long and short UCs with any kind of malformation. This study focuses on other
      UC features (insertion, vessels, entanglements, coiling, and knots) and their
      associations with clinical characteristics and neonatal prognosis. Methods An
      observational analytic study was performed on placentas from consecutive
      deliveries. Ordered logistic regression with bivariate and multivariate analysis
      was performed to evaluate the relationship between variables of interest
      concerning UC abnormalities. Results A total of 434 placentas made up the study.
      UC abnormalities were abnormal insertion, 82 (18.86%); coiling (hypo and
      hypercoiled), 177 (40.78%); single umbilical artery (SUA), 4 (0.92%);
      entanglements, 8 (1.84%); true knots, 3 (0.69%); webs in UC base, 9 (2.07%); and
      right twist, 68 (15.67%). After analyzing maternal and fetal complications during
      pregnancy, multivariate analysis confirmed the recognized association between
      malformations and SUA and male gender; further confirmation was also made between
      hypertensive disorders of pregnancy and true knots. Discussion UC abnormalities
      associated with undesirable outcomes are varied and should be recognized and
      described. Clinical factors associated with anatomical UC abnormalities are not
      completely understood and justify forthcoming studies.

PMID- 29460687
TI  - Is Graphology Useful in Assessing Major Depression?
AB  - This study aimed to develop a handwriting analysis protocol for assessing severe
      major depressive disorder, in order to evaluate whether graphological analysis
      could be considered an objective tool and hence if it could be useful for
      clinicians in their early diagnosis. We modified and improved the methodology
      described by Lorusso et al. by proposing different graphic indexes based both on
      the literature and on the observation of a preliminary sample of 13 handwritings
      of patients affected by major depressive disorder. Then, we recruited 80
      participants, divided into two groups: clinical sample ( n = 44) and control
      group ( n = 36). We used Cohen's Kappa to evaluate the reliability of agreement
      among four professional graphologists and the consensus between the psychiatric
      assessment and the ratings given by the judges. We found satisfactory results.
      Using our protocol, we obtained higher values for Cohen's Kappa as compared with
      Lorusso et al. The agreement among graphologists is K = .62, while the K values
      for the agreement between psychiatric assessment and graphologists range between
      .47 and .60. The substantial improvements obtained in comparison with Lorusso et
      al. are encouraging and support further attempts.

PMID- 29460688
TI  - Flourishing-at-Work: The Role of Positive Organizational Practices.
AB  - The first aim of the study was to investigate the effects of flourishing at work
      (as measured by the Flourishing-at-Work Scale-Short Form) on intention to leave,
      performance, and organizational citizenship behavior. The second aim was to
      determine the prevalence of workplace flourishing and to examine differences in
      the perceived flourishing levels of teachers based on the positive practices they
      experience in their organization. A sample of 258 secondary school educators in
      the Gauteng province of South Africa was used in the cross-sectional design. The
      Flourishing-at-Work Scale-Short Form, Turnover Intention Scale, In-Role Behavior
      Scale, Organizational Citizenship Behavior Scale, and the Positive Practices
      Questionnaire were administered. The results showed acceptable psychometric
      properties for the short scale which measures flourishing. Workplace flourishing
      negatively predicted intention to leave, while positively predicting in-role
      performance and organizational citizenship behavior. A total of 44.19% of the
      population flourished, while 49.22% were moderately mentally healthy and 6.59%
      languished. Positive organizational practices were associated with flourishing at
      work.

PMID- 29460689
TI  - Exploring Characteristics and Health Care Utilization Trends Among Individuals
      Who Fall in the Health Insurance Assistance Gap in a Medicaid Nonexpansion State.
AB  - States that did not expand Medicaid under the Affordable Care Act (ACA) in the
      United States have seen a growth in the number of individuals who fall in the
      assistance gap, defined as having incomes above the Medicaid eligibility limit
      (>=44% of the federal poverty level) but below the lower limit (<100%) to be
      eligible for tax credits for premium subsidies or cost-sharing reductions in the
      marketplace. The purpose of this article is to present findings from a secondary
      data analysis examining the characteristics of those who fell in the assistance
      gap ( n = 166) in Missouri, a Medicaid nonexpansion state, by comparing them with
      those who did not fall in the assistance gap ( n = 157). Participants completed
      online demographic questionnaires and self-reported measures of health and
      insurance status, health literacy, numeracy, and health insurance literacy. A
      select group completed a 1-year follow-up survey about health insurance
      enrollment and health care utilization. Compared with the nonassistance gap
      group, individuals in the assistance gap were more likely to have lower levels of
      education, have at least one chronic condition, be uninsured at baseline, and be
      seeking health care coverage for additional dependents. Individuals in the
      assistance gap had significantly lower annual incomes and higher annual premiums
      when compared with the nonassistance gap group and were less likely to be insured
      through the marketplace or other private insurance at the 1-year follow-up.
      Findings provide several practice and policy implications for expanding health
      insurance coverage, reducing costs, and improving access to care for underserved
      populations.

PMID- 29460690
TI  - Improving mental health knowledge of the Charedi Orthodox Jewish Community in
      North London: A partnership project.
AB  - INTRODUCTION: This article describes a successful community-based partnership
      project between statutory and third-sector services targeting the strictly
      Orthodox Jewish community (OJC). METHODS: The City and Hackney Black and Minority
      Ethnic (BME) Access Service (East London NHS Foundation Trust (ELFT))
      collaborated with Bikur Cholim, a local third-sector organisation based in the
      heart of a north London Charedi OJC, to develop a brief culturally tailored
      psychoeducational group intervention focusing on mental health promotion and
      prevention. In total, 34 carers in the Charedi OJC were provided with general
      information on mental health, the availability of support services and self-care.
      RESULTS: Overall improvements in well-being, increased intentions to access
      services, particularly talking therapies, and qualitative feedback indicated that
      the group was very well received. CONCLUSION: The project endorses the value of
      culturally relevant psychoeducation, enabling suggestions for culturally
      appropriate service development.

PMID- 29460691
TI  - A New Needle Holder Design to Facilitate Intracorporeal Knot Tying.
AB  - PURPOSE: Intracorporeal knot tying in laparoscopic surgery continues to be a
      problem especially for beginners and inexperienced surgeons. A wide-angle needle
      holder was designed to make the knot maneuver easier while also ensuring that the
      knot does not come out of the needle holder. In this study, it was planned to
      compare the wide-angle needle holder with the classic needle holder in regard to
      knot tying time. MATERIAL AND METHOD: A total of 11 male volunteers were randomly
      selected from freshmen students of the faculty of medicine, who had no experience
      of surgery or laparoscopic surgery. After the required training and practice,
      candidates were asked to tie 3 knots each in the training box using a classic
      needle holder and a wide-angle needle holder. Their knot tying times were
      recorded. RESULTS: Although the students had no experience, it was observed that
      they tied knots more easily and more comfortably using the wide-angle needle
      holder. It was found that the knot tying times with the wide-angle needle holder
      were quite short compared with the classic needle holder in all candidates. This
      difference was also statistically significant ( P = .01). CONCLUSION: We believe
      and claim that the use of a wide-angle needle holder during knot tying in
      laparoscopic surgery can facilitate knot tying and shorten the duration of the
      knotting, especially for inexperienced surgeons.

PMID- 29460693
TI  - Computer games for learning: an evidence based approach.

PMID- 29460692
TI  - Mediating Effects of Positive Thinking and Social Support on Suicide Resilience.
AB  - Suicide has been the second leading cause of death for 18- to 24-year-olds in the
      United States since 2011. The stress experienced by undergraduate college
      students has the potential to increase one's risk for suicide. Resilience theory
      was used as a theoretical framework to examine the interplay between risk and
      protective factors. A cross-sectional and correlational design was used to assess
      the mediating effects of positive thinking and/or social support on suicide
      resilience in 131 college students 18 to 24 years old who completed an online
      survey. The study found an indirect effect of self-esteem on suicide resilience
      through positive thinking and social support indicating that as self-esteem
      increases, positive thinking and social support also increase, which leads to an
      increase in resilience. The study also found a direct effect of self-esteem,
      positive thinking, and social support on suicide resilience. The findings inform
      the development of tailored interventions to build suicide resilience in college
      students.

PMID- 29460694
TI  - Control of exposure to hexavalent chromium concentration in shielded metal arc
      welding fumes by nano-coating of electrodes.
AB  - Background Cr(VI) is a suspected human carcinogen formed as a by-product of
      stainless steel welding. Nano-alumina and nano-titania coating of electrodes
      reduced the welding fume levels. Objective To investigate the effect of nano
      coating of welding electrodes on Cr(VI) formation rate (Cr(VI) FR) from a
      shielded metal arc welding process. Methods The core welding wires were coated
      with nano-alumina and nano-titania using the sol-gel dip coating technique. Bead
      on plate welds were deposited on SS 316 LN plates kept inside a fume test
      chamber. Cr(VI) analysis was done using an atomic absorption spectrometer (AAS).
      Results A reduction of 40% and 76%, respectively, in the Cr(VI) FR was observed
      from nano-alumina and nano-titania coated electrodes. Increase in the fume level
      decreased the Cr(VI) FR. Discussion Increase in fume levels blocked the UV
      radiation responsible for the formation of ozone thereby preventing the formation
      of Cr(VI).

PMID- 29460695
TI  - High seroprevalence and peripheral spatial distribution of visceral leishmaniasis
      among domestic dogs in an emerging urban focus in Central Brazil: a cross
      sectional study.
AB  - The Brazilian municipality of Rondonopolis is an emerging urban focus of intense
      transmission of visceral leishmaniasis (VL), where few investigations have
      addressed canine reservoirs. This study assessed the seroprevalence and spatial
      distribution of canine visceral leishmaniasis (CVL) in the urban area of
      Rondonopolis. A CVL serosurvey was conducted between October 2016 and February
      2017 using an immunochromatographic rapid test and enzyme-linked immunosorbent
      assay. Domestic dogs were sampled from 25 heterogeneous regions previously
      defined by the Spatial 'K'luster Analysis by Tree Edge Removal algorithm, which
      considered the socioeconomic and environmental features from the last demographic
      census. The CVL spatial distribution was analyzed by kernel density estimation
      (KDE) and spatial scan statistic. All the  autochthonous human VL cases reported
      between 2014 and 2016 were georeferenced. Of the 600 dogs tested, 115 were
      seropositive in both tests. The overall CVL prevalence was 19.2% (95%CI: 16.1
      22.3%), which varied widely among the evaluated regions (0.0-35.1%). Almost 25%
      of the sampled households (n = 405) had at least one infected dog. KDE
      demonstrated that positive CVL households were concentrated in the peripheral
      areas of the city. Spatial scan statistics detected a spatial cluster with
      significantly low CVL prevalence in the central region (relative risk = 0.37; p =
      0.04), where only one human VL case was reported. Thus, we demonstrated a high
      prevalence of CVL in domestic dogs from diverse socioeconomic and environmental
      urban contexts in Rondonopolis. The CVL cases were peripherally distributed and
      occurred more frequently in areas that had reported human VL.

PMID- 29460696
TI  - National health inequality monitoring: current challenges and opportunities.
AB  - National health inequality monitoring needs considerably more investment to
      realize equity-oriented health improvements in countries, including advancement
      towards the Sustainable Development Goals. Following an overview of national
      health inequality monitoring and the associated resource requirements, we
      highlight challenges that countries may encounter when setting up, expanding or
      strengthening national health inequality monitoring systems, and discuss
      opportunities and key initiatives that aim to address these challenges. We
      provide specific proposals on what is needed to ensure that national health
      inequality monitoring systems are harnessed to guide the reduction of health
      inequalities.

PMID- 29460697
TI  - Use of information communication technology and stress, burnout, and mental
      health in older, middle-aged, and younger workers - results from a systematic
      review.
AB  - The aim of this systematic review is to summarise quantitative studies in
      occupational settings observing the association between Information communication
      technology (ICT) and stress, and burnout, considering age as an effect modifier.
      A systematic review using PRISMA guidelines was conducted through the following
      bibliographic databases: PubMed, Web of Science, Psycinfo, and the Cochrane
      Library. Inclusion criteria were occupational settings and content relevant to
      our research question. Risk of bias was assessed using the Newcastle-Ottawa
      scale. Two interventional, 4 cohorts, and 29 cross-sectional studies were found.
      ICT use in occupational settings was associated with stress seen in cross
      sectional studies, but not in interventional studies. There was a concordant
      association with ICT and burnout in different study designs. Overall, there were
      no linear trends between age and technostress. We suggest that the observed
      associations were mostly present in the middle-aged working population and that
      these associations need to be supported in further studies.

PMID- 29460698
TI  - "Life Goes On." Everyday Tasks, Coping Self-Efficacy, and Independence: Exploring
      Older Adults' Recovery From Hip Fracture.
AB  - Older adults face many challenges in the first few months after hip fracture.
      Rehabilitation holds promise to assist the recovery process. Therefore, we used
      semistructured interviews to explore older adults' and allied health
      professionals' acceptance of a rehabilitation intervention for hip fracture, and
      we described perceptions of the early recovery period (<4 months). Interviews
      were recorded and transcribed verbatim; three authors independently read the
      transcripts multiple times and together developed themes guided by Interpretive
      Description. Older adults described the intervention as acceptable and provided
      valuable feedback for its future implementation. Older adults also provided
      reflections on their experience of fracture recovery. Themes that emerged
      included physical limitations and loss of independence, the long recovery time,
      and coping with additional complications of living with multimorbidity. To
      overcome challenges, older adults identified the need for social support and
      physical activity, balanced by their own personal outlook.

PMID- 29460699
TI  - Systemic Lupus Erythematosus (SLE) Responder Index response is associated with
      global benefit for patients with SLE.
AB  - A post-hoc analysis of pooled data from two Phase IIb trials (sifalimumab;
      NCT01283139, anifrolumab; NCT01438489) assessed the clinical significance of a
      Systemic Lupus Erythematosus (SLE) Responder Index (SRI(4)) response (Week 52)
      for 736 patients with moderate to severe SLE disease activity (study entry).
      SRI(4) responders achieved significantly greater improvements in clinical outcome
      measures (including percentages of patients with a >= 7-point reduction in SLE
      Disease Activity Index (SLEDAI)-2000 (2K), British Isles Lupus Assessment Group
      "A" or "2B" flare rate, and oral corticosteroid reduction to <=7.5 mg/day; change
      from baseline in Physician's Global Assessment; and numbers of SLEDAI-2K organ
      domains with improvement), as well as in patient-reported outcomes (Patient's
      Global Assessment, Functional Assessment of Chronic Illness Therapy-Fatigue;
      Short-Form 36 Health Survey Physical Component Summary, Mental Component Summary,
      Vitality domain scores) vs. nonresponders. Of patients with abnormal serologies,
      SRI(4) responders had numerically greater improvements (baseline to Week 52) in
      anti-double-stranded DNA concentrations vs. nonresponders ( p = 0.051), but there
      were no differences in C3/C4 concentration changes between the two groups. These
      results confirm previous findings in a different cohort, indicating that an
      SRI(4) response is associated with global clinical benefit.

PMID- 29460700
TI  - The lupus patient with positive rheumatoid factor.
AB  - Background Patients with systemic lupus erythematosus (SLE) may form clusters
      with clinical manifestations and autoantibodies. Objective The objective of this
      report is to study whether SLE patients with positive rheumatoid factor (RF) have
      a special clinical and/or serological profile. Methods A retrospective study of
      467 SLE patients seen at a single rheumatology unit was conducted.
      Epidemiological data (age, gender, age at disease onset, ethnic background and
      tobacco use), clinical data (malar rash, photosensitivity, oral ulcers, discoid
      lesions, serositis, glomerulonephritis, convulsions, psychosis, hemolytic anemia,
      leukopenia, lymphocytopenia, arthritis and hypothyroidism) and serological
      profile (anti-dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-RNP, anti-Sm, IgG aCL, IgM
      aCL, lupus anticoagulant, direct Coombs and RF) were collected. Patients with
      positive and negative RF were compared. Results RF was found in 24.9% of the
      sample. In univariate analysis, RF was positively associated with butterfly rash
      ( p = 0.04), anti-Ro ( p = 0.03), anti-Sm antibodies ( p = 0.01) and
      hypothyroidism ( p = 0.01) and negatively associated with glomerulonephritis ( p
      = 0.003). Logistic regression showed that only glomerulonephritis ( p = 0.03; OR
      = 0.45; 95% CI = 0.21-0.93) and anti-Ro ( p = 0.009; OR = 2.3; 95% CI = 1.24
      4.57) were independent associations. Conclusion In our sample RF was associated
      with protection from glomerulonephritis and with higher prevalence of anti-Ro
      antibodies.

PMID- 29460701
TI  - Anti-dsDNA titre in female systemic lupus erythematosus patients: relation to
      disease manifestations, damage and antiphospholipid antibodies.
AB  - Background Attempts are ongoing to unveil unresolved queries about anti-double
      stranded deoxyribonucleic acid (anti-dsDNA), their precise pathogenic effects and
      to what extent blocking them would be a useful therapeutic goal. Objectives The
      aim of the present study was to determine the anti-dsDNA antibodies titre in
      systemic lupus erythematosus (SLE) patients and investigate their relation to the
      disease characteristics, activity, damage and antiphospholipid autoantibodies
      (aPL). Methods Seventy female SLE patients and 35 age- and sex-matched controls
      were included. The anti-dsDNA level and aPL were measured. Systemic Lupus
      Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International
      Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR
      DI) were assessed. Results The mean age of the patients was 27.5 +/- 5.1 years,
      disease duration 7.7 +/- 5.4 years, and SLEDAI and SLICC/ACR-DI scores were 6.8
      +/- 8.04 and 1.2 +/- 1.3, respectively. Anti-dsDNA was positive in 61.4% of the
      patients and the titre (133.2 +/- 100.5 IU/ml) was significantly higher compared
      to controls (22.03 +/- 17.2 IU/ml) ( p < 0.0001). The anti-dsDNA level was
      significantly increased in those with musculoskeletal manifestations ( p = 0.007)
      and positive anti-beta2 glycoprotein (anti-beta2GP) ( p = 0.037) and decreased in
      those with neuropsychiatric manifestations ( p = 0.004) and those receiving
      cyclophosphamide (CYC) ( p = 0.013). The anti-dsDNA level tended to be higher in
      active patients. The anti-dsDNA titre significantly correlated with the
      erythrocyte sedimentation rate ( p = 0.001), anticardiolipin IgG and IgA
      antibodies ( p = 0.008) and anti-beta2GP IgG ( p = 0.03) and IgA ( p = 0.002) and
      inversely with the total leucocytic count ( p < 0.0001) and SLICC/ACR-DI ( p =
      0.001). Conclusion Anti-dsDNA is remarkably increased in SLE patients especially
      those with musculoskeletal manifestations and aPL. A protective role seems likely
      in those with neuropsychiatric manifestations and those receiving CYC and may
      form a shield against disease tissue damage.

PMID- 29460702
TI  - Comparison between disease onset patterns of Egyptian juvenile and adult systemic
      lupus erythematosus (single centre experience).
AB  - Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease
      that occurs worldwide in both children and adults, with different disease
      manifestations, activity and severity between them. Objectives To analyse the
      difference in disease onset patterns and activity in Egyptian children and adults
      with SLE. Methods A retrospective cohort study conducted on 298 Egyptian SLE
      patients, 215 adults (a-SLE) (>18 years) and 83 children (j-SLE) (<=18 years).
      Disease onset, clinical manifestations and laboratory investigations were
      recorded. The systemic lupus erythematosus disease activity index (SLEDAI) was
      used to assess disease onset activity; renal biopsy was performed for all cases
      affected with renal symptoms. Results A total of 215 a-SLE (F/M: 14.4/1), mean
      age 29.65 +/- 10.235 years, and 83 j-SLE (F/M: 5.4/1), mean age at diagnosis
      12.63 +/- 3.112 years. The most frequent initial a-SLE symptoms were
      constitutional (88.8%), mucocutaneous (71.2%), haematological (64.2%), articular
      (62.3%), renal (43.7%), vascular (15.3%), serositis (14.4%) and finally central
      nervous system (11.6%). There were no significant differences between a-SLE and j
      SLE with regard to constitutional, mucocutaneous, renal, vascular and serositis
      manifestations, which were 92.8%, 74.7%, 53%, 16.9% and 10.8%, respectively, but
      the j-SLE haematological (88%) and central nervous system (30.1%) manifestations
      were significantly higher than a-SLE and articular manifestations were
      significantly lower in j-SLE (14.5%) than a-SLE. Antinuclear antibodies were
      positive for 95.3% of a-SLE and 97.6% of j-SLE. Anti-dsDNA was positive for 84.7%
      a-SLE and was significantly higher in j-SLE (92.8%). The SLEDAI score was 12.23
      +/- 4.966 in a-SLE and was significantly higher in j-SLE (27.13 +/- 19.968).
      International Society of Nephrology lupus nephritis classes III and IV (42.4%)
      were the commonest findings in a-SLE; however, classes I and III (57.9%) were the
      commonest in j-SLE. Conclusions SLE had a wide variety of clinical and
      immunological manifestations, with some similarity and differences between a-SLE
      and j-SLE; juvenile onset lupus had a higher SLEDAI with more aggressive initial
      manifestations than a-SLE.

PMID- 29460703
TI  - Practice insights on patient care-management overview for chemoradiation toxic
      mucositis-guidelines, guideline-supported therapies and high potency polymerized
      cross-linked sucralfate (ProThelial).
AB  - Aim To offer a practice insight for the management of chemoradiation toxic
      mucositis. Method Review chemoradiation toxic mucositis, its pathobiology and
      breadth of symptom presentation. Review mucositis guidelines and guideline
      supported anti-mucositis therapies. Offer guidance on guidelines and an
      abbreviated review of high potency cross-linked sucralfate for management of
      chemoradiation toxic mucositis. Result There are six major mucositis guidelines
      but only one that is current and regularly updated. Guidelines from the
      Multinational Association Supportive Cancer Care suggest 14 interventions gleaned
      from controlled trials, 12 of which are off-label uses of therapies that offer
      statistically significant but incrementally beneficial outcomes. Several evidence
      based limitations of guidelines are discussed. Data on high potency polymerized
      cross-linked sucralfate confirming complete prevention and rapid (2-3 days)
      elimination, sustained throughout cancer treatment is verified as high quality
      evidence in accordance to standards adopted by Agency for Healthcare Research and
      Quality. A 96-97% reduction in mucositis duration qualifies as a positive
      Glasziou treatment effect, which is discussed as an additional measure of
      evidence-based medicine. Conclusion Statistically significant but fractional
      treatment effects of guideline-supported interventions are not likely to
      substantially alter the course of mucositis when it occurs nor completely prevent
      its onset. Complete prevention and rapid sustained elimination should be the
      goal, therefore high potency polymerized cross-linked sucralfate may be useful.
      Where guidelines fail, institution-based protocols led by oncology pharmacists
      could succeed. In an effort to eliminate toxic mucositis, enhance compliance to
      chemoradiation regimens, and improve survival, such protocols for practice may
      verify pharmacoeconomic benefits, if any, in using high potency polymerized cross
      linked sucralfate to manage toxic mucositis.

PMID- 29460704
TI  - Current status of drug vial optimization use to prevent waste associated with
      injectable anticancer agents.

PMID- 29460705
TI  - A single center retrospective cohort study comparing low-molecular-weight
      heparins to direct oral anticoagulants for the treatment of venous
      thromboembolism in patients with cancer - A real world experience.
AB  - Introduction Low-molecular-weight heparins are the standard treatment for cancer
      associated thrombosis. Recently, direct oral anticoagulants are a new option for
      thrombosis treatment; however, data supporting the use of direct oral
      anticoagulants for cancer-associated thrombosis are limited. Objectives The
      primary objective of this study was to determine the rate of recurrent cancer
      associated thrombosis and major bleeding within 6 months of starting either low
      molecular-weight heparin or direct oral anticoagulant for treatment of cancer
      associated thrombosis. Secondary objectives were to determine the rates of
      clinically relevant-non-major bleeding and all-cause mortality. Patients/methods
      This is a retrospective cohort study including adults with cancer-associated
      thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant
      between 2010 and 2016 at the Ohio State University. Medical records were reviewed
      for 6 months after initiation of anticoagulation or until the occurrence of
      recurrent cancer-associated thrombosis, major bleeding, cessation of
      anticoagulation of interest, or death, whichever occurred first. Results Four
      hundred and eighty patients were included (290 low-molecular-weight heparin and
      190 direct oral anticoagulant). Patients treated with direct oral anticoagulant
      were found to carry "lower risk" features including cancer with lower VTE risk
      and lower rate of metastatic disease. After adjustment for baseline differences,
      there was no significant difference in the rate of recurrent cancer-associated
      thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant,
      p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct
      oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a
      select population of cancer patients with VTE, direct oral anticoagulant use can
      be as effective and safe compared to the standard therapy with low-molecular
      weight heparin.

PMID- 29460706
TI  - Using a treatment diary to improve the medication adherence in patients with
      chronic myeloid leukaemia.
AB  - Purpose The aim of this study was to verify whether the distribution of a
      treatment diary by a pharmacist could influence the adherence to oral treatment
      with imatinib, nilotinib, and dasatinib in patients with chronic myeloid
      leukaemia. Methods The level of adherence was calculated using the received daily
      dose/prescribed daily dose ratio and compared between patients who used a diary
      and those who did not. Results Forty-four (35.8%) of 123 patients with chronic
      myeloid leukaemia completed the diary: 20 (45.4%) receiving imatinib, 17 (38.6%)
      receiving nilotinib, and seven (15.9%) receiving dasatinib. Treatment adherence
      with the diary calculated using received daily dose/prescribed daily dose method
      was 93.6% (imatinib 94.9%, nilotinib 91.1%, and dasatinib 95.8%). Adherence
      during the period without a diary was 86.5% (84.9, 87.4, and 90%). Adherence was
      significantly greater with than without a diary (p < 0.0001). Conclusions The
      findings of this study that, in the case of chronic diseases, direct pharmacist
      patient contact is important in order to maintain high levels of adherence, and a
      treatment diary is a valid means of doing this. According to these data, it is
      necessary to support similar patient-oriented programmes in order to ensure high
      levels of adherence and optimize drug management.

PMID- 29460707
TI  - Using Microscale Thermophoresis to Characterize Hits from High-Throughput
      Screening: A European Lead Factory Perspective.
AB  - High-throughput screening (HTS) is a proven method for discovering new lead
      matter for drug discovery and chemical biology. To maximize the likelihood of
      identifying genuine binders to a molecular target, and avoid wasting resources
      following up compounds with unproductive/nonspecific mechanisms of action, it is
      important to employ a range of assays during an HTS campaign that build
      confidence of target engagement for hit compounds. Biophysical methods that
      measure direct target/compound engagement have established themselves as key
      techniques in generating this confidence, and they are now integral to the latter
      stages of HTS triage at the European Lead Factory (ELF). One relatively new
      technique that the ELF is using is microscale thermophoresis (MST), which
      measures the differences in rate of movement through a temperature gradient that
      are caused when single molecular species form complexes. Here we provide an
      overview of the MST assay development workflow that the ELF employs and a
      perspective of our experience to date of using MST to triage the output of HTS
      campaigns and how it compares and contrasts with the use of other biophysical
      techniques.

PMID- 29460708
TI  - PCSK9 inhibition in PAD patients - a rising star in secondary prevention?

PMID- 29460709
TI  - Ionic liquid as a potential solvent for preparation of collagen-alginate
      hydroxyapatite beads as bone filler.
AB  - In this study, collagen/alginate/hydroxyapatite beads having different
      proportions were prepared as bone fillers for the restoration of osteological
      defects. Ionic liquid was used to dissolve the collagen and subsequently the
      solution was mixed with sodium alginate solution. Hydroxyapatite was added in
      different proportions, with the rationale to enhance mechanical as well as
      biological properties. The prepared solutions were given characteristic bead
      shapes by dropwise addition into calcium chloride solution. The prepared beads
      were characterized using FTIR, XRD, TGA and SEM analysis. Microhardness testing
      was used to evaluate the mechanical properties. The prepared beads were
      investigated for water adsorption behavior to ascertain its ability for body
      fluid uptake and adjusted accordingly to the bone cavity. Drug loading and
      subsequently the antibacterial activity was investigated for the prepared beads.
      The biocompatibility was assessed using the hemolysis testing and cell
      proliferation assay. The prepared collagen-alginate-HA beads, having
      biocompatibility and good mechanical properties, have showed an option of
      promising biologically active bone fillers for bone regeneration.

PMID- 29460710
TI  - Doctors as Stewards of medicare, or not: CAMSI, MRG, CDM, DRHC and the thin
      alphabet soup of physician support.
AB  - Physicians are deeply involved in Canadian medicare because it is through
      medicare that they are paid. However, from its origins to the present physicians 
      as a profession - have not been strong supporters of medicare. Fearing loss of
      income and individual autonomy, they have frequently opposed it with criticisms,
      strikes, threatened job action and lawsuits. Some opponents are unaware that
      medicare was a boon to physician income, and many fail to connect medicare with
      responsibility for improving the health status of the country. This paper will
      trace physician involvement, support and opposition to medicare from its
      inception to the present, with special attention to small physician organizations
      that have supported medicare. It will close with a proposal for how doctors could
      display greater stewardship.

PMID- 29460711
TI  - Subclinical inflammation affects iron and vitamin A but not zinc status
      assessment in Senegalese children and Cambodian children and women - ERRATUM.

PMID- 29460712
TI  - Rhythmic low-field magnetic stimulation may improve depression by increasing
      brain-derived neurotrophic factor.
AB  - BACKGROUND: Low-field magnetic stimulation (LFMS) has mood-elevating effect, and
      the increase of brain-derived neurotrophic factor (BDNF) is associated with
      antidepressant treatment. We evaluated the effects and association with BDNF of
      rhythmic LFMS in the treatment of major depressive disorder (MDD). METHODS: A
      total of 22 MDD patients were randomized to rhythmic alpha stimulation (RAS) or
      rhythmic delta stimulation (RDS), with 5 sessions per week, lasting for 6 weeks.
      Outcomes assessments included the 17-item Hamilton Depression Rating Scale (HAMD
      17), the Hamilton Anxiety Rating Scale (HAMA), and the Clinical Global
      Impressions-Severity scale (CGI-S) at baseline and at weeks 1, 2, 3, 4, and 6.
      Serum BDNF level was measured at baseline and at weeks 2, 4, and 6. RESULTS: HAMD
      17, HAMA, and CGI-S scores were significantly reduced with both RAS and RDS. RAS
      patients had numerically greater reductions in HAMD-17 scores than RDS patients
      (8.9 +/- 7.4 vs. 6.2 +/- 6.2, effect size [ES]=0.40), while RDS patients had
      greater improvement in HAMA scores (8.2 +/- 8.0 vs. 5.3 +/- 5.8, ES=0.42). RAS
      was associated with clinically relevant advantages in response (54.5% vs. 18.2%,
      number-needed-to-treat [NNT]=3) and remission (36.4% vs. 9.1%, NNT=4). BDNF
      increased significantly during the 6-week study period (p<0.05), with greater
      increases in RAS at weeks 4 and 6 (ES=0.66-0.76) and statistical superiority at
      week 2 (p=0.034, ES=1.23). Baseline BDNF in the 8 responders (24.8+/-9.0 ng/ml)
      was lower than in the 14 nonresponders (31.1+/-7.3 ng/ml, p=0.083, ES=-0.79), and
      BDNF increased more in responders (8.9+/-7.8 ng/ml) than in nonresponders (1.8+/
      3.5 ng/ml, p=0.044). The change in BDNF at week 2 was the most strongly predicted
      response (p=0.016). CONCLUSIONS: Rhythmic LFMS was effective for MDD. BDNF may
      moderate/mediate the efficacy of LFMS.

PMID- 29460713
TI  - Assessing the Ability of Hospital Diagnosis Codes to Detect Inpatient Exposure to
      Antibacterial Agents.
AB  - OBJECTIVE Because antibacterial history is difficult to obtain, especially when
      the exposure occurred at an outside hospital, we assessed whether infection
      related diagnostic billing codes, which are more readily available through
      hospital discharge databases, could infer prior antibacterial receipt. DESIGN
      Retrospective cohort study. PARTICIPANTS This study included 121,916
      hospitalizations representing 78,094 patients across the 3 hospitals. METHODS We
      obtained hospital inpatient data from 3 Chicago-area hospitals. Encounters were
      categorized as "infection" if at least 1 International Classification of Disease,
      Ninth Revision, Clinical Modification (ICD-9-CM) code indicated a bacterial
      infection. From medication administration records, we categorized antibacterial
      agents and calculated total therapy days using Centers for Disease Control and
      Prevention (CDC) definitions. We evaluated bivariate associations between
      infection encounters and 3 categories of antibacterial exposure: any, broad
      spectrum, or surgical prophylaxis. We constructed multivariable models to
      evaluate adjusted risk ratios for antibacterial receipt. RESULTS Of the 121,916
      inpatient encounters (78,094 patients) across the 3 hospitals, 24% had an
      associated infection code, 47% received an antibacterial, and 13% received a
      broad-spectrum antibacterial. Infection-related ICD-9-CM codes were associated
      with a 2-fold increase in antibacterial administration compared to those lacking
      such codes (RR, 2.29; 95% confidence interval [CI], 2.27-2.31) and a 5-fold
      increased risk for broad-spectrum antibacterial administration (RR, 5.52; 95% CI,
      5.37-5.67). Encounters with infection codes had 3 times the number of
      antibacterial days. CONCLUSIONS Infection diagnostic billing codes are strong
      surrogate markers for prior antibacterial exposure, especially to broad-spectrum
      antibacterial agents; such an association can be used to enhance early
      identification of patients at risk of multidrug-resistant organism (MDRO)
      carriage at the time of admission. Infect Control Hosp Epidemiol 2018;39:377-382.

PMID- 29460715
TI  - Comparative Medicine Unveils New Cover Concept.

PMID- 29460714
TI  - Seroprevalence of Dengue Antibodies in Three Urban Settings in Yucatan, Mexico.
AB  - Dengue transmission in Mexico has become a major public health problem. Few
      epidemiological studies have examined the seroprevalence of dengue in Mexico, and
      recent estimates are needed to better understand dengue transmission dynamics. We
      conducted a dengue seroprevalence survey among 1,668 individuals including all
      age groups in three urban settings in Yucatan, Mexico. Children (< 19 years old)
      were selected randomly from schools. The adults (>= 19 years old) were selected
      from healthcare facilities. Participants were asked to provide a venous blood
      sample and to answer a brief questionnaire with demographic information. Previous
      exposure to dengue was determined using indirect immunoglobulin G enzyme-linked
      immunosorbent assay. The overall seroprevalence was 73.6%. The age-specific
      seroprevalence increased with age, going from 51.4% (95% confidence interval [CI]
      = 45.0-57.9%) in children <= 8 years to 72% (95% CI = 66.3-77.2%) in the 9- to 14
      years old. The highest seroprevalence was 83.4% (95% CI = 77-82.2%) in adults
      greater than 50 years. The seroprevalence in Merida was 68.6% (95% CI = 65-72%),
      in Progreso 68.7% (95% CI = 64.2-72.8%), and in Ticul 85.3% (95% CI = 81.9
      88.3%). Ticul had the highest seroprevalence in all age groups. Logistic
      regression analysis showed that age and city of residence were associated with
      greater risk of prior dengue exposure. The results highlight the level of past
      exposure to dengue virus including young children. Similar studies should be
      conducted elsewhere in Mexico and other endemic countries to better understand
      the transmission dynamics of dengue.

PMID- 29460716
TI  - Role of Wild-type and Recombinant Human T-cell Leukemia Viruses in
      Lymphoproliferative Disease in Humanized NSG Mice.
AB  - Chronic infection with human T-cell leukemia virus type 1 (HTLV1) can lead to
      adult T-cell leukemia (ATL). In contrast, infection with HTLV2 does not lead to
      leukemia, potentially because of distinct virus-host interactions and an active
      immune response that controls virus replication and, therefore, leukemia
      development. We created a humanized mouse model by injecting human umbilical-cord
      stem cells into the livers of immunodeficient neonatal NSG mice, resulting in the
      development of human lymphocytes that cannot mount an adaptive immune response.
      We used these mice to compare the ability of molecular clones of HTLV1, HTLV2,
      and select recombinant viruses to induce leukemia-lymphoma in vivo. Infection
      with HTLV1 strongly stimulated the proliferation of CD4+ T cells, whereas HTLV2
      preferentially stimulated the proliferation of CD8+ T cells; both HTLV1 and HTLV2
      induced lymphoproliferative disease. Uninfected and HTLV-infected humanized mice
      both showed granulomatous inflammation as a background lesion. Similarly,
      recombinant viruses that expressed the HTLV1 envelope protein (Env) on an HTLV2
      background (HTLV2-Env1) or Env2 on an HTLV1 background (HTLV1-Env2) induced
      lymphoproliferative disease. HTLV2-Env1 stimulated the proliferation of CD4+ T
      cells, whereas HTLV1-Env2 stimulated both CD4+ and CD8+ T-cell subsets. Our
      results show that T-cell transformation in vivo is guided by the Env protein of
      the virus. Furthermore, our humanized mouse model is useful for exploring the
      preferred T-cell tropisms of HTLV1 and HTLV2.

PMID- 29460717
TI  - Strain-specific Differences in the Effects of Lymphocytes on the Development of
      Insulin Resistance and Obesity in Mice.
AB  - Obesity is characterized as a chronic, low-grade inflammatory disease owing to
      the infiltration of the adipose tissue by macrophages. Although the role of
      macrophages in this process is well established, the role of lymphocytes in the
      development of obesity and metabolism remains less well defined. In the current
      study, we fed WT and Rag1-/- male mice, of C57BL/6J and BALB/c backgrounds, high
      fat diet (HFD) or normal diet for 15 wk. Compared with WT mice, Rag1-/- mice of
      either of the examined strains were found less prone to insulin resistance after
      HFD, had higher metabolic rates, and used lipids more efficiently, as shown by
      the increased expression of genes related to fatty acid oxidation in epidydimal
      white adipose tissue. Furthermore, Rag1-/- mice had increased Ucp1 protein
      expression and associated phenotypic characteristics indicative of beige adipose
      tissue in subcutaneous white adipose tissue and increased Ucp1 expression in
      brown adipose tissue. As with inflammatory and other physiologic responses
      previously reported, the responses of mice to HFD show strain-specific
      differences, with increased susceptibility of C57BL/6J as compared with BALB/c
      strain. Our findings unmask a crucial role for lymphocytes in the development of
      obesity and insulin resistance, in that lymphocytes inhibit efficient dissipation
      of energy by adipose tissue. These strain-associated differences highlight
      important metabolic factors that should be accommodated in disease modeling and
      drug testing.

PMID- 29460718
TI  - Cutaneous Dermatophilosis in a Meadow Jumping Mouse (Zapus hudsonius).
AB  - A laboratory-housed, wild-caught, subadult, male meadow jumping mouse (Zapus
      hudsonius) presented with extensive scaling of the face, limbs, and tail and
      severe edema of the paws. Postmortem examination revealed marked distal limb
      edema with focal digital hematomas and white scales, scabs, and crusts affecting
      the majority of nonhaired skin. Histopathologic analysis revealed severe,
      multifocal, chronic-active exudative and proliferative dermatitis characterized
      by multilaminated crusts covering the epidermis. The epidermis was expanded by
      hyperkeratosis, acanthosis, and hyperplasia. The superficial dermis contained
      moderate edema, hemorrhage, and pigmentary incontinence, and was infiltrated by
      granulocytes and mononuclear cells. The laminated crusts contained numerous
      branching filaments of gram-positive coccoid bodies arranged in parallel rows,
      consistent with cutaneous Dermatophilus congolensis infection. This diagnosis was
      confirmed through bacterial culture and 16S rRNA PCR analysis. In the presented
      case, factors that might have contributed to disease progression include climatic
      conditions at the capture site and stress associated with trapping and laboratory
      housing.

PMID- 29460719
TI  - Characterization of Cotton Rat (Sigmodon hispidus) Eosinophils, Including Their
      Response to Respiratory Syncytial Virus Infection.
AB  - Eosinophils have been postulated to play a protective role against infection with
      respiratory syncytial virus (RSV), increase the severity of allergic asthma
      during respiratory viral infection, and drive vaccine-enhanced disease. To
      address these questions in the cotton rat model of RSV infection, we
      characterized cotton rat eosinophils by electron microscopy as well as by
      bronchoalveolar lavage and histology of lung sections. Using these methods, we
      demonstrated that eosinophils comprise approximately half of all cells in the
      bronchoalveolar lavage fluids from cotton rats. The function of these cells was
      comparable to that of eosinophils of other species. Ex vivo, eosinophils
      stimulated with calcium ionophores secreted eosinophil peroxidase. In vivo,
      treatment with house dust mite antigen increased eosinophil numbers in lung.
      Infection with Staphylococcus aureus lead to a marked increase in neutrophils
      without an increase in eosinophils, and eosinophil numbers were not influenced by
      infection with influenza virus or measles virus. Similarly, infection with RSV
      did not result in an increase in eosinophils. Lastly, RSV infection did not
      increase eosinophil recruitment into the lung after challenge with house dust
      mite antigen, but it did increase eosinophil recruitment into the lungs of cotton
      rats previously immunized with formalin-inactivated RSV vaccine, thus
      contributing to vaccine-enhanced disease.

PMID- 29460720
TI  - Humane Endpoints for Guinea Pigs Used for Mycobacterium tuberculosis Vaccine
      Research.
AB  - Guinea pigs are a commonly used model for tuberculosis vaccine research. Loss of
      body weight is the most frequently described humane endpoint for animals used in
      these studies. During a chronic study, we noted labored breathing in some
      tuberculosis-infected guinea pigs. To develop consistent humane endpoints for
      these guinea pigs, we performed an observational study using multiple clinical
      signs. A combination of body weight loss, labored breathing, and activity level
      during handling estimated the time to euthanasia within approximately 7 d.
      Histologic severity scores of lesions in the cranial or caudal lung lobe (or
      both) supported clinical endpoints. This study presents humane endpoints for the
      refinement of studies using guinea pigs in tuberculosis research.

PMID- 29460721
TI  - Duodenal Cannulation in Pigs (Sus scrofa) as a Drug Delivery Method.
AB  - Currently available animal models for delivery of drug capsules and
      pharmacokinetic testing are limited by either intersubject variability in gastric
      emptying time or the need to sedate animals when using targeted delivery methods
      of drug capsules. With the increasing development of large-molecule biologics,
      better in vivo models for testing the pharmacokinetics of capsule-delivered drugs
      are urgently needed. To this end, we made engineering modifications to an
      existing bovine surgical cannula device, successfully implanted this modified
      cannula into pigs, and delivered drug capsules directly to the proximal duodenum.
      In our porcine model, capsule insertion and serial blood samples were all
      acquired without the use of sedatives. Furthermore, we were able to maintain
      cannulated pigs for weekly pharmacokinetic testing for more than 18 mo, with
      minimal postoperative complications. This study demonstrates a novel and
      effective porcine model of sedation-free drug delivery and blood collection that
      eliminates inconsistencies associated with models that require either gastric
      emptying or animal sedation.

PMID- 29460722
TI  - Cutaneous Toxicity in a Laboratory Beagle (Canis lupus familiaris) after Chronic
      Administration of Doxorubicin Hydrochloride.
AB  - An adult female beagle (Canis lupus familiaris) used in a model of doxorubicin
      induced cardiomyopathy presented with epithelial desquamation on the shoulders
      and ventrum after receiving the 8th weekly intravenous dose of the free form of
      doxorubicin (20 mg/m2; total accumulation, 160 mg/m2). The lesions were
      empirically treated with topical disinfectants and topical and systemic
      antibiotics. Despite treatment, the lesions progressed and ulcerated. Bacterial
      culture revealed Staphylococcus aureus, but trichogram, skin scraping, and fungal
      culture were negative for microorganisms. Skin biopsies revealed epidermal and
      apocrine gland hyperplasia, apocrine gland dilation, abnormal maturation of
      epithelial keratinocytes, and perivascular lymphocytic infiltration. These
      histopathologic findings resemble those in humans and canines after chronic
      administration of doxorubicin-containing pegylated liposomes. Here we report a
      clinical presentation after chronic administration of the free form of
      doxorubicin. In dogs, cutaneous toxicity after administration of pegylated
      liposomal doxorubicin is most often localized to the footpads, limbs, and
      axillary and urogenital regions. In the current case, lesions affected the
      ventrum and trunk but did not involve the footpads or axillary or urogenital
      regions.

PMID- 29460723
TI  - Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in
      Cynomolgus Macaques (Macaca fasicularis).
AB  - Here we present the results of experiments involving cynomolgus macaques, in
      which a model of traumatic spinal cord injury (TSCI) was created by using a
      balloon catheter inserted into the epidural space. Prior to the creation of the
      lesion, we inserted an EMG recording device to facilitate measurement of tail
      movement and muscle activity before and after TSCI. This model is unique in that
      the impairment is limited to the tail: the subjects do not experience limb
      weakness, bladder impairment, or bowel dysfunction. In addition, 4 of the 6
      subjects received a combination treatment comprising thyrotropin releasing
      hormone, selenium, and vitamin E after induction of experimental TSCI. The
      subjects tolerated the implantation of the recording device and did not
      experience adverse effects due the medications administered. The EMG data were
      transformed into a metric of volitional tail moment, which appeared to be valid
      measure of initial impairment and subsequent natural or treatment-related
      recovery. The histopathologic assessment demonstrated widespread axon loss at the
      site of injury and areas cephalad and caudad. Histopathology revealed evidence of
      continuing inflammation, with macrophage activation. The EMG data did not
      demonstrate evidence of a statistically significant treatment effect.

PMID- 29460724
TI  - Pseudoaneurysm and Arteriovenous Fistula in a Rhesus Macaque (Macaca mulatta).
AB  - An 8-y-old female rhesus macaque (Macaca mulatta) presented for swelling of the
      left lower limb distal to the inguinal region and associated with the femoral
      artery. Physical and ultrasound examinations suggested an arteriovenous fistula
      combined with a pseudoaneurysm. After review of possible treatment options, we
      determined that open surgical repair was the best course of action. The
      pseudoaneurysm and arteriovenous fistula were surgically resected, and the
      macaque recovered without complication.

PMID- 29460726
TI  - Animal Models & Translational Medicine: Quality and Reproducibility of
      Experimental Design | AISAL Symposium.

PMID- 29460725
TI  - Surgical Treatment of Recurrent Rectal Prolapse in an Adult Female Black-crested
      Mangabey (Lophocebus aterrimus) by Colopexy.
AB  - A 13-y-old, multiparous female black-crested mangabey (Lophocebus aterrimus)
      underwent surgical treatment for chronically recurring rectal prolapse by
      laparotomy and subsequent colopexy. Initially, a laparoscopic approach was
      attempted but was converted to an open approach after intraabdominal adhesions
      were noted. The colopexy was performed through a ventral midline incision, with
      no complications intraoperatively or postoperatively. The predisposing factors
      responsible for the development of this condition likely were related to pelvic
      floor weakness due to multiple past pregnancies. Transport-associated stressors
      likely contributed to the acute worsening of this patient's condition. Rectal
      prolapse is a common condition in laboratory-housed NHP. This case report
      describes an effective surgical treatment for recurring or otherwise nonreducible
      rectal prolapse in these species.

PMID- 29460727
TI  - A Comparative Analysis of Economic Cost of Podoconiosis and Leprosy on Affected
      Households in the Northwest Region of Cameroon.
AB  - Leprosy and podoconiosis (podo) are neglected tropical diseases that cause severe
      disfigurement and disability, and may lead to catastrophic health expenditure and
      hinder economic development of affected persons and households. This study
      compared economic costs of both diseases on affected households with unaffected
      neighboring households in the Northwest Region (N.W.R.) of Cameroon. A matched
      comparative cross-sectional design was used enrolling 170 households (43 podo
      case households, 41 podo control households, 43 leprosy case households, and 43
      leprosy control households) from three health districts in the N.W.R. Direct
      treatment costs for podo averaged 142 United State dollar (USD), compared with
      zero for leprosy (P < 0.001). This was also reflected in the proportion of annual
      household income consumed (0.4 versus 0.0, respectively, P < 0.001). Both
      diseases caused considerable reductions in working days (leprosy 115 versus podo
      135 days. P for comparison < 0.001). The average household income was
      considerably lower in podo-affected households than unaffected households (410
      versus 913 USD, P = 0.01), whereas income of leprosy-affected households was
      comparable to unaffected households (329 versus 399 USD, P = 0.23). Both leprosy
      and podo cause financial burdens on affected households, but those on podo
      affected families are much greater. These burdens occur through direct treatment
      costs and reduced ability to work. Improved access to public health interventions
      for podo including prevention, morbidity management and disability prevention are
      likely to result in economic returns to affected families. In Cameroon, one
      approach to this would be through subsidized health insurance for these
      economically vulnerable households.

PMID- 29460729
TI  - Use of Genome Sequencing to Define Institutional Influenza Outbreaks, Toronto,
      Ontario, Canada, 2014-15.
AB  - Adequacy of the current clinical definition of institutional influenza outbreaks
      is unclear. We performed a retrospective genome sequencing and epidemiologic
      analysis of institutional influenza outbreaks that occurred during the 2014-15
      influenza season in Toronto, Canada. We sequenced the 2 earliest submitted
      samples positive for influenza A(H3N2) from each of 38 reported institutional
      outbreaks in long-term care facilities. Genome sequencing showed most outbreak
      pairs identified by using the current clinical definition were highly related.
      Inclusion of surveillance samples demonstrated that outbreak sources were likely
      introductions from broader circulating lineages. Pairwise distance analysis using
      majority genome and hemagglutinin-specific genes enabled identification of
      thresholds for discrimination of within and between outbreak pairs; the area
      under the curve ranged 0.93-0.95. Routine genome sequencing for defining
      influenza outbreaks in long-term care facilities is unlikely to add significantly
      to the current clinical definition. Sequencing may prove most useful for
      investigating sources of outbreak introductions.

PMID- 29460728
TI  - Capsule Typing of Haemophilus influenzae by Matrix-Assisted Laser
      Desorption/Ionization Time-of-Flight Mass Spectrometry.
AB  - Encapsulated Haemophilus influenzae strains belong to type-specific genetic
      lineages. Reliable capsule typing requires PCR, but a more efficient method would
      be useful. We evaluated capsule typing by using matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Isolates of
      all capsule types (a-f and nontypeable; n = 258) and isogenic capsule
      transformants (types a-d) were investigated. Principal component and biomarker
      analyses of mass spectra showed clustering, and mass peaks correlated with
      capsule type-specific genetic lineages. We used 31 selected isolates to construct
      a capsule typing database. Validation with the remaining isolates (n = 227)
      showed 100% sensitivity and 92.2% specificity for encapsulated strains (a-f; n =
      61). Blinded validation of a supplemented database (n = 50) using clinical
      isolates (n = 126) showed 100% sensitivity and 100% specificity for encapsulated
      strains (b, e, and f; n = 28). MALDI-TOF mass spectrometry is an accurate method
      for capsule typing of H. influenzae.

PMID- 29460730
TI  - Major Threat to Malaria Control Programs by Plasmodium falciparum Lacking
      Histidine-Rich Protein 2, Eritrea.
AB  - False-negative results for Plasmodium falciparum histidine-rich protein (HRP) 2
      based rapid diagnostic tests (RDTs) are increasing in Eritrea. We investigated
      HRP gene 2/3 (pfhrp2/pfhrp3) status in 50 infected patients at 2 hospitals. We
      showed that 80.8% (21/26) of patients at Ghindae Hospital and 41.7% (10/24) at
      Massawa Hospital were infected with pfhrp2-negative parasites and 92.3% (24/26)
      of patients at Ghindae Hospital and 70.8% (17/24) at Massawa Hospital were
      infected with pfhrp3-negative parasites. Parasite densities between pfhrp2
      positive and pfhrp2-negative patients were comparable. All pfhrp2-negative
      samples had no detectable HRP2/3 antigen and showed negative results for HRP2
      based RDTs. pfhrp2-negative parasites were genetically less diverse and formed 2
      clusters with no close relationships to parasites from Peru. These parasites
      probably emerged independently by selection in Eritrea. High prevalence of pfhrp2
      negative parasites caused a high rate of false-negative results for RDTs.
      Determining prevalence of pfhrp2-negative parasites is urgently needed in
      neighboring countries to assist case management policies.

PMID- 29460731
TI  - Multistate Epidemiology of Histoplasmosis, United States, 2011-2014
AB  - Histoplasmosis is one of the most common mycoses endemic to the United States,
      but it was reportable in only 10 states during 2016, when a national case
      definition was approved. To better characterize the epidemiologic features of
      histoplasmosis, we analyzed deidentified surveillance data for 2011-2014 from the
      following 12 states: Alabama, Arkansas, Delaware, Illinois, Indiana, Kentucky,
      Michigan, Minnesota, Mississippi, Nebraska, Pennsylvania, and Wisconsin. We
      examined epidemiologic and laboratory features and calculated state-specific
      annual and county-specific mean annual incidence rates. A total of 3,409 cases
      were reported. Median patient age was 49 (interquartile range 33-61) years, 2,079
      (61%) patients were male, 1,273 (57%) patients were hospitalized, and 76 (7%)
      patients died. Incidence rates varied markedly between and within states. The
      high hospitalization rate suggests that histoplasmosis surveillance
      underestimates the true number of cases. Improved surveillance standardization
      and surveillance by additional states would provide more comprehensive knowledge
      of histoplasmosis in the United States.

PMID- 29460732
TI  - Emergence of Streptococcus pneumoniae Serotype 12F after Sequential Introduction
      of 7- and 13-Valent Vaccines, Israel.
AB  - Israel implemented use of 7- and 13-valent pneumococcal vaccine in 2009 and 2010,
      respectively. We describe results of prospective, population-based, nationwide
      active surveillance of Streptococcus pneumoniae serotype 12F (Sp12F) invasive
      pneumococcal disease (IPD) dynamics in the 7 years after vaccine introduction. Of
      4,573 IPD episodes during July 2009-June 2016, a total of 434 (9.5%) were caused
      by Sp12F. Sp12F IPD rates (cases/100,000 population) increased in children <5
      years of age, from 1.44 in 2009-2010 to >3.9 since 2011-2012, followed by an
      increase in all ages. During 2011-2016, Sp12F was the most prevalent IPD
      serotype. Sp12F isolates were mostly penicillin nonsusceptible (MIC >0.06 ug/mL;
      MIC50 = 0.12) and predominantly of sequence type 3774), a clone exclusively found
      in Israel (constituting ~90% of isolates in 2000-2009). The sharp increase, long
      duration, and predominance of Sp12F IPD after vaccine implementation reflect a
      single clone expansion and may represent more than a transient outbreak.

PMID- 29460733
TI  - Influenza Vaccination and Incident Tuberculosis among Elderly Persons, Taiwan1.
AB  - Experimental studies have demonstrated that influenza vaccination may protect
      against tuberculosis (TB) through a Th17 response. This nationwide cohort study
      aimed to evaluate the association of influenza vaccination with incident TB among
      elderly persons in Taiwan. This 2005-2012 study included 99,982 elderly persons
      (64,290 vaccinated and 35,692 unvaccinated) from the Taiwan National Health
      Insurance Research Database. During the 738,367 person-years of follow-up, 1,141
      (1.14%) persons had incident TB. The cumulative incidences of TB were 145.2
      cases/100,000 person-years among vaccinated elderly persons and 175.5
      cases/100,000 person-years among unvaccinated elderly persons (p = 0.002). The
      time-dependent Cox proportional hazards model revealed that influenza vaccination
      was an independent protective factor for incident TB. Our results suggest that
      influenza vaccination is associated with a lower risk of incident TB among
      elderly persons in Taiwan. Further investigation of biologic mechanisms is
      warranted.

PMID- 29460734
TI  - Increasing Prevalence of Nontuberculous Mycobacteria in Respiratory Specimens
      from US-Affiliated Pacific Island Jurisdictions1.
AB  - Nontuberculous mycobacteria (NTM) respiratory infections represent a growing
      public health problem in many countries. However, there are limited published
      epidemiologic studies for the Western Pacific region. We reviewed respiratory
      specimens submitted to Diagnostic Laboratory Services in Hawaii, USA, for culture
      of Mycobacterium tuberculosis during August 2007-December 2011 to determine the
      NTM isolation rate. We observed a statistically significant increase in the rate
      of specimens with NTM isolated in respiratory culture (adjusted rate ratio per
      year 1.65, 95% CI 1.54-1.77; p<0.01). In contrast, the number of patients with
      respiratory cultures positive for M. tuberculosis showed no increase (adjusted
      rate ratio per year 0.98, 95% CI 0.94-1.01; p = 0.19). A 6-month subset of NTM
      isolates was identified by using a nucleic acid probe or 16S rRNA sequencing. M.
      avium complex and M. fortuitum were the most common NTM identified.

PMID- 29460735
TI  - Acquired Resistance to Antituberculosis Drugs in England, Wales, and Northern
      Ireland, 2000-2015.
AB  - Among tuberculosis (TB) patients, acquired resistance to anti-TB drugs represents
      a failure in the treatment pathway. To improve diagnosis and care for patients
      with drug-resistant TB, we examined the epidemiology and risk factors associated
      with acquired drug resistance during 2000-2015 among TB patients in England,
      Wales, and Northern Ireland. We found acquired resistance in 0.2% (158/67,710) of
      patients with culture-confirmed TB. Using multivariate logistic regression, we
      identified the following factors associated with acquired drug resistance: having
      pulmonary disease; initial resistance to isoniazid, rifampin, or both; a previous
      TB episode; and being born in China or South Africa. Treatment outcomes were
      worse for patients with than without acquired resistance. Although acquired
      resistance is rare in the study area, certain patient groups are at higher risk.
      Identifying these patients and ensuring that adequate resources are available for
      treatment may prevent acquisition of resistance, thereby limiting transmission of
      drug-resistant strains of mycobacteria.

PMID- 29460737
TI  - Use of Verbal Autopsy to Determine Underlying Cause of Death during Treatment of
      Multidrug-Resistant Tuberculosis, India.
AB  - Of patients with multidrug-resistant tuberculosis (MDR TB), <50% complete
      treatment. Most treatment failures for patients with MDR TB are due to death
      during TB treatment. We sought to determine the proportion of deaths during MDR
      TB treatment attributable to TB itself. We used a structured verbal autopsy tool
      to interview family members of patients who died during MDR TB treatment in India
      during January-December 2016. A committee triangulated information from verbal
      autopsy, death certificate, or other medical records available with the family
      members to ascertain the underlying cause of death. For 66% of patient deaths
      (47/71), TB was the underlying cause of death. We assigned TB as the underlying
      cause of death for an additional 6 patients who died of suicide and 2 of
      pulmonary embolism. Deaths during TB treatment signify program failure;
      accurately determining the cause of death is the first step to designing
      appropriate, timely interventions to prevent premature deaths.

PMID- 29460736
TI  - Epidemiology and Molecular Identification and Characterization of Mycoplasma
      pneumoniae, South Africa, 2012-2015.
AB  - During 2012-2015, we tested respiratory specimens from patients with severe
      respiratory illness (SRI), patients with influenza-like illness (ILI), and
      controls in South Africa by real-time PCR for Mycoplasma pneumoniae, followed by
      culture and molecular characterization of positive samples. M. pneumoniae
      prevalence was 1.6% among SRI patients, 0.7% among ILI patients, and 0.2% among
      controls (p<0.001). Age <5 years (adjusted odd ratio 7.1; 95% CI 1.7-28.7) and
      HIV infection (adjusted odds ratio 23.8; 95% CI 4.1-138.2) among M. pneumonia
      positive persons were associated with severe disease. The detection rate
      attributable to illness was 93.9% (95% CI 74.4%-98.5%) in SRI patients and 80.7%
      (95% CI 16.7%-95.6%) in ILI patients. The hospitalization rate was 28
      cases/100,000 population. We observed the macrolide-susceptible M. pneumoniae
      genotype in all cases and found P1 types 1, 2, and a type 2 variant with
      multilocus variable number tandem repeat types 3/6/6/2, 3/5/6/2, and 4/5/7/2.

PMID- 29460739
TI  - Use of Influenza Risk Assessment Tool for Prepandemic Preparedness.
AB  - In 2010, the Centers for Disease Control and Prevention began to develop an
      Influenza Risk Assessment Tool (IRAT) to methodically capture and assess
      information relating to influenza A viruses not currently circulating among
      humans. The IRAT uses a multiattribute, additive model to generate a summary risk
      score for each virus. Although the IRAT is not intended to predict the next
      pandemic influenza A virus, it has provided input into prepandemic preparedness
      decisions.

PMID- 29460738
TI  - Prospective Observational Study of Incidence and Preventable Burden of Childhood
      Tuberculosis, Kenya.

PMID- 29460740
TI  - Ending the HIV/AIDS Pandemic1.
AB  - The goal of ending the HIV/AIDS pandemic is theoretically achievable and would
      require addressing this global health catastrophe on individual and global levels
      by providing optimal prevention strategies and treatment regimens for individual
      persons living with or at risk for HIV, as well as ending the pandemic as an
      epidemiologic and global health phenomenon. However, from a practical standpoint,
      the pathway to ending the HIV/AIDS pandemic will be difficult and will require
      aggressive implementation of the biomedical research advances that have been made
      in the areas of treatment and prevention; development of additional tools, such
      as a moderately effective HIV vaccine; and attention to critical behavioral and
      social determinants. An end to the HIV/AIDS pandemic can be achieved only with
      provision of sustained and additional resources at the local, regional, national,
      and global levels.

PMID- 29460741
TI  - Coccidioidomycosis Outbreaks, United States and Worldwide, 1940-2015.
AB  - Coccidioidomycosis causes substantial illness and death in the United States each
      year. Although most cases are sporadic, outbreaks provide insight into the
      clinical and environmental features of coccidioidomycosis, high-risk activities,
      and the geographic range of Coccidioides fungi. We identified reports published
      in English of 47 coccidioidomycosis outbreaks worldwide that resulted in 1,464
      cases during 1940-2015. Most (85%) outbreaks were associated with environmental
      exposures; the 2 largest outbreaks resulted from an earthquake and a large dust
      storm. More than one third of outbreaks occurred in areas where the fungus was
      not previously known to be endemic, and more than half of outbreaks involved
      occupational exposures. Coccidioidomycosis outbreaks can be difficult to detect
      and challenging to prevent given the unknown effectiveness of environmental
      control methods and personal protective equipment; therefore, increased awareness
      of coccidioidomycosis outbreaks is needed among public health professionals,
      healthcare providers, and the public.

PMID- 29460742
TI  - Invasive Infections Caused by Nannizziopsis spp. Molds in Immunocompromised
      Patients.
AB  - We report 2 new cases of invasive infections caused by Nannizziopsis spp. molds
      in France. Both patients had cerebral abscesses and were immunocompromised. Both
      patients had recently spent time in Africa.

PMID- 29460743
TI  - Genetic Spatiotemporal Anatomy of Plasmodium vivax Malaria Episodes in Greece,
      2009-2013.
AB  - An influx of immigrants is contributing to the reemergence of Plasmodium vivax
      malaria in Greece; 1 persistent focus of transmission is in Laconia, Peloponnese.
      We genotyped archived blood samples from a substantial proportion of malaria
      cases recorded in Greece in 2009-2013 using 8 microsatellite markers and a PvMSP
      3alpha gene fragment and plotted their spatiotemporal distribution. High parasite
      genetic diversity with low multiplicity of infection was observed. A subset of
      genetically identical/related parasites was restricted to 3 areas in migrants and
      Greek residents, with some persisting over 2 consecutive transmission periods. We
      identified 2 hitherto unsuspected additional foci of local transmission:
      Kardhitsa and Attica. Furthermore, this analysis indicates that several cases in
      migrants initially classified as imported malaria were actually locally acquired.
      This study shows the potential for P. vivax to reestablish transmission and
      counsels public health authorities about the need for vigilance to achieve or
      maintain sustainable malaria elimination.

PMID- 29460744
TI  - Increase in Hospital Admissions for Severe Influenza A/B among Travelers on
      Cruise Ships to Alaska, 2015.
AB  - An increase in hospital admissions for influenza occurred during the summer of
      2015 at an acute care facility in Vancouver, British Columbia, Canada.
      Investigation identified 25 patients with recent history of cruise ship travel to
      Alaska. All characterized influenza A viruses were A(H3N2). We describe patient
      treatment regimens and outcomes.

PMID- 29460745
TI  - Seroprevalence of Dengue and Chikungunya Virus Antibodies, French Polynesia, 2014
      2015.
AB  - We investigated dengue and chikungunya virus antibody seroprevalence in French
      Polynesia during 2014-2015. Dengue virus seroprevalence was ~60% among
      schoolchildren and >83% among the general population; chikungunya virus
      seroprevalence was <3% before and 76% after Zika virus emergence (2013). Dengue
      virus herd immunity may affect Zika virus infection and pathogenesis.

PMID- 29460746
TI  - Global Health Estimate of Invasive Mycobacterium chimaera Infections Associated
      with Heater-Cooler Devices in Cardiac Surgery.
AB  - Investigations of a worldwide epidemic of invasive Mycobacterium chimaera
      associated with heater-cooler devices in cardiac surgery have been hampered by
      low clinical awareness and challenging diagnoses. Using data from Switzerland, we
      estimated the burden of invasive M. chimaera to be 156-282 cases/year in 10 major
      cardiac valve replacement market countries.

PMID- 29460747
TI  - Epidemiology of Recurrent Hand, Foot and Mouth Disease, China, 2008-2015.
AB  - Using China's national surveillance data on hand, foot and mouth disease (HFMD)
      for 2008-2015, we described the epidemiologic and virologic features of recurrent
      HFMD. A total of 398,010 patients had HFMD recurrence; 1,767 patients had 1,814
      cases of recurrent laboratory-confirmed HFMD: 99 reinfections of enterovirus A71
      (EV-A71) with EV-A71, 45 of coxsackievirus A16 (CV-A16) with CV-A16, 364 of other
      enteroviruses with other enteroviruses, 383 of EV-A71 with CV-A16 and CV-A16 with
      EV-A71, and 923 of EV-A71 or CV-A16 with other enteroviruses and other
      enteroviruses with EV-A71 or CV-A16. The probability of HFMD recurrence was 1.9%
      at 12 months, 3.3% at 24 months, 3.9% at 36 months, and 4.0% at 38.8 months after
      the primary episode. HFMD severity was not associated with recurrent episodes or
      time interval between episodes. Elucidation of the mechanism underlying HFMD
      recurrence with the same enterovirus serotype and confirmation that HFMD
      recurrence is not associated with disease severity is needed.

PMID- 29460748
TI  - Drug Resistance of Mycobacterium tuberculosis Complex in a Rural Setting, Angola.
AB  - We found high prevalence rates of multidrug-resistant tuberculosis among
      retreatment patients (71.1%) and persons with new cases (8.0%) in Angola. These
      findings are of concern but should be interpreted with caution. A national drug
      resistance survey is urgently needed to determine the actual prevalence of
      multidrug-resistant tuberculosis in Angola.

PMID- 29460749
TI  - Statistical Method to Detect Tuberculosis Outbreaks among Endemic Clusters in a
      Low-Incidence Setting.
AB  - We previously reported use of genotype surveillance data to predict outbreaks
      among incident tuberculosis clusters. We propose a method to detect possible
      outbreaks among endemic tuberculosis clusters. We detected 15 possible outbreaks,
      of which 10 had epidemiologic data or whole-genome sequencing results. Eight
      outbreaks were corroborated.

PMID- 29460750
TI  - Whole-Genome Analysis of Mycobacterium tuberculosis from Patients with
      Tuberculous Spondylitis, Russia.
AB  - Whole-genome analysis of Mycobacterium tuberculosis isolates collected in Russia
      (N = 71) from patients with tuberculous spondylitis supports a detailed
      characterization of pathogen strain distributions and drug resistance phenotype,
      plus distinguished occurrence and association of known resistance mutations. We
      identify known and novel genome determinants related to bacterial virulence,
      pathogenicity, and drug resistance.

PMID- 29460751
TI  - Mycobacterium avium subsp. hominissuis Infection in a Domestic Rabbit, Germany.
AB  - Mycobacterium avium subsp. hominissuis is an opportunistic pathogen present in
      soil and dust. We report M. avium subsp. hominissuis infection found in a
      domestic rabbit in Hannover, Germany, in May 2017.

PMID- 29460752
TI  - Introduction of the Anopheles bancroftii Mosquito, a Malaria Vector, into New
      Caledonia.
AB  - In June 2017, an Anopheles mosquito species was detected in New Caledonia.
      Morphologic identification and genomic sequencing revealed that the specimens
      tested belong to An. bancroftii genotype A1. This introduction underscores the
      risk for local malaria transmission and the vulnerability of New Caledonia to
      vector introduction.

PMID- 29460753
TI  - Fishborne Zoonotic Trematodes Transmitted by Melanoides tuberculata Snails, Peru.
AB  - We investigated the transmission of the fishborne trematodes Centrocestus
      formosanus and Haplorchis pumilio by Melanoides tuberculata snails in Peru. We
      report on results of experimental, morphological, and molecular approaches and
      discuss the potential risk for future human cases, given the existence of food
      habits in the country involving the ingestion of raw fish.

PMID- 29460754
TI  - Delftia tsuruhatensis, an Emergent Opportunistic Healthcare-Associated Pathogen.
AB  - Delftia tsuruhatensis, which was first isolated in environmental samples, was
      rarely associated with human infections. We report on pneumonia caused by D.
      tsuruhatensis in an infant who underwent cardiac surgery. Retrospective analyses
      detected 9 other isolates from 8 patients. D. tsuruhatensis is an emergent
      pathogen, at least for immunocompromised patients.

PMID- 29460755
TI  - Severe Pneumonia Caused by Toxigenic Corynebacterium ulcerans Infection, Japan.
AB  - Corynebacterium ulcerans infection was recently recognized as a zoonosis. We
      present 2 cases of severe pneumonia complicated by diffuse pseudomembrane
      formation on the bronchus caused by C. ulcerans-producing diphtheria toxin. Our
      purpose is to alert medical professionals to the virulence of Corynebacterium
      species other than C. diphtheriae.

PMID- 29460756
TI  - Characteristics Associated with Negative Interferon-gamma Release Assay Results
      in Culture-Confirmed Tuberculosis Patients, Texas, USA, 2013-2015.
AB  - Interferon-gamma release assays (IGRAs) are the preferred diagnostic test for
      tuberculosis (TB) infection in at-risk populations in developed countries.
      However, IGRAs have high false-negative rates in patients with TB disease.
      Population-based studies assessing the factors associated with negative IGRA
      results in TB patients have not been performed. Using statewide TB surveillance
      data of culture-confirmed TB patients in Texas, USA, during 2013-2015, we
      describe the patient characteristics and treatment outcomes associated with false
      negative IGRA results. Among 2,854 TB patients, 1,527 (53.5%) had an IGRA result;
      97.4% (1,487/1,527) of those had a positive (87.7%) or negative (12.3%) result.
      Older age, HIV co-infection, non-Hispanic white race/ethnicity, and being tested
      with T-SPOT.TB were associated with negative IGRA results. TB patients with
      negative IGRA results had a higher mortality, potentially due to delayed
      treatment. Healthcare providers should consider these risk factors when making
      decisions for patients with suspected TB and negative IGRA results and
      potentially provide treatment.

PMID- 29460757
TI  - Acetobacter indonesiensis Pneumonia after Lung Transplantation.
AB  - We report a case of Acetobacter indonesiensis pneumonia in a 51-year-old woman
      after bilateral lung transplantation. We found 2 other A. indonesiensis pneumonia
      cases reported in the literature. All 3 cases involved complex patients exposed
      to broad-spectrum antimicrobial drugs, suggesting that this pathogen may be
      opportunistic and highly drug-resistant.

PMID- 29460758
TI  - New Lineage of Lassa Virus, Togo, 2016.
AB  - We describe a strain of Lassa virus representing a putative new lineage that was
      isolated from a cluster of human infections with an epidemiologic link to Togo.
      This finding extends the known range of Lassa virus to Togo.

PMID- 29460759
TI  - Molecular and Epidemiologic Analysis of Reemergent Salmonella enterica Serovar
      Napoli, Italy, 2011-2015.
AB  - Human infections with Salmonella enterica serovar Napoli are uncommon in Europe.
      However, these infections represented 5.9% of salmonellosis cases in Italy during
      2014-2015. The source of infection is unknown. We analyzed surveillance data and
      compared strain genetic similarities and found that contaminated vegetables and
      surface water are probable sources of human infection.

PMID- 29460760
TI  - Artificial Differences in Clostridium difficile Infection Rates Associated with
      Disparity in Testing.
AB  - In 2015, Clostridium difficile testing rates among 30 US community,
      multispecialty, and cancer hospitals were 14.0, 16.3, and 33.9/1,000 patient
      days, respectively. Pooled hospital onset rates were 0.56, 0.84, and 1.57/1,000
      patient-days, respectively. Higher testing rates may artificially inflate
      reported rates of C. difficile infection. C. difficile surveillance should
      consider testing frequency.

PMID- 29460761
TI  - Evidence for Previously Unidentified Sexual Transmission of Protozoan Parasites.
AB  - Knowing the mode of transmission of a disease can affect its control and
      prevention. Here, we identify 5 protozoan parasites with demonstrated presence in
      seminal fluid, only 1 of which has been identified as a sexually transmitted
      disease among humans.

PMID- 29460763
TI  - Roles of Graphic Pathographies in Clinical Training.
AB  - Although graphic pathographies have recently been recognized as playing an
      important role in medical care, they have not been formally incorporated in many
      medical school curricula. In this paper, I discuss current applications of
      graphic pathographies in medicine as well as some potential ethical and
      epistemological challenges that can arise when using these narratives. Health
      professionals and medical educators should understand when, why, and how to use
      graphic pathographies with the goal of enhancing medical education and patient
      care.

PMID- 29460762
TI  - Cache Valley Virus in Aedes japonicus japonicus Mosquitoes, Appalachian Region,
      United States.
AB  - We detected Cache Valley virus in Aedes japonicus, a widely distributed invasive
      mosquito species, in an Appalachian forest in the United States. The forest
      contained abundant white-tailed deer, a major host of the mosquito and virus.
      Vector competence trials indicated that Ae. j. japonicus mosquitoes can transmit
      this virus in this region.

PMID- 29460764
TI  - Representations of Patients' Experiences of Autonomy in Graphic Medicine.
AB  - I advocate using graphic medicine in introductory medical ethics courses to help
      trainees learn about patients' experiences of autonomy. Graphic narratives about
      this content offer trainees opportunities to gain insights into making diagnoses
      and recommending treatments. Graphic medicine can also illuminate aspects of
      patients' experiences of autonomy differently than other genres. Specifically,
      comics allow readers to consider visual and text-based representations of a
      patient's actions, speech, thoughts, and emotions. Here, I use Ellen Forney's
      Marbles: Mania, Depression, Michelangelo, and Me: A Graphic Memoir and Peter
      Dunlap-Shohl's My Degeneration: A Journey Through Parkinson's as two examples
      that can serve as pedagogical resources.

PMID- 29460765
TI  - Are Comic Books Appropriate Health Education Formats to Offer Adult Patients?
AB  - Physicians who recommend patient education comics should consider that some
      patients might question the appropriateness of this format, especially in the US,
      where a dominant cultural view of comics is that they are juvenile and intended
      to be funny. In this case, Dr. S might have approached communication with Mrs. T
      differently, even without knowing her attitude toward comics as a format for
      delivering health information. Dr. S could acknowledge that though some people
      might not expect useful medical information in a comic format, it has unique
      aspects and new research on patient education comics shows that even adults are
      finding this medium to be effective, educational, and engaging. Offering comics
      to patients, however, does potentially require patient educators to invest
      additional time to review and assess their accuracy and relevance.

PMID- 29460766
TI  - Go Home, Med Student: Comics as Visual Media for Students' Traumatic Medical
      Education Experiences.
AB  - A comic created by a medical student allows the reader to share the student's own
      unique perception of the medical education experience. Through the process of
      comic creation, medical students have opportunities to gain insight into how
      their relationships with patients and supervising physicians have shaped the
      physician they will become. The comic itself can be a safe space for expression
      and provides an opportunity for students and educators to share experiences.

PMID- 29460767
TI  - How Should a Stigmatized Diagnosis Be Conveyed? How What Went Wrong Is
      Represented in Swallow Me Whole.
AB  - This essay considers the ethical problems raised by a scene of diagnosis
      presentation in Nate Powell's graphic novel Swallow Me Whole, in which the
      patient is not only not engaged by the physician, but also effectively
      marginalized from the moment that her condition is named and medicalized. Put in
      the context of the book as a whole and in relationship to the unique affordances
      of the comics form, however, we see that though the physician made a correct
      diagnosis, the case did not end well due to the poor delivery of that diagnosis
      and the lack of support from members of the patient's extended community.

PMID- 29460768
TI  - Teaching Confidentiality through Comics at One Spanish Medical School.
AB  - At the University of Zaragoza in Spain we developed an innovative way to teach
      the concept of confidentiality to medical students, which we tested by comparing
      the use of customized comics with more traditional methods. We proved that using
      comics is more attractive to students than lectures and class discussions, that
      it increases class participation and students' self-awareness of learning, and
      that it maintains the same academic results. We share our experience visually in
      a two-page comic.

PMID- 29460769
TI  - Graphic Pathographies and the Ethical Practice of Person-Centered Medicine.
AB  - Graphic medicine is a swiftly growing movement that explores, theoretically and
      practically, the use of comics in medical education and patient care. At the
      heart of graphic medicine are graphic pathographies, stories of illness conveyed
      in comic form. These stories are helpful tools for health care professionals who
      seek new insight into the personal, lived experience of illness and for patients
      who want to learn more about their disease from others who have actually
      experienced it. Featuring excerpts from five graphic pathographies, this essay
      illustrates how the medium can be used to educate patients and enhance empathy in
      health care professionals, particularly with regard to informed consent and end
      of-life issues.

PMID- 29460770
TI  - Parasites! Graphic Exploration of Tropical Disease Drug Development.
AB  - Parasites!, a 2010 comic sponsored by the Wellcome Trust Centre for Molecular
      Parasitology, demonstrates that a graphic narrative can play a role in energizing
      public debate. Part of the genre known as graphic medicine-comics about illness,
      treatment, disability, and caregiving-Parasites! is intended to educate readers
      of all ages about illnesses less known in the developed world. Two visual
      strategies in particular enable the comic to offer an alternative and aesthetic
      response to questions about developing drugs to treat tropical diseases for
      profit. By including visuals and text, and not just one of these formats, viewers
      must reorient themselves aesthetically and epistemologically to ethical, social,
      cultural, and political structures that adversely affect human health.

PMID- 29460771
TI  - How Should We Judge the Ethics of Illustrations in Graphic Medicine Novels?
AB  - This essay argues that we should judge the illustrations in a graphic novel
      (often a memoir) in the context of the entire work. Judging a work on its emotive
      effects and the values it expresses, we can consider the ways a graphic novel
      represents the experience of illness, disability, or injury.

PMID- 29460772
TI  - Of Cornopleezeepi and Party Poopers: A Brief History of Physicians in Comics.
AB  - The representations of physicians and medical practice found in comic strips,
      comic books, and graphic novels throughout the past century reflect broader
      representational trends in popular visual media. Drawing on examples including
      Winsor McCay's Dream of the Rarebit Fiend, the superhero comics character Stephen
      Strange/Doctor Strange, and contemporary graphic medicine, this article outlines
      the shifting models for depicting physicians and medical ethics in comics. It
      concludes that contemporary representations are often more realistic and nuanced,
      although gender and racial diversity along with diversity in medical
      specializations remains problematic.

PMID- 29460773
TI  - The Crisis in Our Neighborhood.
AB  - This comic represents various clinical and ethical dimensions of the skyrocketing
      incidence of opioid overdose. The comic also seeks to represent the humanity of
      patients struggling with addiction and to highlight the importance of clinicians'
      roles in helping mitigate the harms of opioid dependence.

PMID- 29460774
TI  - Reviewing Systems.
AB  - This poster represents the experience of a clinician-in-training with a
      diagnostic screening method typically called "review of systems." Although at
      times executing this method can feel onerous, it is intended to reveal key
      symptoms, promote inquiry, and enhance communication. It also sometimes generates
      unexpected and important insights, and that experience is conveyed here with a
      combination of text and images.

PMID- 29460775
TI  - Representing AIDS in Comics.
AB  - Matthew P. McAllister wrote: "Comic books can and have contributed positively to
      the discourse about AIDS: images that encourage true education, understanding and
      compassion can help cope with a biomedical condition which has more than a
      biomedical relevance" [1]. With this in mind, I combined a 23-narrator oral
      history and my personal memoir about an inpatient Chicago AIDS hospital unit in
      my book, Taking Turns: Stories from HIV/AIDS Care Unit 371. In doing so, I built
      upon the existing rich history of HIV/AIDS in comics, which this article will
      briefly describe. Although not a comprehensive review of the intersection of AIDS
      and comics, the book is a tour through influences that proved useful to me. In
      addition, in making my book, I faced a distinct ethical issue with regard to
      representing patient experiences with HIV/AIDS, and I describe here how I
      addressed it.

PMID- 29460776
TI  - Preserving neuromuscular synapses in ALS by stimulating MuSK with a therapeutic
      agonist antibody.
AB  - In amyotrophic lateral sclerosis (ALS) and animal models of ALS, including SOD1
      G93A mice, disassembly of the neuromuscular synapse precedes motor neuron loss
      and is sufficient to cause a decline in motor function that culminates in lethal
      respiratory paralysis. We treated SOD1-G93A mice with an agonist antibody to
      MuSK, a receptor tyrosine kinase essential for maintaining neuromuscular
      synapses, to determine whether increasing muscle retrograde signaling would slow
      nerve terminal detachment from muscle. The agonist antibody, delivered after
      disease onset, slowed muscle denervation, promoting motor neuron survival,
      improving motor system output, and extending the lifespan of SOD1-G93A mice.
      These findings suggest a novel therapeutic strategy for ALS, using an antibody
      format with clinical precedence, which targets a pathway essential for
      maintaining attachment of nerve terminals to muscle.

PMID- 29460777
TI  - Confirmation for conformational selection.
AB  - NMR studies settle part of a long-standing debate about the mechanism used by the
      Hsp70 chaperone to recognize substrates.

PMID- 29460778
TI  - Conserved conformational selection mechanism of Hsp70 chaperone-substrate
      interactions.
AB  - Molecular recognition is integral to biological function and frequently involves
      preferred binding of a molecule to one of several exchanging ligand conformations
      in solution. In such a process the bound structure can be selected from the
      ensemble of interconverting ligands a priori (conformational selection, CS) or
      may form once the ligand is bound (induced fit, IF). Here we focus on the
      ubiquitous and conserved Hsp70 chaperone which oversees the integrity of the
      cellular proteome through its ATP-dependent interaction with client proteins. We
      directly quantify the flux along CS and IF pathways using solution NMR
      spectroscopy that exploits a methyl TROSY effect and selective isotope-labeling
      methodologies. Our measurements establish that both bacterial and human Hsp70
      chaperones interact with clients by selecting the unfolded state from a pre
      existing array of interconverting structures, suggesting a conserved mode of
      client recognition among Hsp70s and highlighting the importance of molecular
      dynamics in this recognition event.

PMID- 29460779
TI  - Impact of the scale-up of piped water on urogenital schistosomiasis infection in
      rural South Africa.
AB  - Recent work has estimated that sub-Saharan Africa could lose US$3.5 billion of
      economic productivity every year as a result of schistosomiasis and soil
      transmitted helminthiasis. One of the main interventions to control
      schistosomiasis is the provision of safe water to limit the contact with infected
      water bodies and break the cycle of transmission. To date, a rigorous
      quantification of the impact of safe water supplies on schistosomiasis is
      lacking. Using data from one of Africa's largest population-based cohorts, we
      establish the impact of the scale-up of piped water in a typical rural South
      African population over a seven-year time horizon. High coverage of piped water
      in the community decreased a child's risk of urogenital schistosomiasis infection
      eight-fold (adjusted odds ratio = 0.12, 95% CI 0.06-0.26, p<0.001). The provision
      of safe water could drive levels of urogenital schistosomiasis infection to low
      levels of endemicity in rural African settings.

PMID- 29460781
TI  - The burden and nature of malnutrition among patients in regional hospital
      settings: A cross-sectional survey.
AB  - BACKGROUND/AIMS: Indigenous people experience a higher burden of nutrition
      related conditions and are more likely to experience food insecurity compared to
      non-Indigenous people. Consequently, they remain at increased risk of
      malnutrition; particularly when residing in regional or remote areas. This study
      aims to compare and characterise the burden and nature of malnutrition among a
      representative cohort of Indigenous and non-Indigenous Australians admitted to
      regional hospitals for medical inpatient care. METHODS: This was a cross
      sectional survey conducted in three regional hospitals in the Northern Territory
      and Far North Queensland of Australia from February 2015 to September 2015. A
      total of 1606 adult medical inpatients were screened for eligibility. Of these,
      608 eligible patients were screened for malnutrition using the validated
      Malnutrition Screening Tool and assessed for malnutrition using the Subjective
      Global Assessment. Socio-economic and health-related variables and anthropometric
      measurements were collected to identify the correlates of malnutrition. RESULTS:
      Of the 271 Indigenous patients and 337 non-Indigenous patients screened and
      assessed for malnutrition, 250/608 (41.7%, 95% CI 40.1-52.3%) were found to be
      malnourished. Significantly higher rates of malnutrition (46.1%, 95% CI 40.1
      52.3% versus 37.1%, 95% CI 31.9-42.5%) were found in Indigenous patients compared
      to non-Indigenous patients (P = 0.024). Higher rates of malnutrition were
      observed in Indigenous patients residing in Central Australia (56.7%, 95% CI 46.7
      66.4%) than in the Top End of the Northern Territory (40.7%, 95% CI 31.7-50.1%)
      and in Far North Queensland (36.7%, 95% CI 23.4-51.7%). Factors independently
      predictive of malnutrition for both Indigenous and non-Indigenous participants
      included residence in Central Australia (OR 4.31, 95% CI 2.63-7.90, P < 0.001);
      an increased Charlson Comorbidity Index prognostic score (OR 1.37 [per
      incremental score], 95% CI 1.19-1.59, P < 0.001); and an underweight Body Mass
      Index (OR 29.97, 95% CI 3.68-244.0, P < 0.001). Of the 250/608 patients who were
      malnourished, the positive predictor value (PPV) for malnourished patients who
      were underweight was 96.6% (95% CI 88.3-99.6%); for Indigenous Australians who
      were malnourished and underweight, the PPV was 100%. A mid-upper arm
      circumference of less than 23 cm demonstrated a strong PPV for all patients who
      were malnourished (96.1%, 95% CI 89.0-99.2%). CONCLUSION: This is the first study
      to characterise malnutrition in adult Indigenous Australians in a hospital
      inpatient setting. Compared to non-Indigenous patients the burden and pattern of
      malnutrition was both higher and markedly different among Indigenous patients.
      These data highlight the critical importance for actively screening for and
      responding to malnutrition in this vulnerable patient population in regional and
      remote settings.

PMID- 29460780
TI  - 3.3-A resolution cryo-EM structure of human ribonucleotide reductase with
      substrate and allosteric regulators bound.
AB  - Ribonucleotide reductases (RNRs) convert ribonucleotides into
      deoxyribonucleotides, a reaction essential for DNA replication and repair. Human
      RNR requires two subunits for activity, the alpha subunit contains the active
      site, and the beta subunit houses the radical cofactor. Here, we present a 3.3-A
      resolution structure by cryo-electron microscopy (EM) of a dATP-inhibited state
      of human RNR. This structure, which was determined in the presence of substrate
      CDP and allosteric regulators ATP and dATP, has three alpha2 units arranged in an
      alpha6 ring. At near-atomic resolution, these data provide insight into the
      molecular basis for CDP recognition by allosteric specificity effectors dATP/ATP.
      Additionally, we present lower-resolution EM structures of human alpha6 in the
      presence of both the anticancer drug clofarabine triphosphate and beta2.
      Together, these structures support a model for RNR inhibition in which beta2 is
      excluded from binding in a radical transfer competent position when alpha exists
      as a stable hexamer.

PMID- 29460782
TI  - Dietary acid load and risk of type 2 diabetes: A systematic review and dose
      response meta-analysis of prospective observational studies.
AB  - BACKGROUND & AIMS: Existing evidence suggests a link between acid-forming
      potential of diet and type 2 diabetes. But the degree of the associations and
      shape of the dose-response relations across different indices of diet-dependent
      acid load and risk of type 2 diabetes and potential confounding by sex have not
      been established. We aimed to test the dose-response association of different
      measures of dietary acid load and risk of incident type 2 diabetes, with
      considering the sex as a potential confounder. METHODS: Systematic search was
      done using PubMed and Scopus, from inception up to September 2017. Prospective
      observational studies reporting the risk estimates of type 2 diabetes for three
      or more quantitative categories of potential renal acid load (PRAL), net
      endogenous acid production (NEAP) and animal protein-to-potassium ratio (A:P)
      scores were included. Pooled relative risks (RRs) were calculated using random
      effects models. RESULTS: Seven prospective cohort studies with 319,542
      participants and 17,986 incident cases of type 2 diabetes were included. Pooled
      RRs for a 5 unit increment in dietary PRAL, NEAP and A:P was 1.04 (95% CI: 1.01,
      1.06; I2 = 79%, n = 7), 1.03 (95% CI: 1.01, 1.04; I2 = 54%, n = 7), and 1.11 (95%
      CI: 1.07, 1.15; I2 = 41%, n = 3), respectively. Subgroup analysis resulted in
      significant positive relationship only among women, compared with men. There was
      a linear association between NEAP and A:P scores and risk of type 2 diabetes,
      whereas the association appeared to be U-shaped in analysis of PRAL. CONCLUSIONS:
      Adherence to a diet with high acid-forming potential might increase the risk of
      type 2 diabetes. Shape of the dose-response relations across different indices of
      dietary acid load and potential sex differences in the associations need to be
      further explored. The interpretation of the results is limited by low number of
      studies.

PMID- 29460783
TI  - Zusto: A new sweetening agent with low glycemic index.
AB  - BACKGROUND & AIMS: Sweetening agents are sugar substitutes with a low glycemic
      index, used to obtain a better glycemic control in diabetes patients. However,
      they also may have a role in other subjects, as a high glycemic index is thought
      to cause many pathological conditions. Unfortunately, not all artificial
      sweeteners are perceived as sweet as sugar by patients. Consumers refer often to
      an after taste present in foods sweetened with intensive sweeteners. The
      objective of this study was to explore whether Zusto(r) had a low glycemic index,
      to replace glucose as a sweetener. METHODS: In this study, the glycemic index
      (GI) of a new sweetening agent, Zusto(r), is compared to that of glucose 25 g, a
      standard sugar-loaded drink used in the oral glucose tolerance test to detect
      diabetes, as primary endpoint. Zusto(r) is composed of non-digestible, water
      soluble fibers and sweeteners. 10 healthy, female non-obese volunteers received
      glucose and Zusto(r), albeit by an interval of a week. Evolution of glycemia, C
      peptide and insulin release was measured at different time-points after intake.
      RESULTS: The results show that, when calculating the mean incremental Area Under
      the Curve (AUC), the AUC of glucose was around five times as high as that of
      Zusto(r); a GI of 22 for Zusto(r) was calculated. Furthermore, Zusto(r) had no
      significant effect on the glycemia, contrary to glucose, for at least 60'. This
      was also the case concerning C-peptide and insulin release, but the difference
      lasted even for 180'. Moreover, Zusto(r) was perceived as sweet by all
      volunteers, with no particular aftertaste. CONCLUSION: Zusto(r) could be a viable
      alternative for fast sugars and other sweetening agents, both for diabetic
      patients and other subjects, requiring however a larger trial to confirm these
      results. CLINICALTRIALS.GOV: NCT02607345.

PMID- 29460784
TI  - Erythrocyte membrane saturated fatty acids profile in newly diagnosed Basal Cell
      Carcinoma patients.
AB  - BACKGROUND: Skin cancers are the most prevalent malignancy worldwide and Basal
      Cell Carcinoma (BCC) include the major type of nonmelanoma skin cancers. Fatty
      acids (FA) have a structural role in cell membranes and play an important role
      for many physiological and pathological immunologic pathways. Several prospective
      studies have been conducted on circulating fatty acids and the risk of prostate,
      breast and other cancers. The present study aimed to determine the saturated
      fatty acid composition differences of red blood cells (RBCs) in BCC patients and
      healthy control. METHODS: A hospital-based case-control study was conducted on
      new cases diagnosed of BCC patients. All subjects completed dietary recalls for
      dietary assessment. After fatty acids extraction, purification and preparation,
      gas chromatography was performed. The results were expressed in relative values
      (percent). RESULTS: Cases had lower RBC levels of Caproic acid (6:0) (P < 0.001),
      Caprylic acid (8:0) (P = 0.01), Capric acid (10:0) (P = 0.01), Palmitic acid
      (16:0) (P = 0.02) and higher RBC level of Pentadecanoic acid (15:0) (P = 0.04)
      and Stearic acid (18:0) (P = 0.01) compared with controls but did not differ in
      the level of the other primary saturated fatty acids. Saturation Index as defined
      by Stearic to Oleic acid ratio was significantly lower in BCC patients in
      comparison with Control group (P = 0.02). CONCLUSION: Here we showed that BCC
      patient had considerable differences in the SFA profiles in comparison with
      healthy subjects.

PMID- 29460785
TI  - The association between nutritional status and frailty characteristics among
      geriatric outpatients.
AB  - BACKGROUND: Frailty is a common clinical syndrome in older adults and is
      associated with an increased risk of poor health outcomes, e.g. falls,
      disability, hospitalization, and mortality. Nutritional status might be an
      important factor contributing to frailty. This study aims to describe the
      association between nutritional status and characteristics of frailty in patients
      attending a geriatric outpatient clinic. METHODS: Clinical data was collected of
      475 patients who visited the geriatric outpatient department of a Dutch hospital
      between 2005 and 2010. Frailty was determined by: incontinence, Activities of
      Daily Living (ADL), Instrumental Activities of Daily Living (IADL), mobility,
      Geriatric Depression Scale (GDS) and Mini Mental State Exam (MMSE). Nutritional
      status was represented by the Mini Nutritional Assessment (MNA) and plasma
      concentrations of several micronutrients, whereby MNA< 17 indicated malnutrition
      and MNA 17-23.5 indicated risk of malnutrition. 'More frail' patients (>=3
      frailty characteristics) were compared to 'less frail' patients (<3 frailty
      characteristics) with logistic regression analyses, adjusted for age, sex and
      other important covariates. RESULTS: Of 404 patients with complete data, mean age
      (SD) was 80 (7) years and 34% was male. Prevalence of 'more frail' patients was
      47%. Prevalence of malnutrition and risk of malnutrition was 16% and 56%
      respectively. Malnutrition and risk of malnutrition were both independently
      related to being 'more frail', with ORs (95% CI) of 8.1 [3.5-18.8] and 3.1 [1.7
      5.5] respectively. This association was driven by functional decline (ADL, IADL
      and mobility) and depression (GDS), but not by cognitive impairment (MMSE). None
      of the micronutrient plasma concentrations were related to frailty. CONCLUSION:
      In geriatric outpatients, malnutrition is independently related to having >=3
      frailty characteristics. Assessing nutritional status could prove usefulness in
      early clinical detection and prevention of frailty.

PMID- 29460786
TI  - Appropriateness of peripheral parenteral nutrition use in adult patients at an
      academic medical center.
AB  - BACKGROUND & AIMS: Current evidence and guidelines identify patient populations
      who may benefit from parenteral nutrition. Peripheral parenteral nutrition (PPN)
      may be indicated for a subset of patients; however, PPN therapy carries a risk of
      associated adverse effects. The purpose of this project was to assess
      appropriateness of current PPN prescribing practices at an academic medical
      center to determine whether additional guidance and oversight may be beneficial.
      METHODS: Adult patients admitted from August 1, 2015 to November 30, 2015 with at
      least one order of PPN administered were included. PPN use was evaluated for
      appropriateness using definitions derived from clinical practice guidelines and
      standard of practice. Adverse events, including phlebitis and bacteremia, were
      also examined. RESULTS: Of the 159 patients included, 51 (32.1%) received
      appropriate PPN therapy, in which all four criteria for appropriateness were met.
      In regards to the criteria for appropriateness, 128 (80.5%) had an appropriate
      indication, 85 (53.5%) had appropriate time to PPN initiation, 157 (98.7%) had an
      appropriate duration of therapy, and 112 (70.4%) achieved an appropriate
      percentage of goal daily calories. In terms of complications associated with PPN
      therapy, 69 (43.4%) patients had documented phlebitis and bacteremia occurred in
      5 (3.1%) of the patients. CONCLUSION: During the study period, PPN was
      appropriately utilized in only one-third of patients and phlebitis occurred in
      almost half of all patients. Restrictions on PPN prescribing may allow nutrition
      support clinicians to prospectively evaluate patients to optimize nutrition
      therapy and minimize the incidence of inappropriate PPN use.

PMID- 29460787
TI  - Accuracy of the visual estimation method as a predictor of food intake in
      Alzheimer's patients provided with different types of food.
AB  - BACKGROUND & AIMS: The visual estimation method is commonly used in hospitals and
      other care facilities to evaluate food intake through estimation of plate waste.
      In Japan, no previous studies have investigated the validity and reliability of
      this method under the routine conditions of a hospital setting. The present study
      aimed to evaluate the validity and reliability of the visual estimation method,
      in long-term inpatients with different levels of eating disability caused by
      Alzheimer's disease. The patients were provided different therapeutic diets
      presented in various food types. METHODS: This study was performed between
      February and April 2013, and 82 patients with Alzheimer's disease were included.
      Plate waste was evaluated for the 3 main daily meals, for a total of 21 days, 7
      consecutive days during each of the 3 months, originating a total of 4851 meals,
      from which 3984 were included. Plate waste was measured by the nurses through the
      visual estimation method, and by the hospital's registered dietitians through the
      actual measurement method. The actual measurement method was first validated to
      serve as a reference, and the level of agreement between both methods was then
      determined. The month, time of day, type of food provided, and patients' physical
      characteristics were considered for analysis. RESULTS: For the 3984 meals
      included in the analysis, the level of agreement between the measurement methods
      was 78.4%. Disagreement of measurements consisted of 3.8% of underestimation and
      17.8% of overestimation. Cronbach's alpha (0.60, P < 0.001) indicated that the
      reliability of the visual estimation method was within the acceptable range.
      CONCLUSION: The visual estimation method was found to be a valid and reliable
      method for estimating food intake in patients with different levels of eating
      impairment. The successful implementation and use of the method depends upon
      adequate training and motivation of the nurses and care staff involved.

PMID- 29460788
TI  - Metabolic syndrome among rural Indian adults.
AB  - BACKGROUND & AIMS: To prevent an increasing level of mortality due to type 2
      diabetes mellitus and cardiovascular disease among the rural Indian population, a
      management strategy of the metabolic syndrome (MetS) should be devised. This
      study aims to estimate the burden of MetS and its associated risk factors.
      METHODS: Data from the Birbhum Population Project covering 9886 individuals (4810
      male and 5076 female population) aged >=18 years were used. The burden of
      metabolic syndrome, as defined by the Third Report of the National Cholesterol
      Education Program Adult Treatment Panel, was determined. Bivariate and
      multivariate (logistic regression) analyses were used to attain the study
      objective. RESULTS: Over 10.7% of the males and 20.3% of the females were
      diagnosed with MetS. Irrespective of sex, older individuals, being
      overweight/obese (body mass index of >=23 kg/m2) had higher probability of
      developing MetS, whereas being underweight is deemed a protective factor against
      MetS. Low physical activity among women appeared to be a risk factor for MetS.
      CONCLUSION: The prevalence of MetS is concerning even in rural India. Any
      intervention designed to address the issue could emphasize on weight loss, and
      physical activity, focusing on women and people at an advanced stage of life.

PMID- 29460789
TI  - Percutaneous endoscopic gastrostomy (PEG) versus radiologically inserted
      gastrostomy (RIG): A comparison of outcomes at an Australian teaching hospital.
AB  - OBJECTIVE: Gastrostomy tubes for enteral nutrition are most commonly inserted via
      percutaneous endoscopic gastrostomy (PEG) or radiologically inserted gastrostomy
      (RIG) techniques. The current study aimed to compare clinical outcomes and
      complication rates in patients who underwent PEG and RIG procedures at a tertiary
      teaching hospital in Australia. METHODS: A retrospective review was conducted on
      patients who underwent PEG or RIG tube insertion between February 2013 and
      February 2015 at Flinders Medical Centre, Australia. The primary outcome studied
      was the tube dislodgement rate. Secondary outcomes measured included hospital
      length of stay, 30 day and 1 year mortality and peri- and post-procedural
      complications such as hypoxia, bleeding, stoma site infection and haematoma.
      Baseline comparisons were conducted using the Mann-Whitney test and chi square
      test. RESULTS: 137 patients (PEG = 85, RIG = 52) underwent gastrostomy tube
      insertion. Indications for insertion were head and neck cancer (PEG = 30, RIG =
      21), stroke (PEG = 27, RIG = 11), post-trauma (PEG = 6, RIG = 3) and
      neuromuscular pathologies (PEG = 9, RIG = 0). There was a significantly higher
      tube dislodgement rate in RIG (26.5%) compared to PEG (2.4%), p < 0.001. The 1
      year mortality was also significantly higher after RIG (46.2%) compared to the
      PEG group (16.7%), p < 0.05. No differences were seen in other peri- and post
      procedural complications. CONCLUSION: Although both PEG and RIG insertion
      techniques compare favourably in terms of the majority of peri and post
      procedural complications, the rates of tube dislodgement were significantly
      higher in the RIG group. The higher mortality rate at 1 year after RIG placement
      may be related to patient selection particularly as no differences were seen at
      30 days.

PMID- 29460790
TI  - Protein and micronutrient deficiencies in patients with radiation cystitis and
      outcome after hyperbaric oxygen therapy.
AB  - BACKGROUND & AIMS: Haemorrhagic radiation cystitis (HRC) is a late complication
      of pelvic radiotherapy. Severe cases are difficult to treat due to persistent or
      recurrent bleeding, despite urological and hyperbaric oxygen therapy (HBOT).
      However, wound healing requires a good nutritional status. In this respect, we
      aimed at analysing the nutritional status of patients with HRC prior to the onset
      of HBOT and at highlighting predictive nutritional factors of outcome. METHODS:
      Data were retrospectively collected from a cohort of 179 patients with HRC
      (between 2011 and 2015). Haematuria was graded according to the Subjective,
      Objective, Management, Analytic scale (SOMA): grade-4 (n = 46) was compared with
      grade-3 (n = 56), and with grades 1 and 2 (n = 77). S-albumin, prealbumin,
      vitamins C, D and B6, zinc, selenium, and essential fatty acids were evaluated
      before HBOT. HBOT response was measured at 3 months according to the haematuria
      SOMA grade. The Mann-Whitney test, Fisher's exact test and principal-component
      analysis were used to compare groups. RESULTS: Patients with higher haematuria
      grades (3 and 4) harboured significant deficiencies in S-albumin, prealbumin,
      vitamins C, D and B6, zinc, selenium and essential fatty acids. Moreover, grade-4
      patients without improvement after 3 months of HBOT had significant lower initial
      levels of S-albumin, vitamin C, selenium and linoleic acid. Vitamin C levels <2.5
      mg/L were strongly associated with HBOT non-response (OR 23.14, 95% CI 3.73
      143.69, p = 0.002). CONCLUSIONS: Our analyses show serious nutritional
      deficiencies associated with higher grades of HRC and worse prognoses. Patients
      with haemorrhagic cystitis might benefit from an adequate dietary supplementation
      to support healing of their bladder mucosa.

PMID- 29460791
TI  - Hypercholesterolemia and hypertriglyceridemia as risk factors of liver
      dysfunction in children with inflammation receiving total parenteral nutrition.
AB  - BACKGROUND AND AIMS: Hepatic dysfunction, due to parenteral nutrition, may become
      severe and lead to cirrhosis and hepatic failure, especially in newborns and
      infants. This study aimed to evaluate the association between the exclusive use
      of total parenteral nutrition (TPN) and changes in the hepatic profile, and to
      investigate the relationship between age, hypertriglyceridemia, and
      hypercholesterolemia, and the occurrence of laboratory liver dysfunction.
      METHODS: A descriptive and historical cohort study was conducted, evaluating 195
      pediatric patients (age: 1 month to 19 years) who received TPN. The following
      hepatic and lipid profiles were assessed: alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl
      transferase (GGT), bilirubin, triglycerides (TGs), cholesterol, high-density
      lipoprotein (HDL), albumin, and transthyretin. High C-reactive protein and/or low
      HDL were considered indicative of inflammatory process. RESULTS: The majority of
      patients presented normal values of AST (79.2%), ALT (74.9%), GGT (56.4%), and
      alkaline phosphatase (68.1%). Total bilirubin changed in 68.5% of patients, and
      transthyretin and albumin were low in 87.3% and 65.1% of the patients,
      respectively. Incidences of high GGT values were related to age (odds ratio [OR],
      2.46; confidence interval [CI] 1.28-4.76; p = 0.007), hypercholesterolemia (OR,
      3.00; 95% CI, 1.24-7.25; p = 0.015), and hypertriglyceridemia (OR, 2.39; 95% CI,
      1.02-5.60; p = 0.046). Incidences of elevated ALT values were associated with
      hypercholesterolemia (OR, 4.57; 95% CI, 2.03-10.30; p < 0.001). CONCLUSION:
      Monitoring the hepatic profile from the early stage of TPN is necessary. Changes
      in the plasma lipid and hepatic profiles were frequently observed during the
      infusion of TPN, in patients with inflammation. Patients >2 years old and those
      with high TG and HDL levels were more likely to have elevated GGT levels.
      Hypercholesterolemia was associated with ALT alterations. Strategies to attenuate
      these issues should be considered in the early stages, in patients with TPN.

PMID- 29460792
TI  - Comparing assessment tools for detecting undernutrition in patients with liver
      cirrhosis.
AB  - BACKGROUND AND AIMS: Undernutrition in cirrhotic patients is often poorly
      recognised until late-stages. The current UK screening tool, the Malnutrition
      Universal Screening Tool, can miss undernutrition in patients with ascites/fluid
      retention. A 6-question Liver Disease Undernutrition Screening Tool (LDUST) has
      been developed in America. METHODS: We sought to compare LDUST with MUST in the
      detection of undernutrition in 50 inpatients and 50 outpatients with liver
      cirrhosis in a secondary care setting. This was then validated by a dietitian
      assessment. RESULTS: Similar patient demographics and liver disease aetiologies
      were found in the two cohorts. Mean Child-Pugh scores were higher for inpatients,
      8.3 (SD 1.9) vs 5.9 (SD 1.2). LDUST detected undernutrition in 45/50 inpatients
      (90%) and 34/50 outpatients (68%). MUST scores >=2 were present in 19/50 (38%)
      inpatients and 9/50 (18%) outpatients. In those with a MUST score <2, LDUST
      detected undernutrition in 26/31 (84%) inpatients and 27/41 (66%) outpatients. 26
      inpatients had undernutrition using LDUST but had a MUST score <2, 20 (76%) of
      these were deemed to be undernourished by dietetics assessment. LDUST was mostly
      completed independently or with minimal assistance (80% inpatients, 100%
      outpatients), with mean completion times of 4 and 3 min for in- and outpatients
      respectively. CONCLUSION: LDUST is a quick and easy screening tool, which appears
      better able than MUST to detect undernutrition in cirrhotic patients, including
      undernutrition missed by MUST. Importantly the tool was validated against
      dietitian assessments. The high rates of undernutrition among cirrhotic
      inpatients suggest that screening this cohort is unnecessary, and instead all
      should undergo dietitian review, with LDUST utilised in an outpatient setting.

PMID- 29460793
TI  - A prospective study of energy and protein intakes in critically ill patients.
AB  - BACKGROUND & AIMS: Providing adequate and appropriate food and nutrients
      satisfying the patients' safe nutritional need is one of the most important care
      practices for critically ill patients (CIPs) in ICU settings, and is strongly
      related to the patients' safety. METHODS: In this prospective cross-sectional
      study data were collected from a 52-bed medical intensive care unit on 777
      consecutive patients in six different ICUs. The patients' weights and heights
      were measured based on ulna length, knee height, MAC, Calf C, and Wrist C. Also,
      patient weight change history was asked for. All currently in-use dietary
      supplements and formulas in the ICU settings were checked for their ingredients.
      The patients' nutritional need was calculated individually for the disease state
      based on dietary ESPEN guidelines. RESULTS: Mean ICU and hospital stay duration
      was 14.45 +/- 11.81 and 15.38 +/- 11.88 days respectively. Mean energy and
      protein requirements in the target population were 1804.61 +/- 201.76 Kcal/day
      and 77.94 +/- 12.72 gr/day, respectively. Mean actual energy and protein intakes
      were 1052.75 +/- 561.25 Kcal/day and 35.38 +/- 23.19 gr/day, respectively.
      Satisfaction percents for mean energy and protein requirement in the total
      population were 58.34% (1052.75/1804.4) and 45.41% (35.38/77.9), respectively. In
      21.4% and 4.4% of the studied group, energy and protein intakes were about 75
      100% of the patients' actual need, respectively. Another data analysis for
      patients with over 10 days of inpatient time showed that only 14.2% of patients
      had energy intakes, and only 3.2% of them had protein intakes in the range of 75
      100% of their requirements. CONCLUSION: Results showed that energy and protein
      intakes in CIPs are low, disproportionate to their requirements. Therefore,
      actual dietary intake records, individual dietary requirement calculation, and
      individual dietary planning in relation with the patients' disease and stress
      should be considered. Such an accurate nutritional care process can promote
      patient safety.

PMID- 29460794
TI  - Definitions of hunger and fullness among youth enrolled in a pediatric weight
      management program.
AB  - The development and maintenance of obesity is multifactorial and involves the
      interplay of environmental, cultural, social, and biological influences. The
      purpose of the current paper was to describe hunger and fullness in a sample of
      pediatric patients seeking treatment for obesity. The goals of this study were to
      gain information about how youth with obesity describe their experience of being
      hungry and full and to explore common themes within these descriptions. Twenty
      five patients entering a Stage 3 pediatric obesity program responded to the open
      ended questions: "how do you know when you are hungry" and "how do you know when
      you are full?" The results found that the majority of youth used physical cues as
      a way to identify hunger and fullness cues. For identifying hunger, participants
      most frequently reported using cues such as their stomach growling or stomach
      pain as an indication that they are hungry. For identifying fullness, the
      majority of participants relied on discomfort. The current findings suggest that
      youth with obesity are able to attend to extreme physical cues (e.g., pain,
      sickness) of fullness but may not be aware of subtle cues that allow them to stop
      eating once they are satisfied.

PMID- 29460795
TI  - Evidence the U.S. autism epidemic initiated by acetaminophen (Tylenol) is
      aggravated by oral antibiotic amoxicillin/clavulanate (Augmentin) and now
      exponentially by herbicide glyphosate (Roundup).
AB  - Because certain hereditary diseases show autistic behavior, and autism often runs
      in families, researchers seek genes underlying the pathophysiology of autism,
      thus core behaviors. Other researchers argue environmental factors are decisive,
      citing compelling evidence of an autism epidemic in the United States beginning
      about 1980. Recognition that environmental factors influence gene expression led
      to synthesis of these views - an 'epigenetic epidemic' provoked by pervasive
      environmental agents altering expression of vulnerable genes, inducing
      characteristic autistic biochemistries in many mothers and infants. Two toxins
      most implicated in the U.S. autism epidemic are analgesic/antipyretic
      acetaminophen (Tylenol) and oral antibiotic amoxicillin/clavulanate (Augmentin).
      Recently herbicide glyphosate (Roundup) was exponentially implicated. What do
      these toxins have in common? Acetaminophen depletes sulfate and glutathione
      required to detoxify it. Oral antibiotics kill and glyphosate inhibits intestinal
      bacteria that synthesize methionine (precursor of sulfate and glutathione, and
      required to methylate DNA), bacteria that synthesize tryptophan (sole precursor
      of neuroinhibitor serotonin), and bacteria that restrain ammonia-generating
      anaerobes. Sulfate plus glutathione normally sulfate fetal adrenal androgen
      dehydroepiandrosterone to DHEAS - major precursor of placental/postnatal
      estrogens. Glyphosate (and heavy metals) also inhibit aromatase that turns
      androgens to estrogens. Placental/postnatal estrogens dehydrate/mature brain
      myelin sheaths, mature corpus callosum and left hemisphere preferentially, dilate
      brain blood vessels, and elevate brain serotonin and oxytocin. Stress-induced
      weak androgens and estrogen depletion coherently explain white matter asymmetry
      and dysconnection in autism, extreme male brain, low brain blood flow,
      hyperexcitability, social anxiety, and insufficient maternal oxytocin at birth to
      limit fetal brain chloride/water and mature GABA.

PMID- 29460796
TI  - Effects of goal-directed fluid therapy on enhanced postoperative recovery: An
      interventional comparative observational study with a historical control group on
      oesophagectomy combined with ERAS program.
AB  - BACKGROUND AND AIMS: The Enhanced Recovery after Surgery (ERAS) program has been
      proposed as a postoperative recovery-enhancing strategy. We frequently apply the
      Modified-ERAS program following oesophagectomy. This study aims to elucidate the
      impact of goal-directed fluid therapy (GDT) for the perioperative management of
      oesophageal cancer on the postoperative recovery of patients undergoing
      oesophagectomy. METHODS: This is an interventional before-after comparative
      observational study conducted at Kanagawa Cancer Centre, Japan. Patients who
      underwent elective oesophagectomy for oesophageal cancer were recruited. Group H
      (retrospectively collected) received intraoperative and postoperative management
      consisting of fluid administration without haemodynamic monitoring and the M-ERAS
      program, while Group S prospectively received management consisting of GDT and
      the M-ERAS program. The primary endpoint was the speed of gastrointestinal
      functional recovery, while secondary endpoints were the level of postoperative
      mobilisation, incidence of complications, postoperative length of hospital stay
      (LOS), and nutritional status after discharge. RESULTS: The proportion of
      patients who completely egested Gastrografin by postoperative day 4, the level of
      postoperative mobilisation, and achievement ratio for a 100-m walk on the first
      postoperative attempt were significantly higher in Group S than in Group H (P =
      0.034, P = 0.0197, and P < 0.0001, respectively). No significant differences were
      observed in the postoperative LOS and incidence of complications within 30 days
      between the groups. The serum albumin levels at 6 months after discharge was
      higher in Group S than in Group H (P = 0.0002). CONCLUSIONS: The GDT-ERAS program
      enhanced postoperative gastrointestinal recovery and mobilisation, as well as
      postoperative nutritional status and protein synthesis. The program did not
      affect either postoperative LOS or the incidence of complications. TRIAL
      REGISTRATION: UMIN registration number: UMIN000013705,
      https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000015999.

PMID- 29460797
TI  - Insights of hypercarotenaemia: A brief review.
AB  - Carotenoids are generally 40-carbon tetraterpenoids responsible for most of the
      yellow, orange and red colours throughout the natural world. Pro-vitamin A
      carotenoids serve as the precursors of vitamin A. In addition to that,
      carotenoids exhibit range of important protective mechanisms in human health.
      Hypercarotenaemia is characterized by carotenodermia resulting in yellowing of
      the skin specially palms and soles. Hypercarotenaemia develops in subjects
      consuming high levels of carotenoid rich foods or beta-carotene supplements (>30
      mg day-1) over a period of months. Less or normal intake of carotenoids very
      rarely gives rise to metabolic carotenaemia due to genetic defects of the enzyme
      15-15'-carotenoid dioxygenase. Moreover, it is known that those with
      hypothyroidism and diabetes mellitus tend to develop hypercarotenaemia with the
      normal intake of carotenoid rich foods. Further, hypercarotenaemia has been
      reported in anorexia nervosa. However, recently some studies have been shown that
      there is no major correlation between carotenoid intake and hypercarotenaemia
      indicating that a genetic factor is at play in development of hypercarotenaemia.
      Therefore, the subjects appear to need to be genetically pre-disposed to
      hypercarotenaemia.

PMID- 29460798
TI  - Major liver resection reduces nonprotein respiratory quotient and increases
      nonesterified fatty acid at postoperative day 14 in patients with hepatocellular
      carcinoma.
AB  - BACKGROUND & AIMS: We reported decreased nonprotein respiratory quotient (npRQ)
      after liver resection in patients with hepatocellular carcinoma (HCC); however,
      whether liver resection volume affects energy metabolism in these patients is
      unclear. We aimed to examine the relationship between liver resection and energy
      metabolism indices. METHODS: NpRQ was measured in 53 patients with HCC and seven
      with at the pre- and postoperative days. Patients were classified into four
      groups: Minor-lowICG group (n = 17): minor (subsegment or less) resection and low
      indocyanine green retention rate at 15 min (ICGR15) (<15%); Minor-highICG group
      (n = 18): minor resection and high ICGR15 (>=15%) and Major-lowICG group (n =
      18): major (lobe) resection and low ICGR15 (<15%). We investigated dietary intake
      and blood biochemistry at energy measurement. The difference in npRQ and
      nonesterified fatty acid (NEFA) pre- and post-hepatectomy was shown as DeltanpRQ
      and DeltaNEFA, respectively. RESULTS: Compared with the preoperative values, npRQ
      significantly decreased in the Minor-highICG and Major-lowICG groups and NEFA
      significantly increased in the Major-lowICG group at postoperative day 14. In
      single regression analysis, DeltanpRQ significantly correlated with HCV infection
      and DeltaNEFA with resection volume, HCV infection, and ICGR15. In multiple
      regression analysis, DeltaNEFA significantly correlated with resection volume
      after adjusting for age, etiology, and ICGR15. CONCLUSIONS: These results suggest
      that postoperative nutritional recovery is slower in major resection than in
      minor resection patients. Hence, nutritional care to prevent starvation is needed
      in major resection patients.

PMID- 29460799
TI  - Customized nutrition intervention and personalized counseling helps achieve
      nutrition targets in perioperative liver transplant patients.
AB  - BACKGROUND AND AIM: Nutritional therapy is an integral part of care in all phases
      of liver transplantation (LTx). However, there are several factors that make it a
      challenge to manage malnutrition in these patients including, but not limited to,
      loss of appetite, dietary restrictions and dietary habits. Dietary habits are
      guided by personal choice, social, cultural and regional background with
      diversity ranging from veganism to vegetarianism with the latter predominant in
      Indian population. Therefore, it is difficult to improve nutritional intake of
      patients with standard dietary recommendations. We evaluated the effects of
      implementing personalized dietary counseling and a customized nutrition plan on
      its ability to enhance oral intake and, thereby improve nutritional status of
      patients with end stage liver disease (ESLD) being evaluated for LTx. We compared
      the outcomes with a matched group of patients who were prescribed standard
      dietary recommendations from a historic database. Primary outcome was measured by
      number of patients achieving >=75% of recommended energy and protein requirements
      during hospitalization for LTx. Secondary outcomes included mean energy and
      protein intake, hours of ventilation, length of stay in Intensive Care Unit (ICU)
      and hospital, mortality and readmission rate in the acute phase (3months) after
      LTx. METHODS: This was a prospective observational study, performed at a single
      LTx centre. All patients >18years who enrolled for LTx and consented for the
      study were included. The study was conducted after obtaining institutional ethics
      committee approval. A protocol based nutrition planning was implemented from
      April'14. According to this protocol, all patients being evaluated for LTx
      underwent a detailed nutritional assessment by a qualified Clinical Dietitian
      (CD) and regularly followed up with until LTx. Nutritional intervention,
      including a customized nutrition care plan and personalized dietary counseling,
      was provided based on the severity of malnutrition. To evaluate the efficacy of
      this protocol, we compared the nutritional adequacy (calorie and protein intake)
      of 65 consecutive patients who underwent LTx between August'14-October'15 (group
      1) with a historic database of 65 patients who underwent LTx between January'13
      and April'14 (group 2). Patients' demographics, disease severity score, baseline
      markers of nutritional status (subjective global assessment (SGA), and body mass
      index (BMI)), were recorded. First, assessment of individual patient's oral
      energy and protein intake was determined by the daily calorie count during
      hospitalization. Then the nutritional intervention (oral nutrition supplement
      (ONS)/enteral nutrition (EN)/parenteral nutrition (PN)) plan was customized
      according to their spontaneous oral intake. As part of the protocol, health
      related quality of life was also assessed using short form 8 (SF-8) in group 1.
      Statistical analyses using Pearson's correlation, Chi-Square test were applied
      with SPSS version 20.0. RESULTS: The mean age of group 1 and 2 were 52.6 +/- 9.8,
      51.9 +/- 10.5 (range 25-70years) with BMI of 26.8 +/- 6.0, 26.5 +/- 5.4
      respectively. According to SGA, there was significant improvement in the
      nutritional status of group 1 patients compared to group 2 on admission for LTx.
      It was indicated that 88% of group 1 individuals in comparison to 98% in group 2
      were malnourished. The calorie intake of group 1 (1740.2 +/- 254.8) was
      significantly higher than group 2 (1568.5 +/- 321.6) (p = 0.005). The marked
      improvement in protein intake in group 1 (63.1 +/- 12.1) when compared with group
      2 (53.1 +/- 13.4) was statistically significant (p = 0.008). A subset analysis
      showed that non-vegetarians (consuming meat and dairy products) between the
      groups showed that group 1 had a significantly higher calorie (p = 0.004) and
      protein (p = 0.0001) intake compared to individuals in group 2. Following
      implementation of study's protocol, the goal of achieving >=75% of the prescribed
      calories (p = 0.013) and protein (p = 0.0001) was significantly higher in group
      1. CONCLUSION: When compared to the standard prescription, an individualized
      protocol to diagnose, stratify the severity of malnutrition early, and follow up
      by customized nutrition planning for patients helped to achieve nutritional
      targets more effectively. Inspite of patients' diversity in nutritional habits
      and reluctance to accept change, it is clear that a qualified and dedicated
      transplant nutrition team can successfully implement perioperative nutrition
      protocol to achieve better nutritional targets.

PMID- 29460800
TI  - Diet and cardiometabolic side effects in children treated with second-generation
      antipsychotics.
AB  - BACKGROUND: Second-generation antipsychotic (SGA) treatment in children is
      associated with metabolic side effects including weight gain, dyslipidemia, and
      insulin resistance. The objective of this study is to determine if SGA treatment
      in children affects dietary intakes and relationship to metabolic side effects.
      METHODS: Three-day food records assessed dietary energy and macronutrient intakes
      in a cross-sectional population of SGA-treated (n = 35) and SGA-naive (n = 29)
      children. RESULTS: SGA-treated children had more overweight/obesity (BMI >= 85th
      percentile for age and sex, p = 0.001); waist circumference (WC) >= 90th
      percentile for age and sex (p = 0.007); waist:height ratio (WHtR) >= 85th
      percentile for age and sex (p = 0.004), greater HOMA-IR, (p = 0.001) and plasma
      triglycerides (p = 0.017), and lower plasma HDL (p = 0.029). Dietary energy
      intakes were not different between SGA-naive and SGA-treated children [1734 +/-
      486 vs 1971 +/- 649 (-135, 408) kcal/day, mean +/- SD (95% CI)] after adjustments
      for sex, age, Tanner stage, psychostimulant use, and height. Similarly, no
      differences in macronutrient intakes were observed. In models adjusted for SGA
      treatment and physical activity, no relationships between dietary intakes and BMI
      were found, but dietary total energy intakes were positively associated with
      waist circumference z-scores (p = 0.019), systolic blood pressure z-scores (p =
      0.028, also adjusted for BMI) and HOMA-IR (p = 0.013, also adjusted for age, sex,
      BMI). All of the children had poor diets with 87.5% having >7% of daily energy
      from saturated fat; 62.5% having >20% of daily energy from sugar; and almost 60%
      having sodium intakes above the tolerable upper intake level. CONCLUSIONS: SGA
      treatment is not associated with greater dietary energy intakes in children.
      However, dietary energy intakes are associated with greater waist circumference
      and systolic blood pressure z-scores and HOMA-IR in children with mental health
      conditions.

PMID- 29460801
TI  - Effects of glucocorticoids on serum amino acid levels during cardiac surgery in
      children.
AB  - BACKGROUND AND AIMS: Children undergoing cardiac surgery with cardio pulmonary
      bypass often receive glucocorticoids to reduce the systemic inflammatory
      response. Glucocorticoids stimulate protein breakdown and increase amino acid
      availability. We studied whether glucocorticoid treatment influences the
      availability of amino acids, specifically those involved in the nitric oxide
      pathway. METHODS: We prospectively studied 49 children with congenital heart
      disease undergoing cardiac surgery. Serum cortisol and amino acid levels were
      measured in arterial blood sampled before surgery (t = -5 min), directly after
      surgery (t = 0 h) and at t = 12 h and t = 24 h after surgery. Serum cortisol and
      amino acid levels were compared between children who had received glucocorticoids
      (G+) and children who had not (G-). RESULTS: Of 49 patients included ((49% male,
      age 1.7 (0.5-8.7) y)), 33 (67%) received glucocorticoids. Baseline
      characteristics were not different between groups, except a higher weighted
      inotropic score in the G+ group. At t = 0 h, serum cortisol levels in the G+
      group were significantly higher than in the G- group (7218 vs. 660 nmol/L; (p <
      0.05)), but not different at the other time points. The levels of plasma amino
      acids had dropped after surgery. Compared to the G- group, in the G+ group the
      total amount of amino acids was significantly higher at t = 12 and t = 24;
      citrulline levels were higher at t = 12 and t = 24; and glutamine and arginine
      levels were higher at t = 12. CONCLUSIONS: Glucocorticoid treatment during
      cardiac surgery in children preserves serum amino acid levels post-surgery. The
      preservation of glutamine, citrulline and arginine levels might have a beneficial
      effect on the related NO metabolism.

PMID- 29460802
TI  - Can Quantab titrator sticks reliably predict urinary sodium?
AB  - BACKGROUND & AIMS: Urinary sodium concentration is a commonly used marker for
      extracellular fluid depletion which is often associated with dehydration. A point
      of care test for urinary sodium may reduce delays in clinical decision making by
      offering more timely guidance leading to improved salt and fluid management. We
      compared laboratory assessed urinary sodium with a potential point of care
      measure of urinary chloride in a variety of in- and outpatient specialities, to
      explore its use as an indicator of low urine sodium. METHODS: Urinary chloride
      concentrations were estimated using a Quantab titrator stick in samples from
      patients that had been sent for urinary sodium assays. We validated the results
      of this titrator stick with laboratory-assessed sodium concentrations by deriving
      correlation coefficients between these methods and using limits of agreement
      testing. We determined the optimal titrator stick cut-point for identifying low
      urinary sodium (urinary sodium <20 mmol/L) by maximising the product of the
      sensitivity and specificity. This level of urinary sodium was used to mirror the
      British Society of Gastroenterology guidance on short bowel patients Nightingale
      and Woodward, 2006. RESULTS: We obtained laboratory urinary sodium concentration
      and Quantab stick chloride measures on 127 samples. Twenty three percent had a
      urinary sodium below 20 mmol/L so were regarded as biochemically dehydrated. A
      threshold of <4.3 on the Quantab scale had a positive predictive value for low
      sodium of 56% (95%CI 40%-71%) and a negative predictive value of 94% (95%CI 87%
      98%). CONCLUSIONS: These data suggest that the Quantab stick could be used as a
      point of care test to aid fluid and salt management decisions in an outpatient
      setting. Further work to explore the use of the titrator stick in specific
      patient populations at risk of salt and water depletion is justified.

PMID- 29460803
TI  - Vitamin D status in children with headache: A case-control study.
AB  - BACKGROUND: Vitamin D is a fat soluble vitamin with hormonal properties, plays
      crucial functions in bone and mineral metabolism and has important regulatory
      functions in brain development, cell differentiation and apoptosis. Some studies
      have shown a link between vitamin D deficiency and headache. MATERIAL AND
      METHODS: In this study, 147 patients with headache (migraine or either tension
      type headache (TTH)) and 69 healthy controls, aged 5 to 16 years, were evaluated.
      Each group was also divided into two separate sub-groups based on presentation to
      the clinic in either high solar-exposure (HSE) and low solar-exposure (LSE).We
      retrospectively evaluated the levels of calcium, phosphorus, alkaline
      phosphatase, parathyroid hormone, and 25-OH vitamin-D3. Levels below 20 ng/ml
      were described as vitamin D deficiency and levels of 2030 ng/ml as vitamin D
      insufficiency. RESULTS: The levels of 25-OH vitamin-D3 were statistically
      significantly lower when compared to the control group (17.1+/-9.4 vs. 25.8 +/-
      12.8 ng/mL, respectively; p < 0.001). This held true for both the HSE and LSE
      group compared to the control group (for the group 1; 24.6 +/- 11.8 vs. 32.1 +/-
      10.6 ng/mL, respectively; p = 0.007, and for the group 2; 14.5 +/- 6.8 vs. 19.6
      +/- 13.5 ng/mL, respectively; p = 0.003). Also in headache subgroups (migraine
      and TTH), vitamin D levels were significantly lower than the control group (17.3
      +/- 9.0, 16.9 +/- 9.9 and 25.8 +/- 12.8 ng/mL respectively; p < 0.001).
      CONCLUSION: There may be a relationship between vitamin D deficiency and
      headache, with particular significance in LSE. We suggest that this conclusion
      needs to be supported with randomised clinical studies containing a larger
      numbers of samples and controls.

PMID- 29460804
TI  - The costs of disease related malnutrition in hospitalized children.
AB  - INTRODUCTION: Disease related malnutrition (DRM) is a serious medical condition
      which is associated with an increase in morbidity and mortality, augmenting
      resource use and associated costs. DRM can be detected by actively and fully
      assessing the nutritional status. Studies in adult malnourished patients have
      shown that the additional health care costs are about ? 2 billion (? 2000
      million) per year. The objective of the current study was to estimate the annual
      additional costs of DRM for pediatric patients as was done for adults. METHODS: A
      cost-of-illness analysis was performed to calculate the annual additional costs
      of DRM in 2015 pediatric patients (aged 1 month up to and including 17 years)
      admitted to non-academic hospitals in The Netherlands. DRM was assessed with
      weight-for-age, weight-for-height and height-for-age. Input variables in the
      formula used were length of stay and prevalence of DRM. The costs were estimated
      per disease as classified in the International Classification of Diseases by the
      WHO (ICD-10), per gender and age group. The results were expressed as an absolute
      monetary value as well as a percentage of the Dutch national health expenditure.
      Robustness of the results was checked by a sensitivity analysis. RESULTS: The
      total additional direct medical costs of DRM in pediatric patients in 2013 were
      estimated to be ? 51 million for acute malnutrition, ? 46 million when focused on
      chronic malnutrition and ? 80 million in case of overall malnourished children.
      This equals 5.6% of the total Dutch hospital costs for these hospitalized
      children. CONCLUSIONS: This study has shown that DRM in hospitalized children is
      associated with an increase in annual hospital costs with an additional amount of
      ? 80 million, of which acute malnutrition account for the largest part.

PMID- 29460805
TI  - Incidence of metabolic bone disease in preterm infants of birth weight <1250 g
      and in those suffering from bronchopulmonary dysplasia.
AB  - BACKGROUND & AIMS: Preterm infants are exposed to a higher risk of developing
      Metabolic Bone Disease (MBD) with an increased bone fragility, a higher fracture
      risk and a long-term reduced linear growth and childhood height. Monitoring bone
      growth has become mandatory in neonatology. Several risk factors have been
      identified among the population of extremely low birth weight infants, but we
      still do not know which is the real incidence of MBD since its evaluation is not
      routinely performed worldwide. The aim of this study was to evaluate the
      incidence of MBD in preterm infants and in those suffering from bronchopulmonary
      dysplasia (BPD). METHODS: Prospective evaluation of patients who developed BPD
      (BPD group) versus infants who did not develop it (no-BPD group). We examined, in
      preterms <1.250 g, the metacarpus bone transmission time (mc-BTT) at birth, 21
      days and 36 weeks of gestational age (GA) together with biochemical markers of
      bone status. RESULTS: We included 135 patients, 55 with BPD. BPD patients
      received less total proteins in the first two weeks and less energy in the first
      month of life (p = 0.007 and p < 0.001 respectively). BPD patients had a worse
      growth velocity at two weeks of age (12.36 +/- 7.86 vs 16.59 +/- 7.05 g/kg/day, p
      = 0.001). At 21 days, BPD patients had lower phosphatemia (1.65 +/- 0.031 mmol/L
      vs 1.85 +/- 0.034 mmol/L, p = 0.007) and higher alkaline phosphatase levels
      (411.62 +/- 135.31 IU/l vs 338.98 +/- 102.20 IU/l, p = 0.005). BPD patients had
      significantly worse mc-BTT at 36 weeks GA (0.45 +/- 0.06 vs 0.50 +/- 0.08 MUsec,
      p < 0.001) and a higher incidence of MBD (60% vs 34%; p = 0.012). CONCLUSIONS:
      BPD infants are a special subset of patients among preterms who receive, in the
      first month of life, a lower energy intake than patients without BPD. BPD
      patients have a suboptimal bone growth and a higher incidence of MBD. Monitoring
      growth, bone status and optimizing nutritional intakes need to be further
      improved in preterm infants with BPD.

PMID- 29460806
TI  - Vitamin D deficiency and associated factors among pregnant women of a sunny city
      in Northeast of Brazil.
AB  - OBJECTIVE: We analyzed the serum vitamin D concentrations and identified the
      factors associated with vitamin D deficiency in Brazilian pregnant women, in a
      city with a high solar exposure. METHODS: Cross-sectional study with a sample of
      190 pregnant women in a municipality in the Brazilian state of Bahia. Socio
      environmental information, regarding the lifestyle and biological factors of
      participants, was collected and recorded in a questionnaire, and serum
      concentrations of 25(OH)D was determined (PR). RESULTS: The deficient and
      insufficient vitamin D concentrations were found in 14.21% and 44.74% of the
      pregnant women, respectively. Vitamin D deficiency was associated with commuting
      to work via motor vehicles (PR: 2.79; 95% CI: 1.06-7.31), with winter (prevalence
      ratio - PR: 1.54; 95% CI: 1.01-2.35), exposure to the sun only on the face and
      hands (PR: 2.99; 95% CI: 1.35-6.63) and single pregnant women (PR: 2.53; 95% CI:
      1.01-6.35). CONCLUSIONS: We detected a high proportion of pregnant women with
      vitamin deficient and insufficient vitamin D levels among pregnant women of a
      sunny city. These data suggest the necessity to monitor serum vitamin D levels
      during pregnancy and the adequate orientation in prenatal care to adoption
      healthy lifestyle for the prevention of vitamin D deficiency in this population.

PMID- 29460807
TI  - Improved nutrition for extremely preterm infants - A population based
      observational study.
AB  - BACKGROUND AND AIMS: Extremely preterm (EPT) infants are at high risk for
      malnutrition due to immaturity and medical complications and they often
      accumulate nutritional deficits and experience growth faltering during treatment
      at neonatal intensive care units (NICUs). Enhanced intake of energy and protein
      during the first weeks of life improves weight gain and head circumference
      growth. The optimal nutritional strategy for these infants' health and long-term
      development remains unknown. Nutritional regiments have been identified as a
      potential area for improvement in Swedish NICUs. The aim of this study was to
      evaluate changes in nutritional intake over time during the first 56 postnatal
      days in EPT (<27 gestational weeks; n = 316) infants, who were treated in NICUs
      during 2004-2011 in Stockholm, using a population-based study approach. METHODS:
      Several different nutritional interventions were implemented over the 8-year
      period. Nutrition and growth data were obtained retrospectively from hospital
      records. All intakes of enteral and parenteral nutrients were retrieved daily
      during the first 28 postnatal days and on days 35, 42, 49 and 56. RESULTS: Energy
      intake (median) increased from 77 kcal/kg/d during the 2004-2005 period to 98
      kcal/kg/d during the 2010-2011 period on days 4-6. Median protein intake
      increased from 2.4 g/kg/d during 2004-2005 to 3.6 g/kg/d during 2010-2011. Energy
      and protein intake during postnatal days 0-6 increased continuously over the 8
      years and protein intake increased during all 56 postnatal days. Full enteral
      feeds were reached earlier and the proportion of enteral feeds during the first
      week was higher during 2008-2009 compared to all other years. A significant
      improvement in growth was primarily noted by comparing the 2004-2005 period to
      subsequent years. CONCLUSIONS: Neonatal nutrition improved significantly in
      Stockholm from 2004 to 2011. Above all, parenteral nutrition was initiated more
      promptly during the first week and was provided at higher quantities. However,
      many of the EPT infants born during the later years still did not reach the
      recommended macronutrient intake levels. A significant weight gain improvement
      was observed between 2004-2005 and 2006-2011.

PMID- 29460808
TI  - Dietary poultry intake and the risk of stroke: A dose-response meta-analysis of
      prospective cohort studies.
AB  - BACKGROUND & AIMS: We performed a meta-analysis to illuminate and quantify the
      potential relationship between poultry intake and risk of stroke through
      summarizing available evidence using a dose-response meta-analysis of prospective
      cohort studies. METHODS: Pertinent prospective cohort studies attained using
      electronic searches through PubMed, and Scopus up to September 25th, 2017.
      Relative risks (RR) s with corresponding 95% confidence intervals (CIs) of the
      highest versus the lowest for cohort studies were evaluated using DerSimonian and
      Laird random-effects models to find combined RRs. We also assessed the dose
      response effect of this relationship. RESULTS: A total of 7 studies involving 354
      718 participants were met inclusion criteria. The pooled RR of total stroke risk
      was [RR = 0.92 95% CI, 0.82, 1.03, I2 = 19.8%, Pheterogeneity = 0.28] for the
      highest versus lowest categories of poultry intake. Subgroup analysis showed an
      inverse associations for the US people [RR = 0.86 95% CI, 0.77, 0.95, I2 = 0.0%,
      Pheterogeneity = 0.38] and women [RR = 0.83, 95% CI, 0.72, 0.93, I2 = 0.0%,
      Pheterogeneity = 0.63]. We did not obtain any significant association in the
      subtypes of strokes with highest versus lowest poultry intake [Ischemic stroke
      (RR = 0.91; 95% CI: 0.79, 1.02, I2 = 0.0%, p = 0.93), Hemorrhagic (RR = 0.82; 95%
      CI: 0.59, 1.04, I2 = 20.5%, Pheterogeneity = 0.28)]. One serving per week
      increment in poultry intake was not associated with the risk of stroke (RR: 1.00,
      95% CI: 0.96, 1.03, I2 = 69.0%, Pheterogeneity = 0.004). Nonlinear dose-response
      meta-analysis showed lower risk of stroke at consumption ~1 serving/week.
      CONCLUSION: Our meta-analysis revealed that poultry intake is not associated with
      total stroke risk; furthermore, an inverse relationship in US population and
      females must be interpreted with caution.

PMID- 29460809
TI  - Cut-off points for weight gain during pregnancy: Risk of gestational diabetes.

PMID- 29460810
TI  - Consequences of an extreme diet in the professional sport: Refeeding syndrome to
      a bodybuilder.
AB  - Refeeding syndrome, as a life-threatening condition, is well known among severely
      malnourished or deeply metabolically stressed patients. This case presents an
      atypical manifestation of the syndrome to a young bodybuilder, whose extreme
      diet, including 5 months of insufficient nourishment before the sport competition
      and 6 days of carbohydrates overload afterwards, has led him to a bilateral lower
      - limb paralysis and drastic homeostatic disturbances. Severe hypokalemia,
      hypophosphatemia, hypomagnesemia and hyperglycemia with mildly elevated liver
      enzymes have occurred. The patient could barely move his legs and arms, and his
      state has been followed by a hypertensive crisis, which required an immediate
      intravenous treatment. Although his weight was 112,5 kg with a body mass index of
      32,2 kg per square meter, and his blood serum albumin concentration resulted
      inside the normal range, the overall condition was corresponding to the state of
      extenuated and malnourished patients. This case reflects to high prevalence of
      eating disorders or non-adequate nutrition among weight-sensitive sport athletes.
      The importance of prevention and opportune diagnostics of refeeding syndrome
      among special vulnerable groups should be considered.

PMID- 29460811
TI  - Effects of a novel method for enteral nutrition infusion involving a viscosity
      regulating pectin solution: A multicenter randomized controlled trial.
AB  - BACKGROUND & AIMS: The initial complications associated with infusion of enteral
      nutrition (EN) for clinical and nutritional care are vomiting, aspiration
      pneumonia, and diarrhea. There are many recommendations to prevent these
      complications. A novel method involving a viscosity-regulating pectin solution
      has been demonstrated. In Japan, this method along with the other so-called "semi
      solid EN" approaches has been widely used in practice. However, there has been no
      randomized clinical trial to prove the efficiency and safety of a viscosity
      regulating pectin solution in EN management. Therefore, we planned and initiated
      a multicenter randomized controlled trial to determine the efficiency and safety.
      METHODS: This study included 34 patients from 7 medical institutions who
      participated. Institutional review board (IRB) approval was obtained from all
      participating institutions. Patients who required EN management were enrolled and
      randomly assigned to the viscosity regulation of enteral feeding (VREF) group and
      control group. The VREF group (n = 15) was managed with the addition of a
      viscosity-regulating pectin solution. The control group (n = 12) was managed with
      conventional EN administration, usually in a gradual step-up method. Daily
      clinical symptoms of pneumonia, fever, vomiting, and diarrhea; defecation
      frequency; and stool form were observed in the 2 week trial period. The dose of
      EN and duration of infusion were also examined. RESULTS: A favorable trend for
      clinical symptoms was noticed in the VREF group. No significant differences were
      observed in episodes of pneumonia, fever, vomiting, and diarrhea between the 2
      groups. An apparent reduction in infusion duration and hardening of stool form
      were noted in the VREF group. CONCLUSIONS: The novel method involving a viscosity
      regulating pectin solution with EN administration can be clinically performed
      safely and efficiently, similar to the conventional method. Moreover, there were
      benefits, such as improvement in stool form, a short time for EN infusion, and a
      reduction in vomiting episodes, with the use of the novel method. This indicates
      some potential advantages in the quality of life among patients receiving this
      novel method.

PMID- 29460812
TI  - The acute effect of black tea consumption on resistance artery endothelial
      function in healthy subjects. A randomized controlled trial.
AB  - BACKGROUND & AIMS: Black tea is a main source of flavonoids in the Western diet
      and has been associated with reduced risk for cardiovascular disease, possibly
      through lowering blood pressure. These effects may be mediated through improving
      endothelial function of resistance arteries. The aim of this study was therefore
      to examine the acute impact of black tea on forearm resistance artery endothelial
      function in healthy, normotensive middle-aged subjects. METHODS: Twenty middle
      aged men and women (age-range 45-75 years) were recruited into a double-blind,
      randomized, placebo-controlled crossover intervention study. Forearm resistance
      artery blood flow (FBF, measured using venous occlusion plethysmography) in
      response to incremental doses of acetylcholine, sodium nitroprusside and L-NG
      monomethyl arginine were determined 2 h after consumption of either black tea
      containing ~400 mg flavonoids (equivalent to 2-3 cups of tea) or a taste- and
      color-matched placebo. RESULTS: The mean FBF-response to acetylcholine after tea
      consumption was 23% higher compared to the response after placebo (95% CI: -20%,
      +88%), but this difference did not reach statistical significance (P = 0.32). No
      significant differences in the FBF-responses to sodium nitroprusside and L-NG
      monomethyl arginine were found between the tea and placebo interventions (P =
      0.96 and 0.74, respectively). Correcting FBF for changes in blood pressure did
      not alter the outcomes. CONCLUSIONS: We found no evidence that acute intake of
      black tea significantly altered endothelium-dependent vasodilation of forearm
      resistance arteries in healthy middle-aged subjects. Interventions with a longer
      duration of tea ingestion are required to further explore the (long-term) impact
      of tea flavonoids on blood pressure regulatory mechanisms. This trial was
      registered at clinicaltrials.gov as NCT02328339.

PMID- 29460813
TI  - Surplus vitamin B12 use does not reduce fatigue in patients with Irritable Bowel
      Syndrome or inflammatory bowel disease: A randomized double-blind placebo
      controlled trial.
AB  - OBJECTIVE: In non-conventional care, high doses of vitamin B12 supplementation
      are used for the treatment of fatigue even in case of normal vitamin B12 blood
      levels. We performed a randomized placebo controlled trial to investigate the
      effect of surplus oral vitamin B12 supplementation on fatigue in patients with
      IBS or IBD. METHODS: This randomized double-blind, placebo-controlled trial
      included 95 out-clinic IBS and IBD patients with deactivating fatigue and normal
      vitamin B12 blood levels (>=150 pmol/l) aged 18-65 years. Participants were
      randomly assigned to receive 1000 MUg vitamin B12 daily or a placebo supplement
      for 8 weeks. The primary outcome measure was fatigue (Checklist Individual
      Strength (CIS)). In addition, measures of quality of life and depression were
      examined. RESULTS: No significant difference in scores of the CIS subscale
      'subjective fatigue' was observed between the intervention group and the control
      group with changes in scores of -8.1 +/- 9.5 and -8.3 +/- 10.6 (95% CI -11.65 to
      6.71), respectively. The scores on the CIS subscale 'motivation' improved with a
      significant change in scores of -2.2 +/- 4.6 (95% CI -4.4 to -0.04). No
      significantly increased scores were observed for depression or quality of life in
      the intervention group compared to the control group. CONCLUSION: This study did
      not confirm the expected effect of non-conventional surplus vit B12
      supplementation on fatigue in IBS or IBD patients. In addition, no positive
      effect was observed on depression or quality of life. We conclude that surplus
      treatment with vitamin B12 in IBS and IBD patients suffering from fatigue has no
      beneficial clinical effect.

PMID- 29460814
TI  - Smoking cessation contributes to weight gain in patients with
      hepatobiliopancreatic malignancy.
AB  - BACKGROUND & AIMS: The relationship between smoking cessation and weight gain is
      well recognized. However, there is no data currently available on the effect of
      smoking cessation on weight gain in patients with malignancy. The aim of this
      study was to clarify the body weight (BW) change after smoking cessation in
      patients with malignancy. METHODS: We retrospectively analyzed 159 subjects who
      underwent hepatobiliopancreatic surgery. The smoking status was determined using
      questionnaires administered at the initial presentation, and the candidates were
      divided into two groups: recent quitters and nonsmokers. The change in the BW was
      compared between these two groups. RESULTS: There were 134 subjects with
      malignant disease (84.3%), with a median age of 68 (range: 26-84) years. In the
      nonsmoker group, 28 of 116 subjects (24.1%) gained weight between the initial
      presentation and admission. In the recent quitter group, 12 of 18 subjects
      (66.7%) gained weight in the same period (P < 0.01). Regarding the change in the
      BW from the initial presentation, recent quitters gained more weight than
      nonsmokers (+1.7 kg [+2.7%] vs. -1.0 kg [-2.0%], P < 0.01). Furthermore, the
      improvement from the initial presentation was seen in a higher percentage of
      recent quitters than nonsmokers with respect to Onodera's prognostic nutritional
      index (61.1% vs. 36.2%, P = 0.04) and the controlling nutritional status score
      (38.9% vs. 19.3%, P = 0.07). CONCLUSIONS: Weight gain due to smoking cessation
      was observed even in patients with hepatobiliopancreatic malignancy.

PMID- 29460815
TI  - Phase angle is related to outcome after ICU admission; an observational study.
AB  - INTRODUCTION: Malnutrition at the time of ICU admission is associated with an
      increased morbidity and mortality. Malnutrition is most often assessed by a
      questionnaire but can also be determined with bio-impedance and measurement of
      phase angle. In a single-centre observational study we compared the percentage of
      malnutrition in patients admitted to our ICU, according to the Short Nutritional
      Assessment Questionnaire (SNAQ) with the phase angle measured with bio-impedance.
      Furthermore, we questioned whether malnutrition is related to outcome parameters.
      METHODS: In a 15 week period consecutive patients admitted to the ICU were
      included. Exclusion criteria included age <18 years, anatomical and/or
      neurological abnormalities of the limbs and an ICU stay less than 6 h. Bio
      impedance measurements were performed shortly after admission, the SNAQ was
      obtained from the patient or legal representative. Malnutrition is considered
      with a SNAQ >=2 or a phase angle of <5 degrees  for men and <4.6 degrees  for
      women. The study was approved by our local ethical committee (MCL, nWMO 77, April
      18, 2015). RESULTS: 299 Patients were included (66% male, age 66 +/- 12 year, BMI
      27 +/- 4 kg/m2 and APACHE II score 14 [11-17]), of which 64% elective and 36%
      acute admissions. Hospital mortality was 7.4%. Malnutrition was present in 16%
      according to the SNAQ and in 36% according to phase angle. There was a fair
      accordance between the SNAQ and phase angle. Phase angle was significantly higher
      in patients with a SNAQ score of 0-1 (5.5 degrees +/-1.3) in comparison with
      patients with a SNAQ score >=2 (4.4 degrees +/- 1.1) (p < 0.001). Logistic
      regression analysis showed a significant relation between SNAQ and BMI, malignant
      disease and hospital length of stay and between phase angle and age, sex, BMI,
      malignant disease, hospital length of stay and hospital mortality. CONCLUSION:
      Malnutrition was present in 16% according to the SNAQ and in 36% according to
      phase angle in our IC population. Malnutrition was associated with prolonged
      hospital length of stay. In this small population of mixed ICU patients, a low
      phase angle was found to independently predict hospital mortality. CLINICAL
      TRIALS. GOV NUMBER: NCT02911181.

PMID- 29460816
TI  - Chilli intake is inversely associated with hypertension among adults.
AB  - BACKGROUND & AIMS: This study aimed to examine the association between chilli
      intake and the incidence of hypertension in a Chinese adult population. METHODS:
      Adults aged 20-75 years in the China Health and Nutrition Survey were followed
      from 1991 to 2011. Dietary data were collected during home visits using a 3-day
      food record in 1991, 1993, 1997, 2000, 2004, 2006, 2009 and 2011. Cox regression
      was used in the analysis. Blood pressure was measured at each data collection
      point. RESULTS: 13,670 adults were followed for a median of 9.0 years. During
      132,089 person years of follow-up 4040 subjects developed hypertension. Chilli
      consumption was inversely associated with the incidence of hypertension. The
      incidence rate of hypertension was 30.5, 33.4, 31.9, and 24.0 per 1000 person
      years among those who consumed no chilli or 1-20, 20.1-50, >=50.1 g/day
      respectively. Adjusting for age, gender, energy intake, sodium and fat intake,
      smoking, alcohol consumption and physical activity, those with increasing
      cumulative average chilli intake were less likely to develop hypertension: 0, 1
      20, 20.1-50 and >=50.1 g/day had a hazard ratio (HR) for hypertension of 1.00,
      0.80 (95%CI 0.73-0.88), 0.81 (0.73-0.89) and 0.65 (0.57-0.75) (p for trend
      <0.001) respectively. The association was independent of overall dietary patterns
      and BMI. There was no significant interaction between chilli intake and gender,
      income, education and residence (urban/rural) in relation to the risk of
      hypertension. CONCLUSIONS: Chilli intake is inversely associated with the risk of
      developing hypertension in Chinese adults.

PMID- 29460817
TI  - MaFOS-GDM trial: Maternal fish oil supplementation in women with gestational
      diabetes and cord blood DNA methylation at insulin like growth factor-1 (IGF-1)
      gene.
AB  - BACKGROUND: To evaluate the effects of maternal fish oil supplementation in women
      with gestational diabetes mellitus (GDM) on birthweight and DNA methylation at
      insulin like growth factor-1 (IGF-1) gene in their offspring. METHODS: Randomized
      controlled trial. A total of 120 women with GDM were randomized to one of the two
      groups between 24 and 28 weeks of the pregnancy: Group 1 (n = 52) received fish
      oil liquid softgel (Ocean plus(r)) and Group 2 (Placebo) (n = 68) sunflower oil
      liquid softgel. The birthweight and DNA methylation at IGF-1 gene of the
      offsprings were assessed. RESULTS: We observed a significant inverse association
      between fish oil use during pregnancy and birthweight (beta = -0.18, s.e.:125, P
      = .04), corresponding to a 250 g lower birthweight among infants born to fish oil
      users. This association didn't persist in multivariate analysis. Cord blood IGF-1
      was lower in fish oil group (P = .001). Cord blood DNA methylation percentages at
      CpG-1044 and CpG-611 sites of IGF-1 gene promoter 1 (P1) region were higher in
      fish oil group compared to placebo group (P = .02 and P = .001, respectively).
      However, CpG-1044 and CpG-611 methylations were not associated to birthweight
      (beta = 0.04, s.e: 25.1, P = .66 and beta = 0.04, s.e: 22.7, P = 0.66,
      respectively). CONCLUSIONS: Maternal fish oil use has small effects on
      birthweight and DNA methylation when given to mothers with GDM at late pregnancy.
      Future studies are needed to show associations between maternal fish oil use and
      neonatal DNA methylations. CLINICAL TRIAL REGISTRATION: "Fish Oil Supplementation
      in Women with Gestational Diabetes". IDENTIFIER: NCT02371343.

PMID- 29460818
TI  - Sarcopenic obesity and health outcomes in patients seeking weight loss treatment.
AB  - AIM: To investigate the prevalence of sarcopenic obesity (SO) and its association
      with health outcomes in patients seeking weight loss treatment from a bariatric
      center. METHODS: In this retrospective study, patients [>=18 years old, body mass
      index (BMI) >=30 kg/m2] from the Tallahassee Memorial Bariatric Center and with
      baseline body composition assessment by bioelectrical impedance analysis were
      included. Fat mass index (FMI = fat mass/height2) and fat-free mass index (FFMI =
      fat free mass/height2) were calculated. SO was defined by a FMI/FFMI ratio
      greater than the 95 percentile of sex, BMI and ethnicity specific population
      representative references. Medical records were reviewed for biochemical and
      comorbidity measures. RESULTS: One hundred and forty-four patients (~69% females,
      mean age 55.6 years, mean BMI 46.6 kg/m2) were included. Patients' FMI/FFMI
      ratios ranged from 0.35 to 1.60 kg/m2 across body weight spectrum, with 51%
      having SO. Blood pressure, fasting glucose, triglycerides, HDL or LDL were not
      different between patients with and without SO. However, the prevalence of high
      cholesterol, asthma, alcoholism and hernia were higher in patients with SO. SO
      was the strongest univariate predictor of high cholesterol (OR = 2.08, 95% CI
      1.07-4.04) and asthma (OR = 2.77, 95% CI = 1.12-6.83). CONCLUSION: SO was
      prevalent and associated with adverse health outcomes, beyond that captured by
      anthropometric measures in the present study.

PMID- 29460819
TI  - Effect of high dose vitamin D3 therapy on serum vitamin D3 levels in vitamin D
      insufficient adults with cystic fibrosis.
AB  - BACKGROUND: The effect of a high dose oral cholecalciferol repletion strategy in
      Vitamin D insufficient adults with CF is still unknown. Therefore, we assessed
      the effectiveness of our current approach, giving oral vitamin D3 supplementation
      at a dose of 10,000 IU from Monday to Friday for a total of 50,000 IU D3 weekly
      in vitamin D insufficient adult with CF. METHODS: We performed a retrospective
      chart review of all 59 adult CF patients between the ages of 17 and 64 years
      routinely followed at the CF Adult Program of Winnipeg Health Sciences Centre.
      Through consultation with the endocrinologist, our clinic vitamin D repletion
      protocol for treating CF adult patients who have serum 25-hydroxyvitamin D (25
      OHD) < 30 ng/ml (<75 nmol/L) was to prescribe vitamin D3 10,000 IU orally from
      Monday to Friday (or the weekly equivalent of 50,000 IU) for 12 weeks in addition
      to their regular CF vitamin that supplied from 800 to 2000 IU vitamin D3 daily.
      Cholecalciferol was conveniently administered orally as either one capsule (oil
      based) 10,000 IU or one tablet (powder-based) 10,000 IU. All patients were
      instructed to obtain follow-up serum 25-OHD levels post completion of treatment.
      RESULTS: Of the 59 adult patients at our CF Clinic, 35 patients (59%) had below
      optimal serum 25-OHD levels. Of the 35 patients identified, 10 patients with
      insufficient serum 25-OHD levels between 10 and 30 ng/ml (25-75 nmol/L) fulfilled
      the inclusion criteria. A significant increase in serum 25-OHD levels was
      observed (P < 0.01) from mean value of 21.6 +/- 5.9 ng/ml (54.1 +/- 14.8 nmol/L)
      at baseline to 31.7 +/- 9.1 ng/ml (79.3 +/- 22.8 nmol/L) >= 2 months post
      intervention. The current treatment approach was successful in treating Vitamin D
      insufficiency in 70% of the patients with low 25-OHD levels. CONCLUSION: The
      results of this study demonstrate that a large number of adults attending
      Winnipeg Health Sciences Centre CF Clinic have serum 25-OHD levels below 30 ng/ml
      (75 nmol/L). This supports the need for dedicated and individualized approach to
      manage this condition. High dose therapy of vitamin D3, although a more
      aggressive treatment approach, may result in achieving optimal levels of serum 25
      OHD in adults with CF.

PMID- 29460820
TI  - Association between mental disorders, cognitive disturbances and vitamin D serum
      level: Current state.
AB  - BACKGROUND & AIMS: Vitamin D deficiency has been identified as a global problem.
      Approximately 14% of the world population has inadequate vitamin D levels. This
      vitamin has been usually associated with bone disorders such as rickets,
      osteomalacia, and osteoporosis. However, these disorders present only a small
      part of all the disturbances which can be induced by its deficiency. Low serum
      vitamin D is associated with development of cardiovascular diseases,
      hypertension, neurodegenerative diseases, diabetes mellitus, metabolic syndrome
      and even cancer. This vitamin may be an important factor in the development of
      psychiatric illnesses, therefore clinicians should not leave this serious issue
      unresolved. The aim of this review is to describe the current data concerning the
      association between vitamin D serum levels, cognition and mental disorders.
      METHODS: We conducted a systematic bibliographical research, of PubMed, MedLine
      literature and Cochrane database without language restriction to identify all
      publications concerning this issue from 1995 to the first quarter of 2017.
      RESULTS: We found 48,937 articles concerning vitamin D, published during the last
      22 years and 3 months (1995-2017). We selected only those publications focused on
      the association between vitamin D serum deficiency and mental disturbances
      (depression, schizophrenia, cognitive disturbances, attention deficit disorder,
      and autism). One hundred and sixty-seven papers were found suitable to our
      selection criteria. Careful evaluation of the relevant literature demonstrates
      that addition of vitamin D to conventional antidepressive agents can improve
      antidepressive effect in contrast to placebo. Regarding other mental conditions
      there are no clear-cut conclusions. CONCLUSIONS: An association between low
      vitamin D serum levels and different mental disorders was found. Yet, nonetheless
      there is no clear consensus that addition of vitamin D improves or is related to
      a beneficial effect on mental health. More randomized clinical control trials
      should be performed in order to reach evidence based conclusions.

PMID- 29460822
TI  - Optimum Number of Sweeps in Clinical OVEMP Recording; How Many Sweeps are
      Necessary?
AB  - OBJECTIVE: Ocular vestibular-evoked myogenic potentials (OVEMPs) in our hands
      provide us with reproducible and consistent results; however, it has been shown
      that the OVEMP amplitude decreases with increased stimulus duration. The exact
      number of stimuli for OVEMP recording is not consistent among the published
      papers describing this test. We aimed to determine the number of stimuli needed
      to produce a satisfactory OVEMP response and the consequences of a more prolonged
      stimulation to the OVEMP response. MATERIALS AND METHODS: We retrospectively
      analyzed 50 OVEMP patient recordings and found that the average number of sweeps
      carried out was 26. We carried out three different OVEMP recordings using our
      standard protocol of (1) a "standard" OVEMP protocol, in which we record until
      the OVEMP wave becomes obvious; (2) an OVEMP recording using our average of 26
      sweeps; and (3) an OVEMP recording with twice as many sweeps. RESULTS: OVEMP
      latencies did not change when using different number of sweeps; however, the
      amplitudes showed a significant decrease with an increasing number of sweeps.
      CONCLUSION: OVEMPs can be completed in a satisfactory manner with a much lower
      number of stimuli than those usually carried out. Reducing the stimulus number
      reduces the time taken for the test, minimizes the cochlear insult while not
      reducing the valuable information obtained, and maximizes the amplitude of the
      stimulus, possibly increasing the accuracy of measuring interaural amplitudes and
      helping to measure asymmetry.

PMID- 29460823
TI  - Effect of Body Mass Index on Middle Ear Resonance Frequency.
AB  - OBJECTIVE: Multifrequency tympanometry (MFT) analyzes tympanograms obtained using
      different probe tones between 226 and 2000 Hz. An important parameter of MFT is
      resonance frequency (RF). Studies have recently demonstrated that the RF value
      can vary depending on many factors. To provide new data regarding MFT, middle ear
      RF values were investigated with regard to body mass index (BMI). MATERIALS AND
      METHODS: This study included 78 volunteers (i.e., 156 ears) aged 18-40 years who
      did not have hearing loss and whose otoscopic examinations were normal. Hearing
      thresholds were measured using pure tone audiometry, and RF values were recorded
      with immitansmetric measurements. The participants were divided into the
      following three groups according to their BMI: <18.5 kg/m2, Group 1; 18.5-24.9
      kg/m2, Group 2; and >25 kg/m2, Group 3. The RF values were also analyzed.
      RESULTS: Although there was no significant difference between Groups 1 and 2 in
      terms of RF values, a significant difference was observed between Groups 1 and 3
      and between Groups 2 and 3. CONCLUSION: In the light of these data, BMI values
      should be considered when middle ear RF values are assessed.

PMID- 29460824
TI  - Comparison of Cisplatin with Lipoplatin in Terms of Ototoxicity.
AB  - OBJECTIVE: Cisplatin (CDDP) is an anti-neoplastic agent that has been used in
      treatments of both pediatric and adult cancers. It has many side effects, such as
      ototoxicity, nephrotoxicity, and neurotoxicity. Lipoplatin (LIPO) is a
      nanomolecule with 110 nm diameter and composed of lipids and CDDP. In this study,
      we aimed to compare the toxic effects of LIPO with CDDP in the cochlear cells
      with anti-tumoral doses determined in neuroblastoma cells. MATERIALS AND METHODS:
      House Ear Institute Organ Corti 1 (HEI-OC1), MYC-N amplified KELLY, and MYC-N non
      amplified SH-SY5Y human neuroblastoma cells were used in this study. Firstly,
      anti-tumoral lethal dose 50 (LD50) of LIPO and CDDP were determined using the WST
      1 assay in both neuroblastoma cells. Then anti-tumoral doses of CDDP and LIPO
      were applied on HEI-OC1 cells for evaluating the toxic effects. The apoptotic
      cell death was measured using flow cytometric analysis of annexin-V/7-amino
      actinomycin (7-AAD) and cell cycle tests. RESULTS: LIPO or CDDP inhibited cell
      viability in a dose- and time-dependent manner in both neuroblastoma and HEI-OC1
      cells. LD50 values were selected as 20 mM for CDDP and 750 mM for LIPO in
      neuroblastoma cells. After the 48-hour incubation, KELLY cells treated with 20 mM
      CDDP and 750 mM LIPO had a 53% viability; SH-SY5Y cells treated 20 mM CDDP and
      750 mM LIPO had a 45% and 58% viability, respectively; and HEI-OC1 cells treated
      with 20 mM CDDP and 750 mM LIPO had a 65% and 82% viability, respectively.
      CONCLUSION: LIPO showed less toxic effects in the HEI-OC1 cells compared to CDDP
      at anti-tumoral doses.

PMID- 29460825
TI  - The Predictability Precision of Superior Semicircular Canal Through Radiological
      Assessment and Microanatomical Dissection.
AB  - OBJECTIVE: There is still ongoing research on the relationship of arcuate
      eminence (AE) and superior semicircular canal (SSC). We aimed to evaluate the
      precision of predictability of SSC through the morphology of AE via radiological
      means. MATERIALS AND METHODS: This investigation is performed on 12 dry skulls
      belonging to Mersin University Medical Faculty department of anatomy. Computed
      tomography (CT) assessment is performed with 0.5-mm-thin sections temporal bone
      algorithm on dry skulls which were marked with fixated copper wire by scotch
      tapes on the most prominent part of the middle fossa floor assuming the location
      of AE. The data are reformatted on the workstation with vitrea 2.0. The distances
      of the determined three points including lateral (A), apical (B), and medial (C)
      of the SSC and the copper wire are measured radiologically. Also, the height
      between the most apical part of the SSC to the floor of the skullbase (H) is
      measured. The angles between the placed copper wires and the SSC (E) are
      calculated. The angle between SSC and the midpoint of the IAC (F) and SSC to the
      sulcus of the greater GSPN (G) were measured. The nearest distance was measured
      between the most posterior part of the SSC and the point marked by the
      perpendicular line drawn from the medial border of the petrous bone to the most
      posterior part of the internal auditory canal (IAC) (D). RESULTS: The right and
      left A, B, and C distances are 2.54+/- 2.75, 3.67+/-3.16, 5.85+/-3.77; 2.92+/
      2.24, 3.68+/-2.93, 6.09+/-3.40, respectively. We could not find any statistical
      significance when the right A, B, and C distances were compared with the left
      values. Examination of the values revealed that C distance is greater than the A
      distance of the same side both for right (p=0.040) and left (p=0.022)
      measurements. The calculated left and right E angles are 30.313+/-12.838, and
      35.558+/-18.437 degrees, respectively. Statistical significance was not found
      between the right and left angles. The right and left F, G angles were 53.17,
      47.25; 93.58, 100.92 degrees; and D distances are 8.01, 8.13 millimeters,
      respectively. Statistical significance was not found when right and left E, F, G
      angles and D distances were compared. Among 12 left and 12 right sides, the
      copper wire was found to be nearly overlapping to SSC in two in the right and
      only one in the left. CONCLUSION: This study reveals that there is a great
      variability predicting the exact location of SSC through the prominence of AE.
      Complementary studies are needed with greater number of dry skulls and cadavers.
      Comparison of different hypothesis including the effect of temporal lobe sulcus
      is to be discussed to better enlighten the exact relationship of the
      aforementioned anatomical structures.

PMID- 29460826
TI  - Defining Clinical-Posturographic and Intra-Posturographic Discordances: What Do
      These Two Concepts Mean?
AB  - The European Society for Clinical Evaluation of Balance Disorders - ESCEBD -
      Executive Committee meets yearly to identify and address clinical equilibrium
      problems that are not yet well understood. This particular discussion addressed
      "discordances" (defined as "lack of agreement") in clinical assessment. Sometimes
      there is disagreement between a clinical assessment and measured abnormality
      (ies); sometimes the results within the assessment do not agree. This is
      sometimes thought of as "malingering" or an attempt to exaggerate what is wrong,
      but this is not always the case. The Committee discussed the clinical
      significance of unexpected findings in a patient's assessment. For example
      intraposturographic discordances sometimes exhibit findings (eg performance on
      more difficult trials may sometimes be better than on simpler trials). This can
      be suggestive of malingering, but in some situations can be a legitimate finding.
      The extreme malingerer and the genuine patient are at opposite ends of a spectrum
      but there are many variations along this spectrum and clinicians need to be
      cautious, as a posturography assessment may or may not be diagnostically helpful.
      Sometimes there is poor correlation between symptom severity and test results.
      Interpretation of posturography performance can at times be difficult and a
      patient's results must be correlated with clinical findings without stereotyping
      the patient. It is only in this situation that assessment in a diagnostic setting
      can be carried out in an accurate and unbiased manner.

PMID- 29460827
TI  - Repeated Attacks of Dizziness Caused by a Rare Mitochondrial Encephalomyopathy.
AB  - Cases of dizziness caused by multiple sclerosis are commonly reported, but those
      caused by mitochondrial encephalomyopathy have been rarely reported.
      Particularly, the description of eye nystagmography (ENG) using caloric and
      optokinetic nystagmus tests has not been reported to date. We encountered the
      case of a 40-year-old woman with mitochondrial encephalomyopathy who visited us
      with the chief complaint of dizziness. At first, we considered multiple sclerosis
      based on the magnetic resonance imaging (MRI) findings and dizziness. Repeated
      attacks of dizziness and serum lactic acid levels suggested mitochondrial
      encephalomyopathy. A muscle biopsy confirmed the diagnosis. ENG findings
      suggested central vestibular disorder of the cerebellum and brainstem. This case
      suggests that we should not rule out the differential diagnosis of a very rare
      mitochondrial encephalomyopathy in patients who experience dizziness with MRI
      findings indicative of multiple sclerosis.

PMID- 29460828
TI  - [Use of DNA-aptamers for enrichment of low abundant proteins in cellular extracts
      for quntitative detection by selected reaction monitoring].
AB  - The relationship between the amount of a target protein in a complex biological
      sample and its amount measured by selected reaction monitoring (SRM) mass
      spectrometry upon the affinity enrichment of target protein with aptamers
      immobilized on a solid phase was studied. Human thrombin added in known
      concentrations to cellular extracts derived from bacterial cells was used as
      model target protein. It has been demonstrated that the affinity enrichment of
      thrombin in cellular extracts by means of the thrombin-binding aptamer
      immobilized on the surface of magnetic microbeads results in an approximately 10
      fold increase of the concentration of target protein and a 100-fold decrease of
      the low limit of a target protein concentration range where its quantitative
      detection by SRM is possible without an interference from other peptides present
      in a tryptic digest.

PMID- 29460829
TI  - [Quality control study of engineered skin tissue].
AB  - OMERO service was used to annotate the cell line HaCaT microscope images by two
      independent expert groups. The images were obtained in the course of developing
      tissue-engineered epithelium which consisted of several layers of the
      keratinocytes. Evaluation of expert opinions was performed by calculation of
      specificity, sensitivity and accuracy. The best convergence of opinions (91%) was
      achieved for the confluence of the cell monolayers. Accuracy 70% was observed in
      determining the extent of cell differentiation after 10 days of incubation. The
      paper illustrates the usefulness of OMERO service for dynamic cross-validation of
      quality in the development and standardization of cell preparations.

PMID- 29460830
TI  - [Exocytosis of myeloperoxidase from activated neutrophils in the presence of
      heparin].
AB  - Exocytosis of myeloperoxidase (MPO) from activated neutrophils in the presence of
      the anionic polysaccharide heparin was studied. It was determined that the
      optimal concentration of heparin (0.1 u/ml), at which there is no additional
      activation of cells (absence of amplification of exocytosis of lysozyme contained
      in specific and azurophilic granules). It was found that after preincubation of
      cells with heparin (0.1 u/ml) the exocytosis of MPO from neutrophils activated by
      various stimulants (fMLP, PMA, plant lectins CABA and PHA-L) increased compared
      to that under the action of activators alone. In addition, it was shown that
      heparin in the range of concentrations 0.1-50 u/ml did not affect on the
      peroxidase activity of the MPO isolated from leukocytes. Thus, the use of heparin
      at a concentration of 0.1 u/ml avoids the artifact caused by the "loss" of MPO in
      a result of its binding to neutrophils, and increases the accuracy of the method
      of registration the degranulation of azurophilic granules of neutrophils based on
      determination of the concentration or peroxidase activity of MPO in cell
      supernatants.

PMID- 29460831
TI  - [Isolation of extracellular micro-vesicles from cell culture medium: comparative
      evaluation of methods].
AB  - Extracellular vesicles (EV) are secreted by cells of multicellular organisms. EV
      mediate specific mode of intercellular communication by "horizontal" exchange of
      substances and information. This phenomenon seems to have an essential biological
      significance and became a subject of intensive research. Biogenesis, structural
      and functional features of the EV is being commonly studies in in vitro
      condition. Several methods of EV isolation from cell culture medium are
      established, however selection of method might influence on obtained results. The
      choice of the optimal method depends usually from the amount of medium and the
      aims of the research while is still challenging issue. We performed a comparative
      analysis of four different methods of EV isolation from cell culture medium:
      differential ultracentrifugation, ultracentrifugation with a 30% sucrose/D2O
      "cushion", precipitation with plant proteins and immune-affinity capturing. EV
      isolated by different approaches were compared in terms of following parameters:
      size, concentration, morphology of EV, contamination by non-vesicular particles,
      content of exosomal tetraspanins on the EV surface, content of total proteins,
      RNA, and several glioma-associated miRNAs. Applied methods included nano-patricle
      tracking analysis (NTA), dynamic light scattering (DLS), cryo-electron
      microscopy, flow cytometry and RT-qPCR. On the base of obtained results, we
      developed practical recommendations that may help researchers to make a best
      choice of EV isolation method.

PMID- 29460832
TI  - [The effect of the biologically active additive epiphamine on antioxidant and
      NADPH-generating enzymes activity under experimental cerebral
      ischemia/reperfusion in rats].
AB  - The effect of biologically active additive with immunomodulator properties
      epiphamine on the activity of antioxidant (superoxide dismutase, catalase,
      glutathione peroxidase, glutathione reductase, glutathione transferase) and NADPH
      generating (glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase)
      enzymes has been investigated at experimental cerebral ischemia/reperfusion in
      rats. The results obtained indicate epiphamine-induced changes of these enzymes
      activities towards control values. Changes in the content of lactate, a marker of
      the pathology development, have also been found in experimental animals under
      ischemia and epiphamine administration caused changes similar to those observed
      in the case of enzyme activities studied. In most cases, the changes were dose
      dependent. Thus, epiphamine can be of considerable interest from the point of
      view of metabolic changes pharmacological correction at the development of the
      pathology accompanied by oxidative stress.

PMID- 29460833
TI  - [Representation analysis of miRNA from clarified urine and urine microvesicles in
      prostate malignancies and non-malignant neoplasms].
AB  - Urine of prostate cancer patients contains tumor-specific biopolymers, including
      protein- and microvesiclesassociated miRNAs that can potentially be used as
      oncomarkers. Previously we have characterized urine extracellular vesicles and
      demonstrated diagnostic potential of their miRNA cargo. In this study, we have
      performed a comparative analysis of the expression of 84 miRNA in paired samples
      of urine microvesicles and clarified urine from healthy men, patients with benign
      hyperplasia and cancer of the prostate using miRCURY LNA miRNA qPCR Panels.
      Subsets of miRNAs with differences in expression between the fractions of the
      urine were found in all three groups. Two groups of miRNA were identified based
      on the patterns of their differential expression. They regulate several key
      signaling pathways associated with prostate cancer development.

PMID- 29460834
TI  - [Comparison of matrix proteinase mRNA expression in morphologically normal,
      neoplastic, and metastatic colon tissue and colon biopsies from healthy donors].
AB  - Matrix metalloproteinases (MMPs) responsible for the extracellular matrix
      remodeling, the activation of various growth factors, and angiogenesis play an
      important role in the colorectal cancer (CRC) development. In the present work
      the comparative analysis of MMP-7, -8, -9, and -11 mRNA as well mRNA of the Ki-67
      proliferation marker in tissue samples obtained from CRC patients and healthy
      individuals. Employing the real time PCR method the expression levels of several
      MMPs (MMP-7, -8, -9, and -11) and cell proliferation marker, Ki-67, were
      simultaneously measured in 256 tissue samples obtained from 112 patients with
      CRC: 112 samples of the primary tumor (CRC), 112 samples of the most distant
      border of morphologically normal colonic mucosa (MNT), 16 samples of liver
      metastases) and from 16 healthy volunteers who underwent colonoscopy and biopsy.
      The expression of both MMPs studied and Ki-67 was found to be elevated in CRC
      primary tumors and liver metastases compared with the normal mucosa. CRC tumor
      and metastatic cells exhibited similar proliferative activity. The metastases are
      characterized by the highest cross-correlation of MMPs among tissue types tested.
      For the first time it was shown that normal mucosa from healthy individuals and
      CRC patients varied in the MMP-8 expression level. They also had dissimilar MMP
      correlation patterns thus suggesting that epithelial cells adjusted to CRC tumor
      differ from mucosal epithelial cells of healthy individuals.

PMID- 29460835
TI  - [Construction and characterization of a recombinant mutant homolog of the CheW
      protein from Thermotoga petrophila RKU-1].
AB  - In the work a recombinant chemotaxis protein CheW from Thermotoga petrophila RKU
      1 (TpeCheW) and its mutant homolog (TpeCheW-mut) were created. It was shown that,
      despite the low homology with CheW prototypes from intestinal bacteria, these
      proteins didn't cause metabolic overload and were well expressed by cells of E.
      coli laboratory strains. We have discovered a broad spectrum of industrial
      valuable properties of the TpeCheW-mut protein such as stability in a wide range
      of temperatures and pH, high expression level, solubility and possibility of the
      application of a simple low-stage purification methodology with the use of
      preliminary heat treatment. Possible directions of the scientific and industrial
      application of this protein were claimed.

PMID- 29460836
TI  - [Study specificity of isatin interactions with P450 cytochromes].
AB  - Cytochrome P450-dependent monooxygenase systems exist basically in all living
      organisms, where they perform various important functions. The coordinated
      functioning of these systems involves many proteins participating in different
      protein-protein interactions (PPI). Previously, we have found that the endogenous
      non-peptide bioregulator isatin (indoledione-2,3), synthesized from indole by
      means of certain cytochromes P450 (e.g. P450 2E1, P450 2C19, P450 2A6) regulates
      affinity of some PPI. In this work, an attempt has been undertaken to register a
      direct interaction of isatin with a set of different proteins related to the
      functioning of cytochrome P450-dependent monooxygenase: five isoforms of
      cytochromes P450, two isoforms of cytochrome b5, cytochrome P450 reductase,
      adrenodoxin, adrenodoxin reductase and ferrochelatase. The study has shown that
      isatin binds specifically only to cytochromes P450 with high affinity (the
      equilibrium dissociation constant (Kd) is about 10-8 M).

PMID- 29460837
TI  - [Pharmacological targets for dislipidemies correction. Opportunities and
      prospects of therapeutic usage].
AB  - Literature data on influence of existing and new groups of drug preparations for
      dyslipidemias correction are systemized, and molecular mechanisms of their
      effects are reviewed. The results of experimental and clinical investigations
      aimed at revealing of new pharmacological targets of dyslipidemias correction
      were analyzed. The approaches for activation of high density lipoproteins
      functionality are described. The implementation of alternative preparations with
      new alternative mechanisms of action may be suggested to improve the
      effectiveness of traditional treatment in the future.

PMID- 29460838
TI  - [Phospholipase D: its role in metabolism processes and disease development].
AB  - Phospholipase D (PLD) is one of the key enzymes that catalyzes the hydrolysis of
      cell membrane phospholipids. In this review current knowledge about six human PLD
      isoforms, their structure and role in physiological and pathological processes is
      summarized. Comparative analysis of PLD isoforms structure is presented. The
      mechanism of the hydrolysis and transphosphatidylation performed by PLD is
      described. The PLD1 and PLD2 role in the pathogenesis of some cancer, infectious,
      thrombotic and neurodegenerative diseases is analyzed. The prospects of PLD
      isoform-selective inhibitors development are shown in the context of the clinical
      usage and the already-existing inhibitors are characterized. Moreover, the
      formation of phosphatidylethanol (PEth), the alcohol abuse biomarker, as the
      result of PLD-catalyzed phospholipid transphosphatidylation is considered.

PMID- 29460839
TI  - [Molecular mechanism of amyloid formation by Ab peptide: review of own works].
AB  - TA characteristic feature of amyloid structures is polymorphism. The study of
      amyloid structures and their formation process was carried out for synthetic and
      recombinant Ab(1-40) and Ab(1-42) peptide preparations. In the study of these
      peptides, we recognized fibrils of different morphologies. We observed fibrillar
      formations in the form of single fibrils, ribbons, bundles, bunches, and
      clusters. Polymorphism of fibrils was observed not only when the environmental
      conditions changed, but under the same conditions and this was a common
      characteristics of all amyloid formations. Fibrils of Ab(1-40) peptides tended to
      form aggregates of fibrils in the form of ribbons, while Ab(1-42) peptide under
      the same conditions polymerized in the form of rough fibrils of different
      diameters and tends to branch. We assume that the formation of fibrils of Ab(1
      40) and Ab(1-42) peptides occurs according to a simplified scheme: a destabilized
      monomer (r) a ring oligomer (r) a mature fibril consisting of ring oligomers.
      Proceeding from the proposition that the ring oligomer is the main building block
      of amyloid fibril (similar to the cell in the body), it is easy to explain fibril
      polymorphism, as well as fragmentation of mature fibrils under various external
      influences, branching and irregularity of diameter (surface roughness) of
      fibrils. One aspect of the study of amyloidogenesis is the determination of the
      regions of the protein chain forming the core of the amyloid fibril. We
      theoretically predicted amyloidogenic regions for two isoforms of Ab peptides
      capable of forming an amyloid structure: 16-21 and 32-36 residues. Using the
      method of tandem mass spectrometry, these regions were determined experimentally.
      It was shown that the regions of Ab(1-40) peptide from 16 to 22 and from 28 to 40
      residues were resistant to the action of proteases, i.e. its formed the core of
      the amyloid fibril. For Ab(1-42) peptide the whole sequence is not available for
      the action of proteases, which indicates a different way of associating ring
      oligomers in the formation of fibrils. Based on electron microscopy and mass
      spectrometry data we proposed a molecular model of the fibril formed by Ab(1-40)
      and Ab(1-42) peptides.

PMID- 29460840
TI  - [Comparative sub-population analysis of exosomes from blood plasma of cancer
      patients].
AB  - To increase the sensitivity and specificity of the developed methods for
      diagnosis of oncological diseases using exosomes of blood, a stage of pre
      selection of tumor exosomes from a common pool of circulating microvesicles is
      required. In the present work, universal proteins have been identified, their
      expression has been increased in the exosomes of patients with colorectal cancer,
      head and neck squamous cell carcinomas, and lung cancer. The use of antibodies
      against major exosomal proteins will further develop a simple and high
      performance method of affinity isolation of tumor exosomes.

PMID- 29460841
TI  - [Possibility of application of extracellular protease of micromycet Aspergillus
      ochraceus VKM F-4104D for determination of protein C content in human blood
      plasma].
AB  - It was shown that the activator activity of protein C, determined in normal
      plasma using Aspergillus ochraceus protease, is comparable with the activity of
      commercial protease analogue from the South American copperhead venom (ProtacO).
      It was found that protease of A. ochraceus can be used to determine protein C in
      plasma with its reduced content similar to ProtacO. Comparison of the activator
      protein C activity of A. ochraceus protease and the commercial analogue showed
      some excess of the activator activity of the fungal preparation, which may make
      it a promising substitute for the snake activator in diagnostical kits for
      determining the protein C content in clinical laboratories.

PMID- 29460843
TI  - Breakdown of the coherence effects and Fermi liquid behavior in YbAl3
      nanoparticles.
AB  - A change in the Kondo lattice behavior of bulk YbAl3 has been observed when the
      alloy is shaped into nanoparticles (~12 nm). Measurements of the electrical
      resistivity show inhibited coherence effects and deviation from the standard
      Fermi liquid behavior (T 2-dependence). These results are interpreted as being
      due to the effect of the disruption of the periodicity of the array of Kondo ions
      provoked by the size reduction process. Additionally, the ensemble of randomly
      placed nanoparticles also triggers an extra source of electronic scattering at
      very low temperatures (~15 K) due to quantum interference effects.

PMID- 29460844
TI  - Theoretical investigation of excitonic magnetism in LaSrCoO4.
AB  - We use the LDA+U approach to search for possible ordered ground states of
      LaSrCoO4. We find a staggered arrangement of magnetic multipoles to be stable
      over a broad range of Co 3d interaction parameters. This ordered state can be
      described as a spin-density-wave-type condensate of [Formula: see text] excitons
      carrying spin S  =  1. Further, we construct an effective strong-coupling model,
      calculate the exciton dispersion and investigate closing of the exciton gap,
      which marks the exciton condensation instability. Comparing the layered LaSrCoO4
      with its pseudo cubic analog LaCoO3, we find that for the same interaction
      parameters the excitonic gap is smaller (possibly vanishing) in the layered
      cobaltite.

PMID- 29460845
TI  - Thermal expansion of quaternary nitride coatings.
AB  - The thermal expansion coefficient of technologically relevant multicomponent
      cubic nitride alloys are predicted using the Debye model with ab initio elastic
      constants calculated at 0 K and an isotropic approximation for the Gruneisen
      parameter. Our method is benchmarked against measured thermal expansion of TiN
      and Ti(1-x)Al x N as well as against results of molecular dynamics simulations.
      We show that the thermal expansion coefficients of Ti(1-x-y)X y Al x N (X  =  Zr,
      Hf, Nb, V, Ta) solid solutions monotonously increase with the amount of alloying
      element X at all temperatures except for Zr and Hf, for which they instead
      decrease for [Formula: see text].

PMID- 29460842
TI  - Engineering principles for guiding spheroid function in the regeneration of bone,
      cartilage, and skin.
AB  - There is a critical need for strategies that effectively enhance cell viability
      and post-implantation performance in order to advance cell-based therapies.
      Spheroids, which are dense cellular aggregates, overcome many current limitations
      with transplanting individual cells. Compared to individual cells, the
      aggregation of cells into spheroids results in increased cell viability, together
      with enhanced proangiogenic, anti-inflammatory, and tissue-forming potential.
      Furthermore, the transplantation of cells using engineered materials enables
      localized delivery to the target site while providing an opportunity to guide
      cell fate in situ, resulting in improved therapeutic outcomes compared to
      systemic or localized injection. Despite promising early results achieved by
      freely injecting spheroids into damaged tissues, growing evidence demonstrates
      the advantages of entrapping spheroids within a biomaterial prior to
      implantation. This review will highlight the basic characteristics and qualities
      of spheroids, describe the underlying principles for how biomaterials influence
      spheroid behavior, with an emphasis on hydrogels, and provide examples of
      synergistic approaches using spheroids and biomaterials for tissue engineering
      applications.

PMID- 29460846
TI  - Construction of a liver sinusoid based on the laminar flow on chip and self
      assembly of endothelial cells.
AB  - The liver is one of the main metabolic organs, and nearly all ingested drugs will
      be metabolized by the liver. Only a small fraction of drugs are able to come onto
      the market during drug development, and hepatic toxicity is a major cause for
      drug failure. Since drug development is costly in both time and materials, an in
      vitro liver model that can accelerate bioreactions in the liver and reduce drug
      consumption is imperative in the pharmaceutical industry. The liver on a chip is
      an ideal alternative for its controllable environment and tiny size, which means
      constructing a more biomimetic model, reducing material consumption as well as
      promoting drug diffusion and reaction. In this study, taking advantage of the
      laminar flow on chips and using natural degradable gel rat tail Collagen-I, we
      constructed a liver sinusoid on a chip. By synchronously injecting two kinds of
      cell-laden collagen, HepG2-laden collagen and HUVEC-laden collagen, we formed two
      collagen layers with a clear borderline. By controlling the HUVEC density and
      injection of growth factors, HUVECs in collagen formed a monolayer through self
      assembly. Thus, a liver sinusoid on a chip was achieved in a more biomimetic
      environment with a more controllable and uniform distribution of discrete HUVECs.
      Viability, album secretion and urea synthesis of the live sinusoid on a chip were
      analysed on days 3, 5 and 7 after collagen injection with acetaminophen treatment
      at 0 (control), 10 and 20 mM. The results indicated that our liver sinusoid on a
      chip was able to maintain bioactivity and function for at least 7 d and was
      beneficial for hepatotoxic drug screening.

PMID- 29460847
TI  - Local order and crystallization of dense polydisperse hard spheres.
AB  - Computer simulations give precious insight into the microscopic behavior of
      supercooled liquids and glasses, but their typical time scales are orders of
      magnitude shorter than the experimentally relevant ones. We recently closed this
      gap for a class of models of size polydisperse fluids, which we successfully
      equilibrate beyond laboratory time scales by means of the swap Monte Carlo
      algorithm. In this contribution, we study the interplay between compositional and
      geometric local orders in a model of polydisperse hard spheres equilibrated with
      this algorithm. Local compositional order has a weak state dependence, while
      local geometric order associated to icosahedral arrangements grows more markedly
      but only at very high density. We quantify the correlation lengths and the degree
      of sphericity associated to icosahedral structures and compare these results to
      those for the Wahnstrom Lennard-Jones mixture. Finally, we analyze the structure
      of very dense samples that partially crystallized following a pattern
      incompatible with conventional fractionation scenarios. The crystal structure has
      the symmetry of aluminum diboride and involves a subset of small and large
      particles with size ratio approximately equal to 0.5.

PMID- 29460848
TI  - Quantum phase transition and non-Fermi liquid behavior in Fe1-x Co x Si (x ?
      0.7).
AB  - We report on the nature of electron correlations in Fe1-x Co x Si ([Formula: see
      text]) using combined results of magnetization, specific heat and transport
      properties. Doping driven quantum critical point is observed to occur at
      [Formula: see text]. The magnetically unstable regime is identified to be
      centered around [Formula: see text] [[Formula: see text]]. The emergence of non
      Fermi liquid behaviors in x  =  0.8 (near to ferromagnetic quantum critical
      point) and x  =  0.9 (disorder-induced) compositions are discussed on the basis
      of the power-law dependence of susceptibility [Formula: see text] ([Formula: see
      text] for x  =  0.8 and 0.55 for x  =  0.9), specific heat [Formula: see text]
      ([Formula: see text] for x  =  0.8 and 0.9) and resistivity [Formula: see text]
      ([Formula: see text] for x  =  0.8 and 1.38 for x  =  0.9). Further, a
      comprehensive classification of doping dependent physical properties of Fe1-x Co
      x Si is presented in the revisited temperature-composition (T-x) phase diagram.

PMID- 29460850
TI  - Self consistent field theory of virus assembly.
AB  - The ground state dominance approximation (GSDA) has been extensively used to
      study the assembly of viral shells. In this work we employ the self-consistent
      field theory (SCFT) to investigate the adsorption of RNA onto positively charged
      spherical viral shells and examine the conditions when GSDA does not apply and
      SCFT has to be used to obtain a reliable solution. We find that there are two
      regimes in which GSDA does work. First, when the genomic RNA length is long
      enough compared to the capsid radius, and second, when the interaction between
      the genome and capsid is so strong that the genome is basically localized next to
      the wall. We find that for the case in which RNA is more or less distributed
      uniformly in the shell, regardless of the length of RNA, GSDA is not a good
      approximation. We observe that as the polymer-shell interaction becomes stronger,
      the energy gap between the ground state and first excited state increases and
      thus GSDA becomes a better approximation. We also present our results
      corresponding to the genome persistence length obtained through the tangent
      tangent correlation length and show that it is zero in case of GSDA but is equal
      to the inverse of the energy gap when using SCFT.

PMID- 29460849
TI  - Calculations of spin-polarized Goos-Hanchen displacement in magnetically confined
      GaAs/Al x Ga1-x As nanostructure modulated by spin-orbit couplings.
AB  - We theoretically investigate Goos-Hanchen (GH) displacement by modelling the spin
      transport in an archetypal device structure-a magnetically confined GaAs/Al x Ga1
      x As nanostructure modulated by spin-orbit coupling (SOC). Both Rashba and
      Dresselhaus SOCs are taken into account. The degree of spin-polarized GH
      displacement can be tuned by Rashba or Dresselhaus SOC, i.e. interfacial
      confining electric field or strain engineering. Based on such a semiconductor
      nanostructure, a controllable spatial spin splitter can be proposed for
      spintronics applications.

PMID- 29460851
TI  - Robust tunable excitonic features in monolayer transition metal dichalcogenide
      quantum dots.
AB  - The effects of quantum confinement on excitons in parabolic quantum dots of
      monolayer transition metal dichalcogenides (TMDC QDs) are investigated within a
      massive Dirac fermion model. A giant spin-valley coupling of the TMDC QDs is
      obtained, larger than that of monolayer TMDC sheets and consistent with recent
      experimental measurements. The exciton transition energy and the binding energy
      are calculated, and it is found that the strong quantum confinement results in
      extremely high exciton binding energies. The enormously large exciton binding
      energy in TMDC QDs ([Formula: see text] for different kinds of TMDC QDs) ensures
      that the many body interactions play a significant role in the investigation of
      the optical properties of these novel nanostructures. The estimated oscillator
      strength and radiative lifetime of excitons are strongly size-dependent and
      indicate a giant oscillator strength enhancement and ultrafast radiative
      annihilation of excitons, varying from a few tens of femtoseconds to a few
      picoseconds. We found that the spin-dependent band gap, spin-valley coupling,
      binding energy and excitonic effects can be tuned by quantum confinements,
      leading to tunable quantum dots in monolayer TMDCs. This finding offers new
      functionality in engineering the interaction of a 2D material with light and
      creates promise for the quantum manipulation of spin and valley degrees of
      freedom in TMDC nanostructures, enabling versatile novel 2D quantum photonic and
      optoelectronic nanodevices.

PMID- 29460852
TI  - Friction fluctuations of gold nanoparticles in the superlubric regime.
AB  - Superlubricity, or alternatively termed structural (super)lubrictiy, is a concept
      where ultra-low friction is expected at the interface between sliding surfaces if
      these surfaces are incommensurate and thus unable to interlock. In this work, we
      now report on sudden, reversible, friction changes that have been observed during
      AFM-based nanomanipulation experiments of gold nanoparticles sliding on highly
      oriented pyrolythic graphite. These effects can be explained by rotations of the
      gold nanoparticles within the concept of structural superlubricity, where the
      occurrence of ultra-low friction can depend extremely sensitively on the relative
      orientation between the slider and the substrate. From our theoretical
      simulations it will become apparent how even miniscule magnitudes of rotation are
      compatible to the observed effects and how size and shape of the particles can
      influence the dependence between friction and relative orientation.

PMID- 29460853
TI  - On-surface synthesis on a bulk insulator surface.
AB  - On-surface synthesis has rapidly emerged as a most promising approach to prepare
      functional molecular structures directly on a support surface. Compared to
      solution synthesis, performing chemical reactions on a surface offers several
      exciting new options: due to the absence of a solvent, reactions can be
      envisioned that are otherwise not feasible due to the insolubility of the
      reaction product. Perhaps even more important, the confinement to a two
      dimensional surface might enable reaction pathways that are not accessible
      otherwise. Consequently, on-surface synthesis has attracted great attention in
      the last decade, with an impressive number of classical reactions transferred to
      a surface as well as new reactions demonstrated that have no classical analogue.
      So far, the majority of the work has been carried out on conducting surfaces.
      However, when aiming for electronic decoupling of the resulting structures, e.g.
      for the use in future molecular electronic devices, non-conducting surfaces are
      highly desired. Here, we review the current status of on-surface reactions
      demonstrated on the (10.4) surface of the bulk insulator calcite. Besides
      thermally induced C-C coupling of halogen-substituted aryls, photochemically
      induced [2  +  2] cycloaddition has been proven possible on this surface.
      Moreover, experimental evidence exists for coupling of terminal alkynes as well
      as diacetylene polymerization. While imaging of the resulting structures with
      dynamic atomic force microscopy provides a direct means of reaction verification,
      the detailed reaction pathway often remains unclear. Especially in cases where
      the presence of metal atoms is known to catalyze the corresponding solution
      chemistry reaction (e.g. in the case of the Ullmann reaction), disclosing the
      precise reaction pathway is of importance to understand and generalize on-surface
      reactivity on a bulk insulator surface. To this end, density-functional theory
      calculations have proven to provide atomic-scale insights that have greatly
      contributed to unravelling the details of on-surface synthesis on a bulk
      insulator surface.

PMID- 29460854
TI  - Band structure and unconventional electronic topology of CoSi.
AB  - Semimetals with certain crystal symmetries may possess unusual electronic
      structure topology, distinct from that of the conventional Weyl and Dirac
      semimetals. Characteristic property of these materials is the existence of band
      touching points with multiple (higher than two-fold) degeneracy and nonzero Chern
      number. CoSi is a representative of this group of materials exhibiting the so
      called 'new fermions'. We report on an ab initio calculation of the electronic
      structure of CoSi using density functional methods, taking into account the spin
      orbit interactions. The linearized [Formula: see text] Hamiltonian, describing
      the anisotropic electronic structure of CoSi near the Gamma point is derived. The
      topological features of band-touching nodes with four- and six-fold degeneracy
      located at the Gamma and R points in the first Brillouin zone are analysed using
      the linearized Hamiltonians and first principle calculations. In particular, we
      show, using the non-Abelian Berry curvature, that these band-touching points
      carry topological charges of [Formula: see text], which change signs at certain
      values of parameters of the Hamiltonians. We describe the resulting Fermi arc
      surface states and their spin texture. We also discuss the influence of many body
      [Formula: see text] corrections on the electronic band structure and the
      topological properties of CoSi.

PMID- 29460855
TI  - Many-body perturbation theory for understanding optical excitations in organic
      molecules and solids.
AB  - Semiconductors composed of organic molecules are promising as components for
      flexible and inexpensive optoelectronic devices, with many recent studies aimed
      at understanding their electronic and optical properties. In particular,
      computational modeling of these complex materials has provided new understanding
      of the underlying properties which give rise to their excited-state phenomena.
      This article provides an overview of recent many-body perturbation theory (MBPT)
      studies of optical excitations within organic molecules and solids. We discuss
      the accuracy of MBPT within the GW/BSE approach in predicting excitation energies
      and absorption spectra, and assess the impact of two commonly used
      approximations, the DFT starting point and the Tamm-Dancoff approximation.
      Moreover, we summarize studies that elucidate the role of solid-state structure
      on the nature of excitons in organic crystals. These studies show that a rich
      physical understanding of organic materials can be obtained from GW/BSE.

PMID- 29460856
TI  - Ultraviolet photoelectron spectroscopy reveals energy-band dispersion for pi
      stacked 7,8,15,16-tetraazaterrylene thin films in a donor-acceptor bulk
      heterojunction.
AB  - 7,8,15,16-tetraazaterrylene (TAT) thin films grown on highly oriented pyrolytic
      graphite (HOPG) substrates were studied extensively with regard to their
      intrinsic and interfacial electronic properties by means of ultraviolet
      photoelectron spectroscopy (UPS). Merely weak substrate-adsorbate interaction
      occurs at the TAT/HOPG interface, with interface energetics being only little
      affected by the nominal film thickness. Photon energy-dependent UPS performed
      perpendicular to the molecular planes of TAT multilayer films at room temperature
      clearly reveals band-like intermolecular dispersion of the TAT highest occupied
      molecular orbital (HOMO) energy. Based on a comparison with a tight-binding
      model, a relatively narrow bandwidth of 54 meV is derived, which points to the
      presence of an intermediate regime between hopping and band-like hole transport.
      Upon additional deposition of 2,2':5',2":5",2"'-quaterthiophene (4T), a 4T:TAT
      donor-acceptor bulk heterojunction with a considerable HOMO-level offset at the
      donor-acceptor interface is formed. The 4T:TAT bulk heterojunction likewise
      exhibits intermolecular dispersion of the TAT HOMO energy, yet with a significant
      decreased bandwidth.

PMID- 29460857
TI  - New developments in laser-based photoemission spectroscopy and its scientific
      applications: a key issues review.
AB  - The significant progress in angle-resolved photoemission spectroscopy (ARPES) in
      last three decades has elevated it from a traditional band mapping tool to a
      precise probe of many-body interactions and dynamics of quasiparticles in complex
      quantum systems. The recent developments of deep ultraviolet (DUV, including
      ultraviolet and vacuum ultraviolet) laser-based ARPES have further pushed this
      technique to a new level. In this paper, we review some latest developments in
      DUV laser-based photoemission systems, including the super-high energy and
      momentum resolution ARPES, the spin-resolved ARPES, the time-of-flight ARPES, and
      the time-resolved ARPES. We also highlight some scientific applications in the
      study of electronic structure in unconventional superconductors and topological
      materials using these state-of-the-art DUV laser-based ARPES. Finally we provide
      our perspectives on the future directions in the development of laser-based
      photoemission systems.

PMID- 29460858
TI  - Aedes vittatus (Bigot) mosquito: An emerging threat to public health.
AB  - Aedes vittatus (Bigot) mosquito is a voracious biter of humans and has a
      geographical distribution throughout tropical Asia, Africa and the Mediterranean
      region of Europe. It is predominantly a rock-hole breeder, though it can breed in
      diverse macro- and micro-habitats. The mosquito plays an important role in the
      maintenance and transmission of yellow fever (YFV), dengue (DENV), chikungunya
      (CHIKV) and Zika (ZIKV) viruses. It has been implicated as an important vector of
      YFV in several African countries as evidenced by repeated virus isolations from
      the mosquito and its potential to transmit the virus experimentally. Similarly,
      DENV-2 has been isolated from wild caught Ae. vittatus mosquitoes in Senegal,
      Africa which has been shown to circulate the virus in sylvatic populations
      without causing human infection. Experimental studies have shown replication of
      the virus at a low scale in naturally infected mosquitoes while high rate of
      infection and dissemination have been reported in parenterally infected
      mosquitoes. Natural isolation of ZIKV has been reported from Senegal and Cote
      d'Ivoire from these mosquitoes. They were found highly competent to transmit the
      virus experimentally and the transmission rate is at par with Ae. leuteocephalus,
      the primary vector of ZIKV. A few CHIKV isolations have also been reported from
      the mosquitoes in Senegal and other countries in Africa. Experimental studies
      have demonstrated high susceptibility, early dissemination and efficient
      transmission of CHIKV by Ae. vittatus mosquitoes. The mosquitoes with their high
      susceptibility and competence to transmit important viruses, viz. YFV, DENV,
      CHIKV and ZIKV pose a major threat to public health due to their abundance and
      anthropophilic behaviour.

PMID- 29460859
TI  - Improving vector-borne pathogen surveillance: A laboratory-based study exploring
      the potential to detect dengue virus and malaria parasites in mosquito saliva.
AB  - Background & objectives: Vector-borne pathogen surveillance programmes typically
      rely on the collection of large numbers of potential vectors followed by
      screening protocols focused on detecting pathogens in the arthropods. These
      processes are laborious, time consuming, expensive, and require screening of
      large numbers of samples. To streamline the surveillance process, increase sample
      throughput, and improve cost-effectiveness, a method to detect dengue virus and
      malaria parasites (Plasmodium falciparum) by leveraging the sugar-feeding
      behaviour of mosquitoes and their habit of expectorating infectious agents in
      their saliva during feeding was investigated in this study. Methods: Dengue virus
      2 (DENV-2) infected female Aedes aegypti mosquitoes and P. falciparum infected
      female Anopheles stephensi mosquitoes were allowed to feed on honey coated
      Flinders Technical Associates -FTA(r) cards dyed with blue food colouring. The
      feeding resulted in deposition of saliva containing either DENV-2 particles or P.
      falciparum sporozoites onto the FTA card. Nucleic acid was extracted from each
      card and the appropriate real-time PCR (qPCR) assay was run to detect the
      pathogen of interest. Results: As little as one plaque forming unit (PFU) of DENV
      2 and as few as 60 P. falciparum parasites deposited on FTA cards from infected
      mosquitoes were detected via qPCR. Hence, their use to collect mosquito saliva
      for pathogen detection is a relevant technique for vector surveillance.
      Interpretation & conclusion: This study provides laboratory confirmation that FTA
      cards can be used to capture and stabilize expectorated DENV-2 particles and P.
      falciparum sporozoites from infectious, sugar-feeding mosquitoes in very low
      numbers. Thus, the FTA card-based mosquito saliva capture method offers promise
      to overcome current limitations and revolutionize traditional mosquito-based
      pathogen surveillance programmes. Field testing and further method development
      are required to optimize this strategy.

PMID- 29460860
TI  - Aetiology of acute encephalitis syndrome in Uttar Pradesh, India from 2014 to
      2016.
AB  - Background & objectives: It is imperative to know the aetiology of acute
      encephalitis syndrome (AES) for patient management and policy making. The present
      study was carried out to determine the prevalence of common aetiological agents
      of AES in Uttar Pradesh (UP) state of India. Methods: Serum and/or CSF samples
      were collected from AES patients admitted at Gandhi Memorial and Associated
      Hospital, King George's Medical University, Lucknow, a tertiary care centre, UP
      during 2014-16. Cerebrospinal fluid (CSF) and serum samples from cases were
      tested for IgM antibodies against Japanese encephalitis virus (anti-JEV), and
      dengue virus (anti-DENV) by ELISA; and for enterovirus, herpes simplex virus
      (HSV) and varicella zoster virus (VZV) by real-time PCR. Serum samples of cases
      having sufficient CSF volume, were also tested for anti-scrub typhus IgM
      antibodies and for Neisseria meningitides, Streptococcus pneumoniae and
      Haemophilus influenzae. Results: JEV and DENV (8% each) were the most common
      identified aetiology from the 4092 enrolled patients. Enterovirus, HSV and VZV,
      each were detected in <1% AES cases. Co-positivity occurred in 48 cases. Scrub
      typhus (31.8%) was the most common aetiology detected. Haemophilus influenzae and
      S. pneumoniae were detected in 0.97 and 0.94% cases, respectively, however, N.
      meningitides was not detected in any of the cases. About 40% of the JEV/DENV
      positive AES cases were adults. The gap between the total number of AES cases and
      those with JEV/ DENV infection increased during monsoon and post-monsoon seasons.
      Interpretation & conclusion: Scrub typhus, JEV and DENV are the main aetiological
      agents of AES in UP. DENV and JEV can no longer be considered paediatric
      diseases. The prevalence of non-JEV/DENV aetiology of AES increases in the
      monsoon and post-monsoon seasons.

PMID- 29460861
TI  - Immunogenicity of OmpA and OmpB antigens from Rickettsia rickettsii on
      mononuclear cells from Rickettsia positive Mexican patients.
AB  - Background & objectives: The nature of the rickettsial antigens and the immune
      response generated by them, have been the subject of exhaustive research so that
      a suitable vaccine can be developed. Till date evaluations of Rickettsia
      rickettsii antigens that induce both humoral and cellular responses in animal
      models have only shown partial protection and short-term immunological memory.
      This study was aimed to evaluate the immune response induced by DNA plasmids
      generated from the OmpA and OmpB genes of R. rickettsii in peripheral blood
      mononuclear cells of rickettsial (sensitized) patients compared to healthy
      subjects. Methods: Plasmids OmpA-49, OmpB-15 and OmpB-24 were generated in the
      pVAX vector. Macrophages derived from the THP-1 cell line were transfected in
      vitro with the plasmids and were co-cultured with T-lymphocytes from sensitized
      subjects and healthy subjects to evaluate cell proliferation and cytokine
      production. Results: The OmpB-24 plasmid induced proliferative response in human
      lymphocytes, with production of IL-2, IFN-gamma, IL-12p70, IL-6 and TNF-alpha,
      likely due to the presence of conserved epitopes among R. rickettsii, R. typhi
      and R. felis (differing from 1 to 3 amino acids) during the construction of the
      plasmids. Interpretation & conclusion: DNA sequences of rickettsial epitopes can
      be cloned into the pVAX vector. Constructed plasmids can generate a proliferative
      response and produce cytokines in vitro, in co-culture of transfected macrophages
      with sensitized human lymphocytes. Plasmid OmpB-24 proved to be the most
      immunogenic with respect to plasmids OmpA-49 and OmpB-15.

PMID- 29460862
TI  - Host preferences and feeding patterns of Anopheles sinensis Wiedemann in three
      sites of Shandong province, China.
AB  - Background & objectives: Anopheles sinensis Wiedemann is a major vector of
      malaria and is among the dominant species in Shandong province of China.
      Knowledge of the blood-feeding patterns of mosquitoes is crucial for elimination
      of malaria vectors. However, little information is available on the blood-feeding
      behaviour of An. sinensis mosquitoes in Shandong province. This study was carried
      out to compare the blood-feeding behaviour of An. sinensis in malaria-endemic
      areas of Shandong province China. Methods: Adult Anopheles mosquitoes were
      collected from three malaria-endemic areas (Jimo, Yinan and Shanxian), during the
      peak months of mosquito population (August and September) from 2014 to 2015.
      Indoor-resting mosquitoes and outdoor-resting blood-fed females were sampled in
      the morning hours (0600 to 0900 hrs) from 10 randomly selected houses using
      pyrethrum spray catch method, and sweeping with an insect net. ELISA was used for
      the identification of blood meal. The blood meal of each mosquito was tested
      against antisera specific to human, pig, dog, cow, goat, horse (mule) and fowl.
      Results: At all indoor study locations of Jimo, Yinan and Shanxian, 59.4, 68.1
      and 98.8% blood-engorged female An. sinensis collected from cattle sheds fed
      almost exclusively on bovines, respectively. For outdoor locations, at Jimo site,
      27.27 and 49.55% An. sinensis fed on cattle and pigs; at Yinan, 30.42% fed on
      cattle and 36.88% fed both on cattle and goats, while no pig antibodies were
      detected. At Shanxian, percent of An. sinensis that fed on cattle, pigs and
      cattle-goat was 20.72, 27.62 and 21.78%, respectively. Interpretation &
      conclusion: The analysis of An. sinensis blood meals in all the three studied
      areas from human houses, cattle sheds, pig sheds and mixed dwellings revealed
      that An. sinensis prefers cattle hosts, and can feed on other available animal
      hosts if the cattle hosts are absent, and the mosquitoes readily feed on humans
      when domestic animals (cattle and pigs) are not nearby for feeding. The analysis
      of blood meal revealed that An. sinensis follow opportunistic feeding in Shandong
      province, China.

PMID- 29460863
TI  - Entomological determinants of malaria transmission in an epidemic prone area of
      District Nuh (Haryana state), India.
AB  - Background & objectives: Entomological investigations were carried out in highly
      malarious villages under Ujina PHC of District Nuh (Haryana state) which is an
      epidemic prone area in northwestern region of India. The study was aimed to have
      an in-depth understanding of the entomological parameters influencing malaria
      transmission in the study area. Methods: The seasonal prevalence and biological
      attributes of vector mosquitoes were investigated during 2015 and 2016. Indoor
      resting vector mosquitoes were collected from human dwellings/cattle sheds and
      morphologically identified. Anopheles culicifacies were categorized to sibling
      species by species-specific inversions in polytene chromosomes and An. stephensi
      to ecological races on the basis of ridge number on egg float. The blood meal
      source analysis and incrimination studies of vectors were done by counter-current
      immunoelectrophoresis and enzyme-linked immunosorbent assay, respectively.
      Insecticide susceptibility test on vectors was performed as per WHO guidelines.
      Results: Seasonal abundance of An. culicifacies and An. stephensi in the study
      area showed variation; the peak densities of both the vectors were observed
      during monsoon months which correlated well with the average monthly rainfall
      data. Though both vectors were found to be primarily zoophagic, the human blood
      index of An. culicifacies (HBI = 0.17) was significantly higher than that of An.
      stephensi (HBI= 0.02). Analysis of sibling species composition of An.
      culicifacies population showed that it comprised almost of sibling species A
      (>98%) which is an established malaria vector. Anopheles culicifacies was
      incriminated for Plasmodium vivax and P. falciparum circumsporozoite (CS) antigen
      during monsoon months in 2015 and 2016. Assessment of insecticide susceptibility
      status of malaria vectors against 0.5% deltamethrin revealed that An.
      culicifacies is more susceptible (95% mortality) than An. stephensi (85%
      mortality). Interpretation & conclusion: The results suggest that An.
      culicifacies (species A) is playing a major role in malaria transmission in the
      study area and is almost susceptible to deltamethrin. Timely two rounds of indoor
      residual spray of synthetic pyrethroid with proper dosage and good coverage would
      be helpful in reducing vector population and consequently the malaria incidence.
      In addition, personal protection measures by the community would supplement the
      major intervention tool (IRS) in decreasing the man-vector contact.

PMID- 29460864
TI  - Serosurvey of Coxiella burnetii in high risk population in Turkey, endemic to
      Crimean-Congo haemorrhagic fever virus.
AB  - Background & objectives: Q fever caused by Coxiella burnetii is a zoonotic
      infection that spreads to human beings from animals. This study was aimed to
      demographically examine the C. burnetii seroprevalence in the people living in
      villages where Crimean-Congo haemorrhagic fever virus (CCHFV) is endemic, in
      terms of various risk factors such as tick bites, tick contact, and occupational
      groups. Methods: A total of 440 serum samples from those living in rural areas of
      Sivas and Tokat regions in Turkey were included in the study as a risk group;
      387of them were serologically CCHFV positive (as confirmed in our previous
      research). Serums of the control group composed of 110 people living in urban
      areas. In all serum samples, IgG antibodies of C. burnetii against phase-I and
      phase-II antigens were diagnosed using the ELISA method. Results: Coxiella
      burnetii seropositivity was detected in 19.09% of those living in rural areas and
      4.55% of those living in urban areas (p < 0.001, OR = 4.96). In terms of their
      approach to the ticks, no statistical difference was observed between the risk
      groups in the chi-square test (p = 0.787). However, according to univariate
      analysis, the absorbance means of antibodies reactive to C. burnetii was
      statistically higher for the rural people who have made contact with ticks than
      those who have not (p = 0.017). No seroepidemiological relation was found between
      CCHFV and C. burnetii serology (p = 0.787), and the rate of co-seropositivity
      between them was 5.43% (21/387). Interpretation & conclusion: The findings of the
      study showed that C. burnetii infection is epidemic especially in the people
      living in rural areas. Contact with ticks in various ways might have resulted in
      the increased risk of C. burnetii infection in the study. Personal protective
      measures against tick bites may be important for reducing Q fever risk as in
      other tick-borne infectious disease.

PMID- 29460865
TI  - The first positive serological study on rift valley fever in ruminants of Iran.
AB  - Background & objectives: Rift Valley fever (RVF) is a zoonotic vector-borne
      disease that primarily affects domestic animals but can also infect humans. The
      purpose of the present study was to investigate the presence of antibodies
      against RVF virus (RVFV) in ruminants, viz. cattle, sheep, and goats in Kurdistan
      Province of western Iran. Methods: Blood samples were collected from 288
      ruminants (118 cattle, 142 sheep and 28 goats) of both sexes, under age groups
      <=1, 1-3, 3-5 and >=5 yr, from January 2016 to December 2016. Clinical symptoms
      and history of abortion were recorded. The presence of RVFV-specific antibodies
      was investigated by using ELISA (competitive) and indirect immunofluorescence
      assay (IIFA) after separation of serum. Results: The results of two tests were
      positive for five (1.74%) of total 288 animals which included two cattle of 118
      (1.7%), and three sheep of 142 (2.11%). The results of IIFA were correlated with
      the ELISA results. All animals were clinically normal. No significant
      relationship between the RVFV infection rate and the variable considered, i.e.
      season, animal's age or sex, and the species of the animal (p >= 0.05), although
      there were four seropositive animals in the age group 1-3 and five seropositive
      animals in the spring season. Interpretation & conclusion: The results of the
      study revealed the presence of low-level RVFV circulation among the ruminants of
      Kurdistan Province in Iran indicating that they are at risk of exposure to the
      virus during their lifetime. Since the present study was the first serological
      study on RVF in Iran with positive results, further studies are suggested
      including other areas of Iran.

PMID- 29460866
TI  - Vector prevalence and detection of Crimean-Congo haemorrhagic fever virus in
      Golestan Province, Iran.
AB  - Background & objectives: Crimean-Congo haemorrhagic fever virus (CCHFV) causes
      severe disease with fatality rate of 30%. The virus is transmitted to humans
      through the bite of an infected tick, direct contact with the products of
      infected livestock as well as nosocomially. The disease occurs sporadically
      throughout many of African, Asian and European countries. Different species of
      ticks serve either as vector or reservoir for CCHFV. This study was aimed to
      determine the prevalence of CCHFV in hard ticks (Ixodidae) in the Golestan
      Province of Iran. Methods: A molecular survey was conducted on hard ticks
      (Ixodidae) isolated from six counties in Golestan Province, north of Iran during
      2014-15. The ticks were identified using morphological characteristics and
      presence of CCHFV RNA was detected using RT-PCR. Results: Data revealed the
      presence of CCHFV in 5.3% of the ticks selected for screening. The infected ticks
      belonged to Hyalomma dromedarii, Hy. anatolicum, Hy. marginatum and Rhipicephalus
      sanguineus species. Interpretation & conclusion: The study demonstrated that
      Hyalomma ticks are the main vectors of CCHFV in Golestan Province. Thus,
      preventive strategies such as using acaricides and repellents in order to avoid
      contact with Hyalomma ticks are proposed.

PMID- 29460868
TI  - Functional response and density dependent feeding interaction of Oreochromis
      niloticus against immatures of Culex quinquefasciatus.

PMID- 29460867
TI  - Leishmaniasis in northern Cyprus: Human cases and their association with risk
      factors.
AB  - Background & objectives: Cyprus is located in the eastern part of the
      Mediterranean Region where leishmaniasis is endemic. The primary objective of
      this study was to investigate human visceral leishmaniasis (VL) in the northern
      region of Cyprus where presence of canine leishmaniasis (CanL) and sandflies has
      been documented in earlier studies. The secondary objective was to assess the
      association of leishmaniasis with demographic and epidemiological variables.
      Methods: Intravenous blood samples were collected from 249 volunteers in Kyrenia
      district (located in the northern coastal region of Cyprus). Whole blood samples
      were tested for DNA of Leishmania spp by polymerase chain reaction (PCR), while
      serum samples were analyzed using direct agglutination test (DAT) and rK39 test.
      For evaluation of possible risk factors, a questionnaire was applied to the
      participants. Results: Only three (1.2%) of 249 participants were found
      seropositive by DAT (n = 2) or rK39 test (n = 1). The remaining samples were
      negative in serology, and no PCR positivity was detected in any of the 249
      participants. Seven individuals, including the seropositive cases, had a history
      of cutaneous leishmaniasis (CL). Seropositivity and CL were not significantly
      related with gender (M/F: 40.2/59.8%), age [Mean: 42.85 +/- 17.45, Median: 40 (7
      86)], occupation (Indoor/Outdoor: 84.7/12.9%), dog ownership (52.6%), and CanL
      history (5.3%). However, a statistical association was found between
      seropositivity and past CL infection. Also, a significant relation was observed
      between participants living in peripheral area (63.1%) and CL infection.
      Furthermore, leishmaniasis awareness (28.1%) among the study population was
      statistically correlated with past CL infection and dog ownership. Interpretation
      & conclusion: This study demonstrates the presence of leishmaniasis and highlight
      the need for implementation of efficient control measures on the northern coast
      of Cyprus.

PMID- 29460869
TI  - Scrub typhus in Mizoram, India.

PMID- 29460870
TI  - Malaria and the heart: Two rare case reports of Plasmodium falciparumassociated
      pericarditis.

PMID- 29460872
TI  - Author's reply.

PMID- 29460871
TI  - Epidemiological and demographic characteristics of dengue at a tertiary care
      centre in Gujarat.

PMID- 29460873
TI  - Thoracoscope-Assisted Mitral Valve Replacement with a Small Incision in the Right
      Chest: A Chinese Single Cardiac Center Experience.
AB  - BACKGROUND The aim of this study was to investigate the safety, feasibility, and
      clinical effectiveness of thoracoscopy-assisted mitral valve replacement via
      thoracic right-anterior minimal incision. MATERIAL AND METHODS A retrospective
      analysis was conducted of 225 patients with mitral valve lesions who were treated
      in our hospital from August 2012 to August 2015. Group A included 105 patients
      undergoing thoracoscopy-assisted mitral valve replacement via a thoracic right
      anterior minimal incision, and group B included 120 patients undergoing
      conventional mitral valve replacement. We collected and analyzed clinical data
      from both groups. RESULTS The procedures were successful in patients of both
      groups. No severe complications or mortality were reported. Postoperative
      mechanical ventilation time (8.6+/-2.4 h vs. 12.4+/-3.2 h), duration of intensive
      care (1.7+/-1.2 d vs. 2.8+/-1.3 d), duration of postoperative analgesia use
      (28.7+/-8.9 h vs. 36.3+/-7.5 h), postoperative length of hospital stay (8.2+/-2.2
      d vs. 12.8+/-2.1 d), pleural fluid drainage (210.5+/-60.5 ml vs. 425.4+/-75.6
      ml), blood transfusion amount (420.5+/-80.4 ml vs. 658.3+/-96.7 ml), and
      operative incision length (4.7+/-1.1 cm vs. 22.4+/-2.5 cm) were significantly
      shorter (or lower) in group A than in group B. There were different advantages
      and disadvantages in the 2 kinds of operative procedure in terms of postoperative
      complications. CONCLUSIONS Thoracoscopy-assisted mitral valve replacement via
      thoracic right-anterior minimal incision has the same clinical efficacy, safety,
      and feasibility as conventional mitral valve replacement.

PMID- 29460874
TI  - [Robot-assisted atrial septal defect closure in adults: first experience in
      Russia].
AB  - AIM: To analyze immediate results of minimally invasive robot-assisted atrial
      septal defect (ASD) closure in adults. MATERIAL AND METHODS: For the period from
      March 2012 to November 2016 sixty patients with contraindications to endovascular
      procedure have undergone robot-assisted atrial septal defect closure at Meshalkin
      Siberian Federal Biomedical Research Center. Mean age was 34.5+/-11.3 years, body
      mass index - 24.6+/-4.0 kg/m2. 48 (80%) patients had NYHA class II before
      surgery. In 37 (61.7%) patients isolated ASD with deficiency or absence of one
      edge was diagnosed, isolated ASD with primary septum aneurysm - in 16 (26.7%)
      cases, 7 (11.6%) patients had reticulate ASD. 5 (8.3%) patients had concomitant
      tricuspid valve insufficiency required surgical repair (suture annuloplasty). All
      operations were performed under cardiopulmonary bypass with peripheral
      cannulation. Right-sided anterolateral mini-thoracotomy was used in the first 43
      patients. Following 17 patients underwent completely endoscopic procedure.
      Depending on the shape, size and anatomical features of the defect we performed
      suturing (14 patients, 23.3%) or repair with xenopericardial patch (46%, 76.6%).
      RESULTS: Mean CPB and aortic cross-clamping time was 89.1+/-28.7 and 24.8+/-9.5
      min, respectively. Postoperative variables: mechanical ventilation 3.3+/-1.5
      hours, ICU-stay - 18.2+/-3.7 hours, postoperative hospital-stay - 13.4+/-5.7
      days. There were no mortality and any life-threatening intra- and postoperative
      complications. Cases of conversion to thoraco-/sternotomy and postoperative
      bleeding followed by redo surgery were also absent. 23 patients were followed-up
      within 1 year, 6 patients - within 2 years, 3 patients - within 3 years. All
      patients were in NYHA class I-II with 100% freedom from ASD recanalization and
      redo surgery. According to echocardiography data there were decreased right
      heart, pulmonary artery pressure and preserved left ventricular function in early
      postoperative period and 1 year after surgery. CONCLUSION: In view of favorable
      course of postoperative period, no significant specific complications and
      encouraging immediate results we can talk about endoscopic robot-assisted ASD
      closure in adults as a safe and effective alternative to surgical treatment.

PMID- 29460876
TI  - [Thoracoscopic repair of postoperative intrapleural complications].
AB  - AIM: To justify and develop the indications for thoracoscopic procedures in
      patients with complications after advanced cardiothoracic surgery including
      combined and simultaneous operations. MATERIAL AND METHODS: From 2013 to 2017 was
      performed treatment of complication in 27 patients undergoing various
      cardiothoracic intervention with the use of thoracoscopic technology. RESULTS: We
      have analyzed immediate results of thoracoscopic operations in 27 patients with
      various intrapleural complications after advanced cardiothoracic surgery.
      Satisfactory results of these interventions confirm safety of thoracoscopic
      technologies and serve as an argument in favor of this direction in thoracic
      surgery.

PMID- 29460875
TI  - [Staged approach for hybrid thoracoabdominal aortic replacement].
AB  - AIM: To generalize our experience of step-by-step hybrid thoracoabdominal aortic
      replacement. MATERIAL AND METHODS: Twenty-three patients were enrolled who
      underwent staged hybrid treatment of thoracoabdominal aortic aneurysm. There were
      5 (21.7%) women and 18 (78.3%) men aged 61.4+/-8.3 years (37-74 years). The first
      stage was proximal debranching, the second - distal (abdominal) procedure and the
      third - stenting of the thoracoabdominal aorta. RESULTS: There were no any
      complications after proximal debranching and aortic stenting. Abdominal
      debranching was followed by lethal outcome in 3 (13.0%) patients and early
      postoperative occlusion of the prosthesis brunch in 3 out of 87 cases.
      CONCLUSION: Staged approach for hybrid surgical treatment is optimal solution,
      especially in high risk patients. In our opinion no necessity for cardiopulmonary
      bypass is the main advantage of this technique.

PMID- 29460877
TI  - [Associated Liver Partition and Portal vein ligation for Staged hepatectomy
      (ALPPS) in focal liver diseases management].
AB  - AIM: To determine ALPPS advisability in small future remnant liver. MATERIAL AND
      METHODS: 22 ALPPS procedures were performed at the Center for Surgery and
      Transplantology for the period from 2011 to 2016. Indications were both tumoral
      and non-tumoral unresectable liver diseases. Postoperative complications were
      classified according to Clavien-Dindo, ISGLS. RESULTS: According to CT-volumetry
      future remnant liver before the 1st stage of ALPPS was from 17 to 25%, before the
      2nd stage - from 28 to 49%. Both stages were carried out in all patients with R0
      resection in 100%. Postoperative complications were diagnosed in 40.9%, 1 death
      was caused by severe pulmonary embolism. Follow-up varied from 3 to 48 months
      (median 17.5), 86% of patients are alive at present. CONCLUSION: ALPPS provides
      rapid and effective FLR growth and can be used for both tumoral and non-tumoral
      unresectable liver diseases. However, ALPPS should be performed strictly
      according to indications and only in specialized centers with extensive
      experience of advanced liver resection and transplantation after previous
      comprehensive selection of patients.

PMID- 29460878
TI  - [Laparoscopic pancreatic head resection].
AB  - AIM: To analyze the features and efficacy of laparoscopic Frey procedure.
      MATERIAL AND METHODS: For the period from August 2012 to May 2017 Frey procedure
      was carried out in 31 patients with chronic calculous pancreatitis Buchler type
      C. There were 20 men and 11 women aged 48.6+/-9 years. Mean pancreatic head
      dimension was 35.5+/-14 mm, diameter of the main pancreatic duct - 9.6+/-2.7 mm.
      RESULTS: Completely laparoscopic procedure was made in 28 (90.3%) cases. One
      patient required intraoperatively Beger's technique without conversion. The last
      was need in 2 (6.5%) cases. Time of surgery and blood loss were 447.3+/-90.4 min
      and 215+/-177.7 ml respectively. Mean postoperative hospital-stay was 8.4+/-4.5
      days. Postoperative complications occurred in 7 patients. Mortality was absent.
      Follow-up was 1-41 months. Recurrent pain syndrome was observed in 1 case.
      However, it was less severe and does not require analgesia.

PMID- 29460879
TI  - [Non-functioning gallbladder as a risk factor for bile ducts injury during
      laparoscopic cholecystectomy].
AB  - AIM: To analyze the effect of gallbladder's morpho-functional changes as a risk
      factor for injury of extrahepatic bile ducts during cholecystectomy. MATERIAL AND
      METHODS: Laparoscopic cholecystectomy was performed in 20 564 patients. There
      were 147 64 (71.8%) patients with chronic gallbladder inflammation and 5800
      (28.2%) - with acute process. It was performed a retrospective analysis of the
      incidence and causes of intraoperative trauma of extrahepatic bile ducts and bile
      outflow. Two groups of comparison were distinguished: acute calculous
      cholecystitis and chronic inflammation. RESULTS: There were 93 (0.04%)
      complications followed by bile outflow (55 (0.94%) in the 1st group and 38
      (0.25%) in the 2nd group). Marginal injury of the ducts was interoperatively
      detected in 5 patients of group 1 and 3 patients of 2 groups. In postoperative
      period it was found in 6 patients of the 1st group due to electric trauma of
      common bile duct. Complete transection of common bile duct occurred in 10 (8.8%)
      cases, while chronic calculous cholecystitis was observed in 8 of them. At the
      same time, in 6 patients these were surgical interventions in scleroatrophic
      gallbladder. As a results, we determined the forms of non-functioning gallbladder
      with morphofunctional changes which promote trauma of extrahepatic bile ducts.
      CONCLUSION: Long-term non-functioning gallbladder leads to cicatricial and
      adhesive processes in its wall and surrounding tissues that significantly
      complicates cholecystectomy and increases the risk of bile ducts trauma.
      Scleroatrophic gallbladder is the most dangerous which occurs in 4.1% of patients
      with chronic calculous cholecystitis. Further trials are advisable to develop
      optimal therapeutic and diagnostic tactics for various forms of long-term non
      functioning gallbladder.

PMID- 29460880
TI  - [Outcomes of cardiac achalasia grade II-III management].
AB  - AIM: To analyze early and remote results of the new method of cardiac achalasia
      grade II-III management. MATERIAL AND METHODS: Original surgical approach was
      applied in 21 patients with cardiac achalasia grade II-III. RESULTS: There were
      no any specific postoperative complications and deaths. Exacerbation of chronic
      pancreatitis, acute stomach ulcer and biliary peritonitis were observed in 3
      cases respectively. All patients were followed-up within the period from 1.5
      months to 5 years after surgery. Recurrent disease was absent. All employable
      patients have backed to work. CONCLUSION: According to clinical and instrumental
      data original surgical repair completely cures the symptoms of cardiac achalasia
      and restores normal esophageal dimensions and structure early after intervention.

PMID- 29460881
TI  - [Vacuum-assisted excision of focal dysplasia of mammary glands. Single-center
      experience].
AB  - AIM: To assess the diagnostic significance and safety of vacuum-assisted
      resection in patients with focal breast cancer BIRADS category 3 and 4. MATERIAL
      AND METHODS: The procedure was performed in 50 women aged 22 to 51 years (35.1+/
      2.6 years). RESULTS: There were no any complications immediately after vacuum
      resection. Tissue of the neoplasm was removed in full in all patients. Benign and
      malignant tumors were observed in 94 and 6% cases respectively. All cases were
      identified in BIRADS category 3. CONCLUSION: Vacuum-aspiration resection is of
      great importance in the diagnosis and treatment of focal dysplasia of the mammary
      glands. It has a high diagnostic accuracy, allows you to remove focal disease in
      full without serious complications.

PMID- 29460882
TI  - [Results of video-assisted technologies in colorectal surgery].
AB  - AIM: To analyze immediate outcomes of 286 laparoscopic and robot-assisted
      interventions on the colon and rectum. MATERIAL AND METHODS: There were 256
      (89.51%) laparoscopic and 30 (10.49%) robot-assisted procedures. 233 (81.46%)
      operations were performed for rectum and colon cancer. Postoperative
      complications after colon cancer surgery were revealed in 11.11%, including
      anastomosis failure in 2.08% of cases. Postoperative complications after rectal
      cancer surgery occurred in 32.58% of cases including anastomosis failure after
      anterior rectectomy in 11.67%. CONCLUSION: Robot-assisted surgery is not
      advisable for colon diseases according to price-effectiveness ratio due to
      available laparoscopic approach. Preventive intestinal stoma in endoscopic low
      and ultra-low anterior rectal resection allows you to avoid clinically
      significant inconsistency of colorectal anastomosis. Laparoscopic procedure
      should be performed with Contour stitching-cutting device in low and ultra-low
      anterior rectal resection if there is technical complexity of one-stage rectum
      intersection below the tumor. Robot-assisted operations for rectal cancer have
      advantages due to three-dimensional imaging and better orientation, greater
      freedom of manipulation in confined spaces, and simplicity of lymphadenectomy.

PMID- 29460883
TI  - [Efficacy of video-assisted procedures in advanced age patients with colorectal
      cancer].
AB  - AIM: To assess advisability of video-assisted surgery in advanced age patients
      with colorectal cancer. MATERIAL AND METHODS: The study involved 44 patients with
      large intestine tumors. There were 30 patients with colon cancer aged 78.0+/-1.1
      years and 14 patients with rectal neoplasms aged 75.0+/-1.8 years. All of them
      underwent elective video-assisted resections without conversion of the approach.
      RESULTS: Good and satisfactory results were achieved in 95.5% of patients.
      Postoperative complications occurred in 5 (11.4%) cases followed by redo surgery
      in 2 (4.5%) patients. Mortality was absent. CONCLUSION: Video-assisted procedures
      are preferable in elective surgery of colorectal cancer in advanced age patients
      regardless stage and localization of the process.

PMID- 29460884
TI  - [A new approach in the compression therapy of postoperative scars].
AB  - : The aim of the study was to evaluate the effectiveness of compression therapy
      with a prolonged plaster of Contractubex in the formation of skin scarring in
      children after surgery. MATERIAL AND METHODS: In a prospective open-label
      randomized trial, 109 patients aged 5.3+/-2.1 years after surgery: boys - 73,
      girls - 36. Patients were divided into 2 groups: in the main group (54 children)
      the application of the prolonged plaster Contractubex was performed; in the
      control group (55 patients) - dynamic observation. The scar deformation was
      assessed according to the Vancouver scale for 10, 30 and 90 postoperative days.
      RESULTS: 94.4% patients had good compliance; in 2 (3.7%) - satisfactory; in 1
      (1.9%) - unsatisfactory compliance. In our study, the formation of hypertrophic
      scars in the main group was significantly less frequent than in the control group
      (1 and 8 patients, respectively, chi2=4.241, p=0.042). CONCLUSION: Thus, the use
      of the prolonged plaster Contractubex in the near and distant period a good
      cosmetic and functional result in the formation of a postoperative scar was
      provided.

PMID- 29460885
TI  - [Percutaneous drainage of liver abscess in case of situs viscerus inversus].

PMID- 29460886
TI  - [Conventional and eversion carotid endarterectomy for internal carotid artery
      stenosis].

PMID- 29460887
TI  - [Risk stratification in carotid artery stenting].

PMID- 29460888
TI  - [Is medication possible for acute appendicitis?]
AB  - AIM: To study the possibility of antibacterial therapy for acute appendicitis as
      an alternative to surgical treatment. MATERIAL AND METHODS: For the period 1985
      2010 diagnostic laparoscopy was performed in 5548 patients with suspected acute
      appendicitis. Acute phlegmonous or gangrenous appendicitis was observed in 2275
      (41.0%) patients who underwent laparoscopic appendectomy. Other acute diseases
      occurred in 2458 (44.3%) patients. Acute catarrhal appendicitis or secondary
      inflammation of the appendix were diagnosed in 815 (14.7%) patients; they did not
      get appendectomy. In-hospital antibacterial therapy has been administered for 1-2
      days followed by discharge for outpatient treatment. One patient with acute
      destructive appendicitis who refused surgery was treated with antibiotics.
      RESULTS: Antibacterial therapy in 815 patients with acute catarrhal appendicitis
      allowed to avoid surgical treatment. Complications (appendicular infiltration,
      abscess), repeated hospitalizations within 1 month were absent. Antibacterial
      treatment provided recovery in 1 patient with destructive appendicitis who
      refused surgical treatment. CONCLUSION: Patients with acute catarrhal
      appendicitis diagnosed with laparoscopy do not need for appendectomy and can be
      cured by antibacterial therapy.

PMID- 29460889
TI  - [Cerebral infarctions in vertebrobasilar artery atherosclerosis].
AB  - AIM: to obtain more specific information on the morphology and pathogenesis of
      cerebral infarctions occurring in vertebrobasilar artery (VBA) atherosclerosis.
      MATERIAL AND METHODS: Macro- and microscopic investigations of the brain, its
      arterial system, and heart were conducted in 69 autopsy cases with infarctions
      located in the vertebrobasilar system (VBS) in atherosclerosis. RESULTS: 69 cases
      were found to have 206 VBA infarctions of various extent and locations. The
      detected infarctions were single and multiple in 27 and 42 cases, respectively.
      The detected infarctions included extensive (n=7), large (n=9), medium (n=63),
      small deep (lacunar) (n=97), and small superficial (n=30). The brain stem showed
      lacunar infarctions most frequently (76% of the infarctions at this site). Medium
      and small infarctions were identified at the same frequency in the cerebral
      hemispheres and cerebellum. The occurrence of 94% of the extensive and large
      infarctions was ascertained to be pathogenetically associated with
      atherothrombotic occlusion of the intracranial arteries in the VBS. 76% of the
      small infarctions occurred through the mechanism of cerebral vascular
      insufficiency in tandem atherostenosis of VBAs in conjunction with an additional
      decrease in cerebral blood flow under the influence of an extracerebral factor
      (coronary heart disease). Medium infarctions were approximately equifrequently
      due to the two aforementioned causes and, in some cases, to cardiogenic
      thromboembolism of VBAs. Infarctions were multiple in most cases; while recent
      large atherothrombotic infarctions were frequently concurrent with small
      organized infarctions resulting from tandem atherostenosis of VBAs. CONCLUSION:
      This investigation could establish the relationship between the site, extent, and
      pathogenetic factors of infarctions in the VBA bed in atherosclerosis, as well as
      the prognostic value of small infarctions as predictors for severe ischemic
      stroke.

PMID- 29460890
TI  - [Increased myocardial expression of Toll-like receptors 2 and 9 as a marker of
      active myocarditis and a possible predictor of therapeutic effectiveness].
AB  - AIM: to investigate the myocardial expression of some structural proteins and
      markers of cellular proliferation and innate immunity for assessing their
      possible diagnostic and prognostic role in patients with chronic myocarditis.
      SUBJECTS AND METHODS: The investigation enrolled 23 patients (16 men; mean age,
      52.0+/-12.4 years (range, 27 to 73) with various forms of noncoronarogenic
      myocardial injury who underwent right ventricular endomyocardial biopsy (n=4),
      intraoperative left ventricular biopsy (n=17) or autopsy (n=2). Prior to their
      morphological examination, the patients were divided into two groups: 1) 10
      patients with dilated cardiomyopathy and presumptive myocarditis; 2) 13 patients
      with valvular heart disease, hypertrophic cardiomyopathy, myxoma, and chronic
      pulmonary thromboembolism, presumptively without myocarditis. Along with
      myocardial histological and immunohistochemical (IHC) examinations, the
      expression of vimentin, desmin, c-kit, Ki-67, and Toll-like receptors (TLR) 2 and
      9 was determined. Polymerase chain reaction was used to identify whether herpes
      viruses of and parvovirus B19 genomes were present in the blood and myocardial
      samples; indirect ELISA was applied to estimate the blood level of antibodies
      against various cardiac antigens. RESULTS: According to the histological
      findings, active/borderline lymphocytic myocarditis was diagnosed in all the
      patients (Group 1) and in 6 patients (Group 2) in conjunction with the underlying
      disease (only in 9 and 7 patients, respectively), viral genome was detected in
      the myocardium of 15 patients, including in 5 without morphological signs of
      myocarditis (parvovirus B19 (n=11), herpesvirus 6 (n=4), herpes simplex virus
      types 1 and 2 (n=1), Epstein-Barr virus (n=2), and cytomegalovirus (n=1)), and in
      the blood (n=4). A marked correlation was found between TLR2 and TLR9 expressions
      and the morphological pattern of active myocarditis in the absence of this
      correlation with the expression level of other studied markers. The expression
      level of TLR2 in patients with and without borderline myocarditis was 0 [0; 0,75]
      and in those with active myocarditis was 1.5 [1; 1,5] points; that of TLR9 was 2
      [2; 2] and 4 [3; 4] points, respectively (p<0.001). The expression of TLR2 and
      TLR9 in patients with borderline myocarditis was lower than in those without
      myocarditis (0 [0; 0] versus 0 [0; 1] and 2 [1,5; 2] versus 2 [2; 3] points),
      which can reflect cardiomyocyte destruction/depletion at later stages of the
      disease. There was also a close correlation between the expression level of TLR2
      and that of TLR9 (r=0.824; p<0.001) and with Ki-67 levels (r=-0.531 and r=-0.702;
      p<0.01). There was also a correlation of the expression of the studied markers
      with viral persistence (desmin), the degree of myocardial dysfunction and
      cardiosclerosis (c-kit), which calls for further investigations. CONCLUSION:
      Determination of the myocardial expression level of TLR2 and TLR9 may serve as an
      immunohistochemical marker for myocarditis and preservation of its activity,
      which is especially valuable in patients with borderline forms. The marked
      expression of these markers for innate immunity may reflect both one of the
      mechanisms of genetic predisposition to myocarditis and its severe course and
      their secondary activation in the pathogenesis of the disease and is a potential
      target of therapy.

PMID- 29460891
TI  - [The proliferative activity of tumor cells and the distribution of SOX2+
      pluripotent stem cells in various histological types of ameloblastoma].
AB  - AIM: to investigate the proliferative activity and distribution of pluripotent
      stem cells in various histological types of amelobrastoma. MATERIAL AND METHODS:
      The surgical and archival materials of 76 patients with ameloblastoma from the
      Central Research Institute of Dentistry and Oral Surgery, Ministry of Health of
      the Russian Federation, were used. Tissue antigens were determined using a rabbit
      monoclonal antibody against to Ki-67 and SOX2. RESULTS: Proliferating (Ki-67) and
      pluripotent (SOX2) cells were identified in various histological types of
      ameloblastoma. A weak significant correlation was found between tumor size,
      pluripotent stem cells, and cellular proliferative activity. Enhanced cell
      proliferative activity and extensive bone tissue destruction significantly
      correlated with the development of recurrent ameloblastoma. CONCLUSION: The
      presence of pluripotent stem cells, the proliferative activity of ameloblastoma
      cells, and the extensiveness of bone tissue destruction allow basal-cell and
      plexiform options to be considered as the most aggressive indicators.

PMID- 29460892
TI  - [Coexpression of CD44 and Ki-67 in colon's neoplast].
AB  - AIM: the evaluation of Ki-67 and CD44 expression in the 'serrated' polyps of the
      colon and comparison them with adenocarcinomas and tubular and tubule-villous
      adenomas of the colon. MATERIAL AND METHODS: The study is including 49 'serrated'
      polyps, 34 tubular (AT) and tubulo-villous (ATV) adenomas and 32 adenocarcinomas
      of the colon. Antibodies CD44 and Ki-67 were used as immunohistochemical markers
      in this study. RESULTS: A statistically significant difference (p<0.01) was
      observed between traditional serrated adenomas (TSA) from hyperplastic polyps
      (HP) and sessile serrated adenomas (SSA) in the Ki-67 level and the localization
      of the Ki-67 and CD44 reaction: surface areas of the crypts (upper third) in TSA
      and base of crypts (lower third) in HP and SSA. There was no difference between
      HP and SSA (p>0.05), neither by marker localization, nor by their level. In all
      'serrated' polyps of the colon, the Ki-67 reaction was nuclear; CD44 - membrane
      (except for 1 TSA). CONCLUSION: we are the first ones who suggested to evaluate
      not the overall level of reactions of CD44 and Ki-67, but particular level for
      each third part of crypts. The similarities of TSA, AT and ATV and between HP and
      SSA are shown as well as the principal statistical difference between these two
      groups. The cytoplasmic reaction of CD44 in adenocarcinomas and the membrane
      reaction of CD44 in 98% of the 'serrated' polyps of the colon are described. For
      the first time coexpression of CD44 and Ki-67 on particulate thirds of crypts in
      neoplasms of the colon is shown and the potential reasons for this phenomenon are
      discussed.

PMID- 29460893
TI  - [The new international histological classification of thyroid tumors].
AB  - The International Agency for Research on Cancer (IARC) published the new 4th
      Edition of the WHO Classification of Tumors of Endocrine Organs in 2017. As the
      previous 2004 edition, the new classification gives considerable attention to
      thyroid neoplasms. The nomenclature of thyroid tumors undergone changes based on
      the clinical, morphological and molecular genetic findings obtained for the
      expired period, on respective new views of their malignant potential, and on the
      prognosis of a number of neoplasms that should be taken into consideration by
      pathologists in their daily diagnostic practice. The aim of this paper is to
      present the new Edition of Classification of Thyroid Tumors with an emphasis on
      the changes made.

PMID- 29460894
TI  - [The clinical and morphological characteristics of C1q glomerulopathy].
AB  - C1q glomerulopathy is a rare variety of chronic glomerulonephritis manifested as
      C1q deposition revealed by immunofluorescence microscopy. The pathogenesis and
      etiology of the disease have not been studied. The paper deals with the results
      of clinical, morphological, immunofluorescence, and electron microscopic
      examinations in 13 patients with C1q glomerulopathy. Light microscopy more
      commonly revealed membranous nephropathy, mesangioproliferative
      glomerulonephritis, and nephrosclerosis. Immunofluorescence microscopy detected a
      C1q fraction in association with other deposits, more frequently IgM and IgG
      ones. A correlation was found between the clinical presentation and morphological
      form of chronic glomerulonephritis.

PMID- 29460895
TI  - [On the histo- and morphogenesis of sclerosing pneumocytoma and its diagnostic
      criteria].
AB  - The paper presents the data available in the literature on the pathogenesis,
      clinical and morphological, histological and immunohistochemical features of
      pulmonary sclerosing pneumocytoma (SP). The paper gives the detailed histological
      and immunohistochemical characteristics of 6 SP cases. The need for the
      differential diagnosis of SP is determined by the features and complexity of
      their histo- and morphogenesis within a single tumor and a complex diagnostic
      study.

PMID- 29460896
TI  - [Renal cell carcinoma associated with Xp11 translocation involving the gene].
AB  - The paper describes a clinical case of the rare tumor renal cell carcinoma
      associated with Xp11 translocations involving the TFE3 gene in a 53-year-old male
      patient. It provides the detailed characteristics of current diagnostic
      techniques.

PMID- 29460897
TI  - [Is scleromyxedema a skin problem or systemic pathological process?]
AB  - Scleromyxedema is regarded as a rare cutaneous mucinosis from a group of lichen
      myxedematosus characterized by diffuse mucin deposition, sclerosis, and lichenoid
      eruptions in the absence of thyroid disease. The paper discusses the pathogenesis
      of the disease and histological changes in tissues. It underlines the need for
      using histochemical tests to identify acidic and neutral glycosaminoglycans and
      gives a differential diagnosis of this disease.

PMID- 29460898
TI  - [Social adaptation of patients with organic mental disorders in childhood: the
      results of the long-term study].
AB  - AIM: To analyze the clinical and social outcomes of organic mental disorders
      (OMD), diagnosed in children and teens; establish the factors that are relevant
      for the formation of the clinical picture of OMD in different sexes; the
      circumstances that determine the dynamics of remote OMD and the level of social
      adaptation of patients in adulthood. MATERIAL AND METHODS: Four hundred and
      ninety-eight children with organic mental disorders were followed-up in one of
      neuropsychiatric outpatient clinics of Moscow, until they reached 23-25 years of
      age. The total duration of observation was from 7.5 to 22 years (M+/-sigma:
      17.3+/-3.5 years). Clinical-psychopathological and follow-up methods were used.
      To assess social functioning of patients, a form for recording social skills of
      adolescents and a questionnaire for assessment of social functioning and quality
      of life were used. RESULTS AND CONCLUSION: In 82% of patients, OMD reduced by the
      time of adulthood. Disorders with severe intellectual impairment, paroxysmal
      disorders, psychopathic syndrome, mixed forms of the disease were the causes of a
      lifelong disability in 3.6% of cases.

PMID- 29460899
TI  - [The diagnostic significance of vestibular evoked myogenic potentials in
      different types of vertigo].
AB  - AIM: To study the parameters of vestibular evoked myogenic potentials (VEMPs) in
      different types of vertigo. MATERIAL AND METHODS: Seventy-seven patients, 35 men
      and 42 women, aged 43.7+/-12.5 years, with vestibular vertigo and unsteadiness
      were examined. The activity of the stemocleidomastoid muscle in response to
      auditory stimulation of the ipsilateral ear was recorded using surface
      electromyography. RESULTS: There were a trend towards the increase in the N2
      latency, the significant reduction of the P1-N2 amplitude (p<0,005) on both sides
      and significant changes in the coefficient of asymmetry. Compared to healthy
      people, the P1 latency and asymmetry in P1 latency were significantly increased
      in patients with peripheral type of vertigo (p<0,005 and r=0,0007, respectively).
      There were no differences in the P1 latency and N2 in patients with unsteadiness.
      CONCLUSION: In patients with peripheral vertigo, central vertigo and
      unsteadiness, vestibular-spinal reflex was disturbed at different levels of
      vestibular analyzer.

PMID- 29460900
TI  - [The study of the membrane-protective potential of the combination of 2-ethyl-6
      methyl-3-hydroxypyridine-succinate and citicoline].
AB  - AIM: To assess the changes in the composition of plasma phospholipids in patients
      with chronic cerebrovascular disease treated with neuroprotectors 2-ethyl-6
      methyl-3-hydroxypyridine succinate (neurox) and citicoline (neipilept), the
      natural metabolites involved in biochemical processes in the body, and their
      composition. MATERIAL AND METHODS: The study included 40 patients, 18 men and 22
      women, aged from 54 to 72 years, with chronic cerebrovascular disease at the
      decompensation stage complicated with the hypertensive crisis and/or arrhythmia.
      RESULTS AND CONCLUSION: During extraction of phospholipids from blood cells, a
      significant decrease in the amount of total lipids was found to the end of
      treatment of patients who received neurox or neipilept or their combination. The
      study of quantitative composition of phospholipids showed no significant changes
      in patients treated with neurox, while the use of citicoline or combination of
      citicoline with 2-ethyl-6-methyl-3-hydroxypyridine succinate resulted in the
      increase of their total mass. There were no significant changes in the
      qualitative composition of phospholipid classes in blood plasma in patients
      treated with neurox. In patients treated with neipilept or with the combination
      of citicoline with 2-ethyl-6-methyl-3-hydroxypyridine succinate, plasma
      phosphatidylcholine was significantly increased. No significant changes in the
      content of phosphatidylinositol, phosphatidylserine and sphingomyelin were
      observed.

PMID- 29460901
TI  - [The clinical significance of the lamotrigine pharmacokinetic variability].
AB  - AIM: To estimate pharmacokinetic variability of lamotrigine (LTG) and its
      clinical significance. MATERIAL AND METHODS: One hundred patients, including 74
      women, aged from 18 to 77 years (38.23+/-14.37 years), with focal epilepsy were
      examined. Monotherapy with LTG was administered to 54 patients, duotherapy to 46
      patients (LTG and valproic acid combination to 27 patients, LTG and liver enzymes
      inducers to 19 patients). Patients underwent procedures of therapeutic drug
      monitoring (TDM). Minimal (Cssmin) and maximal (Cssmax) steady-state LTG plasma
      concentrations, and concentration-to-weight ratio (CDR) were calculated. RESULTS
      AND CONCLUSION: In patients who used LTG in monotherapy, LTG Cssmin was 5.6+/
      4.65 mg/l, Cssmax 7.59+/-5.54 mg/l. In the group that received LTG in combination
      with valproate, LTG Sssmin was 7.8 [5.4; 11.8] mg / l and Cssmax 11.4 [7.3; 15.3]
      mg/l. In the group that received LTG in combination with drug-inducers of
      glucuronidation, Cssmin was 2.5 [1.99; 4.32] mg/l, Cssmax 4.73 [2.91; 6.70] mg/l.
      Statistically significant differences in CDR parameter between groups with LTG
      monotherapy and duotherapy, both with inducer and with inhibitors, as well as
      between groups of duotherapy with inductors and with inhibitors were obtained.
      The results of the study indicate a pronounced pharmacokinetic variability of the
      LTG. Conducting TDM allows the establishment of individual therapeutic
      concentrations of LTG in blood plasma and setting a correction vector for
      antiepileptic therapy.

PMID- 29460902
TI  - [The efficacy of cortexin and memantinol (memantine) in the treatment of
      cognitive impairment in patients with chronic cerebral ischemia].
AB  - AIM: To study the dynamics of cognitive impairment in patients with chronic
      cerebral ischemia (CCI) treated with cortexin and memantinol (memantine).
      MATERIAL AND METHODS: The authors present the results of the multicenter
      observational program 'KORMEN' that studied the efficacy of cortexin and
      memantinol in the treatment of cognitive impairment in patients with CCI. The
      study included 495 patients, 204 (41.2%) men and 291 (58.8%) women. Patients were
      stratified into two groups: cortexin group (n=388 (78.4%)) and cortexin +
      memantinol group. RESULTS AND CONCLUSION: A significant positive effect of
      treatment based on the scores on 4 cognitive scales was shown in both groups of
      patients. The addition of memantinol significantly improved cognitive functions
      in patients with severe cognitive impairment (r<0.05). The safety profile of the
      drugs was confirmed.

PMID- 29460903
TI  - [The efficacy of cocarnit in diabetic neuropathy].
AB  - AIM: To study the efficacy of the complex therapy, including cocarnit (group B
      vitamins, triphosadenine and nicotinamide), of diabetic neuropathy. MATERIAL AND
      METHODS: Forty-one patients with diabetes mellitus type 2 and distal symmetric
      sensorimotor polyneuropathy were examined. Patients were divided into 2 groups.
      Patients of the main group (n=26) received complex therapy, including cocarnit,
      and patients of the comparison group (n=15) received standard treatment. RESULTS
      AND CONCLUSION: The positive dynamics based on the VAS (r=0.0001), TSS
      (r=0.0001), NSS (r=0.001), NDS (r=0.0431), SF-36 (r=0.0008),
      electroneuromyographic results and glycated hemoglobin levels was observed in the
      main group. In patients of the comparison group, the positive dynamics was
      instable; the scores of clinical scales did not reach statistical significance.
      The results suggest the use of cocarnit in the complex treatment of patients with
      diabetic neuropathy.

PMID- 29460904
TI  - [Syndrome of autonomic dysfunction in children and adolescents].
AB  - AIM: To study clinical and pathophysiological symptoms of autonomic dysfunction
      syndrome in children and adolescents and assess the efficacy of its treatment
      with nooclerin. MATERIAL AND METHODS: Fifty-three patients, aged from 10 to 15
      years, with autonomic dysfunction syndrome were examined. All patients underwent
      neurological examination, assessment with the A.M. Vein's questionnaire of
      autonomic disorders, the 10 point Visual Analogous scale for headache and
      fatigue, the Spielberger-Khanin scale for anxiety, Kerdo index, Hildebrandt's
      coefficient, electrocardiography with clinoorthostatic test,
      electroencephalography, and TOVA psychophysiological test. RESULTS AND
      CONCLUSION: The signs of the asthenic-autonomic syndrome were characteristic of
      the clinical picture of disease. EEG results demonstrated the deficit of
      activation effects, predominance of synchronized effects of thalamic structures
      which led to the insufficient activation of cortical structures. These data
      support the high efficacy of nooclerin.

PMID- 29460905
TI  - [Multi-centre clinical assessment of the Russian language version of the
      Diagnostic Interview for Psychoses].
AB  - OBJECTIVES: The Diagnostic Interview for Psychoses (DIP) was developed to enhance
      the quality of diagnostic assessment of psychotic disorders. The aim of the study
      was the adaptation of the Russian language version and evaluation of its validity
      and reliability. MATERIAL AND METHODS: Ninety-eight patients with psychotic
      disorders (89 video recordings) were assessed by 12 interviewers using the
      Russian version of DIP at 7 clinical sites (in 6 cities of the Russian
      Federation). DIP ratings on 32 cases of a randomized case sample were made by 9
      interviewers and the inter-rater reliability was compared with the researchers'
      DIP ratings. Overall pairwise agreement and Cohen's kappa were calculated.
      Diagnostic validity was evaluated on the basis of comparing the researchers'
      ratings using the Russian version of DIP with the 'gold standard' ratings of the
      same 62 clinical cases from the Western Australia Family Study Schizophrenia
      (WAFSS). RESULTS: The mean duration of the interview was 47+/-21 minutes. The
      Kappa statistic demonstrated a significant or almost perfect level of agreement
      on the majority of DIP items (84.54%) and a significant agreement for the ICD-10
      diagnoses generated by the DIP computer diagnostic algorithm (kappa=0.68; 95% CI
      0.53,0.93). The level of agreement on the researchers' diagnoses was considerably
      lower (kappa=0.31; 95% CI 0.06,0.56). The agreement on affective and positive
      psychotic symptoms was significantly higher than agreement on negative symptoms
      (F(2,44)=20.72, p<0.001, eta2=0.485). The diagnostic validity of the Russian
      language version of DIP was confirmed by 73% (45/62) of the Russian DIP diagnoses
      matching the original WAFSS diagnoses. Among the mismatched diagnoses were 80
      cases with a diagnosis of F20 Schizophrenia in the medical documentation compared
      to the researchers' F20 diagnoses in only 68 patients and in 62 of the DIP
      computerized diagnostic outputs. The reported level of subjective difficulties
      experienced when using the DIP was low to moderate. CONCLUSION: The results of
      the study confirm the validity and reliability of the Russian version of the DIP
      for evaluating psychotic disorders. DIP can be recommended for use in education
      and training, clinical practice and research as an important diagnostic resource.

PMID- 29460906
TI  - [Changes in spatial relationships between catecholamine- and nitroxidergic
      neurons in the nuclei of the caudal brain stem in the development of
      hypertension].
AB  - AIM: To obtain the data on the spatial relationships between catecholamine (TH
      positive) and nitroxidergic (nNOS-positive) neurons in vasomotor nuclei of the
      medulla in different periods of hypertension development. MATERIAL AND METHODS:
      The experiment was performed on male Wistar rats (n=45) with induced renovascular
      hypertension (RVH). TH and nNOS in neurons of solitary tract nuclei, reticular
      small-and giant cell nuclei were detected using immunohistochemical methods.
      RESULTS AND CONCLUSION: The most early and severe changes in the intensity of
      reaction and amount of nNOS-positive neurons were noted in the solitary tract
      nucleus. Significant changes in the quantitative parameters of TH-positive
      neurons in RVH were identified only in the reticular giant cell nucleus but they
      appeared later and were less expressed compared to nNOS-positive cells. This
      resulted in the changes of spatial relationships between two types of neurons and
      remodeling of the bulbar region of the cardiovascular center.

PMID- 29460907
TI  - [Maturation of integrative sleep apparatus in children in normal and pathological
      condition].
AB  - AIM: To study and compare clinical characteristics of sleep macrostructure and
      sleep cycle organization during the night polysomnographic study in children with
      attention deficit hyperactivity disorder (ADHD) and obstructive sleep apnea
      syndrome (OSAS) aged from 6 to 9 years. MATERIAL AND METHODS: Polysomnography was
      performed in 40 children with ADHD and 20 children with OSAS. The control group
      included 20 healthy children. RESULTS AND CONCLUSION: The changes in sleep
      architectonics were unidirectional. Typical for the two groups of children was an
      increase in the latency of REM sleep and a reduction of its duration in total
      time of sleep. In children with ADHD, there was a significant decrease in the
      total number of sleep cycles, with a significant increase in the duration of the
      first sleep cycle. For an objective assessment of the rhythmic organization of
      ultradian rhythms, the authors propose a formula to calculate the maturity index
      of sleep in children older than 6 years. From the standpoint of evolutionary
      neuroscience, results should be considered as manifestations of dysontogenesis.

PMID- 29460908
TI  - [Association of sleep disorders with headache].
AB  - AIM: The aim of the present study was to investigate the connection of sleep
      disorders (SD) with a headache (HA) among the representative sample of
      population. MATERIAL AND METHODS: 1115 inhabitants of Chuvashia (491 men and 624
      women) aged from 18 to 70 years old have been interviewed (middle age 38.7+/-13.9
      years old); respondents under 18 and over 70 years old were not included into the
      research. There were 690 city residents, and 425 residents of the rural areas.
      The questionnaire approved earlier in the research of HA, and also the questions
      directed to identification of SD were used. One-way ANOVA, Chi-square test were
      used to compare variables of the groups. RESULTS: There were 718 (64.4%)
      respondents with SD and HA (the main group), 366 (23.8%) with HA without SD
      (comparative group), 16 (1.4%) with SD without HA, and 15 (1.3%) without SD and
      HA. The main group of the respondents authentically differed from other groups in
      older age, a larger number of women and villagers, presence of concomitant
      diseases in them. In the respondents with SD arose more often, pain had the
      combined (polymorphic) character, HA were more severe, localized in several areas
      of the head, but were of smaller duration. Among them there were more people with
      short sleep duration (<5 hours of night dream) and accepting sedative-hypnotic
      medications. HA without SD had a pricking character more often; the respondents
      more often slept in the afternoon, differed in higher level of education, and a
      rarer occurrence of cases of the increased arterial pressure. CONCLUSION: SD are
      often connected with HA, with their frequency, expressiveness and localization.
      Development of SD from HA are influenced by existence of concomitant diseases,
      age, gender and the place a residence. SD make the current of HA more severe.

PMID- 29460909
TI  - [Some reflections on the lasting importance of James Parkinson's Essay on the
      Shaking Palsy].

PMID- 29460910
TI  - [Alzheimer's disease].
AB  - Alzheimer's disease (AD) is a serious medical and social problem of our time,
      while remaining the most common cause of dementia in the elderly. The leading
      symptom in the clinical picture of the disease is a progressive loss of memory
      with further development of behavioral disorders. In the early stages of AD,
      patients are mostly managed by neurologists and differential diagnosis is carried
      out with a variety of neurodegenerative diseases. The authors present clinical
      criteria of AD diagnosis and consider diagnostic possibilities in the predementia
      stage using biological markers. With this purpose, modern concepts of the
      etiology and pathogenesis of AD and genetic aspects of pathology are considered.
      Contribution of many environmental factors to the initiation and progression of
      the disease process is evaluated. Mechanisms of cerebral amyloidosis and its
      characteristic neurological manifestations are considered.

PMID- 29460911
TI  - ['Masks' of acute neuroinfections and markers of differencial diagnosis].
AB  - AIM: To compare the medical history, clinical features, composition of
      cerebrospinal fluid (CSF), results of laboratory and instrumental examinations of
      patients with acute neuroinfections and differentiable diseases including a
      pseudoinflammatory variant of the acute stage of uncomplicated subarachnoid
      hemorrhage (SAH), consequences of traumatic brain injury (traumatic SAH, SAN
      combination with secondary purulent meningitis, posttraumatic nasal liquorrhea,
      intracerebral hematomas), abscesses and tumors of the brain, lymphoma with proven
      CNS. These diagnoses were mistakenly made to patients admitted to an infectious
      department. MATERIAL AND METHODS: Forty-six patients, aged from 18 to 83 years,
      hospitalized in the Department of neuroinfections and intensive care in 2010-2016
      were examined. Conventional clinical neurological, laboratory, instrumental
      (including MRI) examinations of patients, comprehensive examination of CSF
      samples, the study of markers of inflammation (C - reactive protein, CSF
      lactate), immunophenotyping of CSF cells were performed. RESULTS AND CONCLUSION:
      The misdiagnosis can be explained by the overestimation of such symptoms as the
      acute (in most cases) onset of the disease with increased body temperature to
      febrile levels, presence of meningeal syndrome, disorders of consciousness and
      focal symptoms of varying severity. The authors showed the errors and
      difficulties in the diagnosis, the role and importance of an integrated,
      interdisciplinary approach taking into account history, clinical data, results of
      CSF study, conventional and special methods of laboratory and instrumental
      examination of patients.

PMID- 29460912
TI  - [Cerebral insulin resistance: current concepts of the pathogenesis and possible
      therapeutic strategies].
AB  - The review presents current concepts about the problem of cerebral insulin
      resistance (IR). It has now been established that cerebral IR plays a key role in
      the pathogenesis of degenerative and metabolic diseases of the brain. Based on
      literature data and own clinical experience, the authors recommend to use the
      standardized extract of ginkgo biloba EGb761 as a cellular protector, which
      increases insulin sensitivity of cells and reduces atherogenesis, in order to
      improve cognitive functions and quality of life in patients with diabetes
      mellitus.

PMID- 29460913
TI  - [Migraine 'masks': differential diagnosis of acute headache].
AB  - Differential diagnosis of migraine, can be difficult, especially of migraine with
      aura. On the one hand, some diseases can produce symptoms similar to migraine
      (cerebral aneurysm before rupture, reversible cerebral vasoconstriction
      syndrome). On the other hand, migraine with aura and some other disorders are
      conditions that have common pathophysiological mechanisms (e.g., CADASIL and
      MELAS syndrome, antiphospholipid syndrome). Thirdly, clinical presentations of
      migraine are often difficult to distinguish from features of other headache
      conditions (migraine with aura - transient ischemic attack, migraine with visual
      aura - occipital epilepsy). The author discusses the differential diagnosis of
      acute headache, especially thunderclap headache, and main strategies of effective
      treatment of migraine attacks.

PMID- 29460914
TI  - [Alpha-lipoic acid in the treatment of diabetic polyneuropathy].
AB  - The issues of classification, pathogenesis, pathomorphology and treatment of
      diabetic polyneuropathy (DPN) are addressed. Pathogenetic mechanisms of the
      action of alpha-lipoic acid in treatment of DPN are justified. The authors
      present the results of randomized placebo-controlled trials of alpha-lipoic acid
      that revealed the high clinical efficacy and absence of side-effects even during
      the long-term treatment.

PMID- 29460915
TI  - [Nutritional support to patients with severe blood circulation disorders].
AB  - Eating disorders in stroke patients are always accompanied by structural and
      functional changes in the body, which leads to violations of adaptive reserves
      and trophic homeostasis. It is known that trophic homeostasis, together with
      optimal oxygen supply, forms the basis of the vital activity of the organism and
      is a necessary condition for overcoming of many pathological conditions.
      Insufficient nutrition leads to a slower recovery of patients, increases the risk
      of complications, predicts prolonged hospital stay, increases mortality.
      Inability of adequate feeding causes the necessity of obligatory administration
      of nutritional support to patients in a severe condition. The article provides a
      review of the main principles of organization of nutritional support in stroke
      patients and ways to assess its effectiveness.

PMID- 29460916
TI  - [Growth factors and neurotrophic control in the 'motoneuron - muscular fiber'
      system in children with cerebral palsy].
AB  - The article deals with the role of neurotrophic and growth factors in the
      development and functioning of the nervous system. The authors present general
      information on neurotrophic control and its role in the interaction of motor
      neurons and innervated muscle fibers.

PMID- 29460917
TI  - [An integrative basis of negative disorders of cognition in schizophrenia].
AB  - Based on the pathopsychological analysis, the author suggests a hypothesis of
      integrative basis of negative disorders of cognition in schizophrenia. The
      disorders are proposed to be related to the infringement of the general principle
      of CNS functioning - the domination of the process unifying cognitive, subjective
      psychological, neurophysiological components of individuality.

PMID- 29460918
TI  - Treatment of supragastric belching with cognitive behavioral therapy improves
      quality of life and reduces acid gastroesophageal reflux.
AB  - OBJECTIVES: Excessive supragastric belching (SGB) manifests as troublesome
      belching, and can be associated with reflux and significant impact on quality of
      life (QOL). In some GERD patients, SGB-associated reflux contributes to up to 1/3
      of the total esophageal acid exposure. We hypothesized that a cognitive
      behavioral intervention (CBT) might reduce SGB, improve QOL, and reduce acid
      gastroesophageal reflux (GOR). We aimed to assess the effectiveness of CBT in
      patients with pathological SGB. METHODS: Patients with SGB were recruited at the
      Royal London Hospital. Patients attended CBT sessions focused on recognition of
      warning signals and preventative exercises. Objective outcomes were the number of
      SGBs, esophageal acid exposure time (AET), and proportion of AET related to SGBs.
      Subjective evaluation was by patient-reported questionnaires. RESULTS: Of 51
      patients who started treatment, 39 completed the protocol, of whom 31 had a
      follow-up MII-pH study. The mean number of SGBs decreased significantly after CBT
      (before: 116 (47-323) vs. after 45 (22-139), P<0.0003). Sixteen of 31 patients
      were shown to have a reduction in SGB by >50%. In patients with increased AET at
      baseline, AET after CBT was decreased: 9.0-6.1% (P=0.005). Mean visual analog
      scale severity scores decreased after CBT (before: 260 (210-320) mm vs. after:
      140 (80-210) mm, P<0.0001). CONCLUSIONS: Cognitive behavioral therapy reduced the
      number of SGB and improved social and daily activities. Careful analysis of MII
      pH allows identification of a subgroup of GERD patients with acid reflux
      predominantly driven by SGB. In these patients, CBT can reduce esophageal acid
      exposure.

PMID- 29460919
TI  - A Role for Total Pancreatectomy and Islet Autotransplant in the Treatment of
      Chronic Pancreatitis.

PMID- 29460921
TI  - Measuring Change In Small Intestinal Histology In Patients With Celiac Disease.
AB  - Small intestinal histologic abnormalities in celiac disease include atrophy of
      the intestinal villi, hypertrophy of the crypts and lymphocytic infiltration of
      intraepithelial spaces and lamina propria. These findings are central to
      diagnosis and their severity and change over time are valuable to monitor disease
      course and response to therapy. Subjective methods to grade celiac disease
      histological severity include the Marsh-Oberhuber and Corazza-Villanacci systems.
      Quantitative histology uses villus height (Vh), crypt depth (Cd), and intra
      epithelial lymphocyte count (per 100 enterocytes) to provide objective measures
      of histologic changes including Vh:Cd ratio. Here we examine the available
      literature regarding these methodologies and support the use of quantitative
      histology as the preferred method for accurately and reproducibly demonstrating
      change of relevant histologic end points over time. We also propose a
      Quantitative-Mucosal Algorithmic Rules for Scoring Histology (Q-MARSH) system to
      partially align quantitative histology results with the traditional Marsh, Marsh
      Oberhuber, and Corazza-Villanacci systems. Q-MARSH can provide a standardized,
      objective, and quantitative histology scoring system for use as a clinical or
      research application.

PMID- 29460920
TI  - Long-Term Safety of In Utero Exposure to Anti-TNFalpha Drugs for the Treatment of
      Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.
AB  - OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti
      TNFalpha) drugs during pregnancy has received little attention. We aimed to
      compare the relative risk of severe infections in children of mothers with
      inflammatory bowel disease (IBD) who were exposed to anti-TNFalpha drugs in utero
      with that of children who were not exposed to the drugs. METHODS: Retrospective
      multicenter cohort study. Exposed cohort: children from mothers with IBD
      receiving anti-TNFalpha medication (with or without thiopurines) at any time
      during pregnancy or during the 3 months before conception. Non-exposed cohort:
      children from mothers with IBD not treated with anti-TNFalpha agents or
      thiopurines at any time during pregnancy or the 3 months before conception. The
      cumulative incidence of severe infections after birth was estimated using Kaplan
      Meier curves, which were compared using the log-rank test. Cox-regression
      analysis was performed to identify potential predictive factors for severe
      infections in the offspring. RESULTS: The study population comprised 841
      children, of whom 388 (46%) had been exposed to anti-TNFalpha agents. Median
      follow-up after delivery was 47 months in the exposed group and 68 months in the
      non-exposed group. Both univariate and multivariate analysis showed the incidence
      rate of severe infections to be similar in non-exposed and exposed children (1.6%
      vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In
      the multivariate analysis, preterm delivery was the only variable associated with
      a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero
      exposure to anti-TNFalpha drugs does not seem to be associated with increased
      short-term or long-term risk of severe infections in children.

PMID- 29460923
TI  - Microbiota: Bacteriophage diversity in the urinary microbiome.

PMID- 29460924
TI  - Prostate cancer: Numeracy and understanding of risk reduction of PSA screening.

PMID- 29460922
TI  - Cellular plasticity and the neuroendocrine phenotype in prostate cancer.
AB  - The success of next-generation androgen receptor (AR) pathway inhibitors, such as
      abiraterone acetate and enzalutamide, in treating prostate cancer has been
      hampered by the emergence of drug resistance. This acquired drug resistance is
      driven, in part, by the ability of prostate cancer cells to change their
      phenotype to adopt AR-independent pathways for growth and survival. Around one
      quarter of resistant prostate tumours comprise cells that have undergone cellular
      reprogramming to become AR-independent and to acquire a continuum of
      neuroendocrine characteristics. These highly aggressive and lethal tumours,
      termed neuroendocrine prostate cancer (NEPC), exhibit reactivation of
      developmental programmes that are associated with epithelial-mesenchymal
      plasticity and acquisition of stem-like cell properties. In the past few years,
      our understanding of the link between lineage plasticity and an emergent NEPC
      phenotype has considerably increased. This new knowledge can contribute to novel
      therapeutic modalities that are likely to improve the treatment and clinical
      management of aggressive prostate cancer.

PMID- 29460926
TI  - Optical activation of endogenous metabotropic glutamate receptor 4 (mGlu4) in the
      amygdala dynamically regulates symptoms associated with persistent inflammatory
      pain.

PMID- 29460927
TI  - Semiautomatic determination of arterial input function in DCE-MRI of the abdomen.
AB  - The goal of this study was to develop a semiautomatic segmentation technique of
      the abdominal aorta to determine the arterial input function (AIF). A total of 24
      patients having therapy naive abdominal cancers were imaged using DCE-MRI on a 3T
      MR scanner. DCE-MRI continued for 4.2 minutes with 2.1 seconds temporal
      resolution (120 acquisitions). Gadoteridol (0.1 mmol/kg) was infused
      intravenously at 30 seconds after starting DCE-MRI, and flushed with 20-ml saline
      (2 ml/s). Patients were instructed to hold breath after maximal inhalation, and
      repeat as needed to full inspiration. The location of the abdominal aorta was
      manually identified, but its segmentation and motion tracking were automatically
      implemented. AIFs determined in the aortic region with and without tracking
      motion were statistically compared. The aortic region was further segmented into
      multiple smaller regions, and the AIF change according to the size of the region
      of interest (ROI) was examined. The displacement of the abdominal aorta during
      DCE-MRI was 3.4+/-2.3 (mean+/-SD) mm. The root mean square error (RMSE) of AIF
      from the best fitting curve was 0.110+/-0.010 mM after motion correction, which
      was significantly smaller than that before motion correction (0.134+/-0.016 mM;
      p<0.001). The amplitude of AIF varied up to 15% according to the ROI size.
      However, when the radius of ROI was reduced more than 3 mm, the variation in AIF
      amplitude was less than 5%. Therefore the ROI having smaller radius than that of
      aorta will need to be used to determine a reliable AIF in abdominal DCE-MRI.

PMID- 29460928
TI  - Self-aggregation of water-dispersible nanocollagen helices.
AB  - Inspired by nature, collagen is an outstanding polypeptide utilized to exploit
      its bioactivity and material design for healthcare technologies. In this study,
      we describe the self-aggregation of water-dispersible nanocollagen helices upon
      solidification to fabricate different forms of natural collagen materials.
      Chemically extracted native collagen fibrils are uniform anisotropic
      nanoparticles with an average diameter of about 50 nm and a high aspect ratio.
      The as-prepared collagen nanofibrils are soluble in sodium acetate-acetic acid
      buffer and are dispersible in water, thus generating collagen liquids that are
      used as distinct biopolymer precursors for materials development. Our interesting
      findings indicate that water-dispersible collagen-derived alcogels undergo
      critical point drying to self-arrange hierarchical nanofibrils into helix bundles
      in collagen sponge-like aerogels. Notably, using lyophilization to remove water
      in the biopolymer dispersion, a full regeneration of solidified fibers is
      achieved, producing collagen aerogels with lightweight characteristics similar to
      natural cottons. The self-aggregation of water-dispersible collagen occurs under
      freeze-drying conditions to turn individual nanofibrils into sheets with layered
      structures in the aerogel networks. The development of transparent, water
      resistant collagen bioplastic-like membranes was achieved by supramolecular self
      assembly of water-dispersible collagen nanofibrils. Our efforts present a
      reliable concept in soft matter for creating promising collagen examples of
      liquids, hydrogels, aerogels, and membranes to increase utilization value of
      native collagen for biomedicine, pharmaceuticals, cosmetics, and nutrients.

PMID- 29460925
TI  - Clinical implications of PTEN loss in prostate cancer.
AB  - Genomic aberrations of the PTEN tumour suppressor gene are among the most common
      in prostate cancer. Inactivation of PTEN by deletion or mutation is identified in
      ~20% of primary prostate tumour samples at radical prostatectomy and in as many
      as 50% of castration-resistant tumours. Loss of phosphatase and tensin homologue
      (PTEN) function leads to activation of the PI3K-AKT (phosphoinositide 3-kinase
      RAC-alpha serine/threonine-protein kinase) pathway and is strongly associated
      with adverse oncological outcomes, making PTEN a potentially useful genomic
      marker to distinguish indolent from aggressive disease in patients with
      clinically localized tumours. At the other end of the disease spectrum,
      therapeutic compounds targeting nodes in the PI3K-AKT-mTOR (mechanistic target of
      rapamycin) signalling pathway are being tested in clinical trials for patients
      with metastatic castration-resistant prostate cancer. Knowledge of PTEN status
      might be helpful to identify patients who are more likely to benefit from these
      therapies. To enable the use of PTEN status as a prognostic and predictive
      biomarker, analytically validated assays have been developed for reliable and
      reproducible detection of PTEN loss in tumour tissue and in blood liquid
      biopsies. The use of clinical-grade assays in tumour tissue has shown a robust
      correlation between loss of PTEN and its protein as well as a strong association
      between PTEN loss and adverse pathological features and oncological outcomes. In
      advanced disease, assessing PTEN status in liquid biopsies shows promise in
      predicting response to targeted therapy. Finally, studies have shown that PTEN
      might have additional functions that are independent of the PI3K-AKT pathway,
      including those affecting tumour growth through modulation of the immune response
      and tumour microenvironment.

PMID- 29460929
TI  - Practical immune-barometer sensor for trivalent chromium ion detection using gold
      core platinum shell nanoparticle probes.
AB  - The technology progress of biosensors has markedly improved healthcare, disease
      diagnosis, environment monitoring, and food safety control over the past few
      decades. However, development of sensitive, robust, low-cost and portable assays
      for on-site bioanalysis is still a great challenge. In this study, we described a
      portable, feasible and miniaturized immune-barometer sensor (IBS), which can be
      used to sensitively measure the changes in a pressure signal, and we applied this
      IBS in the detection of Cr(iii). In this system, a competitive immunoassay was
      incorporated as a signaling technique for Cr(iii) detection. To generate a signal
      of pressure changes (DeltaP), Au@PtNPs (gold core platinum shell nanoparticles)
      were prepared for decomposing H2O2 to generate O2 in a sealed chamber. The
      expansion of gas volume was accurately detected using a sensitive barometer in
      the sealed reaction chamber. The DeltaP correlated well with Cr(iii)
      concentrations ranging from 0.39 to 25 ng mL-1. The limit of detection (LOD) of
      the IBS was estimated to be as low as 0.35 ng mL-1. Furthermore, the IBS has high
      specificity and high recovery for Cr(iii) detection in tap water samples (97.5%
      108.7%) and in the Pearl River water samples (95.6%-110.2%). Compared with the
      traditional enzyme-linked immunosorbent assay (ELISA), the IBS was observed to be
      more sensitive, of low-cost and portable for the on-site detection of Cr(iii).
      Therefore, the IBS is a promising potential method for the detection of heavy
      metals in aqueous solutions and many other fields.

PMID- 29460930
TI  - Transport and accumulation of plasma generated species in aqueous solution.
AB  - The interaction between cold atmospheric pressure plasma and liquids is receiving
      increasing attention for various applications. In particular, the use of plasma
      treated liquids (PTL) for biomedical applications is of growing importance, in
      particular for sterilization and cancer treatment. However, insight into the
      underlying mechanisms of plasma-liquid interactions is still scarce. Here, we
      present a 2D fluid dynamics model for the interaction between a plasma jet and
      liquid water. Our results indicate that the formed reactive species originate
      from either the gas phase (with further solvation) or are formed at the liquid
      interface. A clear increase in the aqueous density of H2O2, HNO2/NO2- and NO3- is
      observed as a function of time, while the densities of O3, HO2/O2- and ONOOH/ONOO
      are found to quickly reach a maximum due to chemical reactions in solution. The
      trends observed in our model correlate well with experimental observations from
      the literature.

PMID- 29460931
TI  - Nanocatalysts for hydrogen evolution reactions.
AB  - Hydrogen fuel is among the cleanest renewable resources and is the best
      alternative to fossil fuels for the future. Hydrogen can be best produced by
      means of electrolysis or photoelectrolysis of water among the various routes
      available for hydrogen production. So far, Pt has been recognized as the best
      electrode material for electrochemical hydrogen production. However, the cost of
      the catalyst, activity, and durability make Pt-catalyzed hydrogen production
      unsuitable on a commercial scale. It has hence become imperative to explore low
      cost, highly active and durable HER catalysts to replace platinum as a catalyst.
      This perspective provides key concepts and the current status of the research on
      the properties of nanocatalysts that influence the hydrogen evolution reaction.
      Important structural features controlling the surface chemistry (i.e. facets,
      defects, dopants), nature of supports (graphene, CNTs, black phosphorus), role of
      heteroatoms, media and morphology are the key points of discussion in this
      perspective.

PMID- 29460932
TI  - Site-specific binding of a water molecule to the sulfa drugs sulfamethoxazole and
      sulfisoxazole: a laser-desorption isomer-specific UV and IR study.
AB  - To determine the preferred water molecule binding sites of the polybasic sulfa
      drugs sulfamethoxazole (SMX) and sulfisoxazole (SIX), we have studied their
      monomers and monohydrated complexes through laser-desorption conformer-specific
      UV and IR spectroscopy. Both the SMX and SIX monomer adopt a single conformer in
      the molecular beam. On the basis of their conformer-specific IR spectra in the NH
      stretch region, these conformers were assigned to the SMX and SIX global minimum
      structures, both exhibiting a staggered sulfonamide group and an intramolecular C
      HO[double bond, length as m-dash]S hydrogen bond. The SMX-H2O and SIX-H2O
      complexes each adopt a single isomer in the molecular beam. Their isomeric
      structures were determined based on their isomer-specific IR spectra in the NH/OH
      stretch region. Quantum Theory of Atoms in Molecules analysis of the calculated
      electron densities revealed that in the SMX-H2O complex the water molecule
      donates an O-HN hydrogen bond to the heterocycle nitrogen atom and accepts an N
      HO hydrogen bond from the sulfonamide NH group. In the SIX-H2O complex, however,
      the water molecule does not bind to the heterocycle but instead donates an O
      HO[double bond, length as m-dash]S hydrogen bond to the sulfonamide group and
      accepts an N-HO hydrogen bond from the sulfonamide NH group. Both water complexes
      are additionally stabilized by a Cph-HOH2 hydrogen bond. Interacting Quantum
      Atoms analysis suggests that all intermolecular hydrogen bonds are dominated by
      the short-range exchange-correlation contribution.

PMID- 29460933
TI  - Mechanochemical methods for the preparation of intercalation compounds, from
      intercalation to the formation of layered double hydroxides.
AB  - Due to increasing interest in the development of advanced nanomaterials from
      nanosheets as building blocks, methods for the preparation of nanosheet materials
      and their hybrids have been studied carefully and extensively. In this review,
      studies of mechanochemical methods (solid-solid reactions under ambient
      conditions or solvent-free synthesis) for the preparation of intercalation
      compounds are summarized. Mechanochemical reactions without using solvent have
      operational advantages, such as their environmentally benign nature and the fact
      that separating and drying the products is not necessary. In addition to their
      advantages from green chemistry viewpoints, solid-state reactions have potential
      for the preparation of novel intercalation compounds which are not accessible by
      conventional solution-based methods.

PMID- 29460934
TI  - Hydrogen peroxide degradable conjugated polymer nanoparticles for fluorescence
      and photoacoustic bimodal imaging.
AB  - Herein we report the preparation of conjugated polymer nanoparticles via in situ
      Sonogashira polymerization to serve as a H2O2-degradable
      fluorescence/photoacoustic dual-modality contrast agent for cellular imaging.

PMID- 29460935
TI  - An exotic band structure of a supramolecular honeycomb lattice formed by a
      pancake pi-pi interaction between triradical trianions of triptycene
      tribenzoquinone.
AB  - A supramolecular honeycomb lattice was successfully formed by using triradical
      trianion species of triptycene tribenzoquinone (TT) which forms strong
      intermolecular pi-pi pancake bonds toward three directions. The crystal structure
      of Rb3TT.2H2O belongs to the hexagonal P6/m space group, the tight-binding band
      calculation of which reveals Dirac cones and flat bands.

PMID- 29460936
TI  - Norcrassin A, a novel C16 tetranorditerpenoid, and bicrotonol A, an unusual
      dimeric labdane-type diterpenoid, from the roots of Croton crassifolius.
AB  - A novel C16 tetranorditerpenoid, norcrassin A (1), and an unusual dimeric labdane
      type diterpenoid, bicrotonol A (2), were isolated from the roots of Croton
      crassifolius. Norcrassin A (1) featured a new carbon skeleton with an
      unprecedented 5/5/5/6 tetracyclic system. Bicrotonol A (2) possessed an unusual
      tetrahydroxypyran ring linkage connecting two labdane diterpenoid monomers. The
      structures of all compounds, including the absolute configuration, were
      elucidated by the interpretation of their NMR spectroscopic data, high resolution
      mass spectrometry, and single-crystal X-ray diffraction. A plausible biosynthetic
      pathway of 1 is proposed. The anti-Alzheimer's Disease (AD) activities of 1 and 2
      are also evaluated using the AD pathological model.

PMID- 29460937
TI  - A Cu-Zn nanoparticle promoter for selective carbon dioxide reduction and its
      application in visible-light-active Z-scheme systems using water as an electron
      donor.
AB  - Selective carbon dioxide photoreduction to produce formic acid was achieved under
      visible light irradiation using water molecules as electron donors, similar to
      natural plants, based on the construction of a Z-scheme light harvesting system
      modified with a Cu-Zn alloy nanoparticle co-catalyst. The faradaic efficiency of
      our Z-scheme system for HCOOH generation was over 50% under visible light
      irradiation.

PMID- 29460938
TI  - Spin-encoded subwavelength all-optical logic gates based on single-element
      optical slot nanoantennas.
AB  - Optical logic gates are important elements in optical computing and optical
      circuits. However, the footprints of the present optical logic gates are still on
      the micrometer scale. Further miniaturization of the logic gates to nanometer
      scale remains challenging. Here we propose, and demonstrate experimentally,
      subwavelength all-optical logic gates based on single-element optical slot
      nanoantennas. By employing a spin-encoded scheme, we achieve OR, AND, NOT, NAND
      and NOR logic gates via an L-shaped optical slot nanoantenna with a footprint of
      300 nm by 300 nm, and a XNOR logic gate via a rectangle optical slot nanoantenna
      with a footprint of 220 nm by 60 nm. The SPP launching and logic operation via
      mode coupling instead of path interference are integrated together at a single
      element nanoantenna, which considerably shrinks the dimensions of the device. The
      experimental results show the potential of the single optical slot nanoantenna in
      subwavelength all-optical logic computing and nanophotonic information
      processing.

PMID- 29460939
TI  - Cucurbit[6]uril-based multifunctional supramolecular assemblies: synthesis,
      removal of Ba(ii) and fluorescence sensing of Fe(iii).
AB  - A novel cucurbit[6]uril-based (Q[6]) supramolecular assembly
      {(NH4)2.Q[6].(HDTNB)2.2H2O} (1) with a three-dimensional (3D) framework structure
      was successfully constructed via outer-surface interactions between Q[6] and a
      flexible aromatic compound, 5,5'-dithiobis-(2-nitrobenzoic acid) (H2DTNB), as a
      structure-directing agent. It is interesting to find that assembly 1 can
      selectively capture Ba(ii) cations among the common alkaline-earth metal ions of
      Mg(ii), Ca(ii), Sr(ii) and Ba(ii), resulting in the formation of an isomorphic 3D
      assembly {Ba(H2O)2Q[6]}.(HDTNB)2 (2). Furthermore, both assemblies 1 and 2
      exhibit the selective sensing of Fe(iii) ions through fluorescence quenching,
      which has rarely been reported for Q[n]-based supramolecular assemblies.

PMID- 29460940
TI  - Copper-mediated domino C-H iodination and nitration of indoles.
AB  - An efficient and cost-effective copper-mediated aerobic oxidative C-H iodination
      and nitration of indoles via double C-H functionalization is reported. The domino
      process proceeds smoothly under mild aerobic conditions to give 3-iodo-2
      nitroindoles in one step with high regioselectivity and a broad substrate scope.
      The mechanism of the iodination step is proposed to proceed via a Cu(iii)-iodide
      species that undergoes electrophilic addition at the C3 position of the indole
      motif. The subsequent nitration step involves a sequence of C-H activation, nitro
      radical oxidative addition, and reductive elimination.

PMID- 29460941
TI  - Water-soluble platinum nanoparticles stabilized by sulfonated N-heterocyclic
      carbenes: influence of the synthetic approach.
AB  - The synthesis of metal nanoparticles (NPs) under controlled conditions in water
      remains a challenge in nanochemistry. Two different approaches to obtain platinum
      NPs, which involve the treatment of aqueous solutions of preformed sulfonated
      (NHC)Pt(ii) dimethyl complexes with carbon monoxide, and of (NHC)Pt(0) diolefin
      complexes with dihydrogen (NHC = N-heterocyclic carbene), are disclosed here. The
      resulting NPs were found to be highly stable in water under air for an indefinite
      time period. Coordination of the NHC ligands to the platinum surface via the
      carbenic carbon was monitored by solid-state NMR spectroscopy, and the presence
      of a platinum-carbon bond was unambiguously evidenced by the determination of a
      13C-195Pt coupling constant (1106 and 1050 Hz for NPs containing 13C labeled-NHC
      ligands and prepared under CO and H2, respectively). The coordination of CO to
      the (NHC)Pt(ii) precursors prior to formation of the NPs was confirmed by NMR
      spectroscopy. When using a disulfonated NHC ligand, a second coordination sphere
      containing bis(NHC)Pt(ii) complexes is described. Under CO, the formation of NPs
      was found to be slower than in a previously reported thermal method (Angew.
      Chem., Int. Ed., 2014, 53, 13220-13224), but led to NPs of similar sizes, whereas
      under H2, the synthesis of platinum NPs progressed even more slowly and produced
      larger NPs. In addition to the influence of the synthetic approach, the present
      study highlights the importance of ligand design for NP stabilization.

PMID- 29460942
TI  - Oxygen self-doped g-C3N4 with tunable electronic band structure for
      unprecedentedly enhanced photocatalytic performance.
AB  - As a fascinating conjugated polymer, graphitic carbon nitride (g-C3N4) has
      attracted much attention for solving the worldwide energy shortage and
      environmental pollution. In this work, for the first time we report oxygen self
      doping of solvothermally synthesized g-C3N4 nanospheres with tunable electronic
      band structure via ambient air exposure for unprecedentedly enhanced
      photocatalytic performance. Various measurements, such as XPS, Mott-Schottky
      plots, and density functional theory (DFT) calculations reveal that such oxygen
      doping can tune the intrinsic electronic state and band structure of g-C3N4via
      the formation of C-O-C bond. Our results show that the oxygen doping content can
      be controlled by the copolymerization of the precursors. As a consequence, the
      oxygen doped g-C3N4 shows excellent photocatalytic performance, with an RhB
      photodegradation rate of 0.249 min-1 and a hydrogen evolution rate of 3174 MUmol
      h-1 g-1, >35 times and ~4 times higher than that of conventional thermally made
      pure g-C3N4 (0.007 min-1 and 846 MUmol h-1 g-1, respectively) under visible
      light. Our work introduces a new route for the rational design and fabrication of
      doping modified g-C3N4 photocatalyst for efficient degradation of organic
      pollutants and H2 production.

PMID- 29460946
TI  - Lattice self-consistent field calculations of ring polymer brushes.
AB  - We reported the first systematic study using lattice self-consistent field (LSCF)
      calculations of ring homopolymer brushes grafted onto a flat and homogeneous
      surface and immersed in an explicit and athermal solvent, which are either
      uncompressed, compressed by a flat and impenetrable surface, or compressed by an
      identical brush. Our results clearly show that ring brushes are slightly less
      stretched than, thus nearly but not completely identical to, the "equivalent"
      linear brushes having half the chain length and double the grafting density. Our
      LSCF results are consistent with the molecular simulation results reported in the
      literature (Reith et al., Europhys. Lett., 2011, 95, 28003; Erbas and Paturej,
      Soft Matter, 2015, 11, 3139), except that Erbas and Paturej reported that the
      normal pressure of two opposing ring brushes is only half of the "equivalent"
      linear brushes at melt density.

PMID- 29460947
TI  - Correction: Effects of UV-B radiation on the infectivity of Magnaporthe oryzae
      and rice disease-resistant physiology in Yuanyang terraces.
AB  - Correction for 'Effects of UV-B radiation on the infectivity of Magnaporthe
      oryzae and rice disease-resistant physiology in Yuanyang terraces' by Xiang Li et
      al., Photochem. Photobiol. Sci., 2018, 17, 8-17.

PMID- 29460948
TI  - Guest-regulated chirality switching of planar chiral pseudo[1]catenanes.
AB  - pseudo[1]Catenane 3 is in a self-included conformation in chloroform, but in
      dichloromethane, it exists in an equilibrium between the self-included
      conformational state and a de-threading one. The planar chirality inversion of 3
      can be triggered by the host-guest complexation of 3 with adiponitrile G, but the
      extent of such chiral switching depends on the length of self-included
      bis(pyrazin-2-yloxy)alkane chains in 3 - longer chains are more favored than
      shorter ones in the inversion.

PMID- 29460949
TI  - An on-chip hybrid plasmonic light steering concentrator with ~96% coupling
      efficiency.
AB  - We, for the first time, propose and theoretically study a plasmonic light
      steering concentrator (PLSC) that is based on a hybrid photonic-plasmonic
      sandwich structure. In this device, a transverse electric (TE) polarization
      guided mode supported by a silicon-on-insulator (SOI) waveguide is vertically
      coupled to a metal-dielectric-metal sandwich structure, while the structure
      steers the light to a perpendicular metal taper and focuses the light on the apex
      of the taper with a small radius of 15 nm. Based on the coupled-mode theory, the
      two supermodes (quasi-TM modes) are clarified to illustrate the coupling
      mechanism of the device. We numerically obtain over 96% coupling efficiency at
      the 1500 nm telecommunication wavelength, and the mode width supported by the
      apex is limited laterally within the range of ~110 nm, where the field
      enhancement calculated is found to be more than 107 compared to that of light in
      the silicon waveguide.

PMID- 29460950
TI  - Thrombocytopenia in leukemia: Pathogenesis and prognosis.
AB  - Leukemias, a heterogeneous group of hematological disorders, are characterized by
      ineffective hematopoiesis and morphologic abnormalities of hematopoietic cells.
      Thrombocytopenia is a common problem among leukemia types that can lead to
      hemorrhagic complications in patients. The purpose of this review article is to
      identify the conditions associated with the incidence of thrombocytopenia in
      leukemias. It can be stated that although translocations have been considered
      responsible for this complication in many studies, other factors such as bone
      marrow failure, genes polymorphism, a mutation in some transcription factors, and
      the adverse effects of treatment could be associated with pathogenesis and poor
      prognosis of thrombocytopenia in leukemias. Considering the importance of
      thrombocytopenia in leukemias, it is hoped that the recognition of risk factors
      increasing the incidence of this complication in leukemic patients would be
      useful for prevention and treatment of this disorder.

PMID- 29460951
TI  - Quantifying linear enamel hypoplasia in Virunga Mountain gorillas and other great
      apes.
AB  - OBJECTIVE: Linear enamel hypoplasia (LEH) is a condition marked by localized
      reductions in enamel thickness, resulting from growth disruptions during dental
      development. We use quantitative criteria to characterize the depth of LEH
      defects and "normal" perikymata in great apes. We test the hypothesis that
      mountain gorillas have shallow defects compared to other taxa, which may have led
      to their underestimation in previous studies. MATERIALS AND METHODS: Previous
      attempts to characterize LEH morphology quantitatively have been limited in
      sample size and scope. We generated digital elevation models using optical
      profilometry (Sensofar PLu Neox) and extracted 2D coordinates using ImageJ to
      quantify depths in canines from three great ape genera (N = 75 perikymata; 255
      defects). RESULTS: All defect depths fall outside the distribution of perikymata
      depths. Mountain gorilla defects are significantly shallower than those of other
      great ape taxa examined, including western lowland gorillas. Females have
      significantly deeper defects than males in all taxa. The deepest defect belongs
      to a wild-captured zoo gorilla. Virunga mountain gorilla specimens collected by
      Dian Fossey exhibit deeper defects than those collected recently. DISCUSSION:
      Shallow defect morphology in mountain gorillas may have led to an underestimation
      of LEH prevalence in past studies. Defect depth is used as a proxy for insult
      severity, but depth might be influenced by inter- and intra-specific variation in
      enamel growth. Future studies should test whether severe insults are associated
      with deeper defects, as might be the case with Haloko, a wild-captured gorilla.
      Ongoing histologic studies incorporating associated behavioral records will test
      possible factors that underlie differences in defect morphology.

PMID- 29460952
TI  - Effects of hyaluronate-carboxymethylcellulose membranes on the clinical outcome
      of horses undergoing emergency exploratory celiotomy.
AB  - OBJECTIVE: To determine the influence of hyaluronate-carboxymethylcellulose (HA
      CMC) membranes applied to intestinal anastomoses or enterotomies on postoperative
      complications after emergency exploratory celiotomy. STUDY DESIGN: Multicenter
      retrospective case-controlled series. ANIMALS: Adult horses (59 in the HA-CMC
      group and 91 controls). METHODS: Medical records from 4 referral hospitals were
      searched for horses >=1 year of age, treated between 2008 and 2014 with emergency
      exploratory celiotomy, and surviving at least 24 hours postoperatively. Horses
      receiving repeat celiotomy during the same hospitalization were excluded. Horses
      who received HA-CMC were matched with controls who did not receive HA-CMC but had
      similar intestinal lesions and procedures at the same referral hospital.
      Postoperative complications (colic, nasogastric reflux, fever, incisional
      infection, and septic peritonitis), duration of hospitalization, and survival
      were compared between groups. Data were compared between horses by t test,
      Wilcoxon signed rank test, and chi2 test. RESULTS: The volume of nasogastric
      reflux at admission (P = .02) and the duration of administration of lidocaine
      after surgery (P = .02) were greater in horses with HA-CMC membranes than in
      controls. No difference in postoperative complications or survival was detected
      between groups: 48 of 59 (81%) horses treated with HA-CMC survived until
      discharge from the hospital compared with 80 of 91 (88%) horses in the control
      group (P = .27). Fifteen of 21 horses treated with HA-CMC and 30 of 43 horses in
      the control group survived >12 months after hospital discharge. CONCLUSION:
      Application of HA-CMC membranes to anastomoses or intestinal incisions did not
      influence postoperative complications or survival after emergency celiotomy
      compared with controls. CLINICAL SIGNIFICANCE: The safety and efficacy of HA-CMC
      membrane application to intestinal sites during colic surgery in horses is
      equivocal.

PMID- 29460953
TI  - Pressurized hot water extraction of beta-glucans from Cantharellus tubaeformis.
AB  - Cantharellus tubaeformis was processed by pressurized hot water extraction (80
      240 degrees C) with the aim of maximizing the extraction of oligomeric fractions,
      beta-glucans, and the in vitro antioxidant properties of the extracts. Increased
      severity of treatment enhanced the extraction yields above 62% at temperatures of
      210oC or higher, corresponding to the maximum beta-glucan yields. The highest
      antioxidant capacity was obtained at 170oC, although the highest content of
      phenolic compounds was obtained at the highest severity studied. This
      hydrothermal treatment can be considered a suitable process to obtain extracts
      with antioxidant properties and rich in beta-glucans.

PMID- 29460954
TI  - Peptide ligand-mediated endocytosis of nanoparticles to cancer cells: Cell
      receptor-binding- versus cell membrane-penetrating peptides.
AB  - The endocytosis-mediating performances of two types of peptide ligands, cell
      receptor binding peptide (CRBP) and cell membrane penetrating peptide (CMPP),
      were analyzed and compared using a common carrier of peptide ligands-human
      ferritin heavy chain (hFTH) nanoparticle. Twenty-four copies of a CMPP(human
      immunodeficiency virus-derived TAT peptide) and/or a CRBP (peptide ligand with
      strong and specific affinity for either human integrin(alphav beta3 ) or
      epidermal growth factor receptor I (EGFR) that is overexpressed on various cancer
      cells) were genetically presented on the surface of each hFTH nanopariticle. The
      quantitative level of endocytosis and intracellular localization of fluorescence
      dye-labeled CRBP- and CMPP-presenting nanoparticles were estimated in the in
      vitro cultures of integrin- and EGFR-overexpressing cancer and human dermal
      fibroblast cells(control). From the cancer cell cultures treated with the CMPP-
      and CRBP-presenting nanoparticles, it was notable that CRBPs resulted in
      quantitatively higher level of endocytosis than CMPP (TAT) and successfully
      transported the nanoparticles to the cytosol of cancer cells depending on
      concentration and treatment period of time, whereas TAT-mediated endocytosis
      localized most of the nanoparticles within endosomal vesicles under the same
      conditions. These novel findings provide highly useful informations to many
      researchers both in academia and in industry who are interested in developing
      anticancer drug delivery systems/carriers.

PMID- 29460955
TI  - A pilot study: Can the UFOV assessment be used as a repeated measure to determine
      timing of on-road assessment in stroke?
AB  - BACKGROUND/AIMS: Useful Field of View scores are predictive of on-road
      performance post-stroke. No objective data exist to determine if the Useful Field
      of View (UFOV) assessment can be used as a repeated measure in the post-stroke
      population to determine timing of occupational therapy on-road assessment as
      recovery occurs. The aims of this study were to determine whether there is a
      practice effect if the UFOV is administered at one, two and three months' post
      stroke and to assess optimal time post-stroke to refer to an on-road assessment.
      METHOD: Forty-two participants, 17 men (40.5%), with a mean age of 71 years (SD
      9.33) were randomly allocated to 1. Assessment group - UFOV at one, two and three
      months' post-stroke, 2. Control group-UFOV at three months' post-stroke.
      Parametric and non-parametric tests were utilised depending on data distribution.
      RESULTS: No significance was found between; three months' subtest 1 (P = 0.463),
      three months' subtest 2 (P = 0.729) and three months' subtest 3 (P = 0.534)
      between the assessment and control groups. Both group's scores were combined to
      examine pass/fail rates of UFOV assessment to indicate timing of referral to on
      road assessments. At one month, 16.9% stroke survivors passed the UFOV, when
      reassessed at three months 69.1% passed and 28.6% again failed. CONCLUSION:
      Improvements in scores at one month intervals over three months are due to
      improvements in abilities assessed by the UFOV as no practice effect was found to
      influence scores. UFOV scores performed at monthly intervals post-stroke can be
      used to guide the timing of an occupational therapy on-road assessment, with an
      increased likelihood of passing, as recovery occurs. This repeated use of the
      UFOV assessment can assist referral practices that best utilise driving
      rehabilitation programmes. Larger studies need to be conducted to confirm these
      results.

PMID- 29460956
TI  - Subacute thyroiditis in a patient with psoriasis treated with a tumor necrosis
      factor-alpha inhibitor.

PMID- 29460957
TI  - Mosaicism of de novo pathogenic SCN1A variants in epilepsy is a frequent
      phenomenon that correlates with variable phenotypes.
AB  - OBJECTIVE: Phenotypes caused by de novo SCN1A pathogenic variants are very
      variable, ranging from severely affected patients with Dravet syndrome to much
      milder genetic epilepsy febrile seizures plus cases. The most important
      determinant of disease severity is the type of variant, with variants that cause
      a complete loss of function of the SCN1A protein (alpha-subunit of the neuronal
      sodium channel Nav1.1) being detected almost exclusively in Dravet syndrome
      patients. However, even within Dravet syndrome disease severity ranges greatly,
      and consequently other disease modifiers must exist. A better prediction of
      disease severity is very much needed in daily practice to improve counseling,
      stressing the importance of identifying modifying factors in this patient group.
      We evaluated 128 participants with de novo, pathogenic SCN1A variants to
      investigate whether mosaicism, caused by postzygotic mutation, is a major
      modifier in SCN1A-related epilepsy. METHODS: Mosaicism was investigated by
      reanalysis of the pathogenic SCN1A variants using single molecule molecular
      inversion probes and next generation sequencing with high coverage. Allelic
      ratios of pathogenic variants were used to determine whether mosaicism was
      likely. Selected mosaic variants were confirmed by droplet digital polymerase
      chain reaction and sequencing of different tissues. Developmental outcome was
      classified based on available data on intelligence quotient and school
      functioning/education. RESULTS: Mosaicism was present for 7.5% of de novo
      pathogenic SCN1A variants in symptomatic patients. Mosaic participants were less
      severely affected than nonmosaic participants if only participants with
      truncating variants are considered (distribution of developmental outcome scores,
      Mann-Whitney U, P = .023). SIGNIFICANCE: Postzygotic mutation is a common
      phenomenon in SCN1A-related epilepsies. Participants with mosaicism have on
      average milder phenotypes, suggesting that mosaicism can be a major modifier of
      SCN1A-related diseases. Detection of mosaicism has important implications for
      genetic counseling and can be achieved by deep sequencing of unique reads.

PMID- 29460959
TI  - Identifying and prioritizing topics for evidence-based geriatric nursing practice
      guidelines in Korea.
AB  - BACKGROUND: Despite the increasing population of elderly individuals in Korea,
      there are no evidence-based geriatric nursing practice guidelines. AIM: This
      study aimed to identify and prioritize topics related to the development of
      evidence-based geriatric nursing practice guidelines in long-term care facilities
      in Korea. METHODS: To identify potential topics, 89 nurses responded to a
      questionnaire on activities that require further evidence and/or standardization
      in the long-term care facility setting. To prioritize these topics, 14 geriatric
      nursing experts completed surveys to prioritize five categories. RESULTS: The
      collected data included 240 clinical topics, which were classified into 41
      subcategories and 18 main categories. According to topic prioritization by the
      geriatric nursing experts, the following were the most heavily weighted
      categories: fall prevention, position change and prevention of pressure ulcers.
      CONCLUSIONS: The development of standardized guidelines based on these results
      may help improve the quality of geriatric care and quality of life of older
      individuals. The small number of respondents may be a limitation of this study,
      and further study is needed to expand the population. IMPLICATIONS FOR NURSING
      AND HEALTH POLICY: The development of evidence-based nursing guidelines based on
      the present findings will help improve the quality of nursing in long-term care
      facilities. Additionally, health policies and systems, such as introduction of a
      fee for nursing services for older individuals based on the evidence, are worth
      considering.

PMID- 29460960
TI  - Low-level TP53 mutational load antecedes clonal expansion in chronic lymphocytic
      leukaemia.

PMID- 29460958
TI  - Harnessing a methane-fueled, sediment-free mixed microbial community for
      utilization of distributed sources of natural gas.
AB  - Harnessing the metabolic potential of uncultured microbial communities is a
      compelling opportunity for the biotechnology industry, an approach that would
      vastly expand the portfolio of usable feedstocks. Methane is particularly
      promising because it is abundant and energy-rich, yet the most efficient methane
      activating metabolic pathways involve mixed communities of anaerobic
      methanotrophic archaea and sulfate reducing bacteria. These communities oxidize
      methane at high catabolic efficiency and produce chemically reduced by-products
      at a comparable rate and in near-stoichiometric proportion to methane
      consumption. These reduced compounds can be used for feedstock and downstream
      chemical production, and at the production rates observed in situ they are an
      appealing, cost-effective prospect. Notably, the microbial constituents
      responsible for this bioconversion are most prominent in select deep-sea
      sediments, and while they can be kept active at surface pressures, they have not
      yet been cultured in the lab. In an industrial capacity, deep-sea sediments could
      be periodically recovered and replenished, but the associated technical
      challenges and substantial costs make this an untenable approach for full-scale
      operations. In this study, we present a novel method for incorporating
      methanotrophic communities into bioindustrial processes through abstraction onto
      low mass, easily transportable carbon cloth artificial substrates. Using Gulf of
      Mexico methane seep sediment as inoculum, optimal physicochemical parameters were
      established for methane-oxidizing, sulfide-generating mesocosm incubations.
      Metabolic activity required >~40% seawater salinity, peaking at 100% salinity and
      35  degrees C. Microbial communities were successfully transferred to a carbon
      cloth substrate, and rates of methane-dependent sulfide production increased more
      than threefold per unit volume. Phylogenetic analyses indicated that carbon cloth
      based communities were substantially streamlined and were dominated by
      Desulfotomaculum geothermicum. Fluorescence in situ hybridization microscopy with
      carbon cloth fibers revealed a novel spatial arrangement of anaerobic
      methanotrophs and sulfate reducing bacteria suggestive of an electronic coupling
      enabled by the artificial substrate. This system: 1) enables a more targeted
      manipulation of methane-activating microbial communities using a low-mass and
      sediment-free substrate; 2) holds promise for the simultaneous consumption of a
      strong greenhouse gas and the generation of usable downstream products; and 3)
      furthers the broader adoption of uncultured, mixed microbial communities for
      biotechnological use.

PMID- 29460961
TI  - Type I Wenckebach second-degree AV block: A matter of definition.

PMID- 29460962
TI  - Glycosphingolipidomics of donkey milk by hydrophilic interaction liquid
      chromatography coupled to ESI and multistage MS.
AB  - Hydrophilic interaction liquid chromatography coupled to negative-ion
      electrospray linear ion-trap multiple-stage MS (HILIC-ESI-MSn , n = 2,3) was used
      to characterize polar lipids occurring in donkey milk. Besides the detection of
      abundant phospholipids, the structural characterization and content evaluation of
      minor glycosphingolipids (GSLs) were assessed. We report an unprecedented
      characterization of 11 hexosyl-ceramides (HexCer), 10 Hex2 Cer, and 4 Hex3 Cer.
      CID-MS/MS spectra in negative ion mode mainly afford information on the
      monosaccharide number and ceramide constitution (i.e., N-acyl residue and long
      chain base), whereas MS/MS/MS spectra on the ceramide anions allow to recognize
      for each GSL the sphingoid base. The occurrence of sphingosine (S), sphinganine
      (DS), and phytosphingosine (P) was inferred from the fragmentation patterns. The
      milk samples exhibit a relatively high number of phytosphingosine substitutes,
      perhaps because of the feeding of donkeys, mainly based on pasture grass.
      However, the incidence of hydroxylated species on the alpha-carbon of the acyl
      chain was also revealed. The fatty acid composition of N-acyl chains showed high
      values of long-chain saturated fatty acids such as 20:0, 22:0, 23:0, and 24:0. An
      average content of GSL is also provided and three representative mono-, di-, and
      tri-HexCer in donkey milk are the following: HexCer 18:0/24:1 phytosphingosine
      nonhydroxylated [PN] at m/z 862.6 as chloride adduct [M+Cl]- , and content 225.9
      +/- 2.8 MUg 100 mL-1 ; Hex2 Cer 18:0/16:0 sphinganine nonhydroxylated [DSN] at
      m/z 862.7 as deprotonated adduct [M-H]- , and content 70.8 +/- 1.4 MUg 100 mL-1 ;
      and Hex3 Cer 18:1/24:1 [SN] at m/z 1132.8 as [M-H]- , and content 38.5 +/- 0.7
      MUg 100 mL-1 .

PMID- 29460963
TI  - Water uptake can occur through woody portions of roots and facilitates localized
      embolism repair in grapevine.
AB  - Water acquisition is thought to be limited to the unsuberized surface located
      close to root tips. However, there are recurring periods when the unsuberized
      surfaces are limited in woody root systems, and radial water uptake across the
      bark of woody roots might play an important physiological role in hydraulic
      functioning. Using X-ray microcomputed tomography (microCT) and hydraulic
      conductivity measurements (Lpr ), we examined water uptake capacity of suberized
      woody roots in vivo and in excised samples. Bark hydration in grapevine woody
      roots occurred quickly upon exposure to water (c. 4 h). Lpr measurements through
      the bark of woody roots showed that it is permeable to water and becomes more so
      upon wetting. After bark hydration, microCT analysis showed that absorbed water
      was utilized to remove embolism locally, where c. 20% of root xylem vessels
      refilled completely within 15 h. Embolism removal did not occur in control roots
      without water. Water uptake through the bark of woody roots probably plays an
      important role when unsuberized tissue is scarce/absent, and would be
      particularly relevant following large irrigation events or in late winter when
      soils are saturated, re-establishing hydraulic functionality before bud break.

PMID- 29460964
TI  - Comparison between 8-methoxypsoralen and 5-aminolevulinic acid in killing T cells
      of photopheresis patients ex vivo.
AB  - BACKGROUND AND OBJECTIVE: Extracorporeal photopheresis (ECP), an established
      modality for cutaneous T-cell lymphoma (CTCL) and graft-versus-host disease,
      involves ex vivo treatment of isolated leukocytes of a patient with the
      photosensitizing drug 8-methoxypsoralen (8-MOP) and ultraviolet-A (UV-A) exposure
      before reinfusion back to the patient. However, 8-MOP binds to both diseased and
      normal cells and thus kills both types of the cells after UV-A illumination with
      little selectivity. Clinically, this modality gives only partial response in the
      majority of treated patients. 5-Aminolevulinic acid (5-ALA), a precursor of the
      potent photosensitizer protoporphyrin IX (PpIX), has been shown to selectively
      induce PpIX in activated T lymphocytes (T cells) and could be an alternative for
      8-MOP. The objectives of this study were to investigate ex vivo 5-ALA dark
      toxicity, 5-ALA-induced PpIX production, and photodynamic effect on T cells
      obtained from clinical ECP patients after the treatment of 5-ALA or 8-MOP plus a
      built-in certified UV-A source in the commercial TherakosTM Photopheresis System.
      MATERIALS AND METHODS: Flow cytometry was used to study dark cytotoxic effects of
      5-ALA on human leukocytes, to measure the production of 5-ALA-induced PpIX in
      CD25+ activated T cells from both diluted mononuclear cells and undiluted buffy
      coat samples of ECP patients and to compare photodynamic effects on CD4+ and CD8+
      T cells with 5-ALA/UV-A or 8-MOP/UV-A. RESULTS: No dark toxicity of 5-ALA on the
      leukocytes of ECP patients was seen at concentrations up to 10 mM for an
      incubation of up to 20 hours. 5-ALA-induced PpIX was produced more in CD25+
      activated T cells than resting T cells in both diluted mononuclear cells and
      undiluted buffy coat samples, although there was a huge variation of samples from
      different individual patients. The CD4+ and CD8+ T cells treated with 5-ALA/UV-A
      were killed more than those treated with 8-MOP/UV-A. CONCLUSION: These results
      suggest that 5-ALA/UV-A may have the potential for improving the efficacy of ECP.
      Lasers Surg. Med. 50:469-475, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29460965
TI  - Leukocytoclastic vasculitis associated with rivaroxaban.

PMID- 29460966
TI  - 'That proves my point': How mediums reconstrue disconfirmation in medium-sitter
      interactions.
AB  - Previous research has examined how the talk of mediums attends to the
      epistemological status of their readings. Such work has identified that mediums
      frequently use question-framed propositions that are typically confirmed by the
      sitter, thereby conferring epistemological status on the medium. This study seeks
      to investigate what happens when the sitter disconfirms the propositions of the
      medium. The study focuses on the ways in which such disconfirmation can be
      responded to such that it is reconstrued as evidence of the psychic nature of the
      medium's reading. Televised demonstrations of psychic readings involving British
      and US mediums and their sitters are analysed. The results suggest that mediums
      rework disconfirmation as proof in several ways: first, by emphasizing the
      different access that sitter and medium have to knowledge (e.g., about the
      future); second, as evidence that the medium has access to the actual voice of
      the deceased (and may therefore mishear what the deceased has said to them); and
      third, as revealing an important truth that has hitherto been concealed from the
      sitter. The implications of these findings are considered for cases where
      speakers bring different and potentially competing, epistemological resources to
      an interaction.

PMID- 29460967
TI  - Tumescent contravenom: murine model for prehospital treatment of Naja naja
      neurotoxic snake envenomation.
AB  - BACKGROUND: Snake envenomation is a neglected global health problem. There is a
      need for a prehospital treatment of neurotoxic snakebite that prolongs survival
      and allows time for a victim to reach a hospital for antivenom therapy. Tumescent
      epinephrine consists of a large volume of dilute epinephrine (2 mg/l) injected
      subcutaneously. It functions as "contravenom" by causing capillary
      vasoconstriction and delaying venom absorption. METHODS: A murine model of
      neurotoxic envenomation using lidocaine as a surrogate for neurotoxic snake venom
      was first developed in a pilot study. A lethal dose of lidocaine was injected
      subcutaneously into control and treatment groups. Mice in the treatment group
      were then treated with a tumescent infiltration of dilute epinephrine in saline,
      while control mice either received no treatment or tumescent infiltration with
      saline alone. The experiment was repeated using lethal doses of neurotoxic Naja
      naja cobra venom. The main end-points were survival rate and survival time.
      RESULTS: None of the control mice survived a lethal (LD100 ) dosage of
      subcutaneous lidocaine. Mice given an LD100 of subcutaneous lidocaine and treated
      immediately with tumescent epinephrine had 80% survival. Following LD50 doses of
      Naja naja venom, 50% of control mice survived, while 94% survived when treated
      immediately with tumescent epinephrine (P < 0.01). All animals died following
      LD100 doses of Naja naja venom, but survival was significantly prolonged (P <
      0.0001) by immediate tumescent epinephrine. CONCLUSIONS: Tumescent epinephrine,
      when given immediately after toxin injection, improves survival rates in mice
      following neurotoxic doses of lidocaine or Naja naja cobra venom.

PMID- 29460969
TI  - Exploring complaints by female and male patients at Swedish hospitals using a
      probabilistic graphical model.
AB  - BACKGROUND: Patients' complaints have been highlighted as important for
      constructively improving healthcare services. In so doing, it may be important to
      identify disparities in experiences based on patients' demographics, such as sex.
      AIM: To explore hospital recorded complaints addressing potential sex differences
      and whether complaints were reported by the patient or a relative. METHODS:
      Quantitative study of all 835 closed patient complaints during 2013 at three mid
      sized hospitals in Sweden. The complaints were categorisation based on perceived
      quality theory and analysed using a probabilistic graphical model. The findings
      were validated through qualitative interviews. FINDINGS: Female patients were
      more likely than male patients to report dissatisfaction with interpersonal
      issues, whereas male patients were more likely to report dissatisfaction with
      administration. If a complaint from a male patient had been reported by a
      relative, the matter was more likely to be interpersonal. Improvement suggestions
      were predominantly reported by staff. However, patients and relatives proved more
      likely than staff to report improvement suggestions when dissatisfied with
      interpersonal matters. CONCLUSION: Using a Bayesian network, this article
      suggests that complaints in health care should be more holistically understood
      and the factors should be viewed as interconnected. This article addresses
      complaints as an important source of identifying not only perceived healthcare
      deficiencies and sex disparities, but also improvement suggestions.

PMID- 29460968
TI  - Angioedema in chronic spontaneous urticaria is underdiagnosed and has a
      substantial impact: Analyses from ASSURE-CSU.
AB  - BACKGROUND: ASSURE-CSU revealed differences in physician and patient reporting of
      angioedema. This post hoc analysis was conducted to evaluate the actual rate of
      angioedema in the study population and explore differences between patients with
      and without angioedema. METHODS: This international observational study assessed
      673 patients with inadequately controlled chronic spontaneous urticaria (CSU).
      Physicians abstracted angioedema data from medical records, which were compared
      with patient-reported data. Patients in the Yes-angioedema category had
      angioedema reported in the medical record and a patient-reported source. For
      those in the No-angioedema category, angioedema was reported in neither the
      medical record nor a patient-reported source. Those in the Misaligned category
      had angioedema reported in only one source. Statistical comparisons between Yes
      angioedema and No-angioedema categories were conducted for measures of CSU
      activity, health-related quality of life (HRQoL), productivity and healthcare
      resource utilization (HCRU). Regression analyses explored the relationship
      between Dermatology Life Quality Index (DLQI) score and angioedema, adjusting for
      important covariates. RESULTS: Among evaluable patients, 259 (40.3%), 173 (26.9%)
      and 211 (32.8%) were in the Yes-angioedema, No-angioedema and Misaligned
      category, respectively. CSU activity and impact on HRQoL, productivity, and HCRU
      was greater for Yes-angioedema patients than No-angioedema patients. After
      covariate adjustment, mean DLQI score was significantly higher (indicating worse
      HRQoL) for patients with angioedema versus no angioedema (9.88 vs 7.27, P <
      .001). The Misaligned category had similar results with Yes-angioedema on all
      outcomes. CONCLUSIONS: Angioedema in CSU seems to be under-reported but has
      significant negative impacts on HRQoL, daily activities, HCRU and work compared
      with no angioedema.

PMID- 29460970
TI  - Clinical application research through reflection, interpretation and new
      understanding - a hermeneutic design.
AB  - The implementation of theoretical knowledge in clinical practice and the
      implementation of good clinical practice into theory have been of interest in
      caring science for the last 30 years. The aim of this article was to elaborate
      and discuss a methodology named clinical application research. The method is
      grounded in a hermeneutical design inspired by Gadamer's philosophy. The
      methodology, clinical application research, has been used in a research project A
      life in dignity and experiences from the researchers forms the bases for the
      elaboration and discussion. The project was performed in collaboration with
      residents, family caregivers and healthcare providers at six nursing homes in
      Scandinavia. The material for this article is based on the previous research,
      that is the results from 10 different articles showing the meaning of dignity and
      indignity in daily life in nursing homes. Data were generated from 56 individual
      interviews and 18 focus-group interviews with a total of 40 staff members with
      five to eight participants at every interview session. By reflection,
      interpretation and new understanding our results provide knowledge about dignity
      and how to preserve dignity for older people in an appropriate ethical way. The
      methodology was relevant for the research project A life in dignity and relevant
      to caring practice in nursing homes as it opens new possibilities and new ways of
      thinking when performing dignified care to older people.

PMID- 29460972
TI  - Alteration of renal excretion pathways in gentamicin-induced renal injury in
      rats.
AB  - The kidney plays a major part in the elimination of many drugs and their
      metabolites, and drug-induced kidney injury commonly alters either glomerular
      filtration or tubular transport, or both. However, the renal excretion pathway of
      drugs has not been fully elucidated at different stages of renal injury. This
      study aimed to evaluate the alteration of renal excretion pathways in gentamicin
      (GEN)-induced renal injury in rats. Results showed that serum cystatin C,
      creatinine and urea nitrogen levels were greatly increased by the exposure of GEN
      (100 mg kg-1 ), and creatinine concentration was increased by 39.7% by GEN (50 mg
      kg-1 ). GEN dose-dependently upregulated the protein expression of rOCT1,
      downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters,
      rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and
      the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100).
      GEN(50) did not alter the urinary excretion of inulin, but increased metformin
      and furosemide excretion. However, GEN(100) resulted in a significant decrease of
      the urinary excretion of inulin, metformin and p-aminohippurate. In addition,
      urinary metformin excretions in vivo were significantly decreased by GEN(100),
      but slightly increased by GEN(50). These results suggested that GEN(50) resulted
      in the induction of rOCTs-rMATE1 and rOAT3-rMRPs pathway, but not changed the
      glomerular filtration rate, and GEN(100)-induced acute kidney injury caused the
      downregulated function of glomerular filtration -rOCTs-rMATE1 and -rOAT1-rMRPs
      pathway.

PMID- 29460971
TI  - Quantification of Muscle Tissue Properties by Modeling the Statistics of
      Ultrasound Image Intensities Using a Mixture of Gamma Distributions in Children
      With and Without Cerebral Palsy.
AB  - OBJECTIVES: To investigate whether quantitative ultrasound (US) imaging, based on
      the envelope statistics of the backscattered US signal, can describe muscle
      properties in typically developing children and those with cerebral palsy (CP).
      METHODS: Radiofrequency US data were acquired from the rectus femoris muscle of
      children with CP (n = 22) and an age-matched cohort without CP (n = 14) at rest
      and during maximal voluntary isometric contraction. A mixture of gamma
      distributions was used to model the histogram of the echo intensities within a
      region of interest in the muscle. RESULTS: Muscle in CP had a heterogeneous echo
      texture that was significantly different from that in healthy controls (P <
      .001), with larger deviations from Rayleigh scattering. A mixture of 2 gamma
      distributions showed an excellent fit to the US intensity, and the shape and rate
      parameters were significantly different between CP and control groups (P < .05).
      The rate parameters for both the single gamma distribution and mixture of gamma
      distributions were significantly higher for contracted muscles compared to
      resting muscles, but there was no significant interaction between these factors
      (CP and muscle contraction) for a mixed-model analysis of variance. CONCLUSIONS:
      Ultrasound tissue characterization indicates a more disorganized architecture and
      increased echogenicity in muscles in CP, consistent with previously documented
      increases in fibrous infiltration and connective tissue changes in this
      population. Our results indicate that quantitative US can be used to objectively
      differentiate muscle architecture and tissue properties.

PMID- 29460973
TI  - Towards an analytic solution for pulsed CEST.
AB  - Chemical exchange saturation transfer (CEST) is an imaging method based on
      magnetization exchange between solutes and water. This exchange generates changes
      in the measured signal after off-resonance radiofrequency irradiation. Although
      the analytic solution for CEST with continuous wave (CW) irradiation has been
      determined, most studies are performed using pulsed irradiation. In this work, we
      derive an analytic solution for the CEST signal after pulsed irradiation that
      includes both short-time rotation effects and long-time saturation effects in a
      two-pool system corresponding to water and a low-concentration exchanging solute
      pool. Several approximations are made to balance the accuracy and simplicity of
      the resulting analytic form, which is tested against numerical solutions of the
      coupled Bloch equations and is found to be largely accurate for amides at high
      fields, but less accurate at the higher exchange rates, lower offsets and
      typically higher irradiation powers of amines.

PMID- 29460974
TI  - Significant alterations of 6-keto prostaglandin F1a and NO levels in spermatic
      vein plexus patients with varicocele.
AB  - To investigate the level variation of correlative factors between the spermatic
      vein plexus and peripheral blood in patients with varicocele, a total of 22
      patients diagnosed with varicocele were enrolled in the study. All patients were
      performed a testicular artery-sparing microsurgical varicocelectomy. During the
      operation, a blood sample from the left spermatic vein plexus and a peripheral
      blood sample were collected. A radioimmunoassay was used to determine the 6-keto
      prostaglandin F1a (6-keto-PGF1a ). A colorimetric method was performed to
      determine the NO. The enzyme immunoassay method was used to determine the
      creatinine, urea nitrogen, adrenaline, noradrenaline, dopamine and 5-HT. The mean
      age of all patients was 29.3 +/- 7.8 years. Compared with the level of 6-keto
      PGF1a and NO in the peripheral blood, 6-keto-PGF1a and NO were significantly
      increased in left spermatic vein plexus (347.3 (230.8-415.1) versus 99.7 (80.4
      119.9) pg/ml and 192.3 +/- 178.5 versus 107.1 +/- 73.6 MUmol/L, p < .05). There
      were no differences in the level of creatinine, urea nitrogen, adrenaline,
      noradrenaline, dopamine and 5-HT between the peripheral blood and left spermatic
      vein plexus (p > .05). The 6-keto-PGF1a and NO concentrations in left spermatic
      vein plexus were significantly higher than that in peripheral blood patients with
      varicocele.

PMID- 29460975
TI  - Reply: MoCA for cognitive screening in Parkinson's disease: Beware of floor
      effect.

PMID- 29460976
TI  - Vein wrapping promotes M2 macrophage polarization in a rat chronic constriction
      injury model.
AB  - Although the therapeutic potential of vein wrapping (VW) for recurrent
      compressive neuropathy has been widely reported, the mechanisms underlying this
      technique have not been characterized. M2 macrophages induced by interleukin-4
      (IL-4) or interleukin-10 (IL-10) have an anti-inflammatory function and play an
      important role in peripheral nerve repair. To evaluate whether VW promotes M2
      polarization, we divided chronic constriction injury (CCI) rats into untreated
      and VW (CCI + VW)-treated groups. Pain withdrawal thresholds in both groups were
      evaluated using von Frey filaments. Expression of the anti-inflammatory cytokines
      IL-4 and IL-10 in vein and nerve were quantified using real time polymerase chain
      reaction (RT-PCR), and expression of the anti-inflammatory M2 macrophage markers
      CD206 and arginase-1 (Arg1) after VW was assessed by RT-PCR and
      immunohistochemistry. To evaluate the effect of exogenous IL-4 or IL-10 on M2
      macrophage-marker expression, CD11b-positive macrophages isolated from sciatic
      nerve were stimulated with recombinant IL-4 and IL-10. VW significantly increased
      the pain withdrawal threshold. IL-4 and IL-10 mRNA expression was higher in veins
      than in the sciatic nerve. VW significantly increased CD206 and Arg1 mRNA
      expression compared to the CCI group. The number of CD206- and Arg1
      immunoreactive cells in nerve bundles was twofold higher in the CCI + VW than CCI
      group. Application of exogenous IL-4 doubled CD206 and Arg1 mRNA expression in
      CD11b-positive macrophages. These results show that vein-derived IL-4 potentiates
      the benefit of VW through the activation of M2 macrophages in the sciatic nerve.
      Our results may help to optimize current procedures for treating recurrent
      compressive neuropathy. (c) 2018 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res.

PMID- 29460977
TI  - Development of a screening tool using electronic health records for undiagnosed
      Type 2 diabetes mellitus and impaired fasting glucose detection in the Slovenian
      population.
AB  - AIM: To develop and validate a simplified screening test for undiagnosed Type 2
      diabetes mellitus and impaired fasting glucose for the Slovenian population
      (SloRisk) to be used in the general population. METHODS: Data on 11 391 people
      were collected from the electronic health records of comprehensive medical
      examinations in five Slovenian healthcare centres. Fasting plasma glucose as well
      as information related to the Finnish Diabetes Risk Score questionnaire,
      FINDRISC, were collected for 2073 people to build predictive models.
      Bootstrapping-based evaluation was used to estimate the area under the receiver
      operating characteristic curve performance metric of two proposed logistic
      regression models as well as the Finnish Diabetes Risk Score model both at
      recommended and at alternative cut-off values. RESULTS: The final model contained
      five questions for undiagnosed Type 2 diabetes prediction and achieved an area
      under the receiver-operating characteristic curve of 0.851 (95% CI 0.850-0.853).
      The impaired fasting glucose prediction model included six questions and achieved
      an area under the receiver-operating characteristic curve of 0.840 (95% CI 0.839
      0.840). There were four questions that were included in both models (age, sex,
      waist circumference and blood sugar history), with physical activity selected
      only for undiagnosed Type 2 diabetes and questions on family history and
      hypertension drug use selected only for the impaired fasting glucose prediction
      model. CONCLUSIONS: This study proposes two simplified models based on FINDRISC
      questions for screening of undiagnosed Type 2 diabetes and impaired fasting
      glucose in the Slovenian population. A significant improvement in performance was
      achieved compared with the original FINDRISC questionnaire. Both models include
      waist circumference instead of BMI.

PMID- 29460978
TI  - Use of Tisseel fibrin glue for a recurrent cheek haematoma after Mohs
      micrographic surgery.

PMID- 29460979
TI  - Management of naevus sebaceous: a national survey of UK dermatologists and
      plastic surgeons.
AB  - Naevus sebaceous (NS) is a congenital cutaneous hamartoma, which typically occurs
      on the head and neck. Historically, the treatment of choice was excision in
      infancy because of the potential for malignant transformation; however, recent
      studies suggest that this risk is < 1% and unlikely in childhood. We sent a
      questionnaire to UK dermatologists and plastic surgeons to investigate current
      management practice of NS. We found that almost a third of dermatologists still
      recommend excision for malignancy prevention, while over 90% of plastic surgeons
      consider excision, with 64% citing malignancy prevention as the reason. Plastic
      surgeons most commonly recommended excision in childhood, whereas dermatologists
      waited until adulthood. We have shown there is significant variation in practice
      across the UK in the management of naevus NS. It is important that patients
      across the UK receive the same standard of care, and therefore we advocate the
      development of evidence-based guidance for treatment of naevus NS.

PMID- 29460980
TI  - Quantitative, clinically relevant acoustic measurements of focal embouchure
      dystonia.
AB  - BACKGROUND: Focal embouchure dystonia impairs orofacial motor control in wind
      musicians and causes professional disability. A paucity of quantitative measures
      or rating scales impedes the objective assessment of treatment efficacy.
      OBJECTIVES: We quantified specific features of focal embouchure dystonia using
      acoustic measures and developed a metric to assess severity across multiple
      domains of symptomatic impairment. METHODS: We recruited 9 brass musicians with
      and 6 without embouchure dystonia. The following 4 domains of symptomatic
      dysfunction in focal embouchure dystonia were identified: pitch inaccuracy, sound
      instability and tremor, sound breaks, and timing variability. Musicians performed
      sustained tones and sequences, and then acoustic variables within each domain
      were quantified. A composite brass acoustic severity score composed of these
      variables was validated against clinical global impressions of severity. RESULTS:
      Musicians with dystonia performed worse in acoustic domains of pitch inaccuracy
      (median: dystonia = 100%, control = 62%), instability (median shimmer: dystonia =
      3%, control = 2%), and breaks (median: dystonia = 0.34%, control = 0.05%). Tremor
      in embouchure dystonia was 5 to 8 Hz, intermittent, and variable in amplitude.
      Rhythmic variability did not differ between groups. Participants with embouchure
      dystonia had different patterns of impairment across variables. Composite
      severity scores strongly predicted clinical global impression of severity (R2  =
      0.95). CONCLUSIONS: Acoustic variables distinguish musicians with embouchure
      dystonia from controls and reflect different types of symptomatic impairments.
      Our composite acoustic severity score predicts severity of clinical global
      impression for musicians with different patterns of symptomatic impairment and
      may provide a foundation for developing a clinical rating scale. (c) 2018
      International Parkinson and Movement Disorder Society.

PMID- 29460981
TI  - Non-invasive brain stimulation of motor cortex induces embodiment when integrated
      with virtual reality feedback.
AB  - Previous evidence highlighted the multisensory-motor origin of embodiment - that
      is, the experience of having a body and of being in control of it - and the
      possibility of experimentally manipulating it. For instance, an illusory feeling
      of embodiment towards a fake hand can be triggered by providing synchronous visuo
      tactile stimulation to the hand of participants and to a fake hand or by asking
      participants to move their hand and observe a fake hand moving accordingly
      (rubber hand illusion). Here, we tested whether it is possible to manipulate
      embodiment not through stimulation of the participant's hand, but by directly
      tapping into the brain's hand representation via non-invasive brain stimulation.
      To this aim, we combined transcranial magnetic stimulation (TMS), to activate the
      hand corticospinal representation, with virtual reality (VR), to provide matching
      (as contrasted to non-matching) visual feedback, mimicking involuntary hand
      movements evoked by TMS. We show that the illusory embodiment occurred when TMS
      pulses were temporally matched with VR feedback, but not when TMS was
      administered outside primary motor cortex, (over the vertex) or when stimulating
      motor cortex at a lower intensity (that did not activate peripheral muscles).
      Behavioural (questionnaires) and neurophysiological (motor-evoked-potentials, TMS
      evoked-movements) measures further indicated that embodiment was not explained by
      stimulation per se, but depended on the temporal coherence between TMS-induced
      activation of hand corticospinal representation and the virtual bodily feedback.
      This reveals that non-invasive brain stimulation may replace the application of
      external tactile hand cues and motor components related to volition, planning and
      anticipation.

PMID- 29460983
TI  - Transcriptional profiling of synovium in a porcine model of early post-traumatic
      osteoarthritis.
AB  - To determine the transcriptional profile of synovium during the molecular phase
      of post-traumatic osteoarthritis, anterior cruciate ligament transections (ACL)
      were performed in 36 Yucatan minipigs. Equal numbers were randomly assigned to no
      further treatment, ACL reconstruction or repair. Perimeniscal synovium for
      histopathology and RNA-sequencing was harvested at 1 and 4 weeks post-operatively
      and from six healthy control animals. Microscopic synovitis scores significantly
      worsened at 1 (p < 0.001) and 4 weeks (p = 0.003) post-surgery relative to
      controls, and were driven by intimal hyperplasia and increased stromal
      cellularity without inflammatory infiltrates. Synovitis scores were similar
      between no treatment, reconstruction, and repair groups (p >= 0.668). Relative to
      no treatment at 1 week, 88 and 367 genes were differentially expressed in the
      reconstruction and repair groups, respectively (227 and 277 at 4 weeks). Relative
      to controls and with the treatment groups pooled, 1,683 transcripts were
      concordantly differentially expressed throughout the post-surgery time-course.
      Affected pathways included, proteolysis_connective tissue degradation (including
      upregulations of protease-encoding MMP1, MMP13, and ADAMTS4), and
      development_cartilage development (including upregulations of ACAN, SOX9, and
      RUNX2), among others. Using linear regression, significant associations of post
      surgery synovial expression levels of 20 genes with the articular cartilage
      glycosaminoglycan loss were identified. These genes were predominantly related to
      embryonic skeletal system development and included RUNX2. In conclusion, this
      study confirmed an increased synovial expression of genes that may serve as
      targets to prevent cartilage degradation, including MMP1, MMP13, and ADAMTS4, in
      knees with microscopic synovitis and cartilage proteoglycan loss. Attractive
      novel targets include regulators of embryonic developmental processes in
      synovium. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals,
      Inc. J Orthop Res.

PMID- 29460982
TI  - Lifetime exposure to estrogen and progressive supranuclear palsy: Environmental
      and Genetic PSP study.
AB  - BACKGROUND: Studies suggesting a protective effect of estrogen in
      neurodegenerative diseases prompted us to investigate this relationship in
      progressive supranuclear palsy (PSP). METHODS: This case-control study evaluated
      the self-reported reproductive characteristics and estrogen of 150 women with PSP
      and 150 age-matched female controls who participated in the Environmental Genetic
      PSP study. Conditional logistic regression models were generated to examine
      associations of PSP with estrogen. RESULTS: There was no association between
      years of estrogen exposure duration and PSP. There was a suggestion of an inverse
      association between composite estrogen score and PSP that did not reach
      statistical significance (P = .06). Any exposure to estrogen replacement therapy
      halved the risk of PSP (odds ratio = 0.52; 95% confidence interval = 0.30-0.92; P
      = .03). Among PSP cases, earlier age at menarche was associated with better
      performance on Hoehn and Yahr stage (beta = -0.60; SE = 0.26; P = .02) and
      Unified Parkinson's Disease Rating Scale II score (beta = -5.19; SE = 2.48; P =
      .04) at clinical examination. CONCLUSIONS: This case-control study suggests a
      protective role of lifetime estrogen exposure in PSP. Future studies will be
      needed to confirm this association. (c) 2018 International Parkinson and Movement
      Disorder Society.

PMID- 29460985
TI  - Characterization of cellular and matrix alterations in the early pathogenesis of
      osteochondritis dissecans in pigs using second harmonic generation and two-photon
      excitation fluorescence microscopy.
AB  - Osteochondritis dissecans is a joint disease that is observed in several species.
      The disease can develop as a cause of ischemic chondronecrosis in the epiphyseal
      growth cartilage. Some lesions of chondronecrosis undergo spontaneous resolution,
      but it is not possible to predict whether a lesion will resolve or progress and
      require intervention. Proliferation of cells into clusters occurs at the lesion
      margin, but it is unclear if the clusters have a repair function. The aims of the
      current study were to examine clusters and potential matrix changes in response
      to ischemic chondronecrosis in the distal femur of 10 pigs aged 70-180 days using
      advanced microscopy based on two-photon excitation fluorescence and second
      harmonic generation. These microscopy techniques can perform 3D imaging of cells
      and collagen without staining. The results indicated a lower collagen density in
      the chondronecrotic areas compared to the normal growth cartilage, and fissures
      and breaks in the matrix integrity were demonstrated that potentially can
      propagate and cause osteochondritis dissecans. A higher number of cells in
      clusters was correlated with reduction in collagen density in the lesions. Some
      of the cells in the clusters had a morphology similar to progenitor cells,
      suggesting a potential repair role of the clusters. The study has shed further
      light on the secondary responses after initial lesion formation, which
      information can be of potential use to create models that can predict lesion
      progression and that may hence avoid unnecessary interventions in the future. (c)
      2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
      Res.

PMID- 29460984
TI  - A laboratory high-throughput glass chamber using dynamic headspace TD-GC/MS
      method for the analysis of whole Brassica napus L. plantlet volatiles under
      cadmium-related abiotic stress.
AB  - INTRODUCTION: The dynamic headspace sampling technique using thermal desorption,
      gas chromatography-mass spectrometry (TD-GC/MS) is a powerful method for
      analysing plant emissions of volatile organic compounds (VOCs), and experiments
      performed in sterile and controlled conditions can be useful for VOC metabolism
      investigations. OBJECTIVE: The main purpose of this study was to set up a
      laboratory high-throughput glass chamber for whole plant volatiles analysis.
      Brassica napus L. plantlets were tested with the developed system to better
      understand the relationship between low emission of induced terpene and cadmium
      (Cd)-related abiotic stress. METHODOLOGY: VOCs emitted by 28-day-old Brassica
      napus L. plantlets cultivated in vitro were trapped with our device using
      adsorbent cartridges that were desorbed with a thermal desorption unit before
      cryofocusing with a cooled injection system and programmable temperature
      vaporising inlet into an HP-5 ms GC column. Terpene detection and quantitation
      from chromatogram profiles were acquired using selected ion monitoring (SIM) mode
      during full scan analysis and mass spectra were obtained with a quadrupole-type
      mass spectrometer. RESULTS: The new trapping method produced reliable qualitative
      profiles of oilseed rape VOCs. Typical emissions of monoterpenes (myrcene,
      limonene) and sesquiterpenes (beta-elemene, (E,E)-alpha-farnesene) were found for
      the different concentrations tested. One-way analysis of variance for
      quantitative results of (E,E)-alpha-farnesene emission rates showed a Cd
      concentration effect. CONCLUSION: This inexpensive glass chamber has potential
      for wide application in laboratory sterile approach and replicated research.
      Moreover, the non-invasive dynamic sampling technique could also be used to
      analyse volatiles under both abiotic and biotic stresses.

PMID- 29460986
TI  - Text-mined phenotype annotation and vector-based similarity to improve
      identification of similar phenotypes and causative genes in monogenic disease
      patients.
AB  - The genetic diagnosis of rare monogenic diseases using exome/genome sequencing
      requires the true causal variant(s) to be identified from tens of thousands of
      observed variants. Typically a virtual gene panel approach is taken whereby only
      variants in genes known to cause phenotypes resembling the patient under
      investigation are considered. With the number of known monogenic gene-disease
      pairs exceeding 5,000, manual curation of personalized virtual panels using
      exhaustive knowledge of the genetic basis of the human monogenic phenotypic
      spectrum is challenging. We present improved probabilistic methods for estimating
      phenotypic similarity based on Human Phenotype Ontology annotation. A limitation
      of existing methods for evaluating a disease's similarity to a reference set is
      that reference diseases are typically represented as a series of binary
      (present/absent) observations of phenotypic terms. We evaluate a quantified
      disease reference set, using term frequency in phenotypic text descriptions to
      approximate term relevance. We demonstrate an improved ability to identify
      related diseases through the use of a quantified reference set, and that vector
      space similarity measures perform better than established information content
      based measures. These improvements enable the generation of bespoke virtual gene
      panels, facilitating more accurate and efficient interpretation of genomic
      variant profiles from individuals with rare Mendelian disorders. These methods
      are available online at https://atlas.genetics.kcl.ac.uk/~jake/cgi
      bin/patient_sim.py.

PMID- 29460987
TI  - MoCA for cognitive screening in Parkinson's disease: Beware of floor effect.

PMID- 29460988
TI  - Monitoring the future survey: Important messages for nursing practice.

PMID- 29460989
TI  - Attitudes toward adolescent self-harm and its prevention: The views of those who
      self-harm and their peers.
AB  - PROBLEM: Adolescent self-harm is a common phenomenon; however, little is known
      about young peoples' attitudes toward self-harm and what they believe can be done
      to prevent it. This study aimed to identify adolescents' attitudes about self
      harm and their perspectives on preventing it. METHODS: A cross-sectional
      anonymous survey was administered to 856 post-primary school students across 11
      schools in Dublin, Ireland. Attitudes toward self-harm were captured through a
      five-item scale and views on prevention of self-harm were captured through an
      open-ended survey question. Responses from those who self-harmed and those who
      did not were compared to identify differences. FINDINGS: Significant differences
      were identified between those who self-harmed and their peers. Those who self
      harmed were less likely to believe that self-harm was carried out to get
      attention or was a result of loneliness or depression; they were more likely to
      believe that self-harm was impulsive. Findings demonstrated that a majority of
      young people believed that self-harm could be prevented and a number of
      preventative strategies were identified. CONCLUSIONS: It is important that the
      views of adolescents are incorporated into the design and delivery of youth
      friendly services and that there is a focus on increasing awareness of the youth
      orientated services that currently exist.

PMID- 29460990
TI  - Beta-gamma burst stimulations of the inferior olive induce high-frequency
      oscillations in the deep cerebellar nuclei.
AB  - The cerebellum displays various sorts of rhythmic activities covering both low-
      and high-frequency oscillations. These cerebellar high-frequency oscillations
      were observed in the cerebellar cortex. Here, we hypothesised that not only is
      the cerebellar cortex a generator of high-frequency oscillations but also that
      the deep cerebellar nuclei may also play a similar role. Thus, we analysed local
      field potentials and single-unit activities in the deep cerebellar nuclei before,
      during and after electric stimulation in the inferior olive of awake mice. A high
      frequency oscillation of 350 Hz triggered by the stimulation of the inferior
      olive, within the beta-gamma range, was observed in the deep cerebellar nuclei.
      The amplitude and frequency of the oscillation were independent of the frequency
      of stimulation. This oscillation emerged during the period of stimulation and
      persisted after the end of the stimulation. The oscillation coincided with the
      inhibition of deep cerebellar neurons. As the inhibition of the deep cerebellar
      nuclei is related to inhibitory inputs from Purkinje cells, we speculate that the
      oscillation represents the unmasking of the synchronous activation of another
      subtype of deep cerebellar neuronal subtype, devoid of GABA receptors and under
      the direct control of the climbing fibres from the inferior olive. Still, the
      mechanism sustaining this oscillation remains to be deciphered. Our study sheds
      new light on the role of the olivo-cerebellar loop as the final output control of
      the intercerebellar circuitry.

PMID- 29460991
TI  - Time trends and occupational variation in the incidence of testicular cancer in
      the Nordic countries.
AB  - OBJECTIVE: To describe the trends and occupational variation in the incidence of
      testicular cancer in the Nordic countries utilising national cancer registries,
      NORDCAN (NORDCAN project/database presents the incidence, mortality, prevalence
      and survival from >50 cancers in the Nordic countries) and NOCCA (Nordic
      Occupational Cancer) databases. PATIENTS AND METHODS: We obtained the incidence
      data of testicular cancer for 5-year periods from 1960-1964 to 2000-2014 and for
      5-year age-groups from the NORDCAN database. Morphological data on incident cases
      of seminoma and non-seminoma were obtained from national cancer registries. Age
      standardised incidence rates (ASR) were calculated per 100 000 person-years
      (World Standard). Regression analysis was used to evaluate the annual change in
      the incidence of testicular cancer in each of the Nordic countries. The risk of
      testicular cancer in different professions was described based on NOCCA
      information and expressed as standardised incidence ratios (SIRs). RESULTS:
      During 2010-2014 the ASR for testicular cancer varied from 11.3 in Norway to 5.8
      in Finland. Until 1998, the incidence was highest in Denmark. There has not been
      an increase in Denmark and Iceland since the 1990s, whilst the incidence is still
      strongly increasing in Norway, Sweden, and Finland. There were no remarkable
      changes in the ratio of seminoma and non-seminoma incidences during the past 50
      years. There was no increase in the incidences in children and those of pension
      age. The highest significant excess risks of testicular seminoma were found in
      physicians (SIR 1.48, 95% confidence interval [CI] 1.07-1.99), artistic workers
      (SIR 1.47, 95% CI 1.06-1.99) and religious workers etc. (SIR 1.33, 95% CI 1.14
      1.56). The lowest SIRs of testicular seminoma were seen amongst cooks and
      stewards (SIR 0.56, 95% CI 0.29-0.98), and forestry workers (SIR 0.64, 95% CI
      0.47-0.86). The occupational category of administrators was the only one with a
      significantly elevated SIR for testicular non-seminoma (SIR 1.21, 95% CI 1.04
      1.42). The only SIRs significantly <1.0 were seen amongst engine operators (SIR
      0.60, 95% CI 0.41-0.84) and public safety workers (SIR 0.67, 95% CI 0.43-0.99).
      CONCLUSIONS: There have always been differences in the incidence of testicular
      cancer between the Nordic countries. There is also some divergence in the
      incidences in different age groups and in the trends of the incidence. The effect
      of occupation-related factors on incidence of testicular cancer is only moderate.
      Our study describes the differences, but provides no explanation for this
      variation.

PMID- 29460992
TI  - Formation Mechanism of Atmospheric Ammonium Bisulfate: Hydrogen-Bond-Promoted
      Nearly Barrierless Reactions of SO3 with NH3 and H2 O.
AB  - Particulate matter (PM) air pollution threatens the health of people and
      ecosystems worldwide. As the key component of PM, ammonium sulfate plays a
      critical role in the formation of aerosol particles; thus, there is an urgent
      need to know the detailed mechanisms for its formation in the atmosphere. Through
      a quantum chemistry study, we reveal a series of nearly barrierless reactions
      that may occur in clusters/droplets in the atmosphere leading to the formation of
      ammonium bisulfate (NH4 HSO4 ), the precursor of ammonium sulfate. In this
      mechanism, NH4 HSO4 is directly formed through one-step reactions of SO3 with H2
      O and NH3 promoted by surrounding molecule(s) that substantially lower the
      reaction activation barrier to ~0 kcal mol-1 . The promoters of these reactions
      are found to be various common atmospheric molecules, such as water, ammonia, and
      sulfuric acid, which can form relatively strong hydrogen bonds with the reaction
      center. Our results suggest many more similar pathways that can be facilitated by
      other ambient molecules. Due to its one-step and barrierless reaction
      characteristics and the great abundance of potential reactions, this mechanism
      has great implications on the formation of atmospheric ammonium sulfate as well
      as on the growth of aerosol particles.

PMID- 29460993
TI  - Direct Formation of C-C Triple-Bonded Structural Motifs by On-Surface
      Dehalogenative Homocouplings of Tribromomethyl-Substituted Arenes.
AB  - On-surface synthesis shows significant potential in constructing novel
      nanostructures/nanomaterials, which has been intensely studied in recent years.
      The formation of acetylenic scaffolds provides an important route to the
      fabrication of emerging carbon nanostructures, including carbyne, graphyne, and
      graphdiyne, which feature chemically vulnerable sp-hybridized carbon atoms.
      Herein, we designed and synthesized a tribromomethyl-substituted compound. By
      using a combination of high-resolution scanning tunneling microscopy, non-contact
      atomic force microscopy, and density functional theory calculations, we
      demonstrated that it is feasible to convert these compounds directly into C-C
      triple-bonded structural motifs by on-surface dehalogenative homocoupling
      reactions. Concurrently, sp3 -hybridized carbon atoms are converted into sp
      hybridized ones, that is, an alkyl group is transformed into an alkynyl moiety.
      Moreover, we achieved the formation of dimer structures, one-dimensional
      molecular wires, and two-dimensional molecular networks on Au(111) surfaces,
      which should inspire further studies towards two-dimensional graphyne structures.

PMID- 29460994
TI  - Sexual habits of men with ED who take phosphodiesterase 5 inhibitors: a survey
      conducted in 7 countries.
AB  - INTRODUCTION: Western cultural perceptions that favour spontaneous sex may create
      unrealistic expectations for erectile dysfunction (ED) treatment. Little is known
      about how users of phosphodiesterase type 5 inhibitors (PDE5Is) plan sexual
      activity and timing of their preactivity PDE5I ingestion. Because various PDE5Is
      vary in their duration of action and dosage regimen, this may be an important
      consideration in selecting the optimal agent for the ED patient. AIM: To better
      understand the sexual habits of PDE5I users. METHODS: Men from 7 countries
      (Brazil, China, Italy, Japan, Russia, Taiwan, Turkey) were screened online for
      age, self-reported comorbidities and ED medication use in the prior 3 months.
      After screening, eligible participants were asked to complete a 7-question, self
      administered online survey containing questions regarding sexual habits and
      behaviours. MAIN OUTCOME MEASURES: Survey questions focused primarily on advanced
      planning of sexual intercourse and timing of PDE5I ingestion but also addressed
      the frequency of sexual intercourse and ED medication use. RESULTS: Of the 1458
      respondents (response rate: 48%; median age: 48 years [interquartile range (IQR),
      44-55]), 83% always/sometimes planned a specific time for intercourse in advance;
      72% planned a specific time for sexual intercourse up to several hours in
      advance. Of respondents who planned in advance, more than half planned specific
      days of the week (55%) and times of the day (60%) for sexual intercourse. The
      time to sexual intercourse after dosing was <=1 hour for 70% and <=4 hours for
      96% of men. The median frequency of sexual intercourse was 6 times/month (IQR, 4
      10), with ED medication taken a median of 5 times/month (IQR, 3-8). CONCLUSIONS:
      Sexual activity is usually planned by ED medication users several hours in
      advance, and the vast majority are attempting activity within a short time after
      ingestion of the agent. These data should aid clinicians in the selection of the
      optimal PDE5I.

PMID- 29460996
TI  - Fluorine-Mediated Editing of a G-Quadruplex Folding Pathway.
AB  - A (3+1)-hybrid-type G-quadruplex was substituted within its central tetrad by a
      single 2'-fluoro-modified guanosine. Driven by the anti-favoring nucleoside
      analogue, a novel quadruplex fold with inversion of a single G-tract and
      conversion of a propeller loop into a lateral loop emerges. In addition, scalar
      couplings across hydrogen bonds demonstrate the formation of intra- and inter
      residual F???H8-C8 pseudo-hydrogen bonds within the modified quadruplexes.
      Alternative folding can be rationalized by the impact of fluorine on intermediate
      species on the basis of a kinetic partitioning mechanism. Apparently, chemical or
      other environmental perturbations are able to redirect folding of a quadruplex,
      possibly modulating its regulatory role in physiological processes.

PMID- 29460997
TI  - The impact of robotic surgery on quality of life, urinary and sexual function
      following total mesorectal excision for rectal cancer: a propensity score-matched
      analysis with laparoscopic surgery.
AB  - AIM: Quality of life (QoL) and functional outcomes are at risk of being impaired
      after rectal surgery, but there has been no large prospective study to thoroughly
      assess QoL according to surgical approach. We have investigated the impact of
      laparoscopic and robotic total mesorectal excision (TME) on QoL and functional
      outcomes. METHOD: Patients undergoing laparoscopic or robotic TME for rectal
      cancer between 2009 and 2013 were prospectively included in this questionnaire
      based survey of QoL together with variations in urinary and sexual function. A
      propensity score analysis was retrospectively conducted to compare outcomes
      between groups in a cohort matched 1:1 for age, sex, body mass index,
      preoperative chemoradiation status and tumour height. The survey was performed
      preoperatively and 3, 6 and 12 months after surgery. RESULTS: Global health
      status/QoL was similar between the two groups for 130 matched pairs, but the
      robotic group showed better role, emotional and social functioning and
      experienced less fatigue and financial difficulty. International Prostatic
      Symptom Scores in men increased postoperatively, with significantly less
      impairment in the robotic group at 6 months. These scores were comparable to
      preoperative scores at 6 months in the robotic group and at 12 months in the
      laparoscopic group. Of 48 sexually active men in each group, International Index
      of Erectile Function-5 scores decreased postoperatively, returning to
      preoperative levels at 6 months in the robotic group and at 12 months in the
      laparoscopic groups. CONCLUSION: The robotic approach for TME was associated with
      less impairment of urinary and sexual function; QoL was comparable to the
      laparoscopic approach.

PMID- 29460998
TI  - Corrigendum.

PMID- 29460999
TI  - PLA2R related primary membranous nephropathy in a hepatitis C positive patient.

PMID- 29461000
TI  - Corrigendum.

PMID- 29461001
TI  - Emphysematous cystitis and spontaneous sigmoid colon perforation in a patient
      with steroid-dependent nephrotic syndrome.

PMID- 29460995
TI  - The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration
      of spliceogenicity.
AB  - Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been
      demonstrated, its association with cancer risk remains controversial. In this
      study, we accurately quantified by real-time PCR and digital PCR (dPCR), the
      BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio
      for causality of the variant was estimated using genetic and clinical data, and
      its associated cancer risk was estimated by case-control analysis in 83,636
      individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed
      in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers
      (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele
      of approximately 20%. The posterior probability of pathogenicity was 7.44 * 10
      115 . There was neither evidence for increased risk of breast cancer (OR 1.03;
      95% CI 0.86-1.24) nor for a deleterious effect of the variant when co-occurring
      with pathogenic variants. Our data provide for the first time robust evidence of
      the nonpathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative
      transcript analyses together inform the threshold for the ratio between
      functional and altered BRCA2 isoforms compatible with normal cell function. These
      findings might be exploited to assess the relevance for cancer risk of other
      BRCA2 spliceogenic variants.

PMID- 29461002
TI  - A Case Report of Henoch-Schonlein Purpura and IgA Nephropathy Associated With
      Rivaroxaban.

PMID- 29461003
TI  - Multi-focal tuberculous osteomyelitis in a kidney transplant patient.

PMID- 29461005
TI  - Clinical findings and normative ocular data for free-living Anna's (Calypte anna)
      and Black-chinned (Archilochus alexandri) Hummingbirds.
AB  - OBJECTIVE: To estimate the prevalence of ocular disease and obtain normative
      ocular data for free-living hummingbirds. ANIMALS STUDIED: Two hundred and sixty
      three free-living, adult Hummingbirds from coastal and inland central California
      were studied, including Anna's (Calypte anna, n = 186) and Black-chinned
      (Archilochus alexandri; n = 77) hummingbirds. PROCEDURES: Slit lamp biomicroscopy
      and indirect ophthalmoscopy were performed on all individuals. Rebound tonometry,
      measurement of horizontal palpebral fissure length, and streak retinoscopy were
      performed on select individuals. Five conscious Anna's Hummingbirds underwent
      ocular imaging including fundus photography, digital slit lamp photography, and
      anterior segment and retinal optical coherence tomography. RESULTS: The
      prevalence of ocular disease in this population was 2.28%. Ocular imaging
      revealed a thin cornea, shallow anterior chamber, large lens, and a single
      central, deep convexiclivate fovea. Mean +/- SD intraocular pressure was 11.21 +/
      2.23 mm Hg. Mean +/- SD eyelid length was 2.59 +/- 0.19 mm. All eyes were
      emmetropic or mildly hyperopic with a mean (range) +/- SD refractive error of
      +0.32 (-0.25 to +1) +/- 0.33 diopters. CONCLUSIONS: Consistent with previous
      reports, these data suggest that hummingbirds have visual characteristics found
      in predatory and prey species, as well as a low prevalence of spontaneous ocular
      disease. This work provides a set of reference values and clinical findings that
      can be used in the future research on hummingbird vision and ocular disease. It
      also provides representative diagnostic images of normal birds and demonstrates
      that advanced ocular imaging can be performed on manually restrained hummingbirds
      without pharmacologic dilation.

PMID- 29461004
TI  - Effects of pre-analytical heat treatment in factor VIII (FVIII) inhibitor assays
      on FVIII antibody levels.
AB  - INTRODUCTION: The use of pre-analytical heat treatment (PHT) with the Nijmegen
      Bethesda assay (NBA) for inhibitors to factor VIII (FVIII) can remove/destroy
      infused or endogenous FVIII from patient plasma samples, allowing testing of
      recently infused patients with haemophilia. Two PHT methods have been described
      as follows: heating to 56 degrees C for 30 minutes and heating to 58 degrees C
      for 90 minutes. Data examining the effects of PHT on anti-FVIII IgG4 , the
      antibodies known to correlate most closely with the presence of FVIII inhibitors,
      are limited. AIM: To assess the effect of PHT on the levels of detectable anti
      FVIII IgG4 . METHODS: Nijmegen-Bethesda assay-positive specimens were incubated
      at 56, 58 or 60 degrees C for 90 minutes, and anti-FVIII IgG4 was measured by
      fluorescence immunoassay (FLI) at 30-minute intervals. The effects of PHT on the
      ability of recombinant FVIII (rFVIII) to inhibit detection of patient antibodies
      by FLI was also examined to assess the stability of rFVIII under the various PHT
      conditions tested. RESULTS: Levels of anti-FVIII IgG4 showed little change
      following incubations at 56 degrees C (mean 101% of original value at 30 minutes
      and 100% at 60 minutes) but decreased upon exposure to 58 degrees C (mean 85% at
      30 minutes and 66% at 60 minutes). In addition, heating to 56 degrees C
      effectively decreased the ability of rFVIII to block antibody binding compared to
      unheated rFVIII. CONCLUSION: The optimal temperature for PHT in the FVIII NBA is
      56 degrees C. Higher temperatures may lead to loss of inhibitory antibodies.

PMID- 29461006
TI  - Left ventricular geometric patterns in end-stage kidney disease: Determinants and
      course over time.
AB  - INTRODUCTION: While concentric left ventricular hypertrophy (cLVH) predominates
      in non-dialysis-dependent chronic kidney disease (CKD), eccentric left
      ventricular hypertrophy (eLVH) is most prevalent in dialysis-dependent CKD stage
      5 (CKD5D). In these patients, the risk of sudden death is 5* higher than in
      individuals with cLVH. Currently, it is unknown which factors determine left
      ventricular (LV) geometry and how it changes over time in CKD5D. METHODS: Data
      from participants of the CONvective TRAnsport Study who underwent serial
      transthoracic echocardiography were used. Based on left ventricular mass (LVM)
      and relative wall thickness (RWT), 4 types of left ventricular geometry were
      distinguished: normal, concentric remodeling, eLVH, and cLVH. Determinants of
      eLVH were assessed with logistic regression. Left ventricular geometry of
      patients who died and survived were compared. Long-term changes in RWT and LVM
      were evaluated with a linear mixed model. FINDINGS: Three hundred twenty-two
      patients (63.1 +/- 13.3 years) were included. At baseline, LVH was present in 71%
      (cLVH: 27%; eLVH: 44%). Prior cardiovascular disease (CVD) was positively
      associated with eLVH and beta-blocker use inversely. None of the putative volume
      parameters showed any relationship with eLVH. Although eLVH was most prevalent in
      non-survivors, the distribution of left ventricular geometry did not vary over
      time. DISCUSSION: The finding that previous CVD was positively associated with
      eLVH may result from the permanent high cardiac output and the strong tendency
      for aortic valve calcification in this group of long-term hemodialysis patients,
      who suffer generally also from chronic anemia and various other metabolic
      derangements. No association was found between eLVH and parameters of fluid
      balance. The distribution of left ventricular geometry did not alter over time.
      The assumption that LV geometry worsens over time in susceptible individuals, who
      then suffer from a high risk of dying, may explain these findings.

PMID- 29461007
TI  - Radio-cephalic arteriovenous fistula recovered with drainage through the brachial
      vein.
AB  - Dysfunction of arteriovenous access for hemodialysis is a challenge for the
      vascular surgeon. Some patients have complex vascular access with problems that
      are difficult to solve. Careful analysis of the vascular network with ultrasound
      and dissection of the veins during surgery can help to identify the best option
      for each access. We introduce and discuss the case of creation of a radio
      cephalic fistula with outflow into the brachial vein in 64-year-old hemodialysis
      male patient. This technique enables extending fistula patency, arterializing the
      brachial vein, and improves cost efficiency.

PMID- 29461008
TI  - Propofol exposure during early gestation impairs learning and memory in rat
      offspring by inhibiting the acetylation of histone.
AB  - Propofol is widely used in clinical practice, including non-obstetric surgery in
      pregnant women. Previously, we found that propofol anaesthesia in maternal rats
      during the third trimester (E18) caused learning and memory impairment to the
      offspring rats, but how about the exposure during early pregnancy and the
      underlying mechanisms? Histone acetylation plays an important role in synaptic
      plasticity. In this study, propofol was administered to the pregnant rats in the
      early pregnancy (E7). The learning and memory function of the offspring were
      tested by Morris water maze (MWM) test on post-natal day 30. Two hours before
      each MWM trial, histone deacetylase 2 (HDAC2) inhibitor, suberoylanilide
      hydroxamic acid (SAHA), Senegenin (SEN, traditional Chinese medicine),
      hippyragranin (HGN) antisense oligonucleotide (HGNA) or vehicle were given to the
      offspring. The protein levels of HDAC2, acetylated histone 3 (H3) and 4 (H4),
      cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), N
      methyl-D-aspartate receptor (NMDAR) 2 subunit B (NR2B), HGN and synaptophysin in
      offspring's hippocampus were determined by Western blot or immunofluorescence
      test. It was discovered that infusion with propofol in maternal rats on E7 leads
      to impairment of learning and memory in offspring, increased the protein levels
      of HDAC2 and HGN, decreased the levels of acetylated H3 and H4 and phosphorylated
      CREB, NR2B and synaptophysin. HDAC2 inhibitor SAHA, Senegenin or HGN antisense
      oligonucleotide reversed all the changes. Thus, present results indicate exposure
      to propofol during the early gestation impairs offspring's learning and memory
      via inhibiting histone acetylation. SAHA, Senegenin and HGN antisense
      oligonucleotide might have therapeutic value for the adverse effect of propofol.

PMID- 29461009
TI  - Metabolomic responses to lumacaftor/ivacaftor in cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) is a life-limiting disease caused by a defect in
      the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
      Lumacaftor/Ivacaftor is a novel CFTR modulator approved for patients that are
      homozygous for Phe508del CFTR, but its clinical effectiveness varies amongst
      patients, making it difficult to determine clinical responders. Therefore,
      identifying biochemical biomarkers associated with drug response are clinically
      important for follow-up studies. METHODS: Serum metabolomics was performed on
      twenty patients with CF pre- and 6-month post-Lumacaftor/Ivacaftor response via
      Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC
      MS/MS). Correlation with clinical variables was performed. RESULTS: Metabolomics
      analysis demonstrated 188 differentially regulated metabolites between patients
      pre- and post-Lumacaftor/Ivacaftor initiation, with a predominance of lipid and
      amino acid alterations. The top 30 metabolites were able to differentiate pre-
      and post-Lumacaftor/Ivacaftor status in greater than 90% of patients via a random
      forest confusion matrix. Alterations in bile acids, phospholipids, and bacteria
      associated metabolites were the predominant changes associated with drug
      response. Importantly, changes in metabolic patterns were associated with
      clinical responders. CONCLUSIONS: Selected key lipid and amino acid metabolic
      pathways were significantly affected by Lumacaftor/Ivacaftor initiation and
      similar pathways were affected in clinical responders. Targeted metabolomics may
      provide useful and relevant biomarkers of CFTR modulator responses.

PMID- 29461010
TI  - Genetic and phylogenetic analysis of reemerged novel Seneca Valley virus strains
      in Guangdong province, 2017.
AB  - From June to July 2017, six Seneca Valley virus (SVV) strains were isolated from
      swine herds exhibiting SVV-associated porcine idiopathic vesicular disease (PIVD)
      in Guangdong province, China. Complete genomic sequences of these six newly
      identified strains were genetically and phylogenetically analysed. The results
      revealed that these six SVV strains were genetically closely related to
      USA/GBI29/2015 and notably distinct from all previous Chinese strains, indicating
      the reemergence of new SVV strains in Guangdong province.

PMID- 29461011
TI  - Spinocerebellar ataxia type 2 presenting with rapidly progressing muscle weakness
      and muscular atrophy.

PMID- 29461012
TI  - Graft healing after extensive necrotizing fasciitis of the leg in an 85-year-old
      man.

PMID- 29461013
TI  - Improved effect of ultra-pure soft water on skin water content in older adults.

PMID- 29461014
TI  - Cyproterone acetate as a treatment for moderate-to-severe inappropriate sexual
      behavior in dementia.

PMID- 29461015
TI  - Optimal range of injection rates for a lymphatic drug delivery system.
AB  - The lymphatic drug delivery system (LDDS) is a new technique that permits the
      injection of drugs into a sentinel lymph node (SLN) at an early stage of tumor
      metastasis, thereby treating metastasis in the SLN and its secondary lymph nodes
      (LNs). The quantity of drug required for a LDDS is much smaller than that needed
      for systemic chemotherapy. However, the relationship between the rate of drug
      injection into a SLN and the amount of drug reaching the secondary LNs has not
      been investigated. In this study, we used an MXH10/Mo-lpr/lpr mouse model to show
      that the optimal rate for the injection of a fluorescent dye by a LDDS was 10 to
      80 MUL/min. An injection rate of 10 to 80 MUL/min was able to fill the downstream
      LN. However, an injection rate of 100 MUL/min drove the fluorescent dye into the
      efferent lymphatic vessels and thoracoepigastric vein, decreasing the amount of
      dye retained in the downstream LN. Bolus injection (defined as an injection rate
      of 2400 MUL/min) was unable to deliver fluorescent dye into the downstream LN.
      These results agree with the impulse values calculated from the injection
      pressures in the upstream LN. We anticipate that our findings will facilitate the
      development of a LDDS for use in the clinic.

PMID- 29461016
TI  - Postdialysis recovery time is extended in patients with greater self-reported
      depression screening questionnaire scores.
AB  - INTRODUCTION: Most patients take time to recover after a hemodialysis (HD)
      session. It has been suggested that recovery time is associated with
      intradialytic hypotension and rapid solute clearances. Other studies have
      reported a linkage to depression. We investigated the association between
      recovery time and intradialytic hypotension and depression. METHODS: In five UK
      HD units, we screened for depressive symptoms using the Beck depression inventory
      II, Patient Health Questionnaire, and recorded sessional blood pressures and
      Kt/Vurea. FINDINGS: Seven hundred and one HD patients were studied; 63.6% male,
      mean age 64.1 +/- 16.6 years, 33.5% diabetic. About 24.1% recovered in <1 hour,
      27% 1-4 hours, 15.4% 4-8 hours, 10.7% 8-12 hours, and 22.8% after 12 hours.
      Systolic blood pressure fell by >=20 mmHg in 30.9% postdialysis, and to <100 mmHg
      in 7.6%. In multivariate analysis, patients with recovery times >1 hour were more
      likely to be female, have high self-reported Beck depression inventory-II scores,
      a past medical history of depression, and be living without a partner. Longer
      recovery times were also associated with very low postdialysis systolic blood
      pressures (<100 mmHg), and higher body weight. However, the model predicted only
      18% of the variation in recovery times. We found no association between recovery
      times and short-term mortality risk. DISCUSSION: Prolonged postdialysis recovery
      times are associated with higher self-reported depression scores, and very low
      postdialysis blood pressure. Future studies investigating changes in dialysis
      practice and recovery times will need to target strategies to prevent
      intradialytic hypotension and adjust for patient psychological status.

PMID- 29461017
TI  - Medication adherence in pediatric asthma: A systematic review of the literature.
AB  - OBJECTIVE: To provide a systematic review of correlates of adherence to inhaled
      corticosteroids (ICS) in pediatric asthma across the individual, family,
      community, and healthcare system domains. METHODS: Articles assessing medication
      adherence in pediatric asthma published from 1997 to 2016 were identified using
      PsychINFO, Medline, and CINAHL. Search terms included asthma, compliance, self
      management, adherence, child, and youth. Search results were limited to articles:
      1) published in the US; 2) using a pediatric population (0-25 years old); and 3)
      presenting original data related to ICS adherence. Correlates of adherence were
      categorized according to the domains of the Pediatric Self-Management Model. Each
      article was evaluated for study quality. RESULTS: Seventy-nine articles were
      included in the review. Family-level correlates were most commonly reported (N =
      51) and included socioeconomic status, race/ethnicity, health behaviors, and
      asthma knowledge. Individual-level correlates were second-most common (N = 37),
      with age being the most frequently identified negative correlate of adherence.
      Health care system correlates (N = 24) included enhanced asthma care and patient
      provider communication. Few studies (N = 10) examined community correlates of
      adherence. Overall study quality was moderate, with few quantitative articles
      (26.38%) and qualitative articles (21.4%) referencing a theoretical basis for
      their studies. CONCLUSIONS: All Pediatric Self-Management Model domains were
      correlated with youth adherence, which suggests medication adherence is
      influenced across multiple systems; however, most studies assessed adherence
      correlates within a single domain. Future research is needed that cuts across
      multiple domains to advance understanding of determinants of adherence.

PMID- 29461018
TI  - Analysis of new psychoactive substances in human urine by ultra-high performance
      supercritical fluid and liquid chromatography: Validation and comparison.
AB  - New psychoactive substances represent serious social and health problem as tens
      of new compounds are detected in Europe annually. They often show structural
      proximity or even isomerism, which complicates their analysis. Two methods based
      on ultra high performance supercritical fluid chromatography and ultra high
      performance liquid chromatography with mass spectrometric detection were
      validated and compared. A simple dilute-filter-and-shoot protocol utilizing
      propan-2-ol or methanol for supercritical fluid or liquid chromatography,
      respectively, was proposed to detect and quantify 15 cathinones and
      phenethylamines in human urine. Both methods offered fast separation (<3 min) and
      short total analysis time. Precision was well <15% with a few exceptions in
      liquid chromatography. Limits of detection in urine ranged from 0.01 to 2.3
      ng/mL, except for cathinone (5 ng/mL) in supercritical fluid chromatography.
      Nevertheless, this technique distinguished all analytes including four pairs of
      isomers, while liquid chromatography was unable to resolve fluoromethcathinone
      regioisomers. Concerning matrix effects and recoveries, supercritical fluid
      chromatography produced more uniform results for different compounds and at
      different concentration levels. This work demonstrates the performance and
      reliability of supercritical fluid chromatography and corroborates its
      applicability as an alternative tool for analysis of new psychoactive substances
      in biological matrixes.

PMID- 29461019
TI  - Serum vitamin D profile of Nigerian children with asthma: Association with asthma
      severity and control.
AB  - OBJECTIVE: Childhood asthma is a chronic inflammatory airway disorder with
      increasing prevalence even in Africa. Vitamin D, with anti-inflammatory and
      immune-modulatory properties, may have effects on the severity and level of
      symptoms control in childhood asthma. We aimed to assess the serum vitamin D
      levels in children with asthma as related to disease severity and control in a
      tropical region. METHODS: A hospital based comparative cross sectional study was
      conducted in western Nigeria. Serum vitamin D (25-OH-D) levels of all the
      children, assayed using high-performance liquid chromatography (HPLC), were
      compared to the various disease severity and levels of asthma control as well as
      between the asthmatic and non-asthmatic children. RESULTS: A total of 206
      children (103 asthmatics and 103 non-asthmatics) were recruited with a mean (SD)
      age of 6.6 (3.7) years. The majority (82.5%) of the children with asthma had mild
      intermittent form, 63.1% had well controlled symptoms while 33.0% and 3.9% had
      partly controlled and uncontrolled symptoms, respectively. None of the children
      were deficient in vitamin D. The mean (SD) serum vitamin D levels of the children
      with asthma (49.2 [7.2] ng/mL) was significantly lower than those without asthma
      (51.2 [6.9] ng/mL, P = 0.043). Varying degrees of asthma severity and levels of
      symptoms control were not affected by serum vitamin D levels. CONCLUSION:
      Children with asthma in Nigeria had marginally but significantly lower mean serum
      vitamin D levels when compared with their counterparts without asthma. However,
      serum vitamin D level does not seem to be associated with childhood asthma
      severity and control in these children with normal serum vitamin D levels.

PMID- 29461020
TI  - Porphyromonas gingivalis: the gift of community involvement.

PMID- 29461021
TI  - Respiratory syncytial virus is an "opportunistic" killer.
AB  - Respiratory syncytial virus (RSV), responsible for more than three million yearly
      hospitalizations and up to 118 000 deaths in children under 5 years, is the
      leading pulmonary cause of death for this age group that lacks a licensed
      vaccine. Ninety-nine percent of deaths due to the virus occur in developing
      countries. In-hospital RSV fatalities affect previously healthy term infants in
      association with bacterial sepsis, clinically significant pneumothoraxes and, to
      a lesser extent, comorbid conditions. Community deaths affect low-income children
      from socially vulnerable families and appear to be as frequent as inpatient
      fatalities. In industrialized countries, RSV deaths occur almost exclusively in
      children with premorbid conditions. In a sense, RSV is an "opportunistic" killer.
      It needs a synergistic premorbid, medical practice-related, infectious, or social
      co-factor to cause a fatal outcome. But while the complex problems associated
      with these co-factors await solutions, candidate vaccines, long-lived monoclonal
      antibodies and antivirals against RSV are under clinical evaluation. It seems
      reasonable to predict that the landscape of RSV infections will look different in
      the next decade.

PMID- 29461022
TI  - Medicare, Medicaid, and Children's Health Insurance Programs: Announcement of the
      Extension of Temporary Moratoria on Enrollment of Part B Non-Emergency Ground
      Ambulance Suppliers and Home Health Agencies in Designated Geographic Locations.
      Extension of temporary moratoria.
AB  - This document announces the extension of statewide temporary moratoria on the
      enrollment of new Medicare Part B non-emergency ground ambulance providers and
      suppliers and Medicare home health agencies, subunits, and branch locations in
      Florida, Illinois, Michigan, Texas, Pennsylvania, and New Jersey, as applicable,
      to prevent and combat fraud, waste, and abuse. This extension also applies to the
      enrollment of new non-emergency ground ambulance suppliers and home health
      agencies, subunits, and branch locations in Medicaid and the Children's Health
      Insurance Program in those states. For purposes of these moratoria, providers
      that were participating as network providers in one or more Medicaid managed care
      organizations prior to January 1, 2018 will not be considered "newly enrolling"
      when they are required to enroll with the State Medicaid agency pursuant to a new
      statutory requirement, and thus will not be subject to the moratoria.

PMID- 29461023
TI  - Schedules of Controlled Substances: Extension of Temporary Placement of MAB
      CHMINACA in Schedule I of theControlled Substances Act. Temporary rule; temporary
      scheduling order; extension.
AB  - The Administrator of the Drug Enforcement Administration is issuing this
      temporary scheduling order to extend the temporary schedule I status of a
      synthetic cannabinoid, N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1
      (cyclohexylmethyl)-1H-indazole-3-carboxamide (other names: MAB-CHMINACA; ADB
      CHMINACA), including its optical, positional and geometric isomers, salts, and
      salts of isomers. The schedule I status of MAB-CHMINACA currently is in effect
      through February 4, 2018. This temporary order will extend the temporary
      scheduling of MAB-CHMINACA for one year, or until the permanent scheduling action
      for this substance is completed, whichever occurs first.

PMID- 29461024
TI  - Stricken: the Need for Positive Statutory Law to Prevent Discriminatory
      Peremptory Strikes of Disabled Jurors.

PMID- 29461025
TI  - Older Californians and the Mental Health Services Act: Is an Older Adult System
      of Care Supported?
AB  - This policy brief summarizes findings from the first study to evaluate how
      California's public mental health delivery system has served older adults (60
      years of age and over) since the passage of the Mental Health Services Act (MHSA)
      in 2004. Study findings indicate that there are unmet needs among older adults
      with mental illness in the public mental health delivery system. There are
      deficits in the involvement of older adults in the required MHSA planning
      processes and in outreach and service delivery, workforce development, and
      outcomes measurement and reporting. There is also evidence of promising programs
      and strategies that counties have advanced to address these deficits.
      Recommendations for improving mental health services for older adults include
      designating a distinct administrative and leadership structure for older adult
      services in each county; enhancing older adult outreach and documentation of
      unmet need; promoting standardized geriatric training of providers; instituting
      standardized data-reporting requirements; and increasing service integration
      efforts, especially between medical, behavioral health, aging, and substance use
      disorder services.

PMID- 29461026
TI  - Mental Health Services for Older Adults: Creating a System That Tells the Story.
AB  - In 2004, voters in California approved Proposition 63 for passage of the Mental
      Health Services Act (MHSA). From thattime until 2014, over $13 billion in the
      state's tax revenue was allocated for public mental health services. There is
      very little information available to answer critical questions such as these: How
      much of this amount was spent in the interests of older adult mental health? What
      benefits were gained from services delivered to older adults? This policy brief
      promotes recommendations for specific age-relevant indicator utilization and for
      an expanded system of uniform and transparent data for all types of MHSA-funded
      programs. These two policy directions are necessary in order to document the
      older adult mental health care services provided and to track outcomes at the
      state level for MHSA programs. A third recommendation centers on assuring that
      the mental health workforce is prepared to utilize and report age-relevant data
      indicators.

PMID- 29461027
TI  - [Effect of forest management on the herpetofauna of a temperate forest of western
      Oaxaca, Mexico].
AB  - The development of silvicultural techniques has as main objective to maximize the
      production of timber, whereas at the same time minimize the impact generated
      during and after forest intervention in the local diversity. However, these
      activities change local climate, and this, in turn, alter the composition of
      natural communities. The effect of these changes may be greater in those
      taxonomic groups with high sensitivity to habitat disturbance, such as amphibians
      and reptiles, which are the unique terrestrial ectothermic vertebrates. The
      present study aims to know the differences in diversity of amphibians and
      reptiles in a temperate forest under two silvicultural treatments, one of low and
      the other of high intensity, as well as from one, five and ten years of
      regeneration since the last logging event, Sierra Sur of Oaxaca, Mexico. Records
      of 21 species of herpetofauna (six amphibians and 15 reptiles) were obtained. The
      total species richness was similar in both treatments; however, the composition
      varied between sites with different recovery times. Higher abundance of amphibian
      was presented on sites with the low-intensity treatment, while reptiles were more
      abundant at sites with intensive treatment. Compared to a mature forest without
      management, sites with intensive treatment have more rare species, although the
      values of true diversity of amphibians were similar between treatments with
      different intensities, while for reptiles sites under treatment showed less
      diversity that unmanaged site: 33 % for intensive treatment and 28 % at sites
      with low intensity with respect to one control site. Complementary Analysis
      showed a difference of 86 % between the compositions of species in sites with
      intensive treatment. The treatment intensity was associated with an increase in
      the number of species, but the way they respond to changes in habitat depends
      largely on the population characteristics of each species and its ability to
      adapt to new conditions.

PMID- 29461028
TI  - Dung removal by dung beetles (Coleoptera: Scarabaeidae) and macrocyclic lactone
      use on cattle ranches of Yucatan, Mexico.
AB  - The expanded use of macrocyclic lactones (ML) to treat endo- and ectoparasites in
      cattle in tropical regions, can reduce dung beetle populations, and thus
      interrupt the dung removal process in cattle pasture ecosystems. During the
      reproductive period (the rainy season) of two functional groups of dung beetles
      (paracoprid and telocoprid Scarabaeinae), we compared dung removal amount in
      ranches where ML are and are not used in Yucatan, Mexico, through exclusion traps
      baited with 500 g of ML-free cow dung. On each ranch, two transects (separated by
      500 m) with six traps each, were set up for 24 hours. After this time, all the
      dung remnants in each trap were obtained and weighed in order to record the dung
      removal. Results showed that dung removal amounts were similar in ranches with
      and without ML use. Dung beetles removed 40.1 % of all cow dung weighed.
      Paracoprids removed 87.46 % and telocoprids 12.54 % of all the dung that was
      removed. Our results indicated that the ecological function of dung beetles in
      the pastures studied, does not seem to be affected by the ML use, and that
      paracoprid species removed most of the dung. For both types of ranch, further
      studies that take into account the population dynamics and movement of the most
      important dung beetle species in the region are required, coupled with laboratory
      studies evaluating the effect of ML on their reproductive success. This could
      give some light on the effect of ML on the ecological function of this important
      insect group in the sustainability of cattle production systems.

PMID- 29461029
TI  - Molecular Sieve Induced Solution Growth of Li2O2 in the Li-O2 Battery with
      Largely Enhanced Discharge Capacity.
AB  - The formation of the insulated film-like discharge products (Li2O2) on the
      surface of the carbon cathode gradually hinders the oxygen reduction reaction
      (ORR) process, which usually leads to the premature death of the Li-O2 battery.
      In this work, by introducing the molecular sieve powder into the ether
      electrolyte, the Li-O2 battery exhibits a largely improved discharge capacity (63
      times) compared with the one in the absence of this inorganic oxide additive.
      Meanwhile, XRD and SEM results qualitatively demonstrate the generation of the
      toroid Li2O2 as the dominated discharge products, and the chemical titration
      quantifies a higher yield of the Li2O2 with the presence of the molecular sieve
      additive. The addition of the molecular sieve controls the amount of the free
      water in the electrolyte, which distinguishes the effect of the molecular sieve
      and the free water on the discharge process. Hence, a possible mechanism has been
      proposed that the adsorption of the molecular sieves toward the soluble lithium
      superoxides improves the disproportionation of the lithium superoxides and
      consequently enhances the solution-growth of the lithium peroxides in the low
      donor number ether electrolyte. In general, the application of the molecular
      sieve triggers further studies concerning the improvement of the discharge
      performance in the Li-O2 battery by adding the inorganic additives.

PMID- 29461030
TI  - Synthesis and Characterization of CuFe2O4 Nano/Submicron Wire-Carbon Nanotube
      Composites as Binder-free Anodes for Li-Ion Batteries.
AB  - A series of one-dimensional CuFe2O4 (CFO) nano/submicron wires possessing
      different diameters, crystal phases, and crystal sizes have been successfully
      generated using a facile template-assisted coprecipitation reaction at room
      temperature, followed by a short postannealing process. The diameter and crystal
      structure of the resulting CuFe2O4 (CFO) wires were judiciously tuned by varying
      the pore size of the template and the postannealing temperature, respectively.
      Carbon nanotubes (CNTs) were incorporated to generate CFO-CNT binder-free anodes,
      and multiple characterization techniques were employed with the goal of
      delineating the relationships between electrochemical behavior and the properties
      of both the CFO wires (crystal phase, wire diameter, crystal size) and the
      electrode architecture (binder-free vs conventionally prepared approaches). The
      study reveals several notable findings. First, the crystal phase (cubic or
      tetragonal) did not influence the electrochemical behavior in this CFO system.
      Second, regarding crystallite size and wire diameter, CFO wires with larger
      crystallite sizes exhibit improved cycling stability, whereas wires possessing
      smaller diameters exhibit higher capacities. Finally, the electrochemical
      behavior is strongly influenced by the electrode architecture, with CFO-CNT
      binder-free electrodes demonstrating significantly higher capacities and cycling
      stability compared to conventionally prepared coatings. The mechanism(s)
      associated with the high capacities under low current density but limited
      electrochemical reversibility of CFO electrodes under high current density were
      probed via X-ray absorption spectroscopy mapping with submicron spatial
      resolution for the first time. Results suggest that the capacity of the binder
      free electrodes under high rate is limited by the irreversible formation of Cu0,
      as well as limited reduction of Fe3+ to Fe2+, not Fe0. The results (1) shed
      fundamental insight into the reversibility of CuFe2O4 materials cycled at high
      current density and (2) demonstrate that a synergistic effort to control both
      active material morphology and electrode architecture is an effective strategy
      for optimizing electrochemical behavior.

PMID- 29461031
TI  - Redox Additive-Improved Electrochemically and Structurally Robust Binder-Free
      Nickel Pyrophosphate Nanorods as Superior Cathode for Hybrid Supercapacitors.
AB  - For several decades, one of the great challenges for constructing a high-energy
      supercapacitor has been designing electrode materials with high performance.
      Herein, we report for the first time to our knowledge a novel hybrid
      supercapacitor composed of battery-type nickel pyrophosphate one-dimensional (1D)
      nanorods and capacitive-type N-doped reduced graphene oxide as the cathode and
      anode, respectively, in an aqueous redox-added electrolyte. More importantly, ex
      situ microscopic images of the nickel pyrophosphate 1D nanorods revealed that the
      presence of the battery-type redox additive enhanced the charge storage capacity
      and cycling life as a result of the microstructure stability. The nickel
      pyrophosphate 1D nanorods exhibited their maximum specific capacitance (8120 mF
      cm-2 at 5 mV s-1) and energy density (0.22 mWh cm-2 at a power density of 1.375
      mW cm-2) in 1 M KOH + 75 mg K3[Fe(CN)6] electrolyte. On the other side, the N
      doped reduced graphene oxide delivered an excellent electrochemical performance,
      demonstrating that it was an appropriate anode. A hybrid supercapacitor showed a
      high specific capacitance (224 F g-1 at a current density of 1 A g-1) and high
      energy density (70 Wh kg-1 at a power density of 750 W kg-1), as well as a long
      cycle life (a Coulombic efficiency of 96% over 5000 cycles), which was a higher
      performance than most of those in recent reports. Our results suggested that the
      materials and redox additive in this novel design hold great promise for
      potential applications in a next-generation hybrid supercapacitor.

PMID- 29461033
TI  - >1000-Fold Lifetime Extension of a Nickel Electromechanical Contact Device via
      Graphene.
AB  - Micro-/nano-electromechanical (M/NEM) switches have received significant
      attention as promising switching devices for a wide range of applications such as
      computing, radio frequency communication, and power gating devices. However,
      M/NEM switches still suffer from unacceptably low reliability because of
      irreversible degradation at the contacting interfaces, hindering adoption in
      practical applications and further development. Here, we evaluate and verify
      graphene as a contact material for reliability-enhanced M/NEM switching devices.
      Atomic force microscopy experiments and quantum mechanics calculations reveal
      that energy-efficient mechanical contact-separation characteristics are achieved
      when a few layers of graphene are used as a contact material on a nickel surface,
      reducing the energy dissipation by 96.6% relative to that of a bare nickel
      surface. Importantly, graphene displays almost elastic contact-separation,
      indicating that little atomic-scale wear, including plastic deformation,
      fracture, and atomic attrition, is generated. We also develop a feasible
      fabrication method to demonstrate a MEM switch, which has high-quality graphene
      as the contact material, and verify that the devices with graphene show
      mechanically stable and elastic-like contact properties, consistent with our
      nanoscale contact experiment. The graphene coating extends the switch lifetime
      >103 times under hot switching conditions.

PMID- 29461032
TI  - Novel Cyclosilazane-Type Silicon Precursor and Two-Step Plasma for Plasma
      Enhanced Atomic Layer Deposition of Silicon Nitride.
AB  - We designed cyclosilazane-type silicon precursors and proposed a three-step
      plasma-enhanced atomic layer deposition (PEALD) process to prepare silicon
      nitride films with high quality and excellent step coverage. The cyclosilazane
      type precursor, 1,3-di-isopropylamino-2,4-dimethylcyclosilazane (CSN-2), has a
      closed ring structure for good thermal stability and high reactivity. CSN-2
      showed thermal stability up to 450  degrees C and a sufficient vapor pressure of
      4 Torr at 60  degrees C. The energy for the chemisorption of CSN-2 on the
      undercoordinated silicon nitride surface as calculated by density functional
      theory method was -7.38 eV. The PEALD process window was between 200 and 500 
      degrees C, with a growth rate of 0.43 A/cycle. The best film quality was obtained
      at 500  degrees C, with hydrogen impurity of ~7 atom %, oxygen impurity less than
      2 atom %, low wet etching rate, and excellent step coverage of ~95%. At 300 
      degrees C and lower temperatures, the wet etching rate was high especially at the
      lower sidewall of the trench pattern. We introduced the three-step PEALD process
      to improve the film quality and the step coverage on the lower sidewall. The
      sequence of the three-step PEALD process consists of the CSN-2 feeding step, the
      NH3/N2 plasma step, and the N2 plasma step. The H radicals in NH3/N2 plasma
      efficiently remove the ligands from the precursor, and the N2 plasma after the
      NH3 plasma removes the surface hydrogen atoms to activate the adsorption of the
      precursor. The films deposited at 300  degrees C using the novel precursor and
      the three-step PEALD process showed a significantly improved step coverage of
      ~95% and an excellent wet etching resistance at the lower sidewall, which is only
      twice as high as that of the blanket film prepared by low-pressure chemical vapor
      deposition.

PMID- 29461034
TI  - Inhibition of HIV Fusion by Small Molecule Agonists through Efficacy-Engineering
      of CXCR4.
AB  - CXC chemokine receptor 4 (CXCR4) is involved in multiple physiological and
      pathological processes, notably as a coreceptor for human immunodeficiency virus
      (HIV) cell entry. Its broad expression pattern and vital biological importance
      make CXCR4 a troublesome drug target, as disruption of the interaction with its
      endogenous ligand, CXC chemokine ligand 12 (CXCL12), has severe consequences. In
      fact, only one CXCR4 drug, the bicyclam antagonist and HIV entry inhibitor
      AMD3100 (Plerixafor/Mozobil), has been approved for clinical use, however only
      for stem cell mobilization-a consequence of CXCR4 antagonism. Here, we report the
      engineering of an efficacy switch mutation in CXCR4-F292A7.43 in the middle of
      transmembrane helix 7-that converted the antagonists AMD3100 and AMD11070 into
      partial agonists. As agonists on F292A CXCR4, AMD3100 and AMD11070 were less
      disruptive to CXCR4 signaling while they remained efficient inhibitors of HIV
      fusion. This demonstrates that small molecule CXCR4 agonists can have a
      therapeutic potential as HIV entry inhibitors.

PMID- 29461036
TI  - Patterning Multi-Nanostructured Poly(l-lactic acid) Fibrous Matrices to
      Manipulate Biomolecule Distribution and Functions.
AB  - Precise manipulation of biomolecule distribution and functions via biomolecule
      matrix interaction is very important and challenging for tissue engineering and
      regenerative medicine. As a well-known biomimetic matrix, electrospun fibers
      often lack the unique spatial complexity compared to their natural counterparts
      in vivo and thus cannot deliver fully the regulatory cues to biomolecules. In
      this paper, we report a facile and reliable method to fabricate micro- and
      nanostructured poly(l-lactic acid) (PLLA) fibrous matrices with spatial
      complexity by a combination of advanced electrospinning and agarose hydrogel
      stamp-based micropatterning. Specifically, advanced electrospinning is used to
      construct multi-nanostructures of fibrous matrices while solvent-loaded agarose
      hydrogel stamps are used to create microstructures. Compared with other methods,
      our method shows extreme simplicity and flexibility originated from the mono
      /multi-spinneret conversion and limitless micropatterns of agarose hydrogel
      stamps. Three types of PLLA fibrous matrices including patterned nano-Ag/PLLA
      hybrid fibers, patterned bicompartment polyethylene terephthalate/PLLA fibers,
      and patterned hollow PLLA fibers are fabricated and their capability to
      manipulate biomolecule distribution and functions, that is, bacterial
      distribution and antibacterial performance, cell patterning and
      adhesion/spreading behaviors, and protein adsorption and delivery, is
      demonstrated in detail. The method described in our paper provides a powerful
      tool to restore spatial complexity in biomimetic matrices and would have
      promising applications in the field of biomedical engineering.

PMID- 29461035
TI  - Heparin-Eluting Electrospun Nanofiber Yarns for Antithrombotic Vascular Sutures.
AB  - The surgical connection of blood vessels, anastomosis, is a critical procedure in
      many reparative, transplantation, and reconstructive surgical procedures.
      However, effective restoration of circulation is complicated by pathological
      clotting (thrombosis) or progressive occlusion due to excess cell proliferation
      that often leads to additional surgeries and increases morbidity and mortality
      risk for patients. Pharmaceutical agents have been tested to prevent these
      complications, but many have unacceptable systemic side effects. Therefore, an
      alternative approach to deliver these drugs at the site of injury in a controlled
      manner is necessary. The objective of this study was to develop electrospun
      nanofibers composed of polyester poly(lactide- co-glycolide) (PLGA),
      poly(ethylene oxide) (PEO), and positively charged copolymer, poly(lactide- co
      glycolide)- graft-polyethylenimine (PgP) for electrostatic binding and release of
      heparin for application as an antithrombotic microvascular suture. PgP was
      synthesized with different coupling ratios between PLGA and branched
      polyethylenimine (bPEI) to obtain PgP1 (~1 PLGA grafted to 1 bPEI) and PgP3.7
      (~3.7 PLGA grafted to 1 bPEI). Nanofiber yarns (PLGA/PEO/PgP1 and
      PLGA/PEO/PgP3.7) were fabricated by electrospinning. Heparin immobilization on
      the positively charged nanofiber yarns was visualized using fluorescein
      conjugated heparin (F-Hep), and the amount of immobilized F-Hep was higher on
      both PLGA/PEO/PgP3.7 and PLGA/PEO/PgP1 than yarns without PgP (PLGA/PEO). We also
      found that F-Hep was released from both PgP-containing yarns in a sustained
      manner over 20 days, while over 60% of F-Hep was released within 4 h from
      PLGA/PEO. Finally, we observed that heparin-eluting nanofiber yarns with both
      PgP1 and PgP3.7 showed significantly longer clotting times than nanofiber yarns
      without PgP. The clotting time of PLGA/PEO/PgP3.7 was not significantly different
      than that of free heparin (0.5 MUg/mL). These results show that heparin-eluting
      electrospun nanofiber yarns may offer a basis for the development of
      microvascular sutures with anticoagulant activity.

PMID- 29461037
TI  - Thermosensitive Metal Chelation Dual-Template Epitope Imprinting Polymer Using
      Distillation-Precipitation Polymerization for Simultaneous Recognition of Human
      Serum Albumin and Transferrin.
AB  - A new type of thermosensitive dual-template epitope molecular imprinting polymer
      was prepared and coated on magnetic carbon nanotubes (MCNTs@D-EMIP) for
      simultaneous recognition of human serum albumin (HSA) and transferrin (Trf) via
      the strategies of dual-template epitope imprinting, metal chelation imprinting,
      and distillation-precipitation polymerization (DPP). C-terminal peptides of HSA
      and C-terminal peptides of Trf were selected as templates, zinc acrylate and N
      isopropylacrylamide were used as functional monomers, and MCNTs@D-EMIP was
      prepared by the method of DPP. The two types of template epitopes were
      immobilized by metal chelation and six-membered ring formed with zinc acylate.
      MCNTs@D-EMIP was prepared in only 30 min, which was much shorter than other
      polymerization methods. The resultant MCNTs@D-EMIP showed excellent specific
      recognition ability toward HSA and Trf. The adsorption amounts of MCNTs@D-EMIP
      for HSA and Trf were 103.67 and 68.48 mg g-1 and the imprinting factors were 2.57
      and 2.17, respectively. In addition, MCNTs@D-EMIP displayed a thermosensitive
      property to realize temperature-controlled recognition and release of target
      proteins. Furthermore, the results of high-performance liquid chromatography
      analysis proved that MCNTs@D-EMIP could be applied to specifically recognize two
      types of targets simultaneously in the biosample. The proposed strategy provided
      a preparation method for the thermosensitive dual-template epitope imprinting
      polymer via dual-template imprinting, metal chelation imprinting, and DPP.

PMID- 29461038
TI  - Portable Photoelectrochemical Device Integrated with Self-Powered Electrochromic
      Tablet for Visual Analysis.
AB  - A portable photoelectrochemical (PEC) device is developed by intergating a self
      powered electrochromic tablet for visual analysis. The tablet consists of an
      electron-injector (EI) part for photo-to-electric conversion and an
      electrochromic (EC) part for visualized readout, which are coated with dye
      sensitized titanium dioxide film and Ni-doped tungsten trioxide (WO3) film,
      respectively. Under the illumination of a white LED light, the photoexcited
      electrons generated from EI part convey to EC part through the conductive inner
      side of indium tin oxide slide and would cause color change of the Ni-doped WO3
      film in the presence of protons. Furthermore, the Ni-doped WO3 film exhibits
      excellent transmittance modulation of more than 80%, providing an enhanced signal
      for visual analysis. Using pyrophosphate ion (PPi) as a model analyte, we have
      successfully constructed a visualized PEC sensing platform based on the formation
      of blue-colored hydrogen tungsten bronzes via the hydrolysis reaction of PPi.
      Being equipped with a small light source and a dark box, the PEC tablet as a
      portable device can perform colorimetric measurement with good reversibility and
      stability. This smart PEC device provides important reference for future studies
      on the visual application in practice.

PMID- 29461039
TI  - Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD).
AB  - Lysergic acid diethylamide (LSD) is one of the most potent psychoactive agents
      known, producing dramatic alterations of consciousness after submilligram (>=20
      MUg) oral doses. Following the accidental discovery of its potent psychoactive
      effects in 1943, it was supplied by Sandoz Laboratories as an experimental drug
      that might be useful as an adjunct for psychotherapy, or to give psychiatrists
      insight into the mental processes in their patients. The finding of serotonin in
      the mammalian brain in 1953, and its structural resemblance to LSD, quickly led
      to ideas that serotonin in the brain might be involved in mental disorders,
      initiating rapid research interest in the neurochemistry of serotonin. LSD proved
      to be physiologically very safe and nonaddictive, with a very low incidence of
      adverse events when used in controlled experiments. Widely hailed by psychiatry
      as a breakthrough in the 1950s and early 1960s, clinical research with LSD ended
      by about 1970, when it was formally placed into Schedule 1 of the Controlled
      Substances Act of 1970 following its growing popularity as a recreational drug.
      Within the past 5 years, clinical research with LSD has begun in Europe, but
      there has been none in the United States. LSD is proving to be a powerful tool to
      help understand brain dynamics when combined with modern brain imaging methods.
      It remains to be seen whether therapeutic value for LSD can be confirmed in
      controlled clinical trials, but promising results have been obtained in small
      pilot trials of depression, anxiety, and addictions using psilocybin, a related
      psychedelic molecule.

PMID- 29461040
TI  - Encapsulating Chemically Doped Graphene via Atomic Layer Deposition.
AB  - Controlling graphene's doping will be critically important for its incorporation
      into future electronic and optoelectronic devices. Noncovalent functionalization
      through adsorption of organic molecules on graphene's surface has proved to be a
      promising route for achieving p- or n-type doping. However, due to the poor
      adhesion of the molecules, these tend to desorb over time under standard
      environmental conditions or in the presence of certain solvents. The resulting
      reversal in the achieved chemical doping is a major obstacle to using organic
      molecules as noncovalent graphene dopants. In this work, we present a simple
      method for achieving long-term p- and n-doping of graphene devices through vapor
      phase evaporation of organic molecules, followed by encapsulation under an inert
      Al2O3 film. This film, grown via an optimized atomic layer deposition process,
      ensures long-term doping stability, as confirmed by electrical transport and
      Raman spectroscopy measurements. The doping is maintained even after storing the
      devices for six weeks in ambient conditions and immersing them in a dopant
      removing solvent, demonstrating that the film is as an effective barrier against
      environmental degradation of the doped devices.

PMID- 29461041
TI  - Development of Graphene Oxide Composite Aerogel with Proanthocyanidins with
      Hemostatic Properties As a Delivery System.
AB  - The graphene aerogels' potential for use as both a hemostatic agent and dermal
      delivery system has scarcely been investigated. In this study, we used a sol-gel
      process for generating dry and stable composite aerogels based on graphene oxide
      (GO) and poly(vinyl alcohol) (PVA). Furthermore, we incorporated natural extract
      of Pais grape seed (SD) and skin (SK), rich in proanthocyanidins (PAs or
      condensed tannins). The effect of the incorporation of the grape extracts was
      investigated in relation to the aerogels' structure, coagulation performance and
      the release of the extracts. The results demonstrated that they have a porous
      structure and low density, capable of absorbing water and blood. The
      incorporation of 12% (w/w) of PA extracts into the aerogel increased the negative
      zeta potential of the material by 33% (-18.3 +/- 1.3 mV), and the coagulation
      time was reduced by 37% and 28% during the first 30 and 60 s of contact between
      the aerogel and whole blood, respectively. The release of extracts from the GO
      PVA-SD and GO-PVA-SK aerogels was prolonged to 3 h with 20%, probably due to the
      existence of strong binding between PAs andGO-PVA, both characterized by the
      presence of aromatic and hydroxyl groups that can form noncovalent bonds but are
      strong and stable enough to avoid a greater release into the medium. This study
      provides a new GO-based aerogel, which has a great potential use in the field of
      dermal delivery, wound healing and/or the treatment of trauma bleeding.

PMID- 29461042
TI  - Rational Design of Magnetic Micronanoelectrodes for Recognition and
      Ultrasensitive Quantification of Cysteine Enantiomers.
AB  - Driven by the urgent need for recognition and quantification of trace amino acids
      enantiomers in various biologic samples, we demonstrate for the first time an
      ultrasensitive electrochemical chiral biosensor for cysteine (Cys) based on
      magnetic nanoparticles (Fe3O4@PDA/Cu xO) as electrode units. d-Cys-Cu2+-d-Cys
      formed in the presence of cysteine exhibits strong stability and a shielding
      effect on the redox current of indicator Cu2+, which can be used to quantify and
      recognize d-Cys by square wave voltammetry. Simultaneous detection of d-Cys and
      homocysteine (Hcy) is achieved in the presence of other amino acids,
      demonstrating an excellent selectivity of the sensor. Moreover, aided by the
      enrichment treatment effect of magnetic micronanoelectrodes, an ultrahigh
      sensitivity up to 102 MUA MUM-1 cm-2 was achieved, the detection limit is reduced
      to picomolar level (83 pM) for d-Cys and can be used for the recognition of
      cysteine enantiomers. The proposed method has been verified by real sample
      analysis with satisfactory results. The results highlight the feasibility of our
      proposed strategy for magnetic micronanoelectrode sensor, electrochemical
      recognition, and quantification of d-Cys, which can be more broadly applicable
      than that with traditional electrode structures and further advance the field of
      electrochemical sensors.

PMID- 29461044
TI  - Antibiotic Susceptibility Determination within One Cell Cycle at Single-Bacterium
      Level by Stimulated Raman Metabolic Imaging.
AB  - The widespread use of antibiotics has significantly increased the number of
      resistant bacteria, which has also increased the urgency of rapid bacterial
      detection and profiling their antibiotic response. Current clinical methods for
      antibiotic susceptibility testing (AST) rely on culture and require at least 16
      to 24 h to conduct. Therefore, there is an urgent need for a rapid method that
      can test the susceptibility of bacteria in a culture-free manner. Here we
      demonstrate a rapid AST method by monitoring the glucose metabolic activity of
      live bacteria at the single-cell level with hyperspectral stimulated Raman
      scattering (SRS) imaging. Using vancomycin-susceptible and -resistant enterococci
      E. faecalis as models, we demonstrate that the metabolic uptake of deuterated
      glucose in a single living bacterium can be quantitatively monitored via
      hyperspectral SRS imaging. Remarkably, the metabolic activity of susceptible
      bacteria responds differently to antibiotics from the resistant strain within
      only 0.5 h from the addition of antibiotics. Therefore, bacterial susceptibility
      and the minimum inhibitory concentration (MIC) of antibiotics can be determined
      within one cell cycle. Our metabolic imaging method is applicable to other
      bacteria species including E. coli, K. Pneumoniae, and S. aureus as well as
      different antibiotics, regardless of their mechanisms of inhibiting or killing
      bacteria.

PMID- 29461043
TI  - Li4SiO4-Based Artificial Passivation Thin Film for Improving Interfacial
      Stability of Li Metal Anodes.
AB  - An amorphous SiO2 (a-SiO2) thin film was developed as an artificial passivation
      layer to stabilize Li metal anodes during electrochemical reactions. The thin
      film was prepared using an electron cyclotron resonance-chemical vapor deposition
      apparatus. The obtained passivation layer has a hierarchical structure, which is
      composed of lithium silicide, lithiated silicon oxide, and a-SiO2. The thickness
      of the a-SiO2 passivation layer could be varied by changing the processing time,
      whereas that of the lithium silicide and lithiated silicon oxide layers was
      almost constant. During cycling, the surface of the a-SiO2 passivation layer is
      converted into lithium silicate (Li4SiO4), and the portion of Li4SiO4 depends on
      the thickness of a-SiO2. A minimum overpotential of 21.7 mV was observed at the
      Li metal electrode at a current density of 3 mA cm-2 with flat voltage profiles,
      when an a-SiO2 passivation layer of 92.5 nm was used. The Li metal with this
      optimized thin passivation layer also showed the lowest charge-transfer
      resistance (3.948 Omega cm) and the highest Li ion diffusivity (7.06 * 10-14 cm2
      s-1) after cycling in a Li-S battery. The existence of the Li4SiO4 artificial
      passivation layer prevents the corrosion of Li metal by suppressing Li dendritic
      growth and improving the ionic conductivity, which contribute to the low charge
      transfer resistance and high Li ion diffusivity of the electrode.

PMID- 29461045
TI  - Electrochemical Sensing of Bisphenol A on Facet-Tailored TiO2 Single Crystals
      Engineered by Inorganic-Framework Molecular Imprinting Sites.
AB  - Noble metals, nanostructured carbon, and their hybrids are widely used for
      electrochemical detection of persistent organic pollutants. However, despite of
      the rapid detection process and high accuracy, these materials generally suffer
      from high costs, metallic impurity, heterogeneity, irreversible adsorption and
      poor sensitivity. Herein, the high-energy {001}-exposed TiO2 single crystals with
      specific inorganic-framework molecular recognition ability was prepared as the
      electrode material to detect bisphenol A (BPA), a typical and widely present
      organic pollutant in the environment. The oxidation peak current was linearly
      correlated to the BPA concentration from 10.0 nM to 20.0 MUM ( R2 = 0.9987), with
      a low detection limit of 3.0 nM (S/N = 3). Furthermore, it exhibited excellent
      discriminating ability, high anti-interference capacity, and good long-term
      stability. Its good performance for BPA detection in real environmental samples,
      including tap water, lake and river waters, domestic wastewater, and municipal
      sludge, was also demonstrated. This work extends the applications of TiO2
      semiconductor and suggests that this material could be used as a highly active,
      stable, low-cost, and environmentally benign electrode material for
      electrochemical sensing.

PMID- 29461046
TI  - Three-Dimensional-Bioprinted Dopamine-Based Matrix for Promoting Neural
      Regeneration.
AB  - Central nerve repair and regeneration remain challenging problems worldwide,
      largely because of the extremely weak inherent regenerative capacity and
      accompanying fibrosis of native nerves. Inadequate solutions to the unmet needs
      for clinical therapeutics encourage the development of novel strategies to
      promote nerve regeneration. Recently, 3D bioprinting techniques, as one of a set
      of valuable tissue engineering technologies, have shown great promise toward
      fabricating complex and customizable artificial tissue scaffolds. Gelatin
      methacrylate (GelMA) possesses excellent biocompatible and biodegradable
      properties because it contains many arginine-glycine-aspartic acids (RGD) and
      matrix metalloproteinase sequences. Dopamine (DA), as an essential
      neurotransmitter, has proven effective in regulating neuronal development and
      enhancing neurite outgrowth. In this study, GelMA-DA neural scaffolds with
      hierarchical structures were 3D-fabricated using our custom-designed
      stereolithography-based printer. DA was functionalized on GelMA to synthesize a
      biocompatible printable ink (GelMA-DA) for improving neural differentiation.
      Additionally, neural stem cells (NSCs) were employed as the primary cell source
      for these scaffolds because of their ability to terminally differentiate into a
      variety of cell types including neurons, astrocytes, and oligodendrocytes. The
      resultant GelMA-DA scaffolds exhibited a highly porous and interconnected 3D
      environment, which is favorable for supporting NSC growth. Confocal microscopy
      analysis of neural differentiation demonstrated that a distinct neural network
      was formed on the GelMA-DA scaffolds. In particular, the most significant
      improvements were the enhanced neuron gene expression of TUJ1 and MAP2. Overall,
      our results demonstrated that 3D-printed customizable GelMA-DA scaffolds have a
      positive role in promoting neural differentiation, which is promising for
      advancing nerve repair and regeneration in the future.

PMID- 29461047
TI  - Lithium and Sodium Ion Distributions in A2- x[W6I14] Structures.
AB  - Ag2[W6I14] and A2- x[W6I14] compounds with A = Na, Li were prepared from binary
      tungsten iodides (W3I12) and corresponding metal iodides. Their crystal
      structures are analyzed on the basis of X-ray diffraction data. 7Li and 23Na
      solid-state NMR measurements reveal that Li+ and Na+ ions are distributed over
      two sites in the respective structures. These results shed some new light on A
      x[M6I14] with A = alkali and M = Mo, W compounds being reported with x = 1 and 2,
      which exhibit photophysical properties. The lithium compound is an exception in
      the series of A2- x[W6I14] compounds, because it is the only compound which is
      soluble in water.

PMID- 29461048
TI  - Selective Recognition of Hg2+ ion in Water by a Functionalized Metal-Organic
      Framework (MOF) Based Chemodosimeter.
AB  - A metal-organic framework (MOF)-based highly selective and sensitive probe (UiO
      66@Butyne) for the detection of Hg(II) ion has been developed. To the best our
      knowledge, this is the foremost example of a chemodosimeter-based approach to
      sense Hg(II) ion using a MOF-based probe. The chemical stability of UiO-66@Butyne
      renders the sensitive detection of Hg2+ ion in an aqueous phase. UiO-66@Butyne
      has been found to be selective for Hg(II) ions even in the presence of other
      metal ions.

PMID- 29461049
TI  - Emerging Biodegradation of the Previously Persistent Artificial Sweetener
      Acesulfame in Biological Wastewater Treatment.
AB  - The persistence of acesulfame (ACE) in wastewater treatment (and subsequently the
      aquatic environment) has led to its use as a marker substance for wastewater
      input into surface water and groundwater. However, ACE degradation of >85% during
      summer and autumn was observed in nine German wastewater treatment plants
      (WWTPs). Annual removal performance was more stable in larger plants, enhanced by
      low biological oxygen demand and impeded by water temperatures below 10  degrees
      C. Literature data suggest that the potential to degrade ACE emerged in WWTPs
      around the year 2010. This development is ongoing, as illustrated by ACE content
      in the German rivers Elbe and Mulde: Between 2013 and 2016 the ACE mass load
      decreased by 70-80%. In enrichment cultures with ACE as sole carbon source the
      carbonaceous fraction of ACE was removed completely, indicating catabolic
      biotransformation and the inorganic compound sulfamic acid formed in quantitative
      amounts. Sequencing of bacterial 16S rRNA genes suggests that several species are
      involved in ACE degradation, with proteobacterial species affiliated to
      Phyllobacteriaceae, Methylophilaceae, Bradyrhizobiaceae, and Pseudomonas becoming
      specifically enriched. ACE appears to be the first micropollutant for which the
      evolution of a catabolic pathway in WWTPs has been witnessed. It can yet only be
      speculated whether the emergence of ACE removal in WWTPs in different regions of
      the world is due to independent evolution or to global spreading of genes or
      adapted microorganisms.

PMID- 29461050
TI  - Modular Access to Azepines by Directed Carbonylative C-C Bond Activation of
      Aminocyclopropanes.
AB  - A modular Rh-catalyzed entry to azepines is outlined. Under a CO atmosphere,
      protecting group directed C-C bond activation of aminocyclopropanes provides
      rhodacyclopentanones. These intermediates are effective for intramolecular C-H
      metalation of either an N-aryl or N-vinyl unit en route to azepine ring systems.
      Thus, byproduct-free heterocyclizations are enabled by sequential C-C activation
      and C-H functionalization steps.

PMID- 29461051
TI  - Mechanistic Investigations of Photoinduced Oxygenation of Ru(II) Bis-bipyridyl
      Flavonolate Complexes.
AB  - We previously reported that a Ru-bound flavonolate model of flavonol
      dioxygenases, [RuII(bpy)2(3-hydroxyfla)][PF6], photochemically reacts with
      dioxygen in two different manners. Broad-band excitation generates mixtures of
      products characteristic of 1,3-addition of dioxygen across the central pyrone
      ring, as is observed in enzymatic reactions. However, low temperature excitation
      at wavelengths longer than 400 nm generates a unique Ru-bound 2
      benzoatophenylglyoxylate product resulting from a 1,2-dioxetane intermediate.
      Herein, we investigate this reactivity in a series of Ru(II)bis-bipyridyl
      flavonolate complexes [RuII(bpy)2(3-hydroxyflaR)][PF6] (bpy = 2,2'-bipyridine;
      fla = flavonolate; R = p-OMe (1), p-Me (2), p-H (3), p-Cl (4)), and [RuII(bpy)2(5
      hydroxyfla)][PF6] (5). The complexes' structures, photophysical and
      electrochemical properties, and photochemical reactivity with oxygen were
      investigated in detail. Two different reaction product mixtures, from 1,2- and
      1,3-additions of dioxygen, are observed by illumination into distinct
      excitation/emission manifolds. By analogy to previous reports of excited state
      intramolecular proton transfer, the two manifolds are attributed to tautomeric
      diradicals that predict the observed reactivity patterns.

PMID- 29461052
TI  - Insights into B-Site Ordering in Double Perovskite-Type Ba3Ca1+ xNb2- xO9-delta
      (0 <= x <= 0.45): Combined Synchrotron and Neutron Diffraction and Electrical
      Transport Analyses.
AB  - Perovskite-type metal oxides are being used in a wide range of technologies,
      including fuel cells, batteries, electrolyzers, dielectric capacitors, and
      sensors. One of their remarkable structural properties is cationic ordering in A
      or B sites, which affects electrical transport properties under different gaseous
      atmospheres, and chemical stability under CO2 and humid conditions. For example,
      a simple-perovskite-type Y-doped BaCeO3 forms BaCO3 and ((Ce,Y)O2-delta) under
      CO2 at elevated temperature, while B-site-ordered double-perovskite-type
      Ba3Ca1.18Nb1.82O9-delta remains chemically stable under the same conditions.
      Early structural studies on Ba3Ca1+ xNb2- xO9-delta (BCN) showed that the B-site
      ordering (1:1) is sensitive to the Ca content. However, ambiguity rises, as 1:2 B
      site ordering was not observed in the parent and doped analogues when x was
      varied, which motivated us to revisit the complex oxides BCN ( x = 0-0.45) to
      determine the atomic structure by a mean of combined synchrotron X-ray and
      neutron diffraction methods. Surprisingly, the B-site ordering increases with
      increasing Ca/Nb mixing in the B-sites in BCN. In addition, the electrical
      conductivity of BCN was found to be the highest at x = ~0.18, and it decreased as
      the Ca/Nb ratio further increased in BCN. Such a result was very similar to that
      for the Y-doped BaZrO3, where the mobility of proton carriers was found to
      decrease as the dopant (Y) increased. A higher Ca/Nb ratio also promotes the
      growth of grain size, as Ca ions could serve as a sintering aid, improving the
      structural integrity.

PMID- 29461053
TI  - Research Progress of Polycyclic Polyprenylated Acylphloroglucinols.
AB  - Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of hybrid
      natural products sharing the mevalonate/methylerythritol phosphate and polyketide
      biosynthetic pathways and showing considerable structure and bioactivity
      diversity. This review discusses the progress of research into the chemistry and
      biological activity of 421 natural PPAPs in the past 11 years as well as in-depth
      studies of biological activities and total synthesis of some PPAPs isolated
      before 2006. We created an online database of all PPAPs known to date at
      http://www.chem.uky.edu/research/grossman/PPAPs . Two subclasses of
      biosynthetically related metabolites, spirocyclic PPAPs with
      octahydrospiro[cyclohexan-1,5'-indene]-2,4,6-trione core and complicated PPAPs
      produced by intramolecular [4 + 2] cycloadditions of MPAPs, are brought into the
      PPAP family. Some PPAPs' relative or absolute configurations are reassigned or
      critically discussed, and the confusing trivial names in PPAPs investigations are
      clarified. Pharmacologic studies have revealed a new molecular mechanism whereby
      hyperforin and its derivatives regulate neurotransmitter levels by activating
      TRPC6 as well as the antitumor mechanism of garcinol and its analogues. The
      antineoplastic potential of some type B PPAPs such as oblongifolin C and
      guttiferone K has increased significantly. As a result of the recent appearances
      of innovative synthetic methods and strategies, the total syntheses of 22 natural
      PPAPs including hyperforin, garcinol, and plukenetione A have been accomplished.

PMID- 29461054
TI  - Tripodal N,P Mixed-Donor Ligands and Their Cobalt Complexes: Efficient Catalysts
      for Acceptorless Dehydrogenation of Secondary Alcohols.
AB  - A new tetradentate tripodal ligand, iPrPPPNHPyMe, and the cobalt complexes were
      synthesized and characterized. The well-defined cobalt complexes efficiently
      catalyzed acceptorless dehydrogenation of secondary alcohols into ketones.

PMID- 29461055
TI  - Bidirectional Degradation of DNA Cleavage Products Catalyzed by CRISPR/Cas9.
AB  - Since the initial characterization of Streptococcus pyogenes CRISPR/Cas9 as a
      powerful gene-editing tool, it has been widely accepted that Cas9 generates blunt
      ended DNA products by concerted cleavage of the target (tDNA) and non-target
      (ntDNA) strands three nucleotides away from the protospacer adjacent motif (PAM)
      by HNH and RuvC nuclease active sites, respectively. Following initial DNA
      cleavage, RuvC catalyzes 3'->5' degradation of the ntDNA resulting in DNA
      products of various lengths. Here, we found that Cas9 selects multiple sites for
      initial ntDNA cleavage and preferentially generates staggered-ended DNA products
      containing single-nucleotide 5'-overhangs. We also quantitatively evaluated 3'
      >5' post-cleavage trimming (PCT) activity of RuvC to find that ntDNA degradation
      continues up to the -10 position on the PAM distal DNA product and is kinetically
      significant when compared to extremely slow DNA product release. We also
      discovered a previously unidentified 5'->3' PCT activity of RuvC which can
      shorten the PAM proximal ntDNA product by precisely one nucleotide with a
      comparable rate as the 3'->5' PCT activity. Taken together, our results
      demonstrate that RuvC-catalyzed PCT ultimately generates DNA fragments with
      heterogeneous ends following initial DNA cleavage including a PAM proximal
      fragment with a blunt end and a PAM distal fragment with a staggered-end, 3'
      recessed on the ntDNA strand. These kinetic and biochemical findings underline
      the importance of temporal control of Cas9 during gene-editing experiments and
      help explain the patterns of nucleotide insertions at sites of Cas9-catalyzed
      gene modification in vivo.

PMID- 29461056
TI  - Total Synthesis of Adunctin B.
AB  - Total synthesis of (+/-)-adunctin B, a natural product isolated from Piper
      aduncum (Piperaceae), has been achieved using two different strategies, in seven
      and three steps. The efficient approach features highly atom economical and
      diastereoselective Friedel-Crafts acylation, alkylation reaction and palladium
      catalyzed Wacker type oxidative cyclization.

PMID- 29461057
TI  - Elaboration of Cellulose Nanocrystal/Ge-Imogolite Nanotube Multilayered Thin
      Films.
AB  - Multilayered thin films combining two oppositely charged nanoparticles (NPs),
      i.e., cellulose nanocrystals (CNCs) and Ge-imogolites, have been successfully
      obtained by the layer-by-layer method. CNC/Ge-imogolite (NP/NP) film growth
      patterns were studied by comparing growth mode of all of the nanoparticles thin
      films to that of films composed of CNC or Ge-imogolites combined with
      polyelectrolytes (PEs), i.e., cationic poly(allylamine hydrochloride) and anionic
      poly-4-styrene sulfonate (NP/PE films). NP/NP and NP/PE films growth patterns
      were found to be different. To get a deeper understanding of the growth mode of
      NP/NP, impact of different parameters, such as imogolites aspect ratio,
      adsorption time, ionic strength, and repeated immersion/drying, was evaluated and
      influence of the drying step is emphasized. The aspect ratio of imogolites was
      identified as an important feature for the film's architecture. The short Ge
      imogolites form denser films because the surface packing was more efficient.

PMID- 29461058
TI  - Intramolecular Photocycloaddition of 2(5 H)-Furanones to Temporarily Tethered
      Terminal Alkenes as a Stereoselective Source of Enantiomerically Pure
      Polyfunctionalyzed Cyclobutanes.
AB  - Allyloxymethyloxymethyl and 4-pentenoyloxymethyl substituents have been used as
      tethering groups to study the intramolecular [2 + 2] photocycloaddition of chiral
      5-substituted 2(5 H)-furanones. The photoreactions proceed in good yield and
      provide the expected regio- and diastereoselective tricyclic compounds with
      complementary regioselectivity, which depends on whether the vinyl chain is
      attached to the furanone by an acetal or an ester linkage. Computational
      simulations agree with experimental observations and indicate that the origin of
      the different observed regioselectivity in the intramolecular photochemical
      reaction of lactones 5 and 6 arises from the relative stability of the initial
      conformers. The synthetic potential of the enantiomerically pure photoadducts is
      illustrated by preparing an all- cis 1,2,3-trisubstituted cyclobutane bearing
      fully orthogonally protected hydroxyl groups.

PMID- 29461059
TI  - Role of Dimers in the cAMP-Dependent Activation of Hyperpolarization-Activated
      Cyclic-Nucleotide-Modulated (HCN) Ion Channels.
AB  - Hyperpolarization-activated cyclic-nucleotide-modulated (HCN) ion channels
      control rhythmicity in neurons and cardiomyocytes. Cyclic AMP (cAMP) modulates
      HCN activity through the cAMP-induced formation of a tetrameric gating ring
      spanning the intracellular region (IR) of HCN. Although evidence from confocal
      patch-clamp fluorometry indicates that the cAMP-dependent gating of HCN occurs
      through a dimer of dimers, the structural and dynamical basis of cAMP allostery
      in HCN dimers has so far remained elusive. Thus, here we examine how dimers
      influence IR structural dynamics, and the role that such structural dynamics play
      in HCN allostery. To this end, we performed molecular dynamics (MD) simulations
      of HCN4 IR dimers in their fully apo, fully holo, and partially cAMP-bound
      states, resulting in a total simulated time of 1.2 MUs. Comparative analyses of
      these MD trajectories, as well as previous monomer and tetramer simulations
      utilized as benchmarks for comparison, reveal that dimers markedly sensitize the
      HCN IR to cAMP-modulated allostery. Our results indicate that dimerization fine
      tunes the IR dynamics to enhance, relative to both monomers and tetramers, the
      allosteric intra- and interprotomer coupling between the cAMP-binding domain and
      tetramerization domain components of the IR. The resulting allosteric model
      provides a viable rationalization of electrophysiological data on the role of IR
      dimers in HCN activation.

PMID- 29461060
TI  - Anomalous Solubility of an Inert Solid in a Binary Liquid Mixture with a Critical
      Point of Solution.
AB  - We consider the dissolution of a chemically inert solid in a binary liquid
      mixture with a critical point of solution. When the mixture, acting as the
      solvent, has come to equilibrium with the solid, the state of the system is
      completely described by the temperature, pressure, and a concentration variable
      formed by dividing the molar amount of one solvent component by that of the
      other. Under conditions of fixed pressure, the principle of critical point
      isomorphism predicts that the slope of a van't Hoff plot of the solubility of the
      solid should diverge toward infinity as the temperature enters the critical
      region. The sign of the divergence is negative when the dissolution is
      endothermic, whereas it is positive when the dissolution is exothermic. In
      experiments where excess solid phenolphthalein dissolves in a binary mixture of
      nitrobenzene + dodecane, we have observed exothermic dissolution concurrently
      with a positive divergence of the van't Hoff slope. The data are insufficiently
      precise to compute an accurate numerical value for the exponent of the
      temperature power law expected to govern this divergence; nevertheless, on the
      basis of Widom scaling theory, we argue that the exponent should be equal to
      0.326, which is identical to the value of the exponent that governs the
      temperature dependence of the shape of the liquid-liquid coexistence curve. Being
      entirely physical in nature, the anomalous solubility effect should be observable
      in the case of any chemically inert solid dissolving in any one of the more than
      1000 liquid pairs known to have a critical point of solution.

PMID- 29461061
TI  - Electrical Stressing Induced Monolayer Vacancy Island Growth on TiSe2.
AB  - To ensure practical applications of atomically thin transition metal
      dichalcogenides, it is essential to characterize their structural stability under
      external stimuli such as electric fields and currents. Using vacancy monolayer
      islands on TiSe2 surfaces as a model system, we have observed nonlinear area
      evolution and growth from triangular to hexagonal driven by scanning tunneling
      microscopy (STM) subjected electrical stressing. The observed growth dynamics
      represent a 2D departure from the linear area growth law expected for bulk
      vacancy clustering. Our simulations of monolayer island evolution using phase
      field modeling and first-principles calculations are in good agreement with our
      experimental observations, and point toward preferential edge atom dissociation
      under STM scanning driving the observed nonlinear area growth. We further
      quantified a parabolic growth rate dependence with respect to the tunneling
      current magnitude. The results could be potentially important for device
      reliability in systems containing ultrathin transition metal dichalcogenides and
      related 2D materials subject to electrical stressing.

PMID- 29461062
TI  - Understanding the MXene Pseudocapacitance.
AB  - MXenes have attracted great attention as next-generation capacitive energy
      storage materials, but the mechanisms underlying their pseudocapacitive behavior
      are not well understood. Here we provide a theoretical description of the surface
      redox process of Ti3C2T x (T = O, OH), a prototypical MXene, in 1 M H2SO4
      electrolyte, based on joint density functional theory with an implicit solvation
      model and the analysis of Gibbs free energy under a constant-electrode potential.
      From the dependence of the O/OH ratio (or the surface H coverage) and the surface
      charge on the applied potential, we obtain a clear picture of the capacitive
      energy-storage mechanism of Ti3C2T x that shows good agreement with previous
      experimental findings in terms of the integral capacitance and Ti valence change.
      We find a voltage-dependent redox/double-layer co-charging behavior: the
      capacitive mechanism is dominated by the redox process, but the electric double
      layer charge works against the redox process. This new insight may be useful in
      improving the capacitance of MXenes.

PMID- 29461063
TI  - Nickel-Catalyzed Reductive Bis-Allylation of Alkynes.
AB  - A reductive nickel-catalyzed bis-allylation of alkynes with allyl acetates has
      been developed, leading to 1,4,7-triene skeletons. This reductive bis-allylation
      proceeds under mild conditions and exhibits good functional group tolerance in
      both the allyl acetates and the alkynes.

PMID- 29461065
TI  - Palladium-Catalyzed Enantioselective Synthesis of Cyclic Sulfamidates and
      Application to a Synthesis of Verubecestat.
AB  - An enantioselective arylation reaction catalyzed by palladium complexed with
      substituted phosphinooxazoline (PHOX) ligands is described. Aza-quaternary
      stereocenters are readily accessible through the arylation reaction between
      cyclic iminosulfates and a wide variety of arylboronic acids, including electron
      poor and ortho-substituted arylboronic acids. This reaction was applied to the
      preparation of verubecestat, which is currently undergoing clinical evaluation
      for the treatment of Alzheimer's disease.

PMID- 29461064
TI  - Enantioselective Synthesis of alpha-(Hetero)aryl Piperidines through Asymmetric
      Hydrogenation of Pyridinium Salts and Its Mechanistic Insights.
AB  - Enantioselective synthesis of alpha-aryl and alpha-heteroaryl piperidines is
      reported. The key step is an iridium-catalyzed asymmetric hydrogenation of
      substituted N-benzylpyridinium salts. High levels of enantioselectivity up to
      99.3:0.7 er were obtained for a range of alpha-heteroaryl piperidines. DFT
      calculations support an outersphere dissociative mechanism for the pyridinium
      reduction. Notably, initial protonation of the final enamine intermediate
      determines the stereochemical outcome of the transformation rather than hydride
      reduction of the resultant iminium intermediate.

PMID- 29461066
TI  - Chemically Diverse Helix-Constrained Peptides Using Selenocysteine Crosslinking.
AB  - The use of selenocysteines and various cross-linkers to induce helicity in a
      bioactive peptide is described. The higher reactivity of selenocysteine, relative
      to cysteine, facilitates rapid cross-linking within unprotected linear peptides
      under mild aqueous conditions. Alkylating agents of variable topology and
      electrophilicity were used to link pairs of selenocysteines within a p53 peptide.
      Facile selenoether formation enables diverse tailoring of the helical peptide
      structure.

PMID- 29461068
TI  - Social learning and associative processes: A synthesis.
AB  - Social learning is often considered different from asocial learning in both its
      characteristics and mechanisms. I presented pigeons with a concurrent
      discrimination task in which they received artificial social information,
      consisting of simple shapes that distributed themselves between two options
      similarly to how conspecifics might. Subjects in some conditions combined
      personal information about the two options with this social-like information, but
      subjects in conditions in which personal information was very reliable ignored
      the social cues, much like cases in which animals only choose to copy choices of
      others under certain conditions. I present a modification of a popular
      associative model of individual learning that can replicate these results,
      despite not distinguishing between social and asocial cues. The model suggests
      that the adaptive use of social information does not require the assumption of
      specifically social learning strategies, but may be driven by the overshadowing
      of less reliable asocial cues by more reliable social cues. (PsycINFO Database
      Record

PMID- 29461067
TI  - Perceptual boundaries cause mnemonic trade-offs between local boundary processing
      and across-trial associative binding.
AB  - Episodic memories are not veridical records of our lives, but rather are better
      described as organized summaries of experience. Theories and empirical research
      suggest that shifts in perceptual, temporal, and semantic information lead to a
      chunking of our continuous experiences into segments, or "events." However, the
      consequences of these contextual shifts on memory formation and organization
      remains unclear. In a series of 3 behavioral studies, we introduced context
      shifts (or "event boundaries") between trains of stimuli and then examined the
      influence of the boundaries on several measures of associative memory. In
      Experiment 1, we found that perceptual event boundaries strengthened associative
      binding of item-context pairings present at event boundaries. In Experiment 2, we
      observed reduced temporal order memory for items encoded in distinct events
      relative to items encoded within the same event, and a trade-off between the
      speed of processing at boundaries, and temporal order memory for items that
      flanked those boundaries. Finally, in Experiment 3 we found that event
      organization imprinted structure on the order in which items were freely
      recalled. These results provide insight into how boundary- and event-related
      organizational processes during encoding shape subsequent representations of
      events in episodic memory. (PsycINFO Database Record

PMID- 29461069
TI  - Testing principal- versus medial-axis accounts of global spatial reorientation.
AB  - Determination of a direction of travel is a necessary component of successful
      navigation, and various species appear to use the geometric shape (global
      geometric cues) of an environment to determine direction. Yet, debate remains
      concerning which objective shape parameter is responsible for spatial
      reorientation via global geometric cues. For example, the principal axis of
      space, which runs through the centroid and approximate length of the space, and
      the medial axis of space, a trunk and branch system that fills the shape, have
      each been suggested as a basis to explain global spatial reorientation. As the
      principal- and medial-axis accounts appear to have substantial theoretical
      implications regarding the nature of shape perception, spatial memory, and the
      underlying psychological representations of space, it appears critical to
      empirically differentiate between these global geometric accounts. The present
      experiment explicitly placed predictions from the principal- and medial-axis
      based accounts of global spatial reorientation in conflict for theoretical
      diagnostic purposes. We used a standard reorientation paradigm in which human
      participants first reoriented in a rectangular environment; subsequent testing in
      a critical I-shaped enclosure allowed dissociation of the principal- or medial
      axis-based accounts. We show that reorientation in the I-shaped enclosure was
      consistent with the principal-axis account and inconsistent with the medial-axis
      account. We suggest that the use of the principal axis for spatial reorientation
      is a relatively simple and efficient way to establish directionality that would
      be advantageous over a more complex and less efficient medial-axis-based account.
      (PsycINFO Database Record

PMID- 29461070
TI  - A randomized trial of contingency management for smoking cessation in the
      homeless.
AB  - Smoking-cessation services are an unmet need among the homeless, who smoke at
      rates more than 4 times the national estimate. Successful interventions have high
      potential for improving tobacco-related health disparities among homeless
      smokers. Contingency management (CM) is a behavioral intervention with efficacy
      in a number of substance-use disorder populations, including smokers. However, no
      randomized studies have evaluated the effect of CM in homeless smokers. We
      examined smoking-related outcomes in homeless smokers (N = 70) randomized to
      standard-care (SC) smoking cessation involving transdermal nicotine-replacement
      therapy (NRT), standard counseling, and carbon monoxide (CO) monitoring or the
      same SC plus CM for negative CO sample submissions. Participants randomized to CM
      achieved significantly longer durations of consecutive abstinence and submitted a
      significantly higher proportion of CO-negative samples relative to standard-care
      participants. At 4 weeks postquit day, 22% were abstinent in the CM condition and
      9% were abstinent in the SC condition. At the 6-month follow-up, about 10% of
      smokers in both conditions were abstinent. This study demonstrates that CM is an
      efficacious option to increase initial quit rates in homeless smokers, but
      methods to extend effects are needed. (PsycINFO Database Record

PMID- 29461072
TI  - Nurturing the hope of youth in care: The contribution of mentoring.
AB  - Hope has long been viewed as important to individuals attempting to overcome
      obstacles. Overall hope is the combination of one's appraisal of capability and
      determination to achieve goals (Agency) and identifying viable routes to reach
      them (Pathway) (Snyder, 1994). The main goal of this study was to examine the
      incremental contribution of mentoring to hope among youth on the verge of leaving
      care above and beyond related personal characteristics and placement history. The
      sample included 148 adolescents in residential care in Israel who had adult
      mentors (ages 16-19). Results showed that lower levels of parental education and
      being in a welfare residential placement were associated with decreased levels of
      hope. Mentoring length and various mentoring functions ("role model," "parental
      figure," and "independence promoter") were found to have a significant
      contribution to the prediction of hope above and beyond associated individual and
      placement variables. Based upon these findings, residential care leaders should
      recruit and select mentors for longevity, and train mentors to serve as role
      models and parental figures who focus on independent living in order to influence
      hope among youth who are about to leave care. (PsycINFO Database Record

PMID- 29461071
TI  - Borderline personality disorder affective instability: What you know impacts how
      you feel.
AB  - The current study examined the role of conceptual knowledge and language in
      affective instability (AI) associated with borderline personality disorder (BPD).
      Forty-six females meeting criteria for BPD and 51 nonclinical female control
      participants without BPD completed a measure of general vocabulary and a semantic
      similarities task that provided estimates of the degree to which participants
      weighted information about valence and arousal in their understanding of emotion
      language. Feelings of valence and arousal were assessed using the Self-Assessment
      Manikin in response to 62 emotionally evocative images, which was used to derive
      estimates of AI. BPD status was associated with valence and arousal AI at a
      bivariate level, but not after controlling for language variables (general
      vocabulary and semantic valence and arousal foci). Participants with stronger as
      opposed to weaker vocabularies exhibited less AI, and participants who emphasized
      arousal more in their conceptual representations of emotions exhibited less AI
      than those who emphasized it to a lesser degree. With the inclusion of language
      variables in a regression equation with BPD status predicting AI, semantic
      arousal focus, but not general vocabulary, was a significant predictor of AI.
      Consistent with psychological constructionist models of emotion that specify an
      active role of language throughout the emotion generation process, these findings
      suggest that language capacity (general vocabulary and the degree to which
      arousal influences understanding of emotion words) is an important determinant of
      the AI associated with BPD. (PsycINFO Database Record

PMID- 29461073
TI  - Rethinking the acculturation gap-distress theory among asian americans: Testing
      bidirectional indirect relations.
AB  - The acculturation gap-distress theory postulates that parent-offspring
      acculturation mismatch precipitates greater intergenerational conflict in
      immigrant families, which in turn increases the risk for psychological problems
      among offspring. Whereas cross-sectional studies have shown support for these
      theory-informed relations, comparatively little is known about whether
      acculturation mismatch negatively affects psychological functioning, or whether
      offspring's psychological problems precipitate greater perceived acculturation
      mismatch via intergenerational cultural conflict. Furthermore, more research is
      needed to investigate how acculturation and family conflict affect Asian
      Americans transitioning into college and emerging adulthood. Across two
      measurement occasions, two cohorts of Asian American first-year college students
      (N = 555, Mage = 17.99, 56.0% women) completed survey questionnaires assessing
      their perception of parent-offspring acculturation discrepancies, acculturation
      related intergenerational conflict, and internalizing and externalizing symptoms.
      For both sets of psychological functioning, gender invariant structural equation
      models testing the bidirectional relations demonstrated adequate fit for the
      data. In the case of externalizing symptoms, acculturation mismatch marginally
      significantly predicted subsequent intergenerational conflict, but acculturation
      mismatch did not predict externalizing symptoms via intergenerational cultural
      conflict. By contrast, offspring's internalizing and externalizing symptoms
      respectively predicted greater self-reported intergenerational cultural conflict,
      which in turn predicted perceived parent-offspring acculturation mismatch over
      time. These indirect relations suggested that both internalizing and
      externalizing symptoms indirectly contributed to greater acculturation mismatch
      through the presence of intergenerational cultural conflict, but data did not
      support the acculturation gap-distress theory. Theoretical and clinical
      implications as they pertain to Asian American emerging adults are discussed.
      (PsycINFO Database Record

PMID- 29461074
TI  - Top-down contributions to attention shifting and disengagement: A template model
      of visual attention.
AB  - Two separate systems are involved in the control of spatial attention; one that
      is driven by a goal, and the other that is driven by stimuli. While the goal- and
      stimulus-driven systems follow different general principles, they also interplay
      with each other. However, the mechanism by which the goal-driven system
      influences the stimulus-driven system is still debated. The present study
      examined top-down contributions to two components of attention orienting,
      shifting and disengagement, with an experimental paradigm in which participants
      held a visual item in short-term memory (STM) and performed a prosaccade task
      with a manipulation of the gap between fixation offset and target onset. Four
      experiments showed that the STM content accelerated shifting and impaired
      disengagement, but the influence on disengagement depended on the utility of STM
      in guiding attention toward the target. Thus, the use of STM was strategic.
      Computational models of visual attention were fitted to the experimental data,
      which suggested that the top-down contributions to shifting was more prominent
      than those to disengagement. The results indicate that the current modeling
      framework was particularly useful when examining the contributions of theoretical
      constructs for the control of visual attention, but it also suggests limitations.
      (PsycINFO Database Record

PMID- 29461075
TI  - Editorial.
AB  - In this editorial, the incoming editor expresses his aspirations to continue to
      support Emotion's primary mission to publish high quality theory-driven,
      empirical research on emotion and to attract the very best research across all
      relevant areas of psychology and related fields. (PsycINFO Database Record

PMID- 29461076
TI  - The single lineup paradigm: A new way to manipulate target presence in eyewitness
      identification experiments.
AB  - The suspect in eyewitness lineups may be guilty or innocent. These possibilities
      are traditionally simulated in eyewitness identification studies using a dual
      lineup paradigm: All witnesses observe the same perpetrator and then receive one
      of two lineups. In this paradigm, the suspect's guilt is manipulated by including
      the perpetrator in one lineup and an innocent suspect in the other. The lineup is
      then filled with people matched to either the suspect (resulting in different
      fillers in perpetrator-present and perpetrator-absent lineups) or to the
      perpetrator (resulting in the same fillers in each lineup). An inescapable
      feature of the dual-lineup paradigm is that the perpetrator-present and
      perpetrator-absent lineups differ not only in the suspect's guilt, but also in
      their composition. Here, we describe a single-lineup paradigm: Subjects observe
      one of two perpetrators and then all subjects receive the same lineup containing
      one of the perpetrators. This alternative paradigm allows manipulation of the
      suspect's guilt without changing the lineup's composition. In three experiments,
      we applied the single-lineup paradigm to explore suspect-filler similarity and
      consistently found that increasing similarity reduced perpetrator identifications
      but did little to prevent innocent suspect misidentifications. Conversely, when
      fillers were matched to the perpetrator using a dual-lineup paradigm, increasing
      similarity reduced identification of perpetrators and innocent suspects. This
      finding suggests that the effect of filler similarity may depend on the person to
      whom the fillers are matched. We suggest that the single-lineup paradigm is a
      more ecologically valid and better controlled approach to creating suspect
      matched lineups in laboratory investigations of eyewitness memory than existing
      procedures. (PsycINFO Database Record

PMID- 29461077
TI  - Who deserves basic rights? People condone violations of procedural and physical
      rights in the treatment of terrorist suspects.
AB  - Public discourse regarding the treatment of terrorist suspects typically
      emphasizes utilitarian "greater-good" justifications related to ensuring public
      safety. By contrast, we hypothesized that laypeople's judgments of how suspected
      terrorists ought to be treated are more strongly informed by retributive concerns
      related to deservingness. Participants (N = 607, Mage = 34.25, recruited via
      Mechanical Turk) read about a terrorist suspect who was (vs. was not) presented
      as deserving of punishment and described as posing (vs. not posing) a continued
      threat to public safety. Participants rated the acceptability of procedural and
      physical rights violations occurring during the arrest and interrogation of the
      suspect and provided their perceptions of the suspect's dangerousness and
      deservingness of lawful treatment. We found that participants were more willing
      to condone rights violations when the suspect was (vs. was not) deserving of
      punishment. This willingness was not affected by the continued threat
      manipulation. Moreover, the effect of the punishment deservingness manipulation
      was mediated by perceptions that suspected terrorists are less deserving of
      having their rights upheld, but not by perceived dangerousness. Retributive
      concerns related to deservingness can thus lead people to condone the denial of
      suspected terrorists' basic rights, which may have consequences for the
      curtailment of all citizens' civil liberties. (PsycINFO Database Record

PMID- 29461078
TI  - Police managers' self-control and support for organizational justice.
AB  - Recent policing research has identified a positive relationship between line
      level officers' perceptions of organizational justice and their adherence to
      agency goals and job satisfaction. However, we have little understanding of the
      factors that are related to police managers' support for organizational justice
      when interacting with employees. We collected survey data from a sample of U.S.
      command-level officers (N = 211) who attended a training program in a southern
      state to address this gap in the literature. The anonymous survey was
      administered in-person to participating command-level police officers prior to
      their training program. Our multivariate regression analysis revealed that police
      managers who reported higher levels of self-control were more supportive of
      organizational justice (b = .26, p < .01). Additionally, police managers who
      reported higher quality relationships with their colleagues expressed greater
      support for organizational justice (b = .02, p = .02). Respondents' self
      legitimacy was not significantly associated with their support for organizational
      justice. This study contributes to the organizational justice literature by
      presenting the first analysis that links police commanders' self-control to
      support for organizational justice within their management practices. The
      findings help pinpoint the types of individuals who may be best equipped to be
      fair police managers. (PsycINFO Database Record

PMID- 29461079
TI  - Neural activity in the reward-related brain regions predicts implicit self
      esteem: A novel validity test of psychological measures using neuroimaging.
AB  - Self-esteem, arguably the most important attitudes an individual possesses, has
      been a premier research topic in psychology for more than a century. Following a
      surge of interest in implicit attitude measures in the 90s, researchers have
      tried to assess self-esteem implicitly to circumvent the influence of biases
      inherent in explicit measures. However, the validity of implicit self-esteem
      measures remains elusive. Critical tests are often inconclusive, as the validity
      of such measures is examined in the backdrop of imperfect behavioral measures. To
      overcome this serious limitation, we tested the neural validity of the most
      widely used implicit self-esteem measure, the implicit association test (IAT).
      Given the conceptualization of self-esteem as attitude toward the self, and
      neuroscience findings that the reward-related brain regions represent an
      individual's attitude or preference for an object when viewing its image,
      individual differences in implicit self-esteem should be associated with neural
      signals in the reward-related regions during passive-viewing of self-face (the
      most obvious representation of the self). Using multi-voxel pattern analysis
      (MVPA) on functional MRI (fMRI) data, we demonstrate that the neural signals in
      the reward-related regions were robustly associated with implicit (but not
      explicit) self-esteem, thus providing unique evidence for the neural validity of
      the self-esteem IAT. In addition, both implicit and explicit self-esteem were
      related, although differently, to neural signals in regions involved in self
      processing. Our finding highlights the utility of neuroscience methods in
      addressing fundamental psychological questions and providing unique insights into
      important psychological constructs. (PsycINFO Database Record

PMID- 29461080
TI  - Appraisal-driven facial actions as building blocks for emotion inference.
AB  - Although research on facial emotion recognition abounds, there has been little
      attention on the nature of the underlying mechanisms. In this article, using a
      "reverse engineering" approach, we suggest that emotion inference from facial
      expression mirrors the expression process. As a strong case can be made for an
      appraisal theory account of emotional expression, which holds that appraisal
      results directly determine the nature of facial muscle actions, we claim that
      observers first detect specific appraisals from different facial muscle actions
      and then use implicit inference rules to categorize and name specific emotions.
      We report three experiments in which, guided by theoretical predictions and past
      empirical evidence, we systematically manipulated specific facial action units
      individually and in different configurations via synthesized avatar expressions.
      Large, diverse groups of participants judged the resulting videos for the
      underlying appraisals and/or the ensuing emotions. The results confirm that
      participants can infer targeted appraisals and emotions from synthesized facial
      actions based on appraisal predictions. We also report evidence that the ability
      to correctly interpret the synthesized stimuli is highly correlated with emotion
      recognition ability as part of emotional competence. We conclude by highlighting
      the importance of adopting a theory-based experimental approach in future
      research, focusing on the dynamic unfolding of facial expressions of emotion.
      (PsycINFO Database Record

PMID- 29461081
TI  - The description of situations: Towards replicable domains of psychological
      situation characteristics.
AB  - Using the most comprehensive lexical approach with English adjectives to date,
      Parrigon et al. (2017) found 7 major dimensions of psychological situation
      characteristics (CAPTION: Complexity, Adversity, Positive Valence, Typicality,
      Importance, humOr, Negative Valence). Researchers using or studying situations
      may be interested in how well these dimensions empirically overlap with
      dimensions from other taxonomies, such as the DIAMONDS (Duty, Intellect,
      Adversity, Mating, pOsitivity, Negativity, Deception, Sociality). This comment
      highlights empirical and theoretical convergences between CAPTION and DIAMONDS
      scales, yielding evidence for 5 replicable dimensions. In general, average
      convergent correlations were substantial (.47-.69), much larger than discriminant
      ones (.18-.30), and as high as or higher than those typically found for Big Five
      scales. We highlight the opportunity to integrate different situation
      characteristics taxonomies and conclude with the plea for large-scale, cross
      cultural research that can further expand our knowledge on the structures of
      situation characteristics. (PsycINFO Database Record

PMID- 29461082
TI  - Why bottom-up taxonomies are unlikely to satisfy the quest for a definitive
      taxonomy of situations.
AB  - The recent advent of methods for large-scale data collection has provided an
      unprecedented opportunity for researchers who seek to develop a taxonomy of
      situations. Parrigon, Woo, Tay, and Wang's (2017) CAPTIONs model is the latest
      such effort. In this comment, I argue that although bottom-up approaches of this
      sort have clear value, they are unlikely to provide the sort of definitive,
      comprehensive, and theoretically integrative taxonomy that the field wants and
      needs. In large part, this is because bottom-up taxonomies represent what is
      common about situations and not what is theoretically important and influential
      about them. (PsycINFO Database Record

PMID- 29461083
TI  - Towards a comprehensive science of situations: On the importance of typicality
      and the lexical approach.
AB  - The two commentaries to the CAPTION derivation paper (Parrigon, Woo, Tay, & Wang,
      2017) provided insightful points regarding the consistency of emergent
      dimensional structures in the extant literature (Rauthmann & Sherman, 2018, p.
      482) and potential concerns regarding the use of the lexical approach to identify
      psychologically important situation dimensions (Reis, 2018, p. 489). In this
      rejoinder, we seek to further these important discussions by (a) emphasizing the
      importance of Typicality in understanding a broad range of psychological
      processes, (b) clarifying the utility of broad, dimensional-based situation
      taxonomies such as the CAPTION model for providing key theoretical and empirical
      linkages across discrete situations, as well as for capturing a broad range of
      psychologically meaningful dimensions of situations, and (c) reaffirming the need
      for cross-cultural/language and facet-level investigations of the CAPTION
      dimensions in future research. We hope that these discussions continue to advance
      the field toward a more comprehensive science of situations. (PsycINFO Database
      Record

PMID- 29461086
TI  - Instagram addiction and the Big Five of personality: The mediating role of self
      liking.
AB  - Background and aims Recent research has suggested that social networking site use
      can be addictive. Although extensive research has been carried out on potential
      addiction to social networking sites, such as Facebook, Twitter, YouTube, and
      Tinder, only one very small study has previously examined potential addiction to
      Instagram. Consequently, the objectives of this study were to examine the
      relationships between personality, self-liking, daily Internet use, and Instagram
      addiction, as well as exploring the mediating role of self-liking between
      personality and Instagram addiction using path analysis. Methods A total of 752
      university students completed a self-report survey, including the Instagram
      Addiction Scale (IAS), the Big Five Inventory (BFI), and the Self-Liking Scale.
      Results Results indicated that agreeableness, conscientiousness, and self-liking
      were negatively associated with Instagram addiction, whereas daily Internet use
      was positively associated with Instagram addiction. The results also showed that
      self-liking partially mediated the relationship of Instagram addiction with
      agreeableness and fully mediated the relationship between Instagram addiction
      with conscientiousness. Discussion and conclusions This study contributes to the
      small body of literature that has examined the relationship between personality
      and social networking site addiction and is one of only two studies to examine
      the addictive use of Instagram and the underlying factors related to it.

PMID- 29461088
TI  - Oral health and later coronary heart disease: Cohort study of one million people.
AB  - Aims Systematic reviews report an association between poorer oral health and an
      increased risk of coronary heart disease. This contentious relationship may not
      be causal but existing studies have been insufficiently well powered
      comprehensively to examine the role of confounding, particularly by cigarette
      smoking. Accordingly, we sought to examine the role of smoking in generating the
      relationship between oral health and coronary heart disease in life-long non
      smokers. Methods and results In the Korean Cancer Prevention Study, 975,685
      individuals (349,579 women) aged 30-95 years had an oral examination when tooth
      loss, a widely used indicator of oral health, was ascertained. Linkage to
      national mortality and hospital registers over 21 years of follow-up gave rise to
      64,784 coronary heart disease events (19,502 in women). In the whole cohort,
      after statistical adjustment for age, there was a moderate, positive association
      between tooth loss and coronary heart disease in both men (hazard ratio for seven
      or more missing teeth vs. none; 95% confidence interval 1.08; 1.02, 1.14; Ptrend
      across tooth loss groups <0.0001) and women (1.09; 1.01, 1.18; Ptrend 0.0016).
      Restricting analyses to a subgroup of 464,145 never smokers (25,765 coronary
      heart disease events), however, resulted in an elimination of this association in
      men (1.01; 0.85, 1.19); Ptrend 0.7506) but not women (1.08; 0.99, 1.18; Ptrend
      0.0086). Conclusion In men in the present study, the relationship between poor
      oral health and coronary heart disease risk appeared to be explained by
      confounding by cigarette smoking so raising questions about a causal link.

PMID- 29461089
TI  - Low volume, high intensity: Time-efficient exercise for the treatment of
      hypertension.

PMID- 29461087
TI  - Ufmylation Is Activated in Vascular Remodeling and Lipopolysaccharide-Induced
      Endothelial Cell Injury.
AB  - Vascular remodeling is a key process leading to arterial stenosis. Ufmylation, a
      novel ubiquitin-like modification, was observed to be associated with many
      biological processes. However, whether ufmylation is involved in the regulation
      of vascular remodeling remains unclear. Therefore, the present study focused on
      the role of ufmylation in vascular remodeling. Mouse femoral artery guidewire
      injury models were used for inducing vascular remodeling. We found that the
      expression of Ufm1 was upregulated in hyperplastic neointima. By treating
      vascular smooth muscle cells (VSMCs) with platelet-derived growth factor BB (PDGF
      BB) for 3, 6, 12, and 24 h, respectively, we observed that ufmylation was
      significantly activated in a time-dependent manner. Consistently, the expression
      levels of Ufc1, Ufl1, and Ufbp1, as key components of the ufmylation system, were
      all upregulated by PDGF-BB. In contrast, knockdown of Ufm1 expression attenuated
      PDGF-BB-induced VSMC proliferation. In addition, we observed that ufmylation was
      activated by lipopolysaccharide (LPS) in endothelial cells, whereas knockdown of
      Ufm1 was synergized with LPS-induced endothelial cell injury. These findings
      indicate that ufmylation may participate in regulation of the VSMC phenotypic
      switch and endothelial cell injury, which may help in the understanding of
      vascular remodeling.

PMID- 29461094
TI  - Utilizing neuronavigation for virtual electrode representation and safe resection
      following SEEG; a technical report.
AB  - PURPOSE: One of the most effective treatments for epilepsy is resection, but it
      remains underutilized. Efforts must be made to increase the ease, safety, and
      efficacy of epilepsy resection to improve utilization. Studies have shown an
      improved risk profile of stereoelectroencephalography (SEEG) over subdural grids
      (SDG) for invasive monitoring. One limitation to increased adoption of SEEG at
      epilepsy centers is the theoretical difficulty of planning a delayed resection
      once electrodes are removed. Our objective was to develop and present a technique
      using readily available neuronavigation technology to guide a cortical, non
      lesional epilepsy resection with co-registration of imaging during invasive
      monitoring to imaging in an explanted patient, allowing for virtual visualization
      of electrodes. METHODS: An example case taking advantage of the technique
      described above as an adjunct for an anatomically guided resection is presented
      with technical details and images. RESULTS: Intraoperative neuronavigation was
      successfully used to virtually represent previously removed SEEG electrodes and
      accuracy could be easily verified by examining scars on the scalp, bone, dura and
      pia. CONCLUSIONS: The simple technique presented can be a useful adjunct to
      resection following SEEG. This may help increase the adoption of SEEG, even when
      resection is planned.

PMID- 29461095
TI  - Differential Effects of Parental "drug talk" Styles and Family Communication
      Environments on Adolescent Substance Use.
AB  - The current study examines the relationships among adolescent reports of parent
      adolescent drug talk styles, family communication environments (e.g.,
      expressiveness, structural traditionalism, and conflict avoidance), and
      adolescent substance use. ANCOVAs revealed that the 9th grade adolescents (N =
      718) engaged in four styles of "drug talks" with parents (e.g., situated direct,
      ongoing direct, situated indirect, and ongoing indirect style) and these styles
      differed in their effect on adolescent substance use. Multiple regression
      analyses showed that expressiveness and structural traditionalism were negatively
      related to adolescent substance use, whereas conflict avoidance was positively
      associated with substance use. When controlling for family communication
      environments and gender, adolescents with an ongoing indirect style reported the
      lowest use of substance. The findings suggest implications and future directions
      for theory and practice.

PMID- 29461096
TI  - Associations Among Trajectories of Sleep Disturbance, Depressive Symptomology and
      24-Hour Urinary Cortisol in HIV+ Women Following a Stress Management
      Intervention.
AB  - OBJECTIVE: The burden of sleep disturbance and depressive symptomology is high
      for persons living with HIV and particularly so for women. While cognitive
      behavioral stress management (CBSM) is shown to reduce symptoms of depression and
      24-hr urinary free cortisol output (CORT) in HIV+ men, less is known about the
      effects of CBSM on mood and concomitant sleep disturbance in HIV+ women. The
      study aim is to model longitudinal change in sleep disturbance, depressive
      symptomology, and CORT for HIV+ women exposed to a 12-week CBSM intervention or
      control condition. METHODS: Self-reported sleep quality and depressive
      symptomology, along with CORT, was collected from surveys at baseline and
      approximately every three months thereafter for nine months from 130 HIV+ women
      (Mage = 38.44, SD = 7.73). The data was used to specify a parallel process latent
      growth model with CORT as a time-varying covariate. RESULTS: The model showed
      acceptable fit. There was a linear decline in sleep disturbance (beta = -0.32, p
      < .05) and logarithmic decline in depressive symptomology (beta = -0.33, p < .05)
      for those receiving the intervention. Decline in sleep disturbance predicted
      lower CORT at nine months. Furthermore, having less depressive symptoms at
      baseline was associated with lower initial levels of sleep disturbance and
      greater improvement in sleep quality over time. There was no discernible
      association between sleep and mood disturbance in the control group. Across
      groups, there was a consistent association between older age and greater sleep
      disturbance (r = 0.34, p < .01). CONCLUSION: Sleep disturbance appears to be a
      behavioral target for CBSM in HIV+ women although older age, preintervention
      levels of depressive mood, and time-varying levels of CORT output may limit
      improvement in sleep quality over time.

PMID- 29461098
TI  - Transcriptional regulators: valuable targets for novel antibacterial strategies.
AB  - Antibiotics have saved millions of lives over the past decades. However, the
      accumulation of so many antibiotic resistance genes by some clinically relevant
      pathogens has begun to lead to untreatable infections worldwide. The current
      antibiotic resistance crisis will require greater efforts by governments and the
      scientific community to increase the research and development of new
      antibacterial drugs with new mechanisms of action. A major challenge is the
      identification of novel microbial targets, essential for in vivo growth or
      pathogenicity, whose inhibitors can overcome the currently circulating resistome
      of human pathogens. In this article, we focus on the potential high value of
      bacterial transcriptional regulators as targets for the development of new
      antibiotics, discussing in depth the molecular role of these regulatory proteins
      in bacterial physiology and pathogenesis. Recent advances in the search for novel
      compounds that inhibit the biological activity of relevant transcriptional
      regulators in pathogenic bacteria are reviewed.

PMID- 29461099
TI  - Trends of Parent-Adolescent Drug Talk Styles in Early Adolescence.
AB  - The present study seeks to understand how parents as prevention agents approach
      substance use prevention messages during the period of early adolescence.
      Students (N = 410) in a drug prevention trial completed surveys from 7th to 9th
      grade. Using longitudinal data, a series of latent transition analyses was
      conducted to identify major trends of parent-adolescent drug talk styles (i.e.,
      never talked, situated direct, ongoing direct, situated indirect, and ongoing
      indirect) in control and treatment conditions. Findings demonstrate a
      developmental trend in drug talk styles toward a situated style of talk as youth
      transitioned from 7th grade to 9th grade. Findings also show that even though the
      drug prevention trial did not specifically target parental communication, parents
      in the treatment condition provide more ongoing substance use prevention messages
      to their adolescent children than do parents in the control condition. The
      present study discusses relevant developmental issues, potential intervention
      effects, and future research directions for communication research in substance
      use prevention.

PMID- 29461101
TI  - The Relationships Between Doctor-Patient Affectionate Communication and Patient
      Perceptions and Outcomes.
AB  - The current article combines the literature on doctor-patient communication and
      affectionate communication. Using Affection Exchange Theory (AET), the study
      predicts that the need for affection and the benefits of affectionate
      communication translate to the doctor-patient setting, proposing a series of
      relationships from both perceived doctor affectionate communication and affection
      deprivation to several patient outcome variables (patient perception of the
      doctor, patient communication with the doctor, and patient
      satisfaction/adherence). The results strongly supported the predictions for both
      affectionate communication and affection deprivation, with affectionate
      communication positively relating to most outcome measures and affection
      deprivation negatively relating to most outcome measures. Affection deprivation
      served as a moderator for the relationship between provider competence and
      patient satisfaction, although affectionate communication moderated the
      relationship between provider competence and patient adherence. Implications and
      possible directions for future research are discussed.

PMID- 29461104
TI  - Review of Fluoride Intake and Appropriateness of Current Guidelines.
AB  - Since the classical epidemiological studies by Dean, it has been known that there
      should be an optimum level of exposure to fluoride that would be able to provide
      the maximum protection against caries, with minimum dental fluorosis. The
      "optimal" daily intake of fluoride for children (0.05-0.07 mg per kilogram
      bodyweight) that is still accepted worldwide was empirically determined. In the
      present review, we discuss the appropriateness of the current guidance for
      fluoride intake, in light of the windows of susceptibility to caries and
      fluorosis, the modern trends of fluoride intake from multiple sources, individual
      variations in fluoride metabolism, and recent epidemiological data. The main
      conclusion is that it is very difficult to think about a strict recommendation
      for an "optimal" range of fluoride intake at the individual level in light of
      existing knowledge of 1) the mechanisms of action of fluoride to control caries,
      2) the mechanisms involved in dental fluorosis development, 3) the distinct
      factors that interfere in the metabolism of fluoride, and 4) the windows of
      susceptibility to both dental caries and fluorosis development. An "optimal"
      range of fluoride intake is, however, desirable at the population level to guide
      programs of community fluoridation, but further research is necessary to provide
      additional support for future decisions on guidance in this area. This list
      includes the effect of factors affecting fluoride metabolism, clinical trials on
      the effectiveness of low-fluoride dentifrices to prevent caries in the primary
      dentition, and validation of biomarkers of exposure to fluoride.

PMID- 29461105
TI  - Guidelines for Fluoride Intake: Second Discussant.

PMID- 29461102
TI  - Feedback processing in adolescents with prenatal cocaine exposure: an
      electrophysiological investigation.
AB  - Impaired cognitive control is a consequence of cocaine exposure. Difficulty with
      feedback processing may underlie this impairment. We examined neural correlates
      of feedback processing using event-related potentials (ERPs) in 49 prenatally
      cocaine-exposed (PCE) and 34 nondrug exposed (NDE) adolescents. Adolescents
      performed a reward-feedback task with win/no-win feedback in a chance-based task.
      We investigated amplitude and latency of the feedback-related negativity (FRN)
      and P300 ERP components and source-based estimates elicited during feedback
      processing. PCE adolescents had smaller P300 amplitudes for no-win feedback, and
      source analysis in the P300 time window revealed differences between groups
      localized to the dorsal anterior cingulate cortex.

PMID- 29461106
TI  - Current Guidance for Fluoride Intake: Is It Appropriate?
AB  - The purpose of this report is to examine critically the appropriateness of the
      current guidance for fluoride intake in the population (0.05-0.07 mg F/kg
      bodyweight/d), consider whether changes to the current guidance are desirable,
      and suggest further research that will strengthen the evidence base for future
      decisions on guidance/advice in this area. The benefits and the risks of using
      fluoride particularly concern preschool children because it is at this age that
      excessive fluoride intake may result in dental fluorosis. Data from mostly cross
      sectional studies show a wide variation in exposure and a considerable variation
      in the amount of fluoride ingested. Fluorosis, mostly mild, is commonly observed.
      For considering changes in current guidance, there is a need for more knowledge
      on the relationship between exposure to fluoride at an early age and the
      development of fluorosis. For that, prospective epidemiological studies with
      sufficiently large and representative samples of children are required. It is
      also important to study children in communities both with and without water
      fluoridation and to include populations where salt or milk fluoridation is used.
      There is also a need for professional agreement on acceptable levels of mild and
      moderate/severe fluorosis and a more comprehensive knowledge on the appreciation
      of mild fluorosis among the public.

PMID- 29461107
TI  - Introduction: Guidelines for Fluoride Intake-Are They Appropriate?

PMID- 29461109
TI  - Summary of General Discussion and Conclusions.

PMID- 29461108
TI  - Understanding Optimum Fluoride Intake from Population-Level Evidence.
AB  - Policy on fluoride intake involves balancing caries against dental fluorosis in
      populations. The origin of this balance lies with Dean's research on fluoride
      concentration in water supplies, caries, and fluorosis. Dean identified cut
      points in the Index of Dental Fluorosis of 0.4 and 0.6 as critical. These equate
      to 1.3 and 1.6 mg fluoride (F)/L. However, 1.0 mg F/L, initially called a
      permissible level, was adopted for fluoridation programs. McClure, in 1943,
      derived an "optimum" fluoride intake based on this permissible concentration. It
      was not until 1944 that Dean referred to this concentration as the "optimal"
      concentration. These were critical steps that have informed health authorities
      through to today. Several countries have derived toxicological estimates of an
      adequate and an upper level of intake of fluoride as an important nutrient. The
      US Institute of Medicine (IOM) in 1997 estimated an Adequate Intake (AI) of 0.05
      mg F/kg bodyweight (bw)/d and a Tolerable Upper Intake Level (UL) of 0.10 mg F/kg
      bw/d. These have been widely promulgated. However, a conundrum has existed with
      estimates of actual fluoride intake that exceed the UL without the expected
      adverse fluorosis effects being observed. Both the AI and UL need review.
      Fluoride intake at an individual level should be interpreted to inform more
      nuanced guidelines for individual behavior. An "optimum" intake should be based
      on community perceptions of caries and fluorosis, while the ultimate test for
      fluoride intake is monitoring caries and fluorosis in populations.

PMID- 29461110
TI  - Guidelines for Fluoride Intake: First Discussant.

PMID- 29461111
TI  - Executive function in middle childhood and the relationship with theory of mind.
AB  - A group of 126 typically developing children (aged 5-12 years) completed three
      cool executive function tasks (spatial working memory, stop signal, intra-extra
      dimensional shift), two hot executive function tasks (gambling, delay of
      gratification), one advanced theory of mind task (strange stories with high
      versus low affective tone), and a vocabulary test. Older children performed
      better than younger children, consistent with the protracted development of hot
      and cool executive functions and theory of mind. Multiple regression analyses
      showed that hot and cool executive functions were correlated but they predicted
      theory of mind in different ways.

PMID- 29461112
TI  - "Self" Takes it All in Mental Illness: Examining the Dynamic Role of Health
      Consciousness, Negative Emotions, and Efficacy in Information Seeking.
AB  - Mental illness such as depression, stress, and anxiety disorder is prevalent in
      our everyday lives. Yet, little is known about how health-related variables
      operate in the mental illness context. Centering on health consciousness, this
      study systematically examines how health consciousness affects information
      seeking and whether negative emotions and efficacy intervene in the relationship
      in mental illness. The results of the survey (N = 614) suggest that health
      consciousness relates to fear, anxiety, self-efficacy, and response efficacy but
      does not relate to information seeking. Interestingly, self-efficacy is the only
      mediator in the relationship between health consciousness and information seeking
      on mental illness. Implications are discussed.

PMID- 29461113
TI  - Beyond Adjustment: Authoring a (Re)learned Reality.
AB  - A survivor of a traumatic brain injury makes sense of his injury and reflects on
      the unique individuality of injury.

PMID- 29461114
TI  - Picture Yourself Healthy-How Users Select Mediated Images to Shape Health
      Intentions and Behaviors.
AB  - Hypotheses on how selective viewing of mediated images may sustain eating habits
      and aid healthier eating were derived from the Selective Exposure Self- and
      Affect Management model. The model posits that individuals select to view media
      to manage their self-concepts-and that this exposure affects subsequent
      intentions and behaviors. Participants (N = 265) selectively viewed Instagram
      like postings featuring healthy or unhealthy food imagery. Beforehand,
      participants reported habits and perceived expert recommendations regarding food
      intake. After viewing postings, participants chose gift cards representing
      healthy or unhealthy food purchases and indicated food intake intentions. Results
      show that existing eating behavior predicts selective exposure to healthy or
      unhealthy food imagery, which in turn shapes gift card choices and (both healthy
      and unhealthy) food intake intentions.

PMID- 29461118
TI  - Emotional face recognition in individuals withattention-deficit/hyperactivity
      disorder: a review article.
AB  - This review focuses on facial emotion recognition (FER) in individuals with
      attention- deficit/hyperactivity disorder (ADHD). Behavioral studies of FER in
      ADHD have resulted in inconsistent findings. Here, we discuss the factors that
      vary across studies and the way that they influence FER processes in ADHD. Across
      reviewed studies, fear was the most deficient facial expression to be recognized.
      Our review suggested that FER deficit in ADHD does not alleviate across
      development and is partially distinct from ADHD symptoms. In conclusion,
      assessment of FER in ADHD and targeting that in interventional plans could lead
      to social skills improvement in ADHD.

PMID- 29461119
TI  - Reconsidering the relation between serum homocysteine and red blood cell
      distribution width: a cross-sectional study of a large cohort.
AB  - PURPOSE: In a recent small sample study, red blood cell distribution width (RDW)
      was suggested as a predictor of homocysteine levels. The current study was aimed
      to reexamine this association in a large scale sample. METHODS: A retrospective
      cross-sectional study of healthy adults, conducted at Rabin Medical Center,
      during 2000-2014. Data were retrieved from the medical charts and a logistic
      regression controlling for interfering factors was carried out. Sensitivity
      analysis was implemented by exclusion of individuals with anaemia. RESULTS: Five
      thousand, five hundred fifty-four healthy individuals were included. Mean serum
      homocysteine level was 10.10 (SD 2.72) MUmol/L. 34.4% of the study population had
      a homocysteine level higher than the upper limit of normal (10.8 MUmol/L).
      Homocysteine showed no association with RDW (OR 1.00; 95% CI 0.97-1.03), but
      increased with age (OR 1.05; 95% CI 1.04-1.06) and decreased with a rise in
      haemoglobin (OR 0.77; 95% CI 0.71-0.83), and in the mean corpuscular volume (OR
      0.86; 95% CI 0.85-0.88). Exclusion of individuals with anaemia did not reveal an
      association between homocysteine and RDW but found a somewhat smaller association
      between haemoglobin and RDW [OR 0.82; 95% CI 0.73-0.91]. CONCLUSIONS: In our
      large scale sample we did not find an association between RDW and serum
      homocysteine.

PMID- 29461121
TI  - Topical 3% tranexamic acid enhances the efficacy of 1064-nm Q-switched neodymium
      doped yttrium aluminum garnet laser in the treatment of melasma.
AB  - BACKGROUND: A QS-NdYAG laser (QSNYL) and topical tranexamic acid (TA) have been
      widely used. However, no study has yet reported the efficacy of using both QSNYL
      and TA as a combined treatment for melasma. OBJECTIVES: To evaluate the efficacy
      and adverse effects of topical 3% TA combined with 1064-nm QSNYL as a treatment
      for melasma. METHODS: A randomized, prospective, split-face, controlled trial was
      conducted. A 1064-nm QSNYL was performed on the entire face at baseline and 4
      weeks later. The participants were randomly selected for application of topical
      3% TA on one side of the face and the vehicle treatment on the other side of the
      face for 8 weeks. Clinical responses were determined by mMASI scores,
      MexameterTM, and participants' evaluation. RESULTS: Twenty-five participants
      completed the study. At the end of the study, the mMASI score significantly
      decreased in the combination treatment (p < 0.05), while no significant changes
      were observed in the laser-alone treatment. More than 80% of the participants
      noticed a >50% improvement on the side with combination therapy at every follow
      up visit. No serious adverse events were reported. CONCLUSION: Topical TA as an
      adjuvant demonstrated trends of better outcomes than QSNYL alone for the
      treatment of melasma.

PMID- 29461120
TI  - Follicle-stimulating hormone peptide-conjugated nanoparticles for targeted shRNA
      delivery lead to effective gro-alpha silencing and antitumor activity against
      ovarian cancer.
AB  - The distinct hormone molecules and receptors, such as follicle-stimulating
      hormone receptor (FSHR) in ovarian cancer, provide opportunities for more
      precisely targeted therapy. We previously developed FSHR-mediated nanoparticles
      and found that FSH peptides on the surface of nanoparticles improved the delivery
      of short interfering RNA (siRNA) into ovarian cancer cells. However, the high
      toxicity of the nanoparticles and the transient silencing of the siRNA in vivo
      limited further study. Here, we developed FSH peptide-conjugated nanoparticles
      with an increased amount of polyethylene glycol (PEG) grafting and encapsulated
      short hairpin RNA (shRNA) to silence the target gene, growth-regulated oncogene
      alpha (gro-alpha). The nanoparticle complexes exhibited good stability over three
      weeks. Expression of the target gene, gro-alpha, was significantly down-regulated
      by gro-alpha shRNA-loaded nanoparticles conjugated with FSH peptides (FSH33-G-NP)
      in FSHR-positive HEY cells. Cell proliferation, migration, and invasion were also
      inhibited by FSH33-G-NP. Tumor growth was delayed significantly in the mice
      treated with FSH33-G-NP. No significant loss of body weight or severe toxic
      effects were observed in any groups. In conclusion, gro-alpha shRNA-loaded
      nanoparticles conjugated with FSH peptides overcame the drawbacks of the in vivo
      application of RNAi therapeutics and polymer-based nanocarriers and showed safe
      antitumor efficacy. Our study might contribute to the application of FSHR-based
      targeted therapy and imaging in cancer.

PMID- 29461123
TI  - Correction to: Shu, et al., HIV/AIDS-related hyponatremia: an old but still
      serious problem.

PMID- 29461125
TI  - The long-term effect of pulsed dye laser on Necrobiosis Lipoidica: A case study.
AB  - A 57-year-old female was presented with an irrepressible case of Necrobiosis
      Lipoidica considering the possibility of a surgical skin graft. Instead, a pulsed
      dye laser treatment was used as an alternate treatment. Previous case studies
      have been found in the literature on the effect of pulsed dye laser on
      Necrobiosis Lipoidica. The use of a pulsed dye laser in this case resulted in
      rendering the lesions asymptomatic for pain and a reduction in volume. Prolonged
      control was exhibited. From this case, we conclude that pulsed dye laser therapy
      is effective when increasing the number of treatments of laser therapy, and can
      be used as a treatment for Necrobiosis Lipoidica.

PMID- 29461124
TI  - Improving mandibular contour: A pilot study for indication of PPLA traction
      thread use.
AB  - BACKGROUND: The request for less-aggressive procedures to improve mandibular
      contour is increasing. Several kinds of threads have been used for this purpose.
      Nevertheless, PLLA (poly-L-Lactic acid) traction thread procedure has not been
      previously described. AIM: To investigate the role of PLLA traction threads in
      improving mandibular contour. METHODS: Twenty women were enrolled in the study.
      They were differentially classified for skin laxity. Patients were treated in a
      single session with two PLLA traction threads per side. Specific post-procedure
      instructions were given to patients, and complications occurred after the
      procedures were estimated. A Fisher's t-test was performed to identify criteria
      related to longevity of results. RESULTS: We found longevity of results to be
      associated with younger age (p = 0.001), absence of severe skin laxity of jawline
      and neck (p = 0.001), and aesthetic satisfaction (p = 0.024). Edema, swelling,
      and temporary skin contour irregularities were found in most cases (N = 16; 80%),
      whereas paresthesia resolving without sequelae in 2-4 weeks was found in two
      cases (10%). CONCLUSIONS: Our results show that selected patients, younger than
      51 and showing a mild-moderate degree of skin laxity of jawline and neck angle
      represent ideal candidates for PLLA traction thread treatment. Further studies
      will be performed to confirm our results.

PMID- 29461122
TI  - Synchronous delivery of oxygen and photosensitizer for alleviation of hypoxia
      tumor microenvironment and dramatically enhanced photodynamic therapy.
AB  - Photosensitizer, proper laser irradiation, and oxygen are essential components
      for effective photodynamic therapy (PDT) in clinical cancer therapy. However,
      native hypoxic tumoral microenvironment is a major barrier hindering photodynamic
      reactions in vivo. Thus, we have prepared biocompatible liposomes by loading
      complexes of oxygen-carrier (hemoglobin, Hb) and photosensitizer (indocyanine
      green, ICG) for enhanced PDT against hypoxic tumor. Ideal oxygen donor Hb, which
      is an oxygen-carried protein in red blood cells, makes such liposome which
      provide stable oxygen supply. ICG, as a photosensitizer, could transfer energy
      from lasers to oxygen to generate cytotoxic reactive oxygen species (ROS) for
      treatment. The liposomes loading ICG and Hb (LIH) exhibited efficient tumor
      homing upon intravenous injection. As revealed by T2-weighted magnetic resonance
      imaging and immunohistochemical analysis, the intratumoral hypoxia was greatly
      alleviated, and the level of hypoxia inducible factor-1alpha (HIF-1alpha) and
      vascular endothelial growth factor (VEGF) in tumor was obviously down-regulated.
      A weak PDT efficiency was found in cells incubated in simulated hypoxia condition
      in vitro, while PDT effect was dramatically enhanced in LIH treated hypoxia cells
      under near-infrared (NIR) laser, which was mainly attributed to massive
      generation of ROS with sufficient oxygen supply. ROS trigger oxidative damage of
      tumors and induce complete suppression of tumor growth and 100% survival rate of
      mice, which were also in good health condition. Our work highlights a liposome
      based nanomedicine that could effectively deliver oxygen to tumor and alleviate
      tumor hypoxia state, inducing greatly improved efficacy compared to conventional
      cancer PDT and demonstrates the promise of modulating unfavorable tumor
      microenvironment with nanotechnology to overcome limitations of cancer therapies.

PMID- 29461126
TI  - Network and Individual Factors Associated with Drug Use among Female Sex Workers
      (FSWs) in Southern China: A Mixed-Method Approach.
AB  - Research on women who engage both in drug use and sex work has been limited, as
      most previous studies have focused on these risk behaviors separately. The
      current study examines the network properties as well as the demographic and
      behavioral factors associated with drug use among female sex workers (FSWs) in
      southern China. We collected survey data (n = 175) in the Hainan province during
      our 26 months of ethnographic fieldwork in China. Our analyses included Fisher's
      exact chi-square tests, independent-samples t-tests, Mann-Whitney U, binary
      logistic regression (LR), as well as ethnographic data analysis. Multivariate
      analysis showed that women who were younger age, single, more educated, and
      earning a higher income were more likely to use drugs. Pertaining to network
      properties, FSWs with a lower percentage of long-term clients (and men) in ego
      networks were more likely to use drugs; this would imply a mechanism by which
      drug-using FSWs are more at risk, as the women take a greater number of transient
      clients. In addition, FSWs who were influential network members (i.e., higher
      betweenness centrality) and were closely related to other network members (i.e.,
      higher closeness centrality) were more likely to use drugs; this may suggest that
      drug use is a means of sustaining the high functionality of the workers. Our
      ethnographic data also showed that club drug use was easily accessible in
      entertainment venues and was often a means of socialization in FSW communities.
      Network characteristics correlated to HIV-related risks among FSWs should be
      further examined in future studies.

PMID- 29461127
TI  - MIBI scintigraphy of parathyroid adenomas: correlation with biochemical and
      histological markers.
AB  - PURPOSE: In this study, we tested the hypothesis that MIBI-positive and MIBI
      negative adenomas of parathyroid glands (APGs) have distinct biochemical and
      histological markers that could help differentiate MIBI-positive from MIBI
      negative APGs. PATIENTS AND METHODS: 40 patients with 41 APGs were included in
      the study. Patients were enrolled in the study after MIBI scintigraphy
      examinations had been carried out. Biochemical analyses included serum levels of
      calcium (Ca), intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D3 (25-OH
      D3). All patients had neck ultrasound and MIBI examinations. After surgical
      resection the APGs were examined histologically. RESULTS: In each of 39 patients
      one APG could be confirmed by histology, and in one patient, two contralateral
      APGs were identified. MIBI studies were positive in 73 % and negative in 27 % of
      the APGs. False-positive cases were not observed. MIBI-negative APGs were only
      present in patients with iPTH values below 150 pg/ml. In 82 % of MIBI negative
      studies oxyphilic cells were absent, and this cell type was present in only 18 %
      of MIBI negative cases (p < 0.001). Regarding cysts within the APGs, no
      differences were demonstrated between MIBI positive or negative studies (p =
      0.32). Fat cells were seen in none of the MIBI -negative studies and in only 3 %
      of MIBI positive studies (p = 0.08). CONCLUSIONS: For APGs, MIBI positivity
      correlates with serum iPTH concentration. The absence of oxyphilic cells with
      large numbers of mitochondria in APGs contributes to MIBI negativity, probably
      because of the reduced binding sites for the radiotracer.

PMID- 29461128
TI  - Ocular complications after cosmetic periocular diode laser application to the
      eyelids.
AB  - A 25-year-old woman underwent diode laser application on the both upper eyelids
      in the dermatology department of a private hospital to obtain a cosmetic healing
      of the reddish look on her eyelids without any protective lenses. The patient
      experienced severe uveitis, atonic pupils, raised intraocular pressure, and
      increased sensitivity to light in her eyes on the following day of the procedure.
      Topical steroids and pressure-lowering agents were able to treat the acute
      uveitis and glaucoma, unfortunately the patient suffered from irreversible atonic
      and atrophic pupils and photosensitivity. It is recommended that cosmetic laser
      application on the periocular area should be avoided, and if it is still to be
      performed, it should be applied cautiously and the patient should be informed of
      the potential ocular complications.

PMID- 29461129
TI  - Functioning and primary healthcare utilization in older adults: a 1-year follow
      up study.
AB  - BACKGROUND/PURPOSE: Older adults are high users of healthcare services, mainly
      due to health conditions and their impact on daily activities, challenging the
      ability of health systems to provide timely and high-quality care. Conceivably,
      using disability-related variables to predict future healthcare utilization could
      contribute to reduce both older adults' disability and healthcare costs. This
      study aimed to explore the association between aspects of disability and older
      adults' primary healthcare utilization and hospitalization over a period of 1
      year. METHODS: Older adults (n = 129) were assessed for self-reported disability,
      lower limb performance, pain intensity and number of painful body sites,
      depressive symptoms, and self-reported physical activity. Data on primary
      healthcare utilization and hospitalization were collected for the period of 1
      year through registries and phone interviews. RESULTS: Regression analysis,
      adjusted for potential confounders, showed that self-reported disability and pain
      intensity were significantly associated with total primary healthcare utilization
      and together with a confounding variable (number of chronic conditions) explained
      16% of its variance (p < 0.05). Increased physical activity was significantly
      associated with a decreased likelihood of being admitted to hospital (95% CI for
      exponentiation (B) = 0.27-0.81). DISCUSSION: Data suggest that decreasing self
      reported disability and increasing physical activity may decrease primary
      healthcare utilization and hospitalization, respectively.

PMID- 29461130
TI  - Treatment of facial telangiectasia with narrow-band intense pulsed light in
      Chinese patients.
AB  - OBJECTIVE: To evaluate the efficacy and safety of narrow-band intense pulsed
      light (DPL) in treating facial telangiectasia. METHOD: Thirty patients with
      facial telangiectasia underwent five sessions of treatment with DPL (500 nm~600
      nm) at 4-week interval. The erythema index (EI), temperature, transepidermal
      water loss (TEWL), and lightness of the skin (L) were measured before each
      treatment session and at each follow-up. RESULT: Thirty cases completed treatment
      and follow-ups. Twenty-seven cases (90%) got more than 50% clearance post
      treatment and among them eight cases (27%) got more than 75% clearance. The
      average of the mean EI value decreased with the number of treatment sessions; the
      EI observed after two treatment sessions was significantly different from that
      observed before treatment (P = 0.012, P < 0.05). The decrease in skin temperature
      and TEWL values post-treatment was statistically significant (P = 0.000, P =
      0.027, P < 0.05), while the L value increased significantly (P = 0.025, P <
      0.05). Thirty percent cases had reccurence at 6-month follow-up. While burning
      sensation, erythema, and swelling were usually seen during the treatment, no
      severe side effects were observed during treatment and follow-ups. CONCLUSION:
      Narrow-band intense pulsed light DPL is effective and safe in treating facial
      telangiectasia.

PMID- 29461131
TI  - Interprofessional transformation of clinical education: The first six years of
      the Veterans Affairs Centers of Excellence in Primary Care Education.
AB  - This paper describes the Centers of Excellence in Primary Care Education
      (CoEPCE), a seven-site collaborative project funded by the Office of Academic
      Affiliations (OAA) within the Veterans Health Administration of the United States
      Department of Veterans Affairs (VA). The CoEPCE was established to fulfill OAA's
      vision of large-scale transformation of the clinical learning environment within
      VA primary care settings. This was accomplished by funding new Centers within VA
      facilities to develop models of interprofessional education (IPE) to teach health
      professions trainees to deliver high quality interprofessional team-based primary
      care to Veterans. Using reports and data collected and maintained by the National
      Coordinating Center over the first six years of the project, we describe program
      inputs, the multicomponent intervention, activities undertaken to develop the
      intervention, and short-term outcomes. The findings have implications for lessons
      learned that can be considered by others seeking large-scale transformation of
      education within the clinical workplace and the development of interprofessional
      clinical learning environments. Within the VA, the CoEPCE has laid the foundation
      for IPE and collaborative practice, but much work remains to disseminate this
      work throughout the national VA system.

PMID- 29461132
TI  - Heavy Alcohol Use Among Migrant and Non-Migrant Male Sex Workers in Thailand: A
      Neglected HIV/STI Vulnerability.
AB  - BACKGROUND: There is scarce research on male sex workers in the context of
      alcohol use. While heavy alcohol use has been established as a risk factor for
      HIV and STI infections among men who have sex with men (MSM), men who engage in
      sex work with other men, particularly from the Global South, have not been
      included in these studies. Moreover, studies among male sex workers in Asia often
      do not explore migration contexts of these men. OBJECTIVES: The objective of this
      exploratory study is to examine the prevalence and correlates of heavy alcohol
      use among migrant and non-migrant male sex workers in Bangkok and Pattaya,
      Central Thailand. METHODS: Between August and October 2015, 18-24 year-old
      migrant and non-migrant male sex workers (n = 212) were recruited from various
      male sex work-identified venues (bars, clubs, massage parlors, and go-go bars) to
      take an interviewer-administered cross-sectional survey in Bangkok and Pattaya,
      Thailand. Measures were adapted from previous studies in similar populations and
      included structured questions across four domains, including demographic
      characteristics, alcohol use, stimulant use, and sexual behaviors. Multivariable
      logistic regression assessed the independent associations between heavy alcohol
      use (heavy versus not heavy) and demographic characteristics, stimulant use and
      sexual behavior. RESULTS: Heavy alcohol use was prevalent among one-third of
      participants. Heavy alcohol use was positively associated with male sex workers
      who were non-migrant and Thai, currently using stimulants, having 15 or more male
      clients in the past month and having first consumed alcohol at age 15 years or
      younger. CONCLUSIONS: Current HIV prevention efforts should consider
      subpopulations of MSM, including male sex workers and migrants, as well as other
      risk behaviors like alcohol, as important contexts for HIV and STI risks.

PMID- 29461133
TI  - Natural options for management of melasma, a review.
AB  - A blemish free, even-toned skin is universally associated with healthy skin. This
      reasoning makes people desire to have a flawless skin. Melanin is a naturally
      occurring pigment in humans. This pigment is responsible for skin, hair, and eye
      color, therefore determines our race and phenotypic appearance. On darker skin
      types, it is common that melanin production processes malfunctions. These
      malfunctions often lead to overproduction and secretion of melanin. As a result,
      unwanted pigmentary problems such melasma occur. Due to unknown etiology and its
      recurrence in nature, melasma is challenging to treat. The current available
      melasma treatment options often produce undesired side effects and suboptimum
      results. First-line topical treatments usually involve hydroquinone or topical
      steroids. Apart from the irritant reactions, this treatment mode is not suitable
      for all skin types. Skin care specialists are in search of an effective long-term
      cosmetics and cosmeceuticals to address hypermelanosis problems. Understanding of
      naturally occurring depigmenting agents provides an opportunity for more
      effective ways to manage melasma in all skin types. This review considers the
      benefits of naturally occurring ingredients which could help address skin
      pigmentation problems and broaden the choice for skin-lightening treatments.

PMID- 29461134
TI  - Correlates of Validity of Self-Reported Methamphetamine Use among a Sample of
      Dependent Adults.
AB  - BACKGROUND: Self-reported data are widely used in substance-use research, yet few
      studies have assessed the validity of self-reported methamphetamine use compared
      to biological assays. OBJECTIVES: We sought to assess the validity and correlates
      of validity of self-reported methamphetamine use compared to urine toxicology
      (UTOX). METHODS: Using a sample of methamphetamine-dependent individuals enrolled
      in a randomized controlled pharmacotherapy trial in the United States (n = 327
      visits among 90 participants), we calculated sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), and the kappa
      coefficient of self-reported methamphetamine use in the past 3 days compared to
      UTOX, as well as the NPV of self-reported methamphetamine use over an extended
      recall period of 1 month. We used multivariable logistic regression models to
      assess correlates of concordance between self-reported methamphetamine use and
      UTOX. RESULTS: The sensitivity of self-reported methamphetamine use in the past 3
      days was 86.7% (95% confidence intervals (95%CI): 81.4%-91.4%), the specificity
      was 85.3% (77.7-91.3), the PPV was 91.5% (86.9-94.8), and the NPV was 78.0% (69.4
      86.1), compared to UTOX (kappa = 0.71). The NPV over the extended recall period
      was 70.6% (48.0-85.7). In multivariable analyses, validity of self-reported
      methamphetamine use was higher for older participants but lower during follow-up
      compared to baseline and when polysubstance use or depressive symptoms were
      reported. Conclusions/Importance: Our sample of methamphetamine-dependent adults
      reported recent methamphetamine use with high validity compared to UTOX. Validity
      increased with age but decreased when participants reported depressive symptoms
      or polysubstance use as well as later in the study timeline and during longer
      recall periods.

PMID- 29461135
TI  - Teamwork and Adherence to Recommendations Explain the Effect of a Care Pathway on
      Reduced 30-day Readmission for Patients with a COPD Exacerbation.
AB  - This study aimed to increase our understanding of processes that underlie the
      effect of care pathway implementation on reduced 30-day readmission rate.
      Adherence to evidence-based recommendations, teamwork and burnout have previously
      been identified as potential mechanisms in this association. We conducted a
      secondary data analysis of 257 patients admitted with chronic obstructive
      pulmonary disease exacerbation and 284 team members caring for these patients in
      19 Belgian, Italian and Portuguese hospitals. Clinical measures included 30-day
      readmission and adherence to a specific set of five care activities. Teamwork
      measures included team climate for innovation, level of organized care and
      burnout (emotional exhaustion, level of competence and mental detachment). Care
      pathway implementation was significantly associated with better adherence and
      reduced 30-day readmission. Better adherence and higher level of competence were
      also related to reduced 30-day readmission. Only better adherence fully mediated
      the association between care pathway implementation and reduced 30-day
      readmission. Better team climate for innovation and level of organized care,
      although both improved after care pathway implementation, did not show any
      explanatory mechanisms in the association between care pathway implementation and
      reduced 30-day readmission. Implementation of a care pathway had an impact on
      clinical and team indicators. To reduce 30-day readmission rates, in the
      development and implementation of a care pathway, hospitals should measure
      adherence to evidence-based recommendations during the whole process, as this can
      give information regarding the success of implementation.

PMID- 29461136
TI  - Working With Clients With Limited English Proficiency: Mapping Language Access in
      Occupational Therapy.
AB  - Nearly one in ten US residents have difficulty speaking and understanding English
      and are deemed to have limited English proficiency (LEP). Despite federal
      mandates for provision of interpreters and other language access services,
      individuals with LEP experience notable health disparities. Occupational
      therapists must be prepared to equitably serve this population, however there is
      a dearth of research evidence and practical recommendations about our
      profession's readiness to serve this growing population. This paper maps the
      current healthcare policy environment and existing language access research
      relevant to occupational therapy. Implications for the future of occupational
      therapy research, education and practice are discussed.

PMID- 29461137
TI  - Getting on the same page: an interprofessional common reading program as
      foundation for patient-centered care.
AB  - A primary goal of interprofessional education is to produce clinicians who
      practice collaboratively to provide patient-centered care. This exploratory study
      evaluated whether students' attitudes about a literary account of an illness
      experience endured after a year of professional and clinical education and if
      students applied lessons learned from a common reading to the delivery of patient
      centered care. Six focus groups were completed with health professions students
      and five main themes emerged from the focus group data. Themes include: Seeing
      family members as stakeholders; Establishing common ground with peers and the
      larger reason for graduate school; Applying lessons to clinical practice that see
      the patient as a person; Experiencing an emotional connection with a story and
      its characters; and Taking alternative perspectives/stepping into the shoes of
      the patient. Study results are discussed in relation to the interprofessional
      education literature, with implications for educators and interprofessional
      curricula also presented. We conclude that a common reading program may provide
      an effective means for developing health professions students' knowledge and
      attitudes in the tenets of patient-centered collaborative care. It has the
      potential to build community through shared intellectual experience, facilitating
      meaningful reflection and perspective-taking in interprofessional learners.

PMID- 29461138
TI  - Enablers and barriers to the development of interprofessional collaboration
      between physicians and osteopaths: A mixed methods study.
AB  - Osteopathy is a complementary and alternative medicine (CAM) that is growing in
      popularity. Increasing numbers of parents are seeking pediatric osteopathic care
      in addition to conventional medical care. Information about the development of
      interprofessional collaboration (IPC) between these practitioners is scarce. This
      explanatory sequential mixed methods study aimed to explore enablers of and
      barriers to the development of IPC between physicians and osteopaths involved
      with pediatric patients in primary care in Quebec, Canada. Postal questionnaires
      about collaborative practices were first sent to all physicians and osteopaths
      working with pediatric patients in Quebec. Semi-structured individual interviews
      were then conducted with a subset of 10 physicians and 11 osteopaths. A total of
      274 physicians (14%) and 297 osteopaths (42%) completed the survey. Forty-five
      percent (n = 122) of physicians reported that they referred at least one
      pediatric patient per month to an osteopath. Thirty-six percent (n = 96) of
      physicians and 41% (n = 122) of osteopaths indicated having professional
      relationships. Personal consultation, professional relationship, perceived
      utility of osteopathy and community practice were positively associated with
      osteopathic referrals. According to participants, the strongest enabler of the
      development of collaboration was positive clinical results reported by parents.
      Additional enablers included the osteopath having previous health professionals
      training such as physiotherapist, pediatric experience, mutual respect for
      professional boundaries and complementarity, perceived safety of osteopathy, and
      parents' requests for collaboration. Barriers were the absence of a common
      language, the organizational and legal context, uncertainty regarding one
      another's roles, lack of interprofessional interactions, and limited scientific
      evidence. These results related to enablers of and barriers to collaboration
      between physicians and osteopaths and the illustration of their dynamic
      interaction could be used to guide efforts to promote productive collaboration
      and safe patient-oriented care.

PMID- 29461139
TI  - Placebo effect of facilitatory Kinesio tape on muscle activity and muscle
      strength.
AB  - PURPOSE: Kinesio tape (KT) is claimed to be able to facilitate muscle activation
      and promote muscle strength. Previous studies have proposed that placebo effect
      could be a major attributing factor. This study sought to compare the effects of
      facilitatory KT on muscle activity and performance between regular KT-users and
      non-users. METHODS: Sixty participants, including 27 regular KT-users and 33 non
      users, performed maximal grip assessment with and without facilitatory KT, which
      was applied to their wrist extensor muscles of the dominant forearm from the
      direction of origin to insertion at 75% of its maximal tension. Within-subject
      comparisons of normalized root mean square of the wrist extensors
      electromyographic activity, maximal grip strength, and perceived performance were
      conducted. RESULTS: KT-users showed an increase in grip strength with application
      of facilitatory KT, when compared to tapeless condition (p = 0.030, Cohen's d =
      0.16). Non-users demonstrated similar grip strength with and with KT application
      (p = 0.232). No significant differences were found in the muscle activity (p >
      0.198) and perceived performance (p > 0.400) in both groups. CONCLUSIONS:
      Facilitatory KT promotes maximal grip strength only among regular KT users, but
      its effect is trivial. Interestingly, such effect is not related to any
      electrophysiological change in the KT applying muscle, which may indicate an
      indirect working mechanism leading to the increased grip strength.

PMID- 29461140
TI  - Genetic investigation of ocular developmental genes in 52 patients with
      anophthalmia/microphthalmia.
AB  - BACKGROUND: Mutation in eye developmental genes has been reported to cause
      anophthalmia and microphthalmia. However, in India, especially in the Western
      Indian population, such reports are scarce. Hence, the present study aims to
      investigate mutations in 15 ocular developmental genes in patients with
      anophthalmia and microphthalmia in the western region of India. MATERIALS AND
      METHODS: Genomic DNA was isolated from the blood of 52 individuals affected with
      microphthalmia and anophthalmia, and 50 healthy normal controls. Polymerase chain
      reaction (PCR) was carried out for 15 genes including BMP4, CRYBA4, FOXE3, GDF6,
      GJA3, GJA8, MITF, OTX2, PAX6, PITX3, RAX, SIX3, SIX6, SOX2, and VSX2 using gene
      specific primers spanning the exon-intron boundaries and part of a promoter
      region. The amplified PCR products were purified and then subjected to Sanger's
      bi-directional sequencing. Nucleotide variations were examined using a basic
      local alignment search tool (BLAST). RESULTS: Bi-directional sequencing
      identified 8 novel and 14 known variations. Out of this, the variations GJA3
      c.92T>A; p.Ile31Asn, SOX2-c.542C>A; p.Pro181Gln and SOX2-c.541_542delinsGA;
      p.Pro181Glu were found to be deleterious by in silico analysis. The GJA3
      p.Ile31Asn mutation was identified in a patient with bilateral microphthalmia,
      microcornea, and membranous cataract. The SOX2-p.Pro181Gln and SOX2-p.Pro181Glu
      mutations were identified in patients with isolated bilateral microphthalmia and
      microphthalmia with microcornea, respectively. A novel nondeleterious missense
      variation was identified in the GJA8 gene in a patient with anophthalmia.
      CONCLUSION: These results support the crucial role of GJA3 and SOX2 in eye
      development and indicate a detailed functional study to understand the molecular
      mechanisms underlying the disease pathology.

PMID- 29461141
TI  - Additional arguments supporting that Franklin Delano Roosevelt's paralytic
      illness was related to Guillain-Barre syndrome.

PMID- 29461142
TI  - Reweighting anthropometric data using a nearest neighbour approach.
AB  - When designing products and environments, detailed data on body size and shape
      are seldom available for the specific user population. One way to mitigate this
      issue is to reweight available data such that they provide an accurate estimate
      of the target population of interest. This is done by assigning a statistical
      weight to each individual in the reference data, increasing or decreasing their
      influence on statistical models of the whole. This paper presents a new approach
      to reweighting these data. Instead of stratified sampling, the proposed method
      uses a clustering algorithm to identify relationships between the detailed and
      reference populations using their height, mass, and body mass index (BMI). The
      newly weighted data are shown to provide more accurate estimates than traditional
      approaches. The improved accuracy that accompanies this method provides designers
      with an alternative to data synthesis techniques as they seek appropriate data to
      guide their design practice.Practitioner Summary: Design practice is best guided
      by data on body size and shape that accurately represents the target user
      population. This research presents an alternative to data synthesis (e.g.
      regression or proportionality constants) for adapting data from one population
      for use in modelling another.

PMID- 29461143
TI  - ?

PMID- 29461144
TI  - ?

PMID- 29461145
TI  - ?

PMID- 29461146
TI  - ?

PMID- 29461147
TI  - ?

PMID- 29461148
TI  - ?

PMID- 29461149
TI  - ?

PMID- 29461150
TI  - ?

PMID- 29461151
TI  - ?

PMID- 29461152
TI  - Evaluating the Emotional Impact of Warning Images on Young Adult Smokers and
      Susceptible Non-Smokers.
AB  - On-pack tobacco warnings typically feature long-term health risks, which many
      young adults rationalize or reject. We examined the emotions generated by more
      proximal warnings to see if we could identify common features among the most
      effective warnings. Respondents in a sample of 474 smokers and 476 susceptible
      non-smokers used a modified Geneva Emotion Wheel (GEW) to assess cigarette packs
      displaying 12 test warnings and one current warning. The strongest emotions
      aroused in smokers were disgust, disappointment, and regret. Three warnings
      showing the effect of smoking on babies and animals had significantly higher
      emotional potency scores than a current health warning. Among susceptible non
      smokers, warnings showing harm to animals, child labor, and a dying smoker had
      the highest emotional potency. Stronger negative emotions were elicited from both
      smokers and susceptible non-smokers by warnings that featured more proximal
      outcomes than are typically shown in on-pack tobacco warnings. On-pack warnings
      that resonate with young people, the group most at risk of smoking and most
      likely to benefit from quitting, could promote cessation and deter initiation
      more effectively than warnings depicting long-term health outcomes. The GEW could
      be used to screen potential warning images to identify those most likely to be
      worth evaluating.

PMID- 29461153
TI  - The Role of Masculinity and Depressive Symptoms in Predicting Suicidal Ideation
      in Homeless Men.
AB  - Men's suicide rates may be influenced by difficulties recognizing externalizing
      depressive symptoms in men that adhere to hegemonic masculine gender role norms.
      The purpose of this study was to investigate the ability of externalizing
      depressive symptoms, internalizing depressive symptoms, and hegemonic masculinity
      in predicting the existence and severity of suicidal ideation. Homeless men (n =
      94) completed questionnaires at a resource center in the Rocky Mountain Western
      United States. Internalizing symptoms predicted the existence of suicidal
      ideation, and both externalizing and internalizing symptoms predicted increased
      severity of suicidal ideation. The masculine norms violence and playboy were
      correlated with men's suicidal ideation. An externalizing-internalizing model of
      predicting suicide in men and men's adherence to certain masculine gender role
      norms may be valuable to further efforts in suicide assessment and prevention.

PMID- 29461154
TI  - Thomas Secker M.D.: Archbishop and man-midwife.
AB  - This paper provides a biographical outline of the career of Thomas Secker, MD,
      who from 1758-68 was Archbishop of Canterbury. Although much has been written on
      Secker, this study seeks to highlight his training in medicine, which has been
      largely overlooked hitherto by historians.

PMID- 29461155
TI  - Cut stroke in half: Polypill for primary prevention in stroke.
AB  - This review summarizes the potential for polypill therapies for stroke
      prevention. While a number of studies applying different approaches regarding
      polypill have been performed, none of them has had a focus on stroke as the main
      outcome. A combination pill containing drugs such as statins, diuretics, and
      other antihypertensives is currently available in various formats. Estimates
      focusing mostly on primary prevention show that using such a combination drug a
      reduction in the 5-year stroke incidence by 50% can be achieved - especially in
      low- and middle-income countries with a high prevalence of risk factors even
      among people at young ages. A combination of a large supporting population-wide
      program with a registry-based quality control is the most likely perspective and
      can be achieved within a reasonable time frame and potentially have significant
      influence in young stroke populations.

PMID- 29461156
TI  - Pathology in Practice.

PMID- 29461157
TI  - Safety of vitamin K, and its use in pet foods.

PMID- 29461158
TI  - Use of endoscopic-guided electrocautery ablation for treatment of tracheal
      liposarcoma in a dog.
AB  - CASE DESCRIPTION A 7-year-old 44-kg (97-lb) neutered male Great Pyrenees was
      referred for evaluation because of episodic dyspnea with cyanosis of 1 to 2
      weeks' duration. Three days prior to evaluation, the clinical signs had worsened,
      including 1 episode of collapse. CLINICAL FINDINGS Thoracic radiography and CT
      revealed a well-delineated soft tissue mass, located approximately 1.5 cm cranial
      to the carina and occupying almost 90% of the tracheal lumen. A CBC and serum
      biochemical analysis were performed, and all results were within reference
      limits. TREATMENT AND OUTCOME Tracheoscopy confirmed the presence of a broad
      based bilobate mass that was protruding from the right dorsal aspect of the
      trachea and occupied almost the entire tracheal lumen. The mass was successfully
      resected by endoscopic-guided electrocautery ablation. Findings of histologic
      evaluation were consistent with a diagnosis of liposarcoma. Immediately following
      the ablation procedure, the previously noted clinical signs of respiratory tract
      disease resolved. On follow-up examination 12 months later, no regrowth of the
      mass was evident on thoracic helical CT and tracheoscopy. CLINICAL RELEVANCE
      Endoscopic-guided electrocautery ablation of tracheal liposarcoma was a safe and
      effective minimally invasive treatment for the dog of this report. The procedure
      was brief and appeared to be well tolerated, resulting in immediate improvement
      of clinical signs.

PMID- 29461159
TI  - Evaluation of tramadol for treatment of osteoarthritis in geriatric cats.
AB  - OBJECTIVE To evaluate tramadol for treatment of signs of pain and impaired
      mobility in geriatric cats with osteoarthritis. DESIGN Randomized controlled
      crossover trial. ANIMALS 24 client-owned geriatric (>= 10 years old) cats with
      osteoarthritis. PROCEDURES Otherwise healthy cats with owner-identified mobility
      impairment and clinical and radiographic evidence of osteoarthritis involving at
      least 1 appendicular joint were enrolled in the study. Cats were treated with
      tramadol orally at dosages of 0 (placebo), 1, 2, and 4 mg/kg (0, 0.45, 0.9, and
      1.8 mg/lb) twice a day for 5 days, with a 2-day (weekend) washout period between
      treatments. Mobility was assessed with a collar-mounted activity monitor system,
      and impairments in activity were assessed with a client-completed questionnaire.
      RESULTS 17 cats completed the study; 7 cats were withdrawn. There was a
      significant increase in activity with the 2-mg/kg dosage of tramadol, compared
      with activity when cats received the placebo. Significantly more owners (11/18)
      considered their cats to have improved with the 2-mg/kg treatment, compared with
      all other dosages (6/19 to 8/21). Most owners (17/20 [85%]) considered their
      cat's global quality of life to have improved during the study. Adverse events,
      predominantly euphoria, dysphoria, sedation, decreased appetite, and diarrhea,
      were significantly more frequent with the 4-mg/kg (8/19) and 2-mg/kg (6/18)
      treatments but not with the 1-mg/kg (2/21) treatment, compared with frequency of
      adverse events with the placebo (0/21). CONCLUSIONS AND CLINICAL RELEVANCE
      Results suggested a beneficial effect of twice-daily oral administration of
      tramadol at a dosage of 2 mg/kg in geriatric cats with osteoarthritis. Adverse
      events were dose dependent, and caution should be exercised in cats that have
      concurrent disease or are receiving other drugs that may produce adverse
      gastrointestinal effects.

PMID- 29461161
TI  - Helping students like Eliana and Aaron: advocating for a brighter financial
      future.

PMID- 29461160
TI  - Veterinarians' experiences with near misses and adverse events.
AB  - OBJECTIVE To assess the prevalence of medical errors (specifically, near misses
      [NMs] and adverse events [AEs]) and their personal and professional impact on
      veterinarians. DESIGN Cross-sectional study. SAMPLE Members of the Veterinary
      Information Network (n = 46,481). PROCEDURES An electronic survey regarding
      veterinarians' experiences with NMs and AEs was distributed via email to an
      online veterinary community between September 24 and October 21, 2015. Responses
      were summarized and compared between genders by means of the chi2 test. RESULTS
      606 veterinarians completed the survey (1.3% response rate). Overall, 447 (73.8%)
      respondents reported involvement in >= 1 NM (n = 389 [64.2%]) or AE (179
      [29.5%]). The NMs had a short-term (<= 1 week) adverse impact on professional
      life for 68.0% (261/384) of respondents and longer-term negative impact for 36.4%
      (140/385). The impact on respondents' personal lives was similar (63.6% [245/385]
      and 33.5% [129/385], respectively). For AEs, these numbers were 84.1% (148/176),
      56.2% (99/177), 77.8% (137/176), and 50.6% (89/175), respectively. Both NMs and
      AEs were more likely to negatively impact female veterinarians than male
      veterinarians. CONCLUSIONS AND CLINICAL RELEVANCE These findings suggested that
      many veterinarians experience emotional distress after a medical error. Support
      should be provided to mitigate this adverse impact on the wellbeing of
      veterinarians and, potentially, their future patients.

PMID- 29461162
TI  - An online survey of small animal veterinarians regarding current fluid therapy
      practices in dogs and cats.
AB  - OBJECTIVE To determine common fluid therapy practices of small animal
      practitioners and identify fluid therapy-related knowledge gaps that may benefit
      from improved educational efforts, targeted research, or both. DESIGN Online
      survey. SAMPLE 1,496 small animal veterinarians PROCEDURES An online survey was
      provided to members of the Veterinary Information Network between December 23,
      2013, and January 30, 2014. The survey consisted of 24 questions investigating
      the administration of crystalloid and synthetic colloid solutions, but not blood
      products, and focused primarily on the choice of fluid type, frequency of
      administration, type of patient treated with fluids, treatment with fluids
      subcutaneously versus IV, and potassium supplementation of fluids. Only responses
      from practicing small animal veterinarians were included. Not all respondents
      answered every question, and some questions allowed > 1 answer. RESULTS Balanced
      crystalloid solutions were the most common fluid type in all clinical scenarios
      described. The most common maintenance IV fluid rate reported by respondents
      (762/1,333 [57%]) was 60 mL/kg/d (27 mL/lb/d); calculation of fluid
      administration rate by means of body surface area was infrequent. Challenges of
      fluid therapy included determining the appropriate rate (572/1,496 [38%]) and
      fluid type (497/1,496 [33%]) and determining the need for potassium
      supplementation (229/1,496 [15%]). CONCLUSIONS AND CLINICAL RELEVANCE Small
      animal veterinarians tended to favor isotonic balanced crystalloid solutions for
      IV fluid therapy, compared with other common choices such as isotonic saline
      (0.9% NaCl) solution. Despite its ubiquity, respondents found many aspects of
      fluid therapy to be challenging, suggesting the need for easy to use, evidence
      based guidelines.

PMID- 29461163
TI  - Pathology in Practice.

PMID- 29461165
TI  - What Is Your Diagnosis?

PMID- 29461166
TI  - Radiographic outcome of root canal treatment of canine teeth in cats: 32 cases
      (1998-2016).
AB  - OBJECTIVE To describe the radiographic outcome of root canal treatment (RCT) of
      canine teeth of cats. DESIGN Retrospective case series. ANIMALS 32 cats with 37
      canine teeth with complicated crown fractures that underwent RCT. PROCEDURES
      Medical record databases of 5 referral veterinary hospitals were searched to
      identify cats that underwent RCT between 1998 and 2016. Only cats that had at
      least 1 follow-up examination during which radiographs were obtained of the
      treated canine tooth or teeth were included in the study. Dental radiographs
      obtained before and immediately after RCT and during all follow-up examinations
      were reviewed. Treatment was considered successful if the periodontal ligament
      space was within reference limits and preoperative external inflammatory root
      resorption (EIRR), if present, had stabilized. Treatment was considered to have
      no evidence of failure if preoperative EIRR had stabilized and preexisting
      periapical lucency was stable or decreased in size but had not resolved.
      Treatment was considered to have failed if periapical lucency or EIRR developed
      subsequent to RCT or preexisting periapical lucency increased in size or
      preoperative EIRR progressed following RCT. RESULTS Follow-up time after RCT
      ranged from 3 to 72 months. The RCT was successful for 18 (49%) of the 37 treated
      teeth, had no evidence of failure for 12 (32%), and failed for 7 (19%).
      Preexisting EIRR and patient age >= 5 years significantly increased the rate of
      RCT failure. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that RCT was a
      viable treatment option to salvage endodontically diseased canine teeth in cats.

PMID- 29461168
TI  - Letters to the Editor.

PMID- 29461167
TI  - Incidence of hospital-acquired anemia in hospitalized dogs and cats.
AB  - OBJECTIVE To determine the incidence of hospital-acquired anemia among dogs and
      cats hospitalized at a private emergency and referral center and identify
      possible risk factors. DESIGN Prospective, observational study. ANIMALS 56
      patients (46 dogs and 10 cats). PROCEDURES Patients admitted from August 2014
      through March 2015 and hospitalized for >= 48 hours were eligible for inclusion.
      Hospital-acquired anemia was defined as a PCV within reference limits on
      admission with development of anemia during hospitalization. Packed cell volume
      was measured once every 24 hours, and IV fluid volumes and blood volumes removed
      by means of phlebotomy were recorded. RESULTS The incidence of hospital-acquired
      anemia for dogs and cats combined was 34% (19/56) by 24 hours, 43% (24/56) by 48
      hours, and 48% (27/56) by 72 hours. The incidence of hospital-acquired anemia was
      70% (7/10) in cats and 43% (20/46) in dogs. Patients that underwent surgery had
      an increased odds of developing hospital-acquired anemia, compared with patients
      that did not undergo surgery (OR, 9.79; 95% confidence interval, 1.92 to 50.0).
      Cumulative phlebotomy volumes > 3% of total estimated blood volume significantly
      increased the risk of developing hospital-acquired anemia. CONCLUSIONS AND
      CLINICAL RELEVANCE Cumulative phlebotomy volumes > 3% of total blood volume and
      undergoing surgery significantly increased the risk that dogs and cats would
      develop hospital-acquired anemia. Further investigation is warranted for early
      identification of small animal patients at risk for development of hospital
      acquired anemia and to inform effective treatment strategies.

PMID- 29461169
TI  - Environmental stewardship practices of veterinary professionals and educators
      related to use and disposal of pharmaceuticals and personal care products.
AB  - OBJECTIVE To document the environmental stewardship practices (decisions and
      actions regarding use and disposal) of pet and human pharmaceuticals and personal
      care products (PPCPs) among pet-owning veterinary-care professionals (practicing
      veterinarians, veterinary students, and veterinary technicians and trainees) and
      environmental educators. DESIGN Internet-based cross-sectional survey. SAMPLE 191
      pet owners (103 veterinary-care professionals and 88 environmental educators).
      PROCEDURES Study participants were recruited by means of a 2-part internet survey
      distributed to veterinary-care professional and environmental educator networks
      of individuals residing in Washington state, Oregon, and southern California.
      Survey questions addressed motivators for environmental stewardship practices
      (ie, decisions and actions regarding use and disposal of pet and human PPCPs).
      RESULTS Data were collected from 191 respondents; the response rate for
      individuals who self-selected to opt in was 78% (191/246). Of the 191
      respondents, 42 (22%) stored pet pharmaceuticals indefinitely. The most common
      disposal method was the garbage (88/191 [46%]). Veterinary-care professionals
      counseled clients infrequently regarding environmental stewardship practices for
      PPCPs. Fifty-five percent (105/191) of all respondents preferred more
      environmentally friendly and clinically effective PPCPs. CONCLUSIONS AND CLINICAL
      RELEVANCE Results of the present survey emphasized the urgent need for improved
      educational resources to minimize environmental contamination from improper
      disposal of PPCPs. Environmental and economic motivations among pet owners in the
      veterinary-care and education professions indicate further opportunities for
      outreach and institutional support.

PMID- 29461170
TI  - In This Issue * March 1, 2018.

PMID- 29461171
TI  - New model of proliferative vitreoretinopathy in rabbit for drug delivery and
      pharmacodynamic studies.
AB  - Blinding retinal diseases become more epidemic as the population ages. These
      diseases, such as diabetic retinopathy and macular edema, are of chronic nature
      and require protracted drug presence at the disease site. A sustained
      intravitreal porous silicon delivery system with dexamethasone (pSiO2-COO-DEX)
      was evaluated in a new rabbit model of proliferative vitreoretinopathy (PVR) in a
      real treatment design. In contrast to the pretreatment design model, pSiO2-COO
      DEX was intravitreally injected into the eyes with active inflammation.
      Subretinal injection of vascular endothelial growth factor (VEGF) and Matrigel
      induced a late-onset vitreoretinal inflammation that gradually developed into
      PVR. This method mimics the human disease better than PVR induced by either
      intravitreal cell injection or trauma. The pSiO2-COO-DEX intervened eyes had
      minimal PVR, while balanced saline solution or free dexamethasone intervened eyes
      had significantly more PVR formation. In addition, adding VEGF to the Matrigel
      for subretinal injection induced greater inflammation and retinal
      neovascularization in comparison to only Matrigel injected under the medullary
      ray. Clinical and pathological examinations, including fundus fluorescein
      angiography and optical coherence tomography, confirmed these changes. In the
      current study, neither subretinal injection of Matrigel or subretinal injection
      of VEGF and Matrigel induced choroidal neovascularization. However, the current
      PVR model demonstrates a chronic course with moderate severity, which may be
      useful for drug screening studies.

PMID- 29461174
TI  - Faces, people and the brain: The 45th Sir Frederic Bartlett Lecture.
AB  - The fact that the face is a source of diverse social signals allows us to use
      face and person perception as a model system for asking important psychological
      questions about how our brains are organised. A key issue concerns whether we
      rely primarily on some form of generic representation of the common physical
      source of these social signals (the face) to interpret them, or instead create
      multiple representations by assigning different aspects of the task to different
      specialist components. Variants of the specialist components hypothesis have
      formed the dominant theoretical perspective on face perception for more than
      three decades, but despite this dominance of formally and informally expressed
      theories, the underlying principles and extent of any division of labour remain
      uncertain. Here, I discuss three important sources of constraint: first, the
      evolved structure of the brain; second, the need to optimise responses to
      different everyday tasks; and third, the statistical structure of faces in the
      perceiver's environment. I show how these constraints interact to determine the
      underlying functional organisation of face and person perception.

PMID- 29461172
TI  - Radiomics Based on Adapted Diffusion Kurtosis Imaging Helps to Clarify Most
      Mammographic Findings Suspicious for Cancer.
AB  - Purpose To evaluate a radiomics model of Breast Imaging Reporting and Data System
      (BI-RADS) 4 and 5 breast lesions extracted from breast-tissue-optimized kurtosis
      magnetic resonance (MR) imaging for lesion characterization by using a
      sensitivity threshold similar to that of biopsy. Materials and Methods This
      institutional study included 222 women at two independent study sites (site 1:
      training set of 95 patients; mean age +/- standard deviation, 58.6 years +/- 6.6;
      61 malignant and 34 benign lesions; site 2: independent test set of 127 patients;
      mean age, 58.2 years +/- 6.8; 61 malignant and 66 benign lesions). All women
      presented with a finding suspicious for cancer at x-ray mammography (BI-RADS 4 or
      5) and an indication for biopsy. Before biopsy, diffusion-weighted MR imaging (b
      values, 0-1500 sec/mm2) was performed by using 1.5-T imagers from different MR
      imaging vendors. Lesions were segmented and voxel-based kurtosis fitting adapted
      to account for fat signal contamination was performed. A radiomics feature model
      was developed by using a random forest regressor. The fixed model was tested on
      an independent test set. Conventional interpretations of MR imaging were also
      assessed for comparison. Results The radiomics feature model reduced false
      positive results from 66 to 20 (specificity 70.0% [46 of 66]) at the predefined
      sensitivity of greater than 98.0% [60 of 61] in the independent test set, with BI
      RADS 4a and 4b lesions benefiting from the analysis (specificity 74.0%, [37 of
      50]; 60.0% [nine of 15]) and BI-RADS 5 lesions showing no added benefit. The
      model significantly improved specificity compared with the median apparent
      diffusion coefficient (P < .001) and apparent kurtosis coefficient (P = .02)
      alone. Conventional reading of dynamic contrast material-enhanced MR imaging
      provided sensitivity of 91.8% (56 of 61) and a specificity of 74.2% (49 of 66).
      Accounting for fat signal intensity during fitting significantly improved the
      area under the curve of the model (P = .001). Conclusion A radiomics model based
      on kurtosis diffusion-weighted imaging performed by using MR imaging machines
      from different vendors allowed for reliable differentiation between malignant and
      benign breast lesions in both a training and an independent test data set. (c)
      RSNA, 2018 Online supplemental material is available for this article.

PMID- 29461175
TI  - Editorial: Epigenetics in Oromaxillafacial Development and Disease.

PMID- 29461176
TI  - Editorial: Targeting Cerebral Vascular Injury for Intervention.

PMID- 29461177
TI  - Editorial: Challenges in HIV Epidemiology, Prevention and Treatment.

PMID- 29461178
TI  - Correlates and Predictors of New Mothers' Responses to Postpartum Thoughts of
      Accidental and Intentional Harm and Obsessive Compulsive Symptoms.
AB  - BACKGROUND: Unwanted, intrusive thoughts of infant-related harm are a normal,
      albeit distressing experience for most new mothers. The occurrence of these
      thoughts can represent a risk factor for the development of obsessive compulsive
      disorder (OCD). As the early postpartum period represents a time of increased
      risk for OCD development, the transition to parenthood provides a unique
      opportunity to better understand OCD development. AIMS: The purpose of this study
      was to assess components of cognitive behavioural conceptualizations of
      postpartum OCD in relation to new mothers' thoughts of infant-related harm.
      METHOD: English-speaking pregnant women (n = 100) participated. Questionnaires
      were completed at approximately 36 weeks of gestation, and at 4 and 12 weeks
      postpartum. An interview to assess postpartum harm thoughts was administered at 4
      and 12 weeks postpartum. Questionnaires assessed OC symptoms, OC-related beliefs,
      fatigue, sleep difficulties and negative mood. RESULTS: Prenatal OC-related
      beliefs predicted postpartum OC symptoms, as well as harm thought characteristics
      and behavioural responses to harm thoughts. The severity of behavioural responses
      to early postpartum harm thoughts did not predict later postpartum OC symptoms,
      but did predict frequency and time occupation of accidental harm thoughts, and
      interference in parenting by intentional harm thoughts. Strong relationships
      between OC symptoms and harm thought characteristics, and concurrent sleep
      difficulties, negative mood and fatigue were also found. CONCLUSIONS: Findings
      provide support for cognitive behavioural conceptualizations of postpartum OCD
      and emphasize the importance of maternal sleep, fatigue and negative mood in the
      relationship between OC-related beliefs and maternal cognitive and behavioural
      responses to postpartum harm thoughts.

PMID- 29461179
TI  - Oleiharenicola alkalitolerans gen. nov., sp. nov., a new member of the phylum
      Verrucomicrobia isolated from an oilsands tailings pond.
AB  - A novel member of the phylum Verrucomicrobia was isolated from an oilsands
      tailings pond in Alberta, Canada. Cells of isolate NVTT are Gram-negative,
      strictly aerobic, non-pigmented, non-motile cocci to diplococci 0.5-1.0 um in
      diameter. The bacterium is neutrophilic (optimum pH 6.0-8.0) but alkalitolerant,
      capable of growth between pH 5.5 and 11.0. The temperature range for growth is 15
      40  degrees C (optimum 25-37  degrees C). Carbon and energy sources include
      sugars and organic acids. Nitrogen sources include nitrate, urea, l-glycine, l
      alanine, l-proline and l-serine. Does not fix atmospheric nitrogen. Does not
      require NaCl and is inhibited at NaCl concentrations above 3.0 % (w/v). The DNA
      G+C content of strain NVTT, based on a draft genome sequence, is 66.1 mol%. MK-6
      and MK-7 are the major respiratory quinones. Major cellular fatty acids are
      anteiso-C15 : 0 and iso-C15 : 0. Phylogenetic analysis of 16S rRNA gene sequences
      revealed that the strain belongs to the family Opitutaceae of the phylum
      Verrucomicrobia. The most closely related validated species is Opitutus terrae
      (93.7 % 16S rRNA gene sequence identity to its type strain PB90-1T). Based on
      genotypic, phenotypic and chemotaxonomic characteristics, it was concluded that
      this strain represents a novel genus and species, for which the name
      Oleiharenicola alkalitolerans gen. nov., sp. nov. is proposed. The type strain of
      this novel species is NVTT (=ATCC BAA-2697T;=DSM 29249T).

PMID- 29461180
TI  - Pedobacter mongoliensis sp. nov., isolated from grassland soil.
AB  - A Gram-stain-negative, rod-shaped, motile by gliding and strictly aerobic
      bacterial strain, named 1-32T, was isolated from soil of the Ordos grassland in
      Inner Mongolia, PR China. Strain 1-32T showed highest 16S rRNA gene sequence
      similarities to Pedobacter luteus N7d-4T (95.4 %), Pedobacter oryzae DSM 19973T
      (95.3 %), 'Pedobacter xinjiangensis' 12157T (95.2 %) and Pedobacter
      tournemirensis TF5-37.2-LB10T (95.1 %). Phylogenetic analyses clustered strain 1
      32T with 'P. xinjiangensis' 12157T and P. tournemirensis TF5-37.2-LB10T. The DNA
      G+C content was 43.4 mol%. Menaquinone 7 was the main respiratory quinone. The
      predominant fatty acids (>5 %) were iso-C15 : 0, summed feature 3 (C16 : 1omega6c
      and/or C16 : 1omega7c), iso-C17 : 0 3-OH, iso-C15 : 0 3-OH and C16 : 1omega5c.
      The polar lipids of strain 1-32T comprised phosphatidylethanolamine, two
      unidentified polar lipids, one unidentified glycolipid and two unidentified
      phospholipids. Strain 1-32T could be distinguished from the other members of the
      genus Pedobacter based on its phylogenetic distance and physiological and
      biochemical characteristics such as being negative for the assimilation of
      rhamnose and the activity of alpha-glucosidase. Therefore, strain 1-32T
      represents a novel species of the genus Pedobacter, for which the name Pedobacter
      mongoliensis sp. nov. is proposed. The type strain is 1-32T (=KCTC 52859T=CCTCC
      AB 2017084T).

PMID- 29461181
TI  - Paraburkholderia aromaticivorans sp. nov., an aromatic hydrocarbon-degrading
      bacterium, isolated from gasoline-contaminated soil.
AB  - A Gram-stain-negative, facultatively aerobic, aromatic hydrocarbon-degrading
      bacterium, designated strain BN5T, was isolated from gasoline-contaminated soil.
      Cells were motile and slightly curved rods with a single flagellum showing
      catalase and oxidase activities. Growth was observed at 20-37  degrees C
      (optimum, 25-30  degrees C), pH 3-7 (optimum, pH 5-6) and 0-2 % NaCl (optimum, 0
      %). Ubiquinone-8 was the predominant respiratory quinone. The major fatty acids
      were C16 : 0, cyclo-C19 : 0omega8c and summed feature 8 (comprising C18 :
      1omega7c and/or C18 : 1omega6c). Diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine, an unidentified phosphoamino lipid, three unidentified
      amino lipids and eight unidentified lipids were the identified polar lipids. The
      DNA G+C content was 62.93 mol%. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed that strain BN5T formed a phylogenic lineage with members of
      the genus Paraburkholderia and showed the highest 16S rRNA gene sequence
      similarities to Paraburkholderia phytofirmans PsJNT (99.4 %), Paraburkholderia
      dipogonis DL7T (98.8 %) and Paraburkholderia insulsa PNG-AprilT (98.8 %). The
      average nucleotide identity and in silico DNA-DNA hybridization (DDH) values
      between strain BN5T and P. phytofirmans PsJNT were 88.5 and 36.5 %, respectively.
      The DDH values for strain BN5T with P. dipogonis LMG 28415T and P. insulsa DSM
      28142T were 41.0+/-4.9 % (reciprocal, 33.0+/-4.3 %) and 47.1+/-6.6 % (reciprocal,
      51.7+/-5.4 %), respectively. Based on its physiological, chemotaxonomic and
      phylogenetic features, we conclude that strain BN5T is a novel species of the
      genus Paraburkholderia, for which the name Paraburkholderia aromaticivorans sp.
      nov. is proposed. The type strain is BN5T (=KACC 19419T=JCM 32303T).

PMID- 29461182
TI  - Molecular characterization and antifungal susceptibility testing of Cryptococcus
      neoformans sensu stricto from southern Brazil.
AB  - PURPOSE: Cryptococcosis is acquired from the environment by the inhalation of
      Cryptococcus cells and may establish from an asymptomatic latent infection into
      pneumonia or meningoencephalitis. The genetic diversity of a Cryptococcus
      neoformans species complex has been investigated by several molecular tools, such
      as multi-locus sequence typing, amplified fragment length polymorphism (AFLP),
      restriction fragment length polymorphism and microsatellite analysis. This study
      aimed to investigate the genotype distributions and antifungal susceptibility
      profiles of C. neoformans sensu lato isolates from southern Brazil. METHODOLOGY:
      We studied 219 C. neoformans sensu lato isolates with mating- and serotyping,
      AFLP fingerprinting, microsatellite typing and antifungal susceptibility
      testing.Results/Key findings. Among the isolates, 136 (69 %) were from HIV
      positive patients. Only C. neoformans mating-type alpha and serotype A were
      observed. AFLP fingerprinting analysis divided the isolates into AFLP1/VNI
      (n=172; 78.5 %), AFLP1A/VNII (n=19; 8.7 %), AFLP1B/VNII (n=4; 1.8 %) and a new
      AFLP pattern AFLP1C (n=23; 10.5 %). All isolates were susceptible to tested
      antifungals and no correlation between antifungal susceptibility and genotypes
      was observed. Through microsatellite analysis, most isolates clustered in a major
      microsatellite complex and Simpson's diversity index of this population was
      D=0.9856. CONCLUSION: The majority of C. neoformans sensu stricto infections
      occurred in HIV-positive patients. C. neoformans AFLP1/VNI was the most frequent
      genotype and all antifungal drugs had high in vitro activity against this
      species. Microsatellite analyses showed a high genetic diversity within the
      regional C. neoformans sensu stricto population, and correlation between
      environmental and clinical isolates, as well as a temporal and geographic
      relationship.

PMID- 29461183
TI  - Roseovarius nitratireducens sp. nov., a halotolerant bacterium isolated from a
      saline lake.
AB  - A Gram-stain-negative, aerobic, non-motile and ovoid- to rod-shaped bacterial
      strain, designated TFZT, was isolated from a water sample of a saline lake in
      Xinjiang, China and subjected to polyphasic taxonomic investigation. Strain TFZT
      grew at 4-42  degrees C and pH 6.5-10.0 (optimum, 30  degrees C and pH 7.0) and
      with 0.5-18.0 % (w/v) NaCl (optimum, 1.5 %). According to phylogenetic analysis
      based on 16S rRNA gene sequences, strain TFZT was assigned to the genus
      Roseovarius with highest 16S rRNA gene sequence similarity of 97.5 % to
      Roseovarius tolerans EL-172T, followed by Roseovarius azorensis SSW084T (96.6 %)
      and Roseovarius mucosus DSM 17069T (95.5 %). Digital DNA-DNA hybridization (DDH)
      and average nucleotide identity (ANI) were determined to evaluate the genomic
      relationship between strain TFZT and R. tolerans EL-172T. Digital DDH estimation
      (22.80+/-2.35 %) as well as ANI (80.1 %) proved the dissimilarity of strain TFZT.
      Chemotaxonomic analysis showed that strain TFZT contained ubiquinone-10 as the
      predominant respiratory quinone and possessed summed feature 8 (comprising C18 :
      1omega7c and/or omega6c) and C16 : 0 as the predominant form of fatty acid. The
      polar lipids of strain TFZT consisted of phosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylcholine and five unidentified lipids. The
      DNA G+C content was 65.4 mol% (by genome sequencing). Based on the polyphasic
      taxonomic characterization, strain TFZT is considered to represent a novel
      species of the genus Roseovarius, for which the name Roseovariusnitratireducens
      sp. nov. is proposed (type strain TFZT=MCCC 1K03339T=KCTC 52967T).

PMID- 29461184
TI  - Cryobacterium aureum sp. nov., a psychrophilic bacterium isolated from glacier
      ice collected from the ice tongue surface.
AB  - A psychrophilic, Gram-stain-positive, rod-shaped bacterium, designated strain
      Hh31T, was isolated from Xinjiang No. 1 Glacier in China. Strain Hh31T was
      catalase-positive, oxidase-negative and able to grow at between 0-18  degrees C.
      Phylogenetic analysis based on 16S rRNA gene sequences showed that strain Hh31T
      belonged to the genus Cryobacterium and was most closely related to the type
      strains of Cryobacterium levicorallinum, Cryobacterium luteum and Cryobacterium
      flavum. DNA-DNA hybridization, calculation of average nucleotide identity and
      digital DNA-DNA hybridization revealed that strain Hh31T was distinct from its
      closest phylogenetic neighbours. The major cellular fatty acids of strain Hh31T
      were anteiso-C15 : 0, anteiso-C15 : 1, iso-C15:0, iso-C16 : 0 and anteiso-C17 :
      0. The predominant menaquinones of strain Hh31T were MK-9 and MK-10. The polar
      lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, one
      unidentified phospholipid, one unidentified glycolipid and another unidentified
      lipid. Physiological tests such as carbon source utilization, showed phenotypic
      differentiation of strain Hh31T from the closest related phylogenetic neighbours.
      Based on a polyphasic approach, a novel species, Cryobacterium aureum sp. nov.,
      is proposed, with Hh31T (=NBRC 107882T=CGMCC 1.11213T) as the type strain.

PMID- 29461185
TI  - 1,4-Naphthoquinone derivatives potently suppress Candida albicans growth, inhibit
      formation of hyphae and show no toxicity toward zebrafish embryos.
AB  - PURPOSE: In this study, we applied various assays to find new activities of 1,4
      naphthoquinone derivatives for potential anti-Candida albicans applications.
      METHODOLOGY: These assays determined (a) the antimicrobial effect on growth/cell
      multiplication in fungal cultures, (b) the effect on formation of hyphae and
      biofilm, (c) the influence on cell membrane integrity, (d) the effect on cell
      morphology using atomic force microscopy, and (e) toxicity against zebrafish
      embryos. We have demonstrated the activity of these compounds against different
      Candida species and clinical isolates of C. albicans. KEY FINDINGS: 1,4
      Naphthoquinones significantly affected fungal strains at 8-250 mg l-1 of MIC.
      Interestingly, at concentrations below MICs, the chemicals showed effectiveness
      in inhibition of hyphal formation and cell aggregation in Candida. Of note,
      atomic force microscopy (AFM) analysis revealed an influence of the compounds on
      cell morphological properties. However, at low concentrations (0.8-31.2 mg l-1),
      it did not exert any evident toxic effects on zebrafish embryos. CONCLUSIONS: Our
      research has evidenced the effectiveness of 1,4-naphthoquinones as potential anti
      Candida agents.

PMID- 29461186
TI  - Saturnispora kantuleensis f.a., sp. nov., a novel yeast species isolated from
      peat in a tropical peat swamp forest in Thailand.
AB  - Two strains (DMKU-PPS4-5T and DMKU-EPS3-4) representing a single novel anamorphic
      yeast species were isolated from two peat samples collected in Kan Tulee peat
      swamp forest, Surat Thani Province, Thailand. The strains differed by two
      nucleotide substitutions in the sequences of the D1/D2 region of the large
      subunit (LSU) rRNA gene and only one nucleotide substitution in the internal
      transcribed spacer (ITS) region. Phylogenetic analysis based on the D1/D2 regions
      showed that the two strains represented a single species in the genus
      Saturnispora and were clearly distinct from other related species. Saturnispora
      sekii was the most closely related species, but with 1.7-2.1 % nucleotide
      substitutions in the D1/D2 region of the LSU rRNA gene, and 3.1-3.3 % nucleotide
      substitutions in the ITS region. They therefore represent a novel species of the
      genus Saturnispora, although the formation of ascospores was not observed. The
      name Saturnispora kantuleensis f.a., sp. nov. is proposed. The type strain is
      DMKU-PPS4-5T (=CBS 15217T=TBRC 7762T).

PMID- 29461187
TI  - Detection of Coxiella burnetii in heart valve sections by fluorescence in situ
      hybridization.
AB  - PURPOSE: Infective endocarditis is a severe and potentially fatal disease. Nearly
      a third of all cases remain culture-negative, making a targeted and effective
      antibiotic therapy of patients challenging. In the past years, fluorescence in
      situ hybridization (FISH) has proven its value for the diagnosis of infective
      endocarditis, particularly when it is caused by fastidious bacteria. To increase
      the number of infective endocarditis causing agents, which can be identified by
      FISH, we designed and optimized a FISH-probe for the specific detection of
      Coxiella burnetii in heart valve tissue. METHODOLOGY: Even with specific probes
      the detection and identification of bacteria can be complicated by the high
      autofluorescence due to calcification of the analysed tissue. To overcome this
      problem, we developed a protocol to detect C. burnetii by hybridizing, stripping
      and reprobing the identical section with different species-specific probes
      repeatedly.Results/Key findings. The newly designed specific FISH probe and the
      developed protocol exemplarily allowed us to unequivocally identify C. burnetii
      in tissue sections of a patient with infective endocarditis. CONCLUSION: This
      method provides an add-on to existing protocols for the unambiguous diagnosis of
      bacteria directly within tissues or other difficult tissue samples in cases with
      small sample size and limited sections.

PMID- 29461188
TI  - Evolution of Health Literacy Research in Orthopaedics and Other Medical
      Specialties.

PMID- 29461189
TI  - Evaluating Nonoperative Treatments for Adhesive Capsulitis.
AB  - Patients commonly present with shoulder complaints to the primary care and
      orthopaedic setting. The differential includes rotator cuff tears, subacromial
      impingement, osteoarthritis, and adhesive capsulitis, also known as frozen
      shoulder. Despite the prevalence of adhesive capsulitis, it is commonly
      misdiagnosed and management remains unclear. This article reviews the
      presentation of adhesive capsulitis, presents an overview of the pathophysiology
      of this poorly understood disease, and evaluates nonoperative treatment options
      for adhesive capsulitis. (Journal of Surgical Orthopaedic Advances 26(4):193-199,
      2017).

PMID- 29461190
TI  - Outcomes of Below-the-Knee Amputations for Chronic Lower Extremity Pain.
AB  - The study evaluated the physical,mental, and functional outcomes following below
      the-knee amputation (BKA) for management of chronic, debilitating lower extremity
      pain. The hypothesis was that patients who undergo a BKA to alleviate chronic
      pain achieve a greater level of function, experience decreased pain, and benefit
      from improved health-related quality of life. Patients who received a BKA
      attended an orthopaedic clinic and completed questionnaires examining their
      overall health, functional status, mental health, and pain. Thirty-seven patients
      were identified as eligible for study participation; 15 agreed to participate.
      Although most participants continued to experience pain in their residual limb
      after BKA, they reported their pain decreased to a manageable level. Participants
      experienced a statistically significant improvement in their perceived physical
      health. The authors believe a BKA for chronic pain is a reasonable treatment
      option for patients who continue to experience lower extremity pain after failed
      medical and surgical management of chronic pain. (Journal of Surgical Orthopaedic
      Advances 26(4):200-205, 2017).

PMID- 29461191
TI  - Predictability of Lower Extremity Peripheral Nervous Anatomy.
AB  - Lower extremity nervous anatomy is highly variable. This study sought to
      determine relationships of lower extremity peripheral nerves to anatomic
      landmarks. Sixteen well-preserved lower extremities were dissected. The distance
      from each nerve point of interest to relevant landmarks was measured in
      standardized fashion. The sciatic nerve divided on average 26.0% +/- 5% of the
      distance from the superior aspect of the fibula to the greater trochanter
      proximal to the knee joint line [Pearson correlation coefficient (PCC) D 0.764].
      The superficial peroneal nerve pierced the crural fascia at an average of 28.0%
      +/- 6% of the fibular length proximal to the lateral malleolus (PCC D 0.718). The
      deep peroneal nerve emerged between the tibialis anterior and extensor hallucis
      longus on average 2.7% +/- 0.4% of the fibular length proximal to the tibiotalar
      joint line (PCC D 0.530). While there was substantial variability in the course
      of lower extremity peripheral nerves, the study found strong correlation with
      femur and fibula length within each specimen. (Journal of Surgical Orthopaedic
      Advances 26(4):206-210, 2017).

PMID- 29461192
TI  - Return of Quadriceps Strength After Primary Total Knee Arthroplasty With Single
      Radius Knee System: Five-Year Follow-up.
AB  - Preoperative quadriceps muscle strength (isometric peak torque) was expectedly
      lower on the total knee arthroplasty side in comparison with the unaffected
      contralateral side and it was further reduced after surgery. This reduction
      continued for up to 6 months postoperatively. After 6 months, muscle strengths
      exceeded preoperative values and continued to increase for the following 2 years.
      From 2 to 5 years postoperatively, there was a tendency for decline; however, the
      quadriceps muscle strength still exceeded preoperative values. On the
      nonoperative side, the increase in muscle strength was detected 1 year after
      surgery and it was still noticeable at 5 years. Contralateral side improvement
      can be explained by the increased mobility of the patients. Knee Society Scores
      and function scores were significantly increased at 3 months after surgery and
      were significantly greater than preoperative values 5 years after surgery. SF-12
      (physical score) exceeded preoperative values at 3 months and this increase was
      observed continuously over the 5-year follow-up. (Journal of Surgical Orthopaedic
      Advances 26(4):211-215, 2017).

PMID- 29461193
TI  - Blood Transfusion After Primary Total Hip Arthroplasty: National Trends and
      Perioperative Outcomes.
AB  - The purpose of this study was to quantify the changes in transfusion rates, both
      allogeneic blood transfusion (ALBT) and autogenic blood transfusion (ATBT) on a
      national scale, and determine patient factors associated with transfusions. The
      National Hospital Discharge Survey was evaluated between 2001 and 2010 for
      primary total hip arthroplasty (THA) patients and categorized on the basis of
      transfusion necessity, type, and comorbidity burden. A logistic regression
      comparison of ALBT, ATBT, and nontransfused patients was performed with respect
      to patient demographics and in-hospital complications. The proportion of patients
      requiring any transfusion decreased from an average rate of 22.8% between 2001
      and 2005 to 21.2% between 2006 and 2010 (p = .01). ATBT rates decreased (r = 
      .99) from 11.0% in 2001 to 2.8% in 2010. ALBT rates increased (r = .66) from 14%
      in 2001 to 16.6% in 2010. The number of patients requiring a blood transfusion
      after THA decreased in the United States with a trend shifting from ATBT to ALBT.
      (Journal of Surgical Orthopaedic Advances 26(4):216-222, 2017).

PMID- 29461194
TI  - Smartphone-Based Goniometry Accuracy in Clinical Scenarios.
AB  - This study compared two popular iPhone-based goniometer applications to the gold
      standard universal goniometer for the measurement of the hip and knee joints in
      scenarios mimicking the normal pace of an orthopaedic clinical practice.Three
      physicians measured hip and knee joint angles 35 times with one of three
      goniometers: universal 12-inch goniometer, DrGoniometer (iPhone-5 based), and
      SimpleGoniometer (iPhone-5 based). Data wwere analyzed using Pearson correlation
      coefficient calculations. Average knee angles measured with the universal
      goniometer, DrGoniometer, and SimpleGoniometer measured 83.46 degrees , 85.23
      degrees , and 80.39 degrees , respectively. The smartphone-based goniometers had
      moderate agreement with the universal goniometer in the knee (r > .322). Average
      hip angles measured with the universal goniometer, DrGoniometer, and
      SimpleGoniometer measured 62.34 degrees , 60.87 degrees , and 59.34 degrees ,
      respectively. The smartphone-based goniometers had moderate agreement with the
      universal goniometer in the hip (r > .168). Smartphone-based goniometers gave
      accurate, with weak to moderate correlation, measurements for the knee and hip.
      (Journal of Surgical Orthopaedic Advances 26(4):223-226, 2017).

PMID- 29461195
TI  - Predictors of Carpal Tunnel Release After Open Distal Radius Fracture.
AB  - The purpose of this investigation was to determine the incidence and identify the
      predictors of carpal tunnel release (CTR) after open fractures of the distal
      radius (DRF). Patients with clinical symptoms of persistent median nerve
      neuropathy that required CTR were analyzed for risk factors. One hundred thirty
      nine open DRFs (107 grade I, 23 grade II, 9 grade III) met the inclusion
      criteria. The incidence of CTR was 13.7% in all open DRFs (19 out of 139).
      Multivariable logistic regression analysis identified four predictors: male sex
      [odds ratio (OR) = 8.8, p = .001], type III Gustilo and Anderson grade (OR = 6.2,
      p = .04), OTA fracture type C (OR = 3.8, p = .03), and the application of
      external fixation (OR = 14.0, p D .02). The probability of CTR, determined by
      preoperative variables, was 80% with three factors present and 2% with no risk
      factors. High-risk patients may be identified who may benefit from closer
      perioperative surveillance and possibly carpal tunnel release. (Journal of
      Surgical Orthopaedic Advances 26(4):227-232, 2017).

PMID- 29461196
TI  - Intramedullary Bone Graft Harvest Using Reamer-Irrigator-Aspirator System: A Case
      Series.
AB  - Autogenous iliac crest bone grating has been the gold standard. Recently,
      intramedullary bone graft harvest using a reamer-irrigator-aspirator (RIA) had
      been gaining more interest among orthopedic surgeons. Twenty-four RIA bone graft
      harvesting procedures in 23 consecutive patients with nonunions were included.
      The mean age was 37.8 years. Rates of perioperative complications, secondary
      surgical procedures, and union were assessed for all patients. At mean 10.1
      months follow-up, three donor site complications occurred (12.5%), including two
      fractures (8.3%). Eighteen patients (78%) progressed to radiographic union, three
      (13%) were lost for follow-up, and two (9%) failed to achieve union. Mean reamer
      size was 13.7 mm (mode, 14.0 mm), producing an average volume of 39.4 mL (range,
      15-90 mL) bone graft. While RIA bone grafting results in predictably high rates
      of union, patients should be counseled extensively about fracture risk. Tibial
      RIA may be less optimal as a primary source of bone grafting. (Journal of
      Surgical Orthopaedic Advances 26(4):233-238, 2017).

PMID- 29461197
TI  - Risk of Obtaining Routine Cultures During Presumed Aseptic Orthopaedic
      Procedures.
AB  - Treating patients with antibiotics that are selected based on routine cultures
      obtained from presumed aseptic orthopaedic procedures may lead to an increased
      risk of antibiotic-related complications without reducing the rate of late deep
      infection. Routine cultures obtained from 60 of 169 procedures resulted in 23
      (38.3%) positive and 37 (61.7%) negative results. Twenty-two patients (13.5%)
      developed late infections. Seven of 14 patients with positive cultures, who were
      treated with antibiotics, developed a late infection, while two of nine patients
      with routine cultures, who received no antibiotic treatment, developed a late
      infection. Six of 37 patients with negative cultures and seven of 109 patients
      with no cultures developed a late infection. In patients who developed late deep
      infection, the microorganism isolated on routine culture only corresponded to the
      microorganism causing late infection 55.5% of the time. Of all patients treated
      with antibiotics, seven (29%) experienced an antibiotic-related complication (p =
      .01). (Journal of Surgical Orthopaedic Advances 26(4):239-245, 2017).

PMID- 29461198
TI  - Radiation Exposure to the Orthopaedic Surgeon and Efficacy of a Novel Radiation
      Attenuation Product.
AB  - The purpose of this study was to examine the intraoperative radiation dosage to
      different body parts and to determine the effectiveness of a new lightweight
      radiation-attenuating fabric (XPF) versus lead, the current standard. For 51
      cases involving fluoroscopy, one attending orthopaedic surgeon wore a set of
      three dosimeters at various locations. Per each set of three, one dosimeter was
      shielded with a swatch of XPF, one was placed underneath the lead apron, and one
      was left exposed. The total dose of radiation was tabulated per body site and the
      percent attenuation was calculated for both XPF and lead. There was no
      statistically significant difference in the percent of radiation attenuation by
      lead and XPF (p = .47). The use of XPF produced 57.83% reduction in weight
      compared with lead when adjusting for total surface body area. XPF can be used
      for operating room personnel and patients, providing effective protection from
      radiation. (Journal of Surgical Orthopaedic Advances 26(4):246-249, 2017).

PMID- 29461199
TI  - Patient Satisfaction After Bilateral Thumb Carpometacarpal Osteoarthritis
      Surgery.
AB  - This study seeks to determine whether patients with bilateral thumb
      carpometacarpal osteoarthritis were sufficiently satisfied with their surgeries
      to choose to undergo surgery again. The null hypothesis is that patients are
      dissatisfied with the results of the first surgery. Out of 46 living patients
      meeting enrollment criteria, 41 were enrolled and evaluated using the
      Disabilities of the Arm, Shoulder and Hand (DASH) score and the Enneking
      musculoskeletal score. The average DASH score was 17.37. The average Enneking
      musculoskeletal score was 88.21. Of 41 patients, one expressed unwillingness to
      undergo the next procedure, three indicated that they would reluctantly do
      surgery again, and four were satisfied. The remaining 33 subjects were enthused
      with their functional result, expressing willingness to undergo the procedure
      again. At an average follow-up of 44.9 months, most patients are satisfied with
      bilateral thumb carpometacarpal surgery for osteoarthritis. Consent for the
      contralateral surgery implies that the outcome of the first surgery was
      sufficiently acceptable to seek surgery on the contralateral thumb. (Journal of
      Surgical Orthopaedic Advances 26(4):250-256, 2017).

PMID- 29461200
TI  - Implementation of a Service-Specific Template Integrating Objective Structured
      Clinical Examination and Accreditation Council for Graduate Medical Education
      Milestones: One Institution's Experience.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) orthopaedic
      milestones require detailed, frequent resident evaluations. This institution
      desired a cost-effective objective structured clinical examination (OSCE) to
      facilitate these evaluations. Data were collected as a prospective, uncontrolled
      observational study. The OSCE was completed by residents entering and exiting the
      foot and ankle rotation during postgraduate years 2 and 4. Physician assistants
      functioned as standardized patients. Statistical analyses were performed using
      paired and independent t tests. The OSCE was implemented using reliable, low-cost
      modalities and has facilitated milestones evaluations. Preliminary data show 4th
      year residents performed higher in prerotation global assessment with a
      standardized patient and written exam (p < .03). Second-year residents showed
      improvement in the written exam on rotation completion (p = .03). Using this
      methodology, institutions may establish similar cost-effective OSCEs as feasible
      evaluative solutions to satisfy milestone requirements. The authors believe this
      tool may be modified for any specialty. (Journal of Surgical Orthopaedic Advances
      26(4):257-261, 2017).

PMID- 29461201
TI  - Return to Duty Following a Tibial Tubercle Osteotomy.
AB  - Anterior knee pain is a common complaint among military members, with a negative
      impact on operational readiness. A tibial tubercle osteotomy is one treatment
      option for select etiologies of anterior knee pain and has been reported to
      result in high rates of return to activity. A retrospective review of active duty
      service members undergoing a tibial tubercle osteotomy at a single army medical
      center was performed. Thirteen active duty service members were identified as
      undergoing a tibial tubercle osteotomy. Nine patients remained on active duty at
      1 year following surgery. After 24 months, only four service members remained on
      active duty, while seven were medically retired. Seventy-five percent of patients
      who underwent concomitant cartilaginous procedure underwent a medical discharge.
      A small subset of active duty military personnel who underwent a tibial tubercle
      osteotomy was able to remain on active duty, but concomitant cartilaginous
      procedures did not appear to be compatible with retention on active duty because
      of the high physical demands placed on soldiers. (Journal of Surgical Orthopaedic
      Advances 26(4):262-265, 2017).

PMID- 29461202
TI  - Plantar Fibromatosis and Other Fibroblastic and Fibrohistiocytic Soft Tissue
      Tumors of the Foot.
AB  - Plantar fibromatosis, also known as Ledderhose's disease, is a benign
      fibroblastic disorder of plantar aponeurosis, more specifically the medial side
      of the foot arch. Magnetic resonance imaging (MRI) has an important role in the
      diagnosis, staging, and determining the deep extension found in advanced,
      aggressive forms of plantar fibromatosis, thereby guiding appropriate clinical
      and surgical management. This case report aims to provide radiologists and
      clinicians with simple guidelines for the differential diagnosis of the
      fibroblastic and fibrohistiocytic soft tissue tumors of the foot with the
      emphasis on the MRI findings. (Journal of Surgical Orthopaedic Advances 26(4):266
      270, 2017).

PMID- 29461203
TI  - Circulating CD34+ hematopoietic stem/progenitor cells paralleled with level of
      viremia in patients chronically infected with hepatitis B virus.
AB  - INTRODUCTION: Liver regeneration is a heterogeneous process involving
      proliferation of different cell types in response to injury. Bone marrow derived
      stem cells may be involved in this process, by making contribution to parenchymal
      restoration and cellular replacement. We aimed to investigate the correlation
      between level of circulating mobilized CD34+ hematopoietic stem progenitor cells
      (HSPCs) and viremia level in patients chronically infected with hepatitis B virus
      (HBV). METHODS: Blood samples were prospectively collected for assessing
      percentage and absolute counts of circulating CD34+ HSPCs and viral load level
      using flow cytometry and RT-PCR respectively. Patients with chronic hepatitis B
      (CHB) (n = 30), Entecavir (ETV) treated subjects (n = 30) and 20 age and gender
      matched healthy controls were enrolled in this study. Results were expressed as
      mean +/- SD. RESULTS AND DISCUSSION: A significant increase in circulating CD34+
      HSPCs level was observed in CHB patients (5 +/- 3.1, 324 +/- 195 * 103/ml) as
      compared to ETV treated subjects (0.57 +/- 0.27,1022 +/- 325) and healthy
      controls (0.53 +/- 0.37, 694 +/- 254, P < 0.001) in regards to percentage and
      absolute counts respectively. Levels of CD34+ HSPCs strongly and positively
      correlated with HBV DNA viral load levels in CHB patients (r2 = 0.8417, 0.649, P
      < 0.001).Thus, in chronic liver disorders (CHB), when reduced regenerative
      capacity of hepatocytes is reached, BMSCs mobilization occurs and their level
      increases in peripheral blood. The level of circulating CD34+ cells in peripheral
      blood of CHB patients paralleled with the hepatitis B viral load.

PMID- 29461204
TI  - SAC1 degrades its lipid substrate PtdIns4P in the endoplasmic reticulum to
      maintain a steep chemical gradient with donor membranes.
AB  - Gradients of PtdIns4P between organelle membranes and the endoplasmic reticulum
      (ER) are thought to drive counter-transport of other lipids via non-vesicular
      traffic. This novel pathway requires the SAC1 phosphatase to degrade PtdIns4P in
      a 'cis' configuration at the ER to maintain the gradient. However, SAC1 has also
      been proposed to act in 'trans' at membrane contact sites, which could oppose
      lipid traffic. It is therefore crucial to determine which mode SAC1 uses in
      living cells. We report that acute inhibition of SAC1 causes accumulation of
      PtdIns4P in the ER, that SAC1 does not enrich at membrane contact sites, and that
      SAC1 has little activity in 'trans', unless a linker is added between its ER
      anchored and catalytic domains. The data reveal an obligate 'cis' activity of
      SAC1, supporting its role in non-vesicular lipid traffic and implicating lipid
      traffic more broadly in inositol lipid homeostasis and function.

PMID- 29461206
TI  - Oral Immunotherapy With Egg and Milk: Changes in Peripheral Serum Cytokines Are
      Not Predictive Factors for Severe Adverse Reactions or for the Final Report.
AB  - BACKGROUND: Oral immunotherapy (OIT) is a new approach in patients with food
      allergy. Various immunological mechanisms underlie the reversal of food allergy.
      In this paper, we study possible changes in peripheral cytokine patterns during
      OIT. METHODS: Determinations of cytokines in peripheral blood were made in
      children who had milk or egg allergy and who received OIT. The determinations
      were made before and after OIT, and again following a final repeat oral challenge
      a month after a diet excluding the culprit food. RESULTS: No significant changes
      were registered in the cytokines studied (IL-2, IL-4, IL-6, IL-10, IL-12, IL-17,
      IFNgamma, and TNF) at any of the 3 time points. Similarly, no differences in
      cytokine pattern were observed between children who had presented anaphylaxis
      during OIT and those who overcame or did not overcome the final oral challenge.
      DISCUSSION: Peripheral cytokines do not undergo significant changes during the
      OIT process. They are not predictors of serious adverse reactions or the final
      result of the OIT.

PMID- 29461208
TI  - Death due to Live Bee Acupuncture Apitherapy.

PMID- 29461207
TI  - Evaluation of an Online Educational Program for Parents and Caregivers of
      Children With Food Allergies.
AB  - BACKGROUND AND OBJECTIVE: The increasing prevalence of food allergy affects both
      patients and their families. Objective: The aim of this study was to evaluate the
      impact of an online educational program designed for parents and caregivers of
      children with food allergies. The program was developed by a multidisciplinary
      group comprising health care professionals, researchers, and expert patients
      under the participatory medicine model. MATERIAL AND METHODS: Participants took a
      2-week online educational program covering major topics in food allergy
      management. General knowledge about the disease, symptoms, treatment, and topics
      relevant to families' daily lives were evaluated. The contents included
      educational videos, online forums, and live video chats. A pretest/posttest
      questionnaire survey was used to evaluate the impact of the program. RESULTS: A
      total of 207 participants enrolled in the educational program, which was
      completed by 130 (62.8%). Knowledge acquisition improved significantly following
      participation in the program in 15 out of 30 items (50%), reaching P<.001 for 8
      items (26.7%). Of the 207 participants who started the program, 139 (67.1%)
      visited online forums, and 27.5% attended video chats. Average overall
      satisfaction with the educational program was 8.78 (on a scale of 0 to 10).
      CONCLUSIONS: The results obtained show that parents improved their knowledge in
      all areas of food allergy. The high level of satisfaction among participants
      suggests that digital learning tools are effective and motivational, enabling
      patients to acquire appropriate knowledge and thus increasing their quality of
      life.

PMID- 29461209
TI  - Dermatitis Caused by Ingestion of Chia Seeds.

PMID- 29461205
TI  - PTEN negatively regulates the cell lineage progression from NG2+ glial progenitor
      to oligodendrocyte via mTOR-independent signaling.
AB  - Oligodendrocytes (OLs), the myelin-forming CNS glia, are highly vulnerable to
      cellular stresses, and a severe myelin loss underlies numerous CNS disorders.
      Expedited OL regeneration may prevent further axonal damage and facilitate
      functional CNS repair. Although adult OL progenitors (OPCs) are the primary
      players for OL regeneration, targetable OPC-specific intracellular signaling
      mechanisms for facilitated OL regeneration remain elusive. Here, we report that
      OPC-targeted PTEN inactivation in the mouse, in contrast to OL-specific
      manipulations, markedly promotes OL differentiation and regeneration in the
      mature CNS. Unexpectedly, an additional deletion of mTOR did not reverse the
      enhanced OL development from PTEN-deficient OPCs. Instead, ablation of GSK3beta,
      another downstream signaling molecule that is negatively regulated by PTEN-Akt,
      enhanced OL development. Our results suggest that PTEN persistently suppresses OL
      development in an mTOR-independent manner, and at least in part, via controlling
      GSK3beta activity. OPC-targeted PTEN-GSK3beta inactivation may benefit
      facilitated OL regeneration and myelin repair.

PMID- 29461210
TI  - Two Faces of LRBA Deficiency in Siblings: Hypogammaglobulinemia and Normal
      Immunoglobulin Levels.

PMID- 29461211
TI  - Vertebrate Tropomyosin as an Allergen.

PMID- 29461212
TI  - B-cell Deficiency: A De Novo IKZF1 Patient and Review of the Literature.

PMID- 29461213
TI  - Anaphylaxis Induced by Conlinin, a 2S Storage Protein in Flaxseed.

PMID- 29461214
TI  - Clinical Profile of Lipid Transfer Protein Syndrome in a Mediterranean Area.

PMID- 29461215
TI  - Paramagnetic Contrast Media: Hypersensitivity and Cross-Reactivity.

PMID- 29461216
TI  - Acquired Angioedema With Anti-C1-inhibitor Autoantibodies During Assisted
      Reproduction Techniques.

PMID- 29461217
TI  - Cross-reactivity Between nsLTPs From Cucurbitaceae Peels.

PMID- 29461218
TI  - Evidence of a cumulative effect for risk factors predicting low bone mass among
      male adolescent athletes.
AB  - BACKGROUND: Limited research has evaluated risk factors for low bone mineral
      density (BMD) in male adolescent athletes. AIMS/OBJECTIVES: To evaluate
      predictors of low BMD (defined as BMD Z-score <-1.0) in a sample of male
      adolescent distance runner and non-runner athletes. METHODS: Male adolescent
      athletes completed a survey characterising sports participation, nutrition,
      stress fracture history, dual energy X-ray absorptiometry (DXA)-measured BMD and
      body composition. Independent t-tests and analysis of covariance (ANCOVA)
      evaluated group differences; logistic regression evaluated low BMD risk factors.
      RESULTS: Runners (n=51) exhibited a lower body weight (p=0.02), body mass index
      (BMI) (kg/m2) (p=0.02), per cent expected weight (p=0.02) and spine BMD Z-score
      (p=0.002) compared with non-runners (n=18). Single risk factors of low BMD
      included <85% expected weight (OR=5.6, 95% CI 1.4 to 22.5) and average weekly
      mileage >30 in the past year (OR=6.4, 95% CI 1.5 to 27.1). The strongest two
      variable and three-variable risk factors included weekly mileage >30+ stress
      fracture history (OR=17.3, 95% CI 1.6 to 185.6) and weekly mileage >30+<85%
      expected weight + stress fracture history (OR=17.3, 95% CI 1.6 to 185.6),
      respectively. Risk factors were cumulative when predicting low BMD (including
      <85% expected weight, weekly mileage >30, stress fracture history and <1 serving
      of calcium-rich food/day): 0-1 risk factors (11.1%), 2 risk factors (42.9%), or 3
      4 risk factors (80.0%), p<0.001). CONCLUSIONS: Male adolescent runners exhibited
      lower body weight, BMI and spine BMD Z-score values. The risk of low BMD
      displayed a graded relationship with increasing risk factors, highlighting the
      importance of using methods to optimise bone mass in this population.

PMID- 29461219
TI  - MODIFIED ANTEROLATERAL SURGICAL APPROACH IN TOTAL HIP REPLACEMENT.
AB  - In this paper, we have studied the difference between classic Watson Jones
      anterolateral approach and modified anterolateral approach started in our
      institution from 2004 y. in group of patients with BMI more then 30 - 412
      patients, mean age was 66,5 y., male -157 (38.2%), female - 255 (61,8%). Primary
      diagnosis were: Idiopathic osteoarthritis - 379 (92%), Rheumatoid ostheoarthritis
      - 16 (4%), DDH - 12 (3%). All surgeries were performed on supine position. All
      surgeries were performed by single surgeon. In 321 (78%) of cases modified
      approach was used. Only uncemented implants from Zimmer-Biomet were used. In our
      study we conclude that the differences between these two approaches were hip
      flection, gluteus medius partial detachment and oblique incision of the skin, but
      these three point makes the approach much more easier to perform because in
      flexed position M.Gluteus Medius and M. Tensor Fascia Lata are more relaxed and
      in 4th position oblique incision protects the skin from damage caused by femoral
      rasp.

PMID- 29461220
TI  - INDEXES OF CYTOKINE PROFILE OF BLOOD IN PATIENTS WITH COMPLICATED ERYSIPELAS.
AB  - The cytokine blood profile in patients with complicated erysipelas was
      investigated. It was found that in patients with complications of erysipelas
      (gangrene, phlegmon, abscess, thrombophlebitis of the subcutaneous veins of the
      shin) levels of pro-inflammatory cytokines IL-1beta, TNF-alpha, IL-2, IL-6 in
      serum significantly increase and level of anti-inflammatory cytokine IL-4
      increases slightly, as well as was found a significant increase in coefficients
      reflecting the ratio of pro-inflammatory and anti-inflammatory cytokines, which
      indicates the prevalence in the blood of examined patients with complications of
      erysipelas an anti-inflammatory properties. A more significant increase in pro
      inflammatory cytokines serum levels is typical for patients with destructive
      forms of erysipelas - phlegmonous and gangrenous, a slight increase - for
      patients without purulent-necrotic component of complication (thrombophlebitis of
      the subcutaneous veins of the shin). In the future we plan to study
      pharmacological correction of shifts in cytokine blood profile with drugs with
      immunomodulating properties in patients with complicated erysipelas.

PMID- 29461221
TI  - BILATERAL ADRENOCORTICAL CARCINOMA: CASE REPORT AND REVIEW OF LITERATURE.
AB  - Adrenocortical carcinoma is a very rare and aggressive endocrinological
      malignancy arising from the adrenal cortex. The estimated incidence is 1 per
      million people, with an estimated 5-year survival rate of 16-47%. It can be
      bilateral in roughly 2-10% of cases, but the data is scarce and there is no
      conclusive evidence whether the contralateral mass is an independent tumor or a
      metastasis from the other adrenal gland cancer. Radical surgical excision is the
      only curative treatment. Therefore, careful pre- and intraoperative surgical
      planning is critically important. Open adrenalectomy has historically been the
      gold standard approach for surgical treatment of adrenocortical carcinoma.
      Laparoscopic adrenalectomy has emerged as a minimally invasive alternative, but
      its oncological safety and effectiveness has long been under debate. Current
      evidence suggests that in experienced hands laparoscopic adrenalectomy is as safe
      and effective as its open counterpart in the treatment of localized
      adrenocortical carcinoma and the adrenal masses <=10 cm. Urologists have been
      tempted to apply laparoscopy also to bilateral disease, although the need to
      reposition the patient and a longer operative time can be limitations. Given the
      rarity of adrenocortical carcinoma and the lack of quality evidence for the
      bilateral disease, we used the conventional narrative strategy to review the
      available literature. We also report a case of nonfunctioning bilateral
      adrenocortical carcinoma in a 65-year old man, who was operated on with
      simultaneous bilateral laparoscopic adrenalectomy for suspected localized (stage
      2) disease, which proved to be bilateral locally advanced carcinoma (stage 3).
      Postoperatively, the disease rapidly progressed to the fatal outcome. The case
      once again highlights the importance of detailed operative planning and the need
      of imaging studies as close as possible to the date of planned surgery.

PMID- 29461222
TI  - PECULIARITIES OF THE OCCLUSION FORMATION IN DENTAL IMPLANT SUPPORTED ARTIFICIAL
      TEETH.
AB  - The aim of this study was to assess and develop an effective computer technology
      assisted method for improved treatment of dental implant patients. Both an
      experimental and clinical assessments were conducted. The experimental part was
      performed to develop the mathematical models for calculating and analyzing the
      tensely deformed condition (TDC) in the system "non-removable prosthesis - dental
      implant - lower jaw " (PIJ). Clinical study was conducted on 76 patients with
      previously placed dental implant supported prostheses in the posterior parts of
      the lower jaw (with and without signs of bone receding around the implants)
      allocated into three groups. Results of the study allowed the authors to suggest
      an effective computer technology supported method for assessing the required
      angles of dental implants, which provides an opportunity for individual
      calculation of the dental implant in the bone of the mandible depending on the
      direction of functional load.

PMID- 29461223
TI  - NON-REMOVABLE DENTURE PROTOTYPES, EFFECTIVE IN DENTAL IMPLANTATION.
AB  - Temporary prosthesis transformed into a prosthetic prototypes and manufactured by
      CAD/CAM technologies (computer copy milling) are used to specify the final form
      of future permanent restoration and to correct occlusal relationships, vertical
      size of non-removable dentures, and their occlusal surfaces. A progressive
      loading on bone tissue in the implantation area and soft tissues formation, have
      been assessed. In this regard, the choice and placement of temporary mini
      implants, as the supports for non-removable denture prototypes for the period of
      osseointegration of two-stage intraosseous dental implants, are the issues of
      great importance. Temporary dental implants are the object of complex loads of
      different magnitude, duration and direction. The action of the prosthesis is
      closely related to load delivery to the surface of dental implant between the
      components of the system - "implant-temporary prosthesis". According to the study
      results, minimization of the momentum acting on temporary implants in the
      mesiodistal direction allows reducing stress level in the areas of permanent
      implant placement.

PMID- 29461224
TI  - [MICROECOLOGICAL CHANGES IN THE INTESTINE AND ITS EFFECT ON THE CONDITION OF HARD
      TISSUES OF TEETH IN ADOLESCENCE].
AB  - On the background of microecological changes in the gastrointestinal tract,
      mineral and protein metabolism is disrupted, biochemical changes occur in the
      phosphorus-calcium metabolism in the bones of the skeleton and hard tissues of
      the teeth. The aim of the research was to study the activity of the caries
      process, characterized by progressive decalcification, under conditions of
      microecological changes in the intestine and its effect on the processes of
      endogenous calcium assimilation in adolescence. Within the frames of the research
      68 adolescents aged 11 to 17 years with various degrees of pathology of the
      gastrointestinal tract were examined. The data of the performed studies showed
      that in patients with more severe changes in the intestinal micro flora, the
      prevalence and intensity of dental caries are significantly higher (83.4% on
      average DMFT 5.0) than in adolescents with mild dysbiosis (71.8% DMFT 3.2% ), and
      in the patients with normal intestinal micro flora - the parameters were minimal.
      Estimating and comparing the interrelation between the incidence of caries and
      the presence of diseases of the gastrointestinal tract in adolescents, a directly
      proportional dependence of the DMF index on age was found, but the greatest
      increase in the individual level of incidence of dental caries (SIC) was observed
      in adolescents aged 14-16 (SIC=0,42) with severe gastrointestinal pathology GIT.
      Thus, significant changes in dental status detected in adolescents with pathology
      of the gastrointestinal tract confirm the validity of complex treatment and
      preventive dental care, considering the processes occurring in the body and the
      oral cavity, as well as the systematic, purposeful dental care and the allocation
      of patients with gastrointestinal pathology (GIT) in a separate group.

PMID- 29461225
TI  - CHARACTERISTICS OF EMG-ACTIVITY OF MASTICATORY MUSCLES IN FUNCTIONAL TREATMENT OF
      PATIENTS AT RETENTION STAGE.
AB  - : The aim of the research was to study changes of EMG-activity of masticatory
      muscles after functional therapy at the retention stage after active orthodontic
      treatment. MATERIAL AND METHODS: The study included 55 people at the beginning of
      the retention stage after active orthodontic treatment. Patients of the study
      group were carried out functional therapy using proposed appliance during 3
      month. The control group used the standard retention method. Clinical examination
      and EMG of masticatory muscles was performed to all patients at the beginning of
      the retention and in tree months. RESULTS AND CONCLUSION: In 3 month of
      functional correction EMG-activity of the masticatory muscles significantly
      decreased and became synchronous and symmetrical in patients of the study group,
      that proved the effectiveness of the method of functional therapy at the
      beginning of retention stage after active orthodontic treatment.

PMID- 29461226
TI  - CORRELATION BETWEEN THE ORAL HYGIENIC CONDITION AND PSYCHO-SOCIAL FACTORS IN THE
      ELDERLY POPULATION OF IMERETI.
AB  - The purpose of the study is to determine the correlation between the oral
      hygienic condition and the psycho-social factors in the elderly population of
      Imereti. The research was based on the findings of 374 persons who were older
      than 50 years of age from the contingent of Kutaisi Regional Dental Center and
      From the contingent of the boarding house of the Kutaisi elderly and disabled
      people. The oral hygienic level was determined by the method of GreeneVermilion,
      and we used the E. Ambjornsen method to evaluate hygienic conditions of removable
      prostheses. The difference between the groups was determined by F Fischer's
      criterion; The relationship between the factors was determined by the correlation
      analysis - the Spearerman's Rank Test. Correlation analysis shows the level of
      hygiene and behavioral factors that show positive correlation with good hygienic
      levels of the mouth: self-efficiency r=0.113; P=0.029; Self control r=0.104;
      P=0.045; Optimism r=0.144; P=0.005; Social opportunities r=.144; P=0.005;
      Psychosocial function r=0.227; P=0.000; Self-service r=0.127; P=0.014; Motor
      function r=0.128; P=0.013; Reliable positive correlation with a bad hygienic
      level - the need for other medical assistance - r=0.327; P=0.000; Disorders of
      behavior - r=0.378; P=0.000; Chronic pain - r=0.484; P=0.000; Decreased mobility 
      r=0.492; P=0.000; Inconvenience - r=0.533; P=0.000; Physical weakness - r=0.487;
      P=0.000; Disorientation - r=0.403; P=0.000; Bad memory - r=0.417; P=0.000;
      Psychological weakness - r=0.462; P=0.000; Lack of support - r=0.318; P=0.000;
      The oral hygienic level in elderly persons correlates with psycho-social and
      behavioral factors.

PMID- 29461227
TI  - [THE DIFFERENTIATED APPROACH TO PREVENTION OF NEURAL TUBE DEFECTS IN CHILDREN].
AB  - Neural tube defects occupy second place in frequency after the defects of the
      cardiovascular system. The folate metabolism violation and hyperhomocysteinemia
      in women are proved to be the leading risk factors for the NTD of the fetus.
      Polymorphism of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) is a
      genetic determinant of folate metabolism violation. Admission of folic acid in a
      standard dose of 0.4 mg and / or the use of fortified foods does not allow
      reaching the protective level of folic acid if there is a mutation of the MTHFR
      gene or when several risk factors combine, which requires a higher dose of folic
      acid. The aim of the study is to develop an algorithm for the identification of
      women of reproductive age with the risk of having a child with NTD and to apply
      differentiated approach to the choice of a preventive dose of folic acid. A
      retrospective analysis of NTD cases in the Odessa region (Ukraine) for 2000-2013
      was carried out. The frequency of the birth of children with CNS defects and NTD,
      risk factors of NTD in children were studied. Mothers and their children with NTD
      were evaluated for the level of folic acid, homocysteine and the presence of
      C677T and A1298C MTHFR polymorphisms. The incidence of spina bifida aperta is 4.9
      per 10,000 newborns. Two groups of significant risk factors for the NTD in
      children were identified: 1) risk factors that can be eliminated - the absence of
      preconceptional prevention of NTD with folic acid (AR 0.4), second-hand tobacso
      smoking (AR 0.33), fever/hot baths in the first trimester of pregnancy (AR 0.64),
      use of well water for cooking (AP 0.44); 2) risk factors that can not be
      eliminated, and which indicate a genetic risk of NTD - a family history of a
      stroke, heart attack, thrombosis, congenital malformations, malignant tumors (AR
      0.54-0.7), an obstetrical history of miscarriage (AR 0.56 ), mother's diseases
      (varicose disease, obesity), NTD in other children in this family (AR 0.74). The
      mothers of children with NTD showed a decreased level of folic acid and an
      increased level of homocysteine in addition to the correlation of
      hyperhomocysteinemia with the mutations of the MTHFR gene. The algorithm for
      assessing the individual risk of having a child with NTD includes the evaluation
      of risk factors. If a genetic factor of folate metabolism violation or
      environmental risk factors that can not be eliminated are found, we recommend an
      additional examination. It includes determining the level of homocysteine and the
      MTHFR polymorphisms (in the case of hyperhomocysteinemia), which will identify
      the required dose of folic acid.

PMID- 29461228
TI  - A STUDY OF ADAPTIVE REACTIONS OF THE CARDIORESPIRATORY SYSTEM IN PSYCHOEMOTIONAL
      STRESS CONDITIONS.
AB  - The article presents modern data on the physiological mechanisms study of the
      stress resistance development, which occurs in medical students in the dynamics
      of studying in higher educational institution in junior courses (1-3 courses).
      The adaptive reactions of the cardiorespiratory system in conditions of
      psychoemotional load were studied. Results showed that development of adaptation
      syndrome in those conditions greatly depends on speed of formation and intensity
      level of intersystem integration in cardiorespiratory system. That relation is
      revealed most of all on the background of physical activity (load on bicycle
      ergometer to the full). The variability of stages of adaptation development was
      found out. In first group of students the first stage of adaptive syndrome is
      characterized by activation of non-specific adaptive mechanisms (1st year of
      studies), that is naturally replaced by second stage - specific adaptive
      reactions, when the intellectual work capacity increases on the background of
      rationalization of its autonomic supply. In second group of students the second
      variant of adaptation development occurs - non-specific adaptive mechanisms (1st
      stage) on the 2nd year of study are changed by the stage of specific adaptation
      (2nd stage), that is accompanied by excessive psychophysiological indexes. On the
      3rd year of study it leads to the depletion of adaptive capabilities (3rd stage).
      In third group of students the stage of activation of non-specific adaptive
      mechanisms was rapidly changed by their depletion, that was accompanied by
      decrease of intersystem integration and intellectual workability. Therefore, the
      formation of adaptive optimum occurs only in 40% of students. The majority (60%)
      of students-young women show either the initially insufficient adaptive
      capabilities, or excessive adaptation. Both insufficient and excessive adaptation
      naturally leads to psychological and autonomic disorders followed by appearance
      of psychosomatic neurotic manifestations. The prospects of future research from
      our point of view should lie in further investigation of gender peculiarities of
      adaptive reactions development up to psycho-emotional stress that develops in
      conditions of studying in university. That will make an opportunity to reveal the
      features of mechanisms of resistance formation depending on gender.

PMID- 29461229
TI  - [COMPLIANCE OF DOCTORS TO PROTOCOLS IN DIAGNOSTICS AND TREATMENT OF ARTERIAL
      HYPERTENSION].
AB  - Based on the study, data on the compliance of physicians in compliance with
      national and international protocols for the diagnosis and treatment of
      hypertension based on the principles of evidence-based medicine were revealed.
      The obtained data testify to the presence of facts not observing the recommended
      protocols. In addition, on the basis of the data obtained, insufficient level of
      joint responsibility was determined, both on the part of patients and on the part
      of doctors. The result of not full compliance with the protocols for diagnosis
      and treatment of hypertension, as well as insufficient adherence to the
      principles of joint responsibility were facts not reaching the target level of
      blood pressure. This work allows us to determine the further path of development
      of studies on arterial hypertension and ensuring all levels of prevention.

PMID- 29461230
TI  - [CLINICAL AND PSYCHOLOGICAL CORRELATIONS IN FIBROMYALGIA PATIENTS].
AB  - The features of clinical symptoms, neurotic disorders and the level of subjective
      control were studied in patients with fibromyalgia. The analysis of relationship
      between the level of subjective control and neurotic symptoms (asthenia,
      depression, anxiety, hypochondria) depending the severity of main clinical
      manifestations of the disease was carried out. It was found that high intensity
      of fatigue, muscle pain, stiffness, insomnia, and an increase in the number of
      diagnostic tender points contribute to the formation of inverse correlation
      between the level of subjective control and neurotic disturbances. Thus, the
      increase of the externality of the level of subjective control allows indicating
      to the formation of patients' passivity in relation to their disease, the lack of
      adherence to prescribed course of treatment (low compliance). Although drug
      therapy is the main component of complex treatment of fibromyalgia patients,
      patients require significantly more - successful treatment requires active
      involvement of patients in the therapy process, as well as changes in their
      attitudes and lifestyle, which can be achieved by training in so-called "schools"
      for patients, use of psychotherapeutic methods.

PMID- 29461231
TI  - EFFICIENCY OF BIOFEEDBACK THERAPY IN COMPLEX TREATMENT OF RHEUMATOID ARTHRITIS
      PATIENTS.
AB  - Biofeedback is the process of gaining greater awareness of many physiological
      functions primarily using instruments that provide information on the activity of
      those same systems, with a goal of being able to manipulate them at will. In this
      work, the analysis of efficiency of biofeedback therapy in treatment of patients
      suffering from rheumatoid arthritis (RA) is carried out. This analysis was
      fulfilled by studying the dynamics of clinical, laboratory and psychological
      (level of subjective control) indices and their comparison in patients of main
      and control groups before and after the treatment. During the course of combined
      therapy alongside biofeedback therapy, an analgesic and anti-inflammatory
      effects, and improved functional capabilities were noticed in the patients. Thus,
      the additional use of biofeedback mechanism in complex treatment of RA patients
      promote increased efficiency of medical and rehabilitation process and
      improvement of level of self-control in the patients.

PMID- 29461232
TI  - NEPHROPATHY IN EARLY RHEUMATOID ARTHRITIS PATIENTS: DOES A SIGNIFICANT RISK
      EXIST?
AB  - Objective of the study layed in assessment of the pathophysiological relation
      between cell-mediated immunity (tumor necrosis factor-alpha (TNF-alpha)
      inflammatory cytokine) activation and renal dysfunction in the patients with
      early rheumatoid arthritis. We analyzed the data from 35 early rheumatoid
      arthritis (RA) patients of average age of 50,71+/-2,25 years (ranged 18-76 years,
      80% of women) with 9,21+/-0,43 months mean duration of the disease by the time of
      the study initiation. Urine and blood tests were performed to verify the main
      indicators of kidney function and inflammation cytokines significant interaction.
      All signs of renal dysfunction at the baseline in the patients with early RA were
      associated with glomerular filtration rate decrease and excretion of urine
      protein increase. Dynamics of albuminuria, according to the analysis of variance
      for one-factor scheme, were significantly determined by the state of disease
      activity, reflecting the severity of joint damage. High urine beta-2
      microglobulin level was significantly associated with the expression rate of main
      inflammatory cytokines as per binary regression analysis. The obtained dependence
      showed the dynamics of expression of tubular disorders in early RA with a
      progressive deterioration which did associate with the levels of TNF-alpha
      expression, and variety of the urine misroglobulin rates in the interval 200-350
      MUg/L. Reliable correlation (r=0.51, p<0.05) between beta-2-microglobulinuria and
      TNF-alpha levels was clearly shown, revealing the relationship described by the
      formula MGU=- 81+937*log10 (TNF-alpha) as per regression analysis. The severity
      of tubular damage in early RA is associated with TNF-alpha expression, especially
      in the patients with TNF-alpha above 250 pg/mL, when microalbuminuria rates were
      significantly higher (p=0.00043). We identified robust data that in the early RA
      patients with high TNF-alpha, the number of reported cases of microalbuminuria
      was significantly higher than in those with low levels.

PMID- 29461233
TI  - PECULIARITIES OF QUALITY OF LIFE IN PATIENTS WITH GASTROESOPHAGEAL REFLUX
      DISEASE.
AB  - Many studies showed, that quality of life (QL ) is affected in case of
      gastroesophageal reflux disease (GERD). Numerous questionnaires with a wide
      variety of characteristics have been developed for the assessment of GERD. The
      current study aimed to determine the QL changes of patients with GERD. The sample
      consisted of 100 patients with GERD. We also formed control group, which consist
      of 50 practical healthy patients (without GERD). In case group we formed two
      subgroups- GERD with Esophagitis and GERD without Esophagitis. For QL measure we
      used SF-36 questionnaire. In case group 58 patients were male and 42 were female.
      GERD without Esophagitis subgroup included 71 cases, 41 of which were diagnosed
      in men and 30 in women. The mean age of this subgroup was 35.3+/-5.2 years. The
      second clinical subgroup is gastroesophageal reflux, with eosophthalic patients,
      which consisted of 29 cases. 17 patients in this subgroup were male and 12
      female. The mean age of this subgroup was 35,4+/-5,3 years. The most affected
      subscales of patients with GERD were "Role physical functioning", "General
      health", "Role emotional functioning" comparing with control group according SF
      36 questionnaire. In the case of GERD without an esophagus, the most affected
      were "Role physical functioning" and "Role emotional functioning" subscales.
      Regardless of the type of subgroup, QL "Bodily pain" and "General health"
      subscal's scores were lowIn case group patients, who have BMI>25 kg/m2 have lower
      scores of QL compared to the group GERD BMI<25kg/m2.

PMID- 29461234
TI  - [INFLUENCE OF THE METFORMIN THERAPY ON THE ACTIVITY OF ENDOTHELIAL-DEPENDENT
      MEDIATORS AMONG PATIENTS WITH ACUTE MYOCARDIAL INFARCTION AND CONCOMITANT TYPE 2
      DIABETES MELLITUS].
AB  - Aim of study- estimate the influence of the metformin therapy on the sCD40-ligand
      and sVE-cadherinlevels among patients with acute myocardial infarction and
      concomitant type 2 diabetes mellitus. The study included44patients with AMI and
      type 2 diabetes whichweredividedintotwo groupsdependingonthe glucose lowering
      drugs they have been taken: I group - 21patients who have been taken metformin;
      II group - 23patients, who have been taken short-acting insulin.
      Accordingtotheobtainedresults using of metformin as a glucose lowering drug in
      comparison with patients who have been taken short-acting insulin causes faster
      decreasing of the sCD40L level (-29,3% and -24,4% accordingly; r<0,05). Whereas
      there was no significant differencesin the dynamics of sVE-cadherinlevels (-22,4%
      and -19,2% accordingly; r>0,05). Positive influence of them et form in on thes
      CD40-ligand level probably is caused by the inhibition of the Akt-kinase
      phosphorylation responsible for the activation of the nuclear factor kappa-b
      which controls expression of the immune response genes, particulary CD40. It
      leads to the inhibition of the thrombocytes activation and differentiation of the
      monocytes to the macrophages able to product proatherogenic factors. It was
      established that metformin therapy among patients with acute myocardial
      infarction and diabetes mellitus type 2 leads to the faster decreasing of sCD40
      ligand in comparison with insulin therapy, which can contribute to the
      improvemenet of the prognosis in this cohort.

PMID- 29461235
TI  - [RELATIONSHIPS BETWEEN ADHERENCE TO MEDITERRANEAN DIET AND COMPONENTS OF THE
      METABOLIC SYNDROME IN THE KAZAKHSTANI POPULATION].
AB  - The urgency of the problem of metabolic syndrome (MS) is due to the high
      prevalence and risk of developing cardiovascular complications. Purpose of the
      study - to investigate the degree of adherence to the Mediterranean diet of the
      studied sample using the MedDietScore (MDS) questionnaire and to assess the
      association of score of MDS with the components of metabolic syndrome. A cross
      sectional study was conducted, during which a clinical, laboratory examination
      and questioning of 839 patients was carried out. For assessment of the
      relationship between the MS, its components and the average MDS score
      multivariate logistic regression analysis was used. The average score of MDS in
      the studied population was 20.91 (Me=21.00). The mean MDS score was statistically
      significantly lower in patients with MS components, compared with patients who
      did not have these components. The inverse association between adherence to the
      Mediterranean diet and the components of the MS was revealed.

PMID- 29461236
TI  - FEATURES OF EXCRETION OF MELATONIN IN URINE IN PATIENTS WITH TYPE 2 DIABETES
      MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE WITH MANIFESTATIONS OF FIBROSIS
      AND ITS RELATIONSHIP WITH CERTAIN METABOLIC AND IMMUNOLOGICAL INDICATORS.
AB  - To study the features of secretion of melatonin in the urine in patients with DM
      type 2 and NAFLD with manifestations of fibrosis and its relationship with some
      metabolic and immunological parameters, 23 patients with DM type 2 and NAFLD were
      examined. The degree of fibrosis in patients was diagnosed on the basis of static
      elastography and the study of indirect fibrosis markers 16 persons (72%)
      diagnosed with mild fibrosis (F0-F1 on METAVIR), 5 people (18.2%) - with moderate
      fibrosis (F2-F3 on METAVIR). Only 2 (8.7%) patients did not have any fibrotic
      disorders, so they were excluded from the further study. All patients underwent
      determination of melatonin excretion of albumin and in daily urine, as well as
      the determination of homocysteine in the blood. The level of excretion of
      melatonin in the urine in patients with DM type 2 and NAFLD did not depend on the
      degree of fibrosis and on the average was 89.50+/-16.66 mmol/day, which exceeded
      the reference values. It has been established that the increase in melatonin
      level in patients with DM type 2 and NAFLD is associated with the presence of
      fibrotic changes in the liver and a decrease in the activity of the inflammatory
      process. In addition, a direct correlation was found between the excretion of
      melatonin and homocysteine (r=0.43), as well as between melatonin and albumin
      excretion in the urine (r=0.20). Thus, an increased level of excretion of
      melatonin in the urine can be not only a marker of liver fibrosis, but also a
      predictor of cardiovascular disorders in patients with DM type 2 and NAFLD.

PMID- 29461238
TI  - EFFECTIVE TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTIONS WITH DIRECT ACTING
      ANTIVIRALS IN PRISONS SYSTEM.
AB  - Hepatitis C is a widespread infectious disorder, accounting for chronic hepatic
      inflammatory condition - hepatitis, hepatic cirrhosis and hepatocellular
      carcinoma throughout the world. In Georgia, where the incidence of HCV infection
      in population is highest among eastern European countries, hepatitis C represents
      one the most actual problems of healthcare system. The aim of the study was to
      identify the efficacy of antiviral therapy and management of side effects in HCV
      infected patients. In the patients under observation with type I genotype, the
      rapid viral response (RVR) was negative in 100%. End of treatment response (EOT)
      was negative in 100%, and stable viral response (SVR) was negative in 99.3%. In
      patients with type II genotype the rapid viral response (RVR) was negative in
      100%, end of treatment response (EOT) was negative in 100% and stable viral
      response (SVR) was negative in 100%. In patients with type III genotype: the
      rapid viral response (RVR) was negative in 100%. End of treatment response (EOT)
      was negative in 100% and stable viral response (SVR) was negative in 97%. Thus,
      HCV infection is widespread in correction department institutions. According to
      our study results, the final outcomes of antiviral treatment completed within the
      frames of this program, side effects developed during the course of treatment and
      their management are not significantly different from the results of antiviral
      treatment conducted in other population. Regardless of different psychological
      setting present in this type of institutions, this program is ongoing
      successfully and the observed results indicate on the importance of its
      continuation.

PMID- 29461237
TI  - [EVALUATION OF QUALITY OF LIFE IN PATIENTS WITH METABOLIC SYNDROME].
AB  - The aim of the research - to assess physical and psychological state of health of
      patients with metabolic syndrome. The total number of participants in the study
      was 300 people. All respondents were divided into three groups. The first group
      included 100 people practically healthy, the second group 100 people without MS
      and the third group 100 people with a reliable diagnosis of the metabolic
      syndrome. To assess the physical and psychological components of the QOL, the "SF
      36 Health Status Survery" questionnaire was used. The results of the study showed
      that the indices of the physical and psychological components of QOL in patients
      with metabolic syndrome were reduced by 3 (p<0.05) compared to the control group,
      which indicated the effect of the metabolic syndrome on QL. In patients with MS
      compared with the control group (1 group), the psychological component as a vital
      activity was reduced by 45%, role functioning due to emotional state by 55%,
      mental health by 33%, social functioning by 50%. The results of the questionnaire
      on the Special Questionnaire of the Hospital Scale of Anxiety and Depression
      (HADS) for the purpose of a detailed analysis of anxiety and depression showed
      that the level of anxiety and depression on the HADS scale depended on the
      duration and components of the MS. Indices of the physical and psychological
      component of QL in patients with MS significantly lower (p <0.05) comparing with
      the control group (practical healthy) and with the group without MS. The decrease
      in the physical (66.5%) and psychological (74%) state of QL health depends on the
      duration of the disease and on the components of the metabolic syndrome.

PMID- 29461239
TI  - [SECRETORY FUNCTION OF WHITE ADIPOSE TISSUE AND ADIPOKINES: BIOLOGICAL EFFECTS
      AND CLINICAL SIGNIFICANCE (REVIEW)].
AB  - In addition to accumulation and metabolism of triglycerides, white adipose tissue
      is recognized as the active endocrine organ, whose dysfunction is associated with
      the development of a wide range of diseases. The secretome of adipocytes is
      represented by a wide range of adipokines, which vary in depot and sex-specific
      manner. In addition, adipokines have diverse biological effects, correlations
      with different metabolic features and functions. In this review, the data on
      biological effects, origin and the clinical significance of adipokines are
      discussed. The influence of adipokines on metabolism, sensitivity to insulin,
      vascular homeostasis, angiogenesis, repair, inflammation and immune cells are
      shown. Visceral adipose tissue accumulation is accompanied with adipocytes
      hypertrophy and overproduction of such proinflammatory and proaterogenic
      molecules like resistin, visfatin, vaspin, tumor necrosis factor, interleukin 6,
      lipocalin, glypican 4, RBP4 etc. There is a tight correlation between these
      adipokines level and development of insulin resistance, type 2 diabetes,
      cardiometabolic complications and cancer. Thus, adipokines represent a group of
      informative biomarkers for the diagnostics of metabolic disorders and the
      prediction of the outcome of the wide range of diseases. The study of the effects
      and mechanisms of the action of adipokines is the basis for determining new
      targets for therapy.

PMID- 29461240
TI  - THE ROLE OF FRACTALKINE AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN THE PROGRESSION
      OF ASTHMA.
AB  - To improve the effectiveness of diagnosis and prediction of adverse asthma
      comorbid conditions based on research of clinical manifestations features,
      functional disorders of the airways and endothelial dysfunction. 79 patients were
      selected for the study. All the patients were divided into 3 groups: group 1 -
      patients with asthma (n-22); group II (n-24) - patients with asthma + diabetes
      mellitus type 2; group III (n-33) - patients with asthma + obesity + arterial
      hypertension (AH) and control group (n-17) - healthy people. All the patients
      underwent clinical examination. Spirography indicators were tested, and full
      patients' examination was conducted. The levels of fractalkine (CX3CL1) and
      Monocyte Chemoattractant Protein - 1(MCP-1) were determined by Enzyme-linked
      immunosorbent assay (ELISA) test using Ray Bio(r) Human Fractalkine system
      manufactured by Ray Biotech, Inc., USA; "Human MCP-1" (eBioscience, Austria),
      respectively. Statistical processing of parameters of endothelial function, MSR-1
      andCX3CL1, depending on comorbid pathology, has identified statistically
      significant elevated level of the separametersinall studied groups. The most
      pronounced changes of both parameters were registered in group 2 patients,
      indicative of the most significant manifestations of endothelial dysfunction in
      this patient group.Assessment of endothelium dysfunction markers depending on
      external respiration function was performed. It has been found out that MSR-1
      affects vital pulmonary capacity (chi2=14.466; r=0.002) and forced expiratory
      volume in 1 second (FEV1) (chi2=8.471; r=0.037). Besides, CX3CL1 exerts influence
      on these parameters as well (chi2=19.385, r=0.001); (chi2=11.476, r=0.009),
      respectively. The decrease in rate parameters, in particular, FEV1, MEF 25, MEF
      50, and MEF 75, was identified in all patient groups. Based on these data, we can
      assume that patients with a combination of asthma and diabetes mellitus type 2
      demonstrate more cases of endothelial malfunction, leading to the worsening of
      respiratory function, compared to the group with asthma, obesity and arterial
      hypertension and a group without comorbidity.

PMID- 29461241
TI  - MEASUREMENT OF PERSONAL RISK BEHAVI-OR IN OCCUPATIONAL RISK STUDIES AMONG HEALTH
      CARE WORKERS.
AB  - Risky behaviours, particularly illegal and heavily stigmatized behaviours, are
      difficult to measure through self-report in both high risk groups and the general
      population. Underreporting can result in substantially biased estimates of non
      injection drug use (IDU) risk of hepatitis C virus (HCV) infection. We
      hypothesized that asking about the existence of social networks injection drug
      use may be a useful marker of IDU. A cross-sectional survey of physicians and
      nurses was conducted in seven hospitals in Georgia. Based on survey responses
      participants were categorized into three IDU risk groups: ever used injecting
      drugs (Self IDU), reported a friend, family member or colleague used injecting
      drugs (Associate IDU), or reported neither (No IDU). Testing on anti-HCV was done
      using third generation ELISA methods. Both unadjusted and adjusted prevalence
      ratios between IDU risk groups and HCV prevalence were estimated. Of the 1312
      (82.2%) participants, 10 (0.8%), 75 (5.7%), and 1227 (93.5%) were categorized as
      Self IDU, Associate IDU and No IDU, respectively; with HCV prevalence of 20%,
      9.3% and 4.6%, respectively (p=0.016). The association was due primarily to
      women's reports. Those who reported some IDU risk were more likely to report
      other personal risk behaviors (e.g., multiple sex partners) and occupational risk
      behaviors (e.g., frequent exposure to blood and body fluids). This study
      represents a start of measurement development by assessing the potential
      usefulness of a marker to measure of IDU. Improved measurement of stigmatized
      behaviors is needed for confounding adjustment to improve estimates of
      occupational risks of blood-borne infections.

PMID- 29461242
TI  - PHOTODYNAMIC TREATMENT WITH NANOEMULSIFIED 5-AMINOLEVULINIC ACID AND NARROW BAND
      RED LIGHT FOR FIELD CANCERIZATION DUE TO OCCUPATIONAL EXPOSURE TO ULTRAVIOLET
      LIGHT IRRADIATION.
AB  - Actinic keratosis (AK) is a premalignant epithelial disease that develops on skin
      chronically exposed to ultraviolet-light. For outdoor workers, AK is an
      occupational hazard with a potential for malignant transformation into squamous
      cell carcinoma. Various topical treatments are used to treat AK's. Photodynamic
      therapy (PDT) promises the highest cure rates. We performed a prospective single
      center trial evaluating effects of PDT treatment for field cancerization due to
      occupational exposure to ultraviolet light irradiation in patients unresponsive
      to the treatment regimen with topical diclofenac gel. For PDT, a nanoemulsified 5
      aminolevulinic acid (5-ALA) formulation was combined with narrow band red light
      irradiation with a peak wavelength of 635 nm and a total light intensity of 37
      J/cm2. Clearance rate and adverse events were recorded. Thirty patients with a
      mean age of 77+/-10.5 years (26 males and 4 females) were included in the trial.
      They received between one and nine PDT sessions. Mean pain during PDT was scored
      at 6.8+/-2.8 using the visual analogue scale. Patients exhibited a mild immediate
      erythema after PDT. Among the patients, who tolerated PDT, a complete clearance
      was achieved in 93.3%, and >90% clearance - in 6.7%. Pain management was
      performed by cold-air analgesia. In conclusion, PDT with nanoemulsified 5-ALA and
      narrow band red light irradiation is an effective and safe treatment for
      occupational field cancerization without systemic toxicity. Adherence to this
      treatment is much better than to topical treatment.

PMID- 29461243
TI  - [ULTRASTRUCTURAL CHARACTERISTICS OF RATS TESTICLES UNDER SPERMATIC CORD STENOSIS
      AND AFTER BLOOD FLOW RESTORATION BY DIFFERENT METHODS].
AB  - Hemodynamic disorders in the testicles cause chronic organ hypoxia with damage of
      its stroma and seminiferous tubules, which plays a leading role in the
      pathogenesis of the testicular form of male infertility development. The aim of
      the work was to establish the features of ultrastructural reorganization of the
      testicles tissue and its vascular bed under circulatory hypoxia conditions and
      after restoration of blood flow in the organ. The study was conducted on 84 white
      adult male rats. The control group consisted of 12 intact animals. The
      experimental group was divided into 3 series: with stenosis of the spermatic cord
      (48 animals), with stenosis of the spermatic cord and its recanalization on the
      3rd day without correction (12 animals) and with stenosis of the spermatic cord
      and its recanalization with correction on the 3rd day (12 animals). Under
      conditions of dosage spermatic cord stenosis (when the ligature is applied) in
      the remote monitoring period, with electron microscopic study, were detected
      destructive changes of spermatid and spermatozoa, which were combined with
      significant focal intracellular and extracellular edema. In part of the cells
      heads were deformed, the acrosomes were sophisticated and fragmented. At one
      stage decompression of the spermatic cord (removal of the stenosing ligature on
      the third day), the above-described changes in accordance were deepened. At 14th
      day of the observation, collagen fibers and an electron-transparent amorphous
      component were found in the perivascular space. When the proposed method of dosed
      decompression of the spermatic cord (successive removal of three stenosing
      ligatures of different diameters) has been applied changes in the testicles
      parenchyma and its intraorganic vessels were less severe. Functional activity of
      the testicle after correction of reperfusion changes, was not significantly
      affected, what was proved by the presence in seminiferous tubules lumen of
      spermatozoa mature forms.

PMID- 29461244
TI  - EFFECT OF FREE RADICALS ON CALCITONIN-GENE-RELATED PEPTIDE MEDIATED VASODILATION.
AB  - It is known that in some pathological conditions, due to the formation of a large
      number of free oxygen radicals, the cardiovascular system is severely affected.
      However, the effect of free radicals on CGRP-mediated vasodilation remains
      unclear. The aim of this work was to study the effect of free radicals on CGRP
      mediated neurogenic vasodilation on preparations of an isolated rabbit lingual
      artery. The experiments were performed on the lingual artery preparations of 6
      rabbits of the Chinchilla breed of both sexes. The contractile-relaxation
      activity of isolated preparations, both with intact endothelial layer and
      deendotelized, were studied in isometric mode on a strain-gauge unit using
      mechanotrons of the 6 MX1C type. Our experiments showed that free radicals can
      disrupt the reactivity of the vascular wall both in the presence and in the
      absence of endothelium-dependent relaxation factors and that is might be
      considered as a main conclusion of this study.

PMID- 29461245
TI  - [IMMUNOMORPHOLOGICAL ASPECTS OF BACTERIAL SENSITIZATION IN THE EXPERIMENT].
AB  - This study investigates the morphological structure of lungs, liver and kidneys
      of the experimental animals. To reproduce the inflammation in maxilla-facial
      region under the periosteum of guinea pigs' mandible a suspension of S.aureus was
      inoculated. The infected site was exposed by a constant electric current of
      positive polarity of 5-10 MUA strength. Allergotests were used to determine the
      level of sensitization. Structural changes in the organs were determined by
      microscopic examination. The results of the study showed that as the contact with
      the antigen increased, the number of positive allergic tests also increased.
      Histologically, a generalized damage to the microstructure of the internal
      organs, depending on the degree of bacterial sensitization of the animals was
      observed.

PMID- 29461246
TI  - NEW TEMPERATE ENTEROCOCCUS PHAGE VB_GEC_EFS_2 WITH POTENTIAL OF LYSOGENIC
      CONVERSION.
AB  - Bacteriophages represent the widest group of viruses, from which only virulent
      phages are used as antibacterial agent. But the picture in the case of temperate
      phage is absolutely different; many lysogenic phages express gene products that
      have subtle effects on the phenotype of the host cell. This process is called
      lysogenic conversion. In present study we characterized new temperate
      Enterococcus faecium phage vB_GEC_EFS_2, which was isolated from river Mtkvari.
      The phage is a member of Siphoviridae family. Whole genome of phage vB_GEC-EfS_2
      was sequenced and analyzed. Total length of the genome of phage vB_GEC_EFS_2 is
      38 508bp, The assembly contains 65 ORFs, among them - 3 lysis genes , genes coded
      13 structural proteins, 1 DNA replication-associated gene, 1 gene coded
      integration, 3 - lysis-lysogenic cycle regulation, 43 hypothetical proteins. One
      holin gene contained "Haemolysin XhIA" domain which is surface associated
      haemolisyn. We isolated and purified holin gene and determine its haemolitic
      activity alongside with vB_GEC_EfS_2 phage lysate. We clarified the XhIA domain
      function and role in protein's haemolytic nature and described another kind of
      lysogenic conversion.

PMID- 29461247
TI  - [ALKALOIDS OF UNDERGROUND PARTS OF GEORGIAN FLORA'S ACONITUM ORIENTALE MILL. AND
      ACONITUM NASUTUM FISCH. EX REICHEMB AND THEIR BIOLOGICAL ACTIVITY].
AB  - The aim of research was to study underground parts of Aconitum orientale Mill and
      Aconitum nasutum Fisch exReichemb for the composition of biological active
      diterpenic alkaloids. The research object was underground parts of Aconitum
      species. Alkaloids sum was received from raw-material which was alkalined
      beforehand with chloroform extraction. From the results of research we
      established, that both species of Georgian flora's Aconitum contains alkaloids:
      lappaconitine, aconitine, karakoline. Underground parts of Aconitum orientale and
      Aconitum nasutum differ from eath other with composition of alkaloids spectrum.
      Underground parts of Aconitum orientale contains bases: ranaconitine,
      gigactonine, licoctonine, but underground parts of Aconitum nasutum contains:
      talitizamine, kamakonine, aconosine. Alkaloids' summary substances, which were
      received from underground parts of Aconitum species spread in Georgia, showed
      selective cytotoxic activity towards A-549 (lung carcinoma), DLD-1 (intestine
      adenocarcinoma), WS-1 (human normal fibroblasts).

PMID- 29461248
TI  - [RESTORATION OF SYMPATHO-PARASYMPATHETIC BALANCE IN HEART RATE VARIABILITY IN THE
      DEVELOPMENT OF PSYCHOEMOTIONAL STRESS AGAINST THE BACKGROUND OF TAURINE IN
      EXPERIMENT].
AB  - In this fragment of the study, the change in the ratio of low (LF) and high
      frequency (HF) waves to the heart rhythmogram during prolonged immobilization (5
      hours) of sexually mature white non-linear rats was studied by spectral analysis
      of heart rate variability, which causes psychoemotional stress and the
      accompanying vegetative equilibrium shift, indicating on the dysregulation of the
      sympatho-parasympathetic balance without and against the background of daily
      intraperitoneal injection of taurine (50 mg/kg) and its participation in the
      mechanisms of adaptive processes in the early poststress period (from 1 to 14
      days). Spectral analysis of both absolute and relative indices of the I-th group
      (stress without taurine) revealed significant shifts in the frequency spectrum.
      On the first day after immobilization, the total power of the spectrum decreased
      by 4.3%, the HF component by 33.3%, and the level of VLF and LF-components
      increased by 25.5% and 25%, respectively, compared to the norm. On the 14th day
      after the immobilization, there is a decrease in tension, but the LF component is
      still above the norm by 5%. Calculations of the percentage ratios of the absolute
      values of the spectrum at different times of the post-stress period against the
      background of taurine injection showed that in the initial stage (immediately and
      on the first day after stress) a strong shift of activity toward sympathization
      occurs, and the absolute value of LF and VLF in the spectrum increased by 23,1%
      and 10.9% respectively. However, the complete restoration of the vago-sympathetic
      balance with the daily application of taurine occurs already on the 7th day after
      immobilization. The beneficial effect of taurine on the cardiovascular system was
      revealed when examining the scatterogram of the regression dependence of the
      heart rate, which revealed a smaller variation in heart rate and its
      stabilization on the 7th day after immobilization. Thus, the use of taurine
      immediately after stressful reactions is necessary to accelerate adaptive
      processes in the early post-stress period to prevent the development of stress
      pathology.

PMID- 29461249
TI  - THE ROLE OF NON-PROFIT ORGANIZATIONS IN HEALTHCARE SYSTEM: WORLD PRACTICE AND
      GEORGIA (REVIEW).
AB  - The health care market is substantially different from other areas of the economy
      and therefore the behavior of health care providers operating in the health care
      market is different, which is mainly related to the form of ownership. If the
      market is mainly characterized by the pursuit of maximum profit, medical services
      market has for some public good features. Because of this, non-profit hospitals
      in western countries are considered as an alternative form of commercial
      hospitals. The purpose of the research was to study the role of not-for-profit
      hospitals, and in this regard examine the situation of the medical market in
      Georgia. The existing literature about non-profit hospitals, relevant legislation
      and statistical data, scientific articles, and other related works. The majority
      of the hospitals in Georgia represent profitable (commercial) organizations.
      41,1% of the hospitals owned by private insurance companies, 29,1% by
      individuals, 18,4% by other types of companies, 3,2% by other forms and 8% is
      state-owned. In contrast to this, more than 50% of the healthcare system of West
      Europe as well as USA is composed of non-profit (commercial) hospitals. In
      Georgia there is no sufficient motivation for operating of hospitals as non
      profit organizations. It is necessary to further adjust tax benefit in the Tax
      Code of Georgia and share European experiences. It is reasonable to increase the
      role of non-profit hospitals on the health care market that will increase
      accessibility to healthcare services for population and moreover. It will bring
      Georgian healthcare system close to the experience of civilized world.

PMID- 29461251
TI  - Axial propulsion with flapping and rotating wings, a comparison of potential
      efficiency.
AB  - Interest in biological locomotion and what advantages the principles governing it
      might offer in the design of manmade vehicles prompts one to consider the power
      requirements of flapping relative to rotary propulsion. The amount of work
      performed on the fluid surrounding a thrusting surface (wing or blade) is
      reflected in the kinetic energy of the wake. Consideration of the energy in the
      wake is sufficient to define absolute minimum limitations on the power
      requirement to generate a particular thrust. This work applies wake solutions to
      compare the minimum inviscid propulsive power requirement of wings flapping and
      in rotation at wing loading conditions reflective of hover through a state of
      lightly-loaded cruise. It is demonstrated that hovering flapping flight is less
      efficient than rotary wing propulsion except for the most extreme flap amplitude
      strokes ([Formula: see text]   >  160 degrees ) if operating at large wake
      wavelength. In cruise, a larger range of flap amplitude kinematics ([Formula: see
      text]  >  140 degrees ) can be aerodynamically more energy efficient for wake
      wavelengths reflective of biological propulsion. These results imply, based on
      the observed wing kinematics of continuous steady flight, that flapping
      propulsion in animals is unlikely to be more efficient than rotary propulsion.

PMID- 29461250
TI  - Ergodicity, hidden bias and the growth rate gain.
AB  - Many single-cell observables are highly heterogeneous. A part of this
      heterogeneity stems from age-related phenomena: the fact that there is a
      nonuniform distribution of cells with different ages. This has led to a renewed
      interest in analytic methodologies including use of the 'von Foerster equation'
      for predicting population growth and cell age distributions. Here we discuss how
      some of the most popular implementations of this machinery assume a strong
      condition on the ergodicity of the cell cycle duration ensemble. We show that one
      common definition for the term ergodicity, 'a single individual observed over
      many generations recapitulates the behavior of the entire ensemble' is implied by
      the other, 'the probability of observing any state is conserved across time and
      over all individuals' in an ensemble with a fixed number of individuals but that
      this is not true when the ensemble is growing. We further explore the impact of
      generational correlations between cell cycle durations on the population growth
      rate. Finally, we explore the 'growth rate gain'-the phenomenon that variations
      in the cell cycle duration leads to an improved population-level growth rate-in
      this context. We highlight that, fundamentally, this effect is due to asymmetric
      division.

PMID- 29461252
TI  - Dynamics of self-assembled cytosine nucleobases on graphene.
AB  - Molecular self-assembly of cytosine (C n ) bases on graphene was investigated
      using molecular dynamics methods. For free-standing C n bases, simulation
      conditions (gas versus aqueous) determine the nature of self-assembly; the bases
      prefer to aggregate in the gas phase and are stabilized by intermolecular H
      bonds, while in the aqueous phase, the water molecules disrupt base-base
      interactions, which facilitate the formation of pi-stacked domains. The substrate
      induced effects, on the other hand, find the polarity and donor-acceptor sites of
      the bases to govern the assembly process. For example, in the gas phase, the
      assembly of C n bases on graphene displays short-range ordered linear arrays
      stabilized by the intermolecular H-bonds. In the aqueous phase, however, there
      are two distinct configurations for the C n bases assembly on graphene. For the
      first case corresponding to low surface coverage, the bases are dispersed on
      graphene and are isolated. The second configuration archetype is disordered
      linear arrays assembled with medium and high surface coverage. The simulation
      results establish the role of H-bonding, vdW pi-stacking, and the influence of
      graphene surface towards the self-assembly. The ability to regulate the assembly
      into well-defined patterns can aid in the design of self-assembled nanostructures
      for the next-generation DNA based biosensors and nanoelectronic devices.

PMID- 29461253
TI  - Multifunctional devices based on SnO2@rGO-coated fibers for human motion
      monitoring, ethanol detection, and photo response.
AB  - In this study, we developed a multifunctional device based on SnO2@rGO-coated
      fibers utilizing plasma treatment, dip coating, and microwave irradiation in
      sequence, and finally realized highly sensitive human motion monitoring,
      relatively good ethanol detection, and an obvious photo response. Moreover, the
      high level of comfort and compactness derived from highly elastic and comfortable
      fabrics contributes to the long-term availability and test accuracy. As an
      attempt at multifunctional integration of smart clothing, this work provides an
      attractive and relatively practical research direction.

PMID- 29461254
TI  - Lesion detection and quantification performance of the Tachyon-I time-of-flight
      PET scanner: phantom and human studies.
AB  - The first generation Tachyon PET (Tachyon-I) is a demonstration single-ring PET
      scanner that reaches a coincidence timing resolution of 314 ps using LSO
      scintillator crystals coupled to conventional photomultiplier tubes. The
      objective of this study was to quantify the improvement in both lesion detection
      and quantification performance resulting from the improved time-of-flight (TOF)
      capability of the Tachyon-I scanner. We developed a quantitative TOF image
      reconstruction method for the Tachyon-I and evaluated its TOF gain for lesion
      detection and quantification. Scans of either a standard NEMA torso phantom or
      healthy volunteers were used as the normal background data. Separately scanned
      point source and sphere data were superimposed onto the phantom or human data
      after accounting for the object attenuation. We used the bootstrap method to
      generate multiple independent noisy datasets with and without a lesion present.
      The signal-to-noise ratio (SNR) of a channelized hotelling observer (CHO) was
      calculated for each lesion size and location combination to evaluate the lesion
      detection performance. The bias versus standard deviation trade-off of each
      lesion uptake was also calculated to evaluate the quantification performance. The
      resulting CHO-SNR measurements showed improved performance in lesion detection
      with better timing resolution. The detection performance was also dependent on
      the lesion size and location, in addition to the background object size and
      shape. The results of bias versus noise trade-off showed that the noise (standard
      deviation) reduction ratio was about 1.1-1.3 over the TOF 500 ps and 1.5-1.9 over
      the non-TOF modes, similar to the SNR gains for lesion detection. In conclusion,
      this Tachyon-I PET study demonstrated the benefit of improved time-of-flight
      capability on lesion detection and ROI quantification for both phantom and human
      subjects.

PMID- 29461255
TI  - Accuracy of radiotherapy dose calculations based on cone-beam CT: comparison of
      deformable registration and image correction based methods.
AB  - Radiotherapy dose calculations based on cone-beam CT (CBCT) images can be
      inaccurate due to unreliable Hounsfield units (HU) in the CBCT. Deformable image
      registration of planning CT images to CBCT, and direct correction of CBCT image
      values are two methods proposed to allow heterogeneity corrected dose
      calculations based on CBCT. In this paper we compare the accuracy and robustness
      of these two approaches. CBCT images for 44 patients were used including pelvis,
      lung and head & neck sites. CBCT HU were corrected using a 'shading correction'
      algorithm and via deformable registration of planning CT to CBCT using either
      Elastix or Niftyreg. Radiotherapy dose distributions were re-calculated with
      heterogeneity correction based on the corrected CBCT and several relevant dose
      metrics for target and OAR volumes were calculated. Accuracy of CBCT based dose
      metrics was determined using an 'override ratio' method where the ratio of the
      dose metric to that calculated on a bulk-density assigned version of the same
      image is assumed to be constant for each patient, allowing comparison to the
      patient's planning CT as a gold standard. Similar performance is achieved by
      shading corrected CBCT and both deformable registration algorithms, with mean and
      standard deviation of dose metric error less than 1% for all sites studied. For
      lung images, use of deformed CT leads to slightly larger standard deviation of
      dose metric error than shading corrected CBCT with more dose metric errors
      greater than 2% observed (7% versus 1%).

PMID- 29461256
TI  - High density nonmagnetic cobalt in thin films.
AB  - Recently high density (HD) nonmagnetic cobalt has been discovered in a nanoscale
      cobalt thin film, grown on Si(111) single crystal. This form of cobalt is not
      only nonmagnetic but also superconducting. These promising results have
      encouraged further investigations of the growth of the nonmagnetic (NM) phase of
      cobalt. In the original investigation, the cobalt film had a natural cobalt oxide
      at the top. We have investigated whether the growth of HD NM cobalt layers in the
      thin film depends on (i) a capping layer on the cobalt film, (ii) the thickness
      of the cobalt film and (iii) the nature of the substrate on which the cobalt film
      is grown. The results of such investigations indicate that for cobalt films
      capped with a thin gold layer, and for various film thicknesses, HD NM cobalt
      layers are formed. However, instead of a Si substrate, when the cobalt films are
      grown on oxide substrates, such as silicon oxide or cobalt oxide, HD NM cobalt
      layers are not formed. The difference is attributed to the nature-crystalline or
      amorphous-of the substrate.

PMID- 29461257
TI  - Atomic layer deposited high-k dielectric on graphene by functionalization through
      atmospheric plasma treatment.
AB  - Atomic layer-deposited (ALD) dielectric films on graphene usually show
      noncontinuous and rough morphology owing to the inert surface of graphene. Here,
      we demonstrate the deposition of thin and uniform ALD ZrO2 films with no seed
      layer on chemical vapor-deposited graphene functionalized by atmospheric oxygen
      plasma treatment. Transmission electron microscopy showed that the ALD ZrO2 films
      were highly crystalline, despite a low ALD temperature of 150  degrees C. The ALD
      ZrO2 film served as an effective passivation layer for graphene, which was shown
      by negative shifts in the Dirac voltage and the enhanced air stability of
      graphene field-effect transistors after ALD of ZrO2. The ALD ZrO2 film on the
      functionalized graphene may find use in flexible graphene electronics and
      biosensors owing to its low process temperature and its capacity to improve
      device performance and stability.

PMID- 29461258
TI  - Endothelial cell protein C receptor-dependent signaling.
AB  - PURPOSE OF REVIEW: Endothelial cell protein C receptor (EPCR), a transmembrane
      glycoprotein present on the surface of endothelial cells and other cell types, is
      an essential component of the protein C (PC) anticoagulant system. EPCR is also
      shown to play a critical role in mediating activated protein C (APC)-induced
      cytoprotective signaling. The purpose of this review is to outline the mechanisms
      of EPCR-dependent cell signaling and discuss recent findings made in this area.
      RECENT FINDINGS: Recent studies showed that the cleavage of protease-activated
      receptor (PAR)1 at a noncanonical site by APC-EPCR or the canonical site by
      thrombin when PC occupies EPCR induces beta-arrestin-2-mediated biased
      cytoprotective signaling. Factor VIIa binding to EPCR is also shown to induce the
      cytoprotective signaling. EPCR is found to be a reliable surface marker for
      identifying human hematopoietic stem cells in culture. EPCR, binding to diverse
      ligands, is thought to play a role in the pathogenesis of severe malaria, immune
      functions, and cancer by either blocking the APC-mediated signaling or by
      mechanisms that are yet to be elucidated. SUMMARY: Recent studies provide a
      mechanistic basis to how EPCR contributes to PAR1-mediated biased signaling. EPCR
      may play a role in influencing a wide array of biological functions by binding to
      diverse ligands.

PMID- 29461259
TI  - The flux of iron through ferritin in erythrocyte development.
AB  - PURPOSE OF REVIEW: Terminal differentiation of erythropoietic progenitors
      requires the rapid accumulation of large amounts of iron, which is transported to
      the mitochondria, where it is incorporated into heme. Ferritin is the sole site
      of iron storage present in the cytosol. Yet the role of iron accumulation into
      ferritin in the context of red cell development had not been clearly defined.
      Early studies indicated that at the onset of terminal differentiation, iron
      initially accumulates in ferritin and precedes heme synthesis. Whether this
      accumulation is physiologically important for red cell development was unclear
      until recent studies defined an obligatory pathway of iron flux through ferritin.
      RECENT FINDINGS: The iron chaperone functions of poly rC-binding protein 1
      (PCBP1) and the autophagic cargo receptor for ferritin, nuclear co-activator 4
      (NCOA4) are required for the flux of iron through ferritin in developing red
      cells. In the absence of these functions, iron delivery to mitochondria for heme
      synthesis is impaired. SUMMARY: The regulated trafficking of iron through
      ferritin is important for maintaining a consistent flow of iron to mitochondria
      without releasing potentially damaging redox-active species in the cell. Other
      components of the iron trafficking machinery are likely to be important in red
      cell development.

PMID- 29461260
TI  - Hemolysis and immune regulation.
AB  - PURPOSE OF REVIEW: Hemolytic anemias caused by premature destruction of red blood
      cells occur in many disorders including hemoglobinopathies, autoimmune
      conditions, during infection or following reaction to drugs or transfusions.
      Recent studies which will be reviewed here have uncovered several novel
      mechanisms by which hemolysis can alter immunological functions and increase the
      risk of severe complications in hemolytic disorders. RECENT FINDINGS: Plasma-free
      heme can induce the formation of neutrophil extracellular traps (NETs) through
      reactive oxygen species signaling. Although NETs protect the host against
      infections, in patients with sickle disease, they are associated with vaso
      occlusive crises. Heme may increase host susceptibility to infections by inducing
      heme oxygenase 1 (HO-1) in immature neutrophils, thereby inhibiting oxidative
      burst required for clearance of engulfed bacteria. In addition, heme impairs
      macrophage phagocytosis and microbial clearance through inhibition of
      cytoskeletal remodeling. Hemolysis can also favor anti-inflammatory immune cell
      polarization by inhibiting dendritic cell maturation necessary for effector T
      cell responses, inducing differentiation of monocytes into red pulp macrophages,
      important for iron recycling from senescent erythrocytes, and driving regulatory
      T-cell expansion through modulation of HO-1 expression in nonclassical monocytes.
      SUMMARY: Hemolysis breakdown products show remarkable effects on the regulation
      of immune cell differentiation and function.

PMID- 29461261
TI  - From dysmotility to virulent pathogens: implications of opioid use in the ICU.
AB  - PURPOSE OF REVIEW: Gastrointestinal dysmotility occurs frequently in the
      critically ill. Although the causes underlying dysmotility are multifactorial,
      both pain and its treatment with exogenous opioids are likely causative factors.
      The purpose of this review is to describe the effects of pain and opioids on
      gastrointestinal motility; outline the rationale for and evidence supporting the
      administration of opioid antagonists to improve dysmotility; and describe the
      potential influence opioids drugs have on the intestinal microbiome and
      infectious complications. RECENT FINDINGS: Opioid drugs are frequently prescribed
      in the critically ill to alleviate pain. In health, opioids cause gastric
      dysmotility, yet the evidence for this in critical illness is inconsistent and
      limited to observational studies. Administration of opioid antagonists may
      improve gastrointestinal motility, but data are sparse, and these agents cannot
      be recommended outside of clinical trials. Although critical illness is
      associated with alterations in the microbiome, the extent to which opioid
      administration influences these changes, and the subsequent development of
      infection, remains uncertain. SUMMARY: Replication of clinical studies from
      ambulant populations in critical care is required to ascertain the independent
      influence of opioid administration on gastrointestinal motility and infectious
      complications.

PMID- 29461262
TI  - Genetics of atrial fibrillation: an update.
AB  - PURPOSE OF REVIEW: Atrial fibrillation is a common cardiac arrhythmia with a high
      morbidity and mortality affecting 34 million worldwide. Current therapies are
      inadequate and often fail to directly address molecular mechanisms of the
      disease. In this review, we will provide an overview of recent advances in our
      understanding of the genetic underpinnings of atrial fibrillation. RECENT
      FINDINGS: Large-scale genetic association studies have more than doubled the
      number of genetic loci associated with atrial fibrillation during the last year.
      Studies examining how genes at or near these loci can affect the pathogenesis of
      atrial fibrillation are ongoing in cellular, animal, and computational models. In
      addition, several recent clinical studies have also demonstrated that variants at
      these loci can aid in risk stratification of patients. SUMMARY: There are now
      over 30 genetic loci associated with atrial fibrillation. A better understanding
      of how these loci relate to disease pathogenesis may provide insight into novel
      therapeutic targets and ultimately lead to improved clinical care.

PMID- 29461263
TI  - The role of feedback in ameliorating burnout.
AB  - PURPOSE OF REVIEW: Assessment of the current literature surrounding interventions
      directed toward the prevention of burnout in the field of medicine and
      particularly in anesthesiology. RECENT FINDINGS: Recently, burnout has been noted
      to lead to medication errors and subsequently increased harm to our patients. On
      a personal level, burnout can lead to depression and even suicide amongst
      physicians. Strategies to prevent burnout amongst anesthesiologists that have
      been studied in the literature include multisource feedback, mentorship and early
      recognition. SUMMARY: There remains no clear or definitive intervention to
      prevent burnout for physicians. However, changing our environment to embrace
      mentorship, the continual exchange of feedback and the fostering self-care could
      startlingly improve our work environment.

PMID- 29461264
TI  - Human milk composition and infant growth.
AB  - PURPOSE OF REVIEW: This review highlights relevant studies published between 2015
      and 2017 on human milk composition and the association with infant growth. RECENT
      FINDINGS: High-quality studies investigating how human milk composition is
      related to infant growth are sparse. Recent observational studies show that human
      milk concentrations of protein, fat, and carbohydrate likely have important
      influence on infant growth and body composition. Furthermore, some observational
      studies examining human milk oligosaccharides and hormone concentrations suggest
      functional relevance to infant growth. For human milk micronutrient
      concentrations and microbiota content, and other bioactive components in human
      milk, the association with infant growth is still speculative and needs further
      investigation. The included studies in this review are all limited in their
      methodological design and methods but have interesting potential in understanding
      infant growth. SUMMARY: Available evidence on human milk composition in relation
      to infant growth is sparse. This review summarizes recent publications
      investigating human milk composition; including micro- and macronutrients, human
      milk oligosaccharides, hormones and other bioactive components, and the
      association with infant weight, length, body mass index, and body composition.

PMID- 29461265
TI  - Severe acute malnutrition.
AB  - PURPOSE OF REVIEW: Advances in our understanding of the treatment of severe acute
      malnutrition (SAM) in a resource-limited environment are needed to improve
      outcome. RECENT FINDINGS: Ready-to-use therapeutic foods (RUTFs) made from local
      products and with reduced milk content lower costs and may be effective in older
      children. None of the therapeutic foods used to treat severely malnourished
      children correct long chain polyunsaturated fatty acid deficiencies.Routine short
      term antibiotic (amoxicillin) treatment, in the context of adequate healthcare
      supervision, does not improve the recovery rate. Long-term antibiotic
      (cotrimoxazole) treatment also does not provide significant benefit to non-HIV
      infected children.Increased pathogenic bacteria have been found in the intestinal
      microbiome of malnourished children and candidate organisms for use as probiotics
      have been identified. There is, however, no evidence to support the routine use
      of probiotics in these children. Although exocrine pancreatic function is reduced
      in malnourished children, routine pancreatic enzyme supplementation does not lead
      to accelerated recovery. SUMMARY: Alternative RUTF may provide a cheaper and more
      acceptable alternative to standard RUTF in the near future. Further research is
      needed to understand the implications of fatty acid deficiencies and dysbiosis
      that occur in malnourished children. Routine antibiotic administration in the
      appropriate setting is unnecessary.

PMID- 29461266
TI  - Use of Pocket-Sized Ultrasound Device in the Diagnosis of Shoulder Pathology.
AB  - OBJECTIVE: Musculoskeletal ultrasound imaging is increasingly being used for
      static and dynamic imaging of tendons, muscles, ligaments, and bones. New, hand
      held, pocket-sized ultrasounds are more portable and affordable. The purpose of
      this study was to evaluate the feasibility of pocket-sized ultrasound to diagnose
      shoulder pathology. DESIGN: Prospective cohort study. SETTING: Tertiary Care
      Hospital. METHODS: Ten consecutive patients (mean age 54; range 42-68 years)
      referred for a shoulder ultrasound for evaluation of shoulder pain were
      recruited. A diagnostic ultrasound was performed first with a pocket-sized
      ultrasound machine (VScan; General Electric, Northville, MI) and cine images
      saved for later review. Next, standard diagnostic ultrasound by a radiology
      technician specialized in musculoskeletal ultrasound was performed using (LOGIQ;
      General Electric, Northville, MI) ultrasound. The radiology report from the
      standard diagnostic ultrasound was used as the gold standard for diagnoses. Two
      independent evaluators, a musculoskeletal-trained radiologist and a sports
      medicine-trained physician with over 8 years of experience with musculoskeletal
      ultrasound, reviewed the images from the pocket-sized ultrasound. RESULTS: Nine
      of the studies were diagnosed with a pathologic entity during the standard
      diagnostic ultrasound and 1 was found to be normal. Diagnoses ranged from biceps
      tendinopathy, calcific tendonitis, and partial-articular-sided rotator cuff tear.
      Evaluator 1 correctly identified 7/10 diagnoses and evaluator 2 correctly
      identified 8/10 diagnoses. The evaluators also rated their confidence in
      diagnosis as 4.2/5 and the image quality as 3.7/4 from the pocket-sized
      ultrasound. DISCUSSION: The findings from this study demonstrate that pocket
      sized, hand-held ultrasound machines may be used to identify shoulder pathology.

PMID- 29461267
TI  - A Prospective Transcranial Doppler Ultrasound-Based Evaluation of the Effects of
      Repetitive Subconcussive Head Trauma on Neurovascular Coupling Dynamics.
AB  - OBJECTIVE: To determine the effects of repetitive subconcussive head trauma on
      neurovascular coupling (NVC) responses. DESIGN: Prospective cohort study
      collected between September 2013 and December 2016. SETTING: University
      laboratory. PARTICIPANTS: One hundred seventy-nine elite, junior-level (age, 19.6
      +/- 1.5 years) contact sport (ice hockey, American football) athletes recruited
      for preseason testing. Fifty-two nonconcussed athletes returned for postseason
      testing. Fifteen noncontact sport athletes (age, 20.4 +/- 2.2 years) also
      completed preseason and postseason testing. EXPOSURE(S): Subconcussive sport
      related head trauma. MAIN OUTCOME MEASURES: Dynamics of NVC were estimated during
      cycles of 20 seconds eyes closed and 40 seconds eyes open to a visual stimulus
      (reading) by measuring cerebral blood flow (CBF) velocity in the posterior (PCA)
      and middle (MCA) cerebral arteries via transcranial Doppler ultrasound. RESULTS:
      Both athlete groups demonstrated no significant differences in PCA or MCA NVC
      dynamics between preseason and postseason, despite exposure to a median of 353.5
      (range, 295.0-587.3) head impacts (>2g) over the course of the season for contact
      sport athletes. CONCLUSIONS: Within the context of growing concern over
      detrimental effects of repetitive subconcussive trauma, the current results
      encouragingly suggest that the dynamics of NVC responses are not affected by 1
      season of participation in junior-level ice hockey or American football. This is
      an important finding because it indicates an appropriate postseason CBF response
      to elevated metabolic demand with increases in neural activity.

PMID- 29461268
TI  - Unnatural Deaths of the Elderly Population of Sri Lanka: A Descriptive Analysis.
AB  - As people age, they may become more vulnerable to injury because of frailty, ill
      health, or dependency on others. Data from medicolegal death investigation
      including autopsy and statements from cases reported to 3 medicolegal units in
      Sri Lanka were analyzed in this study under the strict ethical framework. Of the
      study population, 265 were male and 75 were female. Mean age was 71.14 years.
      Commonest manner of death was accidental (62.1%) followed by suicide (32.1%) and
      homicide (5.6%). Commonest types of incidents were road traffic accidents
      (26.5%), falls (22.6%), and poisoning (21.2%). Among the road traffic accidents,
      pedestrians (77.9%) were the majority. Poisoning (59.6%) was the commonest method
      of suicide. The commonest weapons used in homicides were blunt weapons (47.3%).
      Association with alcohol was seen in more than 10% of suicidal and accidental
      deaths. More attention should be given to the elderly people who are using the
      roads while developing policies by the state. Furthermore, it is high time to
      think about psychological aspect in the elderly care management specially alcohol
      abuse and suicidal ideation among them.

PMID- 29461269
TI  - Coronary Artery Abnormalities as the Cause of Sudden Cardiac Death: A 20-Year
      Review.
AB  - In this case series, we delve into the database of medicolegal cases of the
      Forensic Pathology Department at Hamilton Health Sciences in Hamilton Ontario
      from the last 20 years (1996-2017), and review cases of sudden cardiac death due
      to coronary artery abnormalities. We found 17 cases that fit the criteria, which
      gave us an incidence of 1.34 per 1000 cases. These cases were further audited for
      age, sex, type of coronary artery abnormality, symptoms before demise,
      circumstances of death, presence of significant atherosclerotic disease, and
      toxicology. Two more recent cases underwent postmortem genetic testing, and we
      reported on the result of one of these molecular studies. In our case series, the
      most commonly affected coronary artery was the right coronary artery, with the
      most common anomaly being abnormal origin from the left sinus of Valsalva.
      Although the literature maintains that left coronary artery from the opposite
      sinus is associated with higher incidence of SCD, our study shows that RCAs from
      the opposite aortic sinus, including those deemed to be low risk by
      classification, can be causes of SCD.

PMID- 29461270
TI  - The Role of Personality in a Regular Cognitive Monitoring Program.
AB  - OBJECTIVES: This study examines the role of personality in cognitive performance,
      adherence, and satisfaction with regular cognitive self-monitoring. MATERIALS AND
      METHODS: One hundred fifty-seven cognitively healthy older adults, age 55+,
      completed the 44-item Big-Five Inventory and were subsequently engaged in online
      monthly cognitive monitoring using the Cogstate Brief Battery for up to 35 months
      (M=14 mo, SD=7 mo). The test measures speed and accuracy in reaction time, visual
      learning, and working memory tasks. RESULTS: Neuroticism, although not related to
      cognitive performance overall (P>0.05), was related to a greater increase in
      accuracy (estimate=0.07, P=0.04) and speed (estimate=-0.09, P=0.03) on One Card
      Learning. Greater conscientiousness was related to faster overall speed on
      Detection (estimate=-1.62, P=0.02) and a significant rate of improvement in speed
      on One Card Learning (estimate=-0.10, P<0.03). No differences in satisfaction or
      adherence to monthly monitoring as a function of neuroticism or conscientiousness
      were observed. CONCLUSIONS: Participants volunteering for regular cognitive
      monitoring may be quite uniform in terms of personality traits, with personality
      traits playing a relatively minor role in adherence and satisfaction. The more
      neurotic may exhibit better accuracy and improve in speed with time, whereas the
      more conscientious may perform faster overall and improve in speed on some tasks,
      but the effects appear small.

PMID- 29461271
TI  - Endothelin Signaling Contributes to Modulation of Nociception in Early-stage
      Tongue Cancer in Rats.
AB  - BACKGROUND: Patients with early stage tongue cancer do not frequently complain of
      tongue pain. Endothelin-1 signaling is upregulated in the cancerous tongue at the
      early stage. We tested the hypothesis that endothelin-1 signaling contributes to
      the modulation of tongue nociception. METHODS: Squamous cell carcinoma cells were
      inoculated into the tongue under general anesthesia. Lingual mechanical
      sensitivity under light anesthesia using forceps from days 1 to 21 (n = 8) and
      the amounts of endothelin-1 and beta-endorphin in the tongue on days 6, 14, and
      21 (n = 5 to 7) were examined after the inoculation. The effect of endothelin-A
      or u-opioid receptor antagonism on the mechanical sensitivity was examined (n = 5
      to 7). RESULTS: Lingual mechanical sensitivity did not change at the early stage
      (days 5 to 6) but increased at the late stage (days 13 to 14). The amount of
      endothelin-1 increased (25.4 +/- 4.8 pg/ml vs. 15.0 +/- 5.2 pg/ml; P = 0.008),
      and endothelin-A receptor antagonism in the tongue induced mechanical
      hypersensitivity at the early stage (51 +/- 9 g vs. 81 +/- 6 g; P = 0.0001). The
      u-opioid receptor antagonism enhanced mechanical hypersensitivity (39 +/- 7 g vs.
      81 +/- 6 g; P < 0.0001), and the amount of beta-endorphin increased at the early
      stage. CONCLUSIONS: beta-Endorphin released from the cancer cells via endothelin
      1 signaling is involved in analgesic action in mechanical hypersensitivity at the
      early stage.

PMID- 29461272
TI  - Does Aerobic Respiration Produce Carbon Dioxide or Hydrogen Ion and Bicarbonate?
AB  - Maintenance of intracellular pH is critical for clinical homeostasis. The
      metabolism of glucose, fatty acids, and amino acids yielding the generation of
      adenosine triphosphate in the mitochondria is accompanied by the production of
      acid in the Krebs cycle. Both the nature of this acidosis and the mechanism of
      its disposal have been argued by two investigators with a long-abiding interest
      in acid-base physiology. They offer different interpretations and views of the
      molecular mechanism of this intracellular pH regulation during normal metabolism.
      Dr. John Severinghaus has posited that hydrogen ion and bicarbonate are the
      direct end products in the Krebs cycle. In the late 1960s, he showed in brain and
      brain homogenate experiments that acetazolamide, a carbonic anhydrase inhibitor,
      reduces intracellular pH. This led him to conclude that hydrogen ion and
      bicarbonate are the end products, and the role of intracellular carbonic
      anhydrase is to rapidly generate diffusible carbon dioxide to minimize acidosis.
      Dr. Erik Swenson posits that carbon dioxide is a direct end product in the Krebs
      cycle, a more widely accepted view, and that acetazolamide prevents rapid
      intracellular bicarbonate formation, which can then codiffuse with carbon dioxide
      to the cell surface and there be reconverted for exit from the cell. Loss of this
      "facilitated diffusion of carbon dioxide" leads to intracellular acidosis as the
      still appreciable uncatalyzed rate of carbon dioxide hydration generates more
      protons. This review summarizes the available evidence and determines that
      resolution of this question will require more sophisticated measurements of
      intracellular pH with faster temporal resolution.

PMID- 29461273
TI  - Relationship of surgeon/hospital volume with outcomes in uro-oncology surgery.
AB  - PURPOSE OF REVIEW: Hospital and surgical volumes, as well as complications, are
      considered to influence intra and postoperative results in most surgical
      operations. This trend is also seen in uro-oncologic surgery. The objective of
      this review is to critically analyze the most recent literature to give a
      comprehensive overview on whether surgical and hospital volumes have an impact,
      and whether regionalization of the procedure should be advised. RECENT FINDINGS:
      Uro-oncologic surgery has recently become more regionalized, and data coming from
      different population-based analyses appear to support this trend. Recent data
      suggest that the most beneficial procedures could be radical cystectomy, radical
      prostatectomy, and partial nephrectomy. For radical cystectomy, even considering
      different cut-off values, saw better results for postoperative complications,
      mortality and long-term oncological and functional outcomes in patients treated
      in high-volume institutions. Centralization of radical prostatectomy seems to
      affect short-term outcomes and costs related to prostate cancer treatment, with
      high-volume institutions providing more affordable treatments reducing cancer
      recurrence and progression. Partial nephrectomy is more frequently performed in
      cT1-b cancer in high-volume than low-volume institutions. Additionally, in this
      setting it has a higher success rate and lower complications, shorter operative
      time, and fewer prolonged hospital stays. SUMMARY: Regionalization of the
      procedure in high-volume centers seems to have impact on postoperative morbidity
      and mortality for the most frequent major uro-oncological procedures: radical
      prostatectomy, radical cystectomy, and partial nephrectomy; but there are
      insufficient data available on other procedures.

PMID- 29461274
TI  - Long-term results of intestinal transplantation in children: survival after 10
      years, intestinal function, quality of life.
AB  - PURPOSE OF REVIEW: The review aims to describe in detail contemporary medical,
      nutritional, and psychosocial results in pediatric intestinal transplant (ITx)
      recipients greater than 10 years removed from their transplant, and to highlight
      significant long-term post-ITx challenges and complications. The review will draw
      from recent publications in the field, the ITx registry as well as detailed
      unpublished data from a large, well established single center. RECENT FINDINGS:
      The majority of long-term ITx survivors are off parenteral nutrition altogether,
      but a significant number require supplemental tube feeds to gain weight and grow
      properly. A number of micronutrient deficiencies are observed in long-term follow
      up. Renal insufficiency and posttransplant lymphoproliferative disorder are the
      most concerning long-term complications. Many require special education, and in
      certain domains some report lower health related quality of life. SUMMARY: For
      children more than 10 years out from ITx, growth and weight gain are sustained;
      oral aversion and dependence on supplemental tube feeds remain prevalent issues.
      Most recipients are successfully managed with frequent outpatient visits and
      multiple daily medications. Post-transplant lymphoproliferative disorder and
      chronic kidney disease are long-term concerns. Though many children require
      special education, most are high functioning and report good health-related
      quality of life.

PMID- 29461275
TI  - Management of the critically ill liver failure patient: surpassing our
      limitations to reach transplantation.
AB  - PURPOSE OF REVIEW: Patients with liver failure and liver-related diseases are
      often critically ill. Here, we review advances in donor organ management, tools
      for patient selection and highlight ICU management of liver transplant (LT)
      recipients. A focused discussion on the impact each of these factors have on
      critical care management of liver failure patients is presented. RECENT FINDINGS:
      Artificial liver assist devices to increase donor organ utilization are
      broadening the potential for transplantation of critically ill patients.
      Additionally, prognostication tools continue to improve and identify patients
      salvageable with transplantation despite severely deranged physiology. Most
      importantly, early recognition of liver failure combined with proactive critical
      care management reduces the incidence of failure-to-rescue and increases the
      likelihood of transplantation. SUMMARY: Liver transplantation is often the only
      hope for cure, and despite the presence of profound physiologic disturbances
      surgery remains the goal. In this review, we cover topics key in ICU management
      of LT recipients. A focused discussion on development of artificial liver assist
      devices to increase donor organs, prognostic scoring systems to define
      appropriate transplant recipients, critical care management of liver failure
      physiology, and bridging modalities and supportive measures are presented.

PMID- 29461276
TI  - Health surveillance for occupational asthma.
AB  - PURPOSE OF REVIEW: The outcome for workers with occupational asthma is improved
      for those with an earlier diagnosis. Health surveillance at work is in principle
      designed to identify such cases, so that the risks to the individual worker, and
      coworkers, can be reduced. There is recent evidence to suggest that the uptake
      and quality of such surveillance could be improved. This review has assessed
      current approaches to health surveillance for occupational asthma. RECENT
      FINDINGS: The article covers a review of the utility of questionnaires, lung
      function testing, immunological investigations, and other tests, including
      exhaled nitric oxide, sputum eosinophilia, and exhaled breath condensate
      specifically in the context of workplace-based health surveillance. SUMMARY:
      Questionnaires remain a key component of respiratory health surveillance,
      although maybe limited by both sensitivity and specificity for early occupational
      asthma. The role of lung function testing is debated, although is recommended for
      higher level health surveillance. Various examples of immunological testing in
      health surveillance are discussed, but more evidence is needed in many specific
      areas before more general recommendations can be made. Evidence is discussed in
      relation to the utility of newer approaches such as exhaled nitric oxide, sputum
      eosinophilia, and exhaled breath condensate.

PMID- 29461278
TI  - Home Inotropes in Patients Supported with Left Ventricular Assist Devices.
AB  - There is little data outlining the use of outpatient inotropic medications in
      patients with existing left ventricular assist devices (LVADs). This case series
      explores this patient population and seeks to define the indications,
      complications, and safety of dual support. A retrospective chart review was
      conducted for all patients on LVAD and then subsequently started on home
      inotropes post device implant. Eight patients met inclusion criteria. The
      indications for inotropes were right ventricular failure, aortic insufficiency
      with biventricular failure, LVAD thrombosis with contraindication to device
      exchange, and cannula malposition with elevated pulmonary vascular resistance.
      Mean duration of combined support was 273+/-170 days. Cardiac index improved from
      1.96 +/- 0.24 to 2.31 +/-0.35L/min/m after inotropes (p = 0.02). There was no
      change in hospital admissions. The most common reason for readmission was heart
      failure symptoms, followed by bleeding. Five patients died during the study
      period, one underwent heart transplant, and two remain on inotropic support. Home
      inotropes may be indicated in selected CF-LVAD patients with refractory right
      ventricular failure or impaired LVAD function. Inotropes can improve hemodynamics
      and provide palliation of symptoms. However, long-term inotrope use does not
      reduce hospital readmissions and is associated with multiple complications
      related to the need for an indwelling intravenous line.

PMID- 29461277
TI  - Clinical Relevance of Histopathologic Analysis of HeartMate II Thrombi.
AB  - Left ventricular assist device (LVAD) thrombosis is a devastating complication
      that occurs in about 10% of patients despite anticoagulation and antiplatelet
      treatment. How the thrombus initiates and propagates is unknown. We
      pathologically and immunohistochemically examined 28 thrombi removed from 17
      HeartMate II LVADs. Two groups of thrombi were found: those formed in the
      inlet/outlet and those on the rotor. The four thrombi found at the inlet (three
      inlet conduit and one inlet tube) and outlet (three at outlet elbow and one
      outlet graft) appeared similar and were composed of a loose meshwork of
      fibrin(ogen), von Willebrand factor, leukocytes, and aggregated platelets. The
      majority of the thrombi (20/28), however, were located on the rotor: nine at the
      inlet bearing, five on the rotor vanes, and six at the outlet bearing. Laminated
      thrombi formed around the inlet bearing in rings, an area of blood recirculation.
      The inner rings of the thrombus had fibrin and von Willebrand factor. Aggregated
      platelets were found in the outer thrombi rings, but limited evidence of
      platelets within the laminated thrombi was noted. The presence of distinct rings
      suggests development of the clot over time. The increased platelets in the outer
      rings of the inlet bearing thrombi would support further investigation into their
      role in thrombus growth. Initiating events require further investigation, but the
      fibrin-rich structure of HeartMate II thrombi suggests that alternative
      anticoagulation strategies are needed to prevent thrombosis in our LVAD patients.

PMID- 29461279
TI  - Individualized Antithrombotic Therapy in Heartware HVAD Recipients.
AB  - There are no evidence-based guidelines for antithrombotic therapy in left
      ventricular assist device patients. We evaluated the efficacy of a multi-agent,
      test-guided protocol, which remained consistent throughout our use of the
      Heartware HVAD. Thrombelastography and PFA-100 guide antiplatelet titration.
      Goals are normal kaolin thrombelastography maximum amplitude and prolonged PFA
      100. We analyzed incidence and rates of nonprocedural bleeding, stroke, and pump
      thrombosis for all 81 primary Heartware left ventricular assist devices implanted
      since 2011. For each event, we examined whether each test was within goal range.
      We also compared medication burden and dosage between patients with and without
      events. Pump thrombosis and hemorrhagic stroke each occurred in two patients
      (2.7%; 0.03 events/patient-year [EPPY]), and ischemic stroke in six (7.4%; 0.10
      EPPY). Nonprocedural bleeding occurred 75 times in 34 patients (42%; 1.24 EPPY),
      primarily gastrointestinal (28%; 0.66 EPPY). Subtherapeutic INR was the most
      common at thrombotic events; supratherapeutic partial thromboplastin time, INR,
      and PFA-ADP were common at bleeding events. Medication burden and dosage were
      lower in patients with events than in stable patients. Protocol-guided
      antithrombotic therapy resulted in low rates of pump thrombosis and hemorrhagic
      stroke. Ischemic stroke and gastrointestinal bleeding rates were higher than in a
      comparable HVAD population. Optimization of our protocol to decrease its
      complexity and to reduce bleeding is underway.

PMID- 29461280
TI  - The rationale for a role for diet and nutrition in the prevention and treatment
      of cancer.
AB  - There is considerable evidence to support dietary recommendations for prevention
      of cancer as well as for patients undergoing or recovering from cancer treatment.
      We consider here implications from human, animal and in-vitro studies of the
      effects of dietary factors (macronutrients and micronutrients-phytochemicals) on
      cancer. An important epidemiology study, the China Project found a significant
      correlation between disease incidence and markers of animal product consumption.
      Evidence of the role of animal protein in the promotion of cancer also comes from
      animal studies. Food restriction has been shown in human and animal studies to
      slow cancer progression. Phytochemicals from whole plant foods are protective
      against oxidative stress, inhibit cell proliferation, induce cell-cycle arrest,
      and apoptosis, act as antiangiogenesis factors, and inhibit cyclooxygenase-2,
      which has been related to metastasis. Some mechanisms that mediate the effect of
      diet on cancer involve cell signaling through insulin factors and mammalian
      target of rapamycin, a nutrient sensing complex related to growth, altered gene
      expression through epigenetics, and the effects of microbial metabolites produced
      by the gut microbiota that is strongly influenced by dietary factors. The
      evidence accumulating for many years indicates that diet, what we eat every day,
      can affect disease. Besides preventing the development of cancer, this could also
      be harnessed to positively influence treatment outcomes as well as prevent
      recurrence. As research strategies developed for drug studies are not
      appropriate, it is important that new methodologies be developed to study these
      effects.

PMID- 29461281
TI  - Self-assessment of Goal Achievements Within a Gynecological Cancer Rehabilitation
      Counseling.
AB  - BACKGROUND: There is an increasing focus on patient involvement in cancer
      rehabilitation. Goal assessment may improve the patient's self-management of life
      after cancer. OBJECTIVE: The aim of this study was to evaluate whether (1) nurse
      led supported goal setting and assessment of goal achievement were feasible in a
      clinical setting and (2) there was a positive association between women's goal
      achievement and their self-assessed global health status (GHS). METHODS: Women
      surgically treated for gynecological cancer were offered rehabilitation
      counseling consisting of 2 face-to-face sessions and 2 phone calls carried out by
      a nurse. The Goal Attainment Scale evaluated goal achievement, whereas GHS was
      assessed with a quality-of-life questionnaire (European Organization of Research
      and Treatment of Cancer Quality of Life Questionnaire Core 30). RESULTS: One
      hundred fifty-one women consented to participate; 70% of the women at the first
      phone call and 72% at the second phone call achieved their goals as "expected" or
      "more or much more than expected." Endometrial cancer patients more often
      achieved their goals than ovarian or cervical cancer patients. Approximately 32%
      of ovarian and 40% of cervical cancer patients scored their goal achievement
      "below expected." The patients' GHS was not associated with goal attainment
      measured at each phone call. CONCLUSION: Goal measurement is feasible in cancer
      rehabilitation, in both goal setting and goal achievement. Goal achievement less
      than expected levels in women recovering from ovarian or cervical cancer suggests
      a need for additional support. IMPLICATIONS FOR PRACTICE: This study supports
      goal setting and goal achievement as a feasible approach to improve cancer
      rehabilitation and that nursing professionals can facilitate individualized
      rehabilitation efforts.

PMID- 29461282
TI  - A Behavioral Physical Activity Intervention to Manage Moderate and Severe Fatigue
      Among Head and Neck Cancer Patients-Pre-efficacy Study in the National Institutes
      of Health ORBIT Model.
AB  - BACKGROUND: Cancer-related fatigue (CRF) reduces head and neck cancer (HNC)
      survival rates and is the most common, severe, and distressing symptom negatively
      impacting activities of daily living (ADLs) dependence among HNC patients. These
      patients remain physically inactive after their cancer treatment, although there
      is consensus that physical activity mitigates CRF in cancer patients. OBJECTIVE:
      A home-based personalized behavioral physical activity intervention with fitness
      graded motion exergames (PAfitME) was evaluated for its intervention components,
      intervention delivery mode, and intervention contact time/duration with initial
      assessment of the feasibility, acceptability, safety, and outcomes. METHODS: This
      study (N = 8) was a single-group, pre-post design to evaluate a 6-week PAfitME at
      the end of HNC treatment. Health outcomes were CRF, ADL dependence, and fitness
      performance. Behavioral outcomes were exergame adherence. RESULTS: Positive
      health and behavioral outcomes support the PAfitME protocol including
      intervention components, intervention delivery mode, and intervention contact
      times/duration. The PAfitME intervention is feasible and acceptable with
      promising adherence rates. No adverse events were reported. There was marked
      improvement in CRF, ADL dependence, cardiorespiratory fitness, balance, muscle
      strength, and shoulder forward flexion, with large to moderate effect sizes as a
      result of the PAfitME intervention. CONCLUSION: The PAfitME protocol is ready for
      additional testing in a randomized clinical trial. IMPLICATIONS FOR PRACTICE: The
      PAfitME intervention is a nurse-led nonpharmacological intervention. It can be
      integrated into home care or telehealth care for HNC patients at the end of their
      cancer treatment once effectiveness is established.

PMID- 29461283
TI  - The Impact of Education About Cervical Cancer and Human Papillomavirus on Women's
      Healthy Lifestyle Behaviors and Beliefs: Using the PRECEDE Educational Model.
AB  - BACKGROUND: Early detection of cervical cancer improves the chances of successful
      treatment. OBJECTIVE: The aim of this study was to determine the effect of
      education about cervical cancer and human papillomavirus on the healthy
      lifestyle, behavior, and beliefs of Turkish women who were without cancer, using
      the PRECEDE education model. METHODS: This qualitative and quantitative study was
      conducted as a prospective, randomized, 2-group (intervention and control) trial
      at a community training center in north Turkey. A total of 156 Turkish women who
      were without cancer participated in this study. The semistructured interview
      form, the SF-36 Health Status Questionnaire, the Health Belief Model Scale for
      Cervical Cancer and Pap Smear Test, and the Healthy Lifestyle Behavior Scale II
      were used. RESULTS: The subdimension scores of the Health Belief Model Scale for
      Cervical Cancer and Pap Smear Test were found to be higher among women in the
      study group (cervical cancer seriousness, P = .001; health motivation, P = .001)
      as compared with the control group after the education program. The SF-36 Health
      Status Questionnaire domain scores for physical role limitations, mental role
      limitations, and general health perceptions increased in the study group after
      the intervention. CONCLUSION: The posteducation health motivation of women in the
      study group was improved, the women's perceptions of obstacles to Papanicolaou
      testing decreased, and through increased knowledge and awareness, the rate of
      Papanicolaou testing increased. IMPLICATIONS FOR PRACTICE: Educational programs
      aimed at motivating women to increase their awareness of cervical cancer,
      preventing cervical cancer, and having Papanicolaou testing are necessary and
      beneficial in this sample.

PMID- 29461284
TI  - Psychometric Performance of the Arabic Versions of the Cancer Behavior Inventory
      Brief and the Functional Assessment of Cancer Therapy-Breast.
AB  - BACKGROUND: Valid and reliable instruments in Arabic are needed to measure self
      efficacy and quality of life for Arabic patients with cancer. OBJECTIVE: The aim
      of this study was to test the psychometric performance of the Cancer Behavior
      Inventory-Brief Arabic (CBI-BA), including participant understanding of items,
      and the Functional Assessment of Cancer Therapy-Breast Arabic (FACT-BA). METHODS:
      Using a cross-sectional design, 438 cancer patients completed the CBI-BA, 30 of
      whom completed cognitive interviews. A subsample 167 women with breast cancer
      also completed the FACT-BA. Internal consistency evidence was assessed with
      Cronbach's alpha and construct validity with principal axis factoring. RESULTS:
      Internal consistency estimates were acceptable for the total CBI-BA (alpha = .81)
      and FACT-BA (alpha = .88) scales. Exploratory factor analyses showed evidence of
      construct validity for the CBI-BA; 1 factor was derived, compared with four in
      the original English version. Cognitive interviews indicated satisfactory patient
      understanding of CBI-BA items. The Arabic version of the general FACT-General
      scale had 4 factors according to expectation. CONCLUSION: The CBI-BA has adequate
      psychometric performance for the measurement of self-efficacy for coping with
      cancer in Arabic patients. The FACT-General Arabic has adequate evidence of
      reliability and validity for the measurement of quality of life in Arabic women
      with breast cancer. IMPLICATIONS FOR PRACTICE: The availability of culturally
      sensitive and psychometrically sound instruments for Arabic patients diagnosed
      with cancer should be valuable for healthcare clinicians and researchers to
      assess self-efficacy for coping with cancer and quality of life.

PMID- 29461285
TI  - Gauging the Effects of Self-efficacy, Social Support, and Coping Style on Self
      management Behaviors in Chinese Cancer Survivors.
AB  - BACKGROUND: Better self-management control in cancer survivors would benefit
      their functional status, quality of life, and health service utilization. Factors
      such as self-efficacy, social support, and coping style are important predictors
      of self-management behaviors of cancer survivors; however, the impact of these
      factors on self-management behaviors has not yet been empirically tested in
      Chinese cancer survivors. OBJECTIVES: The aim of this study was to examine how
      self-efficacy, social support, and coping style affect specific self-management
      behaviors. METHODS: A secondary data analysis was completed from a cross
      sectional study. A total of 764 cancer survivors were recruited in the study.
      Validated instruments were used to assess patients' self-efficacy, social
      support, and coping style. Structural equation modeling (SEM) was used to test
      the hypothesis. RESULTS: The SEM model fits the data very well, with root mean
      square error of approximation (RMSEA) of 0.034; close-fit test cannot reject the
      hypothesis of root mean square error of approximation of 0.05 or less,
      comparative fit index of 0.91, Tucker-Lewis index of 0.90, and weighted root mean
      square residual of 0.82. For the measurement models in the SEM, all items loaded
      highly on their underlying first-order factors, and the first-order factors
      loaded highly on their underlying second-order factors (self-efficacy and social
      support, respectively). The model demonstrated that self-efficacy and social
      support directly and indirectly, via coping style, affect 3 self-management
      behaviors (ie, communication, exercise, and information seeking). CONCLUSION: Our
      results provide evidence that self-efficacy and social support impose significant
      direct effects, as well as indirect effects via copying style, on the self
      management of cancer survivors. IMPLICATIONS FOR PRACTICE: Our findings may help
      nurses to further improve their care of cancer survivors in terms of their self
      management behaviors, specifically communication, exercise, and information
      seeking.

PMID- 29461286
TI  - Recent advances in the treatment of rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: Therapies for rheumatoid arthritis (RA) continue to expand
      rapidly. The purpose of this review is to discuss novel treatment options,
      including biosimilars, that are available, as well as to highlight promising
      agents in development. The purpose is also to discuss new emerging safety signals
      associated with these drugs and to discuss strategies in tapering therapy. RECENT
      FINDINGS: There are several novel RA therapies. These include the interleukin-6
      (IL-6) receptor blocker sarilumab, which was approved in 2017. In aggregate, the
      sarilumab studies show that it is effective in RA, including patients with
      incomplete responses to methotrexate and anti-tumor necrosis factor inhibitor,
      and showing superior efficacy when used in higher dose (200 mg every 2 weeks) to
      standard-dose adalilumab. Other drugs that are currently being studied include
      the IL-6 cytokine blocker sarikumab, the small targeted molecule filgotinib, and
      many new biosimilars. Baracitinib failed to achieve approval by the Food and Drug
      Administration primarily over perceived safety concerns. The two biosimilar drugs
      currently approved are CT-P13 and SB2, which are based on the reference product
      infliximab. Although this review summarizes trials examining biologic tapering,
      additional data are needed to guide clinicians in regards to treatment de
      escalation in RA. SUMMARY: With the greatly expanded armamentarium of RA
      treatment options available, it is important for clinicians to understand the
      data regarding drug efficacy and safety. With remission increasingly attainable,
      effective drug tapering strategies are needed. Although tapering trials do exist,
      more studies will be needed to help guide clinical practice.

PMID- 29461287
TI  - Developing competent videofluoroscopic swallowing study analysts.
AB  - PURPOSE OF REVIEW: This review examines the recent literature concerning the
      development of VFSS analysts. RECENT FINDINGS: Face-to-face and blended methods
      of training improve reliability and accuracy of VFSS analysis. However, with the
      exception of the literature describing the MBSImP training, most studies
      investigate relatively brief training for specific VFSS rating tools. The
      influence of training mode and trainee factors has received limited attention.
      SUMMARY: There is a lack of controlled studies investigating the influences of
      training methods for VFSS analysis. Pilot data is emerging concerning VFSS
      analysis training 'packages' but without information about the relative influence
      of training mode, it is difficult to determine the most efficient and cost
      effective way of training VFSS analysts. Future research should investigate the
      contribution of trainee-related factors to succeed in VFSS analysis training, and
      the relative benefits and disadvantages of online, peer, independent, and blended
      modes of training.

PMID- 29461289
TI  - Evolution of a Burn Care Network.
AB  - INTRODUCTION: A private burn center started in Augusta, GA, in 1978 has expanded
      into a burn care network of 7 comprehensive burn centers. We have analyzed 2
      years of admissions to this network to assess growth and the network's level of
      participation in national burn care. MATERIALS AND METHODS: Total admissions to
      the network were quantified for years 2015 and 2016. Growth during that 2-year
      period was calculated, and the network's admissions were evaluated as a
      percentage of national burn admissions. RESULTS: Total admission for 2015 came
      from 4713 patients; 5683 patients were admitted in 2016. These totals
      demonstrated a 15% increase. The 2-year total of 10,217 admissions represented
      21% of the 46,892 burn admissions in the United States for that period.
      CONCLUSIONS: This network has achieved a large capacity for burn admission and
      currently accounts for 21% of US burn admissions. The network has capacity for
      continued growth and the development of clinical innovations and research.

PMID- 29461288
TI  - Carbon Monoxide and Cyanide Poisoning in the Burned Pregnant Patient: An
      Indication for Hyperbaric Oxygen Therapy.
AB  - Carbon monoxide (CO) is a small molecule poison released as a product of
      incomplete combustion. Carbon monoxide binds hemoglobin, reducing oxygen
      delivery. This effect is exacerbated in the burned pregnant patient by fetal
      hemoglobin that binds CO 2.5- to 3-fold stronger than maternal hemoglobin. With
      no signature clinical symptom, diagnosis depends on patient injury history,
      elevated carboxyhemoglobin levels, and alterations in mental status. The standard
      of care for treatment of CO intoxication is 100% normobaric oxygen, which
      decreases the half-life of CO in the bloodstream from 5 hours to 1 hour.
      Hyperbaric oxygen (HBO2) is a useful adjunct to rapidly reduce the half-life of
      CO to 20 minutes and the incidence of delayed neurologic sequelae. Because of the
      slow disassociation of CO from hemoglobin in the fetus, there is a far stronger
      indication for HBO2 in the burned pregnant patient than in other burn patient
      populations.Cyanide intoxication is often a comorbid disease with CO in
      inhalation injury from an enclosed fire, but may be the predominant toxin. It
      acts synergistically with CO to effectively lower the lethal doses of both
      cyanide and CO. Diagnosis is best made in the presence of high lactate levels,
      carboxyhemoglobin concentrations greater than 10%, injury history of smoke
      inhalation from an enclosed fire, and alterations in consciousness. While
      treatment with hydroxocobalamin is the standard of care and has the effect of
      reducing concomitant CO toxicity, data indicate cyanide may also be displaced by
      HBO2.Carbon monoxide and cyanide poisoning presents potential complications
      impacting care. This review addresses the mechanism of action, presentation,
      diagnosis, and treatment of CO and cyanide poisonings in the burned pregnant
      patient and the use of HBO2 therapy.

PMID- 29461290
TI  - Volume Resuscitation in Patients With High-Voltage Electrical Injuries.
AB  - Volume resuscitation of patients with high-voltage electrical injuries (>1000 V)
      is a more complex challenge than standard burn resuscitation. High voltages
      penetrate deep tissues. These deep injuries are not accounted for in
      resuscitation formulae dependent on percentage of cutaneous burn. Myonecrosis
      occurring from direct electrical injury and secondary compartment syndromes can
      result in rhabdomyolysis, compromising renal function and urine output. Urine
      output is the primary end point, with a goal of 1 mL/kg/h for adult patients with
      high-voltage electrical injuries. As such, secondary resuscitation end points of
      laboratory values, such as lactate, base deficit, hemoglobin, and creatinine, as
      well as hemodynamic monitoring, such as mean arterial pressure and thermodilution
      techniques, can become crucial in guiding optimum administration of resuscitation
      fluids. Mannitol and bicarbonates are available but have limited support in the
      literature. High-voltage electrical injury patients often develop acute kidney
      injury requiring dialysis and have increased risks of chronic kidney disease and
      mortality. Continuous venovenous hemofiltration is a well-supported adjunct to
      clear the myoglobin load that hemodialysis cannot from circulation.

PMID- 29461291
TI  - Fifty Years of Burn Care at Shriners Hospitals for Children, Galveston.
AB  - More than 50 years ago, Shriners Hospitals for Children expanded their
      philanthropy to include care for burned children. In so doing, the effects of
      their work weightily expanded from rehabilitation and quality of life outcomes to
      include survival proper. As the first facility dedicated to the care of burned
      children, originally designated the Shriners Burn Institute, the Galveston
      hospital remains the cornerstone of this endeavor. Shriners maintains charitable
      pediatric hospitals, provide care irrespective of the patient's or the family's
      ability to pay, and promote research. The sole criterion for admission at
      Shriners Hospitals for Children is the determination by a surgeon at a Shriners
      hospital that "the child's trouble may be corrected or improved." This
      philanthropic effort to provide medical care for children is one expression of
      the human commonality recognized by Shriners. In this article, we provide some
      background information on how this hospital came into existence as well as a
      global summary of its interventions toward greater survival and more complete
      rehabilitation of burned children. Based on the findings presented herein, we
      assert that there is less suffering and less loss of life due to childhood burns
      today than in previous years. We attribute much of this improvement to the simple
      voluntary collective decision by Shriners to provide alms for burned children.

PMID- 29461294
TI  - Basic Microvascular Anastomosis Simulation Hub Microsurgery Course: An Innovative
      Competency-Based Approach to Microsurgical Training for Early Year's Plastic
      Surgery Trainees.
AB  - Early year's plastic surgery trainees are faced with a large choice of
      microsurgery courses to select from. In the context of dwindling study budgets
      and busy on-call rotas, the pressure to select a high yield course that delivers
      value for money is of paramount importance.The Basic Microvascular Anastomosis
      Simulation Hub Microsurgery Course is a GBP L600 (US $790) 5-day 40-hour course
      based at Barts and The London School of Medicine and Dentistry increasing in
      popularity among junior trainees to fit this brief.

PMID- 29461293
TI  - Labiaplasty: A 24-Month Experience in 58 Patients: Outcomes and Statistical
      Analysis.
AB  - BACKGROUND: Because there has been a great raise in the interest of this type of
      surgery in our area, we decided to study if there were any differences among our
      patients and also to review our results. OBJECTIVE: The purpose of this study was
      to review our experience with labiaplasty. We assessed surgical complications and
      quality outcomes and compared surgical results according to maternal parity.
      METHODS: We conducted a retrospective chart review of all cases of primary or
      secondary labia minora reduction surgery performed by the same surgeon from
      January 2014 to December 2015. We recorded patient demographics, sexual activity,
      parity, and presurgical and postsurgical quality of life, as well as surgical
      technique and complications. RESULTS: During the study period, we performed 58
      labia minora reduction procedures. The average patient age was 32.16 years. Among
      the patients, 50% were single, 65.52% sexually active, and 62.07% nulliparous. A
      wedge excision was performed in 75.8% of cases. A complication occurred in 12.06%
      of cases, usually owing to underresection. The surgical experience was rated very
      good or excellent by 96.55% of patients. Women with children reported greater
      satisfaction with their surgical outcome on our postoperative questionnaire. We
      identified no statistically significant outcome differences according to surgical
      technique. CONCLUSIONS: Labiaplasty is safe and shows high rates of overall
      satisfaction. Women with children reported greater postoperative satisfaction
      than women who had never given birth.

PMID- 29461292
TI  - Inhalation Injury in the Burned Patient.
AB  - Inhalation injury causes a heterogeneous cascade of insults that increase
      morbidity and mortality among the burn population. Despite major advancements in
      burn care for the past several decades, there remains a significant burden of
      disease attributable to inhalation injury. For this reason, effort has been
      devoted to finding new therapeutic approaches to improve outcomes for patients
      who sustain inhalation injuries.The three major injury classes are the following:
      supraglottic, subglottic, and systemic. Treatment options for these three
      subtypes differ based on the pathophysiologic changes that each one
      elicits.Currently, no consensus exists for diagnosis or grading of the injury,
      and there are large variations in treatment worldwide, ranging from observation
      and conservative management to advanced therapies with nebulization of different
      pharmacologic agents.The main pathophysiologic change after a subglottic
      inhalation injury is an increase in the bronchial blood flow. An induced mucosal
      hyperemia leads to edema, increases mucus secretion and plasma transudation into
      the airways, disables the mucociliary escalator, and inactivates hypoxic
      vasocontriction. Collectively, these insults potentiate airway obstruction with
      casts formed from epithelial debris, fibrin clots, and inspissated mucus,
      resulting in impaired ventilation. Prompt bronchoscopic diagnosis and multimodal
      treatment improve outcomes. Despite the lack of globally accepted standard
      treatments, data exist to support the use of bronchoscopy and suctioning to
      remove debris, nebulized heparin for fibrin casts, nebulized N-acetylcysteine for
      mucus casts, and bronchodilators.Systemic effects of inhalation injury occur both
      indirectly from hypoxia or hypercapnia resulting from loss of pulmonary function
      and systemic effects of proinflammatory cytokines, as well as directly from
      metabolic poisons such as carbon monoxide and cyanide. Both present with
      nonspecific clinical symptoms including cardiovascular collapse. Carbon monoxide
      intoxication should be treated with oxygen and cyanide with
      hydroxocobalamin.Inhalation injury remains a great challenge for clinicians and
      an area of opportunity for scientists. Management of this concomitant injury lags
      behind other aspects of burn care. More clinical research is required to improve
      the outcome of inhalation injury.The goal of this review is to comprehensively
      summarize the diagnoses, treatment options, and current research.

PMID- 29461295
TI  - Labia Majora Augmentation Combined With Minimal Labia Minora Resection: A Safe
      and Global Approach to the External Female Genitalia.
AB  - BACKGROUND: All the labia minora reduction techniques fail to treat the other
      component of the abnormally increased labia minora to majora ratio: the labia
      majora atrophy. The purpose of this study is to describe a technique of female
      genitalia beautification, which combines labia majora augmentation and
      conservative labia minora reduction. METHODS: The hypertrophied labia minora were
      first treated by a conservative inferior wedge excision with a superior flap. The
      conservative excision was done to obtain labia minora that would still protrude
      beyond the labia majora because it will be masked by the augmentation of the
      labia majora. Labia majora augmentation was done by autologous fat
      transplantation. The newly augmented labia majora completely masked the
      conservatively reduced labia minora. RESULTS: Twenty-one patients underwent
      surgery for labia majora augmentation and labia minora reduction. One patient
      (4.7%) had a small separation of the labial edge postoperatively that resolved
      with no additional interventions. There was no flap necrosis or infections. No
      patient reported pain or sexual dysfunction. Seventeen patients (81%) were
      satisfied or very satisfied with their results. CONCLUSIONS: Labia majora
      augmentation combined with a conservative labia minora reduction is an appealing
      procedure because it enhances the global aspect of the female genitalia while
      reducing the labioplasty complications.

PMID- 29461296
TI  - Evidence supporting laparoscopic hernia repair in children.
AB  - PURPOSE OF REVIEW: Pediatric inguinal hernias are a commonly performed surgical
      procedure. Currently, they can be approached via open or laparoscopic surgery. We
      summarize the current evidence for laparoscopic inguinal hernia repairs in
      children. RECENT FINDINGS: Laparoscopic and open inguinal hernia repair in
      children are associated with similar operative times for unilateral hernia, as
      well as similar cosmesis, complication rates and recurrence rates. Bilateral
      hernia repair has been shown to be faster through a laparoscopic approach. The
      laparoscopic approach is associated with decreased pain scores and earlier
      recovery, although only in the initial postoperative period. Laparoscopy allows
      for easy evaluation of the patency of contralateral processus vaginalis, although
      the clinical significance of and need for repair of an identified defect is
      unclear. SUMMARY: Laparoscopic surgery for pediatric inguinal hernias offers some
      advantages over open repair with most outcomes being equal. It should be
      considered a safe alternative to open repair to children and their caregivers.

PMID- 29461297
TI  - Maternal fetal medicine: recent developments and moving forward.

PMID- 29461298
TI  - Adolescent Internet Use, Social Integration, and Depressive Symptoms: Analysis
      from a Longitudinal Cohort Survey.
AB  - OBJECTIVE: To examine the association between adolescent leisure-time Internet
      use and social integration in the school context and how this association affects
      later depressive symptoms among adolescents in Taiwan, using a large nationwide
      cohort study and the latent growth model (LGM) method. METHODS: Data of 3795
      students followed from the year 2001 to 2006 in the Taiwan Education Panel Survey
      were analyzed. Leisure-time Internet use was defined by the hours per week spent
      on (1) online chatting and (2) online games. School social integration and
      depressive symptoms were self-reported. We first used an unconditional LGM to
      estimate the baseline (intercept) and growth (slope) of Internet use. Next,
      another LGM conditioned with school social integration and depression was
      conducted. RESULTS: Approximately 10% of the participants reported engaging in
      online chatting and/or gaming for more than 20 hours per week. Internet use for
      online chatting showed an increase over time. School social integration was
      associated with the baseline amount (coefficient = -0.62, p < 0.001) but not the
      growth of leisure-time Internet use. The trend of Internet use was positively
      related to depressive symptoms (coefficient = 0.31, p < 0.05) at Wave 4.
      CONCLUSION: School social integration was initially associated with decreased
      leisure-time Internet use among adolescents. The growth of Internet use with time
      was not explainable by school social integration but had adverse impacts on
      depression. Reinforcing adolescents' bonding to school may prevent initial
      leisure-time Internet use. When advising on adolescent Internet use, health care
      providers should consider their patients' social networks and mental well-being.

PMID- 29461299
TI  - Reliability of Blotting Techniques to Assess Contact Lens Water Content.
AB  - OBJECTIVES: To determine the reliability of wet and modified dry blotting
      techniques used in the gravimetric method to assess contact lens (CL) water
      content (WC), the accuracy of both techniques in comparison with the nominal WC,
      and also their agreement. METHODS: We evaluated hydrated and dry CL mass values
      and WC using the gravimetric method in 440 daily disposable CLs. Samples assessed
      corresponded to Dailies Total 1, Dailies AquaComfort Plus, 1-Day Acuvue TruEye,
      and Biotrue ONEday. Back vertex power ranged from +3.00 diopters (D) to -6.00 D.
      Within-subject coefficient of variation (CVw) and intraclass correlation
      coefficients were calculated. Bland-Altman analysis was also performed. RESULTS:
      The modified dry blotting technique yielded significantly (P<=0.0001) higher
      hydrated CL mass values. The wet blotting technique provided significantly
      (P<=0.04) better consistency than the modified dry one. Values of CVw for wet and
      modified dry blotting techniques ranged from 1.2% to 2.1% and from 3.7% to 5.4%,
      respectively. As for dry CL mass values, CVw values were not significantly
      different (P>=0.05) between wet (range: 1.1%-1.9%) and dry (range: 1.0%-5.1%)
      blotting techniques, except for Dailies AquaComfort Plus (P=0.03). Bland-Altman
      analysis showed poor agreement between the techniques. The wet blotting technique
      yielded WC values close (around 1%) to nominal ones, in contrast to modified dry
      blotting technique (>=2.5%). CONCLUSIONS: The wet blotting technique is not only
      more reliable than the modified dry one when obtaining hydrated CL mass but also
      provides more accurate nominal WC measurements. Agreement between the techniques
      was poor.

PMID- 29461300
TI  - Intrasession Repeatability and Intersession Reproducibility Measurements Using
      VX120 Multidiagnostic Unit.
AB  - OBJECTIVE: The VX120 multidiagnostic unit is a multidiagnostic instrument that
      combines several functions: autorefraction, keratometry, corneal topography,
      aberrometry, pachymetry, and noncontact tonometry. The purpose of this study was
      to determine the intrasession repeatability and the intersession reproducibility
      of all parameters measured by the VX120 multidiagnostic unit in a sample of
      normal healthy eyes. METHODS: Three repeated measurements in the right eye of the
      volunteers were taken with VX120. Repeatability of the sphere, cylinder, axis,
      anterior corneal powers (K flat and K steep, 3-mm pupil), high- and low-order
      aberration root mean square (HOA-RMS and LOA-RMS, 3-mm pupil), eccentricity,
      white-to-white (WTW), anterior chamber depth (ACD), and central corneal thickness
      (CCT) (2-mm central) was analyzed. Within-subject SD (Sw), precision,
      repeatability, coefficient of variation (CV), and the intraclass correlation
      coefficient (ICC) were calculated. RESULTS: The CV was low for K flat and K
      steep, WTW, ACD, and CCT with a range from 0.34% to 1.16%. The CV was higher for
      sphere, cylinder, HOA-RMS, and LOA-RMS and eccentricity with a range among 6.92%
      to 54.24%. The ICC showed high values in all parameters except in HOA-RMS (0.720
      0.776) and eccentricity (0.889) in first session with moderate agreement.
      Comparing the intrasession repeatability of first and second session,
      statistically significant differences (P<0.01) were found between both sessions
      just to the CV for all parameters (except cylinder values) measured with VX120.
      However, nonstatistically significant differences (P>0.13) were found for Sw,
      precision, and repeatability values. CONCLUSIONS: The VX120 multidiagnostic unit
      provides repeatable measurements in anterior corneal power (K flat and K steep),
      WTW, ACD, and CCT. However sphere, cylinder, HOA-RMS, LOA-RMS, and eccentricity
      showed worse repeatability. Intersession reproducibility showed good results with
      little differences between sessions in healthy subjects.

PMID- 29461302
TI  - Does initial use of benzodiazepines delay an adequate pharmacological treatment?
      A multicentre analysis in patients with psychotic and affective disorders.
AB  - It is established that delayed effective pharmacotherapy plays a significant role
      in the overall burden of psychiatric disorders, which are often treated with
      symptomatic drugs, that is benzodiazepines (BZDs), in relation to their rapid
      onset of action and safety, despite long-term side effects. We aimed to assess
      the influence of initial treatment with BZDs on the duration of untreated illness
      (DUI) and whether specific sociodemographic and clinical factors could influence
      the choice of BZDs as first treatment in 545 patients affected by schizophrenia,
      mood and anxiety spectrum disorders. Statistical analyses (one-way analysis of
      variance and chi) were carried out to compare patients who used BZDs as first
      treatment (BZD w/) and those who did not (BZD w/o). The overall DUI, irrespective
      of diagnosis, resulted in significantly longer in BZD w/ versus w/o patients, who
      also experienced more frequently anxious/depressive symptoms at onset.
      Furthermore, BZD w/ patients more frequently autonomously decided to look for
      treatment (mainly refering to psychologists or general practitioners) and
      experimented more frequently phobias, than BZD w/o ones. The present findings
      suggest that initial BZDs treatment may prolong the overall DUI, although their
      prescription seems to be influenced by specific sociodemographic and clinical
      factors. Further studies are needed to confirm the present findings.

PMID- 29461301
TI  - Davydov Procedure for Augmenting Vaginal Length in a Postsurgical Male-to-Female
      Transgender Patient.
AB  - Male-to-female gender reassignment surgery may lead to unsatisfactory vaginal
      length. No standard approaches are established to treat these patients. We
      present a case of vaginoplasty using the laparoscopic Davydov technique performed
      on a male-to-female transgender patient. Our case provides a novel approach to
      treating this rare condition and introduces Davydov procedure as a potentially
      effective and safe treatment. Preoperative endovaginal and endoanal 3-dimensional
      ultrasounds and a pelvic magnetic resonance imaging of the case are presented to
      provide details of this patient's unique anatomy.

PMID- 29461304
TI  - A Systematic Review of Culturally Specific Interventions to Increase Physical
      Activity for Older Asian Americans.
AB  - BACKGROUND: Physical activity (PA) is a significant modifiable risk factor for
      cardiovascular disease. For older adults, engaging in PA is shown to improve
      cardiac status, reduce cognitive, and functional decline, and improve overall
      quality of life. However, only 17% of Asian American adults meet the 2008 federal
      recommended guidelines for aerobic and muscle strengthening activity; and there
      is a paucity of data reporting on older Asian Americans - a rapidly growing,
      underserved group. While data pertaining to Asian Americans is frequently
      reported at the aggregate level, this masks differences (eg, language, culture,
      income) among Asian ethnic subgroups that may impact health behaviors. The
      purpose of this review was to identify intervention, and cultural adaptation
      strategies in studies promoting PA for older Asian Americans. METHODS: A
      comprehensive literature search was performed to identify interventions published
      between 1996-2016 focused on improving PA among older Asian Americans (> 60 years
      old). Data were abstracted to examine intervention study designs, cultural
      adaptation strategies, theoretical frameworks, and physical activity measures.
      RESULTS: Nine studies met the review's inclusion criteria. Community-based
      recruitment approaches were widely used, and all studies employed cultural
      adaptation to varying degrees. Most studies reported improvements in PA outcomes,
      focused on Chinese Americans, and relied on self-reports of PA, while few aimed
      to increase PA using a multi-component approach. CONCLUSIONS: Future studies
      would benefit from larger sample sizes, a wider representation of Asian ethnic
      subgroups, and concentrated efforts to implement deep level adaptations that may
      increase the salience and sustainability of these interventions.

PMID- 29461303
TI  - Agreement Between Automated and Human Measurements of Heart Rate in Patients With
      Atrial Fibrillation.
AB  - BACKGROUND: The accuracy of heart rate (HR) measurement by automated blood
      pressure monitors in patients with atrial fibrillation (AF) remains unclear. The
      authors investigate the agreement between HR measurements by 2 automated devices
      and human counting in patients with AF. METHODS: In 47 patients with persistent
      AF, HR was recorded using 2 automated blood pressure monitors: Omron M5-I and
      Microlife BPA100 Plus. Human counting of HR by a stethoscope was used as the
      reference. For each method, 3 readings were made and the mean was calculated for
      comparison. In addition to Wilcoxon signed rank test, the correlation between HR
      measurements by automated devices and human counting was determined using
      Spearman's rank correlation coefficient (r), and the agreement between HR
      measurements by both devices and human counting was validated by the Bland-Altman
      plot and intraclass correlation coefficient (ICC). RESULTS: Overall, we found no
      significant difference in HR measurements between devices and human counting
      (Omron vs human counting, 81.1 +/- 11.1 vs 80.2 +/- 10.8 beats per minute [bpm];
      P = .21, r = 0.911; ICC, 0.954; Microlife vs human counting, 81.3 +/- 10.8 vs
      80.2 +/- 10.8 bpm; P = .22, r = 0.842; ICC, 0.912). However, in patients with HR
      greater than 80 bpm, the HR measured by the Microlife device was significantly
      higher than that measured by human counting (91.1 +/- 5.2 vs 87.1 +/- 8.6 bpm, P
      = .034). CONCLUSION: There was a high agreement between HR measurements by 2
      automated devices and human counting, but the Microlife device may overestimate
      HR in AF patients with HR greater than 80 bpm.

PMID- 29461306
TI  - Survivorship of Hemiarthroplasty With Concentric Glenoid Reaming for Glenohumeral
      Arthritis in Young, Active Patients With a Biconcave Glenoid.

PMID- 29461305
TI  - Transcatheter Aortic Valve Replacement as a Bridge to Left Ventricular Assist
      Device Implantation.
AB  - We describe a case of the pre-emptive use of transcatheter aortic valve
      replacement in a patient with end-stage ischemic cardiomyopathy and native aortic
      stenosis/aortic insufficiency as a bridge to left ventricular assist device
      implantation. The use of this strategy can not only medically optimize patients
      before left ventricular assist device implantation but also provide a minimally
      invasive bridge to left ventricular assist device support, avoiding concomitant
      surgical aortic valve replacement or closure.

PMID- 29461307
TI  - Are graft-versus-host-disease patients missing out on the vital occupational
      therapy services? a systematic review.
AB  - The aim of this review is to show the importance of occupational therapy/hand
      therapy for chronic graft-versus-host-disease (GVHD) patients and to outline the
      current state of the literature. GVHD of the hand can cause functional loss,
      reduced activities of daily life, poor social interaction, and loss of income
      because of limitations in work. Hand therapy, which is a specialty practised by
      both occupational therapists and physical therapists, has been proven to be an
      effective approach for hand-related musculoskeletal disorders; however, the
      literature search suggests that it is an underutilized specialty around the
      world. An electronic search was performed from 1997 to 2017 using OneFile (GALE),
      Medline/PubMed (NLM), Scopus (Elsevier), Science Citation Index Expanded (Web of
      Science), ProQuest Central (New), ProQuest Hospital Collection, Health Reference
      Center Academic (Gale), Health Research Premium Collection, Science Direct
      Journals (Elsevier), ProQuest Health & Medical Complete, Medical Database, Wiley
      Online Library, and SciTech Premium Collection for the period from 1994 to April
      2017. Only randomized-controlled trials involving occupational therapy or hand
      therapy in patients with chronic hand GVHD were included in the final analysis.
      The search was limited to articles in English. Two reviewers independently
      assessed the methodological quality and extracted the data. The JADAD scoring
      method was used to score the articles. After the duplicates were excluded, 5466
      articles were identified by the electronic database search for screening, out of
      which 5465 articles were excluded after reviewing. One article was further
      excluded on obtaining the full text as it was a case study. Hand therapy
      specialty, although a vital part of the recovery process for the patients with
      hand GVHD, is an underutilized specialty and well-designed trials are urgently
      needed for musculoskeletal hand GVHD, especially for focused hand therapy
      interventions.

PMID- 29461308
TI  - Interprofessional Communities of Practice in Continuing Medical Education for
      Promoting and Sustaining Practice Change: A Prospective Cohort Study.
AB  - INTRODUCTION: Standard knowledge delivery formats for CME may have limited impact
      on long-term practice change. A community of practice (CoP) is one tool that may
      enhance competencies and support practice change. This study explores the utility
      of an interprofessional CoP as an adjunct to a CME program in tobacco addiction
      treatment (Training Enhancement in Applied Counselling and Health [TEACH]
      Project) to promote and sustain practice change. METHODS: A prospective cohort
      design was utilized to examine the long-term impact of the TEACH CoP on practice
      change. An online survey was administered to TEACH-trained practitioners to
      assess perceived feasibility, importance, and confidence related to course
      competencies, involvement in TEACH CoP activities, engagement in knowledge
      transfer (KT), and implementation of new programming. Chi-square tests were used
      to detect differences in KT and program development associated with CoP
      participation. Course competency scores from immediate postcourse surveys and
      long-term follow-up surveys were compared. RESULTS: No significant differences in
      participant characteristics were found between those who did (n = 300) and did
      not (n = 122) participate in the TEACH CoP. Mean self-perceived competency scores
      were greater immediately after course than at long-term follow-up; however, self
      ratings of competency in pharmacological interventions and motivational
      interviewing were higher at follow-up. TEACH CoP participation was associated
      with significantly greater engagement in KT and implementation of new programming
      after training. DISCUSSION: The findings from this evaluation suggest the value
      of interprofessional CoPs offered posttraining as a mechanism to enhance
      practice. CME providers should consider offering CoPs as a component of training
      programs to promote and sustain practice change.

PMID- 29461309
TI  - Foreword.

PMID- 29461311
TI  - Looking For Food: Food Access, Food Insecurity, and the Food Environment in Rural
      Mississippi.
AB  - Mississippi has the highest food insecurity rate in the nation, and while the
      overall pattern of food insecurity has declined in the United States, for
      Mississippians it has plateaued, remaining significantly higher than prerecession
      rates. In addition, the food environment of the state is characterized by low
      healthy food access, high persistent poverty, and a primarily rural landscape.
      This translational research seeks to bridge thinking on agriculture policy,
      nutrition, food access/food insecurity in seeking to understand the paradox
      between obesity and poverty in rural Mississippi. Examining food system
      opportunities as potential solutions to food access and healthy outcomes is
      explored.

PMID- 29461310
TI  - Examining the Impact of Structural Racism on Food Insecurity: Implications for
      Addressing Racial/Ethnic Disparities.
AB  - Food insecurity is defined as "a household-level economic and social condition of
      limited or uncertain access to adequate food." While, levels of food insecurity
      in the United States have fluctuated over the past 20 years; disparities in food
      insecurity rates between people of color and whites have continued to persist.
      There is growing recognition that discrimination and structural racism are key
      contributors to disparities in health behaviors and outcomes. Although several
      promising practices to reduce food insecurity have emerged, approaches that
      address structural racism and discrimination may have important implications for
      alleviating racial/ethnic disparities in food insecurity and promoting health
      equity overall.

PMID- 29461312
TI  - A Theoretically-Grounded Investigation of Perceptions About Healthy Eating and
      mHealth Support Among African American Men and Women in New Orleans, Louisiana.
AB  - There has been a surge in diet-related mobile health (mHealth) interventions.
      However, diet-related mHealth research targeted toward racial/ethnic populations
      has been relatively limited. Focus groups with African American men and women
      from New Orleans, Louisiana, were conducted to (1) describe perceptions about
      healthy eating, (2) determine the acceptability of mHealth interventions, and (3)
      identify preferred mHealth intervention features. Descriptive statistics and
      thematic content analyses were performed. Qualitative data were organized within
      the context of the Theory of Planned Behavior and Social Cognitive Theory's
      theoretical components. Results may inform the development of mHealth research to
      improve eating behaviors among the target population.

PMID- 29461313
TI  - Sex, Race, Food Security, and Sugar Consumption Change Efficacy Among Low-Income
      Parents in an Urban Primary Care Setting.
AB  - The purpose of this study was to examine relationships between food security and
      parents' self-efficacy to reduce consumption of sugar-sweetened beverages and
      sugary snacks in a sample of parents in waiting rooms in community-based primary
      care clinics in West Tennessee. Results from logistic regression models
      underscore the need for nuanced analysis, as the results from the pooled
      regression models differ from those stratified by food security status. Self
      efficacy is an important factor for behavior change, and our study highlights the
      need for additional research examining how social, psychological, and behavioral
      factors have implications for behavior change self-efficacy.

PMID- 29461315
TI  - Perioperative Cardiac Arrest: Focus on Anaphylaxis.

PMID- 29461316
TI  - Perioperative Cardiac Arrest: Focus on Local Anesthetic Systemic Toxicity (LAST).

PMID- 29461314
TI  - Social and Demographic Predictors of Nutritional Risk: Cross-sectional Analyses
      From the UAB Study of Aging II.
AB  - Social factors may disparately affect access to food and nutritional risk among
      older adults by race and gender. This study assesses these associations using the
      Mini Nutritional Assessment among 414 community-dwelling persons 75+ years of age
      in Alabama. Descriptive analyses on the full sample and by African American men,
      African American women, white men, and white women showed that mean scores for
      the full Mini Nutritional Assessment differed by groups, with African American
      men and African American women having the highest nutritional risk. Multivariable
      analyses indicated that social factors affect nutritional risk differently by
      race and gender. Nutritional risk interventions are warranted for older adults.

PMID- 29461317
TI  - Perioperative Cardiac Arrest: Focus on Malignant Hyperthermia (MH).

PMID- 29461318
TI  - Post-Cardiac Arrest Management: Time to Cool It on Cooling?

PMID- 29461319
TI  - Meta-analysis, Medical Reversal, and Settled Science.

PMID- 29461320
TI  - Motor Evoked Potential Monitoring During Thoracoabdominal Aortic Surgery: Useful
      or Not?

PMID- 29461321
TI  - The Night Shift Nightmare.

PMID- 29461322
TI  - Anesthesia Advanced Cardiac Life Support: A Guideline Validated?

PMID- 29461323
TI  - Hyperglycemia and Elevated Lactate in Trauma: Where Do We Go From Here?

PMID- 29461324
TI  - Between a ROCK and an IR Place.

PMID- 29461325
TI  - To Ask or Not to Ask: The Ethics of Informed Consent for Transesophageal
      Echocardiography Education.

PMID- 29461326
TI  - Consensus Statement on Pregnant Women Receiving Thromboprophylaxis: An Essential
      Tool to Guide Our Management.

PMID- 29461328
TI  - The challenges of timely and safe HIV disclosure among perinatally HIV-infected
      adolescents in sub-Saharan Africa.
AB  - PURPOSE OF REVIEW: Improved access to antiretroviral therapy has resulted in an
      emerging population of adolescents living with HIV (ALHIV) mainly in sub-Saharan
      Africa. Full disclosure of an HIV diagnosis includes naming HIV/AIDS and is an
      important step in coping with HIV. We reviewed the recent trends in the rates of
      children/adolescents who have been informed of their HIV infection according to
      age groups, the barriers and the evaluated interventions aimed at improving the
      HIV disclosure process to ALHIV in sub-Saharan Africa. RECENT FINDINGS:
      Literature shows that HIV disclosure remains challenging in sub-Saharan Africa.
      Although full HIV disclosure rates have increased recently, this is still
      insufficient and occurs at a late age (median 13 years). Individual disclosure is
      the main practice but group sessions involving adolescent peers also exist. The
      practice of the disclosure is often complex, because of multiple barriers related
      to caregivers (fear of the parents of the breaking of the family secrecy,
      feelings of guilt) and to healthcare workers (lack of training, excess workload).
      SUMMARY: The development and evaluation of research interventions adapted to
      sociocultural contexts to support timely and safe HIV disclosure to ALHIV is
      urgently needed to reach the 90-90-90 UNAIDS targets.

PMID- 29461330
TI  - Sexual and reproductive health in HIV-positive adolescents.
AB  - PURPOSE OF REVIEW: This review aims to summarize data in the last 18 months on
      the sexual and reproductive health of perinatally and horizontally infected
      adolescents and young people living with HIV (age 13-25 years) and to highlight
      some key issues faced by this group of adolescents as they reach puberty and
      sexual debut. RECENT FINDINGS: Adolescents and young people living with HIV are a
      growing cohort worldwide and a significant proportion engage in high-risk sexual
      activity, pose risk of onward HIV transmission, yet have poor access to sexual
      and reproductive health (SRH) services and lack the knowledge and support to
      advocate for their needs. SUMMARY: Providing adolescents living with HIV with
      access to SRH services is essential. Integrated HIV and SRH services and peer
      support models work well. HIV healthcare providers should educate all young
      people around disclosure, treatment as prevention and adherence, options for
      preexposure and postexposure prophylaxis and contraception, and support them to
      advocate for their own sexual health.

PMID- 29461329
TI  - Cancer in adolescents and young adults living with HIV.
AB  - PURPOSE OF REVIEW: Adults living with HIV have an increased risk of malignancy
      yet there is little data for adolescents and young adults. We reviewed recently
      published cancer epidemiology, treatment, and outcome data for adolescents and
      young adults living with HIV (AYALHIV) aged 10 to less than 25 years between 2016
      and 2017. RECENT FINDINGS: AYALHIV are at increased risk of developing cancer
      compared to their uninfected peers. Kaposi sarcoma and non-Hodgkin lymphoma occur
      most frequently with variation by geographical region. Increased cancer risk is
      associated with HIV-related immunosuppression and coinfection with oncogenic
      viruses. Published data, particularly on posttreatment outcomes, remain limited
      and analyses are hampered by lack of data disaggregation by age and route of HIV
      transmission. SUMMARY: Although data are sparse, the increased cancer risk for
      AYALHIV is the cause for concern and must be modified by improving global access
      and uptake of antiretroviral therapy, human papilloma virus (HPV) and hepatitis B
      virus (HBV) vaccination, screening for hepatitis B and C infection, and optimized
      cancer screening programs. Education aimed at reducing traditional modifiable
      cancer risk factors should be embedded within multidisciplinary services for
      AYALHIV.

PMID- 29461331
TI  - The Effect of Electroconvulsive Therapy on Hypoperfusion in Psychotic Bipolar
      Depression: A Case Study.
AB  - The pharmacological treatment of bipolar depression has low response rates.
      Twenty percent to 30% of patients have an insufficient response to medication.
      The guidelines suggest that electroconvulsive therapy (ECT) is the next step. The
      aim of this case study is to evaluate the effect of ECT on the perfusion of the
      brain in bipolar depression, while monitoring effects on mood and cognition. We
      present a case study of 56-year-old female patient who suffered from a psychotic
      depression and cognitive impairment. Before ECT, she took several antidepressants
      and atypical antipsychotics, but there was no improvement in her symptoms. By
      using single-photon emission computed tomography, we obtained the status of the
      regional cerebral blood flow and found a decreased perfusion in the anterior part
      of the left temporal lobe, the posterior part of the right temporal lobe, and in
      the left gyrus frontalis inferior. This is consistent with previous findings.
      Electroconvulsive therapy resulted in a resolution of the patient's depression
      and an improvement in her neurocognitive performance. Markedly, this was only in
      visual learning and working memory, domains in which the patient was already
      relatively stronger pre-ECT treatment. A new single-photon emission computed
      tomography, 4 weeks after the last ECT course, showed normalization of the
      regional cerebral blood flow.

PMID- 29461332
TI  - Improvements in Health-Related Quality of Life With Electroconvulsive Therapy: A
      Meta-analysis.
AB  - INTRODUCTION: Although the antidepressant efficacy of ECT is well documented,
      patient-reported outcomes after this treatment are less well characterized. The
      aims of the current meta-analysis are to quantify the impact of an acute course
      of ECT on health-related quality of life (HRQoL) and to identify related
      moderators, specifically post-ECT depressive symptom remission and patient age.
      METHODS: We searched PubMed, PsycINFO, and Web of Science databases for
      randomized and nonrandomized studies that report on changes in HRQoL measures
      after an acute course of ECT. Only studies that used the Medical Outcomes Study
      Short Form 36 (SF-36) instrument were included. A random effects model using the
      Hedges' g effect size was used in calculating the pre-post ECT outcomes on all 8
      SF-36 subscales and the SF-36 total scores including the physical and mental
      composite scores. Subgroup analyses were conducted using remission status and age
      as moderators. RESULTS: Four studies contributed to this analysis. Significant
      improvements across all subscales of the SF-36 were observed. Large and very
      large effect sizes were present for both the SF-36 physical component score (PCS)
      and mental health component score (MCS), with the change in MCS being
      statistically superior to the PCS (MCS, Hedges' g = 1.28; 95% confidence
      interval, 1.15-1.42; PCS, Hedges' g = 0.97; 95% confidence interval, 0.86-1.07).
      Medium, large, and very large effect sizes were observed for SF-36 subscales
      scores. Post-ECT depression remission status was related to HRQoL improvement,
      with statistically significant differences present between remitters and
      nonremitters for PCS, MCS, and most SF-36 subscale scores. No significant
      differences were observed in improvement in HRQoL with ECT based on patient age.
      CONCLUSIONS: An acute course of ECT for depressive symptoms produces medium to
      very large effect size improvements in HRQoL across multiple components and
      subscales measured by the SF-36. The magnitude of the effects reported by ECT
      patients is greater than those that have been reported in other open-label
      studies of brain stimulation techniques. This study confirms that ECT plays a
      vital role in the treatment of the most severely ill patients with depressive
      disorders.

PMID- 29461333
TI  - Metabolic Syndrome Among Asian Indians in the United States.
AB  - INTRODUCTION: Metabolic syndrome (MetS), a clustering of cardiometabolic risk
      factors of type 2 diabetes and cardiovascular disease, disproportionately affects
      Asian Indians (AIs). We examined prevalence of MetS using 3 ethnicity-specific
      MetS criteria among immigrant AIs in the United States. We also examined
      associations between MetS and health promotion behaviors. OBJECTIVE: To present
      MetS prevalence estimates by the 3 ethnicity-specific criteria and investigate
      differences in health promotion behaviors among AIs with and without MetS to
      highlight the critical need for lifestyle modification strategies for this
      population. DESIGN: We analyzed data from a national cross-sectional study of
      1037 AIs in the United States (2004-2006). We used the consensus criteria,
      International Diabetes Federation criteria, and modified criteria to estimate
      MetS prevalence. The Health Promotion Lifestyle Profile II scale measured health
      promotion behaviors. Bioclinical data (fasting blood glucose, triglyceride
      levels) were collected. Directed acyclic graphs and Likelihood Ratio Test
      assisted with model selection. Multiple imputation inference incorporated
      uncertainty due to missing data and made use of all available data. Adjusted
      multivariable logistic regression analysis tested for associations. RESULTS: Out
      of all participants, 40.3% met the consensus criteria, 34.8% met the
      International Diabetes Federation criteria, and 52.5% met the modified criteria.
      We found no statistically significant associations between engagement in health
      promotion measures and the prevalence of MetS and its criteria. CONCLUSION: Our
      study confirmed the high prevalence of MetS in the immigrant AI population in the
      United States. Our results showed that AIs with MetS did not exhibit an increased
      level of engagement in health promotion behaviors. We recommend continued
      refining of criteria for diagnosis and culturally suitable, age-appropriate
      strategies to increase engagement in healthier lifestyles among this high-risk
      population.

PMID- 29461334
TI  - A Patient Safety Toolkit for Family Practices.
AB  - OBJECTIVE: Major gaps remain in our understanding of primary care patient safety.
      We describe a toolkit for measuring patient safety in family practices. METHODS:
      Six tools were used in 46 practices. These tools were as follows: National Health
      Service Education for Scotland Trigger Tool, National Health Service Education
      for Scotland Medicines Reconciliation Tool, Primary Care Safequest, Prescribing
      Safety Indicators, Patient Reported Experiences and Outcomes of Safety in Primary
      Care, and Concise Safe Systems Checklist. RESULTS: Primary Care Safequest showed
      that most practices had a well-developed safety climate. However, the trigger
      tool revealed that a quarter of events identified were associated with moderate
      or substantial harm, with a third originating in primary care and avoidable.
      Although medicines reconciliation was undertaken within 2 days in more than 70%
      of cases, necessary discussions with a patient/carer did not always occur. The
      prescribing safety indicators identified 1435 instances of potentially hazardous
      prescribing or lack of recommended monitoring (from 92,649 patients). The Concise
      Safe Systems Checklist found that 25% of staff thought that their practice
      provided inadequate follow-up for vulnerable patients discharged from hospital
      and inadequate monitoring of noncollection of prescriptions. Most patients had a
      positive perception of the safety of their practice although 45% identified at
      least one safety problem in the past year. CONCLUSIONS: Patient safety is complex
      and multidimensional. The Patient Safety Toolkit is easy to use and hosted on a
      single platform with a collection of tools generating practical and actionable
      information. It enables family practices to identify safety deficits that they
      can review and change procedures to improve their patient safety across a key
      sets of patient safety issues.This is an open-access article distributed under
      the terms of the Creative Commons Attribution-Non Commercial-No Derivatives
      License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work
      provided it is properly cited. The work cannot be changed in any way or used
      commercially without permission from the journal.

PMID- 29461335
TI  - 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-beta-D-pyranoside, an analog of
      salidroside, contributes to neuroprotection in cerebral ischemic injury in vitro
      and in vivo.
AB  - 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxyb-D-pyranoside (code-named SalA-4g),
      an analog of salidroside, has potent neuroprotective effects. In this study, the
      pharmacological properties of SalA-4g were evaluated in primary cortical neurons
      exposed to oxygen and glucose deprivation and in a rat model of transient middle
      cerebral artery occlusion. The results of pharmacokinetic and brain distribution
      studies indicated that SalA-4g could pass through the blood-brain barrier with a
      relatively short elimination time. 3-[4,5-Dimethyl-2-thiazolyl]-2,5-diphenyl
      tetrazolium bromide assay, terminal deoxynucleotidyl transferase dUTP nick-end
      labeling, and Annexin V staining collectively showed that SalA-4g inhibited
      neuronal viability loss and apoptosis in a concentration-dependent manner in an
      oxygen and glucose deprivation model. Fluorine-18-fluorodeoxyglucose PET/CT
      imaging indicated that SalA-4g improved metabolic recovery in the ischemic
      hemisphere in a rat middle cerebral artery occlusion model. Our findings provide
      further evidence of the potential therapeutic applications of SalA-4g for the
      treatment of cerebral ischemic injury.

PMID- 29461336
TI  - Sex differences in antinociceptive response to Delta-9-tetrahydrocannabinol and
      CP 55,940 in the mouse formalin test.
AB  - Cannabinoids have shown promise for the treatment of intractable pain states and
      may represent an alternative pharmacotherapy for pain management. A growing body
      of clinical evidence suggests a role for sex in pain perception and in
      cannabinoid response. We examined cannabinoid sensitivity and tolerance in male
      and female mice expressing a desensitization-resistant form (S426A/S430A) of the
      cannabinoid type 1 receptor (CB1R). Mice were assessed for acute and inflammatory
      nociceptive behaviors in the formalin test following pretreatment with either
      vehicle or mixed CB1R/CB2R agonists, Delta-9-tetrahydrocannabinol ([INCREMENT]
      THC) (1-6 mg/kg) or CP 55,940 (0.06-0.2 mg/kg). Tolerance to the effects of 6
      mg/kg [INCREMENT]-THC or 0.1 mg/kg CP 55,940 was examined by the formalin test
      following chronic daily dosing. Female mice showed decreased sensitivity to the
      effects of [INCREMENT]-THC and CP 55,940 compared with male mice. The S426A/S430A
      mutation increased the attenuation of nociceptive behaviors for both agonists in
      both sexes. Female mice displayed delayed tolerance to [INCREMENT]-THC compared
      with male mice, whereas the S426A/S430A mutation conferred a delay in tolerance
      to [INCREMENT]-THC in both sexes. Male S426A/S430A mutant mice also display
      resistance to tolerance to CP 55,940 compared with wild-type controls. This study
      demonstrates sex and genotype differences in response for two different
      cannabinoid agonists. The results underscore the importance of including both
      male and female mice in preclinical studies of pain and cannabinoid pharmacology.

PMID- 29461337
TI  - Habitual action video game players display increased cortical thickness in the
      dorsal anterior cingulate cortex.
AB  - Action video game players (aVGPs) display increased performance in attention
      based tasks and enhanced procedural motor learning. In parallel, the anterior
      cingulate cortex (ACC) is centrally implicated in specific types of reward-based
      learning and attentional control, the execution or inhibition of motor commands,
      and error detection. These processes are hypothesized to support aVGP in-game
      performance and enhanced learning though in-game feedback. We, therefore, tested
      the hypothesis that habitual aVGPs would display increased cortical thickness
      compared with nonvideo game players (nonVGPs). Results showed that the aVGP group
      (n=17) displayed significantly higher levels of cortical thickness specifically
      in the dorsal ACC compared with the nonVGP group (n=16). Results are discussed in
      the context of previous findings examining video game experience,
      attention/performance, and responses to affective components such as pain and
      fear.

PMID- 29461338
TI  - Reading Among Nursing and Nonnursing Students in Undergraduate Education.
AB  - Promoting reading compliance is a common concern in undergraduate education. This
      study described the reading behaviors, preferences, and perceptions of 519
      undergraduate nursing and nonnursing students concerning course-related reading
      assignments. Mean time completing assigned course readings for nursing students
      was 6.63 hours per week; it was similar for other majors (6.73 hours). Nonnursing
      majors read a greater percentage of their assigned readings than nursing students
      (t = -6.59, P < .01). Implications highlight strategies faculty can implement to
      facilitate student reading.

PMID- 29461339
TI  - Neoadjuvant Bleomycin, Etoposide, and Cisplatin (BEP) Chemotherapy in the
      Treatment of Extensively Advanced Yolk Sac Tumors: A Single Center Experience.
AB  - OBJECTIVE: This study aimed to investigate the role of neoadjuvant bleomycin,
      etoposide, and cisplatin (BEP) regimen in patients with extensively advanced yolk
      sac tumors (YSTs). METHODS: Between July 1982 and December 2015, a total of 58
      patients with YST were initially treated at our institution, among which 18 were
      evaluated to be inoperable and received neoadjuvant BEP regimen. They were either
      too debilitated by the disease [Eastern Cooperative Oncology Group Performance
      Status Scale (ECOG ps) >=2] to undergo a major surgery or were with too
      extensively disseminated lesions to be optimally debulked. This cohort of
      patients was retrospectively reviewed. RESULTS: One or 2 cycles of BEP regimen
      were prescribed to the majority of patients preoperatively. At the completion of
      neoadjuvant chemotherapy, 17 of them had ECOG ps of 1 or less. Seventeen (94.4%)
      exhibited clinical partial tumor regression, and 1 (5.6%) had clinical stable
      disease. Pathological complete tumor regression was observed in 2 (11.1%)
      patients, whereas the remaining 16 (88.9%) had nearly complete pathological
      regression. Seventeen patients were cytoreduced to no macroscopic residual
      disease; the remaining 1 was cytoreduced to macroscopic residual disease of 2 cm
      or less. No major surgical complications occurred. After a median follow-up of
      83.5 months, 17 patients were free of recurrence. Five-year disease-free survival
      and overall survival were both 94.4%. Fertility-sparing surgery was carried out
      in all the 17 patients with the desire to preserve their fertility, and 5 infants
      were delivered in 6 patients who attempted conception. CONCLUSIONS: One or 2
      cycles of neoadjuvant BEP regimen followed by cytoreductive surgery offer a
      chance for cure in extensively advanced patients with YSTs and help pave the way
      for fertility-sparing surgery.

PMID- 29461340
TI  - Attitudes About Cognitive Screening: A Survey of Home Care Physical Therapists.
AB  - BACKGROUND AND PURPOSE: Home care physical therapists (PTs) are inconsistent
      regarding cognitive screening, possibly because screening tools were
      traditionally considered the domain of other home care disciplines, or because
      therapists perceive their dementia training to be inadequate. A cross sectional
      study was designed to survey home care therapists' attitudes and beliefs about
      the management of persons with dementia and to find out whether any specific
      cognitive tools or measures are currently used. METHODS: A 5-point Likert-type
      survey was administered to home care PTs via an online survey. Three state home
      care associations and individual home care agencies agreed to share the survey
      link. The survey was also made available to American Physical Therapy Association
      members through the Home Health and Geriatric Section listservs. RESULTS AND
      DISCUSSION: Two hundred fifty-one PTs opened the survey and 233 completed the
      survey. Respondents included 180 females and 53 males. Seventy-four had a
      bachelor's degree (BS), 53 held a master's degree (MS), 104 had achieved a doctor
      of physical therapy (DPT) or doctor of philosophy (PhD) degree, and 2 did not
      provide this information. Significant differences were found between those with
      the highest doctoral degrees and those with master's or bachelor's degrees (P =
      .01) regarding whether they were qualified to screen (strongly agree, agree) for
      cognitive deficits. Therapists with the highest degrees also attended continuing
      education for dementia training more than those with less formal education (P =
      .042.) Gender differences were found in 2 questions regarding positive outcomes
      (P = .010 and .42); for both questions, males were more likely to believe that
      dementia has a negative impact. Eighty-seven percent indicated that PTs are
      qualified (strongly agree, agree), but only 53% said that they possess the
      necessary skills (strongly agree, agree) to perform cognitive screens. Specialty
      certification revealed significant differences in several of the questions. No
      significance was found for any question regarding years of practice or years in
      home care. The Mini-Mental State Examination and the Clock Drawing Test were most
      frequently cited among PTs who conduct cognitive screening. CONCLUSIONS: Physical
      therapists recognize that they are qualified to perform cognitive screening but
      may need additional training to utilize cognitive findings to enhance
      interventions and outcomes in home care. More research is needed to determine
      which screens are most relevant for therapist use and to examine the effect of
      cognitive screening on therapy outcomes.

PMID- 29461341
TI  - Influence of the Initial Sagittal Lumbar Alignment on Clinical and Radiological
      Outcomes of Single-Level Lumbar Total Disc Replacements at a Minimum 2-Year
      Follow-up.
AB  - STUDY DESIGN: Retrospective cohort study OBJECTIVE.: To analyze the clinical and
      radiographic outcomes of patients undergoing a one-level lumbar total disc
      replacement (TDR), according to the initial sagittal alignment of the spine.
      SUMMARY OF BACKGROUND DATA: No authors have highlighted correlation between the
      initial spinopelvic parameters and the postoperative outcome after a one-level
      TDR. METHODS: Seventy-eight patients were included: 14 TDR at L4-L5 and 64 TDR at
      L5-S1 level. Clinical assessment was performed on leg pain and axial back pain
      Visual Analog Scale (VAS), Oswestry Disability Index, and Short Form-36 Health
      Survey. Radiographic assessment included full spine standing anteroposterior and
      lateral films. Data were compared according to the initial lumbar sagittal
      alignment described by Roussouly. RESULTS: Forty-five female patients and 33 male
      patients with a mean age of 41.7 years (95% confidence interval [40.3-43.1]) were
      included. The mean follow-up was 46.4 months (95% [40.6-51.6]). Two patients were
      considered as Roussouly type 1 (2.6%), 36 patients as type 2 (46.2%), 33 patients
      as type 3 (42.3%), and 7 patients as type 4 (9%). Preoperatively, there were no
      clinical differences depending on Roussouly's type of back. Pelvic incidence (P <
      0.001), sacral slope (P < 0.001), lumbar lordosis (P < 0.001), and spinosacral
      angle (P < 0.001) were different between the Roussouly's types of back.
      Postoperative clinical outcome improved (P < 0.001) but did not vary according to
      the Roussouly types except for leg pain VAS (P = 0.03). Post hoc tests did not
      reveal difference between the Roussouly's types and leg pain VAS. Postoperative
      radiographic outcomes did not change excepted for the lumbar lordosis (P <
      0.001), thoracic kyphosis (P = 0.007), and spinosacral angle (P = 0.02). The
      Roussouly type had no effect on the postoperative course of radiographic
      parameters. CONCLUSION: Equivalent clinical and radiographic outcomes have been
      highlighted independently of the increasing of the sacral slope for patients with
      one-level lumbar TDR. LEVEL OF EVIDENCE: 3.

PMID- 29461342
TI  - Leveraging Google Trends, Twitter, and Wikipedia to Investigate the Impact of a
      Celebrity's Death From Rheumatoid Arthritis.
AB  - BACKGROUND: Technological advancements, such as patient-centered smartphone
      applications, have enabled to support self-management of the disease. Further,
      the accessibility to health information through the Internet has grown
      tremendously. This article aimed to investigate how big data can be useful to
      assess the impact of a celebrity's rheumatic disease on the public opinion.
      METHODS: Variable tools and statistical/computational approaches have been used,
      including massive data mining of Google Trends, Wikipedia, Twitter, and big data
      analytics. These tools were mined using an in-house script, which facilitated the
      process of data collection, parsing, handling, processing, and normalization.
      RESULTS: From Google Trends, the temporal correlation between "Anna Marchesini"
      and rheumatoid arthritis (RA) queries resulted 0.66 before Anna Marchesini's
      death and 0.90 after Anna Marchesini's death. The geospatial correlation between
      "Anna Marchesini" and RA queries resulted 0.45 before Anna Marchesini's death and
      0.52 after Anna Marchesini's death. From Wikitrends, after Anna Marchesini's
      death, the number of accesses to Wikipedia page for RA has increased 5770%. From
      Twitter, 1979 tweets have been retrieved. Numbers of likes, retweets, and
      hashtags have increased throughout time. CONCLUSIONS: Novel data streams and big
      data analytics are effective to assess the impact of a disease in a famous person
      on the laypeople.

PMID- 29461343
TI  - Wong-Type Dermatomyositis Complicated by Interstitial Lung Disease.

PMID- 29461344
TI  - Confirmation of the Influence of Descending Aorta on Osteophyte Formation in
      Dish.

PMID- 29461345
TI  - Coexisting Systemic Sclerosis-Polymyositis and Sarcoidosis: Case Report and
      Review of the Literature.

PMID- 29461346
TI  - Medical Cannabis for the Treatment of Fibromyalgia.
AB  - BACKGROUND: Fibromyalgia is a chronic pain syndrome, characterized by chronic
      musculoskeletal pain, fatigue, and mood disturbances. There are nearly no data on
      the effect of medical cannabis (MC) treatment on patients with fibromyalgia.
      METHODS: Data were obtained from the registries of 2 hospitals in Israel (Laniado
      Hospital and Nazareth Hospital) on patients with a diagnosis of fibromyalgia who
      were treated with MC. After obtaining patient consent, demographic, clinical, and
      laboratory parameters were documented. All the patients also completed the
      Revised Fibromyalgia Impact Questionnaire regarding the period before and after
      MC treatment. RESULTS: Thirty patients were identified, and 26 patients were
      included in the study. There were 19 female patients (73%), and the mean age of
      the study group was 37.8 +/- 7.6 years. The mean dosage of MC was 26 +/- 8.3 g
      per month, and the mean duration of MC use was 10.4 +/- 11.3 months. After
      commencing MC treatment, all the patients reported a significant improvement in
      every parameter on the questionnaire, and 13 patients (50%) stopped taking any
      other medications for fibromyalgia. Eight patients (30%) experienced very mild
      adverse effects. CONCLUSIONS: Medical cannabis treatment had a significant
      favorable effect on patients with fibromyalgia, with few adverse effects.

PMID- 29461347
TI  - Debunking the "Myths" of Magnet(r).
AB  - Rebecca Graystone, the Magnet Program Director, dispels some myths about the
      Magnet Recognition Program(r). Ms Graystone encourages leaders interested in
      Magnet or those already designated to feel free to access resources including
      those of the Magnet Program Office.

PMID- 29461348
TI  - Electronic Staff Unit Meetings: A New Model.
AB  - This article discusses how a group of directors and nursing staff in a rural
      hospital created an innovative unit meeting model using electronic technology to
      communicate with staff in a more meaningful manner and still comply with
      regulatory requirements and 2-way information needs.

PMID- 29461349
TI  - Return on Investment for the Baccalaureate-Prepared RN in Ambulatory Care.
AB  - Evidence supports the return on investment for an RN in ambulatory care.
      Utilizing RNs to their fullest potential in ambulatory practices is essential to
      effectively manage population health. Bon Secours Health System launched a new
      role, patient navigator RNs, to ensure seamless transitions of complex patients
      across care settings, resulting in better patient outcomes and a financial
      return.

PMID- 29461350
TI  - Leading Change: A Case Study of the First Independent Critical-Access Hospital to
      Achieve Magnet(r) Designation.
AB  - OBJECTIVE: The aim of this study was to understand how nurses in a 25-bed
      critical-access hospital (CAH) led change to become the 1st to achieve Magnet(r).
      BACKGROUND: Approximately 21% of the US population lives in rural areas served by
      CAHs. Rural nurse executives are particularly challenged with limited resources.
      METHODS: Staff nurses, nurse managers, interprofessional care providers, the
      chief nursing officer, and board of directors (n = 27) were interviewed.
      Observations of hospital units and administrative meetings were done, and
      hospital reports were analyzed. RESULTS: Nine themes emerged to support a
      conceptual model of leading change. The CAH spent 3 years of its 6-year journey
      establishing organizational readiness. Nurses overcame complex challenges by
      balancing operational support and fostering relationships. The Magnet journey led
      to significantly improved nurse and patient outcomes. A new organizational
      culture centered on shared governance, evidence-based practice, and higher
      education emerged. CONCLUSIONS: The journey to Magnet leads to improved nurse,
      patient, and organization outcomes.

PMID- 29461351
TI  - An Innovative Partnership to Improve Student Health: Response to a Community
      Health Needs Assessment.
AB  - This community nursing partnership for student health is a well-recognized
      innovation, regionally and statewide. The initiative exemplifies 1 department of
      nursing's commitment to community involvement that originated from the forward
      thinking of nurse leaders. The journey to engaging intraprofessional partners and
      firmly establishing the partnership within the community is described.

PMID- 29461352
TI  - Implementation and Evaluation of Shared Medical Appointments in Veterans With
      Diabetes: A Quality Improvement Study.
AB  - OBJECTIVE: The aim of this study is to implement and evaluate shared medical
      appointments (SMA) in veterans with diabetes. BACKGROUND: Health systems are
      challenged to meet the complex care needs of veterans with diabetes. Use of SMA
      has resulted in significant improvements in A1c, blood pressure, and self
      management skills in this population. METHODS: Shared medical appointments were
      implemented in a Veterans Administration Health System. A1c, blood pressure,
      total cholesterol, high-density lipoprotein, low-density lipoprotein,
      triglycerides, weight, and height were collected at baseline, 3 months, and 6
      months; hospitalization anytime; and veteran satisfaction at baseline and 6
      months. RESULTS: From October 15, 2015, to March 15, 2016, 30 male veterans with
      diabetes participated in monthly SMA. Outcome measures except for high-density
      lipoprotein improved significantly (P < .02) from baseline to 6 months. No
      veterans were hospitalized. Veteran satisfaction increased significantly (P <
      .001). CONCLUSION: Shared medical appointment can be a highly effective
      intervention for veterans with diabetes. Nursing leaders need to be at the
      forefront of implementing SMA for populations with chronic conditions.

PMID- 29461353
TI  - Realigning Shared Governance With Magnet(r) and the Organization's Operating
      System to Achieve Clinical Excellence.
AB  - In 2012, an academic medical center successfully overhauled a 15-year-old shared
      governance to align 6 house-wide and 30 unit-based councils with the new Magnet
      Recognition Program(r) and the organization's operating system, using the
      processes of LEAN methodology. The redesign improved cross-council communication
      structures, facilitated effective shared decision-making processes, increased
      staff engagement, and improved clinical outcomes. The innovative structural and
      process elements of the new model are replicable in other health institutions.

PMID- 29461354
TI  - A Nursing Leadership Immersion Program: Succession Planning Using Social Capital.
AB  - This article describes the inception and evolution of a 3-month immersion
      experience between hospital and nurse leaders where sociological principles were
      applied to support nurse leader succession. Unique to this program, the bedside
      nurse joins the nursing executive team full time to participate in all
      organizational leadership activities as part of the experience.

PMID- 29461355
TI  - Health, Well-being, and Health Care Access in Rural Communities: Comparing Latino
      and Non-Latino White Low-income Families.
AB  - This study explores how low-income rural Latino children and their mothers differ
      from their non-Latino white counterparts in terms of health, well-being, and
      health care access. A subsample of non-Latino white (n = 201) and Latino (n =
      157) children and their mothers was drawn from the Rural Families Speak about
      Health Project, a multistate, cross-sectional data set developed through mixed
      purposive sampling methods. Findings suggest that Latino children's families were
      disadvantaged in terms of child health and access to health care, whereas non
      Latino white children's families were disadvantaged in terms of child behavior
      problems and maternal health and depression.

PMID- 29461356
TI  - There and Back Again: How the Repeal of ACA Can Impact Community Health Centers
      and the Populations They Serve.
AB  - We examined the impact of Medicaid expansion on rates of the remaining uninsured
      at the federally qualified health center level by race/ethnicity, limited English
      proficiency, and poverty status of their patients. Results indicated a systematic
      disadvantage in nonexpansion states for federally qualified health centers with
      high concentrations of these populations and an advantage in expansion states for
      federally qualified health centers with fewer limited English proficiency
      patients. Our findings highlight the importance of maintaining the Affordable
      Care Act in reducing disparities in coverage and the importance of federal
      funding to continue services for the remaining uninsured and vulnerable
      populations in both expansion and nonexpansion states.

PMID- 29461357
TI  - The Effects of a Health Promotion Program on Rural, West Virginia Adults.
AB  - This health promotion project is a 12-week program for adults in a rural West
      Virginia community with a body mass index (BMI) of 25 or greater. The goals of
      this project were to facilitate learning through modules focusing on activity and
      nutrition, increase knowledge of healthy activity and nutrition, and improve
      weight and BMI. Each 12-week session provided evidenced-based information
      regarding obesity, physical activity, and nutrition. Participants completed pre-
      and postprogram and 1-month follow-up survey/questionnaire. Results were compared
      for changes in activity, nutrition, and BMI. The program resulted in positive
      changes: increase in activity and nutritional consumption and a decrease in BMI.

PMID- 29461358
TI  - Obstetric Access and the Community Health Imperative for Rural Women.
AB  - This study examined whether the closure of several inpatient obstetric units in
      rural New Hampshire affected birth outcomes. It is a secondary analysis of birth
      certificate data from 2005 through 2012 and includes 5881 births. There were no
      changes in perinatal outcomes. When examining outcomes based on distance
      travelled to place of birth, controlling for closures, women who traveled greater
      than 30 miles had fewer prenatal visits and lower birth weight and gestational
      age infants. Community services that provide prenatal care and/or home visiting
      are even more important when obstetric units are not available in the community.

PMID- 29461359
TI  - The Relationship Between Expressed Emotion and the Probability of Suicide Among
      Turkish Psychiatric Outpatients: A Descriptive Cross-sectional Survey.
AB  - The purpose of this study is to examine expressed emotion and the relationship
      between expressed emotion and suicide probability in psychiatric outpatients (N =
      350). Patients who did not receive support from anyone scored higher on the Level
      of Expressed Emotion (LEE) Scale than those who were supported by family,
      friends, or their physician provider. Scores by patients, who selected their
      spouse as a key person, scored higher on the LEE than those who chose one of
      their children. Spouses on the LEE were often depicted as being more intrusive,
      reactive, and intolerant when compared with their children. The probability of
      suicide increased as the LEE scores on expressed emotion increased.

PMID- 29461360
TI  - Parenting Stress in Fathers of Children With Type 1 Diabetes.
AB  - The purpose of the present study was to evaluate generic and pediatric parenting
      stress in an international sample of fathers of children with type 1 diabetes.
      Two-hundred forty-nine fathers of children ages 2 to 10 years with type 1
      diabetes completed the Parenting Stress Index, Pediatric Inventory for Parents,
      Dads' Active Disease Support Scale (DADS), Self-Care Inventory, and a
      demographic/disease-related questionnaire online. More frequency of pediatric
      parenting stress was associated with greater general parenting stress (r = -0.25,
      P < .001), DADS Involvement (r = 0.18, P < .01). The present findings suggest
      that paternal involvement in management of the child's T1 can have meaningful
      implications for disease management outcomes.

PMID- 29461362
TI  - Journal Article Reviews: Erratum.

PMID- 29461361
TI  - Health and Health Care From the Perspective of Intimate Partner Violence Adult
      Female Victims in Shelters: Impact of IPV, Unmet Needs, Barriers, Experiences,
      and Preferences.
AB  - Intimate partner violence (IPV) predicts poor health for victims and their
      children, but little is known about the perspective of victims. This study
      reports the perspectives of adult female IPV victims about the impact of IPV on
      their health and barriers of health care access for themselves and their
      children. The majority rated their health as good to excellent (69%). However,
      83.5% indicated that IPV negatively affected their health; 53.5% had unmet health
      care needs. Mental health care was the most common unmet need for women;
      children's unmet needs were immunizations and preventive care. Transportation
      difficulties posed the biggest barrier to health care access.

PMID- 29461363
TI  - Hemodynamic Assessment with SPY-Indocyanine Green Angiography in Expansion
      Period: A Study for Expansion Capsule Pressure Optimization.
AB  - Tissue expansion-related severe complication exists, and the poor blood supply is
      one of the causes. After decades of negative correlation between capsule pressure
      and blood flow was verified, the widely recognized expansion capsule pressure is
      still absent. A prospective randomized controlled trial was performed to explore
      the optimal expanding capsule pressure. Thirty subjects were randomly divided
      into 5 groups, received a weekly expanding on 60-, 70-, 80-, 90-, and 100-mm Hg
      capsule pressure, respectively. All patients achieved 8-week follow-up;
      hemodynamic assessment by SPY-indocyanine green (ICG) angiography was taken every
      2 weeks. Standardized indexes from SPY-ICG angiography were used to assess the
      blood supply, in which the ratio of ingress rate and the ingress rate of normal
      skin (IR/NIR) reflects the arterial perfusion level, and the ratio of Engress
      Rate and IR (ER/IR) indicates the venous reflux level. The expansion-related
      adverse events during the trial were recorded. The IR/NIR and the ER/IR are both
      obviously negatively correlated to the capsule pressure of tissue expander (P <=
      0.05, the ER/IR's correlation coefficient = -0.453; the IR/NIR's correlation
      coefficient = -0.482). The post-expansion IR/NIR increased significantly after 8
      weeks of expansion (P <= 0.05) in 90-mm Hg group. And the post-expansion ER/IR
      was significantly elevated (P <= 0.05) in 80 and 90-mmHg groups. There were 2
      expansion-related complications reported in 100-mm Hg group, whereas no
      complication occurred in 4 other lower groups. SPY-ICG angiography is an
      objective measurement for tissue expansion hemodynamic monitoring. The expanding
      capsule pressure of 80 to 90 mm Hg is a reasonable upper limit.

PMID- 29461364
TI  - The Effect of Unfocused Extracorporeal Shock Wave Therapy on Bone Defect Healing
      in Diabetics.
AB  - AIM: The purpose of this study was to evaluate the effect of the unfocused
      extracorporeal shock wave therapy (ESWT) on healing of mandible ramus defects in
      diabetic rats. MATERIAL AND METHOD: Forty male Wistar albino rats were used in
      the experiment. All animals were randomly divided into 2 main groups, nondiabetic
      and diabetic. Critical-sized defects were created on ramus in all rats. ESWT was
      performed to half of rats in each group at 3 sessions after surgery. Animals were
      euthanized at either fourth or eighth week. Stereological and radiologic
      examination was performed. Data were statistically analyzed by one-way variance
      analysis and Tukey post-hoc test. RESULTS: Hounsfield Unit values were higher in
      DE group than DE group in both 8-week and 4-week groups (P > 0.05). In both 4
      week and 8-week diabetic groups, higher value was observed when compared with
      nondiabetic groups (P > 0.05). According to stereological results, in 4-week
      groups, there was a higher new bone, connective tissue, and neovascularization
      volume in DE group than DE group and in DE group than DE group. These results are
      similar for the 8-week groups except NV volume. CONCLUSION: It was found that
      ESWT application has no positive effect on the healing of critical-sized bone
      defects in nondiabetics whereas promising effects in diabetics were observed.

PMID- 29461366
TI  - Long-Term Skeletal Changes After Maxillary Distraction Osteogenesis in Growing
      Children With Cleft Lip/Palate.
AB  - PURPOSE: To systematically evaluate the skeletal changes after maxillary
      distraction osteogenesis (DO) in growing patients with cleft lip with or without
      cleft palate (CL/P). MATERIALS AND METHODS: Electronic databases, gray
      literature, and reference list searches were conducted. Articles reporting
      prospective and retrospective studies that included patients <16 years old (N >=
      6) who had received DO surgery for correction of a midfacial hypoplasia due to
      CL/P, and the period of follow-up persisted >1 year were reviewed. The original
      articles were evaluated by 2 investigators to ensure that they met the selection
      criteria. A methodologic quality assessment tool was used to evaluate the quality
      of selected studies. Twenty-six studies met the initial search criteria, and 9
      articles included 101 growing patients with maxillary hypoplasia due to CL/P who
      received DO surgery were finally selected and analyzed. RESULTS: The results
      showed that long term after maxillary advancement with DO, the horizontal relapse
      in A-point was <15% in 3 studies, 20% to 25% in 1 study, 30% to 35% in 3 studies,
      and >40% in 1 study. Totally, the range of horizontal relapse in A-point was
      11.9% to 45.9%. Similarly, the relapse in SNA angle was <30% in 1 study, 30% to
      40% in 3 studies, and >40% in 2 studies. Totally, the range of relapse in SNA was
      25.7% to 77%. Two studies showed that the vertical relapse in A-point were 137%
      and 208%, and in the PNS point were 65% and 62.7%. CONCLUSION: Although findings
      demonstrated that DO is an effective treatment method for severe maxillary
      hypoplasia in growing patients with CL/P, there is a relatively high amount of
      skeletal relapse both in horizontal and vertical dimension. Thus, the first
      proposed alternative for CL/P patients would be to select the correct primary
      procedure to decrease damage and avoid unnecessary scars. Then appropriate
      preoperative and postoperative care is necessary to prevent postoperative
      relapse. In addition, overcorrection also may be a possible alternative for
      compensation of postoperative relapse.

PMID- 29461365
TI  - Alternatives to Autologous Bone Graft in Alveolar Cleft Reconstruction: The State
      of Alveolar Tissue Engineering.
AB  - Alveolar cleft reconstruction has historically relied on autologous iliac crest
      bone grafting (ICBG), but donor site morbidity, pain, and prolonged
      hospitalization have prompted the search for bone graft substitutes. The authors
      evaluated bone graft substitutes with the highest levels of evidence, and
      highlight the products that show promise in alveolar cleft repair and in
      maxillary augmentation. This comprehensive review guides the craniofacial surgeon
      toward safe and informed utilization of biomaterials in the alveolar cleft.A
      literature search was performed to identify in vitro human studies that fulfilled
      the following criteria: Level I or Level II of evidence, >=30 subjects, and a
      direct comparison between a autologous bone graft and a bone graft substitute. A
      second literature search was performed that captured all studies, regardless of
      level of evidence, which evaluated bone graft substitutes for alveolar cleft
      repair or alveolar augmentation for dental implants. Adverse events for each of
      these products were tabulated as well.Sixteen studies featuring 6 bone graft
      substitutes: hydroxyapatite, demineralized bone matrix (DBM), beta-tricalcium
      phosphate (TCP), calcium phosphate, recombinant human bone morphogenic protein-2
      (rhBMP-2), and rhBMP7 fit the inclusion criteria for the first search. Through
      our second search, the authors found that DBM, TCP, rhBMP-2, and rhBMP7 have been
      studied most extensively in the alveolar cleft literature, though frequently in
      studies using less rigorous methodology (Level III evidence or below). rhBMP-2
      was the best studied and showed comparable efficacy to ICBG in terms of volume of
      bone regeneration, bone density, and capacity to accommodate tooth eruption
      within the graft site. Pricing for products ranged from $290 to $3110 per 5
      mL.The balance between innovation and safety is a complex process requiring
      constant vigilance and evaluation. Here, the authors profile several bone graft
      substitutes that demonstrate the most promise in alveolar cleft reconstruction.

PMID- 29461367
TI  - The Natural History of Cranial Morphology in Sagittal Craniosynostosis.
AB  - BACKGROUND: Children with craniosynostosis have abnormal head shapes. Parents
      frequently ask whether the abnormal head shape will get worse with time. However,
      there is no information in the literature to indicate whether the deformity gets
      worse. OBJECTIVE: To assess the progression of cranial morphology in children
      with unoperated craniosynostosis. METHODS: A retrospective review of all children
      with unoperated sagittal craniosynostosis who were referred to the Craniofacial
      Clinic at the Hospital for Sick Children (SickKids) was conducted. Serial 3D
      photographs of patients with sagittal craniosynostosis who have not undergone
      surgical correction were included in the study. There were 14 cases included,
      with 9 males and 5 females. Ages at time of scans ranged from 3 months to 5 years
      of age (mean = 28.3 months, SD = 28.2 months). Nine patients had the first scan
      at age of <12 months. Multiple scans for each patient were sized for volume over
      time and compared with a normative skull database. RESULTS: The results of
      measuring skull volume changes over time revealed no significant difference from
      infants without craniosynostosis. Furthermore, there cranial index was stable
      over time in patients with craniosynostosis. CONCLUSION: The severity of
      craniosynostosis does not worsen or improve with time. Parents having difficulty
      in deciding to proceed with surgical correction of craniosynostosis can be
      reassured that the skull deformity will remain stable with the growth of their
      child if they decide not to proceed with surgical correction.

PMID- 29461368
TI  - Safety Outcomes in Endoscopic Versus Open Repair of Metopic Craniosynostosis.
AB  - BACKGROUND: Premature fusion of the metopic suture leads to a range of clinical
      presentations, with more severe patients presenting characteristically with
      trigonocephaly. Endoscopic-assisted correction of craniosynostosis is emerging as
      an alternative to the gold-standard open cranial vault remodeling. While there
      are several documented benefits of endoscopic correction, the management of
      craniosynostosis varies widely in the literature with little consensus as to the
      preferred timing and surgical technique for repair. The purpose of this study was
      to investigate the safety outcomes of endoscopic versus open surgery at our
      institution. METHODS: This retrospective cohort study included all patients
      diagnosed with metopic craniosynostosis who underwent open or closed surgical
      management and received at least 6 months of follow-up. Data extraction was
      performed via chart review and included demographic information and safety
      outcome variables. RESULTS: During the study period, 17 patients who met our
      inclusion criteria were treated by the multidisciplinary craniofacial team at our
      institution. Eight patients underwent endoscopic surgery and 9 underwent open
      surgery. The mean age at surgery was significantly higher in the open surgery
      group than the endoscopic surgery group (13.7 months versus 2.3 months,
      respectively). Estimated blood loss, percent estimated blood volume lost,
      transfusion volume, procedure length, hospital length of stay, and intensive care
      unit (ICU) length of stay were all significantly higher in the open surgery group
      compared with the endoscopic group. CONCLUSIONS: In our patient population,
      endoscopic surgery for metopic craniosynostosis had an improved safety profile
      versus open surgery based on reduced procedure length, estimated blood loss,
      volume of blood transfusion, and length of stay in the ICU and hospital.

PMID- 29461369
TI  - Reevaluation of Mandibular Morphometry According to Age, Gender, and Side.
AB  - AIM: This study aims to reevaluation the linear and angular measurements of
      mandibles with multidetector computed tomography (MDCT) that is a new method and
      used frequently in recent years. MATERIALS AND METHODS: The archived MDCT images
      of 100 adult patients (age range, 15-74 years) without mandibular operation and
      trauma history were evaluated retrospectively. Mandibular ramus heights, maximal
      mandibular length, mandibular symphysis height, mandibular angles, and mandibular
      foramen distance measurements were performed on MDCT images. All measurement
      parameters were analyzed by gender, age groups, and sides. RESULTS: Mandibular
      linear length measurements were higher in males than in females (P < 0.05). Only
      mandibular symphysis height was statistically significantly different in age
      groups (P < 0.05). The Angle 1 (gonial angle) was found to be significantly
      higher in females (P < 0.05). The Angle 3 (right condyle-gnathion-left condyle
      angle) was observed to be significantly higher in the 60+ age group (P < 0.05).
      The 3 of the mandibular foramen measurements (distance from the front edge,
      distance to gonion, and height of lingula) were found to be higher in males than
      in females (P < 0.05). There were no significant differences according to age
      groups in these measurements. The lengths of the mandibular canals were higher in
      males (44.72 mm) than in females (41.68 mm). There was no statistically
      significant difference was found between gender, age groups, and sides of
      mandibular canal length. CONCLUSION: The MDCT was found to be a reliable method
      for the detection of mandibular morphometry when compared with the results of
      other radiographic images studies.

PMID- 29461370
TI  - Nasal Cavity Actinomycosis Mimicking Rhinolith.
AB  - Actinomycosis is a subacute-to-chronic bacterial infection caused by filamentous,
      gram-positive, non-acid-fast, anaerobic-to-microaerophilic bacteria. It is
      characterized by continuous spread, suppurative and granulomatous inflammation,
      and formation of multiple abscesses and sinus tracts that may discharge sulfur
      granules. Although the most common clinical forms of actinomycosis are
      cervicofacial, involvement of the nose and paranasal sinuses are extremely rare.
      Furthermore, nasal cavity actinomycosis mimicking rhinolith has not been reported
      in the literature previously. This article reports a patient of nasal cavity
      actinomycosis causing symptoms similar to those of a rhinolith, which was
      successfully treated by surgical debridement and antibiotic therapy.

PMID- 29461371
TI  - Facial Artery as a Recipient Vessel for Extensive Scalp Reconstruction With Free
      Omental Flap Without Vein Graft.
AB  - Most patients with reconstruction for extensive scalp defects require the use of
      a free flap. The suitability of the recipient vessel has a major impact on the
      surgery and postoperative outcome. Flaps that can be used to reconstruct the
      total scalp with a single flap include the latissimus dorsi (LD) and omental
      flaps; the LD flap is generally preferred since the omental flap results in
      relatively larger donor site morbidity. The recipient vessel most commonly used
      for scalp defect reconstruction is the superficial temporal vessel. The authors
      report a patient with successful total scalp reconstruction using a free omental
      flap on a patient whose bilateral superficial temporal arteries could not be used
      and who did not have available LD on both sides due to previous LD free flap
      surgeries for recurrent scalp angiosarcoma. In this patient, direct anastomosis
      of the flap to the right facial artery was performed without pedicle lengthening,
      such as vein graft or arteriovenous loops, and favorable outcome was achieved in
      terms of facial contour after recovery. The free omental flap is useful for
      reconstruction of extensive scalp defects without additional complex surgical
      procedures when other flaps are not viable or when the recipient vessel is
      located at a far distance.

PMID- 29461372
TI  - A Standard Operating Procedure of Clean and Fast Craniotomy Without Application
      of Raney Clips.
AB  - Clean and fast craniotomy and closure (CAC) is a fundamental part of modern
      microneurosurgery, and is an essential technique that young neurosurgeons shall
      master. The hemostatic instruments of CAC have evolved from forceps to raney
      clips. Thanks to the wide application of bipolar coagulation, local infiltration
      anesthesia combined with cauterization is become an effective method of
      hemostasis. The authors worked out a standard operating procedure (SOP) of CAC
      assisted by fishhooks without the application of raney clips. According to the
      authors' experience, the average time spent on CAC decreased from more than 1
      hour to <40 minutes. Owning to little bleeding, the operative field is clean
      throughout the procedure. Patients also experience less pain and enjoy an earlier
      discharge. With few complications, the authors believe that this cost-effective
      SOP may become a cornerstone of early recovery after surgery.

PMID- 29461373
TI  - Single Session Facial Lipostructure by Using Autologous Fat Mixed With Platelet
      Rich Fibrin Injected by Using Facial Autologous Muscular Injection Technique.
AB  - AIM: This study was designed to evaluate the role of single session autologous
      facial fat grafting in correcting facial asymmetries after mixing it with
      platelet-rich fibrin (PRF) and injecting them into rich vascular facial muscular
      plane. MATERIALS AND METHODS: Fifteen patients (12 females and 3 males) with age
      ranging from 18 years to 40 years were included in this study and followed up
      during 6 months, all the patients were treated in the Al-Shaheed Ghazi Al-Hariri
      for specialized surgeries hospital (Medical City, Baghdad, Iraq).Autologous fat
      with PRF injected in facial muscular plane was the standardized method in the
      treatment of acquired and congenital facial defects.Results were evaluated by 2
      plastic surgeons using visual analogue scale.Interexaminer and intraexaminer
      calibration of the visual analogue scale were carried out by using paired t test.
      RESULTS: This prospective study showed that the majority of patients (73.3%)
      needed only a single session for creating a noticeable improvement in facial
      volumes and contours. CONCLUSIONS: Mixing fat with PRF and injecting them by
      using facial autologous muscular injection technique offers better graft survival
      by utilizing the growth factors and cytokines in PRF clot together with rich
      vascular plexus in the muscular layer consequently.

PMID- 29461374
TI  - Crushed Cartilage: A Rescue Procedure in Rhinoplasty.
AB  - While the use of crushed cartilage is now universally recognized as a valid
      procedure in rhinoplasty to mask irregularities and eliminate slight deficits,
      there is still no consensus as to the optimal degree of crushing and the rate of
      graft resorption over time. With a view to casting light on these 2 important
      aspects and providing some guidelines, the authors present a study of 123
      patients subjected to grafts of cartilage with different degrees of crushing in
      the different areas of the nasal pyramid: upper third (45 patients), middle third
      (40), and lower third (38). The degree of crushing was medium for 95 patients and
      high for 28 who presented thinner and less elastic skin. Comparison of the
      performance over time of the cartilage grafts inserted in the same areas but with
      different degrees of crushing provides important indications as regard the best
      way of preparing the material. The results proved satisfactory with improvements
      for all of the 95 patients subjected to grafts of moderately crushed cartilage.
      The initial defect was instead still present, albeit with some partial
      improvement, at a distance of 12 months in 17 of the 28 patients where highly
      crushed cartilage was used. The study suggests that a moderate degree of crushing
      offers better results as regard flexibility and stability over time.

PMID- 29461375
TI  - Parotid Mucoepidermoid Carcinoma Mimicking a Large Mucocele.
AB  - Mucoepidermoid carcinoma is a malign tumor involving the parotid gland and minor
      salivary glands. Parotid pure cystic mucoepidermoid carcinoma can also masquerade
      mucocele, and hence, histopathological examination is crucial to distinguish the
      2. Herein, the authors report a patient of mucoepidermoid carcinoma presenting as
      an asymptomatic mucocele-like cystic parotid mass. A 69-year-old female presented
      with cystic parotid mass; her examination findings and diagnostic imaging were
      consistent with that of mucocele. Histological examination revealed
      mucoepidermoid carcinoma. This case indicates that parotid mucocele-like cysts
      should be included in the differential diagnosis of malign salivary gland tumors.

PMID- 29461376
TI  - Modified Unilateral Pedicled V-Y Advancement Flap for Scalp Defect Repair.
AB  - Reconstruction of scalp defects caused by tumor resection or trauma is very
      challenging. A majority of the surgeons prefer to use local flap rather than skin
      graft or free flap for scalp defects repair. The aim of this study is to
      investigate the technique of modified unilateral pedicled V-Y advancement flap
      for the reconstruction of scalp defect.A retrospective review was performed in a
      series of 18 patients who had a modified unilateral pedicled V-Y advancement flap
      to restore scalp defect from May 2013 to January 2017. Their mean age is 58 (24
      78) years. These patients suffered from basal cell carcinoma, seborrhoeic
      keratosis, squamous cell carcinoma, or trauma on the scalp. All of them underwent
      preoperative Doppler scanning to identify the scalp arteries and then
      individually designed. The flap size ranged from 33 * 50 mm to 68 * 105 mm.
      Patients were followed for an average of 12 months postoperatively (ranged from 6
      to 37 months). No major complications occurred, only 2 cases had a minor distal
      epidermal necrosis or obstruction of venous backflow observed for the first 3
      days of the surgery, and they both healed well. Modified unilateral pedicled V-Y
      flap technique with fairly rapid recovery and acceptable reorientation of hair
      follicles leads to esthetical outcome and patient satisfaction. Most importantly,
      no tumor recurrence at the original site during the follow-up period was seen.The
      modified unilateral pedicled V-Y advancement flap is a simple but efficient
      technique, particularly suitable for the repair of small and medium size scalp
      defects with advantages including the safety of the procedure and overall
      esthetic results like hairline preservation and less scarring when compared to
      other local flap techniques.

PMID- 29461377
TI  - Total Lower Lip Reconstruction With Functional Gracilis Free Muscle Flap.
AB  - Free flaps based on static slings principles cannot provide esthetic and
      functional outcomes at a desired level in total or close to total lip loss.
      Therefore, dynamic methods have become a current issue in recent years and
      especially the idea of functional gracilis free muscle flap has been suggested.
      In this study, we present a case of a successful total lower lip repair with this
      flap.In a 78-year-old female patient who was diagnosed with squamous cell
      carcinoma involving the entire lower lip, bilateral modified radical neck
      dissection and full-thickness total resection with 1 cm surgical margin so as to
      include both commissures of the tumor were performed and then a free gracilis
      muscle flap was transferred from the same side. After microvascular anastomoses,
      the motor nerve of the flap was coapted to the marginal mandibular branch of the
      fascial nerve. The entire intra- and extraoral surfaces of the flap were covered
      with a partial-thickness skin graft which was taken from the right thigh. There
      was no any intra- or early postoperative complication. The skin graft and flap
      survived without any problem.In the controls of the patient who was followed-up
      for 8 postoperative months, it was observed that the gracilis muscle flap was
      well-adapted to its place, gained a very good tonus, its volume reduced over time
      and reached to ideal dimensions, and the overlying skin graft provided a good
      color and texture match with the surrounding tissues. The motor activity of the
      muscle was monitored with the Tinel's test. The speech and facial expressions of
      the patient were very clear. Despite the patient has an edentulous mandible and
      was not using prosthesis, her feeding with fluid and solid foods was free of
      problems, oral competence was highly sufficient, and there was no any drooling.
      Esthetic appearance was very good and intraoral vestibular depth was sufficient.
      The mouth opening was 3 cm. When comparing with upper orbicularis oculi muscle on
      the electroneuromyography (ENMG) ordered at the 8th month, a similar nerve
      conduction time (3.3 versus 3.8 ms) and contraction amplitude (0.5 versus 0.4 mV)
      values were obtained from the gracilis muscle. Follow-up of the patient is still
      continued with no tumor recurrence observed during this period.Being the real
      dynamic flap and its tonus of the functional gracillis free muscle flap in
      opposite to the static methods provides a significant superiority over the other
      options in terms of oral functions; moreover, the overlying skin graft presents a
      very good color and texture harmony aesthetically. This method is a candidate to
      be an exclusive surgical technique in the repair of total or close to total lip
      losses in the future.

PMID- 29461378
TI  - Do You Have a Writing Mentor?

PMID- 29461379
TI  - Understanding Poverty: Teaching Social Justice in Undergraduate Nursing
      Education.
AB  - AIM: This article presents results of an exploratory qualitative study examining
      gains in empathy and social justice beliefs among undergraduate nursing students.
      BACKGROUND: As undergraduate nursing education provides the foundation for future
      forensic nurses, developing successful methods to increase beliefs and behaviors
      of social empathy and social justice among nursing students will have a
      beneficial effect on the specialty of forensic nursing. As such, a team of
      nursing researchers explored the effects of a poverty simulation on the social
      empathy and social justice beliefs held by undergraduate students. METHOD: The
      research team conducted an exploratory qualitative study of student reflective
      journals. Using an inductive interpretive process, the researchers performed a
      content analysis of student responses. RESULTS: The researchers identified three
      constitutive patterns and eight supporting themes as reflected in the students'
      reflective journals after participation in poverty simulation sessions.
      CONCLUSION: This research study found that, when nursing students participate in
      poverty simulation experiences, they gain an increased understanding of the
      vulnerability and complexities of living in poverty and are motivated to both
      advocate for patients and become change agents. APPLICATION: Such increases in
      social empathy and promotion of social justice will inevitably positively affect
      their future practice and inform their development as forensic nurses.

PMID- 29461380
TI  - What Does the Implementation of Peer Care Training in a U.K. Prison Reveal About
      Prisoner Engagement in Peer Caregiving?
AB  - The number of aging and chronically ill prisoners continues to rise within the
      United Kingdom prison demography; consequentially, many institutions face health
      and social care crises of immense proportions. The needs of this group are both
      complex and costly, and in the United Kingdom, this is set to a backdrop of
      overcrowding, increasing violence, and public spending cuts in line with
      government austerity targets. In this context, the development of prisoner peer
      caregiving is proposed as an approach to mitigating the effects of aging,
      disability, and illness. A qualitative study was implemented to design, deliver,
      and evaluate a peer care training intervention within a U.K. prison. The
      perceptions of six prisoner peer caregivers are represented in this article.
      Thematic analysis of interview transcripts identified challenges experienced by
      peer caregivers in practice as well as recommended practical solutions. The
      social processes underpinning prisoner peer caregiving are discussed, including
      individual and organizational impediments to the fulfillment of their role.
      Practice theory, social learning theory, and criminological sensitivities were
      used as theoretical lenses to analyze the findings.

PMID- 29461381
TI  - Cultural Humility: An Active Concept to Drive Correctional Nursing Practice.
AB  - Correctional nursing practice is focused on a unique patient population: inmates
      who present with their own ethnicities and have an imposed culture from the
      prison structure. As such, culture must be considered to provide holistic care.
      Madeleine Leininger's Theory of Culture Care Diversity and Universality, which
      maintains that care is the essence of nursing (without inclusion of culture,
      there is no care), suggests three nursing actions: to maintain the patient's
      culture, make accommodations for it, and/or repattern cultural ways that may be
      unhealthful. Given that correctional nurses work within the context (and culture)
      of custody, Leininger's nursing actions may not always be feasible; however,
      showing an underlying attitude of cultural humility is. In this article, cultural
      humility, the basis of culturally competent care, is described in a manner that
      can drive nursing practice in corrections.

PMID- 29461382
TI  - Factors That Influence Mandatory Child Abuse Reporting Attitudes of Pediatric
      Nurses in Korea.
AB  - PURPOSE: This study aimed to identify knowledge of child abuse, awareness of
      child abuse reporting, factors that influence attitudes toward mandatory
      reporting, and professionalism among a sample of pediatric nurses in Korea.
      METHODS: One hundred sixteen pediatric nurses working at two university hospitals
      in Korea took part in the study and completed self-administered questionnaires.
      The data were analyzed using descriptive statistics, t tests, analysis of
      variance, Pearson correlation coefficients, and hierarchical regression analysis.
      RESULTS: Knowledge of child abuse, awareness of child abuse reporting, and
      attitudes toward mandatory reporting were low. Regarding nursing professionalism,
      social perceptions had the lowest mean score and nursing autonomy had the highest
      mean score. Attitudes toward mandatory reporting significantly correlated with
      professionalism. In the hierarchical regression model, the influences of nursing
      autonomy and intentions to report child abuse on attitudes toward mandatory
      reporting were statistically significant (F = 2.176, p = .013), explaining 32% of
      the variation in attitudes toward mandatory reporting. CONCLUSION: The results of
      this study could be used to improve systems and policies addressing child abuse
      and to further develop reporting procedures for identifying children at risk of
      abuse, to ensure their protection as a professional responsibility.

PMID- 29461384
TI  - Characteristics of Forensic Patients in California With Dementia/Alzheimers
      Disease: Erratum.

PMID- 29461383
TI  - Evaluating Nurse Practitioners Perceived Knowledge, Competence, and Comfort Level
      in Caring for the Sexually Abused Child.
AB  - OBJECTIVE: The purpose of this project was to evaluate nurse practitioners'
      (NPs') current approach and self-reported competence in the care of the sexually
      abused child in the primary care setting. METHODS: A 50-question survey was
      distributed to 5,734 NPs who were members of a state nursing organization and
      nursing alumni. Inclusion criteria included NPs caring for pediatric patients in
      a primary care setting in New York State. RESULTS: A total of N = 325 responses
      were obtained, and 110 participants met the inclusion criteria. Very few NPs felt
      competent to perform a medical forensic examination on a sexually abused child
      (25.5%), and even fewer felt competent to render a definitive opinion on sexual
      abuse (17.3%) or to testify in court (12.7%). Most NPs felt the need for more
      training on child sexual abuse (78.2%). Most would prefer to refer children who
      are suspected of sexual abuse to an expert (77.3%), but very few (19.1%) are
      being referred to a local resource, like a Child Advocacy Center when a parent
      calls the office with a concern. CONCLUSION: More research is needed to evaluate
      clinical practices regarding child sexual abuse. NPs see value in pursuing
      specialist referrals for child sexual abuse but do not have access to the
      appropriate resources or are unaware of the availability within their community.
      PRACTICE IMPLICATIONS: NPs should be aware of their own limitations and seek out
      education to improve their knowledge and skills. Forensic nurses are ideally
      situated to provide education on the available resources and the recommended
      clinical guidelines for referral.

PMID- 29461385
TI  - Understanding Poverty: Teaching Social Justice in Undergraduate Nursing
      Education.

PMID- 29461386
TI  - Cardiovascular Disease Risk Factors in Quebec Male Firefighters.
AB  - OBJECTIVE: We aimed to document the prevalence of cardiovascular disease (CVD)
      risk factors and symptoms in Quebec firefighters. METHODS: Seven hundred and
      seventy-nine (779) male firefighters (age: 41.6 +/- 10.4 years; body mass index
      [BMI]: 28.0 +/- 3.6 kg/m) answered an online questionnaire evaluating lifestyle
      and the presence of CVD risk factors and symptoms. RESULTS: The prevalence of
      obesity (BMI is more than or equal to 30 kg/m), diagnosed hypertension, diagnosed
      dyslipidemia, and diagnosed type 2 diabetes mellitus was respectively 23.6%,
      12.2%, 17.4%, and 1.7%. Among survey participants, 34.5% were categorized as
      moderate and 43.6% as high CVD risk, according to American College of Sports
      Medicine guidelines. CONCLUSIONS: A high proportion of Quebec firefighters are at
      moderate to high risk of CVD. These findings suggest that Quebec fire departments
      should help all firefighters to adopt and maintain a healthy lifestyle.

PMID- 29461387
TI  - Organizational Wellness Program Implementation and Evaluation: A Holistic
      Approach to Improve the Wellbeing of Middle Managers.
AB  - : Employee wellness programs can provide benefits to institutions as well as
      employees and their families. Despite the attempts of some organizations to
      implement programs that take a holistic approach to improve physical, mental, and
      social wellness, the most common programs are exclusively comprised of physical
      and nutritional components. In this study, we implemented a wellness program
      intervention, including training using a holistic approach to improve the
      wellbeing of middle managers in several multinational organizations. We included
      control and experimental groups to measure wellness and teamwork with two
      repeated measures. Our results indicated that employees receiving the
      intervention had improved measures of wellness and teamwork. A positive
      relationship was found between wellness and teamwork in the experimental group
      when compared with the control group. Taken together, the data suggest that
      implementation of these programs would provide valuable outcomes for both
      employees and organizations.

PMID- 29461388
TI  - Approaches to Patient Counseling Regarding Effectiveness of Oral Contraceptives.

PMID- 29461389
TI  - The Accuracy of Perioperative Noninvasive Blood Pressure Monitoring in Obese
      Patients.

PMID- 29461390
TI  - In Response.

PMID- 29461391
TI  - Bivalirudin for Pediatric Procedural Anticoagulation: A Narrative Review.
AB  - Bivalirudin (Angiomax; The Medicines Company, Parsippany, NJ), a direct thrombin
      inhibitor, has found increasing utilization as a heparin alternative in the
      pediatric population, most commonly for the treatment of thrombosis secondary to
      heparin-induced thrombocytopenia. Due to the relative rarity of heparin-induced
      thrombocytopenia as well as the lack of Food and Drug Administration-approved
      indications in this age group, much of what is known regarding the
      pharmacokinetics and pharmacodynamics of bivalirudin in this population has been
      extrapolated from adult data. This narrative review will present recommendations
      regarding the use of bivalirudin for procedural anticoagulation in the pediatric
      population based on the published literature.

PMID- 29461392
TI  - Combined Colloid Preload and Crystalloid Coload Versus Crystalloid Coload During
      Spinal Anesthesia for Cesarean Delivery: A Randomized Controlled Trial.
AB  - BACKGROUND: The optimal strategy of fluid administration during spinal anesthesia
      for cesarean delivery is still unclear. Ultrasonography of the inferior vena cava
      (IVC) has been recently used to assess the volume status and predict fluid
      responsiveness. In this double-blind, randomized controlled study, we compared
      maternal hemodynamics using a combination of 500-mL colloid preload and 500-mL
      crystalloid coload versus 1000-mL crystalloid coload. We assessed the IVC at
      baseline and at subsequent time points after spinal anesthesia. METHODS: Two
      hundred American Society of Anesthesiologists physical status II parturients with
      full-term singleton pregnancies scheduled for elective cesarean delivery under
      spinal anesthesia were randomly allocated to receive either 500-mL colloid
      preload followed by 500-mL crystalloid coload (combination group) or 1000-mL
      crystalloid coload (crystalloid coload group) administered using a pressurizer.
      Ephedrine 3, 5, and 10 mg boluses were administered when the systolic blood
      pressure decreased below 90%, 80% (hypotension), and 70% (severe hypotension) of
      the baseline value, respectively. The IVC was assessed using the subcostal long
      axis view at baseline, at 1 and 5 minutes after intrathecal injection, and
      immediately after delivery; the maximum and minimum IVC diameters were measured,
      and the IVC collapsibility index (CI) was calculated using the formula: IVC-CI =
      (maximum IVC diameter - minimum IVC diameter)/maximum IVC diameter. The primary
      outcome was the total ephedrine dose. RESULTS: Data from 198 patients (99
      patients in each group) were analyzed. The median (range) of the total ephedrine
      dose was 11 (0-60) mg in the combination group and 13 (0-61) mg in the
      crystalloid coload group; the median of the difference (95% nonparametric
      confidence interval) was -2 (-5 to 0.00005) mg, P = .22. There were no
      significant differences between the 2 groups in the number of patients requiring
      ephedrine, the incidence of hypotension and severe hypotension, the time to the
      first ephedrine dose, and neonatal Apgar scores at 1 and 5 minutes. The maximum
      and minimum IVC diameters in each group increased after spinal anesthesia and
      after delivery, and they were larger in the combination group. The IVC-CI after
      delivery was higher in the crystalloid coload group. CONCLUSIONS: The combination
      of 500-mL colloid preload and 500-mL crystalloid coload did not reduce the total
      ephedrine dose or improve other maternal outcomes compared with 1000-mL
      crystalloid coload. The IVC was reliably viewed before and during cesarean
      delivery, and its diameters significantly changed over time and differed between
      the 2 groups.

PMID- 29461393
TI  - Neuraxial Anesthesia in Children With Ventriculoperitoneal Shunts.
AB  - Neuraxial anesthesia has been demonstrated to be safe and effective for children
      undergoing subumbilical surgery. There is limited evidence regarding the safety
      of neuraxial anesthesia in pediatric patients with a ventriculoperitoneal shunt.
      We evaluated a series of 25 patients with indwelling ventriculoperitoneal shunts
      for complications within 30 days of any procedure performed with a neuraxial
      technique. One patient required a ventriculoperitoneal shunt revision 5 days
      after a lumbar catheter placement. The neurosurgeon determined the revision to be
      likely unrelated to the patient's lumbar catheter. Concerns about the use of
      neuraxial anesthesia in patients with an indwelling ventriculoperitoneal shunt
      may be overstated.

PMID- 29461394
TI  - Diagnosis and Management of Polytraumatized Patients With Severe Extremity
      Trauma.
AB  - Multiply injured patients with severe extremity trauma are at risk of acute
      systemic complications and are at high risk of developing longer term orthopaedic
      complications including soft-tissue infection, osteomyelitis, posttraumatic
      osteoarthritis, and nonunion. It is becoming increasingly recognized that injury
      magnitude and response to injury have major jurisdiction pertaining to patient
      outcomes and complications. The complexities of injury and injury response that
      affect outcomes present opportunities to apply precision approaches to understand
      and quantify injury magnitude and injury response on a patient-specific basis.
      Here, we present novel approaches to measure injury magnitude by adopting methods
      that quantify both mechanical and ischemic tissue injury specific to each
      patient. We also present evolving computational approaches that have provided new
      insight into the complexities of inflammation and immunologic response to injury
      specific to each patient. These precision approaches are on the forefront of
      understanding how to stratify individualized injury and injury response in an
      effort to optimize titrated orthopaedic surgical interventions, which invariably
      involve most of the multiply injured patients. Finally, we present novel methods
      directed at mangled limbs with severe soft-tissue injury that comprise severely
      injured patients. Specifically, methods being developed to treat mangled limbs
      with volumetric muscle loss have the potential to improve limb outcomes and also
      mitigate uncompensated inflammation that occurs in these patients.

PMID- 29461395
TI  - Critical-Size Bone Defects: Is There a Consensus for Diagnosis and Treatment?
AB  - There is a significant burden of disease associated with bone defects, and their
      management is challenging. These injuries have a profound clinical and economic
      impact, and outcomes are limited by high rates of complication and reoperation,
      as well as poor functional outcomes. There remains a lack of consensus around
      definitions, reliable models, and best practices for the surgical management of
      bone defects. The current state of the literature on bone defects is reviewed
      here, with a focus on defining critical-size bone defect, the use of the induced
      membrane technique, the role of biologics, and the management of infected bone
      defects.

PMID- 29461396
TI  - Absolute Versus Relative Fracture Fixation: Impact on Fracture Healing.
AB  - The goals of all orthopaedic surgeons treating fractures are, and will remain,
      obtaining union of the fracture with a well-aligned and functional limb while
      minimizing the risk of complications. This requires us to understand how the
      biomechanical environment of the fracture affects healing and to be able to
      discern which mechanical environment is preferred over another. Understanding the
      spectrum of stability imparted by our current surgical devices is paramount to
      giving our patients the best opportunity to heal and recover from their injury.
      Gone are the simplistic views of plates and screws being applied for absolute
      stability and nails and external fixators being applied for relative stability.
      This review sheds new light on how the use of different implants provides the
      appropriate stability to encourage fracture healing and limit the risk of
      complication and loss of function.

PMID- 29461397
TI  - Biomechanics-Hot Topics Part I.
AB  - This study summarizes presentations of a symposium on biomechanically related hot
      topics of the 2015 Basic Science Focus Forum. Each topic emphasizes a
      biomechanical challenge common to all 4 of these presentations: an ideal fixation
      technique should deliver ample stability and sufficient flexibility to prevent
      fixation failure and to restore normal function.

PMID- 29461398
TI  - What Is Important Besides Getting the Bone to Heal? Impact on Tissue Injury Other
      Than the Fracture.
AB  - Fracture surgeons do a great job of managing bone issues, but they may overlook
      the associated soft tissue injuries that play a significant role in the final
      outcome after musculoskeletal injury. The soft tissue reconstruction ladder can
      help guide reconstructive procedures based on the least complex procedure that
      allows the best chance of fracture healing. Muscle injury, volume loss, and
      deconditioning occur with traumatic injury and during the recovery phase.
      Neuromuscular stimulation, nutrition, and strength training are potential ways to
      aid in recovery. Complex periarticular knee injuries have a high rate of
      associated soft tissue injuries that may affect outcome if associated with knee
      instability. Identifying and addressing these injuries can increase the
      likelihood of a good outcome. Articular cartilage loss can make articular
      reconstruction impossible. Large fresh osteoarticular allografts can be a
      reconstructive option. Addressing all the damaged structures involved with a
      fracture may be the next step in improving patient outcomes.

PMID- 29461399
TI  - How Does Orthopaedic Research Affect Patient Care?
AB  - Academic medicine hinges on high-quality results from research. Surgeon
      scientists spend their career acquiring grants, writing papers, and educating a
      next generation of scientists. The real question is how well are we at playing
      this game? Does our research change surgical practice or affect patient care or
      government policy? Ideally, published research does and will continue to shape
      the way care is delivered. Key questions remain, however; what is the return on
      research investment in orthopaedics? How can surgeons decide which "evidence"
      matters, and does practice-change only refer to Level I evidence (randomized
      trials)? This review considers all these questions.

PMID- 29461400
TI  - Biomechanics-Hot Topics Part II.
AB  - Orthopaedic surgery and biomechanics are intimately partnered topics in medicine.
      Biomechanical principles are used to design implants and fashion treatment
      protocols. Although it would seem that biomechanical principles in the design of
      fixation devices and fracture repair constructs have been already finalized,
      there are several points of controversy remaining. New technology has raised new
      questions, while at the same time, we still do not fully understand simple
      clinical principles such as time of fracture healing depending on the construct
      used. This review looks at several of these current controversies to better
      understand what work is needed in fracture care going forward.

PMID- 29461401
TI  - Outside the Bone: What Is Happening Systemically to Influence Fracture Healing?
AB  - This article summarizes presentations of a symposium on bone health-related hot
      topics of the 2016 Basic Science Focus Forum. Taken together, these topics
      emphasize the critical importance of bone health in fracture management, the
      systemic factors that influence fracture healing, and the need to focus on issues
      other than simply the technical aspects of fracture repair.

PMID- 29461402
TI  - Management of Mangled Extremities and Orthopaedic War Injuries.
AB  - In 16 years of conflict, primarily in Iraq and Afghanistan, wounded warriors have
      primarily been subjected to blast type of injuries. Evacuation strategies have
      led to unprecedented survival rates in blast-injured soldiers, resulting in large
      numbers of wounded warriors with complex limb trauma. Bone and soft tissue
      defects have resulted in increased use of complex reconstructive algorithms to
      restore limbs and function. In addition, in failed salvage attempts, advances in
      amputation options are being developed. In this review, we summarize state-of-the
      art limb-salvage methods for both soft tissue and bone. In addition, we discuss
      advances in diagnostic methods with development of personalized clinical decision
      support tools designed to optimize outcomes after severe blast injuries. Finally,
      we present new advances in osteointegrated prostheses for above-knee amputations.

PMID- 29461403
TI  - Fracture Healing Adjuncts-The World's Perspective on What Works.
AB  - Treatment of bone defects remains a challenging clinical problem. Despite our
      better understanding of bone repair mechanisms and advances made in microsurgical
      techniques and regenerative medicine, the reintervention rates and morbidity
      remain high. Surgical techniques such as allograft implantation, free
      vascularized fibular graft, distraction osteogenesis, loaded titanium cages, and
      the induced membrane technique continue to evolve, but the outcome can be
      affected by a number of parameters including the age of the patient,
      comorbidities, systemic disorders, the location of the defect, and the surgeon's
      preference and experience. In the herein article, a brief summary of the most
      currently used techniques for the management of bone defects is presented.

PMID- 29461404
TI  - Use of Patient-Related Outcomes After Orthopaedic Trauma: Helpful or Not So Much?
AB  - Over 100 years ago, the orthopaedic surgeon, Ernest Codman, recommended that
      surgeons and hospitals be paid by the "end result." Healthcare Reform is moving
      to value over volume, and patient-reported outcomes (PROs) are 1 measure of
      quality and outcomes that are becoming pervasive. In this study, the current
      status of patient-reported outcomes and their use in orthopaedic trauma was
      reviewed. The contributors presented the state of PRO measurements at the Basic
      Science Focus Forum at the OTA Annual Meeting in 2016. Information on the
      currently available PROs was presented and analyzed to determine whether they
      were adequate for research in orthopaedic trauma. PROs were then discussed in the
      context of which were the most appropriate for determining outcomes in trauma
      surgery. The concept of mobility as a validated PRO for an assessment of general
      health was then presented. The final topic was a summary of how PROs will be used
      by insurers and governmental agencies. These topics provide a comprehensive
      overview of the current state of PROs in the context of orthopaedic trauma.

PMID- 29461405
TI  - Principles of Nonunion Management: State of the Art.
AB  - A substantial proportion of fractures can present with nonunion, and the
      management of nonunion continues to present a challenge for orthopaedic surgeons.
      A variety of biological, mechanical, patient, and injury factors can contribute
      to the occurrence of nonunion, and often the cause of nonunion may be
      multifactorial. Successful management often requires assessment and treatment of
      more than one of these factors. This article reviews common factors that may
      contribute to nonunion including infection, impaired biology, and metabolic
      disorders. In addition, new and evolving strategies for diagnosing the cause and
      effectively treating nonunion including the diagnosis of infection, metabolic
      workup, bone grafting, cell-based therapies, and biological adjuvants are
      reviewed and discussed.

PMID- 29461406
TI  - Interventional Procedures Outside of the Operating Room: Results From the
      National Anesthesia Clinical Outcomes Registry.
AB  - OBJECTIVES: This study examines the impact of procedural locations and types of
      anesthetics on patient outcomes in non-operating room anesthesia (NORA)
      locations. The National Anesthesia Clinical Outcomes Registry database was
      examined to compare OR to NORA anesthetic complications and patient demographics.
      METHODS: The National Anesthesia Clinical Outcomes Registry database was examined
      for all patient procedures from 2010 to 2013. A total of 12,252,846 cases were
      analyzed, with 205 practices contributing information, representing 1494
      facilities and 7767 physician providers. Cases were separated on the basis of
      procedure location, OR, or NORA. Subgroup analysis examined outcomes from
      specific subspecialties. RESULTS: NORA procedures were performed on a higher
      percentage of patients older than 50 years (61.92% versus 55.56%, P < 0.0001).
      Monitored anesthesia care (MAC) (20.15%) and sedation (2.05%) were more common in
      NORA locations. The most common minor complications were postoperative nausea and
      vomiting (1.06%), inadequate pain control (1.01%), and hemodynamic instability
      (0.62%). The most common major complications were serious hemodynamic instability
      (0.10%) and upgrade of care (0.10%). There was a greater incidence of
      complications in cardiology and radiology locations. Overall mortality was higher
      in OR versus NORA (0.04% versus 0.02%, P < 0.0001). Subcategory analysis showed
      increased incidence of death in cardiology and radiology locations (0.05%).
      CONCLUSIONS: NORA procedures have lower morbidity and mortality rates than OR
      procedures, contrary to some previously published studies. However, the increased
      complication rates in both the cardiology and radiology locations may need to be
      the target of future safety investigations. Providers must ensure proper
      monitoring of patients, and NORA locations need to be held to the same standard
      of care as the main operating room. Further studies need to identify at-risk
      patients and procedures that may predispose patients to complications.

PMID- 29461407
TI  - "The Jackson Table Is a Pain in the...": A Qualitative Study of Providers'
      Perception Toward a Spinal Surgery Table.
AB  - OBJECTIVE: The aim of this study was to define health care providers' perceptions
      toward prone patient positioning for spine surgery using the Jackson Table, which
      has not been hitherto explored. METHODS: We analyzed open-ended questionnaire
      data and interviews conducted with the spine surgical team regarding the current
      process of spinal positioning/repositioning using the Jackson Table. Participants
      were asked to provide an open-ended explanation as to whether they think the
      current process of spinal positioning/repositioning is safe for the staff or
      patients. Follow-up qualitative interviews were conducted with 11 of the
      participants to gain an in-depth understanding of the challenges and safety
      issues related to prone patient positioning. RESULTS: Data analysis resulted in 6
      main categories: general challenges with patient positioning, role-specific
      challenges, challenges with the Jackson Table and the "sandwich" mechanism,
      safety concerns for patients, safety concerns for the medical staff, and
      recommendations for best practices. CONCLUSIONS: This study is relevant to
      everyday practice for spinal surgical team members and advances our understanding
      of how surgical teams qualitatively view the current process of patient
      positioning for spinal surgery. Providers recommended best practices for using
      the Jackson Table, which can be achieved through standardized practice for
      transfer of patients, educational tools, and checklists for equipment before
      patient transfer and positioning. This research has identified several important
      practice opportunities for improving provider and patient safety in spine
      surgery.

PMID- 29461408
TI  - Brimonidine Ophthalmic Solution 0.025% for Reduction of Ocular Redness: A
      Randomized Clinical Trial.
AB  - SIGNIFICANCE: The alpha2-adrenergic receptor agonist brimonidine has been
      reported to induce conjunctival blanching in cataract, strabismus, laser
      refractive, and filtration procedures. Clinicians are often faced with red eyes
      with no apparent underlying pathology. Low-dose brimonidine reduced ocular
      redness in such subjects with efficacy maintained over 1 month and negligible
      rebound redness. PURPOSE: The aim of this study was to evaluate the safety and
      efficacy of brimonidine tartrate ophthalmic solution 0.025% for the treatment of
      ocular redness. METHODS: In this single-center, double-masked, phase 3 clinical
      trial, adult subjects with baseline redness of more than 1 unit in both eyes (0-
      to 4-unit scale) were randomized 2:1 to brimonidine 0.025% or vehicle. A single
      dose was administered in-office (day 1); thereafter subjects instilled treatment
      four times a day for 4 weeks, with clinic visits on days 15, 29, and 36 (7 days
      post-treatment). Efficacy end points included investigator-evaluated redness 5 to
      240 minutes post-instillation on day 1 (primary); investigator-evaluated change
      from baseline 1, 360, and 480 minutes post-instillation on day 1, and 1 and 5
      minutes post-instillation on days 15 and 29; total clearance of redness, and
      subject-assessed redness. Safety/tolerability measures included adverse events,
      rebound redness, and drop comfort. RESULTS: Sixty subjects were randomized (n =
      40 brimonidine, n = 20 vehicle). Investigator-assessed redness was lower with
      brimonidine versus vehicle over the 5- to 240-minute post-instillation period
      (mean [SE], 0.62 [0.076] vs. 1.49 [0.108]; P < .0001) and at each time point
      within that period (P < .0001). At 1, 360, and 480 minutes post-instillation,
      respectively, the mean differences (95% confidence interval) between treatments
      were -0.73 (-1.05 to -0.41), -0.57 (-0.84 to -0.29), and -0.39 (-0.67 to -0.10),
      respectively. No tachyphylaxis was evident with brimonidine on days 15 and 29,
      and minimal rebound redness was observed following discontinuation. Adverse
      events were infrequent, and brimonidine was rated as very comfortable.
      CONCLUSIONS: Brimonidine 0.025% appeared safe and effective for reduction of
      ocular redness, with an 8-hour duration of action, no evidence of tachyphylaxis,
      and negligible rebound redness.

PMID- 29461409
TI  - Repeatability of Monocular Acuity Testing in Adults with and without Down
      Syndrome.
AB  - PURPOSE: Individuals with Down syndrome may experience greater difficulty
      reliably performing visual acuity (VA) tests because of intellectual disability
      and limitations in visual quality. This study evaluated the repeatability of
      acuity (Bailey-Lovie [BL] and HOTV) in subjects with and without Down syndrome.
      METHODS: High-contrast VA was measured in both eyes of 30 subjects with Down
      syndrome (mean, 30 years; range, 18 to 50 years) and 24 control subjects without
      Down syndrome (mean, 29 years; range, 18 to 50 years). In the Down syndrome
      group, 23 subjects performed BL, and 7 subjects performed HOTV. All control
      subjects performed both BL and HOTV, but for HOTV analysis, only seven age
      matched control subjects were included. For each eye, subjects performed VA three
      times on different charts (computer controlled, single-line display) until five
      total letters were missed on each chart. A repeated-measure ANOVA was used to
      compare the acuity measures between groups. RESULTS: The average logMAR VA for
      subjects with Down syndrome was approximately six lines worse than the control
      subjects (BL: Down syndrome = right eye: 0.51 +/- 0.16, left eye: 0.53 +/- 0.18;
      control = right eye: -0.06 +/- 0.06, left eye: -0.06 +/- 0.08, P < .0001; HOTV:
      Down syndrome = right eye: 0.47 +/- 0.19, left eye: 0.46 +/- 0.16; control: right
      eye = -0.11 +/- 0.09, left eye: -0.07 +/- 0.07, P < .001). Bailey-Lovie VA
      repeatability (1.96 * Sw * ?2) was 0.13 logMAR (6.5 letters) for Down syndrome
      and 0.09 logMAR (4.5 letters) for control subjects. HOTV VA repeatability was
      0.16 logMAR (eight letters) for both Down syndrome and control subjects.
      CONCLUSIONS: Despite poorer acuity in individuals with Down syndrome,
      repeatability of VA measurements was comparable to control subjects for both BL
      and HOTV techniques.

PMID- 29461411
TI  - Sequencing effects of object control and locomotor skill during Integrated
      Neuromuscular Training in 6-7 year old children.
AB  - This study examined whether scheduling of object control (e.g., throwing,
      catching) and locomotor skills (e.g., running, jumping), within an integrated
      neuromuscular training (INT) program, results in different responses in motor
      competence, muscular fitness and perceived motor competence in 6-7 year old
      children. Seventy seven boys and 63 girls (n = 140) from 3 primary schools were
      randomised into three, 10-week interventions, Loco First (n = 50) where locomotor
      skills were performed first followed by object control skills; Object First (n
      =48) where object control skills were performed first followed by locomotor
      skills or a control group (n =42, CON) who undertook school Physical Education.
      Results indicated greater total motor competence in Loco First and Object First
      vs CON (P = 0.001) with the increases in motor competence being greater for
      Object First vs Loco First (P = 0.001). Sprint speed (10m) was lower for Object
      First vs CON (P = .024). Standing long jump distance was greater in Loco First vs
      CON (P .0001) and Object First (P = .0001). Seated medicine ball throw distance
      was greater for Loco First and Object First vs CON (Both P = .001). Perceived
      motor competence was also higher for Object First vs Loco First (P = .005) and
      CON (P = .001). This study suggests that scheduling object control skills before
      locomotor skills within school-based strength and conditioning has a greater
      effect on motor competence, muscular fitness and perceived motor competence in 6
      7 year old children.

PMID- 29461410
TI  - Impact of Cognitive Demand during Sustained Near Tasks in Children and Adults.
AB  - SIGNIFICANCE: These results demonstrate that accommodation in children is more
      accurate and less variable when performing a sustained near task with increased
      cognitive demand. In addition, children with increased uncorrected hyperopia have
      less stable accommodative responses, which may have visual implications during
      sustained near tasks. PURPOSE: This study investigated accommodative accuracy
      (lag) and variability during sustained viewing for passive and active tasks in
      children and adults with emmetropia and uncorrected hyperopia. METHODS: Lag and
      variability (root mean square [RMS] and low-frequency component) were measured in
      54 children aged 3 to younger than 10 years with mean spherical equivalent of
      +1.31 +/- 1.05 diopters (D) (range, -0.37 to +4.58 D) and 8 adults aged 22 to 32
      years with mean spherical equivalent +0.65 +/- 0.62 D (range, -0.13 to +1.15 D).
      Subjects viewed 20/50 stimuli at 33 cm during both a 10-minute passive and active
      task. Group 1 (<6 years or nonreaders) viewed shapes; group 2 (>=6 years and
      reading) and adults read passages. RESULTS: Groups 1 and 2 had larger lags, RMS,
      and low-frequency component for passive versus active tasks (P < .001). Lag and
      RMS did not differ between tasks in adults (P > .05), but low-frequency component
      was larger during passive viewing (P = .04). Group 1 had significantly higher RMS
      and low-frequency component than group 2 and the adults in the passive condition
      had greater low-frequency component in the active condition. In children,
      hyperopia was independently associated with RMS and low-frequency component under
      passive (RMS 95% confidence interval [CI], 0.04 to 0.15; low-frequency component
      95% CI, 0.00011 to 0.00065) and active (RMS 95% CI, 0.001 to 0.06; 95% CI,
      0.000014 to 0.00023) viewing. CONCLUSIONS: Accommodation is more accurate and
      less variable when children are engaged in the task. Children also have more
      variable accommodation than adults. In addition, children with greater hyperopia
      have more variable accommodation during sustained near tasks.

PMID- 29461412
TI  - The Effect of Augmented Feedback Type and Frequency on Velocity-Based Training
      Induced Adaptation and Retention.
AB  - The purpose of this study was to compare the benefits of 4-weeks of velocity
      based training (VBT) using different augmented feedback (AugFb) types and the
      frequency of AugFb, and whether adaptations are retained 10 days post-training.
      Thirty-seven collegiate male rugby players were divided into groups that received
      immediate-feedback (ImFb; n=9), visual-feedback (ViFb; n=10), average-feedback
      (AvgFb; n=10) and no-feedback (NoFb; n=8) during each VBT session consisting of 3
      sets of 5 repetitions of loaded jump squats. The ImFb group received AugFb
      regarding lifting velocity under loaded jump squats (LV-JS) following every jump,
      whereas LV-JS measures were averaged following each set of jumps and presented to
      the AvgFb group. The loaded jump squats were video-recorded and displayed as
      kinematic feedback for the ViFb group following each set, although no feedback
      was provided for the NoFb group. LV-JS measures were reported at baseline, during
      each training session and 10-days post training. LV-JS measures were
      significantly greater for the ImFb Group compared to the other groups during a
      number of post-baseline time points (P<0.05). Furthermore, at 4-weeks of VBT and
      10 days post-retention, effect size (ES) calculations showed that LV-JS measures
      were greater with moderate to large effects for the ImFb group compared to the
      NoFb (ES=1.02-1.25), AvgFb (ES=0.78-0.82) and ViFb (ES=0.74-1.60), respectively.
      However, LV-JS measures were reduced with moderate to large effects 10 days post
      retention for the ViFb (ES=-0.60) and NoFb (ES=-0.85) groups. Providing LV-JS
      feedback following each jump appears to optimize performance and should be
      considered as a training tool during VBT.

PMID- 29461413
TI  - Cardiac-Autonomic Responses to In-Season Training Among Division-1 College
      Football Players.
AB  - Despite having to endure a rigorous in-season training schedule, research
      evaluating daily physiological recovery status markers among American football
      players is limited. The purpose of this study was to determine if recovery of
      cardiac-autonomic activity to resting values occurs between consecutive-day, in
      season training sessions among college football players. Subjects (n = 29) were
      divided into groups based on position: receivers and defensive backs (SKILL, n =
      10); running backs, linebackers and tight-ends (MID-SKILL, n = 11) and linemen
      (LINEMEN, n = 8). Resting heart rate (RHR) and the natural logarithm of the root
      mean square of successive differences multiplied by twenty (LnRMSSD) were
      acquired at rest in the seated position prior to Tuesday and Wednesday training
      sessions and repeated over three weeks during the first month of the competitive
      season. A position * time interaction was observed for LnRMSSD (p = 0.04), but
      not for RHR (p = 0.33). No differences in LnRMSSD between days was observed for
      SKILL (Tuesday = 82.8 +/- 9.3, Wednesday = 81.9 +/- 8.7, p > 0.05). Small
      reductions in LnRMSSD were observed for MID-SKILL (Tuesday = 79.2 +/- 9.4,
      Wednesday = 76.2 +/- 9.5, p < 0.05) and LINEMEN (Tuesday = 79.4 +/- 10.5,
      Wednesday = 74.5 +/- 11.5, p < 0.05). The individually averaged changes in
      LnRMSSD from Tuesday to Wednesday were related to PlayerLoad (r = 0.46, p = 0.02)
      and body mass (r = -0.39, p = 0.04). Cardiac-parasympathetic activity did not
      return to resting values for LINEMEN or MID-SKILL prior to the next training
      session. Larger reductions in LnRMSSD tended to occur in players with greater
      body mass despite having performed lower workloads, though some individual
      variability was observed. These findings may have implications for how coaches
      and support staff address training and recovery interventions for players
      demonstrating inadequate cardiovascular recovery between sessions.

PMID- 29461414
TI  - Validity and Reliability of an on-Court Fitness Test for Assessing and Monitoring
      Aerobic Fitness in Squash.
AB  - Current on-court assessments of aerobic fitness in squash are not designed to
      yield a wealth of physiological data. Moreover, tests may require complex
      computer equipment or involve simulated racket strokes, which are difficult to
      standardize at high intensities. This study investigated the validity and
      reliability of a squash-specific fitness test which can yield both a standalone
      performance score, as well as pertinent physiological markers such as V[Combining
      Dot Above]O2max, the lactate turnpoint and oxygen cost, in a sport-specific
      environment. Eight national squash players completed three tests in a counter
      balanced order; an incremental laboratory treadmill test (LAB) and two on-court
      fitness tests (ST) that involved repeated shuttle runs at increasing speeds.
      V[Combining Dot Above]O2max during ST was agreeable with LAB (Typical error
      [TE]=3.3 mL.kg.min, r=0.79). The mean bias between LAB and ST was 2.5 mL.kg.min.
      There were no differences in maximum heart rate, post exercise blood lactate
      concentration or end of test RPE between LAB and ST (p>0.05). The ST was highly
      reliable, with 74 (10) laps completed in ST1 and 75 (12) laps in ST2 (mean bias=1
      lap, TE=3 laps, r=0.97). Physiological markers were also reliable, including
      V[Combining Dot Above]O2max, (TE=1.5 mL.kg.min, r=0.95), the lap number at 4 mMol
      (TE=4 laps, r=0.77) and average VO2 across the first 4 stages (TE=0.94 mL.kg.min,
      r=0.95). We observed good agreement between LAB and ST for assessing V[Combining
      Dot Above]O2max and between both on-court trials for assessing test performance
      and selected physiological markers. Consequently, we recommend this test for
      monitoring training adaptations and prescribing individualized training in elite
      squash players.

PMID- 29461415
TI  - The Relationship Between Maximal Aerobic Power and Recovery in Elite Ice Hockey
      Players During a Simulated Game.
AB  - This project investigated whether there was a relationship between maximal
      aerobic power and the recovery or performance in elite ice hockey players during
      a simulated hockey game. An on-ice protocol was used to simulate a game of ice
      hockey. Recovery values were determined by the differences in lactate and heart
      rate measures. Total distance traveled was also recorded as a performance
      measure. On two other days, subjects returned and completed a maximal aerobic
      power test on a treadmill and a maximal lactate test on ice. Statistical analysis
      showed no relationship between maximal aerobic power or maximal lactate values
      and recovery (heart rate, lactate) or the performance measure of distance
      traveled. It was concluded there was no relationship between maximal aerobic
      power and recovery during a simulated game in elite hockey players.

PMID- 29461416
TI  - Relationship Between Physiologic Tests, Body Composition Changes, and On-Ice
      Playing Time in Canadian Collegiate Hockey Players.
AB  - Delisle-Houde, P, Chiarlitti, NA, Reid, RER, and Andersen, RE. Relationship
      between physiologic tests, body composition changes, and on-ice playing time in
      canadian collegiate hockey players. J Strength Cond Res 32(5): 1297-1302, 2018
      Hockey player's body composition and physical fitness are suggested to influence
      coaching decisions regarding on-ice playing time. The purpose of this study was
      to explore the relationship between seasonal body composition changes, off-ice
      preseason testing, and on-ice metrics. Twenty-one Canadian collegiate hockey
      players (22.70 +/- 1.30 years old, 181.0 +/- 5.92 cm, 86.52 +/- 6.41 kg)
      underwent off-ice physical testing at the beginning of their season and had one
      total body dual energy x-ray absorptiometry scan at the beginning and end of the
      season. The team's statistician tracked all on-ice metrics. Pearson correlations
      were used to explore relationships between off-ice tests (long jump, vertical
      jump, beep test, and Wingate test), change in body composition (body fat
      percentage, visceral adiposity, and total lean tissue mass), and on-ice
      performance (average time on ice, average shift length, power play time, penalty
      kill time, and shot differential). Long jump was correlated with shot
      differential (r = -0.532, p <= 0.05) and average shift length (r = -0.491, p <=
      0.05) while fatigue index was correlated with average ice time (r = -0.476, p <=
      0.05). Hockey performance is a complex interaction of player's body compositions
      and skeletal fitness that interact to affect on-ice playing metrics.

PMID- 29461417
TI  - Strength Testing Following Anterior Cruciate Ligament Reconstruction. A
      Prospective Cohort Study Investigating Overlap of Tests.
AB  - The purpose of the present study was to determine whether overlap (redundancy)
      exists between individual tests in a comprehensive strength testing protocol used
      after anterior cruciate ligament (ACL) reconstruction surgery. If overlap is
      present, one or more components of the protocol could potentially be omitted to
      make the testing protocol more efficient, but without compromising the usefulness
      of the testing.Sixty-nine patients (46M, 23F; mean age 28Y) were strength tested
      at 6 and 12 months after ACL reconstruction as part of a prospective cohort
      study. The following knee flexor and extensor strength tests were performed:
      isokinetic concentric strength at 60 degrees /s and 180 degrees /s, isokinetic
      eccentric strength at 60 degrees /s, and isometric knee flexor strength at 60
      degrees  flexion. Peak and average torque values were extracted and the ratio
      between the operated and non-operated limb calculated as a limb symmetry index.
      Overlap of strength tests was investigated by fitting a linear regression model
      to the data with an R threshold of 0.56 used as an indication of overlap.Overlap
      between peak and mean torque was present for extensor and flexor concentric and
      eccentric measurements at 12 months and for concentric measurements at 6 months.
      Peak torque measurements were therefore used for subsequent analysis. Concentric
      extensor peak torque at 60 degrees /s and 180 degrees /s showed overlap at 6
      months (R = 0.73) but not at 12 months (R = 0.37). No other overlap was
      identified.In conclusion, there is little room for omission of individual
      strength testing protocol components due to the lack of overlap between tests.
      Isometric, eccentric and concentric tests may all provide unique information and
      all therefore should be considered for inclusion.

PMID- 29461418
TI  - Influence of biological maturity on the match performance of 8 to 16 year old
      elite male youth soccer players.
AB  - The aim of this study was to examine the influence of biological maturity on
      match performance in elite youth male soccer players. The participants were 80
      Premier League Academy outfield players (8-16 years old). Biological maturity was
      determined by calculating estimated chronological age at peak height velocity.
      The U9 and U10 squads played 6-a-side and the U11-U16 squads played 11-a-side
      inter-academy matches. All matches were analyzed using a 1 Hz Global Positioning
      System (SPI elite, GPSport, Australia) with squad specific speed zones which were
      calculated based on 5 m flying sprint speed in the last 5 m of 10 m sprint test.
      In the U9/U10s, earlier maturers were given a longer pitch time by coaches (~4
      min per match, p = 0.029) and covered a greater total distance (~9%, ~400 m, p =
      0.037) and a greater distance by walking (~13%, ~100 m, p = 0.024) and jogging
      (~12%, ~200 m, p = 0.014) during a match compared to later maturers. In the
      U13/U14s, earlier maturers covered a greater distance per hour of a match by high
      speed running compared to later maturers (~25%, ~130 m, p = 0.028) and spent a
      longer percentage of time in high speed running during a match compared to later
      maturers (3.4% vs. 2.7%, p = 0.034). Thus, coaches should take care to provide
      all players with a similar pitch-time and should be aware in the talent
      identification and development process, particularly with the U13/U14 age group,
      that maturity can influence high speed match running performance.

PMID- 29461419
TI  - Morphological and physical fitness profile of young female sprint kayakers.
AB  - Traditionally, physical and anthropometrical profiles of the most successful
      kayak athletes have been identified in male kayakers. This study attempted to
      identify the differences in morphology and fitness level of two performance-based
      groups of young elite female paddlers. Eighty-six female kayakers, aged 13.62 +/-
      0.57 years (mean +/- SD) were allocated in two groups (Top-10 and Rest) depending
      on their ranking in the three Olympic distances (200, 500 and 1000 meters). All
      subjects underwent a battery of anthropometrical (heights, weight, girths and sum
      of skinfolds), physical fitness (overhead medicine ball throw, countermovement
      jump, sit-and-reach test and 20-m multistage shuttle run test) and specific
      performance assessments (200, 500 and 1000 meters). Best paddlers presented
      significantly greater anthropometrical values in muscle mass percentage, maturity
      status and chronological age (p < 0.05) whereas physical fitness comparison only
      revealed significant differences in countermovement jump (p < 0.05). Furthermore,
      aerobic power and muscle mass percentage appear to be crucial in achieving
      optimal performances at long (1000-m) and short duration races (200 and 500-m).
      These findings confirm the importance of a larger and compact morphology, as well
      as superior fitness level, for success in female kayakers. The current results
      not only identify the weak areas on body composition and physical fitness
      depending on the maturity status but also the development of specific training
      programs for FEMALES.

PMID- 29461420
TI  - The effect of ibuprofen on muscle, hematological and renal function, hydric
      balance, pain, and performance during intense long-distance running.
AB  - The aim of this study was to investigate the effect of prophylactic use of
      nonsteroidal anti-inflammatory drugs (NSAID, i.e. Ibuprofen) on physical
      performance, vertical jump, muscle biomarkers, liver, kidney, acute pain and
      hydration status of participants in the 42 km Trail Running Challenge, a long
      distance race integrated over mountain routes. The sample consisted of 20 males
      randomly divided into two groups: a control group (CG) and an experimental group
      (EG) with 12 completing the race (41.1+/-8.8 y; 75.7+/-12.1 kg) and included in
      the final analysis. The EG were administered an ibuprofen capsule (400 mg)
      fifteen minutes before the beginning of the race, and again after 5 hours of
      racing if the route was not yet complete. There were significant time main
      effects for creatine kinase (CK) (p=0.001; f Cohen=0.25), lactate dehydrogenase
      (LDH) (p<0.001; f Cohen=2.05), aspartate aminotransferase (AST) (p=0.002; f
      Cohen=1.53), creatinine (p=0.002; f Cohen=2.24), urea (p=0.001; f Cohen=2.25),
      heart rate (HR) (p<0.001; f Cohen=4.88) and pain scores (p<0.001; f Cohen=1.93)
      which all increased during the race. There was a group * time interaction for
      squat jump (SJ) which significantly decreased in only the CG (p= 0.045; f
      Cohen=2.17). This may have been related to increased frequency of pain reported
      after the race in the gastrocnemius of the CG compared to the EG (p<0.05). It was
      concluded that ibuprofen intake did not reduce muscle damage during the
      competition but maintained leg muscular power performance (i.e. vertical jump),
      possibly by reducing gastrocnemius muscle pain.

PMID- 29461421
TI  - Tethered Swimming Test: Reliability and the Association to Swimming Performance
      and Land-based Anaerobic Performance.
AB  - The purpose of this study was three-fold: (a) to examine the test-retest
      reliability of a 30 second maximal tethered freestyle swimming test (TST), (b) to
      assess the validity of the TST by examining the association to sprint swimming
      performance and, (c) to examine the associations between a swim-specific and land
      based measure of anaerobic performance. A total of twenty-nine male and female
      swimmers were recruited to participate in the study. Each participant completed a
      Wingate Anaerobic cycling test (WAnT), two or four TST, and a 22.9 meter (25
      yard), 45.7 meter (50 yard), and 91.4 meter (100 yard) maximal freestyle
      performance swims (PS). Mean and peak force (Fmean, Fpeak) were recorded for both
      the WAnT and TST, and average swimming velocity and time were recorded for the
      PS. Additionally, physiological and perceptual measures were recorded immediate
      post exercise for all tests. The results of the present investigation showed
      strong intersession and intrasession reliability (R= 0.821-0.975; p<0.001) for
      force parameters of the TST. Moderate correlations were found between Fmean and
      PS time and velocity of all distances, with slightly weaker correlations between
      Fpeak and the 22.9 meter (time and velocity) and 45.7 meter (velocity) PS.
      Finally, moderate correlations were found for Fmean and Fpeak of the TST and
      WAnT. This study demonstrated that the TST is a reliable measure, with moderate
      association to swimming performance, producing similar physiological responses
      compared to free swimming. Therefore, future research shoulSd focus on
      investigating the potential benefits of utilizing the TST as a regular assessment
      tool as a part of a competitive swimming training program to track adaptations
      and inform training decisions.

PMID- 29461422
TI  - Eight Weeks of Strength and Power Training Improves Club Head Speed in Collegiate
      Golfers.
AB  - Club head speed (CHS) is a major determinant of drive distance, a key component
      of golf performance. The purpose of this study was to determine the indirect
      effects of an eight-week strength and power program on CHS. Twelve (6 male, 6
      female) NCAA Division II golfers (20.3+/-1.5 years) randomly assigned to an
      intervention or control group, underwent either a periodized strength and power
      program consisting of high-load barbell movements or a bodyweight and rotational
      movement focused resistance training program. Outcomes were CHS, countermovement
      jump (CMJ) height, and 1RM back squat (BS), power clean (PC), and deadlift (DL).
      Dependent t-tests were utilized to assess differences in outcome variables pre-to
      post for each group, independent t-tests were utilized to assess differences
      between groups, and Pearson correlations were utilized to assess associations
      between CHS and outcome variables. On average, the intervention group experienced
      improvements in all outcome variables except peak CHS (p=0.60); the control group
      displayed no changes in any outcome variable except a decrease in average CHS
      (p=0.028). Compared to the control group, the intervention group experienced
      greater improvements in average CHS, BS, PC, and average and peak CMJ height
      (p<0.05). Additionally, CHS had large associations with PC (r=0.70, p=0.012), BS
      (r=0.64, p=0.025), DL (r=0.54, p=0.068) and CMJ (r=0.73, p=0.007). These results
      suggest improving muscular strength and power by increasing PC, BS, and CMJ is
      associated with increased CHS in collegiate golfers. Integrating a high-load,
      barbell-focused strength and power program may be beneficial for improving CHS
      and indirectly, golf performance.

PMID- 29461423
TI  - The effect of short and long term aerobic training years on systemic O2
      utilization, and muscle and prefrontal cortex tissue oxygen extraction in young
      women.
AB  - This study aimed to determine if systemic O2 utilization (V[Combining Dot
      Above]O2) and tissue oxygen extraction (deoxyhemoglobin [HHb]) in the vastus
      lateralis (VL), gastrocnemius (GAST) and pre-frontal cortex (PFC) were different
      during exercise between short-term trained (STT 6 - 24 months) and long-term
      trained (LTT > 5 yr) young women while controlling for current training load.
      Thirteen STT and 13 LTT participants completed ramp incremental (RI) and square
      wave constant load (SWCL) tests on a cycle ergometer. In LTT compared to STT: (i)
      V[Combining Dot Above]O2 was higher during the RI (p = 0.024) and SWCL (p =
      0.001) tests; (ii) HHb in the VL (p = 0.044) and GAST (p = 0.027) was higher in
      the RI test; and (iii) there were significant group x intensity interactions for
      V[Combining Dot Above]O2 in the SWCL test. The additional years of aerobic
      training in LTT compared to STT (LTT 7.1 +/- 1.9 vs STT 1.5 +/- 0.4 yr) resulted
      in higher V[Combining Dot Above]O2, and HHb in the VL and GAST. These results
      indicate that in young women, independent of current training load, systemic
      V[Combining Dot Above]O2 and peripheral muscle O2 extraction during exercise
      continues to increase beyond 24 months of aerobic training.

PMID- 29461424
TI  - Developmental disorders special issue: biomarkers and targeted therapeutics.

PMID- 29461425
TI  - Antibodies and the brain: antiribosomal P protein antibody and the clinical
      effects in patients with systemic lupus erythematosus.
AB  - PURPOSE OF REVIEW: Analysis of antiribosomal P protein autoantibodies (anti-P)
      pathogenicity in diffuse brain manifestations of neuropsychiatric lupus,
      emphasizing cognitive dysfunction and the recently emerged role of cross-reacting
      neuronal surface P antigen (NSPA) in alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid and N-Methyl-D-Aspartate receptor glutamatergic
      transmission. RECENT FINDINGS: Circulating anti-P antibodies associate with
      executive planning dysfunction and attention impairments in lupus patients and
      perturb glutamatergic transmission through NSPA in mice hippocampus, translating
      into impaired synaptic plasticity and spatial memory. Planning impairment impacts
      quality of life. SUMMARY: In addition to the known association with lupus
      psychosis, new clinical and experimental evidence reveal a pathogenic role of
      anti-P antibodies in cognitive dysfunction, mechanistically explained by the anti
      P interaction with NSPA as a target involved in glutamatergic synaptic
      plasticity.

PMID- 29461426
TI  - Emergent management of primary headache: a review of current literature.
AB  - PURPOSE OF REVIEW: The current article reviews recent data on treatment of acute
      headache patients in the acute care setting. RECENT FINDINGS: Intravenous fluid
      hydration, a common component of emergency department (ED) migraine therapy, does
      not improve pain outcomes and leads to longer ED lengths of stay. Therefore,
      intravenous fluids should be administered only to migraine patients with clinical
      evidence of dehydration. Similarly, intravenous ketamine has garnered interest as
      a treatment for acute pain but does not provide substantial relief to migraine
      patients. New studies on the serotonin (5-HT3; 5-hydroxytryptamine-3) antagonist
      granisetron, intranasal lidocaine, and high-flow oxygen have reported conflicting
      results for migraine patients. Finally, although experts recommend avoiding
      opioids in migraine treatment, opioid administration remains prevalent in the ED.
      A new study has demonstrated that patients who receive intravenous hydromorphone
      in the ED are much less likely to attain acute headache relief. Standardized
      headache protocols may decrease opioid use and provide significant pain relief
      for patients. SUMMARY: Recent data have clarified the role of opioids and
      ketamine in the ED (do not use!). The role of treatment protocols and intravenous
      fluids is still ill-defined. Subpopulations of migraine patients may benefit from
      high-flow oxygen and intranasal lidocaine.

PMID- 29461427
TI  - Educational Effectiveness of an Easily Made New Simulator Model for Ultrasound
      Guided Vascular Access and Foreign Body Management Procedures on Pediatric
      Patients.
AB  - OBJECTIVES: This study aimed to introduce an easily made chicken breast simulator
      for ultrasound (US)-guided vascular access, foreign body (FB) detection, and
      hydrodissection in pediatric patients and to validate the effectiveness for
      training using this phantom tissue model. METHODS: The authors made the tissue
      phantom simulator using a chicken breast and rubber tourniquet for vascular
      access and fragments of a tongue blade and steel clip for FB detection and
      hydrodissection using a very simple method. We provided training on US-guided
      vascular access (following the tip [FTT] method), FB detection, and
      hydrodissection using this model for novice physicians to learn US-guided
      procedures for pediatric patients. In addition, we provided a questionnaire to
      solicit their thoughts on their knowledge and confidence to perform these
      procedures before and after training and to learn their thoughts on the
      similarity to actual patients and usefulness of this model on a 10-point Likert
      scale. RESULTS: A total of 16 emergency residents participated in this study. We
      obtained US images during vascular access (FTT) and FB detection/ hydrodissection
      procedures using this phantom tissue model. Residents' knowledge of and
      confidence to perform US-guided FTT method and FB detection/hydrodissection
      procedures after training increased to a statistically significant degree (P <
      0.001 in all items). The median Likert scores regarding the similarity to actual
      patients and usefulness of this model were 8.5 (interquartile range, 7.5-9) and
      10 (interquartile range, 8-10), respectively. CONCLUSIONS: The model for US
      guided procedures used in this study can be constructed by simple and easy
      methods, presents realistic procedural images, and was useful for training novice
      physicians to conduct US-guided procedures on pediatric patients.

PMID- 29461428
TI  - Cervical Spine Imaging and Injuries in Young Children With Non-Motor Vehicle
      Crash-Associated Traumatic Brain Injury.
AB  - OBJECTIVES: The aim of this study was to evaluate cervical magnetic resonance
      imaging (MRI) and computed tomography (CT) practices and cervical spine injuries
      among young children with non-motor vehicle crash (MVC)-associated traumatic
      brain injury (TBI). METHODS: We performed a retrospective study of a stratified,
      systematic random sample of 328 children younger than 2 years with non-MVC
      associated TBI at 4 urban children's hospitals from 2008 to 2012. We defined TBI
      etiology as accidental, indeterminate, or abuse. We reported the proportion, by
      etiology, who underwent cervical MRI or CT, and had cervical abnormalities
      identified. RESULTS: Of children with non-MVC-associated TBI, 39.4% had abusive
      head trauma (AHT), 52.2% had accidental TBI, and in 8.4% the etiology was
      indeterminate. Advanced cervical imaging (CT and/or MRI) was obtained in 19.1% of
      all children with TBI, with 9.3% undergoing MRI and 11.7% undergoing CT. Cervical
      MRI or CT was performed in 30.9% of children with AHT, in 11.7% of accidental
      TBI, and in 10.7% of indeterminate-cause TBI. Among children imaged by MRI or CT,
      abnormal cervical findings were found in 22.1%, including 31.3% of children with
      AHT, 7.1% of children with accidental TBI, and 0% of children with indeterminate
      cause TBI. Children with more severe head injuries who underwent cervical imaging
      were more likely to have cervical injuries. CONCLUSIONS: Abusive head trauma
      victims appear to be at increased risk of cervical injuries. Prospective studies
      are needed to define the risk of cervical injury in children with TBI concerning
      for AHT and to inform development of imaging guidelines.

PMID- 29461429
TI  - Hospital Variation in Risk-Adjusted Pediatric Sepsis Mortality.
AB  - OBJECTIVES: With continued attention to pediatric sepsis at both the clinical and
      policy levels, it is important to understand the quality of hospitals in terms of
      their pediatric sepsis mortality. We sought to develop a method to evaluate
      hospital pediatric sepsis performance using 30-day risk-adjusted mortality and to
      assess hospital variation in risk-adjusted sepsis mortality in a large state-wide
      sample. DESIGN: Retrospective cohort study using administrative claims data.
      SETTINGS: Acute care hospitals in the state of Pennsylvania from 2011 to 2013.
      PATIENTS: Patients between the ages of 0-19 years admitted to a hospital with
      sepsis defined using validated International Classification of Diseases, Ninth
      revision, Clinical Modification, diagnosis and procedure codes. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: During the study period, there were 9,013
      pediatric sepsis encounters in 153 hospitals. After excluding repeat visits and
      hospitals with annual patient volumes too small to reliably assess hospital
      performance, there were 6,468 unique encounters in 24 hospitals. The overall
      unadjusted mortality rate was 6.5% (range across all hospitals: 1.5-11.9%). The
      median number of pediatric sepsis cases per hospital was 67 (range across all
      hospitals: 30-1,858). A hierarchical logistic regression model for 30-day risk
      adjusted mortality controlling for patient age, gender, emergency department
      admission, infection source, presence of organ dysfunction at admission, and
      presence of chronic complex conditions showed good discrimination (C-statistic =
      0.80) and calibration (slope and intercept of calibration plot: 0.95 and -0.01,
      respectively). The hospital-specific risk-adjusted mortality rates calculated
      from this model varied minimally, ranging from 6.0% to 7.4%. CONCLUSIONS:
      Although a risk-adjustment model for 30-day pediatric sepsis mortality had good
      performance characteristics, the use of risk-adjusted mortality rates as a
      hospital quality measure in pediatric sepsis is not useful due to the low volume
      of cases at most hospitals. Novel metrics to evaluate the quality of pediatric
      sepsis care are needed.

PMID- 29461430
TI  - Quantitative Imaging and Imaging Biomarkers: The Search for Generalizability in
      Radiology.

PMID- 29461431
TI  - Some Assembly Required.

PMID- 29461432
TI  - Teaching Through Storytelling: Narrative Nursing.

PMID- 29461433
TI  - What Is the Value of Nurse Educator Certification? A Comparison Study of
      Certified and Noncertified Nurse Educators.
AB  - AIM: The purpose of this study was to examine differences in how certified nurse
      educators and noncertified nurse educators valued nurse educator certification.
      BACKGROUND: No studies have investigated the differences in perceptions of
      certified and noncertified nurse educators. Understanding these differences may
      influence how the nursing profession recognizes and promotes excellence within
      the academic nursing specialty. METHOD: Perceived Value of Certification Tool
      Nurse Educator and demographic survey were administered via a web-based survey to
      a national sample of nursing faculty. RESULTS: Certified nurse educators valued
      certification with greater agreement than noncertified nurse educators. Personal
      accomplishment, personal satisfaction, and validation of knowledge were
      identified as the greatest rewards to certification. CONCLUSION: Nurse educators
      identified with intrinsic rewards of certification. Despite overall positive
      perceptions of nurse educator certification, strategies focused on extrinsic
      rewards may be necessary to increase certification rates. Such strategies may
      help overcome factors preventing educators from attaining certification.

PMID- 29461434
TI  - The Nursing Dean Role: An Integrative Review.
AB  - AIM: The aim of this integrative review was to appraise research on the
      uniqueness of the nursing dean role. BACKGROUND: Deans of nursing are challenged
      with multiple expectations of their role, which is unlike that of other deans in
      academia. Investigation is needed to understand what is entailed in being a dean
      of nursing. METHOD: This integrative review explores the role of the nurse dean
      utilizing a model described by Whittemore and Knafl. Their strategy uses a five
      step process of problem identification, literature search, data evaluation, data
      analysis, and presentation. RESULTS: Nursing deans are expected to excel in areas
      of education, the health care system, and relationships with the community
      stakeholders while navigating challenges of limited funding and a nationwide
      faculty shortage. CONCLUSION: This integrative literature review was an initial
      step toward the collective understanding of the nursing dean role.

PMID- 29461435
TI  - Types of Faculty Incivility as Viewed by Students in Bachelor of Science in
      Nursing Programs.
AB  - BACKGROUND: Faculty incivility can negatively affect student learning outcomes
      and safe clinical performance, yet little is known about the types of faculty
      incivility experienced by students. AIM: The aim of this qualitative descriptive
      study was to describe common types of incidents of faculty incivility as reported
      by students enrolled in traditional bachelor of science in nursing programs.
      MEHTOD: Qualitative descriptive methods were used to analyze the narratives of 30
      students who had experienced incidents of faculty incivility. RESULTS: A typology
      explicating the different ways students perceive faculty to be uncivil included
      six categories: judging or labeling students, impeding student progress, picking
      on students, putting students on the spot, withholding instruction, and forcing
      students into no-win situations. CONCLUSION: Nursing faculty and administrators
      can use the incident typology to guide discussions related to detecting,
      assessing, and preventing incivility in nursing education.

PMID- 29461436
TI  - Student and Faculty Views of Technology and Academic Success.

PMID- 29461437
TI  - NLN Partners With QSEN to Conduct a National Faculty Survey: Results Shed Light
      on State of QSEN Integration in Prelicensure Nursing Programs.

PMID- 29461438
TI  - Types of Faculty Incivility as Viewed by Students in Bachelor of Science in
      Nursing Programs.

PMID- 29461440
TI  - Ganja, No Barrier for Liver Transplantation?

PMID- 29461441
TI  - Sensing Danger After Kidney Transplantation.

PMID- 29461439
TI  - Investigating the Relationship Between Self-Directed Learning Readiness and Time
      Management Skills in Turkish Undergraduate Nursing Students.
AB  - AIM: The aims of this study were to determine self-directed learning and time
      management skills of undergraduate nursing students and to investigate the
      relationship between the concepts. BACKGROUND: The use of self-directed learning
      has increased as an educational strategy in recent years. METHOD: This
      descriptive and correlational study was conducted with 383 undergraduate nursing
      students in Turkey. Data were collected using a sociodemographic questionnaire,
      the Self-Directed Learning Readiness Scale, and Time Management Questionnaire.
      RESULTS: Mean scores were as follows: self-directed learning readiness, 159.12
      (SD = 20.8); time management, 87.75 (SD = 12.1). A moderate positive correlation
      was found between self-directed learning readiness and time management values.
      Time management scores were 78.42 when self-directed learning readiness was <=149
      and 90.82 when self-directed learning readiness was >= 150, with a statistically
      significant difference (p = .000). CONCLUSION: Level of self-directed learning
      and academic achievement were higher in students who managed their time well.

PMID- 29461442
TI  - 3D Endoscopic Donor Nephrectomy Versus Robot-assisted Donor Nephrectomy: A
      Detailed Comparison of 2 Prospective Cohorts.
AB  - BACKGROUND: There are 2 endoscopic surgical techniques that implement 3
      dimensional (3D) vision to overcome visual misperception: 3D endoscopy and the da
      Vinci surgical system. 3D endoscopy has several advantages, such as the presence
      of tactile feedback and easy implementation, at lower costs. We aimed to assess
      whether 3D endoscopy could be an alternative to the robot during living donor
      nephrectomy. METHODS: Between April 2015 and April 2016, we prospectively
      collected data on 40 patients undergoing 3D endoscopic living donor nephrectomies
      in 1 center, performed by a da Vinci-certified surgeon. Data on donors'
      perioperative results and recipient and graft survival were collected. These data
      were compared to 40 robot-assisted donor nephrectomies performed in the same
      center (between January 2012 and May 2014). RESULTS: Baseline characteristics for
      both groups were comparable. Intraoperative results showed a significantly
      shorter median skin-to-skin time of 138.5 minutes (125.8-163.8) versus 169.0
      (141.5-209.8) minutes in favor of the 3D group (P = 0.001). Warm ischemia time (P
      = 0.003) and hilar phase for both single (1 artery and vein) and multiple
      anatomies (>=1 artery and/or vein [P = 0.002 and P = 0.010, respectively]) were
      also significantly reduced in favor of the 3D group, with a flat learning curve.
      Follow-up demonstrated no readmissions nor significant differences for donors,
      recipients, and graft survival. CONCLUSIONS: 3D endoscopy may be a good
      alternative to robot-assisted donor nephrectomy because morbidity, graft, and
      recipient survival were comparable, with a significantly shorter median skin-to
      skin time, warm ischemia time, and hilar dissection phase. Furthermore,
      implementation was easy and at lower costs, whereas tactile feedback was
      preserved.

PMID- 29461444
TI  - The Effect of Ecmo on the New Vancomycin Dosing Regimen in Critically Ill
      Patients Receiving Continuous Veno-Venous Hemofiltration.
AB  - BACKGROUND: The optimal dosing regimen of vancomycin for critically ill patients
      receiving continuous veno-venous hemofiltration (CVVH) remains controversial, not
      to mention those with concurrent use of extracorporeal membrane oxygenation
      (ECMO). We aimed to determine if a new dosing regimen can achieve the target
      vancomycin trough concentration (Ctrough) of 10-20 MUg/mL in patients receiving
      CVVH with or without ECMO. METHODS: We conducted a retrospective study by
      enrolling patients who received vancomycin while undergoing CVVH. The vancomycin
      dosing regimen was 15-20 mg/kg as the loading dose and 7.5 mg/kg every 12 h as
      the maintenance doses. Serum concentration was determined after at least four
      doses of vancomycin were given. RESULTS: A total of 38 patients were enrolled, of
      which 21 were also on ECMO. The ultrafiltration rate of CVVH was 30.6 +/- 5.5
      mL/kg/h with the Ctrough of 14.7 +/- 3.5 MUg/mL. Ctrough was within the target
      range in 82% of patients. All CVVH-only patients achieved the target
      concentration, while only 76.2% of those with concurrent ECMO did (p = 0.031).
      CONCLUSIONS: All patients receiving CVVH achieved the target Ctrough with this
      new dosing regimen, but those with concurrent ECMO did not. Ctrough must be more
      closely monitored in patients using ECMO simultaneously.

PMID- 29461443
TI  - Evaluation of Multiple Linear Regression-Based Limited Sampling Strategies for
      Enteric-Coated Mycophenolate Sodium in Adult Kidney Transplant Recipients.
AB  - BACKGROUND: Although multiple linear regression-based limited sampling strategies
      (LSSs) have been published for enteric-coated mycophenolate sodium, none have
      been evaluated for the prediction of subsequent mycophenolic acid (MPA) exposure.
      This study aimed to examine the predictive performance of the published LSS for
      the estimation of future MPA area under the concentration-time curve from 0 to 12
      hours (AUC0-12) in renal transplant recipients. METHODS: Total MPA plasma
      concentrations were measured in 20 adult renal transplant patients on 2 occasions
      a week apart. All subjects received concomitant tacrolimus and were approximately
      1 month after transplant. Samples were taken at 0, 0.33, 0.5, 1, 1.5, 2, 2.5, 3,
      3.5, 4, 6, and 8 hours and 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 9, and
      12 hours after dose on the first and second sampling occasion, respectively.
      Predicted MPA AUC0-12 was calculated using 19 published LSSs and data from the
      first or second sampling occasion for each patient and compared with the second
      occasion full MPA AUC0-12 calculated using the linear trapezoidal rule. Bias
      (median percentage prediction error) and imprecision (median absolute prediction
      error) were determined. RESULTS: Median percentage prediction error and median
      absolute prediction error for the prediction of full MPA AUC0-12 were <15% for 4
      LSSs, using the data from the same (second) occasion. One equation (1.583C1 +
      0.765C2 + 0.369C2.5 + 0.748C3 + 1.518C4 + 2.158C6 + 3.292C8 + 3.6690) showed bias
      and imprecision <15% for the prediction of future MPA AUC0-12, where the
      predicted AUC0-12 from the first occasion was compared with the full AUC0-12 from
      the second. All LSSs with an acceptable predictive performance included
      concentrations taken at least 6 hours after the dose. CONCLUSIONS: Only one LSS
      had an acceptable bias and precision for future estimation. Accurate dosage
      prediction using a multiple linear regression-based LSS was not possible without
      concentrations up to at least 8 hours after the dose.

PMID- 29461445
TI  - Impact of Anesthesia on Hospital Mortality and Morbidities in Geriatric Patients
      Following Emergency Hip Fracture Surgery.
AB  - OBJECTIVES: To determine the impact of anesthesia type on in-hospital mortality
      and morbidity for geriatric fragility hip fracture surgery. DESIGN: Retrospective
      cohort study. SETTING: Integrates health care delivery system across 38
      facilities in the United States. PATIENTS/PARTICIPANTS: We identified 16,695
      patients 65 years of age and older who underwent emergent hip fracture repairs
      between 2009 and 2014 through the Kaiser Permanente hip fracture registry and
      excluded pathologic or bilateral fractures. INTERVENTION: Hip fracture surgery
      with general or regional anesthesia. MAIN OUTCOMES MEASURES: Data on in-hospital
      mortality, time to death, discharge disposition, and length of stay (LOS) were
      analyzed among the following anesthesia types: general anesthesia (GA), regional
      anesthesia (RA), and intraoperative conversions from regional to general (Cv).
      RESULTS: Compared with RA, the hazard ratio for GA for in-hospital mortality was
      1.38 and 2.23 for the Cv group; the time ratio for GA-associated time to death
      was 0.97 and 0.89 for the Cv group. The GA-associated time ratio for LOS before
      discharge was 1.01, and the hazard ratio for home discharge was 0.86, but no
      significance was found with the Cv group. CONCLUSIONS: RA may offer advantages
      over GA for fragility hip fracture surgeries when possible. In-hospital
      mortality, time to death, increased LOS, and discharge to an institute rather
      than home were all adversely influenced by GA. Furthermore, the previously
      understudied Cv group demonstrated adverse outcomes for in-hospital mortality and
      time to death. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 29461446
TI  - Evaluating the Utility of the Lateral Elbow Radiograph in Central Articular
      Olecranon Reduction: An Anatomic and Radiographic Study.
AB  - OBJECTIVES: The surgical reduction of intra-articular olecranon fractures is
      judged primarily on the lateral elbow radiograph, as orthogonal imaging of the
      articular surface is not obtainable. We sought to determine surgeon accuracy in
      identifying intra-articular olecranon malreductions on the lateral elbow
      radiograph. METHODS: Six human fresh-frozen cadaveric elbow specimens were
      sagittally sectioned in 5-mm increments after olecranon dissection, preservation
      of soft tissue envelope, and rigid fixation of the elbow in an external fixator.
      Three patterns of central intra-articular olecranon malreduction were created in
      each elbow using a ruler and bone saw. Perfect lateral elbow radiographs were
      taken of each malreduction, and these images were randomized along with x-rays of
      normal cadaveric olecranons. The image series was presented to 4 masked trauma
      trained surgeons to determine whether the olecranon was malreduced or anatomic.
      Surgeons interpreted the same image series on 2 separate occasions separated by 6
      weeks. Percent correct was recorded, and the interobserver and intraobserver
      reliability was calculated. RESULTS: Orthopedic trauma surgeons correctly
      identified olecranon malreductions only 73% of the time on the lateral elbow
      radiograph. Interobserver agreement was moderate for the first review of images
      and fair for the second review, with respective Fleiss Kappa values of 0.43 and
      0.28. Intrarater reliability revealed moderate agreement with Cohen's Kappa value
      ranging from 0.56 to 0.66. CONCLUSIONS: Intra-articular olecranon malreductions
      are inconsistently recognized by trauma surgeons on the lateral elbow radiograph.
      Therefore, articular incongruity may still be present after surgical fixation of
      comminuted olecranon fractures. We must further define the radiographic anatomic
      representation of the articular olecranon to improve surgical reduction and
      clinical outcomes.

PMID- 29461447
TI  - Infliximab Plus Intravenous Immunoglobulin (IVIG) Versus IVIG Alone as Initial
      Therapy in Children With Kawasaki Disease Presenting With Coronary Artery
      Lesions: Is Dual Therapy More Effective?
AB  - BACKGROUND: We previously demonstrated that 80% of Kawasaki disease (KD) patients
      who develop coronary artery lesions (CALs) have them at diagnosis. We postulated
      that KD patients presenting with CALs represent a group that may benefit from
      more aggressive initial therapy. Infliximab has been shown to decrease
      inflammation in KD patients when added to standard therapy. We compared outcomes
      of KD patients with CALs initially treated with intravenous immunoglobulin (IVIG)
      alone versus IVIG plus infliximab. METHODS: Medical records of KD patients from
      January 2009 to July 2016 were retrospectively reviewed. CALs were defined as a
      left anterior descending or right coronary artery Z score >=2.5. KD patients with
      CALs on initial echocardiogram treated with IVIG alone were compared with those
      treated with IVIG plus infliximab. Clinical characteristics were compared between
      groups using Wilcoxon rank-sum test, chi test and Fischer's exact tests; length
      of stay was analyzed using log-normal regression and need for additional therapy
      using logistic regression. Effect of treatment on CALs between groups was
      assessed using linear mixed models. RESULTS: Sixty-nine KD patients with CALs at
      presentation were included. Fifteen of 34 (44%) patients treated with IVIG alone
      required additional therapy compared with 4 of 35 (11%) patients treated with
      IVIG plus infliximab (P = 0.003). There were no significant differences between
      treatment groups for length of stay, CALs or C-reactive protein fall.
      CONCLUSIONS: IVIG plus infliximab as initial therapy reduces the need for
      additional therapy in KD patients presenting with CALs. Intensified initial
      therapy, consisting of infliximab plus IVIG, could be considered for this group
      of KD patients.

PMID- 29461448
TI  - Aerococcus urinae as the Causative Agent in Infective Endocarditis of the Aortic
      Valve in a Pediatric Patient.
AB  - Aerococcus species were first described in 1953. They have been previously
      described as the causative agent of urinary tract infections in the elderly but
      rarely the causative agent for severe infections. However, there are very few
      cases reported in the pediatric population. To our knowledge, we report the first
      case of an adolescent with infective endocarditis caused by Aerococcus urinae.

PMID- 29461449
TI  - Optimizing Vancomycin Monitoring in Pediatric Patients.
AB  - BACKGROUND: Several studies have reported that trough levels may not be optimal
      for monitoring vancomycin therapy, because of overexposure and nephrotoxicity
      risks. Therefore, we developed a population pharmacokinetic model to optimize
      vancomycin dosing and monitoring in pediatrics. METHODS: Data were
      retrospectively collected on 76 pediatric patients 1-12 years of age, admitted to
      general pediatric wards or intensive care units at King Saud University Medical
      City, Riyadh, Saudi Arabia. The predictability of 3 methods for calculating the
      area under the curve (AUC) at steady state was assessed for optimum vancomycin
      therapy monitoring. The 3 methods were simple linear regression, Bayesian
      approach and the 2-sample pharmacokinetic equation method. We also used Monet
      Carlo simulations to evaluate the dosing of vancomycin. RESULTS: A 1-compartment
      model adequately described the data. A strong correlation occurred between the
      observed and predicted AUC from 0 to 24 hours (AUC0-24h) calculated using the
      Bayesian approach with a trough sample only or pharmacokinetic equations based on
      2 measured samples (R = 0.93 and 0.92, respectively). For the simple linear
      regression method with a trough sample only, the predicted AUC0-24h at steady
      state with vancomycin trough levels of 10, 15 and 20 ug/mL were 413, 548 and 714
      ug.hour/mL, respectively. The target AUC0-24h above 400 was achieved in 46% and
      95% of individuals with trough values of 7-11 and 11-15 ug/mL, respectively.
      Monte Carlo simulations showed that 60-80 mg/kg/d doses are needed to optimize
      vancomycin therapy. CONCLUSIONS: In conclusion, targeting vancomycin trough
      levels above 15 ug/mL in pediatrics would overshoot the target AUC0-24h above 400
      and expose them to unnecessary adverse events.

PMID- 29461450
TI  - Utility of the Performance of Lumbar Puncture for Febrile Children With Status
      Epilepticus in the Bacterial Conjugate Vaccine Era.
AB  - BACKGROUND: The necessity of lumbar puncture for the differentiation of central
      nervous system infection in children with febrile status epilepticus (FSE)
      remains controversial. The aim of the present study is to investigate the
      diagnostic necessity of lumbar puncture for children with FSE after the
      introduction of bacterial conjugate vaccines into the infant immunization
      program. METHODS: Our retrospective cohort study was performed in children 6 to
      60 months of age who were admitted to the pediatric ward at Kitakyushu General
      Hospital from January 1, 2011, to December 31, 2015, for seizures with fever. Of
      these patients, we compared the clinical characteristics between the patients
      initially diagnosed as having FSE and complex febrile seizures excluding FSE (non
      FSE). RESULTS: Of the eligible 333 children, 98 and 235 children were classified
      into FSE and non-FSE groups, respectively. The proportion of the children who
      underwent lumbar puncture in FSE group was significantly higher than that in non
      FSE group (P < 0.0001). On the other hand, no significant difference in the
      proportion of the patients with abnormal cerebrospinal fluid findings was seen
      between the 2 groups. There was no patient with bacterial meningitis. The
      proportion of patients with encephalitis/encephalopathy in FSE group (n = 7,
      7.1%) was significantly higher than that in non-FSE group (n = 0, P = 0.0003).
      However, only 1 of 6 patients with encephalitis/encephalopathy who underwent
      lumber puncture showed pleocytosis in cerebrospinal fluid. CONCLUSIONS: Routine
      lumbar puncture for the differentiation of severe central nervous system
      infection cannot be recommended in children with FSE.

PMID- 29461451
TI  - Similarities and Differences Between Physician Assistant Program and Medical
      School Mission Statement Themes.
AB  - PURPOSE: The purpose of this study was to examine the concordance of US physician
      assistant (PA) program mission statements with those of US public- and private
      sponsored medical schools. With the exception of a broader medical school focus
      on research, the authors hypothesized that little difference in mission statement
      congruence would be found in a comparison of medical schools and PA programs.
      METHODS: Mission statements of 209 of the 210 accredited US PA programs as of May
      2016 were obtained and analyzed. Keywords and phrases were identified, coded, and
      analyzed using NVivo. Themes that previously reported medical school mission
      statement analyses (including education, research, service, primary care,
      diversity, prevention, provider distribution, and cost control) were examined.
      Additional themes of evidence-based medicine (EBM), interprofessional care,
      patient safety, and quality improvement were included in the analyses. RESULTS:
      Analyses revealed similar emphasis in both PA programs and medical schools on
      themes of education, prevention, and cost control, with dissimilar emphases on
      themes of research, service, primary care, diversity, and provider distribution.
      Physician assistant programs were more likely to emphasize interprofessional care
      than EBM, patient safety, or quality improvement. CONCLUSIONS: In the comparison
      of mission statements of medical schools and PA programs, much less congruence
      was found than had been hypothesized. Although this study examined the
      similarities and differences between the mission statements of US medical schools
      and PA programs, it did not examine the extent to which programs succeeded in
      meeting the stated missions. Additional research is necessary to understand the
      factors that determine whether mission statements are actualized in measurable
      deliverables.

PMID- 29461452
TI  - Continuing Dermatology Education for Rural Physician Assistants in Ghana: An
      Assessment of Needs and Effectiveness.
AB  - PURPOSE: To assess the effectiveness of lectures for continuing medical education
      (CME) in dermatology in a global health setting and to determine provider and
      patient demographics of physician assistants (PAs) practicing in rural Ghana.
      METHODS: Physician assistants from Ghana who attended dermatology lectures at the
      International Seminar for Physician Assistants in 2011 or 2014 were included in
      this study. Surveys were administered to participants to determine dermatology
      resource availability, commonly encountered skin diseases, and management
      practices. Quizzes were administered before and after CME dermatology lectures to
      assess short-term retention of lecture material. RESULTS: In all, 353 PAs
      participated in this study. Physician assistants reported seeing an average of 55
      patients per day. The most commonly seen skin diseases were infections, with
      antifungals and antibiotics being the most commonly prescribed medications.
      Dermatology-related complaints represented 9.5% of total clinic visits. Among
      practicing PAs, 23.2% reported having internet access. A total of 332 PAs
      completed the quizzes, and a statistically significant increase in test scores
      was noted in postlecture quizzes. CONCLUSIONS: This study reinforces the
      importance of dermatology education for PAs practicing in rural areas of Ghana
      and lends insight to critical topics for dermatology curriculum development. In
      addition, the increase in test scores after CME sessions suggests that lectures
      are an effective tool for short-term retention of dermatology-related topics. Our
      study indicates that as the need for health workers increases globally and a
      paradigm shift away from the traditional physician model of care occurs,
      dermatology training of PAs is not only important but also achievable.

PMID- 29461453
TI  - Noncognitive Attributes in Physician Assistant Education.
AB  - Physician assistant (PA) admissions processes have typically given more weight to
      cognitive attributes than to noncognitive ones, both because a high level of
      cognitive ability is needed for a career in medicine and because cognitive
      factors are easier to measure. However, there is a growing consensus across the
      health professions that noncognitive attributes such as emotional intelligence,
      empathy, and professionalism are important for success in clinical practice and
      optimal care of patients. There is also some evidence that a move toward more
      holistic admissions practices, including evaluation of noncognitive attributes,
      can have a positive effect on diversity. The need for these noncognitive
      attributes in clinicians is being reinforced by changes in the US health care
      system, including shifting patient demographics and a growing emphasis on team
      based care and patient satisfaction, and the need for clinicians to help patients
      interpret complex medical information. The 2016 Physician Assistant Education
      Association Stakeholder Summit revealed certain behavioral and affective
      qualities that employers of PAs value and sometimes find lacking in new
      graduates. Although there are still gaps in the evidence base, some tools and
      technologies currently exist to more accurately measure noncognitive variables.
      We propose some possible strategies and tools that PA programs can use to
      formalize the way they select for noncognitive attributes. Since PA programs
      have, on average, only 27 months to educate students, programs may need to focus
      more resources on selecting for these attributes than teaching them.

PMID- 29461454
TI  - A Program's Analysis of Communication Methods With Clinical Preceptors.
AB  - PURPOSE: Preceptors value communication with physician assistant (PA) educational
      programs. This study describes preceptors' perspectives about one PA program's
      established and new communication strategies to promote preceptor development and
      retention. METHODS: An electronic survey of preceptors was conducted in December
      2014. Quantitative and qualitative data were analyzed using descriptive
      statistics. RESULTS: Eighty-eight of 209 preceptors completed the survey (42%
      response rate). Preceptors reported satisfaction with communication frequency and
      quality. The most preferred topics were preceptor benefits, teaching strategies,
      feedback about students' performance, and program policy updates. Many preceptors
      reported not receiving communications sent by mail. A majority of preceptors
      preferred site visits at least once per year and in person. CONCLUSIONS:
      Understanding preceptors' preferred topics helped the study program increase its
      emphasis on those topics. Knowledge that many preceptors do not receive mailed
      communications has prompted the program to use electronic communication for all
      communication types. The results reinforced the program's approach to site
      visits.

PMID- 29461455
TI  - Students at Risk: Addressing Mental Health Issues and Their Legal Implications in
      Health Professions Students.

PMID- 29461457
TI  - Short-Term Medical Missions Done Well: What Every Sponsoring Institution Should
      Understand.

PMID- 29461456
TI  - Teaching Physician Assistant Students Real-World Evidence-Based Medicine.

PMID- 29461458
TI  - Leveraging E-Learning for Pedagogical Innovation in PA Education.

PMID- 29461460
TI  - Shortening the Half-Life of IgG as a Strategy for Decreasing Alloantibodies.

PMID- 29461461
TI  - Velma Scantlebury, MD: First African American Female Transplant Surgeon.

PMID- 29461462
TI  - FES-assisted Cycling Improves Aerobic Capacity and Locomotor Function
      Postcerebrovascular Accident.
AB  - PURPOSE: After a cerebrovascular accident (CVA) aerobic deconditioning
      contributes to diminished physical function. Functional electrical stimulation
      (FES)-assisted cycling is a promising exercise paradigm designed to target both
      aerobic capacity and locomotor function. This pilot study aimed to evaluate the
      effects of an FES-assisted cycling intervention on aerobic capacity and locomotor
      function in individuals post-CVA. METHODS: Eleven individuals with chronic (>6
      months) post-CVA hemiparesis completed an 8-wk (three times per week; 24
      sessions) progressive FES-assisted cycling intervention. VO2peak, self-selected,
      and fastest comfortable walking speeds, gait, and pedaling symmetry, 6-min walk
      test (6MWT), balance, dynamic gait movements, and health status were measured at
      baseline and posttraining. RESULTS: Functional electrical stimulation-assisted
      cycling significantly improved VO2peak (12%, P = 0.006), self-selected walking
      speed (SSWS, 0.05 +/- 0.1 m.s, P = 0.04), Activities-specific Balance Confidence
      scale score (12.75 +/- 17.4, P = 0.04), Berg Balance Scale score (3.91 +/- 4.2, P
      = 0.016), Dynamic Gait Index score (1.64 +/- 1.4, P = 0.016), and Stroke Impact
      Scale participation/role domain score (12.74 +/- 16.7, P = 0.027). Additionally,
      pedal symmetry, represented by the paretic limb contribution to pedaling (paretic
      pedaling ratio [PPR]) significantly improved (10.09% +/- 9.0%, P = 0.016).
      Although step length symmetry (paretic step ratio [PSR]) did improve, these
      changes were not statistically significant (-0.05% +/- 0.1%, P = 0.09).
      Exploratory correlations showed moderate association between change in SSWS and 6
      min walk test (r = 0.74), and moderate/strong negative association between change
      in PPR and PSR. CONCLUSIONS: These results support FES-assisted cycling as a
      means to improve both aerobic capacity and locomotor function. Improvements in
      SSWS, balance, dynamic walking movements, and participation in familial and
      societal roles are important targets for rehabilitation of individuals after CVA.
      Interestingly, the correlation between PSR and PPR suggests that improvements in
      pedaling symmetry may translate to a more symmetric gait pattern.

PMID- 29461463
TI  - Prognostic Value of The Lactate/Albumin Ratio for Predicting 28-Day Mortality in
      Critically ILL Sepsis Patients.
AB  - AIM: The aim of this study was to evaluate the clinical utility of the
      lactate/albumin (L/A) ratio as a predictive factor of 28-day mortality in
      critically ill sepsis patients. METHODS: This is a retrospective observational
      study from a prospectively collected multicenter registry of 10 emergency
      departments (EDs) in teaching hospitals that participated in the Korean Shock
      Society. It enrolled patients who were 19 years of age or older who had a
      suspected or confirmed infection and evidence of refractory hypotension or
      hypoperfusion. The prognostic performance of the L/A ratio and lactate level for
      predicting 28-day mortality was assessed. Lactate and albumin levels were
      measured immediately after ED arrival. RESULTS: A total of 946 patients were
      included, with 22.5% overall 28-day mortality. The area under the receiver
      operating characteristic curve (AUROC) value of the L/A ratio (0.69, 95%
      confidence interval [CI] 0.64-0.73, P < 0.01) was higher than that of lactate
      (0.65, 95% CI 0.61-0.70, P < 0.01) for predicting 28-day mortality. The optimal
      cutoff of the L/A ratio was 1.32. The AUROC value of the L/A ratio was better
      than that of lactate regardless of lactate level (normal [<2.0 mmol/L]: 0.68 vs.
      0.55; intermediate [>=2.0, < 4.0 mmol/L]: 0.65 vs. 0.50; high [>=4.0 mmol/L]:
      0.66 vs. 0.62). In the subgroup with decreased lactate elimination, the AUROC
      value of the L/A ratio was also significantly higher than that of lactate
      (hepatic dysfunction: 0.70 vs. 0.66; renal dysfunction: 0.71 vs. 0.67). The L/A
      ratio cut-off and hypoalbminemia showed further discriminative value for 28-day
      mortality even in patients with normal or intermediate lactate levels.
      CONCLUSIONS: The prognostic performance of the L/A ratio was superior to that of
      a single lactate measurement for predicting 28-day mortality of critically ill
      sepsis patients. L/A ratio can be a useful prognostic factor regardless of
      initial lactate level and the presence of hepatic or renal dysfunction.

PMID- 29461464
TI  - Protective Effects of the Complement Inhibitor Compstatin CP40 in Hemorrhagic
      Shock.
AB  - Trauma-induced hemorrhagic shock (HS) plays a decisive role in the development of
      immune, coagulation, and organ dysfunction often resulting in a poor clinical
      outcome. Imbalanced complement activation is intricately associated with the
      molecular danger response and organ damage after HS. Thus, inhibition of the
      central complement component C3 as turnstile of both inflammation and coagulation
      is hypothesized as a rational strategy to improve the clinical course after
      HS.Applying intensive care conditions, anaesthetized, monitored, and protectively
      ventilated non-human primates (NHP; cynomolgus monkeys) received a pressure
      controlled severe HS (60 min at MAP 30 mmHg) with subsequent volume
      resuscitation. Thirty min after HS, animals were randomly treated with either an
      analog of the C3 inhibitor compstatin (i.e., Cp40) in saline (n = 4) or with
      saline alone (n = 4). The observation period lasted 300 min after induction of
      HS.We observed improved kidney function in compstatin Cp40-treated animals after
      HS as determined by improved urine output, reduced damage markers and a tendency
      of less histopathological signs of acute kidney injury. Sham-treated animals
      revealed classical signs of mucosal edema, especially in the ileum and colon
      reflected by worsened microscopic intestinal injury scores. In contrast, Cp40
      treated HS animals exhibited only minor signs of organ edema and significantly
      less intestinal damage. Furthermore, early systemic inflammation and coagulation
      dysfunction were both ameliorated by Cp40.The data suggest that therapeutic
      inhibition of C3 is capable to significantly improve immune, coagulation and
      organ function and to preserve organ-barrier integrity early after traumatic HS.
      C3-targeted complement inhibition may therefore reflect a promising therapeutic
      strategy in fighting fatal consequences of HS.

PMID- 29461465
TI  - Septic Shock Alters Mitochondrial Respiration of Lymphoid Cell-Lines and Human
      Peripheral Blood Mononuclear Cells: The Role of Plasma.
AB  - INTRODUCTION: In septic shock patients, post-septic immunosuppression state
      following the systemic inflammatory response syndrome is responsible for
      nosocomial infections, with subsequent increased mortality. The aim of the
      present study was to assess the underlying cellular mechanisms of the post-septic
      immunosuppression state, by investigating mitochondrial functions of peripheral
      blood mononuclear cells (PBMCs) from septic shock patients over 7 days. MATERIALS
      AND METHODS: Eighteen patients admitted to a French intensive care unit for
      septic shock were included. At days 1 and 7, PBMCs were isolated by Ficoll
      density gradient centrifugation. Mitochondrial respiration of intact septic PBMCs
      was assessed versus control group PBMCs, by measuring O2 consumption in plasma,
      using high-resolution respirometry. Mitochondrial respiration was then compared
      between septic plasmas and control plasmas for control PBMCs, septic PBMCs and
      lymphoid cell-line (CEM). To investigate the role of plasma, we measured several
      plasma cytokines, among them HMGB1, by ELISA. RESULTS: Basal O2 consumption of
      septic shock PBMCs was of 8.27 +/- 3.39 and 10.48 +/- 3.99 pmol/s/10 cells at
      days 1 and 7 respectively, significantly higher than in control PBMCs (5.37 +/-
      1.46 pmol/s/10 cells, p < 0.05). Septic patient PBMCs showed a lower response to
      oligomycin, suggesting a reduced ATP-synthase activity, as well as an increased
      response to FCCP suggesting an increased mitochondrial respiratory capacity. At 6
      hours, septic plasmas showed a decreased O2 consumption of CEM (4.73 +/- 1.46 vs.
      6.58 +/- 1.53, p < 0.05) as well as in control group PBMCs (1.76 +/- 0.36 vs.
      2.70 +/- 0.42, p < 0.05), and triggered a decreased ATP-synthase activity but an
      increased response to FCCP. These differences are not explained by different cell
      survival. High HMGB1 levels were significantly associated with reduced PBMCs
      mitochondrial respiration. CONCLUSION: Septic plasma impairs mitochondrial
      respiration in immune cells, with a possible role of the proinflammatory protein
      HMGB1, leading to a subsequent compensation, probably by enzymatic activation.
      This compensation result is an improvement of global mitochondrial respiratory
      capacity, but without restoring ATP-synthase activity.

PMID- 29461466
TI  - Characterization of the Key Aroma Compounds in Proso Millet Wine Using Headspace
      Solid-Phase Microextraction and Gas Chromatography-Mass Spectrometry.
AB  - The volatile compounds in proso millet wine were extracted by headspace solid
      phase microextraction (85 MUm polyacrylate (PA), 100 MUm polydimethylsiloxane
      (PDMS), 75 MUm Carboxen (CAR)/PDMS, and 50/30 MUm divinylbenzene (DVB)/CAR/PDMS
      fibers), and analyzed using gas chromatography-mass spectrometry; the odor
      characteristics and intensities were analyzed by the odor activity value (OAV).
      Different sample preparation factors were used to optimize this method: sample
      amount, extraction time, extraction temperature, and content of NaCl. A total of
      64 volatile compounds were identified from the wine sample, including 14 esters,
      seven alcohols, five aldehydes, five ketones, 12 benzene derivatives, 12
      hydrocarbons, two terpenes, three phenols, two acids, and two heterocycles. Ethyl
      benzeneacetate, phenylethyl alcohol, and benzaldehyde were the main volatile
      compounds found in the samples. According to their OAVs, 14 volatile compounds
      were determined to be odor-active compounds (OAV > 1), and benzaldehyde,
      benzeneacetaldehyde, 1-methyl-naphthalene, 2-methyl-naphthalene, and biphenyl
      were the prominent odor-active compounds (OAV > 50), having a high OAV. Principal
      component analysis (PCA) showed the difference of distribution of the 64 volatile
      compounds and 14 odor-active compounds with four solid-phase microextraction
      (SPME) fibers.

PMID- 29461467
TI  - Genome-Wide Analysis of the GRF Family Reveals Their Involvement in Abiotic
      Stress Response in Cassava.
AB  - GENERAL REGULATORY FACTOR (GRF) proteins play vital roles in the regulation of
      plant growth, development, and response to abiotic stress. However, little
      information is known for this gene family in cassava (Manihot esculenta). In this
      study, 15 MeGRFs were identified from the cassava genome and were clustered into
      the epsilon and the non-epsilon groups according to phylogenetic, conserved
      motif, and gene structure analyses. Transcriptomic analyses showed eleven MeGRFs
      with constitutively high expression in stems, leaves, and storage roots of two
      cassava genotypes. Expression analyses revealed that the majority of GRFs showed
      transcriptional changes under cold, osmotic, salt, abscisic acid (ABA), and H2O2
      treatments. Six MeGRFs were found to be commonly upregulated by abiotic stress,
      ABA, and H2O2 treatments, which may be the converging points of multiple
      signaling pathways. Interaction network analysis identified 18 possible
      interactors of MeGRFs. Taken together, this study elucidates the transcriptional
      control of MeGRFs in tissue development and the responses of abiotic stress and
      related signaling in cassava. Some constitutively expressed, tissue-specific, and
      abiotic stress-responsive candidate MeGRF genes were identified for the further
      genetic improvement of crops.

PMID- 29461469
TI  - The Prediction of the Gas Utilization Ratio based on TS Fuzzy Neural Network and
      Particle Swarm Optimization.
AB  - Gas utilization ratio (GUR) is an important indicator that is used to evaluate
      the energy consumption of blast furnaces (BFs). Currently, the existing methods
      cannot predict the GUR accurately. In this paper, we present a novel data-driven
      model for predicting the GUR. The proposed approach utilized both the TS fuzzy
      neural network (TS-FNN) and the particle swarm algorithm (PSO) to predict the
      GUR. The particle swarm algorithm (PSO) is applied to optimize the parameters of
      the TS-FNN in order to decrease the error caused by the inaccurate initial
      parameter. This paper also applied the box graph (Box-plot) method to eliminate
      the abnormal value of the raw data during the data preprocessing. This method can
      deal with the data which does not obey the normal distribution which is caused by
      the complex industrial environments. The prediction results demonstrate that the
      optimization model based on PSO and the TS-FNN approach achieves higher
      prediction accuracy compared with the TS-FNN model and SVM model and the proposed
      approach can accurately predict the GUR of the blast furnace, providing an
      effective way for the on-line blast furnace distribution control.

PMID- 29461468
TI  - Bullying as a Stressor in Mid-Adolescent Girls and Boys-Associations with
      Perceived Stress, Recurrent Pain, and Salivary Cortisol.
AB  - Bullying involves repeated exposure to negative actions while also invoking a
      power asymmetry between the involved parties. From a stress perspective, being
      bullied can be seen as a severe and chronic stressor, and an everyday social
      evaluative threat, coupled with a shortage of effective social resources for
      dealing with this particular stressor. The aim of this study was to investigate
      whether exposure to bullying among mid-adolescent girls and boys is associated
      with subjective and objective stress-related outcomes in terms of perceived
      stress, recurrent pain, and salivary cortisol. The data came from the School
      Stress and Support Study (TriSSS) including students in grades 8-9 in two schools
      in Stockholm, Sweden, in 2010 (study sample n = 392; cortisol subsample n = 198).
      Bullying was self-reported and measured by multiple items. The statistical
      analyses included binary logistic and linear (OLS) regression. Being bullied was
      associated with greater perceived stress and an increased risk of recurrent pain,
      among both boys and girls. Also, bullied students had lower cortisol output
      (AUCG) and lower cortisol awakening response (CARG) as compared to those who were
      not bullied. Gender-stratified analyses demonstrated that these associations were
      statistically significant for boys but not for girls. In conclusion, this study
      demonstrated that being bullied was related to both subjective and objective
      stress markers among mid-adolescent girls and boys, pointing to the necessity of
      continuously working against bullying.

PMID- 29461470
TI  - Three-Level De-Multiplexed Dual-Branch Complex Delta-Sigma Transmitter.
AB  - In this paper, a dual-branch topology driven by a Delta-Sigma Modulator (DSM)
      with a complex quantizer, also known as the Complex Delta Sigma Modulator
      (CxDSM), with a 3-level quantized output signal is proposed. By de-multiplexing
      the 3-level Delta-Sigma-quantized signal into two bi-level streams, an efficiency
      enhancement over the operational frequency range is achieved. The de-multiplexed
      signals drive a dual-branch amplification block composed of two switch-mode back
      to-back power amplifiers working at peak power. A signal processing technique
      known as quantization noise reduction with In-band Filtering (QNRIF) is applied
      to each of the de-multiplexed streams to boost the overall performances;
      particularly the Adjacent Channel Leakage Ratio (ACLR). After amplification, the
      two branches are combined using a non-isolated combiner, preserving the
      efficiency of the transmitter. A comprehensive study on the operation of this
      topology and signal characteristics used to drive the dual-branch Switch-Mode
      Power Amplifiers (SMPAs) was established. Moreover, this work proposes a highly
      efficient design of the amplification block based on a back-to-back power
      topology performing a dynamic load modulation exploiting the non-overlapping
      properties of the de-multiplexed Complex DSM signal. For experimental validation,
      the proposed de-multiplexed 3-level Delta-Sigma topology was implemented on the
      BEEcubeTM platform followed by the back-to-back Class-E switch-mode power
      amplification block. The full transceiver is assessed using a 4th-Generation
      mobile communications standard LTE (Long Term Evolution) standard 1.4 MHz signal
      with a peak to average power ratio (PAPR) of 8 dB. The dual-branch topology
      exhibited a good linearity and a coding efficiency of the transmitter chain
      higher than 72% across the band of frequency from 1.8 GHz to 2.7 GHz.

PMID- 29461471
TI  - Heavy Metals in Notifications of Rapid Alert System for Food and Feed.
AB  - Heavy metals represent the fourth most often notified hazard category in the
      Rapid Alert System for Food and Feed (RASFF) from 1980-2016. The goal of the
      study was to examine the similarities in notifications of particular heavy metals
      within the RASFF year, product category, notifying country, country of origin,
      notification basis, notification type, distribution status, risk decision, and
      action taken, taking into account the particular product type, such as food, food
      contact material, and feed. The data originated from the RASFF database. Cluster
      analysis on pivot tables was applied using joining and two-way joining methods.
      Most notifications concerned food, in which the highest number were related to
      mercury, cadmium, chromium, lead, arsenic, and nickel. Notifications were mainly
      related to fish and food contact materials, in addition to fruits and vegetables,
      seafood, and dietetic food. The number of notifications decreased in 2015 and
      2016. The majority of products were notified by Italy, Spain, Germany, and
      France. The notified products originated mainly from China and Spain. The
      notification was usually based on official controls on the market, as well as
      border controls. The notification types were mainly information, alert, and
      border rejections. Products were not frequently distributed due to distribution
      restriction to the notifying country or the possibility of distribution to the
      market. A risk decision was not usually made. The taken actions included re
      dispatch of products, withdrawal from the market, or destruction. The data on
      heavy metals from the RASFF database can help European and national authorities
      in shaping public health.

PMID- 29461472
TI  - In the Eye of the Beholder: Owner Preferences for Variations in Cats' Appearances
      with Specific Focus on Skull Morphology.
AB  - Changes in the popularity of cat breeds are largely driven by human perceptions
      of, and selection for, phenotypic traits including skull morphology. The
      popularity of breeds with altered skull shapes appears to be increasing, and
      owner preferences are an important part of this dynamic. This study sought to
      establish how and why a range of phenotypic attributes, including skull shape,
      affect preferences shown by cat owners. Two questionnaires were distributed on
      line to cat owners who were asked to rate preferences for pictures of cats on a 0
      10 scale. Veterinarian consensus established the skull types of the cats pictured
      (i.e., level of brachycephaly (BC) or dolichocephaly (DC)). Preferences were then
      explored relative to cat skull type, coat and eye color, and coat length.
      Generalized estimating equations identified relationships between physical
      characteristics and respondent ratings. Further sub-analyses explored effects of
      respondents' occupation, location and previous cat ownership on rating scores.
      Overall, cats with extreme changes in skull morphology (both BC and DC) were
      significantly less preferred than mesocephalic cats. Green eyes, ginger coat
      color and medium length coat were most preferred. Current owners of a BC or DC
      pure bred cat showed significantly greater preference for cats with similar
      features and significantly lower preference for the opposite extreme. Respondents
      from Asia were significantly more likely to prefer both BC and DC cats as
      compared to respondents from other locations. Finally, those in an animal care
      profession, as compared to other professions, provided a significantly lower
      preference rating for BC cats but not for DC cats. This work, despite the
      acknowledged limitations, provides preliminary evidence that preferences for cat
      breeds, and their associated skull morphologies, are driven by both cultural and
      experiential parameters. This information may allow for better targeting of
      educational materials concerning cat breeds.

PMID- 29461473
TI  - Temporal and Fine-Grained Pedestrian Action Recognition on Driving Recorder
      Database.
AB  - The paper presents an emerging issue of fine-grained pedestrian action
      recognition that induces an advanced pre-crush safety to estimate a pedestrian
      intention in advance. The fine-grained pedestrian actions include visually slight
      differences (e.g., walking straight and crossing), which are difficult to
      distinguish from each other. It is believed that the fine-grained action
      recognition induces a pedestrian intention estimation for a helpful advanced
      driver-assistance systems (ADAS). The following difficulties have been studied to
      achieve a fine-grained and accurate pedestrian action recognition: (i) In order
      to analyze the fine-grained motion of a pedestrian appearance in the vehicle
      mounted drive recorder, a method to describe subtle change of motion
      characteristics occurring in a short time is necessary; (ii) even when the
      background moves greatly due to the driving of the vehicle, it is necessary to
      detect changes in subtle motion of the pedestrian; (iii) the collection of large
      scale fine-grained actions is very difficult, and therefore a relatively small
      database should be focused. We find out how to learn an effective recognition
      model with only a small-scale database. Here, we have thoroughly evaluated
      several types of configurations to explore an effective approach in fine-grained
      pedestrian action recognition without a large-scale database. Moreover, two
      different datasets have been collected in order to raise the issue. Finally, our
      proposal attained 91.01% on National Traffic Science and Environment Laboratory
      database (NTSEL) and 53.23% on the near-miss driving recorder database (NDRDB).
      The paper has improved +8.28% and +6.53% from baseline two-stream fusion
      convnets.

PMID- 29461474
TI  - Parental Education and Pre-School Children's Objectively Measured Sedentary Time:
      The Role of Co-Participation in Physical Activity.
AB  - Parental co-participation in physical activity (PA) may be a beneficial parenting
      practice for diminishing children's sedentary time (ST). Less information is
      available, however, on the explanatory role of co-participation in PA regarding
      parental educational differences in children's ST. Preschool-aged children (N =
      864, mean age 4.8, 52% boys) with their parents participated in a cross-sectional
      DAGIS (Increased Health and Wellbeing in Pre-schools) study between years 2015
      and 2016. Children (N = 821) wore an accelerometer for one week. Parents were
      informed of their educational background, and the frequency of visits with their
      child in nature, to parks or playgrounds, their own yard, and indoor sport
      facilities (N = 808). Testing the associations required multiple regression
      analyses. Parents with a low educational background reported more frequent visits
      with their child to their own yard, and these visits were associated with
      children's lower ST. More highly educated parents co-visited indoor sport
      facilities more frequently, although this did not have a significant association
      with children's ST. More frequent visits in nature were associated with a lower
      ST at weekends, regardless of educational background. Future health promotion
      strategies should inform parents that frequent co-participation in PA, for
      example, in one's own yard, is beneficial for lowering children's ST.

PMID- 29461475
TI  - Octodrine: New Questions and Challenges in Sport Supplements.
AB  - Background: Octodrine is the trade name for Dimethylhexylamine (DMHA), a central
      nervous stimulant that increases the uptake of dopamine and noradrenaline.
      Originally developed as a nasal decongestant in the 1950's, it has recently been
      re-introduced on the market as a pre-workout and 'fat-burner' product but its use
      remains unregulated. Our work provides the first observational cross-sectional
      analytic study on Octodrine as a new drug trend and its associated harms after a
      gap spanning seven decades. Methods: A comprehensive multilingual assessment of
      literature, websites, drug fora and other online resources was carried out with
      no time restriction in English, German, Russian and Arabic. Keywords included
      Octodrine's synonyms and chemical isomers. Results: Only five relevant
      publications emerged from the literature search, with most of the available data
      on body building websites and fora. Since 2015, Octodrine has been advertised
      online as "the next big thing" and "the god of stimulants," with captivating
      marketing strategies directed at athletes and a wider cohort of users. Reported
      side-effects include hypertension, dyspnoea and hyperthermia. Conclusions: The
      uncontrolled use of Octodrine, its physiological and psychoactive effects raise
      serious health implications with possible impact on athletes and doping
      practices. This new phenomenon needs to be thoroughly studied and monitored.

PMID- 29461476
TI  - Serve Size and Estimated Energy and Protein Contents of Meals Prepared by 'Meals
      on Wheels' South Australia Inc.: Findings from a Meal Audit Study.
AB  - An audit of 'standard' (STD) and 'energy and protein fortified' (HEHP) meals from
      Meals on Wheels (MOW) South Australia's summer menu was conducted to evaluate the
      consistency, and serve size and nutrient contents, of their menu items. Twenty
      soups, 20 mains and 20 desserts from each of the STD and HEHP menus were prepared
      at the MOW South Australia's kitchen and delivered to three 'sham(dummy)-clients'
      over a 5-week period. Each meal component was weighed in triplicate, to the
      nearest gram, the variation within the serve weight was calculated, and the
      overall energy and protein content of each meal was determined using FoodWorks
      (Xyris Software, Highgate Hill, Queensland, Australia). On average, the
      variability for soups and mains was <=6% and for desserts was <=10% and although
      the measured serve sizes of the MOW meals were consistently smaller than
      prescribed serve size, the differences were minor. As a percentage of recommended
      daily intakes (RDIs) for adults aged over 60 years, we calculated that the STD
      meals contained 21-39% for energy and 42-63% for protein while the HEHP meals
      contained 29-55% for energy and 46-69% for protein. These findings demonstrate
      that MOW meals currently meet the voluntary meal guidelines for energy and
      protein.

PMID- 29461478
TI  - Computational and Experimental Mechanical Modelling of a Composite Grouted Splice
      Sleeve Connector System.
AB  - Owing to its controllable tolerance, simple operation and no need for welding at
      construction site, the composite system involving grouted cement material, steel
      material and ductile iron material is widely used as grouted splice sleeve (GSS)
      connector for connecting precast concrete structures. However, the current design
      recommendations for such a composite connection system do not accurately account
      for its material nonlinearity behavior. In the present study, a three-dimensional
      nonlinear finite element model of a GSS connector is developed by considering the
      nonlinear material behavior of each component to fully investigate its mechanical
      performance under axial tension. To validate the proposed computational model and
      demonstrate the nonlinear response of the GSS connector, the pullout experimental
      test of two engineering specimens is carried out under monotonic tensile load,
      and a good agreement between the numerical and experimental test results is
      observed. Then, the sensitivity analysis of some controlling material properties
      and geometrical parameters is performed using the validated computational model
      to further understand the performance of such a composite structure in load
      carrying capacity and ductility of the connections to meet the rapid engineering
      applications of precast concrete structures.

PMID- 29461477
TI  - Anti-Renal Fibrotic Effect of Exercise Training in Hypertension.
AB  - The purpose of this study was to evaluate the effects of exercise training on
      renal fibrosis in hypertensive rats. Masson's trichrome staining and Western
      blotting were performed on the excised renal cortex from sixteen male
      spontaneously hypertensive rats (SHR), which were randomly divided into either a
      sedentary hypertensive group (SHR) or exercise hypertensive group (SHR-EX,
      running on an exercise treadmill for 60 min/day, 5 sessions/week, for 12 weeks),
      and from eight male Wistar-Kyoto rats which served as a sedentary normotensive
      group (WKY). The systolic blood pressure (SBP) and renal fibrosis in hypertensive
      rats improved after exercise training. The inflammatory-related protein levels of
      interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), as well as the fibrotic
      related protein levels of transforming growth factor-beta (TGF-beta), phospho
      Smad2/3 (p-Smad2/3), connective tissue growth factor (CTGF), matrix
      metalloproteinase-9 (MMP-9), and matrix metalloproteinase-2 (MMP-2) were
      decreased in the SHR-EX group when compared with the SHR group. Exercise training
      suppressed the hypertension-induced renal cortical inflammatory and fibrotic
      pathways in hypertensive rat models. These findings might indicate a new
      therapeutic effect for exercise training to prevent renal fibrosis in
      hypertensive nephropathy.

PMID- 29461480
TI  - Biocontrol of Fusarium graminearum sensu stricto, Reduction of Deoxynivalenol
      Accumulation and Phytohormone Induction by Two Selected Antagonists.
AB  - Fusarium head blight (FHB) is a devastating disease that causes extensive yield
      and quality losses to wheat and other small cereal grains worldwide. Species
      within the Fusarium graminearum complex are the main pathogens associated with
      the disease, F. graminearum sensu stricto being the main pathogen in Argentina.
      Biocontrol can be used as part of an integrated pest management strategy.
      Phytohormones play a key role in the plant defense system and their production
      can be induced by antagonistic microorganisms. The aims of this study were to
      evaluate the effect of the inoculation of Bacillus velezensis RC 218, F.
      graminearum and their co-inoculation on the production of salicylic acid (SA) and
      jasmonic acid (JA) in wheat spikes at different periods of time under greenhouse
      conditions, and to evaluate the effect of B. velezensis RC 218 and Streptomyces
      albidoflavus RC 87B on FHB disease incidence, severity and deoxynivalenol
      accumulation on Triticum turgidum L. var. durum under field conditions. Under
      greenhouse conditions the production of JA was induced after F. graminearum
      inoculation at 48 and 72 h, but JA levels were reduced in the co-inoculated
      treatments. No differences in JA or SA levels were observed between the B.
      velezensis treatment and the water control. In the spikes inoculated with F.
      graminearum, SA production was induced early (12 h), as it was shown for initial
      FHB basal resistance, while JA was induced at a later stage (48 h), revealing
      different defense strategies at different stages of infection by the
      hemibiotrophic pathogen F. graminearum. Both B. velezensis RC 218 and S.
      albidoflavus RC 87B effectively reduced FHB incidence (up to 30%), severity (up
      to 25%) and deoxynivalenol accumulation (up to 51%) on durum wheat under field
      conditions.

PMID- 29461479
TI  - Donor Human Milk Protects against Bronchopulmonary Dysplasia: A Systematic Review
      and Meta-Analysis.
AB  - Bronchopulmonary dysplasia (BPD) is the most common complication after preterm
      birth. Pasteurized donor human milk (DHM) has increasingly become the standard of
      care for very preterm infants over the use of preterm formula (PF) if the
      mother's own milk (MOM) is unavailable. Studies have reported beneficial effects
      of DHM on BPD. We conducted a systematic review and meta-analysis of randomized
      controlled trials (RCTs) and observational studies on the effects of DHM on BPD
      and other respiratory outcomes. Eighteen studies met the inclusion criteria. Meta
      analysis of RCTs could not demonstrate that supplementation of MOM with DHM
      reduced BPD when compared to PF (three studies, risk ratio (RR) 0.89, 95%
      confidence interval (CI) 0.60-1.32). However, meta-analysis of observational
      studies showed that DHM supplementation reduced BPD (8 studies, RR 0.78, 95% CI
      0.67-0.90). An exclusive human milk diet reduced the risk of BPD, compared to a
      diet with PF and/or bovine milk-based fortifier (three studies, RR 0.80, 95% CI
      0.68-0.95). Feeding raw MOM, compared to feeding pasteurized MOM, protected
      against BPD (two studies, RR 0.77, 95% CI 0.62-0.96). In conclusion, our data
      suggest that DHM protects against BPD in very preterm infants.

PMID- 29461481
TI  - A Dislocation-Scale Characterization of the Evolution of Deformation
      Microstructures around Nanoindentation Imprints in a TiAl Alloy.
AB  - In this work, plastic deformation was locally introduced at room temperature by
      nanoindentation on a gamma-TiAl-based alloy. Comprehensive analyses of
      microstructures were performed before and after deformation. In particular, the
      Burgers vectors, the line directions, and the mechanical twinning systems were
      studied via accurate electron channeling contrast imaging. Accommodation of the
      deformation are reported and a scenario is proposed. All features help to explain
      the poor ductility of the TiAl-based alloys at room temperature.

PMID- 29461482
TI  - Fiber Intake and Insulin Resistance in 6374 Adults: The Role of Abdominal
      Obesity.
AB  - A cross-sectional design was used to evaluate the relationship between fiber
      intake and insulin resistance, indexed using HOMA (homeostatic model assessment),
      in a National Health and Nutrition Examination Study (NHANES) sample of 6374 U.S.
      adults. Another purpose was to test the influence of covariates on the
      association. A third aim was to compare HOMA levels between two groups based on
      the recommended intake of 14 grams of fiber per 1000 kilocalories (kcal). Fiber
      intake was measured using a 24-hour recall. With demographic variables
      controlled, results showed that HOMA differed across High, Moderate, and Low
      fiber categories (F = 5.4, p = 0.0072). Adjusting for the demographic variables,
      the possible misreporting of energy intake, smoking, and physical activity
      strengthened the relationship (F = 8.0, p = 0.0009), which remained significant
      after adjusting for body fat (F = 7.0, p = 0.0019) and body mass index (BMI) (F =
      4.9, p = 0.0108), with the other covariates. However, the fiber-HOMA relationship
      was eliminated after adjusting for waist circumference (F = 2.3, p = 0.1050).
      Dividing participants based on the recommended 14-gram standard resulted in
      meaningful HOMA differences (F = 16.4, p = 0.0002), and the association was not
      eliminated after controlling for waist circumference. Apparently, adults with
      high fiber consumption have less insulin resistance than their counterparts.
      However, much of the association is due to differences in waist circumference,
      unless the recommended intake of fiber is attained.

PMID- 29461483
TI  - Influence of Iron Deficiency on HbA1c Levels in Pregnant Women: Comparison with
      Non-Pregnant Women.
AB  - Although HbA1c is widely used as a glycemic control indicator, HbA1c is known to
      show falsely high levels in patients in an iron deficient state (IDS). We
      compared the influence of IDS on HbA1c levels between pregnant women, due to
      mainly an increase in demand for iron without bleeding, and non-pregnant women,
      due to mainly bleeding (menstruation). We studied 42 non-diabetic pregnant women
      (pregnant group) and 42 age-matched non-pregnant women with normal glucose
      tolerance (non-pregnant group). We compared HbA1c and glycated albumin (GA)
      levels between IDS and normal iron state (NIS) in both groups. Furthermore, we
      analyzed the correlation between indicators of glycemic control and iron-related
      parameters [mean corpuscular hemoglobin, serum transferrin saturation (%Tf), and
      serum ferritin] in both groups. Compared with non-pregnant women, pregnant women
      had significantly lower %Tf and serum ferritin levels and significantly higher
      morbidity of IDS. HbA1c, but not GA, had significantly higher levels in pregnant
      women with IDS compared with NIS; however, HbA1c in non-pregnant women showed no
      significant difference for both IDS and NIS. In pregnant women, significant
      negative correlations were observed between HbA1c and iron-related parameters. In
      non-pregnant women, negative correlations were observed between HbA1c and these
      parameters, but they were not significant. No significant correlations were
      observed between GA and iron-related parameters in both groups. HbA1c levels in
      pregnant women were found to be largely affected by iron deficiency compared with
      non-pregnant women. For this reason, GA, which is not affected by iron
      deficiency, is desirable for use in the assessment of glycemic control during
      pregnancy.

PMID- 29461484
TI  - TiO2@PEI-Grafted-MWCNTs Hybrids Nanocomposites Catalysts for CO2 Photoreduction.
AB  - Anatase (TiO2) and multiwalled carbon nanotubes bearing polyethylenimine (PEI)
      anchored on their surface were hybridized in different proportions according to a
      sol-gel method. The resulting nanocomposites (TiO2@PEI-MWCNTs), characterized by
      BET, XRD, XPS, SEM, and UV techniques, were found efficient catalysts for CO2
      photoreduction into formic and acetic acids in water suspension and under visible
      light irradiation. PEI-grafted nanotubes co-catalysts are believed to act as CO2
      activators by forming a carbamate intermediate allowing to accomplish the first
      example in the literature of polyamines/nanotubes/TiO2 mediated CO2
      photoreduction to carboxylic acids.

PMID- 29461485
TI  - Surgical Considerations of Intractable Mesial Temporal Lobe Epilepsy.
AB  - Surgery of temporal lobe epilepsy is the best opportunity for seizure freedom in
      medically intractable patients. The surgical approach has evolved to recognize
      the paramount importance of the mesial temporal structures in the majority of
      patients with temporal lobe epilepsy who have a seizure origin in the mesial
      temporal structures. For those individuals with medically intractable mesial
      temporal lobe epilepsy, a selective amygdalohippocampectomy surgery can be done
      that provides an excellent opportunity for seizure freedom and limits the
      resection to temporal lobe structures primarily involved in seizure genesis.

PMID- 29461486
TI  - From Prenatal to Preimplantation Genetic Diagnosis of beta-Thalassemia.
      Prevention Model in 8748 Cases: 40 Years of Single Center Experience.
AB  - The incidence of beta-thalassemia in Sardinia is high and beta-39 is the most
      common mutation. The prevention campaign started in 1977 and was performed in a
      single center (Microcitemico Hospital, Cagliari, Sardinia, Italy). It was based
      on educational programs, population screening by hematological and molecular
      identification of the carriers. Prenatal and pre-implantation diagnosis was
      offered to couples at risk. 8564 fetal diagnosis procedures using different
      invasive approaches and analysis techniques were performed in the last 40 years.
      Trans-abdominal chorionic villous sampling was preferred due to lower
      complication risks and early diagnosis. Chorionic villous DNA was analyzed by PCR
      technique. 2138 fetuses affected by beta-thalassemia were diagnosed. Women opted
      for termination of the pregnancy (TOP) in 98.2% of these cases. Pre-implantation
      genetic diagnosis (PGD) was proposed to couples at risk to avoid TOP. A total of
      184 PGD were performed. Initially, the procedure was exclusively offered to
      infertile couples, according to the law in force. The success rate of pregnancies
      increased from 11.1% to 30.8% when, crucial law changes were enacted, and PGD was
      offered to fertile women as well. Forty years of beta-thalassemia prevention
      programs in Sardinia have demonstrated the important decrease of this severe
      genetic disorder.

PMID- 29461487
TI  - Understanding the Role of Negative Emotions in Adult Learning and Achievement: A
      Social Functional Perspective.
AB  - The role of emotions in adult learning and achievement has received increasing
      attention in recent years. However, much of the emphasis has been on test
      anxiety, rather than the wider spectrum of negative emotions such as sadness,
      grief, boredom and anger. This paper reports findings of a qualitative study
      exploring the experience and functionality of negative emotions at university.
      Thirty-six academic staff and students from an Australian university were
      interviewed about emotional responses to a range of learning events. Data
      analysis was informed by a prototype approach to emotion research. Four
      categories of discrete negative emotions (anger, sadness, fear, boredom) were
      considered by teachers and students to be especially salient in learning, with
      self-conscious emotions (guilt, embarrassment, shame) mentioned by more students
      than staff. While negative emotions were frequently viewed as detrimental to
      motivation, performance and learning, they were also construed under some
      circumstances as beneficial. The findings are discussed in relation to the value
      of social functional approaches for a better understanding of the diverse roles
      of negative emotions in learning and achievement.

PMID- 29461488
TI  - Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity Is
      Decreased in Multiple Sclerosis Patients: Effects of beta-Interferon Treatment.
AB  - OBJECTIVES: Evidence of mitochondrial respiratory chain (MRC) dysfunction and
      oxidative stress has been implicated in the pathophysiology of multiple sclerosis
      (MS). However, at present, there is no reliable low invasive surrogate available
      to evaluate mitochondrial function in these patients. In view of the particular
      sensitivity of MRC complex IV to oxidative stress, the aim of this study was to
      assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and
      compare these results to age matched controls and MS patients on beta-interferon
      treatment. METHODS: Spectrophotometric enzyme assay was employed to measure MRC
      complex IV activity in blood mononuclear cell obtained multiple sclerosis
      patients and aged matched controls. RESULTS: MRC Complex IV activity was found to
      be significantly decreased (p < 0.05) in MS patients (2.1 +/- 0.8 k/nmol * 10-3;
      mean +/- SD] when compared to the controls (7.2 +/- 2.3 k/nmol * 10-3). Complex
      IV activity in MS patients on beta-interferon (4.9 +/- 1.5 k/nmol * 10-3) was not
      found to be significantly different from that of the controls. CONCLUSIONS: This
      study has indicated evidence of peripheral MRC complex IV deficiency in MS
      patients and has highlighted the potential utility of BMNCs as a potential means
      to evaluate mitochondrial function in this disorder. Furthermore, the reported
      improvement of complex IV activity may provide novel insights into the mode(s) of
      action of beta-interferon.

PMID- 29461489
TI  - A Model-Driven Co-Design Framework for Fusing Control and Scheduling Viewpoints.
AB  - Model-Driven Engineering (MDE) is widely applied in the industry to develop new
      software functions and integrate them into the existing run-time environment of a
      Cyber-Physical System (CPS). The design of a software component involves
      designers from various viewpoints such as control theory, software engineering,
      safety, etc. In practice, while a designer from one discipline focuses on the
      core aspects of his field (for instance, a control engineer concentrates on
      designing a stable controller), he neglects or considers less importantly the
      other engineering aspects (for instance, real-time software engineering or energy
      efficiency). This may cause some of the functional and non-functional
      requirements not to be met satisfactorily. In this work, we present a co-design
      framework based on timing tolerance contract to address such design gaps between
      control and real-time software engineering. The framework consists of three
      steps: controller design, verified by jitter margin analysis along with co
      simulation, software design verified by a novel schedulability analysis, and the
      run-time verification by monitoring the execution of the models on target. This
      framework builds on CPAL (Cyber-Physical Action Language), an MDE design
      environment based on model-interpretation, which enforces a timing-realistic
      behavior in simulation through timing and scheduling annotations. The application
      of our framework is exemplified in the design of an automotive cruise control
      system.

PMID- 29461490
TI  - PS, It's Complicated: The Roles of Phosphatidylserine and
      Phosphatidylethanolamine in the Pathogenesis of Candida albicans and Other
      Microbial Pathogens.
AB  - The phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE) play
      important roles in the virulence of Candida albicans and loss of PS synthesis or
      synthesis of PE from PS (PS decarboxylase) severely compromises virulence in C.
      albicans in a mouse model of systemic candidiasis. This review discusses
      synthesis of PE and PS in C. albicans and mechanisms by which these lipids impact
      virulence in this fungus. This is further compared to how PS and PE synthesis
      impact virulence in other fungi, parasites and bacteria. Furthermore, the impact
      of PS asymmetry on virulence and extracellular vesicle formation in several
      microbes is reviewed. Finally, the potential for PS and PE synthases as drug
      targets in these various kingdoms is also examined.

PMID- 29461492
TI  - Layup Configuration Effect on Notch Residual Strength in Composite Laminates.
AB  - The current trend shows an increasing demand for composites due to their high
      stiffness to weight ratio and the recent progress in manufacturing and cost
      reduction of composites. To combine high strength and stiffness in a cost
      effective way, composites are often joined with steel or aluminum. However,
      joining of thermoset composite materials is challenging because circular holes
      are often used to join them with their metal counterparts. These design based
      circular holes induce high stress concentration around the hole. The purpose of
      this paper is to focus on layup configuration and its impact on notch stress
      distribution. To ensure high quality and uniformity, the holes were machined by a
      5 kW continuous wave (cw) CO2 laser. The stress distribution was evaluated and
      compared by using finite element analysis and Lekhnitskii's equations. For
      further understanding, the notch strength of the laminates was compared and
      strain distributions were analyzed using the digital image correlation technique.

PMID- 29461493
TI  - Design and Implementation of e-Health System Based on Semantic Sensor Network
      Using IETF YANG.
AB  - Recently, healthcare services can be delivered effectively to patients anytime
      and anywhere using e-Health systems. e-Health systems are developed through
      Information and Communication Technologies (ICT) that involve sensors, mobiles,
      and web-based applications for the delivery of healthcare services and
      information. Remote healthcare is an important purpose of the e-Health system.
      Usually, the eHealth system includes heterogeneous sensors from diverse
      manufacturers producing data in different formats. Device interoperability and
      data normalization is a challenging task that needs research attention. Several
      solutions are proposed in the literature based on manual interpretation through
      explicit programming. However, programmatically implementing the interpretation
      of the data sender and data receiver in the e-Health system for the data
      transmission is counterproductive as modification will be required for each new
      device added into the system. In this paper, an e-Health system with the Semantic
      Sensor Network (SSN) is proposed to address the device interoperability issue. In
      the proposed system, we have used IETF YANG for modeling the semantic e-Health
      data to represent the information of e-Health sensors. This modeling scheme helps
      in provisioning semantic interoperability between devices and expressing the
      sensing data in a user-friendly manner. For this purpose, we have developed an
      ontology for e-Health data that supports different styles of data formats. The
      ontology is defined in YANG for provisioning semantic interpretation of sensing
      data in the system by constructing meta-models of e-Health sensors. The proposed
      approach assists in the auto-configuration of eHealth sensors and querying the
      sensor network with semantic interoperability support for the e-Health system.

PMID- 29461491
TI  - Cancer Stem Cells, Bone and Tumor Microenvironment: Key Players in Bone
      Metastases.
AB  - Tumor mass is constituted by a heterogeneous group of cells, among which a key
      role is played by the cancer stem cells (CSCs), possessing high regenerative
      properties. CSCs directly metastasize to bone, since bone microenvironment
      represents a fertile environment that protects CSCs against the immune system,
      and maintains their properties and plasticity. CSCs can migrate from the primary
      tumor to the bone marrow (BM), due to their capacity to perform the epithelial-to
      mesenchymal transition. Once in BM, they can also perform the mesenchymal-to
      epithelial transition, allowing them to proliferate and initiate bone lesions.
      Another factor explaining the osteotropism of CSCs is their ability to recognize
      chemokine gradients toward BM, through the CXCL12-CXCR4 axis, also known to be
      involved in tumor metastasis to other organs. Moreover, the expression of CXCR4
      is associated with the maintenance of CSCs' stemness, and CXCL12 expression by
      osteoblasts attracts CSCs to the BM niches. CSCs localize in the pre-metastatic
      niches, which are anatomically distinct regions within the tumor microenvironment
      and govern the metastatic progression. According to the stimuli received in the
      niches, CSCs can remain dormant for long time or outgrow from dormancy and create
      bone lesions. This review resumes different aspects of the CSCs' bone metastastic
      process and discusses available treatments to target CSCs.

PMID- 29461495
TI  - An Innovative Approach to Control Steel Reinforcement Corrosion by Self-Healing.
AB  - The corrosion of reinforced steel, and subsequent reinforced concrete
      degradation, is a major concern for infrastructure durability. New materials with
      specific, tailor-made properties or the establishment of optimum construction
      regimes are among the many approaches to improving civil structure performance.
      Ideally, novel materials would carry self-repairing or self-healing capacities,
      triggered in the event of detrimental influence and/or damage. Controlling or
      altering a material's behavior at the nano-level would result in traditional
      materials with radically enhanced properties. Nevertheless, nanotechnology
      applications are still rare in construction, and would break new ground in
      engineering practice. An approach to controlling the corrosion-related
      degradation of reinforced concrete was designed as a synergetic action of
      electrochemistry, cement chemistry and nanotechnology. This contribution presents
      the concept of the approach, namely to simultaneously achieve steel corrosion
      resistance and improved bulk matrix properties. The technical background and
      challenges for the application of polymeric nanomaterials in the field are
      briefly outlined in view of this concept, which has the added value of self
      healing. The credibility of the approach is discussed with reference to
      previously reported outcomes, and is illustrated via the results of the steel
      electrochemical responses and microscopic evaluations of the discussed materials.

PMID- 29461494
TI  - Less Waste on Waist Measurements: Determination of Optimal Waist Circumference
      Measurement Site to Predict Visceral Adipose Tissue in Postmenopausal Women with
      Obesity.
AB  - With obesity being a leading cause of preventable death, it is vital to
      understand how best to identify individuals with greater risk of metabolic
      disease, especially those with high visceral adipose tissue (VAT). This study
      aimed to determine whether three commonly used waist circumference (WC)
      measurement sites could provide accurate estimations of VAT, as determined by
      magnetic resonance imaging (MRI), which is a gold standard for measuring VAT, in
      postmenopausal women with obesity. VAT volume was measured by MRI of the total
      abdomen in 97 women aged 57.7 +/- 0.4 years (mean +/- SEM), mean body mass index
      34.5 +/- 0.2 kg/m2. WC was measured at the midpoint between the lowest rib and
      the iliac crest (WCmid), the narrowest point of the torso (WCnarrow), and at the
      level of the umbilicus (WCumbilicus). WC differed significantly according to
      measurement site, with WCnarrow (102.1 +/- 0.7 cm) < WCmid (108.3 +/- 0.7 cm) <
      WCumbilicus (115.7 +/- 0.8 cm) (p < 0.001). WCmid, WCnarrow and WCumbilicus were
      all significantly correlated with VAT, as measured by MRI (r = 0.581, 0.563 and
      0.390, respectively; p < 0.001 for all), but the relationships between WCmid or
      WCnarrow and VAT determined by MRI were stronger than for WCumbilicus.
      Measurement of either WCmid or WCnarrow provides valid estimates of VAT in
      postmenopausal women with obesity, with WCnarrow being favoured in light of its
      greater ease and speed of measurement in this population.

PMID- 29461496
TI  - Online Aerial Terrain Mapping for Ground Robot Navigation.
AB  - This work presents a collaborative unmanned aerial and ground vehicle system
      which utilizes the aerial vehicle's overhead view to inform the ground vehicle's
      path planning in real time. The aerial vehicle acquires imagery which is
      assembled into a orthomosaic and then classified. These terrain classes are used
      to estimate relative navigation costs for the ground vehicle so energy-efficient
      paths may be generated and then executed. The two vehicles are registered in a
      common coordinate frame using a real-time kinematic global positioning system
      (RTK GPS) and all image processing is performed onboard the unmanned aerial
      vehicle, which minimizes the data exchanged between the vehicles. This paper
      describes the architecture of the system and quantifies the registration errors
      between the vehicles.

PMID- 29461497
TI  - Pediatric Palliative Care for Children with Progressive Non-Malignant Diseases.
AB  - A substantial number of children cared for by pediatric palliative care
      physicians have progressive non-malignant conditions. Some elements of their care
      overlap with care for children with cancer while other elements, especially
      prognosis and trajectory, have nuanced differences. This article reviews the
      population, physical-emotional and social concerns, and trajectory.

PMID- 29461498
TI  - Qualitative and Quantitative Phytochemical Analysis of Different Extracts from
      Thymus algeriensis Aerial Parts.
AB  - This study was performed to evaluate the metabolite recovery from different
      extraction methods applied to Thymusalgeriensis aerial parts. A high-performance
      liquid chromatographic method using photodiode array detector with gradient
      elution has been developed and validated for the simultaneous estimation of
      different phenolic compounds in the extracts and in their corresponding purified
      fractions. The experimental results show that microwave-assisted aqueous
      extraction for 15 min at 100  degrees C gave the most phenolics-enriched extract,
      reducing extraction time without degradation effects on bioactives. Sixteen
      compounds were identified in this extract, 11 phenolic compounds and five
      flavonoids, all known for their biological activities. Color analysis and
      determination of chlorophylls and carotenoids implemented the knowledge of the
      chemical profile of this plant.

PMID- 29461499
TI  - Pilot Testing a Photo-Based Food Diary in Nine- to Twelve- Year Old- Children
      from Dunedin, New Zealand.
AB  - The purpose of the study was to investigate if an Evernote app-based electronic
      food diary is an acceptable method to measure nutrient intake in children aged 9
      12 years. A convenience sample of 16 nine- to twelve-year-olds from Dunedin, New
      Zealand, completed a paper-based food dairy on four days, followed by four more
      days using a photo-based diary on an iPod. This photo-based diary used a
      combination of photographs and short written descriptions of foods consumed. The
      photo-based diaries produced similar results to written diaries for all
      macronutrients and major micronutrients (e.g., calcium, fibre, vitamin C).
      Spearman correlation coefficients between the two methods for all nutrients,
      except sugars, were above 0.3. However, burden on researchers and participants
      was reduced for the photo-based diary, primarily due to the additional
      information obtained from photographs. Participating children needed less help
      from parents with completing the electronic diaries and preferred them to the
      paper version. This electronic diary is likely to be suitable, after additional
      formal validity testing, for use in measuring nutrient intake in children.

PMID- 29461500
TI  - Diverse and Abundant Secondary Metabolism Biosynthetic Gene Clusters in the
      Genomes of Marine Sponge Derived Streptomyces spp. Isolates.
AB  - The genus Streptomyces produces secondary metabolic compounds that are rich in
      biological activity. Many of these compounds are genetically encoded by large
      secondary metabolism biosynthetic gene clusters (smBGCs) such as polyketide
      synthases (PKS) and non-ribosomal peptide synthetases (NRPS) which are modular
      and can be highly repetitive. Due to the repeats, these gene clusters can be
      difficult to resolve using short read next generation datasets and are often
      quite poorly predicted using standard approaches. We have sequenced the genomes
      of 13 Streptomyces spp. strains isolated from shallow water and deep-sea sponges
      that display antimicrobial activities against a number of clinically relevant
      bacterial and yeast species. Draft genomes have been assembled and smBGCs have
      been identified using the antiSMASH (antibiotics and Secondary Metabolite
      Analysis Shell) web platform. We have compared the smBGCs amongst strains in the
      search for novel sequences conferring the potential to produce novel bioactive
      secondary metabolites. The strains in this study recruit to four distinct clades
      within the genus Streptomyces. The marine strains host abundant smBGCs which
      encode polyketides, NRPS, siderophores, bacteriocins and lantipeptides. The deep
      sea strains appear to be enriched with gene clusters encoding NRPS. Marine
      adaptations are evident in the sponge-derived strains which are enriched for
      genes involved in the biosynthesis and transport of compatible solutes and for
      heat-shock proteins. Streptomyces spp. from marine environments are a promising
      source of novel bioactive secondary metabolites as the abundance and diversity of
      smBGCs show high degrees of novelty. Sponge derived Streptomyces spp. isolates
      appear to display genomic adaptations to marine living when compared to
      terrestrial strains.

PMID- 29461502
TI  - Exploring 3D Human Action Recognition: from Offline to Online.
AB  - With the introduction of cost-effective depth sensors, a tremendous amount of
      research has been devoted to studying human action recognition using 3D motion
      data. However, most existing methods work in an offline fashion, i.e., they
      operate on a segmented sequence. There are a few methods specifically designed
      for online action recognition, which continually predicts action labels as a
      stream sequence proceeds. In view of this fact, we propose a question: can we
      draw inspirations and borrow techniques or descriptors from existing offline
      methods, and then apply these to online action recognition? Note that extending
      offline techniques or descriptors to online applications is not straightforward,
      since at least two problems-including real-time performance and sequence
      segmentation-are usually not considered in offline action recognition. In this
      paper, we give a positive answer to the question. To develop applicable online
      action recognition methods, we carefully explore feature extraction, sequence
      segmentation, computational costs, and classifier selection. The effectiveness of
      the developed methods is validated on the MSR 3D Online Action dataset and the
      MSR Daily Activity 3D dataset.

PMID- 29461501
TI  - First Report on Chitin in a Non-Verongiid Marine Demosponge: The Mycale
      euplectellioides Case.
AB  - Sponges (Porifera) are recognized as aquatic multicellular organisms which
      developed an effective biochemical pathway over millions of years of evolution to
      produce both biologically active secondary metabolites and biopolymer-based
      skeletal structures. Among marine demosponges, only representatives of the
      Verongiida order are known to synthetize biologically active substances as well
      as skeletons made of structural polysaccharide chitin. The unique three
      dimensional (3D) architecture of such chitinous skeletons opens the widow for
      their recent applications as adsorbents, as well as scaffolds for tissue
      engineering and biomimetics. This study has the ambitious goal of monitoring
      other orders beyond Verongiida demosponges and finding alternative sources of
      naturally prestructured chitinous scaffolds; especially in those demosponge
      species which can be cultivated at large scales using marine farming conditions.
      Special attention has been paid to the demosponge Mycale
      euplectellioides(Heteroscleromorpha: Poecilosclerida: Mycalidae) collected in the
      Red Sea. For the first time, we present here a detailed study of the isolation of
      chitin from the skeleton of this sponge, as well as its identification using
      diverse bioanalytical tools. Calcofluor white staining, Fourier-transform
      Infrared Spcetcroscopy (FTIR), electrospray ionization mass spectrometry (ESI
      MS), scanning electron microscopy (SEM), and fluorescence microscopy, as well as
      a chitinase digestion assay were applied in order to confirm with strong evidence
      the finding of a-chitin in the skeleton of M. euplectellioides. We suggest that
      the discovery of chitin within representatives of the Mycale genus is a promising
      step in their evaluation of these globally distributed sponges as new renewable
      sources for both biologically active metabolites and chitin, which are of
      prospective use for pharmacology and biomaterials oriented biomedicine,
      respectively.

PMID- 29461503
TI  - Improved Syntheses of the Mglu5 Antagonists MMPEP and MTEP Using Sonogashira
      Cross-Coupling.
AB  - The Sonogashira cross-coupling, a key step in the syntheses of the mGlu5
      antagonists MMPEP and MTEP, provided an improved three-step method for the
      preparation of MMPEP in 62% overall yield. Using Spartan molecular modeling kit
      an explanation for the failure to employ analogues method in the synthesis of
      MTEP was sought. The DFT calculations indicated that meaningful isolated yields
      were obtained when the HOMO energy of the aryl halide was lower than the HOMO
      energy of the respective alkyne.

PMID- 29461504
TI  - Examining Differential Resilience Mechanisms by Comparing 'Tipping Points' of the
      Effects of Neighborhood Conditions on Anxiety by Race/Ethnicity.
AB  - Exposure to adverse environmental and social conditions affects physical and
      mental health through complex mechanisms. Different racial/ethnic (R/E) groups
      may be more or less vulnerable to the same conditions, and the resilience
      mechanisms that can protect them likely operate differently in each population.
      We investigate how adverse neighborhood conditions (neighborhood disorder, NDis)
      differentially impact mental health (anxiety, Anx) in a sample of white and Black
      (African American) young women from Southeast Texas, USA. We illustrate a simple
      yet underutilized segmented regression model where linearity is relaxed to allow
      for a shift in the strength of the effect with the levels of the predictor. We
      compare how these effects change within R/E groups with the level of the
      predictor, but also how the "tipping points," where the effects change in
      strength, may differ by R/E. We find with classic linear regression that
      neighborhood disorder adversely affects Black women's anxiety, while in white
      women the effect seems negligible. Segmented regressions show that the Ndis ->
      Anx effects in both groups of women appear to shift at similar levels, about one
      fifth of a standard deviation below the mean of NDis, but the effect for Black
      women appears to start out as negative, then shifts in sign, i.e., to increase
      anxiety, while for white women, the opposite pattern emerges. Our findings can
      aid in devising better strategies for reducing health disparities that take into
      account different coping or resilience mechanisms operating differentially at
      distinct levels of adversity. We recommend that researchers investigate when
      adversity becomes exceedingly harmful and whether this happens differentially in
      distinct populations, so that intervention policies can be planned to reverse
      conditions that are more amenable to change, in effect pushing back the overall
      social risk factors below such tipping points.

PMID- 29461506
TI  - Investigation of Sensitivities and Drift Effects of the Arrayed Flexible Chloride
      Sensor Based on RuO2/GO at Different Temperatures.
AB  - We investigate the temperature effect on sensing characteristics and drift effect
      of an arrayed flexible ruthenium dioxide (RuO2)/graphene oxide (GO) chloride
      sensor at different solution temperatures between 10  degrees C and 50  degrees
      C. The average sensor sensitivities according to our experimental results were
      28.2 +/- 1.4 mV/pCl (10  degrees C), 42.5 +/- 2.0 mV/pCl (20  degrees C), 47.1 +/
      1.8 mV/pCl (30  degrees C), 54.1 +/- 2.01 mV/pCl (40  degrees C) and 46.6 +/-
      2.1 mV/pCl (50  degrees C). We found the drift effects of an arrayed flexible
      RuO2/GO chloride sensor in a 1 M NaCl solution to be between 8.2 mV/h and 2.5
      mV/h with solution temperatures from 10  degrees C to 50  degrees C.

PMID- 29461505
TI  - Exopolysaccharides from Marine and Marine Extremophilic Bacteria: Structures,
      Properties, Ecological Roles and Applications.
AB  - The marine environment is the largest aquatic ecosystem on Earth and it harbours
      microorganisms responsible for more than 50% of total biomass of prokaryotes in
      the world. All these microorganisms produce extracellular polymers that
      constitute a substantial part of the dissolved organic carbon, often in the form
      of exopolysaccharides (EPS). In addition, the production of these polymers is
      often correlated to the establishment of the biofilm growth mode, during which
      they are important matrix components. Their functions include adhesion and
      colonization of surfaces, protection of the bacterial cells and support for
      biochemical interactions between the bacteria and the surrounding environment.
      The aim of this review is to present a summary of the status of the research
      about the structures of exopolysaccharides from marine bacteria, including
      capsular, medium released and biofilm embedded polysaccharides. Moreover,
      ecological roles of these polymers, especially for those isolated from extreme
      ecological niches (deep-sea hydrothermal vents, polar regions, hypersaline ponds,
      etc.), are reported. Finally, relationships between the structure and the
      function of the exopolysaccharides are discussed.

PMID- 29461507
TI  - Exploring the Metabolism of (+)-[18F]Flubatine in Vitro and in Vivo: LC-MS/MS
      Aided Identification of Radiometabolites in a Clinical PET Study.
AB  - Both (+)-[18F]flubatine and its enantiomer (-)-[18F]flubatine are radioligands
      for the neuroimaging of alpha4beta2 nicotinic acetylcholine receptors (nAChRs) by
      positron emission tomography (PET). In a clinical study in patients with early
      Alzheimer's disease, (+)-[18F]flubatine ((+)-[18F]1) was examined regarding its
      metabolic fate, in particular by identification of degradation products detected
      in plasma and urine. The investigations included an in vivo study of (+)
      flubatine ((+)-1) in pigs and structural elucidation of formed metabolites by LC
      MS/MS. Incubations of (+)-1 and (+)-[18F]1 with human liver microsomes were
      performed to generate in vitro metabolites, as well as radiometabolites, which
      enabled an assignment of their structures by comparison of LC-MS/MS and radio
      HPLC data. Plasma and urine samples taken after administration of (+)-[18F]1 in
      humans were examined by radio-HPLC and, on the basis of results obtained in vitro
      and in vivo, formed radiometabolites were identified.

PMID- 29461508
TI  - Radical Polymerization of Alkyl 2-Cyanoacrylates.
AB  - Cyanoacrylates (CAs) are well-known fast-setting adhesives, which are sold as
      liquids in the presence of stabilizers. Rapid anionic polymerization on exposure
      to surface moisture is responsible for instant adhesion. The more difficult, but
      synthetically more useful radical polymerization is only possible under acidic
      conditions. Recommendations on the handling of CAs and the resulting polymers are
      provided herein. In this review article, after a general description of monomer
      and polymer properties, radical homo- and copolymerization studies are described,
      along with an overview of nanoparticle preparations. A summary of our recently
      reported radical polymerization of CAs, using reversible addition-fragmentation
      chain transfer (RAFT) polymerization, is provided.

PMID- 29461509
TI  - A Brief Note on the Magnetowetting of Magnetic Nanofluids on AAO Surfaces.
AB  - In magnetowetting, the material properties of liquid, surface morphology of
      solid, and applied external field are three major factors used to determine the
      wettability of a liquid droplet on a surface. For wetting measurements, an
      irregular or uneven surface could result in a significant experimental
      uncertainty. The periodic array with a hexagonal symmetry structure is an
      advantage of the anodic aluminum oxide (AAO) structure. This study presents the
      results of the wetting properties of magnetic nanofluid sessile droplets on
      surfaces of various AAO pore sizes under an applied external magnetic field.
      Stable, water-based magnetite nanofluids are prepared by combining the chemical
      co-precipitation with the sol-gel technique, and AAO surfaces are then generated
      by anodizing the aluminum sheet in the beginning. The influence of pore size and
      magnetic field gradient on the magnetowetting of magnetic nanofluids on AAO
      surfaces is then investigated by an optical test system. Experimental results
      show that increasing the processing voltage of AAO templates could result in
      enhanced non-wettability behavior; that is, the increase in AAO pore size could
      lead to the increase in contact angle. The contact angle could be reduced by the
      applied magnetic field gradient. In general, the magnetic field has a more
      significant effect at smaller AAO pore sizes.

PMID- 29461510
TI  - Genetic Variation and Hybridisation among Eight Species of kowhai (Sophora:
      Fabaceae) from New Zealand Revealed by Microsatellite Markers.
AB  - We analysed nine microsatellite markers for 626 individuals representing the
      geographic range of eight closely related endemic New Zealand species of Sophora.
      Structure analysis identified the optimal K value as seven, with samples
      identified as Sophorachathamica, Sophorafulvida, Sophoralongicarinata, and
      Sophoraprostrata retrieved as well-defined groups. The remaining samples formed
      less resolved groups referable to Sophoratetraptera and Sophoragodleyi, with
      Sophoramicrophylla and Sophoramolloyi forming the seventh group. Our data suggest
      that considerable admixture occurs and this is most likely the result of
      hybridisation or introgression. S.fulvida shows admixture with the sympatric
      S.chathamica, and the widespread S.microphylla exhibits admixture with the
      sympatric S.godleyi, S.molloyi, and S.tetraptera.

PMID- 29461512
TI  - Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant
      Mutations in GJA8 in Pakistani Congenital Cataract Families.
AB  - Congenital cataract is a clinically and genetically heterogeneous disease. The
      present study was undertaken to find the genetic cause of congenital cataract
      families. DNA samples of a large consanguineous Pakistani family were genotyped
      with a high resolution single nucleotide polymorphism Illumina microarray.
      Homozygosity mapping identified a homozygous region of 4.4 Mb encompassing the
      gene GJA3. Sanger sequence analysis of the GJA3 gene revealed a novel homozygous
      variant c.950dup p.(His318ProfsX8) segregating in an autosomal recessive (AR)
      manner. The previously known mode of inheritance for GJA3 gene mutations in
      cataract was autosomal dominant (AD) only. The screening of additional probands
      (n = 41) of cataract families revealed a previously known mutation c.56C>T
      p.(Thr19Met) in GJA3 gene. In addition, sequencing of the exon-intron boundaries
      of the GJA8 gene in 41 cataract probands revealed two additional mutations: a
      novel c.53C>T p.(Ser18Phe) and a known c.175C>G p.(Pro59Ala) mutation, both co
      segregating with the disease phenotype in an AD manner. All these mutations are
      predicted to be pathogenic by in silico analysis and were absent in the control
      databases. In conclusion, results of the current study enhance our understanding
      of the genetic basis of cataract, and identified the involvement of the GJA3 in
      the disease etiology in both AR and AD manners.

PMID- 29461513
TI  - Inter-comparison of multiple statistically downscaled climate datasets for the
      Pacific Northwest, USA.
AB  - Statistically downscaled climate data have been widely used to explore possible
      impacts of climate change in various fields of study. Although many studies have
      focused on characterizing differences in the downscaling methods, few studies
      have evaluated actual downscaled datasets being distributed publicly. Spatially
      focusing on the Pacific Northwest, we compare five statistically downscaled
      climate datasets distributed publicly in the US: ClimateNA, NASA NEX-DCP30,
      MACAv2-METDATA, MACAv2-LIVNEH and WorldClim. We compare the downscaled
      projections of climate change, and the associated observational data used as
      training data for downscaling. We map and quantify the variability among the
      datasets and characterize the spatio-temporal patterns of agreement and
      disagreement among the datasets. Pair-wise comparisons of datasets identify the
      coast and high-elevation areas as areas of disagreement for temperature. For
      precipitation, high-elevation areas, rainshadows and the dry, eastern portion of
      the study area have high dissimilarity among the datasets. By spatially
      aggregating the variability measures into watersheds, we develop guidance for
      selecting datasets within the Pacific Northwest climate change impact studies.

PMID- 29461511
TI  - Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular
      System.
AB  - A-kinase anchoring proteins (AKAPs) and cyclic nucleotide phosphodiesterases
      (PDEs) are essential enzymes in the cyclic adenosine 3'-5' monophosphate (cAMP)
      signaling cascade. They establish local cAMP pools by controlling the intensity,
      duration and compartmentalization of cyclic nucleotide-dependent signaling.
      Various members of the AKAP and PDE families are expressed in the cardiovascular
      system and direct important processes maintaining homeostatic functioning of the
      heart and vasculature, e.g., the endothelial barrier function and excitation
      contraction coupling. Dysregulation of AKAP and PDE function is associated with
      pathophysiological conditions in the cardiovascular system including heart
      failure, hypertension and atherosclerosis. A number of diseases, including
      autosomal dominant hypertension with brachydactyly (HTNB) and type I long-QT
      syndrome (LQT1), result from mutations in genes encoding for distinct members of
      the two classes of enzymes. This review provides an overview over the AKAPs and
      PDEs relevant for cAMP compartmentalization in the heart and vasculature and
      discusses their pathophysiological role as well as highlights the potential
      benefits of targeting these proteins and their protein-protein interactions for
      the treatment of cardiovascular diseases.

PMID- 29461515
TI  - Epidemiological characteristics of human-infective RNA viruses.
AB  - RNA viruses are a major threat to human health. Here, based on extensive
      literature searches carried out over a period of 18 years, we provide a catalogue
      of all 214 known human-infective RNA virus species. We link these viruses to
      metadata for a number of traits that influence their epidemiology, including the
      date of the first report of human infection, transmissibility in human
      populations, transmission route(s) and host range. This database can be used in
      comparative studies of human-infective RNA viruses to identify the
      characteristics of viruses most likely to pose the greatest public health threat,
      both now and in the future.

PMID- 29461514
TI  - A large, open source dataset of stroke anatomical brain images and manual lesion
      segmentations.
AB  - Stroke is the leading cause of adult disability worldwide, with up to two-thirds
      of individuals experiencing long-term disabilities. Large-scale neuroimaging
      studies have shown promise in identifying robust biomarkers (e.g., measures of
      brain structure) of long-term stroke recovery following rehabilitation. However,
      analyzing large rehabilitation-related datasets is problematic due to barriers in
      accurate stroke lesion segmentation. Manually-traced lesions are currently the
      gold standard for lesion segmentation on T1-weighted MRIs, but are labor
      intensive and require anatomical expertise. While algorithms have been developed
      to automate this process, the results often lack accuracy. Newer algorithms that
      employ machine-learning techniques are promising, yet these require large
      training datasets to optimize performance. Here we present ATLAS (Anatomical
      Tracings of Lesions After Stroke), an open-source dataset of 304 T1-weighted MRIs
      with manually segmented lesions and metadata. This large, diverse dataset can be
      used to train and test lesion segmentation algorithms and provides a standardized
      dataset for comparing the performance of different segmentation methods. We hope
      ATLAS release 1.1 will be a useful resource to assess and improve the accuracy of
      current lesion segmentation methods.

PMID- 29461517
TI  - Arthropods dataset from different genetically modified maize events and
      associated controls.
AB  - Arthropods from four genetically modified (GM) maize hybrids (coleopteran
      resistant, coleopteran and lepidopteran resistant, lepidopteran
      resistant+herbicide tolerant and coleopteran resistant and herbicide tolerant)
      and non-GM varieties were sampled during a two-year field assessment. A total
      number of 363 555 arthropod individuals were collected. This represents the most
      comprehensive arthropod dataset from GM maize, and together with weed data, is
      reasonable to determine functional groups of arthropods and interactions between
      species. Trophic groups identified from both phytophagous and predatory
      arthropods were previously considered non-target organisms on which possible
      detrimental effects of Bacillus thuringiensis (Bt) toxins may have been directly
      (phytophagous species) or indirectly (predators) detected. The high number of
      individuals and species and their dynamics through the maize growing season can
      predict that interactions are highly correlational, and can thus be considered a
      useful tool to assess potential deleterious effects of Bt toxins on non-target
      organisms, serving to develop biosafety risk hypotheses for invertebrates exposed
      to GM maize plants.

PMID- 29461516
TI  - A database of chlorophyll a in Australian waters.
AB  - Chlorophyll a is the most commonly used indicator of phytoplankton biomass in the
      marine environment. It is relatively simple and cost effective to measure when
      compared to phytoplankton abundance and is thus routinely included in many
      surveys. Here we collate 173, 333 records of chlorophyll a collected since 1965
      from Australian waters gathered from researchers on regular coastal monitoring
      surveys and ocean voyages into a single repository. This dataset includes the
      chlorophyll a values as measured from samples analysed using spectrophotometry,
      fluorometry and high performance liquid chromatography (HPLC). The Australian
      Chlorophyll a database is freely available through the Australian Ocean Data
      Network portal (https://portal.aodn.org.au/). These data can be used in isolation
      as an index of phytoplankton biomass or in combination with other data to provide
      insight into water quality, ecosystem state, and relationships with other trophic
      levels such as zooplankton or fish.

PMID- 29461518
TI  - De novo design and engineering of non-ribosomal peptide synthetases.
AB  - Peptides derived from non-ribosomal peptide synthetases (NRPSs) represent an
      important class of pharmaceutically relevant drugs. Methods to generate novel non
      ribosomal peptides or to modify peptide natural products in an easy and
      predictable way are therefore of great interest. However, although the overall
      modular structure of NRPSs suggests the possibility of adjusting domain
      specificity and selectivity, only a few examples have been reported and these
      usually show a severe drop in production titre. Here we report a new strategy for
      the modification of NRPSs that uses defined exchange units (XUs) and not modules
      as functional units. XUs are fused at specific positions that connect the
      condensation and adenylation domains and respect the original specificity of the
      downstream module to enable the production of the desired peptides. We also
      present the use of internal condensation domains as an alternative to other
      peptide-chain-releasing domains for the production of cyclic peptides.

PMID- 29461519
TI  - Evaluating differences in the active-site electronics of supported Au
      nanoparticle catalysts using Hammett and DFT studies.
AB  - Supported metal catalysts, which are composed of metal nanoparticles dispersed on
      metal oxides or other high-surface-area materials, are ubiquitous in industrially
      catalysed reactions. Identifying and characterizing the catalytic active sites on
      these materials still remains a substantial challenge, even though it is required
      to guide rational design of practical heterogeneous catalysts. Metal-support
      interactions have an enormous impact on the chemistry of the catalytic active
      site and can determine the optimum support for a reaction; however, few direct
      probes of these interactions are available. Here we show how benzyl alcohol
      oxidation Hammett studies can be used to characterize differences in the
      catalytic activity of Au nanoparticles hosted on various metal-oxide supports. We
      combine reactivity analysis with density functional theory calculations to
      demonstrate that the slope of experimental Hammett plots is affected by electron
      donation from the underlying oxide support to the Au particles.

PMID- 29461520
TI  - Pt/Cu single-atom alloys as coke-resistant catalysts for efficient C-H
      activation.
AB  - The recent availability of shale gas has led to a renewed interest in C-H bond
      activation as the first step towards the synthesis of fuels and fine chemicals.
      Heterogeneous catalysts based on Ni and Pt can perform this chemistry, but
      deactivate easily due to coke formation. Cu-based catalysts are not practical due
      to high C-H activation barriers, but their weaker binding to adsorbates offers
      resilience to coking. Using Pt/Cu single-atom alloys (SAAs), we examine C-H
      activation in a number of systems including methyl groups, methane and butane
      using a combination of simulations, surface science and catalysis studies. We
      find that Pt/Cu SAAs activate C-H bonds more efficiently than Cu, are stable for
      days under realistic operating conditions, and avoid the problem of coking
      typically encountered with Pt. Pt/Cu SAAs therefore offer a new approach to coke
      resistant C-H activation chemistry, with the added economic benefit that the
      precious metal is diluted at the atomic limit.

PMID- 29461521
TI  - Rounding up lutetium.

PMID- 29461522
TI  - Substrate-driven chemotactic assembly in an enzyme cascade.
AB  - Enzymatic catalysis is essential to cell survival. In many instances, enzymes
      that participate in reaction cascades have been shown to assemble into metabolons
      in response to the presence of the substrate for the first enzyme. However, what
      triggers metabolon formation has remained an open question. Through a combination
      of theory and experiments, we show that enzymes in a cascade can assemble via
      chemotaxis. We apply microfluidic and fluorescent spectroscopy techniques to
      study the coordinated movement of the first four enzymes of the glycolysis
      cascade: hexokinase, phosphoglucose isomerase, phosphofructokinase and aldolase.
      We show that each enzyme independently follows its own specific substrate
      gradient, which in turn is produced by the preceding enzymatic reaction.
      Furthermore, we find that the chemotactic assembly of enzymes occurs even under
      cytosolic crowding conditions.

PMID- 29461523
TI  - Evolving artificial metalloenzymes via random mutagenesis.
AB  - Random mutagenesis has the potential to optimize the efficiency and selectivity
      of protein catalysts without requiring detailed knowledge of protein structure;
      however, introducing synthetic metal cofactors complicates the expression and
      screening of enzyme libraries, and activity arising from free cofactor must be
      eliminated. Here we report an efficient platform to create and screen libraries
      of artificial metalloenzymes (ArMs) via random mutagenesis, which we use to
      evolve highly selective dirhodium cyclopropanases. Error-prone PCR and
      combinatorial codon mutagenesis enabled multiplexed analysis of random mutations,
      including at sites distal to the putative ArM active site that are difficult to
      identify using targeted mutagenesis approaches. Variants that exhibited
      significantly improved selectivity for each of the cyclopropane product
      enantiomers were identified, and higher activity than previously reported ArM
      cyclopropanases obtained via targeted mutagenesis was also observed. This
      improved selectivity carried over to other dirhodium-catalysed transformations,
      including N-H, S-H and Si-H insertion, demonstrating that ArMs evolved for one
      reaction can serve as starting points to evolve catalysts for others.

PMID- 29461524
TI  - Asymmetric transfer hydrogenation by synthetic catalysts in cancer cells.
AB  - Catalytic anticancer metallodrugs active at low doses could minimize side
      effects, introduce novel mechanisms of action that combat resistance and widen
      the spectrum of anticancer-drug activity. Here we use highly stable chiral half
      sandwich organometallic Os(II) arene sulfonyl diamine complexes,
      [Os(arene)(TsDPEN)] (TsDPEN, N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine),
      to achieve a highly enantioselective reduction of pyruvate, a key intermediate in
      metabolic pathways. Reduction is shown both in aqueous model systems and in human
      cancer cells, with non-toxic concentrations of sodium formate used as a hydride
      source. The catalytic mechanism generates selectivity towards ovarian cancer
      cells versus non-cancerous fibroblasts (both ovarian and lung), which are
      commonly used as models of healthy proliferating cells. The formate precursor N
      formylmethionine was explored as an alternative to formate in PC3 prostate cancer
      cells, which are known to overexpress a deformylase enzyme. Transfer
      hydrogenation catalysts that generate reductive stress in cancer cells offer a
      new approach to cancer therapy.

PMID- 29461525
TI  - Transferring the entatic-state principle to copper photochemistry.
AB  - The entatic state denotes a distorted coordination geometry of a complex from its
      typical arrangement that generates an improvement to its function. The entatic
      state principle has been observed to apply to copper electron-transfer proteins
      and it results in a lowering of the reorganization energy of the electron
      transfer process. It is thus crucial for a multitude of biochemical processes,
      but its importance to photoactive complexes is unexplored. Here we study a copper
      complex-with a specifically designed constraining ligand geometry-that exhibits
      metal-to-ligand charge-transfer state lifetimes that are very short. The
      guanidine-quinoline ligand used here acts on the bis(chelated) copper(I) centre,
      allowing only small structural changes after photoexcitation that result in very
      fast structural dynamics. The data were collected using a multimethod approach
      that featured time-resolved ultraviolet-visible, infrared and X-ray absorption
      and optical emission spectroscopy. Through supporting density functional
      calculations, we deliver a detailed picture of the structural dynamics in the
      picosecond-to-nanosecond time range.

PMID- 29461526
TI  - Complex supramolecular interfacial tessellation through convergent multi-step
      reaction of a dissymmetric simple organic precursor.
AB  - Interfacial supramolecular self-assembly represents a powerful tool for
      constructing regular and quasicrystalline materials. In particular, complex two
      dimensional molecular tessellations, such as semi-regular Archimedean tilings
      with regular polygons, promise unique properties related to their nontrivial
      structures. However, their formation is challenging, because current methods are
      largely limited to the direct assembly of precursors, that is, where structure
      formation relies on molecular interactions without using chemical
      transformations. Here, we have chosen ethynyl-iodophenanthrene (which features
      dissymmetry in both geometry and reactivity) as a single starting precursor to
      generate the rare semi-regular (3.4.6.4) Archimedean tiling with long-range order
      on an atomically flat substrate through a multi-step reaction. Intriguingly, the
      individual chemical transformations converge to form a symmetric alkynyl-Ag
      alkynyl complex as the new tecton in high yields. Using a combination of
      microscopy and X-ray spectroscopy tools, as well as computational modelling, we
      show that in situ generated catalytic Ag complexes mediate the tecton conversion.

PMID- 29461527
TI  - Nonribosomal biosynthesis of backbone-modified peptides.
AB  - Biosynthetic modification of nonribosomal peptide backbones represents a
      potentially powerful strategy to modulate the structure and properties of an
      important class of therapeutics. Using a high-throughput assay for catalytic
      activity, we show here that an L-Phe-specific module of an archetypal
      nonribosomal peptide synthetase can be reprogrammed to accept and process the
      backbone-modified amino acid (S)-beta-Phe with near-native specificity and
      efficiency. A co-crystal structure with a non-hydrolysable aminoacyl-AMP analogue
      reveals the origins of the 40,000-fold alpha/beta-specificity switch,
      illuminating subtle but precise remodelling of the active site. When the
      engineered catalyst was paired with downstream module(s), (S)-beta-Phe-containing
      peptides were produced at preparative scale in vitro (~1 mmol) and high titres in
      vivo (~100 mg l-1), highlighting the potential of biosynthetic pathway
      engineering for the construction of novel nonribosomal beta-frameworks.

PMID- 29461528
TI  - Engineered modular biomaterial logic gates for environmentally triggered
      therapeutic delivery.
AB  - The successful transport of drug- and cell-based therapeutics to diseased sites
      represents a major barrier in the development of clinical therapies. Targeted
      delivery can be mediated through degradable biomaterial vehicles that utilize
      disease biomarkers to trigger payload release. Here, we report a modular chemical
      framework for imparting hydrogels with precise degradative responsiveness by
      using multiple environmental cues to trigger reactions that operate user
      programmable Boolean logic. By specifying the molecular architecture and
      connectivity of orthogonal stimuli-labile moieties within material cross-linkers,
      we show selective control over gel dissolution and therapeutic delivery. To
      illustrate the versatility of this methodology, we synthesized 17 distinct
      stimuli-responsive materials that collectively yielded all possible YES/OR/AND
      logic outputs from input combinations involving enzyme, reductant and light.
      Using these hydrogels we demonstrate the first sequential and environmentally
      stimulated release of multiple cell lines in well-defined combinations from a
      material. We expect these platforms will find utility in several diverse fields
      including drug delivery, diagnostics and regenerative medicine.

PMID- 29461529
TI  - Biosynthesis: Reprogramming assembly lines.

PMID- 29461530
TI  - Ultrafast dynamics of low-energy electron attachment via a non-valence
      correlation-bound state.
AB  - The primary electron-attachment process in electron-driven chemistry represents
      one of the most fundamental chemical transformations with wide-ranging importance
      in science and technology. However, the mechanistic detail of the seemingly
      simple reaction of an electron and a neutral molecule to form an anion remains
      poorly understood, particularly at very low electron energies. Here, time
      resolved photoelectron imaging was used to probe the electron-attachment process
      to a non-polar molecule using time-resolved methods. An initially populated
      diffuse non-valence state of the anion that is bound by correlation forces
      evolves coherently in ~30 fs into a valence state of the anion. The extreme
      efficiency with which the correlation-bound state serves as a doorway state for
      low-energy electron attachment explains a number of electron-driven processes,
      such as anion formation in the interstellar medium and electron attachment to
      fullerenes.

PMID- 29461531
TI  - Endothermic singlet fission is hindered by excimer formation.
AB  - Singlet fission is a process whereby two triplet excitons can be produced from
      one photon, potentially increasing the efficiency of photovoltaic devices.
      Endothermic singlet fission is desired for a maximum energy-conversion
      efficiency, and such systems have been considered to form an excimer-like state
      with multiexcitonic character prior to the appearance of triplets. However, the
      role of the excimer as an intermediate has, until now, been unclear. Here we
      show, using 5,12-bis((triisopropylsilyl)ethynyl)tetracene in solution as a
      prototypical example, that, rather than acting as an intermediate, the excimer
      serves to trap excited states to the detriment of singlet-fission yield. We
      clearly demonstrate that singlet fission and its conjugate process, triplet
      triplet annihilation, occur at a longer intermolecular distance than an excimer
      intermediate would impute. These results establish that an endothermic singlet
      fission material must be designed to avoid excimer formation, thus allowing
      singlet fission to reach its full potential in enhancing photovoltaic energy
      conversion.

PMID- 29461532
TI  - Uranium electrocatalysis: The secret is in the ring.

PMID- 29461533
TI  - The role of uranium-arene bonding in H2O reduction catalysis.
AB  - The reactivity of uranium compounds towards small molecules typically occurs
      through stoichiometric rather than catalytic processes. Examples of uranium
      catalysts reacting with water are particularly scarce, because stable uranyl
      groups form that preclude the recovery of the uranium compound. Recently,
      however, an arene-anchored, electron-rich uranium complex has been shown to
      facilitate the electrocatalytic formation of H2 from H2O. Here, we present the
      precise role of uranium-arene delta bonding in intermediates of the catalytic
      cycle, as well as details of the atypical two-electron oxidative addition of H2O
      to the trivalent uranium catalyst. Both aspects were explored by synthesizing mid
      and high-valent uranium-oxo intermediates and by performing comparative studies
      with a structurally related complex that cannot engage in delta bonding. The
      redox activity of the arene anchor and a covalent delta-bonding interaction with
      the uranium ion during H2 formation were supported by density functional theory
      analysis. Detailed insight into this catalytic system may inspire the design of
      ligands for new uranium catalysts.

PMID- 29461534
TI  - Correction.
AB  - This corrects the article DOI: 10.1038/nchem.2914.

PMID- 29461535
TI  - Direct observation of the influence of cardiolipin and antibiotics on lipid II
      binding to MurJ.
AB  - Translocation of lipid II across the cytoplasmic membrane is essential in
      peptidoglycan biogenesis. Although most steps are understood, identifying the
      lipid II flippase has yielded conflicting results, and the lipid II binding
      properties of two candidate flippases-MurJ and FtsW-remain largely unknown. Here
      we apply native mass spectrometry to both proteins and characterize lipid II
      binding. We observed lower levels of lipid II binding to FtsW compared to MurJ,
      consistent with MurJ having a higher affinity. Site-directed mutagenesis of MurJ
      suggests that mutations at A29 and D269 attenuate lipid II binding to MurJ,
      whereas chemical modification of A29 eliminates binding. The antibiotic
      ramoplanin dissociates lipid II from MurJ, whereas vancomycin binds to form a
      stable complex with MurJ:lipid II. Furthermore, we reveal cardiolipins associate
      with MurJ but not FtsW, and exogenous cardiolipins reduce lipid II binding to
      MurJ. These observations provide insights into determinants of lipid II binding
      to MurJ and suggest roles for endogenous lipids in regulating substrate binding.

PMID- 29461536
TI  - Oxygen redox chemistry without excess alkali-metal ions in Na2/3[Mg0.28Mn0.72]O2.
AB  - The search for improved energy-storage materials has revealed Li- and Na-rich
      intercalation compounds as promising high-capacity cathodes. They exhibit
      capacities in excess of what would be expected from alkali-ion
      removal/reinsertion and charge compensation by transition-metal (TM) ions. The
      additional capacity is provided through charge compensation by oxygen redox
      chemistry and some oxygen loss. It has been reported previously that oxygen redox
      occurs in O 2p orbitals that interact with alkali ions in the TM and alkali-ion
      layers (that is, oxygen redox occurs in compounds containing Li+-O(2p)-Li+
      interactions). Na2/3[Mg0.28Mn0.72]O2 exhibits an excess capacity and here we show
      that this is caused by oxygen redox, even though Mg2+ resides in the TM layers
      rather than alkali-metal (AM) ions, which demonstrates that excess AM ions are
      not required to activate oxygen redox. We also show that, unlike the alkali-rich
      compounds, Na2/3[Mg0.28Mn0.72]O2 does not lose oxygen. The extraction of alkali
      ions from the alkali and TM layers in the alkali-rich compounds results in
      severely underbonded oxygen, which promotes oxygen loss, whereas Mg2+ remains in
      Na2/3[Mg0.28Mn0.72]O2, which stabilizes oxygen.

PMID- 29461538
TI  - A dataset mapping the potential biophysical effects of vegetation cover change.
AB  - Changing the vegetation cover of the Earth has impacts on the biophysical
      properties of the surface and ultimately on the local climate. Depending on the
      specific type of vegetation change and on the background climate, the resulting
      competing biophysical processes can have a net warming or cooling effect, which
      can further vary both spatially and seasonally. Due to uncertain climate impacts
      and the lack of robust observations, biophysical effects are not yet considered
      in land-based climate policies. Here we present a dataset based on satellite
      remote sensing observations that provides the potential changes i) of the full
      surface energy balance, ii) at global scale, and iii) for multiple vegetation
      transitions, as would now be required for the comprehensive evaluation of land
      based mitigation plans. We anticipate that this dataset will provide valuable
      information to benchmark Earth system models, to assess future scenarios of land
      cover change and to develop the monitoring, reporting and verification guidelines
      required for the implementation of mitigation plans that account for biophysical
      land processes.

PMID- 29461537
TI  - Palladium-catalysed anti-Markovnikov selective oxidative amination.
AB  - In recent years, the synthesis of amines and other nitrogen-containing motifs has
      been a major area of research in organic chemistry because they are widely
      represented in biologically active molecules. Current strategies rely on a
      multistep approach and require one reactant to be activated prior to the carbon
      nitrogen bond formation. This leads to a reaction inefficiency and functional
      group intolerance. As such, a general approach to the synthesis of nitrogen
      containing compounds from readily available and benign starting materials is
      highly desirable. Here we present a palladium-catalysed oxidative amination
      reaction in which the addition of the nitrogen occurs at the less-substituted
      carbon of a double bond, in what is known as anti-Markovnikov selectivity.
      Alkenes are shown to react with imides in the presence of a palladate catalyst to
      generate the terminal imide through trans-aminopalladation. Subsequently, olefin
      isomerization occurs to afford the thermodynamically favoured products. Both the
      scope of the transformation and mechanistic investigations are reported.

PMID- 29461539
TI  - [Improving care for cleft lip and palate patients: uniform and patient-orientated
      outcome measures].
AB  - The quality of care for patients with cleft lip and palate is extremely variable
      across the world. Treatment protocols differ and methods of data registration are
      not uniform. Improving this care by means of comparative research is challenging.
      The best treatment programmes can be identified by uniformly registering patient
      orientated outcomes and comparing the outcomes with those of other treatment
      centres. That knowledge can be used to improve one's own care. An international
      team consisting of specialists and cleft lip and palate patients has developed a
      set of outcome measures that are considered by patients to be most important.
      This team is coordinated by the International Consortium of Health Outcomes
      Measurement (ICHOM). The cleft lip and palate outcome set can be used by all
      centres worldwide in following up on cleft lip and palate patients. In the
      Erasmus Medical Centre in Rotterdam, the 'Zorgmonitor Schisis' (Care Monitor
      Cleft Lip and Palate) has been built, an application in which these outcome
      measures are collected at fixed times. Implementing this set of outcome measures
      in other cleft lip and palate treatment centres and using the outcomes as
      (inter)national benchmarks will result in transparency and the improvement of the
      treatment of cleft lip and palate worldwide.

PMID- 29461540
TI  - [Juvenile idiopathic arthritis].
AB  - Juvenile idiopathic arthritis (JIA) is the most common cause of chronic
      inflammation of the joints in childhood. Currently, JIA is divided into 7
      subtypes, distinguished on the basis of the symptoms present in the first six
      months of the illness. Pharmacological treatment is different for every subtype.
      With all forms of JIA, dental problems can occur. These can include an increasing
      incidence of dental caries, stomatitis with the use of methotrexate, oral
      candidiasis with the use of immunosuppressive medication and temporal mandibular
      joint (TMJ) arthritis. The detection of TMJ arthritis seems to be especially
      difficult in daily practice. Dentists could play a role in identifying the TMJ
      complication in children with JIA.

PMID- 29461541
TI  - [The use of scientific journals and professional periodicals by Dutch dental
      students].
AB  - In the present study, the extent to which dental students in Amsterdam, Groningen
      and Nijmegen consult scientific journals and professional periodicals was
      explored by means of a digital questionnaire. 333 dental students (20% response
      rate) participated in this study, 69% of whom had experience in conducting
      scientific research. 65% of the students had a subscription to a dental journal.
      Of the Dutch-language dental journals, the 'Nederlands Tijdschrift voor
      Tandheelkunde' [Netherlands Journal for Dentistry] and the 'Nederlands
      Tandartsenblad' [Dutch Dentists' Journal] are frequently consulted journals.
      International publications are consulted especially by masters students, although
      less frequently than Dutch dental journals. The study revealed that 77% of the
      students consider it important that attention is paid to the development of
      scientific skills early in the dental curriculum in order to adequately prepare
      students to select and interpret publications.

PMID- 29461542
TI  - [A study to determine possible success variables in the treatment of gag reflex
      patients].
AB  - A disproportionately sensitive gag reflex can hamper adequate dental treatment.
      Because an evidence-based treatment for this condition is lacking at this moment,
      a study of patients and success variables for the treatment was carried out. The
      study was based on the clinical records of and interviews with 40 people who had
      been treated in a Centre for Special Dental Care (CBT) because of extreme gag
      problems two years earlier. It was found that the gag complaints of half of the
      respondents had disappeared or become manageable, while those of the other half
      had not changed. It did not matter which intervention had been adopted. In order
      to determine how patients can best be treated and which patients can best be
      treated, research among larger patient samples is needed.

PMID- 29461543
TI  - [External cervical root resorption].
AB  - External cervical root resorption begins at the root surface as result of
      odontoclastic activity in the cervical area and is progressive in character. The
      pulp is only affected at a later stage of the process. The aetiology and
      pathogenesis of external cervical root resorption is not fully understood.
      Possible predisposing factors are, among others, orthodontic treatment, trauma,
      internal bleaching, damaged cemento-enamel junction, bruxism and hypoxia. A 'pink
      spot' often is the first clinical sign and a two-dimensional radiograph usually
      presents an amorphous radiolucency with undefined borders. Cone-beam computed
      tomography is an emerging technique aiding the diagnosis of and prognosis and
      treatment plans for external root resorption. An external or internal treatment
      approach can be chosen, depending on the size of the defect.

PMID- 29461544
TI  - [A PhD completed. Bilateral sagittal split osteotomy: risk factors for
      complications and predictability of the splitter-separator technique].
AB  - Bilateral sagittal split osteotomy (BSSO) is a surgical technique to correct
      hypoplasia, hyperplasia or asymmetry of the mandible. The risk of complications
      associated with BSSO with splitter and separators, the so-called splitter
      separator technique, and the predictability of this technique were analysed. The
      average incidence of complications associated with classic BSSO techniques was
      determined by a review of the literature. With classic techniques, a bad split
      occurred in 2.3% of the operated sides, removal of osteosynthesis material on
      account of complaints in 11.2% of patients, and permanent neurosensory
      disturbances in the area of the mental nerve in 33.9% of patients. The incidence
      of complications for BSSO with splitter and separators is a bad split in 2.0% of
      the operated sides, necessary removal of osteosynthesis material in 5.6% of
      patients, and permanent neurosensory disturbances of the lower lip in 9.9% of
      patients. Removal of the third molars during BSSO may result in an increased
      chance of bad split but does not increase the risk of other complications. In
      conclusion, BSSO with splitter and separators is a reliable technique, with a
      remarkably low incidence of permanent neurosensory disturbances of the lower lip.

PMID- 29461545
TI  - Temporal trends of halogenated flame retardants in the atmosphere of the Canadian
      Great Lakes Basin (2005-2014).
AB  - Organic pollutants have been monitored in the atmosphere of the Great Lake Basin
      (GLB) since the 1990s in support of the Canada-US Great Lakes Water Quality
      Agreement and to determine the effectiveness of source reduction measures and
      factors influencing air concentrations. Air samples were collected between 2005
      and 2014 at three sites with different geographical characteristics (Burnt
      Island, Egbert and Point Petre) in the Canadian GLB using high-volume air
      samplers and the air samples were analyzed for polybrominated diphenyl ethers
      (PBDEs) and several other non-PBDE halogenated flame retardants (HFRs). Spatial
      and temporal trends of total concentrations of HFRs were examined. BDE-47, BDE
      99, and BDE-209 were the dominant PBDE congeners found at the three sites. For
      the non-PBDE HFRs, allyl 2,4,6-tribromophenyl ether (TBP-AE), hexabromobenzene
      (HBBz), pentabromotoluene (PBT), anti-dechlorane plus (anti-DDC-CO) and syn
      dechlorane plus (syn-DDC-CO) were frequently detected. High atmospheric
      concentrations of PBDEs were found at the Egbert site with a larger population,
      while lower levels of PBDEs were detected at Point Petre, which is close to urban
      centers where control measures are in place. The strong temperature dependence of
      air concentrations indicates that volatilization from local sources influences
      atmospheric concentrations of BDE-28 and BDE-47 at Point Petre and Burnt Island,
      while long-range atmospheric transport (LRAT) was important for BDE-99. However,
      a weaker correlation was observed between air concentrations and ambient
      temperature for non-PBDE HFRs such as TBP-AE and HBBz. Atmospheric PBDE
      concentrations are decreasing slowly, with half-lives in the range of 2-16 years.
      Faster declining trends of PBDEs were observed at Point Petre rather than at
      Burnt Island. As Point Petre is closer to urban centers, faster declining trends
      may reflect the phase out of technical BDE mixtures in urban centers while LRAT
      influences the air concentrations at Burnt Island. The levels of syn-DDC-CO and
      anti-DDC-CO are decreasing at Point Petre and the levels of other non-PBDE HFRs
      such as TBP-AE, PBT and HBBz are increasing. Long-term declining trends of PBDEs
      suggest that regulatory efforts to reduce emissions to the GLB environment have
      been effective but that continuous measurements are required to gain a better
      understanding of the trends of emerging chemicals in the atmosphere of the GLB.

PMID- 29461546
TI  - Assembly and activation of supported cobalt nanocrystal catalysts for the Fischer
      Tropsch synthesis.
AB  - The effect of oxidative treatments on the depostion of cobalt nanocrystals (Co
      NC) onto a support and subsequent ligand removal was investigated. Deposition of
      epsilon-cobalt NC led to extensive clustering of NC and low Fischer-Tropsch
      synthesis activity. Low-temperature oxidation of epsilon-cobalt NC resulted in a
      very uniform CoO-NC distribution and high activity whereas high-temperature
      oxidation to Co3O4 led to less uniform NC distributions and lower activity.

PMID- 29461547
TI  - Polydiacetylene liposomes with phenylboronic acid tags: a fluorescence turn-on
      sensor for sialic acid detection and cell-surface glycan imaging.
AB  - Sialic acid (SA) located at the terminal end of glycans on cell membranes has
      been shown to play an important yet distinctive role in various biological and
      pathological processes. Effective methods for the facile, sensitive and in situ
      analysis of SA on living cell surfaces are of great significance in terms of
      clinical diagnostics and therapeutics. Here, a new polydiacetylene (PDA) liposome
      based sensor system bearing phenylboronic acid (PBA) and 1,8-naphthalimide
      derived fluorophore moieties was developed as a fluorescence turn-on sensor for
      the detection of free SA in aqueous solution and the in situ imaging of SA
      terminated glycans on living cell surfaces. In the sensor system, three
      diacetylene monomers, PCDA-pBA, PCDA-Nap and PCDA-EA, were designed and
      synthesized to construct the composite PDA liposome sensor. The monomer PCDA-pBA
      modified with PBA molecules was employed as a receptor for SA recognition, while
      the monomer PCDA-Nap containing a 1,8-naphthalimide derivative fluorophore was
      used for fluorescence signaling. When the composite PDA liposomes were formed,
      the energy transfer between the fluorophore and the conjugated backbone could
      directly quench the fluorescence of the fluorophore. In the presence of
      additional SA or SA abundant cells, the strong binding of SA with PBA moieties
      disturbed the pendent side chain conformation, resulting in the fluorescence
      restoration of the fluorophore. The proposed methods realized the fluorescence
      turn-on detection of free SA in aqueous solution and the in situ imaging of SA on
      living MCF-7 cell surfaces. This work provides a new potential tool for simple
      and selective analysis of SA on living cell membranes.

PMID- 29461548
TI  - Direct measurement of surface charge distribution in phase separating supported
      lipid bilayers.
AB  - The local surface charge density of the cell membrane influences regulation and
      localization of membrane proteins. The local surface charge density could, until
      recently, not be measured directly under physiological conditions, and it was
      largely a hypothetical yet very important parameter. Here we use unsaturated
      lipids of a distinct charge (DOTAP, DOPC, and DOPG) and a neutral fully saturated
      lipid (DPPC) to create model membranes with phase separating domains of a defined
      charge. We then apply quantitative surface charge microscopy (QSCM) to
      investigate the local surface charge density; this is a technique based on a
      scanning ion conductance microscope (SICM) capable of measuring surface charge
      density with nanoscale lateral resolution. We are able to clearly distinguish
      lipid domains from charge and topography in all three model membranes. The
      measured surface charge densities furthermore reveal that disordered domains
      formed by charged lipids are in fact not only impure, but also incorporate
      uncharged saturated lipids. We estimate that at least 30% of disordered domains
      in DOPG : DPPC and DOTAP : DPPC will be DPPC. These ratios could present a limit
      for the formation of charged domains in lipid membranes.

PMID- 29461550
TI  - Pd(ii)-Catalyzed asymmetric 1,6-conjugate addition of arylboronic acids to
      Meldrum's acid-derived dienes.
AB  - A Pd(ii)-catalyzed asymmetric 1,6-addition of arylboronic acids to Meldrum's acid
      derived dienes was developed. A new substituted In-Pyrox ligand was designed to
      enable this reaction with high enantioselectivity via a remote steric effect. A
      series of Meldrum's acid-derived dienes and arylboronic acids were tolerable to
      the reaction conditions, giving the desired adducts in moderate to high yields
      with good enantioselectivities (up to 96% ee). This reaction provides the first
      method of Pd(ii)-catalyzed asymmetric 1,6-conjugate addition of arylboron.

PMID- 29461549
TI  - Force determination in lateral magnetic tweezers combined with TIRF microscopy.
AB  - Combining single-molecule techniques with fluorescence microscopy has attracted
      much interest because it allows the correlation of mechanical measurements with
      directly visualized DNA : protein interactions. In particular, its combination
      with total internal reflection fluorescence microscopy (TIRF) is advantageous
      because of the high signal-to-noise ratio this technique achieves. This, however,
      requires stretching long DNA molecules across the surface of a flow cell to
      maximize polymer exposure to the excitation light. In this work, we develop a
      module to laterally stretch DNA molecules at a constant force, which can be
      easily implemented in regular or combined magnetic tweezers (MT)-TIRF setups. The
      pulling module is further characterized in standard flow cells of different
      thicknesses and glass capillaries, using two types of micrometer size
      superparamagnetic beads, long DNA molecules, and a home-built device to rotate
      capillaries with mrad precision. The force range achieved by the magnetic pulling
      module was between 0.1 and 30 pN. A formalism for estimating forces in flow
      stretched tethered beads is also proposed, and the results compared with those of
      lateral MT, demonstrating that lateral MT achieve higher forces with lower
      dispersion. Finally, we show the compatibility with TIRF microscopy and the
      parallelization of measurements by characterizing DNA binding by the centromere
      binding protein ParB from Bacillus subtilis. Simultaneous MT pulling and
      fluorescence imaging demonstrate the non-specific binding of BsParB on DNA under
      conditions restrictive to condensation.

PMID- 29461551
TI  - Aggregation of polyethylene glycol polymers suppresses receptor-mediated
      endocytosis of PEGylated liposomes.
AB  - The PEGylated liposome, composed of an aqueous core and a fluid state lipid
      bilayer shell, is one of the few Food and Drug Administration (FDA) approved drug
      delivery platforms. To prevent the absorption of serum proteins, the surface of a
      liposome is decorated by hydrophilic and bio-compatible polyethylene glycol (PEG)
      polymers, which can significantly extend the blood circulation time of liposomes.
      In this work, with the help of dissipative particle dynamics (DPD) simulations,
      we explore how the tethered PEG polymers will affect the membrane wrapping
      process of PEGylated liposomes during endocytosis. Specifically, we compare the
      membrane wrapping process of a PEGylated rigid nanoparticle (NP) with a PEGylated
      liposome under identical conditions. Due to the mobility of grafted PEG polymers
      on the liposome's surface, the complete wrapping of a PEGylated liposome can be
      dramatically delayed and blocked, in comparison with a PEGylated rigid NP. For
      the first time, we observe the aggregation of PEG polymers in the contact region
      between a PEGylated liposome and the membrane, which in turn leads to a ligand
      free region on the surface of the liposome during endocytosis. Subsequently, the
      partially wrapped PEGylated liposome can be bounced back to a less wrapped state.
      Through free energy analysis, we find that the aggregation of PEG polymers during
      the membrane wrapping process of a PEGylated liposome introduces a dramatic free
      energy penalty of about ~800kBT, which is almost twice that of a PEGylated rigid
      NP. Here kB and T are the Boltzmann constant and temperature, respectively. Such
      a large energy barrier and the existence of a ligand-free region on the surface
      of PEGlylated liposomes prevent their membrane wrapping, thereby reducing the
      chance of internalization by tumor cells. Therefore, our DPD simulation results
      provide a possible explanation for the inefficient cellular uptake of PEGylated
      liposomes. In addition, we suggest that by increasing the repulsive interactions
      between grafted PEG polymers it might be possible to limit their aggregation, and
      in turn, facilitate the internalization of PEGylated liposomes. The current study
      provides fundamental insights into the endocytosis of PEGylated liposomes, which
      could help to design this platform with high efficacy for drug delivery.

PMID- 29461552
TI  - KI-catalyzed C-S bond formation via an oxidation relay strategy: efficient access
      to various alpha-thio-beta-dicarbonyl compounds.
AB  - An efficient and practical methodology to obtain alpha-thio-beta-dicarbonyl
      compounds was presented under alkaline conditions via potassium iodide (KI)
      catalysis; various symmetrical/unsymmetrical 1,3-dicarbonyl compounds were
      obtained under an aerobic atmosphere in moderate to excellent yields, with good
      functional group tolerance. Notably, a widely used anti-inflammatory drug
      butazodine could be modified with our protocol, even on a gram scale.

PMID- 29461553
TI  - Current state of bioanalytical chromatography in clinical analysis.
AB  - Chromatographic methods have become popular in clinical analysis in both routine
      and research laboratories. The purpose of this review article is to provide an
      overview of the current state of chromatographic methods, i.e., high-performance
      liquid chromatography (HPLC), gas chromatography (GC), and supercritical fluid
      chromatography (SFC), in clinical analysis. The aspects related to method
      sensitivity, selectivity, analysis time, and throughput have been discussed in
      detail. Adequate solutions to improve these features have also been presented.
      HPLC is the most widely used method among the chromatographic methods, whereas GC
      is dedicated to several specific applications, and SFC is used only marginally
      certainly due to its only recent comeback to the analytical scene. Based on the
      literature search, the application fields in clinical analysis are divided into
      the following groups: drugs, hormones, drugs of abuse, metabolomics, lipidomics,
      volatile organic compounds, biomarkers and endogenous compounds, proteomics,
      multi-analyte approches, and others. The important features of these applications
      have been emphasized.

PMID- 29461554
TI  - A diarsagermylene and a diarsastannylene stabilised by areneGe/Sn interactions.
AB  - The synthesis and structures of two new diarsatetrylenes {(Dipp)2As}2E are
      presented [E = Ge, Sn; Dipp = 2,6-diisopropylphenyl]. The high barrier to
      planarisation of As prevents stabilisation by As-E pi-interactions; however,
      areneGe/Sn interactions stabilise these compounds by up to 181.4 kJ mol-1. This
      represents a new stabilisation mode for this class of compounds.

PMID- 29461555
TI  - Construction of bridged cyclic N,O-ketal spirooxindoles through a Michael
      addition/N,O-ketalization sequence.
AB  - The first highly diastereoselective TfOH-catalyzed Michael addition/N,O
      ketalization sequence of 3-aminooxindoles and ortho-hydroxychalcones was
      achieved, delivering a wide range of bridged cyclic N,O-ketal spirooxindoles with
      complex and strained structures in 41-97% yields. Moreover, a gram-scale
      experiment and some chemical conversions were conducted to further demonstrate
      the synthetic value.

PMID- 29461556
TI  - Nitrogen atom transfer mediated by a new PN3P-pincer nickel core via a putative
      nitrido nickel intermediate.
AB  - A 2nd generation PN3P-pincer azido nickel complex (PN3P)Ni(N3) reacts with
      isocyanides to afford monosubstituted carbodiimides under irradiation, presumably
      via a transient nitrido intermediate. The resulting species can further generate
      unsymmetrical carboddimides and the PN3P nickel halide complex, accomplishing a
      synthetic cycle for a complete nitrogen atom transfer reaction.

PMID- 29461557
TI  - Superwetting copper meshes based on self-organized robust CuO nanorods: efficient
      water purification for in situ oil removal and visible light photodegradation.
AB  - Water pollution has become a prominent environmental problem and insoluble oils
      and soluble dyes are the primary pollution sources. Herein, a facile and
      environment friendly method is proposed to fabricate robust CuO nanorod-covered
      meshes for dual-functional water purification. The as-prepared meshes can
      efficiently eliminate oils in wastewater and in situ photodegrade soluble organic
      dyes under visible light irradiation. Such a functional mesh is free-standing and
      recyclable, indicating the outstanding practicability of water sewage disposal.
      In consideration of the superiority of low-cost materials, simple method, visible
      light response, ultrahigh purification efficiency and reusability, the as
      prepared meshes are promising in the field of multi-functional water
      purification.

PMID- 29461558
TI  - Bulk and surface properties of metal carbides: implications for catalysis.
AB  - We present a comprehensive study of the bulk and surface properties of transition
      metal carbides with rock salt structures and discuss their formation energies and
      electronic structures. The bonding character of the materials is shown to be
      dependent on the periodic position of the transition metal as well as the surface
      termination, which in turn tunes the densities of states and electronic surface
      properties. Specific focus is given to the possible catalytic implications of the
      surface properties on CO2 hydrogenation.

PMID- 29461559
TI  - Role of topological scale in the differential fouling of Pseudomonas aeruginosa
      and Staphylococcus aureus bacterial cells on wrinkled gold-coated polystyrene
      surfaces.
AB  - Wrinkled patterns, which possess an extensive surface area over a limited planar
      space, can provide surface features ranging across the nano- and microscale that
      have become an engineering material with the flexibility to be tuneable for a
      number of technologies. Here, we investigate the surface parameters that
      influence the attachment response of two model bacteria (P. aeruginosa and S.
      aureus) to wrinkled gold-coated polystyrene surfaces having topologies at the
      nano- and microscale. Together with flat gold films as the controls, surface
      feature heights spanned 2 orders of magnitude (15 nm, 200 nm, and 1 micron). The
      surface wrinkle topology was shown through confocal laser scanning microscopic,
      atomic force microscopic and scanning electron microscopic image analyses to
      consist of air-water interfacial areas unavailable for bacterial attachment,
      which were also shown to be stable by time-lapsed contact angle measurements.
      Imposition of the nanoscale wrinkles reduced P. aeruginosa attachment to 57% and
      S. aureus attachment to 20% of their flat equivalent surfaces whereas wrinkles at
      the microscale further reduced these attachments to 7.5% and 14.5%, respectively.
      The density of attachments indicated an inherent species specific selectivity
      that changed with feature dimension, attributable to the scale of the air-water
      interfaces in contact with the bacterial cell. Parameters influencing static
      bacterial attachment were the total projected surface areas minus the air-water
      interface areas and the scale of these respective air-water interfaces (area
      distribution) with respect to the cell morphology. The range of these controlling
      parameters may provide new design principles for the evolving suite of physical
      anti-biofouling materials not reliant on biocidal agents under development.

PMID- 29461560
TI  - One-pot preparation of polymer microspheres with different porous structures to
      sequentially release bio-molecules for cutaneous regeneration.
AB  - Herein, we reveal a double emulsion method combining the sol-gel method to
      prepare poly(lactic-co-glycolic acid) microspheres with different porous
      structures for sequential release of two types of biomolecules. By controlling
      the ripening time of the emulsion, multiple interconnected chambers could be
      easily chosen to be either embedded in microspheres or opened to the surface.
      These two types of microspheres exhibited different kinetics for the release of
      both small molecules and proteins, where the release from microspheres with open
      pores (5 day over 90%) was much faster than the release from microspheres with
      embedded pores (25 day over 90%). After loading with interleukin-4 (IL-4) and
      melatonin, these microspheres were further encapsulated in a sodium alginate
      hydrogel to form a patch for cutaneous regeneration. The prepared patch was able
      to recruit alternatively activated (M2) macrophages in the early stage (fast
      release of IL-4) and promote the growth of blood vessels in the long term (slow
      release of melatonin), resulting in significantly enhanced cutaneous
      regeneration. These results also demonstrate the potential of this novel delivery
      system to deliver multiple therapeutics and achieve synergistic effects.

PMID- 29461561
TI  - Metastable morphological states of catalytic nanoparticles.
AB  - During the catalytic synthesis of graphene, nanotubes, fibers, and other
      nanostructures, many intriguing phenomena occur, such as phase separation,
      precipitation, and analogs of capillary action. Here, we demonstrate, using in
      situ, real-time transmission electron microscope imaging and modeling, that the
      catalytic nanoparticles display functional, metastable states, reminiscent of
      some protein ensembles in vivo. As a carbon nanostructure grows, the nanoparticle
      elongates due to an energetically favorable metal-carbon interaction that
      overrides the surface energy increase of the metal. The formation of subsequent
      nested tubes, however, drives up the particle's free energy, but the particle
      remains trapped until an accessible free energy surface allows it to exit the
      tube. During this time, the nanoparticle continues to catalyze tube growth
      internally to the nested structure. This universal nonequilibrium thermodynamic
      cycle of elongation and retraction is heavily influenced by tapering of the
      structure, which, ultimately, determines the final product and catalyst lifetime.
      Our results provide a unifying framework to interpret similar phenomena for other
      catalytic reactions, such as during CO oxidation and boron nitride tube growth,
      and suggest routes to the practical optimization of such processes.

PMID- 29461562
TI  - In situ TEM observation of rebonding on fractured silicon carbide.
AB  - Silicon carbide (SiC) is widely used in harsh environments and under extreme
      conditions, including at high-power, high-temperature, high-current, high-voltage
      and high-frequency. The rebonding and self-matching of stack faults (SFs) is
      highly desirable to avoid catastrophic failure for SiC devices, especially for
      specific applications in the aerospace and nuclear power industries. In this
      study, a novel approach was developed using an eyebrow hair to pick up and
      transfer nanowires (NWs), in order to obtain in situ transmission electron
      microscope (TEM) images of the rebonding and self-matching of SFs at atomic
      resolution. During rebonding and healing, the electron beam was shut off.
      Rebonding on the fractured surfaces of monocrystalline and amorphous SiC NWs was
      observed by in situ TEM at room temperature. The fracture strength was 1.7 GPa
      after crack-healing, restoring 12.9% of that of a single crystal NW. Partial
      recrystallization along the <111> orientation and the self-matching of SFs are
      responsible for the rebonding of the monocrystalline NW. In comparison, the
      fracture strengths were 6.7 and 5.5 GPa for the first and second rebonding,
      respectively recovering 67% and 55% of that of an amorphous NW. Atomic diffusion
      contributed enormously to the rebonding on fractured surfaces of an amorphous NW,
      resulting in a healed surface consisting of an amorphous phase and crystallites.
      This rebonding function provides new insight into the fabrication of high
      performance SiC devices for the aerospace, optoelectronic and semiconductor
      industries.

PMID- 29461563
TI  - External skeletal robusticity of children and adolescents - European references
      from birth to adulthood and international comparisons.
AB  - ABSTRACT: Background: In our modern world, the way of life in nutritional and
      activity behaviour has changed. As a consequence, parallel trends of an epidemic
      of overweight and a decline in external skeletal robusticity are observed in
      children and adolescents. Aim: We aim to develop reference centiles for external
      skeletal robusticity of European girls and boys aged 0 to 18 years using the
      Frame Index as an indicator and identify population specific age-related
      patterns. Methods: We analysed cross-sectional & longitudinal data on body height
      and elbow breadth of boys and girls from Europe (0-18 years, n = 41.679), India
      (7-18 years, n = 3.297) and South Africa (3-18 years, n = 4.346). As an indicator
      of external skeletal robusticity Frame Index after Frisancho (1990) was used. We
      developed centiles for boys and girls using the LMS-method and its extension.
      Results: Boys have greater external skeletal robusticity than girls. Whereas in
      girls Frame Index decreases continuously during growth, an increase of Frame
      Index from 12 to 16 years in European boys can be observed. Indian and South
      African boys are almost similar in Frame Index to European boys. In girls, the
      pattern is slightly different. Whereas South African girls are similar to
      European girls, Indian girls show a lesser external skeletal robusticity.
      Conclusion: Accurate references for external skeletal robusticity are needed to
      evaluate if skeletal development is adequate per age. They should be used to
      monitor effects of changes in way of life and physical activity levels in
      children and adolescents to avoid negative health outcomes like osteoporosis and
      arthrosis.

PMID- 29461564
TI  - Growth prediction of small for gestational age infants within the first weeks
      after birth.
AB  - ABSTRACT: Being born small for gestational age (SGA) in length is a sign of
      growth failure due to malnutrition in pregnancy or other serious disorders. In
      previous publications it was shown that SGA born neonates may experience a
      compensatory growth spurt (catch-up growth) in infancy and childhood (Olbertz et
      al. in press). The timing of this growth spurt, however, was not well described.
      We analyzed longitudinal data of 5,138 SGA infants and children, collected by
      licensed physicians in Germany and centrally stored in the Database Management
      System of CrescNet at the University of Leipzig. We confirm that SGA born infants
      undergo a catch-up in height SDS after birth and up to 2 years of life. 2,712 SGA
      newborns out of 2,846 showed catch-up in length SDS. The catch-up occurred
      already during the 4th to 16th postnatal weeks. We analyzed infants who did not
      show a catch-up within this time period, or even had a loss in height SDS. These
      infants have a significant lower height SDS throughout the first 5 years after
      birth and especially in the timeframe of 60th to 64th month after birth (-1.33
      mean height SDS in catch-up group, -2.49 in non-catch-up group, p-value < 0.001,
      CI = [0.827, 1.483]). Even though the medical reasons for the lack of catch-up
      growth in young SGA infants may not be known, absence of this catch-up within the
      4th to 16th postnatal week can be used to early identify SGA infants with high
      risk of growth failure within the following 5 years.

PMID- 29461565
TI  - Editorial Perceiving stunting - Student research and the "Lieschen Muller effect"
      in nutrition science.

PMID- 29461566
TI  - ?
AB  - Do novel therapies in type 2 diabetes have protective effects on cardiovascular
      and renal complications? A number of new antidiabetic drug classes have been
      introduced on the market in the last decade. Regulatory authorities have required
      that their safety in type 2 diabetes populations with high cardiovascular risk
      must be assessed. Consequently, a large number of outcome studies have been
      initiated, several of which have been published in recent years. Overall, this
      has so far shown that long-acting insulin analogues, DPP4-inhibitors, GLP1
      receptor agonists and SGLT2-inhibitors are safe. In addition, a few select agents
      within the latter two classes have been shown to be superior to placebo with
      respect to cardiovascular as well as renal outcomes. This review summarizes these
      recent trials and discusses how the results can be interpreted. It is important
      to emphasize that the subjects included in these studies had/have high risk for
      or manifest cardiovascular disease. Therefore, the results cannot be extrapolated
      to all individuals with type 2 diabetes.

PMID- 29461567
TI  - Diagnosis and treatment goals in diabetes type
AB  - The article presents diagnostic criteria for diabetes and treatment goals for
      diabetes type 2.

PMID- 29461568
TI  - ?

PMID- 29461569
TI  - ?

PMID- 29461570
TI  - ?

PMID- 29461572
TI  - ?

PMID- 29461571
TI  - ?

PMID- 29461573
TI  - ?

PMID- 29461574
TI  - ?

PMID- 29461575
TI  - ?

PMID- 29461576
TI  - ?

PMID- 29461577
TI  - ?

PMID- 29461578
TI  - ?

PMID- 29461579
TI  - ?
AB  - Syphilis - an old imitator is back on the stage Syphilis is one of the oldest
      sexually transmitted infections and caused by the spirochete Treponema pallidum.
      The incubation time is 10-90 days and patients are contagious for approximately
      one year. In Sweden all blood donors and pregnant women are screened. By law,
      individuals with early syphilis (primary and secondary stages) are reported and
      contact tracing is performed. The syphilis incidence is increasing in Europe, USA
      and many other countries. The main drivers are men having sex with men.
      Diagnosing syphilis can be challenging because the non-tender, often genital
      ulcer of primary syphilis can go unnoticed.  Symptoms during secondary syphilis
      can be flu-like such as fever, lymphadenopathy and headache; an unspecific skin
      rash can appear. Serologic tests are usually positive 1-2 weeks after infection.
      Treatment of choice is benzathinpenicilllin 2.4 million units intramuscularly.
      Four case reports illustrate the diverse scenario of syphilis infection.

PMID- 29461580
TI  - Ethnic and cultural aspects of type 2 diabetes
AB  - Political instability the last decades has forced millions of people to migrate
      from their homelands. In Sweden today, 1.6 million are born abroad, of which the
      largest immigrant groups originate from the Middle East. Immigrants from these
      areas represent high risk populations for type 2 diabetes with prevalence of type
      2 diabetes twice as high compared to the native Swedish population. The
      mechanisms behind this increased diabetes risk are not fully unraveled but are
      likely connected to lifestyle, socioeconomic situation, genetics and epigenetics.
      A large proportion still free from diabetes are likely to develop diabetes within
      the coming decade. To prevent this epidemic, increased awareness of risk factors,
      lifestyle habits, potential barriers and of success factors for lifestyle change
      in immigrant populations is important.  Examples of such preventive actions are
      culturally adapted lifestyle interventions addressing cultural barriers and
      behavioral change, which are described in this article.

PMID- 29461581
TI  - ?

PMID- 29461582
TI  - Evaluation of genotyping methods and costs for IL1alpha polymorphisms in Platelet
      Rich-Plasma (PRP); viewpoint for therapy on the diabetic foot ulcers.

PMID- 29461583
TI  - Mediation of inflammation, obesity and fatty liver disease by advanced glycation
      endoproducts.

PMID- 29461584
TI  - Correlation of CT indicators of NSCLC and pathological features and the
      expression level of p53 and c-myc. Positive example of the right way for
      translational diagnostics.

PMID- 29461585
TI  - MicroRNA-125b promotes the regeneration and repair of spinal cord injury through
      regulation of JAK/STAT pathway.
AB  - OBJECTIVE: Spinal cord injury (SCI) is a severe trauma to the central nervous
      system. Long non-coding RNAs have been reported to play essential roles in spinal
      cord injury. This study mainly explored the role of micro-125 in the regulation
      of spinal cord injury by regulating STAT3. MATERIALS AND METHODS: The stable
      mouse model of cervical spinal cord contusion was established by Infinite Horizon
      spinal cord striker, and the model mice' motor function was analyzed.
      Bioinformatics databases were used to screen the target mRNAs of micro-125b. qRT
      PCR was performed to detect the expression of micro-125b and its target genes in
      injury area of mice' spinal cord. Western Blot and ELISA were introduced to
      detect the expression of inflammation and apoptosis-related proteins in each
      group. The recovery status of spinal cord after SCI was assessed by motor
      function scores and axon counts of mice in each group. RESULTS: Micro-125b
      appeared to be significantly down-regulated over-time after SCI. JAK1 and STAT1,
      two important neuregulin proteins, were predicted to be the target genes of micro
      125b, and overexpression of micro-125b induced the decrease of phosphorylated
      JAK1 and STAT1. Enhanced micro-125b expression also allowed axons from the injury
      area of spinal cord to extend into the outer periphery of the damaged area, thus
      improving the motor function of the injured rats. Besides, overexpression of
      micro-125b demonstrated significant neuronal protective effects by reducing
      apoptosis and inflammatory responses in neurons. CONCLUSIONS: Our data revealed
      that micro-125b was down-regulated in injured spinal cord, and overexpression of
      micro-125b promoted the repair and regeneration following spinal cord injury
      through the regulation of the JAK/STAT pathway.

PMID- 29461586
TI  - Diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) values
      for detection of malignant vertebral bone marrow lesions.
AB  - Malignant spinal bone marrow disorders are one of the major causes of significant
      morbidity and reduction in quality of life in oncological patients. Thus, the
      characterization of these conditions is of crucial importance in the management
      of these patients. Magnetic resonance (MR) imaging plays a vital role in
      differentiation between benign and malignant spinal bone marrow disorders.
      However, morphological imaging features, based on T1 and T2 relaxation
      properties, might fail in differentiating between these conditions because signal
      characteristics may overlap. Quantitative MR imaging based on diffusion weighted
      imaging (DWI) and apparent diffusion coefficient (ADC) values has been proved to
      help in defining the nature of the lesion. The aims of this paper were: to review
      basic principles of DWI technique and ADC maps, to describe DWI and ADC maps
      appearances of normal vertebral bone marrow briefly, to discuss the DWI and ADC
      maps characteristics in vertebral malignant lesions, to provide indications for
      differential diagnosis between malignant and benign lesions.

PMID- 29461587
TI  - Primary neoplasms of the small bowel at CT: a pictorial essay for the clinician.
AB  - OBJECTIVE: Primary small intestinal neoplasms are uncommon tumors that are often
      small and difficult to identify. The aim of this paper is to describe CT
      technique and features in detecting and characterizing the tumors of the small
      bowel. MATERIALS AND METHODS: This paper focuses on radiological characteristics
      of benign and malignant primary neoplasms of the small bowel at CT, with special
      reference to multidetector-CT techniques, type and modality of administration of
      contrast agents (by oral route or CT-enterography and by nasojejunal tube or CT
      enteroclysis). This paper will also provide pictures and description of CT
      findings of benign and malignant primary neoplasms using examples of CT
      enterography and CT-enteroclysis. RESULTS: Among CT modalities, CT-enterography
      has the advantage of defining the real extension of wall lesions, possible
      transmural extension, the degree of mesenteric involvement and remote metastasis.
      Other useful modalities for the diagnosis of such lesions like capsule endoscopy
      and enteroscopy, provide important information but limited to mucosal changes
      with lower accuracy on extension and bowel wall involvement or submucosal
      lesions. CONCLUSIONS: Multidetector-CT, performed after distension of the small
      bowel with oral contrast material and intravenous injection of iodinated contrast
      material, is a useful method for the diagnosis and staging of small bowel
      neoplasms.

PMID- 29461588
TI  - SPOP suppresses osteosarcoma invasion via PI3K/AKT/NF-kappaB signaling pathway.
AB  - OBJECTIVE:   Speckle-type POZ protein (SPOP), is an E3 ubiquitin ligase adaptor
      that is frequently mutated in prostate and endometrial cancers. SPOP has been
      shown to be responsible for oncogene SRC-3 ubiquitination and proteolysis in
      prostate cancers.  However, whether SPOP plays a role in osteosarcoma (OS) is
      unknown. In this study, we investigated the inhibitory effect of SPOP on invasion
      and migration of OS cells. PATIENTS AND METHODS: Real-time PCR and Western blot
      were used to detect the expression of SPOP in human OS samples and cell lines.
      Short hairpin RNA (shRNA) was used to silencing the expression of SPOP. Small
      scale Real-time PCR screen was used to identify the matrix metalloproteases (MMP)
      family members responsible for the phenotype caused by SPOP depletion. Matrigel
      coated invasion chambers were used to detect the invasion ability of SPOP in OS
      cells. RESULTS:   We found that SPOP was down-regulated in clinic OS samples and
      cultured OS cells. Furthermore, we showed that silencing of SPOP promoted cell
      migratory and invasive ability of OS cells in vitro, whereas restored the
      expression of SPOP achieved the opposite effects. At the molecular level, we
      found that SPOP regulated the activity of "PI3K/Akt/NF-kappaB" signaling pathway
      in OS cells. CONCLUSIONS: Our results suggested that down-regulation of SPOP
      promoted OS cells migratory and invasive ability via modulating the "PI3K/Akt/NF
      kappaB" signaling pathway. Thus, SPOP could be a promising drug target for the
      treatment of OS invasion.

PMID- 29461589
TI  - Long non-coding RNA SNHG16 promotes cell growth and metastasis in ovarian cancer.
AB  - OBJECTIVE: To investigate the expression of long non-coding RNA SNHG16 in ovarian
      cancer and to further investigate its role in the development of ovarian cancer
      as well as its potential regulatory mechanism. PATIENTS AND METHODS: Quantitative
      Real-time polymerase chain reaction (qRT-PCR) was used to detect the expression
      of SNHG16 in 103 ovarian cancer tissues and normal tissues; the relationship
      between the expression of SNHG16 and the pathological parameters of ovarian
      cancer and the prognosis of patients was also analyzed. qRT-PCR was used to
      further verify the expression of SNHG16 in the ovarian cancer cells. After
      establishment of SNHG16 knockdown expression model in ovarian cancer cells SKOV-3
      and HO8910 using small interfering RNA, the effect of SNHG16 on biological
      function of ovarian cancer cells was analyzed via cell counting kit-8 (CCK8),
      transwell invasion and migration assay. Finally, its potential mechanism was
      analyzed by Western Blot. RESULTS: qRT-PCR results showed that the expression of
      SNHG16 in ovarian cancer was significantly higher than that in normal tissues,
      and the difference was statistically significant. Compared with patients with
      lower expression of SNHG16, patients with higher expression of SNHG16 had higher
      tumor stage, high rate of distant metastasis and low overall survival rate.
      Compared with the negative control si-NC group, the cell proliferation, invasion
      and migration ability in SNHG16 knockdown group (si-SNHG16) significantly
      decreased. Western Blot showed that after knockdown of SNHG16, expressions of P
      AKT and MMP9 decreased significantly, while there was no significant change in
      the total AKT level. CONCLUSIONS: SNHG16 was highly expressed in ovarian cancer,
      and was correlated with staging, distant metastasis and poor prognosis of ovarian
      cancer. SNHG16 may activate phosphorylation of AKT and upregulate the expression
      of MMP9 to promote cell proliferation, invasion and migration of ovarian cancer.

PMID- 29461590
TI  - Expression and clinical correlation of NGAL and VEGF in endometrial carcinoma.
AB  - OBJECTIVE: To determine the expression of neutrophil gelatinase-associated
      lipocalin (NGAL) and vascular endothelial growth factor (VEGF) in endometrial
      carcinoma. PATIENTS AND METHODS: The clinical features (FIGO staging,
      pathological type, differentiation level, myometrial invasion depth and tumor
      size) and immunostaining analysis of endometrial carcinoma (30 cases), atypical
      hyperplasia (30 cases) and proliferative endometrial tissues (30 cases) were
      analyzed. Immunohistochemistry and reverse transcription PCR (RT-PCR) were
      performed to detect the expression of NGAL and VEGF. RESULTS: The positive tissue
      immunostaining and mRNA expression of NGAL and VEGF in endometrial carcinoma were
      significantly higher than in either atypical hyperplasia or proliferative
      endometrial tissues (p<0.05). The relative expression level of NGAL and VEGF was
      positively correlated with worse FIGO staging, higher differentiation level and a
      greater myometrial invasion depth (p<0.05); but not with patient age,
      pathological type or tumor size (p>0.05). CONCLUSIONS: The abnormal high
      expression of NGAL and VEGF observed in the endometrial carcinoma may be an
      important biomarker for early tumor diagnosis or as a novel target for
      therapeutic intervention.

PMID- 29461591
TI  - Reduced SPOCK1 expression inhibits non-small cell lung cancer cell proliferation
      and migration through Wnt/beta-catenin signaling.
AB  - OBJECTIVE: Accumulating evidence suggests that SPARC/osteonectin, cwcv, and kazal
      like domain proteoglycan 1 (SPOCK1) contributes to the initiation and progression
      of human cancers. However, little is known about the function mechanisms of
      SPOCK1 in non-small cell lung cancer (NSCLC). The aim of this study was to
      investigate the molecular mechanism of SPOCK1 in NSCLC. PATIENTS AND METHODS: The
      expression levels of SPOCK1 in NSCLC tissues and cell lines were analyzed by qRT
      PCR and Western blotting. The proliferative activity of NSCLC cells was
      determined by MTT and colony formation assays. The transwell assay was used to
      examine the cell migration and invasive ability. To study the impact of SPOCK1 on
      Wnt/beta-catenin signaling, we further performed Western blotting for related
      proteins in this pathway. RESULTS: We observed that the expression of SPOCK1 at
      both protein and mRNA levels was also increased in human NSCLC tissues and cell
      lines. Functionally, down-regulation of SPOCK1 in NSCLC cells markedly suppressed
      cell proliferation, colony formation, migration and invasion in vitro.
      Mechanistically, we found that indicated the activation of Wnt/beta-catenin
      pathway was suppressed by SPOCK1 silencing. CONCLUSIONS: The expression of SPOCK1
      served as a tumor promoter, possibly through the Wnt/beta-catenin signaling
      pathway in NSCLC. Targeting SPOCK1 could be a potential therapeutic strategy in
      NSCLC.

PMID- 29461592
TI  - Health-related quality of life and psychosocial implications in testicular cancer
      survivors. A literature review.
AB  - OBJECTIVE: In this review, we focused our attention on Quality of Life (QoL) of
      testicular cancer survivors (TCSs), in general and in the most relevant areas.
      Several key findings have been highlighted in our review. MATERIALS AND METHODS:
      PubMed, MEDLINE and PsycINFO databases were consulted to find published studies,
      from 1980 to May 2017, that met our inclusion criteria. RESULTS: The majority of
      studies investigated older adult TCSs, while few studies on adolescent and young
      adult patients were available. Many studies indicate that health-related QoL
      (HRQoL) is similar among the TCSs and the general population. Even if QoL
      deteriorates so clear at the time of diagnosis and throughout treatment,
      afterward returns to normal levels, as defined by the matched controls. However,
      there are numerous chronic conditions consequent to diagnosis and treatment of
      testicular cancer that plague survivors and affect QoL, like Raynaud-like
      phenomena, peripheral neuropathy, fatigue, anxiety, sexual, fertility and body
      image problems. Even if these problems can have no effects on the measures of
      global QoL, they have an impact on the quality of life. Differences between TCSs
      with and without a partner bring to different outcomes in the adjustments to
      cancer. CONCLUSIONS: It is necessary to identify TCSs with higher risks of poorer
      QoL outcomes, to focus interventions on the areas with the greatest impairments.
      Further researches should consider the effects of testicular cancer on the
      impaired areas, collecting more data to better identify survivor's needs and
      consequent interventions, with a special focus on adolescent and young adult
      TCSs. Other works are requested on therapies, preventive and ameliorative, to
      reduce chronic side effects of testicular cancer treatment.

PMID- 29461593
TI  - Expression of miR-205 in renal cell carcinoma and its association with
      clinicopathological features and prognosis.
AB  - OBJECTIVE: The aim of the present study was to examine the expression of miR-205
      in renal cell carcinoma (RCC) tissue and carcinoma cells; also, we aimed to
      determine the association of miR-205 expression with the clinicopathological
      features and prognosis of RCC, and to explore the mechanism of miR-205. PATIENTS
      AND METHODS: Carcinoma tissue and adjacent normal tissue were collected from 60
      patients with RCC, and the expression of miR-205 was determined by semi
      quantitative PCR, followed by correlation analysis of miR-205 with
      clinicopathological features and prognosis. Subsequently, the human RCC line,
      ACHN, was transfected with miR-205, and the effect of miR-205 overexpression on
      the growth of RCC was examined by MTT assay. Moreover, the effect of miR-205 on
      the migration of colon cancer cells was studied by transwell assay. Additionally,
      immunohistochemistry and Western blot were used to investigate the epithelial
      mesenchymal transition in renal cancer tissue. RESULTS: The expression of miR-205
      was downregulated in RCC tissue compared with adjacent non-cancerous tissue (p <
      0.01). The expression of miR-205 was closely related to the infiltration and
      recurrence of tumors (p < 0.01), but was not correlated with a pathological grade
      or clinical stage (p > 0.05). We also found that overexpression of miR-205 in RCC
      significantly inhibited the growth of cancer cells (p < 0.01) and significantly
      reduced the migration ability (p < 0.01). The epithelial-mesenchymal transition
      occurs in RCC, and miR-205 might inhibit cell proliferation and migration by
      blocking the epithelial-mesenchymal transition. CONCLUSIONS: The expression of
      miR-205 is low in RCC, and may play an important role throughout the progression
      of RCC. Further study of miR-205 may promote the development of a novel
      therapeutic approach for the treatment of RCC.

PMID- 29461594
TI  - The impact of NudCD1 on renal carcinoma cell proliferation, migration, and
      invasion.
AB  - OBJECTIVE: Renal cell carcinoma (RCC) is the most common malignant tumor in the
      urogenital system. Its easily metastatic characteristics greatly reduce the
      postoperative survival rate. NudCD1, as a proto-oncogene, may be involved in the
      proliferation, migration, and invasion of renal cell carcinoma cell. This study
      intends to explore the expression of NudCD1 in renal cancer tissue and its effect
      on renal cell behavior. PATIENTS AND METHODS: NudCD1 expression in RCC tissue was
      tested Western blot. The cellular localization of NudCD1 was detected by
      immunohistochemistry (IHC). NudCD1 highly expressed RCC cell line was selected.
      NudCD1 knockdown or overexpression was performed through cell transfection. Cell
      proliferation, migration, and invasion were assessed by MTT assay, wound scratch
      assay, and transwell assay, respectively. RESULTS: NudCD1 mainly located in the
      cytoplasm and significantly upregulated in RCC tissue compared with adjacent
      normal control (p < 0.05). NudCD1 expressed highest in A498 cell line among
      several RCC cell lines. NudCD1 expression was positively correlated with cell
      proliferation, migration, and invasion in A498. NudCD1 may be treated as a key
      factor in regulating cell behavior. CONCLUSIONS: NudCD1 significantly increased
      in RCC and was positively correlated with cell proliferation, migration, and
      invasion. It could be used as an indicator for the early screening and potential
      treatment target for RCC.

PMID- 29461595
TI  - MiR-1271 negatively regulates AKT/MTOR signaling and promotes apoptosis via
      targeting PDK1 in pancreatic cancer.
AB  - OBJECTIVE: Pancreatic cancer (PC) possesses a very poor prognosis, and its
      pathogenesis is not fully understood. Evidence has suggested that microRNAs play
      important roles in cancer development and progression, the present study was
      designed to study the function of miR-1271 in PC. PATIENTS AND METHODS: PC
      tissues and adjacent normal tissues were collected from 17 patients. MiR-1271 and
      PDK1 expression were quantified by quantitative reverse-transcriptional
      polymerase chain reaction (RT-PCR). AKT/MTOR signaling activity and PDK1 protein
      expression were determined by Western blot. Cell viability and apoptosis were
      assessed by MTT assay and enzyme-linked immunosorbent assay (ELISA). Luciferase
      assay was used to verify whether miR-1271 directly targets PDK1. RESULTS: MiR
      1271 was significantly down-regulated in PC tissues compared with that in the
      paired normal adjacent tissue, and its expression was up-regulated dose
      dependently upon cisplatin treatment in PC cells. Overexpression of miR-1271 in
      these cells produced a pro-apoptotic effect, similar to what caused by cisplatin
      treatment. Moreover, overexpression of miR-1271 inhibited AKT/MTOR signaling,
      which was due to the targeting relationship between miR-1271 and PDK1. Finally,
      knockdown of PDK1 exerted a similar effect on apoptosis to that of miR-1271
      overexpression. CONCLUSIONS: MiR-1271 is a potent tumor suppressor in PC, its pro
      apoptotic function was partially mediated by reduced AKT/MTOR signaling.
      Targeting miR-1271 may represent an effective strategy for PC treatment.

PMID- 29461596
TI  - Association of the upregulation of LncRNA00673 with poor prognosis for colorectal
      cancer.
AB  - OBJECTIVE: To investigate the effect and clinical significance of long non-coding
      RNA 00673 (lncRNA00673) in the occurrence and development of colorectal cancer
      (CRC) through the research on the expression level, biological effect and
      clinical significance of lncRNA00673 in CRC. PATIENTS AND METHODS: The relative
      expression of lncRNA00673 in 71 pairs of CRC tissues and cells was detected by
      quantitative Real-time polymerase chain reaction (qRT-PCR). The correlation of
      the relative expression of lncRNA00673 with the clinicopathological features of
      CRC patients was analyzed. The lncRNA00673 interference sequence was designed and
      synthesized, and its transfection efficiency was detected by qRT-PCR assays. 3
      (4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and clone
      formation experiments were performed to investigate the effect of lncRNA00673 on
      the proliferation ability of CRC cells. RESULTS: In CRC tissues of 71 patients,
      there were 51 patients whose lncRNA00673 level was up-regulated compared with
      that of cancer-adjacent tissues. The highly expressed lncRNA00673 was positively
      correlated with tumor, node and metastasis (TNM) staging, regional lymph node
      metastasis, distant metastasis and tumor size in CRC patients. Cox proportional
      hazards regression model showed that the highly expressed lncRNA00673 was an
      independent risk factor for the overall survival of CRC patients. Kaplan-Meier
      curve analysis showed that highly expressed lncRNA00673 was significantly
      associated with the relatively lower overall survival (OS). MTT and clone
      formation experiments showed that knockdown of lncRNA0673 could inhibit the
      proliferation of CRC cells. CONCLUSIONS: The expression level of lncRNA00673 is
      up-regulated in CRC tissues and cells, which is related to the degree of
      malignancy and poor prognosis. LncRNA00673 can be used as a potential molecular
      marker for the prognosis of CRC.

PMID- 29461597
TI  - The effect and mechanism of metallothionein MT1M on hepatocellular carcinoma
      cell.
AB  - OBJECTIVE: Liver cancer is one of the most common digestive system malignant
      solid tumors. Its incidence and mortality rates keep high, causing serious mental
      and economic burden. So far, the exact mechanism of liver cancer onset has not
      been fully elucidated. Metallothionein (MT) widely exists in various types of
      organisms with highly conserved structure. It contains the short peptide of
      cysteine and sulfur protein with high affinity to heavy metals, including
      cadmium, zinc, and copper. MT1M is an important member of MT family that has been
      verified to participate in regulating hepatocellular carcinoma, thyroid cancer,
      cervical cancer, and other tumors. However, MT1M expression and mechanism in
      hepatoma cells have not been fully elucidated. MATERIALS AND METHODS: Hepatoma
      cell line HepG2 was divided into control and MT1M group. MT1M plasmid was
      constructed and transfected to MT1M group. Real-time PCR was used to test MT1M
      expression. MTT assay was applied to detect HepG2 proliferation. Flow cytometry
      was performed to determine HepG2 apoptosis. Caspase-3 activity was measured.
      Western blot was used to detect Bcl-2 and Bax protein levels. RESULTS: MT1M
      expression significantly increased after MT1M plasmid transfection compared with
      control (p < 0.05). MT1M group showed inhibited HepG2 proliferation, declined
      HepG2 apoptosis, enhanced Caspase-3 activity, reduced Bcl-2 protein level, and
      upregulated Bax protein compared with control (p < 0.05). CONCLUSIONS: MT1M can
      suppress HepG2 proliferation and induce HepG2 apoptosis through downregulating
      Bcl-2, upregulating Bax, and enhancing Caspase-3 activity.

PMID- 29461598
TI  - Association on polymorphisms in LncRNA HOTAIR and susceptibility to HNSCC in
      Chinese population.
AB  - OBJECTIVE: More and more evidence has shown that the critical functions of long
      non-coding RNA (lncRNA) polymorphism in the carcinogenicity mechanism of a
      variety of cancers. The association between lncRNA HOX transcript antisense
      intergenic RNA (HOTAIR) polymorphism and the risk of head and neck squamous cell
      carcinoma (HNSCC) in Chinese population has not been reported. To investigated
      the effects of HOTAIR polymorphism on cancer susceptibility, the influence of
      HOTAIR variants on the risk of HNSCC was analyzed in this study. PATIENTS AND
      METHODS: In this case-control study, the tagging SNPs (rs874945, rs4759314, and
      rs7958904) in HOTAIR gene were genotyped in Chinese population consisting of
      366HNSCC cases and 732 controls. RESULTS: It was found that rs4759314 was
      associated with a significantly increased risk of HNSCC in Chinese population [GG
      vs. AA: adjusted odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.01
      1.50; additive model: OR = 1.21, 95%CI = 1.01-1.46]. However, there were no
      significant associations of rs874945 and rs7958904 with HNSCC risk. CONCLUSIONS:
      HOTAIR rs4759314 may influence HNSCC susceptibility and serve as a diagnostic
      biomarker.

PMID- 29461599
TI  - Microvesicles containing microRNA-21 secreted by proximal tubular epithelial
      cells are involved in renal interstitial fibrosis by activating AKT pathway.
AB  - OBJECTIVE: To investigate the role of microvesicles containing microRNA-21 in
      renal interstitial fibrosis and its possible mechanism. MATERIALS AND METHODS:
      The renal interstitial fibrosis model was established by unilateral ureteral
      obstruction, and proximal tubule epithelial cell line (NRK52E) was used for cell
      model. The phenotype changes of the microvesicles containing microRNA-21 secreted
      by tubule cells during fibrosis were detected, and possible mechanisms
      responsible for the process were also analyzed. RESULTS: During the process of
      renal interstitial fibrosis, microRNA-21 level in the microvesicles secreted by
      tubule cells was increased. The microRNA-21 released from the damaged renal
      tubules inhibited the expression of PTEN and activated the AKT-mTOR signaling
      pathway, thereby exacerbating the renal interstitial fibrosis. CONCLUSIONS:
      MicroRNA-21 secreted by injured proximal tubule epithelial cells participated in
      renal interstitial fibrosis by activating the PTEN/AKT signaling pathway.

PMID- 29461601
TI  - Impact of serum FGF23 levels on blood pressure of patients with chronic kidney
      disease.
AB  - OBJECTIVE: To investigate the impact of serum FGF23 levels on blood pressure of
      patients with chronic kidney disease (CKD). PATIENTS AND METHODS: 128 patients
      with chronic kidney disease were selected from February 2013 to January 2016.
      Using CKD staging method, all the patients were divided into 1 to 5 stages
      according to the glomerular filtration rate. Enzyme-Linked ImmunoSorbent Assay
      (ELISA) was used to detect serum FGF23 levels of CKD patients and healthy control
      subjects. 24 h blood pressure monitoring method was used to monitor the mean
      arterial pressure of patients. Spearman-related analysis method was used to
      statistically analyze serum FGF23 level, mean arterial pressure and glomerular
      filtration rate. RESULTS: The serum FGF23 levels of CKD patients were
      significantly higher than those of the healthy control subjects (p<0.05). Also,
      FGF23 expression levels in serum were positively correlated with mean arterial
      pressure based on the results of the Spearman-related analysis. On the other
      hand, FGF23 expression levels in serum were negatively correlated with glomerular
      filtration rate. The FGF23 expression levels in serum of the patients were
      significantly decreased along with the decrease of mean arterial pressure.
      CONCLUSIONS: Serum FGF23 level is positively correlated with mean arterial
      pressure and negatively correlated with glomerular filtration rate. So, FGF23 has
      an important clinical significance that can reflect blood pressure and treatment
      effect of dialysis of CKD patients.

PMID- 29461600
TI  - Evaluation of the application of high volume hemofiltration in sepsis combined
      with acute kidney injury.
AB  - OBJECTIVE: To investigate the safety and effectiveness of the application of high
      volume hemofiltration (HVHF) in children with sepsis combined with acute kidney
      injury. PATIENTS AND METHODS: A total of 76 child patients were enrolled and
      randomly divided equally (n=38) into control and the observation groups
      respectively. The control group received conventional volume hemofiltration (the
      ultrafiltration rate of 35-50 ml/kg/h), and the observation group received HVHF
      (50-100 ml/kg/h). RESULTS: The serum Interleukin-6 (IL-6), Tumor Necrosis Factor
      a (TNF-alpha) and creatinine levels were significantly lower in the observation
      group than the control group at 6 h, 12 h, 24 h and 48 h of hemofiltration
      (p<0.05). The efficacy rate of treatment was improved. The mortality rate and
      incidence rate of complications were decreased, and the treatment course was
      significantly shortened (p<0.05). CONCLUSIONS: The application of HVHF in
      children with sepsis combined with acute kidney injury has a better safety and
      effectiveness.

PMID- 29461602
TI  - Expression of miR-146a-5p in patients with intracranial aneurysms and its
      association with prognosis.
AB  - OBJECTIVE: The study aims to detect the association of miR-146a-5p with
      intracranial aneurysms (IAs). PATIENTS AND METHODS: The expression of miR-146a-5p
      was compared from plasma samples between 72 patients with intracranial aneurysms
      (IAs) and 40 healthy volunteers by quantitative Real-time polymerase chain
      reaction (qRT-PCR). Statistical analysis was performed to analyze the
      relationship between miR-146a-5p expression and clinical data and overall
      survival (OS) time of IAs patients. Univariate and multivariate Cox proportional
      hazards have also been performed. RESULTS: Notably, higher miR-146a-5p expression
      was found in plasma samples from 72 patients with intracranial aneurysms (IAs)
      compared with 40 healthy controls. Higher miR-146a-5p expression was
      significantly associated with rupture and Hunt-Hess level in IAs patients. Kaplan
      Meier survival analysis verified that higher miR-146a-5p expression predicted a
      shorter overall survival (OS) compared with lower miR-146a-5p expression in IAs
      patients. Univariate and multivariate Cox proportional hazards demonstrated that
      higher miR-146a-5p expression, rupture, and Hunt-Hess were independent risk
      factors of OS in patients with intracranial aneurysms (IAs). CONCLUSIONS: MiR
      146a-5p expression may serve as a biomarker for predicting prognosis in patients
      with IAs.

PMID- 29461603
TI  - Correlations of 25(OH)D level with blood lipid, inflammatory factors and vascular
      endothelial function in diabetic patients.
AB  - OBJECTIVE: To investigate the correlation between 25-hydroxyvitamin D [25(OH)D]
      and the lipid profile, inflammatory cytokines, and endothelial function in
      diabetic patients. PATIENTS AND METHODS: A total of 77 patients with type 2
      diabetes mellitus treated in our hospital from January 2015 to March 2017 and 73
      healthy volunteers were selected. The 25(OH)D, lipids, inflammatory factors, and
      endothelial function were compared between the two groups. The levels of 25(OH)D
      in diabetic patients were also compared to detect the levels of serum lipids and
      inflammatory cytokines in different groups. According to the inflammatory
      factors, patients with diabetes mellitus were divided into several groups. In
      addition, 25(OH)D, endothelial function indicators [nitrogen oxide (NO) and von
      Willebrand factor (vWF)], serum lipids [triglyceride (TG) and total cholesterol
      (TC)], high-density lipoprotein (HDL), and inflammatory factor tumor necrosis
      factor-alpha (TNF-alpha) were compared among different groups. RESULTS: Compared
      with normal group, the 25(OH)D, NO, and HDL in the diabetic group were
      significantly lower than those in the normal group (p<0.05). Other lipids and
      inflammatory factors in the former were significantly higher than those in the
      normal group. Patients have lower HDL in those with less amount of 25(OH)D. Other
      blood lipid components such as TC and TG, LDL, and inflammatory factors
      significantly increased gradually as the 25(OH)D grows (p<0.05). For patients
      with more inflammatory cytokines, levels of 25(OH)D, NO, vWF, and ET-1 were
      significantly lower than those with normal inflammatory cytokines. Correlation
      analysis revealed that 25(OH)D was positively correlated with HDL and NO, but
      negatively correlated with TG, TC, TNF-alpha, and vWF. CONCLUSIONS: In diabetic
      patients, the level of 25(OH)D is decreased and the inflammatory factors are
      increased. In patients with proper supplementation of 25(OH)D, the inflammation
      can be reduced and endothelial function can be improved.

PMID- 29461604
TI  - A novel ultrasound-based vascular calcification score (CALCS) to detect
      subclinical atherosclerosis.
AB  - OBJECTIVE: To quantify non-coronary vascular calcifications (VC) in asymptomatic
      patients at low-intermediate cardiovascular risk by a new color Doppler
      ultrasound (DUS)-based score (the carotid, aortic, lower limbs calcium score,
      CALCs), and to correlate this score with classical parameters associated with
      cardiovascular risk [carotid intima media thickness (IMT), and arterial stiffness
      (AS)]. PATIENTS AND METHODS: All consecutive asymptomatic patients who underwent
      a screening DUS of non-coronary circulation were evaluated and patients at low
      intermediate cardiovascular risk were selected according to Framingham risk score
      (FRS). Among them, we enrolled 70 patients with US evidence of VC and 71 age, sex
      and FRS matched controls. The presence of VC was correlated with classical
      markers of cardiovascular risk, such as AS and intima-media thickness (IMT). AS,
      expressed as pulse wave velocity (PWV) and arterial distensibility, carotid IMT
      and CALCs were measured for both groups. AS and c-IMT were assessed by a new
      Radio-Frequency (RF) DUS-based method. CALCs was generated by our previously
      described B-mode DUS-based method according to number/size of VC in 11 non
      coronary segments (range 0-33). RESULTS: Patients with VC presented higher AS and
      IMT values than controls (PWV 8.34+/-0.98 m/s vs. 6.74+/-0.68 m/s, p<0.0001;
      arterial distensibility 267+/-12 mm vs. 315+/-65 mm, p=0.001; IMT 687+/-132 mm
      vs. 572+/-91 mm, p<0.0001). Mean CALCs of patients with VC was 8.41+/-7.78. CALCs
      were significantly correlated with c-IMT (p<0.0001; r=0.3), PWV (p<0.0001; r=0.4)
      and arterial distensibility (p=0.002; r=-0.1). CONCLUSIONS: DUS-based CALCs is
      highly correlated with other validated markers of subclinical atherosclerosis,
      such as c-IMT and AS. Our results demonstrated the ability of CALCs to identify
      individual predictive factors beyond the traditional risk factors by quantifying
      an interesting and novel step of the atherogenic process. Future studies on
      larger series and with adequate follow up are necessary to confirm these results
      and to evaluate the role of this new marker in monitoring calcific
      atherosclerosis progression.

PMID- 29461605
TI  - MiR-210 protects cardiomyocytes from OGD/R injury by inhibiting E2F3.
AB  - OBJECTIVE: To detect the change in miRNA-210 expression of cardiomyocytes under
      hypoxia/reoxygenation status. Also, the effect of miR-210 on the apoptosis of
      cardiomyocytes induced by oxygen-glucose deprivation/reperfusion (OGD/R) and its
      mechanism through establishing the OGD/R injury model of primary cardiomyocytes
      in this experiment were investigated. MATERIALS AND METHODS: The cell model of
      OGD/R injury was established. The cell apoptosis in each group was detected by
      methyl thiazolyl tetrazolium (MTT) assay and detection of Caspase-3 activity. The
      change in miR-210 expression in each group was detected by Real-time fluorescence
      quantitative polymerase chain reaction (PCR). The high-expression and low
      expression miR-210 models were established through the transient transfection of
      miR-210 mimic and inhibitor to detect the relevant indexes of cell apoptosis. At
      the same time, changes in mRNA and protein expressions of E2F3 were detected by
      RT-PCR and Western blotting, respectively. The E2F3 overexpression vector was
      constructed, and the overexpression vector plasmid and miR-210 mimic were jointly
      transfected into the cells to detect the relevant indexes of cell apoptosis.
      RESULTS: After OGD/R treatment, the activity of Caspase-3 was increased, the
      survival of cardiomyocytes was significantly inhibited and the expression level
      of miR-210 was up-regulated in OGD/R injury. Transfection of miR-210 mimic for
      miR-210 overexpression could alleviate the OGD/R-induced cardiomyocyte injury,
      while the decrease of miR-210 expression could aggravate the apoptosis of
      cardiomyocytes. In addition, the high expression of miR-210 could inhibit the
      protein expression of E2F3, and co-transfection of E2F3 plasmid and miR-210 mimic
      could reverse the inhibiting effect of miR-210 on the apoptosis of
      cardiomyocytes. CONCLUSIONS: We confirmed that miR-210 can inhibit the OGD/R
      induced apoptosis of cardiomyocytes, and miR-210, as an upstream factor, plays a
      protective role in cardiomyocytes through directly inhibiting the protein
      expression of its target gene E2F3.

PMID- 29461606
TI  - Daylight saving time and myocardial infarction: should we be worried? A review of
      the evidence.
AB  - Transitions into and out of Daylight Saving Time (DST) may disrupt circadian
      rhythms and lead to sleep disturbance and deprivation. A first report observed an
      association between DST and acute myocardial infarction (AMI), especially after
      the spring shift and in women. We tried to identify and evaluate the possible
      association between DST and AMI, using the MEDLINE, EMBASE and Google Scholar
      electronic database (years 2009-2016), with regards to the searching terms
      'daylight saving time', 'daylight saving time' plus 'gender', and 'daylight
      saving time' plus 'acute myocardial infarction'. In total, 72, 10, and 6 studies
      were found, respectively. Overall, 6 studies, including a total of 87,994 cases,
      resulted to satisfy the searching request, and were included in the present
      analysis. All studies confirmed a higher occurrence of AMI in the spring shift,
      ranging from 4 to 29%, whereas only 1 study showed a higher occurrence of AMI in
      the autumn shift. By the way, in 5 studies providing separate analysis, the
      results by sex were not univocal. In fact, as for the spring shift, 2 studies did
      not show differences between men and women, 2 reported a higher frequency in men,
      and 1 in women. Regarding the autumn shift, only 1 study reported a higher
      occurrence of AMI in women. These results support the presence of an association
      between DST and a modest increase of AMI occurrence, especially for the spring
      shift, and with no definite gender specific differences.

PMID- 29461607
TI  - Assessment of atrial fibrillation and ventricular arrhythmia risk in patients
      with asthma by P wave/corrected QT interval dispersion.
AB  - OBJECTIVE: Although the relationship between obesity-asthma, obesity-atrial
      fibrillation (AF) and obesity-sudden cardiac death is clearly known, the risk of
      AF and ventricular arrhythmia has not been clearly determined in asthmatic
      patients. The aim of this study was to investigate whether AF, ventricular
      arrhythmia, and sudden cardiac death risk were increased in asthmatic patients
      using P wave dispersion (PWD) and corrected QT interval dispersion (CQTD).
      PATIENTS AND METHODS: The study was designed as a cross-sectional study. A total
      of 164 participants (88 patients with asthma and 76 healthy volunteers) were
      enrolled into the study. PWD and CQTD were measured and recorded in both groups.
      The statistical difference between the two groups was examined. RESULTS: PWD was
      higher in the asthma patients than in control subjects (31.53 +/- 3.18 vs. 30.33
      +/- 3.53, p = 0.023). However, there was no statistically difference between the
      groups in terms of CQTD measurement (43.9 +/- 1.84 vs. 43.63 +/- 2.06, p =
      0.385). In comparison between control group and asthma subgroups (mild, moderate
      and severe), there was a statistically significant difference among these four
      groups in terms of PWD (p = 0.017). Subgroup analyses showed that this difference
      was mainly due to patients with severe asthma. CONCLUSIONS: PWD value was
      elevated in asthmatic compared to the control group. The CQTD was not
      statistically significant between the groups. These results indicate that the
      risk of developing AF in asthmatic patients might be higher than in the normal
      population. Ventricular arrhythmia and sudden cardiac death risk may not be high
      in asthmatic patients.

PMID- 29461608
TI  - High expression of lnc-CRNDE presents as a biomarker for acute myeloid leukemia
      and promotes the malignant progression in acute myeloid leukemia cell line U937.
AB  - OBJECTIVE: To detect the expression of long non-coding RNA-CRNDE in patients with
      acute myeloid leukemia and its effect on proliferation and apoptosis in acute
      myeloid leukemia cell line U937. PATIENTS AND METHODS: 81 cases of newly
      diagnosed acute myeloid leukemia (AML) were enrolled, and 35 non-malignant
      hematological patients were selected as controls. Quantitative RT-PCR (qRT-PCR)
      was performed to detect the expression of lncRNA-CRNDE in the bone marrow
      specimens of the subjects, and the difference between the two groups was also
      compared. The correlation between the expression of lncRNA-CRNDE and the sex,
      age, classification and total survival of clinical patients was analyzed
      according to the clinical data. U937 cells and monocytes isolated from normal
      people were cultured, and the expression of lncRNA-CRNDE in acute myeloid
      leukemia cell line U937 and normal monocytes was compared. SiRNA-CRNDE and pcDNA
      CRNDE were transfected into U937 cells, and cell counting kit-8 (CCK-8) assay was
      performed to detect proliferation of U937 cells, Annexin V/PI flow cytometry was
      carried out to detect cell apoptosis. Cell cycle was measured by flow cytometry.
      RESULTS: The expression of lncRNA-CRNDE in patients with AML and U937 cells was
      significantly higher than that in non-malignant hematological controls. Results
      of clinical data showed that the expression of lncRNA-CRNDE was associated with
      the classification and total survival of myeloid leukemia in clinical patients.
      After transfection of siRNA-CRNDE, the proliferation and cloning ability of U937
      cells decreased, while the apoptosis increased (p < 0.01) and cells were arrested
      in G0-G1 phase. Meanwhile, after transfection of pcDNA-CRNDE, the proliferation
      ability of U937 cells increased significantly, which indicated that the
      expression of lncRNA-CRNDE might play an essential role in promoting the
      proliferation of U937 cells. CONCLUSIONS: LncRNA-CRNDE is highly expressed in the
      bone marrow tissues of AML patients, and the expression level is negatively
      correlated with the total survival of those clinical patients. Meanwhile, the
      expression is higher in FAB type M4 and M5 than that in M1, M2 and M3. LncRNA
      CRNDE promotes the proliferation and cell cycle of U937 cells, and inhibits cell
      apoptosis, which is expected to become a molecular marker for predicting and
      treating AML.

PMID- 29461609
TI  - The effects of recombinant human growth hormone (rHGH) on survival of slender
      narrow pedicle flap and expressions of vascular endothelial growth factor (VEGF)
      and classification determinant 34 (CD34).
AB  - OBJECTIVE: To explore the effects of recombinant human growth hormone (rHGH) on
      the survival of the mouse slender narrow pedicle flap and the expressions of
      vascular endothelial growth factor (VEGF) and classification determinant 34
      (CD34). MATERIALS AND METHODS: A total of 20 BALB/c mice were randomly divided
      into the experimental group (n=10) and control group (n=10). The flaps were
      transplanted for mice in two groups respectively. 6 h after the operation, the
      mice in the experimental group were administrated with rHGH via local
      subcutaneous injection, while the mice in the control group were injected with
      the same amount of normal saline. The laser Doppler was used to measure the sub
      flap blood flow rates before the operation, and 3 days, 7 days and 14 days after
      the operation, respectively; the flap necrosis and survival areas of mice in two
      groups were measured respectively, and the survival rate of the flap was
      calculated 14 days after the operation. Afterwards, the flaps of mice in two
      groups were exfoliated and the shape and structure of flap tissues were tested by
      the hematoxylin-eosin (HE) staining. Reverse transcription-polymerase chain
      reaction (RT-PCR) and Western blot were used to test the levels of mRNA and
      protein of VEGF and CD34 in the flap tissues. RESULTS: The flaps of mice in the
      control group mainly exhibited the black or grayish-black and lost the elasticity
      with the hard texture, while those in the experimental group were ruddy in color
      with favorable elasticity. The survival rate of flaps of mice in the experimental
      group was significantly higher than that in the control group (83.61 +/- 12.56%
      vs. 46.25 +/- 9.70%) and the necrosis area of flaps of mice in the experimental
      group was significantly smaller than that in the control group (1.32 +/- 0.16 vs.
      4.13 +/- 0.35, p < 0.05). There were no statistical differences in the blood flow
      rates of mouse flap both before the operation and three days after the operation
      between two groups (p > 0.05), while the blood flow rates of mouse flap both 7
      days and 3 days after the operation in the experimental group were higher than
      those in the control group (p > 0.05). Compared with those in the control group,
      the levels of VEGF and CD34 were significantly increased, but the levels of the
      inflammatory factors of the interleukin-6 (IL-6) and tumor necrosis factor-alpha
      (TNF-alpha) were significantly decreased (p < 0.05). CONCLUSIONS: rHGH plays an
      active role in the survival of the flap through promoting the angiogenesis and
      inhibiting inflammatory reaction.

PMID- 29461610
TI  - The effect of DC+CIK combined therapy on rat liver cancer model and its
      modulatory effect on immune functions.
AB  - OBJECTIVE: Primary liver cancer is a sort of the most common solid tumors
      occurred in the digestive system. The incidence and mortality rate maintain at a
      high level, thus leading to heavy economic and psychological burdens for
      patients. Next-generation biological therapy, such as cellular immune treatment,
      improves the medicine efficacy. Cytokine-induced killer (CIK) cells can
      effectively clear residual tumor lesion and inhibit metastasis or recurrence.
      Dendritic cells (DCs) can specifically eliminate tumor cells via modulating
      cellular immune function of the host. This study aimed to investigate the
      function of DC+CIK combined treatment on rat liver model and its effect on immune
      functions. MATERIALS AND METHODS: RH-35 tumor cell was used to prepare live
      cancer model on Wistar rats, which were further divided into control, CIK and
      DC+CIK groups, in which rats received autograft CIK and DCs. Tumor size was later
      measured along with liver function index. The secretions of IFN-gamma, IL-4, and
      TNF-alpha were measured by Real-time PCR and Western blotting. RESULTS: Both CIK
      and DC+CIK treatment significantly reduced tumor size and improved liver
      function, increased secretion of IFN-gamma, IL-4, and TNF-alpha, decreased Bcl-2
      expression and enhanced Bax expression (p < 0.05 compared to control group).
      DC+CIK combined therapy presented significantly better efficacy than CIK did.
      CONCLUSIONS: DC+CIK combined therapy can protect the host against tumors invasion
      via modulating body immune or liver function, regulating apoptosis/anti-apoptosis
      balance, which shows better efficacy than CIK alone, and can work as a novel
      biological therapeutic strategy for liver cancer.

PMID- 29461611
TI  - Leptin inhibits apoptosis of nucleus pulposus cells via promoting autophagy.
AB  - OBJECTIVE: To investigate whether leptin can regulate the apoptosis of nucleus
      pulposus cells by adjusting the autophagy of human degenerative nucleus pulposus
      cells and its possible molecular mechanism. PATIENTS AND METHODS: The human
      degenerative nucleus pulposus cells were extracted and cultured, then treated
      with leptin, leptin inhibitor and leptin neutralizing antibody; the expressions
      of light chain 3 (LC3) II/I and Beclin-1 were detected by Western blot, and the
      change of apoptosis rate was detected by flow cytometer. After the nucleus
      pulposus cells were treated with leptin, bafilomycin A, the autophagy inhibitor,
      was used to inhibit the autophagy. Western blot was used to detect the
      expressions of LC3II/I and cleaved caspase 3, and the apoptosis rate was detected
      by flow cytometer. Finally, Western blot was used to detect the expressions of
      Akt and extracellular regulated protein kinases 1/2 (Erk1/2) signal pathway
      associated proteins after nucleus pulposus cells were treated with LY294002, the
      phosphatidylinositol 3-kinase (PI3K) inhibitor, and PD98059, the extracellular
      regulated protein kinases (MEK) inhibitor. RESULTS: After the cells were treated
      with leptin, the expressions of LC3II/I and Beclin-1 could be increased, and the
      apoptosis rate of nucleus pulposus cells could be decreased (p<0.05). After the
      degenerative nucleus pulposus cells were treated with leptin inhibitor or
      neutralizing antibody, the expressions of LC3II/I and Beclin-1 were decreased,
      and the apoptosis rate of nucleus pulposus cells was increased (p<0.05).
      Bafilomycin A could increase the expression of LC3II/I (p<0.05), increase the
      apoptosis rate (p<0.05), and offset the effect of leptin of decreasing the
      apoptosis rate of nucleus pulposus cells. The results of Western blot showed that
      LY294002 could inhibit the expression of LC3II/I by inhibiting the Akt
      phosphorylation (p<0.05), but leptin could partially offset the inhibiting effect
      of LY294002 on the expression of LC3II/I. PD9805 could partially decrease the
      expression of LC3II/I via inhibiting the Erk1/2 phosphorylation, but leptin could
      not reverse the inhibiting effect of PD98059 on the expression of LC3II/I.
      CONCLUSIONS: Leptin inhibits the apoptosis of degenerative nucleus pulposus cells
      via promoting autophagy, and leptin regulates the autophagy of human degenerative
      nucleus pulposus cells through the phosphorylated Erk1/2 signal.

PMID- 29461612
TI  - The hyperthermic intraoperative intraperitoneal chemotherapy in the treatment of
      advanced abdominopelvic cancer. Personal experience on 103 procedures during a
      seventeen year period in a single Italian center.
AB  - OBJECTIVE: Integration of different therapeutic strategies in cancer surgery in
      the last years has led from treating primary lesions to the surgical treatment of
      metastases. The purpose of this paper is to report a single Italian center
      experience of treatment of peritoneal carcinosis of the abdominopelvic
      malignancies. PATIENTS AND METHODS: 103 HIPEC procedures were performed in 17
      years on 94 selected patients affected by abdominopelvic cancer. The PCI score
      was calculated at laparotomy. The CC score was calculated before doing HIPEC.
      HIPEC was carried out according to the Coliseum technique. RESULTS: The surgical
      cytoreduction allowed 89 patients to be subjected to HIPEC treatment with a CC
      score 0; 9 patients with a CC 1; 3 patients with a CC 2 and 2 patients with a CC
      3. In 22 patients postoperative complications were recorded. No operative
      mortality occurred. The median follow-up of 53 months shows a rate of survival
      equivalent to 49 %, with a relapse in 46 patients, 29 of them reached exitus.
      CONCLUSIONS: The surgical resection alone for patients affected by advanced
      cancer with peritoneal carcinomatosis cannot be considered a sufficient treatment
      any longer and HIPEC would help to prolong survival in these patients.

PMID- 29461613
TI  - Paraquat promotes the epithelial-mesenchymal transition in alveolar epithelial
      cells through regulating the Wnt/beta-catenin signal pathway.
AB  - OBJECTIVE: To investigate whether paraquat (PQ)-induced rat alveolar type II
      cells (RLE-6TN) epithelial-mesenchymal transition (EMT) and to explore the
      underlying molecular mechanism. MATERIALS AND METHODS: In the present study, RLE
      6TN cells were treated by 20 MUmol/L PQ, and then the morphology was observed
      under an inverted microscope; RT-PCR and Western blot were performed to detect
      the expression level of EMT related markers, E-cadherin, and vimentin, as well as
      Wnt/beta-catenin signaling pathway. In addition, we performed the transwell
      invasion assay to detect the ability of cell invasion. RESULTS: We demonstrated
      that PQ was able to induce the transition of RLE-6TN cells from epithelial
      morphology to fibroblast-like morphology, associated with the acquisition of
      migratory properties. Phenotypically, PQ induced-EMT was characterized by loss of
      epithelial cell markers including E-cadherin, while upregulation of mesenchymal
      cell markers including vimentin, was concurrent with the activation of Wnt/beta
      catenin signaling pathway. Furthermore, knockdown of beta-catenin by using
      specific siRNA could reverse PQ triggered EMT process and attenuated cell
      migration ability. CONCLUSIONS: PQ promotes RLE-6TN epithelial-mesenchymal
      transition by upregulating the expression of Wnt/beta-catenin.

PMID- 29461614
TI  - Mitochondria-mediated disturbance of fatty acid metabolism in proximal tubule
      epithelial cells leads to renal interstitial fibrosis.
AB  - OBJECTIVE: To investigate the role of mitochondria-mediated fatty acid metabolism
      in proximal tubule cells in renal interstitial fibrosis. MATERIALS AND METHODS:
      Intraperitoneal injection of folate was performed to induce renal interstitial
      fibrosis in mice. Polymerase chain reaction (PCR) was used to detect the
      expression of cytochrome c oxidase subunit IV (COX4IL) and phosphoenolpyruvate
      carboxykinase 1 (PCK1) in samples. Electron microscope was used to detect the
      activity of mitochondria. Serum creatinine and urea nitrogen were chosen as
      evaluation criteria for renal function. Western-blotting was used to detect
      protein expression of cells. Immunohistochemistry was used to test renal
      structure and deposition of collagen. RESULTS: In renal interstitial fibrosis,
      mitochondria mediated the dysfunction and the promotion of tubulointerstitial
      fatty acid metabolism. Besides, it could also reduce renal interstitial fibrosis
      and alleviate the fatty acid metabolism of tubulointerstitial fibrosis.
      CONCLUSIONS: Mitochondrial dysfunction induced fatty acid metabolism is an
      important factor to promote the progress of renal interstitial fibrosis.
      Intervention of related targets of fatty acid metabolism is expected to become a
      new treatment for renal interstitial fibrosis.

PMID- 29461615
TI  - Bilastine safety in drivers who need antihistamines: new evidence from high-speed
      simulator driving test on allergic patients.
AB  - OBJECTIVE: Bilastine is a highly selective, non-sedating antihistamine, indicated
      for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria.
      Available data suggest that bilastine interferes neither with driving ability nor
      with flying-related performance. However, no data are available on the effect of
      bilastine on the driving ability in extreme conditions. Here we analyzed the
      effect of 7 days treatment with 20 mg bilastine in patients with allergic
      rhinitis and/or chronic urticaria, on psychophysical performance assessed by the
      Formula One (F1) high-speed simulator-driving test. PATIENTS AND METHODS: This
      study is a phase IV, interventional, prospective, mono-centric, single arm, open
      label trial. Eighteen outpatients affected by allergic rhinitis and/or chronic
      urticaria, able to perform a preliminary driving test on F1 simulator were
      considered (V-1). First, the patients had a screening visit to assess their
      eligibility (V0). Visit 1 (V1), at the end of placebo before bilastine treatment
      and Visit 2 (V2), at the end of bilastine treatment. The primary variable
      parameter was the ability to maintain the vehicle in a central position at
      different speeds (50, 150, and 250 km/h). RESULTS: Bilastine had a good safety
      profile and was well tolerated in terms of adverse events, laboratory parameters
      and vital signs. Bilastine did not have any negative effect on the ability to
      maintain the requested path, a constant speed as well as on attention and
      reactivity levels, even in extreme driving conditions. CONCLUSIONS: This study is
      the first done in patients with allergic rhinitis and/or chronic urticaria using
      a F1-high speed simulator-driving test evaluating subjects' performance under
      bilastine treatment.

PMID- 29461616
TI  - Leukotriene receptor antagonists do not improve lung function decline in COPD: a
      meta-analysis.
AB  - OBJECTIVE: Leukotriene receptor antagonists (LTRA), the anti-inflammatory agents,
      have been reported new therapeutic value in chronic obstructive pulmonary disease
      (COPD). However, the effects of LTRA on lung function decline in COPD were
      determined with inconsistent results and a meta-analysis is needed. MATERIALS AND
      METHODS: Published cohort or randomized controlled studies were retrieved from
      PubMed and Embase databases. RESULTS: Pooled standardized mean difference (SMD)
      with 95% confidence interval (CI) was calculated in a random effects model. Six
      studies involving 221 COPD patients were included. Pooled effect size showed no
      significant improvements in FEV1 (SMD: 0.28, 95% CI: -0.17 to 0.72, p=0.227), FVC
      (SMD: 0.54, 95% CI: -0.10 to 1.18, p=0.597) and FEV1/FVC (SMD: 0.18, 95% CI: 
      0.09 to 0.46, p=0.189) in COPD patients after LTRA treatment. In subgroup
      analysis, neither short-term (<1 year) (SMD: 0.47, 95% CI: -0.06 to 0.99,
      p=0.082) nor long-term (>=1 year) (SMD: -0.13, 95% CI: -0.57 to 0.31, p=0.561)
      LTRA exposure could benefit lung function decline in COPD. CONCLUSIONS: This meta
      analysis suggests neither short-term nor long-term exposure of LTRA can improve
      lung function decline in COPD. However, large scale randomized controlled trials
      are urgently warranted.

PMID- 29461617
TI  - JAK/STAT5 signaling pathway inhibitor ruxolitinib reduces airway inflammation of
      neutrophilic asthma in mice model.
AB  - OBJECTIVE: The aim of this study was to explore the role of JAK/STAT signaling
      pathway inhibitor Ruxolitinib in neutrophilic airway inflammation and its
      possible immunological mechanism. MATERIALS AND METHODS: A total of 60 female
      C57BL/6 mice were randomly divided into neutrophilic asthma (NA) group,
      Ruxolitinib-treated (Ruxo) group and control (Con) group. Mice in NA and Ruxo
      groups were sensitized with ovalbumin (OVA) and excited to establish mice models
      of asthma. Bronchoalveolar lavage fluid (BALF) was collected at 24 h after the
      last atomization, and the total number of karyocyte and the percentages of sorted
      cells were detected. The activity of interleukin-17 (IL-17) in BALF was detected
      by enzyme-linked immunosorbent assay (ELISA). Lung tissue was separated and
      subjected to hematoxylin-eosin (HE) staining, and the pathological changes of
      lung tissue were observed under an optical microscope. The proportion of T helper
      17 (Th17) cells in the lung was detected by flow cytometry (FCM). After
      successful modeling of NA mice, immunomagnetic bead purified mouse splenic
      cluster of differentiation 4+(CD4+) T was treated with IL-7 and Ruxolitinib, and
      the proportion of differentiated Th17 cells to CD4+ T cells and Ki-67, B-cell
      lymphoma 2 (Bcl-2) and activated Caspase3 expressions in Th17 cells were detected
      via FCM. RESULTS: Compared with those in NA group, the number of karyocytes and
      the percentages of neutrophils (NEU) and eosinophils (EOS) in BALF in Ruxo group
      were significantly reduced. The pathological changes of lung tissue in Ruxo group
      were overtly less than those in NA group. In comparison with NA group, Ruxo group
      had decreased IL-17A level in BALF and reduced proportion of Th17 cells in lung
      tissue. In in vitro experiment, compared with those in Con group, decreased
      percentages of Ki-67 and Bcl-2 proteins and increased percentage of Caspase3 in
      Th17 cells were found in Ruxo group. CONCLUSIONS: Ruxolitinib may suppress the
      survival of Th17 cells by inhibiting the JAK/STAT5 signaling pathway and regulate
      the anti-apoptosis proteins Bcl-2 and Caspase3, thus promoting the increase of
      Thl7 cells entering the apoptotic pathway and reducing airway inflammation in NA
      mice.

PMID- 29461618
TI  - TMS as tool to investigate the effect of pharmacological medications on cortical
      plasticity.
AB  - The application of medications with a well-defined mode of action on a
      neurotransmitter or neuromodulator of the central nervous system (CNS) can be
      utilized to test the pharmaco-physiological properties of transcranial magnetic
      stimulation (TMS) on cortical excitability and plasticity. Similarly, a
      physiologically well-defined TMS measure of cortical excitability may be
      exploited to study a particular drug's effect at the level of the cerebrum. In
      this review, we aim to assess the impact of calcium channel blockers, Selective
      Serotonin Reuptake Inhibitors (SSRIs), and GABAergic agents on cortical
      excitability and plasticity while concurrently investigating how TMS can enhance
      this understanding. We will begin by reviewing the basics of neuroplasticity, as
      explored in animal experimentation, and relate this to our knowledge about
      neuroplasticity induced in humans by TMS techniques. We will then discuss
      pharmacological modulation of plasticity in humans. Finally, we will review
      abnormalities of plasticity inherent to certain neuropsychiatric diseases and
      discuss how the combination of TMS with pharmacological intervention can augment
      our knowledge of the pathophysiology of these diseases and guide purposeful
      treatment.

PMID- 29461619
TI  - MicroRNA-200c suppressed cervical cancer cell metastasis and growth via targeting
      MAP4K4.
AB  - OBJECTIVE: To dissect the functioning mode of miR-200c on cervical cancer cell
      metastasis and growth and provide therapeutic targets for cervical cancer.
      PATIENTS AND METHODS: By quantitative Real-time polymerase chain reaction, the
      miR-200c expression level in 42 pairs of cervical cancer tissue samples and six
      cervical cancer-derived cell lines were examined. Using miR-200c mimics, we
      analyzed the effects of miR-200c over-expression on cell proliferation, invasion,
      and migration. Dual-luciferase activity assay was recruited to examine the
      potential target gene MAP4K4 that predicted by several databases. Protein level
      was studied using Western blot. RESULTS: miR-200c expressed significantly lower
      in cervical cancer tissue samples and cell lines. And over-expression of miR-200c
      in cervical cancer cells significantly decreased the cell invasion, migration and
      proliferation abilities. Dual-luciferase and Western blot confirmed MAP4K4 as a
      target gene of miR-200c. Furthermore, up-regulation of MAP4K4 counteracted the
      suppressive effect of miR-200c over-expression on cell growth and metastasis.
      CONCLUSIONS: miR-200c could suppress cervical cancer cell proliferation and
      progression via regulating MAP4K4, which might provide a new target for cervical
      cancer diagnosis and therapy.

PMID- 29461620
TI  - Developing a Core Outcome Set for Trials to Improve Medication Use: Guidelines or
      Guidance?

PMID- 29461621
TI  - Core Outcome Set for Trials Aimed at Improving the Appropriateness of
      Polypharmacy in Older People in Primary Care.
AB  - OBJECTIVES: To develop a core outcome set (COS) for use in effectiveness trials
      of interventions aiming to improve the appropriateness of polypharmacy in older
      people in primary care. DESIGN: Standard COS development methodology was
      followed, comprising identification of outcomes of studies from an update of a
      Cochrane systematic review and previously collected qualitative data and an
      online Delphi consensus exercise involving three rounds. PARTICIPANTS: An
      international panel of 160 stakeholders comprising 120 healthcare experts and a
      public participant panel of 40 older people. MEASUREMENTS: Outcomes identified
      from studies included in the Cochrane review and secondary analysis of previously
      collected qualitative data were scored on a 9-point Likert scale using the GRADE
      scoring system anchored at 1 (not important) and 9 (critical). Consensus criteria
      for the COS were defined as 70% or more of participants scoring the outcome as
      critical and 15% or fewer scoring the outcome as not important. RESULTS: Twenty
      nine outcomes identified from the Cochrane review and existing qualitative data
      were included in the Delphi exercise. The final COS comprised 16 outcomes. The 7
      highest-ranked outcomes were serious adverse drug reactions, medication
      appropriateness, falls, medication regimen complexity, quality of life,
      mortality, and medication side effects. CONCLUSION: A COS for interventions
      aiming to improve the appropriateness of polypharmacy for older people in primary
      care has been developed. Future work will focus on identifying appropriate tools
      to measure.

PMID- 29461622
TI  - Fidelity of motivational interviewing in an American Indian oral health
      intervention.
AB  - OBJECTIVES: Assess fidelity of a motivational interviewing (MI) intervention
      focused on preventing early childhood caries in a cohort of American Indian
      mothers with newborns. METHODS: Four interventionists were trained to administer
      an oral health MI intervention. The MI sessions were audio recorded to enable
      scoring as part of fidelity studies to assess the interventionist's degree of
      competence in using MI principles. Evaluation of the interventionists was
      completed using the Motivational Interviewing Treatment Integrity (MITI) 3.1.1.
      which assesses global ratings and behaviour counts. Two reviewers evaluated and
      scored the MI sessions; a random sample of twenty per cent of the total
      interviews was scored by a trained reviewer and fifty per cent of the randomly
      selected files scored by an external expert. A total of 225 files were coded by
      the trained reviewer and 121 files by the external expert. RESULTS: Mean global
      scores for all interventionists combined were around 4.0 (expert competence).
      Scores for reflection to question ratios (around 0.6) were below beginner
      competence. Scores ranged from beginner to expert competence for open-ended
      questions (54%-56%), complex reflections (38%-43%) and MI-adherent statements
      (93%-95%). There was variation in competence for the four interventionists when
      analysed individually. Inter-rater reliability scores for the two reviewers
      ranged from fair (0.40-0.59) to good (0.60-0.74). The MI interventionist rated
      the best in the fidelity assessment had the worst study outcomes compared to
      other interventionists. CONCLUSIONS: Individual interventionists' scores for the
      MITI global ratings and behaviour counts reflected variation in competence and
      ranged from below beginner to expert levels. A higher competence level of the
      interventionist as assessed by the fidelity study was not related to better study
      outcomes.

PMID- 29461623
TI  - Determination of homogentisic acid in urine for diagnosis of alcaptonuria:
      Capillary electrophoretic method optimization using experimental design.
AB  - Homogentisic acid (HGA) is a diagnostic metabolite that accumulates in the urine
      and tissues of patients with alkaptonuria which is a rare autosomal recessive
      disease. HGA is a specific metabolite in urine and serum, which is used for
      diagnosis of alkaptonuria. This study presents an inexpensive and easy capillary
      electrophoretic method for the quantitative determination of HGA in urine
      samples. The method was optimized using full factorial experimental design. The
      optimal separation electrolyte and separation voltage were revealed as 45 mmol/L
      phosphate buffer at pH 7.0 and 22 kV, respectively. Under these conditions the
      presence of HGA was detected in 6 min. Repeatability of migration times and
      corrected peak areas of HGA (as RSD) were 0.37 and 1.99, respectively. The
      detection limit was 0.56 MUg/mL, 3 times of the average noise, and the
      quantification limit was 1.85 MUg/mL, 10 times the average noise for HGA. Urine
      samples were directly injected to the capillary without any pretreatment step.

PMID- 29461624
TI  - The Walking Corpse Syndrome: Geriatrics and the Electronic Health Record.

PMID- 29461626
TI  - Investigating societal determinants of oral health-Opportunities and challenges
      in multilevel studies.
AB  - The high prevalence of oral diseases and the persistent nature of socioeconomic
      inequalities in oral health outcomes across societies presents a significant
      challenge for public health globally. A debate exists in epidemiology on the
      merits of investigating population variations in health and its determinants over
      studying individual health and its individual risk factors. The choice of
      analytical unit for health outcomes at the population level has policy
      implications and consequences for the causal understanding of population-level
      variations in health/disease. There is a lack of discussion in oral epidemiology
      on the relevance of studying population variations in oral health. Evidence on
      the role of societal factors in shaping variations in oral health at both the
      individual level and the population level is also mounting. Multilevel studies
      are increasingly applied in social epidemiology to address hypotheses generated
      at different levels of social organization, but the opportunities offered by
      multilevel approaches are less applied for studying determinants of oral health
      at the societal level. Multilevel studies are complex as they aim to examine
      hypotheses generated at multiple levels of social organization and require
      attention to a range of theoretical and methodological aspects from the stage of
      design to analysis and interpretation. This discussion study aimed to highlight
      the value in studying population variations in oral health. It discusses the
      opportunities provided by multilevel approaches to study societal determinants of
      oral health. Finally, it reviews the key methodological aspects related to
      operationalizing multilevel studies of societal determinants of oral health.

PMID- 29461627
TI  - Myasthenia gravis with muscle-specific tyrosine kinase antibodies: A narrative
      review.
AB  - Growing evidence provides new insights about myasthenia gravis (MG) with
      antibodies against muscle-specific tyrosine kinase (MuSK-MG), including its
      pathogenesis, clinical and electrophysiological manifestations, and treatment.
      Data now support the presence of both presynaptic and postsynaptic dysfunction in
      MuSK-MG. This is 1 of many key differences between MuSK-MG and acetylcholine
      receptor antibody-MG (AChR-MG), especially as it pertains to potential
      therapeutic implications. In comparison to AChR-MG, MuSK-MG is generally more
      refractory to treatment. However, because MuSK-MG is better understood and more
      readily recognized today, there are more reports of a relatively benign course.
      The most effective immunotherapies for MuSK-MG are corticosteroids,
      plasmapheresis, and rituximab. With appropriate therapy, most patients with MuSK
      MG achieve minimal manifestation status or better on the postintervention status
      outlined by the Myasthenia Gravis Foundation of America. A minority of patients
      remain refractory to treatment, and optimal management for this group remains a
      considerable challenge. Muscle Nerve 58: 344-358, 2018.

PMID- 29461625
TI  - Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy:
      Targeting the source.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side
      effect of many chemotherapeutic agents, affecting >60% of patients with cancer.
      Moreover, CIPN persists long into survivorship in approximately 20% to 30% of
      these patients. To the authors' knowledge, no drugs have been approved to date by
      the US Food and Drug Administration to effectively manage chemotherapy-induced
      neuropathic pain. The majority of the drugs tested for the management of CIPN aim
      at symptom relief, including pain and paresthesia, yet are not very efficacious.
      The authors propose that there is a need to acquire a more thorough understanding
      of the etiology of CIPN so that effective, mechanism-based, disease-modifying
      interventions can be developed. It is important to note that such interventions
      should not interfere with the antitumor effects of chemotherapy. Mitochondria are
      rod-shaped cellular organelles that represent the powerhouses of the cell, in
      that they convert oxygen and nutrients into the cellular energy "currency"
      adenosine triphosphate. In addition, mitochondria regulate cell death. Neuronal
      mitochondrial dysfunction and the associated nitro-oxidative stress represent
      crucial final common pathways of CIPN. Herein, the authors discuss the potential
      to prevent or reverse CIPN by protecting mitochondria and/or inhibiting nitro
      oxidative stress with novel potential drugs, including the mitochondrial
      protectant pifithrin-MU, histone deacetylase 6 inhibitors, metformin,
      antioxidants, peroxynitrite decomposition catalysts, and anti-inflammatory
      mediators including interleukin 10. This review hopefully will contribute toward
      bridging the gap between preclinical research and the development of realistic
      novel therapeutic strategies to prevent or reverse the devastating neurotoxic
      effects of chemotherapy on the (peripheral) nervous system. Cancer 2018;124:2289
      98. (c) 2018 American Cancer Society.

PMID- 29461628
TI  - A cytochrome P450 CYP71 enzyme expressed in Sorghum bicolor root hair cells
      participates in the biosynthesis of the benzoquinone allelochemical sorgoleone.
AB  - Sorgoleone, a major component of the hydrophobic root exudates of Sorghum spp.,
      is probably responsible for many of the allelopathic properties attributed to
      members of this genus. Much of the biosynthetic pathway for this compound has
      been elucidated, with the exception of the enzyme responsible for the catalysis
      of the addition of two hydroxyl groups to the resorcinol ring. A library prepared
      from isolated Sorghum bicolor root hair cells was first mined for P450-like
      sequences, which were then analyzed by quantitative reverse transcription
      polymerase chain reaction (RT-qPCR) to identify those preferentially expressed in
      root hairs. Full-length open reading frames for each candidate were generated,
      and then analyzed biochemically using both a yeast expression system and
      transient expression in Nicotiana benthamiana leaves. RNA interference (RNAi)
      mediated repression in transgenic S. bicolor was used to confirm the roles of
      these candidates in the biosynthesis of sorgoleone in planta. A P450 enzyme,
      designated CYP71AM1, was found to be capable of catalyzing the formation of
      dihydrosorgoleone using 5-pentadecatrienyl resorcinol-3-methyl ether as
      substrate, as determined by gas chromatography-mass spectroscopy (GC-MS). RNAi
      mediated repression of CYP71AM1 in S. bicolor resulted in decreased sorgoleone
      contents in multiple independent transformant events. Our results strongly
      suggest that CYP71AM1 participates in the biosynthetic pathway of the
      allelochemical sorgoleone.

PMID- 29461629
TI  - Development and validation of a LC-MS/MS method for quantitation of fosfomycin -
      Application to in vitro antimicrobial resistance study using hollow-fiber
      infection model.
AB  - Extensive use and misuse of antibiotics over the past 50 years has contributed to
      the emergence and spread of antibiotic-resistant bacterial strains, rendering
      them as a global health concern. To address this issue, a dynamic in vitro hollow
      fiber system, which mimics the in vivo environment more closely than the static
      model, was used to study the emergence of bacterial resistance of Escherichia
      coli against fosfomycin (FOS). To aid in this endeavor we developed and validated
      a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for
      quantitative analysis of FOS in lysogeny broth. FOS was resolved on a Kinetex
      HILIC (2.1 * 50 mm, 2.6 MUm) column with 2 mm ammonium acetate (pH 4.76) and
      acetonitrile as mobile phase within 3 min. Multiple reaction monitoring was used
      to acquire data on a triple quadrupole mass spectrometer. The assay was linear
      from 1 to 1000 MUg/mL. Inter- and intra-assay precision and accuracy were <15%
      and between +/-85 and 115% respectively. No significant matrix effect was
      observed when corrected with the internal standard. FOS was stable for up to 24 h
      at room temperature, up to three freeze-thaw cycles and up to 24 h when stored at
      4 degrees C in the autosampler. In vitro experimental data were similar to the
      simulated plasma pharmacokinetic data, further confirming the appropriateness of
      the experimental design to quantitate antibiotics and study occurrence of
      antimicrobial resistance in real time. The validated LC-MS/MS assays for
      quantitative determination of FOS in lysogeny broth will help antimicrobial drug
      resistance studies.

PMID- 29461630
TI  - Factors Affecting Discharge to Home of Geriatric Intermediate Care Facility
      Residents in Japan.
AB  - OBJECTIVES: To investigate factors associated with lower likelihood of discharge
      to home from geriatric intermediate care facilities in Japan. DESIGN:
      Retrospective cohort study. SETTING: We used data from the nationwide long-term
      care (LTC) insurance claims database (April 2012-March 2014). PARTICIPANTS: Study
      participants were 342,758 individuals newly admitted to 3,459 geriatric
      intermediate care facilities during the study period. MEASUREMENTS: The primary
      outcome was discharge to home. We performed a multivariable competing-risk Cox
      regression with adjustment for resident-, facility-, and region-level
      characteristics. Resident level of care needs and several medical conditions were
      included as time-varying covariates. Death, admission to a hospital, and
      admission to another LTC facility were treated as competing risks. RESULTS:
      During the 2-year follow-up period, 19% of participants were discharged to home.
      In the multivariable competing-risk Cox regression, the following factors were
      significantly associated with lower likelihood of discharge to home: older age,
      higher level of care need, having several medical conditions, private ownership
      of the facility, more beds in the facility, and more LTC facility beds per 1,000
      adults aged 65 and older in the region. CONCLUSION: Only 19% of residents were
      discharged to home. Our results are useful for policy-makers to promote discharge
      to home of older adults in geriatric intermediate care facilities.

PMID- 29461631
TI  - A Gift From Mary.

PMID- 29461632
TI  - Higher mortality of adults with asthma: A 15-year follow-up of a population-based
      cohort.
AB  - BACKGROUND: Higher all-cause mortality in asthmatics has been shown previously.
      Polysensitization is associated with higher morbidity among asthmatic children,
      and allergic rhinitis and/or allergic conjunctivitis (AR/AC) are associated with
      higher morbidity in adult asthmatics. Little is known about the effect of AR/AC
      and other factors on mortality among adult asthmatics. The aim was to study
      mortality and its risk factors in adults with and without asthma. METHODS: We
      randomly selected 1648 asthmatics with age over 30 years from national registers
      and matched the asthma sample with one or two controls. Baseline information was
      obtained by a questionnaire in 1997, and the study population was linked with the
      death certificate information of Statistics Finland from 1997 to 2013. Overall
      and cause-specific survival between the groups was compared in several adjusted
      models. RESULTS: During a mean follow-up period of 15.6 years, 221 deaths among
      1052 asthma patients and 335 deaths among 1889 nonasthmatics were observed.
      Cardiovascular diseases were the main cause of death in both groups. Asthma was
      associated with increased all-cause mortality (adjusted HR 1.25; 95% CI 1.05
      1.49, P = .011) as well as mortality from chronic obstructive pulmonary disease
      (HR 12.0, 4.18-34.2, P < .001) and malignant neoplasms of respiratory organs (HR
      2.33, 1.25-4.42, P = .008). Among asthmatics, smoking was associated with
      increased all-cause mortality, and self-reported AR/AC was associated with
      decreased mortality. Among nonasthmatics, smoking, and obesity were associated
      with increased all-cause mortality, whereas female gender showed an association
      with a decreased risk. CONCLUSIONS: Increased mortality among adult asthmatics
      was largely explained by the development of COPD, malignant respiratory tract
      neoplasms, and cardiovascular diseases. Smoking cessation is important for
      reduction in total mortality in both asthmatic and nonasthmatic adults. AR/AC was
      associated with decreased mortality only in asthmatics. Thus, studies in other
      populations of larger size are needed to explore further the nature of this
      association.

PMID- 29461633
TI  - Neuromuscular dysfunction in the cancer patient: Evaluation and treatment.
AB  - Cancer is a common diagnosis. In conjunction with various anti-neoplastic
      therapies delivered sequentially or concurrently, it makes oncology patients
      among the most complex to treat. This review uses a series of case studies to
      discuss the diagnosis and treatment of cancer-related nerve and muscle disorders.
      Oncologic treatment interventions such as surgery, chemotherapy, radiation
      therapy, and hormonal therapy, often have predictable side-effects, and sometimes
      their associated disability can be mitigated, especially if recognized early.
      Disease progression can mimic other diagnoses. The case studies provide a lens
      through which to study the presenting symptoms, differential diagnoses,
      diagnostic evaluation, and treatment interventions. These are all considered
      within the context of the patient's prognosis and health-related quality of life.
      Muscle Nerve 58: 335-343, 2018.

PMID- 29461634
TI  - Feasibility study of sucrose and fat replacement using inulin and rebaudioside A
      in cake formulations.
AB  - : Cake is a popular food around the world, however, it is considered as unhealthy
      due to its high fat and sucrose content. To satisfy customers' demand for a low
      fat and sucrose cake, in this research both sucrose and fat content of the cake
      were reduced by using rebaudioside A (Reb A; as a natural sucrose replacer) and
      inulin (as a natural fat replacer) at 0%, 25%, 50%, 75%, and 100%. The water
      content of different formulation was adjusted to obtain a constant batter
      viscosity similar to the control (3,757 cP). By reducing sucrose and fat content
      up to 50%, water activity increased and the cakes became more asymmetrical.
      However, other physical properties including baking weight loss, height, volume,
      crust color, and texture were similar to those of the control. Higher levels of
      replacement (75% and 100%) resulted in remarkable loss of different quality
      attributes. These samples showed higher water activity and baking loss, lower
      volume, harder texture, darker color, and highly asymmetrical shape. Thus,
      successful reduction of both fat and sucrose in cakes is possible by using inulin
      and Reb A at replacement levels no more than 50%. PRACTICAL APPLICATIONS:
      Customers' demand for healthy and yet tasty and high-quality foods is increasing
      around the world. Therefore, finding applicable and safe methods to produce such
      products is of great interest in the food manufacturing to satisfy customers.
      Health conscious customers avoid consumption of cakes because it contains high
      sucrose and fat content. Many studies have been performed to reduce either fat or
      sucrose content, while a few studies are available to show the reduction of both
      fat and sucrose in the same product. This study indicates the results of an
      applicable method to reduce fat and sucrose content of cakes simultaneously.
      Using rebaudioside A (as a natural sucrose replacer) and inulin (as a natural fat
      replacer) up to 50% of sucrose and fat content of cakes were reduced and the
      resulting cake had very similar physical properties to the control.

PMID- 29461636
TI  - Dental knowledge and dental service utilization: A 2-year follow-up study.
AB  - OBJECTIVES: To investigate associations of dental knowledge with dental service
      utilization over 2 years in South Australians aged 45-54 years. METHODS: In 2004
      2005, a random sample of 2469 adults aged 45-54 years from Adelaide, South
      Australia, who were selected from the Australian electoral roll was surveyed. The
      outcome variables were the numbers of visits and dental services received over 2
      years. Data were analysed using log-binomial and Poisson regression. Statistical
      significance was determined at P < .05. RESULTS: The response rates were 43.8% in
      the study group (n = 879) and 50.7% in the comparison group (n = 107). Oral
      examinations were conducted on 709 persons (81% of study group participants).
      Dental services data were collected from approximately 60% of participants at the
      end of years 1 and 2. After adjusting for sex, education, health card status,
      toothbrushing and inadequate dentition, higher caries knowledge and periodontal
      knowledge scores were associated with higher percentages of persons making dental
      visits (prevalence ratio, 95% CI: 1.2, 1.1-1.3 and 1.1, 1.0-1.3), and lower rates
      of extraction (rate ratio, 95% CI: 0.2, 0.1-0.4 and 0.4, 0.3-0.7) and endodontic
      services (0.5, 0.3-0.9 and 0.5, 0.3-0.7). Higher caries knowledge was associated
      with lower rates of fillings (0.8, 0.7-0.9) and denture services (0.1, 0.0-0.6),
      while higher periodontal knowledge was associated with higher numbers of visits
      (1.3, 1.2-1.5), and prophylaxis services (1.4, 1.1-1.8) and crowns (1.7, 1.1
      2.5). CONCLUSION: South Australians aged 45-54 years with higher dental knowledge
      had lower rates of invasive treatment over 2 years. These findings warrant policy
      initiatives that highlight the importance of dental knowledge in improving oral
      health.

PMID- 29461635
TI  - Clinical and mutational spectrum of highly differentiated, paired box 3:forkhead
      box protein o1 fusion-negative rhabdomyosarcoma: A report from the Children's
      Oncology Group.
AB  - BACKGROUND: Pediatric paired box 3:forkhead box protein O1 fusion-negative (PF-)
      rhabdomyosarcoma (RMS) represents a diverse spectrum of tumors with marked
      differences in histology, myogenic differentiation, and clinical behavior.
      METHODS: This study sought to evaluate the clinical and mutational spectrum of 24
      pediatric PF- human RMS tumors with high levels of myogenic differentiation.
      Tumors were sequenced with OncoPanel v.2, a panel consisting of the coding
      regions of 504 genes previously linked to human cancer. RESULTS: Most of the
      tumors (19 of 24) arose at head/neck or genitourinary sites, and the overall
      survival rate was 100% with a median follow-up time of 4.6 years (range, 1.4-8.6
      years). RAS pathway gene mutations were the most common mutations in PF-, highly
      differentiated RMS tumors. In addition, Hedgehog (Hh) and mechanistic target of
      rapamycin (mTOR) gene mutations with evidence for functional relevance (high
      impact) were identified in subsets of tumors. The presence of Hh and mTOR pathway
      gene mutations was mutually exclusive and was associated with high-impact RAS
      pathway gene mutations in 3 of 4 Hh-mutated tumors and in 1 of 6 mTOR-mutated
      tumors. CONCLUSIONS: Interestingly, Hh and mTOR gene mutations were previously
      associated with rhabdomyomas, which are also known to preferentially arise at
      head/neck and genitourinary sites. Findings from this study further support the
      idea that PF-, highly differentiated RMS tumors and rhabdomyomas may represent a
      continuous spectrum of tumors. Cancer 2018;124:1973-81. (c) 2018 American Cancer
      Society.

PMID- 29461637
TI  - PREDICTORS OF SELF-REPORTED GAINS IN A RELATIONSHIP-BASED HOME-VISITING PROJECT
      FOR MOTHERS AFTER CHILDBIRTH.
AB  - We assessed mothers' self-reported gains from a postpartum home-visiting (HV)
      project in which home visitors are volunteer mothers from the community.
      Hypotheses were that gains are positively related to (a) mothers' felt-closeness
      with their home visitor, (b) mothers' level of sociodemographic risk, and (c) the
      home visitors' preproject training in support services for families or children
      (Professionalism). One hundred sixty-four clients returned written evaluations of
      the HV project. Items assessing gains were reduced to two factors: Improved Well
      Being ("Self") and Improved Infant Care ("Infant"). Repeated measures general
      linear models, with Gains (Self, Infant) as the repeated measure, and multiple
      regression analyses evaluated the hypotheses. Across the sample, gains on both
      factors were moderate, although gain scores were higher regarding Self than for
      Infant. Results show that (a) Mothers' felt-closeness with their volunteer was
      strongly related to mothers' gains; (b) high-risk mothers gained more from the
      project than did mothers of lower risk, particularly regarding Infant Care; and
      (c) mothers visited by volunteers who were professionals reported more
      substantial gains than did mothers visited by volunteers who were not
      professionals. Findings can help explain variance in mothers' gains from such
      projects and could be useful in improving their efficacy.

PMID- 29461638
TI  - Dynamic changes in display architecture and function across environments revealed
      by a systems approach to animal communication.
AB  - Animal communication is often structurally complex and dynamic, with signaler and
      receiver behavior varying in response to multiple environmental factors. To date,
      studies assessing signal dynamics have mostly focused on the relationships
      between select signaling traits and receiver responses in a single environment.
      We use the wolf spider Schizocosa floridana to explore the relationships between
      courtship display form and function across two social contexts (female presence
      vs absence) and two light environments (light vs dark). We use traditional
      analytical methods to determine predictors of copulation success (i.e., signal
      function) and examine these predictors in a structural context by overlaying them
      on signal phenotype networks (Wilkins et al. 2015). This allows us to explore
      system design principles (degeneracy, redundancy, pluripotentiality), providing
      insight into hypotheses regarding complex signal evolution. We found that both
      social context and light environment affect courtship structure, although the
      predictors of mating success remain similar across light environments, suggesting
      system degeneracy. Contrastingly, the same display traits may serve different
      functions across social environments, suggesting pluripotentiality. Ultimately,
      our network approach uncovers a complexity in display structure and function that
      is missed by functional analyses alone, highlighting the importance of systems
      based methodologies for understanding the dynamic nature of complex signals.

PMID- 29461639
TI  - Impact of the affordability of novel agents in patients with multiple myeloma:
      Real-world data of current clinical practice in Mexico.
AB  - BACKGROUND: The treatment of multiple myeloma (MM) has become costly and
      difficult to access for patients living in low-income to middle-income countries.
      METHODS: The current retrospective study included 148 patients in Mexico with
      newly diagnosed MM, and was performed to compare the outcomes of patients with
      and without access to novel agents. The records of 77 patients admitted to a
      public hospital (PubC) and 71 patients cared for within private health systems
      (PrivC) from November 2007 to July 2016 were reviewed. RESULTS: Compared with
      those treated in PrivC, patients receiving care at PubC were more likely to be
      diagnosed with advanced disease. A thalidomide-based regimen was the most common
      induction treatment used at PubC, whereas a bortezomib-based regimen was used
      most often in PrivC. The median follow-up was 41 months. Patients in PrivC
      demonstrated better response rates and survival; 65% of patients treated in PrivC
      versus 41% treated at PubC achieved a very good partial response or better (P =
      .005). The median progression-free survival and median overall survival were 23
      months and 51 months, respectively, for patients treated at PubC and 41 months
      and 79 months, respectively, for those treated in PrivC (P<.001). More patients
      underwent autologous stem cell transplantation in PrivC. When adjustments were
      made for covariates, patients treated at PubC experienced a higher risk of death
      compared with patients receiving care in PrivC (hazard ratio, 2.0; 95% confidence
      interval, 1.0-4.3 [P = .04]). CONCLUSIONS: Stage at diagnosis, induction regimen,
      and autologous stem cell transplantation were found to be contributors to
      survival disparities between patients with MM treated at PubC compared with PrivC
      in Mexico. These findings underscore the need to improve access to novel agents
      and stem cell transplantation in public health systems. Cancer 2018;124:1946-53.
      (c) 2018 American Cancer Society.

PMID- 29461640
TI  - Rapid evaluation of the texture properties of melon (Cucumis melo L. Var.
      reticulata cv. Green net) using near infrared spectroscopy.
AB  - : The near infrared (NIR) spectroscopy as the rapid nondestructive method was
      aimed to be applied for determination of the texture properties of melon intact
      fruit and pulp including initial firmness, rupture force, average firmness,
      rupture distance, toughness, average penetrating force and penetrating energy.
      The data from the reference method of texture analyzer were correlated with the
      NIR spectral data. The result showed that, only the two properties including
      rupture force and penetrating force in pulp could be predicted by NIR
      spectroscopy technique. The determination coefficient of validation (r2 ) for
      prediction of rupture force and penetrating force in the pulp of melon using
      intact fruit spectra were 0.850 and 0.845, respectively. The r2 , for prediction
      of rupture force and penetrating force in the pulp of melon using pulp spectra
      were 0.813 and 0.778, respectively. This indicated that the NIR spectroscopy
      protocol developed here was useful for research works such as breeding and
      postharvest research, the melon processing factory and also the import and export
      of melon. PRACTICAL APPLICATIONS: The near infrared spectroscopy protocol
      developed for determination of rupture force and penetrating force in pulp using
      intact fruit spectra as a nondestructive method will be useful for research works
      such as breeding and postharvest research, the melon processing factory and also
      the import and export of melon. There are also the protocol developed using pulp
      spectra can be used for texture determination of fresh-cut melon.

PMID- 29461641
TI  - Mutational studies of the Aux/IAA proteins in Physcomitrella reveal novel
      insights into their function.
AB  - The plant hormone auxin regulates many aspects of plant growth and development.
      Auxin signaling involves hormone perception by the TRANSPORT INHIBITOR
      RESPONSE/AUXIN F-BOX (TIR1/AFB)-Aux/IAA co-receptor system, and the subsequent
      degradation of the Aux/IAA transcriptional repressors by the ubiquitin proteasome
      pathway. This leads to the activation of downstream gene expression and diverse
      physiological responses. Here, we investigate how the structural elements in the
      Aux/IAAs determine their function in Auxin perception and transcriptional
      repression. We took advantage of the facile genetics of the moss Physcomitrella
      patens to determine the activity of wild-type and mutant PpIAA1a proteins in a
      Deltaaux/iaa null background. In this way, Aux/IAA function was characterized at
      the molecular and physiological levels without the interference of genetic
      redundancy. We identified and characterized degron variants in Aux/IAAs that
      affect their stability and Auxin response. We also demonstrated that neither the
      Aux/IAA EAR motif nor Aux/IAA oligomerization is essential for the repressive
      function of Aux/IAA. Our study demonstrates how key elements within the Aux/IAA
      proteins fine tune stability and repressor activity, as well as the long-term
      developmental outcome.

PMID- 29461642
TI  - Brachial plexitis or neuritis? MRI features of lesion distribution in Parsonage
      Turner syndrome.
AB  - INTRODUCTION: This study seeks to characterize lesion distribution in Parsonage
      Turner Syndrome (PTS) using high-resolution MRI. METHODS: MRIs of 27 patients
      with clinically confirmed PTS were reviewed. Two radiologists independently
      evaluated the brachial plexus proper, side and terminal plexus branches, and more
      distal, upper extremity nerves. RESULTS: All patients had at least 1 clinically
      involved nerve. MRI revealed that the plexus appeared normal in 24 of 27
      patients; in 3 other patients, signal hyperintensity was seen immediately
      proximal to the take-off of abnormal side or terminal branch nerves. Focal
      intrinsic constrictions were detected in 32 of 38 nerves. MRI interobserver
      agreement was high (Cohen's kappa = 0.839). DISCUSSION: MRI findings,
      corroborated by electrodiagnostic testing, localized abnormalities to plexus
      branches and peripheral nerves, suggesting that PTS is characterized by 1 or more
      mononeuropathies rather than changes involving a portion of or the complete
      plexus proper. These results may improve diagnosis, prognostication, and
      management. Muscle Nerve 58: 359-366, 2018.

PMID- 29461644
TI  - RasGRP3, a Ras guanyl releasing protein 3 that contributes to malignant
      proliferation and aggressiveness in human esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers
      worldwide; however, clinical and pathological parameters have limited ability in
      discriminating between clinically significant and indolent ESCC. Since RasGRP3
      transcript levels have prognostic value in discriminating ESCC with different
      clinical aggressiveness, we decided to investigate its putative oncogenic role in
      ESCC. We found that RasGRP3 was highly expressed in ESCC cells. Suppression of
      endogenous RasGRP3 expression in esophageal cell lines reduced Ras-GTP formation
      as well as AKT phosphorylation. RasGRP3 suppression also inhibited cell invasion
      and migration and reduced proliferation, demonstrating the importance of RasGRP3
      for the transformed phenotype of melanoma cells. Suppression of RasGRP3
      expression in these cells inhibited downstream RasGRP3 responses and suppressed
      cell growth and migration, confirming the functional role of RasGRP3 in the
      altered behaviour of these cells. This suggests that RasGRP3 may function as a
      Ras activator in the phosphoinositide signalling pathway and may potentially
      serve as a new therapeutic target.

PMID- 29461643
TI  - Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia.
AB  - OBJECTIVE: Focal cortical dysplasias (FCDs) are an important cause of drug
      resistant epilepsy. In this work, we aimed to investigate whether abnormal gene
      regulation, mediated by microRNA, could be involved in FCD type II. METHODS: We
      used total RNA from the brain tissue of 16 patients with FCD type II and 28
      controls. MicroRNA expression was initially assessed by microarray. Quantitative
      polymerase chain reaction, in situ hybridization, luciferase reporter assays, and
      deep sequencing for genes in the mTOR pathway were performed to validate and
      further explore our initial study. RESULTS: hsa-let-7f (p = 0.039), hsa-miR-31 (p
      = 0.0078), and hsa-miR34a (p = 0.021) were downregulated in FCD type II, whereas
      a transcription factor involved in neuronal and glial fate specification, NEUROG2
      (p < 0.05), was upregulated. We also found that the RND2 gene, a NEUROG2-target,
      is upregulated (p < 0.001). In vitro experiments showed that hsa-miR-34a
      downregulates NEUROG2 by binding to its 5'-untranslated region. Moreover, we
      observed strong nuclear expression of NEUROG2 in balloon cells and dysmorphic
      neurons and found that 28.5% of our patients presented brain somatic mutations in
      genes of the mTOR pathway. INTERPRETATION: Our findings suggest a new molecular
      mechanism, in which NEUROG2 has a pivotal and central role in the pathogenesis of
      FCD type II. In this way, we found that the downregulation of hsa-miR-34a leads
      to upregulation of NEUROG2, and consequently to overexpression of the RND2 gene.
      These findings indicate that a faulty coupling in neuronal differentiation and
      migration mechanisms may explain the presence of aberrant cells and complete
      dyslamination in FCD type II. Ann Neurol 2018;83:623-635.

PMID- 29461645
TI  - Enzymatic or In Vivo Installation of Propargyl Groups in Combination with Click
      Chemistry for the Enrichment and Detection of Methyltransferase Target Sites in
      RNA.
AB  - m6 A is the most abundant internal modification in eukaryotic mRNA. It is
      introduced by METTL3-METTL14 and tunes mRNA metabolism, impacting cell
      differentiation and development. Precise transcriptome-wide assignment of m6 A
      sites is of utmost importance. However, m6 A does not interfere with Watson-Crick
      base pairing, making polymerase-based detection challenging. We developed a
      chemical biology approach for the precise mapping of methyltransferase (MTase)
      target sites based on the introduction of a bioorthogonal propargyl group in
      vitro and in cells. We show that propargyl groups can be introduced enzymatically
      by wild-type METTL3-METTL14. Reverse transcription terminated up to 65 % at m6 A
      sites after bioconjugation and purification, hence enabling detection of METTL3
      METTL14 target sites by next generation sequencing. Importantly, we implemented
      metabolic propargyl labeling of RNA MTase target sites in vivo based on propargyl
      l-selenohomocysteine and validated different types of known rRNA methylation
      sites.

PMID- 29461646
TI  - Younger age and in situ duration of peripheral intravenous catheters were risk
      factors for extravasation in a retrospective paediatric study.
AB  - AIM: Epidemiological data on the incidence and risk factors of extravasation of
      peripheral intravenous catheters (PIVC) in neonates and children are scarce and
      that is what this study explored. METHODS: This was a one-year retrospective
      study of all neonates and paediatric intensive care patients with at least one
      recorded PIVC at the Geneva University Hospitals, Switzerland, in 2013. The
      extravasation rate was determined for all patients, including neonates below 28
      days, and for all PIVCs. Multivariate analysis of the associated risk factors was
      performed. RESULTS: We analysed 1300 PIVC in 695 paediatric patients with a
      median age of 1.5 years. The overall extravasation incidence was 17.6% for all
      patients and 11.7% for PIVC. The overall incidence rate of PIVC extravasation was
      4.5 per 100 catheters days, and the risk was highest in the 201 neonates, at
      28.4%. The incidence rate four days after insertion of the PIVC was around three
      times higher than on day one. Neonates and the in situ duration of PIVCs were
      associated risk factors (p < 0.001). CONCLUSION: Extravasation was frequent and
      neonates were particularly at risk. Younger age and longer in situ PIVC duration
      were independent risk factors for extravasation.

PMID- 29461647
TI  - Comparison of three dehydration scales showed that they were of limited or no
      value for assessing small children with acute diarrhoea.
AB  - AIM: We explored the diagnostic accuracy of the clinical dehydration scale (CDS),
      the World Health Organization (WHO) scale and the Gorelick scale for assessing
      dehydration in children admitted to a Tanzanian referral hospital. METHODS: This
      was a prospective, observational study, carried out from April 2015 to January
      2017 on children aged one month to five years admitted to the hospital with acute
      diarrhoea lasting less than five days. Before rehydration therapy, each patient's
      weight was recorded and the degree of dehydration was assessed based on the three
      scales. The reference standard was the percentage weight change between admission
      and discharge. The main outcomes were the sensitivity, specificity and positive
      and negative likelihood ratios (LRs) of the scales. RESULTS: Data from 124
      eligible patients were available. The CDS showed limited value for ruling in
      cases with some dehydration (LR 1.9, 95% confidence interval 1.1-2.8), but was of
      no value in assessing no and moderate to severe dehydration. The WHO and Gorelick
      scales were of no value in evaluating any degree of dehydration. CONCLUSION: The
      WHO and Gorelick dehydration scales were no use for assessing dehydration in
      small children, and the CDS was of limited use for predicting cases with some
      dehydration.

PMID- 29461648
TI  - Unprecedented Dearomatized Spirocyclopropane in a Sequential Rhodium(III)
      Catalyzed C-H Activation and Rearrangement Reaction.
AB  - An unprecedented dearomatized spirocyclopropane intermediate was discovered in a
      sequential Cp*RhIII -catalyzed C-H activation and Wagner-Meerwein-type
      rearrangement reaction. How the oxidative O-N bond is cleaved and the role of
      HOAc were uncovered in this study. Furthermore, a Cp*RhIII -catalyzed
      dearomatization reaction of N-(naphthalen-1-yloxy)acetamide with strained olefins
      was developed, affording a variety of spirocyclopropanes.

PMID- 29461649
TI  - Contextual and stress process factors associated with head and neck cancer
      caregivers' physical and psychological well-being.
AB  - Head and neck cancer (HNC) caregivers are especially vulnerable to poor outcomes
      because the HNC patients are at high risk for physical and functional
      impairments. This study examines contextual and stress process variables
      potentially associated with HNC caregivers' physical and psychological well
      being. Patient-caregiver variables included socio-demographics, primary stressors
      (caregiving, patient clinical characteristics, HNC-related symptoms/dysfunction),
      secondary stressors (caregiver employment, childcare responsibilities and sleep
      duration <7 hr), appraisal, and response (physical activity). General linear
      models modeled caregiver well-being, along with depression and anxiety. A total
      of 33 patient-caregiver dyads were included. Most caregivers were female (81.8%)
      and patient spouses/partners (72.7%). Factors significantly associated with
      better caregiver physical well-being included caregiver older age, <2
      comorbidities, >=7 hr of sleep, >=3 days/week physical activity, and patient
      swallowing and speech dysfunction. Factors significantly associated with better
      caregiver mental health functioning were less patient social dysfunction and less
      perceived caregiving burden. Short nighttime sleep, higher caregiver burden, and
      <3 days/week physical activity were also significantly related to caregivers'
      depression and anxiety. Results suggested caregiver behaviors and perceived
      burden, along with patient HNC concerns are linked with caregiver well-being.
      These behavioral, cognitive, and patient factors should be incorporated into
      caregiver screening tools or targeted with behavioral interventions to improve
      caregiver well-being.

PMID- 29461651
TI  - Children living in the slums of Bangladesh face risks from unsafe food and water
      and stunted growth is common.
AB  - AIM: This study investigated the microbial quality of food and water consumed by
      children in four slums in Dhaka, the capital of Bangladesh, together with the
      associated risk factors. METHODS: This cross-sectional study took place from
      December 2015 to May 2016 and focused on 360 children under the age of five. We
      recorded household food security, namely adequate food for a healthy life, socio
      economic and nutritional status, hygiene and feeding practices. Food and water
      samples were analysed. RESULTS: We found that 63% of the children were
      malnourished and 58% were stunted. Yeast and moulds were detected in 86% of the
      food samples and coliforms in 73%. All the water samples were contaminated with
      faecal coliforms, yeasts and moulds and Staphylococcus. Food insecurity affected
      83% of households. Children were twice as likely to be malnourished if they were
      born with a perceived low birthweight or their mothers did not wash their hands
      with soap after cleaning the child's bottom following defecation. Exclusively
      breastfed children were less likely to develop malnutrition. CONCLUSION: Children
      from the Dhaka slums were frequently stunted and malnourished and contaminated
      food and water was common. Integrated efforts are essential to create public
      awareness about hygiene.

PMID- 29461652
TI  - The impact of sexual orientation on body image, self-esteem, urinary and sexual
      functions in the experience of prostate cancer.
AB  - Prostate cancer (PCa) poses a large health burden globally. Research indicates
      that men experience a range of psychological challenges associated with PCa
      including changes to identity, self-esteem and body image. The ways in which
      sexual orientation plays a role in the experience of PCa, and the subsequent
      impact on quality of life (QoL), body image and self-esteem have only recently
      been addressed. By addressing treatment modality, where participant numbers were
      sufficient, we also sought to explore whether gay (homosexual) men diagnosed with
      PCa (PCaDx) and with a primary treatment modality of surgery would report
      differences in body image and self-esteem compared with straight (heterosexual)
      men with PCaDx with a primary treatment modality of surgery, compared with gay
      and straight men without PCaDx. The results of our study identified overall
      differences with respect to PCaDx (related to urinary function, sexual function
      and health evaluation), and sexual orientation (related to self-esteem), rather
      than interactions between sexual orientation and PCaDx. Gay men with PCaDx
      exhibited higher levels of urinary functioning than straight men with PCaDx, the
      difference being reversed for gay and straight men without PCaDx; but this result
      narrowly failed to achieve statistical significance, suggesting a need for
      further research, with larger samples.

PMID- 29461650
TI  - Sex matters: females in proestrus show greater diazepam anxiolysis and brain
      derived neurotrophin factor- and parvalbumin-positive neurons than males.
AB  - In humans and animal models, sex differences are reported for anxiety-like
      behavior and response to anxiogenic stimuli. In the current work, we studied
      anxiety-like behavior and response to the prototypical anti-anxiety drug,
      diazepam. We used 6th generation outbred lines of adult Long Evans rats with high
      and low anxiety-like behavior phenotypes to investigate the impact of proestrus
      on the baseline and diazepam-induced behavior. At three doses of diazepam (0,
      0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus
      maze of adult male and female rats. We assessed parvalbumin and brain-derived
      neurotrophin protein levels in forebrain and limbic structures implicated in
      anxiety/stress using immunohistochemistry. At baseline, we saw significant
      differences between anxiety lines, with high anxiety lines displaying less time
      on the open arms of the elevated plus maze, and less open arm entries, regardless
      of sex. During proestrus, high anxiety females showed less anxiety-like behavior
      at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at
      0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was
      elevated in females in the medial prefrontal cortex and central amygdala, while
      parvalbumin-immunoreactive cells were greater in males in the medial prefrontal
      cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and
      dentate gyrus relative to males from the same line. In sum, when tested in
      proestrus, females showed greater anxiolytic effects of diazepam relative to
      males, and this correlated with increases in neurotrophin and parvalbumin neuron
      density in corticolimbic structures.

PMID- 29461653
TI  - Epigenetic marks of in utero exposure to gestational diabetes and childhood
      adiposity outcomes: the EPOCH study.
AB  - AIMS: To identify gestational diabetes mellitus exposure-associated DNA
      methylation changes and assess whether such changes are also associated with
      adiposity-related outcomes. METHODS: We performed an epigenome-wide association
      analysis, using Illumina 450k methylation arrays, on whole blood collected, on
      average, at 10.5 years of age from 81 gestational diabetes-exposed and 81
      unexposed offspring enrolled in the EPOCH (Exploring Perinatal Outcomes in
      Children) study, and on the cord blood of 31 gestational diabetes-exposed and 64
      unexposed offspring enrolled in the Colorado Healthy Start cohort. Validation was
      performed by pyrosequencing. RESULTS: We identified 98 differentially methylated
      positions associated with gestational diabetes exposure at a false discovery rate
      of <10% in peripheral blood, with 51 loci remaining significant (plus additional
      40 loci) after adjustment for cell proportions. We also identified 2195
      differentially methylation regions at a false discovery rate of <5% after
      adjustment for cell proportions. We prioritized loci for pyrosequencing
      validation and association analysis with adiposity-related outcomes based on
      strengths of association and effect size, network and pathway analysis, analysis
      of cord blood, and previous publications. Methylation in six out of nine (67%)
      gestational diabetes-associated genes was validated and we also showed that
      methylation of SH3PXD2A was significantly (P<0.05) associated with multiple
      adiposity-related outcomes. CONCLUSIONS: Our findings suggest that epigenetic
      marks may provide an important link between in utero exposure to gestational
      diabetes and obesity in childhood, and add to the growing body of evidence that
      DNA methylation is affected by gestational diabetes exposure.

PMID- 29461654
TI  - Acute responses to structured aerobic and resistance exercise in women with
      gestational diabetes mellitus.
AB  - Research on the acute responses to exercise in pregnancy is scarce, especially
      for women affected by gestational diabetes mellitus (GDM). The aim of this study
      was to investigate responses to a single bout of exercise performed multiple
      times throughout the pregnancy in women diagnosed with GDM. Data from 18 pregnant
      women (aged: 32.8 +/- 3.8) diagnosed with GDM, treated with diet only, were
      analyzed. Participants' pre-pregnancy body mass index was 24.4 +/- 4.9 kg/m2 ,
      50% of them were nulliparous, and 50% of the sample regularly exercised before
      the pregnancy. The exercise intervention consisted of an individual structured
      aerobic and resistance exercise program performed twice per week from the time of
      diagnosis until at least the 36th week of pregnancy. The exercise program
      included 20 minutes of aerobic exercise, 20-25 minutes of resistance exercise,
      and 10 minutes of cool down. Maternal heart rate, systolic and diastolic blood
      pressure, temperature and fetal heart rate were measured at every exercise
      session, along with blood glucose on 3 occasions. In total, 365 exercise sessions
      were analyzed (85 in the second trimester and 280 in the third trimester), on
      average 20.3 +/- 7.7 per participant. Heart rate and fetal heart rate were
      elevated during both the aerobic and resistance parts of the exercise session (P
      < .01) in comparison with the baseline while systolic and diastolic blood
      pressure did not change in the total sample. There was a slight elevation in
      tympanic membrane temperature during the aerobic part of the session (P < .01).
      All parameters returned to baseline levels by the end of the session. Glucose
      levels dropped from the baseline, from 4.7 +/- 0.6 to 3.9 +/- 0.4 mmol/L (P <
      .01). There were no differences in responses to exercise between the second and
      third trimesters, nor between pre-pregnancy exercisers and non-exercisers. The
      combination of aerobic and resistance exercise for women diagnosed with GDM does
      not have harmful short-term effects if performed according to guidelines.
      Likewise, exercise can be considered useful for controlling hyperglycemia in
      pregnancy for women affected by GDM.

PMID- 29461656
TI  - Identification and characterization of acetyltransferase-type toxin-antitoxin
      locus in Klebsiella pneumoniae.
AB  - A type II toxin-antitoxin (TA) system, in which the toxin contains a Gcn5-related
      N-acetyltransferase (GNAT) domain, has been characterized recently. GNAT toxin
      acetylates aminoacyl-tRNA and blocks protein translation. It is abolished by the
      cognate antitoxin that contains the ribbon-helix-helix (RHH) domain. Here, we
      present an experimental demonstration of the interaction of the GNAT-RHH complex
      with TA promoter DNA. First, the GNAT-RHH TA locus kacAT was found in Klebsiella
      pneumoniae HS11286, a strain resistant to multiple antibiotics. Overexpression of
      KacT halted cell growth and resulted in persister cell formation. The crystal
      structure also indicated that KacT is a typical acetyltransferase toxin. Co
      expression of KacA neutralized KacT toxicity. Expression of the bicistronic kacAT
      locus was up-regulated during antibiotic stress. Finally, KacT and KacA formed a
      heterohexamer that interacted with promoter DNA, resulting in negative
      autoregulation of kacAT transcription. The N-terminus region of KacA accounted
      for specific binding to the palindromic sequence on the operator DNA, whereas its
      C-terminus region was essential for the inactivation of the GNAT toxin. These
      results provide an important insight into the regulation of the GNAT-RHH family
      TA system.

PMID- 29461655
TI  - Exploring the rationale for combining ionizing radiation and immune checkpoint
      blockade in head and neck cancer.
AB  - BACKGROUND: The ability of radiation to enhance antitumor immunity under specific
      experimental conditions is well established. Here, we explore preclinical data
      and the rationale for combining different radiation doses and fractions with
      immune checkpoint blockade immunotherapy. METHODS: We conducted a review of the
      literature. RESULTS: The ability of high-dose or hypofractionated radiation to
      enhance antitumor immunity resulting in additive or synergistic tumor control
      when combined with checkpoint blockade is well studied. Whether low-dose daily
      fractionated radiation does the same is less well studied and available data
      suggests it may be immunosuppressive. CONCLUSION: Although daily fractionated
      radiation is well established as the standard of care for the treatment of
      patients with head and neck cancer, how this radiation schema alters antitumor
      immunity needs further study. If the radiation doses and fractions alter
      antitumor immunity differently can have profound implications in the rational
      design of clinical trials investigating whether radiation can enhance response
      rates to immune checkpoint blockade.

PMID- 29461657
TI  - Vestibular modulation of peripersonal space boundaries.
AB  - Human-environment interactions are mediated through the body and occur within the
      peripersonal space (PPS), the space immediately adjacent to and surrounding the
      body. The PPS is taken to be a critical interface between the body and the
      environment, and indeed, body-part specific PPS remapping has been shown to
      depend on body-part utilization, such as upper limb movements in otherwise static
      observers. How vestibular signals induced by whole-body movement contribute to
      PPS representation is less well understood. In a series of experiments, we mapped
      the spatial extension of the PPS around the head while participants were
      submitted to passive whole-body rotations inducing vestibular stimulation. Forty
      six participants, in three experiments, executed a tactile detection reaction
      time task while task-irrelevant auditory stimuli approached them. The maximal
      distance at which the auditory stimulus facilitated tactile reaction time was
      taken as a proxy for the boundary of peri-head space. The present results
      indicate two distinct vestibular effects. First, vestibular stimulation speeded
      tactile detection indicating a vestibular facilitation of somatosensory
      processing. Second, vestibular stimulation modulated audio-tactile interaction of
      peri-head space in a rotation direction-specific manner. Congruent but not
      incongruent audio-vestibular motion stimuli expanded the PPS boundary further
      away from the body as compared to no rotation. These results show that vestibular
      inputs dynamically update the multisensory delineation of PPS and far space,
      which may serve to maintain accurate tracking of objects close to the body and to
      update spatial self-representations.

PMID- 29461658
TI  - One-Pot Tandem Photoredox and Cross-Coupling Catalysis with a Single Palladium
      Carbodicarbene Complex.
AB  - The combination of conventional transition-metal-catalyzed coupling (2 e-
      process) and photoredox catalysis (1 e- process) has emerged as a powerful
      approach to catalyze difficult cross-coupling reactions under mild reaction
      conditions. Reported is a palladium carbodicarbene (CDC) complex that mediates
      both a Suzuki-Miyaura coupling and photoredox catalysis for C-N bond formation
      upon visible-light irradiation. These two catalytic pathways can be combined to
      promote both conventional transition-metal-catalyzed coupling and photoredox
      catalysis to mediate C-H arylation under ambient conditions with a single
      catalyst in an efficient one-pot process.

PMID- 29461659
TI  - Live Imaging of Type I Collagen Assembly Dynamics in Osteoblasts Stably
      Expressing GFP and mCherry-Tagged Collagen Constructs.
AB  - Type I collagen is the most abundant extracellular matrix protein in bone and
      other connective tissues and plays key roles in normal and pathological bone
      formation as well as in connective tissue disorders and fibrosis. Although much
      is known about the collagen biosynthetic pathway and its regulatory steps, the
      mechanisms by which it is assembled extracellularly are less clear. We have
      generated GFPtpz and mCherry-tagged collagen fusion constructs for live imaging
      of type I collagen assembly by replacing the alpha2(I)-procollagen N-terminal
      propeptide with GFPtpz or mCherry. These novel imaging probes were stably
      transfected into MLO-A5 osteoblast-like cells and fibronectin-null mouse
      embryonic fibroblasts (FN-null-MEFs) and used for imaging type I collagen
      assembly dynamics and its dependence on fibronectin. Both fusion proteins co
      precipitated with alpha1(I)-collagen and remained intracellular without ascorbate
      but were assembled into alpha1(I) collagen-containing extracellular fibrils in
      the presence of ascorbate. Immunogold-EM confirmed their ultrastuctural
      localization in banded collagen fibrils. Live cell imaging in stably transfected
      MLO-A5 cells revealed the highly dynamic nature of collagen assembly and showed
      that during assembly the fibril networks are continually stretched and contracted
      due to the underlying cell motion. We also observed that cell-generated forces
      can physically reshape the collagen fibrils. Using co-cultures of mCherry- and
      GFPtpz-collagen expressing cells, we show that multiple cells contribute collagen
      to form collagen fiber bundles. Immuno-EM further showed that individual collagen
      fibrils can receive contributions of collagen from more than one cell. Live cell
      imaging in FN-null-MEFs expressing GFPtpz-collagen showed that collagen assembly
      was both dependent upon and dynamically integrated with fibronectin assembly.
      These GFP-collagen fusion constructs provide a powerful tool for imaging collagen
      in living cells and have revealed novel and fundamental insights into the dynamic
      mechanisms for the extracellular assembly of collagen. (c) 2018 American Society
      for Bone and Mineral Research.

PMID- 29461660
TI  - Outcomes at 7 years post-transplant in black vs nonblack kidney transplant
      recipients administered belatacept or cyclosporine in BENEFIT and BENEFIT-EXT.
AB  - Clinical outcomes are generally worse for black vs nonblack renal allograft
      recipients. In BENEFIT and BENEFIT-EXT, recipients were randomized to belatacept
      more intense-based, belatacept less intense-based, or cyclosporine-based
      immunosuppression. At year 7, belatacept was associated with superior graft
      survival vs cyclosporine in BENEFIT (recipients of living or standard criteria
      deceased donor kidneys); belatacept was associated with similar graft survival vs
      cyclosporine in BENEFIT-EXT (recipients of extended criteria donor kidneys). In
      both studies, renal function was superior for belatacept-treated vs cyclosporine
      treated patients. Seven-year outcomes were examined by race post hoc in each
      study. The effect of race and treatment on time to death or graft loss was
      compared using Cox regression. The interaction between treatment and race was
      also considered. Glomerular filtration rate (GFR) was estimated from months 1 to
      84 using a repeated-measures model. In total, 8.3% (55/666) and 13.1% (71/543) of
      patients in BENEFIT and BENEFIT-EXT, respectively, were black. Time to death or
      graft loss was similar in blacks and nonblacks. For both subgroups, estimated
      mean GFR increased over 7 years for belatacept, but declined for cyclosporine.
      Outcomes were similar in belatacept-treated black and nonblack patients. Due to
      the small number of black patients, these results must be interpreted with
      caution.

PMID- 29461661
TI  - Preoperative imaging for parathyroid localization in patients with concurrent
      thyroid disease: A systematic review.
AB  - BACKGROUND: Thyroid disease occurs more frequently in patients with
      hyperparathyroidism than the general population and hinders parathyroid
      localization. Identifying thyroid pathology before operating improves management
      and avoids the risks of reoperation in the neck. This review assesses imaging
      studies in patients with hyperparathyroidism and thyroid pathology to identify
      the ideal imaging methodology for patients with multigland disease. METHODS:
      Systematic review of original articles reporting sensitivity or positive
      predictive value (PPV) for one or more imaging modalities in patients with
      hyperparathyroidism and thyroid disease. RESULTS: Twenty-eight studies, 13
      prospective and 15 retrospective, met inclusion criteria. Nine modalities were
      evaluated, including: cervical ultrasound (n = 18), dual-phase 99m Tc-sestamibi
      (n = 14), subtraction scintigraphy (n = 11), combined ultrasound and scintigraphy
      (n = 8), single photon emission CT (SPECT; n = 5), SPECT-CT (n = 4), contrast
      enhanced ultrasound (n = 1), CT (n = 1), and MRI (n = 1). CONCLUSION: Combined
      ultrasound and scintigraphy is the most sensitive study to localize parathyroid
      adenomas in patients with hyperparathyroidism and thyroid disease, followed by
      hybrid SPECT-CT and SPECT.

PMID- 29461662
TI  - Lewis Acid Catalyzed Enantioselective Desymmetrization of Donor-Acceptor meso
      Diaminocyclopropanes.
AB  - The first Lewis acid catalyzed enantioselective ring-opening desymmetrization of
      a donor-acceptor meso-diaminocyclopropane is reported. The copper(II)-catalyzed
      Friedel-Crafts alkylation of indoles and one pyrrole with an unprecedented meso
      diaminocyclopropane delivered enantioenriched, diastereomerically pure urea
      products, which are structurally related to natural and synthetic bioactive
      compounds. The development of a new ligand through the investigation of an
      underexplored subclass of bis(oxazoline) ligands was essential for achieving high
      enantioselectivities.

PMID- 29461663
TI  - Ullazine Donor-pi bridge-Acceptor Organic Dyes for Dye-Sensitized Solar Cells.
AB  - A series of four ullazine-donor based donor-pi bridge-acceptor (D-pi-A) dyes have
      been synthesized and compared to a prior ullazine donor-acceptor (D-A) dye as
      well as a triphenylamine donor with an identical pi-bridge and acceptor. The D-pi
      A ullazine series demonstrates an unusually uniform-in-intensity panchromatic
      UV/Vis absorption spectrum throughout the visible region. This is in part due to
      the introduction of strong high-energy bands through incorporation of the
      ullazine building block as shown by computational analysis. The dyes were
      characterized on TiO2 films and in DSC devices. Performances of 5.6 % power
      conversion efficiency were obtained with IPCE onsets reaching 800 nm.

PMID- 29461664
TI  - Validation of the Chinese version of EORTC QLQ-BN20 for patients with brain
      cancer.
AB  - This is a single centre study in mainland China aiming to evaluate the
      reliability, validity and responsiveness of the Chinese version of EORTC QLQ
      BN20, designed by The European Organization for Research and Treatment of Cancer
      Quality of Life Group to evaluate the life quality of patients with brain tumour,
      cancer or metastases. One hundred and eighty-eight patients with primary or
      secondary brain cancer from Hunan Provincial Tumor Hospital during September 2013
      to June 2014 completed the Chinese EORTC QLQ-C30/BN20 questionnaires developed by
      translation, back translation and cultural adaptation. Results were statistically
      analysed using SPSS17.0. The internal consistency (Cronbach's alpha coefficient)
      was between .753 and .869, the correlation coefficients among items and its own
      dimension were bigger than .4, and all items had a better correlation with its
      own dimension. The Spearman was used to analyse the correlation of each dimension
      between EORTC QLQ-BN20 and EORTC QLQ-C30, and the result showed that individual
      dimensions were moderately correlated, other dimensions were weakly correlated.
      In conclusion, the Chinese version of EORTC QLQ BN20 questionnaire had great
      relevance, reliability, convergent validity and discriminant validity. It
      provides a valuable tool for the assessment of health-related quality of life in
      clinical studies of Chinese patients with primary or secondary brain cancer.

PMID- 29461665
TI  - Children with cow's milk allergy following an elimination diet had normal growth
      but relatively low plasma leptin at age two.
AB  - AIM: To assess nutrient intake, growth and nutritional status of infants with
      cow's milk allergy (CMA) who follow a therapeutic elimination diet since the
      first few months of life. METHODS: Sixty infants younger than four months of age
      with challenge-proven CMA and 60 healthy age-matched children were investigated.
      Anthropometric and body composition (BC) were assessed up to 24 months. Dietary
      intake was recorded by the parents for three consecutive days before visits at 6,
      12, 18 and 24 months. Blood albumin, prealbumin, retinol binding protein and
      metabolic-related hormones were examined at 24 months. RESULTS: The average age
      at enrolment was 2.9 +/- 1.0 months. At the end of the follow-up, there were no
      differences in daily milk consumption, nutrient intake, weight and height z
      scores or BC measures between the groups; however, the plasma leptin level was
      lower in infants with CMA (1.67 +/- 1.03 vs 2.05 +/- 1.48) (ng/mL) (p < 0.05)
      compared to healthy children. CONCLUSIONS: Children with CMA who followed an
      elimination diet could achieve a normal nutritional status, except for relatively
      lower plasma leptin levels, at the age of 2. Further studies with larger cohorts
      and research on the long-term consequences of these early differences are needed.

PMID- 29461666
TI  - Surgical management of the recurrent laryngeal nerve in thyroidectomy: American
      Head and Neck Society Consensus Statement.
AB  - "I have noticed in operations of this kind, which I have seen performed by others
      upon the living, and in a number of excisions, which I have myself performed on
      the dead body, that most of the difficulty in the separation of the tumor has
      occurred in the region of these ligaments.... This difficulty, I believe, to be a
      very frequent source of that accident, which so commonly occurs in removal of
      goiter, I mean division of the recurrent laryngeal nerve." Sir James Berry
      (1887).

PMID- 29461667
TI  - Computer vision detects subtle histological effects of dutasteride on benign
      prostate.
AB  - OBJECTIVE: To determine whether a computer vision-based approach applied to
      haematoxylin and eosin (H&E) prostate biopsy images can distinguish dutasteride
      treated tissue from placebo, and identify features associated with degree of
      responsiveness to 5alpha-reductase inhibitor (5ARI) therapy. SUBJECTS AND
      METHODS: Our study population comprised 100 treatment-adherent men without
      prostate cancer assigned to dutasteride or placebo in the REDUCE trial, who had
      slides available from mandatory year-4 biopsies. Half of the men also provided
      slides from a year-2 biopsy. We obtained 20* whole-slide images and used
      specialized software to generate a library of 1 300 epithelial and stromal
      features from objects comprising superpixels and several types of nuclei,
      including spatial relations among objects between and within each hierarchical
      level. We used penalized logistic regression and fivefold cross-validation to
      find optimal combinations of histological features in the year-4 biopsies.
      Feature data from the year-2 biopsies were fitted to a final model for
      independent validation. Two pathologists, blinded to treatment, scored each image
      for focal atrophy and histological features previously linked to 5AR1 treatment.
      RESULTS: Consensus classification by pathologists obtained a discrimination
      accuracy equivalent to chance. A 21-feature computer vision model gave a cross
      validation area under the curve of 0.97 (95% confidence interval [CI] 0.95-0.99)
      in the year-4 biopsies and 0.79 (95% CI: 0.65-0.92) in the set-aside year-2
      biopsies. Histology scores were not correlated with change in prostate-specific
      antigen level, serum dihydrotestosterone level or gland volume. Key features
      associated with dutasteride treatment included greater shape and colour
      uniformity in stroma, irregular clustering of epithelial nuclei, and greater
      variation in lumen shape. CONCLUSION: The present findings show that a computer
      vision approach can detect subtle histological effects attributable to
      dutasteride, resulting in a continuous measure of responsiveness to the drug that
      could eventually be used to predict individual patient response in the context of
      BPH treatment or cancer chemoprevention.

PMID- 29461668
TI  - Time-lapse imaging points towards a non-toxic, mainly immune-driven mode of
      action of ingenol mebutate in the treatment of anogenital warts.
AB  - Recently, it has been reported that ingenol mebutate (IM) is an effective
      treatment option for anogenital warts (AGW), inducing fast wart necrosis within
      24 hours in vivo. With regard to its mode of action, IM is thought to act both as
      an inducer of direct cytotoxic effects and immunologic mechanisms. To distinguish
      whether the wart necrosis is mainly caused by cytotoxic effects, or whether
      immune mechanisms are leading, we used time-lapse imaging to analyse IM-treated
      warts ex vivo over 24 hours. Ex vivo IM-treated warts, which have been detached
      from the immune system, did not show destructive necrosis, pointing towards a
      primarily immune-driven mode of action of IM in the treatment of AGW.

PMID- 29461669
TI  - Heat Shock Protein Reports on Proteome Stress.
AB  - Proper regulation of protein homeostasis (proteostasis) is essential to maintain
      cellular fitness. Proteome stress causes imbalance of the proteostasis, leading
      to various diseases represented by neurodegenerative diseases, cancers, and
      metabolic disorders. The biosensor community recently embarked on the development
      of proteome stress sensors to report on the integrity of proteostasis in live
      cells. While most of these sensors are based on metastable mutants of specific
      client proteins, a recent sensor takes advantage of the specific association of
      heat shock protein 27 with protein aggregates and exhibits a diffusive to
      punctate fluorescent change in cells that are subjected to stress conditions.
      Thus, heat shock proteins can be also used as a family of sensors to monitor
      proteome stress.

PMID- 29461670
TI  - Chiral 1,3,2-Diazaphospholenes as Catalytic Molecular Hydrides for
      Enantioselective Conjugate Reductions.
AB  - Secondary 1,3,2-diazaphospholenes have a polarized P-H bond and are emerging as
      molecular hydrides. Herein, a class of chiral, conformationally restricted
      methoxy-1,3,2-diazaphospholene catalysts is reported. We demonstrate their
      catalytic potential in asymmetric 1,4-reductions of alpha,beta-unsaturated
      carbonyl derivatives, including enones, acyl pyrroles, and amides, which
      proceeded in enantioselectivities of up to 95.5:4.5 e.r.

PMID- 29461671
TI  - Functional characterization of the citrus canker susceptibility gene CsLOB1.
AB  - Xanthomonas citri ssp. citri (Xcc) is an important plant-pathogenic bacterium
      that causes citrus canker disease worldwide. PthA, a transcriptional activator
      like (TAL) effector, directs the expression of the canker susceptibility gene
      CsLOB1. Here, we report our recent progress in the functional characterization of
      CsLOB1. Subcellular localization analysis of CsLOB1 protein in citrus protoplast
      revealed that CsLOB1 is primarily localized in the nucleus. We showed that CsLOB1
      expression driven by dexamethasone (DEX) in CsLOB1-GR transgenic plants is
      associated with pustule formation following treatment with DEX. Pustule formation
      was not observed in DEX-treated wild-type plants and in non-treated CsLOB1-GR
      transgenic plants. Water soaking is typically associated with symptoms of citrus
      canker. Weaker water soaking was observed with pustule formation in CsLOB1-GR
      transgenic plants following DEX treatment. When CsLOB1-GR-transgenic Duncan
      grapefruit leaves were inoculated with Xcc306DeltapthA4 and treated with DEX,
      typical canker symptoms, including hypertrophy, hyperplasia and water soaking
      symptoms, were observed on DEX-treated transgenic plant leaves, but not on mock
      treated plants. Twelve citrus genes that are induced by PthA4 are also stimulated
      by the DEX-induced expression of CsLOB1. As CsLOB1 acts as a transcriptional
      factor, we identified putative targets of CsLOB1 via bioinformatic and
      electrophoretic mobility shift assays. Cs2g20600, which encodes a zinc finger
      C3HC4-type RING finger protein, has been identified to be a direct target of
      CsLOB1. This study advances our understanding of the function of CsLOB1 and the
      molecular mechanism of how Xcc causes canker symptoms via CsLOB1.

PMID- 29461672
TI  - Antinuclear antibody profiling in uveitis.

PMID- 29461673
TI  - Identification of SCARA5 as a Potential Biomarker for Oral Squamous Cell
      Carcinoma using MALDI-TOF-MS Analysis.
AB  - PURPOSE: To find the potential biomarkers in the diagnostic model of oral and
      squamous cell carcinoma (OSCC), and to further validate the biomarker.
      EXPERIMENTAL DESIGN: With the MALDI-TOF-MS analysis between tissues from oral
      cancer patients and normal oral mucosa from healthy controls, scavenger receptor
      class A member 5 (scara5) is found to be potentially significant after searching
      the protein database. In addition, Immunohistochemical staining, PCR, ELISA, and
      Western blot technique are used to detect scara5 expression in clinical samples
      and cell lines. RESULTS: In this study, the results indicate that scara5
      expression is decreased in tumor group in the MALDI-TOF-MS analysis. Furthermore,
      down-regulation of scara5 expression is related with cell proliferation and
      invasion. Serum scara5 detection can discriminate OSCC samples from normal
      samples with high sensitivity. CONCLUSIONS AND CLINICAL RELEVANCE: Scara5 has the
      potential to be considered as a serum biomarker in the early diagnosis of OSCC.
      The clinical relevance of the study lies in finding the biomarker by proteomics
      and subsequently validating it with clinical samples and cell lines.

PMID- 29461674
TI  - Risk factors for postoperative intraretinal cystoid changes after peeling of
      idiopathic epiretinal membranes among patients randomized for balanced salt
      solution and air-tamponade.
AB  - PURPOSE: Epiretinal membranes (ERM) are macular disorders leading to loss of
      vision and metamorphopsia. Vitrectomy with membrane peeling displays the gold
      standard of care. Aim of this study was to assess risk factors for postoperative
      intraretinal cystoid changes in a study population randomized for balanced salt
      solution and air-tamponade at the end of surgery. METHODS: A prospective
      randomized study, including 69 eyes with idiopathic ERM. Standard 23-gauge three
      port pars plana vitrectomy with membrane peeling, using intraoperative optical
      coherence tomography (OCT), was performed. Randomization for BSS and air
      tamponade was performed prior to surgery. RESULTS: Best-corrected visual acuity
      improved from 32.9 letters to 45.1 letters 3 months after surgery. Presence of
      preoperative intraretinal cystoid changes was found to be the only risk factor
      for presence of postoperative intraretinal cystoid changes 3 months after surgery
      (p = 0.01; odds ratio: 8.0). Other possible risk factors such as combined
      phacoemulsification with 23G-ppv and membrane peeling (p = 0.16; odds ratio:
      2.4), intraoperative subfoveal hyporeflective zones (p = 0.23; odds ratio: 2.6),
      age over 70 years (p = 0.29; odds ratio: 0.5) and air-tamponade (p = 0.59; odds
      ratio: 1.5) were not found to be significant. CONCLUSION: There is strong
      evidence that preoperative intraretinal cystoid changes lead to smaller benefit
      from surgery.

PMID- 29461675
TI  - Improving eye care services with a lean approach.
AB  - PURPOSE: Effective provision of eye care services in government-financed
      hospitals is essential to balance the discrepancy between growing demand and
      limited resources. We aimed to improve efficiency of the treatment protocol for
      Nd:YAG laser posterior capsulotomy. Predetermined quality targets were a patient
      oriented and patient-safe approach and the development of a clinical care process
      with purposeful use of competences. METHODS: We utilized a lean process
      improvement methodology to develop a streamlined Nd:YAG laser posterior
      capsulotomy treatment protocol. A total of 206 patient visits were evaluated,
      where the lean-oriented treatment protocol was utilized in 158 of the visits and
      the conventional (CONV) protocol was followed in 48 of the visits. RESULTS: All
      baseline variables were comparable between the study groups. Compared to the CONV
      protocol, implementation of new operational principles shortened the total
      reception time per patient from 55:36 +/- 30:23; 12-136 min to 44:40 +/- 4:49; 37
      54 min (mean +/- SD; range, p = 0.040). The per hour number of patients and eyes
      treated in the operation room improved from 4.7 +/- 1.6; 2.6-8.4 patients and 5.5
      +/- 2.0; 3.5-11.3 eyes to 16.3 +/- 2.3; 14.3-19.4 patients (p < 0.001) and 18.0
      +/- 1.6; 16.8-20.4 eyes (p < 0.001). The time spent by the operating physician
      reduced from 8:19 +/- 3:06; 3:57-14:30 min to 3:01 +/- 1:00; 1:34-6:38 min in
      unilateral procedure (p < 0.001) and from 8:45 +/- 3:55; 5:52-14:10 min to 4:40
      +/- 2:03; 2:38-10:14 min in bilateral procedure (p < 0.006). Furthermore, the
      overall patient satisfaction grade improved from 17.3 +/- 1.04; 15-18 points to
      17.8 +/- 0.61; 15-18 points (p = 0.001). CONCLUSIONS: The lean approach improved
      the treatment protocol for Nd:YAG laser posterior capsulotomy with substantial
      reductions in lead times without compromising patient satisfaction.

PMID- 29461676
TI  - Clinical and prognostic associations of liver volume determined by computed
      tomography in acute liver failure.
AB  - BACKGROUND: Liver volume (LV) can be non-invasively determined from the analysis
      of computed tomography (CT) images, and in patients with acute liver injury (ALI)
      or failure (ALF), it can reflect the balance of structural collapse with hepatic
      regeneration. We examined its relation to cause of liver injury, measures of
      liver function and histopathological findings, and utility in prediction of
      complications and mortality. METHODS: Two hundred and seventy-three patients with
      ALF/ALI admitted to a specialist intensive care unit were studied. One hundred
      and ninety-nine patients (73%) had non-acetaminophen (NA) aetiologies and 74
      (27%) had acetaminophen-induced disease. LV and proportion of predicted LV (PLV%)
      were determined from admission CT imaging. RESULTS: LV and PLV% showed marked
      variation when aetiologic groups were compared (P < .0001), including loss in
      cases with indeterminate cause (LV 939 cm3 [IQR 680-1259], PLV% 56% [42-84]) and
      increase in Budd-Chiari syndrome (1891 cm3 [1601-2094], 121% [111-131]).
      Progression to high-grade encephalopathy was more common with smaller LV and PLV.
      A < 1000 cm3 threshold identified NA patients who later developed it with 93%
      (95%CI 83-98) specificity and odds ratio 10.6 (3.3-34.5) at median 5 days prior
      to onset, and risk of death in those with NA-drug-induced (DILI) or indeterminate
      disease with 91% (71-99) specificity and 63% (50-75) sensitivity. CONCLUSION: In
      patients with ALF/ALI, LV shows marked variation by the cause of disease, and in
      prognostic importance. In indeterminate and DILI cases, loss of volume to <1000
      cm3 may indicate irreversible liver injury and regenerative failure and serve as
      an early clinical predictor for the development of high-grade encephalopathy and
      death.

PMID- 29461677
TI  - Testicular asymmetry in healthy adolescent boys.
AB  - OBJECTIVES: To assess the presence of testicular asymmetry and the currently used
      threshold values in varicocoele management in a healthy adolescent population.
      SUBJECTS AND METHODS: We conducted an observational cross-sectional study from
      April 2015 until December 2016 in which we recruited 539 adolescent boys aged 11
      16 years. A clinical examination including testicular size measurement by
      ultrasonography was performed. Testicular volume (TV) was calculated using the
      Lambert formula (length * width * height * 0.71). The Testicular Atrophy Index
      (TAI) was calculated using the formula [(TV right - TV left)/largest TV] * 100.
      The data for all statistical analyses were stratified for Tanner stage for
      genital development (TSG) and pubic hair (TSP). Non-parametric tests were used to
      assess the difference between right and left TV, and the prevalence of a smaller
      left testis for the entire population, and between each TSG and TSP. Parametric
      tests were used to determine the difference in mean TAI between each TSG and TSP,
      and to compare the mean TAI to a test value of 0. RESULTS: Of the 539 recruited
      boys, we excluded 194 due to a current or past pathology, including varicocoeles,
      influencing normal (testicular) growth or due to incomplete data. Most boys were
      in the second Tanner stage, followed by the third Tanner stage. The mean (sd) age
      of the entire population was 13.33 (1.25) years. Of the 345 included participants
      the mean (sd) left TV was 7.67 (5.63) mL and right TV was 7.97 (5.90) mL. The
      mean (sd) TAI was 2.85 (17.00)%. In all, 203 (58.84%) boys had a smaller left
      testis and 142 (41.16%) had a smaller right testis. In all, 51 boys (14.78%) had
      a TAI >20%, 45 (13.04%) had a TV difference (TVD) of >2 mL with a deficit in left
      TV, and 69 (20.00)% had a TAI >20% or a TVD of >2 mL with a deficit in left TV.
      Related-samples Wilcoxon signed-rank test showed a significant difference in mean
      left and right TV for the entire population, and more specifically for TSG3 (P <
      0.001) and TSP3 (P = 0.004). A one-sample t-test showed a significant difference
      in the mean TAI vs the test value of 0 for the entire population (P = 0.002), and
      more specifically for TSG3 (P < 0.001) and TSP3 (P = 0.003). CONCLUSION:
      Testicular asymmetry, with a smaller left testis, was seen in a considerable
      number of healthy adolescents. One out of five adolescents had a smaller left
      testis and met one of the threshold values currently used in varicocoele
      management. Therefore, in left-sided unilateral inguinoscrotal pathology, a
      smaller ipsilateral testis in combination with a TAI of >20% and/or TVD of >2 mL
      requires careful interpretation and serial measurements of TV should always be
      performed. Furthermore, this study provides reference values for TV, TVD and TAI
      according to TSG and TSP for a healthy adolescent population.

PMID- 29461678
TI  - The relation between dietary intake and glaucoma: a systematic review.
AB  - PURPOSE: A common question of patients to their physician is what they can do
      themselves against glaucoma, except taking their daily medication. However, for
      ophthalmologists, it is often hard to give their patients an advice on their
      dietary intake. To help ophthalmologists in answering this question, an overview
      of the current scientific literature on the association of nutrients with
      glaucoma is presented. METHODS: A comprehensive systematic review was conducted
      in which articles published up to September 2017 were identified in PubMed and
      reference lists. Nutrients were categorized into minerals and trace elements,
      nutrition with antioxidative properties and omega-fatty acids. RESULTS: The
      literature search revealed a total of 407 articles of which a total of 46 met the
      inclusion criteria. Most of these articles studied the effect of nutrients on
      open-angle glaucoma. Many trace elements have been investigated in the
      literature, but the most interesting are selenium and iron (both may increase the
      risk of glaucoma). Investigated nutrients with antioxidative properties and omega
      fatty acids included glutathione, nitric oxide, carotenoids, flavonoids, and
      omega-3 and omega-6 fatty acids. Of these, glutathione, nitric oxide, and
      flavonoids had a significant protective effect on glaucoma. CONCLUSION: Intake of
      selenium and iron may increase the risk of glaucoma, though, only few studies
      have been done on this topic. Nitric oxide present in other dark green leafy
      vegetables seems to have a beneficial effect on glaucoma. However, the evidence
      for an association of dietary intake with glaucoma is still not strong. More
      (longitudinal and randomized clinical trials) studies are required to make the
      presented findings clinically applicable.

PMID- 29461680
TI  - Reducing-Autophagy Derived Mitochondrial Dysfunction during Resveratrol Promotes
      Fibroblast-Like Synovial Cell Apoptosis.
AB  - In rheumatoid arthritis patients, the fibroblast-like synovial cells (FLS) growth
      is not controlled normally, but is similar to the tumor cells proliferation in
      histology. Our previous studies have shown that resveratrol inhibits the
      proliferation of FLS and promotes FLS apoptosis. However, the molecular
      mechanisms involved in resveratrol-induced FLS apoptosis have not been determined
      yet. Here, we showed that the FLS cell viability (following pretreatment with 5
      uM H2 O2 for 24 hr) exhibited better proliferation performance than at other
      concentrations via the CCK-8 assay. The cell apoptotic rate increased with the
      increasing concentration of resveratrol (0, 40, 80, 160, 320 MUM), as detected by
      TdT-mediated dUTP nick-end labeling (TUNEL) staining and western blotting.
      Furthermore, the expression level of autophagy-related proteins (LC3A/B, ATG-5)
      decreased with the increased concentration of resveratrol, as determined by
      immunofluorescence and western blot analysis. We also showed that resveratrol
      induced FLS mitochondrial morphology change. Moreover, mitochondrial function
      detection showed that the mitochondrial membrane potential was lost with the
      increased concentration of resveratrol as examined by the JC-1 assay. The
      production of ATP in cells was positively and negatively correlated with the
      resveratrol concentration. Simultaneously, the intracellular calcium release and
      calcium influx decreased gradually with the increase in resveratrol
      concentration. Therefore, we proposed that resveratrol can reduce the level of
      autophagy in FLS. The decrease in the autophagy level can lead to the
      accumulation of reactive oxygen species, which may result in mitochondrial
      dysfunction and promotion of FLS apoptosis. Anat Rec, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29461679
TI  - Potential link between sporadic cerebral amyloid angiopathy and vision loss: a
      case report.

PMID- 29461681
TI  - United States Model Midwifery Legislation and Regulation: Development of a
      Consensus Document.
AB  - INTRODUCTION: Midwifery is defined and regulated across all 50 United States.
      However, states' regulations vary markedly, creating confusion for policy makers
      and consumers, and can limit services to women. In 2011, the International
      Confederation of Midwives released Global Standards for Midwifery Education,
      Regulation, and Association, providing guidance for international midwifery for
      the first time. US organizations representing midwifery education, regulation,
      and professional associations (US MERA) agreed to work together on common goals.
      METHODS: The purpose of this modified Delphi study, conducted by US MERA, was to
      develop a consensus document on principles of model US midwifery legislation and
      regulation. Expert panelists (N = 51) across maternal and child health care
      professions and consumer groups participated over several iterative rounds.
      RESULTS: The final document establishes guiding principles for US midwifery
      regulation, including regulatory authority, education, qualifications,
      regulation, registration and licensure, standards of practice and conduct,
      complaints, and third-party payment for services. DISCUSSION: As more US states
      recognize and license midwives of all credentials and in every practice setting,
      we can envision a time when equity, informed choice, safety, and seamless access
      to quality midwifery care will be the right of every birthing family.

PMID- 29461682
TI  - Spectacle use after routine cataract surgery and vision-related activity
      limitation.
AB  - PURPOSE: To explore the relationship between acquisition of new spectacles after
      routine cataract surgery and vision-related activity limitation (VRAL)
      postoperatively. METHODS: This cohort study with intervention (survey) included
      1329 patients in Sweden who had undergone a second-eye cataract surgery during
      March 2013. Data from the Swedish National Cataract Register were used, including
      evaluations of VRAL through the Catquest-9SF questionnaire before and 3 months
      after cataract surgery. Five months after the second-eye surgery, patients
      completed another five-item questionnaire about spectacle use preoperatively and
      postoperatively including an item on surgeons' advice about the need for
      spectacles. These responses were linked to the Rasch-analysed Catquest-9SF data
      to identify correlations with VRAL. RESULTS: A total of 1239 patients finally
      participated in the study after excluding those who did not fulfil the inclusion
      criteria. Patients who were advised about the need for spectacles postoperatively
      (n = 387) had a greater (p = 0.039) improvement in the postoperative VRAL
      compared to patients who were not advised (n = 691). Patients who obtained new
      spectacles postoperatively (n = 512) also had greater improvement (p = 0.032)
      compared to those who did not (n = 724). CONCLUSION: The average improvements in
      the VRAL after surgery were significantly higher for patients who obtained new
      distance spectacles postoperatively and for patients who were informed about the
      need for spectacles by their practitioners.

PMID- 29461683
TI  - Therapeutic antibiotic serum concentrations by two blood collection methods
      within the pediatric patient: A comparative effectiveness trial.
AB  - Repeated venipunctures and fingersticks to confirm serum drug concentrations
      cause pain and dissatisfaction for pediatric patients and their families. In many
      organizations, the standard of care to obtain therapeutic serum drug
      concentrations by peripheral venipuncture or capillary fingerstick, even when the
      patient has an existing peripheral intravenous catheter (PIV) or central venous
      catheter (CVC). The primary objective of this study was to assess agreement
      between serum tobramycin/vancomycin concentrations collected from a CVC or PIV,
      versus venipuncture or fingerstick. Among hospitalized pediatric patients (age 3
      months to 22 years), 36 paired blood samples were collected. Serum trough
      vancomycin and random tobramycin concentrations were compared between peripheral
      intravenous or CVC samples, and venipuncture or fingerstick samples within the
      same patient. A strict sampling protocol for obtaining the samples was followed,
      that included collection of the CVC/PIV sample before the venipuncture or
      fingerstick, less than 2 min between collections of samples from the different
      sites, and a strict volume-based flush and waste protocol. Concordant correlation
      coefficients demonstrated substantial agreement between CVC/PIV and
      venipuncture/fingerstick concentrations for vancomycin (n = 17) and tobramycin (n
      = 19) (Rc = 0.982 for both). Bland-Altman analyses demonstrated good overall
      between-method agreement within subjects and minimal bias. Consequently, using a
      lumen volume-based flush and waste protocol, children with indwelling catheters
      may not require additional venipunctures and/or fingersticks for confirmation of
      drug concentrations while hospitalized, improving the quality of care and patient
      satisfaction.

PMID- 29461684
TI  - How Patterns of Learning About Sexual Information Among Adolescents Are Related
      to Sexual Behaviors.
AB  - CONTEXT: Parents, peers and media are informal sources of sexual information for
      adolescents. Although the content of sexual information communicated by these
      sources is known to vary, little is known about what adolescents report actually
      learning from each source. METHODS: Data from 1,990 U.S.14-17-year-olds who
      participated in an online survey in 2015 were used to assess learning about four
      topics (sex, condoms, hormonal birth control and romantic relationships) from
      three informal sources (parents, peers, and television and movies). Gender and
      race differences in learning by source and topic were assessed using t tests.
      Following a factor analysis, learning about all topics was grouped by source, and
      regression analyses were conducted to examine associations between learning from
      each source and three outcomes: sexual activity, condom use and hormonal birth
      control use. Models included interactions between information sources and race
      and gender. RESULTS: White adolescents reported learning more from parents and
      less from media than black adolescents. Compared with males, females learned more
      about hormonal birth control and less about condoms from their parents, and more
      about relationships from peers and media. Learning from parents and from peers
      were positively associated with adolescents' sexual activity (unstandardized
      coefficients, 0.26 and 0.52, respectively). Learning from parents was positively
      associated with condom use (odds ratio, 1.5). CONCLUSION: Adolescents' learning
      about sex from informal sources varies by race and gender. Future research should
      examine whether sexual health interventions and message development can
      capitalize on these differences.

PMID- 29461685
TI  - Enzymatic Production of Biodiesel: Strategies to Overcome Methanol Inactivation.
AB  - Lipase-catalyzed transesterification of triglycerides and alcohols to obtain
      biodiesel is an environmentally friendly and sustainable route for fuels
      production since, besides proceeding in mild reaction conditions, it allows for
      the use of low-cost feedstocks that contain water and free fatty acids, for
      example non-edible oils and waste oils. This review article reports recent
      advances in the field and focus in particular on a major issue in the enzymatic
      process, the inactivation of most lipases caused by methanol, the preferred acyl
      acceptor used for alcoholysis. The recent results about immobilization of enzymes
      on nano-materials and the use of whole-cell biocatalysts, as well as the use of
      cell-surface display technologies and metabolic engineering strategies for
      microbial production of biodiesel are described. It is discussed also insight
      into the effects of methanol on lipases obtained by modeling approaches and
      report on studies aimed at mining novel alcohol stable enzymes or at improving
      robustness in existing ones by protein engineering.

PMID- 29461686
TI  - ATP-binding cassette subfamily A, member 4 intronic variants c.4773+3A>G and
      c.5461-10T>C cause Stargardt disease due to defective splicing.
AB  - PURPOSE: Inherited retinal dystrophies (IRDs) represent a group of progressive
      conditions affecting the retina. There is a great genetic heterogeneity causing
      IRDs, and to date, more than 260 genes are associated with IRDs. Stargardt
      disease, type 1 (STGD1) or macular degeneration with flecks, STGD1 represents a
      disease with early onset, central visual impairment, frequent appearance of
      yellowish flecks and mutations in the ATP-binding cassette subfamily A, member 4
      (ABCA4) gene. A large number of intronic sequence variants in ABCA4 have been
      considered pathogenic although their functional effect was seldom demonstrated.
      In this study, we aimed to reveal how intronic variants present in patients with
      Stargardt from the same Swedish family affect splicing. METHODS: The splicing of
      the ABCA4 gene was studied in human embryonic kidney cells, HEK293T, and in human
      retinal pigment epithelium cells, ARPE-19, using a minigene system containing
      variants c.4773+3A>G and c.5461-10T>C. RESULTS: We showed that both ABCA4
      variants, c.4773+3A>G and c.5461-10T>C, cause aberrant splicing of the ABCA4
      minigene resulting in exon skipping. We also demonstrated that splicing of ABCA4
      has different outcomes depending on transfected cell type. CONCLUSION: Two
      intronic variants c.4773+3A>G and c.5461-10T>C, both predicted to affect
      splicing, are indeed disease-causing mutations due to skipping of exons 33, 34,
      39 and 40 of ABCA4 gene. The experimental proof that ABCA4 mutations in STGD
      patients affect protein function is crucial for their inclusion to future
      clinical trials; therefore, functional testing of all ABCA4 intronic variants
      associated with Stargardt disease by minigene technology is desirable.

PMID- 29461687
TI  - Efficacy of elbasvir and grazoprevir in participants with hepatitis C virus
      genotype 4 infection: A pooled analysis.
AB  - BACKGROUND & AIMS: The aim of this integrated analysis was to assess the efficacy
      of the once-daily combination of elbasvir 50 mg and grazoprevir 100 mg, with and
      without ribavirin in HCV genotype 4 (GT4)-infected participants enrolled in the
      Phase 2/3 clinical programme with elbasvir/grazoprevir. METHODS: Treatment-naive
      and treatment-experienced participants 18 years of age or older with chronic HCV
      GT4 infection and baseline HCV RNA >=10 000 IU/mL were included in the analysis.
      The analysis population was the full analysis set (FAS; all participants who
      received at least 1 dose of study medication) and a total of 155 HCV GT4
      participants were evaluated. The primary endpoint was sustained virologic
      response at week 12 (SVR12; HCV RNA less than the lower limit of quantitation at
      12 weeks after the completion of study therapy). RESULTS: Overall, among GT4
      infected participants treated with 12 or 16 weeks of elbasvir/grazoprevir +/-
      ribavirin, the SVR12 efficacy rates were 96.4% (107/111) in treatment-naive
      participants and 88.6% (39/44) in treatment-experienced participants. The SVR12
      rates were 96.0% (97/101) in treatment-naive participants treated with 12 weeks
      of elbasvir/grazoprevir and 100% (8/8) in treatment-experienced participants
      treated with 16 weeks of elbasvir/grazoprevir plus ribavirin. Efficacy was not
      impacted by GT4 subtype. CONCLUSIONS: The regimens of 12 weeks of
      elbasvir/grazoprevir without ribavirin, and 16 weeks of elbasvir/grazoprevir plus
      ribavirin, were efficacious in HCV GT4-infected treatment-naive and treatment
      experienced participants respectively. Baseline NS5A resistance-associated
      substitutions did not impact the efficacy of elbasvir/grazoprevir in GT4-infected
      participants.

PMID- 29461688
TI  - Spontaneous blinking activity in blind patients.

PMID- 29461690
TI  - Numerical research on the biomechanical behaviour of braided stents with
      different end shapes and stent-oesophagus interaction.
AB  - Quasi-static and dynamic numerical analyses are carried out by referring to
      computational models of commercial self-expandable braided stents with 3 commonly
      used end shapes, to evaluate the influence of different end shapes of stent on
      the biomechanical interaction between stent and oesophagus. The end shape has no
      influence on the equivalent stress, but has a great influence on the contact
      stress in the narrowest zone of the oesophagus-neoplasm system. However, the end
      shapes have significant effect on the equivalent stress and the contact stress in
      the healthy area of the oesophagus in contact with the stent ends. The results
      show that the maximum equivalent stress of the oesophagus occurs in the zone
      contact with the cup-shaped end and the maximum contact stress occurs in the zone
      contact with the edge of the trumpet-shaped stent end. Moreover, the stent
      apposition is almost not affected by the end shapes. Although small zones with an
      incomplete stent apposition appear in the transition zones of spherical-cup
      shaped stent, such occurrence might not contribute to stent malapposition or
      stent migration. Therefore, these stents with 3 types of end shapes all have good
      stent apposition. Finally, the numerical simulation results can be used to assess
      the mechanical performance of stents with different end shapes, the effectiveness
      of stent expansion therapy, and the possibility of complications after stent
      implantation.

PMID- 29461689
TI  - Clinical associations between allergies and rapid eye movement sleep
      disturbances.
AB  - BACKGROUND: Allergic rhinitis, an immunoglobulin E inflammatory condition
      including nasal congestion, obstruction, sneezing, pruritus, and fatigue
      symptoms, has significant impact on quality of life and impairs sleep. Sleep
      disordered breathing (SDB) patients often have normal all-night apnea-hypopnea
      (AHI) or respiratory-disturbance (RDI) indices on polysomnography (PSG). We
      hypothesized that the rapid eye motion-respiratory disturbance index (REM-RDI)
      may be a novel predictor of allergic status. METHODS: A retrospective analysis of
      100 patients compared REM-RDI results in 67 allergen-positive patients with 33
      nonallergic patients who presented with nasal blockage. Subjects completed STOP
      Bang(c), 22-item Sino-Nasal Outcome Test (SNOT-22)(c), and Epworth Sleepiness
      Scale(c) questionnaires and underwent skin-prick testing (SPT) and PSGs including
      REM-RDI values. Using multivariate logistic regression models, we evaluated
      relationships between allergic status and sleep parameters while controlling for
      possible confounders including body mass index (BMI). RESULTS: Using REM-RDI as
      the outcome of interest, allergen-positive patients were 3.92 times more likely
      to have REM-RDI values in a moderate/severe range (>=15 events/hour); and
      patients with moderate/severe REM-RDI values were more likely to be allergen
      positive (p < 0.05). Allergic status was not significantly related to all-night
      AHI, RDI, or REM-AHI. BMI was not significantly related to REM-RDI. STOP-Bang(c)
      was related to allergy status (p = 0.02) and REM-RDI (p < 0.01). Allergic
      patients had increased REM latency and less total amount of REM. CONCLUSION: We
      revealed significant bidirectional associations between allergen positivity and
      increased REM-RDI values independent of BMI, AHI, RDI, and REM-AHI. Allergic
      inflammation and REM-RDI data may play important roles in diagnosing and treating
      fatigued SDB patients and as objective perioperative safety and outcomes
      measures.

PMID- 29461691
TI  - Solute-Stationary Phase Interaction in Chiral Chromatography.

PMID- 29461692
TI  - The Role of Chromatography in Alzheimer's Disease Drug Discovery.

PMID- 29461693
TI  - Characterization of the Kinetic Performance of Silica Monolithic Columns for
      Reversed-Phase Chromatography Separations.

PMID- 29461695
TI  - Uncertainty Evaluation in Chromatography.

PMID- 29461694
TI  - Recent Advances in the Characterization and Analysis of Therapeutic
      Oligonucleotides by Analytical Separation Methods Coupling with Mass
      Spectrometry.

PMID- 29461696
TI  - Comprehensive Two-Dimensional Hydrophilic Interaction Chromatography x Reversed
      Phase Liquid Chromatography (HILIC x RP-LC) Theory, Practice, and Applications.

PMID- 29461697
TI  - Sample Preparation for Thin Layer Chromatography.

PMID- 29461698
TI  - Modeling of HPLC Methods Using QbD Principles in HPLC.

PMID- 29461700
TI  - Looking back with pride and joy.

PMID- 29461699
TI  - Feeling inspired.

PMID- 29461701
TI  - Board membership: It's not for the faint of heart.

PMID- 29461702
TI  - Reliability of psychometric instruments.

PMID- 29461703
TI  - Much left to learn about Zika.

PMID- 29461704
TI  - Comparing Personal Health Practices: Individuals with mental illness and the
      general Canadian population.
AB  - OBJECTIVE: Individuals with mental illness often live in chronic poverty, which
      is associated with personal health practices such as tobacco use and poor
      nutrition that disrupt physical health. The purpose of our study was to examine
      whether differences exist in personal health and health practices - related to
      nutrition, physical activity, smoking, alcohol consumption and sleep - between a
      cohort of individuals with mental illness in southwestern Ontario and the general
      Canadian population. METHOD: The study sample consisted of 250 individuals who
      had had a psychiatric diagnosis for at least one year. We conducted a structured
      quantitative interview with each person to gather information about their
      personal health and health practices, using question wording from the National
      Population Health Survey and the Canadian Community Health Survey. We calculated
      95% confidence intervals for our results and used them to compare our data with
      Canadian norms. RESULTS: Individuals with mental illness are significantly more
      likely than the general population to have a poor diet, experience poor sleep and
      consume alcohol in excess. CONCLUSION: It is important for nurses, health-care
      organizations and policy-makers to be aware that a number of factors may be
      influencing the personal health and health practices of individuals with mental
      illness and that this population may require different health promotion
      strategies to support a healthy lifestyle.

PMID- 29461705
TI  - Champions for the cause.

PMID- 29461706
TI  - Nature therapy at work.

PMID- 29461707
TI  - Are we prepared for marijuana to go mainstream?.

PMID- 29461708
TI  - Our food supply is still salty to a fault.

PMID- 29461709
TI  - Translating Heart Health Knowledge into Action: A Vascular and Risk Reduction
      Program for Women Aged 35 to 65 Years.
AB  - BACKGROUND: Globally, about 8.6 million women die each year due to cardiovascular
      disease with cerebral vascular disease being the third leading cause of death in
      women. The province of New-foundland and Labrador has one of the highest rates of
      vascular disease in comparison to the rest of Canada. Women in New-foundland and
      Labrador have higher rates of vascular disease than their female cohorts across
      Canada. A vascular risk reduction programfor women aged 35 to 65 years was
      developed and implemented in a rural and an urban setting. PURPOSE: An evaluation
      of the program was conducted to assess the impact of the program on participants'
      satisfaction and to assess how women were able to apply acquired knowledge into
      their everyday lives to improve their vascular health. PROCEDURE: A thematic
      analysis of qualitative data collected during tvo focus groups (N=19) was
      completed. FINDINGS: Three core themes were identified that captured the
      experiences of the women who participated in the program including Solidifying
      One's Risk, Translating Knowledge into Action, and Making a Change. IMPLICATIONS:
      Implementation of community-based vascular education programs must consider the
      context in which the program is delivered, the population's unique needs, and
      existing resources if they are to be successful in sustaining healthy lifestyle
      behaviours known to decrease one's riskfor vascular disease.

PMID- 29461710
TI  - A Multidisciplinary Approach to the Development and Implementation of Best
      Practices Usng an Innovative Clinical Pathway for the Management of Cardiac
      Arrest Patients with Cognitive Dysfunction: A Case Study.
AB  - Out-of-hospital cardiac arrest (OOHCA) affects 20 to 140 people per 100,000
      globally with survival rangingfrom 2% to 11% (Meaney et al., 2013). Patients who
      have survived, but have been left with cognitive impairments due to anoxic brain
      injury should be offered early identification and initiation of rehabilitation
      needs during their admission to mitigate the impact of these deficits (Moulaert
      et al., 2011). Unfortunately, most cardiac survivors do not receive specialized
      rehabilitation during their acute hospitalization and there are no clinical
      pathways that currently exist to guide acute care practitioners regarding the
      appropriate timing of cognitive screens and early rehabilitation interventions.
      This tertiary care institution designed and implemented a clinical pathway and
      patient and family education tools, which have systematically improved the
      identification and treatment ofpatients requiring cognitive rehabilitation. In
      this paper, the authors discuss the pathway/tool development and use a case study
      to highlight these interventions.

PMID- 29461711
TI  - Risk Factors and Best Practices for the Prevention of Post-Cardiac Surgery
      Surgical Site Infections in a Tertiary Care Centre.
AB  - BACKGROUND: Post-cardiac surgery surgical site infections (SSIs) pose devastating
      consequences in terms of morbidity and mortality to patients. OBJECTIVE: To
      examine current risk factors and best practice perioperative care for prevention
      of SSI following cardiac surgery through the lens of the demographic/clinical
      characteristics of patients who developed post-cardiac surgery SSIs at a major
      tertiary care institution, and to identify where documentation is lacking and
      could be improved to better serve clinical practice. METHODS: A literature review
      on post-cardiac surgery SSI prevention and risk factors was performed. These risk
      factors were examined through a retrospective chart review of the population of
      patients who developed SSIs during the study period. RESULTS: The study
      population was characterized by a high prevalence of riskfactors including age,
      diabetes, obesity, operative time, blood glucose control, surgical re
      exploration, blood transfusions, and emergency context, as well as differences
      from best practice guidelines such as preoperative showering. Compared to other
      populations in the literature, several ofthese risk factors were more prevalent
      at the study site than in the other comparable populations. CONCLUSION: The
      patient population had a relatively high prevalence of riskfactors, and the care
      received by these patients varied in some ways from best practices. Using best
      practice guidelines, known risk factors, and the data specific to the institution
      can provide insightsfor analysis and practice improvement efforts in the form of
      identifying at-risk patients, improving adherence to best practice guidelines,
      targeting areas to focus care efforts, and improving clincal documentation.

PMID- 29461712
TI  - Margaret F. Washburn in The American Journal of Psychology: A Cognitive
      Precursor?
AB  - In the early 20th century, Margaret F. Washburn (1871-1939) produced numerous
      studies on perception, affective value of stimulus, memory, emotions, and
      consciousness. This experimental work was published in The American Journal of
      Psychology. The purpose of this article is to analyze the temporal evolution of
      these kinds of experiments and relate them to Washburn's theoretical production.
      Contrary to other views, Washburn's experimental evolution follows a logical
      sequence and has a strong inner coherence. Among other reasons, the lack of a
      scientific and social framework to the study of the mind has tended to overshadow
      large areas of Washburn's thought. However, both the work published in AJP and
      the methods used in experiments provide reasons to consider.Washburn one of the
      precursors of contemporary cognitive psychology.

PMID- 29461713
TI  - Edwin G. Boring: The Historian's Path in the Pages of The American Journal of
      Psychology.
AB  - Although he is best known for his classic textbook, A History of Experimental
      Psychology, Edwin Garrigues Boring published dozens of articles in The American
      Journal of Psychology and used its various formats to guide the discipline in the
      early 20th century. This report reviews a small sample of his publications,
      including obituaries, notes, and experimental articles, and presents them in
      historical and biographical context. A central objective is to show how Boring
      shared the values of his structuralist training with the emerging American
      schools and how time allowed him to reconsider his approach to history and the
      legacy of his iconic mentor, Edward Bradford Titchener.

PMID- 29461714
TI  - Failures Due to Interruptions or Distractions: A Review and a New Framework.
AB  - Interruptions of ongoing activities have spread since the development of and
      global increase in technology use and the general speeding in pace we all
      experience every day. Their negative effects are well known: decline in
      performance and emotional distress. However, the literature still needs to shed
      light on the exact cognitive mechanisms involved in the way users decide to reply
      to an interruption, on the effects of interruptions of different durations, and
      on factors influencing reactivation of task schemata and goals at resumption.
      Therefore, the aim of this article is to review the existing literature and
      models, uncover unresolved challenges, and propose new ways to confront them. We
      first review the substantive findings of recent decades from different domains
      (human-computer interaction, cognitive and experimental psychology, ergonomics),
      and their respective methodological and theoretical contributions. Then we
      propose a general and operationalized definition of an interruption; review the
      different cognitive models of attention, executive control, and working memory
      that best explain the impact of interruptions; describe current challenges and
      questions that remain open for future studies; and finally propose an integrative
      research framework, the DETOUR, which clarifies the cognitive processes at play
      during interruptions. We believe this work can directly affect the current state
      of the art, leading to new fundamental studies and applied solutions for the
      management of interruptions.

PMID- 29461715
TI  - Modern Speed-Reading Apps Do Not Foster Reading Comprehension.
AB  - New computer apps are gaining popularity by suggesting that reading speeds can be
      drastically increased when eye movements that normally occur during reading are
      eliminated. This is done using rapid serial visual presentation (RSVP), where
      words are presented 1 at a time, thus preventing natural eye movements such as
      saccades, fixations, and regressions from occurring. Al- though the companies
      producing these apps suggest that RSVP reading does not yield comprehension
      deficits, research investigating the role of eye movements in reading documents
      shows the necessity of natural eye movements for accurate comprehension. The
      current study explored variables that may affect reading comprehension during
      RSVP reading, including text difficulty (6th grade and 12th grade), text
      presentation speed (static, 700 wpm, and 1,000 wpm), and working memory capacity
      (WMC). Consistent with recent work showing a tenuous relationship between
      comprehension and WMC, participants' WMC did not predict comprehension scores.
      Instead, comprehension was most affected by reading speed: Static text was
      associated with superior performance, relative to either RSVP reading condition.
      Furthermore, slower RSVP speeds yielded better verbatim comprehension, and faster
      speeds benefited inferential comprehension.

PMID- 29461716
TI  - Parallel Interactive Processing as a Way to Understand Complex Information
      Processing: The Conjunction Fallacy and Other Examples.
AB  - Parallel interactive processing (PIP) represents an approach in which specific
      context generates interactive relationships between general attributes. This
      article summarizes previous research that demonstrates how such relationships
      influence inference making in categorization. This is followed by evidence that
      the approach can be extended to other areas of cognition, including probability
      judgments. PIP was successful in fitting data that revealed the prevalence of the
      conjunction fallacy as well as other probability estimation data. PIP provided
      better fits overall than the signed summation model and the configural weighted
      average model. The quantum probability model provided good fits for the
      conjunction fallacy data but not for other probability judgments.

PMID- 29461718
TI  - The Birth of a New Branch of Medicine: Psychiatry.
AB  - Psychiatric treatment prior to 1955 seemed to be at a standstill. All kinds of
      treatments, including surgical ones, were used ineffectively. Then suddenly, out
      of nowhere, a new treatment -chlorpromazine - created a worldwide revolution.
      Here is what we saw in Delaware. It was not much different in the rest of the
      world. Patients improved and were rapidly dischargedfrom mental institutions
      causing workforce reductions. I was sitting on a state employee job application
      evaluation committee and witnessed these events. It was also exciting to see
      rapid changes in administration at the state hospital. Since what happened in
      Delaware also happened nationally, this was a national event and should be
      recognized as such. The following few pages are to remember the details. Major
      changes made psychiatry more of an accepted medical specialty. Psychiatrists are
      no longer "outsiders." I would be glad to answer any questions about the
      information presented here.

PMID- 29461719
TI  - Critical care nursing north of the 6oth Parallel: A qualitative pilot study.
AB  - BACKGROUND: There is growing knowledge specif c to remote, rural and northern
      nursing practice in Canada's north. However, there is limited research that
      specifically addresses the experiences of critical care nurses working in
      Canada's northern communities. PURPOSE: The purpose of this pilot study was to
      begin to explore and better understand the experiences of Canadian nurses
      providing critical care to patients and families in intensive care units north of
      the 60th parallel. STUDY DESIGN: An interpretive phenomenological analysis was
      used. METHOD: Telephone interviews were conducted with three registered nurses
      currently employed in the designated intensive care unit on a full-time, part
      time or casual basis. Interviews were thematically coded and analyzed. Member
      checks were used to ensure thick description for this pilot study was obtained.
      FINDINGS: The following themes evolved through the interpretive phenomenological
      analysis process, Going North, The Role of the Northern ICU Nurse, Challenges,
      Support, Positive Aspects of the Experience, and The Northern Experience.
      CONCLUSIONS: Threaded throughout the main themes, participants made reference to
      "making it work". Making it work was reflected in how the participants described
      managing limited resources (particularly human resources), working within an
      expanded scope and managing the expectation that "the ICU nurse can do it."

PMID- 29461720
TI  - Changing laws on medical assistance in dying: Implications for critical care
      nurses.
AB  - In February 2015, the Supreme Court of Canada released its decision in the Carter
      v. Canada (Attorney General) case, declaring section 241(b) and section 14 of the
      Criminal Code invalid, and granting a one-year suspension on that declaration to
      enable the Parliament of Canada to respond. In June 2016, Bill C-14: An Act to
      Amend the Criminal Code and Make Related Amendments to Other Acts (Medical
      Assistance in Dying) was passed after much debate in the House of Commons and
      Senate of Canada. Brief summaries of the Carter v. Canada case and the new
      federal law are provided and questions regarding medical assistance in dying are
      explored. The implications of the case and the new law for critical care nurses
      are also examined, including the need for nurses to attend to legislative
      changes, the need for education about the roles of nurses in medical assistance
      in dying, particularly what can be learned from other jurisdictions, and the
      importance of understanding the concept of conscientious objection.

PMID- 29461717
TI  - Targeted Next Generation Sequencing with ThyroSeq v2.1 for Indeterminate Thyroid
      Nodules in Clinical Practice.
AB  - OBJECTIVE: To determine if patients elect molecular testing over diagnostic
      surgery or repeat fine needle aspiration for indeterminate thyroid nodules. Can
      ThyroSeq v2.1 molecular testing reduce diagnostic thyroid surgery and rule out
      cancer? STUDY DESIGN: Retrospective review Setting: Single institution, single
      practice surgeon. SUBJECTS AND METHODS: Fifteen month retrospective review of
      indeterminate thyroid nodules that went on to ThyroSeq v2.1 testing. RESULTS: 286
      patients met American Thyroid Association guideline criteria for surgeon-
      performed, ultrasound-guided fine needle aspiration for a thyroid nodule with on
      site cytopathology. The indeterminate (Bethesda III or IV) fine needle aspiration
      cytology rate was 9.1 percent. Prevalence of malignancy in indeterminate nodules
      was 19 percent. 26/26 (100 percent) patients with indeterminate thyroid nodules
      elected molecular testing. 16 patients had no mutation, 9 had one or more
      mutations, and I had no result. 16 of 25 (64 percent) patients with no mutation
      elected not to undergo diagnostic surgery for indeterminate thyroid nodules.
      CONCLUSIONS: Patients demonstrated a strong preference for molecular testing
      instead of diagnostic thyroid surgery for indeterminate thyroid nodules. All
      patients in this series, 25/25 (100 percent) with indeterminate thyroid nodules
      elected molecular testing instead of repeat biopsy or diagnostic thyroid surgery.
      16 of 25 (64 percent) patients tested had no mutation. All 16/16 (100 percent)
      patients with no mutation on ThyroSeq "rule out" testing elected active
      surveillance rather than surgery or biopsy, reducing diagnostic surgery. The risk
      of malignancy among mutation negative patients was not definitively established.
      There are a number of factors currently that may mute the power of "rule in"
      testing.

PMID- 29461721
TI  - Intensive care nurses' assessment of pain in patients who are mechanically
      ventilated: How a pilot study helped to influence practice.
AB  - BACKGROUND: Pain is a common experience among patients in intensive care units
      (ICUs). Many patients in ICUs have difficulty communicating their pain because of
      mechanical ventilation, and issues can arise when the nurse attempts to interpret
      the severity of pain,and work towards effective pain management. PURPOSE: The aim
      of this study was to determine the suitability of the Critical-Care Pain
      Observation Tool (CPOT) as an assessment tool to be used by ICU nursing staff to
      assess pain in adult. patients who are mechanically ventilated. METHODS: This
      pilot study was descriptive in design and employed both quantitative and
      qualitative methods. Quantitative data resulted from the CPOT scores obtained. In
      addition, a data collection sheet, developed by the authors, recorded sedation
      and analgesia used and interventions provided. This separate sheet was completed
      each time the CPOT was used. Nurses were asked to evaluate the CPOT using a
      Likert scale. Qualitative data were collected through open-ended questions
      related to using the CPOT Results. Twenty-three participants each assessed pain
      five times in a total of 23 patients using the CPOT over a 12-hour shift. Nurses
      stated the tool was easy to use and that it would be helpful to them. CONCLUSION:
      The results of this pilot study contributed to the decision to implement the CPOT
      at the study ICUs. The systematic use of a tool may promote more goal-directed
      management of pain.

PMID- 29461722
TI  - Leadership Challenge No.3.
AB  - ON A WALL THAT HELPS CREATE THE "WELCOME WINDOW" PORTION OF OUR FRONT DESK IS A
      FRAMED DOCUMENT ENTITLED "FIJAL AND ASSOCIATES STATEMENT OF PHILOSOPHY." It
      begins with a mission statement consisting of just two sentences followed by more
      detailed descriptions of how our products, patients, staff, business principles,
      future and leadership will exemplify and support that mission. I wrote it in
      1987.

PMID- 29461723
TI  - Right marketing strategy will attrac new patients.

PMID- 29461724
TI  - How to hire your dental team.

PMID- 29461725
TI  - Many CDS members go above, beyond for access to care.

PMID- 29461726
TI  - How to handle a negative review on social media.

PMID- 29461727
TI  - We can't do it alone.
AB  - SINCE 2013, THE CDS FOUNDATION HAS PROVIDED FREE DENTAL CARE TO THE UNDERSERVED
      AT ITS CLINIC IN WHEATON.

PMID- 29461728
TI  - Keeping time with Anthony Maoloni.

PMID- 29461729
TI  - Introduction to the annual report 2016: a joint venture in the field of Acute
      ENT.

PMID- 29461730
TI  - Face and neck: airway and sensorial capacities.
AB  - Face and neck: airway and sensorial capacities. For the assessment and the
      management of face and neck trauma knowledge of the neuro-anatomy and physiology
      of the ear, nose, throat (ENT) and head and neck (HN) region and structures is
      essential, as this area is particularly vulnerable to injury. Indeed, the complex
      anatomy and physiology in this specific area supports important basic functions.
      In addition, this review elaborates on upper airway and sensorial capacities.
      Upper airway dimensions are influenced by bony and soft tissues. Age is of
      fundamental importance in the upper airway assessment, as significant differences
      in size and proportions apply in children and adults. The cranial nerves (CN)
      supply motor, sensory ad special sensory fibres to the upper airway. Injury of
      the CN is a frequent complication of trauma.

PMID- 29461731
TI  - Emergency care in Belgium.
AB  - : Emergency care in Belgium. Problems and objectives: Europe encompasses not only
      fifty or more different languages and cultures, but also a similar number of
      different systems of healthcare and medical practice. Each country has different
      medical traditions, different systems of professional registration and differing
      lists of medical specialties. METHODOLOGY: Literature, Report of The European
      Observatory on Health Systems, as well as World Health Organization health
      statistics analysis Results and conclusions: In this chapter, the Belgian
      healthcare system will be discussed, as well as the area of emergency medicine,
      which is currently recognized as an independent specialty. The different
      stakeholders in emergency medicine will also be discussed in this chapter, and
      their qualifications and responsibilities will be presented.

PMID- 29461732
TI  - First-line attitudes in acute medicine.
AB  - First-line attitudes in acute medicine. The often complex problems of the trauma
      and/or severely ill patient present many challenges to front-line emergency
      staff. Multiple injuries and/or systems of the body involved require careful and
      timely prioritization and intervention. Optimum evaluation and resuscitation
      involves repetitive, systematic ipproaches that are known as the "primary",
      "secondary" and "tertiary" surveys. The primary survey focuses in general on the
      ABCDE approach of "Airway, Breathing, Circulation, Disability, Expoure", and is
      designed to recognize and to treat immediate life-threatening conditions within
      the initial minutes. This primary resuscitation of non-trauma patients does not
      differ from the ABCDE approach used to evaluate severely traumatized patients.
      This approach is applicable in all clinical emergencies, whether the patient is
      located in the street, at home, in the emergency room, and even in the intensive
      care or the general wards of the hospital. This approach is widely accepted by
      experts, and is likely to improve outcomes by helping healthcare professionals to
      focus on the most life-threatening clinical problems. In an acute setting, high
      quality ABCDE skills among all treating team members can save valuable time and
      improve team performance. The secondary and the tertiary surveys are intended to
      diagnose all injuries before formulating definitive management strategies. This
      chapter briefly describes how to perform the ABCDE approach in general, and how
      to conduct the secondary and the tertiary surveys. A more detailed use of this
      approach within a specific medical condition will be described in later chapters
      of this report.

PMID- 29461733
TI  - Pre-hospital interventions: introduction to life support systems.
AB  - Pre-hospital interventions: introduction to life support systems. Crucial
      decisions in pre-hospital emergency care are often made; therefore, a tactical
      emergency medical support team (TEMS) should maintain the capacity to capture the
      situation instantaneously and in all circumstances. However, low exposure to
      severe trauma cases can be a weakness for emergency specialists, which makes pre
      hospital assessment more difficult. Pre-hospital interventions (PHI) are usually
      classified in Western countries into BLS (basic life support) and ALS (ad- vanced
      life support) levels, according to the methods used. This review introduces
      tactical combat casualty care for medical personnel (TCCC) guidelines, designed
      for basic care management under fire or in a hostile environment. The phases of
      TCCC are: (1) care under fire (or in an unstable environment); (2) tactical field
      care; and (3) tactical evacuation care, and are mainly dependent on the different
      hazard zones (hot, warm or cold). In a mass casualty situation due to disaster or
      cataclysm, standardized protocol and triage are unquestionably required for
      identifying the environmental risks, for categorizing the casualties in
      accordance with medical care priorities, and for the initial management of
      casualty care. When considering conflict situations, or chemical, biological,
      radiological, or nuclear (CBRN) events, processes always start at the local
      level. Even before the detection and analysis of agents can be undertaken,
      zoning, triage, decontamination, and treatment should be initiated promptly.
      Otorhinolaryngologists should be aware of PHI procedures for completing
      preliminary assessment and management together with emergency specialists or
      TEMS.

PMID- 29461734
TI  - Protection of respiratory integrity and haemodynamic stabilization.
AB  - : Protection of respiratory integrity and haemodynamic stabilization. OBJECTIVES:
      To perform an analysis of the protection of respiratory integrity and
      haemodynamic stabilization based on the literature review and the experiences and
      perspectives of emergency and ENT specialists. METHODOLOGY: A comprehensive
      literature search was undertaken through PubMed and MEDLINE, using the following
      keywords: [protection of the respiratory integrity], [intubation], [hypotension]
      and [haemodynamic stabilization]. Articles were selected if the topic was
      relevant to current ENT and emergency practice. Additional articles were
      identified through a careful review of reference lists in Uptodate. A critical
      review of ENT and emergency specialists was carried out. Evidence staging and
      recommendation levels were established using the Paul Shekelle scale. RESULTS:
      Firstly, protection of the airway is necessary before starting haemodynamic
      stabilization. Fibre-optic examination and laryngeal intubation form the gold
      standard of diagnosis and treatment in the protection of the airway. For
      circulation, a short catheter with a large size allows the management of
      intravenous fluids, with vasopressors if necessary. Aetiologic and specific
      treatments are also very important. CONCLUSIONS: Appropriate and collaborative
      management is necessary with the "ABCDE" approach: Airway and im- mobilization of
      the neck; Breathing; Circulation; Disability and Exposure. A fibre-optic
      examination is the gold standard of airway diagnosis. Laryngeal intubation is the
      most effective treatment for protection of the respiratory integrity. The
      management of circulation includes the implementation of a venous route to
      initiate administration of IVFs, preferably with isotonic saline. Vasopressors
      and inotropes are used as second line agents. A multidisciplinary and team
      approach is preferred, in order to achieve diagnosis and therapeutics
      simultaneously.

PMID- 29461735
TI  - Facing coagulation disorders after acute trauma.
AB  - : Facing coagulation disorders after acute trauma. PROBLEMS/OBJECTIVES: Trauma is
      the leading cause of mortality for persons between one and 44 years of age,
      essentially due to bleeding complications. METHODOLOGY: We screened the PubMed,
      Scopus and Cochrane Library databases, using specific keywords. Only publications
      in English were considered. MAIN RESULTS: The pathophysiology of trauma-induced
      coagulopathy (TIC) is complex and includes the classic "lethal triad" (i.e.,
      haemodilution, acidosis, hypothermia) but may also include activation of protein
      C, endothelial and platelet dysfunction, and fibrinogen depletion. The time
      between trauma and treatment of the resultant massive bleeding should be as short
      as possible using techniques for rapid control of bleeding and avoiding
      aggravating factors (hypothermia, metabolic acidosis and hypocalcaemia). If given
      within three hours of injury, tranexamic acid (TXA) reduces all causes of
      mortality in trauma patients and reduces transfusion requirements. In a bleeding
      patient, crystalloids are preferred to colloids and the ratio of fresh frozen
      plasma to packed red blood cells should be at least 1:2. Damage control surgery
      (DCS) should be considered for patients who present with, or are at risk for
      developing, the "lethal triad", multiple life-threatening injuries or shock, and
      in mass casualty situations. DCS can also aid in the evaluation of the extent of
      tissue injuries and the control of haemorrhage and infection. Finally, there is
      currently no evidence of the added value of laboratory assays in the management
      of TIC. CONCLUSIONS: TIC appears quickly after trauma and should be anticipated
      and detected as soon as possible. TXA plays a central role in the management of
      such patients. Each institution should establish a local algorithm for the
      management of bleeding patients.

PMID- 29461736
TI  - ENT indications for Hyperbaric Oxygen Therapy.
AB  - ENT indications for Hyperbaric Oxygen Therapy. Hyperbaric Oxygen (HBO) therapy is
      a treatment where patients breathe 100% oxygen while exposed to high
      environmental pressure in a hyperbaric chamber. This hyperoxygenation has several
      beneficial effects as an adjunctive treatment in a number of ENT-related
      conditions and diseases. These can be summarized as anti-ischaemic effects
      (delivery of oxygen to otherwise ischaemic tissues, reduction of ischaemia
      reperfusion damage), anti-infectious effects (bacteriostasis, improved leucocyte
      phagocytosis bactericidal activity and optimization of antibiotic therapy) and
      wound-healing effects (stimulation of granulation tissue formation and
      stabilization). Since HBO therapy has a clear physiologic rationale, a
      demonstrated effect (although difficult to "prove" with placebo controlled
      randomized trials) in certain indications and certain side-effects, it is
      proposed that it should be considered an integral part of the (combined surgical
      and pharmacological) treatment of patients, and not simply as a supplementation
      of oxygen. Furthermore, the importance of a well-trained medical and technical
      staff to ensure proper selection and the correct follow-up of patients should not
      be underestimated.

PMID- 29461737
TI  - Management of burn wounds of the head and neck region.
AB  - Management of burn wounds of the head and neck region. Management of the severely
      burned patient is ery often a challenge, not only due to major disturbances in
      anatomy and physiological processes, but also because the relatively low
      incidence of this pathology in both civilian and military practice results in
      care providers'lack of experience. The purpose of this educational document is to
      provide doctors confronted with these formidable trauma patients with basic
      management guidelines as well as some practical tips. In summary, and most
      importantly, these patients should be reated as any other multitrauma patient.
      First aid is essential and can be provided by non-medical staff. Initial medical
      nanagement should focus on the usual, familiar trauma algorithms of ABCDEF from
      the emergency management of evere burns (EMSB) manual' or the ABCDEs of the
      manual of advanced trauma life support (ATLS)2 or advanced burn life support
      (ABLS). Medical care should proceed through the following steps - Step one:
      establish a reliable intravenous nfusion; step two: protect the airway; step
      three: establish and maintain a haemodynamic state compatible with sufficient
      organ perfusion in order to reduce aggravation of the burn wounds and increase
      overall survival likelihood; step four: provide analgesia with adequate sedation
      and provide anaesthesia for escharotomy, fasciotomy or other surgical injuries;
      step five: maintain normothermia; step six: feed the patient by starting enteral
      nutrition as early as possible; step seven: prevent infection using antiseptic
      wound management, systemic antibiotics and tetanus prophylaxis. All of these
      intricate steps require continuous reassessment and adjustment, but the existence
      of other wounds (blast injuries, penetrating and blunt trauma) even further
      complicates the management of burn casualties.

PMID- 29461738
TI  - Toxic exposure to caustics and respiratory irritants.
AB  - Toxic exposure to caustics and respiratory irritants. Toxic emergencies for which
      the ENT physician is con- sulted mainly involve toxic exposure of the upper
      airway and digestive tract to caustics and respiratory irritants. The ENT
      physician may, however, also be involved as a first responder in the case of
      poisoned patients. This article therefore aims to provide a comprehensive general
      approach to patients with suspected poisoning and to present a more elaborate
      discussion on the diagnosis and management of patients following exposure to
      caustics and respiratory irritants. This survey, however, does not intend to be a
      substitute for the need for consultation with an emergency physician and a
      clinical toxicologist qualified in the diagnosis and treatment of poisoned
      patients.

PMID- 29461739
TI  - At risk populations: from children to the elderly.
AB  - : At risk populations:from children to the elderly. PROBLEMS/OBJECTIVES: When
      considering emergencies in children and elderly people, the risks and
      consequences are considerably different. For example, the anatomical differences
      of children have direct consequences on intubation and airway physiology
      influences breathing, circulation and neurological outcomes.Pharmacotherapy
      should be adapted for children according to their differences (maturational
      changes) where drug metabolism and disposition is concerned and for the elderly,
      to geriatric pharmacokinetics, pharmacodynamics, the existence of poly
      medications and the risk of adverse drug reactions. METHODOLOGY: Literature
      review Results: Children respond better to rapid medical care than adults.
      Hypoxia is dangerous for the child and is responsible for bradycardia and cardiac
      arrest. Hypoxia can be deleterious for elderly patients because of their
      fragility, e.g., less metabolic reserves, poor muscular compensation and higher
      risk of heart failure. CONCLUSIONS: It is widely accepted that children require
      paediatric-specific assessment/treatment equipment and pharmacotherapy. When
      compared to adults, there is no difference in the Royal College of Physician
      guidelines for elderly people's reanimation, however, other criteria such as
      polypathology, co-morbidity, polypharmacy, fragility, risk of delirium, adverse
      drug reaction, poor outcome and quality of life should be considered.

PMID- 29461740
TI  - Acute external ear lesions: clinical aspects, assessment and management.
AB  - Acute external ear lesions: clinical aspects, assessment and management. We
      reviewed the literature concerning the assessment and the management of the
      external ear traumas, which is not very rich. Nevertheless, we outlined the
      practical attitudes in the four major conditions met: the auricular haematoma,
      the auricular perichondritis, the auricular laceration and auricular bums. All
      these pathologies must be promptly treated because there is a risk of
      perichondritis, which can destroy the cartilage and will result in a severely
      deformed ear. Auricular haematomas must be drained as soon as possible,
      lacerations with exposed cartilage must be stitched urgently, and burnt ears
      should be washed, coated with alginates (Flaminal@) and covered with a loose
      dressing. Antibioprophyl- axy should always be prescribed after a complete
      microbiological sampling.

PMID- 29461741
TI  - Middle ear damages.
AB  - Middle ear damages. The eardrum and middle ear are often exposed to blunt and
      penetrating trauma, blasts, thermal or caustic injuries. These injuries may
      result in tympanic membrane perforation, middle ear haemorrhage, dislocation and
      fracture of the ossicular chain, perilymphatic fistula and damage to the chorda
      tympani and/or facial nerve. In case of life-threatening injuries and/or mass
      casualty incidents, middle ear trauma obviously does not take highest priority.
      However, middle ear lesions should be suspected and recognized as early as
      possible. After meticulous history taking, physical examination consists of
      cranial nerve evaluation, thorough inspection of the outer ear, otoscopy and
      assessment of hearing and vestibular function. In the majority of cases,
      traumatic tympanic membrane perforations by penetrating and blunt injuries have a
      good prognosis with spontaneous resolution. Tympanic membrane perforations from
      blast trauma, thermal or caustic injuries are less likely to heal spontaneously.
      Perforations lasting six months after injury warrant surgery. A high resolution
      CT scan of the temporal bone is required in case of immediate complete facial
      nerve paralysis and when oval window pathology or perilymphatic fistula is
      suspected. Early surgical intervention is needed in case of early onset facial
      nerve paralysis, when there is suspicion of a perilymphatic fistula with
      persisting or increasing vestibular symptoms or neurosensory hearing loss and in
      case of vestibular dislocation of the stapes footplate. When ossicular chain
      damage is suspected, elective tympanoplasty is indicated. As any traumatic
      tympanic membrane perforation runs the risk of cholesteatoma formation, biannual
      follow-up during a minimum of two years is recommended.

PMID- 29461742
TI  - Speech-in-noise testing as a marker for noise-induced hearing loss and tinnitus.
AB  - Speech-in-noise testing as a marker for noise-induced hearing loss and tinnitus.
      Noise-induced hearing loss and tinnitus are auditory complaints that often co
      occur. Often, there is no immediate indication of changes in the pure tone
      audiogram. Patients can still have clinically normal hearing thresholds while
      clearly experiencing reduced speech comprehension. This might be explained by the
      process of neurodegeneration of the innervated dendrites of the auditory nerve
      fibres and secondary degeneration of spiral ganglion neurons. Subsequent
      maladaptive neuronal plasticity of the central auditory system can induce
      tinnitus. Standard hearing testing is no longer sufficient in these patients.
      Therefore more complex tasks, such as speech-in-noise tests, might be valuable
      extensions to the standard hearing tests. We carried out a prospective
      investigation of the influence of tinnitus upon speech comprehension in noise and
      the effectiveness of speech-in-noise testing, using the Flemish version of the
      digit triplet test (DTT). Thirty-seven patients with mild noise-induced hearing
      loss, tinnitus complaints and clinically normal pure tone thresholds completed
      the DTT and filled in two tinnitus enquiries. A statistically significant
      (p=0.026) correlation between the averaged high PTA, 2,z and the averaged SRT
      across ears on the DTT was found. There also seems to be a slight influence of
      tinnitus onset on the SRT score.

PMID- 29461743
TI  - Basilar skull fractures: the petrous bone.
AB  - : Basilar skullfractures: the petrous bone. OBJECTIVES: to provide suggestions
      for the management of three of the most dangerous or important lesions (internal
      carotid artery lesions, cerebrospinal fluid leaks and facial nerve paralysis)
      associated with the petrous part of basilar skull fractures, thereby trying to
      assess categories of evidence and determine strengths of recommendation.
      METHODOLOGY: A PubMed-based literature review was carried out, as well as a
      consultation of online sources as encountered in the literature review. Also, a
      non-systematic search of chapters of well-known books dealing with the subject of
      temporal bone traumata was conducted. RESULTS: Specific levels of evidence and/or
      strength of recommendation can be retrieved from the literature, but only with
      respect to the prophylactic use of antibiotics, the prescription of
      antithrombotic medications and the indications for angiography. CONCLUSION: The
      ample amount of available literature allows for sound management decisions, with
      reference made to algorithms when available in the literature. Nevertheless, for
      most of the management/search questions, categories of evidence and strength of
      recommendation are low or lacking.

PMID- 29461744
TI  - Ear, nose and throat and non-acoustic barotrauma.
AB  - The organs of the ear, nose and throat (ENT) contain air- or gas-filled cavities,
      which make them sensitive to pressure changes. There is a specific
      pathophysiology involved when these structures are exposed to non-acoustic press
      ure changes, which are usually not traumatic in normals. The concepts of
      pathophysiology, diagnosis and treatment of these traumas in an emergency setting
      are reviewed.

PMID- 29461745
TI  - The Current Evidence on Retaining or Prosthodontically Replacing Retained
      Deciduous Teeth in the Adult Hypodontia Patient: A Systematic Review.
AB  - BACKGROUND: This systematic review aims to evaluate the survival of retaining or
      replacing deciduous teeth in hypodontia patients with a variety of prosthetic
      tooth replacement options, to evaluate prognostic factors associated with
      retaining deciduous teeth, and report on patient based outcomes with these
      treatment modalities. METHODS: MEDLINE, The Cochrane Central Register of
      Controlled Trials and Science Direct databases were searched (01/1980 - 08/2017)
      for studies reporting outcomes associated with retaining or replacing deciduous
      teeth via prosthetic means in adult hypodontia patients. RESULTS: Twenty-one
      articles were included. The following survival figures were reported; retaining
      deciduous tooth/teeth (83%-93%), resin-bonded bridgework (59-96.9%) and implants
      (86-100%). No survival data was reported for fixed or removable partial dentures.
      Prognostic factors for deciduous tooth survival, quality of life and patient
      satisfaction data were also reported. CONCLUSION: Within the limits of this
      review, retaining deciduous teeth have reasonable survival; however, studies
      beyond the third decade of life are lacking. Dental implants appear to be a
      highly successful long-term tooth replacement option with high patient
      satisfaction within this patient group, as have resin-bonded bridgework, albeit
      over the short to medium term. Tooth replacement options in the form of fixed and
      removable partial dentures were poorly reported upon.

PMID- 29461747
TI  - ?

PMID- 29461746
TI  - Marginal and Internal Gap of Handmade, Milled and 3D Printed Additive
      Manufactured Patterns for Pressed Lithium Disilicate Onlay Restorations.
AB  - STATEMENT OF THE PROBLEM: On a pressed lithium disilicate restoration, the
      building up of a wax pattern of the future restoration is a necessary step on the
      fabrication process. Conventionally, a wax pattern can be produced by handmade or
      milled procedures; however, the development of additive manufacturing
      technologies allows a new fabrication method. PURPOSE: The present study measured
      the marginal and internal gap of handmade, milled and additive manufactured
      patterns for an onlay restoration. MATERIAL AND METHODS: A preparation of an
      onlay restoration was made on an extracted mandibular tooth. A definitive cast
      was fabricated from a conventional silicone impression of the prepared tooth.
      Three groups were established: handmade (HM), milled (ML) and additive
      manufactured (AM); 4 specimens per group were obtained. The marginal and internal
      gap of each pattern was measured on the extracted molar through a computed
      tomography test. Sixty measurements were done to measure the marginal gap and
      another 60 measurements were calculated to analyze the internal gap on each
      pattern on the prepared tooth. A total of 1.440 measurements were completed. Mann
      Whitney and Turkey statistical tests were used for pairwise comparison. RESULTS:
      The mean of the marginal and internal gap was of 67.56 +/- 6.08 MUm and 80.62 +/-
      3.26 MUm for the HM group, 85.28 +/- 2.17 MUm and 96 +/- 1.97 MUm for the ML
      group and 86.49 +/- 1.74 MUm and 91.86 +/- 2.88 MUm for the AM group,
      respectively. The HM group presented significantly lower marginal (p=0.029) and
      internal (p=0.029) gap compared to the ML and AM groups. There was no statistical
      significant difference (p=0.486) on the marginal gap between the ML and the AM
      groups, but the AM group, showed significantly (p=0.029) smaller internal gap
      than the ML group. CONCLUSIONS: All the groups presented less than 100 MUm
      marginal and internal gap, which is a considered clinically acceptable. CLINICAL
      IMPLICATIONS: The three fabrication processes are viable option for manufacturing
      patterns for lithium disilicate onlay restorations, but the best marginal and
      internal fit was still obtained by the conventional handmade procedures.

PMID- 29461748
TI  - [Fever throughout the ages in children].
AB  - Fever is a common complaint in paediatric care and is mainly due to infectious
      causes. Depending on the age of the patient, clinical presentation will differ
      and the origins of the fever vary ; a good awareness of the age-related
      specificities is essential for early detection of invasive and potentially fatal
      infections. Fever may also be due to inflammatory diseases. A good knowledge of
      these aetiologies is essential to avoid unnecessary repeated antibiotic
      treatments and a lengthy misdiagnosis.

PMID- 29461749
TI  - [Persistant fevers of infectious origin in children].
AB  - Prolonged fevers in children are a regular challenge for the paediatrician or any
      physician caring for these children (emergency physicians, pediatric infectious
      diseases specialists). The causes are multiple, classified into three major
      families : infectious, inflammatory and oncological. Infectious causes are the
      most common and account for more than 50 % of cases. The objective of this review
      is to guide physicians in charge of these patients throughout their management by
      focusing on the quest of infectious causes.

PMID- 29461750
TI  - [Persistent fever in the travelling child].
AB  - Persistent fever or FUO (fever of unknown origin) is defined by a fever of more
      than 1-2 weeks that remains unexplained, after considerable diagnostic efforts.
      In the travelling child, in addition to cosmopolitan infectious diseases,
      tropical pathogens must absolutely be considered according to the regions visited
      and the activities practiced. A detailed history and a complete clinical
      examination are essential to decide which supplementary investigations will
      complete the basic assessment, which must contain the search for malaria in any
      child who has visited an endemic area. Following the diagnostic strategy proposed
      in this article, the clinician should be able to diagnose the most common
      diseases.

PMID- 29461751
TI  - [Systemic juvenile onset idiopathic arthritis and adult onset still disease].
AB  - Still's disease is a rare multifactorial disease associated with systemic
      inflammation. Systemic-onset juvenile idiopathic arthritis and adult-onset
      Still's disease are both pediatric and respectively adult forms of the disease
      with a cut-off age of 16 years. The disease is characterized by the following
      features : hectic fever > 39 degrees  C, arthralgia or arthritis, rash,
      neutrophilia and systemic inflammation. The prognosis of the disease is
      functional and vital. The evolution over time is variable : regression, evolution
      by relapses with regression at term and chronic joint evolution. This focus
      describes the two forms of the disease, their complications and the therapeutic
      options.

PMID- 29461752
TI  - [Recurrent auto-inflammatory fevers : a practical diagnostic flow chart].
AB  - Recurrent autoinflammatory fever syndromes are characterized by an abnormal
      activation of the innate immune system pathways, leading to inappropriate
      systemic inflammation responsible for clinical symptoms. The diagnosis of these
      conditions is difficult because of their low prevalence, but also because of
      their nonspecific clinical signs. The presence of clinical inflammatory signs
      such as fever associated to serositis (arthritis, peritonitis ...) or recurrent
      cutaneous manifestations and elevated acute phase reactants should help the
      clinician to make the correct diagnosis. The purpose of this article is to
      provide a practical management flow chart for children with a suspected
      autoinflammatory recurrent fever syndrome.

PMID- 29461753
TI  - [Kawasaki disease: an update].
AB  - The cause of Kawasaki disease (KD) is still unknown, but an infectious origin and
      genetic susceptibility have been suggested. The American Heart Association has
      changed the guidelines for diagnosis and treatment of KD in 2017. One goal is to
      better identify patients most at risk, particularly young children with "
      incomplete " KD. In case of intravenous immunoglobulin resistance, alternative
      treatments to the traditional use of corticosteroids, such as TNF-alpha
      inhibitors have been proposed. For all patients with coronary aneurisms, regular
      assessment of myocardial perfusion is recommended, either with stress
      echocardiography, MRI, scintigraphy or PET-scan.

PMID- 29461754
TI  - ?

PMID- 29461755
TI  - ?

PMID- 29461756
TI  - ?

PMID- 29461757
TI  - ?

PMID- 29461758
TI  - ?

PMID- 29461759
TI  - ?

PMID- 29461760
TI  - ?

PMID- 29461761
TI  - ?

PMID- 29461762
TI  - [Changes in mangrove coverage in Culebra Bay, North Pacific of Costa Rica (1945
      2010)].
AB  - Despite the economic and environmental services that mangroves provide, they
      continue to be threatened by overexploitation, pollution, and land use change.
      Costa Rica has mangrove areas on the Pacific and Caribbean coasts, and cover has
      been declining since the 1980s. However, data on mangrove coverage are not
      continually updated and are often based on inaccurate estimates. It is therefore
      necessary to assess the current extension and variation of the mangrove cover in
      recent years, to determine changes. The mangrove cover was analyzed in two
      mangrove forests located in Bahia Culebra, North Pacific: Iguanita and Playa
      Panama. For this, aerial photographs and satellite imagery were used to study
      changes for a 65 year period (1945-2010). Spatio-temporal changes were found in
      mangroves coverage, and adjacent forests and areas without vegetation. Lower
      mangrove cover occurred during the 1970s (28.4 ha in Iguanita and 4.8 ha in Playa
      Panama); but increased in recent years (38.9 ha in Iguanita and 12.0 ha in
      Panama). Changes in forest cover by the Iguanita and Playa Panama mangroves were
      related to the history of land use around Bahia Culebra. Before 1980, there was
      extensive and intensive cattle ranching, increasing the deforestation rate; after
      that year, these practices were abandoned and secondary forest coverage increased
      until 2000. To ensure the adequate protection of mangroves, it is not only
      important to protect mangrove forests, but it is also necessary to establish
      buffer zones on their surroundings, to mitigate and/or reduce possible impacts.

PMID- 29461763
TI  - Seed dormancy of Ochradenus baccatus (Resedaceae), a shrubby species from Arabian
      desert regions.
AB  - Ochradenus baccatus is a perennial glycophyte growing in Middle East and it is
      one of the most important food sources for many animal species in desert regions.
      The aim of our study was to investigate the effects of seed storage, light,
      temperature and gibberellic acid (GA3) on germination of O. baccatus seeds. We
      also investigated the germination characteristics of O. baccatus seeds under
      different saline concentration and their capability to recover germination once
      they were transferred to distilled water. Seeds were stored at room temperature
      (20 +/- 2 oC) and at -18 oC. Germination tests were conducted at alternating
      temperatures of 15/25, 20/30 and 25/35 oC in either continuous darkness or
      photoperiod of 12-h dark/12-h light. To study the effect of GA3 on germination of
      O. baccatus seeds, freshly-collected seeds and stored seeds were soaked for 24 h
      in a GA3 water solution (1 g/L) before sowing. To assess the salinity tolerance
      during germination, seeds were germinated under different salinity levels (100,
      200 and 400 mM NaCl). Stored seeds at room temperature and -18 oC germinate
      equally well at different temperature regimes and light conditions. However,
      freshly matured seeds were not able to germinate even when they were treated with
      GA3. On the contrary, stored seeds at room temperature and -18 oC treated with
      GA3 increase the final germination percentages. These results indicated that O.
      baccatus seeds have physiological dormancy and they need to be stored in order to
      break their dormancy. In the present study, one year of storage did not show a
      significant variation in germination between the two storage conditions assayed.
      Therefore, further research is needed to know about the maximum storage period
      for O. baccatus seeds under different storage conditions. Very few O. baccatus
      seeds (less than 5 %) germinated at the tested lowest concentration of NaCl.
      However, ungerminated seeds were able to germinate when salinity stress was
      alleviated. In conclusion, O. baccatus seeds have physiological dormancy, and
      seed storage (at room temperature and at -18 oC) for one year is effective for
      breaking this dormancy. In addition, O. baccatus seeds present ability to remain
      viable in saline conditions and they will be able to germinate once the salinity
      level decrease.

PMID- 29461764
TI  - [Phenotypic variation of Panulirus argus (Decapoda: Paniluridae) in Southwest
      Caribbean].
AB  - The spiny lobster Panulirus argus is an important fishery species in the Western
      Central Atlantic. Changes in the dispersion range through its life cycle and
      heterogeneous habitats, suggest that P. argus exhibit phenotypic plasticity.
      However, the morphometric variation of this species is unknown so far, although
      this information is relevant in evolutionary studies as well as to solve
      questions of fishery interest. Thus, the aim of this study was to determine
      whether P. argus exhibit phenotypic variation between sexes, among five
      geographic origins and three oceanographic conditions of Southwest Caribbean
      (Colombian archipelago San Andres, Providencia y Santa Catalina). A total of 193
      P. argus adults were submitted to geometric morphometrics using six landmarks
      that delimit one half of the sternal plate. The differences in sternal plate size
      were compared with Kruskal-Wallis and Mann-Whitney Tests. The allometric effect
      was estimated using Multivariate Regression Analysis, the model of allometric
      slopes was tested by Multivariate analysis of covariance and the sternal plate
      shape differences was explored using non-parametric comparisons of Euclidian
      distances and Neighbour Joinnig trees. The results showed that the morphometric
      variation of sternal plate of this spiny lobster varied according to the gender
      since the sexual size and shape dimorphisms were significant. In both sexes, the
      sternal plate shape differed among oceanographic scenarios as it was evidenced by
      significant differences among Euclidian distances, and the tendency to cluster by
      North, Centre and South sections of San Andres archipelago. Additionally, the
      morphometric variation resulting from phenotypic plasticity to variable
      ecological contexts may explain the phenotypic differences among genetically
      similar populations. This information permits to define management units, support
      the selection of regulatory policies of this fishery and complement the genetic
      analysis of the species in this Caribbean region.

PMID- 29461765
TI  - [Spontaneous spawning, ontogeny and growth in captivity of Cynoscion squamipinnis
      (Perciformes: Sciaenidae)].
AB  - The croakers or drums are commercial species, which have been overfished in the
      Nicoya Gulf, Costa Rica. This study aimed to describe, for the first time, the
      reproduction and the ontogeny of weakfish, Cynoscion squamipinnis in captivity,
      in order to perform restocking and mariculture proyects. Wild fish (n= 6, 1-2 Kg)
      were captured and maintained in the Estacion de Biologia Marina Juan Bertoglia
      Richards (Puntarenas, Costa Rica) for a two years period (October 2006- December
      2008). During this period, maturation stage was monitored periodically by cannula
      samples in the females (n= 3) and gentle massage in males (n= 3). All fish were
      stocked in an 18 t tank, with aeration, 33-35 ups of salinity, and a constant
      temperature (29 +/- 1  degrees C). The spawning period occurred from January to
      March 2009, producing 162 000 eggs in three spontaneous spawns. The fertilization
      percentage was 50-60%, and survival after hatching was 60-85%. The egg diameter
      was 0.852 mm (Standard deviation (SD)= 0.039), and oil drop of 0.269 mm (SD=
      0.016). In the embryonary development, the first mitotic division (MD) was
      observed one hour after spawning (has), the second MD was 1:30 has, the third MD
      was 2:00 has, the fourth MD was 2:30 has, and fifth MD at 3:00 has. Morule was
      observed 3:30 has, the blastule 4:30 has, the gastrule 8:30 has, C shape at 10:00
      has, and C shape at 12:00 has. After 19 has hatching larvae occurred. The total
      length (TL) of the larvae was 2.234 mm (SD= 0.122), and the nothochordial length
      (NL) was 2.179 mm (SD= 0.119). Preflexion stage was observed 49 has, flexion
      stage was 11 days after spawn (das) (3.767 mm LT (SD= 0.209)), and postflexion
      stage was 14 das (4.015 mm LT (SD= 0.302)). After 45 das, the juvenile weights
      3.68 g (SD= 1.09). Hatch time of the weakfish larvae was minor than of others
      croaker species. The stages times of embrionary development were a little
      different from others croaker species, and probably respond to genetic
      characteristics of each species and the eggs incubation temperature. The
      spontaneously spawning without broodstock hormonal applications, and the
      juveniles production in captivity showed that weakfish is a potential species for
      restocking programs and mariculture projects.

PMID- 29461766
TI  - [Anatomical changes in roots and hypocotyls of Prosopis ruscifolia (Fabaceae)
      seedlings exposed to saline stress].
AB  - Prosopis ruscifolia is a pioneer tree species in flooding or saline areas. The
      aim of this work was to assess anatomical changes in roots and hypocotyls of P.
      ruscifolia seedlings induced to saline stress under controlled conditions. Seeds,
      collected in natural forests of Western Chaco region in Argentina, were sown on
      paper towels moisturized with saline solutions of 100, 200 and 300 mM of NaCl,
      and a control group with distilled water. Four repetitions of 50 seeds per
      treatment were sown, located in hermetic polystyrene boxes, and included in a
      seeding chamber, at 27 oC and 12 hours photoperiod. Were studied 35 seedlings
      from each saline concentration; these seedlings were processed 12 days after sown
      to obtain microscopic samples. The anatomical variables measured in roots and
      hypocotyls were the following: main root diameter (um), bark thickness (um),
      number of cell strata in bark, central cylinder diameter (um), pith diameter
      (um), number of cell strata in the pericycle and the tangential diameter of
      vessels (um). ANOVA analysis were performed with hypocotyl and root diameters as
      the dependent variable, and bark thickness (um), number of cell strata in the
      bark, the central cylinder diameter (um), the pith diameter (um), number of cell
      strata in the pericycle, the tangential diameter of vessels and the saline
      concentration as independent variables. Results showed that the root diameter
      decreased with increasing saline concentrations (P < 0.0001). The bark thickness
      decreased at 100 mM (P < 0.0001) and the number of cell strata of bark increased
      to 300 mM (P < 0.0002). The central cylinder diameter decreased at 100 mM saline
      concentration (P < 0.0001) and the number of cell strata of the pericycle and the
      pith diameter reduced progressively until 300 mM. The tangential diameter of
      vessels decreased at 300 mM. These anatomical changes suggested alterations in
      the expansion and cell division caused by the salinity, and could limit lateral
      roots formation and reserves storage. Hypocotyls did not show significant
      anatomical changes in response to increasing salinity, with exception of stomata
      position and an increase of the hypodermis thickness. These changes indicated
      that the water stress imposed by low osmotic potential is caused by increasing
      saline concentration. The seedlings of P. ruscifolia experienced anatomical
      changes in response to tested saline concentrations in traits related to reserve
      storage, the absorption and conduction of water, and lateral roots formation.

PMID- 29461767
TI  - Scorpions maintenance in captivity for venom extraction purposes in Costa Rica.
AB  - Approximately 2 000 scorpion species can be found around the world; although few
      species are considered "harmful" to human beings, a high number of scorpionism
      cases are reported all over the world. The elaboration of anti-scorpion sera
      requires the establishment of an animal collection maintained in captivity for
      venom extraction purposes. The Clodomiro Picado Institute (ICP, for its acronym
      in Spanish), poses a vast trajectory in manufacturing snakebite antivenoms, and
      starts a scorpion collection in 2005 for this purpose. In total, 2 043 scorpions
      were classified in 11 species and collected during a seven-year period using a
      black-light flashlight and an intensive seeking methodology. The scorpions were
      collected from several localities of the Pacific and the Caribbean versants of
      Costa Rica. The venom extraction was performed by applying electrostimulation;
      the collected venom was characterized by total protein content in addition to
      median lethal doses. Centruroides bicolor showed higher amounts of venom yield,
      total protein content and more lethal dose, all of which were correlated with its
      body mass. The techniques used to keep scorpions in captivity allowed the animals
      to live several years. Longevity analysis showed significant differences among
      scorpion genera (H= 353.80; df= 3; P < 0.0001); moreover, the genus Didymocentrus
      lived longer with an average of 4.46 years. One key factor of its longevity was
      that it did not go through venom extraction processes. Additionally, a high
      survival rate of Tityus pachyurus born in captivity, compared to other species
      within the same genus, was observed (H= 94.32; df= 3; P < 0.0001). This
      characteristic should be taken into consideration, when programs of reproduction
      in captivity are designed. In conclusion, the maintenance of a scorpion
      collection was efficient for venom extraction purposes and a longer life
      expectancy of the animals. Moreover, there is a scarcity on publications
      regarding scorpion maintenance in captivity for venom extraction purposes;
      therefore, a deeper research in aspects such as reproduction, death causes and
      feeding behaviors is required.

PMID- 29461768
TI  - Changes in abundance and composition of a Caribbean coral reef zooplankton
      community after 25 years.
AB  - Coral reef zooplankton represents a key community in coral ecosystems, as they
      are involved in trophic and biogeochemical dynamics, and recruitment processes.
      Zooplankton abundance, composition and biomass were surveyed at six stations
      within the coral reef at Cahuita National Park, Limon, Costa Rica, in order to
      compare with the only previous study conducted during 1984. Samples were
      collected monthly (September 2010-August 2011). Seston biomass (0.49-85.87 mg/m3)
      and total abundance (1 145-112 422 ind./m3) fluctuated among the months and the
      stations. Higher values of these two variables were found in the rainiest months
      (November 2010 and May 2011). A total of 38 taxa were identified, of which
      calanoid copepods abundance dominated year round (66 %), followed by
      appendicularians (12 %). Zooplankton mean abundance in this survey resulted 20
      times higher (13 184 +/- 4 104 ind./m3)than in 1984 (645 +/- 84 ind./m3).
      Copepods and appendicularians were the groups that differed the most, relative to
      the 1984 study, resulting in 63 and 170 times more abundant overall,
      respectively. An increase in terrestrial runoff and nutrient input during the
      past 30 years could explain these differences. High abundances of zooplankton may
      constitute an important food source for coral reef organisms in Cahuita
      ecosystem. In addition, zooplankton abundances here reported for Cahuita are
      among the worldwide highest coral reef zooplankton abundances, and further
      trophic models can help elucidate its role in coral reef resilience in the
      Caribbean Coast of Central America.

PMID- 29461769
TI  - Nesting habits of Centris (Hemisiella) dichrootricha (Hymenoptera: Apidae) in the
      Northern Cerrado of Brazil.
AB  - The Neotropical bee Centris (Hemisiella) dichrootricha is a solitary bee that
      nests in pre-existing cavities that occur in the rain forest. This study
      describes the nesting biology of C. dichrootricha and its preference for nesting
      in Cerrado and gallery forest habitats. The study was conducted from January 2012
      and December 2013, in Mirador State Park in the municipality of Formosa da Serra
      Negra, Maranhao State, Brazil. For this, wooden trap-nests of 6, 8, 10, 12, 14
      and 16 mm in diameter were used; a total of 300 trap-nests were placed in the
      gallery forest and Cerrado areas, respectively. Traps were monitored monthly and
      all completed nests were collected and replaced with empty ones. The nests were
      then taken to the laboratory to analyze bee development and emergence, nests
      characteristics and parasites presence. The species used 29 of the trap-nests,
      which had diameters of 8, 10, 12 and 14 mm. A total of 87 C. dichrootricha
      specimens emerged. The nests were parasitized by two bee species, Mesocheira
      bicolor (Apinae) and Coelioxys sp. (Megachilinae), and one fly species, Antrax
      sp. (Diptera). The highest nesting incidence of 72.4 % was observed in the
      gallery forest, whereas only 27.6 % in the Cerrado; this difference in habitat
      use was significant (chi2 = 5.56; p < 0.05; DF = 1). For the nests that were
      built in the gallery forest, 80.9% of the soil originated from the Cerrado. The
      females were significantly larger than the males (F1, 76 = 595.19; p < 0.001).
      There were 11 pollen types that belonged to six families. Pollen of the family
      Malpighiaceae was most frequently used, with four species represented (Byrsonima
      crassifolia, B. rotunda, B. spicata and Heteropterys sp.). C. dichrootricha
      showed a preference for nesting in cavities of various diameters in gallery
      forest sites. The present study provides a novel description of the nesting
      habits and biology of C. dichrootricha in habitats of Central/Southern Maranhao.
      C. dichrootricha primarily used resources from the Cerrado, including soil to
      build their nests, pollen and floral oils; we concluded that gallery forest and
      Cerrado areas are intrinsically related to the maintenance of local populations
      of this species.

PMID- 29461770
TI  - Habitat conditions drive phylogenetic structure of dominant bacterial phyla of
      microbialite communities from different locations in Mexico.
AB  - Community structure and composition are dictated by evolutionary and ecological
      assembly processes which are manifested in signals of, species diversity, species
      abundance and species relatedness. Analysis of species coexisting relatedness,
      has received attention as a tool to identify the processes that influence the
      composition of a community within a particular habitat. In this study, we tested
      if microbialite genetic composition is dependent on random events versus
      biological/abiotical factors. This study was based on a large genetic data set of
      two hypervariable regions (V5 and V6) from previously generated barcoded 16S rRNA
      amplicons from nine microbialite communities distributed in Northeastern, Central
      and Southeastern Mexico collected in May and June of 2009. Genetic data of the
      most abundant phyla (Proteobacteria, Planctomycetes, Verrucomicrobia,
      Bacteroidetes, and Cyanobacteria) were investigated in order to state the
      phylogenetic structure of the complete communities as well as each phylum. For
      the complete dataset, Webb NTI index showed positive and significant values in
      the nine communities analysed, where values ranged from 31.5 in Pozas Azules I to
      57.2 in Bacalar Pirate Channel; meanwhile, NRI index were positive and
      significant in six of the nine communities analysed with values ranging from 18.1
      in Pozas Azules I to 45.1 in Rio Mesquites. On the other hand, when comparing
      each individual phylum, NTI index were positive and significant in all groups,
      except in Cyanobacteria for which positive and significant values were only found
      in three localities; finally, NRI index was significant in only a few of the
      comparisons performed. The results suggest that habitat filtering is the main
      process that drives phylogenetic structure in bacterial communities associated to
      microbialites with the exception of Cyanobacteria where different lineages can
      contribute to microbialite formation and growth.

PMID- 29461783
TI  - Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes
      CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population.
AB  - CYP2C9, CYP2C19 and CYP2D6 metabolize around 40% of drugs and their genes vary
      across populations. The Costa Rican population has a trihybrid ancestry and its
      key geographic location turns it into a suitable scenario to evaluate interethnic
      differences across populations. This study aims to describe the diversity of
      CYP2C9, CYP2C19 and CYP2D6 polymorphisms in Costa Rican populations in the
      context of their ancestry. A total of 448 healthy individuals were included in
      the study: Bribri (n= 47), Cabecar (n= 27), Maleku (n= 16), Guaymi (n= 30),
      Huetar (n= 48), Chorotega (n= 41), Admixed/Mestizos from the Central
      Valley/Guanacaste (n= 189), and Afro-Caribbeans (n= 50) from Limon. CYP2C9
      (alleles *2, *3, *6) and CYP2C19 (*2, *3, *4, *5, *17) genotypes were determined
      by Real-Time PCR. African, European and Native American ancestry were inferred
      using 87 ancestry informative markers. The frequency of the decreased activity
      allele CYP2C9*2 is lower in the self-reported Amerindian groups compared to the
      admixed population, and the highest frequencies of CYP2C19*2 (null activity) and
      the CYP2C19*17 (increased activity) were found in the self-reported Afro
      Caribbean population. Moreover, a frequency of 0.7 % CYP2C9 gPMs in the Admixed
      population and a variable frequency of CYP2C19 gUMs (0.0-32.6 %, more prevalent
      in Afro-Caribbeans) in Costa Rican populations, was found. Finally, the following
      alleles were positively correlated with genomic African ancestry and negatively
      correlated with genomic Native American ancestry: CYP2D6*5 (null activity),
      CYP2D6*17 (decreased activity), CYP2D6*29 (decreased activity) and CYP2C19*17
      (increased activity). No correlation for CYP2C9 polymorphisms and genomic
      ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in
      these populations, preferentially by sequencing these genes, are warranted.

PMID- 29461784
TI  - [Influence of sediments and tungsten traces on the skeletal structure of
      Pseudodiploria: a reef building scleractinian coral from the Veracruz Reef System
      National Park, Mexico].
AB  - Coral reefs are under intense conditions of stress caused by the anthropogenic
      activities in coastalareas and the increase of human population. Water effluents
      from urban and industrial areas carry large amountsof sediments and pollutants
      affecting corals populations, inducing bioerosion, increasing diseases and
      promotingthe development of algae that compete for space with corals. In the
      Veracruz Reef System National Park(VRSNP) coral reefs are strongly affected by
      human activities carried out in the area. Gallega and Galleguillareefs are among
      the most affected by wastewater discharges from the industrial (petrochemical and
      metallurgical)and urban areas in their vicinity. To assess the potential impact
      of this contamination on corals inthe VRSNP, a chemical composition and
      morphology study of 76 Pseudodiploria colonies collected in reefsGallega,
      Galleguilla, Isla Verde and Isla de Enmedio, was performed. Fragments of ~10 cm2
      were collected andboric acid at 0.5 % was used to remove tissue from the
      skeleton; once clean, the morphology of each samplewas determined with a scanning
      electron microscope (SEM). Subsequently, to test the chemical composition,
      anenergy dispersion spectroscopy of X-ray chemical microanalysis (EDSX) was
      performed in the SEM. We foundthat corals from Gallega and Galleguilla reefs,
      located closer to human populations, presented high levels oftungsten and the
      skeleton exhibited multiple perforations. In contrast, corals from the farthest
      offshore reefs (IslaVerde and Isla de Enmedio) exhibited lower levels of tungsten
      and fewer perforations in their skeleton. Theseresults demonstrated that
      anthropogenic activities in the NPVRS are affecting corals skeleton, highly
      damagingand promoting their bioerosion. The presence of traces of tungsten in the
      skeleton of corals is an evidence of thedamage that waste discharges are causing
      to coral reefs. Discharges of large amounts of contaminants promotedthe growth of
      harmful species that grow and develop into the corals skeleton, causing its
      bioerosion, and makingthem susceptible to disease and physical damage. This study
      is the first evidence of the effects of contaminationon these species; therefore,
      further studies are necessary to determine the impact of pollution on their
      biologyand survival.

PMID- 29461785
TI  - Diversity and spatial genetic structure of a natural population of Theobroma
      speciosum (Malvaceae) in the Brazilian Amazon.
AB  - The quantification of genetic diversity and intrapopulation spatial genetic
      structure (SGS) of tree species are important aspects for in and ex situ
      conservation practices. In this study we seek to understand the importance of
      conservation areas by quantifying the genetic diversity and the spatial genetic
      structure of a natural population of Theobroma speciosum. Within this population,
      49 adults and 51 subadults were genotyped for five microsatellite loci. The
      results showed that adults and subadults have similar levels of genetic diversity
      and inbreeding (adults: A= 10.4, Ae = 10.3, F= 0.68, subadults: A= 10.6, Ae=
      10.6, F= 0.57). Genetic diversity was spatially structured within the population,
      and the results suggest that near-neighbor trees up to a distance of 70 m are
      likely related. SGS is likely the result of short-distance seed dispersal, the
      short-distance range of pollinators, and infrequent breaches of the self
      incompatible mating system. Considering the high demographic density of the
      species and size of the study area, as well as the high average number of alleles
      per locus and the presence of rare alleles, we believe that the study population
      is an excellent resource for in situ genetic conservation of T. speciosum. The
      study area is also a useful resource for collecting germplasm for ex situ
      conservation and seed collection, either for breeding programs used in the
      restoration of degraded areas or forest improvement.

PMID- 29461786
TI  - Volatile compounds profile of Bromeliaceae flowers.
AB  - Volatile compounds play a vital role in the life cycle of plants, possessing
      antimicrobial and anti-herbivore activities, and with a significant importance in
      the food, cosmetic, chemical, and pharmaceutical industry. This study aimed to
      identify the volatile compounds emitted by flowers of thirteen species belonging
      to four genera of Bromeliaceae, using headspace solid-phase micro-extraction and
      detection by gas chromatography-mass spectrometry. A total of 71 volatile
      compounds belonging to nine chemical groups were identified. The compounds
      identified represented more than 97 % of the major components in Aechmea bicolor,
      Ae. bromeliifolia, Ae. distichantha, Ae. fasciata, and Vriesea friburgensis. In
      the Ananas varieties, over 99 % of the components were identified, and around 90
      % in V. simplex. V. friburgensis presented the largest diversity of volatiles
      with 31 compounds, while Alcantarea nahoumii presented only 14. All three Ananas
      varieties presented the same 28 compounds in relatively similar abundance, which
      has been confirmed by principal component analysis. Current taxonomy and
      pollination syndrome studies available can adequately explain the variation in
      volatile compounds among species.

PMID- 29461787
TI  - Caryocar coriaceum (Caryocaraceae) diaspore removal and dispersal distance on the
      margin and in the interior of a Cerrado area in Northeastern Brazil.
AB  - The seed dispersal process is a crucial stage in plant regeneration and
      maintenance of forest biological diversity. While the number of removed seeds is
      quantitative, the distance to which a seed is removed from its origin is
      qualitative, because it affects the probability that a seed will germinate and
      recruit to the next life stage. However, the creation of forest margins can
      negatively affect the seed dispersal process, especially for large-diaspore plant
      species. In this study, the diaspore removal and dispersal distance of Caryocar
      coriaceum, a tree with large diaspores that is in danger of extinction, were
      analyzed. The study was conducted for two consecutive years in a protected forest
      in Northeastern Brazil. Each year, 1 200 diaspores with a nylon wire and a satin
      tape yellow were used and equally distributed in 120 experimental stations
      established on the forest margin and in the interior. During the first year of
      the study, no differences in diaspore removal and dispersal distance were found
      among the investigated environments. However, for the second year of the study,
      the number of removed diaspores differed significantly; nevertheless, the
      dispersal distance was not different between the forest margin and the interior.
      The low diaspore removal percentages suggest that species recruitment may be
      compromised because the diaspore accumulation close to the relatives enables
      higher fungi and insect attack. In addition, most of the few removed diaspores
      were found at short distances from their sources (up to 5 m), which can lead to
      low genetic variability. Virtually no diaspore was found buried by hoarding
      rodents, and no diaspore was found preyed upon by these animals. Evidence found
      in this study suggests the local loss of species dispersers, which can compromise
      the maintenance of forest biological diversity.

PMID- 29461788
TI  - Impact of fishing with Tephrosia candida (Fabaceae) on diversity and abundance of
      fish in the streams at the boundary of Sinharaja Man and Biosphere Forest
      Reserve, Sri Lanka.
AB  - Local communities in some Asian, African and American countries, use plant toxins
      in fish poisoning for fishing activities; however, the effects of this practice
      on the particular wild fish assemblages is unknown. This study was conducted with
      the aim to investigate the effects of fish poisoning using Tephrosia candida, on
      freshwater fish diversity and abundance in streams at the boundary of the World
      Natural Heritage site, Sinharaja Forest Reserve, Sri Lanka. A total of seven
      field trips were undertaken on a bimonthly basis, from May 2013 to June 2014. We
      surveyed five streams with similar environmental and climatological conditions at
      the boundary of Sinharaja forest. We selected three streams with active fish
      poisoning practices as treatments, and two streams with no fish poisoning as
      controls. Physico-chemical parameters and flow rate of water in selected streams
      were also measured at bimonthly intervals. Fish were sampled by electrofishing
      and nets in three randomly selected confined locations (6 x 2 m stretch) along
      every stream. Fish species were identified, their abundances were recorded, and
      Shannon-Weiner diversity index was calculated for each stream. Streams were
      clustered based on the Bray-Curtis similarity matrix for fish composition and
      abundance. Physico-chemical parameters of water were not significantly different
      among streams (P > 0.05). A total of 15 fish species belonging to four different
      orders Cypriniformes, Cyprinodontiformes, Perciformes and Siluriformes were
      collected; nine species (60 %) were endemic, and six (40 %) were native species.
      From these, 13 fish species were recorded in streams with no poisoning, while
      five species were recorded in streams where poisoning was practiced. Four endemic
      and one native fish species were locally extinct in streams where fish poisoning
      was active. Fish abundance was significantly higher in control streams (32-39/m2)
      when compared to treatment streams (5-9/m2) (P < 0.05). We concluded that fish
      poisoning with T. candida may have resulted in a significant reduction in species
      richness, total abundance and Shannon-Weiner diversity index of fish species in
      the studied streams at the boundary of Sinharaja forest. We recommend that this
      fishing practice should be strictly regulated, and to inform local communities
      about the legal status of fish poisoning, its consequences and the importance of
      fish diversity for local livelihoods and conservation purposes.

PMID- 29461789
TI  - Biomass allocation and gas exchange are affected by light conditions in
      endangered Cedrela salvadorensis (Meliaceae) seedlings.
AB  - The determination of favorable light habitat conditions per species and life
      stage is transcendental, for both ex situ and in situ conservation strategies of
      endangered forest tree species, and for their utilization as plantation trees.
      This becomes especially important when planting material is scarce. We studied
      the multivariate responses in biomass allocation and in gas exchange to light and
      to CO2 in Cedrela salvadorensis seedlings, grown under similar light conditions
      as those this species faces in nature. During a period of 135 days, groups of ten
      seedlings were put under 75, 45, 15 and 3.5 % of full sun exposure obtained with
      neutral shade cloth, under nursery conditions. A series of biomass allocation
      variables and detailed gas exchange parameters (photosynthesis response curves to
      light and to internal carbon concentration) were measured at the end of the
      growth period in plants of the four treatments. According to the principal
      component analyses, highest values of gas exchange response were associated with
      the lower values of biomass allocation traits. These changes can be associated
      with resource-conservative and resource-acquisitive strategies, where the C.
      salvadorensis seedlings acclimatize their traits for the exploration and
      exploitation of light, to high or to dim light environment, respectively. The
      multivariate analyses also showed that the plants had a high performance at 45 %
      of light environment. These results suggest that 45 % of light environment was
      the optimal light habitat of this species at the tested developing stage. Our
      results have important implications to choose the best natural habitat for a
      successful establishment of C. salvadorensis. We propose practical considerations
      for programs of reforestation or reintroduction where this species be involved.

PMID- 29461790
TI  - Cranial osteology of the genus Sclerurus (Passeriformes: Furnariidae).
AB  - The Furnariidae encompasses 293 species and has been recognized as an example of
      continental adaptive radiation. They inhabit biomes from deserts to humid forests
      at all strata and show morphological heterogeneity unparalleled among birds at
      any taxonomic level. Sclerurus is a uniform genus of cryptic, mainly dark brown
      furnariids, with short black tails which are found solitary on or near the ground
      inside humid forest. The aim of the present study was to describe and to compare
      the cranial osteology of all six Sclerurus species (S. scansor, S. mexicanus, S.
      guatemalensis, S. caudacutus, S. rufigularis, and S. albigularis) to identify
      osteological characters that are (1) unique to each species, (2) shared among
      species, and (3) that are exclusive to the genus when compared to other members
      of Furnariidae. For this, bone structures and measurements were done following
      standard methodologies. The results showed that Sclerurus differs from other
      Furnariidae in the following characteristics: a narrowed caudal portion of the
      nostril with a more rounded shape allowing upper's jaw greater mobility, used
      when foraging on soft substrates; the development of the post-orbital process may
      be related to digging behavior, as the presence of a short parsphenoid rostrum
      projection, a reduced cerebellar prominence, and the tapered caudal portion of
      the nostrils. Among the species, the interorbital width is larger in S.
      caudacutus and S. rufigularis, than in the remaining species. The development of
      the post-orbital process may be related to the behavior of digging nests in
      earthen banks; the narrowing of the caudal portion of the nostril allows for the
      greater mobility of the superior maxilla, which is used by Sclerurus when
      foraging in soft substrates on forest grounds.

PMID- 29461791
TI  - [Concentrations of alkaloids, cyanogenic glycosides, polyphenols and saponins in
      selected medicinal plants from Ecuador and their relationship with acute toxicity
      against Artemia salina].
AB  - Alkaloids, polyphenols, cyanogenic glycosides and saponins are among the main
      chemical compounds synthesized by plants but not considered essential for their
      basic metabolism. These compounds have different functions in plants, and have
      been recognized with medicinal and pharmacological properties. In this research,
      concentrations of the mentioned secondary metabolites were determined in the
      medicinal plants Artemisia absinthium, Cnidoscolus aconitifolius, Parthenium
      hysterophorus, Piper carpunya and Taraxacum officinale, from Ecuador, and related
      with cytotoxic effects against Artemia salina. Alcoholic and aqueous extracts
      from leaves of these selected plants were prepared at different concentrations.
      To assess cytotoxicity of these extracts, different bioassays with A. salina were
      undertaken, and the mortality rates and LC50 were obtained. Besides,
      concentrations of alkaloids, cyanogenic glycosides, phenols, tannins and saponins
      were determined by spectrophotometric methods; this constituted the first report
      of quantification of secondary metabolites in the selected plants from Ecuador.
      T. officinale had the highest concentration of total phenols (22.30 +/- 0.23
      mg/g) and tannins (11.70 +/- 0.10 mg/g), C. aconitifolius of cyanogenic
      glycosides (5.02 +/- 0.37 ug/g) and P. hysterophorus of saponins (6.12 +/- 0.02
      mg/g). Tannins values obtained were not adverse to their consumption. Alcoholic
      and aqueous extracts of selected plants had hemolytic activity depending on the
      concentration of saponins. Although the values of cyanogenic glycosides were
      permissible, it was necessary to monitor the presence of this metabolite in
      plants to minimize health problems. LC50 values ranged from extremely toxic (3.37
      ug/mL) to highly toxic (274.34 MUg/mL), in P. carpunya and T. officinale,
      respectively. From correlation analysis, it was observed that increase values of
      alkaloids concentrations had highly significant (p<0.001) acute toxicity against
      A. salina, while at a higher polyphenol concentration the level of plants
      cytotoxicity decreased significantly (p<0.001). The results of principal
      component analysis showed that saponins apparently were in synergy with
      polyphenols to decrease cytotoxicity, but antagonize with alkaloids and
      cyanogenic glycosides, indicating that these secondary metabolites present
      variability in the mechanisms of action against A. salina, as cytotoxic
      compounds. These results also demonstrate that polyphenols and saponins can be
      lethal at low concentrations, demonstrating the potential of brine shrimp
      bioassay as a model to evaluate plant extracts containing low concentrations of
      chemical compounds with high polarities. The significant positive correlation
      between cytotoxicity and concentration of alkaloids confirmed by the bioassay of
      brine shrimp can be useful to identify promising sources of antitumor compounds,
      and to evaluate tolerable limits not affecting other benign cells. Contents of
      secondary metabolites found in the selected plants confer them great
      pharmacologic values.

PMID- 29461792
TI  - Enhanced Transparency of Rough Surface Sapphire by Surface Vitrifaction Process.
AB  - A novel, simple, and low-cost in situ surface vitrification method has been
      effectively developed to enhance the optical transparency of rough surface
      sapphire at UV-visible-IR regions. This method is to obtain a glass layer on the
      sapphire surface through vitrifaction process. The thickness, refractive index,
      components and transition temperature of the glass layer have been investigated
      and discussed respectively by XRD, DSC, SEM and EDS elemental analysis. The
      experimental results show that the vitrified sapphire has high transparency even
      after 1000  degrees C annealing at UV-visible-IR regions.

PMID- 29461793
TI  - Thermally Driven Self-Limiting Atomic Layer Etching of Metallic Tungsten Using
      WF6 and O2.
AB  - The semiconductor industry faces a tremendous challenge in the development of a
      transistor device with sub-10 nm complex features. Self-limiting atomic layer
      etching (ALE) is essential for enabling the manufacturing of complex transistor
      structures. In this study, we demonstrated a thermally driven ALE process for
      tungsten (W) using sequential exposures of O2 and WF6. Based on the insight
      gained from the previous study on TiO2 thermal ALE, we proposed that etching of W
      could proceed in two sequential reaction steps at 300  degrees C: (1) oxidation
      of metallic tungsten using O2 or O3 to form WO3(s) and (2) formation and removal
      of volatile WO2F2(g) during the reaction between WO3(s) and WF6(g). The O2/WF6
      etch process was experimentally studied using a quartz crystal microbalance
      (QCM). We find that both the O2 and WF6 ALE half reactions are self-limiting,
      with an estimated steady-state etch rate of ~6.3 A/cycle at 300  degrees C. We
      also find that etching of W proceeds readily at 300  degrees C, but not at
      temperatures lower than 275  degrees C. Thermodynamic modeling reveals that the
      observed temperature dependence is likely due to the limited volatility of WO2F2.
      The use of WF6 with O3 in place of O2 also allows W etching, where the stronger
      oxidant leads to a larger mass removal rate per cycle. However, we find O2 to be
      more controllable for precise metal removal per cycle. In addition, etched W
      films were examined with ex situ analytical tools. Using spectroscopic
      ellipsometry (SE) and scanning electron microscopy (SEM), we confirm etching of
      tungsten film on silicon substrates. Surface analysis by X-ray photoelectron
      spectroscopy (XPS) revealed a minimal fluorine content on the W film after
      partial etching and on the silicon surface after full etching. This suggests that
      W ALE does not significantly alter the chemical composition of W films. This work
      serves to increase the understanding of ALE reactions and expand the base of
      available ALE processes for advanced material processing.

PMID- 29461794
TI  - A New Generation of Surface Active Carbon Textiles As Reactive Adsorbents of
      Indoor Formaldehyde.
AB  - Highly porous carbon textiles were modified by impregnation with urea, thiourea,
      dicyandiamide, or penicillin G, followed by heat treatment at 800  degrees C.
      This resulted in an incorporation of nitrogen or nitrogen and sulfur heteroatoms
      in various configurations to the carbon surface. The volume of pores and,
      especially, ultramicropores was also affected to various extents. The modified
      textiles were then used as adsorbents of formaldehyde (1 ppmv) in dynamic
      conditions. The modifications applied significantly improved the adsorptive
      performance. For the majority of samples, formaldehyde adsorption resulted in a
      decrease in the volume of ultramicropores. The enhancement in the adsorption was
      linked not only to the physical adsorption of formaldehyde in small pores but
      also to its reactivity with sulfonic groups and amines present on the surface.
      Water on the surface and in challenge gas decreased the adsorptive performance
      owing to the competition with formaldehyde for polar centers. The results
      collected show that the S- and N-modified textiles can work as efficient media
      for indoor formaldehyde removal.

PMID- 29461795
TI  - Nanoengineered Ionic-Covalent Entanglement (NICE) Bioinks for 3D Bioprinting.
AB  - We introduce an enhanced nanoengineered ionic-covalent entanglement (NICE) bioink
      for the fabrication of mechanically stiff and elastomeric 3D biostructures. NICE
      bioink formulations combine nanocomposite and ionic-covalent entanglement (ICE)
      strengthening mechanisms to print customizable cell-laden constructs for tissue
      engineering with high structural fidelity and mechanical stiffness. Nanocomposite
      and ICE strengthening mechanisms complement each other through synergistic
      interactions, improving mechanical strength, elasticity, toughness, and flow
      properties beyond the sum of the effects of either reinforcement technique alone.
      Herschel-Bulkley flow behavior shields encapsulated cells from excessive shear
      stresses during extrusion. The encapsulated cells readily proliferate and
      maintain high cell viability over 120 days within the 3D-printed structure, which
      is vital for long-term tissue regeneration. A unique aspect of the NICE bioink is
      its ability to print much taller structures, with higher aspect ratios, than can
      be achieved with conventional bioinks without requiring secondary supports. We
      envision that NICE bioinks can be used to bioprint complex, large-scale, cell
      laden constructs for tissue engineering with high structural fidelity and
      mechanical stiffness for applications in custom bioprinted scaffolds and tissue
      engineered implants.

PMID- 29461796
TI  - More Than a Light Switch: Engineering Unconventional Fluorescent Configurations
      for Biological Sensing.
AB  - Fluorescence is a powerful and sensitive tool in biological detection, used
      widely for cellular imaging and in vitro molecular diagnostics. Over time, three
      prominent conventions have emerged in the design of fluorescent biosensors: a
      sensor is ideally specific for its target, only one fluorescence signal turns on
      or off in response to the target, and each target requires its own sensor and
      signal combination. These are conventions but not requirements, and sensors that
      break with one or more of these conventions can offer new capabilities and
      advantages. Here, we review "unconventional" fluorescent sensor configurations
      based on fluorescent dyes, proteins, and nanomaterials such as quantum dots and
      metal nanoclusters. These configurations include multifluorophore Forster
      resonance energy transfer (FRET) networks, temporal multiplexing, photonic logic,
      and cross-reactive arrays or "noses". The more complex but carefully engineered
      biorecognition and fluorescence signaling modalities in unconventional designs
      are richer in information, afford greater multiplexing capacity, and are
      potentially better suited to the analysis of complex biological samples,
      interactions, processes, and diseases. We conclude with a short perspective on
      the future of unconventional fluorescent sensors and encourage researchers to
      imagine sensing beyond the metaphorical light bulb and light switch combination.

PMID- 29461797
TI  - Identification of Protein Targets of 12/15-Lipoxygenase-Derived Lipid
      Electrophiles in Mouse Peritoneal Macrophages Using Omega-Alkynyl Fatty Acid.
AB  - The 12/15-lipoxygenase (12/15-LOX) enzyme introduces peroxyl groups, in a
      position-specific manner, into polyunsaturated fatty acids to form various kinds
      of bioactive lipid metabolites, including lipid-derived electrophiles (LDE). The
      resident peritoneal macrophage is the site of highest 12/15-LOX expression in the
      mouse. However, the role of the enzyme in the regulation of resident macrophages
      is not fully understood. Here, we describe a chemoproteomic method to identify
      the targets of enzymatically generated LDE. By treating mouse peritoneal
      macrophages with omega-alkynyl arachidonic acid (aAA), we identified a series of
      proteins adducted by LDE generated through a 12/15-LOX catalyzed reaction.
      Pathway analysis revealed a dramatic enrichment of proteins involved in energy
      metabolism and found that glycolytic flux and mitochondrial respiration were
      significantly affected by the expression of 12/15-LOX. Our findings thus
      highlight the utility of chemoproteomics using aAA for identifying intracellular
      targets of enzymatically generated LDE.

PMID- 29461798
TI  - Detection and Identification of Plant Pathogens on Maize Kernels with a Hand-Held
      Raman Spectrometer.
AB  - Rapid detection and identification of crop pathogens is essential for improving
      crop yield. Typical pathogen assaying methods, such as polymerase chain reaction
      (PCR) or enzyme-linked immunosorbent assay (ELISA), are time-consuming and
      destructive to the sample. Raman spectroscopy (RS) is a noninvasive
      nondestructive analytical technique that provides insight on the chemical
      structure of the specimen. In this study, we demonstrate that using a hand-held
      Raman spectrometer, in combination with chemometric analyses, we can distinguish
      between healthy and diseased maize ( Zea mays) kernels, as well as between
      different diseases with 100% accuracy. Our analysis is portable and sample
      agnostic, suggesting that it could be retooled for other crops and conducted
      autonomously.

PMID- 29461799
TI  - Laser Ablation-Aerosol Mass Spectrometry-Chemical Ionization Mass Spectrometry
      for Ambient Surface Imaging.
AB  - Mass spectrometry imaging is becoming an increasingly common analytical technique
      due to its ability to provide spatially resolved chemical information. Here, we
      report a novel imaging approach combining laser ablation with two mass
      spectrometric techniques, aerosol mass spectrometry and chemical ionization mass
      spectrometry, separately and in parallel. Both mass spectrometric methods provide
      the fast response, rapid data acquisition, low detection limits, and high
      resolution peak separation desirable for imaging complex samples. Additionally,
      the two techniques provide complementary information with aerosol mass
      spectrometry providing near universal detection of all aerosol molecules and
      chemical ionization mass spectrometry with a heated inlet providing molecular
      level detail of both gases and aerosols. The two techniques operate with
      atmospheric pressure interfaces and require no matrix addition for ionization,
      allowing for samples to be investigated in their native state under ambient
      pressure conditions. We demonstrate the ability of laser ablation-aerosol mass
      spectrometry-chemical ionization mass spectrometry (LA-AMS-CIMS) to create 2D
      images of both standard compounds and complex mixtures. The results suggest that
      LA-AMS-CIMS, particularly when combined with advanced data analysis methods,
      could have broad applications in mass spectrometry imaging applications.

PMID- 29461800
TI  - Antisense Inhibitors Retain Activity in Pulmonary Models of Burkholderia
      Infection.
AB  - The Burkholderia cepacia complex is a group of Gram-negative bacteria that are
      opportunistic pathogens in immunocompromised individuals, such as those with
      cystic fibrosis (CF) or chronic granulomatous disease (CGD). Burkholderia are
      intrinsically resistant to many antibiotics and the lack of antibiotic
      development necessitates novel therapeutics. Peptide-conjugated
      phosphorodiamidate morpholino oligomers are antisense molecules that inhibit
      bacterial mRNA translation. Targeting of PPMOs to the gene acpP, which is
      essential for membrane synthesis, lead to defects in the membrane and ultimately
      bactericidal activity. Exploration of additional PPMO sequences identified the
      ATG and Shine-Dalgarno sites as the most efficacious for targeting acpP. The CF
      lung is a complex microenvironment, but PPMO inhibition was still efficacious in
      an artificial model of CF sputum. PPMOs had low toxicity in human CF cells at
      doses that were antibacterial. PPMOs also reduced the bacterial burden in the
      lungs of immunocompromised CyBB mice, a model of CGD. Finally, the use of
      multiple PPMOs was efficacious in inhibiting the growth of both Burkholderia and
      Pseudomonas in an in vitro model of coinfection. Due to the intrinsic resistance
      of Burkholderia to traditional antibiotics, PPMOs represent a novel and viable
      approach to the treatment of Burkholderia infections.

PMID- 29461801
TI  - Development and Characterization of a Laser-Induced Acoustic Desorption Source.
AB  - A laser-induced acoustic desorption source, developed for use at central
      facilities, such as free-electron lasers, is presented. It features prolonged
      measurement times and a fixed interaction point. A novel sample deposition method
      using aerosol spraying provides a uniform sample coverage and hence stable signal
      intensity. Utilizing strong-field ionization as a universal detection scheme, the
      produced molecular plume is characterized in terms of number density, spatial
      extend, fragmentation, temporal distribution, translational velocity, and
      translational temperature. The effect of desorption laser intensity on these
      plume properties is evaluated. While translational velocity is invariant for
      different desorption laser intensities, pointing to a nonthermal desorption
      mechanism, the translational temperature increases significantly and higher
      fragmentation is observed with increased desorption laser fluence.

PMID- 29461802
TI  - Ionization of Gas-Phase Polycyclic Aromatic Hydrocarbons in Electrospray
      Ionization Coupled with Gas Chromatography.
AB  - Herein, gas-phase polycyclic aromatic hydrocarbons (PAHs) as nonpolar compounds
      were ionized to protonated molecular ions [M + H]+ without radical cations and
      simultaneously analyzed using gas chromatography (GC)/electrospray ionization
      (ESI)-tandem mass spectrometry (MS/MS). The ionization profile, dissociation, and
      sensitivity were first investigated to understand the significant behavior of gas
      phase PAHs under ESI. The formation of protonated molecular ions of PAHs was
      distinguished according to the analyte phase and ESI spray solvents. The
      protonated PAHs exhibited characteristic dissociations, such as H-loss, H2-loss,
      and acetylene-loss, via competition of internal energy. In addition, GC/ESI-MS/MS
      resulted in relatively lower concentration levels (better sensitivity) for the
      limits-of-detection (LODs) of PAHs than liquid chromatography (LC)/ESI-MS/MS, and
      it seems to result from the characteristic ionization mechanism of the gas-phase
      analyte under ESI. Furthermore, the LODs of gas-phase PAHs depended on molecular
      weight and proton affinity (PA). Consequently, we demonstrated the relationship
      among the analyte phases, sensitivities, and structural characteristics
      (molecular weight and PA) under ESI. The gas-phase PAHs provided enhanced
      protonation efficiency and sensitivity using GC/ESI-MS/MS, as their molecular
      weight and PA increased. Based on these results, we offered important information
      regarding the behavior of gas-phase analytes under ESI. Therefore, the present
      GC/ESI-MS/MS method has potential as an alternative method for simultaneous
      analysis of PAHs.

PMID- 29461803
TI  - Exploring Ion Suppression in Mass Spectrometry Imaging of a Heterogeneous Tissue.
AB  - In this study we have explored several aspects of regional analyte suppression in
      mass spectrometry imaging (MSI) of a heterogeneous sample, transverse
      cryosections of mouse brain. Olanzapine was homogeneously coated across the
      section prior to desorption electrospray ionization (DESI) and matrix-assisted
      laser desorption ionization (MALDI) mass spectrometry imaging. We employed the
      concept of a tissue extinction coefficient (TEC) to assess suppression of an
      analyte on tissue relative to its intensity in an off tissue region. We expanded
      the use of TEC, by first segmenting anatomical regions using graph-cuts
      clustering and calculating a TEC for each cluster. The single ion image of the
      olanzapine [M + H]+ ion was seen to vary considerably across the image, with
      anatomical features such as the white matter and hippocampus visible. While
      trends in regional ion suppression were conserved across MSI modalities,
      significant changes in the magnitude of relative regional suppression effects
      between techniques were seen. Notably the intensity of olanzapine was less
      suppressed in DESI than for MALDI. In MALDI MSI, significant differences in the
      concentration dependence of regional TECs were seen, with the TEC of white matter
      clusters exhibiting a notably stronger correlation with concentration than for
      clusters associated with gray matter regions. We further employed cluster
      specific TECs as regional normalization factors. In comparison to published pixel
      by-pixel normalization methods, regional TEC normalization exhibited superior
      reduction ion suppression artifacts. We also considered the usefulness of a
      segmentation-based approach to compare spectral information obtained from
      complementary modalities.

PMID- 29461804
TI  - A Switchable Site-Specific Antibody Conjugate.
AB  - Genetic incorporation of unnatural amino acids (UAAs) provides a unique approach
      to the synthesis of site-specific antibody conjugates that are homogeneous and
      better defined constructs than random conjugates. Yet, the yield varies for every
      antibody, and the process is costly and time-consuming. We have developed a
      switchable alphaGCN4-Fab conjugate that incorporates UAA p-acetylphenylalanine.
      The GCN4 peptide is used as a switch, and antibodies fused by GCN4 can direct the
      alphaGCN4-Fab conjugate to target different cancer cells for diagnosis, imaging,
      or therapeutic treatment. More importantly, this switchable conjugate
      demonstrated an impressive potential for pretargeted imaging in vivo. This
      approach illustrates the utility of an orthogonal switch as a general strategy to
      endow versatility to a single antibody conjugate, which should facilitate the
      application of UAA-based site-specific conjugates for a host of biomedical uses
      in the future.

PMID- 29461805
TI  - Autofluorescence-Free Live-Cell Imaging Using Terbium Nanoparticles.
AB  - Fluorescent nanoparticles (NPs) have become irreplaceable tools for advanced
      cellular and subcellular imaging. While very bright NPs require excitation with
      UV or visible light, which can create strong autofluorescence of biological
      components, NIR-excitable NPs without autofluorescence issues exhibit much lower
      brightness. Here, we show the application of a new type of surface
      photosensitized terbium NPs (Tb-NPs) for autofluorescence-free intracellular
      imaging in live HeLa cells. The combination of exceptionally high brightness,
      high photostability, and long photoluminecence (PL) lifetimes for highly
      efficient suppression of the short-lived autofluorescence allowed for time-gated
      PL imaging of intracellular vesicles over 72 h without toxicity and at extremely
      low Tb-NP concentrations down to 12 pM. Detection of highly resolved long
      lifetime (ms) PL decay curves from small (~10 MUm2) areas within single cells
      within a few seconds emphasized the unprecedented photophysical properties of Tb
      NPs for live-cell imaging that extend well beyond currently available nanometric
      imaging agents.

PMID- 29461806
TI  - White-Light Emission from Layered Halide Perovskites.
AB  - With nearly 20% of global electricity consumed by lighting, more efficient
      illumination sources can enable massive energy savings. However, effectively
      creating the high-quality white light required for indoor illumination remains a
      challenge. To accurately represent color, the illumination source must provide
      photons with all the energies visible to our eye. Such a broad emission is
      difficult to achieve from a single material. In commercial white-light sources,
      one or more light-emitting diodes, coated by one or more phosphors, yield a
      combined emission that appears white. However, combining emitters leads to
      changes in the emission color over time due to the unequal degradation rates of
      the emitters and efficiency losses due to overlapping absorption and emission
      energies of the different components. A single material that emits broadband
      white light (a continuous emission spanning 400-700 nm) would obviate these
      problems. In 2014, we described broadband white-light emission upon near-UV
      excitation from three new layered perovskites. To date, nine white-light-emitting
      perovskites have been reported by us and others, making this a burgeoning field
      of study. This Account outlines our work on understanding how a bulk material,
      with no obvious emissive sites, can emit every color of the visible spectrum.
      Although the initial discoveries were fortuitous, our understanding of the
      emission mechanism and identification of structural parameters that correlate
      with the broad emission have now positioned us to design white-light emitters.
      Layered hybrid halide perovskites feature anionic layers of corner-sharing metal
      halide octahedra partitioned by organic cations. The narrow, room-temperature
      photoluminescence of lead-halide perovskites has been studied for several
      decades, and attributed to the radiative recombination of free excitons (excited
      electron-hole pairs). We proposed that the broad white emission we observed
      primarily stems from exciton self-trapping. Here, the exciton couples strongly to
      the lattice, creating transient elastic lattice distortions that can be viewed as
      "excited-state defects". These deformations stabilize the exciton affording a
      broad emission with a large Stokes shift. Although material defects very likely
      contribute to the emission width, our mechanistic studies suggest that the
      emission mostly arises from the bulk material. Ultrafast spectroscopic
      measurements support self-trapping, with new, transient, electronic states
      appearing upon photoexcitation. Importantly, the broad emission appears common to
      layered Pb-Br and Pb-Cl perovskites, albeit with a strong temperature dependence.
      Although the emission is attributed to light-induced defects, it still reflects
      changes in the crystal structure. We find that greater out-of-plane octahedral
      tilting increases the propensity for the broad emission, enabling synthetic
      control over the broad emission. Many of these perovskites have color rendering
      abilities that exceed commercial requirements and mixing halides affords both
      "warm" and "cold" white light. The most efficient white-light-emitting perovskite
      has a quantum efficiency of 9%. Improving this value will make these phosphors
      attractive for solid-state lighting, particularly as large-area coatings that can
      be deposited inexpensively. The emission mechanism can also be extended to other
      low-dimensional systems. We hope this Account aids in expanding the phase space
      of white-light emitters and controlling their exciton dynamics by the synthetic,
      spectroscopic, theoretical, and engineering communities.

PMID- 29461807
TI  - Soft Argon-Propane Dielectric Barrier Discharge Ionization.
AB  - Dielectric barrier discharges (DBDs) have been used as soft ionization sources
      (DBDI) for organic mass spectrometry (DBDI-MS) for approximately ten years.
      Helium-based DBDI is often used because of its good ionization efficiency, low
      ignition voltage, and homogeneous plasma conditions. Argon needs much higher
      ignition voltages than helium when the same discharge geometry is used. A
      filamentary plasma, which is not suitable for soft ionization, may be produced
      instead of a homogeneous plasma. This difference results in N2, present in helium
      and argon as an impurity, being Penning-ionized by helium but not by metastable
      argon atoms. In this study, a mixture of argon and propane (C3H8) was used as an
      ignition aid to decrease the ignition and working voltages, because propane can
      be Penning-ionized by argon metastables. This approach leads to homogeneous argon
      based DBDI. Furthermore, operating DBDI in an open environment assumes that many
      uncharged analyte molecules do not interact with the reactant ions. To overcome
      this disadvantage, we present a novel approach, where the analyte is introduced
      in an enclosed system through the discharge capillary itself. This nonambient
      DBDI-MS arrangement is presented and characterized and could advance the novel
      connection of DBDI with analytical separation techniques such as gas
      chromatography (GC) and high-pressure liquid chromatography (HPLC) in the near
      future.

PMID- 29461808
TI  - TiO2-Assisted Laser Desorption/Ionization Mass Spectrometry for Rapid Profiling
      of Candidate Metabolite Biomarkers from Antimicrobial-Resistant Bacteria.
AB  - Antimicrobial resistance (AMR) is one of the most serious problems affecting
      public health and safety. It is crucial to understand antimicrobial resistance
      from the molecular level. In this work, TiO2-assisted laser desorption/ionization
      (LDI) mass spectrometry (MS) was used for the fast metabolites analysis from
      intact bacterial cells to discriminate different strains of bacteria and to
      detect AMR. With the mass spectra of bacterial metabolites by TiO2-LDI MS,
      multivariable analysis was performed for bacterial identification to determine
      distinctive metabolites as the potential biomarkers. The most statistically
      significant metabolites were screened out by the method and further identified
      using liquid-chromatography (LC) tandem MS (MS/MS). Robustness of our developed
      methods in bacterial taxonomy was demonstrated by iterative validation using 48
      clinical samples. The strategy was further illustrated with three clinical
      strains of ESBL (extended-spectrum beta-lactamase-resistant)-positive
      Escherichia. coli and four clinical strains of ESBL-negative ones. Eleven key
      metabolites were identified as potential biomarkers of ESBL-positive E. coli. We
      also implemented the pathway and network analysis on the key metabolites to prove
      the feasibility of our method in executing metabolomics analysis. Compared to the
      most prevalent techniques in a metabolomics study, such as LC-MS, gas
      chromatography MS, and nuclear magnetic resonance spectroscopy, the current
      method has advantages in its simple sample preparation and short analysis time,
      thereby fitting especially into clinical usages and fast analyses.

PMID- 29461809
TI  - Protein-Mediated Shape Control of Silver Nanoparticles.
AB  - Silver nanoparticles were grown in aqueous solution, without the presence of
      typical surfactant molecules, but under the presence of different proteins. The
      shape of the resulting silver nanoparticles could be tuned by the selection of
      the types of proteins. The amount of accessible lysine groups was found to be
      mainly responsible for the anisotropy in nanoparticle formation. Viability
      measurements of cells exposed to protein capped spherical or prism-shaped NPs did
      not reveal differences between both geometries. Thus, in the case of protein-only
      coated Ag NPs, no shape-induced toxicity was found under the investigated
      exposure conditions.

PMID- 29461810
TI  - Microbial Community Composition of Tap Water and Biofilms Treated with or without
      Copper-Silver Ionization.
AB  - Copper-silver ionization (CSI) is an in-house water disinfection method primarily
      installed to eradicate Legionella bacteria from drinking water distribution
      systems (DWDS). Its effect on the abundance of culturable Legionella and
      Legionella infections has been documented in several studies. However, the effect
      of CSI on other bacteria in DWDS is largely unknown. To investigate these
      effects, we characterized drinking water and biofilm communities in a hospital
      using CSI, in a neighboring building without CSI, and in treated drinking water
      at the local water treatment plant. We used 16S rDNA amplicon sequencing and
      Legionella culturing. The sequencing results revealed three distinct water
      groups: (1) cold-water samples (no CSI), (2) warm-water samples at the research
      institute (no CSI), and (3) warm-water samples at the hospital (after CSI;
      ANOSIM, p < 0.001). Differences between the biofilm communities exposed and not
      exposed to CSI were less clear (ANOSIM, p = 0.022). No Legionella were cultured,
      but limited numbers of Legionella sequences were recovered from all 25 water
      samples (0.2-1.4% relative abundance). The clustering pattern indicated local
      selection of Legionella types (Kruskal-Wallis, p < 0.001). Furthermore, one
      unclassified Betaproteobacteria OTU was highly enriched in CSI-treated warm water
      samples at the hospital (Kruskal-Wallis, p < 0.001).

PMID- 29461811
TI  - eta2-SO2 Linkage Photoisomer of an Osmium Coordination Complex.
AB  - We report the discovery of an eta2-SO2 linkage photoisomer in the osmium
      pentaammine coordination complex, [Os(NH3)5(SO2)][Os(NH3)5(HSO3)]Cl4 (1). Its
      dark- and light-induced crystal structures are determined via synchrotron X-ray
      crystallography, at 100 K, where the photoinduced state is metastable in a single
      crystal that has been stimulated by 505 nm light for 2.5 h. The SO2 photoisomer
      in the [Os(NH3)5(SO2)]2+ cation contrasts starkly with the photoinactivity of the
      HSO3 ligand in its companion [Os(NH3)5(HSO3)]+ cation within the crystallographic
      asymmetric unit of this single crystal. Panchromatic optical absorption
      characteristics of this single crystal are revealed in both dark- and light
      induced states, using concerted absorption spectroscopy and optical microscopy.
      Its absorption halves across most of its visible spectrum, upon exposure to 505
      nm light. The SO2 ligand seems to be responsible for this photoinduced bleaching
      effect, judging from a comparison of the dark- and light-induced crystal
      structures of 1. The SO2 photoisomerism is found to be thermally reversible, and
      so 1 presents a rare example of an osmium-based solid-state optical switch. Such
      switching in an osmium complex is significant because bottom-row transition
      metals stand to offer linkage photoisomerism with the greatest photoconversion
      levels and thermal stability. The demonstration of eta2-SO2 bonding in this
      complex also represents a fundamental contribution to osmium coordination
      chemistry.

PMID- 29461812
TI  - Molecularly Imprinted Polymer as an Antibody Substitution in Pseudo-immunoassays
      for Chemical Contaminants in Food and Environmental Samples.
AB  - The chemical contaminants in food and the environment are quite harmful to food
      safety and human health. Rapid, accurate, and cheap detection can effectively
      control the potential risks derived from these chemical contaminants. Among all
      detection methods, the immunoassay based on the specific interaction of antibody
      analyte is one of the most widely used techniques in the field. However,
      biological antibodies employed in the immunoassay usually cannot tolerate extreme
      conditions, resulting in an unstable state in both physical and chemical
      profiles. Molecularly imprinted polymers (MIPs) are a class of polymers with
      specific molecular recognition abilities, which are highly robust, showing
      excellent operational stability under a wide variety of conditions. Recently,
      MIPs have been used in biomimetic immunoassays for chemical contaminants as an
      antibody substitute in food and the environment. Here, we reviewed these
      applications of MIPs incorporated in different analytical platforms, such as
      enzyme-linked immunosorbent assay, fluorescent immunoassay, chemiluminescent
      immunoassay, electrochemical immunoassay, microfluidic paper-based immunoassay,
      and homogeneous immunoassay, and discussed current challenges and future trends
      in the use of MIPs in biomimetic immunoassays.

PMID- 29461813
TI  - Ligand-Controlled Chemoselective C(acyl)-O Bond vs C(aryl)-C Bond Activation of
      Aromatic Esters in Nickel Catalyzed C(sp2)-C(sp3) Cross-Couplings.
AB  - A ligand-controlled and site-selective nickel catalyzed Suzuki-Miyaura cross
      coupling reaction with aromatic esters and alkyl organoboron reagents as coupling
      partners was developed. This methodology provides a facile route for C(sp2)
      C(sp3) bond formation in a straightforward fashion by successful suppression of
      the undesired beta-hydride elimination process. By simply switching the
      phosphorus ligand, the ester substrates are converted into the alkylated arenes
      and ketone products, respectively. The utility of this newly developed protocol
      was demonstrated by its wide substrate scope, broad functional group tolerance
      and application in the synthesis of key intermediates for the synthesis of
      bioactive compounds. DFT studies on the oxidative addition step helped
      rationalizing this intriguing reaction chemoselectivity: whereas nickel complexes
      with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative
      addition step leading to the alkylated product via a decarbonylative process,
      nickel complexes with monodentate phosphorus ligands favor activation of the
      C(acyl)-O bond, which later generates the ketone product.

PMID- 29461814
TI  - Machine Learning of Partial Charges Derived from High-Quality Quantum-Mechanical
      Calculations.
AB  - Parametrization of small organic molecules for classical molecular dynamics
      simulations is not trivial. The vastness of the chemical space makes approaches
      using building blocks challenging. The most common approach is therefore an
      individual parametrization of each compound by deriving partial charges from
      semiempirical or ab initio calculations and inheriting the bonded and van der
      Waals (Lennard-Jones) parameters from a (bio)molecular force field. The quality
      of the partial charges generated in this fashion depends on the level of the
      quantum-chemical calculation as well as on the extraction procedure used. Here,
      we present a machine learning (ML) based approach for predicting partial charges
      extracted from density functional theory (DFT) electron densities. The training
      set was chosen with the goal to provide a broad coverage of the known chemical
      space of druglike molecules. In addition to the speed of the approach, the
      partial charges predicted by ML are not dependent on the three-dimensional
      conformation in contrast to the ones obtained by fitting to the electrostatic
      potential (ESP). To assess the quality and compatibility with standard force
      fields, we performed benchmark calculations for the free energy of hydration and
      liquid properties such as density and heat of vaporization.

PMID- 29461815
TI  - Mechanistic Insights into the Activation of Soluble Guanylate Cyclase by Carbon
      Monoxide: A Multistep Mechanism Proposed for the BAY 41-2272 Induced Formation of
      5-Coordinate CO-Heme.
AB  - Soluble guanylate cyclase (sGC) is a heme-containing enzyme that catalyzes cGMP
      production upon sensing NO. While the CO adduct, sGC-CO, is much less active, the
      allosteric regulator BAY 41-2272 stimulates the cGMP productivity to the same
      extent as that of sGC-NO. The stimulatory effect has been thought to be likely
      associated with Fe-His bond cleavage leading to 5-coordinate CO-heme, but the
      detailed mechanism remains unresolved. In this study, we examined the mechanism
      under the condition including BAY 41-2272, 2'-deoxy-3'-GMP and foscarnet. The
      addition of these effectors caused the original 6-coordinate CO-heme to convert
      to an end product that was an equimolar mixture of a 5- and a new 6-coordinate CO
      heme, as assessed by IR spectral measurements. The two types of CO-hemes in the
      end product were further confirmed by CO dissociation kinetics. Stopped-flow
      measurements under the condition indicated that the ferrous sGC bound CO as two
      reversible steps, where the primary step was assigned to the full conversion of
      the ferrous enzyme to the 6-coordinate CO-heme, and subsequently followed by the
      slower second step leading a partial conversion of the 6-coordinate CO-heme to
      the 5-coordinate CO-heme. The observed rates for both steps linearly depended on
      CO concentrations. The unexpected CO dependence of the rates in the second step
      supports a multistep mechanism, in which the 5-coordinate CO-heme is led by CO
      release from a putative bis-carbonyl intermediate that is likely provided by the
      binding of a second CO to the 6-coordinate CO-heme. This mechanism provides a new
      aspect on the activation of sGC by CO.

PMID- 29461816
TI  - Photolytic Reactivity of Organometallic Chromium Bipyridine Complexes.
AB  - Known stable [Cr(bpy)2(Ph)2](BPh4) complexes undergo reductive elimination of
      biphenyl with visible-light photolysis using household incandescent or compact
      fluorescent light bulbs. A series of [Cr(R-bpy)2(Ar)2](X) complexes (R = H or
      CMe3; Ar = Ph, C6H4-CMe3, or C6H4-OMe; X = I, BPh4, or PF6) were prepared, and
      the effect of varying the bipyridine and aryl ligands on the UV-visible spectra
      and electrochemistry of the chromium(III) complexes was investigated. Photolysis
      of a mixture of two different bis(aryl) complexes gave only the homocoupled
      biaryl products by 1H NMR and gas chromatography/mass spectrometry analysis. The
      initial product of photoinduced reductive elimination of [Cr(bpy)2(Ar)2](PF6) was
      trapped with bipyridine to generate [Cr(bpy)3](PF6) and with benzoyl peroxide to
      form [Cr(bpy)2(O2CPh)2](PF6). The latter chromium(III) bis(benzoate) complex was
      also synthesized by the addition of bipyridine and PhCO2H to Cp2Cr, followed by
      air oxidation. The neutral Cr(bpy)(S2CNMe2)Ph2 complex also generated biphenyl
      upon visible-light photolysis. While the treatment of Cr(tBu-bpy)(dpm)Cl2 [dpm =
      (OCtBu)2CH] with AgO2CPh gave trans-Cr(tBu-bpy)(dpm)(O2CPh)2, reaction of the
      dichloro precursor with PhMgCl produced anionic [Cr(tBu-bpy)Ph3]- with
      [Mg(dpm)(THF)4]+ as the countercation, with both complexes characterized by
      single-crystal X-ray diffraction. Protonolysis of Cr(bpy)Ph3(THF) with 8
      hydroxyquinoline produced Cr(bpy)(quin)Ph2, which generated biphenyl under
      visible-light photolysis, and the initial product of reductive elimination was
      trapped by bipyridine or benzoyl peroxide. A related Cr(bpy)(quin)2 complex was
      synthesized by protonolysis of Cr(bpy)[N(SiMe3)2]2 and characterized by single
      crystal X-ray diffraction.

PMID- 29461817
TI  - Pentagonal-Bipyramid Ln(III) Complexes Exhibiting Single-Ion-Magnet Behavior: A
      Rational Synthetic Approach for a Rigid Equatorial Plane.
AB  - A pentadentate chelating ligand is employed for the facile synthesis of air
      stable pentagonal-bipyramid Ln(III) complexes with a rigid equatorial plane. The
      Dy(III) analogue exhibits single-ion-magnet behavior with Ueff/ kB = 70 K under
      Hdc = 500 Oe.

PMID- 29461818
TI  - Intermolecular Interaction Tuning of Spin-Crossover Iron(III) Complexes with
      Aromatic Counteranions.
AB  - Iron(III) spin-crossover (SCO) complexes [Fe(qsal)2]BS.MeOH.H2O (1),
      [Fe(qsal)2](NS).MeOH (2), [Fe(qnal)2](NS) (3), and [Fe(qnal)2]PS.MeOH.CH2Cl2 (4)
      (Hqsal, N-(8-quinolinyl)salicylaldimine; Hqnal, N-(8-quinolinyl)-2-hydroxy-1
      naphthaldimine; BS, benzenesulfonate; NS, 1-naphthalenesulfonate; PS, 1
      pyrenesulfonate) have been synthesized and characterized by X-ray structure
      determinations and temperature-dependent magnetic susceptibility measurements.
      The aromatic counteranions BS, NS, and PS can be used for the tuning of
      intermolecular coupling through a variety of weak interactions. All of the
      complexes show temperature-dependent SCO behavior. but the light-induced excited
      spin-state trapping (LIESST) effect was observed only for 1, 3, and 4 when the
      samples were illuminated (lambda 808 nm) for 1 h at 5 K. In particular, 59% of
      the LS form of 1 was converted to the metastable HS state by illumination, equal
      to the highest degree of conversion yet known for LIESST in [Fe(qsal)2]+
      derivatives. The lack of a LIESST effect for 2 may be due to the relatively
      limited degree of interaction between the cations and anions in the lattice,
      reflected in a much longer minimum Fe...Fe separation in this complex in
      comparison to the others.

PMID- 29461819
TI  - Enhanced Arylamine N-Oxygenase Activity of Polymer-Enzyme Assemblies by
      Facilitating Electron-Transferring Efficiency.
AB  - A novel N-oxygenase-coated core-shell nanoparticle was generated through the
      coassembly of poly(4-vinylpyridine) (P4VP) and arylamine N-oxygenase CmlI. The
      resulting enzyme-hybridized particles, P4VP-CmlI, showed excellent catalytic
      activities on the oxidation of two arylamine substrates, i.e., p-aminophenol (
      pAP) and p-aminobenzoic acid ( pABA), using a surrogate redox system or a
      peroxide shunt as co-oxidants. In comparison with the free enzyme, P4VP-CmlI
      particles exhibited a significantly enhanced catalytic efficiency when using
      pyridine nucleotide (NADH) and proper redox mediators. Products at different
      oxygenation stages were observed. On the contrary, the activity of the enzyme
      containing nanoparticles was very similar to the free enzyme when using the
      peroxide shunt. The enhanced catalytic efficiency of the P4VP-CmlI assemblies is
      attributed to a more efficient electron delivery.

PMID- 29461820
TI  - Evolution of the Complex Refractive Index of Secondary Organic Aerosols during
      Atmospheric Aging.
AB  - The wavelength-dependence of the complex refractive indices (RI) in the visible
      spectral range of secondary organic aerosols (SOA) are rarely studied, and the
      evolution of the RI with atmospheric aging is largely unknown. In this study, we
      applied a novel white light-broadband cavity enhanced spectroscopy to measure the
      changes in the RI (400-650 nm) of beta-pinene and p-xylene SOA produced and aged
      in an oxidation flow reactor, simulating daytime aging under NO x-free
      conditions. It was found that these SOA are not absorbing in the visible range,
      and that the real part of the RI, n, shows a slight spectral dependence in the
      visible range. With increased OH exposure, n first increased and then decreased,
      possibly due to an increase in aerosol density and chemical mean polarizability
      for SOA produced at low OH exposures, and a decrease in chemical mean
      polarizability for SOA produced at high OH exposures, respectively. A simple
      radiative forcing calculation suggests that atmospheric aging can introduce more
      than 40% uncertainty due to the changes in the RI for aged SOA.

PMID- 29461821
TI  - Analyte-Driven Disassembly and Turn-On Fluorescent Sensing in Competitive
      Biological Media.
AB  - Many indicator displacement assays can detect biological analytes in water, but
      these often have reduced performance in the presence of an unavoidable component:
      NaCl. We report here a new self-assembled sensor, DimerDye, that uses a novel
      photochemical guest-sensing mechanism and that is intrinsically tolerant of
      cosolutes. We synthetically integrated a dye into a calixarene macrocycle,
      forming two new merocyanine calixarenes (MCx-1 and MCx-2). Both compounds self
      assemble into nonemissive dimers in water. The addition of good guests like
      trimethyllysine induces a turn-on fluorescence response of MCx-1 due to
      simultaneous dimer dissociation and formation of an emissive host-guest complex.
      DimerDyes remain functional in solutions containing the various salts, metal
      ions, and cofactors that are needed for enzymatic reactions. MCx-1 provides a
      real-time, turn-on fluorescence signal in response to the lysine
      methyltransferase reaction of PRDM9.

PMID- 29461822
TI  - Application and Limitations of Nanocasting in Metal-Organic Frameworks.
AB  - Nanocasting can be a useful strategy to transfer the catalytic metal clusters in
      metal-organic frameworks (MOFs) to an all-inorganic support such as silica. The
      incorporation of silica in the MOF pores as a secondary support has the potential
      to extend the application of the highly tunable metal-based active sites in MOFs
      to high temperature catalysis. Here, we demonstrate the applicability of the
      nanocasting method to a range of MOFs that incorporate catalytically attractive
      hexazirconium, hexacerium, or pentanickel oxide-based clusters (UiO-66, (Ce)UiO
      66, (Ce)UiO-67, (Ce)MOF-808, DUT-9, and In- and Ni-postmetalated NU-1000). We
      describe, in tutorial form, the challenges associated with nanocasting of MOFs
      that are related to their small pore size and to considerations of chemical and
      mechanical stability, and we provide approaches to overcome some of these
      challenges. Some of these nanocast materials feature the site-isolated clusters
      in a porous, thermally stable silica matrix, suitable for catalysis at high
      temperatures; in others, structural rearrangement of clusters or partial cluster
      aggregation occurs, but extensive aggregation can be mitigated by the silica
      skeleton introduced during nanocasting.

PMID- 29461824
TI  - Resolving the (19 R) Absolute Configuration of Lanciferine, a Monoterpene Indole
      Alkaloid from Alstonia boulindaensis.
AB  - Reinvestigation of the structure of lanciferine (1a) through extensive
      spectroscopic analysis in conjunction with a detailed computational study led to
      the unambiguous assignment of its (19 R) absolute configuration, thus leading to
      the full (2 R, 3 S, 7 S, 15 R, 16 R, 19 R, 20 S) assignment of lanciferine 45
      years after its isolation.

PMID- 29461823
TI  - Development of (6 R)-2-Nitro-6-[4-(trifluoromethoxy)phenoxy]-6,7-dihydro-5 H
      imidazo[2,1- b][1,3]oxazine (DNDI-8219): A New Lead for Visceral Leishmaniasis.
AB  - Discovery of the potent antileishmanial effects of antitubercular 6-nitro-2,3
      dihydroimidazo[2,1- b][1,3]oxazoles and 7-substituted 2-nitro-5,6
      dihydroimidazo[2,1- b][1,3]oxazines stimulated the examination of further
      scaffolds (e.g., 2-nitro-5,6,7,8-tetrahydroimidazo[2,1- b][1,3]oxazepines), but
      the results for these seemed less attractive. Following the screening of a 900
      compound pretomanid analogue library, several hits with more suitable potency,
      solubility, and microsomal stability were identified, and the superior efficacy
      of newly synthesized 6 R enantiomers with phenylpyridine-based side chains was
      established through head-to-head assessments in a Leishmania donovani mouse
      model. Two such leads ( R-84 and R-89) displayed promising activity in the more
      stringent Leishmania infantum hamster model but were unexpectedly found to be
      potent inhibitors of hERG. An extensive structure-activity relationship
      investigation pinpointed two compounds ( R-6 and pyridine R-136) with better
      solubility and pharmacokinetic properties that also provided excellent oral
      efficacy in the same hamster model (>97% parasite clearance at 25 mg/kg, twice
      daily) and exhibited minimal hERG inhibition. Additional profiling earmarked R-6
      as the favored backup development candidate.

PMID- 29461825
TI  - Palladium-Catalyzed Sequential Heteroarylation/Acylation Reactions of
      Iodobenzenes: Synthesis of Functionalized Benzo[ d]oxazoles.
AB  - We report an efficient palladium-catalyzed approach to the synthesis of
      benzoxazole derivatives via sequential heteroarylation/acylation reaction of
      iodobenzenes. Three readily available starting materials, iodobenzenes,
      anhydrides, and benzoxazoles, were smoothly coupled to form new C-C bonds at the
      ortho and ipso positions of the iodobenzenes to afford 2-heteroaryl-3-acylbenzene
      derivatives in good yields.

PMID- 29461826
TI  - Information Entropy of Liquid Metals.
AB  - Correlations reduce the configurational entropies of liquids below their ideal
      gas limits. By means of first-principles molecular dynamics simulations, we
      obtain accurate pair correlation functions of liquid metals, then subtract the
      mutual information content of these correlations from the ideal gas entropies to
      predict the absolute entropies over a broad range of temperatures. We apply this
      method to liquid aluminum and copper and demonstrate good agreement with
      experimental measurements; then, we apply it to predict the entropy of a liquid
      aluminum-copper alloy. Corrections due to electronic entropy and many-body
      correlations are discussed.

PMID- 29461827
TI  - Current Insights of BRAF Inhibitors in Cancer.
AB  - Oncogenic BRAF kinase deregulates the ERK signaling pathway in a large number of
      human tumors. FDA-approved BRAF inhibitors for BRAFV600E/K tumors have provided
      impressive clinical responses extending survival of melanoma patients. However,
      these drugs display paradoxical activation in normal tissue with BRAFWT due to
      RAF transactivation and priming, acquired drug resistance, and limited clinical
      effectiveness in non-V600 BRAF-dependent tumors, underscoring the urgent need to
      develop improved BRAF inhibitors. This review provides an overview of recent
      structural and biochemical insights into the mechanisms of BRAF regulation by
      BRAF inhibitors that are linked to their clinical activity, clinical liabilities,
      and medicinal chemistry properties. The effectiveness and challenges of
      structurally diverse next generation RAF inhibitors currently in preclinical and
      clinical development are discussed, along with mechanistic insights for
      developing more effective RAF inhibitors targeting different oncogenic BRAF
      conformations.

PMID- 29461828
TI  - Spin-Orbit Coupling via Four-Component Multireference Methods: Benchmarking on p
      Block Elements and Tentative Recommendations.
AB  - Within current electronic structure theory methods, fully relativistic four
      component (4c) approaches based on the Dirac Hamiltonian treat spin-orbit
      coupling with the most rigor. The spin treatment arises naturally from the
      formulation and does not need to be included ad hoc. Spin-orbit splittings can
      provide insightful benchmark criteria for the assessment of 4c methods; however,
      there have not been extensive studies in this respect. Spin-orbit splittings of
      the p-block elements B-I were computed using the 4c-CASSCF, 4c-CASPT2, and 4c-MR
      CISD+Q methods, as recently implemented in BAGEL, with uncontracted Dunning basis
      sets. Comparison with experiment reveals that the four-component methods yield
      good results, with most of the computed splittings falling within 15% of the
      experimental values. A large basis set is needed to obtain accurate splittings of
      the light elements B-F, while splittings of heavier elements show little basis
      dependence. The 4c-MR-CISD+Q method gave the best splittings for light elements,
      while 4c-CASSCF showed the best splittings for elements beyond fluorine. The 4c
      CASPT2 method gave the best splittings for group 13 atoms.

PMID- 29461829
TI  - Toward Accurate Conformational Energies of Smaller Peptides and Medium-Sized
      Macrocycles: MPCONF196 Benchmark Energy Data Set.
AB  - A carefully selected set of acyclic and cyclic model peptides and several other
      macrocycles, comprising 13 compounds in total, has been used to calibrate the
      accuracy of the DFT(-D3) method for conformational energies, employing BP86,
      PBE0, PBE, B3LYP, BLYP, TPSS, TPSSh, M06-2X, B97-D, OLYP, revPBE, M06-L, SCAN,
      revTPSS, BH-LYP, and omegaB97X-D3 functionals. Both high- and low-energy
      conformers, 15 or 16 for each compound adding to 196 in total, denoted as the
      MPCONF196 data set, were included, and the reference values were obtained by the
      composite protocol, yielding the CCSD(T)/CBS extrapolated energies or their DLPNO
      CCSD(T)/CBS equivalents in the case of larger systems. The latter was shown to be
      in near-quantitative (~0.10-0.15 kcal.mol-1) agreement with the canonical
      CCSD(T), provided the TightPNO setting is used, and, therefore, can be used as
      the reference for larger systems (likely up to 150-200 atoms) for the problem
      studied here. At the same time, it was found that many D3-corrected DFT
      functionals provide results of ~1 kcal.mol-1 accuracy, which we consider as quite
      encouraging. This result implies that DFT-D3 methods can be, for example, safely
      used in efficient conformational sampling algorithms. Specifically, the DFT
      D3/DZVP-DFT level of calculation seems to be the best trade-off between
      computational cost and accuracy. Based on the calculated data, we have not found
      any cheaper variant for the treatment of conformational energies, since the
      semiempirical methods (including DFTB) provide results of inferior accuracy
      (errors of 3-5 kcal.mol-1).

PMID- 29461830
TI  - Correction to "Effect of Monovalent Ion Parameters on Molecular Dynamics
      Simulations of G-Quadruplexes".

PMID- 29461831
TI  - Spin-Orbit Effects in the Spectroscopy of the X2Pi and a4Sigma- Electronic States
      of Carbon Iodide, CI.
AB  - Highly correlated ab initio calculations have been performed to describe the
      potential energy curves (PECs) and the spectroscopic properties of the X2Pi state
      and of the first excited state of the CI radical. Multi Reference configuration
      interaction calculations with Davidson correction (MRCI+Q) and relativistic
      effective core potential for the iodine atom have been performed. It is found
      that the two lowest electronic states, the X2Pi and the a4Sigma- states, are
      stable against dissociation and well separated from the other electronic states.
      Spectroscopic constants of these two states have been evaluated using their
      calculated PECs. Because of the presence of the iodine atom in this molecular
      system, spin-orbit (SO) interactions are playing an important role in the
      molecular and in the dissociation regions. The excitation energy of the a4Sigma-
      state is calculated 1.67 eV (MRCI) above the X2Pi ground state and 1.70/1.62 eV
      (MRCI with SO correction) for the Omega = 1/2 and 3/2 transitions, respectively.
      The dissociation energy D0 of the X2Pi ground state is evaluated 2.66 eV (MRCI
      calculation) without SO correction and 2.46/2.36 eV with SO correction for the
      Omega = 1/2 and 3/2 components, respectively. The dissociation energy D0 of the
      a4Sigma- state is evaluated 0.99 eV (MRCI calculation) without SO correction and
      0.83/0.72 eV with SO correction for the Omega = 1/2 and 3/2 components,
      respectively. This work should help for the identification of this radical in
      laboratory and in atmospheric media.

PMID- 29461832
TI  - Order, Disorder, and Temperature-Driven Compaction in a Designed Elastin Protein.
AB  - Artificial minielastin constructs have been designed that replicate the structure
      and function of natural elastins in a simpler context, allowing the NMR
      observation of structure and dynamics of elastin-like proteins with complete
      residue-specific resolution. We find that the alanine-rich cross-linking domains
      of elastin have a partially helical structure, but only when capped by proline
      rich hydrophobic domains. We also find that the hydrophobic domains, composed of
      prominent 6-residue repeats VPGVGG and APGVGV found in natural elastins, appear
      random coil by both NMR chemical shift analysis and circular dichroism. However,
      these elastin hydrophobic domains exhibit structural bias for a dynamically
      disordered conformation that is neither helical nor beta sheet with a degree of
      nonrandom structural bias which is dependent on residue type and position in the
      sequence. Another nonrandom-coil aspect of hydrophobic domain structure lies in
      the fact that, in contrast to other intrinsically disordered proteins, these
      hydrophobic domains retain a relatively condensed conformation whether attached
      to cross-linking domains or not. Importantly, these domains and the proteins
      containing them constrict with increasing temperature by up to 30% in volume
      without becoming more ordered. This property is often observed in nonbiological
      polymers and suggests that temperature-driven constriction is a new type of
      protein structural change that is linked to elastin's biological functions of
      coacervation-driven assembly and elastic recoil.

PMID- 29461833
TI  - A Systematic Exploration of Macrocyclization in Apelin-13: Impact on Binding,
      Signaling, Stability, and Cardiovascular Effects.
AB  - The apelin receptor generates increasing interest as a potential target across
      several cardiovascular indications. However, the short half-life of its cognate
      ligands, the apelin peptides, is a limiting factor for pharmacological use. In
      this study, we systematically explored each position of apelin-13 to find the
      best position to cyclize the peptide, with the goal to improve its stability
      while optimizing its binding affinity and signaling profile. Macrocyclic
      analogues showed a remarkably higher stability in rat plasma (half-life >3 h
      versus 24 min for Pyr-apelin-13), accompanied by improved affinity (analogue 15,
      Ki 0.15 nM and t1/2 6.8 h). Several compounds displayed higher inotropic effects
      ex vivo in the Langendorff isolated heart model in rats (analogues 13 and 15,
      maximum response at 0.003 nM versus 0.03 nM of apelin-13). In conclusion, this
      study provides stable and active compounds to better characterize the
      pharmacology of the apelinergic system.

PMID- 29461834
TI  - Exploiting the Inherent Photophysical Properties of the Major Tirapazamine
      Metabolite in the Development of Profluorescent Substrates for Enzymes That
      Catalyze the Bioreductive Activation of Hypoxia-Selective Anticancer Prodrugs.
AB  - Hypoxia-selective cytotoxins (HSCs) seek to exploit the oxygen-poor nature of
      tumor tissue for therapeutic gain. Typically, HSCs require activation by one
      electron bioreductive enzymes such as NADPH:cytochrome P450 reductase (CYPOR).
      Thus, successful clinical deployment of HSCs may be facilitated by the
      development and implementation of diagnostic probes that detect the presence of
      relevant bioreductive enzymes in tumor tissue. The work described here develops
      analogues of the well-studied HSC tirapazamine (3-amino-1,2,4-benzotriazine 1,4
      di- N-oxide, TPZ) as profluorescent substrates of the one-electron reductases
      involved in bioactivation of HSCs. Hypoxic metabolism of TPZ or 7-fluoro-TPZ by
      one-electron reductases releases inherently fluorescent mono- N-oxide metabolites
      that may serve as indicators, probes, markers, or stains for the detection of the
      enzymes involved in the bioactivation of HSCs. In particular, profluorescent
      compounds of this type can provide a foundation for fluorescence-based bioassays
      that help identify tumors responsive to HSCs.

PMID- 29461835
TI  - MS3-IDQ: Utilizing MS3 Spectra beyond Quantification Yields Increased Coverage of
      the Phosphoproteome in Isobaric Tag Experiments.
AB  - Protein phosphorylation is critically important for many cellular processes,
      including progression through the cell cycle, cellular metabolism, and
      differentiation. Isobaric labeling, for example, tandem mass tags (TMT), in
      phosphoproteomics workflows enables both relative and absolute quantitation of
      these phosphorylation events. Traditional TMT workflows identify peptides using
      fragment ions at the MS2 level and quantify reporter ions at the MS3 level.
      However, in addition to the TMT reporter ions, MS3 spectra also include fragment
      ions that can be used to identify peptides. Here we describe using MS3 spectra
      for both phosphopeptide identification and quantification, a process that we term
      MS3-IDQ. To maximize quantified phosphopeptides, we optimize several instrument
      parameters, including the modality of mass analyzer (i.e., ion trap or Orbitrap),
      MS2 automatic gain control (AGC), and MS3 normalized collision energy (NCE), to
      achieve the best balance of identified and quantified peptides. Our optimized MS3
      IDQ method included the following parameters for the MS3 scan: NCE = 37.5 and AGC
      target = 1.5 * 105, and scan range = 100-2000. Data from the MS3 scan were
      complementary to those of the MS2 scan, and the combination of these scans can
      increase phosphoproteome coverage by >50%, thereby yielding a greater number of
      quantified and accurately localized phosphopeptides.

PMID- 29461836
TI  - Predicting Catalytic Proton Donors and Nucleophiles in Enzymes: How Adding
      Dynamics Helps Elucidate the Structure-Function Relationships.
AB  - Despite the relevance of understanding structure-function relationships, robust
      prediction of proton donors and nucleophiles in enzyme active sites remains
      challenging. Here we tested three types of state-of-the-art computational methods
      to calculate the p Ka's of the buried and hydrogen bonded catalytic dyads in five
      enzymes. We asked the question what determines the p Ka order, i.e., what makes a
      residue proton donor vs a nucleophile. The continuous constant pH molecular
      dynamics simulations captured the experimental p Ka orders and revealed that the
      negative nucleophile is stabilized by increased hydrogen bonding and solvent
      exposure as compared to the proton donor. Surprisingly, this simple trend is not
      apparent from crystal structures and the static structure-based calculations.
      While the generality of the findings awaits further testing via a larger set of
      data, they underscore the role of dynamics in bridging enzyme structures and
      functions.

PMID- 29461837
TI  - Topological Electride Y2C.
AB  - Two-dimensional (2D) electrides are layered ionic crystals in which anionic
      electrons are confined in the interlayer space. Here, we report a discovery of
      nontrivial [Formula: see text] topology in the electronic structures of 2D
      electride Y2C. Based on first-principles calculations, we found a topological
      [Formula: see text] invariant of (1; 111) for the bulk band and topologically
      protected surface states in the surfaces of Y2C, signifying its nontrivial
      electronic topology. We suggest a spin-resolved angle-resolved photoemission
      spectroscopy (ARPES) measurement to detect the unique helical spin texture of the
      spin-polarized topological surface state, which will provide characteristic
      evidence for the nontrivial electronic topology of Y2C. Furthermore, the
      coexistence of 2D surface electride states and topological surface state enables
      us to explain the outstanding discrepancy between the recent ARPES experiments
      and theoretical calculations. Our findings establish a preliminary link between
      the electride in chemistry and the band topology in condensed-matter physics,
      which are expected to inspire further interdisciplinary research between these
      fields.

PMID- 29461839
TI  - Strain Stabilization of Superionicity in Copper and Lithium Selenides.
AB  - Superionic (SI) phases have utility as solid electrolytes for next generation
      battery technology, but these phases are typically not stable at room
      temperature. Our density functional theory calculations demonstrate that
      compressive lattice strain can stabilize SI phases of Cu2Se and Li2Se, two
      potential solid electrolytes. Electronic and bonding insights into this effect
      are obtained. In the ordered, non-SI phase, cations are localized primarily in
      tetrahedral (T) interstices with little access to the higher-energy octahedral
      (O) sites, but 1-2% compressive strain promotes attractive stabilization of the O
      cations with 6-fold coordination to Se anions, at the expense of the stability of
      4-fold-coordinated T cations. In such compressed lattices, cations can access
      both T and O sites, resulting in a cation-disordered, SI phase. Thus, lattice
      strain is demonstrated as a handle for controlling ionic structure and transport
      and accomplishing ambient temperature superionicity.

PMID- 29461838
TI  - Single-Layer Metasurface with Controllable Multiwavelength Functions.
AB  - In this paper, we report dispersion-engineered metasurfaces with distinct
      functionalities controlled by wavelength. Unlike previous approaches based on
      spatial multiplexing or vertical stacking of metasurfaces, we utilize a single
      phase profile with wavelength dependence encoded in the phase shifters'
      dispersion. We designed and fabricated a multiwavelength achromatic metalens
      (MAM) with achromatic focusing for blue (B), green (G), yellow (Y), and red (R)
      light and two wavelength-controlled beam generators (WCBG): one focuses light
      with orbital angular momentum (OAM) states ( l = 0,1,2) corresponding to three
      primary colors; the other produces ordinary focal spots ( l = 0) for red and
      green light, while generating a vortex beam ( l = 1) in the blue. A full color
      (RGB) hologram is also demonstrated in simulation. Our approach opens a path to
      applications ranging from near-eye displays and holography to compact
      multiwavelength beam generation.

PMID- 29461840
TI  - Enantioselective Copper-Catalyzed Methylboration of Alkenes.
AB  - An enantioselective Cu-catalyzed borylative cross-coupling reaction of alkenes,
      bis(pinacolato)diboron (B2(pin)2), and methyl iodide is reported. Alkenes
      including styrenes, beta-substituted styrenes, and challenging aliphatic olefins
      were smoothly transferred to the desired methylboration products with excellent
      diastereoselectivities (dr up to >99:1) and enantioselectivities (er up to 99:1).
      The utility of this process was demonstrated by the synthesis of naproxen and
      formal synthesis of two natural products.

PMID- 29461841
TI  - Synthesis of cis-5,5a,6,10b-Tetrahydroindeno[2,1-b]indoles through Palladium
      Catalyzed Decarboxylative Coupling of Vinyl Benzoxazinanones with Arynes.
AB  - A novel palladium-catalyzed decarboxylative coupling reaction of vinyl
      benzoxazinanones with arynes which may feature an intramolecular nucleophilic
      attack of an amino group at the central carbon of pi-allylpalladium intermediate
      has been developed. The cis-5,5a,6,10b-tetrahydroindeno[2,1-b]indoles were
      generated in moderate to good yields. One key to the success of the present
      reaction was to achieve comparable rates for the palladium-catalyzed
      decarboxylation and aryne formation steps.

PMID- 29461842
TI  - Lewis Base Passivation of Hybrid Halide Perovskites Slows Electron-Hole
      Recombination: Time-Domain Ab Initio Analysis.
AB  - Nonradiative electron-hole recombination plays a key role in determining photon
      conversion efficiencies in solar cells. Experiments demonstrate significant
      reduction in the recombination rate upon passivation of methylammonium lead
      iodide perovskite with Lewis base molecules. Using nonadiabatic molecular
      dynamics combined with time-domain density functional theory, we find that the
      nonradiative charge recombination is decelerated by an order of magnitude upon
      adsorption of the molecules. Thiophene acts by the traditional passivation
      mechanism, forcing electron density away from the surface. In contrast, pyridine
      localizes the electron at the surface while leaving it energetically near the
      conduction band edge. This is because pyridine creates a stronger coordinative
      bond with a lead atom of the perovskite and has a lower energy unoccupied orbital
      compared with thiophene due to the more electronegative nitrogen atom relative to
      thiophene's sulfur. Both molecules reduce two-fold the nonadiabatic coupling and
      electronic coherence time. A broad range of vibrational modes couple to the
      electronic subsystem, arising from inorganic and organic components. The
      simulations reveal the atomistic mechanisms underlying the enhancement of the
      excited-state lifetime achieved by the perovskite passivation, rationalize the
      experimental results, and advance our understanding of charge-phonon dynamics in
      perovskite solar cells.

PMID- 29461843
TI  - Coumarin[4]arene: A Fluorescent Macrocycle.
AB  - The pyranone functionalization of the upper rim of resorcinarene to provide the
      coumarin macrocycle called "coumarin[4]arene", possessing visible fluorescence
      and conformationally flexible behavior suitable for molecular recognition, has
      been successfully synthesized and characterized.

PMID- 29461844
TI  - Microscopic States and the Verwey Transition of Magnetite Nanocrystals
      Investigated by Nuclear Magnetic Resonance.
AB  - 57Fe nuclear magnetic resonance (NMR) of magnetite nanocrystals ranging in size
      from 7 nm to 7 MUm is measured. The line width of the NMR spectra changes
      drastically around 120 K, showing microscopic evidence of the Verwey transition.
      In the region above the transition temperature, the line width of the spectrum
      increases and the spin-spin relaxation time decreases as the nanocrystal size
      decreases. The line-width broadening indicates the significant deformation of
      magnetic structure and reduction of charge order compared to bulk crystals, even
      when the structural distortion is unobservable. The reduction of the spin-spin
      relaxation time is attributed to the suppressed polaron hopping conductivity in
      ferromagnetic metals, which is a consequence of the enhanced electron-phonon
      coupling in the quantum-confinement regime. Our results show that the magnetic
      distortion occurs in the entire nanocrystal and does not comply with the simple
      model of the core-shell binary structure with a sharp boundary.

PMID- 29461845
TI  - Wide Spectral Photoresponse of Layered Platinum Diselenide-Based Photodiodes.
AB  - Platinum diselenide (PtSe2) is a group-10 transition metal dichalcogenide (TMD)
      that has unique electronic properties, in particular a semimetal-to-semiconductor
      transition when going from bulk to monolayer form. We report on vertical hybrid
      Schottky barrier diodes (SBDs) of two-dimensional (2D) PtSe2 thin films on
      crystalline n-type silicon. The diodes have been fabricated by transferring large
      scale layered PtSe2 films, synthesized by thermally assisted conversion of
      predeposited Pt films at back-end-of-the-line CMOS compatible temperatures, onto
      SiO2/Si substrates. The diodes exhibit obvious rectifying behavior with a
      photoresponse under illumination. Spectral response analysis reveals a maximum
      responsivity of 490 mA/W at photon energies above the Si bandgap and relatively
      weak responsivity, in the range of 0.1-1.5 mA/W, at photon energies below the Si
      bandgap. In particular, the photoresponsivity of PtSe2 in infrared allows PtSe2
      to be utilized as an absorber of infrared light with tunable sensitivity. The
      results of our study indicate that PtSe2 is a promising option for the
      development of infrared absorbers and detectors for optoelectronics applications
      with low-temperature processing conditions.

PMID- 29461846
TI  - Ca2+-Signal Transduction Inhibitors, Kujiol A and Kujigamberol B, Isolated from
      Kuji Amber Using a Mutant Yeast.
AB  - A podocarpatriene and a labdatriene derivative, named kujiol A [13-methyl-8,11,13
      podocarpatrien-19-ol (1)] and kujigamberol B [15,20-dinor-5,7,9-labdatrien-13-ol
      (2)], respectively, were isolated from Kuji amber through detection with the aid
      of their growth-restoring activity against a mutant yeast strain ( zds1Delta
      erg3Delta pdr1Delta pdr3Delta), which is known to be hypersensitive with respect
      to Ca2+-signal transduction. The structures were elucidated by spectroscopic data
      analysis. Compounds 1 and 2 are rare organic compounds from Late Cretaceous
      amber, and the mutant yeast used seems useful for elucidating a variety of new
      compounds from Kuji amber specimens, produced before the K-Pg boundary.

PMID- 29461848
TI  - Leveraging benefit design for better diabetes self-management and A1C control.
AB  - OBJECTIVES: To evaluate the relationship between cost sharing for blood glucose
      testing strips and glycemic control rates. STUDY DESIGN: A retrospective
      observational study using medical and pharmacy claims data integrated with
      laboratory glycated hemoglobin (A1C) values for patients using insulin and
      testing strips. A new user study design was utilized to identify individuals from
      14 commercial US health plans who filled testing strips with assumed intention to
      monitor blood glucose. METHODS: Patients were divided into low (<20% of annual
      testing strip cost; n = 3575) and high (>=20%; n = 3580) cost-sharing categories.
      We compared the likelihood of patients in low and high cost-sharing categories
      achieving glycemic control (A1C <8.0%) through modified Poisson regression
      models. RESULTS: Patients with low cost sharing for testing strips had higher
      rates of control than those with high cost sharing (58.1% vs 50.3%; P <.001). Low
      cost sharing was associated with greater probability of glycemic control
      (adjusted risk ratio [aRR], 1.14; 95% CI, 1.09-1.20; P <.0001). Glycemic control
      was more likely for patients in areas with median household income greater than
      $60,000 versus less than $40,000 (aRR, 1.16; 95% CI, 1.07-1.25; P <.01) and
      greater than $80,000 versus less than $40,000 (aRR, 1.18; 95% CI, 1.06-1.32; P
      <.01). CONCLUSIONS: We found a statistically significant correlation between cost
      sharing for testing strips and better A1C control for patients using insulin
      medication. Lower cost sharing for testing strips can remove a barrier to
      diabetes self-management and may lead to improved glycemic control at the
      population level. Future efforts should study the potential benefits of reducing
      diabetic complications and associated cost savings.

PMID- 29461847
TI  - Dynamic associations between borderline personality disorder and stressful life
      events over five years in older adults.
AB  - The time course of borderline personality disorder (BPD) is far more variable
      than traditionally assumed. Shifting environmental conditions are theorized to
      account, at least in part, for fluctuations in symptom presentation over time. In
      the present study, we evaluated the reciprocal influences of stressful life
      events and borderline pathology in a representative community sample of 1,630
      older adults assessed 3 times over 5 years. An autoregressive cross-lagged model
      revealed strong, but imperfect, stability in symptoms of BPD over the study time
      frame. After adjusting for this continuity in BPD, the prospective effect of life
      stress on borderline pathology was virtually nil, contrary to expectations. On
      the other hand, borderline pathology was prospectively related to subsequent
      dependent event (i.e., stressors to which individuals may have contributed), but
      not independent event (i.e., fateful stressors), exposure. This pattern of
      associations was consistent with a stress generation effect. We conclude that
      stressful life events do not substantially redirect the trajectory of BPD in
      older adults, possibly owing to inertia of borderline pathology at this
      developmental stage. Instead, symptoms of BPD seem to promote stress exposure,
      thereby setting the stage for continued social impairment and comorbid
      psychiatric problems. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 29461849
TI  - Claims-based risk model for first severe COPD exacerbation.
AB  - OBJECTIVES: To develop and validate a predictive model for first severe chronic
      obstructive pulmonary disease (COPD) exacerbation using health insurance claims
      data and to validate the risk measure of controller medication to total COPD
      treatment (controller and rescue) ratio (CTR). STUDY DESIGN: A predictive model
      was developed and validated in 2 managed care databases: Truven Health MarketScan
      database and Reliant Medical Group database. This secondary analysis assessed
      risk factors, including CTR, during the baseline period (Year 1) to predict risk
      of severe exacerbation in the at-risk period (Year 2). METHODS: Patients with
      COPD who were 40 years or older and who had at least 1 COPD medication dispensed
      during the year following COPD diagnosis were included. Subjects with severe
      exacerbations in the baseline year were excluded. Risk factors in the baseline
      period were included as potential predictors in multivariate analysis.
      Performance was evaluated using C-statistics. RESULTS: The analysis included
      223,824 patients. The greatest risk factors for first severe exacerbation were
      advanced age, chronic oxygen therapy usage, COPD diagnosis type, dispensing of 4
      or more canisters of rescue medication, and having 2 or more moderate
      exacerbations. A CTR of 0.3 or greater was associated with a 14% lower risk of
      severe exacerbation. The model performed well with C-statistics, ranging from
      0.711 to 0.714. CONCLUSIONS: This claims-based risk model can predict the
      likelihood of first severe COPD exacerbation. The CTR could also potentially be
      used to target populations at greatest risk for severe exacerbations. This could
      be relevant for providers and payers in approaches to prevent severe
      exacerbations and reduce costs.

PMID- 29461850
TI  - Development of a tailored survey to evaluate a patient-centered initiative.
AB  - OBJECTIVES: Patient-centered care initiatives have proliferated, but assessing
      their effectiveness requires measures tailored to their likely effects. In this
      article, we describe the development and pilot testing of patient surveys used to
      assess change in patients' cancer care experiences over time in response to a
      patient-centered care initiative. STUDY DESIGN: Prospective case series. METHODS:
      Domains of patient-centered care were informed by the goals of the initiative and
      a review of existing tools. Items were selected and modified from 6 domains of
      validated or semivalidated instruments. Items were piloted with patients with
      cancer in waiting room settings to further assess the relevance and clarity of
      items, whether important concepts were missing, and acceptability regarding place
      and timing of the surveys and to estimate baseline top box scores (percentage of
      patients scoring an item the highest quality level) to minimize likely ceiling
      effects. The instrument was then administered to a consecutive sample of Stanford
      Cancer Center patients. Baseline item responses, Cronbach's alpha, and response
      bias were estimated. RESULTS: Items were modified based on patient feedback, top
      box scores, and reassessment of the domains. Over 6 months, 11,273 patients were
      surveyed, with a 49.7% response rate. Baseline top box scores ranged from 41.7%
      to 75.0% for any given item. Reliability and internal consistency were high for
      all domains (Cronbach's alpha >=0.80) except for the access domain. CONCLUSIONS:
      We developed reliable instruments to evaluate the essential elements of a patient
      centered care initiative at an academic medical center, which minimized patient
      burden and maximized the response rate.

PMID- 29461851
TI  - Impact of telephonic comprehensive medication reviews on patient outcomes.
AB  - OBJECTIVES: The majority of studies on medication therapy management (MTM) have
      focused on the conduct of in-person comprehensive medication reviews (CMRs).
      Although face-to-face MTM services may be the most well-known mode of delivery,
      there are other ways CMRs can be implemented as part of an MTM service.
      Specifically, telephonic CMR is an alternative method of offering MTM services
      that many patients may welcome. The purpose of this commentary was to highlight
      current findings regarding the impact of telephonic CMRs as a component of MTM
      services on health outcomes. STUDY DESIGN: Review of available literature
      analyzing the impact of telephonic CMRs on health outcomes. METHODS: PubMed was
      used to identify studies published between January 1980 and December 2016 using
      the search terms medication therapy management (MTM), telephonic MTM,
      comprehensive medication reviews, and targeted medication reviews. This search
      was limited to publications in English. Case reports were excluded. RESULTS: CMRs
      conducted telephonically as part of an MTM program may potentially reduce
      healthcare expenditures, hospitalizations, and mortality. CONCLUSIONS: Although
      study results have shown telephonic CMRs to be an effective way to enhance
      patient care and reduce healthcare expenditures, the components of telephonic MTM
      programs that make them most effective and the population on which they have the
      greatest impact are unknown. Moving forward, further evaluation of these programs
      is necessary to determine which specific factors, such as access to patient
      electronic health records, patient follow-up frequency, and the use of
      collaborative practice agreements, are most vital to improving patient outcomes.

PMID- 29461852
TI  - Variation in markups on outpatient oncology services in the United States.
AB  - OBJECTIVES: Price markups are a major cause of healthcare inflation and financial
      harm to patients, especially those who are self-paying or covered by commercial
      insurance. STUDY DESIGN: Retrospective analysis of publicly-available information
      on Medicare physician payments, representing 100% of Part B services provided to
      fee-for-service beneficiaries during calendar year 2014. METHODS: Outcomes were
      markup ratios for oncology services, defined as the ratio of submitted charges to
      the amount reimbursed by Medicare. For example, the overall cost-to-charge ratio
      for all Medicare-reimbursed services in 2013 was 3.4, or a 240% charge markup.
      RESULTS: Our analysis included oncology services provided by 3248 hospitals in
      all 50 states. There was significant variation in markup ratios by hospital
      across oncology specialty: radiology (median = 3.7; interquartile range [IQR],
      3.1-4.5), hematology/oncology (median = 2.3; IQR, 1.8-2.9), medical oncology
      (median = 2.4; IQR, 1.8-3.0), pathology (median = 4.1; IQR 3.1-5.1), and
      radiation oncology (median = 3.6; IQR, 2.9-4.5). Higher markups were associated
      with for-profit status for medical oncology services (coefficient, 0.29; 95% CI,
      0.12-0.45) and prestige status for radiology (0.53; 95% CI, 0.15-0.92) and
      pathology (0.65; 95% CI, 0.20-1.09) services. CONCLUSIONS: High markups exist for
      oncology services, and further legislation is needed to protect patients from
      highly variable pricing and to address disparities in access to high-quality
      cancer care.

PMID- 29461853
TI  - Community navigators reduce hospital utilization in super-utilizers.
AB  - OBJECTIVES: Super-utilizers place a significant burden on the healthcare system.
      Blending the roles of patient navigators and community health workers may address
      the clinical and social needs of these patients. This study evaluated the
      effectiveness of community navigators in reducing hospital utilization and costs
      among super-utilizers from a low-income area in Memphis, Tennessee. STUDY DESIGN:
      Controlled pre-post (difference-in-differences [DID]) design using Methodist Le
      Bonheur Healthcare electronic health records from 2013 to 2016. METHODS: Data
      were abstracted for 1 year pre- and post intervention for super-utilizers working
      with a community navigator (n = 159) and a control group of similar super
      utilizers (n = 280). We compared utilization (hospital encounters, total hospital
      days, days between encounters, 30-day readmissions) and costs before and after
      working with a navigator for the intervention group with utilization and costs in
      a control group not working with a navigator and compared relative changes using
      a DID approach. RESULTS: Utilization and cost outcomes for intervention and
      control groups declined significantly from the pre- to postintervention periods.
      Relative to the control group, super-utilizers working with community navigators
      had an additional 13% reduction in hospital encounters (95% CI, -19% to -6%), 8%
      reduction in total hospital days (95% CI, -14% to -2%), and 9% increase in days
      between encounters (95% CI, 4%-15%). The intervention group also had additional
      reductions in 30-day readmissions (-18%; 95% CI, -44% to 22%) and costs (-$4903;
      95% CI, -$13,579 to $3774), but these were not statistically significant.
      CONCLUSIONS: Community navigators can reduce subsequent hospital utilization in
      super-utilizers. Expansions of this model should examine the model's
      effectiveness in other populations and outcomes.

PMID- 29461854
TI  - Data breach locations, types, and associated characteristics among US hospitals.
AB  - OBJECTIVES: The objectives of this study were to describe the locations in
      hospitals where data are breached, the types of breaches that occur most often at
      hospitals, and hospital characteristics, including health information technology
      (IT) sophistication and biometric security capabilities, that may be predicting
      factors of large data breaches that affect 500 or more patients. STUDY DESIGN:
      The Office of Civil Rights breach data from healthcare providers regarding
      breaches that affected 500 or more individuals from 2009 to 2016 were linked with
      hospital characteristics from the Health Information Management Systems Society
      and the American Hospital Association Health IT Supplement databases. METHODS:
      Descriptive statistics were used to characterize hospitals with and without
      breaches, data breach type, and location/mode of data breaches in hospitals.
      Multivariate logistic regression analysis explored hospital characteristics that
      were predicting factors of a data breach affecting at least 500 patients,
      including area characteristics, region, health system membership, size, type,
      biometric security use, health IT sophistication, and ownership. RESULTS: Of all
      types of healthcare providers, hospitals accounted for approximately one-third of
      all data breaches and hospital breaches affected the largest number of
      individuals. Paper and films were the most frequent location of breached data,
      occurring in 65 hospitals during the study period, whereas network servers were
      the least common location but their breaches affected the most patients overall.
      Adjusted multivariate results showed significant associations among data breach
      occurrences and some hospital characteristics, including type and size, but not
      others, including health IT sophistication or biometric use for security.
      CONCLUSIONS: Hospitals should conduct routine audits to allow them to see their
      vulnerabilities before a breach occurs. Additionally, information security
      systems should be implemented concurrently with health information technologies.
      Improving access control and prioritizing patient privacy will be important steps
      in minimizing future breaches.

PMID- 29461855
TI  - ACA Marketplace premiums and competition among hospitals and physician practices.
AB  - OBJECTIVES: To examine the association between annual premiums for health plans
      available in Federally Facilitated Marketplaces (FFMs) and the extent of
      competition and integration among physicians and hospitals, as well as the number
      of insurers. STUDY DESIGN: We used observational data from the Center for
      Consumer Information and Insurance Oversight on the annual premiums and other
      characteristics of plans, matched to measures of physician, hospital, and insurer
      market competitiveness and other characteristics of 411 rating areas in the 37
      FFMs. METHODS: We estimated multivariate models of the relationship between
      annual premiums and Herfindahl-Hirschman indices of hospitals and physician
      practices, controlling for the number of insurers, the extent of physician
      hospital integration, and other plan and rating area characteristics. RESULTS:
      Premiums for Marketplace plans were higher in rating areas in which physician,
      hospital, and insurance markets were less competitive. An increase from the 10th
      to the 90th percentile of physician concentration and hospital concentration was
      associated with increases of $393 and $189, respectively, in annual premiums for
      the Silver plan with the second lowest cost. A similar increase in the number of
      insurers was associated with a $421 decrease in premiums. Physician-hospital
      integration was not significantly associated with premiums. CONCLUSIONS: Premiums
      for FFM plans were higher in markets with greater concentrations of hospitals and
      physicians but fewer insurers. Higher premiums make health insurance less
      affordable for people purchasing unsubsidized coverage and raise the cost of
      Marketplace premium tax credits to the government.

PMID- 29461856
TI  - Cost-effectiveness of collaborative care for depression and PTSD in military
      personnel.
AB  - OBJECTIVES: Collaborative care is an effective approach for treating
      posttraumatic stress disorder (PTSD) and depression within the US Military Health
      System (MHS), but its cost-effectiveness remains unstudied. Our objective was to
      evaluate the costs and cost-effectiveness of centrally assisted collaborative
      telecare (CACT) versus optimized usual care (OUC) for PTSD and depression in the
      MHS. STUDY DESIGN: A randomized trial compared CACT with OUC. Routine primary
      care screening identified active-duty service members with PTSD or depression.
      Eligible participants (N = 666) were randomized to CACT or OUC and assessed at 3,
      6, and 12 months. OUC patients could receive care management and increased
      behavioral health support. CACT patients could receive these services plus
      stepped psychosocial treatment and routine centralized team monitoring. METHODS:
      Quality-adjusted life-years (QALYs) were derived from the 12-Item Short Form
      Health Survey. Claims and case management data were used to estimate costs. Cost
      effectiveness analyses were conducted from a societal perspective. RESULTS: Data
      from 629 patients (320 CACT and 309 OUC) with sufficient follow-up were analyzed.
      CACT patients gained 0.02 QALYs (95% CI, -0.001 to 0.03) relative to OUC
      patients. Twelve-month costs, including productivity, were $987 (95% CI, -$3056
      to $5030) higher for CACT versus OUC. CACT was estimated to cost $49,346 per QALY
      gained compared with OUC over 12 months. There is a 58% probability that CACT is
      cost-effective at a $100,000/QALY threshold. CONCLUSIONS: Despite its higher
      costs, CACT appears to be a cost-effective strategy relative to OUC for managing
      PTSD and depression in the MHS.

PMID- 29461857
TI  - Pricing of monoclonal antibody therapies: higher if used for cancer?
AB  - OBJECTIVES: The rising prices of specialty drugs have prompted a debate about how
      medications are priced. With the average price of cancer drugs doubling in the
      last decade, the unsustainability of drug prices is especially concerning in
      oncology and hematology. The objective of this study was to compare the prices of
      monoclonal antibodies (mAbs) approved in the last 20 years by the FDA across
      disease states. STUDY DESIGN: We identified all indications approved by the FDA
      for mAbs from 1997 to 2016 and calculated the annual price of 1-year treatment
      for each mAb-indication combination as the product of the US average wholesale
      price per milligram and the recommended dose. METHODS: We compared the annual
      price of treatment with each mAb across disease states using generalized linear
      models with gamma distribution and log link, controlling for route of
      administration, chemical structure, source, and time since FDA approval. RESULTS:
      The average annual price of a mAb was $96,731, exceeding $100,000 for 34 mAb
      indication combinations. Oncology and hematology mAbs represented 40% of the mAb
      indication combinations approved, yet they accounted for more than 85% of those
      priced $100,000 or higher. After adjusting for factors that can affect production
      costs, the annual price of oncology or hematology mAbs was $149,622 higher than
      those used in cardiovascular or metabolic disorders; $98,981 higher than in
      immunology; $128,856 higher than in infectious diseases or allergy; and $106,830
      higher than in ophthalmology (all P <.001). CONCLUSIONS: The annual price of mAb
      therapies is about $100,000 higher in oncology and hematology than in other
      disease states.

PMID- 29461858
TI  - Effect of Meridian Acupressure on Aerobic Performance of Healthy Young
      Population: A Randomized Controlled Study.
AB  - OBJECTIVES: An enhancement of aerobic capacity has always been in the scope of
      various exercise programs. Apart from traditional, like endurance training,
      methods to improve aerobic performance, there is growing interest to alternative
      bodywork techniques, like massage, yoga, and acupuncture. This study aimed to
      investigate the acupressure effect on maximal aerobic capacity (VO2max) in
      healthy young adult males. DESIGN: Forty young healthy participants were randomly
      divided into intervention (n = 20) and control (n = 20) groups. The inferred
      VO2max level in groups was assessed by the 6-min Harvard step test twice: at
      baseline and after acupressure session. INTERVENTION: Three-minute finger-tip
      point massage of Neiguan, Juque, and Xinshu acupoints covered by 1 cm2 sticky
      capsaicin-dressed heat plasters was applied in the intervention group, whereas in
      the control group, placebo acupressure was utilized. RESULTS: The inferred VO2max
      in the intervention group increased from baseline 2.38 +/- 0.48 L/min to 2.57 +/-
      0.6 L/min (p < 0.003), whereas inferred VO2max of the control group remained
      unchanged (2.46 +/- 0.5 L/min at baseline and 2.47 +/- 0.4 L/min after placebo
      acupressure, p > 0.9). CONCLUSIONS: The results of the study demonstrated that
      finger-tip acupressure increases aerobic performance of young healthy males on
      more than 10%. Acupressure probably decreased anxiety level, which allowed better
      utilization of available energy sources.

PMID- 29461859
TI  - Epidemic Thunderstorm Asthma Protection with Five-Grass Pollen Tablet Sublingual
      Immunotherapy: A Clinical Trial.

PMID- 29461860
TI  - Nonsteroidal Antiinflammatory Drug Use and Clinical Outcomes of Community
      acquired Pneumonia.

PMID- 29461861
TI  - Measurement properties of the Chinese version of the Mental Fatigue Scale for
      patients with traumatic brain injury.
AB  - OBJECTIVES: To translate the Mental Fatigue Scale into a Chinese version (CMFS),
      to develop a more valid and precise CMFS by using an item response theory-based
      model, and to examine the reliability and validity of the CMFS. METHODS: One
      hundred and fifty adults having traumatic brain injury for at least 6 months were
      included. Each participant completed a battery of questionnaires (i.e. the
      Chinese version of the Chalder Fatigue Scale [ChCFS], Chinese version of the
      Clinically Useful Depression Outcome Scale [CUDOS-Chinese], and CMFS). Two
      parameter graded response models were used to evaluate the location and
      discrimination performance of the CMFS. The reliability and validity of the CMFS
      were also evaluated. RESULTS: One item investigating 'increased sleep at night'
      (item 14) was removed because it had a low discrimination value (0.86) and
      provided less information. The internal consistency and test-retest reliability
      of the 13-item CMFS were high (0.92 and 0.96, respectively). The CMFS score was
      positively correlated with the ChCFS and the CUDOS-Chinese scores (r = 0.77 and
      0.80, respectively). CONCLUSION: The CMFS provides reliable and valid information
      on mental fatigue for future research and clinical practice involving patients
      with traumatic brain injury.

PMID- 29461862
TI  - Superbubbles, Ultrabubbles, and Cacti.
AB  - A superbubble is a type of directed acyclic subgraph with single distinct source
      and sink vertices. In genome assembly and genetics, the possible paths through a
      superbubble can be considered to represent the set of possible sequences at a
      location in a genome. Bidirected and biedged graphs are a generalization of
      digraphs that are increasingly being used to more fully represent genome assembly
      and variation problems. In this study, we define snarls and ultrabubbles,
      generalizations of superbubbles for bidirected and biedged graphs, and give an
      efficient algorithm for the detection of these more general structures. Key to
      this algorithm is the cactus graph, which, we show, encodes the nested
      decomposition of a graph into snarls and ultrabubbles within its structure. We
      propose and demonstrate empirically that this decomposition on bidirected and
      biedged graphs solves a fundamental problem by defining genetic sites for any
      collection of genomic variations, including complex structural variations,
      without need for any single reference genome coordinate system. Further, the
      nesting of the decomposition gives a natural way to describe and model variations
      contained within large variations, a case not currently dealt with by existing
      formats [e.g., variant cell format (VCF)].

PMID- 29461863
TI  - Home parenteral nutrition for patients with intestinal failure due to advanced
      cancer.
AB  - Patients who experience intestinal failure as a result of advanced malignancy can
      be supported with parenteral nutrition in their own home (HPN). This article
      describes how to identify which cancer patients would benefit from this therapy
      and how to ensure it is safely and correctly administered in the home setting.

PMID- 29461864
TI  - Ectopic Expression of JcWRKY Confers Enhanced Resistance in Transgenic Tobacco
      Against Macrophomina phaseolina.
AB  - Plants possess an innate immune system comprising of a complex network of closely
      regulated defense responses involving differential gene expression mediated by
      transcription factors (TFs). The WRKYs comprise of an important plant-specific TF
      family, which is involved in regulation of biotic and abiotic defenses. The
      overexpression of JcWRKY resulted in improved resistance in transgenic tobacco
      against Macrophomina phaseolina. The production of reactive oxygen species (ROS)
      and its detoxification through antioxidative system in the transgenics
      facilitates defense against Macrophomina. The enhanced catalase activity on
      Macrophomina infection limits the spread of infection. The transcript expression
      of antioxidative enzymes gene (CAT and SOD) and salicylic acid (SA) biosynthetic
      gene ICS1 showed upregulation during Macrophomina infection and combinatorial
      stress. The enhanced transcript of pathogenesis-related genes PR-1 indicates the
      accumulation of SA during different stresses. The PR-2 and PR-5 highlight the
      activation of defense responses comprising of activation of hydrolytic cleavage
      of glucanases and thaumatin-like proteins causing disruption of fungal cells. The
      ROS homeostasis in coordination with signaling molecules regulate the defense
      responses and inhibit fungal growth.

PMID- 29461865
TI  - Validation of auditory detection response task method for assessing the
      attentional effects of cognitive load.
AB  - OBJECTIVES: There are 3 standardized versions of the Detection Response Task
      (DRT), 2 using visual stimuli (remote DRT and head-mounted DRT) and one using
      tactile stimuli. In this article, we present a study that proposes and validates
      a type of auditory signal to be used as DRT stimulus and evaluate the proposed
      auditory version of this method by comparing it with the standardized visual and
      tactile version. METHODS: This was a within-subject design study performed in a
      driving simulator with 24 participants. Each participant performed 8 2-min-long
      driving sessions in which they had to perform 3 different tasks: driving,
      answering to DRT stimuli, and performing a cognitive task (n-back task). Presence
      of additional cognitive load and type of DRT stimuli were defined as independent
      variables. DRT response times and hit rates, n-back task performance, and pupil
      size were observed as dependent variables. RESULTS: Significant changes in pupil
      size for trials with a cognitive task compared to trials without showed that
      cognitive load was induced properly. Each DRT version showed a significant
      increase in response times and a decrease in hit rates for trials with a
      secondary cognitive task compared to trials without. Similar and significantly
      better results in differences in response times and hit rates were obtained for
      the auditory and tactile version compared to the visual version. There were no
      significant differences in performance rate between the trials without DRT
      stimuli compared to trials with and among the trials with different DRT stimuli
      modalities. CONCLUSIONS: The results from this study show that the auditory DRT
      version, using the signal implementation suggested in this article, is sensitive
      to the effects of cognitive load on driver's attention and is significantly
      better than the remote visual and tactile version for auditory-vocal cognitive (n
      back) secondary tasks.

PMID- 29461866
TI  - The Prognostic Value of Combinations of Genetic Polymorphisms in the ITGB3,
      ITGA2, and CYP2C19*2 Genes in Predicting Cardiovascular Outcomes After Coronary
      Bypass Grafting.
AB  - AIM: To determine if there are any associations between the single nucleotide
      polymorphisms (SNPs): rs2046934, rs1126643, rs5918, rs6065, rs4244285; rs4986893
      and the occurrence of cardiovascular events (CVE) in patients following coronary
      artery bypass grafting (CABG) surgery. MATERIALS AND METHODS: The study included
      130 CABG patients with stable angina grades II-IV. After CABG 69 of the patients
      were treated with acetylsalicylic acid (ASA) alone, and 61 received dual
      antiplatelet therapy (ASA+clopidogrel). Platelet function was assessed by light
      transmission aggregometry with adenosinediphosphate and arachidonic acid. The
      SNPs were identified by real-time polymerase chain reaction (PCR) with
      electrophoretic detection. The mean follow-up period was equal to 10.9 +/- 5.2
      months. The primary end point included the composite of all-cause mortality,
      myocardial infarction (MI), and ischemic stroke. RESULTS: During the follow-up
      period 12 CVE were registered: 3 deaths, 6 MI, 3 strokes. Patients with composite
      mutant alleles of ITGB3+CYP2C19*2 or CYP2C19*2 + ITGA2, and with the mutant
      allele (*2) of CYP2C19, met end points more often than patients with other gene
      combinations (wild-type homozygotes, presence of one mutant allele of ITGB3 or
      ITGA2, the composite of mutant alleles of ITGB3+ITGA2 or ITGB3+ITGA2+CYP2C19*2;
      hazard ratio = 4, 95% confidence interval: 2.19-7.29, p = 0.008). CONCLUSION:
      Carriage of a combination of mutant alleles in multiple genes including
      ITGB3+CYP2C19*2 or CYP2C19*2 + ITGA2 or CYP2C19*2 are possible predictors of CVE
      in patients after CABG.

PMID- 29461867
TI  - Associations Between Three CTLA-4 Polymorphisms and Hashimoto's Thyroiditis Risk:
      An Updated Meta-Analysis with Trial Sequential Analysis.
AB  - AIMS: In this article, we conducted an updated meta-analysis with trial
      sequential analysis (TSA) to refine the associations between three common single
      nucleotide polymorphisms (SNPs) in the CTLA-4 gene (+49A/G, CT60, and -318C/T)
      and Hashimoto's thyroiditis (HT). METHODS: Statistical association analyses were
      performed using four genetic models, including the allelic, codominant, dominant,
      and recessive models with the Revman 5.3, Stata 14.0, and TSA 0.9 software. For
      quality evaluation, the Newcastle-Ottawa Scale was used. RESULTS: Our meta
      analysis included 29 independent studies with low risk of bias that involved 3614
      cases and 8839 controls. The pooled results indicated a significant association
      between the +49A/G polymorphism and an increased risk of HT in all four genetic
      models. Furthermore, the TSA demonstrated that the evidence of this association
      was robust and credible. Subgroup analysis revealed a significantly higher risk
      of HT in Asians compared with Caucasians associated with the +49A/G polymorphism.
      Surprisingly, in contrast to the results with adults, we did not find any
      significant association when analyzing the pediatric subgroup. For the CT60
      polymorphism, a significant association with risk of HT was detected overall, and
      subgroup analysis revealed that this association was significant in the Asian
      subgroup, but not in the Caucasian subgroup. No statistically significant
      associations were detected in any of the investigated genetic models for the 
      318C/T polymorphism. However, the results of the TSA suggested that the sample
      sizes used for the CTLA-4 CT60 and -318C/T SNPs were insufficient. CONCLUSION:
      Our meta-analysis showed significant associations between the risk of HT and both
      the +49A/G and CT60 polymorphisms, but not the -318C/T polymorphism. In addition,
      the TSA results indicated that CTLA-4 +49A/G should be considered as a biomarker
      for HT, whereas both the CT60 and -318C/T SNPs warrant confirmation by further
      studies.

PMID- 29461868
TI  - Genome-wide identification, characterization, and transcriptional analysis of the
      metacaspase gene family in cucumber (Cucumis sativus).
AB  - Metacaspase (MC), a family of caspase-like proteins, plays vital roles in
      regulating programmed cell death (PCD) during development and in response to
      stresses in plants. In this study, five MC genes (designated as CsMC1 to CsMC5)
      were identified in the cucumber (Cucumis sativus) genome. Sequence analysis
      revealed that CsMC1-CsMC3 belong to type I MC proteins, while CsMC4 and CsMC5 are
      type II MC proteins. Phylogenetic tree and conserved motif analysis of MC
      proteins indicated that these proteins can be classified into two groups, which
      are correlated with the types of these MC proteins. Gene structure analysis
      demonstrated that type I CsMC genes contain 4-7 introns, while all type II CsMC
      genes harbor one intron. In addition, many hormone-, stress-, and development
      related cis-elements were identified in the promoter regions of CsMC genes.
      Expression analysis using RNA-seq data revealed that CsMC genes have distinct
      expression patterns in various tissues and developmental stages. qRT-PCR results
      showed that the transcript levels of CsMC genes could be regulated by various
      abiotic stresses such as NaCl, PEG, and cold. These results demonstrate that the
      cucumber MC gene family may function in tissue development and plant stress
      responses.

PMID- 29461869
TI  - Volcanogenic Pseudo-Fossils from the ~3.48 Ga Dresser Formation, Pilbara, Western
      Australia.
AB  - The ~3.48 billion-year-old Dresser Formation, Pilbara Craton, Western Australia,
      is a key geological unit for the study of Earth's earliest life and the habitats
      it occupied. Here, we describe a new suite of spheroidal to lenticular
      microstructures that morphologically resemble some previously reported Archean
      microfossils. Correlative microscopy shows that these objects have a size
      distribution, wall ultrastructure, and chemistry that are incompatible with a
      microfossil origin and instead are interpreted as pyritized and silicified
      fragments of vesicular volcanic glass. Organic kerogenous material is associated
      with much of the altered volcanic glass; variable quantities of organic carbon
      line or fill the insides of some individual vesicles, while relatively large,
      tufted organic-rich laminae envelop multiple vesicles. The microstructures
      reported herein constitute a new type of abiogenic artifact (pseudo-fossil) that
      must be considered when evaluating potential signs of early life on Earth or
      elsewhere. In the sample studied here, where hundreds of these microstructures
      are present, the combined evidence permits a relatively straightforward
      interpretation as vesicular volcanic glass. However, reworked, isolated, and
      silicified microstructures of this type may prove particularly problematic in
      early or extraterrestrial life studies since they adsorb carbon onto their
      surfaces and are readily pyritized, mimicking a common preservation mechanism for
      bona fide microfossils. In those cases, nanoscale analysis of wall ultrastructure
      would be required to firmly exclude a biological origin. Key Words: Microfossils
      Pseudo-fossils-Volcanic vesicles-Archean life-Pilbara Craton-Dresser Formation.
      Astrobiology 18, 539-555.

PMID- 29461870
TI  - Randomized, double-blind, crossover study of the adhesiveness of two formulations
      of rotigotine transdermal patch in patients with Parkinson's disease.
AB  - OBJECTIVE: In patch-based transdermal drug delivery, adhesiveness is critical for
      safe and effective treatment, especially in Parkinson's disease (PD) where
      excessive sweating is common. This study compared the adhesiveness of two
      transdermal patch formulations of rotigotine (improved room temperature-stable
      [PR2.3.1/Treatment A] and intermediate cold storage product [PR2.1.1/Treatment
      B]), using the largest patch size (40 cm2). METHODS: PD0018 (NCT02230904) was a
      multicenter, randomized, double-blind, crossover study. PD patients received
      Treatments A and B in randomized order for 2 days each. Patch adhesiveness was
      measured immediately after patch application and 24 hours thereafter (before
      removal). Primary variable: change in average investigator-rated adhesiveness
      score between treatments, per modified European Medicines Agency scale
      (EMA/CHMP/QWP/911254/2011, 2012). RESULTS: Fifty-seven patients were randomized;
      56 patients completed the study. Five patients were excluded from analysis for
      accidental unblinding. Treatment A had better average adhesiveness score (mean +/
      SD Treatment A - Treatment B: 1.115 +/- 1.635). A higher percentage of patients
      on both days had patch adhesiveness >=95% at 24 hours for Treatment A (first day:
      65.4%, second day: 71.2%) vs. Treatment B (46.2%, 36.5%), and were satisfied with
      patch adhesiveness of Treatment A (first day: 75.0%, second day: 73.1%) vs.
      Treatment B (65.4%, 59.6%). Average patch-wear duration was similar between
      formulations (23.761 hours vs. 23.495 hours per patch). Both formulations were
      well tolerated with no new safety observations. CONCLUSION: Results indicated
      greater adhesiveness for the improved room temperature-stable formulation
      (PR2.3.1) vs. intermediate cold storage product (PR2.1.1) using the largest patch
      size, with comparable safety and skin tolerability.

PMID- 29461871
TI  - Continuous, comprehensive and crucial care: The role of the CNS in the metastatic
      castration-resistant prostate cancer patient pathway.
AB  - Several treatment options are now available to men with metastatic castration
      resistant prostate cancer (mCRPC). While survival rates for mCRPC continue to
      improve, patients are faced with increasingly complex treatment pathways and
      decisions. The clinical nurse specialist (CNS) plays a crucial role in navigating
      patients with mCRPC through their treatment pathway and fulfils a number of key
      responsibilities, including providing holistic care and support to patients and
      their families, educating and communicating with them in a timely and effective
      manner, and liaising with other healthcare professionals to seamlessly coordinate
      patient treatment. However, increasing patient caseloads and administrative
      duties are leaving CNSs with little time to fulfil their supportive role.
      Additional resources are needed in order to both promote and preserve this
      supportive role, thus ensuring that mCRPC patients receive the best possible
      care.

PMID- 29461872
TI  - Patients' Attitudes Towards the Return of Incidental Findings After Research with
      Residual Tissue: A Mixed Methods Study.
AB  - AIMS: To investigate the attitudes of patients toward the return of individual
      research results from scientific research with residual tissue. METHODS AND
      FINDINGS: We recruited 1319 patients from 6 Dutch hospitals. In total, 673
      patients (51% response rate) completed the questionnaire and 146 were
      interviewed. Based on the questionnaire data, the majority of respondents (92%)
      wanted to be informed of incidental findings about both a curable (92%) and an
      incurable (76%) disease. Respondents' wishes to be informed about incidental
      findings did not vary significantly as a function of patient demographics or type
      of disease. The interview data show that respondents wished to be informed about
      incidental findings because they considered it to be normal practice; they
      expected the information to be of benefit for their health. Information should be
      provided by their physician. Yet, most respondents (84%) would consent to
      research even if they would not be informed about incidental findings, primarily
      because they recognized that there might be practical problems in providing such
      information, and because they valued scientific research highly. CONCLUSIONS: We
      conclude that, while the majority of patients want to be informed about
      incidental findings, they also recognize that this may be difficult.

PMID- 29461874
TI  - Grohar: Automated Visualization of Genome-Scale Metabolic Models and Their
      Pathways.
AB  - Genome-scale metabolic models (GEMs) have become a powerful tool for the
      investigation of the entire metabolism of the organism in silico. These models
      are, however, often extremely hard to reconstruct and also difficult to apply to
      the selected problem. Visualization of the GEM allows us to easier comprehend the
      model, to perform its graphical analysis, to find and correct the faulty
      relations, to identify the parts of the system with a designated function, etc.
      Even though several approaches for the automatic visualization of GEMs have been
      proposed, metabolic maps are still manually drawn or at least require large
      amount of manual curation. We present Grohar, a computational tool for automatic
      identification and visualization of GEM (sub)networks and their metabolic fluxes.
      These (sub)networks can be specified directly by listing the metabolites of
      interest or indirectly by providing reference metabolic pathways from different
      sources, such as KEGG, SBML, or Matlab file. These pathways are identified within
      the GEM using three different pathway alignment algorithms. Grohar also supports
      the visualization of the model adjustments (e.g., activation or inhibition of
      metabolic reactions) after perturbations are induced.

PMID- 29461873
TI  - Identification of the Functional Autophagy-Regulatory Domain in HCLS1-Associated
      Protein X-1 That Resists Against Oxidative Stress.
AB  - HCLS1 Associated Protein X-1 (HAX1) promotes cell survival through attenuation of
      the damaged signals from endoplasmic reticulum and mitochondria, which are known
      as prominent intracellular compartments for the autophagic process under stress
      conditions. This study investigates whether autophagy can be upregulated in
      response to HAX1 overexpression and identifies the functional motif in HAX1
      responsible for the autophagic induction. Autophagosome accumulation,
      mitochondrial membrane potential (Deltapsim), and apoptosis were assessed in
      HEK293 cells post transduction with full-length or truncated HAX1-encoding genes,
      while empty vector-transduced cells served as control. Upon the oxidative stress,
      the enhanced autophagy induction was observed in cells overexpressing HAX1, as
      well as HAX1 truncations that encode peptide segments ranging from amino acids
      127-180 (AA127-180). This protective response was further supported by flow
      cytometry and Western Blot results, in which oxidative stress-induced Deltapsim
      dissipation and the programmed cell death were suppressed in HAX1-overexpressing
      cells, associated with reduced DNA fragmentation and decreased Caspase-9
      cleavage. Interestingly, the HAX1-induced autophagy response was abrogated when
      AA127-180 was removed, compromising the antiapoptotic effects upon oxidative
      stress. Overall, these data indicate that autophagy induction is involved in HAX1
      induced cell protective mechanism, and AA127-180 serves as the functional
      autophagy-regulatory domain of this antiapoptotic protein.

PMID- 29461875
TI  - Assessing adherence to inhaled medication in asthma: Impact of once-daily versus
      twice-daily dosing frequency. The ATAUD study.
AB  - INTRODUCTION: This study was aimed at evaluating whether once-daily regimens (od
      r) show benefits in adherence when compared to twice-daily (td-r). METHODS:
      Prospective, multicenter, 6-month follow-up study with two visits. The main
      objective was to compare adherence assessed by the electronic prescription refill
      rate (EPRR) and by the 10-item Test of Adherence to Inhalers (TAI) in patients
      with od-r and td-r. Suboptimal adherence was defined as TAI < 50 or EPRR <= 80%.
      The effect of suboptimal adherence on meaningful clinical outcomes and the
      concordance between EPRR and TAI were also examined. RESULTS: One hundred and
      ninety-seven patients (47.3 +/- 15.9 years, 65% women) were included and 180
      completed the study. TAI score was <50 in 29.8% od-r patients and 46.9% in td-r
      (p = 0.01) and EPRR was <=80% in 22.6% and 37.5% respectively (p = 0.02). The
      correlation between the two methods was moderate (rho = 0.548; p < 0.001). There
      were no significant differences in FEV1 (%), symptoms or exacerbations between
      patients with optimal and suboptimal adherence. During follow-up, five patients
      (6%) with o-dr and 17 patients (17.7%) with t-dr suffered an exacerbation (p =
      0.013). At visit two, 13.1% of the patients with o-dr and 31.3% with t-dr had
      uncontrolled asthma (p = 0.003), although more patients with o-dr were receiving
      inhaled corticosteroids in the high-dose stratum (25.8% vs. 11.5%; p = 0.001).
      CONCLUSION: Mean adherence rates were greater with od-r than with td-r, but we
      did not observe an effect on clinical outcomes.

PMID- 29461876
TI  - Voice Quality in Adults Treated for Unilateral Cleft Lip and Palate: Long-term
      Follow-up After 1- or 2-Stage Palate Repair.
AB  - OBJECTIVES: The aim of the current study was to assess voice quality among adults
      treated for unilateral cleft lip and palate (UCLP), after 1- or 2-stage palate
      closure, and compare it to a noncleft control group. STUDY DESIGN: Cross
      sectional study in UCLP patients with long-term follow-up and noncleft controls.
      PARTICIPANTS: UCLP patients born 1960-1987, treated at Uppsala University
      Hospital, Sweden, were examined (n = 73) at a mean of 35 years after primary
      surgery. Forty-seven patients (64%) had been treated with 1-stage palate closure
      and 26 with 2-stage closure (36%). The noncleft control group consisted of 63 age
      matched volunteers. MAIN OUTCOME MEASURE(S): Ratings of perceptual voice
      characteristics from blinded voice recordings with Swedish Voice Evaluation
      Approach (SVEA) method. Acoustic voice analysis including pitch and spectral
      measures. RESULTS: Among the patients, the mean values for the 12 evaluated
      variables on a VAS scale (0 = no abnormality, 100 = maximal abnormality) ranged
      between 1 and 22 and the mean for all was 6 mm. Voice variables were similar
      between patients and controls except the total mean of all the perceptual voice
      variables, as well as "vocal fry"-both slightly lower among patients ( P = .018
      and P = .009). There was no difference in any variable between patients treated
      with 1-stage and 2-stage palate closure. No clear relationship was found between
      VPI and dysphonia. CONCLUSION: The voice characteristics among adults treated for
      UCLP in childhood are not different from those of individuals without cleft.

PMID- 29461877
TI  - Active Presurgical Infant Orthopedics for Unilateral Cleft Lip and Palate:
      Intercenter Outcome Comparison of Latham, Modified McNeil, and Nasoalveolar
      Molding.
AB  - OBJECTIVE: To compare dental arch relationship, craniofacial form, and nasolabial
      aesthetic outcomes among cleft centers using distinct methods of presurgical
      infant orthopedics (PSIO). DESIGN: Retrospective cohort study. SETTING: Four
      cleft centers in North America. PATIENTS: One hundred ninety-one children with
      repaired complete unilateral cleft lip and palate (CUCLP). MAIN OUTCOME MEASURES:
      Dental arch relationship was assessed using the GOSLON Yardstick. Craniofacial
      form was assessed by 12 cephalometric measurements. Nasolabial aesthetics were
      assessed using the Asher-McDade system. Assessments were performed between 6 and
      12 years of age. RESULTS: The center that used no PSIO achieved the most
      favorable dental arch relationship and maxillomandibular relationship, with a
      median GOSLON score of 2.3 ( P < .01) and an ANB angle of 5.1 degrees  ( P <
      .05). The proportion of children assigned a GOSLON score of 4 or 5, predictive of
      the need for orthognathic surgery in adolescence, was 16% at the center that used
      no PSIO and no secondary surgery, compared to 76% at the centers that used the
      Latham appliance and early secondary lip and nose surgery ( P < .01). The center
      that used no PSIO and no secondary surgery achieved significantly less favorable
      nasolabial aesthetic outcomes than the centers using Latham appliance or
      nasoalveolar molding (NAM) ( P < .01). CONCLUSIONS: Effects of active PSIO are
      multifaceted and intertwined with use of revision surgery. In our study, centers
      using either the Latham appliance combined with early revision surgery or the NAM
      appliance without revision surgery achieved better nasolabial aesthetic outcomes
      but worse maxillary growth, compared to a center using no PSIO and secondary
      surgery.

PMID- 29461878
TI  - Experience of parents of children with autism on YouTube: are there educationally
      useful videos?
AB  - The aims of this study were to determine the following: first, are there
      educationally useful videos of parents of children with autism sharing their
      experiences? Second, do any of the data related to videos help in identifying
      useful videos? And third, what do posted comments tell us? YouTube was searched
      for videos of parents sharing their experiences. The following parameters were
      collected: title, creator, URL, duration, number of viewers, likes, dislikes,
      comments, days on YouTube, and country. Based on agreed-upon criteria, videos
      were divided independently into educationally useful and non-useful categories. A
      critical thematic analysis of comments was conducted. A total of 180 videos were
      finally identified, of which 106 (59%) provided useful information, scoring 15.3
      +/- 0.7 (mean +/- SD); 74 (41%) were determined to be not educationally useful,
      scoring 8.6 +/- 2.1. The differences in scores were significant (p < 0.001), but
      there were no significant differences between the useful and non-useful groups in
      terms of video parameters. No correlation was found between scores and any of the
      videos' parameters. In conclusion, there are videos that can be used as
      educational resources. The videos' parameters did not differentiate between
      useful and non useful. Useful videos were mostly created by professional
      societies and by parents. The study reflects the emerging role of YouTube in
      sharing experiences.

PMID- 29461879
TI  - Comparing the effectiveness of laser vs. conventional endoforehead lifting.
AB  - The objective of this study was to compare the efficacy and safety of laser
      versus conventional endoforehead lifting. Over a period of 12 years (January 2000
      January 2012), a total of 110 patients with hyperactive muscles over the frontal
      region have been collected for a retrospective study. The SurgiLase 150XJ CO2
      laser system, in conjunction with the flexible FIBERLASE, was used. The endoscope
      was 4 mm in diameter with an angle of 30 degrees . The primary efficacy
      measurement was the assessment of the final outcome for using laser vs.
      conventional methods. Both groups were observed at three weeks, six weeks and six
      months after surgery. The most common complication in early convalescence (three
      weeks) was swelling. This was followed by local paraesthesia, ecchymosis,
      localized hematomas and scar with alopecia. All these problems disappeared
      completely after the 6-month study period. Based on a chi-square analysis, there
      were clinically and statistically significant differences favouring the laser
      endoforehead surgery in the operative time, early and late complications. All
      patients achieved significant improvement after both laser and conventional
      endoforehead surgery in the final outcome. However, the early and late
      complications indicated a greater difference in the laser group.

PMID- 29461880
TI  - Expression Profiles of Six Atherosclerosis-Associated microRNAs That Cluster in
      Patients with Hyperhomocysteinemia: A Clinical Study.
AB  - The aim of this study is to discuss the hypothesis that expression of plasma
      atherosclerosis-associated microRNAs (miRNAs) in hyperhomocysteinemia (Hhcy)
      patients could predict the presence of atherosclerosis from different channels.
      Six plasma miRNAs (miR-145, miR-155, miR-222, miR-133, miR-217, and miR-30)
      selected for our study have been confirmed as critical gene regulators involved
      in atherosclerosis and can be steadily determined in plasma. Expression of the
      above six plasma circulating miRNAs revealed significant upregulation of two
      miRNAs (miR-133 and miR-217) and downregulation of three miRNAs (miR-145, miR
      155, and miR-222). Six candidate miRNAs showed a significant correlation with
      homocysteine (Hcy) or lipid parameters. The results of this study indicated that
      miR-217 was further significantly upregulated in Hhcy + ATH groups than in normal
      control, Hhcy-, and atherosclerosis-alone (ATH) groups and it showed a
      significant negative correlation with Hcy and triglycerides. More specifically,
      miR-217 showed the most specific expression patterns in all patients with
      atherosclerosis (ATH and Hhcy + ATH groups), which may have been a diagnostic
      value for Hhcy complicated with atherosclerosis, and predicted the progress of
      atherosclerosis in Hhcy patients effectively.

PMID- 29461881
TI  - Insights into Macrophage Autophagy in Latent Tuberculosis Infection: Role of Heat
      Shock Protein 16.3.
AB  - Tuberculosis (TB) is a major bacterial infectious disease worldwide that is
      predominantly caused by Mycobacterium tuberculosis (Mtb). The comorbidity of
      multiple drug-resistant TB strains with HIV and diabetes is widespread. In the
      presence of these diseases, host immunity is weakened, allowing the recovery of
      dormant bacilli and leading to recurrent TB infection. As an important component
      of the host innate and adaptive immune responses, macrophage autophagy plays a
      significant role in protecting the host against TB. However, dormant bacilli can
      escape from autophagosomes and/or suppress autophagy, thus surviving within the
      host for an extended period of time, although the underlying mechanism remains
      elusive. Heat shock protein 16.3 (Hsp16.3, HspX, Rv2031c, and Acr) is one of the
      immunodominant proteins expressed during latent TB infection (LTBI). It may help
      maintain the protein stability and long-term viability of Mtb by inhibiting
      macrophage autophagy, resulting in LBTI. In this review, we discuss how dormant
      bacilli escape from autophagosomes, and we focus on the role of Hsp16.3 in
      regulating macrophage autophagy in LTBI so as to provide a firm basis for further
      studies. Hsp16.3 may represent a potential biomarker of LTBI and novel
      pharmacological target for anti-tubercular drugs.

PMID- 29461883
TI  - Structure and Function Relationships in Diseases of the Small Airways.
AB  - It is well known that particulate matter suspended in the earth's atmosphere
      generated by tobacco smoke, automobile exhaust, industrial processes, and forest
      fires has been identified as a major risk factor for chronic lung disease.
      Particulate matter can be divided into large, intermediate, and fine
      particulates. When inhaled, large particulates develop sufficient momentum to
      leave the flowing stream of inhaled air and deposit by impaction in the nose,
      mouth, nasopharynx, larynx, trachea, and central bronchi. Intermediate-sized
      particulates that develop less momentum deposit in the smaller bronchi and larger
      bronchioles, and the finest particulates that develop the least momentum make it
      to the distal gas-exchanging tissue, where gas moves solely by diffusion. On the
      basis of Einstein's classic work on Brownian motion that showed particles
      suspended in a gas diffuse much more slowly than the gas in which they are
      suspended, we postulate that the small airways that accommodate the shift from
      bulk airflow to diffusion become the major site for deposition of fine particles,
      resulting in a host immune response. Much remains to be learned about the
      interaction between the deposition of fine particulates and the host immune and
      tissue responses; the purpose of this review is to examine the hypothesis that
      the smallest conducting airways and proximal gas-exchanging tissue are the
      primary sites for the deposition of the finest particulates inhaled into the
      lungs.

PMID- 29461882
TI  - Genetic Analyses Identified a SALL4 Gene Mutation Associated with Holt-Oram
      Syndrome.
AB  - Holt-Oram syndrome (HOS) is an autosomal dominant disorder, which is
      characterized by deformities of upper limbs and congenital heart defects.
      Alterations of TBX5 gene have been identified to be the leading cause of HOS,
      while some cases could not be explained by TBX5 mutations. In our study, we
      preliminarily diagnosed a newborn baby, who had Tetralogy of Fallot, thumb
      agenesis, facial dysplasia, and right ear canal malformation, as HOS. Chromosome
      microarray analyses showed no pathological deletions or replications of
      chromosome segments; whole exome sequencing screened out six candidate genes that
      were involved in cardiac diseases or syndromes among which SALL4 has been
      reported as HOS related gene. We evaluated the pathogenicity of SALL4 mutant
      sites by series of software. The results indicated that SALL4-M143V may be a
      polymorphism site, and SALL4-R418C could cause disease. HOPE and SWISS PDB viewer
      showed that SALL4-R418C leads to changes in amino acid properties, loss of
      protein hydrogen bond, and functional impact of SALL4 zinc finger domain. These
      results further confirmed the pathogenic significance of SALL4-R418C mutant. When
      genetic analyses coupled with bioinformatic analyses, we identified a SALL4 gene
      rare mutation which might contribute to a newborn with HOS. Although some doubts
      need to be further discussed and explored, our study deepened the understanding
      of phenotype difference among syndromes and role of SALL4 mutations in disease
      occurrence.

PMID- 29461884
TI  - Cournand's and Richards' Post-Nobel Challenge: "Do Anything on the Structure of
      the Lung That Is of Interest for Physiology".
AB  - In their Nobel Lectures of 1956, the two cardiopulmonary physiologists Andre
      Cournand and Dickinson Richards described the future projects that they
      considered important for rounding up their impressive scientific achievements.
      One of them called for work that brought together structure and function of the
      lung in a systematic way. They challenged a young anatomist to undertake this in
      their cardiopulmonary laboratory at Bellevue Hospital. The first steps
      established the need for quantitative information on the structures that form the
      pulmonary gas exchanger as well as the airway tree. This resulted in a new
      approach to lung anatomy: morphometry would provide the quantitative information
      for modeling structure-function relations in the lung, and eventually in the
      entire respiratory system, thus allowing a rational analysis of how structures
      affect or limit functions.

PMID- 29461885
TI  - Physiologic Basis of Mechanical Ventilation.
AB  - The primary purpose of mechanical ventilation is to decrease work of breathing.
      Achieving this goal requires that cycling of the ventilator be carefully aligned
      with the intrinsic rhythm of a patient's respiratory center output. Problems
      arise at the point of ventilator triggering, post-trigger inflation, and
      inspiration-expiration switchover. Careful, iterative adjustments of ventilator
      settings are required to minimize work of breathing. Use of protocols for the
      selection of ventilator settings can lead to complications (including alveolar
      overdistention) and risk of death. Because complications are axiomatic to
      mechanical ventilation, it should be discontinued at the earliest possible time.
      To shorten ventilator time, the critical step is to screen for weanability
      through use of weaning predictor tests. Use of T-tube trials circumvents the
      impossibility of estimating patient work of breathing during pressure support.
      Before extubation, patients should demonstrate the ability to breathe
      successfully in the absence of pressure support and positive end-expiratory
      pressure.

PMID- 29461886
TI  - Cournand and Richards: The Nobel Prize.

PMID- 29461887
TI  - Cor Pulmonale Revisited. From Ferrer and Harvey to the Present.
AB  - The term cor pulmonale has traditionally been used as a synonym for right heart
      failure due to chronic respiratory diseases, although this condition is less
      frequently seen in the modern era because of the use of long-term oxygen therapy
      along with aggressive measures directed at optimizing ventilation and gas
      exchange. The mechanisms by which adaptation or maladaptation of right heart
      structure and function in the broader setting of pulmonary vascular disease,
      either intrinsic to the pulmonary circulation or due to respiratory diseases,
      have garnered considerable interest along with the development of medical and
      surgical treatments for pulmonary hypertension. Thus, the right heart is no
      longer considered an "innocent bystander" in pulmonary hypertension, but rather a
      key component in its pathophysiology. Furthermore, the status of right heart
      function is a major determinant of outcome. Accordingly, the right heart has
      become a potential, appealing target for novel therapies to treat hypertensive
      pulmonary vascular disease.

PMID- 29461888
TI  - Some Unanticipated Consequences of Early Cardiac Catheterization. Insights into
      Pulmonary Pathophysiology.
AB  - One of the most interesting unanticipated findings by Andre Cournand and
      Dickinson Richards in their groundbreaking studies of cardiac catheterization was
      the very low pressure in the normal pulmonary circulation. At the time, in the
      1940s, the significance of this was not appreciated. For example, in their
      speeches at the Nobel Prize ceremony, neither of these laureates referred to the
      low pressure, although they did discuss other features of the pulmonary
      circulation. It was up to the cardiologist, William Dock, to point out that these
      low pressures implied a very uneven distribution of blood flow in the lung, and
      in particular that in the normal upright lung, the blood flow to the apex would
      be extremely small. Dock went on to argue that this low blood flow at the top of
      the lung was responsible for the characteristic apical distribution of adult
      pulmonary tuberculosis. Since that time, it has been recognized that the low
      pressures in the pulmonary circulation have many implications in pulmonary
      pathophysiology. For example, if the vascular pressure is further reduced, such
      as in hemorrhagic shock, gas exchange is seriously affected because of the
      development of a large alveolar dead space. Furthermore, if humans are subjected
      to increased acceleration, such as in a high-performance aircraft, the
      distribution of blood flow becomes extremely abnormal, with much of the lung
      being completely unperfused. There are also diseases where distribution in the
      lung is affected by the uneven distribution of blood flow. These include alpha-1
      antitrypsin deficiency and metastatic calcification of the lung.

PMID- 29461889
TI  - The Evolution of Extracorporeal Membrane Oxygenation for Adult Respiratory
      Failure.
AB  - The use of extracorporeal membrane oxygenation to support patients with cardiac
      and respiratory failure has increased substantially in the last decade. Although
      the evidence base for its use in adults with respiratory failure is growing, many
      questions remain to be answered. Ongoing research is aimed at clarifying the role
      of extracorporeal membrane oxygenation, as well as extracorporeal carbon dioxide
      removal, in various forms of hypoxemic and hypercapnic respiratory failure, and
      at defining the optimal techniques for its use. This, of course, is a moving
      target, as advances in the technology of extracorporeal membrane oxygenation, and
      the potential development of a true artificial lung, continue at a brisk pace.

PMID- 29461890
TI  - Small Airway Disease Syndromes. Piercing the Quiet Zone.
AB  - The role for direct assessment of small airway function in subjects with
      respiratory symptoms but normal airflow by spirometry is discussed. Small airway
      disease syndrome is described in numerous disease states using a
      multidisciplinary approach. Data demonstrate that small airway disease is related
      to presence of respiratory symptoms, exposure to inhaled toxins, presence of
      local and systemic inflammation, and presence of histologic abnormalities within
      the distal lung. Investigation of immunological derangements associated with
      distal airway dysfunction in the setting of normal spirometry may provide insight
      into pathophysiological mechanisms that are present at disease onset. For the
      purposes of this symposium, data were reviewed in selected clinical conditions
      (obesity, environmental inhalational injury, and cigarette smoking) that have
      been recently studied in the Andre Cournand Pulmonary Physiology Laboratory at
      Bellevue Hospital using the forced oscillation technique.

PMID- 29461891
TI  - Pathophysiology of Chronic Systolic Heart Failure. A View from the Periphery.
AB  - Heart failure is a common form of heart disease associated with progressive
      exercise intolerance and high risk of adverse clinical outcome events. The
      pathophysiology of chronic systolic heart failure is fundamentally determined by
      the failure of the circulatory system to deliver oxygen sufficient for metabolic
      needs, and it is best explained by a complex interplay between intrinsic
      abnormalities of ventricular pump function and extracardiac factors that limit
      oxygen use in metabolically active tissues. This brief review highlights the role
      of extracardiac factors (peripheral factors) that may impact exercise capacity in
      patients with chronic systolic heart failure. Reduced metabolic vasodilation
      limits delivery of available cardiac output reserve to skeletal muscle during
      exercise, and it is associated with reduced peak oxygen capacity. Abnormal
      substrate use in skeletal muscle due to reduced skeletal muscle mass, change in
      skeletal muscle fiber type, and mitochondrial dysfunction reduces work efficiency
      and submaximal exercise endurance capacity in patients with systolic heart
      failure. These extracardiac peripheral mechanisms of impaired exercise tolerance
      in chronic heart failure may be targets for novel therapeutic development in this
      patient population.

PMID- 29461893
TI  - Andre Cournand, Bellevue's Cardiopulmonary Laboratory, and Research on Heart
      Failure.
AB  - In 1954-1955, the author served as a research fellow in the cardiopulmonary
      laboratory led by Andre Cournand at Bellevue Hospital in New York. Cournand was a
      pulmonary physiologist and a professor of medicine at Columbia University. In his
      quest to obtain mixed venous blood to calculate pulmonary blood flow, he
      catheterized the right atrium, right ventricle, and pulmonary artery in patients
      and also measured the pressures in these chambers. Cournand and his collaborators
      soon appreciated the enormous potential of cardiac catheterization in deepening
      the understanding of cardiovascular pathophysiology. After a series of
      groundbreaking studies, Cournand and his coworker Dickinson Richards, as well as
      German physician Werner Forssmann, were awarded a Nobel Prize in 1956. Cournand's
      laboratory, his work habits, and his rigorous approach to science are described,
      as well as the stimulation the author received during the author's fellowship. As
      a result, the author went on to extend to the left side of the heart the
      observations that the Cournand group had conducted in the right heart. Also, the
      author continued Cournand's work on heart failure by developing techniques to
      measure ventricular function in patients and to describe the neurohumoral changes
      that occur in human heart failure.

PMID- 29461892
TI  - Human Cognitive Limitations. Broad, Consistent, Clinical Application of
      Physiological Principles Will Require Decision Support.
AB  - Our education system seems to fail to enable clinicians to broadly understand
      core physiological principles. The emphasis on reductionist science, including
      "omics" branches of research, has likely contributed to this decrease in
      understanding. Consequently, clinicians cannot be expected to consistently make
      clinical decisions linked to best physiological evidence. This is a large-scale
      problem with multiple determinants, within an even larger clinical decision
      problem: the failure of clinicians to consistently link their decisions to best
      evidence. Clinicians, like all human decision-makers, suffer from significant
      cognitive limitations. Detailed context-sensitive computer protocols can generate
      personalized medicine instructions that are well matched to individual patient
      needs over time and can partially resolve this problem.

PMID- 29461894
TI  - Rethinking Chronic Obstructive Pulmonary Disease. Chronic Pulmonary Insufficiency
      and Combined Cardiopulmonary Insufficiency.
AB  - Almost 70 years ago, Drs. Baldwin, Cournand, and Richards defined chronic
      pulmonary insufficiency by the presence of respiratory symptoms, radiologic
      evidence of pulmonary emphysema on chest radiography, and physiologic gas
      trapping. A decade later, airflow obstruction on spirometry was added to the
      definition and insufficiency became a disease. Contemporary studies are reviving
      the diagnostic approach described by these early luminaries, with researchers
      finding that symptomatic smokers with preserved spirometry have increased
      exacerbations and that smokers and non-smokers with normal spirometry but
      emphysema on chest computed tomography have increased mortality. Hence, the
      Baldwin-Cournand-Richards concept of disease defined by respiratory symptoms,
      radiologic findings, and physiology-regardless of spirometric criteria-is being
      rediscovered. Baldwin, Cournand, and Richards also stated that "functionally, it
      is obvious that the pulmonary and circulatory apparatus are one unit," and they
      defined combined cardiopulmonary insufficiency as chronic pulmonary insufficiency
      with (left or right) cardiac and pulmonary artery enlargement. They appreciated
      the complexity of these interactions, which include the potential role of gas
      trapping in heart failure with reduced ejection fraction; the impact of emphysema
      on blood flow in heart failure with preserved ejection fraction; multiple
      contributions to cor pulmonale with increased pulmonary artery pressure; and cor
      pulmonale parvus in emphysema; all of which may be amenable to specific
      therapeutic interventions. Given the complexity of heart-lung interactions
      originally identified by Baldwin, Cournand, and Richards and the potentially
      large therapeutic opportunities, large-scale studies are still warranted to find
      specific therapies for subphenotypes of combined cardiopulmonary insufficiency.

PMID- 29461896
TI  - Chronic Obstructive Pulmonary Disease. A Biomarker and a Potential Therapy.
AB  - This article assesses developments in cardiorespiratory medicine since the Nobel
      Prize in Physiology or Medicine was awarded in 1956 for advancements in the study
      of cardiorespiratory disease. In chronic obstructive pulmonary disease, advances
      were accelerated by the discovery of a genetically determined cause for pulmonary
      emphysema in the genetic abnormality alpha-1 antitrypsin deficiency. This causes
      a deficiency of the inhibitor of neutrophil elastase, which results in increased
      degradation of lung elastin and the development of pulmonary emphysema. This
      discovery gave focus to two amino acids that reside only in body elastin,
      desmosine and isodesmosine, which can be measured as biomarkers of elastin
      degradation in body fluids with increased accuracy and sensitivity. Studies of
      this biomarker have shown that augmentation therapy in alpha-1 antitrypsin
      deficiency does decrease lung and body elastic tissue degradation and in the
      RAPID (Randomized, Placebo-controlled Trial of Augmentation Therapy in Alpha-1
      Proteinase Inhibitor Deficiency) Study, over 4 years, showed a preservation of
      lung density by computer tomography correlating with decreases in plasma levels
      of desmosine and isodesmosine. This insight indicates the potential of agents
      that prevent lung elastin degradation. Such an agent is hyaluronan aerosol, which
      is deficient in post mortem lungs with chronic obstructive pulmonary disease and
      has been shown to block elastin degradation, possibly by a barrier function. Thus
      it would appear that hyaluronan could have therapeutic potential in chronic
      obstructive pulmonary disease.

PMID- 29461895
TI  - Scaling Physiologic Function from Cell to Tissue in Asthma, Cancer, and
      Development.
AB  - The formation of an integrated tissue from individual cells depends on the
      properties of the individual cells as well as the interaction of many cells
      acting as a collective. Three fundamental physiological processes govern the
      collective scaling from the individual cell to a working tissue: cell sorting,
      tissue assembly, and collective cellular migration. Mechanistically, cell sorting
      is governed by differential adhesion, whereas tissue assembly is controlled by
      the epithelial-to-mesenchymal transition and its inverse, the mesenchymal-to
      epithelial transition. The mechanism driving collective cellular migration,
      however, is not clear. To fill that gap, here we consider cell jamming and
      unjamming, and their role in collective cellular migration.

PMID- 29461898
TI  - Journal of Health and Social Behavior 2017 Awards for Outstanding Contributions
      to Peer Review.

PMID- 29461897
TI  - RNA/Protein Discordant Expression of Fndc5 in Central Nervous System Is Likely to
      Be Mediated Through microRNAs.
AB  - Fibronectin type III domain-containing 5 protein (Fndc5) is responsible for
      producing a secretory protein termed, "irisin." A modified expression of Fndc5
      has been reported in different tissues during development, differentiation
      processes, as well as in metabolic events such as exercise. One of the important
      issues to be fixed is whether Fndc5 RNA level and protein content are concerted
      and modified hand in hand. Therefore, the aim of this study is to assess Fndc5
      RNA and protein levels in various tissues of mouse and rat with emphasis on
      brain. Biopsies from various parts of neonatal and adult mouse and rat tissues
      were simultaneously assessed for transcript levels of Fndc5 and compared with the
      respective protein levels at the same time. Data indicated, unlike in muscle, no
      concerted fluctuations were observed for Fndc5 RNA and protein, especially in
      brain. Further look at four regions of brain (cerebellum, putamen, hippocampus,
      and cortex) revealed a similar discrepant expression. To hypothesize whether such
      discrepancy is arisen by miRNAs, we selected three main miRNAs, which were
      predicted to target Fndc5 and their expression levels were assessed in central
      nervous system (CNS) of mouse and hippocampus of rat. miRNA levels showed an
      antiparallel correlation with protein level of Fndc5, interpreting a putative
      role in regulating Fndc5 protein content in CNS. This phenomenon may represent
      the importance of governing Fndc5 content in neural cells, which seems to be
      crucial for neural function and differentiation.

PMID- 29461899
TI  - Policy Brief.

PMID- 29461900
TI  - Suppression of LRRC19 promotes cutaneous wound healing in pressure ulcers in
      mice.
AB  - The ischemia-reperfusion (I/R) induced skin lesion has been identified as primary
      cause of pressure ulcer. Better understanding of the mechanism is required for
      new therapy development. Leucine rich repeat containing protein 19 (LRRC19) is a
      recently discovered transmembrane protein containing leucine-rich repeats and
      plays a role in immune response. To investigate the role of LRRC19 in pressure
      ulcers, mouse ulcer model was established with two cycles of I/R. The expression
      of LRRC19 was assessed during injury. siRNA mediated LRRC19 downregulation was
      applied to investigate the disease severity, immune cell infiltration and pro
      inflammatory cytokines production. The primary skin fibroblasts were stimulated
      with IL-1beta to dissect the molecular mechanism. LRRC19 was readily induced in
      I/R induced lesion site in a pattern mimicking the disease progress as measured
      by wound area. Knockdown of LRRC19 by siRNA significantly alleviated the disease
      severity and attenuated immune cell infiltration and pro-inflammatory cytokines
      production. In primary skin fibroblast model, siRNA knockdown of LRRC19
      suppressed IL-1beta mediated NFkappaB activation and its downstream cytokines
      production. LRRC19 was a novel factor for I/R-induced tissue damage by promoting
      NFkappaB dependent pro-inflammatory response. Our results supported that LRRC19
      could be a potential therapeutic target for pressure ulcers.

PMID- 29461901
TI  - Predicting treatment outcome of drug-susceptible tuberculosis patients using
      machine-learning models.
AB  - Tuberculosis (TB) is a deadly contagious disease and a serious global health
      problem. It is curable but due to its lengthy treatment process, a patient is
      likely to leave the treatment incomplete, leading to a more lethal, drug
      resistant form of disease. The World Health Organization (WHO) propagates
      Directly Observed Therapy Short-course (DOTS) as an effective way to stop the
      spread of TB in communities with a high burden. But DOTS also adds a significant
      burden on the financial feasibility of the program. We aim to facilitate TB
      programs by predicting the outcome of the treatment of a particular patient at
      the start of treatment so that their health workers can be utilized in a targeted
      and cost-effective way. The problem was modeled as a classification problem, and
      the outcome of treatment was predicted using state-of-art implementations of 3
      machine learning algorithms. 4213 patients were evaluated, out of which 64.37%
      completed their treatment. Results were evaluated using 4 performance measures;
      accuracy, precision, sensitivity, and specificity. The models offer an
      improvement of more than 12% accuracy over the baseline prediction. Empirical
      results also revealed some insights to improve TB programs. Overall, our proposed
      methodology will may help teams running TB programs manage their human resources
      more effectively, thus saving more lives.

PMID- 29461902
TI  - Excision of nodular basal cell carcinoma involving the lower eyelid tarsal skin
      using a grey line-splitting, posterior lamella-sparing technique.
AB  - PURPOSE: To describe a posterior lamella-sparing technique to resect nodular
      basal cell carcinoma involving the inferior part of the tarsal skin of the lower
      eyelid. SURGICAL TECHNIQUE: Excision of nodular basal cell carcinoma of the
      tarsal skin using a grey-line-splitting technique with preservation of the
      posterior lamella. Specimen was sent for frozen section control. Additional
      excision was performed in caseof irradicality. The defect was closed with a free
      skin graft from the ipsi- or contralateral upper eyelid. RESULTS: We show a case
      series of three patients with lower eyelid basal cell carcinoma and investigated
      radicality on histology, aesthetic outcome and clinical recurrence during a
      follow-up of 18 months. Pre, intra, and postoperative photographs were obtained.
      In all cases radicality was reached. In all patients, the skin graft was viable,
      with no recurrence after 18 months. Excellent aesthetic results were obtained.
      CONCLUSION: Anterior lamellar resection of nodular basal cell carcinomas
      involving the tarsal lower eyelid skin using a grey line lid-splitting technique
      is a simple and one-step technique with good clinical outcome. It may avoid the
      morbidity associated with full thickness eyelid resection and might be useful for
      other, nonmalignant eyelid lesions.

PMID- 29461903
TI  - Habilitation of very preterm infants at a Post Acute Care Inpatient
      Rehabilitation (PACIR) center after neonatal intensive care unit (NICU)
      discharge.
AB  - OBJECTIVE: To investigate whether Post-Acute Care Inpatient Rehabilitation
      (PACIR) admission after NICU stay affects the total length of stay (LOS) of very
      preterm (VPT: <=30 weeks of gestation) infants. METHODS: A retrospective case
      control study of VPT infants d/c'd from the NICU at Maria Fareri Children's
      Hospital (MFCH) to either a PACIR (Blythedale Children's Hospital: BH) for
      convalescent care (cases) or directly home (controls). RESULTS: 35 cases and 70
      controls. Total LOS (MFCH + BH) was longer for cases [196 vs. 97 days]. At the
      time of d/c from MFCH, Special Health Care Needs (SHCN) amongst cases were
      greater than controls, however, became similar at the time of home d/c. The
      majority of cases achieved habilitation goals at the PACIR. CONCLUSIONS: Although
      LOS was longer for patients transferred to a PACIR, habilitation at BH Hospital
      reduced the SHCN at the time of home d/c amongst cases.

PMID- 29461904
TI  - An investigation of the association between seizures, autism symptomology, and
      developmental functioning in young children.
AB  - OBJECTIVE: The aim of the present study was to explore whether a history of
      seizures was associated with autism symptom severity and developmental
      functioning in young children. METHODS: Autism symptom severity and developmental
      functioning were compared between children with and without a history or seizures
      who either had atypical development or met criteria for autism spectrum disorder
      (ASD) based on review of records by a licensed clinical psychologist. RESULTS:
      Parents of children who met criteria for ASD reported lower levels of autism
      symptomology when the child had a history of seizures, while the opposite trend
      was found for children with atypical development. Participants without ASD or
      seizures had greater developmental functioning than the other groups. CONCLUSION:
      The present study emphasizes the need for early identification and diagnosis of
      both ASD and seizure disorders, as timely intervention for these two conditions
      may be related to improved outcomes for young children.

PMID- 29461905
TI  - A case and literature review of orbital microcystic adnexal carcinoma.
AB  - Microcystic adnexal carcinoma (MAC) is a very rare and locally aggressive sweat
      gland tumour. MAC has been well reported presenting as a periocular cutaneous
      lesion, rarely with subsequent direct orbital invasion and only once as a primary
      orbital lesion. Local recurrence is frequent after primary surgical excision and
      the role of adjuvant radiotherapy is ill-defined. We describe a case of orbital
      MAC treated successfully with radiotherapy after incomplete margin clearance post
      exenteration surgery and review the associated literature.

PMID- 29461906
TI  - How does measurement of platelet P-selectin compare with other methods of
      measuring platelet function as a means of determining the effectiveness of
      antiplatelet therapy?
AB  - Measurement of P-selectin on activated platelets as a means of measuring platelet
      function utilizing the technology described here has the advantage of not
      requiring immediate access to specialist equipment and expertise. Blood samples
      are activated, fixed, stored, and transported to a central laboratory for flow
      cytometric analysis. Here we have compared P-selectin with other more traditional
      approaches to measuring platelet function in blood and/or platelet-rich plasma
      (PRP) from patients with acute coronary syndromes on treatment for at least 1
      month with either aspirin and clopidogrel or aspirin with prasugrel. The
      comparators were light transmission aggregometry (LTA), VerifyNow and Multiplate
      aggregometry (for determining the effects of aspirin) and LTA, VerifyNow and
      Multiplate together with the BioCytex VASP phosphorylation assay (for the P2Y12
      antagonists). The P-selectin Aspirin Test revealed substantial inhibition of
      platelet function in all but three of 96 patients receiving aspirin with
      clopidogrel and in none of 51 patients receiving aspirin and prasugrel. The
      results were very similar to those obtained using LTA. There was only one patient
      with high residual platelet aggregation and low P-selectin expression. The same
      patients identified as "non-responders" to aspirin also presented with the
      highest residual platelet activity as measured using the VerifyNow system,
      although not quite as well separated from the other values. With the Multiplate
      test only one of these patients clearly stood out from the others. The results
      obtained using the P-selectin P2Y12 Test in 102 patients taking aspirin and
      clopidogrel were similar to the more traditional approaches in that a wide
      scatter of results was obtained. Generally, high values seen with the P-selectin
      P2Y12 Test were also high with the LTA, VerifyNow, Multiplate, and BioCytex VASP
      P2Y12 Tests. Similarly, low residual platelet function using the P2Y12 test was
      seen irrespective of the testing procedure used. However, there were differences
      in some patients. Prasugrel was always more effective than clopidogrel in
      inhibiting platelet function with none of 56 patients (P-selectin and VerifyNow),
      only 2 of 56 patients (Multiplate) and only 3 of 56 patients (Biocytex VASP)
      demonstrating high on-treatment residual platelet reactivity (HRPR) defined using
      previously published cut-off values. The exception was LTA where there were 11 of
      56 patients with HRPR. It remains to be seen which experimental approach provides
      the most useful information regarding outcomes after adjusting therapies in
      treated patients.

PMID- 29461907
TI  - Personalizing Patients' Advance Directives Decreases the Willingness of Intensive
      Care Unit Residents to Stop Treatment: A Randomized Study.
AB  - BACKGROUND: While following patients' advance directives (ADs) is legally
      binding, French physicians in Intensive Care Unit (ICU) perceive them as
      complicating their decision. Decision making and ICU residents benefit from
      personalizing the dying process. In France, ADs can include personal information.
      OBJECTIVE: Whether personalizing ADs affects ICU residents' decisions and
      perception of the patient. SUBJECTS AND DESIGN: Sixty-six ICU residents assigned
      to three experimental groups and presented with a case file for an ICU patient.
      The files were identical except for the patient's AD, which was manipulated to
      give three conditions: No Personal Information, Sociodemographic Information, and
      Agency Information (ability to plan and act upon the world). MEASUREMENTS:
      Residents evaluated the relevance of the AD, assessed its influence on medical
      decisions, and decided whether to stop treatment, postpone the decision, or
      consult the family. Finally, they evaluated the patient with respect to two
      dimensions of personhood (agency and experience). RESULTS: Residents in all
      conditions considered the AD to be highly relevant and influential. Residents in
      both Information conditions perceived the patient as having more capacities for
      agency and for experience than those in the No Information condition. They were
      also less likely to stop treatment and more likely to postpone their decision.
      Consulting the family was not sensitive to the information condition. CONCLUSION:
      Personalizing ADs of an unknown patient leads ICU residents to be less prone to
      follow them, but does not affect whether or not they decide to consult the
      patient's family. Hence, promoting shared decision making by including the
      incapacitated patients' families in treatment decisions is a major challenge,
      especially in countries such as France, where ADs are legally binding.

PMID- 29461908
TI  - Improving Early Palliative Care with a Scalable, Stepped Peer Navigator and
      Social Work Intervention: A Single-Arm Clinical Trial.
AB  - BACKGROUND: Patients with cancer could benefit from early primary (i.e., basic)
      palliative care. Scalable models of care delivery are needed. OBJECTIVE: Examine
      the feasibility of a stepped peer navigator and social work intervention
      developed to improve palliative care outcomes. DESIGN: Single-arm prospective
      clinical trial. The peer navigator educated patients to advocate for pain and
      symptom management with their healthcare providers, motivated patients to pursue
      advance care planning, and discussed the role of hospice. The social worker saw
      patients with persistent psychosocial distress. SETTING/SUBJECTS: Patients with
      advanced cancer at a VA Medical Center not currently in palliative care or
      hospice whose oncologist would not be surprised if the patient died in the
      subsequent year. MEASUREMENTS: Participation and retention rates, patient
      reported symptoms and quality of life, advance directive documentation, patient
      satisfaction survey, and semistructured interviews. RESULTS: The participation
      rate was 38% (17/45), and 35% (7/17) completed final survey measures. Patients
      had stage IV (81%) and primarily genitourinary (47%) and lung (24%) malignancies.
      Median Eastern Cooperative Oncology Group performance status was 0. Patient
      reported surveys indicated low distress (mean scores: Functional Assessment of
      Cancer Therapy-General, 75.3 [standard deviation {SD} 17.6]; Edmonton Symptom
      Assessment Scale symptom scores ranged from 1.6 to 3.8; Patient Health
      Questionnaire-9, 5.7 [SD 5.2]; and Generalized Anxiety Disorder-7, 2.8 [SD 4.1]).
      Of those who had not completed advance directives at baseline (n = 11, 65%), five
      completed them by the end of study (5/11, 45%). Patients who completed
      satisfaction surveys (n = 7) and interviews (n = 4) provided mixed reviews of the
      intervention. CONCLUSIONS: At a single site, a stepped peer navigator and social
      work palliative care study had several challenges to feasibility, including low
      patient-reported distress and loss to follow-up.

PMID- 29461909
TI  - Moderate influenza vaccine effectiveness against influenza A(H1N1)pdm09 virus and
      low effectiveness against A(H3N2) virus among older adults during 2013-2014
      influenza season in Beijing, China.
AB  - BACKGROUND: Since 2007, trivalent inactivated influenza vaccine has been provided
      free-of-charge to older adults aged >=60 years in Beijing, China, but the data
      regarding influenza vaccine effectiveness (VE) among these people are very
      limited so far. We sought to estimate influenza VE against medically-attended
      laboratory-confirmed influenza illness among older adults during the 2013-2014
      season. METHODS: The influenza-like illness (ILI) patients aged 60 years and
      older who participated in the influenza virological surveillance of Beijing
      during 2013-2014 influenza season were recruited in this study. A test-negative
      design was employed to estimate influenza VE among older adults by using logistic
      regression models. VE was estimated using logistic regression, adjusted for sex,
      age, interval (days) between illness onset and specimen collection, and week of
      illness onset. RESULTS: Between 1 November, 2013 and 30 April, 2014, a total of
      487 elderly ILI patients were enrolled in the study, including 133 influenza
      positive cases (of whom 6.8% were vaccinated) and 354 influenza-negative controls
      (of whom 10.2% were vaccinated). Among 133 influenza-positive cases, 51 tested
      positive for A(H1N1)pdm09 virus, 22 positive for A(H3N2) virus, 52 tested
      positive for B/Yamagata-lineage virus, 2 positive for B/Victoria-lineage virus, 1
      positive for both A(H1N1)pdm09 and A(H3N2) viruses, and 5 tested positive for
      viruses of unknown subtype or lineage. The adjusted overall VE was estimated as
      32% (95% CI:-48-69), with 59% (95% CI: -79-90) against A(H1N1)pdm09, 22% (95% CI:
      -253-83) against A(H3N2) and -20% (95% CI: -239-58) against B/Yamagata-lineage
      viruses. CONCLUSIONS: These results suggested a modest protective effect of the
      2013-2014 influenza vaccine among older adults in Beijing which was not
      statistically significant, with higher VE against the A(H1N1)pdm09 viruses
      compared to A(H3N2) and B viruses.

PMID- 29461911
TI  - Small cell lung cancer transformation from EGFR-mutated lung adenocarcinoma: A
      case report and literatures review.
AB  - Epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have
      markedly improved the response of non-small cell lung cancer (NSCLC) with EGFR
      mutant patients. However, these patients inevitably come cross acquired
      resistance to EGFR-TKIs. The transformation of lung adenocarcinoma to small cell
      lung cancer (SCLC) following treatment with EGFR-TKIs is rare, which leads to
      resistance to EGFR-TKIs. The present case concerns a case of a 38-year-old man
      presenting with cough and dyspnea. Radical resection was performed and confirmed
      an EGFR exon 21 L858R lung adenocarcinoma. However, the patient suffered pleural
      metastasis after successful treatment with surgery and adjuvant treatment. So,
      erlotinib was administered with 18 months. Because of enlarged pleural nodule,
      repeat biopsy identified an SCLC and chemotherapy was started. However, despite
      the brief success of chemotherapy, our patient suffered brain metastasis. Our
      case emaphsizes both the profile of transformation from NSCLC to SCLC and the
      importance of repeat biopsy dealing with drug resistance. We also summarize the
      clinical characteristics, mechanisms, predictors of SCLC transformation,
      treatment after transformation and other types of transformation to SCLC.

PMID- 29461912
TI  - Practice and attitudes towards immunization among Lebanese obstetricians and
      gynecologists.
AB  - We designed our study to evaluate the knowledge and immunization practices among
      Lebanese obstetricians and gynecologists (OBGYN) for women of different age
      groups. Anonymous questionnaires were used to assess the knowledge and
      immunization practices among OBGYN. The survey was conducted at the annual
      meeting of the Lebanese Society of Obstetrics and Gynecology on November 13-15,
      2014. Data collected included demographics, type of practice, academic background
      and familiarity with vaccine guidelines. Descriptive statistical methods were
      used to evaluate the responses. The response rate was 54.8% (114/208). Only 62.3%
      (71/114) recommend vaccination(s) to pregnant women with only 25.9% of those who
      recommend the Tdap vaccine for pregnant women giving it during the recommended
      third trimester. In addition, 52.6% are unaware of the CDC/ACIP immunization
      schedule for women in general. However, 83.0% (93/112) of respondents are willing
      to integrate vaccination in their practice. Our study highlights several gaps in
      the knowledge of Lebanese OBGYN regarding vaccination in addition to practices
      that are not in full accordance with common guidelines. Measures should be taken
      to spread proper awareness of the proper guidelines among Lebanese practitioners.

PMID- 29461910
TI  - Measuring and interpreting platelet-leukocyte aggregates.
AB  - Platelets, besides their specialised role in haemostasis and atherothrombosis,
      actively modulate innate and adaptive immune responses with crucial roles in
      immune surveillance, inflammation and host defence during infection. An important
      prerequisite for platelet-mediated changes of immune functions involves direct
      engagement with different types of leukocytes. Indeed, increased platelet
      leukocyte aggregates (PLAs) within the circulation and/or locally at the site of
      inflammation represent markers of many thrombo-inflammatory diseases, such as
      cardiovascular diseases, acute lung injury, renal and cerebral inflammation.
      Therefore, measurement of PLAs could provide an attractive and easily accessible
      prognostic and/or diagnostic tool for many diseases. To measure PLAs in different
      (patho-)physiological settings in human and animal models flow cytometric and
      microscopic approaches have been applied. These techniques represent
      complementary tools to study different aspects relating to the involvement of
      leukocyte subtypes and molecules, as well as location of PLAs within tissues,
      dynamics of their interactions and/or dynamic changes in leukocyte and platelet
      behaviour. This review summarises various approaches to measure and interpret
      PLAs and discusses potential experimental factors influencing platelet binding to
      leukocytes. Furthermore, we summarise insights gained from studies regarding the
      underlying mechanism of platelet-leukocyte interactions and discuss implications
      of these interactions in health and disease.

PMID- 29461913
TI  - Immunogenicity and safety of the first indigenously developed Indian tetravalent
      influenza vaccine (split virion) in healthy adults >= 18 years of age: A
      randomized, multicenter, phase II / III clinical trial.
AB  - This phase II / III clinical trial was conducted to evaluate the immunogenicity
      and safety of the Tetravalent Influenza vaccine (Split virion) I.P. (TetIV)
      developed indigenously in the country for the first time by M/s Cadila Healthcare
      Limited, India containing two influenza A and two influenza B strains, one of
      each, Yamagata (B/Phuket) and Victoria (B/Brisbane) lineage and also compare it
      to that of an licensed seasonal Trivalent Influenza vaccine (TriIV) of Sanofi
      Pasteur India Private Limited, containing the two influenza A and only the
      Yamagata lineage (B/Phuket) strain. Three hundred and fifty subjects of either
      sex, aged more than 18 years of age, were randomized in a 1:1 ratio to receive
      either the TetIV or TriIV. Immunogenicity assessments (antibody against A/H1N1,
      A/H3N2, B/Phuket and B/Brisbane) were done by Haemagglutination Inhibition assay
      at baseline and 21 d after vaccination. Solicited (local and systemic) and
      unsolicited adverse events were recorded for up to 42 d following vaccination.
      The TetIV was found to fulfill the criteria set by the European and the US
      regulatory authorities and WHO guidance on the requirements of clinical data for
      licensure of seasonal inactivated influenza vaccines. The seroconversion rates
      with TetIV were 93.5% for A/H1N1, 90.0% for A/H3N2, 70.0% for B/Phuket and 82.9%
      for B/Brisbane strain. There was no significant difference in the seroconversion
      and seroprotection rates at day 21 for A/H1N1, A/H3N2 and B/Phuket in the two
      groups while the TetIV was superior to the TrivIV for the seroconversion and the
      seroprotection rate for the B/Brisbane strain (Victoria lineage). Both the
      vaccines were well tolerated by all the study participants; addition of the
      fourth strain in the TetIV did not compromise the safety as compared to TriIV.
      The most common systemic adverse event reported in both the groups was headache
      followed by fever.

PMID- 29461914
TI  - Comparison of Open Versus Laparoscopic Versus Hand-Assisted Laparoscopic
      Nephroureterectomy: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: A systematic analysis of the evidence regarding oncological,
      perioperative and postoperative outcomes of open nephroureterectomy (ONU),
      laparoscopic nephroureterectomy (LNU), and hand-assisted laparoscopic
      nephroureterectomy (HALNU) was designed. METHODS: The summarized data were
      abstracted from 52 original research articles representing 19,195 patients.
      PubMed/Medline, Scopus, Google Scholar, EMBASE, and the Cochrane Library were
      reviewed in March 2017, following PRISMA framework. A total of 52 publications
      were selected for inclusion. The primary outcomes were 2- and 5-year cancer
      specific survival (CSS) rate, overall survival (OS) rate, and recurrence-free
      survival (RFS) rate. The secondary outcomes were operative time, lengths of
      hospitalization period, estimated blood loss, transfusions, major Clavien
      complication rate, metastasis rate, bladder recurrence rate, and positive
      surgical margin. RESULTS: On comparing LNU versus ONU and HALNU versus ONU, no
      significant differences between the 5-year CSS rate (P = .25, P = .39), OS rate
      (P = .06, P = .46), and RFS rate (P = .85, P = .73) were found. On comparing LNU
      versus ONU and HALNU versus ONU during a 2-year follow-up period, the following
      were found: CSS rate (P = .61, P = .04) and OS rate (P = .33, P = .19). There
      were no significant differences between the LNU versus ONU and HALNU versus ONU
      rates, regarding bladder recurrence (P = .12, P = .85) and metastasis rate (P =
      .07, P = .27). Significant higher operative time (P = .01, P = .0004), lower
      length of hospitalization period (P < .001, P < .001), and estimated blood loss
      (P = .0004, P < .001) were found in comparison to that of LNU versus ONU and
      HALNU versus ONU. CONCLUSION: Both LNU and HALNU had comparable oncological and
      better perioperative and postoperative outcomes, when compared with ONU.

PMID- 29461915
TI  - A novel method for automated assessment of megakaryocyte differentiation and
      proplatelet formation.
AB  - Transfusion of platelet concentrates represents an important treatment for
      various bleeding complications. However, the short half-life and frequent
      contaminations with bacteria restrict the availability of platelet concentrates
      and raise a clear demand for platelets generated ex vivo. Therefore, in vitro
      platelet generation from megakaryocytes represents an important research topic. A
      vital step for this process represents accurate analysis of thrombopoiesis and
      proplatelet formation, which is usually conducted manually. We aimed to develop a
      novel method for automated classification and analysis of proplatelet-forming
      megakaryocytes in vitro. After fluorescent labelling of surface and nucleus, MKs
      were automatically categorized and analysed with a novel pipeline of the open
      source software CellProfiler. Our new workflow is able to detect and quantify
      four subtypes of megakaryocytes undergoing thrombopoiesis: proplatelet-forming,
      spreading, pseudopodia-forming and terminally differentiated, anucleated
      megakaryocytes. Furthermore, we were able to characterize the inhibitory effect
      of dasatinib on thrombopoiesis in more detail. Our new workflow enabled rapid,
      unbiased, quantitative and qualitative in-depth analysis of proplatelet formation
      based on morphological characteristics. Clinicians and basic researchers alike
      will benefit from this novel technique that allows reliable and unbiased
      quantification of proplatelet formation. It thereby provides a valuable tool for
      the development of methods to generate platelets ex vivo and to detect effects of
      drugs on megakaryocyte differentiation.

PMID- 29461916
TI  - Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy:
      American Society of Clinical Oncology and Infectious Diseases Society of America
      Clinical Practice Guideline Update.
AB  - Purpose To provide an updated joint ASCO/Infectious Diseases Society of American
      (IDSA) guideline on outpatient management of fever and neutropenia in patients
      with cancer. Methods ASCO and IDSA convened an Update Expert Panel and conducted
      a systematic review of relevant studies. The guideline recommendations were based
      on the review of evidence by the Expert Panel. Results Six new or updated meta
      analyses and six new primary studies were added to the updated systematic review.
      Recommendation Clinical judgment is recommended when determining which patients
      are candidates for outpatient management, using clinical criteria or a validated
      tool such as the Multinational Association of Support Care in Cancer risk index.
      In addition, psychosocial and logistic considerations are outlined within the
      guideline. The panel continued to endorse consensus recommendations from the
      previous version of this guideline that patients with febrile neutropenia receive
      initial doses of empirical antibacterial therapy within 1 hour of triage and be
      monitored for >= 4 hours before discharge. An oral fluoroquinolone plus
      amoxicillin/clavulanate (or clindamycin, if penicillin allergic) is recommended
      as empirical outpatient therapy, unless fluoroquinolone prophylaxis was used
      before fever developed. Patients who do not defervesce after 2 to 3 days of an
      initial, empirical, broad-spectrum antibiotic regimen should be re-evaluated and
      considered as candidates for inpatient treatment. Additional information is
      available at www.asco.org/supportive-care-guidelines and
      www.asco.org/guidelineswiki .

PMID- 29461917
TI  - Enhancing the Value of Dental Biomaterials Research: "Reducing the Noise".

PMID- 29461918
TI  - Feasibility of a Video-Based Advance Care Planning Website to Facilitate Group
      Visits among Diverse Adults from a Safety-Net Health System.
AB  - BACKGROUND: Primary care providers in safety-net settings often do not have time
      to discuss advance care planning (ACP). Group visits (GV) may be an efficient
      means to provide ACP education. OBJECTIVES: To assess the feasibility and impact
      of a video-based website to facilitate GVs to engage diverse adults in ACP.
      DESIGN: Feasibility pilot among patients who were >=55 years of age from two
      primary care clinics in a Northern California safety-net setting. Participants
      attended two 90-minute GVs and viewed the five steps of the movie version of the
      PREPARE website ( www.prepareforyourcare.org ) concerning surrogates, values, and
      discussing wishes in video format. Two clinician facilitators were available to
      encourage participation. MEASUREMENTS: We assessed pre-to-post ACP knowledge,
      whether participants designated a surrogate or completed an advance directive
      (AD), and acceptability of GVs and PREPARE materials. RESULTS: We conducted two
      GVs with 22 participants. Mean age was 64 years (+/-7), 55% were women, 73%
      nonwhite, and 55% had limited literacy. Knowledge improved about surrogate
      designation (46% correct pre vs. 85% post, p = 0.01) and discussing decisions
      with others (59% vs. 90%, p = 0.01). Surrogate designation increased (48% vs.
      85%, p = 0.01) and there was a trend toward AD completion (9% vs. 24%, p = 0.21).
      Participants rated the GVs and PREPARE materials a mean of 8 (+/-3.1) on a 10
      point acceptability scale. CONCLUSIONS: Using the PREPARE movie to facilitate ACP
      GVs for diverse adults in safety net, primary care settings is feasible and shows
      potential for increasing ACP engagement.

PMID- 29461920
TI  - A Randomized Controlled Trial for Veterans with PTSD and Substance Use Disorder:
      Creating Change versus Seeking Safety.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) and substance use disorder (SUD)
      co-occur in military veterans and other populations. OBJECTIVE: To conduct a
      randomized controlled trial to compare a new past-focused treatment (Creating
      Change; CC), to a well-established, evidence-based present-focused treatment for
      PTSD/SUD (Seeking Safety; SS), on symptoms of both disorders. CC guides patients
      to process the past through exploration of PTSD/SUD life themes and memories
      whereas SS focuses on coping skills in the present. METHODS: Fifty-two male and
      female veterans with current PTSD/SUD were randomized (n = 26 per treatment) and
      assessed at baseline, end-of-treatment and 3-month follow-up. They received 17
      individual one-hour sessions. RESULTS: Intent-to-treat analyses indicated that
      both conditions improved over time, with no difference between conditions, on
      PTSD, alcohol use, and drug use (our primary outcomes) as well as mental health
      symptoms, quality of life, self-efficacy, and SUD cognitions. Effect sizes were
      medium except for alcohol use, which was large. Change over time reflected
      improvement from baseline to end-of-treatment, with gains sustained at follow-up,
      although alcohol use showed continued improvement from end-of-treatment to follow
      up. Both treatments evidenced a strong safety profile; and attendance, alliance,
      and treatment satisfaction were also very strong. Conclusions/importance: CC has
      promise as a PTSD/SUD therapy with strong public health relevance and the
      potential to fill important gaps in the field. We used minimal exclusionary
      criteria to obtain a real-world sample, which was severe-predominantly substance
      dependent with chronic PTSD and additional psychiatric diagnoses. Future research
      is warranted, especially on nonveteran samples and treatment mechanisms of
      action.

PMID- 29461919
TI  - Persistence of immune response to an adjuvanted varicella-zoster virus subunit
      vaccine for up to year nine in older adults.
AB  - BACKGROUND: In adults aged >=60 years, two doses of the herpes zoster subunit
      vaccine (HZ/su; 50 ug varicella-zoster virus glycoprotein E [gE] and AS01B
      Adjuvant System) elicited humoral and cell-mediated immune responses persisting
      for at least six years. We assessed immunogenicity nine years post-initial
      vaccination. METHODS: This open extension study (NCT02735915) followed 70
      participants who received two HZ/su doses in the initial trial (NCT00434577).
      Blood samples to assess the cellular (intracellular cytokine staining) and
      humoral (ELISA) immunity were taken at year nine post-initial vaccination.
      RESULTS: Participants' mean age at dose 1 was 72.3 years. The fold increases over
      pre-vaccination in the mean frequency of gE-specific CD4+ T-cells expressing >=2
      activation markers plateaued from year four post-dose 1 until year nine. Anti-gE
      antibody geometric mean concentrations plateaued and remained above pre
      vaccination levels from year four onwards. Immunogenicity at year nine was
      similar across age strata (60-69, >=70 years) and confirmed statistical
      prediction model results using data for up to year six. Further modeling using
      all data up to year nine predicted immune responses would remain above the pre
      vaccination level up to year 15. CONCLUSION: In adults aged >=60 years, HZ/su
      induced immunogenicity remained above pre-vaccination levels for at least nine
      years post-initial vaccination. SUMMARY: After vaccination with HZ/su, both cell
      mediated and humoral immunity remained above pre-vaccination levels up to year 9
      regardless of age group. Immune responses are predicted to remain above baseline
      up to 15 years post initial vaccination.

PMID- 29461921
TI  - Porous orbital implant after enucleation in retinoblastoma patients: indications
      and complications.
AB  - This study aims to identify risk factors associated with complications in
      retinoblastoma patients following primary and secondary enucleations with porous
      implant placement. A retrospective case-control study was performed between 2010
      and 2015. Data pertaining to subjects' demographics, medical history, clinical,
      and pathological findings, implant characteristics and complications were
      collected. The analysis included 103 eyes of 101 patients age 27.8 +/- 21.9
      months undergoing enucleation for retinoblastoma. Postoperatively, 19/103 (18%)
      eyes developed exposure, extrusion, or hematoma requiring subsequent surgery.
      Exposure was the most common postoperative complication (12/19, 63%). Age at
      enucleation 24 months or younger, Hispanic ethnicity, female gender, and
      intravenous chemotherapy prior to enucleation were associated with increased odds
      of implant complications. In contrast, patients who were given intravitreal
      melphalan (IM), subtenons carboplatin (SC), or external beam radiation therapy
      (EBRT) did not demonstrate an increased risk of complications. In this cohort of
      retinoblastoma patients undergoing primary or secondary enucleation with porous
      implants, implant exposure was the most common postoperative complication. Our
      findings suggest that female gender, Hispanic ethnicity, age at enucleation 24
      months or younger, and intravenous chemotherapy prior to enucleation may increase
      the risk of complications.

PMID- 29461922
TI  - A fishy eyelid injury.
AB  - A 9-year-old girl was reviewed by a tertiary ophthalmology service after being
      hit in her right upper eyelid by a fish whilst swimming. Initial wound
      exploration demonstrated fish scales in the wound. She was first treated
      conservatively with washout of the 5-mm wound and was discharged with oral
      ciprofloxacin. Five days later, the patient re-presented with a worsened ptosis
      due to periorbital swelling. Ultrasound of the upper lid demonstrated a foreign
      body in the upper lid. The patient was taken to theatre and, with the assistance
      of intraoperative ultrasound, the jaws of a needle fish were removed from the
      upper lid. The case highlights the importance of ultrasound and its
      intraoperative utility in cases of trauma and a suspicion of retained foreign
      bodies as well as the potential danger of fish injuries off the West Australian
      coast.

PMID- 29461923
TI  - Disquisition on the interaction of ibuprofen-Zn(II) complex with calf thymus DNA
      by spectroscopic techniques and the use of Hoechst 33258 and Methylene blue dyes
      as spectral probes.
AB  - The interaction between ibuprofen-Zn(II) complex and calf thymus DNA in
      physiological buffer (pH 7.4) was studied with the use of Hoechst 33258 and
      methylene blue dyes as spectral probes by multi-spectroscopic techniques, and
      viscosity measurements. It was found that ibuprofen-Zn(II) complex molecules
      could bind with DNA via groove binding mode as evidenced by: i- DNA binding
      constant (Kb = (1.00 +/- 0.2) * 104 M-1) from Spectrophotometric studies of the
      interaction of ibuprofen-Zn(II) complex with DNA is comparable to groove binding
      drugs. ii- Absorption Spectra of Competitive interaction of ibuprofen-Zn(II)
      complex and Hoechst 33258 with DNA exhibited the reverse process, The results
      suggested that interaction of the ibuprofen-Zn(II) complex with calf thymus DNA,
      is similar to Hoechst 33258 interaction with calf thymus DNA (This was verified
      by the following fluorescence study). iii- Competitive fluorimetric studies with
      Hoechst 33258 have shown that ibuprofen-Zn(II) complex exhibit the ability of
      this complex to displace with DNA-bounded Hoechst 33258, indicating that it binds
      to DNA in strong competition with Hoechst 33258 for the groove binding. iv- There
      is no significantly change in the fluorescence intensity of the MB-DNA system
      upon adding the ibuprofen-Zn(II) complex, indicate that MB molecules are not
      released from the DNA helix after addition of the ibuprofen-Zn(II) complex and
      are indicative of a non-intercalative mode of binding. v- Small changes in DNA
      viscosity in the presence of ibuprofen-Zn(II) complex, indicating weak link to
      DNA, which is consistent with DNA groove binding. As well as, induced CD spectral
      changes, and the docking results revealed that groove mechanism is followed by
      ibuprofen-Zn(II) complex to bind with DNA.

PMID- 29461924
TI  - Controlling alpha for mixed effects models for repeated measures.
AB  - Mixed Effects Models for Repeated Measures (MMRM) is often used in clinical
      trials with longitudinal data. However, there has not been an in-depth
      examination available on how investigators can implement interim analysis while
      also controlling the overall alpha for clinical trials under an MMRM analysis
      framework. Statistical independence among measurements, which is often assumed in
      group sequential testing (GST), is not valid under an MMRM framework due to the
      correlations induced by longitudinal within-subject measurements. Therefore,
      methods associated with GST derived under independence need to be adjusted
      accordingly. While these correlations can be estimated from the study data,
      regulatory agencies may not accept results based on these estimated correlations
      since there is no guarantee that the overall alpha is strongly controlled. In
      this article, we propose a new AC-Hybrid-approach for controlling the overall
      alpha. The AC-Hybrid-approach has two key attributes. First, we apply the MMRM
      analysis framework on all available data at every analysis timepoint. Second, we
      use complete-case information fractions to derive the group sequential stopping
      boundaries. We prove that the overall alpha is controlled regardless of the
      correlations among within-subject measurements. We also show the impact of this
      approach on the alpha and the power through examples.

PMID- 29461925
TI  - Negative Affect Intensity and Hostility in Individuals With Alcohol Use Disorder
      With or Without Posttraumatic Stress Disorder.
AB  - OBJECTIVE: Negative affect intensity and hostility have both been implicated in
      alcohol use disorders (AUD) and posttraumatic stress disorder (PTSD) when they
      occur separately, but neither have been compared or explored among those with
      comorbid AUD and PTSD. This study is a secondary analysis designed to compare
      levels of negative affect intensity and hostility among those with AUD to those
      with comorbid AUD and PTSD. METHODS: Participants (n = 113) were recruited from
      the placebo-controlled groups of two distinct 12-week clinical trials
      (NCT00342563 and NCT00744055). The Short Affect Intensity Scale and Buss-Durkee
      Hostility Inventory were administered at weeks 0, 4, 8, and 12 to all study
      participants to assess negative affect intensity and hostility levels,
      respectively. RESULTS: Individuals with comorbid AUD and PTSD showed
      significantly higher levels of negative affect intensity and hostility than
      individuals with AUD only. These levels remained relatively stable over the
      course of the study in spite of all study participants showing clinically
      significant improvements in AUD severity and PTSD symptomatology (for those with
      dual diagnosis). CONCLUSIONS: Our results indicate that individuals with comorbid
      AUD and PTSD have higher levels of negative affect and higher levels of hostility
      compared to individuals with AUD alone. In addition, these heightened levels of
      negative affect intensity and hostility appear to function somewhat independently
      of diagnosis severity and symptomatology improvement. To our knowledge, this is
      the first study to compare negative affect intensity and hostility levels between
      individuals with AUD alone and those with comorbid AUD and PTSD.

PMID- 29461926
TI  - The relationship between social status and the components of agency.
AB  - Building on the two fundamental dimensions of social judgment distinguishing
      communion from agency, the purpose of the present work was to show that the
      strength of the relationship between social status and agency depends on specific
      components at issue: assertiveness, competence, and effort. Four experimental
      studies were conducted using two complementary paradigms. In Studies 1 and 2, we
      manipulated social status, and participants had to rate the target on competence,
      assertiveness, and effort. In Studies 3 and 4, we reversed the design. Results
      consistently showed that social status was primarily related to assertiveness,
      somewhat related to competence, and only slightly related to effort. The present
      research provides a better understanding of how the dimensions of social judgment
      are used to explain differences in social status.

PMID- 29461927
TI  - Event-Based Conformity Versus Regression to the Mean: A Comment on Kim and Hommel
      (2015).

PMID- 29461928
TI  - Comparison of Clinical Isolates of Aeromonas from Singapore and Malaysia with
      Regard to Molecular Identification, Virulence, and Antimicrobial Profiles.
AB  - OBJECTIVE: The objective of this study was to examine the species distribution,
      genetic relatedness, virulence gene profiles, antimicrobial sensitivities, and
      resistance gene distribution of clinical Aeromonas strains from Singapore and
      Malaysia. METHODS: A total of 210 Aeromonas clinical isolates were investigated:
      116 from Singapore General Hospital and 94 archived clinical isolates from
      University of Malaya Medical Center, Malaysia. The isolates were genetically
      identified based on the gcat gene screening and the partial sequences of the rpoD
      housekeeping gene. Genetic relatedness, distribution of 15 virulence genes and 4
      beta-lactamase resistance genes, and susceptibility patterns to 11 antimicrobial
      agents were compared. RESULTS: Of the 210 Aeromonas isolates, A. dhakensis-94
      (45%) was the dominant species in Singapore and Malaysia. Species composition was
      similar and enterobacterial repetitive intergenic consensus-PCR did not show
      genetic relatedness between strains from the two countries. Of the 15 virulence
      genes, A. dhakensis and A. hydrophila harbored the most compared with other
      species. Different combinations of 9 virulence genes (exu, fla, lip, eno, alt,
      dam, hlyA, aexU, and ascV) were present in A. dhakensis, A. hydrophila, and A.
      veronii from both the countries. Distribution of virulence genes was species and
      anatomic site related. Majority (>80%) of the strains were susceptible to all
      antimicrobial agents tested, except amoxicillin and cephalothin. A. dhakensis
      strains from Malaysia significantly harbored the cphA gene compared with A.
      dhakensis from Singapore. Multidrug resistance was mostly detected in strains
      from peritoneal fluids of dialysis patients. CONCLUSION: This study revealed A.
      dhakensis as the dominant species isolated in both geographic regions, and that
      it carried a high number of virulence genes. It also highlights the geographic
      related differences of virulence gene distribution and antimicrobial resistance
      profiles of clinical Aeromonas strains from Singapore and Malaysia.

PMID- 29461929
TI  - Impact of the Antibiotic Stewardship Program on Prevention and Control of
      Surgical Site Infection during Peri-Operative Clean Surgery.
AB  - BACKGROUND: Surgical site infections (SSIs) are the leading cause of hospital
      acquired infections and are associated with substantial healthcare costs, with
      increased morbidity and mortality. To investigate the effects of the antibiotic
      stewardship program on prevention and control of SSI during clean surgery, we
      investigated this situation in our institution. PATIENTS AND METHODS: We
      performed a quasi-experimental study to compare the effect before and after the
      antibiotic stewardship program intervention. During the pre-intervention stage
      (January 1, 2010 through December 31, 2011), comprehensive surveillance was
      performed to determine the SSI baseline data. In the second stage (January 1,
      2012 through December 31, 2016), an infectious diseases physician and an
      infection control practitioner identified the surgical patients daily and
      followed up on the duration of antimicrobial prophylaxis. RESULTS: From January
      1, 2010 to December 31, 2016, 41,426 patients underwent clean surgeries in a
      grade III, class A hospital. The rate of prophylactic antibiotic use in the
      41,426 clean surgeries was reduced from 82.9% to 28.0% after the interventions.
      The rate of antibiotic agents administered within 120 minutes of the first
      incision increased from 20.8% to 85.1%. The rate at which prophylactic
      antimicrobial agents were discontinued in the first 24 hours after surgery
      increased from 22.1% to 60.4%. Appropriate antibiotic selection increased from
      37.0% to 93.6%. Prophylactic antibiotic re-dosing increased from 3.8% to 64.8%.
      The SSI rate decreased from 0.7% to 0.5% (p < 0.05). The pathogen detection rate
      increased from 16.7% up to 41.8% after intervention. The intensity of antibiotic
      consumption reduced from 74.9 defined daily doses (DDDs) per 100 bed-days to 34.2
      DDDs per 100 bed-days after the interventions. CONCLUSION: Long-term and
      continuous antibiotic stewardship programs have important effects on the
      prevention and control of SSI during clean surgery.

PMID- 29461930
TI  - The Role of Cannabinoid Receptor 1 in the Immunopathology of Respiratory
      Syncytial Virus.
AB  - Endocannabinoid system plays an important role in pathophysiologic processes such
      as immune functions and impacts on disease severity. Our previous study showed
      that cannabinoid receptor 2 (CB2) affects clinical course of respiratory
      syncytial virus (RSV) infection. In this study, we investigated the role of
      cannabinoid receptor 1 (CB1) in RSV immunopathology and its therapeutic potential
      in mice model. To study the role of CB1 receptors in the immunopathology of RSV,
      CB1 was blocked daily with AM281 as a selective antagonist in Balb/c mice and
      were infected by intranasal inoculation of RSV-A2 24 h following the first dose
      of antagonist administration. The potential pharmacological therapeutic effects
      of cannabinoid receptor activation during RSV infection were studied using JZL184
      as a selective indirect agonist, 24 h after infection. Mice were sacrificed on
      day 5 after infection and experimental analyses were performed to study the CB1
      receptor expression, airway immune cell influx, cytokine/chemokine secretion,
      lung histopathology, and viral load. RSV infection of airways significantly
      induced the expression of CB1 receptors in lung cells of mice. Blockade of CB1
      receptors using AM281 enhanced immune cell influx and cytokine/chemokine
      production, and aggravated lung pathology. Activation of cannabinoid receptors
      using JZL184 decreased immune cell influx and cytokine/chemokine production, and
      alleviated lung pathology. This study and our previous finding indicated that
      endocannabinoid signaling regulates the inflammatory response to RSV infection,
      and is a potential therapeutic candidate for alleviation of RSV-associated
      immunopathology.

PMID- 29461931
TI  - Use of Cold Fluids in Postcardiac Arrest Therapeutic Hypothermia: A Safety
      Analysis.
AB  - Therapeutic hypothermia (TH) has been part of the standard care of
      postresuscitation patients for more than a decade. Multiple cooling methods are
      available, including the administration of cold intravenous (IV) fluids. Although
      this method is widely used, the safety of administration of large volumes of cold
      IV fluids has not been clearly demonstrated in the literature, and recent
      evidence points to potential deleterious effects associated with administration
      of large IV fluid volumes. We conducted a retrospective cohort study among
      patients who have been treated with TH after cardiac arrest between November 2011
      and November 2013 at a tertiary care hospital in Sherbrooke, Quebec, Canada. The
      primary outcome was the effect of IV fluid quantity on the 28-day survival rate.
      We reviewed 29 cases, with a total 28-day surviving rate of 51.7%. After
      adjusting for confounding variables, 28-day surviving rate was not significantly
      associated with the amount of fluids administrated (odds ratio = 1.034;
      confidence interval 95% [0.741-1.464]; p = 0.85). The amount of fluids did not
      influence the variation of the pulmonary component of the sequential organ
      failure assessment score between days 1 and 3 (rho = -0.2, p = 0.34). Despite a
      small sample of patients, cold IV fluids in TH appear safe in the postcardiac
      arrest population. These findings should be reproduced in a larger, prospective
      study.

PMID- 29461932
TI  - Clinical Outcomes From a 10-Week Follow-Up Psychoeducational Program for Dual
      Diagnosis.
AB  - BACKGROUND: Dual diagnosis covers a broad spectrum of mental health and substance
      misuse conditions occurring concurrently (NICE, 2016 ). Its manifestation is
      complex and, as such, the disorder is recognized as influencing adherence to
      prescribed medication and service engagement and has a worse prognosis than
      substance use and mental health conditions occurring independently. AIMS: To
      determine the effectiveness of psychoeducational group therapy in a sample of
      dual diagnosis patients. METHODS: Patients who met the Diagnostic and Statistical
      Manual of Mental Disorders-IV Axis 1 criteria for serious mental illness and
      current substance misuse were approached to take part in a psychoeducational
      program. Those who consented were assessed at baseline and end point using
      measures of psychiatric symptomology, psychological well-being, and substance use
      patterns with the following scales: the Brief Psychiatric Rating Scale, the
      Hospital Anxiety and Depression Rating Scale, the Maudsley Addiction Profile
      Scale, and the Warwick-Edinburgh Mental Wellbeing Scale. RESULTS: Fifty-one
      patients completed the program, while 29 dropped out after initial assessment.
      Between baseline and follow-up, there was a decline in the number of participants
      using alcohol, cannabis, cocaine, amphetamine, illicit benzodiazepines and
      methadone. However, the number of participants using heroin remained constant.
      The mean amount of substances used was not reduced over the study period except
      in the case of alcohol. Overall improvements in symptomology and psychological
      well-being were observed. DISCUSSION: Mental health services should focus on
      integrated approaches via multimodal treatment interventions that encapsulate
      harm reduction and educational initiatives: Despite the modest sample, the
      findings have emphasized the importance of a broad range of treatment approaches
      delivered within a unitary delivery system.

PMID- 29461933
TI  - Identifying Priorities for Aging Policies in Two Portuguese Communities.
AB  - The aging population has an impact on health, social, and economic issues in
      regard to individuals, communities, and organizations. The challenge for local
      policies in response to aging is to create sufficient resources to meet the
      population's needs, wishes, and rights as people age. Active aging constitutes
      one of the guiding perspectives on policies. Taking into account the local
      governance perspective, the Model for Aging Local Policies Analysis (MALPA) was
      created in order to convert the active aging paradigm into a practical approach,
      as a technique to evaluate and analyze local aging policies. In this research,
      the MALPA instrument was applied in two Portuguese communities (Coruche and
      Oeiras). The objective was to identify the intervention priorities of aging
      policies in both communities, determining whether the instrument can facilitate
      the development of proposals for the improvement of local aging policies. It was
      possible to evaluate the communities and programs, identifying the least
      appropriate policy actions regarding the intervention priorities. The results
      allowed us to identify 10 priorities about collaborative governance, involvement
      of the elderly in the policy-making process, lifelong learning, economic
      hardship, policies for all ages, isolated vulnerable and fragile groups,
      intergenerational contacts, safety in all policies, labor opportunities, and
      conditions and transport network improvement.

PMID- 29461934
TI  - Risk and Protective Factors for Self-Harm in a Population-Based Sample of
      Transgender Youth.
AB  - This study sought to identify factors distinguishing transgender/gender non
      conforming (GNC) adolescents across three groups: no self-harm, non-suicidal self
      injury (NSSI) only, and NSSI and suicide attempt (NSSI + SA). Data were from the
      2016 Minnesota Student Survey. The final analytic sample included 1,635
      transgender/GNC students in grades 9 and 11. Logistic regression analyses
      determined factors that best distinguished transgender/GNC students who reported
      self-harm (NSSI only or NSSI + SA) from those who reported no self-harm, and
      transgender/GNC adolescents who reported NSSI + SA from those who reported NSSI
      only. Final models were developed over 3 stages of analysis that tested
      associations of variables within risk factor, protective factor, and health-risk
      behavior domains to self-harm. Over half (51.6%) of transgender/GNC adolescents
      reported past-year self-harm behavior. Factors that consistently distinguished
      transgender/GNC youth who reported self-harm from those who reported no self-harm
      included reports of a mental health problem, depression, running away from home,
      and substance use (alcohol or marijuana use). Factors that distinguished the NSSI
      + SA group from the NSSI only group were reports of a mental health problem,
      physical or sexual abuse, relationship violence, bullying victimization, less
      parent connectedness, lower grades, lower levels of perceived school safety, and
      running away from home. Clinicians and school personnel need to be prepared to
      address risk factors and enhance protective factors that may reduce the
      likelihood this population of vulnerable youth will engage in NSSI and/or attempt
      suicide.

PMID- 29461935
TI  - Menstrual Cycle Effects on Mental Health Outcomes: A Meta-Analysis.
AB  - The premenstrual phase of cycle has long been associated with a constellation of
      health symptoms for women. However, there has been no recent quantitative review
      of severe mental health outcomes as a function of the menstrual cycle. We examine
      cycle influences on completed suicides, suicide attempts, suicidal ideation, and
      psychiatric admissions, and contrast these with non-suicide deaths. We conducted
      a meta-analysis of 32 papers, with an N of 3,791. We find 26% greater risk of
      suicide deaths, 17% greater risk of suicide attempts, and 20% greater risk of
      psychiatric admissions at menstruation. We also observe 13% greater risk of
      psychiatric admissions during the premenstrual phase. Suicidal ideation was
      unrelated to the stage of menstrual cycle. Available evidence finds serious and
      consequential mental health outcomes in the menstrual and premenstrual phases.

PMID- 29461936
TI  - Quantification of trunk and android lean mass using dual energy x-ray
      absorptiometry compared to magnetic resonance imaging after spinal cord injury.
AB  - OBJECTIVE: To determine whether dual energy x-ray absorptiometry (DXA) compared
      to magnetic resonance imaging (MRI) may accurately quantify trunk lean mass (LM)
      after chronic spinal cord injury (SCI) and to investigate the relationships
      between trunk LM, visceral adiposity, trunk fat mass and basal metabolic rate
      (BMR). DESIGN: Cross-sectional design and correlational analysis. SETTING:
      Research setting in a medical center. PARTICIPANTS: Twenty-two men with motor
      complete paraplegia (n = 14; T4-T11) and tetraplegia (n = 8; C5-C7) were
      recruited as part of a clinical trial. INTERVENTIONS: Not applicable. OUTCOME
      MEASURES: Trunk and android LM were measured using DXA. The volume of six trunk
      muscle groups were then measured using MRI to quantify trunk LM-MRI. Subcutaneous
      and visceral adipose tissue (VAT) cross-sectional areas were also measured using
      MRI. After overnight fast, BMR was evaluated using indirect calorimetry. RESULTS:
      Trunk LM-DXA (24 +/- 3.3 kg) and android LM-DXA (3.6 +/- 0.7 kg) overestimated (P
      < 0.0001) trunk LM-MRI (1.7 +/- 0.5 kg). Trunk LM-MRI = 0.088* log (trunk LM-DXA)
      0.415; r2=0.29, SEE= 0.44 kg, P = 0.007. Trunk LM-MRI = 1.53* android LM-DXA +
      0.126; r2=0.26, SEE= 0.21 kg, P = 0.018. Percentage trunk LM-MRI was inversely
      related to VAT (r=-0.79, P < 0.0001) and trunk fat mass (r=-0.83, P < 0.001).
      Only trunk LM-DXA was related to BMR (r = 0.61, P = 0.002). Persons with
      tetraplegia have 13% smaller trunk muscle cross-sectional areas (P = 0.036)
      compared to those with paraplegia. CONCLUSIONS: Trunk LM-DXA and android LM-DXA
      overestimated trunk LM-MRI. Percentage trunk LM-MRI, but not LM-DXA, was
      inversely related to trunk central adiposity. The findings highlight the
      importance of exercising trunk LM to attenuate cardio-metabolic disorders after
      SCI.

PMID- 29461937
TI  - Singular stochastic control model for algae growth management in dam downstream.
AB  - A stochastic control model for finding an ecologically sound, fit-for-purpose dam
      operation policy to suppress bloom of attached algae in its downstream is
      presented. A singular exactly solvable and a more realistic regular-singular
      cases are analysed in terms of a Hamilton-Jacobi-Bellman equation. Regularity and
      consistency of the value function are analysed and its classical verification
      theorem is established. Practical implications of the mathematical analysis
      results are discussed focusing on parameter dependence of the optimal controls.
      An asymptotic analysis with a numerical computation reveals solution behaviour of
      the Hamilton-Jacobi-Bellman equation near the origin, namely at the early stage
      of algae growth.

PMID- 29461938
TI  - Use of a self-reported psychosocial distress screening tool as a predictor of
      need for psychosocial intervention in a general medical setting.
AB  - This study describes the development of a self-reported psychosocial distress
      screening tool for a general medical population and criteria to predict the need
      for psychosocial intervention. The objectives were to develop criteria to
      determine which patients need in-person screening and establish criteria
      identifying patients who are more likely to require psychosocial interventions.
      The outcomes have bearing on reducing initial psychosocial screening workload for
      medical social workers in high volume medical settings. Furthermore, a criterion
      for scoring the self-reported tool can predict which patients will need further
      social work intervention. The results suggest criteria are a score on the adapted
      Distress Thermometer of five or greater, at least two negative emotions, and a
      lack of health insurance. The optimal criterion identified 36% (446/1228) of
      patients in need of in-person screening with the remaining 64% (782/1228)
      screened low risk through the tool, representing a significant workload
      reduction.

PMID- 29461940
TI  - Evaluation of an avatar-based training program to promote suicide prevention
      awareness in a college setting.
AB  - OBJECTIVE: Training programs exist that prepare college students, faculty, and
      staff to identify and support students potentially at risk for suicide. Kognito
      is an online program that trains users through simulated interactions with
      virtual humans. This study evaluated Kognito's effectiveness in preparing users
      to intervene with at-risk students. PARTICIPANTS: Training was completed by 2,727
      university students, faculty, and staff from April, 2014 through September, 2015.
      METHODS: Voluntary and mandatory participants at a land-grant university
      completed Kognito modules designed for higher education, along with pre- and post
      assessments. RESULTS: All modules produced significant gains in reported
      Preparedness, Likelihood, and Self-Efficacy in intervening with troubled
      students. Despite initial disparities in reported abilities, after training
      participants reported being similarly capable of assisting at-risk students,
      including LGBTQ and veteran students. CONCLUSIONS: Kognito training appears to be
      effective, on a large scale, in educating users to act in a facilitative role for
      at-risk college students.

PMID- 29461939
TI  - Antibacterial Properties of Four Novel Hit Compounds from a Methicillin-Resistant
      Staphylococcus aureus-Caenorhabditis elegans High-Throughput Screen.
AB  - There is an urgent need for the discovery of effective new antimicrobial agents
      to combat the rise of bacterial drug resistance. High-throughput screening (HTS)
      in whole-animal infection models is a powerful tool for identifying compounds
      that show antibacterial activity and low host toxicity. In this report, we
      characterize the activities of four novel antistaphylococcal compounds identified
      from an HTS campaign conducted using Caenorhabditis elegans nematodes infected
      with methicillin-resistant Staphylococcus aureus (MRSA). The hit compounds
      included an N-hydroxy indole-1, a substituted melamine derivative-2, N
      substituted indolic alkyl isothiocyanate-3, and p-difluoromethylsulfide analog-4
      of the well-known protonophore carbonyl cyanide m-chlorophenyl hydrazone. Minimal
      inhibitory concentrations (MICs) of the four compounds ranged from 2 to 8 MUg/ml
      against MRSA-MW2 and Enterococcus faecium and all were bacteriostatic. The
      compounds were mostly inactive against Gram-negative pathogens, with only 1 and 4
      showing slight activity (MIC = 32 MUg/ml) against Acinetobacter baumanii.
      Compounds 2 and 3 (but not 1 or 4) were found to perturb MRSA membranes. In
      phagocytosis assays, compounds 1, 2, and 4 inhibited the growth of internalized
      MRSA in macrophages, whereas compound 3 showed a remarkable ability to clear
      intracellular MRSA at its MIC (p < 0.001). None of the compounds showed hemolytic
      activity at concentrations below 64 MUg/ml (p = 0.0021). Compounds 1, 2, and 4
      (but not 3) showed synergistic activity against MRSA with ciprofloxacin, while
      compound 3 synergized with erythromycin, gentamicin, streptomycin, and
      vancomycin. In conclusion, we describe four new antistaphylococcal compounds that
      warrant further study as novel antibacterial agents against Gram-positive
      organisms.

PMID- 29461942
TI  - ATP Synthase, a Target for Dementia and Aging?
AB  - Advancing age is the biggest risk factor for development for the major life
      threatening diseases in industrialized nations accounting for >90% of deaths.
      Alzheimer's dementia (AD) is among the most devastating. Currently approved
      therapies fail to slow progression of the disease, providing only modest
      improvements in memory. Recently reported work describes mechanistic studies of
      J147, a promising therapeutic molecule previously shown to rescue the severe
      cognitive deficits exhibited by aged, transgenic AD mice. Apparently, J147
      targets the mitochondrial alpha-F1-ATP synthase (ATP5A). Modest inhibition of the
      ATP synthase modulates intracellular calcium to activate AMP-activated protein
      kinase to inhibit mammalian target of rapamycin, a known mechanism of lifespan
      extension from worms to mammals.

PMID- 29461943
TI  - Is Low-Dose Radiation Exposure a Risk Factor for Atherosclerotic Disease?
AB  - Nontargeted late effects of radiation include an increased risk of cardiovascular
      disease, although this is still debatable in the context of low-dose radiation.
      Tinea capitis patients treated in childhood with X rays to induce scalp epilation
      received a low dose of radiation to their carotids. To better clarify this issue,
      we evaluated carotid atherosclerosis in a cohort of such patients treated in 1950
      1963 in Portugal. A group of 454 individuals randomly chosen from previously
      observed Portuguese tinea capitis patients and a control group mainly composed of
      their spouses (n = 280) were enrolled. Cardiovascular risk factors such as waist
      circumference, body mass index, blood pressure and tobacco consumption, as well
      as biochemical measurements were obtained. Ultrasound imaging of carotid arteries
      for intima media thickness and stenosis evaluation were performed according to a
      standardized protocol. In comparison to the control group, the irradiated cohort
      members were significantly older, more frequently never smokers, hypertensive,
      and presented higher glycated hemoglobin and alkaline phosphatase levels. In
      addition, the irradiated cohort showed a higher frequency of carotid stenosis
      >=30% than the nonirradiated group (13.9% vs. 10.7%), although this was not
      significant ( P = 0.20). Stenosis was >=50% in 2.9% of the irradiated group and
      0.4% of the nonirradiated group ( P = 0.02). Likewise, the frequency of intima
      media thickness >=1 mm was significantly higher in the irradiated group (16.8%
      vs. 10.7%; P = 0.02). Multivariate analysis, including other cardiovascular risk
      factors, showed that exposure to low-dose radiation increased the risk of carotid
      stenosis by >=50% [odds ratio (OR) = 8.85; P = 0.04] and intima media thickness
      by >=1 mm (OR = 1.82; P = 0.02). These findings confirm that low-dose exposure is
      a risk factor of carotid atherosclerotic disease.

PMID- 29461944
TI  - Cervical Internal Carotid Artery Occlusion versus Pseudo-Occlusion: Can CT
      Angiography Help Distinguish These in the Acute Stroke Setting?

PMID- 29461945
TI  - Case 255.

PMID- 29461947
TI  - Detection of Clinically Significant Prostate Cancer by Using Abbreviated
      Biparametric Prostate MR Imaging.

PMID- 29461948
TI  - Case 251: Nontraumatic Drug-associated Rhabdomyolysis of Head and Neck Muscles.
AB  - History A 21-year-old man with a history of abuse of multiple drugs and mild
      cognitive impairment who initially underwent treatment for excited delirium
      developed respiratory arrest shortly after admission and was successfully
      resuscitated. Unenhanced computed tomography (CT) of the head and neck and
      contrast material-enhanced CT of the chest, abdomen, pelvis, and complete spine
      were performed shortly after the initial treatment. Head and neck magnetic
      resonance (MR) imaging was performed 24 hours after admission. No other
      abnormalities were noted. There were no fractures, and there was no vascular
      injury in the head and neck region. The patient had no external neck injuries,
      congestion, or petechiae suggesting neck compression. He had no history of
      chronic or recurrent pain or skin rash. Urine testing was positive for cocaine,
      cannabis, and methamphetamine. Serum creatine kinase level was initially high (31
      117 U/L [520 MUkat/L]; normal, 1000 U/L [16.7 MUkat/L]). Corrected calcium level
      was 2.22 mmol/L, and ionized calcium level was 1.09 mmol/L (lower end of the
      normal range). There was no acute renal failure at the initial phase, but serum
      creatinine levels reached 180 umol/L 24 hours after admission, and creatine
      kinase peaked at 61 000 U/L [1019 MUkat/L]. Urine was initially red, but the
      patient was not tested for myoglobinuria.

PMID- 29461950
TI  - Immediate Allergic Reactions to Gadolinium-based Contrast Agents.

PMID- 29461952
TI  - The Power of Publishing.

PMID- 29461951
TI  - Football and the Brain: Does Career Duration Provide Protective Effects?

PMID- 29461953
TI  - Can Machine Learning Be Used to Generate a Model to Improve Management of High
      Risk Breast Lesions?

PMID- 29461954
TI  - Is CT Colonography Better Tolerated than Flexible Sigmoidoscopy for Colorectal
      Cancer Screening?

PMID- 29461955
TI  - Deep Learning of Radiology Reports for Pulmonary Embolus: Is a Computer Reading
      My Report?

PMID- 29461956
TI  - Imaging Pediatric Appendicitis: Time to Put the Discussion to Bed?

PMID- 29461949
TI  - Quantitative Elastography Methods in Liver Disease: Current Evidence and Future
      Directions.
AB  - Chronic liver diseases often result in the development of liver fibrosis and
      ultimately, cirrhosis. Treatment strategies and prognosis differ greatly
      depending on the severity of liver fibrosis, thus liver fibrosis staging is
      clinically relevant. Traditionally, liver biopsy has been the method of choice
      for fibrosis evaluation. Because of liver biopsy limitations, noninvasive methods
      have become a key research interest in the field. Elastography enables the
      noninvasive measurement of tissue mechanical properties through observation of
      shear-wave propagation in the tissue of interest. Increasing fibrosis stage is
      associated with increased liver stiffness, providing a discriminatory feature
      that can be exploited by elastographic methods. Ultrasonographic (US) and
      magnetic resonance (MR) imaging elastographic methods are commercially available,
      each with their respective strengths and limitations. Here, the authors review
      the technical basis, acquisition techniques, and results and limitations of US-
      and MR-based elastography techniques. Diagnostic performance in the most common
      etiologies of chronic liver disease will be presented. Reliability,
      reproducibility, failure rate, and emerging advances will be discussed. (c) RSNA,
      2018 Online supplemental material is available for this article.

PMID- 29461957
TI  - Disease activity and dropout in young persons with juvenile idiopathic arthritis
      in transition of care: a longitudinal observational study.
AB  - OBJECTIVES: Reaching a certain age, juvenile idiopathic arthritis (JIA) patients
      in paediatric care are transferred to adult care. An increased disease activity
      after transfer and increased dropout has been suggested, however, evidence is
      scarce. Our aim is to determine whether the process of transition is associated
      with increased disease-activity and dropout, and to identify associated factors.
      METHODS: During a 3-year prospective transition cohort study, paediatric patients
      (14-17yrs) were transferred to adult care. Paediatric (10-13yrs) and adult JIA
      patients (18-27yrs) were used as control groups. Demographic and disease-related
      items were obtained yearly. Non-parametric tests were used to compare differences
      between the groups and mixed models to evaluate disease activity over time,
      measured by JADAS27 and DAS28. Dropout was defined as not attending the clinic
      for 2 consecutive visits. RESULTS: Groups did not differ regarding baseline
      variables of subtype, gender, uveitis, ANA-, RF- or HLA B27-positivity and
      current or past DMARD use. Median disease activity was not different between
      groups during follow-up. Transfer was not associated with disease activity.
      Dropout rate was 12%, and was significantly higher in patients under transition
      (22%) compared with paediatric (3%) and adult care (10%). Patients who dropped
      out had significantly lower disease activity at baseline and were using less MTX,
      but did not differ regarding subtype, ANA, RF and HLA-B27. CONCLUSIONS: The
      process of transition in JIA is not associated with an increase in disease
      activity, however, this period carries a risk for drop out especially in patients
      with low disease activity.

PMID- 29461958
TI  - Gout in Duke Federico of Montefeltro (1422-1482): a new pearl of the Italian
      Renaissance.
AB  - The article examines the truthfulness of historical accounts claiming that
      Renaissance Duke Federico of Montefeltro (1422-1482) suffered from gout. By
      direct paleopathological assessment of the skeletal remains and by the
      philological investigation of historical and documental sources, primarily a 1461
      handwritten letter by the Duke himself to his personal physician, a description
      of the symptoms and Renaissance therapy is offered and a final diagnosis of gout
      is formulated. The Duke's handwritten letter offers a rare testimony of ancient
      clinical self-diagnostics and Renaissance living-experience of gout. Moreover,
      the article also shows how an alliance between historical, documental and
      paleopathological methods can greatly increase the precision of retrospective
      diagnoses, thus helping to shed clearer light onto the antiquity and evolution of
      diseases.

PMID- 29461959
TI  - One year in review 2017: spondyloarthritis.
AB  - The term spondyloarthritis (SpA) represents a condition characterised by a broad
      spectrum of clinical manifestations, laboratory abnormalities and imaging
      features; in particular, SpA is an inflammatory condition in which both
      peripheral and axial joints might be affected. The majority of people with this
      disease have either psoriatic arthritis or axial spondyloarthritis, which
      includes ankylosing spondylitis. Less common subgroups are enteropathic SpA,
      which is associated with inflammatory bowel diseases (Crohn's disease and
      ulcerative colitis), reactive arthritis, which can occur in people following
      gastrointestinal or genitourinary infections and undifferentiated SpA, that does
      not meet the diagnostic criteria of the other subgroups at onset, but that may
      evolve to do so later. Very interestingly, much of the emerging data show how
      SpA, during its course, tends to associate with the development of some
      comorbidities; in particular, with cardiovascular diseases, diabetes mellitus,
      osteoporosis and depressive disorders. Healthcare professionals in non-specialist
      settings do not always recognise the signs and symptoms of SpA, particularly
      spinal symptoms, which may be mistakenly attributed to other causes of low back
      pain, thus leading to significant delays in diagnosis and treatment of the
      disease itself and of its related comorbidities, with consequent disease
      progression and disability, compromising the health-related quality of life of
      patients. In this paper we reviewed the literature of the past year (Medline
      search of articles published from 1st March 2016 to 28th February 2017) with the
      aim of approaching the spectrum of SpA from some different points of view, to try
      to give the reader an insight into this clinically challenging group of rheumatic
      pathologies.

PMID- 29461960
TI  - An overview of pathways encoding nociception.

PMID- 29461961
TI  - Long-term continuation of methotrexate therapy in giant cell arteritis patients
      in clinical practice.

PMID- 29461962
TI  - Loop-Mediated Isothermal Amplification test for the diagnosis of pertussis in
      Japan.

PMID- 29461963
TI  - Response to the letter by Dr. Nawa, Loop-Mediated isothermal amplification test
      for the diagnosis of pertussis in Japan.

PMID- 29461964
TI  - Feature-Based Representation Improves Color Decomposition and Nuclear Detection
      Using a Convolutional Neural Network.
AB  - Detection of nuclei is an important step in phenotypic profiling of 1) histology
      sections imaged in bright field; and 2) colony formation of the 3-D cell culture
      models that are imaged using confocal microscopy. It is shown that feature-based
      representation of the original image improves color decomposition (CD) and
      subsequent nuclear detection using convolutional neural networks independent of
      the imaging modality. The feature-based representation utilizes the Laplacian of
      Gaussian (LoG) filter, which accentuates blob-shape objects. Moreover, in the
      case of samples imaged in bright field, the LoG response also provides the
      necessary initial statistics for CD using nonnegative matrix factorization.
      Several permutations of input data representations and network architectures are
      evaluated to show that by coupling improved CD and the LoG response of this
      representation, detection of nuclei is advanced. In particular, the frequencies
      of detection of nuclei with the vesicular or necrotic phenotypes, or poor
      staining, are improved. The overall system has been evaluated against manually
      annotated images, and the F-scores for alternative representations and
      architectures are reported.

PMID- 29461965
TI  - Post-Ventricular Premature Contraction Phase Correction Improves the Predictive
      Value of Average T-Wave Alternans in Ambulatory ECG Recordings.
AB  - OBJECTIVE: We proposed and evaluated a method for correcting possible phase
      shifts provoked by the presence of ventricular premature contractions (VPCs) for
      a better assessment of T-wave alternans (TWA).  Methods: First, we synthesized
      ECG signals with artificial TWA in the presence of different noise sources. Then,
      we assessed the prognostic value for sudden cardiac death (SCD) of the long-term
      average of TWA amplitude (the index of average alternans, ) in ambulatory ECG
      signals from congestive heart failure (CHF) and evaluated whether it is sensitive
      to the presence of VPCs. RESULTS: The inclusion of the phase correction after VPC
      in the processing always improved estimation accuracy of the under different
      noisy conditions and regardless of the number of the VPCs included in the
      sequence. It also presented a positive impact on the prognostic value of with
      increased hazard ratios (from 17% to 29%, depending of the scenario) in
      comparison to the noninclusion of this step. CONCLUSION: The proposed methodology
      for estimation, which corrects for the possible phase reversal on TWA after the
      presence of VPCs, represents a robust TWA estimation approach with a significant
      impact on the prognostic value of for SCD stratification in CHF patients.
      SIGNIFICANCE: An accurate TWA estimation has a potential direct clinical impact
      on noninvasive SCD stratification, allowing better identification of patients at
      higher risk and helping clinicians in adopting the most appropriate therapeutic
      strategy.

PMID- 29461966
TI  - Anxiety and perceived psychological stress play an important role in the immune
      response after exercise.
AB  - There are common pathways by which psychological stress and exercise stress alter
      immunity. However, it remains unknown whether psychological stress plays a role
      in the in vivo immune response to exercise. We examined the relationship between
      anxiety and perceived psychological stress reported before exercise and in vivo
      immunity after exercise using skin sensitisation with Diphenylcyclopropenone
      (DPCP). In a randomised design, sixty four, thoroughly familiarised, males
      completed widely used psychological instruments to assess state-anxiety and
      perceived psychological stress before exercise, and ran either 30 minutes at 60%
      (30MI) or 80% (30HI) V . O2peak, 120 minutes at 60% (120MI) V . O2peak or rested
      (CON) before DPCP sensitisation. Cutaneous recall to DPCP was measured as the
      dermal thickening response to a low-dose series DPCP challenge 4-weeks after
      sensitisation. After accounting for exercise (R2 = 0.20; P < 0.01), multiple
      regression showed that pre-exercise state-anxiety (STAI-S; DeltaR2 = 0.19; P <
      0.01) and perceived psychological stress (DeltaR2 = 0.13; P < 0.05) were
      moderately associated with the DPCP response after exercise. The STAI-S scores
      before exercise were considered low-to-moderate in these familiarised individuals
      (median split; mean STAI-S of low 25 and moderate 34). Further examination showed
      that the DPCP response after exercise (30MI, 30HI or 120MI) was 62% lower in
      those reporting low vs. moderate state-anxiety before exercise (mean difference
      in dermal thickening: -2.6 mm; 95% CI: -0.8 to -4.4 mm; P < 0.01). As such, the
      results indicate a beneficial effect of moderate (vs. low) state-anxiety and
      perceived psychological stress on in vivo immunity after exercise. Moreover,
      correlations were of comparable strength for the relationship between
      physiological stress (heart rate training impulse) and the summed dermal response
      to DPCP (r = -0.37; 95% CI: -0.05 to -0.62; P = 0.01), and state-anxiety and the
      summed dermal response to DPCP (r = 0.39; 95% CI: 0.08 to 0.63; P < 0.01). In
      conclusion, state-anxiety and perceived psychological stress levels before
      exercise play animportant role in determining the strength of the in vivo immune
      response after exercise. These findings indicate a similar strength relationship
      for the level of state-anxiety prior to exercise and the level of physiological
      stress during exercise with the in vivo immune response after exercise. Future
      research is required to investigate exercise-immune responses in athletes,
      military personnel and others in physically demanding occupations experiencing
      higher levels of psychological stress than those reported in this study e.g.
      related to important competition, military operations and major life events.
      Nevertheless, the present findings support the recommendation that exercise
      scientists should account for anxiety and psychological stress when examining the
      immune response to exercise.

PMID- 29461967
TI  - Effects of lifelong training on senescence and mobilization of T lymphocytes in
      response to acute exercise.
AB  - BACKGROUND/PURPOSE: Ageing has profound impact on the immune system, mainly on T
      cells. However, it has been suggested that chronic exercise may delay
      immunosenescence. Master athletes represent an interesting sub-demographic group
      to test this theory since they maintain a high training frequency and load
      throughout life. The purpose of this study was to evaluate the effects of
      lifelong training on the senescence and mobilization of T lymphocytes in response
      to acute exercise. MATERIAL AND METHODS: Nineteen athletes who regularly
      participated in training and competitions for more than 20 years throughout their
      lives and a control group of 10 healthy individuals participated in this study.
      All subjects performed a progressive test to exhaustion on a cycle ergometer.
      Blood samples were obtained before (Pre), 10 min after the test (Post) and 1 h
      after the test (1h). Phenotypic study of peripheral blood T-cells was performed
      by flow cytometry. Genes of interest expression was done on T-cells purified by
      cell sorting. RESULTS: Master athletes had a lower percentage of senescent naive,
      central memory and effector memory CD8+ T-cells and senescent naive and effector
      memory CD4+ T-cells. Age had a positive effect on SLEC CD8+ T-cells and a
      negative effect on naive CD8+ T-cells. VO2max positively correlated with the
      proportion of naive CD4+ T-cells and negatively correlated with the percentage of
      total lymphocytes. No differences were founded for CD4+ and CD8+ T-cells and
      their subsets between master athletes and the control group at all times of
      measurement. No differences were observed in the CD45RA expressing effector
      memory cells (EMRA) for the various study conditions. The mRNA expression of the
      CCR7 gene for naive CD8+ T-cells and the Fas-L gene for effector-terminal CD8+ T
      cells was not different between masters and controls and did not change in
      response to the maximal protocol test. CONCLUSION: In conclusion, maintaining
      high levels of aerobic fitness during the natural course of aging may help
      prevent the accumulation of senescent T-cells.

PMID- 29461968
TI  - The Role of Exercise and Hyperlipidaemia in Breast Cancer Progression.
AB  - Exercise reduces the risk of breast cancer development and improves survival in
      breast cancer patients. However, the underlying mechanisms of this protective
      effect remain to be fully elucidated. It is unclear whether exercise can
      attenuate or modify the pro-tumour effects of obesity and related conditions,
      such as hyperlipidaemia. This review summarises how hyperlipidaemia and exercise
      contribute to or reduce breast cancer risk and progression, respectively, and
      highlights the possible mechanisms behind each. In particular, the effects of
      exercise and hyperlipidaemia on the immune microenvironment of tumours is
      analysed. The potential value of commonly investigated circulating factors as
      exercise-modulated, prognostic biomarkers is also discussed. We propose that
      exercise may alleviate some of the pro-tumorigenic effects of hyperlipidaemia
      through the reduction of blood lipid levels and modulation of cytokine release to
      induce beneficial changes in the tumour microenvironment.

PMID- 29461969
TI  - Toll like receptor expression induced by exercise in obesity and metabolic
      syndrome: A systematic review.
AB  - BACKGROUND: Obesity and metabolic syndrome are disorders that correlate with the
      activation of pro-inflammatory pathways and cytokine production, to which Toll
      like receptors (TLR) contribute. Exercise may act as an anti-inflammatory
      modulator, but there is no consensus about the role of the TLR in this tuning.
      The present styudy aims to systematically review the current evidence on exercise
      induced TLR regulation in animals and humans suffering from obesity and metabolic
      syndrome. METHODS: Pubmed and Scopus databases were searched for publications
      from 1990 to September 2015. Search terms included: "Toll like Receptor", "TLR",
      "exercise", "obesity", "diabetes", and "metabolic syndrome". Elegibility criteria
      comprised: randomized control trials, cross-sectional and cohort studies; human
      or animal models with metabolic syndrome; any type of exercise; TLR expression
      measurement in any tissue by a clearly reported technique. The quality of
      selected studies was assessed using a modified version of the Downs and Black
      Quality Assessment Checklist. Data of study design; population; exercise type,
      timing and training elements; measurement technique, tissue analyzed and main
      outcome were extracted and categorized to facilitate data synthesis. RESULTS: 17
      studies were included, of which 11 publications obtained a high, 5 a moderate and
      1 a low score for quality assessment. A total of 8 human studies were analyzed: 6
      studies used endurance continuous or interval training protocols, 1 study
      resistance training and the remaining study was performed following a marathon
      race. Blood cells were analyzed in seven studies, of which four studies sampled
      peripheral blood mononuclear cells (PBMC), three analyzed whole blood and one
      study sampled skeletal muscle. Nine animal studies were included: 8 used
      endurance training and 1 acute aerobic exercise. A variety of tissues samples
      were explored such as PBMC, skeletal muscle, adipose, vascular and nervous
      tissue. Globally, the animal studies showed a marked tendency towards a down
      regulation of TLR2 and 4 expression accompagnied with, a reduced activation of
      nuclear factorkappaB (NF-kappaB) signaling and cytokine production, and an
      improvement in insulin sensitivity and body composition. CONCLUSION: While animal
      studies showed a marked tendency towards TLR2 and 4 down-regulation after chronic
      endurance exercise, the current evidence in human is not sufficiently robust to
      conclude any role of TLR in the anti-inflammatory properties of exercise.

PMID- 29461970
TI  - Aerobic exercise inhibits acute lung injury: from mouse to human evidence
      Exercise reduced lung injury markers in mouse and in cells.
AB  - Acute respiratory distress syndrome (ARDS) is defined as hypoxemic respiratory
      failure with intense pulmonary inflammation, involving hyperactivation of
      endothelial cells and neutrophils. Given the anti-inflammatory effects of aerobic
      exercise (AE), this study investigated whether AE performed daily for 5 weeks
      would inhibit extra-pulmonary LPS-induced ARDS. C57Bl/6 mice were distributed
      into Control, Exercise, LPS and Exercise+LPS groups. AE was performed on a
      treadmill for 5x/week for four weeks before LPS administration. 24hours after the
      final AE physical test, animals received 100ug of LPS intra-peritoneally. In
      addition, whole blood cell culture, neutrophils and human endothelial cells were
      preincubated with IL-10, an anti-inflammatory cytokine induced by exercise. AE
      reduced total protein levels (p<0.01) and neutrophil accumulation in
      bronchoalveolar lavage (BAL) (p<0.01) and lung parenchyma (p<0.01). AE reduced
      BAL inflammatory cytokines IL-1beta, IL-6 and GM-CSF (p<0.001), CXCL1/KC, IL-17,
      TNF-alpha and IGF-1 (p<0.01). Systemically, AE reduced IL-1beta, IL-6 and IFN
      gamma (p<0.001), CXCL1/KC (p<0.01) and TNF-alpha (p<0.05). AE increased IL-10
      levels in serum (p<0.001) and BAL (p<0.001). Furthermore, AE increased superoxide
      dismutase SOD (p<0.01) and decreased superoxide anion accumulation in the lungs
      (p<0.01). Lastly, pre-incubation with IL-10 significantly reduced LPS-induced
      activation of whole blood cells, neutrophils and HUVECs, as observed by reduced
      production of IL-1beta, IL-6, IL-8 and TNF-alpha. Our data suggest that AE
      inhibited LPS-induced lung inflammation by attenuating inflammatory cytokines and
      oxidative stress markers in mice and human cell culture via enhanced IL-10
      production.

PMID- 29461971
TI  - Microparticles and Exercise in Clinical Populations.
AB  - Microparticles (MPs) are shed membrane vesicles released from a variety of cell
      types in response to cellular activation or apoptosis. They are elevated in a
      wide variety of disease states and have been previously measured to assess both
      disease activity and severity. However, recent research suggests that they also
      possess bioeffector functions, including but not limited to promoting coagulation
      and thrombosis, inducing endothelial dysfunction, increasing pro-inflammatory
      cytokine release and driving angiogenesis, thereby increasing cardiovascular
      risk. Current evidence suggests that exercise may reduce both the number and
      pathophysiological potential of circulating MPs, making them an attractive
      therapeutic target. However, the existing body of literature is largely comprised
      of in vitro or animal studies and thus drawing meaningful conclusions with
      regards to health and disease remains difficult. In this review, we highlight the
      role of microparticles in disease, comment on the use of exercise and dietary
      manipulation as a therapeutic strategy, and suggest future research directions
      that would serve to address some of the limitations present in the research to
      date.

PMID- 29461972
TI  - Diet enriched with fresh coconut decreases blood glucose levels and body weight
      in normal adults.

PMID- 29461973
TI  - Mid-pregnancy cervical length as a risk factor for cesarean section in women with
      twin pregnancies.

PMID- 29461974
TI  - Comparison of k Q factors measured with a water calorimeter in flattening filter
      free (FFF) and conventional flattening filter (cFF) photon beams.
AB  - Recently flattening filter free (FFF) beams became available for application in
      modern radiotherapy. There are several advantages of FFF beams over conventional
      flattening filtered (cFF) beams, however differences in beam spectra at the point
      of interest in a phantom potentially affect the ion chamber response. Beams are
      also non-uniform over the length of a typical reference ion chamber and
      recombination is usually larger. Despite several studies describing FFF beam
      characteristics, only a limited number of studies investigated their effect on k
      Q factors. Some of those studies predicted significant discrepancies in k Q
      factors (0.4% up to 1.0%) if TPR20,10 based codes of practice (CoPs) were to be
      used. This study addresses the question to which extent k Q factors, based on a
      TPR20,10 CoP, can be applied in clinical reference dosimetry. It is the first
      study that compares k Q factors measured directly with an absorbed dose to water
      primary standard in FFF-cFF pairs of clinical photon beams. This was done with a
      transportable water calorimeter described elsewhere. The measurements corrected
      for recombination and beam radial non-uniformity were performed in FFF-cFF beam
      pairs at 6 MV and 10 MV of an Elekta Versa HD for a selection of three different
      Farmer-type ion chambers (eight serial numbers). The ratio of measured k Q
      factors of the FFF-cFF beam pairs were compared with the TPR20,10 CoPs of the NCS
      and IAEA and the %dd(10) x CoP of the AAPM. For the TPR20,10 based CoPs
      differences less than 0.23% were found in k Q factors between the corresponding
      FFF-cFF beams with standard uncertainties smaller than 0.35%, while for the
      %dd(10) x these differences were smaller than 0.46% and within the expanded
      uncertainty of the measurements. Based on the measurements made with the
      equipment described in this study the authors conclude that the k Q factors
      provided by the NCS-18 and IAEA TRS-398 codes of practice can be applied for
      flattening filter free beams without additional correction. However, existing
      codes of practice cannot be applied ignoring the significant volume averaging
      effect of the FFF beams over the ion chamber cavity. For this a corresponding
      volume averaging correction must be applied.

PMID- 29461975
TI  - Effect on growth and osteoblast mineralization of hydroxyapatite-zirconia (HA
      ZrO2) obtained by a new low temperature system.
AB  - Ceramics and bioceramics, such as hydroxyapatite and zirconium, are used in bone
      tissue engineering. Hydroxyapatite has chemical properties similar to bone while
      zirconium offers suitable mechanical properties. The aim of this article is to
      evaluate the ability to support cell growth and osteoblastic mineralization of
      hydroxyapatite-zirconium obtained by a new system based on different low
      temperatures, such as 873 K (HZ600), 923 K (HZ650) and 973 K (HZ700).
      Hydroxyapatite-zirconia obtained by this new system was examined in terms of
      thermogravimetric features and x-ray diffractograms. Furthermore, the ability for
      supporting osteoblast growth and mineralization were analyzed. By x-ray
      diffraction analysis, we clearly demonstrated that no high-temperature processing
      was required. Moreover, it is possible to form tetragonal-zirconium at 923 K.
      Proliferation assays showed that osteoblast growth was not influenced by any of
      the composite evaluated. Regarding the osteogenic marker Col1, a 2-fold increase
      in expression was observed for HZ650 compared to HZ600 and HZ700. Interestingly,
      osteoblasts grown on HZ650 showed globular accretions covered with collagen
      bundles and calcium-rich extracellular matrix whereas HZ600 and HZ700 showed no
      phosphate or calcium deposits. This study demonstrated that at 923 K it is
      possible to generate stable tetragonal-zirconium and the resulting HZ650
      composite is able to promote a suitable osteoblast mineralization process.

PMID- 29461976
TI  - Mycobacterial growth inhibition is associated with trained innate immunity.
AB  - The lack of defined correlates of protection hampers development of vaccines
      against tuberculosis (TB). In vitro mycobacterial outgrowth assays are thought to
      better capture the complexity of the human host/Mycobacterium tuberculosis (Mtb)
      interaction. Here, we used a mycobacterial growth inhibition assay (MGIA) based
      on peripheral blood mononuclear cells to investigate the capacity to control
      outgrowth of bacille Calmette-Guerin (BCG). Interestingly, strong control of BCG
      outgrowth was observed almost exclusively in individuals with recent exposure to
      Mtb, but not in (long-term) latent TB infection, and only modestly in BCG
      vaccinees. Mechanistically, control of mycobacterial outgrowth strongly
      correlated with the presence of a CD14dim monocyte population, but also required
      the presence of T cells. The nonclassical monocytes produced CXCL10, and CXCR3
      receptor blockade inhibited the capacity to control BCG outgrowth. Expression of
      CXCR3 splice variants was altered in recently Mtb-exposed individuals. Cytokines
      previously associated with trained immunity were detected in MGIA supernatants,
      and CXCL9, CXCL10, and CXCL11 represent new markers of trained immunity. These
      data indicate that CXCR3 ligands are associated with trained immunity and are
      critical factors in controlling mycobacterial outgrowth. In conclusion, control
      of mycobacterial outgrowth early after exposure to Mtb is the result of trained
      immunity mediated by a CXCL10-producing nonclassical CD14dim monocyte subset.

PMID- 29461977
TI  - Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to
      targeted therapy.
AB  - BACKGROUND: Sporadic vascular malformations (VMs) are complex congenital
      anomalies of blood vessels that lead to stroke, life-threatening bleeds,
      disfigurement, overgrowth, and/or pain. Therapeutic options are severely limited,
      and multidisciplinary management remains challenging, particularly for high-flow
      arteriovenous malformations (AVM). METHODS: To investigate the pathogenesis of
      sporadic intracranial and extracranial VMs in 160 children in which known genetic
      causes had been excluded, we sequenced DNA from affected tissue and optimized
      analysis for detection of low mutant allele frequency. RESULTS: We discovered
      multiple mosaic-activating variants in 4 genes of the RAS/MAPK pathway, KRAS,
      NRAS, BRAF, and MAP2K1, a pathway commonly activated in cancer and responsible
      for the germline RAS-opathies. These variants were more frequent in high-flow
      than low-flow VMs. In vitro characterization and 2 transgenic zebrafish AVM
      models that recapitulated the human phenotype validated the pathogenesis of the
      mutant alleles. Importantly, treatment of AVM-BRAF mutant zebrafish with the BRAF
      inhibitor vemurafinib restored blood flow in AVM. CONCLUSION: Our findings
      uncover a major cause of sporadic VMs of different clinical types and thereby
      offer the potential of personalized medical treatment by repurposing existing
      licensed cancer therapies. FUNDING: This work was funded or supported by grants
      from the AVM Butterfly Charity, the Wellcome Trust (UK), the Medical Research
      Council (UK), the UK National Institute for Health Research, the L'Oreal-Melanoma
      Research Alliance, the European Research Council, and the National Human Genome
      Research Institute (US).

PMID- 29461978
TI  - Surface receptor Toso controls B cell-mediated regulation of T cell immunity.
AB  - The immune system is tightly controlled by regulatory processes that allow for
      the elimination of invading pathogens, while limiting immunopathological damage
      to the host. In the present study, we found that conditional deletion of the cell
      surface receptor Toso on B cells unexpectedly resulted in impaired
      proinflammatory T cell responses, which led to impaired immune protection in an
      acute viral infection model and was associated with reduced immunopathological
      tissue damage in a chronic inflammatory context. Toso exhibited its B cell
      inherent immunoregulatory function by negatively controlling the pool of IL-10
      competent B1 and B2 B cells, which were characterized by a high degree of self
      reactivity and were shown to mediate immunosuppressive activity on inflammatory T
      cell responses in vivo. Our results indicate that Toso is involved in the
      differentiation/maintenance of regulatory B cells by fine-tuning B cell receptor
      activation thresholds. Furthermore, we showed that during influenza A-induced
      pulmonary inflammation, the application of Toso-specific antibodies selectively
      induced IL-10-competent B cells at the site of inflammation and resulted in
      decreased proinflammatory cytokine production by lung T cells. These findings
      suggest that Toso may serve as a novel therapeutic target to dampen pathogenic T
      cell responses via the modulation of IL-10-competent regulatory B cells.

PMID- 29461982
TI  - Immune-mediated Pericarditis With Pericardial Tamponade During Nivolumab Therapy.
AB  - A 69-year-old man with metastatic lung adenocarcinoma presented with pericarditis
      and pericardial tamponade during nivolumab treatment, despite near-complete
      response on images performed during response evaluation. Further investigation
      found no evidence of pericardial or pleural cancer involvement, and pathologic
      evaluation showed immune-related adverse effect. Surgical and steroid treatments
      were used, with excellent results, and no disease progression on follow-up
      despite drug discontinuation because of toxicity. Although life-threatening
      immune-related adverse effects are not frequent when using checkpoint inhibitors,
      and cardiotoxicity is very rare, different clinical manifestations may occur, and
      some of them can be fatal in case of inadequate management. It may be challenging
      to make an etiological diagnosis; however, favorable outcomes can be achieved
      when prompt directed treatment is promoted.

PMID- 29461981
TI  - CYP3A4 mutation causes vitamin D-dependent rickets type 3.
AB  - Genetic forms of vitamin D-dependent rickets (VDDRs) are due to mutations
      impairing activation of vitamin D or decreasing vitamin D receptor
      responsiveness. Here we describe two unrelated patients with early-onset rickets,
      reduced serum levels of the vitamin D metabolites 25-hydroxyvitamin D and 1,25
      dihydroxyvitamin D, and deficient responsiveness to parent and activated forms of
      vitamin D. Neither patient had a mutation in any genes known to cause VDDR;
      however, using whole exome sequencing analysis, we identified a recurrent de novo
      missense mutation, c.902T>C (p.I301T), in CYP3A4 in both subjects that alters the
      conformation of substrate recognition site 4 (SRS-4). In vitro, the mutant CYP3A4
      oxidized 1,25-dihydroxyvitamin D with 10-fold greater activity than WT CYP3A4 and
      2-fold greater activity than CYP24A1, the principal inactivator of vitamin D
      metabolites. As CYP3A4 mutations have not previously been linked to rickets,
      these findings provide insight into vitamin D metabolism and demonstrate that
      accelerated inactivation of vitamin D metabolites represents a mechanism for
      vitamin D deficiency.

PMID- 29461979
TI  - Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized
      mice.
AB  - The discovery of an HIV-1 cure remains a medical challenge because the virus
      rebounds quickly after the cessation of combination antiretroviral therapy
      (cART). Here, we investigate the potential of an engineered tandem bispecific
      broadly neutralizing antibody (bs-bnAb) as an innovative product for HIV-1
      prophylactic and therapeutic interventions. We discovered that by preserving 2
      single-chain variable fragment (scFv) binding domains of each parental bnAb, a
      single gene-encoded tandem bs-bnAb, BiIA-SG, displayed substantially improved
      breadth and potency. BiIA-SG neutralized all 124 HIV-1-pseudotyped viruses
      tested, including global subtypes/recombinant forms, transmitted/founder viruses,
      variants not susceptible to parental bnAbs and to many other bnAbs with an
      average IC50 value of 0.073 MUg/ml (range < 0.001-1.03 MUg/ml). In humanized
      mice, an injection of BiIA-SG conferred sterile protection when administered
      prior to challenges with diverse live HIV-1 stains. Moreover, whereas BiIA-SG
      delayed viral rebound in a short-term therapeutic setting when combined with
      cART, a single injection of adeno-associated virus-transferred (AAV-transferred)
      BiIA-SG gene resulted dose-dependently in prolonged in vivo expression of BiIA
      SG, which was associated with complete viremia control and subsequent elimination
      of infected cells in humanized mice. These results warrant the clinical
      development of BiIA-SG as a promising bs-bnAb-based biomedical intervention for
      the prevention and treatment of HIV-1 infection.

PMID- 29461983
TI  - Corticosterone impairs flexible adjustment of spatial navigation in an
      associative place-reward learning task.
AB  - Cognitive challenges are often accompanied by a discharge of stress hormones,
      which in turn modulate multiple brain areas. Among these, the medial temporal
      lobe and the prefrontal cortex are critically involved in high-order cognitive
      functions such as learning, memory, and decision-making. Previous studies
      assessing the effects of corticosterone on spatial memory found an increase or a
      decrease in performance depending on the timing of stress hormone discharge
      relative to the behavioral task. Most of these studies, however, made use of
      aversively motivated behaviors, whereas less is known about corticosteroid
      effects on flexible learning during reward-driven spatial navigation. To study
      how corticosterone modulates flexible spatial learning, we tested rats on a place
      reward association task where hormone treatment was administered immediately
      after a session presenting a change in reward locations. The corticosterone
      treated group showed delayed learning during the initial sessions and suboptimal
      memory consolidation throughout testing. Repeated training on the novel reward
      positions improved performance and eliminated differences from the control group.
      We conclude that a marked increase in plasma corticosterone levels immediately
      after training impairs the flexible formation of new place-reward associations.

PMID- 29461984
TI  - Thrombosis and Thromboprophylaxis in Gynecology Surgery.
AB  - Gynecologic surgery offers unique challenges, as pelvic surgery places patients
      at an increased risk of venous thromboembolism (VTE). Prevention of VTE is a goal
      of patients, policy makers, and surgeons. In this review, we address the current
      research and recommendations for VTE prophylaxis.

PMID- 29461986
TI  - Bicondylar Tibial Plateau Fractures: A Critical Analysis Review.

PMID- 29461980
TI  - Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57
      protection against HIV-1.
AB  - HLA-B*57 control of HIV involves enhanced CD8+ T cell responses against infected
      cells, but extensive heterogeneity exists in the level of HIV control among B*57+
      individuals. Using whole-genome sequencing of untreated B*57+ HIV-1-infected
      controllers and noncontrollers, we identified a single variant (rs643347A/G)
      encoding an isoleucine-to-valine substitution at position 47 (I47V) of the
      inhibitory killer cell immunoglobulin-like receptor KIR3DL1 as the only
      significant modifier of B*57 protection. The association was replicated in an
      independent cohort and across multiple outcomes. The modifying effect of I47V was
      confined to B*57:01 and was not observed for the closely related B*57:03.
      Positions 2, 47, and 54 tracked one another nearly perfectly, and 2 KIR3DL1
      allotypes differing only at these 3 positions showed significant differences in
      binding B*57:01 tetramers, whereas the protective allotype showed lower binding.
      Thus, variation in an immune NK cell receptor that binds B*57:01 modifies its
      protection. These data highlight the exquisite specificity of KIR-HLA
      interactions in human health and disease.

PMID- 29461985
TI  - Adult and Adolescent Patient Evaluations of Electroconvulsive Therapy in
      Comparison to Other Therapeutic Modalities.
AB  - OBJECTIVES: There is an increasing awareness of the importance of patients'
      subjective evaluations of therapy. Regarding electroconvulsive therapy (ECT), the
      results are conflicting. We hypothesized that making a comparison between
      patients' satisfaction with ECT and other forms of psychiatric therapies would
      capture personal experience as opposed to opinion about the treatment modalities.
      We compared adult responses to adolescent responses. METHODS: Four unmatched
      patient groups were recruited (N = 98) and were divided as follows: (a) patients
      treated with ECT as adolescents (n = 13), (b) patients treated with ECT as adults
      (n = 25), (c) patients hospitalized as adolescents but not treated with ECT (n =
      30), and (d) patients hospitalized as adults but not treated with ECT (n = 30).
      All patients were interviewed using similar questions related to their
      satisfaction regarding the treatment modalities they experienced, including
      psychotherapy, pharmacotherapy, hospitalization and ECT, and years after being
      treated. RESULTS: Adults and adolescents viewed ECT as a legitimate and effective
      form of treatment (70%). Patients who were treated with ECT had a more positive
      attitude toward this treatment compared with patients who had not been treated
      with ECT. In comparison to other treatment modalities, ECT was considered by both
      adolescents and adults as the least effective form of therapy. Psychotherapy was
      considered the most effective, specifically among adolescents. CONCLUSIONS:
      Comparing patients' satisfaction in regard to different therapeutic modalities
      can potentially help clarify discrepancies in patient reports on satisfaction
      with ECT. Patients' satisfaction with ECT, just like their clinical response to
      ECT, is more dichotomous than with other forms of therapy.

PMID- 29461987
TI  - Autologous Chondrocyte Implantation (ACI) for Knee Cartilage Defects: A Review of
      Indications, Technique, and Outcomes.

PMID- 29461988
TI  - Strategies to Contain Cost Associated with Orthopaedic Care.

PMID- 29461990
TI  - Powering Up with Technology to Deliver Transformative Care and Lower Costs.

PMID- 29461989
TI  - Participants' Experiences of a Sexual Counseling Intervention During Cardiac
      Rehabilitation: A Nested Qualitative Study Within the CHARMS Pilot Randomized
      Controlled Trial.
AB  - BACKGROUND: International guidelines recommend sexual assessment and counseling
      be offered to all patients with cardiovascular disease during cardiac
      rehabilitation. However, sexual problems are infrequently addressed. The Cardiac
      Health and Relationship Management and Sexuality (CHARMS) intervention is a
      complex, multilevel intervention designed to increase the provision of sexual
      counseling in cardiac rehabilitation. It was piloted in 2 cardiac rehabilitation
      centers to assess the acceptability and feasibility of the intervention and to
      inform and refine a definitive cluster randomized controlled trial protocol.
      OBJECTIVES: The aim of this study was to explore the experiences, perceptions,
      and opinions of patients, partners, and cardiac rehabilitation staff who
      participated in the CHARMS staff-led patient education class. METHODS: A
      qualitative, descriptive study using semistructured interviews to collect the
      data. Cardiac rehabilitation staff (n = 8) were interviewed when the intervention
      commenced in their center and 3 months later (n = 6). Patients (n = 19) and
      partners (n = 2) were interviewed after delivery of the class; 7 were interviewed
      again 3 months postintervention to explore temporal changes in opinions. RESULTS:
      Most cardiac rehabilitation staff were comfortable delivering the CHARMS
      intervention but would prefer a less structured format. Some staff perceived
      discomfort among patients. Few patients reported discomfort. Most patients and
      partners considered that the intervention was a welcome and acceptable part of a
      cardiac rehabilitation program. CONCLUSION: Incorporating sexual counseling into
      cardiac rehabilitation programs is feasible. Although the views of the patients
      and staff diverged on a number of issues including the perceived comfort of
      patients, its inclusion was welcomed by patients and was acceptable overall to
      both staff and patients.

PMID- 29461991
TI  - Technology's Role in Quality Improvement and Operational Efficiency.
AB  - Technology for technology's sake is never a good idea. There must be a purpose
      behind it. It must help us do our jobs better. Technology allows healthcare to
      remain affordable and, as such, accessible. Technology must increase access to
      care, improve safety, make test results more reliable, and help teams communicate
      better for a seamless care experience.Avera Health, a health system based in
      Sioux Falls, South Dakota, comprises 330 facilities in 100 communities in five
      states. Sponsored by the Benedictine and Presentation Sisters, Avera is a
      healthcare ministry whose employees deliver high-quality care with compassion. We
      have been early innovators in using technology to deliver a high standard of
      service.Avera has been nationally recognized for its innovation. For 18 of the
      past 19 years, the system has been named to Hospitals & Health Networks
      magazine's list of Health Care's Most Wired and has been designated as "advanced"
      for reasons that include the development of the most extensive telehealth network
      serving rural healthcare facilities. Avera also won the Most Wired Innovator
      Award in 2011 and 2012. Avera's flagship 545-bed tertiary facility, Avera
      McKennan Hospital & University Health Center, has received Stage 7 recognition
      from HIMSS Analytics.Avera leaders have developed a spirit of inquiry and a
      culture of innovation. We have fostered change by aligning our care into service
      lines that help ensure that wherever people walk in our doors, they will receive
      the same quality care. In several cases, we have innovated through strategic
      partnerships. In this article, we describe how technology helps sustain our
      culture of innovation.

PMID- 29461992
TI  - Healthcare's Future: Strategic Investment in Technology.
AB  - Recent and rapid advances in the implementation of technology have greatly
      affected the quality and efficiency of healthcare delivery in the United States.
      Simultaneously, diverse generational pressures-including the consumerism of
      millennials and unsustainable growth in the costs of care for baby boomers-have
      accelerated a revolution in healthcare delivery that was marked in 2010 by the
      passage of the Affordable Care Act.Against this backdrop, Maryland and the
      Centers for Medicare & Medicaid Services entered into a partnership in 2014 to
      modernize the Maryland All-Payer Model. Under this architecture, each Maryland
      hospital negotiates a global budget revenue agreement with the state's rate
      setting agency, limiting the hospital's annual revenue to the budgetary cap
      established by the state.At Atlantic General Hospital (AGH), leaders had
      established a disciplined strategic planning process in which the board of
      trustees, medical staff, and administration annually agree on goals and
      initiatives to achieve the objectives set forth in its five-year strategic plans.
      This article describes two initiatives to improve care using technology. In 2006,
      AGH introduced a service guarantee in the emergency room (ER); the ER 30-Minute
      Promise assures patients that they will be placed in a bed or receive care within
      30 minutes of arrival in the ER. In 2007, several independent hospitals in the
      state formed Maryland eCare to jointly contract for intensive care unit (ICU)
      physician coverage via telemedicine. This technology allows clinical staff to
      continuously monitor ICU patients remotely. The positive results of the ER 30
      Minute Promise and Maryland eCare program show that technological advances in an
      independent, small, rural hospital can make a significant impact on its ability
      to maintain independence. AGH's strategic investments prepared the organization
      well for the transition in 2014 to a value-based payment system.

PMID- 29461993
TI  - Optimizing Technology and Business Intelligence with Data Governance.

PMID- 29461994
TI  - Finding New Ways to Meet the Expectations of Patients and Staff.

PMID- 29461995
TI  - Harnessing Technology Innovation to Improve Patient Care.

PMID- 29461996
TI  - Caregivers' Priorities and Observed Outcomes of Attention-Deficit Hyperactivity
      Disorder Medication for Their Children.
AB  - OBJECTIVE: To document variability among caregivers' priorities when considering
      medication to treat their Children's attention-deficit hyperactivity disorder
      (ADHD) and explore associations between these priorities and medication-related
      improvements. METHODS: Caregivers of children, ages 4 to 14 years, diagnosed with
      ADHD were recruited from outpatient clinics and support groups across Maryland. A
      survey gathered data on caregiver-reported concerns when considering ADHD
      medication, demographic characteristics, and observed and desired improvements in
      their child's ADHD. A validated Best-Worst Scaling instrument assessed priorities
      among 16 concerns when considering ADHD medication. Latent class analysis
      identified subgroups with similar ADHD medication concerns. Differences in self
      reported medication-related improvements were examined across subgroups. RESULTS:
      The 184 participants (mean = 42 yrs) were primarily the biological mother, 68%
      white and 25% black. Their children were mostly male (73%) and using medication
      (81%). Overall, the most important ADHD medication concerns were the child
      becoming a successful adult (p < 0.0001), school behavior improvements (p <
      0.0001), and better grades (p < 0.0001). Others thinking badly of the child was a
      significantly less important concern (p < 0.0001). Three subgroups were
      identified: short-term outcomes-oriented group (39%), long-term outcomes-oriented
      group (37%), and side effects/safety-oriented group (27%). Relative to the other
      2 groups, a smaller proportion of the side effects/safety-oriented group desired
      these improvements (p < 0.2618). CONCLUSION: Most caregivers prioritize short-
      and long-term outcomes when considering ADHD medication. However, those most
      concerned with long- or short-term outcomes tended to desire additional
      improvements in their child's ADHD.

PMID- 29461997
TI  - Best-Worst Scaling to Prioritize Outcomes Meaningful to Caregivers of Youth with
      Mental Health Multimorbidities: A Pilot Study.
AB  - OBJECTIVE: Health care decision-making for youth with mental health
      multimorbidity is guided by outcomes that are considered most meaningful and
      important. The study objective was to pilot test a best-worst scaling (BWS)
      instrument designed to assess trade-offs among caregiver-defined, meaningful
      health care outcomes. METHODS: A BWS was designed with continuous stakeholder
      involvement to elicit caregiver-defined outcomes in 4 domains: school,
      behavioral, social, and independence. Four attributes were identified for each
      outcome domain, for a total of 16 attributes. Using a balanced incomplete block
      design, a BWS instrument was developed with 16 choice task questions displaying 6
      attributes at a time. A convenience sample was selected from Maryland caregivers
      of children who were 21 years old or younger and had a developmental delay and a
      comorbid mental health condition. Participants completed a survey that included
      demographics and the BWS instrument. Conditional logit was used to estimate
      utility scores and 95% confidence intervals (CI) for each attribute, which were
      ranked in order of importance. Attribute statements were refined after a
      respondent debriefing session. RESULTS: A total of 38 caregivers participated in
      the pilot study. Child safety to self was the most important outcome (1.01, CI,
      0.78-1.24). This was followed by securing support for an Individualized
      educational plan in school (0.77, CI, 0.54-1.01) and the child being able to stay
      in school all day (0.53, CI, 0.29-0.77). CONCLUSION: BWS scenarios that resemble
      real-life decision-making can be a useful tool to identify preferences for health
      care outcomes.

PMID- 29461998
TI  - Commentary on Same-Sex and Different-Sex Parent Households and Child Health
      Outcomes: Additional Sources of Same-Sex Parenting Stress to Consider.

PMID- 29461999
TI  - Successful Use of Leukocyte Platelet-Rich Fibrin in the Healing of Sinus Membrane
      Perforation: A Case Report.
AB  - PURPOSE: The aim of this case report was to demonstrate the repair of a large
      sinus membrane perforation related to a sinus floor augmentation procedure, using
      leukocyte platelet-rich fibrin (L-PRF), for subsequent rehabilitation of a
      partially edentulous patient. MATERIALS AND METHODS: The patient presented the
      absence of teeth numbers 18, 17, and 16, associated with insufficient bone height
      because of the maxillary sinus pneumatization. A maxillary inlay bone graft was
      proposed, however, during the sinus floor augmentation procedure, a large portion
      of the sinus membrane was ruptured. To avoid interruption of the surgical
      procedure, membrane mending was proposed using L-PRF and collagen membranes.
      RESULTS: After 8 months, 2 external hexagon connection dental implants were
      placed in the 16 and 17 teeth regions, and a screw-retained implant-supported
      prosthesis was installed. CONCLUSION: The use of L-PRF associated with collagen
      membrane was efficient for the sealing of the sinus membrane perforation and
      enabled bone formation for subsequent implant installation.

PMID- 29462000
TI  - Clinical Burdens of beta-Thalassemia Major in Affected Children.
AB  - BACKGROUND: beta-thalassemia major (BTM) is an inherited blood disorder leading
      to severe anemia. A better understanding of BTM complications can be considered
      an important factor in developing effective health care provision. METHOD: A
      descriptive exploratory design was used to identify the clinical burden of BTM
      from affected children's perspective. A convenience sample of 45 patients with
      BTM, accompanied by a family member, was recruited from a governmental hospital
      during April-May 2015. RESULTS: The most reported clinical burden was facial
      deformity 86.9%, followed by systematic infection (48.8%), growth delay (44.4%),
      and liver problems (39.9%). Patient age was significantly associated with
      clinical burdens such as bone pain and facial deformity. The number of blood
      transfusions received was associated with growth delay and bone pain. CONCLUSION:
      This study highlights the clinical burdens of thalassemia on affected children,
      in terms of physical appearance, growth delay and other burdens.

PMID- 29462001
TI  - Infantile Osteopetrosis.

PMID- 29462002
TI  - An In-Vitro Insertion-Force Study of Magnetically Guided Lateral-Wall Cochlear
      Implant Electrode Arrays: Erratum.

PMID- 29462003
TI  - Toll Like Receptor 4 Signaling Licenses the Cytosolic Transport of
      Lipopolysaccharide from Bacterial Outer Membrane Vesicles.
AB  - Outer membrane vesicles (OMVs), released by variety of bacteria, are membrane
      enclosed entities enriched in microbial components, toxins and virulent factors.
      OMVs could deliver lipopolysaccharide (LPS) into the cytosol of host cells and
      subsequently activate caspase-11, which critically orchestrates immune responses
      and mediates septic shock. Though it is known that caspase-11 is activated by
      intracellular LPS, how OMVs deliver LPS into the cytosol remains largely unknown.
      Here we show that the activation of toll like receptor 4 (TLR4), a LPS receptor
      on the cytoplasmic membrane, licenses macrophages to transport LPS from OMVs into
      the cytosol through TIR domain-containing adaptor-inducing interferon-beta
      (TRIF). TRIF-mediated cytosolic delivery of LPS from OMVs depends on the
      production of type 1 interferon and the expression of guanylate-binding proteins
      (GBPs). Deletion of TRIF or GBPs prevents pyroptosis and lethality induced by
      OMVs or OMVs-releasing E.coli. Together, these findings provide novel insight
      into how host coordinates extracellular and intracellular LPS sensing to
      orchestrate immune responses during gram-negative bacterial infection.

PMID- 29462004
TI  - How Surrogate Decision-Makers for Patients With Chronic Critical Illness Perceive
      and Carry Out Their Role.
AB  - OBJECTIVES: Family members commonly make medical decision for patients with
      chronic critical illness. This study examines how family members approach this
      decision-making role in real time. DESIGN: Qualitative analysis of interviews
      with family members in the intervention arm of a randomized controlled
      communication trial. SETTINGS: Medical ICUs at four U.S. hospitals. PARTICIPANTS:
      Family members of patients with chronic critical illness (adults mechanically
      ventilated for >= 7 d and expected to remain ventilated and survive for >= 72 hr)
      who participated in the active arm of a communication intervention study.
      INTERVENTIONS: Family members participated in at least two content-guided,
      informational, and emotional support meetings led by a palliative care physician
      and nurse practitioner. MEASUREMENTS AND MAIN RESULTS: Grounded theory was used
      for qualitative analysis of 66 audio recordings of meetings with 51 family
      members. Family members perceived their role in four main ways: voice of the
      patient, advocate for the patient, advocate for others, and advocate for oneself.
      Their decision-making was characterized by balancing goals, sharing their role,
      keeping perspective, remembering previous experiences, finding sources of
      strength, and coping with various burdens. CONCLUSIONS: Family members take a
      multifaceted approach as they participate in decision-making. Understanding how
      surrogates perceive and act in their roles may facilitate shared decision-making
      among clinicians and families during critical care.

PMID- 29462005
TI  - Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus
      Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A
      Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial.
AB  - OBJECTIVE: This study was performed to determine whether neoadjuvant treatment
      increases survival in patients with BRPC. SUMMARY BACKGROUND DATA: Despite many
      promising retrospective data on the effect of neoadjuvant treatment for
      borderline resectable pancreatic cancer (BRPC), no high-level evidence exists to
      support the role of such treatment. METHODS: This phase 2/3 multicenter
      randomized controlled trial was designed to enroll 110 patients with BRPC who
      were randomly assigned to gemcitabine-based neoadjuvant chemoradiation treatment
      (54 Gray external beam radiation) followed by surgery or upfront surgery followed
      by chemoradiation treatment from four large-volume centers in Korea. The primary
      endpoint was the 2-year survival rate (2-YSR). Interim analysis was planned at
      the time of 50% case enrollment. RESULTS: After excluding the patients who
      withdrew consent (n = 8) from the 58 enrolled patients, 27 patients were
      allocated to neoadjuvant treatment and 23 to upfront surgery groups. The overall
      2-YSR was 34.0% with a median survival of 16 months. In the intention-to-treat
      analysis, the 2-YSR and median survival were significantly better in the
      neoadjuvant chemoradiation than the upfront surgery group [40.7%, 21 months vs
      26.1%, 12 months, hazard ratio 1.495 (95% confidence interval 0.66-3.36), P =
      0.028]. R0 resection rate was also significantly higher in the neoadjuvant
      chemoradiation group than upfront surgery (n = 14, 51.8% vs n = 6, 26.1%, P =
      0.004). The safety monitoring committee decided on early termination of the study
      on the basis of the statistical significance of neoadjuvant treatment efficacy.
      CONCLUSION: This is the first prospective randomized controlled trial on the
      oncological benefits of neoadjuvant treatment in BRPC. Compared to upfront
      surgery, neoadjuvant chemoradiation provides oncological benefits in patients
      with BRPC.

PMID- 29462006
TI  - A Combination of Robotic Approach and ERAS Pathway Optimizes Outcomes and Cost
      for Pancreatoduodenectomy.
AB  - OBJECTIVE: To determine the impact of enhanced recovery after surgery (ERAS)
      pathway implementation on outcomes, and cost of robotic and open
      pancreatoduodenectomy. BACKGROUND: ERAS pathways have shown benefit in open
      pancreatoduodenectomy (OPD). The impact of ERAS on robotic pancreatoduodenectomy
      (RPD) is unknown. METHODS: Retrospective review of consecutive RPD and OPDs in
      the pre-ERAS (July, 2014-July, 2015) and ERAS (July, 2015-July, 2016) period.
      Univariate and multivariate logistic regression was used to determine impact of
      ERAS and operative approach alone, or in combination (pre-ERAS + OPD, pre-ERAS +
      RPD, ERAS + OPD, ERAS + RPD) on length of hospital stay (LOS) and overall cost.
      RESULTS: In all, 254 consecutive pancreatoduodenectomies (RPD 62%, OPD 38%) were
      analyzed (median age 67, 47% female). ERAS patients had shorter LOS (6 vs 8 days;
      P = 0.004) and decreased overall cost (USD 20,362 vs 24,277; P = 0.001) compared
      with non-ERAS patients, whereas RPD was associated with decreased LOS (7 vs 8
      days; P = 0.0001) and similar cost compared with OPD. On multivariable analysis
      (MVA), RPD was predictive of shorter LOS [odds ratio (OR) 0.33, confidence
      interval (CI) 0.16-0.67, P = 0.002), whereas ERAS was protective against high
      cost (OR 0.57, CI 0.33-0.97, P = 0.037). On MVA, when combining operative
      approach with ERAS pathway use, a combined ERAS + RPD approach was associated
      with reduced LOS and optimal cost compared with other combinations (pre-ERAS +
      OPD, pre-ERAS + RPD, ERAS + OPD). CONCLUSION: ERAS implementation is
      independently associated with cost savings for pancreatoduodenectomy. A
      combination of ERAS and robotic approach synergistically decreases hospital stay
      and overall cost compared with other strategies.

PMID- 29462007
TI  - Risk Factors for Recurrence After Treatment of N1b Papillary Thyroid Carcinoma.
AB  - OBJECTIVES: To examine risk factors for posttreatment recurrence in papillary
      thyroid carcinoma (PTC) patients with initial presentation of lateral neck
      metastasis (N1b). SUMMARY OF BACKGROUND DATA: N1b PTC recurs after definitive
      treatment. METHODS: Study subjects were 437 consecutive PTC patients who
      underwent total thyroidectomy and therapeutic neck dissection of central and
      lateral compartments and postoperative radioactive iodine ablation therapy. The
      patients' demographics and pathological factors, including factors related to
      tumors and lymph nodes (LNs), and postoperative thyroglobulin levels were
      reviewed. Univariate and multivariate Cox proportional hazards regression
      analyses were used to identify factors associated with recurrence-free survival
      (RFS). RESULTS: During a median follow-up of 83 months (range, 32-135 months),
      recurrence occurred in 81 (18.1%) patients. Univariate analyses showed that male
      sex, tumor size, macroscopic extrathyroidal extension, perineural invasion,
      extranodal extension, LN involvement, LN ratio, MACIS score, and postoperative
      serum levels of thyroglobulin were significantly associated with RFS (P < 0.05).
      Multivariate analyses revealed that LN ratio (> 0.25) in the lateral compartment
      (adjusted hazard ratio = 2.099, 95% confidence interval = 1.278-3.448; P =
      0.003), and postoperative serum levels of stimulated (>5.0 ng/mL; 3.172, 1.661
      6.056, P < 0.001) and unstimulated (>0.1 ng/mL; 3.200, 1.569-6.526, P = 0.001)
      thyroglobulin were independent predictors of any-site RFS. Clinical and tumor
      factors were not independent predictors of RFS outcomes (P > 0.1). CONCLUSIONS:
      Posttreatment recurrence is predicted by the LN ratio in the lateral compartment
      and postoperative serum levels of thyroglobulin in patients with metastatic PTC
      in the lateral neck.

PMID- 29462008
TI  - Opioid Overdose-the Surgeon's Role.
AB  - : With increased focus on the potential harms of surgical opioid prescribing,
      surgeons should be cognizant of the risk of opioid-related adverse events in
      their patients, including overdose. Risk factors for overdose may be more
      prevalent than surgeons think, and include high current opioid use, previous or
      existing substance use disorder, history of overdose, or certain medical
      comorbidities. The first step to protecting surgical patients from opioid
      overdose is adequate screening for risk factors; appropriate patient counseling
      and prudent prescribing practices can then help protect at-risk patients.

PMID- 29462009
TI  - Gender Differences in Utilization of Duty-hour Regulations, Aspects of Burnout,
      and Psychological Well-being Among General Surgery Residents in the United
      States.
AB  - OBJECTIVE: The aim of the study was to (1) assess differences in how male and
      female general surgery residents utilize duty-hour regulations and experience
      aspects of burnout and psychological well-being, and (2) to explore reasons why
      these differing experiences exist. BACKGROUND: There may be differences in how
      women and men enter, experience, and leave residency programs. METHODS: A total
      of 7395 residents completed a survey (response rate = 99%). Logistic regression
      models were developed to examine the association between gender and resident
      outcomes. Semistructured interviews were conducted with 42 faculty and 56
      residents. Transcripts were analyzed thematically using a constant comparative
      approach. RESULTS: Female residents reported more frequently staying in the
      hospital >28 hours or working >80 hours in a week (>=3 times in a month, P <
      0.001) and more frequently feeling fatigued and burned out from their work (P <
      0.001), but less frequently "treating patients as impersonal objects" or "not
      caring what happens" to them (P < 0.001). Women reported more often having
      experienced many aspects of poor psychological well-being such as feeling unhappy
      and depressed or thinking of themselves as worthless (P < 0.01). In adjusted
      analyses, associations remained significant. Themes identified in the qualitative
      analysis as possible contributory factors to gender differences include a lack of
      female mentorship/leadership, dual-role responsibilities, gender blindness, and
      differing pressures and approaches to patient care. CONCLUSIONS: Female residents
      report working more, experiencing certain aspects of burnout more frequently, and
      having poorer psychological well-being. Qualitative themes provide insights into
      possible cultural and programmatic shifts to address the concerns for female
      residents.

PMID- 29462010
TI  - ERAS Implementation-Time To Move Forward.

PMID- 29462011
TI  - Positive End-expiratory Pressure Alone Minimizes Atelectasis Formation in
      Nonabdominal Surgery: A Randomized Controlled Trial.
AB  - BACKGROUND: Various methods for protective ventilation are increasingly being
      recommended for patients undergoing general anesthesia. However, the importance
      of each individual component is still unclear. In particular, the perioperative
      use of positive end-expiratory pressure (PEEP) remains controversial. The authors
      tested the hypothesis that PEEP alone would be sufficient to limit atelectasis
      formation during nonabdominal surgery. METHODS: This was a randomized controlled
      evaluator-blinded study. Twenty-four healthy patients undergoing general
      anesthesia were randomized to receive either mechanical ventilation with PEEP 7
      or 9 cm H2O depending on body mass index (n = 12) or zero PEEP (n = 12). No
      recruitment maneuvers were used. The primary outcome was atelectasis area as
      studied by computed tomography in a transverse scan near the diaphragm, at the
      end of surgery, before emergence. Oxygenation was evaluated by measuring blood
      gases and calculating the ratio of arterial oxygen partial pressure to inspired
      oxygen fraction (PaO2/FIO2 ratio). RESULTS: At the end of surgery, the median
      (range) atelectasis area, expressed as percentage of the total lung area, was 1.8
      (0.3 to 9.9) in the PEEP group and 4.6 (1.0 to 10.2) in the zero PEEP group. The
      difference in medians was 2.8% (95% CI, 1.7 to 5.7%; P = 0.002). Oxygenation and
      carbon dioxide elimination were maintained in the PEEP group, but both
      deteriorated in the zero PEEP group. CONCLUSIONS: During nonabdominal surgery,
      adequate PEEP is sufficient to minimize atelectasis in healthy lungs and thereby
      maintain oxygenation. Thus, routine recruitment maneuvers seem unnecessary, and
      the authors suggest that they should only be utilized when clearly indicated.
      VISUAL ABSTRACT: An online visual overview is available for this article at
      http://links.lww.com/ALN/B728.

PMID- 29462013
TI  - Patient Acceptance of Sustained Glaucoma Treatment Strategies.
AB  - PURPOSE: To assess patient acceptance of different methods for delivering
      sustained-release, intraocular pressure (IOP)-lowering medications. METHODS:
      Electronic surveys were administered to 150 patients at 2 glaucoma clinics.
      Participants were questioned on their willingness to accept: (1) drug-eluting
      contact lenses, (2) ring inserts (3) punctal plugs, and (4) subconjunctival
      injections as alternatives to IOP-lowering eye drops based on various success
      levels. Multivariable logistic regression models determined the association
      between device type and treatment acceptance adjusting for age, sex, study site,
      cost burden of drops, and previous contact lens use. RESULTS: The majority (69%)
      of participants were 55 to 74 years of age, and white (65%), and half were
      female. The majority of participants would accept contacts (59%), rings (51%),
      plugs (57%), and subconjunctival injections (52%) if they obviated glaucoma
      surgery; fewer would accept these devices if they reduced (23% to 35%) or
      eliminated (27% to 42%) drops. Most participants would also accept contacts
      (56%), plugs (55%), and subconjunctival injections (53%) if they were more
      effective than eye drops, whereas only 47% would accept a ring; fewer would
      accept any device if it were equally or less effective than drops. Participants
      were also 36% (95% confidence interval=0.44-0.92; P=0.02) less likely to accept
      rings and 32% (95% confidence interval=0.47-0.98; P=0.04) less likely to accept
      subconjunctival injections as compared with contacts. CONCLUSION: Most glaucoma
      patients considered sustained drug-delivery modalities acceptable alternatives to
      IOP-lowering eye drops, but only when they were said to obviate surgery or
      demonstrate greater efficacy than eye drops.

PMID- 29462014
TI  - Surgical Outcome of Replacing a Failed Ahmed Glaucoma Valve by a Baerveldt
      Glaucoma Implant in the Same Quadrant in Refractory Glaucoma.
AB  - PURPOSE: The purpose of this study was to describe the surgical technique and
      outcomes in eyes that underwent surgery to replace a failed Ahmed valve by a
      Baerveldt glaucoma implant in the same quadrant. METHODS: This study was a
      retrospective case series of 9 patients. Parameters analyzed include age,
      glaucoma type, prior surgery, complications, intraocular pressure (IOP), visual
      acuity, and number of glaucoma medications before and after the surgery. Surgical
      success was defined as having either an IOP below 21 mm Hg or a 20% IOP
      reduction, with or without hypotensive agent. RESULTS: The mean follow-up
      duration was 47 months. After surgery, at the time of final follow-up, the mean
      IOP decreased from 29.9 mm Hg to 16.7 mm Hg (36% of mean IOP reduction; P=0.008).
      There was a significant reduction of hypotensive agents from a mean of 4.33 to
      2.22 (P=0.02). The visual acuity did not have a significant deterioration
      (P=0.07). In the final visit, 5 of 9 patients met total success criteria and 2
      patients were qualified successes. Two cases failed totally after 69 and 125
      months of follow-up. The cumulative probability of total success after 6 months
      was 76% and this rate remained stable until the sixth year. One patient had
      bullous keratopathy. Two patients had early postoperative pressure spikes: the
      first patient was treated by trabeculectomy, and the second by vitrectomy.
      CONCLUSIONS: A replacement of the failed Ahmed glaucoma valve by a new Baerveldt
      glaucoma implant in the same quadrant can be a reasonable choice to control
      refractory glaucoma.

PMID- 29462016
TI  - Diurnal Variations of Peripapillary and Macular Vessel Density in Glaucomatous
      Eyes Using Optical Coherence Tomography Angiography.
AB  - PURPOSE: The purpose of this study was to investigate the diurnal variation in
      peripapillary and macular vessel density (VD) measurements using optical
      coherence tomographic angiography (OCT-A) and its correlation to intraocular
      pressure (IOP) changes in glaucoma patients. METHODS: Prospective, observational
      cross-sectional study including 37 patients (74 eyes; age, 63.8+/-12.9 y) with
      open-angle glaucoma. OCT-A imaging and IOP measurements were performed at 08:00,
      11:00, 14:00, and 16:00 timepoints on a single day. At each timepoint, 2 scan
      protocols were used to generate 3-dimensional en face OCT angiograms: 4.5*4.5-mm
      scan centered on the optic nerve head and 6*6-mm scan centered on the fovea. For
      each scan mode, the "radial peripapillary capillary" segment, composed of the
      vasculature of the retinal nerve fiber layer and ganglion cell layer, was
      calculated. Two trained readers reviewed OCT-A image quality. Only scans with
      signal strength intensity (SSI) higher than 46 and without image artifacts
      interfering with measurements were included. Variation in VD measurements
      assessed using analysis of variance (ANOVA) and the association between VD and
      IOP changes assessed using linear mixed modeling methods. RESULTS: The optic
      nerve head and peripapillary VD measurements at 14:00 and 16:00 timepoints were
      greater than the measurements at 08:00 and 11:00 timepoints. The 14:00 and 16:00
      VD measurements were statistically significantly greater (P<0.05) than the 08:00
      measurements for the whole en face (50.1% and 50.1% vs. 49.4%), inside disc
      (50.6% and 50.5% vs. 49.6%), and average peripapillary (58.2% and 58.5% vs.
      57.5%) VDs. The macular VD measurements at the 14:00 timepoint were greater than
      the measurements at 08:00 and 11:00 timepoints. Changes in VD were significantly
      associated with changes in SSI but not IOP. CONCLUSIONS: Diurnal changes in OCT-A
      measured VD in glaucoma patients were small and clinically insignificant. These
      changes were not associated with IOP changes.

PMID- 29462015
TI  - Macular Vessel Density in Glaucomatous Eyes With Focal Lamina Cribrosa Defects.
AB  - PURPOSE: To compare optical coherence tomography angiography (OCTA) measured
      macular vessel density and spectral domain optical coherence tomography (SDOCT)
      measured macular ganglion cell complex (GCC) thickness in primary open-angle
      glaucoma eyes with and without focal lamina cribrosa (LC) defects. METHODS: In
      this cross-sectional, case-control study of patients with primary open-angle
      glaucoma, 46 eyes of 46 patients with LC defects and 54 eyes of 54 patients
      without observable LC defects were included. OCTA and SDOCT imaging were
      performed on the same day by the same operator. Perimetry and swept-source OCT
      testing used to identify LC defects were conducted within 6 months of OCTA and
      SDOCT testing. Global and local parafoveal vessel density and macular GCC
      thickness were compared between study groups. RESULTS: Glaucoma severity was
      similar between groups (SAP mean deviation=-5.63 and -4.64 dB for eyes with and
      without LC defects, respectively; P=0.40). Global and local measured parafoveal
      vessel density was similar between groups (all P>=0.11). GCC focal loss volume
      was higher in eyes with LC defects than eyes without LC defects (7.2% and 4.97%,
      respectively; P=0.03). In addition, GCC focal loss volume was topographically
      related to defect location in LC defect eyes. CONCLUSIONS: Although OCTA macular
      vessel density was not significantly different between eyes with and without LC
      defects, focal GCC loss in eyes with LC defects was different. This highlights
      the importance of not relying solely on vessel density measurements for
      determining macular changes for diagnosing and detecting glaucomatous
      progression.

PMID- 29462017
TI  - Suzanne Noel: Dermatologic Surgeon and Cosmetic Surgery Pioneer.

PMID- 29462018
TI  - A Novel, Multidisciplinary Approach in the Treatment of Perianal Paget Disease.

PMID- 29462020
TI  - Pubic Hair Restorative Surgery Using Grafts Harvested by the Nonshaven Follicular
      Unit Extraction Technique.
AB  - BACKGROUND: Pubic atrichosis or hypotrichosis is quite common among Korean women.
      Although Korean people are increasingly opening up to Western culture, pubic hair
      transplantation is still pursued for cultural reasons. However, many hesitate to
      undergo restorative surgery because follicular unit strip surgery would leave a
      linear donor scar, preventing patients from hiding their surgical history. Thus,
      follicle harvesting using nonshaven follicular unit extraction (NS-FUE), aside
      from many other strengths, is very useful when performing pubic restorative
      surgery. There has been no previous report concerning the effectiveness of NS-FUE
      for treating pubic atrichosis or hypotrichosis. OBJECTIVE: To investigate the
      effectiveness of NS-FUE when performing pubic restorative surgery. MATERIALS AND
      METHODS: The 50 patients who were included in the study underwent pubic hair
      restoration using NS-FUE between March 2014 and June 2016 at Dana Plastic Surgery
      Clinic (Seoul, Korea), and were followed for at least 10 months afterward.
      Patients and the surgeon completed a survey about donor and recipient site
      surgical results using a 5-point Likert scale. RESULTS: The average satisfaction
      scores of patients and surgeon were 4.5 and 4.6, respectively. CONCLUSION:
      Nonshaven follicular unit extraction is one of the most effective harvesting
      methods when performing restorative surgery for patients with pubic atrichosis or
      hypotrichosis.

PMID- 29462019
TI  - Clinico-Surgical Characteristics of Head and Neck Lipomas.

PMID- 29462012
TI  - Neuroinflammation and Central Sensitization in Chronic and Widespread Pain.
AB  - Chronic pain is maintained in part by central sensitization, a phenomenon of
      synaptic plasticity, and increased neuronal responsiveness in central pain
      pathways after painful insults. Accumulating evidence suggests that central
      sensitization is also driven by neuroinflammation in the peripheral and central
      nervous system. A characteristic feature of neuroinflammation is the activation
      of glial cells, such as microglia and astrocytes, in the spinal cord and brain,
      leading to the release of proinflammatory cytokines and chemokines. Recent
      studies suggest that central cytokines and chemokines are powerful
      neuromodulators and play a sufficient role in inducing hyperalgesia and allodynia
      after central nervous system administration. Sustained increase of cytokines and
      chemokines in the central nervous system also promotes chronic widespread pain
      that affects multiple body sites. Thus, neuroinflammation drives widespread
      chronic pain via central sensitization. We also discuss sex-dependent
      glial/immune signaling in chronic pain and new therapeutic approaches that
      control neuroinflammation for the resolution of chronic pain.

PMID- 29462021
TI  - Review of Endovenous Thermal Ablation of the Great Saphenous Vein: Endovenous
      Laser Therapy Versus Radiofrequency Ablation.
AB  - BACKGROUND: Endovenous thermal ablation is a popular treatment for varicose veins
      of the greater saphenous vein. Two common techniques of thermal ablation are
      endovenous laser therapy (EVLT) and radiofrequency ablation (RFA). OBJECTIVE: The
      authors compare EVLT and RFA in vein therapy. METHODS: A review was conducted
      using PubMed. Studies comparing the treatment modalities were gathered and
      compared on the basis of 5 main standpoints, including: efficacy, side effects,
      serious complications, recurrence, and quality of life. RESULTS: It was found
      that EVLT and RFA are both highly efficacious (>80%). Endovenous laser therapy
      seems to be slightly more efficacious than RFA in numerous studies but its
      significance is uncertain. Side effect profiles varied regarding postoperative
      pain and bruising because both were seen to be significantly less using RFA.
      Serious complications were found to be rare in both with no significant
      difference in incidence. Recanalization rate was observed to be higher using RFA
      with uncertainty in significance among various studies. Quality of life improved
      after both procedures with no significant difference among the 2. CONCLUSION:
      Efficacy and recurrence rate seem to favor EVLT, whereas postoperative pain and
      bruising favor RFA. Further studies are needed to validate the significance of
      the differences found.

PMID- 29462022
TI  - 3D Modeling and Mohs Surgery: A Novel Approach to Medical and Patient Education.

PMID- 29462023
TI  - Advocating the Development of Next-Generation High-Relaxivity Gadolinium Chelates
      for Clinical Magnetic Resonance.
AB  - The question of improved relaxivity, and potential efficacy therein, for a next
      generation of magnetic resonance gadolinium chelates with extracellular
      distribution and renal excretion, which could also be viewed from the perspective
      of dose, is addressed on the basis of historical development, animal
      experimentation, and human trials. There was no systematic evaluation that
      preceded the choice of 0.1 mmol/kg as the standard dose for human imaging with
      the gadolinium chelates. In part, this dose was chosen owing to bloodwork
      abnormalities seen in phase I and phase II studies. Animal investigations and
      early clinical trials demonstrated improved lesion detectability at higher doses
      in the brain, liver, and heart. By designing an agent with substantially improved
      relaxivity, higher enhancement equivalent to that provided with the conventional
      gadolinium agents at high dose could be achieved, translating to improved
      diagnosis and, thus, clinical care. Implicit in the development of such high
      relaxivity agents would be stability equivalent to or exceeding that of the
      currently approved macrocyclic agents, given current concern regarding
      dechelation and gadolinium deposition in the brain, skin, and bone with the
      linear agents that were initially approved. Development of such next-generation
      agents with a substantial improvement in relaxivity, in comparison with the
      current group of approved agents, with a 2-fold increase likely achievable, could
      lead to improved lesion enhancement, characterization, diagnosis, and, thus,
      clinical efficacy.

PMID- 29462024
TI  - Characterization of Small Renal Tumors With Magnetic Resonance Elastography: A
      Feasibility Study.
AB  - OBJECTIVES: The aim of this study was to explore the feasibility of magnetic
      resonance elastography (MRE) for characterizing indeterminate small renal tumors
      (SRTs) as part of a multiparametric magnetic resonance (MR) imaging protocol.
      MATERIALS AND METHODS: After institutional review board approval and informed
      consent were obtained, 21 prospective adults (15 men; median age, 55 years; age
      range, 25-72 years) with SRT were enrolled. Tumors (2-5 cm O) were imaged using 3
      directional, gradient echo MRE. Viscoelastic parametric maps (shear wave velocity
      [c] and attenuation [alpha]) were analyzed by 2 independent radiologists.
      Interobserver agreement (Bland-Altman statistics and intraclass correlation
      coefficients) was assessed. Anatomical T2-weighted, dynamic contrast-enhanced
      (DCE) and diffusion sequences completed the acquisition protocol. Imaging
      parameters were compared between groups (Mann-Whitney U test). RESULTS: Quality
      of MRE was good in 18 cases (mean nonlinearity <50%), including 1 papillary renal
      cell carcinoma and 1 metanephric adenoma. A cohort of 5 oncocytomas and 11 clear
      cell renal cell carcinomas (ccRCCs) was analyzed for statistical differences. The
      MRE viscoelastic parameters were the strongest imaging discriminators:
      oncocytomas displayed significantly lower shear velocity c (median, 0.77 m/s;
      interquartile range [IQR], 0.76-0.79) (P = 0.007) and higher shear attenuation
      alpha (median, 0.087 mm; IQR, 0.082-0.087) (P = 0.008) than ccRCC (medians, 0.92
      m/s and 0.066 mm; IQR, 0.84-0.97 and 0.054-0.074, respectively). T2 signal
      intensity ratio (tumor/renal cortex) was lower in oncocytomas (P = 0.02). The DCE
      and diffusion MR parameters overlapped substantially (P >= 0.1). Oncocytomas
      displayed a consistent MRE viscoelastic profile, corresponding to data point
      clustering in a bidimensional scatter plot. Values for MRE intraclass correlation
      coefficient were 0.982 for c and 0.984 for alpha, indicating excellent
      interobserver agreement. CONCLUSIONS: Magnetic resonance elastography is feasible
      for SRT characterization; MRE viscoelastic parameters were stronger
      discriminators between oncocytoma and ccRCC than anatomical, DCE and diffusion MR
      imaging parameters.

PMID- 29462025
TI  - Primary biliary cholangitis is more severe in previous hepatitis B virus
      infection patients.
AB  - OBJECTIVES: The aim of this study was to evaluate the association between
      previous hepatitis B virus (HBV) infection and the severity of primary biliary
      cholangitis (PBC). PATIENTS AND METHODS: A total of 379 HBsAg-negative PBC
      patients were investigated between 2012 and 2017 in this study. Fifty-two of
      these patients underwent liver biopsy. The enrolled patients were divided into an
      anti-HBc-positive group and an anti-HBc-negative group; the patients with liver
      biopsy were further divided into early stage (stage I) and advanced stage (stages
      II, III, and IV) according to histological assessment. Liver fibrosis was also
      assessed by noninvasive prognosis scores including the Mayo Risk Score, the
      Newcastle model, the aspartate aminotransferase-to-platelet ratio index, the
      fibrosis index based on the four factors (FIB-4), and the albumin-bilirubin
      score. The difference in disease stage between the two groups was assessed by
      histological stage and noninvasive scores predicting fibrosis. RESULTS: The
      histology showed that more patients in the anti-HBc-positive group had advanced
      stage compared with anti-HBc-negative patients (P<0.05). Higher Mayo Risk Score,
      the Newcastle model, aminotransferase-to-platelet ratio index, and fibrosis index
      based on the four factors (all P<0.05) were obtained in all patients except for
      the albumin-bilirubin score (P=0.096). CONCLUSION: Previous HBV infection was
      associated with a worse histological stage and advanced fibrosis score of PBC. It
      appears that the previous HBV infection may have aggravated the PBC severity,
      potentially leading to poorer outcomes.

PMID- 29462026
TI  - Anticoagulant therapy for venous thromboembolism in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: There is lack of evidence to guide the type, intensity, and the
      duration of anticoagulation following venous thromboembolism (VTE) in patients
      with inflammatory bowel disease (IBD). PATIENTS AND METHODS: Registro
      Informatizado Enfermedad Trombo Embolica (RIETE) is an ongoing, multicenter,
      observational registry of consecutive patients with symptomatic, objectively
      confirmed, acute VTE. We used the RIETE database to compare the rate of VTE
      recurrences and major bleeding during the course of anticoagulation in noncancer
      patients with or without IBD. RESULTS: As of October 2014, 41 927 patients
      without active cancer have been recruited in RIETE. Of these, 265 (0.63%) had IBD
      and 85 (32%) had the VTE during an acute flare. The duration of anticoagulation
      was similar in patients with VTE during an acute flare (8.3+/-8.8 months), in
      remission (9.4+/-11.5 months), or without IBD (10.0+/-12.8 months). The rate of
      VTE recurrences [7.25, 95% confidence interval (CI): 1.46-21.2; 8.84, 95% CI:
      3.23-19.2; and 5.85, 95% CI: 5.46-6.26 per 100 patient-years, respectively] and
      major bleeding (7.25, 95% CI: 1.46-21.2; 2.95, 95% CI: 0.33-10.6; and 4.79, 95%
      CI: 4.44-5.15, respectively) were similar in all three subgroups. Propensity
      score matching analysis confirmed the absence of differences in the rate of VTE
      recurrences (rate ratio: 1.16, 95% CI: 0.54-2.47) or major bleeding (rate ratio:
      0.84, 95% CI: 0.31-2.23) between patients with or without IBD. CONCLUSION:
      Therapeutic anticoagulation for patients with IBD and VTE is as safe and
      effective as for those with VTE without IBD.

PMID- 29462027
TI  - Transjugular intrahepatic portosystemic shunt creation for cirrhotic portal
      hypertension is well tolerated among patients with portal vein thrombosis.
AB  - BACKGROUND: Portal vein thrombosis (PVT) develops in cirrhotic patients because
      of stagnation of blood flow. Transjugular intrahepatic portosystemic shunt (TIPS)
      creates a low-resistance conduit that restores portal venous patency and blood
      flow. AIM: The effect of PVT on transplant-free survival in cirrhotic patients
      undergoing TIPS creation was evaluated. PATIENTS AND METHODS: A multicenter,
      retrospective cohort study of patients who underwent TIPS creation for cirrhotic
      portal hypertension was carried out. A Cox model with propensity score adjustment
      was developed to evaluate the effect of PVT on 90-day and 3-year transplant-free
      survival. A subgroup analysis examining mortality of those with superior and
      inferior PVT was also carried out. RESULTS: A total of 252 consecutive TIPS
      creations were assessed, including 65 in patients with PVT. Survival of patients
      with high Model for End-stage Liver Disease scores (>=18) and PVT was not
      statistically different compared with patients with low Model for End-stage Liver
      Disease scores (<18) and no PVT at 90 days (P=0.46) and 3 years (P=0.42). Those
      with superior PVT had improved 90-day and 3-year survival both compared with
      patients with a inferior PVT and those without a PVT (P<0.01, all cases).
      CONCLUSION: The presence of PVT does not impair the prognosis of patients
      following TIPS creation, particularly in patients with superior portal occlusion.

PMID- 29462028
TI  - The operative risk and natural history after the diagnosis of ileal penetrating
      Crohn's disease.
AB  - BACKGROUND AND PURPOSE: Crohn's disease (CD) is marked by transmural inflammation
      of the bowel wall leading to stricturing and/or penetrating complications in the
      majority of patients. The natural history and operative risk after the diagnosis
      of an ileal penetrating complication is understudied. The aim was to study the
      disease course and need for surgery in patients diagnosed with a penetrating
      ileal CD complication and to assess the risk factors associated with worse
      postoperative outcome. PATIENTS AND METHODS: In this cohort study, all cross
      sectional imaging exams (computed tomography and/or magnetic resonance imaging)
      performed between 2006 and 2014 in patients with CD in a tertiary referral centre
      were reviewed for the presence of ileal penetrating complications (defined as
      abscesses, phlegmones and/or fistula). Demographic, clinical, biochemical,
      radiological and endoscopic factors were assessed retrospectively in these
      patients as well as the need for surgery (intestinal resection and/or
      strictureplasties) and postoperative complications. RESULTS: In total, 1803 cross
      sectional imaging exams in 957 CD patients were performed during the study
      period. In 113 patients, penetrating ileal CD complications were identified. The
      majority of these patients were referred for surgery (86%) (median time to
      surgery 1 month, interquartile range: 1-4.9 months). In multivariate analysis,
      only the presence of abscesses was associated with subsequent surgery (P=0.034;
      hazard ratio=1.65; 95% confidence interval: 1.04-2.61). Severe postoperative
      complications (Dindo-Clavien>II) were present in 13% of the patients. Albumin
      less than 32 g/l was associated with a five-fold increase in severe complications
      (P=0.039; hazard ratio=4.9; 95% confidence interval: 1-22). Up to 35% of the
      patients needed no further medical treatment during the first 5 years
      postoperatively. CONCLUSION: In this cohort, the majority of patients with
      penetrating ileal CD underwent surgery. The presence of an abscess showed a
      significant association with the need for surgery. There was an acceptable
      postoperative complication rate. Patients with low albumin had an unfavourable
      postoperative course. The long-term outcome after surgery was favourable.

PMID- 29462030
TI  - Refining Risk Adjustment for the Proposed CMS Surgical Hip and Femur Fracture
      Treatment Bundled Payment Program.
AB  - BACKGROUND: The U.S. Centers for Medicare & Medicaid Services (CMS) has been
      considering the implementation of a mandatory bundled payment program, the
      Surgical Hip and Femur Fracture Treatment (SHFFT) model. However, bundled
      payments without appropriate risk adjustment may be inequitable to providers and
      may restrict access to care for certain patients. The SHFFT proposal includes
      adjustment using the Diagnosis-Related Group (DRG) and geographic location. The
      goal of the current study was to identify and quantify patient factors that could
      improve risk adjustment for SHFFT bundled payments. METHODS: We retrospectively
      reviewed a 5% random sample of Medicare data from 2008 to 2012. A total of 27,898
      patients were identified who met SHFFT inclusion criteria (DRG 480, 481, and
      482). Reimbursement was determined for each patient over the bundle period (the
      surgical hospitalization and 90 days of post-discharge care). Multivariable
      regression was performed to test demographic factors, comorbidities, geographic
      location, and specific surgical procedures for associations with reimbursement.
      RESULTS: The average reimbursement was $23,632 +/- $17,587. On average,
      reimbursements for male patients were $1,213 higher than for female patients (p <
      0.01). Younger age was also associated with higher payments; e.g., reimbursement
      for those >=85 years of age averaged $2,282 +/- $389 less than for those aged 65
      to 69 (p < 0.01). Most comorbidities were associated with higher reimbursement,
      but dementia was associated with lower payments, by an average of $2,354 +/- $243
      (p < 0.01). Twenty-two procedure codes are included in the bundle, and patients
      with the 3 most common codes accounted for 98% of the cases, with average
      reimbursement ranging from $22,527 to $24,033. Less common procedures varied by
      >$20,000 in average reimbursement (p < 0.01). DRGs also showed significant
      differences in reimbursement (p < 0.01); e.g., DRG 480 was reimbursed by an
      average of $10,421 +/- $543 more than DRG 482. Payments varied significantly by
      state (p <= 0.01). Risk adjustment incorporating specific comorbidities
      demonstrated better performance than with use of DRG alone (r = 0.22 versus
      0.15). CONCLUSIONS: Our results suggest that the proposed SHFFT bundled payment
      model should use more robust risk-adjustment methods to ensure that providers are
      reimbursed fairly and that patients retain access to care. At a minimum, payments
      should be adjusted for age, comorbidities, demographic factors, geographic
      location, and surgical procedure.

PMID- 29462029
TI  - Patient tolerance and acceptance of different colonic imaging modalities: an
      observational cohort study.
AB  - BACKGROUND: Less invasive alternatives to optical colonoscopy (OC) may improve
      patient compliance with investigation, but study of patient preference is
      limited. OBJECTIVES: The aims of this study were to determine patient tolerance
      and acceptability of OC, computed tomography colonography (CTC) and colon capsule
      endoscopy (CCE) and also to determine the choice of investigation made by fully
      informed members of the lay public. PATIENTS AND METHODS: Patients assigned a
      Gloucester Comfort Score (GCS, 1-5; as did endoscopists), an overall test
      experience score (visual analogue scale, 0-10) and completed a 'Friends and
      Family Test' following OC, CTC or CCE. In the second part of the study, members
      of the public were given information detailing the nature, tolerance,
      acceptability, risks and outcomes and invited to choose which test they would
      prefer in the event that one was needed. RESULTS: Assessed by endoscopist and
      patient, respectively, 24.2 and 49.3% (P<0.005) of symptomatic and 27.3 and 22.1%
      (P=0.4) of Bowel Cancer Screening Programme patients suffered moderate to severe
      discomfort (GCS: 4-5) [GCS (mean+/-SEM): 3.32+/-0.085, 1.96+/-0.083 and 1.30+/
      0.088 (P<0.001); overall experience: 5.43, 2.35 and 3.80 (P<0.001)]. In all,
      93.6, 96.1 and 85.7% of OC, CTC and CCE patients, respectively, were willing to
      undergo the same test under the same circumstances. The lay public (n=100) chose
      a noninvasive test (CTC or CCE) in 55% of the cases to investigate symptoms and
      chose a Bowel Cancer Screening Programme test in 29% of the cases (P<0.001).
      CONCLUSION: Patient tolerance and experience favours CTC and CCE over OC and
      informed about all aspects of each procedure; a noninvasive option is commonly
      chosen by the lay public.

PMID- 29462031
TI  - Minimum Two-Year Follow-up of Anterior Cruciate Ligament Reconstruction in
      Patients with Generalized Joint Laxity.
AB  - BACKGROUND: The purposes of this investigation were to compare outcomes of
      anterior cruciate ligament (ACL) reconstruction between patients with generalized
      joint laxity and those without it and to investigate the effect of generalized
      joint laxity on outcomes of ACL reconstruction from 2 to 8 years postoperatively.
      METHODS: We retrospectively reviewed 163 patients who had undergone unilateral
      ACL reconstruction from January 2001 to December 2008. Patients were divided into
      2 groups according to presence or absence of generalized joint laxity. The
      proportions of patients with meniscectomy, graft rupture, and contralateral ACL
      rupture were compared. Rupture rates were compared with Kaplan-Meier analysis.
      The Lachman test, pivot-shift test, and anterior translation measured with the KT
      2000 arthrometer were evaluated. The Lysholm knee score and International Knee
      Documentation Committee (IKDC) subjective score were compared. The IKDC objective
      grade and radiographic grade were also evaluated. Follow-up assessments were
      performed at 2, 5, and 8 years postoperatively. RESULTS: The proportions of
      meniscectomy, graft rupture, and contralateral ACL rupture in patients with
      generalized joint laxity were higher than in patients without generalized joint
      laxity during the whole evaluation period. However, differences in proportions
      and cumulative rupture rates did not reach significance (p > 0.05). Patients with
      generalized joint laxity had less stability and poorer functional outcomes at the
      8-year follow-up compared with patients without generalized joint laxity. With
      regard to the Lachman test and anterior translation, poorer results were shown in
      patients with generalized joint laxity than in patients without generalized joint
      laxity during the whole evaluation period. The results of pivot-shift testing
      differed significantly at 5 years (p = 0.002) and 8 years (p = 0.007). Patients
      with generalized joint laxity also had worse Lysholm knee scores and IKDC
      subjective scores during the whole evaluation period; these differences may not
      be clinically important. Comparisons between serial outcomes measured at 2, 5,
      and 8-year follow-ups within each patient group showed that anterior translation
      (p = 0.002), Lysholm knee score (p = 0.014), and IKDC subjective score (p =
      0.002) deteriorated over time, although the values at 8 years were similar to
      those at 5 years, in patients with generalized joint laxity. CONCLUSIONS:
      Generalized joint laxity as an inherent physiologic characteristic of patients
      was related to a significant adverse effect on stability and functional outcomes
      of ACL reconstruction for patients followed for 2 to 8 years. Generalized joint
      laxity should be considered a risk factor for poor outcomes after ACL
      reconstruction. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 29462032
TI  - Perioperative Allogeneic Red Blood-Cell Transfusion Associated with Surgical Site
      Infection After Total Hip and Knee Arthroplasty.
AB  - BACKGROUND: Perioperative allogeneic red blood-cell transfusion is a suspected
      risk factor for surgical site infection (SSI) after total joint arthroplasty
      (TJA), but the interrelationships among SSI risk, transfusion dose, preoperative
      anemia, and the presence of coagulopathies have not been well described. METHODS:
      Data on SSI within 1 year after surgery as well as on transfusion with blood
      products within 30 days after surgery were obtained for 6,788 patients who had
      undergone primary or revision total hip or knee arthroplasty from 2000 to 2011 in
      a single hospital system. Multivariate logistic regression modeling was used to
      determine the independent association between allogeneic red blood-cell
      transfusion and SSI. RESULTS: There was a dose-dependent association between
      allogeneic red blood-cell transfusion and SSI, with the infection rate increasing
      as the transfusion dose increased from 1 unit (odds ratio [OR] = 1.97; 95%
      confidence interval [CI] = 1.38, 2.79; p < 0.001), to 2 units (OR = 2.20; CI =
      1.37, 3.44; p = 0.002), to 3 units (OR = 3.66; CI = 1.72, 7.16; p = 0.001), and
      to >3 units (OR = 7.40; CI = 4.91, 11.03; p < 0.001) after controlling for
      medical comorbidities, planned procedure, preoperative anemia, and preexisting
      coagulopathies. A preexisting bleeding disorder (OR = 2.09; CI = 1.57, 2.80; p <
      0.001) and clotting disorder (OR = 1.37; CI = 1.14, 1.64; p = 0.001) and
      preoperative anemia (OR = 3.90; CI = 3.31, 4.61; p < 0.001) were all independent
      risk factors for transfusion after adjusting for the planned procedure.
      CONCLUSIONS: We found a dose-dependent relationship between allogeneic red blood
      cell transfusion and SSI risk after total hip or knee arthroplasty. Additionally,
      preoperative anemia or a known bleeding or clotting disorder were risk factors
      for the need for allogeneic red blood-cell transfusion. Our findings underscore
      the need for preoperative risk assessment, methods to limit surgical tissue
      injury, and optimized blood conservation strategies. LEVEL OF EVIDENCE:
      Therapeutic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 29462033
TI  - Low-Dose Epinephrine Plus Tranexamic Acid Reduces Early Postoperative Blood Loss
      and Inflammatory Response: A Randomized Controlled Trial.
AB  - BACKGROUND: The reductions of perioperative blood loss and inflammatory response
      are important in total knee arthroplasty. Tranexamic acid reduced blood loss and
      the inflammatory response in several studies. However, the effect of epinephrine
      administration plus tranexamic acid has not been intensively investigated, to our
      knowledge. In this study, we evaluated whether the combined administration of low
      dose epinephrine plus tranexamic acid reduced perioperative blood loss or
      inflammatory response further compared with tranexamic acid alone. METHODS: This
      randomized placebo-controlled trial consisted of 179 consecutive patients who
      underwent primary total knee arthroplasty. Patients were randomized into 3
      interventions: Group IV received intravenous low-dose epinephrine plus tranexamic
      acid, Group TP received topical diluted epinephrine plus tranexamic acid, and
      Group CT received tranexamic acid alone. The primary outcome was perioperative
      blood loss on postoperative day 1. Secondary outcomes included perioperative
      blood loss on postoperative day 3, coagulation and fibrinolysis parameters
      (measured by thromboelastography), inflammatory cytokine levels, transfusion
      values (rate and volume), thromboembolic complications, length of hospital stay,
      wound score, range of motion, and Hospital for Special Surgery (HSS) score.
      RESULTS: The mean calculated total blood loss (and standard deviation) in Group
      IV was 348.1 +/- 158.2 mL on postoperative day 1 and 458.0 +/- 183.4 mL on
      postoperative day 3, which were significantly reduced (p < 0.05) compared with
      Group TP at 420.5 +/- 188.4 mL on postoperative day 1 and 531.1 +/- 231.4 mL on
      postoperative day 3 and Group CT at 520.4 +/- 228.4 mL on postoperative day 1 and
      633.7 +/- 237.3 mL on postoperative day 3. Intravenous low-dose epinephrine
      exhibited a net anti-inflammatory activity in total knee arthroplasty and did not
      induce an obvious hypercoagulable status. Transfusion values were significantly
      reduced (p < 0.05) in Group IV, but no significant differences were observed in
      the incidence of thromboembolic complications, wound score, range of motion, and
      HSS score among the 3 groups (p > 0.05). CONCLUSIONS: The combined administration
      of low-dose epinephrine and tranexamic acid demonstrated an increased effect in
      reducing perioperative blood loss and the inflammatory response compared with
      tranexamic acid alone, with no apparent increased incidence of thromboembolic and
      other complications. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 29462034
TI  - Acute Thoracolumbar Spinal Cord Injury: Relationship of Cord Compression to
      Neurological Outcome.
AB  - BACKGROUND: Spinal cord injury in the cervical spine is commonly accompanied by
      cord compression and urgent surgical decompression may improve neurological
      recovery. However, the extent of spinal cord compression and its relationship to
      neurological recovery following traumatic thoracolumbar spinal cord injury is
      unclear. The purpose of this study was to quantify maximum cord compression
      following thoracolumbar spinal cord injury and to assess the relationship among
      cord compression, cord swelling, and eventual clinical outcome. METHODS: The
      medical records of patients who were 15 to 70 years of age, were admitted with a
      traumatic thoracolumbar spinal cord injury (T1 to L1), and underwent a spinal
      surgical procedure were examined. Patients with penetrating injuries and
      multitrauma were excluded. Maximal osseous canal compromise and maximal spinal
      cord compression were measured on preoperative mid-sagittal computed tomography
      (CT) scans and T2-weighted magnetic resonance imaging (MRI) by observers blinded
      to patient outcome. The American Spinal Injury Association (ASIA) Impairment
      Scale (AIS) grades from acute hospital admission (<=24 hours of injury) and
      rehabilitation discharge were used to measure clinical outcome. Relationships
      among spinal cord compression, canal compromise, and initial and final AIS grades
      were assessed via univariate and multivariate analyses. RESULTS: Fifty-three
      patients with thoracolumbar spinal cord injury were included in this study. The
      overall mean maximal spinal cord compression (and standard deviation) was 40% +/-
      21%. There was a significant relationship between median spinal cord compression
      and final AIS grade, with grade-A patients (complete injury) exhibiting greater
      compression than grade-C and D patients (incomplete injury) (p < 0.05).
      Multivariate logistic regression identified mean spinal cord compression as
      independently influencing the likelihood of complete spinal cord injury (p <
      0.01). CONCLUSIONS: Traumatic thoracolumbar spinal cord injury is commonly
      accompanied by substantial cord compression. Greater cord compression is
      associated with an increased likelihood of severe neurological deficits (complete
      injury) following thoracolumbar spinal cord injury. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 29462035
TI  - Conventional Primary Central Chondrosarcoma of the Pelvis: Prognostic Factors and
      Outcome of Surgical Treatment in 162 Patients.
AB  - BACKGROUND: Studies focusing on the oncological outcome after treatment of
      conventional primary central chondrosarcoma of pelvic bone are lacking. We
      conducted this retrospective study at 5 referral centers to gain insight in the
      outcome of treatment for this tumor type and to identify risk factors for
      impaired oncological outcome. METHODS: One hundred and sixty-two consecutive
      patients (118 male patients [73%]) who underwent resection of a conventional
      primary central chondrosarcoma of pelvic bone from 1985 to 2013 were evaluated.
      The median age was 51 years (range, 15 to 78 years). The median follow-up was
      12.6 years (95% confidence interval [CI], 8.4 to 16.9 years). There were 30 grade
      I lesions (19%), 93 grade-II lesions (57%), and 39 grade-III lesions (24%).
      RESULTS: Sixty-two patients (38%) experienced local recurrence: 9 grade-I lesions
      (30%), 31 grade-II lesions (33%), and 22 grade-III lesions (56%). Forty-eight
      patients (30%) developed metastases. The risk of disease-related death was 3% for
      grade-I tumors (1 of 30; this patient had a grade-II recurrence and died of
      metastases), 33% (31 of 93) for grade-II tumors, and 54% (21 of 39) for grade-III
      tumors. Identified risk factors for impaired disease-specific survival were tumor
      grade (grade II: hazard ratio [HR], 20.18; p = 0.003; and grade III: HR, 58.94; p
      < 0.001), resection margins (marginal: HR, 3.21; p = 0.001; and intralesional:
      HR, 3.56; p < 0.001), and maximal tumor size (HR, 1.08 per cm; p = 0.026). Deep
      infection (19% [n = 31]) was the predominant complication. CONCLUSIONS: This
      study offers a standard for survival rates for conventional primary central
      chondrosarcoma of the pelvis. The survival for grade-I tumors was excellent. Wide
      resection margins were associated with a significant survival advantage for
      higher-grade tumors. Because of the inability to reliably distinguish low-grade
      and high-grade tumors preoperatively, we conclude that any central pelvic
      chondrosarcoma should be treated with aggressive primary resection with the aim
      of obtaining wide resection margins. There may be aggressive biologic features in
      some tumors for which a surgical procedure alone may not be adequate to improve
      outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 29462036
TI  - The Cost of Joint Replacement: Comparing Two Approaches to Evaluating Costs of
      Total Hip and Knee Arthroplasty.
AB  - BACKGROUND: In an era of mandatory bundled payments for total joint replacement,
      accurate analysis of the cost of procedures is essential for orthopaedic surgeons
      and their institutions to maintain viable practices. The purpose of this study
      was to compare traditional accounting and time-driven activity-based costing
      (TDABC) methods for estimating the total costs of total hip and knee arthroplasty
      care cycles. METHODS: We calculated the overall costs of elective primary total
      hip and total knee replacement care cycles at our academic medical center using
      traditional and TDABC accounting methods. We compared the methods with respect to
      the overall costs of hip and knee replacement and the costs for each major cost
      category. RESULTS: The traditional accounting method resulted in higher cost
      estimates. The total cost per hip replacement was $22,076 (2014 USD) using
      traditional accounting and was $12,957 using TDABC. The total cost per knee
      replacement was $29,488 using traditional accounting and was $16,981 using TDABC.
      With respect to cost categories, estimates using traditional accounting were
      greater for hip and knee replacement, respectively, by $3,432 and $5,486 for
      personnel, by $3,398 and $3,664 for space and equipment, and by $2,289 and $3,357
      for indirect costs. Implants and consumables were derived from the actual
      hospital purchase price; accordingly, both methods produced equivalent results.
      CONCLUSIONS: Substantial cost differences exist between accounting methods. The
      focus of TDABC only on resources used directly by the patient contrasts with the
      allocation of all operating costs, including all indirect costs and unused
      capacity, with traditional accounting. We expect that the true costs of hip and
      knee replacement care cycles are likely somewhere between estimates derived from
      traditional accounting methods and TDABC. TDABC offers patient-level granular
      cost information that better serves in the redesign of care pathways and may lead
      to more strategic resource-allocation decisions to optimize actual operating
      margins.

PMID- 29462037
TI  - The Free-Hand Technique for S2-Alar-Iliac Screw Placement: A Safe and Effective
      Method for Sacropelvic Fixation in Adult Spinal Deformity.
AB  - BACKGROUND: Spinopelvic fixation is an integral part of achieving solid fusion
      across the lumbosacral junction, especially in deformity procedures requiring
      substantial correction or long-segment constructs. Traditional S2-alar-iliac
      (S2AI) screw-placement techniques utilize fluoroscopy, increasing operative time
      and radiation exposure to the patient and surgeon. We describe a novel free-hand
      technique for S2AI screw placement in patients with adult spinal deformity.
      METHODS: We reviewed the records of 45 consecutive patients who underwent
      spinopelvic fixation performed with use of S2AI screws by the senior surgeon and
      various fellows or residents over a 12-month period (2015 to 2016). In each case,
      the S2AI screws were placed utilizing a free-hand technique without fluoroscopic
      or image guidance. Screw position and accuracy were assessed by intraoperative O
      arm imaging and analyzed using 3-dimensional interactive manipulation of computed
      tomography images. RESULTS: A total of 100 screws were placed, 51 by the senior
      surgeon and 49 by trainees. The mean patient age was 57.4 +/- 12.7 years at the
      time of surgery; 37 (82.2%) of the patients were female. Preoperative diagnoses
      included adult idiopathic scoliosis (n = 19), adult degenerative scoliosis (n =
      15), flatback syndrome (n = 2), fixed sagittal imbalance (n = 6), and distal
      junctional kyphosis (n = 3). Five (5%) of the screws were placed with moderate to
      severe cortical breaches, all of which perforated the pelvis posteriorly, with no
      clinically notable neurovascular or visceral complications. The breach rate did
      not differ significantly between the senior surgeon and trainees. CONCLUSIONS:
      The free-hand technique for S2AI screw placement, when performed in a
      standardized manner, was demonstrated to be safe and reliable in constructs
      requiring spinopelvic fixation. The accuracy of screw placement relies on visible
      and palpable anatomic landmarks that obviate the need for intraoperative
      fluoroscopy or image guidance, potentially reducing operative time and radiation
      exposure. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 29462039
TI  - Not Using a Tourniquet During Anterior Ankle Arthroscopy Did Not Affect
      Postoperative Intra-Articular Bleeding or Function at Six Months.

PMID- 29462038
TI  - The Creation and Validation of a Knee Bone Age Atlas Utilizing MRI.
AB  - BACKGROUND: In managing many pediatric knee conditions, an accurate bone age
      assessment may be critical for diagnostic, prognostic, and treatment purposes.
      The aim of this study was to create an atlas of magnetic resonance imaging (MRI)
      studies of the knee spanning the pediatric and adolescent years that would enable
      accurate skeletal age to be assessed, potentially forgoing the need for a left
      hand radiograph. METHODS: We performed a retrospective assessment of 11 to 31
      MRIs from male and female patients of each age from 2 to 19 years. Radiographic
      features specific to the patella, tibia, fibula, and femur were documented with
      respect to their presence or absence. From these data, age and sex "standards"
      were established, allowing the creation on an atlas. A separate cohort of MRIs
      with 2 to 13 patients per age and sex was then used to validate the reliability
      and reproducibility of the atlas. RESULTS: In the creation of the atlas, a total
      of 859 MRIs were reviewed. The patella, tibia, fibula, and femur were noted to
      undergo a reproducible sequence of skeletal ossification. The patella provided
      the best age assessment in early childhood. Features specific to the tibia,
      particularly ossification of the tibial spine and the tibial tubercle, were of
      particular importance in children between the ages of 6 and 12 years. MRI
      features of the fibula and femur served a more important role in age assessment
      later in skeletal maturity. From a separate cohort of 323 MRIs utilized to
      validate the atlas, a strong correlation between chronologic age and bone age was
      shown, as was excellent interobserver and intraobserver reliability. CONCLUSIONS:
      The predictable ossification pattern of the patella, tibia, fibula, and femur
      enables accurate bone age calculations to be made from knee MRIs. When treating
      conditions about the knee that require MRI, obtaining an additional left-hand
      radiograph for bone age may be unnecessary. This information can be used to
      potentially avoid additional radiation exposure, impart cost savings, and lead to
      greater clinic efficiency.

PMID- 29462040
TI  - In Patients with One-Level Lumbar Degenerative Spondylolisthesis, a Posterior
      Approach with Transforaminal Lateral Interbody Fusion Improved Radiographic But
      Not Clinical Outcomes.

PMID- 29462041
TI  - The Two-Incision and Mini-Posterior Approaches for Total Hip Arthroplasty Did Not
      Differ in Terms of Outcomes at More Than Eight Years.

PMID- 29462042
TI  - What's New in Pediatric Orthopaedics.

PMID- 29462043
TI  - Equal Pay for Equal Work: Medicare Procedure Volume and Reimbursement for Male
      and Female Surgeons Performing Total Knee and Total Hip Arthroplasty.
AB  - BACKGROUND: The observed sex gap in physician salary has been the topic of much
      recent debate in the United States, but it has not been well-described among
      orthopaedic surgeons. The objective of this study was to evaluate for sex
      differences in Medicare claim volume and reimbursement among orthopaedic
      surgeons. METHODS: The Medicare Provider Utilization and Payment Public Use File
      was used to compare claim volume and reimbursement between female and male
      orthopaedic surgeons in 2013. Data were extracted for each billing code per
      orthopaedic surgeon in the year 2013 for total claims, surgical claims, total
      knee arthroplasty (TKA) claims, and total hip arthroplasty (THA) claims. RESULTS:
      A total of 20,546 orthopaedic surgeons who treated traditional Medicare patients
      were included in the initial analysis. Claim volume and reimbursement received
      were approximately twofold higher for all claims and more than threefold higher
      for surgical claims for male surgeons when compared with female surgeons (p <
      0.001 for all comparisons). A total of 7,013 and 3,839 surgeons performed >10
      TKAs and THAs, respectively, in 2013 for Medicare patients and were included in
      the subset analyses. Although male surgeons performed a higher mean number of
      TKAs than female surgeons (mean and standard deviation, 37 +/- 33 compared with
      26 +/- 17, respectively, p < 0.001), the claim volume for THAs was similar (29 +/
      22 compared with 24 +/- 13, respectively, p = 0.080). However, there was no
      significant difference in mean reimbursement payments received per surgeon
      between men and women for TKA or THA ($1,135 +/- $228 compared with $1,137 +/-
      $184 for TKA, respectively, p = 0.380; $1,049 +/- $226 compared with $1,043 +/-
      $266 for THA, respectively, p = 0.310). CONCLUSIONS: Female surgeons had a lower
      number of total claims and reimbursements compared with male surgeons. However,
      among surgeons who performed >10 THAs and TKAs, there were no sex differences in
      the mean reimbursement payment per surgeon. CLINICAL RELEVANCE: The number of
      women in orthopaedics is rising, and there is much interest in how their
      productivity and compensation compare with their male counterparts.

PMID- 29462044
TI  - Appropriateness Criteria for Total Knee Arthroplasty: Additional Comments and
      Considerations.
AB  - Appropriateness classification for total knee arthroplasty (TKA) has received
      substantial attention recently, and Katz and colleagues published an Orthopaedic
      Forum on the topic in The Journal of Bone & Joint Surgery in February 2017.
      Classifications of appropriateness are particularly important given the rapid
      rise in use of TKA and a variety of third-party payer approaches designed to
      control health-care costs. We respond to some of the concerns addressed by Katz
      and colleagues, and elaborate on what we believe are some important issues
      related to both older and newer appropriateness criteria for TKA.

PMID- 29462045
TI  - Low-Dose Epinephrine Infusions and Tranexamic Acid During Lower-Extremity Total
      Joint Arthroplasty: Commentary on an article by Wei-Nan Zeng, MD, et al.: "Low
      Dose Epinephrine Plus Tranexamic Acid Reduces Early Postoperative Blood Loss and
      Inflammatory Response. A Randomized Controlled Trial".

PMID- 29462046
TI  - Determining the Cost of Total Hip and Knee Arthroplasty: Commentary on an article
      by John A. Palsis, MD, et al.: "The Cost of Joint Replacement. Comparing Two
      Approaches to Evaluating Costs of Total Hip and Knee Arthroplasty".

PMID- 29462047
TI  - S2-Alar-Iliac Screw Placement: Who Needs Imaging?: Commentary on an article by
      Jamal N. Shillingford, MD, et al.: "The Free-Hand Technique for S2-Alar-Iliac
      Screw Placement. A Safe and Effective Method for Sacropelvic Fixation in Adult
      Spinal Deformity".

PMID- 29462048
TI  - Where Are All the Women?: Commentary on an article by Emma B. Holliday, MD, et
      al.: "Equal Pay for Equal Work. Medicare Procedure Volume and Reimbursement for
      Male and Female Surgeons Performing Total Knee and Total Hip Arthroplasty".

PMID- 29462049
TI  - Suprasternal Transcatheter Aortic Valve Replacement in Patients With Marginal
      Femoral Access.
AB  - OBJECTIVE: Recently, the PARTNER 2A trial reported results of transcatheter
      aortic valve replacement versus surgical aortic valve replacement in 2032
      intermediate-risk patients at 2 years. Two hundred thirty-six patients (24%)
      required an access route other than transfemoral. Compared with transfemoral and
      surgical aortic valve replacement, nontransfemoral transcatheter aortic valve
      replacement was associated with a numerically higher rate of death and disabling
      stroke at 30 days. This underscores the need for a better alternative surgical
      approach for patients with marginal femoral access. We reviewed our multicenter
      experience with minimally invasive suprasternal transcatheter aortic valve
      replacement. METHODS: Consecutive patients with symptomatic severe aortic
      stenosis at high or intermediate risk for surgical aortic valve replacement
      underwent suprasternal transcatheter aortic valve replacement. A commercially
      available transcatheter heart valve was deployed under fluoroscopic guidance
      through the innominate artery or ascending aorta. Using a 3-cm skin incision just
      above the sternal notch, the Aegis Transit System (Aegis Surgical Ltd, Galway,
      Ireland) provided illuminated access to the mediastinum without bone disruption.
      Through a purse-string suture placed in the innominate artery or ascending aorta,
      transcatheter aortic valve replacement proceeded similarly to the direct aortic
      approach. RESULTS: Thirty patients at six medical centers successfully underwent
      suprasternal transcatheter aortic valve replacement. Implanted valves included 2
      CoreValve and 12 Evolut-R (Medtronic, Inc, Minneapolis, MN USA), as well as 10
      SAPIEN 3 and 6 SAPIEN XT (Edwards Lifesciences, Corp, Irvine, CA USA) with sizes
      ranging from 23 to 31 mm. Median procedure time was 90 minutes and median
      hospital stay was 4 days. Postoperatively, new permanent pacemaker (n = 3) was
      the most common Vascular Academic Research Consortium 2 complication.
      CONCLUSIONS: These data demonstrate the early clinical feasibility of
      suprasternal transcatheter aortic valve replacement. Key advantages of this
      approach include direct access to the innominate artery and ascending aorta,
      precise sheath control, and confident arterial closure. Additional experience is
      warranted to confirm these favorable results.

PMID- 29462050
TI  - Acute Heart Failure at the Time of Transcatheter Aortic Valve Replacement Does
      Not Increase Mortality.
AB  - OBJECTIVE: Patients presenting for transcatheter aortic valve replacement are
      often in acute on chronic heart failure, as indicated by elevated N-terminal pro
      B-type natriuretic peptide. Many believe that elevated N-terminal pro-B-type
      natriuretic peptide is an indication to treat medically, reserving surgery until
      the patient is medically optimized. METHODS: A single-center transcatheter aortic
      valve replacement database was queried from December 2015 to November 2016 to
      identify patients undergoing transcatheter aortic valve replacement. Patients
      were divided into two cohorts based on preoperative N-terminal pro-B-type
      natriuretic peptide level. An analysis was then completed to assess outcomes such
      as length of intensive care unit stay, total length of stay, discharge to home,
      major complications, and mortality at 30 days. RESULTS: There were 142 patients
      (median age = 80 years, 44% female) with preoperative N-terminal pro-B-type
      natriuretic peptide data included (range = 106-73,500 pg/mL). The mean Society of
      Thoracic Surgeons predicative risk of mortality was 8%, and 46 patients (32%) had
      N-terminal pro-B-type natriuretic peptide of greater than 3000 pg/mL. N-terminal
      pro-B-type natriuretic peptide of greater than 3000 pg/mL was associated only
      with increased intensive care unit length of stay of greater than 24 hours (35%
      vs 9%, P = 0.0001). There was no statistical difference between cohorts with
      regard to total length of stay of greater than 3 days (24% vs 15%, P = 0.2),
      discharge to home (74% vs 83%, P = 0.3), major complication, or mortality at 30
      days. CONCLUSIONS: Transcatheter aortic valve replacement is an appropriate and
      effective treatment for patients with aortic stenosis presenting with high N
      terminal pro-B-type natriuretic peptide and acute on chronic heart failure.

PMID- 29462051
TI  - Long-Term Outcome of Patients Undergoing Minimally Invasive Direct Coronary
      Artery Bypass Surgery: A Single-Center Experience.
AB  - OBJECTIVE: The primary objective was to investigate the long-term survival of
      patients who underwent single-vessel coronary revascularization with minimally
      invasive direct coronary artery bypass surgery with or without hybrid
      revascularization. The secondary outcome measures were repeat revascularization
      either by coronary artery bypass grafting or by percutaneous coronary
      intervention and the incidence of myocardial infarction or recurrent angina.
      METHODS: This is a retrospective study of prospectively collected data of
      patients who underwent minimally invasive direct coronary artery bypass procedure
      in our center between January 2001 and December 2015. Procedures were performed
      either through small left anterolateral thoracotomy or lower midline sternotomy.
      RESULTS: A total of 182 patients were identified: 100 underwent minimally
      invasive direct coronary artery bypass to the left anterior descending artery and
      82 underwent hybrid revascularization (percutaneous coronary intervention to
      coronary arteries other than the left anterior descending artery along with
      minimally invasive direct coronary artery bypass to the left anterior descending
      artery). The mean +/- SD age was 62 +/- 10.1 years. Preoperatively 82% were male,
      and 72.5% patients had good left ventricular function. The median follow-up
      period was 10.9 years. There was no in-hospital or 30-day mortality. The 10-year
      actuarial survival was 84.8%. Freedom from repeat revascularization was 98.9% at
      1 year and 89.9% at 10 years. At follow-up, freedom from myocardial infarction
      was 96.7% whereas freedom from angina was 92.9%. CONCLUSIONS: Within the
      limitations imposed by retrospective analyses, our study demonstrates excellent
      long-term outcome in patients undergoing minimally invasive direct coronary
      artery bypass with or without hybrid revascularization. For isolated left
      anterior descending artery disease minimally invasive direct coronary artery
      bypass should be considered, whereas hybrid revascularization (percutaneous
      coronary intervention and minimally invasive direct coronary artery bypass)
      should be considered for multivessel disease.

PMID- 29462052
TI  - Does Robotic Beating Heart Connector Totally Endoscopic Coronary Artery Bypass
      Bridge the Gender Gap in Coronary Bypass Surgery?
AB  - OBJECTIVE: Previous studies have shown that women carry a higher risk of
      morbidity and mortality after coronary artery bypass surgery. We investigated
      gender differences in risk factors and outcomes in our patients undergoing
      robotic beating heart connector totally endoscopic coronary artery bypass.
      METHODS: From July 2013 to April 2017, patients undergoing connector totally
      endoscopic coronary artery bypass were reviewed. We compared the outcomes of men
      versus women. RESULTS: A total of 192 men and 71 women underwent connector
      totally endoscopic coronary artery bypass. The mean +/- SD age was 65.4 +/- 10.6
      years. The Society of Thoracic Surgeons score was higher in women than men
      (median = 1.46 vs 0.73, P = 0.001), and women had a higher rate of peripheral
      vascular disease (22.5% vs 9.9%, P = 0.007). Intraoperative data in women and men
      were similar except for the rate of multi-vessel connector totally endoscopic
      coronary artery bypass and the rate of bilateral internal mammary artery use,
      which were both lower in women (49.3% vs 64.6%, P = 0.024, and 42.3% vs 56.8%, P
      = 0.036, respectively). The mean +/- SD length of hospital stay (women vs men:
      3.99 +/- 4.00 vs 3.39 +/- 2.42, P = 0.324) was comparable. The 30-day mortality
      in women and men was 0% (0/71) and 2.1% (4/192), respectively (P = 0.577). The
      morbidity and mortality of single- or multi-vessel connector totally endoscopic
      coronary artery bypass were similar between men and women. CONCLUSIONS: We
      conclude that the morbidity and mortality in women after robotic beating heart
      connector totally endoscopic coronary artery bypass in our center were similar to
      those seen in men.

PMID- 29462053
TI  - Vitamin K antagonists and emergencies.
AB  - The recent emergence of 'non-VKA' oral anticoagulants may have led to some
      forgetting that vitamin K antagonists (VKA) are by far the most widely prescribed
      oral anticoagulants worldwide. Consequently, we decided to summarize the
      information available on them. This paper presents the problems facing emergency
      physicians confronted with patients on VKAs in 10 points, from pharmacological
      data to emergency management. Vitamin K antagonists remain preferable in many
      situations including in the elderly, in patients with extreme body weights,
      severe chronic kidney or liver disease or valvular heart disease, and in patients
      taking VKAs with well-controlled international normalized ratios (INRs). Given
      the way VKAs work, a stable anticoagulant state can only be achieved at the
      earliest 5 days after starting therapy. The induction phase of VKA treatment is
      associated with the highest risk of bleeding; validated algorithms based on INR
      values have to be followed. VKA asymptomatic overdoses and 'non-severe'
      hemorrhage are managed by omitting a dose or stopping treatment plus
      administering vitamin K depending on the INR. Major bleeding is managed using a
      VKA reversal strategy. A prothrombin complex concentrate infusion plus vitamin K
      is preferred to rapidly achieve an INR of up to 1.5 and maintain a normal
      coagulation profile. The INR must be measured 30 min after the infusion. Before
      an invasive procedure, if an INR of less than 1.5 (<1.3 in neurosurgery) is
      required, it can be achieved by combining prothrombin complex concentrate and
      vitamin K. A well-codified strategy is essential for managing patients requiring
      emergency invasive procedures or presenting bleeding complications.

PMID- 29462054
TI  - We're Not Just Horsing Around: Creating Innovative Community Clinical Experiences
      Utilizing Diverse Opportunities.
AB  - Community nursing clinical experiences are essential to the education of BSN
      prelicensure students. Because of limited traditional community clinical sites,
      faculty must identify innovative, nontraditional community sites that provide
      quality experiences. Faculty at Ohio University identified a unique opportunity
      to provide a multidisciplinary collaborative community clinical rotation in
      conjunction with the Center for Therapeutic Riding Center located at the Ohio
      Horse Park. Nineteen senior BSN students participated in a six-week community
      clinical experience caring for a variety of vulnerable populations participating
      in the therapeutic riding program. Faculty and students responded positively to
      the experience.

PMID- 29462055
TI  - Tap Water and Risk of Acanthamoeba Keratitis in Rigid Gas-Permeable Lens Wearers:
      Sacred Cow or Culprit?

PMID- 29462056
TI  - Exposure to Tap Water Puts a Contact Lens Wearer at Greater Risk of Exposure to
      Acanthamoeba.

PMID- 29462057
TI  - Segmental Spinal Myoclonus Complicating Lumbar Transforaminal Epidural Steroid
      Injection.
AB  - OBJECTIVE: Lumbar transforaminal epidural steroid injection is commonly used for
      treating lumbar radicular pain. We report a case of segmental spinal myoclonus
      that developed during lumbar transforaminal epidural injection with local
      anesthetic and steroid. CASE REPORT: A 58-year-old woman with failed back surgery
      syndrome presented with low back and right L3 and L4 radicular pain. As she had
      responded well previously to diagnostic selective nerve root injection with local
      anesthetic at the right L3 and L4 levels, lumbar transforaminal epidural steroid
      injection at the same levels was scheduled. During injection of ropivacaine and
      triamcinolone at the right L3-4 intervertebral foramen, she complained of back
      pain and immediately developed involuntary contraction of her right hip. The
      procedure was terminated. No new neurological deficit was detected when she was
      examined 15 minutes after the procedure. There were no abnormalities from blood
      tests and magnetic resonance imaging of the lower thoracic and lumbar spine. A
      neurologist subsequently made the clinical diagnosis of segmental spinal
      myoclonus. The myoclonus improved over 1 month and eventually resolved
      completely. CONCLUSIONS: Segmental spinal myoclonus is a rare complication after
      lumbar transforaminal epidural steroid and local anesthetic injection. Pain
      physicians should be aware of this potential complication.

PMID- 29462058
TI  - Comparison of Paravertebral Block by Anatomic Landmark Technique to Ultrasound
      Guided Paravertebral Block for Breast Surgery Anesthesia: A Randomized Controlled
      Trial.
AB  - BACKGROUND AND OBJECTIVES: Paravertebral block (PVB) is an established technique
      for providing anesthesia for breast surgery. The primary objective was to compare
      anatomical landmark technique (ALT) to the ultrasound-guided (USG) PVB block for
      providing surgical anesthesia. Secondary objectives included comparison of
      perioperative analgesia and complications. METHODS: This randomized, controlled,
      observer-blinded study included 72 females, aged 18 to 65 years, American Society
      of Anesthesiologists physical status I or II, undergoing elective unilateral
      breast surgery. Study participants were randomized to the ALT group or USG group.
      Ipsilateral PVB was performed with the respective technique from T1 to T6. Five
      milliliters of local anesthetic mixture (0.5% ropivacaine, 5 MUg/mL adrenaline, 1
      MUg/kg clonidine) was administered at each level. Paravertebral catheter was
      inserted at T4/T3 level. After confirming sensory loss, patients were taken up
      for surgery with propofol sedation (20-50 MUg/kg per minute). RESULTS: More
      patients in the USG group (34/36 [94.44%]) had a successful block as compared
      with the ALT group (26/36 [72.22%]) (P = 0.024). Difference in proportion was
      18.1 (95% confidence interval, 0.15-36.0) (P = 0.024) after adjustment for age.
      More dermatomes were blocked in the USG group (P = 0.0018) with less sparing of
      upper T2 and T3 dermatomes (P = 0.003, P = 0.006, respectively). Median time to
      first postoperative analgesic requirement was 502.5 minutes (range, 195-1440
      minutes) in the USG group versus 377.5 minutes (range, 215-1440 minutes) in the
      ALT group. Pain at rest and movement 2 and 4 hours postoperatively and number of
      catheter top-ups in 24 hours postoperatively were lesser in the USG group (P =
      0.012). Complications were comparable. CONCLUSIONS: Ultrasound-guided PVB
      provided better anesthesia and perioperative analgesia than the landmark
      technique for breast surgery. CLINICAL TRIAL REGISTRATION: The trial was
      registered retrospectively at the Clinical Trial Registry of India,
      CTRI/2015/05/005774.

PMID- 29462059
TI  - Effects of Ultra-early Hyperbaric Oxygen Therapy on Femoral Calcitonin Gene
      Related Peptide and Bone Metabolism of Rats With Complete Spinal Transection.
AB  - STUDY DESIGN: Seventy-five Sprague-Dawley rats were randomly divided into sham,
      complete spinal cord transection (CSCT) and hyperbaric oxygen (HBO) groups. Among
      them, rats in HBO group were further divided into 3 hours group (HBO1) and 12
      hours group (HBO2). OBJECTIVE: To study the effects of ultra-early HBO therapy on
      femoral calcitonin gene-related peptide (CGRP) and bone metabolism of rats with
      CSCT. SUMMARY OF BACKGROUND DATA: Complete spinal cord injury (SCI) is still an
      unresolved problem in clinical practice. Studies on changes in (calcitonin gene
      related peptide) CGRP and bone metabolism and osteoporosis prevention after SCI
      have important clinical significance. METHODS: Rats in the sham group underwent
      laminectomy alone, whereas rats in the other three groups underwent laminectomy
      and CSCT at the level of the 10th thoracic vertebra. Six weeks after operation,
      rat blood samples and femoral samples from CSCT area were taken and prepared for
      immunohistochemical staining of CGRP, quantitative polymerase chain reaction
      (qPCR) of CGRP mRNA, enzyme-linked immunosorbent assay (ELISA) for the levels of
      serum bone-specific alkaline phosphatase (sBAP), serum osteocalcin (sOC), serum
      type-I collagen amino-terminal peptide (sNTX), and urinary deoxypyridinoline
      (uDPD). These data were statistically analyzed using paired LSD or Tamhane.
      RESULTS: The number of CGRP-positive cells and expression of CGRP mRNA in femur
      were significantly reduced, and the levels of sBAP, sOC, sNTX, and uDPD were
      significantly increased in CSCT, HBO1, and HBO2 groups than in the sham group, (P
      < 0.05-0.01). In addition, the number of CGRP-positive cells, expression of CGRP
      mRNA in femur, and the levels of sBAP and sOC were significantly enhanced, but
      the levels of sNTX and uDPD were significantly lowered in HBO1 group than in HBO2
      and CSCT groups (P < 0.05). CONCLUSION: Ultra-early HBO therapy could improve
      bone turnover, promote bone formation, and prohibit bone resorption by enhancing
      CGRP synthesis in the sensory neurons in posterior horn of spinal cord. LEVEL OF
      EVIDENCE: N/A.

PMID- 29462060
TI  - Iliac Crest Bone Graft for Minimally Invasive Transforaminal Lumbar Interbody
      Fusion: A Prospective Analysis of Inpatient Pain, Narcotics Consumption, and
      Costs.
AB  - STUDY DESIGN: Retrospective Analysis OBJECTIVE.: The aim of this study was to
      determine whether an association between increased acute pain, postoperative
      time, and direct hospital costs exists between the use of iliac crest bone
      grafting (ICBG) and bone morphogenic protein (BMP)-2 following a primary, single
      level minimally invasive transforaminal lumbar interbody fusion (MIS TLIF).
      SUMMARY OF BACKGROUND DATA: ICBG has been associated with enhanced fusion rates.
      Concerns have been raised in regards to increased operative time and
      postoperative pain. The advantages of ICBG compared to other spinal fusion
      adjuncts have been debated. METHODS: Prospective, consecutive analysis of
      patients undergoing primary, single-level MIS TLIF with ICBG was compared to a
      historical cohort of consecutive patients that received BMP-2. Operative
      characteristics were compared between groups using chi analysis or independent t
      test for categorical and continuous variables, respectively. Postoperative
      inpatient pain was measured using the Visual Analog Scale, and inpatient
      narcotics consumption was quantified as oral morphine equivalents. Outcomes were
      compared between groups using multivariate regression controlling for
      preoperative characteristics. RESULTS: A total of 98 patients were included in
      this analysis, 49 in each cohort. No significant differences were noted between
      cohorts with exception to sex (Females: ICBG, 53.06% vs. BMP-2, 32.65%, P =
      0.041). There was a significant increase in operative time (14.53 minutes, P =
      0.006) and estimated blood loss (16.64 mL, P = 0.014) in the ICBG cohort.
      Narcotics consumption was similar between groups on postoperative days 0 and 1.
      ICBG was associated with decreased total direct costs ($19,315 vs. $21,645, P <
      0.001) as compared to BMP-2. CONCLUSION: Patients undergoing MIS TLIF with ICBG
      experienced increases in operative time and estimated blood loss that were not
      clinically significant. Furthermore, iliac crest harvesting did not result in an
      increase in acute pain or narcotics consumption. Further follow-up is necessary
      to determine the associated arthrodesis rates and long-term outcomes between each
      cohort. LEVEL OF EVIDENCE: 3.

PMID- 29462061
TI  - Visual Loss Following Spine Surgery: What Have We Seen Within the Scoliosis
      Research Society Morbidity and Mortality Database?
AB  - STUDY DESIGN: A retrospective review of the Scoliosis Research Society (SRS)
      morbidity and mortality (M&M) database. OBJECTIVE: The aim of this study was to
      investigate visual related complications in spinal deformity patients undergoing
      spine surgery. SUMMARY OF BACKGROUND DATA: The SRS compiles surgeon-reported
      complications into an M&M database, tracking postoperative complications
      including visual loss, neurological deficits, infections, and death. Limited
      literature exists on postoperative visual complications, a rare but devastating
      complication following spine surgery. METHODS: We utilized the SRS M&M database
      to determine demographics, perioperative risk factors, and prognosis for visual
      related complications in spinal deformity patients undergoing corrective spine
      surgery from 2009 to 2012. RESULTS: A total of 167,972 spinal deformity patients
      from 2009 to 2012 were identified with a visual acuity complication (VAC) rate of
      0.01%, or 12.5 per 100,000 patients. VAC rates for patients with kyphosis were
      significantly higher than patients with scoliosis (0.049% vs. 0.010%, P = 0.002)
      and spondylolisthesis (0.049% vs. 0.005%, P = 0.001). Postoperative visual loss
      rates significantly decreased from 2010 to 2012 (0.022% vs. 0.004%, P = 0.029).
      Twenty-one patients identified with VACs had a mean age of 34.8 +/- 24.3 years.
      Two (9.5%) patients had preoperative vision changes, two (9.5%) were diabetic,
      two (9.5%) had vascular disease, one (4.8%) had a history of thromboembolic
      disease, and five (23.8%) had hypertension. Extent of VAC was bilateral-partial
      in four (19.0%), bilateral-total in five (23.8%), unilateral-partial in eight
      (38.1%), and unilateral-total in three (14.3%) patients. Four (19.0%) patients
      developed anterior ischemic optic neuropathy, four (19.0%) had posterior ischemic
      optic neuropathy (PION), five (23.8%) had central retinal artery occlusion, and
      five (23.8%) developed cortical blindness (CB). Greater than 50% of the VACs
      occurred on, or before, the first postoperative day. Ten (47.6%) patients
      recovered complete vision and four (19.0%) improved. All patients with CB and 50%
      with posterior ischemic optic neuropathy experienced complete resolution.
      CONCLUSION: VACs occur in approximately 12.5 per 100,000 deformity patients, with
      a rate five times higher in patients with kyphosis. More than 50% of these
      complications occur within 24 hours postoperatively. Nearly half of these
      complications resolve completely, and another 19% improve postoperatively. LEVEL
      OF EVIDENCE: 4.

PMID- 29462062
TI  - Back Pain and Co-occurring Conditions: Findings From a Nationally Representative
      Sample.
AB  - STUDY DESIGN: Cross-sectional population-level health survey. OBJECTIVE: To
      describe the frequency of co-occurring conditions with back pain; to identify
      risk factors for back pain controlling for co-occurring conditions; and to
      examine the association between back pain and individual co-occurring conditions.
      SUMMARY OF BACKGROUND DATA: Back pain shares risk factors with a range of other
      conditions. Most studies have considered risk factors for back pain without
      taking into account the potential influence of co-occurring conditions. METHODS:
      Analysis of the 2013 Canadian Community Health Survey (n = 61,854, age >=15 yr).
      Back pain status and co-occurring conditions were determined from questions about
      long-term health conditions diagnosed by a health profession. Multivariable log
      Poisson regression analysis was used to assess the adjusted association of back
      pain with demographic and lifestyle characteristics and co-occurring conditions.
      RESULTS: The population prevalence of reported back pain was 19.3%. Most (71%)
      reported at least one co-occurring condition. Most frequently reported were
      arthritis (35%), high blood pressure (26%), migraine (18%), and mood disorders
      (14%). Following the addition of co-occurring condition count to the regression
      model, being female and being overweight/obese were no longer significantly
      associated with back pain, and the associations with ages 45 to 54 years and
      older, low-income, smoking, and being physical inactive were significantly
      attenuated. The highest prevalence ratio, 3.32 (95% confidence interval: 3.06
      3.59), was for 3+ co-occurring conditions. In multivariable regression all but a
      few individual chronic conditions remained significant associated with back pain.
      CONCLUSION: Established risk factors for back pain may be largely a reflection of
      shared risk factors with co-occurring conditions. The high frequency of co
      occurring conditions likely reflects diverse mechanisms related to heterogeneity
      of back pain. The extent of association of co-occurring conditions with back pain
      has implications for clinical management and need for further research to
      characterize subgroups. LEVEL OF EVIDENCE: 2.

PMID- 29462063
TI  - Depression is Closely Associated With Chronic Low Back Pain in Patients Over 50
      Years of Age: A Cross-sectional Study Using the Sixth Korea National Health and
      Nutrition Examination Survey (KNHANES VI-2).
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVE: This study was designed to
      analyze the relationship between the presence and severity of depression and low
      back pain (LBP) in a representative sample of the general population using a self
      report screening questionnaire for depression. SUMMARY OF BACKGROUND DATA: There
      is increasing evidence supporting an association between depression and LBP.
      However, the degree of the association between these two conditions in the
      general population is poorly understood. METHODS: Health surveys and examinations
      were conducted on a nationally representative sample (n = 7550) of Koreans. LBP
      status was determined by a simple survey response concerning LBP >30 days during
      the past 3 months. Depression was defined as individuals with a total score >10
      on the Patient Health Questionnaire (PHQ)-9 survey. The severity of depression
      was categorized as none (0-4), mild (5-9), moderate (10-14), moderately severe
      (15-19), and severe (20-27) according to PHQ-9 score. Data regarding
      demographics, socioeconomic history, and comorbid health conditions were used to
      analyze adjusted, weighted logistic regression models. RESULTS: In the Korean
      population, the prevalence of depression was significantly greater in individuals
      with LBP (20.3%) than in those without LBP (4.5%). On multivariate logistic
      regression analysis, the presence of depression was significantly associated with
      LBP (adjusted odd ratio [aOR]: 3.93, P < 0.001). The risk of LBP increased with
      increasing severity of depression as follows: severe depression (aOR: 9.28, P <
      0.001), moderately severe depression (aOR: 3.24, P = 0.001), moderate depression
      (aOR: 4.97, P < 0.001), and mild depression (aOR: 2.48, P < 0.001). CONCLUSION:
      Depression is more common in patients with LBP among Koreans. The presence of
      depression was significantly associated with LBP, especially in severely
      depressed individuals. LEVEL OF EVIDENCE: 3.

PMID- 29462064
TI  - Health-related Quality of Life of Adolescents With Severe Untreated Congenital
      Kyphosis and Kyphoscoliosis in a Developing Country.
AB  - STUDY DESIGN: A cross-sectional study OBJECTIVE.: The aim of this study was to
      study the health-related quality of life (HRQOL) of adolescents with severe
      untreated congenital kyphosis (CK) and congenital kyphoscoliosis (CKS) in a
      developing country. SUMMARY OF BACKGROUND DATA: Surgical intervention is
      generally indicated early in patients with progressive CK or CKS to prevent the
      progression of deformity and to improve the quality of life of the patients.
      HRQOL of adolescents with untreated CK and CKS in developing countries has never
      been investigated. METHODS: Arabic version of the Scoliosis Research Society 22
      revision (SRS-22r) questionnaire used to study HRQOL of adolescents with severe
      untreated CK or CKS in a dev eloping country. RESULTS: A total of 134 adolescent
      (mean age 17.1 years) completed SRS-22r questionnaire: 38 patients with CK from
      80 degrees  to 110 degrees  (group 1), 24 patients with CK > 110 degrees  (group
      2), 27 patients with CKS (group 3), and 45 healthy controls (group 4). Group 1
      had significant lower scores than group 4 in all SRS 22r domains (P < 0.001).
      Scores of all domains except pain showed significant (P < 0.001) decrease with
      increase of the severity of CK. Group 3 had significant lower scores than group 2
      in all SRS-22r domains except mental health. Satisfaction domain had significant
      lower scores than all other SRS-22r domains for group 1, 2, and 3. All patients
      of groups 2 and 3 gave the minimum answers for satisfaction domain questions. A
      total of 69%, 84% and 94% of group 1, 2, and 3, respectively, gave the minimum
      answer when asked whether their back condition affects their personal
      relationships. Female patients of group 1, 2, and 3 had significant lower scores
      for self-image domain. CONCLUSION: HRQOL is severely affected in adolescents with
      untreated severe CK and CKS in a developing country. LEVEL OF EVIDENCE: 3.

PMID- 29462065
TI  - Biomechanical Comparison of Four Different Atlantoaxial Posterior Fixation
      Constructs in Adults: A Finite Element Study.
AB  - STUDY DESIGN: Finite element analysis. OBJECTIVE: To compare the biomechanical
      stability imparted to the C1 and C2 vertebrae by the transarticular (TA), C1
      lateral mass (LM)-C2 pedicle (PS), C1LM-C2 pars, and C1LM-C2 translaminar (TL)
      screw fixation techniques. SUMMARY OF BACKGROUND DATA: Cadaveric biomechanical
      studies of several atlantoaxial posterior fixation techniques have been
      performed, showing significant heterogeneity in biomechanical properties among
      the studies. METHODS: From computed tomography images, a nonlinear intact three
      dimensional C1-2 finite element model was developed and validated. Four finite
      element models were reconstructed from different C1-2 fixation techniques. The
      range of motion (ROM) and maximum von Misses stresses for the four screw
      techniques were compared under flexion, extension, lateral bending, and axial
      rotation. RESULTS: C1LM-C2PS showed the greatest decrease in ROM with
      flexion/extension and lateral bending. C1-2TA and C1LM-C2 pars showed less ROM
      reduction than the other techniques, in flexion/extension. C1LM-C2TL showed the
      least decrease in ROM during axial rotation. For C1-2TA, the maximum stress was
      in the C1-2 joint region. In the C1LM-C2PS, the C1 rod head, C2 pars screw, and
      C2TL screw were stressed at the C2 rod head. The maximal von Mises stress on the
      C1-2TA at the C1-2 joint site was the highest at flexion/extension, whereas the
      C1LM-C2PS had the lowest stress on the screw at flexion/extension and lateral
      bending. The C1LM-C2TL showed the highest stress in axial rotation and lateral
      bending. CONCLUSION: In this study, C1LM-C2PS fixation was the most stable
      technique. If surgeons have to use other fixation methods besides the C2 pedicle
      screw, they need to be aware that additional fixation or postoperative
      immobilization may be required to achieve ROM restriction. Careful observation at
      the maximum stress site on the screw including screw loosening, screw-bone
      interface disruption or screw fracture will be necessary during follow-up imaging
      examinations (x-ray and computed tomography scan) after atlantoaxial fixation.
      LEVEL OF EVIDENCE: N/A.

PMID- 29462066
TI  - Outcomes of Surgical Decompression in Patients With Very Severe Degenerative
      Cervical Myelopathy.
AB  - STUDY DESIGN: A prospective observational international study. OBJECTIVE: The aim
      of this study was to evaluate outcomes of decompressive surgery in patients with
      very severe degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA:
      Although decompressive surgery has been evidenced as a safe and effective
      approach for patients with myelopathic deficiencies, studies have suggested
      residual disability following treatment in patients with more severe disease
      presentation. METHODS: Postoperative outcomes of 60 patients with very severe DCM
      (modified Japanese Orthopaedic Association [mJOA] score <=8) were compared to
      outcomes of 188 patients with severe DCM (mJOA 9-11). Postimputation follow-up
      rate was 93.1%. Unadjusted and adjusted analyses were performed using two-way
      repeated measures of covariance. RESULTS: The two cohorts were similar in
      demographics, length of duration of myelopathy symptoms, source of stenosis, and
      surgical approaches used to decompress the spine. The very severe and severe
      cohorts differed in preoperative Nurick grades (4.97 vs. 3.91, respectively, P <
      0.0001) and Neck Disability Index scores (45.20 vs. 56.21, respectively, P =
      0.0006). There were no differences in Short Form 36 (SF-36v2) physical (PCS) and
      mental (MCS) component summary scores. Both cohorts improved in mJOA, Nurick,
      Neck Disability Index, and SF-36v2 PCS and MCS scores. Despite the substantial
      postoperative improvements, patients in both cohorts had considerable residual
      symptoms. Two-thirds of the patients in the very severe cohort had severe (mJOA
      <=11) or moderate (mJOA <= 14) myelopathy symptoms at 24 months follow-up. Longer
      duration of disease was associated with poorer treatment response. CONCLUSION:
      Decompressive surgery is effective in patients with very severe DCM; however,
      patients have significant residual symptoms and disability. The very severe
      subgroup (mJOA <=8) of patients with DCM represents a distinct group of patients
      and their different clinical trajectory is important for clinicians and patients
      to recognize. Duration of symptoms negatively affects chances for recovery.
      Whenever possible, patients with DCM should be treated before developing very
      severe symptomatology. LEVEL OF EVIDENCE: 2.

PMID- 29462067
TI  - Postoperative Walking Ability of Non-ambulatory Cervical Myelopathy Patients.
AB  - STUDY DESIGN: A retrospective analysis. OBJECTIVE: The aim of this study was to
      clarify the postoperative improvement of walking ability and prognostic factors
      in nonambulatory patients with cervical myelopathy. SUMMARY OF BACKGROUND DATA:
      Many researchers have reported the surgical outcome in compressive cervical
      myelopathy. However, regarding severe gait disturbance,, it has not been
      clarified yet how much improvement can be expected. METHODS: One hundred thirty
      one nonambulatory patients with cervical myelopathy were treated surgically and
      followed for an average of 3 years. Walking ability was graded according to the
      lower-extremity function subscore (L/E subscore) in Japanese Orthopedic
      Association score. We divided patients based on preoperative L/E subscores: group
      A, L/E subscore of 1 point (71 patients); and group B, 0 or 0.5 point (60
      patients). The postoperative walking ability was graded by L/E subscore:
      excellent, >=2 points; good, 1.5 points; fair, 1 point; and poor, 0.5 or 0
      points. We compared preoperative and postoperative scores. The cutoff value of
      disease duration providing excellent improvement was investigated. RESULTS:
      Overall, 50 patients were graded as excellent (38.2%), and 21 patients were
      graded as good (16.0%). In group B, 17 patients (28.3%) were graded as excellent.
      Seventeen patients who were graded as excellent had shorter durations of
      myelopathic symptoms and/or gait disturbance (7.9 and 3.8 months respectively)
      than the others (29.5 and 8.9 months, respectively) (P < 0.05). Receiver
      operating characteristic curve showed that the optimal cutoff values of the
      duration of myelopathic symptoms and gait disturbance providing excellent
      improvement were 3 and 2 months, respectively. CONCLUSION: Even if the patients
      were nonambulatory, 28.3% of them became able to walk without support after
      operation. If a patient becomes nonambulatory within 3 months from the onset of
      myelopathy or 2 months from the onset of gait disturbance, surgical treatment
      should be performed immediately to raise the possibility to improve stable gait.
      LEVEL OF EVIDENCE: 3.

PMID- 29462068
TI  - Risk Factors of Impaired Pulmonary Function in Arthrogryposis Multiplex
      Congenital Patients With Concomitant Scoliosis: A Comparison With Adolescent
      Idiopathic Scoliosis.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the severity of
      pulmonary function impairment for arthrogryposis multiplex congenital (AMC)
      patients with concomitant scoliosis and to determine risk factors associated with
      the impaired pulmonary function in these patients. SUMMARY OF BACKGROUND DATA:
      AMC patients are generally believed to have impaired pulmonary function. However,
      the severity of respiratory morbidity and the associated risk factors have not
      been reported. METHODS: The pulmonary function tests data including the
      percentage predicted values of forced vital capacity (%FVC), forced expiratory
      volume in 1 second (%FEV1), and the ratio of FEV1 to FVC (%FEV1/FVC) were
      reviewed and compared for 48 AMC patients with secondary scoliosis and 48
      patients with adolescent idiopathic scoliosis. The radiographic parameters of
      coronal and sagittal plane deformities and body mass index (BMI) were measured
      and correlated with impaired pulmonary function in these AMC patients. RESULTS:
      AMC patients with concomitant scoliosis had significant lower mean %FVC, %FEV1,
      and %FEV1/FVC than adolescent idiopathic scoliosis patients (48.8 vs. 70.3 for
      %FVC, P < 0.001; 45.3 vs. 69.7 for %FEV1, P < 0.001; 92.1 vs. 96.9 for %FEV1/FVC,
      P < 0.05, respectively). Seventy percent of AMC patients had severe pulmonary
      function impairment. A positive correlation was found between BMI and %FVC and
      %FEV1 (P < 0.01) and between hypokyphosis and %FVC and %FEV1 (P < 0.05). A
      negative correlation was found between coronal angle and pulmonary function (P <
      0.05). Multiple regression analysis showed that all of the three variables were
      independent predictors associated with a reduced pulmonary function. With a
      combination of these variables, the multiple regression model could account for
      38.7% of the variance in %FVC and 41.5% in %FEV1. CONCLUSION: There exists severe
      impairment of pulmonary function in AMC patients with concomitant scoliosis. The
      scoliotic curve, hypokyphosis, and BMI were independent risk factors associated
      with the pulmonary dysfunction in these patients. As the majority of the
      variability of impaired pulmonary function tests are still poorly understood,
      more risk factors await to be uncovered in future studies. LEVEL OF EVIDENCE: 4.

PMID- 29462069
TI  - The Association Between Body Mass Index and the Prevalence, Severity, and
      Frequency of Low Back Pain: Data From the Osteoarthritis Initiative.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To determine whether there is an
      association between body mass index (BMI) and the prevalence, severity, and
      frequency of low back pain and identify other potential patient risk factors for
      the development of low back pain. SUMMARY OF BACKGROUND DATA: Many studies have
      implicated that a high BMI is a risk factor for low back pain. However, few
      studies have examined the association between increased BMI and the prevalence,
      severity, and frequency of low back pain. METHODS: Data from the Osteoarthritis
      Initiative, a multicenter, prospective study of knee osteoarthritis, were used to
      conduct this study, which included 4796 patients. BMI was categorized according
      to the World Health Organization classification and the prevalence, severity, and
      frequency of low back pain were assessed. Logistic regression was performed to
      identify additional patient risk factors associated with low back pain. RESULTS:
      The prevalence of low back pain was found to be significantly higher in patients
      with an elevated BMI compared to those with normal or underweight BMI and
      demonstrated a stepwise increase with each BMI category. Approximately 47.4% of
      patients with normal or underweight BMI complained of low back pain compared with
      72.8% of morbidly obese patients (P < 0.0001). No association was seen between
      BMI and the frequency or severity of low back pain episodes. Osteoarthritis of
      the back and depression were patient variables found to be associated with all
      three measures (prevalence, severity, and frequency) of low back pain.
      CONCLUSION: Elevated BMI is strongly associated with an increased prevalence of
      low back pain. Depression and osteoarthritis of the back are associated with the
      prevalence, severity, and frequency of low back pain. LEVEL OF EVIDENCE: 3.

PMID- 29462070
TI  - Bisphosphonate and Teriparatide Use in Thoracolumbar Spinal Fusion: A Systematic
      Review and Meta-analysis of Comparative Studies.
AB  - STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare the
      efficacy of the use of either bisphosphonates or teriparatide on radiographic and
      functional outcomes of patients that had thoracolumbar spinal fusion. SUMMARY OF
      BACKGROUND DATA: Controversy exists as to whether bisphosphonates interfere with
      successful spinal arthrodesis. An alternative osteoporosis medication is
      teriparatide, a synthetic parathyroid hormone that has an anabolic effect on
      osteoblast function. To date, there is limited comparative data on the influence
      of bisphosphonates or teriparatide on spinal fusion. METHODS: A systematic search
      of medical reference databases was conducted for comparative studies on
      bisphosphonate or teriparatide use after thoracolumbar spinal fusion. Meta
      analysis was performed using the random-effects model for heterogeneity.
      Radiographic outcomes assessed include fusion rates, risk of screw loosening,
      cage subsidence, and vertebral fracture. RESULTS: No statistically significant
      differences were noted between bisphosphonates and control groups regarding
      fusion rate and risk of screw loosening (fusion: odds ratio [OR] = 2.2, 95%
      confidence interval [CI]: 0.87-5.56, P = 0.09; loosening: OR = 0.45, 95% CI: 0.14
      1.48, P = 0.19). Teriparatide use was associated with higher fusion rates than
      bisphosphonates (OR = 2.3, 95% CI: 1.55-3.42, P < 0.0001). However, no
      statistically significant difference was noted between teriparatide and
      bisphosphonates regarding risk of screw loosening (OR = 0.37, 95% CI: 0.12-1.18,
      P = 0.09). Lastly, bisphosphonate use was associated with decreased odds of cage
      subsidence and vertebral fractures compared to controls (subsidence: OR = 0.29,
      95% CI 0.11-0.75, P = 0.01; fracture: OR = 0.18, 95% CI 0.07-0.48, P = 0.0007).
      CONCLUSION: Bisphosphonates do not appear to impair successful spinal fusion
      compared to controls although teriparatide use is associated with higher fusion
      rates than bisphosphonates. In addition, bisphosphonate use is associated with
      decreased odds of cage subsidence and vertebral fractures compared to controls
      that had spinal fusion. LEVEL OF EVIDENCE: 3.

PMID- 29462071
TI  - The Relationship Between Improvements in Myelopathy and Sagittal Realignment in
      Cervical Deformity Surgery Outcomes.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: Determine whether alignment or
      myelopathy improvement drives patient outcomes after cervical deformity (CD)
      corrective surgery. SUMMARY OF BACKGROUND DATA: CD correction involves
      radiographic malalignment correction and procedures to improve motor function and
      pain. It is unknown whether alignment or myelopathy improvement drives patient
      outcomes. METHODS: Inclusion: Patients with CD with baseline/1-year radiographic
      and outcome scores. Cervical alignment improvement was defined by improvement in
      Ames CD modifiers. modified Japanese Orthopaedic Association (mJOA) improvement
      was defined as mild [15-17], moderate [12-14], severe [<12]. Patient groups
      included those who only improved in alignment, those who only improved in mJOA,
      those who improved in both, and those who did not improve. Changes in quality-of
      life scores (neck disability index [NDI], EuroQuol-5 dimensions [EQ-5D], mJOA)
      were evaluated between groups. RESULTS: A total of 70 patients (62 yr, 51% F)
      were included. Overall preoperative mJOA score was 13.04 +/- 2.35. At baseline,
      21 (30%) patients had mild myelopathy, 33 (47%) moderate, and 16 (23%) severe.
      Out of 70 patients 30 (44%) improved in mJOA and 13 (18.6%) met 1-year mJOA
      minimal clinically important difference. Distribution of improvement groups:
      16/70 (23%) alignment-only improvement, 13 (19%) myelopathy-only improvement, 18
      (26%) alignment and myelopathy improvement, and 23 (33%) no improvement. EQ-5D
      improved in 11 of 16 (69%) alignment-only patients, 11 of 18 (61%)
      myelopathy/alignment improvement, 13 of 13 (100%) myelopathy-only, and 10 of 23
      (44%) no myelopathy/alignment improvement. There were no differences in
      decompression, baseline alignment, mJOA, EQ-5D, or NDI between groups. Patients
      who improved only in myelopathy showed significant differences in baseline-1Y EQ
      5D (baseline: 0.74, 1 yr:0.83, P < 0.001). One-year C2-S1 sagittal vertical axis
      (SVA; mJOA r = -0.424, P = 0.002; EQ-5D r = -0.261, P = 0.050; NDI r = 0.321, P =
      0.015) and C7-S1 SVA (mJOA r = -0.494, P < 0.001; EQ-5D r = -0.284, P = 0.031;
      NDI r = 0.334, P = 0.010) were correlated with improvement in health-related
      qualities of life. CONCLUSION: After CD-corrective surgery, improvements in
      myelopathy symptoms and functional score were associated with superior 1-year
      patient-reported outcomes. Although there were no relationships between cervical
      specific sagittal parameters and patient outcomes, global parameters of C2-S1 SVA
      and C7-S1 SVA showed significant correlations with overall 1-year mJOA, EQ-5D,
      and NDI. These results highlight myelopathy improvement as a key driver of
      patient-reported outcomes, and confirm the importance of sagittal alignment in
      patients with CD. LEVEL OF EVIDENCE: 3.

PMID- 29462072
TI  - Anterior to Dorsal Root Entry Zone Myelotomy (ADREZotomy): A New Surgical
      Approach for the Treatment of Ventrolateral Deep Intramedullary Spinal Cord
      Cavernous Malformations.
AB  - STUDY DESIGN: A retrospective review of prospectively collected data. OBJECTIVE:
      To confirm the feasibility of using anterior to dorsal root entry zone myelotomy
      (ADREZotomy), a new surgical approach, for the treatment of ventrolateral deep
      intramedullary spinal cord cavernous malformation (ISCCMs). SUMMARY OF BACKGROUND
      DATA: Surgical removal of ventrolateral deep ISCCMs is highly risky and remains
      problematic. METHODS: The authors performed a retrospective study exploring the
      surgical removal of ventrolateral intrinsic ISCCMs using ADREZotomy in 10
      patients. The Frankel grading system was used to evaluate the patients'
      neurological function at the preoperative, postoperative and follow-up stages.
      American Spinal Injury Association Scale scores at the preoperative and
      postoperative were also obtained. The patient characteristics and surgical
      outcomes were analyzed. The indication, operative steps, complications, and
      anatomical basis of the myelotomies were described and discussed. RESULTS: In
      total, nine (90%) patients presented with mild symptoms before surgery. Gross
      total resections were performed in all 10 patients. Immediately after surgery,
      the neurological function of eight (80.0%) patients remained the same. One
      patient improved and one (10%) patient worsened. There were no other immediate or
      delayed complications related to the surgical procedure. No decrease of total
      American Spinal Injury Association sensory scores was observed. The follow-up
      neurological function evaluation showed that two (20%) patients improved from a
      Frankel grade of D to E and eight (80.0%) patients were stable. No recurrences or
      other additional neurological deterioration was observed. CONCLUSION: Surgical
      removal of ventrolateral deep ISCCMs can be feasible using proper surgical
      techniques. ADREZotomy is a minimally invasive technique for the removal of
      cervical and thoracic ventrolateral deep ISCCMs, without disrupting the important
      spinal cord tracts or the need to broadly expose bone. LEVEL OF EVIDENCE: 4.

PMID- 29462073
TI  - Cancer Nurses Can Bridge the Gap Between the Specialist Cancer Care and Primary
      Care Settings to Facilitate Shared-Care Models.

PMID- 29462074
TI  - Radial Shaft Convergence in Distal Radius Fractures: Diagnosis and Treatment.
AB  - Radial shaft convergence in distal radius fractures is often misdiagnosed. This
      common deformation is often associated with a radial translation of the distal
      fragment. This parameter has to be corrected because of the increased risk of
      distal radioulnar joint instability due to detensioning of the distal
      interosseous membrane if there is an associated triangular fibrocartilage complex
      lesion. A new radiologic sign for diagnosis of proximal radius convergence during
      distal radius fracture is presented as well as technical tips for correction of
      this deformity.

PMID- 29462075
TI  - Hospital Characteristics Associated With Postdischarge Hospital Readmission,
      Observation, and Emergency Department Utilization.
AB  - BACKGROUND: Whether types of hospitals with high readmission rates also have high
      overall postdischarge acute care utilization (including emergency department and
      observation care) is unknown. DESIGN: Cross-sectional analysis. SUBJECTS:
      Nonfederal United States acute care hospitals. MEASURES: Using methodology
      established by the Centers for Medicare & Medicaid Services, we calculated each
      hospital's "excess days in acute care" for fee-for-service (FFS) Medicare
      beneficiaries aged over 65 years discharged after hospitalization for acute
      myocardial infarction, heart failure (HF), or pneumonia, representing the mean
      difference between predicted and expected total days of acute care utilization in
      the 30 days following hospital discharge, per 100 discharges. We assessed the
      multivariable association of 8 hospital characteristics with excess days in acute
      care and the proportion of hospitals with each characteristic that were
      statistical outliers (95% credible interval estimate does not include 0).
      RESULTS: We included 2184 hospitals for acute myocardial infarction [228 (10.4%)
      better than expected, 549 (25.1%) worse than expected], 3720 hospitals for HF
      [484 (13.0%) better and 840 (22.6%) worse], and 4195 hospitals for pneumonia [673
      (16.0%) better, 1005 (24.0%) worse]. Results for all conditions were similar.
      Worse than expected outliers for pneumonia included: 18.8% of safety net
      hospitals versus 26.1% of nonsafety net hospitals; 16.7% of public hospitals
      versus 33.1% of for-profit hospitals; 19.5% of nonteaching hospitals versus 52.2%
      of major teaching hospitals; 7.9% of rural hospitals versus 42.1% of large urban
      hospitals; 5.9% of hospitals with 24-<50 beds versus 58% of hospitals with >500
      beds; and 29.0% of hospitals with nurse-to-bed ratios >1.0-1.5 versus 21.7% of
      hospitals with ratios >2.0. CONCLUSIONS: Including emergency department and
      observation stays in measures of postdischarge utilization produces similar
      results as measuring only readmissions in that major teaching, urban and for
      profit hospitals still perform disproportionately poorly versus nonteaching or
      public hospitals. However, it enables identification of more outliers and a more
      granular assessment of the association of hospital factors and outcomes.

PMID- 29462076
TI  - Medicare Advantage Penetration and Hospital Costs Before and After the Affordable
      Care Act.
AB  - BACKGROUND: Research has suggested that growth in the Medicare Advantage (MA)
      program indirectly benefits the entire 65+-year-old population by reducing
      overall expenditures and creating spillover effects of patient care practices.
      Medicare programs and innovations initiated by the Affordable Care Act (ACA) have
      encouraged practices to adopt models applying to all patient populations, which
      may influence the continued benefits of MA program growth. OBJECTIVE: This study
      investigated the relationship between MA program growth and inpatient hospital
      costs and utilization before and after the ACA. METHODS: Primary data sources
      were 2005-2014 Health Care Cost and Utilization Project hospital data and 2004
      2013 Centers for Medicare & Medicaid Services enrollment data. County-year-level
      regression analysis with fixed effects examined the relationship between Medicare
      managed care penetration and hospital cost per enrollee. We decomposed results
      into changes in utilization, severity, and severity-adjusted inpatient resource
      use. Analyses were stratified by whether the admission was urgent or nonurgent.
      PRINCIPAL FINDINGS: A 10% increase in MA penetration was associated with a 3
      percentage point decrease in inpatient cost per Medicare enrollee before the ACA.
      This effect was more prominent in nonurgent admissions and diminished after the
      ACA. CONCLUSIONS: Results suggest that MA enrollment growth is associated with
      diminished spillover reductions in hospital admission costs after the ACA. We did
      not observe a strong relationship between MA enrollment and inpatient days per
      enrollee. Future research should examine whether spillover effects still are
      observed in outpatient settings.

PMID- 29462077
TI  - Maryland Multipayor Patient-centered Medical Home Program: A 4-Year
      Quasiexperimental Evaluation of Quality, Utilization, Patient Satisfaction, and
      Provider Perceptions.
AB  - OBJECTIVE: To evaluate impact of the Maryland Multipayor Patient-centered Medical
      Home Program (MMPP) on: (1) quality, utilization, and costs of care; (2)
      beneficiaries' experiences and satisfaction with care; and (3) perceptions of
      providers. DESIGN: 4-year quasiexperimental design with a difference-in
      differences analytic approach to compare changes in outcomes between MMPP
      practices and propensity score-matched comparisons; pre-post design for patient
      reported outcomes among MMPP beneficiaries. SUBJECTS: Beneficiaries (Medicaid
      insured and privately insured) and providers in 52 MMPP practices and 104 matched
      comparisons in Maryland. INTERVENTION: Participating practices received
      unconditional financial support and coaching to facilitate functioning as medical
      homes, membership in a learning collaborative to promote education and
      dissemination of best practices, and performance-based payments. MEASURES:
      Sixteen quality, 20 utilization, and 13 cost measures from administrative data;
      patient-reported outcomes on care delivery, trust in provider, access to care,
      and chronic illness management; and provider perceptions of team operation, team
      culture, satisfaction with care provided, and patient-centered medical home
      transformation. RESULTS: The MMPP had mixed impact on site-level quality and
      utilization measures. Participation was significantly associated with lower
      inpatient and outpatient payments in the first year among privately insured
      beneficiaries, and for the entire duration among Medicaid beneficiaries. There
      was indication that MMPP practices shifted responsibility for certain
      administrative tasks from clinicians to medical assistants or care managers. The
      program had limited effect on measures of patient satisfaction (although response
      rates were low) and on provider perceptions. CONCLUSIONS: The MMPP demonstrated
      mixed results of its impact and indicated differential program effects for
      privately insured and Medicaid beneficiaries.

PMID- 29462078
TI  - The Impact of a Health Information Technology-Focused Patient-centered Medical
      Neighborhood Program Among Medicare Beneficiaries in Primary Care Practices: The
      Effect on Patient Outcomes and Spending.
AB  - BACKGROUND: The Center for Medicare & Medicaid Innovation (CMMI) tests new models
      of paying for or delivering health care services and expands models that improve
      health outcomes while lowering medical spending. CMMI gave TransforMED, a
      national learning and dissemination contractor, a 3-year Health Care Innovation
      Award (HCIA) to integrate health information technology systems into physician
      practices. This paper estimates impacts of TransforMED's HCIA-funded program on
      patient outcomes and Medicare parts A and B spending. RESEARCH DESIGN: We
      compared outcomes for Medicare fee-for-service (FFS) beneficiaries served by 87
      treatment practices to outcomes for Medicare FFS beneficiaries served by 286
      matched comparison practices, adjusting for differences in outcomes between the 2
      groups during a 1-year baseline period. We estimated impacts in 3 evaluation
      outcome domains: quality-of-care processes, service use, and spending. RESULTS:
      We estimated the program led to a 7.1% reduction in inpatient admissions and a
      5.7% decrease in the outpatient emergency department visits. However, there was
      no evidence of statistically significant effects in outcomes in either the
      quality-of-care processes or spending domains. CONCLUSIONS: These results
      indicate that TransforMED's program reduced service use for Medicare FFS
      beneficiaries, but also show that the program did not have statistically
      significant favorable impacts in the quality-of-care processes or spending
      domains. These results suggest that providing practices with population health
      management and cost-reporting software-along with technical assistance for how to
      use them-can complement practices' own patient-centered medical home
      transformation efforts and add meaningfully to their impacts on service use.

PMID- 29462079
TI  - Care Experiences Among Medicare Beneficiaries With and Without a Personal
      Physician.
AB  - BACKGROUND: Having a "personal" physician is a critical element to care
      continuity. Little is known about which older adults are more likely to lack
      personal physicians and if their care experiences differ from those with a
      personal physician. OBJECTIVE: The objective of this study was to describe care
      experiences and characteristics associated with not having a personal physician.
      RESEARCH DESIGN: We compare rates of lacking a personal physician across
      subgroups. Using doubly robust propensity-score-weighted regression, we compare
      patient experience among beneficiaries with and without a personal physician.
      SUBJECTS: A total of 272,463 nationally representative beneficiaries age 65+
      responding to the 2012 Medicare CAHPS survey. MEASURES: Beneficiary
      characteristics, having a personal physician, 4 patient experience measures.
      RESULTS: Five percent of respondents reported no personal physician. Lacking a
      personal physician was more common for men, racial/ethnic minorities (eg, 16% of
      American Indian/Alaska Natives), and the younger and less educated. Those without
      a personal physician reported substantially poorer experiences on 4 measures
      (P<0.001); these differences are larger than those observed by key demographic
      characteristics. Beneficiaries without a personal physician were more than 3
      times as likely to have not seen any health care provider in the last 6 months.
      CONCLUSIONS: Even with the access provided by Medicare, a small but nontrivial
      proportion of seniors report having no personal physician. Those without a
      personal physician report substantially worse patient experiences and lacking a
      personal physician is more common for some vulnerable groups. This may underlie
      some previously observed disparities. Efforts should be made to encourage and
      help seniors without personal physicians to select one.

PMID- 29462080
TI  - Characterizing injury severity in nonaccidental trauma: Does Injury Severity
      Score miss the mark?
AB  - BACKGROUND: Children suffering nonaccidental trauma (NAT) are at high risk of
      death. It is unclear whether markers of injury severity for trauma center/system
      benchmarking such as Injury Severity Score (ISS) adequately characterize this.
      Our objective was to evaluate mortality prediction of ISS in children with NAT
      compared with accidental trauma (AT). METHODS: Pediatric patients younger than 16
      years from the Pennsylvania state trauma registry 2000 to 2013 were included.
      Logistic regression predicted mortality from ISS for NAT and AT patients.
      Multilevel logistic regression determined the association between mortality and
      ISS while adjusting for age, vital signs, and injury pattern in NAT and AT
      patients. Similar models were performed for head Abbreviated Injury Scale (AIS).
      Sensitivity analysis examined impaired functional independence at discharge as an
      alternate outcome. RESULTS: Fifty thousand five hundred seventy-nine patients
      were included with 1,866 (3.7%) NAT patients. Nonaccidental trauma patients had a
      similar rate of mortality at an ISS of 13 as an ISS of 25 for AT patients.
      Nonaccidental trauma patients also have higher mortality for a given head AIS
      level (range, 1.2-fold to 5.9-fold higher). Injury Severity Score was a
      significantly greater predictor of mortality in AT patients (adjusted odds
      rations [AOR], 1.14; 95% confidence interval [CI], 1.13-1.15; p < 0.01) than NAT
      patients (AOR, 1.09; 95% CI, 1.07-1.12; p < 0.01) per 1-point ISS increase, while
      head injury was a significantly greater predictor of mortality in NAT patients
      (AOR, 3.48; 95% CI, 1.54-8.32; p < 0.01) than AT patients (AOR, 1.21; 95% CI,
      0.95-1.45; p = 0.12). Nonaccidental trauma patients had a higher rate of impaired
      functional independence at any given ISS or head AIS level than AT patients.
      CONCLUSION: Nonaccidental trauma patients have higher mortality and impaired
      function at a given ISS/head AIS than AT patients. Conventional ISS thresholds
      may underestimate risk and head injury is a more important predictor of mortality
      in the NAT population. These findings should be considered in system performance
      improvement and benchmarking efforts that rely on ISS for injury
      characterization. LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 29462081
TI  - The opioid epidemic in acute care surgery-Characteristics of overprescribing
      following laparoscopic cholecystectomy.
AB  - BACKGROUND: Postoperative prescribing following acute care surgery must be
      optimized to limit excess opioids in circulation as misuse and diversion are
      frequently preceded by a prescription for acute pain. This study aimed to
      identify patient characteristics associated with higher opioid prescribing
      following laparoscopic cholecystectomy (LC). METHODS: Among patients aged 18
      years or older who underwent LC at a single institution in 2014 to 2016, opioids
      prescribed at discharge were converted to oral morphine equivalents (OME) and
      compared with developing state guidelines (maximum, 200 OME). Preoperative opioid
      use was defined as any opioid prescription 1 month to 3 months before LC or a
      prescription unrelated to gallbladder disease less than 1 month before LC.
      Univariate and multivariable methods determined characteristics associated with
      top quartile opioid prescriptions among opioid-naive patients. RESULTS: Of 1,606
      LC patients, 34% had emergent procedures, and 14% were preoperative opioid users.
      Nonemergent LC patients were more likely to use opioids preoperatively (16% vs.
      11%, p = 0.006), but median OME did not differ by preoperative opioid use (225
      vs. 219, p = 0.40). Among 1,376 opioid-naive patients, 96% received opioids at
      discharge. Median OME was 225 (interquartile range, 150-300), and 52% were
      prescribed greater than 200 OME. Top quartile prescriptions (>=300 OME) were
      associated with gallstone pancreatitis diagnosis, younger age, higher pain
      scores, and longer length of stay (all p < 0.05). While median OME did not differ
      by emergent status (median, 225; interquartile range, 150-300 for both, p =
      0.15), emergent had more top quartile prescriptions (32% vs. 25%, p = 0.005).
      After adjusting for diagnosis, age, and sex, emergent status showed evidence of
      being associated with top quartile prescription (odds ratio, 1.3; 95% confidence
      interval, 1.0-1.8). Thirty-day refill rate was 5%. CONCLUSION: Over half of
      opioid-naive patients undergoing LC were prescribed opioids exceeding draft state
      guidelines. Variation in prescribing patterns was not fully explained by patient
      factors. Acute care surgeons have an opportunity to optimize prescribing
      practices with the ultimate goal of reducing opioid misuse. LEVEL OF EVIDENCE:
      Therapeutic study, level IV; Epidemiologic study, level III.

PMID- 29462082
TI  - A novel, minimally invasive approach to assure hemostasis for intercostal
      bleeding after trauma.
AB  - Intercostal artery injury can cause large hemothoraces. While many patients with
      intercostal artery injury present hemodynamically unstable and require emergent
      thoracotomy for hemostasis, some tamponade spontaneously. They may rebleed later,
      however, and cause recurrent hemothorax or retained hemothorax. Video-assisted
      thoracic surgery (VATS) is an effective way to evacuate retained hemothorax.
      However, assessing and ligating intercostal artery injury during VATS can be
      difficult, and often, open thoracotomy is pursued. Even with open surgery,
      ligation of the intercostal artery can be a challenge. We present a minimally
      invasive method of definitive intercostal artery ligation during VATS or open
      thoracotomy.

PMID- 29462083
TI  - Tourniquet usage in prehospital care and resuscitation of pediatric trauma
      patients-Pediatric Trauma Society position statement.
AB  - BACKGROUND: Recent mass casualty events in the United States have highlighted the
      need for public preparedness to prevent death from uncontrolled hemorrhage. The
      Pediatric Trauma Society (PTS) reviewed the literature regarding pediatric
      tourniquet usage with the aim to provide recommendations about the utility of
      this adjunct for hemorrhage control in children. METHODS: Search terms
      "pediatric" and "tourniquet" were used to query the US National Library of
      Medicine National Institutes of Health for pertinent literature. Exclusion
      criteria include not involving children, not involving the use of an extremity
      tourniquet, primary outcomes not related to hemorrhage control, tourniquet use to
      prevent snake envenomation, single case reports, and only foreign language
      formats available. Bibliographies of remaining studies reviewed to identify
      additional pertinent research. Four physician members of the PTS Guidelines
      Committee reviewed identified studies. RESULTS: One hundred thirty-four studies
      were identified. One hundred twenty-three studies were excluded. Seven additional
      studies were identified through bibliography review. Eighteen pertinent studies
      were reviewed. Seven articles evaluated physiologic response to tourniquet use in
      operating room settings. Six articles were generated from combat experience in
      conflicts in Afghanistan and Iraq. Four articles discussed technical details of
      tourniquet usage. One article evaluated the use of tourniquets during the Boston
      Marathon bombing in 2015. CONCLUSION: Despite limited data of limited quality
      regarding their use, the PTS supports the usage of tourniquets in the prehospital
      setting and during the resuscitation of children suffering from exsanguinating
      hemorrhage from severe extremity trauma. Expedited, definitive care must be
      sought, and tourniquet pressure and time should be limited to the least amount
      possible. The Society supports the ACS "Stop the Bleed" campaign and encourages
      further investigation of tourniquet use in children. LEVEL OF EVIDENCE:
      Guidelines/algorithm study, level IIIa.

PMID- 29462084
TI  - Physician training in critical care in the United States: Update 2018.
AB  - Critical care fellowship training in the United States differs based on specific
      specialty and includes medicine, surgery, anesthesiology, pediatrics, emergency
      medicine, and neurocritical care training pathways. We provide an update
      regarding the number and growth of US critical care fellowship training programs,
      on-duty residents and certified diplomates, and review the different critical
      care physician training pathways available to residents interested in pursuing a
      fellowship in critical care. Data were obtained from the Accreditation Council
      for Graduate Medical Education and specialty boards (American Board of Internal
      Medicine, American Board of Surgery, American Board of Anesthesiology, American
      Board of Pediatrics American Board of Emergency Medicine) and the United Council
      for Neurologic Subspecialties for the last 16 years (2001-2017). The number of
      critical care fellowship training programs has increased 22.6%, with a 49.4%
      increase in the number of on-duty residents annually, over the last 16 years.
      This is in contrast to the period of 1995 to 2000 when the number of physicians
      enrolled in critical care fellowship programs had decreased or remained
      unchanged. Although more than 80% of intensivists in the US train in internal
      medicine critical care Accreditation Council for Graduate Medical Education
      approved fellowships, there has been a significant increase in the number of
      residents from surgery, anesthesiology, pediatrics, emergency medicine, and other
      specialties who complete specialty fellowship training and certification in
      critical care. Matriculation in neurocritical care fellowships is rapidly rising
      with 60 programs and over 1,200 neurocritical care diplomates. Critical care is
      now an increasingly popular fellowship in all specialties. This rapid growth of
      all critical care specialties highlights the magnitude of the heterogeneity that
      will exist between intensivists in the future.

PMID- 29462085
TI  - Nonocclusive mesenteric ischemia in patients with methamphetamine use.
AB  - BACKGROUND: Data suggest that methamphetamine may increase the risk of
      nonocclusive mesenteric ischemia (NOMI). We describe patterns of presentation and
      outcomes of patients with methamphetamine use who present with NOMI to a single
      institution. METHODS: This is an observational study of patients from January
      2015 to September 2017 with methamphetamine use who presented with NOMI at an
      academic medical center in Northern California. We summarize patient
      comorbidities, clinical presentation, operative findings, pathologic findings,
      hospital course, and survival. RESULTS: Ten patients with methamphetamine use and
      severe NOMI were identified. One patient was readmitted with a perforated
      duodenal ulcer, for a total of 11 encounters. Most presented with acute (n = 3)
      or acute-on-chronic (n = 4) abdominal pain. Distribution of ischemia ranged from
      perforated duodenal ulcer (n = 3), ischemia of the distal ileum (n = 1), ischemia
      of entire small bowel (n = 2), and patchy necrosis of entire small bowel and
      colon (n = 5). Six patients died, three within 1 week of admission and three
      between 3 months and 8 months. CONCLUSION: Methamphetamine use may be associated
      with significant microvascular compromise, increasing the risk of mesenteric
      ischemia. Providers in areas with high prevalence of methamphetamine use should
      have a high index of suspicion for intestinal ischemia in this patient
      population. Patients with methamphetamine use admitted for trauma or other
      pathology may be at particular risk of ischemia and septic shock, especially in
      the setting of dehydration. Use of vasoconstrictors in this patient population
      may also exacerbate intestinal ischemia. LEVEL OF EVIDENCE: Therapeutic Case
      series study, level V.

PMID- 29462086
TI  - Emergency sternal intraosseous access for warm fresh whole blood transfusion in
      damage control resuscitation.
AB  - BACKGROUND: Intraosseous (IO) vascular access is increasingly used as an
      emergency tool for achieving access to the systemic circulation in critically ill
      patients. The role of IO transfusion of blood in damage control resuscitation is
      however questionable due to possible inadequate flow rate and hemolysis. Some
      experts claim that IO transfusion is contraindicated. In this study, we have
      challenged this statement by looking at flow rates of autologous fresh whole
      blood reinfusion and hemolysis using two of the commonly used Food and Drug
      Administration-approved and Conformite Europeenne (CE)-marked sternal needles.
      Additionally, the success rate of sternal access between the two devices is
      evaluated. METHODS: Volunteer professional military personnel, were enrolled
      prospectively in a nonrandomized observational study design. We collected 450 mL
      of autologous whole blood from each participant. Participants were divided into
      the following three groups of 10: Tactically Advanced Lifesaving IO Needle
      (T.A.L.O.N.) IO, FAST1 IO, and intravenous group. The reinfusion was done by
      gravity only. Blood sampling was performed before blood collection and 30 minutes
      after reinfusion. Investigation of hemolysis was performed by measurements of
      haptoglobin and lactate dehydrogenase. Success rate was evaluated by correct
      aspiration of bone marrow. RESULTS: Median reinfusion rate was 46.2 mL/min in the
      FAST1 group, 32.4 mL/min in the T.A.L.O.N. group, and 74.1 mL/min in the
      intravenous group. Blood samples from all participants were within normal ranges.
      There was no statistically significant difference in haptoglobin and lactate
      dehydrogenase between the groups. In the FAST1 group, 1 (9%) of 11 procedures
      failed. In the T.A.L.O.N. group, 4 (29%) of 14 procedures failed. CONCLUSION:
      Although preferable, achieving peripheral venous access in the bleeding patient
      is a major problem. Our findings suggest that fresh whole-blood transfusion
      through the IO route is safe, reliable, and provide sufficient flow for
      resuscitation. LEVEL OF EVIDENCE: Therapeutic/Care management study, level III.

PMID- 29462087
TI  - Prognosis of diffuse axonal injury with traumatic brain injury.
AB  - BACKGROUND: Determine the prognostic impact of magnetic resonance imaging (MRI)
      defined diffuse axonal injury (DAI) after traumatic brain injury (TBI) on
      functional outcomes, quality of life, and 3-year mortality. METHODS: This
      retrospective single center cohort included adult trauma patients (age > 17
      years) admitted from 2006 to 2012 with TBI. Inclusion criteria were positive head
      computed tomography with brain MRI within 2 weeks of admission. Exclusion
      criteria included penetrating TBI or prior neurologic condition. Separate ordinal
      logistic models assessed DAI's prognostic value for the following scores: (1)
      hospital-discharge Functional Independence Measure, (2) long-term Glasgow Outcome
      Scale-Extended, and (3) long-term Quality of Life after Brain Injury-Overall
      Scale. Cox proportional hazards modeling assessed DAI's prognostic value for 3
      year survival. Covariates included age, sex, race, insurance status, Injury
      Severity Score, admission Glasgow Coma Scale Score, Marshall Head computed
      tomography Class, clinical DAI on MRI (Y/N), research-level anatomic DAI Grades I
      III (I, cortical; II, corpus callosum; III, brainstem), ventilator days, time to
      follow commands, and time to long-term follow-up (for logistic models). RESULTS:
      Eligibility criteria was met by 311 patients, who had a median age of 40 years
      (interquartile range [IQR], 23-57 years), Injury Severity Score of 29 (IQR, 22
      38), intensive care unit stay of 6 days (IQR, 2-11 days), and follow-up of 5
      years (IQR, 3-6 years). Clinical DAI was present on 47% of MRIs. Among 300
      readable MRIs, 56% of MRIs had anatomic DAI (25% Grade I, 18% Grade II, 13% Grade
      III). On regression, only clinical (not anatomic) DAI was predictive of a lower
      Functional Independence Measure score (odds ratio, 2.5; 95% confidence interval,
      1.28-4.76], p = 0.007). Neither clinical nor anatomic DAI were related to
      survival, Glasgow Outcome Scale-Extended, or Quality of Life after Brain Injury
      Overall Scale scores. CONCLUSION: In this longitudinal cohort, clinical evidence
      of DAI on MRI may only be useful for predicting short-term in-hospital functional
      outcome. Given no association of DAI and long-term TBI outcomes, providers should
      be cautious in attributing DAI to future neurologic function, quality of life,
      and/or survival. LEVEL OF EVIDENCE: Epidemiological, level III; Therapeutic,
      level IV.

PMID- 29462088
TI  - Vascular surgery during U.S. combat operations from 2002 to 2016: Analysis of
      vascular procedures performed to inform military training.
AB  - BACKGROUND: Vascular surgery constitutes approximately 6.5% of surgical
      procedures performed for combat injuries, yet general surgeons are increasingly
      unfamiliar with vascular surgery. This study examines the frequency and type of
      vascular surgical procedures performed during recent US Military operations from
      2002 to 2016. METHODS: A retrospective analysis of the Department of Defense
      Trauma Registry was performed for all Role (R)2 and R3 medical treatment
      facilities (MTFs), from January 2002 to May 2016. A total of 106 International
      Classification of Diseases-9th Rev.-Clinical Modification (ICD-9-CM) procedure
      codes were categorized as vascular and were included in the present analysis.
      Procedure codes were separated by anatomic location and procedure type. Ligation
      as part of an amputation was excluded. Grafts were further subdivided by type:
      synthetic, autologous, and unknown. Procedure grouping and categorization were
      determined by subject matter experts. Data analysis used Stata Version 14
      (College Station, TX). RESULTS: A total of 25,816 vascular surgical procedures
      were identified at R2 and R3 MTFs. Role 3 MTFs reported more than four times the
      number of procedures compared to R2 MTFs. The most common anatomic locations
      documented were extremity (64.96%) and not otherwise specified (28.1%). The most
      common procedures overall were amputation (33.36%) and fasciotomy (18.83%). The
      most common graft type was autologous (68.87%), and the least common was
      synthetic (5.69%). CONCLUSION: While amputation, fasciotomy, and ligation were
      the most common vascular procedures performed for combat trauma, the need for
      definitive repair including grafting is common at both R2 and R3 MTFs. Vascular
      surgery therefore remains a necessary skill set for the deployed US Military
      surgeon; military general surgeons need to train and sustain their vascular
      skills, including proficiency at amputation and fasciotomy. LEVEL OF EVIDENCE:
      Epidemiologic study, level III.

PMID- 29462089
TI  - Evaluation of the management of severe trauma kidney injury and long-term renal
      function in children.
AB  - BACKGROUND: To evaluate the management and long-term renal function with DMSA
      scintigraphy in pediatric severe traumatic kidney injury grade IV and V at the
      trauma center of Grenoble Teaching Hospital. METHODS: This is a single-center
      observational retrospective study between 2004 and 2014. All children younger
      than 15 years and managed at the Grenoble teaching Hospital for a severe trauma
      kidney injury grade IV or V were included. The trauma grade was radiologically
      diagnosed on arrival at hospital, using the classification of the American
      Association for Surgery of Trauma. The management followed the algorithm in
      effect in the establishment. The assessment of the renal function was performed
      by a DMSA scintigraphy after at least 6 months from the injury. RESULTS: Twenty
      one children were managed for a severe renal trauma (16 IV and 5 V). The
      diagnosis was initially made by an ultrasonography (eight cases) or a computed
      tomography scan (13 cases). A child with a severe renal trauma IV underwent
      nephrectomy on day 6 of the trauma. Eleven children needed a therapeutic
      procedure (three embolizations, four double J stents, one arterial stent, one
      peritoneal lavage for a splenic hemoperitoneum, four pleural drainages). A DMSA
      scintigraphy was performed in 15 patients to assess the function of the injured
      kidney: 11 of 16 severe renal trauma IV with an average of 39.4%, and 17% in 4 of
      5 severe renal trauma V analyzed. CONCLUSION: Among the 21 children managed for a
      severe kidney trauma injury IV or V, 11 required a therapeutic procedure, one of
      them a nephrectomy. The DMSA scintigraphy performed after at least 6 months from
      the trauma found an injured renal function at 39.4% in 11 of 16 severe renal
      trauma IV analyzed, and 17% in 4 of 5 severe renal trauma V analyzed, which
      confirms the currently conservative management. LEVEL OF EVIDENCE: Type of study:
      original article, retrospective observational study, level IV.

PMID- 29462090
TI  - Breslow Density Is a Novel Prognostic Feature That Adds Value to Melanoma
      Staging.
AB  - Histomorphologic prognostic biomarkers that can be measured using only an
      hematoxylin and eosin stain are very attractive because they are simple and
      cheap. We conceived an entirely novel biomarker of this type, the Breslow density
      (BD), which measures invasive melanoma cell density at the site where Breslow
      thickness (BT) is measured. This study assessed BD's prognostic value. In this
      study, BD was measured in 1329 melanoma patients. Measurement accuracy and
      precision was assessed using intraclass correlation coefficient (ICC). Survival
      was assessed with a primary end-point of melanoma-specific survival (MSS) and
      also overall survival and metastasis-free survival. We found that BD measurement
      was accurate compared with gold standard image analysis (ICC, 0.84). Precision
      was excellent for 3 observers with different experience (ICC, 0.93) and for an
      observer using only written instructions (ICC, 0.93). BD was a highly significant
      predictor in multivariable analysis for overall survival, MSS, and metastasis
      free survival (each, P<0.001) and it explained MSS better than BT, but BT and BD
      together had best explanatory capability. A BD cut point of >=65% was trained in
      970 melanomas and validated in 359. This cut point showed promise as a novel way
      to upstage melanoma from T stage "a" to "b." BD was combined with BT to create a
      targeted burden score. This was a validated as an adjunct to American Joint
      Committee on Cancer stage. In summary, BD can be measured accurately and
      precisely. It demonstrated independent prognostic value and explained MSS better
      than BT alone. Notably, we demonstrated ways that BD could be used with American
      Joint Committee on Cancer version 8 staging.

PMID- 29462091
TI  - Distinct Genomic Copy Number Alterations Distinguish Mucinous Tubular and Spindle
      Cell Carcinoma of the Kidney From Papillary Renal Cell Carcinoma With Overlapping
      Histologic Features.
AB  - Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare type
      of renal cell carcinoma that frequently exhibits histologic and immunophenotypic
      features overlapping with type 1 papillary renal cell carcinoma (PRCC). To
      clarify molecular attributes that can be used for this difficult differential
      diagnosis, we sought to delineate the genome-wide copy number alterations in
      tumors displaying classic histologic features of MTSCC in comparison to the solid
      variant of type 1 PRCC and indeterminate cases with overlapping histologic
      features. The study included 11 histologically typical MTSCC, 9 tumors with
      overlapping features between MTSCC and PRCC, and 6 cases of solid variant of type
      1 PRCC. DNA samples extracted from macrodissected or microdissected tumor areas
      were analyzed for genome-wide copy number alterations using an SNP-array platform
      suitable for clinical archival material. All cases in the MTSCC group exhibited
      multiple chromosomal losses, most frequently involving chromosomes 1, 4, 6, 8, 9,
      13, 14, 15, and 22, while lacking trisomy 7 or 17. In contrast, cases with
      overlapping morphologic features of MTSCC and PRCC predominantly showed multiple
      chromosomal gains, most frequently involving chromosomes 7, 16, 17, and 20,
      similar to the chromosomal alteration pattern that was seen in the solid variant
      of type 1 PRCC cases. Morphologic comparison of these molecularly characterized
      tumors identified histologic features that help to distinguish MTSCC from PRCC,
      but immunohistochemical profiles of these tumors remained overlapping, including
      a marker for Hippo-Yes-associated protein signaling. Characteristic patterns of
      genome-wide copy number alterations strongly support MTSCC and PRCC as distinct
      entities despite their immunohistochemical and certain morphologic overlap, and
      help define histologic features useful for the classification of questionable
      cases.

PMID- 29462092
TI  - Significance of T1a and T1b Carcinoma Arising in Mucinous Cystic Neoplasm of
      Pancreas.
AB  - Mucinous cystic neoplasm (MCN) of pancreas is one of the precursor lesions of
      pancreatic ductal adenocarcinoma. The 5-year disease-specific survival for
      noninvasive MCNs was 100% and 20% to 60% for those with pancreatic ductal
      adenocarcinoma arising in a MCN. However, the significance of T1a (<=0.5 cm) and
      T1b (>0.5 and <1.0 cm) carcinoma arising in MCN as defined by the upcoming
      American Joint Committee on Cancer, eighth edition is unclear. In this study, we
      examined 3 cases of MCN with T1a or T1b carcinoma and compared their
      clinicopathologic characteristics and survival to 46 cases of MCN with low-grade
      dysplasia (MCN-LGD), 7 cases of MCN with high-grade dysplasia (MCN-HGD), and 7
      cases of MCN with advanced invasive carcinoma (T2 or higher T stage). The tumors
      from all 3 cases were submitted in their entirety in 123, 296, and 200 blocks,
      respectively. All 3 patients were alive with no recurrence during the follow-up
      of 20.0, 113.8, and 137.2 months, respectively. Similarly, none of the patients
      who had MCN with either LGD or HGD had recurrence or died of disease. In
      contrast, 5 of 7 patients who had MCN with advanced invasive carcinoma had
      recurrence and later died of disease with a median survival of 22.9 months
      (P<0.001). Our study showed that MCN with T1a and T1b carcinoma had an excellent
      prognosis similar to MCNs with LGD or HGD after complete tumor sampling for
      histologic examination. Our results along with the previous studies suggest that
      close follow-up, rather than aggressive systemic therapy, may be a better
      approach for these patients.

PMID- 29462093
TI  - Contraception for midlife women: a review.
AB  - Family planning represents a key component of reproductive health care.
      Accordingly, the provision of contraception must span the reproductive age
      spectrum, including perimenopause. The risk of pregnancy is decreased, but not
      trivial, among women over 40 years of age. Evidence-based guidelines for
      contraceptive use can assist clinicians in counseling their patients in this
      population. Intrauterine contraception is one of the most effective methods and
      is safe to use in midlife women with few exceptions. Progestin-only contraception
      is another safe option for most midlife women because it is not associated with
      an increased risk of cardiovascular complications. Combined (estrogen-containing)
      contraception can be safely used by midlife women who do not have cardiovascular
      risk factors. Unique noncontraceptive benefits for this population include:
      improvement in abnormal uterine bleeding, decreased hot flashes, and decreased
      cancer risk. Finally, guidelines state that contraception can be used by midlife
      women without medical contraindications until the age of menopause, at which time
      they may consider transition to systemic hormone therapy.

PMID- 29462094
TI  - Effects of abaloparatide on bone mineral density and risk of fracture in
      postmenopausal women aged 80 years or older with osteoporosis.
AB  - OBJECTIVE: Advanced age is an important risk factor for fracture. The
      Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) trial showed that
      subcutaneous abaloparatide increased bone mineral density (BMD) and reduced the
      risk of vertebral and nonvertebral fractures in postmenopausal women with
      osteoporosis. This study describes the effects of abaloparatide in the subgroup
      of women aged 80 or more years in ACTIVE. METHODS: Post hoc analyses of BMD and
      fracture incidence in this subgroup of women who received abaloparatide or
      placebo in the 18-month, phase 3, double-blind, randomized controlled ACTIVE
      trial. RESULTS: The mean ages of the women >=80 years were 81.9 and 81.7 years in
      the placebo (n = 43) and abaloparatide (n = 51) groups, respectively. The
      increases in BMD from baseline to 18 months with abaloparatide treatment were
      3.9% at the total hip (P < 0.001), 3.6% at the femoral neck (P < 0.01), and 12.1%
      at the lumbar spine (P < 0.001), and were similar to those observed in the
      overall population. Abaloparatide therapy was associated with numerical, but not
      statistically significant, reductions in the risk of vertebral and nonvertebral
      fractures in this subpopulation, compared with placebo. The proportion of
      participants reporting adverse events was similar between treatment groups and
      between the older subgroup and the overall population. CONCLUSION: Abaloparatide
      was effective in increasing BMD in the very elderly subgroup of ACTIVE, with a
      safety profile similar to that of the overall study population.

PMID- 29462095
TI  - Hormonal, metabolic, and endometrial safety of testosterone vaginal cream versus
      estrogens for the treatment of vulvovaginal atrophy in postmenopausal women: a
      randomized, placebo-controlled study.
AB  - OBJECTIVE: The aim of the study was to evaluate the laboratory and endometrial
      safety of topical testosterone versus topical estrogen for the treatment of
      vaginal atrophy in postmenopausal women. METHODS: This was a randomized, placebo
      controlled trial of 60 postmenopausal women aged 40 to 70 years at the Menopause
      Clinic of CAISM UNICAMP. Women were randomized into three vaginal treatment
      groups: estrogen, testosterone, or placebo. The treatment was applied 3 times a
      week for 12 weeks. Hormonal laboratory values of follicle-stimulating hormone,
      luteinizing hormone, estradiol, estrone, androstenedione, total testosterone,
      free testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and
      sex hormone-binding globulin were assessed at baseline and at 6 and 12 weeks.
      Metabolic laboratory values of total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate
      aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma
      glutamyl transpeptidase were also assessed at baseline and at 6 and 12 weeks.
      Endometrial safety was assessed using ultrasonography at baseline and at 12
      weeks. RESULTS: After 12 weeks of treatment, there were no significant
      differences in hormonal or metabolic laboratory values among all three groups.
      Two participants in the estrogen group had increased serum estradiol after 12
      weeks of treatment. No change in endometrial thickening was reported in all three
      groups. CONCLUSIONS: Twelve weeks of treatment with topical testosterone or
      estrogen in postmenopausal women with symptoms of vaginal atrophy demonstrated
      laboratory and endometrial safety when compared with placebo.

PMID- 29462096
TI  - Patterns of menopausal hormone therapy use and hyperkyphosis in older women.
AB  - OBJECTIVE: Hyperkyphosis, an exaggerated anterior curvature of the thoracic
      spine, is associated with poor physical function, falls, fractures, and earlier
      mortality. Low bone mineral density, bone loss, and vertebral fractures are
      strong risk factors for hyperkyphosis. Menopausal hormone therapy (HT) reverses
      bone loss, prevents vertebral fractures, and, therefore, we hypothesize, may
      reduce the risk for developing hyperkyphosis. METHODS: We evaluated the cross
      sectional association between Cobb angle of kyphosis from lateral spine
      radiographs and pattern of self-reported HT use during the prior 15-year period
      in 1,063 women from the Study of Osteoporotic Fractures. RESULTS: Participants
      had a mean age of 83.7 +/- 3.3 years and a mean Cobb angle of 51.3 +/- 14.6
      degrees . Forty-six per cent of women were characterized as never-users of HT,
      24% as remote past users, 17% as intermittent users, and 12% as continuous users.
      In minimally adjusted models, the mean Cobb angle was 4.0 degrees  less in
      continuous HT users compared with never-users (P = 0.01); however, in fully
      adjusted models, this association was attenuated to 2.8 degrees  (P = 0.06).
      Remote past HT users had 3.0 degrees  less kyphosis compared with never-users in
      minimally adjusted models (P = 0.01), attenuated to 2.8 degrees  less in fully
      adjusted models (P = 0.02). Intermittent users did not differ from never-users in
      degree of kyphosis. CONCLUSIONS: Women reporting continuous or remote past HT use
      had less pronounced kyphosis than never-users by their mid-eighties, suggesting a
      possible role for HT in the prevention of age-related hyperkyphosis.

PMID- 29462097
TI  - Detection of Spatiotemporal Asymmetry in Pro Level Soccer Players.
AB  - Knudsen, NS and Andersen, TB. Detection of spatiotemporal asymmetry in pro level
      soccer players. J Strength Cond Res 32(3): 798-804, 2018-Several papers have
      focused on change of direction (COD) asymmetry investigated through standardized
      tests, and used this information to provide some spatiotemporal insight during
      games. The aim of this study was to investigate asymmetry in the reachable areas
      of the players through actual position data from soccer games. Sixteen
      professional players from the Danish Superliga participated in this study, but 5
      were excluded because of lack of participation throughout the investigated games.
      The reachable areas of the players were investigated at varying sprint velocities
      (1-7 m.s) and within varying time intervals (0.5-4 seconds). The analysis found 7
      players having spatiotemporal asymmetries in their reachable areas (0.5-3%) and
      shift of center of reachable area (4-29 cm). Four players (LB, RB, DM, and CF)
      had spatiotemporal asymmetries that could be attributed to COD and thus
      physiological asymmetries, whereas 3 players (LCB, LW, and RW) had spatiotemporal
      asymmetries that might be caused by their position or by use of tactic. This type
      of asymmetry was named a tactical spatiotemporal asymmetry. Coaches with
      knowledge about spatiotemporal asymmetries can use these actively in their
      tactical approach using the players' asymmetries in synergy, using opponents'
      asymmetries or improving the existing postgame spatiotemporal analyzing tools.

PMID- 29462098
TI  - Clinical Site Development for the Clinical Nurse Leader in a Rural Primary Care
      Setting.

PMID- 29462099
TI  - Impact of a Restraint Management Bundle on Restraint Use in an Intensive Care
      Unit.

PMID- 29462100
TI  - Exercise Training in "At-Risk" Black and White Women: A Comparative Cohort
      Analyses.
AB  - PURPOSE: Few data on the effect of exercise interventions in black women at risk
      for cardiovascular disease are available. METHODS: Women >=18 yr of age without
      known cardiovascular disease with >=1 coronary risk factor were enrolled in a
      community-based exercise program >=3 d.wk for >=30 min per session for 6 months.
      Exercise training intensity ~50% to 80% of functional capacity, using heart rate
      (HR) and/or rating of perceived exertion (RPE) as the primary intensity
      modulators. Preconditioning versus postconditioning quality of life assessments
      (depression and level of daytime sleepiness), dietary fat intake, Duke Activity
      Status Index score, changes in cardiovascular efficiency (systolic/diastolic
      blood pressure (SBP/DBP), HR, RPE during a standardized submaximal workload), and
      anthropometric measures, including body weight, body mass index, and waist
      circumference, were evaluated. RESULTS: Of 556 volunteers, 143 were excluded,
      leaving 413 women (222 white, 191 black; mean +/- SD age, 61 +/- 9 yr) who met
      compliance criteria. Both groups demonstrated significant (P < 0.05)
      postconditioning decreases in body mass index, waist circumference, resting
      SBP/DBP, and total and LDL cholesterol, and reductions in HR, SBP/DBP, and RPE at
      a fixed submaximal workload, and in fat screener, depression, and sleep scores.
      Duke Activity Status Index scores increased significantly (P < 0.0001) for both
      groups, signifying increases in self-reported functional capacity. Although 87
      women (21%) experienced a musculoskeletal injury/discomfort during the program,
      there were no exercise-related cardiovascular events. CONCLUSIONS: A progressive
      moderate-to-vigorous exercise intervention without preliminary exercise testing
      elicited comparable improvements in coronary risk factors, anthropometric and
      quality of life measures, and cardiovascular efficiency in "at-risk" black and
      white women. These adaptations were achieved at exercise levels below those
      recommended in contemporary physical activity guidelines.

PMID- 29462101
TI  - Predicting Diaphyseal Cortical Bone Status Using Measures of Muscle Force
      Capacity.
AB  - PURPOSE: Muscle cross-sectional area (MCSA) is often used as a surrogate for the
      forces applied to bones during physical activity. Although MCSA is a strong
      predictor of cortical bone status, its use makes assumptions about the
      relationship between muscle size and force that are inaccurate. Furthermore, to
      measure MCSA and other muscle force surrogates typically requires expensive
      and/or radiative laboratory equipment. Thus, this study aimed to determine
      whether clinical laboratory- and field-based methodologies for measuring muscular
      force capacity accounted for similar variance in diaphyseal cortical bone status
      as a commonly used muscular force surrogate, MCSA, at the midtibia in young men
      and women. METHODS: Healthy young adults (n = 142, 19.7 +/- 0.7 yr old, 52.8%
      female) were assessed via peripheral quantitative computed tomography at the
      midtibia for cortical bone status and MCSA. Muscle force capacity was measured
      via Biodex dynamometer, Nottingham leg extensor power rig, and Vertec vertical
      jump. Regression analysis compared the independent variance predicted by each
      muscle force measure with that of MCSA, accounting for relevant confounders.
      RESULTS: MCSA, knee extension peak torque, and peak anaerobic power from vertical
      jump were independent predictors of select cortical structural outcomes (cortical
      thickness and area, periosteal and endosteal circumference, and estimated
      strength) accounting for up to 78.4% of the variance explained (all P < 0.05).
      However, cortical volumetric bone mineral density was unrelated to any measure or
      surrogate of muscle force capacity. CONCLUSIONS: MCSA is a strong independent
      predictor of cortical bone structure; however, both laboratory- and field-based
      measures of peak torque and/or peak anaerobic power are promising alternatives,
      explaining similar and sometimes greater variance than MCSA.

PMID- 29462102
TI  - Physical Activity Alters Inflammation in Older Adults by Different Intensity
      Levels.
AB  - PURPOSE: To examine the influence of reallocating time spent at different
      objectively measured physical activity (PA) behaviors on markers of systemic
      inflammation in older women with different levels of metabolic risk. METHODS:
      Accelerometer-based monitoring of PA was conducted in a population of community
      dwelling older women (n = 111; age, 65-70 yr) for determination of daily
      sedentary time, time in light PA (LPA) and moderate-to-vigorous PA (MVPA). Blood
      samples were collected for the assessment of the systemic inflammatory markers C
      reactive protein (CRP), fibrinogen, and adiponectin. Metabolic risk was assessed
      by standardized procedures based on definitions for the metabolic syndrome. Data
      were analyzed by linear regression models based on isotemporal substitution
      analysis. RESULTS: Reallocating 30 min of sedentary time with either time in LPA
      (beta = -0.47; P < 0.05) or MVPA (beta = -0.42; P < 0.05) was related to reduced
      fibrinogen level, whereas no corresponding effect was evident when shifting time
      in LPA with time in MVPA, while holding sedentary time constant. In contrast,
      reallocating a 30-min period in sedentary (beta = -0.70; P < 0.01) or LPA (beta =
      -0.71; P < 0.01) with MVPA was associated with a significant reduction in CRP
      level, whereas no impact on CRP was observed when a period of sedentary behavior
      was replaced with LPA. Importantly, all significant influences on fibrinogen and
      CRP by displacement of different PA behaviors remained after adjustment for
      metabolic risk status among participants. No significant associations with
      adiponectin were observed. CONCLUSIONS: Altogether, this work supports the
      existence of different intensity thresholds mediating beneficial effects of PA on
      important clinical markers of systemic inflammation in older women across
      different stages of disease prevention.

PMID- 29462103
TI  - Hospital, Maternal and Birth Factors Associated With Hepatitis B Vaccination at
      Birth: West Virginia, 2015.
AB  - BACKGROUND: Hepatitis B virus is a bloodborne pathogen typically transmitted
      through sexual contact, injection drug use or perinatally. A hepatitis B vaccine
      (HepB) is available; the first dose is recommended at birth. We sought to
      identify hospital policy, maternal characteristics and birth factors associated
      with HepB receipt at birth in West Virginia. METHODS: We conducted a
      retrospective cohort study of West Virginia live births in 2015 using vital
      records matched to immunization registry records to determine frequency of HepB
      birth dose receipt (<3 days postdelivery). We surveyed all West Virginia birthing
      facilities in 2015 (N = 26) about perinatal hepatitis B virus prevention
      policies. We examined associations of hospital policy, maternal characteristics
      and birth factors with HepB receipt at birth by using a mixed-effects regression
      model to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals
      (CIs). RESULTS: Of 17,458 births, 14,006 (80.2%) infants received a HepB birth
      dose. Hospital use of preprinted newborn routine admission vaccination orders was
      associated with HepB birth dose receipt (aPR: 10.60; 95% CI: 2.12-52.72). Not
      using illicit drugs during pregnancy, maternal age <35 years and weekday births
      were associated with HepB birth dose receipt (aPR: 1.81; 95% CI: 1.54-2.13; aPR:
      1.34, 95% CI: 1.17-1.54 and aPR: 1.15; 95% CI: 1.03-1.28, respectively).
      CONCLUSIONS: Hospitals using preprinted admission orders had higher frequencies
      of HepB birth dose receipt. Additional study is needed to identify HepB birth
      dose receipt barriers among infants with maternal illicit drug use, maternal age
      >=35 years or deliveries during a weekend.

PMID- 29462104
TI  - High Incidence of Tuberculosis Infection in HIV-exposed Children Exiting an
      Isoniazid Preventive Therapy Trial.
AB  - Young HIV-exposed children are at high risk for TB infection. We performed
      QuantiFERON-TB Gold among HIV-exposed children in South Africa at enrolment and 1
      year follow-up. The incidence of TB infection was high for HIV+ (11 cases per 100
      child-years) and HIV-exposed uninfected children (15 cases per 100 child-years).
      QuantiFERON-TB Gold may identify HIV-exposed children at risk for TB disease
      progression.

PMID- 29462105
TI  - Group A Streptococcal Brain Abscess in the Pediatric Population: Case Series and
      Review of the Literature.
AB  - BACKGROUND: Group A Streptococcus (GAS) is a rare cause of central nervous system
      infections. METHODS: We describe 3 new cases of GAS brain abscess in previously
      healthy children treated by us between 2015 and 2016 and review the 5 cases
      reported in the literature since 1988. RESULTS: All 8 children received early
      empiric antibiotic therapy and surgical intervention, and 5 made a full recovery.
      CONCLUSIONS: GAS brain abscess is a rare infection; however its incidence may be
      rising. We suggest that if patients show symptoms such as fever, vomiting and
      lethargy, with contiguous infection such as otitis media, mastoiditis, sinusitis
      or meningitis, GAS brain abscess should be suspected. Prognosis is expected to be
      good with early implementation of appropriate treatment.

PMID- 29462106
TI  - Prevalence of Occult Bacteremia in Infants With Very High Fever Without a Source.
AB  - We carried out a prospective registry-based cohort study at the emergency
      department of 363 previously healthy well-appearing infants 3-24 months of age
      with fever without a source >=40.5 degrees C based on local protocol. Four were
      diagnosed with occult bacteremia (1.1%; 95% confidence interval: 0-2.2).
      Recommendations for nontesting for occult bacteremia screening in these children
      may have to be reconsidered when fever >=40.5 degrees C. Larger studies are
      needed to confirm these results.

PMID- 29462107
TI  - Tracheal Microbiota in Patients With a Tracheostomy Before, During and After an
      Acute Respiratory Infection.
AB  - Examining tracheal microbiota before, during and after acute respiratory
      infection in patients with a tracheostomy demonstrated large baseline
      intrapatient microbiota variability and a significant bloom of Haemophilus and
      Moraxella on day 1 of acute respiratory infection symptoms. The tracheal
      microbiota community composition changed significantly from baseline to 1 month
      after acute respiratory infection.

PMID- 29462108
TI  - Disulfiram attenuates morphine or methadone withdrawal syndrome in mice.
AB  - Taking opioids is often accompanied by the development of dependence.
      Unfortunately, treatment of opioid dependence is difficult, particularly because
      of codependence - for example, on alcohol or other drugs of abuse. In the
      presented study, we analyzed the potential influence of disulfiram, a drug used
      to aid the management of alcoholism, on opioid abstinence syndrome, which occurs
      as a result of opioid withdrawal. Opioid dependence in mice was induced by
      subcutaneous administration of either morphine or methadone at a dose of 48 mg/kg
      for 10 consecutive days. To trigger a withdrawal syndrome, the opioid receptor
      antagonist, naloxone, was administered at a dose of 1 mg/kg (subcutaneous), and
      the severity of withdrawal signs was assessed individually. Interruption of
      chronic treatment with morphine or methadone by naloxone has led to the
      occurrence of opioid abstinence signs such as jumping, paw tremor, wet-dog
      shakes, diarrhea, teeth chattering, ptosis, and piloerection. Importantly,
      pretreatment with disulfiram (25, 50, and 100 mg/kg) reduced the intensity of
      withdrawal signs induced by naloxone in morphine or methadone-treated mice. These
      findings show the effectiveness of disulfiram in reducing opioid abstinence
      signs.

PMID- 29462109
TI  - Effects of the active constituents of Crocus sativus L. crocins and their
      combination with memantine on recognition memory in rats.
AB  - Crocus sativus L., is a plant cultivated in many countries of the world. Crocins
      are among the active constituents of C. sativus and their implication in
      cognition has been proposed. The present study was designed to investigate in the
      rat the effects of crocins on distinct recognition memory components (encoding,
      storage and retrieval). Subsequently, the potential use of crocins as adjunctive
      agents for the treatment of memory disorders was examined. Thus, the effects
      exerted by a combination of subthreshold doses of crocins and memantine on
      recognition memory were evaluated. To assess the effects of compounds on memory,
      the novel object-recognition task (NORT) was used. In a preliminary study, the
      influence of the retention time (the delay between the two trials) on the
      performance of rats was assessed. Rats' recognition memory abilities remained
      intact up to 6 h, but were extinguished when a delay of 24 h was utilized.
      Crocins, at any dose tested (5, 15, and 30 mg/kg), did not affect rats'
      performance, whereas administration of higher doses (15 and 30 mg/kg) reversed
      delay-dependent deficits in the NORT. The combination of subthreshold doses of
      crocins (5 mg/kg) and memantine (3 mg/kg) did not influence the performance, but
      counteracted delay-dependent deficits in the NORT. These findings suggest that
      crocins counteract natural forgetting and may modulate different aspects of
      recognition memory, and that the combined use of crocins and memantine might
      represent a novel strategy to treat memory disorders.

PMID- 29462110
TI  - Strain differences in the susceptibility to the gut-brain axis and
      neurobehavioural alterations induced by maternal immune activation in mice.
AB  - There is a growing realization that the severity of the core symptoms of autism
      spectrum disorders and schizophrenia is associated with gastrointestinal
      dysfunction. Nonetheless, the mechanisms underlying such comorbidities remain
      unknown. Several genetic and environmental factors have been linked to a higher
      susceptibility to neurodevelopmental abnormalities. The maternal immune
      activation (MIA) rodent model is a valuable tool for elucidating the basis of
      this interaction. We induced MIA with polyinosinic-polycytidylic acid (poly I:C)
      at gestational day 12.5 and assessed behavioural, physiological and molecular
      aspects relevant to the gut-brain axis in the offspring of an outbred (NIH Swiss)
      and an inbred (C57BL6/J) mouse strain. Our results showed that the specific MIA
      protocol employed induces social deficits in both strains. However, alterations
      in anxiety and depression-like behaviours were more pronounced in NIH Swiss mice.
      These strain-specific behavioural effects in the NIH Swiss mice were associated
      with marked changes in important components of gut-brain axis communication: the
      endocrine response to stress and gut permeability. In addition, MIA-induced
      changes in vasopressin receptor 1a mRNA expression in the hypothalamus were
      observed in NIH Swiss mice only. Taken together, these data suggest that genetic
      background is a critical factor in susceptibility to the gut-brain axis effects
      induced by MIA.

PMID- 29462111
TI  - Medication overuse headache following repeated morphine, but not [INCREMENT]9
      tetrahydrocannabinol administration in the female rat.
AB  - The potential of [INCREMENT]-tetrahydrocannabinol (THC) as a treatment for
      migraine depends on antinociceptive efficacy with repeated administration.
      Although morphine has good antinociceptive efficacy, repeated administration
      causes medication overuse headache (MOH) - a condition in which the
      intensity/frequency of migraine increases. The present study compared the effect
      of repeated morphine or THC administration on the magnitude and duration of
      migraine-like pain induced by a microinjection of allyl isothiocyanate (AITC)
      onto the dura mater of female rats. Acute administration of THC or morphine
      prevented AITC-induced depression of wheel running. This antinociception was
      maintained in rats treated repeatedly with THC, but not following repeated
      administration of morphine. Moreover, repeated morphine, but not THC
      administration, extended the duration of AITC-induced depression of wheel
      running. These data indicate that tolerance and MOH develop rapidly to morphine
      administration. The lack of tolerance and MOH to THC indicates that THC may be an
      especially effective long-term treatment against migraine.

PMID- 29462112
TI  - Microinjection of the mGluR2/3 agonist, LY379268, into the nucleus accumbens
      attenuates extinction latencies and the reinstatement of morphine-induced
      conditioned place preference in rats.
AB  - Previous studies indicate that metabotropic glutamate receptor type 2/3
      (mGluR2/3) has a key role in the rewarding properties of morphine-induced
      conditioning place preference (CPP). Group II mGluR2/3 agonists are offered as a
      drug addiction treatment. The nucleus accumbens (NAc), which is one of the
      important areas involved in the reward circuitry, also expresses these receptors.
      In this study, we evaluated the effects of mGluR2/3 agonist, LY379268, on the
      extinction and reinstatement of morphine-induced CPP, following its
      microinjection into the NAc. Adult male Wistar rats (220-250 g) were implanted
      bilaterally by two separate cannulae into the NAc. After the acquisition of
      morphine CPP, different doses of LY379268 (0.3, 1 and 3 ug/0.5 MUl saline) were
      microinjected into the NAc every day during the extinction period and, in a
      different set of experiments, on the reinstatement test day, 60 min before the
      infusion of a priming dose of morphine (1 mg/kg; subcutaneous). Thereafter, the
      animals were tested for place preference by the Ethovision software. The intra
      accumbal injection of the mGluR2/3 agonist, LY379268, significantly decreased the
      extinction latencies and reinstatement of morphine-induced CPP at higher doses.
      It seems that the NAc might be a functional region for mGluR2/3 to play a
      regulatory role for decreasing drug-seeking behavior in rats. Furthermore, it can
      be said that mGluR2/3 agonists have a potential role in the treatment of drug
      seeking behaviors.

PMID- 29462113
TI  - Use of open and endovascular surgical techniques to manage vascular injuries in
      the trauma setting: A review of the American Association for the Surgery of
      Trauma PROspective Observational Vascular Injury Trial registry.
AB  - BACKGROUND: Vascular trauma data have been submitted to the American Association
      for the Surgery of Trauma PROspective Observational Vascular Injury Trial
      (PROOVIT) database since 2013. We present data to describe current use of
      endovascular surgery in vascular trauma. METHODS: Registry data from March 2013
      to December 2016 were reviewed. All trauma patients who had an injury to a named
      artery, except the forearm and lower leg, were included. Arteries were grouped
      into anatomic regions and by compressible and noncompressible region for
      analysis. This review focused on patients with noncompressible transection,
      partial transection, or flow-limiting defect injuries. Bivariate and multivariate
      analyses were used to assess the relationships between study variables. RESULTS:
      One thousand one hundred forty-three patients from 22 institutions were included.
      Median age was 32 years (interquartile range, 23-48) and 76% (n = 871) were male.
      Mechanisms of injury were 49% (n = 561) blunt, 41% (n = 464) penetrating, and
      1.8% (n = 21) of mixed aetiology. Gunshot wounds accounted for 73% (n = 341) of
      all penetrating injuries. Endovascular techniques were used least often in limb
      trauma and most commonly in patients with blunt injuries to more than one region.
      Penetrating wounds to any region were preferentially treated with open surgery
      (74%, n = 341/459). The most common indication for endovascular treatment was
      blunt noncompressible torso injuries. These patients had higher Injury Severity
      Scores and longer associated hospital stays, but required less packed red blood
      cells, and had lower in hospital mortality than those treated with open surgery.
      On multivariate analysis, admission low hemoglobin concentration and abdominal
      injury were independent predictors of mortality. CONCLUSION: Our review of
      PROOVIT registry data demonstrates a high utilization of endovascular therapy
      among severely injured blunt trauma patients primarily with noncompressible torso
      hemorrhage. This is associated with a decreased need for blood transfusion and
      improved survival despite longer length of stay. LEVEL OF EVIDENCE:
      Therapeutic/care management, level III.

PMID- 29462115
TI  - The pitfalls of resuscitative endovascular balloon occlusion of the aorta: Risk
      factors and mitigation strategies: Erratum.

PMID- 29462114
TI  - Clinical relevance of a p value: Does tranexamic acid save lives after trauma or
      postpartum hemorrhage?

PMID- 29462116
TI  - Featured Articles for CME Credit March 2018.

PMID- 29462120
TI  - Understanding the Epidemiology of Pediatric Supracondylar Humeral Fractures in
      the United States: Identifying Opportunities for Intervention.
AB  - BACKGROUND: Supracondylar humeral fractures (SCHF) are the most common elbow
      fractures in children. The epidemiology of these injuries in the United States is
      described. METHODS: The Nationwide Emergency Department Sample database was
      queried for all children (age, below 18 y) with SCHF treated in the emergency
      department (ED) from 2006 to 2011, and weighted estimates were extracted.
      RESULTS: A total of 63,348 ED visits for SCHF were identified. The weighted
      estimate of ED visits remained stable over the study period, ranging from 60.3 to
      71.8 per 100,000 children annually. There was no significant difference in
      fracture rate (52% male) by sex. The mean age of closed injury was 5.5+/-3.1
      years, with 53.6% of fractures occurring in children 3 to 6 years. Open injuries
      accounted for 1.0% of fractures. Children with open injuries were significantly
      older (mean, 9.1+/-4.4 y; P<0.0001) and more often male (OR, 1.43; P<0.001).
      Neurovascular injury occurred in significantly older children (mean, 7.6+/-3.1 y;
      P<0.0001) and was documented in 11.4% of open fractures and 3.6% of operative
      fractures. Although the South had the greatest number of total SCHF-related ED
      visits, children in the West had significantly more SCHF-related ED visits per
      100,000 children annually (77.9) than all other regions (P<0.05). Average
      fracture rates were approximately 60% higher in April to September than October
      to March (P<0.001). Mean total charges for patients treated and discharged from
      the ED were $2965, compared with $17,865 in children admitted for surgery
      (P<0.05). Mean charges were significantly higher in the West compared with all
      other regions (P<0.0001). CONCLUSIONS: The incidence of pediatric SCHF-related ED
      visits remained stable from 2006 to 2011 and occurred most frequently in children
      aged 3 to 6 years. Open injuries are rare and are more likely to occur in older
      boys. There are significant differences in the injury rates and charges across
      geographic regions, identifying opportunities for injury prevention, cost
      reduction, and value improvement. The indications for operative management should
      be clearly delineated given the high cost of surgical treatment. LEVEL OF
      EVIDENCE: Therapeutic Level IV.

PMID- 29462119
TI  - Comparison of Methicillin-resistant Versus Susceptible Staphylococcus aureus
      Pediatric Osteomyelitis.
AB  - BACKGROUND: The incidence of methicillin-resistant Staphylococcus aureus (MRSA)
      pediatric osteomyelitis has risen and been associated with a more severe clinical
      course than methicillin-susceptible Staphylococcus aureus (MSSA) infections.
      National databases have been underutilized to describe these trends. We compared
      demographics, clinical course, and outcomes for patients with MRSA versus MSSA
      osteomyelitis. METHODS: We queried the 2009 and 2012 Healthcare Cost and
      Utilization Project Kids Inpatient Database for discharge records with diagnosis
      codes for osteomyelitis and S. aureus. We explored demographics predicting MRSA
      and evaluated MRSA versus MSSA as predictors of clinical outcomes including
      surgery, sepsis, thrombophlebitis, length of stay, and total charges. RESULTS: A
      total of 4214 discharge records were included. Of those, 2602 (61.7%) had MSSA
      and 1612 (38.3%) had MRSA infections. Patients at Southern and Midwestern
      hospitals were more likely to have MRSA than those at Northeastern hospitals.
      Medicaid patients' odds of MRSA were higher than those with private insurance,
      and black patients were more likely to have MRSA compared with white patients.
      MRSA patients were more likely to undergo multiple surgeries compared with MSSA
      patients and were more likely to have complications including severe sepsis,
      thrombophlebitis, and pulmonary embolism. Patients with MRSA had longer lengths
      of stay than those with MSSA and higher total charges after controlling for
      length of stay. CONCLUSION: Review of a national database demonstrates MRSA is
      more prevalent in the South and Midwest regions and among black patients. MRSA
      patients have more surgeries, complications, and longer lengths of stay. LEVEL OF
      EVIDENCE: Level III.

PMID- 29462121
TI  - Patient Mortality in Geriatric Distal Femur Fractures.
AB  - OBJECTIVES: To estimate 1-year mortality rates in elderly patients who undergo
      operative treatment for distal femur fractures and identify potential risk
      factors for mortality. DESIGN: Retrospective chart review. SETTING: Level 1 and
      Level 2 trauma centers. PATIENTS/PARTICIPANTS: Two hundred eighty-three elderly
      patients (average age 76.0 years +/- 9.8) who sustained distal femur fractures
      between 2002 and 2012. INTERVENTION: Fracture fixation of the distal femur. MAIN
      OUTCOME MEASURE: Survival up to 1 year after surgery. RESULTS: The 1-year
      mortality rate for distal femur fractures in elderly patients was 13.4%. There
      were no statistically significant differences in overall mortality between native
      bone and periprosthetic fractures, intramedullary nail or open reduction internal
      fixation, or across Orthopaedic Trauma Association fracture classifications.
      Overall patient mortality was significantly higher at 30 days (P = 0.036), 6
      months (P = 0.019), and 1 year (P = 0.018), when surgery occurred more than 2
      days from the injury. Mean Charlson Comorbidity Index scores were significantly
      lower in survivors versus nonsurvivors at all time intervals (30 days, P = 0.023;
      6 months, P = 0.001 and 1 year P <= 0.001). A time to surgery of more than 2
      days, regardless of baseline illness, did not result in improved survivability at
      1 year. CONCLUSIONS: Overall mortality for distal femur fractures was 13.4% in
      the elderly population. A surgical treatment more than 2 days after injury was
      associated with increased patient mortality. LEVEL OF EVIDENCE: Prognostic Level
      III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 29462122
TI  - Risk of Hip Arthroplasty After Open Reduction Internal Fixation of a Fracture of
      the Acetabulum: A Matched Cohort Study.
AB  - OBJECTIVES: To determine what proportion of operatively treated acetabular
      fracture patients proceeded to total hip arthroplasty (THA), over what time
      period, and quantify the influence of patient, provider, and surgical factors on
      rates of THA. DESIGN: Retrospective matched cohort prognostic study using
      administrative data. SETTING: This study used the large population database of
      Ontario (population 13,125,000 in 2010), Canada. PARTICIPANTS: Patients who
      underwent open reduction internal fixation (ORIF) of an acetabulum fracture
      between 1996 and 2010 in the province of Ontario were identified from
      administrative health databases. METHOD: Each patient was matched to 4
      individuals from the general population according to age, sex, income, and
      urban/rural residence. The rates of THA at 2, 5, and 10 years were compared using
      time-to-event analysis. The influence of patient, provider, and surgical factors
      on the risk of eventual THA was examined using a Cox model. INTERVENTION: The
      primary intervention was ORIF of the acetabulum. MAIN OUTCOME MEASUREMENT: The
      primary outcome measurement was THA. RESULTS: A total of 1725 eligible patients
      were identified and were matched to 6900 controls. Among cases, there was a 13.9%
      (N = 240) rate of hip arthroplasty after a median of 6.25 (interquartile range
      3.5-10.1) years, compared with 0.6% (N = 38) among matched controls (relative
      risk = 25.26). The greatest difference in risk of eventually undergoing a THA was
      in the first 10 years, after which time the risk in the group that had undergone
      ORIF acetabulum trended down toward that of the control group. Among surgical
      patients, risk factors for eventual hip arthroplasty included older age [hazard
      ratio (HR) 1.035 (1.027, 1.044); P < 0.0001]; female sex [HR 1.65 (1.257, 2.165);
      P = 0.0003]. Higher surgeon volume revealed a 2.6% decreased risk of arthroplasty
      for each acetabulum ORIF performed above 10 per year [HR 0.974 (0.960, 0.989); P
      = 0.0007]. CONCLUSION: Patients who underwent acetabulum fracture ORIF had a 25
      times higher prevalence of hip arthroplasty compared with matched controls. THA
      rate was greater in women, older patients, and patients whom had ORIF performed
      by low-volume surgeons. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 29462124
TI  - Impact of United States Preventive Services Task Force Recommendations on
      Utilization of Prostate-specific Antigen Screening in Medicare Beneficiaries.
AB  - BACKGROUND: Previous studies assessing the impact of United States Preventive
      Services Task Force (USPSTF) recommendations on utilization of prostate-specific
      antigen (PSA) screening have not investigated longer-term impacts of 2008
      recommendations nor have they investigated the impact of 2012 recommendations in
      the Medicare population. This study aimed to evaluate change in utilization of
      PSA screening, post-2008 and 2012 USPSTF recommendations, and assessed trends and
      determinants of receipt of PSA screening in the Medicare population. METHODS:
      This retrospective study of male Medicare beneficiaries utilized Medicare Current
      Beneficiary Survey data and linked administrative claims from 2006 to 2013.
      Beneficiaries aged >=65 years, with continuous enrollment in parts A and B for
      each year they were surveyed were included in the study. Beneficiaries with self
      reported/claims-based diagnosis of prostate cancer were excluded. The primary
      outcome was receipt of PSA screening. Other measures included age groups (65 to
      74 and >=75), time periods (pre-2008/post-2008 and 2012 recommendations), and
      sociodemographic variables. RESULTS: The study cohort consisted of 11,028
      beneficiaries, who were predominantly white (87.56%), married (69.25%), and
      unemployed (84.4%); 52.21% beneficiaries were aged >=75. Declining utilization
      trends for PSA screening were observed in men aged >=75 after 2008
      recommendations and in both age groups after 2012 recommendations. The odds of
      receiving PSA screening declined by 17% in men aged >=75 after 2008
      recommendations and by 29% in men aged >=65 after 2012 recommendations.
      CONCLUSIONS: The 2008 and 2012 USPSTF recommendations against PSA screening were
      associated with declines in utilization of PSA screening during the study period.
      USPSTF recommendations play a significant role in affecting utilization patterns
      of health services.

PMID- 29462123
TI  - Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma: Findings of
      the Phase 1b KEYNOTE-028 Study.
AB  - OBJECTIVES: Treatment options for patients with unresectable or metastatic
      salivary gland carcinoma (SGC) are limited. Safety and efficacy of pembrolizumab
      for SGC expressing programmed death ligand 1 (PD-L1) were explored. MATERIALS AND
      METHODS: A cohort of patients with advanced, PD-L1-positive SGC was enrolled in
      the nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with
      PD-L1-positive advanced solid tumors (KEYNOTE-028; NCT02054806). Key inclusion
      criteria included recurrent or metastatic disease, failure of prior systemic
      therapy, and PD-L1 expression on >=1% of tumor or stroma cells (per a prototype
      immunohistochemistry assay). Patients received pembrolizumab 10 mg/kg every 2
      weeks for >=2 years or until confirmed disease progression or unacceptable
      toxicity. Primary end point was objective response rate per Response Evaluation
      Criteria in Solid Tumors version 1.1 by investigator review. RESULTS: Twenty-six
      patients with PD-L1-positive SGC were enrolled and treated; median age was 57
      years, 88% were men, and 74% had received prior therapy for recurrent/metastatic
      disease. Confirmed objective response rate after median follow-up of 20 months
      was 12% (95% confidence interval, 2%-30%), with 3 patients achieving partial
      response; there were no complete responses. Median duration of response was 4
      months (range, 4 to 21 mo). Treatment-related adverse events occurred in 22
      patients (85%), resulting in discontinuation in 2 patients and death in 1
      (interstitial lung disease); those occurring in >=15% of patients were diarrhea,
      decreased appetite, pruritus, and fatigue. CONCLUSIONS: Pembrolizumab
      demonstrated promising antitumor activity and a manageable safety profile in
      patients with advanced, PD-L1-positive SGC.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- 29462125
TI  - Increased Expression of TREK-1 K+ Channel in the Dorsal Root Ganglion of Rats
      with Detrusor Overactivity After Partial Bladder Outlet Obstruction.
AB  - BACKGROUND Changes in expression and activity of ion channels are important
      pathophysiological mechanisms underlying detrusor overactivity (DO) in partial
      bladder outlet obstruction (PBOO). The objective of this study was to examine the
      expression of TREK-1 channel in the bladder and central nervous system of DO
      rats. MATERIAL AND METHODS Thirty Sprague-Dawley rats were subjected to PBOO
      operations and those displaying non-voiding contractions (NVCs) in cystometry
      were classified as DO. Sham-operated rats without NVCs in cystometry served as
      controls. The expression and distribution of TREK-1 in the bladder, spinal cord,
      and dorsal root ganglion (DRG) were detected by real time-PCR, western blot, and
      immunohistochemistry. RESULTS TREK-1 channel expression in the DRG was
      significantly increased at the mRNA level (11.20+/-3.762 vs. 3.209+/-1.505,
      P<0.01) and protein level (2.195+/-0.058 vs. 1.713+/-0.066, P<0.01) in DO rats as
      compared to control rats. However, the expression of TREK-1 mRNA in the bladder
      (1.380+/-0.810 vs. 4.206+/-3.827, P>0.05) and spinal cord (0.764+/-0.357 vs.
      0.696+/-0.188, P>0.05) was comparable between the 2 groups. Immunohistochemistry
      showed enhanced immunoreactive signals of TREK-1 channel in the DRG, but not in
      the spinal cord and bladder. CONCLUSIONS TREK-1 channel was upregulated in the
      DRG of DO rats after chronic PBOO, which might suppress neuronal excitability and
      play a protective role in bladder overactivity in PBOO.

PMID- 29462126
TI  - Plasticity and intratumoural heterogeneity of cell surface antigen expression in
      breast cancer.
AB  - Background:The intratumoural heterogeneity, often driven by epithelial-to
      mesenchymal transition (EMT), significantly contributes to chemoresistance and
      disease progression in adenocarcinomas.Methods:We introduced a high-throughput
      screening platform to identify surface antigens that associate with epithelial
      mesenchymal plasticity in well-defined pairs of epithelial cell lines and their
      mesenchymal counterparts. Using multicolour flow cytometry, we then analysed the
      expression of 10 most robustly changed antigens and identified a 10-molecule
      surface signature, in pan-cytokeratin-positive/EpCAM-positive and -negative
      fractions of dissociated breast tumours.Results:We found that surface CD9, CD29,
      CD49c, and integrin beta5 are lost in breast cancer cells that underwent EMT in
      vivo. The tetraspanin family member CD9 was concordantly downregulated both in
      vitro and in vivo and associated with epithelial phenotype and favourable
      prognosis.Conclusions:We propose that overall landscape of 10-molecule surface
      signature expression reflects the epithelial-mesenchymal plasticity in breast
      cancer.

PMID- 29462127
TI  - Ex vivo metabolic fingerprinting identifies biomarkers predictive of prostate
      cancer recurrence following radical prostatectomy.
AB  - This corrects the article DOI: 10.1038/bjc.2017.346.

PMID- 29462128
TI  - miR-146a-5p mediates epithelial-mesenchymal transition of oesophageal squamous
      cell carcinoma via targeting Notch2.
AB  - This corrects the article DOI: 10.1038/bjc.2016.367.

PMID- 29462129
TI  - Family history of cancer and the risk of childhood solid tumours: a Norwegian
      nationwide register-based cohort study.
AB  - This corrects the article DOI: 10.1038/bjc.2017.85.

PMID- 29462130
TI  - Risk of cancer in patients with epistaxis and haemoptysis.
AB  - This corrects the article DOI: 10.1038/bjc.2017.85.

PMID- 29462131
TI  - Pathological complete response and prognosis after neoadjuvant chemotherapy for
      HER2-positive breast cancers before and after trastuzumab era: results from a
      real-life cohort.
AB  - This corrects the article DOI: 10.1038/bjc.2017.85.

PMID- 29462132
TI  - Development of a prognostic scoring system for patients with advanced cancer
      enrolled in immune checkpoint inhibitor phase 1 clinical trials.
AB  - This corrects the article DOI: 10.1038/bjc.2017.85.

PMID- 29462133
TI  - Clinical characteristics and epidemiology of intestinal tapeworm infections over
      the last decade in Tokyo, Japan: A retrospective review.
AB  - BACKGROUND: Tapeworm (cestode) infections occur worldwide even in developed
      countries and globalization has further complicated the epidemiology of such
      infections. Nonetheless, recent epidemiological data on cestode infections are
      limited. Our objectives were to elucidate the clinical characteristics and
      epidemiology of diphyllobothriosis and taeniosis in Tokyo, Japan.
      METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively reviewed 24 cases of human
      intestinal cestode infection from January 2006 to December 2015 at a tertiary
      referral hospital in Tokyo, Japan. The patients included were diagnosed with
      cestode infection based on morphological and/or molecular identification of
      expelled proglottids and/or eggs and treated in our hospital. Fifteen and 9
      patients were diagnosed with diphyllobothriosis and taeniosis, respectively. The
      median patient age was 31 years (interquartile range [IQR]: 26-42 years), and 13
      (54%) were male. Most of the patients (91.7%) were Japanese. All patients were
      successfully treated with praziquantel without recurrence. Diphyllobothriosis was
      caused by Diphyllobothrium nihonkaiense in all patients. Taeniosis was due to
      infection of Taenia saginata in 8 [88.9%] patients and T. asiatica in 1 [11.1%]
      patient. All patients with taeniosis were infected outside Japan, as opposed to
      those with diphyllobothriosis, which were domestic. The source locations of
      taeniosis were mostly in developing regions. The median duration of the stay of
      the patients with taeniosis at the respective source location was 1 month (IQR: 1
      8). CONCLUSIONS/SIGNIFICANCE: The cestode infection, especially with D.
      nihonkaiense, has frequently occurred, even in Japanese cities, thereby
      implicating the probable increase in the prevalence of diphyllobothriosis among
      travelers, as the number of travelers is expected to increase owing to the Tokyo
      Olympics/Paralympics in 2020. In addition, medical practitioners should be aware
      of the importance of providing advice to travelers to endemic countries of
      taeniosis, including the potential risks of infection and preventive methods for
      these infections.

PMID- 29462134
TI  - An insight into the salivary gland and fat body transcriptome of Panstrongylus
      lignarius (Hemiptera: Heteroptera), the main vector of Chagas disease in Peru.
AB  - Triatomines are hematophagous arthropod vectors of Trypanosoma cruzi, the
      causative agent of Chagas Disease. Panstrongylus lignarius, also known as
      Panstrongylus herreri, is considered one of the most versatile triatomines
      because it can parasitize different hosts, it is found in different habitats and
      countries, it has sylvatic, peridomestic and domestic behavior and it is a very
      important vector of Chagas disease, especially in Peru. Molecules produced and
      secreted by salivary glands and fat body are considered of important adaptational
      value for triatomines because, among other functions, they subvert the host
      haemostatic, inflammatory and immune systems and detoxify or protect them against
      environmental aggressors. In this context, the elucidation of the molecules
      produced by these tissues is highly valuable to understanding the ability of this
      species to adapt and transmit pathogens. Here, we use high-throughput sequencing
      techniques to assemble and describe the coding sequences resulting from the
      transcriptome of the fat body and salivary glands of P. lignarius. The final
      assembly of both transcriptomes together resulted in a total of 11,507 coding
      sequences (CDS), which were mapped from a total of 164,676,091 reads. The CDS
      were subdivided according to their 10 folds overexpression on salivary glands
      (513 CDS) or fat body (2073 CDS). Among the families of proteins found in the
      salivary glands, lipocalins were the most abundant. Other ubiquitous families of
      proteins present in other sialomes were also present in P. lignarius, including
      serine protease inhibitors, apyrase and antigen-5. The unique transcriptome of
      fat body showed proteins related to the metabolic function of this organ.
      Remarkably, nearly 20% of all reads mapped to transcripts coded by Triatoma
      virus. The data presented in this study improve the understanding on triatomines'
      salivary glands and fat body function and reveal important molecules used in the
      interplay between vectors and vertebrate hosts.

PMID- 29462136
TI  - DNA methylation profiling of genomic DNA isolated from urine in diabetic chronic
      kidney disease: A pilot study.
AB  - AIM: To characterise the genomic DNA (gDNA) yield from urine and quality of
      derived methylation data generated from the widely used Illuminia Infinium
      MethylationEPIC (HM850K) platform and compare this with buffy coat samples.
      BACKGROUND: DNA methylation is the most widely studied epigenetic mark and
      variations in DNA methylation profile have been implicated in diabetes which
      affects approximately 415 million people worldwide. METHODS: QIAamp Viral RNA
      Mini Kit and QIAamp DNA micro kit were used to extract DNA from frozen and fresh
      urine samples as well as increasing volumes of fresh urine. Matched buffy coats
      to the frozen urine were also obtained and DNA was extracted from the buffy coats
      using the QIAamp DNA Mini Kit. Genomic DNA of greater concentration than 20MUg/ml
      were used for methylation analysis using the HM850K array. RESULTS: Irrespective
      of extraction technique or the use of fresh versus frozen urine samples, limited
      genomic DNA was obtained using a starting sample volume of 5ml (0-0.86MUg/mL). In
      order to optimize the yield, we increased starting volumes to 50ml fresh urine,
      which yielded only 0-9.66MUg/mL A different kit, QIAamp DNA Micro Kit, was
      trialled in six fresh urine samples and ten frozen urine samples with inadequate
      DNA yields from 0-17.7MUg/mL and 0-1.6MUg/mL respectively. Sufficient genomic DNA
      was obtained from only 4 of the initial 41 frozen urine samples (10%) for DNA
      methylation profiling. In comparison, all four buffy coat samples (100%) provided
      sufficient genomic DNA. CONCLUSION: High quality data can be obtained provided a
      sufficient yield of genomic DNA is isolated. Despite optimizing various
      extraction methodologies, the modest amount of genomic DNA derived from urine,
      may limit the generalisability of this approach for the identification of DNA
      methylation biomarkers of chronic diabetic kidney disease.

PMID- 29462135
TI  - Accomplishing the genotype-specific serodiagnosis of single and dual Trypanosoma
      cruzi infections by flow cytometry Chagas-Flow ATE-IgG2a.
AB  - The methods currently available for genotype-specific diagnosis of T. cruzi
      infection still present relevant limitations, especially to identify mixed
      infection. In the present investigation, we have evaluated the performance of
      Chagas-Flow ATE-IgG2a test for early and late differential diagnosis of single
      and dual genotype-specific T. cruzi infections. Serum samples from Swiss mice at
      early and late stages of T. cruzi infection were assayed in parallel batches for
      genotype-specific diagnosis of single (TcI, TcVI or TcII) and dual (TcI+TcVI,
      TcVI+TcII or TcII+TcI) infections. The intrinsic reactivity to TcI, TcVI and TcII
      target antigens, including amastigote (AI/AVI/AII), trypomastigote-(TI/TVI/TII)
      and epimastigote (EI/EVI/EII), at specific reverse of serum dilutions (500 to
      64,000), was employed to provide reliable decision-trees for "early" vs "late",
      "single vs "dual" and "genotype-specific" serology. The results demonstrated that
      selective set of attributes "EII 500/EI 2,000/AII 500" were able to provide high
      quality accuracy (81%) to segregate early and late stages of T. cruzi infection.
      The sets "TI 2,000/AI 1,000/EII 1,000" and "TI 8,000/AII 32,000" presented
      expressive scores to discriminate single from dual T. cruzi infections at early
      (85%) and late stages (84%), respectively. Moreover, the attributes "TI 4,000/TVI
      500/TII 1,000", "TI 16,000/EI 2,000/EII 2,000/AI 500/TVI 500" showed good
      performance for genotype-specific diagnosis at early stage of single (72%) and
      dual (80%) T. cruzi infections, respectively. In addition, the attributes "TI
      4,000/AII 1,000/EVI 1,000", "TI 64,000/AVI 500/AI 2,000/AII 1,000/EII 4,000"
      showed moderate performance for genotype-specific diagnosis at late stage of
      single (69%) and dual (76%) T. cruzi infections, respectively. The sets of
      decision-trees were assembled to construct a sequential algorithm with expressive
      accuracy (81%) for serological diagnosis of T. cruzi infection. These findings
      engender new perspectives for the application of Chagas-Flow ATE-IgG2a method for
      genotype-specific diagnosis in humans, with relevant contributions for
      epidemiological surveys as well as clinical and post-therapeutic monitoring of
      Chagas disease.

PMID- 29462137
TI  - The premammillary nucleus of the hypothalamus is not necessary for photoperiodic
      timekeeping in female turkeys (Meleagris gallopavo).
AB  - In birds, seasonal reproduction is regulated by day length, with long days in the
      spring activating the hypothalamic-pituitary-gonadal axis and reproductive
      behaviors. The photoreceptors mediating this process remain unknown, but
      recently, the premammillary nucleus (PMM) of the hypothalamus has been implicated
      as the site of photoperiodic signaling in turkeys. We performed electrolytic
      lesions of the PMM to elucidate its role in the photoactivation and maintenance
      of egg production in female turkeys. Our results show that ablation of the PMM
      does not alter the normal lay cycle. No differences were found between lesioned
      birds and sham controls in the latency to lay following photostimulation, nor in
      subsequent egg production over a period of 29 weeks. No differences in the
      incidence of gonadal regression were found, indicating that the PMM is not
      essential for the termination of breeding. We conclude that any role of the PMM
      in photoperiodic regulation, if it exists, is redundant with other components of
      the system.

PMID- 29462138
TI  - The 2014-2015 Ebola virus disease outbreak and primary healthcare delivery in
      Liberia: Time-series analyses for 2010-2016.
AB  - BACKGROUND: The aim of this study is to estimate the immediate and lasting
      effects of the 2014-2015 Ebola virus disease (EVD) outbreak on public-sector
      primary healthcare delivery in Liberia using 7 years of comprehensive routine
      health information system data. METHODS AND FINDINGS: We analyzed 10 key primary
      healthcare indicators before, during, and after the EVD outbreak using 31,836
      facility-month service outputs from 1 January 2010 to 31 December 2016 across a
      census of 379 public-sector health facilities in Liberia (excluding Montserrado
      County). All indicators had statistically significant decreases during the first
      4 months of the EVD outbreak, with all indicators having their lowest raw mean
      outputs in August 2014. Decreases in outputs comparing the end of the initial EVD
      period (September 2014) to May 2014 (pre-EVD) ranged in magnitude from a 67.3%
      decrease in measles vaccinations (95% CI: -77.9%, -56.8%, p < 0.001) and a 61.4%
      decrease in artemisinin-based combination therapy (ACT) treatments for malaria
      (95% CI: -69.0%, -53.8%, p < 0.001) to a 35.2% decrease in first antenatal care
      (ANC) visits (95% CI: -45.8%, -24.7%, p < 0.001) and a 38.5% decrease in
      medroxyprogesterone acetate doses (95% CI: -47.6%, -29.5%, p < 0.001). Following
      the nadir of system outputs in August 2014, all indicators showed statistically
      significant increases from October 2014 to December 2014. All indicators had
      significant positive trends during the post-EVD period, with every system output
      exceeding pre-Ebola forecasted trends for 3 consecutive months by November 2016.
      Health system outputs lost during and after the EVD outbreak were large and
      sustained for most indicators. Prior to exceeding pre-EVD forecasted trends for 3
      months, we estimate statistically significant cumulative losses of -776,110
      clinic visits (95% CI: -1,480,896, -101,357, p = 0.030); -24,449 bacille Calmette
      Guerin vaccinations (95% CI: -45,947, -2,020, p = 0.032); -9,129 measles
      vaccinations (95% CI: -12,312, -5,659, p < 0.001); -17,191 postnatal care (PNC)
      visits within 6 weeks of birth (95% CI: -28,344, -5,775, p = 0.002); and -101,857
      ACT malaria treatments (95% CI: -205,839, -2,139, p = 0.044) due to the EVD
      outbreak. Other outputs showed statistically significant cumulative losses only
      through December 2014, including losses of -12,941 first pentavalent vaccinations
      (95% CI: -20,309, -5,527, p = 0.002); -5,122 institutional births (95% CI: 
      8,767, -1,234, p = 0.003); and -45,024 acute respiratory infections treated (95%
      CI: -66,185, -24,019, p < 0.001). Compared to pre-EVD forecasted trends,
      medroxyprogesterone acetate doses and first ANC visits did not show statistically
      significant net losses. ACT treatment for malaria was the only indicator with an
      estimated net increase in system outputs through December 2016, showing an excess
      of +78,583 outputs (95% CI: -309,417, +450,661, p = 0.634) compared to pre-EVD
      forecasted trends, although this increase was not statistically significant.
      However, comparing December 2013 to December 2017, ACT malaria cases have
      increased 49.2% (95% CI: 33.9%, 64.5%, p < 0.001). Compared to pre-EVD forecasted
      trends, there remains a statistically significant loss of -15,144 PNC visits
      within 6 weeks (95% CI: -29,453, -787, p = 0.040) through December 2016.
      CONCLUSIONS: The Liberian public-sector primary healthcare system has made
      strides towards recovery from the 2014-2015 EVD outbreak. All primary healthcare
      indicators tracked have recovered to pre-EVD levels as of November 2016. Yet, for
      most indicators, it took more than 1 year to recover to pre-EVD levels. During
      this time, large losses of essential primary healthcare services occurred
      compared to what would have been expected had the EVD outbreak not occurred. The
      disruption of malaria case management during the EVD outbreak may have resulted
      in increased malaria cases. Large and sustained investments in public-sector
      primary care health system strengthening are urgently needed for EVD-affected
      countries.

PMID- 29462139
TI  - The COP9 Signalosome regulates seed germination by facilitating protein
      degradation of RGL2 and ABI5.
AB  - The control of seed germination and seed dormancy are critical for the successful
      propagation of plant species, and are important agricultural traits. Seed
      germination is tightly controlled by the balance of gibberellin (GA) and abscisic
      acid (ABA), and is influenced by environmental factors. The COP9 Signalosome
      (CSN) is a conserved multi-subunit protein complex that is best known as a
      regulator of the Cullin-RING family of ubiquitin E3 ligases (CRLs). Multiple
      viable mutants of the CSN showed poor germination, except for csn5b-1. Detailed
      analyses showed that csn1-10 has a stronger seed dormancy, while csn5a-1 mutants
      exhibit retarded seed germination in addition to hyperdormancy. Both csn5a-1 and
      csn1-10 plants show defects in the timely removal of the germination inhibitors:
      RGL2, a repressor of GA signaling, and ABI5, an effector of ABA responses. We
      provide genetic evidence to demonstrate that the germination phenotype of csn1-10
      is caused by over-accumulation of RGL2, a substrate of the SCF (CRL1) ubiquitin
      E3 ligase, while the csn5a-1 phenotype is caused by over-accumulation of RGL2 as
      well as ABI5. The genetic data are consistent with the hypothesis that CSN5A
      regulates ABI5 by a mechanism that may not involve CSN1. Transcriptome analyses
      suggest that CSN1 has a more prominent role than CSN5A during seed maturation,
      but CSN5A plays a more important role than CSN1 during seed germination, further
      supporting the functional distinction of these two CSN genes. Our study
      delineates the molecular targets of the CSN complex in seed germination, and
      reveals that CSN5 has additional functions in regulating ABI5, thus the ABA
      signaling pathway.

PMID- 29462140
TI  - DNA damage as a consequence of NLR activation.
AB  - DNA damage observed during plant immune responses is reported to be an intrinsic
      component of plant immunity. However, other immune responses may suppress DNA
      damage to maintain host genome integrity. Here, we show that immunity-related DNA
      damage can be abrogated by preventing cell death triggered by Nucleotide-binding,
      Leucine-rich-repeat immune Receptors (NLRs). SNI1 (suppressor of npr1-1,
      inducible 1), a subunit of the structural maintenance of chromosome (SMC) 5/6
      complex, was reported to be a negative regulator of systemic acquired resistance
      (SAR) and to be necessary for controlling DNA damage. We find that cell death and
      DNA damage in sni1 loss-of-function mutants are prevented by mutations in the NLR
      signaling component EDS1. Similar to sni1, elevated DNA damage is seen in other
      autoimmune mutants with cell death lesions, including camta3, pub13 and vad1, but
      not in dnd1, an autoimmune mutant with no visible cell death. We find that as in
      sni1, DNA damage in camta3 is EDS1-dependent, but that it is also NLR-dependent.
      Using the NLR RPM1 as a model, we also show that extensive DNA damage is observed
      when an NLR is directly triggered by effectors. We also find that the expression
      of DNA damage repair (DDR) genes in mutants with cell death lesions is down
      regulated, suggesting that degraded DNA that accumulates during cell death is a
      result of cellular dismantling and is not sensed as damaged DNA that calls for
      repair. Our observations also indicate that SNI1 is not directly involved in SAR
      or DNA damage accumulation.

PMID- 29462141
TI  - The Mediator co-activator complex regulates Ty1 retromobility by controlling the
      balance between Ty1i and Ty1 promoters.
AB  - The Ty1 retrotransposons present in the genome of Saccharomyces cerevisiae belong
      to the large class of mobile genetic elements that replicate via an RNA
      intermediary and constitute a significant portion of most eukaryotic genomes. The
      retromobility of Ty1 is regulated by numerous host factors, including several
      subunits of the Mediator transcriptional co-activator complex. In spite of its
      known function in the nucleus, previous studies have implicated Mediator in the
      regulation of post-translational steps in Ty1 retromobility. To resolve this
      paradox, we systematically examined the effects of deleting non-essential
      Mediator subunits on the frequency of Ty1 retromobility and levels of
      retromobility intermediates. Our findings reveal that loss of distinct Mediator
      subunits alters Ty1 retromobility positively or negatively over a >10,000-fold
      range by regulating the ratio of an internal transcript, Ty1i, to the genomic Ty1
      transcript. Ty1i RNA encodes a dominant negative inhibitor of Ty1 retromobility
      that blocks virus-like particle maturation and cDNA synthesis. These results
      resolve the conundrum of Mediator exerting sweeping control of Ty1 retromobility
      with only minor effects on the levels of Ty1 genomic RNA and the capsid protein,
      Gag. Since the majority of characterized intrinsic and extrinsic regulators of
      Ty1 retromobility do not appear to effect genomic Ty1 RNA levels, Mediator could
      play a central role in integrating signals that influence Ty1i expression to
      modulate retromobility.

PMID- 29462143
TI  - Prescriptive variability of drugs by general practitioners.
AB  - Prescription drug spending is growing faster than any other sector of healthcare.
      However, very little is known about patterns of prescribing and cost of
      prescribing between general practices. In this study, we examined variation in
      prescription rates and prescription costs through time for 55 GP surgeries in
      Northern Ireland Western Health and Social Care Trust. Temporal changes in
      variability of prescribing rates and costs were assessed using the Mann-Kendall
      test. Outlier practices contributing to between practice variation in prescribing
      rates were identified with the interquartile range outlier detection method. The
      relationship between rates and cost of prescribing was explored with Spearman's
      statistics. The differences in variability and mean number of prescribing rates
      associated with the practice setting and socioeconomic deprivation were tested
      using t-test and F-test respectively. The largest between-practice difference in
      prescribing rates was observed for Apr-Jun 2015, with the number of prescriptions
      ranging from 3.34 to 8.36 per patient. We showed that practices with outlier
      prescribing rates greatly contributed to between-practice variability. The
      largest difference in prescribing costs was reported for Apr-Jun 2014, with the
      prescription cost per patient ranging from L26.4 to L64.5. In addition, the
      temporal changes in variability of prescribing rates and costs were shown to
      undergo an upward trend. We demonstrated that practice setting and socio-economic
      deprivation accounted for some of the between-practice variation in prescribing.
      Rural practices had higher between practice variability than urban practices at
      all time points. Practices situated in more deprived areas had higher prescribing
      rates but lower variability than those located in less deprived areas. Further
      analysis is recommended to assess if variation in prescribing can be explained by
      demographic characteristics of patient population and practice features.
      Identification of other factors contributing to prescribing variability can help
      us better address potential inappropriateness of prescribing.

PMID- 29462142
TI  - RNF8 and SCML2 cooperate to regulate ubiquitination and H3K27 acetylation for
      escape gene activation on the sex chromosomes.
AB  - The sex chromosomes are enriched with germline genes that are activated during
      the late stages of spermatogenesis. Due to meiotic sex chromosome inactivation
      (MSCI), these sex chromosome-linked genes must escape silencing for activation in
      spermatids, thereby ensuring their functions for male reproduction. RNF8, a DNA
      damage response protein, and SCML2, a germline-specific Polycomb protein, are two
      major, known regulators of this process. Here, we show that RNF8 and SCML2
      cooperate to regulate ubiquitination during meiosis, an early step to establish
      active histone modifications for subsequent gene activation. Double mutants of
      Rnf8 and Scml2 revealed that RNF8-dependent monoubiquitination of histone H2A at
      Lysine 119 (H2AK119ub) is deubiquitinated by SCML2, demonstrating interplay
      between RNF8 and SCML2 in ubiquitin regulation. Additionally, we identify
      distinct functions of RNF8 and SCML2 in the regulation of ubiquitination: SCML2
      deubiquitinates RNF8-independent H2AK119ub but does not deubiquitinate RNF8
      dependent polyubiquitination. RNF8-dependent polyubiquitination is required for
      the establishment of H3K27 acetylation, a marker of active enhancers, while
      persistent H2AK119ub inhibits establishment of H3K27 acetylation. Following the
      deposition of H3K27 acetylation, H3K4 dimethylation is established as an active
      mark on poised promoters. Together, we propose a model whereby regulation of
      ubiquitin leads to the organization of poised enhancers and promoters during
      meiosis, which induce subsequent gene activation from the otherwise silent sex
      chromosomes in postmeiotic spermatids.

PMID- 29462144
TI  - Perceptions on evaluative and formative functions of external supervision of
      Rwandan primary healthcare facilities: A qualitative study.
AB  - BACKGROUND: External supervision of primary healthcare facilities in low- and
      middle-income countries often has a managerial main purpose in which the role of
      support for professional development is unclear. AIM: To explore how Rwandan
      primary healthcare supervisors and providers (supervisees) perceive evaluative
      and formative functions of external supervision. DESIGN: Qualitative, exploratory
      study. DATA: Focus group discussions: three with supervisors, three with
      providers, and one mixed (n = 31). Findings were discussed with individual and
      groups of supervisors and providers. RESULTS: Evaluative activities occupied
      providers' understanding of supervision, including checking, correcting, marking
      and performance-based financing. These were presented as sources of motivation,
      that in self-determination theory indicate introjected regulation. Supervisors
      preferred to highlight their role in formative supervision, which may mask their
      own and providers' uncontested accounts that systematic performance evaluations
      predominated supervisors' work. Providers strongly requested larger focus on
      formative and supportive functions, voiced as well by most supervisors. Impact of
      performance evaluation on motivation and professional development is discussed.
      CONCLUSION: While external supervisors intended to support providers'
      professional development, our findings indicate serious problems with this in a
      context of frequent evaluations and performance marking. Separating the role of
      supporter and evaluator does not appear as the simple solution. If external
      supervision is to improve health care services, it is essential that supervisors
      and health centre managers are competent to support providers in a way that
      transparently accounts for various performance pressures. This includes delivery
      of proper formative supervision with useful feedback, maintaining an effective
      supervisory relationship, as well as ensuring providers are aware of the purpose
      and content of evaluative and formative supervision functions.

PMID- 29462145
TI  - Videourodynamic findings of lower urinary tract dysfunctions in men with
      persistent storage lower urinary tract symptoms after medical treatment.
AB  - OBJECTIVE: To analyze the underlying lower urinary tract dysfunctions by video
      urodynamic studies in men who have persistent storage symptoms after initial drug
      therapy for lower urinary tract symptoms (LUTS) suggestive of benign prostatic
      hyperplasia (BPH). METHODS: The medical records of 614 men >=40 years of age with
      LUTS and an International Prostate Symptom Score of >=8 were retrospectively
      analyzed. All patients had persistent storage symptoms after medical treatment
      for at least 6 months. A video-urodynamic study was done to investigate the
      underlying bladder or bladder outlet dysfunction. Predictors of bladder outlet
      obstruction (BOO) by baseline urine flow metrics and prostate parameters were
      investigated. RESULTS: The final results revealed bladder neck dysfunction (BND)
      in 137/614 (22.3%), benign prostatic obstruction (BPO) in 246/614 (40.1%),
      detrusor overactivity (DO) in 193/614 (31.4%), and DO with detrusor underactivity
      (DO+DU) in 38/614 (6.2%) patients. Among the patients, 221/281 (78.6%) with a
      total prostatic volume (TPV) >=40 ml had BOO, including 43/281 (15.3%) with BND
      and 178/281 (63.3%) with BPO. If we combined TPV >=40 ml and Qmax <12 ml/s as
      predictors of BOO, BOO was found in 176/215 (81.8%) patients including 34/215
      (15.8%) with BND and 142/215 (66.0%) with BPO. BOO was also found in 48.8% of men
      with a TPV <40ml, and in 36.3% of men with TPV< 40 ml and Qmax >= 12 ml/s. In 102
      men with TPV <40 ml and Qmax >=12 ml/s, 64 (62.7%) had DO. CONCLUSION: BOO,
      including BND and BPO, comprise 62.4% (383/614) of men with persistent storage
      symptoms after initial medical treatment for LUTS/BPH. In men who have persistent
      storage symptoms after medical treatment for LUTS/BPH, BOO should be carefully
      investigated and appropriate management being given to improve LUTS.

PMID- 29462146
TI  - Prospective evaluation of accuracy and clinical utility of the Dual Path Platform
      (DPP) assay for the point-of-care diagnosis of leptospirosis in hospitalized
      patients.
AB  - Early detection of leptospirosis with field-ready diagnostics may improve
      clinical management and mitigate outbreaks. We previously validated the point-of
      care Dual Path Platform (DPP) for leptospirosis with sera in the laboratory. This
      prospective study compares the diagnostic accuracy and clinical utility of the
      DPP using finger stick blood (FSB) against the serum DPP, venous whole blood
      (VWB) DPP, IgM-ELISA, and clinical impression. We sequentially enrolled 98
      patients hospitalized for acute febrile illnesses, of which we confirmed 32 by
      leptospirosis reference tests. Among syndromes consistent with classic
      leptospirosis, the FSB DPP showed similar sensitivity and specificity (Se 93% and
      Sp 80%), and positive and negative predictive values (PPV 74% and NPV 95%), to
      VWB DPP (Se 96%, Sp 75%, PPV 68%, and NPV 97%), serum DPP (Se 85%, Sp 87%, PPV
      79%, and NPV 91%) and IgM-ELISA (Se 81%, Sp 100%, PPV 100%, and NPV 90%). The FSB
      DPP provided a favorable likelihood ratio profile (positive LR 4.73, negative LR
      0.09) in comparison to other assays and clinical impression alone. Additionally,
      we identified four of five leptospirosis-associated meningitis patients by whole
      blood DPP, none of which clinicians suspected. This demonstrates potential for
      the DPP in routine detection of this less common syndrome. The FSB DPP
      demonstrated similar discrimination for severe human leptospirosis compared with
      serum assays, and it is a simpler option for diagnosing leptospirosis. Its
      performance in other epidemiological settings and geographic regions, and for
      detecting atypical presentations, demands further evaluation.

PMID- 29462147
TI  - Exploiting the geometry of the solution space to reduce sensitivity to neuromotor
      noise.
AB  - Throwing is a uniquely human skill that requires a high degree of coordination to
      successfully hit a target. Timing of ball release appears crucial as previous
      studies report required timing accuracies as short as 1-2ms, which however appear
      physiologically challenging. This study mathematically and experimentally
      demonstrates that humans can overcome these seemingly stringent timing
      requirements by shaping their hand trajectories to create extended timing
      windows, where ball releases achieve target hits despite temporal imprecision.
      Subjects practiced four task variations in a virtual environment, each with a
      distinct geometry of the solution space and different demands for timing. Model
      based analyses of arm trajectories revealed that subjects first decreased timing
      error, followed by lengthening timing windows in their hand trajectories. This
      pattern was invariant across solution spaces, except for a control case. Hence,
      the exquisite skill that humans evolved for throwing is achieved by developing
      strategies that are less sensitive to temporal variability arising from
      neuromotor noise. This analysis also provides an explanation why coaches
      emphasize the "follow-through" in many ball sports.

PMID- 29462148
TI  - Vocal development through morphological computation.
AB  - The vocal behavior of infants changes dramatically during early life. Whether or
      not such a change results from the growth of the body during development-as
      opposed to solely neural changes-has rarely been investigated. In this study of
      vocal development in marmoset monkeys, we tested the putative causal relationship
      between bodily growth and vocal development. During the first two months of life,
      the spontaneous vocalizations of marmosets undergo (1) a gradual disappearance of
      context-inappropriate call types and (2) an elongation in the duration of context
      appropriate contact calls. We hypothesized that both changes are the natural
      consequences of lung growth and do not require any changes at the neural level.
      To test this idea, we first present a central pattern generator model of marmoset
      vocal production to demonstrate that lung growth can affect the temporal and
      oscillatory dynamics of neural circuits via sensory feedback from the lungs. Lung
      growth qualitatively shifted vocal behavior in the direction observed in real
      marmoset monkey vocal development. We then empirically tested this hypothesis by
      placing the marmoset infants in a helium-oxygen (heliox) environment in which air
      is much lighter. This simulated a reversal in development by decreasing the
      effort required to respire, thus increasing the respiration rate (as though the
      lungs were smaller). The heliox manipulation increased the proportions of
      inappropriate call types and decreased the duration of contact calls, consistent
      with a brief reversal of vocal development. These results suggest that bodily
      growth alone can play a major role in shaping the development of vocal behavior.

PMID- 29462149
TI  - The INO80 chromatin remodeler sustains metabolic stability by promoting TOR
      signaling and regulating histone acetylation.
AB  - Chromatin remodeling complexes are essential for gene expression programs that
      coordinate cell function with metabolic status. However, how these remodelers are
      integrated in metabolic stability pathways is not well known. Here, we report an
      expansive genetic screen with chromatin remodelers and metabolic regulators in
      Saccharomyces cerevisiae. We found that, unlike the SWR1 remodeler, the INO80
      chromatin remodeling complex is composed of multiple distinct functional subunit
      modules. We identified a strikingly divergent genetic signature for the Ies6
      subunit module that links the INO80 complex to metabolic homeostasis. In
      particular, mitochondrial maintenance is disrupted in ies6 mutants. INO80 is also
      needed to communicate TORC1-mediated signaling to chromatin, as ino80 mutants
      exhibit defective transcriptional profiles and altered histone acetylation of
      TORC1-responsive genes. Furthermore, comparative analysis reveals subunits of
      INO80 and mTORC1 have high co-occurrence of alterations in human cancers.
      Collectively, these results demonstrate that the INO80 complex is a central
      component of metabolic homeostasis that influences histone acetylation and may
      contribute to disease when disrupted.

PMID- 29462150
TI  - Host plant forensics and olfactory-based detection in Afro-tropical mosquito
      disease vectors.
AB  - The global spread of vector-borne diseases remains a worrying public health
      threat, raising the need for development of new combat strategies for vector
      control. Knowledge of vector ecology can be exploited in this regard, including
      plant feeding; a critical resource that mosquitoes of both sexes rely on for
      survival and other metabolic processes. However, the identity of plant species
      mosquitoes feed on in nature remains largely unknown. By testing the hypothesis
      about selectivity in plant feeding, we employed a DNA-based approach targeting
      trnH-psbA and matK genes and identified host plants of field-collected Afro
      tropical mosquito vectors of dengue, Rift Valley fever and malaria being among
      the most important mosquito-borne diseases in East Africa. These included three
      plant species for Aedes aegypti (dengue), two for both Aedes mcintoshi and Aedes
      ochraceus (Rift Valley fever) and five for Anopheles gambiae (malaria). Since
      plant feeding is mediated by olfactory cues, we further sought to identify
      specific odor signatures that may modulate host plant location. Using coupled gas
      chromatography (GC)-electroantennographic detection, GC/mass spectrometry and
      electroantennogram analyses, we identified a total of 21 antennally-active
      components variably detected by Ae. aegypti, Ae. mcintoshi and An. gambiae from
      their respective host plants. Whereas Ae. aegypti predominantly detected
      benzenoids, Ae. mcintoshi detected mainly aldehydes while An. gambiae detected
      sesquiterpenes and alkenes. Interestingly, the monoterpenes beta-myrcene and (E)
      beta-ocimene were consistently detected by all the mosquito species and present
      in all the identified host plants, suggesting that they may serve as signature
      cues in plant location. This study highlights the utility of molecular approaches
      in identifying specific vector-plant associations, which can be exploited in
      maximizing control strategies such as such as attractive toxic sugar bait and
      odor-bait technology.

PMID- 29462151
TI  - The self-organization of plant microtubules inside the cell volume yields their
      cortical localization, stable alignment, and sensitivity to external cues.
AB  - Many cell functions rely on the ability of microtubules to self-organize as
      complex networks. In plants, cortical microtubules are essential to determine
      cell shape as they guide the deposition of cellulose microfibrils, and thus
      control mechanical anisotropy of the cell wall. Here we analyze how, in turn,
      cell shape may influence microtubule behavior. Building upon previous models that
      confined microtubules to the cell surface, we introduce an agent model of
      microtubules enclosed in a three-dimensional volume. We show that the microtubule
      network has spontaneous aligned configurations that could explain many
      experimental observations without resorting to specific regulation. In
      particular, we find that the preferred cortical localization of microtubules
      emerges from directional persistence of the microtubules, and their interactions
      with each other and with the stiff wall. We also identify microtubule parameters
      that seem relatively insensitive to cell shape, such as length or number. In
      contrast, microtubule array anisotropy depends on local curvature of the cell
      surface and global orientation follows robustly the longest axis of the cell.
      Lastly, we find that geometric cues may be overcome, as the network is capable of
      reorienting toward weak external directional cues. Altogether our simulations
      show that the microtubule network is a good transducer of weak external polarity,
      while at the same time, easily reaching stable global configurations.

PMID- 29462152
TI  - Distance, accessibility and costs. Decision-making during childbirth in rural
      Sierra Leone: A qualitative study.
AB  - BACKGROUND: Sierra Leone has one of the highest maternal mortality ratios in the
      world. Efforts to reduce maternal mortality have included initiatives to
      encourage more women to deliver at health facilities. Despite the introduction of
      the free health care initiative for pregnant women, many women still continue to
      deliver at home, with few having access to a skilled birth attendant. In
      addition, inequalities between rural and urban areas in accessing and utilising
      health facilities persist. Further insight into how and why women make decisions
      around childbirth will help guide future plans and initiatives in improving
      maternal health in Sierra Leone. The objective of this study was to explore the
      perceptions and decision-making processes of women and their communities during
      childbirth in rural Sierra Leone. METHODS AND FINDINGS: Data were collected
      through seven focus group discussions and 22 in-depth interviews with recently
      pregnant women and their community members in two rural villages. Data were
      analysed using systematic text condensation. Findings revealed that decision
      making processes during childbirth are dynamic, intricate and need to be
      understood within the broader social context that they take place. Factors such
      as distance and lack of transport, perceived negative behaviour of hospital
      staff, direct and indirect financial obstacles, as well as the position of women
      in society all interact and influence how and what decisions are made.
      CONCLUSIONS: Pregnant women face multiple interacting vulnerabilities that
      influence their healthcare-seeking decisions during pregnancy and childbirth.
      Future initiatives to improve access and utilisation of safe healthcare services
      for pregnant women need to be based on adequate knowledge of structural
      constraints and health inequities that affect women in rural Sierra Leone.

PMID- 29462153
TI  - Design of synthetic bacterial communities for predictable plant phenotypes.
AB  - Specific members of complex microbiota can influence host phenotypes, depending
      on both the abiotic environment and the presence of other microorganisms.
      Therefore, it is challenging to define bacterial combinations that have
      predictable host phenotypic outputs. We demonstrate that plant-bacterium binary
      association assays inform the design of small synthetic communities with
      predictable phenotypes in the host. Specifically, we constructed synthetic
      communities that modified phosphate accumulation in the shoot and induced
      phosphate starvation-responsive genes in a predictable fashion. We found that
      bacterial colonization of the plant is not a predictor of the plant phenotypes we
      analyzed. Finally, we demonstrated that characterizing a subset of all possible
      bacterial synthetic communities is sufficient to predict the outcome of untested
      bacterial consortia. Our results demonstrate that it is possible to infer causal
      relationships between microbiota membership and host phenotypes and to use these
      inferences to rationally design novel communities.

PMID- 29462154
TI  - Functional characterization and genomic studies of a novel murine submandibular
      gland epithelial cell line.
AB  - A better understanding of the normal and diseased biology of salivary glands (SG)
      has been hampered, in part, due to difficulties in cultivating and maintaining
      salivary epithelial cells. Towards this end, we have generated a mouse salivary
      gland epithelial cell (mSGc) culture system that is well-suited for the molecular
      characterization of SG cells and their differentiation program. We demonstrate
      that mSGc can be maintained for multiple passages without a loss of proliferation
      potential, readily form 3D-spheroids and importantly express a panel of well
      established salivary gland epithelial cell markers. Moreover, mSGc 3D-spheroids
      also exhibit functional maturation as evident by robust agonist-induced
      intracellular calcium signaling. Finally, transcriptomic characterization of mSGc
      by RNA-seq and hierarchical clustering analysis with adult organ RNA-seq datasets
      reveal that mSGc retain most of the molecular attributes of adult mouse salivary
      gland. This well-characterized mouse salivary gland cell line will fill a
      critical void in the field by offering a valuable resource to examine various
      mechanistic aspects of mouse salivary gland biology.

PMID- 29462155
TI  - Rifampicin versus streptomycin for brucellosis treatment in humans: A meta
      analysis of randomized controlled trials.
AB  - Brucellosis is a zoonotic disease with a high morbidity in developing countries,
      but there the optimal treatment is not yet determined. Therefore, the development
      of a simple and effective treatment is important. The aim of this study was to
      summarize the available evidences and compare rifampicin with streptomycin in
      human brucellosis with doxycycline as background regimen. We systematically
      searched PubMed, EmBase, and the Cochrane Library from their inception up through
      December 2016. We included studies with a randomized controlled design that
      evaluated the effect of streptomycin compared with rifampicin in human
      brucellosis patients who received doxycycline therapy as background regimen. The
      overall failure and relapse were summarized using random-effects model. Our meta
      analysis included 1,383 patients with brucellosis from 14 trials. We found that
      patients who received rifampicin therapy had a higher risk of overall failure
      (RR: 2.36; 95% CI: 1.72-3.23; P<0.001) and relapse (RR: 2.74; 95% CI: 1.80-4.19;
      P<0.001) compared with streptomycin. Results of the sensitivity analysis were
      consistent with the overall analysis. Subgroup analysis indicated that mean age
      of the patients and percentage of male participants might influence the treatment
      effects. Furthermore, no publication bias was detected. The findings of this
      study indicated that rifampicin therapy significantly increased the risk of
      overall failure and relapse compared with streptomycin. Hence, it can be
      recommended to patients with human brucellosis receiving streptomycin therapy.

PMID- 29462156
TI  - Preferences for HIV test characteristics among young, Black Men Who Have Sex With
      Men (MSM) and transgender women: Implications for consistent HIV testing.
AB  - BACKGROUND: Promoting consistent HIV testing is critical among young, Black Men
      Who Have Sex With Men (MSM) and transgender women who are overrepresented among
      new HIV cases in the United States. New HIV test options are available, including
      mobile unit testing, one-minute testing, at home or self-testing and couples HIV
      testing and counseling (CHTC). In the context of these newer options, the
      objective of this study was to explore whether and how preferences for specific
      characteristics of the tests acted as barriers to and/or facilitators of testing
      in general and consistent testing specifically among young Black MSM and
      transgender women aged 16 to 29. METHODS: We conducted 30 qualitative, semi
      structured, in-depth interviews with young, Black, gay, bisexual or MSM and
      transgender women in the New York City metropolitan area to identify preferences
      for specific HIV tests and aspects of HIV testing options. Participants were
      primarily recruited from online and mobile sites, followed by community-based,
      face-to-face recruitment strategies to specifically reach younger participants.
      Thematic coding was utilized to analyze the qualitative data based on a grounded
      theoretical approach. RESULTS: We identified how past experiences, perceived test
      characteristics (e.g., accuracy, cost, etc.) and beliefs about the "fit" between
      the individual, and the test relate to preferred testing methods and consistent
      testing. Three major themes emerged as important to preferences for HIV testing
      methods: the perceived accuracy of the test method, venue characteristics, and
      lack of knowledge or experience with the newer testing options, including self
      testing and CHTC. CONCLUSIONS: These findings suggest that increasing awareness
      of and access to newer HIV testing options (e.g., free or reduced price on home
      or self-tests or CHTC available at all testing venues) is critical if these new
      options are to facilitate increased levels of consistent testing among young,
      Black MSM and transgender women. Addressing perceptions of test accuracy and
      supporting front line staff in creating welcoming and safe testing environments
      may be key intervention targets. Connecting young Black MSM and transgender women
      to the best test option, given preferences for specific characteristics, may
      support more and more consistent HIV testing.

PMID- 29462157
TI  - A mouse model study of toxicity and biodistribution of a replication defective
      adenovirus serotype 5 virus with its genome engineered to contain a decoy hyper
      binding site to sequester and suppress oncogenic HMGA1 as a new cancer treatment
      therapy.
AB  - The HGMA1 architectural transcription factor is highly overexpressed in many
      human cancers. Because HMGA1 is a hub for regulation of many oncogenes, its
      overexpression in cancer plays a central role in cancer progression and therefore
      HMGA1 is gaining increasing attention as a target for development of therapeutic
      approaches to suppress either its expression or action in cancer cells. We have
      developed the strategy of introducing decoy hyper binding sites for HMGA1 into
      the nucleus of cancer cells with the goal of competetively sequestering
      overexpressed HMGA1 and thus suppressing its oncogenic action. Towards achieving
      this goal, we have introduced an HMGA1 decoy hyper binding site composed of six
      copies of a high affinity HMGA1 binding site into the genome of the replication
      defective adenovirus serotype 5 genome and shown that the engineered virus
      effectively reduces the viability of human pancreatic and cancer cells. Here we
      report the first pre-clinical measures of toxicity and biodistribution of the
      engineered virus in C57BL/6J Black 6 mice. The immune response to exposure of the
      engineered virus was determined by assaying the serum levels of key cytokines, IL
      6 and TNF-alpha. Toxicity due to exposure to the virus was determined by
      measuring the serum levels of the liver enzymes aspartate aminotransferase and
      alanine aminotransferase. Biodistribution was measured following direct injection
      into the pancreas or liver by quantifying viral loads in the pancreas, liver,
      spleen and brain.

PMID- 29462158
TI  - Docosahexaenoic acid for reading, working memory and behavior in UK children aged
      7-9: A randomized controlled trial for replication (the DOLAB II study).
AB  - BACKGROUND: Omega-3 fatty acids are central to brain-development of children.
      Evidence from clinical trials and systematic reviews demonstrates the potential
      of long-chain Omega-3 supplementation for learning and behavior. However,
      findings are inconclusive and in need of robust replication studies since such
      work is lacking. OBJECTIVES: Replication of the 2012 DOLAB 1 study findings that
      a dietary supplementation with the long-chain omega-3 docosahexaenoic acid (DHA)
      had beneficial effects on the reading, working memory, and behavior of healthy
      schoolchildren. DESIGN: Parallel group, fixed-dose, randomized (minimization, 30%
      random element), double-blind, placebo-controlled trial (RCT). SETTING:
      Mainstream primary schools (n = 84) from five counties in the UK in 2012-2015.
      PARTICIPANTS: Healthy children aged 7-9 underperforming in reading (<20th
      centile). 1230 invited, 376 met study criteria. INTERVENTION: 600 mg/day DHA
      (from algal oil), placebo: taste/color matched corn/soybean oil; for 16 weeks.
      MAIN OUTCOME MEASURES: Age-standardized measures of reading, working memory, and
      behavior, parent-rated and as secondary outcome teacher-rated. RESULTS: 376
      children were randomized. Reading, working memory, and behavior change scores
      showed no consistent differences between intervention and placebo group. Some
      behavioral subscales showed minor group differences. CONCLUSIONS: This RCT did
      not replicate results of the earlier DOLAB 1 study on the effectiveness of
      nutritional supplementation with DHA for learning and behavior. Possible reasons
      are discussed, particularly regarding the replication of complex interventions.
      TRIAL REGISTRATION AND PROTOCOL: www.controlled-trials.com (ISRCTN48803273) and
      protocols.io (https://dx.doi.org/10.17504/protocols.io.k8kczuw).

PMID- 29462159
TI  - Factors associated with occasional and recurrent falls in Mexican community
      dwelling older people.
AB  - Falls are a frequent event among older adults that can cause wounds, disability,
      psychological disorders, and premature death. Although the large number of
      existing studies on the issue, few have been conducted in middle- and low-income
      countries. The objective of the present study is to identify the
      sociodemographic, medical, and functional performance factors associated with
      occasional and recurrent falls in Mexican older adults dwelling in community.
      Cross-sectional analysis of 9 598 adults >=60 years old who participated in the
      fourth round (2015) of the Mexican Health and Aging Study. Bivariate tests were
      performed to evaluate the differences between covariates by distinct fall groups
      (no falls, occasional falls, and recurrent falls). Multiple logistic regressions
      with unadjusted and adjusted models were estimated. Approximately 46% of older
      adults had had at least one fall during the previous two years (one fall 16% and
      recurrent falls 30%). Occasional falls were only associated with being a woman;
      in addition to the sex, recurrent falls were strongly associated with advanced
      age, rural residence, bad and very bad self-perception of health status, activity
      limiting pain, urinary incontinence, depression, arthritis, limitations in basic
      activities of daily living, and limitations in advanced activities of daily
      living. Falls, primarily recurrent falls, deserve to be addressed through
      multifactorial strategies that include different areas of intervention.

PMID- 29462160
TI  - Identifying potential maternal genes of Bombyx mori using digital gene expression
      profiling.
AB  - Maternal genes present in mature oocytes play a crucial role in the early
      development of silkworm. Although maternal genes have been widely studied in many
      other species, there has been limited research in Bombyx mori. High-throughput
      next generation sequencing provides a practical method for gene discovery on a
      genome-wide level. Herein, a transcriptome study was used to identify maternal
      related genes from silkworm eggs. Unfertilized eggs from five different stages of
      early development were used to detect the changing situation of gene expression.
      The expressed genes showed different patterns over time. Seventy-six maternal
      genes were annotated according to homology analysis with Drosophila melanogaster.
      More than half of the differentially expressed maternal genes fell into four
      expression patterns, while the expression patterns showed a downward trend over
      time. The functional annotation of these material genes was mainly related to
      transcription factor activity, growth factor activity, nucleic acid binding, RNA
      binding, ATP binding, and ion binding. Additionally, twenty-two gene clusters
      including maternal genes were identified from 18 scaffolds. Altogether, we
      plotted a profile for the maternal genes of Bombyx mori using a digital gene
      expression profiling method. This will provide the basis for maternal-specific
      signature research and improve the understanding of the early development of
      silkworm.

PMID- 29462161
TI  - Lipoproteins comprise at least 10 different classes in rats, each of which
      contains a unique set of proteins as the primary component.
AB  - Although lipoproteins are conventionally separated into a few classes using
      density gradient centrifugation, there may be a much higher number of physical
      classes that differ in origin or phase. Comprehensive knowledge of the classes of
      lipoproteins is rather limited, which hinders both the study of their functions
      and the identification of the primary causes of related diseases. This study aims
      to determine the number of classes of lipoproteins that can be practically
      distinguishable and identify the differences between them. We separated rat serum
      samples by gel filtration. The elution was continuously monitored for
      triglyceride (TG), cholesterol, and protein, and fractionated for further SDS
      PAGE and immunological detection of apoprotein A-I (ApoA1) and apoprotein B
      (ApoB). The elution patterns were analyzed using a parsimonious method, i.e., the
      estimation of the least number of classes. Ten classes were recognized that
      contained different amounts of TG and cholesterol, as well as a unique protein
      content. Each of the classes contained much more protein than that observed
      previously, especially in low-density lipoproteins (LDL) classes. In particular,
      two major antiproteases formed complexes with specific classes of LDL; because
      these classes exclusively carry cholesterol and antiproteases, they may lead to
      the progression of atheroma by supplying materials that enlarge fatty streaks and
      protecting thrombi from enzymatic digestion. The separated classes may have
      specific biological functions. The attribution of protein species to certain
      classes will help understand the functions. A distinction among lipoprotein
      classes may provide important information in the field of vascular pathology.

PMID- 29462162
TI  - Vasomotor and physical menopausal symptoms are associated with sleep quality.
AB  - BACKGROUND: Sleep disturbance is one of the common complaints in menopause. This
      study investigated the relationship between menopausal symptoms and sleep quality
      in middle-aged women. METHOD: This cross-sectional observational study involved
      634 women aged 44-56 years attending a healthcare center at Kangbuk Samsung
      Hospitals. Sleep quality was measured using the Pittsburgh Sleep Quality Index
      (PSQI).Multiple linear regression analysis was performed to assess the
      associations between Menopause-specific Quality of Life (MENQOL) scores and PSQI
      scores and Menopause-specific Quality of Life (MENQOL)scores. RESULTS: The mean
      PSQI score was 3.6+/-2.3, and the rates of poor sleep quality(PSQI score > 5) in
      premenopausal, perimenopausal, and postmenopausal women were 14.4%, 18.2%, and
      30.2%, respectively. Total PSQI score, specifically the sleep latency, habitual
      sleep efficiency and sleep disturbances scores, were significantly increased in
      postmenopausal women. Multiple linear regression analysis adjusted for age, BMI,
      hypertension, diabetes, smoking, marital status, family income, education,
      employment status, parity, physical activity, depression symptoms, perceived
      stress and menopausal status showed that higher PSQI score was positively
      correlated with higher vasomotor(beta = 0.240, P = 0.020)and physical(beta =
      0.572, P<0.001) scores. CONCLUSIONS: Vasomotor and physical menopause symptoms
      was related to poor sleep quality. Effective management strategies aimed at
      reducing menopausal symptoms may improve sleep quality among women around the
      time of menopause.

PMID- 29462163
TI  - Social-emotional competence and early adolescents' peer acceptance in school:
      Examining the role of afternoon cortisol.
AB  - The present study investigated the role of afternoon cortisol in social-emotional
      competence and peer acceptance in early adolescence. To date, research on basal
      cortisol activity and social development in childhood and adolescence has
      predominately focused on understanding maladjustment and dysfunction in
      development. The degree to which basal cortisol is also involved in positive
      adjustment and social functioning remains largely unexplored. A total of 154
      early adolescents (46% female; Mean age = 11.26; SD = .65) from diverse ethnic
      backgrounds provided self-reports of perspective taking, peer reports of
      acceptance by classmates, peer reports of prosocial behaviors, and saliva samples
      to assess basal cortisol. As expected and in alignment with previous research,
      afternoon cortisol, perspective taking, prosocial behaviors, and peer acceptance
      were all positively correlated. Path analyses followed by bootstrapping analyses
      revealed that the direct path from higher afternoon cortisol to higher levels of
      prosocial behavior was fully mediated by perspective taking skills. The direct
      path from higher afternoon cortisol to peer acceptance was fully mediated by
      perspective taking skills and prosocial behavior. The findings are discussed
      within the broader context of previous research on cortisol and social adjustment
      in childhood and early adolescence. The practical relevance of the findings is
      considered.

PMID- 29462164
TI  - Phylogeography and DNA-based species delimitation provide insight into the
      taxonomy of the polymorphic rose chafer Protaetia (Potosia) cuprea species
      complex (Coleoptera: Scarabaeidae: Cetoniinae) in the Western Palearctic.
AB  - The development of modern methods of species delimitation, unified under the
      "integrated taxonomy" approach, allows a critical examination and re-evaluation
      of complex taxonomic groups. The rose chafer Protaetia (Potosia) cuprea is a
      highly polymorphic species group with a large distribution range. Despite its
      overall commonness, its taxonomy is unclear and subject to conflicting
      hypotheses, most of which largely fail to account for its evolutionary history.
      Based on the sequences of two mitochondrial markers from 65 individuals collected
      across the species range, and a detailed analysis of morphological characters
      including a geometric morphometry approach, we infer the evolutionary history and
      phylogeography of the P. cuprea species complex. Our results demonstrate the
      existence of three separate lineages in the Western Palearctic region, presumably
      with a species status. However, these lineages are in conflict with current
      taxonomic concepts. None of the 29 analyzed morphological characters commonly
      used in the taxonomy of this group proved to be unambiguously species- or
      subspecies- specific. The geometric morphometry analysis reveals a large overlap
      in the shape of the analyzed structures (pronotum, meso-metaventral projection,
      elytra and aedeagus), failing to identify either the genetically detected clades
      or the classical species entities. Our results question the monophyly of P.
      cuprea in regard to P. cuprina, as well as the species status of P. metallica. On
      the other hand, we found support for the species status of the Sicilian P.
      hypocrita. Collectively, our findings provide a new and original insight into the
      taxonomy and phylogeny of the P. cuprea species complex. At the same time, the
      results represent the first attempt to elucidate the phylogeography of these
      polymorphic beetles.

PMID- 29462165
TI  - Thromboelastometry profile in critically ill patients: A single-center,
      retrospective, observational study.
AB  - BACKGROUND: Transfusion therapy is associated with increased morbidity, mortality
      and costs. Conventional coagulation tests (CCT) are weak bleeding predictors,
      poorly reflecting coagulation in vivo. Thromboelastometry (ROTEM) provides early
      identification of coagulation disorders and can guide transfusion therapy by
      goals, reducing blood components transfusion. OBJECTIVE: The aim of this study is
      to describe coagulation profile of critically ill patients using ROTEM and
      evaluate the association between CCT and thromboelastometry. METHODS: This is a
      retrospective, observational study conducted in medical-surgical intensive care
      unit (ICU). Adult patients (>=18 years) admitted to ICU between November 2012 and
      December 2014, in whom ROTEM analyses were performed for bleeding management were
      included in this study. The first ROTEM and CCT after ICU admission were recorded
      simultaneously. Additionally, we collected data on blood components transfusion
      and hemostatic agents immediately after laboratory tests results. RESULTS: The
      study included 531 patients. Most ROTEM tests showed normal coagulation profile
      [INTEM (54.8%), EXTEM (54.1%) and FIBTEM (53.3%)] with divergent results in
      relation to CCT: low platelet count (51.8% in INTEM and 55.9% in EXTEM);
      prolonged aPTT (69.9% in INTEM and 63.7% in EXTEM) and higher INR (23.8% in INTEM
      and 27.4% in EXTEM). However 16,7% of patients with normocoagulability in ROTEM
      received platelet concentrates and 10% fresh frozen plasma. CONCLUSION: The
      predominant ROTEM profile observed in this sample of critically ill patients was
      normal. In contrast, CCT suggested coagulopathy leading to a possibly unnecessary
      allogenic blood component transfusion. ROTEM test may avoid inappropriate
      allogeneic blood products transfusion in these patients.

PMID- 29462166
TI  - Oncologic emergencies in a cancer center emergency department and in general
      emergency departments countywide and nationwide.
AB  - BACKGROUND: Although cancer patients (CPs) are increasingly likely to visit
      emergency department (ED), no population-based study has compared the
      characteristics of CPs and non-cancer patients (NCPs) who visit the ED and
      examined factors associated with hospitalization via the ED. In this study, we
      (1) compared characteristics and diagnoses between CPs and NCPs who visited the
      ED in a cancer center or general hospital; (2) compared characteristics and
      diagnoses between CPs and NCPs who were hospitalized via the ED in a cancer
      center or general hospital; and (3) investigated important factors associated
      with such hospitalization. METHODS AND FINDINGS: We analyzed patient
      characteristic and diagnosis [based on International Classification of Diseases-9
      (ICD-9) codes] data from the ED of a comprehensive cancer center (MDACC), 24
      general EDs in Harris County, Texas (HCED), and the National Hospital Ambulatory
      Medical Care Survey (NHAMCS) from 1/1/2007-12/31/2009. Approximately 3.4 million
      ED visits were analyzed: 47,245, 3,248,973, and 104,566 visits for MDACC, HCED,
      and NHAMCS, respectively, of which 44,143 (93.4%), 44,583 (1.4%), and 632 (0.6%)
      were CP visits. CPs were older than NCPs and stayed longer in EDs. Lung,
      gastrointestinal (excluding colorectal), and genitourinary (excluding prostate)
      cancers were the three most common diagnoses related to ED visits at general EDs.
      CPs visiting MDACC were more likely than CPs visiting HCED to be privately
      insured. CPs were more likely than NCPs to be hospitalized. Pneumonia and
      influenza, fluid and electrolyte disorders, and fever were important predictive
      factors for CP hospitalization; coronary artery disease, cerebrovascular disease,
      and heart failure were important factors for NCP hospitalization. CONCLUSIONS:
      CPs consumed more ED resources than NCPs and had a higher hospitalization rate.
      Given the differences in characteristics and diagnoses between CPs and NCPs, ED
      physicians must pay special attention to CPs and be familiar with their unique
      set of oncologic emergencies.

PMID- 29462167
TI  - Prediction of infectious disease epidemics via weighted density ensembles.
AB  - Accurate and reliable predictions of infectious disease dynamics can be valuable
      to public health organizations that plan interventions to decrease or prevent
      disease transmission. A great variety of models have been developed for this
      task, using different model structures, covariates, and targets for prediction.
      Experience has shown that the performance of these models varies; some tend to do
      better or worse in different seasons or at different points within a season.
      Ensemble methods combine multiple models to obtain a single prediction that
      leverages the strengths of each model. We considered a range of ensemble methods
      that each form a predictive density for a target of interest as a weighted sum of
      the predictive densities from component models. In the simplest case, equal
      weight is assigned to each component model; in the most complex case, the weights
      vary with the region, prediction target, week of the season when the predictions
      are made, a measure of component model uncertainty, and recent observations of
      disease incidence. We applied these methods to predict measures of influenza
      season timing and severity in the United States, both at the national and
      regional levels, using three component models. We trained the models on
      retrospective predictions from 14 seasons (1997/1998-2010/2011) and evaluated
      each model's prospective, out-of-sample performance in the five subsequent
      influenza seasons. In this test phase, the ensemble methods showed average
      performance that was similar to the best of the component models, but offered
      more consistent performance across seasons than the component models. Ensemble
      methods offer the potential to deliver more reliable predictions to public health
      decision makers.

PMID- 29462168
TI  - Risk and surrogate benefit for pediatric Phase I trials in oncology: A systematic
      review with meta-analysis.
AB  - BACKGROUND: Pediatric Phase I cancer trials are critical for establishing the
      safety and dosing of anti-cancer treatments in children. Their implementation,
      however, must contend with the rarity of many pediatric cancers and limits on
      allowable risk in minors. The aim of this study is to describe the risk and
      benefit for pediatric cancer Phase I trials. METHODS AND FINDINGS: Our protocol
      was prospectively registered in PROSPERO (CRD42015015961). We systematically
      searched Embase and PubMed for solid and hematological malignancy Phase I
      pediatric trials published between 1 January 2004 and 1 March 2015. We included
      pediatric cancer Phase I studies, defined as "small sample size, non-randomized,
      dose escalation studies that defined the recommended dose for subsequent study of
      a new drug in each schedule tested." We measured risk using grade 3, 4, and 5
      (fatal) drug-related adverse events (AEs) and benefit using objective response
      rates. When possible, data were meta-analyzed. We identified 170 studies meeting
      our eligibility criteria, accounting for 4,604 patients. The pooled overall
      objective response rate was 10.29% (95% CI 8.33% to 12.25%), and was lower in
      solid tumors, 3.17% (95% CI 2.62% to 3.72%), compared with hematological
      malignancies, 27.90% (95% CI 20.53% to 35.27%); p < 0.001. The overall fatal
      (grade 5) AE rate was 2.09% (95% CI 1.45% to 2.72%). Across the 4,604 evaluated
      patients, there were 4,675 grade 3 and 4 drug-related AEs, with an average grade
      3/4 AE rate per person equal to 1.32. Our study had the following limitations:
      trials included in our review were heterogeneous (to minimize heterogeneity, we
      separated types of therapy and cancer types), and we relied on published data
      only and encountered challenges with the quality of reporting. CONCLUSIONS: Our
      meta-analysis suggests that, on the whole, AE and response rates in pediatric
      Phase I trials are similar to those in adult Phase I trials. Our findings provide
      an empirical basis for the refinement and review of pediatric Phase I trials, and
      for communication about their risk and benefit.

PMID- 29462169
TI  - Characteristics and predictors for gastrointestinal hemorrhage among adult
      patients with dengue virus infection: Emphasizing the impact of existing comorbid
      disease(s).
AB  - BACKGROUND: Gastrointestinal (GI) bleeding is a leading cause of death in dengue.
      This study aims to identify predictors for GI bleeding in adult dengue patients,
      emphasizing the impact of existing comorbid disease(s). METHODS: Of 1300 adults
      with dengue virus infection, 175 (mean age, 56.5+/-13.7 years) patients with GI
      bleeding and 1,125 (mean age, 49.2+/-15.6 years) without GI bleeding (controls)
      were retrospectively analyzed. RESULTS: Among 175 patients with GI bleeding,
      dengue hemorrhagic fever was found in 119 (68%) patients; the median duration
      from onset dengue illness to GI bleeding was 5 days. Gastric ulcer, erythematous
      gastritis, duodenal ulcer, erosive gastritis, and hemorrhagic gastritis were
      found in 52.3%, 33.3%, 28.6%, 28.6%, and 14.3% of 42 patients with GI bleeding
      who had undergone endoscopic examination, respectively. Overall, nine of the 175
      patients with GI bleeding died, giving an in-hospital mortality rate of 5.1%.
      Multivariate analysis showed age >=60 years (cases vs. controls: 48% vs. 28.3%)
      (odds ratio [OR]: 1.663, 95% confidence interval [CI]: 1.128-2.453), end stage
      renal disease with additional comorbidities (cases vs. controls: 1.7% vs. 0.2%)
      (OR: 9.405, 95% CI: 1.4-63.198), previous stroke with additional comorbidities
      (cases vs. controls: 7.4% vs. 0.6%) (OR: 9.772, 95% CI: 3.302-28.918), gum
      bleeding (cases vs. controls: 27.4% vs. 11.5%) (OR: 1.732, 95% CI: 1.1-2.727),
      petechiae (cases vs. controls: 56.6% vs. 29.1%) (OR: 2.109, 95% CI: 1.411-3.153),
      and platelet count <50*109 cells/L (cases vs. controls: 53.1% vs. 25.8%) (OR:
      3.419, 95% CI: 2.103-5.558) were independent predictors of GI bleeding in
      patients with dengue virus infection. CONCLUSIONS: Our study is the first to
      disclose that end stage renal disease and previous stroke, with additional
      comorbidities, were strongly significant associated with the risk of GI bleeding
      in patients with dengue virus infection. Identification of these risk factors can
      be incorporated into the patient assessment and management protocol of dengue
      virus infection to reduce its mortality.

PMID- 29462170
TI  - Mitochondrial DNA variants of Podolian cattle breeds testify for a dual maternal
      origin.
AB  - BACKGROUND: Over the past 15 years, 300 out of 6000 breeds of all farm animal
      species identified by the Food and Agriculture Organization of the United Nations
      (FAO) have gone extinct. Among cattle, many Podolian breeds are seriously
      endangered in various European areas. Podolian cattle include a group of very
      ancient European breeds, phenotypically close to the aurochs ancestors (Bos
      primigenius). The aim of the present study was to assess the genetic diversity of
      Podolian breeds and to reconstruct their origin. METHODOLOGY: The mitochondrial
      DNA (mtDNA) control-regions of 18 Podolian breeds have been phylogenetically
      assessed. Nine non-Podolian breeds have been also included for comparison.
      CONCLUSION: The overall analysis clearly highlights some peculiarities in the
      mtDNA gene pool of some Podolian breeds. In particular, a principal component
      analysis point to a genetic proximity between five breeds (Chianina, Marchigiana,
      Maremmana, Podolica Italiana and Romagnola) reared in Central Italy and the
      Turkish Grey. We here propose the suggestive hypothesis of a dual ancestral
      contribution to the present gene pool of Podolian breeds, one deriving from
      Eastern European cattle; the other arising from the arrival of Middle Eastern
      cattle into Central Italy through a different route, perhaps by sea, ferried by
      Etruscan boats. The historical migration of Podolian cattle from North Eastern
      Europe towards Italy has not cancelled the mtDNA footprints of this previous
      ancient migration.

PMID- 29462171
TI  - Stigma gets in my way: Factors affecting client-provider communication regarding
      childbearing among people living with HIV in Uganda.
AB  - INTRODUCTION: Many HIV-affected couples living in sub-Saharan Africa desire to
      have children, but few quantitative studies have examined support for their
      childbearing needs. Our study explored client-provider communication about
      childbearing and safer conception among HIV clients in Uganda. METHODS: 400
      Ugandan HIV clients in committed relationships and with intentions to conceive
      were surveyed. Knowledge, attitudes and practices related to childbearing, and
      use of safer conception methods were assessed, including communication with
      providers about childbearing needs, the correlates of which were examined with
      bivariate statistics and logistic multivariate analysis. RESULTS: 75% of the
      sample was female; 61% were on antiretroviral therapy; and 61% had HIV-negative
      or unknown status partners. Nearly all (98%) reported the desire to discuss
      childbearing intentions with their HIV provider; however, only 44% reported such
      discussions, the minority (28%) of which was initiated by the provider. Issues
      discussed with HIV providers included: HIV transmission risk to partner (30%),
      HIV transmission risk to child (30%), and how to prevent transmission to the
      child (27%); only 8% discussed safer conception methods. Regression analysis
      showed that those who had communicated with providers about childbearing were
      more likely to have been diagnosed with HIV for a longer period [OR (95% CI) =
      1.09 (1.03, 1.15)], while greater internalized childbearing stigma was associated
      with lower odds of this communication [OR (95% CI) = 0.70 (0.49, 0.99)], after
      controlling for all bivariate correlates and basic demographics. CONCLUSIONS:
      Communication between HIV clients and providers about childbearing needs is poor
      and associated with stigma. Innovations to mitigate stigma among clients as well
      as training to improve health worker communication and skills related to safer
      conception counseling is needed.

PMID- 29462172
TI  - Hemostatic findings of pleural fluid in dogs and the association between pleural
      effusions and primary hyperfibrino(geno)lysis: A cohort study of 99 dogs.
AB  - The primary objective of this study was to determine if activation of coagulation
      and fibrinolysis occurs in canine pleural effusions. Thirty-three dogs with
      pleural effusions of different origin were studied. Pleural effusion fibrinogen
      concentrations were significantly lower, while pleural fibrin-fibrinogen
      degradation products (FDPs) and D-dimer concentrations were significantly higher
      than those in plasma (P < 0.001 for all comparisons). These results show that, in
      canine pleural fluids, there is evidence of coagulation activation and
      fibrinolysis. The secondary aims of the current study were to determine if
      primary hyperfibrinolysis ([PHF] i.e., elevated plasma FDPs with a normal D-dimer
      concentrations), occurs in dogs with pleural effusion, and whether the presence
      of a concurrent inflammatory process may have activated the hemostatic cascade,
      with its intrinsically linked secondary hyperfibrinolysis, masking the concurrent
      PHF. The previously 33 selected dogs with pleural effusion (group 1) were
      compared to two control groups of 33 healthy (group 2) and 33 sick dogs without
      pleural effusion (group 3). Serum fibrinogen, FDPs, D-dimer, C-reactive protein
      (CRP), fibrinogen/CRP ratio, and frequency of PHF were determined. Fibrinogen,
      FDPs, D-dimer and CRP concentrations in group 1 were significantly increased
      compared to group 2 (P < 0.001 for all comparisons). FDPs and CRP concentrations
      in group 1 were also significantly increased compared to group 3 (P = 0.001 and P
      < 0.001, respectively). The fibrinogen/CRP ratio was significantly decreased in
      group 1 compared to groups 2 and 3 (P < 0.001 for both comparison). The frequency
      of PHF was significantly higher in group 1 compared to groups 2 (P = 0.004), but
      not compared to group 3. These results support the hypothesis that PHF occurs
      significantly more often in dogs with pleural effusion compared to healthy dogs.
      Nevertheless, the decrease in the fibrinogen/CRP ratio in group 1 compared to
      group 3, considering the higher FDPs and similar D-dimer concentrations, would
      suggest that PHF is also more frequent in dogs with pleural effusion compared to
      sick control dogs, and that this phenomenon is hidden due to concurrent secondary
      hyperfibrinolysis.

PMID- 29462173
TI  - Imaging cellular pharmacokinetics of 18F-FDG and 6-NBDG uptake by inflammatory
      and stem cells.
AB  - OBJECTIVES: Myocardial infarction (MI) causes significant loss of cardiomyocytes,
      myocardial tissue damage, and impairment of myocardial function. The inability of
      cardiomyocytes to proliferate prevents the heart from self-regeneration. The
      treatment for advanced heart failure following an MI is heart transplantation
      despite the limited availability of the organs. Thus, stem-cell-based cardiac
      therapies could ultimately prevent heart failure by repairing injured myocardium
      that reverses cardiomyocyte loss. However, stem-cell-based therapies lack
      understanding of the mechanisms behind a successful therapy, including difficulty
      tracking stem cells to provide information on cell migration, proliferation and
      differentiation. In this study, we have investigated the interaction between
      different types of stem and inflammatory cells and cell-targeted imaging
      molecules, 18F-FDG and 6-NBDG, to identify uptake patterns and pharmacokinetics
      in vitro. METHODS: Macrophages (both M1 and M2), human induced pluripotent stem
      cells (hiPSCs), and human amniotic mesenchymal stem cells (hAMSCs) were incubated
      with either 18F-FDG or 6-NBDG. Excess radiotracer and fluorescence were removed
      and a 100 MUm-thin CdWO4 scintillator plate was placed on top of the cells for
      radioluminescence microscopy imaging of 18F-FDG uptake, while no scintillator was
      needed for fluorescence imaging of 6-NBDG uptake. Light produced following beta
      decay was imaged with a highly sensitive inverted microscope (LV200, Olympus) and
      an Electron Multiplying Charge-Couple Device (EM-CCD) camera. Custom-written
      software was developed in MATLAB for image processing. RESULTS: The average
      cellular activity of 18F-FDG in a single cell of hAMSCs (0.670+/-0.028 fCi/MUm2,
      P = 0.001) was 20% and 36% higher compared to uptake in hiPSCs (0.540+/-0.026
      fCi/MUm2, P = 0.003) and macrophages (0.430+/-0.023 fCi/MUm2, P = 0.002),
      respectively. hAMSCs exhibited the slowest influx (0.210 min-1) but the fastest
      efflux (0.327 min-1) rate compared to the other tested cell lines for 18F-FDG.
      This cell line also has the highest phosphorylation but exhibited the lowest rate
      of de-phosphorylation. The uptake pattern for 6-NBDG was very different in these
      three cell lines. The average cellular activity of 6-NBDG in a single cell of
      macrophages (0.570+/-0.230 fM/MUm2, P = 0.004) was 38% and 14% higher compared to
      hiPSCs (0.350+/-0.160 fM/MUm2, P = 0.001) and hAMSCs (0.490+/-0.028 fM/MUm2, P =
      0.006), respectively. The influx (0.276 min-1), efflux (0.612 min-1),
      phosphorylation (0.269 min-1), and de-phosphorylation (0.049 min-1) rates were
      also highest for macrophages compared to the other two tested cell lines.
      CONCLUSION: hAMSCs were found to be 2-3* more sensitive to 18F-FDG molecule
      compared to hiPSCs/macrophages. However, macrophages exhibited the most
      sensitivity towards 6-NBDG. Based on this result, hAMSCs targeted with 18F-FDG
      could be more suitable for understanding the mechanisms behind successful therapy
      for treating MI patients by gathering information on cell migration,
      proliferation and differentiation.

PMID- 29462174
TI  - Exposure to 1.8 GHz electromagnetic fields affects morphology, DNA-related Raman
      spectra and mitochondrial functions in human lympho-monocytes.
AB  - Blood is a fluid connective tissue of human body, where it plays vital functions
      for the nutrition, defense and well-being of the organism. When circulating in
      peripheral districts, it is exposed to some physical stresses coming from outside
      the human body, as electromagnetic fields (EMFs) which can cross the skin. Such
      fields may interact with biomolecules possibly inducing non thermal-mediated
      biological effects at the cellular level. In this study, the occurrence of
      biochemical/biological modifications in human peripheral blood lympho-monocytes
      exposed in a reverberation chamber for times ranging from 1 to 20 h to EMFs at
      1.8 GHz frequency and 200 V/m electric field strength was investigated.
      Morphological analysis of adherent cells unveiled, in some of these, appearance
      of an enlarged and deformed shape after EMFs exposure. Raman spectra of the
      nuclear compartment of cells exposed to EMFs revealed the onset of biochemical
      modifications, mainly consisting in the reduction of the DNA backbone-linked
      vibrational modes. Respirometric measurements of mitochondrial activity in intact
      lympho-monocytes resulted in increase of the resting oxygen consumption rate
      after 20 h of exposure, which was coupled to a significant increase of the FoF1
      ATP synthase-related oxygen consumption. Notably, at lower time-intervals of EMFs
      exposure (i.e. 5 and 12 h) a large increase of the proton leak-related
      respiration was observed which, however, recovered at control levels after 20 h
      exposure. Confocal microscopy analysis of the mitochondrial membrane potential
      supported the respiratory activities whereas no significant variations in the
      mitochondrial mass/morphology was observed in EMFs-exposed lympho-monocytes.
      Finally, altered redox homeostasis was shown in EMFs-exposed lympho-monocytes,
      which progressed differently in nucleated cellular subsets. This results suggest
      the occurrence of adaptive mechanisms put in action, likely via redox signaling,
      to compensate for early impairments of the oxidative phosphorylation system
      caused by exposure to EMFs. Overall the data presented warn for health safety of
      people involved in long-term exposure to electromagnetic fields, although further
      studies are required to pinpoint the leukocyte cellular subset(s) selectively
      targeted by the EMFs action and the mechanisms by which it is achieved.

PMID- 29462175
TI  - Effect of cataract surgery on cognitive function in elderly: Results of Fujiwara
      kyo Eye Study.
AB  - PURPOSE: To determine whether there is a significant association between prior
      cataract surgery and cognitive function in an elderly Japanese cohort. SETTING:
      Nara Medical University, Nara, Japan. DESIGN: The Fujiwara-kyo Eye Study was a
      cross-sectional epidemiological study. METHODS: The subjects were >= 68-years who
      lived in the Nara Prefecture and responded to recruitment notices. All of the
      subjects received comprehensive ophthalmological examinations, and answered
      questionnaires on their socio-demographic and medical history including prior
      cataract surgery. The association between prior cataract surgery and cognitive
      function was determined. RESULTS: A total of the 2764 subjects whose mean age was
      76.3+/-4.8 years (+/-standard deviation) was studied. Of these, 668 individuals
      (24.2%) had undergone cataract surgery. Of these, 150 (5.4%) had dementia as
      determined by the Mini-Mental State Examination (MMSE) score <=23, and 877
      individuals (31.7%) had mild cognitive impairment (MCI; MMSE score 24-26). The
      subjects who had prior cataract surgery had significantly lower odds ratio (OR)
      of having MCI (OR = 0.78, 95% confidence interval; CI 0.64-0.96, P = 0.019) than
      those who had not had cataract surgery after adjusting for age, sex, body mass
      index, education, hypertension, diabetes, depression, and history of stroke. The
      OR was still lower when the visual acuity was also added to the adjusted factors
      (OR 0.79, 95% CI 0.64-0.97, P = 0.025). However, prior cataract surgery did not
      contribute significantly to the low OR for dementia. CONCLUSIONS: Cataract
      surgery may play a role in reducing the risk of developing MCI independently of
      visual acuity but not for dementia.

PMID- 29462176
TI  - Outcome of Enterococcus faecalis infective endocarditis according to the length
      of antibiotic therapy: Preliminary data from a cohort of 78 patients.
AB  - BACKGROUND: International guidelines recommend 4 weeks of treatment with
      ampicillin plus gentamicin (A+G) for uncomplicated native valve Enterococcus
      faecalis infective endocarditis (EFIE) and 6 weeks in the remaining cases.
      Ampicillin plus ceftriaxone (A+C) is always recommended for at least 6w, with no
      available studies assessing its suitability for 4w. We aimed to investigate
      differences in the outcome of EFIE according to the duration (4 versus 6 weeks)
      of antibiotic treatment (A+G or A+C). METHODS: Retrospective analysis from a
      prospectively collected cohort of 78 EFIE patients treated with either A+G or
      A+C. RESULTS: 32 cases (41%) were treated with A+G (9 for 4w, 28%) and 46 (59%)
      with A+C (14 for 4w, 30%). No significant differences were found in 1-year
      mortality according to the type of treatment (31% and 24% in A+G and A+C,
      respectively; P = 0.646) or duration (26% and 27% at 4 and 6w, respectively; P =
      0.863). Relapses were more frequent among survivors treated for 4w than in those
      treated for 6w (3/18 [17%] at 4w and 1/41 [2%] at 6w; P = 0.045). Three out of 4
      (75%) relapses occurred in cirrhotic patients. CONCLUSIONS: A 4-week course of
      antibiotic treatment might not be suitable neither for A+G nor A+C for treating
      uncomplicated native valve EFIE.

PMID- 29462177
TI  - Improving stability of prediction models based on correlated omics data by using
      network approaches.
AB  - Building prediction models based on complex omics datasets such as
      transcriptomics, proteomics, metabolomics remains a challenge in bioinformatics
      and biostatistics. Regularized regression techniques are typically used to deal
      with the high dimensionality of these datasets. However, due to the presence of
      correlation in the datasets, it is difficult to select the best model and
      application of these methods yields unstable results. We propose a novel strategy
      for model selection where the obtained models also perform well in terms of
      overall predictability. Several three step approaches are considered, where the
      steps are 1) network construction, 2) clustering to empirically derive modules or
      pathways, and 3) building a prediction model incorporating the information on the
      modules. For the first step, we use weighted correlation networks and Gaussian
      graphical modelling. Identification of groups of features is performed by
      hierarchical clustering. The grouping information is included in the prediction
      model by using group-based variable selection or group-specific penalization. We
      compare the performance of our new approaches with standard regularized
      regression via simulations. Based on these results we provide recommendations for
      selecting a strategy for building a prediction model given the specific goal of
      the analysis and the sizes of the datasets. Finally we illustrate the advantages
      of our approach by application of the methodology to two problems, namely
      prediction of body mass index in the DIetary, Lifestyle, and Genetic determinants
      of Obesity and Metabolic syndrome study (DILGOM) and prediction of response of
      each breast cancer cell line to treatment with specific drugs using a breast
      cancer cell lines pharmacogenomics dataset.

PMID- 29462178
TI  - Understanding N timing in corn yield and fertilizer N recovery: An insight from
      an isotopic labeled-N determination.
AB  - Early fertilizer nitrogen (N) application on cover crops or their residues during
      the off-season is a practice adopted in Brazil subtropical conditions under no
      tillage corn (Zea mays L.) systems. However, the effect of early N application on
      yield, plant N content, and N recovery efficiency (NRE) for corn is not yet well
      documented. Five fertilizer N timings in an oat-corn system were evaluated in two
      studies utilizing an isotopic-labeled N determination, 15N isotope. The N
      fertilization timings were: (i) oat tillering, (ii) 15 days before corn planting
      time, over the oat residues, (iii) at corn planting time, (iv) in-season at the
      three-leaf growth stage (V3), and (v) in-season split application at V3 and six
      leaf (V6) growth stages. Based on the statistical analysis, the N fertilization
      timings were separated into three groups: 1) N-OATS, designated to N applied at
      oat; 2) N-PLANT, referred to pre-plant and planting N applications; and 3) N
      CORN, designated to in-season corn N applications. Corn yield was not affected by
      the N fertilization timing. However, the N-CORN N fertilization timings enhanced
      NRE by 17% and 35% and final N recovery system (plant plus soil) by 16% and 24%
      all relative to N-OATS and N-PLANT groups, respectively. Overall, N-OATS resulted
      in the largest N derived from fertilizer (NDFF) amount in the deeper soil layer,
      in overall a delta of 10 kg N ha-1 relative to the rest of the groups.
      Notwithstanding corn yield was not affected, early N fertilization under
      subtropical conditions is not a viable option since NRE was diminished and the
      non-recovery N increased relative to the in-season N applications.

PMID- 29462180
TI  - Physician referral patterns and racial disparities in total hip replacement: A
      network analysis approach.
AB  - BACKGROUND: Efforts to reduce racial disparities in total hip replacement (THR)
      have focused mainly on patient behaviors. While these efforts are no doubt
      important, they ignore the potentially important role of provider- and system
      level factors, which may be easier to modify. We aimed to determine whether the
      patterns of interaction among physicians around THR episodes differ in
      communities with low versus high concentrations of black residents. MATERIALS AND
      METHODS: We analyzed national Medicare claims from 2008 to 2011, identifying all
      fee-for-service beneficiaries who underwent THR. Based on physician encounter
      data, we then mapped the physician referral networks at the hospitals where
      beneficiaries' procedures were performed. Next, we measured two structural
      properties of these networks that could affect care coordination and information
      sharing: clustering, and the number of external ties. Finally, we estimated
      multivariate regression models to determine the relationship between the
      concentration of black residents in the community [as measured by the hospital
      service area (HSA)] served by a given network and each of these 2 network
      properties. RESULTS: Our sample included 336,506 beneficiaries (mean age 76.3 +/-
      SD), 63.1% of whom were women. HSAs with higher concentrations of black residents
      tended to be more impoverished than those with lower concentrations. While HSAs
      with higher concentrations of black residents had, on average, more acute care
      beds and medical specialists, they had fewer surgeons per capita than those with
      lower concentrations. After adjusting for these differences, we found that HSAs
      with higher concentrations of black residents were served by physician referral
      networks that had significantly higher within-network clustering but fewer
      external ties. CONCLUSIONS: We observed differences in the patterns of
      interaction among physicians around THR episodes in communities with low versus
      high concentrations of black residents. Studies investigating the impact of these
      differences on access to quality providers and on THR outcomes are needed.

PMID- 29462179
TI  - Patient navigators for people with chronic disease: A systematic review.
AB  - BACKGROUND: People with chronic diseases experience barriers to managing their
      diseases and accessing available health services. Patient navigator programs are
      increasingly being used to help people with chronic diseases navigate and access
      health services. OBJECTIVE: The objective of this review was to summarize the
      evidence for patient navigator programs in people with a broad range of chronic
      diseases, compared to usual care. METHODS: We searched MEDLINE, EMBASE, CENTRAL,
      CINAHL, PsycINFO, and Social Work Abstracts from inception to August 23, 2017. We
      also searched the reference lists of included articles. We included original
      reports of randomized controlled trials of patient navigator programs compared to
      usual care for adult and pediatric patients with any one of a defined set of
      chronic diseases. RESULTS: From a total of 14,672 abstracts, 67 unique studies
      fit our inclusion criteria. Of these, 44 were in cancer, 8 in diabetes, 7 in
      HIV/AIDS, 4 in cardiovascular disease, 2 in chronic kidney disease, 1 in dementia
      and 1 in patients with more than one condition. Program characteristics varied
      considerably. Primary outcomes were most commonly process measures, and 45 of 67
      studies reported a statistically significant improvement in the primary outcome.
      CONCLUSION: Our findings indicate that patient navigator programs improve
      processes of care, although few studies assessed patient experience, clinical
      outcomes or costs. The inability to definitively outline successful components
      remains a key uncertainty in the use of patient navigator programs across chronic
      diseases. Given the increasing popularity of patient navigators, future studies
      should use a consistent definition for patient navigation and determine which
      elements of this intervention are most likely to lead to improved outcomes. TRIAL
      REGISTRATION: PROSPERO #CRD42013005857.

PMID- 29462181
TI  - Association between somatic symptom burden and health-related quality of life in
      people with chronic low back pain.
AB  - Depression is a relevant risk factor for low back pain and is associated with the
      outcomes of low back pain. Depression also often overlaps with somatisation. As
      previous studies have suggested that somatisation or a higher somatic symptom
      burden has a role in the outcomes of low back pain, the aim of the present cross
      sectional study was to examine whether somatic symptom burden was associated with
      health-related quality of life in individuals with chronic low back pain
      independent of depression. We analyzed internet survey data on physical and
      mental health in Japanese adults aged 20-64 years with chronic low back pain (n =
      3,100). Health-related quality of life was assessed using the EuroQol five
      dimensions (EQ-5D) questionnaire. Somatic symptom burden and depression were
      assessed using the Somatic Symptom Scale-8 (SSS-8) and the Patient Health
      Questionnaire-2 (PHQ-2), respectively. SSS-8 score was categorized as no to
      minimal (0-3), low (4-7), medium (8-11), high (12-15), and very high (16-32). The
      association between SSS-8 and EQ-5D was examined using linear regression models,
      adjusting for depression and other covariates, including age, sex, BMI, smoking,
      marital status, education, exercise, employment, and the number of comorbid
      diseases. A higher somatic symptom burden was significantly associated with a
      lower health-related quality of life independent of depression and the number of
      comorbid diseases (regression coefficient = 0.040 for SSS-8 high vs. very high
      and 0.218 for non to minimal vs. very high, p trend <0.0001). In conclusion,
      somatic symptom burden might be important for the health-related quality of life
      of individuals with chronic low back pain.

PMID- 29462182
TI  - Exercise-induced cardiac remodeling in non-elite endurance athletes: Comparison
      of 2-tiered and 4-tiered classification of left ventricular hypertrophy.
AB  - BACKGROUND: Long-term endurance sport practice leads to eccentric left
      ventricular hypertrophy (LVH). We aimed to compare the new 4-tiered
      classification (4TC) for LVH with the established 2-tiered classification (2TC)
      in a cohort of normotensive non-elite endurance athletes. METHODS: Male
      participants of a 10-mile race were recruited and included when blood pressure
      (BP) was normal (<140/90 mmHg). Phenotypic characterization of LVH was based on
      relative wall thickness (2TC), and on LV concentricity2/3 (LV mass/end-diastolic
      volume [LVM/EDV]2/3) plus LVEDV index (4TC). Parameters of LV geometry, BP,
      cumulative training hours, and race time were compared between 2TC and 4TC by
      analysis of variance, and post-hoc analysis. RESULTS: Of 198 athletes recruited,
      174 were included. Mean age was 41.6+/-7.5 years. Forty-two (24%) athletes had
      LVH. Allocation in the 2TC was: 32 (76%) eccentric LVH and 10 (24%) concentric
      LVH. Using the 4TC 12 were reclassified to concentric LVH, and 2 to eccentric
      LVH, resulting in 22 (52%) eccentric LVH (7 non-dilated, 15 dilated), and 20
      (48%) concentric LVH (all non-dilated). Based on the 2TC, markers of endurance
      training did not differ between eccentric and concentric LVH. Based on the 4TC,
      athletes with eccentric LVH had more cumulative training hours and faster race
      times, with highest values thereof in athletes with eccentric dilated LVH.
      CONCLUSIONS: In our cohort of normotensive endurance athletes, the new 4TC
      demonstrated a superior discrimination of exercise-induced LVH patterns, compared
      to the established 2TC, most likely because it takes three-dimensional
      information of the ventricular geometry into account.

PMID- 29462183
TI  - Galanin is an epigenetically silenced tumor suppressor gene in gastric cancer
      cells.
AB  - Galanin is a 30 amino-acid active neuropeptide that acts via three G-protein
      coupled galanin receptors, GALR1, GALR2 and GALR3. Recently, GALR1 was also
      suggested as a tumor suppressor gene that was frequently silenced in head and
      neck squamous cell carcinoma; moreover, galanin and GALR1 were reported to
      inhibit human oral cancer cell proliferation. However, the exact role of galanin
      in gastric cancer is unclear. Here, we describe the epigenetic silencing of
      galanin in human gastric cancer. Five gastric cancer cell lines (SNU-1, SNU-601,
      SNU-638, KATOIII, and AGS) showed a significant reduction in galanin expression
      that was restored by the demethylating agent 5-aza-2'-deoxycytidine. We confirmed
      the hypermethylation of CpG islands in the galanin promoter region by methylation
      specific and bisulfate sequencing polymerase chain reaction (PCR). Interestingly,
      hypermethylated galanin did not affect galanin receptor expression. Exogenous
      galanin expression in silenced cells induced apoptosis and decreased
      phosphorylated Akt expression. Taken together, these data suggest that galanin
      hypermethylation impairs its tumor suppressor function in gastric cancer
      carcinogenesis.

PMID- 29462184
TI  - Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in
      infected cells reveals ATPase Na+/K+ transporting subunit Alpha 1 and prohibitin
      as host-cell factors involved in the life cycle of mammarenaviruses.
AB  - Several mammalian arenaviruses (mammarenaviruses) cause hemorrhagic fevers in
      humans and pose serious public health concerns in their endemic regions.
      Additionally, mounting evidence indicates that the worldwide-distributed,
      prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a
      neglected human pathogen of clinical significance. Concerns about human
      pathogenic mammarenaviruses are exacerbated by of the lack of licensed vaccines,
      and current anti-mammarenavirus therapy is limited to off-label use of ribavirin
      that is only partially effective. Detailed understanding of virus/host-cell
      interactions may facilitate the development of novel anti-mammarenavirus
      strategies by targeting components of the host-cell machinery that are required
      for efficient virus multiplication. Here we document the generation of a
      recombinant LCMV encoding a nucleoprotein (NP) containing an affinity tag
      (rLCMV/Strep-NP) and its use to capture the NP-interactome in infected cells. Our
      proteomic approach combined with genetics and pharmacological validation assays
      identified ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) and prohibitin
      (PHB) as pro-viral factors. Cell-based assays revealed that ATP1A1 and PHB are
      involved in different steps of the virus life cycle. Accordingly, we observed a
      synergistic inhibitory effect on LCMV multiplication with a combination of ATP1A1
      and PHB inhibitors. We show that ATP1A1 inhibitors suppress multiplication of
      Lassa virus and Candid#1, a live-attenuated vaccine strain of Junin virus,
      suggesting that the requirement of ATP1A1 in virus multiplication is conserved
      among genetically distantly related mammarenaviruses. Our findings suggest that
      clinically approved inhibitors of ATP1A1, like digoxin, could be repurposed to
      treat infections by mammarenaviruses pathogenic for humans.

PMID- 29462186
TI  - Lack of infrastructure, social and cultural factors limit physical activity among
      patients with type 2 diabetes in rural Sri Lanka, a qualitative study.
AB  - INTRODUCTION: South Asians have high prevalence of diabetes, increased
      cardiovascular risk and low levels of physical activity (PA). Reasons for low
      levels of PA have not previously been explored among Asians living within their
      endogenous environment. This qualitative study was performed to explore the
      contextual reasons that limited PA among type 2 diabetic patients living in a
      rural community. METHODS: Purposeful sampling recruited 40 participants with long
      standing type 2 diabetes for this qualitative study. Semi-structered questions
      utilising in-depth interviews were used to collect data on PA patterns, barriers
      to PA and factors that would facilitate PA. The interviews were digitally
      recorded and transcribed. Data were analyzed using a framework approach. RESULTS:
      The sample consisted of 11 males and 29 females. Mean age was 55.4 (SD 8.9)
      years. The mean duration of diabetes in the study population was 8.5 (SD 6.8)
      years. Inability to differentitate household and daily activities from PA emerged
      as a recurring theme. Most did not have a clear understanding of the type or
      duration of PA that they should perform. Health related issues, lifestyle and
      time management, envronmental and social factors like social embarrassment,
      prioritizing household activities over PA were important factors that limited PA.
      Most stated that the concept of exercising was alien to their culture and
      lifestyle. CONCLUSION: Culturally appropriate programmes that strengthen health
      education and empower communities to overcome socio-economic barriers that limit
      PA should be implemented to better manage diabetes among rural Sri Lankan
      diabetic patients.

PMID- 29462185
TI  - DHX29 functions as an RNA co-sensor for MDA5-mediated EMCV-specific antiviral
      immunity.
AB  - Melanoma differentiation-associated gene-5 (MDA5) recognizes distinct subsets of
      viruses including Encephalomyocarditis virus (EMCV) of picornavirus family, but
      the molecular mechanisms underlying the specificity of the viral recognition of
      MDA5 in immune cells remain obscure. DHX29 is an RNA helicase required for the
      translation of 5' structured mRNA of host and many picornaviruses (such as EMCV).
      We identify that DXH29 as a key RNA co-sensor, plays a significant role for
      specific recognition and triggering anti-EMCV immunity. We have observed that
      DHX29 regulates MDA5-, but not RIG-I-, mediated type I interferon signaling by
      preferentially interacting with structured RNAs and specifically with MDA5 for
      enhancing MDA5-dsRNA binding affinity. Overall, our results identify a critical
      role for DHX29 in innate immune response and provide molecular insights into the
      mechanisms by which DHX29 recognizes 5' structured EMCV RNA and interacts with
      MDA5 for potent type I interferon signaling and antiviral immunity.

PMID- 29462187
TI  - Genotyping and sero-virological characterization of hepatitis B virus (HBV) in
      blood donors, Southern Ethiopia.
AB  - Hepatitis B virus (HBV) prevalence is highest in Sub-Saharan Africa including
      Ethiopia. HBV genotypes have distinct geographic distributions and play a role in
      course of infection and treatment management. However, in Ethiopia there is
      paucity of information about distribution of HBV genotypes. This study was done
      to determine genotype, mutation and sero-virological profiles of HBV isolates in
      Southern Ethiopia. Cross-sectional, laboratory based study was conducted on
      103HBsAg sero-positive samples from a total of 2,237 screened blood donors. HBV
      serological markers and biochemical assays were done. Serum viral load was
      measured using quantitative real-time PCR. Partial HBV S-gene was amplified with
      nested PCR and sequenced. Bioinformatics tools were utilized to determine
      genotypes, serotypes and mutations. Of 103 HBsAg reactive serum samples, 14.6%
      and 70.9% were sero-positive for HBeAg and HBeAb, respectively. Ninety-eight
      samples gave detectable viral load with a median of 3.46(2.62-4.82) log IU/ml.
      HBeAg sero-positive donors carried elevated levels of viral load. Eighty five
      isolates were successfully amplified, sequenced and genotyped into 58 (68.2%)
      genotype A (HBV/A) and 27 (31.8%) genotype D (HBV/D). HBV serotypes found were
      adw2 (74.1%), ayw2 (24.7%), and ayw3 (1.2%). In twenty-four (28.2%) samples
      mutations in the major hydrophilic region (MHR) were observed. Donors infected
      with HBV/A had higher viral load and more frequent MHR mutation than HBV/D
      infected donors. This study illustrated distribution of HBV genotype A and D
      among blood donors in southern Ethiopia. It also demonstrated occurrence HBV
      variants that may influence clinical aspects of HBV infection. The study
      contributes in narrowing the existing gap of HBV molecular study in Ethiopia.

PMID- 29462188
TI  - Correction: Definition of Human Epitopes Recognized in Tetanus Toxoid and
      Development of an Assay Strategy to Detect Ex Vivo Tetanus CD4+ T Cell Responses.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0169086.].

PMID- 29462189
TI  - Rhesus macaques form preferences for brand logos through sex and social status
      based advertising.
AB  - Like humans, monkeys value information about sex and status, inviting the
      hypothesis that our susceptibility to these factors in advertising arises from
      shared, ancestral biological mechanisms that prioritize social information. To
      test this idea, we asked whether rhesus macaques (Macaca mulatta) show choice
      behavior that is similar to humans in response to sex and social status in
      advertising. Our results show that monkeys form preferences for brand logos
      repeatedly paired with images of macaque genitals and high status monkeys.
      Moreover, monkeys sustain preferences for these brand logos even though choosing
      them provided no tangible rewards, a finding that cannot be explained by a
      decision mechanism operating solely on material outcomes. Together, our results
      endorse the hypothesis that the power of sex and status in advertising emerges
      from the spontaneous engagement of shared, ancestral neural circuits that
      prioritize information useful for navigating the social environment. Finally, our
      results show that simple associative conditioning is sufficient to explain the
      formation of preferences for brand logos paired with sexual or status-based
      images.

PMID- 29462190
TI  - Divergent bornaviruses from Australian carpet pythons with neurological disease
      date the origin of extant Bornaviridae prior to the end-Cretaceous extinction.
AB  - Tissue samples from Australian carpet pythons (Morelia spilota) with neurological
      disease were screened for viruses using next-generation sequencing. Coding
      complete genomes of two bornaviruses were identified with the gene order 3'-N-X-P
      G-M-L, representing a transposition of the G and M genes compared to other
      bornaviruses and most mononegaviruses. Use of these viruses to search available
      vertebrate genomes enabled recognition of further endogenous bornavirus-like
      elements (EBLs) in diverse placental mammals, including humans. Codivergence
      patterns and shared integration sites revealed an ancestral laurasiatherian EBLG
      integration (77 million years ago [MYA]) and a previously identified afrotherian
      EBLG integration (83 MYA). The novel python bornaviruses clustered more closely
      with these EBLs than with other exogenous bornaviruses, suggesting that these
      viruses diverged from previously known bornaviruses prior to the end-Cretaceous
      (K-Pg) extinction, 66 MYA. It is possible that EBLs protected mammals from
      ancient bornaviral disease, providing a selective advantage in the recovery from
      the K-Pg extinction. A degenerate PCR primer set was developed to detect a highly
      conserved region of the bornaviral polymerase gene. It was used to detect 15 more
      genetically distinct bornaviruses from Australian pythons that represent a group
      that is likely to contain a number of novel species.

PMID- 29462192
TI  - Correction: A refined model of claudin-15 tight junction paracellular
      architecture by molecular dynamics simulations.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184190.].

PMID- 29462191
TI  - Higher serum choline and betaine levels are associated with better body
      composition in male but not female population.
AB  - BACKGROUND: Animal studies proved that choline and betaine have beneficial effect
      on reducing body fat. However, evidence in humans is scarce. We aim to
      investigate the association between serum choline and betaine levels with body
      composition in general population. METHODS: This is an observational cross
      sectional study performed in 1081 subjects from the CODING (Complex Disease in
      Newfoundland population: Environment and Genetics) study. Serum choline and
      betaine levels were measured based on liquid chromatography coupled with tandem
      mass spectrometry technology. Body composition was measured using dual-energy X
      ray absorptiometry following a 12-hour fast. Major confounding factors including
      age, sex, total calorie intake and physical activity level were controlled in all
      analyses. RESULTS: Significantly inverse correlations were found between serum
      betaine levels and all obesity measurements in males (r ranged from -0.12 to 
      0.23, and p<0.01 for all) but not in females. Serum choline was negatively
      associated with total percent body fat (%BF), percent trunk fat (%TF), weight,
      body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (r ranged
      from -0.11 to -0.19, and p<0.05 for all) in males and positively associated with
      weight, BMI and WC (r ranged from 0.09 to 0.10, and p<0.05 for all) in females.
      The negative associations between serum choline and betaine levels with obesity
      in males were more profound in those not on any medication than those taking
      medications. Moreover, obese males had the lowest serum choline and betaine
      levels, followed by overweight males, and normal weight males having the highest
      serum choline and betaine levels, especially in those not taking medications
      (p<0.05). Likewise, subjects with the highest serum levels of both had the lowest
      obesity indexes, especially those not taking medications. CONCLUSIONS: Higher
      serum choline and betaine levels were associated with a more favorable body
      composition (lower body fat and higher lean body mass) in males and the favorable
      association was more pronounced in non-medication users.

PMID- 29462193
TI  - The influence of different fever definitions on diagnostics and treatment after
      diagnosis of fever in chemotherapy-induced neutropenia in children with cancer.
AB  - BACKGROUND: There is no evidence-based definition of the temperature limit
      defining fever (TLDF) in children with neutropenia. Lowering the TLDF is known to
      increase the number of episodes of fever in neutropenia (FN). This study aimed to
      investigate the influence of a lower versus standard TLDF on diagnostics and
      therapy. METHODS: In a single pediatric cancer center using a high standard TLDF
      (39 degrees C tympanic-temperature) patients were observed prospectively
      (NCT01683370). The effect of applying lower TLDFs (range 37.5 degrees C to 38.9
      degrees C) versus 39.0 degrees C on these measures was simulated in silicon.
      RESULTS: In reality, 45 FN episodes were diagnosed. Of 3391 temperatures
      measured, 193 were >=39.0 degrees C, and 937 >=38.0 degrees C. For persisting
      fever >=24 hours, additional blood cultures were taken in 31 (69%) episodes in
      reality. This number decreased to 22 (49%) when applying 39.0 degrees C, and
      increased to 33 for 38.0 degrees C (73%; plus 11 episodes; plus 24%). For
      persisting fever >=48 hours, i.v.-antibiotics were escalated in 25 (56%)
      episodes. This number decreased to 15 (33%) when applying 39.0 degrees C, and
      increased to 26 for 38.0 degrees C (58%; plus 11 episodes; plus 24%). For
      persisting fever >=120 hours, i.v.-antifungals were added in 4 (9%) episodes.
      This number increased to 6 (13%) by virtually applying 39.0 degrees C, and to 11
      for 38.0 degrees C (24%; plus 5 episodes; plus 11%). The median length of stay
      was 5.7 days (range, 0.8 to 43.4). In 43 episodes with hospital discharge beyond
      24 hours, applying 38.0 degrees C led to discharge delay by >=12 hours in 24
      episodes (56%; 95% CI, 40 to 71), with a median delay of 13 hours, and a
      cumulative delay of 68 days. CONCLUSION: Applying a low versus standard TLDF led
      to relevant increases of diagnostics, antimicrobial therapy, and length of stay.
      The differences between management in reality versus simply applying 39.0 degrees
      as TLDF reflect the important impact of clinical assessment.

PMID- 29462194
TI  - Enhancing healthcare accessibility measurements using GIS: A case study in Seoul,
      Korea.
AB  - With recent aging demographic trends, the needs for enhancing geo-spatial
      analysis capabilities and monitoring the status of accessibilities of its
      citizens with healthcare services have increased. The accessibility to healthcare
      is determined not only by geographic distances to service locations, but also
      includes travel time, available modes of transportation, and departure time.
      Having access to the latest and accurate information regarding the healthcare
      accessibility allows the municipal government to plan for improvements, including
      expansion of healthcare infrastructure, effective labor distribution, alternative
      healthcare options for the regions with low accessibilities, and redesigning the
      public transportation routes and schedules. This paper proposes a new method
      named, Seoul Enhanced 2-Step Floating Catchment Area (SE2SFCA), which is
      customized for the city of Seoul, where population density is higher and the
      average distance between healthcare-service locations tends to be shorter than
      the typical North American or European cities. The proposed method of SE2SFCA is
      found to be realistic and effective in determining the weak accessibility
      regions. It resolves the over-estimation issues of the past, arising from the
      assignment of high healthcare accessibility for the regions with large hospitals
      and high density of population and hospitals.

PMID- 29462195
TI  - Assessment of inhalation flow patterns of soft mist inhaler co-prescribed with
      dry powder inhaler using inspiratory flow meter for multi inhalation devices.
AB  - The patients' inhalation flow pattern is one of the significant determinants for
      clinical performance of inhalation therapy. However, the development of
      inhalation flow meters for various inhalation devices has been unable to keep up
      with the increasing number of newly launched inhalation devices. In the present
      study, we developed simple attachment orifices for the inhalation flow pattern
      monitoring system, which are suitable for all commercial inhalers, and
      investigated the efficacy of the system on the clinical inhalation instruction
      for patients co-prescribed dry powder inhaler (DPI) and soft mist inhaler (SMI).
      First, we constructed simple attachment orifices that were adjusted for 13
      commercial inhalers, and examined the correlation between orifice and inhalation
      device. Second, the inhalation flow patterns (peak inspiratory flow rate, PIFR;
      inhalation duration time, DT) of patients prescribed a combination of DPI and SMI
      were monitored before and after inhalation instruction. The inhalation resistance
      of commercial inhalers are listed in the following order; Twincaps(r) >
      Handihaler(r) > Swinghaler(r) = Clickhaler(r) > Twisthaler(r) > Turbuhaler(r) >
      Jenuair(r) > Diskus(r) = Ellipta(r) > Diskhaler(r) > Breezhaler(r) > Respimat(r)
      = pMDI. The pressure drop via orifice was significantly correlated with that via
      the commercial inhaler. For the confirmation, all participants achieved the DPI
      criterion of PIFR. On the other hand, 4 participants (6 clinical visits) of 10
      experimented participants could not achieve the essential criterion of DT (> 1.5
      sec) for SMI, but all participants improved their duration time after inhalation
      instruction by pharmacists (P<0.05). In the present study, we successfully
      developed simple attachment orifice suitable for 13 commercial inhalation
      devices. These data suggested that our simple attachment orifices for the
      inhalation flow pattern monitoring system can detect patients with inadequate
      inhalation patterns via SMI.

PMID- 29462196
TI  - Interior renovation of a general practitioner office leads to a perceptual bias
      on patient experience for over one year.
AB  - INTRODUCTION: Measuring patient experience is key when assessing quality of care
      but can be biased: A perceptual bias occurs when renovations of the interior
      design of a general practitioner (GP) office improves how patients assessed
      quality of care. The aim was to assess the length of perceptual bias and if it
      could be reproduced after a second renovation. METHODS: A GP office with 2 GPs in
      Switzerland was renovated twice within 3 years. We assessed patient experience at
      baseline, 2 months and 14 months after the first and 3 months after the second
      renovation. Each time, we invited a sample of 180 consecutive patients that
      anonymously graded patient experience in 4 domains: appearance of the office;
      qualities of medical assistants and GPs; and general satisfaction. We compared
      crude mean scores per domain from baseline until follow-up. In a multivariate
      model, we adjusted for patient's age, gender and for how long patients had been
      their GP. RESULTS: At baseline, patients aged 60.9 (17.7) years, 52% females.
      After the first renovation, we found a regression to the baseline level of
      patient experience after 14 months except for appearance of the office (p<0.001).
      After the second renovation, patient experience improved again in appearance of
      the office (p = 0.008), qualities of the GP (p = 0.008), and general satisfaction
      (p = 0.014). Qualities of the medical assistant showed a slight improvement (p =
      0.068). Results were unchanged in the multivariate model. CONCLUSIONS: Interior
      renovation of a GP office probably causes a perceptual bias for >1 year that
      improves how patients rate quality of care. This bias could be reproduced after a
      second renovation strengthening a possible causal relationship. These findings
      imply to appropriately time measurement of patient experience to at least one
      year after interior renovation of GP practices to avoid environmental changes
      influences the estimates when measuring patient experience.

PMID- 29462197
TI  - Thymic epithelial cell-derived signals control B progenitor formation and
      proliferation in the thymus by regulating Let-7 and Arid3a.
AB  - The postnatal thymus is an efficient microenvironment for T cell specification
      and differentiation. B cells are also present in the thymus and have been
      recently shown to impact T cell selection, however, the mechanisms controlling B
      cell development in the thymus are largely unknown. In Foxn1lacZ mutant mice,
      down-regulation of Foxn1 expression in thymic epithelial cells beginning 1 week
      after birth caused a dramatic reduction of T progenitors and an increase of B
      cell progenitors. This time point is coincident with the switch from fetal to
      adult-type hematopoietic stem cells (HSCs), which is regulated by the Lin28-Let7
      system. We hypothesize that the thymic environment might regulate this process to
      suppress fetal-type B cell development in the thymus. In this study we show that
      in the Foxn1lacZ thymus, although the down-regulation of Lin28 in thymocytes was
      normal, up-regulation of Let-7 was impaired. The failure to up-regulate Let-7
      caused a transient increase of Arid3a in B precursors, which is known to promote
      fetal-type B cell fate. Over-expression of Lin28a in HSCs also reduced Let-7 and
      promoted Arid3a expression in BM and thymic B progenitors, increasing B cell
      production in the thymus. The level of Let-7 in thymic B progenitors was up
      regulated by in vitro co-culture with IL15, Vitamin-D3, and retinoic acid, thus
      down-regulating Arid3a to promote B cell differentiation. All of these signals
      were produced in thymic epithelial cells (TECs) related to Let-7 expression in
      thymic B progenitors, and down-regulated in Foxn1lacZ mutants. Our data show that
      signals provided by TEC control thymic B cell development by up-regulating Let-7,
      suppressing Arid3a expression in intrathymic progenitor B cells to limit their
      proliferation during the neonatal to adult transition.

PMID- 29462198
TI  - Hexokinase 2 is a molecular bridge linking telomerase and autophagy.
AB  - Autophagy is systematically regulated by upstream factors and nutrients. Recent
      studies reported that telomerase and hexokinase 2 [HK2) regulate autophagy
      through mTOR and that telomerase has the capacity to bind to the HK2 promoter.
      However, the molecular linkage among telomerase, HK2, and autophagy is not fully
      understood. Here, we show that HK2 connects telomerase to autophagy. HK2
      inhibition in HepG2 cells suppressed TERT-induced autophagy activation and
      further enhancement by glucose deprivation. The HK2 downstream factor mTOR was
      responsible for the TERT-induced autophagy activation under glucose deprivation,
      implying that TERT promotes autophagy through an HK2-mTOR pathway. TERC played a
      role similar to that of TERT, and simultaneous expression of TERT and TERC
      synergistically enhanced HK2 expression and autophagy. At the gene level, TERT
      bound to the HK2 promoter at a specific region harboring the telomerase
      responsive sequence 'TTGGG.' Mutagenesis of TERC and the TERT-responsive element
      in the HK2 promoter revealed that TERC is required for the binding of TERT to the
      HK2 promoter. We demonstrate the existence of a telomerase-HK2-mTOR-autophagy
      axis and suggest that inhibition of the interaction between telomerase and the
      HK2 promoter diminishes glucose starvation-induced autophagy.

PMID- 29462199
TI  - High quality diet improves lipid metabolic profile and breeding performance in
      the blue-footed booby, a long-lived seabird.
AB  - Understanding the role of diet in the physiological condition of adults during
      reproduction and hence its effect on reproductive performance is fundamental to
      understand reproductive strategies in long-lived animals. In birds, little is
      known about the influence of the quality of food consumed at the beginning of the
      reproductive period and its short-term effects on reproductive performance. To
      assess the role of diet in the physiological condition of female blue-footed
      booby, Sula nebouxii (BFBO), during reproduction we evaluated whether individual
      differences in diet (assessed by using delta13C and delta15N values of whole
      blood from female birds and muscle tissue of the principal prey species) prior to
      egg laying and during incubation influenced their lipid metabolic profile
      (measured as triglyceride levels and C:N ratio) and their reproductive
      performance (defined by laying date, clutch size and hatching success). Females
      with higher delta15N values in their blood during the courtship and incubation
      periods had a higher lipid metabolic profile, earlier laying date, greater clutch
      size (2-3 eggs) and higher hatching success. Females that laid earlier and more
      eggs (2-3 eggs) consumed more Pacific anchoveta (Cetengraulis mysticetus) and
      Pacific thread herring (Opisthonema libertate) than did other females. These two
      prey species also had high amounts of lipids (C:N ratio) and caloric content
      (Kcal/g fresh weight). The quality of food consumed by females at the beginning
      of reproduction affected their physiological condition, as well as their short
      term reproductive performance. Our work emphasizes the importance of determining
      the influence of food quality during reproduction to understand the reproductive
      decisions and consequences in long-lived animals.

PMID- 29462200
TI  - A prophylactic multivalent vaccine against different filovirus species is
      immunogenic and provides protection from lethal infections with Ebolavirus and
      Marburgvirus species in non-human primates.
AB  - The search for a universal filovirus vaccine that provides protection against
      multiple filovirus species has been prompted by sporadic but highly lethal
      outbreaks of Ebolavirus and Marburgvirus infections. A good prophylactic vaccine
      should be able to provide protection to all known filovirus species and as an
      upside potentially protect from newly emerging virus strains. We investigated the
      immunogenicity and protection elicited by multivalent vaccines expressing
      glycoproteins (GP) from Ebola virus (EBOV), Sudan virus (SUDV), Tai Forest virus
      (TAFV) and Marburg virus (MARV). Immune responses against filovirus GP have been
      associated with protection from disease. The GP antigens were expressed by
      adenovirus serotypes 26 and 35 (Ad26 and Ad35) and modified Vaccinia virus Ankara
      (MVA) vectors, all selected for their strong immunogenicity and good safety
      profile. Using fully lethal NHP intramuscular challenge models, we assessed
      different vaccination regimens for immunogenicity and protection from filovirus
      disease. Heterologous multivalent Ad26-Ad35 prime-boost vaccination regimens
      could give full protection against MARV (range 75%-100% protection) and EBOV
      (range 50% to 100%) challenge, and partial protection (75%) against SUDV
      challenge. Heterologous multivalent Ad26-MVA prime-boost immunization gave full
      protection against EBOV challenge in a small cohort study. The use of such
      multivalent vaccines did not show overt immune interference in comparison with
      monovalent vaccines. Multivalent vaccines induced GP-specific antibody responses
      and cellular IFNgamma responses to each GP expressed by the vaccine, and cross
      reactivity to TAFV GP was detected in a trivalent vaccine expressing GP from
      EBOV, SUDV and MARV. In the EBOV challenge studies, higher humoral EBOV GP
      specific immune responses (p = 0.0004) were associated with survival from EBOV
      challenge and less so for cellular immune responses (p = 0.0320). These results
      demonstrate that it is feasible to generate a multivalent filovirus vaccine that
      can protect against lethal infection by multiple members of the filovirus family.

PMID- 29462201
TI  - Trend of estimated glomerular filtration rate during
      ombistasvir/paritaprevir/ritonavir plus dasabuvir +/- ribavirin in HIV/HCV co
      infected patients.
AB  - The renal function is a key-issue in HIV/HCV co-infected patients, nevertheless,
      it has not established so far whether HCV treatment with new direct acting agents
      could impact on estimated glomerular filtration rate (eGFR) variations. In the
      present work, we examined the real-life data on renal function that have been
      prospectively collected in the SIMIT compassionate-use program of
      ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) in 144 HIV/HCV
      genotype 1 co-infected patients. The population was 74% male, 30.5% in CDC stage
      C, with median age of 52 years (48.0-56.5) and median liver stiffness of 7.8 kPa
      (6.7-9.2). Median baseline eGFR was 102.0 (90.8-108.1), changing to 99.8 (83.5
      104.8) at the end of treatment (EoT), and 100.0 (87.3-105.6) 12 weeks after the
      EoT (FU12), p<0.0001. No patient had grade 3-4 increase of creatinine. At EoT
      60/144 (41.7%) patients had >= 5% reduction in their eGFR, confirmed at FU12 in
      39/60 (65.0%) cases. Longer duration of HCV infection (cut-off 12.9 years), lower
      HCV-RNA viral load (cut-off 1,970,160 IU/ml) and lower platelet count (cut-off
      167,000 x106/L) were significantly associated with eGFR decline at logistic
      analysis (adjOR 2.9, 95%CI 1.0-8.8, p = 0.05; adjOR 3.5, 95%CI 1.2-10.4, p =
      0.02; adjOR 2.8, 95%CI 1.1-6.8, p = 0.03, respectively). After repeating the
      analysis throughout a mixed model, a higher eGFR decline was highlighted in
      patients concomitantly treated with tenofovir (p = 0.0001), ribavirin (p =
      0.0001), or integrase inhibitors (p <0.0001), with longer duration of HIV (p =
      0.0002) and HCV infection (p = 0.035), lower baseline HCV RNA (p <0.0001),
      previous HCV treatment (p<0.0001), and older age (p<0.0001). In conclusion, our
      study confirms a good renal safety profile of OBV/PTV/r + DSV treatment in
      HIV/HCV patients, and the median decline of 2 ml/min in eGFR, albeit
      statistically significant, is of doubtful clinical significance. The role of
      aging, concomitant therapies and duration of HIV/HCV infection needs to be
      further investigated.

PMID- 29462202
TI  - Thymic B cell development is controlled by the B potential of progenitors via
      both hematopoietic-intrinsic and thymic microenvironment-intrinsic regulatory
      mechanisms.
AB  - BACKGROUND: Hematopoietic stem cells (HSCs) derived from birth through adult
      possess differing differentiation potential for T or B cell fate in the thymus;
      neonatal bone marrow (BM) cells also have a higher potential for B cell
      production in BM compared to adult HSCs. We hypothesized that this hematopoietic
      intrinsic B potential might also regulate B cell development in the thymus during
      ontogeny. METHODS: Foxn1lacZ mutant mice are a model in which down regulation of
      a thymic epithelial cell (TEC) specific transcription factor beginning one week
      postnatal causes a dramatic reduction of thymocytes production. In this study, we
      found that while T cells were decreased, the frequency of thymic B cells was
      greatly increased in these mutants in the perinatal period. We used this model to
      characterize the mechanisms in the thymus controlling B cell development.
      RESULTS: Foxn1lacZ mutants, T cell committed intrathymic progenitors (DN1a,b)
      were progressively reduced beginning one week after birth, while thymic B cells
      peaked at 3-4 weeks with pre-B-II progenitor phenotype, and originated in the
      thymus. Heterochronic chimeras showed that the capacity for thymic B cell
      production was due to a combination of higher B potential of neonatal HSCs,
      combined with a thymic microenvironment deficiency including reduction of DL4 and
      increase of IL-7 that promoted B cell fate. CONCLUSION: Our findings indicate
      that the capacity and time course for thymic B-cell production are primarily
      controlled by the hematopoietic-intrinsic potential for B cells themselves during
      ontogeny, but that signals from TECs microenvironment also influence the
      frequency and differentiation potential of B cell development in the thymus.

PMID- 29462203
TI  - A generic HTS assay for kinase screening: Validation for the isolation of an
      engineered malate kinase.
AB  - An end-point ADP/NAD+ acid/alkali assay procedure, directly applicable to library
      screening of any type of ATP-utilising/ADP producing enzyme activity, was
      implemented. Typically, ADP production is coupled to NAD+ co-enzyme formation by
      the conventional addition of pyruvate kinase and lactate dehydrogenase.
      Transformation of enzymatically generated NAD+ into a photometrically active
      alkali derivative product is then achieved through the successive application of
      acidic/alkali treatment steps. The assay was successfully miniaturized to search
      for malate kinase activity in a structurally-guided library of LysC aspartate
      kinase variants comprising 6,700 clones. The screening procedure enabled the
      isolation of nine positive variants showing novel kinase activity on (L)-malate,
      the best mutant, LysC V115A:E119S:E434V exhibited strong substrate selectivity
      for (L)-malate compared to (L)-aspartate with a
      (kcat/Km)malate/(kcat/Km)aspartate ratio of 86. Double mutants V115A:E119S,
      V115A:E119C and E119S:E434V were constructed to further probe the origins of
      stabilising substrate binding energy gains for (L)-malate due to mutation. The
      introduction of less sterically hindering side-chains in engineered enzymes
      carrying E119S and V115A mutations increases the effective volume available for
      substrate binding in the catalytic pocket. Improved binding of the (L)-malate
      substrate may be assisted by less hindered movement of the Phe184 aromatic side
      chain. Additional favourable long-range electostatic effects on binding arising
      from the E434V surface mutation are conditionally dependent upon the presence of
      the V115A mutation close to Phe184 in the active-site.

PMID- 29462204
TI  - Microbial diversity and component variation in Xiaguan Tuo Tea during pile
      fermentation.
AB  - Xiaguan Tuo Tea is largely consumed by the Chinese, but there is little research
      into the microbial diversity and component changes during the fermentation of
      this tea. In this study, we first used fluorescence in situ hybridization (FISH),
      next-generation sequencing (NGS) and chemical analysis methods to determine the
      microbial abundance and diversity and the chemical composition during
      fermentation. The FISH results showed that the total number of microorganisms
      ranges from 2.3*102 to 4.0*108 cells per gram of sample during fermentation and
      is mainly dominated by fungi. In the early fermentation stages, molds are
      dominant (0.6*102~2.8*106 cells/g, 0~35 d). However, in the late stages of
      fermentation, yeasts are dominant (3.6*104~9.6*106 cells/g, 35~56 d). The
      bacteria have little effect during the fermentation of tea (102~103 cells/g, <1%
      of fungus values). Of these fungi, A. niger (Aspergillus niger) and B.
      adeninivorans (Blastobotrys adeninivorans) are identified as the two most common
      strains, based on Next-generation Sequencing (NGS) analysis. Peak diversity in
      tea was observed at day 35 of fermentation (Shannon-Weaver index: 1.195857), and
      lower diversity was observed on days 6 and 56 of fermentation (Shannon-Weaver
      index 0.860589 and 1.119106, respectively). During the microbial fermentation,
      compared to the unfermented tea, the tea polyphenol content decreased by 54%, and
      the caffeine content increased by 59%. Theanine and free amino acid contents were
      reduced during fermentation by 81.1 and 92.85%, respectively.

PMID- 29462205
TI  - Spatial analysis of ecosystem service relationships to improve targeting of
      payments for hydrological services.
AB  - Payment for hydrological services (PHS) are popular tools for conserving
      ecosystems and their water-related services. However, improving the spatial
      targeting and impacts of PHS, as well as their ability to foster synergies with
      other ecosystem services (ES), remain challenging. We aimed at using spatial
      analyses to evaluate the targeting performance of Mexico's National PHS program
      in central Veracruz. We quantified the effectiveness of areas targeted for PHS in
      actually covering areas of high HS provision and social priority during 2003
      2013. First, we quantified provisioning and spatial distributions of two target
      (water yield and soil retention), and one non-target ES (carbon storage) using
      InVEST. Subsequently, pairwise relationships among ES were quantified by using
      spatial correlation and overlap analyses. Finally, we evaluated targeting by: (i)
      prioritizing areas of individual and overlapping ES; (ii) quantifying spatial co
      occurrences of these priority areas with those targeted by PHS; (iii) evaluating
      the extent to which PHS directly contribute to HS delivery; and (iv), testing if
      PHS targeted areas disproportionately covered areas with high ecological and
      social priority. We found that modelled priority areas exhibited non-random
      distributions and distinct spatial patterns. Our results show significant
      pairwise correlations between all ES suggesting synergistic relationships.
      However, our analysis showed a significantly lower overlap than expected and thus
      significant mismatches between PHS targeted areas and all types of priority
      areas. These findings suggest that the targeting of areas with high HS
      provisioning and social priority by Mexico's PHS program could be improved
      significantly. This study underscores: (1) the importance of using maps of HS
      provisioning as main targeting criteria in PHS design to channel payments towards
      areas that require future conservation, and (2) the need for future research that
      helps balance ecological and socioeconomic targeting criteria.

PMID- 29462206
TI  - Cell-free synthesis of functional antibody fragments to provide a structural
      basis for antibody-antigen interaction.
AB  - Growing numbers of therapeutic antibodies offer excellent treatment strategies
      for many diseases. Elucidation of the interaction between a potential therapeutic
      antibody and its target protein by structural analysis reveals the mechanism of
      action and offers useful information for developing rational antibody designs for
      improved affinity. Here, we developed a rapid, high-yield cell-free system using
      dialysis mode to synthesize antibody fragments for the structural analysis of
      antibody-antigen complexes. Optimal synthesis conditions of fragments (Fv and
      Fab) of the anti-EGFR antibody 059-152 were rapidly determined in a day by using
      a 30-MUl-scale unit. The concentration of supplemented disulfide isomerase, DsbC,
      was critical to obtaining soluble antibody fragments. The optimal conditions were
      directly applicable to a 9-ml-scale reaction, with linear scalable yields of more
      than 1 mg/ml. Analyses of purified 059-152-Fv and Fab showed that the cell-free
      synthesized antibody fragments were disulfide-bridged, with antigen binding
      activity comparable to that of clinical antibodies. Examination of the crystal
      structure of cell-free synthesized 059-152-Fv in complex with the extracellular
      domain of human EGFR revealed that the epitope of 059-152-Fv broadly covers the
      EGF binding surface on domain III, including residues that formed critical
      hydrogen bonds with EGF (Asp355EGFR, Gln384EGFR, H409EGFR, and Lys465EGFR), so
      that the antibody inhibited EGFR activation. We further demonstrated the
      application of the cell-free system to site-specific integration of non-natural
      amino acids for antibody engineering, which would expand the availability of
      therapeutic antibodies based on structural information and rational design. This
      cell-free system could be an ideal antibody-fragment production platform for
      functional and structural analysis of potential therapeutic antibodies and for
      engineered antibody development.

PMID- 29462207
TI  - Karyotype evolution in Phalaris (Poaceae): The role of reductional dysploidy,
      polyploidy and chromosome alteration in a wide-spread and diverse genus.
AB  - Karyotype characteristics can provide valuable information on genome evolution
      and speciation, in particular in taxa with varying basic chromosome numbers and
      ploidy levels. Due to its worldwide distribution, remarkable variability in
      morphological traits and the fact that ploidy change plays a key role in its
      evolution, the canary grass genus Phalaris (Poaceae) is an excellent study system
      to investigate the role of chromosomal changes in species diversification and
      expansion. Phalaris comprises diploid species with two basic chromosome numbers
      of x = 6 and 7 as well as polyploids based on x = 7. To identify distinct
      karyotype structures and to trace chromosome evolution within the genus, we apply
      fluorescence in situ hybridisation (FISH) of 5S and 45S rDNA probes in four
      diploid and four tetraploid Phalaris species of both basic numbers. The data
      agree with a dysploid reduction from x = 7 to x = 6 as the result of reciprocal
      translocations between three chromosomes of an ancestor with a diploid chromosome
      complement of 2n = 14. We recognize three different genomes in the genus: (1) the
      exclusively Mediterranean genome A based on x = 6, (2) the cosmopolitan genome B
      based on x = 7 and (3) a genome C based on x = 7 and with a distribution in the
      Mediterranean and the Middle East. Both auto- and allopolyploidy of genomes B and
      C are suggested for the formation of tetraploids. The chromosomal divergence
      observed in Phalaris can be explained by the occurrence of dysploidy, the
      emergence of three different genomes, and the chromosome rearrangements
      accompanied by karyotype change and polyploidization. Mapping the recognized
      karyotypes on the existing phylogenetic tree suggests that genomes A and C are
      restricted to sections Phalaris and Bulbophalaris, respectively, while genome B
      occurs across all taxa with x = 7.

PMID- 29462208
TI  - Quantifying the fitness cost of HIV-1 drug resistance mutations through
      phylodynamics.
AB  - Drug resistant HIV is a major threat to the long-term efficacy of antiretroviral
      treatment. Around 10% of ART-naive patients in Europe are infected with drug
      resistant HIV type 1. Hence it is important to understand the dynamics of
      transmitted drug resistance evolution. Thanks to routinely performed drug
      resistance tests, HIV sequence data is increasingly available and can be used to
      reconstruct the phylogenetic relationship among viral lineages. In this study we
      employ a phylodynamic approach to quantify the fitness costs of major resistance
      mutations in the Swiss HIV cohort. The viral phylogeny reflects the transmission
      tree, which we model using stochastic birth-death-sampling processes with two
      types: hosts infected by a sensitive or resistant strain. This allows
      quantification of fitness cost as the ratio between transmission rates of hosts
      infected by drug resistant strains and transmission rates of hosts infected by
      drug sensitive strains. The resistance mutations 41L, 67N, 70R, 184V, 210W, 215D,
      215S and 219Q (nRTI-related) and 103N, 108I, 138A, 181C, 190A (NNRTI-related) in
      the reverse trancriptase and the 90M mutation in the protease gene are included
      in this study. Among the considered resistance mutations, only the 90M mutation
      in the protease gene was found to have significantly higher fitness than the drug
      sensitive strains. The following mutations associated with resistance to reverse
      transcriptase inhibitors were found to be less fit than the sensitive strains:
      67N, 70R, 184V, 219Q. The highest posterior density intervals of the transmission
      ratios for the remaining resistance mutations included in this study all included
      1, suggesting that these mutations do not have a significant effect on viral
      transmissibility within the Swiss HIV cohort. These patterns are consistent with
      alternative measures of the fitness cost of resistance mutations. Overall, we
      have developed and validated a novel phylodynamic approach to estimate the
      transmission fitness cost of drug resistance mutations.

PMID- 29462209
TI  - Modulation of the colon cancer cell phenotype by pro-inflammatory macrophages: A
      preclinical model of surgery-associated inflammation and tumor recurrence.
AB  - Peritoneal infection after colorectal cancer surgery is associated with a higher
      rate of tumor relapse. We have recently proposed that soluble inflammatory
      factors released in response to a postoperative infection enhance tumor
      progression features in residual tumor cells. In an effort to set up models to
      study the mechanisms of residual tumor cell activation during surgery-associated
      inflammation, we have analyzed the phenotypic response of colon cancer cell lines
      to the paracrine effects of THP-1 and U937 differentiated human macrophages,
      which release an inflammatory medium characteristic of an innate immune response.
      The exposure of the colon cancer cell lines HT-29 and SW620 to conditioned media
      isolated from differentiated THP-1 and U937 macrophages induced a mesenchymal
      like phenotypic shift, involving the activation of in vitro invasiveness. The
      inflammatory media activated the beta-catenin/TCF4 transcriptional pathway and
      induced the expression of several mesenchymal (e.g., FN1 and VIM) and TCF4 target
      genes (e.g., MMP7, PTGS2, MET, and CCD1). Similarly, differential expression of
      some transcription factors involved in epithelial-to-mesenchymal transitions
      (i.e. ZEB1, SNAI1, and SNAI2) was variably observed in the colon cancer cell
      lines when exposed to the inflammatory media. THP-1 and U937 macrophages, which
      displayed characteristics of M1 differentiation, overexpressed some cytokines
      previously shown to be induced in colorectal cancer patients with increased rates
      of tumor recurrence associated with postoperative peritoneal infections, thus
      suggesting their pro-tumoral character. Therefore, the environment created by
      inflammatory M1 macrophages enhances features of epithelial-to-mesenchymal
      transition, and may be useful as a model to characterize pro-inflammatory
      cytokines as putative biomarkers of tumor recurrence risk.

PMID- 29462210
TI  - SNP markers tightly linked to root knot nematode resistance in grapevine (Vitis
      cinerea) identified by a genotyping-by-sequencing approach followed by Sequenom
      MassARRAY validation.
AB  - Plant parasitic nematodes, including root knot nematode Meloidogyne species,
      cause extensive damage to agriculture and horticultural crops. As Vitis vinifera
      cultivars are susceptible to root knot nematode parasitism, rootstocks resistant
      to these soil pests provide a sustainable approach to maintain grapevine
      production. Currently, most of the commercially available root knot nematode
      resistant rootstocks are highly vigorous and take up excess potassium, which
      reduces wine quality. As a result, there is a pressing need to breed new root
      knot nematode resistant rootstocks, which have no impact on wine quality. To
      develop molecular markers that predict root knot nematode resistance for marker
      assisted breeding, a genetic approach was employed to identify a root knot
      nematode resistance locus in grapevine. To this end, a Meloidogyne javanica
      resistant Vitis cinerea accession was crossed to a susceptible Vitis vinifera
      cultivar Riesling and results from screening the F1 individuals support a model
      that root knot nematode resistance, is conferred by a single dominant allele,
      referred as MELOIDOGYNE JAVANICA RESISTANCE1 (MJR1). Further, MJR1 resistance
      appears to be mediated by a hypersensitive response that occurs in the root
      apical meristem. Single nucleotide polymorphisms (SNPs) were identified using
      genotyping-by-sequencing and results from association and genetic mapping
      identified the MJR1 locus, which is located on chromosome 18 in the Vitis cinerea
      accession. Validation of the SNPs linked to the MJR1 locus using a Sequenom
      MassARRAY platform found that only 50% could be validated. The validated SNPs
      that flank and co-segregate with the MJR1 locus can be used for marker-assisted
      selection for Meloidogyne javanica resistance in grapevine.

PMID- 29462211
TI  - Lung cancer and socioeconomic status in a pooled analysis of case-control
      studies.
AB  - BACKGROUND: An association between low socioeconomic status (SES) and lung cancer
      has been observed in several studies, but often without adequate control for
      smoking behavior. We studied the association between lung cancer and
      occupationally derived SES, using data from the international pooled SYNERGY
      study. METHODS: Twelve case-control studies from Europe and Canada were included
      in the analysis. Based on occupational histories of study participants we
      measured SES using the International Socio-Economic Index of Occupational Status
      (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI
      range into categories, using various criteria. Stratifying by gender, we
      calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional
      logistic regression, adjusting for age, study, and smoking behavior. We conducted
      analyses by histological subtypes of lung cancer and subgroup analyses by study
      region, birth cohort, education and occupational exposure to known lung
      carcinogens. RESULTS: The analysis dataset included 17,021 cases and 20,885
      controls. There was a strong elevated OR between lung cancer and low SES, which
      was attenuated substantially after adjustment for smoking, however a social
      gradient persisted. SES differences in lung cancer risk were higher among men
      (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53
      (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR
      1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)). CONCLUSION: SES
      remained a risk factor for lung cancer after adjustment for smoking behavior.

PMID- 29462212
TI  - Epstein-Barr virus nuclear antigen EBNA-LP is essential for transforming naive B
      cells, and facilitates recruitment of transcription factors to the viral genome.
AB  - The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is the
      first viral latency-associated protein produced after EBV infection of resting B
      cells. Its role in B cell transformation is poorly defined, but it has been
      reported to enhance gene activation by the EBV protein EBNA2 in vitro. We
      generated EBNA-LP knockout (LPKO) EBVs containing a STOP codon within each repeat
      unit of internal repeat 1 (IR1). EBNA-LP-mutant EBVs established lymphoblastoid
      cell lines (LCLs) from adult B cells at reduced efficiency, but not from
      umbilical cord B cells, which died approximately two weeks after infection. Adult
      B cells only established EBNA-LP-null LCLs with a memory (CD27+) phenotype.
      Quantitative PCR analysis of virus gene expression after infection identified
      both an altered ratio of the EBNA genes, and a dramatic reduction in transcript
      levels of both EBNA2-regulated virus genes (LMP1 and LMP2) and the EBNA2
      independent EBER genes in the first 2 weeks. By 30 days post infection, LPKO
      transcription was the same as wild-type EBV. In contrast, EBNA2-regulated
      cellular genes were induced efficiently by LPKO viruses. Chromatin
      immunoprecipitation revealed that EBNA2 and the host transcription factors EBF1
      and RBPJ were delayed in their recruitment to all viral latency promoters tested,
      whereas these same factors were recruited efficiently to several host genes,
      which exhibited increased EBNA2 recruitment. We conclude that EBNA-LP does not
      simply co-operate with EBNA2 in activating gene transcription, but rather
      facilitates the recruitment of several transcription factors to the viral genome,
      to enable transcription of virus latency genes. Additionally, our findings
      suggest that EBNA-LP is essential for the survival of EBV-infected naive B cells.

PMID- 29462213
TI  - Early detection of pancreatic cancer in mouse models using a novel antibody,
      TAB004.
AB  - Pancreatic ductal adenocarcinoma (PDA) is the fourth-leading cause of cancer
      death in the United States with a 5-year overall survival rate of 8% for all
      stages combined. But this decreases to 3% for the majority of patients that
      present with stage IV PDA at time of diagnosis. The lack of distinct early
      symptoms for PDA is one of the primary reasons for the late diagnosis. Common
      symptoms like weight loss, abdominal and back pains, and jaundice are often
      mistaken for symptoms of other issues and do not appear until the cancer has
      progressed to a late stage. Thus the development of novel imaging platforms for
      PDA is crucial for the early detection of the disease. MUC1 is a tumor-associated
      antigen (tMUC1) expressed on 80% of PDA. The goal of this study was to determine
      the targeting and detection capabilities of a tMUC1 specific antibody, TAB004.
      TAB004 antibody conjugated to a near infrared fluorescent probe was injected
      intraperitoneally into immune competent orthotopic and spontaneous models of PDA.
      Results show that fluorophore conjugated TAB004 specifically targets a) 1 week
      old small tumor in the pancreas in an orthotopic PDA model and b) very early pre
      neoplastic lesions (PanIN lesions) that develop in the spontaneous PDA model
      before progression to adenocarcinoma. Thus, TAB004 is a promising antibody to
      deliver imaging agents directly to the pancreatic tumor microenvironment,
      significantly affecting early detection of PDA.

PMID- 29462214
TI  - A phytosociological analysis and description of wetland vegetation and ecological
      factors associated with locations of high mortality for the 2010-11 Rift Valley
      fever outbreak in South Africa.
AB  - Rift Valley fever (RVF) is endemic in Africa and parts of the Middle East. It is
      an emerging zoonotic disease threat to veterinary and public health. Outbreaks of
      the disease have severe socio-economic impacts. RVF virus emergence is closely
      associated with specific endorheic wetlands that are utilized by the virus'
      mosquito vectors. Limited botanical vegetation surveys had been published with
      regard to RVF virus (RVFV) ecology. We report on a phytosociological
      classification, analysis and description of wetland vegetation and related
      abiotic parameters to elucidate factors possibly associated with the 2010-2011
      RVFV disease outbreak in South Africa. The study sites were located in the
      western Free State and adjacent Northern Cape covering an area of ~40,000 km2
      with wetlands associated with high RVF mortality rates in livestock. Other study
      sites included areas where no RVF activity was reported during the 2010-11 RVF
      outbreak. A total of 129 plots (30 m2) were selected where a visible difference
      could be seen in the wetland and upland vegetation. The Braun-Blanquet method was
      used for plant sampling. Classification was done using modified Two-Way Indicator
      Species Analysis. The vegetation analysis resulted in the identification of eight
      plant communities, seven sub-communities and two variants. Indirect ordination
      was carried out using CANOCO to investigate the relationship between species and
      wetland ecology. The study also identified 5 categories of wetlands including
      anthropogenic wetlands. Locations of reported RVF cases overlapped sites
      characterized by high clay-content soils and specific wetland vegetation. These
      findings indicate ecological and environmental parameters that represent
      preferred breeding habitat for RVFV competent mosquito vectors.

PMID- 29462215
TI  - Robson 10-groups classification system to access C-section in two public
      hospitals of the Federal District/Brazil.
AB  - BACKGROUND: The global increase in C-section rates is real. In Brazil, these
      indices correspond to 58.94% in the Midwest region and 52.77% in the Federal
      District. OBJECTIVE: To evaluate the C-section rates and identify the groups with
      the greatest risk at two reference hospitals in the public network of Federal
      District/Brazil, using 10-Group Robson System. METHOD: A cross-sectional study of
      6579 births assisted at the Hospital A (HA) and the Hospital B (HB) during 2013.
      The C-section rates in each group and its respective contribution to the total
      hospital C-sections was compared between HA and HB. To this, was used the
      proportion difference test (similar to chi-square test), with RR and 95% CI, and
      the logistic regression analysis (OR; 95% CI) among the groups with higher C
      section/total C-section. The significance limit of p < 0.05 was defined for all
      tests. RESULTS: The C-section rates were 50.8% at the HA and 42.3% at the HB,
      with 1.20 RR (95%CI = 1.13-1.28) at the HA. The highest rates were observed in
      Robson groups G5, G1, and G2. At the HA, G1 had a 21.5% C-section rate, which was
      greater than at the HB (13.8%; p < 0.05); the cesarean rates for groups G2 and G5
      were higher at the HB (respectively, 18.6 and 38.1%) than at the HA (14.8 and
      32.5%, respectively; p < 0.05). CONCLUSION: These results point out specific
      goals to be achieved in order to reduce abusive cesarean rates in both A and B
      hospitals, especially in the primigravida and in those with previous C-section.

PMID- 29462216
TI  - A hybrid gene selection approach to create the S1500+ targeted gene sets for use
      in high-throughput transcriptomics.
AB  - Changes in gene expression can help reveal the mechanisms of disease processes
      and the mode of action for toxicities and adverse effects on cellular responses
      induced by exposures to chemicals, drugs and environment agents. The U.S. Tox21
      Federal collaboration, which currently quantifies the biological effects of
      nearly 10,000 chemicals via quantitative high-throughput screening(qHTS) in in
      vitro model systems, is now making an effort to incorporate gene expression
      profiling into the existing battery of assays. Whole transcriptome analyses
      performed on large numbers of samples using microarrays or RNA-Seq is currently
      cost-prohibitive. Accordingly, the Tox21 Program is pursuing a high-throughput
      transcriptomics (HTT) method that focuses on the targeted detection of gene
      expression for a carefully selected subset of the transcriptome that potentially
      can reduce the cost by a factor of 10-fold, allowing for the analysis of larger
      numbers of samples. To identify the optimal transcriptome subset, genes were
      sought that are (1) representative of the highly diverse biological space, (2)
      capable of serving as a proxy for expression changes in unmeasured genes, and (3)
      sufficient to provide coverage of well described biological pathways. A hybrid
      method for gene selection is presented herein that combines data-driven and
      knowledge-driven concepts into one cohesive method. Our approach is modular,
      applicable to any species, and facilitates a robust, quantitative evaluation of
      performance. In particular, we were able to perform gene selection such that the
      resulting set of "sentinel genes" adequately represents all known canonical
      pathways from Molecular Signature Database (MSigDB v4.0) and can be used to infer
      expression changes for the remainder of the transcriptome. The resulting
      computational model allowed us to choose a purely data-driven subset of 1500
      sentinel genes, referred to as the S1500 set, which was then augmented using a
      knowledge-driven selection of additional genes to create the final S1500+ gene
      set. Our results indicate that the sentinel genes selected can be used to
      accurately predict pathway perturbations and biological relationships for samples
      under study.

PMID- 29462218
TI  - Erratum: Local environmental quality positively predicts breastfeeding in the
      UK's Millennium Cohort Study.
AB  - [This corrects the article DOI: 10.1093/emph/eox011.][This corrects the article
      DOI: 10.1093/emph/eox011.].

PMID- 29462217
TI  - A flocking algorithm for multi-agent systems with connectivity preservation under
      hybrid metric-topological interactions.
AB  - In this paper, we propose a connectivity-preserving flocking algorithm for multi
      agent systems in which the neighbor set of each agent is determined by the hybrid
      metric-topological distance so that the interaction topology can be represented
      as the range-limited Delaunay graph, which combines the properties of the
      commonly used disk graph and Delaunay graph. As a result, the proposed flocking
      algorithm has the following advantages over the existing ones. First, range
      limited Delaunay graph is sparser than the disk graph so that the information
      exchange among agents is reduced significantly. Second, some links irrelevant to
      the connectivity can be dynamically deleted during the evolution of the system.
      Thus, the proposed flocking algorithm is more flexible than existing algorithms,
      where links are not allowed to be disconnected once they are created. Finally,
      the multi-agent system spontaneously generates a regular quasi-lattice formation
      without imposing the constraint on the ratio of the sensing range of the agent to
      the desired distance between two adjacent agents. With the interaction topology
      induced by the hybrid distance, the proposed flocking algorithm can still be
      implemented in a distributed manner. We prove that the proposed flocking
      algorithm can steer the multi-agent system to a stable flocking motion, provided
      the initial interaction topology of multi-agent systems is connected and the
      hysteresis in link addition is smaller than a derived upper bound. The
      correctness and effectiveness of the proposed algorithm are verified by extensive
      numerical simulations, where the flocking algorithms based on the disk and
      Delaunay graph are compared.

PMID- 29462220
TI  - Trends in Atopic Dermatitis Management: Comparison of 1990-1997 to 2003-2012.
AB  - BACKGROUND: Atopic dermatitis (AD) is primarily treated with topical therapies,
      systemic immunosuppressants, or adjunctive therapies. OBJECTIVE: As novel
      treatment approaches for AD emerge, we characterize AD treatment and examine
      trends in treatment over time. METHODS: Visits for AD were identified in the 2003
      2012 National Ambulatory Medical Care Survey (NAMCS). We identified topical
      corticosteroids (TCS), antibiotics (Abx), antihistamines (AH), topical
      calcineurin inhibitors (TCI), and systemic immunosuppressants (SI) prescribed at
      AD visits. RESULTS: There were 990,000 annual visits for AD from 2003-2012 (3.2
      visits/1000 people/year). TCS were the most frequently used medication (59% of
      visits). Topical calcineurin inhibitors (TCI) were the second most prescribed
      medication for AD among dermatologists (23% of visits), while antihistamines were
      second among all other physicians (16-44% of visits). Unlike other medications,
      use of TCIs decreased over time. LIMITATIONS: The NAMCS does not follow
      individual patients over time. CONCLUSIONS: TCI use has been decreasing. New
      topical AD treatments may provide an alternative to TCS, better treatment
      outcomes for moderate-to-severe atopic dermatitis, and an alternative to systemic
      antihistamines whose efficacy in AD is unproven and whose general use in AD
      management is discouraged by the American Academy of Dermatology. J Drugs
      Dermatol. 2018;17(2):135-140.

PMID- 29462221
TI  - Vismodegib Use in Clinical Practice: Analysis of a United States Medical Claims
      Database.
AB  - BACKGROUND: Information is limited on the use of vismodegib for treatment of
      advanced basal cell carcinoma beyond the setting of clinical trials. OBJECTIVE:
      To investigate the treatment patterns and characteristics of patients treated
      with vismodegib in clinical practice. METHODS: A longitudinal, retrospective
      cohort study was undertaken using data from a US commercial insurance claims
      (Truven Health Analytics MarketScan) database. Eligible patients were >=18 years
      of age, with >=1 claim for vismodegib from January 2012 to December 2015.
      RESULTS: A total of 321 patients were included in the analysis. Approximately 20%
      of the patients took 1 or more treatment breaks of >= 30 days each before
      treatment discontinuation. Median duration of vismodegib treatment before the
      first treatment break and discontinuation was 4.0 and 5.5 months, respectively.
      Older age ( > 65 years) and absence of Gorlin syndrome were associated with
      increased risk for treatment interruption or discontinuation. Overall, 47% and
      36% of patients underwent surgery or radiotherapy within the 6 months before and
      after vismodegib initiation, respectively. CONCLUSIONS: Real-world evidence
      indicates that vismodegib is being used in clinical practice as part of
      combination treatment strategies. J Drugs Dermatol. 2018;17(2):143-148.

PMID- 29462222
TI  - Cross-Sectional Survey of the Burden of Illness of Rosacea by Erythema Severity.
AB  - Rosacea is a chronic skin condition characterized by persistent central facial
      erythema. To explore the burden of illness of rosacea in US adults, a cross
      sectional web-based survey was conducted. Participants answered questions on
      sociodemographics, clinical characteristics, bothersome symptoms, coping and
      avoidance behaviors, self-perceptions, and health care resource utilization, and
      completed 2 quality of life instruments, the 21-item rosacea-specific quality of
      life questionnaire (RosaQoL) and the 36-item Short Form Health Survey (SF-36).
      This paper reports the data from the 409 respondents with
      erythematotelangiectatic rosacea (ETR), analyzed by erythema severity. Mean age
      was 53.1 years; mild, moderate, or severe erythema was reported by 63.6%, 32.0%,
      and 4.4% of participants, respectively. Blushing/flushing and bumps/pustules were
      the most bothersome symptoms across severity subgroups. Participants in all
      subgroups coped with rosacea by applying make-up and managing their stress and
      anxiety, and tried to prevent rosacea flares by avoiding sun exposure, specific
      skin care products, and other triggers. Self-perceptions differed by severity
      subgroup: satisfaction with facial appearance significantly decreased, and
      worrying about how people will react and feelings of unattractiveness to others
      significantly increased, with greater erythema severity (all P less than 0.01).
      Treatment or assessment of rosacea was sought by 20% of participants in the past
      3 months, most commonly from a dermatologist. Metronidazole was the most
      frequently prescribed topical product across severity subgroups, whereas
      doxycycline and other oral antibiotics were prescribed most frequently in the
      severe erythema subgroup. RosaQoL emotional domain scores increased with erythema
      severity (P equals 0.0035), but none of the SF-36 domain scores differed
      significantly by erythema severity. These results demonstrate that rosacea is
      associated with a substantial burden of illness that spans all levels of erythema
      severity in patients with ETR. Feelings of unattractiveness and the adverse
      impact of rosacea on emotional quality of life increased with erythema severity.
      J Drugs Dermatol. 2018;17(2):150-158.

PMID- 29462223
TI  - Efficacy, Safety, and Tolerability of Topical Dapsone Gel, 7.5% for Treatment of
      Acne Vulgaris by Fitzpatrick Skin Phototype.
AB  - BACKGROUND: Acne vulgaris (acne) is prevalent in individuals with skin of color,
      often with more frequent sequelae than in patients with lighter skin color. It is
      important to determine if there are also differences in response to medications.
      OBJECTIVE: This study evaluated the efficacy and tolerability of once-daily
      dapsone gel, 7.5% in patients with acne, stratified by Fitzpatrick skin
      phototype. METHODS: Data were pooled from 2 identically designed, phase 3,
      randomized, double-blind, vehicle-controlled studies in patients aged 12 years
      and older with moderate acne. Patients applied dapsone gel, 7.5% or vehicle once
      daily for 12 weeks. Efficacy was evaluated using the Global Acne Assessment Score
      (GAAS), lesion counts, and Acne Symptom and Impact Scale (ASIS); adverse events
      (AEs) and tolerability were also assessed. RESULTS: This analysis included 2216
      patients with skin phototypes I-III and 2111 with types IV-VI. Dapsone gel, 7.5%
      significantly improved acne severity versus vehicle in both skin phototype
      subgroups, as determined by the percentage of patients with at least a 1-grade
      improvement in GAAS and mean change from baseline in GAAS (both, P less than
      .0001) at week 12 versus baseline. Dapsone gel, 7.5% significantly reduced
      inflammatory, comedonal, and total lesions in skin phototypes I-III (P less than
      .001) and IV-VI (P less than equal to .01) versus vehicle. Improvements in
      inflammatory lesions occurred first, with generally similar patterns of
      improvement seen over time in GAAS, comedonal lesions, and ASIS domains. The
      incidence of AEs was similar in both skin phototype subgroups and between study
      medications. Local scaling, erythema, stinging/burning, and dryness were rated
      "none" by most patients in both treatment groups and skin phototype subgroups.
      CONCLUSION: Once-daily dapsone gel, 7.5% was effective, safe, and well tolerated
      in patients with all skin phototypes who were treated for moderate acne. J Drugs
      Dermatol. 2018;17(2):160-167.

PMID- 29462224
TI  - Planimetric Post-hoc Analysis of Women With Onychomycosis from Tavaborole 5%
      Phase III Studies: Evidence of Greater Improvements in Patients With >50%
      Baseline Infection.
AB  - Women with onychomycosis may suffer more effects on their quality of life than
      men. There is limited female-specific data on the treatment of onychomycosis.
      Tavaborole is a topical treatment option for onychomycosis. This post-hoc study
      evaluated the nail plates of women using data from the tavaborole 5% Phase III
      studies at baseline and end of study for the areas of healthy nail and infected
      nail. Over 52 weeks (48-week treatment, 4-week follow up), women treated with
      tavaborole had an average 32% increase in healthy nail and 21% decrease in
      infected nail. Patients with baseline infection involving >50% of the nail plate
      had an average increase in percentage of unaffected nail surface area of 81% and
      a corresponding 51% decrease in infected nail. These analyses suggest that
      patients with the greatest toenail involvement at baseline had greater overall
      improvements than those who were less affected. This evaluation provides
      additional clinical guidance for treating women with onychomycosis using
      tavaborole. J Drugs Dermatol. 2018;17(2):168-172.

PMID- 29462225
TI  - Is Severity of Disease a Prognostic Factor for Cure Following Treatment of
      Onychomycosis?
AB  - BACKGROUND: Onychomycosis is a common disease that remains a difficult disorder
      to treat despite the introduction of new topical agents; and not all patients are
      cured. Clinical experience leads us to suggest a number of host-related factors
      can affect the chance of cure, but studies supporting these observations are
      currently lacking. Although many studies, particularly on topical agents, rely on
      severity classification when selecting patients for inclusion, a pilot study was
      unable to demonstrate any prognostic value of the extension of nail involvement.
      In addition, no universal severity classification exists, and most studies do not
      report prognostic factors. OBJECTIVE: To investigate the efficacy of
      efinaconazole topical solution, 10% in patients with mild-to-moderate
      onychomycosis and determine the impact of baseline severity on treatment outcome.
      METHODS: Post hoc pooled analysis of two identical, multicenter, randomized,
      double-blind, vehicle-controlled studies in 1655 patients aged 18-70 years with a
      clinical and mycological diagnosis of mild-to-moderate dermatophyte toenail
      onychomycosis (20-50% clinical involvement). Patients were randomized (3:1) to
      efinaconazole 10% solution or vehicle, once-daily for 48 weeks, with 4-week post
      treatment follow-up. Efficacy criteria included clear nail (0% target nail plate
      involvement), almost clear nail (<=5% target nail plate involvement), and
      clinical treatment success (<=10% target nail plate involvement) at week 52. For
      the post hoc analysis, patients were classified as mild (20%-29% nail
      involvement), moderate (30%-39%), and moderately severe (40%-50%) at baseline.
      RESULTS: Overall, 25%, 23%, and 52% of patients had mild, moderate, or moderately
      severe disease at baseline. Baseline nail involvement did not appear to predict
      treatment outcomes. The proportion of patients with mild disease who had a clear
      nail progressively reduced by week 36 (58%) and week 48 (41%), and even further
      by week 52 (37%). Of the 237 patients treated with efinaconazole who were 'clear'
      at week 52, 37%, 24%, and 39% had mild, moderate or moderately severe disease
      respectively at baseline. The majority of patients (N=634) saw at least a 50%
      improvement in their target toenail by week 52. Almost half of these patients
      (N=312, 49.2%) were moderately severe at baseline. CONCLUSIONS: This post hoc
      analysis supports previous data showing good efficacy of efinaconazole in mild
      onychomycosis. The relative contribution to overall efficacy results at week 52
      of patients with moderate or moderately severe disease was unexpected for a
      topical therapy, and warrants further study, especially as they represent the
      majority of patients enrolled in the two studies. It is possible that comparable
      efficacy can be achieved in these more severe patients with longer treatment
      courses, or follow-up. J Drugs Dermatol. 2018;17(2):175-178.

PMID- 29462226
TI  - Increased Prevalence of Cancer in Adult Patients With Psoriasis in the United
      States: A Claims Based Analysis.
AB  - BACKGROUND: Psoriasis (Ps) is a chronic inflammatory immune-mediated skin disease
      that has been identified as a risk factor for various conditions including
      neoplasms. OBJECTIVE: To compare prevalence of cancer between Ps and Ps-free
      patients. METHODS: Adult patients continuously enrolled for >=12 months (>=1
      month in 2014) were selected from a large United States (US) claims database
      (Q1:2010-Q4:2014) and classified as Ps patients (>=2 Ps diagnoses; International
      Classification of Diseases 9th Revision, [ICD-9] code: 696.1x) and Ps-free
      patients (no Ps diagnosis). Patients were exactly matched (1:1) based on age,
      gender, state of residence, and insurance plan type. Prevalence of cancer was
      compared between cohorts over patients' last 12 months of continuous healthcare
      plan enrollment using logistic-regression models. RESULTS: A total of 179,066
      pairs of Ps and Ps-free patients were selected. Median age was 54.0 years, 51.7%
      were females. Prevalence of cancer was higher among Ps patients for any type of
      neoplasms (OR [95% confidence interval (CI)]=1.86 [1.83; 1.89]), malignant
      neoplasms (OR [95% CI]=1.53 [1.49;1.57]), as well as malignant skin neoplasms (OR
      [95% CI]=1.87 [1.79; 1.95]), lymphatic and hematopoietic tissues (OR [95%
      CI]=1.70 [1.57;1.84]), genital (OR [95% CI]=1.33 [1.26;1.41]), breast (OR [95%
      CI]=1.32 [1.24;1.40]), digestive organs and peritoneum (OR [95% CI]=1.24
      [1.13;1.35]), urinary organs (OR [95% CI]=1.49 [1.36;1.64]), respiratory and
      intrathoracic organs (OR [95% CI]=1.30 [1.17;1.44]), and metastatic cancer (OR
      [95% CI]=1.14 [1.06;1.24]), all P less than 0.01. LIMITATIONS: Impact of Ps
      severity could not be assessed. CONCLUSION: Ps patients had a higher prevalence
      of cancer than Ps-free patients. J Drugs Dermatol. 2018;17(2):180-186.

PMID- 29462227
TI  - Prevalence of Psoriasis in Children and Adolescents in the United States: A
      Claims-Based Analysis.
AB  - IMPORTANCE: While psoriasis (Ps) is mainly characterized as an adult disease, it
      can also develop during childhood. However, prevalence estimates of pediatric
      psoriasis in the United States (US) are lacking. OBJECTIVE: To assess the 2015
      annual prevalence of Ps and moderate-to-severe Ps in pediatric individuals in the
      US. DESIGN: This is a retrospective study based on a large administrative
      insurance claims database in the US. SETTING: Data were extracted from the Truven
      Health Analytics MarketScan(r) Commercial Claims and Encounters database, which
      covers over 60 million individuals with employer-provided health insurance across
      the US. PARTICIPANTS: Over 4.3 million of individuals continuously enrolled in
      their healthcare plan in 2015 and under 18 years of age were included in the
      study. Intervention(s) for Clinical Trials or Exposure(s) for Observational
      Studies: Not applicable. Main Outcome(s) and Measure(s): Ps was defined based on
      medical claims with a diagnosis of Ps (ICD-9-CM: 696.1); moderate-to-severe Ps
      was defined based on medical or pharmacy claims for a systemic treatment
      (biologic, conventional systemic, or phototherapy) for Ps. Overall and age- and
      gender-stratified prevalence was estimated for both Ps and moderate-to-severe Ps.
      RESULTS: The prevalence of Ps was estimated at 128 cases per 100,000 individuals
      (95% CI: 124-131), that of moderate-to-severe Ps at 16 cases per 100,000
      individuals (95% CI: 15-17) in 2015. For both Ps and moderate-to-severe Ps,
      prevalence estimates were numerically higher in females than in males (146 per
      100,000 vs. 110 per 100,000 and 17 per 100,000 vs. 15 per 100,000) and increased
      with age, ranging from 30 per 100,000 in the 0-3 year old group to 205 per
      100,000 in the 12-17 year old group. CONCLUSION AND RELEVANCE: This study
      provides robust estimates of the prevalence of pediatric Ps that can inform
      decisions pertaining to the management of pediatric patients with Ps. J Drugs
      Dermatol. 2018;17(2):187-194.

PMID- 29462228
TI  - Impact of Gene Expression Profiling on Decision-Making in Clinically Node
      Negative Melanoma Patients after Surgical Staging.
AB  - INTRODUCTION: The surgeon's role in the follow-up of pathologic stage I and II
      melanoma patients has traditionally been minimal. Melanoma genetic expression
      profile (GEP) testing provides binary risk assessment (Class 1-low risk, Class 2
      high risk), which can assist in predicting metastasis and formulating appropriate
      follow up. We sought to determine the impact of GEP results on the management of
      clinically node negative cutaneous melanoma patients staged with sentinel lymph
      node biopsy (SLNB). METHODS: A retrospective review of prospectively gathered
      data consisting of patients seen from September 2015 - August 2016 was performed
      to determine whether GEP class influenced follow-up recommendations. Patients
      were stratified into four groups based on recommended follow-up plan: Dermatology
      alone, Surgical Oncology, Surgical Oncology with recommendation for adjuvant
      clinical trial, or Medical and Surgical Oncology. RESULTS: Of ninety-one
      patients, 38 were pathologically stage I, 42 stage II, 10 stage III, and 1 stage
      IV. Combining all stages, GEP Class 1 patients were more likely to be followed by
      Dermatology alone and less like to be followed by Surgical Oncology with
      recommendation for adjuvant trial compared to Class 2 patients (P less than
      0.001). Among stage 1 patients, Class 1 were more likely to follow up with
      Dermatology alone compared to Class 2 patients (82 vs. 0%; P less than 0.001).
      Among stage II patients, GEP Class 1 were more likely to follow up with
      Dermatology alone (21 vs 0%) and more Class 2 patients followed up with surgery
      and recommendations for adjuvant trial (36 vs 64%; P less than 0.05). There was
      no difference in follow up for stage III patients based on the GEP results
      (P=0.76). CONCLUSION: GEP results were significantly associated with the
      management of stage I-II melanoma patients after staging with SLNB. For node
      negative patients, Class 2 results led to more aggressive follow up and
      management. J Drugs Dermatol. 2018;17(2):196-199.

PMID- 29462229
TI  - Safety and Tolerability of Ixekizumab: Integrated Analysis of Injection-Site
      Reactions from 11 Clinical Trials.
AB  - <p>BACKGROUND: Injection-site reactions (ISRs) are reported with biologic
      therapies. The objective of this study was to comprehensively characterize ISRs
      among moderate-to-severe psoriasis patients treated with ixekizumab, a high
      affinity monoclonal antibody that selectively targets interleukin (IL)-17A.</p>
      <p>METHODS: ISRs are presented from UNCOVER-1, UNCOVER-2, and UNCOVER-3 (12
      weeks) and all ixekizumab-exposed patients in 11 controlled and uncontrolled
      trials (156 weeks).</p> <p>RESULTS: At week 12, reported ISR frequency with 80 mg
      ixekizumab every 2 weeks (IXE Q2W, 16.8%) was comparable with etanercept twice
      weekly (16.4%); both were significantly higher than placebo (3.3%). With IXE Q2W,
      ISRs were mild (12.3%), moderate (3.9%), or severe (0.7%), typically reported in
      the first 2 weeks (median onset, 6.6 days), and most commonly characterized as
      nonspecified, erythema, and pain. Generally, erythema onset was delayed, whereas
      pain occurred around drug administration. Discontinuation from ixekizumab due to
      ISRs (0.4%) occurred in the first 12 weeks. After 2 weeks, ISR frequency
      decreased and remained stable (<=4.2%) through week 156. No ISR-related serious
      adverse events were reported in ixekizumab-treated patients. ISR data were
      solicited if patients reported injection-associated events. Since nonspecified
      ISR was the most commonly reported term, specific types might be
      underreported.</p> <p>CONCLUSIONS: ISRs have been reported with ixekizumab during
      clinical trials. These reactions are typically tolerable, manageable, and
      decrease over time.</p> <p>Clinicaltrials.gov: NCT01474512 (UNCOVER-1);
      NCT01597245 (UNCOVER-2); NCT01646177 (UNCOVER-3); NCT01777191 (UNCOVER-A);
      NCT01624233 (UNCOVER-J); NCT01107457 (I1F-MC-RHAJ); NCT02561806 (I1F-MC-RHBS);
      NCT02387801 (I1F-US-RHBO);NCT02513550 (I1F-MC-RHBP); NCT02634801 (I1F-EW
      RHBZ)</p> <p>J Drugs Dermatol. 2018;17(2):200-206.</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- 29462230
TI  - Clinical Pharmacokinetics of Oxymetazoline Cream Following Topical Facial
      Administration for the Treatment of Erythema Associated With Rosacea.
AB  - BACKGROUND: Oxymetazoline cream 1.0% is FDA-approved for the topical treatment of
      persistent facial erythema associated with rosacea in adults. This phase 2,
      multicenter, randomized, double-blind, parallel-group study assessed the
      pharmacokinetics, safety, and tolerability of oxymetazoline in patients with
      moderate to severe erythema associated with rosacea. METHODS: Eligible patients
      were randomized to 1 of 8 treatment groups (oxymetazoline cream 0.5%, 1.0%, or
      1.5% or vehicle applied topically either once or twice daily for 28 days).
      Pharmacokinetic analyses were conducted in patients receiving oxymetazoline.
      Plasma samples for pharmacokinetic assessments were collected prior to dosing and
      6 times postdose on days 1 and 28. RESULTS: A total of 356 patients were included
      in the safety population (oxymetazoline, n=268; vehicle, n=88). Thirty patients
      (11.2%) in the oxymetazoline group reported treatment-related treatment-emergent
      adverse events, most of which were mild to moderate application-site reactions.
      Oxymetazoline, at all concentrations, was generally safe and well tolerated. Mean
      maximum observed plasma concentrations were <=115 pg/mL across all groups; the
      highest mean values for area under the plasma concentration-time curve from time
      0 to 24 hours following once- and twice-daily administration of oxymetazoline
      1.5% were 1680 pg*h/mL and 2660 pg*h/mL, respectively. Systemic exposure to
      oxymetazoline increased dose proportionally with once- and twice-daily
      administration. CONCLUSION: These findings support the use of oxymetazoline for
      the treatment of persistent facial erythema associated with rosacea. J Drugs
      Dermatol. 2018;17(2):213-220.

PMID- 29462231
TI  - Efficacy and Safety of Apremilast in Systemic- and Biologic-Naive Patients With
      Moderate Plaque Psoriasis: 52-Week Results of UNVEIL.
AB  - <p>BACKGROUND: Many patients with moderate plaque psoriasis are undertreated
      despite broadening treatment options. In the phase IV UNVEIL study, oral
      apremilast demonstrated efficacy and safety in systemic-naive patients with
      chronic moderate plaque psoriasis with lower psoriasis-involved body surface area
      (BSA; 5%-10%) during the 16-week, double-blind, placebo-controlled phase. We
      describe efficacy and safety of apremilast in this population through week 52 in
      UNVEIL.</p> <p>METHODS: Patients with moderate plaque psoriasis (BSA 5%-10%;
      static Physician's Global Assessment [sPGA] score of 3 [moderate]) and naive to
      systemic therapies for psoriasis were randomized (2:1) to receive apremilast 30
      mg twice daily or placebo for 16 weeks. At week 16, patients continued on
      apremilast (apremilast/apremilast) or were switched from placebo to apremilast
      (placebo/apremilast) through week 52 (open-label apremilast treatment phase).
      Efficacy assessments included the product of sPGA and BSA (PGAxBSA) (mean
      percentage change from baseline; >=75% reduction from baseline [PGAxBSA-75]),
      sPGA response (achievement of score of 0 [clear] or 1 [almost clear]), and the
      Dermatology Life Quality Index (DLQI; mean change from baseline).</p> <p>RESULTS:
      A total of 136 patients completed the 52-week analysis period
      (placebo/apremilast, n=50/64; apremilast/apremilast, n=86/121). At week 52,
      improvements in all efficacy end points observed at week 16 were maintained in
      the apremilast/apremilast group (mean percentage change from baseline in PGAxBSA:
      -55.5%; PGAxBSA-75: 42.1%; sPGA response: 33.1%; mean change from baseline in
      DLQI score: -4.4); similar improvements emerged in the placebo/apremilast group
      after switching to apremilast. The most common adverse events (>=5% of patients)
      through week 52 were diarrhea (28.0%), nausea (19.0%), headache (15.2%),
      nasopharyngitis (10.4%), upper respiratory tract infection (7.1%), vomiting
      (5.7%), and decreased appetite (5.2%).</p> <p>CONCLUSIONS: Apremilast was
      effective in systemic-naive patients with moderate plaque psoriasis with BSA 5%
      10%; efficacy was sustained through week 52. No new safety signals emerged with
      continued apremilast exposure.</p> <p>ClinicalTrials.gov: NCT02425826</p> <p>J
      Drugs Dermatol. 2018;17(2):221-228.</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> PLEASE CONTACT THE
      PUBLISHER WITH ANY QUESTIONS.

PMID- 29462232
TI  - Treatment of Signs and Symptoms (Pruritus) of Interdigital Tinea Pedis With
      Econazole Nitrate Foam, 1.
AB  - BACKGROUND: Tinea pedis is the most common dermatophyte infection. Treatment is
      critical to alleviate pruritic symptoms, to reduce the risk for secondary
      bacterial infection, and to limit the spread of infection to other body sites or
      other individuals. The objective of this study was to compare the abilities of
      econazole nitrate topical foam, 1% and ketoconazole cream (2%) to reduce
      pruritus, thus improving quality of life, and to determine patient preference for
      the foam product versus the cream product in patients with interdigital tinea
      pedis. STUDY DESIGN: A single-center, investigator-blinded, observational pilot
      study was conducted to compare econazole nitrate topical foam (1%) to
      ketoconazole cream (2%). In this split-body study, 20 subjects received both
      econazole nitrate topical foam and ketoconazole cream and applied the medications
      daily to either the right or left foot for 14 days. Improvements in patient
      quality of life (pruritus) and patient preference were measured using the
      pruritus visual analog scale (VAS), Skindex-16, and patient preference
      questionnaires. RESULTS: Nineteen subjects completed the study and one subject
      was lost to follow-up. Reductions in VAS scores of econazole nitrate topical foam
      were significantly greater than those of ketoconazole cream, indicating the
      superiority of the econazole nitrate foam in reducing pruritus. Skindex-16 data
      showed significant reductions in total scores and individual domains, including
      patient symptom, emotional, and functional domains, by the final visit. Since
      each subject received both medications the questionnaire was not medication
      specific. Responses to patient preference questionnaires showed that econazole
      nitrate topical foam,1% was rated as "good" or "excellent" in all measures
      assessed. One adverse event was noted. CONCLUSION: In patients with interdigital
      tinea pedis, application of econazole nitrate topical foam 1% twice daily for two
      weeks was clinically effective and significantly superior to ketoconazole cream
      2% in reducing pruritus. J Drugs Dermatol. 2018;17(2):229-232.

PMID- 29462233
TI  - Blastomycosis-like Pyoderma Arising in Lichen Planus.
AB  - Blastomycosis-like pyoderma (BLP) is a rare reactive skin disease that is most
      commonly caused by bacterial infection. Herein we present a case of BLP arising
      in lichen planus, a chronic inflammatory disease. We propose Wolf's isotopic
      response, or the appearance of a new skin disease at the site of an existing and
      unrelated disease, as the underlying molecular mechanism responsible for this
      unusual physical presentation. It is important that clinicians recognize atypical
      morphologies such as BLP, which mimics squamous cell carcinoma both clinically
      and pathologically. These similarities highlight the need for a tissue diagnosis
      to identify infectious etiologies and rule out malignancy when BLP is suspected.
      J Drugs Dermatol. 2018;17(2):233-235.

PMID- 29462234
TI  - Correction.
AB  - .

PMID- 29462236
TI  - Sperm-egg interaction and fertilization: past, present, and future.
AB  - Fifty years have passed since the findings of capacitation and acrosome reaction.
      These discoveries and the extensive effort of researchers led to the success of
      in vitro fertilization, which has become a top choice for patients at infertility
      clinics today. The effort to understand the mechanism of fertilization is
      ongoing, but the small number of eggs and similarly small quantity of spermatozoa
      continue to hinder biochemical experiments. The emergence of transgenic animals
      and gene disruption techniques has had a significant effect on fertilization
      research. Factors considered important in the early years were shown not to be
      essential and were replaced by newly found proteins. However, there is much about
      sperm-egg interaction which remains to be learned before we can outline the
      mechanism of fertilization. In fact, our understanding of sperm-egg interaction
      is entering a new stage. Progress in transgenic spermatozoa helped us to observe
      the behavior of spermatozoa in vivo and/or at the moment of sperm-egg fusion.
      These advancements are discussed together with the paradigm-shifting research in
      related fields to help us picture the direction which fertilization research may
      take in the future.

PMID- 29462235
TI  - Quality Improvement After Multiple Fatal Transfusion-Transmitted Bacterial
      Infections.
AB  - Objectives: Transfusion-transmitted bacterial infection (TTBI) from platelet
      components is likely underrecognized and can be fatal. Twenty-four-hour
      prospective culture was felt to be insufficiently preventive after multiple TTBIs
      occurred and strategies to improve safety were sought. Methods: Two fatal and one
      severe TTBIs occurred from a split-apheresis platelet donation contaminated with
      Klebsiella pneumoniae. Improvement opportunities were identified and corrective
      and preventive action (CAPA) followed. Results: To mitigate bacterial
      contamination and improve detection sensitivity, additional prospective culture
      48 hours postcollection was implemented. Since implementation, secondary cultures
      have caught two true positives (0.01%) missed by 24-hour culture. Bacterial
      testing at issue and pathogen reduction were later implemented as an added layer
      of safety. Conclusion: While rare, TTBI is a prominent cause of morbidity and
      mortality from contaminated platelets. The approach to CAPA presented here may
      lower the risk of future transfusion-transmitted infections but must be weighed
      against potential added costs.

PMID- 29462237
TI  - LS-align: an atom-level, flexible ligand structural alignment algorithm for high
      throughput virtual screening.
AB  - Motivation: Sequence-order independent structural comparison, also called
      structural alignment, of small ligand molecules is often needed for computer
      aided virtual drug screening. Although many ligand structure alignment programs
      are proposed, most of them build the alignments based on rigid-body shape
      comparison which cannot provide atom-specific alignment information nor allow
      structural variation; both abilities are critical to efficient high-throughput
      virtual screening. Results: We propose a novel ligand comparison algorithm, LS
      align, to generate fast and accurate atom-level structural alignments of ligand
      molecules, through an iterative heuristic search of the target function that
      combines inter-atom distance with mass and chemical bond comparisons. LS-align
      contains two modules of Rigid-LS-align and Flexi-LS-align, designed for rigid
      body and flexible alignments, respectively, where a ligand-size independent,
      statistics-based scoring function is developed to evaluate the similarity of
      ligand molecules relative to random ligand pairs. Large-scale benchmark tests are
      performed on prioritizing chemical ligands of 102 protein targets involving 1 415
      871 candidate compounds from the DUD-E (Database of Useful Decoys: Enhanced)
      database, where LS-align achieves an average enrichment factor (EF) of 22.0 at
      the 1% cutoff and the AUC score of 0.75, which are significantly higher than
      other state-of-the-art methods. Detailed data analyses show that the advanced
      performance is mainly attributed to the design of the target function that
      combines structural and chemical information to enhance the sensitivity of
      recognizing subtle difference of ligand molecules and the introduces of
      structural flexibility that help capture the conformational changes induced by
      the ligand-receptor binding interactions. These data demonstrate a new avenue to
      improve the virtual screening efficiency through the development of sensitive
      ligand structural alignments. Availability and implementation:
      http://zhanglab.ccmb.med.umich.edu/LS-align/. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29462238
TI  - SecretSanta: flexible pipelines for functional secretome prediction.
AB  - Motivation: The secretome denotes the collection of secreted proteins exported
      outside of the cell. The functional roles of secreted proteins include the
      maintenance and remodelling of the extracellular matrix as well as signalling
      between host and non-host cells. These features make secretomes rich reservoirs
      of biomarkers for disease classification and host-pathogen interaction studies.
      Common biomarkers are extracellular proteins secreted via classical pathways that
      can be predicted from sequence by annotating the presence or absence of N
      terminal signal peptides. Several heterogeneous command line tools and web
      interfaces exist to identify individual motifs, signal sequences and domains that
      are either characteristic or strictly excluded from secreted proteins. However, a
      single flexible secretome-prediction workflow that combines all analytic steps is
      still missing. Results: To bridge this gap the SecretSanta package implements
      wrapper and parser functions around established command line tools for the
      integrative prediction of extracellular proteins that are secreted via classical
      pathways. The modularity of SecretSanta enables users to create tailored
      pipelines and apply them across the whole tree of life to facilitate comparison
      of secretomes across multiple species or under various conditions. Availability
      and implementation: SecretSanta is implemented in the R programming language and
      is released under GPL-3 license. All functions have been optimized and
      parallelized to allow large-scale processing of sequences. The open-source code,
      installation instructions and vignette with use case scenarios can be downloaded
      from https://github.com/gogleva/SecretSanta. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29462239
TI  - Restoration of conformation of mutant p53.

PMID- 29462240
TI  - Reply: Carbohydrate Deficient Transferrin in Patients with Cirrhosis: A Tale of
      Bridges.

PMID- 29462241
TI  - flowLearn: fast and precise identification and quality checking of cell
      populations in flow cytometry.
AB  - Motivation: Identification of cell populations in flow cytometry is a critical
      part of the analysis and lays the groundwork for many applications and research
      discovery. The current paradigm of manual analysis is time consuming and
      subjective. A common goal of users is to replace manual analysis with automated
      methods that replicate their results. Supervised tools provide the best
      performance in such a use case, however they require fine parameterization to
      obtain the best results. Hence, there is a strong need for methods that are fast
      to setup, accurate and interpretable. Results: flowLearn is a semi-supervised
      approach for the quality-checked identification of cell populations. Using a very
      small number of manually gated samples, through density alignments it is able to
      predict gates on other samples with high accuracy and speed. On two state-of-the
      art datasets, our tool achieves median(F1)-measures exceeding 0.99 for 31%, and
      0.90 for 80% of all analyzed populations. Furthermore, users can directly
      interpret and adjust automated gates on new sample files to iteratively improve
      the initial training. Availability and implementation: FlowLearn is available as
      an R package on https://github.com/mlux86/flowLearn. Evaluation data is publicly
      available online. Details can be found in the Supplementary Material.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29462242
TI  - Gonadotropins and their receptors: coevolution, genetic variants, receptor
      imaging, and functional antagonists.
AB  - Gonadotropins belong to the family of dimeric glycoprotein hormones and regulate
      gonadal physiology mediated by G protein-coupled, seven-transmembrane receptors.
      These glycoprotein hormones are widely used in the clinic to promote ovarian
      follicle development and for treating some cases of male infertility. We traced
      the coevolution of dimeric gonadotropin hormones and their receptors, together
      with thyrotropin and its receptor. We updated recent findings on human genetic
      variants of these genes and their association with dizygotic twining, polycystic
      ovarian syndrome, primary ovarian insufficiency, male-limited precocious puberty,
      and infertility. In addition to the known physiological roles of gonadotropin
      receptor signaling in gonadal tissues, we also discussed emerging understanding
      of extragonadal functions of gonadotropins in bones and adipose tissues, together
      with recent advances in in vivo imaging of gonadotropin receptors in live
      animals. Recent development of gonadotropin receptor agonists and antagonists
      were summarized with an emphasis on the development of functional antagonists for
      FSH receptors to alleviate osteoporosis and obesity associated with menopause.

PMID- 29462243
TI  - Combining co-evolution and secondary structure prediction to improve fragment
      library generation.
AB  - Motivation: Recent advances in co-evolution techniques have made possible the
      accurate prediction of protein structures in the absence of a template. Here, we
      provide a general approach that further utilizes co-evolution constraints to
      generate better fragment libraries for fragment-based protein structure
      prediction. Results: We have compared five different fragment library generation
      programmes on three different datasets encompassing over 400 unique protein
      folds. We show that considering the secondary structure of the fragments when
      assembling these libraries provides a critical way to assess their usefulness to
      structure prediction. We then use co-evolution constraints to improve the
      fragment libraries by enriching them with fragments that satisfy constraints and
      discarding those that do not. These improved libraries have better precision and
      lead to consistently better modelling results. Availability and implementation:
      Data is available for download from: http://opig.stats.ox.ac.uk/resources. Flib
      Coevo is available for download from: https://github.com/sauloho/Flib-Coevo.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29462245
TI  - 'Acopia' and 'inability to cope' remain unhelpful and pejorative labels for
      complexity in older adults presenting to the acute hospital.

PMID- 29462244
TI  - Scots pine aminopropyltransferases shed new light on evolution of the polyamine
      biosynthesis pathway in seed plants.
AB  - Background and Aims: Polyamines are small metabolites present in all living cells
      and play fundamental roles in numerous physiological events in plants. The
      aminopropyltransferases (APTs), spermidine synthase (SPDS), spermine synthase
      (SPMS) and thermospermine synthase (ACL5), are essential enzymes in the polyamine
      biosynthesis pathway. In angiosperms, SPMS has evolved from SPDS via gene
      duplication, whereas in gymnosperms APTs are mostly unexplored and no SPMS gene
      has been reported. The present study aimed to investigate the functional
      properties of the SPDS and ACL5 proteins of Scots pine (Pinus sylvestris L.) in
      order to elucidate the role and evolution of APTs in higher plants. Methods:
      Germinating Scots pine seeds and seedlings were analysed for polyamines by high
      performance liquid chromatography (HPLC) and the expression of PsSPDS and PsACL5
      genes by in situ hybridization. Recombinant proteins of PsSPDS and PsACL5 were
      produced and investigated for functional properties. Also gene structures,
      promoter regions and phylogenetic relationships of PsSPDS and PsACL5 genes were
      analysed. Key Results: Scots pine tissues were found to contain spermidine,
      spermine and thermospermine. PsSPDS enzyme catalysed synthesis of both spermidine
      and spermine. PsACL5 was found to produce thermospermine, and PsACL5 gene
      expression was localized in the developing procambium in embryos and tracheary
      elements in seedlings. Conclusions: Contrary to previous views, our results
      demonstrate that SPMS activity is not a novel feature developed solely in the
      angiosperm lineage of seed plants but also exists as a secondary property in the
      Scots pine SPDS enzyme. The discovery of bifunctional SPDS from an evolutionarily
      old conifer reveals the missing link in the evolution of the polyamine
      biosynthesis pathway. The finding emphasizes the importance of pre-existing
      secondary functions in the evolution of new enzyme activities via gene
      duplication. Our results also associate PsACL5 with the development of vascular
      structures in Scots pine.

PMID- 29462246
TI  - Carbohydrate Deficient Transferrin in Patients with Cirrhosis: A Tale of Bridges.

PMID- 29462247
TI  - A new approach for interpreting Random Forest models and its application to the
      biology of ageing.
AB  - Motivation: This work uses the Random Forest (RF) classification algorithm to
      predict if a gene is over-expressed, under-expressed or has no change in
      expression with age in the brain. RFs have high predictive power, and RF models
      can be interpreted using a feature (variable) importance measure. However,
      current feature importance measures evaluate a feature as a whole (all feature
      values). We show that, for a popular type of biological data (Gene Ontology
      based), usually only one value of a feature is particularly important for
      classification and the interpretation of the RF model. Hence, we propose a new
      algorithm for identifying the most important and most informative feature values
      in an RF model. Results: The new feature importance measure identified highly
      relevant Gene Ontology terms for the aforementioned gene classification task,
      producing a feature ranking that is much more informative to biologists than an
      alternative, state-of-the-art feature importance measure. Availability and
      implementation: The dataset and source codes used in this paper are available as
      'Supplementary Material' and the description of the data can be found at:
      https://fabiofabris.github.io/bioinfo2018/web/. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29462248
TI  - Quality-of-life analysis of the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1,
      GCIG study comparing platinum-based versus non-platinum-based chemotherapy in
      patients with partially platinum-sensitive recurrent ovarian cancer.
AB  - Background: MITO-8 showed that prolonging platinum-free interval by introducing
      non-platinum-based chemotherapy (NPBC) does not improve prognosis of patients
      with partially platinum-sensitive recurrent ovarian cancer. Quality of life (QoL)
      was a secondary outcome. Patients and methods: Ovarian cancer patients recurring
      or progressing 6-12 months after previous platinum-based chemotherapy (PBC) were
      randomized to receive PBC or NPBC as first treatment. QoL was assessed at
      baseline, third and sixth cycles, with the EORTC C-30 and OV-28 questionnaires.
      Mean changes and best response were analysed. Progression-free survival, response
      rate, and toxicity are also reported for proper interpretation of data. All
      analyses were based on intention-to-treat. Results: Out of the 215 patients, 151
      (70.2%) completed baseline questionnaire, balanced between the arms; thereafter,
      missing rate was higher in the NPBC arm. At mean change analysis, C30 scores were
      prevalently worse in the NPBC than PBC arm, statistical significance being
      attained for emotional functioning, global health status/QoL, fatigue, and
      dyspnoea (effect sizes ranging from 0.30 to 0.51). Conversely, as for OV28 scale,
      the other chemotherapy side-effects item was significantly worse with PBC at
      three and six cycles, with a larger effect size (0.70 and 0.54, respectively). At
      best response analysis, improvement of emotional functioning and pain and
      worsening of peripheral neuropathy and other chemotherapy side-effects were
      significantly more frequent in the PBC arm. Progression-free survival (median 9
      versus 5 months, P = 0.001) and objective response rate (51.6% versus 19.4%, P =
      0.0001) were significantly better with PBC. Allergy, blood cell count, alopecia,
      nausea, musculoskeletal, and neurological side-effects were more frequent and
      severe with PBC; hand-foot skin reaction, rash/desquamation, mucositis, and
      vascular events were more frequent with NPBC. Conclusion: MITO-8 QoL analysis
      shows that deterioration of some functioning and symptom scales is lower with
      PBC, with improvement of emotional functioning and pain, despite worsening of
      toxicity-related items. ClinicalTrials.gov: NCT00657878.

PMID- 29462249
TI  - Effects of cold treatments on fitness and mode of reproduction in the diploid and
      polyploid alpine plant Ranunculus kuepferi (Ranunculaceae).
AB  - Background and Aims: Alpine plants grow in harsh environments and are thought to
      face occasional frost during the sensitive reproductive phase. Apomixis (asexual
      reproduction via seed) can be advantageous when sexual reproduction is disturbed
      by cold stress. Apomictic polyploids tend to grow in colder climates than their
      sexual diploid relatives. Whether cold temperatures actually induce apomixis was
      unknown to date. Methods: We tested experimentally in climate cabinets for
      effects of low temperatures and repeated frost on phenology, fitness and mode of
      reproduction in diploid and tetraploid cytotypes of the alpine species Ranunculus
      kuepferi. The reproduction mode was determined via flow cytometric seed screening
      (FCSS). Key Results: Diploids produced the first flowers earlier than the
      tetraploids in all treatments. Cold treatments significantly reduced the fitness
      of both cytotypes regarding seed set, and increased the frequency of apomictic
      seed formation in diploids, but not in tetraploids. Over consecutive years, the
      degree of facultative apomixis showed individual phenotypic plasticity.
      Conclusions: Cold stress is correlated to expression of apomixis in warm-adapted,
      diploid R. kuepferi, while temperature-tolerant tetraploids just maintain
      facultative apomixis as a possible adaptation to colder climates. However,
      expression of apomixis may not depend on polyploidy, but rather on failure of the
      sexual pathway.

PMID- 29462250
TI  - The lncLocator: a subcellular localization predictor for long non-coding RNAs
      based on a stacked ensemble classifier.
AB  - Motivation: The long non-coding RNA (lncRNA) studies have been hot topics in the
      field of RNA biology. Recent studies have shown that their subcellular
      localizations carry important information for understanding their complex
      biological functions. Considering the costly and time-consuming experiments for
      identifying subcellular localization of lncRNAs, computational methods are
      urgently desired. However, to the best of our knowledge, there are no
      computational tools for predicting the lncRNA subcellular locations to date.
      Results: In this study, we report an ensemble classifier-based predictor,
      lncLocator, for predicting the lncRNA subcellular localizations. To fully exploit
      lncRNA sequence information, we adopt both k-mer features and high-level
      abstraction features generated by unsupervised deep models, and construct four
      classifiers by feeding these two types of features to support vector machine
      (SVM) and random forest (RF), respectively. Then we use a stacked ensemble
      strategy to combine the four classifiers and get the final prediction results.
      The current lncLocator can predict five subcellular localizations of lncRNAs,
      including cytoplasm, nucleus, cytosol, ribosome and exosome, and yield an overall
      accuracy of 0.59 on the constructed benchmark dataset. Availability and
      implementation: The lncLocator is available at
      www.csbio.sjtu.edu.cn/bioinf/lncLocator. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 29462251
TI  - Histoplasma Urinary Antigen Testing Obviates the Need for Coincident Serum
      Antigen Testing.
AB  - Objectives: Serum and urine antigen (SAg, UAg) detection are common tests for
      Histoplasma capsulatum. UAg detection is more widely used and reportedly has a
      higher sensitivity. We investigated whether SAg detection contributes
      meaningfully to the initial evaluation of patients with suspected histoplasmosis.
      Methods: We reviewed 20,285 UAg and 1,426 SAg tests ordered from 1997 to 2016 and
      analyzed paired UAg and SAg tests completed on the same patient within 1 week. We
      determined the positivity rate for each test. Results: Of 601 paired specimens,
      542 were concurrent negatives and 48 were concurrent positives (98% agreement).
      Medical records were available for eight of 11 pairs with discrepant results. UAg
      was falsely positive in six instances, truly positive once, and falsely negative
      once. Conclusions: These findings support using a single antigen detection test,
      rather than both UAg and SAg, as an initial screen for suspected histoplasmosis.
      This aligns with the current practice of most physicians.

PMID- 29462252
TI  - Toward optimizing outcomes in Her2-positive gastric cancer: timing and genomic
      context matter.

PMID- 29462253
TI  - Overview of current systemic management of EGFR-mutant NSCLC.
AB  - Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)
      therapy is the standard of care for lung cancer patients with sensitising EGFR
      mutations (exon 19 deletion or L858R mutation). Several phase III studies have
      demonstrated the superiority of gefitinib, erlotinib (first generation of TKIs)
      or afatinib (second generation) to chemotherapy in progression-free survival and
      response rates. Drug-related toxicities, such as diarrhoea, acneiform skin rash,
      mucositis, and paronychia, are frequently encountered in patients who receive
      EGFR TKIs. Other rare side-effects, such as hepatic impairment and interstitial
      lung disease, should be identified early and managed carefully. Patients with
      uncommon EGFR mutations, such as G719X, S768I, and L861Q, may require special
      selection of EGFR TKIs. The combination of erlotinib plus bevacizumab has been
      accepted in certain parts of the world as an alternative front-line treatment.
      This review article summarizes the studies leading to the establishment of EGFR
      TKIs in EGFR-mutant lung cancer patients. The side-effect profiles of the current
      EGFR TKIs in these large trials are listed, and the management of uncommon EGFR
      mutations is discussed. Finally, the potential role of combination front-line
      treatment is discussed.

PMID- 29462254
TI  - Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine
      kinase inhibitors.
AB  - Patients with non-small-cell lung cancer (NSCLC) whose tumours harbour activating
      mutations within the epidermal growth factor receptor (EGFR) frequently derive
      significant clinical and radiographic benefits from treatment with EGFR tyrosine
      kinase inhibitors (TKIs). As such, prospective identification of EGFR mutations
      is now the standard of care worldwide. However, acquired therapeutic resistance
      to these agents invariably develops. Over the past 10 years, great strides have
      been made in defining the molecular mechanisms of EGFR TKI resistance in an
      effort to design rational strategies to overcome this acquired drug resistance.
      Approximately 60% of patients with acquired resistance to the EGFR TKIs
      (erlotinib, gefitinib, and afatinib) develop a new mutation within the drug
      target. This mutation-T790M-has been shown to alter drug binding and enzymatic
      activity of the mutant EGF receptor. Less common mechanisms of acquired
      resistance include MET amplification, ERBB2 amplification, transformation to
      small-cell lung cancer, and others. Here, we present a condensed overview of the
      literature on EGFR-mutant NSCLC, paying particular attention to mechanisms of
      drug resistance, recent clinical trial results, and novel strategies for
      identifying and confronting drug resistance, while also striving to identify gaps
      in current knowledge. These advances are rapidly altering the treatment landscape
      for EGFR-mutant NSCLC, expanding the armamentarium of available therapies to
      maximize patient benefit.

PMID- 29462255
TI  - Osimertinib and other third-generation EGFR TKI in EGFR-mutant NSCLC patients.
AB  - Osimertinib was the first third-generation epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitor (TKI) to receive FDA and EMA approval for
      metastatic EGFR-mutant non-small-cell lung cancer (NSCLC) patients that have
      acquired the EGFR T790M resistance mutation. Clinical trials have demonstrated
      the efficacy of osimertinib in this patient population and clinical trials of
      other third-generation EGFR TKI are currently under way. Additional challenges in
      this patient population, such as the upfront efficacy of osimertinib, validation
      of T790M in liquid biopsies as a dynamic predictive marker of efficacy, along
      with combination with immune checkpoint inhibitors are being explored,
      representing an extraordinary time of development for EGFR-mutant NSCLC.

PMID- 29462256
TI  - Molecular mechanisms of acquired resistance to third-generation EGFR-TKIs in EGFR
      T790M-mutant lung cancer.
AB  - Lung cancer represents the leading cause of cancer-related deaths worldwide.
      Despite great advances in its management with the recent emergence of molecular
      targeted therapies for non-small-cell lung cancer (NSCLC), relapse of the
      metastatic disease always occurs within approximately one year. Epidermal growth
      factor receptor (EGFR) mutant tumours are the prime example of oncogene addiction
      and clonal evolution in oncology, regarding the emergence of resistance to first-
      and second-generation EGFR inhibitors. Multiple studies have revealed that the
      EGFR-T790M gatekeeper mutation is the main cause of tumour escape. Recently,
      irreversible pyrimidine-based EGFR inhibitors especially designed for this
      particular setting have shown robust clinical activity. However, similar to first
      and second-generation inhibitors, the development of a diversified set of
      resistance mechanisms in response to these new compounds is an emerging issue. To
      date, clinical management of this growing number of patients has not been clearly
      established, even if anecdotal responses to subsequent molecularly guided
      therapies have been observed. By exhaustively reviewing and classifying all the
      preclinical and clinical data published on resistance to third-generation EGFR
      inhibitors in NSCLC, this work reveals the heterogeneity of the mechanisms that a
      tumour can develop to evade therapeutic pressure. Strategies currently being
      tested in clinical trials are discussed in light of these findings.

PMID- 29462257
TI  - Are liquid biopsies a surrogate for tissue EGFR testing?
AB  - Molecular profiling has changed the treatment landscape in advanced non-small
      cell lung cancer. Accurately identifying the tumours that harbour sensitizing
      EGFR mutations, the most common targetable molecular alteration, as well as those
      with acquired resistance mutations (e.g. T790M) on treatment is a high clinical
      priority. The current clinical gold standard is genotyping of tumour specimens.
      However, the practical utility of this approach is limited by the lack of
      available tissue and the potential complications associated with biopsies. With
      the advent of newer sequencing assays, it has become feasible to assess tumour
      genomics via a blood sample, termed a 'liquid biopsy'. In this review, we
      summarize the available techniques for liquid biopsies and their applicability
      for detecting sensitizing and resistance EGFR mutations and how these results may
      be used for making treatment decisions.

PMID- 29462258
TI  - Tyrosine kinase inhibition of EGFR: a successful history of targeted therapy for
      NSCLC since 20 years.

PMID- 29462260
TI  - Introducing whole-genome sequencing into routine cancer care: the Genomics
      England 100 000 Genomes Project.

PMID- 29462261
TI  - The TGFbeta superfamily in cardiac dysfunction.
AB  - TGFbeta superfamily includes the transforming growth factor betas (TGFbetas),
      bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs) and
      Activin/Inhibin families of ligands. Among the 33 members of TGFbeta superfamily
      ligands, many act on multiple types of cells within the heart, including
      cardiomyocytes, cardiac fibroblasts/myofibroblasts, coronary endothelial cells,
      smooth muscle cells, and immune cells (e.g. monocytes/macrophages and
      neutrophils). In this review, we highlight recent discoveries on TGFbetas, BMPs,
      and GDFs in different cardiac residential cellular components, in association
      with functional impacts in heart development, injury repair, and dysfunction.
      Specifically, we will review the roles of TGFbetas, BMPs, and GDFs in cardiac
      hypertrophy, fibrosis, contractility, metabolism, angiogenesis, and regeneration.

PMID- 29462262
TI  - 50 years of spermatogenesis: Sertoli cells and their interactions with germ
      cells.
AB  - The complex morphology of the Sertoli cells and their interactions with germ
      cells has been a focus of investigators since they were first described by Enrico
      Sertoli. In the past 50 years, information on Sertoli cells has transcended
      morphology alone to become increasingly more focused on molecular questions. The
      goal of investigators has been to understand the role of the Sertoli cells in
      spermatogenesis and to apply that information to problems relating to male
      fertility. Sertoli cells are unique in that they are a nondividing cell
      population that is active for the reproductive lifetime of the animal and
      cyclically change morphology and gene expression. The numerous and distinctive
      junctional complexes and membrane specializations made by Sertoli cells provide a
      scaffold and environment for germ cell development. The increased focus of
      investigators on the molecular components and putative functions of testicular
      cells has resulted primarily from procedures that isolate specific cell types
      from the testicular milieu. Products of Sertoli cells that influence germ cell
      development and vice versa have been characterized from cultured cells and from
      the application of transgenic technologies. Germ cell transplantation has shown
      that the Sertoli cells respond to cues from germ cells with regard to
      developmental timing and has furthered a focus on spermatogenic stem cells and
      the stem cell niche. Very basic and universal features of spermatogenesis such as
      the cycle of the seminiferous epithelium and the spermatogenic wave are initiated
      by Sertoli cells and maintained by Sertoli-germ cell cooperation.

PMID- 29462259
TI  - The oocyte-to-embryo transition in mouse: past, present, and future.
AB  - The oocyte-to-embryo transition (OET) arguably initiates with formation of a
      primordial follicle and culminates with reprogramming of gene expression during
      the course of zygotic genome activation. This transition results in converting a
      highly differentiated cell, i.e. oocyte, to undifferentiated cells, i.e. initial
      blastomeres of a preimplantation embryo. A plethora of changes occur during the
      OET and include, but are not limited to, changes in transcription, chromatin
      structure, and protein synthesis; accumulation of macromolecules and organelles
      that will comprise the oocyte's maternal contribution to the early embryo;
      sequential acquisition of meiotic and developmental competence to name but a few.
      This review will focus on transcriptional and post-transcriptional changes that
      occur during OET in mouse because such changes are likely the major driving force
      for OET. We often take a historical and personal perspective, and highlight how
      advances in experimental methods often catalyzed conceptual advances in
      understanding the molecular bases for OET. We also point out questions that
      remain open and therefore represent topics of interest for future investigation.

PMID- 29462263
TI  - Regular Yogurt Intake and Risk of Cardiovascular Disease Among Hypertensive
      Adults.
AB  - BACKGROUND: High blood pressure (HBP) is a major cardiovascular disease (CVD)
      risk factor. Clinical trials including Dietary Approaches to Stop Hypertension
      (DASH) have demonstrated beneficial effects of dairy consumption on risks of HBP
      and CVD. Yogurt, a fermented dairy product, may independently be related to CVD
      risk. OBJECTIVE: To evaluate the association between yogurt consumption and CVD
      risk among hypertensive individuals in 2 large cohorts and to determine whether
      the association differs among those whose eating pattern more closely resembles
      the DASH diet. METHODS: Overall, 55,898 female Nurses' Health Study (NHS) and
      18,232 male Health Professionals Follow-Up Study (HPFS) participants with
      prevalent HBP were included. Cumulative average estimates of yogurt intake from
      validated food frequency questionnaires were related to verified self-reported
      CVD outcomes using Cox proportional hazards models. Hazard ratios and 95%
      confidence intervals (CI) were adjusted for CVD risk factors, medications, and
      diet covariates. RESULTS: Yogurt intake was inversely associated with CVD risk
      (myocardial infarction and stroke) among hypertensive participants (P <0.01 in
      both cohorts). Among participants consuming >=2 servings/week of yogurt, NHS
      women had a 17% (95% CI: 0.74-0.92) lower risk while HPFS men experienced a 21%
      (95% CI: 0.66-0.96) lower CVD risk compared to those who consumed <1
      serving/month. Regular yogurt consumers with higher DASH diet scores had 16% (95%
      CI: 0.73-0.96) and 30% (95% CI: 0.57-0.85) CVD risk reductions in the 2 cohorts,
      respectively. CONCLUSION: Hypertensive men and women who consumed >=2
      servings/week of yogurt, especially in the context of a healthy diet, were at
      lower risk for developing CVD.

PMID- 29462264
TI  - The Effect of Ambient Humidity on the Metabolic Rate and Respiratory Patterns of
      the Hissing Cockroach, Gromphadorhina portentosa (Blattodea: Blaberidae).
AB  - We examined the effects of humidity on the metabolic rates and respiratory
      patterns of Gromphadorhina portentosa (Schaum) (Blattodea: Blaberidae) to
      determine whether insects transition from continuous, cyclical, and discontinuous
      (DGC) respiration in response to water conservation. Eight male G. portentosa
      were placed under five different humidity treatments (0, 23, 40, 60, 80% RH).
      Using flow through respirometry we: (i) determined the effect of humidity on
      metabolic rate; (ii) observed if changes in metabolic rate were correlated with
      changes in closed/flutter (CF) or the open (O) phase of DGC; and (iii) determined
      whether increased spiracular closure was correlated with an increase in water
      retention. Although G. portentosa had similar rates of CO2 release when placed
      under 0, 40, 60, and 80% RH, cockroaches placed at 23% RH had a significantly
      higher metabolic rate. There was no effect of humidity on the duration of the CF
      phase of the DGC. However, the O phase of DGC was significantly longer when G.
      portentosa was placed at humidity levels above 23% RH. Interestingly, we saw that
      the average rate of mass lost to the environment did not change when cockroaches
      were placed at humidity levels ranging from 0 to 80% RH. This suggests that
      modulation of the spiracles allows G. portentosa to regulate the amount of water
      lost to the environment.

PMID- 29462265
TI  - High Baseline CD4 Counts and Antiretroviral Therapy Cessation.

PMID- 29462266
TI  - Effects of Rifampin and Doxycycline Treatments in Patients With Uncomplicated
      Scrub Typhus: An Open-Label, Randomized, Controlled Trial.
AB  - Background: Doxycycline is currently the most frequently used treatment in
      patients with scrub typhus. However, doxycycline-resistant strains have been
      found, necessitating the development of a new treatment. Rifampin is known to be
      effective even for such strains. Our aim in this study was to compare the effects
      of rifampin and doxycycline treatment in patients with scrub typhus in areas in
      which resistance to doxycycline has not been reported. Methods: Patients admitted
      to Chosun University Hospital and regional network hospitals between 2007 and
      2009 with a body temperature >=37.5 degrees C and suspected to have scrub typhus
      were randomly assigned to 1 of 2 treatment groups: a group administered
      doxycycline 100 mg twice daily for 5 days and a group administered rifampin 600
      mg once daily for 5 days. For treatment outcomes, fever, headache, muscle ache,
      and rash clearance times were compared between the groups. Results: The rifampin
      and doxycycline groups showed equivalence in all treatment outcomes evaluated.
      The proportions of patients with fever clearance within 48 hours were similar
      between groups. Furthermore, there was no significant difference in the
      occurrence of side effects following drug administration between groups.
      Conclusions: On the basis of the finding that equivalent treatment effects and
      safety were found in patient groups that received 600 mg of rifampin and 200 mg
      of doxycycline, respectively, for 5 days to treat scrub typhus, rifampin may be
      considered an alternative treatment to doxycycline. Clinical Trials Registration:
      NCT00568711.

PMID- 29462267
TI  - Reply to Pan et al.

PMID- 29462268
TI  - In situ tissue regeneration using a warp-knitted fabric in the canine aorta and
      inferior vena cava.
AB  - OBJECTIVES: Materials used in paediatric cardiac surgery have drawbacks of
      deterioration, calcification and pseudointimal proliferation resulting in
      haemodynamic disturbance. The aim of this study was to investigate whether these
      drawbacks can be overcome by in situ tissue regeneration using a newly developed
      synthetic hybrid fabric (SHF). METHODS: The SHF is an expandable, warp-knitted
      fabric composed of a combination of biodegradable [poly-l-lactic acid (PLLA)] and
      non-biodegradable (polyethylene terephthalate) yarns. The fabric is coated with
      cross-linked gelatin. Mechanical properties of the SHF were compared with those
      of 2 commercial products: expanded polytetrafluoroethylene sheet and
      glutaraldehyde-treated bovine pericardium. An oval-shaped defect created in the
      canine descending aorta or inferior vena cava was filled with the SHF patch.
      After 2 weeks and 1, 3, 6 and 12 (or 24 in the inferior vena cava) months, the
      patch was removed for histological examination and evaluation of the remaining
      PLLA. RESULTS: The SHF exhibited satisfactory tensile and suture retention
      strength for surgical implantation similar to or better than the 2 commercial
      products. Tissue regeneration was induced with multilayered smooth muscle cells
      and collagen fibres on both sides of the patch, along with a mature endothelial
      layer and tissue connections containing vasa vasorum across the patch in the
      aorta and inferior vena cava. Inflammatory reactions were minimal, and no calcium
      deposition occurred. The molecular weight of PLLA was reduced to half at 12
      months after implantation. CONCLUSIONS: The SHF may solve the drawbacks of the
      existing products. Further studies of the expandability of the SHF patch after
      degradation of PLLA are warranted.

PMID- 29462269
TI  - Smoking Cessation and 16-year Trajectories of Functional Limitations Among Dutch
      Older Adults: Results from the Longitudinal Aging Study Amsterdam.
AB  - Background: This study examined whether smoking cessation in middle age and old
      age is associated with following a successful trajectory of functional
      limitations over time in Dutch older adults. Methods: We used 16-year
      longitudinal data from 645 participants of the Longitudinal Aging Study
      Amsterdam. Three types of trajectories regarding functional limitations over time
      were defined: successful (high initial level of functioning and limited decline),
      late decline (high initial level of functioning and late onset of decline), and
      early decline (lower initial level of functioning and early onset of decline).
      Smoking cessation status was self-reported and categorized into: early quitters
      (stopped in middle age [35-40 years]), late quitters (already smoked in middle
      age and stopped in old age [>=55 years]), and continued smokers (smoked in middle
      age and still smoking in old age). Multinomial Logistic Regression Analyses were
      used to assess the association between smoking cessation and trajectory
      membership. Results: The sample (55-85 years at baseline) consisted of 20.3%
      early quitters, 22.9% late quitters, and 56.8% continued smokers. After
      adjustment for confounders, the model showed that late quitters were less likely
      to follow an early decline trajectory instead of a successful trajectory compared
      to continued smokers (odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.24
      0.97). After adjustment for clinically relevant level of depressive symptoms,
      this association remained substantial but was no longer statistically significant
      (OR = 0.50, 95% CI = 0.24-1.02). Conclusions: Although not statistically
      significant in the full model, the observed associations suggest that smoking
      cessation in old age may have an important impact on daily functioning in old
      age.

PMID- 29462270
TI  - Reply to Arnold and Beavin.

PMID- 29462272
TI  - Reasons for conversion and adverse intraoperative events in Endoscopic Port
      AccessTM atrioventricular valve surgery and minimally invasive aortic valve
      surgery.
AB  - OBJECTIVES: This study reports the factors that contribute to sternotomy
      conversions (SCs) and adverse intraoperative events in minimally invasive aortic
      valve surgery (MI-AVS) and minimally invasive Endoscopic Port AccessTM
      atrioventricular valve surgery (MI-PAS). METHODS: In total, 3780 consecutive
      patients with either aortic valve disease or atrioventricular valve disease
      underwent minimally invasive valve surgery (MIVS) at our institution between 1
      February 1997 and 31 March 2016. MI-AVS was performed in 908 patients (mean age
      69.2 +/- 11.3 years, 45.2% women, 6.2% redo cardiac surgery) and MI-PAS in 2872
      patients (mean age 64.1 +/- 13.3 years, 46.7% women, 12.2% redo cardiac surgery).
      RESULTS: A cumulative total of 4415 MIVS procedures (MI-AVS = 908, MI-PAS = 3507)
      included 1537 valve replacements (MI-AVS = 896, MI-PAS = 641) and 2878 isolated
      or combined valve repairs (MI-AVS = 12, MI-PAS = 2866). SC was required in 3.0%
      (n = 114 of 3780) of MIVS patients, which occurred in 3.1% (n = 28 of 908) of MI
      AVS patients and 3.0% (n = 86 of 2872) of MI-PAS patients, respectively. Reasons
      for SC in MI-AVS included inadequate visualization (n = 4, 0.4%) and arterial
      cannulation difficulty (n = 7, 0.8%). For MI-PAS, SC was required in 54 (2.5%)
      isolated mitral valve procedures (n = 2183). Factors that contributed to SC in MI
      PAS included lung adhesions (n = 35, 1.2%), inadequate visualization (n = 2,
      0.1%), ventricular bleeding (n = 3, 0.1%) and atrioventricular dehiscence (n = 5,
      0.2%). Neurological deficit occurred in 1 (0.1%) and 3 (3.5%) MI-AVS and MI-PAS
      conversions, respectively. No operative or 30-day mortalities were observed in MI
      AVS conversions (n = 28). The 30-day mortality associated with SC in MI-PAS (n =
      86) was 10.5% (n = 9). CONCLUSIONS: MIVS is increasingly being recognized as the
      'gold-standard' for surgical valve interventions in the context of rapidly
      expanding catheter-based technology and increasing patient expectations. Surgeons
      need to be aware of factors that contribute to SC and adverse intraoperative
      outcomes to ensure that patients enjoy the maximum potential benefit of MIVS and
      to apply effective risk reduction strategies that encourage safer and sustainable
      MIVS programmes.

PMID- 29462273
TI  - Pneumocystis Is Still Involved in Nonimmunosuppressed Preterm Infants in Europe.

PMID- 29462274
TI  - Increased Methicillin-Resistant Staphylococcus aureus Septicemia and Illicit
      Intravenous Drug Use in the South.

PMID- 29462271
TI  - Emerging therapeutic potential of graviola and its constituents in cancers.
AB  - Cancer remains a leading cause of death in the USA and around the world. Although
      the current synthetic inhibitors used in targeted therapies have improved patient
      prognosis, toxicity and development of resistance to these agents remain a
      challenge. Plant-derived natural products and their derivatives have historically
      been used to treat various diseases, including cancer. Several leading
      chemotherapeutic agents are directly or indirectly based on botanical natural
      products. Beyond these important drugs, however, a number of crude herbal or
      botanical preparations have also shown promising utility for cancer and other
      disorders. One such natural resource is derived from certain plants of the family
      Annonaceae, which are widely distributed in tropical and subtropical regions.
      Among the best known of these is Annona muricata, also known as soursop, graviola
      or guanabana. Extracts from the fruit, bark, seeds, roots and leaves of graviola,
      along with several other Annonaceous species, have been extensively investigated
      for anticancer, anti-inflammatory and antioxidant properties. Phytochemical
      studies have identified the acetogenins, a class of bioactive polyketide-derived
      constituents, from the extracts of Annonaceous species, and dozens of these
      compounds are present in different parts of graviola. This review summarizes
      current literature on the therapeutic potential and molecular mechanism of these
      constituents from A.muricata against cancer and many non-malignant diseases.
      Based on available data, there is good evidence that these long-used plants could
      have both chemopreventive and therapeutic potential. Appropriate attention to
      safety studies will be important to assess their effectiveness on various
      diseases caused or promoted by inflammation.

PMID- 29462275
TI  - Excitation of Cortical nNOS/NK1R Neurons by Hypocretin 1 is Independent of Sleep
      Homeostasis.
AB  - We have proposed that cortical nNOS/NK1R interneurons have a role in sleep
      homeostasis. The hypocretins (orexins) are wake-promoting neuropeptides and
      hypocretin/orexin (Hcrt) neurons project to the cortex. Hcrt peptides affect deep
      layer cortical neurons, and Hcrt receptor 1 (Hcrtr1; Ox1r) mRNA is expressed in
      cortical nNOS/NK1R cells. Therefore, we investigated whether Hcrt neuron
      stimulation affects cingulate cortex nNOS/NK1R neurons. Bath application of
      HCRT1/orexin-A evoked an inward current and membrane depolarization in most
      nNOS/NK1R cells which persisted in tetrodotoxin; optogenetic stimulation of Hcrt
      terminals expressing channelrhodopsin-2 confirmed these results, and
      pharmacological studies determined that HCRTR1 mediated these responses. Single
      cell RT-PCR found Hcrtr1 mRNA in 31% of nNOS/NK1R cells without any Hcrtr2 mRNA
      expression; immunohistochemical studies of Hcrtr1-EGFP mice confirmed that a
      minority of nNOS/NK1R cells express HCRTR1. When Hcrt neurons degenerated in
      orexin-tTA;TetO DTA mice, the increased EEG delta power during NREM sleep
      produced in response to 4 h sleep deprivation and c-FOS expression in cortical
      nNOS/NK1R cells during recovery sleep were indistinguishable from that of
      controls. We conclude that Hcrt excitatory input to these deep layer cells is
      mediated through HCRTR1 but is unlikely to be involved in the putative role of
      cortical nNOS/NK1R neurons in sleep homeostasis.

PMID- 29462276
TI  - Influence of Rearing Substrates and Nontarget Hosts on the Bionomics of the
      Tachinid Parasitoid Nemorilla maculosa (Diptera: Tachinidae).
AB  - The tachinid Nemorilla maculosa Meigen (Diptera: Tachinidae) was introduced from
      Taiwan to Benin for evaluating its potential as a biocontrol candidate against
      the cowpea pest Maruca vitrata (Fabricius) (Lepidoptera: Crambidae). To optimize
      its rearing, we assessed the influence of M. vitrata larval age and rearing
      substrate-cowpea germinating grains and peabush leaves-on its life table
      parameters, while its host specificity was investigated with regard to nontarget
      effects. Parasitism rates were higher when older larvae (10- and 14-d old) were
      offered to females of N. maculosa compared to the younger (2-, 4-, and 6-d old)
      host larvae. Regardless of the rearing substrate, development time was longer for
      females than males, and females lived longer than males irrespective of the age
      of the host. Sex ratio did not vary significantly with host ages or rearing
      substrate. The average number of eggs laid by a female reared from M. vitrata
      larvae feeding on cowpea germinating grains or peabush leaves was 94.2 +/- 4.38
      and 71.9 +/- 1.70 eggs, respectively. The host suitability of N. maculosa was
      assessed by testing four nontarget Lepidoptera species: Spodoptera littoralis
      Boisduval (Lepidoptera: Noctuidae), Sesamia calamistis Hampson (Lepidoptera:
      Noctuidae), Corcyra cephalonica (Stainton) (Lepidoptera: Pyralidae), and Eldana
      saccharina Walker (Lepidoptera: Pyralidae). Larvae of S. littoralis and C.
      cephalonica were successfully parasitized while N. maculosa did not develop in
      the larvae of E. saccharina and S. calamistis although they were parasitized.
      Despite the potential of N. maculosa as a biological control agent against the
      pod borer M. vitrata, more detailed nontarget studies, extending to other native
      Crambidae species, are needed before making decisions on field releases.

PMID- 29462277
TI  - The value of oligoclonal bands in the multiple sclerosis diagnostic criteria.
AB  - The presence of oligoclonal bands in clinically isolated syndromes is an
      independent risk factor for developing multiple sclerosis and has been largely
      excluded from the more recent multiple sclerosis diagnostic criteria. Therefore,
      our objective was to explore the value of oligoclonal bands in the context of the
      2010 McDonald criteria, especially in patients fulfilling exclusively
      dissemination in space at baseline. For this purpose, we selected 566 patients
      from a clinically isolated syndrome inception cohort who had IgG oligoclonal
      bands determination and sufficient data on baseline brain MRI to assess
      dissemination in space and time. We excluded the cases already fulfilling both
      dissemination in space and time and divided the remaining 398 into 'no
      dissemination in space and time' (n = 218), 'dissemination in space' (n = 164)
      and 'dissemination in time' (n = 16). We assessed Cox proportional hazards
      regression models with 2010 McDonald as the outcome, using 'no dissemination in
      space and time' with 0 lesions and negative oligoclonal bands as the reference
      for different subgroups according to oligoclonal bands status
      (positive/negative). To assess the diagnostic properties, we selected cases with
      a follow-up >=3 years or fulfilling 2010 McDonald within 3 years of the
      clinically isolated syndrome (n = 314), and compared the performance of all
      'dissemination in space' cases (n = 137) versus patients with 'dissemination in
      space' and positive oligoclonal bands (n = 101). The remaining patients
      classified as fulfilling 'dissemination in time' or 'no dissemination in space
      and time' were taken into account to calculate the diagnostic properties. The
      respective adjusted hazard ratios (95% confidence interval) were 1.5 (0.4-5.7)
      for 'no dissemination in space and time' with 0 lesions and positive oligoclonal
      bands, 3.1 (1.4-7.2) for 'no dissemination in space and time' with >=1 lesions
      and negative oligoclonal bands, 7.4 (3.5-15.7) for 'no dissemination in space and
      time' with >=1 lesions and positive oligoclonal bands, 10.4 (4.8-22.6) for
      'dissemination in space' with negative oligoclonal bands, 15.3 (7.5-31.3) for
      'dissemination in space' with positive oligoclonal bands, and 9.1 (3.5-23.4) for
      'dissemination in time' (not subdivided due to the sample size). The specificity
      for all cases with 'dissemination in space' was 80.6 and increased to 88.1 after
      selecting those with positive oligoclonal bands. According to these results, we
      propose radiological dissemination in space at any time plus positive oligoclonal
      bands as an additional criterion for diagnosing multiple sclerosis.

PMID- 29462278
TI  - Neonatal Ethanol Disturbs the Normal Maturation of Parvalbumin Interneurons
      Surrounded by Subsets of Perineuronal Nets in the Cerebral Cortex: Partial
      Reversal by Lithium.
AB  - Reduction in parvalbumin-positive (PV+) interneurons is observed in adult mice
      exposed to ethanol at postnatal day 7 (P7), a late gestation fetal alcohol
      spectrum disorder model. To evaluate whether PV+ cells are lost, or PV expression
      is reduced, we quantified PV+ and associated perineuronal net (PNN)+ cell
      densities in barrel cortex. While PNN+ cell density was not reduced by P7
      ethanol, PV cell density decreased by 25% at P90 with no decrease at P14. PNN+
      cells in controls were virtually all PV+, whereas more than 20% lacked PV in
      ethanol-treated adult animals. P7 ethanol caused immediate apoptosis in 10% of
      GFP+ cells in G42 mice, which express GFP in a subset of PV+ cells, and GFP+ cell
      density decreased by 60% at P90 without reduction at P14. The ethanol effect on
      PV+ cell density was attenuated by lithium treatment at P7 or at P14-28. Thus,
      reduced PV+ cell density may be caused by disrupted cell maturation, in addition
      to acute apoptosis. This effect may be regionally specific: in the dentate gyrus,
      P7 ethanol reduced PV+ cell density by 70% at P14 and both PV+ and PNN+ cell
      densities by 50% at P90, and delayed lithium did not alleviate ethanol's effect.

PMID- 29462279
TI  - Mechanisms for the establishment and maintenance of pregnancy: synergies from
      scientific collaborations.
AB  - Research on the functions of interferon tau (IFNT) led to the theory of pregnancy
      recognition signaling in ruminant species. But IFNT does much more as it induces
      expression of interferon regulatory factor 2 (IRF2) in uterine luminal (LE),
      superficial glandular (sGE), but not glandular (GE) epithelia. First, IRF2
      silences transcription of the estrogen receptor alpha gene and, indirectly,
      transcription of the oxytocin receptor gene to abrogate development of the
      luteolytic mechanism to prevent regression of the corpus luteum and its
      production of progesterone for establishing and maintaining pregnancy. Second,
      IRF2 silences expression of classical interferon-stimulated genes in uterine LE
      and sGE; however, uterine LE and sGE respond to progesterone (P4) and IFNT to
      increase expression of genes for transport of nutrients into the uterine lumen
      such as amino acids and glucose. Other genes expressed by uterine LE and sGE
      encode for adhesion molecules such as galectin 15, cathepsins, and cystatins for
      tissue remodeling, and hypoxia-inducible factor relevant to angiogenesis and
      survival of blastocysts in a hypoxic environment. IFNT is also key to a
      servomechanism that allows uterine epithelia, particularly GE, to proliferate and
      to express genes in response to placental lactogen and placental growth hormone
      in sheep. The roles of secreted phosphoprotein 1 are also discussed regarding its
      role in implantation in sheep and pigs, as well as its stimulation of expression
      of mechanistic target of rapamycin mRNA and protein which is central to
      proliferation, migration, and gene expression in the trophectoderm cells.

PMID- 29462282
TI  - Pathophysiological understanding of HFpEF: microRNAs as part of the puzzle.
AB  - Half of all heart failure patients have preserved ejection fraction (HFpEF).
      Comorbidities associated with and contributing to HFpEF include obesity, diabetes
      and hypertension. Still, the underlying pathophysiological mechanisms of HFpEF
      are unknown. A preliminary consensus proposes that the multi-morbidity triggers a
      state of systemic, chronic low-grade inflammation, and microvascular dysfunction,
      causing reduced nitric oxide bioavailability to adjacent cardiomyocytes. As a
      result, the cardiomyocyte remodels its contractile elements and fails to relax
      properly, causing diastolic dysfunction, and eventually HFpEF. HFpEF is a complex
      syndrome for which currently no efficient therapies exist. This is notably due to
      the current one-size-fits-all therapy approach that ignores individual patient
      differences. MicroRNAs have been studied in relation to pathophysiological
      mechanisms and comorbidities underlying and contributing to HFpEF. As regulators
      of gene expression, microRNAs may contribute to the pathophysiology of HFpEF. In
      addition, secreted circulating microRNAs are potential biomarkers and as such,
      they could help stratify the HFpEF population and open new ways for
      individualized therapies. In this review, we provide an overview of the ever
      expanding world of non-coding RNAs and their contribution to the molecular
      mechanisms underlying HFpEF. We propose prospects for microRNAs in stratifying
      the HFpEF population. MicroRNAs add a new level of complexity to the regulatory
      network controlling cardiac function and hence the understanding of gene
      regulation becomes a fundamental piece in solving the HFpEF puzzle.

PMID- 29462283
TI  - Erratum: Methods for handling longitudinal outcome processes truncated by dropout
      and death.

PMID- 29462281
TI  - Linking hospital patient records for suspected or established acute coronary
      syndrome in a complex secondary care system: a proof-of-concept e-registry in
      National Health Service Scotland.
AB  - Aims: To implement secondary care electronic record linkage for patients
      hospitalized with suspected or known acute coronary syndrome (ACS) in a complex
      regional health care system and evaluate this e-Registry in terms of patterns of
      service delivery and 1-year outcomes. Methods and results: Existing electronic
      hospital records were linked to create episodes of care using (i) a patient
      administration system, (ii) invasive cardiovascular procedure referrals, and
      (iii) a catheter laboratory record. Data were extracted for admissions (1 October
      2013-30 September 2014) with International Classification of Disease (ICD)-10
      diagnosis of angina (I200-I209), myocardial infarction (I210-I229), other
      ischaemic heart disease (I240-I249) or heart failure (I50), linked to other
      sources to develop a secondary care ACS e-registry and analysed within a Safe
      Haven. Episodes of care were categorized into care pathways and evaluated in
      terms of patient characteristics, as well as service delivery metrics and
      outcomes including mortality. In all, 2327 patients had 2472 episodes of care.
      Diagnoses were hierarchically classified as ST-elevation myocardial infarction
      (STEMI) (586, 25.2%), non-ST-elevation myocardial infarction (NSTEMI) (1068,
      45.9%), unspecified myocardial infarction (146, 6.3%), unstable angina (527,
      22.6%) for the first hospitalization for each patient within the study period.
      Six care pathways were mapped. Percutaneous coronary intervention rate for STEMI
      was 80.2% and for NSTEMI 33.1%. Unadjusted all-cause mortality was 9.0% and 3.0%
      for STEMI and NSTEMI at 30 days, rising to 11.9% and 11.6% at 1 year. Analyses
      were validated by independent source data verification. Conclusion: The e
      registry has enabled analysis of ACS hospitalizations in a complex health care
      system with implications for quality improvement and research.

PMID- 29462284
TI  - A matter of thrombosis: different thrombus-like formations in balloon-expandable
      transcatheter aortic valve prostheses.
AB  - OBJECTIVES: Transcatheter aortic valve implantation is a treatment strategy for
      degenerated aortic valve prostheses, but there is some concern regarding valve
      thrombosis. The optimal anticoagulation strategy for implantation of a
      transcatheter aortic valve prosthesis remains unclear. METHODS: Aortic root
      models with the Sapien-XT and S3 prostheses (sizes 23 and 26) fixed in a
      Perimount Magna Ease bioprosthesis (sizes 23 and 25) were constructed. The
      haemodynamics of the left ventricle were imitated in a proved in vitro model.
      Milk was used for coagulation after 90s. Different areas of the leaflets (W: wall
      coagulation, C: commissure coagulation left/right and S: sinus coagulation) were
      examined and the number of thrombus-like formations was counted. RESULTS: A total
      of 54% of the thrombus-like formations were found in the sinus, 28% at the wall
      area, 13% at the right commissure and 10% at the left commissure. Significant
      differences were detected at the wall area. S3 prostheses had significantly more
      thrombus-like formations than the XT prostheses. Additionally, in the S3
      prostheses, the thrombus-like formation resembled a film whereas in the XT
      prostheses, the thrombus-like formation was like the crumbs of a cake. We noted
      exactly the same pattern in explanted prostheses from patients. CONCLUSIONS: The
      Sapien prostheses tend to form thromboses due to their flow properties. More than
      half of the thrombus-like formations were seen in the sinus. The S3 prostheses
      had significantly more thrombus-like formations than the XT prostheses in the
      wall area. There are different patterns of thrombus-like formations in XT and S3
      prostheses used for transcatheter aortic valve implantation both in vivo and in
      vitro.

PMID- 29462285
TI  - Association of 10-year C-reactive protein trajectories with markers of healthy
      aging: findings from the English Longitudinal Study of Ageing.
AB  - Background: Elevated systematic inflammation is a hallmark of aging, but the
      association of long-term inflammation trajectories with subsequent aging
      phenotypes has been little examined. We assessed inflammatory marker C-reactive
      protein (CRP) repeatedly over time and examined whether long-term changes
      predicted aging outcomes. Methods: A total of 2,437 men and women aged 47-87
      years at baseline (1998-2001) who were participants in the English Longitudinal
      Study of Ageing had CRP measured on two or three occasions between 1998 and 2009.
      Inflammation trajectories were computed using latent-class growth mixture
      modelling and were related to aging outcomes measured in 2012/2013: physical
      functioning, cardiometabolic, respiratory, mental health, and a composite
      "healthy aging" outcome. Results: Four CRP trajectories were identified: 'stable
      low' (71% of the sample) with baseline mean 1.33mg/L remaining <3mg/L; 'medium-to
      high' (14%) with baseline 2.7mg/L rising to 5.3mg/L; 'high-to-medium' (10%) with
      baseline 6.6mg/L decreasing to 2.4mg/L; 'stable-high' (5%) with levels from 5.7
      to 7.5mg/L. Relative to the stable-low trajectory, individuals in the medium-to
      high had a higher risk of limitations in basic activities of daily living (ADL,
      Odds Ratio; 95% Confidence Interval: 2.09; 1.51,2.88), instrumental ADL (1.62;
      1.15,2.30), impaired balance (1.59; 1.20,2.11) and walking speed (1.61;
      1.15,2.24), arthritis (1.55; 1.16,2.06), hypertension (1.57; 1.21,2.04), obesity
      (1.95; 1.36,2.80), poor respiratory function (1.84; 1.36,2.50), and depression
      (1.55; 1.13,2.12). A lower odds of healthy aging was observed in people in the
      medium-to-high (0.57; 0.40,0.79) and stable-high (0.50; 0.27,0.91) trajectories.
      Conclusions: Older people who displayed an elevation in CRP levels over a decade
      experienced an increased risk of adverse aging outcomes.

PMID- 29462286
TI  - The c-index is not proper for the evaluation of $t$-year predicted risks.
AB  - We show that the widely used concordance index for time to event outcome is not
      proper when interest is in predicting a $t$-year risk of an event, for example 10
      year mortality. In the situation with a fixed prediction horizon, the concordance
      index can be higher for a misspecified model than for a correctly specified
      model. Impropriety happens because the concordance index assesses the order of
      the event times and not the order of the event status at the prediction horizon.
      The time-dependent area under the receiver operating characteristic curve does
      not have this problem and is proper in this context.

PMID- 29462287
TI  - Cytoskeletal Associated Filamin A and RhoA Affect Neural Progenitor Specification
      During Mitosis.
AB  - Neural progenitor proliferation and cell fate decision from self-renewal to
      differentiation are crucial factors in determining brain size and morphology. The
      cytoskeletal dependent regulation of these processes is not entirely known. The
      actin-binding filamin A (FlnA) was shown to regulate proliferation of progenitors
      by directing changes in cell cycles proteins such as Cdk1 during G2/M phase. Here
      we report that functional loss of FlnA not only affects the rate of proliferation
      by altering cell cycle length but also causes a defect in early differentiation
      through changes in cell fate specification. FlnA interacts with Rho GTPase RhoA,
      and FlnA loss impairs RhoA activation. Disruption of either of these cytoskeletal
      associated proteins delays neurogenesis and promotes neural progenitors to remain
      in proliferative states. Aurora kinase B (Aurkb) has been implicated in
      cytokinesis, and peaks in expression during the G2/M phase. Inhibition of FlnA or
      RhoA impairs Aurkb degradation and alters its localization during mitosis.
      Overexpression of Aurkb replicates the same delay in neurogenesis seen with loss
      of FlnA or RhoA. Our findings suggest that shared cytoskeletal processes can
      direct neural progenitor proliferation by regulating the expression and
      localization of proteins that are implicated in the cell cycle progression and
      cell fate specification.

PMID- 29462288
TI  - Sperm acrosome reaction: its site and role in fertilization.
AB  - Manner and roles of sperm acrosome reaction in a variety of animals were
      compared.

PMID- 29462289
TI  - Medial Thigh Lift for Patients Following Massive Weight Loss: Our Postbariatric
      Experience.

PMID- 29462280
TI  - Clinical Practice Guidelines for Clostridium difficile Infection in Adults and
      Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and
      Society for Healthcare Epidemiology of America (SHEA).
AB  - A panel of experts was convened by the Infectious Diseases Society of America
      (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the
      2010 clinical practice guideline on Clostridium difficile infection (CDI) in
      adults. The update, which has incorporated recommendations for children
      (following the adult recommendations for epidemiology, diagnosis, and treatment),
      includes significant changes in the management of this infection and reflects the
      evolving controversy over best methods for diagnosis. Clostridium difficile
      remains the most important cause of healthcare-associated diarrhea and has become
      the most commonly identified cause of healthcare-associated infection in adults
      in the United States. Moreover, C. difficile has established itself as an
      important community pathogen. Although the prevalence of the epidemic and
      virulent ribotype 027 strain has declined markedly along with overall CDI rates
      in parts of Europe, it remains one of the most commonly identified strains in the
      United States where it causes a sizable minority of CDIs, especially healthcare
      associated CDIs. This guideline updates recommendations regarding epidemiology,
      diagnosis, treatment, infection prevention, and environmental management.

PMID- 29462290
TI  - Commentary on: Breast Erythema in a Patient With Breast Implant-Associated
      Anaplastic Large Cell Lymphoma: A Case Report Discussing Cutaneous
      Manifestations.

PMID- 29462291
TI  - Risk Factors for Recurrent Helicobacter cinaedi Bacteremia and the Efficacy of
      Selective Digestive Decontamination With Kanamycin to Prevent Recurrence.
AB  - Background: Previous studies suggest that Helicobacter cinaedi can cause
      recurrent bacteremia. In this study, we elucidated the risk factors for recurrent
      H. cinaedi bacteremia and explored the efficacy of selective digestive
      decontamination (SDD) as a preventive measure. Methods: We retrospectively
      reviewed the medical records of patients with H. cinaedi bacteremia between March
      2009 and December 2016 at 2 Japanese hospitals. Results: We identified 168
      patients with H. cinaedi bacteremia. Bacteremia recurred in 34 patients. The 100
      day cumulative incidence rate of recurrent bacteremia was 18.7%. In univariate
      analysis of factors associated with recurrent bacteremia, anticancer chemotherapy
      (hazard ratio [HR], 3.75; 95% confidence interval [CI], 1.86-7.58; P < .001),
      systemic steroids (HR, 3.79; 95% CI, 1.70-8.45; P = .0011), and hematological
      malignancy (HR, 3.18; 95% CI, 1.64-6.19; P < .001) were detected. Multivariate
      analysis indicated that anticancer chemotherapy (HR, 2.47; 95% CI, 1.19-5.12; P =
      .015) and systemic steroids (HR, 2.40; 95% CI, 1.03-5.61; P = .044) were the
      independent risk factors. Of the 168 patients, 47 received SDD. According to
      Gray's test, SDD might have reduced the rate of recurrence but this was not
      statistically significant (HR, 0.46; 95% CI, 0.18-1.18; P = .11). However, in a
      proportional hazard modeling analysis, SDD reduced the rate of recurrence (HR,
      0.36; 95% CI, 0.13-1.00; P = .050). Conclusions: The 100-day cumulative incidence
      of recurrent H. cinaedi bacteremia was 18.7%. Anticancer chemotherapy and
      systemic steroids were independent risk factors for recurrent bacteremia. SDD is
      a potential strategy for reducing the recurrence.

PMID- 29462292
TI  - State and non-state mental health service collaboration in a South African
      district: a mixed methods study.
AB  - The Life Esidimeni tragedy in South Africa showed that, despite significant
      global gains in recognizing the salience of integrated public mental health care
      during the past decade, crucial gaps remain. State and non-state mental health
      service collaboration is a recognized strategy to increase access to care and
      optimal use of community resources, but little evidence exist about how it
      unfolds in low- to middle-income countries. South Africa's Mental Health Policy
      Framework and Strategic Plan 2013-20 (MHPF) underlines the importance of
      collaborative public mental health care, though it is unclear how and to what
      extent this happens. The aim of the study was to explore the extent and nature of
      state and non-state mental health service collaboration in the Mangaung
      Metropolitan District, Free State, South Africa. The research involved an equal
      status, sequential mixed methods design, comprised of social network analysis
      (SNA) and semi-structured interviews. SNA-structured interviews were conducted
      with collaborating state and non-state mental health service providers. Semi
      structured interviews were conducted with collaborating partners and key stake
      holders. Descriptive network analyses of the SNA data were performed with Gephi,
      and thematic analysis of the semi-structured interview data were performed in
      NVivo. SNA results suggested a fragmented, hospital centric network, with low
      average density and clustering, and high authority and influence of a specialist
      psychiatric hospital. Several different types of collaborative interactions
      emerged, of which housing and treatment adherence a key point of collaboration.
      Proportional interactions between state and non-state services were low.
      Qualitative data expanded on these findings, highlighting the range of available
      mental health services, and pointed to power dynamics as an important
      consideration in the mental health service network. The fostering of a well
      integrated system of care as proposed in the MHPF requires inter-institutional
      arrangements that include both clinical and social facets of care, and
      improvements in local governance.

PMID- 29462294
TI  - Triple hybrid imaging of a high-risk coronary plaque: morphology, perfusion, and
      haemorheology.

PMID- 29462293
TI  - Intrathecal gene therapy in mouse models expressing CMT1X mutations.
AB  - Gap junction beta-1 (GJB1) gene mutations affecting the gap junction protein
      connexin32 (Cx32) cause the X-linked Charcot-Marie-Tooth disease (CMT1X), a
      common inherited neuropathy. Targeted expression of virally delivered Cx32 in
      Schwann cells following intrathecal injection of lentiviral vectors in the Cx32
      knockout (KO) mouse model of the disease has led to morphological and functional
      improvement. To examine whether this approach could be effective in CMT1X
      patients expressing different Cx32 mutants, we treated transgenic Cx32 KO mice
      expressing the T55I, R75W or N175D CMT1X mutations. All three mutants were
      localized in the perinuclear compartment of myelinating Schwann cells consistent
      with retention in the ER (T55I) or Golgi (R75W, N175D) and loss of physiological
      expression in the non-compact myelin. Following intrathecal delivery of the GJB1
      gene we detected the virally delivered wild-type (WT) Cx32 in non-compact myelin
      of T55I KO mice, but only rarely in N175D KO or R75W KO mice, suggesting dominant
      negative effects of the R75W and N175D mutants but not of the T55I mutant on co
      expressed WT Cx32. GJB1 treated T55I KO mice showed improved motor performance,
      lower ratios of abnormally myelinated fibers and reduction of inflammatory cells
      in spinal roots and peripheral nerves compared with mock-treated littermates.
      Either partial (N175D KO) or no (R75W KO) improvement was observed in the other
      two mutant lines. Thus, certain CMT1X mutants may interfere with gene addition
      therapy for CMT1X. Whereas gene addition can be used for non-interfering CMT1X
      mutations, further studies will be needed to develop treatments for patients
      harboring interfering mutations.

PMID- 29462295
TI  - An expanded enzyme toolbox for production of cis, cis-muconic acid and other
      shikimate pathway derivatives in Saccharomyces cerevisiae.
AB  - A wide range of commercially relevant aromatic chemicals can be synthesized via
      the shikimic acid pathway. Thus, this pathway has been the target of diverse
      metabolic engineering strategies. In the present work, an optimized yeast strain
      for production of the shikimic acid pathway intermediate 3-dehydroshikimate (3
      DHS) was generated, which is a precursor for the production of the valuable
      compounds cis, cis-muconic acid (CCM) and gallic acid (GA). Production of CCM
      requires the overexpression of the heterologous enzymes 3-DHS dehydratase AroZ,
      protocatechuic acid (PCA) decarboxylase AroY and catechol dioxygenase CatA. The
      activity of AroY limits the yield of the pathway. This repertoire of enzymes was
      expanded by a novel fungal decarboxylase. Introducing this enzyme into the
      pathway in the optimized strain, a titer of 1244 mg L-1 CCM could be achieved,
      yielding 31 mg g-1 glucose. This represents the highest yield of this compound
      reported in Saccharomyces cerevisiae to date. To demonstrate the applicability of
      the optimized strain for production of other compounds from 3-DHS, we
      overexpressed AroZ together with a mutant of a para-hydroxybenzoic acid
      hydroxylase with improved substrate specificity for PCA, PobAY385F. Thereby, we
      could demonstrate the production of GA for the first time in S. cerevisiae.

PMID- 29462296
TI  - Public health monitoring of hypertension, diabetes and elevated cholesterol:
      comparison of different data sources.
AB  - Background: Three data sources are generally used in monitoring health on the
      population level. Health interview surveys (HISs) are based on participants' self
      report. Health examination surveys (HESs) yield more objective data, and also
      persons who are unaware of their elevated risks can be detected. Medical records
      (MRs) and other administrative registers also provide objective data, but their
      availability, coverage and quality vary between countries. We summarized studies
      comparing self-reported data with (i) measured data from HESs or (ii) MRs. We
      aimed to describe differences in feasibility and comparability of different data
      sources for monitoring (i) elevated blood pressure or hypertension (ii) elevated
      blood glucose or diabetes and (iii) elevated total cholesterol. Methods: We
      conducted a literature search to identify studies, which validated self-reported
      measures against objective measures. We found 30 studies published since the year
      2000 fulfilling our inclusion criteria (targeted to adults and comparing
      prevalence among the same persons). Results: Hypertension and elevated total
      cholesterol were prone to be under-estimated in HISs. The under-estimate was more
      pronounced, when the HIS data were compared with HES data, and lower when
      compared with MRs. For diabetes, the HISs and the objective methods resulted in
      fairly similar prevalence rates. Conclusion: The three data sources measure
      different manifestations of the risk factors and cannot be expected to yield
      similar prevalence rates. Using HIS data only may lead to under-estimation of
      elevated risk factor levels or disease prevalence. Whenever possible, information
      from the three data sources should be evaluated and combined.

PMID- 29462297
TI  - Patients' knowledge and attitudes regarding living with implantable electronic
      devices: results of a multicentre, multinational patient survey conducted by the
      European Heart Rhythm Association.

PMID- 29462299
TI  - Purification and molecular characterization of a Metschnikowia saccharicola
      killer toxin lethal to a crab pathogenic yeast.
AB  - The marine yeast strain Metschnikowia saccharicola DD21-2, isolated from
      sediments in the Yalu River, produces a killer toxin with a lethal effect on
      Metschnikowia bicuspidate strain WCY, a pathogenic yeast strain that infects
      crabs. In this study, the killer toxin was purified and characterized. After
      sequential purification, the purity of the killer toxin was increased 72.2-fold
      over the purity of the yeast cell culture supernatant. The molecular weight of
      the purified killer toxin was 47.0 kDa. The optimal pH and temperature for
      killing activity were 5.5 degrees C and 16 degrees C, respectively. The killing
      activity was stable over a pH range of 4.0-6.5 and temperature range of 0 degrees
      C-40 degrees C. The purified killer toxin was only effective against toxin
      sensitive integral cells and had no killing effect on the protoplasts of toxin
      sensitive cells. When exerting the killing effect, the toxin bind to a cell wall
      receptor of the treated strain, disrupted cell wall integrity and eventually
      caused death. The amino acid sequence identified by mass spectroscopy indicated
      that the purified killer toxin might be a protein kinase, but did not show beta
      1,3-glucanase activity, consistent with the laminarin hydrolysis results. These
      findings provide a basis for disease prevention and control in marine
      aquaculture.

PMID- 29462298
TI  - Th17 cells differentiated with mycelial membranes of Candida albicans prevent
      oral candidiasis.
AB  - Candida albicans is a human commensal that causes opportunistic infections. Th17
      cells provide resistance against mucosal infection with C. albicans; however, the
      T cell antigens remain little known. Our final goal is to find effective T cell
      antigens of C. albicans that are responsible for immunotherapy against
      candidiasis. Here, we prepared fractions including cytosol, membrane and cell
      wall from yeast and mycelial cells. Proteins derived from a membrane fraction of
      mycelial cells effectively induced differentiation of CD4+ T cells into IL-17A
      producing Th17 cells. To confirm the immunological response in vivo of proteins
      from mycelial membrane, we performed adoptive transfer experiments using ex vivo
      stimulated CD4+ T cells from IL-17A-GFP reporter mice. Mycelial membrane
      differentiated CD4+ Th17 cells adoptively transferred intravenously prevented
      oral candidiasis by oral infection of C. albicans, compared with control anti-CD3
      stimulated CD4+ T cells. This was confirmed by the clinical score and the number
      of neutrophils on the infected tissues. These data suggest that effective T cell
      antigens against candidiasis could be present in the membrane protein fraction of
      mycelial cells. The design of novel vaccination strategies against candidiasis
      will be our next step.

PMID- 29462300
TI  - DNA stable-isotope probing identifies uncultivated members of Pseudonocardia
      associated with biodegradation of pyrene in agricultural soil.
AB  - Identifying functional microorganisms involved in the degradation of high
      molecular-mass polycyclic aromatic hydrocarbons (HMM-PAHs) in agricultural soil
      environments could assist in developing bioremediation strategies for soil PAH
      contamination. Active populations of HMM-PAH degraders in agricultural soils are
      currently poorly understood. In this study, we identified aerobic pyrene
      degrading bacteria in agricultural and industrial soils by [13C]pyrene
      incubations followed by DNA stable-isotope probing and high-throughput
      sequencing. More than 80% of pyrene was degraded during an incubation time of 35
      days in both soils, with slower mineralization rates observed in agricultural
      soil compared with industrial soil. Members of the Pseudonocardia genus, not
      previously implicated in pyrene degradation, were the dominant pyrene-degrading
      population in agricultural soil; their relative abundance increased by three
      orders of magnitude. In industrial soil, Arthrobacter sp. appeared as the major
      pyrene degraders, while Pseudonocardia was not detectable. Mycobacterium, a group
      of well-known pyrene degraders, was found to be active in pyrene degradation in
      both soils. These results highlight the role of uncultivated members of
      Pseudonocardia in natural PAH biodegradation processes and expand our
      understanding of the metabolic potential of uncultivated microorganisms for
      bioremediation applications in agricultural soils.

PMID- 29462301
TI  - Secreted bacterial RNA: an unexplored avenue.
AB  - Gradually, it is becoming clear that our well-being depends significantly on the
      contribution and composition of microorganisms that are associated with us. The
      majority of human-associated microorganisms are bacteria, which maintain their
      niche through interactions with the human host and neighboring microorganisms.
      Secretory products contribute largely to maintaining their position in a complex
      ecosystem. The role of bacterial-released secreted RNA (seRNA) is mostly
      unexplored, and the study on seRNA will open a new branch in science. There are
      observations that have demonstrated the functional potential of seRNA, but more
      investigations are required to cover the entire path from their origin to
      function.

PMID- 29462302
TI  - Isolation of marine xylene-utilizing bacteria and characterization of
      Halioxenophilus aromaticivorans gen. nov., sp. nov. and its xylene degradation
      gene cluster.
AB  - Seven xylene-utilizing bacterial strains were isolated from seawater collected
      off the coast of Japan. Analysis of 16S rRNA gene sequences indicated that six
      isolates were most closely related to the marine bacterial genera Alteromonas,
      Marinobacter or Aestuariibacter. The sequence of the remaining strain, KU68FT,
      showed low similarity to the 16S rRNA gene sequences of known bacteria with
      validly published names, the most similar species being Maricurvus
      nonylphenolicus strain KU41ET (92.6% identity). On the basis of physiological,
      chemotaxonomic and phylogenetic data, strain KU68FT is suggested to represent a
      novel species of a new genus in the family Cellvibrionaceae of the order
      Cellvibrionales within the Gammaproteobacteria, for which the name
      Halioxenophilus aromaticivorans gen. nov., sp. nov. is proposed. The type strain
      of Halioxenophilus aromaticivorans is KU68FT (=JCM 19134T = KCTC 32387T). PCR and
      sequence analysis revealed that strain KU68FT possesses an entire set of genes
      encoding the enzymes for the upper xylene methyl-monooxygenase pathway, xylCMABN,
      resembling the gene set of the terrestrial Pseudomonas putida strain mt-2.

PMID- 29462304
TI  - Erratum.

PMID- 29462305
TI  - Health insurance and care-seeking behaviours of female migrants in Accra, Ghana.
AB  - People working in Ghana's informal sector have low rates of enrolment in the
      publicly funded National Health Insurance Scheme. Informal sector workers,
      including migrant girls and women from northern Ghana working as head porters
      (kayayei), report challenges obtaining insurance and seeking formal health care.
      This article analyses how health insurance status affects kayayei migrants' care
      seeking behaviours. This mixed-methods study involved surveying 625 migrants
      using respondent-driven sampling and conducting in-depth interviews with a sub
      sample of 48 migrants. Analyses explore health status and health seeking
      behaviours for recent illness/injury. Binary logistic regression modelled the
      effects of selected independent variables on whether or not a recently
      ill/injured participant (n = 239) sought health care. Although recently
      ill/injured participants (38.4%) desired health care, less than half (43.5%)
      sought care. Financial barriers overwhelmingly limit kayayei migrants from
      seeking health care, preventing them from registering with the National Health
      Insurance Scheme, renewing their expired health insurance policies, or taking
      time away from work. Both insured and uninsured migrants did not seek formal
      health services due to the unpredictable nature of out-of-pocket expenses.
      Catastrophic and impoverishing medical expenses also drove participants'
      migration in search of work to repay loans and hospital bills. Health insurance
      can help minimize these expenditures, but only 17.4% of currently insured
      participants (58.2%) reported holding a valid health insurance card in Accra. The
      others lost their cards or forgot them when migrating. Access to formal health
      care in Accra remains largely inaccessible to kayayei migrants who suffer from
      greater illness/injury than the general female population in Accra and who are
      hindered in their ability to receive insurance exemptions. With internal
      migration on the rise in many settings, health systems must recognize the varied
      needs of populations in multi-ethnic and multilingual countries to ensure that
      internal migrants can access affordable, quality health services across domestic
      borders.

PMID- 29462303
TI  - SNAIL Mediates TGF-beta1-Induced Downregulation of Pentraxin 3 Expression in
      Human Granulosa Cells.
AB  - Transforming growth factor-beta (TGF-beta) 1 plays a critical role in regulating
      follicular development, and its dysregulation has been shown to be involved in
      the pathogenesis of ovulation dysfunction. SNAIL is a well-known transcriptional
      repressor that mediates TGF-beta1-induced cellular functions. Pentraxin 3 (PTX3)
      is a key enzyme for the assembly and stabilization of the cumulus oophorus
      extracellular matrix, which is essential for cumulus expansion during the
      periovulatory stage. The purpose of the present study was to investigate the
      roles of TGF-beta1 and SNAIL in the regulation of PTX3 expression and to examine
      the underlying mechanism. An established immortalized human granulosa cell (GC)
      line (SVOG), a GC tumor cell line (KGN), and primary human granulosa-lutein cells
      were used as study models. We demonstrated that TGF-beta1 treatment substantially
      decreased the messenger RNA and protein levels of PTX3. This suppressive effect
      was abolished by cotreatment with the soluble TGF-beta type II receptor
      (TbetaRII) or the ALK4/5/7 inhibitor SB431542. Knockdown of ALK5, SMAD2/3, or
      SMAD4 reversed the effects of TGF-beta1-induced SNAIL upregulation and PTX3
      suppression. These results indicate that TGF-beta1 upregulates SNAIL and
      downregulates PTX3 expression via a TbetaRII-ALK5-mediated SMAD-dependent
      signaling pathway in human GCs. Additionally, TGF-beta1-induced PTX3 suppression
      was mediated by upregulation of the SNAIL transcription factor, as knockdown of
      SNAIL completely reversed the suppression of PTX3 in response to TGF-beta1. These
      findings could inform the roles of TGF-beta1 and SNAIL in the regulation of
      follicular function and might provide therapeutic targets for the treatment of
      ovulation dysfunction.

PMID- 29462306
TI  - A multicentre stewardship initiative to decrease excessive duration of antibiotic
      therapy for the treatment of community-acquired pneumonia.
AB  - Background: The increased emphasis on pneumonia-related performance measures and
      patient outcomes has led hospitals to implement multifaceted approaches to
      quickly identify patients with community-acquired pneumonia (CAP), start timely
      therapy and reduce readmission. However, there has been minimal focus on duration
      of therapy (DOT) and patients often receive prolonged antibiotic courses. The
      IDSA and American Thoracic Society (IDSA/ATS) CAP guidelines recommend 5 days of
      therapy for clinically stable patients that quickly defervesce and stewardship
      teams are well positioned to influence prescribing practices. Objectives:
      Determine the impact of a prospective stewardship intervention on total
      antibiotic DOT and associated clinical outcomes in hospitalized patients with
      CAP. Methods: This multicentre, quasi-experimental study evaluated three
      concurrent interventions over a 6 month period to promote appropriate DOT. All
      centres updated institutional CAP guidelines to promote IDSA/ATS-concordant DOT,
      provided education and conducted daily audit and feedback with intervention to
      provide patient-specific DOT recommendations. Results: A total of 600 patients
      with CAP were included (307 in the historical control group and 293 in the
      stewardship intervention group). The stewardship intervention increased
      compliance with DOT recommendations (42% versus 5.6%, P < 0.001) and reduced the
      median DOT per patient (6 versus 9 days, P < 0.001). Clinical outcomes, including
      mortality, readmission with pneumonia, presentation to the emergency
      centre/clinic with pneumonia and incidence of Clostridium difficile infection
      within 30 days of discharge, were not different between groups. Conclusions: This
      multicentre evaluation of a stewardship intervention in hospitalized CAP patients
      reduced the total antibiotic DOT and increased guideline-concordant DOT without
      adversely affecting patient outcomes.

PMID- 29462307
TI  - 'Artlift' arts-on-referral intervention in UK primary care: updated findings from
      an ongoing observational study.
AB  - Background: Arts for health interventions are an accepted option for medical
      management of mental wellbeing in health care. Updated findings are presented
      from a prospective longitudinal follow-up (observational) design study of an arts
      on referral programme in UK general practice, over a 7-year period (2009-2016).
      Methods: Primary care process and mental wellbeing outcomes were investigated,
      including progress through the intervention, changes in mental wellbeing, and
      factors associated with those outcomes. A total of n =1297 patients were referred
      to an eight or 10-week intervention over a period from 2009 to 2016. Patient
      sociodemographic information was recorded at baseline, and patient progress (e.g.
      attendance) assessed throughout the intervention. Results: Of all referrals,
      51.7% completed their course of prescribed art (the intervention). Of those that
      attended, 74.7% engaged with the intervention as rated by the artists leading the
      courses. A significant increase in wellbeing was observed from pre- to post
      intervention (t = -19.29, df =523, P < 0.001, two-tailed) for those that
      completed and/or engaged. A sub sample (N =103) of these referrals self-reported
      multi-morbidities. These multiple health care service users were majority
      completers (79.6%), and were rated as having engaged (81.0%). This group also had
      a significant increase in well-being, although this was smaller than for the
      group as a whole (t = -7.38, df =68, P < 0.001). Conclusion: Findings confirm
      that art interventions can be effective in the promotion of well-being for those
      that complete, including those referred with multi-morbidity, with significant
      changes in wellbeing evident across the intervention periods.

PMID- 29462308
TI  - Comment on: Influence of empirical double-active combination antimicrobial
      therapy compared with active monotherapy on mortality in patients with septic
      shock: a propensity score-adjusted and matched analysis.

PMID- 29462309
TI  - Fixation of CO2 and CO on a diverse range of carbohydrates using anaerobic, non
      photosynthetic mixotrophy.
AB  - Biological CO2 fixation is an important technology that can assist in combating
      climate change. Here, we show an approach called anaerobic, non-photosynthetic
      mixotrophy can result in net CO2 fixation when using a reduced feedstock. This
      approach uses microbes called acetogens that are capable of concurrent
      utilization of both organic and inorganic substrates. In this study, we
      investigated the substrate utilization of 17 different acetogens, both mesophilic
      and thermophilic, on a variety of different carbohydrates and gases. Compared to
      most model acetogen strains, several non-model mesophilic strains displayed
      greater substrate flexibility, including the ability to utilize disaccharides,
      glycerol and an oligosaccharide, and growth rates. Three of these non-model
      strains (Blautia producta, Clostridium scatologenes and Thermoanaerobacter kivui)
      were chosen for further characterization, under a variety of conditions including
      H2- or syngas-fed sugar fermentations and a CO2-fed glycerol fermentation. In all
      cases, CO2 was fixed and carbon yields approached 100%. Finally, the model
      acetogen C. ljungdahlii was engineered to utilize glucose, a non-preferred sugar,
      while maintaining mixotrophic behavior. This work demonstrates the flexibility
      and robustness of anaerobic, non-photosynthetic mixotrophy as a technology to
      help reduce CO2 emissions.

PMID- 29462310
TI  - Bulk soil and maize rhizosphere resistance genes, mobile genetic elements and
      microbial communities are differently impacted by organic and inorganic
      fertilization.
AB  - Organic soil fertilizers, such as livestock manure and biogas digestate,
      frequently contain bacteria carrying resistance genes (RGs) to antimicrobial
      substances and mobile genetic elements (MGEs). The effects of different
      fertilizers (inorganic, manure, digestate) on RG and MGE abundance and microbial
      community composition were investigated in a field plot experiment. The relative
      abundances of RGs [sul1, sul2, tet(A), tet(M), tet(Q), tet(W), qacEDelta1/qacE]
      and MGEs [intI1, intI2, IncP-1, IncP-1epsilon and LowGC plasmids] in total
      community (TC)-DNA from organic fertilizers, bulk soil and maize rhizosphere were
      quantified by qPCR before/after fertilization and prior to maize harvest.
      Microbial communities were analyzed via Illumina sequencing of 16S rRNA gene
      fragments amplified from TC-DNA. Compared to inorganic fertilization, manure
      treatments increased relative abundances of all RGs analyzed, integrons and few
      genera affiliated to Bacteroidetes and Firmicutes in bulk soil, while digestate
      increased sul2, tet(W) and intI2. At harvest, treatment effects vanished in bulk
      soil. However, organic fertilizer effects were still detectable in the
      rhizosphere for RGs [manure: intI1, sul1; digestate: tet(W)] and Clostridium
      related sequences (digestates) with increased relative abundance. Our data
      indicated transient organic fertilizer effects on RGs, MGEs and microbial
      community composition in bulk soil with long-term history of digestate or manure
      application.

PMID- 29462311
TI  - Device orientation of a leadless pacemaker and subcutaneous implantable
      cardioverter-defibrillator in canine and human subjects and the effect on
      intrabody communication.
AB  - Aims: The development of communicating modular cardiac rhythm management systems
      relies on effective intrabody communication between a subcutaneous implantable
      cardioverter-defibrillator (S-ICD) and a leadless pacemaker (LP), using conducted
      communication. Communication success is affected by the LP and S-ICD orientation.
      This study is designed to evaluate the orientation of the LP and S-ICD in canine
      subjects and measure success and threshold of intrabody communication. To gain
      more human insights, we will explore device orientation in LP and S-ICD patients.
      Methods and results: Canine subjects implanted with a prototype S-ICD and LP
      (both Boston Scientific, MA, USA) with anterior-posterior fluoroscopy images were
      included in this analysis. For comparison, a retrospective analysis of human S
      ICD and LP patients was performed. The angle of the long axis of the LP towards
      the vertical axis of 0 degrees , and distance between the coil and LP were
      measured. Twenty-three canine subjects were analysed. Median angle of the LP was
      29 degrees  and median distance of the S-ICD coil to LP was 0.8 cm. All canine
      subjects had successful communication. The median communicating threshold was 2.5
      V. In the human retrospective analysis, 72 LP patients and 100 S-ICD patients
      were included. The mean angle of the LP was 56 degrees  and the median distance
      between the S-ICD coil and LP was 4.6 cm. Conclusion: Despite the less favourable
      LP orientation in canine subjects, all communication attempts were successful. In
      the human subjects, we observed a greater and in theory more favourable LP angle
      towards the communication vector. These data suggests suitability of human
      anatomy for conductive intrabody communication.

PMID- 29462313
TI  - Overexpression of the periplasmic nitrate reductase supports anaerobic growth by
      Ensifer meliloti.
AB  - The alfalfa endosymbiont Ensifer meliloti strain1021 is known to be an incomplete
      denitrifier due to its inability to grow anoxically using nitrate as respiratory
      substrate to produce ATP and grow under anoxic conditions. Although this
      bacterium contains and expresses the complete set of denitrification genes
      napEFDABC, nirK, norECBQD and nosRZDFYLX encoding the periplasmic nitrate
      reductase (Nap), Cu-containing nitrite reductase (NirK), c-type nitric oxide
      (cNor) and nitrous oxide reductase (Nos), respectively, the reasons of its
      inability to grow under anoxic conditions are still very poorly understood. In
      the present study, we have constructed an E. meliloti strain overexpressing
      napEFDABC genes (Nap+) and demonstrated that this strain is able to grow through
      anaerobic nitrate respiration. Furthermore, Nap+ showed increased NapC levels as
      well as Nap, Nir and cNor activities and higher capacity to produce NO and N2O
      compared to wild-type cells. These results suggest that the inability of E.
      meliloti to grow under anaerobic conditions using nitrate as electron acceptor is
      attributable to a limitation in the expression of the periplasmic nitrate
      reductase.

PMID- 29462312
TI  - MYO9A deficiency in motor neurons is associated with reduced neuromuscular agrin
      secretion.
AB  - Congenital myasthenic syndromes (CMS) are a group of rare, inherited disorders
      characterized by compromised function of the neuromuscular junction, manifesting
      with fatigable muscle weakness. Mutations in MYO9A were previously identified as
      causative for CMS but the precise pathomechanism remained to be characterized. On
      the basis of the role of MYO9A as an actin-based molecular motor and as a
      negative regulator of RhoA, we hypothesized that loss of MYO9A may affect the
      neuronal cytoskeleton, leading to impaired intracellular transport. To
      investigate this, we used MYO9A-depleted NSC-34 cells (mouse motor neuron-derived
      cells), revealing altered expression of a number of cytoskeletal proteins
      important for neuron structure and intracellular transport. On the basis of these
      findings, the effect on protein transport was determined using a vesicular
      recycling assay which revealed impaired recycling of a neuronal growth factor
      receptor. In addition, an unbiased approach utilizing proteomic profiling of the
      secretome revealed a key role for defective intracellular transport affecting
      proper protein secretion in the pathophysiology of MYO9A-related CMS. This also
      led to the identification of agrin as being affected by the defective transport.
      Zebrafish with reduced MYO9A orthologue expression were treated with an
      artificial agrin compound, ameliorating defects in neurite extension and
      improving motility. In summary, loss of MYO9A affects the neuronal cytoskeleton
      and leads to impaired transport of proteins, including agrin, which may provide a
      new and unexpected treatment option.

PMID- 29462314
TI  - Occurrence of the mobile colistin resistance gene mcr-3 in Escherichia coli from
      household pigs in rural areas.

PMID- 29462315
TI  - Overexpression of Stenotrophomonas maltophilia major facilitator superfamily
      protein MfsA increases resistance to fluoroquinolone antibiotics.
AB  - Background: Stenotrophomonas maltophilia is an opportunistic human pathogen
      causing nosocomial infections worldwide. S. maltophilia infection is of
      particular concern due to its inherent resistance to currently used antibiotics.
      Proton motive force-driven transporters of the major facilitator superfamily
      frequently contribute to the efflux of substances, including antibiotics, across
      cell membranes. Methods: An mfsA expression plasmid (pMfsA) was constructed and
      transferred into bacterial strains by electroporation. The antibiotic
      susceptibility levels of S. maltophilia strains were determined using standard
      methods. Results and conclusions: S. maltophilia MfsA is an efflux pump
      associated with paraquat resistance. We show here that plasmid-mediated
      overexpression of mfsA in WT S. maltophilia K279a increased resistance not only
      to paraquat but also to second-generation fluoroquinolone antibiotics, i.e.
      ciprofloxacin, norfloxacin, levofloxacin and ofloxacin. Ciprofloxacin was used as
      a representative drug. Addition of the proton motive force inhibitor carbonyl
      cyanide-m-chlorophenylhydrazone increases susceptibility to ciprofloxacin. Taken
      together these results suggest that MsfA is a novel fluoroquinolone efflux pump
      of S. maltophilia. Moreover, heterologous expression of mfsA in other Gram
      negative pathogenic bacteria conferred resistance to paraquat as well as to
      fluoroquinolones. Thus, if this determinant was horizontally transferred, it
      could cause the spread of fluoroquinolone resistance among bacterial species.

PMID- 29462316
TI  - Characterization of Flunitrazolam, a New Designer Benzodiazepine, in Oral Fluid
      After a Controlled Single Administration.

PMID- 29462317
TI  - Evaluation of microribonucleic acids as potential biomarkers in the bicuspid
      aortic valve-associated aortopathy.
AB  - OBJECTIVES: We aimed to evaluate the impact of microRNAs to predict the bicuspid
      aortic valve (BAV)-associated aortopathy. METHODS: Sixty-three BAV patients (mean
      age 47 +/- 11 years, 92% men) with root dilatation, who underwent aortic valve +/
      proximal aortic surgery (mean post-AVR follow-up 10.3 +/- 6.9 years) were
      included. The BAV aortopathy entities were categorized in the 'less dilated'
      (aortic root <50 mm) and 'severely dilated' (aortic root >=50 mm) aorta. Several
      microRNAs were assessed using polymerase chain reaction. End-points were the
      correlation between microRNAs and severity of aortopathy/prevalence of adverse
      aortic events. RESULTS: Circulating levels of miR-17 and miR-106a were strongly
      correlated (r = 0.84, P < 0.001). Our analysis yielded significantly higher
      values of miR-17 (delta Ct 2.09 +/- 0.64 vs delta Ct 1.68 +/- 0.64, P = 0.02) and
      miR-106a (delta Ct 5.88 +/- 0.43 vs delta Ct 5.61 +/- 0.60, P = 0.046) in BAV
      patients with the less dilated versus the severely dilated aorta. miR-17 (delta
      Ct 1.51 +/- 0.73 vs delta Ct 2.00 +/- 0.61, P = 0.02) and miR-106a (delta Ct 5.39
      +/- 0.69 vs delta Ct 5.85 +/- 0.44, P = 0.007) were significantly downregulated
      in BAV patients who experienced adverse aortic events. CONCLUSIONS: Expression of
      circulating miR-17 and miR-106a in the BAV root phenotype patients correlates
      with the severity of aortopathy and the risk of adverse aortic events. MicroRNAs
      have the potential to serve as biomarkers in the BAV-associated aortopathy.

PMID- 29462318
TI  - Reply to Nevez et al.

PMID- 29462319
TI  - Cell-free fetal DNA testing in singleton IVF conceptions.
AB  - STUDY QUESTION: Are fetal fraction, test failure rate and positive predictive
      value (PPV) of cell-free fetal DNA (cffDNA) testing different in singleton IVF
      conceptions compared to spontaneous conceptions? SUMMARY ANSWER: Fetal fraction
      is significantly lower; test failure rate is higher and PPV of cffDNA testing is
      lower in singleton pregnancies conceived by IVF than those conceived
      spontaneously. WHAT IS ALREADY KNOWN: cffDNA testing, which analyses circulating
      cffDNA in maternal blood, has very high accuracy for detection of trisomy 21 in
      the general obstetric population. Focused and conclusive evidence regarding the
      test characteristics of cffDNA testing in IVF conceived pregnancies is lacking.
      STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study including
      spontaneously and IVF conceived singleton pregnancies collected consecutively
      between April 2013 and November 2016. A total of 4633 spontaneously conceived and
      992 IVF pregnancies were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: The
      study was performed at an obstetric and gynecological ultrasound clinic in
      Melbourne, Australia. Participants had screening for trisomies 21, 18 and 13, as
      well as sex chromosome aneuploidies (SCA) performed with cffDNA testing after 10
      weeks' gestation. Multivariate regression analysis was used to determine
      significant predictors of logarithmically transformed fetal fraction and test
      failure. Comparison of test characteristics between study groups was performed
      adopting a significance level of 5%. MAIN RESULTS AND THE ROLE OF CHANCE: Median
      fetal fraction was lower (10.3% [interquartile range (IQR), 7.7-13.5] versus
      11.9% [IQR, 9.1-15.0]; P = 0.005), test failure rate was higher (5.2 versus 2.2%;
      P < 0.001) and positive predictive value (PPV) for trisomies 18, 13 and SCA was
      poorer in IVF pregnancies compared to those spontaneously conceived. Multivariate
      linear regression analysis demonstrated that IVF conception, increased BMI,
      earlier gestational age and South and East Asian ethnicities were independent
      predictors of lower fetal fraction. Multiple logistic regression analysis found
      IVF conception and increased BMI to be independently associated with test
      failure. PPV was high for trisomy 21 in IVF conception (100.0%), but was lower
      for other trisomies when compared with the non-IVF population. LIMITATIONS
      REASONS FOR CAUTION: IVF details were unascertainable for 210 cases, as the
      information was not available through our data collection points. Inability to
      karyotype some cases at high-risk for SCA, due to patients' choice, and the
      occurrence of miscarriages and terminations, resulted in the exclusion of high
      risk cases when calculating PPV. Pregnancy outcomes were not available in low
      risk pregnancies and negative predictive values could not be calculated. WIDER
      IMPLICATIONS OF THE FINDINGS: The limitations revealed by this work should be
      taken into account during pre-test counseling in pregnant women who conceive by
      IVF. STUDY FUNDING/COMPETING INTEREST(S): No external source of financial support
      was provided for this research. The authors report no conflicts of interest.

PMID- 29462320
TI  - Air Quality Inside Police Drug Safes and Drug Storage Areas.
AB  - Storage of drug-based evidence inside sealed safes may allow chemical vapors to
      accumulate, creating concerns of drug exposure by inhalation, or the possibility
      of cross-contamination of drug evidence. Air samples were taken from inside eight
      drug safes and one small storage room at nine city and country police stations,
      as well as a large centralized drug evidence storage vault, in New South Wales
      (NSW), Australia. Sorbent tubes containing charcoal were used to determine
      whether any drug residues could be detected in the air, and to identify the types
      of chemicals present. Carbon traps were extracted and analyzed by LC-MS-MS for a
      suite of 22 licit and illicit drug residues and 2 metabolites. Carbon traps and
      SPME fibers were also analyzed by GC-MS for general volatile organic compound
      (VOC) residues. No detectable drug residues, either as airborne dust or vapor,
      were found in the safes, the storage room or the large central repository vault.
      No drugs were detected in any of the 34 urine samples collected at 8 of the 10
      sampling locations, while only one of the five hair samples was positive for
      cocaine (9 pg/mg) provided by police exhibit officers at 3 of the 10 sampling
      locations. VOC analysis identified a variety of solvents associated with drug
      manufacture, plasticisers, personal care products and volatiles associated with
      plants such as cannabis. The results indicate that strong chemical odours
      emanating from drug safes are unlikely to be drug residues due to low volatility
      of drugs, and are more likely VOCs associated with their manufacture or from
      plant growing operations. Consideration should be given to the quality of air
      flow in rooms in which safes are housed and the use of air filtering inside safes
      to reduce the likelihood of VOC accumulation, and therefore the risk of human
      exposure.

PMID- 29462321
TI  - Discordant Umbilical Cord Drug Testing Results in Monozygotic Twins.
AB  - Our laboratory received segments of umbilical cord that originated from identical
      twins for routine toxicology analysis. The specimens were analyzed multiple times
      by liquid chromatography tandem mass spectrometry. The umbilical cord from
      newborn #1 was positive for hydromorphone only (1.06 ng/g), and the umbilical
      cord from newborn #2 was positive for hydromorphone (0.81 ng/g) and
      benzoylecgonine (5.41 ng/g). The hydromorphone results are consistent with
      maternal administration of hydromorphone; however, the cause of the discrepant
      benzoylecgonine results in the umbilical cords from the identical twins is
      unknown.

PMID- 29462322
TI  - Primary resistance to integrase strand transfer inhibitors in patients infected
      with diverse HIV-1 subtypes in sub-Saharan Africa.
AB  - Objectives: To investigate the prevalence and patterns of major and accessory
      resistance mutations associated with integrase strand transfer inhibitors
      (INSTIs), across diverse HIV-1 subtypes in sub-Saharan Africa. Methods: pol gene
      sequences were obtained using Illumina next-generation sequencing from 425 INSTI
      naive HIV-infected adults from Kenya (21.2%), Nigeria (7.3%), South Africa
      (22.8%), Uganda (25.2%) and Zambia (23.5%). Drug resistance interpretation was
      based on the IAS 2017 mutation list and accessory mutations from Stanford HIVdb
      with resistance penalty scores of >=10 to at least 1 INSTI. Resistance was
      further classified based on sensitivity thresholds of >=20% (Sanger sequencing)
      and 1%-20% for low-frequency variants (next-generation sequencing). Results: Of
      425 genotypes, 48.7% were subtype C, 28.5% A, 10.1% D, 2.8% G and 9.9% were
      recombinants. Major INSTI resistance mutations were detected only at <20%
      threshold, at a prevalence of 2.4% (2.5% in subtype A, 2.4% C, 0% D, 8.3% G and
      2.4% in recombinants) and included T66A/I (0.7%), E92G (0.5%), Y143C/S (0.7%),
      S147G (0.2%) and Q148R (0.5%). Accessory mutations occurred at a prevalence of
      15.1% at the >=20% threshold (23.1% in subtype A, 8.7% C, 11.6% D, 25% G and
      23.8% in recombinants), and included L74I/M (10.4%), Q95K (0.5%), T97A (4%),
      E157Q (0.7%) and G163R/K (0.7%). Conclusions: Major INSTI resistance mutations
      were rare and only occurred at low-level resistance detection thresholds. INSTI
      based regimens are expected to be effective across the different major HIV-1
      subtypes in the region.

PMID- 29462323
TI  - Longitudinal analysis strategies for modelling epigenetic trajectories.
AB  - Background: DNA methylation levels are known to vary over time, and modelling
      these trajectories is crucial for our understanding of the biological relevance
      of these changes over time. However, due to the computational cost of fitting
      multilevel models across the epigenome, most trajectory modelling efforts to date
      have focused on a subset of CpG sites identified through epigenome-wide
      association studies (EWAS) at individual time-points. Methods: We propose using
      linear regression across the repeated measures, estimating cluster-robust
      standard errors using a sandwich estimator, as a less computationally intensive
      strategy than multilevel modelling. We compared these two longitudinal
      approaches, as well as three approaches based on EWAS (associated at baseline, at
      any time-point and at all time-points), for identifying epigenetic change over
      time related to an exposure using simulations and by applying them to blood DNA
      methylation profiles from the Accessible Resource for Integrated Epigenomics
      Studies (ARIES). Results: Restricting association testing to EWAS at baseline
      identified a less complete set of associations than performing EWAS at each time
      point or applying the longitudinal modelling approaches to the full dataset.
      Linear regression models with cluster-robust standard errors identified similar
      sets of associations with almost identical estimates of effect as the multilevel
      models, while also being 74 times more efficient. Both longitudinal modelling
      approaches identified comparable sets of CpG sites in ARIES with an association
      with prenatal exposure to smoking (>70% agreement). Conclusions: Linear
      regression with cluster-robust standard errors is an appropriate and efficient
      approach for longitudinal analysis of DNA methylation data.

PMID- 29462324
TI  - Endometriosis induces gut microbiota alterations in mice.
AB  - STUDY QUESTION: What happens to the gut microbiota during development of murine
      endometriosis? SUMMARY ANSWER: Mice with the persistence of endometrial lesions
      for 42 days develop a distinct composition of gut microbiota. WHAT IS KNOWN
      ALREADY: Disorders in the immune system play fundamental roles in changing the
      intestinal microbiota. No study has used high-throughput DNA sequencing to show
      how endometriosis changes the gut microbiota, although endometriosis is
      accompanied by abnormal cytokine expression and immune cell dysfunction. STUDY
      DESIGN, SIZE, DURATION: This study includes a prospective and randomized
      experiment on an animal endometriosis model induced via the intraperitoneal
      injection of endometrial tissues. PARTICIPANTS/MATERIALS, SETTING, METHODS: The
      mice were divided into endometriosis and mock groups and were sacrificed at four
      different time points for model confirmation and fecal sample collection. To
      detect gut microbiota, 16S ribosomal-RNA gene sequencing was performed. Alpha
      diversity was used to analyze the complexity and species diversity of the samples
      through six indices. Beta diversity analysis was utilized to evaluate the
      differences in species complexity. Principal coordinate analysis and unweighted
      pair-group method with arithmetic means clustering were performed to determine
      the clustering features. The microbial features differentiating the fecal
      microbiota were characterized by linear discriminant analysis effect size method.
      MAIN RESULTS AND THE ROLE OF CHANCE: The endometriosis and mock mice shared
      similar diversity and richness of gut microbiota. However, different compositions
      of gut microbiota were detected 42 days after the modeling. Among the
      discriminative concrete features, the Firmicutes/Bacteroidetes ratio was elevated
      in mice with endometriosis, indicating that endometriosis may induce dysbiosis.
      Bifidobacterium, which is known as a commonly used probiotic, was also increased
      in mice with endometriosis. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR
      CAUTION: More control groups should be further studied to clarify the specificity
      of the dysbiosis induced by endometriosis. This study was performed only on mice.
      Thus, additional data acquired from patients with endometriosis are needed in
      future research. We only detected the changes of gut microbiota at 42 days after
      the modeling, while the long-term effect of endometriosis on gut microbiota
      remains poorly understood. Moreover, we only revealed a single effect of
      endometriosis on gut microbiota. WIDER IMPLICATIONS OF THE FINDINGS: This study
      provided the first comprehensive data on the association of endometriosis and gut
      microbiota from high-throughput sequencing technology. The gut microbiota changed
      with the development of endometriosis in a murine model. The communication
      between the host and the gut microbiota is bidirectional, and further studies
      should be performed to clarify their relationship. STUDY FUNDING/COMPETING
      INTEREST(S): This research was supported by Grant (81571417) from the National
      Science Foundation of China and Grant (2015GSF118092) from the Technology
      Development Plan of Shandong Province. The authors report no conflict of
      interest.

PMID- 29462325
TI  - Unpacking the black box of improvement.
AB  - During the Salzburg Global Seminar Session 565-'Better Health Care: How do we
      learn about improvement?', participants discussed the need to unpack the 'black
      box' of improvement. The 'black box' refers to the fact that when quality
      improvement interventions are described or evaluated, there is a tendency to
      assume a simple, linear path between the intervention and the outcomes it yields.
      It is also assumed that it is enough to evaluate the results without
      understanding the process of by which the improvement took place. However,
      quality improvement interventions are complex, nonlinear and evolve in response
      to local settings. To accurately assess the effectiveness of quality improvement
      and disseminate the learning, there must be a greater understanding of the
      complexity of quality improvement work. To remain consistent with the language
      used in Salzburg, we refer to this as 'unpacking the black box' of improvement.
      To illustrate the complexity of improvement, this article introduces four quality
      improvement case studies. In unpacking the black box, we present and demonstrate
      how Cynefin framework from complexity theory can be used to categorize and
      evaluate quality improvement interventions. Many quality improvement projects are
      implemented in complex contexts, necessitating an approach defined as 'probe
      sense-respond'. In this approach, teams experiment, learn and adapt their changes
      to their local setting. Quality improvement professionals intuitively use the
      probe-sense-respond approach in their work but document and evaluate their
      projects using language for 'simple' or 'complicated' contexts, rather than the
      'complex' contexts in which they work. As a result, evaluations tend to ask 'How
      can we attribute outcomes to the intervention?', rather than 'What were the
      adaptations that took place?'. By unpacking the black box of improvement,
      improvers can more accurately document and describe their interventions, allowing
      evaluators to ask the right questions and more adequately evaluate quality
      improvement interventions.

PMID- 29462326
TI  - Secreted frizzled-related protein 2 (SFRP2) expression promotes lesion
      proliferation via canonical WNT signaling and indicates lesion borders in
      extraovarian endometriosis.
AB  - STUDY QUESTION: What is the role of SFRP2 in endometriosis? SUMMARY ANSWER: SFRP2
      acts as a canonical WNT/CTNNB1 signaling agonist in endometriosis, regulating
      endometriosis lesion growth and indicating endometriosis lesion borders together
      with CTNNB1 (also known as beta catenin). WHAT IS KNOWN ALREADY: Endometriosis is
      a common, chronic disease that affects women of reproductive age, causing pain
      and infertility, and has significant economic impact on national health systems.
      Despite extensive research, the pathogenesis of endometriosis is poorly
      understood, and targeted medical treatments are lacking. WNT signaling is
      dysregulated in various human diseases, but its role in extraovarian
      endometriosis has not been fully elucidated. STUDY DESIGN, SIZE, DURATION: We
      evaluated the significance of WNT signaling, and especially secreted frizzled
      related protein 2 (SFRP2), in extraovarian endometriosis, including peritoneal
      and deep lesions. The study design was based on a cohort of clinical samples
      collected by laparoscopy or curettage and questionnaire data from healthy
      controls and endometriosis patients. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Global gene expression analysis in human endometrium (n = 104) and endometriosis
      (n = 177) specimens from 47 healthy controls and 103 endometriosis patients was
      followed by bioinformatics and supportive qPCR analyses. Immunohistochemistry,
      Western blotting, primary cell culture and siRNA knockdown approaches were used
      to validate the findings. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 220 WNT
      signaling and CTNNB1 target genes analysed, 184 genes showed differential
      expression in extraovarian endometriosis (P < 0.05) compared with endometrium
      tissue, including SFRP2 and CTNNB1. Menstrual cycle-dependent regulation of WNT
      genes observed in the endometrium was lost in endometriosis lesions, as shown by
      hierarchical clustering. Immunohistochemical analysis indicated that SFRP2 and
      CTNNB1 are novel endometriosis lesion border markers, complementing
      immunostaining for the known marker CD10 (also known as MME). SFRP2 and CTNNB1
      localized similarly in both the epithelium and stroma of extraovarian
      endometriosis tissue, and interestingly, both also indicated an additional
      distant lesion border, suggesting that WNT signaling is altered in the
      endometriosis stroma beyond the primary border indicated by the known marker
      CD10. SFRP2 expression was positively associated with pain symptoms experienced
      by patients (P < 0.05), and functional loss of SFRP2 in extraovarian
      endometriosis primary cell cultures resulted in decreased cell proliferation (P <
      0.05) associated with reduced CTNNB1 protein expression (P = 0.05). LIMITATIONS
      REASONS FOR CAUTION: SFRP2 and CTNNB1 improved extraovarian endometriosis lesion
      border detection in a relatively small cohort (n = 20), although larger studies
      with different endometriosis subtypes in variable cycle phases and under hormonal
      medication are required. WIDER IMPLICATIONS OF THE FINDINGS: The highly expressed
      SFRP2 and CTNNB1 improve endometriosis lesion border detection, which can have
      clinical implications for better visualization of endometriosis lesions over
      CD10. Furthermore, SFRP2 acts as a canonical WNT/CTNNB1 signaling agonist in
      endometriosis and positively regulates endometriosis lesion growth, suggesting
      that the WNT pathway may be an important therapeutic target for endometriosis.
      STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Academy of
      Finland and by Tekes: Finnish Funding Agency for Innovation. The authors have no
      conflict of interest to declare.

PMID- 29462328
TI  - Different genomic changes underlie adaptive evolution in populations of
      contrasting history.

PMID- 29462327
TI  - Risk factors for spinal cord ischaemia after thoracic endovascular aortic repair.
AB  - OBJECTIVES: Spinal cord ischaemia (SCI) is a serious complication of thoracic
      endovascular aortic repair (TEVAR). The purpose of this study was to assess the
      incidence, risk factors, clinical manifestations of SCI after TEVAR and which
      type of patients could benefit from cerebrospinal fluid drainage. METHODS: A
      retrospective review was conducted for 175 patients who underwent TEVAR from
      January 2008 to July 2014. All patients were divided into groups with and without
      SCI, and they were compared to identify significant risk factors for SCI.
      RESULTS: The incidence of SCI after TEVAR including paraplegia and paraparesis
      was 6.9%. SCI usually occurred within 24 h, but delayed SCI was observed after 5
      days in 1 patient. In all patients with SCI, we tried to increase the blood
      pressure to improve spinal perfusion. Three patients recovered completely, and
      the 6 patients with some remaining neurological deficit included 3 with motion
      against gravity and bladder dysfunction and the 3 remaining patients with only
      bladder dysfunction. Three patients did not recover. In our study, significant
      risk factors for SCI were as follows: rupture, shaggy aorta, chronic obstructive
      pulmonary disease, 1-stage procedure, the coverage of more than 9 segments, the
      coverage from Th8 to Th12, minimum of postoperative haemoglobin and the number of
      postoperative patent segmental arteries. CONCLUSIONS: Sufficient perioperative
      care should be given to high-risk patients who have endografts that cover more
      than 9 segments and endografts that cover segments from Th8 to Th12. Adequate
      haemoglobin levels and mean arterial pressure are needed to provide sufficient
      spinal cord perfusion.

PMID- 29462329
TI  - Association of job sectors with type 2 diabetes mellitus, hypercholesterolemia
      and obesity: a cross-sectional study from the Malaysian Cohort (TMC) project.
AB  - Background: The investigation of risk factors of cardiovascular disease (e.g.,
      major endocrine, nutritional and metabolic diseases) across job sectors is useful
      for targeted public health intervention. This study examined the occurrence of
      type 2 diabetes mellitus (T2DM), hypercholesterolemia and obesity in 21 job
      sectors in the general population. Methods: A baseline cross-sectional analysis
      of the Malaysian Cohort was conducted, which included 105 391 adults. Multiple
      logistic regression analyses were conducted for these three diseases across 20
      job sectors compared with the unemployed/homemaker sector. Results: The
      prevalence of T2DM, hypercholesterolemia and obesity was 16.7%, 38.8% and 33.3%,
      respectively. The Accommodation & Food Service Activities and Transportation &
      Storage sectors had significantly higher odds for T2DM (adjusted [adj.]
      prevalence odds ratio [POR] 1.18, p=0.007 and adj. POR 1.15, p=0.008,
      respectively). No job sector had significantly higher odds for
      hypercholesterolemia compared with the unemployed/homemaker sector. Only the
      Accommodation & Food Service Activities sector had significantly higher odds for
      obesity (adj. POR 1.17, p<=0.001). Conclusions: Many job sectors were
      significantly associated with lower odds of having these three diseases when
      compared with the unemployed/homemaker sector. These differing associations
      between diverse job sectors and these diseases are important for public health
      intervention initiatives and prioritization.

PMID- 29462331
TI  - Does a low-income urban population practise healthy dietary habits?
AB  - Background: The purpose of this study was to identify the unhealthy dietary
      habits and practices in a low-income community in an urban area and determine the
      associated factors. Methods: A cross-sectional survey was conducted in a low
      income housing area in Kuala Lumpur, Malaysia. Data were collected using a
      questionnaire via face-to-face interviews by trained enumerators in order to
      obtain details on sociodemographic characteristics and dietary practices.
      Results: Descriptive statistics showed that 86.7% of the respondents in the low
      income community consumed fruit and vegetables less than five times per day,
      11.7% consumed carbonated and sweetened drinks more than twice per day and about
      25% consumed fast food more than four times per month. In total, 65.2% (n=945)
      did not have healthy dietary practices. Binary logistic regression showed that
      age, education and ethnicity were significant predictors of unhealthy dietary
      practices among the low-income community. Those in the 30-59 years age group had
      higher odds (odds ratio 1.65, p=0.04) of practising an unhealthy diet as compared
      with those older than 60 years of age. Conclusion: Unhealthy dietary practices
      were found to be common among the low-income group living in an urban area.
      Healthy lifestyle intervention should be highlighted so that it can be adopted in
      the low-income group.

PMID- 29462332
TI  - Molecular Data Support an Early Shift to an Intermediate-Light Niche in the
      Evolution of Mammals.
AB  - The visual ability and associated photic niche of early mammals is debated. The
      theory that ancestral mammals were nocturnal is supported by diverse adaptations.
      However, others argue that photopigment repertoires of early mammals are more
      consistent with a crepuscular niche, and support for this also comes from
      inferred spectral tuning of middle/long wavelength-sensitive (M/LWS) opsin
      sequences. Functional studies have suggested that the M/LWS pigment in the
      ancestor of Mammalia was either red- or green-sensitive; however, these were
      based on outdated phylogenies with key lineages omitted. By performing the most
      detailed study to date of middle/long-wave mammalian color vision, we provide the
      first experimental evidence that the M/LWS pigment of amniotes underwent a 9-nm
      spectral shift towards shorter wavelengths in the Mammalia ancestor, exceeding
      predictions from known critical sites. Our results suggest early mammals were
      yellow-sensitive, possibly representing an adaptive trade-off for both
      crepuscular (twilight) and nocturnal (moonlight) niches.

PMID- 29462330
TI  - Cell surface chondroitin sulphate proteoglycan 4 (CSPG4) binds to the basement
      membrane heparan sulphate proteoglycan, perlecan, and is involved in cell
      adhesion.
AB  - Chondroitin sulphate proteoglycan 4 (CSPG4) is a cell surface proteoglycan highly
      expressed by tumour, perivascular and oligodendrocyte cells and known to be
      involved cell adhesion and migration. This study showed that CSPG4 was present as
      a proteoglycan on the cell surface of two melanoma cell lines, MM200 and Me1007,
      as well as shed into the conditioned medium. CSPG4 from the two melanoma cell
      lines differed in the amount of chondroitin sulphate (CS) decoration, as well as
      the way the protein core was fragmented. In contrast, the CSPG4 expressed by a
      colon carcinoma cell line, WiDr, was predominantly as a protein core on the cell
      surface lacking glycosaminoglycan (GAG) chains. This study demonstrated that
      CSPG4 immunopurified from the melanoma cell lines formed a complex with perlecan
      synthesized by the same cultured cells. Mechanistic studies showed that CSPG4
      bound to perlecan via hydrophobic protein-protein interactions involving multiple
      sites on perlecan including the C-terminal region. Furthermore, this study
      revealed that CSPG4 interacted with perlecan to support cell adhesion and actin
      polymerization. Together these data suggest a novel mechanism by which CSPG4
      expressing cells might attach to perlecan-rich matrices so as those found in
      connective tissues and basement membranes.

PMID- 29462333
TI  - High positive end-expiratory pressure during ex vivo lung perfusion: recruiting
      rejected donor lungs.
AB  - We present an innovative method for recruiting clinically rejected donor lungs
      using positive end-expiratory pressure titration during ex vivo lung perfusion.
      Currently, ex vivo lung perfusion protocols are using a standard positive end
      expiratory pressure of 5 cmH2O for all cases. Individualized positive end
      expiratory pressure titration combined with recruitment manoeuvres has been found
      to significantly improve pulmonary functions in mechanically ventilated patients.
      Applying this concept to ex vivo lung perfusion may be helpful in increasing the
      conversion rate for transplant suitability.

PMID- 29462336
TI  - Erratum to A beta-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced
      Hyperpermeability in Ileum From Patients With Crohn's Disease and Control
      Subjects.

PMID- 29462335
TI  - Five-year experience using the Lung Allocation Score: the Munich Lung Transplant
      Group.
AB  - OBJECTIVES: The Lung Allocation Score (LAS) was implemented in Germany on 10
      December 2011 after demonstrating favourable outcomes in the USA since its
      introduction in 2005. There are only limited and short-term data on the effect of
      the LAS on lung transplantation programmes in Germany. The purpose of this study
      was to analyse our 5-year single-centre experience with the LAS within the
      influential area of the Eurotransplant Foundation (ET). METHODS: After
      implementation of the LAS until December 2016, 294 patients underwent a single
      lung transplantation or a bilateral sequential lung transplantation for end-stage
      lung disease at our centre. Patients were divided into 4 groups according to
      their primary diagnosis. The Kaplan-Meier analyses of survival probabilities were
      performed to compare types of transplant procedures, underlying diagnoses and the
      LASs at the time of transplantation. Waitlist characteristics, transplant
      procedures and up to 5-year post-transplant outcomes were analysed. RESULTS: The
      proportion of lung transplants performed for interstitial lung disease increased
      over time from 27% in 2012 to 54% in 2016 (P = 0.056). At the same time, the
      proportion of patients with chronic obstructive pulmonary disease undergoing lung
      transplantation declined over the 5-year period, i.e. from 29% in 2011 to 19% in
      2016 (P = 0.029). Overall waiting times of transplanted patients were
      approximately 200 days and did not markedly change over time. There was an
      increasing proportion of chronic obstructive pulmonary disease patients on the
      waitlist from 41% in 2011 to 51% in 2016 (P = 0.51). Outcomes were independent of
      the underlying disease entity or the LAS. Bilateral sequential lung
      transplantation was associated with a better long-term survival probability when
      compared with a single-lung transplantation (P < 0.001). CONCLUSIONS: Our centre
      specific 5-year experience confirms previous findings demonstrating that the LAS
      is a well-established tool for the selection of lung transplant candidates,
      respecting urgency and prognostic transplant benefit in a disease-specific
      manner. However, the LAS did not shorten overall waiting times in transplanted
      patients. Further long-term and multicentre data with respect to differential
      transplant centre activities have to be gathered for further evaluation.

PMID- 29462334
TI  - Left frontal hub connectivity delays cognitive impairment in autosomal-dominant
      and sporadic Alzheimer's disease.
AB  - Patients with Alzheimer's disease vary in their ability to sustain cognitive
      abilities in the presence of brain pathology. A major open question is which
      brain mechanisms may support higher reserve capacity, i.e. relatively high
      cognitive performance at a given level of Alzheimer's pathology. Higher
      functional MRI-assessed functional connectivity of a hub in the left frontal
      cortex is a core candidate brain mechanism underlying reserve as it is associated
      with education (i.e. a protective factor often associated with higher reserve)
      and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no
      study has yet assessed whether such hub connectivity of the left frontal cortex
      supports reserve throughout the evolution of pathological brain changes in
      Alzheimer's disease, including the presymptomatic stage when cognitive decline is
      subtle. To address this research gap, we obtained cross-sectional resting state
      functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55
      controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid
      positive elderly participants, as well as 41 amyloid-negative cognitively normal
      elderly subjects from the German Center of Neurodegenerative Diseases multicentre
      study on biomarkers in sporadic Alzheimer's disease. For each participant, global
      left frontal cortex connectivity was computed as the average resting state
      functional connectivity between the left frontal cortex (seed) and each voxel in
      the grey matter. As a marker of disease stage, we applied estimated years from
      symptom onset in autosomal dominantly inherited Alzheimer's disease and
      cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both
      autosomal dominant and sporadic Alzheimer's disease patients, higher levels of
      left frontal cortex connectivity were correlated with greater education. For
      autosomal dominant Alzheimer's disease, a significant left frontal cortex
      connectivity * estimated years of onset interaction was found, indicating slower
      decline of memory and global cognition at higher levels of connectivity.
      Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on
      cognition was attenuated at higher levels of left frontal cortex connectivity.
      Polynomial regression analysis showed that the trajectory of cognitive decline
      was shifted towards a later stage of Alzheimer's disease in patients with higher
      levels of left frontal cortex connectivity. Together, our findings suggest that
      higher resilience against the development of cognitive impairment throughout the
      early stages of Alzheimer's disease is at least partially attributable to higher
      left frontal cortex-hub connectivity.

PMID- 29462337
TI  - Repeated Systemic Treatment with Rapamycin Affects Behavior and Amygdala Protein
      Expression in Rats.
AB  - Background: Clinical data indicate that therapy with small-molecule
      immunosuppressive drugs is frequently accompanied by an incidence rate of
      neuropsychiatric symptoms. In the current approach, we investigated in rats
      whether repeated administration of rapamycin, reflecting clinical conditions of
      patients undergoing therapy with this mammalian target of rapamycin inhibitor,
      precipitates changes in neurobehavioral functioning. Methods: Male adult Dark
      Agouti rats were daily treated with i.p. injections of rapamycin (1, 3 mg/kg) or
      vehicle for 8 days. On days 6 and 7, respectively, behavioral performance in the
      Elevated Plus-Maze and the Open-Field Test was evaluated. One day later, amygdala
      tissue and blood samples were taken to analyze protein expression ex vivo.
      Results: The results show that animals treated with rapamycin displayed
      alterations in Elevated Plus-Maze performance with more pronounced effects in the
      higher dose group. Besides, an increase in glucocorticoid receptor density in the
      amygdala was seen in both treatment groups even though p-p70 ribosomal S6 kinase
      alpha, a marker for mammalian target of rapamycin functioning, was not affected.
      Protein level of the neuronal activity marker c-Fos was again only elevated in
      the higher dose group. Importantly, effects occurred in the absence of acute
      peripheral neuroendocrine changes. Conclusions: Our findings indicate that
      anxiety-related behavior following rapamycin treatment was not directly
      attributed to mTOR-dependent mechanisms or stress but rather due to
      hyperexcitability of the amygdala together with glucocorticoid receptor-regulated
      mechanism(s) in this brain region. Together, the present results support the
      contention that subchronic treatment with rapamycin may induce neurobehavioral
      alterations in healthy, naive subjects. We here provide novel insights in central
      effects of systemic rapamycin in otherwise healthy subjects but also raise the
      question whether therapy with this drug may have detrimental effects on patients'
      neuropsychological functioning during immune therapy.

PMID- 29462338
TI  - Ammonium intensifies CAM photosynthesis and counteracts drought effects by
      increasing malate transport and antioxidant capacity in Guzmania monostachia.
AB  - Guzmania monostachia (Bromeliaceae) is a tropical epiphyte capable of up
      regulating crassulacean acid metabolism (CAM) in its photosynthetic tissues in
      response to changing nutrient and water availability. Previous studies have shown
      that under drought there is a gradient of increasing CAM expression from the
      basal (youngest) to the apical (oldest) portion of the leaves, and additionally
      that nitrogen deficiency can further increase CAM intensity in the leaf apex of
      this bromeliad. The present study investigated the inter-relationships between
      nitrogen source (nitrate and/or ammonium) and water deficit in regulating CAM
      expression in G. monostachia leaves. The highest CAM activity was observed under
      ammonium nutrition in combination with water deficit. This was associated with
      enhanced activity of the key enzyme phosphoenolpyruvate carboxylase, elevated
      rates of ATP- and PPi-dependent proton transport at the vacuolar membrane in the
      presence of malate, and increased transcript levels of the vacuolar malate
      channel-encoding gene, ALMT. Water deficit was consistently associated with
      higher levels of total soluble sugars, which were maximal under ammonium
      nutrition, as were the activities of several antioxidant enzymes (superoxide
      dismutase, catalase, ascorbate peroxidase, and glutathione reductase). Thus,
      ammonium nutrition, whilst associated with the highest degree of CAM induction in
      G. monostachia, also mitigates the effects of water deficit by osmotic adjustment
      and can limit oxidative damage in the leaves of this bromeliad under conditions
      that may be typical of its epiphytic habitat.

PMID- 29462339
TI  - A Pilot Study of Neural Correlates of Loss of Control Eating in Children With
      Overweight/Obesity: Probing Intermittent Access to Food as a Means of Eliciting
      Disinhibited Eating.
AB  - Objective: Neural substrates of loss of control (LOC) eating are
      undercharacterized. We aimed to model intermittent access to food to elicit
      disinhibited eating in youth undergoing neuroimaging, given evidence that
      restricted food access may increase subsequent food intake via enhancing reward
      value of food and diminishing eating-related self-control. Methods: Participants
      were 18 preadolescents (aged 9-12 years) who were overweight/obese with recent
      LOC eating (OW-LOC; n = 6); overweight/obese with no history of LOC eating (OW
      CON; n = 5); or non-overweight with no history of LOC eating (NW-CON; n = 7).
      Participants underwent functional magnetic resonance imaging during a simulated
      food restriction paradigm in which they were alternately given restricted or
      unrestricted access to milkshake solutions. Results: There were no significant
      main effects of restricted versus unrestricted access to milkshake flavors. Group
      main effects revealed increased activation for OW-LOC relative to OW-CON in areas
      related to attentional processes (right middle frontal gyrus), inhibitory
      control/attentional shifts (right and left cuneus), and emotion regulation (left
      cingulate gyrus); and for OW-LOC relative to NW-CON in areas related to response
      inhibition (right inferior frontal gyrus). Significant block type * group
      interaction effects were found for the right middle frontal gyrus, left cingulate
      gyrus, and left cuneus, but these appeared to be accounted for primarily by
      group. Discussion: There were clear group differences in neural activity in brain
      regions related to self-regulation during a food restriction paradigm. Elevations
      in these regions among OW-LOC relative to OW-CON and NW-CON, respectively, may
      suggest that youth with LOC eating expended more cognitive effort to regulate
      ingestive behavior.

PMID- 29462341
TI  - Laboratory Evaluation of Commercially Available Platforms to Detect West Nile and
      Zika Viruses From Honey Cards.
AB  - Commercially available assays utilizing antigen or nucleic acid detection
      chemistries provide options for mosquito control districts to screen their
      mosquito populations for arboviruses and make timely operational decisions
      regarding vector control. These assays may be utilized even more advantageously
      when combined with honey-soaked nucleic acid preservation substrate ('honey
      card') testing by reducing or replacing the time- and labor-intensive efforts of
      identifying and processing mosquito pools. We tested artificially inoculated
      honey cards and cards fed upon individually by West Nile virus (WNV) and Zika
      virus (ZIKV)-infected mosquitoes with three assays to compare detection rates and
      the limit of detection for each platform with respect to virus detection of a
      single infected mosquito and quantify the time interval of virus preservation on
      the cards. Assays evaluated included CDC protocols for real-time reverse
      transcriptase polymerase chain reaction (RT-PCR) for WNV and ZIKV, Pro-Lab
      Diagnostics ProAmpRT WNV loop-mediated amplification (LAMP) and ZIKV LAMP assays,
      and the Rapid Analyte Measurement Platform (RAMP) WNV assay. Real-time RT-PCR was
      the most sensitive assay and the most robust to viral RNA degradation over time.
      To maximize the detection of virus, honey cards should be left in the traps <=1 d
      if using LAMP assays and <=3 d if using real-time RT-PCR to detect viruses from
      field samples. The WNV RAMP assay, although effective for pool screening, lacks
      sensitivity required for honey card surveillance. Future studies may determine
      the minimum number of infectious mosquitoes required to feed on a honey card that
      would be reliably detected by the LAMP or RAMP assays.

PMID- 29462340
TI  - Expression patterns of SRB1 and other stress-related genes in Candida albicans
      under oxidative, hyperosmotic and thermal stress.
AB  - Candida albicans, a human fungal pathogen, is able to tolerate certain levels of
      environmental stresses. Its cell wall plays an important role in cellular
      homeostasis, responding to environmental stimuli. SRB1 gene encodes a GDP-mannose
      pyrophosphorylase that catalyzes the formation of the major cell wall component,
      mannan. The exact relationship between SRB1 and various stresses is not yet fully
      understood. In current study, C. albicans SC5314 cells were exposed to oxidative,
      hyperosmotic, and thermal stresses. The expression of SRB1 and related stress
      response genes, HOG1, CAP1, MKC1, and HSP90, was systematically evaluated in
      cells exposed to various levels of stress. In addition, the apoptosis and
      ultrastructural changes of the cells were examined. We found that the expression
      of SRB1 and related stress response genes significantly increased under
      oxidative, hyperosmotic, and thermal stresses, and the increased gene expression
      was correlated with higher percentages of apoptosis and ultrastructural changes
      in C. albicans cells. We propose that protein glycosylation is associated with
      stress response that involves SRB1 in C. albicans. Further in-depth studies of
      SRB1 function should aid our understanding of C. albicans pathogenesis, and
      provide important clues about the development of novel antifungal compounds for
      drug resistant C. albicans.

PMID- 29462342
TI  - Seasonality of acute kidney injury incidence and mortality among hospitalized
      patients.
AB  - Background: Understanding disease seasonality is important for improving clinical
      practice, hospital resource utilization and community-based preventive care.
      However, no studies have investigated the seasonality of acute kidney injury
      (AKI). Methods: In the Tokushukai Medical Database, which includes 38 Japanese
      community hospitals, we identified hospitalized patients with AKI based on the
      Kidney Disease: Improving Global Outcomes serum creatinine criteria from January
      2012 to December 2014. We plotted the number and proportion of patients with AKI
      among hospitalized patients by month of hospital admission. Subgroup analyses
      were conducted by the admission diagnosis category, timing of AKI diagnosis and
      age. We also examined the association between month of hospital admission and
      AKI, adjusting for patient characteristics and AKI risk factors. Finally, we
      assessed seasonal variations in disease severity and 30-day mortality of patients
      with AKI. Results: We identified 81 279 (14.6%) patients with AKI among 555 940
      hospitalized patients. The proportion of patients with AKI was highest in January
      (16.7%) and lowest in June (13.4%). Subgroup analyses suggested that the
      seasonality of AKI incidence was driven by community-acquired AKI associated with
      the admission diagnosis of cardiovascular and pulmonary diseases among older
      patients. The adjusted odds ratio for AKI (January versus June) was 1.24 (95%
      confidence interval, 1.17-1.31). Patients with AKI showed a larger number of
      failing organs in winter, and their 30-day mortality was 16.4% in spring, 14.5%
      in summer, 15.6% in autumn and 18.4% in winter. Conclusion: AKI is more common
      among hospitalized patients and patients with AKI are more severely ill in
      winter.

PMID- 29462344
TI  - Do community pharmacists add value to routine immunization programmes? A review
      of the evidence from the UK.
AB  - Background: Community pharmacies are an important setting for the provision of
      preventative health services in the UK. There has been debate over the value of
      delivering routine immunizations in a pharmacy setting, though government policy
      supports this initiative and in 2015 the first nationally commissioned community
      pharmacy vaccination service was launched for seasonal influenza vaccination. The
      impact of these vaccination services needs to be evaluated to inform future
      policy. Methods: We conducted a comprehensive review of peer-reviewed studies and
      unpublished evaluations of community pharmacy-based vaccination services
      implemented in the UK between 2000 and 2015. We assessed evidence of their impact
      on acceptability, uptake, cost-effectiveness and addressing inequalities.
      Results: We identified 28 evaluations of pharmacy immunization programmes in the
      UK, only three of which were published in peer-reviewed journals. These showed no
      evidence of increased vaccination uptake, and weak evidence of widening access to
      individuals who had not previously been vaccinated. There was good evidence that
      pharmacies were acceptable and convenient venues for vaccination. Cost
      effectiveness was not assessed in any of the included studies. Conclusions: Our
      review challenges an assumption that pharmacy provision of immunizations will
      simultaneously improve patient choice, increase uptake and widen access. These
      are important findings for policy makers.

PMID- 29462346
TI  - A systematic review of economic evaluations of local authority commissioned
      preventative public health interventions in overweight and obesity, physical
      inactivity, alcohol and illicit drugs use and smoking cessation in the United
      Kingdom.
AB  - Background: Since 2013, local authorities in England have been responsible for
      commissioning preventative public health interventions. The aim of this
      systematic review was to support commissioning by collating published data on
      economic evaluations and modelling of local authority commissioned public health
      preventative interventions in the UK. Methods: Following the PRISMA protocol, we
      searched for economic evaluations of preventative intervention studies in four
      different areas: overweight and obesity, physical inactivity, alcohol and illicit
      drugs use and smoking cessation. The systematic review identified studies between
      January 1994 and February 2015, using five databases. We synthesized the studies
      to identify the key methods and examined results of the economic evaluations.
      Results: The majority of the evaluations related to cost-effectiveness, rather
      than cost-benefit analyses or cost-utility analyses. These analyses found
      preventative interventions to be cost effective, though the context of the
      interventions differed between the studies. Conclusions: Preventative public
      health interventions in general are cost-effective. There is a need for further
      studies to support justification of continued and/or increased funding for public
      health interventions. There is much variation between the types of economically
      evaluated preventative interventions in our review. Broader studies incorporating
      different contexts may help support funding for local authority-sponsored public
      health initiatives.

PMID- 29462345
TI  - Dynamics of metabolic responses to periods of combined heat and drought in
      Arabidopsis thaliana under ambient and elevated atmospheric CO2.
AB  - As a consequence of global change processes, plants will increasingly be
      challenged by extreme climatic events, against a background of elevated
      atmospheric CO2. We analysed responses of Arabidopsis thaliana to periods of a
      combination of elevated heat and water deficit at ambient and elevated CO2 in
      order to gain mechanistic insights regarding changes in primary metabolism.
      Metabolic changes induced by extremes of climate are dynamic and specific to
      different classes of molecules. Concentrations of soluble sugars and amino acids
      increased transiently after short (4-d) exposure to heat and drought, and
      readjusted to control levels under prolonged (8-d) stress. In contrast, fatty
      acids showed persistent changes during the stress period. Elevated CO2 reduced
      the impact of stress on sugar and amino acid metabolism, but not on fatty acids.
      Integrating metabolite data with transcriptome results revealed that some of the
      metabolic changes were regulated at the transcriptional level. Multivariate
      analyses grouped metabolites on the basis of stress exposure time, indicating
      specificity in metabolic responses to short and prolonged stress. Taken together,
      the results indicate that dynamic metabolic reprograming plays an important role
      in plant acclimation to climatic extremes. The extent of such metabolic
      adjustments is less under high CO2, further pointing towards the role of high CO2
      in stress mitigation.

PMID- 29462347
TI  - Long-term quality-of-care score predicts incident chronic kidney disease in
      patients with type 2 diabetes.
AB  - Background: Chronic kidney disease (CKD) is a common complication of diabetes,
      and requires long-term medical care. However, besides the blood glucose level, no
      reliable method is currently available to link the quality of care and the
      development of CKD. We therefore developed a long-term quality-of-care score for
      predicting the occurrence of CKD in patients with type 2 diabetes. Methods: In
      this retrospective cohort study, using Taiwan's Longitudinal Cohort of Diabetes
      Patients Database and the medical records in a medical center, we identified
      incident patients with type 2 diabetes during 1999-2003 and followed them until
      2011. A quality-of-care score (from 0 to 8) was calculated according to process
      indicators (frequencies of HbA1c and lipid profile testing and urine, foot, and
      retinal examinations), intermediate outcome indicators (low-density lipoprotein,
      blood pressure, and HbA1c) and comorbidity of hypertension. We used Cox
      regression models to evaluate the association between the score and the incidence
      of CKD. Results: Of the 4754 patients enrolled, 1407 developed CKD after a mean
      follow-up of 9.06 years. Compared with the risk of developing a CKD event in
      patients with scores <=2, the risk was 69% lower in those with quality-of-care
      scores >=5 (hazard ratio [HR] 0.31; 95% confidence interval [CI] 0.25-0.40) and
      33% lower in those with scores between 3 and 4 (HR 0.67; 95% CI 0.59-0.77).
      Conclusions: Good quality of care can reduce the risk of CKD in patients with
      type 2 diabetes. The score developed in this study had a significant association
      with the risk of CKD and thus can be applied to guide the care for these
      patients.

PMID- 29462348
TI  - Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal
      anti-neutrophil cytoplasm antibody-associated vasculitis.
AB  - Background: Current guidelines advise that rituximab or cyclophosphamide should
      be used for the treatment of organ-threatening disease in anti-neutrophil
      cytoplasm antibody (ANCA)-associated vasculitis (AAV), although few studies have
      examined the efficacy and safety of these agents in combination. Methods: We
      conducted a single-centre cohort study of 66 patients treated with a combination
      of oral corticosteroids, rituximab and low-dose pulsed intravenous
      cyclophosphamide followed by a maintenance regimen of azathioprine and tapered
      steroid for the treatment of biopsy-proven renal involvement in AAV. Patients
      were followed for a median of 56 months. Case-control analysis with 198
      propensity-matched cases from European Vasculitis Study Group (EUVAS) trials
      compared long-term differences in relapse-free, renal and patient survival.
      Results: At entry, the median Birmingham Vasculitis Activity Score (BVAS) was 19
      and estimated glomerular filtration rate was 25 mL/min. Cumulative doses of
      rituximab, cyclophosphamide and corticosteroids were 2, 3 and 4.2 g,
      respectively, at 6 months. A total of 94% of patients achieved disease remission
      by 6 months (BVAS < 0) and patient and renal survival were 84 and 95%,
      respectively, at 5 years. A total of 84% achieved ANCA-negative status and 57%
      remained B cell deplete at 2 years, which was associated with low rates of major
      relapse (15% at 5 years). The serious infection rate during long-term follow-up
      was 1.24 per 10 patient-years. Treatment with this regimen was associated with a
      reduced risk of death {hazard ratio [HR] 0.29 [95% confidence interval (CI) 0.125
      0.675], P = 0.004}, progression to end-stage renal disease (ESRD) [HR 0.20 (95%
      CI 0.06-0.65), P = 0.007] and relapse [HR 0.49 (95% CI 0.25-0.97), P = 0.04]
      compared with propensity-matched patients enrolled in EUVAS trials. Conclusions:
      This regimen is potentially superior to current standards of care, and controlled
      studies are warranted to establish the utility of combination drug approaches in
      the treatment of AAV.

PMID- 29462349
TI  - Jumonji domain-containing protein family: the functions beyond lysine
      demethylation.

PMID- 29462350
TI  - The relationship between alcohol use and long-term cognitive decline in middle
      and late life: a longitudinal analysis using UK Biobank.

PMID- 29462351
TI  - One-on-one care management and procurement of Naloxone for ambulatory use.
AB  - Background: Morbidity and mortality from prescription opioids has reached
      unprecedented levels. Opioids remain part of chronic pain treatment in primary
      care. This study was designed to determine whether one-on-one care management
      increases procurement of Naloxone, an opioid antagonist shown to reduce morbidity
      and mortality in opioid overdoses. Methods: Participants included all patients
      >=18 years enrolled in a primary care-based chronic pain management program and
      who were prescribed a daily dose of opioids for treatment of chronic pain. In
      total, 153 patients chose to participate. Each had a 1 h one-on-one education
      meeting with a registered nurse. Results: Among the enrolled, eight patients
      (5.2%) had procured Naloxone prior to intervention. Overall, 31 additional
      patients (20.2%) procured Naloxone after intervention, a 288% relative
      improvement in the attainment of Naloxone (P < 0.0001) (chi2 = 29.032 with 1
      degree freedom). Of the 114 participants who never procured Naloxone, 69.3%
      believed it was unnecessary, 20% forgot about Naloxone, 8% said it was cost
      prohibitive, 3.5% had access concerns and 0.9% had concerns about side effects.
      Conclusion: Direct one-on-one nurse care management sessions were associated with
      an increased procurement of Naloxone in a primary care-based pain management
      program. A significant number of patients believed Naloxone was unnecessary after
      the intervention.

PMID- 29462352
TI  - Inhibition of corticosterone synthesis and its effect on acute phase proteins,
      heat shock protein 70, and interleukin-6 in broiler chickens subjected to feed
      restriction.
AB  - The aim of the current study was to elucidate whether inhibition of
      corticosterone (CORT) synthesis could modify stress response to feed deprivation
      and its possible interactions with feed restriction in the neonatal period in
      broiler chickens. Equal numbers of broiler chicks were subjected to either 60%
      feed restriction (60FR) or ad libitum (AL) on d 4, 5, and 6. On day 7, blood
      CORT, acute phase proteins (APP), interleukin-6 (IL-6) levels, and brain heat
      shock protein 70 (HSP70) expression were determined. On d 35, chickens in each
      early age feeding regimen were subjected to one of the following treatments: (i)
      ad libitum feeding (ALF), (ii) 24 h feed deprivation (SFR), or (iii) 24 h feed
      deprivation with intramuscular injection of 1,1-bis(4-chlorophenyl)-2,2,2
      trichloroethane (DDT) at 100 mg/kg BW (SFR+DDT). The effect of SFR on CORT, APP,
      IL-6, and HSP 70 were determined on d 36. The results showed that subjecting
      chicks to 60FR significantly elevated CORT and brain HSP70 concentration compared
      to the AL group on d 7. The early feeding regimen had no significant effect on
      CORT, alpha-1 acid glycoprotein (AGP), ovotransferrin (OVT), ceruoplasmin (CP),
      IL-6, or brain HSP70 on d 36. The CORT, AGP, OVT, CP, IL-6, and brain HSP70
      expression of SFR birds following 24 h of feed deprivation (d 36) were
      significantly higher than their ALF and SFR+DDT counterparts. Both ALF and
      SFR+DDT birds had similar values. Stress attributed to feed deprivation without
      concurrent increase in CORT had a negligible effect on serum levels of APP and IL
      6 and brain HSP70 expression.

PMID- 29462353
TI  - Predicition models for delayed graft function: external validation on The Dutch
      Prospective Renal Transplantation Registry.
AB  - Background: Delayed graft function (DGF) is a common complication after kidney
      transplantation in the era of accepting an equal number of brain- and circulatory
      death donor kidneys in the Netherlands. To identify those cases with an increased
      risk of developing DGF, various multivariable algorithms have been proposed. The
      objective was to validate the reproducibility of four predictive algorithms by
      Irish et al. (A risk prediction model for delayed graft function in the current
      era of deceased donor renal transplantation. Am J Transplant 2010;10:2279-2286)
      (USA), Jeldres et al. (Prediction of delayed graft function after renal
      transplantation. Can Urol Assoc J 2009;3:377-382) (Canada), Chapal et al. (A
      useful scoring system for the prediction and management of delayed graft function
      following kidney transplantation from cadaveric donors. Kidney Int 2014;86:1130
      1139) (France) and Zaza et al. (Predictive model for delayed graft function based
      on easily available pre-renal transplant variables. Intern Emerg Med 2015;10:135
      141) (Italy) according to a novel framework for external validation. Methods: We
      conducted a prospective observational study with data from the Dutch Organ
      Transplantation Registry (NOTR). Renal transplant recipients from all eight Dutch
      academic medical centers between 2002 and 2012 who received a deceased allograft
      were included (N = 3333). The four prediction algorithms were reconstructed from
      donor, recipient and transplantation data. Their predictive value for DGF was
      validated by c-statistics, calibration statistics and net benefit analysis. Case
      mix (un)relatedness was investigated with a membership model and mean and
      standard deviation of the linear predictor. Results: The prevalence of DGF was
      37%. Despite a significantly different case-mix, the US algorithm by Irish was
      best reproducible, with a c-index of 0.761 (range 0.756 - 0.762), and well
      calibrated over the complete range of predicted probabilities of having DGF. The
      US model had a net benefit of 0.242 at a threshold probability of 0.25, compared
      with 0.089 net benefit for the same threshold in the original study, equivalent
      to correctly identifying DGF in 24 cases per 100 patients (true positive results)
      without an increase in the number of false-positive results. Conclusions: The US
      model by Irish et al. was generalizable and best transportable to Dutch
      recipients with a deceased donor kidney. The algorithm detects an increased risk
      of DGF after allocation and enables us to improve individual patient management.

PMID- 29462354
TI  - Microdam Impoundments Provide Suitable Habitat for Larvae of Malaria Vectors: An
      Observational Study in Western Kenya.
AB  - Impoundments formed by microdams in rural areas of Africa are important sources
      of water for people, but they provide potential larval habitats for Anopheles
      (Diptera: Culicidae) mosquitoes that are vectors of malaria. To study this
      association, the perimeters of 31 microdam impoundments in western Kenya were
      sampled for Anopheles larvae in three zones (patches of floating and emergent
      vegetation, shorelines of open water, and aggregations of cattle hoofprints)
      across dry and rainy seasons. Of 3,169 larvae collected, most (86.8%) were
      collected in the rainy season. Of 2,403 larvae successfully reared to fourth
      instar or adult, nine species were identified; most (80.2%) were Anopheles
      arabiensis Patton, sampled from hoofprint zones in the rainy season. Other
      species collected were Anopheles coustani Laveran, Anopheles gambiae s.s. Giles,
      Anopheles funestus Giles, and Anopheles rivulorum Leeson, Anopheles pharoensis
      Theobald, Anopheles squamosus Theobald, Anopheles rufipes (Gough), and Anopheles
      ardensis (Theobald). Larvae of An. funestus were uncommon (1.5%) in both dry and
      rainy seasons and were confined to vegetated zones, suggesting that microdam
      impoundments are not primary habitats for this important vector species, although
      microdams may provide a dry season refuge habitat for malaria vectors,
      contributing to population persistence through the dry season. In this study,
      microdam impoundments clearly provided habitat for the malaria vector An.
      arabiensis in the rainy season, most of which was within the shallow apron side
      of the impoundments where people brought cattle for watering, resulting in
      compacted soil with aggregations of water-filled hoofprints. This observation
      suggests a potential conflict between public health concerns about malaria and
      people's need for stable and reliable sources of water.

PMID- 29462355
TI  - Small molecule modulator of protein disulfide isomerase attenuates mutant
      huntingtin toxicity and inhibits endoplasmic reticulum stress in a mouse model of
      Huntington's disease.
AB  - Huntington's disease (HD) is caused by a cytosine-adenine-guanine (CAG)
      trinucleotide repeat expansion in the huntingtin (HTT) gene encoding an elongated
      polyglutamine tract within the N-terminal of the huntingtin protein (Htt) and
      leads to Htt misfolding, aberrant protein aggregation, and progressive appearance
      of disease symptoms. Chronic activation of endoplasmic reticulum (ER) stress by
      mutant Htt (mHtt) results in cellular dysfunction and ultimately cell death.
      Protein disulfide isomerase (PDI) is a chaperone protein located in the ER. Our
      previous studies demonstrated that mHtt caused PDI to accumulate at mitochondria
      associated ER membranes and triggered cell death, and that modulating PDI
      activity using small molecules protected cells again mHtt toxicity in cell and
      brain slice models of HD. In this study, we demonstrated that PDI is upregulated
      in the HD human brain, in cell and mouse models. Chronic administration of a
      reversible, brain penetrable small molecule PDI modulator, LOC14 (20 mg/kg/day),
      significantly improved motor function, attenuated brain atrophy and extended
      survival in the N171-82Q HD mice. Moreover, LOC14 preserved medium spiny neuronal
      marker dopamine- and cyclic-AMP-regulated phosphoprotein of molecular weight 32
      000 (DARPP32) levels in the striatum of HD mice. Mechanistic study revealed that
      LOC14 suppressed mHtt-induced ER stress, indicated by repressing the abnormally
      upregulated ER stress proteins in HD models. These findings suggest that LOC14 is
      promising to be further optimized for clinical trials of HD, and modulation of
      signaling pathways coping with ER stress may constitute an attractive approach to
      reduce mHtt toxicity and identify new therapeutic targets for treatment of HD.

PMID- 29462356
TI  - Nutrient Fortification of Human Donor Milk Affects Intestinal Function and
      Protein Metabolism in Preterm Pigs.
AB  - Background: Nutrient fortification of human milk is often required to secure
      adequate growth and organ development for very preterm infants. There is concern
      that formula-based fortifiers (FFs) induce intestinal dysfunction, feeding
      intolerance, and necrotizing enterocolitis (NEC). Bovine colostrum (BC) may be an
      alternative nutrient fortifier, considering its high content of protein and milk
      bioactive factors. Objective: We investigated whether BC was superior to an FF
      product based on processed bovine milk and vegetable oil to fortify donor human
      milk (DHM) for preterm pigs, used as a model for infants. Methods: Sixty preterm
      pigs from 4 sows (Danish Landrace * Large White * Duroc, birth weight 944 +/- 29
      g) received decreasing volumes of parenteral nutrition (96-72 mL ? kg-1 ? d-1)
      and increasing volumes of enteral nutrition (24-132 mL ? kg-1 ? d-1) for 8 d.
      Pigs were fed donor porcine milk (DPM) and DHM with or without FF or BC
      fortification (+4.6 g protein ? kg-1 ? d-1). Results: DPM-fed pigs showed higher
      growth (10-fold), protein synthesis (+15-30%), villus heights, lactase and
      peptidase activities (+30%), and reduced intestinal cytokines (-50%) relative to
      DHM pigs (all P < 0.05). Fortification increased protein synthesis (+20-30%), but
      with higher weight gain and lower urea and cortisol concentrations for DHM+BC
      compared with DHM+FF pigs (2- to 3-fold differences, all P <= 0.06). DHM+FF pigs
      showed more diarrhea and reduced lactase and peptidase activities, hexose uptake,
      and villus heights relative to DHM+BC or DHM pigs (30-90% differences, P < 0.05).
      Fortification did not affect NEC incidence but DHM+BC pigs had lower colonic
      interleukin (IL)-6 and IL-8 concentrations relative to the remaining pigs (-30%,
      P = 0.06). DHM+FF pigs had higher stomach bacterial load than did DHM, and higher
      bacterial density along intestinal villi than did DHM and DHM+BC pigs (2- to 3
      fold, P < 0.05). Conclusions: The FF product investigated in this study reduced
      growth, intestinal function, and protein utilization in DHM-fed preterm pigs,
      relative to BC as fortifier. The relevance of BC as an alternative nutrient
      fortifier for preterm infants should be tested.

PMID- 29462358
TI  - Erratum.

PMID- 29462357
TI  - NICE public health guidance update.

PMID- 29462359
TI  - Privatization in the Irish hospital sector since 1980.
AB  - Background: Privatization has transformed health care systems over the last
      several decades. This article examines trends in bed supply in Ireland between
      1980 and 2015 within the context of government policy on bed provision in a
      system of inequitable access to care. Ireland has not published bed data on
      private hospitals since the 1980s, even if they comprise about one-quarter of all
      hospitals. However, this article presents, for the first time, annual bed data
      since the 1980s collected from private hospitals and used to trace the evolution
      of bed supply over time. Methods: Bed data were collected for private Irish
      hospitals for the years 1980-2015, mainly through direct requests to hospitals.
      Additional sources included the Irish Medical Directory, private health insurance
      data, hospital company records and newspaper archives. Results: Subject to data
      caveats explained in the article, between 1980 and 2015, total inpatient beds
      decreased by 25.5% nationally. Inpatient bed numbers in private for-profit (PFP)
      hospitals rose from 0 to 1075 but decreased from 9601 to 5216 in private not-for
      profit (PNFP) hospitals and from 7028 to 6092 in public hospitals (using the
      Irish hospital classification, beds in private hospitals increased from 1518 to
      1910 but decreased from 15 111 to 10 473 in public hospitals). Also, by 2015,
      24.1% of PFP hospital beds were day beds, compared to 17.7% for PNFP and 15.7%
      for public hospitals (using the Irish classification, by 2015, day beds accounted
      for 23.8% of beds in private hospitals and 16.1% in public hospitals).
      Conclusions: Trends in bed supply in Ireland between 1980 and 2015 are documented
      empirically for all Irish acute hospitals and contextualized within government
      policy on bed provision. The Irish acute hospital system has experienced
      privatization reforms supported by the government over the last several decades.

PMID- 29462360
TI  - Effects of fatty acid glyceride product SILOhealth 104 on the growth performance
      and carcass composition of broiler chickens.
AB  - Butyric acid is the primary energy source for colonocytes, and has shown
      potential as an alternative to in-feed antibiotics, due to its antimicrobial
      activity and positive effects on production performance traits of broiler
      chickens. SILOhealth 104 (SILO S.P.A., Florence, Italy) is a commercial product
      mainly containing mono- and di-glycerides of butyrate with a small portion of
      propionic, caprylic, capric, and lauric acid mono- and di-glycerides. Its effects
      on broiler performance and carcass composition have yet to be evaluated. Four
      hundred-eighty day-old male Ross 308 birds were divided into different dietary
      treatment groups with equal starting weights and fed a diet containing 0, 500,
      1,000, 2,000, or 3,000 ppm of SILOhealth 104 for 35 days. There were no
      significant differences in overall average daily gain or feed: gain ratio with
      the addition of SILOhealth 104 to the diets (P > 0.05). At 5 wk of age, abdominal
      fat weight was reduced in birds supplemented with SILOhealth 104 in a dose
      responsive manner (P < 0.05), while breast muscle weight increased with
      supplementation, with significant increases in 2,000 ppm and 3,000 ppm birds
      compared to controls (P < 0.05). A significant reduction in gene expression of
      both forkhead box protein O4 and myostatin, 2 factors that can inhibit protein
      synthesis, was found in the breast muscle of all SILOhealth 104 treated birds (P
      < 0.05). In addition, gene expression in the adipose tissue, including acetyl-CoA
      carboxylase alpha and lipoprotein lipase, which are associated with lipid
      metabolism, was significantly decreased and increased, respectively, by the
      supplementation of SILOhealth 104 (P < 0.05). These data suggest that the
      components of SILOhealth 104 can positively affect the deposition of muscle,
      while reducing abdominal fat deposition in broiler chickens.

PMID- 29462361
TI  - Wet feed and cold water as heat stress modulators in growing Muscovy ducklings.
AB  - In an attempt to alleviate the deleterious effects of high summer temperatures,
      the present study investigated the effects of wet feed and cold water on the
      growth performance, carcass and meat quality, leg problems, physiological
      responses, and blood parameters of growing Muscovy ducklings. A total of 180 4
      week-old ducklings was randomly divided into 6 experimental groups in a 3 * 2
      factorial design that included 3 feed systems (AD: ad libitum dry; DW: diurnal
      wet; and AW: ad libitum wet) and 2 systems of water (TW: tap water; and CW: cold
      water). Access to wet feed and cold water affected the growth performance,
      dressed carcass, gizzard, meat quality (tenderness, juiciness, and
      susceptibility), tonic immobility, body temperature, and blood parameters
      [albumin: globulin (A: G) ratio and levels of glucose, alanine transferase (ALT),
      total antioxidant capacity (T-AOC), and malondialdehyde (MDA)] of the ducklings
      but had no significant effect on plumage condition, shank length, keel bone
      length, leg problems, or breast blisters. The body weight (BW) of the DW group
      was 1.97 and 3.12% greater than that of the AD and AW groups, respectively, and
      the BWG of the DW group was 6.91 and 10.72% greater than that of the AD and AW
      groups, respectively. Therefore, providing access to wet feed and cold water is
      highly recommended when raising Muscovy ducks in open houses under high
      temperature conditions.

PMID- 29462362
TI  - Postoperative Delirium in Glioblastoma Patients: Risk Factors and Prognostic
      Implications.
AB  - BACKGROUND: Delirium is a postoperative neurological morbidity in glioblastoma
      whose risk factors, incidence, and prognostic implications remain undefined.
      OBJECTIVE: To develop an algorithm using preoperative factors to predict
      postoperative delirium. METHODS: Retrospective analysis of 554 consecutive
      patients (mean age = 61.5 yr; 42% female) undergoing first glioblastoma procedure
      at our institution 2005 to 2011. RESULTS: Postoperative delirium occurred in 7%
      of patients (n = 38). Patients undergoing biopsy (10%; n = 54) did not experience
      delirium. In patients undergoing resection (n = 500), multivariate logistic
      regression identified 5 factors independently predicting postoperative delirium:
      age, chronic pulmonary disease, psychiatric history, bihemispheric tumors, and
      tumor size. We developed a score function entitled "GRAD" (Glioblastoma Risk
      Assessment for Delirium) to stratify patients into risk categories by assigning
      point(s) to each preoperative factor based on the relative magnitude of its
      regression coefficient. Point totals were summed for each patient: patients with
      0 to 2 (n = 227) and 3 to 7 (n = 221) points were designated as low and high risk
      with postoperative delirium rates of 2% vs 15%, respectively (chi-square; P <
      .001), with the model validated using a separate patient cohort. Postoperative
      delirium lengthened hospital stays (P < .001), decreased likelihood of discharge
      home (P < .001), and was independently associated with decreased survival (4.5 vs
      13.4 mo; hazard ratio = 1.9 [1.2-2.8]) in multivariate analysis. CONCLUSION: We
      developed a model to predict development of postoperative delirium using 2 tumor
      specific (bihemispheric tumors and tumor size) and 3 patient-specific (age,
      psychiatric history, and chronic pulmonary disease) factors. High-risk patients
      and their families should be counseled preoperatively, and this risk could be
      considered in the choice of biopsy vs resection, and resection patients should be
      monitored closely postoperatively.

PMID- 29462363
TI  - A Gene Regulatory Network for Cellular Reprogramming in Plant Regeneration.
AB  - Wounding triggers organ regeneration in many plant species, and application of
      plant hormones, such as auxin and cytokinin, enhances their regenerative
      capacities in tissue culture. Recent studies have identified several key players
      mediating wound- and/or plant hormone-induced cellular reprogramming, but the
      global architecture of gene regulatory relationships underlying plant cellular
      reprogramming is still far from clear. In this study, we uncovered a gene
      regulatory network (GRN) associated with plant cellular reprogramming by using an
      enhanced yeast one-hybrid (eY1H) screen systematically to identify regulatory
      relationships between 252 transcription factors (TFs) and 48 promoters. Our
      network analyses suggest that wound- and/or hormone-invoked signals exhibit
      extensive cross-talk and regulate many common reprogramming-associated genes via
      multilayered regulatory cascades. Our data suggest that PLETHORA 3 (PLT3),
      ENHANCER OF SHOOT REGENERATION 1 (ESR1) and HEAT SHOCK FACTOR B 1 (HSFB1) act as
      critical nodes that have many overlapping targets and potentially connect
      upstream stimuli to downstream developmental decisions. Interestingly, a set of
      wound-inducible APETALA 2/ETHYLENE RESPONSE FACTORs (AP2/ERFs) appear to regulate
      these key genes, which, in turn, form feed-forward cascades that control
      downstream targets associated with callus formation and organ regeneration. In
      addition, we found another regulatory pathway, mediated by LATERAL ORGAN
      BOUNDARY/ASYMMETRIC LEAVES 2 (LOB/AS2) TFs, which probably plays a distinct but
      partially overlapping role alongside the AP2/ERFs in the putative gene regulatory
      cascades. Taken together, our findings provide the first global picture of the
      GRN governing plant cell reprogramming, which will serve as a valuable resource
      for future studies.

PMID- 29462364
TI  - Bioavailability and Pharmacokinetics of Oral Cocaine in Humans.
AB  - The pharmacokinetic profile of oral cocaine has not been fully characterized and
      prospective data on oral bioavailability are limited. A within-subject study was
      performed to characterize the bioavailability and pharmacokinetics of oral
      cocaine. Fourteen healthy inpatient participants (six males) with current
      histories of cocaine use were administered two oral doses (100 and 200 mg) and
      one intravenous (IV) dose (40 mg) of cocaine during three separate dosing
      sessions. Plasma samples were collected for up to 24 h after dosing and analyzed
      for cocaine and metabolites by gas chromatography-mass spectrometry.
      Pharmacokinetic parameters were calculated by non-compartmental analysis, and a
      two-factor model was used to assess for dose and sex differences. The mean +/-
      SEM oral cocaine bioavailability was 0.32 +/- 0.04 after 100 and 0.45 +/- 0.06
      after 200 mg oral cocaine. Volume of distribution (Vd) and clearance (CL) were
      both greatest after 100 mg oral (Vd = 4.2 L/kg; CL = 116.2 mL/[min kg]) compared
      to 200 mg oral (Vd = 2.9 L/kg; CL = 87.5 mL/[min kg]) and 40 mg IV (Vd = 1.3
      L/kg; CL = 32.7 mL/[min kg]). Oral cocaine area-under-thecurve (AUC) and peak
      concentration increased in a dose-related manner. AUC metabolite-to-parent ratios
      of benzoylecgonine and ecgonine methyl ester were significantly higher after oral
      compared to IV administration and highest after the lower oral dose. In addition,
      minor metabolites were detected in higher concentrations after oral compared to
      IV cocaine. Oral cocaine produced a pharmacokinetic profile different from IV
      cocaine, which appears as a rightward and downward shift in the concentration
      time profile. Cocaine bioavailability values were similar to previous estimates.
      Oral cocaine also produced a unique metabolic profile, with greater
      concentrations of major and minor metabolites.

PMID- 29462365
TI  - Supratentorial Cavernous Malformations Involving the Corticospinal Tract and
      Sensory Motor Cortex: Treatment Strategies, Surgical Considerations, and
      Outcomes.
AB  - BACKGROUND: Cavernous malformations (CMs) are congenital malformations and may be
      located anywhere in the brain. We present a series of CMs located close to or
      inside of the motor-sensory cortex or corticospinal tract (CST) with clinical
      onset due to hemorrhage or mass effect. In such cases, surgery becomes an
      acceptable option. OBJECTIVE: To evaluate the role of diffusion tensor imaging
      (DTI), functional-magnetic-resonance imaging (fMRI), intraoperative
      neurophysiological monitoring, neuronavigation, and brain-mapping and the
      clinical results of surgical treatment of CMs in this critical location. METHODS:
      The study included 54 patients harboring 22 cortical and 32 deep locations. This
      series was distinct because in group I, where the DTI was not obtained, and in
      the group II, where this evaluation was performed. RESULTS: The postoperative
      permanent morbidity rate was 4% in the historical group for the deeper CMs, and
      there was no morbidity in the second group. DTI and fMRI permitted us to estimate
      the distance between the CMs and both the cortical activation cluster and the
      pyramidal tract. These data, in addition to intraoperative mapping and
      monitoring, made it necessary for us to perform a partial resection in 2 cases in
      the second series. CONCLUSION: CMs are congenital lesions and CST fibers can run
      directly on their surface. Integration of fMRI and DTI data with intraoperative
      functional monitoring and direct cortical and subcortical mapping are mandatory
      to accomplish an optimal resection, tailoring the best surgical approach to the
      acceptable morbidity. A subtotal resection could be considered an option for deep
      locations.

PMID- 29462366
TI  - PHYSICAL CHARACTERISATION OF FOUR DIFFERENT COMMERCIAL DIGITAL BREAST
      TOMOSYNTHESIS SYSTEMS.
AB  - The aim of this article was to characterise the performance of four different
      digital breast tomosynthesis (DBT) systems in terms of dose and image quality
      parameters. One of them, GE Pristina, has never been tested before. Average
      glandular doses were measured both in DBT and 2D full field digital mammography
      mode. Several phantoms were employed to perform signal difference to noise ratio,
      slice sensitivity profile, slice to slice incrementation, chest wall offset, z
      axis geometry, artefact spread function, low contrast detectability, contrast
      detail evaluations, image uniformity and in-plane MTF in chest wall-nipple and in
      tube-travel directions. There are many differences in DBT systems explored: the
      angular range, detector type, reconstruction algorithms, and the presence or not
      of the grid. Even if it is not simple to calculate a global figure of merit, the
      analysis of all the collected data can be useful in a contest of a quality
      assurance program to define a set of values that could be used as benchmarks.

PMID- 29462367
TI  - Expression of angiogenic factors and plexiform lesions in the lungs of broiler
      and layer chickens: A comparison.
AB  - Plexiform lesions are characteristic histological changes of pulmonary arteries
      in human patients with severe pulmonary arterial hypertension (PAH) and are
      regarded as angiogenic lesions. Meat-type broiler chickens are susceptible to PAH
      and can develop plexiform lesions spontaneously. Whether the lesion development
      in broilers is associated with PAH predisposition and lung angiogenic environment
      remains unclear. Moreover, little is known about the cellular origin of these
      structures. In this work, plexiform lesions were detected in both layer chickens
      (a strain known to be resistant to PAH) and broiler chickens aged between 1 and 6
      wk with normal pulmonary arterial pressures. Within each of the sampled ages, the
      lesion density did not differ between strains, with an exception of wk 4 when
      broiler was higher than layer. In contrast to the trend of age-related decline in
      layers, lesion densities in broilers demonstrated bi-phasic alterations
      characterized by a gradual decrease during wk 1 to 3 followed by a sudden
      increase at wk 4. The mRNA of 6 angiogenic factors in the lung tissue, namely,
      vascular endothelial growth factor receptor (VEGFR)-2, angiopoietin (Ang)-1,
      angiopoietin receptor Tie-2, transforming growth factor (TGF)-beta1, hepatocyte
      growth factor (HGF), and interleukin (IL)-8, were differentially expressed
      between strains. However, none of them was found to be significantly correlated
      with the lesion density by strain and age-adjusted partial correlation analysis.
      An in vivo experiment revealed impaired differentiation of endothelial progenitor
      cells (EPC) into endothelial cells during the producing of plexiform lesions, as
      evidenced by increased expression of endothelial CD133, a maker of EPC, but
      reduced expression of CD31, a marker of mature endothelial cells, in the parent
      vessels of plexiform lesions compared to normal vessels. Collectively, it appears
      unlikely that the predisposition to PAH or intrapulmonary angiogenic environment
      contributes to the lesion development in broilers when compared with layers. It
      is suggested that the lesion development is associated with increased pulmonary
      arterial pressure, and that local EPC dysfunction may play a role in the process.

PMID- 29462368
TI  - Dural Cells Release Factors Which Promote Cancer Cell Malignancy and Induce
      Immunosuppressive Markers in Bone Marrow Myeloid Cells.
AB  - BACKGROUND: Thirty per cent of cancer patients develop spine metastases with a
      substantial number leading to spinal cord compression and neurological deficits.
      Many demonstrate a propensity toward metastasis to the posterior third of the
      vertebral body. The dura, the outer layer of the meninges, lies in intimate
      contact with the posterior border of the vertebral body and has been shown to
      influence adjacent bone. The effects of the dura on bone marrow and cancer cells
      have not been examined. Understanding the biology of spinal metastasis will
      provide insights into mechanisms of cancer growth and allow for new treatment
      strategies. OBJECTIVE: To examine the extent to which dura influences bone
      marrow/tumor cell metastatic characteristics. METHODS: Dura conditioned media
      (DCM) from primary dura was examined for the ability to stimulate tumor cell
      proliferation/invasion and to alter bone marrow cell populations. RNA sequencing
      of dural fibroblasts was performed to examine expression of cytokines and growth
      factors. RESULTS: DCM induced a significant increase in invasion and
      proliferation of multiple tumor cell lines, and of patient-derived primary spinal
      metastatic cells. DCM also increased the proliferation of bone marrow myeloid
      cells, inducing expression of immunosuppressive markers. RNA sequencing of dural
      fibroblasts demonstrated abundant expression of cytokines and growth factors
      involved in cancer/immune pathways. CONCLUSION: Factors released by primary dural
      cells induce proliferation of tumor cells and alter bone marrow to create a
      fertile environment for tumor growth. The dura therefore may play an important
      role in the increased incidence of metastases to adjacent bone.

PMID- 29462369
TI  - CYP17 gene plays a key role in goose genital growth by influencing the
      testosterone level at puberty.
AB  - All birds reproduce by internal fertilization, but only 3% of birds have external
      genitalia. Hormone secretions and body size influence genital growth, but the
      actual regulatory mechanism is rarely reported. Thus, using 35 geese as
      experimental material, the regulatory mechanism of goose external genitalia
      growth was explored by measuring body size parameters, serum hormone
      concentrations, and related gene expression. In this study, genital growth was
      different among tested geese, but histological and morphological results showed
      that all geese external genitalia contained complete tissues. Measurements of
      hormone levels showed that at puberty, as the genital length increased, irregular
      decreases were observed in the levels of follicle-stimulating hormone (FSH) and
      luteinizing hormone (LH), whereas an irregular increase was observed in the
      levels of testosterone (T); furthermore, the levels of testosterone (T) gradually
      increased to a peak at 34 weeks. Based on RT-PCR results, as the genital length
      increased, only the expression of 17alpha-hydroxylase/17, 20-lyase (CYP17) mRNA
      slightly decreased at first, and then significantly increased to a peak, whereas
      the expression patterns of other genes were irregular. Furthermore, the CYP17
      immunohistochemistry results also showed a pattern that was highly consistent
      with the patterns of mRNA expression and T secretion. In addition, based on body
      measurements, as body weight increased, the genital length increased. Thus, these
      results suggested that the CYP17 gene plays a key role in goose genital growth.

PMID- 29462370
TI  - The effect of Eimeria maxima infection on the expression of amino acid and sugar
      transporters aminopeptidase, as well as the di- and tri-peptide transporter
      PepT1, is not solely due to decreased feed intake.
AB  - Coccidiosis caused by Eimeria in poultry is endemic to poultry operations and
      results in decreased feed intake, diarrhea, and decreased weight gain. The goal
      was to determine the effect of Eimeria maxima infection on the expression of
      genes that encode peptide and amino acid transporters (AATs), and also to
      determine whether decreased feed intake contributes to the change in gene
      expression by including a pair-fed group of broilers. Three groups of male Ross
      broilers: 1) not infected, 2) infected, and 3) not infected pair-fed groups were
      used. Chicks were infected with 1,000 oocysts of E. maxima at 21 d of age. Feed
      consumption was obtained daily, and at d 0, 3, 5, 7, 10, and 14 post-infection
      (PI), 6 birds were euthanized, and a portion of the jejunum was removed for qRT
      PCR. Infected birds had significantly decreased feed consumption between d 6 to 9
      PI. At d 7 PI infected birds had a 45% reduction in weight gain, and pair-fed
      birds had a 32% reduction in weight gain. The feed conversion ratio at d 7 PI of
      infected birds was 2.2 while that of pair-fed birds was 1.7, compared to 1.5 in
      uninfected birds. Growth parameters were more affected in infected birds than in
      pair-fed birds. By measuring expression levels of nutrient uptake and processing
      genes via qRT-PCR, it was determined that genes encoding proteins located at the
      brush border of the gut epithelium were affected by infection as well as change
      in feed intake. The expression of AATs B degrees AT, b degrees ,+AT, EAAT3, and
      PepT1 in infected birds decreased sharply at the height of infection; however, in
      birds that were pair fed, an increase in expression of b degrees ,+AT, and PepT1
      was observed, and little change was seen in expression of B degrees AT and EAAT3.
      In summary, the changes in expression of digestive enzymes and nutrient
      transporters are distinct between coccidia-infected birds compared to healthy
      pair-fed birds.

PMID- 29462371
TI  - Ultrastructural diversity between centrioles of eukaryotes.
AB  - Several decades of centriole research have revealed the beautiful symmetry
      present in these microtubule-based organelles, which are required to form
      centrosomes, cilia and flagella in many eukaryotes. Centriole architecture is
      largely conserved across most organisms; however, individual centriolar features
      such as the central cartwheel or microtubule walls exhibit considerable
      variability when examined with finer resolution. In this paper, we review the
      ultrastructural characteristics of centrioles in commonly studied organisms,
      highlighting the subtle and not-so-subtle differences between specific structural
      components of these centrioles. In addition, we survey some non-canonical
      centriole structures that have been discovered in various species, from the
      coaxial bicentrioles of protists and lower land plants to the giant irregular
      centrioles of the fungus gnat Sciara. Finally, we speculate on the functional
      significance of these differences between centrioles, and the contribution of
      individual structural elements such as the cartwheel or microtubules towards the
      stability of centrioles.

PMID- 29462372
TI  - Moving Second Courses of Radiotherapy Forward: Early Re-Irradiation After
      Surgical Resection for Recurrent Gliomas Improves Efficacy With Excellent
      Tolerability.
AB  - BACKGROUND: Generally, re-irradiation (Re-RT) is offered to patients with glioma
      recurrences with macroscopic lesions. Results are discussed controversially, and
      some centers postulate limited benefit of Re-RT. Re-RT is generally offered to
      tumors up to 4 cm in diameter. Re-resection is also discussed controversially;
      however, recent studies have shown significant benefit. OBJECTIVE: To combine
      proactive re-resection and early Re-RT in patients with recurrent glioma.
      METHODS: We included 108 patients treated between 2002 and 2016 for recurrent
      glioma. All patients underwent surgical resection for recurrence; Re-RT was
      applied with a median dose of 37.5 Gy (range 25 Gy-57Gy/equivalent dose in 2Gy
      fractions [EQD2]) with high-precision techniques. All patients were followed
      prospectively in an interdisciplinary follow-up program. RESULTS: Median follow
      up after Re-RT was 7 mo. Median survival after surgery and Re-RT was 12 mo (range
      1-102 mo). Complete resection had a significant impact on the outcome (P = .03).
      The strongest predictors of outcome were MGMT-promotor methylation and Karnofsky
      Performance Score and time interval between primary and second RT. CONCLUSION:
      Proactive resection of tumor recurrences combined with early Re-RT conveys into
      promising outcome in recurrent glioma. Complete resection and early Re-RT lead to
      improved survival. Thus, moving Re-RT to an earlier timepoint during the
      treatment of recurrent glioma, eg after complete macroscopic removal of the
      tumor, may be crucial for treatment optimization. Using advanced RT techniques,
      side effects are low. Currently, this concept is evaluated in the GLIOCAVE/NOA 17
      trial.

PMID- 29462373
TI  - The Role of Matrix Metalloproteinase-3 in the Doxycycline Attenuation of
      Intracranial Venous Hypertension-Induced Angiogenesis.
AB  - BACKGROUND: The molecular mechanism of brain arteriovenous malformation (BAVM) is
      largely unknown. Intracranial venous hypertension (VH) may enhance focal
      angiogenesis and promote BAVM development and progression. A rat VH model
      effectively simulates the hemodynamic microenvironment of this disease.
      OBJECTIVE: To explore the effect of doxycycline in VH-related angiogenesis, as
      well as the role of matrix metalloproteinase-3 (MMP-3) and other molecular
      factors. METHODS: A rat VH model was generated by common carotid artery and
      distal external jugular vein anastomosis. Microvessel density (MVD) in the
      perisinus area and expression of MMP-3/2/9, VEGF, TIMP-1, TGF-beta, and HIF
      1alpha were examined, with and without daily doxycycline treatment for 4 wk. The
      effects of doxycycline were verified in Vitro using human brain microvascular
      endothelial cells (HBMECs). MMP-3 overexpression or knockdown in HBMECs was used
      to confirm the role of MMP-3 in cell functions. RESULTS: MVD in the perisinus
      cortex was greatly increased after VH. Doxycycline decreased MVD, suppressed MMP
      3 overexpression, and reduced VEGF, TGF-beta, and TIMP-1 levels compared with the
      controls (P < .05). In Vitro, doxycycline decreased HBMEC migration, tube
      formation, and the mRNA, protein, and enzymatic activity levels of MMP-3. MMP-3
      overexpression in HBMECs promoted migration, while knockdown of MMP-3
      significantly attenuated proliferation, migration, and tube formation (P < .05).
      CONCLUSION: Our findings indicate that MMP-3 plays an important role in VH
      related angiogenesis and the promotion of vascular remodeling. Suppression of MMP
      3 overexpression by doxycycline may provide a potential strategy for inhibiting
      BAVM development.

PMID- 29462374
TI  - Surgical Extraction of Cerebral Sparganosis: 2-Dimensional Operative Video.

PMID- 29462375
TI  - Effects of Ginkgo biloba leaves (Ginkgo biloba) and Ginkgo biloba extract on
      nutrient and energy utilization of broilers.
AB  - An experiment using 112 21-day-old male Arbor Acres broilers that were randomly
      allocated to 7 treatments with 8 replicates in a completely randomized design was
      conducted to assess the effects of Ginkgo biloba leaves (Ginkgo biloba, GL) and
      Ginkgo biloba extract (EGB) on utilization of nutrients of broiler chickens. The
      dietary treatments were corn-soybean meal based diets: 1) T1, control diet; 2)
      T2, T1 + 20 g/kg GL; 3) T3, T1 + 40 g/kg GL; 4) T4, T1 + 60 g/kg GL; 5) T5, T1 +
      0.4 g/kg EGB; 6) T6, T1 + 0.8 g/kg EGB; and 7) T7, T1 + 1.2 g/kg EGB. Endogenous
      losses were obtained from another 16 broilers. Excreta samples were collected to
      analyze the dry matter (DM), organic matter (OM), ether extract (EE), crude
      protein (CP), gross energy (GE), and amino acids (AA), and GE was analyzed for
      computation of AME and TME. As compared with those of the control treatment, the
      apparent digestibility (AD) and true digestibility (TD) of EE, CP, Thr, Val, Ile,
      Leu, Phe, Lys, His, and Arg were quadratically (P < 0.05) increased; moreover,
      the AD and TD of Met was linearly (P < 0.05) increased as the concentration of
      the EGB in the diet increased. Increasing GL from 0 to 60 g/kg of diet linearly
      (P < 0.05) increased the AD and TD of EE, Thr, Val, Leu, His, and Met and tended
      (0.05 < P < 0.1) to increase the TME, TMEn, and Arg. Supplementation of EGB
      increased (P < 0.05) AD and TD of EE, Thr, Val, Ile, Leu, Phe, His, and Arg and
      tended (0.05 < P < 0.1) to increase Lys as compared with those in the GL
      supplemented groups. Dietary supplementation of GL and EGB improved the
      utilization of nutrients of broiler chickens in a dose-dependent manner, and the
      optimum supplementation levels of GL or EGB in the diet of broilers was 60 or 0.8
      g/kg of diet, respectively.

PMID- 29462377
TI  - MAGIC Syndrome in a Patient With Crohn's Disease.

PMID- 29462376
TI  - ESTIMATION OF RADIATION EXPOSURE TO THE PATIENTS IN DIAGNOSTIC AND THERAPEUTIC
      INTERVENTIONAL PROCEDURES.
AB  - The present work reports data of the radiation exposure to the patient in various
      diagnostic and therapeutic interventional radiological (IR) procedures. The study
      includes 260 diagnostic and 195 therapeutic exposure data in 455 IR procedures.
      All the IR procedures were performed on a biplane angiographic machine in a
      tertiary care hospital. The radiation exposure was estimated from dose-area
      product (DAP), fluoroscopy time (FT), number of fluoroscopic runs, number of
      images and cumulative dose (CD) value recorded during the procedure. The data
      reported in the present study show significant variability in DAP values in
      diagnostic and therapeutic IR procedures. In diagnostic procedures, the minimum
      median DAP value is 8.93 Gy cm2 for upper limb angiography with mean FT of 2.7
      min and maximum DAP value is 108.8 Gy cm2 for inferior vena cava angiography with
      mean FT of 12.55 min. For therapeutic procedures, the median value of DAP ranges
      from 2.43 Gy cm2 for sclerotherapy with mean FT 0.65 min to 267.23 Gy cm2 for
      coiling of cerebral aneurysm with mean FT of 60.52 min. The DAP value for each
      procedure was also correlated with FT, number of fluoroscopic runs, number of
      images and CD. The reported DAP values in this study are within the range of
      earlier published results which suggest that our finding provides at least
      approximate applicability to other hospitals. The third quartile DAP values of
      the procedures having significant number of patient data (n >= 10) serves as
      provisional reference values for the optimization of procedure protocols.

PMID- 29462378
TI  - Correlating Fecal Calprotectin With Hemoglobin Levels Within 1 Sample.

PMID- 29462379
TI  - A Cross-Talk Between Microbiota-Derived Short-Chain Fatty Acids and the Host
      Mucosal Immune System Regulates Intestinal Homeostasis and Inflammatory Bowel
      Disease.
AB  - Gut microbiota has a fundamental role in the energy homeostasis of the host and
      is essential for proper "education" of the immune system. Intestinal microbial
      communities are able to ferment dietary fiber releasing short-chain fatty acids
      (SCFAs). The SCFAs, particularly butyrate (BT), regulate innate and adaptive
      immune cell generation, trafficing, and function. For example, BT has an anti
      inflammatory effect by inhibiting the recruitment and proinflammatory activity of
      neutrophils, macrophages, dendritic cells, and effector T cells and by increasing
      the number and activity of regulatory T cells. Gut microbial dysbiosis, ie, a
      microbial community imbalance, has been suggested to play a role in the
      development of inflammatory bowel disease (IBD). The relationship between
      dysbiosis and IBD has been difficult to prove, especially in humans, and is
      probably complex and dynamic, rather than one of a simple cause and effect
      relationship. However, IBD patients have dysbiosis with reduced numbers of SCFAs
      producing bacteria and reduced BT concentration that is linked to a marked
      increase in the number of proinflammatory immune cells in the gut mucosa of these
      patients. Thus, microbial dysbiosis and reduced BT concentration may be a factor
      in the emergence and severity of IBD. Understanding the relationship between
      microbial dysbiosis and reduced BT concentration to IBD may lead to novel
      therapeutic interventions.

PMID- 29462380
TI  - Accelerated Infliximab Dosing Increases 30-Day Colectomy in Hospitalized
      Ulcerative Colitis Patients: A Propensity Score Analysis.
AB  - Background: Standard outpatient induction dosing of infliximab (IFX) may not be
      effective in hospitalized ulcerative colitis (UC) patients with higher
      inflammatory burden and colectomy risk. Our aim was to determine whether initial
      IFX induction dose affects 30-day colectomy rate and other disease-related
      outcomes. Methods: IFX-naive hospitalized UC patients receiving at least 1
      inpatient 5 mg/kg (SD) or 10 mg/kg (HD) IFX induction dose were included.
      Baseline demographics and admission-related characteristics were documented.
      Propensity score based matching was used to control for provider bias introduced
      due to nonprotocolized choice of IFX dose. The primary outcome was 30-day
      colectomy; secondary outcomes included the need for an accelerated induction IFX
      (AD), length of stay (LOS), 90-day and 1-year colectomy, and complications.
      Results: Of 146 (120 SD/26 HD) patients included, 25 (17.1%) underwent colectomy
      by 30 days, 33 (22.6%) by 90 days, and 41 (28.1%) by 1 year. In 21 propensity
      score matched dyads (n = 42) treated with SD or HD, colectomy rates and LOS were
      similar. SD patients more often needed AD (23.8% vs. 0%, P = 0.048) and AD
      patients progressed to colectomy more rapidly within 30 days compared to non-AD
      (P = 0.001). Female sex and hypoalbuminemia were associated with significantly
      increased odds of needing AD on both univariate and multivariate analyses.
      Conclusions: In our propensity score based analysis, receiving accelerated IFX
      dosing after an initial SD infusion was associated with significantly higher 30
      day colectomy rates in hospitalized acute UC patients. The most effective dosing
      strategy in this population remains unclear and prospective randomized studies
      are needed.

PMID- 29462381
TI  - Restorative Surgery in Patients With Primary Sclerosing Cholangitis and
      Ulcerative Colitis Following a Colectomy.
AB  - Background: Studies on surgical procedures in patients with concomitant primary
      sclerosing cholangitis (PSC) and ulcerative colitis (UC) have mainly been
      restricted to single centers. The aim was to compare surgical treatment of UC
      with or without PSC in a nationwide study. Methods: A cohort study including all
      patients diagnosed with UC between 1987 and 2014 in Sweden was undertaken. The
      impact of PSC on the risk of colectomy, the chance of restorative surgery, and
      risk of failure (presence of a stoma) following restorative surgery were
      estimated. Survival analyses were performed using the Kaplan-Meier method and
      multivariable Cox regression models. Results: Of 49 882 UC patients, 2079 had a
      PSC diagnosis at the end of follow-up. The risk of colectomy was unaffected by
      PSC diagnosis, whereas the chance of restorative surgery was elevated in PSC-UC
      patients (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.02-1.44).
      Ileorectal anastomosis (IRA) was performed in 63% of the PSC-UC patients and 43%
      of the non-PSC-UC-patients, and the corresponding numbers for ileal pouch anal
      anastomosis (IPAA) were 35% and 53%. There was no significantly increased risk of
      failure following restorative surgery in PSC patients (HR, 1.44; 95% CI, 0.93
      2.22). In PSC-UC patients, the cumulative failure rates following an IRA at 3 and
      5 years were 15% and 18%, and following an IPAA they were 11% and 18%,
      respectively. Conclusions: Presence of PSC is not associated with the risk of
      colectomy, whereas the chance of restorative surgery in PSC-UC patients is higher
      than in UC alone.

PMID- 29462382
TI  - Prediagnostic Serum Vitamin D Levels and the Risk of Crohn's Disease and
      Ulcerative Colitis in European Populations: A Nested Case-Control Study.
AB  - Background: A low vitamin D status has been put forward as a potential risk
      factor for the development of inflammatory bowel disease (IBD). This study
      investigated the association between prediagnostic circulating vitamin D
      concentrations and dietary intakes of vitamin D, and the risk of Crohn's disease
      (CD) and ulcerative colitis (UC). Methods: Among 359,728 participants of the
      European Prospective Investigation into Cancer and Nutrition cohort, individuals
      who developed CD or UC after enrollment were identified. Each case was matched
      with2 controls by center, gender, age, date of recruitment, and follow-up time.
      At cohort entry, blood samples were collected and dietary vitamin D intakes were
      obtained from validated food frequency questionnaires. Serum 25-hydroxyvitamin D
      levels were measured using liquid chromatography-tandem mass spectrometry.
      Conditional logistic regression was performed to determine the odds of CD and UC.
      Results: Seventy-two participants developed CD and 169 participants developed UC
      after a median follow-up of 4.7 and 4.1 years, respectively. Compared with the
      lowest quartile, no associations with the 3 higher quartiles of vitamin D
      concentrations were observed for CD (p trend = 0.34) or UC (p trend = 0.66).
      Similarly, no associations were detected when serum vitamin D levels were
      analyzed as a continuous variable. Dietary vitamin D intakes were not associated
      with CD (p trend = 0.39) or UC (p trend = 0.83). Conclusions: Vitamin D status
      was not associated with the development of CD or UC. This does not suggest a
      major role for vitamin D deficiency in the etiology of IBD, although larger
      studies are needed to confirm these findings.

PMID- 29462383
TI  - Moving On: Transition Readiness in Adolescents and Young Adults With IBD.
AB  - Background: Inflammatory bowel diseases (IBD) often begins early in life.
      Adolescents and young adults (AYA) with IBD have to acquire behaviors that
      support self-care, effective healthcare decision-making, and self-advocacy to
      successfully transition from pediatric to adult health care. Despite the
      importance of this critical time period, limited empirical study of factors
      associated with transition readiness in AYA exists. This study aimed to describe
      transition readiness in a sample of AYA with IBD and identify associated
      modifiable and nonmodifiable factors. Methods: Seventy-five AYA (ages 16-20) and
      their parents participated. AYA and parents reported on demographics, patient
      provider transition-related communication, and transition readiness. AYA self
      reported on disease self-efficacy. Disease information was abstracted from the
      medical record. Results: Deficits in AYA responsibility were found in knowledge
      of insurance coverage, scheduling appointments, and ordering medication refills.
      Older AYA age, higher AYA disease-management self-efficacy, and increased patient
      provider transition communication were each associated with higher overall
      transition readiness and AYA responsibility scores. Regression analyses revealed
      that older AYA age and increased patient-provider transition-related
      communication were the most salient predictors of AYA responsibility for disease
      management and overall transition readiness across parent and AYA reports.
      Conclusions: AYA with IBD show deficits in responsibility for their disease
      management that have the potential to affect their self-management skills.
      Findings suggest provider communication is particularly important in promoting
      transition readiness. Additionally, it may be beneficial to wait to transition
      patients until they are older to allow them more time to master skills necessary
      to responsibly manage their own healthcare.

PMID- 29462384
TI  - Free and Bioavailable 25-Hydroxyvitamin D Concentrations are Associated With
      Disease Activity in Pediatric Patients With Newly Diagnosed Treatment Naive
      Ulcerative Colitis.
AB  - Background: Vitamin D regulates intestinal epithelial and immune functions, and
      vitamin D receptor deficiency increases the severity of murine colitis.
      Bioavailable 25-hydroxyvitamin D (25(OH)D) is available to target tissues and may
      be a driver of immune function. The aim is to evaluate the relationship of
      bioavailable 25(OH)D to the clinical expression of treatment naive pediatric
      ulcerative colitis (UC). Methods: The PROTECT (Predicting Response to
      Standardized Pediatric Colitis Therapy) study enrolled children <=17 years newly
      diagnosed with UC. Free and total 25(OH)D were directly measured and 25(OH)D
      fractions were compared with disease activity measures. Results: Data were
      available on 388 subjects, mean age 12.7 years, 49% female, 84% with
      extensive/pancolitis. The median (IQR) total 25(OH)D concentration was 28.5
      (23.9, 34.8) ng/mL, and 57% of subjects demonstrated insufficient vitamin D
      status (25(OH)D < 30 ng/mL). We found no evidence of association between total
      25(OH)D and disease activity. Regression models adjusted for age, sex, race, and
      ethnicity demonstrated that an increase from 25th to 75th percentile for
      bioavailable and free 25(OH)D were associated with a mean (95th CI) decrease in
      the Pediatric Ulcerative Colitis Activity Index (PUCAI) of -8.7 (-13.7, -3.6) and
      -3.1 (-5.0, -1.2), respectively. No associations were detected between 25(OH)D
      fractions and fecal calprotectin or Mayo endoscopy score. Conclusions: Vitamin D
      insufficiency is highly prevalent in children with newly diagnosed UC. We found
      associations of free and bioavailable, but not total 25(OH)D, with PUCAI.
      Bioavailable vitamin D may contribute to UC pathophysiology and clinical
      activity.

PMID- 29462385
TI  - The Use of Vedolizumab in Preventing Postoperative Recurrence of Crohn's Disease.
AB  - Background: Clinical and endoscopic recurrence are common after surgery in
      Crohn's disease (CD). Vedolizumab has been increasingly used to treat CD,
      however, its effectiveness in preventing postoperative recurrence remains
      unknown. We aimed to investigate the use of vedolizumab in the postoperative
      setting and compare the risk of recurrence between patients receiving vedolizumab
      and anti-tumor necrosis factor (TNF)-alpha agents. Methods: Medical records of CD
      patients who underwent surgery between April 2014 and June 2016 were reviewed. We
      first analyzed how frequently vedolizumab is used to prevent postoperative
      recurrence and compared the patient characteristics with those being treated with
      other therapies. Furthermore, the rates of endoscopic remission, defined as a
      simple endoscopic score for CD of 0, at 6-12 months after surgery were compared
      between patients receiving vedolizumab and anti-TNF-alpha agents. Clinical,
      biological, and histologic outcomes such as Harvey-Bradshaw index, C-reactive
      protein, and histologic inflammation also were compared between the 2 groups.
      Risks of recurrence were assessed by univariate, multivariate, and propensity
      score-matched analyses. Results: Among 203 patients that underwent a CD related
      surgery, 22 patients received vedolizumab as postoperative treatment. There were
      58, 38, and 16 patients who received anti-TNF-alpha agents, immunomodulators, and
      metronidazole, respectively, whereas 69 patients were monitored without any
      medication. Patients receiving vedolizumab were young and frequently had perianal
      disease. Patients postoperatively treated with vedolizumab or anti-TNF-alpha
      agents were mostly treated with the same agent pre- and postoperatively. Rate of
      endoscopic remission at 6-12 months in the vedolizumab group was 25%, which was
      significantly lower as compared to anti-TNF-alpha agent group (66%, P = 0.01).
      Vedolizumab use was the only factor that was associated with an increased risk of
      endoscopic recurrence on both univariate (odds ratio (OR) 5.58, 95% confidence
      interval (CI) 1.51-24.3, P = 0.005) and multivariate analysis (OR 5.77, 95%CI
      1.71-19.4, P = 0.005). The results were supported by a propensity score-matched
      analysis demonstrating lower rates of endoscopic remission (25 vs 69%, P = 0.03)
      in patients treated with vedolizumab as compared to anti-TNF-alpha agents.
      Conclusion: In the present retrospective cohort study of real-world experience,
      vedolizumab was shown to be commonly used as postoperative treatment for CD
      especially in high risk patients. Multivariate and propensity score-matched
      analyses showed that postoperative endoscopic recurrence in CD was higher with
      vedolizumab than with anti-TNF-alpha agents, but further investigation including
      controlled trials is required before determining the utility of vedolizumab in
      preventing postoperative recurrence of CD.

PMID- 29462387
TI  - Use of Over-the-Scope-Clip System to Treat Ileocolonic Transverse Staple Line
      Leak in Patients With Crohn's Disease.

PMID- 29462386
TI  - Mice with Inflammatory Bowel Disease are Susceptible to Clostridium difficile
      Infection With Severe Disease Outcomes.
AB  - Background: Over the past several decades, there has been a significant increase
      in the incidence of Clostridium difficile infection (CDI) in patients suffering
      from inflammatory bowel disease (IBD). However, a wild-type animal model is not
      available to study these comorbid diseases. Methods: We evaluated the
      susceptibility to CDI of mice with dextran sulfate sodium salt (DSS)-induced
      colitis (IBD mice) with or without antibiotic exposure; we examined the
      histopathology and cytokine response in the concomitant diseases after the model
      was created. Results: No CDI occurs in healthy control mice, wherease the
      incidence of CDI in IBD mice is 40%; however, in IBD mice that received
      antibiotics, the incidence of CDI is 100% and the disease is accompanied by high
      levels of toxins in the mouse feces and sera. Compared to IBD and CDI alone,
      those IBD mice infected with C. difficile have more severe symptoms, toxemia,
      histopathological damage, and higher mortality. Moreover, several proinflammatory
      cytokines and chemokines are significantly elevated in the colon tissues from IBD
      mice infected with C. difficile. Conclusions: We, for the first time, demonstrate
      in an animal model that mice with dextran sulfate sodium induced-inflammatory
      bowel disease are significantly more susceptible to C. difficile infection, and
      that the bacterial infection led to more severe disease and death. These findings
      are consistent with clinical observations, thus, the animal model will permit us
      to study the pathogenesis of these concurrent diseases and to develop therapeutic
      strategies against the comorbidity of IBD and CDI.

PMID- 29462388
TI  - The Impact of NOD2 Variants on Fecal Microbiota in Crohn's Disease and Controls
      Without Gastrointestinal Disease.
AB  - Background/Aims: Current models of Crohn's disease (CD) describe an inappropriate
      immune response to gut microbiota in genetically susceptible individuals. NOD2
      variants are strongly associated with development of CD, and NOD2 is part of the
      innate immune response to bacteria. This study aimed to identify differences in
      fecal microbiota in CD patients and non-IBD controls stratified by NOD2 genotype.
      Methods: Patients with CD and non-IBD controls of known NOD2 genotype were
      identified from patients in previous UK IBD genetics studies and the Cambridge
      bioresource (genotyped/phenotyped volunteers). Individuals with known CD
      associated NOD2 mutations were matched to those with wild-type genotype. We
      obtained fecal samples from patients in clinical remission with low fecal
      calprotectin (<250 ug/g) and controls without gastrointestinal disease. After
      extracting DNA, the V1-2 region of 16S rRNA genes were polymerase chain reaction
      (PCR)-amplified and sequenced. Analysis was undertaken using the mothur package.
      Volatile organic compounds (VOC) were also measured. Results: Ninety-one
      individuals were in the primary analysis (37 CD, 30 bioresource controls, and 24
      household controls). Comparing CD with nonIBD controls, there were reductions in
      bacterial diversity, Ruminococcaceae, Rikenellaceae, and Christensenellaceae and
      an increase in Enterobacteriaceae. No significant differences could be identified
      in microbiota by NOD2 genotype, but fecal butanoic acid was higher in Crohn's
      patients carrying NOD2 mutations. Conclusions: In this well-controlled study of
      NOD2 genotype and fecal microbiota, we identified no significant genotype
      microbiota associations. This suggests that the changes associated with NOD2
      genotype might only be seen at the mucosal level, or that environmental factors
      and prior inflammation are the predominant determinant of the observed dysbiosis
      in gut microbiota.

PMID- 29462389
TI  - Neoplasia and Precursor Lesions of the Female Genital Tract in IBD: Epidemiology,
      Role of Immunosuppressants, and Clinical Implications.
AB  - In this review the risk of breast, ovarian, and endometrial cancer and cervical
      and vulvovaginal (pre)malignant abnormalities in patients with inflammatory bowel
      disease (IBD) with or without immune suppressive treatment will be discussed. So
      far, this has not been studied thoroughly and large studies taking into account
      diverse potential confounding factors are lacking. IBD per se has not been
      associated with development of cervical cancer, yet patients with Crohn's disease
      who smoke, have a younger age at diagnosis or who use(d) thiopurines might be
      more at risk. Other immunosuppressive medication seems not to increase this risk,
      however, as evidence at this point is incomplete, physician awareness and
      prevention by lifestyle counseling, HPV vaccination and (intensified) screening
      are warranted. The risk for breast, endometrial, ovarian, and vulvovaginal cancer
      in IBD patients appears to be comparable to the background population, although
      for breast cancer this may even be decreasedin Crohn's disease specifically.
      Immunosuppressive medication in general does not seem to alter this risk. Earlier
      and more frequent screening for breast cancer than currently conducted in general
      nationwide screening programs is not recommended at this moment. Current
      literature suggests a much lower overall malignancy recurrence rate in IBD
      patients than has been observed previously. More importantly, immune suppressive
      medication does not appear to increase the recurrence risk. Robust epidemiologic
      data on female genital tract cancer are needed.

PMID- 29462390
TI  - Segmental Resection versus Total Proctocolectomy for Crohn's Colitis: What is the
      Best Operation in the Setting of Medically Refractory Disease or Dysplasia?
AB  - Crohn's disease (CD) may affect any part of the gastrointestinal tract. When
      isolated to the colon, and patients become medically refractory, there are
      several surgical options - segmental resection, subtotal colectomy with
      ileorectal anastomosis, or a total proctocolectomy and end ileostomy.
      Unfortunately, surgery does not cure CD, and, regardless of the extent of bowel
      removed, recurrence may be seen in the small bowel. This may lead to need for
      further immunosuppression or surgery. Therefore, when appropriate, a segmental
      colectomy or subtotal colectomy may prevent a permanent ostomy required with a
      total proctocolectomy. In the setting of dysplasia identified on colonoscopy, low
      quality evidence guides our treatment paradigms. Even though identification of
      dysplasia has greatly improved with chromoendoscopy, rates of synchronous or
      metachronous neoplasm remain high. Thus, a total proctocolectomy and end
      ileostomy, whereas a larger operation, may be best for the patient to remove all
      at risk tissue. Further research with prospective or randomized control trials is
      needed to improve our practice guidelines of both scenarios.

PMID- 29462391
TI  - Combination Immunosuppression in IBD.
AB  - Whether to use biologic treatment for inflammatory bowel disease as monotherapy
      or in combination with immunosuppressives has been a matter of debate in the last
      2 decades. Combination therapy was not superior in any of the registration trials
      for Crohn's disease and ulcerative colitis for TNF antagonists, vedolizumab, or
      ustekinumab. It needs to be mentioned, though, that none of these trials were
      powered to detect such differences, and that many patients entered the trial
      after having failed conventional immunosuppressives.Postmarketing studies
      revealed that patients on background immunosuppression have a lower risk of
      immunogenicity (often resulting in infusion/injection reactions) than patients on
      monotherapy. In the SONIC and UC-SUCCESS trials, superiority of the combination
      azathioprine-infliximab was demonstrated in Crohn's disease and ulcerative
      colitis, respectively. This trial design has not been used with any other
      biologic for IBD, so far. Meanwhile, it has also become clear that combination
      treatment with TNF antagonists is associated with increased toxicity, mainly
      infections, but also malignancy such as lymphoproliferative disease. This
      toxicity could perhaps be reduced by using lower doses of immunosuppressives, a
      strategy that has been shown to be equally potent in reducing immunogenicity.
      Additionally, combination treatment could be used for a limited period of time
      (12 months or even shorter) since most immunogenicity develops in the beginning
      of the biologic treatment. Patients who develop anti-drug-antibodies later on can
      often be rescued by reintroduction of thiopurines or methotrexate.In summary,
      combination treatment is certainly beneficial with infliximab, at least in the
      first 12 months of treatment. With other TNF antagonists, vedolizumab, and
      ustekinumab, the available data do not offer clear guidance. In patients without
      increased risk of toxicity, and certainly in those with limited treatment
      options, it may be wise to offer combination treatment with all biologics for the
      time being and at least during the initiation phase.

PMID- 29462392
TI  - Venous Thromboembolism in Hospitalized Inflammatory Bowel Disease Patients with
      Clostridium difficile Infection.

PMID- 29462393
TI  - Increased Rate of Venous Thromboembolism in Hospitalized Inflammatory Bowel
      Disease Patients With Clostridium difficile Infection.

PMID- 29462394
TI  - Nondysplastic Ulcerative Colitis Has High Levels of the Homologous Recombination
      Repair Protein NUCKS1 and Low Levels of the DNA Damage Marker Gamma-H2AX.
AB  - Background: The colon and rectum are continuously exposed to oxidative stress
      that generates reactive oxygen species, which are a major cause of DNA double
      strand breaks (DSB). Furthermore, chronic inflammatory diseases such as
      ulcerative colitis (UC) are characterized by an excess of reactive nitrogen
      species that can also lead to DNA double-strand breakage and genomic instability.
      We investigated the expression of the nuclear casein kinase and cyclin-dependent
      kinase substrate 1 (NUCKS1) protein in UC and sporadic colorectal cancer (CRC)
      due to its involvement in both DNA double-strand break repair and inflammatory
      signaling. Methods: NUCKS1 expression and expression of the DNA double-strand
      break marker gamma-H2AX (gammaH2AX) were assessed in formalin-fixed, paraffin
      embedded UC and CRC patient biopsies using peroxidase immunohistochemistry.
      Expression levels for both proteins were evaluated together with previously
      published expression-level data for hTERT and TP53 proteins in the same material.
      Results: Nondysplastic UC lesions had 10-fold lower gammaH2AX expression and
      approximately 4-fold higher NUCKS1 expression compared with sporadic CRC,
      indicating minimal DNA DSB damage and heightened DNA DSB repair in these lesions,
      respectively. NUCKS1 expression in UC tended to decrease with increasing grades
      of dysplasia, whereas gammaH2AX, hTERT, and TP53 expression tended to increase
      with increasing grades of dysplasia. The highest gammaH2AX expression was seen in
      sporadic CRC, indicating considerable DNA DSB damage, whereas the highest NUCKS1
      expression and hTERT expression were seen in nondysplastic UC. Conclusions:
      Overall, our data suggest that NUCKS1 may be involved in DNA DSB repair and/or
      inflammatory signaling in UC, but a more thorough investigation of both pathways
      in UC is warranted.

PMID- 29462395
TI  - Infliximab for Crohn's Disease: More Than 13 Years of Real-world Experience.
AB  - Background: The purpose of this study was to compare the long-term safety of
      infliximab and nonbiologic agents as Crohn's disease (CD) therapy. Methods:
      Patients with CD were prospectively evaluated in this large, observational
      registry. Results: Patients (n = 6273) participated in this observational
      registry from July 1999 through March 2012; 3440 (54.8%) received infliximab
      (20,971 patient-years), and 2833 (45.2%) received other treatments only (14,806
      patient-years). Overall, 59,875 infliximab infusions were administered (80%, 5
      mg/kg); 3006 (89.9%) patients received >=2 infusions. Adverse events (AEs), most
      commonly those related to CD (eg, abdominal pain, diarrhea), and serious AEs
      occurred at a higher rate among infliximab-treated patients. Mortality (0.57/100
      patient-years, 0.67/100 patient-years) and malignancy rates (0.69/100 patient
      years, 0.71/100 patient-years) for infliximab-treated and other-treatments-only
      patients, respectively, were generally similar. Serious infection rates were
      higher for infliximab-treated (2.15/100 patient-years) than other-treatments-only
      patients (0.86/100 patient-years). Infliximab dose was not associated with
      mortality or serious infection. An increased risk of serious infection was
      observed with age (>52 years vs <=30 years) when examined in infliximab-treated
      patients. Nonserious cerebrovascular accidents (13 events, 0.06/100 patient
      years; 5 events, 0.03/100 patient-years) and pulmonary embolisms (11 events,
      0.05/100 patient-years; 4 events 0.03/100 patient-years) also occurred at higher
      rates among infliximab-treated patients than other-treatments-only patients.
      Conclusions: Through more than 13 years of registry experience and an overall
      median duration of patient follow-up >6 years, mortality was similar between the
      infliximab-treated and other-treatments-only groups. These final cumulative
      results are representative of real-world experience among infliximab-treated
      patients with CD and are consistent with the known risks of disease activity and
      tumor necrosis factor antagonist therapy.

PMID- 29462396
TI  - Incorporation of Scribes Into the Inflammatory Bowel Disease Clinic Improves
      Quality of Care and Physician Productivity.
AB  - Background: Electronic health records (EHRs), despite their positive attributes,
      increase physician workload and decrease efficiency. The aim of this study was to
      evaluate the impact of scribes in the Inflammatory Bowel Disease Clinic on
      improvement of the physician-patient relationship, physician productivity,
      clinical efficiency, and achievement of some Physician Quality Reporting System
      (PQRS) metrics. Methods: We analyzed of pre- and postscribe data between fiscal
      years 2015 (FY15) and 2016 (FY16) using data from patients at the Inflammatory
      Bowel Clinic at the University of Florida. The main outcomes were patient
      satisfaction scores (PSS), qualitative physician interview, clinic appointment
      lengths, work relative value units (wRVUs), level of coding, revenue, and PQRS
      data on bone density screening and vaccination. Results: PSS increased from
      6.8/10 to 9.2/10 (P < 0.01), clinic appointment length decreased by 13.5 minutes
      (P < 0.05), and documentation stress decreased. Clinic visits increased by 76,
      leading to an increase in work RVUs by 332.55, total charges billed by $71,439,
      and total charges collected by $27,387 between the first quarters of FY15 and
      FY16. The extra revenue for the first quarter was 536% higher than the salary of
      the scribe for the same period ($4302.84). There was a 1.8-fold increase in
      referrals for bone density scans and 2.9-fold and 4.8-fold increases in
      vaccination rates for influenza and pneumonia, respectively. Conclusions: The use
      of scribes improved the physician-patient relationship, clinical efficiency,
      physician productivity, bone density screening, and vaccinations for flu and
      pneumonia. If adopted by health systems, it may lead to significant cost savings
      and improved clinical outcomes.

PMID- 29462397
TI  - Duodenal Crohn's Disease.
AB  - Symptomatic duodenal Crohn's disease (CD) is an uncommon disease presentation,
      especially in isolation. The most common duodenal disease phenotype is
      stricturing disease rather than inflammatory or perforating. Most patients are
      asymptomatic and are therefore diagnosed incidentally by cross-sectional imaging
      or endoscopy. Medical management includes proton pump inhibitor therapy and
      immunosuppressive therapy including corticosteroids, immunomodulatory therapy,
      and biologic therapy. Symptomatic strictures can often be treated medically or
      endoscopically, and do not always require surgery. Surgical options include
      resection with primary anastomosis, bypass with a gastrojejunostomy, and
      strictureplasty. Treatment recommendations are largely based on limited evidence
      from small series and expert opinion. Therefore, the optimal treatment algorithm
      remains largely subjective and undefined.

PMID- 29462398
TI  - Full Interchangeability in Regard to Immunogenicity Between the Infliximab
      Reference Biologic and Biosimilars CT-P13 and SB2 in Inflammatory Bowel Disease.
AB  - Background: Infliximab (IFX) biosimilars CT-P13 and SB2 have comparable efficacy,
      safety, and immunogenicity to the originator Remicade (RMC). However, concerns
      about cross-switching patients between the 3 brands were raised in the absence of
      cross reactivity data between them. We aimed to determine whether antibodies to
      infliximab (ATI) in inflammatory bowel disease (IBD) patients cross-react with
      RMC, CT-P13, and SB2. Methods: Based on previous ATI status, samples from 34
      patients participating in the BIOSIM01 study (13 RMC, 9 CT-P13, and 12 switchers)
      were selected. Patients were treated with either RMC only, or CT-P13 only, or
      with RMC switched to CT-P13. Additionally, 28 IFX-naive patients were assayed as
      controls. In total, 180 samples were analyzed. ATI trough levels were measured in
      parallel with 3 different bridging Enzyme Linked Immunosorbent Assays constructed
      using the 3 drugs. Spearman's coefficient and percentages of agreement were used
      to study the correlation between each assay. Results: In total, 76 samples out of
      152 IFX-treated patient samples were ATI-positive (30 RMC, 14 CT-P13, and 32
      switchers). All resulted ATI-positive when either CT-P13 or SB2 bridging assays
      were used. The overall percentage of agreement was 100% when compared either with
      CT-P13 or SB2 assays. No significant differences were found among ATI levels and
      coefficients (Spearman's 0.98 to 1.0, P < 0.0001). Conclusions: ATI of RMC
      treated, CT-P13-treated or RMC to CT-P13 switched patients show full cross
      reactivity with CT-P13 and SB2. Findings suggest that immunodominant epitopes in
      the reference and CT-P13 drugs are equally present in SB2. Data support full
      interchangeability between biosimilars in regard to immunogenicity.

PMID- 29462399
TI  - Mendelian Disease Associations Reveal Novel Insights into Inflammatory Bowel
      Disease.
AB  - Background: Monogenic diseases have been shown to contribute to complex disease
      risk and may hold new insights into the underlying biological mechanism of
      Inflammatory Bowel Disease (IBD). Methods: We analyzed Mendelian disease
      associations with IBD using over 55 million patients from the Optum's
      deidentified electronic health records dataset database. Using the significant
      Mendelian diseases, we performed pathway enrichment analysis and constructed a
      model using gene expression datasets to differentiate Crohn's disease (CD),
      ulcerative colitis (UC), and healthy patient samples. Results: We found 50
      Mendelian diseases were significantly associated with IBD, with 40 being
      significantly associated with both CD and UC. Our results for CD replicated those
      from previous studies. Pathways that were enriched consisted of mainly immune and
      metabolic processes with a focus on tolerance and oxidative stress. Our 3-way
      classifier for UC, CD, and healthy samples yielded an accuracy of 72%.
      Conclusions: Mendelian diseases that are significantly associated with IBD may
      reveal novel insights into the genetic architecture of IBD.

PMID- 29462400
TI  - Mendelian Diseases and Inflammatory Bowel Disease-Data Mining for Genetic Risk
      and Disease-Associated Confounders.

PMID- 29462401
TI  - Letter to the Editor: Missed Meals While Hospitalized for UC.

PMID- 29462402
TI  - Full Interchangeability in Regards to Immunogenicity Between the Infliximab
      Reference Biologic and Biosimilars CT-P13 and SB2 in Inflammatory Bowel Disease.

PMID- 29462403
TI  - Transferable vancomycin resistance in clade B commensal-type Enterococcus
      faecium.
AB  - Objectives: Vancomycin-resistant Enterococcus faecium is a leading cause of MDR
      hospital infection. Two genetically definable populations of E. faecium have been
      identified: hospital-adapted MDR isolates (clade A) and vancomycin-susceptible
      commensal strains (clade B). VanN-type vancomycin resistance was identified in
      two isolates of E. faecium recovered from blood and faeces of an
      immunocompromised patient. To understand the genomic context in which VanN
      occurred in the hospitalized patient, the risk it posed for transmission in the
      hospital and its origins, it was of interest to determine where these strains
      placed within the E. faecium population structure. Methods: We obtained the
      genome sequence of the VanN isolates and performed comparative and functional
      genomics of the chromosome and plasmid content. Results: We show that, in these
      strains, VanN occurs in a genetic background that clusters with clade B E.
      faecium, which is highly unusual. We characterized the chromosome and the
      conjugative plasmid that carries VanN resistance in these strains, pUV24. This
      plasmid exhibits signatures of in-host selection on the vanN operon regulatory
      system, which are associated with a constitutive expression of vancomycin
      resistance. VanN resistance in clade B strains may go undetected by current
      methods. Conclusions: We report a case of vancomycin resistance in a commensal
      lineage of E. faecium responsible for an atypical bacteraemia in an
      immunocompromised patient. A reservoir of transferable glycopeptide resistance in
      the community could pose a concern for public health.

PMID- 29462405
TI  - Gut barrier function: Effects of (antibiotic) growth promoters on key barrier
      components and associations with growth performance.
AB  - The gut barrier, comprising the microbiota and their products, mucus layers, host
      derived antimicrobial compounds [e.g., host defense peptides (HDP), IgA],
      epithelium, and underlying immune tissues, performs the essential function of
      preventing the passage of harmful microorganisms and substances into the body,
      while enabling the acquisition of dietary nutrients. Antibiotic growth promoters
      (AGP) are widely accepted as the "gold standard" of performance-enhancing feed
      additives, which had become integral and valuable components of modern, efficient
      animal production, but are now being phased out in many parts of the world. This
      review, therefore, examines the reported effects of AGP on the key components of
      gut barrier function, particularly where corresponding (positive) growth
      performance data were provided to indicate that any changes were beneficial, and
      some important trends do emerge. Certain bacterial families (e.g.,
      Lachnospiraceae), genera (e.g., Faecalibacterium, Propionibacterium, and
      Ruminococcus), or species (e.g., F. prausnitzii, B. fragilis, and some
      Lactobacillus spp.) have been reported to increase with AGP use, are associated
      with improved growth performance, and show benefit across species, which may be
      related to their production of short-chain fatty acids (SCFA). Various studies
      have investigated the effects of AGP on mucus-related parameters (e.g., goblet
      cell size, density, and mucin mRNA expression) but these do not always seem to
      correlate well with the actual physical characteristics of the mucus layer(s).
      Surprisingly, there are little data relating to HDP or IgA, even though they have
      recognized benefits. There are clear AGP benefits on epithelial structure and
      function (e.g., nutrient digestibility), and these may (currently) provide the
      most reliable indicators of the efficacy of growth promoters. Data investigating
      effects on gut immune parameters (e.g., cell populations, cytokines, and
      chemokines), with corresponding growth performance, are limited and require
      further detailed interrogation. This review highlights both important
      observations related to the effects of AGP on key gut barrier components, with
      associated growth performance, and areas that require further investigation, thus
      providing an informative basis for assessing the potential of AGP alternatives.

PMID- 29462406
TI  - Long-term non-institutionalized survival and rehospitalization after surgical
      aortic and mitral valve replacements in a large provincial cardiac surgery
      centre.
AB  - OBJECTIVES: Long-term quality of life following open surgical valve replacement
      is an increasingly important outcome to patients and their caregivers. This study
      examines non-institutionalized survival and rehospitalization within our surgical
      aortic valve replacement (AVR) and mitral valve replacement (MVR) populations.
      METHODS: A retrospective single-centre study of all consecutive open surgical
      valve replacements between 1995 and 2014 was undertaken. Clinical data were
      linked to provincial administrative data for 3219 patients who underwent AVR, MVR
      or double (aortic and mitral) valve replacement with or without concomitant
      coronary artery bypass grafting (CABG). Non-institutionalized survival and
      cumulative incidence of rehospitalization was examined up to 15 years. RESULTS:
      Follow-up was complete for 96.9% of the 2146 patients who underwent AVR +/- CABG
      (66.7% of the overall cohort), 878 who underwent MVR +/- CABG (27.3%) and 195 who
      underwent double (aortic and mitral) valve replacement +/- CABG (6.0%) with a
      median follow-up time of 5.6 years. Overall non-institutionalized survival was
      35.4% at 15 years, and the cumulative incidence of rehospitalization was 34.4%,
      63.2% and 87.0% at 1, 5 and 15 years, respectively, without significant
      differences between valve procedure cohorts. Both non-institutionalized survival
      and cumulative incidence of rehospitalization improved in more recent eras,
      despite increasing age and comorbidities. CONCLUSIONS: Non-institutionalized
      survival and rehospitalization data for up to 15 years suggest good functional
      outcomes long after surgical AVR and/or MVR. Continued improvements are seen in
      these metrics over the past 2 decades. This provides a unique insight into the
      quality of life after surgical valve replacement in the ageing demographics with
      valvular heart disease.

PMID- 29462404
TI  - vmPFC activation during a stressor predicts positive emotions during stress
      recovery.
AB  - Despite accruing evidence showing that positive emotions facilitate stress
      recovery, the neural basis for this effect remains unclear. To identify the
      underlying mechanism, we compared stress recovery for people reflecting on a
      stressor while in a positive emotional context with that for people in a neutral
      context. While blood-oxygen-level dependent data were being collected,
      participants (N = 43) performed a stressful anagram task, which was followed by a
      recovery period during which they reflected on the stressor while watching a
      positive or neutral video. Participants also reported positive and negative
      emotions throughout the task as well as retrospective thoughts about the task.
      Although there was no effect of experimental context on emotional recovery, we
      found that ventromedial prefrontal cortex (vmPFC) activation during the stressor
      predicted more positive emotions during recovery, which in turn predicted less
      negative emotions during recovery. In addition, the relationship between vmPFC
      activation and positive emotions during recovery was mediated by decentering-the
      meta-cognitive detachment of oneself from one's feelings. In sum, successful
      recovery from a stressor seems to be due to activation of positive emotion
      related regions during the stressor itself as well as to their downstream effects
      on certain cognitive forms of emotion regulation.

PMID- 29462407
TI  - Transitional changes in the incidence of osteonecrosis in systemic lupus
      erythematosus patients: focus on immunosuppressant agents and glucocorticoids.
AB  - Objective: The purpose of this study was to investigate transitional changes in
      the incidence of glucocorticoid-associated osteonecrosis in SLE patients, with a
      focus on immunosuppressive agent and glucocorticoid consumption. Methods: We
      retrospectively registered 185 SLE patients with 740 joints, who were newly
      diagnosed and hospitalized for initial high-dose glucocorticoid therapy from 1986
      to 2015. Immunosuppressive agent, glucocorticoid dose, age, sex, organ lesion at
      hospitalization, complement (C3, C4, CH50) and anti-DNA antibody before initial
      glucocorticoid therapy, the frequency of use of anticoagulant and antilipidemic
      drugs, and incidence of osteonecrosis were documented. Results: Based on trends
      in immunosuppressive agent use, 116 patients treated from 1986 to 1999, before
      calcineurin inhibitors were introduced, comprised the past group, and 69 patients
      treated from 2000 to 2015 comprised the recent group. Patient characteristics
      (age, sex and organ lesion at hospitalization, complement, anti-DNA antibody, the
      frequency of use of anticoagulant and antilipidemic drugs) were similar between
      groups. Glucocorticoid doses were significantly lower in the recent group than in
      the past group (highest daily glucocorticoid dose, 45.7 vs 59.0 mg/day,
      respectively; dose per weight, 0.88 vs 1.16 mg/day/kg, respectively; and
      cumulative dose at 3 months, 3118 vs 3985 mg). The incidence of osteonecrosis was
      significantly lower in the recent group than in the past group (26.4 vs 41.0%,
      respectively), particularly in the knee (25.4 vs 46.6%, respectively).
      Conclusion: The incidence of glucocorticoid-associated osteonecrosis in SLE
      patients decreased in association with a decrease in glucocorticoid
      administration after introduction of immunosuppressant agents.

PMID- 29462408
TI  - Effects of in ovo administration of L-ascorbic acid on broiler hatchability and
      its influence on the effects of pre-placement holding time on broiler quality
      characteristics,.
AB  - The current study was conducted to determine the possible effects of the in ovo
      administration of different dosages of L-ascorbic acid (AA) to broiler hatching
      eggs on hatchability and its potential for reducing the adverse effects of
      delayed placement.A total of 702 broiler hatching eggs was hand-injected at 17 d
      of incubation (DOI) with 100 MUL of sterile saline (0.85%) alone or containing
      0.5, 1.5, 4.5, or 13.5 mg AA. Hatchability was recorded every 5 h from 480 h to
      505 hours. Results showed that AA injection did not affect embryo BW as
      percentage of set egg weight or yolk sac weight as percentage of embryo weight at
      19.5 DOI. The hatching time of all embryos that received an AA in ovo injection
      was between 480 and 495 h of incubation, and significantly fewer embryos hatched
      before 480 h in comparison to non-injected controls. Hatchability (above 92% in
      all groups) was not significantly affected by injection treatment. However,
      fertile eggs injected with saline containing 4.5 mg AA had the highest
      hatchability. At 21 DOI, hatching BW as a percentage of set egg weight and yolk
      sac weight as a percentage of BW were numerically higher in AA injection groups.
      An in ovo injection of AA at a 13.5 mg/egg level resulted in a numerically higher
      BW as a percentage of set egg weight. The in ovo injection of AA did not reduce
      the adverse effects of a 48-hour posthatch pre-placement holding time on BW or on
      yolk sac absorption. Overall, in ovo injection of L-ascorbic acid (0.5 to 13.5
      mg/egg) into fertile broiler hatching eggs at 17 DOI did not negatively affect
      hatchability or embryo development, and did not prevent the negative effects of a
      48-hour posthatch holding time on BW and yolk sac absorption. The range of
      tolerance as well as the optimal dosage of in ovo-injected AA warrants future
      study.

PMID- 29462409
TI  - The Behavior of Metropolis-Coupled Markov Chains When Sampling Rugged
      Phylogenetic Distributions.
AB  - Bayesian phylogenetic inference relies on the use of Markov chain Monte Carlo
      (MCMC) to provide numerical approximations of high-dimensional integrals and
      estimate posterior probabilities. However, MCMC performs poorly when posteriors
      are very rugged (i.e., regions of high posterior density are separated by regions
      of low posterior density). One technique that has become popular for improving
      numerical estimates from MCMC when distributions are rugged is Metropolis
      coupling (MC$^3$). In MC$^3$, additional chains are employed to sample flattened
      transformations of the posterior and improve mixing. Here, we highlight several
      underappreciated behaviors of MC3. Notably, estimated posterior probabilities may
      be incorrect but appear to converge, when individual chains do not mix well,
      despite different chains sampling trees from all relevant areas in tree space.
      Counterintuitively, such behavior can be more difficult to diagnose with
      increased numbers of chains. We illustrate these surprising behaviors of MC$^3$
      using a simple, non-phylogenetic example and phylogenetic examples involving both
      constrained and unconstrained analyses. To detect and mitigate the effects of
      these behaviors, we recommend increasing the number of independent analyses and
      varying the temperature of the hottest chain in current versions of Bayesian
      phylogenetic software. Convergence diagnostics based on the behavior of the
      hottest chain may also help detect these behaviors and could form a useful
      addition to future software releases.

PMID- 29462411
TI  - Radiofrequency Energy and Electrode Proximity Influences
      Stereoelectroencephalography-Guided Radiofrequency Thermocoagulation Lesion Size:
      An In Vitro Study with Clinical Correlation.
AB  - BACKGROUND: Radiofrequency thermocoagulation of epileptogenic foci via
      stereoelectroencephalography (SEEG) electrodes has been suggested as a treatment
      for medically intractable epilepsy, but reported outcomes have been suboptimal,
      possibly because lesions generated using conventional high-energy radiofrequency
      parameters are relatively small. OBJECTIVE: To describe a technique of delivering
      low energy across separate SEEG electrodes in order to create large confluent
      radiofrequency lesions. METHODS: The size and configuration of radiofrequency
      lesions using different radiofrequency intensity and interelectrode distance was
      assessed in egg whites. Magnetic resonance images (MRI) from 3 patients who had
      undergone radiofrequency lesion creation were evaluated to determine the
      contribution of lesion intensity and electrode separation on lesion size.
      Electroencephalography, MRI, and clinical data were assessed before and after
      lesion creation. RESULTS: Both in Vitro and in Vivo analysis revealed that less
      energy paradoxically produced larger lesions, with the largest possible lesions
      produced when radiofrequency power was applied for long duration at less than 3
      W. Linear separation of electrodes also contributed to lesion size, with largest
      lesions produced when electrodes were separated by a linear distance of between 5
      and 12 mm. Clinical lesions produced using these parameters were large and
      resulted in improvement in interictal and ictal activity. CONCLUSION:
      Radiofrequency lesions produced using low-energy delivery between SEEG electrodes
      in close proximity can produce a large lesion. These findings might have
      advantages for treatment of focal epilepsy.

PMID- 29462410
TI  - Changes in Brain-Derived Neurotrophic Factor Expression Influence Sleep-Wake
      Activity and Homeostatic Regulation of Rapid Eye Movement Sleep.
AB  - Study Objectives: Brain-derived neurotrophic factor (BDNF) expression and
      homeostatic regulation of rapid eye movement (REM) sleep are critical for
      neurogenesis and behavioral plasticity. Accumulating clinical and experimental
      evidence suggests that decreased BDNF expression is causally linked with the
      development of REM sleep-associated neuropsychiatric disorders. Therefore, we
      hypothesize that BDNF plays a role in sleep-wake (S-W) activity and homeostatic
      regulation of REM sleep. Methods: Male and female wild-type (WT; BDNF +/+) and
      heterozygous BDNF (KD; BDNF +/-) rats were chronically implanted with S-W
      recording electrodes to quantify baseline S-W activity and REM sleep homeostatic
      regulatory processes during the light phase. Results: Molecular analyses revealed
      that KD BDNF rats had a 50% decrease in BDNF protein levels. During baseline S-W
      activity, KD rats exhibited fewer REM sleep episodes that were shorter in
      duration and took longer to initiate. Also, the baseline S-W activity did not
      reveal any sex difference. During the 3-hour selective REM sleep deprivation, KD
      rats failed to exhibit a homeostatic drive for REM sleep and did not exhibit
      rebound REM sleep during the recovery S-W period. Conclusion: Interestingly, both
      genotypes did not reveal any sex difference in the quality and/or quantity of REM
      sleep. Collectively, these results, for the first time, unequivocally demonstrate
      that an intact BDNF system in both sexes is a critical modulator for baseline and
      homeostatic regulation of REM sleep. This study further suggests that
      heterozygous BDNF knockdown rats are a useful animal model for the study of the
      cellular and molecular mechanisms of sleep regulation and cognitive functions of
      sleep.

PMID- 29462412
TI  - Meta-analysis: explicit value of mono-component proteases in monogastric diets.
AB  - A meta-analysis was conducted to investigate the effect of mono-component
      proteases on performance and apparent ileal amino acid digestibility (AIAAD, %)
      in monogastrics. A total of 67 experimental trials were included in the meta
      analysis from published and internal reports, contributing 467 lines of data.
      Poultry and swine data accounted for 81 and 19% of the dataset, respectively.
      Forty-four different proteases were included in the meta-analysis, accounting for
      commercial and non-commercial products. Mixed Model analysis was used to assess
      protease effect and the influence of inherent characteristics of the control on
      protease response. The mean performance response to protease was a reduction in
      feed conversion ratio (FCR) for poultry (1%, P < 0.05) and swine (4%, P > 0.05).
      The mean relative effect of protease on AIAAD over the control was 1.6 +/- 0.3%,
      ranging from 1.2% for Arg, Phe and Trp to 2.6% for Cys. For the majority of amino
      acids, inherent AIAAD of control diets influenced (P < 0.05) the magnitude of the
      protease response such that, as inherent digestibility increased, the effect of
      protease on amino acid digestibility decreased. The dataset was subsequently
      divided into 2 subgroups: diets with and without other enzymes, namely non-starch
      polysaccharide degrading enzymes (NSPase) and phytase. Addition of protease in
      diets containing no other enzymes significantly (P < 0.05) increased AIAAD for
      the majority of amino acids and tended (P < 0.10) to improve Met, Trp, Pro, Gly,
      and Tyr. However, when other enzymes were included in the experiment, the
      beneficial effect of protease on AIAAD was lost (P > 0.05). These findings
      suggest that when other enzymes are already included in the diet, addition of
      protease requires further justification for use in monogastric diets.

PMID- 29462414
TI  - Primary glioblastoma cells for precision medicine: a quantitative portrait of
      genomic (in)stability during the first 30 passages.
AB  - Background: Primary glioblastoma cell (GC) cultures have emerged as a key model
      in brain tumor research, with the potential to uncover patient-specific
      differences in therapy response. However, there is limited quantitative
      information about the stability of such cells during the initial 20-30 passages
      of culture. Methods: We interrogated 3 patient-derived GC cultures at dense time
      intervals during the first 30 passages of culture. Combining state-of-the-art
      signal processing methods with a mathematical model of growth, we estimated
      clonal composition, rates of change, affected pathways, and correlations between
      altered gene dosage and transcription. Results: We demonstrate that GC cultures
      undergo sequential clonal takeovers, observed through variable proportions of
      specific subchromosomal lesions, variations in aneuploid cell content, and
      variations in subpopulation cell cycling times. The GC cultures also show
      significant transcriptional drift in several metabolic and signaling pathways,
      including ribosomal synthesis, telomere packaging and signaling via the mammalian
      target of rapamycin, Wnt, and interferon pathways, to a high degree explained by
      changes in gene dosage. In addition to these adaptations, the cultured GCs showed
      signs of shifting transcriptional subtype. Compared with chromosomal aberrations
      and gene expression, DNA methylations remained comparatively stable during
      passaging, and may be favorable as a biomarker. Conclusion: Taken together, GC
      cultures undergo significant genomic and transcriptional changes that need to be
      considered in functional experiments and biomarker studies that involve primary
      glioblastoma cells.

PMID- 29462413
TI  - Dietary oregano (Origanum vulgare L.) aqueous extract improves oxidative
      stability and consumer acceptance of meat enriched with CLA and n-3 PUFA in
      broilers.
AB  - The effect of a dietary oregano aqueous extract on meat fatty acid profile,
      quality, and consumer acceptance in chickens fed a diet rich in polyunsaturated
      fatty acids (PUFA) was evaluated in 3 consecutive trials.For each trial, 171 day
      old Ross 308 chicks were randomly divided in replicates of 19 birds each and
      assigned to one of 3 experimental diets: 1) basal control diet, 2) basal diet
      supplemented with 0.2 g/kg of oregano aqueous extract, and 3) basal diet
      supplemented with 150 ppm of vitamin E (as positive control). To better analyze
      the antioxidant activity of both oregano and vitamin E, all the experimental
      diets were enriched with a fatty acid supplement consisting in a mixture of PUFA
      at the same dose (1.16 %) in both starter and finisher feeds. Oregano
      supplementation positively influenced (P < 0.05) broiler live performance. No
      differences were observed in physicochemical or proximal composition or in total
      fatty acid composition of breast meat. Dietary oregano influenced meat
      composition in terms of total phenolic content, antioxidant capacity, and
      thiobarbituric acid-reactive substances, improving meat resistance to oxidation,
      compared to both other groups. During consumer tests, meat from the 3 dietary
      groups obtained the same liking score in a blind session. Under informed
      condition, consumer perception was positively influenced by labeling for all the
      considered attributes. Furthermore, consumers showed a higher expectation for
      meat derived from chickens fed the oregano extract when compared to that deriving
      from the other 2 groups.Results obtained in the present study allow stating that
      using oregano aqueous extract in diets enriched with PUFA can represent a valid
      solution to increase live weight of chickens, improve resistance to oxidation of
      meat, and positively influence consumer perception of poultry meat.

PMID- 29462415
TI  - Healthcare improvement measures in risk management and patient satisfaction.

PMID- 29462416
TI  - Navigating the health-work interface-vocational rehabilitation in the UK.

PMID- 29462417
TI  - Screening for latent tuberculosis in UK health care workers.

PMID- 29462418
TI  - What should we tell shift workers to do to reduce their cancer risk?

PMID- 29462419
TI  - Effect of supplemental phytase and xylanase in wheat-based diets on prececal
      phosphorus digestibility and phytate degradation in young turkeys.
AB  - This study aimed to investigate the effect of phytase and a combination of
      phytase and xylanase on the prececal phosphorus digestibility (pcdP) of wheat
      based diets in turkeys. A low-P basal diet (BD) based on cornstarch and soybean
      meal, and 2 diets containing 43% of different wheat genotypes (genotype diets GD6
      or GD7) were fed to turkeys from 20 to 27 d of age. Diets were fed either without
      enzyme supplementation or supplemented with phytase (500 FTU/kg) or a combination
      of phytase and xylanase (16,000 BXU/kg). At 27 d of age, digesta were sampled
      from the lower ileum of animals to determine pcdP and pc myo-inositol 1,2,3,4,5,6
      hexakis (dihydrogen phosphate) (InsP6) disappearance, and to analyze the
      concentrations of lower inositol phosphate isomers. Similar pcdP was observed in
      non-supplemented BD and GD (~36%). Phytase alone increased the pcdP in all diets
      by 8 to 12%, but a beneficial effect of xylanase was found only for BD. Similar
      results were found for pc InsP6 disappearance, although xylanase addition
      compared to phytase alone decreased pc InsP6 disappearance in GD7 compared to
      phytase alone. Animals fed GD7 performed better than those fed GD6; however,
      these differences could not be linked to the pcdP. The pattern of lower inositol
      phosphates in digesta also changed with enzyme supplementation, resulting in
      lower proportions of InsP5 and higher proportions of InsP4. Phytase alone
      decreased Ins(1,2,3,4,6)P5 but increased D-Ins(1,2,3,4,5)P5 and D-Ins(1,2,5,6)P4
      concentrations. An additional increase in D-Ins(1,2,3,4,5)P5 and D-Ins(1,2,5,6)P4
      concentrations was achieved with xylanase, although for the former isomer, this
      was observed only with GD. These results indicate that enzyme supplementation
      alters the pc degradation of InsP6, and that combining both enzymes had a minor
      additional effect on the pcdP from wheat-based diets when compared to phytase
      alone.

PMID- 29462420
TI  - Evaluation of a coccidia vaccine using spray and gel applications.
AB  - Coccidiosis is an economically significant disease of poultry caused by species
      of Eimeria, a parasitic protozoan. Disease can result in poor feed conversion,
      reduced weight gain, and can lead to the development of necrotic enteritis. For
      prevention of coccidiosis, poultry are commonly vaccinated with a live,
      sporulated oocysts mass applied with a vaccination cabinet in the hatchery.
      Traditionally, coccidia vaccines have been applied by coarse spray in a water
      based diluent, however, new technology using gel diluents has entered the US
      market. Gel diluents can have variable viscosities and are "dropped" onto chicks
      with an applicator bar. It is thought that gel droplets remain intact on the
      birds for longer than water based droplets, allowing more time for preening and
      ingestion of oocysts. In this experiment, the efficacy of a commercial coccidia
      vaccine applied with a water based diluent, a more viscous gel diluent, and a
      less viscous gel diluent was compared. Fecal samples were collected at multiple
      time points post-vaccination to quantify vaccine oocyst shedding. Shedding in the
      first cycle (days 5 to 8 post-vaccination) was related to the number of oocysts
      received from each application method, where the groups receiving higher doses
      shed more oocysts. However, a decrease in shedding was seen for the more viscous
      gel group in the second cycle (days 12 to 15 post-vaccination). Chickens were
      challenged with Eimeria maxima oocysts and 7 days post-challenge body weight
      gains and gross and microscopic lesions were recorded to evaluate protection
      levels for the different vaccine applications. All vaccinated groups appeared to
      be protected based on body weight gain and lesion scoring. The results of this
      project indicate that all vaccine applications are effective at protecting
      against Eimeria maxima challenge when using a proper dose of vaccine that allows
      for repeated oocyst cycling in the litter post-vaccination.

PMID- 29462421
TI  - Suppression of the IgM Response by Aryl Hydrocarbon Receptor Activation in Human
      Primary B Cells Involves Impairment of Immunoglobulin Secretory Processes.
AB  - Aryl hydrocarbon receptor (AHR) activation by 2, 3, 7, 8-tetrachlorodibenzo-p
      dioxin (TCDD) is well established at suppressing humoral immunity. Previous
      studies in mouse B cells revealed that decreased IgM production was due to a
      significant suppression in the mRNA levels of the immunoglobulin M components
      (IgH, IgJ, and Igkappa chains) and subsequent decrease in IgM synthesis. In
      contrast, the current study shows that activation of AHR in human B cells also
      results in a significant suppression of the number of IgM-secreting cells, but
      this is not due to a decrease in the transcription or translation of IgH, IgJ,
      and Igkappa chains. Instead, the reduced humoral response is due to the
      impairment of IgM secretion. This is further evidenced by an accumulation of
      intracellular IgM in human B cells, which indicates that activation of AHR alters
      distinct regulatory pathways in human and mouse B cells leading to the suppressed
      primary IgM response. Collectively, these results demonstrate that although AHR
      activation mediates suppression of humoral immune responses across many different
      animal species, the mechanism of action is not necessarily conserved across
      species.

PMID- 29462423
TI  - Data-driven systems biology approaches.

PMID- 29462422
TI  - Multidrug Resistance Protein 1 Deficiency Promotes Doxorubicin-Induced Ovarian
      Toxicity in Female Mice.
AB  - Multidrug resistance protein 1 (MDR1), a phase III drug transporter that exports
      substrates out of cells, has been discovered in both cancerous and normal
      tissues. The over expression of MDR1 in cancer cells contributes to multiple drug
      resistance, whereas the MDR1 in normal tissues protects them from chemical
      induced toxicity. Currently, the role of MDR1 in the ovary has not been entirely
      understood. Our objective is to determine the function of MDR1 in protecting
      against chemotherapy-induced ovarian toxicity. Using both the in vivo transgenic
      mouse model and in vitro follicle culture model, we investigated the expression
      of MDR1 in the ovary, the effect of MDR1 deficiency on doxorubicin (DOX)-induced
      ovarian toxicity, and the ovarian steroid hormonal regulation of MDR1. Results
      showed that the MDR1 was expressed in the ovarian epithelial cells, stroma cells,
      theca cell layers, endothelial cells, and luteal cells. The lack of MDR1 did not
      affect female ovarian function and fertility; however, its deficiency
      significantly exacerbated the DOX-induced ovarian toxicity in both in vivo and in
      vitro models. The MDR1 showed significantly higher expression levels in the
      ovaries at estrus and metestrus stages than those at proestrus and diestrus
      stages. However, this dynamic expression pattern was not regulated by the ovarian
      steroid hormones of estrogen (E2) and progesterone (P4) but correlated to the
      number and status of corpus luteum. In conclusion, our study demonstrates that
      the lack of MDR1 promotes DOX-induced ovarian toxicity, suggesting the critical
      role of MDR1 in protecting female ovarian functions during chemotherapy.

PMID- 29462424
TI  - Seasonal Distribution and Container Preference Ratio of the Dengue Fever Vector
      (Aedes aegypti, Diptera: Culicidae) in Rawalpindi, Pakistan.
AB  - Aedes aegypti (L.) and Aedes albopictus (Skuse) are known vectors of dengue,
      chikungunya, and other pathogens; however, their ecology and role in virus
      transmission has not been well studied in Pakistan. Here, we report on an
      intensive survey of potential breeding sites of Ae. aegypti in Rawalpindi, Punjab
      Province, Pakistan. The study continued for 11 mo and was divided into three
      seasons: January to June (pre-monsoon), July to September (monsoon), and October
      November (post-monsoon). Larval mosquitoes were collected from all wet containers
      present in and around the houses. Altogether 5,570,418, 2,930,508, and 1,507,111
      water-filled containers were examined during each season, of which 2,703, 8,843,
      and 3,439 were found positive for Ae. aegypti larvae or pupae, yielding Breteau
      indices of 0.46, 2.92, and 1.99%, respectively. Among 14 container types
      examined, the breeding preference ratio during all seasons was highest for roof
      top water tanks and room evaporative coolers, followed by discarded tires and
      urban trash. The study concluded that increased urbanization, insufficient water
      supply and inefficient removal of urban trash resulted in increased numbers of
      nonbiodegradable containers around human dwellings, thereby creating ideal
      breeding habitats for Ae. aegypti. Measures such as integrated vector management,
      minimization of the breeding potential of Ae. aegypti by water management, proper
      disposal of discarded tires and urban trash, and health education were
      recommended for control of Ae. aegypti.

PMID- 29462425
TI  - Chitosan-adjuvanted Mycoplasma gallisepticum bacterin via intraocular
      administration enhances Mycoplasma gallisepticum protection in commercial layers.
AB  - Mycoplasma gallisepticum (MG) causes respiratory signs and economic losses in the
      poultry industry. MG vaccination is one of the effective prevention and control
      measures that have been used around the world. Our previous study demonstrated
      that chitosan-adjuvanted MG bacterin could effectively reduce pathological
      lesions induced by MG and that chitosan could be used as an adjuvant in MG
      bacterin. The present study determining the efficacy of MG bacterins against the
      Thai MG strain was based on vaccine programs. Seven groups (25 layers/group) were
      received MG bacterins containing 0.5% chitosan or a commercial bacterin via
      intramuscular (IM) or intraocular (IO) route at 6 and 10 wk of age. Sham-negative
      and sham-positive controls were groups 1 and 2, respectively. Group 3: IM route
      of chitosan bacterin followed by IM route of chitosan bacterin; group 4:
      commercial bacterin via IM route followed by chitosan bacterin via IO route;
      group 5: commercial bacterin via IM route followed by commercial bacterin via IM
      route; group 6: chitosan bacterin via IM followed by chitosan bacterin via IO
      route; and group 7: chitosan bacterin via IO route followed by chitosan bacterin
      via IO route were determined. At 16 wk of age, all groups, excluding group 1,
      were challenged intratracheally with 0.1 mL containing Thai MG strain 107 colony
      forming unit. At 17, 18, and 20 wk of age, 5 birds in each group were bled for
      serological testing and swabbed at the choanal cleft for the quantitative real
      time PCR assay, the euthanized and necropsied. The results showed that birds
      vaccinated with a commercial intramuscular bacterin followed by an intraocularly
      chitosan adjuvant bacterin showed the best protection against the MG challenge.
      The study indicated that chitosan could be the effective mucosal adjuvant and
      increased the effectiveness of MG bacterin.

PMID- 29462426
TI  - Arabidopsis BRASSINOSTEROID INACTIVATOR2 is a typical BAHD acyltransferase
      involved in brassinosteroid homeostasis.
AB  - Brassinosteroids (BRs) are plant-specific steroidal hormones; BR homeostasis is
      crucial for various aspects of plant growth and development. However, to date,
      the BR inactivation process has not been thoroughly elucidated. In this study, we
      identified and characterized a novel BAHD family acyltransferase gene,
      BRASSINOSTEROID INACTIVATOR2 (BIA2), involved in BR inactivation. BIA2
      overexpressing (OE-BIA2) plants displayed typical BR-deficient phenotypes, which
      were rescued by exogenous BR treatment. Real-time qRT-PCR and transcriptome
      analyses showed that expression levels of virtually all of the BR biosynthetic
      genes were increased, whereas the expression of many BR inactivation genes was
      reduced in OE-BIA2 plants. Root inhibition assays showed that the root growth of
      OE-BIA2 plants was inhibited. We obtained plants with an intermediate phenotype
      by crossing the OE-BIA2 plants with BRASSINOSTEROID-INSENSITIVE1 (BRI1)
      overexpressing plants. The null BIA2 mutants had longer hypocotyls in the dark.
      BIA2 was predominantly expressed in roots, and its expression was induced by 24
      epibrassinolide or dark treatment, but it exhibited a differential expression
      pattern compared with its homologue, BIA1. Furthermore, genetic transformation
      with point-mutant and deleted-BIA2 constructs confirmed that the HXXXD motif is
      essential for the function of BIA2. Taken together, these findings indicate that
      BIA2 is a typical BAHD acyltransferase that is involved in BR homeostasis and may
      inactivate bioactive BRs by esterification, particularly in roots and hypocotyls
      under dark conditions.

PMID- 29462427
TI  - Effects of terrestrial runoff on the coral communities in Santiago Bay, Colima,
      Mexican Pacific Coast.
AB  - Coral reef ecosystems are under stress of different origins, from factors
      including sedimentation, fragmentation, overfishing, and tourism, depending on
      their geographical location, depth, and proximity to recreation areas. In this
      study of Juluapan Lagoon, we examined the relationship between various water
      quality attributes and the status indicators of the coral community at La Boquita
      reef. During 2011 (12 months of sampling), six monitoring stations in the
      Juluapan lagoon were established in order to observe the gradient of the
      distribution of the physicochemical parameters: three stations on the upper part,
      or BI, (S4 to S6) and three more in the lower part, or BII, (S1 to S3). A control
      station (CS) was located in the coral reef close to the lagoon channel, and where
      dissolved inorganic nutrients and cellular carbon content were determined.
      Additionally, we considered the monitoring of three of the eight largest coral
      structures/headlands of this community: the first was the station closest to the
      channel communicating with Juluapan lagoon (C1), the second was in the
      intermediate region with respect to that lagoon (C2), and the third was farthest
      from the channel (C3). Three line intercept transects (LIT) 30 m in length and
      perpendicular to the coast provenance were established in each station, and the
      parameters indicative of the status of corals were evaluated in an area of 60 m2
      on each transect (180 m2 by the station). Turbidity, evidence of fishing, signs
      of settling, algal coverage, abundance of fish, rate of sediment, and coral
      health records (as for CoralWach chart) were determined in situ and from digital
      photographs and videos. Considering various community status indicators used in
      the reef area, we could recognize a state of general deterioration, which was
      reflected in the loss of 17 % of coral coverage. The main anthropogenic
      disturbances in adjacent areas to La Boquita reef included wastewater discharges
      into the lagoon, tourist developments in the coastal zone, deforestation and
      erosion resulting from inappropriate development, and the runoff of nutrients
      from agricultural lands nearby the lagoon. All these significantly contributed to
      the nutrient-enriched waters of the lagoon, especially in summer, with negative
      effects on the coral community. Continued exposure to these factors, coupled with
      the lack of control over other anthropogenic components, has promoted the
      maintenance of a chronic stress state in the studied coral community. Our
      findings highlight the need for the development of appropriate coastal management
      and conservation policies for the coral reefs of the Mexican Pacific Coast.

PMID- 29462428
TI  - Gene mutation and micronucleus assays in gpt delta mice treated with 2,2',4,4'
      tetrabromodiphenyl ether.
AB  - Flame retardant polybrominated diphenyl ethers (PBDEs) are a class of persistent
      organic pollutants (POPs). 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is a
      representative PBDE congener with widespread distribution and relatively high
      toxicity potential. Although it has been reported that BDE-47 can cause DNA
      damage in various in vitro systems, few studies have provided in vivo
      genotoxicity information. The aim of the present study was to investigate the
      genotoxicity of BDE-47 in mice. Male gpt delta mice were administered BDE-47 by
      gavage at 0, 0.0015, 1.5, 10 and 30 mg/kg/day, and 6 days per week for six
      consecutive weeks. Before the first treatment, and at 2.5 and 5 weeks after the
      first treatment, peripheral blood was collected from tails and the micronucleus
      assay and the Pig-a gene mutation assay were performed. After the last treatment,
      the mutant frequencies of the gpt gene in the liver and the germ cells from
      seminiferous tubules were determined. All these assays failed to produce positive
      results, suggesting that BDE-47 was neither clastogenic nor mutagenic in both
      target and non-target tissues in gpt delta mice.

PMID- 29462429
TI  - A glycomics approach to discover novel renal biomarkers in birds by
      administration of cisplatin and diclofenac to chickens.
AB  - Avian species have a unique renal structure and abundant blood flow into the
      kidneys. Although many birds die due to nephrotoxicity caused by chemicals, there
      are no early biomarkers for renal lesions. Uric acid level in blood, which is
      generally used as a renal biomarker, is altered when the kidney function is
      damaged by over 70%. Therefore, early biomarkers for kidney injury in birds are
      needed. In humans, glycomics has been at the forefront of biological and medical
      sciences, and glycans are used as biomarkers of diseases, such as carcinoma. In
      this study, a glycomics approach was used to screen for renal biomarkers in
      chicken. First, a chicken model of kidney damage was generated by injection of
      diclofenac or cisplatin, which cause acute interstitial nephritis (AIN) and acute
      tubular necrosis (ATN), respectively. The nephrotoxicity levels were determined
      by a blood chemical test and histopathological analysis. The plasma N-glycans
      were then analyzed to discover renal biomarkers in birds. Levels of 14 glycans
      increased between pre- and post administration in kidney-damaged chickens in the
      diclofenac group, and some of these glycans had the same presumptive composition
      as those in human renal carcinoma patients. Glycan levels did not change
      remarkably in the cisplatin group. It is possible that there are changes in
      glycan expression due to AIN, but they do not reflect ATN. Although further
      research is needed in other species of birds, glycans are potentially useful
      biomarkers for AIN in avian species.

PMID- 29462430
TI  - Education and management of antimicrobials amongst nurses in Africa-a situation
      analysis: an Infection Control Africa Network (ICAN)/BSAC online survey.
AB  - Objectives: To assess the current involvement of nurses in the use and management
      of antimicrobials and their training in antimicrobial stewardship (AMS) across
      Africa. Methods: After a pilot study, an online questionnaire (SurveyMonkey) in
      both French and English was circulated via the Infection Control Africa Network
      (ICAN) mailing list to both members and non-members in Africa. The study was
      conducted from 26 May to 19 August 2016. Data were summarized in proportions and
      bar charts; proportions were compared using the chi2 test. A multivariate
      logistic regression model was built to identify independent factors associated
      with the practice of AMS. Results: While 96% of the 173 respondents were aware of
      the term 'AMS', 88.5% (146/165) undertook AMS tasks as part of their job; 91.9%
      (158/172) wanted to be more involved in AMS but 44.9% (71/158) reported there
      were barriers in doing so. AMS training was delivered to 36.7% (62/169) and 53.6%
      (90/168), respectively, during their undergraduate and postgraduate education.
      AMS training for healthcare workers in their institutions was reported by 50.3%
      (86/171), including training aimed at doctors (56.9%), pharmacists (76.7%),
      microbiologists (31.4%) and nurses (95.3%). However, 95.4% (164/172) of
      respondents asked for further education on AMS and the majority preferred AMS
      training to be part of the infection prevention curriculum (IPC) education. Three
      quarters of institutions had an AMS initiative, but only ~41% reported having
      seen a national AMS guideline. Conclusions: For Africa, we recommend AMS
      education at undergraduate level, AMS policies at institution and national levels
      and incorporating AMS training into the IPC for nurses.

PMID- 29462431
TI  - CONCENTRATION OF RADON IN DWELLINGS OF HEMAVATHI RIVER BASIN, KARNATAKA, INDIA.
AB  - Indoor radon, thoron and their progeny levels were measured in various types of
      dwellings during 2016-17 in Hemavathi river basin, Karnataka by using solid state
      nuclear track detector based pin-hole dosemeters; dwellings of various types were
      chosen for the measurement. The dosemeters containing the detector (LR-115, Type
      II Film) was used for this purpose. The concentration of indoor radon in the
      study area varied from 30.72 to 196.08 Bq m-3 with a median of 83.13 Bq m-3 and
      thoron concentration varied from 15.56 to 227.78 Bq m-3. Higher concentrations of
      radon and its progeny were observed in granite flooring and cement roofing
      dwellings compared to other types of dwellings. The reason for higher
      concentration of indoor radon and its progeny is due to activity of radium
      present in granite and provision of less ventilation in dwellings. The
      equilibrium equivalent radon, thoron concentrations and annual effective dose are
      discussed.

PMID- 29462432
TI  - Letter: Feasibility of Nucleus Accumbens Deep Brain Stimulation for Morbid,
      Treatment-Refractory Obesity.

PMID- 29462433
TI  - Congenital Cervical Spine Stenosis in a Multicenter Global Cohort of Patients
      With Degenerative Cervical Myelopathy: An Ambispective Report Based on a Magnetic
      Resonance Imaging Diagnostic Criterion.
AB  - BACKGROUND: Congenital spinal stenosis (CSS) of the cervical spine is a risk
      factor for acute spinal cord injury and development of degenerative cervical
      myelopathy (DCM). OBJECTIVE: To develop magnetic resonance imaging (MRI)-based
      criteria to diagnose preexisting CSS and evaluate differences between patients
      with and without CSS. METHODS: A secondary analysis of international
      prospectively collected data between 2005 and 2011 was conducted. We examined the
      data of 349 surgical DCM patients and 27 controls. Spinal canal and cord
      anteroposterior diameters were measured at noncompressed sites to calculate
      spinal cord occupation ratio (SCOR). Torg-Pavlov ratios and spinal canal
      diameters from radiographs were correlated with SCOR. Clinical and MRI factors
      were compared between patients with and without CSS. Surgical outcomes were also
      assessed. RESULTS: Calculation of SCOR was feasible in 311/349 patients. Twenty
      six patients with CSS were identified (8.4%). Patients with CSS were younger than
      patients without CSS (P = .03) and had worse baseline severity as measured by the
      modified Japanese Orthopedic Association score (P = .04), Nurick scale (P = .05),
      and Neck Disability Index (P < .01). CSS patients more commonly had T2 cord
      hyperintensity changes (P = .09, ns) and worse SF-36 Physical Component scores (P
      = .06, ns). SCOR correlated better with Torg-Pavlov ratio and spinal canal
      diameter at C3 than C5. Patients with SCOR >= 65% were also younger but did not
      differ in baseline severity. CONCLUSION: SCOR >= 70% is an effective criterion to
      diagnose CSS. CSS patients develop myelopathy at a younger age and have greater
      impairment and disability than other patients with DCM. Despite this, CSS
      patients have comparable duration of symptoms, MRI presentations, and surgical
      outcomes to DCM patients without CSS.

PMID- 29462434
TI  - Effects of in ovo injection of different doses of coccidiosis vaccine and turn
      out times on broiler performance,.
AB  - Inovocox EM1 vaccine (EM1) is hatchery-applied via in ovo injection for the
      control of coccidiosis in broiler chickens. Effects of 3 in ovo injection
      treatments (INT) and 2 turn-out times (TOT) on the hatching chick quality
      variables and 35 d posthatch performance of Ross * Ross 708 broilers were
      investigated. In a single-stage incubator, 1,440 hatching eggs were randomly
      distributed among 3 INT groups on each of 8 tray levels. At 19 d of incubation
      (doi), embryonated eggs were subjected to one of the following INT by in ovo
      injection: noninjected control; 1 * dose of EM1; 10 * dose of EM1. On 21 doi,
      hatchability of injected eggs (HI), hatching body weight (HBW), and hatching
      chick quality variables were determined. Additionally, for the grow-out phase,
      birds belonging to each INT were randomly subjected to a 7 or 10 d TOT. Twenty
      chicks were initially placed in each of 48 floor pens (6 INT * TOT combination
      groups * 8 replications) for growth performance evaluation from 0 to 35 d
      posthatch. The main effect of INT on hatching chick quality variables, as well as
      the main and interactive effects of INT and TOT on various grow-out performance
      variables were determined. Although there was no significant INT effect on HI or
      HBW, significant INT effects on chick total BW, yolk-free BW, and yolk sac weight
      were observed. There were significant INT effects on BWG and FCR in the 21- to 28
      d posthatch interval, as well as on BWG and FCR in the 0- to 35-d posthatch
      interval. There was no main effect of TOT or interactive effect of INT and TOT on
      BW and other performance variables from 0 to 35 d posthatch. There was a
      significant main effect of INT on relative intestine weight at 28 d posthatch. In
      conclusion, the injection of EM1 vaccine at a 10 * dose may affect hatching chick
      quality variables and growth performance up to 35 d posthatch.

PMID- 29462435
TI  - A Second Randomized Trial Comparing General Anesthesia to Conscious Sedation in
      Acute Ischemic Stroke Patients Undergoing Endovascular Treatment.

PMID- 29462436
TI  - A Sordid Affair: Spike Sorting and Data Reproducibility.

PMID- 29462437
TI  - Novel Autochthonous in vivo Model Identifies Genetic Drivers and Functional
      Suppressors in Glioblastoma.

PMID- 29462438
TI  - Targeting Epidermal Growth Factor Receptors in Recurrent Glioblastoma Via a Novel
      Epithelial Growth Factor Receptor-Conjugated Nanocell Doxorubicin Delivery
      System.

PMID- 29462439
TI  - Novel Photoconductive Material Demonstrates Potential for Dose Reduction in X-Ray
      Imaging.

PMID- 29462440
TI  - MeTro: A New Surgical Sealant.

PMID- 29462441
TI  - Regaining Consciousness: The Effect of Vagal Nerve Stimulation on a Patient in a
      Permanent Vegetative State.

PMID- 29462442
TI  - Seizing the Moment: A Randomized Trial of Surgery for Drug-Resistant Pediatric
      Epilepsy.

PMID- 29462443
TI  - Brainstem Hypoperfusion as the Inciting Factor in the Development of Essential
      Hypertension.

PMID- 29462445
TI  - Reply to comment 'Tabanus bovinus in Bolivia?' by Stephen M Smith.

PMID- 29462444
TI  - Business travel-associated illness: a GeoSentinel analysis.
AB  - Background: Analysis of a large cohort of business travelers will help clinicians
      focus on frequent and serious illnesses. We aimed to describe travel-related
      health problems in business travelers. Methods: GeoSentinel Surveillance Network
      consists of 64 travel and tropical medicine clinics in 29 countries; descriptive
      analysis was performed on ill business travelers, defined as persons traveling
      for work, evaluated after international travel 1 January 1997 through 31 December
      2014. Results: Among 12 203 business travelers seen 1997-2014 (14 045 eligible
      diagnoses), the majority (97%) were adults aged 20-64 years; most (74%) reported
      from Western Europe or North America; two-thirds were male. Most (86%) were
      outpatients. Fewer than half (45%) reported a pre-travel healthcare encounter.
      Frequent regions of exposure were sub-Saharan Africa (37%), Southeast Asia (15%)
      and South Central Asia (14%). The most frequent diagnoses were malaria (9%),
      acute unspecified diarrhea (8%), viral syndrome (6%), acute bacterial diarrhea
      (5%) and chronic diarrhea (4%). Species was reported for 973 (90%) of 1079
      patients with malaria, predominantly Plasmodium falciparum acquired in sub
      Saharan Africa. Of 584 (54%) with malaria chemoprophylaxis information, 92% took
      none or incomplete courses. Thirteen deaths were reported, over half of which
      were due to malaria; others succumbed to pneumonia, typhoid fever, rabies,
      melioidosis and pyogenic abscess. Conclusions: Diarrheal illness was a major
      cause of morbidity. Malaria contributed substantial morbidity and mortality,
      particularly among business travelers to sub-Saharan Africa. Underuse or non-use
      of chemoprophylaxis contributed to malaria cases. Deaths in business travelers
      could be reduced by improving adherence to malaria chemoprophylaxis and targeted
      vaccination for vaccine-preventable diseases. Pre-travel advice is indicated for
      business travelers and is currently under-utilized and needs improvement.

PMID- 29462447
TI  - Radiographic and Neurological Outcome After Surgical Treatment of Traumatic
      Fractures of the Ankylotic Thoracic Spine: A Retrospective Case Series.
AB  - BACKGROUND: Spontaneous thoracic ankylosis is a progressive degenerative process
      that predisposes patients to potentially highly unstable traumatic injuries.
      Acute hyperextension fractures result in dynamic instability putting the spinal
      cord at risk. OBJECTIVE: To describe preoperative radiographic characteristics of
      fractures of the ankylotic thoracic spine and relate findings to early
      postoperative radiographic and clinical outcomes. METHODS: A single center,
      retrospective review was performed of 28 surgically treated patients with
      fractures of the ankylotic thoracic spine. Radiographic assessment included
      preoperative fracture angulation (FA) and fracture displacement (FD), and
      postoperative change in sagittal alignment. Early clinical outcomes included
      preoperative and postoperative American Spinal Injury Association (ASIA) grade
      and perioperative complications. RESULTS: Seven patients (25%) presented with
      poor neurological grade (ASIA A-C) compared to 21 (75%) with good grade (ASIA D,
      E). At presentation, poor grade patients had a mean FA of 16.4 degrees  (range 0
      degrees -34.5 degrees ), and FD of 7.76 mm (range 0.8-9.2). Good grade patients
      had a mean FA of 18.2 degrees  (range 0 degrees -43.3 degrees ), and FD of 4.77
      mm (range 0-25.1). There was no statistically significant difference in FA or FD
      between groups (P = .70 and .20 respectively). All underwent posterior pedicle
      screw fixation for stabilization. Fifty per cent of patients presenting with ASIA
      C or D spinal cord injury improved 1 or more ASIA grades. There were no
      perioperative complications. Early postoperative sagittal alignment was
      maintained with a mean change of -2.6 degrees . CONCLUSION: Presenting fracture
      alignment does not significantly correlate with pre- or postoperative
      neurological status. Early posterior stabilization preserved neurological
      function, with neurological recovery occurring in a portion of individuals.

PMID- 29462446
TI  - Accuracy and Efficacy for Robotic Assistance in Implanting Responsive
      Neurostimulation Device Electrodes in Bilateral Mesial Temporal Lobe Epilepsy.
AB  - BACKGROUND: Responsive neurostimulation (RNS) is a relatively new treatment
      option that has been shown to be effective for patients with medically refractory
      focal epilepsy when resection is not possible, especially in bilateral mesial
      temporal onset. Robotic devices are becoming increasingly popular for use in
      stereotactic procedures such as stereoelectroencephalography, but have yet to be
      used when implanting RNS devices. OBJECTIVE: To show that these 2 forms of
      advanced technology were compatible and could be used effectively in patient
      care. METHODS: We implanted RNS devices in 3 patients with bilateral mesial
      temporal lobe epilepsy. Each patient was placed in the prone position, and
      electrode trajectories were planned via the robotic navigation system via a
      transoccipital approach. One lead was placed along each amygdalohippocampal
      complex. A small craniectomy was then created in the parietal region for RNS
      generator implantation. Actual and expected target locations and distance were
      calculated for each depth. There were no complications in this group. RESULTS:
      RNS devices with bilateral leads were successfully implanted in all 3 patients,
      with bilateral mesial temporal lobe onset. Follow-up ranged from 3 to 6 mo, and
      there were no complications in this group. The median distance between the
      estimate and actual targets was 2.18 (range = 1.11-3.27) mm. CONCLUSION: We show
      that implanting RNS devices with robotic assistance is feasible with excellent
      precision and accuracy. The advantages of using robotic assistance include higher
      flexibility, accuracy, precision, and consistency.

PMID- 29462448
TI  - Spinal Cord Suspension Using Dentate Ligament Hitch Stitches: A Novel Technique
      for the Repair of Ventral Spinal Cord Herniation.
AB  - BACKGROUND: Idiopathic spinal cord herniation is usually repaired by releasing
      the spinal cord and inserting a dural patch to close the herniated segment of
      dura. However, reherniation is a potential limitation of this standard technique.
      OBJECTIVE: To describe early results of a novel technique that utilizes the
      dentate ligament to hitch the spinal cord and prevent reherniation. METHODS: Two
      patients underwent dural hernia repair and the dentate hitch technique was
      performed. RESULTS: Restored lower limb power and mobility, and satisfactory
      reduction of spinal cord herniation on magnetic resonance imaging in 2 patients
      at 6- and 24-mo follow-ups, respectively. CONCLUSION: The dentate hitch technique
      can achieve repair of spinal cord herniation, with satisfactory postoperative
      results and minimizes the risk of reherniation.

PMID- 29462449
TI  - Endoscopic Transorbital Superior Eyelid Approach for the Management of Selected
      Spheno-orbital Meningiomas: Preliminary Experience.
AB  - BACKGROUND: Feasibility and safety of spheno-orbital meningioma resection by
      means of endoscopic-assisted transorbital route. OBJECTIVE: To evaluate the
      feasibility and outcomes of the transorbital endoscopic management of selected
      spheno-orbital meningiomas. As secondary aims, symptom improvement and tumor
      volume removed were evaluated. METHODS: Retrospective chart evaluation of
      patients with spheno-orbital meningiomas treated by means of endoscopic
      transorbital superior eyelid approach in 3 referral centers over the last 4 yr.
      RESULTS: Fourteen cases were included in this study. In 4 patients, the
      transorbital endoscopic approach was combined with an endonasal route. Mean age
      was 51 and male-to-female ratio was 1:6. In 8 patients (57.1%), an intraorbital
      involvement was observed, 3 of them (21.4%) showed significant intraconal
      disease. No patient presented significant cavernous sinus infiltration. Main
      presenting symptoms were proptosis, diplopia, and visual impairment in 14, 6, and
      6 patients, respectively. Mean proptosis improvement was 2 mm (standard deviation
      2.3). We observed no major postoperative complications. CONCLUSION: Our
      preliminary clinical experience seems to demonstrate that selected spheno-orbital
      meningiomas can be safely managed by means of an endoscopic transorbital route
      through a superior eyelid approach. Patients with orbital or cavernous sinus
      infiltration are at highest risk of persistence.

PMID- 29462450
TI  - False-Positive and False-Negative Results of Motor Evoked Potential Monitoring
      During Surgery for Intramedullary Spinal Cord Tumors.
AB  - BACKGROUND: Motor evoked potential (MEP) recording is used as a method to monitor
      integrity of the motor system during surgery for intramedullary tumors (IMTs).
      Reliable sensitivity of the monitoring in predicting functional deterioration has
      been reported. However, we observed false positives and false negatives in our
      experience of 250 surgeries of IMTs. OBJECTIVE: To delineate specificity and
      sensitivity of MEP monitoring and to elucidate its limitations and usefulness.
      METHODS: From 2008 to 2011, 58 patients underwent 62 surgeries for IMTs. MEP
      monitoring was performed in 59 operations using transcranial electrical
      stimulation. Correlation with changes in muscle strength and locomotion was
      analyzed. A group undergoing clipping for unruptured aneurysms was compared for
      elicitation of MEP. RESULTS: Of 212 muscles monitored in the 59 operations, MEP
      was recorded in 150 (71%). Positive MEP warnings, defined as amplitude decrease
      below 20% of the initial level, occurred in 37 muscles, but 22 of these (59%) did
      not have postoperative weakness (false positive). Positive predictive value was
      limited to 0.41. Of 113 muscles with no MEP warnings, 8 muscles developed
      postoperative weakness (false negative, 7%). Negative predictive value was 0.93.
      MEP responses were not elicited in 58 muscles (27%). By contrast, during clipping
      for unruptured aneurysms, MEP was recorded in 216 of 222 muscles (96%).
      CONCLUSION: MEP monitoring has a limitation in predicting postoperative weakness
      in surgery for IMTs. False-positive and false-negative indices were abundant,
      with sensitivity and specificity of 0.65 and 0.83 in predicting postoperative
      weakness.

PMID- 29462451
TI  - Transsylvian Transuncal Approach for an Anterior Midbrain Cavernous Malformation
      Resection: A Case Report.
AB  - BACKGROUND AND IMPORTANCE: Cavernous malformations (CMs) are vascular
      abnormalities with a hemorrhage risk of 0.2% to 5% per year, according to their
      location. Brainstem CMs seem to have a greater hemorrhagic risk and represent a
      neurosurgical challenge. We report here the first transsylvian transuncal (TS-TU)
      approach for an anteromedial mesencephalic CM resection. CLINICAL PRESENTATION: A
      29-yr-old female suddenly presented a left hemiparesis and central facial paresis
      with a diplopia in the upward gaze. A cerebral imagery revealed an 18-mm right
      cerebral peduncle CM with signs of acute hemorrhage. Two months later, she
      rebleed while pregnant. The pregnancy was interrupted. Five months later, a 3.0
      Tesla magnetic resonance imaging (MRI) with diffusion tensor imaging sequences
      was realized for preoperative planning followed by a gross total resection of the
      CM through a TS-TU approach to avoid the perforating arteries of the anterior
      perforated substance. The patient presented postoperatively again a left
      hemiparesis and central facial paresis with a right oculomotor nerve paresis. On
      the tenth postsurgical day, she developed a Holmes' tremor of the left upper
      limb, for which a Levodopa treatment was initiated. Three months postoperative,
      MRI showed a gross total resection of the mesencephalic CM without complications.
      A complete clinical recovery was observed 1 yr later. CONCLUSION: We describe
      here the first performance of a TS-TU approach for an anterior mesencephalic CM
      resection. This surgical approach allowed direct access to the CM, avoiding the
      vascularization of the anterior perforated substance.

PMID- 29462453
TI  - Minimally Invasive Surgical Approach to Filum Sectioning: Technical Note.

PMID- 29462452
TI  - Microsurgical Resection of a Type 1 Spinal Dural Arteriovenous Fistula: A 3
      Dimensional Operative Video.

PMID- 29462454
TI  - Anatomic Investigation of the Trajectory for Stereotactic Laser
      Amygdalohippocampectomy.

PMID- 29462457
TI  - Erratum to: Devoe DJ, Peterson A, Addington J. Negative Symptom Interventions in
      Youth at Risk of Psychosis: A Systematic Review and Network Meta-Analysis.

PMID- 29462455
TI  - Systemic Biomarkers of Accelerated Aging in Schizophrenia: A Critical Review and
      Future Directions.
AB  - BACKGROUND: Schizophrenia is associated with increased physical morbidity and
      early mortality, suggesting that the aging process may be accelerated in
      schizophrenia. However, the biological underpinnings of these alterations in
      aging in schizophrenia are unclear. METHOD: We conducted a detailed search of
      peer-reviewed empirical studies to evaluate evidence for accelerated biological
      aging in schizophrenia based on systemic, age-related biomarkers. We included
      studies that investigated differences between persons with schizophrenia and
      healthy comparison subjects in levels of biomarkers known to be associated with
      aging and examined the relationship of these biomarkers to age in the 2 groups.
      RESULTS: Forty-two articles that met our selection criteria were reviewed. Nearly
      75% reported abnormal biomarker levels among individuals with schizophrenia,
      including indices of inflammation, cytotoxicity, oxidative stress, metabolic
      health, gene expression, and receptor/synaptic function, with medium to large
      effect sizes reported in many studies. Twenty-nine percent of the studies
      observed differential age-related decline in schizophrenia. Markers of
      receptor/synaptic function and gene expression were most frequently
      differentially related to age in schizophrenia. Schizophrenia patients with
      greater disease severity and longer illness duration exhibited higher levels of
      inflammatory and oxidative stress biomarkers and shorter telomere length.
      CONCLUSIONS: Most studies show biomarker abnormalities in schizophrenia, and
      there is some suggestion for accelerated aging. Although definitive
      interpretation is limited by cross-sectional design of the published reports,
      findings in the area of gene expression and synaptic function are promising and
      pave the way for future longitudinal studies needed to fully test this
      hypothesis.

PMID- 29462456
TI  - N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward
      Biomarker-Guided Treatment in Early Psychosis.
AB  - Biomarker-guided treatments are needed in psychiatry, and previous data suggest
      oxidative stress may be a target in schizophrenia. A previous add-on trial with
      the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in
      chronic patients. We aim to study NAC's impact on symptoms and neurocognition in
      early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could
      represent valid biomarkers to guide treatment. In a double-blind, randomized,
      placebo-controlled trial in 63 EP patients, we assessed the effect of NAC
      supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox
      markers (brain GSH [GSHmPFC], blood cells GSH levels [GSHBC], GSH peroxidase
      activity [GPxBC]). No changes in negative or positive symptoms or functional
      outcome were observed with NAC, but significant improvements were found in favor
      of NAC on neurocognition (processing speed). NAC also led to increases of GSHmPFC
      by 23% (P = .005) and GSHBC by 19% (P = .05). In patients with high-baseline
      GPxBC compared to low-baseline GPxBC, subgroup explorations revealed a link
      between changes of positive symptoms and changes of redox status with NAC. In
      conclusion, NAC supplementation in a limited sample of EP patients did not
      improve negative symptoms, which were at modest baseline levels. However, NAC led
      to some neurocognitive improvements and an increase in brain GSH levels,
      indicating good target engagement. Blood GPx activity, a redox peripheral index
      associated with brain GSH levels, could help identify a subgroup of patients who
      improve their positive symptoms with NAC. Thus, future trials with antioxidants
      in EP should consider biomarker-guided treatment.

PMID- 29462458
TI  - m-AAA Complexes Are Not Crucial for the Survival of Arabidopsis Under Optimal
      Growth Conditions Despite Their Importance for Mitochondrial Translation.
AB  - For optimal mitochondrial activity, the mitochondrial proteome must be properly
      maintained or altered in response to developmental and environmental stimuli.
      Based on studies of yeast and humans, one of the key players in this control are
      m-AAA proteases, mitochondrial inner membrane-bound ATP-dependent metalloenzymes.
      This study focuses on the importance of m-AAA proteases in plant mitochondria,
      providing their first experimentally proven physiological substrate. We found
      that the Arabidopsis m- AAA complexes composed of AtFTSH3 and/or AtFTSH10 are
      involved in the proteolytic maturation of ribosomal subunit L32. Consequently, in
      the double Arabidopsis ftsh3/10 mutant, mitoribosome biogenesis, mitochondrial
      translation and functionality of OXPHOS (oxidative phosphorylation) complexes are
      impaired. However, in contrast to their mammalian or yeast counterparts, plant m
      AAA complexes are not critical for the survival of Arabidopsis under optimal
      conditions; ftsh3/10 plants are only slightly smaller in size at the early
      developmental stage compared with plants containing m-AAA complexes. Our data
      suggest that a lack of significant visible morphological alterations under
      optimal growth conditions involves mechanisms which rely on existing functional
      redundancy and induced functional compensation in Arabidopsis mitochondria.

PMID- 29462459
TI  - Evidence that Myotis lucifugus "Subspecies" are Five Nonsister Species, Despite
      Gene Flow.
AB  - While genetic exchange between nonsister species was traditionally considered to
      be rare in mammals, analyses of molecular data in multiple systems suggest that
      it may be common. Interspecific gene flow, if present, is problematic for
      phylogenetic inference, particularly for analyses near the species level. Here,
      we explore how to detect and account for gene flow during phylogeny estimation
      using data from a clade of North American Myotis bats where previous results have
      led researchers to suspect that gene flow among lineages is present. Initial
      estimates of phylogenetic networks and species trees indicate that subspecies
      described within Myotis lucifugus are paraphyletic. In order to explore the
      extent to which gene flow is likely to interfere with phylogeny estimation, we
      use posterior predictive simulation and a novel Approximate Bayesian Computation
      approach based on gene tree distances. The former indicates that the species tree
      model is a poor fit to the data, and the latter provides evidence that a species
      tree with gene flow is a better fit. Taken together, we present evidence that the
      currently recognized M. lucifugus subspecies are paraphyletic, exchange alleles
      with other Myotis species in regions of secondary contact, and should be
      considered independent evolutionary lineages despite their morphological
      similarity.

PMID- 29462460
TI  - An interview with Professor Bert O' Malley.

PMID- 29462461
TI  - Identification and characterization of the proteins in broth of stewed
      traditional Chinese yellow-feathered chickens.
AB  - Soups and broths are popular in the world due to their nutrition and flavor, and
      flavor compounds tend to be bound by the proteins in the soups and broth,
      influencing the flavor perception. Thus, identification of the major proteins in
      meat-based broth may present a basis for understanding protein adsorption of
      flavor compounds. The present study aimed to identify the major proteins in
      traditional Chinese chicken broth and to describe the structural changes of
      proteins during stewing (1, 2, or 3 h). As stewing time increased, protein
      content in the broth significantly increased. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) indicated that the macro-molecule
      proteins (>10 kDa) in the broth were mainly gelatin and actin and that the micro
      molecule proteins fractions (<10 kDa) increased substantially. The gelatin had an
      ordered structure even after 3 h of stewing, as seen by circular dichroism (CD)
      spectroscopy. The presence of reactive sulfhydryl groups increased remarkably
      with stewing time. The surface hydrophobicity of the proteins significantly
      increased within 2 h then deceased slightly after 3 h. The intermolecular
      crosslinks, as indicated by dispersion index, increased remarkably, consistent
      with the result of atomic force microscopy (AFM), which together suggested that
      protein aggregation increased during stewing. These findings suggested that
      gelatin was the structural protein in the broth system and that intermolecular
      crosslinks functioned to maintain the broth system.

PMID- 29462462
TI  - Effects of supplementation with alpha-tocopherol, ascorbic acid, selenium, or
      their combination in linseed oil-enriched diets on the oxidative status in
      broilers.
AB  - A trial was conducted to investigate whether, and if so to what extent, the
      combined supplementation of vitamin E, vitamin C, and selenium was superior to
      their sole supplementation concerning the oxidative stress induced by a high n-3
      dietary polyunsaturated fatty acids (PUFA) intake in broilers. Four hundred 21
      day-old Ross 308 male broilers were allocated to 5 experimental groups fed the
      following linseed oil (5%)-enriched finisher diets: Cont (no supplement), +E (200
      IU vitamin E/kg feed), +C (250 mg vitamin C/kg feed), +Se (0.2 mg selenium/kg
      feed), or +ECSe (concentrations as in the sole supplementation, combined).
      Analyses of malondialdehyde (MDA), vitamin C, and alpha- and gamma-tocopherols in
      plasma, antioxidant capacity of water- (ACW) and lipid- (ACL) soluble compounds
      in serum, and glutathione peroxidase (GPx) and superoxide dismutase (SOD)
      activities in whole blood were performed. In breast muscle, analyses of MDA,
      alpha- and gamma-tocopherols, ACW, selenium, and fatty acid (FA) composition were
      carried out. Birds fed the combination of antioxidants showed reduced average
      daily gain (ADG) and average daily feed intake (ADFI) and, as +E, lower MDA and
      gamma-tocopherol, together with raised alpha- tocopherol levels in plasma and
      lower MDA and raised alpha- tocopherol levels in breast muscle compared to the
      control. The combination of antioxidants in the +ECSe group raised GPx activity
      in whole blood compared to the control. In conclusion, results indicated that
      vitamin E is the most effective antioxidant to alleviate oxidative stress caused
      by high dietary PUFA and that the supplementation with additional vitamin C and
      selenium did not have clear synergistic effect.

PMID- 29462464
TI  - Determining Brain Mechanisms that Underpin Analgesia Induced by the Use of Pain
      Coping Skills.
AB  - Objective: Cognitive behavioral therapies decrease pain and improve mood and
      function in people with osteoarthritis. This study assessed the effects of coping
      strategies on the central processing of knee pain in people with osteoarthritis
      of the knees. Methods: Mechanical pressure was applied to exacerbate knee pain in
      28 people with osteoarthritis of the knee. Reports of pain intensity and
      functional magnetic resonance imaging measures of pain-related brain activity
      were recorded with and without the concurrent use of pain coping skills. Results:
      Coping skills led to a significant reduction in pain report (Coping = 2.64 +/-
      0.17, Not Coping = 3.28 +/- 0.15, P < 0.001). These strategies were associated
      with increased activation in pain modulatory regions of the brain (medial
      prefrontal and rostral anterior cingulate cortices, Pcorrected < 0.05) and
      decreased pain-related activation in regions that process noxious input
      (midcingulate cortex, supplementary motor area, secondary somatosensory cortex,
      and anterior parietal lobule, Pcorrected < 0.05). The magnitude of the decrease
      in pain report during the use of pain coping strategies was found to be
      proportional to the decrease in pain-related activation in brain regions that
      code the aversive/emotional dimension of pain (anterior insula, inferior frontal
      gyrus, orbitofrontal cortex, Pcorrected < 0.05) but did not differ between groups
      with and without training in coping skills. However, training in coping skills
      reduced the extent to which brain responses to noxious input were influenced by
      anxiety. Conclusions: The results of this study support previous reports of pain
      modulation by cognitive pain coping strategies and contribute to the current
      understanding of how analgesia associated with the use of pain coping strategies
      is represented in the brain.

PMID- 29462463
TI  - TYPLEX(r) Chelate, a novel feed additive, inhibits Campylobacter jejuni biofilm
      formation and cecal colonization in broiler chickens.
AB  - Reducing Campylobacter spp. carriage in poultry is challenging, but essential to
      control this major cause of human bacterial gastroenteritis worldwide. Although
      much is known about the mechanisms and route of Campylobacter spp. colonization
      in poultry, the literature is scarce on antibiotic-free solutions to combat
      Campylobacter spp. colonization in poultry. In vitro and in vivo studies were
      conducted to investigate the role of TYPLEX(r) Chelate (ferric tyrosine), a novel
      feed additive, in inhibiting Campylobacter jejuni (C. jejuni) biofilm formation
      and reducing C. jejuni and Escherichia coli (E. coli) colonization in broiler
      chickens at market age. In an in vitro study, the inhibitory effect on C. jejuni
      biofilm formation using a plastic bead assay was investigated. The results
      demonstrated that TYPLEX(r) Chelate significantly reduces biofilm formation. In
      an in vivo study, 800 broilers (one d old) were randomly allocated to 4 dietary
      treatments in a randomized block design, each having 10 replicate pens with 20
      birds per pen. At d 21, all birds were challenged with C. jejuni via seeded
      litter. At d 42, cecal samples were collected and tested for volatile fatty acid
      (VFA) concentrations and C. jejuni and E. coli counts. The results showed that
      TYPLEX(r) Chelate reduced the carriage of C. jejuni and E. coli in poultry by 2
      and 1 log10 per gram cecal sample, respectively, and increased cecal VFA
      concentrations. These findings support TYPLEX(r) Chelate as a novel non
      antibiotic feed additive that may help produce poultry with a lower public health
      risk of Campylobacteriosis.

PMID- 29462465
TI  - Corrigendum: Blue light-dependent changes in loosely bound calcium in Arabidopsis
      mesophyll cells: an X-ray microanalysis study.

PMID- 29462466
TI  - Effect of pre-slaughter shackling and wing flapping on plasma parameters,
      postmortem metabolism, AMPK, and meat quality of broilers.
AB  - The objective of this study was to determine the effects of shackling and wing
      flapping on stress, postmortem metabolism, AMP-activated protein kinase (AMPK),
      and quality of broiler pectoralis major. Before slaughter, a total of 80 Arbor
      Acres broilers was randomly categorized into 2 replicate pens (40 broilers per
      pen) and each pen randomly divided into 2 groups (shackling, T; control, C).
      Corticosterone, creatine kinase, and lactate dehydrogenase were determined on
      blood plasma parameters. Pectoralis major were removed after evisceration and
      used for determination of energy metabolism, meat quality, and AMPK
      phosphorylation. In this study, shackling and wing flapping increased (P < 0.05)
      plasma corticosterone level, creatine kinase activity, and lactate dehydrogenase
      activity. Shackling and wing flapping increased (P < 0.05) AMPKalpha(Thr172) and
      acetyl-CoA carboxylase (ACC) phosphorylation, followed by rapid glycolysis and
      accumulation of lactic acid, and leading to a fast pH decline in the initial
      postmortem meat. Shackling and wing flapping have an adverse effect on final meat
      quality, which increased (P < 0.05) muscle lightness, drip loss, and cooking
      loss. The results indicate that antemortem shackling and wing flapping increased
      stress and AMPKalpha(Thr172) phosphorylation, which may accelerate glycolysis and
      lead to a low water-holding capacity of broiler meat.

PMID- 29462467
TI  - Secundum Atrial Septal Defect.

PMID- 29462468
TI  - The impact of vitamin D status and parameters of calcium metabolism in patients
      with primary hyperparathyroidism.
AB  - Background: There is ample evidence associating vitamin D deficiency in primary
      hyperparathyroidism (PHP) patients with more severe disease manifestations and
      increased risk of postoperative hypocalcemia. Yet, there is limited data
      regarding the safety of vitamin D repletion in these patients. Aim: To assess the
      safety of vitamin D repletion in PHP patients in a real-world setting. Design: We
      included patients with asymptomatic PHP and few symptomatic patients who declined
      surgery, followed in our clinic, and treated on a routine basis with 2000 IU/day
      of vitamin D3. Methods: Serum calcium (sCa), PTH, 25-hydroxyvitamin D, and 24 h
      urinary calcium (uCa) and creatinine collections were compared between the lowest
      and the highest vitamin D time points. Results: There were 40 patients of a mean
      age was 63 +/- 10 years. 25(OH)D at lowest and highest vitamin D time points was
      15.5 +/- 6.2 ng/ml and 33.2 +/- 8, respectively (P < 0.001). Serum calcium was
      not affected by the changes in vitamin D levels. In none of the patients did sCa
      exceed 11.5 mg/dL. uCa was 220 +/- 110 mg/24 h at the lowest vitamin D time point
      and 260 +/- 140 at the highest vitamin D time point (P = 0.14). uCa exceeded 400
      mg/24 h in two vs. five patients (P = 0.23) at the lowest and highest vitamin D
      time points, respectively. PTH was not significantly different between the
      different vitamin D time points. Discussion/Conclusion: Vitamin D repletion in
      PHP seems safe. Considering the documented adverse influence of vitamin D
      deficiency in PHP, particularly on skeletal manifestations and on the
      postoperative course, vitamin D repletion is warranted.

PMID- 29462469
TI  - Torture-if it doesn't work-why use it?

PMID- 29462470
TI  - Can prediction models in primary care enable earlier diagnosis of rare rheumatic
      diseases?

PMID- 29462471
TI  - The use of panoramic radiographs to decide when interceptive extraction is
      beneficial in children with palatally displaced canines based on a randomized
      clinical trial.
AB  - Objective: To evaluate which palatally displaced canines (PDCs) benefit from
      interceptive extraction of the deciduous canine, to assess possible side effects
      from the extraction, and to analyse other dental deviations in patients with
      PDCs. Design, settings, participants, and intervention: A sample of 67 patients
      (40 girls, mean age: 11.3 +/- 1.1; 27 boys, mean age +/- SD: 11.4 +/- 0.9) with
      unilateral (45) or bilateral (22) PDCs were consecutively recruited and randomly
      allocated to extraction or non-extraction using block randomization. No patients
      dropped out after randomization or during the study. The patients were given a
      clinical examination and panoramic radiographs were taken at baseline and after 6
      (T1) and 12 months (T2). An individual therapy plan was made for the PDCs that
      had not erupted at T2. Measurements were performed blindly and the outcome
      measures were: canine position and angulation, root development, midline shift,
      rotation, or movement of adjacent teeth into the extraction site, and frequency
      of other dental deviations. Results: Interceptive deciduous canine extraction is
      beneficial if the alpha angle is between 20 and 30 degrees. A PDC located in
      sector 4 with an alpha angle >30 degrees should have immediate surgical exposure,
      while canines angulated less than 20 degrees and located in sector 2 can be
      observed without prior interceptive extraction. Deciduous canine extraction was
      more beneficial in younger patients with less advanced root development. Minor
      side effects, such as rotation or migration of teeth into the extraction space,
      were observed in 15 out of 35 patients. A majority of the patients had other
      dental deviations than PDC in the dentition. Limitations: The results are only
      valid for patients with no space deficiency in the maxilla and with PDCs located
      in sector 2-4. Harms: No harms were detected. Conclusions: The alpha angle and
      sector position are good diagnostic predictors of when interceptive extraction is
      beneficial. Minor side effects are seen after the extraction and the majority of
      the patients had other dental deviations too. Registration: This trial was
      registered at http://www.fou.nu/is/sverige, registration number: 211141.

PMID- 29462472
TI  - Functionally Diversified Members of the MIR165/6 Gene Family Regulate Ovule
      Morphogenesis in Arabidopsis thaliana.
AB  - The ovules of flowering plants consist of a central embryo sac and surrounding
      layers of the inner and outer integument. As these structural units eventually
      give rise to the embryo/endosperm and seed coat, respectively, a precisely
      organized ovule structure is essential for successful fertilization and seed
      production. In Arabidopsis thaliana, correct ovule patterning depends on the
      restricted expression of the CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIP III)
      gene PHABULOSA (PHB) in the apical region of the incipient inner integument,
      which in turn is regulated via post-transcriptional suppression by miR165 and
      miR166 (miR165/6) derived from multiple MIR165/6 genes. While a common subset of
      MIR165/6 genes regulate PHB expression in the root meristem, leaf primordium and
      embryo, it is unknown whether the same MIR165/6 subset also regulate PHB
      expression during ovule development. Furthermore, it is unclear where in the
      ovule primordia miR165/6 are produced. Here, we show that a distinct set of
      MIR165/6 genes that are highly expressed in the small regions of early ovule
      primordia restrict the PHB expression domain to promote integument formation.
      MIR165/6 genes that function in ovule development are phylogenetically distinct
      from those acting in roots and leaf primordia. Taken together, our data suggest
      that members of the MIR165/6 gene family are diversified in their expression
      capacity to establish elaborate PHB expression patterns depending on the
      developmental context, thereby allowing HD-ZIP III transcription factors to
      regulate multiple aspects of plant development.

PMID- 29462474
TI  - Acute steroid myopathy: a highly overlooked entity.
AB  - Background: Myopathy in patients being treated with corticosteroids is known
      primarily among chronically treated patients or in critically ill and
      mechanically ventilated patients receiving corticosteroids, often in high doses.
      Aim: To highlight the entity of acute, early onset corticosteroid-treatment
      associated myopathy and its characteristics. Design and Methods: Reporting our
      experience with four patients and reviewing all published reports of myopathy
      developing <=14 days of initiating corticosteroid-treatment. Results: Acute
      corticosteroid myopathy (ASM) exists, though the syndrome appears to be rare. It
      is characterized by unpredictability and heterogeneity, sometimes developing
      within 1-3 days, after a single dose, which may not be high and administered by
      varied routes. Proximal limb muscle weakness is the most common form, but distal
      limb, bulbar and respiratory muscles may be involved. Steroid cessation often
      leads to improvement/resolution, but irreversibility may occur. Conclusions: A
      high index of suspicion for the possibility of ASM is necessary to ensure drug
      discontinuation and recovery. This is particularly true since the entity is not
      widely recognized and its symptoms are often erroneously interpreted as due to
      the patient's underlying disease.

PMID- 29462473
TI  - Stochastic Pharmacokinetic-Pharmacodynamic Modeling for Assessing the Systemic
      Health Risk of Perfluorooctanoate (PFOA).
AB  - A phase 1 dose-escalation trial assessed the chemotherapeutic potential of
      ammonium perfluorooctanoate (APFO). Forty-nine primarily solid-tumor cancer
      patients who failed standard therapy received weekly APFO doses (50-1200 mg) for
      6 weeks. Clinical chemistries and plasma PFOA (anionic APFO) were measured
      predose and weekly thereafter. Several clinical measures including total
      cholesterol, high-density lipoproteins (HDLs), thyroid stimulating hormone (TSH),
      and free thyroxine (fT4), relative to PFOA concentrations were examined by:
      Standard statistical analyses using generalized estimating equations (GEE) and a
      probabilistic analysis using probability distribution functions (pdf) at various
      PFOA concentrations; and a 2-compartment pharmacokinetic/pharmacodynamic (PK/PD)
      model to directly estimate mean changes. Based on the GEE, the average rates of
      change in total cholesterol and fT4 associated with increasing PFOA were
      approximately -1.2*10-3 mmol/l/MUM and 2.8*10-3 pmol/l/MUM, respectively. The
      PK/PD model predicted more closely the trends observed in the data as well as the
      pdfs of biomarkers. A decline in total cholesterol was observed, with a clear
      transition in shape and range of the pdfs, manifested by the maximum value of the
      Kullback-Leibler (KL) divergence, that occurred at plasma PFOA between 420 and
      565 MUM (175 000-230 000 ng/ml). High-density lipoprotein was unchanged. An
      increase in fT4 was observed at a higher PFOA transition point, albeit TSH was
      unchanged. Our findings are consistent with some animal models and may motivate
      re-examination of the epidemiologic studies to PFOA at levels several orders of
      magnitude lower than this study. These observational studies have reported
      contrary associations, but currently understood biology does not support the
      existence of such conflicting effects.

PMID- 29462476
TI  - Malassezia pachydermatis up-regulates AhR related CYP1A1 gene and epidermal
      barrier markers in human keratinocytes.
AB  - Cytochrome P450 CYP1A1 and CYP1B1 enzymes are regulated by the aryl hydrocarbon
      receptor (AhR), a transcription factor activated by a variety of ligands among
      which Malassezia metabolites. In this study, we analyzed the modulation of
      CYP1A1, CYP1B1, and AhR in human keratinocytes infected with different strains of
      Malassezia pachydermatis, as well as the upregulation of some genes involved in
      the epidermal homeostasis. We demonstrated that all the strains induced AhR
      activation and its nuclear translocation in HaCaT cells infected for 24 h,
      compared to untreated cells. The expression of CYP1A1 and CYP1B1, prototypical
      markers of the AhR signaling pathway, were upregulated with the level of CYP1A1
      mRNA approximately 100-fold greater than that for CYP1B1. Filaggrin, involucrin,
      and TGaseI, proteins involved in epidermal differentiation, were all modulated by
      Malassezia pachydermatis strains, with the strongest induction observed for
      filaggrin. By contrast, quinone oxidoreductase 1 (NQO1), which is part of the
      antioxidant defense system involved in detoxification, was not modulated in our
      experimental model. In conclusions, our findings suggest that Malassezia
      pachydermatis infection of human keratinocytes induces activation of the AhR, and
      increases the expression of its responsive genes and markers of epidermal
      differentiation, paving the way for occurrence/exacerbation of pathological skin
      conditions.

PMID- 29462475
TI  - Choosing to regulate: does choice enhance craving regulation?
AB  - Goal-directed behavior and lifelong well-being often depend on the ability to
      control appetitive motivations, such as cravings. Cognitive reappraisal is an
      effective way to modulate emotional states, including cravings, but is often
      studied under explicit instruction to regulate. Despite the strong prediction
      from Self-Determination Theory that choice should enhance task engagement and
      regulation success, little is known empirically about whether and how regulation
      is different when participants choose (vs are told) to exert control. To
      investigate how choice affects neural activity and regulation success,
      participants reappraised their responses to images of personally-craved foods
      while undergoing functional neuroimaging. Participants were either instructed to
      view or reappraise ('no-choice') or chose freely to view or reappraise ('yes
      choice'). Choice increased activity in the frontoparietal control network. We
      expected this activity would be associated with increased task engagement,
      resulting in better regulation success. However, contrary to this prediction,
      choice slightly reduced regulation success. Follow-up multivariate functional
      neuroimaging analyses indicated that choice likely disrupted allocation of
      limited cognitive resources during reappraisal. While unexpected, these results
      highlight the importance of studying upstream processes such as regulation
      choice, as they may affect the ability to regulate cravings and other emotional
      states.

PMID- 29462478
TI  - An Engaged Electronic Medical Record for Social Good.

PMID- 29462477
TI  - Meat quality traits in the Greater rhea (Rhea americana) as influenced by muscle,
      sex and age.
AB  - Meat from the Greater rhea (Rhea americana) could compete with traditional red
      meats, diversifying the market of protein products of animal origin. The meat
      from 32 rheas was used to study quality aspects and this included ultimate pH
      (pHu), color, water-holding capacity (WHC%), cooking loss (CL%) and tenderness.
      The muscles sampled were the Gastrocnemius pars externa, Iliofibularis and
      Obturatorius medialis from both sexes at multiple ages (10, 12, 14, 16 months).
      Age at slaughter affected WHC%, CL%, and color in raw meat and tenderness in
      cooked meat. Muscles under study showed differences in terms of pHu, raw meat
      color, and tenderness of cooked meat. Sex did not have a significant effect on
      any of the variables studied. According to our results, rhea meat from younger
      animals, between 10 to 14 months old, was tender and moderately juicy and the
      visual color was appreciated by the consumers.

PMID- 29462479
TI  - EVALUATION OF PATIENT EXPOSURE IN FAST kVp SWITCHING DUAL ENERGY COMPUTED
      TOMOGRAPHY: PHANTOM STUDY.
AB  - The aim of this study was to evaluate the suitability of size specific dose
      estimates (SSDE) to estimate patient dose in Fast kVp switching dual energy CT.
      An anthropomorphic phantom (RAN-110) was repeatedly scanned (chest, abdomen and
      the pelvis) using a 64 detector row MDCT (Discovery CT750 HD, GE Healthcare,
      Milwaukee, WI, USA) with various CT parameters, including Fast kVp switching.
      Dosimetry was performed using thermo-luminescent dosimeters, positioned both
      superficially and within the phantom. SSDE was calculated for all slices of the
      anthropomorphic phantom using both the localiser and axial images. In Fast kVp
      switching, SSDE underestimated the measured absorbed dose for the chest/abdomen
      region ~35% at the maximum, but were in closer agreement for the pelvic region
      about within 10%. In single energy techniques, SSDE could not be applied in the
      estimation of organ doses, but in Fast kVp switching dual energy techniques, SSDE
      could be applied for anatomical regions with larger thicknesses.

PMID- 29462480
TI  - Testicular histomorphometrics including Sertoli cell quantitation for evaluating
      hatchability and fertility issues in commercial breeder-broiler roosters.
AB  - Testicular histomorphometric methods were developed for the investigation of
      fertility and hatchability problems in commercial broiler-breeder roosters.
      Sertoli cell (SC) evaluations were emphasized in view of their role in
      influencing embryonic testicular organogenesis and spermatogenesis in adults. H&E
      stained sections prepared from formalized tissues were examined. SC evaluations
      were mostly made from computer generated images using image analysis software,
      but were also compared to direct counting with ocular grid reticle. Other
      measurements were germinal epithelial and total seminiferous tubule widths,
      quantification of individual spermatozoa and sperm clusters, and determinations
      of stromal area. Age-associated changes in SC occurred between 15 to 54 wk of
      age. A significant reduction in SC concentration occurred at 29 wk of age (P <
      0.001) that corresponded with the histologic initiation of spermatogenesis.
      Expanded morphometric evaluations were performed on 59-week-old roosters
      comparing a flock having good body condition and footpad scores with normal
      testicular and body weights (optimal profile or OP group) to a second flock
      demonstrating relatively poor expression of these parameters and decreased
      fertility (sub-optimal profile or SOP group). Significant reductions (P < 0.05)
      in SC concentration, spermatozoa, and tubular widths, but an increased percentage
      of stroma area occurred in SOP compared to OP flocks. SC results also correlated
      well with testes weight. A unique finding was a significant relationship between
      decreasing SC concentration and increasing severity scores for footpad lesions.
      Differences in all histomorphometric parameters occurred between flocks
      demonstrating good hatchability compared to flocks exhibiting either low or
      decreasing hatchability. Significant reductions in SC and other morphometric
      parameters were observed for the poor relative to good hatchability group. A
      strong positive association was observed for SC results using computer generated
      images and direct reticle ocular counting (R = 0.80). Replicate counts on control
      sections demonstrated generally good reproducibility of methods between
      experiments. The findings are supportive of the value of testicular
      histomorphometrics for evaluations of hatchability issues in commercial roosters.

PMID- 29462481
TI  - Greater involvement of action simulation mechanisms in emotional versus cognitive
      empathy.
AB  - Empathy is crucial for successful interpersonal interactions, and it is impaired
      in many psychiatric and neurological disorders. Action-perception matching, or
      action simulation mechanisms, have been suggested to facilitate empathy by
      supporting the simulation of perceived experience in others. However, this
      remains unclear, and the involvement of the action simulation circuit in
      cognitive empathy (the ability to adopt another's perspective) versus emotional
      empathy (the capacity to share and react affectively to another's emotional
      experience) has not been quantitatively compared. Presently, healthy adults
      completed a classic cognitive empathy task (false belief), an emotional empathy
      task, and an action simulation button-pressing task during fMRI. Conjunction
      analyses revealed common recruitment of the inferior frontal gyrus (IFG), thought
      to be critical for action-perception matching, during both action simulation and
      emotional, but not cognitive, empathy. Furthermore, activation was significantly
      greater in action simulation regions in the left IFG during emotional versus
      cognitive empathy, and activity in this region was positively correlated with
      mean feeling ratings during the emotional empathy task. These findings provide
      evidence for greater involvement of action simulation mechanisms in emotional
      than cognitive empathy. Thus, the action simulation circuit may be an important
      target for delineating the pathophysiology of disorders featuring emotional
      empathy impairments.

PMID- 29462483
TI  - ESTIMATION OF DIAGNOSTIC REFERENCE LEVELS FOR CT CORONAROGRAPHY IN SLOVAKIA.
AB  - The coronary CT angiography (CCTA) is a frequent diagnostic method connected with
      large variability of effective dose. Therefore, it is the type of examination
      where optimization is very important and the use of a national diagnostic
      reference level (DRL) recommended. In Slovakia the DRL for interventional
      radiology examinations until now fails. The objective of our study was to propose
      the national DRL for CCTA examinations in Slovak Republic, on the basis of a
      cross-sectional multicenter study, performed in four departments of radiology.
      The study was realized in 2014-16 in a sample of 1725 patients undergoing CCTA
      examination. The proposed DRL expressed by CTDIVOL is 45 mGy and of DLP is 510
      mGy cm.

PMID- 29462482
TI  - A randomized Phase III trial of adjuvant S-1 therapy vs. observation alone in
      resected biliary tract cancer: Japan Clinical Oncology Group Study (JCOG1202,
      ASCOT).
AB  - No standard adjuvant treatment has been established for patients with curatively
      resected biliary tract cancer. S-1 has been reported to show promising efficacy
      with mild toxicity profiles in patients with advanced biliary tract cancer, and
      adjuvant S-1 therapy has been demonstrated to provide survival benefit in
      patients with resected gastric cancer and pancreatic cancer. The aim of this open
      label, multicenter, randomized Phase III trial is to confirm that adjuvant
      chemotherapy with S-1 would prolong overall survival in patients with resected
      biliary tract cancer. This study was activated in September 2013. A total of 350
      patients planned to be enrolled from 36 Japanese institutions over a period of 4
      years. At July 2017, the protocol was revised to increase power from 70% to 80%.
      Therefore, the planned total sample size is 440. The primary endpoint is overall
      survival. This trial is registered with the UMIN Clinical Trials Registry as
      UMIN000011688.

PMID- 29462484
TI  - A Review of Industry Funding in Randomized Controlled Trials Published in the
      Neurosurgical Literature-The Elephant in the Room.
AB  - OBJECTIVE: To analyze the role of industry sponsorship of randomized controlled
      trials (RCTs) published exclusively in 3 major North American neurosurgical
      journals. METHODS: Our primary objective was to determine whether an association
      exists between study conclusion(s) in favor of industry sponsored drugs,
      devices/implants, or surgical techniques and industry sponsorship. The secondary
      objective was to describe the quality/quantity of these neurosurgical RCTs.
      RESULTS: A total of 110 RCTs were analyzed, the majority were published in the
      Journal of Neurosurgery (85%) and were international in origin (55%). The most
      common subspecialty was spine (n = 29) and drug study was the most common type (n
      = 49). Overall quality was good with median Jadad and Detsky scores of 4 (range,
      1-5) and 18 (range, 8-21), respectively. There was a statistically significant
      difference in RCTs with industry funding (31/40, 78%) versus those without (9/70,
      13%) that published a favorable conclusion of the new drug, device/implant, or
      surgical technique (odds ratio [OR], 23.35; P < .0001). Multiple binomial
      logistic regression analysis identified "number of authors" as mildly protective
      (OR, 0.79; 95% confidence interval, 0.69-0.91; P = .001) and "industry funding"
      strongly predictive (OR, 12.34; 95% confidence interval, 2.97-51.29; P = .001) of
      a positive trial. CONCLUSION: Industry funding was associated with a much greater
      chance of positive findings in RCTs published in neurosurgical journals. Further
      efforts are needed to define the relationship between the authors and financial
      sponsors of neurosurgical research and explore the reasons for this finding.

PMID- 29462485
TI  - In Reply: Low-Pressure Hydrocephalus in Children: A Case Series and Review of the
      Literature.

PMID- 29462486
TI  - "Cracking" into the debate about laying hen housing.
AB  - Livestock production systems have faced social pressures related to animal
      welfare; the laying hen industry also has faced changes in governing
      regulations/policies. This study employs experimental data to evaluate 3
      confinement-housing systems: standard cages with no perches, cages with standard
      perches, and cages with cooled perches. Based on the cost-benefit analysis
      conducted of revenue less feed costs, operators are expected to have revenue,
      after covering feed costs, which could contribute to installation and maintenance
      of standard and/or cooled perches. Thus, egg producers may be able to use caged
      housing that incorporates perches profitably, depending on the final costs of
      such a system.

PMID- 29462487
TI  - Structural change of ovalbumin-related protein X by alkali treatment.
AB  - Chicken egg white protein ovalbumin (OVA) undergoes a conversion to a more
      thermostable form by alkali treatment, which is assumed to be involved in the
      physiological functions of OVA. Ovalbumin-related protein X (OVAX), a chicken egg
      white protein, has 77% sequence similarity to OVA and binds to heparin. In this
      study, structure characteristics and heparin-binding affinity of alkali-treated
      OVAX were investigated. Cation-exchange chromatography using SP Sepharose resin
      showed that alkali treatment (pH 10, 55 degrees C) of OVAX induces the occurrence
      of a distinct OVAX form with a less positive-charge (acidic OVAX). Circular
      dichroism and tryptophan-fluorescence analyses showed that the newly-formed
      acidic OVAX form has an 8% lower alpha-helical content than its native
      counterpart, while there is no significant difference in steric environments
      around tryptophan residues between the 2 forms. The OVAX structure built by
      homology-modeling showed that OVAX possess a basic cluster domain with alpha
      helix equivalent to 7% of total secondary structures, which does not contain any
      tryptophan residues. These results suggest that, during alkali treatment, OVAX
      undergoes mainly a conformational change of the alpha-helical basic cluster
      domain and thereby forms acidic OVAX. Acidic OVAX induced by alkali treatment
      exhibited weaker interactions with Heparin Sepharose resin than native OVAX did.
      Our results suggest that OVAX basic cluster domain is likely a specific binding
      site of heparin. Consequently, it is suggested that alkali treatment causes the
      collapse of the OVAX heparin binding site, which might participate in regulating
      the functions of heparin.

PMID- 29462488
TI  - Computational model for behavior shaping as an adaptive health intervention
      strategy.
AB  - Adaptive behavioral interventions that automatically adjust in real-time to
      participants' changing behavior, environmental contexts, and individual history
      are becoming more feasible as the use of real-time sensing technology expands.
      This development is expected to improve shortcomings associated with traditional
      behavioral interventions, such as the reliance on imprecise intervention
      procedures and limited/short-lived effects. JITAI adaptation strategies often
      lack a theoretical foundation. Increasing the theoretical fidelity of a trial has
      been shown to increase effectiveness. This research explores the use of shaping,
      a well-known process from behavioral theory for engendering or maintaining a
      target behavior, as a JITAI adaptation strategy. A computational model of
      behavior dynamics and operant conditioning was modified to incorporate the
      construct of behavior shaping by adding the ability to vary, over time, the range
      of behaviors that were reinforced when emitted. Digital experiments were
      performed with this updated model for a range of parameters in order to identify
      the behavior shaping features that optimally generated target behavior. Narrowing
      the range of reinforced behaviors continuously in time led to better outcomes
      compared with a discrete narrowing of the reinforcement window. Rapid narrowing
      followed by more moderate decreases in window size was more effective in
      generating target behavior than the inverse scenario. The computational shaping
      model represents an effective tool for investigating JITAI adaptation strategies.
      Model parameters must now be translated from the digital domain to real-world
      experiments so that model findings can be validated.

PMID- 29462490
TI  - Open surgical repair of post-dissection thoraco-abdominal aortic aneurysms: early
      and late outcomes of a single-centre study involving over 200 patients.
AB  - OBJECTIVES: Chronic, post-dissection thoraco-abdominal aortic aneurysms (TAAAs)
      are increasingly being treated by (hybrid) endovascular means. Although it is
      less invasive, thoracic endovascular aortic repair is technically complex with
      the risk of incomplete aneurysm exclusion, necessitating frequent reinterventions
      with potentially reduced long-term outcomes. The aim of this study was to
      evaluate contemporary early and late outcomes after open surgical repair of post
      dissection TAAA. METHODS: At our centre, 633 patients underwent open repair for
      TAAA over a 20-year period (1994-2015), including 217 (34%) patients for post
      dissection TAAA, who were included in this analysis. Circulatory support was
      obtained by either left heart bypass (173 patients, 79.7%), deep hypothermic
      circulatory arrest (41 patients, 18.9%) or simple aortic cross-clamping in 3
      patients. We analysed all relevant perioperative and intraoperative variables
      with respect to adverse outcomes. Additionally, long-term survival and the need
      for aortic reinterventions were studied. RESULTS: The mean age was 60.2 +/- 11.9
      years (men 68.2%). We identified 66 Type I (30.4%), 113 Type II (52.1%), 25 Type
      III (11.5%), 10 Type IV (4.6%) and 3 Type V (1.4%) TAAAs. Early mortality and
      spinal cord deficit were 5.9% and 5.5%, respectively. Follow-up was 100% complete
      (mean 6.0 +/- 5.8 years), with long-term survival of 71.4% at 10 years, and
      freedom from death and reoperation was 68.2% at 10 years. CONCLUSIONS: Although
      it is more invasive than current endovascular approaches for post-dissection
      TAAA, open surgical repair can be performed safely with acceptable rates of
      morbidity and mortality when it is done in a specialized aortic centre. Long-term
      survival and freedom from aortic reintervention are excellent and should also be
      taken into account when evaluating less invasive alternatives.

PMID- 29462489
TI  - DNA methylation dynamics of genomic imprinting in mouse development.
AB  - DNA methylation is an essential epigenetic mark crucial for normal mammalian
      development. This modification controls the expression of a unique class of
      genes, designated as imprinted, which are expressed monoallelically and in a
      parent-of-origin-specific manner. Proper parental allele-specific DNA methylation
      at imprinting control regions (ICRs) is necessary for appropriate imprinting.
      Processes that deregulate DNA methylation of imprinted loci cause disease in
      humans. DNA methylation patterns dramatically change during mammalian
      development: first, the majority of the genome, with the exception of ICRs, is
      demethylated after fertilization, and subsequently undergoes genome-wide de novo
      DNA methylation. Secondly, after primordial germ cells are specified in the
      embryo, another wave of demethylation occurs, with ICR demethylation occurring
      late in the process. Lastly, ICRs reacquire DNA methylation imprints in
      developing germ cells. We describe the past discoveries and current literature
      defining these crucial dynamics in relation to imprinted genes and the rest of
      the genome.

PMID- 29462491
TI  - The beta-adrenergic agonist salbutamol modulates neuromuscular junction formation
      in zebrafish models of human myasthenic syndromes.
AB  - Inherited defects of the neuromuscular junction (NMJ) comprise an increasingly
      diverse range of disorders, termed congenital myasthenic syndromes (CMS).
      Therapies acting on the sympathetic nervous system, including the selective beta2
      adrenergic agonist salbutamol and the alpha and beta adrenergic agonist
      ephedrine, have become standard treatment for several types of CMS. However, the
      mechanism of the therapeutic effect of sympathomimetics in these disorders is not
      understood. Here, we examined the effect of salbutamol on NMJ development using
      zebrafish with deficiency of the key postsynaptic proteins Dok-7 and MuSK.
      Treatment with salbutamol reduced motility defects in zebrafish embryos and
      larvae. In addition, salbutamol lead to morphological improvement of postsynaptic
      acetycholine receptor (AChR) clustering and size of synaptic contacts in Dok-7
      deficient zebrafish. In MuSK-deficient zebrafish, salbutamol treatment reduced
      motor axon pathfinding defects and partially restored the formation of aneural
      prepatterned AChRs. In addition, the effects of salbutamol treatment were
      prevented by pre-treatment with a selective beta2 antagonist. Treatment with the
      cyclic adenosine monophosphate (cAMP) activator forskolin, replicated the effects
      of salbutamol treatment. These results suggest that sympathomimetics exert a
      direct effect on neuromuscular synaptogenesis and do so via beta2 adrenoceptors
      and via a cAMP-dependent pathway.

PMID- 29462492
TI  - Chronic Helminth Infection Perturbs the Gut-Brain Axis, Promotes Neuropathology,
      and Alters Behavior.
AB  - Helminth infections in children are associated with impaired cognitive
      development; however, the biological mechanisms for this remain unclear. Using a
      murine model of gastrointestinal helminth infection, we demonstrate that early
      life exposure to helminths promotes local and systemic inflammatory responses and
      transient changes in the gastrointestinal microbiome. Behavioral and cognitive
      analyses performed 9-months postinfection revealed deficits in spatial
      recognition memory and an anxiety-like behavioral phenotype in worm-infected
      mice, which was associated with neuropathology and increased microglial
      activation within the brain. This study demonstrates a previously unrecognized
      mechanism through which helminth infections may influence cognitive function, via
      perturbations in the gut-immune-brain axis.

PMID- 29462493
TI  - Short delay in initiation of radiotherapy for patients with glioblastoma-effect
      of concurrent chemotherapy: a secondary analysis from the NRG Oncology/Radiation
      Therapy Oncology Group database.
AB  - Background: We previously reported the unexpected finding of significantly
      improved survival for newly diagnosed glioblastoma in patients when radiation
      therapy (RT) was initiated later (>4 wk post-op) compared with earlier (<=2 wk
      post-op). In that analysis, data were analyzed from 2855 patients from 16 NRG
      Oncology/Radiotherapy Oncology Group (RTOG) trials conducted prior to the era of
      concurrent temozolomide (TMZ) with RT. We now report on 1395 newly diagnosed
      glioblastomas from 2 studies, treated with RT and concurrent TMZ followed by
      adjuvant TMZ. Our hypothesis was that concurrent TMZ has a
      synergistic/radiosensitizing mechanism, making RT timing less significant.
      Methods: Data from patients treated with TMZ-based chemoradiation from NRG
      Oncology/RTOG 0525 and 0825 were analyzed. An analysis comparable to our prior
      study was performed to determine whether there was still an impact on survival by
      delaying RT. Overall survival (OS) was investigated using the Kaplan-Meier method
      and Cox proportional hazards model. Early progression (during time of diagnosis
      to 30 days after RT completion) was analyzed using the chi-square test. Results:
      Given the small number of patients who started RT early following surgery,
      comparisons were made between >4 and <=4 weeks delay of radiation from time of
      operation. There was no statistically significant difference in OS (hazard ratio
      = 0.93; P = 0.29; 95% CI: 0.80-1.07) after adjusting for known prognostic factors
      (recursive partitioning analysis and O6-methylguanine-DNA methyltransferase
      methylation status). Similarly, the rate of early progression did not differ
      significantly (P = 0.63). Conclusions: We did not observe a significant
      prognostic influence of delaying radiation when given concurrently with TMZ for
      newly diagnosed glioblastoma. The effects of early (1-3 wk post-op) or late (>5
      wk) initiation of radiation tested in our prior study could not be replicated.

PMID- 29462494
TI  - Why did severe feather pecking and cannibalism outbreaks occur? An unintended
      case study while investigating the effects of forage and stress on pullets during
      rearing.
AB  - This 2 * 2 factorial experiment aimed to investigate the effects of stimulating
      foraging behavior from wk 6 and imposed stress at wk 16 on the development of
      severe feather pecking (SFP) in chickens reared for free-range egg production.
      Non-beak-trimmed ISA Brown chicks were purchased at one day old and floor-reared
      on wood shavings. From wk 6, straw was provided daily in dispensers (Forage vs.
      No forage) to stimulate foraging. At wk 15, there were 16 pens of 50 pullets.
      "Stressors" were applied to half the pens in wk 16 via combined transport,
      relocation, and mixing (TRM) of pullets, simulating activities around transfer
      from the rearing to egg-laying farm (TRM vs. Not TRM). Range access was permitted
      from wk 21. Behavior, plumage damage (PD), growth, egg production, feed use,
      injuries, and mortalities were recorded, along with litter moisture and pH. In wk
      26, an SFP outbreak commenced. By wk 34, PD was worse in south- than north-aspect
      pens (P < 0.001). Further, PD was more affected by side of the shed than the
      experimental treatments. In wk 30, an outbreak of injurious pecking (IP)
      commenced in the 4 TRM-treatment pens on the south side, with IP deaths almost 3
      times more common in the Forage+TRM than No forage+TRM treatment. We suggest
      factors associated with a 13-day rainfall event that occurred in late winter
      predisposed the flock to SFP. While multiple factors such as winter cold, muddy
      ranges, damp floor litter with elevated pH, among others coincided, hens were
      clearly more impacted in south- than north-aspect pens. Once initiated, SFP
      possibly spread via social learning, and by wk 40, ~98% of hens had PD.
      Interestingly, the IP outbreak was related to a combination of factors
      (stressors?), such as being housed in colder, damper south-aspect pens (note:
      southern hemisphere), having added Forage, and TRM. These unexpected
      relationships could help direct future research to identify the specific factors
      involved in the causation of SFP and IP/cannibalism outbreaks.

PMID- 29462496
TI  - Experiences and unmet needs of lesbian, gay, and bisexual people with cancer
      care: A systematic review and meta-synthesis.
AB  - OBJECTIVES: To explore the cancer care experiences and unmet needs of people who
      identify as a sexual or gender minority. METHODS: A qualitative systematic review
      and meta-synthesis was undertaken based on a registered protocol. Following
      literature searching and study selection, study quality was examined by using the
      Critical Appraisal Skill Programme Checklist. Qualitative data were extracted
      verbatim from included studies and synthesized by using thematic analysis.
      RESULTS: Fifteen studies that included lesbian, gay, and bisexual (LGB) people
      living with or beyond cancer were included in the review. Studies including
      gender minorities were not identified. Most of the study participants were sexual
      minority women with breast cancer or sexual minority men with prostate cancer.
      Meta-synthesis of 106 individual findings generated 6 overarching themes
      pertaining to sexual orientation disclosure, experiences and fear of homophobia,
      positive and negative health-care professional behaviors, heterocentric systems
      and care, inadequacy of available support groups, and unmet needs for patient
      centered care and LGB-specific information. Lesbian, gay, and bisexual people
      often reported feelings of anxiety, invisibility, isolation, and frustration
      throughout the cancer care continuum. CONCLUSIONS: Analysis of the experiences of
      LGB people with cancer care shows that LGB people face numerous challenges due to
      their sexual orientation and receive care that does not adequately address their
      needs. Training and education of health-care professionals are strongly
      recommended to address some of these challenges and practice gaps. Culturally
      appropriate care includes avoiding heterosexual assumptions, use of inclusive
      language, the provision of tailored information, and involving partners in care.

PMID- 29462495
TI  - Comparison of Methods for Molecular Species Delimitation Across a Range of
      Speciation Scenarios.
AB  - Species are fundamental units in biological research and can be defined on the
      basis of various operational criteria. There has been growing use of molecular
      approaches for species delimitation. Among the most widely used methods, the
      generalized mixed Yule-coalescent (GMYC) and Poisson tree processes (PTP) were
      designed for the analysis of single-locus data but are often applied to
      concatenations of multilocus data. In contrast, the Bayesian multispecies
      coalescent approach in the software Bayesian Phylogenetics and Phylogeography
      (BPP) explicitly models the evolution of multilocus data. In this study, we
      compare the performance of GMYC, PTP, and BPP using synthetic data generated by
      simulation under various speciation scenarios. We show that in the absence of
      gene flow, the main factor influencing the performance of these methods is the
      ratio of population size to divergence time, while number of loci and sample size
      per species have smaller effects. Given appropriate priors and correct guide
      trees, BPP shows lower rates of species overestimation and underestimation, and
      is generally robust to various potential confounding factors except high levels
      of gene flow. The single-threshold GMYC and the best strategy that we identified
      in PTP generally perform well for scenarios involving more than a single putative
      species when gene flow is absent, but PTP outperforms GMYC when fewer species are
      involved. Both methods are more sensitive than BPP to the effects of gene flow
      and potential confounding factors. Case studies of bears and bees further
      validate some of the findings from our simulation study, and reveal the
      importance of using an informed starting point for molecular species
      delimitation. Our results highlight the key factors affecting the performance of
      molecular species delimitation, with potential benefits for using these methods
      within an integrative taxonomic framework.

PMID- 29462497
TI  - Accuracy of self-reported hypertension in Brazilian adolescents: Analysis of the
      Study of Cardiovascular Risk in Adolescents.
AB  - Given the high prevalence of hypertension in adolescents, it is important to
      investigate alternatives for estimating the magnitude of the disease. Our
      objective was to investigate the accuracy of self-reported hypertension. The
      study assessed participants of the Study of Cardiovascular Risk in Adolescents
      (ERICA). The following were calculated: sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV). The associations
      between inaccurate self-reporting and socioeconomic factors were investigated.
      The accuracy of self-reported hypertension had a sensitivity of 7.5% (95% CI, 6.9
      8.2), a specificity of 96.6% (95% CI, 96.5-96.7), a PPV of 18.9% (95% CI, 17.4
      20.5), and a NPV of 90.8% (95% CI, 90.6-91.0). The prevalence of inaccurate self
      reported hypertension was smaller among girls (PR 0.68; 95% CI, 0.55-0.83) and
      younger boys (PR 0.68; 95% CI, 0.54-0.86) who were attending private schools. The
      use of self-reported hypertension was not a good strategy for investigating the
      hypertension in adolescents.

PMID- 29462498
TI  - Odorant Receptor 7D4 Activation Dynamics.
AB  - Deciphering how an odorant activates an odorant receptor (OR) and how changes in
      specific OR residues affect its responsiveness are central to understanding our
      sense of smell. A joint approach combining site-directed mutagenesis and
      functional assays with computational modeling has been used to explore the
      signaling mechanics of OR7D4. In this OR, a genetic polymorphism affects our
      perception of androstenone. Molecular simulations totaling 0.12 ms predicted
      that, similarly to observations for other G-protein-coupled receptors with known
      experimental structures, an activation pathway connects the ligand and the G
      protein binding site. The 3D model activation mechanism correlates with in vitro
      data and notably predicts that the OR7D4 WM variant is not activated. Upon
      activation, an OR-specific sequence motif is the convergence point of the
      mechanism. Our study suggests that robust homology modeling can serve as a
      powerful tool to capture OR dynamics related to smell perception.

PMID- 29462499
TI  - Following patient pathways to psycho-oncological treatment: Identification of
      treatment needs by clinical staff and electronic screening.
AB  - OBJECTIVE: In this retrospective investigation of patient pathways to psycho
      oncological treatment (POT), we compared the number of POT referrals before and
      after implementation of electronic screening for POT needs and investigated
      psychosocial predictors for POT wish at a nuclear medicine department. METHODS:
      We extracted medical chart information about number of referrals and extent of
      follow-up contacts. During standard referral (November 2014 to October 2015), POT
      needs were identified by clinical staff only. In the screening-assisted referral
      period (November 2015 to October 2016), identification was supported by
      electronic screening for POT needs. Psychosocial predictors for POT wish were
      examined using logistic regression. RESULTS: We analysed data from 487 patients
      during standard referral (mean age 56.4 years; 60.2% female, 88.7% thyroid
      carcinoma or neuroendocrine tumours) of which 28 patients (5.7%) were referred
      for POT. Of 502 patients in the screening-assisted referral period (mean age 57.0
      years; 55.8% female, 86.6% thyroid carcinoma or neuroendocrine tumours), 69
      (13.7%) were referred for POT. Of these, 36 were identified by psycho-oncological
      (PO) screening and 33 by clinical staff. After PO-screening implementation,
      referrals increased by a factor of 2.4. The strongest predictor of POT wish was
      depressive mood (P < .001). During both referral periods, about 15% of patients
      visited the PO outpatient unit additionally to inpatient PO consultations.
      CONCLUSIONS: Our results provide evidence from a real-life setting that PO
      screening can foster POT referrals, reduce barriers to express the POT wish, and
      hence help to meet psychosocial needs of this specific patient group. Differences
      between patients' needs, wish, and POT uptake should be further investigated.

PMID- 29462500
TI  - Antifibrinolytic drugs for treating primary postpartum haemorrhage.
AB  - BACKGROUND: Postpartum haemorrhage (PPH) - heaving bleeding within the first 24
      hours after giving birth - is one of the main causes of death of women after
      childbirth. Antifibrinolytics, primarily tranexamic acid (TXA), have been shown
      to reduce bleeding in surgery and safely reduces mortality in trauma patients
      with bleeding without increasing the risk of adverse events.An earlier Cochrane
      review on treatments for primary PPH covered all the various available treatments
      - that review has now been split by types of treatment. This new review
      concentrates only on the use of antifibrinolytic drugs for treating primary PPH.
      OBJECTIVES: To determine the effectiveness and safety of antifibrinolytic drugs
      for treating primary PPH. SEARCH METHODS: We searched Cochrane Pregnancy and
      Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical
      Trials Registry Platform (ICTRP) (28 May 2017) and reference lists of retrieved
      studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), including
      cluster-randomised trials of antifibrinolytic drugs (aprotinin, TXA, epsilon
      aminocaproic acid (EACA) and aminomethylbenzoic acid, administered by whatever
      route) for primary PPH in women.Participants in the trials were women after birth
      following a pregnancy of at least 24 weeks' gestation with a diagnosis of PPH,
      regardless of mode of birth (vaginal or caesarean section) or other aspects of
      third stage management.We have not included quasi-randomised trials, or cross
      over studies. Studies reported as abstracts have not been included if there was
      insufficient information to allow assessment of risk of bias.In this review we
      only identified studies looking at TXA. DATA COLLECTION AND ANALYSIS: Two review
      authors independently extracted data from each study using an agreed form. We
      entered data into Review Manager software and checked for accuracy.For key review
      outcomes, we rated the quality of the evidence as 'high', 'moderate', 'low' or
      'very low' according to the GRADE approach. MAIN RESULTS: Three trials (20,412
      women) met our inclusion criteria. Two trials (20,212 women) compared intravenous
      (IV) TXA with placebo or standard care and were conducted in acute hospital
      settings (labour ward, emergency department) (in high-, middle- and low-income
      countries).One other trial (involving 200 women) was conducted in Iran and
      compared IV TXA with rectal misoprostol, but did not report on any of this
      review's primary or GRADE outcomes. There were no trials that assessed EACA,
      aprotinin or aminomethylbenzoic acid.Standard care plus IV TXA for the treatment
      of primary PPH compared with placebo or standard care aloneTwo trials (20,212
      women) assessed the effect of TXA for the treatment of primary PPH compared with
      placebo or standard care alone. The larger of these (The WOMAN trial) contributed
      over 99% of the data and was assessed as being at low risk of bias. The quality
      of the evidence varied for different outcomes, Overall, evidence was mainly
      graded as moderate to high quality.The data show that IV TXA reduces the risk of
      maternal death due to bleeding (risk ratio (RR) 0.81, 95% confidence interval
      (CI) 0.65 to 1.00; two trials, 20,172 women; quality of evidence: moderate). The
      quality of evidence was rated as moderate due to imprecision of effect estimate.
      The effect was more evident in women given treatment between one and three hours
      after giving birth with no apparent reduction when given after three hours (< one
      hour = RR 0.80, 95% CI 0.55 to 1.16; one to three hours = RR 0.60, 95% CI 0.41 to
      0.88; > three hours = RR 1.07, 95% 0.76 to 1.51; test for subgroup differences:
      Chi2 = 4.90, df = 2 (P = 0.09), I2 = 59.2%). There was no heterogeneity in the
      effect by mode of birth (test for subgroup differences: Chi2 = 0.01, df = 1 (P =
      0.91), I2 = 0%). There were fewer deaths from all causes in women receiving TXA,
      although the 95% CI for the effect estimate crosses the line of no effect (RR
      0.88, 95% CI 0.74 to 1.05; two trials, 20,172 women, quality of evidence:
      moderate). Results from one trial with 151 women suggest that blood loss of >=
      500 mL after randomisation may be reduced (RR 0.50, 95% CI 0.27 to 0.93; one
      trial, 151 women; quality of evidence: low). TXA did not reduce the risk of
      serious maternal morbidity (RR 0.99, 95% CI 0.83 to 1.19; one trial, 20,015
      women; quality of evidence: high), hysterectomy to control bleeding (RR 0.95, 95%
      CI 0.81 to 1.12; one trial, 20,017 women; quality of evidence: high) receipt of
      blood transfusion (any) (RR 1.00, 95% CI 0.97 to 1.03; two trials, 20,167 women;
      quality of evidence: moderate) or maternal vascular occlusive events (any),
      although results were imprecise for this latter outcome (RR 0.88, 95% CI 0.54 to
      1.43; one trial, 20,018 women; quality of evidence: moderate). There was an
      increase in the use of brace sutures in the TXA group (RR 1.19, 95% CI 1.01,
      1.41) and a reduction in the need for laparotomy for bleeding (RR 0.64, 95% CI
      0.49, 0.85). AUTHORS' CONCLUSIONS: TXA when administered intravenously reduces
      mortality due to bleeding in women with primary PPH, irrespective of mode of
      birth, and without increasing the risk of thromboembolic events. Taken together
      with the reliable evidence of the effect of TXA in trauma patients, the evidence
      suggests that TXA is effective if given as early as possible.Facilities for IV
      administration may not be available in non-hospital settings therefore,
      alternative routes to IV administration need to be investigated.

PMID- 29462501
TI  - Preparation and preliminary in vivo evaluation of 166 Ho-labeled microspheres for
      possible use in radioembolic therapy of liver cancer.
AB  - Hepatocellular carcinoma (HCC) or liver cancer is an increasingly prevalent and
      highly morbid disease with critical significance in the Asian and African
      subcontinents. Among the various therapies currently used in the clinic to combat
      the global menace of HCC, radioembolization with suitable therapeutic isotopes is
      an effective targeted approach. In the Indian context, the significant cost and
      logistical disadvantage of imported radioembolic formulations for HCC therapy
      make it essential to develop more feasible indigenous alternatives-using locally
      available radioisotopes and microspheric carriers-that can serve the nuclear
      medicine community. With this aim Ho-166 was produced with good specific activity
      (>13 GBq mg-1 ) and purity (>99%) by reactor irradiation. Various commercially
      available microspheres were labeled with this therapeutic radioisotope,
      characterized for yield and stability of the radiolabeling, and tested for their
      in vivo retention and stability in Wistar rat model by viable surgery. Under the
      optimized reaction conditions, 166 Ho-labeled microspheres were prepared with
      high yield (>94%-99%) and in vitro stability (>95%) in saline and serum.
      Retention studies in animal model showed that 166 Ho-labeled microspheres
      remained stable in vivo and showed excellent retention in the site of interest
      (~95% at 72-hour p.i.). The study indicates good potential and warrants further
      investigation for application of these indigenous radiolabeled microspheres for
      HCC therapy. The successful application of this technology in the clinic would
      lead to logistically advantageous and cost-effective indigenous alternatives to
      expensive imported therapeutic solutions.

PMID- 29462502
TI  - Therapeutic Drug Monitoring of Biologics for Inflammatory Bowel Disease: An
      Answer to Optimized Treatment?
AB  - Therapeutic drug monitoring (TDM), or the measurement of drug concentrations in
      blood and antidrug antibodies, for biologic therapies used to treat inflammatory
      bowel disease (IBD) is an area of growing interest within the IBD community. When
      there is a definable relationship between drug concentration and clinical effect,
      blood concentration of biologics (and antidrug antibodies assessment) could be
      used to predict patient response and to titrate the biologics to maximize
      therapeutic benefit. This dose individualization has been proven to be more
      efficacious and cost-effective than empiric dose adjustment and can better guide
      therapeutic decisions regarding therapy withdrawal or switch. Appropriate
      implementation and interpretation of drug concentration measurement in TDM are
      essential to ensure full clinical benefit. Factors that need to be considered
      include sources of variability, timing of blood sampling, dosing history,
      analytical performance, immunogenicity, comedications, and clinical status of the
      patients. Desired target concentrations for biologics used in IBD have not been
      clearly determined yet. Published concentration thresholds differed widely for a
      given biologic, indicating a lack of consistent information. Factors other than
      drug concentration that may contribute to the dose-response variation are largely
      missing in the current TDM setting. A target range is likely preferable to a
      single value for TDM of biologics in IBD, and additional prospective research
      needs to be conducted in order to establish these ranges. Moving forward, TDM may
      be combined with pharmacodynamic end points and modeling and simulation tools for
      improved therapeutic benefit in IBD.

PMID- 29462504
TI  - Customizing the Electrochemical Properties of Carbon Nanodots by Using Quinones
      in Bottom-Up Synthesis.
AB  - We show how the redox potentials of carbon nanodots (CNDs) can be modulated by
      employing quinones as electroactive precursors during a microwave-assisted
      synthesis. We prepared and characterized a redox library of CNDs, demonstrating
      that this approach can promote the use of carbon nanodots for ad hoc
      applications, including photocatalysis.

PMID- 29462505
TI  - Neutrophil heterogeneity: Bona fide subsets or polarization states?
AB  - Neutrophils are key components of the innate immune system that play important
      roles during infection, injury, and chronic disease. In recent years, neutrophil
      heterogeneity has become an emerging focus with accumulating evidence of
      neutrophil populations with distinct functions under both steady-state and
      pathologic conditions. Despite these advances, it remains unclear whether these
      different populations represent bona fide subsets or simply
      activation/polarization states in response to local cues. In this review, we
      summarize the varied neutrophils populations that have been described under both
      basal and during inflammation. We discuss the evidence that supports the
      existence of neutrophils subsets. Finally, we identify potential gaps in our
      knowledge that may further advance our current understanding of neutrophil
      heterogeneity.

PMID- 29462503
TI  - Efficacy of a Spanish-Language Self-Administered Stress Management Training
      intervention for Latinas undergoing chemotherapy.
AB  - BACKGROUND: Cancer patients often report increased stress during chemotherapy.
      Stress management training has been shown to reduce this adverse outcome, but few
      interventions exist for Spanish-speaking Hispanic and Latina women (Latinas).
      METHODS: Following community feedback (including focus groups/in-depth
      interviews), we transcreated the Spanish-Language Self-Administered Stress
      Management Training (SL-SAT) intervention based on our previously developed and
      implemented English-based intervention. Latinas about to begin chemotherapy were
      randomized to SL-SAT (n = 121) or usual care (n = 119). A Spanish-speaking
      interventionist met with SL-SAT participants who received the SL-SAT toolkit
      containing instructions in 3 well-established stress management techniques (deep
      breathing, progressive muscle relaxation and guided imagery, and use of coping
      self-statements). Usual care participants received an educational booklet about
      coping with chemotherapy. All patients were instructed by nurses on their
      chemotherapy medications and given a resource listing of local support groups.
      Outcomes were obtained at baseline, and 7 and 13 weeks after starting
      chemotherapy. Primary outcomes included anxiety and depression, cancer-related
      distress, emotional well-being, and spiritual well-being. Secondary outcomes
      included functional well-being, social/family well-being, physical well-being,
      symptom severity, and self-efficacy for managing stress. Data were analyzed by
      using mixed models. RESULTS: In both groups, improvements were observed in
      emotional well-being (P = .01), and declines were observed in functional well
      being (P = .05), and physical well-being (P < .0001). Symptom severity increased
      across the follow-up period (P < .001). CONCLUSIONS: To be effective, stress
      management interventions for Latinas receiving chemotherapy may necessitate more
      attention from an interventionist, delivery of the intervention over a longer
      interval, and/or a group-based format.

PMID- 29462507
TI  - The HOPE Asia Network for "zero" cardiovascular events in Asia.

PMID- 29462506
TI  - Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in
      Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.
AB  - The majority of United States kidney transplant patients are treated with
      tacrolimus, a drug effective in preventing graft rejection, but with a narrow
      therapeutic range, necessitating close monitoring to avoid increased risks of
      transplant rejection or toxicity if the tacrolimus concentration is too low or
      too high, respectively. The trough drug concentration tests are time sensitive;
      patients treated on a twice-daily basis have blood draws exactly 12 hours after
      their previous dose. The schedule's rigidity causes problems for both patients
      and health care providers. Novel once-daily tacrolimus formulations such as LCPT
      (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North
      Carolina) have allowed for blood draws on a once-daily basis; however, even that
      schedule can be restrictive. Results from tests taken either before or after that
      24-hour target time may be discarded, or worse, may lead to inappropriate dose
      changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial
      (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may
      allow for a therapeutic monitoring window that extends for 3 hours before or
      after the 24-hour monitoring target. Furthermore, important tools to help
      clinicians interpret these levels, such as formulas to estimate the 24-hour
      trough level if an alternative monitoring time is used, were constructed from
      these data. These study results give treating clinicians access to data that
      allow them to safely use and monitor LCPT in their patients and expand the body
      of evidence surrounding differentiation and practical application of the novel
      LCPT tacrolimus formulation.

PMID- 29462508
TI  - Comparative effectiveness of an angiotensin receptor blocker, olmesartan
      medoxomil, in older hypertensive patients.
AB  - The efficacy and safety of olmesartan medoxomil (OM) vs active control (AC)
      monotherapy among elderly patients aged 60-79 years (N = 4487) was evaluated by
      meta-analysis (25 studies). In all patients, change from baseline to end point in
      blood pressure (BP) was significantly greater with OM vs AC (-19.5/-11.9 vs 
      16.8/-10.7 mm Hg). Greater proportions of OM- vs AC-treated patients achieved BP
      goals. In patients with impaired renal function (estimated glomerular filtration
      rate <60 mL/min/1.73 m2 ), OM treatment resulted in a greater mean change from
      baseline in systolic BP vs AC (-21.2 vs -18.7 mm Hg, respectively) and a greater
      proportion of patients achieving BP goals. These parameters were similar in both
      groups for elderly patients with diabetes. OM was well tolerated with few adverse
      events. OM monotherapy can be used as an initial treatment for hypertension in
      elderly patients, including those with renal impairment or diabetes.

PMID- 29462509
TI  - Theory Uncovers the Role of the Methionine-Tyrosine-Tryptophan Radical Adduct in
      the Catalase Reaction of KatGs: O2  Release Mediated by Proton-Coupled Electron
      Transfer.
AB  - Catalase-peroxidases (KatGs) are bifunctional enzymes exhibiting both peroxidase
      and substantial catalase activities. It is widely recognized from experiments
      that the catalatic activity of KatGs is correlated with a unique covalent adduct
      (M-Y-W) formed in the active site, but the exact role of this adduct was elusive
      up to now. Here, quantum mechanical/molecular mechanical (QM/MM) calculations and
      QM/MM metadynamics are employed to elucidate the molecular mechanism and the role
      of M-Y-W adduct in the catalase reaction. It is shown that O2 formation proceeds
      through a mechanism involving proton-coupled electron transfer (PCET). The M-Y-W
      cation radical adduct, which is close to the heme, His112 and the HOO. radical
      intermediate, acts as an electron sink during the PCET process. The present study
      also highlights the structural differences and functional similarities between
      KatGs and monofunctional catalases.

PMID- 29462510
TI  - Dioxygen Sensitivity of [Fe]-Hydrogenase in the Presence of Reducing Substrates.
AB  - Mono-iron hydrogenase ([Fe]-hydrogenase) reversibly catalyzes the transfer of a
      hydride ion from H2 to methenyltetrahydromethanopterin (methenyl-H4 MPT+ ) to
      form methylene-H4 MPT. Its iron guanylylpyridinol (FeGP) cofactor plays a key
      role in H2 activation. Evidence is presented for O2 sensitivity of [Fe]
      hydrogenase under turnover conditions in the presence of reducing substrates,
      methylene-H4 MPT or methenyl-H4 MPT+ /H2 . Only then, H2 O2 is generated, which
      decomposes the FeGP cofactor; as demonstrated by spectroscopic analyses and the
      crystal structure of the deactivated enzyme. O2 reduction to H2 O2 requires a
      reductant, which can be a catalytic intermediate transiently formed during the
      [Fe]-hydrogenase reaction. The most probable candidate is an iron hydride
      species; its presence has already been predicted by theoretical studies of the
      catalytic reaction. The findings support predictions because the same type of
      reduction reaction is described for ruthenium hydride complexes that hydrogenate
      polar compounds.

PMID- 29462513
TI  - Mind the GAP, for Tolerance to Gut Bacteria.

PMID- 29462512
TI  - Recommendations of the Advisory Committee on Immunization Practices for use of
      herpes zoster vaccines.

PMID- 29462511
TI  - Financial difficulty, worry about affording care, and benefit finding in long
      term survivors of cancer.
AB  - OBJECTIVE: To examine the associations of worry about affording care and
      reporting financial difficulties with benefit finding in long-term cancer
      survivors. METHODS: Long-term survivors of cancer (n = 547) in 3 integrated
      health care delivery systems completed the Medical Expenditure Panel Survey
      Cancer Survivorship Supplement. The relationship between benefit finding
      (becoming a stronger person, coping better, and making positive changes) and the
      potentially interacting factors of worry about affording care and financial
      difficulties was examined using multivariate logistic regression models. RESULTS:
      Of the total sample, 20% reported worry and 15% reported financial difficulty.
      Among those who reported no worry, financial difficulty was positively associated
      with becoming a stronger person (odds ratio [OR] = 2.89, 95% CI: 1.07, 7.80).
      Coping better was not associated with worry, financial difficulties, or the
      interaction of the two. Among those with no financial difficulty, worry was
      positively associated with making positive changes (OR = 2.64, 95% CI: 1.41,
      4.96), and among those reporting no worry, financial difficulty had a non
      significant positive association with making positive changes (OR = 1.98, 95% CI:
      0.91, 4.31). Among those reporting worry, having financial difficulties was
      associated with lower odds of making positive changes (OR = 0.32, 95% CI: 0.13,
      0.78). CONCLUSIONS: Our results suggest a complex relationship between financial
      difficulty, worry, and benefit finding. The combination of worry about affording
      care and financial difficulty needs to be addressed and further studied among
      cancer survivors, as the presence of both, but not alone, was negatively
      associated with making positive changes, an aspect of benefit finding.

PMID- 29462514
TI  - Building a Transplantation Team with Advanced-Practice Providers.

PMID- 29462515
TI  - Risk Factor for Diabetes Mellitus and High Blood Glucose With HMG-CoA Reductase
      Inhibitors Using a Postmarketing Surveillance Database in Japan.
AB  - To investigate whether 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor
      (statin) use is associated with an increased risk of diabetes mellitus and
      hyperglycemia, we performed a nested case-control study using a postmarketing
      surveillance database in Japan. The database cohort included 26,849 cases of
      statin use and 5308 cases of other lipid-lowering drug use in patients with
      hyperlipidemia. Participants received at least 1 type of statin, had a clear
      medication history of statin use, and had no complications of diabetes mellitus.
      Cases were defined as onset of diabetes mellitus or hyperglycemia during statin
      intake. For each case, 20 controls were randomly selected and matched by time
      point. The factors associated with an increased risk of diabetes mellitus and
      hyperglycemia during statin intake examined included sex, age, body mass index,
      statin use duration, complications, concomitant medication, and clinical
      laboratory tests. Statin-associated diabetes mellitus or hyperglycemia was
      identified based on abnormal elevation of blood glucose concentrations beyond the
      reference range. A total of 19,868 patients met the inclusion criteria, of whom
      24 were patients in the case group. Two complicating factors, fatty liver
      (adjusted odds ratio 16.10) and hyperuricemia (adjusted odds ratio 28.96), were
      extracted for onset of diabetes mellitus or hyperglycemia. Nonalcoholic fatty
      liver was associated with diabetes mellitus, obesity, and insulin resistance, and
      hyperuricemia was associated with lifestyle. This study suggested that the onset
      of diabetes mellitus or hyperglycemia might be increased with statin use in
      patients with complications of fatty liver and hyperuricemia.

PMID- 29462516
TI  - Addressing Youth Violence in the Primary Health Care Setting.

PMID- 29462517
TI  - Violence and Mental Health: Trauma-Informed Practice and Wellness Approach to
      Violence Victimization.

PMID- 29462518
TI  - Adolescent Relationship Abuse and Sexual Violence Prevention and Intervention:
      The Role of the Physician.

PMID- 29462519
TI  - Social Media as a New Venue for Aggression and Bullying.

PMID- 29462520
TI  - The Influence of Violent Media on Aggression in Adolescents.

PMID- 29462521
TI  - Substance Use and Violence: Co-Occurrence and Strategies for Intervention.

PMID- 29462522
TI  - Promoting Resilience in Youth Who Are Violence-Involved.

PMID- 29462523
TI  - Addressing Firearm Violence in the Primary Health Care Setting.

PMID- 29462524
TI  - Building an Evidence-Based Multi-Tiered System of Supports for Violence
      Prevention in the Health Care Setting.

PMID- 29462525
TI  - Treating Youth Violence in Hospital and Emergency Department Settings.

PMID- 29462526
TI  - Essential professional duties for the sub-Saharan medical/dental graduate: An
      Association of Medical Schools of Africa initiative.
AB  - BACKGROUND - Globally, human resources for health are being optimized to address
      the increasing health burden and concomitant increased demands on health
      professionals. These demands are even more exacting in Sub-SaharanAfrica
      considering the shortage of health care workers, especially physicians. The
      noteworthy efforts at deploying task-shifting to address this situation not
      withstanding, the situation also signals the need to re-define the objectives of
      medical instruction to ensure effective and contemporary medical practice in a
      mostly physician-led health workforce across the sub-continent. In this regard,
      medical and dental graduates must be educated to perform certain minimum
      essential professional duties competently. Essential Professional Duties are
      locally relevant professional activities of international standard that represent
      identifiable outcomes against which the effectiveness of physicians in a specific
      community can be measured to ensure social accountability. PROCEDURE AND PRODUCT 
      The Association of Medical Schools of Africa has developed the 'Essential
      Professional Duties for sub-Saharan medical and dental graduates' to ensure these
      physicians provide safe and effective contemporary medical/dental practice on the
      sub-continent. The duties have been grouped into those required for basic patient
      care, basic administrative skills, basic emergency care, communication, inter
      professional relationships, self-directed learning and social responsibilities.
      Their relevance and suitability have been evaluated prior to their adoption by
      the Association. CONCLUSION; These Essential Physician Duties have been developed
      to serve as targets for health professionals training instruments and thus give
      direction to health system strategies. It is hoped that they will be adopted by
      medical and dental schools across sub-,. Saharan Africa.

PMID- 29462527
TI  - Dealing with diabetes-specific emotional distress: A cross-sectional survey of
      physical activity option.
AB  - BACKGROUND: Diabetes-specific emotional distress is common among people with type
      2 diabetes due to the complexities associated with care and maintenance of
      wellness among the patients. Unlike the focus on glycaemic control, literature
      appears unavailable about how physical activity may help in the control of
      diabetes-specific emotional distress. This study was conducted to investigate the
      link between diabetes- specific emotional distress and physical activity.
      METHODOLOGY: Type 2 diabetes patients (n = 206) were enrolled into this study
      from two major health care facilities in Ibadan, Southwestern Nigeria. Physical
      activity was assessed using the International Physical Activity Questionnaire
      while diabetes-specific emotional distress was assessed using the Problem Areas
      in Diabetes Questionnaire. Data were analysed using descriptive and inferential
      statistics at +/- 0.05. RESULTS: The participants' mean age was 58.6 12.7 years
      with 109 (52.9%) reporting low physical activity levels and 182 (88.3%) reporting
      varying degrees of diabetes- specific emotional distress. Compared to
      participants with low physical activity, those who reported moderate-to- vigorous
      physical activity reported a reduced risk of diabetes-specific emotional distress
      (OR = 0.53; 95% CI = 0.26-0.82). Age, sex and level of education were not
      associated with the distress. CONCLUSIONS: A substantial proportion of patients
      with type 2 diabetes reported low physical activity levels and much more reported
      diabetes-specific emotional distress. Those who reported moderate-to-vigorous
      physical activity reported a significantly lower risk of diabetes-specific
      emotional distress. Reduction in. the risk of diabetes-specific emotional
      distress may be yet another strong point in advocacy for physical activity among
      patients with type 2 diabetes.

PMID- 29462528
TI  - Changes in kidney function and oxidative stress biomarkers in offspring from dams
      treated with dexamethasone during lactation in Wistar rats.
AB  - BACKGROUND: The effects of maternal exposure to glucocorticoids during gestation
      on various organs in the offspring have been reported in literature. There is
      paucity of information on the effects of maternal glucocorticoids treatment
      during lactation on organ functions in the offspring. The present study was
      designed to investigate the changes in kidney function and oxidative stress
      biomarkers in offspring of dams treated with dexamethasone during lactation in
      Wistar rats METHODS: Twenty pregnant rats (180-200g) were divided into 4 groups
      (n=5). Group I was administered 0.02ml/100g/day of normal saline (subcutaneously,
      s.c) at lactation days 1-21 (control). Groups 2,3, and 4 were administered 100
      MU/kg/day dexamethasone (Dex) (s.c) at lactation days 1-7 (Dexl-7),1-14(Dexl-14),
      and 1-21(Dexl-21) respectively. Evaluation of serum creatinine, urea and markers
      of oxidative stress in the kidney and histopathology of the kidney were carried
      out at 12 weeks of postnatal life. RESULTS: Serum creatinine and urea levels
      were. significantly (p<0.05) higher in the Dexl-7, DexI-14and Dexl-21 when
      compared with the control. Kidney MDA level was also significantly (p<O.05)
      increased in the Dexl-7, Dexl-14 and Dexl-2lgroups when compared with the
      control. Kidney SOD activities, catalase activities and protein in the treatment
      groups Dexl-7, Dexl-14 and Dexl-21 were all significantly (p<0.05) lower than the
      control. Histology of the kidney showed mild, moderate and severe tubular
      necrosis in the Dexl-7, Dexl-14 and Dexl-21 groups respectively. CONCLUSION:
      Results suggest that maternal exposure to dexamethasone during lactation may lead
      to increase oxidative stress in the kidney and increase renal necrosis.

PMID- 29462529
TI  - Accuracy of non-endoscopic predictors of oesophageal varices in liver cirrhosis
      using platelet count, splenic size and portal vein diameter.
AB  - BACKGROUND: Endoscopy has been recommended for all patients with liver cirrhosis
      to detect varices, but it is expensive, invasive and uncomfortable. There is
      therefore, need to find non-endoscopic means to predict oesophageal varices. AIM:
      To determine the sensitivity and specificity of platelet count, splenic size and
      portal vein diameter to predict oesophageal varices in patients with liver
      cirrhosis. METHODOLOGY: Subjects were patients with liver cirrhosis and controls
      without liver disease aged 18 years and above. Platelet count was determined
      using Mindray BC-3000plus auto-analyzer. Portal vein diameter was measured at a
      point where it crosses the hepatic artery. Splenic length was measured through
      the hilum, as the distance between the dome and the tip. All the patients had
      upper gastrointestinal endoscopy. Varices were graded into I,II, III based on the
      Japanese classification of oesophageal vatices. RESULTS: The patients comprised
      59 (81%). males and 14 (19%) females, while controls comprised 29 (73%) males and
      11 (27%) females. The mean+/-(S.D.) age of the patients and controls was 44+/
      12.6 and 40+/- 13 years respectively. There was statistically significant
      difference in the means of platelet count and platelet count/splenic size between
      patients with large oesophageal varices and those with small or no varices
      (p=0.00), while no such difference in the means of splenic size, portal vein
      diameter and the presence/size or absence of varices. (p=0.06). CONCLUSION:
      Platelet count has the best sensitivity and specificity among the three values in
      predicting both small and large varices in patients with liver cirrhosis.

PMID- 29462530
TI  - Neuroprotective effects of kolaviron against psycho-emotional stress induced
      oxidative brain injury in rats: The whisker removal model.
AB  - BACKGROUND: The study investigated the neuroprotective potentials of kolaviron (a
      biflavonoid complex of Garcinia kola) against psycho-emotional stress induced
      oxidative brain injury in Wistar rats. METHODS: Twenty-four adult Wistar rats
      (180-220g) randomly divided into four groups (1-1V,n=6) were used for the study .
      Group 1 served as control (non stressed), group 11 consisted of stressed rats
      induced by complete removal' of the whiskers around the mouth and the nose
      without anaesthesia. The rats in group 111 were pre- treated with 200mg/kg
      kolaviron per oral (p.o), daily for seven days before being subjected to the
      stress procedure' while group 1V rats also had 200mg/kg oral kolaviron alone
      without being stressed. The animals were later euthanized by cervical
      dislocation, cerebellum and frontal cortex removed and then subjected to
      biochemical and histopathological analysis. RESULTS: Whisker removal
      significantly(p<0.05) increased lipid peroxidation (U/mg protein) in the
      cerebellum (3.82+/-0.22 vs 6.50+/-0.41) and the cerebral cortex (14.57+/-2.50 vs
      30.11+/- 4.70) compared with their controls, it also produced significant
      reductions 'in catalase activities (U/min/mg protein) in cerebellum (169.65+/
      11.02 vs 87.72, p <0.001) and the cerebral cortex (264.5 +/- 40.57 vs 122.71 +/-
      15.70,p< 0.001). Glutathione levels (U/mg protein) were similarly significantly
      (P<0.001) reduced in both cerebellum (132.40 +/- 4.81 vs 37.60 +/- 1.50) and the
      cerebral cortex (370.42 +/-20.51 vs 120.51+/- 25.35) compared with their
      corresponding controls. There were also histological abnormalities like cellular
      degeneration and necrosis in both the frontal cortex and the cerebellum of the
      stressed rats. Pre- treatment with kolaviron not only reversed these biochemical
      alterations but also significantly attenuated these observed histopathological
      changes. CONCLUSION: The present study demonstrated the neuroprotective potential
      of kolaviron against psycho-emotional stress-induced oxidative brain injury
      through the inhibition of oxidative stress.

PMID- 29462531
TI  - Constraints in the neurosurgical management of pituitary tumours in an African
      developing country: a 5-year observational study from Benin Republic.
AB  - INTRODUCTION: Benin Republic, a very low-income-sub- Saharan African developing
      country, has a severely resource-constrained health system. There is hardly any
      data available on the pattern of pituitary tumour in this country METHODS: A
      single surgeon, hospital-based retrospective analysis of the pattern,
      presentation and clinical / surgical course of7a prospective cohort of pituitary
      tumours seen over a 5-year period is presented RESULTS: There were 38 cases, 20
      (52.6%) female; 27% of all brain tumours seen. They were macroadenomas in 97. 4%,
      and greater than 4cm in 63.2%. They occurred mainly (86.8%) in people aged 15 to
      59 years. Delayed neurosurgical presentation, mean 5.16years (range 1-23years)
      was the rule in 94.7%%; and, visual and endocrinological dysfunction the two most
      prominent symptomatology. Due to severe logistic constraints, neuroimaging
      evaluation was possible with cranial CT only in about 90% of the cases. Also only
      9 cases (23.7%) did eventually receive the planned neurosurgical operative
      treatment, in 5 cases of which even this surgical treatment Was only facilitated
      by some foreign neurosurgical missions. CONCLUSIONS: Pituitary adenomas represent
      a sizeable proportion of brain tumours in Benin Republic. National health care
      resources in this low income African country for their optimal clinical /
      radiological evaluation, and surgical treatment, are grossly inadequate; indeed,
      almost non-existent.

PMID- 29462532
TI  - Functional health of patients with knee osteoarthritis in a family medicine
      clinic in Ibadan.
AB  - BACKGROUND: Patients with knee osteoarthritis experience pain and functional
      impairment, which impacts upon activities of daily living ultimately leading to a
      loss of functional independence and low quality- of-life. This study therefore
      aimed at evaluating the functional health status of patients with knee
      osteoarthritis in the Family Medicine clinic, University College Hospital,
      Ibadan, Nigeria. METHODS: A cross-sectional study was conducted on 270 eligible
      respondents between January and March 2011. The Ibadan Knee/Hip Osteoarthritis
      Measure (IKHOAM) was administered after screening with the knee pain screening
      tool (KNEST). Respondents'Socio- demographic characteristics and knee pain
      intensity ratings were also recorded. RESULTS: The age range of respondents in
      the study was from 28 years to 85 years with a female: male ratio 5:1. Out of the
      270 respondents studied, 146 (54.1%) reported restriction in performing duties at
      work. One hundred and twenty seven respondents (47.0%) needed some assistance in
      walking outside the house for 15 to 20 minutes, whilst 195 (72.2%) required some
      assistance in climbing stairs. Thirty four (12.6%) of Muslims and 77 (28.5%) of
      Christians could not kneel to pray. Males are twice more likely to have a better
      functional health than females (OR= 2.1, 95% CI= 1.0- 4.6, p=0.046). CONCLUSION:
      Knee osteoarthritis significantly impairs activities of daily living, especially
      some socio-cultural and religious practices of respondents. Therefore in addition
      to treating the knee symptoms, removing environmental barriers may reduce
      immobility within and outside the home thereby improving functionality.

PMID- 29462533
TI  - Awareness and distribution of ABO, Rhesus blood groups and haemoglobin phenotypes
      among medical undergraduates in a Nigerian university.
AB  - BACKGROUND: In the past two decades the Nigerian government and religious
      organisations have put more emphasis on knowing the haemoglobin electrophoresis
      of school children and intending couples respectively. Knowledge of the
      distribution of blood groups and haemoglobin electrophoretic patterns among young
      people is vital for the prevention of haemoglobinopathies in the population and
      for providing effective blood banking services. Therefore, this study was
      designed to assess the frequency and awareness of blood group and
      haemoglobinphenotypes among a new set of fourth year clinical medical and dental
      students of the University of Ibadan, Nigeria. METHODS: Data, including socio
      demographics, self- reported blood group and haemoglobin phenotypes, were
      obtained from 155 students using a self-administered questionnaire. The ABO,
      Rhesus (Rh) blood groups and haemoglobin electrophoresis were determined by the
      tile (slide) technique and cellulose acetate at alkaline phrespectively. RESULTS:
      Only 43.9% of the participants knew their blood groups while less than a third
      (29.7%) knew their haemoglobin phenotypes. knowledge of both their blood groups
      and haemoglobin phenotypes was documented in as low as 20.6% of the respondents.
      The frequency of haemoglobin AA, AS, AC and. CC were 78.0%, 16.8%, 3.9% and 1.3%
      respectively. Similarly, the distribution of blood groups were: 0 RhD positive -
      47.8%;0 RhD negative- 1.9%;ARhD positive- 21.9%; A RhD negative - 1.3%; B RhD
      positive - 23.2%; B RhD negative -1.3% and AB RhD positive - 2.6%. No participant
      was AB RhD negative. Participants who bad previously donated blood and those who
      were females were more likely to know their blood groups and haemoglobin
      phenotypes respectively (p<0.05). CONCLUSION: Awareness of blood groups and
      haemoglobin phenotypes among the medical and dental students was poor.
      Documentation and routine screening for haemoglobinphenotypes as well as blood
      grouping, accompanied by appropriate counseling should be institutionalised in
      Nigeriantertiary institutions.

PMID- 29462534
TI  - Knowledge and attitude of sexually transmitted diseases among adolescents in
      Ikeji-Arakeji, Osun State, in South-Western Nigeria.
AB  - BACKGROUND: Globally, sexually transmitted disease (STD) is a public health
      problem. In Nigeria, adolescents form a substantial proportion (22%) of the
      population and are particularly prone to STDs because of the influence of peer
      pressure and urge to experiment sexual activity. The study examined the knowledge
      and attitude of adolescents towards the prevention of sexually transmitted
      diseases. METHOD: The survey study was descriptive cross- sectional and carried
      out among consenting secondary school students aged 10-24 years completing a self
      administered questionnaire on knowledge and attitude in relation to sexually
      transmitted diseases in Ikeji- Arakeji, Oriade Local government, Osun State,
      Nigeria. The proportionate sampling technique was used to recruit 341
      participants into the study. Data were analyzed using descriptive and inferential
      statistics. RESULTS: Male-Female distributions were 46.3% and 53.7% respectively.
      Mean age at first sex (sex initiation) was 16.8 years (approximately 17years) and
      about 97% of the respondents knew about STDs. The media/ magazine was the major
      source of information about STDs, accounting for more than half (57%) of the
      responses on sources of STD information followed closely from that from friends
      with 31%. Parent's source of information was about 11%. Knowledge of STDs centred
      mainly on HIV/AIDS with 83% and there was a poor knowledge (78%) of its symptoms.
      About 40% of all respondents had initiated sex at the time of the study and 46%
      of the adolescents, as against 54%, thought it was bad to initiate sex before
      marriage. There was a significant association between perception about initiating
      sex before marriage and ever having sex using bivariate analysis x(2)=268.4,
      P<0.001). Also, there was a significant difference between the different groups
      (sources of information) in influencing sex initiation (F=318.47 and P=0.000).
      Post-hoc analysis showed that each of the different groups (sources of
      information) was distinct. CONCLUSION: Adolescents' knowledge of STDs generally
      limited to HIV/AIDS and perception about sex significantly influenced the
      decision to initiate sex. There is, therefore, a serious need to implement sexual
      education and other sexual and reproductive health interventions early for
      adolescents in Nigeria.

PMID- 29462535
TI  - Zinc salt enhances gastroprotective activity of risperidone in indomethacin
      induced gastric ulcer.
AB  - BACKGROUND: Zinc has been reported to mediate cellular responses to injury by
      producing cytoprotection via the scavenging of reactive oxygen species. Anti
      stress medications are generally anti-psychotic drugs and anti- depressants. Some
      Anti-psychotic drugs such as risperidone have been reported to possess anti-ulcer
      activity. Risperidone as an antipsychotic drug blocks several neurotransmitter
      systems including dopaminergic, adrenergic, histaminergic and serotonergic
      pathways. METHOD: The study investigated the antiulcer activity of Zinc Chloride
      (ZnCl(2)) in combination with risperidone in male Wistar rats. The animals were
      divided into two groups of twenty animals each for ZnCl(2) and risperidone
      groups. Each group was further divided into four subgroups. ZnCl(2) was
      administered orally at 20mg/kg, 40mg/kg and 80mg/kg to a subgroup, while 80mg/kg
      of ZnCl(2) was administered in combination with risperidone (0.1mg/kg, 0.3mg/kg
      and 0.5mg/kg) orally once daily for 21 days. The controls were treated with
      distilled water. Ulcer was induced using indomethacin. Histology of the stomach
      tissues was prepared with PAS and H& E stains. Ulcer score and ulcer area were
      assessed using standard methods. Data were analysed using student t-test and
      Graphpad Prism 5. RESULTS: There were decreases in ulcer scores using the
      different doses of ZnCl, (20mg/kg, 40mg/kg and 80mg/kg). Also using the highest
      dose ZnCl(2) (80mg/ kg) and different doses of risperidone there were decreases
      in ulcer scores compared to the control. This effect of the risperidone showed a
      significant dose- dependent reduction. The effect ZnCl(2), and risperidone were
      also reflected in the ulcer area and in the histology. CONCLUSION: These findings
      suggest that ZnCl(2), enhances the gastroprotective activity ofrisperidone in
      indomethacin- induced gastric ulcer. However, more detailed studies are necessary
      to confirm the relevance of this finding and its implications in clinical
      settings.

PMID- 29462536
TI  - Type 1 diabetes mellitus and Graves' disease in Down's syndrome--a rare
      combination.
AB  - BACKGROUND: Autoimmune diseases including thyroid. disorders, type 1 diabetes and
      celiac disease are commoner in persons with Down's syndrome compared with the
      general population. Coexistent type 1 diabetes and hyperthyroidism in Down's
      syndrome is however not commonly reported in literature. OBJECTIVE: To report a
      case of a lady presenting with Graves' disease and type 1 diabetes at the same
      time. CLINICAL PRESENTATION: We report the case of a 22- year-old lady with
      Down's syndrome who presented with weight loss, polyuria and polydipsia. Physical
      examination revealed typical dysmorphicfacies of Down's syndrome and a goitre.
      Laboratory data revealed hyperglycaemia (random plasma glucose-331 mg/dl). She
      also had biochemical evidence in keeping with hyperthyroidism and markedly
      elevated thyroid peroxidase antibodies (>1087.0 IU/ml). She improved after
      rehydration, insulin therapy and antithyroid drugs. CONCLUSION: Coexisting
      autoimmune diseases may present in patients with Down's syndrome. We advocate for
      routine screening for diabetes and thyroid dysfunction in ersons with Down's
      syndrome.

PMID- 29462538
TI  - Egg-guarding behavior of the treehopper Ennya chrysura (Hemiptera: Membracidae):
      female aggregations, egg parasitism, and a possible substrate-borne alarm signal.
AB  - Treehoppers are known for their substrate-borne communication and some of them
      also for their subsocial behavior. Following a more general study of the natural
      history and substrate-borne signal repertoire of the treehopper Ennya chrysura,
      the objective of this paper was to explore in greater depth the signals and other
      behaviors associated specifically to egg-guarding. Theese were studied both in
      natural and laboratory conditions between July, 2000 and March, 2004. The spacial
      distribution of egg guarding females was studied in the natural population;
      recording equipment and playback experiments were used in the laboratory and then
      analyzed digitally. Under natural conditions (San Antonio de Escazu, Costa Rica),
      female E. chrysura guard their egg masses and egg-guarding was associated with
      lower parasitism of the eggs from the wasps Gonatocerus anomocerus and
      Schizophragma sp. (Mymaridae). Females tended to place their eggs close to other
      egg-guarding females and they produced substrate-borne vibrations when disturbed.
      An aggregated pattern under natural conditions was confirmed by calculating
      dispersion indices from egg-clutch data obtained from 66 leaves in the field. The
      disturbance signal was characterized from laboratory recordings of substrate
      borne vibrations of 10 egg-guarding females. Experiments conducted in the
      laboratory with 18 egg-guarding females showed that those which were previously
      exposed to the disturbance signal of another female moved slightly or vibrated
      more during playbacks and that they reacted more quickly and exhibited more
      deffensive behaviors in response to a tactile stimulus. The signals produced
      while defending against egg parasites may therefore function as an alarm and
      favor aggregating behavior of egg-guarding females.

PMID- 29462537
TI  - [In vitro antibacterial activity of Curcuma longa (Zingiberaceae) against
      nosocomial bacteria in Monteria, Colombia].
AB  - Bacterial resistance is a growing health problem worldwide that has serious
      economic and social impacts, compromising public health, and the therapeutic
      action of current antibiotics. Therefore, the search for new compounds with
      antimicrobial properties is relevant in modern studies, particularly against
      bacteria of clinical interest. In the present study, in vitro antibacterial
      activity of the ethanol extract and essential oil of Curcuma longa
      (Zingiberaceae) was evaluated against nosocomial bacteria, using the
      microdilution method. Escherichia coli strains, Pseudomonas aeruginosa,
      Klebsiella pneumoniae, Proteus sp. were used, Salmonella sp. and Bacillus sp.,
      isolated from nosocomial infections in a hospital in the city of Monteria and
      reference strains of S. aureus ATCC 43300, S. aureus ATCC 29213, S. aureus ATCC
      25923, P. aeruginosa ATCC 27853, E. coli ATCC 25922 and K. pneumonia ATCC 700603.
      The ethanol extract antibacterial profile was more efficient at higher
      concentrations (1 000 ppm), obtaining significant percentages of reduction of
      more than 50 % against K. pneumoniae ATCC 700603 and a clinical isolate of E.
      coli; while compared to Bacillus clinical isolate, was more active than the
      essential oil. For the rest of microorganisms, the reduction percentages obtained
      at a concentration of 1 000 ppm varied between 17 and 42 % with ethanolic
      extract, and 8 to 43 % with essential oil. At concentrations of 100 and 500 ppm
      antibacterial activity of the extracts was lower. The results indicated that the
      ethanolic extract and essential oil of C. longa rhizomes have active compounds
      with antibacterial properties that could be used in future research as a
      therapeutic alternative for the treatment of infections caused by nosocomial
      pathogens.

PMID- 29462539
TI  - Bibliometry of the Revista de Biologia Tropical / International Journal of
      Tropical Biology and Conservation: document types, languages, countries,
      institutions, citations and article lifespan.
AB  - The Revista de Biologia Tropical / International Journal of Tropical Biology and
      Conservation, founded in 1953, publishes feature articles about tropical nature
      and is considered one of the leading journals in Latin America. This article
      analyzes document type, language, countries, institutions, citations and for the
      first time article lifespan, from 1976 through 2014. We analyzed 3 978 documents
      from the Science Citation Index Expanded. Articles comprised 88 % of the total
      production and had 3.7 citations on average, lower than reviews. Spanish and
      English articles were nearly equal in numbers and citation for English articles
      was only slightly higher. Costa Rica, Mexico, and the USA are the countries with
      more articles, and the leading institutions were Universidad de Costa Rica,
      Universidad Nacional, Universidad Nacional Autonoma de Mexico and Universidad de
      Oriente (Venezuela). The citation lifespan of articles is long, around 37 years.
      It is not surprising that Costa Rica, Mexico, and Venezuela lead in productivity
      and cooperation, because they are mostly covered by tropical ecosystems and share
      a common culture and a tradition of scientific cooperation. The same applies to
      the leading institutions, which are among the largest Spanish language
      universities in the neotropical region. American output can be explained by the
      regional presence of the Smithsonian Tropical Research Institute and the
      Organization for Tropical Studies. Tropical research does not have the rapid
      change typical of medical research, and for this reason, the impact factor misses
      most of citations for the Revista, which are made after the two-year window used
      by the Web of Science. This issue is especially damaging for the Revista because
      most journals that deal with tropical biology are never checked when citations
      are counted for by the Science Citation Index.

PMID- 29462540
TI  - [Current and future ecological niche of Leishmaniasis (Kinetoplastida:
      Trypanosomatidae) in the Neotropical region].
AB  - The leishmaniasis is a complex disease system, caused by the protozoan parasite
      Leishmania and transmitted to humans by the vector Lutzomyia spp. Since it is
      listed as a neglected disease according to the World Health Organization, the aim
      of this study was to determine the current and future niche of cutaneous and
      visceral leishmaniasis in the Neotropical region. We built the ecological niche
      model (ENM) of cutaneous (N= 2 910 occurrences) and visceral (N= 851 occurrences)
      leishmaniasis using MaxEnt algorithm. Nine bioclimatic variables (BIO1, BIO4,
      BIO5, BIO6, BIO7, BIO12, BIO13, BIO14, BIO15 (downloaded from the Worldclim) and
      disease occurrences data were used for the construction of ENM for three periods
      (current, 2050 and 2070) and four climate change scenarios (RCP 2.6, 4.5, 6.0 y
      8.5). We analyzed the number of pixels occupied, identity niche, modified niche
      (stable, loss, and gain) and seasonality. Our analyses indicated the expansion
      for cutaneous leishmaniasis (CL), a comparison for visceral leishmaniasis (VL).
      We rejected the null hypothesis of niche identity between CL and VL with
      Hellinger's index = 0.91 (0.92-0.98) and Schoener's Index = 0.67 (0.85-1.00) but
      with an overlap niche of 56.3 %. The differences between the two leishmaniasis
      types were detected in relation to RCP scenarios and niche shifts (area gained /
      loss). Seasonality was more important for CL. We provided a current picture of CL
      and VL distributions and the predicted distributional changes associated to
      different climate change scenarios for the Neotropical region. We can anticipate
      that increasing range is likely although it will depend locally on the future
      trends in weather seasonality.

PMID- 29462541
TI  - [Pollen resource and seasonal cycle of Thygater aethiops (Hymenoptera: Apidae) in
      an urban environment (Bogota-Colombia)].
AB  - Thygater aethiops is a native bee that can be found in parks and gardens in
      diverse urban areas such as those in the city of Bogota (Colombia). However,
      little is known about its biology as well as ecological adaptations to urban
      areas. This study aimed to describe the seasonal cycle and daily foraging
      activities of T. aethiops, as well as identify the pollen resources used by this
      bee over a year in a population nesting in an aggregation in the "Parque Nacional
      Enrique Olaya Herrera" in Bogota. Changes in the nest activity were monitored
      weekly by counting the number of active nests in the aggregation between
      December/2012 and February/2014. To determine the daily foraging activity, the
      numbers of bees entering their nests over a period of 10 minutes every hour
      between 8:00 and 14:00 h were recorded. Females with pollen loads entering to
      their nest were captured weekly, between September/2012 and August/2013, and
      their pollen loads analyzed. Three nesting peaks occurred after the precipitation
      peaks, but the number of active nests was not correlated with precipitation. The
      nesting activities stopped in a large number of the active nests (20-50 % of
      nests) after an anthropic disturbance was registered in the nesting area. Bees
      forage for nectar and pollen between 8:00 and 14:00 h, with a peak at 10:00 h.
      Daily foraging activity changed during the study period due to anthropic
      disturbance. There was not a significant relationship between air temperature and
      the number of females entering their nests. Foraging activities did not change
      between the dry and rainy seasons. A total of 26 pollen types were found in 169
      pollen loads. Ulex europaeus (Fabaceae) and Solanum laxum (Solanaceae) were the
      most abundant plants represented on the pollen load across the study period.
      According to these results, T. aethiops would be considered a mesolectic species.
      The ability of T. aethiops to use different pollen resources both native and
      exotic, as well as to presumably recover its population after disturbances, are
      characteristics that may have allowed this bee to adapt to urban environments.
      Knowledge on the floral resources as well as other biological features of this
      bee species is important to promote its conservation in urban areas.

PMID- 29462542
TI  - [Sex ratio and environmental influence on population growth rate of Callinectes
      bellicosus (Decapoda: Portunidae) in the Gulf of California].
AB  - The brown swimming crab (Callinectes bellicosus) is an economically important
      species in the Gulf of California, and its fishing activity, held in Sonora from
      1986, has been affected by a 20-year declining trend in its biomass. With the aim
      to understand the possible reasons of this species population changes along time,
      we estimated population growth rate (r) and sex ratio of C. bellicosus, and
      combined them with three parameters describing its habitat: sea temperature,
      wetland extension and habitat size in four areas along the coast of Sonora. For
      this, monthly mean sex ratio was estimated from crabs samples obtained from
      commercial catches during 1998-2002 and 2012; mean sea surface temperature for
      the spawning period (May-August) were derived from remote sensors for the same
      years; while wetland coverages were obtained from published reports, and habitat
      size was estimated as the fishing surface. For each area, r was estimated using a
      method developed for limited data situations using commercial landings (t) from
      1986-2013. With data from the four areas, simple and multiple linear regression
      models were developed to ascertain theoretical sensitivities of r to variations
      in sex ratio and environmental parameters. A total of 24 556 crabs were sampled;
      males dominated (68.8 %) over females during the study period and in all areas; a
      cluster analysis identified two groups according to sex ratio: a Northern group
      with zones 1 and 2, and a Southern group with zones 3 and 4. r values were
      different in all zones (P<0.001) as was sex ratio (P=0.037); no differences in
      temperature were identified within the study years (P>0.995). Both the estimated
      data and sensitivity analyses suggest the existence of a direct and positive
      dependence of r on the proportion of female crabs and wetland size. We
      hypothesize that excess fishing of females caused the declining biomass trend of
      the brown swimming crab in Sonora, and concluded on the convenience of
      implementing harvest refugia inside coastal wetlands to protect females during
      the spawning season.

PMID- 29462543
TI  - [Micromorphology of pejibaye leaflets Bactris gasipaes (Arecaceae) var. diamonds
      10].
AB  - Bactris gasipaes is widely cultivated for the consumption of palm hearts and
      fruits. The present work describes the micro morphological characteristics of
      leaflets from adult plants of B. gasipaes, thornless variety Diamantes-10,
      collected in the Diamantes Experimental Station in Guapiles, Costa Rica. We
      collected 25 leaflets and analyses were performed with a combination of
      microscopy techniques: light microscopy, scanning electron microscopy and
      transmission electron microscopy to study their structure. Our results showed
      that leaflets have abundant epicuticular wax on adaxial and abaxial surfaces.
      Analyses from the epidermis indicated that it is composed of isodiametric cells,
      and it is also evident that hypodermis cells have rectangular shape and are
      larger than the other epidermal cells. We observed stomata on both surfaces, but
      they were more abundant in the abaxial surface. On the other hand, the epidermis
      showed the presence of trichomes with three different morphologies. In the
      parenchyma, cells are large and not well defined, and we observed the presence of
      astroesclereids, and compact groups of fiber bundles between parenchyma cells.
      The central vein has several vascular bundles, arranged in a continuous manner,
      and they are surrounded by sclerotic tissue; some of these fibers presented live
      protoplasts. All minor veins showed the same anatomy as the central vein. In
      these veins, the vessel elements of protoxylem and metaxylem showed scalariform
      ornaments on their walls. Phloem is located towards the adaxial surface of the
      vein and we observed sieve and companion cells surrounded by fibers and
      parenchyma cells. The companion cells presented branched plasmodesmata attached
      to a sieve element, and in these elements we found protein bodies called P
      protein. The main anatomical difference in the leaflets of the var. Diamantes-10,
      compared to the other varieties of B. gasipaes K, is the lack of thorns; the
      other morphological features seem to be conserved.

PMID- 29462544
TI  - Population dynamics and reproductive biology of Barilius bendelisis (Cyprinidae:
      Cypriniformes) from river Gaula of Central Indian Himalaya.
AB  - The Indian hill trout cyprinid, Barilius bendelisis is a member of family
      Cyprinidae that dwells in shallow, cold, and clear water. In this study, growth
      parameters and reproductive biology of Indian hill trout, Barilius bendelisis
      from river Gaula, Central Himalaya region, India, were studied. The length
      frequency data were grouped sex wise and were analyzed to determine the growth
      and mortality parameters using the computer software programme, FAO-ICLARM Stock
      Assessment Tool (FISAT II). Altogether, 501 individuals were collected from river
      Gaula (November 2013-October 2014) and were preserved in formalin for further
      analysis. The results showed that the female outnumbered the male population. The
      minimum GSI of females was observed in the month of October (4.93 +/- 0.26) and
      for males in the month of June and July (0.093 +/- 0.12), whereas, the maximum
      value was in the month of April for both females (13.47 +/- 0.52) and males (1.21
      +/- 0.12). Fluctuation in GSI values had a bimodal pattern showing two peaks
      during March-May and August-September in both the sexes, indicating the common
      spawning period of fish. The slope of regression showed the negative allometric
      growth for both males and females (b= 2.65 for male and b= 2.5 for female). A
      significant relationship between length and weight was observed in the present
      study (p < 0.05). The ELEFAN-I estimated Linfinity and K of the von Bertalanffy
      growth factor for males (17.33 cm and 0.310 per year), females (17.33 cm and 0.3
      per year) and pooled sexes (17.33 cm and 0.240 per year). The results indicated
      that Barilius bendelisis is a small sized fish having negative allometric growth
      that spawns twice a year. Thus, the present study on biological traits represents
      the baseline information for effective production, conservation and restoration
      planning.

PMID- 29462545
TI  - [Capture and selectivity of zooplankton by Utricularia foliosa (Lentibulariaceae)
      in the Cienaga de Paredes, Santander, Colombia].
AB  - Utricularia is a genus of carnivorous plants that capture a wide range of aquatic
      organisms. Most of these plants grow in environments with nutrients deficiency
      and have the ability to change the conditions of their microenvironment. The aim
      of this research was to study the selectivity in the zooplankton capture by
      Utricularia foliosa in the Cienaga de Paredes. Our study was undertaken between
      February and November, 2014. We tried to determine if there is selection in the
      plant's food resources by the Czekanowski's index, and the selection degree by
      the Savage and Ivlev's indexes. Additionally, we studied the possible
      relationship between the patterns of zooplankton capture and selection, with
      physicochemical variables in the swamp. The Czekanowski's index showed a food
      selection in plant resources throughout the flood pulse, with values between 0.28
      and 0.41. We also found a significant positive selection with Savage's index for
      Lecane sp., Alona sp., Ceriodaphnia sp., and Bosmina sp. (p < 0.05); similar
      results were obtained with Ivlev's index. The intensity in the selection of each
      captured genus varied significantly between hydrological periods and between high
      and low water levels in the swamp. It was possible to identify some changes in
      the ammonia and nitrate concentration and some variability in the electric
      conductivity of the swamp, which influenced the captures made by U. foliosa. This
      is the first paper that allows an approach to understand the selection of food
      resources for the species, using a selectivity index, and one of the few for the
      genus.

PMID- 29462547
TI  - Brachiopods, sipunculans, enteropneusts and metals from two estuarine tidal
      flats, Pacific, Costa Rica.
AB  - Reports on the abundances and on metal concentrations in intertidal estuarine
      invertebrates from theEastern Tropical Pacific are rare. Thus, the objectives of
      this report are to make accessible data on the abundances(1984-1987, 49 dates;
      2013, 12 dates) of sipunculans, brachiopods and hemichordates from a sand-mud
      flat; and ontrace metals (1996, 2000) and abundances (2015, 3 dates) of
      sipunculans and brachiopods at a sand flat in the Gulfof Nicoya estuary (10o N
      85o W). Cores (17.7 cm2) were collected at the sand-mud flat, and quadrats (0.2
      m2) atthe sand flat. The flats contrasted in their sand (65 % vs 90 %) and
      silt+clay (31.5 % vs 5.6 %) contents. At thesand-mud flat (1984-87: 1.83 m2) the
      sipunculans were represented by 13 individuals, the brachiopods by 129 andthe
      acorn worms by 185, with estimated maximum densities of: 5.7, 29, and 40 ind./m2,
      respectively. Trace metal(Fe, Mn, Ni, Cr, Cd, Zn, and Pb) analysis (Atomic
      Absorption Spectrometry) were conducted in specimens ofSipunculus nudus
      (Sipuncula) and Glottidia audebarti (Brachiopoda). Maximum mean concentrations in
      S. nuduswere: For non-depurated worms, Fe (16.0 mg/g dw) > Mn (165 MUg/g dw) > Zn
      (81 MUg/g dw) > Cu (26 MUg/g dw)> Cr (11 MUg/g dw) > Ni (10.4 MUg/g dw) > Pb (9.3
      MUg/g dw) > Cd (1.2 MUg/g dw). For 72 hour depurated worms:Fe (5.0 mg/g dw) > Mn
      (61 MUg/g dw) > Zn (39 MUg/g dw) > Cu (24 MUg/g dw) > Ni (8.4 MUg/g dw) > Pb (2.7
      MUg/gdw) > Cd (0.62 MUg/g dw). For G. audebarti: Fe (1.6 mg/g dw-soft parts) > Zn
      (123.5 MUg/g dw-soft parts) > Cu(31.4 MUg/g dw-pedicles) > Pb (21.0 MUg/g dw
      shells) > Cd (5.2 MUg/g dw-soft parts) > Cr (4.7 MUg/g dw-shells). Forsediments;
      Fe (46 mg/g dw) > Mn (41.3 MUg/g dw) > Zn (63 MUg/g dw) > Cu (36.2 MUg/g dw) > Cr
      (31.5 MUg/g dw)> Pb (21.1 MUg/g dw) > Ni (16.1 MUg/g dw) > Cd (1.1 MUg/g dw).
      These concentrations were expected for a nonindustrializedestuary. At the sand
      flat (Area sampled: 10.6 m2 ) 76 individuals of G. audebarti, 112 of G.
      albida,and 366 of S. nudus were collected in 2015, with estimated maximum
      densities of: 7.1, 10.5, and 31 ind./m2,respectively. Densities of G. audebarti
      and G. albida were relatively low, while those of S. nudus were relativelyhigh
      when compared with other reports. The shell lenght of G. audebarti ranged from
      9.0 mm to 38.0 mm and from6.0 mm to 29.0 mm for G. albida. These ranges were
      within those found for these lingulides elsewhere. The meanlength of S. nudus was
      41 mm and the maximum weight was 1.6 g, which are small. No brachiopods were
      found atthe sand-mud flat in 2013, nor enteropneusts at the sand flat in 2015. G.
      audebarti had a relatively stable presence,while G. albida almost vanished from
      the samples at the end of 2015. The spatial distributions of the three
      invertebrateswere found aggregated at both intertidal flats. Strong ENSO warming
      events during 1983 and 2015, and redtides in 1985 may have influenced the
      abundances.

PMID- 29462548
TI  - Understory bat roosts, availability and occupation patterns in a Neotropical
      rainforest of Costa Rica.
AB  - The strong link between bats and their roosts is widely recognized as being
      particularly significant. Despite this, roosting ecology of bats is poorly
      understood and much of the basic information is still unknown. In this study, we
      investigated the availability and occupation patterns of four roost types (trees,
      caves, termite nests and tents) used by bats at Tirimbina Biological Reserve
      (TBR), Costa Rica. To accomplish our aim, we systematically surveyed both sides
      of established trails and transects, looking for understory roosts. Potential
      roosts were examined for bat presence in order to establish occupation. Roost
      availability and density were estimated using traveled distances (km) and
      inspected area (10 m for trees/caves and 15 m for tents/termite nests) of each
      trail or transect sampled. For the tent roosts, data on taxonomic information of
      plant modified, type of architecture, condition and construction achievement were
      also recorded. The area surveyed represented 45.4 % of the total area of the TBR
      (345 ha). Tents were the most common roost (56.6 % of all roosts, N = 223),
      followed by trees (24.4 %, N = 96), termite nests (18.8 %, N = 74) and caves (0.2
      %, N = 1). We detected only 27 roosts occupied by bats (6.8 % of all roosts, 0.17
      occupied roosts/ha). Caves showed the highest occupation rate (100 %, N = 1),
      followed by trees (17.7 %, N = 17), tents (3.6 %, N = 8) and termite nests (1.3
      %, N = 1). We found the roosts for 10 species, representing 33.9 % of the bat
      fauna documented at the reserve (62 species). Density of roosts per bat species
      varied between 0.017-0.138 roosts/ha. Phyllostomidae was the best-represented
      family with Micronycteris microtis representing the most common species
      encountered. Four distinct tent architectures were documented. Bifid architecture
      was the most common (133 tents), followed by Conical (47 tents), Apical (27
      tents) and Inverted Boat (16 tents). Most of the tents found were healthy (76.7
      %, N = 171) and totally constructed (88.8 %, N = 198). Our study demonstrated
      that occupied bat roosts are difficult to find in the forest. When compared to
      the roost availability, the low occupation rates suggested that, at least in our
      study area, roosts might not be a limiting resource. Nevertheless, to confirm
      this hypothesis, information about fidelity and selection process of the species
      is fundamental for understanding to what extent these roosts meet the
      requirements to be inhabited or modified. Worldwide conservation efforts on bats
      should focus on understanding roosting ecology, especially due to anthropogenic
      pressures that are continuously reducing the availability of roosts, which
      undoubtedly contributes to the risk of extinction for specialized and sensitive
      species.

PMID- 29462546
TI  - Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension.
AB  - The renin-angiotensin system (RAS) is an important regulator of cirrhosis and
      portal hypertension. As hepatic fibrosis progresses, levels of the RAS components
      angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), and Ang II
      type 1 receptor (AT1R) are increased. The primary effector Ang II regulates
      vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and
      inflammation in various diseases, including liver cirrhosis, through the ACE/Ang
      II/AT1R axis in the classical RAS. The ACE2/Ang-(1-7)/Mas receptor and ACE2/Ang
      (1-9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth,
      proapoptotic, and anti-inflammatory effects; thus, countering the effects of the
      classical RAS axis to reduce hepatic fibrogenesis and portal hypertension.
      Patients with portal hypertension have been treated with RAS antagonists such as
      ACE inhibitors, Ang receptor blockers, and aldosterone antagonists, with very
      promising hemodynamic results. In this review, we examine the RAS, its roles in
      hepatic fibrosis and portal hypertension, and current therapeutic approaches
      based on the use of RAS antagonists in patients with portal hypertension.

PMID- 29462549
TI  - [Physiological condition of an Arca zebra (Bivalvia: Arcidae) population from
      Chacopata, Sucre, Venezuela].
AB  - Condition indices reflect the performance of an organism in their environment, as
      well as theirsomatic condition, nutritional value, commercial importance, the
      ecological role and fattening periods. In thisstudy, different physiological
      indices were evaluated in order to know the Arca zebra population status, and
      tosuggest operation and sustainability strategies for this resource use and
      consumption. A total of 240 samples (82males and 158 females) were collected
      between July 2010 and July 2011, from the Chacopata bank site. Bivalvebiometric
      measurements were made monthly and considered: total shell length, height and
      width; besides, softtissues were dehydrated to obtain total dry mass. Different
      condition indices were analyzed based on the bodymass, or on the combination of
      mass and shell length: gonadal index, muscle index, meat yield, the fresh mass
      ofsoft tissue in relation to the total length, and dry mass of soft tissue
      relative to the total length. We found the modelwith positive allometric growth
      between the length-total dry mass. The gonadal weight exerted a marked
      influenceon the condition index, gonadosomatic index and meat yield. Increases in
      soft tissue mass were proportionalto the dimensions of the shell. The index
      contrasts fresh mass of soft tissue in relation to the total length, as a
      toolthat would allow fishers to estimate the population dynamics of A. zebra, and
      to practice a sustainable fisheryover time, while keeping the extraction canons.

PMID- 29462551
TI  - Copper-Coupled Electron Transfer in Colloidal Plasmonic Copper-Sulfide
      Nanocrystals Probed by in Situ Spectroelectrochemistry.
AB  - Copper-sulfide nanocrystals can accommodate considerable densities of delocalized
      valence-band holes, introducing localized surface plasmon resonances (LSPRs)
      attractive for infrared plasmonic applications. Chemical control over nanocrystal
      shape, composition, and charge-carrier densities further broadens their scope of
      potential properties and applications. Although a great deal of control over
      LSPRs in these materials has been demonstrated, structural complexities have
      inhibited detailed descriptions of the microscopic chemical processes that
      transform them from nearly intrinsic to degenerately doped semiconductors. A
      comprehensive understanding of these transformations will facilitate use of these
      materials in emerging technologies. Here, we apply spectroelectrochemical
      potentiometry as a quantitative in situ probe of copper-sulfide nanocrystal Fermi
      level energies ( EF) during redox reactions that switch their LSPR bands on and
      off. We demonstrate spectroscopically indistinguishable LSPR bands in low
      chalcocite copper-sulfide nanocrystals with and without lattice cation vacancies
      and show that cation vacancies are much more effective than surface anions at
      stabilizing excess free carriers. The appearance of the LSPR band, the shift in
      EF, and the change in crystal structure upon nanocrystal oxidation are all fully
      reversible upon addition of outer-sphere reductants. These measurements further
      allow quantitative comparison of the coupled and stepwise oxidation/cation
      vacancy-formation reactions associated with LSPRs in copper-sulfide nanocrystals,
      highlighting fundamental thermodynamic considerations relevant to technologies
      that rely on reversible or low-driving-force plasmon generation in semiconductor
      nanostructures.

PMID- 29462552
TI  - Revealing Abrupt and Spontaneous Ruptures of Protein Native Structure under
      picoNewton Compressive Force Manipulation.
AB  - Manipulating protein conformations for exploring protein structure-function
      relationship has shown great promise. Although protein conformational changes
      under pulling force manipulation have been extensively studied, protein
      conformation changes under a compressive force have not been explored
      quantitatively. The latter is even more biologically significant and relevant in
      revealing protein functions in living cells associated with protein crowdedness,
      distribution fluctuations, and cell osmotic stress. Here we report our
      experimental observations on abrupt ruptures of protein native structures under
      compressive force, demonstrated and studied by single-molecule AFM-FRET
      spectroscopic nanoscopy. Our results show that the protein ruptures are abrupt
      and spontaneous events occurred when the compressive force reaches a threshold of
      12-75 pN, a force amplitude accessible from thermal fluctuations in a living
      cell. The abrupt ruptures are sensitive to local environment, likely a general
      and important pathway of protein unfolding in living cells.

PMID- 29462550
TI  - Three-dimensional Architecture Enabled by Strained Two-dimensional Material
      Heterojunction.
AB  - Engineering the structure of materials endows them with novel physical properties
      across a wide range of length scales. With high in-plane stiffness and strength,
      but low flexural rigidity, two-dimensional (2D) materials are excellent building
      blocks for nanostructure engineering. They can be easily bent and folded to build
      three-dimensional (3D) architectures. Taking advantage of the large lattice
      mismatch between the constituents, we demonstrate a 3D heterogeneous architecture
      combining a basal Bi2Se3 nanoplate and wavelike Bi2Te3 edges buckling up and down
      forming periodic ripples. Unlike 2D heterostructures directly grown on
      substrates, the solution-based synthesis allows the heterostructures to be free
      from substrate influence during the formation process. The balance between
      bending and in-plane strain energies gives rise to controllable rippling of the
      material. Our experimental results show clear evidence that the wavelengths and
      amplitudes of the ripples are dependent on both the widths and thicknesses of the
      rippled material, matching well with continuum mechanics analysis. The rippled
      Bi2Se3/Bi2Te3 heterojunction broadens the horizon for the application of 2D
      materials heterojunction and the design and fabrication of 3D architectures based
      on them, which could provide a platform to enable nanoscale structure generation
      and associated photonic/electronic properties manipulation for optoelectronic and
      electromechanic applications.

PMID- 29462553
TI  - Light-Activated Core-Shell Nanoparticles for Spatiotemporally Specific Treatment
      of Metastatic Triple-Negative Breast Cancer.
AB  - Triple-negative breast cancer (TNBC) tumors are heterogeneous, with mesenchymal
      like cells at their core and fast proliferating cells on the periphery. It is
      desirable and beneficial to treat TNBC cells of different phenotypes with the
      most appropriate drugs. Here, we report a 78 nm, chlorin e6-, docetaxel-, and
      anti-Twist siRNA-containing polymeric nanoparticle (CDTN) with spatiotemporally
      specific activity when irradiated by light. Under conditions mimicking
      superficial tumor tissue with sufficient light input, TNBC cells are mainly
      killed by the photodynamic therapy (PDT) function of CDTNs. In contrast, under
      conditions mimicking deep tumor tissue with weak light input, PDT potentiates
      chemotherapy (CT) and gene therapy (GT) by facilitating the endolysosomal escape
      of CDTNs. Compared with free drugs, CDTNs improve the intratumoral exposure of
      docetaxel and anti-Twist siRNA by 2.5- and 2-fold, respectively. When combined
      with laser irradiation applied at the time of maximal intratumoral accumulation,
      the CDTNs significantly inhibit the growth of primary tumors and their lung
      metastasis (both >80%) by killing the peripheral cells, mainly through PDT and
      prohibiting the growth and metastasis of deep cells through PDT as enhanced CT
      and GT. On the contrary, dual-modality nanomedicine lacking CT, GT, or PDT showed
      fast primary tumor growth, poor metastasis control, or both, respectively. This
      study reveals the spatiotemporally specific mechanism of CDTNs in treating
      metastatic TNBC and highlights the importance of combined therapy in treating
      TNBC.

PMID- 29462555
TI  - When Al-Doped Cobalt Sulfide Nanosheets Meet Nickel Nanotube Arrays: A Highly
      Efficient and Stable Cathode for Asymmetric Supercapacitors.
AB  - Although cobalt sulfide is a promising electrode material for supercapacitors,
      its wide application is limited by relative poor electrochemical performance, low
      electrical conductivity, and inefficient nanostructure. Here, we demonstrated
      that the electrochemical activity of cobalt sulfide could be significantly
      improved by Al doping. We designed and fabricated hierarchical core-branch Al
      doped cobalt sulfide nanosheets anchored on Ni nanotube arrays combined with
      carbon cloth (denoted as CC/H-Ni@Al-Co-S) as an excellent self-standing cathode
      for asymmetric supercapacitors (ASCs). The combination of structural and
      compositional advantages endows the CC/H-Ni@Al-Co-S electrode with superior
      electrochemical performance with high specific capacitance (1830 F g-1/2434 F g-1
      at 5 mV s-1/1 A g-1) and excellent rate capability (57.2%/72.3% retention at 1000
      mV s-1/100 A g-1). The corresponding all-solid-state ASCs with CC/H-Ni@Al-Co-S
      and multilayer graphene/CNT film as cathode and anode, respectively, achieve a
      high energy density up to 65.7 W h kg-1 as well as superb cycling stability
      (90.6% retention after 10 000 cycles). Moreover, the ASCs also exhibit good
      flexibility and stability under different bending conditions. This work provides
      a general, effective route to prepare high-performance electrode materials for
      flexible all-solid-state energy storage devices.

PMID- 29462556
TI  - WO3/Conducting Polymer Heterojunction Photoanodes for Efficient and Stable
      Photoelectrochemical Water Splitting.
AB  - An efficient and stable heterojunction photoanode for solar water oxidation was
      fabricated by hybridization of WO3 and conducting polymers (CPs).
      Organic/inorganic hybrid photoanodes were readily prepared by the
      electropolymerization of various CPs and the codeposition of tetraruthenium
      polyoxometalate (Ru4POM) water-oxidation catalysts (WOCs) on the surface of WO3.
      The deposition of CPs, especially polypyrrole (PPy) doped with Ru4POM
      (PPy:Ru4POM), resulted in a remarkably improved photoelectrochemical performance
      by the formation of a WO3/PPy p-n heterojunction and the incorporation of
      efficient Ru4POM WOCs. In addition, there was also a significant improvement in
      the photostability of the WO3-based photoanode after the deposition of the
      PPy:Ru4POM layer due to the suppression of the formation of hydrogen peroxide,
      which was responsible for corrosion. This study provides insight into the design
      and fabrication of novel photosynthetic and photocatalytic systems with excellent
      performance and stability through the hybridization of organic and inorganic
      materials.

PMID- 29462557
TI  - Honeydew Honeys: A Review on the Characterization and Authentication of Botanical
      and Geographical Origins.
AB  - The commercial interest in honeydew honeys (from the secretions of plants or the
      excretions of plant-sucking insects found on plants) is increasing because of
      their higher therapeutic properties compared with those of most blossom honeys
      (from nectar). However, honeydew honeys have been less studied than blossom
      honeys. In this work, studies carried out to characterize and authenticate
      honeydew honeys by their botanical and geographical origins have been reviewed.
      The identification of honey origins has been approached by two ways: by the
      analysis of chemical markers and by the development of analytical methodologies
      combined with multivariate analyses. Some compounds have been suggested as
      specific botanical markers of several honeydew honeys, such as quercitol and
      trans-oak lactone for oak honey, 2-aminoacetophenone and propylanisol for holm
      oak honey, and 1-chloro-octane and tridecane for pine honey. The presence of 3
      carene and an unidentified compound in samples was proposed as a way discriminate
      between Greek and Turkish pine honeys. Chemometric analyses have been applied on
      chemical compositions and on physicochemical, microscopic, and spectral
      parameters and have proved to be valuable methods for authenticating honeydew
      honeys. Analytical methods based on spectral information are suitable for the
      routine control of honeydew-honey origins because they are fast and require easy
      sample preparations.

PMID- 29462554
TI  - Big Potential from Small Agents: Nanoparticles for Imaging-Based Companion
      Diagnostics.
AB  - The importance of medical imaging in the diagnosis and monitoring of cancer
      cannot be overstated. As personalized cancer treatments are gaining popularity, a
      need for more advanced imaging techniques has grown significantly. Nanoparticles
      are uniquely suited to fill this void, not only as imaging contrast agents but
      also as companion diagnostics. This review provides an overview of many ways
      nanoparticle imaging agents have contributed to cancer imaging, both
      preclinically and in the clinic, as well as charting future directions in
      companion diagnostics. We conclude that, while nanoparticle-based imaging agents
      are not without considerable scientific and developmental challenges, they enable
      enhanced imaging in nearly every modality, hold potential as in vivo companion
      diagnostics, and offer precise cancer treatment and maximize intervention
      efficacy.

PMID- 29462558
TI  - Molecular Imaging of Mesothelin-Expressing Ovarian Cancer with a Human and Mouse
      Cross-Reactive Nanobody.
AB  - Mesothelin is an epithelial marker highly expressed at the cell surface of cancer
      cells from diverse origins, including ovarian and pancreatic adenocarcinomas and
      mesotheliomas. Previously, we identified and characterized an antimesothelin
      nanobody (NbG3a) for in vitro diagnostic applications. The main goal of this
      research was to establish the potential of NbG3a as a molecular imaging agent.
      Site-specific biotinylated NbG3a (bNbG3a) was bound to streptavidin-conjugated
      reagents for in vitro and in vivo assays. Initially, we performed microscale
      thermophoresis to determine the binding affinity between bNbG3a and human ( Kd =
      46 +/- 8 nM) or mouse ( Kd = 4.8 +/- 0.4 nM) mesothelin protein. The human and
      mouse cross-reactivity was confirmed by in vivo optical imaging using bNbG3a
      bound to fluorescent streptavidin. We also localized the binding site of nNbG3a
      on human mesothelin using overlapping peptide scan. NbG3a recognized an epitope
      within residues 21-65 of the mature membrane bound form of human mesothelin,
      which is part of the N-terminal region of mesothelin that is important for
      interactions between mesothelin on peritoneal cells and CA125 on tumor cells.
      Next, the bNbG3a in vivo half-life after intravenous injection in healthy mice
      was estimated by ELISA assay to be 5.3 +/- 1.3 min. In tumor-bearing animals,
      fluorescent bNbG3a accumulated in a subcutaneous ovarian xenograft (A1847) and in
      two syngeneic, orthotopic ovarian tumors (intraovary and intraperitoneal ID8)
      within an hour of intravenous injection that peaked by 4 h and persisted up to 48
      h. MRI analysis of bNbG3a-targeted streptavidin-labeled iron oxides showed that
      the MRI signal intensity decreased 1 h after injection for a subcutaneous
      xenograft model of ovarian cancer for bNbG3a-labeled iron oxides compared to
      unlabeled iron oxides. The signal intensity differences continued up to the final
      time point at 24 h post injection. Finally, in vivo immunofluorescence 24 or 48 h
      after bNbG3a intravenous injection showed bNbG3a diffuse distribution of both
      xenograft and syngeneic ovarian tumors, with local areas of high concentration
      throughout A1847 human tumor. The data support the use of NbG3a for continued
      preclinical development and translation to human applications for cancers that
      overexpress mesothelin.

PMID- 29462559
TI  - Conversion of "Waste Plastic" into Photocatalytic Nanofoams for Environmental
      Remediation.
AB  - Plastic debris is a major environmental concern, and to find effective ways to
      reuse polystyrene (PS) presents major challenges. Here, it is demonstrated that
      polystyrene foams impregnated with SnO2 are easily generated from plastic debris
      and can be applied to photocatalytic degradation of dyes. SnO2 nanoparticles were
      synthesized by a polymeric precursor method, yielding specific surface areas of
      15 m2/g after heat treatment to 700  degrees C. Crystallinity, size, and shape of
      the SnO2 particles were assessed by X-ray diffraction (XRD) and transmission
      electron microscopy (TEM), demonstrating the preparation of crystalline spherical
      nanoparticles with sizes around 20 nm. When incorporated into PS foams, which
      were generated using a thermally induced phase separation (TIPS) process, the
      specific surface area increased to 48 m2/g. These PS/SnO2 nanofoams showed very
      good efficiency for photodegradation of rhodamine B, under UV irradiation,
      achieving up to 98.2% removal. In addition the PS/SnO2 nanofoams are shown to
      retain photocatalytic activity for up to five reuse cycles.

PMID- 29462560
TI  - Density Functional Theory and the Basis Set Truncation Problem with Correlation
      Consistent Basis Sets: Elephant in the Room or Mouse in the Closet?
AB  - Two recent papers in this journal called into question the suitability of the
      correlation consistent basis sets for density functional theory (DFT)
      calculations, because the sets were designed for correlated methods such as
      configuration interaction, perturbation theory, and coupled cluster theory. These
      papers focused on the ability of the correlation consistent and other basis sets
      to reproduce total energies, atomization energies, and dipole moments obtained
      from "quasi-exact" multiwavelet results. Undesirably large errors were observed
      for the correlation consistent basis sets. One of the papers argued that basis
      sets specifically optimized for DFT methods were "essential" for obtaining high
      accuracy. In this work we re-examined the performance of the correlation
      consistent basis sets by resolving problems with the previous calculations and by
      making more appropriate basis set choices for the alkali and alkaline-earth
      metals and second-row elements. When this is done, the statistical errors with
      respect to the benchmark values and with respect to DFT optimized basis sets are
      greatly reduced, especially in light of the relatively large intrinsic error of
      the underlying DFT method. When judged with respect to high-quality Feller
      Peterson-Dixon coupled cluster theory atomization energies, the PBE0 DFT method
      used in the previous studies exhibits a mean absolute deviation more than a
      factor of 50 larger than the quintuple zeta basis set truncation error.

PMID- 29462561
TI  - Impact of Edge Groups on the Hydration and Aggregation Properties of Graphene
      Oxide.
AB  - Molecular dynamics simulations were used to describe and quantify the role of
      edge groups on the hydrating properties of graphene oxide (GO). For this, six
      different oxygen concentrations were investigated, and in four of them, carboxyl
      groups were present. Structural analysis indicates a greater probability for the
      water solvation around the GO edges in detriment of the region of its basal
      plane, while hydrogen bonding analyses indicates that edge groups are very
      expressive, participating in about 60% of the total number of bonds. The impact
      of this bond network formed by edge groups is rationalized in energetic and
      thermodynamic terms. The resulting hydrophilicity observed, as expected, is of
      electrostatic origin and has a larger contribution from the edge groups that
      varies from 22 to 57% depending on the concentration. Hydration free energy and
      potential of mean force calculations support these findings. It was observed that
      the edge groups contribute up to 51% of the total hydration-free energy and that
      the PMF indicates the tendency for spontaneous aggregation at all investigated
      concentrations, being lower the higher the concentration of oxygen.

PMID- 29462562
TI  - Exosome-Mediated Ultra-Effective Direct Conversion of Human Fibroblasts into
      Neural Progenitor-like Cells.
AB  - Exosomes, naturally secreted nanoparticles, have been introduced as vehicles for
      horizontal transfer of genetic material. We induced autologous exosomes
      containing a cocktail of reprogramming factors ("reprosomes") to convert
      fibroblasts into neural progenitor cells (NPCs). The fibroblasts were treated
      with ultrasound and subsequently cultured in neural stem cell medium for 1 day to
      induce the release of reprosomes composed of reprogramming factors associated
      with chromatin remodeling and neural lineage-specific factors. After being
      treated with reprosomes, fibroblasts were converted into NPCs (rNPCs) with great
      efficiency via activation of chromatin remodeling, so quickly that only 5 days
      were required for the formation of 1500 spheroids showing an NPC-like phenotype.
      The rNPCs maintained self-renewal and proliferative properties for several weeks
      and successfully differentiated into neurons, astrocytes, and oligodendrocytes in
      vitro and in vivo. Reprosome-mediated cellular reprogramming is simple, safe, and
      efficient to produce autologous stem cells for clinical application.

PMID- 29462563
TI  - Experimental Determination of Drug Diffusion Coefficients in Unstirred Aqueous
      Environments by Temporally Resolved Concentration Measurements.
AB  - The diffusion coefficient (also known as diffusivity) of an active pharmaceutical
      ingredient (API) is a fundamental physicochemical parameter that affects passive
      diffusion through biological barriers and, as a consequence, bioavailability and
      biodistribution. However, this parameter is often neglected, and it is quite
      difficult to find diffusion coefficients of small molecules of pharmaceutical
      relevance in the literature. The available methods to measure diffusion
      coefficients of drugs all suffer from limitations that range from poor
      sensitivity to high selectivity of the measurements or the need for dedicated
      instrumentation. In this work, a simple but reliable method based on time
      resolved concentration measurements by UV-visible spectroscopy in an unstirred
      aqueous environment was developed. This method is based on spectroscopic
      measurement of the variation of the local concentration of a substance during
      spontaneous migration of molecules, followed by standard mathematical treatment
      of the data in order to solve Fick's law of diffusion. This method is extremely
      sensitive and results in highly reproducible data. The technique was also
      employed to verify the influence of the environmental characteristics (i.e.,
      ionic strength and presence of complexing agents) on the diffusivity. The method
      can be employed in any research laboratory equipped with a standard UV-visible
      spectrophotometer and could become a useful and straightforward tool in order to
      characterize diffusion coefficients in physiological conditions and help to
      better understand the drug permeability process.

PMID- 29462564
TI  - Practice Patterns of Referring Physicians in Management of the Dysphonic Patient.
AB  - Objective Dysphonia is commonly encountered by primary care physicians and
      general otolaryngologists. We examine practice patterns of referring physicians
      to a tertiary voice clinic, including adherence to evidence-based guidelines.
      Study Design Retrospective case series with chart review. Setting Academic
      tertiary care hospital. Subjects and Methods In total, 821 charts of patients
      with voice complaints seen at a tertiary voice clinic between January 2011 and
      June 2016 were reviewed. Included charts (n = 755) were reviewed for type of
      referring provider, prior diagnoses, and treatments employed by referring
      physicians. Additional information regarding findings at the time of
      laryngoscopy/stroboscopy and diagnoses provided by a laryngologist were also
      obtained. Statistical analysis was performed to determine significant
      relationships between variables of interest. Results A total of 244 patients
      (32.2%) received a diagnosis prior to evaluation in the voice clinic, most
      commonly laryngopharyngeal reflux disease (n = 134). Prior medical treatment was
      attempted in 221 (29.3%) patients, typically antireflux medications (n = 141). Of
      the patients treated with proton pump inhibitors by referring physicians, 65.1%
      lacked symptoms of gastroesophageal reflux disease. Patients with prior treatment
      had a median duration of symptoms 6 weeks longer than those without prior
      treatment ( P = .04). Among previously diagnosed patients, 199 (81.6%) of
      diagnoses changed after evaluation in the voice clinic. Conclusion Referring
      physicians frequently treat dysphonic patients empirically, often with antireflux
      medications. Subspecialist evaluation results in changes in diagnosis in many
      patients. Empiric treatment can delay referral and appropriate treatment.

PMID- 29462565
TI  - Pycnogenol protects against diet-induced hepatic steatosis in apolipoprotein-E
      deficient mice.
AB  - PycnogenolR (PYC), a combination of active flavonoids derived from French
      maritime pine bark, is a natural antioxidant that has various pharmacological
      activities. Here, we investigated the beneficial effect of PYC on diet-induced
      hepatic steatosis. Apolipoprotein E (ApoE)-deficient male mice were administered
      PYC at oral doses of 30 or 100 mg.kg-1.day-1 for 2 wk in advance and were then
      fed a high-cholesterol and -fat diet (HCD) for 8 wk. Biochemical,
      immunohistochemical, and gene expression analyses were conducted to explore the
      effect of PYC on lipid metabolism in ApoE-deficient mice on a HCD. Short-term
      treatment with HCD in ApoE-deficient mice induced hepatic injuries, such as lipid
      metabolism disorder and hepatic histopathological changes. We found that PYC
      reduced body weight and the increase of serum lipids that had been caused by HCD.
      Supplementation of PYC significantly reduced lipid deposition in the liver, as
      shown by the lowered hepatic lipid content and histopathological lesions. We
      subsequently detected genes related to lipid metabolism and inflammatory
      cytokines. The study showed that PYC markedly suppressed the expression of genes
      related to hepatic lipogenesis, fatty acid uptake, and lipid storage while
      increasing the lipolytic gene, which thus reduced hepatic lipid content.
      Furthermore, PYC mainly reduced the expression of inflammatory cytokines and the
      infiltration of inflammatory cells, which were resistant to the development of
      hepatic steatosis. These results demonstrate that PYC protects against the
      occurrence and development of hepatic steatosis and may provide a new
      prophylactic approach for nonalcoholic fatty liver disease (NAFLD).

PMID- 29462567
TI  - World Health Assembly Resolution 69.9 Calls for an End to Unethical Marketing of
      "Baby Foods".

PMID- 29462568
TI  - Institutions, Incorporation, and Inequality: The Case of Minority Health
      Inequalities in Europe.
AB  - Scholars interested in the relationship between social context and health have
      recently turned attention further "upstream" to understand how political, social,
      and economic institutions shape the distribution of life chances across contexts.
      We compare minority health inequalities across 22 European countries ( N =
      199,981) to investigate how two such arrangements-welfare state effort and
      immigrant incorporation policies-influence the distribution of health and health
      inequalities. We examine two measures of health from seven waves of the European
      Social Survey. Results from a series of multilevel mixed-effects models show that
      minority health inequalities vary across contexts and persist after accounting
      for socioeconomic differences. Cross-level interaction results show that welfare
      state effort is associated with better health for all groups but is unrelated to
      levels of inequality between groups. In contrast, policies aimed at protecting
      minorities from discrimination correlate with smaller relative health
      inequalities.

PMID- 29462566
TI  - Nonalcoholic fatty liver disease and gastric bypass surgery regulate serum and
      hepatic levels of pyruvate kinase isoenzyme M2.
AB  - Treatment of nonalcoholic fatty liver disease (NAFLD) focuses on the underlying
      metabolic syndrome, and Roux-en-Y gastric bypass surgery (RYGB) remains one of
      the most effective options. In rodents and human patients, RYGB induces an
      increase in the gene and protein expression levels of the M2 isoenzyme of
      pyruvate kinase (PKM2) in the jejunum. Since PKM2 can be secreted in the
      circulation, our hypothesis was that the circulating levels of PKM2 increase
      after RYGB. Our data, however, revealed an unexpected finding and a potential new
      role of PKM2 for the natural history of metabolic syndrome and NAFLD. Contrary to
      our initial hypothesis, RYGB-treated patients had decreased PKM2 blood levels
      compared with a well-matched group of patients with severe obesity before RYGB.
      Interestingly, PKM2 serum concentration correlated with body mass index before
      but not after the surgery. This prompted us to evaluate other potential
      mechanisms and sites of PKM2 regulation by the metabolic syndrome and RYGB. We
      found that in patients with NAFLD and nonalcoholic steatohepatitis (NASH), the
      liver had increased PKM2 expression levels, and the enzyme appears to be
      specifically localized in Kupffer cells. The study of murine models of metabolic
      syndrome and NASH replicated this pattern of expression, further suggesting a
      metabolic link between hepatic PKM2 and NAFLD. Therefore, we conclude that PKM2
      serum and hepatic levels increase in both metabolic syndrome and NAFLD and
      decrease after RYGB. Thus, PKM2 may represent a new target for monitoring and
      treatment of NAFLD.

PMID- 29462569
TI  - Linguistic Integration and Immigrant Health: The Longitudinal Effects of
      Interethnic Social Capital.
AB  - The literature on immigrant health has by and large focused on the relationship
      between acculturation (often measured by a shift in language use) and health
      outcomes, paying less attention to network processes and the implications of
      interethnic integration for long-term health. This study frames English-language
      use among immigrants in the United States as a reflection of bridging social
      capital that is indicative of social network diversity. Using longitudinal data
      on self-rated health and the incidence of chronic conditions from the New
      Immigrant Survey (2003, 2007), I examine the contemporaneous and longitudinal
      associations between interethnic social capital and health. The results show
      evidence for a positive long-term effect of linguistic integration on health
      status, but no cross-sectional associations were observed. Overall, these results
      highlight the possible role of network processes in linking English-language use
      with immigrant health and the time-dependent nature of the relationship between
      linguistic integration and health status.

PMID- 29462570
TI  - Maternal Perceptions of Infant Feeding and Health in the Context of the 2015
      Nepal Earthquake.
AB  - BACKGROUND: Displacement caused by the 2015 earthquake in Nepal exacerbated poor
      health and nutrition for thousands of women and children. Research aim: This
      study aimed to identify the perceptions of Nepalese mothers residing in
      earthquake relocation camps regarding barriers, facilitators, and situational
      factors influencing breastfeeding and family well-being. METHODS: An exploratory,
      rapid ethnographic approach was used during two fieldwork phases. Phase 1
      consisted of reconnaissance and observation, whereas Phase 2 consisted of
      observation and qualitative semistructured interviews with infant caretakers ( N
      = 14). RESULTS: We found evidence of human milk substitutes donated by various
      groups after the earthquake, despite Nepal's media statement condemning these
      donations. Participants in this study expressed concerns about their milk supply.
      They also expressed concerns about the impending winter season combined with
      distress about the 2015 fuel crisis and the impact that this had on their infants
      and children. Furthermore, participants expressed choices about infant feeding
      that were influenced by traditional Nepalese practices. Specifically, homemade
      complementary foods and spices designed to boost lactation were identified as
      being used during daily infant feeding practices. CONCLUSION: Infant caretakers
      need culturally specific support for breastfeeding after disasters. These
      findings can directly influence future interventions concerning Nepalese mothers'
      perceptions, infant care, and feeding practices in disaster scenarios.

PMID- 29462571
TI  - Elucidating the Burden of HIV in Tissues Using Multiplexed Immunofluorescence and
      In Situ Hybridization: Methods for the Single-Cell Phenotypic Characterization of
      Cells Harboring HIV In Situ.
AB  - Persistent tissue reservoirs of HIV present a major barrier to cure. Defining
      subsets of infected cells in tissues is a major focus of HIV cure research.
      Herein, we describe a novel multiplexed in situ hybridization (ISH) (RNAscope)
      protocol to detect HIV-DNA (vDNA) and HIV-RNA (vRNA) in formalin-fixed paraffin
      embedded (FFPE) human tissues in combination with immunofluorescence (IF)
      phenotyping of the infected cells. We show that multiplexed IF and ISH (mIFISH)
      is suitable for quantitative assessment of HIV vRNA and vDNA and that
      multiparameter IF phenotyping allows precise identification of the cellular
      source of the ISH signal. We also provide semi-quantitative data on the impact of
      various tissue fixatives on the detectability of vDNA and vRNA with RNAscope
      technology. Finally, we describe methods to quantitate the ISH signal on whole
      slide digital images and validation of the quantitative ISH data with
      quantitative real-time PCR for vRNA. It is our hope that this approach will
      provide insight into the biology of HIV tissue reservoirs and to inform
      strategies aimed at curing HIV.

PMID- 29462572
TI  - Lactobacilli and bifidobacteria ameliorate memory and learning deficits and
      oxidative stress in beta-amyloid (1-42) injected rats.
AB  - The gastrointestinal microbiota affects brain function, including memory and
      learning. In this study we investigated the effects of probiotics on memory and
      oxidative stress biomarkers in an experimental model of Alzheimer's disease.
      Sixty rats were randomly divided into 5 groups: control; control-probiotics,
      which received probiotics for 8 weeks; sham operation, which received an
      intrahippocampal injection of phosphate-buffered saline; Alzheimer, which
      received an intrahippocampal injection of beta-amyloid (Abeta1-42); and Alzheimer
      probiotics, which in addition to being injected with Abeta1-42, received 2 g (1 *
      1010 CFU/g) of probiotics (Lactobacillus acidophilus, L. fermentum,
      Bifidobacterium lactis, and B. longum) for 8 weeks. Memory and learning were
      measured using the Morris water maze, and oxidative stress biomarkers in the
      hippocampus were measured using ELISA kits. Morris water maze results indicated
      that compared with the Alzheimer group, the Alzheimer-probiotics group had
      significantly improved spatial memory, including shorter escape latency and
      travelled distance and greater time spent in the target quadrant. There was also
      improvement in oxidative stress biomarkers such as increased malondialdehyde
      levels and superoxide dismutase activity following the beta-amyloid injection.
      Overall, it seems that probiotics play a role in improving memory deficit and
      inhibiting the pathological mechanisms of Alzheimer's disease by modifying
      microbiota.

PMID- 29462574
TI  - Adiponectin receptor agonist AdipoRon decreased ceramide, and lipotoxicity, and
      ameliorated diabetic nephropathy.
AB  - BACKGROUND: Adiponectin is known to take part in the regulation of energy
      metabolism. AdipoRon, an orally-active synthetic adiponectin agonist, binds to
      both adiponectin receptors (AdipoR)1/R2 and ameliorates diabetic complications.
      Among the lipid metabolites, the ceramide subspecies of sphingolipids have been
      linked to features of lipotoxicity, including inflammation, cell death, and
      insulin resistance. We investigated the role of AdipoRon in the prevention and
      development of type 2 diabetic nephropathy. METHODS: AdipoRon (30 mg/kg) was
      mixed into the standard chow diet and provided to db/db mice (db + AdipoRon, n =
      8) and age-matched male db/m mice (dm + AdipoRon, n = 8) from 17 weeks of age for
      4 weeks. Control db/db (db cont, n = 8) and db/m mice (dm cont, n = 8) were fed a
      normal diet of mouse chow. RESULTS: AdipoRon-fed db/db mice showed a decreased
      amount of albuminuria and lipid accumulation in the kidney with no significant
      changes in serum adiponectin, glucose, and body weight. Restoring expression of
      adiponectin receptor-1 and -2 in the renal cortex was observed in db/db mice with
      AdipoRon administration. Consistent up-regulation of phospho-Thr172 AMP-dependent
      kinase (AMPK), peroxisome proliferative-activated receptor alpha (PPARalpha),
      phospho-Thr473 Akt, phospho-Ser79Acetyl-CoA carboxylase (ACC), and phospho
      Ser1177 endothelial NO synthase (eNOS), and down-regulation of protein
      phosphatase 2A (PP2A), sterol regulatory element-binding protein-1c (SREBP-1c),
      and inducible nitric oxide synthase (iNOS) were associated within the same group.
      AdipoRon lowered cellular ceramide levels by activation of acid ceramidase, which
      normalized ceramide to sphingosine-1 phosphate (S1P) ratio. In glomerular
      endothelial cells (GECs) and podocytes, AdipoRon treatment markedly decreased
      palmitate-induced lipotoxicity, which ultimately ameliorated oxidative stress and
      apoptosis. CONCLUSIONS: AdipoRon may prevent lipotoxicity in the kidney
      particularly in both GECs and podocytes through an improvement in lipid
      metabolism, as shown by the ratio of ceramide to sphingosines, and further
      contribute to prevent deterioration of renal function, independent of the
      systemic effects of adiponectin. The reduction in oxidative stress and apoptosis
      by AdipoRon provides protection against renal damage, thereby ameliorating
      endothelial dysfunction in type 2 diabetic nephropathy.

PMID- 29462575
TI  - Insect jumping springs.
AB  - A quick guide to the springs used by insects to achieve remarkable feats of
      jumping.

PMID- 29462576
TI  - Dumbo octopod hatchling provides insight into early cirrate life cycle.
AB  - Cirrate octopods (Cephalopoda: Cirrata) are among the largest invertebrates of
      the deep sea. These organisms have long been known to lay single, large egg
      capsules on hard substrates on the ocean bottom [1], including cold-water
      octocorals (Anthozoa: Octocorallia). The egg capsule is comprised of an external
      egg case as well as the chorion and developing embryo. Development in cirrates
      proceeds for an extended time without parental care [2]. Although juveniles have
      previously been collected in the midwater [3], cirrate hatchlings have so far
      never been observed. Here, we provide the first video of a living hatchling and
      use magnetic resonance imaging (MRI) to analyze its anatomy and assign the
      specimen to the genus Grimpoteuthis, the so-called dumbo octopods. The specimen's
      behavior and advanced state of organ development show that cirrate hatchlings
      possess all morphological features required for movement via fin-swimming, for
      visually and chemically sensing their environment, and for prey capture. In
      addition, the presence of a large internal yolk sac reduces the risk of failure
      at first feeding. These data provide evidence that dumbo octopods hatch as
      competent juveniles.

PMID- 29462577
TI  - Gut glands illuminate trunk segmentation in Cambrian fuxianhuiids.
AB  - The euarthropod body consists of serially repeated segments with various degrees
      of functional specialization and regionalization [1]. Some representatives
      exhibit deviant metameric patterns expressed as an indirect correspondence
      between components of the exoskeleton, usually the number or position of
      dorsoventral sclerotized plates and walking legs (Supplemental Information) [1
      3]. Segmental mismatch in the form of supernumerary walking legs per tergite
      (i.e. dorsal exoskeletal plate) is characteristic of fuxianhuiids, Cambrian
      euarthropods widely regarded as critical for understanding the origin of this
      phylum [4,5]. The broader significance of this organization remains obscure,
      however, due to the difficulty of distinguishing which components of the
      fuxianhuiid trunk reflect ancestral or derived traits. Here, we describe for the
      first time the presence of metameric midgut diverticulae in Fuxianhuia protensa
      from the Chengjiang Konservat-Lagerstatte and demonstrate that these digestive
      structures follow the segmentation pattern of the dorsal exoskeleton. Midgut
      diverticulae signal a predatory or scavenging ecology [6,7], falsifying the view
      of fuxianhuiids as simple mud-feeders [4]. Comparison with other euarthropods [1
      3,5] indicates that fuxianhuiids possessed a unique mode of exoskeletal and
      visceral segmental mismatch, in which the tergites and midgut were segmentally
      patterned independently from the walking legs and ventral nerve cord. Our
      findings provide direct evidence of substantial developmental flexibility among
      stem-group euarthropods during the Cambrian.

PMID- 29462578
TI  - Insect Vision: Judging Distance with Binocular Motion Disparities.
AB  - Praying mantises, like humans, calculate distance by triangulating angular
      disparities of corresponding image regions between their eyes. New work shows
      they can do this using just dynamic luminance changes, and thus judge distance in
      scenes that we see as flat.

PMID- 29462579
TI  - Visual Perception: To Curve or Not to Curve.
AB  - A popular new illusion shows that the apparent curvature of sinusoidal contours
      depends on contrast and background luminance. We suggest that the illusion is
      driven by segmentation mechanisms of human vision, which isolate the contours
      into smaller segments, some which approximate straight lines, others curves.

PMID- 29462580
TI  - Comparative Cognition: Rats Pay Back Quid Pro Quo.
AB  - Humans engage in exchanges of commodities or services, often paying back a
      commodity with a different service. New research suggests that rats can
      reciprocally trade food for allogrooming, and vice versa.

PMID- 29462581
TI  - Immunology: Is Actin at the Lytic Synapse a Friend or a Foe?
AB  - Cytotoxic T cells and natural killer cells defend us against disease by secreting
      lytic granules. Whether actin facilitates or thwarts lytic granule secretion has
      been an open question. Recent results now indicate that the answer depends on the
      maturation stage of the immune cell-target cell contact.

PMID- 29462582
TI  - Sensory Neuroscience: Linking Dopamine, Expectation, and Hallucinations.
AB  - Psychosis is associated with a dysregulation of the brain's dopamine-mediated
      neurotransmitter system. Yet, specific mechanisms underlying psychotic symptoms
      are not well understood. A new study has now uncovered a dopamine-dependent
      mechanism that explains why psychotic patients experience hallucinations.

PMID- 29462583
TI  - Cognitive Science: Persistent Apes Are Intelligent Apes.
AB  - In humans, self-control is correlated with general intelligence; a new study
      finds that this correlation extends to chimpanzees as well. The new results
      highlight the cognitive bases of self-control and suggest a common evolutionary
      history for human and primate self-control.

PMID- 29462584
TI  - Evolution: Vertebrate Limb Control over 420 Million Years.
AB  - The neural circuits that control elasmobranch fins and the mammalian limbs have
      been found to exhibit striking similarities at the molecular, cellular and
      behavioral levels. The implication is that the neural substrate underlying limb
      control had already evolved 420 million years ago.

PMID- 29462585
TI  - Social Behavior: Bonobos Are Nice but Prefer Mean Guys.
AB  - Human infants prefer to interact with prosocial individuals. Bonobos, our close
      relatives, however, prefer antisocial individuals, perhaps due to a preference
      for social dominance. Human prosocial behavior may be due to unique tendencies to
      positively evaluate prosocial others.

PMID- 29462586
TI  - Sociobiology: Changing the Dominance Hierarchy.
AB  - One fundamental question is to understand what neural circuits are involved when
      social hierarchies are established, maintained and modified. Now, a new study
      shows that a previously subordinate animal can become dominant after optogenetic
      stimulation of the dorsomedial prefrontal cortex, demonstrating that this brain
      region is necessary and sufficient to quickly induce winning during social
      competitions.

PMID- 29462587
TI  - Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance.
AB  - The maintenance of a healthy and functional mitochondrial network is critical
      during development as well as throughout life in the response to physiological
      adaptations and stress conditions. Owing to their role in energy production,
      mitochondria are exposed to high levels of reactive oxygen species, making them
      particularly vulnerable to mitochondrial DNA mutations and protein misfolding.
      Given that mitochondria are formed from proteins encoded by both nuclear and
      mitochondrial genomes, an additional layer of complexity is inherent in the
      coordination of protein synthesis and the mitochondrial import of nuclear-encoded
      proteins. For these reasons, mitochondria have evolved multiple systems of
      quality control to ensure that the requisite number of functional mitochondria
      are present to meet the demands of the cell. These pathways work to eliminate
      damaged mitochondrial proteins or parts of the mitochondrial network by mitophagy
      and renew components by adding protein and lipids through biogenesis,
      collectively resulting in mitochondrial turnover. Mitochondrial quality control
      mechanisms are multi-tiered, operating at the protein, organelle and cell levels.
      Herein, we discuss mitophagy in different physiological contexts and then relate
      it to other quality control pathways, including the unfolded protein response,
      shedding of vesicles, proteolysis, and degradation by the ubiquitin-proteasome
      system. Understanding how these pathways contribute to the maintenance of
      mitochondrial homeostasis could provide insights into the development of targeted
      treatments when these systems fail in disease.

PMID- 29462588
TI  - Posttranslational modification of heme in peroxidases - Impact on structure and
      catalysis.
AB  - Four heme peroxidase superfamilies arose independently in evolution. Only in the
      peroxidase-cyclooxygenase superfamily the prosthetic group is posttranslationally
      modified (PTM). As a consequence these peroxidases can form one, two or three
      covalent bonds between heme substituents and the protein. This may include ester
      bonds between heme 1- and 5-methyl groups and glutamate and aspartate residues as
      well as a sulfonium ion link between the heme 2-vinyl substituent and a
      methionine. Here the phylogeny and physiological roles of representatives of this
      superfamily, their occurrence in all kingdoms of life, the relevant sequence
      motifs for definite identification and the available crystal structures are
      presented. We demonstrate the autocatalytic posttranslational maturation process
      and the impact of the covalent links on spectral and redox properties as well as
      on catalysis, including Compound I formation and reduction by one- and two
      electron donors. Finally, we discuss the evolutionary advantage of these PTMs
      with respect to the proposed physiological functions of the metalloenzymes that
      range from antimicrobial defence in innate immunity to extracellular matrix
      formation and hormone biosynthesis.

PMID- 29462589
TI  - Potentiation of skin TSLP production by a cosmetic colorant leads to aggravation
      of dermatitis symptoms.
AB  - Certain cosmetic colorants are irritant to skin or aggravate dermatitis. Thymic
      stromal lymphopoietin (TSLP) plays an important role in the initiation and
      progress of skin inflammation and atopic dermatitis by triggering Th2 immune
      responses. However, the effects of cosmetic colorants on TSLP production are
      unknown yet. Therefore, we investigated whether cosmetic colorants regulated TSLP
      production and dermatitis. Lithol Rubine B (LR-B, Pigment Red 57) and its calcium
      salt (LR-BCA), commonly used cosmetic colorants, potentiated phorbol-12-myristate
      13-acetate-induced TSLP production in keratinocytes. In addition, the topical
      exposure to LR-B or LR-BCA on mouse ear upregulated a TSLP inducer (MC903)
      induced TSLP production and Th2 cytokine expression. Dermatitis symptoms and
      serum IgE and histamine levels were also aggravated by LR-B or LR-BCA,
      implicating the role of increased TSLP expression in acute dermatitis. LR-B or LR
      BCA induced IkappaBalpha degradation and NF-kappaB activation in keratinocytes,
      leading to TSLP expression. Collectively, our results demonstrate that LR-B and
      LR-BCA increase TSLP expression and Th2 immune responses, thereby aggravating
      acute dermatitis in the compromised skin. The results further suggest that
      certain cosmetic colorants such as LR-B may aggravate dermatitis under pro
      inflammatory conditions by upregulating TSLP production.

PMID- 29462590
TI  - Lipid bilayer stress in obesity-linked inflammatory and metabolic disorders.
AB  - The maintenance of the characteristic lipid compositions and physicochemical
      properties of biological membranes is essential for their proper function.
      Mechanisms allowing to sense and restore membrane homeostasis have been
      identified in prokaryotes for a long time and more recently in eukaryotes. A
      membrane remodeling can result from aberrant metabolism as seen in obesity. In
      this review, we describe how such lipid bilayer stress can account for the
      modulation of membrane proteins involved in the pathogenesis of obesity-linked
      inflammatory and metabolic disorders. We address the case of the Toll-like
      receptor 4 that is implicated in the obesity-related low grade inflammation and
      insulin resistance. The lipid raft-mediated TLR4 activation is promoted by an
      enrichment of the plasma membrane with saturated lipids or cholesterol increasing
      the lipid phase order. We discuss of the plasma membrane Na, K-ATPase that
      illustrates a new concept according to which direct interactions between specific
      residues and particular lipids determine both stability and activity of the pump
      in parallel with indirect effects of the lipid bilayer. The closely related
      sarco(endo)-plasmic Ca-ATPase embedded in the more fluid ER membrane seems to be
      more sensitive to a lipid bilayer stress as demonstrated by its inactivation in
      cholesterol-loaded macrophages or its inhibition mediated by an increased
      PtdCho/PtdEtn ratio in obese mice hepatocytes. Finally, we describe the model
      recently proposed for the activation of the conserved IRE-1 protein through
      alterations in the ER membrane lipid packing and thickness. Such IRE-1 activation
      could occur in response to abnormal lipid synthesis and membrane remodeling as
      observed in hepatocytes exposed to excess nutrients. Since the IRE-1/XBP1 branch
      also stimulates the lipid synthesis, this pathway could create a vicious cycle
      "lipogenesis-ER lipid bilayer stress-lipogenesis" amplifying hepatic ER pathology
      and the obesity-linked systemic metabolic defects.

PMID- 29462591
TI  - Survival Rates After Lobectomy, Segmentectomy, and Wedge Resection for Non-Small
      Cell Lung Cancer.
AB  - BACKGROUND: This study aimed to compare the survival rates after lobectomy,
      segmentectomy, and wedge resection for the eighth edition of the tumor, node,
      metastasis classification for stage IA non-small cell lung cancer (NSCLC).
      METHODS: Patients who underwent lobectomy, segmentectomy, or wedge resection for
      stage IA NSCLC were identified from the Surveillance, Epidemiology, and End
      Results database. A Cox regression model and propensity-matched analysis were
      used. The overall survival (OS) rates and lung cancer-specific survival (LCSS)
      rates among the three groups were compared by tumor size. RESULTS: A total of
      16,819 patients met our criteria. Although the OS rate was better for lobectomy
      than for wedge resection, no statistical differences in the LCSS rate were
      identified among the three treatment groups of patients with tumors that were 1.0
      cm or smaller. For tumors from 1.1 to 2.0 cm, lobectomy and segmentectomy showed
      no statistical differences in the LCSS rate, but both conferred better OS and
      LCSS rates than wedge resection. For tumors from 2.1 to 3.0 cm, the OS and LCSS
      rates were better for lobectomy than for segmentectomy or wedge resection, but
      similar for segmentectomy and wedge resection. CONCLUSIONS: Lobectomy,
      segmentectomy, and wedge resection are comparable oncologic procedures for
      patients with stage IA NSCLC that is 1.0 cm or smaller. For tumors from 1.1 to
      2.0 cm, lobectomy and segmentectomy could lead to equivalent survival rates but
      showed better survival rates than that observed with wedge resection. For tumors
      from 2.1 to 3.0 cm, lobectomy is still the standard surgical procedure; for
      patients who are unsuitable candidates for lobectomy, segmentectomy and wedge
      resection show similar survival rates.

PMID- 29462592
TI  - Platelet-lymphocyte ratio acts as an independent predictor of prognosis in
      patients with renal cell carcinoma.
AB  - BACKGROUND: The prognostic value of plated-lymphocyte ratio (PLR) in multiple
      malignancies had been investigated in previous studies; however, its prognostic
      value in renal cell carcinoma (RCC) remains controversial. This study was
      performed to assess the prognostic value of preoperative PLR in RCC patients.
      METHODS: Literature was searched from PubMed, Embase, Web of Science and Cochrane
      database, which evaluated the relationships between preoperative PLR and
      prognosis in RCC patients. Hazard ratios (HRs) for overall survival (OS) and
      progression-free survival (PFS) were extracted from eligible studies.
      Heterogeneity was assessed using the I2 value. The fixed-effects model was used
      if there was no evidence of heterogeneity; otherwise, the random-effects model
      was used. Publication bias was evaluated using Begg's funnel plots and Egger's
      regression test. RESULTS: A total of 1528 patients from seven studies were
      included in the analysis. The pooled analysis showed that an elevated PLR was an
      effective prognostic marker of both OS (pooled HR = 2.10, 95%CI: 1.38-3.19, p =
      0.001) and PFS (pooled HR = 3.45, 95%CI: 1.61-7.40, p = 0.001). Subgroup analysis
      revealed that a high PLR significantly predicted worse OS and PFS in Asian
      studies (OS, pooled HR = 2.72, 95%CI: 1.06-7.03, p = 0.038; PFS, pooled HR = 6.0,
      95%CI: 3.12-11.54, p < 0.001), in metastatic RCC patients receiving mixed
      therapies (OS, pooled HR = 3.69, 95%CI: 1.93-11.42, p = 0.023; PFS, pooled HR =
      6.05, 95%CI: 1.34-27.37, p = 0.019) and targeted therapy (OS, pooled HR = 1.59,
      95%CI: 0.97-2.62, p = 0.067), in sample size >100 (OS, pooled HR = 1.83, 95%CI:
      1.49-2.25, p < 0.001; PFS pooled HR = 6.05, 95%CI: 1.34-27.37, p < 0.019), and in
      cut-off value of PLR <= 195 (OS, pooled HR = 3.65, 95%CI: 1.06-12.60, p = 0.04;
      PFS pooled HR 4.46, 95%CI: 1.68-11.87, p = 0.003). CONCLUSIONS: This study
      suggests that a high preoperative PLR is correlated with poor prognosis in RCC
      patients.

PMID- 29462593
TI  - Carboxymethylated chitosan protects Schwann cells against hydrogen peroxide
      induced apoptosis by inhibiting oxidative stress and mitochondria dependent
      pathway.
AB  - Carboxymethylated chitosan (CMCS) has many beneficial effects, including anti
      oxidant and anti-apoptotic actions. However, the mechanisms by which CMCS protect
      against oxidative stress induced damage to Schwann cells (SCs) remains unclear.
      The present study aimed to investigate the mechanism by which CMCS protects SCs
      against hydrogen peroxide (H2O2) induced damage. H2O2 was used to establish a
      model of oxidative stress injury in SCs to mimic the development of nerve injury
      in vitro. Different concentrations (50, 100 and 200 ug/ml) of CMCS were added to
      test whether CMCS was capable of protecting SCs from H2O2 induced damage. MTT,
      LDH release and Annexin V/FITC assays were then performed. Levels of reactive
      oxygen species were detected using a reactive oxygen species assay kit, the
      mitochondrial membrane potential (DeltaPsim) of SCs was analyzed by rhodamine123
      fluorescence staining, the synthesis of Bcl-2, Bax, cytochrome c and caspase-3
      were analyzed by real-time PCR and Western blot analysis. The results showed that
      CMCS protected SCs from apoptosis, decreased LDH release and enhanced cell
      viability, also decreased reactive oxygen species levels and increased DeltaPsim.
      Additional experiments demonstrated that CMCS could decrease protein expression
      of Bax, cytochrome c and caspase-3, while promote Bcl-2 protein expression
      induced by H2O2. Taken together, the finding of this study indicated that CMCS
      prevented H2O2-induced damage to SCs through the mitochondrial dependent pathway.

PMID- 29462595
TI  - Simultaneous detection of Mycoplasma pneumoniae IgG and IgM using dual-label time
      resolved fluoroimmunoassay.
AB  - Anti-Mycoplasma pneumoniae (MP) IgM and IgG are useful serological markers for
      detection of MP infection. In this study, a simultaneous quantification of MP IgM
      and IgG was performed by time-resolved fluoroimmunoassay (TRFIA). The europium
      labeled anti-human IgM and samarium-labeled anti-human IgG were used as tracers,
      and MP IgM and IgG were recognized in serum samples. After dissociating europium
      and samarium ions from the immune complex, their fluorescence intensity was
      recorded and used to calculate the concentrations. The linear range and
      sensitivity of detection were 2-5500 BU/mL and 0.5 BU/mL for IgM, and 1.5-1500
      BU/mL and 0.2 BU/mL for IgG, respectively. The intra- and inter-assay
      coefficients of variation were 5.14% and 8.41% for IgM, and 5.44% and 8.76% for
      IgG, respectively. The recovery rate was 94.9-106.8% for IgM and 96.1-109.4% for
      IgG. The correlation rates of serum detection for 38 respiratory infected
      patients between dual-label TRFIA and ELISA were 0.9294 and 0.9366 for IgM and
      IgG, respectively. The coincidence rate between passive particle agglutination
      and TRFIA is 93.3%. Dual-label TRFIA is a sensitive and reliable technique for
      measuring MP IgM and IgG levels and could be useful for the early diagnosis of MP
      infection.

PMID- 29462594
TI  - Melatonin promotes neuroprotection of induced pluripotent stem cells-derived
      neural stem cells subjected to H2O2-induced injury in vitro.
AB  - Melatonin is a neurohormone mainly extracted from the pineal gland with
      neuroprotective effects. It has antioxidant, anti-inflammatory, and antiapoptotic
      functions. However, the mechanism of melatonin against reactive oxygen species is
      unclear. Here, we explore the potential proliferative and neuroprotective
      mechanism of melatonin on induced pluripotent stem cells (iPSC)-derived neural
      stem cells (NSCs) exposed to hydrogen peroxide (H2O2). NSCs were induced from
      iPSCs, then pretreated with 500 MUM H2O2, 1 MUM melatonin, 1 MUM melatonin
      receptor antagonist (Luzindole), or 10 MUM Phosphatidylinositide 3 kinase (PI3K)
      inhibitor (LY294002). The results showed that melatonin stimulated proliferation
      of iPSC-derived NSCs on H2O2 exposure. Melatonin also markedly improved
      stabilization of the mitochondrial membrane potential and reduced the rate of
      apoptosis. Treatment with Luzindole or LY294002 inhibited the increasing
      proliferative and neuroprotective effects of melatonin on iPSC-derived NSCs with
      H2O2 treatment. Our results further demonstrated that these promotional effects
      of melatonin were related with the activity of phosphorylation of AKT. Therefore,
      these outcomes propose that melatonin protects iPSC-derived NSCs from H2O2
      induced injury through the mediation of melatonin receptor and PI3K/AKT signaling
      pathway.

PMID- 29462596
TI  - Onabotulinumtoxin type A improves lower urinary tract symptoms and quality of
      life in patients with human T cell lymphotropic virus type 1 associated
      overactive bladder.
AB  - AIM: To evaluate the efficacy of the onabotulinum toxin type A in the treatment
      of HTLV-1 associated overactive bladder and its impact on quality of life (QoL).
      METHODS: Case series with 10 patients with overactive bladder refractory to
      conservative treatment with anticholinergic or physical therapy. They received
      200Ui of onabotulinumtoxin type A intravesically and were evaluated by overactive
      bladder symptoms score (OABSS) and King's Health Questionnaire. RESULTS: The mean
      (SD) of the age was 52+14.5 years and 60% were female. All of them had confirmed
      detrusor overactivity on urodynamic study. Seven patients had HAM/TSP. The median
      and range of the OABSS was 13 (12-15) before therapy and decreased to 1.0 (0-12)
      on day 30 and to 03 (0-14) on day 90 (p<0.0001). There was a significant
      improvement in 8 of the 9 domains of the King's Health Questionnaire after the
      intervention. Hematuria, urinary retention and urinary infection were the
      complications observed in 3 out of 10 patients. The mean time to request
      retreatment was 465 days. CONCLUSION: Onabotulinum toxin type A intravesically
      reduced the OABSS with last long effect and improved the quality of life of HTLV
      1 infected patients with severe overactive bladder.

PMID- 29462597
TI  - Validity and Reliability of Outcome Measures Assessing Dexterity, Coordination,
      and Upper Limb Strength in Autosomal Recessive Spastic Ataxia of Charlevoix
      Saguenay.
AB  - OBJECTIVE: To document in adults affected by autosomal recessive spastic ataxia
      of Charlevoix-Saguenay (ARSACS) the intra- and interrater reliability, standard
      error of measurement, agreement, minimal detectable change, and construct
      validity of the 9-Hole Peg Test (NHPT), the Standardized Finger-to-Nose Test
      (SFNT), and grip strength. DESIGN: Metrologic study. SETTING: Neuromuscular
      rehabilitation clinic. PARTICIPANTS: Genetically confirmed adult patients with
      ARSACS (N=42; 21 women; mean age, 38.6y). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Intra- and interrater reliability was determined using the
      intraclass correlation coefficient (ICC). Construct validity was determined by
      assessing the capacity of the NHPT, the SFNT, and grip strength to distinguish
      between participants based on sex, mobility stages, and age groups, and on
      performance on the Archimedes spiral and fast alternating hand movements tests.
      RESULTS: All 3 tests have shown excellent reliability (ICC=.90-.98). However, the
      limit of agreement was influenced by the participant's performance on the NHPT,
      and the minimal detectable change was very different for both hands (right=9.7 vs
      left=28.0). Construct validity was confirmed for the SFNT and NHPT, but it was
      not demonstrated for grip strength. CONCLUSIONS: Given the metrologic properties
      assessed in this study, the SFNT is an excellent measure to assess upper limb
      coordination, whereas the NHPT must be used with caution. The grip strength is
      reliable but does not seem to reflect disease severity.

PMID- 29462598
TI  - Using adult Aedes aegypti females to predict areas at risk for dengue
      transmission: A spatial case-control study.
AB  - INTRODUCTION: Traditional indices for measuring dengue fever risk in a given area
      are based on the immature forms of the vector (larvae and pupae surveys).
      However, this is inefficient because only adult female mosquitoes actually
      transmit the virus. Based on these assumptions, our objective was to evaluate the
      association between an entomological index obtained from adult mosquito traps and
      the occurrence of dengue in a hyperendemic area. Additionally, we compared its
      cost to that of the Breteau Index (BI). MATERIAL AND METHODS: We performed this
      study in Sao Jose do Rio Preto, SP, Brazil, between the epidemiological weeks of
      36/2012 and 19/2013. BG-Sentinel and BG-Mosquitito traps were installed to
      capture adult mosquitoes. Positive and negative cases of dengue fever were
      computed and geocoded. We generated biweekly thematic maps of the entomological
      index, generated by calculating the number of adult Aedes aegypti females (NAF)
      per 100 households during a week by kriging, and based on the number of
      mosquitoes captured. The relation between the occurrence of dengue fever and the
      NAF was tested using a spatial case-control design and a generalized additive
      model and was controlled by the coordinates of the positive and negative cases of
      dengue fever. RESULTS: Our analyses showed that increases in dengue fever cases
      occurred in parallel with increases in the number of Ae. aegypti females. The
      entomological index produced in our study correlates positively with the
      incidence of dengue, particularly during intervals when vector control measures
      were applied less intensively. The operational costs of our index were lower than
      those of the BI: NAF used 71.5% less human resources necessary to measure the BI.
      CONCLUSIONS: Spatial analysis techniques and the number of adult Ae. aegypti
      females were used to produce an indicator of dengue risk. The index can be
      applied at various levels of spatial aggregation for an entire study area, as
      well as for sub-areas, such as city blocks. Even though the index is adequate to
      predict dengue risk, it should be tested and validated in various scenarios
      before routine use.

PMID- 29462599
TI  - Involvement of 11-ketotestosterone in hooknose formation in male pink salmon
      (Oncorhynchus gorbuscha) jaws.
AB  - Mature male Pacific salmon (Oncorhynchus spp.) develop a hooknose, as a secondary
      male sexual characteristic, during the spawning period. It is likely that
      androgens regulate hooknose formation. However, endocrinological and
      histochemical details about the relationship between androgens and hooknose
      formation are poorly understood. In this study, we performed assays of serum
      androgens, detection of androgen receptor (AR) in hooknose tissues, external
      morphological measurement of hooknose-related lengths, and microscopic
      observation of hooknose tissues of pink salmon (O. gorbuscha) at different stages
      of sexual maturation. Expression of the arbeta gene was detected in hooknose
      tissues of males but not females. The elongation of these tissues was mediated
      directly via androgens. Serum 11-ketotestosterone (11-KT) concentrations
      indicated a significant positive correlation with both jaw lengths during sexual
      maturation of males. In the upper jaw, cartilage tissue developed during hooknose
      formation, and AR-immunoreactive chondrocytes were located in the rostal-vetral
      regions of hooknose cartilage in maturing male. The chondrocytes in maturing
      males before entering into rivers exhibited rich-cytoplasm with high cell
      activity than at other sexual development stages. On the other hand, in the lower
      jaw, the development of the spongiosa-like bone meshworks. AR-immunoreactivity
      was detected in a proportion of the osteocytes and osteoblast-like cells in the
      spongiosa-like bone meshworks. These results indicate that hooknose formation in
      pink salmon, which is associated with the buildup of a structure with sufficient
      strength that it can be used to attack other males on the spawning ground, is
      regulated by 11-KT.

PMID- 29462600
TI  - Snow cover and snowfall impact corticosterone and immunoglobulin a levels in a
      threatened steppe bird.
AB  - Birds use both the corticosterone stress response and immune system to meet
      physiological challenges during exposure to adverse climatic conditions. To
      assess the stress level and immune response of the Asian Great Bustard during
      conditions of severe winter weather, we measured fecal corticosterone (CORT) and
      Immunoglobulin A (IgA) before and after snowfall in a low snow cover year (2014)
      and a high snow cover year (2015). A total of 239 fecal samples were gathered
      from individuals in Tumuji Nature Reserve, located in eastern Inner Mongolia,
      China. We observed high CORT levels that rose further after snowfall both in high
      and low snow cover years. IgA levels increased significantly after snowfall in
      the low snow cover year, but decreased after snowfall in the high snow cover
      year. These results suggest that overwintering Asian Great Bustards are subjected
      to climatic stress during severe winter weather, and the hypothalamic-pituitary
      adrenal axis and immune system react to this challenge. Extreme levels of stress,
      such as snowfall in already prolonged and high snow cover conditions may decrease
      immune function. Supplemental feeding should be considered under severe winter
      weather conditions for this endangered subspecies.

PMID- 29462602
TI  - 6-Shogaol induces caspase-independent paraptosis in cancer cells via proteasomal
      inhibition.
AB  - An alpha, beta-unsaturated carbonyl compound of ginger, 6-Shogaol (6S), induced
      extensive cytoplasmic vacuolation and cell death in breast cancer cell (MDA-MB
      231) and non-small lung cancer (A549) cells. In the presence of autophagic
      inhibitors the cells continued to exhibit cytoplasmic vacuolation and cell death
      clearly distinguishing it from the classic autophagic process. 6S induced death
      did not exhibit the characteristic apoptotic features like caspase cleavage,
      phosphatidyl serine exposure and DNA fragmentation. The immunofluorescence with
      the Endoplasmic Reticulum (ER) resident protein, calreticulin indicated that the
      vacuoles were of ER origin, typical of paraptosis. This was supported by the
      increase in level of microtubule associated protein light chain 3B (LC3 I and LC3
      II) and polyubiquitin binding protein, p62. The level of ER stress markers like
      polyubiquitinated proteins, Bip and CHOP also consistently increased. We have
      found that 6S inhibits the 26S proteasome. The proteasomal inhibitory activity
      was elucidated by a) molecular docking of 6S onto the active site of beta5
      subunit and b) reduced fluorescence by the fluorogenic substrate of the
      chymotrypsin-like subunit. In conclusion these studies demonstrate for the first
      time that proteasomal inhibition by 6S induces cell death via paraptosis. So 6
      shogaol may act as a template for anti-cancer lead discovery against the
      apoptosis resistant cancer cells.

PMID- 29462601
TI  - Novel Developments in Endoscopic Mucosal Imaging.
AB  - Endoscopic techniques such as high-definition and optical-chromoendoscopy have
      had enormous impact on endoscopy practice. Since these techniques allow
      assessment of most subtle morphological mucosal abnormalities, further
      improvements in endoscopic practice lay in increasing the detection efficacy of
      endoscopists. Several new developments could assist in this. First, web based
      training tools could improve the skills of the endoscopist for enhancing the
      detection and classification of lesions. Secondly, incorporation of computer
      aided detection will be the next step to raise endoscopic quality of the captured
      data. These systems will aid the endoscopist in interpreting the increasing
      amount of visual information in endoscopic images providing real-time objective
      second reading. In addition, developments in the field of molecular imaging open
      opportunities to add functional imaging data, visualizing biological parameters,
      of the gastrointestinal tract to white-light morphology imaging. For the
      successful implementation of abovementioned techniques, a true multi-disciplinary
      approach is of vital importance.

PMID- 29462603
TI  - LOX-1 receptor: A potential link in atherosclerosis and cancer.
AB  - Altered production of reactive oxygen species (ROS), causing lipid peroxidation
      and DNA damage, contributes to the progression of atherosclerosis and cancer.
      Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a lectin-like
      receptor for oxidized low-density lipoproteins (ox-LDL) primarily expressed in
      endothelial cells and vasculature-rich organs. LOX-1 receptors is a marker for
      atherosclerosis, and once activated by ox-LDL or other ligands, stimulates the
      expression of adhesion molecules, pro-inflammatory signaling pathways and
      proangiogenic proteins, including NF-kB and VEGF, in vascular endothelial cells
      and macrophages. Several different types of cancer reported LOX-1 gene
      upregulation, and numerous interplays exist concerning LOX-1 in atherosclerosis,
      metabolic diseases and cancer. One of them involves NF-kB, an oncogenic protein
      that regulates the transcription of several inflammatory genes response. In a
      model of cellular transformation, the MCF10A ER-Src, inhibition of LOX-1 gene
      reduces NF-kB activation and the inflammatory and hypoxia pathways, suggesting a
      mechanistic connection between cellular transformation and atherosclerosis. The
      remodeling proteins MMP-2 and MMP-9 have been found increased in angiogenesis in
      atherosclerotic plaque and also in human prostate cancer cells. In this review,
      we outlined the role of LOX-1 in atherogenesis and tumorigenesis as a potential
      link in these diseases, suggesting that LOX-1 inhibition could represent a
      promising strategy in the treatment of atherosclerosis and tumors.

PMID- 29462604
TI  - Enhanced detection of infectious prions by direct ELISA from the brains of
      asymptomatic animals using DRM2-118 monoclonal antibody and Gdn-HCl.
AB  - In this report we describe the use of a novel anti-prion monoclonal antibody
      (DRM2-118) for the direct detection of infectious prions by ELISA. Epitope
      mapping using overlapping hamster (SHa) prion peptides indicates DRM2-118 binding
      occurs between residues 93-100 and at the 310-helix (residues 163-170) between
      alpha helix-A and -B. This antibody shows broad species binding to endogenous
      prions from brain homogenates and corresponding recombinant prion proteins. To
      evaluate the performance of this MAb for the detection of prion proteins we
      performed an animal time course and evaluated prion detection from both crude
      brain homogenates and lipid raft fractions (DRM) by direct ELISA. Prion detection
      was significantly enhanced by the addition of the chaotropic guanidine-HCl (Gdn
      HCl) during protein immobilization with detection of PK-resistant prion from
      asymptomatic animal brains at (45-DPI) and from lipid rafts at (24-DPI). Our data
      demonstrates enhanced prion detection from brain lipid rafts of asymptomatic
      animals by a simple direct ELISA using the DRM2-118 MAb combined with Gdn-HCl.

PMID- 29462605
TI  - Performance evaluation of phage-displayed synthetic human single-domain antibody
      libraries: A retrospective analysis.
AB  - Fully human synthetic single-domain antibodies (sdAbs) are desirable therapeutic
      molecules but their development is a considerable challenge. Here, using a
      retrospective analysis of in-house historical data, we examined the parameters
      that impact the outcome of screening phage-displayed synthetic human sdAb
      libraries to discover antigen-specific binders. We found no evidence for a
      differential effect of domain type (VH or VL), library randomization strategy,
      incorporation of a stabilizing disulfide linkage or sdAb display format
      (monovalent vs. multivalent) on the probability of obtaining any antigen-binding
      human sdAbs, instead finding that the success of library screens was primarily
      related to properties of target antigens, especially molecular mass. The
      solubility and binding affinity of sdAbs isolated from successful screens
      depended both on properties of the sdAb libraries (primarily domain type) and the
      target antigens. Taking attrition of sdAbs with major manufacturability concerns
      (aggregation; low expression) and sdAbs that do not recognize native cell-surface
      antigens as independent probabilities, we calculate the overall likelihood of
      obtaining >=1 antigen-binding human sdAb from a single library-target screen as
      ~24%. Successful library-target screens should be expected to yield ~1.3 human
      sdAbs on average, each with average binding affinity of ~2 MUM.

PMID- 29462606
TI  - Limb remote ischemic post-conditioning mitigates brain recovery in a mouse model
      of ischemic stroke by regulating reactive astrocytic plasticity.
AB  - Maladaptive alterations of astrocytic plasticity may cause brain edema in the
      acute stage of stroke and glial scar formation in the recovery stage. The present
      study was designed to investigate the potential regulation of limb remote
      ischemic post-conditioning (RIPC) on astrocytic plasticity in experimental
      cerebral ischemia-reperfusion injury. Cerebral ischemia was induced by transient
      middle cerebral artery occlusion (tMCAO) for 1 h in C57BL/6 mice, who were
      treated with RIPC immediately after reperfusion. The results showed that RIPC
      decreased hemispheric swelling, infarct volume and brain atrophy, and increased
      neurological function recovery and survival rates of ischemic mice at 3 and 14 d
      after cerebral ischemia-reperfusion, respectively. Moreover, the proportion of
      astrocyte subtypes was adjusted by RIPC treatment, demonstrated by decreased
      expression of the fibrous type (glial fibrillary acidic protein, GFAP) and
      increased expression of the protoplasmic type (glutamine synthetase, GS) in the
      ipsilateral side of the mouse brain at 14 d after cerebral ischemia-reperfusion.
      RIPC treatment adjusted the proportion of GFAP subtypes by downregulating the
      protein level of GFAPalpha, as well as upregulating the GFAPdelta/GFAPalpha ratio
      in the ipsilateral side at 3 and 14 d after reperfusion. Notably, RIPC inhibited
      the phosphorylation of signal transducer and activators of transcriptions 3 (p
      STAT3) in the ipsilateral side at 3 and 14 d after cerebral ischemia-reperfusion.
      Taken together, the results show that RIPC treatment could regulate reactive
      astrocytic plasticity and inhibition of STAT3 phosphorylation to promote
      neurological function recovery following ischemic stroke.

PMID- 29462607
TI  - Ascorbic acid ameliorates lead-induced apoptosis in the cerebellar cortex of
      developing rats.
AB  - We investigated the effects of the gestational administration of lead (Pb) and
      ascorbic acid on cerebellar development. Pregnant female rats were randomly
      assigned to the control, Pb, or Pb plus ascorbic acid (PA) groups; six offspring
      per cage were randomly selected for analysis. Compared to the control group,
      fewer Purkinje cells were observed in the Pb-exposed pups at postnatal day 21.
      However, co-administrating Pb and ascorbic acid inhibited the Pb-induced
      reduction in Purkinje cells. Terminal deoxynucleotidyl transferase-mediated dUTP
      nick end-labeling (TUNEL) staining, which detected DNA fragmentation in the dying
      cells, showed more TUNEL-positive cells in the Pb group, while co-treatment with
      Pb and ascorbic acid mitigated the Pb-induced cellular degeneration. Using
      immunohistochemistry and immunoblotting, we additionally found that Pb exposure
      induced a rise in the apoptotic factor Bax in the cerebellum, while Pb plus
      ascorbic acid treatment ameliorated this Bax induction. Since, Pb competes with
      the iron in the cell and the accumulation of free iron triggers oxidative stress,
      we performed iron staining, which revealed that ascorbic acid prevented the Pb
      induced rises in iron-reactive cells and iron-reactivity. The anti-oxidant enzyme
      manganese-dependent superoxide dismutase showed change patterns that were similar
      to those of iron in the cerebellum. Finally, the pups' blood Pb levels were
      highest in the Pb group but were reduced in the PA group. Our findings suggest
      that ascorbic acid effectively ameliorates Pb-induced apoptosis and oxidative
      stress in the cerebellum. The present results imply that ascorbic acid treatment
      during pregnancy may protect against Pb-mediated developmental impairments in the
      cerebellum.

PMID- 29462609
TI  - Contextual constraints on lexico-semantic processing in aging: Evidence from
      single-word event-related brain potentials.
AB  - The current study reports the effects of accumulating contextual constraints on
      neural indices of lexico-semantic processing (i.e., effects of word frequency and
      orthographic neighborhood) as a function of normal aging. Event-related brain
      potentials were measured from a sample of older adults as they read sentences
      that were semantically congruent, provided only syntactic constraints (syntactic
      prose), or were random word strings. A linear mixed-effects modeling approach was
      used to probe the effects of accumulating contextual constraints on N400
      responses to individual words. Like young adults in prior work, older adults
      exhibited a classic word position context effect on the N400 in congruent
      sentences, although the magnitude of the effect was reduced in older relative to
      younger adults. Moreover, by modeling single-word variability in N400 responses,
      we observed robust effects of orthographic neighborhood density that were larger
      in older adults than the young, and preserved effects word frequency.
      Importantly, in older adults, frequency effects were not modulated by
      accumulating contextual constraints, unlike in the young. Collectively, these
      findings indicate that older adults are less likely (or able) to use accumulating
      top-down contextual constraints, and therefore rely more strongly on bottom-up
      lexical features to guide semantic access of individual words during sentence
      comprehension.

PMID- 29462610
TI  - Spinal muscular atrophy: Selective motor neuron loss and global defect in the
      assembly of ribonucleoproteins.
AB  - Spinal muscular atrophy is caused by deletions or mutations in the SMN1 gene that
      result in reduced expression of the SMN protein. The SMN protein is an essential
      molecular chaperone that is required for the biogenesis of multiple
      ribonucleoprotein (RNP) complexes including spliceosomal small nuclear RNPs
      (snRNPs). Reductions in SMN expression result in a reduced abundance of snRNPs
      and to downstream RNA splicing alterations. SMN is also present in axons and
      dendrites and appears to have important roles in the formation of neuronal mRNA
      protein complexes during development or neuronal repair. Thus, SMA is an
      exemplar, selective motor neuron disorder that is caused by defects in
      fundamental RNA processing events. A detailed molecular understanding of how
      motor neurons fail, and why other neurons do not, in SMA will yield important
      principals about motor neuron maintenance and neuronal specificity in
      neurodegenerative diseases.

PMID- 29462611
TI  - MiR-29 family members interact with SPARC to regulate glucose metabolism.
AB  - MicroRNA (miR)-29 family members have been reported to play important regulatory
      roles in metabolic disease. We used TargetScan to show that "secreted protein
      acidic rich in cysteine" (SPARC) is a target of the miR-29s. SPARC is a
      multifunctional secretory protein involved in a variety of biological activities,
      and SPARC dysregulation is associated with a wide range of obesity-related
      disorders, including type 2 diabetes mellitus (T2DM). We explored whether miR-29s
      played roles in glucose metabolism and whether miR-29s directly targeted SPARC.
      We also examined the effect of SPARC on glucose metabolism and how the
      association of miR-29s with SPARC affected glucose metabolism. We found that
      overexpression of miR-29s reduced glucose uptake and GLUT4 levels; that miR-29
      directly targeted SPARC, resulting in degradation of SPARC-encoding mRNA and
      reduction in the SPARC protein level; that SPARC increased glucose uptake and
      GLUT4 levels; that shRNA-mediated knockdown of SPARC reduced GLUT4 protein levels
      in 3T3-L1 adipocytes; that miR-29s reduced glucose uptake and GLUT4 levels; and
      that miR-29s inhibited glucose uptake by suppressing SPARC synthesis. Thus, the
      miR-29 family negatively regulates glucose metabolism by inhibiting SPARC
      expression.

PMID- 29462612
TI  - N-terminus plus linker domain of Mg-chelatase D subunit is essential for Mg
      chelatase activity in Oryza sativa.
AB  - Mg chelatase, a key enzyme in chlorophyll biosynthesis, is comprised of I, D and
      H subunits. Among these subunits, the D subunit was regarded to mediate protein
      interactions due to its unique protein domains. However, the functional roles of
      the different domains of the D subunit in vivo remain unclear. In this study, we
      dissected the rice (Oryza sativa) D subunit (OsCHLD) into three peptide
      fragments: the putative chloroplast transit peptide (TP, Met1 to Arg45), the N
      terminus plus linker domain (OsCHLDN + L, Ala46 to Leu485) and the C-terminus
      (OsCHLDC, Ile486 to Ser754), to explore the roles of these fragments. The results
      of the yeast two-hybrid assay and the in vitro reconstitution of the Mg-chelatase
      activity showed that only OsCHLDN + L interacted with the I and H subunits and
      maintained most of the Mg-chelatase activity in vitro. Furthermore, artificial TP
      OsCHLDN + L and TP-OsCHLDC were overexpressed in rice. Interestingly, an
      incomplete co-suppression had occurred in both of the overexpressed (OsCHLDN + L
      ox and OsCHLDC-ox) plants, resulting in a significantly downregulated expression
      of endogenous OsCHLD. Therefore, these transgenic plants had adequate OsCHLDN + L
      and OsCHLDC instead of endogenous OsCHLD, providing ideal models to study the
      function of different domains of the D subunit in vivo. The OsCHLDN + L-ox plants
      showed an identical phenotype to that of the wild type, while the OsCHLDC-ox
      plants demonstrated a yellowish phenotype that resembled the D subunit mutants.
      These results indicated that only OsCHLDN + L could complement the function of
      endogenous OsCHLD, providing direct evidence that OsCHLDN + L is essential for Mg
      chelatase activity in vivo.

PMID- 29462608
TI  - mRNP assembly, axonal transport, and local translation in neurodegenerative
      diseases.
AB  - The development, maturation, and maintenance of the mammalian nervous system rely
      on complex spatiotemporal patterns of gene expression. In neurons, this is
      achieved by the expression of differentially localized isoforms and specific sets
      of mRNA-binding proteins (mRBPs) that regulate RNA processing, mRNA trafficking,
      and local protein synthesis at remote sites within dendrites and axons. There is
      growing evidence that axons contain a specialized transcriptome and are endowed
      with the machinery that allows them to rapidly alter their local proteome via
      local translation and protein degradation. This enables axons to quickly respond
      to changes in their environment during development, and to facilitate axon
      regeneration and maintenance in adult organisms. Aside from providing autonomy to
      neuronal processes, local translation allows axons to send retrograde injury
      signals to the cell soma. In this review, we discuss evidence that disturbances
      in mRNP transport, granule assembly, axonal localization, and local translation
      contribute to pathology in various neurodegenerative diseases, including spinal
      muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), frontotemporal
      dementia (FTD), and Alzheimer's disease (AD).

PMID- 29462613
TI  - Chlamydia pneumoniae infection promotes monocyte transendothelial migration by
      increasing vascular endothelial cell permeability via the tyrosine
      phosphorylation of VE-cadherin.
AB  - Migration of monocytes into the subendothelial layer of the intima is one of the
      critical events in early atherosclerosis. Chlamydia pneumoniae (C. pneumoniae)
      infection has been shown to promote monocyte transendothelial migration (TEM).
      However, the exact mechanisms have not yet been fully clarified. In this study,
      we tested the hypothesis that C. pneumoniae infection increases vascular
      endothelial cell (VEC) permeability and subsequent monocyte TEM through
      stimulating the tyrosine phosphorylation of vascular endothelial-cadherin (VE
      cadherin). Here, we demonstrated that C. pneumoniae infection promoted monocyte
      TEM in a TEM assay possibly by increasing the permeability of a VEC line EA.hy926
      cell as assessed by measuring the passage of FITC-BSA across a VEC monolayer.
      Subsequently, Western blot analysis showed that C. pneumoniae infection induced
      VE-cadherin internalization. Our further data revealed that Src-mediated VE
      cadherin phosphorylation at Tyr658 was involved in C. pneumoniae infection
      induced internalization of VE-cadherin, VEC hyperpermeability and monocyte TEM.
      Taken together, our data indicate that C. pneumoniae infection promotes monocyte
      TEM by increasing VEC permeability via the tyrosine phosphorylation and
      internalization of VE-cadherin in VECs.

PMID- 29462614
TI  - TGF-beta1/TbetaRII/Smad3 signaling pathway promotes VEGF expression in oral
      squamous cell carcinoma tumor-associated macrophages.
AB  - Oral squamous cell carcinoma (OSCC) is the most common type of malignant cancer
      affecting the oral cavity. Tumor associated macrophages (TAMs) play a vital role
      in the initiation, progression and metastasis of OSCC. In this study, we
      investigated the correlation between macrophages and several clinical and
      pathological indicators, and we also explored how transforming growth factor
      beta1 (TGF-beta1) effect on VEGF expression in TAMs. Seventy-two paraffin
      embedded OSCC samples were collected. Association between macrophages density,
      micro vascular density (MVD) and clinical-pathological feature were explored by
      immunohistochemical staining. Western blot, ELISA and qRT-PCR were conducted to
      assess the VEGF expression in TAMs treated with or without neutralizing TGF
      beta1, TbetaRII and smad3 antibodies. Results showed that CD68+ macrophages were
      absent in normal tissues. Macrophages density was directly correlated to low
      pathological differentiation, late clinical staging and poor survival rate. MVD
      showed positive correlation with clinical staging and macrophages density.
      Furthermore, OSCC-associated macrophages expressed more VEGF than macrophages in
      healthy lymph nodes. However, when TGF-beta1 or TbetaRII were neutralized or the
      Smad3 was inhibited, VEGF expression was down regulated as well. It is concluded
      that TGF-beta1 could promote OSCC-associated macrophages to secrete more VEGF via
      TbetaRII/Smad3 signaling pathway. This result might explain the correlation
      between macrophages density and worse clinical-pathological condition.

PMID- 29462615
TI  - Ubiquitin C-Terminal Hydrolase L1 regulates autophagy by inhibiting autophagosome
      formation through its deubiquitinating enzyme activity.
AB  - Ubiquitination modification has been shown to play a key role in autophagy.
      Increasing studies reported the involvement of de-ubiquitinating enzymes (DUBs)
      in autophagy pathway. To systematically search how DUBs manipulate autophagy, we
      utilized a double fluorescence tagged LC3 stable HeLa cell line, and did a genome
      wide screen of 55 human DUBs which is about 60% coverage of the DUB family. We
      found a bunch of DUBs have impact on autophagy by either changing the LC3 puncta
      formation or the autophagy flux. One of them, Ubiquitin C-Terminal Hydrolase L1
      (UCHL1) correlated to Parkinson's disease, strongly affects autophagy by
      inhibiting autophagosome formation. We found UCHL1 overexpression inhibits LC3
      puncta formation and is dependent on its DUB activity. Knockdown of UCHL1
      significantly promotes LC3 puncta formation. Further study revealed that UCHL1
      may affect autophagy by interacting with LC3 but not other autophagy related
      proteins. Interestingly, a Parkinson's disease related mutant UCHL1 I93 M defects
      its DUB activity and can no longer inhibit autophagosome formation. We further
      screened 22 commercially available DUB inhibitors and found two potent UCHL1
      inhibitors LDN-57444 (LDN) and NSC632839 (NSC), when treating cells, both
      strongly induce LC3 puncta formation. Taken together, our results indicated a new
      insight into the manner in which DUB regulates autophagy and provided potential
      drugs for the Parkinson's disease.

PMID- 29462616
TI  - A potential substrate binding pocket of BdcA plays a critical role in NADPH
      recognition and biofilm dispersal.
AB  - Biofilm dispersal is characterized by the cell detachment from biofilms and
      expected to provide novel "anti-biofilm" approaches of prevention and treatment
      of biofilms in clinical and industrial settings. The E.coli protein BdcA has been
      identified as a biofilm dispersal factor and designed to be an important
      component in engineered applications to control biofilm formation. It belongs to
      short-chain dehydrogenase/reductase (SDR) family with the specific affinity to
      NADPH. Here, we show the structure of BdcA in complex with NADPH and confirm that
      NADPH binding is requisite for BdcA facilitating cell motility and increasing
      biofilm dispersal. Especially, we observe a potential substrate binding pocket
      surrounded by hydrophobic residues upon NADPH binding and present evidences that
      this pocket is essential for BdcA binding NADPH and exerting its biological
      functions. Our study provides the clues for illuminating the molecular mechanism
      of BdcA regulating biofilm dispersal and better utilizing BdcA to eliminate the
      biofilms.

PMID- 29462618
TI  - Overexpression of Larp4B downregulates dMyc and reduces cell and organ sizes in
      Drosophila.
AB  - Regulation of cell and organ sizes is fundamental for all organisms, but its
      molecular basis is not fully understood. Here we performed a gain-of-function
      screen and identified larp4B whose overexpression reduces cell and organ sizes in
      Drosophila melanogaster. Larp4B is a member of La-related proteins (LARPs)
      containing an LA motif and an adjacent RNA recognition motif (RRM), and play
      diverse roles in RNA metabolism. However, the function of Larp4B has remained
      poorly characterized. We generated transgenic flies overexpressing wild-type
      Larp4B or a deletion variant lacking the LA and RRM domains, and demonstrated
      that the RNA-binding domains are essential for Larp4B to reduce cell and organ
      sizes. We found that the larp4B-induced phenotype was suppressed by dMyc
      overexpression, which promotes cell growth and survival. Furthermore,
      overexpression of larp4B decreased dMyc protein levels, whereas its loss-of
      function mutation had an opposite effect. Our results suggest that Larp4B is a
      negative regulator of dMyc.

PMID- 29462617
TI  - Effect of trichostatin A on Burkitt's lymphoma cells: Inhibition of EPS8 activity
      through Phospho-Erk1/2 pathway.
AB  - Histone deacetylase inhibitors (HDACi) manifest great potential for treatment of
      Burkitt's lymphoma (BL), an aggressive B-cell lymphoma. Epidermal growth factor
      receptor pathway substrate 8 (EPS8) is confirmed overexpressed and associated
      with poor prognosis in solid tumors and leukemia. However, EPS8 expression and
      the relationship between EPS8 and HDACi on BL remains obscure. Here, we
      hypothesized that trichostatin A (TSA), a pan-HDACi, could inhibit BL cells by
      downregulating EPS8. We demonstrated that TSA reduced cell viability, induced
      apoptosis and cell arrest at G0/G1. Mechanismly, TSA attenuated EPS8 and
      downstream Phospho-Erk1/2 pathway. Knockdown of EPS8 resulted in a significant
      reduction in cellular proliferation and suppressed Phospho-Erk1/2 pathway
      activity, particularly when combined with TSA. Conversely, overexpression of EPS8
      rescued this phenomenon. Then we showed that the combination of TSA and
      Epirubicin had a more significant effect when compared with TSA or Epirubicin
      alone. Finally, knockdown of EPS8 and TSA had a synergistic suppression effect on
      BALB/c nude mice. In conclusion, this study reveals that TSA affects BL cells by
      suppressing Phospho-Erk1/2 pathway through downregulating EPS8.

PMID- 29462619
TI  - Soluble dietary fiber improves energy homeostasis in obese mice by remodeling the
      gut microbiota.
AB  - Intervention with dietary fibers is an important strategy to combat the global
      epidemic of obesity which is a consequence of energy imbalance. However, a
      possible role of the gut microbiota in effects of dietary fibers on energy
      homeostasis remains unclear. Here, we treated a high fat diet-induced obese (DIO)
      mouse model with soluble dietary fiber. Our results showed that soluble dietary
      fiber reduced body weight gain and the excessive accumulation of white fat tissue
      in DIO mice. Notably, soluble dietary fiber increased energy expenditure, but not
      change energy intake in DIO mice. In accordance, 16S rRNA sequencing revealed
      that the diversity of the gut microbiota was restored by soluble dietary fiber.
      Moreover, compared with controls, soluble dietary fiber resulted in a decreased
      ratio of Firmicutes/Bacteroidetes at the phylum level, and an increased relative
      abundance of the genera Roseburia at the genus level. Taken together, these
      findings indicate that soluble dietary fiber improves energy homeostasis and
      prevents obesity by increasing the diversity of the gut microbiota and the
      colonization of beneficial bacteria.

PMID- 29462620
TI  - Human AK2 links intracellular bioenergetic redistribution to the fate of
      hematopoietic progenitors.
AB  - AK2 is an adenylate phosphotransferase that localizes at the intermembrane spaces
      of the mitochondria, and its mutations cause a severe combined immunodeficiency
      with neutrophil maturation arrest named reticular dysgenesis (RD). Although the
      dysfunction of hematopoietic stem cells (HSCs) has been implicated, earlier
      developmental events that affect the fate of HSCs and/or hematopoietic
      progenitors have not been reported. Here, we used RD-patient-derived induced
      pluripotent stem cells (iPSCs) as a model of AK2-deficient human cells.
      Hematopoietic differentiation from RD-iPSCs was profoundly impaired. RD-iPSC
      derived hemoangiogenic progenitor cells (HAPCs) showed decreased ATP distribution
      in the nucleus and altered global transcriptional profiles. Thus, AK2 has a stage
      specific role in maintaining the ATP supply to the nucleus during hematopoietic
      differentiation, which affects the transcriptional profiles necessary for
      controlling the fate of multipotential HAPCs. Our data suggest that maintaining
      the appropriate energy level of each organelle by the intracellular
      redistribution of ATP is important for controlling the fate of progenitor cells.

PMID- 29462621
TI  - Direct posttranslational modification of astrocytic connexin 43 proteins by the
      general anesthetic propofol in the cerebral cortex.
AB  - Propofol is widely used as a general anesthetic and is generally considered to
      exert its action by regulating neuronal firing via facilitation of GABAA
      receptors. However, accumulating evidence suggests that propofol also acts on
      astrocytes, including inhibitory effects on gap junctional coupling, but the
      underlying molecular mechanisms remain largely unknown. Here, using acute
      cortical brain slices prepared from mice, we characterize propofol-induced
      molecular changes in astrocytic gap junction protein connexin 43 (Cx43). Propofol
      does not change the protein expression level of Cx43 or its incorporation into
      gap junctional plaques, according to biochemical and immunohistochemical
      analyses. However, propofol alters migration pattern of Cx43 on western blot,
      suggesting changes in its posttranslational modifications. Indeed, this change is
      accompanied by an increase in the phosphorylation of Cx43 at serine 368, which is
      known to reduce permeability of Cx43 gap junctions. Finally, we show that this
      change occurs in the absence of neuronal firing or glutamatergic transmissions.
      Overall, these results show that propofol induces posttranslational modification
      of Cx43 directly on astrocytes at the site of gap junctional plaques, exerting
      direct pharmacological action on astrocytes in parallel with its action on
      neurons.

PMID- 29462622
TI  - Additional increased effects of mannitol-temozolomide combined treatment on blood
      brain barrier permeability.
AB  - The blood-brain barrier (BBB) is major obstacle in drug or stem cell treatment in
      chronic stroke. We hypothesized that adding mannitol to temozolomide (TMZ) is a
      practically applicable method for resolving the low efficacy of intravenous
      mannitol therapy. In this study, we investigated whether BBB permeability could
      be increased by this combined treatment. First, we established a chronic ischemic
      stroke rat model and examined changes in leakage of Evans blue dye within a
      lesion site, and in expression of tight junction proteins (TJPs), by this
      combined treatment. Additionally, in an in vitro BBB model using trans-wells, we
      analyzed changes in diffusion of a fluorescent tracer and in expression of TJPs.
      Mannitol-TMZ combined treatment not only increased the amount of Evans blue dye
      within the stroke lesion site, but also reduced occludin expression in rat brain
      microvessels. The in vitro study also showed that combined treatment increased
      the permeability for two different-sized fluorescent tracers, especially large
      size, and decreased expression of TJPs, such as occludin and ZO-1. Increased BBB
      permeability effects were more prominent with combined than with single
      treatments. Mannitol-TMZ combined treatment induced a decrease of TJPs with a
      consequent increase in BBB permeability. This combined treatment is clinically
      useful and might provide new therapeutic options by enabling efficient
      intracerebral delivery of various drugs that could not otherwise be used to treat
      many CNS diseases due to their inability to penetrate the BBB.

PMID- 29462623
TI  - Identification of matrix metalloproteinase 9-interacting sequences in
      staphylococcal superantigen-like protein 5.
AB  - Staphylococcal superantigen like 5 (SSL5) is an exotoxin produced by S. aureus
      and has a strong inhibitory effect on MMP-9 enzymatic activity. However, the
      mechanism of inhibition remains unclear. We sought to identify the responsible
      regions of SSL5 for the interaction with MMP-9 by comparing a series of domain
      swap and deletion mutants of SSL5. Binding analyses revealed that SSL5 had two
      regions for binding to MMP-9 catalytic domain, beta1-3 region (25SKELKNVTGY
      RYSKGGKHYL IFDKNRKFTR VQIFGK60) in N-terminal half and alpha4beta9 region
      (138KELDFKLRQY LIQNFDLYKK FPKDSKIKVI MKD170) in C-terminal half. The collagen
      binding domain and zinc-chelating histidine residues of MMP-9 were not essential
      for the specific binding to SSL5. The domain swap mutants of SSL5 that conserved
      beta1-3 but not alpha4beta9 region inhibited the gelatinolysis by MMP-9, and the
      mutant of SSL7 that substituted beta1-3 region to that of SSL5 acquired the
      binding and inhibitory activity. Furthermore, the polypeptide that harbored beta1
      3 region of SSL5 inhibited gelatinolysis by MMP-9. Taken together, SSL5 inhibits
      the MMP9 activity through binding to the catalytic domain, and the beta1-3 region
      is responsible for the inhibition of proteolytic activity of MMP-9.

PMID- 29462624
TI  - Human sperm swimming in a high viscosity mucus analogue.
AB  - Remarkably, mammalian sperm maintain a substantive proportion of their
      progressive swimming speed within highly viscous fluids, including those of the
      female reproductive tract. Here, we analyse the digital microscopy of a human
      sperm swimming in a highly viscous, weakly elastic mucus analogue. We exploit
      principal component analysis to simplify its flagellar beat pattern, from which
      boundary element calculations are used to determine the time-dependent flow field
      around the sperm cell. The sperm flow field is further approximated in terms of
      regularised point forces, and estimates of the mechanical power consumption are
      determined, for comparison with analogous low viscosity media studies. This
      highlights extensive differences in the structure of the flows surrounding human
      sperm in different media, indicating how the cell-cell and cell-boundary
      hydrodynamic interactions significantly differ with the physical
      microenvironment. The regularised point force decomposition also provides cell
      level information that may ultimately be incorporated into sperm population
      models. We further observe indications that the core feature in explaining the
      effectiveness of sperm swimming in high viscosity media is the loss of cell
      yawing, which is related with a greater density of regularised point force
      singularities along the axis of symmetry of the flagellar beat to represent the
      flow field. In turn this implicates a reduction of the wavelength of the distal
      beat pattern - and hence dynamical wavelength selection of the flagellar beat -
      as the dominant feature governing the effectiveness of sperm swimming in highly
      viscous media.

PMID- 29462625
TI  - Enhanced prediction of recombination hotspots using input features extracted by
      class specific autoencoders.
AB  - In yeast and in some mammals the frequencies of recombination are high in some
      genomic locations which are known as recombination hotspots and in the locations
      where the recombination is below average are consequently known as coldspots.
      Knowledge of the hotspot regions gives clues about understanding the meiotic
      process and also in understanding the possible effects of sequence variation in
      these regions. Moreover, accurate information about the hotspot and coldspot
      regions can reveal insights into the genome evolution. In the present work, we
      have used class specific autoencoders for feature extraction and reduction.
      Subsequently the deep features that are extracted from the autoencoders were used
      to train three different classifiers, namely: gradient boosting machines, random
      forest and deep learning neural networks for predicting the hotspot and coldspot
      regions. A comparative performance analysis was carried out by experimenting on
      deep features extracted from different sets of the training data using
      autoencoders for selecting the best set of deep features. It was observed that
      learning algorithms trained on features extracted from the combined class
      specific autoencoder out performed when compared with the performances of these
      learning algorithms trained with other sets of deep features. So the combined
      class-specific autoencoder based feature extraction can be applied to a growing
      range of biological problems to achieve superior prediction performance.

PMID- 29462626
TI  - An approach for reduction of false predictions in reverse engineering of gene
      regulatory networks.
AB  - A gene regulatory network discloses the regulatory interactions amongst genes, at
      a particular condition of the human body. The accurate reconstruction of such
      networks from time-series genetic expression data using computational tools
      offers a stiff challenge for contemporary computer scientists. This is crucial to
      facilitate the understanding of the proper functioning of a living organism.
      Unfortunately, the computational methods produce many false predictions along
      with the correct predictions, which is unwanted. Investigations in the domain
      focus on the identification of as many correct regulations as possible in the
      reverse engineering of gene regulatory networks to make it more reliable and
      biologically relevant. One way to achieve this is to reduce the number of
      incorrect predictions in the reconstructed networks. In the present
      investigation, we have proposed a novel scheme to decrease the number of false
      predictions by suitably combining several metaheuristic techniques. We have
      implemented the same using a dataset ensemble approach (i.e. combining multiple
      datasets) also. We have employed the proposed methodology on real-world
      experimental datasets of the SOS DNA Repair network of Escherichia coli and the
      IMRA network of Saccharomyces cerevisiae. Subsequently, we have experimented upon
      somewhat larger, in silico networks, namely, DREAM3 and DREAM4 Challenge
      networks, and 15-gene and 20-gene networks extracted from the GeneNetWeaver
      database. To study the effect of multiple datasets on the quality of the inferred
      networks, we have used four datasets in each experiment. The obtained results are
      encouraging enough as the proposed methodology can reduce the number of false
      predictions significantly, without using any supplementary prior biological
      information for larger gene regulatory networks. It is also observed that if a
      small amount of prior biological information is incorporated here, the results
      improve further w.r.t. the prediction of true positives.

PMID- 29462627
TI  - Embeddability of Kimura 3ST Markov matrices.
AB  - In this note, we characterize the embeddability of generic Kimura 3ST Markov
      matrices in terms of their eigenvalues. As a consequence, we are able to compute
      the volume of such matrices relative to the volume of all Markov matrices within
      the model. We also provide examples showing that, in general, mutation rates are
      not identifiable from substitution probabilities. These examples also illustrate
      that symmetries between mutation probabilities do not necessarily arise from
      symmetries between the corresponding mutation rates.

PMID- 29462628
TI  - Term small-for-gestational-age infants from low-risk women are at significantly
      greater risk of adverse neonatal outcomes.
AB  - BACKGROUND: Small-for-gestational-age infants (birthweight <0th centile) are at
      increased risk of perinatal complications but are frequently not identified
      antenatally, particularly in low-risk women delivering at term (>=37 weeks
      gestation). This is compounded by the fact that late pregnancy ultrasound is not
      the norm in many jurisdictions for this cohort of women. We thus investigated the
      relationship between birthweight <10th centile and serious neonatal outcomes in
      low-risk women at term. OBJECTIVE(S): We aimed to determine whether there is a
      difference of obstetric and perinatal outcomes for small-for-gestational-age
      infants, subdivided into fifth to <10th centile and less than the fifth centile
      cohorts compared with an appropriate-for-gestational age (birthweight 10th-90th
      centile) group at term. STUDY DESIGN: This was a retrospective analysis of data
      from the Mater Mother's Hospital in Brisbane, Australia, for women who delivered
      between January 2000 and December 2015. Women with multiple pregnancy, diabetes
      mellitus, hypertension, preterm birth, major congenital anomalies, and large for
      gestational age infants (>90th centile for gestational age) were excluded. Small
      for-gestational-age infants were subdivided into 2 cohorts: infants with
      birthweights from the fifth to <10th centile and those less than the fifth
      centile. Serious composite neonatal morbidity was defined as any of the
      following: Apgar score <=3 at 5 minutes, respiratory distress syndrome, acidosis,
      admission into the neonatal intensive care unit, stillbirth, or neonatal death.
      Univariate and multivariate analyses were performed using generalized estimating
      equations to compare obstetric and perinatal outcomes for small-for-gestational
      age infants compared with appropriate-for-gestational age controls. RESULTS: The
      final study comprised 95,900 infants. Five percent were between the fifth and
      <10th centiles for birthweight and 4.3% were less than the fifth centile. The
      rate of serious composite neonatal morbidity was 11.1% in the control group,
      13.7% in the fifth and <10th centile, and 22.6% in the less than the fifth
      centile cohorts, respectively. Even after controlling for confounders, both the
      fifth to <10th centiles and less than the fifth centile cohorts were at
      significantly increased risk of serious composite neonatal morbidity compared
      with controls (odds ratio, 1.25, 95% confidence interval, 1.15-1.37, and odds
      ratio, 2.20, 95% confidence interval, 2.03-2.39, respectively). Infants with
      birthweights <10th centile were more likely to have severe acidosis at birth, 5
      minute Apgar score <=3 and to be admitted to the neonatal intensive care unit.
      The serious composite neonatal morbidity was higher in infants less than the
      fifth centile compared with those in the fifth to <10th centile cohort (odds
      ratio, 1.71, 95% confidence interval, 1.52-1.92). The odds of perinatal death
      (stillbirth and neonatal death) were significantly higher in both small-for
      gestational age groups than controls. After stratification for gestational age at
      birth, the composite outcome remained significantly higher in both small-for
      gestational-age cohorts and was highest in the less than the fifth centile group
      at 37+0 to 38+6 weeks (odds ratio, 3.32, 95% confidence interval, 2.87-3.85). The
      risk of perinatal death was highest for infants less than the fifth centile at
      37+0 to 38+6 weeks (odds ratio, 5.50, 95% confidence interval, 2.33-12.98).
      CONCLUSION: Small-for-gestational-age infants from term, low-risk pregnancies are
      at significantly increased risk of mortality and morbidity when compared with
      appropriate-for-gestational age infants. Although this risk is increased at all
      gestational ages in infants less than the fifth centile for birthweight, it is
      highest at early-term gestation. Our findings highlight that early-term birth
      does not necessarily improve outcomes and emphasize the importance of identifying
      this cohort of infants.

PMID- 29462629
TI  - A prospective study of risk-based colposcopy demonstrates improved detection of
      cervical precancers.
AB  - BACKGROUND: Sensitivity for detection of precancers at colposcopy and reassurance
      provided by a negative colposcopy are in need of systematic study and
      improvement. OBJECTIVE: We sought to evaluate whether selecting the appropriate
      women for multiple targeted cervical biopsies based on screening cytology, human
      papillomavirus testing, and colposcopic impression could improve accuracy and
      efficiency of cervical precancer detection. STUDY DESIGN: In all, 690 women aged
      18-67 years referred to colposcopy subsequent to abnormal cervical cancer
      screening results were included in the study (ClinicalTrials.gov: NCT00339989).
      Up to 4 cervical biopsies were taken during colposcopy to evaluate the
      incremental benefit of multiple biopsies. Cervical cytology, human papillomavirus
      genotyping, and colposcopy impression were used to establish up to 24 different
      risk strata. Outcomes for the primary analysis were cervical precancers, which
      included p16+ cervical intraepithelial neoplasia 2 and all cervical
      intraepithelial neoplasia 3 that were detected by colposcopy-guided biopsy during
      the colposcopy visit. Later outcomes in women without cervical intraepithelial
      neoplasia 2+ at baseline were abstracted from electronic medical records.
      RESULTS: The risk of detecting precancer ranged from 2-82% across 24 strata based
      on colposcopy impression, cytology, and human papillomavirus genotyping. The risk
      of precancer in the lowest stratum increased only marginally with multiple
      biopsies. Women in the highest-risk strata had risks of precancer consistent with
      immediate treatment. In other risk strata, multiple biopsies substantially
      improved detection of cervical precancer. Among 361 women with cervical
      intraepithelial neoplasia <2 at baseline, 195 (54%) had follow-up cytology or
      histology data with a median follow-up time of 508 days. Lack of detection of
      precancer at initial colposcopy that included multiple biopsies predicted low
      risk of precancer during follow-up. CONCLUSION: Risk assessment at the colposcopy
      visit makes identification of cervical precancers more effective and efficient.
      Not finding precancer after a multiple-biopsy protocol provides high reassurance
      and allows releasing women back to regular screening.

PMID- 29462630
TI  - Pitfalls in assessing chorioamnionicity: novel observations and literature
      review.
AB  - Accurate diagnosis of chorioamnionicity in multiple pregnancies is the key to
      appropriate clinical management of multiple gestation. Although prenatal
      ultrasound assessment of chorioamnionicity is well established and highly
      accurate if performed in early pregnancy, exceptions and artifacts arise from
      anatomic variations in multiple pregnancies and unusual sonographic features do
      exist. We have summarized our own experiences and reports from the literature on
      these pitfalls as follows: (1) discordant fetal sex in monochorionic pregnancies
      due to sex chromosome abnormalities, genital malformation in 1 fetus, or
      dizygotic twins forming a monochorionic placenta; (2) separate placental masses
      in monochorionic pregnancies due to bipartite placenta; (3) false-negative and
      false-positive lambda sign can arise for various reasons, and in partial
      monochorionic/dichorionic placentas both T and lambda sign may co-exist; (4)
      intrauterine synechia appearing as a thick and echogenic intrauterine septum may
      lead to erroneous diagnosis of dichorionic twins; and (5) errors in ascertaining
      amnionicity by the visualization of thin intertwin amniotic membranes and the
      number of yolk sacs. The ultrasound techniques to reduce inaccuracy in prenatal
      determination of chorioamnionicity and the use of single nucleotide polymorphisms
      based on noninvasive prenatal test to determine zygosity are also reviewed.

PMID- 29462631
TI  - Rapidly Dissolving Microneedle Patches for Transdermal Iron Replenishment
      Therapy.
AB  - The prevalence of iron deficiency anemia (IDA) is predominant in women and
      children especially in developing countries. The disorder affects cognitive
      functions and physical activity. Although oral iron supplementation and
      parenteral therapy remains the preferred choice of treatment, gastric side
      effects and risk of iron overload decreases adherence to therapy. Transdermal
      route is an established approach, which circumvents the side effects associated
      with conventional therapy. In this project, an attempt was made to investigate
      the use of rapidly dissolving microneedles loaded with ferric pyrophosphate (FPP)
      as a potential therapeutic approach for management of IDA. Microneedle array
      patches were made using the micromolding technique and tested in vitro using rat
      skin to check the duration required for dissolution/disappearance of needles. The
      ability of FPP-loaded microneedles to replenish iron was investigated in anemic
      rats. Rats were fed iron-deficient diet for 5 weeks to induce IDA following which
      microneedle treatment was initiated. Recovery of rats from anemic state was
      monitored by measuring hematological and biochemical parameters. Results from in
      vivo study displayed significant improvements in hemoglobin and serum iron levels
      after 2-week treatment with FPP-loaded microneedles. The study effectively
      demonstrated the potential of microneedle-mediated iron replenishment for
      treatment of IDA.

PMID- 29462632
TI  - Water Activity and Its Significance in Topical Dosage Forms.
AB  - Unique properties of thermodynamic activity of solvents in topical semisolids and
      its effects on in vitro product performance have not been fully understood.
      Mechanistic investigation was undertaken to demonstrate the significance of
      thermodynamic potential of solvents [water activity (aw) or solvent activity
      (as)] on in vitro performance of model topical formulations. Drug transport
      across synthetic membranes was found to decrease with decreasing water activity
      of formulations. Similarly, in vitro permeation of model permeant (caffeine)
      across porcine epidermis was found to decrease with decreasing water activity of
      formulations. Notably, relatively low water activity formulations (aw, 0.78)
      induced dehydration in porcine skin associated with significant structural
      changes like detachment of individual stratum corneum layers. Inclusion of
      hydrating agents (propylene glycol) in low water activity (aw, 0.78) formulations
      restored hydration levels and structural integrity of porcine skin. Most
      importantly, incremental inclusion of propylene glycol in low water activity
      formulations (aw, 0.78) enhanced in vitro permeation of model permeant
      (fluorescein sodium). Further investigation revealed that variability in
      processing conditions (high shear mixing during emulsification step) could
      modulate water activity in semisolid formulations despite their compositional
      sameness. In retrospect, water activity was found to be a critical quality
      attribute of topical semisolid products which impacts overall product performance
      and drug delivery.

PMID- 29462633
TI  - Improved Stability of Tuberculosis Drug Fixed-Dose Combination Using Isoniazid
      Caffeic Acid and Vanillic Acid Cocrystal.
AB  - The classic fixed-dose combination (FDC) of 4 tuberculosis drugs, namely
      rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol
      dihydrochloride (EDH) has the twin issues of physical stability and RIF cross
      reaction in the 4-FDC. The major reason for these quality issues is the
      interaction between RIF and INH to yield isonicotinyl hydrazone in drug tablets.
      Pharmaceutical cocrystals of INH with caffeic acid (CFA) (PZA + EDH + RIF + INH
      CFA cocrystal) and vanillic acid (VLA) (PZA + EDH + RIF + INH-VLA cocrystal) are
      able to stabilize the FDC formulation compared with the reference batch (PZA +
      EDH + RIF + INH). Stability studies under accelerated humidity and temperature
      stress conditions of 40 degrees C and 75% relative humidity showed that the
      physical stability of the cocrystal formulation was superior by powder X-ray
      diffraction and scanning electron microscopy analysis, and chemical purity was
      analyzed by high-performance liquid chromatography. Changes in the composition
      and structure were monitored on samples drawn at 7, 15, 22, and 30 days of
      storage. FDC-INH-CFA cocrystal batch exhibited greater stability compared with
      FDC-INH-VLA cocrystal and FDC reference drug batches. The superior stability of
      INH-CFA cocrystal is attributed to the presence of stronger hydrogen bonds and
      cyclic O-H?O synthon in the crystal structure.

PMID- 29462634
TI  - Labrasol(r) and Salts of Medium-Chain Fatty Acids Can Be Combined in Low
      Concentrations to Increase the Permeability of a Macromolecule Marker Across
      Isolated Rat Intestinal Mucosae.
AB  - In addition to their solubilizing properties, excipients used in lipid-based
      formulations can improve intestinal permeability of macromolecules. We determined
      whether admixing of medium-chain fatty acid (MCFA) permeation enhancers with a
      lipoidal excipient (Labrasol(r)) could potentiate transepithelial flux of a
      poorly permeable macromolecule (fluorescein isothiocyanate dextran 4 kDa [FD4])
      across rat intestinal mucosae mounted in Ussing chambers. Low concentrations of
      sodium caprate (C10), sodium undecylenate (C11:1), or sodium laurate (C12)
      combined with Labrasol(r) increased the apparent permeability coefficient (Papp)
      of FD4 to values typically seen with higher concentrations of MCFAs or
      Labrasol(r) alone. For example, combination of C11:1 (0.5 mg/mL) with Labrasol(r)
      (1 mg/mL) increased the Papp of FD4 by 10- and 11-fold over the respective
      individual agents at the same concentrations where no enhancement was evident.
      The increased enhancement ratios seen with the combinations were associated with
      some perturbation in intestinal histology and with attenuation of an epithelial
      functional measure, carbachol-stimulated inward short-circuit current. In
      conclusion, combining three MCFAs separately with Labrasol(r) increased the Papp
      of FD4 to values greater than those seen for MCFAs or Labrasol(r) alone.
      Ultimately, this may permit lower concentrations of MCFA to be used in
      combination with other excipients in oral formulations of poorly permeable
      molecules.

PMID- 29462636
TI  - Remembering a pioneer of environmental health science: Colleagues honor Bernard
      "Bernie" Weiss (1925-2018)-a remarkable scientist, thinker, visionary and writer.

PMID- 29462635
TI  - Inhibition of Organic Anion Transporting Polypeptide 1B1 and 1B3 by Betulinic
      Acid: Effects of Preincubation and Albumin in the Media.
AB  - Betulinic acid (BA), a plant-derived pentacyclic triterpenoid, may interact with
      the members of the organic anion transporting polypeptide 1B subfamily. Here, we
      investigated the interactions of BA and its analogs with OATP1B1/3 and rat
      Oatp1b2 in vitro and in vivo. BA inhibited the activity of OATP1B1/3 and rat
      Oatp1b2 in vitro. Systemic exposure of atorvastatin was substantially altered
      with the intravenous co-administration of BA (20 mg/kg). Preincubation
      (incubation with inhibitors, followed by washout) with BA led to a sustained
      inhibition of OATP1B3, which recovered rapidly in the media containing 10% fetal
      bovine serum. The addition of albumin to the media decreased intracellular
      concentrations of BA and expedited the recovery of OATP1B3 activity following
      preincubation. For asunaprevir and cyclosporin A (previously known to inhibit
      OATP1B3 upon preincubation), the addition of albumin to the media shortened
      recovery time with asunaprevir, but not with cyclosporin A. Overall, our results
      showed that BA inhibits OATP1B transporters in vitro and may incur hepatic
      transporter-mediated drug interactions in vivo. Our results identify BA as
      another OATP1B3 inhibitor with preincubation effect and suggest that the
      preincubation effect and its duration is impacted by altered equilibrium of
      inhibitors between intracellular and extracellular space (e.g., albumin in the
      media).

PMID- 29462637
TI  - Biomarkers of immune tolerance in liver transplantation.
AB  - The liver exhibits intrinsic immune tolerogenic properties that contribute to a
      unique propensity toward spontaneous acceptance when transplanted, both in animal
      models and in humans. Thus, in contrast to what happens after transplantation of
      other solid organs, several years following liver transplantation a significant
      subset of patients are capable of maintaining normal allograft function with
      histological integrity in the absence of immunosuppressive drug treatment.
      Significant efforts have been put into identifying sensitive and specific
      biomarkers of tolerance in order to stratify liver transplant recipients
      according to their need for immunosuppressive medication and their likelihood of
      being able to completely discontinue it. These biomarkers are currently being
      validated in prospective clinical trials of immunosuppression withdrawal both in
      Europe and in the United States. These studies have the potential to transform
      the clinical management of liver transplant recipients by mitigating, at least in
      part, the burden of lifelong immunosuppression.

PMID- 29462638
TI  - Docosahexaenoic acid improves motor function in the model of spinal cord injury.
AB  - The present study demonstrates that docosahexaenoic acid (DHA, 22:6n-3) injected
      subcutaneously leads to recovery of locomotor functions observed within 5 weeks
      after traumatic spinal cord injury. This activity is confirmed by improving of
      BBB locomotor rating scale indicators. We assume that this activity is related to
      (1) enhancement of remyelination process, (2) proliferative activity, (3)
      antioxidant activity, (4) increase in GFAP staining and (5) enhancement of
      vimentin expression. In general, the results of the study show that DHA has a
      complex effect on post-traumatic central nervous system recovery, indicating its
      high therapeutic potential.

PMID- 29462639
TI  - Inhibition or facilitation? Modulation of corticospinal excitability during motor
      imagery.
AB  - Motor imagery (MI) is the mental simulation of an action without any overt
      movement. Functional evidences show that brain activity during MI and motor
      execution (ME) largely overlaps. However, the role of the primary motor cortex
      (M1) during MI is controversial. Effective connectivity techniques show a
      facilitation on M1 during ME and an inhibition during MI, depending on whether an
      action should be performed or suppressed. Conversely, Transcranial Magnetic
      Stimulation (TMS) studies report facilitatory effects during both ME and MI. The
      present TMS study shed light on MI mechanisms, by manipulating the instructions
      given to the participants. In both Experimental and Control groups, participants
      were asked to mentally simulate a finger-thumb opposition task, but only the
      Experimental group received the explicit instruction to avoid any unwanted
      fingers movements. The amplitude of motor evoked potentials (MEPs) to TMS during
      MI was compared between the two groups. If the M1 facilitation actually pertains
      to MI per se, we should have expected to find it, irrespective of the
      instructions. Contrariwise, we found opposite results, showing facilitatory
      effects (increased MEPs amplitude) in the Control group and inhibitory effects
      (decreased MEPs amplitude) in the Experimental group. Control experiments
      demonstrated that the inhibitory effect was specific for the M1 contralateral to
      the hand performing the MI task and that the given instructions did not
      compromise the subjects' MI abilities. The present findings suggest a crucial
      role of motor inhibition when a "pure" MI task is performed and the subjects are
      explicitly instructed to avoid overt movements.

PMID- 29462640
TI  - Blood biomarkers in paediatric mild traumatic brain injury: a systematic review.
AB  - OBJECTIVE: To summarize all current studies focusing on blood biomarkers in
      paediatric mild traumatic brain injury (mTBI) and to outline the possible use of
      blood biomarkers for diagnostic, prognostic and monitoring purposes within this
      setting. METHODS: A systematic review following the PRISMA guidelines was
      conducted using the MEDLINE, PubMed and EMBASE databases. RESULTS: A total of 21
      studies were included in the review, encompassing a total of 14 different
      biomarkers. Seventeen (81%) of these studies found a significant association
      between biomarker concentration and mTBI characteristics, however results from
      studies to date are diverse and at times conflicting. CONCLUSION: GFAP appears to
      be a promising blood biomarker for the prognosis and monitoring of mTBI, whereas
      UCH-L1 appears more promising at mTBI diagnosis. Despite this, the overall
      heterogeneity in assessed biomarkers, study design and measurement tools has made
      drawing specific conclusions challenging. Future research will require more
      uniform study design and methodological approaches to allow for the comparison,
      corroboration and validation of blood biomarkers within the context of paediatric
      mTBI.

PMID- 29462641
TI  - Predicting neurodevelopmental outcome in preterm born infants using auditory
      event-related potentials: A systematic review.
AB  - Prematurity is a known risk factor for later cognitive deficits. At present there
      are neither behavioral nor neurological tests available to detect those preterm
      infants who would benefit most from early interventions. Neurophysiologic
      methods, and more specifically, auditory event-related potentials (AERPs) are
      convenient tools to investigate early cognitive functioning. However, the
      capability of AERPs as a prognostic factor for mental development in preterm
      infants remains unclear. The present systematic search of the literature yielded
      1016 articles, out of which 13 were included. Both prospective and cross
      sectional studies reported a relationship between AERPs and cognitive outcome.
      Our results show that larger amplitudes and shorter latencies of late AERPs are
      related to better cognitive outcomes. Additional studies are needed to
      corroborate our findings regarding this potential use of AERPs in the individual
      evaluation of preterm born infants.

PMID- 29462642
TI  - Memory performance, global cerebral volumes and hippocampal subfield volumes in
      long-term survivors of Out-of-Hospital Cardiac Arrest.
AB  - AIM: We explored the associations between global brain volumes, hippocampal
      subfield volumes and verbal memory performance in long-term survivors of out-of
      hospital cardiac arrest (OHCA). METHODS: Three months after OHCA, survivors and
      healthy, age-matched controls were assessed with cerebral MRI and the California
      Verbal Learning Test-II (CVLT-II). Volumetric brain segmentation was performed
      automatically by FreeSurfer. RESULTS: Twenty-six OHCA survivors who were living
      independently in regular homes at the time of assessment and 19 controls
      participated in the study. Thirteen of the survivors had been conscious upon
      arrival to the emergency department. The other 13 survivors had 0.5-7 days of
      inpatient coma before recovery. Memory was poorer in the OHCA group that had been
      comatose beyond initial hospital admission compared to both other groups. Total
      cortical volumes, total hippocampus volumes and several hippocampal subfield
      volumes were significantly smaller in the OHCA group comatose beyond initial
      hospital admission compared to controls. No significant differences between the
      OHCA group conscious upon emergency department arrival and the other two groups
      were found for brain volumes. No significant differences were observed between
      any groups for white matter or total subcortical volumes. In OHCA survivors with
      recovery from inpatient coma, the various CVLT-II trials were significantly, but
      differentially, correlated to total gray matter volume, cortical volume and the
      hippocampal subfield subiculum. CONCLUSION: In this small, single-site study,
      both hippocampal volume and cortical volume were smaller in good outcome OHCA
      survivors 3 months after resuscitation in comparison to healthy controls. Smaller
      cerebral volumes were correlated with poorer memory performance.

PMID- 29462643
TI  - Pirouetting pigs: A large non-primate animal model based on unilateral 6
      hydroxydopamine lesioning of the nigrostriatal pathway.
AB  - INTRODUCTION: The rotating 6-hydroxydopamine (6-OHDA) rat model has long been
      important when developing new treatment strategies for Parkinson's disease (PD).
      Similar non-human primate models have been developed for translational research
      purposes as large animal models are required by regulatory bodies as an
      intermediate "phase 0" trial step. However, experimental research in non-human
      primates encounters several economical and regulatory issues, which may be
      avoided by the alternative use of pigs as a large animal model for experimental
      brain research. OBJECTIVE: The primary aim of this study was to examine if
      unilateral injections of 6-OHDA into the Gottingen minipig nigrostriatal pathway
      would lead to dopaminergic imbalance and rotational behavior similar to the 6
      OHDA unilateral symptomatic model of PD created in other species. The secondary
      aim was to attempt to verify the rotational behavior as a parkinsonian symptom
      using subthalamic deep brain stimulation (STN-DBS) to minimize the elicited
      rotational pattern. MATERIALS AND METHODS: Using an MRI-based stereotactic
      procedure, ten female Gottingen minipigs were injected unilaterally with 6-OHDA
      in the nigrostriatal pathway. Postoperatively, an MRI was performed, and the
      animals were injected with amphetamine and apomorphine and observed for
      rotational behavior. After a survival period of three months the brains were
      removed and immunohistochemically stained for tyrosine hydroxylase (TH). One week
      before sacrifice two animals had DBS electrodes unilaterally implanted in the
      subthalamic nucleus and various stimulation protocols were conducted during
      amphetamine challenge. RESULTS: As expected most animals rotated towards the side
      of the lesion when given amphetamine (3.5-4.0 mg/kg), whereas the predicted
      opposite response to apomorphine were much harder to reproduce. T1- and T2
      weighted postoperative MRI could demonstrate the size and the location of the 6
      OHDA injection. Postmortem TH-staining of the final two animals receiving a
      medial and a lateral injection of 25 MUL of 6-OHDA (8 MUg/MUL, injection rate 5
      MUL/min) into the diencephalic nigrostriatal pathway showed a prominent
      unilateral decrease in TH-staining of the substantia nigra pars compacta, the
      ventral tegmental area and the nigrostriatal pathway on the lesioned side. These
      two animals displayed spontaneous rotational behavior toward the lesioned side
      for the first 2-3 days postoperatively, and this behavior could later on be
      reelicited by amphetamine and attenuated by ipsilateral STN-DBS. CONCLUSION:
      Female Gottingen minipigs are susceptible to unilateral dopaminergic degeneration
      when properly injected unilaterally with sufficient amounts of 6-OHDA in the
      nigrostriatal pathway. The location of the 6-OHDA injections and thus the
      accuracy of the employed stereotaxy can be verified in vivo using MRI
      postoperatively. The injected minipigs display unilateral parkinsonism with a
      well-defined rotational response to amphetamine that may be ameliated by STN-DBS
      performed on the lesioned side. The response to apomorphine was, however, not
      consistent, illustrating that further work on this promising non-primate large
      animal model is needed, before it is fully similar to the established 6-OHDA
      models in other species.

PMID- 29462644
TI  - Hepatic and cardiac hemodynamics and systemic inflammation in cirrhosis: It takes
      three to tango.

PMID- 29462645
TI  - Reply to: "Antiviral therapy improves survival in patients with HBV infection and
      intrahepatic cholangiocarcinoma undergoing liver resection: Novel concerns".

PMID- 29462646
TI  - CBX3 promotes tumor proliferation by regulating G1/S phase via p21 downregulation
      and associates with poor prognosis in tongue squamous cell carcinoma.
AB  - Chromobox protein homolog 3 (CBX3), a core component of the heterochromatin
      proteins 1, is recently proved to be involved in human cancerogenesis and
      associated with the prognosis of patient. However, the role of CBX3 in Tongue
      squamous cell carcinoma (TSCC) remains unclear. In the present study we found
      that CBX3 was upregulated in TSCC tissues when compared to adjacent non-tumor
      tissues, and multivariable analysis showed that high CBX3 expression was
      associated with clinical stage and cervical node metastasis, which was an
      independent prognostic indicator of TSCC. Furthermore, Kaplan-Meier survival
      analysis and log-rank test showed that TSCC patients with high CBX3 expression
      had a poorer rate of OS compared to patients with low CBX3 expression. Moreover,
      knocking down CBX3 inhibited TSCC cells proliferation both in vitro and in vivo,
      while overexpressing CBX3 promoted TSCC cells proliferation. In addition, CBX3
      depletion resulted in cell cycle delay at the G1/S phase via the p21 pathway. In
      summary, we identifies CBX3 as a potential novel oncogene in TSCC, which may act
      as a biomarker and target in the diagnosis and treatment of this killer disease.

PMID- 29462648
TI  - Bovine viral diarrhea virus type 1 current taxonomy according to palindromic
      nucleotide substitutions method.
AB  - Pestivirus bovine viral diarrhea virus type 1 species is responsible for
      cosmopolitan diseases affecting cattle and other ruminants, presenting a wide
      range of clinical manifestations, with relevant impact on zootechnic production.
      Understanding genomic characteristic and virus taxonomy is fundamental in order
      to sustain control and prophylactic programs. Given the recent various studies
      reporting a relatively high number of new strains, in particular from Asian
      countries, in the present study, four hundred-eighty-two genomic sequences have
      been evaluated applying the palindromic nucleotide substitutions method for
      genotyping. Based on the secondary structure alignment and computing genetic
      distance among strains in the 5' untranslated region of Pestivirus RNA, the
      current taxonomy of the species was reviewed. Twenty-two genotypes have been
      identified, applying a nomenclature based on divergence in the genus.

PMID- 29462647
TI  - Novel pathogenic RECQL4 variants in Chinese patients with Rothmund-Thomson
      syndrome.
AB  - BACKGROUND: Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive
      disorder mainly characterized by cutaneous poikiloderma, sparse hair, short
      stature and skeletal defects. Deleterious mutations in the RecQ-like DNA helicase
      type 4 (RECQL4) gene have been detected in approximately two-thirds of RTS cases.
      METHODS: Three Chinese patients from two unrelated families were enrolled for
      clinical evaluation. Targeted next-generation sequencing (NGS) using a custom
      panel consisting of 705 short-stature-related genes was performed for the
      probands. Variants detected by NGS were confirmed by Sanger sequencing and
      examined in family members. RESULTS: The probands presented with characteristic
      features of severe growth delay, poikiloderma mostly on the face, buttocks and
      extremities, sparse or absent hair, eyelashes, and eyebrows, forearm reduction
      defects, small hands with hypoplasia of the middle phalanx (little finger) in one
      of the probands, epicanthus, hypertelorism, and dental abnormalities. In
      addition, novel auricle features and other rare facial features, including narrow
      palpebral fissure, depressed nasal bridge, and small chin were exhibited. Four
      novel RECQL4 variants were identified, including three pathogenic frameshift
      variants, c.1724_1725delAC, p.His575fs*7; c.2421dupT, p.Asp808*; c.1770_1807del,
      p.Pro591fs*2, and one likely pathogenic missense variant, c.691G>A, p.Gly231Ser.
      CONCLUSION: Our study expands the mutational spectrum of RECQL4 gene and reveals
      novel phenotypes observed in Chinese RTS patients.

PMID- 29462649
TI  - The roles of the analogy with natural selection in B.F. Skinner's philosophy.
AB  - Beginning in the 1950s, B.F. Skinner made increasing reference to an analogy
      between operant conditioning and natural selection. This analogy is the basis of
      an argument that, in contrast to Skinner's other critiques of cognitive science,
      is neither epistemological nor pragmatic. Instead, it is based on the claim that
      ontogenetic adaptation is due to a special mode of causation he called "selection
      by consequences." He argued that this mode of causation conflicts with
      explanations that attribute action to an autonomous agent with reasons for
      acting. This argument dismisses ordinary explanations of action, and has
      implications not only for cognitive science but also for morals. Skinner cited
      the latter implications to counter objections to the application of behavior
      analysis to the reform of society and its institutions. Skinner's critique,
      however, rests upon empirical assumptions that have been criticized by other
      behavior analysts. Although for Skinner the major role of the analogy was to
      propose an empirical thesis, it also can play a metaphysical role-namely, to
      demonstrate the possibility of ontogenetic adaptation without reference to agents
      who have reasons for acting. These two roles, empirical and metaphysical, are the
      mirror image of the empirical and metaphysical roles of the computer analogy for
      cognitive science. That analogy also can be (and has been) interpreted as an
      empirical thesis. Its empirical implications, however, have been difficult to
      confirm. It also, however, has played a metaphysical role-namely, to demonstrate
      the possibility that a physical process could perform logical operations on
      states having propositional content. Neither analogy provides a well-confirmed,
      general answer to the question of how to explain the process of ontogenetic
      adaptation. But together they show there are two metaphysically coherent, but
      conflicting, answers to this question. Depending upon one's epistemology, the
      analogy with natural selection may provide a useful point of departure for a
      strategy of research. Such a pragmatic grounding for a research strategy does
      not, however, provide sufficient reason to abandon for purposes of ethics the
      concept of persons as autonomous agents.

PMID- 29462650
TI  - Song ontogeny in Nuttall's white-crowned sparrows tutored with individual
      phrases.
AB  - Behavioral ontogeny involves the interaction of innate predispositions and
      experience. In bird song learning, one approach to exploring this interaction is
      to examine the songs rehearsed by young birds whose exposure to tutor models has
      been carefully controlled. Here, I analyzed the rehearsed repertoire in Nuttall's
      white-crowned sparrows (Zonotrichia leucophrys nuttalli) tutored with individual
      phrases of conspecific and heterospecific songs. The proportions of phrase types
      rehearsed indicate that the learning biases evident in crystallized song are
      manifest early on, suggesting preferential memorization rather than preferential
      retention during attrition. The proportion of songs beginning with whistles
      increased during song rehearsal and phrase sequence variability decreased,
      consistent with the idea that innate syntax specifications guide song rehearsal.
      Single-phrase tutored birds overproduced phrases to the same extent previously
      observed in birds tutored with full, normal song but retained fewer phrase types
      in their crystallized repertoires. This suggests that in this subspecies,
      acquired syntax information does not affect the number of phrase types memorized
      and rehearsed but does affect repertoire attrition at the end of the sensorimotor
      phase. I discuss these results with a focus on the action of innate templates in
      song development and subspecies differences in this process.

PMID- 29462651
TI  - No subchronic toxicity of multiple herbicide-resistant soybean FG72 in Sprague
      Dawley rats by 90-days feeding study.
AB  - The genetically modified (GM) soybean FG72 contains two exogenous genes: p
      hydroxyphenylpyruvate dioxygenase (hppd) and double mutant 5-enol
      pyruvylshikimate-3-phosphate synthase (2mepsps), endowing the FG72 with the
      glyphosate and isoxaflutole herbicides resistant abilities for presence of the
      2mEPSPS and HPPD W336 proteins. A food safety assessment of GM soybean FG72 was
      evaluated by a 90-days feeding study using three different dietary concentrations
      (7.5%, 15%, or 30% w/w) of the GM soybean or its corresponding non-GM cultivar
      Jack fed to Sprague-Dawley rats. In our study, no biologically significant
      differences on animal daily clinical signs, body weights, clinical observations,
      hematology, clinical chemistry, histopathology on selected organs were observed
      within the GM soybean groups and among the GM soybean groups, the non-GM soybean
      groups and the control group. The results of the 90-days subchronic feeding study
      demonstrated that the GM soybean FG72 is as safe as the conventional non-GM
      soybean Jack.

PMID- 29462652
TI  - The role of intraamygdaloid neurotensin and dopamine interaction in conditioned
      place preference.
AB  - Tridecapeptide Neurotensin (NT) is widely distributed in the central nervous
      system where it acts as a neurotransmitter and neuromodulator. The central
      nucleus of amygdala (CeA), part of the limbic system, plays an important role in
      learning, memory, anxiety and reinforcing mechanisms. Our previous data showed
      that NT microinjected into the CeA has positive reinforcing properties. We
      supposed that these effects might be due to modulations of the mesolimbic
      dopamine system. The aim of our study was to examine in the CeA the possible
      effects of NT and dopamine interaction on reinforcement by conditioned place
      preference test. Male Wistar rats were microinjected bilaterally with 100 ng NT
      or 2 MUg D1 dopamine receptor antagonist alone, or D1 dopamine antagonist 15 min
      before 100 ng NT treatment or vehicle solution into the CeA. Other animals
      received 4 MUg D2 dopamine receptor antagonist Sulpiride alone, or administration
      of D2 dopamine receptor antagonist 15 min before 100 ng NT treatment or vehicle
      solution into the CeA. Rats that received 100 ng NT spent significantly more time
      in the treatment quadrant during the test session. Pre-treatment with the D1
      dopamine antagonist, blocked the effects of NT. D2 dopamine receptor antagonist
      pretreatment could prevent the positive reinforcing effects of NT as well.
      Antagonists themselves did not influence the place preference. Our results show
      that the rewarding effect of NT can be due to the modulation of DA system, since
      its effects could be blocked by either D1 dopamine or D2 dopamine antagonist
      preteatment.

PMID- 29462654
TI  - Neighbourhoods and obesity: A prospective study of characteristics of the built
      environment and their association with adiposity outcomes in children in
      Montreal, Canada.
AB  - This paper examined prospective associations between built environment features
      assessed at baseline using direct audits and adiposity outcomes two years later
      in Montreal, Canada. Data stem from the Quebec Adipose and Lifestyle
      Investigation in Youth study of 630 children aged 8-10 years with a parental
      history of obesity. Baseline measurements took place between 2005 and 2008.
      Follow-up took place between 2008 and 2011. Built environment features were
      assessed at baseline in up to 10 contiguous street segments around participants'
      residential addresses using on-site audits. Analyses were restricted to
      participants who reported the same address both at baseline and follow-up.
      Prospective associations between adiposity outcomes at follow-up (BMI z-score and
      waist-height ratio) and built environment features at baseline (traffic-calming
      features, pedestrian aids, disorder, physical activity facilities, convenience
      stores, and fast-food restaurants) were examined using multivariable regression
      models. 391 children were included in the analyses. In fully-adjusted models,
      children living in residential areas with presence of pedestrian aids had lower
      BMI z-score, and lower waist-height ratio. Also, children residing in residential
      areas with at least one convenience store had lower BMI z-score, and lower waist
      height ratio at follow-up. Findings provide evidence of the potential role of
      street-level urban design features in shaping childhood adiposity. To better
      inform policy and intervention, future research should explore the possibility of
      reducing obesogenic neighbourhoods by enhancing street-level design features.

PMID- 29462655
TI  - Convergence of BOLD and ERP measures of neural reactivity to emotional faces in
      children and adolescents with and without anxiety disorders.
AB  - The neural bases of emotion are commonly measured using blood-oxygen-level
      dependent (BOLD) signal and the late positive potential (LPP) event-related
      potential (ERP) component, but rarely together in the same individuals. Despite
      evidence of developmental changes in processing socio-emotional signals (e.g.,
      faces) as reflected by both BOLD and LPP indices of brain maturation, the
      literature on the correspondence between these measures is limited to healthy
      adults, leaving questions regarding such correspondence across development and in
      clinical populations unaddressed. We examined the relationship between BOLD and
      LPP during an emotional face processing task in a large sample of youth (N = 70;
      age 7-19 years) with and without anxiety disorders, and tested whether BOLD
      signal in regions corresponding to LPP may account for age-related decreases in
      LPP. Greater activation in bilateral inferior frontal gyrus (IFG)/orbitofrontal
      gyrus (OFG), left supplementary motor area, right superior parietal lobule, and
      bilateral amygdala correlated with enhanced LPP to emotional faces in both
      anxious and healthy youth. Older youth exhibited reduced activation in bilateral
      IFG/OFG and bilateral amygdala, as well as reduced LPP. Decreased right IFG/OFG
      activation mediated the association between age and LPP. These findings support
      correspondence between these measures and need for multi-method approaches and
      indicate that age-related decreases in LPP may be driven, in part, by decreased
      IFG/OFG activation.

PMID- 29462656
TI  - EEG phase states at stimulus onset in a variable-ISI Go/NoGo task: Effects on ERP
      components.
AB  - Previous EEG-ERP dynamics studies found non-random "preferred" EEG phases at
      stimulus onset in a fixed interstimulus interval (ISI) equiprobable auditory
      Go/NoGo paradigm, with substantial effects on ERP components. Here we changed to
      a variable ISI task to prevent/reduce preferential phase occurrence. Discrete
      Fourier transforms decomposed prestimulus EEG at Cz for each trial to calculate
      the phase of different frequencies at stimulus onset; we combined these into the
      delta, theta, alpha, and beta bands, and then sorted trials into phase quartiles
      for each. ERPs from the raw EEG, assessed using temporal Principal Components
      Analyses, were examined as a function of phase at stimulus onset. Preferential
      phase occurrence was reduced as predicted, but random phase substantially
      impacted component amplitudes. For example, negativity in delta enhanced Go and
      NoGo P3b; and in theta reduced NoGo but not Go P3b. Overall, EEG phases at
      stimulus onset support differential cognitive processing in this two-choice task.

PMID- 29462653
TI  - Neuroinflammation in Alzheimer's disease: Pleiotropic roles for cytokines and
      neuronal pentraxins.
AB  - Neuroinflammation is a potential factor speculated to underlie Alzheimer's
      disease (AD) etiopathogenesis and progression. The overwhelming focus in this
      area of research to date has been on the chronic upregulation of pro-inflammatory
      cytokines to understand how neuroinflammatory mechanisms contribute to
      neurodegeneration. Yet, it is important to understand the pleiotropic roles of
      these cytokines in modulating neuroinflammation in which they cannot be labeled
      as a strictly "good" or "bad" biomarker phenotype. As such, biomarkers with more
      precise functions are needed to better understand how neuroinflammation impacts
      the brain in AD. Neuronal pentraxins are a concentration- dependent group of pro-
      or anti- inflammatory cytokines. There is contradictory evidence of these
      pentraxins as being both neuroprotective and potentially detrimental in AD.
      Potential neuroprotective examples include their ability to predict AD-related
      outcomes such as cognition, memory function and synaptic refinement. This review
      will briefly outline the basis of AD and subsequently summarize findings for
      neuropathological mechanisms of neuroinflammation, roles for traditional pro-and
      anti-inflammatory cytokines, and data found thus far on the neuronal pentraxins.

PMID- 29462657
TI  - Serlopitant for the treatment of chronic pruritus: Results of a randomized,
      multicenter, placebo-controlled phase 2 clinical trial.
AB  - BACKGROUND: The substance P/neurokinin 1 receptor pathway is critical in chronic
      pruritus; anecdotal evidence suggests that antagonism of this pathway can reduce
      chronic itch. OBJECTIVE: To assess the safety and efficacy of the substance
      P/neurokinin 1 receptor antagonist serlopitant in treating chronic pruritus.
      METHODS: Eligible patients with severe chronic pruritus who were refractory to
      antihistamines or topical steroids were randomized to serlopitant, 0.25, 1, or 5
      mg, or to placebo, administered once daily for 6 weeks as monotherapy or with
      midpotency steroids and emollients. The primary efficacy end point was percentage
      change in visual analog scale pruritus score from baseline. RESULTS: Serlopitant
      treatment resulted in a dose-dependent decrease in pruritus. The mean percentage
      decreases from baseline visual analog scale pruritus scores were statistically
      significantly larger with the 1- and 5-mg doses of serlopitant (P = .022 and P =
      .013, respectively) than with placebo at week 6. No significant safety or
      tolerability differences were detected among the groups. LIMITATIONS: The sample
      size was insufficient for subgroup analyses of the efficacy of serlopitant for
      chronic pruritus on the basis of underlying conditions. CONCLUSIONS: Serlopitant,
      1 mg and 5 mg daily, was associated with a statistically significant reduction in
      chronic pruritus and was well tolerated (NCT01951274).

PMID- 29462658
TI  - Affinity-based separation methods for the study of biological interactions: The
      case of peroxisome proliferator-activated receptors in drug discovery.
AB  - Affinity-based methods using immobilized proteins are important approaches for
      understanding the interactions between small molecules and biological targets.
      This review is intended to provide an overview of different affinity based
      separation methods that have been applied to the study of peroxisome proliferator
      activated receptors (PPARs). The screening of compound to increase screening
      rates for synthetic and natural ligands of PPAR are reported. Pros and cons of
      the approaches in ligand discovery initiatives are discussed.

PMID- 29462659
TI  - Safer approaches to therapeutic modulation of TGF-beta signaling for respiratory
      disease.
AB  - The transforming growth factor (TGF)-beta cytokines play a central role in
      development and progression of chronic respiratory diseases. TGF-beta
      overexpression in chronic inflammation, remodeling, fibrotic process and
      susceptibility to viral infection is established in the most prevalent chronic
      respiratory diseases including asthma, COPD, lung cancer and idiopathic pulmonary
      fibrosis. Despite the overwhelming burden of respiratory diseases in the world,
      new pharmacological therapies have been limited in impact. Although TGF-beta
      inhibition as a therapeutic strategy carries great expectations, the constraints
      in avoiding compromising the beneficial pleiotropic effects of TGF-beta,
      including the anti-proliferative and immune suppressive effects, have limited the
      development of effective pharmacological modulators. In this review, we focus on
      the pathways subserving deleterious and beneficial TGF-beta effects to identify
      strategies for selective modulation of more distal signaling pathways that may
      result in agents with improved safety/efficacy profiles. Adverse effects of TGF
      beta inhibitors in respiratory clinical trials are comprehensively reviewed,
      including those of the marketed TGF-beta modulators, pirfenidone and nintedanib.
      Precise modulation of TGF-beta signaling may result in new safer therapies for
      chronic respiratory diseases.

PMID- 29462660
TI  - Evaluation of the medical devices benchmark materials in the controlled human
      patch testing and in the RhE in vitro skin irritation protocol.
AB  - Several irritants were used in the in vitro irritation medical device round
      robin. The objective of this study was to verify their irritation potential using
      the human patch test (HPT), an in vitro assay, and in vivo data. The irritants
      were lactic acid (LA), heptanoic acid (HA), sodium dodecyl sulfate (SDS),
      Genapol(r) X-80 (GP), and Y-4 polymer. Dilute saline and sesame seed oil (SSO)
      solutions of each were evaluated using a 4 and 18 h HPT and the EpiDermTM SIT-MD
      RhE assay; results were then compared to existing rabbit skin irritation test
      data. Results from the 4 h HPT were negative in most cases except for GP and SDS,
      while the 18 h HPT also identified some LA, HA, and GP samples as irritants.
      EpiDermTM SIT-MD correctly identified all irritants except GP in SSO due to
      limited solubility. Data from cutaneous rabbit irritation tests were negative,
      while all intracutaneous results were strongly or weakly positive except for the
      most dilute GP solutions. These findings indicate that EpiDermTM SIT-MD results
      correlate with those from the rabbit intracutaneous test and confirm that RhE
      assays are suitable replacements for animals in evaluating the tissue irritation
      potential of medical devices.

PMID- 29462662
TI  - A balanced ATP driving force module for enhancing photosynthetic biosynthesis of
      3-hydroxybutyrate from CO2.
AB  - Using engineered photoautotrophic microorganisms for the direct chemical
      synthesis from CO2 is an attractive direction for both sustainability and CO2
      mitigation. However, the behaviors of non-native metabolic pathways may be
      difficult to control due to the different intracellular contexts between natural
      and heterologous hosts. While most metabolic engineering efforts focus on
      strengthening driving forces in pathway design to favor biochemical production in
      these organisms, excessive driving force may be detrimental to product
      biosynthesis due to imbalanced cellular intermediate distribution. In this study,
      an ATP-hydrolysis based driving force module was engineered into cyanobacterium
      Synechococcus elongatus PCC 7942 to produce 3-hydroxybutyrate (3HB), a valuable
      chemical feedstock for the synthesis of biodegradable plastics and antibiotics.
      However, while the ATP driving force module is effective for increasing product
      formation, uncontrolled accumulation of intermediate metabolites likely led to
      metabolic imbalance and thus to cell growth inhibition. Therefore, the ATP
      driving force module was reengineered by providing a reversible outlet for
      excessive carbon flux. Upon expression of this balanced ATP driving force module
      with 3HB biosynthesis, engineered strain produced 3HB with a cumulative titer of
      1.2 g/L, a significant increase over the initial strain. This result highlighted
      the importance of pathway reversibility as an effective design strategy for
      balancing driving force and intermediate accumulation, thereby achieving a self
      regulated control for increased net flux towards product biosynthesis.

PMID- 29462661
TI  - p66Shc regulates migration of castration-resistant prostate cancer cells.
AB  - Metastatic castration-resistant (CR) prostate cancer (PCa) is a lethal disease
      for which no effective treatment is currently available. p66Shc is an oxidase
      previously shown to promote androgen-independent cell growth through generation
      of reactive oxygen species (ROS) and is elevated in clinical PCa and multiple CR
      PCa cell lines. We hypothesize p66Shc also increases the migratory activity of
      PCa cells through ROS and investigate the associated mechanism. Using the
      transwell assay, our study reveals that the level of p66Shc protein correlates
      with cell migratory ability across several PCa cell lines. Furthermore, we show
      hydrogen peroxide treatment induces migration of PCa cells that express low
      levels of p66Shc in a dose-dependent manner, while antioxidants inhibit
      migration. Conversely, PCa cells that express high levels of endogenous p66Shc or
      by cDNA transfection possess increased cell migration which is mitigated upon
      p66Shc shRNA transfection or expression of oxidase-deficient dominant-negative
      p66Shc W134F mutant. Protein microarray and immunoblot analyses reveal multiple
      proteins, including ErbB-2, AKT, mTOR, ERK, FOXM1, PYK2 and Rac1, are activated
      in p66Shc-elevated cells. Their involvement in PCa migration was examined using
      respective small-molecule inhibitors. The role of Rac1 was further validated
      using cDNA transfection and, significantly, p66Shc is found to promote
      lamellipodia formation through Rac1 activation. In summary, the results of our
      current studies clearly indicate p66Shc also regulates PCa cell migration through
      ROS-mediated activation of migration-associated proteins, notably Rac1.

PMID- 29462663
TI  - Zinc phthalocyanine encapsulated in polymer micelles as a potent photosensitizer
      for the photodynamic therapy of osteosarcoma.
AB  - Zinc phthalocyanine (ZnPc) is a highly potent second-generation photosensitizer
      for cancer photodynamic therapy (PDT) with attractive photo-physical and photo
      chemical properties. However, poor solubility and strong trend of crystallization
      prevent it from loading in most of drug delivery systems and hamper its further
      application. Herein, to overcome this problem, an amphiphilic block copolymer
      poly(ethylene glycol)-poly[2-(methylacryloyl)ethylnicotinate] (PEG-PMAN) with
      aromatic nicotinate is used to load ZnPc for their pi-pi interactions. The formed
      PEG-PMAN/ZnPc nanoparticle (PPZ) dramatically increases reactive oxygen species
      production in osteosarcoma cells after light irradiation, causes mitochondrial
      injury and promotes cell cycle arrest at G2/M, leading to a 100-fold cytotoxicity
      improvement comparing with free ZnPc. The excellent therapeutic effectiveness and
      safety of PPZ are also proved by in vivo experiments operating on osteosarcoma
      model. The finding above indicates that PPZ has promising clinical applications
      as a next-generation photosensitizer in PDT of osteosarcoma.

PMID- 29462664
TI  - Global proteomic and functional analysis of Crotalus durissus collilineatus
      individual venom variation and its impact on envenoming.
AB  - : Individual variations studies are important to understand the snakebite
      envenoming and to improve the antivenom production and its effectiveness. In this
      way, the objective of this study was a comparative analysis of intraspecific
      variation in the venom composition of 22 Crotalus durissus collilineatus
      specimens through proteomic techniques. Venoms were fractionated by RP-FPLC, and
      analyzed by SDS-PAGE and mass spectrometry. Although similar, chromatographic and
      electrophoretic profiles showed significant qualitative and quantitative
      differences. Some venom components were identified for the very first time in C.
      d. collilineatus, such as glutathione peroxidase, nerve growth factor, 5'
      nucleotidase, angiotensin-converting enzyme, carboxypeptidase, phosphodiesterase,
      glutaminyl cyclase and phospholipase B. Regarding hyaluronidase activity, 2
      venoms did not present detectable enzyme activity in the tested amounts.
      Additionally, in vivo crotalic envenoming in mice showed that venoms from
      different specimens resulted in diversified changes of biochemical and
      immunological parameters, such as creatine kinase and interleukin 6. This study
      demonstrated significant intraspecific variations in the venom of C. d.
      collilineatus, which may impact the production and effectiveness of the antivenom
      therapy. BIOLOGICAL SIGNIFICANCE: This study performed the proteomic and
      functional analyzes of 22 C. d. collilineatus individual venoms and verified the
      occurrence of quali and quantitative variations among them. The venoms evaluated
      caused envenomings with different changes in biochemical and immunological
      parameters. These results confirm the need to use a pool of venoms with the
      greatest possible variability in the preparation of antivenoms, in order to
      improve their effectiveness. In addition, this study was able to identify for the
      first time 8 different proteins in this subspecies venom, increasing knowledge
      about its composition and showing that it is a source of these proteins with
      possible biotechnological applications.

PMID- 29462665
TI  - Cognitive assessment in patients with multiple sclerosis: From neuropsychological
      batteries to ecological tools.
AB  - BACKGROUND: Cognitive impairment (CI) is frequent in patients with multiple
      sclerosis (PwMS) and could negatively affect family social and vocational
      activities. Detecting CI is clinically relevant, so the emerging question is the
      strategy for assessing cognition in MS. OBJECTIVE: An update on cognitive
      assessment in PwMS with use of standard neuropsychological (NP) tests and
      ecological tools. RESULTS: The minimal cognitive assessment in MS should include
      at least NP tests assessing information processing speed (IPS) and verbal and
      visuospatial episodic memory. The IPS could be easily and quickly evaluated with
      symbol digit substitution tests by using paper for the oral version of the Symbol
      Digit Modalities Test or a laptop for the Computerised Speed Cognitive Test. The
      comprehensive NP battery must be performed by a qualified neuropsychologist to
      adequately characterize the extent and severity of CI in PwMS. The quiet and
      controlled environment used for this standardized assessment could be a
      limitation for generalizing the results because it does not reflect real daily
      life conditions. Thus, this context could decrease the ability to detect some
      cognitive deficits that could occur only in more complex situations. Thus,
      ecological evaluation seems a complementary and promising approach for detecting
      cognitive abnormalities in daily activities. CONCLUSION: Recent efforts have been
      made to detect and characterize cognitive deficits in PwMS. Some IPS and episodic
      memory NP tests have been validated in MS and should be proposed to patients in
      the clinical setting. Besides NP tests, ecological tools are becoming important
      for detecting cognitive dysfunction in everyday-like conditions. Further research
      is needed to validate relevant tools for monitoring cognition in MS and the
      ability to detect clinically meaningful change in longitudinal studies.

PMID- 29462666
TI  - Spinocerebellar Ataxia Tethering PCR: A Rapid Genetic Test for the Diagnosis of
      Spinocerebellar Ataxia Types 1, 2, 3, 6, and 7 by PCR and Capillary
      Electrophoresis.
AB  - Spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7, associated with a (CAG)n
      repeat expansion in coding sequences, are the most prevalent autosomal dominant
      ataxias worldwide (approximately 60% of the cases). In addition, the phenotype of
      SCA2 expansions has been now extended to Parkinson disease and amyotrophic
      lateral sclerosis. Their diagnosis is currently based on a PCR to identify small
      expanded alleles, followed by a second-level test whenever a false normal
      homozygous or a CAT interruption in SCA1 needs to be verified. Next-generation
      sequencing still does not allow efficient detection of these repeats. Here, we
      show the efficacy of a novel, rapid, and cost-effective method to identify and
      size pathogenic expansions in SCA1, 2, 3, 6, and 7 and recognize large alleles or
      interruptions without a second-level test. Twenty-five healthy controls and 33
      expansion carriers were analyzed: alleles migrated consistently in different PCRs
      and capillary runs, and homozygous individuals were always distinguishable from
      heterozygous carriers of both common and large (>100 repeats) pathogenic CAG
      expansions. Repeat number could be calculated counting the number of peaks,
      except for the largest SCA2 and SCA7 alleles. Interruptions in SCA1 were always
      visible. Overall, our method allows a simpler, cost-effective, and sensibly
      faster SCA diagnostic protocol compared with the standard technique and to the
      still unadapted next-generation sequencing.

PMID- 29462667
TI  - A Proximity Extension Assay (PEA)-based method for quantification of bevacizumab.
AB  - INTRODUCTION: Proximity Extension Assay (PEA) is a direct one-step protein
      quantification method using a pair of DNA oligonucleotides linked to antibodies
      against the target molecule. It requires polyclonal or two monoclonal antibodies
      (mAbs) that bind to target epitopes close enough to form a DNA duplex which is
      quantified by real-time PCR. Bevacizumab, an anti-cancer drug, is a mAb against
      vascular endothelial growth factor with common cardiovascular adverse effects. It
      is widely used off-label to treat neovascular eye disorders by intravitreal
      application of small doses. Even then, certain amount reaches systemic
      circulation which is considered relevant regarding safety. We aimed to set-up a
      PEA-based assay for bevacizumab in human plasma and to preliminary evaluate it in
      patients treated intravitreally. METHODS: We tested (PEA, quantitative PCR)
      several combinations of commercial mAbs and a Fab fragment against bevacizumab.
      The best combination was used to quantify bevacizumab in three patients donating
      plasma before and 24 h after the first intravitreal injection. RESULTS: A
      combination of a mAb and a Fab fragment (HCA184 and HCA182, Bio-Rad Laboratories,
      Inc.) performed best: standard curve R2 0.98, linear dynamic range 1-1000 pM,
      lower limit of quantification 1 pM (149 pg/mL) and a satisfactory precision
      (coefficient of variation 12%). All pre-dose patient concentrations were zero,
      while post-dose concentrations were 10.94, 13.73 and 55.49 ng/mL, in line with
      previous reports. DISCUSSION: This is the first set-up of a PEA-based assay for
      quantification of bevacizumab in human plasma. Its good performance and high
      sensitivity support further evaluation for potential uses particularly when the
      expected concentrations are low.

PMID- 29462668
TI  - Mismatches between major subhierarchies and semantic tags in SNOMED CT.
AB  - The fully specified name of a concept in SNOMED CT is formed by a term to which
      in the typical case is added a semantic tag. The latter is meant to disambiguate
      homonymous terms and to indicate in which major subhierarchy of SNOMED CT that
      concept fits. We have developed a method to determine whether a concept's tag
      correctly identifies its place in the hierarchy, and applied this method to an
      analysis of all active concepts in every SNOMED CT release from January 2003 to
      January 2017. Our results show (1) that there are concepts in almost every
      release whose semantic tag does not match their placement in the hierarchy, (2)
      that it is primarily disorder concepts that are involved, and (3) that the number
      of such mismatches increase since the July 2012 version. Our analysis determined
      that it is primarily the absence of a mechanism in the SNOMED CT authoring
      environment to suggest stated relationships for very similar concepts that is
      responsible for the mismatches. We argue that the SNOMED CT authoring environment
      should treat the semantic tags as part of the formal structure so that methods
      can be implemented to keep the sub-hierarchies in sync with the semantic tags.

PMID- 29462669
TI  - Assessing the practice of biomedical ontology evaluation: Gaps and opportunities.
AB  - With the proliferation of heterogeneous health care data in the last three
      decades, biomedical ontologies and controlled biomedical terminologies play a
      more and more important role in knowledge representation and management, data
      integration, natural language processing, as well as decision support for health
      information systems and biomedical research. Biomedical ontologies and controlled
      terminologies are intended to assure interoperability. Nevertheless, the quality
      of biomedical ontologies has hindered their applicability and subsequent adoption
      in real-world applications. Ontology evaluation is an integral part of ontology
      development and maintenance. In the biomedicine domain, ontology evaluation is
      often conducted by third parties as a quality assurance (or auditing) effort that
      focuses on identifying modeling errors and inconsistencies. In this work, we
      first organized four categorical schemes of ontology evaluation methods in the
      existing literature to create an integrated taxonomy. Further, to understand the
      ontology evaluation practice in the biomedicine domain, we reviewed a sample of
      200 ontologies from the National Center for Biomedical Ontology (NCBO) BioPortal
      the largest repository for biomedical ontologies-and observed that only 15 of
      these ontologies have documented evaluation in their corresponding inception
      papers. We then surveyed the recent quality assurance approaches for biomedical
      ontologies and their use. We also mapped these quality assurance approaches to
      the ontology evaluation criteria. It is our anticipation that ontology evaluation
      and quality assurance approaches will be more widely adopted in the development
      life cycle of biomedical ontologies.

PMID- 29462671
TI  - Expression of the adhesion G protein-coupled receptor A2 (adgra2) during Xenopus
      laevis development.
AB  - The adhesion G protein-coupled receptor A2 (Adgra2) is a seven transmembrane
      receptor that has been described to be a regulator for angiogenesis in mice.
      Furthermore, the zebrafish ouchless mutant is unable to develop dorsal root
      ganglia through a disrupted trafficking of Adgra2. Besides RNA sequencing data,
      nothing is reported about Adgra2 in the south African crawled frog Xenopus
      laevis. In this study, we investigated for the first time the spatio-temporal
      expression of adgra2 during early Xenopus embryogenesis in detail. In silico
      approaches showed that the genomic adgra2 region as well as the Adgra2 protein
      sequence is highly conserved among different species including Xenopus. RT-PCR
      experiments confirmed that embryonic adgra2 expression is primarily detected at
      the beginning of neurulation and is then present throughout the whole Xenopus
      embryogenesis until stage 42. Whole mount in situ hybridization approaches
      visualized adgra2 expression in many tissues during Xenopus embryogenesis such as
      the cardiovascular system including the heart, the migrating neural crest cells
      and the developing eye including the periocular mesenchyme. Our results indicate
      a role of Adgra2 for embryogenesis and are a good starting point for further
      functional studies during early vertebrate development.

PMID- 29462672
TI  - Use of high-dose intermittent systemic glucocorticoids and the risk of fracture
      in patients with chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterised by
      persistent airflow obstruction and respiratory symptoms. While short course
      systemic GCs are prescribed in patients with acute COPD exacerbations, little is
      known of the risk of fractures with intermittent exposure to high-dose GC and the
      effect of proxies of disease severity. METHODS: A case-control study was
      conducted using the Danish National Hospital Discharge Registry (NHDR) between
      January 1996 to December 2011. Conditional logistics regression models were used
      to derive adjusted odds ratios (OR) risk of fractures in subjects with COPD
      stratified by intermittent high-dose, and proxies of disease severity. RESULT: A
      total of 635,536 cases and the same number of controls were identified (mean age
      67.5+/-13.8, 65% female). COPD patients with intermittent use of high average
      daily dose oral glucocorticoids did not have an increased risk of any,
      osteoporotic, hip or clinically symptomatic vertebral fracture compared to non
      COPD patients (adj. OR 0.65; 95% CI: 0.50-0.86, 0.70; 95% CI: 0.70-0.99, 1.17;
      95% CI: 0.59-2.32, 1.98; 95% CI: 0.59-6.65 respectively). We identified an
      elevated risk of osteoporotic fracture among patients who visited the emergency
      unit (adj. OR 1.47; 95% CI 1.20-1.79) or were hospitalised in the past year for
      COPD (adj. OR 1.76; 95% CI 1.66-1.85). Current GC use among COPD patients was
      associated with an increased risk of osteoporotic, hip and clinically symptomatic
      vertebral fractures compared to patients without COPD. CONCLUSION: Intermittent
      high-dose GCs was not associated with an increased risk of any, osteoporotic, hip
      or clinically symptomatic vertebral fractures in patients with COPD. Current GC
      use was however associated with an increased risk of hip and clinically
      symptomatic vertebral fractures. Therefore, emphasis on prophylactic treatment of
      fractures may not be essential in patients with COPD receiving intermittent dose
      of GCs, whereas this should be considered for high-dose long-term users with
      advanced COPD disease stage, postmenopausal women and men over 40years.

PMID- 29462670
TI  - Microvesicles as Emerging Biomarkers and Therapeutic Targets in Cardiometabolic
      Diseases.
AB  - Microvesicles (MVs, also known as microparticles) are small vesicles that
      originate from plasma membrane of almost all eukaryotic cells during apoptosis or
      activation. MVs can serve as extracellular vehicles to transport bioactive
      molecules from their parental cells to recipient target cells, thereby serving as
      novel mediators for intercellular communication. Importantly, more and more
      evidence indicates that MVs could play important roles in early pathogenesis and
      subsequent progression of cardiovascular and metabolic diseases. Elevated plasma
      concentrations of MVs, originating from red blood cells, leukocytes, platelets,
      or other organs and tissues, have been reported in various cardiometabolic
      diseases. Circulating MVs could serve as potential biomarkers for disease
      diagnosis or therapeutic monitoring. In this review, we summarized recently
      published studies in the field and discussed the role of MVs in the pathogenesis
      of cardiometabolic diseases. The emerging values of MVs that serve as biomarker
      for non-invasive diagnosis and prognosis, as well as their roles as novel
      therapeutic targets in cardiometabolic diseases, were also described.

PMID- 29462673
TI  - Heterotopic ossification and lessons learned from fifteen years at war: A review
      of therapy, novel research, and future directions for military and civilian
      orthopaedic trauma.
AB  - Heterotopic ossification, the formation of bone in soft tissues, is a common
      complication of the high-energy extremity trauma sustained in modern armed
      conflict. In the past 15years, military treatment facilities and aligned
      laboratories have been in a unique position to study and treat this process due
      to the high volume of patients with these injuries secondary to blast trauma. The
      devastating nature of these wounds has limited traditional therapeutic options,
      necessitating alternative solutions to prophylaxis and initial treatment
      producing substantial advances in modeling, prophylaxis, detection, and therapy.
      Specific developments include establishment of an animal model that reproduces
      the systemic and local tissue injury of blast injuries, the use of molecular
      assays and predictive modeling in clinical decision making, advances in early
      detection including Raman spectroscopy, and investigation of prophylactic and
      therapeutic pharmacotherapy targeting the molecular pathways of aberrant bone
      formation. In this review article, we will present the literature to date,
      ongoing studies, and future directions for investigation of heterotopic
      ossification, with a focus on military-specific research.

PMID- 29462674
TI  - Lysophosphatidic acid in medicinal herbs enhances prostaglandin E2 and protects
      against indomethacin-induced gastric cell damage in vivo and in vitro.
AB  - Lysophosphatidic acid (LPA) is a bioactive phospholipid that induces diverse
      biological responses. Recently, we found that LPA ameliorates NSAIDs-induced
      gastric ulcer in mice. Here, we quantified LPA in 21 medicinal herbs used for
      treatment of gastrointestinal (GI) disorders. We found that half of them
      contained LPA at relatively high levels (40-240 MUg/g) compared to soybean seed
      powder (4.6 MUg/g), which we previously identified as an LPA-rich food. The LPA
      in peony (Paeonia lactiflora) root powder is highly concentrated in the lipid
      fraction that ameliorates indomethacin-induced gastric ulcer in mice. Synthetic
      18:1 LPA, peony root LPA and peony root lipid enhanced prostaglandin E2
      production in a gastric cancer cell line, MKN74 cells that express LPA2
      abundantly. These materials also prevented indomethacin-induced cell death and
      stimulated the proliferation of MKN74 cells. We found that LPA was present in
      stomach fluids at 2.4 MUM, which is an effective LPA concentration for inducing a
      cellular response in vitro. These results indicated that LPA is one of the active
      components of medicinal herbs for the treatment of GI disorder and that orally
      administered LPA-rich herbs may augment the protective actions of endogenous LPA
      on gastric mucosa.

PMID- 29462675
TI  - Spiroides shrubs on Qinghai-Tibetan Plateau: Multilocus phylogeography and
      palaeodistributional reconstruction of Spiraea alpina and S. Mongolica
      (Rosaceae).
AB  - A common hypothesis for the rich biodiversity found in mountains is uplift-driven
      diversification. Using a multilocus approach, here we assessed the influence of
      Qinghai-Tibetan Plateau (QTP) uplift and fluctuating regional climate on genetic
      diversity of two sister spiroides shrubs, Spiraea alpina and S. mongolica.
      Combined with palaeodistributional reconstruction modelling, we investigated the
      current and past-predicted distribution of these species under different climatic
      episodes. The study demonstrated that continuous pulses of retreat and expansion
      during last glacial-interglacial episodes, combined with the uplifting of QTP
      shaped the current distribution of these species. All the populations showed high
      level of genetic diversity based on both cpDNA and SSR markers. The average gene
      diversity within populations based on cpDNA markers was 0.383 +/- 0.052 for S.
      alpina and 0.477 +/- 0.048 for S. mongolica. The observed and expected
      heterozygosities based on SSR for both Spiraea alpina and S. mongolicawere
      HE(0.72-0.90)/HO(0.35-0.78) and HE(0.77-0.92)/HO(0.47-0.77) respectively.
      Palaeodistributional reconstruction indicated species' preferences at
      southeastern edge of the plateau during last glacial maximum, at higher altitude
      areas of QTP and range expansion to central plateau during the interglacial
      episodes. Assignment tests in STRUCTURE, discriminant analysis of principal
      coordinates and Immigrants analysis in GENECLASS based on nuclear SSR markers did
      not support the hypothesis of gene flow between both the species. However,
      maximum likelihood approach based on cpDNA showed sharing of haplotypes between
      both species.

PMID- 29462676
TI  - An autopsy case of nearly complete ossification of the stylohyoid chain: Eagle
      syndrome in forensic aspect.

PMID- 29462677
TI  - Characterization of the complete mitochondrial genome of Biston marginata
      (Lepidoptera: Geometridae) and phylogenetic analysis among lepidopteran insects.
AB  - The complete mitochondrial genome (mitogenome) of Biston marginata (Lepidoptera:
      Geometridae) was determined and annotated. The circular genome is 15,470bp long
      and it contains the entire set of 37 genes usually present in lepidopteran
      mitogenomes. The nucleotide composition of the genome is highly A+T biased,
      accounting for 81.20%, with a slightly positive AT skewness (0.028), indicating
      the occurrence of more As than Ts, as found in other Geometridae species. Except
      for cox1 gene starts with non-canonical initial codon CGA, all protein-coding
      genes start with ATN codon. Three of the 13 PCGs (protein coding gene) had an
      incomplete termination codon, T or TA, while the others terminated with TAA. All
      tRNA genes are predicted to fold into typical clover-leaf secondary structure,
      except for the trnS1 (AGN), in which the dihydrouridine (DHU) arm could not form
      a stable stem-loop structure. The A+T-rich region of 343bp is comprised of non
      repetitive sequences, but have several distinctive features, including the motif
      "ATAGA" followed by a 19bp poly-T stretch, a microsatellite-like (TA)7 element
      next to the ATTTA motif. The phylogenetic analyses support the view that the B.
      marginata is closely related to the Biston pantrinaria, and confirm that Biston
      marginata belongs to the family Geometridae.

PMID- 29462678
TI  - The effect of different substitute groups and molecular weights of fucoidan on
      neuroprotective and anticomplement activity.
AB  - Ten fucoidan (FPS) derivatives were successfully synthesized, and their potential
      neuroprotective and anticomplement activities were investigated employing various
      established in vitro systems. The aim of the present study was to investigate the
      effects of different substitute groups and molecular weights of fucoidan on
      neuroprotective and anticomplement activities. All FPS derivatives possessed
      considerable neuroprotective and anticomplement activities and had stronger
      activities than FPS in certain tests. The in vitro results found that sulfated
      and benzoylated derivatives could reverse the decreased mitochondrial activity
      and decreased lactate dehydrogenase (LDH) and reactive oxygen species (ROS)
      release induced by 6-hydroxydopamine (6-OHDA, P<0.01 or P<0.001), which provides
      further evidence that sulfate and benzoylate groups could enhance the
      neuroprotective activity of fucoidan. In anticomplement experiments, all samples
      showed anticomplement activity in both systems; however, the sulfated and
      benzoylated derivatives showed better activity than fucoidan, with higher
      molecular weights showing the strongest activity. Available data suggested that
      substituted groups of fucoidan played an important role on neuroprotective and
      anticomplement activities. The mechanism of the influence of the neuroprotective
      and anticomplement activities of samples of the substituted groups was indicated.

PMID- 29462679
TI  - Novel pH sensitive dual drug loaded-gelatin methacrylate/methacrylic acid
      hydrogel for the controlled release of antibiotics.
AB  - The aim of the present study was to develop a novel pH sensitive gelatin
      methacrylate hydrogel for the controlled delivery of Gentamicin (GS) and
      Ampicillin (Amp). GS and Amp having synergistic activity is effective in killing
      multi drug resistant bacteria. The hydrogel was well characterized using FTIR,
      XRD and SEM techniques. The drug loading and encapsulation efficiency were found
      to be 85.0 and 77.0% for GS, 79.0 and 88.0% for Amp, respectively. The in vitro
      swelling, degradation and release profiles suggest the pH dependent behaviour of
      hydrogel. DPPH Assay confirmed the role of 2-amino guanidine in nullifying the
      side effect of GS and inhibition percentage of DDLHG is found to be 85.0%.
      Antimicrobial studies revealed the increased efficiency of the drug combination
      in killing bacteria.

PMID- 29462680
TI  - Thermal unfolding of human lysozyme induces aggregation: Recognition of the
      aggregates by antisera against the native protein.
AB  - Protein aggregates are formed due to the inappropriate folding of polypeptides.
      Human lysozyme (HLZ) plays an important role in the innate immune response of the
      body and has been used extensively as a model protein to study aggregation. In
      this study, we showed that HLZ undergoes unfolding induced aggregation when
      heated by using spectroscopic and microscopic techniques. We further showed that
      the aggregates were recognized by polyclonal antibodies against the native HLZ.
      The consequences of these observations are further co-related with mammalian
      physiology.

PMID- 29462681
TI  - Expression of vascular endothelial growth factor in cardiac repair: Signaling
      mechanisms mediating vascular protective effects.
AB  - The present study was aimed to investigate the vascular endothelial growth factor
      expression pattern in acute myocardial infarction induced rats. Serum level of
      vascular endothelial growth factor and its mRNA expression in myocardium were
      determined. Protein expression of vascular endothelial growth factor and
      endothelial nitric oxide synthase were measured. Serum level of vascular
      endothelial growth factor was increased 105.3, 260, 378.2 and 271.3% following
      the onset of acute myocardial infarction at 3, 6, 9 and 12days respectively. The
      mRNA and protein expression of vascular endothelial growth factor was
      substantially increased following the onset of acute myocardial infarction.
      Protein expression of endothelial nitric oxide synthase was increased up to 1.02
      fold. Taking all these data together, it is concluded that the vascular
      endothelial growth factor was increased in serum and tissue and attained peak at
      9th day following the onset of acute myocardial infarction. Increased vascular
      endothelial growth factor level in serum and tissue could increase endothelial
      cell proliferation and angiogenesis, and endothelial nitric oxide synthase could
      inhibit apoptosis and protect cardiomyocytes. In conclusion, the increased
      vascular endothelial growth factor expression could play an essential role in
      cardiac repair following the onset of acute myocardial infarction.

PMID- 29462682
TI  - Modulation of Kv3.1b potassium channel level and intracellular potassium
      concentration in 158N murine oligodendrocytes and BV-2 murine microglial cells
      treated with 7-ketocholesterol, 24S-hydroxycholesterol or tetracosanoic acid
      (C24:0).
AB  - Little is known about K+ regulation playing major roles in the propagation of
      nerve impulses, as well as in apoptosis and inflammasome activation involved in
      neurodegeneration. As increased levels of 7-ketocholesterol (7KC), 24S
      hydroxycholesterol (24S-OHC) and tetracosanoic acid (C24:0) have been observed in
      patients with neurodegenerative diseases, we studied the effect of 24 and/or 48 h
      of treatment with 7KC, 24S-OHC and C24:0 on Kv3.1b potassium channel level,
      intracellular K+ concentration, oxidative stress, mitochondrial dysfunction, and
      plasma membrane permeability in 158N oligodendrocytes and BV-2 microglial cells.
      In 158N cells, whereas increased level of Kv3.1b was only observed with 7KC and
      24S-OHC but not with C24:0 at 24 h, an intracellular accumulation of K+ was
      always detected. In BV-2 cells treated with 7KC, 24S-OHC and C24:0, Kv3.1b level
      was only increased at 48 h; intracellular K+ accumulation was found at 24 h with
      7KC, 24S-OHC and C24:0, and only with C24:0 at 48 h. Positive correlations
      between Kv3.1b level and intracellular K+ concentration were observed in 158N
      cells in the presence of 7KC and 24S-OHC, and in 7KC-treated BV-2 cells at 48 h.
      Positive correlations were also found between Kv3.1b or the intracellular K+
      concentration, overproduction of reactive oxygen species, loss of transmembrane
      mitochondrial potential and increased plasma membrane permeability in 158N and BV
      2 cells. Our data support that the lipid environment affects Kv3.1b channel
      expression and/or functionality, and that the subsequent rupture of K+
      homeostasis is relied with oligodendrocytes and microglial cells damages.

PMID- 29462683
TI  - Overcoming the polycation dilemma - Explorative studies to characterise the
      efficiency and biocompatibility of newly designed lipofection reagents.
AB  - In this explorative study of the novel cationic lipid OO4 in two different
      formulations the complex formation with DNA, the biopharmaceutical stability of
      the lipid/DNA complexes in physiological media, and the transfection efficiency
      were analysed. We investigated liposomes composed of two binary mixtures of OO4
      with either DOPE or DPPE as co-lipids in the molar ratio of 1:3. These
      formulations were compared with regard to their ability to bind the DNA using gel
      retardation electrophoresis, ethidium bromide exclusion and zeta potential
      measurements. Colloidal stability of the lipoplexes in foetal bovine serum (FBS)
      and the protective effect against degradation by endonucleases were studied.
      Furthermore, the influence of different salt concentrations on the complex
      formation with DNA was examined. The DOPE mixture was markedly superior compared
      to the DPPE mixture. Finally, haemocompatibility studies and gene silencing
      experiments were performed on OO4:DOPE 1:3 (n:n). The experiments demonstrate
      that the lipoplex formulation OO4:DOPE 1:3 (n:n) at N/P 4 is a promising
      candidate for systemic application because of the high colloidal stability in
      serum without PEGylated lipids, high transfection efficiency, superior resistance
      against nucleases, reproducible complexation independent of ionic effects, and
      haemocompatibility.

PMID- 29462684
TI  - Self-microemulsifying drug delivery system for camptothecin using new bicephalous
      heterolipid with tertiary-amine as branching element.
AB  - Camptothecin (CPT) has a potent and broad-spectrum anti-tumor activity but its
      clinical use is limited due to its poor water solubility, stability at
      physiological conditions and toxicity. The aim of our study was to evaluate
      bicephalous heterolipid E1E for enhancing the solubility and stability of CPT
      through the development of a self-microemulsifying drug delivery system (SMEDDS).
      The solubility of CPT in heterolipid E1E was found to be 82 and 5.86 folds higher
      than oleic acid and ethyl oleate respectively. Molecular dynamic simulation (MDS)
      studies revealed that stability of hydrogen bonding between CPT with E1E
      contributed to solubility enhancement of CPT. SMEDDS of CPT with heterolipid E1E
      as an oil phase was prepared and evaluated for drug loading, droplet size,
      morphology, thermodynamic and long-term stability studies as per ICH guidelines.
      The product, CPT-SMEDDS Fc showed 1.75 mg CPT loading per 1 g of SMEDDS having a
      droplet size of 20.93 +/- 0.41 nm. CPT-SMEDDS Fc was found to be stable,
      equipotent as compared to doxorubicin and had low toxicity in HeLa, MCF-7, and HL
      60 cell lines. These results signify that the delivery system, CPT-SMEDDS Fc
      could be a very good candidate to be considered for preclinical and clinical
      investigations.

PMID- 29462685
TI  - Topical bio(in)equivalence of metronidazole formulations in vivo.
AB  - The topical bioavailabilities of metronidazole from a commercially available
      'reference' product (Rozex(r)) and two extemporaneous test formulations were
      compared. With the reference drug product, a full skin pharmacokinetic profile,
      in vivo in human volunteers (following a 6-h uptake and clearance over the
      subsequent 22 h), was obtained using an improved stratum corneum (SC) sampling
      procedure. Then, a two-time point SC sampling method enabled the
      bio(in)equivalence of the test formulations to Rozex(r) to be evaluated. One test
      formulation was shown to be bioequivalent to Rozex(r), both for uptake and
      clearance, whereas the other (more viscous and less spreadable) formulation was
      not. The delivery of metronidazole into the underlying viable epidermal tissue
      from Rozex(r) and from the equivalent test formulation was 2.5 to 3.5-fold higher
      than that from the inequivalent extemporaneous vehicle. The results highlight
      that the quantitative composition of a formulation, as well as its physical
      properties that influence events that take place at the vehicle-skin interface,
      can have a dramatic impact on the delivery of drug into the SC and subsequently
      to the viable skin layers below. The reproducible, sensitive and facile in vivo
      methodology employed may prove of particular value where regulatory approval of
      generic formulations lacks objective rigour.

PMID- 29462686
TI  - PLGA nanoformulation of sparfloxacin enhanced antibacterial activity with
      photoprotective potential under ambient UV-R exposure.
AB  - Sparfloxacin (SPFX) is a broad spectrum antibiotic which inhibits bacterial DNA
      gyrase enzyme activity. However, photodegradation in the presence of UVA limits
      its antibacterial activity and induces phototoxicity. Thus, to encounter this
      problem, we have developed poly d,l-lactic-co-glycolic acid (PLGA) loaded SPFX
      nanoparticles. Here, we have performed a comparative antibacterial activity of
      SPFX and its nanoparticles (NPs) through molecular docking and plate sensitivity
      assay. Under environmental UVA exposure, photoexcited SPFX significantly
      generates ROS, DNA damage and mitochondrial mediated cell death in comparison to
      PLGA-SPFX-NPs (nano SPFX) in human skin cell line (HaCaT). In presence of UVA,
      bulk SPFX induced cell cycle arrest with appearance of sub-G1 peak showing
      apoptosis while nano SPFX did not show any change. SPFX triggered apoptosis via
      alteration in membrane integrity of mitochondria and lysosome in comparison to
      PLGA-SPFX-NPs. Involvement of mitochondrial mediated cell death was confirmed by
      down-regulation of anti-apoptotic Bcl-2 and procaspase-3 and upregulation of pro
      apoptotic Bax, cytochrome-c and caspase-3 proteins expression. Specific caspase
      inhibitor, Z-VAD-FMK showed involvement of caspase cascade pathway in apoptosis.
      Our finding suggests that controlled release of SPFX from PLGA-SPFX-NPs can
      reduce its side effects and enhance its antibacterial activity. Thus,
      nanotization of fluoroquinolones will be a significant step to reduce the problem
      of resistance and phototoxicity of this group.

PMID- 29462687
TI  - Recent advances on antimicrobial wound dressing: A review.
AB  - Skin and soft tissue infections (SSTIs) have high rates of morbidity and
      mortality associated. Despite the successful treatment of some SSTIs, those
      affecting the subcutaneous tissue, fascia, or muscle delay the healing process
      and can lead to life-threatening conditions. Therefore, more effective treatments
      are required to deal with such pathological situations. Recently, wound dressings
      loaded with antimicrobial agents emerged as viable options to reduce wound
      bacterial colonization and infection, in order to improve the healing process. In
      this review, an overview of the most prominent antibacterial agents incorporated
      in wound dressings along with their mode of action is provided. Furthermore, the
      recent advances in the therapeutic approaches used in the clinic and some future
      perspectives regarding antibacterial wound dressings are also discussed.

PMID- 29462688
TI  - Hierarchical drug release of pH-sensitive liposomes encapsulating aqueous two
      phase system.
AB  - As promising drug delivery vehicles, previous investigations of liposomes as
      carriers are primarily focused on insertion and modification of lipid membrane
      interfaces. The utility of the inner core seems to be overlooked. Herein, we
      developed pH-sensitive liposomes (PSLs) containing an aqueous two phase system
      (ATPS), and intriguingly discovered their hierarchical release under acidic
      stimuli. ATPS containing two polymers (poly(ethylene glycol) (PEG) and dextran)
      is homogeneous above phase transition temperature when producing ATPS-liposomes,
      and separated into PEG-rich phase and dextran-rich phase after cooling down to
      room temperature. The overall release time of ATPS-liposomes is divided into two
      stages and prolonged compared to simple aqueous liposomes. The unique release
      profile is due to the disproportional distribution of drugs in two phases.
      Doxorubicin (DOX) is loaded in the ATPS-liposomes, and their half maximum
      inhibition concentration on HeLa cells is 0.018 MUmol L-1, which means 27.5 fold
      increase in inhibition efficiency over free DOX.

PMID- 29462689
TI  - A hydroxyl PEG version of PEGylated liposomes and its impact on anti-PEG IgM
      induction and on the accelerated clearance of PEGylated liposomes.
AB  - Surface decoration of liposomes with polyethylene glycol (PEG), PEGylation, is
      recognized as a method to bestow liposomes with a prolonged circulation time
      following intravenous administration. However, many reports have emphasized that
      a first dose of PEGylated liposomes (PL) elicits an anti-PEG IgM antibody
      response that can trigger a rapid systemic clearance of a second dose of PL via a
      phenomenon that is referred to as "accelerated blood clearance (ABC)." Such a
      phenomenon is usually observed with PL that has been modified with methoxy-PEG.
      In the current study, we introduced various functional groups, methoxy (OCH3),
      amino (NH2), carboxyl (COOH), and hydroxyl (OH), at the chain ends of PEG to
      investigate the effect on anti-PEG IgM induction. Among different PEG-modified
      liposomes, hydroxyl PEG-modified liposomes (PL-OH) efficiently attenuated the
      anti-PEG IgM response in vitro. In addition, PL-OH was less recognizable by anti
      PEG IgM compared with other PLs. These findings raised the possibility that PL-OH
      could attenuate/abrogate elicitation of the ABC phenomenon. Nonetheless, upon
      repeated intravenous injection, PL-OH triggered the enhanced clearance of a
      subsequently injected second dose. Furthermore, in vitro studies have
      demonstrated that, as a complement activator, PL-OH is stronger than PL-OCH3 and
      induces further complement activation in the presence of anti-PEG IgM, which was
      the predominant contributor to the rapid clearance of a second dose of PL-OH. Our
      results suggest that the screening of complement activation by polymer-modified
      products in tandem with anti-polymer antibody production should be a prerequisite
      in the development of polymers that might enhance the therapeutic efficacy of
      nanocarriers.

PMID- 29462690
TI  - XPF plays an indispensable role in relieving silver nanoparticle induced DNA
      damage stress in human cells.
AB  - Due to the specific antimicrobial activity of silver nanoparticles (AgNPs), they
      are widely used in wound dressings, coatings in medical devices and household
      products. In spite of the well-documented genotoxicity of AgNPs, the molecular
      mechanisms of relieving AgNP-induced DNA damage stress remain poorly understood.
      We report here that one of the DNA repair factors, XPF, plays a crucial role in
      resisting AgNP-induced DNA damage stress in human cells. Following culture with
      AgNP-containing media, severely decreased colony forming abilities have been
      observed in XPF mutant and knockdown cells compared with wild type or control
      cells respectively, demonstrating that XPF is required to resist the AgNP-induced
      stress. By employing the comet assays, we confirmed that DNA damages were
      produced in all tested cells following their exposure to AgNPs for 48 h. However,
      more DNA damage accumulations were observed in XPF mutant and knockdown cells
      than wild type or control cells respectively. Moreover, severe DNA damage
      response and the activation of p53-mediated DNA damage response network result
      from mutated XPF or significantly reduced XPF level in human cells. Together, our
      results illustrate that XPF is the indispensable factor involved in relieving
      AgNP-induced DNA damage stress in human cells.

PMID- 29462691
TI  - Factor X activating Atractaspis snake venoms and the relative coagulotoxicity
      neutralising efficacy of African antivenoms.
AB  - Atractaspis snake species are enigmatic in their natural history, and venom
      effects are correspondingly poorly described. Clinical reports are scarce but
      bites have been described as causing severe hypertension, profound local tissue
      damage leading to amputation, and deaths are on record. Clinical descriptions
      have largely concentrated upon tissue effects, and research efforts have focused
      upon the blood-pressure affecting sarafotoxins. However, coagulation disturbances
      suggestive of procoagulant functions have been reported in some clinical cases,
      yet this aspect has been uninvestigated. We used a suite of assays to investigate
      the coagulotoxic effects of venoms from six different Atractaspis specimens from
      central Africa. The procoagulant function of factor X activation was revealed, as
      was the pseudo-procoagulant function of direct cleavage of fibrinogen into weak
      clots. The relative neutralization efficacy of South African Antivenom Producer's
      antivenoms on Atractaspis venoms was boomslang>>>polyvalent>saw-scaled viper.
      While the boomslang antivenom was the most effective on Atractaspis venoms, the
      ability to neutralize the most potent Atractaspis species in this study was up to
      4-6 times less effective than boomslang antivenom neutralizes boomslang venom.
      Therefore, while these results suggest cross-reactivity of boomslang antivenom
      with the unexpectedly potent coagulotoxic effects of Atractaspis venoms, a
      considerable amount of this rare antivenom may be needed. This report thus
      reveals potent venom actions upon blood coagulation that may lead to severe
      clinical effects with limited management strategies.

PMID- 29462692
TI  - The promotion on cell growth of androgen-dependent prostate cancer by antimony
      via mimicking androgen activity.
AB  - Antimony is a widely used heavier pnictogens in industry, and its toxicity has
      been a matter of concern. Although previous studies have suggested that antimony
      may have the function as either a tumor suppressor or an oncogene in several
      cancers, the molecular basis underlying antimony-mediated transformation is still
      unclear. In the current study, we attempt to elucidate the potential role of
      antimony in the development of prostate cancer. Our results showed that the
      concentration of antimony was much higher in serum of prostate cancer patients,
      and was closely associated with poor outcome of patients who underwent radical
      prostatectomy. Additionally, low dose of antimony could promote proliferation and
      invasion of androgen-dependent prostate cancer cell line LNCaP cells in vitro and
      in vivo. The mechanistic studies demonstrated that exposure to antimony triggered
      the phosphorylation of androgen receptor (AR), which transcriptionally regulates
      the expression of androgen-related targets, including PSA and NKX3.1. Overall,
      our results unearthed that antimony could promote tumor growth by mimicking
      androgen activity in androgen-dependent prostate cancer cells. Therefore, these
      findings expanded our understanding on the molecular mechanism of antimony in
      tumorigenesis and tumor progression of prostate cancer, and it appears to be an
      inspiring strategy to restrain prostate cancer by inhibiting antimony-induced
      androgen-like effects.

PMID- 29462693
TI  - Two novel dual GLP-1/GIP receptor agonists are neuroprotective in the MPTP mouse
      model of Parkinson's disease.
AB  - Type 2 diabetes mellitus (T2DM) is a risk factors for developing Parkinson's
      disease (PD). Insulin desensitization is observed in the brains of PD patients,
      which may be an underlying mechanism that promotes neurodegeneration. Incretin
      hormones are growth factors that can re-sensitize insulin signalling. We have
      previously shown that analogues of the incretins GLP-1 or GIP have
      neuroprotective effects in the MPTP mouse model of PD. Novel dual GLP-1/GIP
      receptor agonists have been developed as treatments for T2DM. We have tested 3
      novel dual receptor agonists DA-JC1, DA-JC4 and DA-CH5 in comparison with the GLP
      1 analogue liraglutide (all drugs at 25 nmol/kg ip once-daily for 6 days) in the
      MPTP mouse model of PD (4 * 25 mg/kg ip). In the Rotarod and grip strength
      assessment, DA-CH5 performed best in reversing the MPTP-induced motor impairment.
      Dopamine synthesis as indicated by levels of tyrosine hydroxylase was much
      reduced by MPTP in the substantia nigra and striatum, and DA-CH5 was the best
      drug to reverse this. Pro-inflammatory cytokines were best reduced by DA-CH5,
      while expression levels of the neuroprotective growth factor Glial-Derived
      Neurotrophic Factor (GDNF) was most increased by DA-JC4. Synapses were protected
      best by DA-JC4 and DA-CH5. Both DA-JC1 and liraglutide showed inferior effects.
      These results show that a combination of GLP-1 and GIP receptor activation is
      more efficient compared to single GLP-1 receptor activation. We conclude that
      dual agonists are a promising novel treatment for PD. The GLP-1 mimetic exendin-4
      has previously shown disease modifying effects in two clinical trials in
      Parkinson patients.

PMID- 29462694
TI  - Effects of pre-reproductive maternal enrichment on maternal care, offspring's
      play behavior and oxytocinergic neurons.
AB  - Potentiating social, cognitive, and sensorimotor stimulations the Environmental
      Enrichment (EE) increases levels of novelty and complexity experienced by
      individuals. Growing evidence demonstrates that parental EE experience, even
      occurring in the pre-reproductive phase, affects behavioral and neural
      developmental trajectories of the offspring. To discover how the accumulation of
      early maternal complex experiences may inform and shape the social behavior of
      the following generation, we examined the effects of pre-reproductive enrichment
      of dams (post-natal days 21-72) on the play performances of their male and female
      adolescent offspring. Furthermore, we examined the effects of pre-reproductive
      enrichment on maternal behavior (during post-partum days 1-10) and male intruder
      aggression (on post-partum day 11). Since oxytocin modulates maternal care,
      social bonding, and agonistic behavior, the number of oxytocinergic neurons of
      the paraventricular (PVN) and supraoptic (SON) nuclei was examined in both dams
      and offspring. Results revealed that enriched females exhibited higher levels of
      pup-oriented behaviors, especially Crouching, and initiated pup-retrieval more
      quickly than standard females after the maternal aggression test. Such behavioral
      peculiarities were accompanied by increased levels of oxytocinergic neurons in
      PVN and SON. Moreover, pre-reproductive maternal EE cross-generationally
      influenced the offspring according to sex. Indeed, male pups born to enriched
      females exhibited a reduced play fighting associated with a higher number of
      oxytocinergic neurons in SON in comparison to male pups born to standard-housed
      females. In conclusion, pre-reproductive EE to the mothers affects their maternal
      care and has a cross-generational impact on the social behavior of their
      offspring that do not directly experiences EE.

PMID- 29462695
TI  - A 3D intestinal tissue model supports Clostridioides difficile germination,
      colonization, toxin production and epithelial damage.
AB  - Endospore-forming Clostridioides difficile is a causative agent of antibiotic
      induced diarrhea, a major nosocomial infection. Studies of its interactions with
      mammalian tissues have been hampered by the fact that C. difficile requires
      anaerobic conditions to survive after spore germination. We recently developed a
      bioengineered 3D human intestinal tissue model and found that low O2 conditions
      are produced in the lumen of these tissues. Here, we compared the ability of C.
      difficile spores to germinate, produce toxin and cause tissue damage in our
      bioengineered 3D tissue model versus in a 2D transwell model in which human cells
      form a polarized monolayer. 3D tissue models or 2D polarized monolayers on
      transwell filters were challenged with the non-toxin producing C. difficile CCUG
      37787 serotype X (ATCC 43603) and the toxin producing UK1 C. difficile spores in
      the presence of the germinant, taurocholate. Spores germinated in both the 3D
      tissue model as well as the 2D transwell system, however toxin activity was
      significantly higher in the 3D tissue models compared to the 2D transwells.
      Moreover, the epithelium damage in the 3D tissue model was significantly more
      severe than in 2D transwells and damage correlated significantly with the level
      of toxin activity detected but not with the amount of germinated spores.
      Combined, these results show that the bioengineered 3D tissue model provides a
      powerful system with which to study early events leading to toxin production and
      tissue damage of C. difficile with mammalian cells under anaerobic conditions.
      Furthermore, these systems may be useful for examining the effects of microbiota,
      novel drugs and other potential therapeutics directed towards C. difficile
      infections.

PMID- 29462696
TI  - Revealing the parasitic infection in diarrheic yaks by piloting high-throughput
      sequencing.
AB  - Diarrhea a serious disease, reported to be related with changes in microbial
      diversity is widely epidemic in the yaks on the Qinghai Tibet plateau. Herein, we
      preformed high-throughput sequencing of the parasitic diversity in 3 groups of
      yaks i.e. healthy adult yaks (HA), diarrheic adult yaks (DA) and diarrheic yak
      calves (DC) in Gannan Tibetan Autonomous Prefecture. The results showed that 2
      Phyla, 3 Classes, 5 Orders, 4 Families and 6 Genera were discovered in HA yaks; 2
      Phyla, 3 Classes, 6 Orders, 6 Families and 8 Genera were found in DA yaks while 2
      Phyla, 5 Classes, 5 Orders, 10 Families and 7 Genera were observed in DC yaks. At
      Phylum level, Nematoda and Apicomplexa were detected in all three yak groups;
      however, Apicomplexa was found to be conspicuously higher in the DC yaks as
      compared to DA yaks (p < 0.05). At Class level, Litostomatea, Chromadorea and
      Gregarinasina were found in all three yak groups, while Spirotrichea and Colpodea
      were only found in the DC yaks. At Order level, Vestibuliferida,
      Tritrichomonadida, Rhabditida and Eugregarinorida were observed in all three yak
      groups; and Neogregarinorida was noted HA and DC yaks while Trichomonadida and
      Hypotrichomonadida were only found in DA yaks. Tritrichomonadida was found to be
      relatively higher in the DA yaks when compared with HA yaks (p < 0.05) and DC
      yaks (p < 0.05). At Family level, Simplicimonadidae and Haemonchidae were found
      in all three yak groups. Trichostrongylidae was observed in both HA and DA yak
      groups. Syncystidae was established in both HA and DC yak groups except DA yaks.
      Trichomonadidae and Dictyocaulidae were only found in DA yaks. Plectidae,
      Strongylidae, Echinamoebidae, Lecudinidae, Pseudokeronopsidae and Panagrolaimidae
      were only discovered in DC yaks. Simplicimonadidae was found to be remarkably
      higher in DA yaks as compared to HA and DC yak groups (p < 0.05); and
      Haemonchidae was detected at higher levels in HA yaks as compared to DA and DC
      yaks (p < 0.05). At Genus level, Entamoeba, Buxtonella and Haemonchus were found
      in all three yak groups. Plectus and Echinamoeba were only found in DC yaks;
      while Trichostrongylus and Trepomonas were observed in HA and DA yak groups. The
      genus Gregarina was found in both diarrheic yak groups; while the genera of
      Tetratrichomonas and Dictyocaulus were observed in DA yaks only. The present
      study herein reported an insight of the change of parasitic diversity in
      diarrheic yaks at high altitude area, which shall make contribution towards the
      solid prevention of diarrhea in yaks.

PMID- 29462697
TI  - Effect of Mycobacterium tuberculosis Rv3717 on cell division and cell adhesion.
AB  - Mycobacterium tuberculosis Rv3717 has been identified as a zinc-dependent amidase
      which can hydrolyze peptidoglycan (PG). To demonstrate the relationship of Rv3717
      and cell division, in this study, Rv3717 gene was first amplified and expressed
      and the resulting protein was purified by using a His-tagged approach. M.
      smegmatis mc2155, a fast-growing and nonpathogenic mycobacterium was used to
      evaluate the effect of Rv3717 on cell division. Scan electron microscope (SEM)
      results indicated that M. smegmatis with division site was more exhibited and
      some of the cells turned larger in size after Rv3717 treatment. Transmission
      electron microscope (TEM) results revealed that MSMEG_6281 gene knockout strain
      named M sm-DeltaM_6281 (MSMEG_6281 in M. smegmatis mc2155 is the homologous gene
      of Rv3717) tended to have a division defect with a severely abnormal morphology,
      and division septa were distorted. Gene expression analysis indicated also that
      the gene involved in cell division such as M. smegmatis ftsZ was significantly up
      regulated with treatment time. The findings demonstrated that physiological role
      of Rv3717 was related to cell division and regulated possibly division septum
      formation. Further, fibronectin (Fn) binding ability of Rv3717 was evaluated by
      protein binding experiment, and the results confirmed the interaction of Rv3717
      with Fn in a dose dependent manner. We found also that the invasion rate of M. sm
      DeltaM_6281 to A549 cells was reduced by 59% compared to the control strain, and
      the invasion defect could be rescued by Rv3717 addition. RT-PCR results showed
      that M. smegmatis fbpC were up-regulated after Rv3717 addition. These clues may
      be significant to explore roles of Rv3717 in growth and colonization of
      mycobacteria.

PMID- 29462698
TI  - Piper sarmentosum Roxb. confers neuroprotection on beta-amyloid (Abeta)-induced
      microglia-mediated neuroinflammation and attenuates tau hyperphosphorylation in
      SH-SY5Y cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum Roxb. (PS), belonging to
      Piperaceae family, is an edible plant with medicinal properties. It is
      traditionally used by the Malays to treat headache and boost memory.
      Pharmacological studies revealed that PS exhibits anti-inflammatory, anti
      oxidant, anti-acetylcholinesterase, and anti-depressant-like effects. In view of
      this, the present study aimed to investigate the anti-inflammatory actions of PS
      and its potential neuroprotective effects against beta-amyloid (Abeta)-induced
      microglia-mediated neurotoxicity. MATERIALS AND METHODS: The inhibitory effects
      of hexane (LHXN), dichloromethane (LDCM), ethyl acetate (LEA) and methanol
      (LMEOH) extracts from leaves of PS on Abeta-induced production and mRNA
      expression of pro-inflammatory mediators in BV-2 microglial cells were assessed
      using colorimetric assay with Griess reagent, ELISA kit and real-time RT-PCR
      respectively. Subsequently, MTT reduction assay was used to evaluate the
      neuroprotective effects of PS leaf extracts against Abeta-induced microglia
      mediated neurotoxicity in SH-SY5Y neuroblastoma cells. The levels of tau proteins
      phosphorylated at threonine 231 (pT231) and total tau proteins (T-tau) were
      determined using ELISA kits. RESULTS: Polar extracts of PS leaves (LEA and LMEOH)
      reduced the Abeta-induced secretion of pro-inflammatory cytokines (IL-1beta and
      TNF-alpha) in BV-2 cells by downregulating the mRNA expressions of pro
      inflammatory cytokines. The inhibition of nitric oxide (NO) production could be
      due to the free radical scavenging activity of the extracts. In addition,
      conditioned media from Abeta-induced BV-2 cells pre-treated with LEA and LMEOH
      protected SH-SY5Y cells against microglia-mediated neurotoxicity. Further
      mechanistic study suggested that the neuroprotective effects were associated with
      the downregulation of phosphorylated tau proteins. CONCLUSIONS: The present study
      suggests that polar extracts of PS leaves confer neuroprotection against Abeta
      induced microglia-mediated neurotoxicity in SH-SY5Y cells by attenuating tau
      hyperphosphorylation through their anti-inflammatory actions and could be a
      potential therapeutic agent for Alzheimer's disease.

PMID- 29462699
TI  - Effect of Eucommia ulmoides Oliv., Gynostemma pentaphyllum (Thunb.) Makino, and
      Curcuma longa L. on Th1- and Th2-cytokine responses and human leukocyte antigen
      DR expression in peripheral blood mononuclear cells of septic patients.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Many traditional Chinese medicines (TCM), such as
      Eucommia ulmoides Oliv., Gynostemma pentaphyllum (Thunb.) Makino, and Curcuma
      longa L., have been reported to have various immune-modulatory effects. AIM OF
      THE STUDY: To determine the effects of extracts from these three TCM on type 1 T
      help (Th1)- and Th2-cytokine responses and human leukocyte antigen (HLA)-DR
      expression in peripheral blood mononuclear cells (PBMCs) obtained from septic
      patients. MATERIALS AND METHODS: Lipopolysaccharide (LPS)-stimulated PBMCs of
      healthy controls and septic patients were cultured for 48 hs with or without
      0.05/0.1 mg/ml of TCM extract. HLA-DR expression in monocytes was detected using
      flow cytofluorimetry. The interferon [IFN]-gamma, tumor necrosis factor [TNF]
      alpha, interleukin (IL)- 2, IL-5, IL-10, and IL-13 levels in supernatants were
      measured with a human enzyme-linked immunosorbent assay. RESULTS: Treatment with
      either 0.05 or 0.1 mg/ml of C. longa L. extract significantly restored the
      percentage of HLA-DR-positive monocytes, which was decreased by LPS in control
      and patient groups. Treatment with 0.05 or 0.1 mg/ml E. ulmoides Oliv. and
      C.longa L. extract decreased IL-10 production from LPS-stimulated PBMCs of
      controls and patients. In patients with sepsis, C. longa L. extract decreased IL
      10 production to a greater degree than did E. ulmoides Oliv extract. Although IFN
      gamma, TNF-alpha, or IL-13 productions from LPS-stimulated PBMCs were influenced
      by E. ulmoides Oliv., G. pentaphyllum (Thunb.) Makino, or C. longa L. in control
      or sepsis groups in this study, only the influence of IL-10 was consistent in
      both control and sepsis groups. CONCLUSIONS: By enhancing monocyte HLA-DR
      expression and decreasing IL-10 production, C. longa L. might help restore
      inflammatory responses in septic patients to eradicate pathogens.

PMID- 29462700
TI  - Eugenia brasiliensis leaves extract attenuates visceral and somatic inflammatory
      pain in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Eugenia brasiliensis Lam. (Myrtaceae) is a
      Brazilian tree distributed throughout Atlantic rain forest, since Bahia until
      Santa Catarina state, and is popularly known as "grumixaba, grumixameira,
      cumbixaba, ibaporoiti, and cereja-brasileira". The bark and leaves of Eugenia
      brasiliensis are used in folk medicine as adstringent, diuretic, energizing, anti
      rheumatic and anti-inflammatory. This study aimed at investigating the chemical
      composition, antinociceptive and anti-inflammatory effect of the hydroalcoholic
      extract of Eugenia brasiliensis (HEEb). MATERIAL AND METHODS: Chemical
      composition of the HEEb was determined by High Performance Liquid
      Chromatography/ESI-Mass Spectrometry (HPLC-ESI-MS/MS). The antinociceptive and
      anti-inflammatory effects of HEEb (30-300 mg/kg) was verified in mice after oral
      administration by intra-gastric gavage (i.g.) 60 min prior to experimentation. It
      was investigated whether HEEb decreases visceral pain and leukocyte migration
      induced by an intraperitoneal (i.p.) injection of acetic acid (0.6%). We also
      evaluated whether HEEb decreases nociceptive behavior induced by formalin
      (including paw edema and temperature), prostaglandin E2 (PGE2), histamine, and
      compound 48/80. Finally, we evaluated the effect of HEEb in the chronic
      inflammatory (mechanical and thermal hypersensitivity) pain induced by complete
      Freund's adjuvant (CFA), as well as quantifying the concentration of the pro
      inflammatory cytokines TNF-alpha and IL-6 in the paw by ELISA method. RESULTS:
      Seven polyphenols were identified in HEEb by HPLC-ESI-MS/MS analysis. HEEb
      treatment alleviated nocifensive behavior and leukocyte migration caused by
      acetic acid. Moreover, HEEb also reduced the inflammatory pain and paw
      temperature induced by formalin, as well as it decreased nociceptive behavior
      induced by histamine and compound 48/80. Finally, acute and repeated treatment of
      animals with HEEb (100 mg/kg, i.g.) markedly reduced the mechanical and thermal
      (heat) hypersensitivity, besides decrease paw edema and temperature induced by
      CFA, and this effect was evident until the day 7. Moreover, repeated treatment
      with HEEb (100 mg/kg, i.g.) significantly reduced the levels of IL-6 and TNF
      alpha in the paw when compared to the CFA group. CONCLUSIONS: This is the first
      report showing that HEEb presents antinociceptive and anti-inflammatory effects
      in the visceral and somatic inflammatory pain in mice, possibly involving the
      inhibition of histamine receptors and pro-inflammatory cytokines activated
      pathways. Our results are of interest because they support the use of Eugenia
      brasiliensis as a potential source of phytomedicine for inflammatory diseases and
      pain.

PMID- 29462701
TI  - Quantitative Comparison Of Vesicular Glutamate Transporters in rat Deep
      Cerebellar Nuclei.
AB  - The excitatory synapses of the rat deep cerebellar nuclei (DCN) were
      quantitatively analyzed by vesicular glutamate transporter 1 and 2 (vGluT1 and
      vGluT2) immunolabeling. We calculated the number and sizes of the labeled boutons
      and compared them between lateral/dentate nucleus (LN/DN), posterior interposed
      nucleus (PIN), anterior interposed nucleus (AIN), and medial nucleus (MN). The
      density of vGluT1+ boutons differs significantly within these nuclei. In
      contrast, the vGluT2+ bouton density is more similar between different nuclei.
      The phylogenetically newer DCN (LN/DN and PIN) have a 39% higher density of
      vGluT1+ boutons than the phylogenetically older DCN (AIN and MN). The volume of
      vGluT1+ boutons does not differ between the DCN, however the average volume of
      vGluT2+ boutons is larger in MN. In summary, our current results confirm and
      extend our previous findings showing that the increase in dendritic and axonal
      wiring in phylogenetically newer DCN is associated with an increase in vGluT1+
      bouton density.

PMID- 29462703
TI  - Lifelong Aerobic Exercise Reduces the Stress Response in Rats.
AB  - The aim of this study was to analyze the effects of lifelong aerobic exercise
      (AE) on the adaptive response of the stress system in rats. It is well known that
      hypothalamic-pituitary-adrenal axis (HPA) activity differs when triggered by
      voluntary or forced exercise models. Male Wistar rats belonging to exercise (E)
      or control (C) groups were subjected to chronic AE, and two cutoff points were
      established at 8 (middle age) and 18 months (old age). Behavioral, biochemical
      and histopathological studies were performed on the main components/targets of
      the stress system. AE increased adrenal sensitivity (AS), brain corticosterone
      (CORT) and corticotropin-releasing factor (CRF), but had no effect on the thymus,
      adrenal glands (AGs) weight or plasma CORT. In addition, AE exerted no effect on
      the sympathetic tone, but significantly reduced anxiety-related behavior and
      emotionality. Aging decreased AS and deregulated neuroendocrine feedback, leading
      to an anxiogenic state which was mitigated by AE. Histopathological and
      morphometric analysis of AGs showed no alterations in middle-aged rats but
      adrenal vacuolization in approximately 20% old rats. In conclusion, lifelong AE
      did not produce adverse effects related to a chronic stress state. On the
      contrary, while AE upregulated some components of the HPA axis, it generated an
      adaptive response to cumulative changes, possibly through different compensatory
      and/or super compensatory mechanisms, modulated by age. The long-term practice of
      AE had a strong positive impact on stress resilience so that it could be
      recommended as a complementary therapy in stress and depression disease.

PMID- 29462702
TI  - Cell Type-specific Intrinsic Perithreshold Oscillations in Hippocampal GABAergic
      Interneurons.
AB  - The hippocampus plays a critical role in learning, memory, and spatial processing
      through coordinated network activity including theta and gamma oscillations.
      Recent evidence suggests that hippocampal subregions (e.g., CA1) can generate
      these oscillations at the network level, at least in part, through GABAergic
      interneurons. However, it is unclear whether specific GABAergic interneurons
      generate intrinsic theta and/or gamma oscillations at the single-cell level.
      Since major types of CA1 interneurons (i.e., parvalbumin-positive basket cells
      (PVBCs), cannabinoid type 1 receptor-positive basket cells (CB1BCs), Schaffer
      collateral-associated cells (SCAs), neurogliaform cells and ivy cells) are
      thought to play key roles in network theta and gamma oscillations in the
      hippocampus, we tested the hypothesis that these cells generate intrinsic
      perithreshold oscillations at the single-cell level. We performed whole-cell
      patch-clamp recordings from GABAergic interneurons in the CA1 region of the mouse
      hippocampus in the presence of synaptic blockers to identify intrinsic
      perithreshold membrane potential oscillations. The majority of PVBCs (83%), but
      not the other interneuron subtypes, produced intrinsic perithreshold gamma
      oscillations if the membrane potential remained above -45 mV. In contrast,
      CB1BCs, SCAs, neurogliaform cells, ivy cells, and the remaining PVBCs (17%)
      produced intrinsic theta, but not gamma, oscillations. These oscillations were
      prevented by blockers of persistent sodium current. These data demonstrate that
      the major types of hippocampal interneurons produce distinct frequency bands of
      intrinsic perithreshold membrane oscillations.

PMID- 29462704
TI  - Enhancement of Endocannabinoid-dependent Depolarization-induced Suppression of
      Excitation in Glycinergic Neurons by Prolonged Exposure to High Doses of
      Salicylate.
AB  - The Dorsal Cochlear Nucleus (DCN) is a region which has been traditionally linked
      to the genesis of tinnitus, the constant perception of a phantom sound. Sodium
      salicylate, a COX-2 inhibitor, can induce tinnitus in high doses. Hyperactivity
      of DCN neurons is observed in several animal models of tinnitus, including
      salicylate-induced tinnitus. The DCN presents several forms of endocannabinoid
      (EC)-dependent synaptic plasticity and COX-2 can also participate in the
      oxidative degradation of ECs. We recently demonstrated that short-term perfusion
      of sodium salicylate and other inhibitors of both oxidative and hydrolytic EC
      degradation did not affect depolarization-induced suppression of excitation
      (DSE), a form of EC-dependent short-term synaptic plasticity. Here, we show that
      prolonged incubation with high doses of sodium salicylate (1.4 mM) enhances DSE
      of synapses onto glycinergic DCN interneurons but not those innervating
      glutamatergic DCN fusiform neurons. This effect was not reproduced with lower
      doses of salicylate (140 uM) or with ibuprofen, another inhibitor of COX-2. This
      effect was not observed in the presence of AM251, an antagonist/inverse agonist
      of cannabinoid CB1 receptors, showing that it was dependent on EC release.
      Finally we demonstrated that incubation with salicylate potentiated the increase
      in intracellular calcium during the depolarization. Our results point to an
      increased inhibition of DCN inhibitory CW neuron during depolarizations, probably
      by an enhanced EC release during the depolarizations, which is potentially
      significant for DCN hyperactivity and tinnitus generation.

PMID- 29462705
TI  - Nitric Oxide and Mitochondrial Function in Neurological Diseases.
AB  - Mitochondria are key cellular organelles that play crucial roles in the energy
      production and regulation of cellular metabolism. Accumulating evidence suggests
      that mitochondrial activity can be modulated by nitric oxide (NO). As a key
      neurotransmitter in biologic systems, NO mediates the majority of its function
      through activation of the cyclic guanylyl cyclase (cGC) signaling pathway and S
      nitrosylation of a variety of proteins involved in cellular functioning including
      those involved in mitochondrial biology. Moreover, excess NO or the formation of
      reactive NO species (RNS), e.g., peroxynitrite (ONOO-), impairs mitochondrial
      functioning and this, in conjunction with nuclear events, eventually affects
      neuronal cell metabolism and survival, contributing to the pathogenesis of
      several neurodegenerative diseases. In this review we highlight the possible
      mechanisms underlying the noxious effects of excess NO and RNS on mitochondrial
      function including (i) negative effects on electron transport chain (ETC); (ii)
      ONOO--mediated alteration in mitochondrial permeability transition; (iii)
      enhanced mitochondrial fragmentation and autophagy through S-nitrosylation of key
      proteins involved in this process such as dynamin-related protein 1 (DRP-1) and
      Parkin/PINK1 (protein phosphatase and tensin homolog-induced kinase 1) complex;
      (iv) alterations in the mitochondrial metabolic pathways including Krebs cycle,
      glycolysis, fatty acid metabolism, and urea cycle; and finally (v) mitochondrial
      ONOO--induced nuclear toxicity and subsequent release of apoptosis-inducing
      factor (AIF) from mitochondria, causing neuronal cell death. These proposed
      mechanisms highlight the multidimensional nature of NO and its signaling in the
      mitochondrial function. Understanding the mechanisms by which NO mediates
      mitochondrial (dys)function can provide new insights into the treatment of
      neurodegenerative diseases.

PMID- 29462706
TI  - Biomaterial Cues to Direct a Pro-regenerative Phenotype in Macrophages and
      Schwann Cells.
AB  - Following peripheral nerve injury (PNI), inflammatory cues impede repair. We have
      previously demonstrated that spinal cord matrix (SCM) proteins and hyaluronic
      acid (HA) nanofibers mitigate chondroitin sulfate proteoglycan (CSPG) inhibition
      and promote growth in peripheral neurons. In this study, we evaluated the effects
      of a characteristic CSPG, chondroitin sulfate A (CSA), SCM, and HA fibers on
      macrophages and Schwann cells (SCs). We hypothesized that our cues would
      accelerate the macrophages' return to rest following classical activation (M1/pro
      inflammatory) with lipopolysaccharide (LPS; 1 MUg/mL) and would accelerate the
      transformation of SCs from an immature state following injury to a mature/pro
      myelinating phenotype. LPS stimulation of the macrophages caused upregulation of
      inducible nitric oxide synthase (iNOS; M1 gene) and led to significantly
      increased cell area and decreased circularity. However, the SCM and HA nanofibers
      mitigated this effect, significantly reducing iNOS expression. SCs on the fibers
      had significantly reduced area and increased elongation. These morphological
      changes may have polarized the cells leading to decreased GFAP (immature gene)
      and increased Oct6 and Krox 20 (promyelin genes) expression. Antibody arrays were
      used to measure relative levels of inflammatory cytokines released by the cells.
      The arrays confirmed that anti-inflammatory cytokines are released from the cells
      when cultured with our biomaterial cues and helped identify targets for future
      investigation including vascular endothelial growth factor (VEGF), interleukin
      (IL)-10, monocyte colony stimulating factor (M-CSF) from the macrophages, Agrin,
      ciliary neurotrophic factor (CNTF), tissue inhibitor metalloproteinases (TIMPs)-1
      from SCs, and IL-2 from both cell types. In conclusion, these results suggest
      that our biomaterial cues have pro-regenerative effects on both cell types and if
      combined may trigger cells toward regenerative programs.

PMID- 29462707
TI  - The Diagnostic Value of Anti-Mullerian Hormone in Early Post Menarche Adolescent
      Girls with Polycystic Ovarian Syndrome.
AB  - STUDY OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a common endocrine
      disorder characterized by hyperandrogenism and chronic anovulation, which affects
      5%-10% of reproductive-age women. Diagnosis of adult patients with PCOS is made
      easily with clinical and laboratory methods and the anti-Mullerian hormone (AMH)
      level are accepted as a good indicator. However, there is still no complete
      consensus on the diagnosis of PCOS in adolescents. DESIGN AND SETTING:
      Prospective cohort study, December 2013 to November 2014. PARTICIPANTS: The study
      was conducted on adolescent girls with oligomenorrhea, with at least 2 years
      since menarche. The study group consisted of adolescent girls with complete PCOS
      and incomplete PCOS. A control group was formed of healthy adolescent girls.
      Complete PCOS was diagnosed according to the Rotterdam criteria, as the presence
      of all the following characteristics: oligomenorrhea, hyperandrogenism, and
      polycystic ovarian morphology on ultrasound image. Incomplete PCOS was accepted
      as "oligomenorrhea and polycystic ovarian morphology," or "oligomenorrhea and
      hyperandrogenism." INTERVENTIONS AND MAIN OUTCOME MEASURES: All patients
      underwent a physical examination and the anthropometric assessments, insulin
      resistance, and acanthosis nigricans were recorded. It was also noted whether or
      not the patient had an acne score. The Ferriman-Gallwey score was applied to
      evaluate hirsutism. RESULTS: The results of this study showed that no
      statistically significant difference was found between the PCOS and incomplete
      PCOS groups and the control group with respect to AMH levels. CONCLUSION: The use
      of adult-specific diagnostic methods in adolescence might result in an incomplete
      diagnosis and inadequate treatment plan. Although the serum AMH level clearly
      facilitates the diagnosis of PCOS, the use of the AMH level in adolescence in
      PCOS diagnosis is still controversial and further studies are needed.

PMID- 29462708
TI  - Diversity of Pubertal Development in Cartilage-Hair Hypoplasia; Two Illustrative
      Cases.
AB  - BACKGROUND: Cartilage-hair hypoplasia (CHH) is a rare chondrodysplasia, including
      disproportionate short stature, hypoplastic hair, immunodeficiency, and increased
      risk of malignancies. Absent pubertal growth spurt and absent pubic hair
      complicate monitoring of pubertal development in these patients. CASES: Two CHH
      patients with delayed puberty and excessive growth failure are described. One of
      the girls had hypogonadotropic hypogonadism whereas the other had
      hyponormogonadotropic hypogonadism with no spontaneous pubertal development and
      slow response to estrogen therapy, both requiring permanent replacement therapy.
      SUMMARY AND CONCLUSION: Careful follow-up of pubertal development in individuals
      with CHH and other growth-restricting bone diseases is needed. In delayed
      pubertal development timely hormone therapy is essential to ensure maximal growth
      and well developed secondary sex characteristics.

PMID- 29462710
TI  - Fibrin glue mesh fixation combined with mesenchymal stem cells or exosomes
      modulates the inflammatory reaction in a murine model of incisional hernia.
AB  - : Surgical meshes are effective and frequently used to reinforce soft tissues.
      Fibrin glue (FG) has been widely used for mesh fixation and is also considered an
      optimal vehicle for stem cell delivery. The aim of this preclinical study was to
      evaluate the therapeutic effect of MSCs and their exosomes combined with FG for
      the treatment of incisional hernia. A murine incisional hernia model was used to
      implant surgical meshes and different treatments with FG, MSCs and exo-MSCs were
      applied. The implanted meshes were evaluated at day 7 by anatomopathology,
      cellular analysis of infiltrating leukocytes and gene expression analysis of
      TH1/TH2 cytokines, MMPs, TIMPs and collagens. Our results demonstrated a
      significant increase of anti-inflammatory M2 macrophages and TH2 cytokines when
      MSCs or exo-MSCs were used. Moreover, the analysis of MMPs, TIMPs and collagen
      exerted significant differences in the extracellular matrix and in the remodeling
      process. Our in vivo study suggests that the fixation of surgical meshes with FG
      and MSCs or exo-MSCs will have a beneficial effect for the treatment of
      incisional hernia in terms of improved outcomes of damaged tissue, and
      especially, in the modulation of inflammatory responses towards a less aggressive
      and pro-regenerative profile. STATEMENT OF SIGNIFICANCE: The implantation of
      surgical meshes is the standard procedure to reinforce tissue defects such as
      hernias. However, an exacerbated and persistent inflammatory response secondary
      to this implantation is frequently observed, leading to a strong discomfort and
      chronic pain in the patients. In many cases, an additional surgical intervention
      is needed to remove the mesh. This study shows that mesenchymal stem cells and
      their exosomes, combined with a fibrin sealant, can be used for the successful
      fixation of these meshes. This new therapeutic approach, assayed in a murine
      model of incisional hernia, favors the modulation of the inflammatory response
      towards a less aggressive and pro-regenerative profile.

PMID- 29462709
TI  - Postinsertional Pain after Intrauterine Device Placement among Nulliparous
      Adolescents.
AB  - STUDY OBJECTIVE: To quantify the "normal" adolescent experience after
      intrauterine device insertion, to provide appropriate counseling for future
      adolescents. DESIGN: Prospective cohort study. SETTING: Marshall University
      Department of Obstetrics and Gynecology generalist and adolescent gynecology
      clinics. PARTICIPANTS: Nulliparous adolescents age 13-18 years and parous adults
      18 years of age or older who received a levonorgestrel intrauterine system (LNG
      IUS). INTERVENTIONS: Visual analogue scale (VAS) pain score and medication log
      was used for data collection for 2 weeks after LNG-IUS insertion. A separate
      chart review was completed for demographic factors and indications for procedure.
      MAIN OUTCOME MEASURES: VAS pain scores and medication use was compared between
      groups. RESULTS: Ninety-three subjects returned the VAS record and medication log
      (46 adolescents and 47 adults). There was no difference in the incidence of
      endometriosis or dysmenorrhea, but there was a higher prevalence of menorrhagia
      among adolescents (30/46, 65.2% vs 10/47, 21.3%; P < .001). Forty-five of forty
      seven (95.7%) adults vs 25/46 (54.3%) adolescents had contraception as an
      indication for intrauterine device use (P < .001). Pain scores were statistically
      higher among the adolescent group each day (P < .05) in the 2-week study period.
      The greatest mean differences occurred in the first 4 days. More adolescents
      (15/46, 32.6%) than adults (6/47, 12.8%) had a pain score greater than 5 during
      the first 3 days (P = .022). A statistical difference in amount of ibuprofen
      recorded was only noted on day 1 (P = .023) and day 4 (P = .046). CONCLUSION:
      Nulliparous adolescents who undergo LNG-IUS placement experience more
      postinsertional discomfort compared with parous adults; however, this method
      should still be considered first-line treatment in this age group.

PMID- 29462711
TI  - Exogenous mineralization of hard tissues using photo-absorptive minerals and
      femto-second lasers; the case of dental enamel.
AB  - : A radical new methodology for the exogenous mineralization of hard tissues is
      demonstrated in the context of laser-biomaterials interaction. The proposed
      approach is based on the use of femtosecond pulsed lasers (fs) and Fe3+-doped
      calcium phosphate minerals (specifically in this work fluorapatite powder
      containing Fe2O3 nanoparticles (NP)). A layer of the synthetic powder is applied
      to the surface of eroded bovine enamel and is irradiated with a fs laser (1040 nm
      wavelength, 1 GHz repetition rate, 150 fs pulse duration and 0.4 W average
      power). The Fe2O3 NPs absorb the light and may act as thermal antennae,
      dissipating energy to the vicinal mineral phase. Such a photothermal process
      triggers the sintering and densification of the surrounding calcium phosphate
      crystals thereby forming a new, dense layer of typically ~20 MUm in thickness,
      which is bonded to the underlying surface of the natural enamel. The dispersed
      iron oxide NPs, ensure the localization of temperature excursion, minimizing
      collateral thermal damage to the surrounding natural tissue during laser
      irradiation. Simulated brushing trials (pH cycle and mechanical force) on the
      synthetic layer show that the sintered material is more acid resistant than the
      natural mineral of enamel. Furthermore, nano-indentation confirms that the
      hardness and Young's modulus of the new layers are significantly more closely
      matched to enamel than current restorative materials used in clinical dentistry.
      Although the results presented herein are exemplified in the context of bovine
      enamel restoration, the methodology may be more widely applicable to human enamel
      and other hard-tissue regenerative engineering. STATEMENT OF SIGNIFICANCE: In
      this work we provide a new methodology for the mineralisation of dental hard
      tissues using femtosecond lasers and iron doped biomaterials. In particular, we
      demonstrate selective laser sintering of an iron doped fluorapatite on the
      surface of eroded enamel under low average power and mid-IR wavelength and the
      formation of a new layer to substitute the removed material. The new layer is
      evaluated through simulated brushing trials and nano-indentation. From the
      results we can conclude that is more acid resistant than natural enamel while,
      its mechanical properties are superior to that of current restorative materials.
      To the best of our knowledge this is the first time that someone demonstrated,
      laser sintering and bonding of calcium phosphate biomaterials on hard tissues.
      Although we here we discuss the case of dental enamel, similar approach can be
      adopted for other hard tissues, leading to new strategies for the fixation of
      bone/tooth defects.

PMID- 29462713
TI  - Which spike train distance is most suitable for distinguishing rate and temporal
      coding?
AB  - BACKGROUND: It is commonly assumed in neuronal coding that repeated presentations
      of a stimulus to a coding neuron elicit similar responses. One common way to
      assess similarity are spike train distances. These can be divided into spike
      resolved, such as the Victor-Purpura and the van Rossum distance, and time
      resolved, e.g. the ISI-, the SPIKE- and the RI-SPIKE-distance. NEW METHOD: We use
      independent steady-rate Poisson processes as surrogates for spike trains with
      fixed rate and no timing information to address two basic questions: How does the
      sensitivity of the different spike train distances to temporal coding depend on
      the rates of the two processes and how do the distances deal with very low rates?
      RESULTS: Spike-resolved distances always contain rate information even for
      parameters indicating time coding. This is an issue for reasonably high rates but
      beneficial for very low rates. In contrast, the operational range for detecting
      time coding of time-resolved distances is superior at normal rates, but these
      measures produce artefacts at very low rates. The RI-SPIKE-distance is the only
      measure that is sensitive to timing information only. COMPARISON WITH EXISTING
      METHODS: While our results on rate-dependent expectation values for the spike
      resolved distances agree with Chicharro et al. (2011), we here go one step
      further and specifically investigate applicability for very low rates.
      CONCLUSIONS: The most appropriate measure depends on the rates of the data being
      analysed. Accordingly, we summarize our results in one table that allows an easy
      selection of the preferred measure for any kind of data.

PMID- 29462712
TI  - Macrophage involvement affects matrix stiffness-related influences on cell
      osteogenesis under three-dimensional culture conditions.
AB  - : Accumulating evidence indicates that the physicochemical properties of
      biomaterials exert profound influences on stem cell fate decisions. However,
      matrix-based regulation selected through in vitro analyses based on a given cell
      population do not genuinely reflect the in vivo conditions, in which multiple
      cell types are involved and interact dynamically. This study constitutes the
      first investigation of how macrophages (Mphis) in stiffness-tunable
      transglutaminase cross-linked gelatin (TG-gel) affect the osteogenesis of bone
      marrow-derived mesenchymal stem cells (BMMSCs). When a single cell type was
      cultured, low-stiffness TG-gels promoted BMMSC proliferation, whereas high
      stiffness TG-gels supported cell osteogenic differentiation. However, Mphis in
      high-stiffness TG-gels were more likely to polarize toward the pro-inflammatory
      M1 phenotype. Using either conditioned medium (CM)-based incubation or Transwell
      based co-culture, we found that Mphis encapsulated in the low-stiffness matrix
      exerted a positive effect on the osteogenesis of co-cultured BMMSCs. Conversely,
      Mphis in high-stiffness TG-gels negatively affected cell osteogenic
      differentiation. When both cell types were cultured in the same TG-gel type and
      placed into the Transwell system, the stiffness-related influences of Mphis on
      BMMSCs were significantly altered; both the low- and high-stiffness matrix
      induced similar levels of BMMSC osteogenesis. Although the best material
      parameter for synergistically affecting Mphis and BMMSCs remains unknown, our
      data suggest that Mphi involvement in the co-culture system alters previously
      identified material-related influences on BMMSCs, such as matrix stiffness
      related effects, which were identified based on a culture system involving a
      single cell type. Such Mphi-stem cell interactions should be considered when
      establishing proper matrix parameter-associated cell regulation in the
      development of biomimetic biomaterials for regenerative applications. STATEMENT
      OF SIGNIFICANCE: The substrate stiffness of a scaffold plays critical roles in
      modulating both reparative cells, such as mesenchymal stem cells (MSCs), and
      immune cells, such as macrophages (Mphis). Although the influences of material
      stiffness on either Mphis or MSCs, have been extensively described, how the two
      cell types respond to matrix cues to dynamically affect each other in a three
      dimensional (3D) biosystem remains largely unknown. Here, we report our findings
      that, in a platform wherein Mphis and bone marrow-derived MSCs coexist, matrix
      stiffness can influence stem cell fate through both direct matrix-associated
      regulation and indirect Mphi-based modulation. Our data support future studies of
      the MSC-Mphi-matrix interplay in the 3D context to optimize matrix parameters for
      the development of the next biomaterial.

PMID- 29462714
TI  - Alterations of conjunctival glycocalyx and microcirculation in non-septic
      critically ill patients.
AB  - As of now the relationship between glycocalyx degradation and microcirculatory
      perfusion abnormalities in non-septic critical ill patients is unclear. In
      addition, conjunctival sidestream dark field-imaging for the purpose of
      glycocalyx thickness estimation has never been performed. We aimed to investigate
      whether changes in glycocalyx thickness in non-septic patients are associated
      with microcirculatory alterations in conjunctival and sublingual mucosa. In this
      single-centre prospective observational study, using techniques for direct in
      vivo observation of the microcirculation, we performed a single measurement of
      microcirculatory perfusion parameters and visualized glycocalyx thickness in both
      ocular conjunctiva and sublingual mucosa in mixed cardio surgical (n = 18) and
      neurocritical patients (n = 27) and compared these data with age-matched healthy
      controls (n = 20). In addition we measured systemic syndecan-1 levels. In the
      sublingual and conjunctival region we observed a significant increase of the
      perfused boundary region (PBR) in both neuro-critical and cardiac surgical ICU
      patients, compared to controls. There was a significant increase of syndecan-1 in
      ICU patients comparing with controls and in cardiac patients comparing with
      neurological (120.0[71.0-189.6] vs. 18.0[7.2-40.7], p < 0.05). We detected a weak
      correlation between syndecan-1 and sublingual PBR but no correlations between
      global glycocalyx damage and conjuctival glycocalyx thickness. We found
      significantly lower perfused vessel density (PVD) of small vessels in sublingual
      mucosa in patients after cardiac surgery in comparison with healthy subjects. In
      neuro-critical, but not cardiac surgery patients conjunctival TVD and PVD of
      small vessels were found to be significantly lower in comparison with controls.

PMID- 29462715
TI  - A new model of diabetic nephropathy in C57BL/6 mice challenged with advanced
      oxidation protein products.
AB  - There remains a lack of robust mouse models with key features of advanced human
      diabetic nephropathy (DN). Few options of murine models of DN require mutations
      to be superimposed to obtain desired phenotypic characteristics. Most genetically
      modified mice are on the C57BL/6 background; however, they are notorious for
      resistance to develop DN. To overcome these conundrums, this study reports a
      novel DN model by challenging with advanced oxidation protein products (AOPPs) in
      streptozotocin-induced diabetic C57BL/6 mice. AOPPs-challenged diabetic C57BL/6
      mice were more sensitive to develop progressive proteinuria, causing a 5.59-fold
      increase in urine albumin to creatinine ratio as compared to diabetic controls by
      24 weeks. Typical lesions were present as demonstrated by significant diffuse
      mesangial expansion, diffuse podocyte foot process effacement, increased
      glomerular basement membrane thickness, focal arteriolar hyalinosis,
      mesangiolysis, and mild interstitial fibrosis. These changes were alleviated by
      losartan treatment. Collectively, these results suggest that AOPPs can accelerate
      the progression of DN in the resistant C57BL/6 mouse strain. Our studies offer a
      novel model for studying the pathogenesis of DN that resembles human diabetic
      kidney disease. It also makes it possible to interrogate the role of specific
      genetic modifications and to evaluate novel therapeutics to treat DN in
      preclinical setting.

PMID- 29462716
TI  - Macrophage-derived superoxide production and antioxidant response following
      skeletal muscle injury.
AB  - Macrophages are key players of immunity that display different functions
      according to their activation states. In a regenerative context, pro-inflammatory
      macrophages (Ly6Cpos) are involved in the mounting of the inflammatory response
      whereas anti-inflammatory macrophages (Ly6Cneg) dampen the inflammation and
      promote tissue repair. Reactive oxygen species (ROS) production is a hallmark of
      tissue injury and of subsequent inflammation as described in a bacterial
      challenge context. However, whether macrophages produce ROS following a sterile
      tissue injury is uncertain. In this study, we used complementary in vitro, ex
      vivo and in vivo experiments in mouse to show that macrophages do not release ROS
      following a sterile injury in skeletal muscle. Furthermore, expression profiles
      of genes involved in the response to oxidative stress in Ly6Cpos and Ly6Cneg
      macrophage subsets did not indicate any antioxidant response in this context.
      Finally, in vivo, pharmacological antioxidant supplementation with N-Acetyl
      cysteine (NAC) following skeletal muscle injury did not alter macrophage
      phenotype during skeletal muscle regeneration. Overall, these results indicate
      that following a sterile injury, macrophage-derived ROS release is not involved
      in the regulation of the inflammatory response in the regenerating skeletal
      muscle.

PMID- 29462717
TI  - Evaluating the impact of diabetes and diabetic cardiomyopathy rat heart on the
      outcome of ischemia-reperfusion associated oxidative stress.
AB  - Earlier literature underlines that oxidative stress plays a major role in the
      pathology of myocardial ischemia-reperfusion (I/R) injury, diabetic
      cardiomyopathy (DCM), diabetes mellitus (DM), fibrosis and hypertrophy which
      could adversely affect the normal cardiac function. However, the contributory
      role of oxidative stress in I/R pathology of heart with pre-existing
      abnormalities or diseases like DM and DCM remains to be explored. I/R injury was
      induced in normal (normal diet), DM (normal diet + streptozotocin: multiple low
      dose of 30 mg/kg) and DCM (high fat diet (40% fat) + streptozotocin: multiple low
      dose of 30 mg/kg) rat hearts using Langendorff isolated heart perfusion
      apparatus. Cardiac physiological recovery after I/R was assessed by hemodynamic
      parameters like LVDP, and LVSP, whereas cardiac injury was measured by tissue
      infarct size, and apoptosis, LDH, and CK release in coronary effluent. The
      oxidative stress was evaluated in myocardial homogenate, mitochondrial
      subpopulation, and microsomes. Reperfusing the ischemic DCM heart significantly
      deteriorated cardiac physiological recovery and elevated the cardiac injury
      (infarct size: 60%), compared to the control. But in DM heart, physiological
      recovery was prominent in the initial phase of reperfusion but deteriorated
      towards the end of reperfusion, supported by less infarct size. In addition,
      elevated lipid peroxidation (70% in DCM-I/R vs Sham) and impaired antioxidant
      enzymes (% decline vs Sham: GSH - 56% (DM), 63% (DCM); Catalase - 58% (DM), 35%
      (DCM); GPx - 19% (DM), 27% (DCM) and GR - 28% (DCM)) was observed in myocardial
      tissue from both DM and DCM. Interestingly, upon reperfusion, only normal heart
      showed significant deterioration in the antioxidant defense system. Collectively
      these results demonstrated that I/R induced oxidative stress is minimal in DM and
      DCM rat heart, despite high infarct size and low cardiac performance. This may be
      due to the prior adaptive modification in the antioxidant system associated with
      disease pathology.

PMID- 29462718
TI  - Genetic diversity of the Plasmodium vivax phosphatidylinositol 3-kinase gene in
      two regions of the China-Myanmar border.
AB  - Artemisinin resistance in Plasmodium falciparum was associated with mutations in
      the propeller domain of the PfK13 gene and increased phosphatidylinositol-3'
      kinase (PfPI3K) activity. Assessment of the genetic diversity of the PfK13
      ortholog PvK12 in Plasmodium vivax field samples from the same hotspots of P.
      falciparum artemisinin resistance revealed a limited genetic diversity of PvK12.
      Following the same logic, we analyzed genetic variations of the PvPI3K gene in
      188 P. vivax field isolates from two geographic locations along the China-Myanmar
      border. Overall, high genetic diversity of PvPI3K was observed; parasites from
      Yunnan's Tengchong County had higher genetic diversity than those from Laiza
      Township, Kachin State, Myanmar. Almost all the neutrality tests applied detected
      statistically significant deviation from zero. The negative Tajima's D values in
      both populations implicated that PvPI3K gene might have experienced either a
      directional selection or an expansion in population size. There was low linkage
      disequilibrium between the PvPI3K mutations in both populations, suggesting the
      existence of large, almost panmictic, parasite populations that enabled effective
      recombination. This later result was confirmed by the detection of a minimum of
      five recombination events in each population with two major breakpoints. Multiple
      tests for selection confirmed a signature of purifying selection on PvPI3K. All
      the amino acid mutations were predicted to be neutral for the PI3K protein's
      function. These findings provide insights on the genetic diversity of P. vivax
      populations along the China-Myanmar border.

PMID- 29462719
TI  - Comparative genomics of Vibrio cholerae El Tor strains isolated at epidemic
      complications in Siberia and at the Far East.
AB  - The territory of Siberia and the Far East of Russia is classified as epidemically
      safe for cholera; however, in the 1970s and 1990s a number of infection
      importation cases and acute outbreaks associated with the cholera importation
      were reported. Here, we analyze genomes of four Vibrio cholerae El Tor strains
      isolated from humans during epidemic complications (imported cases, an outbreak)
      in the 1990s. The analyzed strains harbor the classical allele of the cholera
      toxin subunit B gene (ctxB1); thus, belong to genetically altered variants of the
      El Tor biotype. Analysis of the genomes revealed their high homology with the V.
      cholerae N16961 reference strain: 85-93 SNPs were identified in the core genome
      as compared to the reference. The determined features of SNPs in the CTX prophage
      made it possible to propose the presence of a new subtype - CTX-2a in two
      strains; the other two strains carried the prophage of CTX-3 type. Results of
      phylogenetic analysis based on SNP-typing demonstrated that two strains belonged
      to the second wave, and two - to the early third wave of cholera dissemination in
      the world. Phylogenetic reconstruction in combination with epidemiological data
      permitted to trace the origin of the strains and the way of their importation to
      the Russian Federation directly or through temporary cholera foci.

PMID- 29462720
TI  - Engineering Introns to Express RNA Guides for Cas9- and Cpf1-Mediated Multiplex
      Genome Editing.
AB  - The clustered regularly interspaced short palindromic repeat (CRISPR) system has
      emerged as the revolutionary platform for DNA targeting. This system uses a site
      specific RNA guide to direct a CRISPR effector (e.g., Cas9 and Cpf1) to a DNA
      target. Here, we elaborate a general strategy to simultaneously express multiple
      guide RNAs (gRNA) and CRISPR RNAs (crRNA) from introns of Cas9 and Cpf1. This
      method utilizes the endogenous tRNA processing system or crRNA processing
      activity of Cpf1 to cleave the spliced intron that contains tRNA-gRNA polycistron
      or crRNA-crRNA array. We demonstrated that the tRNA-gRNA intron is able to fuse
      with Cas9 as one gene. Such a hybrid gene could be expressed using one polymerase
      II promoter, and exhibited high efficiency and robustness in simultaneously
      targeting multiple sites. We also implemented this strategy in Cpf1-mediated
      genome editing using intronic tRNA-crRNA and crRNA-crRNA arrays. Interestingly,
      hybrid genes containing Cpf1 and intronic crRNA array exhibited remarkably
      increased efficiency compared with the conventional Cpf1 vectors. Taken together,
      this study presents a method to express CRISPR reagents from one hybrid gene to
      increase genome-editing efficiency and capacity. Owing to its simplicity and
      versatility, this method could be broadly used to develop sophisticated CRISPR
      tools in eukaryotes.

PMID- 29462721
TI  - miRNAs as a Secret Weapon in the Battlefield of Haustoria, the Interface between
      Parasites and Host Plants.

PMID- 29462722
TI  - Relationships between Gene Structure and Genome Instability in Flowering Plants.
AB  - Flowering plant (angiosperm) genomes are exceptional in their variability with
      respect to genome size, ploidy, chromosome number, gene content, and gene
      arrangement. Gene movement, although observed in some of the earliest plant
      genome comparisons, has been relatively underinvestigated. We present herein a
      description of several interesting properties of plant gene and genome structure
      that are pertinent to the successful movement of a gene to a new location. These
      considerations lead us to propose a model that can explain the frequent success
      of plant gene mobility, namely that Small Insulated Genes Move Around (SIGMAR).
      The SIGMAR model is then compared with known processes for gene mobilization, and
      predictions of the SIGMAR model are formulated to encourage future
      experimentation. The overall results indicate that the frequent gene movement in
      angiosperm genomes is partly an outcome of the unusual properties of angiosperm
      genes, especially their small size and insulation from epigenetic silencing.

PMID- 29462723
TI  - Comparison of two integration methods for dynamic causal modeling of
      electrophysiological data.
AB  - Dynamic causal modeling (DCM) is a methodological approach to study effective
      connectivity among brain regions. Based on a set of observations and a
      biophysical model of brain interactions, DCM uses a Bayesian framework to
      estimate the posterior distribution of the free parameters of the model (e.g.
      modulation of connectivity) and infer architectural properties of the most
      plausible model (i.e. model selection). When modeling electrophysiological event
      related responses, the estimation of the model relies on the integration of the
      system of delay differential equations (DDEs) that describe the dynamics of the
      system. In this technical note, we compared two numerical schemes for the
      integration of DDEs. The first, and standard, scheme approximates the DDEs (more
      precisely, the state of the system, with respect to conduction delays among brain
      regions) using ordinary differential equations (ODEs) and solves it with a fixed
      step size. The second scheme uses a dedicated DDEs solver with adaptive step
      sizes to control error, making it theoretically more accurate. To highlight the
      effects of the approximation used by the first integration scheme in regard to
      parameter estimation and Bayesian model selection, we performed simulations of
      local field potentials using first, a simple model comprising 2 regions and
      second, a more complex model comprising 6 regions. In these simulations, the
      second integration scheme served as the standard to which the first one was
      compared. Then, the performances of the two integration schemes were directly
      compared by fitting a public mismatch negativity EEG dataset with different
      models. The simulations revealed that the use of the standard DCM integration
      scheme was acceptable for Bayesian model selection but underestimated the
      connectivity parameters and did not allow an accurate estimation of conduction
      delays. Fitting to empirical data showed that the models systematically obtained
      an increased accuracy when using the second integration scheme. We conclude that
      inference on connectivity strength and delay based on DCM for EEG/MEG requires an
      accurate integration scheme.

PMID- 29462725
TI  - Superimposition of maximal stress and necrosis areas at the top of the femoral
      head in hip aseptic osteonecrosis.
AB  - INTRODUCTION: Recent reports described possible mechanical factors in the
      development and aggravation of osteonecrosis of the femoral head (OFH), but these
      have yet to be confirmed on dedicated mechanical study. We therefore developed a
      3D finite element model based on in-vivo data from patients with incipient OFH,
      with a view to determining whether the necrosis area was superimposed on the
      maximal stress area on the femoral head. HYPOTHESIS: The location of the necrosis
      area is determined by stress on the femoral head. MATERIAL AND METHOD: All
      patients from the rheumatology department with early stage OFH in our center were
      investigated. Analysis of CT scans showed stress distribution on the head by 3D
      finite elements models, enabling determination of necrosis volume within the
      maximal stress area and of the percentage intersection of necrosis within the
      stress area (%I n/s: necrosis volume in stress area divided by total stress area
      volume and multiplied by 100) and of stress within the necrosis area (%I s/n:
      stress volume in necrosis area divided by total necrosis area volume and
      multiplied by 100). RESULTS: Nineteen of the 161 patients assessed
      retrospectively for the period between 2006 and 2015 had incipient unilateral
      OFH, 10 of whom (4 right, 6 left) had CT scans of sufficient quality for
      inclusion. Mean age was 52 years (range, 37-81 years). Mean maximal stress was
      1.63MPa, mean maximal exported stress volume was 2,236.9 mm3 and mean necrosis
      volume 6,291.1 mm3. Mean %I n/s was 83% and mean %I s/n 35%, with no significant
      differences according to gender, age, side or stress volume. There was a strong
      inverse correlation between necrosis volume and %I s/n (R2=-0.92) and a strong
      direct correlation between exported stress volume and %I s/n (R2=0.55). %I s/n
      was greater in small necrosis (<7,000mm3). CONCLUSION: OFH seems to develop
      within the maximal stress area on the femoral head. The present results need
      confirmation by larger-scale studies. We consider it essential to take account of
      these mechanical parameters to reduce failure rates in conservative treatment of
      OFH. LEVEL OF EVIDENCE: IV. CASE SERIES: 

PMID- 29462726
TI  - Clinically-diagnosed Mediterranean Spotted Fever in Malta.
AB  - BACKGROUND: Mediterranean Spotted Fever (MSF) is a tick-borne zoonosis caused by
      Rickettsia conorii which is endemic in Malta, an island in the South
      Mediterranean that is a popular tourist destination. Diagnosis is frequently
      based on clinical manifestations as laboratory results are often limited to a
      retrospective diagnosis. We describe the clinical presentation, diagnosis and
      treatment of children <16 years who presented with MSF from 2011 to 2016. METHOD:
      The demographics, clinical findings, laboratory results, management and outcome
      of all children hospitalised with suspected MSF based on the presence of fever
      and an eschar, were retrieved from their case notes. RESULTS: Over the five-year
      study period six children, aged between 17 months and 15 years, were diagnosed
      with MSF. All children had contact with ticks and the majority presented in
      summer. Laboratory results were non-specific and included elevated inflammatory
      markers, lymphocytosis/lymphopenia and hyponatraemia. Serological and molecular
      techniques were used for diagnosis. Response to clarithromycin or doxycycline was
      immediate. CONCLUSION: MSF should be included in the differential diagnosis of
      fever, rash and an eschar in children who travel to Malta. Despite advances in
      molecular diagnostics, clinical diagnosis remains important in the management of
      children with suspected MSF.

PMID- 29462724
TI  - Maturation trajectories of cortical resting-state networks depend on the
      mediating frequency band.
AB  - The functional significance of resting state networks and their abnormal
      manifestations in psychiatric disorders are firmly established, as is the
      importance of the cortical rhythms in mediating these networks. Resting state
      networks are known to undergo substantial reorganization from childhood to
      adulthood, but whether distinct cortical rhythms, which are generated by
      separable neural mechanisms and are often manifested abnormally in psychiatric
      conditions, mediate maturation differentially, remains unknown. Using
      magnetoencephalography (MEG) to map frequency band specific maturation of resting
      state networks from age 7 to 29 in 162 participants (31 independent), we found
      significant changes with age in networks mediated by the beta (13-30 Hz) and
      gamma (31-80 Hz) bands. More specifically, gamma band mediated networks followed
      an expected asymptotic trajectory, but beta band mediated networks followed a
      linear trajectory. Network integration increased with age in gamma band mediated
      networks, while local segregation increased with age in beta band mediated
      networks. Spatially, the hubs that changed in importance with age in the beta
      band mediated networks had relatively little overlap with those that showed the
      greatest changes in the gamma band mediated networks. These findings are relevant
      for our understanding of the neural mechanisms of cortical maturation, in both
      typical and atypical development.

PMID- 29462727
TI  - Children's understanding of yesterday and tomorrow.
AB  - A picture-sentence matching task was used to investigate children's understanding
      of yesterday and tomorrow. In Experiment 1, 3- to 5-year-olds viewed two pictures
      of an object with a visible change of state (e.g., a carved pumpkin and an intact
      pumpkin) while listening to sentences referring to past or future actions ("I
      carved the pumpkin yesterday" or "I'm gonna carve the pumpkin tomorrow") and
      selected the matching picture. Children performed better with past tense
      sentences than with future tense sentences, and including tomorrow in future
      tense sentences increased accuracy. In the next two experiments, 4- and 5-year
      olds (Experiment 2) and adults (Experiment 3) completed the same task but with
      sentences containing conflicting temporal information ("I carved the pumpkin
      tomorrow"). Children tended to select pictures depicting the outcome of actions
      regardless of tense or temporal adverb, whereas adults' judgments were based on
      temporal adverbs. In Experiment 4, 3- to 5-year-olds completed tasks requiring
      either forward or backward temporal reasoning about sentences referring to
      before, after, yesterday, today, and tomorrow. Across sentence types, forward
      temporal reasoning was easier for children than backward temporal reasoning.
      Altogether, results indicated that children understand yesterday better than
      tomorrow due to the increased cognitive demands involved in reasoning about
      future events.

PMID- 29462728
TI  - Treatment of lumbar discitis using silicon nitride spinal spacers: A case series
      and literature review.
AB  - INTRODUCTION: Septic infection of a lumbar intervertebral disc is a serious
      disorder which is often difficult to diagnose and appropriately treat because of
      the rarity of the disease, the varied presentation of symptoms, and the frequency
      of low-back pain within the overall population. Its etiology can be pyogenic,
      granulomatous, fungal, or parasitic; its incidence is rising due to increased
      patient susceptibility and improved diagnostic tools. Conservative treatments
      involve antibiotics, physical therapy, and/or immobilization. More aggressive
      management requires discectomy, debridement, and spinal fusion in combination
      with local and systemic antibiotic administration. PRESENTATION OF CASES:
      Presented here are two case studies of lumbar pyogenic discitis associated with
      Escherichia coli and Candida albicans infections. Both required single-level
      anterior discectomy followed by spinal fusion using an antimicrobial silicon
      nitride (Si3N4) spacer for stabilization without instrumentation. Localized
      antibiotics were used for only one of the patients. Follow-up CT and MRI scans
      showed that the infections had been resolved with no recurrence of symptoms.
      DISCUSSION: Si3N4 is a relatively new spinal spacer material. It was utilized in
      these two cases because it reportedly provides a local environment which promotes
      rapid arthrodesis while resisting bacterial adhesion and biofilm formation. It is
      also highly compatible with X-ray, MRI, and CT imaging modalities. These
      properties were particularly attractive for these two cases given the patients'
      histories, presentation of symptoms, and the decision to forego instrumentation.
      CONCLUSION: The use of Si3N4 as an antimicrobial spacer may lead to improved
      outcomes for patients with pyogenic discitis of the lumbar spine.

PMID- 29462729
TI  - The Influence of Artificial Cervical Disc Prosthesis Height on the Cervical
      Biomechanics: A Finite Element Study.
AB  - OBJECTIVE: Artificial cervical disc replacement is expected to maintain normal
      cervical biomechanics. At present, the effect of the Prestige LP prosthesis
      height on cervical biomechanics has not been thoroughly studied. This finite
      element study of the cervical biomechanics aims to predict how the parameters,
      like range of motion (ROM), adjacent intradiscal pressure, facet joint force, and
      bone-implant interface stress, are affected by different heights of Prestige LP
      prostheses. METHODS: The finite element model of intact cervical spine (C3-C7)
      was obtained from our previous study, and the model was altered to implant
      Prestige LP prostheses at the C5-C6 level. The effects of the height of 5, 6, and
      7 mm prosthesis replacement on ROM, adjacent intradiscal pressure, facet joint
      force, as well as the distribution of bone-implant interface stress were
      examined. RESULTS: ROM, adjacent intradiscal pressure, and facet joint force
      increased with the prosthesis height, whereas ROM and facet joint force decreased
      at C5-C6. The maximal stress on the inferior surface of the prostheses was
      greater than that on the superior surface, and the stresses increased with the
      prosthesis height. The biomechanical changes were slightly affected by the height
      of 5 and 6 mm prostheses, but were strongly affected by the 7-mm prosthesis.
      CONCLUSIONS: An appropriate height of the Prestige LP prosthesis can preserve
      normal ROM, adjacent intradiscal pressure, and facet joint force. Prostheses with
      a height of >=2 mm than normal can lead to marked changes in the cervical
      biomechanics and bone-implant interface stress.

PMID- 29462730
TI  - Biomechanical Stability Afforded by Unilateral Versus Bilateral Pedicle Screw
      Fixation with and without Interbody Support Using Lateral Lumbar Interbody
      Fusion.
AB  - OBJECTIVE: To determine the stability of fusion constructs with unilateral
      pedicle screw (UPS) or bilateral pedicle screw (BPS) fixation with and without an
      interbody implant using the lateral lumbar interbody (LLIF) approach. METHODS:
      Standard nondestructive flexibility tests were performed on 13 cadaveric lumbar
      specimens to assess spinal stability of intact specimens and 5 configurations of
      posterior and interbody instrumentation. Spinal stability was determined as mean
      range of motion in flexion-extension, lateral bending, and axial rotation.
      Nonpaired comparisons were made for these 6 conditions: 1) intact; 2) unilateral
      interbody via the LLIF approach (LLIF construct); 3) unilateral interbody +
      unilateral pedicle screws (UPS) via the LLIF approach (LLIF + UPS); 4) unilateral
      interbody + bilateral pedicle screws (BPS) using the LLIF approach (LLIF+BPS); 5)
      UPS alone; and 6) BPS alone. RESULTS: UPS and BPS, with and without interbody
      support, significantly reduced range of motion during the majority of directions
      of loading. BPS alone provided greater stability than UPS alone and LLIF alone in
      all directions of motion except axial rotation. With interbody support, there was
      no significant difference in stability between BPS and UPS across all movement
      directions. CONCLUSIONS: These biomechanical results suggest that fixation in the
      lumbar spine with an interbody support using an LLIF approach with UPS is a
      promising alternative to BPS. Although BPS provides greater immediate stability
      compared with UPS, in the presence of a lateral interbody implant, UPS and BPS
      provide equivalent stability. In addition, LLIF does not appear to contribute
      significantly to immediate stability when BPS is used.

PMID- 29462731
TI  - Another Endovascular Therapy Strategy for Acute Tandem Occlusion: Protect-Expand
      Aspiration-Revascularization-Stent (PEARS) Technique.
AB  - OBJECTIVE: Initial stenotic occlusion of the internal carotid artery with
      intracranial artery occlusion in acute ischemic stroke is associated with high
      morbidity and can benefit from endovascular therapy. However, the optimal
      endovascular strategy is unclear. This study aimed to evaluate the feasibility of
      the "half" anterograde approach and clinical outcome of treated patients.
      Revascularization validity of the 2 "half" anterograde approach with (Protect
      Expand-Aspiration-Revascularization-Stent [PEARS] technique) or without (plain
      technique) using an embolic prevention device and aspiration was also compared.
      METHODS: Data on initial stenotic occlusion of the internal carotid artery with
      intracranial artery occlusion in our prospective stroke registry database between
      January 2015 and February 2017 were collected. Clinical and angiographic data
      were retrospectively analyzed. Clinical outcome was evaluated at 3 months,
      defined as a modified Rankin scale <=2 as a good clinical outcome. RESULTS:
      Overall, 26 patients with tandem occlusion were included; 96.3% of patients had
      successful recanalization. The rate of a good clinical outcome was 61.8%,
      symptomatic parenchymal hemorrhage was 7.7%, and mortality was 15.4%. The PEARS
      technique took less time (56 +/- 14 vs. 97 +/- 31 minutes; P = 0.002) and had
      less embolic events (0 vs. 30.8%; P = 0.012) compared with the plain technique.
      Use of the PEARS technique was an independent predictor for shortening
      revascularization time (beta = -0.651, P = 0.001). CONCLUSIONS: The half
      anterograde approach technique is feasible and safe for treating tandem
      occlusion. Furthermore, the PEARS technique is associated with a shorter
      reperfusion time and less embolic events than the plain technique, and should be
      recommended in tandem occlusion.

PMID- 29462732
TI  - Characteristics and Endovascular Management of the Posterior Cerebral Artery
      Anterior Temporal Branch Aneurysms.
AB  - PURPOSE: To investigate characteristics of the posterior cerebral artery anterior
      temporal branch aneurysm and the safety and efficacy of endovascular management.
      MATERIALS AND METHODS: A total of 6 patients with anterior temporal branch
      aneurysms were enrolled. All 6 patients had concurrent occlusion of the
      ipsilateral anterior circulating arteries. The aneurysms ranged from 2.5 to 5.0
      mm. All patients were treated and followed up. RESULTS: Four unruptured aneurysms
      were treated with coil embolization of the aneurysm sac only, with the parent
      artery maintained in 2 patients, slow flow in the parent artery in one and
      thrombosis at the aneurysm neck leading to parent artery occlusion in the last
      one. One patient with subarachnoid hemorrhage was treated with coil embolization
      of both the aneurysm and the parent artery, and the last patient with
      subarachnoid hemorrhage was treated with the Glubran 2 glue to embolize both the
      aneurysm and the parent artery. One patient with subarachnoid hemorrhage died of
      lung complication after embolization. Followed up for 3 months to 1 year, the 4
      patients with unruptured aneurysms had no symptoms, including 1 patient with slow
      flow in the anterior temporal artery and 1 patient with thrombosis and parent
      artery occlusion. The remaining patient with parent artery occlusion had a good
      recovery. CONCLUSIONS: The anterior temporal artery aneurysm is a special subtype
      of aneurysm and can be readily misdiagnosed as on the posterior cerebral artery
      trunk or the superior cerebellar artery. Endovascular management has a greater
      success rate, good effect, and fewer complications but with greater difficulties.

PMID- 29462733
TI  - The Effects of Intermittent Whole-Body Hypoxic Preconditioning on Patients with
      Carotid Artery Stenosis.
AB  - OBJECTIVE: To study the effects of intermittent whole-body hypoxic
      preconditioning on patients with carotid artery stenosis. METHODS: Fifty patients
      with carotid artery stenosis were selected and randomly divided into a hypoxic
      intervention group (HIG) and a control group (CG). Both groups were treated with
      a hypoxic respiration device for 7 days (HIG: 18% oxygen, CG: 21% oxygen). Venous
      blood samples were taken preoperatively and postoperatively. The subjects' vital
      signs were recorded during and after the intervention. After the completion of
      the trial, the concentrations of hemoglobin, hypoxia inducible factor-1alpha,
      erythropoietin, vascular endothelial growth factor, neuron-specific enolase,
      S100beta protein, brain-derived neurotrophic factor, serum aspartate
      transaminase, serum alanine aminotransferase, serum creatinine, and blood urea
      nitrogen were measured in the previously selected blood samples. RESULTS: During
      the intervention, the vital signs of the HIG were significantly different from
      those of the CG (P < 0.05). In the HIG, postoperative concentrations of
      hemoglobin, erythropoietin, hypoxia inducible factor-1alpha, and vascular
      endothelial growth factor were significantly more than the preoperative values (P
      < 0.05). In the CG, postoperative concentrations of neuron-specific enolase and
      S100beta protein were more than the preoperative values (P < 0.05). The
      concentrations of brain-derived neurotrophic factor, serum aspartate
      transaminase, serum alanine aminotransferase, serum creatinine, and blood urea
      nitrogen showed no significant differences between their preoperative and
      postoperative values in either the HIG or the CG (P > 0.05). CONCLUSIONS:
      Intermittent hypoxic preconditioning can change the vital signs and hematologic
      indexes of patients with carotid artery stenosis without causing new
      postoperative complications or organ damage.

PMID- 29462734
TI  - Divergent Bilateral Posterior Lumbar Interbody Fusion with Cortical Screw
      Fixation: Description of New Trajectory for Interbody Technique from Midline
      Exposure.
AB  - BACKGROUND: A major drawback to use of cortical bone trajectory pedicle screws
      (CBTPSs) with traditional posterior lumbar interbody fusion (PLIF) and
      transforaminal lumbar interbody fusion grafts is that traditional graft insertion
      trajectories require wider posterior exposure. This wider exposure, beyond the
      limits otherwise required for CBTPS placement, negates a primary benefit of CBTPS
      fixation. The aim of this study was to define an alternative surgical technique
      for interbody graft placement that, when used in conjunction with CBTPS fixation,
      permits both minimal soft tissue dissection and optimal graft placement. METHODS:
      A team of neurosurgeons specializing in treatment of spinal pathologies developed
      a surgical technique for insertion of bilateral PLIF grafts that complements the
      principles of CBTPS fixation. This technique is illustrated in a patient
      undergoing lumbosacral decompression, CBTPS fixation, and 3-column arthrodesis.
      RESULTS: The described technique uses a divergent trajectory of bilateral PLIF
      grafts rather than the traditional parallel or convergent trajectories.
      CONCLUSIONS: By aiming medially to laterally with the interbody graft, one
      recapitulates many advantages of CBTPSs, including avoidance of wide tissue
      dissection, greater intergraft volume available for bone grafting, and greater
      graft coverage of the hypophyseal ring. The prospective collection of outcome
      data for patients who undergo lumbosacral fusion using the divergent PLIF
      technique is ongoing.

PMID- 29462736
TI  - Use of a Pediatric Craniotome Drill for Cervical and Thoracic Spine
      Decompression: Safety and Efficacy.
AB  - BACKGROUND: Laminectomy, using a high-speed drill with an unprotected cutting
      drill bit, can be rapid and effective, but it has been associated with known
      complications. Another technique uses a pediatric craniotome drill with the
      footplate attachment. At present, there are no studies comparing clinical
      outcomes between these 2 stated decompressive techniques. METHODS: A
      retrospective review was conducted at a single institution. Two cohorts of
      patients were considered based on the technical method of laminectomy for
      decompression. One group had decompression with utilization of a high-speed
      drill, whereas the other group had decompression with a pediatric craniotome
      drill with a footplate attachment. The outcomes from each group were compared
      based on the length of operation, estimated blood loss, and associated
      complications. RESULTS: A total of 91 patients were included in the final
      analysis. Forty-five of the patients underwent laminectomy using a footplate and
      46, using a high-speed drill. The footplate group was associated with
      significantly shorter operative time (159 vs. 205 minutes; P = 0.008). In
      addition, the footplate technique demonstrated less estimated blood loss (254 vs.
      349 mL), and less incidence of durotomies (2.2% vs. 10.9%); however, neither of
      these 2 outcomes achieved statistical significance. CONCLUSIONS: Despite being an
      older technique, there was a shorter operative time in the footplate group
      without increased blood loss or incidence of durotomy. Although comparable
      results are operator dependent, this technique is a safe alternative for
      performing cervical and thoracic laminectomies.

PMID- 29462735
TI  - Anatomical Variations of Brain Venous Sinuses in Patients with Arteriovenous
      Malformations: Incidental Finding or Causative Factor?
AB  - OBJECTIVE: Acquired anomalies of the dural venous sinuses (DVS) have been
      correlated extensively with the development of dural arteriovenous fistulas
      (DAVFs). Despite the known similarities of DAVFs' pathogenesis with that of
      arteriovenous malformations (AVMs), the relationship of venous sinuses anomalies
      with AVMs scarcely has been studied. We aimed to investigate whether patients
      with AVM show a greater prevalence of congenital DVS anomalies. We hypothesized
      that these congenital anomalies trigger AVM development during early childhood
      just as acquired DVS anomalies trigger DAVFs formation during adulthood. METHODS:
      Angiographic anomalies of the brain venous sinuses were studied in a cohort of 45
      consecutive patients with AVM and compared with the angiographic; venous sinus
      anomalies of a control group formed by a second consecutive; series of 45
      patients with subarachnoid hemorrhage. RESULTS: Congenital anomalies of any DVS
      were more frequent in patients with AVM than in the control group (49.8% vs.
      22.2%; P = 0.015). Congenital abnormalities of the superior sagittal sinus not
      only were more frequent in patients with AVM (27% vs. 6.7%; P = 0.021) but seemed
      also related to the AVM location: in 5 of the 6 AVM cases with unilateral
      superior sagittal sinus aplasia, the AVM was ipsilateral to the venous anomaly.
      CONCLUSIONS: Patients with AVM have a greater likelihood of congenital anomalies
      of any DVS. These anomalies seem to be related also to the AVM location. These
      findings suggest that congenital anomalies of DVS may be related to the
      development of AVMs.

PMID- 29462738
TI  - Detecting dysplasia using white light endoscopy or chromoendoscopy in ulcerative
      colitis patients without primary sclerosing cholangitis: A systematic review and
      meta-analysis.
AB  - BACKGROUND: Endoscopic examinations are a vital diagnostic tool for dysplasia.
      Establishing the precision of different modes of examination is essential due to
      the disparate pick-up rates of dysplasia. OBJECTIVE: The aim of this article was
      to establish the pick-up rates of dysplastic or cancerous lesions using white
      light endoscopy (WLE) and random/targeted biopsies, or chromoendoscopy (CE), in
      patients with ulcerative colitis (UC) without primary sclerosing (PSC) or Crohn's
      disease (CD). DATA SOURCES: A systematic review to identify all studies up to
      November 2017, without language restriction, was conducted from PubMed, the
      Cochrane Controlled Trials Register (1960-2017), MEDLINE, CINAHL and EMBASE (1981
      2017). MeSH and text word terms used included "ulcerative colitis", "dysplasia",
      "random biopsy", "targeted biopsy", "colonoscopy", "white light", and
      "chromoendoscopy". Further searches were performed using the bibliographies of
      these articles. STUDY SELECTION: All studies reporting on colonoscopy detection
      rates of dysplasia and cancers in UC without involvement of PSC or CD were
      included. There was no age restriction to include patients. DATA EXTRACTION:
      Outcome data were extracted by 2 authors independently using outcome measures
      defined a priori. Quality assessment was performed using the Newcastle-Ottawa
      scales. DATA SYNTHESIS: Data were extracted and analysed according to meta
      analytical techniques using comprehensive meta-analysis. The pooled overall pick
      up rate of dysplastic/cancerous lesions on WLE random biopsies was 5.6% [Event
      rate 0.06 (0.01, 0.23), df = 4, I2 = 94%]. Using a combined random and targeted
      approach with WLE the incidence was 5.1% [Event rate 0.05 (0.03, 0.09), df = 4,
      I2 = 96%]. One study reported on CE and found a 7% pick-up rate for dysplastic
      lesions. CONCLUSIONS: Endoscopic examination of UC patients without PSC
      identifies dysplastic or cancerous lesions in 5-7% of cases. WLE and random
      biopsies may pick-up a similar number of lesions to targeted biopsies, however
      the number of biopsies may need to be greater to achieve this equivalence. CE has
      a slightly higher pick-up rate. Further comparative studies are required to
      strengthen the body of evidence.

PMID- 29462737
TI  - Pancreas-preserving management of grade-C pancreatic fistula and a novel bridging
      technique for repeat pancreaticojejunostomy: An observational study.
AB  - PURPOSE: Optimal surgical strategy for grade-C postoperative pancreatic fistula
      (POPF) after pancreaticoduodenectomy (PD) is not justified. External
      wirsungostomy is feasible. However, the subsequent repeat pancreaticojejunostomy
      (PJ) is challenging. This study aims to introduce our experience of external
      wirsungostomy for grade-C POPF and a novel technique to do the repeat PJ (re-PJ).
      MATERIALS AND METHODS: From January 1, 2012 to December 31, 2016, all consecutive
      patients who underwent pancreaticoduodenectomy (PD) with PJ were identified. The
      clinical data were retrospectively collected and analyzed. RESULTS: Out of 325
      patients, 11 patients (3.38%) underwent salvage re-laparotomy for grade-C POPF.
      External wirsungostomy was performed in 10 patients (3.08%). Four patients died
      of severe complications within 90 days postoperatively or tumor progression
      before the scheduled re-PJ was performed. Three patients got their external
      pancreatic drainage tube pulled out accidentally without causing severe
      consequences. Three patients underwent planned re-PJ after external
      wirsungostomy, including one with duct-to-mucosa PJ and two with the novel
      bridging technique. The operative times of the two patients undergoing the novel
      bridging technique were 120 min, 135 min, respectively, and the length of post
      operative hospital stay (LPHS) were 7 d, 5 d, respectively. The operative time
      and the LPHS of whom underwent duct-to-mucosa PJ were 315 min, 24 d,
      respectively. There was no major post-operative complication. CONCLUSION:
      External wirsungostomy may be a safe way to preserve the pancreas remnant in
      grade-C POPF patients. The novel bridging technique may be a simpler alternative
      to traditional PJ.

PMID- 29462739
TI  - Pre-surgery beliefs about pain and surgery as predictors of acute and chronic
      post-surgical pain: A prospective cohort study.
AB  - BACKGROUND: Chronic pain post-surgical pain (CPSP) is common and has far-reaching
      negative consequences for patients, yet relatively few studies have evaluated the
      impact of both deficit- and resource-based beliefs about pain and surgery on
      subjective intensities of acute and chronic post-surgical pain. To address this
      issue a prospective cohort study was performed. METHOD: 259 consecutive surgery
      patients from general surgery, gynecology, and thoracic departments completed a
      self-report battery of demographics, pain experiences, and psychological factors
      24 h before surgery (T1) and provided follow-up pain intensity ratings 48 h-72 h
      after surgery (T2), and at a 4-month follow-up (T3). RESULTS: In the hierarchical
      regression model for acute post-operative pain intensity, pre-surgery pain self
      efficacy beliefs made a significant unique contribution independent of all other
      pre-surgery and surgery-related factors (i.e., age, presence of pre-surgical
      pain, type of anesthesia, surgery duration). In the prediction model for
      intensity of chronic post-surgical pain, beliefs about long-term effects of
      surgery had a unique impact after controlling other significant pre-surgery and
      surgery influences (gender, education, surgery time). CONCLUSION: Results
      underscored the potential utility of considering specific pre-surgery pain- and
      surgery-related beliefs as factors that predict patient experiences of acute and
      chronic post-operative pain.

PMID- 29462740
TI  - Listening to the voice of children with developmental speech and language
      disorders using narrative inquiry: Methodological considerations.
AB  - There are policy and theoretical drivers for listening directly to children's
      perspectives. These perspectives can provide insights to children's experiences
      of their daily lives and ways in which they construct their multiple identities.
      Qualitative methodology is a useful research paradigm with regard to exploring
      children's experiences. However, listening to the perspectives of children with
      speech and language disorders is a relatively new field of research. Therefore,
      it is important that researchers share their experiences of using methods and
      reflect on the strengths and limitations of these methods. The authors have used
      narrative inquiry with children with speech and language disorders to explore
      ways in which these children make sense of their experiences and construct their
      identities. In this paper, the authors reflect on methodological considerations
      when using narrative inquiry with children with speech and language disorders.
      They critically discuss three methodological considerations: narrative inquiry as
      a methodological choice, methods for data generation, limitations, and rigour.

PMID- 29462741
TI  - Synchrotron-based X-ray fluorescence study of gold nanorods and skin elements
      distribution into excised human skin layers.
AB  - Understanding the distribution of nanoparticles in skin layers is fundamentally
      important and essential for developing nanoparticle-based dermal drug delivery
      systems. In the present study, we provide insights into the distribution of gold
      nanorods (GNRs) functionalized with hydrophobic or hydrophilic ligands in human
      skin layers using synchrotron X-ray fluorescence (SR-XRF) spectroscopy, confocal
      microscopy, and transmission electron microscopy. The results confirmed the
      important role that the surface chemistry of GNRs plays in their penetration into
      the skin; the GNRs coated with polyethylene glycol were distributed into the skin
      layers to a greater extent than the GNRs coated with hydrophobic polystyrene
      thiol. In addition, SR-XRF analysis revealed that the spatial distribution of
      endogenous elements (phosphorus and sulfur) in skin layers demonstrated a
      significant "anti-correlation" relationship with that of GNRs. These results
      suggest possible association (via adsorption) between the GNRs and these two
      elements localized in skin, which can be valuable for understanding the
      penetration mechanism of gold nanoparticles into the skin.

PMID- 29462743
TI  - Utility of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX
      1) in the postmortem diagnosis of ischemic heart disease.
AB  - PURPOSE: Ischemic heart disease (IHD) is a major cause of death in developed
      countries. Postmortem IHD diagnosis using biochemical markers is difficult
      because of the postmortem changes. In the present study, we investigated the
      utility of soluble lectin-like low-density lipoprotein receptor-1 (sLOX-1) in
      body fluids obtained from forensic autopsy cases. METHODS: We measured
      pericardial fluid, urine, and serum sLOX-1 levels; these samples were obtained
      from medicolegal autopsy cases (n = 149, postmortem interval <72 h), and the
      utility of these biomarkers postmortem acute IHD diagnosis was evaluated.
      RESULTS: The pericardial fluid and urine of patients with acute IHD had higher
      sLOX-1 levels (p < .05) compared to the controls. No significant differences were
      found between the sLOX-1 level and the degree of coronary atherosclerosis, body
      mass index, and postmortem interval. CONCLUSION: sLOX-1 levels in pericardial
      fluid and urine samples obtained postmortem are useful markers of acute IHD.

PMID- 29462742
TI  - Refractory status epilepticus: Impact of baseline comorbidity and usefulness of
      STESS and EMSE scoring systems in predicting mortality and functional outcome.
AB  - PURPOSE: Little has been published on the prognostic value of the Status
      Epilepticus Severity Score (STESS) or the Epidemiology-based Mortality score in
      Status Epilepticus (EMSE) in refractory status epilepticus (RSE). We sought to
      analyze the prognostic value of STESS and EMSE and the impact of baseline
      comorbidities in mortality and functional outcome in RSE. METHODS: We designed an
      observational retrospective study of patients diagnosed with RSE between August
      2013 and September 2017. For each patient, we analyzed prospectively recorded
      demographic, clinical, comorbidity, electroencephalographic, treatment, and
      hospital stay-related data and calculated STESS and EMSE. All variables were
      compared statistically between patients with good and poor functional outcome at
      discharge and between patients who died in hospital and those who were alive at
      discharge. RESULTS: Fourty-nine patients had RSE; 35.4% died in hospital and 88%
      showed functional decline at discharge. Mortality was associated with baseline
      chronic kidney disease (CKD) (OR 19.25, p = 0.006), baseline modified Rankin
      scale score (mRS) (OR 3.38, p = 0.005), non-convulsive status epilepticus (NCSE)
      with coma (OR 11.9, p = 0.04), STESS (OR 2, p = 0.04), and EMSE (OR 1.3, p =
      0.02). Functional outcome was associated with baseline mRS (OR 13.9, p = 0.02),
      and EMSE (OR 1.3, p = 0.02). The optimal cutoff scores for predicting mortality
      were 4 for STESS and 60 for EMSE. EMSE predicted functional outcome with an
      optimal cutoff of 40. CONCLUSIONS: CKD, NCSE with coma and STESS were associated
      with mortality. mRS and EMSE were associated with mortality and functional
      outcome. EMSE was useful for predicting functional outcome, while EMSE and STESS
      were useful for predicting in-hospital mortality.

PMID- 29462744
TI  - Eye injuries from electrical weapon probes: Incidents, prevalence, and legal
      implications.
AB  - PURPOSE: While generally reducing morbidity and mortality, electrical weapons
      have risks associated with their usage, including burn injuries and trauma
      associated with uncontrolled fall impacts. However, the prevalence of significant
      eye injury has not been investigated. METHODS: We searched for incidents of
      penetrating eye injury from TASER(r) conducted electrical weapon (CEW) probes via
      open source media, litigation filings, and a survey of CEW law-enforcement master
      instructors. RESULTS: We report 20 previously-unpublished cases of penetrating
      eye injury from electrical weapon probes in law-enforcement field uses. Together
      with the 8 previously published cases, there are a total of 28 cases out of 3.44
      million field uses, giving a demonstrated CEW field-use risk of penetrating eye
      injury of approximately 1:123 000. Confidence limits [85 000, 178 000] by Wilson
      score interval. There have been 18 cases of total unilateral blindness or
      enucleation. We also present legal decisions on this topic. CONCLUSIONS: The use
      of electrical weapons presents a rare but real risk of total or partial
      unilateral blindness from electrical weapon probes. Catastrophic eye injuries
      appear to be the dominant non-fatal complication of electronic control.

PMID- 29462746
TI  - Developmental changes in infants' and mothers' pathways to achieving joint
      attention episodes.
AB  - Combining the joint attention approaches of Mundy and colleagues' (2007)
      experimental coding of infants' specific initiating and responding acts and of
      Bakeman and Adamson's (1986) descriptions of both infants' and mothers' behaviors
      during joint engagement, this study examined 29 infants' and mothers' initiatives
      and responses leading to success in achieving joint attention (JA) episodes
      during naturalistic interactions when infants were 13 and 17 months old. Analyses
      revealed developmental changes in initiative frequencies and in the origins of JA
      episodes. At 13 months, although infants' less sophisticated object-only
      initiatives (IObj) were most frequent, JA episodes most often originated in
      maternal combined initiatives (IJA), which focused on both object and partner. By
      17 months, however, infants' combined initiatives were most frequent and led to
      more JA episodes than any other initiative type. Infants with more combined
      initiatives achieved more JA episodes at both ages and greater 17-month
      vocabularies.

PMID- 29462745
TI  - Physiological and molecular mechanism of defense in cotton against Verticillium
      dahliae.
AB  - Cotton, a natural fiber producing crop of huge importance for textile industry,
      has been reckoned as the backbone in the economy of many developing countries.
      Verticillium wilt caused by Verticillium dahliae reflected as the most
      devastating disease of cotton crop in several parts of the world. Average losses
      due to attack of this disease are tremendous every year. There is urgent need to
      develop strategies for effective control of this disease. In the last decade,
      progress has been made to understand the interaction between cotton-V. dahliae
      and several growth and pathogenicity related genes were identified. Still, most
      of the molecular components and mechanisms of cotton defense against Verticillium
      wilt are poorly understood. However, from existing knowledge, it is perceived
      that cotton defense mechanism primarily depends on the pre-formed defense
      structures including thick cuticle, synthesis of phenolic compounds and delaying
      or hindering the expansion of the invader through advanced measures such as
      reinforcement of cell wall structure, accumulation of reactive oxygen species
      (ROS), release of phytoalexins, the hypersensitive response and the development
      of broad spectrum resistance named as, systemic acquired resistance (SAR).
      Investigation of these defense tactics provide valuable information about the
      improvement of cotton breeding strategies for the development of durable, cost
      effective, and broad spectrum resistant varieties. Consequently, this management
      approach will help to reduce the use of fungicides and also minimize other
      environmental hazards. In the present paper, we summarized the V. dahliae
      virulence mechanism and comprehensively discussed the cotton molecular mechanisms
      of defense such as physiological, biochemical responses with the addition of
      signaling pathways that are implicated towards attaining resistance against
      Verticillium wilt.

PMID- 29462747
TI  - Involvement of a newly identified atypical type II crustin (SpCrus5) in the
      antibacterial immunity of mud crab Scylla paramamosain.
AB  - Crustins, the main AMP family in Crustacea, are generated as isoforms in many
      species and implicated in innate immune responses, but their detailed molecular
      mechanisms on susceptible bacteria remain largely unclear. Type II and type I
      crustins are distinguished by glycine-rich region (GRR), which is a major marker
      motif, and some type II crustins exhibit stronger antibacterial activities than
      their GRR deletion mutants. In the present study, a novel crustin, namely,
      SpCrus5, was functionally characterized from a commercially valuable crab Scylla
      paramamosain. SpCrus5 contained a typical cysteine-rich domain at the N-terminus,
      a conserved WAP domain in the center, and a special GRR at the C-terminus, which
      is located in a site that differs from that of GRRs in typical type II crustins
      found between signal peptides and cysteine-rich domains. SpCrus5 shared high
      similarities with most type II crustins, and it was more closely related to type
      II crustins than to other retrieved crustins. SpCrus5 was predominantly expressed
      in gills and remarkably upregulated after the crabs were challenged with Vibrio
      parahemolyticus or Staphylococcus aureus, suggesting that SpCrus5 might
      participate in antibacterial immune responses. To further elucidate how this C
      terminal GRR affects the function of SpCrus5, we harvested a GRR deletion mutant
      (SpCrus5-DeltaGRR) by deleting the GRR. Liquid growth inhibition assays
      demonstrated that the antimicrobial activity of SpCrus5 was stronger than that of
      SpCrus5-DeltaGRR, and the antibacterial spectrum of the former toward Gram
      negative bacteria was broader than that of the latter. Binding assays revealed
      that the microorganism-binding ability and polysaccharide-binding activity of
      SpCrus5 were stronger than those of SpCrus5-DeltaGRR. SpCrus5 or SpCrus5-DeltaGRR
      agglutinated all tested Gram-positive bacteria. Therefore, the antibacterial
      activities of SpCrus5 were stronger and broader than those of SpCrus5-DeltaGRR,
      and the binding ability and agglutination activity might contribute to the
      antimicrobial activity of SpCrus5. These results revealed that the C-terminal GRR
      was necessary to produce an efficient antibacterial activity of SpCrus5. SpCrus5
      was highly identical with most type II crustins and it functioned as many type II
      crustins did, indicating that SpCrus5 was more likely an atypical type II crustin
      than a type I crustin. This study revealed that SpCrus5 participated as an
      essential antimicrobial effector in immune responses and provided new insights
      into the underlying mechanisms of the sequence and function diversity of
      crustins.

PMID- 29462748
TI  - Dietary administration effects of fenugreek seeds on skin mucosal antioxidant and
      immunity status of gilthead seabream (Sparus aurata L.).
AB  - Improving fish defense through the preventive administration of immunostimulants
      has an important role in controlling the outbreak of the disease in aquaculture.
      As a continuity of our previous studies, this paper describes the effects of
      dietary fenugreek (Trigonella foenum graecum) seeds on the skin mucosal
      antioxidant status and immune response of gilthead seabream (Sparus aurata L.).
      Fish were fed with four experimental diets: one a basal diet (control) and three
      diets with powdered fenugreek seeds incorporated in the fish feed at 1%, 5%, and
      10%. After eight weeks of feeding, free radicals scavenging and antioxidant
      assays were assessed in skin mucus by measuring the peroxidation of phospholipid
      liposomes, hydroxyl radical and hydrogen peroxide scavenging, measurement of
      total antioxidant activity and the determination of antioxidant activity in a
      linoleic acid system. The skin mucosal immune response was evaluated by measuring
      the IgM levels and some enzymatic activities (peroxidase, antiprotease, protease,
      esterase, and ceruloplasmin). Our results demonstrated that fenugreek inclusion
      improved the hydroxyl radical scavenging capacity and conferred very high
      antioxidant activity. Besides, only the highest supplementation level (10%) was
      able to augment the peroxidase and protease activities confronted by a general
      decrement in the antiprotease activity in the experimental fed groups with 1% and
      10%. These results suggest that the dietary administration of fenugreek at the
      higher inclusion dose enhances the skin mucosal immunity response and the
      antioxidant status of gilthead seabream a species with one of the highest rates
      of production in marine aquaculture.

PMID- 29462749
TI  - Effects of a probiotic (Bacillus licheniformis) on the growth, immunity, and
      disease resistance of Haliotis discus hannai Ino.
AB  - To study the effects of a probiotic (Bacillus lincheniformis) on the survival and
      growth of Haliotis discus hannai Ino, the expression levels of nonspecific immune
      genes and the resistance to Vibrio parahaemolyticus infection were assessed.
      Abalones (shell length: 27.64 +/- 1.59 mm, body weight: 4.17 +/- 0.32 g) were
      selected for use in an 8-week culture experiment and a 2-week V. parahaemolyticus
      artificial infection experiment. In both experiments, the control group (C) was
      fed with a basal feed and the experimental groups were fed with experimental food
      prepared by spraying the probiotic on the basal feed at different concentrations:
      103 (B1), 105 (B2), and 107 (B3) cfu/mL. The survival rate, total number of blood
      lymphocytes, activity of acid phosphatase, and expression level of heat shock
      protein 70 were significantly higher in B1, B2, and B3 than in C (P < 0.05). The
      specific growth rate of shell length, food intake, food conversion rate,
      phagocytic activity of blood lymphocytes, activities of myeloperoxidase and
      catalase (CAT), and expression levels of CAT and thioredoxin peroxidase of
      abalones in B2 were significantly higher than those in B1 and C (P < 0.05).
      Although the level of O2- produced by the respiratory burst of blood lymphocytes
      in B2 was not significantly different from those in B1 and B3, they were
      significantly higher than that in C (P < 0.05). The activity of superoxide
      dismutase (SOD), the nitric oxide levels produced by the respiratory burst of
      blood lymphocytes, and the expression levels of Mn-SOD in B1 and B3 were
      significantly higher than those in C but significantly lower than those in B2 (P
      < 0.05). Fourteen days after infection with V. parahaemolyticus, the cumulative
      mortality of abalones in B2 was significantly lower than those in B1 and C (P <
      0.05). These results indicate that the food containing 105 cfu/mL Bacillus
      licheniformis promoted food intake and growth of abalones and also improved their
      resistance to V. parahaemolyticus infection. Thus, B. licheniformis is a good
      potential probiotic.

PMID- 29462750
TI  - Personal exposure to fine particles (PM2.5) and respiratory inflammation of
      common residents in Hong Kong.
AB  - BACKGROUND: Given the lack of research on the personal exposure to fine particles
      (PM2.5) in Hong Kong, we examined the association between short-term personal
      exposure to PM2.5 and their constituents and inflammation in exhaled breath in a
      sample of healthy adult residents. METHOD: Forty-six participants underwent
      personal PM2.5 monitoring for averagely 6 days to obtain 276 samples. Fractional
      exhaled nitric oxide (FeNO), a biomarker of inflammation in exhaled breath, was
      measured at the end of each 24-h personal monitoring. PM2.5 chemical
      constituents, including organic carbon, elemental carbon, 16 polycyclic aromatic
      hydrocarbons (PAHs), and 6 phthalate esters, were speciated from the personal
      samples collected. A mixed-effects model was used to estimate the association of
      PM2.5 and their constituents with FeNO. The comparison was also made with
      parallel analyses using ambient concentrations. RESULTS: Personal exposures to
      PM2.5 (28.1 +/- 23.3 MUg/m3) were higher than the ambient levels (13.3 +/- 6.4
      MUg/m3) monitored by stations. The composition profile and personal-to-ambient
      concentration ratio varied among subjects with different occupations. An
      interquartile range (IQR) change in personal exposure to PM2.5 was positively
      associated with 12.8% increase in FeNO (95% confidence interval, CI: 5.5-20.7%),
      while nil association was found for ambient PM2.5. Among the constituents
      measured, only the carcinogenic PAHs were significantly associated with 12%
      increase in FeNO responses (95% CI, 0.0-25.6%). CONCLUSION: In conclusion, our
      study provides the first understanding about personal exposure to PM2.5 and
      possible sources in Hong Kong. The results also showed that personal exposure to
      PM2.5 and c-PAHs were linked to increased FeNO levels among healthy adults.

PMID- 29462751
TI  - Primary splenic malignant lymphoma mimicking metastasis of rectosigmoid cancer: A
      case report.
AB  - INTRODUCTION: Primary splenic malignant lymphoma is quite a rare disease, and its
      preoperative diagnosis is difficult. CASE PRESENTATION: An 80-year-old man was
      diagnosed with advanced rectosigmoid cancer with liver and splenic metastases,
      for which he underwent single-incision laparoscopic high anterior resection for
      the primary rectosigmoid cancer. After chemotherapy, he underwent laparoscopy
      assisted splenectomy and open partial hepatectomy of segment 3 and segment 5/6 of
      the liver. The resected specimen of the spleen showed primary splenic malignant
      lymphoma. DISCUSSION: A diagnosis of primary splenic malignant lymphoma seems to
      be made only occasionally at splenectomy. Patients with primary splenic malignant
      lymphoma treated by curative resection at an early clinical stage have a more
      favorable prognosis. Laparoscopy-assisted splenectomy is useful for reducing
      surgical invasiveness. CONCLUSION: Primary splenic malignant lymphoma should be
      included among the differential diagnoses of splenic tumors in patients with
      colorectal cancer with multiple metastases. Curative resection might be a
      therapeutic option for the treatment of primary splenic malignant lymphoma.
      Laparoscopy-assisted splenectomy is a useful strategy for reducing surgical
      invasiveness.

PMID- 29462752
TI  - A rare case report of a typical variant ossifying fibromyxoid tumor (OFMT),
      located in the retroauricular perimastoid region.
AB  - INTRODUCTION: Ossifying fibromixoid tumor of soft parts (OFMT) is a rare soft
      tissue and bone tumor. In its classic form, is considered benign, nevertheless
      aggressive clinical behaviour tumors with a different cytoarchitectural features
      of a malignant variant, have been described.The classification contains
      "typical", "atypical" and "malignant" variants. METHODS: A CT ear scan without
      contrast enhancement was carried out (October 2015), with coronal, sagittal and
      3D reconstructions. It was decided the removal of the neoformation with a simple
      dissection. RESULTS: In this report, we present a case of a typical variant OFMT
      localized in the retroauricular perimastoid region, with mastoid bone cortex not
      involved. CONCLUSIONS: Considering the extreme rarity of this "enigmatic" tumor
      which displays an uncertain line of differentiation, renders the differential
      diagnosis a true challenge.

PMID- 29462753
TI  - Paracecal hernia with intestinal ischemia treated with laparoscopic assisted
      surgery.
AB  - INTRODUCTION: Paracecal hernia is rare, and strangulation with ischemia has been
      infrequently observed in the limited number of published reports on paracecal
      hernias. PRESENTATION OF CASE: We describe a case of an incarcerated paracecal
      hernia with resultant ischemic bowel that was successfully treated with
      laparoscopic-assisted surgery. A 54-year-old man who had not undergone any
      surgery previously presented to our hospital with abdominal pain and vomiting. An
      abdominal computed tomographic scan showed evidence of an intestinal obstruction
      at a paracecal site. An emergency laparoscopic surgery demonstrated incarceration
      of a loop of the small bowel in the paracecal fossa. We removed the incarcerated
      small bowel from the paracecal fossa, noted that the tissue was necrotic, and
      resected this segment of bowel through a mini-laparotomy incision. The patient
      was discharged on the 13th postoperative day. DISCUSSION AND CONCLUSION: This
      case is unique in that the patient presented with small bowel strangulation,
      causing intestinal ischemia. Laparoscopic surgery is useful in the diagnosis of
      internal hernias and is also useful for the treatment of small bowel obstruction
      due to paracecal hernias complicated by ischemic bowel.

PMID- 29462754
TI  - A case of separation surgery with drainage tube-less (DRESS) esophagostomy for
      advanced cancer with a respiratory fistula.
AB  - INTRODUCTION: An esophagorespiratory fistula (ERF) can cause severe pneumonia or
      a lung abscess which progresses to life-threatening sepsis. A case of a patient
      with esophageal cancer and an esophagopulmonary fistula (EPF) who underwent
      separation surgery with drainage tube-less (DRESS) esophagostomy and was promptly
      started on definitive chemoradiotherapy (CRT) is reported. PRESENTATION OF CASE:
      A 79-year-old man visited a clinic with a month-long history of dysphagia.
      Esophageal cancer at the middle thoracic esophagus was detected, and invasion of
      the left main bronchus and lower lobe of the right lung was seen on contrast
      enhanced computed tomography (CT). Three weeks later, the patient was transferred
      to our hospital. CT showed a lung abscess in the lower lobe of the right lung
      that continued into the adjacent esophageal cancer. Due to the EPF, the patient
      underwent emergency surgery that consisted of esophageal separation surgery and
      double bilateral esophagostomy and enterostomy. Definitive CRT for the esophageal
      cancer was started from postoperative day 25. At six-month follow-up, the patient
      achieved relapse-free survival. DISCUSSION: Separation surgery with a DRESS
      esophagostomy provides good control of inflammation because of division of the
      respiratory tract from the alimentary tract, which allows prompt initiation of
      CRT. Alternatively, a DRESS esophagostomy allows patients to be free from any
      tube trouble. CONCLUSION: Separation surgery with a DRESS esophagostomy for an
      ERF is a promising method to improve patient quality of life that is less
      invasive, controls inflammation, and facilitates subsequent definitive CRT.

PMID- 29462757
TI  - Unveiling the pH dependent interaction between bolaamphiphiles (dicarboxylic
      acids) and C10TAB (decyltrimethylammonium bromide) in aqueous medium.
AB  - Development of stable self-assembled nanostructures (especially vesicles and
      liposomes), and understanding their physicochemical behaviors in aqueous solution
      is a long-standing topic of interest in chemical and biochemical research. In
      this progressive area, we report for the first-time formation of mixed micelles
      (at pH 12), and vesicles of anionic bolaamphiphiles (dicarboxylic acids viz.
      [Formula: see text] , with moderate values of n 10, 11, 12, and 14) in
      combination with a cationic surfactant decyltrimethylammonium bromide (C10TAB) in
      buffered aqueous medium at different pH (6.0, 6.5, 6.8, and 8.0 for bola 10, 11,
      12, and 14, respectively). Three pH dependent states of the solutions are
      observed: clear (high pH > 8), turbid and translucent (mid pH ~ 6-8), and viscous
      inhomogeneous oil-like state (low pH < 6). The micelle size varies from 6.24 to
      7.43 nm at pH 12, for vesicles the values are large (220-296 nm), and small (~30
      70 nm) in the pH range of 6.0-8.0. The self-assembly formation properties of
      their mixtures are herein investigated using different techniques viz. UV-vis
      spectroscopy, fluorescence spectroscopy, dynamic light scattering, laser confocal
      scanning microscopy, and isothermal titration calorimetry. The formed vesicles
      are fairly polydisperse, and show overall spherical shape. Formation of the
      bilayer assemblies, and their conversion to mixed micelles by the temperature
      effect are observed from steady state fluorescence anisotropy measurements.
      Micellization of the mixed bola-C10TAB species is endothermic and fairly entropy
      controlled; their formation/deformation is pH sensitive. They have spherical
      morphologies, and once formed at the right pH they are found to be very stable in
      terms of time. Thus, these vesicles have prospects for encapsulation and delivery
      of materials like drugs, and other substrates by controling the acid-base
      conditions of the system environment. The formed mixed micelles, and vesicles are
      expected to be low toxic, and thus green materials in nature with wider
      application possibilites.

PMID- 29462756
TI  - BAG3 Overexpression and Cytoprotective Autophagy Mediate Apoptosis Resistance in
      Chemoresistant Breast Cancer Cells.
AB  - Target-specific treatment modalities are currently not available for triple
      negative breast cancer (TNBC), and acquired chemotherapy resistance is a primary
      obstacle for the treatment of these tumors. Here we employed derivatives of BT
      549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of
      either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular
      pathways involved in the adaptation to drug-induced cell killing. All six drug
      adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to
      chemotherapy and decreased apoptosis sensitivity. Expression of the anti
      apoptotic co-chaperone BAG3 was notably enhanced in two thirds (4/6) of the six
      resistant lines simultaneously with higher expression of HSP70 in comparison to
      parental controls. Doxorubicin-resistant BT-549 (BT-549rDOX20) and 5-Fluorouracil
      resistant MDA-MB-468 (MDA-MB-468r5-FU2000) cells were chosen for further analysis
      with the autophagy inhibitor Bafilomycin A1 and lentiviral depletion of ATG5,
      indicating that enhanced cytoprotective autophagy partially contributes to
      increased drug resistance and cell survival. Stable lentiviral BAG3 depletion was
      associated with a robust down-regulation of Mcl-1, Bcl-2 and Bcl-xL, restoration
      of drug-induced apoptosis and reduced cell adhesion in these cells, and these
      death-sensitizing effects could be mimicked with the BAG3/Hsp70 interaction
      inhibitor YM-1 and by KRIBB11, a selective transcriptional inhibitor of HSF-1.
      Furthermore, BAG3 depletion was able to revert the EMT-like transcriptional
      changes observed in BT-549rDOX20 and MDA-MB-468r5-FU2000 cells. In summary,
      genetic and pharmacological interference with BAG3 is capable to resensitize TNBC
      cells to treatment, underscoring its relevance for cell death resistance and as a
      target to overcome therapy resistance of breast cancer.

PMID- 29462758
TI  - Layer - Structured partially reduced graphene oxide sheathed mesoporous MoS2
      particles for energy storage applications.
AB  - Mesoporous architectures are remarkable electrode materials for energy storage
      system due to their large number of active sites and high surface area. Here we
      report, mesoporous MoS2 particles (pore diameter 34.04 nm) well attached to the
      surface of thin layered reduced graphene oxide (rGO) via an ultrasonic chemical
      method for supercapacitor applications. The rGO not only increases the
      conductivity of MoS2 but also provides a substrate for the attachment of MoS2
      with low aggregation. The porous MoS2 provides a large surface area and
      sufficient way for the fast transport of electrolyte ions toward electrode
      materials. As a result, the synthesized MoS2/rGO composites exhibited excellent
      electrochemical performance with a specific capacitance 314.5 F/g in 2M KOH
      aqueous solution at a scan rate of 10 mV/s and excellent specific capacitance
      retention (80.02%) after 1000 cycles in a three electrode system for energy
      storage applications.

PMID- 29462755
TI  - The human T-cell leukemia virus type-1 p30II protein activates p53 and induces
      the TIGAR and suppresses oncogene-induced oxidative stress during viral
      carcinogenesis.
AB  - In normal cells, aberrant oncogene expression leads to the accumulation of
      cytotoxic metabolites, including reactive oxygen species (ROS), which can cause
      oxidative DNA-damage and apoptosis as an intrinsic barrier against neoplastic
      disease. The c-Myc oncoprotein is overexpressed in many lymphoid cancers due to c
      myc gene amplification and/or 8q24 chromosomal translocations. Intriguingly, p53
      is a downstream target of c-Myc and hematological malignancies, such as adult T
      cell leukemia/lymphoma (ATL), frequently contain wildtype p53 and c-Myc
      overexpression. We therefore hypothesized that p53-regulated pro-survival signals
      may thwart the cell's metabolic anticancer defenses to support oncogene
      activation in lymphoid cancers. Here we show that the Tp53-induced glycolysis and
      apoptosis regulator (TIGAR) promotes c-myc oncogene-activation by the human T
      cell leukemia virus type-1 (HTLV-1) latency-maintenance factor p30II, associated
      with c-Myc deregulation in ATL clinical isolates. TIGAR prevents the
      intracellular accumulation of c-Myc-induced ROS and inhibits oncogene-induced
      cellular senescence in ATL, acute lymphoblastic leukemia, and multiple myeloma
      cells with elevated c-Myc expression. Our results allude to a pivotal role for
      p53-regulated antioxidant signals as mediators of c-Myc oncogenic functions in
      viral and non-viral lymphoid tumors.

PMID- 29462759
TI  - Associations and predictions of readmission or death in acutely admitted older
      medical patients using self-reported frailty and functional measures. A Danish
      cohort study.
AB  - OBJECTIVE: To assess whether frailty in acutely admitted older medical patients,
      assessed by a self-report questionnaire and evaluation of functional level at
      discharge, was associated with readmission or death within 6 months after
      discharge. A second objective was to assess the predictive performance of models
      including frailty, functional level, and known risk factors. METHODS: A cohort
      study including acutely admitted older patients 65+ from seven medical and two
      acute medical units. The Tilburg Frailty Indicator (TFI), Timed-Up-and-Go (TUG),
      and grip strength (GS) exposure variables were measured. Associations were
      assessed using Cox regression with first unplanned readmission or death (all
      causes) as the outcome. Prediction models including the three exposure variables
      and known risk factors were modelled using logistic regression and C-statistics.
      RESULTS: Of 1328 included patients, 50% were readmitted or died within 6 months.
      When adjusted for gender and age, there was an 88% higher risk of readmission or
      death if the TFI scores were 8-13 points compared to 0-1 points (HR 1.88, CI
      1.38;2.58). Likewise, higher TUG and lower GS scores were associated with higher
      risk of readmission or death. The area under the curve for the prediction models
      ranged from 0.64 (0.60;0.68) to 0.72 (0.68;0.76). CONCLUSION: In acutely admitted
      older medical patients, higher frailty assessed by TFI, TUG, and GS was
      associated with a higher risk of readmission or death within 6 months after
      discharge. The performance of the prediction models was mediocre, and the models
      cannot stand alone as risk stratification tools in clinical practice.

PMID- 29462760
TI  - The scope of parental awareness and mediated training of their children with
      Autism Spectrum Disorders in India.

PMID- 29462761
TI  - A guide to manufacturing CAR T cell therapies.
AB  - In recent years, chimeric antigen receptor (CAR) modified T cells have been used
      as a treatment for haematological malignancies in several phase I and II trials
      and with Kymriah of Novartis and Yescarta of KITE Pharma, the first CAR T cell
      therapy products have been approved. Promising clinical outcomes have yet been
      tempered by the fact that many therapies may be prohibitively expensive to
      manufacture. The process is not yet defined, far from being standardised and
      often requires extensive manual handling steps. For academia, big pharma and
      contract manufacturers it is difficult to obtain an overview over the process
      strategies and their respective advantages and disadvantages. This review details
      current production processes being used for CAR T cells with a particular focus
      on efficacy, reproducibility, manufacturing costs and release testing. By
      undertaking a systematic analysis of the manufacture of CAR T cells from reported
      clinical trial data to date, we have been able to quantify recent trends and
      track the uptake of new process technology. Delivering new processing options
      will be key to the success of the CAR-T cells ensuring that excessive
      manufacturing costs do not disrupt the delivery of exciting new therapies to the
      wide possible patient cohort.

PMID- 29462762
TI  - Acetylcholinesterase of mangrove oyster Crassostrea rhizophorae: A highly
      thermostable enzyme with promising features for estuarine biomonitoring.
AB  - Enzyme biomarkers from several aquatic organisms have been used for assessing the
      exposure to contaminants at sublethal levels. Amongst them, the cholinesterases
      are commonly extracted from several organisms to evaluate/measure organophosphate
      and carbamate neurotoxic effects. Acetylcholinesterase (AChE; EC 3.1.1.7) is an
      enzyme of the group of serine esterases that acts on the hydrolysis of the
      neurotransmitter acetylcholine allowing the intermittence of the nerve impulses
      responsible for the neuronal communication. This enzyme is the main target for
      the action of some pesticides and the inhibition of its activity in bivalve
      mollusks may be used as biomarker due to their filter-feeding habit. In this
      context, the present study aimed to characterize physicochemical and kinetic
      parameters of the AChE extracted from gills and viscera of the oyster Crassostrea
      rhizophorae and investigate the in vitro effect of pesticides (dichlorvos,
      diazinon, chlorpyrifos, methyl-parathion, temephos, carbaryl, carbofuran,
      aldicarb, diflubenzuron and novaluron) in search for assessing its potential as
      biomarker. Specific substrates and inhibitors evidenced the predominance of AChE
      in both tissues. The optimum pH found for gills and viscera AChE were 8.0 and
      8.5, respectively. The maximum peak of activity occurred at 70  degrees C for
      gill AChE and 75  degrees C for viscera AChE. The enzymes of both tissues
      presented remarkable thermostability. The Michaelis-Menten constant for both
      enzymes were 1.32 +/- 0.20 mM for gills and 0.43 +/- 0.12 mM for viscera. The
      Vmax values for gills and viscera were 53.57 +/- 1.72 and 27.71 +/- 1.15 mU/mg,
      respectively. The enzymes were able to reduce the activation energy to 9.75 kcal
      mol-1 (gills) and 11.87 kcal mol-1 (viscera) obtaining rate enhancements of 3.57
      * 105 and 1.01 * 104, respectively, in relation to non-catalyzed reactions. Among
      the pesticides under study, the carbamates carbaryl and carbofuran exerted the
      strongest inhibitory effects on the enzyme activity achieving important degrees
      of inhibition at concentrations below national and international current
      regulations. The first observation of the effects of benzoylurea pesticides
      (diflubenzuron and novaluron) on AChE from mollusks is reported here. The gills
      AChE of C. rhizophorae showed potential to be specific biomarker for the
      carbamate carbaryl while the viscera AChE showed it for carbofuran. According to
      their features, these enzymes may be proposed as promising tools for estuarine
      monitoring as well as biocomponent of biosensor devices.

PMID- 29462763
TI  - Chronic impacts of TiO2 nanoparticles on Populus nigra L. leaf decomposition in
      freshwater ecosystem.
AB  - Titanium dioxide (TiO2) nanoparticles have been applied in diverse commercial
      products, which could lead to toxic effects on aquatic microbes and would inhibit
      some important ecosystem processes. The study aimed to investigate the chronic
      impacts of TiO2 nanoparticles with different concentrations (5, 50, and 500 mg L
      1) on Populus nigra L. leaf decomposition in the freshwater ecosystem. After 50 d
      of decomposing, a significant decrease in decomposition rates was observed with
      higher concentrations of TiO2 nanoparticles. During the period of litter
      decomposition, exposure of TiO2 nanoparticles led to decreases in extracellular
      enzyme activities, which was caused by the reduction of microbial especially
      fungal biomass. In addition, the diversity and composition of the fungal
      community associated with litter decomposition were strongly affected by the
      concentrations of TiO2 nanoparticles. The diversity and composition of the fungal
      community associated with litter decomposition was strongly affected. The
      abundance of Tricladium chaetocladium decreased with the increasing
      concentrations of TiO2 nanoparticles, indicating the little contribution of the
      species to the litter decomposition. In conclusion, this study provided the
      evidence for the chronic exposure effects of TiO2 nanoparticles on the litter
      decomposition and further the functions of freshwater ecosystems.

PMID- 29462764
TI  - Bioinformatic prediction of plant-pathogenicity effector proteins of fungi.
AB  - Effector proteins are important virulence factors of fungal plant pathogens and
      their prediction largely relies on bioinformatic methods. In this review we
      outline the current methods for the prediction of fungal plant pathogenicity
      effector proteins. Some fungal effectors have been characterised and are
      represented by conserved motifs or in sequence repositories, however most fungal
      effectors do not generally exhibit high conservation of amino acid sequence.
      Therefore various predictive methods have been developed around: general
      properties, structure, position in the genomic landscape, and detection of
      mutations including repeat-induced point mutations and positive selection. A
      combinatorial approach incorporating several of these methods is often employed
      and candidates can be prioritised by either ranked scores or hierarchical
      clustering.

PMID- 29462765
TI  - Incidence of haematological malignancies, Eastern Cape Province; South Africa,
      2004-2013.
AB  - BACKGROUND: The incidence of haematological malignancies in Africa's rapidly
      urbanising populations is insufficiently explored. Reliable population-based
      cancer statistics, however, continues to be a scarce resource in Africa and tends
      to be urban biased with limited rural coverage. In addition, many haematological
      malignancies are regarded as rare cancers, a sub-group that often affects the
      young disproportionately and require advanced diagnostic services and facilities
      able to deliver costly sophisticated treatments. This study provides a first
      attempt to estimate the incidence of haematological malignancies among the
      Eastern Cape Province population of South Africa. METHOD: Multiple public- and
      private sector data archives and resources were utilised to optimise the
      identification of incident cases, including clinical records; bone marrow;
      cytology; histology; flow cytometry and cytogenetic records. Crude incidence, age
      and gender-standardised rates are presented and comparison made with existing
      national data and select data from other economically developed countries and
      global institutions. RESULTS: A total of 3603 incident cases were identified
      between 2004 and 2013. Mature lymphoid malignancies accounted for approximately
      60% (n = 2153), myeloma/plasma cell neoplasms 13% (n = 465), acute leukaemia 17%
      (n = 596), chronic myeloid leukaemia 4% (n = 155) and other myeloproliferative
      neoplasms 6% (n = 234) when stratified according to conventional groups. Most
      subtypes increase with age, with male excess. CONCLUSION: Haematological
      malignancies in the Eastern Cape Province show disparities in gender and
      pathology-specific incidence patterns. The present study suggest that
      haematological malignancies are not uncommon in this region and the incidence
      rate of at least one rare subtype, APL, is comparable with some European
      populations.

PMID- 29462766
TI  - Psychosocial stress increases craving for alcohol in social drinkers: Effects of
      risk-taking.
AB  - BACKGROUND: Exposure to stress and trait impulsivity are independent predictors
      of relapse in recovering alcoholics, but potential mechanisms that link these two
      risk-factors in terms of their putative additive or interactive contributions to
      relapse are not known. The aim of this study was to use a model of stress-induced
      relapse to test the hypothesis that acute psychosocial stress increases craving
      for alcohol in social drinkers. We also tested the hypothesis that change in
      craving could be explained by variability in impulsivity and risk-taking.
      METHODS: Participants completed questionnaires to assess drinking behaviour
      (Alcohol Dependence Questionnaire [ADQ]; and an Alcohol Use Disorders
      Identification Test [AUDIT]), craving (Desires for Alcohol Questionnaire [DAQ]
      and impulsivity (Barrett Impulsiveness Scale [BIS]). Participants also completed
      two computer tasks to assess risk-taking and impulsivity, the Balloon Analogue
      Risk Test (BART) and a continuous performance task (CPT). Participants then
      underwent the Trier Social Stress Test (TSST), and completed a final DAQ to
      assess post-stress craving. RESULTS: Participants showed an increase in craving
      following exposure to the TSST. In addition, risk-taking was positively
      correlated with change in craving. CONCLUSIONS: Our data suggests that acute
      psychosocial stress increases subjective craving in social drinkers, but that the
      effects may be trait-dependent, with stress-induced increases in craving
      correlated with risk-taking.

PMID- 29462767
TI  - Psychosocial and neural indicators of resilience among youth with a family
      history of substance use disorder.
AB  - BACKGROUND: Little is known regarding the combined influence of psychosocial and
      neural protective mechanisms against substance use. The present study examined
      the extent to which neuroimaging measures of disinhibition predicted resilience
      against binge drinking and marijuana use among youth with a family history of
      substance use disorder (SUD; FH+), accounting for psychosocial measures of
      behavioral control. METHODS: Participants were 57 FH+ youth from the Michigan
      Longitudinal Study categorized into resilient and high-risk groups based on
      patterns of weekly binge drinking and monthly marijuana use during early
      adulthood. Psychosocial measures of behavioral control (reactive control and
      externalizing behavior during early and late adolescence) and neural measures of
      disinhibition (Go/No-Go task and Monetary Incentive Delay Task (MIDT) measured
      through functional magnetic resonance imaging (fMRI)) were entered sequentially
      in hierarchical logistic regression models to predict resilient versus high-risk
      groups. RESULTS: Greater activation in the right dorsolateral prefrontal cortex
      (DLPFC) during correctly inhibited trials on the Go/No-Go task was a significant
      predictor of resilience (OR = 2.46, p < 0.05), over and above greater reactive
      control in early adolescence (OR = 4.96, p < 0.05) and lower externalizing
      behavior in late adolescence (OR = 0.64, p < 0.05). Neural activation in the
      ventral striatum associated with reward anticipation during the MIDT was not a
      significant predictor of resilience. CONCLUSIONS: Brain function in the right
      DLPFC associated with inhibitory control may be a neural indicator of resilience
      against elevated substance use among FH+ youth, even after accounting for
      psychosocial measures of behavioral control.

PMID- 29462768
TI  - Postpartum contraceptive use and interpregnancy interval among women with opioid
      use disorder.
AB  - OBJECTIVE: The purpose of this study was to describe postpartum contraceptive
      utilization patterns among women with OUD and evaluate the relationship between
      postpartum contraceptive method choice and interpregnancy interval. METHODS: A
      retrospective cohort study was conducted with women in Pennsylvania Medicaid with
      a diagnosis of OUD between 2008 and 2013. Postpartum contraceptive use within 90
      days after delivery was identified through claims data and categorized by
      effectiveness (highly-effective, effective, and no method observed). Kaplan-Meier
      time-to-event analyses and multivariable-adjusted marginal Cox regression models
      were used to evaluate the relationship between postpartum contraceptive method
      choice and interpregnancy interval. Multivariable logistic regression analyses
      were used to identify risk factors predictive of a short interpregnancy interval
      (<=18 months). RESULTS: We identified 7805 women (9260 pregnancies) who had a
      diagnosis of OUD. Nearly three-quarters (74.5%) had no contraceptive method
      observed, 18.1% received an effective method, and only 7.4% received a highly
      effective method (LARC or female sterilization) during the postpartum period. In
      Kaplan-Meier analyses, no significant differences were found in the time-to-next
      pregnancy interval when an effective contraceptive method vs. no contraceptive
      method was used. In multivariable analysis, predictors of a significantly longer
      interpregnancy interval were LARC use (HR 0.43, 95% CI 0.26-0.69), gestational
      hypertension (HR 0.80, 95% CI 0.65-0.97), and age (HR 0.95, 95% CI 0.94-0.96).
      Approximately 20% of women with OUD had a short interpregnancy interval.
      CONCLUSION: Few women with OUD use highly-effective postpartum contraception,
      which is protective against short interpregnancy intervals.

PMID- 29462769
TI  - High status of mercury and selenium in false killer whales (Pseudorca crassidens,
      Owen 1846) stranded on Southern South America: A possible toxicological concern?
AB  - The study was carried out to determine Hg and Se concentrations in false killer
      whales stranded on the Estrecho de Magallanes, Chile, South America. Tissue
      samples of five mature specimens were analyzed (two females and three males).
      Mean Hg concentration in liver 1068 (234) MUg g-1 dry weight (DW) (standard
      deviation in parenthesis) was markedly higher than those in kidney 272 (152) MUg
      g-1 DW, lung 423 (325) MUg g-1 DW, spleen 725 (696) MUg g-1 DW, muscle 118 (94)
      MUg g-1 DW and testicle 18.0 (2.8) MUg g-1 DW. Mean Se concentration in liver,
      398 (75) MUg g-1 DW, was higher than those in kidney 162 (69) MUg g-1 DW, lung
      128 (84) MUg g-1 DW, spleen 268 (245) MUg g-1 DW, muscle 47 (38) MUg g-1 DW and
      testicle 25.4 (2.1) MUg g-1 DW. Positive correlations were found between Hg and
      Se molar concentrations in muscle, lung, spleen and kidney. Molar ratio of Se/Hg
      in liver, lung and muscle were <1, but those in kidney and testicle were markedly
      >1 suggesting a Se protection against Hg toxicity. In all the examined specimens
      Hg values exceeded the toxic thresholds defined for hepatic damage in marine
      mammals, with Se/Hg molar ratios below 1 implying limited protective action of
      Se. Generally, our results showed that individuals are carrying a significant
      burden, reflecting a high exposure to this toxic metal. This constitutes the
      first report on Hg and Se levels for a large subantarctic odontocete in South
      America region, providing insights into their contamination status and with
      information to the understanding of possible impacts on wild populations.

PMID- 29462770
TI  - Mobility of rare earth elements in mine drainage: Influence of iron oxides,
      carbonates, and phosphates.
AB  - The geochemical behavior of rare earth elements (REE) was investigated using
      weathering cells. The influence of sorption and precipitation on dissolved REE
      mobility and fractionation is evaluated using synthetic iron-oxides, carbonates,
      and phosphates. Sorption cell tests are conducted on the main lithologies of the
      expected waste rocks from the Montviel deposit. The sorbed materials are
      characterized using a scanning electron microscope (SEM) equipped with a
      microanalysis system (energy dispersive spectroscopy EDS) (SEM-EDS), X-ray
      diffraction (XRD), and X-ray absorption near edge structure (XANES) in order to
      understand the effect of the synthetic minerals on REE mobility. The results
      confirm that sorption and precipitation control the mobility and fractionation of
      REE. The main sorbent phases are the carbonates, phosphates (present as accessory
      minerals in the Montviel waste rocks), and iron oxides (main secondary minerals
      generated upon weathering of the Montviel lithologies). The XANES results show
      that REE are present as trivalent species after weathering. Thermodynamic
      equilibrium calculations results using Visual Minteq suggest that REE could
      precipitate as secondary phosphates (REEPO4).

PMID- 29462771
TI  - A novel fluorescence "turn-on" sensor based on a photochromic diarylethene for
      the selective detection of Al(III).
AB  - A novel photochromic diarylethene with a triazole-containing 2-(2'-phenoxymethyl)
      benzothiazole group has been synthesized via "click" reaction. The diarylethene
      exhibited good photochromism and photoswitchable fluorescence. Its fluorescence
      emission intensity was enhanced 7-fold by acids, accompanied by the red-shift of
      emission peak from 526nm to 566nm and the concomitant color change from dark to
      bright flavogreen. The diarylethene selectively formed a 1:1 metal complex with
      Al3+, resulting in a "turn-on" fluorescence signal. The complexation - reaction
      between Al3+ and the diarylethene is reversible with the binding constant of
      2.73*103Lmol-1. The limit of detection (LOD) of Al3+ was determined to be 5.94*10
      8molL-1. Based on this unimolecular platform, a logic circuit was fabricated
      using the fluorescence emission intensity at 572nm as the output and the combined
      stimuli of Al3+/EDTA and UV/Vis as the inputs.

PMID- 29462772
TI  - Design and synthesis of novel 1,3-diaryltriazene-substituted sulfonamides as
      potent and selective carbonic anhydrase II inhibitors.
AB  - A series of novel 1,3-diaryltriazene-substituted sulfonamides was synthesized by
      reaction of diazonium salt of 4-amino benzenesulfonamide with substituted
      aromatic amines. The obtained 1,3-diaryltriazene-substituted sulfonamides were
      investigated as inhibitors of four selected human carbonic anhydrase (CA, EC
      4.2.1.1) isoforms (hCA I, hCA II, hCA VII and hCA IX) are involved in various
      diseases such as glaucoma, epilepsy, retinitis pigmentosa, cancer, obesity, etc.
      All these sulfonamides were found to be potent inhibitors of the cytosolic
      isoform hCA II with low nanomolar to sub-nanomolar Kis in the range of 0.2-21.5
      nM, as well as a moderate selectivity against other cytosolic isoforms hCA I and
      hCA VII, and great selectivity against membrane-bound isoform hCA IX was
      observed. Since hCA II is an important drug target for antiglaucoma agents and
      diuretics, these isoform-selective inhibitors may be considered of interest as
      tools for the development of new candidates for these conditions.

PMID- 29462773
TI  - Unmatched speed perceptions between overground and treadmill manual wheelchair
      propulsion in long-term manual wheelchair users.
AB  - BACKGROUND: Manual wheelchair (MWC) propulsion is increasingly assessed on a
      motorized treadmill (TM), which is often considered more ecologically valid than
      stationary rollers. However, no clear consensus on the similarities between
      overground (OG) and TM propulsion has yet been reached. Furthermore, no study has
      investigated the participants' perceptions of propelling a MWC on a TM compared
      to OG. RESEARCH QUESTION: The present study aims to assess the perception of
      speed when propelling on a TM vs OG, and to relate this perception to measured
      spatiotemporal variables, kinetics and work. METHODS: In this repeated-measures
      study, the propulsion's spatiotemporal variables, kinetics, and work of nineteen
      experienced wheelchair users with a spinal cord injury were compared between
      three conditions: 1) OG at a self-selected speed, 2) on a TM at a self-selected
      speed perceived as being similar to the OG speed (TMperceived), and 3) on a TM at
      the same speed as OG (TMmatched). Each variable was compared between conditions
      using an analysis of variance for repeated measures. RESULTS: All participants
      selected a lower speed for TMperceived than OG, with a difference of -0.6 m/s (
      44%). This adaptation may be due to a combination of two factors: 1) the absence
      of speed information, and 2) the feeling of urgency to grab the wheels during the
      recovery phase. The power output, work per cycle, and work per minute were also
      much lower on TMperceived than OG. However, in contrast to other work on MWC
      propulsion on a TM, the kinetic variables assessed were all similar between the
      OG and TMmatched conditions. SIGNIFICANCE: Training on a TM should be performed
      at a speed that matches the OG speed and not at a self-selected speed on the TM,
      which would reduce the power output and work and therefore reduce the efficiency
      of the training.

PMID- 29462774
TI  - Dual-task related gait changes in individuals with trans-tibial lower extremity
      amputation.
AB  - BACKGROUND: The improvement of gait and mobility are major rehabilitation goals
      following lower extremity amputations. However, when living in the community many
      daily activities require the multitasking of motor and cognitive tasks. The dual
      task paradigm can be used to evaluate the concurrent performance of mobility and
      cognitive tasks. RESEARCH QUESTION: The purpose of this study was to evaluate the
      effects of dual-task gait testing in older adults with trans-tibial amputations.
      METHODS: Twenty-four people (15 men, mean age +/- SD, 62.72 +/- 8.59) with trans
      tibial amputation walked on an electronic walkway at i) self-selected comfortable
      pace and ii) self-selected comfortable pace while counting backwards by threes
      from a number randomly selected between 100 and 150. Cognitive performance, in
      the form of corrected response rate, was also evaluated as a single-task.
      RESULTS: The dual-task testing produced poorer performance in velocity (single
      task = 58.15 +/- 23.16 cm/s, dual-task = 50.92 +/- 21.16 cm/s, p = 0.008),
      cadence (single-task = 76.65 +/- 15.84 steps/min, dual-task = 67.85 +/- 15.76
      steps/min, p = 0.002) and stride time (single-task = 1094 +/- 458.28 ms, dual
      task = 1241.44 +/- 513.73 ms, p = 0.005). Step length, stance time and single
      limb support time symmetry were also affected, such that less time was spent on
      the amputated limb during the dual-task testing. SIGNIFICANCE: Dual-task testing
      demonstrated interference resulting in a poor performance in both gait and
      cognitive performance in trans-tibial amputees. Further research is suggested to
      evaluate the change in cognition-mobility effects over time and the relationship
      of this value to future adverse events such as falls and successful outcomes such
      as community ambulation and reintegration.

PMID- 29462775
TI  - Gait analysis in patients with chronic obstructive pulmonary disease: a
      systematic review.
AB  - BACKGROUND: Gait instability is a major fall-risk factor in patients with chronic
      obstructive pulmonary disease (COPD). Clinical gait analysis is a reliable tool
      to predict fall onsets. However, controversy still exists on gait impairments
      associated with COPD. RESEARCH QUESTION: Thus, the aims of this review were to
      evaluate the current understanding of spatiotemporal, kinematic and kinetic gait
      features in patients with COPD. METHODS: In line with PRISMA guidelines, a
      systematic literature search was performed throughout Web of Science, PubMed
      Medline, Scopus, PEDro and Scielo databases. We considered observational cross
      sectional studies evaluating gait features in patients with COPD as their primary
      outcome. Risk of bias and applicability of these papers were assessed according
      to the QUADAS-2 tool. RESULTS: Seven articles, cross-sectional studies published
      from 2011 to 2017, met the inclusion criteria. Sample size of patients with COPD
      ranged 14-196 (mean age range: 64-75 years). The main reported gait abnormalities
      were reduced step length and cadence, and altered variability of spatiotemporal
      parameters. Only subtle biomechanical changes were reported at the ankle level.
      SIGNIFICANCE: A convincing mechanistic link between such gait impairments and
      falls in patients with COPD is still lacking. The paucity of studies, small
      sample sizes, gender and disease status pooling were the main risk of biases
      affecting the results uncertainty. Two research directions emerged: stricter
      cohorts characterization in terms of COPD phenotype and longitudinal studies.
      Quantitative assessment of gait would identify abnormalities and sensorimotor
      postural deficiencies that in turn may lead to better falling prevention
      strategies in COPD.

PMID- 29462776
TI  - Maternal arsenic exposure and birth outcomes: A birth cohort study in Wuhan,
      China.
AB  - Maternal arsenic exposure leads to adverse birth outcomes, but the critical
      window of this susceptibility keeps unclear. To determine whether the
      associations between maternal arsenic exposure and birth outcomes were trimester
      specific, we conducted a birth cohort study of 1390 women from 2014 to 2016 in
      Wuhan, China. We examined associations between total urinary arsenic
      concentrations in three trimesters and birth weight, birth length and the risk of
      small for gestational age (SGA), and the differences of these associations across
      trimesters using generalized estimating equations. Maternal urinary arsenic
      concentrations varied across trimesters and were weakly correlated. Arsenic
      concentrations in the 3rd trimester, but not in the 1st and 2nd trimesters, were
      associated with birth outcomes. For each doubling of arsenic levels in the 3rd
      trimester, birth weight was decreased 24.27 g (95% confidence interval (CI): 
      46.99, -1.55), birth length was decreased 0.13 cm (95% CI: -0.22, -0.04), and the
      risk for SGA birth was increased 25% (95% CI: 1.03, 1.49). Further, stratified
      analyses indicated that these associations were only observed in female infants.
      Our findings indicate maternal arsenic levels in the 3rd trimester seemed to have
      significant impacts on birth outcomes, and also emphasize the public health
      interventions relevance to arsenic exposure in late pregnancy.

PMID- 29462777
TI  - Effects of water warming and acidification on bioconcentration, metabolization
      and depuration of pharmaceuticals and endocrine disrupting compounds in marine
      mussels (Mytilus galloprovincialis).
AB  - Warming and acidification are expected impacts of climate change to the marine
      environment. Besides, organisms that live in coastal areas, such as bivalves, can
      also be exposed to anthropogenic pollutants like pharmaceuticals (PhACs) and
      endocrine disrupting compounds (EDCs). In this study, the effects of warming and
      acidification on the bioconcentration, metabolization and depuration of five
      PhACs (sotalol, sulfamethoxazole, venlafaxine, carbamazepine and citalopram) and
      two EDCs (methylparaben and triclosan) were investigated in the mussel species
      (Mytilus galloprovincialis), under controlled conditions. Mussels were exposed to
      warming and acidification, as well as to the mixture of contaminants up to 15.7
      MUg L-1 during 20 days; followed by 20 days of depuration. All contaminants
      bioconcentrated in mussels with levels ranging from 1.8 MUg kg-1 dry weight (dw)
      for methylparaben to 12889.4 MUg kg-1 dw for citalopram. Warming increased the
      bioconcentration factor (BCF) of sulfamethoxazole and sotalol, whereas
      acidification increased the BCF of sulfamethoxazole, sotalol and methylparaben.
      In contrast, acidification decreased triclosan levels, while both stressors
      decreased venlafaxine and citalopram BCFs. Warming and acidification facilitated
      the elimination of some of the tested compounds (i.e. sotalol from 50% in control
      to 60% and 68% of elimination in acidification and warming respectively).
      However, acidification decreased mussels' capacity to metabolize contaminants
      (i.e. venlafaxine). This work provides a first insight in the understanding of
      aquatic organisms' response to emerging contaminants pollution under warming and
      acidification scenarios.

PMID- 29462778
TI  - Coagulation behavior of humic acid in aqueous solutions containing Cs+, Sr2+ and
      Eu3+: DLS, EEM and MD simulations.
AB  - The coagulation behaviors of humic acid (HA) with Cs+ (10-500 mM), Sr2+ (0.8-10.0
      mM) and Eu3+ (0.01-1.0 mM) at different pH values (2.8, 7.1 and 10.0) were
      acquired through a dynamic light scattering (DLS) technique combined with
      spectroscopic analysis and molecular dynamic (MD) simulations. The coagulation
      rate and the average hydrodynamic diameter (<Dh>) increased significantly as the
      concentration of nuclides increased. <Dh> could be scaled to time t as <Dh>? ta
      at higher Sr2+ concentrations, which shows that HA coagulation is consistent with
      the diffusion-limited colloid aggregation (DLCA) model. Trivalent Eu3+ induced HA
      coagulation at a much lower concentration than bivalent Sr2+ and monovalent Cs+.
      The coagulation value ratio of Sr2+ and Eu3+ to Cs+ is almost proportional to Z
      6, indicating that the HA coagulation process is generally consistent with the
      Schulze-Hardy rule. Spectroscopic analysis indicated that the complexation
      between nuclides and carboxylic/phenolic groups of HA molecules played important
      roles in the coagulation of HA. MD modelling suggested that Sr2+ and Eu3+ ions
      increased the coagulation process through the formation of intra- or inter
      molecular bridges between negatively charged HA molecules, whereas for Cs+, no
      inter-molecular bridges were formed. This work offers new insight into the
      interactions between HA and radionuclides and provides a prediction for the roles
      of HA in the transportation and elimination of radionuclides in severely polluted
      environments.

PMID- 29462779
TI  - Effects of vagus nerve stimulation on heart rate variability in children with
      epilepsy.
AB  - PURPOSE: The aim of this study was to evaluate the effects of vagus nerve
      stimulation (VNS) on heart rate variability (HRV) in children with epilepsy.
      METHODS: The subgroups of HRV, namely time domain (Standard deviation of NN
      interval (SDNN), SDNN index, Standard deviation of the averages of NN intervals
      (SDANN), Root mean square of successive differences (RMMSD), Adjacent NN
      intervals differing by more than 50 ms in the entire recording divided by the
      total number of all NN intervals (PNN50), triangular index) and frequency domain
      (Low-frequency (LF), High-frequency (HF), LF/HF), were investigated in 20
      pediatric patients before and after 6 and 12months of VNS treatment during day
      and night by comparing their data with those of 20 control subjects. In addition,
      subgroups of age, epilepsy duration and localization, and antiepileptic drugs
      (AEDs) were also evaluated if they had further effects on basal HRV levels.
      RESULTS: Increased heart rates (HRs); decreased SDNN, SDANN, RMMSD, and PNN50;
      and increased LF/HF ratios were identified before VNS therapy (p<0.05). Even
      though remarkable improvement was seen after 6months of VNS treatment (p<0.05),
      no further changes were observed in 12-month compared with 6-month levels
      (p>0.05) in all parameters, still even significantly lower than those of controls
      (p<0.05). Longer duration of epilepsy and localization of epileptic focus, such
      as in the temporal lobe, were also found to further contribute to diminished
      basal HRV levels (p<0.05). CONCLUSION: The cardiovascular system is under deep
      sympathetic influence in children with epilepsy. Although VNS seems to provide a
      substantial improvement by achieving increased parasympathetic effects in short
      term therapy, the levels were still lower than those of healthy children after
      either short- or long-term therapy. Therefore, impaired cardiovascular autonomic
      regulation may be associated with the epileptic process itself as well as with
      the contribution of some additional factors. Overall, different aspects such as
      age, epilepsy duration, epileptic focus, seizure frequency, and AEDs should also
      be considered for their further possible effects on HRV during VNS therapy.

PMID- 29462780
TI  - Sensitive analytical method to quantify clindamycin in plasma and microdialysate
      samples: Application in a preclinical pharmacokinetic study.
AB  - Clindamycin is widely used in antimicrobial prophylaxis to prevent surgical site
      infections. Adequate subcutaneous free tissue concentrations should reach
      therapeutic levels, which have to be maintained throughout the surgical procedure
      for antibiotic prophylaxis to be efficient. A method was developed and validated
      using high performance liquid chromatography coupled to a mass spectrometry to
      determine clindamycin concentrations in two biological matrices: plasma, for drug
      monitoring, and subcutaneous microdialysate, to determine free concentrations at
      the incision site. Gradient separation of clindamycin was carried out using a
      reverse phase C18 column eluted with a mixture of mobile phases (1% formic acid
      in water and 1% formic acid in acetonitrile). The monitored transitions were m/z
      425.3 > 377.3 for clindamycin, and m/z 407 > 359 for lincomycin, used as the
      internal standard for plasma samples. Linearity was reached in the 0.5-100 MUg/mL
      range for plasma and 25-1000 ng/mL for microdialysate samples. The method was
      selective, precise, and accurate, and was successfully employed in a preliminary
      pharmacokinetics study to investigate plasma and subcutaneous clindamycin
      penetration, determined by microdialysis, after intravenous administration of a
      50 mg/kg dose to Wistar rats.

PMID- 29462781
TI  - Tripolyphosphate-crosslinked chitosan/poly (ethylene oxide) electrospun
      nanofibrous mats as a floating gastro-retentive delivery system for ranitidine
      hydrochloride.
AB  - The present study describes the fabrication of Tripolyphosphate (TPP)-crosslinked
      nanofibrous mats based on chitosan for use as a floating gastro-retentive
      delivery system. TPP-crosslinked chitosan (CH)/poly (ethylene oxide) (PEO)-
      ranitidine hydrochloride (RH) electrospun nanofibers (75.27 +/- 2.10 nm) were
      prepared by electrospinning 70% v/v acetic acid solutions, and followed by
      crosslinking by TPP anions. The mechanical, structural and morphological
      properties of the prepared nanofibers were evaluated via tensile testing, XRD, FT
      IR, TGA, NMR, AFM and SEM experimental techniques. The prepared nanofibrous mats
      showed a pH sensitive swelling profile with maximum water absorbing at pH 1.2.
      Results obtained from above experimental techniques indicated that crosslinking
      process did not significantly altered morphological property of nanofibers but
      rather decreased their diameter and swelling degree, and increased their
      mechanical properties, thermal stability and bioadhesive strength. Viscosity
      measurements showed that the addition of PEO and RH to the chitosan solution,
      depending to its concentration lead to decrease in the viscosity of its solution.
      Also, floating test showed that the prepared nanofibrous mats remain floated onto
      surface of the dissolution medium for more than 48 h. Based on in- vitro drug
      release data analysis, TPP-crosslinked CH/PEO nanofibrous mats decreased initial
      burst release and it was exhibited a sustained release profile for the RH from
      the TPP-crosslinked CH/PEO-RH electrospun nanofibrous mats.

PMID- 29462782
TI  - Utilizing ELISA-plate based immunopurification and liquid chromatography-tandem
      mass spectrometry for the urinary detection of short- and long acting human
      insulin analogues.
AB  - The measurement of human insulin and its synthetic analogues in biological
      matrices has become increasingly important not only in clinical fields but also
      in doping control. The use of insulin and its analogues have been included in the
      list of prohibited substances published by the World Anti-Doping Agency (WADA).
      This study describes a qualitative method for detection of insulin analogues
      (lispro, aspart, glulisine, glargine, degludec, detemir) in human urine. The
      sample preparation consists of a preconcentration step using ultrafiltration
      followed by an immunoaffinity extraction with an antibody precoated ELISA plate.
      The obtained extracts are analyzed by conventional high-performance liquid
      chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS). The limits
      of detection range between 10 pg/ml and 150 pg/ml. The applicability of the
      method was proven by the analysis of real urine samples obtained from diabetic
      patients treated with synthetic insulin analogues.

PMID- 29462783
TI  - Milling and comilling Praziquantel at cryogenic and room temperatures: Assessment
      of the process-induced effects on drug properties.
AB  - This study is a comprehensive evaluation of praziquantel (PZQ) behavior upon
      grinding considering the influence of milling temperature (cryogenic vs room
      temperature), frequency and time and presence of polymers (milled raw PZQ vs
      comilled PZQ/povidone and PZQ/crospovidone at 50:50 w/w) on two experimental
      responses (residual crystallinity and PZQ recovery). To this aim a full factorial
      design was set up and the responses of the experimental design were statistically
      assessed. The powder temperature, measured in different milling conditions, was
      found to increase with increasing milling frequency and time, up to a maximum
      recorded value of 46.9  degrees C (after 90 min at R.T.), for all the three
      powder systems. When PZQ was ground in RT environment, the recovery was 100%,
      independently from frequency and time of milling. Its residual crystallinity
      remained pronounced (>70%) upon milling, even if treated at the most severe
      conditions. Conversely, when the drug was milled in presence of the polymers, it
      showed a higher tendency to degradation and amorphysation, independently from the
      choice of the polymer. The use of cryogenic conditions, operating at temperatures
      lower than PZQ glass transition, permitted to dramatically reduce PZQ residual
      crystallinity when the drug was ground by itself. In the case of binary mixtures,
      the switch to a cryogenic environment did not affect significantly the
      experimental responses, but permitted to obtain a more predictable trend of both
      drug recovery and residual crystallinity when varying time and frequency of
      milling.

PMID- 29462784
TI  - Transient receptor potential vanilloid 4 (TRPV4) activation by arachidonic acid
      requires protein kinase A-mediated phosphorylation.
AB  - Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable channel of
      the transient receptor potential (TRP) superfamily activated by diverse stimuli,
      including warm temperature, mechanical forces, and lipid mediators such as
      arachidonic acid (AA) and its metabolites. This activation is tightly regulated
      by protein phosphorylation carried out by various serine/threonine or tyrosine
      kinases. It remains poorly understood how phosphorylation differentially
      regulates TRPV4 activation in response to different stimuli. We investigated how
      TRPV4 activation by AA, an important signaling process in the dilation of
      coronary arterioles, is affected by protein kinase A (PKA)-mediated
      phosphorylation at Ser-824. Wildtype and mutant TRPV4 channels were expressed in
      human coronary artery endothelial cells (HCAECs). AA-induced TRPV4 activation was
      blunted in the S824A mutant but was enhanced in the phosphomimetic S824E mutant,
      whereas the channel activation by the synthetic agonist GSK1016790A was not
      affected. The low level of basal phosphorylation at Ser-824 was robustly
      increased by the redox signaling molecule hydrogen peroxide (H2O2). The H2O2
      induced phosphorylation was accompanied by an enhanced channel activation by AA,
      and this enhanced response was largely abolished by PKA inhibition or S824A
      mutation. We further identified a potential structural context dependence of Ser
      824 phosphorylation-mediated TRPV4 regulation involving an interplay between AA
      binding and the possible phosphorylation-induced rearrangements of the C-terminal
      helix bearing Ser-824. These results provide insight into how phosphorylation
      specifically regulates TRPV4 activation. Redox-mediated TRPV4 phosphorylation may
      contribute to pathologies associated with enhanced TRPV4 activity in endothelial
      and other systems.

PMID- 29462785
TI  - The plant sesquiterpene lactone parthenolide inhibits Wnt/beta-catenin signaling
      by blocking synthesis of the transcriptional regulators TCF4/LEF1.
AB  - The Wnt/beta-catenin pathway is essential for embryonic development and
      homeostasis, but excessive activation of this pathway is frequently observed in
      various human diseases, including cancer. Current therapeutic drugs targeting the
      Wnt pathway often lack sufficient efficacy, and new compounds targeting this
      pathway are therefore greatly needed. Here we report that the plant-derived
      natural product parthenolide (PTL), a sesquiterpene lactone, inhibits Wnt
      signaling. We found that PTL dose-dependently inhibits Wnt3a- and CHIR99021
      induced transcriptional activity assessed with the T-cell factor (TCF)/lymphoid
      enhancer factor (LEF) firefly luciferase (TOPFlash) assay in HEK293 cells.
      Further investigations revealed that PTL decreases the levels of the
      transcription factors TCF4/LEF1 without affecting beta-catenin stability or
      subcellular distribution. Moreover, this effect of PTL on TCF4/LEF1 was related
      to protein synthesis rather than to proteasome-mediated degradation. Of note,
      siRNA-mediated knockdown of RPL10, a ribosome protein PTL binds, substantially
      decreased TCF4/LEF1 protein levels and also Wnt3a-induced TOPFlash activities,
      suggesting a potential mechanism by which PTL may repress Wnt/beta-catenin
      signaling. In summary, PTL binds RPL10 and thereby potently inhibits the Wnt/beta
      catenin pathway.

PMID- 29462786
TI  - Distinct properties underlie flavin-based electron bifurcation in a novel
      electron transfer flavoprotein FixAB from Rhodopseudomonas palustris.
AB  - A newly recognized third fundamental mechanism of energy conservation in biology,
      electron bifurcation, uses free energy from exergonic redox reactions to drive
      endergonic redox reactions. Flavin-based electron bifurcation furnishes low
      potential electrons to demanding chemical reactions, such as reduction of
      dinitrogen to ammonia. We employed the heterodimeric flavoenzyme FixAB from the
      diazotrophic bacterium Rhodopseudomonas palustris to elucidate unique properties
      that underpin flavin-based electron bifurcation. FixAB is distinguished from
      canonical electron transfer flavoproteins (ETFs) by a second FAD that replaces
      the AMP of canonical ETF. We exploited near-UV-visible CD spectroscopy to resolve
      signals from the different flavin sites in FixAB and to interrogate the putative
      bifurcating FAD. CD aided in assigning the measured reduction midpoint potentials
      (E degrees  values) to individual flavins, and the E degrees  values tested the
      accepted model regarding the redox properties required for bifurcation. We found
      that the higher-E degrees  flavin displays sequential one-electron (1-e-)
      reductions to anionic semiquinone and then to hydroquinone, consistent with the
      reactivity seen in canonical ETFs. In contrast, the lower-E degrees  flavin
      displayed a single two-electron (2-e-) reduction without detectable accumulation
      of semiquinone, consistent with unstable semiquinone states, as required for
      bifurcation. This is the first demonstration that a FixAB protein possesses the
      thermodynamic prerequisites for bifurcating activity, and the separation of
      distinct optical signatures for the two flavins lays a foundation for mechanistic
      studies to learn how electron flow can be directed in a protein environment. We
      propose that a novel optical signal observed at long wavelength may reflect
      electron delocalization between the two flavins.

PMID- 29462787
TI  - Mechanistic insights into transferable polymyxin resistance among gut bacteria.
AB  - Polymyxins such as colistin are antibiotics used as a final line of defense in
      the management of infections with multidrug-resistant Gram-negative bacteria.
      Although natural resistance to polymyxins is rare, the discovery of a mobilized
      colistin resistance gene (mcr-1) in gut bacteria has raised significant concern.
      As an intramembrane enzyme, MCR-1 catalyzes the transfer of phosphoethanolamine
      (PEA) to the 1 (or 4')-phosphate group of the lipid A moiety of
      lipopolysaccharide, thereby conferring colistin resistance. However, the
      structural and biochemical mechanisms used by this integral membrane enzyme
      remain poorly understood. Here, we report the modeled structure of the full
      length MCR-1 membrane protein. Together with molecular docking, our structural
      and functional dissection of the complex of MCR-1 with its
      phosphatidylethanolamine (PE) substrate suggested the presence of a 12 residue
      containing cavity for substrate entry, which is critical for both enzymatic
      activity and its resultant phenotypic resistance to colistin. More importantly,
      two periplasm-facing helices (PH2 and PH2') of the trans-membrane domain were
      essential for MCR-1 activity. MALDI-TOF MS and thin-layer chromatography assays
      provide both in vivo and in vitro evidence that MCR-1 catalyzes the transfer of
      PEA from the PE donor substrate to its recipient substrate lipid A. Also, the
      chemical modification of lipid A species was detected in clinical species of
      bacteria carrying mcr-1 Our results provide mechanistic insights into
      transferable MCR-1 polymyxin resistance, raising the prospect of rational design
      of small molecules that reverse bacterial polymyxin resistance, as a last-resort
      clinical option to combat pathogens with carbapenem resistance.

PMID- 29462789
TI  - Positioning the 5'-flap junction in the active site controls the rate of flap
      endonuclease-1-catalyzed DNA cleavage.
AB  - Flap endonucleases catalyze cleavage of single-stranded DNA flaps formed during
      replication, repair, and recombination and are therefore essential for genome
      processing and stability. Recent crystal structures of DNA-bound human flap
      endonuclease (hFEN1) offer new insights into how conformational changes in the
      DNA and hFEN1 may facilitate the reaction mechanism. For example, previous
      biochemical studies of DNA conformation performed under non-catalytic conditions
      with Ca2+ have suggested that base unpairing at the 5'-flap:template junction is
      an important step in the reaction, but the new structural data suggest otherwise.
      To clarify the role of DNA changes in the kinetic mechanism, we measured a series
      of transient steps, from substrate binding to product release, during the hFEN1
      catalyzed reaction in the presence of Mg2+ We found that whereas hFEN1 binds and
      bends DNA at a fast, diffusion-limited rate, much slower Mg2+-dependent
      conformational changes in DNA around the active site are subsequently necessary
      and rate-limiting for 5'-flap cleavage. These changes are reported overall by
      fluorescence of 2-aminopurine at the 5'-flap:template junction, indicating that
      local DNA distortion (e.g. disruption of base stacking observed in structures),
      associated with positioning the 5'-flap scissile phosphodiester bond in the hFEN1
      active site, controls catalysis. hFEN1 residues with distinct roles in the
      catalytic mechanism, including those binding metal ions (Asp-34 and Asp-181),
      steering the 5'-flap through the active site and binding the scissile phosphate
      (Lys-93 and Arg-100), and stacking against the base 5' to the scissile phosphate
      (Tyr-40), all contribute to these rate-limiting conformational changes, ensuring
      efficient and specific cleavage of 5'-flaps.

PMID- 29462788
TI  - Unraveling the sequence of cytosolic reactions in the export of GspB adhesin from
      Streptococcus gordonii.
AB  - Many pathogenic bacteria, including Streptococcus gordonii, possess a pathway for
      the cellular export of a single serine-rich-repeat protein that mediates the
      adhesion of bacteria to host cells and the extracellular matrix. This adhesin
      protein is O-glycosylated by several cytosolic glycosyltransferases and requires
      three accessory Sec proteins (Asp1-3) for export, but how the adhesin protein is
      processed for export is not well understood. Here, we report that the S. gordonii
      adhesin GspB is sequentially O-glycosylated by three enzymes (GtfA/B, Nss, and
      Gly) that attach N-acetylglucosamine and glucose to Ser/Thr residues. We also
      found that modified GspB is transferred from the last glycosyltransferase to the
      Asp1/2/3 complex. Crystal structures revealed that both Asp1 and Asp3 are related
      to carbohydrate-binding proteins, suggesting that they interact with
      carbohydrates and bind glycosylated adhesin, a notion that was supported by
      further analyses. We further observed that Asp1 also has an affinity for
      phospholipids, which is attenuated by Asp2. In summary, our findings support a
      model in which the GspB adhesin is sequentially glycosylated by GtfA/B, Nss, and
      Gly and then transferred to the Asp1/2/3 complex in which Asp1 mediates the
      interaction of the Asp1/2/3 complex with the lipid bilayer for targeting of
      matured GspB to the export machinery.

PMID- 29462790
TI  - Fungal lignin peroxidase does not produce the veratryl alcohol cation radical as
      a diffusible ligninolytic oxidant.
AB  - Peroxidases are considered essential agents of lignin degradation by white-rot
      basidiomycetes. However, low-molecular-weight oxidants likely have a primary role
      in lignin breakdown because many of these fungi delignify wood before its
      porosity has sufficiently increased for enzymes to infiltrate. It has been
      proposed that lignin peroxidases (LPs, EC 1.11.1.14) fulfill this role by
      oxidizing the secreted fungal metabolite veratryl alcohol (VA) to its aryl cation
      radical (VA+*), releasing it to act as a one-electron lignin oxidant within woody
      plant cell walls. Here, we attached the fluorescent oxidant sensor BODIPY 581/591
      throughout beads with a nominal porosity of 6 kDa and assessed whether peroxidase
      generated aryl cation radical systems could oxidize the beads. As positive
      control, we used the 1,2,4,5-tetramethoxybenzene (TMB) cation radical, generated
      from TMB by horseradish peroxidase. This control oxidized the beads to depths
      that increased with the amount of oxidant supplied, ultimately resulting in
      completely oxidized beads. A reaction-diffusion computer model yielded oxidation
      profiles that were within the 95% confidence intervals for the data. By contrast,
      bead oxidation caused by VA and the LPA isozyme of Phanerochaete chrysosporium
      was confined to a shallow shell of LP-accessible volume at the bead surface,
      regardless of how much oxidant was supplied. This finding contrasted with the
      modeling results, which showed that if the LP/VA system were to release VA+*, it
      would oxidize the bead interiors. We conclude that LPA releases insignificant
      quantities of VA+* and that a different mechanism produces small ligninolytic
      oxidants during white rot.

PMID- 29462791
TI  - The cellular chloride channels CLIC1 and CLIC4 contribute to virus-mediated cell
      motility.
AB  - Ion channels regulate many aspects of cell physiology, including cell
      proliferation, motility, and migration, and aberrant expression and activity of
      ion channels is associated with various stages of tumor development, with K+ and
      Cl- channels now being considered the most active during tumorigenesis.
      Accordingly, emerging in vitro and preclinical studies have revealed that
      pharmacological manipulation of ion channel activity offers protection against
      several cancers. Merkel cell polyomavirus (MCPyV) is a major cause of Merkel cell
      carcinoma (MCC), primarily because of the expression of two early regulatory
      proteins termed small and large tumor antigens (ST and LT, respectively). Several
      molecular mechanisms have been attributed to MCPyV-mediated cancer formation but,
      thus far, no studies have investigated any potential link to cellular ion
      channels. Here we demonstrate that Cl- channel modulation can reduce MCPyV ST
      induced cell motility and invasiveness. Proteomic analysis revealed that MCPyV ST
      up-regulates two Cl- channels, CLIC1 and CLIC4, which when silenced, inhibit
      MCPyV ST-induced motility and invasiveness, implicating their function as
      critical to MCPyV-induced metastatic processes. Consistent with these data, we
      confirmed that CLIC1 and CLIC4 are up-regulated in primary MCPyV-positive MCC
      patient samples. We therefore, for the first time, implicate cellular ion
      channels as a key host cell factor contributing to virus-mediated cellular
      transformation. Given the intense interest in ion channel modulating drugs for
      human disease. This highlights CLIC1 and CLIC4 activity as potential targets for
      MCPyV-induced MCC.

PMID- 29462792
TI  - Arabidopsis thaliana GH3.15 acyl acid amido synthetase has a highly specific
      substrate preference for the auxin precursor indole-3-butyric acid.
AB  - Various phytohormones control plant growth and development and mediate biotic and
      abiotic stress responses. Gretchen Hagen 3 (GH3) acyl acid amido synthetases are
      plant enzymes that typically conjugate amino acids to indole-3-acetic acid (IAA)
      or jasmonic acid (JA) to inactivate or activate these phytohormones,
      respectively; however, the physiological and biological roles of many of these
      enzymes remain unclear. Using a biochemical approach, we found that the
      Arabidopsis thaliana GH3.15 (AtGH3.15) preferentially uses indole-3-butyric acid
      (IBA) and glutamine as substrates. The X-ray crystal structure of the
      AtGH3.15.AMP complex, modeling of IBA in the active site, and biochemical
      analysis of site-directed mutants provide insight on active site features that
      lead to AtGH3.15's preference for IBA. Assay-based in planta analysis of AtGH3.15
      overexpressing lines indicated that their root elongation and lateral root
      density were resistant to IBA treatment but not to treatment with either IAA or
      JA. These findings suggest that AtGH3.15 may play a role in auxin homeostasis by
      modulating the levels of IBA for peroxisomal conversion to IAA. Analysis of
      AtGH3.15 promoter-driven yellow fluorescent protein reporter lines revealed that
      AtGH3.15 is expressed at significant levels in seedlings, roots, and parts of the
      siliques. We conclude that AtGH3.15 is unique in the GH3 protein family for its
      role in modifying IBA in auxin homeostasis and that it is the first GH3 protein
      shown to primarily modify a plant growth regulator other than IAA and JA.

PMID- 29462794
TI  - Filling the mitochondrial copper pool.
AB  - A host of critical metalloproteins reside in mitochondria, where metallation
      occurs within the organelle after protein import. Although the pathways by which
      proteins are imported into the mitochondria are well known, the mechanisms by
      which their metal partners are imported are more obscure. A new study by Boulet
      et al. demonstrates that the mammalian SLC25A3 inner membrane transporter,
      previously known as a phosphate carrier, is also a functional Cu(I) importer,
      clarifying the source of mitochondrial copper and raising new questions about
      cellular copper homeostasis.

PMID- 29462793
TI  - The human platelet antigen-1b (Pro33) variant of alphaIIbbeta3 allosterically
      shifts the dynamic conformational equilibrium of this integrin toward the active
      state.
AB  - Integrins are heterodimeric cell-adhesion receptors comprising alpha and beta
      subunits that transmit signals allosterically in both directions across the
      membrane by binding to intra- and extracellular components. The human platelet
      antigen-1 (HPA-1) polymorphism in alphaIIbbeta3 arises from a Leu -> Pro exchange
      at residue 33 in the genu of the beta3 subunit, resulting in Leu33 (HPA-1a) or
      Pro33 (HPA-1b) isoforms. Although clinical investigations have provided
      conflicting results, some studies have suggested that Pro33 platelets exhibit
      increased thrombogenicity. Under flow-dynamic conditions, the Pro33 variant
      displays prothrombotic properties, characterized by increased platelet adhesion,
      aggregate/thrombus formation, and outside-in signaling. However, the molecular
      events underlying this prothrombotic phenotype have remained elusive. As residue
      33 is located >80 A away from extracellular binding sites or transmembrane
      domains, we hypothesized that the Leu -> Pro exchange allosterically shifts the
      dynamic conformational equilibrium of alphaIIbbeta3 toward an active state.
      Multiple microsecond-long, all-atom molecular dynamics simulations of the
      ectodomain of the Leu33 and Pro33 isoforms provided evidence that the Leu -> Pro
      exchange weakens interdomain interactions at the genu and alters the structural
      dynamics of the integrin to a more unbent and splayed state. Using FRET analysis
      of fluorescent proteins fused with alphaIIbbeta3 in transfected HEK293 cells, we
      found that the Pro33 variant in its resting state displays a lower energy
      transfer than the Leu33 isoform. This finding indicated a larger spatial
      separation of the cytoplasmic tails in the Pro33 variant. Together, our results
      indicate that the Leu -> Pro exchange allosterically shifts the dynamic
      conformational equilibrium of alphaIIbbeta3 to a structural state closer to the
      active one, promoting the fully active state and fostering the prothrombotic
      phenotype of Pro33 platelets.

PMID- 29462795
TI  - Positive zip coding in small protein translocation.
AB  - Most newly synthesized proteins destined for the secretory pathway contain a
      signal peptide (SP) that triggers cotranslational translocation into the
      endoplasmic reticulum (ER). However, how small polypeptides undergo ER
      translocation is not fully understood. In this issue of JBC, Guo et al. describe
      a mechanism for posttranslational translocation of small secretory proteins
      featuring a positive charge within the SP N-terminal region. Defects in this
      element disrupt proper secretion and explain the effects of genetic mutations
      associated with one type of diabetes.

PMID- 29462796
TI  - P38/TRHr-Dependent Regulation of TPO in Thyroid Cells Contributes to the
      Hypothyroidism of Triclosan-Treated Rats.
AB  - BACKGROUND/AIMS: Triclosan, as an antimicrobial agent and a potential endocrine
      disruptor, has been used extensively in diverse products, resulting in widespread
      human exposure. In recent years, studies suggest that triclosan could disturb
      thyroid functions and decline thyroid hormones (THs). METHODS: To verify our
      hypothesis that the MAPK pathway may function significantly in triclosan-induced
      hypothyroidism, Sprague-Dawley rats were gavaged with triclosan for 31
      consecutive days; Nthy-ori 3-1 cells were treated with triclosan in the
      presence/absence of NAC, inhibitors (SB203580 and SB202474), or TRHr siRNA.
      Tissues and/or cells were analyzed by several techniques including transmission
      electron microscopy, confocal laser scanning microscopy, gene silencing, western
      blot, and real-time PCR. RESULTS: Triclosan led to histopathologic changes in the
      thyroid and decreases in triiodothyronine (T3) and thyroxine (T4). Triclosan
      stimulated ROS production and oxidative stress occurrence, thereby activating the
      p38 pathway in vivo and in vitro. Thyrotropin releasing hormone receptor (TRHr)
      was induced when the p38 pathway was activated, and was suppressed when that
      pathway was inhibited. Moreover, thyroid peroxidase (TPO) was restrained and
      modulated by the p38/TRHr pathway after triclosan treatment. Furthermore,
      deiodinase 3 (D3) and hepatic enzymes (Ugt2b1, CYP1a1, CYP1a2, CYP2b1, CYP3a1,
      and Sult1e1) were also induced by triclosan. CONCLUSION: Taken together, p38/TRHr
      dependent regulation of TPO in thyroid cells contributes to the hypothyroidism of
      triclosan-treated rats.

PMID- 29462797
TI  - Functional SNP in the 3'UTR of PON1 is Associated with the Risk of Calcific
      Aortic Valve Stenosis via MiR-616.
AB  - BACKGROUND/AIMS: Previous studies have examined the associations between the
      single nucleotide polymorphism in the Paraoxonase 1 (PON1) gene and development
      of calcific aortic valve stenosis (CAVS). The association between functional SNP
      in 3'UTR of PON1 and the risk of CAVS, however, is unclear. In this study, we
      investigated the role of SNP in the regulation of PON1 expression via miR-616, as
      well as the association of SNP with the risk of CAVS. METHODS: Two hundred and
      sixteen patients with CAVS and 243 CAVS-free participants were recruited in this
      study.They all obtained transthoracic echocardiogram and the ejection fraction
      (EF) and aortic valve area were recorded and analyzed. The PON1 expression were
      measured by western blot, Quantitative Real-Time Polymerase Chain Reaction were
      used to examine the transcriptional activity of miR-616 and PON1. Differences
      between CVAS patients and controls in terms of genotype frequency distribution
      and the estimates of Hardy-Weinberg equilibrium were evaluated using chi-square
      tests. Logistic regression modeling was used to determine the association between
      the independent effect of rs3735590 SNP and the interaction between genotype,
      PON1 activity, and other covariates on lipids and CAVS risk. All statistical
      analyses were performed using SPSS, version 17.0.1 for Windows (SPSS Inc.,
      Chicago, IL). A p value of < 0 .05 was considered significant for all analyses.
      RESULTS: This study confirmed that PON1 is a validated target gene of miR-616 in
      liver cells. The relative quantification representing the expression of PON1 mRNA
      and the serum level of PON1 protein was decreased in the TT genotype. Moreover,
      the expression of PON1 had a negative regulatory relationship with the expression
      of miR-616(r=-0.3959, P<0.05) in human tissues. The patients with CT OR TT
      genotype at loci rs3735590 had a lower risk of CAVS than patients with the CC
      genotype. CONCLUSIONS: Our results suggest that functional SNP in the 3'UTR of
      PON1 regulates the expression of PON1 via miR-616, and such SNP is associated
      with the risk of CAVS in human.

PMID- 29462798
TI  - Serum FGF21 Is Associated with Future Cardiovascular Events in Patients with
      Coronary Artery Disease.
AB  - OBJECTIVES: To investigate whether serum fibroblast growth factor 21 (FGF21)
      levels can be used to predict the future development of major adverse
      cardiovascular events (MACEs). METHODS: This study included 253 patients who
      received subsequent follow-up, and complete data were collected for 234 patients.
      Independent predictors of MACEs were identified by using the Cox proportional
      hazards regression analysis. The prognostic value of FGF21 levels for MACEs was
      evaluated by Kaplan-Meier survival analysis. RESULTS: Of 229 patients finally
      enrolled in the analysis, 27/60 without coronary artery disease (CAD) at baseline
      experienced a MACE, and 132/169 patients with CAD at baseline experienced a MACE.
      Among patients with CAD at baseline, serum FGF21 levels were significantly higher
      in patients with MACEs (p < 0.05) than in patients without MACEs. Kaplan-Meier
      survival analysis showed patients with a higher serum FGF21 had a significantly
      lower event-free survival (p = 0.001) than those with a lower level. Further Cox
      proportional-hazards regression analysis, including the traditional risk factors
      for cardiovascular disease, showed that serum FGF21 was an independent predictor
      of MACE occurrence. CONCLUSIONS: In patients with CAD at baseline, an elevated
      serum FGF21 level was associated with the development of a MACE in the future.

PMID- 29462799
TI  - MicroRNA-27a Suppresses Detrusor Fibrosis in Streptozotocin-Induced Diabetic Rats
      by Targeting PRKAA2 Through the TGF-beta1/Smad3 Signaling Pathway.
AB  - BACKGROUND/AIMS: We examined the effects of microRNA-27a (miR-27a) on detrusor
      fibrosis in streptozotocin (STZ)-induced diabetic rats. METHODS: Eighty healthy
      Sprague-Dawley (SD) rats were randomly allocated into control, diabetic, miR-27a
      mimics, mimics control, miR-27a inhibitors, inhibitors control, siRNA-PRKAA2
      (siPRKAA2) and inhibitors + siPRKAA2 groups (the latter 7 groups were established
      as STZ-induced diabetic rat models and treated in different manners). Detrusor
      cell apoptosis in bladder tissues was determined through terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL)
      staining. Detrusor cells were assigned to the blank, miR-27a mimics, mimics
      control, miR-27a inhibitors, inhibitors control, siPRKAA2 and inhibitors +
      siPRKAA2 groups. Flow cytometry determined the cell cycle stage and apoptosis.
      Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and
      western blotting (WB) were used to assess the expression of miR-27a, PRKAA2, TGF
      beta1, Smad3, p-Smad3, fibronectin (FN), connective tissue growth (CTGF), and
      collagen-I (COL-I) in tissues and cells. RESULTS: Compared with the control
      group, the diabetic, miR-27a mimics, and siPRKAA2 groups showed reduced weight
      and PRKAA2 expression, but elevated blood glucose, serum creatinine (sCr), blood
      urea nitrogen (BUN), cell apoptosis, and expression of TGF-beta1, Smad3, FN, COL
      I, CTGF, and p-Smad3. The opposite trend was observed in the miR-27a inhibitors
      group. PRKAA2 is a target gene of miR-27a. Compared to the blank group, the miR
      27a mimics and siPRKAA2 groups indicated markedly increased TGF-beta1, Smad3, FN,
      COL-I, CTGF and p-Smad3 expression; decreased PRKAA2 expression; and increased
      cell apoptosis. The miR-27a inhibitors group showed the opposite trend.
      CONCLUSION: These results indicate that miR-27a may contribute to detrusor
      fibrosis in STZ-induced diabetic rats by targeting PRKAA2 via the TGF-beta1/Smad3
      signaling pathway.

PMID- 29462801
TI  - Complementary Medicine Research: Auch ein Geschichtsbuch der SMGP.

PMID- 29462802
TI  - Treatment of Chronic Immune Thrombocytopenic Purpura with Homeopathic Dilutions
      of Patient Blood.
AB  - BACKGROUND: Conventional or homeopathic treatment of chronic immune
      thrombocytopenic purpura (ITP) is often difficult. The use of homeopathic
      dilutions of patient blood (HPB) for immunomodulation has been described, which
      inspired us to try the method in an ITP case. CASE REPORT: A 2-year-old girl with
      chronic ITP was treated with homeopathic dilutions of her own capillary blood,
      given orally over 5 months. Immediately after treatment onset there was a rapid
      normalization of the thrombocyte counts. Within 6 weeks, they rose from 15,000/ul
      to 254,000/ul. After treatment stop, they decreased to 155,000/ul, increased
      again spontaneously to 270,000/ul and remained within normal range for over 3
      years. CONCLUSIONS: Oral administration of homeopathic dilutions of capillary
      patient blood may possibly be an effective treatment in chronic ITP. If our
      results can be reproduced, this will revolutionize the treatment of ITP.

PMID- 29462800
TI  - Anti- Versus Pro-Inflammatory Metabololipidome Upon Cupping Treatment.
AB  - BACKGROUND/AIMS: This study aimed to explore the metabololipidome in mice upon
      cupping treatment. METHODS: A nude mouse model mimicking the cupping treatment in
      humans was established by administrating four cupping sets on the back skin for
      15 minutes. UPLC-MS/ MS was performed to determine the PUFA metabolome in mice
      skin and blood before and after cupping treatment. The significantly changed
      lipids were administered in macrophages to assess the production of pro
      inflammatory cytokines IL-6 and TNF-alpha by ELISA. RESULTS: The anti
      inflammatory lipids, e.g. PGE1, 5,6-EET, 14,15-EET, 10S,17S-DiHDoHE, 17R-RvD1,
      RvD5 and 14S-HDoHE were significantly increased while pro-inflammatory lipids,
      e.g. 12-HETE and TXB2 were deceased in the skin or plasma post cupping treatment.
      Cupping treatment reversed the LPS-stimulated IL-6 and TNF-alpha expression in
      mouse peritoneal exudates. Moreover, 5,6-EET, PGE1 decreased the level of TNF
      alpha, while 5,6-EET, 5,6-DHET downregulated IL-6 production in macrophages.
      Importantly, 14,15-EET and 14S-HDoHE inhibited both IL-6 and TNF-alpha induced by
      lipopolysaccharide (LPS). 17-RvD1, RvD5 and PGE1 significantly reduced the LPS
      initiated TNF-alpha, while TXB2 and 12-HETE further upregulated the LPS-enhanced
      IL-6 and TNF-alpha expression in macrophages. CONCLUSION: Our results reveal the
      identities of anti-inflammatory versus pro-inflammatory metabolipidome and
      suggest the potential therapeutic mechanism of cupping treatment.

PMID- 29462803
TI  - Chromosome Painting in Tyrant Flycatchers Confirms a Set of Inversions Shared by
      Oscines and Suboscines (Aves, Passeriformes).
AB  - Tyrannidae is the largest family of Passeriformes in the Neotropical region.
      However, despite an interesting chromosomal diversity, there are only few
      cytogenetic studies of this family, and most of these are based on conventional
      cytogenetics. Hence, we analyzed here the chromosomal diversity and karyotypical
      evolution of this group by chromosome painting in 3 different species - Pitangus
      sulphuratus, Serpophaga subcristata, and Satrapa icterophrys - and make
      comparisons with previous data. In addition to chromosome painting with Gallus
      gallus (GGA) and Leucopternis albicollis (LAL) probes, karyotypes were analyzed
      by conventional staining, C-banding, and FISH with 18S rDNA and telomeric probes.
      Although this family is characterized by extensive chromosomal variation, we
      found similar karyotypes and diploid numbers ranging from 2n = 80 in P.
      sulphuratus to 2n = 82 in S. subcristata and S. icterophrys. Constitutive
      heterochromatin was located centromerically in all 3 species. Clusters of 18S
      rDNA were present in 1 pair of microchromosomes, except in S. subcristata, where
      2 pairs of microchromosomes were labeled. No interstitial telomeric sequences
      were detected. GGA and LAL whole-chromosome probes revealed the occurrence of
      fissions and both paracentric and pericentric inversions commonly seen in other
      Passeriformes. In general terms, tyrants show the typical karyotype found in
      Passeriformes, suggesting that the observed rearrangements occurred before the
      division of the suborders Oscines and Suboscines.

PMID- 29462804
TI  - Angiotensin II Regulates Th1 T Cell Differentiation Through Angiotensin II Type 1
      Receptor-PKA-Mediated Activation of Proteasome.
AB  - BACKGROUND/AIMS: Naive CD4+ T cells differentiate into T helper cells (Th1 and
      Th2) that play an essential role in the cardiovascular diseases. However, the
      molecular mechanism by which angiotensin II (Ang II) promotes Th1 differentiation
      remains unclear. The aim of this study was to determine whether the Ang II
      induced Th1 differentiation regulated by ubiquitin-proteasome system (UPS).
      METHODS: Jurkat cells were treated with Ang II (100 nM) in the presence or
      absence of different inhibitors. The gene mRNA levels were detected by real-time
      quantitative PCR analysis. The protein levels were measured by ELISA assay or
      Western blot analysis, respectively. RESULTS: Ang II treatment significantly
      induced a shift from Th0 to Th1 cell differentiation, which was markedly blocked
      by angiotensin II type 1 receptor (AT1R) inhibitor Losartan (LST). Moreover, Ang
      II significantly increased the activities and the expression of proteasome
      catalytic subunits (beta1, beta1i, beta2i and beta5i) in a dose- and time
      dependent manner. However, Ang II-induced proteasome activities were remarkably
      abrogated by LST and PKA inhibitor H-89. Mechanistically, Ang II-induced Th1
      differentiation was at least in part through proteasome-mediated degradation of
      IkappaBalpha and MKP-1 and activation of STAT1 and NF-kappaB. CONCLUSIONS: This
      study for the first time demonstrates that Ang II activates AT1R-PKA-proteasome
      pathway, which promotes degradation of IkappaBalpha and MKP-1 and activation of
      STAT1 and NF-kappaB thereby leading to Th1 differentiation. Thus, inhibition of
      proteasome activation might be a potential therapeutic target for Th1-mediated
      diseases.

PMID- 29462805
TI  - Low-Intensity Pulsed Ultrasound Prevents the Oxidative Stress Induced Endothelial
      Mesenchymal Transition in Human Aortic Endothelial Cells.
AB  - BACKGROUND/AIMS: Endothelial-mesenchymal transition (EndMT) has been shown to
      take part in the generation and progression of diverse diseases, involving a
      series of changes leading to a loss of their endothelial characteristics and an
      acquirement of properties typical of mesenchymal cells. Low-intensity pulsed
      ultrasound (LIPUS) is a new therapeutic option that has been successfully used in
      fracture healing. However, whether LIPUS can inhibit oxidative stress-induced
      endothelial cell damages through inhibiting EndMT remained unknown. This study
      aimed to investigate the protective effects of LIPUS against oxidative stress
      induced endothelial cell damages and the underlying mechanisms. METHODS: EndMT
      was induced by H2O2 (100 um for seven days). Human aortic endothelial cells
      (HAECs) were exposed to H2O2 with or without LIPUS treatment for seven days. The
      expression of EndMT markers (CD31, VE-cadherin, FSP1 and alpha-SMA) were
      analyzed. The levels of total and phosphorylated PI3K and AKT proteins were
      detected by Western Blot analysis. Cell chemotaxis was determined by wound
      healing and transwell assay. RESULTS: LIPUS relieved EndMT by decreasing ROS
      accumulation and increasing activation of the PI3K signaling cascade. LIPUS
      alleviated the migration of EndMT-derived mesenchymal-like cells through reducing
      extracellular matrix (ECM) deposition that is associated with matrix
      metallopeptidase (MMP) proteolytic activity and collagen production. CONCLUSION:
      LIPUS produces cytoprotective effects against oxidative injuries to endothelial
      cells through suppressing the oxidative stress-induced EndMT, activating the
      PI3K/AKT pathway under oxidative stress, and limiting cell migration and
      excessive ECM deposition.

PMID- 29462806
TI  - HGF and BFGF Secretion by Human Adipose-Derived Stem Cells Improves Ovarian
      Function During Natural Aging via Activation of the SIRT1/FOXO1 Signaling
      Pathway.
AB  - BACKGROUND/AIMS: Human adipose-derived stem cells (hADSCs) are a potential
      therapeutic option for clinical applications because of their ability to produce
      cytokines and their capacity for trilineage differentiation. To date, few
      researchers have investigated the effects of hADSCs on natural ovarian aging
      (NOA). METHODS: An NOA mouse model and human ovarian granule cells (hGCs)
      collected from individuals with NOA were prepared to assess the therapeutic
      effects and illuminate the mechanism of hADSCs in curing NOA. Enzyme-linked
      immunosorbent assay was used to detect the serum levels of sex hormones and
      antioxidative enzymes. The proliferation rate and marker expression level of hGCs
      were measured by flow cytometry (FACS). Cytokines were measured by a protein
      antibody array methodology. Western blot assays were used to determine the
      protein expression levels of SIRT1 and FOXO1. RESULTS: Our results showed that
      hADSCs displayed therapeutic activity against ovarian function in an NOA mouse
      model, increasing the proliferation rate and marker expression level of hGCs.
      Furthermore, the yields of hADSC-secreted HGF and bFGF were higher than those of
      other growth factors. FACS showed that combination treatment with the growth
      factors HGF and bFGF more strongly promoted proliferation and inhibited apoptosis
      in hGCs than HGF or bFGF treatment alone. FACS and ELISA revealed that the
      combination treatment with both growth factors inhibited oxidative stress more
      forcefully than treatments with only one of these growth factors. In addition,
      protein assays demonstrated that combination treatment with both growth factors
      suppressed oxidative stress by up-regulating the expression of SIRT1 and FOXO1.
      CONCLUSION: These findings demonstrate for the first time the molecular cascade
      and related cell biology events involved in the mechanism by which HGF and bFGF
      derived from hADSCs improved ovarian function during natural aging via reduction
      of oxidative stress by activating the SIRT1/FOXO1 signaling pathway.

PMID- 29462807
TI  - The Return of Fear: Variation of the Serotonin Transporter Gene Predicts Outcome
      of a Highly Standardized Exposure-Based One-Session Fear Treatment.
AB  - BACKGROUND: Methodological problems of existing research, such as the application
      of unstandardized treatments in heterogeneous samples, has hampered clear
      conclusions about the extent and direction to which allelic variation of the
      serotonin transporter gene-linked polymorphic region (5- HTTLPR) is associated
      with a differential response to psychological treatment. The present study aimed
      to investigate the effects of the 5-HTTLPR genotype on treatment outcome under
      highly standardized environmental conditions. METHODS: We treated 222 medication
      free adults highly fearful of spiders, dental surgeries or blood, injuries and
      injections with a highly standardized exposure-based 1-session treatment and
      genotyped them for the 5-HTTLPR. Participants' subjective fear was assessed
      before, immediately after treatment and at 7 months of follow-up. RESULTS: There
      were no differences between 5-HTTLPR genotypes in treatment outcome effects at
      the immediate posttreatment assessment. However, we observed a highly significant
      genotype * treatment effect (p = 0.004) at the 7-month follow-up. Fear levels of
      homozygous S allele carriers differed from those heterozygous (p = 0.026) and
      homozygous (p = 0.012) for the L allele. Compared to posttreatment assessment, LL
      allele carriers exhibited a further fear decrease at the follow-up assessment. In
      contrast, SS allele carriers displayed a strong return of fear. CONCLUSIONS:
      Results suggest that genetic variation of the serotonin transporter is associated
      with differential stability of inhibitory learning processes, potentially
      reflecting heightened susceptibility for context-related processes that
      facilitate a return of fear in S allele carriers. If replicated, results suggest
      the 5-HTTLPR might represent a biomarker for the long-term outcome of brief
      exposure-based fear treatments and might inform genotype-based selection of
      psychotherapeutic interventions.

PMID- 29462808
TI  - Bronchial Carcinoid? Interventional Pulmonologist First!

PMID- 29462809
TI  - Liver Plays a Major Role in FGF-21 Mediated Glucose Homeostasis.
AB  - BACKGROUND/AIMS: The liver is a vital organ in vertebrates and has a wide range
      of functions, including glucose absorption, glycogen storage and glucose
      production. Fibroblast growth factor (FGF)-21 is a metabolic regulator that is
      primarily produced by the liver. In this paper, we studied the effect of FGF-21
      on glucose metabolism in the liver. METHODS: The glucose uptake of cells was
      detected by 2-Deoxy-d-[3H] glucose; the synergy between insulin and FGF-21 was
      evaluated. The mRNA expression of GLUT1-4, G6Pase and PEPCK was detected by real
      time PCR. Glycogen synthesis was examined by the anthrone method. Blood samples
      to monitor glucose in db/db diabetic mice were obtained by tail snip. Glucose
      metabolism in the liver and adipose tissues was observed by fluorescence
      microscopy. RESULTS: In this study, FGF-21 stimulated glucose uptake by liver
      cells in both a dose and time-dependent manner, and at the same time, FGF-21
      specifically stimulated GLUT1 expression in the liver cells. Furthermore, FGF-21
      demonstrated a synergistic effect with insulin on glucose absorption, which is in
      accordance with enhanced GLUT-1 and -4 expression. Treatment with FGF-21
      increased glycogen storage in liver cells. Consistent with in vitro results, FGF
      21 lowered the plasma glucose level and stimulated GLUT1 expression and glycogen
      synthesis in db/db diabetic mice. Simultaneously, FGF-21 inhibited the gene
      expression of G6Pase and PEPCK. CONCLUSION: Our results suggest that FGF-21
      clears up plasma glucose by stimulating glucose absorption in the liver of
      diabetic animals and decreases glucose release from the liver by inhibiting
      gluconeogenesis. Overall, these data indicate that the liver is an important
      target organ of FGF-21 to regulate glucose metabolism.

PMID- 29462810
TI  - Consumption of Amaranth Induces the Accumulation of the Antioxidant Protein
      Paraoxonase/Arylesterase 1 and Modulates Dipeptidyl Peptidase IV Activity in
      Plasma of Streptozotocin-Induced Hyperglycemic Rats.
AB  - BACKGROUND/AIM: Amaranth is a source of several bioactive compounds, among which
      peptides with inhibitory activity upon dipeptidyl peptidase IV (DPP-IV) have been
      reported. However, there is no information about the action of amaranth DPP-IV
      inhibitory peptides using in vivo models. The aim of this work was to evaluate
      the effect of amaranth consumption on plasma and kidney DPP-IV activity as well
      the changes in plasma proteome profile of streptozotocin (STZ)-induced
      hyperglycemic rats. METHODS: Rats were fed for 12 weeks with a diet containing
      20% popped amaranth grain. Kidneys and blood samples were collected for lipid
      profile, DPP-IV activity and expression, and proteomic analysis. RESULTS: Total
      cholesterol and DPP-IV activity in plasma was increased in hyperglycemic rats,
      but this effect was reverted by amaranth consumption. Triacylglycerols were
      increased in the hyperglycemic group fed amaranth, and the highest levels of high
      density lipoproteins were also observed in this group. These data correlated with
      the accumulation of apolipoprotein A-II in plasma. Accumulation of the
      antioxidant protein paraoxonase/arylesterase 1 in STZ-induced hyperglycemic rats
      was observed when amaranth was supplied in the diet. CONCLUSION: This study
      provides new insights into the molecular mechanisms by which amaranth exerts its
      beneficial health action in a hyperglycemic state.

PMID- 29462811
TI  - Infraorbital Nerve Located Medially to Postoperative Maxillary Cysts: A Risk of
      Endonasal Surgery.
AB  - BACKGROUND/AIMS: This study aimed to examine variations in the location of the
      infraorbital nerve relative to postoperative maxillary cysts to assess the
      potential risk of nerve injury during endonasal marsupialization. METHODS:
      Coronal computed tomography images of 130 patients (162 sides) with postoperative
      maxillary cysts who visited our clinic between 2003 and 2014 were reviewed from
      the viewpoint of the anatomical relationship between the infraorbital nerves and
      cysts. RESULTS: The proportions of the six locations were as follows: upside
      45.1% (n = 73), separate 13.0% (n = 21), medial 5.6% (n = 9), lateral 14.2% (n =
      23), in-between 7.4% (n = 12), and unevaluable 14.8% (n = 24). The proportion of
      the cases with a potential risk of infraorbital nerve damage during endoscopic
      marsupialization, including medial, in-between, and unevaluable locations, was
      27.8%. Retrospective chart review revealed that 2 patients with a postoperative
      maxillary cyst that were unevaluable complained of persistent postoperative
      hypoesthesia of the cheek. CONCLUSION: The anatomical relationship between the
      infraorbital nerve and postoperative maxillary cysts varied among patients, with
      approximately one-fourth of the patients being at risk of infraorbital nerve
      injury even during endoscopic procedures.

PMID- 29462812
TI  - Survival Rate without Brain Abnormalities on Postnatal Ultrasonography among
      Monochorionic Twins after Fetoscopic Laser Photocoagulation for Selective
      Intrauterine Growth Restriction with Concomitant Oligohydramnios.
AB  - INTRODUCTION: We aimed to clarify the survival rate without brain abnormalities
      (BA) after fetoscopic laser photoco-agulation (FLP) for monochorionic diamniotic
      twin gestations (MCDA) with selective intrauterine growth restriction (sIUGR)
      accompanied by abnormal umbilical artery (UA) Doppler waveforms and isolated
      oligohydramnios in the sIUGR twin. MATERIALS AND METHODS: This retrospective
      study included 52 cases that underwent FLP. The main outcome was survival rate
      without BA of the twins at age 28 days. BA was defined as severe intraventricular
      hemorrhage and periventricular leukomalacia on postnatal ultrasonography.
      RESULTS: Median gestational age at FLP was 20 (16-24) weeks. Ten cases were
      classified as type III based on Doppler for the UA. For all cases, including 20
      cases of anterior placenta, FLP was completed without major intraoperative
      complications. Amnioinfusion was required in 49 cases for better fetoscopic
      visualization. Fetal loss occurred in 29 sIUGR twins and two larger twins,
      whereas one larger twin experienced neonatal death. Survival rates without BA
      were 44% (n = 23) for sIUGR twins and 94% (n = 49) for the larger twins.
      DISCUSSION: FLP for MCDA with sIUGR presenting with oligohydramnios in the sIUGR
      twin might be considered a prenatal treatment option.

PMID- 29462813
TI  - Hemostatic Efficacy and Safety of the Novel Medical Adhesive, MAR VIVO-107, in a
      Rabbit Liver Resection Model.
AB  - BACKGROUND: Topical hemostatic agents are useful when hepatic hemorrhage is
      difficult to control. The aim of this study was to evaluate the hemostatic
      efficacy and safety of a biodegradable polyurethane-based adhesive, MAR VIVO-107
      (MAR), in comparison with a clinically used fibrin glue. METHODS: Thirty female
      New Zealand white rabbits were randomly assigned to 3 study groups as follows:
      MAR (n = 10), fibrin glue (n = 10), and saline groups (n = 10). After
      standardized partial liver resection was performed, each agent was immediately
      applied to the wound area. Bleeding time until hemostasis and blood loss were
      recorded. After 7 days, body weight, hematology parameters, and serum levels of
      aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase
      were measured. Simultaneously, the severity of intra-abdominal adhesion was
      evaluated. RESULTS: The mean bleeding time in the MAR (38 +/- 10 s) and fibrin
      glue groups (65 +/- 17 s) was significantly shorter than that in the saline group
      (186 +/- 12 s). Similarly, the mean blood loss in the MAR (9 +/- 3 g) and fibrin
      glue groups (9 +/- 3 g) was significantly less than that in the saline group (23
      +/- 4 g). No significant differences in bleeding time and blood loss were found
      between the MAR and fibrin glue groups. The postoperative survival rate was 100%
      in all the groups. Body weight as well as hematological and serum biochemical
      values on day 7 were within the small and physiological range when compared with
      the preoperative baseline values, and significant differences were not detected
      among the MAR, fibrin glue, and saline groups. The severities of adhesion were
      similar between the 3 groups. CONCLUSION: Our data demonstrated that MAR was not
      inferior to fibrin glue in terms of hemostatic efficacy and safety.

PMID- 29462814
TI  - Generalizability of Findings from a Randomized Controlled Trial of Fish Oil
      Supplementation for Attenuating Posttraumatic Stress Symptoms among Rescue
      Workers in Japan.

PMID- 29462815
TI  - A Trend in Sudden Sensorineural Hearing Loss: Data from a Population-Based Study.
AB  - This is the first study reporting on the incidence and clinical aspects of sudden
      sensorineural hearing loss (SSNHL) in South Korea. Using Health Insurance Review
      and Assessment Service data from 2011 to 2015, the monthly incidence of
      unilateral SSNHL and incidence according to patients' sex, age, and month of
      diagnosis were investigated. The monthly incidence of unilateral SSNHL increased
      over the 5-year study period, with a mean annual incidence of 17.76 cases/
      100,000 of the population. The incidence increased with age, with most patients
      presenting in their 60s. There was a slight female preponderance, with a male-to
      female ratio of 1: 1.35. Most new patients were diagnosed in October, and the
      fewest in January. In conclusion, this large-scale study indicates that
      unilateral SSNHL has a higher incidence among the elderly, women, and in autumn
      (i.e., along with colder weather).

PMID- 29462816
TI  - Relapse and Recurrence of Common Mental Health Problems after Low Intensity
      Cognitive Behavioural Therapy: The WYLOW Longitudinal Cohort Study.

PMID- 29462817
TI  - The Interaction of N-Acetylcysteine and Serum Transferrin Promotes Bacterial
      Biofilm Formation.
AB  - BACKGROUND/AIMS: N-acetylcysteine (NAC) is a novel and promising agent with
      activity against bacterial biofilms. Human serum also inhibits biofilm formation
      by some bacteria. We tested whether the combination of NAC and human serum offers
      greater anti-biofilm activity than either agent alone. METHODS: Microtiter plate
      assays and confocal laser scanning microscopy were used to evaluate bacterial
      biofilm formation in the presence of NAC and human serum. qPCR was used to
      examine expression of selected biofilm-associated genes. Extracellular matrix
      (ECM) was observed by transmission electron microscopy. The antioxidants GSH or
      ascorbic acid were used to replace NAC, and human transferrin, lactoferrin, or
      bovine serum albumin were used to replace serum proteins in biofilm formation
      assays. A rat central venous catheter model was developed to evaluate the effect
      of NAC on biofilm formation in vivo. RESULTS: NAC and serum together increased
      biofilm formation by seven different bacterial strains. In Staphylococcus aureus,
      expression of genes for some global regulators and for genes in the ica-dependent
      pathway increased markedly. In Pseudomonas aeruginosa, transcription of las, the
      PQS quorum sensing (QS) systems, and the two-component system GacS/GacA increased
      significantly. ECM production by S. aureus and P. aeruginosa was also enhanced.
      The potentiation of biofilm formation is due mainly to interaction between NAC
      and transferrin. Intravenous administration of NAC increased colonization by S.
      aureus and P. aeruginosa on implanted catheters. CONCLUSIONS: NAC used
      intravenously or in the presence of blood increases bacterial biofilm formation
      rather than inhibits it.

PMID- 29462818
TI  - Effects of MicroRNA-206 on Osteosarcoma Cell Proliferation, Apoptosis, Migration
      and Invasion by Targeting ANXA2 Through the AKT Signaling Pathway.
AB  - BACKGROUND/AIMS: This study aimed to investigate the mechanism by which microRNA
      206 (miR-206) affects the proliferation, apoptosis, migration and invasion of
      osteosarcoma (OS) cells by targeting ANXA2 via the AKT signaling pathway.
      METHODS: A total of 132 OS tissues and 120 osteochondroma tissues were examined
      in this study. The targeting relationship between miR-206 and ANXA2 was verified
      with a dual-luciferase reporter assay. The miR-206 expression and ANXA2, AKT,
      PARP, FASN, Survivin, Bax, Mcl-1 and Bcl-1 mRNA and protein expression in the
      above two groups were examined by qRT-PCR and western blotting. The cultured OS
      cells were divided into 6 groups: a blank group, negative control (NC) group, miR
      206 mimic group, miR-206 inhibitor group, si-ANXA2 group and miR-206 inhibitor +
      si-ANXA2 group. Cell cycle and apoptosis were assessed by flow cytometry, cell
      migration was examined with a wound-healing assay, and cell invasion was assessed
      with a Transwell assay. Pearson correlation analysis was used to determine the
      correlation between ANXA2 mRNA expression and miR-206 expression in OS. RESULTS:
      OS tissues exhibited increased mRNA and protein expression of ANXA2, AKT, PARP,
      FASN, Survivin, Mcl-1 and Bcl-2; decreased miR-206 expression; and decreased Bax
      mRNA and protein expression. ANXA2 mRNA expression was strongly negatively
      correlated with miR-206 expression in OS. ANXA2 was found to be a miR-206 target
      gene. In the miR-206 mimic group and the si-ANXA2 group, the mRNA and protein
      expression of ANXA2, AKT, PARP, FASN, Survivin, Mcl-1 and Bcl-1 decreased
      markedly, cell proliferation was inhibited, apoptosis was promoted, higher cell
      growth in G1 phase and decreased growth in S phase was detected, and decreased
      cell migration and invasion were observed compared with those in the blank group.
      CONCLUSION: The current results demonstrate that miR-206 overexpression inhibits
      OS cell proliferation, migration and invasion and promotes apoptosis through
      targeting ANXA2 by blocking the AKT signaling pathway.

PMID- 29462819
TI  - Low-Dose Aspirin for Prevention of Cardiovascular Risk in Bereavement: Results
      from a Feasibility Study.

PMID- 29462820
TI  - Comment on: Higher Rates of Operative Delivery and Maternal and Neonatal
      Complications in Persistent Occiput Posterior Position with a Large Head
      Circumference: A Retrospective Cohort Study.

PMID- 29462821
TI  - The Topography of Stuttering in Cantonese.
AB  - OBJECTIVE: This is the first study to investigate the behavioral nature
      (topography) of stuttering in Cantonese. Cantonese, a Sino-Tibetan language, is
      both tonal and syllable-timed. Previous studies of stuttering topography have
      mainly been in Western languages, which are mainly stress-timed. METHODS:
      Conversational speech samples were collected from 24 native Cantonese-speaking
      adults who stuttered. Six consecutive stuttering moments from each participant
      were analyzed using the Lidcombe behavioral data language (LBDL). A complexity
      analysis based on the LBDL was developed to indicate the proportion of multiple
      behavior stuttering moments for each participant. RESULTS: There was no
      significant difference in the frequency of the 7 LBDL behaviors. Almost half the
      stuttering moments across participants were reported as complex, containing more
      than 1 stuttering behavior, and stuttering complexity correlated significantly
      with stuttering severity. CONCLUSIONS: These preliminary findings require
      replication because of their important theoretical and clinical implications.
      Differences in topography across languages have the potential to contribute to
      our understanding of the nature of stuttering. Clinically, the recognition of
      such differences may assist practitioners in identifying stuttering, for example
      when screening for early stuttering. The LBDL complexity score developed in this
      study has the potential to be used in other languages.

PMID- 29462822
TI  - Vocal Fry and Vowel Height in Simulated Room Acoustics.
AB  - PURPOSE: The purpose of this study was to investigate the influence of room
      acoustics in the relationship between vowel height and vocal fry. METHODS: This
      was a cross-sectional study. Participants (college students, n = 40) read the
      first six sentences of "The Rainbow Passage" under nine simulated room acoustic
      conditions. Using two words with low vowels (act, pot) and two words with high
      vowels (shape, strikes) preceding a voiceless stop, the presence/absence of vocal
      fry was assessed using an automatic detection script. Generalized estimation
      equations were used to investigate the relationship between percentage of vocal
      fry, vowel height, and room acoustics. RESULTS: The percentage of vocal fry was
      significantly higher for the low-height vowels compared with the high-height
      vowels (beta = 1.21; standard er ror = 0.35), and for pink background noise
      present (beta = 0.89; standard error = 0.35) compared with the condition without
      artificial noise added. CONCLUSION: The results of this study indicate that young
      college students are more likely to produce fry phonation when producing low
      height vowels under pink background noise condition compared with no noise
      conditions and high-height vowels. This result is of special interest for voice
      clinicians when designing therapy plans and vocal assessment protocols with fry
      like components.

PMID- 29462823
TI  - Early Psychological Counseling for the Prevention of Posttraumatic Stress Induced
      by Acute Coronary Syndrome: The MI-SPRINT Randomized Controlled Trial.
AB  - BACKGROUND: Acute coronary syndrome (ACS)-induced posttraumatic stress disorder
      (PTSD) and clinically significant PTSD symptoms (PTSS) are found in 4 and 12% of
      patients, respectively. We hypothesized that trauma-focused counseling prevents
      the incidence of ACS-induced PTSS. METHODS: Within 48 h of hospital admission,
      190 patients with high distress during ACS were randomized to a single-session
      intervention of either trauma-focused counseling or an active control
      intervention targeting the general role of stress in patients with heart disease.
      Blind interviewer-rated PTSS (primary outcome) and additional health outcomes
      were assessed at 3 months of follow-up. Trial results about prevalence were
      compared with data from previous studies on the natural incidence of ACS-induced
      PTSS/PTSD. RESULTS: Intention-to-treat analyses revealed no difference in
      interviewer-rated PTSS between trauma-focused counseling (mean, 11.33; 95% Cl,
      9.23-13.43) and stress counseling (9.88; 7.36-12.40; p = 0.40), depressive
      symptoms (6.01, 4.98-7.03, vs. 4.71, 3.65-5.77; p = 0.08), global psychological
      distress (5.15, 4.07-6.23, vs. 3.80, 2.60-5.00; p = 0.11), and the risk for
      cardiovascular-related hospitalization/all-cause mortality (OR, 0.67; 95% CI,
      0.37-1.23). Self-rated PTSS indicated less beneficial effects with trauma-focused
      (6.54; 4.95-8.14) versus stress counseling (3.74; 2.39-5.08; p = 0.017). The
      completer analysis (154 cases) confirmed these findings. The prevalence rates of
      interviewer-rated PTSD (0.5%, 1/190) and self-rated PTSS were in this trial much
      lower than in meta-analyses and observation studies from the same cardiology
      department. CONCLUSIONS: Benefits were not seen for trauma-focused counseling
      when compared with an active control intervention. Nonetheless, in distressed ACS
      patients, individual, single-session, early psychological counseling shows
      potential as a means to prevent posttraumatic responses, but trauma-focused early
      treatments should probably be avoided.

PMID- 29462824
TI  - The "Auto-sliding Graft" Aortic Wrapping Technique.
AB  - We describe the "auto-sliding graft" technique, a different anastomotic option
      for reconstructive prosthetic procedures on the ascending aorta especially in
      patients at risk of circulatory arrest with mild aortic dilatation. This simple
      technique provides not only an important hemostatic reinforcement for the distal
      aortic graft anastomosis but also a protective effect on the native ascending
      aorta beyond the suture line.

PMID- 29462825
TI  - Golgi Fragmentation in Human Patients with Chronic Atrial Fibrillation: A New
      Aspect of Remodeling.
AB  - BACKGROUND:  Atrial fibrillation (AF) is the most common chronic arrhythmia in
      elderly people and is accompanied by remodeling processes. While much is known
      about changes in ionic channels and in extracellular matrix, less is known about
      possible changes of intracellular structures. OBJECTIVE:  We wanted to
      investigate, whether AF may also affect the structure of the Golgi apparatus and
      the microtubular network. METHODS:  One-hundred fifty-three cardiac surgery
      patients were investigated [n = 24 in sinus rhythm (SR) and n = 129 with chronic
      AF of >1 year duration]. Tissue samples of the left atrial free wall were
      examined immunohistochemically. Golgi apparatus was detected by GM130 and its
      phosphorylated isoform. Furthermore, we investigated the length of the
      microtubules by alpha-tubulin staining. We also measured stathmin (phospho-S37),
      which is known to induce microtubule depolymerization. In addition, we
      investigated the cyclin-dependent kinase cdk5-activation, a typical stimulus for
      Golgi fragmentation, by measuring membrane-associated cdk5. RESULTS:  We found
      significant fragmentation of the Golgi apparatus in AF together with a reduced
      fragment size. Significant more fragments of the Golgi were found lateral to the
      nucleus in AF, while the Golgi in SR was located more to the polar side of the
      nucleus, that is, in the longitudinal axis of the cell. This was accompanied by a
      significant reduction of the number of tubulin strands longer than 10 um. These
      changes did not go along with an activation of stathmin, but with an increase in
      membrane association of cdk5. CONCLUSIONS:  The present data may show that AF
      associated remodeling also involves intracellular remodeling of the Golgi
      microtubular apparatus.

PMID- 29462826
TI  - Graft-Sparing Strategy for Thoracic Prosthetic Graft Infection.
AB  - OBJECTIVE: Thoracic prosthetic graft infection is a rare but serious complication
      with no standard management. We reported our surgical experience on graft-sparing
      strategy for thoracic prosthetic graft infection. METHODS: This study included
      patients who underwent graft-sparing surgery for thoracic prosthetic graft
      infection at Matsubara Tokushukai Hospital in Japan from January 2000 to October
      2017. RESULTS: There were 17 patients included in the analyses, with a mean age
      at surgery of 71.0 +/- 10.5 years; 11 were men. In-hospital mortality was
      observed in five patients (29.4%). CONCLUSIONS: Graft-sparing surgery for
      thoracic prosthetic graft infection is an alternative option particularly for
      early graft infection after hemiarch replacement.

PMID- 29462827
TI  - Which is the Best Minimal Invasive Approach for the Treatment of Spontaneous
      Pneumothorax? Uniport, Two, or Three Ports: A Prospective Randomized Trail.
AB  - OBJECTIVE: Video-assisted thoracoscopic surgery (VATS) has become the standard
      treatment method for primary spontaneous pneumothorax. Concerns about lesser pain
      and better cosmesis led to the evolution of uniportal access. This study
      prospectively compared the results of the uniportal, two-port, and three-port
      thoracoscopic surgery. MATERIAL AND METHODS: One hundred and thirty-five patients
      were randomized into three groups according to the port numbers. The groups were
      compared regarding the operation time, hospital stay, amount of drainage, area of
      pleurectomy, complications, recurrences, and pain scores. RESULTS: Except for the
      amount of drainage (p = 0.03), no factors were found to be statistically
      significant. The overall recurrence rate was 5%. Although the first and second
      week pain scores were not statistically significant, the single-incision group
      patients had significantly less pain at 4, 24, and 72 hours (p < 0.05).
      CONCLUSION: The study indicated that uniportal VATS approach is less painful and
      has better cosmetic results, besides it is as efficient as two- or three-port
      VATS approach.

PMID- 29462828
TI  - Computer-Aided Surgical Simulation in Head and Neck Reconstruction: A Cost
      Comparison among Traditional, In-House, and Commercial Options.
AB  - BACKGROUND:  Computer-aided surgical simulation (CASS) has redefined surgery,
      improved precision and reduced the reliance on intraoperative trial-and-error
      manipulations. CASS is provided by third-party services; however, it may be cost
      effective for some hospitals to develop in-house programs. This study provides
      the first cost analysis comparison among traditional (no CASS), commercial CASS,
      and in-house CASS for head and neck reconstruction. METHODS:  The costs of three
      dimensional (3D) pre-operative planning for mandibular and maxillary
      reconstructions were obtained from an in-house CASS program at our large tertiary
      care hospital in Northern Virginia, as well as a commercial provider (Synthes,
      Paoli, PA). A cost comparison was performed among these modalities and
      extrapolated in-house CASS costs were derived. The calculations were based on
      estimated CASS use with cost structures similar to our institution and sunk costs
      were amortized over 10 years. RESULTS:  Average operating room time was estimated
      at 10 hours, with an average of 2 hours saved with CASS. The hourly cost to the
      hospital for the operating room (including anesthesia and other ancillary costs)
      was estimated at $4,614/hour. Per case, traditional cases were $46,140,
      commercial CASS cases were $40,951, and in-house CASS cases were $38,212. Annual
      in-house CASS costs were $39,590. CONCLUSIONS:  CASS reduced operating room time,
      likely due to improved efficiency and accuracy. Our data demonstrate that
      hospitals with similar cost structure as ours, performing greater than 27 cases
      of 3D head and neck reconstructions per year can see a financial benefit from
      developing an in-house CASS program.

PMID- 29462829
TI  - [Evaluation of velopharyngeal closing pressure during trumpet play with high
      resolution manometry].
AB  - OBJECTIVE: In about one-third of brass instrumentalists, there are stress-related
      insufficiencies of velopharyngeal closure (VPC), i. e. the intraoral pressure
      exceeds the barrier formed by the VPC. Here, it was the aim to measure the VPC
      closing pressure while playing a trumpet and to evaluate the influence of a 30
      minute stress sequence on the muscular activities in the VPC. MATERIAL AND
      METHODS: Sample: 6 healthy volunteers; task: to play the sound h1 for 5 seconds
      with 85 dB(A) and with 100 dB(A). METHODOLOGY: High-resolution manometry (HRM).
      SAMPLING: t0: measurement without warm up phase t1 after 30 min trumpet play;
      practice phase with predefined pieces of music. VARIABLES: mean (pmit), minimum
      (pmin) and maximum pressure (pmax) in the VPA at t0 and t1. STATISTICS: testing
      for normal distribution, t-test. RESULTS: All measured pressures in the VPC
      decreased from t0 to t1 for tones produced at 85 dB(A). For 100 dB(A) tones only
      the pmin decreased significantly. The pressures in the VPA were higher at 100
      dB(A) tones overall compared to 85 dB(A) tones, significant differences were
      found for pmin and pmax at t0. CONCLUSION: Tones played at louder volumes require
      a stronger muscular contraction in the VPC. The lower VPC pressure after the
      exercise phase (t1) can either result from a physiological muscular adaptation to
      the pressure level necessary for a sufficient VPC or already be a sign of
      muscular fatigue. These findings may be important to assess the work ability of
      wind instrumentalists by HRM. As shown for the phonation, the VPC pressure
      profile for the trumpet play can also be described with a three-phase model
      consisting of an initiation, a stable phase and a termination.

PMID- 29462830
TI  - [Quo Vadis Data Linkage in Germany? An Initial Inventory].
AB  - In recent years, linking different data sources, also called data linkage or
      record linkage, to address scientific questions, is being increasingly used in
      Germany. However, there are very few published reports and new projects develop
      the necessary tools independently of each other. Therefore, a team of researchers
      joined together to exchange their experiences on data linkage and to give
      suggestions on how linkage could be done for scientists, reviewers as well as
      members of data privacy boards and ethics committees. It is the aim of this
      article to assist future projects that want to link German data on an individual
      level. In addition to the legal framework conditions (data privacy), also
      examples of types of data linkage, their fields of application und potential
      pitfalls as well as the methods of preventing them will be described in an
      application-oriented fashion.

PMID- 29462831
TI  - ?

PMID- 29462832
TI  - [Pulmonary Medicine and its Institutions During National Socialism].
AB  - When the National Socialists came to power in 1933, a complete paradigm shift
      took place in the health policy under the principle "Public interest ahead of
      self-interest". In the early years there was an intense discussion about whether
      tuberculosis (TB) is more caused by heredity or by infection. Finally, the
      arguments of leading TB specialists were accepted that TB is predominantly an
      infectious disease. In 1939, the year Germany started World War II, TB mortality
      was at its lowest, with only a few countries having lower rates. TB mortality
      increased in all areas during the war, both in the civilian population and in the
      Wehrmacht, as well as in prisoners of war, foreign forced laborers and
      concentration camps. Incapable TB patients were considered biological and social
      "ballast". They were worthless for the "national community" and had to be
      socially excluded. Thus one could refuse them the "marriage loan" introduced in
      the summer 1933, forbid starting from 1935 also the marriage. From 1938 on, TB
      patients with open TB, who showed themselves unreasonable, could be compulsorily
      isolated as "asocial" by public health physicians - mostly pulmonary specialists.
      There, under prison conditions and with limited food, most patients fell victim
      to TB in a short time. Especially inhuman was the handling of prisoners in the
      concentration camps, where the disease was very common. Thousands of people were
      killed prematurely through deliberate neglect, starvation, abuse for medical
      experiments, or simply murdered. TB mortality increased by 160 - 240 % compared
      to pre-war levels. With the support of the victorious Allied powers, the TB
      control system was restructured and the institutions such as DGP and DZK were re
      established. In the following years, the TB situation improved slowly, in the FRG
      initially slightly faster than in the GDR.

PMID- 29462833
TI  - Multilevel moderated mediation model with ordinal outcome.
AB  - Although increasingly complex models have been proposed in mediation literature,
      there is no model nor software that incorporates the multiple possible
      generalizations of the simple mediation model jointly. We propose a flexible
      moderated mediation model allowing for (1) a hierarchical structure of clustered
      data, (2) more and possibly correlated mediators, and (3) an ordinal outcome. The
      motivating data set is obtained from a European study in nursing research.
      Patients' willingness to recommend their treating hospital was recorded in an
      ordinal way. The research question is whether such recommendation directly
      depends on system-level features in the organization of nursing care, or whether
      these associations are mediated by 2 measurements of nursing care left undone and
      possibly moderated by nurse education. We have developed a Bayesian approach and
      accompanying program that takes all the above generalizations into account.

PMID- 29462834
TI  - Cost-effectiveness of a chronic disease management model for cirrhosis: Analysis
      of a randomized controlled trial.
AB  - BACKGROUND AND AIMS: In this follow-up study to a randomized controlled trial of
      a chronic disease management (CDM) model in cirrhosis, our aim was to assess the
      relative cost-effectiveness of this model compared with usual care during the 12
      month study period, using incremental costs per death avoided as the primary
      outcome. METHODS: Mean differences in hospitalization costs, deaths avoided, and
      change in Chronic Liver Disease Questionnaire (CLDQ) total scores were presented
      with 95% non-parametric bootstrapped confidence intervals. Results were also
      presented using a cost-effectiveness plane (CEP) and cost-effectiveness
      acceptability curve. RESULTS: The CDM intervention was more expensive, by 18 521
      AUD per participant, but more effective (% of deaths at 12 months: 10% vs 15% and
      0.67 units increase per patient in CLDQ total scores). The resultant incremental
      cost-effectiveness ratios were 370 425 AUD per death avoided (95% confidence
      interval: -14 564 AUD to 2 059 373 AUD) and 27 547 AUD per unit improvement in
      the CLDQ total score (95% CI: 7455 AUD to 143 874 AUD). The CEPs demonstrated
      some uncertainty around cost-effectiveness. The cost-effectiveness acceptability
      curves demonstrated that at willingness to pay values of 400 000 AUD per
      additional death avoided and 40 000 AUD per unit improvement in the CLDQ, there
      was at least a 70% probability of CDM being more cost-effective than usual care.
      At 24 months, CDM was much more effective (12% less deaths but now also cheaper
      by 985 AUD per patient). CONCLUSIONS: The analysis of data from a randomized
      controlled trial suggests that the CDM intervention used is likely to be cost
      effective, relative to usual care, due to fewer patient deaths.

PMID- 29462835
TI  - Controlling the type I error rate in two-stage sequential adaptive designs when
      testing for average bioequivalence.
AB  - In a 2*2 crossover trial for establishing average bioequivalence (ABE) of a
      generic agent and a currently marketed drug, the recommended approach to
      hypothesis testing is the two one-sided test (TOST) procedure, which depends,
      among other things, on the estimated within-subject variability. The power of
      this procedure, and therefore the sample size required to achieve a minimum
      power, depends on having a good estimate of this variability. When there is
      uncertainty, it is advisable to plan the design in two stages, with an interim
      sample size reestimation after the first stage, using an interim estimate of the
      within-subject variability. One method and 3 variations of doing this were
      proposed by Potvin et al. Using simulation, the operating characteristics,
      including the empirical type I error rate, of the 4 variations (called Methods A,
      B, C, and D) were assessed by Potvin et al and Methods B and C were recommended.
      However, none of these 4 variations formally controls the type I error rate of
      falsely claiming ABE, even though the amount of inflation produced by Method C
      was considered acceptable. A major disadvantage of assessing type I error rate
      inflation using simulation is that unless all possible scenarios for the intended
      design and analysis are investigated, it is impossible to be sure that the type I
      error rate is controlled. Here, we propose an alternative, principled method of
      sample size reestimation that is guaranteed to control the type I error rate at
      any given significance level. This method uses a new version of the inverse
      normal combination of p-values test, in conjunction with standard group
      sequential techniques, that is more robust to large deviations in initial
      assumptions regarding the variability of the pharmacokinetic endpoints. The
      sample size reestimation step is based on significance levels and power
      requirements that are conditional on the first-stage results. This necessitates a
      discussion and exploitation of the peculiar properties of the power curve of the
      TOST testing procedure. We illustrate our approach with an example based on a
      real ABE study and compare the operating characteristics of our proposed method
      with those of Method B of Povin et al.

PMID- 29462836
TI  - Current practice for genetic counselling by nurses: An integrative review.
AB  - AIM: To examine current practice of genetic counselling by nurses. BACKGROUND:
      Recent debate argues that genetic counselling is a specialist advanced practice
      role, whilst others argue it is the role of all nurses. Current evidence is
      required to determine if genetic counselling could be included in all nurses'
      scope of practice. DESIGN: Integrative literature review. DATA SOURCES: A search
      of electronic databases (CINHAL, Medline, PubMed, Scopus), and reference lists
      published between January 2012 and March 2017, was undertaken. REVIEW METHODS:
      Studies were critically appraised for methodological quality using the Critical
      Appraisal Skills Programme. Data from each study were extracted and categorized
      according to their primary findings. RESULTS: The inclusion criteria were met in
      10 studies. Main findings were identified: role of genetic counselling, current
      knowledge, need for further education, and client satisfaction with nurse genetic
      counsellors. CONCLUSION: This paper concludes that some nurses do engage in
      genetic counselling, but how they engage is not consistent, nor is there
      consensus about what should be the scope of practice. Further investigation into
      credentialing, role recognition support and education for nurse genetic
      counselling are strongly recommended. As nurses are widely available, nurses can
      make a significant contribution to supporting those affected by genetic problems.

PMID- 29462837
TI  - Reduced arterial vasodilatation in response to hypoxia impairs cerebral and
      peripheral oxygen delivery in hypertensive men.
AB  - KEY POINTS: Hypoxaemia evokes a repertoire of homeostatic adjustments that
      maintain oxygen supply to organs and tissues including the brain and skeletal
      muscles. Because hypertensive patients have impaired endothelial-dependent
      vasodilatation and an increased sympathetic response to arterial oxygen
      desaturation, we investigated whether hypertension impairs isocapnic hypoxia
      induced cerebral and skeletal muscle hyperaemia to an extent that limits oxygen
      supply. In middle-aged hypertensive men, vertebral and femoral artery blood flow
      do not increase in response to isocapnic hypoxia, limiting brain and peripheral
      hyperaemia and oxygen supply. Increased chemoreflex-induced sympathetic
      activation impairs skeletal muscle perfusion and oxygen supply, whereas an
      attenuation of local vasodilatory signalling in the posterior cerebrovasculature
      reduced brain hyperperfusion of hypertensive middle-aged men in response to
      isocapnic hypoxia. ABSTRACT: The present study investigated whether hypertension
      impairs isocapnic hypoxia (IH)-induced cerebral and skeletal muscle hyperaemia to
      an extent that limits oxygen supply. Oxygen saturation (oxymetry), mean arterial
      pressure (photoplethysmography) and muscle sympathetic nerve activity (MSNA;
      microneugraphy), as well as femoral artery (FA), internal carotid artery and
      vertebral artery (VA) blood flow (BF; Doppler ultrasound), were quantified in
      nine normotensive (NT) (aged 40 +/- 11 years, systolic pressure 119 +/- 7 mmHg
      and diastolic pressure 73 +/- 6 mmHg) and nine hypertensive men (HT) (aged 44 +/-
      12 years, systolic pressure 152 +/- 11 mmHg and diastolic pressure 90 +/- 9 mmHg)
      during 5 min of normoxia (21% O2 ) and IH (10% O2 ). Total cerebral blood flow
      (tCBF), brain (CDO2 ) and leg (LDO2 ) oxygen delivery were estimated. IH provoked
      similar oxygen desaturation without changing mean arterial pressure. Internal
      carotid artery perfusion increased in both groups during IH. However, VA and FA
      BF only increased in NT. Thus, IH-induced increase in tCBF was smaller in HT.
      CDO2 only increased in NT and LDO2 decreased in HT. Furthermore, IH evoked a
      greater increase in HT MSNA. Changes in MSNA were inversely related to FA BF,
      LDO2 and end-tidal oxygen tension. In conclusion, hypertension disturbs regional
      and total cerebrovascular and peripheral responses to IH and consequently limits
      oxygen supply to the brain and skeletal muscle. Although increased chemoreflex
      induced sympathetic activation may explain impaired peripheral perfusion,
      attenuated vasodilatory signalling in the posterior cerebrovasculature appears to
      be responsible for the small increase in tCBF when HT were exposed to IH.

PMID- 29462838
TI  - Sequential parallel comparison design with binary and time-to-event outcomes.
AB  - Sequential parallel comparison design (SPCD) has been proposed to increase the
      likelihood of success of clinical trials especially trials with possibly high
      placebo effect. Sequential parallel comparison design is conducted with 2 stages.
      Participants are randomized between active therapy and placebo in stage 1. Then,
      stage 1 placebo nonresponders are rerandomized between active therapy and
      placebo. Data from the 2 stages are pooled to yield a single P value. We consider
      SPCD with binary and with time-to-event outcomes. For time-to-event outcomes,
      response is defined as a favorable event prior to the end of follow-up for a
      given stage of SPCD. We show that for these cases, the usual test statistics from
      stages 1 and 2 are asymptotically normal and uncorrelated under the null
      hypothesis, leading to a straightforward combined testing procedure. In addition,
      we show that the estimators of the treatment effects from the 2 stages are
      asymptotically normal and uncorrelated under the null and alternative hypothesis,
      yielding confidence interval procedures with correct coverage. Simulations and
      real data analysis demonstrate the utility of the binary and time-to-event SPCD.

PMID- 29462839
TI  - Sensitivity analysis for unobserved confounding of direct and indirect effects
      using uncertainty intervals.
AB  - To estimate direct and indirect effects of an exposure on an outcome from
      observed data, strong assumptions about unconfoundedness are required. Since
      these assumptions cannot be tested using the observed data, a mediation analysis
      should always be accompanied by a sensitivity analysis of the resulting
      estimates. In this article, we propose a sensitivity analysis method for
      parametric estimation of direct and indirect effects when the exposure, mediator,
      and outcome are all binary. The sensitivity parameters consist of the
      correlations between the error terms of the exposure, mediator, and outcome
      models. These correlations are incorporated into the estimation of the model
      parameters and identification sets are then obtained for the direct and indirect
      effects for a range of plausible correlation values. We take the sampling
      variability into account through the construction of uncertainty intervals. The
      proposed method is able to assess sensitivity to both mediator-outcome
      confounding and confounding involving the exposure. To illustrate the method, we
      apply it to a mediation study based on the data from the Swedish Stroke Register
      (Riksstroke). An R package that implements the proposed method is available.

PMID- 29462840
TI  - A Bayesian semiparametric Markov regression model for juvenile dermatomyositis.
AB  - Juvenile dermatomyositis (JDM) is a rare autoimmune disease that may lead to
      serious complications, even to death. We develop a 2-state Markov regression
      model in a Bayesian framework to characterise disease progression in JDM over
      time and gain a better understanding of the factors influencing disease risk. The
      transition probabilities between disease and remission state (and vice versa) are
      a function of time-homogeneous and time-varying covariates. These latter types of
      covariates are introduced in the model through a latent health state function,
      which describes patient-specific health over time and accounts for variability
      among patients. We assume a nonparametric prior based on the Dirichlet process to
      model the health state function and the baseline transition intensities between
      disease and remission state and vice versa. The Dirichlet process induces a
      clustering of the patients in homogeneous risk groups. To highlight clinical
      variables that most affect the transition probabilities, we perform variable
      selection using spike and slab prior distributions. Posterior inference is
      performed through Markov chain Monte Carlo methods. Data were made available from
      the UK JDM Cohort and Biomarker Study and Repository, hosted at the UCL Institute
      of Child Health.

PMID- 29462841
TI  - Caring about dying persons and their families: Interpretation, practice and
      emotional labour.
AB  - The importance of emotional support for dying persons and their families has been
      well established, yet we know less about how care workers understand emotional
      processes related to death and dying, or how these understandings are connected
      to care practices and emotional labour at the end of life. The aim of this study
      was to explore how healthcare workers interpret and respond to emotional needs of
      dying persons and their families. Qualitative data were collected between 2013
      and 2014 through in-depth, in-person interviews with 14 nurses and 12 healthcare
      aides in one Western Canadian city. Transcripts were analysed using an inductive,
      interpretive thematic coding approach and the analytic lens of emotional labour.
      Dominant interpretive frames of a "good death" informed participants' emotionally
      supportive practice. This included guiding patients and families to "open up"
      about their emotions to activate the grief process. There was concern that
      incomplete grieving would result in anger being directed towards care staff. The
      goal of promoting emotional sharing informed the work of "caring about." Although
      palliative philosophies opened up moral and professional space for "caring about"
      in the context of organisational norms which often discouraged these practices,
      the tension between the two, and the lack of time for this work, may encourage
      surface expressions rather than authentic emotional care.

PMID- 29462842
TI  - Hyperinflation of bronchi in vitro impairs bronchodilation to simulated breathing
      and increases sensitivity to contractile activation.
AB  - BACKGROUND AND OBJECTIVE: Lung hyperinflation and reduced bronchodilation to deep
      inspiration (DI) are features of chronic obstructive pulmonary disease (COPD).
      Hyperinflation might impair the ability of a DI to stretch airway smooth muscle
      (ASM), as the bronchi operate at a stiff region of the pressure-volume curve.
      METHODS: Bronchial segments from pig lungs were mounted in an organ bath and
      equilibrated at either 5 cm H2 O (control) or 20 cm H2 O (hyperinflated)
      transmural pressure (Ptm ). Cumulative dose-response curves to acetylcholine
      (ACh) were performed to determine maximal response (Emax ) and sensitivity under
      static conditions (fixed Ptm ) or during simulated breathing (Delta10 cm H2 O Ptm
      at 0.25 Hz). The effect of hyperinflation on ASM contraction was further examined
      in bronchial rings contracted at a short ASM length (reference length, Lref ) or
      stretched by an additional 30% (length 1.3 times the Lref , 1.3Lref ). RESULTS:
      Oscillatory loads halved Emax from 61.0 +/- 3.8 to 29.7 +/- 4.4 cm H2 O (P <
      0.0001) in control bronchial segments, but only from 40.0 +/- 2.5 to 31.2 +/- 2.4
      cm H2 O (P < 0.05) in hyperinflated segments. The percentage reduction in active
      pressure with oscillation was less in hyperinflated compared with control
      segments (P < 0.01). Sensitivity was not altered by oscillation in either
      hyperinflated or control segments; however, hyperinflated segments were more
      sensitive (P < 0.05). The effect of inflation on sensitivity was confirmed using
      bronchial rings where stretched rings were more sensitive than unstretched rings
      (P < 0.01). CONCLUSION: Hyperinflated bronchi exhibit reduced bronchodilation to
      breathing and increased sensitivity to bronchoconstrictor stimuli. Findings
      suggest that hyperinflation may directly alter airway function by reducing the
      protective effects of DI and initiating contraction at low doses of contractile
      stimuli.

PMID- 29462843
TI  - Three-dimensional photography for the evaluation of facial profiles in
      obstructive sleep apnoea.
AB  - BACKGROUND AND OBJECTIVE: Craniofacial structure is an important determinant of
      obstructive sleep apnoea (OSA) syndrome risk. Three-dimensional stereo
      photogrammetry (3dMD) is a novel technique which allows quantification of the
      craniofacial profile. This study compares the facial images of OSA patients
      captured by 3dMD to three-dimensional computed tomography (3-D CT) and two
      dimensional (2-D) digital photogrammetry. Measurements were correlated with
      indices of OSA severity. METHODS: Thirty-eight patients diagnosed with OSA were
      included, and digital photogrammetry, 3dMD and 3-D CT were performed. Distances,
      areas, angles and volumes from the images captured by three methods were
      analysed. RESULTS: Almost all measurements captured by 3dMD showed strong
      agreement with 3-D CT measurements. Results from 2-D digital photogrammetry
      showed poor agreement with 3-D CT. Mandibular width, neck perimeter size and
      maxillary volume measurements correlated well with the severity of OSA using all
      three imaging methods. Mandibular length, facial width, binocular width, neck
      width, cranial base triangle area, cranial base area 1 and middle cranial fossa
      volume correlated well with OSA severity using 3dMD and 3-D CT, but not with 2-D
      digital photogrammetry. CONCLUSION: 3dMD provided accurate craniofacial
      measurements of OSA patients, which were highly concordant with those obtained by
      CT, while avoiding the radiation associated with CT.

PMID- 29462844
TI  - How can we improve the performance of Model for End-Stage Liver Disease sodium
      score in patients with hepatitis B virus-related decompensated liver cirrhosis
      commencing antiviral treatment?
AB  - BACKGROUND AND AIM: We aimed to develop a more efficient prognostic model to
      predict 1-year mortality in patients with hepatitis B virus-related decompensated
      cirrhosis beginning antiviral treatment. METHODS: Using Cox regression analysis,
      survival analyses were performed on 554 patients with decompensated cirrhosis who
      were followed up from the start of nucleos(t)ide analogue antiviral treatment.
      RESULTS: At baseline, ascites and hepatic encephalopathy were found in 78.0% and
      18.1% of patients, respectively. Eighty-six events (77 deaths and 9 emergency
      liver transplants) occurred within the first year of treatment. Severity of
      ascites, presence of hepatic encephalopathy, and the Model for End-Stage Liver
      Disease (MELD)-sodium (MELDNa) score were independent risk factors for 1-year
      mortality. The new prognostic model (the revised MELDNa) constructed by adding
      ascites and encephalopathy to the MELDNa score significantly improved the area
      under the receiver operating characteristics curve for predicting 1-year events
      at baseline compared with the Child-Turcotte-Pugh system, MELD and MELDNa models,
      and Fontana index (0.905 vs 0.867, 0.843, 0.871, and 0.815, respectively; P <
      0.05). Furthermore, repetitive application of revised MELDNa at 0, 1, 2, 3, and 6
      months of treatment could predict 81.4% (70/86) of 1-year events, which was
      significantly (P < 0.05) higher than the sensitivity of the Child-Turcotte-Pugh
      system (68.6%), MELD (70.9%) and MELDNa (68.6%) scores, and Fontana index
      (64.0%), achieving similar specificities of ~96%. CONCLUSIONS: Ascites and
      encephalopathy should be considered together with the MELDNa score when
      predicting short-term mortality and planning liver transplant in patients with
      decompensated hepatitis B virus-related cirrhosis starting antiviral treatment.

PMID- 29462845
TI  - Comparison of the microbial community structure between inflamed and non-inflamed
      sites in patients with ulcerative colitis.
AB  - BACKGROUND AND AIM: The gut microbiota is suggested to play an important role in
      the pathogenesis of ulcerative colitis (UC). However, interindividual and spatial
      variations hamper the identification of UC-related changes. We thus investigated
      paired mucosa-associated microbiota obtained from both inflamed and non-inflamed
      sites of UC patients and corresponding sites of non-inflammatory bowel disease
      (IBD) controls. METHODS: Mucosal biopsies of both inflamed and non-inflamed sites
      were obtained from 14 patients with active UC of the left-sided or proctitis
      type. Paired mucosal biopsies of the corresponding sites were obtained from 14
      non-IBD controls. The microbial community structure was investigated using 16S
      ribosomal RNA gene sequences, followed by data analysis using qiime and LEfSe
      softwares. RESULTS: Microbial alpha diversity in both inflamed and non-inflamed
      sites was significantly lower in UC patients compared with non-IBD controls.
      There were more microbes of the genus Cloacibacterium and the Tissierellaceae
      family, and there were less microbes of the genus Neisseria at the inflamed site
      when compared with the non-inflamed site in UC patients. Decreased abundance of
      the genera Prevotella, Eubacterium, Neisseria, Leptotrichia, Bilophila,
      Desulfovibrio, and Butyricimonas was evident at the inflamed site of UC patients
      compared with the corresponding site of non-IBD controls. Among these taxa, the
      genera Prevotella and Butyricimonas were also less abundant at the non-inflamed
      site of UC patients compared with the corresponding site in non-IBD controls.
      CONCLUSIONS: Mucosal microbial dysbiosis occurs at both inflamed and non-inflamed
      sites in UC patients. The taxa showing altered abundance in UC patients might
      mediate colonic inflammation.

PMID- 29462846
TI  - Authenticity, acceptability, and feasibility of a hybrid gynecology station for
      the Papanicolaou test as part of a clinical skills examination in Korea.
AB  - PURPOSE: The objective of this study was to evaluate the authenticity,
      acceptability, and feasibility of a hybrid station that combined a standardized
      patient encounter and a simulated Papanicolaou test. METHODS: We introduced a
      hybrid station in the routine clinical skills examination (CSE) for 335 third
      year medical students at 4 universities in Korea from December 1 to December 3,
      2014. After the tests, we conducted an anonymous survey on the authenticity,
      acceptability, and feasibility of the hybrid station. RESULTS: A total of 334
      medical students and 17 professors completed the survey. A majority of the
      students (71.6%) and professors (82.4%) agreed that the hybrid station was more
      authentic than the standard CSE. Over 60 percent of the students and professors
      responded that the station was acceptable for assessing the students' competence.
      Most of the students (75.2%) and professors (82.4%) assessed the required tasks
      as being feasible after reading the instructions. CONCLUSION: Our results showed
      that the hybrid CSE station was a highly authentic, acceptable, and feasible way
      to assess medical students' performance.

PMID- 29462847
TI  - Use of the ultrasound-based total malignancy score in the management of thyroid
      nodules.
AB  - PURPOSE: The purpose of this study was to validate the role of the total
      malignancy score (TMS) in identifying thyroid nodules suspicious for malignancy
      through the sum of their ultrasound features. METHODS: The local ethical
      committee approved this prospective observational study. We examined 231 nodules
      in 231 consecutive patients (164 females and 67 males; age range, 20 to 87 years;
      median age, 59 years; interquartile range, 48 to 70 years) who underwent
      ultrasound followed by fine-needle aspiration cytology (FNAC). The nodules were
      further classified using the TMS, which considers ultrasound features (number,
      echogenicity, structure, halo, margins, Doppler signal, calcifications, and
      growth), and the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC),
      which considers cytological features. Patients with non-negative nodules (TBSRTC
      categories III to VI) underwent histological analysis, repeated FNAC, or 2 years
      of regular ultrasound follow-up. The associations between the final diagnosis,
      each of the ultrasound features, and the TMS were estimated using the chi-square
      test, the Mann-Whitney U test, and multivariate logistic regression. A receiver
      operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy
      of the TMS. RESULTS: On ultrasound, 47% of the nodules (108 of 231) had a TMS >3,
      18% (42 of 231) had a TMS of 3, and 35% (81 of 231) had a TMS >3. The FNAC
      results of 85% of the nodules (196 of 231) were benign, while 15% (35 of 231) had
      non-negative results. Hypoechogenicity, solid structure, the presence of
      microcalcifications, and the number of nodules were independent predictors of the
      final diagnosis, and the diagnostic accuracy of the TMS was good (area under the
      ROC curve, 0.82). CONCLUSION: The TMS system is simple to use, reliable, easily
      reproducible, and closely reflects malignancy risk. Based on our results, FNAC
      could be limited to nodules with a TMS >=3 without missing any cases of
      carcinoma.

PMID- 29462848
TI  - Anti-Diabetic Effect of Cotreatment with Quercetin and Resveratrol in
      Streptozotocin-Induced Diabetic Rats.
AB  - Quercetin and resveratrol are known to have beneficial effects on the diabetes
      and diabetic complication, however, the effects of combined treatment of these
      compounds on diabetes are not fully revealed. Therefore, the present study was
      designed to investigate the combined antidiabetic action of quercetin (QE) and
      resveratrol (RS) in streptozotocin (STZ)-induced diabetic rats. To test the
      effects of co-treated with these compounds on diabetes, serum glucose, insulin,
      lipid profiles, oxidative stress biomarkers, and ions were determined.
      Additionally, the activities of hepatic glucose metabolic enzymes and
      histological analyses of pancreatic tissues were evaluated. 50 male Sprague
      Dawley rats were divided into five groups; normal control, 50 mg/kg STZ-induced
      diabetic, and three (30 mg/kg QE, 10 mg/kg RS, and combined) compound-treated
      diabetic groups. The elevated serum blood glucose levels, insulin levels, and
      dyslipidemia in diabetic rats were significantly improved by QE, RS, and combined
      treatments. Oxidative stress and tissue injury biomarkers were dramatically
      inhibited by these compounds. They also shown to improve the hematological
      parameters which were shown to the hyperlactatemia and ketoacidosis as main
      causes of diabetic complications. The compounds treatment maintained the
      activities of hepatic glucose metabolic enzymes and structure of pancreatic beta
      cells from the diabetes, and it is noteworthy that cotreatment with QE and RS
      showed the most preventive effect on the diabetic rats. Therefore, our study
      suggests that cotreatment with QE and RS has beneficial effects against diabetes.
      We further suggest that cotreatment with QE and RS has the potential for use as
      an alternative therapeutic strategy for diabetes.

PMID- 29462849
TI  - Synthetic 3',4'-Dihydroxyflavone Exerts Anti-Neuroinflammatory Effects in BV2
      Microglia and a Mouse Model.
AB  - Neuroinflammation is an immune response within the central nervous system against
      various proinflammatory stimuli. Abnormal activation of this response contributes
      to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and
      Huntington disease. Therefore, pharmacologic modulation of abnormal
      neuroinflammation is thought to be a promising approach to amelioration of
      neurodegenerative diseases. In this study, we evaluated the synthetic flavone
      derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory
      activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells,
      3',4'-dihydroxyflavone successfully inhibited production of chemokines such as
      nitric oxide and prostaglandin E2 and proinflammatory cytokines such as tumor
      necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It
      also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and
      nuclear factor (NF)-kappaB activation. This indicates that the anti-inflammatory
      activities of 3',4'-dihydroxyflavone might be related to suppression of the
      proinflammatory MAPK and NF-kappaB signaling pathways. Similar anti
      neuroinflammatory activities of the compound were observed in the mouse model.
      These findings suggest that 3',4'-dihydroxyflavone is a potential drug candidate
      for the treatment of microglia-related neuroinflammatory diseases.

PMID- 29462850
TI  - Effect of Atomic Charges on Octanol-Water Partition Coefficient Using Alchemical
      Free Energy Calculation.
AB  - The octanol-water partition coefficient (logPow) is an important index for
      measuring solubility, membrane permeability, and bioavailability in the drug
      discovery field. In this paper, the logPow values of 58 compounds were predicted
      by alchemical free energy calculation using molecular dynamics simulation. In
      free energy calculations, the atomic charges of the compounds are always fixed.
      However, they must be recalculated for each solvent. Therefore, three different
      sets of atomic charges were tested using quantum chemical calculations, taking
      into account vacuum, octanol, and water environments. The calculated atomic
      charges in the different environments do not necessarily influence the
      correlation between calculated and experimentally measured ?Gwater values. The
      largest correlation coefficient values of the solvation free energy in water and
      octanol were 0.93 and 0.90, respectively. On the other hand, the correlation
      coefficient of logPow values calculated from free energies, the largest of which
      was 0.92, was sensitive to the combination of the solvation free energies
      calculated from the calculated atomic charges. These results reveal that the
      solvent assumed in the atomic charge calculation is an important factor
      determining the accuracy of predicted logPow values.

PMID- 29462851
TI  - Alleviating Pancreatic Cancer-Associated Pain Using Endoscopic Ultrasound-Guided
      Neurolysis.
AB  - The most common symptom in patients with advanced pancreatic cancer is abdominal
      pain. This has traditionally been treated with nonsteroidal anti-inflammatory
      drugs and opioid analgesics. However, these treatments result in inadequate pain
      control or drug-related adverse effects in some patients. An alternative pain
      relief modality is celiac plexus neurolysis, in which the celiac plexus is
      chemically ablated. This procedure was performed percutaneously or
      intraoperatively until 1996, when endoscopic ultrasound (EUS)-guided celiac
      plexus neurolysis was first described. In this transgastric anterior approach, a
      neurolytic agent is injected around the celiac trunk under EUS guidance. The
      procedure gained popularity as a minimally invasive approach and is currently
      widely used to treat pancreatic cancer-associated pain. We focus on two
      relatively new techniques of EUS-guided neurolysis: EUS-guided celiac ganglia
      neurolysis and EUS-guided broad plexus neurolysis, which have been developed to
      improve efficacy. Although the techniques are safe and effective in general, some
      serious adverse events including ischemic and infectious complications have been
      reported as the procedure has gained widespread popularity. We summarize reported
      clinical outcomes of EUS-guided neurolysis in pancreatic cancer (from the PubMed
      and Embase databases) with a goal of providing information useful in developing
      strategies for pancreatic cancer-associated pain alleviation.

PMID- 29462852
TI  - Comparison of Structural and Functional Properties of Starches from the Rhizome
      and Bulbil of Chinese Yam.
AB  - Chinese yam is an important edible starch plant and widely cultivated in China.
      Its rhizome and bulbil are starch storage tissues below and above ground,
      respectively. In this paper, starches were isolated from the rhizome and bulbil
      of Chinese yam, and their structural and functional properties were compared.
      Both starches had an oval shape with an eccentric hilum and a CA-type crystalline
      structure. Their short-range ordered structure and lamellar structure had no
      significant difference. However, the rhizome starch had a significantly bigger
      granule size and lower amylose content than the bulbil starch. The swelling power
      and water solubility were significantly lower in the rhizome starch than in the
      bulbil starch. The onset and peak gelatinization temperatures were significantly
      higher in the rhizome starch than in the bulbil starch. The rhizome starch had a
      significantly higher breakdown viscosity and a lower setback viscosity than the
      bulbil starch. The thermal stability was lower in the rhizome starch than in the
      bulbil starch. The rhizome starch had a significantly lower resistance to
      hydrolysis and in vitro digestion than the bulbil starch. The above results
      provide important information for the utilization of rhizome and bulbil starches
      of Chinese yam.

PMID- 29462854
TI  - Chemical Composition of Pyroligneous Acid Obtained from Eucalyptus GG100 Clone.
AB  - The present study aimed to characterize the chemical composition of pyroligneous
      acid (PA) obtained from slow pyrolysis of the clone GG100 of Eucalyptus urophylla
      * Eucalyptus grandis. The efficiency of extraction of organic compounds by using
      different solvents-dichloromethane (DCM), diethyl ether (DE) and ethyl acetate
      (EA)-was evaluated. Wood discs were collected and carbonized at a heating rate of
      1.25  degrees C/min until 450  degrees C. Pyrolysis gases were trapped and
      condensed, yielding a crude liquid product (CLP), which was refined to obtain
      pure PA. Then liquid-liquid extraction was carried out. Each extracted fraction
      was analyzed by GC-MS and the chemical compounds were identified. Experimental
      results showed that a larger number of chemical compounds could be extracted by
      using DCM and EA in comparison to diethyl ether DE. A total number of 93
      compounds were identified, with phenolic compounds being the major group,
      followed by aldehydes and ketones, furans, pyrans and esters. Higher contents of
      guaiacol, phenol, cresols and furfural seem to explain the antibacterial and
      antifungal activity shown by PA, as reported previously in the literature.
      Experimental data indicated that the organic phase extracted from GG100 PA
      consists of a mixture of compounds similar to liquid smokes regularly used in the
      food industry.

PMID- 29462855
TI  - Enhanced Automated Guidance System for Horizontal Auger Boring Based on Image
      Processing.
AB  - Horizontal auger boring (HAB) is a widely used trenchless technology for the high
      accuracy installation of gravity or pressure pipelines on line and grade.
      Differing from other pipeline installations, HAB requires a more precise and
      automated guidance system for use in a practical project. This paper proposes an
      economic and enhanced automated optical guidance system, based on optimization
      research of light-emitting diode (LED) light target and five automated image
      processing bore-path deviation algorithms. An LED light target was optimized for
      many qualities, including light color, filter plate color, luminous intensity,
      and LED layout. The image preprocessing algorithm, direction location algorithm,
      angle measurement algorithm, deflection detection algorithm, and auto-focus
      algorithm, compiled in MATLAB, are used to automate image processing for
      deflection computing and judging. After multiple indoor experiments, this
      guidance system is applied in a project of hot water pipeline installation, with
      accuracy controlled within 2 mm in 48-m distance, providing accurate line and
      grade controls and verifying the feasibility and reliability of the guidance
      system.

PMID- 29462853
TI  - Organ-Specific Metabolic Shifts of Flavonoids in Scutellaria baicalensis at
      Different Growth and Development Stages.
AB  - Scutellaria baicalensis Georgi is a traditional Chinese herbal medicine mainly
      containing flavonoids that contribute to its bioactivities. In this study, the
      distributions and dynamic changes of flavonoid levels in various organs of S.
      baicalensis at different development stages were investigated by UHPLC-QTOF-MS/MS
      and HPLC-DAD methods. The results indicated that the metabolic profiles of S.
      baicalensis changed with growth and development. During the initial germination
      stage, the seeds mainly contained flavonols. With growth, the main kinds of
      flavonoids in S. baicalensis changed from flavonols to flavanones and flavones.
      The results also revealed that the accumulation of flavonoids in S. baicalensis
      is organ-specific. The flavones without 4'-OH groups mainly accumulate in the
      root and the flavanones mainly accumulate in aerial organs. Dynamic accumulation
      analysis showed that the main flavonoids in the root of S. baicalensis
      accumulated rapidly before the full-bloom stage, then changed to a small extent.
      The results suggested the proper harvest time for the aerial parts was at the
      initial stage of reproductive growth and the flower buds should be collected
      before flowering. This study deepening the knowledge of S. baicalensis should
      provide valuable information for guiding the scientific cultivation of this plant
      and the development and utilization of S. baicalensis.

PMID- 29462856
TI  - Morphological Pathways of Mitochondrial Division.
AB  - Mitochondrial fission is essential for distributing cellular energy throughout
      cells and for isolating damaged regions of the organelle that are targeted for
      degradation. Excessive fission is associated with the progression of cell death
      as well. Therefore, this multistep process is tightly regulated and several
      physiologic cues directly impact mitochondrial division. The double membrane
      structure of mitochondria complicates this process, and protein factors that
      drive membrane scission need to coordinate the separation of both the outer and
      inner mitochondrial membranes. In this review, we discuss studies that
      characterize distinct morphological changes associated with mitochondrial
      division. Specifically, coordinated partitioning and pinching of mitochondria
      have been identified as alternative mechanisms associated with fission.
      Additionally, we highlight the major protein constituents that drive
      mitochondrial fission and the role of connections with the endoplasmic reticulum
      in establishing sites of membrane division. Collectively, we review decades of
      research that worked to define the molecular framework of mitochondrial fission.
      Ongoing studies will continue to sort through the complex network of interactions
      that drive this critical event.

PMID- 29462857
TI  - Analysis Method for Laterally Loaded Pile Groups Using an Advanced Modeling of
      Reinforced Concrete Sections.
AB  - A Boundary Element Method (BEM) approach was developed for the analysis of pile
      groups. The proposed method includes: the non-linear behavior of the soil by a
      hyperbolic modulus reduction curve; the non-linear response of reinforced
      concrete pile sections, also taking into account the influence of tension
      stiffening; the influence of suction by increasing the stiffness of shallow
      portions of soil and modeled using the Modified Kovacs model; pile group
      shadowing effect, modeled using an approach similar to that proposed in the
      Strain Wedge Model for pile groups analyses. The proposed BEM method saves
      computational effort compared to more sophisticated codes such as VERSAT-P3D,
      PLAXIS 3D and FLAC-3D, and provides reliable results using input data from a
      standard site investigation. The reliability of this method was verified by
      comparing results from data from full scale and centrifuge tests on single piles
      and pile groups. A comparison is presented between measured and computed data on
      a laterally loaded fixed-head pile group composed by reinforced concrete bored
      piles. The results of the proposed method are shown to be in good agreement with
      those obtained in situ.

PMID- 29462858
TI  - Highly Efficient Intracellular Protein Delivery by Cationic Polyethyleneimine
      Modified Gelatin Nanoparticles.
AB  - Intracellular protein delivery may provide a safe and non-genome integrated
      strategy for targeting abnormal or specific cells for applications in cell
      reprogramming therapy. Thus, highly efficient intracellular functional protein
      delivery would be beneficial for protein drug discovery. In this study, we
      generated a cationic polyethyleneimine (PEI)-modified gelatin nanoparticle and
      evaluated its intracellular protein delivery ability in vitro and in vivo. The
      experimental results showed that the PEI-modified gelatin nanoparticle had a zeta
      potential of approximately +60 mV and the particle size was approximately 135 nm.
      The particle was stable at different biological pH values and temperatures and
      high protein loading efficiency was observed. The fluorescent image results
      revealed that large numbers of particles were taken up into the mammalian cells
      and escaped from the endosomes into the cytoplasm. In a mouse C26 cell-xenograft
      cancer model, particles accumulated in cancer cells. In conclusion, the PEI
      modified gelatin particle may provide a biodegradable and highly efficient
      protein delivery system for use in regenerative medicine and cancer therapy.

PMID- 29462859
TI  - Physical Health Care for People with Severe Mental Illness: the Attitudes,
      Practices, and Training Needs of Nurses in Three Asian Countries.
AB  - People with severe mental illness (SMI) have considerable unmet physical health
      needs and an increased risk of early mortality. This cross-sectional survey
      utilized the Physical Health Attitude Scale (PHASe) to examine the attitudes,
      practices, and training needs of nurses towards physical health care of people
      with SMI in three Asian countries (Hong Kong, Japan, Qatar). Cross-country
      differences were explored and linear regression was used to investigate if
      nurses' attitudes and confidence were associated with their level of involvement
      in physical health care. A total of 481 questionnaires were returned. Hong Kong
      nurses were less involved in physical health care than those from Japan and
      Qatar. Nurses' attitudes and confidence were significant predictors of their
      participation in managing physical health. Compared with western countries, more
      nurses in this study felt that mental illness was a barrier to improving physical
      health. Three-quarters reported that they needed additional training in promoting
      cardiometabolic health. The perceived need for additional training in physical
      health care was held by Mental Health Nurses (MHN) irrespective of their type of
      nursing registration and nationality. Nurse educators and service providers
      should reconsider the physical health care training requirements of nurses
      working in mental health settings in order to improve the physical health of
      people with SMI.

PMID- 29462860
TI  - Work-Family Conflict, Perceived Organizational Support and Professional
      Commitment: A Mediation Mechanism for Chinese Project Professionals.
AB  - Projects are characterized by long working hours, complex tasks and being a kind
      of temporary organization. As such, work-family conflict is particularly
      prominent for project employees. This research examined whether and how work
      family conflict affects professional commitment among Chinese project
      professionals. Research hypotheses were developed to explore the relationship
      between work-family conflict, professional commitment to the project and the
      mediating effects of perceived organizational support. Data were collected from
      327 project managers or professionals working in construction enterprises in
      China; data were analyzed using structural equation modeling, applying the
      bootstrapping method. Results showed that there were three dimensions of work
      family conflict: time-based conflict, strain-based conflict and behavior-based
      conflict. There were two dimensions of perceived organizational support:
      emotional support and instrumental support. The study also tested the negative
      effect of work-family conflict on professional commitment and the positive effect
      of perceived organizational support on professional commitment. Specifically,
      time-based conflict and emotional support had positive effects on professional
      commitment. Perceived organizational support had a total mediating effect between
      work-family conflict and professional commitment. The strain-based conflict
      dimension of work-family conflict had negative impacts on professional commitment
      through perceived emotional support and instrumental support. Overall, our
      findings extend a better understanding of work-family conflict and professional
      commitment in the project setting and verify the importance of social support in
      balancing work and family and improving employee mobility.

PMID- 29462861
TI  - Evaluating the Impacts of Health, Social Network and Capital on Craft Efficiency
      and Productivity: A Case Study of Construction Workers in China.
AB  - The construction industry has been recognized, for many years, as among those
      having a high likelihood of accidents, injuries and occupational illnesses. Such
      risks of construction workers can lead to low productivity and social problems.
      As a result, construction workers' well-being should be highly addressed to
      improve construction workers' efficiency and productivity. Meanwhile, the social
      support from a social network and capital (SNC) of construction workers has been
      considered as an effective approach to promote construction workers' physical and
      mental health (P&M health), as well as their work efficiency and productivity.
      Based on a comprehensive literature review, a conceptual model, which aims to
      improve construction workers' efficiency and productivity from the perspective of
      health and SNC, was proposed. A questionnaire survey was conducted to investigate
      the construction workers' health, SNC and work efficiency and productivity in
      Nanjing, China. A structural equation model (SEM) was employed to test the three
      hypothetical relationships among construction workers' P&M health, SNC and work
      efficiency and productivity. The results indicated that the direct impacts from
      construction workers' P&M health on work efficiency and productivity were more
      significant than that from the SNC. In addition, the construction workers' social
      capital and the network can indirectly influence the work efficiency and
      productivity by affecting the construction workers' P&M health. Therefore,
      strategies for enhancing construction workers' efficiency and productivity were
      proposed. Furthermore, many useable suggestions can be drawn from the research
      findings from the perspective of a government. The identified indicators and
      relationships would contribute to the construction work efficiency and
      productivity assessment and health management from the perspective of the
      construction workers.

PMID- 29462862
TI  - Evaluation of a Computer-Tailored Healthy Ageing Intervention to Promote Physical
      Activity among Single Older Adults with a Chronic Disease.
AB  - This study explores the effectiveness of the Active Plus65 intervention designed
      to stimulate physical activity among single older adults with a chronic physical
      impairment. A quasi-experimental pre-test post-test study was performed. The
      intervention group (n = 411; mean age = 76.75; SD = 7.75) was assessed at
      baseline, three months, and six months. Data of comparable older adults who
      completed the original Active Plus intervention served as reference group (n =
      87; mean age = 74.36; SD = 6.26). Multilevel regression analyses were applied:
      outcome measures were weekly minutes of moderate to vigorous physical activity
      (MVPA) and days per week with at least 30 minutes of MVPA. Although Active Plus65
      did not outperform the original intervention, in itself Active Plus65 effectuated
      a significant increase in the weekly minutes of MVPA (B = 208.26; p < 0.001;
      Effect Size (ES) = 0.45) and in the days per week with sufficient MVPA (B = 1.20;
      p < 0.001; ES = 0.61) after three months. After six months, it effectuated a
      significant increase in the days per week with sufficient MVPA (B = 0.67; p =
      0.001; ES = 0.34) but not for the weekly minutes of MVPA (p = 0.745). As Active
      Plus65 increased MVPA at three months with a higher ES than average interventions
      for this vulnerable target group, it potentially makes an interesting
      intervention. Further development should focus on long-term maintenance of
      effects.

PMID- 29462863
TI  - Effects of Vacation Rental Websites on the Concentration of Tourists-Potential
      Environmental Impacts. An Application to the Balearic Islands in Spain.
AB  - The concentration of tourists at certain times of the year can damage sensitive
      environments. The use of peer-to-peer vacation rental websites has increased
      greatly during the last decade. This system could either reduce seasonality in
      touristic destinations where the tourist activity takes place throughout the year
      at a lower price or on the contrary, it could increase the number of visitors at
      certain times of the year even more. This paper intends to analyze the effect
      that these platforms have on tourism seasonality in order to calculate if they
      help reduce or increase the pressure on the destinations. To do so, the Gini
      Index has been applied to one of the main touristic spots in Europe, the Balearic
      Islands in Spain. The conclusion is that this type of accommodation has
      aggravated the problem, generating a greater concentration of tourists and a
      higher pressure on the resources of the islands.

PMID- 29462864
TI  - Semi-Preparative Separation of 10 Caffeoylquinic Acid Derivatives Using High
      Speed Counter-Current Chromatogaphy Combined with Semi-Preparative HPLC from the
      Roots of Burdock (Arctium lappa L.).
AB  - Burdock roots are healthy dietary supplements and a kind of famous traditional
      Chinese medicine, which contains large amounts of caffeoylquinic acid
      derivatives. However, little research has been reported on the preparative
      separation of these compounds from burdock roots. In the present study, a
      combinative method of HSCCC and semi-preparative HPLC was developed for the semi
      preparative separation of caffeoylquinic acid derivatives from the burdock roots.
      The ethyl acetate extract of burdock roots was first fractionated by MCI
      macroporous resin chromatography and give three fractions (Fr. 1-3) from the
      elution of 40% methanol. Then, these three fractions (120 mg) were separately
      subjected to HSCCC for purification with the solvent system composed of petroleum
      ether-ethyl acetate-methanol-water at different volume ratios, and the mixtures
      were further purified by semi-preparative HPLC. As a result, a total of eight
      known caffeoylquinic acid derivatives including 3-O-caffeoylquinic acid (32.7 mg,
      95.7%), 1,5-O- dicaffeoylquinic acid (4.3 mg, 97.2%), 3-O-caffeoylquinic acid
      methyl ester (12.1 mg, 93.2%), 1,3-O-dicaffeoylquinic acid (42.9 mg, 91.1%), 1,5
      O-dicaffeoyl-3-O-(4-maloyl)-quinic acid (4.3 mg, 84.5%), 4,5-O-dicaffeoylquinic
      acid (5.3 mg, 95.5%), 1,5-O-dicaffeoyl-3-O-succinylquinic acid (8.7 mg, 93.4%),
      and 1,5-O-dicaffeoyl-4-O-succinylquinic acid (1.7 mg, 91.8%), and two new
      compounds were obtained. The new compounds were 1,4-O-dicaffeoyl-3-succinyl
      methyl ester quinic acid (14.6 mg, 96.1%) and 1,5-O-dicaffeoyl-3-O-succinyl
      methyl ester quinic acid (3.1 mg, 92.6%), respectively. The research indicated
      that the combination of HSCCC and semi-preparative HPLC is a highly efficient
      approach for preparative separation of the instability and bioactive
      caffeoylquinic acid derivatives from natural products.

PMID- 29462865
TI  - A Novel Method of Autonomous Inspection for Transmission Line based on Cable
      Inspection Robot LiDAR Data.
AB  - With the growth of the national economy, there is increasing demand for
      electricity, which forces transmission line corridors to become structurally
      complicated and extend to complex environments (e.g., mountains, forests). It is
      a great challenge to inspect transmission line in these regions. To address these
      difficulties, a novel method of autonomous inspection for transmission line is
      proposed based on cable inspection robot (CIR) LiDAR data, which mainly includes
      two steps: preliminary inspection and autonomous inspection. In preliminary
      inspection, the position and orientation system (POS) data is used for original
      point cloud dividing, ground point filtering, and structured partition. A
      hierarchical classification strategy is established to identify the classes and
      positions of the abnormal points. In autonomous inspection, CIR can autonomously
      reach the specified points through inspection planning. These inspection targets
      are imaged with PTZ (pan, tilt, zoom) cameras by coordinate transformation. The
      feasibility and effectiveness of the proposed method are verified by test site
      experiments and actual line experiments, respectively. The proposed method
      greatly reduces manpower and improves inspection accuracy, providing a
      theoretical basis for intelligent inspection of transmission lines in the future.

PMID- 29462867
TI  - On-Site Detection of Aflatoxin B1 in Grains by a Palm-Sized Surface Plasmon
      Resonance Sensor.
AB  - Aflatoxins (AFs) are highly toxic compounds that can cause both acute and chronic
      toxicity in humans. Aflatoxin B1 (AFB1) is considered the most toxic of AFs.
      Therefore, the rapid and on-site detection of AFB1 is critical for food safety
      management. Here, we report the on-site detection of AFB1 in grains by a portable
      surface plasmon resonance (SPR) sensor. For the detection of AFB1, the surface of
      an SPR Au chip was sequentially modified by cysteine-protein G, AFB1 antibody,
      and bovine serum albumin (BSA). Then, the sample solution and AFB1-BSA conjugate
      were flowed onto the Au chip in serial order. In the absence of AFB1, the SPR
      response greatly increased due to the binding of AFB1-BSA on the Au chip. In the
      presence of AFB1, the SPR response showed little change because the small AFB1
      molecule binds on the Au chip instead of the large AFB1-BSA molecule. By using
      this portable SPR-based competitive immunoassay, the sensor showed low limits of
      detection (2.51 ppb) and quantification (16.32 ppb). Furthermore, we successfully
      detected AFB1 in rice, peanut, and almond samples, which suggests that the
      proposed sensing method can potentially be applied to the on-site monitoring of
      mycotoxins in food.

PMID- 29462866
TI  - Traumatic Brain Injury, Sleep Disorders, and Psychiatric Disorders: An
      Underrecognized Relationship.
AB  - Traumatic brain injury (TBI) is commonplace among pediatric patients and has a
      complex, but intimate relationship with psychiatric disease and disordered sleep.
      Understanding the factors that influence the risk for the development of TBI in
      pediatrics is a critical component of beginning to address the consequences of
      TBI. Features that may increase risk for experiencing TBI sometimes overlap with
      factors that influence the development of post-concussive syndrome (PCS) and
      recovery course. Post-concussive syndrome includes physical, psychological,
      cognitive and sleep-wake dysfunction. The comorbid presence of sleep-wake
      dysfunction and psychiatric symptoms can lead to a more protracted recovery and
      deleterious outcomes. Therefore, a multidisciplinary evaluation following TBI is
      necessary. Treatment is generally symptom specific and mainly based on adult
      studies. Further research is necessary to enhance diagnostic and therapeutic
      approaches, as well as improve the understanding of contributing pathophysiology
      for the shared development of psychiatric disease and sleep-wake dysfunction
      following TBI.

PMID- 29462868
TI  - Inhibition of Cytochrome P450 Activities by Extracts of Hyptis verticillata
      Jacq.: Assessment for Potential HERB-Drug Interactions.
AB  - Understanding the potential for adverse drug reactions (ADRs), from herb-drug
      interactions, is a key aspect of medicinal plant safety, with particular
      relevance for public health in countries where medicinal plant use is highly
      prevalent. We undertook an in-depth assessment of extracts of Hyptis verticillata
      Jacq., via its impact on activities of key cytochrome P450 (CYP) enzymes (CYPs
      1A1, 1A2, 1B1, 3A4 and 2D6), its antioxidant properties (determined by DPPH
      assays) and chemical characterisation (using LC-MS). The dried plant aqueous
      extract demonstrated potent inhibition of the activities of CYPs 1A1 (7.6 ug/mL),
      1A2 (1.9 ug/mL), 1B1 (9.4 ug/mL) and 3A4 (6.8 ug/mL). Further analysis of other
      crude extracts demonstrated potent inhibition of CYP1A2 activity for a dried
      plant ethanol extract (1.5 ug/mL), fresh plant ethanol extract (3.9 ug/mL), and
      moderate activity for a fresh plant aqueous extract (27.8 ug/mL). All four
      extracts demonstrated strong antioxidant activity, compared to the positive
      control (ascorbic acid, 1.3 ug/mL), with the dried plant ethanol extract being
      the most potent (1.6 ug/mL). Analysis of the dried plant aqueous extract
      confirmed the identity of seven phytochemicals, five lignans and two triterpenes.
      Individual screening of these phytochemicals against the activity of CYP1A2
      identified yatein as a moderate inhibitor (71.9 MUM), likely to contribute to the
      plant extract's potent bioactivity. Further analysis on the impact of this plant
      on key drug metabolizing enzymes in vivo appears warranted for likely ADRs, as
      well as furthering development as a potential chemopreventive agent.

PMID- 29462869
TI  - Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney
      Disease.
AB  - Vascular endothelial growth factor A (VEGF-A) is a prominent pro-angiogenic and
      pro-permeability factor in the kidney. Alternative splicing of the terminal exon
      of VEGF-A through the use of an alternative 3' splice site gives rise to a
      functionally different family of isoforms, termed VEGF-Axxxb, known to have anti
      angiogenic and anti-permeability properties. Dysregulation of the VEGF-Axxx/VEGF
      Axxxb isoform balance has recently been reported in several kidney pathologies,
      including diabetic nephropathy (DN) and Denys-Drash syndrome. Using mouse models
      of kidney disease where the VEGF-A isoform balance is disrupted, several reports
      have shown that VEGF-A165b treatment/over-expression in the kidney is
      therapeutically beneficial. Furthermore, inhibition of certain splice factor
      kinases involved in the regulation of VEGF-A terminal exon splicing has provided
      some mechanistic insight into how VEGF-A splicing could be regulated in the
      kidney. This review highlights the importance of further investigation into the
      novel area of VEGF-A splicing in chronic kidney disease pathogenesis and how
      future studies may allow for the development of splicing-modifying therapeutic
      drugs.

PMID- 29462870
TI  - Responsive Polydiacetylene Vesicles for Biosensing Microorganisms.
AB  - Polydiacetylene (PDA) inserted in films or in vesicles has received increasing
      attention due to its property to undergo a blue-to-red colorimetric transition
      along with a change from non-fluorescent to fluorescent upon application of
      various stimuli. In this review paper, the principle for the detection of various
      microorganisms (bacteria, directly detected or detected through the emitted
      toxins or through their DNA, and viruses) and of antibacterial and antiviral
      peptides based on these responsive PDA vesicles are detailed. The analytical
      performances obtained, when vesicles are in suspension or immobilized, are given
      and compared to those of the responsive vesicles mainly based on the vesicle
      encapsulation method. Many future challenges are then discussed.

PMID- 29462871
TI  - Taming the Notch Transcriptional Regulator for Cancer Therapy.
AB  - Abstract Notch signaling is a highly conserved pathway in all metazoans, which is
      deeply involved in the regulation of cell fate and differentiation, proliferation
      and migration during development. Research in the last decades has shown that the
      various components of the Notch signaling cascade are either upregulated or
      activated in human cancers. Therefore, its downregulation stands as a promising
      and powerful strategy for cancer therapy. Here, we discuss the recent advances in
      the development of small molecule inhibitors, blocking antibodies and
      oligonucleotides that hinder Notch activity, and their outcome in clinical
      trials. Although Notch was initially identified as an oncogene, later studies
      showed that it can also act as a tumor suppressor in certain contexts. Further
      complexity is added by the existence of numerous Notch family members, which
      exert different activities and can be differentially targeted by inhibitors,
      potentially accounting for contradictory data on their therapeutic efficacy.
      Notably, recent evidence supports the rationale for combinatorial treatments
      including Notch inhibitors, which appear to be more effective than single agents
      in fighting cancer.

PMID- 29462873
TI  - The Lewis Pair Polymerization of Lactones Using Metal Halides and N-Heterocyclic
      Olefins: Theoretical Insights.
AB  - Lewis pair polymerization employing N-Heterocyclic olefins (NHOs) and simple
      metal halides as co-catalysts has emerged as a useful tool to polymerize diverse
      lactones. To elucidate some of the mechanistic aspects that remain unclear to
      date and to better understand the impact of the metal species, computational
      methods have been applied. Several key aspects have been considered: (1) the
      formation of NHO-metal halide adducts has been evaluated for eight different NHOs
      and three different Lewis acids, (2) the coordination of four lactones to MgCl2
      was studied and (3) the deprotonation of an initiator (butanol) was investigated
      in the presence and absence of metal halide for one specific Lewis pair. It was
      found that the propensity for adduct formation can be influenced, perhaps even
      designed, by varying both organic and metallic components. Apart from the NHO
      backbone, the substituents on the exocyclic, olefinic carbon have emerged as
      interesting tuning site. The tendency to form adducts is ZnCl2 > MgCl2 > LiCl. If
      lactones coordinate to MgCl2, the most likely binding mode is via the carbonyl
      oxygen. A chelating coordination cannot be ruled out and seems to gain importance
      upon increasing ring-size of the lactone. For a representative NHO, it is
      demonstrated that in a metal-free setting an initiating alcohol cannot be
      deprotonated, while in the presence of MgCl2 the same process is exothermic with
      a low barrier.

PMID- 29462872
TI  - Ten Years of Experience in Contraception Options for Teenagers in a Family
      Planning Center in Thrace and Review of the Literature.
AB  - Abstract: Introduction: The goal of our study was to investigate and evaluate the
      contraceptive behavior in teenagers from our family planning centre that services
      two different religious and socioeconomic populations living in the Thrace area.
      Methods: During the last 10 years 115 Christian Orthodox (group A) and 53 Muslim
      teenagers (group B) were enrolled in our retrospective study. Contraceptive
      practice attitudes were assessed by a questionnaire. Religion, demographics,
      socio-economic characteristics were key factors used to discuss contraception and
      avoid unplanned pregnancy in each group and to compare with the contraceptive
      method used. Results: The most used contraceptive method-about two times more
      frequently-among Christian Orthodox participants was the oral contraceptive pill
      (p = 0.015; OR = 1.81, 95% CI = 1.13-2.90), while in the other group the use of
      condoms and IUDs was seven and three times more frequent, respectively. Our
      family planning centre was the main source of information for contraception.
      Conclusions: During adolescence, the existence of a family planning centre and
      participation in family planning programs plays a crucial role to help the
      teenagers to improve their knowledge and choose an effective contraception
      method.

PMID- 29462874
TI  - Pd-Catalyzed, Highly Selective C(sp2)-Br Bond Coupling Reactions of o-(or m-, or
      p-) Chloromethyl Bromobenzene with Arylboronic Acids.
AB  - Highly selective C(sp2)-C(sp2) cross-coupling of dihalogenated hydrocarbons
      comprising C(sp2)-Br and C(sp3)-Cl bonds with arylboronic acids is reported. This
      highly selective coupling reaction of the C(sp2)-Br bond is successfully achieved
      using Pd(OAc)2 and PCy3.HBF4 as the palladium source and ligand, respectively. A
      series of chloromethyl-1,1'-biphenyl compounds are obtained in moderate-to
      excellent yields. Moreover, this protocol can be extended to the one-pot dual
      arylation of 1-bromo-4-(chloromethyl)benzene with two arylboronic acids, leading
      to diverse unsymmetrical 4-benzyl-1,1'-biphenyl derivatives.

PMID- 29462875
TI  - Extensive Degradation and Low Bioavailability of Orally Consumed Corn miRNAs in
      Mice.
AB  - The current study seeks to resolve the discrepancy in the literature regarding
      the cross-kingdom transfer of plant microRNAs (miRNAs) into mammals using an
      improved miRNA processing and detection method. Two studies utilizing C57BL/6
      mice were performed. In the first study, mice were fed an AIN-93M diet and
      gavaged with water, random deoxynucleotide triphosphates (dNTP) or isolated corn
      miRNAs for two weeks (n = 10 per group). In the second study, mice were fed an
      AIN-93M diet, or the diet supplemented with 3% fresh or autoclaved corn powder
      for two weeks (n = 10 per group). Corn miRNA levels were analyzed in blood and
      tissue samples by real-time PCR (RT-PCR) following periodate oxidation and beta
      elimination treatments to eliminate artifacts. After removing false positive
      detections, there were no differences in corn miRNA levels between control and
      treated groups in cecal, fecal, liver and blood samples. Using an in vitro
      digestion system, corn miRNAs in AIN-93M diet or in the extracts were found to be
      extensively degraded. Less than 1% was recovered in the gastrointestinal tract
      after oral and gastric phases. In conclusion, no evidence of increased levels of
      corn miRNAs in whole blood or tissues after supplementation of corn miRNAs in the
      diet was observed in a mouse model.

PMID- 29462876
TI  - Narcolepsy and Psychiatric Disorders: Comorbidities or Shared Pathophysiology?
AB  - Narcolepsy and psychiatric disorders have a significant but unrecognized
      relationship, which is an area of evolving interest, but unfortunately, the
      association is poorly understood. It is not uncommon for the two to occur co
      morbidly. However, narcolepsy is frequently misdiagnosed initially as a
      psychiatric condition, contributing to the protracted time to accurate diagnosis
      and treatment. Narcolepsy is a disabling neurodegenerative condition that carries
      a high risk for development of social and occupational dysfunction. Deterioration
      in function may lead to the secondary development of psychiatric symptoms.
      Inversely, the development of psychiatric symptoms can lead to the deterioration
      in function and quality of life. The overlap in pharmaceutical intervention may
      further enhance the difficulty to distinguish between diagnoses. Comprehensive
      care for patients with narcolepsy should include surveillance for psychiatric
      illness and appropriate treatment when necessary. Further research is necessary
      to better understand the underlying pathophysiology between psychiatric disease
      and narcolepsy.

PMID- 29462877
TI  - Characterization of the Symbiotic Nitrogen-Fixing Common Bean Low Phytic Acid
      (lpa1) Mutant Response to Water Stress.
AB  - The common bean (Phaseolus vulgaris L.) low phytic acid (lpa1) biofortified
      genotype produces seeds with improved nutritional characteristics and does not
      display negative pleiotropic effects. Here we demonstrated that lpa1 plants
      establish an efficient nitrogen-fixing symbiosis with Rhizobium etli CE3. The
      lpa1 nodules showed a higher expression of nodule-function related genes than the
      nodules of the parental wild type genotype (BAT 93). We analyzed the response to
      water stress of lpa1 vs. BAT 93 plants grown under fertilized or under symbiotic
      N2-fixation conditions. Water stress was induced by water withholding (up to 14%
      soil moisture) to fertilized or R. etli nodulated plants previously grown with
      normal irrigation. The fertilized lpa1 plants showed milder water stress symptoms
      during the water deployment period and after the rehydration recovery period when
      lpa1 plants showed less biomass reduction. The symbiotic water-stressed lpa1
      plants showed decreased nitrogenase activity that coincides with decreased
      sucrose synthase gene expression in nodules; lower turgor weight to dry weight
      (DW) ratio, which has been associated with higher drought resistance index;
      downregulation of carbon/nitrogen (C/N)-related and upregulation of stress
      related genes. Higher expression of stress-related genes was also observed in
      bacteroids of stressed lpa1 plants that also displayed very high expression of
      the symbiotic cbb3 oxidase (fixNd).

PMID- 29462878
TI  - Diagnostic Utility of High Sensitivity Troponins for Echocardiographic Markers of
      Structural Heart Disease.
AB  - The conventional use of high-sensitivity troponins (hs-troponins) is for
      diagnosing myocardial infarction however they also have a role in chronic disease
      management. This pilot study assessed the relationship of hs-troponins with
      echocardiographic markers of left ventricular hypertrophy (LVH) and structural
      heart disease (SHD). Patients undergoing computer gomography (CT) coronary
      angiogram for low-intermediate risk chest pain and healthy volunteers were
      recruited. Hs-troponins Singulex I, Abbott I and Roche T and N-terminal pro-brain
      natriuretic peptide (NT-proBNP) were evaluated in relation to SHD parameters
      including left ventricular hypertrophy (LVHEcho) and left atrial enlargement
      (LAEEcho) on echocardiography. 78 subjects who underwent echocardiography were
      included in this study. C-statistics (95% confidence interval) of the four
      biomarkers for predicting LVHEcho were 0.84 (0.72-0.92), 0.84 (0.73-0.92), 0.75
      (0.63-0.85) and 0.62 (0.49-0.74); for LAEEcho 0.74 (0.6-0.85), 0.78 (0.66-0.88),
      0.55 (0.42-0.67) and 0.68 (0.62-0.85); and composite SHD 0.79 (0.66-0.88), 0.87
      (0.75-0.94), 0.62 (0.49-0.73) and 0.74 (0.62-0.84) respectively. Optimal cut
      points for SHD were >1.2 ng/L, >1.6 ng/L, >8 ng/L and >18 pmol/L respectively.
      These results advocate the potential role of hs-troponins as screening tools for
      structural heart disease with theranostic implications.

PMID- 29462879
TI  - Chondrocytes Contribute to Alphaviral Disease Pathogenesis as a Source of Virus
      Replication and Soluble Factor Production.
AB  - Arthritogenic alphavirus infections often result in debilitating musculoskeletal
      disorders that affect the joints, muscle, and bone. In order to evaluate the
      infection profile of primary human skeletal muscle and chondrocyte cells to Ross
      River virus (RRV) in vitro, cells were infected at a multiplicity of infection
      (MOI) of 1 over a period of two days. Viral titers were determined by plaque
      assay and cytokine expression by Bio-Plex(r) assays using the supernatants
      harvested. Gene expression studies were conducted using total RNA isolated from
      cells. Firstly, we show that RRV RNA is detected in chondrocytes from infected
      mice in vivo. Both human primary skeletal muscle and chondrocyte cells are able
      to support productive RRV infection in vitro. We also report the production of
      soluble host factors including the upregulation of heparanase (HPSE) and
      inflammatory host factors such as interleukin-6 (IL-6), monocyte chemoattractant
      protein 1 (MCP-1), RANTES (regulated on activation, normal T cell expressed and
      secreted), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF
      alpha), which are also present during clinical disease in humans. Our study is
      the first to demonstrate that human chondrocyte cells are permissive to RRV
      infection, support the production of infectious virus, and produce soluble
      factors including HPSE, which may contribute to joint degradation and the
      pathogenesis of disease.

PMID- 29462880
TI  - Benzothiophenone Derivatives Targeting Mutant Forms of Estrogen Receptor-alpha in
      Hormone-Resistant Breast Cancers.
AB  - Estrogen receptor-alpha positive (ERalpha+) breast cancers represent 75% of all
      invasive breast cancer cases, while de novo or acquired resistance to ER-directed
      therapy is also on the rise. Numerous factors contribute to this phenomenon
      including the recently-reported ESR1 gene mutations such as Y537S, which
      amplifies co-activator interactions with ERalpha and promotes constitutive
      activation of ERalpha function. Herein, we propose that direct targeting of the
      activation function-2 (AF2) site on ERalpha represents a promising alternative
      therapeutic strategy to overcome mutation-driven resistance in breast cancer. A
      systematic computer-guided drug discovery approach was employed to develop a
      potent ERalpha inhibitor that was extensively evaluated by a series of
      experiments to confirm its AF2-specific activity. We demonstrate that the
      developed small-molecule inhibitor effectively prevents ERalpha-coactivator
      interactions and exhibits a strong anti-proliferative effect against tamoxifen
      resistant cells, as well as downregulates ERalpha-dependent genes and effectively
      diminishes the receptor binding to chromatin. Notably, the identified lead
      compound successfully inhibits known constitutively-active, resistance-associated
      mutant forms of ERalpha observed in clinical settings. Overall, this study
      reports the development of a novel class of ERalpha AF2 inhibitors, which have
      the potential to effectively inhibit ERalpha activity by a unique mechanism and
      to circumvent the issue of mutation-driven resistance in breast cancer.

PMID- 29462881
TI  - Healthiness of Food and Beverages for Sale at Two Public Hospitals in New South
      Wales, Australia.
AB  - (1) Background: Our aim was to conduct objective, baseline food environment
      audits of two major western Sydney public hospitals and compare them to recently
      revised state nutritional guidelines. (2) Methods: A cross-sectional assessment
      was conducted (June-July2017) across 14 fixed food outlets and 70 vending
      machines in two hospitals using an audit tool designed to assess the guideline's
      key food environment parameters of availability, placement, and promotion of
      'Everyday' (healthy) and 'Occasional' (less healthy) products. (3) Results:
      Availability: Overall, Everyday products made up 51% and 44% of all products
      available at the two hospitals. Only 1/14(7%) fixed outlets and 16/70(23%)
      vending machines met the guideline's availability benchmarks of >=75% Everyday
      food and beverages. Proportion of Everyday products differed among different
      types of food outlets (cafe, cafeteria, convenience stores). Placement: On
      average, food outlets did not meet recommendations of limiting Occasional
      products in prominent positions, with checkout areas and countertops displaying
      over 60% Occasional items. Promotion: Over two-thirds of meal deals at both
      hospitals included Occasional products. (4) Conclusion: Baseline audit results
      show that substantial improvements in availability, placement, and promotion can
      be made at these public hospitals to meet the nutrition guidelines. Audits of
      other NSW hospitals using the developed tool are needed to investigate
      similarities and differences in food environment between sites. These findings
      highlight the need for ongoing tracking to inform whether the revised guidelines
      are leading to improved food environments in health facilities.

PMID- 29462884
TI  - An Efficient Framework Model for Optimizing Routing Performance in VANETs.
AB  - Routing in Vehicular Ad hoc Networks (VANET) is a bit complicated because of the
      nature of the high dynamic mobility. The efficiency of routing protocol is
      influenced by a number of factors such as network density, bandwidth constraints,
      traffic load, and mobility patterns resulting in frequency changes in network
      topology. Therefore, Quality of Service (QoS) is strongly needed to enhance the
      capability of the routing protocol and improve the overall network performance.
      In this paper, we introduce a statistical framework model to address the problem
      of optimizing routing configuration parameters in Vehicle-to-Vehicle (V2V)
      communication. Our framework solution is based on the utilization of the network
      resources to further reflect the current state of the network and to balance the
      trade-off between frequent changes in network topology and the QoS requirements.
      It consists of three stages: simulation network stage used to execute different
      urban scenarios, the function stage used as a competitive approach to aggregate
      the weighted cost of the factors in a single value, and optimization stage used
      to evaluate the communication cost and to obtain the optimal configuration based
      on the competitive cost. The simulation results show significant performance
      improvement in terms of the Packet Delivery Ratio (PDR), Normalized Routing Load
      (NRL), Packet loss (PL), and End-to-End Delay (E2ED).

PMID- 29462882
TI  - Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling.
AB  - Glycosylation is a very frequent and functionally important post-translational
      protein modification that undergoes profound changes in cancer. Growth and death
      factor receptors and plasma membrane glycoproteins, which upon activation by
      extracellular ligands trigger a signal transduction cascade, are targets of
      several molecular anti-cancer drugs. In this review, we provide a thorough
      picture of the mechanisms bywhich glycosylation affects the activity of growth
      and death factor receptors in normal and pathological conditions. Glycosylation
      affects receptor activity through three non-mutually exclusive basic mechanisms:
      (1) by directly regulating intracellular transport, ligand binding,
      oligomerization and signaling of receptors; (2) through the binding of receptor
      carbohydrate structures to galectins, forming a lattice thatregulates receptor
      turnover on the plasma membrane; and (3) by receptor interaction with
      gangliosides inside membrane microdomains. Some carbohydrate chains, for example
      core fucose and beta1,6-branching, exert a stimulatory effect on all receptors,
      while other structures exert opposite effects on different receptors or in
      different cellular contexts. In light of the crucial role played by glycosylation
      in the regulation of receptor activity, the development of next-generation drugs
      targeting glyco-epitopes of growth factor receptors should be considered a
      therapeutically interesting goal.

PMID- 29462883
TI  - Using Polarized Spectroscopy to Investigate Order in Thin-Films of Ionic Self
      Assembled Materials Based on Azo-Dyes.
AB  - Three series of ionic self-assembled materials based on anionic azo-dyes and
      cationic benzalkonium surfactants were synthesized and thin films were prepared
      by spin-casting. These thin films appear isotropic when investigated with
      polarized optical microscopy, although they are highly anisotropic. Here, three
      series of homologous materials were studied to rationalize this observation.
      Investigating thin films of ordered molecular materials relies to a large extent
      on advanced experimental methods and large research infrastructure. A statement
      that in particular is true for thin films with nanoscopic order, where X-ray
      reflectometry, X-ray and neutron scattering, electron microscopy and atom force
      microscopy (AFM) has to be used to elucidate film morphology and the underlying
      molecular structure. Here, the thin films were investigated using AFM, optical
      microscopy and polarized absorption spectroscopy. It was shown that by using
      numerical method for treating the polarized absorption spectroscopy data, the
      molecular structure can be elucidated. Further, it was shown that polarized
      optical spectroscopy is a general tool that allows determination of the molecular
      order in thin films. Finally, it was found that full control of thermal history
      and rigorous control of the ionic self-assembly conditions are required to
      reproducibly make these materials of high nanoscopic order. Similarly, the
      conditions for spin-casting are shown to be determining for the overall thin film
      morphology, while molecular order is maintained.

PMID- 29462885
TI  - Hypoxia Activates Src and Promotes Endocytosis Which Decreases MMP-2 Activity and
      Aggravates Renal Interstitial Fibrosis.
AB  - The aggravation of renal interstitial fibrosis in the advanced-stage of chronic
      kidney disease is related to decreased matrix metalloproteinase-2 (MMP-2)
      activity, which is induced by hypoxia in the kidney; however, the specific
      mechanism remains unclear. We previously demonstrated that inhibition of Caveolin
      1, a key gene involved in endocytosis, increased MMP-2 activity in hypoxic HK-2
      cells. It has been reported that activated Src (phospho-Src Tyr416) is a key
      molecule in multiple fibrotic pathways. However, whether Src functions on the
      regulation of Caveolin-1 and MMP-2 activity in hypoxic HK-2 cells remains poorly
      understood. To explore the underlying mechanism, a rat model of renal
      interstitial fibrosis was established, then we observed obvious hypoxia in
      fibrotic kidney tissue and the protein levels of phospho-Src and Caveolin-1
      increased, while MMP-2 activity decreased. Next, we treated HK-2 cells with the
      phospho-Src inhibitor PP1. Compared with normal cells grown in hypoxia, in cells
      treated with PP1, the protein levels of phospho-Src and Caveolin-1 decreased, as
      did the protein levels of the MMP-2-activity-regulated molecules RECK (reversion
      inducing-cysteine-rich protein with kazal motifs) and TIMP-2 (tissue inhibitor of
      metalloproteinase-2), while the protein level of MT1-MMP (membrane type 1-matrix
      metalloproteinase) increased and MMP-2 activity was enhanced. Therefore, hypoxia
      promotes the phosphorylation of Src and phospho-Src can enhance the endocytosis
      of HK-2 cells, which leads to decreased MMP-2 activity and aggravates renal
      interstitial fibrosis.

PMID- 29462886
TI  - Lung Macrophage Phenotypes and Functional Responses: Role in the Pathogenesis of
      COPD.
AB  - Lung macrophages (LMs) are essential immune effector cells that are pivotal in
      both innate and adaptive immune responses to inhaled foreign matter. They either
      reside within the airways and lung tissues (from early life) or are derived from
      blood monocytes. Similar to macrophages in other organs and tissues, LMs have
      natural plasticity and can change phenotype and function depending largely on the
      microenvironment they reside in. Phenotype changes in lung tissue macrophages
      have been implicated in chronic inflammatory responses and disease progression of
      various chronic lung diseases, including Chronic Obstructive Pulmonary Disease
      (COPD). LMs have a wide variety of functional properties that include
      phagocytosis (inorganic particulate matter and organic particles, such as
      viruses/bacteria/fungi), the processing of phagocytosed material, and the
      production of signaling mediators. Functioning as janitors of the airways, they
      also play a key role in removing dead and dying cells, as well as cell debris
      (efferocytic functions). We herein review changes in LM phenotypes during chronic
      lung disease, focusing on COPD, as well as changes in their functional properties
      as a result of such shifts. Targeting molecular pathways involved in LM
      phenotypic shifts could potentially allow for future targeted therapeutic
      interventions in several diseases, such as COPD.

PMID- 29462887
TI  - Identifying Factors Related to Food Agency: Cooking Habits in the Spanish Adult
      Population-A Cross-Sectional Study.
AB  - This study focuses on understanding factors that influence food agency in the
      Spanish population, specifically with regard to cooking habits, knowledge, and
      determinants and their possible relationship with body weight. A cross-sectional
      telephone survey was conducted. Individuals were asked about their cooking
      responsibilities, how they learned to cook, factors that affect their food
      choices, and their preferred cooking techniques. Anthropometric data were also
      recorded. Participants were randomly selected, and we finally had 2026
      respondents aged >=18 years (60% women, 40% men). A total of 90.5% of
      participants stated that they had cooking skills. Women were mainly responsible
      for cooking tasks (p < 0.05) at all ages. A significantly higher proportion of
      people under 50 years self-reported that they were "able to cook" in comparison
      with groups over 50 years. Regardless of age, most participants learned to cook
      either by practice (43.3%) or from a family member (42.2%). Men tended to be more
      autodidactic, whereas women reported learning from family. No relation was found
      between weight status and the evaluated factors investigated. In conclusion,
      women bear the responsibility for the entire cooking process in families,
      indicating a gender gap in the involvement of men in cooking responsibilities and
      competence. More research is needed to assess the influence of cooking knowledge
      on obesity prevention.

PMID- 29462888
TI  - Microwave-Assisted Extraction for Microalgae: From Biofuels to Biorefinery.
AB  - The commercial reality of bioactive compounds and oil production from microalgal
      species is constrained by the high cost of production. Downstream processing,
      which includes harvesting and extraction, can account for 70-80% of the total
      cost of production. Consequently, from an economic perspective extraction
      technologies need to be improved. Microalgal cells are difficult to disrupt due
      to polymers within their cell wall such as algaenan and sporopollenin.
      Consequently, solvents and disruption devices are required to obtain products of
      interest from within the cells. Conventional techniques used for cell disruption
      and extraction are expensive and are often hindered by low efficiencies.
      Microwave-assisted extraction offers a possibility for extraction of biochemical
      components including lipids, pigments, carbohydrates, vitamins and proteins,
      individually and as part of a biorefinery. Microwave technology has advanced
      since its use in the 1970s. It can cut down working times and result in higher
      yields and purity of products. In this review, the ability and challenges in
      using microwave technology are discussed for the extraction of bioactive products
      individually and as part of a biorefinery approach.

PMID- 29462889
TI  - A Single Tri-Epitopic Antibody Virtually Recapitulates the Potency of a
      Combination of Three Monoclonal Antibodies in Neutralization of Botulinum
      Neurotoxin Serotype A.
AB  - The standard of treatment for botulism, equine antitoxin, is a foreign protein
      with associated safety issues and a short serum half-life which excludes its use
      as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to
      these limitations, a recombinant monoclonal antibody (mAb) product is preferable.
      It has been shown that combining three mAbs that bind non-overlapping epitopes
      leads to highly potent botulinum neurotoxin (BoNT) neutralization. Recently, a
      triple human antibody combination for BoNT/A has demonstrated potent toxin
      neutralization in mouse models with no serious adverse events when tested in a
      Phase I clinical trial. However, a triple antibody therapeutic poses unique
      development and manufacturing challenges. Thus, potentially to streamline
      development of BoNT antitoxins, we sought to achieve the potency of multiple mAb
      combinations in a single IgG-based molecule that has a long serum half-life. The
      design, production, and testing of a single tri-epitopic IgG1-based mAb (TeAb)
      containing the binding sites of each of the three parental BoNT/A mAbs yielded an
      antibody of nearly equal potency to the combination. The approach taken here
      could be applied to the design and creation of other multivalent antibodies that
      could be used for a variety of applications, including toxin elimination.

PMID- 29462890
TI  - Antiproliferative Activity of Glycosaminoglycan-Like Polysaccharides Derived from
      Marine Molluscs.
AB  - Despite the increasing availability of new classes of cancer treatment, such as
      immune- and targeted therapies, there remains a need for the development of new
      antiproliferative/cytotoxic drugs with improved pharmacological profiles that can
      also overcome drug resistant forms of cancer. In this study, we have identified,
      and characterised, a novel marine polysaccharide with the potential to be
      developed as an anticancer agent. Sulphated polysaccharides isolated from the
      common cockle (Cerastoderma edule) were shown to have antiproliferative activity
      on chronic myelogenous leukaemia and relapsed acute lymphoblastic leukaemia cell
      lines. Disaccharide and monosaccharide analysis of these marine polysaccharides
      confirmed the presence of glycosaminoglycan-like structures that were enriched in
      ion-exchange purified fractions containing antiproliferative activity. The
      antiproliferative activity of these glycosaminoglycan-like marine polysaccharides
      was shown to be susceptible to heparinase but not chondrotinase ABC digestion.
      This pattern of enzymatic and antiproliferative activity has not previously been
      seen, with either marine or mammalian glycosaminoglycans. As such, our findings
      suggest we have identified a new type of marine derived heparan sulphate/heparin
      like polysaccharide with potent anticancer properties.

PMID- 29462891
TI  - Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor
      Molecules.
AB  - pH is a tightly regulated physiological parameter that is often altered in
      diseased states like cancer. The development of biosensors that can be used to
      non-invasively image pH with hyperpolarized (HP) magnetic resonance spectroscopic
      imaging has therefore recently gained tremendous interest. However, most of the
      known HP-sensors have only individually and not comprehensively been analyzed for
      their biocompatibility, their pH sensitivity under physiological conditions, and
      the effects of chemical derivatization on their logarithmic acid dissociation
      constant (pKa). Proteinogenic amino acids are biocompatible, can be
      hyperpolarized and have at least two pH sensitive moieties. However, they do not
      exhibit a pH sensitivity in the physiologically relevant pH range. Here, we
      developed a systematic approach to tailor the pKa of molecules using
      modifications of carbon chain length and derivatization rendering these molecules
      interesting for pH biosensing. Notably, we identified several derivatives such as
      [1-13C]serine amide and [1-13C]-2,3-diaminopropionic acid as novel pH sensors.
      They bear several spin-1/2 nuclei (13C, 15N, 31P) with high sensitivity up to 4.8
      ppm/pH and we show that 13C spins can be hyperpolarized with dissolution dynamic
      polarization (DNP). Our findings elucidate the molecular mechanisms of chemical
      shift pH sensors that might help to design tailored probes for specific pH in
      vivo imaging applications.

PMID- 29462892
TI  - High Prevalence of Quorum-Sensing and Quorum-Quenching Activity among Cultivable
      Bacteria and Metagenomic Sequences in the Mediterranean Sea.
AB  - There is increasing evidence being accumulated regarding the importance of N-acyl
      homoserine lactones (AHL)-mediated quorum-sensing (QS) and quorum-quenching (QQ)
      processes in the marine environment, but in most cases, data has been obtained
      from specific microhabitats, and subsequently little is known regarding these
      activities in free-living marine bacteria. The QS and QQ activities among 605
      bacterial isolates obtained at 90 and 2000 m depths in the Mediterranean Sea were
      analyzed. Additionally, putative QS and QQ sequences were searched in metagenomic
      data obtained at different depths (15-2000 m) at the same sampling site. The
      number of AHL producers was higher in the 90 m sample (37.66%) than in the 2000 m
      sample (4.01%). However, the presence of QQ enzymatic activity was 1.63-fold
      higher in the 2000 m sample. The analysis of putative QQ enzymes in the
      metagenomes supports the relevance of QQ processes in the deepest samples, found
      in cultivable bacteria. Despite the unavoidable biases in the cultivation methods
      and biosensor assays and the possible promiscuous activity of the QQ enzymes
      retrieved in the metagenomic analysis, the results indicate that AHL-related QS
      and QQ processes could be common activity in the marine environment.

PMID- 29462893
TI  - Social Determinants of Perceived Discrimination among Black Youth: Intersection
      of Ethnicity and Gender.
AB  - Most of the existing sociological and epidemiological literature has focused on
      the protective effects of high socioeconomic status (SES) on population health
      through reducing exposure to risk factors and increasing human and material
      resources that can mitigate adversities. Recent studies, however, have documented
      poor mental health of high SES Blacks, particularly African American males and
      Caribbean Black females. The literature also shows a link between perceived
      discrimination and poor mental health. To better understand the extra costs of
      upward social mobility for minority populations, this study explored ethnic by
      gender variations in the associations between SES indicators and perceived
      discrimination in an ethnically diverse national sample of Black youth. This
      study included 810 African American and 360 Caribbean Black youth who were
      sampled in the National Survey of American Life-Adolescent supplement (NSAL-A).
      Three SES indicators (financial hardship, family income, and income to needs
      ratio) were the independent variables. The dependent variable was perceived
      (daily) discrimination. Age was the covariate. Ethnicity and gender were the
      focal moderators. Linear regressions were used for data analysis in the pooled
      sample and also based on the intersection of ethnicity and gender. Considerable
      gender by ethnicity variations were found in the patterns of the associations
      between SES indicators and perceived discrimination. Financial hardship was a
      risk factor for perceived discrimination in African American males only. High
      family income and income to needs ratio were associated with high (but not low)
      perceived discrimination in African American males and Caribbean Black females.
      SES indicators were not associated with perceived discrimination for African
      American females or Caribbean Black males. When it comes to Black youth, high SES
      is not always protective. Whether SES reduces or increases perceived
      discrimination among Black youth depends on the intersection of ethnicity by
      gender. Additional research is needed to understand why and how high SES
      increases exposure and vulnerability to discrimination for some groups of Black
      youth.

PMID- 29462894
TI  - Modeling the Role of Wnt Signaling in Human and Drosophila Stem Cells.
AB  - The discovery of induced pluripotent stem (iPS) cells, barely more than a decade
      ago, dramatically transformed the study of stem cells and introduced a completely
      new way to approach many human health concerns. Although advances have pushed the
      field forward, human application remains some years away, in part due to the need
      for an in-depth mechanistic understanding. The role of Wnts in stem cells
      predates the discovery of iPS cells with Wnts established as major pluripotency
      promoting factors. Most work to date has been done using mouse and tissue culture
      models and few attempts have been made in other model organisms, but the recent
      combination of clustered regularly interspaced short palindromic repeats (CRISPR)
      gene editing with iPS cell technology provides a perfect avenue for exploring iPS
      cells in model organisms. Drosophila is an ideal organism for such studies, but
      fly iPS cells have not yet been made. In this opinion article, we draw parallels
      between Wnt signaling in human and Drosophila stem cell systems, propose ways to
      obtain Drosophila iPS cells, and suggest ways to exploit the versatility of the
      Drosophila system for future stem cell studies.

PMID- 29462895
TI  - Design, Synthesis and DFT/DNP Modeling Study of New 2-Amino-5-arylazothiazole
      Derivatives as Potential Antibacterial Agents.
AB  - A new series of 2-amino-5-arylazothiazole derivatives has been designed and
      synthesized in 61-78% yields and screened as potential antibacterial drug
      candidates against the Gram negative bacterium Escherichia coli. The geometry of
      the title compounds were being studied using the Material Studio package and semi
      core pseudopods calculations (dspp) were performed with the double numerica basis
      sets plus polarization functional (DNP) to predict the properties of materials
      using the hybrid FT/B3LYP method. Modeling calculations, especially the (EH-EL)
      difference and the energetic parameters revealed that some of the title compounds
      may be promising tools for further research work and the activity is structure
      dependent.

PMID- 29462896
TI  - Dietary Fiber Treatment Corrects the Composition of Gut Microbiota, Promotes SCFA
      Production, and Suppresses Colon Carcinogenesis.
AB  - Epidemiological studies propose a protective role for dietary fiber in colon
      cancer (CRC). One possible mechanism of fiber is its fermentation property in the
      gut and ability to change microbiota composition and function. Here, we
      investigate the role of a dietary fiber mixture in polyposis and elucidate
      potential mechanisms using TS4Cre*cAPCl degrees x468 mice. Stool microbiota
      profiling was performed, while functional prediction was done using PICRUSt.
      Stool short-chain fatty acid (SCFA) metabolites were measured. Histone
      acetylation and expression of SCFA butyrate receptor were assessed. We found that
      SCFA-producing bacteria were lower in the polyposis mice, suggesting a decline in
      the fermentation product of dietary fibers with polyposis. Next, a high fiber
      diet was given to polyposis mice, which significantly increased SCFA-producing
      bacteria as well as SCFA levels. This was associated with an increase in SCFA
      butyrate receptor and a significant decrease in polyposis. In conclusion, we
      found polyposis to be associated with dysbiotic microbiota characterized by a
      decline in SCFA-producing bacteria, which was targetable by high fiber treatment,
      leading to an increase in SCFA levels and amelioration of polyposis. The
      prebiotic activity of fiber, promoting beneficial bacteria, could be the key
      mechanism for the protective effects of fiber on colon carcinogenesis. SCFA
      promoting fermentable fibers are a promising dietary intervention to prevent CRC.

PMID- 29462897
TI  - Molecular Cloning and Characterization of a Wild Eggplant Solanum aculeatissimum
      NBS-LRR Gene, Involved in Plant Resistance to Meloidogyne incognita.
AB  - Root-knot nematodes, Meloidogyne spp., cause considerable damage in eggplant
      production. Transferring of resistance genes from wild relatives would be
      valuable for the continued improvement of eggplant. Solanum aculeatissimum, a
      wild relative of eggplant possessing resistance to Meloidogyne incognita, is
      potentially useful for genetically enhancing eggplant. In the present study, we
      have isolated and characterized a nucleotide-binding site leucine-rich repeat
      (NBS-LRR) resistance gene, designated as SacMi. The full-length cDNA of the SacMi
      gene was obtained using the technique of rapid-amplification of cDNA ends (RACE).
      The open reading frame of the SacMi gene was 4014 bp and encoded a protein of
      1338 amino acids. Sequence analysis indicated that SacMi belong to the non-
      Toll/Interleukin-1 receptor (TIR)-NBS-LRR type disease-resistance genes.
      Interestingly, quantitative RT-PCR showed that SacMi is expressed at low levels
      in uninfected roots, but was up-regulated by infection with M. incognita. To
      investigate the role of SacMi in S. aculeatissimum resistance against M.
      incognica, the tobacco rattle virus (TRV)-mediated virus-induced gene silencing
      (VIGS) system was used. Silencing of SacMi enhanced susceptibility of S.
      aculeatissimum plants to M. incognita, suggesting the possible involvement of
      SacMi in resistance against M. incognita infection.

PMID- 29462898
TI  - Do Nonalcoholic Fatty Liver Disease and Fetuin-A Play Different Roles in
      Symptomatic Coronary Artery Disease and Peripheral Arterial Disease?
AB  - BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is strongly
      associated with both atherosclerotic cardiovascular disease (CVD) and Fetuin-A.
      However, the association of Fetuin-A with atherosclerosis is more controversial.
      We hypothesized that the pathogenic interplay of NAFLD, Fetuin-A and
      atherosclerosis varies based on arterial site. Accordingly, we aimed to assess
      NAFLD prevalence, Fetuin-A values and their relationship with symptomatic
      atherosclerosis occurring in different localizations: coronary artery disease
      (CAD) vs. peripheral arterial disease (PAD). METHODS: One hundred and forty-nine
      consecutive patients with symptomatic atherosclerotic CVD were recruited: 45 with
      CAD diagnosed by coronary angiography and 104 with PAD detected by doppler
      ultrasound and/or computed tomography angiography and/or angiography. NAFLD was
      diagnosed based on both ultrasonography and exclusion of competing etiologies.
      Serum Fetuin-A was measured with ELISA. RESULTS: NAFLD was detected in 54% of the
      overall group, with higher rates in PAD (59%) than CAD (42%) patients. Median
      Fetuin-A values were 256 (111-662) MUg/mL, higher in patients with CAD (378 (124
      662) MUg/mL) than those with PAD (236 (111-461) MUg/mL). The main findings were:
      (1) CAD patients had higher Fetuin-A values and less frequently NAFLD than PAD
      patients; (2) NAFLD was positively associated with Fetuin-A values; however, this
      association was limited to CAD patients only; (3) Fetuin-A values were positively
      associated with both CAD and NAFLD. CONCLUSION: The pathogenic interplay of
      NAFLD, Fetuin-A and atherosclerosis probably varies according to the arterial
      site.

PMID- 29462899
TI  - "I Wouldn't Be Friends with Someone If They Were Liking Too Much Rubbish": A
      Qualitative Study of Alcohol Brands, Youth Identity and Social Media.
AB  - The consumption of alcohol by young people remains a major public health concern
      at both the national and international level. Levels of drinking among 15
      yearolds in the United Kingdom (UK) remain significantly higher than the European
      average. This study explored how alcohol brands are used by young people to
      develop their desired identities and how these acts of consumption extend to
      young people's profiles on social media. It also deepens understanding of how
      alcohol brands are connected to young peoples' concerns about image and peer
      group dynamics. This involved qualitative focus groups with young people aged 14
      17 in Central Scotland. Certain alcohol brands were approved and viewed as
      socially acceptable by young people, while others were rejected. Children as
      young as 14 were selecting products to portray a drinking identity that was
      appropriately aligned to their gender and sexuality. Participants displayed a
      desire to associate themselves with the mature drinking culture personified by
      some brands, whilst simultaneously distancing themselves from immature drinking
      practices associated with others. Publicly associating with alcohol brands on
      social media carried with it potential risks to peer group acceptance.
      Understanding how young people perceive alcohol brands, the importance of social
      media in communicating that identity to their peers and the role that alcohol
      brands play in adolescent identity formation is an important first step to
      reforming alcohol marketing regulations.

PMID- 29462901
TI  - Nanogels for Pharmaceutical and Biomedical Applications and Their Fabrication
      Using 3D Printing Technologies.
AB  - Nanogels are hydrogels formed by connecting nanoscopic micelles dispersed in an
      aqueous medium, which give an opportunity for incorporating hydrophilic payloads
      to the exterior of the micellar networks and hydrophobic payloads in the core of
      the micelles. Biomedical and pharmaceutical applications of nanogels have been
      explored for tissue regeneration, wound healing, surgical device, implantation,
      and peroral, rectal, vaginal, ocular, and transdermal drug delivery. Although it
      is still in the early stages of development, due to the increasing demands of
      precise nanogel production to be utilized for personalized medicine, biomedical
      applications, and specialized drug delivery, 3D printing has been explored in the
      past few years and is believed to be one of the most precise, efficient,
      inexpensive, customizable, and convenient manufacturing techniques for nanogel
      production.

PMID- 29462902
TI  - Ring Laser Gyro G-Sensitive Misalignment Calibration in Linear Vibration
      Environments.
AB  - The ring laser gyro (RLG) dither axis will bend and exhibit errors due to the
      specific forces acting on the instrument, which are known as g-sensitive
      misalignments of the gyros. The g-sensitive misalignments of the RLG triad will
      cause severe attitude error in vibration or maneuver environments where large
      amplitude specific forces and angular rates coexist. However, g-sensitive
      misalignments are usually ignored when calibrating the strapdown inertial
      navigation system (SINS). This paper proposes a novel method to calibrate the g
      sensitive misalignments of an RLG triad in linear vibration environments. With
      the SINS is attached to a linear vibration bench through outer rubber dampers,
      rocking of the SINS can occur when the linear vibration is performed on the SINS.
      Therefore, linear vibration environments can be created to simulate the harsh
      environment during aircraft flight. By analyzing the mathematical model of g
      sensitive misalignments, the relationship between attitude errors and specific
      forces as well as angular rates is established, whereby a calibration scheme with
      approximately optimal observations is designed. Vibration experiments are
      conducted to calibrate g-sensitive misalignments of the RLG triad. Vibration
      tests also show that SINS velocity error decreases significantly after g
      sensitive misalignments compensation.

PMID- 29462900
TI  - Next Generation Immunotherapy for Pancreatic Cancer: DNA Vaccination is Seeking
      New Combo Partners.
AB  - Pancreatic Ductal Adenocarcinoma (PDA) is an almost incurable radio- and chemo
      resistant tumor, and its microenvironment is characterized by a strong
      desmoplastic reaction associated with a significant infiltration of T regulatory
      lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC). Investigating
      immunological targets has identified a number of metabolic and cytoskeletal
      related molecules, which are typically recognized by circulating antibodies.
      Among these molecules we have investigated alpha-enolase (ENO1), a glycolytic
      enzyme that also acts a plasminogen receptor. ENO1 is also recognized by T cells
      in PDA patients, so we developed a DNA vaccine that targets ENO1. This
      efficiently induces many immunological processes (antibody formation and
      complement-dependent cytotoxicity (CDC)-mediated tumor killing, infiltration of
      effector T cells, reduction of infiltration of myeloid and Treg suppressor
      cells), which significantly increase the survival of genetically engineered mice
      that spontaneously develop pancreatic cancer. Although promising, the ENO1 DNA
      vaccine does not completely eradicate the tumor, which, after an initial growth
      inhibition, returns to proliferate again, especially when Tregs and MDSC ensue in
      the tumor mass. This led us to develop possible strategies for combinatorial
      treatments aimed to broaden and sustain the antitumor immune response elicited by
      DNA vaccination. Based on the data we have obtained in recent years, this review
      will discuss the biological bases of possible combinatorial treatments
      (chemotherapy, PI3K inhibitors, tumor-associated macrophages, ENO1 inhibitors)
      that could be effective in amplifying the response induced by the immune
      vaccination in PDA.

PMID- 29462903
TI  - Calcium Imaging of GPCR Activation Using Arrays of Reverse Transfected HEK293
      Cells in a Microfluidic System.
AB  - Reverse-transfected cell arrays in microfluidic systems have great potential to
      perform large-scale parallel screening of G protein-coupled receptor (GPCR)
      activation. Here, we report the preparation of a novel platform using reverse
      transfection of HEK293 cells, imaging by stereo-fluorescence microscopy in a
      flowcell format, real-time monitoring of cytosolic calcium ion fluctuations using
      the fluorescent protein Cameleon and analysis of GPCR responses to sequential
      sample exposures. To determine the relationship between DNA concentration and
      gene expression, we analyzed cell arrays made with variable concentrations of
      plasmid DNA encoding fluorescent proteins and the Neurokinin 1 (NK1) receptor. We
      observed pronounced effects on gene expression of both the specific and total DNA
      concentration. Reverse transfected spots with NK1 plasmid DNA at 1% of total DNA
      still resulted in detectable NK1 activation when exposed to its ligand. By
      varying the GPCR DNA concentration in reverse transfection, the sensitivity and
      robustness of the receptor response for sequential sample exposures was
      optimized. An injection series is shown for an array containing the NK1 receptor,
      bitter receptor TAS2R8 and controls. Both receptors were exposed 14 times to
      alternating samples of two ligands. Specific responses remained reproducible.
      This platform introduces new opportunities for high throughput screening of GPCR
      libraries.

PMID- 29462904
TI  - Effect of Pyruvate Decarboxylase Knockout on Product Distribution Using Pichia
      pastoris (Komagataella phaffii) Engineered for Lactic Acid Production.
AB  - Lactic acid is the monomer unit of the bioplastic poly-lactic acid (PLA). One
      candidate organism for lactic acid production is Pichia pastoris, a yeast widely
      used for heterologous protein production. Nevertheless, this yeast has a poor
      fermentative capability that can be modulated by controlling oxygen levels. In a
      previous study, lactate dehydrogenase (LDH) activity was introduced into P.
      pastoris, enabling this yeast to produce lactic acid. The present study aimed to
      increase the flow of pyruvate towards the production of lactic acid in P.
      pastoris. To this end, a strain designated GLp was constructed by inserting the
      bovine lactic acid dehydrogenase gene (LDHb) concomitantly with the interruption
      of the gene encoding pyruvate decarboxylase (PDC). Aerobic fermentation, followed
      by micro-aerophilic culture two-phase fermentations, showed that the GLp strain
      achieved a lactic acid yield of 0.65 g/g. The distribution of fermentation
      products demonstrated that the acetate titer was reduced by 20% in the GLp strain
      with a concomitant increase in arabitol production: arabitol increased from 0.025
      g/g to 0.174 g/g when compared to the GS115 strain. Taken together, the results
      show a significant potential for P. pastoris in producing lactic acid. Moreover,
      for the first time, physiological data regarding co-product formation have
      indicated the redox balance limitations of this yeast.

PMID- 29462905
TI  - Diversity of Concerns in Recovery after a Nuclear Accident: A Perspective from
      Fukushima.
AB  - Since the 2011 Fukushima nuclear accident, tremendous resources have been devoted
      to recovery, and the Japanese Government is gradually lifting evacuation orders.
      However, public concerns remain prevalent, affecting some people's return to a
      normal life and threatening their well-being. This study reviews government
      reports, academic papers, newspaper articles and conference presentations with
      the aim of obtaining a better understanding of issues which relate to radiation
      concerns in the recovery process in the aftermath of the accident. It looks
      extensively at: (1) the current status of the post-accident operations and
      existing radiation issues in Fukushima, and (2) approaches taken to engage the
      public during recovery from five previous comparable nuclear and radiological
      events: Three Mile Island, Buenos Aires (RA-2 facility), Chernobyl, Goiania and
      Tokai-mura. The findings indicate that the limitations and emerging challenges of
      the current recovery operations cause concerns about radiation exposure in
      various aspects of day-to-day life. Past experiences suggest that long-term
      management that take a holistic and cohesive approach is critical for restoration
      of sustainable livelihoods and for social re-integration. Not only actual risks
      but also public perceptions of risks should be carefully assessed and addressed
      in the process of environmental remediation.

PMID- 29462906
TI  - The Epithelial-to-Mesenchymal Transition in Cancer.
AB  - The epithelial-to-mesenchymal transition (EMT) occurs during normal embryonic
      development, tissue regeneration, organ fibrosis, and wound healing.[...].

PMID- 29462907
TI  - Spectral Optical Readout of Rectangular-Miniature Hollow Glass Tubing for
      Refractive Index Sensing.
AB  - For answering the growing demand of innovative micro-fluidic devices able to
      measure the refractive index of samples in extremely low volumes, this paper
      presents an overview of the performances of a micro-opto-fluidic sensing platform
      that employs rectangular, miniature hollow glass tubings. The operating principle
      is described by showing the analytical model of the tubing, obtained as
      superposition of different optical cavities, and the optical readout method based
      on spectral reflectivity detection. We have analyzed, in particular, the
      theoretical and experimental optical features of rectangular tubings with
      asymmetrical geometry, thus with channel depth larger than the thickness of the
      glass walls, though all of them in the range of a few tens of micrometers. The
      origins of the complex line-shape of the spectral response in reflection, due to
      the different cavities formed by the tubing flat walls and channel, have been
      investigated using a Fourier transform analysis. The implemented instrumental
      configuration, based on standard telecom fiberoptic components and a
      semiconductor broadband optical source emitting in the near infrared wavelength
      region centered at 1.55 um, has allowed acquisition of reflectivity spectra for
      experimental verification of the expected theoretical behavior. We have achieved
      detection of refractive index variations related to the change of concentration
      of glucose-water solutions flowing through the tubing by monitoring the spectral
      shift of the optical resonances.

PMID- 29462908
TI  - Research on the Multiple Factors Influencing Human Identification Based on
      Pyroelectric Infrared Sensors.
AB  - Analysis of the multiple factors affecting human identification ability based on
      pyroelectric infrared technology is a complex problem. First, we examine various
      sensed pyroelectric waveforms of the human body thermal infrared signal and
      reveal a mechanism for affecting human identification. Then, we find that the
      mechanism is decided by the distance, human target, pyroelectric infrared (PIR)
      sensor, the body type, human moving velocity, signal modulation mask, and Fresnel
      lens. The mapping relationship between the sensed waveform and multiple
      influencing factors is established, and a group of mathematical models are
      deduced which fuse the macro factors and micro factors. Finally, the experimental
      results show the macro-factors indirectly affect the recognition ability of human
      based on the pyroelectric technology. At the same time, the correctness and
      effectiveness of the mathematical models is also verified, which make it easier
      to obtain more pyroelectric infrared information about the human body for
      discriminating human targets.

PMID- 29462909
TI  - Antimicrobial Peptides for Topical Treatment of Osteomyelitis and Implant-Related
      Infections: Study in the Spongy Bone.
AB  - We examined the benefits of short linear alpha-helical antimicrobial peptides
      (AMPs) invented in our laboratory for treating bone infection and preventing
      microbial biofilm formation on model implants due to causative microorganisms of
      osteomyelitis. For this purpose, we introduced a model of induced osteomyelitis
      that utilizes human femur heads obtained from the hospital after their
      replacement with artificial prostheses. We found that the focus of the infection
      set up in the spongy part of this bone treated with AMP-loaded calcium phosphate
      cement was eradicated much more effectively than was the focus treated with
      antibiotics such as vancomycin or gentamicin loaded into the same cement. This
      contradicts the minimum inhibitory concentrations (MIC) values of AMPs and
      antibiotics against some bacterial strains obtained in standard in vitro assays.
      The formation of microbial biofilm on implants made from poly(methylmethacrylate)
      based bone cement loaded with AMP was evaluated after the implants' removal from
      the infected bone sample. AMPs loaded in such model implants prevented microbial
      adhesion and subsequent formation of bacterial biofilm on their surface. Biofilms
      did form, on the other hand, on control implants made from the plain cement when
      these were implanted into the same infected bone sample. These results of the
      experiments performed in human bone tissue highlight the clinical potential of
      antimicrobial peptides for use in treating and preventing osteomyelitis caused by
      resistant pathogens.

PMID- 29462910
TI  - Dynamic Changes in Phenolics and Antioxidant Capacity during Pecan (Carya
      illinoinensis) Kernel Ripening and Its Phenolics Profiles.
AB  - Pecan (Carya illinoinensis) kernels have a high phenolics content and a high
      antioxidant capacity compared to other nuts-traits that have attracted great
      interest of late. Changes in the total phenolic content (TPC), condensed tannins
      (CT), total flavonoid content (TFC), five individual phenolics, and antioxidant
      capacity of five pecan cultivars were investigated during the process of kernel
      ripening. Ultra-performance liquid chromatography coupled with quadruple time-of
      flight mass (UPLC-Q/TOF-MS) was also used to analyze the phenolics profiles in
      mixed pecan kernels. TPC, CT, TFC, individual phenolics, and antioxidant capacity
      were changed in similar patterns, with values highest at the water or milk
      stages, lowest at milk or dough stages, and slightly varied at kernel stages.
      Forty phenolics were tentatively identified in pecan kernels, of which two were
      first reported in the genus Carya, six were first reported in Carya
      illinoinensis, and one was first reported in its kernel. The findings on these
      new phenolic compounds provide proof of the high antioxidant capacity of pecan
      kernels.

PMID- 29462912
TI  - UAVs and Machine Learning Revolutionising Invasive Grass and Vegetation Surveys
      in Remote Arid Lands.
AB  - The monitoring of invasive grasses and vegetation in remote areas is challenging,
      costly, and on the ground sometimes dangerous. Satellite and manned aircraft
      surveys can assist but their use may be limited due to the ground sampling
      resolution or cloud cover. Straightforward and accurate surveillance methods are
      needed to quantify rates of grass invasion, offer appropriate vegetation tracking
      reports, and apply optimal control methods. This paper presents a pipeline
      process to detect and generate a pixel-wise segmentation of invasive grasses,
      using buffel grass (Cenchrus ciliaris) and spinifex (Triodia sp.) as examples.
      The process integrates unmanned aerial vehicles (UAVs) also commonly known as
      drones, high-resolution red, green, blue colour model (RGB) cameras, and a data
      processing approach based on machine learning algorithms. The methods are
      illustrated with data acquired in Cape Range National Park, Western Australia
      (WA), Australia, orthorectified in Agisoft Photoscan Pro, and processed in Python
      programming language, scikit-learn, and eXtreme Gradient Boosting (XGBoost)
      libraries. In total, 342,626 samples were extracted from the obtained data set
      and labelled into six classes. Segmentation results provided an individual
      detection rate of 97% for buffel grass and 96% for spinifex, with a global
      multiclass pixel-wise detection rate of 97%. Obtained results were robust against
      illumination changes, object rotation, occlusion, background cluttering, and
      floral density variation.

PMID- 29462911
TI  - Anti-Inflammatory and Gastroprotective Roles of Rabdosia inflexa through
      Downregulation of Pro-Inflammatory Cytokines and MAPK/NF-kappaB Signaling
      Pathways.
AB  - Globally, gastric ulcer is a vital health hazard for a human. Rabdosia inflexa
      (RI) has been used in traditional medicine for inflammatory diseases. The present
      study aimed to investigate the protective effect and related molecular mechanism
      of RI using lipopolysaccharide (LPS)-induced inflammation in RAW 246.7 cells and
      HCl/EtOH-induced gastric ulcer in mice. We applied 3-(4,5-dimethyl-thiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT), nitric oxide (NO), reactive oxygen species
      (ROS), histopathology, malondialdehyde (MDA), quantitative real-time polymerase
      chain reaction (qPCR), immunohistochemistry (IHC), and Western blot analyses to
      evaluate the protective role of RI. Study revealed that RI effectively attenuated
      LPS-promoted NO and ROS production in RAW 246.7 cells. In addition, RI mitigated
      gastric oxidative stress by inhibiting lipid peroxidation, elevating NO, and
      decreasing gastric inflammation. RI significantly halted elevated gene expression
      of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6), inducible nitric oxide
      synthetase (iNOS), and cyclooxygenase-2 (COX-2) in gastric tissue. Likewise, RI
      markedly attenuated the mitogen-activated protein kinases (MAPKs)
      phosphorylation, COX-2 expression, phosphorylation and degradation of inhibitor
      kappa B (IkappaBalpha) and activation of nuclear factor kappa B (NF-kappaB).
      Thus, experimental findings suggested that the anti-inflammatory and
      gastroprotective activities of RI might contribute to regulating pro-inflammatory
      cytokines and MAPK/NF-kappaB signaling pathways.

PMID- 29462913
TI  - Working towards More Effective Implementation, Dissemination and Scale-Up of
      Lower-Limb Injury-Prevention Programs: Insights from Community Australian
      Football Coaches.
AB  - Disseminating lower-limb injury-prevention exercise programs (LL-IPEPs) with
      strategies that effectively reach coaches across sporting environments is a way
      of preventing lower-limb injuries (LLIs) and ensuring safe and sustainable sport
      participation. The aim of this study was to explore community-Australian Football
      (community-AF) coaches' perspectives on the strategies they believed would
      enhance the dissemination and scale-up of LL-IPEPs. Using a qualitative multiple
      case study design, semi-structured interviews with community-AF coaches in
      Victoria, Australia, were conducted. Overall, coaches believed a range of
      strategies were important including: coach education, policy drivers, overcoming
      potential problem areas, a 'try before you buy approach', presenting empirical
      evidence and guidelines for injury-prevention exercise programs (IPEPs), forming
      strategic collaboration and working in partnership, communication and social
      marketing, public meetings, development of a coach hotline, and targeted multi
      focused approaches. A shift to a culture whereby evidence-based IPEP practices in
      community-AF will take time, and persistent commitment by all involved in the
      sport is important. This will support the creation of strategies that will
      enhance the dissemination and scale-up of LL-IPEPs across community sport
      environments. The focus of research needs to continue to identify effective,
      holistic and multi-level interventions to support coaches in preventing LLIs.
      This could lead to the determination of successful strategies such as behavioural
      regulation strategies and emotional coping resources to implement LL-IPEPs into
      didactic curricula and practice. Producing changes in practice will require
      attention to which strategies are a priority and the most effective.

PMID- 29462914
TI  - Socioeconomic Inequality in One-Year Mortality of Elderly People with Hip
      Fracture in Taiwan.
AB  - Hip fracture commonly results in considerable consequences in terms of
      disability, mortality, long-term institutional care and cost. Taiwan launched its
      universal health insurance coverage in 1995, which largely removes financial
      barriers to health care. This study aims to investigate whether socioeconomic
      inequality in one-year mortality exists among Taiwanese elderly people. This
      population-based cohort study included 193,158 elderly patients (>=65 years)
      admitted for hip fracture between 2000 and 2012. With over a one-year follow-up,
      10.52% of the participants died from all causes. The mortality rate was low in
      the northern part of Taiwan and in urban and high-family-income areas. Multiple
      Poisson regression models further suggested that the level of >Q1-Q3 and >Q3-Max
      showed significantly reduced odds ratio of one-year mortality at 0.90 (95%
      confidence interval (CI), 0.87-0.93) and 0.77 (95% CI, 0.74-0.81), respectively,
      compared with that of the lowest family income level (i.e., Min.-Q1). Despite a
      monotonic decline in overall one-year mortality during the study period,
      socioeconomic inequality in one-year mortality rate remained evident. The annual
      percentage change in one-year mortality was higher (-2.86) in elderly people from
      families with high income (>Q3-Max.) than that for elderly patients from family
      with low income (Min.-Q1, -1.94). Accessibility, rather than affordability, to
      health care for hip fracture is probably responsible for the observed
      socioeconomic inequality.

PMID- 29462915
TI  - Pilocarpine-Induced Status Epilepticus Is Associated with P-Glycoprotein
      Induction in Cardiomyocytes, Electrocardiographic Changes, and Sudden Death.
AB  - Sudden unexpected death in epilepsy (SUDEP) is the major cause of death in those
      patients suffering from refractory epilepsy (RE), with a 24-fold higher risk
      relative to the normal population. SUDEP risk increases with seizure frequency
      and/or seizure-duration as in RE and Status Epilepticus (SE). P-glycoprotein (P
      gp), the product of the multidrug resistant ABCB1-MDR-1 gene, is a detoxifying
      pump that extrudes drugs out of the cells and can confer pharmacoresistance to
      the expressing cells. Neurons and cardiomyocytes normally do not express P-gp,
      however, it is overexpressed in the brain of patients or in experimental models
      of RE and SE. P-gp was also detected after brain or cardiac hypoxia. We have
      previously demonstrated that repetitive pentylenetetrazole (PTZ)-induced seizures
      increase P-gp expression in the brain, which is associated with membrane
      depolarization in the hippocampus, and in the heart, which is associated with
      fatal SE. SE can produce hypoxic-ischemic altered cardiac rhythm (HIACR) and
      severe arrhythmias, and both are related with SUDEP. Here, we investigate whether
      SE induces the expression of hypoxia-inducible transcription factor (HIF)-1alpha
      and P-gp in cardiomyocytes, which is associated with altered heart rhythm, and if
      these changes are related with the spontaneous death rate. SE was induced in
      Wistar rats once a week for 3 weeks, by lithium-pilocarpine-paradigm.
      Electrocardiograms, HIF-1alpha, and P-gp expression in cardiomyocytes, were
      evaluated in basal conditions and 72 h after SE. All spontaneous deaths occurred
      48 h after each SE was registered. We observed that repeated SE induced HIF
      1alpha and P-gp expression in cardiomyocytes, electrocardiographic (ECG) changes,
      and a high rate of spontaneous death. Our results suggest that the highly
      accumulated burden of convulsive stress results in a hypoxic heart insult, where
      P-gp expression may play a depolarizing role in cardiomyocyte membranes and in
      the development of the ECG changes, such as QT interval prolongation, that could
      be related with SUDEP. We postulate that this mechanism could explain, in part,
      the higher SUDEP risk in patients with RE or SE.

PMID- 29462916
TI  - Gene Environment Interactions and Predictors of Colorectal Cancer in Family
      Based, Multi-Ethnic Groups.
AB  - For the personalization of polygenic/omics-based health care, the purpose of this
      study was to examine the gene-environment interactions and predictors of
      colorectal cancer (CRC) by including five key genes in the one-carbon metabolism
      pathways. In this proof-of-concept study, we included a total of 54 families and
      108 participants, 54 CRC cases and 54 matched family friends representing four
      major racial ethnic groups in southern California (White, Asian, Hispanics, and
      Black). We used three phases of data analytics, including exploratory, family
      based analyses adjusting for the dependence within the family for sharing genetic
      heritage, the ensemble method, and generalized regression models for predictive
      modeling with a machine learning validation procedure to validate the results for
      enhanced prediction and reproducibility. The results revealed that despite the
      family members sharing genetic heritage, the CRC group had greater combined gene
      polymorphism rates than the family controls (p < 0.05), on MTHFR C677T, MTR
      A2756G, MTRR A66G, and DHFR 19 bp except MTHFR A1298C. Four racial groups
      presented different polymorphism rates for four genes (all p < 0.05) except MTHFR
      A1298C. Following the ensemble method, the most influential factors were
      identified, and the best predictive models were generated by using the
      generalized regression models, with Akaike's information criterion and leave-one
      out cross validation methods. Body mass index (BMI) and gender were consistent
      predictors of CRC for both models when individual genes versus total polymorphism
      counts were used, and alcohol use was interactive with BMI status. Body mass
      index status was also interactive with both gender and MTHFR C677T gene
      polymorphism, and the exposure to environmental pollutants was an additional
      predictor. These results point to the important roles of environmental and
      modifiable factors in relation to gene-environment interactions in the prevention
      of CRC.

PMID- 29462917
TI  - Characterization and Determination of Interesterification Markers
      (Triacylglycerol Regioisomers) in Confectionery Oils by Liquid Chromatography
      Mass Spectrometry.
AB  - Interesterification is an industrial transformation process aiming to change the
      physico-chemical properties of vegetable oils by redistributing fatty acid
      position within the original constituent of the triglycerides. In the
      confectionery industry, controlling formation degree of positional isomers is
      important in order to obtain fats with the desired properties. Silver ion HPLC
      (High Performance Liquid Chromatography) is the analytical technique usually
      adopted to separate triglycerides (TAGs) having different unsaturation degrees.
      However, separation of TAG positional isomers is a challenge when the number of
      double bonds is the same and the only difference is in their position within the
      triglyceride molecule. The TAG positional isomers involved in the present work
      have a structural specificity that require a separation method tailored to the
      needs of confectionery industry. The aim of this work was to obtain a
      chromatographic resolution that might allow reliable qualitative and quantitative
      evaluation of TAG positional isomers within reasonably rapid retention times and
      robust in respect of repeatability and reproducibility. The resulting analytical
      procedure was applied both to confectionery raw materials and final products.

PMID- 29462918
TI  - Out-of-Home Food Consumers in Brazil: What do They Eat?
AB  - Considering the increased contribution of foods consumed outside home and their
      potential impact on diet, this study aims to identify eating out patterns and
      their association with nutritional dietary quality in Brazil. We used the
      Individual Food Intake Survey 2008-2009, conducted with 34,003 individuals aged
      10 and up. We used factor analysis by principal component to identify out-of-home
      eating patterns and linear regression to explore the association between patterns
      scores and dietary quality. We identified three food patterns. The "Traditional
      meal" pattern carried more rice, beans, meat, roots and tubers, pasta, vegetables
      and eggs. The "typical Brazilian breakfast/tea" pattern carried more fresh bread,
      margarine, milk, cheese and butter. The "Ultra-processed food" pattern carried
      more ready-to-eat meals and soft drinks. The "traditional meal" pattern was
      positively associated with calories from proteins, fiber, iron, potassium and
      sodium densities, whereas "typical Brazilian breakfast/tea" and "ultra-processed
      food" patterns were positively associated with energy density, the percentage of
      calories from lipids or carbohydrates, trans fat and free sugar. Out-of-home
      eating may have a negative impact on nutritional dietary quality when based on
      ultra-processed food. However, it is possible to maintain a healthy out-of-home
      diet with adherence to traditional Brazilian cuisine.

PMID- 29462919
TI  - Probing the Influence of Linker Length and Flexibility in the Design and
      Synthesis of New Trehalase Inhibitors.
AB  - This work aims to synthesize new trehalase inhibitors selective towards the
      insect trehalase versus the porcine trehalase, in view of their application as
      potentially non-toxic insecticides and fungicides. The synthesis of a new
      pseudodisaccharide mimetic 8, by means of a stereoselective alpha-glucosylation
      of the key pyrrolizidine intermediate 13, was accomplished. The activity of
      compound 8 as trehalase inhibitor towards C.riparius trehalase was evaluated and
      the results showed that 8 was active in the MUM range and showed a good
      selectivity towards the insect trehalase. To reduce the overall number of
      synthetic steps, simpler and more flexible disaccharide mimetics 9-11 bearing a
      pyrrolidine nucleus instead of the pyrrolizidine core were synthesized. The
      biological data showed the key role of the linker chain's length in inducing
      inhibitory properties, since only compounds 9 (alpha,beta-mixture), bearing a two
      carbon atom linker chain, maintained activity as trehalase inhibitors. A proper
      change in the glucosyl donor-protecting groups allowed the stereoselective
      synthesis of the beta-glucoside 9beta, which was active in the low micromolar
      range (IC50 = 0.78 MUM) and 12-fold more potent (and more selective) than 9alpha
      towards the insect trehalase.

PMID- 29462920
TI  - The Role of the Slc39a Family of Zinc Transporters in Zinc Homeostasis in Skin.
AB  - The first manifestations that appear under zinc deficiency are skin defects such
      as dermatitis, alopecia, acne, eczema, dry, and scaling skin. Several genetic
      disorders including acrodermatitis enteropathica (also known as Danbolt-Closs
      syndrome) and Brandt's syndrome are highly related to zinc deficiency. However,
      the zinc-related molecular mechanisms underlying normal skin development and
      homeostasis, as well as the mechanism by which disturbed zinc homeostasis causes
      such skin disorders, are unknown. Recent genomic approaches have revealed the
      physiological importance of zinc transporters in skin formation and clarified
      their functional impairment in cutaneous pathogenesis. In this review, we provide
      an overview of the relationships between zinc deficiency and skin disorders,
      focusing on the roles of zinc transporters in the skin. We also discuss
      therapeutic outlooks and advantages of controlling zinc levels via zinc
      transporters to prevent cutaneous disorganization.

PMID- 29462921
TI  - Complete Chloroplast Genomes of Papaver rhoeas and Papaver orientale: Molecular
      Structures, Comparative Analysis, and Phylogenetic Analysis.
AB  - Papaver rhoeas L. and P. orientale L., which belong to the family Papaveraceae,
      are used as ornamental and medicinal plants. The chloroplast genome has been used
      for molecular markers, evolutionary biology, and barcoding identification. In
      this study, the complete chloroplast genome sequences of P. rhoeas and P.
      orientale are reported. Results show that the complete chloroplast genomes of P.
      rhoeas and P. orientale have typical quadripartite structures, which are
      comprised of circular 152,905 and 152,799-bp-long molecules, respectively. A
      total of 130 genes were identified in each genome, including 85 protein-coding
      genes, 37 tRNA genes, and 8 rRNA genes. Sequence divergence analysis of four
      species from Papaveraceae indicated that the most divergent regions are found in
      the non-coding spacers with minimal differences among three Papaver species.
      These differences include the ycf1 gene and intergenic regions, such as rpoB
      trnC, trnD-trnT, petA-psbJ, psbE-petL, and ccsA-ndhD. These regions are
      hypervariable regions, which can be used as specific DNA barcodes. This finding
      suggested that the chloroplast genome could be used as a powerful tool to resolve
      the phylogenetic positions and relationships of Papaveraceae. These results offer
      valuable information for future research in the identification of Papaver species
      and will benefit further investigations of these species.

PMID- 29462922
TI  - Differential Long-Chain Polyunsaturated Fatty Acids Status and Placental
      Transport in Adolescent Pregnancies.
AB  - Adolescent pregnancy increases risk of adverse perinatal outcomes. Placental
      delivery of long-chain polyunsaturated fatty acids (LCPUFA) is essential for
      fetal growth and development. In this pilot study, we aimed to assess maternal
      and fetal status of fatty acids (FA) measured at birth and the expression of key
      genes involved in FA uptake, transport and metabolism in the placenta of fifteen
      adolescents and fifteen adults. FA were quantified by gas-liquid chromatography.
      Placental expression of FA transporters was assessed by quantitative real-time
      polymerase chain reaction (qRT-PCR) and peroxisome proliferator-activated
      receptor gamma (PPARgamma) was quantified by Western Blot. Adolescents had lower
      docosahexaenoic acid (DHA, 22:6 n-3) and total n-3 FA levels in maternal
      erythrocytes and placenta, but these were not different in fetal erythrocytes.
      Arachidonic acid (AA, 20:4 n-6) concentration was increased in placenta but lower
      in fetal circulation. Plasma membrane fatty acid binding protein (FABPpm) and
      fatty acid transport protein (FATP) 4 mRNA expressions were not different,
      however FATP1, fatty acid translocase (FAT/CD36) and fatty acid binding protein 3
      (FABP3) mRNA and PPARgamma protein levels were decreased in placenta of
      adolescents. Despite significant downregulation of FATP1, CD36 and FABP3, there
      was only a modest decrease in LCPUFA (10%) and AA (12%) and no difference in DHA
      content in cord blood, suggesting that FA transfer to the fetus was partially
      protected by other factors in adolescents from this cohort.

PMID- 29462923
TI  - The Effect of Whey Protein Supplementation on the Temporal Recovery of Muscle
      Function Following Resistance Training: A Systematic Review and Meta-Analysis.
AB  - Whey protein (WP) is a widely consumed nutritional supplement, known to enhance
      strength and muscle mass during resistance training (RT) regimens. Muscle protein
      anabolism is acutely elevated following RT, which is further enhanced by WP. As a
      result, there is reason to suggest that WP supplementation may be an effective
      nutritional strategy for restoring the acute loss of contractile function that
      occurs following strenuous RT. This systematic review and meta-analysis provides
      a synthesis of the literature to date, investigating the effect of WP
      supplementation on the recovery of contractile function in young, healthy adults.
      Eight studies, containing 13 randomised control trials (RCTs) were included in
      this review and meta-analysis, from which individual standardised effect sizes
      (ESs) were calculated, and a temporal overall ES was determined using a random
      effects model. Whilst only half of the individual studies reported beneficial
      effects for WP, the high-quality evidence taken from the 13 RCTs was meta
      analysed, yielding overall positive small to medium effects for WP from < 24 to
      96 h (ES range = 0.4 to 0.7), for the temporal restoration of contractile
      function compared to the control treatment. Whilst the effects for WP were shown
      to be consistent over time, these results are limited to 13 RCTs, principally
      supporting the requirement for further comprehensive research in this area.

PMID- 29462925
TI  - Insufficient Fruit and Vegetable Intake in a Low- and Middle-Income Setting: A
      Population-Based Survey in Semi-Urban Tanzania.
AB  - A daily intake of 5 portions of fruit and vegetables (FV) is recommended for
      protection against non-communicable diseases (NCDs). Inadequate FV intake is a
      global problem but resource-poor countries like Tanzania are most deprived and
      constitute settings where little is known for informing public health
      interventions. This study aimed to describe the prevalence of inadequate FV
      intake, frequency of FV intake, portions of FV intake and their associations with
      socio-demographic/lifestyle factors in South-Eastern Tanzania. Data on FV dietary
      indicators, socio-demographic factors, smoking, alcohol and healthcare use were
      collected from 7953 participants (>=15 years) of the population-based MZIMA open
      community cohort (2012-2013). Multivariable logistic regression was used to
      examine associations between FV intake outcomes and their socio
      demographic/lifestyle determinants. Most (82%) of the participants did not meet
      the recommended daily FV intake While only a fraction consumed fruits daily
      (15.5%), almost half consumed vegetables daily (44.2%). However, the median (IQR)
      number of vegetable portions consumed was lower (2(1)/person/day) than that for
      fruits (2(2)/person/day) People with higher education were more likely to consume
      fruits daily. Independent correlates of inadequate FV intake included young age,
      being male, low education, low-income occupations, low alcohol, high tobacco and
      low healthcare use. Public health interventions should target the socio
      economically deprived and culturally-rooted preferences while prioritizing
      promotion of vegetable for most immediate gain in overall FV intake.

PMID- 29462924
TI  - Achieving Optimal Post-Exercise Muscle Protein Remodeling in Physically Active
      Adults through Whole Food Consumption.
AB  - Dietary protein ingestion is critical to maintaining the quality and quantity of
      skeletal muscle mass throughout adult life. The performance of acute exercise
      enhances muscle protein remodeling by stimulating protein synthesis rates for
      several hours after each bout, which can be optimized by consuming protein during
      the post-exercise recovery period. To date, the majority of the evidence
      regarding protein intake to optimize post-exercise muscle protein synthesis rates
      is limited to isolated protein sources. However, it is more common to ingest
      whole food sources of protein within a normal eating pattern. Emerging evidence
      demonstrates a promising role for the ingestion of whole foods as an effective
      nutritional strategy to support muscle protein remodeling and recovery after
      exercise. This review aims to evaluate the efficacy of the ingestion of nutrient
      rich and protein-dense whole foods to support post-exercise muscle protein
      remodeling and recovery with pertinence towards physically active people.

PMID- 29462926
TI  - Do Current Fortification and Supplementation Programs Assure Adequate Intake of
      Fat-Soluble Vitamins in Belgian Infants, Toddlers, Pregnant Women, and Lactating
      Women?
AB  - Abstracts: Adequate intakes of fat-soluble vitamins are essential to support the
      growth and development of the foetus, the neonate, and the young child. By means
      of an online self-administered frequency questionnaire, this study aimed to
      evaluate the intake of vitamins A, D, E, and K in Belgian infants (n = 455),
      toddlers (n = 265), pregnant women (n = 161), and lactating women (n = 165). The
      contribution of foods, fortified foods, and supplements on the total intake was
      quantified. 5% of toddlers, 16% of pregnant women, and 35% of lactating women had
      an inadequate vitamin A intake. Conversely, excessive vitamin A intakes were
      associated with consumption of liver (products). Furthermore, 22% of infants were
      at risk for inadequate vitamin D intake due to the lack of prophylaxis, while
      consumption of highly dosed supplements posed a risk for excessive intakes in 6%
      26% of infants. Vitamin D intake in pregnant women and lactating women was
      inadequate (median of 51%, respectively, 60% of the adequate intake). In all
      groups, the risk for inadequate intake of vitamin E and K was low. Contribution
      of fortified foods to vitamin A, D, E, and K intake was minor, except in
      toddlers. National fortification strategies should be investigated as an
      alternative or additional strategy to prevent vitamin D and A deficiency. There
      is a need to revise and set uniform supplement recommendations. Finally, non
      users of vitamin D prophylaxis need to be identified for targeted treatment.

PMID- 29462927
TI  - Separation Options for Phosphorylated Osteopontin from Transgenic Microalgae
      Chlamydomonas reinhardtii.
AB  - Correct folding and post-translational modifications are vital for therapeutic
      proteins to elicit their biological functions. Osteopontin (OPN), a bone
      regenerative protein present in a range of mammalian cells, is an acidic
      phosphoprotein with multiple potential phosphorylation sites. In this study, the
      ability of unicellular microalgae, Chlamydomonas reinhardtii, to produce
      phosphorylated recombinant OPN in its chloroplast is investigated. This study
      further explores the impact of phosphorylation and expression from a "plant-like"
      algae on separation of OPN. Chromatography resins ceramic hydroxyapatite (CHT)
      and Gallium-immobilized metal affinity chromatography (Ga-IMAC) were assessed for
      their binding specificity to phosphoproteins. Non-phosphorylated recombinant OPN
      expressed in E. coli was used to compare the specificity of interaction of the
      resins to phosphorylated OPN. We observed that CHT binds OPN by multimodal
      interactions and was better able to distinguish phosphorylated proteins in the
      presence of 250 mM NaCl. Ga-IMAC interaction with OPN was not selective to
      phosphorylation, irrespective of salt, as the resin bound OPN from both algal and
      bacterial sources. Anion exchange chromatography proved an efficient capture
      method to partially separate major phosphorylated host cell protein impurities
      such as Rubisco from OPN.

PMID- 29462929
TI  - Distributed Water Pollution Source Localization with Mobile UV-Visible
      Spectrometer Probes in Wireless Sensor Networks.
AB  - Pollution accidents that occur in surface waters, especially in drinking water
      source areas, greatly threaten the urban water supply system. During water
      pollution source localization, there are complicated pollutant spreading
      conditions and pollutant concentrations vary in a wide range. This paper provides
      a scalable total solution, investigating a distributed localization method in
      wireless sensor networks equipped with mobile ultraviolet-visible (UV-visible)
      spectrometer probes. A wireless sensor network is defined for water quality
      monitoring, where unmanned surface vehicles and buoys serve as mobile and
      stationary nodes, respectively. Both types of nodes carry UV-visible spectrometer
      probes to acquire in-situ multiple water quality parameter measurements, in which
      a self-adaptive optical path mechanism is designed to flexibly adjust the
      measurement range. A novel distributed algorithm, called Dual-PSO, is proposed to
      search for the water pollution source, where one particle swarm optimization
      (PSO) procedure computes the water quality multi-parameter measurements on each
      node, utilizing UV-visible absorption spectra, and another one finds the global
      solution of the pollution source position, regarding mobile nodes as particles.
      Besides, this algorithm uses entropy to dynamically recognize the most sensitive
      parameter during searching. Experimental results demonstrate that online multi
      parameter monitoring of a drinking water source area with a wide dynamic range is
      achieved by this wireless sensor network and water pollution sources are
      localized efficiently with low-cost mobile node paths.

PMID- 29462928
TI  - Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles:
      Physicochemical Properties and Antineoplastic Activities in Human Colorectal
      Cancer Cells In Vitro.
AB  - New strategies are being investigated to ameliorate the efficacy and reduce the
      toxicity of the drugs currently used in colorectal cancer (CRC), one of the most
      common malignancies in the Western world. Data have been accumulated
      demonstrating that the antineoplastic therapies with either conventional or
      single-targeted drugs could take advantage from a combined treatment with omega-3
      polyunsaturated fatty acids (omega-3 PUFA). These nutrients, shown to be safe at
      the dosage generally used in human trials, are able to modulate molecules
      involved in colon cancer cell growth and survival. They have also the potential
      to act against inflammation, which plays a critical role in CRC development, and
      to increase the anti-cancer immune response. In the present study, omega-3 PUFA
      were encapsulated in solid lipid nanoparticles (SLN) having a lipid matrix
      containing resveratrol esterified to stearic acid. Our aim was to increase the
      efficiency of the incorporation of these fatty acids into the cells and prevent
      their peroxidation and degradation. The Resveratrol-based SLN were characterized
      and investigated for their antioxidant activity. It was observed that the
      encapsulation of omega-3 PUFA into the SLN enhanced significantly their
      incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory
      effects in these cancer cells, mainly by reducing cell proliferation.

PMID- 29462930
TI  - Flame-Oxidized Stainless-Steel Anode as a Probe in Bioelectrochemical System
      Based Biosensors to Monitor the Biochemical Oxygen Demand of Wastewater.
AB  - Biochemical oxygen demand (BOD) is a widely used index of water quality in
      wastewater treatment; however, conventional measurement methods are time
      consuming. In this study, we analyzed a novel flame-oxidized stainless steel
      anode (FO-SSA) for use as the probe of bioelectrochemical system (BES)-based
      biosensors to monitor the BOD of treated swine wastewater. A thinner biofilm
      formed on the FO-SSA compared with that on a common carbon-cloth anode (CCA). The
      FO-SSA was superior to the CCA in terms of rapid sensing; the response time of
      the FO-SSA to obtain the value of R2 > 0.8 was 1 h, whereas the CCA required 4 h.
      These results indicate that the FO-SSA offers better performance than traditional
      CCAs in BES biosensors and can be used to improve biomonitoring of wastewater.

PMID- 29462931
TI  - Defect-Repairable Latent Feature Extraction of Driving Behavior via a Deep Sparse
      Autoencoder.
AB  - Data representing driving behavior, as measured by various sensors installed in a
      vehicle, are collected as multi-dimensional sensor time-series data. These data
      often include redundant information, e.g., both the speed of wheels and the
      engine speed represent the velocity of the vehicle. Redundant information can be
      expected to complicate the data analysis, e.g., more factors need to be analyzed;
      even varying the levels of redundancy can influence the results of the analysis.
      We assume that the measured multi-dimensional sensor time-series data of driving
      behavior are generated from low-dimensional data shared by the many types of one
      dimensional data of which multi-dimensional time-series data are composed.
      Meanwhile, sensor time-series data may be defective because of sensor failure.
      Therefore, another important function is to reduce the negative effect of
      defective data when extracting low-dimensional time-series data. This study
      proposes a defect-repairable feature extraction method based on a deep sparse
      autoencoder (DSAE) to extract low-dimensional time-series data. In the
      experiments, we show that DSAE provides high-performance latent feature
      extraction for driving behavior, even for defective sensor time-series data. In
      addition, we show that the negative effect of defects on the driving behavior
      segmentation task could be reduced using the latent features extracted by DSAE.

PMID- 29462932
TI  - Development and Characterization of Solid Lipid Nanoparticles Loaded with a
      Highly Active Doxorubicin Derivative.
AB  - Solid lipid nanoparticles (SLNs) comprise a versatile drug delivery system that
      has been developed for the treatment of a variety of diseases. The present study
      will investigate the feasibility of entrapping an active doxorubicin prodrug (a
      squalenoyl-derivative) in SLNs. The doxorubicin derivative-loaded SLNs are
      spherically shaped, have a mean diameter of 300-400 nm and show 85% w/w drug
      entrapment efficiency. The effects on cell growth of loaded SLNs, free
      doxorubicin and the prodrug have been examined using cytotoxicity and colony
      forming assays in both human ovarian cancer line A2780 wild-type and doxorubicin
      resistant cells. Further assessments as to the treatment's ability to induce cell
      death by apoptosis have been carried out by analyzing annexin-V staining and the
      activation of caspase-3. The in vitro data demonstrate that the delivery of the
      squalenoyl-doxorubicin derivative by SLNs increases its cytotoxic activity, as
      well as its apoptosis effect. This effect was particularly evident in doxorubicin
      resistant cells.

PMID- 29462933
TI  - Integrins Were Involved in Soybean Agglutinin Induced Cell Apoptosis in IPEC-J2.
AB  - Soybean agglutinin (SBA), is a non-fiber carbohydrate related protein and a major
      anti-nutritional factor. Integrins, transmembrane glycoproteins, are involved in
      many biological processes. Although recent work suggested that integrins are
      involved in SBA-induced cell-cycle alterations, no comprehensive study has
      reported whether integrins are involved in SBA-induced cell apoptosis (SCA) in
      IPEC-J2. The relationship between SBA and integrins are still unclear. We aimed
      to elucidate the effects of SBA on IPEC-J2 cell proliferation and cell apoptosis;
      to study the roles of integrins in IPEC-J2 normal cell apoptosis (NCA) and SCA;
      and to illustrate the relationship and connection type between SBA and integrins.
      Thus, IPEC-J2 cells were treated with SBA at the levels of 0, 0.125, 0.25, 0.5,
      1.0 or 2.0 mg/mL to determine cell proliferation and cell apoptosis. The cells
      were divided into control, SBA treated groups, integrin inhibitor groups, and SBA
      + integrin inhibitor groups to determine the integrin function in SCA. The
      results showed that SBA significantly (p < 0.05) lowered cell proliferation and
      induced cell apoptosis in IPEC-J2 (p < 0.05). Inhibition of any integrin type
      induced the cell apoptosis (p < 0.05) and these integrins were involved in SCA (p
      < 0.05). Even SBA had no physical connection with integrins, an association was
      detected between SBA and alpha-actinin-2 ACTN2 (integrin-binding protein).
      Additionally, SBA reduced the mRNA expression of integrins by down regulating the
      gene expression level of ACTN2. We concluded an evidence for the anti-nutritional
      mechanism of SBA by ACTN2 with integrins. Further trials are needed to prove
      whether ACTN2 is the only protein for connecting SBA with integrin.

PMID- 29462934
TI  - A Novel Interaction Between the TLR7 and a Colchicine Derivative Revealed Through
      a Computational and Experimental Study.
AB  - The Toll-Like Receptor 7 (TLR7) is an endosomal membrane receptor involved in the
      innate immune system response. Its best-known small molecule activators are
      imidazoquinoline derivatives such as imiquimod (R-837) and resiquimod (R-848).
      Recently, an interaction between R-837 and the colchicine binding site of tubulin
      was reported. To investigate the possibility of an interaction between structural
      analogues of colchicine and the TLR7, a recent computational model for the
      dimeric form of the TLR7 receptor was used to determine a possible interaction
      with a colchicine derivative called CR42-24, active as a tubulin polymerization
      inhibitor. The estimated values of the binding energy of this molecule with
      respect to the TLR7 receptor were comparable to the energies of known binders as
      reported in a previous study. The binding to the TLR7 was further assessed by
      introducing genetic transformations in the TLR7 gene in cancer cell lines and
      exposing them to the compound. A negative shift of the IC50 value in terms of
      cell growth was observed in cell lines carrying the mutated TLR7 gene. The
      reported study suggests a possible interaction between TLR7 and a colchicine
      derivative, which can be explored for rational design of new drugs acting on this
      receptor by using a colchicine scaffold for additional modifications.

PMID- 29462935
TI  - Asymmetric Synthesis of Spirooxindoles via Nucleophilic Epoxidation Promoted by
      Bifunctional Organocatalysts.
AB  - Taking into account the postulated reaction mechanism for the organocatalytic
      epoxidation of electron-poor olefins developed by our laboratory, we have
      investigated the key factors able to positively influence the H-bond network
      installed inside the substrate/catalyst/oxidizing agent. With this aim, we have:
      (i) tested a few catalysts displaying various effects that noticeably differ in
      terms of steric hindrance and electron demand; (ii) employed alpha-alkylidene
      oxindoles decorated with different substituents on the aromatic ring (11a-g), the
      exocylic double bond (11h-l), and the amide moiety (11m-v). The observed results
      suggest that the modification of the electron-withdrawing group (EWG) weakly
      conditions the overall outcomes, and conversely a strong influence is
      unambiguously ascribable to either the N-protected or N-unprotected lactam
      framework. Specifically, when the NH free substrates (11m-u) are employed, an
      inversion of the stereochemical control is observed, while the introduction of a
      Boc protecting group affords the desired product 12v in excellent
      enantioselectivity (97:3 er).

PMID- 29462937
TI  - The Role of Nano-TiO2 Lubricating Fluid on the Hot Rolled Surface and
      Metallographic Structure of SS41 Steel.
AB  - In this paper, nano-TiO2lubricating fluid was chosen as an advanced rolling
      lubricant to investigate its effect on the hot rolled surface and metallographic
      structure of SS41 steel strips. The tribological performances of nano-TiO2
      lubricating fluid were measured by a four-ball tribotester. The hot rolling
      experiments under different lubrication conditions were carried out by a four
      high rolling mill. The surface morphology, oxide scales and metallographic
      structure after hot rolling were observed using a confocal laser scanning
      microscope and scanning electron microscope (SEM), respectively. The composition
      of surface attachments was analyzed with X-ray photoelectron spectroscopy (XPS).
      The results indicate that the nano-TiO2 lubricating fluid has a better
      tribological performance. The surface defects on the hot rolled surface could be
      decreased. The phase composition of the surface still appears as a mixture of
      ferrite and pearlite. The surface of steel strips is not micro-alloyed with
      titanium as predicted. Additionally, the grain size of rolled steel strips which
      were lubricated with the nano-TiO2lubricating fluid decreased by nearly 50%,
      compared with traditional lubricating fluid. Furthermore, it was found that the
      thickness of the oxide layers on the surface reduced, whilst the Rockwell
      hardness of the oxide layers was enhanced as nano-TiO2 lubricating fluid was
      applied.

PMID- 29462938
TI  - 2D SnO2 Nanosheets: Synthesis, Characterization, Structures, and Excellent
      Sensing Performance to Ethylene Glycol.
AB  - Two dimensional (2D)SnO2 nanosheets were synthesized by a substrate-free
      hydrothermal route using sodium stannate and sodium hydroxide in a mixed solvent
      of absolute ethanol and deionized water at a lower temperature of 130  degrees C.
      The characterization results of the morphology, microstructure, and surface
      properties of the as-prepared products demonstrated that SnO2 nanosheets with a
      tetragonal rutile structure, were composed of oriented SnO2 nanoparticles with a
      diameter of 6-12 nm. The X-ray diffraction (XRD) and high-resolution transmission
      electron microscope (FETEM) results demonstrated that the dominant exposed
      surface of the SnO2 nanoparticles was (101), but not (110). The growth and
      formation was supposed to follow the oriented attachment mechanism. The SnO2
      nanosheets exhibited an excellent sensing response toward ethylene glycol at a
      lower optimal operating voltage of 3.4 V. The response to 400 ppm ethylene glycol
      reaches 395 at 3.4 V. Even under the low concentration of 5, 10, and 20 ppm, the
      sensor exhibited a high response of 6.9, 7.8, and 12.0 to ethylene glycol,
      respectively. The response of the SnO2 nanosheets exhibited a linear dependence
      on the ethylene glycol concentration from 5 to 1000 ppm. The excellent sensing
      performance was attributed to the present SnO2 nanoparticles with small size
      close to the Debye length, the larger specific surface, the high-energy exposed
      facets of the (101) surface, and the synergistic effects of the SnO2
      nanoparticles of the nanosheets.

PMID- 29462936
TI  - New Insights into the Immune Molecular Regulation of the Pathogenesis of Acute
      Respiratory Distress Syndrome.
AB  - Acute respiratory distress syndrome is an inflammatory disease characterized by
      dysfunction of pulmonary epithelial and capillary endothelial cells, infiltration
      of alveolar macrophages and neutrophils, cell apoptosis, necroptosis, NETosis,
      and fibrosis. Inflammatory responses have key effects on every phase of acute
      respiratory distress syndrome. The severe inflammatory cascades impaired the
      regulation of vascular endothelial barrier and vascular permeability. Therefore,
      understanding the relationship between the molecular regulation of immune cells
      and the pulmonary microenvironment is critical for disease management. This
      article reviews the current clinical and basic research on the pathogenesis of
      acute respiratory distress syndrome, including information on the
      microenvironment, vascular endothelial barrier and immune mechanisms, to offer a
      strong foundation for developing therapeutic interventions.

PMID- 29462939
TI  - Peripheral B-Cell Subset Distribution in Primary Antiphospholipid Syndrome.
AB  - BACKGROUND: B-cell differentiation and B-cell tolerance checkpoints may be
      different in antiphospholipid syndrome (APS) from systemic lupus erythematosus
      (SLE) and can help to understand differences between them. Our aim was to define
      alterations of B-cell subsets in patients with primary APS (pAPS) and to compare
      them with SLE patients and healthy controls (HC). METHODS: Cross-sectional study
      including three study groups: 37 patients with pAPS, 11 SLE patients, and 21 age-
      and gender-matched HC. We determined the frequencies of different B-cell subsets
      in peripheral blood naive and memory compartments. In addition, we measured serum
      B cell-activating factor (BAFF) levels and circulating pro-inflammatory
      cytokines, such as IL-6, by commercial ELISA and CBA, respectively. RESULTS:
      Patients with pAPS showed a lower percentage of immature and naive B cells than
      patients with SLE (p = 0.013 and p = 0.010, respectively) and a higher percentage
      of non-switched memory B cells than patients with SLE (p = 0.001). No differences
      either in the percentage of switched memory cells or plasma cells were found
      among the different groups. Serum BAFF levels were higher in SLE patients than in
      healthy controls and pAPS patients (p = 0.001 and p = 0.017, respectively). A
      significant increase in the serum BAFF levels was also observed in pAPS patients
      compared to HC (p = 0.047). Circulating IL-6 levels were higher in SLE and pAPS
      patients than HC (p = 0.036 and p = 0.048, respectively). A positive correlation
      was found between serum BAFF and IL-6 levels in patients with SLE but not in pAPS
      (p = 0.011). CONCLUSIONS: Our characterization of peripheral blood B-cell
      phenotypes in pAPS demonstrates different frequencies of circulating B cells at
      different stages of differentiation. These differences in the naive B-cell
      repertoire could explain the higher number and variety of autoantibodies in SLE
      patients in comparison to pAPS patients, especially in those with obstetric
      complications.

PMID- 29462941
TI  - Small-Sized Mg-Al LDH Nanosheets Supported on Silica Aerogel with Large Pore
      Channels: Textural Properties and Basic Catalytic Performance after Activation.
AB  - Layered double hydroxides (LDHs) have been widely used as an important subset of
      solid base catalysts. However, developing low-cost, small-sized LDH nanoparticles
      with enhanced surface catalytic sites remains a challenge. In this work, silica
      aerogel (SA)-supported, small-sized Mg-Al LDH nanosheets were successfully
      prepared by one-pot coprecipitation of Mg and Al ions in an alkaline suspension
      of crushed silica aerogel. The supported LDH nanosheets were uniformly dispersed
      in the SA substrate with the smallest average radial diameter of 19.2 nm and the
      thinnest average thickness of 3.2 nm, both dimensions being significantly less
      than those of the vast majority of LDH nanoparticles reported. The SA/LDH
      composites also showed large pore volume (up to 1.3 cm3.g) and pore diameter (>9
      nm), and therefore allow efficient access of reactants to the edge catalytic
      sites of LDH nanosheets. In a base-catalyzed Henry reaction of benzaldehyde with
      nitromethane, the SA/LDH catalysts showed high reactant conversions and favorable
      stability in 6 successive cycles of reactions. The low cost of the SA carrier and
      LDH precursors, easy preparation method, and excellent catalytic properties make
      these SA/LDH composites a competitive example of solid-base catalysts.

PMID- 29462940
TI  - Is the Definition of Roma an Important Matter? The Parallel Application of Self
      and External Classification of Ethnicity in a Population-Based Health Interview
      Survey.
AB  - The Roma population is typified by a poor and, due to difficulties in ethnicity
      assessment, poorly documented health status. We aimed to compare the usefulness
      of self-reporting and observer-reporting in Roma classification for surveys
      investigating differences between Roma and non-Roma populations. Both self
      reporting and observer-reporting of Roma ethnicity were applied in a population
      based health interview survey. A questionnaire was completed by 1849 people aged
      18-64 years; this questionnaire provided information on 52 indicators (morbidity,
      functionality, lifestyle, social capital, accidents, healthcare use) indicators.
      Multivariate logistic regression models controlling for age, sex, education and
      employment were used to produce indicators for differences between the self
      reported Roma (N = 124) and non-Roma (N = 1725) populations, as well as between
      observer-reported Roma (N = 179) and non-Roma populations (N = 1670). Differences
      between interviewer-reported and self-reported individuals of Roma ethnicity in
      statistical inferences were observed for only seven indicators. The self
      reporting approach was more sensitive for two indicators, and the observer
      reported assessment for five indicators. Based on our results, the self-reported
      identity can be considered as a useful approach, and the application of observer
      reporting cannot considerably increase the usefulness of a survey, because the
      differences between Roma and non-Roma individuals are much bigger than the
      differences between indicators produced by self-reported or observer-reported
      data on individuals of Roma ethnicity.

PMID- 29462942
TI  - Performance and Fouling Study of Asymmetric PVDF Membrane Applied in the
      Concentration of Organic Fertilizer by Direct Contact Membrane Distillation
      (DCMD).
AB  - This study proposes using membrane distillation (MD) as an alternative to the
      conventional multi-stage flushing (MSF) process to concentrate a semi-product of
      organic fertilizer. By applying a unique asymmetric polyvinylidene fluoride
      (PVDF) membrane, which was specifically designed for MD applications using a
      nonsolvent thermally induced phase separation (NTIPS) method, the direct contact
      membrane distillation (DCMD) performance was investigated in terms of its
      sustainability in permeation flux, fouling resistance, and anti-wetting
      properties. It was found that the permeation flux increased with increasing flow
      rate, while the top-surface facing feed mode was the preferred orientation to
      achieve 25% higher flux than the bottom-surface facing feed mode. Compared to the
      commercial polytetrafluoroethylene (PTFE) membrane, the asymmetric PVDF membrane
      exhibited excellent anti-fouling and sustainable flux, with less than 8% flux
      decline in a 15 h continuous operation, i.e., flux decreased slightly and was
      maintained as high as 74 kg.m-2.h-1 at 70  degrees C. Meanwhile, the lost flux
      was easily recovered by clean water rinsing. Overall 2.6 times concentration
      factor was achieved in 15 h MD operation, with 63.4% water being removed from the
      fertilizer sample. Further concentration could be achieved to reach the desired
      industrial standard of 5x concentration factor.

PMID- 29462943
TI  - Functional Association between Regulatory RNAs and the Annexins.
AB  - Cells respond to pathophysiological states by activation of stress-induced
      signalling. Regulatory non-coding microRNAs (miRNAs) often form stable feed
      forward loops which ensure prolongation of the signal, contributing to sustained
      activation. Members of the annexin protein family act as sensors for Ca2+, pH,
      and lipid second messengers, and regulate various signalling pathways. Recently,
      annexins were reported to participate in feedback loops, suppressing miRNA
      synthesis and attenuating stress-induced dysregulation of gene expression. They
      can directly or indirectly associate with RNAs, and are transferred between the
      cells in exosomes and shed microvesicles. The ability of annexins to recruit
      other proteins and miRNAs into exosomes implicates them in control of cell-cell
      interactions, affecting the adaptive responses and remodelling processes during
      disease. The studies summarized in this Review point to an emerging role of
      annexins in influencing the synthesis, localisation, and transfer of regulatory
      RNAs.

PMID- 29462944
TI  - Multifaceted Mechanisms of Cisplatin Resistance in Long-Term Treated Urothelial
      Carcinoma Cell Lines.
AB  - Therapeutic efficacy of cisplatin-based treatment of late stage urothelial
      carcinoma (UC) is limited by chemoresistance. To elucidate underlying mechanisms
      and to develop new approaches for overcoming resistance, we generated long-term
      cisplatin treated (LTT) UC cell lines, characterised their cisplatin response,
      and determined the expression of molecules involved in cisplatin transport and
      detoxification, DNA repair, and apoptosis. Inhibitors of metallothioneins and
      Survivin were applied to investigate their ability to sensitise towards
      cisplatin. Cell growth, proliferation, and clonogenicity were examined after
      cisplatin treatment by MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide, EdU (5-ethynyl-2'-deoxyuridine) incorporation assay, and Giemsa
      staining, respectively. Cell cycle distribution and apoptosis were quantified by
      flow cytometry. mRNA and protein expressions were measured by real-time
      quantitative (qRT)-PCR, western blot, or immunofluorescence staining. LTTs
      recovered rapidly from cisplatin stress compared to parental cells. In LTTs, to
      various extents, cisplatin exporters and metallothioneins were induced, cisplatin
      adduct levels and DNA damage were decreased, whereas expression of DNA repair
      factors and specific anti-apoptotic factors was elevated. Pharmacological
      inhibition of Survivin, but not of metallothioneins, sensitised LTTs to
      cisplatin, in an additive manner. LTTs minimise cisplatin-induced DNA damage and
      evade apoptosis by increased expression of anti-apoptotic factors. The observed
      diversity among the four LTTs highlights the complexity of cisplatin resistance
      mechanisms even within one tumour entity, explaining heterogeneity in patient
      responses to chemotherapy.

PMID- 29462945
TI  - Luminal lncRNAs Regulation by ERalpha-Controlled Enhancers in a Ligand
      Independent Manner in Breast Cancer Cells.
AB  - Estrogen receptor-alpha (ERalpha) is a ligand-inducible protein which mediates
      estrogenic hormones signaling and defines the luminal BC phenotype. Recently, we
      demonstrated that even in absence of ligands ERalpha (apoERalpha) binds chromatin
      sites where it regulates transcription of several protein-coding and lncRNA
      genes. Noteworthy, apoERalpha-regulated lncRNAs marginally overlap estrogen
      induced transcripts, thus representing a new signature of luminal BC genes. By
      the analysis of H3K27ac enrichment in hormone-deprived MCF-7 cells, we defined a
      set of Super Enhancers (SEs) occupied by apoERalpha, including one mapped in
      proximity of the DSCAM-AS1 lncRNA gene. This represents a paradigm of apoERalpha
      activity since its expression is largely unaffected by estrogenic treatment,
      despite the fact that E2 increases ERalpha binding on DSCAM-AS1 promoter. We
      validated the enrichment of apoERalpha, p300, GATA3, FoxM1 and CTCF at both DSCAM
      AS1 TSS and at its associated SE by ChIP-qPCR. Furthermore, by analyzing MCF-7
      ChIA-PET data and by 3C assays, we confirmed long range chromatin interaction
      between the SE and the DSCAM-AS1 TSS. Interestingly, CTCF and p300 binding showed
      an enrichment in hormone-depleted medium and in the presence of ERalpha,
      elucidating the dynamics of the estrogen-independent regulation of DSCAM-AS1
      expression. The analysis of this lncRNA provides a paradigm of transcriptional
      regulation of a luminal specific apoERalpha regulated lncRNA.

PMID- 29462946
TI  - A Biochemical Approach to Detect Oxidative Stress in Infertile Women Undergoing
      Assisted Reproductive Technology Procedures.
AB  - Oxidative stress plays a major role in critical biological processes in human
      reproduction. However, a reliable and biologically accurate indicator of this
      condition does not yet exist. On these bases, the aim of this study was to assess
      and compare the blood and follicular fluid (FF) redox status of 45 infertile
      subjects (and 45 age-matched controls) undergoing in vitro fertilization (IVF),
      and explore possible relationships between the assessed redox parameters and IVF
      outcomes. Reactive Oxygen Species (ROS) production, assessed by flow cytometry
      analysis in blood leukocytes and granulosa cells, significantly increased (p <
      0.05) in infertile patients. Also, oxidative stress markers-ThioBarbituric Acid
      Reactive Substances (TBARS) as an index of lipid peroxidation, and Oxygen Radical
      Absorbance Capacity (ORAC) to account for total antioxidant capacity, both
      assayed by fluorometric procedures-in blood and FF were significantly (p < 0.001)
      modified in infertile patients compared to the control group. Moreover, a
      significant correlation between blood redox markers and FF redox markers was
      evident. An ORAC/TBARS ratio, defined as the redox index (RI), was obtained in
      the plasma and FF of the patients and controls. In the patients, the plasma RI
      was about 3.4-fold (p < 0.0001) lower than the control, and the FF RI was about
      six-fold (p < 0.0001) lower than the control. Interestingly, both the plasma RI
      and FF RI results were significantly correlated (p < 0.05) to the considered
      outcome parameters (metaphase II, fertilization rate, and ongoing pregnancies).
      Given the reported findings, a strict monitoring of redox parameters in assisted
      reproductive techniques and infertility management is recommended.

PMID- 29462947
TI  - Immunogenic Apoptosis as a Novel Tool for Anticancer Vaccine Development.
AB  - Immunogenic apoptosis, or more appropriately called immunogenic cell death (ICD),
      is a recently described form of apoptosis induced by a specific set of
      chemotherapeutic drugs or by physical therapeutic modalities, such as ionizing
      irradiation and photodynamic therapy. The peculiar characteristic of ICD is the
      ability to favor recognition and elimination of dying tumor cells by phagocytes
      in association with the release of pro-inflammatory molecules (such as cytokines
      and high-mobility group box-1). While in vitro and animal models pointed to ICD
      as one of the molecular mechanisms mediating the clinical efficacy of some
      anticancer agents, it is hard to clearly demonstrate its contribution in cancer
      patients. Clinical evidence suggests that the induction of ICD alone is possibly
      not sufficient to fully subvert the immunosuppressive tumor microenvironment.
      However, interesting results from recent studies contemplate the exploitation of
      ICD for improving the immunogenicity of cancer cells to use them as an antigen
      cargo in the development of dendritic cell (DC) vaccines. Herein, we discuss the
      effects of danger signals expressed or released by cancer cells undergoing ICD on
      the maturation and activation of immature and mature DC, highlighting the
      potential added value of ICD in adoptive immunotherapy protocols.

PMID- 29462949
TI  - The Use of Biomass for Electricity Generation: A Scoping Review of Health Effects
      on Humans in Residential and Occupational Settings.
AB  - The utilization of biomass for power generation has become more prevalent
      globally. To survey the status of evidence concerning resulting health impacts
      and to depict potential research needs, a scoping-review was conducted. Biomass
      life cycle phases of interest were the conversion and combustion phases. Studies
      from occupational and residential settings were considered. The scoping review
      was conducted systematically, comprising an extensive literature search, a guided
      screening process, in-duplicate data extraction, and critical appraisal. Two
      reviewers executed most review steps. Nine articles of relevance were identified.
      In occupational settings of biomass plants, exposure to endotoxins and fungi
      might be associated with respiratory disorders. An accidental leakage of hydrogen
      sulfide in biogas plants may lead to fatalities or severe health impacts. Living
      near biomass power plants (and the accompanied odorous air pollution) may result
      in an increased risk for several symptoms and odor annoyance, mediated by
      perception about air pollution or an evaluation of a resulting health risk. The
      methodological quality of included studies varied a lot. Overall, the body of
      evidence on the topic is sparse and future high-quality research is strongly
      recommended.

PMID- 29462948
TI  - Microfluidic Devices for Drug Delivery Systems and Drug Screening.
AB  - Microfluidic devices present unique advantages for the development of efficient
      drug carrier particles, cell-free protein synthesis systems, and rapid techniques
      for direct drug screening. Compared to bulk methods, by efficiently controlling
      the geometries of the fabricated chip and the flow rates of multiphase fluids,
      microfluidic technology enables the generation of highly stable, uniform,
      monodispersed particles with higher encapsulation efficiency. Since the existing
      preclinical models are inefficient drug screens for predicting clinical outcomes,
      microfluidic platforms might offer a more rapid and cost-effective alternative.
      Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D
      platforms mimic the in vivo cell systems in a simple, inexpensive manner, which
      allows high throughput and multiplexed drug screening at the cell, organ, and
      whole-body levels. In this review, the generation of appropriate drug or gene
      carriers including different particle types using different configurations of
      microfluidic devices is highlighted. Additionally, this paper discusses the
      emergence of fabricated microfluidic cell-free protein synthesis systems for
      potential use at point of care as well as cell-, organ-, and human-on-a-chip
      models as smart, sensitive, and reproducible platforms, allowing the
      investigation of the effects of drugs under conditions imitating the biological
      system.

PMID- 29462950
TI  - Microbiome Data Accurately Predicts the Postmortem Interval Using Random Forest
      Regression Models.
AB  - Death investigations often include an effort to establish the postmortem interval
      (PMI) in cases in which the time of death is uncertain. The postmortem interval
      can lead to the identification of the deceased and the validation of witness
      statements and suspect alibis. Recent research has demonstrated that microbes
      provide an accurate clock that starts at death and relies on ecological change in
      the microbial communities that normally inhabit a body and its surrounding
      environment. Here, we explore how to build the most robust Random Forest
      regression models for prediction of PMI by testing models built on different
      sample types (gravesoil, skin of the torso, skin of the head), gene markers (16S
      ribosomal RNA (rRNA), 18S rRNA, internal transcribed spacer regions (ITS)), and
      taxonomic levels (sequence variants, species, genus, etc.). We also tested
      whether particular suites of indicator microbes were informative across different
      datasets. Generally, results indicate that the most accurate models for
      predicting PMI were built using gravesoil and skin data using the 16S rRNA
      genetic marker at the taxonomic level of phyla. Additionally, several phyla
      consistently contributed highly to model accuracy and may be candidate indicators
      of PMI.

PMID- 29462951
TI  - Ionic Liquid-Promoted Synthesis of Novel Chromone-Pyrimidine Coupled Derivatives,
      Antimicrobial Analysis, Enzyme Assay, Docking Study and Toxicity Study.
AB  - Herein, we report an environmentally friendly, rapid, and convenient ionic liquid
      ([Et3NH][HSO4])-promoted facile synthesis of ethyl 4-(6-substituted-4-oxo-4H
      chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
      derivatives 4(a-f) and 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2
      thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5- carbohydrazide derivatives 6(a-f). All
      the synthesized derivatives 4(a-f) and 6(a-f) were evaluated for their in vitro
      antifungal and antibacterial activity, by method recommended by National
      Committee for Clinical Laboratory Standards (NCCLS). The compound 6c bearing a
      fluoro group on the chromone ring and oxygen and a hydrazino group (-NHNH2) on
      the pyrimidine ring, was found to be the most potent antibacterial compound
      amongst the synthesized derivatives. The compound 6f bearing a methoxy group (
      OCH3) on the chromone ring and sulphur group on the pyrimidine ring, was found to
      exhibit equipotent antifungal activity when compared with the standard drug
      miconazole. A D-alanine-D-alanine ligase (DdlB) enzyme assay study and an
      ergosterol extraction and quantitation assay study were performed to predict the
      mode of action of the synthesized compounds. A molecular docking study was
      performed to predict the binding interactions with receptors and mode of action
      of the synthesized derivatives. Further, analysis of the ADMET parameters for the
      synthesized compounds has shown that these compounds have good oral drug-like
      properties and can be developed as oral drug candidates. To establish the
      antimicrobial selectivity and safety, the most active compounds 6c and 6f were
      further tested for cytotoxicity against the human cancer cell line HeLa and were
      found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was
      also performed for the most active compounds 6c and 6f and the results indicated
      that the compounds are non-toxic in nature.

PMID- 29462952
TI  - Impact of Selenium Addition to Animal Feeds on Human Selenium Status in Serbia.
AB  - Research conducted during the 1980s demonstrated Se deficiency in humans.
      Increased inclusion of selenium in animal feeds started from the year 2000
      onwards. The aim of this study was to estimate the effects of selenium inclusion
      in animal feeds on human selenium status and dietary habits of the Serbian
      population related to food of animal origin. Plasma selenium concentration in
      healthy adult volunteers, including residents of one of the regions with the
      lowest (Eastern Serbia, n = 60) and of one of the regions with the highest Se
      serum levels reported in the past (Belgrade, n = 82), was determined by hydride
      generation atomic absorption spectrometry. Multivariate analysis was employed to
      determine the correlation between Se plasma levels and dietary intake data
      derived from food frequency questionnaires and laboratory tests. The mean plasma
      Se level of the participants was 84.3 +/- 15.9 MUg/L (range: 47.3-132.1 MUg/L),
      while 46% of participants had plasma Se levels lower than 80 MUg/L. Frequency of
      meat, egg, and fish consumption was significantly correlated with plasma selenium
      level (r = 0.437, p = 0.000). Selenium addition to animal feed in the quantity of
      0.14 mg/kg contributed to the improvement of human plasma selenium levels by
      approximately 30 MUg/L.

PMID- 29462953
TI  - Recent Advances in Active Infrared Thermography for Non-Destructive Testing of
      Aerospace Components.
AB  - Active infrared thermography is a fast and accurate non-destructive evaluation
      technique that is of particular relevance to the aerospace industry for the
      inspection of aircraft and helicopters' primary and secondary structures, aero
      engine parts, spacecraft components and its subsystems. This review provides an
      exhaustive summary of most recent active thermographic methods used for aerospace
      applications according to their physical principle and thermal excitation
      sources. Besides traditional optically stimulated thermography, which uses
      external optical radiation such as flashes, heaters and laser systems, novel
      hybrid thermographic techniques are also investigated. These include ultrasonic
      stimulated thermography, which uses ultrasonic waves and the local damage
      resonance effect to enhance the reliability and sensitivity to micro-cracks, eddy
      current stimulated thermography, which uses cost-effective eddy current
      excitation to generate induction heating, and microwave thermography, which uses
      electromagnetic radiation at the microwave frequency bands to provide rapid
      detection of cracks and delamination. All these techniques are here analysed and
      numerous examples are provided for different damage scenarios and aerospace
      components in order to identify the strength and limitations of each
      thermographic technique. Moreover, alternative strategies to current external
      thermal excitation sources, here named as material-based thermography methods,
      are examined in this paper. These novel thermographic techniques rely on
      thermoresistive internal heating and offer a fast, low power, accurate and
      reliable assessment of damage in aerospace composites.

PMID- 29462954
TI  - Autism Treatment Evaluation Checklist (ATEC) Norms: A "Growth Chart" for ATEC
      Score Changes as a Function of Age.
AB  - Most early-intervention Autism Spectrum Disorder (ASD) clinical trials are
      limited by the availability of psychometric technicians who assess each child's
      abilities before and after therapeutic intervention. If parents could administer
      regular psychometric evaluations of their children, then the cost of clinical
      trials will be reduced, enabling longer clinical trials with the larger number of
      participants. The Autism Treatment Evaluation Checklist (ATEC) was designed
      nearly two decades ago to provide such a tool, but the norms on the longitudinal
      changes in ATEC in the "treatment as usual" population were lacking. Here we
      report the norms of the observational cohort who voluntarily completed ATEC
      evaluations over the period of four years from 2013 to 2017.

PMID- 29462955
TI  - Liposomal Formulations for an Efficient Encapsulation of Epigallocatechin-3
      gallate: An in- Silico/Experimental Approach.
AB  - As a part of research project aimed to optimize antioxidant delivery, here we
      studied the influence of both salts and lipid matrix composition on the
      interaction of epigallocatechin-3-gallate (EGCG) with bilayer leaflets. Thus, we
      combined in silico and experimental methods to study the ability of neutral and
      anionic vesicles to encapsulate EGCG in the presence of Ca2+ and Mg2+ divalent
      salts. Experimental and in silico results show a very high correlation, thus
      confirming the efficiency of the developed methodology. In particular, we found
      out that the presence of calcium ions hinders the insertion of EGCG in the
      liposome bilayer in both neutral and anionic systems. On the contrary, the
      presence of MgCl2 improves the insertion degree of EGCG molecules respect to the
      liposomes without divalent salts. The best and most efficient salt concentration
      is that corresponding to a 5:1 molar ratio between Mg2+ and EGCG, in both neutral
      and anionic vesicles. Concerning the lipid matrix composition, the anionic one
      results in better promotion of the catechin insertion within the bilayer since
      experimentally we achieved 100% EGCG encapsulation in the lipid carrier in the
      presence of a 5:1 molar ratio of magnesium. Thus, the combination of this anionic
      liposomal formulation with magnesium chloride, avoids time-consuming separation
      steps of unentrapped active principle and appears particularly suitable for EGCG
      delivery applications.

PMID- 29462956
TI  - Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A
      Twin Drug Approach.
AB  - The synthesis of five novel homodimers is reported based on the
      anilinoisoquinolinequinone scaffold. In these twin-drug derivatives, two units of
      the anilinoquinone pharmacophores are linked through a methylene spacer. The
      formation of dimers was achieved by reaction of isoquinolinequinones with 4, 4'
      diaminodiphenylmethane via a sequence of two oxidative amination reactions. A
      preliminary in vitro screening of the homodimers reveals moderate to high
      cytotoxic activities against MDA-MB-21 breast adenocarcinoma and B16-F10 murine
      metastatic melanoma cell lines. The asymmetrical homodimer 15 stands out due to
      its cytotoxic potencies at submicromolar concentrations and high selectivity
      index (mean IC50 = 0.37 MUM; SI = 6.97) compared to those of etoposide (mean IC50
      = 3.67; SI = 0.32) and taxol (mean IC50 = 0.35; SI = 0.91) employed as reference
      anticancer drugs.

PMID- 29462957
TI  - An Advanced IoT-based System for Intelligent Energy Management in Buildings.
AB  - The energy sector is closely interconnected with the building sector and
      integrated Information and Communication Technologies (ICT) solutions for
      effective energy management supporting decision-making at building, district and
      city level are key fundamental elements for making a city Smart. The available
      systems are designed and intended exclusively for a predefined number of cases
      and systems without allowing for expansion and interoperability with other
      applications that is partially due to the lack of semantics. This paper presents
      an advanced Internet of Things (IoT) based system for intelligent energy
      management in buildings. A semantic framework is introduced aiming at the unified
      and standardised modelling of the entities that constitute the building
      environment. Suitable rules are formed, aiming at the intelligent energy
      management and the general modus operandi of Smart Building. In this context, an
      IoT-based system was implemented, which enhances the interactivity of the
      buildings' energy management systems. The results from its pilot application are
      presented and discussed. The proposed system extends existing approaches and
      integrates cross-domain data, such as the building's data (e.g., energy
      management systems), energy production, energy prices, weather data and end
      users' behaviour, in order to produce daily and weekly action plans for the
      energy end-users with actionable personalised information.

PMID- 29462958
TI  - Effect of Apium graveolens Extract Administration on the Pharmacokinetics of
      Captopril in the Plasma of Rats.
AB  - Apium graveolens (celery) is an edible and traditionally medicinal plant that is
      used worldwide, among others for the treatment of hypertension. Combining celery
      with antihypertensive drugs can affect the pharmacodynamics and pharmacokinetics
      of the latter drugs. The aim of the study is to assess the effects of
      administrating the celery extract on captopril pharmacokinetics. Sprague-Dawley
      strain rats were divided into two groups (n = 6). Group I was given captopril (10
      mg/kg Body Weight (BW)) orally, while Group II was pretreated with celery extract
      orally (40 mg/kg BW) an hour before administration of captopril. The blood
      samples were withdrawn at various intervals after drug administration. The
      captopril concentration was determined using liquid chromatography-mass
      spectrometry (LC-MS/MS) and from the blood data, the values of Ke, Cmax, Tmax,
      T1/2, and area under the curve (AUC) were calculated. The results showed that
      oral administration of the celery extract increased Cmax (38.67%), T1/2 (37.84%),
      and AUC (58.10%) and decreased Ke (27.45%) of captopril in Group II (celery +
      captopril) compared with Group I (captopril). In conclusion, celery extract can
      alter the pharmacokinetic of captopril when given in combination. The combination
      might be beneficial for the treatment of hypertension, as celery causes an
      increase in the plasma level of captopril, which can enhance its efficacy.

PMID- 29462959
TI  - Controlled and Efficient Polymerization of Conjugated Polar Alkenes by Lewis
      Pairs Based on Sterically Hindered Aryloxide-Substituted Alkylaluminumitle.
AB  - Reported herein is the development of an effective strategy for controlled and
      efficient Lewis pair polymerization of conjugated polar alkenes, including methyl
      methacrylate (MMA), n-butyl methacrylate (nBuMA), and gamma-methyl-alpha
      methylene-gamma-butyrolactone (gammaMMBL), by the utilization of sterically
      encumbered Al(BHT)2Me (BHT: 2,6-di-tert-butyl-4-methylphenol) as a Lewis acid
      that shuts down intramolecular backbiting termination. In combination with a
      selected N-heterocyclic carbene (NHC) as a Lewis base, the polymerization of MMA
      exhibited activity up to 3000 h-1 TOF and an acceptable initiation efficiency of
      60.6%, producing polymers with high molecular weight (Mn up to 130 kg/mol) and
      extremely narrow dispersity (D = 1.06~1.13). This controlled polymerization with
      a living characteristic has been evidenced by chain-extension experiments and
      chain-end analysis, and enabled the synthesis of well-defined diblock copolymers.

PMID- 29462961
TI  - A Phase I/II Study Targeting Angiogenesis Using Bevacizumab Combined with
      Chemotherapy and a Histone Deacetylase Inhibitor (Valproic Acid) in Advanced
      Sarcomas.
AB  - Epigenetic events and genetic alterations under the control of the tumor
      microenvironment potentially mediate tumor induced angiogenesis involved in soft
      tissue sarcoma (STS) metastasis. Addition of antiangiogenic agent, such as
      bevacizumab, to standard chemotherapy in treatment of sarcoma has been studied in
      clinical trials, but most of the findings have not supported its use. We
      hypothesized the existence of an epigenetically mediated "angiogenic switch", and
      the tumor microenvironment, prevents bevacizumab from truly blocking
      angiogenesis. The addition of valproic acid (VPA), a weak histone deacetylase
      inhibitor, and bevacizumab, a monoclonal antibody against vascular endothelial
      growth factor, together with the cytotoxic effects of gemcitabine and docetaxel,
      may enhance responses and alter chemoresistance. This was designed as a phase
      I/II trial with primary endpoints including safety of the treatment combination
      and tumor response. Unresectable or metastatic sarcoma patients >18 years of age,
      irrespective of number of prior treatments, received VPA 40 mg/kg orally for 5
      days prior to day 1, bevacizumab at 15 mg/kg IV on day 1, gemcitabine 900 mg/m2
      (day 1, day 8), and docetaxel 75 mg/m2 (day 8). Cycles were of 28 day duration.
      Bevacizumab and VPA were continued as maintenance after 6 cycles, until disease
      progression. A standard 3 + 3 phase I dose de-escalation design was utilized to
      evaluate safety. Gain of function p53 gene mutation testing was performed on
      available archival tissue specimens. A total of 46 patients (30 female, 16 male)
      with median age of 60 (range 24-81) years were enrolled; 34 (73.9%) patients
      received prior chemotherapy, 14 (30%) of which received prior gemcitabine and
      docetaxel. Patients received a median of 5.5 cycles (range 0-24 of treatment (min
      0, one patient died prior to completing the first cycle; max: 24, one patient
      received 6 cycles and 18 maintenance cycles before progressing). Seventeen
      patients underwent dose reduction, of which VPA was reduced in 6 patients. Forty
      one patients were evaluable for response. There was a confirmed complete response
      in 1 (epithelioid sarcoma), and a partial response (PR) in 6 (1 carcinosarcoma, 2
      extrauterine leiomyosarcoma (LMS), 2 undifferentiated pleomorphic sarcoma, and 1
      uterine LMS) patients. Stable disease (SD) was seen in 21 patients for at least 2
      months. One subject with prior gemcitabine and docetaxel had PR, and 7 had SD.
      Median progression-free survival (PFS) was 5.7 months (95% CI: 2.1-8.0), and
      overall survival (OS) was 12.9 months (95% CI: 8.3-14.5). Three patients died due
      to tumor progression while on the study. The combination of VPA, bevacizumab,
      gemcitabine, and docetaxel appears to be moderately safe and well tolerated.
      Given that there are very limited options for patients with relapsed refractory
      STS, this drug combination may be an important therapy to consider. This
      combination treatment deserves further investigation in epithelioid and
      carcinosarcoma subtypes.

PMID- 29462962
TI  - Gaofen-3 PolSAR Image Classification via XGBoost and Polarimetric Spatial
      Information.
AB  - The launch of the Chinese Gaofen-3 (GF-3) satellite will provide enough synthetic
      aperture radar (SAR) images with different imaging modes for land cover
      classification and other potential usages in the next few years. This paper aims
      to propose an efficient and practical classification framework for a GF-3
      polarimetric SAR (PolSAR) image. The proposed classification framework consists
      of four simple parts including polarimetric feature extraction and stacking, the
      initial classification via XGBoost, superpixels generation by statistical region
      merging (SRM) based on Pauli RGB image, and a post-processing step to determine
      the label of a superpixel by modified majority voting. Fast initial
      classification via XGBoost and the incorporation of spatial information via a
      post-processing step through superpixel-based modified majority voting would
      potentially make the method efficient in practical use. Preliminary experimental
      results on real GF-3 PolSAR images and the AIRSAR Flevoland data set validate the
      efficacy and efficiency of the proposed classification framework. The results
      demonstrate that the quality of GF-3 PolSAR data is adequate enough for
      classification purpose. The results also show that the incorporation of spatial
      information is important for overall performance improvement.

PMID- 29462960
TI  - The Role of Wnt Signal in Glioblastoma Development and Progression: A Possible
      New Pharmacological Target for the Therapy of This Tumor.
AB  - Wnt is a complex signaling pathway involved in the regulation of crucial
      biological functions such as development, proliferation, differentiation and
      migration of cells, mainly stem cells, which are virtually present in all
      embryonic and adult tissues. Conversely, dysregulation of Wnt signal is
      implicated in development/progression/invasiveness of different kinds of tumors,
      wherein a certain number of multipotent cells, namely "cancer stem cells", are
      characterized by high self-renewal and aggressiveness. Hence, the pharmacological
      modulation of Wnt pathway could be of particular interest, especially in tumors
      for which the current standard therapy results to be unsuccessful. This might be
      the case of glioblastoma multiforme (GBM), one of the most lethal, aggressive and
      recurrent brain cancers, probably due to the presence of highly malignant GBM
      stem cells (GSCs) as well as to a dysregulation of Wnt system. By examining the
      most recent literature, here we point out several factors in the Wnt pathway that
      are altered in human GBM and derived GSCs, as well as new molecular strategies or
      experimental drugs able to modulate/inhibit aberrant Wnt signal. Altogether,
      these aspects serve to emphasize the existence of alternative pharmacological
      targets that may be useful to develop novel therapies for GBM.

PMID- 29462963
TI  - Secreted and Tissue miRNAs as Diagnosis Biomarkers of Malignant Pleural
      Mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor that
      originates in the pleura, is diagnosed in advanced stages and has a poor
      prognosis. Accurate diagnosis of MPM is often difficult and complex, and the gold
      standard diagnosis test is based on qualitative analysis of markers in pleural
      tissue by immunohistochemical staining. Therefore, it is necessary to develop
      quantitative and non-subjective alternative diagnostic tools. MicroRNAs are non
      coding RNAs that regulate essential cellular mechanisms at the post
      transcriptional level. Recent evidence indicates that miRNA expression in tissue
      and body fluids is aberrant in various tumors, revealing miRNAs as promising
      diagnostic biomarkers. This review summarizes evidence regarding secreted and
      tissue miRNAs as biomarkers of MPM and the biological characteristics associated
      with their potential diagnostic value. In addition to studies regarding miRNAs
      with potential diagnostic value for MPM, studies that aimed to identify the
      miRNAs involved in molecular mechanisms associated with MPM development are
      described with an emphasis on relevant aspects of the experimental designs that
      may influence the accuracy, consistency and real diagnostic value of currently
      reported data.

PMID- 29462964
TI  - Behavior of the E-E' Bonds (E, E' = S and Se) in Glutathione Disulfide and
      Derivatives Elucidated by Quantum Chemical Calculations with the Quantum Theory
      of Atoms-in-Molecules Approach.
AB  - The nature of the E-E' bonds (E, E' = S and Se) in glutathione disulfide (1) and
      derivatives 2-3, respectively, was elucidated by applying quantum theory of atoms
      in-molecules (QTAIM) dual functional analysis (QTAIM-DFA), to clarify the basic
      contribution of E-E' in the biological redox process, such as the glutathione
      peroxidase process. Five most stable conformers a-e were obtained, after applying
      the Monte-Carlo method then structural optimizations. In QTAIM-DFA, total
      electron energy densities Hb(rc) are plotted versus Hb(rc) - Vb(rc)/2 at bond
      critical points (BCPs), where Vb(rc) are potential energy densities at BCPs. Data
      from the fully optimized structures correspond to the static nature. Those
      containing perturbed structures around the fully optimized one in the plot
      represent the dynamic nature of interactions. The behavior of E-E' was examined
      carefully. Whereas E-E' in 1a-3e were all predicted to have the weak covalent
      nature of the shared shell interactions, two different types of S-S were detected
      in 1, depending on the conformational properties. Contributions from the
      intramolecular non-covalent interactions to stabilize the conformers were
      evaluated. An inverse relationship was observed between the stability of a
      conformer and the strength of E-E' in the conformer, of which reason was
      discussed.

PMID- 29462965
TI  - Patterns of Protein Food Intake Are Associated with Nutrient Adequacy in the
      General French Adult Population.
AB  - Protein food intake appears to partially structure dietary patterns, as most
      current emergent diets (e.g., vegetarian and flexitarian) can be described
      according to their levels of specific protein sources. However, few data are
      available on dietary protein patterns in the general population and their
      association with nutrient adequacy. Based on protein food intake data concerning
      1678 adults from a representative French national dietary survey, and non
      negative-matrix factorization followed by cluster analysis, we were able to
      identify distinctive dietary protein patterns and compare their nutrient adequacy
      (using PANDiet probabilistic scoring). The findings revealed eight patterns that
      clearly discriminate protein intakes and were characterized by the intakes of one
      or more specific protein foods: 'Processed meat', 'Poultry', 'Pork',
      'Traditional', 'Milk', 'Take-away', 'Beef' and 'Fish'. 'Fish eaters' and 'Milk
      drinkers' had the highest overall nutrient adequacy, whereas that of 'Pork' and
      'Take-away eaters' was the lowest. Nutrient adequacy could often be accounted for
      by the characteristics of the food contributing to protein intake: 'Meat eaters'
      had high probability of adequacy for iron and zinc, for example. We concluded
      that protein patterns constitute strong elements in the background structure of
      the dietary intake and are associated with the nutrient profile that they convey.

PMID- 29462966
TI  - Optimal Scheduling and Fair Service Policy for STDMA in Underwater Networks with
      Acoustic Communications.
AB  - In this work, a multi-hop string network with a single sink node is analyzed. A
      periodic optimal scheduling for TDMA operation that considers the characteristic
      long propagation delay of the underwater acoustic channel is presented. This
      planning of transmissions is obtained with the help of a new geometrical method
      based on a 2D lattice in the space-time domain. In order to evaluate the
      performance of this optimal scheduling, two service policies have been compared:
      FIFO and Round-Robin. Simulation results, including achievable throughput, packet
      delay, and queue length, are shown. The network fairness has also been quantified
      with the Gini index.

PMID- 29462968
TI  - Feature-Level Fusion of Surface Electromyography for Activity Monitoring.
AB  - Surface electromyography (sEMG) signals are commonly used in activity monitoring
      and rehabilitation applications as they reflect effectively the motor intentions
      of users. However, real-time sEMG signals are non-stationary and vary to a large
      extent within the time frame of signals. Although previous studies have focused
      on the issues, their results have not been satisfactory. Therefore, we present a
      new method of conducting feature-level fusion to obtain a new feature space for
      sEMG signals. Eight activities of daily life (ADLs), including falls, were
      performed to obtain raw data from EMG signals from the lower limb. A feature set
      combining the time domain, time-frequency domain, and entropy domain was applied
      to the raw data to establish an initial feature space. A new projection method,
      the weighting genetic algorithm for GCCA (WGA-GCCA), was introduced to obtain the
      final feature space. Different tests were carried out to evaluate the performance
      of the new feature space. The new feature space created with the WGA-GCCA
      effectively reduced the dimensions and selected the best feature vectors
      dynamically while improving monotonicity. The Davies-Bouldin index (DBI) based on
      fuzzy c-means algorithms of the space obtained the lowest value compared with
      several fusion methods. It also achieved the highest accuracy when applied to
      support vector machine classifier.

PMID- 29462967
TI  - Overexpression of Receptor Tyrosine Kinase EphB4 Triggers Tumor Growth and
      Hypoxia in A375 Melanoma Xenografts: Insights from Multitracer Small Animal
      Imaging Experiments.
AB  - Experimental evidence has associated receptor tyrosine kinase EphB4 with tumor
      angiogenesis also in malignant melanoma. Considering the limited in vivo data
      available, we have conducted a systematic multitracer and multimodal imaging
      investigation in EphB4-overexpressing and mock-transfected A375 melanoma
      xenografts. Tumor growth, perfusion, and hypoxia were investigated by positron
      emission tomography. Vascularization was investigated by fluorescence imaging in
      vivo and ex vivo. The approach was completed by magnetic resonance imaging,
      radioluminography ex vivo, and immunohistochemical staining for blood and lymph
      vessel markers. Results revealed EphB4 to be a positive regulator of A375
      melanoma growth, but a negative regulator of tumor vascularization. Resulting in
      increased hypoxia, this physiological characteristic is considered as highly
      unfavorable for melanoma prognosis and therapy outcome. Lymphangiogenesis, by
      contrast, was not influenced by EphB4 overexpression. In order to distinguish
      between EphB4 forward and EphrinB2, the natural EphB4 ligand, reverse signaling a
      specific EphB4 kinase inhibitor was applied. Blocking experiments show EphrinB2
      reverse signaling rather than EphB4 forward signaling to be responsible for the
      observed effects. In conclusion, functional expression of EphB4 is considered a
      promising differentiating characteristic, preferentially determined by non
      invasive in vivo imaging, which may improve personalized theranostics of
      malignant melanoma.

PMID- 29462969
TI  - Milk: An Effective Recovery Drink for Female Athletes.
AB  - Milk has become a popular post-exercise recovery drink. Yet the evidence for its
      use in this regard comes from a limited number of investigations utilising very
      specific exercise protocols, and mostly with male participants. Therefore, the
      aim of this study was to investigate the effects of post-exercise milk
      consumption on recovery from a sprinting and jumping protocol in female team
      sport athletes. Eighteen females participated in an independent-groups design.
      Upon completion of the protocol participants consumed 500 mL of milk (MILK) or
      500 mL of an energy-matched carbohydrate (CHO) drink. Muscle function (peak
      torque, rate of force development (RFD), countermovement jump (CMJ), reactive
      strength index (RSI), sprint performance), muscle soreness and tiredness,
      symptoms of stress, serum creatine kinase (CK) and high-sensitivity C-reactive
      protein (hsCRP) were determined pre- and 24 h, 48 h and 72 h post-exercise. MILK
      had a very likely beneficial effect in attenuating losses in peak torque (180?/s)
      from baseline to 72 h (0.0 +/- 10.0% vs. -8.7 +/- 3.7%, MILK v CHO), and
      countermovement jump (-1.1 +/- 5.2% vs. -10.4 +/- 6.7%) and symptoms of stress (
      13.5 +/- 7.4% vs. -18.7 +/- 11.0%) from baseline to 24 h. MILK had a likely
      beneficial effect and a possibly beneficial effect on other peak torque measures
      and 5 m sprint performance at other timepoints but had an unclear effect on 10
      and 20 m sprint performance, RSI, muscle soreness and tiredness, CK and hsCRP. In
      conclusion, consumption of 500 mL milk attenuated losses in muscle function
      following repeated sprinting and jumping and thus may be a valuable recovery
      intervention for female team-sport athletes following this type of exercise.

PMID- 29462970
TI  - Approaches for Reducing the Risk of Early-Life Iron Deficiency-Induced Brain
      Dysfunction in Children.
AB  - Iron deficiency is the most common micronutrient deficiency in the world. Women
      of reproductive age and young children are particularly vulnerable. Iron
      deficiency in late prenatal and early postnatal periods can lead to long-term
      neurobehavioral deficits, despite iron treatment. This may occur because
      screening and treatment of iron deficiency in children is currently focused on
      detection of anemia and not neurodevelopment. Anemia is the end-stage state of
      iron deficiency. The brain becomes iron deficient before the onset of anemia due
      to prioritization of the available iron to the red blood cells (RBCs) over other
      organs. Brain iron deficiency, independent of anemia, is responsible for the
      adverse neurological effects. Early diagnosis and treatment of impending brain
      dysfunction in the pre-anemic stage is necessary to prevent neurological
      deficits. The currently available hematological indices are not sensitive
      biomarkers of brain iron deficiency and dysfunction. Studies in non-human primate
      models suggest that serum proteomic and metabolomic analyses may be superior for
      this purpose. Maternal iron supplementation, delayed clamping or milking of the
      umbilical cord, and early iron supplementation improve the iron status of at-risk
      infants. Whether these strategies prevent iron deficiency-induced brain
      dysfunction has yet to be determined. The potential for oxidant stress, altered
      gastrointestinal microbiome and other adverse effects associated with iron
      supplementation cautions against indiscriminate iron supplementation of children
      in malaria-endemic regions and iron-sufficient populations.

PMID- 29462971
TI  - Species C Rotaviruses in Children with Diarrhea in India, 2010-2013: A
      Potentially Neglected Cause of Acute Gastroenteritis.
AB  - All over the world, children and adults are severely affected by acute
      gastroenteritis, caused by one of the emerging enteric pathogens, rotavirus C
      (RVC). At present, no extensive surveillance program is running for RVC in India,
      and its prevalence is largely unknown except cases of local outbreaks. Here, we
      intended to detect the presence of RVC in diarrheic children visiting or admitted
      to hospitals in Haldwani (state of Uttarakhand, India), a city located in the
      foothills of the Himalayas. During 2010-2013, we screened 119 samples for RVC by
      an RVC VP6 gene-specific RT-PCR. Of these, 38 (31.93%) were found positive, which
      is higher than the incidence rates reported so far from India. The phylogenetic
      analysis of the derived nucleotide sequences from one of the human RVC (HuRVC)
      isolates, designated as HuRVC/H28/2013/India, showed that the study isolate
      belongs to genotype I2, P2 and E2 for RVC structural genes 6 and 4 (VP6, and VP4)
      and non-structural gene 4 (NSP4), respectively. Furthermore, the VP6 gene of
      HuRVC/H28/2013/India shows the highest similarity to a recently-reported human
      like porcine RVC (PoRVC/ASM140/2013/India, KT932963) from India suggesting
      zoonotic transmission. We also report a full-length NSP4 gene sequence of human
      RVC from India. Under the One-health platforms there is a need to launch combined
      human and animal RVC surveillance programs for a better understanding of the
      epidemiology of RVC infections and for implementing control
      strategies.Reoviridae, possess 11 double-stranded segments of RNA that encode six
      structural viral proteins (VP1, VP2, VP3, VP4, VP6, VP7) and five/six non
      structural proteins (NSP1-NSP5/6) [7]. Based on the antigenic properties of the
      major inner capsid protein (VP6), RVs are subdivided into eight well
      characterized species (A-H) and two putative species viz. I and J [8-10]. Humans
      and other mammalian species are affected by species A, B, C and H rotaviruses and
      birds by species D, F and G, and species E has been reported exclusively in pigs
      [7,8,11-17]. The newly-proposed species I is reported in dogs [18] and cats [19],
      whereas species J is found in bats [10].

PMID- 29462972
TI  - Food-grade Encapsulation Systems for (-)-Epigallocatechin Gallate.
AB  - (-)-Epigallocatechin gallate (EGCG) has attracted significant research interest
      due to its health-promoting effects such as antioxidation, anti-inflammation and
      anti-cancer activities. However, its instability and poor bioavailability have
      largely limited its efficacy and application. Food-grade materials such as
      proteins, carbohydrates and lipids show biodegradability, biocompatibility and
      biofunctionality properties. Food-grade encapsulation systems are usually used to
      improve the bioavailability of EGCG. In the present paper, we provide an overview
      of materials and techniques used in encapsulating EGCG, in which the adsorption
      mechanisms of food-grade systems during in vitro digestion are reviewed.
      Moreover, the potential challenges and future work using food-grade encapsulates
      for delivering EGCG are also discussed.

PMID- 29462973
TI  - The Nordic Prudent Diet Reduces Risk of Cognitive Decline in the Swedish Older
      Adults: A Population-Based Cohort Study.
AB  - Appropriate dietary pattern for preserving cognitive function in northern Europe
      remains unknown. We aimed to identify a Nordic dietary pattern index associated
      with slower cognitive decline compared to the Mediterranean-DASH Intervention for
      Neurodegenerative Delay, Mediterranean Diet, Dietary Approaches to Stop
      Hypertension, and Baltic Sea Diet indices. A total of 2223 dementia-free adults
      aged >=60 were followed for 6 years. Mini-Mental State Examination was
      administrated at baseline and follow-ups. Dietary intake was assessed by 98-item
      food frequency questionnaire, and the Nordic Prudent Dietary Pattern (NPDP) was
      identified. Data were analysed using mixed-effects and parametric survival models
      and receiver operating characteristic curves with adjustment for potential
      confounders. Moderate (beta = 0.139, 95% CI 0.077-0.201) and high adherence (beta
      = 0.238, 95% CI 0.175-0.300) to NPDP were associated with less cognitive decline
      compared to other four indices. High adherence to NPDP was also associated with
      the lowest risk of MMSE decline to <=24 (HR = 0.176, 95% CI 0.080-0.386) and had
      the greatest ability to predict such decline (area under the curve = 0.70).
      Moderate-to-high adherence to the NPDP may predict a better-preserved cognitive
      function among older adults in Nordic countries. Regional dietary habits should
      be considered in developing dietary guidelines for the prevention of cognitive
      impairment and dementia.

PMID- 29462974
TI  - Inadequate Iodine Intake in Population Groups Defined by Age, Life Stage and
      Vegetarian Dietary Practice in a Norwegian Convenience Sample.
AB  - Inadequate iodine intake has been identified in populations considered iodine
      replete for decades. The objective of the current study is to evaluate urinary
      iodine concentration (UIC) and the probability of adequate iodine intake in
      subgroups of the Norwegian population defined by age, life stage and vegetarian
      dietary practice. In a cross-sectional survey, we assessed the probability of
      adequate iodine intake by two 24-h food diaries and UIC from two fasting morning
      spot urine samples in 276 participants. The participants included children (n =
      47), adolescents (n = 46), adults (n = 71), the elderly (n = 23), pregnant women
      (n = 45), ovo-lacto vegetarians (n = 25), and vegans (n = 19). In all
      participants combined, the median (95% CI) UIC was 101 (90, 110) ug/L, median
      (25th, 75th percentile) calculated iodine intake was 112 (77, 175) ug/day and
      median (25th, 75th percentile) estimated usual iodine intake was 101 (75, 150)
      ug/day. According to WHOs criteria for evaluation of median UIC, iodine intake
      was inadequate in the elderly, pregnant women, vegans and non-pregnant women of
      childbearing age. Children had the highest (82%) and vegans the lowest (14%)
      probability of adequate iodine intake according to reported food and supplement
      intakes. This study confirms the need for monitoring iodine intake and status in
      nationally representative study samples in Norway.

PMID- 29462975
TI  - Evaluating the Influence of Chromatic and Luminance Stimuli on SSVEPs from Behind
      the-Ears and Occipital Areas.
AB  - This work presents a study of chromatic and luminance stimuli in low-, medium-,
      and high-frequency stimulation to evoke steady-state visual evoked potential
      (SSVEP) in the behind-the-ears area. Twelve healthy subjects participated in this
      study. The electroencephalogram (EEG) was measured on occipital (Oz) and left and
      right temporal (TP9 and TP10) areas. The SSVEP was evaluated in terms of
      amplitude, signal-to-noise ratio (SNR), and detection accuracy using power
      spectral density analysis (PSDA), canonical correlation analysis (CCA), and
      temporally local multivariate synchronization index (TMSI) methods. It was found
      that stimuli based on suitable color and luminance elicited stronger SSVEP in the
      behind-the-ears area, and that the response of the SSVEP was related to the
      flickering frequency and the color of the stimuli. Thus, green-red stimulus
      elicited the highest SSVEP in medium-frequency range, and green-blue stimulus
      elicited the highest SSVEP in high-frequency range, reaching detection accuracy
      rates higher than 80%. These findings will aid in the development of more
      comfortable, accurate and stable BCIs with electrodes positioned on the behind
      the-ears (hairless) areas.

PMID- 29462977
TI  - Efficiency of Osmotic Dehydration of Apples in Polyols Solutions.
AB  - The present study aimed to evaluate the influence of selected compounds from the
      polyol group, as well as other saccharides, on the osmotic dehydration process of
      apples. The following alternative solutions were examined: erythritol, xylitol,
      maltitol, inulin and oligofructose. Efficiency of the osmotic dehydration process
      was evaluated based on the kinetics of the process, and through comparison of the
      results obtained during the application of a sucrose solution. This innovative
      research utilizes alternative solutions in osmotic pretreatment, which until now,
      have not been commonly used in fruit processing by researchers worldwide. Results
      indicate that erythritol and xylitol show stronger or similar efficiency to
      sucrose; however, the use of inulin, as well as oligofructose, was not
      satisfactory due to the insufficient, small osmotic driving forces of the
      process, and the low values of mass transfer parameters.

PMID- 29462976
TI  - A Theoretical and Empirical Linkage between Road Accidents and Binge Eating
      Behaviors in Adolescence.
AB  - This study aimed at identifying specific clusters of maladaptive emotional
      behavioral symptoms in adolescent victims of motorbike collisions considering
      their scores on alexithymia and impulsivity in addition to examining the
      prevalence of clinical binge eating behaviors (respectively through the Youth
      Self-Report (YSR), Toronto Alexithymia Scale-20 (TAS-20), Barratt Impulsiveness
      Scale-11 (BIS-11), and Binge Eating Scale (BES)). Emotional-behavioral profiles,
      difficulties in identifying and describing feelings, impulsivity, and binge
      eating behaviors have been assessed in 159 adolescents addressing emergency
      departments following motorbike collisions. Our results showed a cluster of
      adolescents with clinical binge eating behaviors, high rates of motorbike
      accidents, and high levels of internalizing and externalizing problems,
      alexithymia, and impulsivity (23.3% of the sample); a second cluster of
      adolescents with clinical binge eating behaviors, a moderate number of
      collisions, and moderate levels of emotional and behavioral problems on the above
      four dimensions (25.8% of the sample); and a third cluster of youth without
      clinical binge eating behaviors, with a moderate number of accidents, and with
      low scores on the four dimensions (50.9% of the sample). Adolescents of Cluster 1
      showed a higher likelihood to be involved in motorbike collisions than the youth
      in Clusters 2 and 3 (p < 0.0001). We suggest that adolescents' motor collisions
      could be associated with their difficulties in emotion regulation and with their
      impaired psychological profiles, which could also underpin their disordered
      eating. The identification of specific clusters of psychopathological symptoms
      among this population could be useful for the construction of prevention and
      intervention programs aimed at reducing motor collision recidivism and
      alleviating co-occurring psychopathologies.

PMID- 29462978
TI  - Impact of Western and Mediterranean Diets and Vitamin D on Muscle Fibers of
      Sedentary Rats.
AB  - BACKGROUND: The metabolic syndrome is associated with sarcopenia. Decreased serum
      levels of Vitamin D (VitD) and insulin-like growth factor (IGF)-1 and their
      mutual relationship were also reported. We aimed to evaluate whether different
      dietary profiles, containing or not VitD, may exert different effects on muscle
      molecular morphology. METHODS: Twenty-eight male rats were fed for 10 weeks in
      order to detect early defects induced by different dietary regimens: regular diet
      (R); regular diet with vitamin D supplementation (R-DS) and regular diet with
      vitamin D restriction (R-DR); high-fat butter-based diets (HFB-DS and HFB-DR)
      with 41% energy from fat; high-fat extra-virgin olive oil-based diets (HFEVO-DS
      and HFEVO-DR) with 41% energy from fat. IL-1beta, insulin-like growth factor
      (IGF)1, Dickkopf-1 (DKK-1), and VitD-receptor (VDR) expressions were evaluated by
      immunohistochemistry. Muscle fiber perimeter was measured by histology and
      morphometric analysis. RESULTS: The muscle fibers of the HEVO-DS rats were
      hypertrophic, comparable to those of the R-DS rats. An inverse correlation
      existed between the dietary fat content and the perimeter of the muscle fibers (p
      < 0.01). In the HFB-DR rats, the muscle fibers appeared hypotrophic with an
      increase of IL-1beta and a dramatic decrease of IGF-1 expression. CONCLUSIONS:
      High-fat western diet could impair muscle metabolism and lay the ground for
      subsequent muscle damage. VitD associated with a Mediterranean diet showed
      trophic action on the muscle fibers.

PMID- 29462979
TI  - Mindfulness Is Associated with the Metabolic Syndrome among Individuals with a
      Depressive Symptomatology.
AB  - The Metabolic Syndrome (MetS) is a major public health burden. Dispositional
      mindfulness has recently been associated with eating disorders, being overweight,
      and could therefore be associated with the MetS. We aimed to examine in a cross
      sectional design the relationship between mindfulness, the MetS, and its risk
      factors in a large sample of the adult general population and the influence of
      depressive symptomatology on this association. Adults participating in the
      NutriNet-Sante study who had completed the Five Facets Mindfulness Questionnaire
      and attended a clinical and biological examination were available for inclusion.
      Multivariable logistic regression models adjusted for socio-demographic and
      lifestyle factors were performed. A total of 17,490 individuals were included.
      Among individuals with a depressive symptomatology, those with higher mindfulness
      were less likely to have a MetS (OR: 0.73, 95% CI: 0.57-0.93), a high waist
      circumference, a low HDL-cholesterol level and an elevated fasting blood glucose
      level (all p <0.05). In those without depressive symptomatology, individuals with
      higher mindfulness were less likely to have a high waist circumference (p <0.01).
      In conclusion, higher mindfulness was associated with lower odds of developing a
      MetS only among individuals with a depressive symptomatology.

PMID- 29462980
TI  - Characterization of the Venom of C. d. cumanesis of Colombia: Proteomic Analysis
      and Antivenomic Study.
AB  - The Colombian rattlesnake Crotalus durissus cumanensis is distributed in three
      geographic zones of the country: the Atlantic Coast, the upper valley of the
      Magdalena River, and the eastern plains of the Colombian Orinoquia. Its venom
      induces neurological symptoms, such as eyelid ptosis, myasthenic facies, and
      paralysis of the respiratory muscles, which can lead to death. Identification and
      analysis of C. d. cumanensis showed nine groups of proteins responsible for the
      neurotoxic effect, of which the crotoxin complex was the most abundant (64.71%).
      Immunorecognition tests of C. d. cumanensis showed that the use of a commercial
      antivenom manufactured in Mexico resulted in immunoreactivity.

PMID- 29462981
TI  - Sensor-Based Assessment of Soil Salinity during the First Years of Transition
      from Flood to Sprinkler Irrigation.
AB  - A key issue for agriculture in irrigated arid lands is the control of soil
      salinity, and this is one of the goals for irrigated districts when changing from
      flood to sprinkling irrigation. We combined soil sampling, proximal
      electromagnetic induction, and satellite data to appraise how soil salinity and
      its distribution along a previously flood-irrigated field evolved after its
      transformation to sprinkling. We also show that the relationship between NDVI
      (normalized difference vegetation index) and ECe (electrical conductivity of the
      soil saturation extracts) mimics the production function between yield and soil
      salinity. Under sprinkling, the field had a double crop of barley and then
      sunflower in 2009 and 2011. In both years, about 50% of the soil of the entire
      studied field-45 ha-had ECe < 8 dS m-1, i.e., allowing barley cultivation, while
      the percent of surface having ECe >= 16 dS m-1 increased from 8.4% in 2009 to
      13.7% in 2011. Our methodology may help monitor the soil salinity oscillations
      associated with irrigation management. After quantifying and mapping the soil
      salinity in 2009 and 2011, we show that barley was stunted in places of the field
      where salinity was higher. Additionally, the areas of salinity persisted after
      the subsequent alfalfa cropping in 2013. Application of differential doses of
      water to the saline patches is a viable method to optimize irrigation water
      distribution and lessen soil salinity in sprinkler-irrigated agriculture.

PMID- 29462982
TI  - Fusarium graminearum in Stored Wheat: Use of CO2 Production to Quantify Dry
      Matter Losses and Relate This to Relative Risks of Zearalenone Contamination
      under Interacting Environmental Conditions.
AB  - Zearalenone (ZEN) contamination from Fusarium graminearum colonization is
      particularly important in food and feed wheat, especially during post-harvest
      storage with legislative limits for both food and feed grain. Indicators of the
      relative risk from exceeding these limits would be useful. We examined the effect
      of different water activities (aw; 0.95-0.90) and temperature (10-25  degrees C)
      in naturally contaminated and irradiated wheat grain, both inoculated with F.
      graminearum and stored for 15 days on (a) respiration rate; (b) dry matter losses
      (DML); (c) ZEN production and (d) relationship between DML and ZEN contamination
      relative to the EU legislative limits. Gas Chromatography was used to measure the
      temporal respiration rates and the total accumulated CO2 production. There was an
      increase in temporal CO2 production rates in wetter and warmer conditions in all
      treatments, with the highest respiration in the 25  degrees C * 0.95 aw
      treatments + F. graminearum inoculation. This was reflected in the total
      accumulated CO2 in the treatments. The maximum DMLs were in the 0.95 aw/20-25 
      degrees C treatments and at 10  degrees C/0.95 aw. The DMLs were modelled to
      produce contour maps of the environmental conditions resulting in maximum/minimum
      losses. Contamination with ZEN/ZEN-related compounds were quantified. Maximum
      production was at 25  degrees C/0.95-0.93 aw and 20  degrees C/0.95 aw. ZEN
      contamination levels plotted against DMLs for all the treatments showed that at
      ca <1.0% DML, there was a low risk of ZEN contamination exceeding EU legislative
      limits, while at >1.0% DML, the risk was high. This type of data is important in
      building a database for the development of a post-harvest decision support system
      for relative risks of different mycotoxins.

PMID- 29462983
TI  - A Survey on West Nile and Usutu Viruses in Horses and Birds in Poland.
AB  - West Nile virus (WNV) and Usutu virus (USUV) are members of the family
      Flaviviridae which, natural life cycles involve mosquito-bird-mosquito
      transmission. Both represent emerging viruses in Europe with potential to cause
      neuroinvasive disease in humans. This study investigates the seroprevalence of
      serum neutralizing antibodies to WNV and to USUV in birds and in horses in
      Poland. Antibodies against WNV and USUV were detected in 5 (35.7%) and in 1
      (7.14%) of 14 birds and in 62 (15.08%) and in 115 (27.98%) of 411 horses,
      respectively. Twenty-one WNV serologically positive horses (33.87%) and 67 USUV
      serologically positive horses (58.26%) did not travel outside Polish borders.
      Given the high abundance of potentially competent mosquito species in Poland,
      high populations of horses and different bird species, our findings highlight
      implementation of active control programs, including monitoring of geographic
      spread and dynamics of WNV and USUV transmission in both primary and accidental
      hosts. It is also important to improve public health awareness about the disease
      these viruses may cause.

PMID- 29462984
TI  - Mathematical Modelling of Nitric Oxide/Cyclic GMP/Cyclic AMP Signalling in
      Platelets.
AB  - Platelet activation contributes to normal haemostasis but also to pathologic
      conditions like stroke and cardiac infarction. Signalling by cGMP and cAMP
      inhibit platelet activation and are therefore attractive targets for thrombosis
      prevention. However, extensive cross-talk between the cGMP and cAMP signalling
      pathways in multiple tissues complicates the selective targeting of their
      activities. We have used mathematical modelling based on experimental data from
      the literature to quantify the steady state behaviour of nitric oxide
      (NO)/cGMP/cAMP signalling in platelets. The analysis provides an assessment of NO
      induced cGMP synthesis and PKG activation as well as cGMP-mediated cAMP and PKA
      activation though modulation of phosphodiesterase (PDE2 and 3) activities. Both
      one- and two-compartment models of platelet cyclic nucleotide signalling are
      presented. The models provide new insight for understanding how NO signalling to
      cGMP and indirectly cAMP, can inhibit platelet shape-change, the initial step of
      platelet activation. Only the two-compartment models could account for the
      experimental observation that NO-mediated PKA activation can occur when the bulk
      platelet cAMP level is unchanged. The models revealed also a potential for
      hierarchical interplay between the different platelet phosphodiesterases.
      Specifically, the models predict, unexpectedly, a strong effect of
      pharmacological inhibitors of cGMP-specific PDE5 on the cGMP/cAMP cross-talk.
      This may explain the successful use of weak PDE5-inhibitors, such as
      dipyridamole, in anti-platelet therapy. In conclusion, increased NO signalling or
      PDE5 inhibition are attractive ways of increasing cGMP-cAMP cross-talk
      selectively in platelets.

PMID- 29462985
TI  - Melatonin Regulates the Synthesis of Steroid Hormones on Male Reproduction: A
      Review.
AB  - Melatonin is a ubiquitous molecule and exhibits different effects in long-day and
      short-day breeding animals. Testosterone, the main resource of androgens in the
      testis, is produced by Leydig cells but regulated mainly by cytokine secreted by
      Sertoli cells. Melatonin acts as a local modulator of the endocrine activity in
      Leydig cells. In Sertoli cells, melatonin influences cellular proliferation and
      energy metabolism and, consequently, can regulate steroidogenesis. These suggest
      melatonin as a key player in the regulation of steroidogenesis. However, the
      melatonin-induced regulation of steroid hormones may differ among species, and
      the literature data indicate that melatonin has important effects on
      steroidogenesis and male reproduction.

PMID- 29462986
TI  - I Can Stand Learning: A Controlled Pilot Intervention Study on the Effects of
      Increased Standing Time on Cognitive Function in Primary School Children.
AB  - Sedentarism is considered an independent cardiovascular risk factor. Thus, the
      present study investigated the effects of employing standing desks in classrooms
      on cognitive function. The intervention class (IG; n = 19) was supplied with
      standing desks and balance pads for 11 weeks. The control class (CG; n = 19)
      received lessons as usual. Standing time was assessed objectively
      (accelerometers) and subjectively (self-report sheets, external classroom
      observers). The impact of standing on the digit span task and Eriksen flanker
      task was analysed. The standing time of the IG was higher during the school day
      in comparison to the CG (lesson: p = 0.004; break: p = 0.003). The intra-class
      correlation coefficient between self-reports and external observation was high
      (ICC = 0.94). The IG improved slightly on the Digit Span Task compared to CG.
      Employing standing desks for at least 1 h per school day serves as a feasible and
      effective opportunity to improve cognitive function.

PMID- 29462987
TI  - Mechanisms of Phosphorus Removal by Recycled Crushed Concrete.
AB  - Due to urbanisation, there are large amounts of waste concrete, particularly in
      rapidly industrialising countries. Currently, demolished concrete is mainly
      recycled as aggregate for reconstruction. This study has shown that larger sizes
      (2-5 mm) of recycled concrete aggregate (RCA) removed more than 90% of P from
      effluent when at pH 5. Analysis of the data, using equilibrium models, indicated
      a best fit with the Langmuir which predicated an adsorption capacity of 6.88
      mg/g. Kinetic analysis indicated the equilibrium adsorption time was 12 h, with
      pseudo second-order as the best fit. The thermal dynamic tests showed that the
      adsorption was spontaneous and, together with the evidence from the sequential
      extraction and desorption experiments, indicated the initial mechanism was
      physical attraction to the surface followed by chemical reactions which prevented
      re-release. These results suggested that RCA could be used for both wastewater
      treatment and P recovery.

PMID- 29462989
TI  - Memristic Characteristics from Bistable to Tristable Memory with Controllable
      Charge Trap Carbon Nanotubes.
AB  - The incorporation of the one-dimensional carbon nanomaterial carbon nanotubes
      (CNTs) in poly(methyl methacrylate) (PMMA) was found to successfully develop a
      resistive switching. It implements memristic characteristics which shift from
      bistable to tristable memory. The localized current pathways in the organic
      nanocomposite layers for each intermediate resistive state (IRS) are attributed
      to the trapping mechanism consistent with the fluorescent measurements. Multi-bit
      organic memories have attracted considerable interest, which provide an effective
      way to increase the memory density per unit cell area. This study will be useful
      for the development and tuning of multi-bit storable organic nanocomposite memory
      device systems.

PMID- 29462988
TI  - A pi-Halogen Bond of Dibenzofuranones with the Gatekeeper Phe113 in Human Protein
      Kinase CK2 Leads to Potent Tight Binding Inhibitors.
AB  - Human protein kinase CK2 is an emerging target for neoplastic diseases. Potent
      lead structures for human CK2 inhibitors are derived from dibenzofuranones. Two
      new derivatives, 7,9-dichloro-1,2-dihydro-8-hydroxy-4-[(4-methoxyphenylamino)
      methylene]dibenzo[b,d]furan-3(2H)-one (4a) and (E)-1,3-dichloro-6-[(4
      methoxyphenylimino)-methyl]dibenzo[b,d]furan-2,7-diol (5) were tested for
      inhibition of CK2 and induction of apoptosis in LNCaP cells. Both turned out to
      be tight binding inhibitors, with IC50 values of 7 nM (4a) and 5 nM (5) and an
      apparent Ki value of 0.4 nM for both. Compounds 4a and 5 reduced cellular CK2
      activity, indicating cell permeability. Cell viability was substantially impaired
      in LNCaP cells, as well as apoptosis was induced, which was not appearing in non
      neoplastic ARPE-19 cells. Co-crystallization of 4a and 5 revealed an unexpected
      pi-halogen bond of the chloro substituent at C9 with the gatekeeper amino acid
      Phe113, leading to an inverted binding mode in comparison to parent compound 4b,
      with the Cl at C6 instead, which was co-crystallized as a control. This indicates
      that the position of the chloro substituent on ring A of the dibenzofuran
      scaffold is responsible for an inversion of the binding mode that enhances
      potency.

PMID- 29462990
TI  - Exploration of Rice Husk Compost as an Alternate Organic Manure to Enhance the
      Productivity of Blackgram in Typic Haplustalf and Typic Rhodustalf.
AB  - The present study was aimed at using cellulolytic bacterium Enhydrobacter and
      fungi Aspergillus sp. for preparing compost from rice husk (RH). Further, the
      prepared compost was tested for their effect on blackgram growth promotion along
      with different levels of recommended dose of fertilizer (RDF) in black soil
      (typic Haplustalf) and red soil (typic Rhodustalf) soil. The results revealed
      that, inoculation with lignocellulolytic fungus (LCF) Aspergillus sp. @ 2% was
      considered as the most efficient method of composting within a short period.
      Characterization of composted rice husk (CRH) was examined through scanning
      electron microscope (SEM) for identifying significant structural changes. At the
      end of composting, N, P and K content increased with decrease in CO2 evolution,
      C:N and C:P ratios. In comparison to inorganic fertilization, an increase in
      grain yield of 16% in typic Haplustalf and 17% in typic Rhodustalf soil over 100%
      RDF was obtained from the integrated application of CRH@ 5 t ha-1 with 50% RDF
      and biofertilizers. The crude protein content was maximum with the combined
      application of CRH, 50% RDF and biofertilizers of 20% and 21% in typic Haplustalf
      and typic Rhodustalf soils, respectively. Nutrient rich CRH has proved its
      efficiency on crop growth and soil fertility.

PMID- 29462991
TI  - Functionalized Asymmetric Bola-Type Amphiphiles for Efficient Gene and Drug
      Delivery.
AB  - The studies of bolaamphiphile-based nanoparticles as delivery vectors are still
      rudimentary and under development. In this study, several asymmetric
      bolaamphiphiles containing lysine and another moiety with special functions, such
      as pH-sensitive or cell-targeting property, were designed and synthesized. The
      potentials of these bolaamphiphile-based nanoparticles as versatile vectors for
      both nucleic acids and chemical drugs were studied. With the presence of 1,2
      dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), these amphiphiles could be
      prepared into bolasomes, which showed good DNA binding ability and could condense
      plasmid DNA into nanoparticles with appropriate size and surface potential. Lys
      His, which has a pH-sensitive histidine on one head, exhibited higher
      transfection efficiency than the symmetric counterpart and comparable efficiency
      to commercially available transfection reagent. Mechanism studies confirmed that
      the bolaplexes formed from Lys-His might induce the highest cellular uptake and
      the best endosomal escape ability. On the other hand, these bolaamphiphiles also
      exhibited good drug loading ability. The self-assembly vesicles could efficiently
      encapsulate the hydrophobic anti-cancer drug doxorubicin (DOX) in aqueous
      solution with high drug loading content and encapsulation efficiency. Confocal
      laser scanning microscopy (CLSM) experiment and cell viability assay exhibited a
      controlled release of the drug with the assistance of bolasomes. It was shown
      that such bolaamphiphiles have great potential as nano-vectors for both drug and
      gene or their co-delivery.

PMID- 29462992
TI  - New Bacterial Phytase through Metagenomic Prospection.
AB  - Alkaline phytases from uncultured microorganisms, which hydrolyze phytate to less
      phosphorylated myo-inositols and inorganic phosphate, have great potential as
      additives in agricultural industry. The development of metagenomics has stemmed
      from the ineluctable evidence that as-yet-uncultured microorganisms represent the
      vast majority of organisms in most environments on earth. In this study, a gene
      encoding a phytase was cloned from red rice crop residues and castor bean cake
      using a metagenomics strategy. The amino acid identity between this gene and its
      closest published counterparts is lower than 60%. The phytase was named PhyRC001
      and was biochemically characterized. This recombinant protein showed activity on
      sodium phytate, indicating that PhyRC001 is a hydrolase enzyme. The enzymatic
      activity was optimal at a pH of 7.0 and at a temperature of 35  degrees C. beta
      propeller phytases possess great potential as feed additives because they are the
      only type of phytase with high activity at neutral pH. Therefore, to explore and
      exploit the underlying mechanism for beta-propeller phytase functions could be of
      great benefit to biotechnology.

PMID- 29462995
TI  - Research on the Additional Secondary Phase Factor for Automatic Identification
      System Signals Transmitted over a Rough Sea Surface.
AB  - This paper investigates the Additional Secondary Phase Factor (ASF)
      characteristics of Automatic Identification System (AIS) signals spreading over a
      rough sea surface. According to the change of the ASFs for AIS signals in
      different signal form, the influences of the different propagation conditions on
      the ASFs are analyzed. The expression, numerical calculation, and simulation
      analysis of the ASFs of AIS signal are performed in the rough sea surface. The
      results contribute to the high-accuracy propagation delay measurement of AIS
      signals spreading over the rough sea surface as, well as providing a reference
      for reliable communication link design in marine engineering for Very High
      Frequency (VHF) signals.

PMID- 29462993
TI  - The Biased G-Protein-Coupled Receptor Agonism Bridges the Gap between the Insulin
      Receptor and the Metabolic Syndrome.
AB  - Insulin signaling, as mediated through the insulin receptor (IR), plays a
      critical role in metabolism. Aberrations in this signaling cascade lead to
      several pathologies, the majority of which are classified under the umbrella term
      "metabolic syndrome". Although many of these pathologies are associated with
      insulin resistance, the exact mechanisms are not well understood. One area of
      current interest is the possibility of G-protein-coupled receptors (GPCRs)
      influencing or regulating IR signaling. This concept is particularly significant,
      because GPCRs have been shown to participate in cross-talk with the IR. More
      importantly, GPCR signaling has also been shown to preferentially regulate
      specific downstream signaling targets through GPCR agonist bias. A novel study
      recently demonstrated that this GPCR-biased agonism influences the activity of
      the IR without the presence of insulin. Although GPCR-IR cross-talk has
      previously been established, the notion that GPCRs can regulate the activation of
      the IR is particularly significant in relation to metabolic syndrome and other
      pathologies that develop as a result of alterations in IR signaling. As such, we
      aim to provide an overview of the physiological and pathophysiological roles of
      the IR within metabolic syndrome and its related pathologies, including
      cardiovascular health, gut microflora composition, gastrointestinal tract
      functioning, polycystic ovarian syndrome, pancreatic cancer, and
      neurodegenerative disorders. Furthermore, we propose that the GPCR-biased agonism
      may perhaps mediate some of the downstream signaling effects that further
      exacerbate these diseases for which the mechanisms are currently not well
      understood.

PMID- 29462994
TI  - Improving Behavioral Support for Smoking Cessation in Pregnancy: What Are the
      Barriers to Stopping and Which Behavior Change Techniques Can Influence These?
      Application of Theoretical Domains Framework.
AB  - Behavioral support interventions are used to help pregnant smokers stop; however,
      of those tested, few are proven effective. Systematic research developing
      effective pregnancy-specific behavior change techniques (BCTs) is ongoing. This
      paper reports contributory work identifying potentially-effective BCTs relative
      to known important barriers and facilitators (B&Fs) to smoking cessation in
      pregnancy; to detect priority areas for BCTs development. A Nominal Group
      Technique with cessation experts (n = 12) elicited an expert consensus on B&Fs
      most influencing women's smoking cessation and those most modifiable through
      behavioral support. Effective cessation interventions in randomized trials from a
      recent Cochrane review were coded into component BCTs using existing taxonomies.
      B&Fs were categorized using Theoretical Domains Framework (TDF) domains.
      Matrices, mapping BCT taxonomies against TDF domains, were consulted to
      investigate the extent to which BCTs in existing interventions target key B&Fs.
      Experts ranked "smoking a social norm" and "quitting not a priority" as most
      important barriers and "desire to protect baby" an important facilitator to
      quitting. From 14 trials, 23 potentially-effective BCTs were identified (e.g.,
      information about consequences). Most B&Fs fell into "Social Influences",
      "Knowledge", "Emotions" and "Intentions" TDF domains; few potentially-effective
      BCTs mapped onto every TDF domain. B&Fs identified by experts as important to
      cessation, are not sufficiently targeted by BCT's currently within interventions
      for smoking cessation in pregnancy.

PMID- 29462996
TI  - Nanocantilevers with Adjustable Static Deflection and Significantly Tunable
      Spectrum Resonant Frequencies for Applications in Nanomechanical Mass Sensors.
AB  - Nanocantilevers have become key components of nanomechanical sensors that exploit
      changes in their resonant frequencies or static deflection in response to the
      environment. It is necessary that they can operate at a given, but adjustable,
      resonant frequency and/or static deflection ranges. Here we propose a new class
      of nanocantilevers with a significantly tunable spectrum of the resonant
      frequencies and changeable static deflection utilizing the unique properties of a
      phase-transforming NiTi film sputtered on the usual nanotechnology cantilever
      materials. The reversible frequency tuning and the adjustable static deflection
      are obtained by intentionally changing the Young's modulus and the interlayer
      stress of the NiTi film during its phase transformation, while the usual
      cantilever elastic materials guarantee a high frequency actuation (up to tens of
      MHz). By incorporating the NiTi phase transformation characteristic into the
      classical continuum mechanics theory we present theoretical models that account
      for the nanocantilever frequency shift and variation in static deflection caused
      by a phase transformation of NiTi film. Due to the practical importance in
      nanomechanical sensors, we carry out a complete theoretical analysis and evaluate
      the impact of NiTi film on the cantilever Young's modulus, static deflection, and
      the resonant frequencies. Moreover, the importance of proposed NiTi
      nanocantilever is illustrated on the nanomechanical based mass sensors. Our
      findings will be of value in the development of advanced nanotechnology sensors
      with intentionally-changeable physical and mechanical properties.

PMID- 29462997
TI  - Effect of a Fibroin Enzymatic Hydrolysate on Memory Improvement: A Placebo
      Controlled, Double-Blind Study.
AB  - The consumption of a specifically prepared silk fibroin protein enzymatic
      hydrolysate (FPEH) has been reported to improve cognitive function in healthy
      humans. The objective of the current study is to evaluate the dose-dependent
      effects of the FPEH on memory. Healthy adults with an average age of
      approximately 55 years were administered doses of 0, 280, 400 and 600 mg of FPEH
      per day in two divided doses for 3 weeks. The Rey-Kim Auditory Verbal Learning
      Test and the Rey-Kim Complex Figure Test of the Rey-Kim Memory Test were used to
      evaluate memory at baseline and after 3 weeks. The scores for each test were
      combined into the memory quotient score (MQ). Learning gradient, memory
      maintenance, retrieval efficacy, and drawing/recall scores were also compared.
      After 3 weeks of FPEH, dose-dependent increases were observed for the MQ, the
      learning gradient, the numbers of words remembered, the retrieval efficiency, and
      drawing/recall. The optimal dose for FPEH was 400 or 600 mg, depending on the end
      point measured. No adverse effects were reported. FPEH significantly improved
      measurements of memory in healthy adults by 3 weeks at doses over 280 mg daily,
      with an apparent plateau effect at 400-600 mg daily.

PMID- 29462999
TI  - An On-Site Simultaneous Semi-quantification of Aflatoxin B1, Zearalenone, and T-2
      Toxin in Maize- and Cereal-based Feed via Multicolor Immunochromatographic Assay.
AB  - Multiple-mycotoxin contamination has been frequently found in the agro-food
      monitoring due to the coexistence of fungi. However, many determination methods
      focused on a single mycotoxin, highlighting the demand for on-site determination
      of multiple mycotoxins in a single run. We develop a multicolor-based
      immunochromatographic strip (ICS) for simultaneous determination of aflatoxin B1
      (AFB1), zearalenone (ZEN) and T-2 toxin in maize- and cereal-based animal feeds.
      The nanoparticles with different colors are conjugated with three monoclonal
      antibodies, which serve as the immunoassay probes. The decrease in color
      intensity is observed by the naked eyes, providing simultaneous quantification of
      three mycotoxins. The visible limits of detection for AFB1, ZEN and T-2 are
      estimated to be 0.5, 2, and 30 ng/mL, respectively. The cut-off values are 1, 10,
      and 50 ng/mL, respectively. Considerable specificity and stability are found
      using real samples. The results are in excellent agreement with those from high
      performance liquid chromatography/tandem mass spectrometry. The multi-color ICS
      boasts sensitive and rapid visual differentiation and simultaneous semi
      quantification of aflatoxin B1, zearalenone and T-2 toxin in maize- and cereal
      based feed samples within 20 min.

PMID- 29462998
TI  - AOX1-Subfamily Gene Members in Olea europaea cv. "Galega Vulgar"-Gene
      Characterization and Expression of Transcripts during IBA-Induced in Vitro
      Adventitious Rooting.
AB  - Propagation of some Olea europaea L. cultivars is strongly limited due to
      recalcitrant behavior in adventitious root formation by semi-hardwood cuttings.
      One example is the cultivar "Galega vulgar". The formation of adventitious roots
      is considered a morphological response to stress. Alternative oxidase (AOX) is
      the terminal oxidase of the alternative pathway of the plant mitochondrial
      electron transport chain. This enzyme is well known to be induced in response to
      several biotic and abiotic stress situations. This work aimed to characterize the
      alternative oxidase 1 (AOX1)-subfamily in olive and to analyze the expression of
      transcripts during the indole-3-butyric acid (IBA)-induced in vitro adventitious
      rooting (AR) process. OeAOX1a (acc. no. MF410318) and OeAOX1d (acc. no. MF410319)
      were identified, as well as different transcript variants for both genes which
      resulted from alternative polyadenylation events. A correlation between
      transcript accumulation of both OeAOX1a and OeAOX1d transcripts and the three
      distinct phases (induction, initiation, and expression) of the AR process in
      olive was observed. Olive AOX1 genes seem to be associated with the induction and
      development of adventitious roots in IBA-treated explants. A better understanding
      of the molecular mechanisms underlying the stimulus needed for the induction of
      adventitious roots may help to develop more targeted and effective rooting
      induction protocols in order to improve the rooting ability of difficult-to-root
      cultivars.

PMID- 29463000
TI  - AWRK6, A Synthetic Cationic Peptide Derived from Antimicrobial Peptide Dybowskin
      2CDYa, Inhibits Lipopolysaccharide-Induced Inflammatory Response.
AB  - Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative
      bacteria and produce strong inflammatory responses in animals. Most antibiotics
      have shown little clinical anti-endotoxin activity while some antimicrobial
      peptides have proved to be effective in blocking LPS. Here, the anti-LPS activity
      of the synthetic peptide AWRK6, which is derived from antimicrobial peptide
      dybowskin-2CDYa, has been investigated in vitro and in vivo. The positively
      charged alpha-helical AWRK6 was found to be effective in blocking the binding of
      LBP (LPS binding protein) with LPS in vitro using ELISA. In a murine endotoxemia
      model, AWRK6 offered satisfactory protection efficiency against endotoxemia
      death, and the serum levels of LPS, IL-1beta, IL-6, and TNF-alpha were found to
      be attenuated using ELISA. Further, histopathological analysis suggested that
      AWRK6 could improve the healing of liver and lung injury in endotoxemia mice. The
      results of real-time PCR and Western blotting showed that AWRK6 significantly
      reversed LPS-induced TLR4 overexpression and IkappaB depression, as well as the
      enhanced IkappaB phosphorylation. Additionally, AWRK6 did not produce any
      significant toxicity in vivo and in vitro. In summary, AWRK6 showed efficacious
      protection from LPS challenges in vivo and in vitro, by blocking LPS binding to
      LBP, without obvious toxicity, providing a promising strategy against LPS-induced
      inflammatory responses.

PMID- 29463001
TI  - The Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium erinaceus
      Mycelium Ameliorate Alzheimer's Disease-Related Pathologies in APP/PS1 Transgenic
      Mice.
AB  - Hericium erinaceus was used in traditional Chinese medicine for physiologically
      beneficial medicines. Recently, it has become a candidate in causing positive
      brain health-related activities. We previously reported that Hericium erinaceus
      mycelium ameliorates Alzheimer's disease (AD)-related pathologies. To reveal the
      role of the cyanthin diterpenoid and sesterterpene constituents on this effects,
      erinacine A and S were isolated and their effects on attenuating AD-related
      pathology in APPswe/PS1dE9 transgenic mice were investigated. A 30 day short-term
      administration of erinacine A and S were performed to explore the effect of each
      erinacine on AD-related pathology including amyloid beta production and
      degradation, plaque formation, plaque growth, glial activation and neurogenesis
      deterioration. Our results indicated the benefit effects of both erinacine A and
      S in cerebrum of APPswe/PS1dE9 mice, including: (1) attenuating cerebral plaque
      loading by inhibiting plaque growth; (2) diminishing the activation of glial
      cells; (3) raising the level of insulin degrading enzyme; and (4) promoting
      hippocampal neurogenesis. Moreover, erinacine A reduced the level of insoluble
      amyloid beta and C-terminal fragment of amyloid precursor protein which was not
      mediated by erinacine S. We further performed a long term administration of
      erinacine A and found that erinacine A recovered the impairment in the tasks
      including burrowing, nesting, and Morris water maze. Our data pointed out that
      although both erinacine A and S reduce AD pathology via reducing amyloid
      deposition and promoting neurogenesis, erinacine A can also inhibit amyloid beta
      production and is worth to be further developed for AD therapeutic use.

PMID- 29463002
TI  - Inhibitory Effect of Purpurogallin on Osteoclast Differentiation in Vitro through
      the Downregulation of c-Fos and NFATc1.
AB  - Purpurogallin, a benzotropolone-containing natural compound, has been reported to
      exhibit numerous biological and pharmacological functions, such as antioxidant,
      anticancer, and anti-inflammatory effects. In this study, we enzymatically
      synthesized purpurogallin from pyrogallol and investigated its role in receptor
      activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclastogenesis.
      Purpurogallin attenuated the formation of multinucleated tartrate-resistant acid
      phosphatase (TRAP)-positive osteoclasts from bone marrow macrophages (BMMs)
      without causing cytotoxicity, and suppressed upregulation of osteoclast-specific
      markers, including TRAP (Acp5), cathepsin K (Ctsk), and dendritic cell-specific
      transmembrane protein (Dcstamp). However, purpurogallin did not affect the bone
      resorbing function of mature osteoclasts evident by the resorption pit assay.
      Activation of mitogen-activated protein kinases, Akt and IkB pathways in RANK
      signaling were not altered by purpurogallin, whereas the expression of c-Fos and
      NFATc1, key transcriptional regulators in osteoclastogenesis, was dramatically
      inhibited by purpurogallin. Purpurogallin also significantly reduced the
      expression level of B lymphocyte-induced maturation protein-1 (Blimp1) gene
      (Prdm1). Further, downregulation of Blimp1 led to forced expression of anti
      osteoclastogenic genes, including interferon regulatory factor-8 (Irf8) and B
      cell lymphoma 6 (Bcl6) genes. Taken together, our data suggested that
      purpurogallin inhibits osteoclast differentiation via downregulation of c-Fos and
      NFATc1.

PMID- 29463004
TI  - Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer.
AB  - Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an
      advanced incurable stage. Despite improvements in diagnostic modalities and
      management strategies, including surgery and chemotherapies, the outcome of
      pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging
      tool for pancreas cancer. For decades, resected pancreas cancer and other cancer
      specimens have been used to identify tissue biomarkers or genomics for precision
      therapy; however, only 20% of patients undergo surgery, and thus, this framework
      is not useful for unresectable pancreas cancer. With advancements in needle
      technologies, tumor specimens can be obtained at the time of tissue diagnosis.
      Tumor tissue can be used for development of personalized cancer treatment, such
      as performing whole exome sequencing and global genomic profiling of pancreas
      cancer, development of tissue biomarkers, and targeted mutational assays for
      precise chemotherapy treatment. In this review, we discuss the recent advances in
      tissue acquisition of pancreas cancer.

PMID- 29463003
TI  - The miRNA Mirage: How Close Are We to Finding a Non-Invasive Diagnostic Biomarker
      in Endometriosis? A Systematic Review.
AB  - BACKGROUND: Endometriosis is a common disorder of the reproductive age group,
      characterised by the presence of ectopic endometrial tissue. The disease not only
      causes enormous suffering to the affected women, but also brings a tremendous
      medical and economic burden to bear on society. There is a long lag phase between
      the onset and diagnosis of the disease, mainly due to its non-specific symptoms
      and the lack of a non-invasive test. Endometriosis can only be diagnosed
      invasively by laparoscopy. A specific, non-invasive test to diagnose
      endometriosis is an unmet clinical need. The recent discovery of microRNAs
      (miRNAs) as modulators of gene expression, and their stability and specificity,
      make them an attractive candidate biomarker. Various studies on miRNAs in
      endometriosis have identified their cardinal role in the pathogenesis of the
      disease, and have proposed them as potential biomarkers in endometriosis.
      Rationale/Objectives: The aims of this review were to study the role of
      circulatory miRNAs in endometriosis, and bring to light whether circulatory
      miRNAs could be potential non-invasive biomarkers to diagnose the disease. SEARCH
      METHODS: Three databases, PubMed, EMBASE, and BIOSIS were searched, using a
      combination of Mesh or Emtree headings and free-text terms, to identify
      literature relating to circulating miRNAs in endometriosis published from 1996 to
      31 December 2017. Only peer-reviewed, full-text original research articles in
      English were included in the current review. The studies meeting the inclusion
      criteria were critically assessed and checked using the QUADAS-2 (Quality
      Assessment of Diagnostic Accuracy Studies) tool. The dysregulated miRNAs were
      assessed regarding the concordance between the various studies and their role in
      the disease. OUTCOMES: Nine studies were critically analysed, and 42 different
      miRNAs were found to be dysregulated in them, with only one common miRNA (miR
      20a) differentially expressed in more than one study. miR-17-5p/20a, miR-200, miR
      199a, miR-143, and miR-145 were explored for their pivotal role in the
      aetiopathogenesis of endometriosis. Wider implications: It is emerging that
      miRNAs play a central role in the pathogenesis of endometriosis and have the
      potential of being promising biomarkers. Circulating miRNAs as a non-invasive
      diagnostic tool may shorten the delay in the diagnosis of the disease, thus
      alleviating the suffering of women and reducing the burden on health care
      systems. However, despite numerous studies on circulating miRNAs in
      endometriosis, no single miRNA or any panel of them seems to meet the criteria of
      a diagnostic biomarker. The disagreement between the various studies upholds the
      demand of larger, well-controlled systematic validation studies with uniformity
      in the research approaches and involving diverse populations.

PMID- 29463006
TI  - Long-Term Oncologic Outcomes, Opioid Use, and Complications after Esophageal
      Cancer Surgery.
AB  - Effective and adequate opioid use and prevention of postoperative complications
      are important for enhanced recovery after surgery. We examined the effects of
      postoperative opioid use and postoperative complications on overall survival and
      recurrence-free survival after esophageal cancer surgery. This retrospective
      cohort study analyzed the records of patients diagnosed with esophageal cancer
      who underwent the Ivor Lewis operation between January 2005 and December 2011. We
      collected data on total opioid use for 8 days postoperatively, as well as
      information on postoperative complications (Clavien-Dindo classification). One
      hundred and twenty-one patients were included in the final analysis. Total opioid
      use was not significantly associated with overall survival (p = 0.520) and
      recurrence-free survival (p = 0.818). In contrast, the hazard ratio of
      postoperative overall survival was significantly higher with respect to Clavien
      Dindo classification 1-2 (hazard ratio: 2.009, p = 0.046), 3a-3b (hazard ratio:
      5.759, p < 0.001), and 4a-5 (hazard ratio: 3.982, p = 0.020) complications
      compared to no complications. Additionally, the hazard ratio of the recurrence
      free survival was significantly higher in class 1-2 complications (hazard ratio:
      2.336, p = 0.028) compared to none. Our study demonstrates that postoperative
      opioid use is not associated with survival and recurrence-free survival after
      esophageal cancer surgery, while postoperative complications may increase the
      hazard ratio for survival and recurrence-free survival.

PMID- 29463005
TI  - Mechanisms of Pulmonary Escape and Dissemination by Cryptococcus neoformans.
AB  - Cryptococcus neoformans is a common environmental saprophyte and human fungal
      pathogen that primarily causes disease in immunocompromised individuals. Similar
      to many environmentally acquired human fungal pathogens, C. neoformans initiates
      infection in the lungs. However, the main driver of mortality is invasive
      cryptococcosis leading to fungal meningitis. After C. neoformans gains a foothold
      in the lungs, a critical early step in invasion is transversal of the respiratory
      epithelium. In this review, we summarize current knowledge relating to pulmonary
      escape. We focus on fungal factors that allow C. neoformans to disseminate from
      the lungs via intracellular and extracellular routes.

PMID- 29463007
TI  - New Insights into the Role of Neuron-Specific Enolase in Neuro-Inflammation,
      Neurodegeneration, and Neuroprotection.
AB  - Neurodegeneration is a complex process that leads to irreversible neuronal damage
      and death in spinal cord injury (SCI) and various neurodegenerative diseases,
      which are serious, debilitating conditions. Despite exhaustive research, the
      cause of neuronal damage in these degenerative disorders is not completely
      understood. Elevation of cell surface alpha-enolase activates various
      inflammatory pathways, including the production of pro-inflammatory cytokines,
      chemokines, and some growth factors that are detrimental to neuronal cells. While
      alpha-enolase is present in all neurological tissues, it can also be converted to
      neuron specific enolase (NSE). NSE is a glycolytic enzyme found in neuronal and
      neuroendocrine tissues that may play a dual role in promoting both
      neuroinflammation and neuroprotection in SCI and other neurodegenerative events.
      Elevated NSE can promote ECM degradation, inflammatory glial cell proliferation,
      and actin remodeling, thereby affecting migration of activated macrophages and
      microglia to the injury site and promoting neuronal cell death. Thus, NSE could
      be a reliable, quantitative, and specific marker of neuronal injury. Depending on
      the injury, disease, and microenvironment, NSE may also show neurotrophic
      function as it controls neuronal survival, differentiation, and neurite
      regeneration via activation of phosphatidylinositol-4,5-bisphosphate 3-kinase
      (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways. This
      review discusses possible implications of NSE expression and activity in
      neuroinflammation, neurodegeneration, and neuroprotection in SCI and various
      neurodegenerative diseases for prognostic and therapeutic potential.

PMID- 29463008
TI  - Electronic Structure of C60/Zinc Phthalocyanine/V2O5 Interfaces Studied Using
      Photoemission Spectroscopy for Organic Photovoltaic Applications.
AB  - The interfacial electronic structures of a bilayer of fullerene (C60) and zinc
      phthalocyanine (ZnPc) grown on vanadium pentoxide (V2O5) thin films deposited
      using radio frequency sputtering under various conditions were studied using X
      ray and ultraviolet photoelectron spectroscopy. The energy difference between the
      highest occupied molecular orbital (HOMO) level of the ZnPc layer and the lowest
      unoccupied molecular orbital (LUMO) level of the C60 layer was determined and
      compared with that grown on an indium tin oxide (ITO) substrate. The energy
      difference of a heterojunction on all V2O5 was found to be 1.3~1.4 eV, while that
      on ITO was 1.1 eV. This difference could be due to the higher binding energy of
      the HOMO of ZnPc on V2O5 than that on ITO regardless of work functions of the
      substrates. We also determined the complete energy level diagrams of C60/ZnPc on
      V2O5 and ITO.

PMID- 29463010
TI  - Differences in Sirtuin Regulation in Response to Calorie Restriction in
      Cryptococcus neoformans.
AB  - Cryptococcus neoformans successfully replicates in low glucose in infected
      patients. In the serotype A strain, H99, growth in this condition prolongs
      lifespan regulated by SIR2, and can be modulated with SIR2-specific drugs.
      Previous studies show that lifespan modulation of a cryptococcal population
      affects its sensitivity to antifungals, and survival in an infection model.
      Sirtuins and their role in longevity are conserved among fungi; however, the
      effect of glucose starvation is not confirmed even in Saccharomyces cerevisiae.
      Lifespan analysis of C. neoformans strains in low glucose showed that 37.5%
      exhibited pro-longevity, and lifespan of a serotype D strain, RC2, was shortened.
      Transcriptome comparison of H99 and RC2 under calorie restriction demonstrated
      differences, confirmed by real-time PCR showing that SIR2, TOR1, SCH9, and PKA1
      expression correlated with lifespan response to calorie restriction. As expected,
      RC2-sir2Delta cells exhibited a shortened lifespan, which was reconstituted.
      However, shortened lifespan from calorie restriction was independent of SIR2. In
      contrast to H99 but consistent with altered SIR2 regulation, SIR2-specific drugs
      did not affect outcome of RC2 infection. These data suggest that SIR2 regulation
      and response to calorie restriction varies in C. neoformans, which should be
      considered when Sirtuins are investigated as potential therapy targets for fungal
      infections.

PMID- 29463009
TI  - Docosahexaenoic Acid Helps to Lessen Extinction Memory in Rats.
AB  - Abstract: Memory extinction is referred to as a learning process in which a
      conditioned response (CR) progressively reduces over time as an animal learns to
      uncouple a response from a stimulus. Extinction occurs when the rat is placed
      into a context without shock after training. Docosahexaenoic acid (DHA, C22:6, n
      3) is implicated in memory formation in mammalian brains. In a two-way active
      shuttle-avoidance apparatus, we examined whether DHA affects the extinction
      memory and the expression of brain cognition-related proteins, including gastrin
      releasing peptide receptor (GRPR), brain-derived neurotrophic factor receptor
      (BDNFR) tyrosine kinase receptor B (TrKB), and N-methyl-d-aspartate receptor
      (NMDAR) subunits NR2A and NR2B. Also, the protein levels of GRP, BDNF,
      postsynaptic density protein-95 (PSD-95), and vesicular acetylcholine transporter
      (VAChT), and the antioxidative potentials, in terms of lipid peroxide (LPO) and
      reactive oxygen species (ROS), were examined in the hippocampus. During the
      acquisition phase, the rats received a conditioned stimulus (CS-tone) paired with
      an unconditioned stimulus (UCS foot shock) for three consecutive days (Sessions
      S1, S2, and S3, each consisting of 30-trials) after 12 weeks of oral
      administration of DHA. After a three-day interval, the rats were re-subjected to
      two extinction sessions (S4, S5), each comprising 30 trials of CS alone. During
      the acquisition training in S1, the shock-related avoidance frequency
      (acquisition memory) was significantly higher in the DHA-administered rats
      compared with the control rats. The avoidance frequency, however, decreased with
      successive acquisition trainings in sessions S2 and S3. When the rats were
      subjected to the extinction sessions after a break for consolidation, the
      conditioned response (CR) was also significantly higher in the DHA-administered
      rats. Interestingly, the freezing responses (frequency and time) also
      significantly decreased in the DHA-administered rats, thus suggesting that a
      higher coping capacity was present during fear stress in the DHA-administered
      rats. DHA treatments increased the mRNA levels of GRPR, BDNF receptor TrKB, and
      NMDAR subunit NR2B. DHA also increased the protein levels of GRP, BDNF, PSD-95,
      and VAChT, and the antioxidative potentials in the hippocampus. These results
      suggest the usefulness of DHA for treating stress disorders.

PMID- 29463011
TI  - Inhibitory Activity of Allergic Contact Dermatitis and Atopic Dermatitis-Like
      Skin in BALB/c Mouse through Oral Administration of Fermented Barks of Alnus
      sibirica.
AB  - Phytochemical isolation of fermented Alnus sibirica (FAS) which was produced by
      using Lactobacillus plantarum subsp. argentoratensis, exhibited multiple and
      different composition compared with the original plant. Anti-allergic contact
      dermatitis (anti-ACD)/anti-atopic dermatitis (anti-AD) activities (visual
      observation and regulation of Th1/Th2 cytokines and IgE in blood) of FAS and the
      barks of Alnus sibirica extract (AS) and the two diarylheptanoids, hirsutenone
      (1) and muricarpon B (2), which are major components of FAS, were measured in
      vitro and in vivo. FAS, AS and the two compounds showed potent anti-oxidative,
      anti-inflammatory, anti-ACD and anti-AD activity. In particular, FAS showed more
      potent biological activity than AS. Thus, fermentation might be a prominent way
      to enhance the biological activity compared with the original plant. In addition,
      compounds (1) and (2) might be developed as functional materials or herbal
      medicines for ACD and AD.

PMID- 29463012
TI  - Using Micro-Molding and Stamping to Fabricate Conductive Polydimethylsiloxane
      Based Flexible High-Sensitivity Strain Gauges.
AB  - In this study, polydimethylsiloxane (PDMS) and conductive carbon nanoparticles
      were combined to fabricate a conductive elastomer PDMS (CPDMS). A high sensitive
      and flexible CPDMS strain sensor is fabricated by using stamping-process based
      micro patterning. Compared with conventional sensors, flexible strain sensors are
      more suitable for medical applications but are usually fabricated by
      photolithography, which suffers from a large number of steps and difficult mass
      production. Hence, we fabricated flexible strain sensors using a stamping-process
      with fewer processes than photolithography. The piezoresistive coefficient and
      sensitivity of the flexible strain sensor were improved by sensor pattern design
      and thickness change. Micro-patterning is used to fabricate various CPDMS
      microstructure patterns. The effect of gauge pattern was evaluated with ANSYS
      simulations. The piezoresistance of the strain gauges was measured and the gauge
      factor determined. Experimental results show that the piezoresistive coefficient
      of CPDMS is approximately linear. Gauge factor measurement results show that the
      gauge factor of a 140.0 MUm thick strain gauge with five grids is the highest.

PMID- 29463013
TI  - Precision Aliphatic Polyesters via Segmer Assembly Polymerization.
AB  - Precise structure-property relation of a biodegradable polymer (e.g., aliphatic
      polyester) is anticipated only if monomer units and chiral centers are arranged
      in a defined primary sequence as a biomacromolecule. An emerging synthetic
      methodology, namely segmer assembly polymerization (SAP), is introduced in this
      paper to reveal the latest progress in polyester synthesis. Almost any periodic
      polyester envisioned can be synthesized via SAP using a programed linear or
      cyclic monomer. In this context, the macroscopic properties of a biodegradable
      polymer are fundamentally determined by microstructural information through a
      bottom-up approach. It can be highlighted that SAP ideally combines the precision
      of organic synthesis and the high efficiency of a polymerization reaction.
      Previously reported strategies including nucleophilic displacement,
      polyesterification, cross-metathesis polymerization (CMP), ring-opening
      polymerization (ROP), ring-opening metathesis polymerization (ROMP) and entropy
      driven ring-opening metathesis polymerization (ED-ROMP) are critically reviewed
      in this paper to shed light on precision synthesis of aliphatic polyesters via
      SAP. Emerging yet challenging, SAP is a paradigm which reflects the convergence
      of organic and polymer chemistries and is also an efficient pathway to
      microstructural control. The current status, future challenges and promising
      trends in this realm are analyzed and discussed in this overview of the state-of
      the-art.

PMID- 29463014
TI  - Exploring the History of Chloroplast Capture in Arabis Using Whole Chloroplast
      Genome Sequencing.
AB  - Chloroplast capture occurs when the chloroplast of one plant species is
      introgressed into another plant species. The phylogenies of nuclear and
      chloroplast markers from East Asian Arabis species are incongruent, which
      indicates hybrid origin and shows chloroplast capture. In the present study, the
      complete chloroplast genomes of A. hirsuta, A. nipponica, and A. flagellosa were
      sequenced in order to analyze their divergence and their relationships. The
      chloroplast genomes of A. nipponica and A. flagellosa were similar, which
      indicates chloroplast replacement. If hybridization causing chloroplast capture
      occurred once, divergence between recipient species would be lower than between
      donor species. However, the chloroplast genomes of species with possible hybrid
      origins, A. nipponica and A. stelleri, differ at similar levels to possible
      maternal donor species A. flagellosa, which suggests that multiple hybridization
      events have occurred in their respective histories. The mitochondrial genomes
      exhibited similar patterns, while A. nipponica and A. flagellosa were more
      similar to each other than to A. hirsuta. This suggests that the two organellar
      genomes were co-transferred during the hybridization history of the East Asian
      Arabis species.

PMID- 29463016
TI  - Synthesis, Structural Property, Photophysical Property, Photocatalytic Property
      of Novel ZnBiErO4 under Visible Light Irradiation.
AB  - A novel photocatalyst ZnBiErO4 was firstly synthesized by solid-state reaction
      method and its structural and photocatalytic properties were analyzed by scanning
      electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and UV
      Vis diffuse reflectance. The results demonstrated that ZnBiErO4 crystallized with
      tetragonal crystal structure with space group I41/A. The lattice parameters for
      ZnBiErO4 were proved to be a = b = 10.255738 A and c = 9.938888 A. The band gap
      of ZnBiErO4 was estimated to be about 1.69 eV. Compared with nitrogen doped TiO2,
      ZnBiErO4 showed excellent photocatalytic activities for degrading methyl blue
      during visible light irradiation. The photocatalytic degradation of methyl blue
      with ZnBiErO4 or N-doped TiO2 as catalyst followed the first-order reaction
      kinetics. Moreover, the apparent first-order rate constant of ZnBiErO4 or N-doped
      TiO2 was 0.01607 min-1 or 0.00435 min-1. The reduction of total organic carbon,
      formation of inorganic products, such as SO42- and NO3- and the evolution of CO2
      revealed the continuous mineralization of methyl blue during the photocatalytic
      process. ZnBiErO4 photocatalyst had great potential to purify textile industry
      wastewater.

PMID- 29463015
TI  - Association between Bone Mineral Density of Femoral Neck and Geriatric
      Nutritional Risk Index in Rheumatoid Arthritis Patients Treated with Biological
      Disease-Modifying Anti-Rheumatic Drugs.
AB  - Treatment of rheumatoid arthritis (RA) with biological disease-modifying anti
      rheumatic drugs (bDMARDs) induces rapid remission. However, osteoporosis and its
      management remains a problem. The Geriatric Nutritional Risk Index (GNRI)
      evaluates the risk of malnutrition-related complications in elderly patients and
      has been shown to be a significant predictor of many diseases. We evaluated the
      correlation between GNRI and RA activity. In addition, risk factors for femoral
      neck bone loss were evaluated in RA patients treated with bDMARDs. We
      retrospectively examined the medical records of 146 patients with RA, collecting
      and recording the patients' demographic and clinical characteristics. Bone
      mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Inverse
      correlations were observed between GNRI and disease duration, disease activity
      score-28 joint count serum C-reactive protein (CRP), simple disease activity
      index, modified health assessment questionnaire score and CRP. GNRI showed
      correlation with femoral neck BMD and femoral neck BMD <= 70% of young adult men
      (YAM). Multiple regression analysis showed that female sex, increased age and
      lower GNRI were risk factors for lower BMD of the femoral neck. Multivariate
      binomial logistic regression analysis showed that female sex (odd ratio: 3.67)
      and lower GNRI (odd ratio: 0.87) were risk factors for BMD <= 70% of YAM. Because
      the GNRI is a simple method, it might be a simple predictor for RA activity and
      BMD status in RA patients. Complementary nutritional therapies might improve RA
      activity and osteoporosis in RA patients who have undergone treatment with
      bDMARDs.

PMID- 29463017
TI  - Identification of Novel Protein Kinase Receptor Type 2 Inhibitors Using
      Pharmacophore and Structure-Based Virtual Screening.
AB  - The Protein Kinase Receptor type 2 (RIPK2) plays an important role in the
      pathogenesis of inflammatory diseases; it signals downstream of the NOD1 and NOD2
      intracellular sensors and promotes a productive inflammatory response. However,
      excessive NOD2 signaling has been associated with various diseases, including
      sarcoidosis and inflammatory arthritis; the pharmacological inhibition of RIPK2
      is an affinity strategy that demonstrates an increased expression of pro
      inflammatory secretion activity. In this study, a pharmacophoric model based on
      the crystallographic pose of ponatinib, a potent RIPK2 inhibitor, and 30 other
      ones selected from the BindingDB repository database, was built. Compounds were
      selected based on the available ZINC compounds database and in silico predictions
      of their pharmacokinetic, toxicity and potential biological activity. Molecular
      docking was performed to identify the probable interactions of the compounds as
      well as their binding affinity with RIPK2. The compounds were analyzed to
      ponatinib and WEHI-345, which also used as a control. At least one of the
      compounds exhibited suitable pharmacokinetic properties, low toxicity and an
      interesting binding affinity and high fitness compared with the crystallographic
      pose of WEHI-345 in complex with RIPK2. This compound also possessed suitable
      synthetic accessibility, rendering it a potential and very promising RIPK2
      inhibitor to be further investigated in regards to different diseases,
      particularly inflammatory ones.

PMID- 29463018
TI  - Towards a Clinical Decision Support System for External Beam Radiation Oncology
      Prostate Cancer Patients: Proton vs. Photon Radiotherapy? A Radiobiological Study
      of Robustness and Stability.
AB  - We present a methodology which can be utilized to select proton or photon
      radiotherapy in prostate cancer patients. Four state-of-the-art competing
      treatment modalities were compared (by way of an in silico trial) for a cohort of
      25 prostate cancer patients, with and without correction strategies for prostate
      displacements. Metrics measured from clinical image guidance systems were used.
      Three correction strategies were investigated; no-correction, extended-no-action
      limit, and online-correction. Clinical efficacy was estimated via radiobiological
      models incorporating robustness (how probable a given treatment plan was
      delivered) and stability (the consistency between the probable best and worst
      delivered treatments at the 95% confidence limit). The results obtained at the
      cohort level enabled the determination of a threshold for likely clinical benefit
      at the individual level. Depending on the imaging system and correction strategy;
      24%, 32% and 44% of patients were identified as suitable candidates for proton
      therapy. For the constraints of this study: Intensity-modulated proton therapy
      with online-correction was on average the most effective modality. Irrespective
      of the imaging system, each treatment modality is similar in terms of robustness,
      with and without the correction strategies. Conversely, there is substantial
      variation in stability between the treatment modalities, which is greatly reduced
      by correction strategies. This study provides a 'proof-of-concept' methodology to
      enable the prospective identification of individual patients that will most
      likely (above a certain threshold) benefit from proton therapy.

PMID- 29463019
TI  - Health Differences between Roma and Non-Roma in the Slovak Dialyzed Population.
AB  - BACKGROUND: Roma health has not been studied systematically. Thus far, it has
      been shown that Roma compared to non-Roma have a significantly higher likelihood
      of getting end-stage renal disease and that their chances for survival on
      dialysis are lower. Evidence is lacking regarding morbidity between Roma and non
      Roma. The aim was to compare the health status of dialyzed Roma and non-Roma
      using the Charlson comorbidity index (CCI). All Slovak dialysis centers for
      adults were asked to fill in a questionaire with demographic and clinical data,
      including comorbidity. Cross-sectional analysis of 2082 patients with an average
      age of 63.8 +/- 13.8 years was performed. Comorbidity was expressed as the CCI,
      and ethnic differences were calculated. Linear regression was performed to adjust
      for differences in gender and age in both ethnic groups. Roma represented 13.0%
      of the whole dialyzed population (n = 270). Comorbidity expressed as CCI was
      significantly lower in the Roma population (p < 0.001). After adjusting for
      gender and age, ethnicity failed to be associated with the CCI in the linear
      regression analysis (p = 0.965, variance of the model-adjusted R2 38.6%). The
      health status of dialyzed Slovak Roma does not differ cross-sectionally when
      adjusted for age and gender from the health status of dialyzed non-Roma.

PMID- 29463020
TI  - Comparative Transcriptome Analysis Identifies Putative Genes Involved in Dioscin
      Biosynthesis in Dioscorea zingiberensis.
AB  - Dioscorea zingiberensis is a perennial herb native to China. The rhizome of D.
      zingiberensis has long been used as a traditional Chinese medicine to treat
      rheumatic arthritis. Dioscin is the major bioactive ingredient conferring the
      medicinal property described in Chinese pharmacopoeia. Several previous studies
      have suggested cholesterol as the intermediate to the biosynthesis of dioscin,
      however, the biosynthetic steps to dioscin after cholesterol remain unknown. In
      this study, a comprehensive D. zingiberensis transcriptome derived from its leaf
      and rhizome was constructed. Based on the annotation using various public
      databases, all possible enzymes in the biosynthetic steps to cholesterol were
      identified. In the late steps beyond cholesterol, cholesterol undergoes site
      specific oxidation by cytochrome P450s (CYPs) and glycosylation by UDP
      glycosyltransferases (UGTs) to yield dioscin. From the D. zingiberensis
      transcriptome, a total of 485 unigenes were annotated as CYPs and 195 unigenes
      with a sequence length above 1000 bp were annotated as UGTs. Transcriptomic
      comparison revealed 165 CYP annotated unigenes correlating to dioscin
      biosynthesis in the plant. Further phylogenetic analysis suggested that among
      those CYP candidates four of them would be the most likely candidates involved in
      the biosynthetic steps from cholesterol to dioscin. Additionally, from the UGT
      annotated unigenes, six of them were annotated as 3-O-UGTs and two of them were
      annotated as rhamnosyltransferases, which consisted of potential UGT candidates
      involved in dioscin biosynthesis. To further explore the function of the UGT
      candidates, two 3-O-UGT candidates, named Dz3GT1 and Dz3GT2, were cloned and
      functionally characterized. Both Dz3GT1 and Dz3GT2 were able to catalyze a C3
      glucosylation activity on diosgenin. In conclusion, this study will facilitate
      our understanding of dioscin biosynthesis pathway and provides a basis for
      further mining the genes involved in dioscin biosynthesis.

PMID- 29463022
TI  - HPT: A High Spatial Resolution Multispectral Sensor for Microsatellite Remote
      Sensing.
AB  - Although nano/microsatellites have great potential as remote sensing platforms,
      the spatial and spectral resolutions of an optical payload instrument are
      limited. In this study, a high spatial resolution multispectral sensor, the High
      Precision Telescope (HPT), was developed for the RISING-2 microsatellite. The HPT
      has four image sensors: three in the visible region of the spectrum used for the
      composition of true color images, and a fourth in the near-infrared region, which
      employs liquid crystal tunable filter (LCTF) technology for wavelength scanning.
      Band-to-band image registration methods have also been developed for the HPT and
      implemented in the image processing procedure. The processed images were compared
      with other satellite images, and proven to be useful in various remote sensing
      applications. Thus, LCTF technology can be considered an innovative tool that is
      suitable for future multi/hyperspectral remote sensing by nano/microsatellites.

PMID- 29463021
TI  - Dynamics of Bacterial and Fungal Communities during the Outbreak and Decline of
      an Algal Bloom in a Drinking Water Reservoir.
AB  - The microbial communities associated with algal blooms play a pivotal role in
      organic carbon, nitrogen and phosphorus cycling in freshwater ecosystems.
      However, there have been few studies focused on unveiling the dynamics of
      bacterial and fungal communities during the outbreak and decline of algal blooms
      in drinking water reservoirs. To address this issue, the compositions of
      bacterial and fungal communities were assessed in the Zhoucun drinking water
      reservoir using 16S rRNA and internal transcribed spacer (ITS) gene Illumina
      MiSeq sequencing techniques. The results showed the algal bloom was dominated by
      Synechococcus, Microcystis, and Prochlorothrix. The bloom was characterized by a
      steady decrease of total phosphorus (TP) from the outbreak to the decline period
      (p < 0.05) while Fe concentration increased sharply during the decline period (p
      < 0.05). The highest algal biomass and cell concentrations observed during the
      bloom were 51.7 mg/L and 1.9*108 cell/L, respectively. The cell concentration was
      positively correlated with CODMn (r = 0.89, p = 0.02). Illumina Miseq sequencing
      showed that algal bloom altered the water bacterial and fungal community
      structure. During the bloom, the dominant bacterial genus were Acinetobacter sp.,
      Limnobacter sp., Synechococcus sp., and Roseomonas sp. The relative size of the
      fungal community also changed with algal bloom and its composition mainly
      contained Ascomycota, Basidiomycota and Chytridiomycota. Heat map profiling
      indicated that algal bloom had a more consistent effect upon fungal communities
      at genus level. Redundancy analysis (RDA) also demonstrated that the structure of
      water bacterial communities was significantly correlated to conductivity and
      ammonia nitrogen. Meanwhile, water temperature, Fe and ammonia nitrogen drive the
      dynamics of water fungal communities. The results from this work suggested that
      water bacterial and fungal communities changed significantly during the outbreak
      and decline of algal bloom in Zhoucun drinking water reservoir. Our study
      highlights the potential role of microbial diversity as a driving force for the
      algal bloom and biogeochemical cycling of reservoir ecology.

PMID- 29463023
TI  - Characterization of the Body-to-Body Propagation Channel for Subjects during
      Sports Activities.
AB  - Body-to-body wireless networks (BBWNs) have great potential to find applications
      in team sports activities among others. However, successful design of such
      systems requires great understanding of the communication channel as the movement
      of the body components causes time-varying shadowing and fading effects. In this
      study, we present results of the measurement campaign of BBWN during running and
      cycling activities. Among others, the results indicated the presence of good and
      bad states with each state following a specific distribution for the considered
      propagation scenarios. This motivated the development of two-state semi-Markov
      model, for simulation of the communication channels. The simulation model was
      validated using the available measurement data in terms of first and second order
      statistics and have shown good agreement. The first order statistics obtained
      from the simulation model as well as the measured results were then used to
      analyze the performance of the BBWNs channels under running and cycling
      activities in terms of capacity and outage probability. Cycling channels showed
      better performance than running, having higher channel capacity and lower outage
      probability, regardless of the speed of the subjects involved in the measurement
      campaign.

PMID- 29463024
TI  - Overexpression of the Vitronectin V10 Subunit in Patients with Nonalcoholic
      Steatohepatitis: Implications for Noninvasive Diagnosis of NASH.
AB  - Nonalcoholic steatohepatitis (NASH) is the critical stage of nonalcoholic fatty
      liver disease (NAFLD). The persistence of necroinflammatory lesions and
      fibrogenesis in NASH is the leading cause of liver cirrhosis and, ultimately,
      hepatocellular carcinoma. To date, the histological examination of liver
      biopsies, albeit invasive, remains the means to distinguish NASH from simple
      steatosis (NAFL). Therefore, a noninvasive diagnosis by serum biomarkers is
      eagerly needed. Here, by a proteomic approach, we analysed the soluble low
      molecular-weight protein fragments flushed out from the liver tissue of NAFL and
      NASH patients. On the basis of the assumption that steatohepatitis leads to the
      remodelling of the liver extracellular matrix (ECM), NASH-specific fragments were
      in silico analysed for their involvement in the ECM molecular composition. The 10
      kDa C-terminal fragment of the ECM protein vitronectin (VTN) was then selected as
      a promising circulating biomarker in discriminating NASH. The analysis of sera of
      patients provided these major findings: the circulating VTN fragment (i) is
      overexpressed in NASH patients and positively correlates with the NASH activity
      score (NAS); (ii) originates from the disulfide bond reduction between the V10
      and the V65 subunits. In conclusion, V10 determination in the serum could
      represent a reliable tool for the noninvasive discrimination of NASH from simple
      steatosis.

PMID- 29463025
TI  - Inhibitory Influence of Panax notoginseng Saponins on Aspirin Hydrolysis in Human
      Intestinal Caco-2 Cells.
AB  - Herb-drug interactions are important safety concerns in clinical practice. The
      interactions occur firstly in the intestinal absorption for orally administered
      drugs. Aspirin and Panax notoginseng saponins (PNS)-based drugs are often
      combined in China to prevent larger-artery atherosclerosis. Here, we aimed to
      characterize the aspirin transport across Caco-2 cell monolayers, a model of the
      intestinal absorption, and further to evaluate the influence of PNS on aspirin
      hydrolysis and the relating mechanisms. Transcellular transport of aspirin and
      the influence of PNS were explored using Caco-2 cell monolayers. The protein
      expression of human carboxylesterase 1 (hCE1) and hCE2 in Caco-2 cells after PNS
      treatment was analyzed by ELISA, and the mRNA level were determined by qRT-PCR.
      In the study, Caco-2 cells showed high level of hydrolase activity, and most
      aspirin was hydrolyzed inside the cells during the transport process.
      Interestingly, PNS were demonstrated to inhibit the esterase activities
      responsible for aspirin hydrolysis in Caco-2 cells. PNS could also decrease the
      protein expression of hCE1 and hCE2, whereas exhibited minor effect on the mRNA
      expression. These results indicated that oral administration of PNS-based drugs
      might inhibit the hydrolysis of aspirin during intestinal absorption thus
      promoting its bioavailability.

PMID- 29463026
TI  - The Nile Rat (Arvicanthis niloticus) as a Superior Carbohydrate-Sensitive Model
      for Type 2 Diabetes Mellitus (T2DM).
AB  - Type II diabetes mellitus (T2DM) is a multifactorial disease involving complex
      genetic and environmental interactions. No single animal model has so far
      mirrored all the characteristics or complications of diabetes in humans. Since
      this disease represents a chronic nutritional insult based on a diet bearing a
      high glycemic load, the ideal model should recapitulate the underlying dietary
      issues. Most rodent models have three shortcomings: (1) they are genetically or
      chemically modified to produce diabetes; (2) unlike humans, most require high-fat
      feeding; (3) and they take too long to develop diabetes. By contrast, Nile rats
      develop diabetes rapidly (8-10 weeks) with high-carbohydrate (hiCHO) diets,
      similar to humans, and are protected by high fat (with low glycemic load) intake.
      This review describes diabetes progression in the Nile rat, including various
      aspects of breeding, feeding, and handling for best experimental outcomes. The
      diabetes is characterized by a striking genetic permissiveness influencing
      hyperphagia and hyperinsulinemia; random blood glucose is the best index of
      disease progression; and kidney failure with chronic morbidity and death are
      outcomes, all of which mimic uncontrolled T2DM in humans. Non-alcoholic fatty
      liver disease (NAFLD), also described in diabetic humans, results from hepatic
      triglyceride and cholesterol accumulation associated with rising blood glucose.
      Protection is afforded by low glycemic load diets rich in certain fibers or
      polyphenols. Accordingly, the Nile rat provides a unique opportunity to identify
      the nutritional factors and underlying genetic and molecular mechanisms that
      characterize human T2DM.

PMID- 29463027
TI  - The Connexin Mimetic Peptide Gap27 and Cx43-Knockdown Reveal Differential Roles
      for Connexin43 in Wound Closure Events in Skin Model Systems.
AB  - In the epidermis, remodelling of Connexin43 is a key event in wound closure.
      However, controversy between the role of connexin channel and non-channel
      functions exist. We compared the impact of SiRNA targeted to Connexin43 and the
      connexin mimetic peptide Gap27 on scrape wound closure rates and hemichannel
      signalling in adult keratinocytes (AK) and fibroblasts sourced from juvenile
      foreskin (JFF), human neonatal fibroblasts (HNDF) and adult dermal tissue (ADF).
      The impact of these agents, following 24 h exposure, on GJA1 (encoding
      Connexin43), Ki67 and TGF-beta1 gene expression, and Connexin43 and pSmad3
      protein expression levels, were examined by qPCR and Western Blot respectively.
      In all cell types Gap27 (100-100 MUM) attenuated hemichannel activity. In AK and
      JFF cells, Gap27 (100 nM-100 MUM) enhanced scrape wound closure rates by ~50% but
      did not influence movement in HNDF or ADF cells. In both JF and AK cells,
      exposure to Gap27 for 24 h reduced the level of Cx43 protein expression but did
      not affect the level in ADF and HNDF cells. Connexin43-SiRNA enhanced scrape
      wound closure in all the cell types under investigation. In HDNF and ADF,
      Connexin43-SiRNA enhanced cell proliferation rates, with enhanced proliferation
      also observed following exposure of HDNF to Gap27. By contrast, in JFF and AK
      cells no changes in proliferation occurred. In JFF cells, Connexin43-SiRNA
      enhanced TGF-beta1 levels and in JFF and ADF cells both Connexin43-SiRNA and
      Gap27 enhanced pSmad3 protein expression levels. We conclude that Connexin43
      signalling plays an important role in cell migration in keratinocytes and
      foreskin derived fibroblasts, however, different pathways are evoked and in
      dermal derived adult and neonatal fibroblasts, inhibition of Connexin43
      signalling plays a more significant role in regulating cell proliferation than
      cell migration.

PMID- 29463028
TI  - Italian Opuntia ficus-indica Cladodes as Rich Source of Bioactive Compounds with
      Health-Promoting Properties.
AB  - Natural by-products, especially phenolic compounds, are in great demand by the
      nutra-pharmaceutical and biomedical industries. An analytical study was performed
      to investigate, for the first time, the presence of antioxidant constituents and
      the corresponding in vitro antioxidant activity in the extract of cladodes from
      Ficodindia di San Cono (Opuntia ficus-indica) protected designation of origin
      (PDO). The cladode extracts were analysed for target determination of selected
      constituents, i.e. beta-polysaccharides and total phenolic content. Moreover, the
      antioxidant activity of hydro-alcoholic extracts was assessed by means of two
      different methods: alpha, alpha-diphenyl-beta-picrylhydrazyl (DPPH) free radical
      scavenging method and ferric reducing antioxidant power (FRAP) assay. An
      untargeted UHPLC-ESI-QTOF-MS profiling approach was used to depict the phenolic
      profile of hydro-alcoholic cladode extracts. Interestingly, over 2 g/kg of
      polyphenols were detected in this matrix, and these compounds were mainly
      responsible for the antioxidant properties, as shown by the strong correlation
      between phenolic classes and antioxidant scores. Finally, this study provides
      basic information on the presence of bioactive compounds and in vitro antioxidant
      activities in cladode extracts from cactus that might recommend their novel
      applications at the industrial level in the field of nutraceutical products.

PMID- 29463029
TI  - Nanoluciferase Reporter Gene System Directed by Tandemly Repeated Pseudo
      Palindromic NFAT-Response Elements Facilitates Analysis of Biological Endpoint
      Effects of Cellular Ca2+ Mobilization.
AB  - NFAT is a cytoplasm-localized hyper-phosphorylated transcription factor that is
      activated through dephosphorylation by calcineurin, a Ca2+/calmodulin-dependent
      phosphatase. A non-palindromic NFAT-response element (RE) found in the IL2
      promoter region has been commonly used for a Ca2+-response reporter gene system,
      but requirement of concomitant activation of AP-1 (Fos/Jun) often complicates the
      interpretation of obtained results. A new nanoluciferase (NanoLuc) reporter gene
      containing nine-tandem repeats of a pseudo-palindromic NFAT-RE located upstream
      of the IL8 promoter was designed to monitor Ca2+-induced transactivation activity
      of NFAT in human embryonic kidney (HEK) 293 cells by measuring luciferase
      activities of NanoLuc and co-expressed firefly luciferase for normalization.
      Ionomycin treatment enhanced the relative luciferase activity (RLA), which was
      suppressed by calcineurin inhibitors. HEK293 cells that stably express human
      STIM1 and Orai1, components of the store-operated calcium entry (SOCE) machinery,
      gave a much higher RLA by stimulation with thapsigargin, an inhibitor of
      sarcoplasmic/endoplamic reticulum Ca2+-ATPase (SERCA). HEK293 cells deficient in
      a penta-EF-hand Ca2+-binding protein ALG-2 showed a higher RLA value than the
      parental cells by stimulation with an acetylcholine receptor agonist carbachol.
      The novel reporter gene system is found to be useful for applications to cell
      signaling research to monitor biological endpoint effects of cellular Ca2+
      mobilization.

PMID- 29463030
TI  - Disaster Reintegration Model: A Qualitative Analysis on Developing Korean
      Disaster Mental Health Support Model.
AB  - This study sought to describe the mental health problems experienced by Korean
      disaster survivors, using a qualitative research method to provide empirical
      resources for effective disaster mental health support in Korea. Participants
      were 16 adults or elderly adults who experienced one or more disasters at least
      12 months ago recruited via theoretical sampling. Participants underwent in-depth
      individual interviews on their disaster experiences, which were recorded and
      transcribed for qualitative analysis, which followed Strauss and Corbin's (1998)
      Grounded theory. After open coding, participants' experiences were categorized
      into 130 codes, 43 sub-categories and 17 categories. The categories were further
      analyzed in a paradigm model, conditional model and the Disaster Reintegration
      Model, which proposed potentially effective mental health recovery strategies for
      disaster survivors, health providers and administrators. To provide effective
      assistance for mental health recovery of disaster survivors, both personal and
      public resilience should be promoted while considering both cultural and
      spiritual elements.

PMID- 29463031
TI  - Telomere Length Maintenance in Cancer: At the Crossroad between Telomerase and
      Alternative Lengthening of Telomeres (ALT).
AB  - Eukaryotic cells undergo continuous telomere shortening as a consequence of
      multiple rounds of replications. During tumorigenesis, cells have to acquire
      telomere DNA maintenance mechanisms (TMMs) in order to counteract telomere
      shortening, to preserve telomeres from DNA damage repair systems and to avoid
      telomere-mediated senescence and/or apoptosis. For this reason, telomere
      maintenance is an essential step in cancer progression. Most human tumors
      maintain their telomeres expressing telomerase, whereas a lower but significant
      proportion activates the alternative lengthening of telomeres (ALT) pathway.
      However, evidence about the coexistence of ALT and telomerase has been found both
      in vivo in the same cancer populations and in vitro in engineered cellular
      models, making the distinction between telomerase- and ALT-positive tumors
      elusive. Indeed, after the development of drugs able to target telomerase, the
      capability for some cancer cells to escape death, switching from telomerase to
      ALT, was highlighted. Unfortunately, to date, the mechanism underlying the
      possible switching or the coexistence of telomerase and ALT within the same cell
      or populations is not completely understood and different factors could be
      involved. In recent years, different studies have tried to shed light on the
      complex regulation network that controls the transition between the two TMMs,
      suggesting a role for embryonic cancer origin, epigenetic modifications, and
      specific genes activation-both in vivo and in vitro. In this review, we examine
      recent findings about the cancer-associated differential activation of the two
      known TMMs and the possible factors implicated in this process. Furthermore, some
      studies on cancers are also described that did not display any TMM.

PMID- 29463032
TI  - Comparative Study of the Detection of Chromium Content in Rice Leaves by 532 nm
      and 1064 nm Laser-Induced Breakdown Spectroscopy.
AB  - Fast detection of toxic metals in crops is important for monitoring pollution and
      ensuring food safety. In this study, laser-induced breakdown spectroscopy (LIBS)
      was used to detect the chromium content in rice leaves. We investigated the
      influence of laser wavelength (532 nm and 1064 nm excitation), along with the
      variations of delay time, pulse energy, and lens-to-sample distance (LTSD), on
      the signal (sensitivity and stability) and plasma features (temperature and
      electron density). With the optimized experimental parameters, univariate
      analysis was used for quantifying the chromium content, and several preprocessing
      methods (including background normalization, area normalization, multiplicative
      scatter correction (MSC) transformation and standardized normal variate (SNV)
      transformation were used to further improve the analytical performance. The
      results indicated that 532 nm excitation showed better sensitivity than 1064 nm
      excitation, with a detection limit around two times lower. However, the
      prediction accuracy for both excitation wavelengths was similar. The best result,
      with a correlation coefficient of 0.9849, root-mean-square error of 3.89 mg/kg
      and detection limit of 2.72 mg/kg, was obtained using the SNV transformed signal
      (Cr I 425.43 nm) induced by 532 nm excitation. The results indicate the inspiring
      capability of LIBS for toxic metals detection in plant materials.

PMID- 29463033
TI  - Spindle-E Acts Antivirally Against Alphaviruses in Mosquito Cells.
AB  - Mosquitoes transmit several human- and animal-pathogenic alphaviruses
      (Togaviridae family). In alphavirus-infected mosquito cells two different types
      of virus-specific small RNAs are produced as part of the RNA interference
      response: short-interfering (si)RNAs and PIWI-interacting (pi)RNAs. The siRNA
      pathway is generally thought to be the main antiviral pathway. Although an
      antiviral activity has been suggested for the piRNA pathway its role in host
      defences is not clear. Knock down of key proteins of the piRNA pathway (Ago3 and
      Piwi5) in Aedesaegypti-derived cells reduced the production of alphavirus
      chikungunya virus (CHIKV)-specific piRNAs but had no effect on virus replication.
      In contrast, knock down of the siRNA pathway key protein Ago2 resulted in an
      increase in virus replication. Similar results were obtained when expression of
      Piwi4 was silenced. Knock down of the helicase Spindle-E (SpnE), an essential co
      factor of the piRNA pathway in Drosophila melanogaster, resulted in increased
      virus replication indicating that SpnE acts as an antiviral against alphaviruses
      such as CHIKV and the related Semliki Forest virus (SFV). Surprisingly, this
      effect was found to be independent of the siRNA and piRNA pathways in Ae. aegypti
      cells and specific for alphaviruses. This suggests a small RNA-independent
      antiviral function for this protein in mosquitoes.

PMID- 29463034
TI  - Chronic Ketogenic Low Carbohydrate High Fat Diet Has Minimal Effects on Acid-Base
      Status in Elite Athletes.
AB  - Although short (up to 3 days) exposure to major shifts in macronutrient intake
      appears to alter acid-base status, the effects of sustained (>1 week)
      interventions in elite athletes has not been determined. Using a non-randomized,
      parallel design, we examined the effect of adaptations to 21 days of a ketogenic
      low carbohydrate high fat (LCHF) or periodized carbohydrate (PCHO) diet on pre-
      and post-exercise blood pH, and concentrations of bicarbonate (HCO3-) and lactate
      (La-) in comparison to a high carbohydrate (HCHO) control. Twenty-four (17 male
      and 7 female) elite-level race walkers completed 21 days of either LCHF (n = 9),
      PCHO (n = 7), or HCHO (n = 8) under controlled diet and training conditions. At
      baseline and post-intervention, blood pH, blood [HCO3-], and blood [La-] were
      measured before and after a graded exercise test. Net endogenous acid production
      (NEAP) over the previous 48-72 h was also calculated from monitored dietary
      intake. LCHF was not associated with significant differences in blood pH, [HCO3
      ], or [La-], compared with the HCHO diet pre- or post-exercise, despite a
      significantly higher NEAP (mEq.day-1) (95% CI = [10.44; 36.04]). Our results
      indicate that chronic dietary interventions are unlikely to influence acid-base
      status in elite athletes, which may be due to pre-existing training adaptations,
      such as an enhanced buffering capacity, or the actions of respiratory and renal
      pathways, which have a greater influence on regulation of acid-base status than
      nutritional intake.

PMID- 29463035
TI  - Nanomechanical Phenotype of Melanoma Cells Depends Solely on the Amount of
      Endogenous Pigment in the Cells.
AB  - Cancer cells have unique nanomechanical properties, i.e., they behave as if they
      were elastic. This property of cancer cells is believed to be one of the main
      reasons for their facilitated ability to spread and metastasize. Thus, the so
      called nanomechanical phenotype of cancer cells is viewed as an important
      indicator of the cells' metastatic behavior. One of the most highly metastatic
      cancer cells are melanoma cells, which have a very unusual property: they can
      synthesize the pigment melanin in large amounts, becoming heavily pigmented. So
      far, the role of melanin in melanoma remains unclear, particularly the impact of
      the pigment on metastatic behavior of melanoma cells. Importantly, until recently
      the potential mechanical role of melanin in melanoma metastasis was completely
      ignored. In this work, we examined melanoma cells isolated from hamster tumors
      containing endogenous melanin pigment. Applying an array of advanced microscopy
      and spectroscopy techniques, we determined that melanin is the dominating factor
      responsible for the mechanical properties of melanoma cells. Our results indicate
      that the nanomechanical phenotype of melanoma cells may be a reliable marker of
      the cells' metastatic behavior and point to the important mechanical role of
      melanin in the process of metastasis of melanoma.

PMID- 29463036
TI  - Physicochemical and Rheological Properties of a Dairy Dessert, Enriched with
      Chickpea Flour.
AB  - Dairy desserts are complex mixtures and matrices including main components such
      as milk, sugar, starch, hydrocolloids, colorants and flavors, with a
      proteinaceous structure; they are widely consumed and present a semisolid
      consistency. In this work, the physicochemical and rheological properties of a
      dairy dessert with the addition of chickpea flour (raw and cooked, at four
      concentrations) were studied to determine the effect of the flour. The results
      indicated that luminosity (L*: 62.75-83.29), pH (6.35-7.11) and acidity (1.56
      3.56) changed with the type of flour. The flow properties of the custards
      exhibited a non-Newtonian behavior that was well fitted by three flow models. The
      studied custard systems were stored for twelve days at 4  degrees C. The
      physicochemical and flow properties of the custards changed notably as a function
      of flour addition and storage time. From all samples, only four were analyzed
      with oscillatory tests, showing their mechanical spectra with elastic behavior.
      The dessert texture was also measured, founding that those formulated with Blanco
      Noroeste chickpea flour exhibited the highest values of hardness (0.356-0.391
      Newton (N)) through the twelve days. It can be concluded that those custard
      systems with the highest content of flour presented a very good response as a
      potential new dairy product.

PMID- 29463037
TI  - Antioxidant and Anti-Osteoporosis Activities of Chemical Constituents of the
      Stems of Zanthoxylum piperitum.
AB  - Two new lignans, zanthoxyloside C (1) and zanthoxyloside D (2), together with
      nine known compounds comprising lignans (3-5), flavonoids (6-8), and phenolics (9
      11), were isolated from the methanol extract of the stems of Zanthoxylum
      piperitum. All isolates were evaluated for their antioxidant and anti
      osteoporotic activities using oxygen radical absorbance capacity (ORAC), cupric
      reducing antioxidant capacity (CUPRAC), and tartrate-resistant acid phosphatase
      (TRAP) assays. Compounds 7-10 showed peroxyl radical-scavenging capacities and 4,
      6-7, and 9 showed reducing capacities. Moreover, compounds 3, 6-9, and 11
      significantly suppressed TRAP activities. These results indicated that the stems
      of Z. piperitum could be an excellent source for natural antioxidant and anti
      osteoporosis.

PMID- 29463038
TI  - Presence of TERT Promoter Mutations is a Secondary Event and Associates with
      Elongated Telomere Length in Myxoid Liposarcomas.
AB  - The occurrence of TERT promoter mutations has been well described in soft tissue
      sarcomas (STS). However, the biological role of these mutations as well as their
      impact on telomere length in STS is still unclear. We analyzed 116 patient
      samples diagnosed with 22 distinct histological subtypes of bone and STS for the
      occurrence of TERT promoter mutations by Sanger sequencing. We observed TERT
      promoter mutations at an overall frequency of 9.5% distributed over 7 different
      sarcoma subtypes. Except for one chondrosarcoma case harboring a C250T mutation,
      all other mutations were detected at location C228T. By far the far highest
      frequency of TERT promoter mutations was found in myxoid liposarcoma (MLS) (4 out
      of 9 cases studied, i.e., 44%). Assessment of telomere length from tumor biopsies
      revealed that TERT promoter-mutated MLSs had significantly fewer shortened
      telomeres in comparison to TERT wildtype MLSs. Based on the frequency of TERT
      promoter mutations and the elongated telomere length in mutated compared to
      wildtype MLS, we hypothesize that occurrence of TERT promoter mutations has a
      pivotal role in the disease progression as a secondary genetic event at a time
      when tumor cells face the need for telomere elongation to allow further
      proliferation.

PMID- 29463039
TI  - The Significance of MMP-1 in EGFR-TKI-Resistant Lung Adenocarcinoma: Potential
      for Therapeutic Targeting.
AB  - Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance
      is one of the most important problems in lung cancer therapy. Lung adenocarcinoma
      with EGFR-TKI resistance was reported to have higher abilities of invasion and
      migration than cancers sensitive to EGFR-TKI, but the function of matrix
      metalloproteinases (MMPs) has not been explored in EGFR-TKI-resistant lung
      adenocarcinoma. This study aims to clarify the significance of MMP-1 in EGFR-TKI
      resistant lung adenocarcinoma. From the results of in vitro studies of migration
      and invasion assays using EGFR-TKI-sensitive and -resistant cell lines and
      phosphorylation antibody arrays using EGF and rapamycin, we first demonstrate
      that overexpression of MMP-1, which might follow activation of a mammalian target
      of rapamycin (mTOR) pathway, plays an important role in the migration and
      invasion abilities of EGFR-TKI-resistant lung adenocarcinoma. Additionally,
      immunohistochemical studies using 89 cases of lung adenocarcinoma demonstrate
      that high expression of MMP-1 is significantly correlated with poor prognosis and
      factors such as smoking history and the subtype of invasive mucinous
      adenocarcinoma. These are consistent with the results of this in vitro study. To
      conclude, this study provides insights into the development of a possible
      alternative therapy manipulating MMP-1 and the mTOR signaling pathway in EGFR-TKI
      resistant lung adenocarcinoma.

PMID- 29463040
TI  - Structural Insights into sigma1 Receptor Interactions with Opioid Ligands by
      Molecular Dynamics Simulations.
AB  - Despite considerable advances over the past years in understanding the mechanisms
      of action and the role of the sigma1 receptor, several questions regarding this
      receptor remain unanswered. This receptor has been identified as a useful target
      for the treatment of a diverse range of diseases, from various central nervous
      system disorders to cancer. The recently solved issue of the crystal structure of
      the sigma1 receptor has made elucidating the structure-activity relationship
      feasible. The interaction of seven representative opioid ligands with the crystal
      structure of the sigma1 receptor (PDB ID: 5HK1) was simulated for the first time
      using molecular dynamics (MD). Analysis of the MD trajectories has provided the
      receptor-ligand interaction fingerprints, combining information on the crucial
      receptor residues and frequency of the residue-ligand contacts. The contact
      frequencies and the contact maps suggest that for all studied ligands, the
      hydrophilic (hydrogen bonding) interactions with Glu172 are an important factor
      for the ligands' affinities toward the sigma1 receptor. However, the hydrophobic
      interactions with Tyr120, Val162, Leu105, and Ile124 also significantly
      contribute to the ligand-receptor interplay and, in particular, differentiate the
      action of the agonistic morphine from the antagonistic haloperidol.

PMID- 29463042
TI  - Promotion of Vascular Morphogenesis of Endothelial Cells Co-Cultured with Human
      Adipose-Derived Mesenchymal Stem Cells Using Polycaprolactone/Gelatin Nanofibrous
      Scaffolds.
AB  - New blood vessel formation is essential for tissue regeneration to deliver oxygen
      and nutrients and to maintain tissue metabolism. In the field of tissue
      engineering, in vitro fabrication of new artificial vessels has been a
      longstanding challenge. Here we developed a technique to reconstruct a
      microvascular system using a polycaprolactone (PCL)/gelatin nanofibrous structure
      and a co-culture system. Using a simple electrospinning process, we fabricated
      three-dimensional mesh scaffolds to support the sprouting of human umbilical vein
      endothelial cells (HUVECs) along the electrospun nanofiber. The co-culture with
      adipose-derived mesenchymal stem cells (ADSCs) supported greater sprouting of
      endothelial cells (ECs). In a two-dimensional culture system, angiogenic cell
      assembly produced more effective direct intercellular interactions and paracrine
      signaling from ADSCs to assist in the vascular formation of ECs, compared to the
      influence of growth factor. Although vascular endothelial growth factor and
      sphingosine-1-phosphate were present during the culture period, the presence of
      ADSCs was the most important factor for the construction of a cell-assembled
      structure in the two-dimensional culture system. On the contrary, HUVECs co
      cultured on PCL/gelatin nanofiber scaffolds produced mature and functional
      microvessel and luminal structures with a greater expression of vascular markers,
      including platelet endothelial cell adhesion molecule-1 and podocalyxin.
      Furthermore, both angiogenic factors and cellular interactions with ADSCs through
      direct contact and paracrine molecules contributed to the formation of enhanced
      engineered blood vessel structures. It is expected that the co-culture system of
      HUVECs and ADSCs on bioengineered PCL/gelatin nanofibrous scaffolds will promote
      robust and functional microvessel structures and will be valuable for the
      regeneration of tissue with restored blood vessels.

PMID- 29463041
TI  - The Antioxidant Content and Protective Effect of Argan Oil and Syzygium
      aromaticum Essential Oil in Hydrogen Peroxide-Induced Biochemical and
      Histological Changes.
AB  - Oxidative stress is an important etiology of chronic diseases and many studies
      have shown that natural products might alleviate oxidative stress-induced
      pathogenesis. The study aims to evaluate the effect of Argan oil and Syzygium
      aromaticum essential oil on hydrogen peroxide (H2O2)-induced liver, brain and
      kidney tissue toxicity as well as biochemical changes in wistar rats. The
      antioxidant content of Argan oil and Syzygium aromaticum essential oil was
      studied with the use of gas chromatography. The animals received daily by gavage,
      for 21 days, either distilled water, Syzygium aromaticum essential oil, Argan
      oil, H2O2 alone, H2O2 and Syzygium aromaticum essential oil, or H2O2 and Argan
      oil. Blood samples were withdrawn on day 21 for the biochemical blood tests, and
      the kidney, liver and brain tissue samples were prepared for histopathology
      examination. The results showed that the content of antioxidant compounds in
      Syzygium aromaticum essential oil is higher than that found in Argan oil. H2O2
      increased level of blood urea, liver enzymes, total cholesterol, Low Density
      Lipoprotein (LDL-C), Triglycerides (TG) and Very Low Density Lipoprotein (VLDL),
      and decreased the total protein, albumin and High Density Lipoprotein-cholesterol
      (HDL-C). There was no significant effect on blood electrolyte or serum
      creatinine. The histopathology examination demonstrated that H2O2 induces
      dilatation in the central vein, inflammation and binucleation in the liver,
      congestion and hemorrhage in the brain, and congestion in the kidney. The H2O2
      induced histopathological and biochemical changes have been significantly
      alleviated by Syzygium aromaticum essential oil or Argan oil. It is concluded
      that the Argan oil and especially the mixture of Argan oil with Syzygium
      aromaticum essential oil can reduce the oxidative damage caused by H2O2, and this
      will pave the way to investigate the protective effects of these natural
      substances in the diseases attributed to the high oxidative stress.

PMID- 29463043
TI  - Non-Culture Diagnostics for Invasive Candidiasis: Promise and Unintended
      Consequences.
AB  - Blood cultures are positive for Candida species in < 50% and < 20% of
      hematogenously disseminated and intra-abdominal candidiasis, respectively. Non
      culture tests such as mannan, anti-mannan antibody, Candida albicans germ tube
      antibody (CAGTA), 1,3-beta-d-glucan (BDG), the T2Candida nanodiagnostic panel,
      and polymerase chain reaction (PCR) are available for clinical use, but their
      roles in patient care are uncertain. Sensitivity/specificity of combined
      mannan/anti-mannan, BDG, T2Candida and PCR for candidemia are ~80%/80%, ~80%/80%,
      ~90%/98%, and ~90%/90%, respectively. Limited data for intra-abdominal
      candidiasis suggest CAGTA, BDG sensitivity/specificity of ~65%/75% and PCR
      sensitivity of ~85-90%. PCR specificity has varied widely for intra-abdominal
      candidiasis (33-97%), and T2Candida data are lacking. Tests will be useful if
      restricted to cases in which positive and negative predictive values (PPVs, NPVs)
      differ in a clinically meaningful way from the pre-test likelihood of invasive
      candidiasis. In some patients, PPVs are sufficient to justify antifungal
      treatment, even if blood cultures are negative. In most patients, NPVs of each
      test are excellent, which may support decisions to withhold antifungal therapy.
      If test results are not interpreted judiciously, non-culture diagnostics may have
      unintended consequences for stewardship and infection prevention programs. In
      particular, discrepant non-culture test-positive/culture-negative results may
      promote inappropriate antifungal treatment of patients who are unlikely to have
      candidiasis, and lead to spurious reporting of hospital-acquired infections. In
      conclusion, non-culture Candida diagnostics have potential to advance patient
      care, but this promise will be realized only if users understand tests' strengths
      and limitations, and plan proactively for how best to employ them at their
      hospitals.

PMID- 29463045
TI  - Tunable Bandgap and Optical Properties of Black Phosphorene Nanotubes.
AB  - Black phosphorus (BP), a new two-dimensional material, has been the focus of
      scientists' attention. BP nanotubes have potential in the field of
      optoelectronics due to their low-dimensional effects. In this work, the bending
      strain energy, electronic structure, and optical properties of BP nanotubes were
      investigated by using the first-principles method based on density functional
      theory. The results show that these properties are closely related to the rolling
      direction and radius of the BP nanotube. All the calculated BP nanotube
      properties show direct bandgaps, and the BP nanotubes with the same rolling
      direction express a monotone increasing trend in the value of bandgap with a
      decrease in radius, which is a stacking effect of the compression strain on the
      inner atoms and the tension strain on the outer atoms. The bending strain energy
      of the zigzag phosphorene nanotubes (zPNTs) is higher than that of armchair
      phosphorene nanotubes (aPNT) with the same radius of curvature due to the
      anisotropy of the BP's structure. The imaginary part of the dielectric function,
      the absorption range, reflectivity, and the imaginary part of the refractive
      index of aPNTs have a wider range than those of zPNTs, with higher values
      overall. As a result, tunable BP nanotubes are suitable for optoelectronic
      devices, such as lasers and diodes, which function in the infrared and ultra
      violet regions, and for solar cells and photocatalysis.

PMID- 29463046
TI  - A Novel Hard Decision Based Simultaneous Target Tracking and Classification
      Approach.
AB  - Methods dealing with the problem of Joint Tracking and Classification (JTC) are
      abundant, among which Simultaneous Tracking and Classification (STC) provides a
      modularized scheme solving tracking and classification subproblems
      simultaneously. However, there is no explicit hard decision on the class label
      but only soft decision (class probability) is provided. This does not fit many
      practical cases, in which a hard decision is urgently needed. To solve this
      problem, this paper proposes a Hard decision-based STC (HSTC) method. HSTC takes
      all the decision error rate, timeliness, and estimation error into account.
      Specifically, for decision, the sequential probability ratio test is adopted due
      to its nice properties and also the adaptability to our situation. For
      estimation, by utilizing the two-way information exchange between the tracker and
      the classifier, we propose flexible three tracking schemes related to decision.
      The HSTC tracking result is divided into three parts according to the time of
      making the hard decision. In general, the proposed HSTC method takes advantage of
      both SPRT and STC. Finally, two illustrative JTC examples with hard decision
      verify the effectiveness of the the proposed HSTC method. They show that HSTC can
      meet the demand of the problem, and also has the performance superiority in both
      decision and estimation.

PMID- 29463044
TI  - The Role of the Estrogen Pathway in the Tumor Microenvironment.
AB  - Estrogen receptors are broadly expressed in many cell types involved in the
      innate and adaptive immune responses, and differentially regulate the production
      of cytokines. While both genomic and non-genomic tumor cell promoting mechanisms
      of estrogen signaling are well characterized in multiple carcinomas including
      breast, ovarian, and lung, recent investigations have identified a potential
      immune regulatory role of estrogens in the tumor microenvironment. Tumor immune
      tolerance is a well-established mediator of oncogenesis, with increasing evidence
      indicating the importance of the immune response in tumor progression. Immune
      based therapies such as antibodies that block checkpoint signals have emerged as
      exciting therapeutic approaches for cancer treatment, offering durable remissions
      and prolonged survival. However, only a subset of patients demonstrate clinical
      response to these agents, prompting efforts to elucidate additional
      immunosuppressive mechanisms within the tumor microenvironment. Evidence drawn
      from multiple cancer types, including carcinomas traditionally classified as non
      immunogenic, implicate estrogen as a potential mediator of immunosuppression
      through modulation of protumor responses independent of direct activity on tumor
      cells. Herein, we review the interplay between estrogen and the tumor
      microenvironment and the clinical implications of endocrine therapy as a novel
      treatment strategy within immuno-oncology.

PMID- 29463047
TI  - Human Intrinsic Factor Expression for Bioavailable Vitamin B12 Enrichment in
      Microalgae.
AB  - Dietary supplements and functional foods are becoming increasingly popular
      complements to regular diets. A recurring ingredient is the essential cofactor
      vitamin B12 (B12). Microalgae are making their way into the dietary supplement
      and functional food market but do not produce B12, and their B12 content is very
      variable. In this study, the suitability of using the human B12-binding protein
      intrinsic factor (IF) to enrich bioavailable B12 using microalgae was tested. The
      IF protein was successfully expressed from the nuclear genome of the model
      microalga Chlamydomonasreinhardtii and the addition of an N-terminal ARS2 signal
      peptide resulted in efficient IF secretion to the medium. Co-abundance of B12 and
      the secreted IF suggests the algal produced IF protein is functional and B12
      binding. Utilizing IF expression could be an efficient tool to generate B12
      enriched microalgae in a controlled manner that is suitable for vegetarians and,
      potentially, more bioavailable for humans.

PMID- 29463048
TI  - Trifluoromethyl Boron Dipyrromethene Derivatives as Potential Photosensitizers
      for Photodynamic Therapy.
AB  - In this study, two novel boron dipyrromethene-based photosensitizers (BDP3 and
      BDP6) substituted with three or six trifluoromethyl groups have been synthesized
      and characterized with various spectroscopic methods, and their photo-physical,
      photo-chemical, and photo-biological properties have also been explored. The two
      photosensitizers are highly soluble and remain nonaggregated in N,N
      dimethylformamide as shown by the intense and sharp Q-band absorption. Under red
      light irradiation (lambda = 660 nm, 1.5 J/cm2), both photosensitizers show high
      and comparable cytotoxicity towards HepG2 human hepatocarcinoma and HeLa human
      cervical carcinoma cells with IC50 values of 0.42-0.49 MUM. The high
      photocytotoxicity of BDP3 and BDP6 can be due to their high cellular uptake and
      low aggregation tendency in biological media, which result in a high efficiency
      to generate reactive oxygen species inside the cells. Confocal laser fluorescence
      microscopic studies indicate that they have superior selective affinities to the
      mitochondria and lysosomes of HepG2 and HeLa cells. The results show that these
      two trifluoromethyl boron dipyrromethene derivatives are potential anticancer
      agents for photodynamic therapy.

PMID- 29463049
TI  - The Anti-Cancer Effects of Frondoside A.
AB  - Frondoside A is a triterpenoid glycoside from the Atlantic Sea Cucumber,
      Cucumariafrondosa. Frondoside A has a broad spectrum of anti-cancer effects,
      including induction of cellular apoptosis, inhibition of cancer cell growth,
      migration, invasion, formation of metastases, and angiogenesis. In cell lines and
      animal models studied to date, the anti-cancer effects of the compound are seen
      in all solid cancers, lymphomas, and leukemias studied to date. These effects
      appear to be due to potent inhibition of p21-activated kinase 1 (PAK1), which is
      up-regulated in many cancers. In mouse models, frondoside A has synergistic
      effects with conventional chemotherapeutic agents, such as gemcitabine,
      paclitaxel, and cisplatin. Frondoside A administration is well-tolerated. No side
      effects have been reported and the compound has no significant effects on body
      weight, blood cells, or on hepatic and renal function tests after long-term
      administration. Frondoside A may be valuable in the treatment of malignancies,
      either as a single agent or in combination with other therapeutic modalities.

PMID- 29463051
TI  - Evidence of Adaptation to Recent Changes in Atmospheric CO2 in Four Weedy
      Species.
AB  - Seeds of three C3 and one C4 annual weedy species were collected from
      agricultural fields in Beltsville, Maryland in 1966 and 2006, when atmospheric
      CO2 concentrations averaged about 320 and 380 mol mol-1, respectively. Plants
      from each collection year were grown over a range of CO2 concentrations to test
      for adaptation of these weedy species to recent changes in atmospheric CO2. In
      all three of the C3 species, the increase in CO2 concentration from 320 mol mol-1
      to 380 mol mol-1 increased total dry mass at 24 days in plants from seeds
      collected in 2006, but not in plants from seeds collected in 1966. Shoot and seed
      dry mass at maturity was greater at the higher growth CO2 in plants collected in
      2006 than in 1966 in two of the species. Down-regulation of photosynthetic
      carboxylation capacity during growth at high CO2 was less in the newer seed lots
      than in the older in two of the species. Overall, the results indicate that
      adaptation to recent changes in atmospheric CO2 has occurred in some of these
      weedy species.

PMID- 29463050
TI  - Associations between Ambient Particulate Matter and Nitrogen Dioxide and Chronic
      Obstructive Pulmonary Diseases in Adults and Effect Modification by Demographic
      and Lifestyle Factors.
AB  - This study was undertaken to investigate the associations between chronic
      exposure to particulate matter of medium aerodynamic diameter <=10 or <=2.5 um
      (PM10 or PM2.5) and nitrogen dioxide (NO2) levels and lung function and to
      examine a possible change in these relationships by demographic and lifestyle
      factors. Chronic obstructive pulmonary disease (COPD) was defined using the
      Global Initiative for COPD criteria (forced expiratory volume in 1 second
      (FEV1)/forced vital capacity (FVC) of <70%). Associations of lung function and
      COPD with PM10 or PM2.5 or NO2 were examined using linear and logistic regression
      analyses among 1264 Korean adults. The highest tertiles of PM2.5 (>=37.1 MUg/m3)
      and NO2 (>=53.8 MUg/m3) exposure were significantly associated with COPD (highest
      versus lowest tertile of PM2.5: adjusted odds ratio (OR) = 1.79, 95% CI: 1.02
      3.13; highest versus lowest tertile of NO2: adjusted OR = 1.83, 95% CI: 1.04
      3.21). A 10 MUg/m3 increase in PM10 concentration was associated with a 1.85 L
      (95% CI -3.65 to -0.05) decrease in FEV1 and a 1.73 L (95% CI -3.35 to -0.12)
      decrease in FVC, with the strongest negative association among older people and
      those with less education. Reduced lung function was associated with PM2.5
      exposure in subjects with no physical activity. This study provides evidence that
      exposure to ambient air pollution has adverse effects on lung function in adults.

PMID- 29463052
TI  - Personalized Physical Activity Coaching: A Machine Learning Approach.
AB  - Living a sedentary lifestyle is one of the major causes of numerous health
      problems. To encourage employees to lead a less sedentary life, the Hanze
      University started a health promotion program. One of the interventions in the
      program was the use of an activity tracker to record participants' daily step
      count. The daily step count served as input for a fortnightly coaching session.
      In this paper, we investigate the possibility of automating part of the coaching
      procedure on physical activity by providing personalized feedback throughout the
      day on a participant's progress in achieving a personal step goal. The gathered
      step count data was used to train eight different machine learning algorithms to
      make hourly estimations of the probability of achieving a personalized, daily
      steps threshold. In 80% of the individual cases, the Random Forest algorithm was
      the best performing algorithm (mean accuracy = 0.93, range = 0.88-0.99, and mean
      F1-score = 0.90, range = 0.87-0.94). To demonstrate the practical usefulness of
      these models, we developed a proof-of-concept Web application that provides
      personalized feedback about whether a participant is expected to reach his or her
      daily threshold. We argue that the use of machine learning could become an
      invaluable asset in the process of automated personalized coaching. The
      individualized algorithms allow for predicting physical activity during the day
      and provides the possibility to intervene in time.

PMID- 29463053
TI  - Nutritional Composition and Antioxidant Properties of the Fruits of a Chinese
      Wild Passiflora foetida.
AB  - The aim of this work was to evaluate the main nutrients and their antioxidant
      properties of a Chinese wild edible fruit, Passiflora foetida, collected from the
      ecoregion of Hainan province, China. The analytical results revealed that P.
      foetida fruits were rich in amino acids (1097 mg/100 g in total), minerals
      (595.75 mg/100 g in total), and unsaturated fatty acids (74.18 g/100 g in total
      fat). The lyophilized powder of edible portion contained the higher polyphenols
      content than the inedible portion powder. The UPLC-Q-TOF-MSE analysis of the
      extractable and non-extractable phenolics indicated the presence of 65 compounds
      including 39 free phenolics, 14 insoluble-glycoside-phenolics, and 22 insoluble
      ester-phenolics. In addition, the non-extractable phenolics obtained by alkali
      hydrolysis showed significant antioxidant activities by/through DPPH and ABTS
      radical scavenging. These findings of P. foetida fruits, for the first time,
      suggest that these polyphenol-rich fruits may have potential nutraceutical
      efficacies.

PMID- 29463054
TI  - A Turn-on Fluorescence Sensor for Heparin Detection Based on a Release of Taiwan
      Cobra Cardiotoxin from a DNA Aptamer or Adenosine-Based Molecular Beacon.
AB  - This study presents two sensitive fluorescent assays for sensing heparin on the
      basis of the electrostatic interaction between heparin and Naja naja atra
      cardiotoxin 3 (CTX3). Owing to CTX3-induced folded structure of an adenosine
      based molecular beacon (MB) or a DNA aptamer against CTX3, a reduction in the
      fluorescent signal of the aptamer or MB 5'-end labeled with carboxyfluorescein
      (FAM) and 3'-end labeled with 4-([4-(dimethylamino)phenyl]azo)-benzoic acid
      (DABCYL) was observed upon the addition of CTX3. The presence of heparin and
      formation of the CTX3-heparin complex caused CTX3 detachment from the MB or
      aptamer, and restoration of FAM fluorescence of the 5'-FAM-and-3'-DABCYL-labeled
      MB and aptamer was subsequently noted. Moreover, the detection of heparin with
      these CTX3-aptamer and CTX3-MB sensors showed high sensitivity and selectivity
      toward heparin over chondroitin sulfate and hyaluronic acid regardless of the
      presence of plasma. The limit of detection for heparin in plasma was determined
      to be 16 ng/mL and 15 ng/mL, respectively, at a signal-to-noise ratio of 3. This
      study validates the practical utility of the CTX3-aptamer and CTX3-MB systems for
      determining the concentration of heparin in a biological matrix.

PMID- 29463055
TI  - Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects
      of Clinical Resistome and Potentiality of Horizontal Gene Transfer.
AB  - Antibiotic resistance poses an important threat to global public health and has
      become a challenge to modern medicine. The occurrence of antibiotic-resistant
      bacteria in a broad range of foods has led to a growing concern about the impact
      that food may have as a reservoir of antibiotic resistance genes. Considering
      Minas Frescal Cheese (MFC)-a typical Brazilian white soft cheese-and its economic
      and cultural values, in this study, medically relevant antimicrobial-resistance
      genetic markers (AR genes) were screened, and the occurrence of integrons were
      evaluated in manufactured MFC using culture-independent approaches. Through a
      fingerprinting analysis, the tested MFCs were brand-clustered, indicating
      reproducibility along the production chain. A common core of resistance markers
      in all brands evaluated and related antimicrobials such as beta-lactams,
      tetracyclines, quinolones, and sulfonamide was detected. Several other markers,
      including efflux pumps and aminoglycosides-resistance were distributed among
      brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of
      the samples. The presence of AR genes is of special interest due to their
      clinical relevance. Taken together, the data may suggest that the production
      chain of MFC might contribute to the spread of putative drug-resistant bacteria,
      which could greatly impact human health. Furthermore, detection of class 1 and
      class 2 integrons in MFC has led to discussions about resistance gene spread in
      this traditional cheese, providing evidence of potential horizontal transfer of
      AR genes to human gut microbiota.

PMID- 29463056
TI  - A Comparative Assessment of Biological Effects and Chemical Profile of Italian
      Asphodeline lutea Extracts.
AB  - The present study aims to highlight the therapeutic potential of Asphodeline
      lutea (AL), a wild edible plant of the Mediterranean diet. Roots, aerial parts,
      and flowers of AL at two different phenological stages were collected from three
      locations in Italy. The inhibitory activities of extracts on strategic enzymes
      linked to human diseases were assessed. The antioxidant properties were evaluated
      in vitro, using six standard bioassays. The phenolic and anthraquinone profiles
      were also established using HPLC-PDA. Zinc, cadmium, lead, and copper contents
      were also determined. All the samples inhibited acetylcholinesterase (from 1.51
      to 2.20 mg GALAEs/g extract), tyrosinase (from 7.50 to 25.3 mg KAEs/g extract),
      and alpha-amylase (from 0.37 to 0.51 mmol ACAEs/g extract). Aloe-emodin and
      physcion were present in all parts, while rhein was not detected. The phenolic
      profile and the heavy metals composition of specimens gathered from three
      different regions of Italy were different. It can be argued that samples
      collected near the street can contain higher concentrations of heavy metals. The
      experimental data confirm that the A. lutea species could be considered as a
      potential source of bioactive metabolites, and its consumption could play a
      positive and safe role in human health maintenance.

PMID- 29463058
TI  - Biosorption: An Interplay between Marine Algae and Potentially Toxic Elements-A
      Review.
AB  - In recent decades, environmental pollution has emerged as a core issue, around
      the globe, rendering it of fundamental concern to eco-toxicologists,
      environmental biologists, eco-chemists, pathologists, and researchers from other
      fields. The dissolution of polluting agents is a leading cause of environmental
      pollution of all key spheres including the hydrosphere, lithosphere, and
      biosphere, among others. The widespread occurrence of various pollutants
      including toxic heavy metals and other emerging hazardous contaminants is a
      serious concern. With increasing scientific knowledge, socioeconomic awareness,
      human health problems, and ecological apprehensions, people are more concerned
      about adverse health outcomes. Against this background, several removal methods
      have been proposed and implemented with the aim of addressing environmental
      pollution and sustainable and eco-friendly development. Among them, the
      biosorption of pollutants using naturally inspired sources, e.g., marine algae,
      has considerable advantages. In the past few years, marine algae have been
      extensively studied due to their natural origin, overall cost-effective ratio,
      and effectiveness against a broader pollutant range; thus, they are considered a
      potential alternative to the conventional methods used for environmental
      decontamination. Herein, an effort has been made to highlight the importance of
      marine algae as naturally inspired biosorbents and their role in biosorption.
      Biosorption mechanisms and factors affecting biosorption activities are also
      discussed in this review. The utilization of marine algae as a biosorbent for the
      removal of numerous potentially toxic elements has also been reviewed.

PMID- 29463057
TI  - Alternative Splicing of Transcription Factors Genes in Muscle Physiology and
      Pathology.
AB  - Skeletal muscle formation is a multi-step process that is governed by complex
      networks of transcription factors. The regulation of their functions is in turn
      multifaceted, including several mechanisms, among them alternative splicing (AS)
      plays a primary role. On the other hand, altered AS has a role in the
      pathogenesis of numerous muscular pathologies. Despite these premises, the causal
      role played by the altered splicing pattern of transcripts encoding myogenic
      transcription factors in neuromuscular diseases has been neglected so far. In
      this review, we systematically investigate what has been described about the AS
      patterns of transcription factors both in the physiology of the skeletal muscle
      formation process and in neuromuscular diseases, in the hope that this may be
      useful in re-evaluating the potential role of altered splicing of transcription
      factors in such diseases.

PMID- 29463059
TI  - Glutamine Synthetase: Localization Dictates Outcome.
AB  - Glutamine synthetase (GS) is the adenosine triphosphate (ATP)-dependent enzyme
      that catalyses the synthesis of glutamine by condensing ammonium to glutamate. In
      the circulatory system, glutamine carries ammonia from muscle and brain to the
      kidney and liver. In brain reduction of GS activity has been suggested as a
      mechanism mediating neurotoxicity in neurodegenerative disorders. In cancer, the
      delicate balance between glutamine synthesis and catabolism is a critical event.
      In vitro evidence, confirmed in vivo in some cases, suggests that reduced GS
      activity in cancer cells associates with a more invasive and aggressive
      phenotype. However, GS is known to be highly expressed in cells of the tumor
      microenvironment, such as fibroblasts, adipocytes and immune cells, and their
      ability to synthesize glutamine is responsible for the acquisition of protumoral
      phenotypes. This has opened a new window into the complex scenario of the tumor
      microenvironment, in which the balance of glutamine consumption versus glutamine
      synthesis influences cellular function. Since GS expression responds to glutamine
      starvation, a lower glutamine synthesizing power due to the absence of GS in
      cancer cells might apply a metabolic pressure on stromal cells. This event might
      push stroma towards a GS-high/protumoral phenotype. When referred to stromal
      cells, GS expression might acquire a 'bad' significance to the point that GS
      inhibition might be considered a conceivable strategy against cancer metastasis.

PMID- 29463060
TI  - Chitin Oligosaccharide Modulates Gut Microbiota and Attenuates High-Fat-Diet
      Induced Metabolic Syndrome in Mice.
AB  - Gut microbiota has been proved to be an indispensable link between nutrient
      excess and metabolic syndrome, and chitin oligosaccharide (NACOS) has displayed
      therapeutic effects on multiple diseases such as cancer and gastritis. In this
      study, we aim to confirm whether NACOS can ameliorate high-fat diet (HFD)-induced
      metabolic syndrome by rebuilding the structure of the gut microbiota community.
      Male C57BL/6J mice fed with HFD were treated with NACOS (1 mg/mL) in drinking
      water for five months. The results indicate that NACOS improved glucose metabolic
      disorder in HFD-fed mice and suppressed mRNA expression of the protein regulators
      related to lipogenesis, gluconeogenesis, adipocyte differentiation, and
      inflammation in adipose tissues. Additionally, NACOS inhibited the destruction of
      the gut barrier in HFD-treated mice. Furthermore, 16S ribosome RNA sequencing of
      fecal samples demonstrates that NACOS promoted the growth of beneficial
      intestinal bacteria remarkably and decreased the abundance of inflammogenic taxa.
      In summary, NACOS partly rebuilt the microbial community and improved the
      metabolic syndrome of HFD-fed mice. These data confirm the preventive effects of
      NACOS on nutrient excess-related metabolic diseases.

PMID- 29463062
TI  - Palliative Care for Children in Hospital: Essential Roles.
AB  - Palliative care for children in pediatric hospitals is a vital part of the
      network of services supporting children with severe illness. This has been
      recognized, with a trend over the past decade for an increased number of
      pediatric palliative care (PPC) services established in pediatric hospitals. The
      inpatient team is in the unique position of influencing the early identification
      of children and their families, across the age and diagnostic spectrum, which
      could benefit from palliative care. These services have an opportunity to
      influence the integration of the palliative approach throughout the hospital, and
      in so doing, have the capacity to improve many aspects of care, including
      altering an increasingly futile and burdensome treatment trajectory, and ensuring
      improved symptom (physical and psychological) management.

PMID- 29463061
TI  - Wnt Signaling and Its Impact on Mitochondrial and Cell Cycle Dynamics in
      Pluripotent Stem Cells.
AB  - The core transcriptional network regulating stem cell self-renewal and
      pluripotency remains an intense area of research. Increasing evidence indicates
      that modified regulation of basic cellular processes such as mitochondrial
      dynamics, apoptosis, and cell cycle are also essential for pluripotent stem cell
      identity and fate decisions. Here, we review evidence for Wnt regulation of
      pluripotency and self-renewal, and its connections to emerging features of
      pluripotent stem cells, including (1) increased mitochondrial fragmentation, (2)
      increased sensitivity to cell death, and (3) shortened cell cycle. We provide a
      general overview of the stem cell-specific mechanisms involved in the maintenance
      of these uncharacterized hallmarks of pluripotency and highlight potential links
      to the Wnt signaling pathway. Given the physiological importance of stem cells
      and their enormous potential for regenerative medicine, understanding fundamental
      mechanisms mediating the crosstalk between Wnt, organelle-dynamics, apoptosis,
      and cell cycle will be crucial to gain insight into the regulation of stemness.

PMID- 29463064
TI  - Devising Mobile Sensing and Actuation Infrastructure with Drones.
AB  - Vast applications and services have been enabled as the number of mobile or
      sensing devices with communication capabilities has grown. However, managing the
      devices, integrating networks or combining services across different networks has
      become a new problem since each network is not directly connected via back-end
      core networks or servers. The issue is and has been discussed especially in
      wireless sensor and actuator networks (WSAN). In such systems, sensors and
      actuators are tightly coupled, so when an independent WSAN needs to collaborate
      with other networks, it is difficult to adequately combine them into an
      integrated infrastructure. In this paper, we propose drone-as-a-gateway (DaaG),
      which uses drones as mobile gateways to interconnect isolated networks or combine
      independent services. Our system contains features that focus on the service
      being provided in the order of importance, different from an adaptive simple
      mobile sink system or delay-tolerant system. Our simulation results have shown
      that the proposed system is able to activate actuators in the order of importance
      of the service, which uses separate sensors' data, and it consumes almost the
      same time in comparison with other path-planning algorithms. Moreover, we have
      implemented DaaG and presented results in a field test to show that it can enable
      large-scale on-demand deployment of sensing and actuation infrastructure or the
      Internet of Things (IoT).

PMID- 29463065
TI  - Paediatric Palliative Care in Resource-Poor Countries.
AB  - There is a great need for paediatric palliative care (PPC) services globally, but
      access to services is lacking in many parts of the world, particularly in
      resource-poor settings. Globally it is estimated that 21.6 million children need
      access to palliative care, with 8.2 needing specialist services. PC has been
      identified as important within the global health agenda e.g., within universal
      health coverage, and a recent Lancet commission report recognised the need for
      PPC. However, a variety of challenges have been identified to PPC development
      globally such as: access to treatment, access to medications such as oral
      morphine, opiophobia, a lack of trained health and social care professionals, a
      lack of PPC policies and a lack of awareness about PPC. These challenges can be
      overcome utilising a variety of strategies including advocacy and public
      awareness, education, access to medications, implementation and research.
      Examples will be discussed impacting on the provision of PPC in resource-poor
      settings. High-quality PPC service provision can be provided with resource-poor
      settings, and there is an urgent need to scale up affordable, accessible, and
      quality PPC services globally to ensure that all children needing palliative care
      can access it.

PMID- 29463066
TI  - OASL1 Traps Viral RNAs in Stress Granules to Promote Antiviral Responses.
AB  - Oligoadenylate synthetase (OAS) protein family is the major interferon (IFN)
      stimulated genes responsible for the activation of RNase L pathway upon viral
      infection. OAS-like (OASL) is also required for inhibition of viral growth in
      human cells, but the loss of one of its mouse homolog, OASL1, causes a severe
      defect in termination of type I interferon production. To further investigate the
      antiviral activity of OASL1, we examined its subcellular localization and
      regulatory roles in IFN production in the early and late stages of viral
      infection. We found OASL1, but not OASL2, formed stress granules trapping viral
      RNAs and promoted efficient RLR signaling in early stages of infection. Stress
      granule formation was dependent on RNA binding activity of OASL1. But in the late
      stages of infection, OASL1 interacted with IRF7 transcripts to inhibit
      translation resulting in down regulation of IFN production. These results
      implicate that OASL1 plays context dependent functions in the antiviral response
      for the clearance and resolution of viral infections.

PMID- 29463067
TI  - Liraglutide Inhibits the Apoptosis of MC3T3-E1 Cells Induced by Serum Deprivation
      through cAMP/PKA/beta-Catenin and PI3K/AKT/GSK3beta Signaling Pathways.
AB  - In recent years, the interest towards the relationship between incretins and bone
      has been increasing. Previous studies have suggested that glucagon-like peptide-1
      (GLP-1) and its receptor agonists exert beneficial anabolic influence on skeletal
      metabolism, such as promoting proliferation and differentiation of osteoblasts
      via entero-osseous-axis. However, little is known regarding the effects of GLP-1
      on osteoblast apoptosis and the underlying mechanisms involved. Thus, in the
      present study, we investigated the effects of liraglutide, a glucagon-like
      peptide-1 receptor agonist, on apoptosis of murine MC3T3-E1 osteoblastic cells.
      We confirmed the presence of GLP-1 receptor (GLP-1R) in MC3T3-E1 cells. Our data
      demonstrated that liraglutide inhibited the apoptosis of osteoblastic MC3T3-E1
      cells induced by serum deprivation, as detected by Annexin V/PI and Hoechst 33258
      staining and ELISA assays. Moreover, liraglutide upregulated Bcl-2 expression and
      downregulated Bax expression and caspase-3 activity at intermediate concentration
      (100 nM) for maximum effect. Further study suggested that liraglutide stimulated
      the phosphorylation of AKT and enhanced cAMP level, along with decreased
      phosphorylation of GSK3beta, increased beta-catenin phosphorylation at Ser675
      site and upregulated nuclear beta-catenin content and transcriptional activity.
      Pretreatment of cells with the PI3K inhibitor LY294002, PKA inhibitor H89, and
      siRNAs GLP-1R, beta-catenin abrogated the liraglutide-induced activation of cAMP,
      AKT, beta-catenin, respectively. In conclusion, these findings illustrate that
      activation of GLP-1 receptor by liraglutide inhibits the apoptosis of
      osteoblastic MC3T3-E1 cells induced by serum deprivation through cAMP/PKA/beta
      catenin and PI3K/Akt/GSK3beta signaling pathways.

PMID- 29463063
TI  - The Yeast Saccharomyces cerevisiae as a Model for Understanding RAS Proteins and
      their Role in Human Tumorigenesis.
AB  - The exploitation of the yeast Saccharomyces cerevisiae as a biological model for
      the investigation of complex molecular processes conserved in multicellular
      organisms, such as humans, has allowed fundamental biological discoveries. When
      comparing yeast and human proteins, it is clear that both amino acid sequences
      and protein functions are often very well conserved. One example of the high
      degree of conservation between human and yeast proteins is highlighted by the
      members of the RAS family. Indeed, the study of the signaling pathways regulated
      by RAS in yeast cells led to the discovery of properties that were often found
      interchangeable with RAS proto-oncogenes in human pathways, and vice versa. In
      this work, we performed an updated critical literature review on human and yeast
      RAS pathways, specifically highlighting the similarities and differences between
      them. Moreover, we emphasized the contribution of studying yeast RAS pathways for
      the understanding of human RAS and how this model organism can contribute to
      unveil the roles of RAS oncoproteins in the regulation of mechanisms important in
      the tumorigenic process, like autophagy.

PMID- 29463068
TI  - Benzidine Induces Epithelial-Mesenchymal Transition of Human Bladder Cancer Cells
      through Activation of ERK5 Pathway.
AB  - Benzidine, a known carcinogen, is closely associated with the development of
      bladder cancer (BC). Epithelial-mesenchymal transition (EMT) is a critical
      pathophysiological process in BC progression. The underlying molecular mechanisms
      of mitogen-activated protein kinase (MAPK) pathway, especially extracellular
      regulated protein kinases 5 (ERK5), in regulating benzidine-induced EMT remains
      unclarified. Hence, two human bladder cell lines, T24 and EJ, were utilized in
      our study. Briefly, cell migration was assessed by wound healing assay, and cell
      invasion was determined by Transwell assay. Quantitative PCR and western blot
      were utilized to determine both gene expressions as well as protein levels of EMT
      and MAPK, respectively. Small interfering RNA (siRNA) was transfected to further
      determine ERK5 function. As a result, the migration and invasion abilities were
      enhanced, epithelial marker expression was decreased while mesenchymal marker
      expression was increased in human BC cell lines. Meanwhile, benzidine
      administration led to activation of ERK5 and activator protein 1 (AP-1) proteins,
      without effective stimulation of the Jun N-terminal kinase (JNK) or p38 pathways.
      Moreover, Benzidine-induced EMT and ERK5 activation were completely suppressed by
      XMD8-92 and siRNAs specific to ERK5. Of note, ERK1/2 was activated in benzidine
      treated T24 cells, while benzidine-induced EMT could not be reversed by U0126, an
      ERK1/2 inhibitor, as indicated by further study. Collectively, our findings
      revealed that ERK5-mediated EMT was critically involved in benzidine-correlated
      BC progression, indicating the therapeutic significance of ERK5 in benzidine
      related BC.

PMID- 29463069
TI  - Regulation of Ethylene Biosynthesis by Phytohormones in Etiolated Rice (Oryza
      sativa L.) Seedlings.
AB  - The gaseous hormone ethylene influences many aspects of plant growth,
      development, and responses to a variety of stresses. The biosynthesis of ethylene
      is tightly regulated by various internal and external stimuli, and the primary
      target of the regulation is the enzyme 1-aminocyclopropane-1-carboxylic acid
      (ACC) synthase (ACS), which catalyzes the rate-limiting step of ethylene
      biosynthesis. We have previously demonstrated that the regulation of ethylene
      biosynthesis is a common feature of most of the phytohormones in etiolated
      Arabidopsis seedlings via the modulation of the protein stability of ACS. Here,
      we show that various phytohormones also regulate ethylene biosynthesis from
      etiolated rice seedlings in a similar manner to those in Arabidopsis. Cytokinin,
      brassinosteroids, and gibberellic acid increase ethylene biosynthesis without
      changing the transcript levels of neither OsACS nor ACC oxidases (OsACO), a
      family of enzymes catalyzing the final step of the ethylene biosynthetic pathway.
      Likewise, salicylic acid and abscisic acid do not alter the gene expression of
      OsACS, but both hormones downregulate the transcript levels of a subset of ACO
      genes, resulting in a decrease in ethylene biosynthesis. In addition, we show
      that the treatment of the phytohormones results in distinct etiolated seedling
      phenotypes, some of which resemble ethylene-responsive phenotypes, while others
      display ethylene-independent morphologies, indicating a complicated hormone
      crosstalk in rice. Together, our study brings a new insight into crosstalk
      between ethylene biosynthesis and other phytohormones, and provides evidence that
      rice ethylene biosynthesis could be regulated by the post-transcriptional
      regulation of ACS proteins.

PMID- 29463071
TI  - Hypoxia Upregulates Mitotic Cyclins Which Contribute to the Multipotency of Human
      Mesenchymal Stem Cells by Expanding Proliferation Lifespan.
AB  - Hypoxic culture is widely recognized as a method to efficiently expand human
      mesenchymal stem cells (MSCs) without loss of stem cell properties. However, the
      molecular basis of how hypoxia priming benefits MSC expansion remains unclear. In
      this report, our systemic quantitative proteomic and RT-PCR analyses revealed the
      involvement of hypoxic conditioning activated genes in the signaling process of
      the mitotic cell cycle. Introduction of screened two mitotic cyclins, CCNA2 and
      CCNB1, significantly extended the proliferation lifespan of MSCs in normoxic
      condition. Our results provide important molecular evidence that multipotency of
      human MSCs by hypoxic conditioning is determined by the mitotic cell cycle
      duration. Thus, the activation of mitotic cyclins could be a potential strategy
      to the application of stem cell therapy.

PMID- 29463070
TI  - Cigarette Smoke Extract Enhances IL-17A-Induced IL-8 Production via Up-Regulation
      of IL-17R in Human Bronchial Epithelial Cells.
AB  - Interleukin-17A (IL-17A) is a pro-inflammatory cytokine mainly derived from T
      helper 17 cells and is known to be involved in the pathogenesis of chronic
      obstructive pulmonary disease (COPD). Cigarette smoke (CS) has been considered as
      a primary risk factor of COPD. However, the interaction between CS and IL-17A and
      the underlying molecular mechanisms have not been clarified. In the current
      study, we investigated the effects of cigarette smoke extract (CSE) on IL-17A
      induced IL-8 production in human bronchial epithelial cells, and sought to
      identify the underlying molecular mechanisms. IL-8 production was significantly
      enhanced following treatment with both IL-17A and CSE, while treatment with
      either IL-17A or CSE alone caused only a slight increase in IL-8 production. CSE
      increased the transcription of IL-17RA/RC and surface membrane expression of IL
      17R, which was suppressed by an inhibitor of the phosphoinositide 3-kinase
      (PI3K)/Akt pathway (LY294002). CSE caused inactivation of glycogen synthase
      kinase-3beta (GSK-3beta) via the PI3K/Akt pathway. Blockade of GSK-3beta
      inactivation by overexpression of constitutively active GSK-3beta (S9A)
      completely suppressed the CSE-induced up-regulation of IL-17R expression and the
      CSE-induced enhancement of IL-8 secretion. In conclusion, inactivation of GSK
      3beta via the PI3K/Akt pathway mediates CSE-induced up-regulation of IL-17R,
      which contributes to the enhancement of IL-17A-induced IL-8 production.

PMID- 29463072
TI  - The Effects of Donepezil, an Acetylcholinesterase Inhibitor, on Impaired Learning
      and Memory in Rodents.
AB  - A previous study in humans demonstrated the sustained inhibitory effects of
      donepezil on acetylcholinesterase (AChE) activity; however, the effective
      concentration of donepezil in humans and animals is unclear. This study aimed to
      characterize the effective concentration of donepezil on AChE inhibition and
      impaired learning and memory in rodents. A pharmacokinetic study of donepezil
      showed a mean peak plasma concentration of donepezil after oral treatment (3 and
      10 mg/kg) of approximately 1.2 +/- 0.4 h and 1.4 +/- 0.5 h, respectively;
      absolute bioavailability was calculated as 3.6%. Further, AChE activity was
      inhibited by increasing plasma concentrations of donepezil, and a maximum
      inhibition of 31.5 +/- 5.7% was observed after donepezil treatment in hairless
      rats. Plasma AChE activity was negatively correlated with plasma donepezil
      concentration. The pharmacological effects of donepezil are dependent upon its
      concentration and AChE activity; therefore, we assessed the effects of donepezil
      on learning and memory using a Y-maze in mice. Donepezil treatment (3 mg/kg)
      significantly prevented the progression of scopolamine-induced memory impairment
      in mice. As the concentration of donepezil in the brain increased, the recovery
      of spontaneous alternations also improved; maximal improvement was observed at
      46.5 +/- 3.5 ng/g in the brain. In conclusion, our findings suggest that the AChE
      inhibitory activity and pharmacological effects of donepezil can be predicted by
      the concentration of donepezil. Further, 46.5 +/- 3.5 ng/g donepezil is an
      efficacious target concentration in the brain for treating learning and memory
      impairment in rodents.

PMID- 29463074
TI  - Diabetes insipidus in pregnancy: how to advice the patient?
AB  - Diabetes insipidus, characterized by polyuria and polydipsia, is a rare disease
      during pregnancy. Nevertheless, its recognition is important to avoid
      complications due to dehydration and hypernatremia. Its manifestation during
      pregnancy ranges from exacerbation of pre-existing central or nephrogenic
      diabetes insipidus to transient pregnancy-induced diabetes insipidus due to the
      increased metabolism of the antidiuretic hormone vasopressin (AVP) by the
      placental vasopressinase. Diagnosis can be challenging, as urinary frequency is
      common during pregnancy and primary polydipsia also needs to be excluded. Also,
      the standard water deprivation test is not recommended during pregnancy due to
      the increased risk of complications. Treatment depends upon the final diagnosis,
      with desmopressin (DDAVP) being the medication of choice in AVP-deficient
      diabetes insipidus, whereas nephrogenic diabetes insipidus requires treatment of
      the underlying disease and supportive measures.

PMID- 29463073
TI  - T-Type Calcium Channels Are Required to Maintain Viability of Neural Progenitor
      Cells.
AB  - T-type calcium channels are low voltage-activated calcium channels that evoke
      small and transient calcium currents. Recently, T-type calcium channels have been
      implicated in neurodevelopmental disorders such as autism spectrum disorder and
      neural tube defects. However, their function during embryonic development is
      largely unknown. Here, we investigated the function and expression of T-type
      calcium channels in embryonic neural progenitor cells (NPCs). First, we compared
      the expression of T-type calcium channel subtypes (CaV3.1, 3.2, and 3.3) in NPCs
      and differentiated neural cells (neurons and astrocytes). We detected all
      subtypes in neurons but not in astrocytes. In NPCs, CaV3.1 was the dominant
      subtype, whereas CaV3.2 was weakly expressed, and CaV3.3 was not detected. Next,
      we determined CaV3.1 expression levels in the cortex during early brain
      development. Expression levels of CaV3.1 in the embryonic period were transiently
      decreased during the perinatal period and increased at postnatal day 11. We then
      pharmacologically blocked T-type calcium channels to determine the effects in
      neuronal cells. The blockade of T-type calcium channels reduced cell viability,
      and induced apoptotic cell death in NPCs but not in differentiated astrocytes.
      Furthermore, blocking T-type calcium channels rapidly reduced AKT-phosphorylation
      (Ser473) and GSK3beta-phosphorylation (Ser9). Our results suggest that T-type
      calcium channels play essential roles in maintaining NPC viability, and T-type
      calcium channel blockers are toxic to embryonic neural cells, and may potentially
      be responsible for neurodevelopmental disorders.

PMID- 29463075
TI  - Adverse effects of doping with anabolic androgenic steroids in competitive
      athletics, recreational sports and bodybuilding.
AB  - Despite the fact that sports organizations and legislators have introduced
      various mechanisms to discourage athletes from using performance and appearance
      enhancing substances a high percentage of athletes admits to their unabated
      application. In competitive athletics, bodybuilding and in recreational sports
      anabolic androgenic steroids (AAS) continue to be the substances most abused.
      This review summarizes the side effects of AAS abuse on organs and system
      functions in both sexes. High doses of AAS cause a significant increase of
      erythrocytes and hemoglobin concentration, which may lead to thromboembolism,
      intracardiac thrombosis and stroke. Long-term AAS abusers have a higher incidence
      of arrhythmias, atherosclerosis, concentric left-ventricular myocardial
      hypertrophy with impaired diastolic function and also sudden cardiac death.
      Changes of liver function and structure, up to hepatocellular carcinoma, have
      been described, mainly in cases of chronic misuse of 17alpha-alkylated AAS.
      Sleeplessness, increased irritability, depressive mood status are often observed
      in AAS abuse. In former AAS abusers depression, anxiety and melancholy may
      persist for many years. Due to negative feedback in the regulation of the
      hypothalamic-pituitary-gonadal axis AAS can cause reversible suppression of
      spermatogenesis up to azoospermia. In women the changes most often caused by AAS
      abuse are hirsutism, irreversible deepening of voice, dysmenorrhea, secondary
      amenorrhea with anovulation and infertility. AAS abuse notwithstanding, under
      clinical conditions testosterone remains the most important hormone for
      substitution therapy of male hypogonadism.

PMID- 29463076
TI  - Acute pituitary disease in pregnancy: how to handle hypophysitis and Sheehan's
      syndrome.
AB  - Pregnancy-related hypophysitis (PR-Hy) that typically occurs during late
      pregnancy and the early postpartum period is considered an autoimmune disorder.
      Knowledge and awareness of characteristic clinical symptoms and specific
      endocrine and neuroradiological features mostly enables a correct diagnosis and
      guarantees best possible management. In the presence of mild clinical symptoms, a
      "wait-and-watch" approach is recommended. Transsphenoidal surgery or
      glucocorticoid therapy is indicated if progressive clinical signs or severe
      visual symptoms are observed. Reported cases indicate that transsphenoidal
      surgery performed during pregnancy can reverse visual symptoms and has a minimal
      risk to the health of the fetus and mother. Glucocorticoid therapy has a high
      initial response rate, but recurrence can occur after discontinuation. In late
      pregnancy hypophysitis, the options of delaying therapy until the child is born
      or, if symptoms are severe, of inducing delivery prior to therapy have to be
      considered. Sheehan's syndrome (SS) is characterized by irreversible, partial or
      complete hypopituitarism due to pituitary infarction. The predominating causative
      event is massive peripartum hemorrhage (PPH). A considerable diagnostic delay is
      mostly observed. PPH and the typical postpartum findings of agalactia and
      amenorrhea should alert for the diagnosis of SS and prompt endocrine evaluation.
      Timely hormone replacement therapy is paramount to reduce morbidity and mortality
      and improve quality of life of afflicted women. Adrenal failure is a major
      endocrinological risk both of hypophysitis and of Sheehan syndrome. Early
      recognition and treatment is paramount to avoid life-threatening adrenal crisis.

PMID- 29463077
TI  - Technical considerations of a tailored rigid endoscopic evacuation of ventricular
      hemorrhage.

PMID- 29463078
TI  - Current endovascular management of complex pararenal aneurysms.
AB  - INTRODUCTION: Endovascular approach to abdominal aortic aneurysm has increased in
      frequency over the last decade and is preferred by many practitioners and
      patients alike. However, its role in "complex" aneurysms with challenging
      anatomy, short neck length, or borderline landing zone for grafts is less well
      understood. Additionally, the endovascular role in complex urgent or emergent
      repairs has not been adequately studied. Several techniques have been developed
      in order to address these concerns and further the endovascular approach. This
      article seeks to describe incidents in which an endovascular approach may be
      challenging, describe the most popular techniques now available for approaching
      these cases, and present the best literature available for considering these
      techniques. EVIDENCE ACQUISITION: Medline searches were performed with the key
      words "complex endovascular aneurysm repair," "fenestrated endovascular aneurysm
      repair," "chimney grafts" and "snorkel grafts" to gain access to available data.
      EVIDENCE SYNTHESIS: Articles were reviewed for results and technical
      considerations. CONCLUSIONS: By employing increasingly complex endovascular
      techniques, complex pararenal aneurysms can be successfully treated in an
      endovascular fashion.

PMID- 29463079
TI  - Prevention of venous thromboembolism through the implementation of a risk
      assessment tool: a comparative study in medical and surgical patients.
AB  - BACKGROUND: Hospitalized patients are at high risk of venous thromboembolism
      (VTE). Underutilization of thromboprophylaxis remains common despite existing
      clinical guidelines. The aim is to evaluate the implementation of a state wide
      standardized adult VTE risk assessment tool (RAT) to assist in the screening of
      inpatients and prescribing of appropriate thromboprophylaxis. METHODS: In total,
      234 patients were audited using clinical notes and spot assessments for VTE risk
      at Western Sydney Local Health District over a two year period. Patients were
      stratified into pre- (N.=132) and postimplementation (N.=102) of the RAT.
      Intervention involved continuing education of staff and passive dissemination of
      guidelines. Prescription of pharmacological and mechanical prophylaxis and the
      development of thromboembolic events were evaluated. RESULTS: Overall, 39.0% of
      medical and 63.0% of surgical patients were risk assessed during
      preimplementation versus 39.2% and 92.2% during postimplementation of the RAT
      (P<0.0001). Usage of pharmacological prophylaxis increased from 72% to 79% and
      mechanical prophylaxis from 41% to 48%. VTE rates in moderate to high risk
      medical patients decreased from 15.2% preimplementation to 6.5%
      postimplementation. Rates of non-fatal and fatal pulmonary embolism (PE) were
      2.3% and 0.8% respectively prior compared to 1.0% and 0.0% postimplementation.
      CONCLUSIONS: Standardized VTE RAT increased thromboprophylaxis usage and
      decreased PE rates, with a greater improvement reflected in surgical patients.
      These findings highlight the importance of a multifaceted approach to VTE
      prevention using regular audits with feedback, electronic reminders systems,
      prescribing tools and continuing education.

PMID- 29463080
TI  - Rheological Characteristics of 2D Titanium Carbide (MXene) Dispersions: A Guide
      for Processing MXenes.
AB  - Understanding the rheological properties of two-dimensional (2D) materials in
      suspension is critical for the development of various solution processing and
      manufacturing techniques. 2D carbides and nitrides (MXenes) constitute one of the
      largest families of 2D materials with >20 synthesized compositions and
      applications already ranging from energy storage to medicine to optoelectronics.
      However, in spite of a report on clay-like behavior, not much is known about
      their rheological response. In this study, rheological behavior of single- and
      multilayer Ti3C2T x in aqueous dispersions was investigated. Viscous and
      viscoelastic properties of MXene dispersions were studied over a variety of
      concentrations from colloidal dispersions to high loading slurries, showing that
      a multilayer MXene suspension with up to 70 wt % can exhibit flowability.
      Processing guidelines for the fabrication of MXene films, coatings, and fibers
      have been established based on the rheological properties. Surprisingly, high
      viscosity was observed at very low concentrations for solutions of single-layer
      MXene flakes. Single-layer colloidal solutions were found to exhibit partial
      elasticity even at the lowest tested concentrations (<0.20 mg/mL) due to the
      presence of strong surface charge and excellent hydrophilicity of MXene, making
      them amenable to fabrication at dilute concentrations. Overall, the findings of
      this study provide fundamental insights into the rheological response of this
      quickly growing 2D family of materials in aqueous environments as well as offer
      guidelines for processing of MXenes.

PMID- 29463081
TI  - Regioselective Synthesis of N2-Alkylated-1,2,3 Triazoles and N1-Alkylated
      Benzotriazoles: Cu2S as a Recyclable Nanocatalyst for Oxidative Amination of N, N
      Dimethylbenzylamines.
AB  - Copper chalcogenide nanoparticles (Cu2S) synthesized for the first time from a
      single-source precursor, CuSPh, act as highly efficient and reusable
      heterogeneous catalyst for regioselective amination of N, N-dimethylbenzylamines
      with various azoles. The reaction involves N-H/C-H cross-dehydrogenative coupling
      (CDC) and demonstrates wide functional group tolerance. It provides highly
      selective access to N1-alkylated benzotriazoles, N2-alkylated 1,2,3-triazoles and
      4-phenyl-1,2,3-triazoles, and N-alkylated carbazoles in 70-89% yields under
      solvent-free conditions. The Cu2S nanocatalyst has been characterized by PXRD,
      XPS, SEM-EDX, and HR-TEM analysis. Mechanistic studies suggest that the reaction
      follows a radical pathway and involves an iminium ion intermediate.

PMID- 29463082
TI  - Changes in Dissolved Organic Matter Composition and Disinfection Byproduct
      Precursors in Advanced Drinking Water Treatment Processes.
AB  - Molecular changes in dissolved organic matter (DOM) from treatment processes at
      two drinking water treatment plants in Japan were investigated using unknown
      screening analysis by Orbitrap mass spectrometry. DOM formulas with carbon,
      hydrogen and oxygen (CHO-DOM) were the most abundant class in water samples, and
      over half of them were commonly found at both plants. Among the treatment
      processes, ozonation induced the most drastic changes to DOM. Mass peak
      intensities of less saturated CHO-DOM (positive (oxygen subtracted double bond
      equivalent per carbon (DBE-O)/C)) decreased by ozonation, while more saturated
      oxidation byproducts (negative (DBE-O)/C) increased and new oxidation byproducts
      (OBPs) were detected. By Kendrick mass analysis, ozone reactions preferred less
      saturated CHO-DOM in the same alkylation families and produced more saturated
      alkylation families of OBPs. Following ozonation, biological activated carbon
      filtration effectively removed <300 Da CHO-DOM, including OBPs. Following
      chlorination, over 50 chlorinated formulas of disinfection byproducts (DBPs) were
      found in chlorinated water samples where at least half were unknown. Putative
      precursors of these DBPs were determined based on electrophilic substitutions and
      addition reactions. Ozonation demonstrated better decomposition of addition
      reaction-type precursors than electrophilic substitution-type precursors; over
      half of both precursor types decreased during biological activated carbon
      filtration.

PMID- 29463083
TI  - Shear Rheology Control of Wrinkles and Patterns in Graphene Oxide Films.
AB  - Drying graphene oxide (GO) films are subject to extensive wrinkling, which
      largely affects their final properties. Wrinkles were shown to be suitable in
      biotechnological applications; however, they negatively affect the electronic
      properties of the films. Here, we report on wrinkle tuning and patterning of GO
      films under stress-controlled conditions during drying. GO flakes assemble at an
      air-solvent interface; the assembly forms a skin at the surface and may bend due
      to volume shrinkage while drying. We applied a modification of evaporative
      lithography to spatially define the evaporative stress field. Wrinkle alignment
      is achieved over cm2 areas. The wavelength (i.e., wrinkle spacing) is controlled
      in the MUm range by the film thickness and GO concentration. Furthermore, we
      propose the use of nanoparticles to control capillary forces to suppress
      wrinkling. An example of a controlled pattern is given to elucidate the potential
      of the technique. The results are discussed in terms of classical elasticity
      theory. Wrinkling is the result of bending of the wet solid skin layer assembled
      on a highly elastic GO dispersion. Wavelength selection is the result of energy
      minimization between the bending of the skin and the elastic deformation of the
      GO supporting dispersion. The results strongly suggest the possibility to tune
      wrinkles and patterns by simple physicochemical routes.

PMID- 29463084
TI  - 18F-AlF Labeled Peptide and Protein Conjugates as Positron Emission Tomography
      Imaging Pharmaceuticals.
AB  - The clinical applications of positron emission tomography (PET) imaging
      pharmaceuticals have increased tremendously over the past several years since the
      approval of 18fluorine-fluorodeoxyglucose (18F-FDG) by the Food and Drug
      Administration (FDA). Numerous 18F-labeled target-specific potential imaging
      pharmaceuticals, based on small and large molecules, have been evaluated in
      preclinical and clinical settings. 18F-labeling of organic moieties involves the
      introduction of the radioisotope by C-18F bond formation via a nucleophilic or an
      electrophilic substitution reaction. However, biomolecules, such as peptides,
      proteins, and oligonucleotides, cannot be radiolabeled via a C-18F bond formation
      as these reactions involve harsh conditions, including organic solvents, high
      temperature, and nonphysiological conditions. Several approaches, including 18F
      labeled prosthetic groups, silicon, boron, and aluminum fluoride acceptor
      chemistry, and click chemistry have been developed, in the past, for 18F labeling
      of biomolecules. Linear and macrocyclic polyaminocarboxylates and their analogs
      and derivatives form thermodynamically stable and kinetically inert aluminum
      chelates. Hence, macrocyclic polyaminocarboxylates have been used for conjugation
      with biomolecules, such as folate, peptides, affibodies, and protein fragments,
      followed by 18F-AlF chelation, and evaluation of their targeting abilities in
      preclinical and clinical environments. The goal of this report is to provide an
      overview of the 18F radiochemistry and 18F-labeling methodologies for small
      molecules and target-specific biomolecules, a comprehensive review of
      coordination chemistry of Al3+, 18F-AlF labeling of peptide and protein
      conjugates, and evaluation of 18F-labeled biomolecule conjugates as potential
      imaging pharmaceuticals.

PMID- 29463085
TI  - Spectroscopic and DFT Characterization of a Highly Reactive Nonheme FeV-Oxo
      Intermediate.
AB  - The reaction of [(PyNMe3)FeII(CF3SO3)2], 1, with excess peracetic acid at -40 
      degrees C generates a highly reactive intermediate, 2b(PAA), that has the fastest
      rate to date for oxidizing cyclohexane by a nonheme iron species. It exhibits an
      intense 490 nm chromophore associated with an S = 1/2 EPR signal having g-values
      at 2.07, 2.01, and 1.94. This species was shown to be in a fast equilibrium with
      a second S = 1/2 species, 2a(PAA), assigned to a low-spin acylperoxoiron(III)
      center. Unfortunately, contaminants accompanying the 2(PAA) samples prevented
      determination of the iron oxidation state by Mossbauer spectroscopy. Use of MeO
      PyNMe3 (an electron-enriched version of PyNMe3) and cyclohexyl peroxycarboxylic
      acid as oxidant affords intermediate 3b(CPCA) with a Mossbauer isomer shift delta
      = -0.08 mm/s that indicates an iron(V) oxidation state. Analysis of the Mossbauer
      and EPR spectra, combined with DFT studies, demonstrates that the electronic
      ground state of 3b(CPCA) is best described as a quantum mechanical mixture of
      [(MeO-PyNMe3)FeV(O)(OC(O)R)]2+ (~75%) with some FeIV(O)(*OC(O)R) and
      FeIII(OOC(O)R) character. DFT studies of 3b(CPCA) reveal that the unbound oxygen
      of the carboxylate ligand, O2, is only 2.04 A away from the oxo group, O1,
      corresponding to a Wiberg bond order for the O1-O2 bond of 0.35. This unusual
      geometry facilitates reversible O1-O2 bond formation and cleavage and accounts
      for the high reactivity of the intermediate when compared to the rates of
      hydrogen atom transfer and oxygen atom transfer reactions of FeIII(OC(O)R) ferric
      acyl peroxides and FeIV(O) complexes. The interaction of O2 with O1 leads to a
      significant downshift of the Fe-O1 Raman frequency (815 cm-1) relative to the 903
      cm-1 value predicted for the hypothetical [(MeO-PyNMe3)FeV(O)(NCMe)]3+ complex.

PMID- 29463086
TI  - Highly Active NiO Photocathodes for H2O2 Production Enabled via Outer-Sphere
      Electron Transfer.
AB  - Tandem dye-sensitized photoelectrosynthesis cells are promising architectures for
      the production of solar fuels and commodity chemicals. A key bottleneck in the
      development of these architectures is the low efficiency of the photocathodes,
      leading to small current densities. Herein, we report a new design principle for
      highly active photocathodes that relies on the outer-sphere reduction of a
      substrate from the dye, generating an unstable radical that proceeds to the
      desired product. We show that the direct reduction of dioxygen from dye
      sensitized nickel oxide (NiO) leads to the production of H2O2. In the presence of
      oxygen and visible light, NiO photocathodes sensitized with commercially
      available porphyrin, coumarin, and ruthenium dyes exhibit large photocurrents (up
      to 400 MUA/cm2) near the thermodynamic potential for O2/H2O2 in near-neutral
      water. Bulk photoelectrolysis of porphyrin-sensitized NiO over 24 h results in
      millimolar concentrations of H2O2 with essentially 100% faradaic efficiency. To
      our knowledge, these are among the most active NiO photocathodes reported for
      multiproton/multielectron transformations. The photoelectrosynthesis proceeds by
      initial formation of superoxide, which disproportionates to H2O2. This
      disproportionation-driven charge separation circumvents the inherent challenges
      in separating electron-hole pairs for photocathodes tethered to inner sphere
      electrocatalysts and enables new applications for photoelectrosynthesis cells.

PMID- 29463088
TI  - Global Neuroscience: China.

PMID- 29463090
TI  - Assessment and Treatment Considerations for Post Traumatic Stress Disorder at End
      of Life.
AB  - Post traumatic stress disorder (PTSD) may first emerge, reemerge, or worsen as
      individuals approach end of life and may complicate the dying process.
      Unfortunately, lack of awareness of the occurrence and/or manifestation of PTSD
      at end of life can lead to PTSD going unaddressed. Even if PTSD is properly
      diagnosed, traditional evidence-based trauma-focused treatments may not be
      feasible or advisable with this group as many patients at end of life often lack
      the physical and mental stamina to participate in traditional psychotherapy. This
      article reviews the clinical and empirical literature on PTSD at end of life, as
      well as discusses assessment and psychotherapy treatment issues with this
      neglected population. In addition, it expands on the current reviews of this
      literature1-3 by extrapolating results from nontraditional treatment approaches
      with other patient populations. Elements of these approaches with patients
      sharing similar characteristics and/or comorbidities with patients with PTSD at
      end of life may provide additional benefits for the latter population. Clinical
      implications and suggestions for interdisciplinary care providers are provided.

PMID- 29463091
TI  - Urinary Tract Infections: Pilot Study to Improve Guideline Adherence.

PMID- 29463092
TI  - Super-Utilization of Health Care Resources Among Gynecologic Oncology Patients.
AB  - Super-utilizers account for many emergency department visits (EDV) and
      hospitalizations. Among Medicare/Medicaid patients, 5% to 10% account for >50% of
      spending. Little is known about super-utilization in gynecologic oncology. Charts
      of 64 gynecologic oncology patients with >=3 EDV and/or admissions over 12 months
      were reviewed retrospectively. Cancer type distribution was 47% ovarian, 23%
      cervical, 23% endometrial, and 6% vulvar. Treatment at index visit was 61%
      chemotherapy, 16% no treatment, 8% recent surgery, and 6% radiation. Mean visits
      was 5.7 (SD 3.9, range 3-28). Most common presenting complaints were
      gastrointestinal and pain. Patients near end of life were more likely to be
      admitted. EDV frequently occurred outside standard work hours (63%).
      EDV/admissions resulted in total variable expenses of $1 462 581 ($982 933 direct
      expense, $479 648 service expense). Interventions to decrease super-utilization
      could target symptom management, off-hour support, patients on chemotherapy, and
      end of life. Approaches could include multidisciplinary resources, palliative
      care teams, extending office hours, and earlier initiation of hospice.

PMID- 29463093
TI  - Utility of DWI with quantitative ADC values in ovarian tumors: a meta-analysis of
      diagnostic test performance.
AB  - Background Diffusion-weighted imaging (DWI) and quantitative apparent diffusion
      coefficient (ADC) values are widely used in the differential diagnosis of ovarian
      tumors. Purpose To assess the diagnostic performance of quantitative ADC values
      in ovarian tumors. Material and Methods PubMed, Embase, the Cochrane Library, and
      local databases were searched for studies assessing ovarian tumors using
      quantitative ADC values. We quantitatively analyzed the diagnostic performances
      for two clinical problems: benign vs. malignant tumors and borderline vs.
      malignant tumors. We evaluated diagnostic performances by the pooled sensitivity
      and specificity values and by summary receiver operating characteristic (SROC)
      curves. Subgroup analyses were used to analyze study heterogeneity. Results From
      the 742 studies identified in the search results, 16 studies met our inclusion
      criteria. A total of ten studies evaluated malignant vs. benign ovarian tumors
      and six studies assessed malignant vs. borderline ovarian tumors. Regarding the
      diagnostic accuracy of quantitative ADC values for distinguishing between
      malignant and benign ovarian tumors, the pooled sensitivity and specificity
      values were 0.91 and 0.91, respectively. The area under the SROC curve (AUC) was
      0.96. For differentiating borderline from malignant tumors, the pooled
      sensitivity and specificity values were 0.89 and 0.79, and the AUC was 0.91. The
      methodological quality of the included studies was moderate. Conclusion
      Quantitative ADC values could serve as useful preoperative markers for predicting
      the nature of ovarian tumors. Nevertheless, prospective trials focused on
      standardized imaging parameters are needed to evaluate the clinical value of
      quantitative ADC values in ovarian tumors.

PMID- 29463094
TI  - Use of personal electronic devices by psychiatric inpatients: benefits, risks and
      attitudes of patients and staff.
AB  - OBJECTIVES: The study aimed to evaluate the attitudes of patients and staff in
      relation to the potential benefits and risks of allowing psychiatric inpatients
      controlled access to personal electronic devices (PEDs), and to document a
      snapshot audit of practice within the mental health inpatient units of New South
      Wales, Australia. METHODS: Psychiatric inpatients and staff at Royal North Shore
      Hospital's Mental Health inpatient units were surveyed, and an audit of the
      policies of the psychiatric inpatients of New South Wales was undertaken.
      RESULTS: Access to PEDs is denied in 85% of New South Wales psychiatric inpatient
      units. While patients and staff appear to concur on the risks of access to PEDs
      and the need for risk assessment and rules, compared to patients, staff appear to
      underestimate the importance of PEDs to maintaining social connection and
      recovery. CONCLUSIONS: This study may assist in the formulation of local policy
      and procedure to allow a more recovery-oriented approach to the question of
      whether patients should have access to their PEDs while in hospital.

PMID- 29463095
TI  - Current and future use of nucleo(s)tide prodrugs in the treatment of hepatitis C
      virus infection.
AB  - This review describes the current state of discovery of past most important
      nucleoside and nucleotide prodrugs in the treatment of hepatitis C virus
      infection as well as future potential drugs currently in discovery or clinical
      evaluation. I highlight first generation landmark prodrug compounds which have
      been the foundations of incremental improvements toward the discovery and
      approval milestone of Sofosbuvir. Sofosbuvir is the first nucleotide prodrug
      marketed for hepatitis C virus treatment and the backbone of current combination
      therapies. Since this approval, new nucleotide prodrugs using the same design of
      Sofosbuvir McGuigan prodrug have emerged, some of them progressing through
      advanced clinical trials and may become available as new incremental alternative
      hepatitis C virus treatments in the future. Although since Sofosbuvir success,
      only minimal design efforts have been invested in finding better liver targeted
      prodrugs, a few novel prodrugs are being studied and their different modes of
      activation may prove beneficial over the heart/liver targeting ratio to reduce
      potential drug-drug interaction in combination therapies and yield safer
      treatment to patients. Prodrugs have long been avoided as much as possible in the
      past by development teams due to their metabolism and kinetic characterization
      complexity, but with their current success in hepatitis C virus treatment, and
      the knowledge gained in this endeavor, should become a first choice in future
      tissue targeting drug discovery programs beyond the particular case of
      nucleos(t)ide analogs.

PMID- 29463096
TI  - Inhibition of Radiation-Induced Ccl2 Signaling Protects Lungs from Vascular
      Dysfunction and Endothelial Cell Loss.
AB  - AIMS: Radiation-induced normal tissue toxicity often precludes the application of
      curative radiation doses. Here we investigated the therapeutic potential of
      chemokine C-C motif ligand 2 (Ccl2) signaling inhibition to protect normal lung
      tissue from radiotherapy (RT)-induced injury. RESULTS: RT-induced vascular
      dysfunction and associated adverse effects can be efficiently antagonized by
      inhibition of Ccl2 signaling using either the selective Ccl2 inhibitor bindarit
      (BIN) or mice deficient for the main Ccl2 receptor CCR2 (KO). BIN-treatment
      efficiently counteracted the RT-induced expression of Ccl2, normalized
      endothelial cell (EC) morphology and vascular function, and limited lung
      inflammation and metastasis early after irradiation (acute effects). A similar
      protection of the vascular compartment was detected by loss of Ccl2 signaling in
      lungs of CCR2-KO mice. Long-term Ccl2 signaling inhibition also significantly
      limited EC loss and accompanied fibrosis progression as adverse late effect. With
      respect to the human situation, we further confirmed that Ccl2 secreted by RT
      induced senescent epithelial cells resulted in the activation of normally
      quiescent but DNA-damaged EC finally leading to EC loss in ex vivo cultured human
      normal lung tissue. INNOVATION: Abrogation of certain aspects of the secretome of
      irradiated resident lung cells, in particular signaling inhibition of the
      senescence-associated secretory phenotype-factor Ccl2 secreted predominantly by
      RT-induced senescent epithelial cells, resulted in protection of the endothelial
      compartment. CONCLUSIONS: Radioprotection of the normal tissue via Ccl2 signaling
      inhibition without simultaneous protection or preferable radiosensitization of
      tumor tissue might improve local tumor control and survival, because higher doses
      of radiation could be used. Antioxid. Redox Signal. 00, 000-000.

PMID- 29463097
TI  - Prevalence and associated factors of Internet gaming disorder among community
      dwelling adults in Macao, China.
AB  - Background and aims Internet gaming disorder (IGD) has been mainly studied among
      adolescents, and no research to date has examined its prevalence in general
      Chinese adult populations. This study estimated the prevalence of probable IGD in
      community-dwelling adults in Macao, China. Associations between IGD and
      psychological distress (i.e., depression and anxiety) as well as IGD and
      character strength (i.e., psychological resilience and purpose in life) were also
      tested. Methods A random, representative sample of 1,000 Chinese residents (44%
      males; mean age = 40.0) was surveyed using a telephone poll design from October
      to November 2016. Results The estimated prevalence of probable IGD was 2.0% of
      the overall sample and 4.3% among the recent gamers (n = 473), with no
      statistically significant sex and age effects observed (p > .05). The two most
      prevalent IGD symptoms were mood modification and continued engagement, despite
      negative consequences. Probable IGD respondents were more vulnerable to
      psychological distress (25.0% and 45.0% for moderate or above levels of
      depression and anxiety, respectively) than their non-IGD counterparts. They also
      reported a lower level of psychological resilience than non-IGD respondents. No
      significant buffering effect of the two character strength variables on the
      distress-IGD relationship was found. Discussion and conclusions These results
      provide empirical evidence that IGD is a mental health threat not only to
      adolescents but also to adults. IGD was significantly associated with
      psychological distress, which should be addressed in conjunction with IGD
      symptoms in interventions. Inclusion of gamers of both sexes and different age
      groups in future prevention programs is also recommended.

PMID- 29463099
TI  - Factors associated with uptake of home-based HIV counselling and testing and HIV
      care services among identified HIV-positive persons in Masaka, Uganda.
AB  - We investigated uptake of home-based HIV counselling and testing (HBHCT) and HIV
      care services post-HBHCT in order to inform the design of future HBHCT
      programmes. We used data from an open-label cluster-randomised controlled trial
      which had demonstrated the effectiveness of a post-HBHCT counselling intervention
      in increasing linkage to HIV care. HBHCT was offered to adults (>=18 years) from
      28 rural communities in Masaka, Uganda; consenting HIV-positive care naive
      individuals were enrolled and referred for care. The trial's primary outcome was
      linkage to HIV care (clinic-verified registration for care) six months post
      HBHCT. Random effects logistic regression was used to investigate factors
      associated with HBHCT uptake, linkage to care, CD4 count receipt, and
      antiretroviral therapy (ART) initiation; all analyses of uptake of post-HBHCT
      services were adjusted for trial arm allocation. Of 13,455 adults offered HBHCT,
      12,100 (89.9%) accepted. HBHCT uptake was higher among men [adjusted odds ratio
      (aOR) 1.20, 95% confidence interval (CI) = 1.07-1.36] than women, and decreased
      with increasing age. Of 551 (4.6%) persons who tested HIV-positive, 205 (37.2%)
      were in care. Of those not in care, 302 (87.3%) were enrolled in the trial and of
      these, 42.1% linked to care, 35.4% received CD4 counts, and 29.8% initiated ART
      at 6 months post-HBHCT. None of the investigated factors was associated with
      linkage to care. CD4 count receipt was lower in individuals who lived >=30 min
      from an HIV clinic (aOR 0.60, 95%CI = 0.34-1.06) versus those who lived closer.
      ART initiation was higher in older individuals (>=45 years versus <25 years, aOR
      2.14, 95% CI = 0.98-4.65), and lower in single (aOR 0.60, 95% CI = 0.28-1.31) or
      divorced/separated/widowed (aOR 0.47, 95% CI = 0.23-0.93) individuals versus
      those married/cohabiting. HBHCT was highly acceptable but uptake of post-HBHCT
      care was low. Other than post-HBHCT counselling, this study did not identify
      specific issues that require addressing to further improve linkage to care.

PMID- 29463098
TI  - Both active and sham low-frequency rTMS single sessions over the right DLPFC
      decrease cue-induced cravings among pathological gamblers seeking treatment: A
      randomized, double-blind, sham-controlled crossover trial.
AB  - Background Craving is a core symptom of addictive disorders, such as pathological
      gambling for example. Over the last decade, several studies have assessed the
      efficacy of repetitive transcranial magnetic stimulation (rTMS) in the addiction
      field, which triggers the dorsolateral prefrontal cortex (DLPFC) to decrease
      craving. The STIMJEU study investigated whether a single session of low-frequency
      (LF, i.e., 1 Hz) rTMS applied to the right DLPFC reduced cue-induced gambling
      craving in a sample of treatment-seeking pathological gamblers. Methods Thirty
      patients received both active and sham rTMS in random order and were blinded to
      the condition in a within-subject crossover design. Outcome measures included
      self-reported gambling craving (Visual Analog Scale and Gambling Craving Scale)
      and physiological measures (heart rate and blood pressure). Results The rTMS
      sessions were associated with a significant decrease in the gambling urge,
      regardless of whether the session was active or sham. When controlling cue
      induced craving levels, no effects were observed on craving for active rTMS.
      Overall, rTMS was well-tolerated, and the credibility of the sham procedure was
      assessed and appeared to be appropriate. Conclusions We failed to demonstrate the
      specific efficacy of one session of LF rTMS to decrease cue-induced craving in
      pathological gamblers. A strong placebo-effect and rTMS parameters may partly
      explain these results. Yet, we are convinced that rTMS remains a promising
      therapeutic method. Further studies are required to examine its potential effect.

PMID- 29463100
TI  - Community treatment orders: towards a new research agenda.
AB  - OBJECTIVES: The aim of this study was to report on a half-day multi-stakeholder
      symposium on community treatment orders (CTOs) hosted by the Melbourne Social
      Equity Institute (MSEI), which identified research gaps and opportunities, and
      produced an agreed agenda for future CTO research. METHODS: The MSEI convened a
      symposium for 22 experts in CTO research to discuss research priorities in this
      field in Australasia. An independent moderator elicited views and recommendations
      and produced a report detailing possible research projects. RESULTS: Research on
      CTOs is contentious and there is a need to gather and examine information
      regarding both their use and utility. Due to the complexities involved, it was
      agreed that research should be undertaken in partnership with persons with had
      lived experience of mental health problems, clinicians, policymakers and other
      interdisciplinary stakeholders. Five key areas for future investigation were
      identified. CONCLUSIONS: The issues and recommendations arising from the
      symposium should shape the scope, nature and conduct of future research
      directions in the field.

PMID- 29463102
TI  - Social and behavioral factors associated with failing second-line ART - results
      from a cohort study at the Themba Lethu Clinic, Johannesburg, South Africa.
AB  - Poor adherence is a main challenge to successful second-line ART in South Africa.
      Studies have shown that patients can re-suppress their viral load following
      intensive adherence counselling. We identify factors associated with failure to
      re-suppress on second-line ART. The study was a retrospective cohort study which
      included HIV-positive adults who experienced an elevated viral load >=400
      copies/ml on second-line ART between January 2013-July 2014, had completed an
      adherence counselling questionnaire and had a repeat viral load result recorded
      within 6 months of intensive adherence counselling. Log-binomial regression was
      used to evaluate the association between patient characteristics and social,
      behavioral or occupational factors and failure to suppress viral load (>=400
      copies/ml). A total of 128 patients were included in the analysis, and of these
      39% (n = 50) failed to re-suppress their viral load. Compared to those who
      suppressed, far more patients who failed to suppress reported living with family
      (44.2% vs. 23.7%), missing a dose in the past week (53.3% vs. 30.0%), using
      traditional/herbal medications (63.2% vs. 34.3%) or had symptoms suggestive of
      depression (57.7% vs. 34.3%). These patient-related factors could be targeted for
      interventions to reduce the risk for treatment failure and prevent switching to
      expensive third-line ART.

PMID- 29463103
TI  - Toward an Integrated Understanding of Retrograde Control of Photosynthesis.
AB  - SIGNIFICANCE: Photosynthesis takes place in the chloroplast of eukaryotes, which
      occupies a large portion of the photosynthetic cell. The chloroplast function and
      integrity depend on intensive material and signal exchange between all genetic
      compartments and conditionally secure efficient photosynthesis and high fitness.
      Recent Advances: During the last two decades, the concept of mutual control of
      plastid performance by extraplastidic anterograde signals acting on the
      chloroplast and the feedback from the chloroplast to the extraplastidic space by
      retrograde signals has been profoundly revised and expanded. It has become clear
      that a complex set of diverse signals is released from the chloroplast and
      exceeds the historically proposed small number of information signals. Thus, it
      is also recognized that redox compounds and reactive oxygen species play a
      decisive role in retrograde signaling. CRITICAL ISSUES: The diversity of
      processes controlled or modulated by the retrograde network covers all molecular
      levels, including RNA fate and translation, and also includes subcellular
      heterogeneity, indirect gating of other organelles' metabolism, and specific
      signaling routes and pathways, previously not considered. All these processes
      must be integrated for optimal adjustment of the chloroplast processes. Thus,
      evidence is presented suggesting that retrograde signaling affects translation,
      stress granule, and processing body (P-body) dynamics. FUTURE DIRECTIONS:
      Redundancy of signal transduction elements, parallelisms of pathways, and
      conditionally alternative mechanisms generate a robust network and system that
      only tentatively can be assessed by use of single-site mutants. Antioxid. Redox
      Signal. 00, 000-000.

PMID- 29463104
TI  - Momordica charantia Inhibits Inflammatory Responses in Murine Macrophages via
      Suppression of TAK1.
AB  - Momordica charantia known as bitter melon is a representative medicinal plant
      reported to exhibit numerous pharmacological activities such as antibacterial,
      antidiabetic, anti-inflammatory, anti-oxidant, antitumor, and hypoglycemic
      actions. Although this plant has high ethnopharmacological value for treating
      inflammatory diseases, the molecular mechanisms by which it inhibits the
      inflammatory response are not fully understood. In this study, we aim to identify
      the anti-inflammatory mechanism of this plant. To this end, we studied the
      effects of its methanol extract (Mc-ME) on lipopolysaccharide (LPS)-stimulated
      RAW264.7 macrophages. Specifically, we evaluated nitric oxide (NO) production,
      mRNA expression of inflammatory genes, luciferase reporter gene activity, and
      putative molecular targets. Mc-ME blocked NO production in a dose-dependent
      manner in RAW264.7 cells; importantly, no cytotoxicity was observed. Moreover,
      the mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase
      (COX)-2 were decreased by Mc-ME treatment in a dose-dependent manner. Luciferase
      assays and nuclear lysate immunoblotting analyses strongly indicated that Mc-ME
      decreases the levels of p65 [a nuclear factor (NF)-[Formula: see text]B subunit]
      and c-Fos [an activator protein (AP)-1 subunit]. Whole lysate immunoblotting
      assays, luciferase assays, and overexpression experiments suggested that
      transforming growth factor [Formula: see text]-activated kinase 1 (TAK1) is
      targeted by Mc-ME, thereby suppressing NF-[Formula: see text]B and AP-1 activity
      via downregulation of extracellular signal-regulated kinases (ERKs) and AKT.
      These results strongly suggest that Mc-ME exerts its anti-inflammatory activity
      by reducing the action of TAK1, which also affects the activation of NF-[Formula:
      see text]B and AP-1.

PMID- 29463101
TI  - Autophagy: A Lysosome-Dependent Process with Implications in Cellular Redox
      Homeostasis and Human Disease.
AB  - SIGNIFICANCE: Autophagy, a lysosome-dependent homeostatic process inherent to
      cells and tissues, has emerging significance in the pathogenesis of human
      disease. This process enables the degradation and turnover of cytoplasmic
      substrates via membrane-dependent sequestration in autophagic vesicles
      (autophagosomes) and subsequent lysosomal delivery of cargo. Recent Advances:
      Selective forms of autophagy can target specific substrates (e.g., organelles,
      protein aggregates, and lipids) for processing. Autophagy is highly regulated by
      oxidative stress, including exposure to altered oxygen tension, by direct and
      indirect mechanisms, and contributes to inducible defenses against oxidative
      stress. Mitochondrial autophagy (mitophagy) plays a critical role in the
      oxidative stress response, through maintenance of mitochondrial integrity.
      CRITICAL ISSUES: Autophagy can impact a number of vital cellular processes
      including inflammation and adaptive immunity, host defense, lipid metabolism and
      storage, mitochondrial homeostasis, and clearance of aggregated proteins, all
      which may be of significance in human disease. Autophagy can exert both
      maladaptive and adaptive roles in disease pathogenesis, which may also be
      influenced by autophagy impairment. This review highlights the essential roles of
      autophagy in human diseases, with a focus on diseases in which oxidative stress
      or inflammation play key roles, including human lung, liver, kidney and heart
      diseases, metabolic diseases, and diseases of the cardiovascular and neural
      systems. FUTURE DIRECTIONS: Investigations that further elucidate the complex
      role of autophagy in the pathogenesis of disease will facilitate targeting this
      pathway for therapies in specific diseases.

PMID- 29463105
TI  - NEET Proteins: A New Link Between Iron Metabolism, Reactive Oxygen Species, and
      Cancer.
AB  - SIGNIFICANCE: Cancer cells accumulate high levels of iron and reactive oxygen
      species (ROS) to promote their high metabolic activity and proliferation rate.
      However, high levels of iron and ROS can also lead to enhanced oxidative stress
      and the activation of cell death pathways such as apoptosis and ferroptosis. This
      has led to the proposal that different drugs that target iron and/or ROS
      metabolism could be used as anticancer drugs. However, due to the complex role
      iron and ROS play in cells, the majority of these drugs yielded mixed results,
      highlighting a critical need to identify new players in the regulation of iron
      and ROS homeostasis in cancer cells. Recent Advances: NEET proteins belong to a
      newly discovered class of iron-sulfur proteins (2Fe-2S) required for the
      regulation of iron and ROS homeostasis in cells. Recent studies revealed that the
      NEET proteins NAF-1 (CISD2) and mitoNEET (CISD1) play a critical role in
      promoting the proliferation of cancer cells, supporting tumor growth and
      metastasis. Moreover, the function of NEET proteins in cancer cells was found to
      be dependent of the degree of lability of their 2Fe-2S clusters. CRITICAL ISSUES:
      NEET proteins could represent a key regulatory link between the maintenance of
      high iron and ROS in cancer cells, the activation of cell death and survival
      pathways, and cellular proliferation. FUTURE DIRECTIONS: Because the function of
      NEET proteins depends on the lability of their clusters, drugs that target the
      2Fe2S clusters of NEET proteins could be used as promising anticancer drugs.
      Antioxid. Redox Signal. 00, 000-000.

PMID- 29463106
TI  - Association of Preprocedural Hyperglycemia With Contrast-Induced Acute Kidney
      Injury and Poor Outcomes After Emergency Percutaneous Coronary Intervention.
AB  - We investigated whether preprocedural hyperglycemia was associated with contrast
      induced acute kidney injury (CI-AKI) and long-term outcomes in patients with
      acute coronary syndrome (ACS) who underwent emergency percutaneous coronary
      intervention (PCI). Patients (n = 558) with ACS who underwent emergency PCI were
      consecutively enrolled. Preprocedural hyperglycemia was defined as glucose levels
      >198 mg/dL (11 mmol/L). The primary outcome was CI-AKI (>=0.3 mg/dL absolute or
      >=50% relative serum creatinine increase 48 hours after contrast medium
      exposure). Overall, 103 (18.5%) patients had preprocedural hyperglycemia and 89
      (15.9%) patients developed CI-AKI. The incidence of CI-AKI was significantly
      higher in patients with hyperglycemia than without (28.2% vs 13.2%; P < .01).
      Multivariate analysis indicated that preprocedural hyperglycemia was an
      independent predictor of CI-AKI (odds ratio = 1.971, 95% confidence interval
      [CI]: 1.129-3.441; P < .05). In addition, preprocedural hyperglycemia was
      associated with an increased risk of all-cause mortality during the 2-year follow
      up (hazard ratio = 2.440, 95% CI: 1.394-4.273; P = .002). Preprocedural
      hyperglycemia is a significant and independent predictor of CI-AKI and long-term
      outcomes.

PMID- 29463107
TI  - Outcomes of a Pharmacist-Managed Heart Failure Medication Titration Assistance
      Clinic.
AB  - BACKGROUND: National guidelines recommend angiotensin-converting enzyme (ACE)
      inhibitors or angiotensin-receptor blockers (ARBs) and beta-blockers (BBs) at
      target doses for morbidity and mortality benefits in heart failure with reduced
      ejection fraction (HFrEF); regardless, titration of these therapies in practice
      remains suboptimal. We implemented an outpatient pharmacist-managed HFrEF
      medication titration assistance clinic (MTAC) at one institution to improve
      titration for general cardiology (GC) patients. OBJECTIVE: To evaluate MTAC
      impact by determining the proportion of patients on target or maximum tolerated
      ACE inhibitor/ARB and BB doses. METHODS: A retrospective chart review of adult
      patients with documented ejection fraction <=40% managed in the MTAC or GC from
      2011 to 2013 was conducted. HFrEF medication regimens were collected at initial
      visit and months 1, 2, 3, 6, 9, and 12 to assess titration. Target doses were
      defined per guideline or dose at which ejection fraction recovered during the
      study. Maximum tolerated doses were defined as the highest dose patients
      tolerated without physiological limitations. RESULTS: Of 148 patients, the MTAC
      managed 51 and GC managed 97. At baseline, 90% of MTAC versus 82% of GC patients
      were prescribed ACE inhibitors/ARBs and BBs. In the MTAC, 4% were at target or
      maximum tolerated doses compared with 32% of GC patients ( P < 0.001). At 12
      months, 95% of patients in the MTAC and 87% in GC were prescribed ACE
      inhibitors/ARBs and BBs. Of those prescribed ACE inhibitors/ARBs and BBs, 64% in
      the MTAC versus 40% in GC reached target or maximum tolerated doses ( P = 0.01).
      CONCLUSIONS: The pharmacist-managed MTAC increased the proportion of patients on
      optimal HFrEF therapies and are a resource for GC patients.

PMID- 29463108
TI  - Coping and care-related stress in parents of a child with autism spectrum
      disorder.
AB  - BACKGROUND AND OBJECTIVES: Parenting a child with Autism Spectrum Disorder (ASD)
      is challenging and can result in elevated levels of parenting stress. This study
      investigated the relationship between parent-ratings of their child's ASD
      symptoms and two conceptually different measures of parenting stress: One
      specific to the ASD context and the other a general stress measure applicable to
      the broader caregiving context. Additionally, the influence of coping style on
      the relationship between child's ASD symptoms and parenting stress was
      investigated. DESIGN AND METHODS: Using an internet survey, parents (N = 178)
      caring for a child with ASD reported on coping strategies, completed two measures
      of parenting stress, and assessed their child's ASD symptoms. RESULTS: Parenting
      stress increased with severity of the child's ASD symptoms, but the strength of
      this relationship depended on whether a general or disorder-specific measure of
      parenting stress was used. Regression analyses indicated that some coping
      strategies moderated the impact of ASD symptom severity on the parent's care
      related stress, but moderation depended on how stress was conceptualized.
      CONCLUSION: This study reinforces the importance of identifying the coping
      strategies of parents of children with developmental disorders, and highlights
      the consequences of using different conceptual approaches to measure parenting
      stress.

PMID- 29463109
TI  - Survey of the effect of doxorubicin and flavonoid extract of white Morus alba
      leaf on apoptosis induction in a-172 GBM cell line.
AB  - In this study, the effect of doxorubicin, flavonoid extract of white Morus alba
      leaf (MFE) and a combination of doxorubicin and flavonoid extract on Bax and Bcl2
      levels and caspase 3 activity of cancer A-172 GBM cell line was investigated.
      Bax/Bcl2 levels of treated A-172 GBM cell line with flavonoid extract of white
      mulberry leaf were estimated by ELISA methods. Caspase 3 activity of treated A
      172 GBM cells was determined by calorimetric assay. The flow cytometry assessment
      was used to estimate the apoptosis percent of treated A-172 GBM cells. Treatment
      of A-172 GBM cells with MFE, doxorubicin and a combination of MFE and doxorubicin
      caused a significant decrease in Bcl2 level and an increase in Bax level. The
      apoptosis percent of treated cells were also elevated significantly. Present
      results suggest that concomitant use of herbal medicine and chemotherapy may be
      an effective alternative method for the treatment of cancers.

PMID- 29463110
TI  - The importance of the therapeutic relationship when providing information to
      parents of children with long-term disabilities: The views and experiences of UK
      paediatric therapists.
AB  - The purpose of this study was to understand the views and experiences of
      paediatric therapists working in the United Kingdom regarding the importance of
      the therapeutic relationship when providing information for parents of children
      with long-term disabilities. The aim was to develop new perspectives, to
      encourage dialogue and reflection for change and to identify practical
      suggestions for health professionals when developing therapeutic relationships.
      This study employed an interpretive phenomenological methodology. Semi
      structured, in-depth interviews were carried out with seven health professionals
      from a single National Health Service trust in the United Kingdom (children's
      physiotherapists, occupational therapists and speech therapists). Resultant data
      were analysed using a systematic process of thematic content analysis. One main
      theme 'The Importance of the Therapeutic Relationship: Balancing a Positive
      Relationship with Professional Responsibility' is presented and discussed.
      Paediatric therapists recognize that fostering a positive therapeutic
      relationship is vital to facilitate parental engagement with the information they
      provide. Despite this it was felt that efforts to maintain a positive
      relationship needed to be carefully balanced with discharging professional
      responsibility to the child. A preliminary model 'The Therapeutic Relationship
      Continuum' is presented, aiming to help health professionals self-assess and
      reflect on the dynamic interface between the therapeutic relationship and
      information provision.

PMID- 29463111
TI  - An ancient remedial repurposing: synthesis of new pinocembrin fatty acid acyl
      derivatives as potential antimicrobial/anti-inflammatory agents.
AB  - Five new pinocembrin derivatives (MC1-MC5) were synthesized by Steglich reaction,
      and investigated for their antimicrobial, antioxidant, and anti-inflammatory
      activity. MC2 (oleoyl derivative) and MC3 (linoleoyl derivative) have shown the
      highest inhibitory effects on bacterial proliferation, with MIC values of 32
      MUg/mL against Staphylococcus aureus. The docosahexaenoyl derivative MC5
      displayed the highest anti-inflammatory activity, decreasing NO production in LPS
      stimulated macrophages with an IC50 value of 15.51 MUg/mL higher than the
      positive control diclofenac (IC50 of 39.71 MUg/mL). All new synthesized compounds
      showed no anti-proliferative effects on RAW 264.7 cells. Results demonstrated as
      the introduction of fatty acid substituents improved the biological profile of
      pinocembrin. Moreover, the chemical nature of substituents significantly affects
      the bioactivity. These preliminary results outline the importance to investigate
      the synthesis of pinocembrin fatty acids derivatives as new and safe anti
      microbial/anti-inflammatory agents.

PMID- 29463112
TI  - Prevalence of obesity and diabetes in the socioeconomic transition of rural Mayas
      of Yucatan from 1962 to 2000.
AB  - BACKGROUND: The Mayas of the State of Yucatan in Mexico are the only aboriginal
      group with obesity and diabetes data before 1997. OBJECTIVE: To analyze
      socioeconomic trends associated with the increase in obesity and diabetes seen in
      rural Yucatan from 1962 to 2000. METHODS: Body weight, height and venous Fasting
      Blood Glucose (FBG) were measured in 263 rural Maya adults participating in a
      2000 nutrition survey. RESULTS: Diabetes (FBG > 125 mg/dL) and obesity (BMI >= 30
      kg/m2) were 10.6% and 35.7%, respectively. These results contrast with those of a
      1962 survey where diabetic prevalence was 2.3% and 0% in women and men
      respectively, with widespread adult pellagra and malnutrition. An important
      socioeconomic transition that took place in Yucatan during this lapse appeared to
      be associated to the obesity and diabetes increase. CONCLUSIONS: Rural Yucatan
      evolved from malnutrition conditions to high prevalence of obesity and diabetes
      in less than 40 years. This change was associated with the transition from an
      agroindustry-based economy, characterized by high-energy expenditure and low
      protein intake, to lower energy requirements of a Government-subsidized economy
      with larger food supply.

PMID- 29463113
TI  - Pediatric Lip Adhesion Following Bullous Erythema Multiforme and Review of
      Similar Oral Complications.
AB  - BACKGROUND: Erythema multiforme (EM) is a mucocutaneous disease most often
      associated with preceding herpes simplex virus or Mycoplasma pneumoniae
      infection. It is characterized by targetoid lesions occurring on the limbs and
      head and neck. Mucosal involvement can be extensive. OBJECTIVE: We report a case
      of lip adhesion as a complication of EM in a child who required corrective
      surgery and review similar oral commissure complications. METHODS: We completed a
      review of the literature for similar cases using PubMed and Medline. CONCLUSIONS
      AND RELEVANCE: We present the youngest report of lip adhesion due to striking
      mucositis related to EM. Sequelae of erythema multiforme can be significant, in
      our case requiring surgery. Meticulous oral hygiene should be encouraged when
      mucosal lesions are identified.

PMID- 29463114
TI  - A Case Report Highlighting the Effective Treatment of Alopecia Universalis With
      Tofacitinib in an Adolescent and Adult Patient.

PMID- 29463115
TI  - Evaluation of comparative effectiveness research: a practical tool.
AB  - Comparative effectiveness research (CER) guidelines have been developed to direct
      the field toward the most rigorous study methodologies. A challenge, however, is
      how to ensure the best evidence is generated, and how to translate
      methodologically complex or nuanced CER findings into usable medical evidence. To
      reach that goal, it is important that both researchers and end users of CER
      output become knowledgeable about the elements that impact the quality and
      interpretability of CER. This paper distilled guidance on CER into a practical
      tool to assist both researchers and nonexperts with the critical review and
      interpretation of CER, with a focus on issues particularly relevant to CER in
      oncology.

PMID- 29463116
TI  - A colonoscopy preparation gone wrong: propylene glycol mistaken for polyethylene
      glycol.

PMID- 29463117
TI  - Micro-Dystrophin Gene Therapy Goes Systemic in Duchenne Muscular Dystrophy
      Patients.
AB  - Whole-body systemic gene therapy is likely the most effective way to reduce
      greatly the disease burden of Duchenne muscular dystrophy (DMD), an X-linked
      inherited muscle disease that leads to premature death in early adulthood.
      Genetically, DMD is due to null mutation of the dystrophin gene, one of the
      largest genes in the genome. Recent studies have shown highly promising
      improvements in animal models with intravascular delivery of the engineered micro
      dystrophin gene by adeno-associated virus (AAV). Several human trials are now
      started to advance AAV micro-dystrophin therapy to DMD patients. This is a
      historical moment for the entire field. Results from these trials will shape the
      future of neuromuscular disease gene therapy.

PMID- 29463118
TI  - Clinical contribution of myositis-related antibodies detected by immunoblot to
      idiopathic inflammatory myositis: A one-year retrospective study.
AB  - In this study, we aimed at evaluating the contribution of an extended myositis
      related antibodies (Abs) determination by immunoblot to the diagnosis,
      classification, and prognosis of idiopathic inflammatory myositis (IIM). Medical
      records of all the patients (n = 237) with myositis-related Ab requests addressed
      to our department over a one-year period were retrospectively analyzed. Patients
      were classified as IIM, auto-immune disease (AID) other than IIM, and other
      diagnosis, and examined for their Ab profiles as determined by immunoblot. Ab
      positivity was qualified semi-quantitatively as low or strong according to the
      manufacturer's recommendations. Among the 45 Ab-positive patients, 49% were
      diagnosed an IIM, 22% another AID, and 29% another diagnosis. The clinico
      serological patterns of the myositis-related Ab+ patients fully recapitulated
      those described in the literature. Among non-IIM patients, anti-PM-Scl was the
      most frequently detected Ab (38%), followed by anti-Mi-2 (15%), and anti-OJ
      (12%). Importantly, strong Ab positivity was significantly more detected in IIM
      vs. non-IIM patients (82% vs. 35%; p = .002). This difference was further
      increased when comparing MSAs only (95% vs. 36%; p = .0004). Accordingly, strong
      Ab positivity associated with high specificity (96%) and positive likelihood
      ratio (pLR =12) for IIM. Our data suggest that while myositis-related Ab,
      including MSA, can be detected by immunoblot in non-IIM patients, strong
      positivity is nevertheless highly predictive of IIM. In conclusion, this work
      suggests that relevant clinical contribution to IIM is provided by the immunoblot
      determination of myositis-related Ab, more especially when considering strong
      positive detection of MSA.

PMID- 29463119
TI  - Effects of Exposure to the Communities That Care Prevention System on Youth
      Problem Behaviors in a Community-Randomized Trial: Employing an Inverse
      Probability Weighting Approach.
AB  - Earlier intention-to-treat (ITT) findings from a community-randomized trial
      demonstrated effects of the Communities That Care (CTC) prevention system on
      reducing problem behaviors among youth. In ITT analyses, youth were analyzed
      according to their original study community's randomized condition even if they
      moved away from the community over the course of follow-up and received little to
      no exposure to intervention activities. Using inverse probability weights (IPWs),
      this study estimated effects of CTC in the same randomized trial among youth who
      remained in their original study communities throughout follow-up. Data were from
      the Community Youth Development Study, a community-randomized trial of 24 small
      towns in the United States. A cohort of 4,407 youth was followed from fifth grade
      (prior to CTC implementation) to eighth grade. IPWs for one's own moving status
      were calculated using fifth- and sixth-grade covariates. Results from inverse
      probability weighted multilevel models indicated larger effects for youth who
      remained in their study community for the first 2 years of CTC intervention
      implementation compared to ITT estimates. These effects included reduced
      likelihood of alcohol use, binge drinking, smokeless tobacco use, and delinquent
      behavior. These findings strengthen support for CTC as an efficacious system for
      preventing youth problem behaviors.

PMID- 29463120
TI  - Innovations for Evaluation Research: Multiform Protocols, Visual Analog Scaling,
      and the Retrospective Pretest-Posttest Design.
AB  - In this article, we review three innovative methods: multiform protocols, visual
      analog scaling, and the retrospective pretest-posttest design that can be used in
      evaluation research. These three techniques have been proposed for decades, but
      unfortunately, they are still not utilized readily in evaluation research. Our
      goal is to familiarize researchers with these underutilized research techniques
      that could reduce personnel effort and costs for data collection while producing
      better inferences for a study. We begin by discussing their applications and
      special unique features. We then discuss each technique's strengths and
      limitations and offer practical tips on how to better implement these methods in
      evaluation research. We then showcase two recent empirical studies that implement
      these methods in real-world evaluation research applications.

PMID- 29463121
TI  - Assessment of Factors Influencing Communication in Clinical Pharmacy.
AB  - This study aimed to identify and assess the factors that influence communication
      quality between clinical pharmacists and patients using a structural equation
      model based on the predisposing, reinforcing, and enabling constructs in
      educational/environmental diagnosis and evaluation-policy, regulatory, and
      organizational constructs in educational and ecological development model to
      identify the most effective path to increase their communication quality. A
      survey was conducted at 253 Class-A tertiary hospitals in China from March to
      December 2016. During on-site observations, verbal communications between
      clinical pharmacists ( n = 752) and patients were audio recorded, and
      communication quality was rated by an expert panel on an 8-item Quality of
      Communication Rating Scale. Clinical pharmacists completed questionnaires that
      examined the predisposing, enabling, and reinforcing factors that influenced
      communication quality. Finally, AMOS was employed to examine the relationships
      between the three factors and communication quality. The results indicated that
      all three factors positively affected communication quality, with correlation
      coefficients of .26, .13, and .17, respectively. The most influential
      predisposing factor was attitude (.77), the most influential enabling factors
      were self-efficacy (.71) and confidence (.72), and the most influential
      reinforcing factor was rewards (.74). The findings suggest that pharmacists'
      attitudes toward, perceived knowledge of, and skill and confidence in
      communication, and the rewards offered by pharmacy management are the most
      influential factors that influence communication quality.

PMID- 29463122
TI  - Evaluation and Comparison of Contemporary Energy-Based Surgical Vessel Sealing
      Devices.
AB  - INTRODUCTION: We evaluated and compared five currently available energy-based
      vessel sealing devices to assess typical surgical metrics. METHODS: We tested
      Caiman 5 (C5), Harmonic Scalpel Ace Plus (HA), Harmonic Ace +7 (HA7), LigaSure
      (LS), and Enseal G2 (ES) on small (2-5 mm), medium (5.1-7 mm), and large (7.1-9
      mm) vessels obtained from 15 Yorkshire pigs. Vessels were randomly sealed and
      transected. We recorded sealing and transection time, charring and carbonization,
      thermal spread, and bursting pressure (BP). Specimens were sent for
      histopathologic evaluation of seal quality and thermal spread. RESULTS: A total
      of 246 vessels were evaluated: 125 were arteries and 121 were veins. There was no
      difference in BPs for small size arteries. For medium arteries, C5 provided the
      highest BP (proximal and distal jaw), followed by HA7, ES, LS, and HA [1740,
      1600, 1165, 1165, 981, and 571 mm Hg, respectively, HA<C5-D(<0.001); HA<C5
      P(<0.001); HA<ES(0.002); HA<HA7(0.002); HA7<C5-P(0.026); ES<C5-P(0.026); LS<C5
      P(0.001); LS<C5-D(0.014)]. For large arteries, C5 and LS provided highest BP
      followed by HA7, ES, and HA [1676, 530, 467, 467, and 254 mm Hg, respectively,
      C5<HA(<0.001); C5<HA7(0.006); C5<ES(0.006); C5<LS(0.012)]. There were no bursting
      pressure failures for C5, HA7, and LS up to 9 mm vessels. For medium and large
      size arteries, HA had bursting failure of 20% and 40%, respectively. The ES was
      significantly less efficient with small, medium, and large arteries with bursting
      failure rates of 10%, 40%, and 80%, respectively. CONCLUSIONS: In this study, C5
      outperformed all other devices. However, all of the devices provide a seal that
      was superphysiologic in that all burst pressures were >250 mm Hg.

PMID- 29463124
TI  - Designed construction of tween 60@2beta-CD self-assembly vesicles as drug
      delivery carrier for cancer chemotherapy.
AB  - We report a simple strategy to prepare Tween 60@2beta-CD self-assembly vesicles
      in aqueous solution as a new drug delivery carrier for cancer chemotherapy. The
      spherical shape of vesicles was confirmed by transmission electron microscopy
      (TEM) and mean particle sizes were about 33.7 nm, as measured by dynamic light
      scattering, micro-IR results indicated that the self-assembly vesicles was driven
      by hydrogen bonding. Hydrophilic doxorubicin (DOX) was successfully loaded into
      the self-assembly vesicles with drug loading content of 7.85% and loading
      efficiency of 42%. In addition, an in vitro cytotoxicity study and cellular
      uptake assays demonstrated that the DOX-loaded Tween 60@2beta-CD vesicles
      markedly enhanced the cellular uptake and cytotoxicity of DOX toward the Hela
      cells. Furthermore, when used to evaluate the in vivo therapeutic efficacy in
      mice bearing the breast cell line (4T1), DOX-loaded vesicles exhibited superior
      inhibition of tumor growth compared with the DOX solutions.

PMID- 29463123
TI  - Novel application of pluronic lecithin organogels (PLOs) for local delivery of
      synergistic combination of docetaxel and cisplatin to improve therapeutic
      efficacy against ovarian cancer.
AB  - The synergistic combination of docetaxel (DTX) and cisplatin (CIS) by local drug
      delivery with a pluronic lecithin organogel (PLO) to facilitate high drug
      concentrations at tumor sites and less nonspecific distribution to normal organs
      is thought to be beneficial in chemotherapy. In this study, using Capryol-90
      (C90) with the addition of lecithin as the oil phase was developed to carry DTX,
      which was then incorporated into a PLO-containing CIS to formulate a dual-drug
      injectable PLO for local delivery. An optimal PLO composite, P13L0.15O1.5,
      composed of PF127:lecithin:C90 at a 13:0.15:1.5 weight ratio was obtained. The
      sol-gel transition temperature of P13L0.15O1.5 was found to be 33  degrees C.
      Tumor inhibition studies illustrated that DTX/CIS-loaded P13L0.15O1.5 could
      efficiently suppress tumor growth by both intratumoral and peritumoral injections
      in SKOV-3 xenograft mouse model. Pharmacokinetic studies showed that subcutaneous
      administration of P13L0.15O1.5 was able to sustain the release of DTX and CIS
      leading to their slow absorption into the systemic circulation resulting in lower
      area under the plasma concentration curve at 0-72 h (AUC0-72) and maximum
      concentration (Cmax) values but longer half-life (T1/2) and mean residence time
      (MRT) values. An in vivo biodistribution study showed lower DTX and CIS
      concentrations in organs compared to other treatment groups after IT
      administration of the dual drug-loaded P13L0.15O1.5. It was concluded that the
      local co-delivery of DTX and CIS by PLOs may be a promising and effective
      platform for local anticancer drug delivery with minimal systemic toxicities.

PMID- 29463125
TI  - Salbutamol in acute organophosphorus insecticide poisoning - a pilotdose-response
      phase II study.
AB  - BACKGROUND: Treatment of acute organophosphorus (OP) insecticide poisoning is
      difficult, with many patients dying despite best care. Pre-clinical studies have
      shown benefit from salbutamol, possibly due speeding alveolar fluid clearance or
      reducing bronchoconstriction. In this small pilot dose-response study, we aimed
      to explore whether addition of nebulized salbutamol to standard care might
      improve resuscitation. METHODS: We performed a single-blind phase II study
      comparing the effect of two different doses of nebulized salbutamol versus saline
      placebo, in addition to standard treatment. Primary outcome was oxygen
      saturations over the first 60 min of resuscitation; secondary outcomes included
      heart rate, incidence of dysrhythmias, time to 'atropinization', atropine dose
      required, and mortality. RESULT: Seventy-five patients were randomized to receive
      5 mg (Salb5, n = 25) or 2.5mg (Salb2.5, n = 25) of salbutamol, or saline placebo
      (NoSalb, n = 25), by nebulizer. Oxygen saturations did not differ between groups
      over the first 60 min of resuscitation (median AUC NoSalb: 1376 [95% CI 1282 to
      1470], Salb2.5: 1395 [1305 to 1486], Salb5: 1233 [1100 to 1367]; p = .9898).
      Heart rate was also similar across the three arms. Median time to full
      atropinization, and atropine dose required, were the same for all three arms
      (NoSalb 15.0 [10-16] min and 12.6 [8.0-13.4] mg, Salb2.5 15.0 [10-16] min and
      12.6 [9.3-16.8] mg, and Salb5 15.0 [10-20] min and 12.6 [10.7-20.6] mg; p = .4805
      and p = .1871, respectively). Three (12%) patients died in the Salb2.5 and Salb5
      groups and two (8%) in the NoSalb group. CONCLUSION: This pilot study, within the
      limitations of its small size and variation between patients, found no apparent
      evidence that administration of nebulized salbutamol improved resuscitation of
      patients with acute OP insecticide self-poisoning. The data obtained provides a
      basis to design further studies to ultimately test the role of salbutamol in OP
      insecticide poisoning.

PMID- 29463126
TI  - Comparative Study of Internal Fixation of the Ulna and Distal Ulna Resection in
      Patients Older Than 70 Years With Distal Radius and Distal Metaphyseal Ulna
      Fractures.
AB  - BACKGROUND: Acute management of fractures of the distal ulna that are associated
      with fractures of the distal radius remains difficult, particularly in the
      elderly. METHODS: In this study, we investigated whether internal fixation of the
      distal ulna is associated with a higher rate of complications than resection of
      the distal ulna in patients older than 70 years. Twenty-four consecutive patients
      were included in this study, 12 of whom had undergone open reduction and internal
      fixation (ORIF) of the distal ulna, and 12 who had undergone distal ulna
      resection. Patients were retrospectively assessed for range of motion, grip
      strength, pain, and radiographic appearance. The functional outcome was evaluated
      by the Mayo Wrist Score. Complications were classified according to the
      Classification of Surgical Complications. RESULTS: There were no differences in
      patient demographics between the 2 groups, except patient age. Clinical
      evaluation showed no difference at follow-up; however, there were significantly
      more complications associated with ORIF compared with resection. CONCLUSIONS: The
      results from our study show that women older than 70 years with fracture of the
      distal radius and distal ulna have a higher rate of complications if ORIF of the
      distal ulna is performed. Patients should be warned, by surgeons, of this in
      cases where ORIF of the distal ulna is suggested.

PMID- 29463127
TI  - Tin Ring Splint Treatment for Osteoarthritis of the Distal Interphalangeal
      Joints.
AB  - BACKGROUND: We made a tin ring splint for osteoarthritis of the distal
      interphalangeal joint that looks attractive and is easy to wear. We report the
      treatment results with this splint. METHODS: We enrolled 30 patients with painful
      osteoarthritis of the distal interphalangeal joint in this study. A tin ring
      splint was made with tin alloy containing small quantities of silver. Patients
      were instructed to wear the splint when they felt pain. Patients were assessed
      before splint use and after 1, 3, and 6 months of splint use. Endpoints included
      the numeric pain scale, active arc of motion of the distal interphalangeal joint,
      Hand 20, functional assessment criteria of the upper extremities, and treatment
      satisfaction. In addition, data were collected on time to symptom relief and
      satisfaction related to usability and appearance of the splint (0 = dissatisfied,
      10 = satisfied). RESULTS: The numeric pain scale showed significant pain
      improvement from 58.4 +/- 4.1 at baseline to 33.1 +/- 4.5 at 1 month, and the
      Hand 20 score also showed significant improvement from 35.0 +/- 4.3 at baseline
      to 20.2 +/- 3.2 after 6 months. Active arc of motion were not changed
      significantly. Most patients responded that symptoms were relieved by the 10th
      day after treatment. Satisfaction related to usability was 8.9 +/- 0.3, and
      appearance was 7.6 +/- 0.4. CONCLUSIONS: A tin ring splint quickly reduced pain,
      and satisfaction related to usability and appearance was high. This splint could
      be one choice for conservative treatment of osteoarthritis of the distal
      interphalangeal joint.

PMID- 29463128
TI  - Distal Scaphoid Excision in Treatment of Symptomatic Scaphoid Nonunion:
      Systematic Review and Meta-analysis.
AB  - BACKGROUND: Current treatment options for persistent scaphoid nonunion are
      limited to salvage procedures such as proximal row carpectomy (PRC) or 4-corner
      fusion (4CF). Several small studies have demonstrated that distal scaphoid
      excision may provide a simpler alternative with faster recovery. The purpose of
      this study was to determine the efficacy of distal scaphoid excision as a
      treatment option for symptomatic scaphoid nonunion. METHODS: The MEDLINE and
      PubMed databases were searched for the use of distal scaphoid excision in
      scaphoid nonunions. Studies included reported on either the functional or patient
      centered outcomes following distal scaphoid excision for symptomatic scaphoid
      nonunion. RESULTS: Six articles described the outcomes of 70 patients with an
      average of 11.7 patients per study. Functional outcomes including flexion
      extension arc, radial-ulnar deviation, and grip strength improved by an average
      of 98.95%, 58.96%, and 131.08%, respectively. Patient-derived outcomes included
      the Modified Mayo Wrist Score, which improved by 92.6%, and the Disabilities of
      the Arm, Shoulder and Hand, which improved by 137.17%. An average of 68.75% of
      patients experience complete relief of pain with 20.83% of patients experiencing
      pain with strenuous activity. The average postoperative visual analog scale (0
      10) was 0.71. On average, 93.33% of patients returned to work with an average
      time of return being 6.89 weeks. Complete satisfaction was reported by 87.80% of
      patients. Complications included progression into 4CF or PRC and newly developed
      midcarpal arthritis. CONCLUSIONS: Given favorable outcomes, our analysis suggests
      that distal scaphoid excision may be a favorable, low-risk treatment for scaphoid
      nonunion without eliminating more extensive options such as 4CF and wrist
      arthrodesis.

PMID- 29463129
TI  - Antifungal activity of Annona coriacea Mart. ethanol extracts against the
      aetiological agents of cryptococcosis.
AB  - Cryptococcosis is an opportunistic disease with a worldwide distribution. This
      disease is caused by fungi of the genus Cryptococcus, and its treatment is
      limited to several antifungals. In this study, the antifungal, cytotoxic and
      mutagenic properties of ethanol extracts from the bark and leaves of Annona
      coriacea were evaluated against the standard Cryptococcus species and clinical
      yeast specimens. Both extracts of A. coriacea showed inhibitory activity of 1.5
      mg/mL for all of the yeasts tested. The number of viable cells at the lowest
      tested concentration was 0.187 mg/mL. The extracts that were tested showed
      inhibitory activity and reduced the fungal growth of the Cryptococcus gattii
      species and Cryptococcus neoformans species complexes, suggesting that this plant
      may be an effective alternative treatment for cryptococcosis.

PMID- 29463130
TI  - Correction to: Zeinali et al., Cystic dilation of a ventriculus terminalis. Case
      report and review of the literature.

PMID- 29463131
TI  - Rational design for cervical cancer therapeutics: cellular and non-cellular based
      strategies on the horizon for recurrent, metastatic or refractory cervical
      cancer.
AB  - INTRODUCTION: Though cervical cytology, HPV DNA testing, and pre-invasive disease
      management has significantly reduced the number of new diagnoses of cervical
      cancer, women with persistent oncogenic HPV infection are at significant risk for
      developing invasive cervical cancer. Early stage and locally advanced disease can
      be cured, but women with advanced or recurrent disease have a very poor
      prognosis. This underscores the need for different treatment strategies for
      advanced cervical cancer, the most promising of which are novel therapeutics that
      target the ability of HPV to overcome host immune tolerance. Areas covered: This
      review includes new therapies being investigated for the treatment of recurrent,
      metastatic or refractory cervical cancer, separated into broad categories of
      cellular and non-cellular based strategies. Expert opinion: Advanced and
      recurrent cervical cancer has a poor prognosis, prompting investigations into the
      development of strategies that will eradicate tumor and/or overcome host
      immunologic tolerance of disease. It is unknown whether it will be these
      strategies alone or a combination of treatment modalities that will ultimately
      provide the best outcomes; nevertheless, the new data are promising.

PMID- 29463132
TI  - Long-term metabolic cage housing increases anxiety/depression-related behaviours
      in adult male rats.
AB  - There are several reports on unfavourable effects of metabolic cage housing on
      animal welfare mainly due to the characteristic structures of these cages such as
      single housing and grid flooring. This study was aimed to compare the effects of
      long-term metabolic cage housing and conventional housing (normal grouped housing
      in standard cages) on the anxiety/depression-like behaviours in male rats.
      Anxiety/depression-related behaviours were evaluated by use of forced swimming
      test and open field test. Swimming and climbing were significantly lower and
      immobility duration higher in the metabolic cage group. In the open field test,
      total distance, mean velocity, time spent in the central area, zone transition,
      grooming, and rearing scores were significantly lower in the metabolic cage.
      Moreover, serum corticosterone level was higher in the metabolic cage group. The
      results of the study indicate that long-term metabolic cage housing may cause an
      increase in the anxiety- and depression-related behaviours in male rats.

PMID- 29463133
TI  - Effects of combined therapy with resveratrol, continuous and interval exercises
      on apoptosis, oxidative stress, and inflammatory biomarkers in the liver of old
      rats with non-alcoholic fatty liver disease.
AB  - CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic
      liver disorder. OBJECTIVE: Effects of combined therapy with resveratrol, interval
      and continuous exercises on oxidative stress, inflammation, and apoptosis in the
      liver of rats with NAFLD. METHODS: NAFLD rats were organised in patient, saline,
      resveratrol (RSV), continuous exercise, interval exercise, continuous exercise +
      RSV, and interval exercise + RSV groups. RESULTS: Resveratrol supplementation
      alone or in combination with interval and continuous training significantly
      decreased malondialdehyde and TNF-alpha level (p < .05), while the levels of
      catalase; superoxide dismutase and IL-10 were significantly increased (p < .05).
      Although RSV alone significantly decreased the percentage of apoptotic cells
      (17.12%), its combination with interval (10.74%), and continuous (14.85%)
      exercise training demonstrated higher anti-apoptotic activity (p < .05).
      CONCLUSIONS: Although resveratrol alone has an antioxidant, anti-apoptotic and
      anti-inflammatory properties, combined therapy with interval, and continuous
      training can be more effective to mitigate these abnormalities in NAFLD patients.

PMID- 29463134
TI  - Simultaneous bilateral visual auras. A case report.

PMID- 29463135
TI  - Investigating a theatre-based intervention for Indigenous youth with fetal
      alcohol spectrum disorder: Exploration d'une intervention basee sur le theatre
      aupres de jeunes Autochtones atteints du syndrome d'alcoolisme foetal.
AB  - BACKGROUND: Theatre-based interventions use artistic media to facilitate social
      and emotional awareness and have therapeutic benefits for persons with
      developmental disabilities and mental health problems. The role of these
      interventions with Indigenous youth who have emotional, behavioural, and
      cognitive sequelae related to fetal alcohol spectrum disorder (FASD) has not been
      explored. PURPOSE: The purpose of this study was to explore the experiences and
      acceptability of a theatre-based approach for facilitating social communication
      and engagement in youth with FASD. METHOD: Participants were three Indigenous
      youth with FASD. A qualitative exploration of the experiences and acceptability
      of the intervention was conducted via focus groups held 2 weeks post-program
      participation with the participants, their caregivers, and program facilitators.
      The transcripts were analyzed using an inductive thematic approach. FINDINGS: Our
      results identified perceived postintervention improvements in participants'
      development of self-esteem, social skills, and emotional awareness. IMPLICATIONS:
      A theatre-based arts intervention has the potential to support improvements in
      social skills for youth with FASD.

PMID- 29463136
TI  - In Vitro Analysis of Cartilage Regeneration Using a Collagen Type I Hydrogel
      (CaReS) in the Bovine Cartilage Punch Model.
AB  - Objective Limitations of matrix-assisted autologous chondrocyte implantation to
      regenerate functional hyaline cartilage demand a better understanding of the
      underlying cellular/molecular processes. Thus, the regenerative capacity of a
      clinically approved hydrogel collagen type I implant was tested in a standardized
      bovine cartilage punch model. Methods Cartilage rings (outer diameter 6 mm; inner
      defect diameter 2 mm) were prepared from the bovine trochlear groove. Collagen
      implants (+/- bovine chondrocytes) were placed inside the cartilage rings and
      cultured up to 12 weeks. Cartilage-implant constructs were analyzed by histology
      (hematoxylin/eosin; safranin O), immunohistology (aggrecan, collagens 1 and 2),
      and for protein content, RNA expression, and implant push-out force. Results
      Cartilage-implant constructs revealed vital morphology, preserved matrix
      integrity throughout culture, progressive, but slight proteoglycan loss from the
      "host" cartilage or its surface and decreasing proteoglycan release into the
      culture supernatant. In contrast, collagen 2 and 1 content of cartilage and
      cartilage-implant interface was approximately constant over time. Cell-free and
      cell-loaded implants showed (1) cell migration onto/into the implant, (2)
      progressive deposition of aggrecan and constant levels of collagens 1 and 2, (3)
      progressively increased mRNA levels for aggrecan and collagen 2, and (4)
      significantly augmented push-out forces over time. Cell-loaded implants displayed
      a significantly earlier and more long-lasting deposition of aggrecan, as well as
      tendentially higher push-out forces. Conclusion Preserved tissue integrity and
      progressively increasing cartilage differentiation and push-out forces for up to
      12 weeks of cultivation suggest initial cartilage regeneration and lateral
      bonding of the implant in this in vitro model for cartilage replacement
      materials.

PMID- 29463137
TI  - Evaluation of the body mass index (BMI) in children born to organ transplant
      recipients.
AB  - BACKGROUND: Overweight and obesity are one of the most serious clinical health
      problems. Until now, the long-term development of children born to mothers after
      transplantation is unknown. In this study, we attempted to present the analysis
      of the prevalence of overweight in the population of mothers after kidney or
      liver transplants. METHODS: A comparison of body mass index (BMI) measurements
      performed in 61 children of kidney transplant women (study group) and 64 children
      born to healthy mothers (control group). The children from both groups were born
      at a similar gestational age and in the similar time period from 12/1996 to
      11/2010. BMI was measured once on one of the follow-up visits in the time period
      from 07/2010 to 11/2013. BMI was assessed in infants older than one month as well
      as in toddlers or children in the preschool or school age. The results obtained
      in the study group of children born to transplanted mothers were compared with
      control group results and with the theoretical population data. RESULTS: There
      were no differences in the incidence of underweight and overweight, when BMI
      values of children born to transplanted mothers were compared to those of
      children of healthy mothers. There was a trend towards a greater incidence of
      obesity in children of studied group compared to controls (16 versus 6%, p =
      .072). Among analysed factors, it was noted that prenatal exposure to tacrolimus
      was associated with a 2.8-fold increased risk of developing a higher BMI in later
      follow-up. CONCLUSIONS: Obesity among children of mothers after kidney or liver
      transplants seems to be more frequently observed. This observation may be an
      important factor in the further paediatric care, especially in children born to
      transplanted mothers treated chronically with tacrolimus.

PMID- 29463138
TI  - Prenatal diagnosis of intra hepatic arterio venous fistula: case report and
      review of the literature.
AB  - AIM: To describe the prenatal features and management of a congenital intra
      hepatic fistula. MATERIAL AND METHODS: Case report Results: Congenital intra
      hepatic fistula are extremely rare. The prenatal ultrasound seiology is
      described. CONCLUSION: Prenatal diagnosis of these anomalies may improve pre and
      post natal management.

PMID- 29463139
TI  - Non-persistent pesticides in breast milk in an agricultural area in Turkey.
AB  - BACKGROUND: Organophosphates, pythyreoids, carbamate pesticides and fungicides
      are heavily used in agriculture. They may have dangerous effects on newborn
      health especially on immune system and growth via prenatal transmission by
      placenta or postnatal transmission by breastfeeding. METHODS: In 2015, 144 non
      persistent pesticides in 64 milk samples of 32 mothers were studied by OuEChERS
      method in liquid chromatography/tandem mass spectrometer in neonatal Intensive
      Care Unit in Adana, a city in Cukurova region which is an important agricultural
      area in Turkey. RESULTS: Pesticides were detected in milk samples of 11 mothers
      (34.3%) and 21 (32.8%) of milk samples. In five mothers, fungicides (in 5/10
      samples propicanozole-PP, in 4/10 samples bromucanozole-BM), in five mothers,
      organophosphates (in 10/10 samples primyphosphomethyl-PPM), in one mother, both
      organophosphates and fungicide (in 1/2 samples PPM and in 1/2 samples buprimate)
      were detected. However, the estimated daily intakes (EDI) were less than
      acceptable daily intakes (ADI) for PPM, PP and BM, respectively. CONCLUSIONS:
      Although pesticides levels in human milk did not exceed the ADIs, we suggest
      monitoring pesticides in human breast milk especially for newborn health.

PMID- 29463140
TI  - Premature ventricular beats in the athlete: management considerations.
AB  - INTRODUCTION: Premature ventricular beats (PVBs) in competitive athletes are
      incidentally found during pre-participation ECG screening. Their clinical
      significance remains debatable with several studies suggesting they are a benign
      reflection of athlete's heart, and others proposing they may indicate underlying
      structural heart disease and heightened risk for sudden cardiac death (SCD).
      Areas covered: Effective management of athletes with PVBs may best be
      accomplished using an algorithmic approach for risk stratification with a goal of
      differentiating benign PVBs from those reflective of underlying cardiomyopathies.
      Current AHA/ACC consensus recommendations provide a platform for determining
      optimal medical and invasive therapeutic strategies for symptom control and
      management of long-term complications without erroneously restricting an
      athlete's ability to play. Utilizing a shared decision-making model is an optimal
      method for managing expectations and guiding exercise recommendations. Expert
      commentary: Though pre-participation ECG screening as the standard of care for
      competitive athletes remains controversial in the United States, a 12-lead ECG is
      often the first indication of underlying structural heart disease in athletes
      with PVBs and can therefore identify athletes at greater risk of SCD.
      Advancements in non-invasive imaging continue to improve in diagnostic potential
      and prognostication. Invasive therapies provide a curative strategy for
      refractory PVBs and PVB-induced cardiomyopathy.

PMID- 29463141
TI  - The Normative Nature of Aggressive Intrusive Thinking Among an Underserved
      Incarcerated Population Compared With a Student Sample.
AB  - Aggressive intrusive thoughts (AITs) are unwanted and repetitive thoughts,
      impulses, or desires that enter into consciousness involuntarily. The current
      study compared the frequency of and distress from AITs in a sample of inmates
      jailed for violent crimes ( n = 78) versus college students ( n = 103; that is,
      participant status). The relationship between psychopathic traits and AITs was
      also explored. Results indicated that, although there were no differences between
      students and inmates, AIT frequency was positively associated with Primary
      Psychopathy. However, there was no significant interaction between participant
      status (i.e., inmate vs. student) and psychopathy. Finally, there were no
      significant main or interactions effects in the model predicting AIT distress.
      These findings demonstrate that AIT frequency is a normative cognitive experience
      that occurs in both nonviolent and violent individuals, and provides further
      evidence for an association between psychopathic traits and unwanted aggressive
      cognition.

PMID- 29463142
TI  - Levonorgestrel emergency contraceptive pills use during breastfeeding; effect on
      infants' health and development.
AB  - OBJECTIVE: The current study aims to evaluate the effect of the use of single
      packet of levonorgestrel emergency contraceptive pills (LNG-ECPs) during
      breastfeeding on the health and development of the nursing infant. MATERIALS AND
      METHODS: The current study was an ancillary observational cohort study carried
      out in a university hospital. We counseled all women delivered and planning birth
      space and breastfeed for at least 1 year for participation during postpartum
      hospital stay. Eligible participants for inclusion in the randomized controlled
      trial (NCT 01111929) were allocated to receive adequate Lactational Amenorrhea
      Method (LAM) counseling (LAM-only group) or the LAM counseling in addition to
      counseling about LNG-ECPs use (LAM + emergency contraception (EC) group). These
      pills were to be used once if unprotected intercourse did occur after expiry of
      any of the LAM prerequisites and before the couples started to use a reliable
      method of contraception. We included the first 100 women in the LAM + EC who did
      use the pills and the first 100 women in the control group who completed the
      follow-up visits for 6 months to draw the infants' outcome. The primary outcome
      was the difference of anthropometric measurements of the infants at 3 and 6
      months postpartum. Secondary outcome was the difference in the Psycho-social,
      fine and gross motor, and language development using Denver development screening
      test. RESULTS: There were no statistical significant differences between both the
      groups regarding the infants' weight, length, head circumference, chest
      circumference, and mid-arm circumference at each visit (p > .05). Additionally,
      there were no statistically significant differences regarding all items (psycho
      social, fine and gross motor, and language) of Denver development screening test
      between the infants in LAM-only and LAM + EC groups (p = .081). CONCLUSIONS: The
      use of single packet of LNG-ECPs during breastfeeding not objectively affects
      health and development of nursing infants or subjectively affects the quantity of
      breast milk.

PMID- 29463143
TI  - Estimated impact of rotavirus vaccine on hospitalizations and deaths from
      rotavirus diarrhea among children <5 in Asia.
AB  - BACKGROUND: Of the 215,000 global deaths from rotavirus estimated in 2013, 41%
      occur in Asian countries. However, despite a recommendation for global rotavirus
      vaccination since 2009, only eight countries in Asia have introduced the
      rotavirus vaccine into their national immunization program as of September 2017.
      To help policy makers assess the potential value of vaccination, we projected the
      reduction in rotavirus hospitalizations and deaths following a hypothetical
      national introduction of rotavirus vaccines in all countries in Asia using data
      on national-level rotavirus mortality, <5 population, rotavirus hospitalizations
      rates, routine vaccination coverage, and vaccine effectiveness. METHODS: To
      quantify uncertainty, we generated 1,000 simulations of these inputs. RESULTS:
      Our model predicted 710,000 fewer rotavirus hospitalizations, a 49% decrease from
      the 1,452,000 baseline hospitalizations and 35,000 fewer rotavirus deaths, a 40%
      decrease from the 88,000 baseline deaths if all 43 Asian countries had introduced
      rotavirus vaccine. Similar reductions were projected in subanalyses by vaccine
      introduction status, subregion, and birth cohort size. CONCLUSION: Rotavirus
      vaccines will substantially reduce morbidity and mortality due to rotavirus
      infections in Asia.

PMID- 29463144
TI  - Hypothermia detection in low birth weight neonates using a novel bracelet device.
AB  - OBJECTIVE: The objective of this study is to assess the diagnostic accuracy of a
      novel hypothermia monitoring and alert bracelet device (BEMPU Bracelet) in low
      birth weight (LBW) neonates weighing less than 2000 g. DESIGN: This was a
      controlled prospective study. SETTING: This study was done in the step-down
      nursery of a tertiary level newborn unit of a major teaching hospital in India.
      METHODS: Eligible cases fulfilling inclusion criteria were given BEMPU Bracelets
      for a period of 24 h. A comparison was made between skin temperatures taken at
      the axilla by a mercury thermometer and skin temperatures taken at the wrist by
      the BEMPU Bracelet. Temperatures were taken every 6 h and every time the BEMPU
      Bracelet alarmed. Trained nurses obtained temperature measurements on newborns
      during their 24-h stay in the hospital step-down nursery. RESULTS: A total of 461
      neonates were screened for hypothermia, giving 2428 temperature readings. Three
      hundred and eleven of 461 babies experienced hypothermia at some point. The 461
      babies studied experienced 495 episodes of hypothermia in total. The sensitivity
      and the specificity of the bracelet in diagnosing hypothermia were 98.6% and 95%
      respectively. The positive and negative predictive values of the bracelet were
      83.6% and 99.6%, respectively. The accuracy of the bracelet in diagnosing
      hypothermia was 95.8%. CONCLUSION: The BEMPU Bracelet is an accurate screening
      tool to detect and alert for neonatal hypothermia, thereby facilitating prompt
      management, which could prevent complications.

PMID- 29463145
TI  - LVIS Jr. stent for treatment of intracranial aneurysms with parent vessel
      diameter of 2.5 mm or less.
AB  - Background and purpose This retrospective study evaluates the safety,
      effectiveness, and long-term clinical and angiographic follow-up of intracranial
      aneurysms treated with the Low-Profile Visualized Intraluminal Support Junior
      (LVIS Jr.) stent and parent vessels of diameter equal to or less than 2.5 mm.
      Materials and methods We included all patients treated with the LVIS Jr. stent in
      aneurysms with small parent vessel diameter between March 2015 and July 2017.
      Periprocedural adverse events, immediate aneurysm occlusion rates, and clinical
      and angiographic follow-up are reported. Results A total of 35 patients with 35
      aneurysms were included. Ten aneurysms were ruptured (28.6%) and 25 were
      unruptured (71.4%). The parent arteries measured 0.9 mm to 2.5 mm in diameter
      (mean, 2.2 mm). Intra-procedural thromboembolic complications occurred in four
      patients (11.4%) and there was an intraoperative aneurysm rupture in one patient
      (2.8%). Immediate complete aneurysm occlusion was noted in 21 out of 35 patients
      (60%). Clinical follow-up ranged between one and 25 months (mean, 10.5 months)
      and magnetic resonance angiography follow-up ranged between four and 24 months
      (mean, 10.4 months). Complete aneurysm occlusion was achieved in 21 out of 29
      patients (72.4%) at last angiographic follow-up (mean, 9.4 months; range four to
      23 months). In-stent stenosis occurred in one out of 29 patients (3.4%), who was
      asymptomatic. Of the four patients with in-stent thrombosis, three patients were
      treated with "Y configuration" (two patients with middle cerebral artery
      aneurysms and one patient with an anterior communicating artery aneurysm).
      Mortality rate was 0%. Neurological morbidity was 2.9%. Conclusions Stenting with
      the LVIS Jr. stent allowed us to treat complex intracranial aneurysms with parent
      vessel diameter of 2.5 mm or less with an acceptable safety profile.

PMID- 29463146
TI  - Optimizing the first-line fertility treatment.
AB  - The objective of this study was to identify sperm score thresholds to achieve
      satisfactory intrauterine insemination (IUI) success rates according to the
      response to stimulation with clomiphene citrate (CC). To minimize the confounding
      effect of female age, we included only CC/IUI cycles of women <=35 years old. A
      total of 1,194 CC/IUI cycles were included. Semen volume, concentration, and
      motility influenced the clinical pregnancy rate (CPR). Normal morphology (>=4%)
      was associated with a comparable CPR with 3%, 2%, and 1% normal forms (15.6%,
      16.1%, 18.1%, and 13.1%, respectively). A combination of the total number of
      motile spermatozoa in the ejaculate before semen preparation (TM) at a threshold
      >=20 * 106 was associated with a CPR of 17.8% compared to 4.6% for a threshold
      <20 * 106 (p < .001). Interestingly, the TM threshold to achieve satisfactory
      outcomes was lower (10 * 106) in patients who had an optimal response to CC (>=2
      dominant follicles with an endometrial thickness >=7 mm) compared to 40 * 106 for
      those who had a suboptimal response (one dominant follicle with an endometrial
      thickness <7 mm). In conclusion, the response to superovulation with CC
      determines each patient's TM threshold required for satisfactory outcomes.
      Couples whose TM is below the threshold may benefit from a superovulation with
      gonadotropins or in vitro fertilization.

PMID- 29463147
TI  - Comparison of hepatitis B virus core-related antigen and hepatitis B surface
      antigen for predicting HBeAg seroconversion in chronic hepatitis B patients with
      pegylated interferon therapy.
AB  - AIM: Recent studies revealed that both quantitative hepatitis B surface antigen
      (qHBsAg) and hepatitis B core-related antigen (qHBcrAg) could serve as a good
      marker for predicting treatment response and indirectly reflecting intrahepatic
      cccDNA levels. This study aimed to compare the value of qHBsAg and qHBcrAg in
      predicting HBeAg seroconversion among patients undergoing PEG-IFN therapy.
      METHODS: A total of 31 HBeAg-positive patients, who underwent PEG-IFN therapy for
      12 months and follow-up for six months were retrospectively included in this
      study. The serum qHBsAg level was measured using Elecsys(r) HBsAg II Quant Assay
      and serum qHBcrAg level was measured using chemiluminescence enzyme immunoassay.
      RESULTS: During the 12-month treatment, the absolute levels of serum qHBsAg and
      qHBcrAg were both lower in patients with HBeAg seroconversion as compared to
      patients without HBeAg seroconversion, but only the difference in qHBcrAg was
      significant. During the 6-month follow-up period, both qHBsAg and qHBcrAg levels
      were rebounded significantly among patients without HBeAg seroconversion. Among
      patients with HBeAg seroconversion, no sustained significant decline of qHBsAg
      was observed, but serum qHBcrAg levels continued to decline significantly. The
      ROC curves analysis showed that both absolute qHBcrAg level and the extent of
      qHBcrAg decline at month 1 had better performance for the prediction of HBeAg
      seroconversion at month 6 after treatment, as compared to that of qHBsAg.
      CONCLUSION: Early on-treatment qHBcrAg may be a good biomarker for predicting off
      treatment HBeAg seroconversion in patients receiving PEG-IFN therapy.

PMID- 29463148
TI  - Overactive bladder syndrome treatment with ospemifene in menopausal patients with
      vulvovaginal atrophy: improvement of sexuality?
AB  - The aim of this study was to assess the effectiveness of ospemifene in the
      improvement of sexual function in postmenopausal women with vulvovaginal atrophy
      (VVA) affected by overactive bladder syndrome (OAB) or urge urinary incontinence
      (UUI). One hundred five postmenopausal patients with VVA affected by OAB and/or
      UUI were enrolled for the study. All patients received ospemifene 60 mg for 12
      weeks. Clinical examination, 3-d voiding diary and the vaginal health index (VHI)
      were performed at baseline and at 12 weeks. Patients completed the OAB-Q SF,
      FSFI, FSDS, and SF-36 questionnaires. The patient's satisfaction was also
      calculated. After 12 weeks, the reduction of urinary symptoms was observed. The
      OAB-Q symptoms, OAB-Q (HRQL) score were (55.34 +/- 13.54 vs. 23.22 +/- 9.76; p <
      .0001) and (22.45 +/- 9.78 vs. 70.56 +/- 15.49; p < .0001), before and after
      treatment. SF-36 questionnaire showed a significant improvement (p < .0001). VHI
      score increased and the women who regularly practice sexual activity increased
      after treatment. The total FSFI score increased significantly and the FSDS score
      changed after 12 weeks (p < .0001). The PGI-I after 12 weeks showed a total
      success rate of 90.5%. Ospemifene is an effective potential therapy for
      postmenopausal women with VVA affected by OAB or UUI improving sexual function
      and quality of life.

PMID- 29463149
TI  - Transition from Hybrid Capture 2 to Cobas 4800 in Hpv detection: sensitivity and
      specificity for Cin2+ in two time periods.
AB  - BACKGROUND: High-risk (HR) Human Papilloma Virus (HPV) Tests for HPV detection
      differ in sensitivity and specificity. In this study, we evaluated the
      sensitivity and specificity of the HC2 HR HPV Test and the Cobas 4800 HPV Test in
      consecutive cervical samples collected from a referral population with a high
      prevalence of disease, using CIN2+ histology as clinical outcome. METHODS: Ten
      thousand two-hundred and thirteen consecutive cervical samples were assayed for
      HR-HPV in the Laboratory Medicine Division of IEO: 5140 from January 2012 to June
      2013 with HC2 and 5073 from July 2013 to December 2014 with the Cobas HPV Test.
      These two assays differ in terms of target genes and testing methods. RESULTS:
      The test positivity rates for HC2 and Cobas 4800 were 29.5% (1515/5135, 95% CI
      28.3-30.8%) and 23.9% (1212/5069, 95% CI 22.7-25.1%), respectively. The detection
      rates of CIN2+ in the two time periods were 2.8% (145/5140, 95% CI 2.4-3.3%) and
      1.6% (79/5073, 95% CI 1.2-1.9%), respectively. The sensitivity for CIN2+ for HC2
      and Cobas 4800 was 95.2% (138/145, 95% CI 91.7-98.7%) and 93.7% (74/79, 95% CI
      88.3-99.0%), respectively. The specificity for CIN2+ for HC2 and Cobas 4800 was
      72.4% (3613/4990, 95% CI 71.2-73.6%) and 77.2% (3852/4990, 95% CI 76.0-78.4%),
      respectively. There were 23 cases of cancer in each of the two time periods. HC2
      detected 100% (23/23). Cobas 4800 detected 82.6% (19/23). CONCLUSIONS: The
      detection rate of CIN2+ was higher in the first period than in the second period.
      There was no significant difference in sensitivity of HC2 and Cobas 4800 in women
      with CIN2+. The specificity of CIN2+ using Cobas 4800 in the second period was
      higher than HC2 in the first period, probably due to the lower prevalence of
      CIN2+ in the second period.

PMID- 29463150
TI  - A noninferiority confirmatory trial of prasugrel versus clopidogrel in Japanese
      patients with non-cardioembolic stroke: rationale and study design for a
      randomized controlled trial - PRASTRO-I trial.
AB  - BACKGROUND: This comparison of PRAsugrel and clopidogrel in Japanese patients
      with ischemic STROke (PRASTRO)-I trial investigates the noninferiority of
      prasugrel to clopidogrel sulfate in the prevention of recurrence of primary
      events (ischemic stroke, myocardial infarction, and death from other vascular
      causes), and the long-term safety of prasugrel in Japanese patients with non
      cardioembolic stroke. RESEARCH DESIGN AND METHODS: This was an active-controlled,
      randomized, double-blind, double-dummy, parallel-group study conducted between
      July 2011 and March 2016 at multiple centers around Japan. Patients had to meet
      eligibility criteria before receiving 3.75 mg prasugrel or 75 mg clopidogrel
      orally once daily for a period of 96-104 weeks. RESULTS: A total of 3747 patients
      were included in this trial; 1598 in the 3.75 mg prasugrel group and 1551 in the
      75 mg clopidogrel group completed the study. During the study period, 287 (15.2%)
      patients in the prasugrel group and 311 (16.7%) in the clopidogrel group
      discontinued treatment. Baseline characteristics, safety, and efficacy results
      are forthcoming and will be published separately. CONCLUSIONS: This article
      presents the study design and rationale for a trial investigating the
      noninferiority of prasugrel to clopidogrel sulfate with regards to the inhibitory
      effect on primary events in patients with non-cardioembolic stroke.

PMID- 29463151
TI  - The role of FTO variants in the susceptibility of polycystic ovary syndrome and
      in vitro fertilization outcomes in Chinese women.
AB  - We investigated the association between single nucleotide polymorphisms (SNPs) in
      the fat mass and obesity associated (FTO) gene (rs9926289 A/G, rs79206939 A/G,
      rs9930506 A/G, rs8050136 A/C, and rs1588413 C/T) and polycystic ovary syndrome
      (PCOS), as well as outcomes of in vitro fertilization (IVF). A case-control study
      consisting of 147 PCOS patients and 120 healthy controls was conducted. FTO SNPs
      were genotyped by PCR to determine allelic frequencies, and IVF outcomes were
      analyzed. The results showed that FTO rs8050136 (p = .025) and rs1588413 (p =
      .042) were significantly associated with PCOS susceptibility, and women with risk
      alleles were often found to be obese (p < .05). For SNP rs8050136, women with AA
      + AC genotypes had higher body mass indexes (BMIs), oral glucose tolerance test/2
      h (OGTT) levels and implantation rates but lower follicle-stimulating hormone
      (FSH) and human chorionic gonadotropin (hCG) day progesterone levels and
      ovulation numbers (all p < .05) than those with the CC genotype. For SNP
      rs1588413, women carrying risk alleles exhibited higher BMIs, implantation rate,
      and levels of luteinizing hormone (LH), estradiol, and OGTT/2 h (all p < .05)
      compared with those with non-risk genotypes. Therefore, these findings suggest
      that rs8050136 and rs1588413 are associated with PCOS susceptibility, and that
      women with risk alleles have less ovulation numbers but higher implantation rates
      than those with other genotypes.

PMID- 29463152
TI  - The influence of thyroid autoimmunity on embryo quality in women undergoing
      assisted reproductive technology.
AB  - The influence of thyroid autoimmunity in assisted reproductive technology (ART)
      outcome in euthyroid women is still controversial. In this study, we
      retrospectively evaluated embryo quality in 123 euthyroid women undergoing ART
      with or without thyroid autoantibodies (TAA). Embryo quality was assessed in 119
      embryos of 29 infertile patients with TAA and in 394 embryos of 94 infertile
      patients without TAA. Our results showed not statistically significant
      differences in age, body mass index, anti-Mullerian hormone, follicle stimulating
      hormone, free triiodothyronine, and free thyroxine levels between cases and
      controls. Thyroid stimulating hormone was within the normal range, but
      significantly higher in TAA patients compared with the controls (2.4 +/- 0.8 vs.
      2 +/- 0.9 mIU/L, respectively, p < .01). The number of oocytes picked up and
      fertilized was comparable between the two groups. Embryo quality was
      significantly impaired in women with at least one autoantibody (p < .001).
      Implantation rate, pregnancy rate, and ongoing pregnancy rate were comparable in
      the two groups. These results suggest a negative impact of thyroid autoimmunity
      in embryo quality in women undergoing ART even when thyroid function is normal.

PMID- 29463153
TI  - Suspected adverse drug reaction reports with oral anticoagulants in Portugal: a
      pharmacovigilance study.
AB  - OBJECTIVE: In this pharmacovigilance study, we aimed to determine the incidence
      of spontaneously reported suspected adverse drug reactions (ADRs) related to oral
      anticoagulants: non-vitamin K antagonist oral anticoagulants (NOACs; apixaban,
      dabigatran, edoxaban, rivaroxaban) and vitamin K antagonists (VKA) Research
      design and methods: In this retrospective observational study, we extracted all
      the individual case safety reports related to oral anticoagulants recorded in the
      Portuguese Pharmacovigilance Database (January 2010 to April 2015). The annual
      incidence of suspected ADRs was estimated using drug exposure data.
      Disproportionality of reporting ADR was addressed through reporting odds ratio
      (ROR) and 99% confidence intervals. RESULTS: We appraised 794 suspected ADR (78%
      related to NOACs). The annual number of ADRs increased overtime with 9
      ADRs/million Defined Daily Dose (DDD) at the end of 2014. The incidence of NOACs
      ADRs decreased from 2012 onwards. VKA showed a disproportion in 'Investigation'
      (ROR 0.10, 99%CI 0.05-0.22) and 'Injury, poisoning and procedural complications'
      (ROR 0.36, 99%CI 0.19-0.69) ADRs compared with NOACs. NOACs had a higher
      significant disproportion of 'Nervous system disorders' related ADRs (ROR 3.98,
      99%CI 1.50-10.53). CONCLUSIONS: Reporting of ADRs associated with oral
      anticoagulants (mainly NOACs), is increasing. Exploratory disproportion analyses
      showed an increase of reports of nervous system ADRs with NOACs, and INR-related
      ADRs with VKA.

PMID- 29463154
TI  - Evaluation of changes in biochemical composition of fetal brain between 18th and
      40th gestational week in proton magnetic resonance spectroscopy.
AB  - INTRODUCTION: The aim of this study is to determine the right 1H MRS spectra of
      the brain in fetuses of different age, and then to define what metabolic changes
      occur between 18th and 40th weeks of pregnancy. METHODS: 1H MRS studies of 32
      fetuses aged 18-40 gestational weeks were performed, in which the MRI excluded
      central nervous system malformations. The studied group included 11 fetuses aged
      18-25 weeks (the second half of the second trimester), 14 fetuses aged 26-33
      weeks (the first half of the third trimester), and seven fetuses aged 34-40 weeks
      (the second half of the third trimester). The relative ratios of metabolites
      concentrations to the sum of all metabolites were calculated. RESULTS: Increase
      in the concentrations of N-acetylaspartate (NAA), Cr, Cho, and myo-inositol (mI)
      with gestational age is statistically significant. Only increase in Glx is
      statistically insignificant. In the analyzed period of pregnancy also, an
      insignificant increase of NAA/Sigma and Cr/Sigma ratios and a decrease of
      mI/Sigma, Cho/Sigma and Glx/Sigma ratios were noticed. CONCLUSIONS: Changes in
      the 1H MRS spectrum are visible with increasing age of the fetus. All studied
      substances in fetal brain change their concentrations during pregnancy, which may
      be associated with the synaptic and dendritic development as well as myelination.
      Knowledge about the chemical changes in the fetal brain can provide valuable
      information in studies of the mechanisms of pregnancy and fetal development,
      define steps of brain metabolic development and explain reasons of pathologies.

PMID- 29463155
TI  - Circulating cell-free DNA of methylated insulin-like growth factor-binding
      protein 7 predicts a poor prognosis in hepatitis B virus-associated
      hepatocellular carcinoma after hepatectomy.
AB  - The initiation and progression of hepatocellular carcinoma (HCC) is a multistage
      process involving a variety of changes at the gene level. Methylation of insulin
      like growth factor-binding protein 7 (IGFBP7) plays a crucial role in HCC
      development. The main purpose of this study was to investigate the relationship
      between oxidative stress, DNA methyltransferases (DNMTs) expression, and IGFBP7
      methylation, and to evaluate the prognostic value of serum IGFBP7 methylation
      status in patients with HCC after hepatectomy. We enrolled 155 patients with HCC
      undergoing surgical resection. The IGFBP7 methylation status, DNMTs mRNA levels
      and malondialdehyde (MDA), xanthine oxidase (XOD), reduced glutathione hormone
      (GSH), and glutathione-S-transferases (GST) levels were detected. MDA and XOD
      levels were significantly higher in IGFBP7 methylated group than unmethylated
      group, while GSH level was lower in methylated group than unmethylated group. The
      DNMT1 and DNMT3a mRNA levels were higher in IGFBP7 methylated group than
      unmethylated group. Kaplan-Meier curve analysis revealed that IGFBP7 promoter
      methylation was significantly correlated with overall survival (OS) (p < .001).
      Moreover, IGFBP7 methylation was an independent prognostic predictor for OS (p =
      .000) and early tumour recurrence (ETR) (p = .008) in HCC after hepatectomy. Our
      results indicated that IGFBP7 promoter methylation was associated with oxidative
      stress and DNMTs expression. Meanwhile, IGFBP7 promoter methylation was
      associated with OS and ETR, indicating that it might serve as a potentially
      independent prognostic factor in patients with HCC after hepatectomy.

PMID- 29463156
TI  - Vitamin D receptor gene TaqI single nucleotide polymorphism is not associated
      with lead levels in maternal and umbilical cord blood.
AB  - PURPOSE: We aimed to investigate the association of vitamin D receptor (VDR) gene
      TaqI single nucleotide polymorphism (SNPs) with serum lead (Pb) levels in
      maternal and umbilical cord blood. MATERIALS AND METHODS: Eighty-one patients who
      lived in Konya, Turkey for the last 3 years and had delivery at Baskent
      University Konya Hospital in 2016 were included in this study. Venous blood
      samples were drawn from each volunteer immediately before giving birth to
      determine the maternal Pb levels and VDR SNPs. Additionally, umbilical cord blood
      samples were collected from the umbilical vein into tube with EDTA as an
      anticoagulant immediately after birth to determine Pb levels of the fetus.
      RESULTS: The median level of Pb in the maternal blood was 29.00 (Interquartile
      Range (IQR) = 16.35) MUg/L and the median Pb level in the cord blood was 22.50
      (IQR = 9.75) MUg/L. Blood Pb level of women living in the urban area was
      significantly higher than in those living in the rural area (Z = 2.118; p =
      .034). There was a very strong positive correlation between the Pb levels in the
      maternal blood and in the umbilical cord blood (rho = 0.825, p < .001,
      respectively). Regarding VDR SNPs, "TT", "TC", and "CC" VDR TaqI genotypes were
      observed in 28 (34.6%), 45 (55.5%), and eight samples (9.9%), respectively. Pb
      levels in maternal and cord blood were higher in women with the "CC" VDR TaqI
      genotype; however, there was no statistically significant difference (p > .05).
      CONCLUSIONS: Although women with the "CC" VDR TaqI genotype had higher maternal
      and cord blood Pb levels, this was statistically insignificant and therefore, VDR
      TaqI SNPs did not significantly affect maternal and umbilical cord blood Pb
      levels.

PMID- 29463157
TI  - Comparing Recalibration Strategies for Electroencephalography-Based Decoders of
      Movement Intention in Neurological Patients with Motor Disability.
AB  - Motor rehabilitation based on the association of electroencephalographic (EEG)
      activity and proprioceptive feedback has been demonstrated as a feasible therapy
      for patients with paralysis. To promote long-lasting motor recovery, these
      interventions have to be carried out across several weeks or even months. The
      success of these therapies partly relies on the performance of the system
      decoding movement intentions, which normally has to be recalibrated to deal with
      the nonstationarities of the cortical activity. Minimizing the recalibration
      times is important to reduce the setup preparation and maximize the effective
      therapy time. To date, a systematic analysis of the effect of recalibration
      strategies in EEG-driven interfaces for motor rehabilitation has not yet been
      performed. Data from patients with stroke (4 patients, 8 sessions) and spinal
      cord injury (SCI) (4 patients, 5 sessions) undergoing two different paradigms
      (self-paced and cue-guided, respectively) are used to study the performance of
      the EEG-based classification of motor intentions. Four calibration schemes are
      compared, considering different combinations of training datasets from previous
      and/or the validated session. The results show significant differences in
      classifier performances in terms of the true and false positives (TPs) and (FPs).
      Combining training data from previous sessions with data from the validation
      session provides the best compromise between the amount of data needed for
      calibration and the classifier performance. With this scheme, the average true
      (false) positive rates obtained are 85.3% (17.3%) and 72.9% (30.3%) for the self
      paced and the cue-guided protocols, respectively. These results suggest that the
      use of optimal recalibration schemes for EEG-based classifiers of motor
      intentions leads to enhanced performances of these technologies, while not
      requiring long calibration phases prior to starting the intervention.

PMID- 29463158
TI  - The nature, magnitude, and reporting compliance of device-related events for
      intravenous patient-controlled analgesia in the FDA Manufacturer and User
      Facility Device Experience (MAUDE) database.
AB  - BACKGROUND: The aim of this study is to determine the characteristics, magnitude,
      and the quality of reporting of mandated events involving intravenous patient
      controlled analgesia (IV-PCA) devices in the Food and Drug Administration (FDA)
      Manufacturer and User Facility Device Experience (MAUDE) database; a postmarket
      surveillance system. METHODS: We utilized a mixed-methods approach to
      systematically characterize structured data and text narratives associated with
      IV-PCA events submitted to MAUDE between 1 January 2011 and 12 September 2016.
      RESULTS: Of 1,430 IV-PCA events reported during the study period, 6.4% were
      adverse events (AEs) as identified via structured data fields in the MEDWATCH
      forms. Upon qualitative review of the narrative texts, 11.0% of events were
      associated with an unfavorable clinical outcome, which was 71% higher than the
      incidence of the adverse outcomes reported using the structured data fields.
      Device-related issues, which were mostly preventable, accounted for 86.9% of
      events. Of 65 reportable events submitted by manufacturers, 18.5% did not comply
      with reporting requirements as mandated by law. CONCLUSION: Patients on IV-PCA
      continue to experience serious complications as a result of preventable errors.
      Multi-modal interventions including educational training and the development and
      adoption of PCA devices with improved safety features are needed to improve
      safety.

PMID- 29463159
TI  - Prophylactically applied Hydrofilm polyurethane film dressings reduce radiation
      dermatitis in adjuvant radiation therapy of breast cancer patients.
AB  - PURPOSE: Radiation-induced skin injury represents one of the most common side
      effects in breast cancer patients receiving adjuvant whole-breast radiotherapy.
      Numerous systemic and topical treatments have been studied in the prevention and
      management of radiation-induced skin injury without providing sustainable
      treatment strategies. While superficial barrier-forming skin products such as
      dressings are the standard of care in wound care management, their utilization as
      preventive treatment approach in radiotherapy has barely attracted attention.
      METHODS: In this prospective, intra-patient randomized study, Hydrofilm
      polyurethane film dressings were applied prophylactically to either the medial or
      lateral breast half of 62 patients with breast cancer undergoing adjuvant
      radiation therapy following breast conserving surgery. The breast half
      contralateral to the film dressing was concurrently treated with 5% urea lotion
      as control skin care. Maximum severity of radiation dermatitis was assessed using
      RTOG/EORTC toxicity scores, photospectrometric erythema measurements and patient
      assessed modified RISRAS scale. RESULTS: In the Hydrofilm compartments, mean
      maximum RTOG/EORTC radiation dermatitis severity grades were significantly
      reduced from 1.33 to 0.35 and photospectrometric measurements showed
      significantly reduced erythema severity, as compared to the control compartments,
      with an overall response rate of 89.3%. Hydrofilm completely prevented moist
      desquamation and significantly reduced patients' subjective experience of itching
      and pain. CONCLUSION: The obtained results along with a favorable cost-benefit
      ratio and an easy and quick application suggest a prophylactic application of
      Hydrofilm in adjuvant radiotherapy of breast cancer patients to reduce or even
      prevent radiation dermatitis.

PMID- 29463160
TI  - Candidate SNP of CACNA2D1 Gene Associated with Clinical Mastitis and Production
      Traits in Sahiwal (Bos taurus indicus) and Karan Fries (Bos taurus taurus * Bos
      taurus indicus).
AB  - The present study was conducted to identify polymorphisms in CACNA2D1 gene and
      their association with clinical mastitis and production traits. Exon 18 and its
      flanking regions were screened for the presence of SNPs. Statistical analysis was
      performed to identify association of period of birth, breed, and genotype with
      mastitis incidence on randomly selected 103 Sahiwal and 102 Karan Fries cattle.
      PCR-RFLP analysis revealed that g.38819398G > A mutation in exon 18 (269 bp
      amplicon) of CACNA2D1 gene resolved into AA, AG, and GG genotypes in Sahiwal and
      Karan Fries cattle. Wald chi-square analysis revealed that the period of birth,
      breed, and genotype were significantly associated with mastitis incidence. GG
      genotyped cattle were found to be less susceptible to mastitis. Least square
      analysis revealed that GG and AG genotype animals of G38819398A SNP of CACNA2D1
      gene in Sahiwal as well as in Karan Fries cattle were associated with higher
      average milk yields during 1st, 2nd, and 3rd lactations (P < 0.01). These
      observations and their differential association with the incidence of mastitis
      and production traits can be utilized as an aid to selection for simultaneous
      improvement of both antagonistic traits; however, validation of results on large
      number of animals is warranted.

PMID- 29463161
TI  - Should information about sexual health be included in education directed toward
      men with cardiovascular diseases?
AB  - BACKGROUND: Modifiable risk factors contribute to the pathogenesis of
      cardiovascular disease (CVD) and erectile dysfunction (ED). We aimed to compare
      the knowledge about the contribution of modifiable risk factors to the
      pathogenesis of CVD and ED. The impact of patients' having modifiable risk
      factors on the awareness of their negative influence on the development of CVD
      and ED was examined. METHODS: To this multicenter cohort study, we included 417
      patients with CHD who had been hospitalized in the cardiology or cardiac surgery
      department during the previous six weeks and underwent cardiac rehabilitation in
      one of the five centers. Knowledge about modifiable risk factors was collected.
      ED was assessed by an abridged IIEF-5 questionnaire. Comparisons between groups
      were conducted using the Student's t-test, Mann-Whitney U test, and Kruskal
      Wallis test. Relationships were analyzed with Spearman's rank correlation
      coefficient. RESULTS: The mean number of correctly identified risk factors for
      CVD was significantly higher than those for ED (3.71 +/- 1.87 vs. 2.00 +/- 1.94;
      p < .0001). Smoking was the most recognized risk factor both for CVD and ED.
      Dyslipidemia was least frequently identified as a risk factor for CVD. Sedentary
      lifestyle was the only risk factor whose incidence did not affect the level of
      patient knowledge. CONCLUSIONS: Cardiac patients with ED know more about risk
      factors for CVD than ED. It is necessary to include information about the
      negative impact of modifiable risk factors on sexual health into education
      programs promoting healthy lifestyles in men with cardiovascular diseases.

PMID- 29463162
TI  - Comparative in vivo evaluation of novel formulations based on alginate and silver
      nanoparticles for wound treatments.
AB  - In the present study, possibilities for using novel nanocomposites based on
      alginate and silver nanoparticles for wound treatment were investigated in a
      second-degree thermal burn model in Wistar rats. Silver nanoparticles (AgNPs)
      were electrochemically synthesized in alginate solutions that were further
      utilized to obtain the Ag/alginate solution and microfibers for subsequent in
      vivo studies. Daily applications of the Ag/alginate colloid solution, containing
      AgNPs, alginate and ascorbic acid (G3), wet Ag/alginate microfibers containing
      AgNPs (G5) and dry Ag/alginate microfibers containing AgNPs (G6) were compared to
      treatments with a commercial cream containing silver sulfadiazine (G2) and a
      commercial Ca-alginate wound dressing containing silver ions (G4), as well as to
      the untreated controls (G1). Results of the in vivo study have shown faster
      healing in treated wounds, which completely healed on day 19 (G4, G5 and G6) and
      21 (G2 and G3) after the thermal injury, while the period for complete
      reepitelization of untreated wounds (G1) was 25 days. The macroscopic analysis
      has shown that scabs fell off between day 10 and 12 after the thermal injury
      induction in treated groups, whereas between day 15 and 16 in the control group.
      These macroscopic findings were supported by the results of histopathological
      analyses, which have shown enhanced granulation and reepithelization, reduced
      inflammation and improved organization of the extracellular matrix in treated
      groups without adverse effects. Among the treated groups, dressings based on Ca
      alginate (G4-G6) induced enhanced healing as compared to the other two groups
      (G2, G3), which could be attributed to additional stimuli of released Ca2+. The
      obtained results indicated potentials of novel nanocomposites based on alginate
      and AgNPs for therapeutic applications in wound treatments.

PMID- 29463163
TI  - Staff Perceptions of Adult Day Centers Providing Post-Acute Care for Persons With
      Dementia.
AB  - The purpose of this study was to examine the perception of adult day services
      (ADS) staff and hospital discharge planners regarding the feasibility of ADS to
      provide post-acute care (PAC) for persons with dementia. We conducted key
      informant interviews with emergency department (ED) and inpatient hospital
      discharge planners ( n = 9), and two focus groups with ADS staff ( n = 15)
      representing five ADS programs. Four thematic categories were identified from the
      discharge planners, including concerns for patients, factors influencing
      discharge, experience with ADS, and conditions for ADS referrals. Four categories
      identified from ADS staff interviews include public lack of knowledge of ADS,
      communication challenges, ADS to prevent hospitalization and ED visits, and
      barriers to providing PAC. Lack of knowledge about ADS, the role of family in PAC
      decisions, and the lack of reimbursement for PAC in ADS were identified as the
      most significant drivers in the ability of ADS to provide PAC.

PMID- 29463165
TI  - Results of 14 years of brachytherapy for localized prostate cancer in Denmark:
      the Herlev cohort.
AB  - OBJECTIVE: Brachytherapy is one of several curative treatments for localized
      prostate cancer (PCa). The objective of this study was to report biochemical
      recurrence-free survival (BRFS), metastatic-free survival (MFS) and PCa-specific
      mortality after low-dose brachytherapy, stratified according to the D'Amico risk
      classification in a large Danish cohort. MATERIALS AND METHODS: The study
      population comprised 502 men treated with brachytherapy in 1998-2012. BRFS was
      defined by the Phoenix criteria. Kaplan-Meier survival analysis was used to
      estimate BRFS and MFS. The cumulative PCa mortality was analysed using competing
      risk analyses. Multivariable Cox regression analysis was used to estimate risk of
      biochemical recurrence. RESULTS: In total, 206 men were classified with low-risk
      PCa, 265 men with intermediate-risk PCa and 33 men with high-risk PCa. Median
      follow-up was 6.6 years [95% confidence interval (CI) 6.2-7.0]. The 10 year BRFS
      was 90% (95% CI 83-97), 75% (95% CI 65-87) and 75% (95% CI 59-92) in men with low
      , intermediate- and high-risk PCa, respectively. The 10 year MFS was 95% (95% CI
      89-100), 93% (95% CI 88-98) and 78% (95% CI 57-99) in men with low-, intermediate
      and high-risk PCa, respectively. The 10 year cumulative incidence of PCa
      mortality was 1% (95% CI 0-3), 5% (95% CI 0-12) and 11% (95% CI 0-25) for men
      with low-, intermediate- and high-risk PCa, respectively. CONCLUSIONS: Low-dose
      brachytherapy offers good short- to intermediate-term cancer control in selected
      men with localized PCa. Further studies are needed for safety analyses and for
      comparison with other treatment modalities.

PMID- 29463164
TI  - Apolipoprotein E epsilon4 Genotype Is Associated with Elevated Psychiatric
      Distress in Veterans with a History of Mild to Moderate Traumatic Brain Injury.
AB  - As few studies have examined the relationship between the apolipoprotein E (APOE)
      gene and clinical outcomes after military-related traumatic brain injury (TBI),
      we aimed to determine whether the epsilon4 allele of the APOE gene influences
      neuropsychiatric symptoms in veterans with a history of mild-to-moderate TBI.
      Participants included 133 veterans (TBI = 79; military controls [MC] = 54) who
      underwent APOE genotyping and were divided into epsilon4+ (TBI = 18; MC = 15) and
      epsilon4- (TBI = 61; MC = 39) groups. All participants underwent evaluation of
      psychological distress using the Beck Depression Inventory-II, Beck Anxiety
      Inventory, and PTSD Checklist-Military Version. Two-way analyses of variance were
      conducted to examine the effect of group (TBI vs. MC) and APOE-epsilon4 status
      (epsilon4+ vs. epsilon4-) across symptom measures. There was a significant main
      effect of group across all symptom measures (TBI > MC; all p values <0.001), no
      main effect of epsilon4 genotype (p = 0.152-0.222), and a significant interaction
      of group by epsilon4 genotype across all measures (p = 0.027-0.047).
      Specifically, for TBI participants, epsilon4+ veterans demonstrated significantly
      higher symptom scores across all measures when compared to epsilon4- veterans (p
      = 0.007-0.015). For MC participants, epsilon4 status had no effect on the
      severity of psychiatric symptom scores (p = 0.585-0.708). Our results demonstrate
      that, in our well-characterized sample of veterans with history of neurotrauma,
      possession of the epsilon4 allele conveys risk for increased symptomatology
      (i.e., depression, anxiety, and post-traumatic stress disorder), even well
      outside of the acute phase of injury. Findings suggest a meaningful relationship
      between APOE genotype and psychiatric distress post-TBI, and they suggest that
      there is a brain basis for the complex neuropsychiatric presentation often
      observed in this vulnerable population. Future longitudinal studies are needed in
      order to further our understanding of how genetic factors influence response to
      TBI.

PMID- 29463166
TI  - Clinicopathological indicators of survival among patients with pulmonary
      carcinoid tumor.
AB  - BACKGROUND: Pulmonary carcinoids (PC) are rare malignant neoplasms that cover
      approximately 1% of all lung cancers. PCs are classified by histological criteria
      as either typical (TC) or atypical (AC). Histological subtype is the most studied
      prognostic factor. The aim of this study was to evaluate if other tissue or
      clinical features are associated with patient outcomes. MATERIAL AND METHODS: We
      retrospectively reviewed clinical records of 133 PC patients who underwent
      operation in the Helsinki University Hospital between 1990 and 2013. Tissue
      specimens were re-evaluated, processed into tissue microarray format and stained
      immunohistochemically with serotonin, calcitonin, adrenocorticotropic hormone
      (ACTH), thyroid transcription factor-1 (TTF-1) and Ki-67. Survival and risk
      analyses were performed. RESULTS: Based on histology, 75% (n = 100) of the tumors
      were TCs and 25% (n = 33) ACs. TCs had higher 10-year disease-specific survival
      (DSS) rate than ACs (99% (95% CI, 93-100%) for TCs vs. 82% (95% CI, 61-92%) for
      ACs). Hormonally active tumors expressing serotonin, calcitonin or ACTH were
      noted in 53% of the specimens but hormonal expression was not associated with
      DSS. TTF-1 was positive in 78% of the specimens but was not associated with DSS.
      Ki-67 index varied between <1% and 15%. Ki-67 >= 2.5% was associated with shorter
      DSS (p = .004). The presence of metastatic disease (p = .001), tumor size >=30 mm
      (p = .021) and atypical histology (p = .011) were also associated with disease
      specific mortality. CONCLUSIONS: We conclude that PCs are uncommon tumors. When
      resected, the long-term survival is in general favorable. In this consecutive,
      single-institution cohort of patients, presence of metastatic disease, tumor
      size, histological subtype and Ki-67 index were associated with shorter disease
      specific survival. As TC and AC have different clinical behaviors, the correct
      tumor classification at the time of diagnosis is a necessity.

PMID- 29463167
TI  - Conducting neuropsychological assessment with transgender individuals.
AB  - OBJECTIVE: The purpose of this paper is to provide an overview of helpful
      clinical practices when working with transgender adult individuals. METHOD: While
      the number of openly transgender individuals appears to be growing with society's
      increased acceptance and awareness, many neuropsychologists have had few
      opportunities to gain experience with this patient population. In this article,
      we review the existing literature as it relates to clinical neuropsychological
      practice. RESULTS: We describe important terminology, ideals for creating an
      environment of respect, and how existing clinical guidelines for transgender
      individuals may apply to neuropsychology. In addition, we review the primary
      steps in the assessment process and provide a set of principles and
      recommendations for conducting neuropsychological assessments with transgender
      patients. CONCLUSIONS: There is a paucity of guidance in the field for working
      with transgender individuals. This article represents a step forward in the
      dialog and we look forward to future research that develops appropriate normative
      information, increases understanding of psychosocial factors, and better
      appreciates the range of hormonal influences for transgender individuals.

PMID- 29463168
TI  - Associated Mortality of Liberal Fluid Administration in Sepsis.
AB  - Fluid resuscitation, to restore intravascular volume and improve oxygen delivery,
      is a crucial step in early resuscitation efforts of patients with sepsis or
      septic shock. The 2016 Surviving Sepsis Campaign guidelines suggest the use of
      dynamic versus static measures of fluid responsiveness and fluid resuscitation
      with at least 30 mL/kg of intravenous crystalloid within the first 3 hours
      followed by fluid administration if hemodynamic factors continue to improve.
      Despite these recommendations, risks to this practice may exist as multiple
      studies have demonstrated an association between a positive fluid balance and/or
      administration of large fluid volume and increase in mortality. These studies are
      limited by variations in their methodologic design; therefore, cause and effect
      cannot yet be determined. Future multicenter, randomized, controlled studies that
      evaluate fluid balance and fluid volume need to be conducted to clarify the role
      of fluid administration to patients with sepsis to maximize benefits and minimize
      risk.

PMID- 29463169
TI  - Clinical Outcomes of Student Pharmacist-Driven Medication Histories at an
      Academic Medical Center.
AB  - BACKGROUND: Many studies have shown the positive impact that student pharmacists
      have on patients' health; however, no studies have been published evaluating
      student pharmacists' impact on direct patient outcomes (ie, readmission,
      emergency department [ED] visits, length of stay) related to the medication
      history process. OBJECTIVE: To evaluate the impact of student pharmacist-obtained
      medication histories on identification of medication discrepancies and clinical
      outcomes. METHODS: Student pharmacists obtained medication histories and then
      compared the history to that obtained by other health-care providers. Students
      documented discrepancies and interventions were completed. Control patients were
      identified and discharge medication list and 30-day readmissions were compared.
      RESULTS: Seventeen students conducted 215 patient interviews, and 1848
      modifications were made to documented home medications in the electronic medical
      record. Compared to controls (n = 148 student pharmacist, 149 controls), a
      nonsignificant improvement was found in discharge medication list completeness
      scores in patients seen by student pharmacists (3.94 vs 3.63; P = .06); but no
      difference was found in accuracy scores (0.92 vs 0.93; P = .41). Fewer ED visits
      at 30 days were found in the student pharmacist group (8 vs 18; P = .045), with
      no difference in readmissions. CONCLUSIONS: Student pharmacist-obtained
      medication histories improved the information available for identifying drug
      related problems for inpatients, completeness of the discharge medication list,
      and ED visits within 30 days.

PMID- 29463170
TI  - Electronic Transport in Two-Dimensional Materials.
AB  - Two-dimensional (2D) materials have captured the attention of the scientific
      community due to the wide range of unique properties at nanometer-scale
      thicknesses. While significant exploratory research in 2D materials has been
      achieved, the understanding of 2D electronic transport and carrier dynamics
      remains in a nascent stage. Furthermore, because prior review articles have
      provided general overviews of 2D materials or specifically focused on charge
      transport in graphene, here we instead highlight charge transport mechanisms in
      post-graphene 2D materials, with particular emphasis on transition metal
      dichalcogenides and black phosphorus. For these systems, we delineate the
      intricacies of electronic transport, including band structure control with
      thickness and external fields, valley polarization, scattering mechanisms,
      electrical contacts, and doping. In addition, electronic interactions between 2D
      materials are considered in the form of van der Waals heterojunctions and
      composite films. This review concludes with a perspective on the most promising
      future directions in this fast-evolving field.

PMID- 29463171
TI  - Malignant hydrocele: a rare manifestation of peritoneal carcinomatosis of
      colorectal origin as a transcoelomic spread into the scrotum - case report and
      literature overview.

PMID- 29463172
TI  - Radiation-induced G2/M arrest rarely occurred in glioblastoma stem-like cells.
AB  - PURPOSE: The purpose of this study is to systematically study the cell-cycle
      alterations of glioblastoma stem-like cells (GSLCs) after irradiation, possibly
      enriching the mechanisms of radioresistance of GSLCs. MATERIALS AND METHODS:
      GSLCs were enriched and identified, and then the radioresistance of GSLCs was
      validated by analyzing cell survival, cell proliferation, and radiation-induced
      apoptosis. The discrepancy of the cell-cycle distribution and expression of cell
      cycle-related proteins between GSLCs and glioblastoma differentiated cells (GDCs)
      after irradiation was completely analyzed. RESULTS: The survival fractions and
      the cell viabilities of GSLCs were significantly higher than those of GDCs after
      irradiation. Radiation-induced apoptosis was less prominent in GSLCs than in
      GDCs. After irradiation with high-dose X-rays, the percentages of GDCs in G2/M
      phase was evidently increased. However, radiation-induced G2/M arrest occurred
      less frequently in GSLCs, but S-phase arrest occurred in GSLCs after irradiation
      with 8 Gy. Further mechanistic studies showed that the expressions levels of
      Cdc25c, Cdc2, and CyclinB1 in GSLCs were not apparently changed after
      irradiation, while those of p-ATM and p-Chk1 were sharply increased after
      irradiation in GSLCs. The basal level of Cdc25c expression in GSLCs was much
      higher than that in GDCs. CONCLUSIONS: We explored the cell-cycle alterations and
      cell-cycle-related proteins expression levels in GSLCs after irradiation,
      providing a novel mechanism of radioresistance of GSLCs.

PMID- 29463173
TI  - Dr Amos G Babcock - fact or fiction?
AB  - The War of 1812-1814 between the United States of America and Great Britain gave
      rise to several journals relating the sufferings of prisoners of war confined in
      prison ships and gaols in England. One of these is A journal of a young man of
      Massachusetts, said to have been written by Dr Amos G Babcock, an American ship's
      surgeon, and first published in 1816. This article sets out arguments for and
      against the truth of this assertion.

PMID- 29463174
TI  - Cumulative use of salivary markers with an adaptive design improves detection of
      periodontal disease over fixed biomarker thresholds.
AB  - OBJECTIVE: Aim was to analyze the diagnostic ability of cumulative risk score
      (CRS), which uses salivary levels of Porphyromonas gingivalis, interleukin (IL)
      1beta, and matrix metalloproteinase (MMP)-8 in an adaptive design, compared to
      previously reported thresholds of each marker alone. MATERIALS AND METHODS: Oral
      and general health information of 463 participants were included in the analysis.
      Having the percentage of bleeding on probing (BOP) > 25%, having at least two
      sites with probing pocket depth (PPD) of 4-5 mm or having at least one tooth with
      alveolar bone loss (ABL) of at least 1/3 of the root length were accepted as
      outcome variables. Being above the salivary threshold concentrations of P.
      gingivalis, IL-1beta, and MMP-8 and CRS values were used as explanatory
      variables. Receiver operating characteristics (ROC) producing an area under the
      curve (AUC) and multinomial regression analysis were used in statistical
      analysis. RESULTS: CRS provided AUCs larger than any other tested biomarker
      threshold. Sensitivity and specificity of CRS for detecting clinical markers of
      periodontitis were acceptable, and a strong association was observed between the
      highest CRS score and having at least two sites with PPD of 4-5 mm. CONCLUSION:
      CRS brings additional power over fixed thresholds of single biomarkers in
      detecting periodontitis.

PMID- 29463175
TI  - Developing a cultural context for conducting a neuropsychological evaluation with
      a culturally diverse client: the ECLECTIC framework.
AB  - OBJECTIVE: With the increasing diversification of the American population, the
      discipline of neuropsychology is challenged to develop appropriate tools and
      conceptual models to meet its evolving client base. Thus far, the focus has been
      on developing appropriate tests and norms to obtain accurate testing data. By
      contrast, far less attention has been paid to the contextual impact of culture on
      an evaluation. This paper attempts to address this shortcoming. METHODS: This
      manuscript introduces the ECLECTIC framework for conceptualizing different facets
      of culture pertinent for understanding a culturally diverse client when
      conducting a neuropsychological evaluation. Individual components of the
      framework (E: education and literacy; C: culture and acculturation; L: language;
      E: economics; C: communication; T: testing situation: comfort and motivation; I:
      intelligence conceptualization; and C: context of immigration) are introduced and
      potential biases to fairness in testing are described. In this manner, the
      framework specifies how individual facets of culture can impact
      neuropsychological test performance. CONCLUSIONS: Clinical implementation of the
      framework will be illustrated with a case sample. Strengths and weaknesses of the
      framework are discussed as well as recommendations for implementation.

PMID- 29463176
TI  - Neuroinflammation after Traumatic Brain Injury Is Enhanced in Activating
      Transcription Factor 3 Mutant Mice.
AB  - Traumatic brain injury (TBI) induces a neuroinflammatory response resulting in
      astrocyte and microglia activation at the lesion site. This involves upregulation
      of neuroinflammatory genes, including chemokines and interleukins. However, so
      far, there is lack of knowledge on transcription factors (TFs) modulating this
      TBI-associated gene expression response. Herein, we analyzed activating
      transcription factor 3 (ATF3), a TF encoding a regeneration-associated gene (RAG)
      predominantly studied in peripheral nervous system (PNS) injury. ATF3 contributes
      to PNS axon regeneration and was shown before to regulate inflammatory processes
      in other injury models. In contrast to PNS injury, data on ATF3 in central
      nervous system (CNS) injury are sparse. We used Atf3 mouse mutants and a closed
      head weight-drop-based TBI model in adult mice to target the rostrolateral cortex
      resulting in moderate injury severity. Post-TBI, ATF3 was upregulated already at
      early time points (i.e,. 1-4 h) post-injury in the brain. Mortality and weight
      loss upon TBI were slightly elevated in Atf3 mutants. ATF3 deficiency enhanced
      TBI-induced paresis and hematoma formation, suggesting that ATF3 limits these
      injury outcomes in wild-type mice. Next, we analyzed TBI-associated RAG and
      inflammatory gene expression in the cortical impact area. In contrast to the PNS,
      only some RAGs (Atf3, Timp1, and Sprr1a) were induced by TBI, and, surprisingly,
      some RAG encoding neuropeptides were downregulated. Notably, we identified ATF3
      as TF-regulating proneuroinflammatory gene expression, including CCL and CXCL
      chemokines (Ccl2, Ccl3, Ccl4, and Cxcl1) and lipocalin. In Atf3 mutant mice, mRNA
      abundance was further enhanced upon TBI compared to wild-type mice, suggesting
      immune gene repression by wild-type ATF3. In accord, more immune cells were
      present in the lesion area of ATF3-deficient mice. Overall, we identified ATF3 as
      a new TF-mediating TBI-associated CNS inflammatory responses.

PMID- 29463177
TI  - The combination of targeted and systematic prostate biopsies is the best protocol
      for the detection of clinically significant prostate cancer.
AB  - OBJECTIVE: Compared with standard systematic transrectal ultrasound (TRUS)-guided
      biopsies (SBx), targeted biopsies (TBx) using magnetic resonance imaging
      (MRI)/TRUS fusion could increase the detection of clinically significant prostate
      cancer (PCa-s) and reduce non-significant PCa (PCa-ns). This study aimed to
      compare the performance of the two approaches. MATERIALS AND METHODS: A
      prospective, single-center study was conducted on all consecutive patients with
      PCa suspicion who underwent prebiopsy multiparametric MRI (mpMRI) using the
      Prostate Imaging Reporting and Data System (PI-RADS). All patients underwent
      mpMRI/TRUS fusion TBx (two to four cores/target) using UroStationTM (Koelis,
      Grenoble, France) and SBx (10-12 cores) during the same session. PCa-s was
      defined as a maximal positive core length >=4 mm or Gleason score >=7. RESULTS:
      The study included 191 patients (at least one suspicious lesion: PI-RADS >=3).
      PCa was detected in 55.5% (106/191) of the cases. The overall PCa detection rate
      and the PCa-s detection rate were not significantly higher in TBx alone versus
      SBx (44.5% vs 46.1%, p = .7, and 38.2% vs 33.5%, p = .2, respectively). Combined
      TBx and SBx diagnosed significantly more PCa-s than SBx alone (45% vs 33.5%, p =
      .02). PCa-s was detected only by TBx in 12% of cases (23/191) and only by SBx in
      7.3% (14/191). Gleason score was upgraded by TBx in 16.8% (32/191) and by SBx in
      13.6% (26/191) of patients (p = .4). CONCLUSIONS: The combination of TBx and SBx
      achieved the best results for the detection and prognosis of PCa-s. The use of
      SBx alone would have missed the detection of PCa-s in 12% of patients.

PMID- 29463178
TI  - Interim FDG-PET/CT in Hodgkin lymphoma: what are we actually looking at?

PMID- 29463179
TI  - Analysis of Genetic Diversity and Structure of Guanzhong Horse Using
      Microsatellite Markers.
AB  - To determine the genetic diversity and validate the pedigree record of Chinese
      Guanzhong horse, 67 individuals were genotyped with eight microsatellite markers.
      In our study, the mean observed and expected heterozygosities were 0.51 and 0.66,
      respectively. The mean observed number of alleles for the Guanzhong horse was
      3.88. Nonetheless, the total value of FST multiloci clearly indicates that about
      0.5% of overall genetic variation is due to line founder differences, while
      differences among individuals are responsible for the remaining 99.5%. In
      addition, the polymorphic information content (PIC) result showed that five loci
      (HTG7, HMS7, HMS2, AHT4, and HMS6) were highly polymorphic (PIC > 0.5) and three
      loci (HMS3, HTG6, and COR071) were moderate polymorphic (PIC > 0.25). Genetic
      distances and cluster analysis showed that the genetic relationship among 67
      Guanzhong horse was generally consistent with pedigree recorded. Our results not
      only evaluated the genetic diversity of Chinese Guanzhong horse, but also
      suggested that the eight microsatellite markers might be used as subservient
      markers for parentage verification and individual identification in the Guanzhong
      horse.

PMID- 29463180
TI  - The association between physical activity and dietary inflammatory index on
      mortality risk in U.S. adults.
AB  - OBJECTIVE: Both diet and physical activity have been shown to be associated with
      reduced risk for mortality. The current study examined the individual and
      combined effects of the inflammatory quality of diet and physical activity levels
      on mortality risk. METHODS: Data from the 1999-2004 National Health and Nutrition
      Examination Survey were used (N = 10,610 adults 20-85 years). Participants were
      followed through 2011, entailing a median follow-up time of 9.6 yrs. Dietary
      patterns were assessed using the Dietary Inflammatory Index (DII(r)), with a
      higher score indicative of greater diet-related inflammation. Habitual physical
      activity was assessed via a 30-day recall of leisure-time physical activity as
      well as objectively via up to seven days of accelerometry assessment. Four
      lifestyle groups were created: 1) unfavorable DII and inactive (referent); 2)
      unfavorable DII and active; 3) favorable DII and inactive; and 4) favorable DII
      and active. RESULTS: Those who had a low DII score (favorable) and who self
      reported being active had a 39% reduced hazard of all-cause mortality (HR = 0.61;
      95% CI: 0.49-0.76) when compared to those with a higher DII and were inactive.
      Results based on accelerometer-assessed physical activity indicate a 65% reduced
      hazard (HR = 0.35; 95% CI: 0.17-0.74). DII and physical activity also were
      individually associated with mortality in the expected direction. Specifically,
      DII was positively associated (HR = 1.08; 95% CI: 1.04-1.13) and physical
      activity inversely associated (HR = 0.97; 95% CI: 0.94-0.99) with all-cause
      mortality risk. CONCLUSION: The combination of consuming a more anti-inflammatory
      diet and having adequate levels of physical activity is associated with a reduced
      risk of mortality. Additional replicative work is warranted.

PMID- 29463181
TI  - Spared behavioral repetition effects in Alzheimer's disease linked to an altered
      neural mechanism at posterior cortex.
AB  - OBJECTIVE: Individuals with dementia of the Alzheimer type (AD) classically show
      disproportionate impairment in measures of working memory, but repetition
      learning effects are relatively preserved. As AD affects brain regions implicated
      in both working memory and repetition effects, the neural basis of this
      discrepancy is poorly understood. We hypothesized that the posterior repetition
      effect could account for this discrepancy due to the milder effects of AD at
      visual cortex. METHOD: Participants with early AD, amnestic mild cognitive
      impairment (MCI), and healthy controls performed a working memory task with
      superimposed repetition effects while electroencephalography was collected to
      identify possible neural mechanisms of preserved repetition effects. RESULTS:
      Participants with AD showed preserved behavioral repetition effects and a change
      in the posterior repetition effect. CONCLUSION: Visual cortex may play a role in
      maintained repetition effects in persons with early AD.

PMID- 29463183
TI  - Younger and older adults' associative memory for medication interactions of
      varying severity.
AB  - While older adults face various deficits in binding items in memory, they are
      often able to remember information that is deemed important. In Experiment 1, we
      examined how younger and older adults remember medication interactions of varying
      severity. There were no age differences in overall memory accuracy, but older
      adults' performance depended on the severity of the interactions (such that the
      interactions associated with the most severe health outcomes were remembered most
      accurately) while younger adults' did not. In Experiment 2, a similar task was
      designed to create interference in memory. Even with this more difficult task
      there were no age differences in recall accuracy, and both age groups remembered
      the interactions with the severe outcomes most accurately. These findings suggest
      that, under certain circumstances, older adults do not face deficits in
      associative recognition accuracy of information that varies in importance.

PMID- 29463182
TI  - Registered Replication Report: Dijksterhuis and van Knippenberg (1998).
AB  - Dijksterhuis and van Knippenberg (1998) reported that participants primed with a
      category associated with intelligence ("professor") subsequently performed 13%
      better on a trivia test than participants primed with a category associated with
      a lack of intelligence ("soccer hooligans"). In two unpublished replications of
      this study designed to verify the appropriate testing procedures, Dijksterhuis,
      van Knippenberg, and Holland observed a smaller difference between conditions (2%
      3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but
      women did not (0.3% and -0.3%). The procedure used in those replications served
      as the basis for this multilab Registered Replication Report. A total of 40
      laboratories collected data for this project, and 23 of these laboratories met
      all inclusion criteria. Here we report the meta-analytic results for those 23
      direct replications (total N = 4,493), which tested whether performance on a 30
      item general-knowledge trivia task differed between these two priming conditions
      (results of supplementary analyses of the data from all 40 labs, N = 6,454, are
      also reported). We observed no overall difference in trivia performance between
      participants primed with the "professor" category and those primed with the
      "hooligan" category (0.14%) and no moderation by gender.

PMID- 29463184
TI  - Informal work-related injuries: a one year prospective study in a rural community
      in Serbia.
AB  - Work-related injuries occurring during informal work often go unreported, yet
      lead to significant mortality and contribute substantially to disease burden due
      to injury-related disability. In Serbia, injury is a leading cause of death, with
      work-related injuries comprising a significant proportion. This study explored
      the frequency of and risk factors for these injuries in a rural Serbian
      community. During the 12-month study period, physicians from a municipal Primary
      Care Centre reported all presenting injuries using a specific injury report form.
      One in four injuries reported occurred during informal work practices, accounting
      for 71% of all reported work-related injuries. These occurred within the
      household in 85% of cases, and were more severe in males (79%). Regarding work
      related injuries, informal workers were significantly older than formally
      employed workers, regardless of sex. Public policy should address safety
      improvements for informal workers, via provision of relevant training and
      protective equipment.

PMID- 29463185
TI  - Concomitant resolution through fecal microbiota transplantation of Clostridium
      difficile and OXA-48-producing Klebsiella pneumoniae.

PMID- 29463186
TI  - Daily Profiles of Light Exposure and Evening Use of Light-emitting Devices in
      Young Adults Complaining of a Delayed Sleep Schedule.
AB  - A number of factors can contribute to a delayed sleep schedule. An important
      factor could be a daily profile of light exposure favoring a later circadian
      phase. This study aimed to compare light exposure between 14 young adults
      complaining of a delayed sleep schedule and 14 matched controls and to identify
      possible associations between habitual light exposure and circadian phase.
      Exposure to white and blue light was recorded with ambulatory monitors for 7
      consecutive days. Participants also noted their daily use of light-emitting
      devices before bedtime. Endogenous circadian phase was estimated with the dim
      light melatonin onset (DLMO) in the laboratory. The amplitude of the light-dark
      cycle to which the subjects were exposed was smaller in delayed than in control
      subjects, and smaller amplitude was associated with a later DLMO. Smaller
      amplitude was due to both decreased exposure in the daytime and increased
      exposure at night. Total exposure to blue light, but not to white light, was
      lower in delayed subjects, possibly due to lower exposure to blue-rich outdoor
      light. Lower daily exposure to blue light was associated with a later DLMO.
      Timing of relative increases and decreases of light exposure in relation to
      endogenous circadian phase was also compared between the 2 groups. In delayed
      subjects, there was a relatively higher exposure to white and blue light 2 h
      after DLMO, a circadian time with maximal phase-delaying effect. Delayed
      participants also had higher exposure to light 8 to 10 h after DLMO, which
      occurred mostly during their sleep episode but may have some phase-advancing
      effects. Self-reported use of light-emitting devices before bedtime was higher in
      delayed than in control subjects and was associated with a later DLMO. This study
      suggests that individuals complaining of a delayed sleep schedule engage in light
      related behaviors favoring a later circadian phase and a later bedtime.

PMID- 29463187
TI  - Finding Keys: A Systematic Review of Barriers and Facilitators for Refugee
      Children's Disclosure of Their Life Stories.
AB  - The systematic review presented in this article aims to reveal what supports and
      hampers refugee children in telling their, often traumatic, life stories. This is
      important to ensure that migration decisions are based on reliable information
      about the children's needs for protection. A systematic review was conducted in
      academic journals, collecting all available scientific knowledge about the
      disclosure of life stories by refugee minors in the context of social work,
      guardianship, foster care, asylum procedures, mental health assessment, and
      therapeutic settings. The resulting 39 studies were thoroughly reviewed with
      reference to what factors aided or hampered the refugee children's disclosure of
      their life stories. The main barriers to disclosure were feelings of mistrust and
      self-protection from the side of the child and disrespect from the side of the
      host community. The facilitators for disclosing life stories were a positive and
      respectful attitude of the interviewer, taking time to build trust, using
      nonverbal methods, providing agency to the children, and involving trained
      interpreters. Social workers, mentors, and guardians should have time to build
      trust and to help a young refugee in revealing the life story before the minor is
      heard by the migration authorities. The lack of knowledge on how refugee children
      can be helped to disclose their experiences is a great concern because the
      decision in the migration procedure is based on the story the child is able to
      disclose.

PMID- 29463188
TI  - Progesterone Inhibits Apoptosis in Fetal Membranes by Altering Expression of Both
      Pro- and Antiapoptotic Proteins.
AB  - OBJECTIVE: Progesterone supplementation prevents preterm birth (PTB) in some high
      risk women, but its mechanism of action is unknown. One-third of PTB is
      associated with preterm premature rupture of membranes (PPROMs). We have
      previously shown that progesterone inhibits basal and Tumor Necrosis Factor (TNF)
      alpha-induced apoptosis in an explant model of human fetal membranes. This study
      investigates the molecular mechanisms responsible for progesterone-mediated
      inhibition of apoptosis in fetal membranes. METHODS: Human fetal membranes were
      collected at elective cesarean at term (no labor, no infection; n = 6), washed,
      and pretreated with/without progesterone (125 ng/mL) for 24 hours. Thereafter,
      membranes were treated with/without TNFalpha (50 ng/mL) and/or progesterone for
      48 hours, harvested, and homogenized. Apoptosis was determined by evaluating
      caspase-3, -8, and -9 activities. Expression of pro- BH3 interacting domain death
      against, Bc1-2 associated X protein (BID, BAX) and antiapoptotic proteins (X
      linked inhibitor of apoptosis protein [XIAP], Bcl-2, FLICE inhibitory protein
      [FLIP]) were measured by Western blot. RESULTS: TNFalpha increased apoptosis
      (measured by caspase-3, -8, and -9 activities) in fetal membranes, and this
      effect was abrogated by progesterone. Under basal conditions, progesterone
      suppressed expression of the proapoptotic protein, BID, by 0.45 (0.14)-fold, and
      increased expression of the antiapoptotic proteins, Bcl-2 and XIAP; no change was
      seen in BAX or FLIP. In contrast, TNFalpha increased BID expression by 5.15
      (2.92)-fold, which was prevented by pretreatment with progesterone. CONCLUSIONS:
      Progesterone inhibits apoptosis in fetal membranes by suppressing expression of
      the proapoptotic protein, BID (for both basal and TNFalpha-induced apoptosis),
      and upregulating expression of the antiapoptotic proteins, XIAP and Bcl-2 (under
      basal conditions only). These data provide a mechanism by which progesterone
      supplementation may prevent PPROM and PTB in some women at high risk.

PMID- 29463189
TI  - A Qualitative Investigation of the Role of Gender in Young Women's Dating
      Violence in the United States.
AB  - The relevance of gender has been a central debate in the intimate partner
      violence (IPV) literature. The current qualitative study explored the role of
      gender in shaping the social context, meaning, and reception of young women's IPV
      in the United States. A total of 36 undergraduate women were recruited from a
      larger sample for in-depth interviews. Emergent themes suggest that women's
      violence was construed as nonequivalent to men's violence, including the
      perceived triviality of women's violence, contingencies under which women's
      violence is deemed acceptable, and the status of male IPV as unacceptable. Gender
      was important for participants and bystanders in determining whether they
      interpreted behaviors as meaningful acts of violence.

PMID- 29463190
TI  - CYFRA 21-1 predicts the efficacy of nivolumab in patients with advanced lung
      adenocarcinoma.
AB  - CYFRA 21-1 is a prognostic marker for non-small cell lung cancer. The serum CYFRA
      21-1 level is also known as an adjunct for the diagnosis of lung squamous cell
      carcinoma. This study aimed to examine whether CYFRA 21-1 has predictive
      implications for nivolumab therapy in patients with advanced lung adenocarcinoma.
      Of the 79 patients who were treated with nivolumab therapy at the Shizuoka Cancer
      Center between December 2015 and September 2016, we retrospectively reviewed the
      data of 50 patients. The patient characteristics were as follows: age <70/>=70
      years: 43 (86%)/7; male/female: 31 (62.0%)/19; Eastern Cooperative Oncology Group
      performance status 0-1/2: 43 (86%)/7; smoking status: no/yes: 18 (36%)/32;
      epidermal growth factor receptor mutation status negative/positive: 36 (72%)/14;
      CYFRA 21-1 >=2.2/<2.2 ng/mL: 28 (56%)/22; carcinoembryonic antigen >=5/<5 ng/mL:
      29 (58%)/21; and number of prior regimens 2-3/>=4: 16 (32%)/34. With a median
      follow-up of 263.5 (range, 64-352) days, the median progression-free survival was
      70 days. The clinical variables investigated using univariate analysis were as
      follows: age (p = 0.423), carcinoembryonic antigen (p = 0.888), epidermal growth
      factor receptor mutation status (p = 0.105), performance status (p = 0.968), sex
      (p = 0.210), number of prior regimens (p = 0.146), CYFRA 21-1 (p = 0.026), and
      smoking status (p = 0.041). A multivariate analysis identified a serum CYFRA 21-1
      level >=2.2 ng/mL as an independent predictor of a favorable outcome (hazard
      ratio, 0.44; 95% confidence interval, 0.23-0.85; p = 0.015; median progression
      free survival, 155 vs 51.5 days). In conclusion, CYFRA 21-1 might be an
      independent predictor of outcome for patients with advanced lung adenocarcinoma
      treated with nivolumab.

PMID- 29463191
TI  - HE4 is superior to CA125 in the detection of recurrent disease in high-risk
      endometrial cancer patients.
AB  - OBJECTIVE: To date, biomarkers are not routinely used in endometrial cancer
      diagnosis, prognosis, and follow-up. The purpose of this study was to evaluate
      whether serum HE4 was related to clinicopathological risk factors and outcome.
      Second, the role of serum HE4 and CA125 was assessed as indicator for recurrent
      disease during follow-up. METHODS: A total of 174 patients with endometrial
      cancer between 1999 and 2009 were selected for this retrospective study. Serum
      HE4 and CA125 were analyzed at primary diagnosis, during follow-up, and at the
      time of recurrence. Correlations with clinicopathological factors were studied by
      univariate and multivariate survival analyses. Lead time was calculated in order
      to determine which serum marker was elevated prior to clinical detection of
      recurrent disease. RESULTS: Serum levels of HE4 and CA125 were significantly
      associated with high tumor grade, myometrial invasion, lymph node involvement,
      and advanced stage (p < 0.01). HE4 was an independent prognostic factor for
      reduced disease-free survival and overall survival with hazard ratios of 2.96
      (95% confidence interval: 1.18-7.99) and 3.27 (95% confidence interval: 1.18
      9.02), respectively. At recurrence, 75% of the patients had an elevated HE4
      compared to 54% with an elevated CA125. HE4 levels were more frequently elevated
      in patients with distant metastasis compared to local recurrences, 67% and 37%,
      respectively. Serum HE4 detected a recurrence with a median of 126 days earlier
      than clinical confirmation. CONCLUSION: Elevated serum HE4 is an independent risk
      factor for reduced disease-free survival and overall survival. HE4 seems to be
      superior to CA125 in the detection of recurrent disease during follow-up, mainly
      in high-risk endometrial cancer patients who are more prone to distant
      metastasis.

PMID- 29463192
TI  - Home-based exercise for elderly patients with intermittent claudication limited
      by osteoarticular disorders - feasibility and effectiveness of a low-intensity
      programme.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a common cardiovascular
      pathology affecting mobility in elderly. Osteoarticular diseases (ODs),
      responsible for functional limitations and confounding leg symptoms, may
      interfere with exercise therapy. This study evaluates the feasibility and
      effectiveness of a structured home-based exercise programme on rehabilitative
      outcomes in a cohort of elderly PAD patients with and without coexisting ODs.
      PATIENTS AND METHODS: Patients were enrolled from 2002 to 2016 in an exercise
      programme prescribed and controlled at the hospital and based on two daily 10
      minute home walking sessions below the self-selected speed. The presence and
      localization of ODs at baseline were derived from consultation of medical
      documents. The ankle-brachial index and functional outcomes, defined as speed at
      the onset of claudication and attainable maximal speed by an incremental
      treadmill test, were assessed at baseline and discharge. Feasibility was
      determined according to dropout rate, number of visits, duration of the
      programme, and adherence. RESULTS: A total of 1,251 PAD patients were enrolled
      (931 men; 71 +/- 9 years; 0.63 +/- 0.19 ankle-brachial index). Eight hundred
      sixty-four patients were free of ODs (ODfreePAD, 69 %), whereas 387 were affected
      by ODs (ODPAD, 31 %), predominantly located in the spine (72 %). In the logistic
      regression models, the presence of ODs was associated with female sex,
      overweight, sedentary and/or driving professions. At discharge, ODPAD and
      ODfreePAD did not differ in dropout rates (12 % each), programme duration (378 +/
      241 vs. 390 +/- 260 days), number of visits (7 +/- 3 each), and adherence (80 %
      each). Similar improvements for ODPAD and ODfreePAD were observed for the ankle
      brachial index (0.06 +/- 0.12 each), the speed at onset of claudication (0.7 +/-
      0.7 vs. 0.7 +/- 0.8 kmh-1; p = 0.70), and maximal speed (0.4 +/- 0.6 vs. 0.4 +/-
      0.6 kmh-1; p = 0.77). CONCLUSIONS: Equally satisfactory rehabilitative outcomes
      were observed in elderly patients with claudication limited by ODs who completed
      a well-tolerated, low-impact structured exercise programme.

PMID- 29463193
TI  - Quality assessment in Belgian arrhythmology: the Belgian heart rhythm association
      (BeHRA) databases.
AB  - This report presents and discusses, on behalf of the Belgian College of
      Cardiology, the evolution of the peer review process in arrhythmology, focussing
      on pacemaker implantation. Data from the last 22 years are compared. The national
      annual increase in implants is around 1%, clinical patient characteristics
      remained stable over the years while dual chamber pacing was proportionally
      increasing. Analyses of the normalised sick sinus and complete atrioventricular
      block ratios revealed a quite homogenous practice between centres and patient
      district with the only exception of the two more crowded districts. Battery
      longevity and infection rate were also assessed. With an incidence of 1/1000
      device-years follow-up, Belgium remains below accepted European levels.

PMID- 29463194
TI  - The Expression and Prognostic Impact of the PI3K/AKT/mTOR Signaling Pathway in
      Advanced Esophageal Squamous Cell Carcinoma.
AB  - The abnormal phosphatase and tensin homolog expression and activated
      phosphoinositide-3 kinase/Protein kinase B (AKT)/mammalian target of rapamycin
      signaling pathway are involved in the progression of esophageal squamous cell
      carcinoma. By assessing the expression pattern of key components in the
      phosphoinositide-3 kinase/AKT/mammalian target of rapamycin signaling pathway by
      immunohistochemistry in tumor and nontumor esophageal mucosa from patients with
      esophageal squamous cell carcinomas, we aimed to carefully explore the
      relationship between the various protein expressions and clinicopathological
      factors, as well as patient outcome. A total of 145 tumor and 145 nontumor
      samples from patients with esophageal squamous cell carcinoma, collected from
      HuaShan Hospital (Shanghai, China) were evaluated. Clinical characteristics, the
      targeted protein expressions (including phosphatase and tensin homolog,
      phosphoinositide-3 kinase, AKT, p-AKT, mammalian target of rapamycin, p-mTOR,
      p70S6 kinase 1, p-P70S6K1, elongation initiation factor 4E binding protein-1, and
      p-4E-BP1, and survival rate were analyzed. Among them, phosphoinositide-3 kinase,
      AKT, p-AKT, mammalian target of rapamycin, p-mTOR, elongation initiation factor
      4E binding protein-1, p70S6 kinase 1, and p-P70S6K1 proteins were significantly
      upregulated in tumor tissue. Conversely, phosphatase and tensin homolog was
      largely downregulated in tumor tissue, notably in pT3-T4 tumors. Low expression
      of phosphatase and tensin homolog whereas high expression of mammalian target of
      rapamycin signaling components in tumors was closely related to the presence of
      lymph node metastases and advanced TNM stage (all P < .05). Moreover phosphatase
      and tensin homolog, mammalian target of rapamycin, and p70S6 kinase 1 were
      correlated with overall survival as well as p-mTOR was correlated with
      progression-free survival (all P < .05). Overexpression of mammalian target of
      rapamycin was proved to be an independent adverse prognostic factor for overall
      survival in esophageal squamous cell carcinomas. Our results suggest that the
      phosphoinositide-3 kinase/AKT/mammalian target of rapamycin signaling pathway is
      activated in esophageal squamous cell carcinoma, with the low expression of
      phosphatase and tensin homolog and the high expression of the mammalian target of
      rapamycin component proteins (both total and phosphorylated) in tumor tissue. Our
      result might offer a new strategy for specific targeted therapy and prognostic
      assessment in esophageal cancer.

PMID- 29463195
TI  - Physical workload and musculoskeletal disorders in back, shoulders and neck among
      welders.
AB  - This study aimed to determine the effect of the physical workload on the back,
      neck and shoulders of welders. The prevalence of musculoskeletal symptoms was
      assessed using the Nordic questionnaire among 15 welders. The physical workload
      of the neck, back and upper arms was then measured by means of inclinometry as
      the welders were working. The results revealed that the highest prevalence of
      musculoskeletal disorders during the previous 12 months was in the lower back and
      shoulders. The median trunk and neck flexion were significantly associated with
      back and neck pain in welders with symptoms during the past year (p < 0.05).
      Physical exposure in welders with pain was characterized by significantly more
      awkward postures and percentage of time spent with the trunk and neck flexed more
      than 20 degrees . The nature of their work and the design of their workstations
      may be causes of the symptoms they experienced during work.

PMID- 29463196
TI  - Reflection on the Professor-Priming Replication Report.

PMID- 29463197
TI  - Cephalic pancreaticoduodenectomy with preservation of a right coronary artery
      bypass graft using the right gastro-epiploic artery: a case report.
AB  - INTRODUCTION: Pancreatic cancer is a rare disease with a high mortality rate, for
      which complete surgical resection, when possible, is the preferred therapeutic.
      Pancreaticoduodenectomy represents the surgical technique of choice. Abdominal
      surgeons can be faced with the challenge of patients with a history of coronary
      artery bypass graft in which the right gastro-epiploic artery is used. CASE
      REPORT: We report the case of a patient with an adenocarcinoma of the pancreatic
      head, stage IIA, having previously undergone a triple coronary artery bypass, one
      of which being a right gastro-epiploic graft. Our challenge was underlined by the
      necessity of a complete oncological resection through a cephalic
      pancreaticoduodenectomy while preserving the necessary cardiac perfusion via the
      right gastro-epiploic artery. CONCLUSION: We have been able to preserve a right
      gastro-epiploic artery as a coronary bypass during a cephalic
      pancreaticoduodenectomy for a cephalic pancreatic adenocarcinoma. We have
      successfully been able to preserve and re-implant the right gastro-epiploic
      artery to the origin of the gastroduodenal artery while insuring R0 resection of
      the tumor. A coronary artery bypass using the right gastro-epiploic artery should
      therefore not be considered as an obstacle to a Whipple's procedure if total
      oncological resection is obtainable.

PMID- 29463199
TI  - Airborne particulate matter impairs corneal epithelial cells migration via
      disturbing FAK/RhoA signaling pathway and cytoskeleton organization.
AB  - BACKGROUND: Cornea is the outmost structure of the eye and exposed directly to
      the air pollution. However, little is known about the effect of PM2.5 on corneal
      epithelium, which is critical for maintenance of cornea homeostasis and visual
      function. OBJECTIVE: We investigated the influence of PM2.5 exposure on corneal
      epithelial migration and the possible mechanisms involved in the process.
      METHODS: We observed wound healing in mouse model of cornea abrasion, evaluated
      the migration and mobility of cultured corneal epithelial cells with wound
      scratch assay and Transwell migration assay, detected the phosphorylation and
      interaction of FAK/paxillin with immunofluorescence and immunoprecipitation, and
      determined the RhoA activity and actin reorganization, in response to PM2.5
      exposure. RESULTS: Exposure to PM2.5 remarkably inhibited corneal epithelial cell
      migration both in mouse model of corneal abrasion and in cell culture model. We
      found the phosphorylation and interaction of FAK/paxillin, RhoA activity as well
      as actin reorganization were suppressed by PM2.5 exposure. Moreover, formation of
      ROS might play a role in the action of PM2.5. CONCLUSIONS: PM2.5 exposure could
      result in delay of corneal epithelium wound healing by inhibiting cell migration,
      thus more attention should be paid to the potential risk of corneal infection and
      effort should be made to protect eyes against impairment induced by PM2.5.

PMID- 29463198
TI  - A network approach for provisional assay recognition of a Hendra virus antibody
      ELISA: test validation with low sample numbers from infected horses.
AB  - Obtaining statistically sound numbers of sera from Hendra virus (HeV)-infected
      horses is problematic because affected individuals usually die or are euthanized
      before developing a serum antibody response. As a consequence, test validation
      becomes a challenge. Our approach is an extension of OIE principles for
      provisional recognition and included 7 validation panels tested across multiple
      laboratories that provided estimates for test performance characteristics. At a
      0.4 S/P cutoff, 16 of 19 sera from HeV-infected horses gave positive results in
      the HeV soluble G, indirect ELISA (HeVsG iELISA; DSe 84.2% [95% CI: 60.4-96.6%]);
      463 of 477 non-infected horse sera tested negative (DSp 97.1% [95% CI: 95.1
      98.4%]). The HeVsG iELISA eliminated almost all false-positive results from the
      previously used HeV iELISA, with marginally decreased relative sensitivity. Assay
      robustness was evaluated in inter-laboratory and proficiency testing panels. The
      HeVsG iELISA is considered to be fit for purpose for serosurveillance and
      international movement of horses when virus neutralization is used for follow-up
      testing of positive or inconclusive serum samples.

PMID- 29463201
TI  - Effectiveness of GonaCon as an immunocontraceptive in colony-housed cats.
AB  - Objectives Non-surgical contraceptive management of free-roaming cat populations
      is a global goal for public health and humane reasons. The objectives of this
      study were to measure the duration of contraception following a single
      intramuscular injection of a gonadotropin-releasing hormone-based vaccine
      (GonaCon) and to confirm its safe use in female cats living in colony conditions.
      Methods GonaCon (0.5 ml/cat) was administered intramuscularly to 20 intact female
      cats (queens), and saline was administered to 10 queens serving as sham-treated
      controls. Beginning in late February, 4 months after injection, all cats were
      housed with fertile male cats in a simulated colony environment. Time to
      pregnancy, fetal counts and vaccine-elicited injection-site reactions were
      evaluated. Results All control cats (n = 10/10) and 60% (n = 12/20) of vaccinated
      cats became pregnant within 4 months of the introduction of males. Two additional
      vaccinates became pregnant (70%; n = 14/20) within 1 year of treatment. Average
      fetal counts were significantly lower in vaccinated cats than in control cats.
      Vaccinates had a significantly longer ( P = 0.0120) median time to conception
      (212 days) compared with controls (127.5 days). Injection-site reactions ranging
      from swelling to transient granulomatous masses were observed in 45% (n = 9/20)
      of vaccinated cats. Conclusions and relevance A single dose of GonaCon provided
      contraception lasting for a minimum of 1 year in 30% (n = 6/20) of treated cats.
      The level of contraception induced by this GonaCon dose and vaccine lot was not
      sufficiently effective to be recommended for use in free-roaming cats.

PMID- 29463202
TI  - Development, initial validation and reliability testing of a web-based, generic
      feline health-related quality-of-life instrument.
AB  - Objectives The objective of this study was to develop a valid, reliable web
      based, generic feline health-related quality-of-life (HRQoL) questionnaire
      instrument to measure the affective impact of chronic disease. Methods A large
      initial item pool, obtained through interviews with cat owners, was reduced using
      predetermined criteria, survey scores for relevance and clarity, and the ability
      of individual items to discriminate between healthy and sick cats when owners
      completed a prototype questionnaire. Using these data, factor analysis was used
      to derive a scoring algorithm and provide evidence for factorial validity.
      Validity was demonstrated further in a field trial using a 'known groups'
      approach (sick vs healthy cats will have a different HRQoL profile, and the HRQoL
      profile of cats will deteriorate as comorbidities increase). Test-retest
      reliability was assessed using intra-class correlation coefficients (ICC).
      Results In total, 165 items were reduced to 20 and, on the basis of a factor
      analysis that explained 72.3% of the variation in scores input by 71 owners of 30
      healthy and 41 sick cats using the prototype, these were allocated to three
      domains (vitality, comfort and emotional wellbeing [EWB]) with a scoring
      algorithm derived using item loadings. Subsequently, the owners of 36 healthy and
      58 sick cats completed one or two (n = 48) assessments. Median scores (healthy vs
      sick) for all domains were significantly different ( P <0.001), 78% of cats were
      correctly classified as healthy or sick and for comorbidities the correlation
      coefficients were moderate (vitality 0.64; comfort 0.63; EWB 0.50). Test-retest
      reliability was good (ICC vitality 0.635; comfort 0.716; EWB 0.853). Conclusions
      and relevance This study provides initial evidence for the validity and
      reliability of a novel HRQoL instrument to aid the assessment and management of
      chronic diseases of cats.

PMID- 29463203
TI  - Exploring the link between number of years since menopause and metabolic syndrome
      among women in rural China: a cross-sectional observational study.
AB  - The aim of this article was to explore the link between postmenopausal status
      according to years since menopause (YSM) and the prevalence of metabolic syndrome
      (MetS). This survey was conducted from January 2012 to August 2013. A total of
      6022 women (3511, 58.3% were post-menopause) from Rural Northeast China were
      randomly selected and examined. The prevalence of the MetS was significantly
      higher in postmenopausal women (Post-MW) than in premenopausal women (Pre-MW)
      (55.0% vs. 33.1%, p .001). The risk for MetS in Post-MW increased with the number
      of YSM, reaching the peak level in the 5- to 9-year group (OR, 1.55; 95% CI, 1.23
      1.96), and then decreased. The 5- to 9-year group had the highest risk of high
      glucose (OR, 1.48; 95% CI, 1.20-1.83) and high triglycerides (adjusted OR, 1.92;
      95% CI, 1.53-2.41) whereas the risk for abdominal obesity, high BP, and low HDL-C
      was not significantly associated with the number of YSM. These findings suggested
      that, in China, Post-MW with 5-9 YSMs had the highest risk of MetS. YSM can be a
      useful screening tool to identify women at high risk for MetS.

PMID- 29463204
TI  - Intraindividual variability in neurocognitive performance is associated with time
      based prospective memory in older adults.
AB  - INTRODUCTION: Older adults demonstrate poorer prospective memory (PM) performance
      than younger adults, particularly for time-based cues and other strategically
      demanding PM tasks. Intraindividual variability (IIV) in neurocognitive test
      performance is an index of cognitive control that may be related to the execution
      of strategically demanding PM tasks. METHOD: Participants included 194 older
      Australian adults (age 50 to 88 years) who completed the Memory for Intentions
      Screening Test (MIST), the Prospective and Retrospective Memory Questionnaire
      (PRMQ), and clinical measures of executive functions. A measure of naturalistic
      time-based PM was also administered, in which participants were asked to call the
      examiner 24 hours after their appointment to report how many hours they slept.
      IIV was calculated as the mean-adjusted coefficient of variation (CoV) across
      subtests of the Repeatable Battery for the Assessment of Neuropsychological
      Status (RBANS). RESULTS: IIV was significantly associated with time-based PM in
      the laboratory, independent of demographics. Additionally, IIV significantly
      predicted performance on a naturalistic time-based PM trial, independent of
      demographics and chronic medical conditions. IIV was not related to event-based
      laboratory PM or self-reported PM symptoms in daily life. Clinical measures of
      executive functions were similarly associated with time-based PM and the
      naturalistic PM task, but not with event-based PM or subjective PM symptoms.
      CONCLUSIONS: These results indicate that cognitive control, as indexed by IIV in
      neurocognitive performance, may play a role in naturalistic PM, as well as in
      highly strategic, but not automatic, laboratory-based PM among older adults.

PMID- 29463205
TI  - Outcomes of arthroscopic capsular release for the diabetic frozen shoulder in
      Asian patients.
AB  - INTRODUCTION: Diabetic patients have been known to have a higher incidence of
      frozen shoulder. Arthroscopic capsular release has been described for diabetic
      frozen shoulder refractory to non-surgical treatment. We describe our single
      surgeon experience of this procedure done in Asian patients presenting with
      diabetic frozen shoulder. RESULTS: Data were prospectively collected from 25
      patients from 2007 to 2008, who underwent arthroscopic capsular release for
      frozen shoulder with diabetes mellitus. This included the University of
      California-Los Angeles (UCLA) Shoulder Score by an independent observer. Mean
      follow-up duration was 44.3 +/- 22 months with the age of 57.3 +/- 10.9 years at
      the time of surgery. Mean duration of symptoms prior to surgery was 8.9 +/- 7.5
      months. Ten right shoulders and 15 left shoulders were operated on. Arthroscopic
      capsular release was performed in the beach chair position with the aid of a 90
      degrees  electrocautery hook, from the rotator interval to posterior capsule.
      Significant improvement was observed in the UCLA scores post-operatively
      (preoperative total score 15.8 +/- 3.6 vs. post-operative 33.3 +/- 2.5, p <
      0.00), including all domains of pain (3.9 +/- 1.8 vs. 9.4 +/- 0.9, p < 0.00),
      function (4.8 +/- 1.7 vs. 9.4 +/- 1.4, p < 0.00), active forward flexion (2.6 +/-
      0.7 vs. 4.6 +/- 0.6, p < 0.00) and satisfaction (0.0 +/- 0.0 vs. 5.0 +/- 0.0, p <
      0.00). No significant correlation between duration of symptoms and UCLA scores.
      Significant improvement was observed in forward flexion (preoperative 100.4 +/-
      18.8 degrees  vs. post-operative 157.6 +/- 15.9 degrees , p < 0.00) and external
      rotation (preoperative 14.4 +/- 6.34 degrees  vs. post-operative 63.8 +/- 8.3
      degrees , p < 0.00). Although the duration of symptoms correlated significantly
      with preoperative forward flexion ( r = 0.443 and p < 0.027), there was no
      significant correlation with post-operative forward flexion ( r = 0.023 and p <
      0.91). No axillary nerve palsy observed. CONCLUSION: The diabetic frozen shoulder
      can be treated favourably with arthroscopic capsular release and the duration of
      symptoms prior to surgery does not affect the outcomes.

PMID- 29463206
TI  - Endovascular Retrieval of a Migrated TrapEase Inferior Vena Cava Filter From the
      Right Atrium: A Brief Report and Literature Review.
AB  - Intracardiac migration is a rare complication of inferior vena cava filters
      (IVCFs) that poses a significant risk to patients. Both endovascular and surgical
      options exist, although only a few endovascular options are described in the
      literature. This brief report describes the endovascular approach used to
      successfully remove a TrapEase IVCF from the right atrium in a single patient. A
      brief review of the literature is also provided.

PMID- 29463207
TI  - Effects of flexible ureteroscopy on renal blood flow: a prospective evaluation.
AB  - OBJECTIVE: This study aimed to investigate the effects of flexible ureteroscopy
      (F-URS) on renal blood flow using renal Doppler ultrasound (US). MATERIALS AND
      METHOD: Patients undergoing F-URS were scheduled for Doppler US preoperatively
      and postoperatively. Peak systolic velocity (PSV), end-diastolic velocity (EDV),
      resistive index (RI) and pulsatility index (PI) were reported. Technical details,
      operation time, stone characteristics and complications were recorded. Patients
      were grouped as 9.5/11.5-Flex-X2, 10/12-Flex-X2, 10/12-Flex-XC, 12/14-Flex-X2 and
      12/14-Flex-XC, with 28, six, three, seven and two patients in each group,
      respectively. RESULTS: Forty-six patients with a mean age of 41.24 years and
      stone volume of 1685 mm3 were enrolled. The PSV, EDV, PI and RI of renal arteries
      in all groups in preoperative and postoperative periods were similar. Arcuate
      artery measurements in all groups were also similar in preoperative and
      postoperative periods, without any significant difference except in two
      parameters: RI in the 9.5/11.5-Flex-X2 group and PSV in the 12/14-Flex-X2 group.
      The resistive index in the arcuate artery of the 9.5/11.5-Flex-X2 group was
      increased from 0.59 to 0.62 cm/sec postoperatively. The PSV in the arcuate artery
      of the 12/14-Flex-X2 group was decreased from 30.9 to 27.2 cm/sec. Three patients
      had urinary tract infections postoperatively and two had sepsis. CONCLUSION: This
      study suggests that compatible ureteroscope-ureteral access sheath combinations
      with a lumen difference of more than 1.5 Fr can provide safe outcomes in terms of
      renal blood flow. F-URS can safely be performed in terms of renal perfusion and
      complication rates with appropriate equipment and instruments.

PMID- 29463208
TI  - The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant
      prioritization tool.
AB  - BACKGROUND: Prioritization of sequence variants for diagnosis and discovery of
      Mendelian diseases is challenging, especially in large collections of whole
      genome sequences (WGS). Fast, scalable solutions are needed for discovery
      research, for clinical applications, and for curation of massive public variant
      repositories such as dbSNP and gnomAD. In response, we have developed VVP, the
      VAAST Variant Prioritizer. VVP is ultrafast, scales to even the largest variant
      repositories and genome collections, and its outputs are designed to simplify
      clinical interpretation of variants of uncertain significance. RESULTS: We show
      that scoring the entire contents of dbSNP (> 155 million variants) requires only
      95 min using a machine with 4 cpus and 16 GB of RAM, and that a 60X WGS can be
      processed in less than 5 min. We also demonstrate that VVP can score variants
      anywhere in the genome, regardless of type, effect, or location. It does so by
      integrating sequence conservation, the type of sequence change, allele
      frequencies, variant burden, and zygosity. Finally, we also show that VVP scores
      are consistently accurate, and easily interpreted, traits not shared by many
      commonly used tools such as SIFT and CADD. CONCLUSIONS: VVP provides rapid and
      scalable means to prioritize any sequence variant, anywhere in the genome, and
      its scores are designed to facilitate variant interpretation using ACMG and NHS
      guidelines. These traits make it well suited for operation on very large
      collections of WGS sequences.

PMID- 29463209
TI  - Characterisation of Zika virus infection in primary human astrocytes.
AB  - BACKGROUND: The recent Zika virus (ZIKV) outbreak has linked ZIKV with
      microcephaly and other central nervous system pathologies in humans. Astrocytes
      are among the first cells to respond to ZIKV infection in the brain and are also
      targets for virus infection. In this study, we investigated the interaction
      between ZIKV and primary human brain cortical astrocytes (HBCA). RESULTS: HBCAs
      were highly sensitive to representatives of both Asian and African ZIKV lineages
      and produced high viral yields. The infection was associated with limited immune
      cytokine/chemokine response activation; the highest increase of expression,
      following infection, was seen in CXCL-10 (IP-10), interleukin-6, 8, 12, and CCL5
      (RANTES). Ultrastructural changes in the ZIKV-infected HBCA were characterized by
      electron tomography (ET). ET reconstructions elucidated high-resolution 3D images
      of the proliferating and extensively rearranged endoplasmic reticulum (ER)
      containing viral particles and virus-induced vesicles, tightly juxtaposed to
      collapsed ER cisternae. CONCLUSIONS: The results confirm that human astrocytes
      are sensitive to ZIKV infection and could be a source of proinflammatory
      cytokines in the ZIKV-infected brain tissue.

PMID- 29463210
TI  - Barriers to and strategies for addressing the availability, accessibility,
      acceptability and quality of the sexual, reproductive, maternal, newborn and
      adolescent health workforce: addressing the post-2015 agenda.
AB  - BACKGROUND: In a post-2015 development agenda, achieving Universal Health
      Coverage (UHC) for women and newborns will require a fit-for-purpose and fit-to
      practice sexual, reproductive, maternal, adolescent and newborn health (SRMNAH)
      workforce. The aim of this paper is to explore barriers, challenges and solutions
      to the availability, accessibility, acceptability and quality (AAAQ) of SRMNAH
      services and workforce. METHODS: The State of the World's Midwifery report 2014
      used a broad definition of midwifery ("the health services and health workforce
      needed to support and care for women and newborns") and provided information
      about a wide range of SRMNAH workers, including doctors, midwives, nurses and
      auxiliaries. As part of the data collection, 36 out of the 73 participating low-
      and middle-income countries conducted a one-day workshop, involving a range of
      different stakeholders. Participants were asked to discuss barriers to the AAAQ
      of SRMNAH workers, and to suggest strategies for overcoming the identified
      barriers. The workshop was facilitated using a discussion guide, and a rapporteur
      took detailed notes. A content analysis was undertaken using N-Vivo software and
      the AAAQ model as a framework. RESULTS: Across the 36 countries, about 800
      participants attended a workshop. The identified barriers to AAAQ of SRMNAH
      workers included: insufficient size of the workforce and inequity in its
      distribution, lack of transportation, user fees and out of pocket payments. In
      some countries, respondents felt that women mistrusted the workforce, and
      particularly midwives, due to cultural differences, or disrespectful behaviour
      towards service users. Quality of care was undermined by a lack of
      supplies/equipment and inadequate regulation. Against these, countries identified
      a set of solutions including adequate workforce planning supported by a fast and
      equitable deployment system, aligned with the principles of UHC. Acceptability
      and quality could be improved with the provision of respectful care as well as
      strategies to improve education and regulation. CONCLUSIONS: The number and scale
      of the barriers still needing to be addressed in these 36 countries was
      significant. Adequate planning and policies to support the development of the
      SRMNAH workforce and its equitable distribution are a priority. Enabling
      strategies need to be put in place to improve the status and recognition of
      midwives, whose role is often undervalued.

PMID- 29463211
TI  - TEAM-UP for quality: a cluster randomized controlled trial protocol focused on
      preventing pressure ulcers through repositioning frequency and precipitating
      factors.
AB  - BACKGROUND: Pressure ulcers/injuries (PrUs), a critical concern for nursing homes
      (NH), are responsible for chronic wounds, amputations, septic infections, and
      premature deaths. PrUs occur most commonly in older adults and NH residence is a
      risk factor for their development, with at least one of every nine U.S. NH
      residents experiencing a PrU and many NHs having high incidence and prevalence
      rates, in some instances well over 20%. PrU direct treatment costs are greater
      than prevention costs, making prevention-focused protocols critical. Current PrU
      prevention protocols recommend repositioning residents at moderate, high, and
      severe risk every 2 h. The advent of visco-elastic (VE) high-density foam support
      surfaces over the past decade may now make it possible to extend the
      repositioning interval to every 3 or 4 h without increasing PrU development. The
      TEAM-UP (Turn Everyone And Move for Ulcer Prevention) study aims to determine: 1)
      whether repositioning interval can be extended for NH residents without
      compromising PrU incidence and 2) how changes in medical severity interact with
      changes in risk level and repositioning schedule to predict PrU development.
      METHODS: In this proposed cluster randomized study, 9 NHs will be randomly
      assigned to one of three repositioning intervals (2, 3, or 4 h) for a 4-week
      period. Each enrolled site will use a single NH-wide repositioning interval as
      the standard of care for residents at low, moderate, and high risk of PrU
      development (N = 951) meeting the following criteria: minimum 3-day stay, without
      PrUs, no adhesive allergy, and using VE support surfaces (mattresses). An FDA
      cleared patient monitoring system that records position/movement of these
      residents via individual wireless sensors will be used to visually cue staff when
      residents need repositioning and document compliance with repositioning
      protocols. DISCUSSION: This study will advance knowledge about repositioning
      frequency and clinically assessed PrU risk level in relation to PrU incidence and
      medical severity. Outcomes of this research will contribute to future guidelines
      for more precise preventive nursing practices and refinement of PrU prevention
      guidelines. TRIAL REGISTRATION: Clinical Trial Registration: NCT02996331 .

PMID- 29463212
TI  - The genome of Austrofundulus limnaeus offers insights into extreme vertebrate
      stress tolerance and embryonic development.
AB  - BACKGROUND: The annual killifish Austrofundulus limnaeus inhabits ephemeral ponds
      in northern Venezuela, South America, and is an emerging extremophile model for
      vertebrate diapause, stress tolerance, and evolution. Embryos of A. limnaeus
      regularly experience extended periods of desiccation and anoxia as a part of
      their natural history and have unique metabolic and developmental adaptations.
      Currently, there are limited genomic resources available for gene expression and
      evolutionary studies that can take advantage of A. limnaeus as a unique model
      system. RESULTS: We describe the first draft genome sequence of A. limnaeus. The
      genome was assembled de novo using a merged assembly strategy and was annotated
      using the NCBI Eukaryotic Annotation Pipeline. We show that the assembled genome
      has a high degree of completeness in genic regions that is on par with several
      other teleost genomes. Using RNA-seq and phylogenetic-based approaches, we
      identify several candidate genes that may be important for embryonic stress
      tolerance and post-diapause development in A. limnaeus. Several of these genes
      include heat shock proteins that have unique expression patterns in A. limnaeus
      embryos and at least one of these may be under positive selection. CONCLUSION:
      The A. limnaeus genome is the first South American annual killifish genome made
      publicly available. This genome will be a valuable resource for comparative
      genomics to determine the genetic and evolutionary mechanisms that support the
      unique biology of annual killifishes. In a broader context, this genome will be a
      valuable tool for exploring genome-environment interactions and their impacts on
      vertebrate physiology and evolution.

PMID- 29463213
TI  - MCM family in HCC: MCM6 indicates adverse tumor features and poor outcomes and
      promotes S/G2 cell cycle progression.
AB  - BACKGROUND: Minichromosome Maintenance family (MCMs), as replication licensing
      factors, is involved in the pathogenesis of tumors. Here, we investigated the
      expression of MCMs and their values in hepatocellular carcinoma (HCC). METHODS:
      MCMs were analyzed in 105 samples including normal livers (n = 15), cirrhotic
      livers (n = 40), HCC (n = 50) using quantitative polymerase chain reaction (qPCR)
      (Cohort 1). Significantly up-regulated MCMs were verified in 102 HCC and matched
      peritumoral livers using PCR (Cohort 2), and the correlations with clinical
      features and outcomes were determined. In addition, the focused MCMs were
      analyzed in parallel immunohistochemistry of 345 samples on spectrum of
      hepatocarcinogenesis (Cohort 3) and queried for the potential specific role in
      cell cycle. RESULTS: MCM2-7, MCM8 and MCM10 was significantly up-regulated in HCC
      in Cohort 1. In Cohort 2, overexpression of MCM2-7, MCM8 and MCM10 was verified
      and significantly correlated with each other. Elevated MCM2, MCM6 and MCM7 were
      associated with adverse tumor features and poorer outcomes. In Cohort 3, MCM6
      exhibited superior HCC diagnostic performance compared with MCM2 and MCM7 (AUC:
      0.896 vs. 0.675 and 0.771, P < 0.01). Additionally, MCM6 other than MCM2 and MCM7
      independently predicted poorer survival in 175 HCC patients. Furthermore,
      knockdown of MCM6 caused a delay in S/G2-phase progression as evidenced by down
      regulation of CDK2, CDK4, CyclinA, CyclinB1, CyclinD1, and CyclinE in HCC cells.
      CONCLUSIONS: We analyze MCMs mRNA and protein levels in tissue samples during
      hepatocarcinogenesis. MCM6 is identified as a driver of S/G2 cell cycle
      progression and a potential diagnostic and prognostic marker in HCC.

PMID- 29463215
TI  - Association of differential miRNA expression with hepatic vs. peritoneal
      metastatic spread in colorectal cancer.
AB  - BACKGROUND: Though peritoneal carcinomatosis reflects a late stage of colorectal
      cancer (CRC), only few patients present with synchronous or metachronous liver
      metastases alongside their peritoneal carcinomatosis. It is hypothesized that
      this phenomenon may be causally linked to molecular characteristics of the
      primary CRC. This study used miRNA profiling of primary CRC tissue either
      metastasized to the liver, to the peritoneum or not metastasized at all thus to
      identify miRNAs potentially associated with defining the site of metastatic
      spread in CRC. METHODS: Tissue of the primary tumor stemming from CRC patients
      diagnosed for either liver metastasis (LM; n = 10) or peritoneal carcinomatosis
      (PER; n = 10) was analyzed in this study. Advanced CRC cases without metastasis
      (M0; n = 3) were also included thus to select on those miRNAs most potentially
      associated with determining metastatic spread in general. miRNA profiling of 754
      different miRNAs was performed in each group. MiRNAs being either differentially
      expressed comparing PER and LM or even triple differentially expressed (PER vs.
      LM vs. M0) were identified. Differentially expressed miRNAs were further
      validated by in silico and functional analysis. RESULTS: Comparative analysis
      identified 41 miRNAs to be differentially expressed comparing primary tumors
      metastasized to the liver as opposed to those spread to the peritoneum. A set of
      31 miRNAs was significantly induced in primary tumors that spread to the
      peritoneum (PER), while the remaining 10 miRNAs were found to be repressed. Out
      of these 41 miRNAs a number of 25 miRNAs was triple-differentially expressed
      (i.e. differentially expressed comparing LM vs. PER vs. M0). The latter underwent
      in silico analysis. Finally, we demonstrated that miR-31 down-regulated c-MET in
      DLD-1 colon cancer cells. CONCLUSIONS: This study demonstrates that CRC primary
      tumors spread to the peritoneum vs. metastasized to the liver display
      significantly different miRNA profiles. Larger patient cohorts will be needed to
      validate whether determination of e.g. miR-31 may aid to predict the course of
      disease and whether this may help to create individualized follow up or treatment
      protocols. To determine whether certain miRNAs may be involved in regulating the
      metastatic potential of CRC, functional studies will be essential.

PMID- 29463214
TI  - Genome mining for peptidases in heat-tolerant and mesophilic fungi and putative
      adaptations for thermostability.
AB  - BACKGROUND: Peptidases (EC 3.4) consist of a large group of hydrolytic enzymes
      that catalyze the hydrolysis of proteins accounting for approximately 65% of the
      total worldwide enzyme production. Peptidases from thermophilic fungi have
      adaptations to high temperature that makes them adequate for biotechnological
      application. In the present study, we profiled the genomes of heat-tolerant fungi
      and phylogenetically related mesophilic species for genes encoding for peptidases
      and their putative adaptations for thermostability. RESULTS: We generated an
      extensive catalogue of these enzymes ranging from 241 to 820 peptidase genes in
      the genomes of 23 fungi. Thermophilic species presented the smallest number of
      peptidases encoding genes in relation to mesophilic species, and the peptidases
      families with a greater number of genes were the most affected. We observed
      differences in peptidases in thermophilic species in comparison to mesophilic
      counterparts, at (i) the genome level: a great reduction in the number of
      peptidases encoding genes that harbored a higher number of copies; (ii) in the
      primary protein structure: shifts in proportion of single or groups of amino
      acids; and (iii) in the three-dimensional structure: reduction in the number of
      internal cavities. Similar results were reported for extremely thermophilic
      proteins, but here we show for the first time that several changes also occurred
      on the moderate thermophilic enzymes of fungi. In regards to the amino acids
      composition, peptidases from thermophilic species in relation to the mesophilic
      ones, contained a larger proportion of Ala, Glu, Gly, Pro, Arg and Val residues
      and a lower number of Cys, His, Ile, Lys, Met, Asn, Gln, Ser, Thr and Trp
      residues (P < 0.05). Moreover, we observed an increase in the proportion of
      hydrophobic and charged amino acids and a decrease in polar amino acids.
      CONCLUSIONS: Although thermophilic fungi present less genes encoding for
      peptidases, these have adaptations that could play a role in thermal resistance
      from genome to protein structure level.

PMID- 29463216
TI  - Long non-coding RNA HOTAIR polymorphism and susceptibility to cancer: an updated
      meta-analysis.
AB  - BACKGROUND: An increasing number of publications are drawing attention to the
      associations between six common polymorphisms in HOX transcript anti-sense RNA
      (HOTAIR) and the risk of cancers, while these results have been controversial and
      inconsistent. We conducted an up-to-date meta-analysis to pool eligible studies
      and to further explore the possible relationships between HOTAIR polymorphisms
      (rs920778, rs7958904, rs12826786, 4,759,314, rs874945, and rs1899663) and cancer
      risk. METHODS: A systematic retrieval was conducted up to 1 July 2017 in the
      PubMed, Web of Science, and CNKI databases. Eighteen eligible publications
      including 45 case-control studies with 58,601subjects were enrolled for assessing
      the associations between the 6 polymorphisms in HOTAIR and cancer risk. Pooled
      odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed to reveal the
      polymorphisms and susceptibility to cancer. All the statistical analyses were
      performed using STATA 11.0 software. RESULTS: The pooled analyses detected
      significant associations between the rs920778 polymorphism and increased
      susceptibility to cancer in recessive, dominant, allelic, homozygous, and
      heterozygous models. For the rs7958904 polymorphism, we obtained the polymorphism
      significantly decreased susceptibility to overall cancer risk among five genetic
      models rather than recessive and homozygous models. For the rs12826786
      polymorphism, we identified it significantly increased susceptibility to cancer
      risk in all genetic models rather than heterozygous models. However, no
      significant association was found between the rs1899663, rs874945, and rs4759314
      polymorphisms and susceptibility of cancer. CONCLUSION: These findings of the
      meta-analysis suggest that HOTAIR polymorphism may contribute to cancer
      susceptibility.

PMID- 29463217
TI  - Elucidation of cross-species proteomic effects in human and hominin bone proteome
      identification through a bioinformatics experiment.
AB  - BACKGROUND: The study of ancient protein sequences is increasingly focused on the
      analysis of older samples, including those of ancient hominins. The analysis of
      such ancient proteomes thereby potentially suffers from "cross-species proteomic
      effects": the loss of peptide and protein identifications at increased
      evolutionary distances due to a larger number of protein sequence differences
      between the database sequence and the analyzed organism. Error-tolerant proteomic
      search algorithms should theoretically overcome this problem at both the peptide
      and protein level; however, this has not been demonstrated. If error-tolerant
      searches do not overcome the cross-species proteomic issue then there might be
      inherent biases in the identified proteomes. Here, a bioinformatics experiment is
      performed to test this using a set of modern human bone proteomes and three
      independent searches against sequence databases at increasing evolutionary
      distances: the human (0 Ma), chimpanzee (6-8 Ma) and orangutan (16-17 Ma)
      reference proteomes, respectively. RESULTS: Incorrectly suggested amino acid
      substitutions are absent when employing adequate filtering criteria for mutable
      Peptide Spectrum Matches (PSMs), but roughly half of the mutable PSMs were not
      recovered. As a result, peptide and protein identification rates are higher in
      error-tolerant mode compared to non-error-tolerant searches but did not recover
      protein identifications completely. Data indicates that peptide length and the
      number of mutations between the target and database sequences are the main
      factors influencing mutable PSM identification. CONCLUSIONS: The error-tolerant
      results suggest that the cross-species proteomics problem is not overcome at
      increasing evolutionary distances, even at the protein level. Peptide and protein
      loss has the potential to significantly impact divergence dating and proteome
      comparisons when using ancient samples as there is a bias towards the
      identification of conserved sequences and proteins. Effects are minimized between
      moderately divergent proteomes, as indicated by almost complete recovery of
      informative positions in the search against the chimpanzee proteome (~90%, 6-8
      Ma). This provides a bioinformatic background to future phylogenetic and
      proteomic analysis of ancient hominin proteomes, including the future description
      of novel hominin amino acid sequences, but also has negative implications for the
      study of fast-evolving proteins in hominins, non-hominin animals, and ancient
      bacterial proteins in evolutionary contexts.

PMID- 29463218
TI  - Effects of cardiorespiratory fitness and weight status on knowledge of physical
      activity and fitness, attitude toward physical education, and physical activity.
AB  - BACKGROUND: The purpose of this study was to examine the effects of
      cardiorespiratory fitness and weight status on knowledge of physical activity and
      fitness (PAF knowledge), attitude toward physical education (PE), and physical
      activity. METHODS: A total of 343 middle school students participated in the
      study (Age: M/SD = 12.76/.94, ranging from 11 to 14 years old). PE MetricsTM was
      used to measure PAF knowledge, and Attitude toward Physical Education
      Questionnaire and Youth Activity Profile were used to measure attitude, physical
      activity and sedentary behavior. Fitness and weight status were assessed using
      FitnessGram and converted to in Healthy Fitness Zone (HFZ) or Not in HFZ.
      RESULTS: Two-way multivariate analyses of covariance (MANCOVA; gender and grade
      as covariates) showed a significant group effect for cardiorespiratory fitness
      (LambdaPilla = .07, F4,255 = 5.03, p = .001, [Formula: see text] = .07) but not
      for weight status (p = .57). PAF knowledge (F1,258 = 9.49, p < .01, [Formula: see
      text]= .04), attitude (F1,258 = 4.45, p < .05, [Formula: see text]= .02) and
      sedentary behavior (F1,258 = 6.89, p < .01, [Formula: see text]= .03) all favored
      the HFZ group. CONCLUSIONS: The findings reinforce the importance of promoting
      cardiorespiratory fitness in middle school PE as students acquire attitude,
      knowledge, and behaviors needed for active-living.

PMID- 29463220
TI  - Interferon alpha-2a treatment for refractory Behcet uveitis in Korean patients.
AB  - BACKGROUND: To evaluate therapeutic outcomes of interferon alpha-2a (IFNalpha2a)
      treatment in patients with Behcet's disease who were refractory to
      immunosuppressive agents. METHODS: This retrospective case series reviewed the
      medical records of 5 patients with refractory Behcet uveitis from January 2011 to
      February 2017. IFNalpha2a was administered at a dose of 3 million IU 3 times per
      week. Clinical response, relapse rate, and change of visual acuity were
      evaluated. RESULTS: The mean age of patients was 39.60 +/- 9.21 years, and the
      median treatment duration was 6 months. Four of the 5 patients (80%) presented
      with responses to IFNalpha2a without any uveitis attack during the treatment
      period. The mean number of uveitis attacks/year per patient during the treatment
      was 0.40 +/- 0.89. The mean log of the Minimum Angle of Resolution visual acuity
      improved from 1.44 +/- 0.38 at baseline to 1.02 +/- 0.58 at the final follow up.
      CONCLUSIONS: IFNalpha2a is an effective therapy for Behcet uveitis refractory to
      conventional immunosuppressants in Korean patients.

PMID- 29463219
TI  - Perceived acceptability and preferences for low-intensity early activity
      interventions of older hospitalized medical patients exposed to bed rest: a cross
      sectional study.
AB  - BACKGROUND: Hospitalized older patients spend most of their time in bed, putting
      them at risk of experiencing orthostatic intolerance. Returning persons to their
      usual upright activity level is the most effective way to prevent orthostatic
      intolerance but some older patients have limited activity tolerance, supporting
      the need for low-intensity activity interventions. Consistent with current
      emphasis on patient engagement in intervention design and evaluation, this study
      explored older hospitalized patients' perceived acceptability of, and preference
      for, two low-intensity early activity interventions (bed-to-sitting and sitting
      to-walking), and characteristics (gender, illness severity, comorbidity,
      illnesses and medications with orthostatic effects, and baseline functional
      capacity) associated with perceived acceptability and preference. METHODS: A
      convenience sample was recruited from in-patient medical units of two hospitals
      in Ontario, Canada and included 60 cognitively intact adults aged 65+ who were
      admitted for a medical condition within the past 72 h, spent >= 24 consecutive
      hours on a stretcher or in bed, presented with >= 2 chronic diseases, understood
      English, and were able to ambulate before admission. A cross-sectional
      observational design was used. Participants were presented written and oral
      descriptions and a 2-min video of each intervention. The sequence of the
      interventions' presention was randomized. Following the presentation, a research
      nurse administered measures of perceived acceptability and preference, and
      collected health and demographic data. Perceived acceptability and preference for
      the interventions were measured using the Treatment Acceptability and Preferences
      Scale. Illness severity was measured using the Modified Early Warning Score.
      Comorbidity was assessed with the Age Adjusted Charlson Comorbidity Scale and the
      Cumulative Illness Rating Scale - for Geriatrics. Baseline functional capacity
      was measured using the Duke Activity Status Index. RESULTS: Participants'
      perceived acceptability of both interventions clustered above the scale midpoint.
      Most preferred the sitting-to-walking intervention (n = 26; 43.3%). While none of
      the patient characteristics were associated with intervention acceptability,
      illness severity (odds ratio = 1.9, p = 0.04) and medications with orthostatic
      effects (odds ratio = 9.9, p = 0.03) were significantly associated with
      intervention preference. CONCLUSIONS: The interventions examined in this study
      were found to be acceptable to older adults, supporting future research examining
      their feasibility and effectiveness.

PMID- 29463221
TI  - Determinants of antenatal depression and postnatal depression in Australia.
AB  - BACKGROUND: Depression is a leading source of morbidity and health loss in
      Australian women. This study investigates the determinants of antenatal
      depressive symptoms and postnatal depressive symptoms in an Australian
      population, including people from culturally and linguistically diverse (CALD)
      backgrounds. METHOD: The study used a retrospective cohort of mothers of all live
      births in public health facilities in 2014 (N = 17,564) within South Western
      Sydney Local Health District and Sydney Local Health District in New South Wales,
      Australia. Prevalence of antenatal and postnatal depressive symptoms were
      estimated for the cohort. Multivariate logistic regression models were conducted
      to investigate the sociodemographic, psychological and health service
      determinants of antenatal and postnatal depressive symptoms, measured using the
      Edinburgh Postnatal Depression Scale (EPDS). RESULTS: The prevalence of antenatal
      and postnatal depressive symptoms was 6.2% and 3.3% of the cohort, respectively.
      Significant risk factors for maternal depressive symptoms during pregnancy were,
      a lack of partner support, history of intimate partner violence, being from the
      CALD population and low socioeconomic status. Self-reported antenatal depressive
      symptoms were strongly associated with postnatal depressive symptoms. Risk
      factors for postnatal depressive symptoms were similar to those for antenatal
      depressive symptoms, as well as assisted delivery. CONCLUSION: Factors relating
      to demographic and psychosocial disadvantage were associated with subsequent
      antenatal and postnatal depressive symptoms in New South Wales, Australia. Our
      study suggests that screening for probable depression and timely referral for
      expert assessment of at-risk mothers may be an effective strategy to improve
      maternal mental health outcomes.

PMID- 29463222
TI  - Filtration based assessment of CTCs and CellSearch(r) based assessment are both
      powerful predictors of prognosis for metastatic breast cancer patients.
AB  - BACKGROUND: The assessment of circulating tumor cells (CTCs) has been shown to
      enable monitoring of treatment response and early detection of metastatic breast
      cancer (MBC) recurrence. The aim of this study was to compare a well-established
      CTC detection method based on immunomagnetic isolation with a new, filtration
      based platform. METHODS: In this prospective study, two 7.5 ml blood draws were
      obtained from 60 MBC patients and CTC enumeration was assessed using both the
      CellSearch(r) and the newly developed filtration-based platform. We analyzed the
      correlation of CTC-positivity between both methods and their ability to predict
      prognosis. Overall survival (OS) was calculated and Kaplan-Meier curves were
      estimated with thresholds of >=1 and >=5 detected CTCs. RESULTS: The CTC
      positivity rate of the CellSearch(r) system was 56.7% and of the filtration-based
      platform 66.7%. There was a high correlation of CTC enumeration obtained with
      both methods. The OS for patients without detected CTCs, regardless of the method
      used, was significantly higher compared to patients with one or more CTCs (p <
      0.001). The median OS of patients with no CTCs vs. >= 1 CTC assessed by
      CellSearch(r) was 1.83 years (95% CI: 1.63-2.02) vs. 0.74 years (95% CI: 0.51
      1.52). If CTCs were detected by the filtration-based method the median OS times
      were 1.88 years (95% CI: 1.74-2.03) vs. 0.59 years (95% CI: 0.38-0.80).
      CONCLUSIONS: The newly established EpCAM independently filtration-based system is
      a suitable method to determine CTC counts for MBC patients. Our study confirms
      CTCs as being strong predictors of prognosis in our population of MBC patients.

PMID- 29463223
TI  - Breast cancer subtype discordance: impact on post-recurrence survival and
      potential treatment options.
AB  - BACKGROUND: Recent studies have shown that breast cancer subtype can change from
      the primary tumour to the recurrence. Discordance between primary and recurrent
      breast cancer has implications for further treatment and ultimately prognosis.
      The aim of the study was to determine the rate of change between primary and
      recurrence of breast cancer and to assess the impact of these changes on survival
      and potential treatment options. METHODS: Patient demographics were collected on
      those who underwent surgery for breast cancer between 2001 and 2014 and had a
      recurrence with biopsy results and pathology scoring of both the primary and
      recurrence. RESULTS: One hundred thirty two consecutive patients were included.
      There were 31 (23.5%) changes in subtype. Discordance occurred most frequently in
      luminal A breast cancer (n = 20), followed by triple negative (n = 4), luminal B
      (n = 3) and HER2 (n = 3). Patients who changed from luminal A to triple negative
      (n = 18) had a significantly worse post-recurrence survival (p < 0.05) with
      overall survival approaching significance (p = 0.064) compared to concordant
      luminal A cases (n = 46). Overall receptor discordance rates were: estrogen
      receptor 20.4% (n = 27), progesterone receptor 37.7% (n = 50) and HER2 3% (n =
      4). Loss of estrogen receptor and progesterone receptor was more common than gain
      (21 vs. 6 (p = 0.04) and 44 vs. 6 (p = 0.01) respectively). Nine patients (6.8%)
      gained receptor status potentially impacting treatment options. CONCLUSION:
      Discordance in subtype and receptor status occurs between primary and recurrent
      breast cancer, ultimately affecting survival and potentially impacting treatment
      options.

PMID- 29463224
TI  - A spatiotemporal mixed model to assess the influence of environmental and
      socioeconomic factors on the incidence of hand, foot and mouth disease.
AB  - BACKGROUND: As a common infectious disease, hand, foot and mouth disease (HFMD)
      is affected by multiple environmental and socioeconomic factors, and its
      pathogenesis is complex. Furthermore, the transmission of HFMD is characterized
      by strong spatial clustering and autocorrelation, and the classical statistical
      approach may be biased without consideration of spatial autocorrelation. In this
      paper, we propose to embed spatial characteristics into a spatiotemporal additive
      model to improve HFMD incidence assessment. METHODS: Using incidence data (6439
      samples from 137 monitoring district) for Shandong Province, China, along with
      meteorological, environmental and socioeconomic spatial and spatiotemporal
      covariate data, we proposed a spatiotemporal mixed model to estimate HFMD
      incidence. Geo-additive regression was used to model the non-linear effects of
      the covariates on the incidence risk of HFMD in univariate and multivariate
      models. Furthermore, the spatial effect was constructed to capture spatial
      autocorrelation at the sub-regional scale, and clusters (hotspots of high risk)
      were generated using spatiotemporal scanning statistics as a predictor. Linear
      and non-linear effects were compared to illustrate the usefulness of non-linear
      associations. Patterns of spatial effects and clusters were explored to
      illustrate the variation of the HFMD incidence across geographical sub-regions.
      To validate our approach, 10-fold cross-validation was conducted. RESULTS: The
      results showed that there were significant non-linear associations of the
      temporal index, spatiotemporal meteorological factors and spatial environmental
      and socioeconomic factors with HFMD incidence. Furthermore, there were strong
      spatial autocorrelation and clusters for the HFMD incidence. Spatiotemporal
      meteorological parameters, the normalized difference vegetation index (NDVI), the
      temporal index, spatiotemporal clustering and spatial effects played important
      roles as predictors in the multivariate models. Efron's cross-validation R2 of
      0.83 was acquired using our approach. The spatial effect accounted for 23% of the
      R2, and notable patterns of the posterior spatial effect were captured.
      CONCLUSIONS: We developed a geo-additive mixed spatiotemporal model to assess the
      influence of meteorological, environmental and socioeconomic factors on HFMD
      incidence and explored spatiotemporal patterns of such incidence. Our approach
      achieved a competitive performance in cross-validation and revealed strong
      spatial patterns for the HFMD incidence rate, illustrating important implications
      for the epidemiology of HFMD.

PMID- 29463225
TI  - Glycolysis is essential for chemoresistance induced by transient receptor
      potential channel C5 in colorectal cancer.
AB  - BACKGROUND: Elevated intracellular Ca2+ ([Ca2+] i ) level could lead to [Ca2+] i
      overload and promote apoptosis via different pathways. In our previously study,
      up-regulated expression of transient receptor potential canonical channel (TRPC5)
      was proven to increase [Ca2+] i level, and resulted in chemoresistance whereas
      not apoptosis in human colorectal cancer (CRC) cells. The ATP-dependent
      homeostatic maintenance of resting [Ca2+] i should be important in this process.
      Increased glycolysis was found to be an important adenosine triphosphate (ATP)
      source in cancer. This study aimed to explore the potential mechanism of aerobic
      glycolysis in transient receptor potential channel TRPC5 induced chemoresistance.
      METHODS: In this study, we examined glucose transporter 1 (GLUT1) expression,
      glucose consumption and celluar ATP production to determine glycolytic activity.
      Real-time PCR and western blot were analyzed to determine TRPC5 expression at the
      mRNA and protein levels in human CRC cells (HCT-8, LoVo), and fluorouracil (5-Fu)
      resistant CRC cells (HCT-8/5-Fu, LoVo/5-Fu). 3-bromopyruvate (3-BP) and 2-Deoxy-D
      glucose (2DG) were used to inhibit glycolysis. Glycolytic activity, intracellular
      Ca2+ ([Ca2+] i ) and the half maximal inhibitory concentration of 5-Fu (5-Fu
      IC50) were measured. Western blot was analyzed to determine cleaved Caspase-3
      protein level. Flow cytometry was performed to detect the apoptosis rates.
      Immunohistochemistry staining was performed to determine TRPC5 and GLUT1
      expression level in human CRC tissues. RESULTS: Overproduced of TRPC5 and
      increased glycolysis were found in HCT-8/5-Fu and LoVo/5-Fu than in HCT-8 and
      LoVo cells. Compared to HCT-8 cells, the HCT-8/5-Fu cells showed higher [Ca2+] i
      levels which decreased after treated with TRPC5-specific shRNA. Furthemore,
      inhibition of glycolysis resulted in decreased ATP production, elevation of
      [Ca2+] i level and cleaved caspase-3, increased apoptotic cells rate, and a
      remarkable reversal of 5-Fu resistance in HCT-8/5-Fu cells, while showed no
      effect in HCT-8 cells. BAPTA-AM, a [Ca2+] i chelator, could reduce the elevation
      of cleaved caspase-3 and increased apoptotic cells rate due to glycolysis
      inhibition. Advanced CRC patients with high expression of TRPC5/GLUT1 displayed
      poorer chemotherapy outcome, and notably, the significant association between
      high TRPC5 expression and chemoresistance is GLUT1 expression level dependent.
      CONCLUSIONS: We demonstrated the essential role of glycolysis in TRPC5 induced
      chemoresistance in human CRC cells via maintaining [Ca2+] i homeostasis.

PMID- 29463226
TI  - Acquired distance esotropia associated with myopia in the young adult.
AB  - BACKGROUND: To describe the clinical features of acquired progressive esotropia,
      with a larger angle at distance than near, associated with myopia in young
      adults. METHODS: Eleven adults (ages ranging from 18 to 37 years) with constant
      or intermittent horizontal diplopia at distance were recruited. Subjective
      refraction, ocular alignment, fusional amplitudes and horizontal eye movements
      were measured at distance and near. RESULTS: Distance esotropia varied from 20 to
      60 prism diopters (PD). At near, the esotropic deviation ranged from 10 to 30 PD.
      Spherical equivalents (SE) of the right eye ranged from - 3.50 to - 8.25 diopters
      (D) while SE of the left eye ranged from - 0.375 to - 7.25 D. Ten of the eleven
      patients presented with constant diplopia at distance. Horizontal ductions and
      versions were full in all patients. The pathological report of seven patients who
      underwent lateral rectus resection showed that there were no muscle fibres, but
      rather, collagenous fibres. CONCLUSIONS: This unusual sub-type of strabismus is a
      benign entity with slow progression that can occur in young adults with myopia.
      The cause of this condition is still unknown, and may be related to long periods
      of near work.

PMID- 29463227
TI  - Evaluating different breast tumor progression models using screening data.
AB  - BACKGROUND: Mammography screening is used to detect breast cancer at an early
      treatable stage, reducing breast cancer mortality. Traditionally, breast cancer
      has been seen as a disease with only progressive lesions, and here we examine the
      validity of this assumption by testing if incidence levels after introducing
      mammography screening can be reproduced assuming only progressive tumors.
      METHODS: Breast cancer incidence data 1990-2009 obtained from the initially
      screened Norwegian counties (Akershus, Oslo, Rogaland and Hordaland) was
      included, covering the time-period before, during and after the introduction of
      mammography screening. From 1996 women aged 50-69 were invited for biennial
      public screening. Using estimates of tumor growth and screening sensitivity based
      on pre-screening and prevalence screening data (1990-1998), we simulated
      incidence levels during the following period (1999-2009). RESULTS: The simulated
      incidence levels during the period with repeated screenings were markedly below
      the observed levels. The results were robust to changes in model parameters.
      Adjusting for hormone replacement therapy use, we obtained levels closer to the
      observed levels. However, there was still a marked gap, and only by assuming some
      tumors that undergo regressive changes or enter a markedly less detectable state,
      was our model able to reproduce the observed incidence levels. CONCLUSIONS:
      Models with strictly progressive tumors are only able to partly explain the
      changes in incidence levels observed after screening introduction in the
      initially screened Norwegian counties. More complex explanations than a time
      shift in detection of future clinical cancers seem to be needed to reproduce the
      incidence trends, questioning the basis for many over-diagnosis calculations. As
      data are not randomized, similar studies in other populations are wanted to
      exclude effect of unknown confounders.

PMID- 29463228
TI  - Preliminary qualification of a novel, hypoxic-based radiologic signature for
      trans-arterial chemoembolization in hepatocellular carcinoma.
AB  - BACKGROUND: Survival advantage following trans-arterial chemoembolization (TACE)
      is variable in patients with hepatocellular carcinoma (HCC). We combined pre-TACE
      radiologic features to derive a novel prognostic signature in HCC. METHODS: A
      multi-institutional dataset of 98 patients was generated from two retrospective
      cohorts from United Kingdom (65%) and Italy (36%). The prognostic impact of a
      number baseline imaging parameters was assessed and factors significant on
      univariate analysis were combined to create a novel radiologic signature on
      multivariable analyses predictive of overall survival (OS) following TACE.
      RESULTS: Median OS was 15.4 months. Tumour size > 7 cm (p < 0.001), intra-tumour
      necrosis (ITN) (p = 0.02) and arterial ectatic neovascularisation (AEN) (p =
      0.03) emerged as individual prognostic factors together with radiologic response
      (p < 0.001) and elevated alpha-fetoprotein (AFP) (p = 0.01). Combination of
      tumour size > 7 cm, ITN and AEN identified patients with poor prognosis (p <
      0.001). CONCLUSIONS: We identified a coherent signature based on commonly
      available imaging biomarkers likely to be reflective of differential patterns of
      relative hypoxia and neovascularisation. Large tumours displaying AEN and ITN are
      characterised by a shorter survival after TACE.

PMID- 29463229
TI  - Metastatic cardiac tumors: from clinical presentation through diagnosis to
      treatment.
AB  - BACKGROUND: To evaluate the prevalence of metastatic tumors involving the
      myocardium and study their presentation in order to increase awareness to their
      existence. METHODS: Pathological reports from Sheba Medical Center (Israel,
      January 1, 2010 through December 31, 2015) and medical records from The Institute
      for Cardiovascular Diseases of Vojvodina, Sremska Kamenica (Serbia, 23 years
      period) were screened for cases of metastatic cardiac tumors. Medical,
      radiological and pathological data of identified cases was retrieved and
      reviewed. RESULTS: Out of thousands of registered cardiac surgeries we found less
      than a dozen cases of metastatic cardiac tumors classified as melanoma,
      carcinomas of lung, colon and kidney and sarcomas of uterine origin. We found
      that metastatic cardiac tumors comprised 15.8% of all the cardiac tumors.
      CONCLUSIONS: Metastatic cardiac tumors are extremely rare. As new diagnostic
      technologies and improved survival of oncological patients may increase the
      incidence of metastatic cardiac tumors in the future, awareness to their
      existence and knowledge of their presentation are key factors in their timely
      recognition.

PMID- 29463230
TI  - Vendor-based restrictions on pesticide sales to prevent pesticide self-poisoning 
      a pilot study.
AB  - BACKGROUND: In South Asia, up to 20% of people ingesting pesticides for self
      poisoning purchase the pesticide from a shop with the sole intention of self
      harm. Individuals who are intoxicated with alcohol and/or non-farmers represent
      72% of such high-risk individuals. We aimed to test the feasibility and
      acceptability of vendor-based restrictions on pesticide sales for such high-risk
      individuals. METHODS: We conducted a pilot study in 14 (rural = 7, urban = 7)
      pesticide shops in Anuradhapura District of Sri Lanka. A two-hour training
      program was delivered to 28 pesticide vendors; the aim of the training was to
      help vendors recognize and respond to customers at high risk of pesticide self
      poisoning. Knowledge and attitudes of vendors towards preventing access to
      pesticides for self-poisoning at baseline and in a three month follow-up was
      evaluated by questionnaire. Vendors were interviewed to explore the practice
      skills taught in the training and their assessment of the program. RESULTS: The
      scores of knowledge and attitudes of the vendors significantly increased by 23%
      (95% CI 15%-32%, p < 0.001) and by 16% (95% CI 9%-23%, p < 0.001) respectively in
      the follow-up. Fifteen (60%) vendors reported refusing sell pesticides to a high
      risk person (non-farmer or intoxicated person) in the follow-up compared to three
      (12%) at baseline. Vendors reported that they were aware from community feedback
      that they had prevented at least seven suicide attempts. On four identified
      occasions, vendors in urban shops had been unable to recognize the self-harming
      intention of customers who then ingested the pesticide. Only 2 (8%) vendors were
      dissatisfied with the training and 23 (92%) said they would recommend it to other
      vendors. CONCLUSIONS: Our study suggests that vendor-based sales restriction in
      regions with high rates of self-poisoning has the potential to reduce access to
      pesticides for self-poisoning. A large-scale study of the effectiveness and
      sustainability of this approach is needed.

PMID- 29463231
TI  - Prevalence and correlates of non-adherence to immunosuppressants and to health
      behaviours in patients after kidney transplantation in Brazil - the ADHERE BRAZIL
      multicentre study: a cross-sectional study protocol.
AB  - BACKGROUND: Non-adherence to immunosuppressive therapy is a prevalent risk factor
      for poor clinical and after kidney transplantation (KT), and has contributed to
      the lack of improvement in long-term graft survival over the past decade.
      Understanding the multilevel correlates and risk factors of non-adherence is
      crucial to determine the optimal level for planning interventions, namely at the
      patient, health care provider, KT centre, and health care system level. Brazil,
      having the largest public transplantation program in the world and with regional
      differences regarding access to health services and service implementation, is in
      a unique position to study this multilevel approach. Therefore, the Adhere Brazil
      Study (ADHERE BRAZIL) was designed to assess the prevalence and variability of
      non-adherence to immunosuppressants and to health behaviours among adult KT
      recipients in Brazil, and to assess the multilevel correlates of non-adherence to
      immunosuppressive medication. We describe the rationale, design, and methodology
      of the ADHERE BRAZIL study. METHODS/DESIGN: This is an observational, cross
      sectional, multicentre study that includes 20 Brazilian KT centres. A stratified
      sampling approach is used, based on strata, with the following characteristics
      considered: geographical region and transplant activity (number of KTs per year).
      A random sample of patients (proportional to the size of the centre within each
      stratum) is selected from each centre. The prevalence of different health
      behaviours is assessed through self-report. The assessment of multilevel
      correlates of non-adherence is guided by the ecological model that considers
      factors at the level of the patient, health-care professional, and transplant
      centre, using established instruments or instruments developed for this study.
      Data will be collected over an 18-month period, with information obtained during
      the regular follow-up visits to the transplant outpatient clinic and directly
      entered into the Research Electronic Data Capture (RedCap) system. Data entry is
      performed by a trained professional who is part of the transplant team. The data
      collection began in December 2015. DISCUSSION: This multicentre study is the
      first to evaluate multilevel correlates of non-adherence in KT patients and will
      provide a reliable estimate of non-adherence in Brazilian KT patients. TRIAL
      REGISTRATION: ClinicalTrials.gov on 10/10/2013, NCT02066935 .

PMID- 29463232
TI  - Finding RNA structure in the unstructured RBPome.
AB  - BACKGROUND: RNA-binding proteins (RBPs) play vital roles in many processes in the
      cell. Different RBPs bind RNA with different sequence and structure
      specificities. While sequence specificities for a large set of 205 RBPs have been
      reported through the RNAcompete compendium, structure specificities are known for
      only a small fraction. The main limitation lies in the design of the RNAcompete
      technology, which tests RBP binding against unstructured RNA probes, making it
      difficult to infer structural preferences from these data. We recently developed
      RCK, an algorithm to infer sequence and structural binding models from RNAcompete
      data. The set of binding models enables, for the first time, a large-scale
      assessment of RNA structure in the RBPome. RESULTS: We re-validate and uncover
      the role of RNA structure in the RPBome through novel analysis of the largest
      scale dataset to date. First, we show that RNA structure exists in presumably
      unstructured RNA probes and that its variability is correlated with RNA-binding.
      Second, we examine the structural binding preferences of RBPs and discover an
      overall preference to bind RNA loops. Third, we significantly improve protein
      binding prediction using RNA structure, both in vitro and in vivo. Lastly, we
      demonstrate that RNA structural binding preferences can be inferred for new
      proteins from solely their amino acid content. CONCLUSIONS: By counter
      intuitively demonstrating through our analysis that we can predict both the RNA
      structure of and RBP binding to these putatively unstructured RNAs, we transform
      a compendium of RNA-binding proteins into a valuable resource for structure-based
      binding models. We uncover the important role RNA structure plays in protein-RNA
      interaction for hundreds of RNA-binding proteins.

PMID- 29463233
TI  - Efficacy of a bivalent killed whole-cell cholera vaccine over five years: a re
      analysis of a cluster-randomized trial.
AB  - BACKGROUND: Oral cholera vaccine (OCV) is a feasible tool to prevent or mitigate
      cholera outbreaks. A better understanding of the vaccine's efficacy among
      different age groups and how rapidly its protection wanes could help guide
      vaccination policy. METHODS: To estimate the level and duration of OCV efficacy,
      we re-analyzed data from a previously published cluster-randomized, double-blind,
      placebo controlled trial with five years of follow-up. We used a Cox proportional
      hazards model and modeled the potentially time-dependent effect of age categories
      on both vaccine efficacy and risk of infection in the placebo group. In addition,
      we investigated the impact of an outbreak period on model estimation. RESULTS:
      Vaccine efficacy was 38% (95% CI: -2%,62%) for those vaccinated from ages 1 to
      under 5 years old, 85% (95% CI: 67%,93%) for those 5 to under 15 years, and 69%
      (95% CI: 49%,81%) for those vaccinated at ages 15 years and older. Among adult
      vaccinees, efficacy did not appear to wane during the trial, but there was
      insufficient data to assess the waning of efficacy among child vaccinees.
      CONCLUSIONS: Through this re-analysis we were able to detect a statistically
      significant difference in OCV efficacy when the vaccine was administered to
      children under 5 years old vs. children 5 years and older. The estimated
      efficacies are more similar to the previously published analysis based on the
      first two years of follow-up than the analysis based on all five years. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier NCT00289224.

PMID- 29463234
TI  - Tuberculosis treatment outcome and predictors in northern Ethiopian prisons: a
      five-year retrospective analysis.
AB  - BACKGROUND: The prison situations are notorious for causing interruptions of
      tuberculosis (TB) treatment and occurrence of unfavorable outcomes. In Ethiopian
      prisons, though TB treatment programs exist, treatment outcome results and
      factors contributing to unsuccessful outcome are not well documented. In this
      study, we assessed the treatment outcome of TB cases and identified risk factors
      for unsuccessful outcome in northern Ethiopian prisons. METHODS: A retrospective
      record review was conducted for all prisoners diagnosed with TB between September
      2011 and August 2015. Outcome variables were defined following WHO guidelines.
      RESULTS: Out of the 496 patients, 11.5% were cured, 68% completed treatment, 2.5%
      were lost to follow-up, 1.6% were with a treatment failure, 1.4% died, and 15%
      were transferred out. All transferred out or released prisoners were not
      appropriately linked to health facilities and might be lost to treatment follow
      up. The overall treatment success rate (TSR) of the 5 years was 94% among the
      patients who were not transferred out. The odds of unsuccessful outcome were 4.68
      times greater among re-treatment cases compared to the newly treated cases. The
      year of treatment was also associated with variations in TSR; those treated
      during the earlier year were more likely to have unsuccessful outcome. Sputum non
      conversion at the second-month check-up was strongly associated with unsuccessful
      outcome among the smear-positive cases. CONCLUSIONS: The mean TSR of the
      prisoners in the study prisons was quite satisfactory when gauged against the
      target level set by the End TB Strategy. However, the lack of appropriate linkage
      and tracking systems for those prisoners transferred or released before their
      treatment completion would have a negative implication for the national TB
      control program as such patients might interrupt their treatment and develop drug
      resistant TB. Being in a re-treatment regimen and sputum non-conversion at the
      second-month check-up were significantly associated with unsuccessful treatment
      outcome among the all forms of and smear-positive TB cases, respectively.

PMID- 29463235
TI  - Glucose, lipids and gamma-glutamyl transferase measured before prostate cancer
      diagnosis and secondly diagnosed primary tumours: a prospective study in the
      Swedish AMORIS cohort.
AB  - BACKGROUND: Improvements in detection and treatment of prostate cancer (PCa)
      translate into more men living with PCa, who are therefore potentially at risk of
      a secondly diagnosed primary tumour (SDPTs). Little is known about potential
      biochemical mechanisms linking PCa with the occurrence of SDPTs. The current
      study aims to investigate serum biomarkers of glucose and lipid metabolism and
      gamma-glutamyl transferase (GGT) measured prior to PCa diagnosis and their
      association with the occurrence of SDPTS. METHODS: From the Swedish AMORIS
      cohort, we selected all men diagnosed with PCa between 1996 and 2011, with at
      least one of the five biomarkers of interest (glucose, fructosamine,
      triglycerides, total cholesterol (TC), GGT) measured on average 16 years before
      PCa diagnosis (n = 10,791). Multivariate Cox proportional hazards models were
      used to determine hazard ratios (HR) for risk of SDPTs (overall and subtypes) by
      levels of the five biomarkers. Effect modification of treatment was assessed.
      RESULTS: 811 SDPTS were diagnosed during a median follow-up time of 5 years.
      Elevated levels of triglycerides (HR: 1.37, 95%CI: 1.17-1.60), TC (HR: 1.22,
      95%CI: 1.04-1.42) and GGT (HR: 1.32, 95%CI: 1.02-1.71) were associated with an
      increased risk of SDPTs. Risk of SDPTs subtypes varied by biomarkers. CONCLUSION:
      Elevated levels of biomarkers of lipid metabolism and GGT measured prior to PCa
      diagnosis were associated with an increased risk of SDPTs, suggesting a potential
      common biochemical background for development of PCa and SDPTs.

PMID- 29463236
TI  - Rapid symptomatic relief of HER2-positive gastric cancer leptomeningeal
      carcinomatosis with lapatinib, trastuzumab and capecitabine: a case report.
AB  - BACKGROUND: Gastric cancer patients with widespread metastasis, especially
      meningeal metastases, have an extremely prognosis and limited therapeutic
      choices. CASE PRESENTATION: We reported the case of a 39-year-old male patient
      with HER2-positive gastric cancer with bone and meningeal metastases. He
      presented with multiple bone metastases and received 3 cycles of docetaxel plus
      S1. However, he complained with headache and imaging examinations revealed
      leptomeningeal carcinomatosis. FISH revealed that tumor cells in the
      cerebrospinal fluid were HER-positive. Herceptin was added to the regimen, but
      the symptoms were not relieved, the patient suffered from dizziness and nausea.
      The chemotherapy regimen was switched d to lapatinib (orally at 1250 mg/day,
      every day), capecitabine (orally at 1000 mg/m2, bid for 2 weeks, followed by a 1
      week rest interval, as 1 cycle) and Herceptin (390 mg/3 weeks). After 3 weeks of
      the new treatment, all the symptoms relieved. The clinical complete response was
      maintained for 3 months. CONCLUSIONS: Lapatinib/Capecitabine combination therapy
      is an alternative treatment strategy for leptomeningeal carcinomatosis of HER2
      positive gastric cancer in which trastuzumab and/or chemotherapy essentially has
      no effect.

PMID- 29463237
TI  - Inhibition of autophagy sensitizes cancer cells to Photofrin-based photodynamic
      therapy.
AB  - BACKGROUND: Accumulating evidence suggest that autophagy plays a pivotal role in
      various anticancer therapies, including photodynamic therapy (PDT), acting as a
      pro-death or pro-survival mechanism in a context-dependent manner. Therefore, we
      aimed to determine the role of autophagy in Photofrin-based PDT. METHODS: In
      vitro cytotoxic/cytostatic effects of PDT were evaluated with crystal violet cell
      viability assay. Autophagy induction was analyzed by immunoblotting and
      immunofluorescence using anti-LC3 antibody. Autophagy was inhibited by shRNA
      mediated ATG5 knockdown or CRISPR/Cas9-mediated ATG5 knockout. Apoptosis was
      assessed by flow cytometry analysis of propidium iodide and anexin V-positive
      cells as well as by detection of cleaved PARP and caspase 3 proteins using
      immunoblotting. Protein carbonylation was evaluated by the 2,4
      dinitrophenylhydrazine (DNPH) method. RESULTS: Photofrin-PDT leads to robust
      autophagy induction in two cancer cell lines, Hela and MCF-7. shRNA-mediated
      knockdown of ATG5 only partially blocks autophagic response and only marginally
      affects the sensitivity of Hela and MCF-7 cells to PDT. ATG5 knockout in HeLa
      cell line utilizing CRISPR/Cas9 genome editing results in increased PDT-mediated
      cytotoxicity, which is accompanied by an enhanced apoptotic response and
      increased accumulation of carbonylated proteins. CONCLUSIONS: Altogether, these
      observations imply that autophagy contributes to Photofrin-PDT resistance by
      enabling clearance of carbonylated and other damaged proteins. Therefore,
      autophagy inhibition may serve as a strategy to improve PDT efficacy.

PMID- 29463238
TI  - Characterization and heterologous expression of the neoabyssomicin/abyssomicin
      biosynthetic gene cluster from Streptomyces koyangensis SCSIO 5802.
AB  - BACKGROUND: The deep-sea-derived microbe Streptomyces koyangensis SCSIO 5802
      produces neoabyssomicins A-B (1-2) and abyssomicins 2 (3) and 4 (4).
      Neoabyssomicin A (1) augments human immunodeficiency virus-1 (HIV-1) replication
      whereas abyssomicin 2 (3) selectively reactivates latent HIV and is also active
      against Gram-positive pathogens including methicillin-resistant Staphylococcus
      aureus (MRSA). Structurally, neoabyssomicins A-B constitute a new subtype within
      the abyssomicin family and feature unique structural traits characteristic of
      extremely interesting biosynthetic transformations. RESULTS: In this work, the
      biosynthetic gene cluster (BGC) for the neoabyssomicins and abyssomicins,
      composed of 28 opening reading frames, was identified in S. koyangensis SCSIO
      5802, and its role in neoabyssomicin/abyssomicin biosynthesis was confirmed via
      gene inactivation and heterologous expression experiments. Bioinformatics and
      genomics analyses enabled us to propose a biosynthetic pathway for
      neoabyssomicin/abyssomicin biosynthesis. Similarly, a protective export system by
      which both types of compounds are secreted from the S. koyangensis producer was
      identified, as was a four-component ABC transporter-based import system central
      to neoabyssomicin/abyssomicin biosynthesis. Furthermore, two regulatory genes,
      abmI and abmH, were unambiguously shown to be positive regulators of
      neoabyssomicin/abyssomicin biosynthesis. Consistent with their roles as positive
      regulatory genes, the overexpression of abmI and abmH (independent of each other)
      was shown to improve neoabyssomicin/abyssomicin titers. CONCLUSIONS: These
      studies provide new insight into the biosynthesis of the abyssomicin class of
      natural products, and highlight important exploitable features of its BGC for
      future efforts. Elucidation of the neoabyssomicin/abyssomicin BGC now enables
      combinatorial biosynthetic initiatives aimed at improving both the titers and
      pharmaceutical properties of these important natural products-based drug leads.

PMID- 29463239
TI  - Spatial modelling of malaria cases associated with environmental factors in South
      Sumatra, Indonesia.
AB  - BACKGROUND: Malaria, a parasitic infection, is a life-threatening disease in
      South Sumatra Province, Indonesia. This study aimed to investigate the spatial
      association between malaria occurrence and environmental risk factors. METHODS:
      The number of confirmed malaria cases was analysed for the year 2013 from the
      routine reporting of the Provincial Health Office of South Sumatra. The cases
      were spread over 436 out of 1613 villages. Six potential ecological predictors of
      malaria cases were analysed in the different regions using ordinary least square
      (OLS) and geographically weighted regression (GWR). The global pattern and
      spatial variability of associations between malaria cases and the selected
      potential ecological predictors was explored. RESULTS: The importance of
      different environmental and geographic parameters for malaria was shown at global
      and village-level in South Sumatra, Indonesia. The independent variables
      altitude, distance from forest, and rainfall in global OLS were significantly
      associated with malaria cases. However, as shown by GWR model and in line with
      recent reviews, the relationship between malaria and environmental factors in
      South Sumatra strongly varied spatially in different regions. CONCLUSIONS: A more
      in-depth understanding of local ecological factors influencing malaria disease as
      shown in present study may not only be useful for developing sustainable regional
      malaria control programmes, but can also benefit malaria elimination efforts at
      village level.

PMID- 29463240
TI  - Patient's and health care provider's perspectives on music therapy in palliative
      care - an integrative review.
AB  - BACKGROUND: The use of music as therapy in multidisciplinary end-of-life care
      dates back to the 1970s and nowadays music therapy (MT) is one of the most
      frequently used complementary therapy in in-patient palliative care in the US.
      However existing research investigated music therapy's potential impact mainly
      from one perspective, referring to either a quantitative or qualitative paradigm.
      The aim of this review is to provide an overview of the users' and providers'
      perspectives on music therapy in palliative care within one research article.
      METHODS: A systematic literature search was conducted using several databases
      supplemented with a hand-search of journals between November 1978 and December
      2016. Inclusion criteria were: Music therapy with adults in palliative care
      conducted by a certified music therapist. Both quantitative and qualitative
      studies in English, German or a Scandinavian language published in peer reviewed
      journals were included. We aimed to identify and discuss the perspectives of both
      patients and health care providers on music therapy's impact in palliative care
      to forward a comprehensive understanding of it's effectiveness, benefits and
      limitations. We investigated themes mentioned by patients within qualitative
      studies, as well as commonly chosen outcome measures in quantitative research. A
      qualitative approach utilizing inductive content analysis was carried out to
      analyze and categorize the data. RESULTS: Twelve articles, reporting on nine
      quantitative and three qualitative research studies were included. Seven out of
      the nine quantitative studies investigated pain as an outcome. All of the
      included quantitative studies reported positive effects of the music therapy.
      Patients themselves associated MT with the expression of positive as well as
      challenging emotions and increased well-being. An overarching theme in both types
      of research is a psycho-physiological change through music therapy. CONCLUSIONS:
      Both quantitative as well as qualitative research showed positive changes in
      psycho-physiological well-being. The integration of the users' and providers'
      perspectives within future research applicable for example in mixed-methods
      designs is recommended.

PMID- 29463242
TI  - Overproduction, purification, and characterization of nanosized polyphosphate
      bodies from Synechococcus sp. PCC 7002.
AB  - BACKGROUND: Inorganic polyphosphate bodies (PPB) have recently been linked to a
      variety of functions in mammalian cells. To improve the yield of PPB from
      Synechococcus sp. PCC 7002 and characterize its form, in this study, a
      recombinant plasmid containing a polyphosphate kinase (ppk) gene was generated
      and transformed into Synechococcus sp. PCC 7002. RESULTS: PPB separated by
      Sephadex G-100 was characterized and added to polarized human intestinal
      epithelial (Caco-2) cells, and the absorption effect was assessed. The ppk gene
      was stably expressed by induction with 1 MUM nickel, and the resulting PPB yield
      from Synechococcus sp. PCC 7002 cells increased by 89.66%. Transmission electron
      microscopy and dynamic light scattering analyses showed that PPB from these cells
      were nanosized, ranging from a few to approximately 100 nanometres in diameter.
      PPB can be taken up by Caco-2 cells and are mainly distributed around lipid
      droplets. CONCLUSIONS: We determined that PPB can be overproduced in
      Synechococcus sp. PCC 7002 and that the resulting PPB were well absorbed by Caco
      2 cells. Microalgae provide a promising "cell factory" for PPB production.

PMID- 29463241
TI  - Decreasing proportion of Anopheles darlingi biting outdoors between long-lasting
      insecticidal net distributions in peri-Iquitos, Amazonian Peru.
AB  - BACKGROUND: In Loreto Department, Peru, a successful 2005-2010 malaria control
      programme (known as PAMAFRO) included massive distribution of long-lasting
      insecticidal nets (LLINs). Additional local distribution of LLINs occurred in
      individual villages, but not between 2012 and 2015. A 2011-2012 study of the
      primary regional malaria vector Anopheles darlingi detected a trend of increased
      exophagy compared with pre-PAMAFRO behaviour. For the present study, An. darlingi
      were collected in three villages in Loreto in 2013-2015 to test two hypotheses:
      (1) that between LLIN distributions, An. darlingi reverted to pre-intervention
      biting behaviour; and, (2) that there are separate sub-populations of An.
      darlingi in Loreto with distinct biting behaviour. RESULTS: In 2013-2015 An.
      darlingi were collected by human landing catch during the rainy and dry seasons
      in the villages of Lupuna and Cahuide. The abundance of An. darlingi varied
      substantially across years, villages and time periods, and there was a twofold
      decrease in the ratio of exophagic:endophagic An. darlingi over the study period.
      Unexpectedly, there was evidence of a rainy season population decline in An.
      darlingi. Plasmodium-infected An. darlingi were detected indoors and outdoors
      throughout the night, and the monthly An. darlingi human biting rate was
      correlated with the number of malaria cases. Using nextRAD genotyping-by
      sequencing, 162 exophagic and endophagic An. darlingi collected at different
      times during the night were genotyped at 1021 loci. Based on model-based and non
      model-based analyses, all genotyped An. darlingi belonged to a homogeneous
      population, with no evidence for genetic differentiation by biting location or
      time. CONCLUSIONS: This study identified a decreasing proportion of exophagic An.
      darlingi in two villages in the years between LLIN distributions. As there was no
      evidence for genetic differentiation between endophagic and exophagic An.
      darlingi, this shift in biting behaviour may be the result of behavioural
      plasticity in An. darlingi, which shifted towards increased exophagy due to
      repellence by insecticides used to impregnate LLINs and subsequently reverted to
      increased endophagy as the nets aged. This study highlights the need to target
      vector control interventions to the biting behaviour of local vectors, which,
      like malaria risk, shows high temporal and spatial heterogeneity.

PMID- 29463243
TI  - Anacardic acid inhibits pancreatic cancer cell growth, and potentiates
      chemotherapeutic effect by Chmp1A - ATM - p53 signaling pathway.
AB  - BACKGROUND: Pancreatic cancer is one of the leading causes of cancer related
      death and its incidence has risen steadily. Although anticancer drugs have been
      developed based on the new molecular findings, the drugs have produced
      unsatisfactory results due to toxicity and resistance. Thus, a complementary
      therapeutic intervention is urgently needed for pancreatic cancer patients.
      METHODS: The aim of this study was to assess the potential therapeutic effect of
      Anacardic acid on pancreatic cancer in vitro and elucidate its underlying
      mechanisms. Human pancreatic cancer cells were treated with Anacardic acid and
      assessed for the cytotoxic effect using MTT and spheroid formation assays. Using
      the same methods, the synergy between Anacardic acid and 5-Fluorouracil or
      Gemcitabine was determined. To elucidate the underlying molecular mechanisms,
      Western blot analysis and immunocytochemistry were performed on cancer cells
      treated with Anacardic acid alone or in combination with 5-Fluorouracil or
      Gemcitabine. Chromatin Modifying Protein 1A (Chmp1A), Ataxia Telangiectasia
      Mutated (ATM), and p53 were the primary signaling molecules examined. In
      addition, Chmp1A was silenced with shRNA to examine the necessity of Chmp1A for
      the anticancer effect of Anacardic acid, 5-Fluorouracil, or Gemcitabine. RESULTS:
      Anacardic acid induced an anticancer effect in pancreatic cancer cell lines in a
      dose dependent manner, and increased the cytotoxicity of 5-Fluorouracil or
      Gemcitabine in MTT cell viability assays. In spheroid formation assays, spheroids
      formed were smaller in size and in number upon Anacardic acid treatment compared
      to control. Mechanistically, Anacardic acid exerted its anticancer activity via
      the activation of Chmp1A, ATM, and p53. Interestingly, 5-Fluorouracil and
      Gemcitabine also induced an increase in Chmp1A protein level, suggesting that
      Chmp1A might mediate the cytotoxic action of chemotherapeutics. Silencing
      experiments indicate that Chmp1A is required for the action of Anacardic acid,
      but not for 5-Fluorouracil or Gemcitabine. CONCLUSIONS: Our data suggests that
      Anacardic Acid might be a promising complementary supplement to slow the
      initiation or progression of pancreatic cancer.

PMID- 29463244
TI  - A single-center retrospective study of factors related to the effects of
      intravenous glucocorticoid therapy in moderate-to-severe and active thyroid
      associated ophthalmopathy.
AB  - BACKGROUND: Intravenous glucocorticoids (ivGC) have been recommended as a first
      line treatment of moderate-to-severe and active thyroid-associated ophthalmopathy
      (TAO). However, not all patients are responsive to ivGC. The identification of
      potential factors used to predict their efficacy and the selection of suitable
      patients have both been lacking. METHODS: It was a single center retrospective
      study. Potential factors related to the effects of ivGC were analyzed using
      logistic regression in 90 consecutive patients with moderate-to-severe and active
      TAO, who received 4.5 g ivGC therapy. Response was defined as the achievement of
      at least three points of the overall response. RESULTS: Fifty-two (57.8%)
      patients showed a positive response to ivGC therapy. Significant correlations
      were observed between the effects of ivGC and pretreatment clinical activity
      score (CAS), duration of eye symptoms, and restoration of euthyroidism. The two
      latter factors were both independent. The duration of eye symptoms was negatively
      correlated with the effects of ivGC, with an odds ratio (OR) of 0.984 (p =
      0.012). Restoration of euthyroidism (OR = 3.282, p = 0.039) and pretreatment CAS
      (OR = 1.653, p < 0.01) were both positively correlated with the effects of ivGC.
      The diagnostic accuracy of the duration of eye symptoms was <=13 months (p =
      0.000), with a specificity of 76.9%, and sensitivity of 65.8%. The diagnostic
      accuracy of the pretreatment CAS was more than 2.5 (p = 0.000), with a
      specificity of 61.5% and sensitivity of 80.5%. Besides, a multi-variables
      prediction model were established as well, which was better in the forecasting
      aspect with an area under curve of 0.784 (p = 0.000). CONCLUSIONS: The duration
      of eye symptoms and restoration of euthyroidism are independent factors that are
      associated with the effects of ivGC. The following practical implications were
      inferred: firstly, the shorter the duration of eye symptoms, the more favorable
      the effects of ivGC therapy. Thus, prompt diagnosis and treatment (within 13
      months) is important. Secondly, the restoration of euthyroidism improves the
      efficacy of ivGC. Thirdly, hope the multi-variables prediction model can be
      applied to clinical therapy in the future.

PMID- 29463245
TI  - Fatigue in chronically critically ill patients following intensive care -
      reliability and validity of the multidimensional fatigue inventory (MFI-20).
AB  - BACKGROUND: Fatigue often occurs as long-term complication in chronically
      critically ill (CCI) patients after prolonged intensive care treatment. The
      Multidimensional Fatigue Inventory (MFI-20) has been established as valid
      instrument to measure fatigue in a wide range of medical illnesses. Regarding the
      measurement of fatigue in CCI patients, the psychometric properties of the MFI-20
      have not been investigated so far. Thus, the present study examines reliability
      and validity of the MFI-20 in CCI patients. METHODS: A convenience sample of n =
      195 patients with Critical Illness Polyneuropathy (CIP) or Myopathy (CIM) were
      recruited via personal contact within four weeks (t1) following the transfer from
      acute care ICU to post-acute ICU at a large rehabilitation hospital. N = 113
      (median age 61.1 yrs., 72.6% men) patients were again contacted via telephone
      three (t2) and six (t3) months following the transfer to post-acute ICU. The MFI
      20, the Euro-Quality of Life (EQ-5D-3 L) and the Structured Clinical Interview
      for the Diagnostic and Statistical Manual of mental disorders DSM-IV (SCID-I)
      were applied within this prospective cohort study. RESULTS: The internal
      consistency Cronbach's alpha was adequate for the MFI-total and all but the
      subscale Reduced Motivation (RM) (range: .50-.91). Item-to-total correlations
      (range: .22-.80) indicated item redundancy for the subscale RM. Confirmatory
      Factor analyses (CFAs) revealed poor model fit for the original 5-factor model of
      the MFI-20 (t2/t3, Confirmatory Fit Index, CFI = .783/ .834; Tucker-Lewis Index,
      TLI = .751/ .809; Root Mean Square Error of Approximation, RMSEA = .112/ .103).
      Among the alternative models (1-, 2-, 3-factor models), the data best fit to a 3
      factor solution summarizing the highly correlated factors General -/ Physical
      Fatigue/ Reduced Activity (GF/ PF/ RA) (t2/ t3, CFI = .878/ .896, TLI = .846/
      .869, RMSEA = .089/ .085, 90% Confidence Interval .073-.104/ .066-.104). The MFI
      total score significantly correlated with the health-related quality of life
      (range: -.65-(-).66) and the diagnosis of major depression (range: .27-.37).
      CONCLUSIONS: In the present sample of CCI patients, a reliable and valid factor
      structure of the MFI-20 could not be ascertained. Especially the subscale RM
      should be revised. Since the factors GF, PF and RA cannot be separated from each
      other and the unclear factorial structure in the present sample of CCI patients,
      the MFI-20 is not recommended for use in this context. TRIAL REGISTRATION: German
      Clinical Trials Registration DRKS00003386 . Registered 13 December 2011,
      retrospectively registered.

PMID- 29463247
TI  - Hormonal and environmental signals guiding stomatal development.
AB  - Stomata are pores on plant epidermis that facilitate gas exchange and water
      evaporation between plants and the environment. Given the central role of stomata
      in photosynthesis and water-use efficiency, two vital events for plant growth,
      stomatal development is tightly controlled by a diverse range of signals. A
      family of peptide hormones regulates stomatal patterning and differentiation. In
      addition, plant hormones as well as numerous environmental cues influence the
      decision of whether to make stomata or not in distinct and complex manners. In
      this review, we summarize recent findings that reveal the mechanism of these
      three groups of signals in controlling stomatal formation, and discuss how these
      signals are integrated into the core stomatal development pathway.

PMID- 29463248
TI  - Lactate promotes specific differentiation in bovine granulosa cells depending on
      lactate uptake thus mimicking an early post-LH stage.
AB  - BACKGROUND: The LH-induced folliculo-luteal transformation is connected with
      alterations of the gene expression profile in cells of the granulosa layer. It
      has been described that hypoxic conditions occur during luteinization, thus
      favoring the formation of L-lactate within the follicle. Despite being a product
      of anaerobic respiration, L-lactate has been shown to act as a signaling molecule
      affecting gene expression in neuronal cells. During the present study, we tested
      the hypothesis that L-lactate may influence differentiation of follicular
      granulosa cells (GC). METHODS: In a bovine granulosa cell culture model effects
      of L- and D-lactate, of increased glucose concentrations and of the lactate
      transport inhibitor UK5099 were analyzed. Steroid hormone production was analyzed
      by RIA and the abundance of key transcripts was determined by quantitative real
      time RT-PCR. RESULTS: L-lactate decreased the production of estradiol and
      significantly affected selected genes of the folliculo-luteal transition as well
      as genes of the lactate metabolism. CYP19A1, FSHR, LHCGR were down-regulated,
      whereas RGS2, VNN2, PTX3, LDHA and lactate transporters were up-regulated. These
      effects could be partly or completely reversed by pre-treatment of the cells with
      UK5099. The non-metabolized enantiomer D-lactate had even more pronounced effects
      on gene expression, whereas increased glucose concentrations did not affect
      transcript abundance. CONCLUSIONS: In summary, our data suggest that L-lactate
      specifically alters physiological and molecular characteristics of GC. These
      effects critically depend on L-lactate uptake, but are not triggered by increased
      energy supply. Further, we could show that L-lactate has a positive feedback on
      the lactate metabolism. Therefore, we hypothesize that L-lactate acts as a
      signaling molecule in bovine and possibly other monovular species supporting
      differentiation during the folliculo-luteal transformation.

PMID- 29463249
TI  - Continued in vitro cefazolin susceptibility in methicillin-susceptible
      Staphylococcus aureus.
AB  - OBJECTIVES: In vitro trends of cefazolin and ceftriaxone susceptibilities from
      pediatric clinical isolates of methicillin-susceptible Staphylococcus aureus
      (MSSA) between 2011 and 2016 were analyzed for surveillance. METHODS: Our
      laboratory continues to use agar disk diffusion for staphylococcal
      susceptibilities applying Clinical Laboratory Standard Institute's 2012
      breakpoints. RESULTS: A total of 3992 MSSA clinical isolates in the last 6 years
      were analyzed for their in vitro cefazolin and ceftriaxone susceptibilities.
      While all MSSA isolates exhibited cefazolin susceptibilities within the
      "susceptible" zone range, there have been a proportion of isolates with
      ceftriaxone susceptibilities falling in "intermediate" zones, ranging from 2.6%
      in 2011 to 8.3% in 2016. CONCLUSIONS: Cefazolin continues to be the recommended
      agent for MSSA treatment at our institution, reflected by the finding that only
      2% (6/321) of patients who received ceftriaxone as definitive therapy for MSSA
      bacteremia during the study period. We have confirmed the cefoxitin-predicted
      MSSA susceptibility to cefazolin, but have found concerning drifts in ceftriaxone
      susceptibilities by continued in vitro monitoring over the last 6 years.

PMID- 29463246
TI  - Next-generation, personalised, model-based critical care medicine: a state-of-the
      art review of in silico virtual patient models, methods, and cohorts, and how to
      validation them.
AB  - Critical care, like many healthcare areas, is under a dual assault from
      significantly increasing demographic and economic pressures. Intensive care unit
      (ICU) patients are highly variable in response to treatment, and increasingly
      aging populations mean ICUs are under increasing demand and their cohorts are
      increasingly ill. Equally, patient expectations are growing, while the economic
      ability to deliver care to all is declining. Better, more productive care is thus
      the big challenge. One means to that end is personalised care designed to manage
      the significant inter- and intra-patient variability that makes the ICU patient
      difficult. Thus, moving from current "one size fits all" protocolised care to
      adaptive, model-based "one method fits all" personalised care could deliver the
      required step change in the quality, and simultaneously the productivity and
      cost, of care. Computer models of human physiology are a unique tool to
      personalise care, as they can couple clinical data with mathematical methods to
      create subject-specific models and virtual patients to design new, personalised
      and more optimal protocols, as well as to guide care in real-time. They rely on
      identifying time varying patient-specific parameters in the model that capture
      inter- and intra-patient variability, the difference between patients and the
      evolution of patient condition. Properly validated, virtual patients represent
      the real patients, and can be used in silico to test different protocols or
      interventions, or in real-time to guide care. Hence, the underlying models and
      methods create the foundation for next generation care, as well as a tool for
      safely and rapidly developing personalised treatment protocols over large virtual
      cohorts using virtual trials. This review examines the models and methods used to
      create virtual patients. Specifically, it presents the models types and
      structures used and the data required. It then covers how to validate the
      resulting virtual patients and trials, and how these virtual trials can help
      design and optimise clinical trial. Links between these models and higher order,
      more complex physiome models are also discussed. In each section, it explores the
      progress reported up to date, especially on core ICU therapies in glycemic,
      circulatory and mechanical ventilation management, where high cost and frequency
      of occurrence provide a significant opportunity for model-based methods to have
      measurable clinical and economic impact. The outcomes are readily generalised to
      other areas of medical care.

PMID- 29463251
TI  - Kidney autotransplantation after nephrectomy and work bench surgery as an
      ultimate approach to nephron-sparing surgery.
AB  - BACKGROUND: Kidney autotransplantation (KAT) is the ultimate approach for nephron
      sparing surgery. It is a rarely used method in renal tumor surgery today as
      minimal invasive and open techniques for nephron-sparing surgery improve
      constantly. In this publication, the complication rate and the long-term
      functional and oncological outcome at a single center are analyzed. METHODS: A
      prospectively constructed database of patients with renal tumors who underwent
      renal surgery was retrospectively analyzed to identify patients with KAT and
      describe surgical and oncological outcomes and to obtain long-term follow-up.
      Data collection included detailed surgical technique, complications (Clavian
      Dindo), and hospital stay, as well as functional and oncological outcome and long
      term follow-up. RESULTS: Between 1976 and 2013, 12 patients (median age 50.5
      years) underwent KAT for highly complex renal masses: in five cases for complex
      renal cell carcinoma (RCC), five cases for complex upper urinary tract carcinoma
      (UTUC), one case for a renal metastasis, and one case for nephroblastoma. The
      nephrectomy or nephron-ureterectomy was performed open via a flank or
      transabdominal. The median surgical time was 360 min (range 270-490 min).
      Intraoperatively, six cases required blood transfusions (50%). Six patients (50%)
      developed significant postoperative complications (Clavian-Dindo > 2). In two
      patients, intermittent hemodialysis for delayed graft function (16.6%) was
      needed, and in six cases (50%), additional blood transfusions postoperatively
      were necessary. At discharge from hospital, all patients had functioning grafts.
      The median hospital stay was 29.5 days (range 18-35). At follow-up (median follow
      up of 83.5 +/- 40.7 months), six patients had died (50%)-all with functioning
      grafts (free from hemodialysis). In five cases, recurrence of primary tumor or
      metastatic disease was recorded. In four cases, the recurrent carcinoma could be
      resected; in detail, UTUC in three cases and one partial nephrectomy of the
      autotransplanted kidney was performed. One patient suffered from bone and lung
      metastasis. Two patients died finally tumor-related. Five patients (41.6%) are
      presently alive, without evidence of tumor relapse. One patient developed
      terminal renal failure requiring hemodialysis 105 months after
      autotransplantation. One additional patient was lost to follow-up; after 69
      months, this patient had a functioning kidney and no evidence of disease
      recurrence at the last follow-up. A cumulative number of 1424 months without
      hemodialysis was gained for these 12 patients. In the literature to date, most
      KAT are performed in benign disease, with minor but frequent complication. Here,
      we report the largest series of KAT for malignant kidney tumors. The complication
      rates are similar, compared to the recently reported series for benign
      indications with an improved graft survival rate. Since KAT requires a complex
      and challenging surgical approach, it should be performed by experienced kidney
      transplant surgeons. CONCLUSION: In very complex cases involving renal tumors and
      multi-morbidity, patients should be counseled well before KAT is considered. At
      the same time, KAT should not be abandoned in these very rare cases, especially
      when a nephron-sparing approach is otherwise not feasible. KAT can maintain renal
      function and quality of life and extend expectancy of life.

PMID- 29463250
TI  - Grey matter volume in healthy and epileptic beagles using voxel-based morphometry
      - a pilot study.
AB  - BACKGROUND: One of the most common chronic neurological disorders in dogs is
      idiopathic epilepsy (IE) diagnosed as epilepsy without structural changes in the
      brain. In the current study the hypothesis should be proven that subtle grey
      matter changes occur in epileptic dogs. Therefore, magnetic resonance (MR) images
      of one dog breed (Beagles) were used to obtain an approximately uniform brain
      shape. Local differences in grey matter volume (GMV) were compared between 5
      healthy Beagles and 10 Beagles with spontaneously recurrent seizures (5 dogs with
      IE and 5 dogs with structural epilepsy (SE)), using voxel-based morphometry
      (VBM). T1W images of all dogs were prepared using Amira 6.3.0 for brain
      extraction, FSL 4.1.8 for registration and SPM12 for realignment. After creation
      of tissue probability maps of cerebrospinal fluid, grey and white matter from
      control images to segment all extracted brains, GM templates for each group were
      constructed to normalize brain images for parametric statistical analysis, which
      was achieved using SPM12. RESULTS: Epileptic Beagles (IE and SE Beagles)
      displayed statistically significant reduced GMV in olfactory bulb, cingulate
      gyrus, hippocampus and cortex, especially in temporal and occipital lobes.
      Beagles with IE showed statistically significant decreased GMV in olfactory bulb,
      cortex of parietal and temporal lobe, hippocampus and cingulate gyrus, Beagles
      with SE mild statistically significant GMV reduction in temporal lobe (p < 0.05;
      family- wise error correction). CONCLUSION: These results suggest that, as
      reported in epileptic humans, focal reduction in GMV also occurs in epileptic
      dogs. Furthermore, the current study shows that VBM analysis represents an
      excellent method to detect GMV differences of the brain between a healthy dog
      group and dogs with epileptic syndrome, when MR images of one breed are used.

PMID- 29463252
TI  - Anti-methicillin-resistance Staphylococcus aureus (MRSA) compounds from Bauhinia
      kockiana Korth. And their mechanism of antibacterial activity.
AB  - BACKGROUND: Bauhinia kockiana originates from Peninsular Malaysia and it is grown
      as a garden ornamental plant. Our previous study reported that this plant
      exhibited fairly strong antioxidant and antimicrobial activities. This paper
      focused on the assessment of the antibacterial activity of B. kockiana towards
      methicillin-resistance Staphylococcus aureus (MRSA), to purify and to identify
      the antibacterial compounds, and to determine the mechanism of antibacterial
      activity. METHODS: Antibacterial activity of B. kockiana flower was evaluated
      qualitatively and quantitatively using disc diffusion assay and microbroth
      dilution method. Minimum inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC) of extracts were examined. Phytochemical analysis was
      performed to determine the classes of phytochemicals in the extracts. Bioactivity
      guided isolation was employed to purify the antibacterial agents and identified
      via various spectroscopy methods. Scanning electron microscopy (SEM) technique
      was used to evaluate the antibacterial mechanism of extract and compounds
      isolated. RESULTS: B. kockiana flower was found to exhibit fairly strong
      antibacterial activity towards both strains of MRSA bacteria used, MIC varies
      from 62.5-250 MUg/mL. Tannins and flavonoids have been detected in the
      phytochemical analysis. Gallic acid and its ester derivatives purified from ethyl
      acetate extract could inhibit MRSA at 250-500 MUg/mL. SEM revealed that the cells
      have undergone plasmolysis upon treatment with the extract and compounds.
      CONCLUSION: Tannins and polyphenols are the antibacterial components towards MRSA
      in B. kockiana. Massive leakage of the cell content observed in treated cells
      showed that the phytochemicals have changed the properties of the cell membranes.
      Amphiphilic nature of the compounds exhibited the antibacterial activity towards
      MRSA via three stages: (1) cell membrane attachment; (2) cell membrane fluidity
      modification; and (3) cell membrane structure disruption.

PMID- 29463253
TI  - Evaluation of health resource utilization efficiency in community health centers
      of Jiangsu Province, China.
AB  - BACKGROUND: While the demand for health services keep escalating at the grass
      roots or rural areas of China, a substantial portion of healthcare resources
      remain stagnant in the more developed cities and this has entrenched health
      inequity in many parts of China. At its conception, China's Deepen Medical Reform
      started in 2012 was intended to flush out possible disparities and promote a more
      equitable and efficient distribution of healthcare resources. Nearly half a
      decade of this reform, there are uncertainties as to whether the attainment of
      the objectives of the reform is in sight. METHODS: Using a hybrid of panel data
      analysis and an augmented data envelopment analysis (DEA), we model human
      resources, material, finance to determine their technical and scale efficiency to
      comprehensively evaluate the transverse and longitudinal allocation efficiency of
      community health resources in Jiangsu Province. RESULTS: We observed that the
      Deepen Medical Reform in China has led to an increase concern to ensure efficient
      allocation of community health resources by health policy makers in the province.
      This has led to greater efficiency in health resource allocation in Jiangsu in
      general but serious regional or municipal disparities still exist. Using the DEA
      model, we note that the output from the Community Health Centers does not
      commensurate with the substantial resources (human resources, materials, and
      financial) invested in them. We further observe that the case is worst in less
      developed Northern parts of Jiangsu Province. CONCLUSIONS: The government of
      Jiangsu Province could improve the efficiency of health resource allocation by
      improving the community health service system, rationalizing the allocation of
      health personnel, optimizing the allocation of material resources, and enhancing
      the level of health of financial resource allocation.

PMID- 29463255
TI  - Oncological, surgical and functional results of the treatment of patients after
      hemipelvectomy due to metastases.

PMID- 29463254
TI  - Spinacia oleracea extract attenuates disease progression and sub-chondral bone
      changes in monosodium iodoacetate-induced osteoarthritis in rats.
AB  - BACKGROUND: Spinacia oleracea is an important dietary vegetable in India and
      throughout the world and has many beneficial effects. It is cultivated globally.
      However, its effect on osteoarthritis that mainly targets the cartilage cells
      remains unknown. In this study we aimed to evaluate the anti-osteoarthritic and
      chondro-protective effects of SOE on chemically induced osteoarthritis (OA).
      METHODS: OA was induced by intra-patellar injection of monosodium iodoacetate
      (MIA) at the knee joint in rats. SOE was then given orally at 250 and 500 mg.kg-
      1 day- 1 doses for 28 days to these rats. Anti-osteoarthritic potential of SOE
      was evaluated by micro-CT, mRNA and protein expression of pro-inflammatory and
      chondrogenic genes, clinically relevant biomarker's and behavioural experiments.
      RESULTS: In vitro cell free and cell based assays indicated that SOE acts as a
      strong anti-oxidant and an anti-inflammatory agent. Histological analysis of knee
      joints at the end of the experiment by safranin-o and toluidine blue staining
      established its protective effect. Radiological data corroborated the findings
      with improvement in the joint space and irregularity of the articular and
      atrophied femoral condyles and tibial plateau. Micro-CT analysis of sub-chondral
      bone indicated that SOE had the ability to mitigate OA effects by increasing bone
      volume to tissue volume (BV/TV) which resulted in decrease of trabecular pattern
      factor (Tb.Pf) by more than 200%. SOE stimulated chondrogenic marker gene
      expression with reduction in pro-inflammatory markers. Purified compounds
      isolated from SOE exhibited increased Sox-9 and Col-II protein expression in
      articular chondrocytes. Serum and urine analysis indicated that SOE had the
      potential to down-regulate glutathione S-transferase (GST) activity, clinical
      markers of osteoarthritis like cartilage oligometric matrix protein (COMP) and
      CTX-II. Overall, this led to a significant improvement in locomotion and
      balancing activity in rats as assessed by Open-field and Rota rod test.
      CONCLUSION: On the basis of in vitro and in vivo experiments performed with
      Spinacea oleracea extract we can deduce that SOE has the ability to alleviate the
      MIA induced deleterious effects.

PMID- 29463256
TI  - Developing the National Knowledge Platform in India: a policy and institutional
      analysis.
AB  - BACKGROUND: The importance of strong engagement between researchers and decision
      makers in the improvement of health systems is increasingly being recognised in
      low- and middle-income countries (LMICs). In 2013, in India, the Ministry of
      Health and Family Welfare began exploring the formation of a National Knowledge
      Platform (NKP) for guiding and supporting public health and health systems
      research in the country. The development of the NKP represents an important
      opportunity to enhance the linkage between policy-makers and researchers from the
      health policy and systems research field in India. However, the development
      process also reflects the highly complex reality of policy-making in the Indian
      health sector. Our objective is to provide insight into the policy-making process
      for establishing a health sector knowledge platform in India, and in doing so, to
      analyse the enabling contextual factors, the interests and actions of
      stakeholders, and the varying institutional arrangements explored in the
      development of the NKP. METHODS: We used a qualitative case study methodology,
      conducting 16 in-depth interviews and reviewing 42 documents. We utilised General
      Thematic Analysis to analyse our data. Our research team combined perspectives
      from both outsiders (independent researchers with no prior or current involvement
      with the policy) and insiders (researchers involved in the policy-making
      process). RESULTS: We found that enabling contextual factors, and a combination
      of government and non-governmental stakeholders with core interests in public
      health and health systems, were able to gain considerable momentum in moving the
      idea for the NKP forward. However, complex evidence-to-policy processes in the
      Indian health sector resulted in complications in determining the right
      institutional arrangement for the platform. Establishing the appropriate balance
      between legitimacy and independence, as well as frequent changes in institutional
      leadership, were found to be additional issues that stakeholders contended with
      in building the NKP. CONCLUSION: As interest in platforms linking health sector
      policy-makers and researchers grows in LMICs, our findings may allow stakeholders
      to learn from the Indian experience thus far, and to anticipate some of the
      facilitators and barriers that could potentially arise in establishing such
      mechanisms.

PMID- 29463257
TI  - Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression
      in alveolar epithelial cells type II.
AB  - BACKGROUND: Understanding the molecular mechanisms of nanomaterial interacting
      with cellular systems is important for appropriate risk assessment. The
      identification of early biomarkers for potential (sub-)chronic effects of
      nanoparticles provides a promising approach towards cost-intensive and animal
      consuming long-term studies. As part of a 90-day inhalation toxicity study with
      CeO2 NM-212 and BaSO4 NM-220 the present investigations on gene expression and
      immunohistochemistry should reveal details on underlying mechanisms of pulmonary
      effects. The role of alveolar epithelial cells type II (AEII cells) is focused
      since its contribution to defense against inhaled particles and potentially
      resulting adverse effects is assumed. Low dose levels should help to specify
      particle-related events, including inflammation and oxidative stress. RESULTS:
      Rats were exposed to clean air, 0.1, 0.3, 1.0, and 3.0 mg/m3 CeO2 NM-212 or 50.0
      mg/m3 BaSO4 NM-220 and the expression of 391 genes was analyzed in AEII cells
      after one, 28 and 90 days exposure. A total number of 34 genes was regulated,
      most of them related to inflammatory mediators. Marked changes in gene expression
      were measured for Ccl2, Ccl7, Ccl17, Ccl22, Ccl3, Ccl4, Il-1alpha, Il-1beta, and
      Il-1rn (inflammation), Lpo and Noxo1 (oxidative stress), and Mmp12
      (inflammation/lung cancer). Genes related to genotoxicity and apoptosis did not
      display marked regulation. Although gene expression was less affected by BaSO4
      compared to CeO2 the gene pattern showed great overlap. Gene expression was
      further analyzed in liver and kidney tissue showing inflammatory responses in
      both organs and marked downregulation of oxidative stress related genes in the
      kidney. Increases in the amount of Ce were measured in liver but not in kidney
      tissue. Investigation of selected genes on protein level revealed increased Ccl2
      in bronchoalveolar lavage of exposed animals and increased Lpo and Mmp12 in the
      alveolar epithelia. CONCLUSION: AEII cells contribute to CeO2 nanoparticle caused
      inflammatory and oxidative stress reactions in the respiratory tract by the
      release of related mediators. Effects of BaSO4 exposure are low. However, overlap
      between both substances were detected and support identification of potential
      early biomarkers for nanoparticle effects on the respiratory system. Signs for
      long-term effects need to be further evaluated by comparison to a respective
      exposure setting.

PMID- 29463259
TI  - Climatic fluctuations and malaria transmission dynamics, prior to elimination, in
      Guna Yala, Republica de Panama.
AB  - BACKGROUND: Malaria has historically been entrenched in indigenous populations of
      the Republica de Panama. This scenario occurs despite the fact that successful
      methods for malaria elimination were developed during the creation of the Panama
      Canal. Today, most malaria cases in the Republica de Panama affect the Gunas, an
      indigenous group, which mainly live in autonomous regions of eastern Panama. Over
      recent decades several malaria outbreaks have affected the Gunas, and one
      hypothesis is that such outbreaks could have been exacerbated by climate change,
      especially by anomalous weather patterns driven by the EL Nino Southern
      Oscillation (ENSO). RESULTS: Monthly malaria cases in Guna Yala (1998-2016) were
      autocorrelated up to 2 months of lag, likely reflecting parasite transmission
      cycles between humans and mosquitoes, and cyclically for periods of 4 months that
      might reflect relapses of Plasmodium vivax, the dominant malaria parasite
      transmitted in Panama. Moreover, malaria case number was positively associated (P
      < 0.05) with rainfall (7 months of lag), and negatively with the El Nino 4 index
      (15 months of lag) and the Normalized Difference Vegetation Index, NDVI (8 months
      of lag), the sign and magnitude of these associations likely related to the
      impacts of weather patterns and vegetation on the ecology of Anopheles albimanus,
      the main malaria vector in Guna Yala. Interannual cycles, of approximately 4-year
      periods, in monthly malaria case numbers were associated with the El Nino 4
      index, a climatic index associated with weather and vegetation dynamics in Guna
      Yala at seasonal and interannual time scales. CONCLUSION: The results showed that
      ENSO, rainfall and NDVI were associated with the number of malaria cases in Guna
      Yala during the study period. These results highlight the vulnerability of Guna
      populations to malaria, an infection sensitive to climate change, and call for
      further studies about weather impacts on malaria vector ecology, as well as the
      association of malaria vectors with Gunas paying attention to their socio
      economic conditions of poverty and cultural differences as an ethnic minority.

PMID- 29463258
TI  - The association between subgroups of MRI findings identified with latent class
      analysis and low back pain in 40-year-old Danes.
AB  - BACKGROUND: Research into the clinical importance of spinal MRI findings in
      patients with low back pain (LBP) has primarily focused on single imaging
      findings, such as Modic changes or disc degeneration, and found only weak
      associations with the presence of pain. However, numerous MRI findings almost
      always co-exist in the lumbar spine and are often present at more than one lumbar
      level. It is possible that multiple MRI findings are more strongly associated
      with LBP than single MRI findings. Latent Class Analysis is a statistical method
      that has recently been tested and found useful for identifying latent classes
      (subgroups) of MRI findings within multivariable datasets. The purpose of this
      study was to investigate the association between subgroups of MRI findings and
      the presence of LBP in people from the general population. METHODS: To identify
      subgroups of lumbar MRI findings with potential clinical relevance, Latent Class
      Analysis was initially performed on a clinical dataset of 631 patients seeking
      care for LBP. Subsequently, 412 participants in a general population cohort (the
      'Backs on Funen' project) were statistically allocated to those existing
      subgroups by Latent Class Analysis, matching their MRI findings at a segmental
      level. The subgroups containing MRI findings from the general population were
      then organised into hypothetical pathways of degeneration and the association
      between subgroups in the pathways and the presence of LBP was tested using exact
      logistic regression. RESULTS: Six subgroups were identified in the clinical
      dataset and the data from the general population cohort fitted the subgroups
      well, with a median posterior probability of 93%-100%. These six subgroups
      described two pathways of increasing degeneration on upper (L1-L3) and lower (L4
      L5) lumbar levels. An association with LBP was found for the subgroups describing
      severe and multiple degenerative MRI findings at the lower lumbar levels but none
      of the other subgroups were associated with LBP. CONCLUSION: Although MRI
      findings are common in asymptomatic people and the association between single MRI
      findings and LBP is often weak, our results suggest that subgroups of multiple
      and severe lumbar MRI findings have a stronger association with LBP than those
      with milder degrees of degeneration.

PMID- 29463260
TI  - Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+
      breast cancer.
AB  - BACKGROUND: Tamoxifen is the standard endocrine therapy for breast cancers, which
      require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower
      and variable concentrations of CYP activity at the tumor remain major bottlenecks
      for the efficient treatment, causing severe side-effects. Combination nanotherapy
      has gained much recent attention for cancer treatment as it reduces the drug
      associated toxicity without affecting the therapeutic response. RESULTS: Here we
      show the modular design of P22 bacteriophage virus-like particles for nanoscale
      integration of virus-driven enzyme prodrug therapy and photodynamic therapy.
      These virus capsids carrying CYP activity at the core are decorated with
      photosensitizer and targeting moiety at the surface for effective combinatory
      treatment. The estradiol-functionalized nanoparticles are recognized and
      internalized into ER+ breast tumor cells increasing the intracellular CYP
      activity and showing the ability to produce reactive oxygen species (ROS) upon
      UV365 nm irradiation. The generated ROS in synergy with enzymatic activity
      drastically enhanced the tamoxifen sensitivity in vitro, strongly inhibiting
      tumor cells. CONCLUSIONS: This work clearly demonstrated that the targeted
      combinatory treatment using multifunctional biocatalytic P22 represents the
      effective nanotherapeutics for ER+ breast cancer.

PMID- 29463261
TI  - HMGB2 is associated with malignancy and regulates Warburg effect by targeting
      LDHB and FBP1 in breast cancer.
AB  - BACKGROUND: High-mobility group box 2 (HMGB2) is implicated in tumorigenesis in
      various cancers. However, the clinical significance of HMGB2 signaling in human
      breast cancer progression remains unknown. METHODS: We investigated HMGB2
      expression in 185 cases of primary breast cancer and matched normal breast tissue
      specimens, and explored the underlying mechanisms of altered HMGB2 expression as
      well as the impact of this altered expression on breast cancer growth and on
      aerobic glycolysis using in vitro and animal models of breast cancer. RESULTS:
      HMGB2 was more highly expressed in tumor-cell nuclei of breast cancer cells than
      in the adjacent normal breast tissues (P < 0.05). Higher HMGB2 expression
      correlated with larger tumor size (P = 0.003) and advanced tumor stage (P =
      0.033). A Cox proportional hazards model revealed that HMGB2 expression was an
      independent prognostic factor for breast cancer after radical resection (P <
      0.05). Experimentally, knockdown of HMGB2 expression by stable transfected shRNA
      significantly decreased the growth and glycolysis of breast cancer cells both in
      vitro and in mouse models. Mechanically, promotion of breast cancer progression
      by HMGB2 directly and significantly correlated with activation of LDHB expression
      and inactivation of FBP1 expression. CONCLUSIONS: These results disclose a novel
      role for HMGB2 in reprogramming the metabolic process in breast cancer cells by
      targeting LDHB and FBP1 and provide potential prognostic predictors for breast
      cancer patients.

PMID- 29463263
TI  - Correction to: World-wide research architecture of vitamin D research: density
      equalizing mapping studies and socio-economic analysis.
AB  - After publication of the original article [1], the authors reported two errors
      which needed to be corrected.

PMID- 29463262
TI  - Potential role of insulin receptor isoforms and IGF receptors in plaque
      instability of human and experimental atherosclerosis.
AB  - BACKGROUND: Clinical complications associated with atherosclerotic plaques arise
      from luminal obstruction due to plaque growth or destabilization leading to
      rupture. We previously demonstrated that overexpression of insulin receptor
      isoform A (IRA) and insulin-like growth factor-I receptor (IGF-IR) confers a
      proliferative and migratory advantage to vascular smooth muscle cells (VSMCs)
      promoting plaque growth in early stages of atherosclerosis. However, the role of
      insulin receptor (IR) isoforms, IGF-IR or insulin-like growth factor-II receptor
      (IGF-IIR) in VSMCs apoptosis during advanced atherosclerosis remains unclear.
      METHODS: We evaluated IR isoforms expression in human carotid atherosclerotic
      plaques by consecutive immunoprecipitations of insulin receptor isoform B (IRB)
      and IRA. Western blot analysis was performed to measure IGF-IR, IGF-IIR, and
      alpha-smooth muscle actin (alpha-SMA) expression in human plaques. The expression
      of those proteins, as well as the presence of apoptotic cells, was analyzed by
      immunohistochemistry in experimental atherosclerosis using BATIRKO; ApoE-/- mice,
      a model showing more aggravated vascular damage than ApoE-/- mice. Finally,
      apoptosis of VSMCs bearing IR (IRLoxP+/+ VSMCs), or not (IR-/- VSMCs), expressing
      IRA (IRA VSMCs) or expressing IRB (IRB VSMCs), was assessed by Western blot
      against cleaved caspase 3. RESULTS: We observed a significant decrease of IRA/IRB
      ratio in human complicated plaques as compared to non-complicated regions.
      Moreover, complicated plaques showed a reduced IGF-IR expression, an increased
      IGF-IIR expression, and lower levels of alpha-SMA indicating a loss of VSMCs. In
      experimental atherosclerosis, we found a significant decrease of IRA with an
      increased IRB expression in aorta from 24-week-old BATIRKO; ApoE-/- mice.
      Furthermore, atherosclerotic plaques from BATIRKO; ApoE-/- mice had less VSMCs
      content and higher number of apoptotic cells. In vitro experiments showed that
      IGF-IR inhibition by picropodophyllin induced apoptosis in VSMCs. Apoptosis
      induced by thapsigargin was lower in IR-/- VSMCs expressing higher IGF-IR levels
      as compared to IRLoxP+/+ VSMCs. Finally, IRB VSMCs are more prone to thapsigargin
      induced apoptosis than IRA or IRLoxP+/+ VSMCs. CONCLUSIONS: In advanced human
      atherosclerosis, a reduction of IRA/IRB ratio, decreased IGF-IR expression, or
      increased IGF-IIR may contribute to VSMCs apoptosis, promoting plaque instability
      and increasing the risk of plaque rupture and its clinical consequences.

PMID- 29463264
TI  - Using non-exceedance probabilities of policy-relevant malaria prevalence
      thresholds to identify areas of low transmission in Somalia.
AB  - BACKGROUND: Countries planning malaria elimination must adapt from sustaining
      universal control to targeted intervention and surveillance. Decisions to make
      this transition require interpretable information, including malaria parasite
      survey data. As transmission declines, observed parasite prevalence becomes
      highly heterogeneous with most communities reporting estimates close to zero.
      Absolute estimates of prevalence become hard to interpret as a measure of
      transmission intensity and suitable statistical methods are required to handle
      uncertainty of area-wide predictions that are programmatically relevant. METHODS:
      A spatio-temporal geostatistical binomial model for Plasmodium falciparum
      prevalence (PfPR) was developed using data from cross-sectional surveys conducted
      in Somalia in 2005, 2007-2011 and 2014. The fitted model was then used to
      generate maps of non-exceedance probabilities, i.e. the predictive probability
      that the region-wide population-weighted average PfPR for children between 2 and
      10 years (PfPR2-10) lies below 1 and 5%. A comparison was carried out with the
      decision-making outcomes from those of standard approaches that ignore
      uncertainty in prevalence estimates. RESULTS: By 2010, most regions in Somalia
      were at least 70% likely to be below 5% PfPR2-10 and, by 2014, 17 regions were
      below 5% PfPR2-10 with a probability greater than 90%. Larger uncertainty is
      observed using a threshold of 1%. By 2011, only two regions were more than 90%
      likely of being < 1% PfPR2-10 and, by 2014, only three regions showed such low
      level of uncertainty. The use of non-exceedance probabilities indicated that
      there was weak evidence to classify 10 out of the 18 regions as < 1% in 2014,
      when a greater than 90% non-exceedance probability was required. CONCLUSION:
      Unlike standard approaches, non-exceedance probabilities of spatially modelled
      PfPR2-10 allow to quantify uncertainty of prevalence estimates in relation to
      policy relevant intervention thresholds, providing programmatically relevant
      metrics to make decisions on transitioning from sustained malaria control to
      strategies that encompass methods of malaria elimination.

PMID- 29463265
TI  - Fatty acids modulate the expression levels of key proteins for cholesterol
      absorption in Caco-2 monolayer.
AB  - BACKGROUND: Fatty acids have been shown to modulate intestinal cholesterol
      absorption in cells and animals, a process that is mediated by several
      transporter proteins. Of these proteins, Niemann-Pick C1-Like 1 (NPC1L1) is a
      major contributor to this process. The current study investigates the unknown
      mechanism by which fatty acids modulate cholesterol absorption. METHODS: We
      evaluated the effects of six fatty acids palmitic acid (PAM), oleic acid (OLA),
      linoleic acid (LNA), arachidonic acid (ARA), eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) on cholesterol uptake and transport in human
      enterocytes Caco-2 cells, and on the mRNA expression levels of NPC1L1, others
      proteins (ABCG5, ABCG8, ABCA1, ACAT2, MTP, Caveolin 1, Annexin-2) involved in
      cholesterol absorption, and SREBP-1 and SREBP-2 that are responsible for lipid
      metabolism. RESULTS: The polyunsaturated fatty acids (PUFAs), especially for EPA
      and DHA, dose-dependently inhibited cholesterol uptake and transport in Caco-2
      monolayer, while saturated fatty acids (SFAs) and monounsaturated fatty acids
      (MUFAs) had no inhibitory effects. EPA and DHA inhibited cholesterol absorption
      in Caco-2 monolayer might be caused by down-regulating NPC1L1 mRNA and protein
      levels, which were associated with inhibition of SREBP-1/- 2 mRNA expression
      levels. CONCLUSION: Results from this study indicate that functional food
      containing high PUFAs may have potential therapeutic benefit to reduce
      cholesterol absorption. Further studies on this topic may provide approaches to
      control lipid metabolism and to promote health.

PMID- 29463266
TI  - Unresectable hepatic PEComa: a rare malignancy treated with stereotactic body
      radiation therapy (SBRT) followed by complete resection.
AB  - BACKGROUND: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal
      tumors occurring in various anatomic regions. Although diagnostic criteria and
      treatment management are not established, current treatment options consist of
      surgery and chemotherapy including mTOR inhibitors. Stereotactic body radiation
      therapy (SBRT) is a non-invasive ablative treatment which has shown excellent
      control rates for more common types of unresectable liver tumors and metastases.
      In this report we present a rare case of PEComa of the liver that was treated by
      stereotactic radiotherapy followed by resection. Staging and evaluation of
      treatment response was done by FDG-PET/CT. This case highlights the potential of
      SBRT as a neoadjuvant treatment even for rare liver malignancies. It is the first
      case of liver PEComa treated by SBRT and resection. CASE PRESENTATION: A 52-year
      old woman presented at an external hospital with abdominal pressure and pain in
      the right upper abdominal quadrant. A CT scan showed a 700 cm3 liver lesion in
      segment IV. In repeated biopsy in July 2015 histopathological workup showed a
      pleomorphic epitheloid tumor with small to medium sized cells expressing vimentin
      and melan-A while being negative for cytokeratin establishing the diagnosis of
      PEComa of the liver. To achieve high, ablative doses a stereotactic body
      radiotherapy (SBRT) technique was chosen consisting of 60Gy (biologically
      effective dose 105Gy) in 8 fractions of 7.5Gy. Radiotherapy planning was based on
      MRI resulting in a planning target volume (PTV) of 1944 cm3. Treatment toxicity
      was limited to a slight elevation of transaminases (grade 1 and 3). A complete
      resection was performed 21 weeks after radiotherapy confirmed by negative
      surgical margins. At last follow-up 21 months after therapy, MRI showed neither
      local nor distant tumor recurrence. The patient was in stable condition (ECOG 1)
      and without late radiation toxicity. CONCLUSIONS: This is the first documented
      case of liver PEComa treated by SBRT and resection. A favorable post-treatment
      course demonstrates that SBRT is a potential neoadjuvant treatment that is
      capable of reducing an inoperable rare liver tumor to a resectable lesion.

PMID- 29463267
TI  - Hippocampus-sparing radiotherapy using volumetric modulated arc therapy (VMAT) to
      the primary brain tumor: the result of dosimetric study and neurocognitive
      function assessment.
AB  - BACKGROUND: We hypothesized that hippocampal-sparing radiotherapy via volumetric
      modulated arc therapy (VMAT) could preserve the neurocognitive function (NCF) of
      patients with primary brain tumors treated with radiotherapy. METHODS: We
      reviewed data from patients with primary brain tumors who underwent hippocampal
      sparing brain radiotherapy via VMAT between February 2014 and December 2015. The
      optimization criteria for the contralateral hippocampus was a maximum dose (Dmax)
      of less than 17 Gy. For NCF evaluations, the Seoul Verbal Learning Test for total
      recall, delayed recall, and recognition (SVLT-TR, DR, and Recognition) was
      performed at baseline and at seven months after radiotherapy. RESULTS: A total of
      26 patients underwent NCF testing seven months after radiotherapy. Their median
      age was 49.5 years (range 26-77 years), and 14 (53.8%) had grade III/IV tumors.
      The median Dmax to the contralateral hippocampus was 16.4 Gy (range 3.5-63.4).
      The median mean dose to the contralateral hippocampus, expressed as equivalent to
      a 2-Gy dose (EQD2/2), was 7.4 Gy2 (0.7-13.1). The mean relative changes in SVLT
      TR, SVLT-DR, and SVLT-Recognition at seven months compared to the baseline were -
      7.7% (95% confidence interval [CI], - 19.6% to 4.2%), - 9.2% (95% CI, - 25.4% to
      7.0%), and - 3.4% (- 12.7% to 5.8%), respectively. Two patients (7.7%) showed
      deteriorated NCF in the SVLT-TR and SVLT-DR, and three (11.5%) in the SVLT
      Recognition. The mean dose of the left hippocampus and bilateral hippocampi were
      significantly higher in patients showing deterioration of the SVLT-TR and SVLT
      Recognition than in those without deterioration. CONCLUSIONS: The contralateral
      hippocampus could be effectively spared in patients with primary brain tumor via
      VMAT to preserve the verbal memory function. Further investigation is needed to
      identify those patients who will most benefit from hippocampal-sparing
      radiotherapy of the primary brain tumor.

PMID- 29463268
TI  - Influence of coronary territory on flow profiles of saphenous vein grafts.
AB  - BACKGROUND: Differing perfusion of the left and right ventricular coronary
      territory may influence flow-profiles of saphenous vein grafts (SVGs). We
      compared flow parameters, measured by transit-time flowmetry (TTFM), in left- and
      right-sided SVGs during coronary artery by-pass grafting (CABG). METHODS: Routine
      TTFM measurements were obtained in 167 SVGs to the left territory (55%) and 134
      SVGs to the right territory (total of 301 SVGs in 207 patients). The four
      standard TTFM parameters, [mean graft flow (MGF), pulsatility index (PI),
      percentage diastolic filling (%DF), and percentage backward flow (%BF)] were
      compared. Differences in flow parameters were also examined according to surgical
      technique (on- vs. off-pump). RESULTS: No significant difference between coronary
      territories was found for MGF, PI and %BF. However, a higher %DF was noted in
      left-sided SVGs in the overall cohort as well as in the on-pump (both p < 0.001)
      and the off-pump cohorts (p = 0.07). Further, a significantly higher %BF was
      found in SVGs performed off-pump to the left territory (1.2 +/- 2.5 vs. 2.3 +/-
      3.0, p = 0.023). In a multivariate regression analysis, anastomosing a SVG to the
      left territory was weakly associated with higher PI (OR = 0.36, p = 0.026) and
      strongly associated with higher %DF (OR = 5.1, p < 0.001). No significant
      association was found for MGF, PI, %DF or %BF in either the on-pump nor the off
      pump cohorts. CONCLUSIONS: Although statistically significant, the established
      differences in TTFM parameters between left- and right-sided vein grafts were
      small and unlikely to be of clinical relevance.

PMID- 29463269
TI  - Telomere attrition in heart failure: a flow-FISH longitudinal analysis of
      circulating monocytes.
AB  - BACKGROUND: Cross-sectional investigations report shorter telomeres in patients
      with heart failure (HF); however, no studies describe telomere length (TL)
      trajectory and its relationship with HF progression. Here we aimed to investigate
      telomere shortening over time and its relationship to outcomes. METHODS: Our
      study cohort included 101 ambulatory patients with HF. Blood samples were
      collected at baseline (n = 101) and at the 1-year follow-up (n = 54). Using flow
      FISH analysis of circulating monocytes, we simultaneously measured three monocyte
      subsets-classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical
      (CD14+CD16++)-and their respective TLs based on FITC-labeled PNA probe
      hybridization. The primary endpoints were all-cause death and the composite of
      all-cause death or HF-related hospitalization, assessed at 2.3 +/- 0.6 years. All
      statistical analyses were executed by using the SPSS 15.0 software, and included
      Student's t test and ANOVA with post hoc Scheffe analysis, Pearson or Spearman
      rho correlation and univariate Cox regression when applicable. RESULTS: We found
      high correlations between TL values of different monocyte subsets: CD14++CD16+
      vs. CD14++CD16-, R = 0.95, p < 0.001; CD14++CD16+ vs. CD14+CD16++, R = 0.90, p <
      0.001; and CD14++CD16- vs. CD14+CD16++, R = 0.89, p < 0.001. Mean monocyte TL
      exhibited significant attrition from baseline to the 1-year follow-up (11.1 +/-
      3.3 vs. 8.3 +/- 2.1, p < 0.001). TL did not significantly differ between monocyte
      subsets at either sampling time-point (all p values > 0.1). Cox regression
      analyses did not indicate that TL or DeltaTL was associated with all-cause death
      or the composite endpoint. CONCLUSIONS: Overall, this longitudinal study
      demonstrated a ~ 22% reduction of TL in monocytes from ambulatory patients with
      HF within 1 year. TL and DeltaTL were not related to outcomes over long-term
      follow-up.

PMID- 29463270
TI  - The unfunded priorities: an evaluation of priority setting for noncommunicable
      disease control in Uganda.
AB  - BACKGROUND: The double burden of infectious diseases coupled with noncommunicable
      diseases poses unique challenges for priority setting and for achieving equitable
      action to address the major causes of disease burden in health systems already
      impacted by limited resources. Noncommunicable disease control is an important
      global health and development priority. However, there are challenges for
      translating this global priority into local priorities and action. The aim of
      this study was to evaluate the influence of national, sub-national and global
      factors on priority setting for noncommunicable disease control in Uganda and
      examine the extent to which priority setting was successful. METHODS: A mixed
      methods design that used the Kapiriri & Martin framework for evaluating priority
      setting in low income countries. The evaluation period was 2005-2015. Data
      collection included a document review (policy documents (n = 19); meeting minutes
      (n = 28)), media analysis (n = 114) and stakeholder interviews (n = 9). Data were
      analysed according to the Kapiriri & Martin (2010) framework. RESULTS: Priority
      setting for noncommunicable diseases was not entirely fair nor successful. While
      there were explicit processes that incorporated relevant criteria, evidence and
      wide stakeholder involvement, these criteria were not used systematically or
      consistently in the contemplation of noncommunicable diseases. There were
      insufficient resources for noncommunicable diseases, despite being a priority
      area. There were weaknesses in the priority setting institutions, and
      insufficient mechanisms to ensure accountability for decision-making. Priority
      setting was influenced by the priorities of major stakeholders (i.e. development
      assistance partners) which were not always aligned with national priorities.
      There were major delays in the implementation of noncommunicable disease-related
      priorities and in many cases, a failure to implement. CONCLUSIONS: This
      evaluation revealed the challenges that low income countries are grappling with
      in prioritizing noncommunicable diseases in the context of a double disease
      burden with limited resources. Strengthening local capacity for priority setting
      would help to support the development of sustainable and implementable
      noncommunicable disease-related priorities. Global support (i.e. aid) to low
      income countries for noncommunicable diseases must also catch up to align with
      NCDs as a global health priority.

PMID- 29463271
TI  - A simulation study on estimating biomarker-treatment interaction effects in
      randomized trials with prognostic variables.
AB  - BACKGROUND: To individualize treatment decisions based on patient
      characteristics, identification of an interaction between a biomarker and
      treatment is necessary. Often such potential interactions are analysed using data
      from randomized clinical trials intended for comparison of two treatments. Tests
      of interactions are often lacking statistical power and we investigated if and
      how a consideration of further prognostic variables can improve power and
      decrease the bias of estimated biomarker-treatment interactions in randomized
      clinical trials with time-to-event outcomes. METHODS: A simulation study was
      performed to assess how prognostic factors affect the estimate of the biomarker
      treatment interaction for a time-to-event outcome, when different approaches,
      like ignoring other prognostic factors, including all available covariates or
      using variable selection strategies, are applied. Different scenarios regarding
      the proportion of censored observations, the correlation structure between the
      covariate of interest and further potential prognostic variables, and the
      strength of the interaction were considered. RESULTS: The simulation study
      revealed that in a regression model for estimating a biomarker-treatment
      interaction, the probability of detecting a biomarker-treatment interaction can
      be increased by including prognostic variables that are associated with the
      outcome, and that the interaction estimate is biased when relevant prognostic
      variables are not considered. However, the probability of a false-positive
      finding increases if too many potential predictors are included or if variable
      selection is performed inadequately. CONCLUSIONS: We recommend undertaking an
      adequate literature search before data analysis to derive information about
      potential prognostic variables and to gain power for detecting true interaction
      effects and pre-specifying analyses to avoid selective reporting and increased
      false-positive rates.

PMID- 29463272
TI  - Colonic perineurioma (benign fibroblastic polyp): case report and review of the
      literature.
AB  - BACKGROUND: Colorectal perineuriomas are uncommon benign mucosal-based
      proliferations of mesenchymal cells that express perineurial markers, often
      associated with colonic crypts displaying a serrated/hyperplastic architecture.
      The vast majority of cases arise distal to the splenic flexure and have been
      described as sessile polyps. Using molecular analysis, BRAF mutations have been
      demonstrated in the serrated crypt epithelium. We report a new case of
      perineurioma presenting as a pedunculated polyp in the transverse colon, with
      prominent hemosiderin deposits in the uninvolved lamina propria that separated
      the perineurial proliferation from the surface epithelium, a previously
      unreported histological finding. By using immunohistochemistry, we demonstrated
      the presence of BRAF V600E mutated protein in the serrated crypt epithelium. In
      addition, a review of the literature on colorectal perineurioma is provided. CASE
      PRESENTATION: A 5 mm pedunculated polyp was removed from the transverse colon of
      a 42 year old man who presented with epigastric pain, weight loss and rectal
      bleeding. A proliferation of uniform plump spindled cells expanded the lamina
      propria and separated serrated colonic crypts. The epithelial component closely
      resembled microvesicular hyperplastic polyp. Immunohistochemical stains for
      epithelial membrane antigen (EMA), glucose transporter 1 (GLUT1) and collagen IV
      were positive in the stromal proliferation. A mutation-specific monoclonal
      antibody directed against BRAF V600E showed positive cytoplasmic staining in the
      serrated crypt epithelium but not in the perineurial proliferation. Conspicuous
      hemosiderin deposition was seen in the inflamed lamina propria between the
      perineurial proliferation and the surface epithelium. CONCLUSION: Although the
      majority of colorectal perineuriomas occur in the sigmoid colon and rectum and
      are described as sessile polyps, colorectal perineurioma can present as a
      pedunculated polyp proximal to the splenic flexure as described in this case.
      Conspicuous hemosiderin deposition can be seen in the superficial lamina propria.
      BRAF mutations are limited to the serrated crypt epithelium.

PMID- 29463273
TI  - Outcomes of oblique lateral interbody fusion for degenerative lumbar disease in
      patients under or over 65 years of age.
AB  - BACKGROUND: Oblique lateral interbody fusion (OLIF) offers the solution to
      problems of anterior lumbar interbody fusion (ALIF) and lateral lumbar interbody
      fusion (LLIF). However, OLIF technique for degenerative spinal diseases of
      elderly patients has been rarely reported. The objective of this study was to
      determine the clinical and radiological results of OLIF technique for
      degenerative spinal diseases in patients under or over 65 years of age. METHODS:
      Sixty-three patients who underwent OLIF procedure were enrolled, including 29
      patients who were less than 65 years of age and 34 patients who were over 65
      years of age. Fusion rate, change of disc height and lumbar lordotic angle,
      Numeric Rating Scale (NRS), return to daily activity, patient's satisfaction rate
      (PSR), and Oswestry disability index (ODI) were used to assess clinical and
      functional outcomes. RESULTS: The mean NRS scores for back and leg pain
      decreased, respectively, from 4.6 and 5.9 to 2.3 and 1.8 in the group A (less
      than 65 years) and from 4.5 and 6.8 to 2.6 and 2.2 in the group B (over 65 years)
      at the final follow-up period. The mean ODI scores improved from 48.4 to 24.0% in
      the group A and from 46.5 to 25.2% in the group B at the final follow-up period.
      In both groups, the NRS and ODI scores significantly changed preoperatively to
      postoperatively (p <  0.001). However, statistical analysis yielded no
      significant difference in postoperative NRS/ODI scores between two groups. In
      both groups, the changes in the disc height, segmental lordosis, and fusion rate
      between the preoperative and postoperative periods were significant. The amount
      of change between preoperative and postoperative disc height, segmental lordosis,
      and whole lumbar lordosis demonstrated significant intergroup differences (p < 
      0.05). Overall perioperative complications occurred in 8 of 29 (27.6%) patients
      in the group A and in 10 of 34 (29.4%) patients in the group B. In both groups,
      the major complication incidence was 0 and 3%, respectively. CONCLUSION: Although
      there was the slightly high incidence of complication associated with high rate
      of co-morbidities in elderly patients, OLIF for degenerative lumbar diseases in
      elderly patients showed favorable clinical and radiological outcomes.

PMID- 29463274
TI  - Along with its favorable prognostic role, CLCA2 inhibits growth and metastasis of
      nasopharyngeal carcinoma cells via inhibition of FAK/ERK signaling.
AB  - BACKGROUND: CLCA2 was reported as a tumor suppressor and disregulated in breast
      cancer. However, its function in tumor growth and metastasis in NPC has rarely
      been reported. In this study, we investigated the functional and molecular
      mechanisms by which CLCA2 influences NPC. METHODS: CLCA2 expression in human NPC
      cell lines and tissues was examined via real-time PCR (RT-PCR), Western blot and
      IHC. The biological roles of CLCA2 in proliferative, migration and invasion of
      NPC cell lines was evaluated in 5-8F, S18, S26 and SUNE-1 cells. Cell viability,
      migration and invasion were assessed in vitro by MTS, colony formation and
      transwell assay, respectively. CLCA2 in growth and metastasis of NPC were
      evaluated in vivo through NPC xenograft tumor growth, lung metastatic mice model
      and popliteal lymph node (LN) metastasis model. RESULTS: Overexpression of CLCA2
      significantly decreased proliferation, migration and invasion of NPC cells. In
      contrast, knockdown of CLCA2 elicited the opposite effects. CLCA2 overexpression
      suppressed xenograft tumor growth and lung, popliteal lymph node (LN) metastasis
      in vivo. CLCA2 inhibited tumor metastasis through suppressing epithelial
      Mesenchymal transition (EMT) and in-activating FAK/ERK1/2 signaling pathway in
      NPC cells. Immunohistochemical staining of 143 NPC samples revealed that CLCA2
      expression was an independent, favorable prognostic factor for overall survival
      and distant metastasis-free survival of patients. In addition, inhibition of FAK
      and ERK1/2 reversed CLCA2 silencing-induced tumor cell migration. Furthermore,
      inhibitors against chloride channels suppressed NPC cellular migration which
      could have been enhanced by the presence of CLCA2. CONCLUSION: CLCA2 suppress NPC
      proliferation, migration, invasion and epithelial-mesenchymal transition through
      inhibiting FAK/ERK signaling.

PMID- 29463275
TI  - Leukocyte telomere length in paediatric critical illness: effect of early
      parenteral nutrition.
AB  - BACKGROUND: Children who have suffered from critical illnesses that required
      treatment in a paediatric intensive care unit (PICU) have long-term physical and
      neurodevelopmental impairments. The mechanisms underlying this legacy remain
      largely unknown. In patients suffering from chronic diseases hallmarked by
      inflammation and oxidative stress, poor long-term outcome has been associated
      with shorter telomeres. Shortened telomeres have also been reported to result
      from excessive food consumption and/or unhealthy nutrition. We investigated
      whether critically ill children admitted to the PICU have shorter-than-normal
      telomeres, and whether early parenteral nutrition (PN) independently affects
      telomere length when adjusting for known determinants of telomere length.
      METHODS: Telomere length was quantified in leukocyte DNA from 342 healthy
      children and from 1148 patients who had been enrolled in the multicenter,
      randomised controlled trial (RCT), PEPaNIC. These patients were randomly
      allocated to initiation of PN within 24 h (early PN) or to withholding PN for one
      week in PICU (late PN). The impact of early PN versus late PN on the change in
      telomere length from the first to last PICU-day was investigated with
      multivariable linear regression analyses. RESULTS: Leukocyte telomeres were 6%
      shorter than normal upon PICU admission (median 1.625 (IQR 1.446-1.825)
      telomere/single-copy-gene ratio (T/S) units vs. 1.727 (1.547-1.915) T/S-units in
      healthy children (P < 0.0001)). Adjusted for potential baseline determinants and
      leukocyte composition, early PN was associated with telomere shortening during
      PICU stay as compared with late PN (estimate early versus late PN -0.021 T/S
      units, 95% CI -0.038; 0.004, P = 0.01). Other independent determinants of
      telomere length identified in this model were age, gender, baseline telomere
      length and fraction of neutrophils in the sample from which the DNA was
      extracted. Telomere shortening with early PN was independent of post
      randomisation factors affected by early PN, including longer length of PICU stay,
      larger amounts of insulin and higher risk of infection. CONCLUSIONS: Shorter than
      normal leukocyte telomeres are present in critically ill children admitted to the
      PICU. Early initiation of PN further shortened telomeres, an effect that was
      independent of other determinants. Whether such telomere-shortening predisposes
      to long-term consequences of paediatric critical illness should be further
      investigated in a prospective follow-up study. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT01536275 . Registered on 16 February 2012.

PMID- 29463276
TI  - Correction to: Clinicopathological predictors of recurrence in nodular and
      superficial spreading cutaneous melanoma: a multivariate analysis of 214 cases.
AB  - In the original version of this article [1], published on 7 November 2017,
      affiliation 18 has been incorrectly assigned to the authors Serena Magi and Laura
      Mazzoni. They are only affiliated to the Skin Cancer Unit, Istituto Tumori
      Romagna (IRST), Meldola, Italy (affiliation 5).

PMID- 29463277
TI  - Correction to: Serum DNA integrity index as a potential molecular biomarker in
      endometrial cancer.
AB  - CORRECTION: In the publication of this article [1], there is an error in the
      first sentence of the Acknowledgements section.

PMID- 29463278
TI  - Clinical and radiological effect of medialized cortical bone trajectory for
      lumbar pedicle screw fixation in patients with degenerative lumbar
      spondylolisthesis: study protocol for a randomized controlled trial (mPACT).
AB  - BACKGROUND: Spinal fusion with pedicle screw fixation represents the gold
      standard for lumbar degenerative disc disease with instability. Although it is an
      established technique, it is nevertheless an invasive intervention with high
      complication rates. Therefore, minimally invasive approaches have been developed,
      the medialized bilateral screw pedicel fixation (mPACT) being one of them. The
      study objective is to evaluate prospectively the efficacy and safety of the mPACT
      technique compared with the traditional trajectory for degenerative lumbar
      spondylolisthesis. METHODS/DESIGN: This is a single-center, randomized,
      controlled, parallel group, superiority trial. A total of 154 adult patients are
      allocated in a ratio of 1:1. Sample size and power calculation were performed to
      detect the minimal clinically important difference of 10%, with an expected
      standard deviation of 20% in the primary outcome parameter, the Oswestry
      Disability Index, with power of 80%, based on an assumed maximal dropout rate of
      20%. Secondary outcome parameters include the EuroQoL 5-Dimension questionnaire,
      the Beck Depression Inventory, the painDETECT questionnaire and the "timed up and
      go" test. Furthermore, radiological and health economic outcomes will be
      evaluated. Follow up is performed until 5 years after surgery. Major inclusion
      criteria are lumbar degenerative spondylolisthesis with Meyerding grade I or II,
      which qualifies for decompression and fusion by medialised posterior screw
      placement with cortical trajectory (mPACT) or by a traditional trajectory for
      lumbar pedicle screw placement. DISCUSSION: This trial will contribute to the
      understanding of the short-term and long-term clinical and radiological
      postoperative course in patients with lumbar degenerative disc disease, in which
      the mPACT technique is used. TRIAL REGISTRATION: ISRCTN registry, ISRCTN99263604
      . Registered on 3 November 2016.

PMID- 29463279
TI  - Evaluation of a Chlamydia trachomatis-specific, commercial, real-time PCR for use
      with ocular swabs.
AB  - BACKGROUND: Trachoma, the leading infectious cause of blindness worldwide, is
      caused by conjunctival Chlamydia trachomatis infection. Trachoma is diagnosed
      clinically by observation of conjunctival inflammation and/or scarring; however,
      there is evidence that monitoring C. trachomatis infection may be required for
      elimination programmes. There are many commercial and 'in-house' nucleic acid
      amplification tests for the detection of C. trachomatis DNA, but the majority
      have not been validated for use with ocular swabs. This study evaluated a
      commercial assay, the Fast-Track Vaginal swab kit, using conjunctival samples
      from trachoma-endemic areas. An objective, biostatistical-based method for binary
      classification of continuous PCR data was developed, to limit potential user-bias
      in diagnostic settings. METHODS: The Fast-Track Vaginal swab assay was run on 210
      ocular swab samples from Guinea-Bissau and Tanzania. Fit of individual
      amplification curves to exponential or sigmoid models, derivative and second
      derivative of the curves and final fluorescence value were examined for utility
      in thresholding for determining positivity. The results from the Fast-Track
      Vaginal swab assay were evaluated against a commercial test (Amplicor CT/NG) and
      a non-commercial test (in-house droplet digital PCR), both of whose performance
      has previously been evaluated. RESULTS: Significant evidence of exponential
      amplification (R2 > 0.99) and final fluorescence > 0.15 were combined for
      thresholding. This objective approach identified a population of positive
      samples, however there were a subset of samples that amplified towards the end of
      the cycling protocol (at or later than 35 cycles), which were less clearly
      defined. The Fast-Track Vaginal swab assay showed good sensitivity against the
      commercial (95.71) and non-commercial (97.18) tests. Specificity was lower
      against both (90.00 and 96.55, respectively). CONCLUSIONS: This study defined a
      simple, automated protocol for binary classification of continuous, real-time
      qPCR data, for use in an end-point diagnostic test. This method identified a
      population of positive samples, however, as with manual thresholding, a subset of
      samples that amplified towards the end of the cycling program were less easily
      classified. When used with ocular swabs, the Fast-Track Vaginal swab assay had
      good sensitivity for C. trachomatis detection, but lower specificity than the
      commercial and non-commercial assays it was evaluated against, possibly leading
      to false positives.

PMID- 29463280
TI  - Prophylactic platelet transfusion prior to central venous catheter placement in
      patients with thrombocytopenia: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Severe thrombocytopenia should be corrected by prophylactic platelet
      transfusion prior to central venous catheter (CVC) insertion, according to
      national and international guidelines. Even though correction is thought to
      prevent bleeding complications, evidence supporting the routine administration of
      prophylactic platelets is absent. Furthermore, platelet transfusion bears
      inherent risk. Since the introduction of ultrasound-guided CVC placement,
      bleeding complication rates have decreased. The objective of the current trial
      is, therefore, to demonstrate that omitting prophylactic platelet transfusion
      prior to CVC placement in severely thrombocytopenic patients is non-inferior
      compared to prophylactic platelet transfusion. METHODS/DESIGN: The PACER trial is
      an investigator-initiated, national, multicentre, single-blinded, randomised
      controlled, non-inferior, two-arm trial in haematologic and/or intensive care
      patients with a platelet count of between 10 and 50 * 109/L and an indication for
      CVC placement. Consecutive patients are randomly assigned to either receive 1
      unit of platelet concentrate, or receive no prophylactic platelet transfusion
      prior to CVC insertion. The primary endpoint is WHO grades 2-4 bleeding.
      Secondary endpoints are any bleeding complication, costs, length of intensive
      care and hospital stay and transfusion requirements. DISCUSSION: This is the
      first prospective, randomised controlled trial powered to test the hypothesis of
      whether omitting forgoing platelet transfusion prior to central venous
      cannulation leads to an equal occurrence of clinical relevant bleeding
      complications in critically ill and haematologic patients with thrombocytopenia.
      TRIAL REGISTRATION: Nederlands Trial Registry, ID: NTR5653 (
      http://www.trialregister.nl/trialreg/index.asp ). Registered on 27 January 2016.
      Currently recruiting. Randomisation commenced on 23 February 2016.

PMID- 29463281
TI  - Soluble Abeta1-42 increases the heterogeneity in synaptic vesicle pool size among
      synapses by suppressing intersynaptic vesicle sharing.
AB  - Growing evidence has indicated that prefibrillar form of soluble amyloid beta
      (sAbeta1-42) is the major causative factor in the synaptic dysfunction associated
      with AD. The molecular changes leading to presynaptic dysfunction caused by
      sAbeta1-42, however, still remains elusive. Recently, we found that sAbeta1-42
      inhibits chemically induced long-term potentiation-induced synaptogenesis by
      suppressing the intersynaptic vesicle trafficking through calcium (Ca2+)
      dependent hyperphosphorylation of synapsin and CaMKIV. However, it is still
      unclear how sAbeta1-42 increases intracellular Ca2+ that induces
      hyperphosphorylation of CaMKIV and synapsin, and what is the functional
      consequences of sAbeta1-42-induced defects in intersynaptic vesicle trafficking
      in physiological conditions. In this study, we showed that sAbeta1-42elevated
      intracellular Ca2+ through not only extracellular Ca2+ influx but also Ca2+
      release from mitochondria. Surprisingly, without Ca2+ release from mitochondria,
      sAbeta1-42 failed to increase intracellular Ca2+ even in the presence of normal
      extracellular Ca2+. We further found that sAbeta1-42-induced mitochondria Ca2+
      release alone sufficiently increased Serine 9 phosphorylation of synapsin. By
      blocking synaptic vesicle reallocation, sAbeta1-42 significantly increased
      heterogeneity of total synaptic vesicle pool size among synapses. Together, our
      results suggested that by disrupting the axonal vesicle trafficking, sAbeta1-42
      disabled neurons to adjust synaptic pool sizes among synapses, which might
      prevent homeostatic rescaling in synaptic strength of individual neurons.

PMID- 29463282
TI  - Longitudinal study of age-specific pattern of coronavirus infection in Lyle's
      flying fox (Pteropus lylei) in Thailand.
AB  - BACKGROUND: Bats are natural reservoirs for several highly pathogenic and novel
      viruses including coronaviruses (CoVs) (mainly Alphacoronavirus and
      Betacoronavirus). Lyle's flying fox (Pteropus lylei)'s roosts and foraging sites
      are usually in the proximity to humans and animals. Knowledge about age-specific
      pattern of CoV infection in P. lylei, prevalence, and viral shedding at roosts
      and foraging sites may have an impact on infection-age-structure model to control
      CoV outbreak. METHODS: P. lylei bats were captured monthly during January
      December 2012 for detection of CoV at three areas in Chonburi province; two human
      dwellings, S1 and S2, where few fruit trees were located with an open pig farm,
      0.6 km and 5.5 km away from the bat roost, S3. Nested RT-PCR of RNA-dependent RNA
      polymerase (RdRp) gene from rectal swabs was used for CoV detection. The strain
      of CoV was confirmed by sequencing and phylogenetic analysis. RESULTS: CoV
      infection was found in both juveniles and adult bats between May and October
      (January, in adults only and April, in juveniles only). Of total rectal swab
      positives (68/367, 18.5%), ratio was higher in bats captured at S1 (11/44, 25.0%)
      and S2 (35/99, 35.4%) foraging sites than at roost (S3) (22/224, 9.8%). Juveniles
      (forearm length <= 136 mm) were found with more CoV infection than adults at all
      three sites; S1 (9/24, 37.5% vs 2/20, 10%), S2 (22/49, 44.9% vs 13/50, 26.0%),
      and S3 (10/30, 33.3% vs 12/194, 6.2%). The average BCI of CoV infected bats was
      significantly lower than uninfected bats. No gender difference related to
      infection was found at the sites. Phylogenetic analysis of conserved RdRp gene
      revealed that the detected CoVs belonged to group D betacoronavirus (n = 64) and
      alphacoronavirus (n = 4). CONCLUSIONS: The fact that CoV infection and shedding
      was found in more juvenile than adult bats may suggest transmission from mother
      during peripartum period. Whether viral reactivation during parturition period or
      stress is responsible in maintaining transmission in the bat colony needs to be
      explored.

PMID- 29463283
TI  - Neonatal diagnosis of isolated absence of the right pulmonary artery: a case
      report and review of the literature.
AB  - BACKGROUND: Unilateral absence of the pulmonary artery (UAPA) is a rare
      congenital malformation often associated with other cardiac anomalies; however it
      may occur as an isolated lesion. Isolated absence of the right pulmonary artery
      is twice more frequent than that of the left pulmonary artery. Patients with
      isolated UAPA are usually asymptomatic at birth; thereafter they may develop a
      progression of symptoms such as exercise intolerance, dyspnea, chest pain,
      hemoptysis and recurrent pulmonary infections. As patients may remain
      asymptomatic or have vague symptoms, the diagnosis of isolated UAPA can be
      difficult to make in infancy. Indeed, most cases described in literature are
      adults. Due to the rarity of neonatal presentation, there is no consensus
      regarding the treatment of this malformation. CASE PRESENTATION: Herein, the case
      of a two-day-old term female infant, born after uneventful pregnancy, who
      required a cardiological assessment for a light murmur, is reported; an
      echocardiogram demonstrated an isolated unilateral absence of the right pulmonary
      artery, confirmed by means of magnetic resonance imaging (MRI) performed 1 month
      after child's birth. Besides this finding, MRI showed a slightly increased lumen
      and size of the main and left pulmonary arteries. The right lung was shown to be
      perfused by some systemic collateral arteries. In the absence of any other
      cardiovascular malformation, our patient did not need any treatment. As symptoms
      may occur later in life, a thorough clinical and cardiological follow up was
      immediately started. Three years later, she is still asymptomatic, showing
      adequate growth, without any sign of pulmonary hypertension. CONCLUSIONS:
      Isolated UAPA is a very rare malformation with a diverse clinical presentation.
      To the best of our knowledge, this is the second case of neonatal presentation of
      UAPA reported in literature to date. We believe that our case report supports the
      opinion that a prompt cardiological evaluation is needed whenever a newborn shows
      signs and/or symptoms of cardiorespiratory concern. Any missed neonatal diagnosis
      of UAPA may contribute to the later age at presentation, with resultant higher
      risk of morbidity and mortality and greater therapeutical difficulties.

PMID- 29463284
TI  - The potential role of HGF-MET signaling and autophagy in the war of Alectinib
      versus Crizotinib against ALK-positive NSCLC.
AB  - Non-small-cell lung cancer (NSCLC) is currently the leading cause of cancer
      related death. Accumulating evidences suggest that overcoming the therapeutic
      resistance in NSCLC is a big challenge. Recently, the outcomes of two independent
      phase 3 trials regarding Alectinib versus Crizotinib in ALK-positive NSCLC are
      encouraging. However, given the potential relevance of HGF-MET signaling and
      especially autophagy to the war against ALK-positive NSCLC between Alectinib and
      Crizotinib, it's too early to reach a convincing conclusion. Therefore, to
      further improve the therapeutic efficacy of ALK-positive NSCLC, this commentary
      highlights the negligence in design of relevant clinical trials, emphasizes the
      importance of molecular characteristics investigation, and discusses the prospect
      of combination therapy.

PMID- 29463285
TI  - Network modules uncover mechanisms of skeletal muscle dysfunction in COPD
      patients.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients often show
      skeletal muscle dysfunction that has a prominent negative impact on prognosis.
      The study aims to further explore underlying mechanisms of skeletal muscle
      dysfunction as a characteristic systemic effect of COPD, potentially modifiable
      with preventive interventions (i.e. muscle training). The research analyzes
      network module associated pathways and evaluates the findings using independent
      measurements. METHODS: We characterized the transcriptionally active network
      modules of interacting proteins in the vastus lateralis of COPD patients (n = 15,
      FEV1 46 +/- 12% pred, age 68 +/- 7 years) and healthy sedentary controls (n = 12,
      age 65 +/- 9  years), at rest and after an 8-week endurance training program.
      Network modules were functionally evaluated using experimental data derived from
      the same study groups. RESULTS: At baseline, we identified four COPD specific
      network modules indicating abnormalities in creatinine metabolism, calcium
      homeostasis, oxidative stress and inflammatory responses, showing statistically
      significant associations with exercise capacity (VO2 peak, Watts peak, BODE index
      and blood lactate levels) (P < 0.05 each), but not with lung function (FEV1).
      Training-induced network modules displayed marked differences between COPD and
      controls. Healthy subjects specific training adaptations were significantly
      associated with cell bioenergetics (P < 0.05) which, in turn, showed strong
      relationships with training-induced plasma metabolomic changes; whereas, effects
      of training in COPD were constrained to muscle remodeling. CONCLUSION: In
      summary, altered muscle bioenergetics appears as the most striking finding,
      potentially driving other abnormal skeletal muscle responses. Trial registration
      The study was based on a retrospectively registered trial (May 2017),
      ClinicalTrials.gov identifier: NCT03169270.

PMID- 29463286
TI  - Bronchopulmonary dysplasia: clinical aspects and preventive and therapeutic
      strategies.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is the result of a complex process
      in which several prenatal and/or postnatal factors interfere with lower
      respiratory tract development, leading to a severe, lifelong disease. In this
      review, what is presently known regarding BPD pathogenesis, its impact on long
      term pulmonary morbidity and mortality and the available preventive and
      therapeutic strategies are discussed. MAIN BODY: Bronchopulmonary dysplasia is
      associated with persistent lung impairment later in life, significantly impacting
      health services because subjects with BPD have, in most cases, frequent
      respiratory diseases and reductions in quality of life and life expectancy.
      Prematurity per se is associated with an increased risk of long-term lung
      problems. However, in children with BPD, impairment of pulmonary structures and
      function is even greater, although the characterization of long-term outcomes of
      BPD is difficult because the adults presently available to study have received
      outdated treatment. Prenatal and postnatal preventive measures are extremely
      important to reduce the risk of BPD. CONCLUSION: Bronchopulmonary dysplasia is a
      respiratory condition that presently occurs in preterm neonates and can lead to
      chronic respiratory problems. Although knowledge about BPD pathogenesis has
      significantly increased in recent years, not all of the mechanisms that lead to
      lung damage are completely understood, which explains why therapeutic approaches
      that are theoretically effective have been only partly satisfactory or useless
      and, in some cases, potentially negative. However, prevention of prematurity,
      systematic use of nonaggressive ventilator measures, avoiding supraphysiologic
      oxygen exposure and administration of surfactant, caffeine and vitamin A can
      significantly reduce the risk of BPD development. Cell therapy is the most
      fascinating new measure to address the lung damage due to BPD. It is desirable
      that ongoing studies yield positive results to definitively solve a major
      clinical, social and economic problem.

PMID- 29463287
TI  - Weaved into the cultural fabric: a qualitative exploration of alcohol consumption
      during pregnancy among tribal women in Odisha, India.
AB  - BACKGROUND: Evidence-based research has documented the association between
      alcohol intake during pregnancy and increased risk of miscarriage, stillbirth and
      congenital birth defects. Alcohol consumption is a complex behavior whose origins
      lay in cultural norms and the social structure. In tribal communities in India,
      alcohol misuse among women is a public health problem. This study is intended to
      explore perceptions and beliefs among tribal women and the community towards
      alcohol consumption during pregnancy. METHODS: A qualitative study was conducted
      in a tribal-dominated district of Odisha, India. The WHO AUDIT tool was used to
      identify women who consumed alcohol during their pregnancies. In-depth interviews
      were conducted with 19 eligible women and 18 family members. Additionally, two
      focused group discussions were held with local community leaders and health
      workers. The data was transcribed, systematically coded and analyzed following
      the thematic framework approach. RESULTS: The findings suggest that a complex
      interplay of drivers contributes to the unrestricted intake of alcohol by
      pregnant women. This could be attributed to: a lack of social monitoring, easy
      access to alcohol, low alcohol literacy and alcohol's normative status in daily
      customs and traditions. Another contributing factor is a community-wide
      perception that home-made alcohol poses no ill effects. CONCLUSION: Alcohol
      consumption is deeply embedded in the daily rituals of indigenous tribal women.
      To address this issue, community counselling utilizing platforms of RMNCHA and
      VHND could be Ideal. A well-designed, culture-based intervention encompassing
      alcohol researchers, mental health specialists, public health workers and
      anthropologists is necessary.

PMID- 29463288
TI  - Reactive community-based self-administered treatment against residual malaria
      transmission: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Systematic treatment of all individuals living in the same compound
      of a clinical malaria case may clear asymptomatic infections and possibly reduce
      malaria transmission, where this is focal. High and sustained coverage is
      extremely important and requires active community engagement. This study explores
      a community-based approach to treating malaria case contacts. METHODS/DESIGN:
      This is a cluster-randomized trial to determine whether, in low-transmission
      areas, treating individuals living in the same compound of a clinical malaria
      case with dihydroartemisinin-piperaquine can reduce parasite carriage and thus
      residual malaria transmission. Treatment will be administered through the local
      health system with the approach of encouraging community participation designed
      and monitored through formative research. The trial goal is to show that this
      approach can reduce in intervention villages the prevalence of Plasmodium
      falciparum infection toward the end of the malaria transmission season.
      DISCUSSION: Adherence and cooperation of the local communities are critical for
      the success of mass treatment campaigns aimed at reducing malaria transmission.
      By exploring community perceptions of the changing trends in malaria burden,
      existing health systems, and reaction to self-administered treatment, this study
      will develop and adapt a model for community engagement toward malaria
      elimination that is cost-effective and fits within the existing health system.
      TRIAL REGISTRATION: Clinical trials.gov, NCT02878200 . Registered on 25 August
      2016.

PMID- 29463289
TI  - Strain-dependent effects of clinical echovirus 30 outbreak isolates at the blood
      CSF barrier.
AB  - BACKGROUND: Echovirus (E) 30 (E-30) meningitis is characterized by
      neuroinflammation involving immune cell pleocytosis at the protective barriers of
      the central nervous system (CNS). In this context, infection of the blood
      cerebrospinal fluid barrier (BCSFB), which has been demonstrated to be involved
      in enteroviral CNS pathogenesis, may affect the tight junction (TJ) and adherens
      junction (AJ) function and morphology. METHODS: We used an in vitro human choroid
      plexus epithelial (HIBCPP) cell model to investigate the effect of three clinical
      outbreak strains (13-311, 13-759, and 14-397) isolated in Germany in 2013, and
      compared them to E-30 Bastianni. Conducting transepithelial electrical resistance
      (TEER), paracellular dextran flux measurement, quantitative real-time polymerase
      chain reaction (qPCR), western blot, and immunofluorescence analysis, we
      investigated TJ and AJ function and morphology as well as strain-specific E-30
      infection patterns. Additionally, transmission electron and focused ion beam
      microscopy electron microscopy (FIB-SEM) was used to evaluate the mode of
      leukocyte transmigration. Genome sequencing and phylogenetic analyses were
      performed to discriminate potential genetic differences among the outbreak
      strains. RESULTS: We observed a significant strain-dependent decrease in TEER
      with strains E-30 Bastianni and 13-311, whereas paracellular dextran flux was
      only affected by E-30 Bastianni. Despite strong similarities among the outbreak
      strains in replication characteristics and particle distribution, strain 13-311
      was the only outbreak isolate revealing comparable disruptive effects on TJ
      (Zonula Occludens (ZO) 1 and occludin) and AJ (E-cadherin) morphology to E-30
      Bastianni. Notwithstanding significant junctional alterations upon E-30
      infection, we observed both para- and transcellular leukocyte migration across
      HIBCPP cells. Complete genome sequencing revealed differences between the strains
      analyzed, but no explicit correlation with the observed strain-dependent effects
      on HIBCPP cells was possible. CONCLUSION: The findings revealed distinct E-30
      strain-specific effects on barrier integrity and junctional morphology. Despite E
      30-induced barrier alterations leukocyte trafficking did not exclusively occur
      via the paracellular route.

PMID- 29463290
TI  - Transcranial Doppler combined with quantitative EEG brain function monitoring and
      outcome prediction in patients with severe acute intracerebral hemorrhage.
AB  - BACKGROUND: Neurological deterioration after intracerebral hemorrhage (ICH) is
      thought to be closely related to increased intracranial pressure (ICP), decreased
      cerebral blood flow (CBF), and brain metabolism. Transcranial Doppler (TCD) is
      increasingly used as an indirect measure of ICP, and quantitative EEG (QEEG) can
      reflect the coupling of CBF and metabolism. We aimed to combine TCD and QEEG to
      comprehensively assess brain function after ICH and provide prognostic diagnosis.
      METHODS: We prospectively enrolled patients with severe acute supratentorial
      (SAS)-ICH from June 2015 to December 2016. Mortality was assessed at 90-day
      follow-up. We collected demographic data, serological data, and clinical factors,
      and performed neurophysiological tests at study entry. Quantitative brain
      function monitoring was performed using a TCD-QEEG recording system at the
      patient's bedside (NSD-8100; Delica, China). Univariate and multivariable
      analyses and receiver operating characteristic (ROC) curves were employed to
      assess the relationships between variables and outcome. RESULTS: Forty-seven
      patients (67.3 +/- 12.6 years; 23 men) were studied. Mortality at 90 days was
      55.3%. Statistical results showed there were no significant differences in brain
      symmetry index between survivors and nonsurvivors, nor between patients and
      controls (all p > 0.05). Only TCD indicators of the pulsatility index from
      unaffected hemispheres (UPI) (OR 2.373, CI 1.299-4.335, p = 0.005) and QEEG
      indicators of the delta/alpha ratio (DAR) (OR 5.306, CI 1.533-18.360, p = 0.008)
      were independent predictors for clinical outcome. The area under the ROC curve
      after the combination of UPI and DAR was 0.949, which showed better predictive
      accuracy compared to individual variables. CONCLUSIONS: In patients with SAS-ICH,
      multimodal neuromonitoring with TCD combined with QEEG indicated that brain
      damage caused diffuse changes, and the predictive accuracy after combined use of
      TCD-QEEG was statistically superior in performance to any single variable,
      whether clinical or neurophysiological.

PMID- 29463291
TI  - Hypertonic saline infusion for treating intracranial hypertension after severe
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) remains a major cause of mortality and disability.
      Post-traumatic intracranial hypertension (ICH) further complicates the care of
      patients. Hyperosmolar agents are recommended for the treatment of ICH, but no
      consensus or high-level data exist on the use of any particular agent or the
      route of administration. The two agents used commonly are hypertonic saline (HTS)
      and mannitol given as bolus therapy. Smaller studies suggest that HTS may be a
      superior agent in reducing the ICH burden, but neither agent has been shown to
      improve mortality or functional outcome. In a recently published analysis of
      pooled data from three prospective clinical trials, continuous infusion of HTS
      correlated with serum hypernatremia and reduced ICH burden in addition to
      improving 90-day mortality and functional outcome. This lays the foundation for
      the upcoming continuous hyperosmolar therapy for traumatic brain-injured patients
      (COBI) randomized controlled trial to study the outcome benefit of continuous HTS
      infusion to treat ICH after severe TBI. This is much anticipated and will be a
      high impact trial should the results be replicated. However, this would still
      leave a question over the use of mannitol bolus therapy which will need to be
      studied.

PMID- 29463292
TI  - Effectiveness of interventions aimed at improving physical and psychological
      outcomes of fall-related injuries in people with dementia: a narrative systematic
      review.
AB  - BACKGROUND: The annual prevalence of falls in people with dementia ranges from 47
      to 90%. Falls are a common reason for hospital admission in people with dementia,
      and there is limited research evidence regarding the care pathways experienced by
      this population. In addition to immediate management of an injury, prevention of
      further falls is likely to be an important part of any successful intervention.
      This review aims to assess the effectiveness of interventions for improving the
      physical and psychological wellbeing of people with dementia who have sustained a
      fall-related injury. METHODS: Systematic review methodologies were employed
      utilising searches across multiple databases (MEDLINE, CENTRAL, Health Management
      Information Consortium, EMBASE, CINAHL, Web of Science, Allied and Complementary
      Medicine Database, and Physiotherapy Evidence Database (PEDro)) and citation
      chaining. Studies including people with a known diagnosis of dementia living in
      the community and who present at health services with a fall, with or without
      injury, were included. Outcomes of interest included mobility, recurrent falls,
      activities of daily living, length of hospital stay, and post-discharge
      residence. Results were independently reviewed and quality assessed by two
      researchers, and data extracted using a customised form. A narrative synthesis
      was performed due to heterogeneity of the included studies. RESULTS: Seven
      studies were included. Interventions clustered into three broad categories:
      multidisciplinary in-hospital post-surgical geriatric assessment;
      pharmaceuticals; and multifactorial assessment. Multidisciplinary care and early
      mobilisation showed short-term improvements for some outcomes. Only an annual
      administration of zoledronic acid showed long-term reduction in recurrent falls.
      CONCLUSIONS: Due to high heterogeneity across the studies, definitive conclusions
      could not be reached. Most post-fall interventions were not aimed at patients
      with dementia and have shown little efficacy regardless of cognitive status.
      Minor improvements to some quality of life indicators were shown, but these were
      generally not statistically significant. Conclusions were also limited due to
      most studies addressing hip fracture; the interventions provided for this type of
      injury may not be suitable for other types of fractures or soft tissue injuries,
      or for use in primary care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42016029565 .

PMID- 29463293
TI  - Co-infection of intestinal parasites and Helicobacter pylori among upper
      gastrointestinal symptomatic adult patients attending Mekanesalem Hospital,
      northeast Ethiopia.
AB  - OBJECTIVE: Intestinal parasites and H. pylori are well-known for their high
      prevalence worldwide. Thus, the objective of this study waste assess risk factors
      and co-infection of intestinal parasites and H. pylori among adult patients with
      upper gastrointestinal complaints. A hospital-based cross sectional study was
      conducted among 363 consecutive adult patients from December 10, 2015 to February
      30,2016. Stool and venous blood were collected for analysis of Intestinal
      parasites and H. pylori infection, respectively. Data was analyzed using SPSS
      version 16 and logistic regression analysis was carried out to assess predictors
      of co-infection. A p <= 0.05 was considered as statistically significant.
      RESULTS: Helicobacter pylori IgG and intestinal parasites were detected in 70.25
      38.3% of participants, respectively while G. lamblia accounted 22.3%. G. lamblia
      prevalence was significantly higher among H. pylori infected participants (COR:
      2.76; 95% CI: 1.46-5.23), but E. hystolytica/dispar infection didn't show
      significant variation (p = 0.15). H. pylori and intestinal parasites concomitant
      co-infection was associated with male sex (AOR: 1.61; 95% CI: 1.01-2.56),
      consumption of river water (AOR: 1.85; 95% CI: 1.11-3.07) and ground/spring water
      (AOR: 4.10; 95% CI: 1.97-8.52). Thus, besides H. pylori investigation, upper
      gastrointestinal symptomatic patients should be screened for G. lamblia infection
      and other intestinal parasites.

PMID- 29463294
TI  - Rare variant of metaplastic carcinoma of the breast: a case report and review of
      the literature.
AB  - BACKGROUND: Metaplastic carcinoma encompasses a group of neoplasms characterized
      by differentiation of the neoplastic epithelium into squamous cells and/or
      mesenchymal-looking elements. Spindle cell carcinoma is a rare variant of this
      special histological type. Its prognosis remains poor, with a high rate of local
      recurrence and distant metastasis. To date, only a small number of cases have
      been described. There is no clear agreement on this histological subtype. CASE
      PRESENTATION: We report a case of a 53-year-old Moroccan woman who consulted our
      institution following palpation of a nodule of the left breast. Mammography in
      combination with breast ultrasonography revealed a lesion classified as Breast
      Imaging Reporting and Data System 4 with microcalcification. The patient was
      diagnosed with spindle cell carcinoma of the breast. The diagnosis was based
      primarily on histological and immunohistochemical studies of the breast biopsy
      and secondarily on the surgical specimen. No local or distant metastasis was
      found. The treatment used was total surgical excision followed by radiotherapy.
      CONCLUSIONS: We describe the features (epidemiological, clinical, histological,
      immunohistochemical, and therapeutic outcomes) of our patient's case and compare
      them with literature data.

PMID- 29463295
TI  - Thermal regime and host clade, rather than geography, drive Symbiodinium and
      bacterial assemblages in the scleractinian coral Pocillopora damicornis sensu
      lato.
AB  - BACKGROUND: Although the term holobiont has been popularized in corals with the
      advent of the hologenome theory of evolution, the underlying concepts are still a
      matter of debate. Indeed, the relative contribution of host and environment and
      especially thermal regime in shaping the microbial communities should be examined
      carefully to evaluate the potential role of symbionts for holobiont adaptation in
      the context of global changes. We used the sessile, long-lived, symbiotic and
      environmentally sensitive reef-building coral Pocillopora damicornis to address
      these issues. RESULTS: We sampled Pocillopora damicornis colonies corresponding
      to two different mitochondrial lineages in different geographic areas displaying
      different thermal regimes: Djibouti, French Polynesia, New Caledonia, and Taiwan.
      The community composition of bacteria and the algal endosymbiont Symbiodinium
      were characterized using high-throughput sequencing of 16S rRNA gene and internal
      transcribed spacer, ITS2, respectively. Bacterial microbiota was very diverse
      with high prevalence of Endozoicomonas, Arcobacter, and Acinetobacter in all
      samples. While Symbiodinium sub-clade C1 was dominant in Taiwan and New
      Caledonia, D1 was dominant in Djibouti and French Polynesia. Moreover, we also
      identified a high background diversity (i.e., with proportions < 1%) of A1, C3,
      C15, and G Symbiodinum sub-clades. Using redundancy analyses, we found that the
      effect of geography was very low for both communities and that host genotypes and
      temperatures differently influenced Symbiodinium and bacterial microbiota.
      Indeed, while the constraint of host haplotype was higher than temperatures on
      bacterial composition, we showed for the first time a strong relationship between
      the composition of Symbiodinium communities and minimal sea surface temperatures.
      CONCLUSION: Because Symbiodinium assemblages are more constrained by the thermal
      regime than bacterial communities, we propose that their contribution to adaptive
      capacities of the holobiont to temperature changes might be higher than the
      influence of bacterial microbiota. Moreover, the link between Symbiodinium
      community composition and minimal temperatures suggests low relative fitness of
      clade D at lower temperatures. This observation is particularly relevant in the
      context of climate change, since corals will face increasing temperatures as well
      as much frequent abnormal cold episodes in some areas of the world.

PMID- 29463297
TI  - Implementation of a competency-based medical education approach in public health
      and epidemiology training of medical students.
AB  - BACKGROUND: There is increasing agreement among medical educators regarding the
      importance of improving the integration between public health and clinical
      education, understanding and implementation of epidemiological methods, and the
      ability to critically appraise medical literature. The Sackler School of Medicine
      at Tel-Aviv University revised its public health and preventive medicine
      curriculum, during 2013-2014, according to the competency-based medical education
      (CBME) approach in training medical students. We describe the revised curriculum,
      which aimed to strengthen competencies in quantitative research methods,
      epidemiology, public health and preventive medicine, and health service
      organization and delivery. METHODS: We report the process undertaken to establish
      a relevant 6-year longitudinal curriculum and describe its contents,
      implementation, and continuous assessment and evaluation. RESULTS: Central
      competencies included: epidemiology and statistics for appraisal of the
      literature and implementation of research; the application of health promotion
      principles and health education strategies in disease prevention; the use of an
      evidence-based approach in clinical and public health decision making; the
      examination and analysis of disease trends at the population level; and knowledge
      of the structure of health systems and the role of the physician in these
      systems. Two new courses, in health promotion, and in public health, were added
      to the curriculum, and the courses in statistics and epidemiology were joined.
      Annual evaluation of each course results in continuous revisions of the syllabi
      as needed, while we continue to monitor the whole curriculum. CONCLUSIONS: The
      described revision in a 6 year-medical school training curriculum addresses the
      currently identified needs in public health. Ongoing feedback from students, and
      re-evaluation of syllabus by courses teams are held annually. Analysis of
      student's written feedbacks and courses evaluations of "before and after" the
      implementation of this intervention is taking place to examine the effect of the
      new curriculum on the perceived clinical and research capacities of our 6-year
      students.

PMID- 29463296
TI  - Nilotinib impairs skeletal myogenesis by increasing myoblast proliferation.
AB  - BACKGROUND: Tyrosine kinase inhibitors (TKIs) are effective therapies with
      demonstrated antineoplastic activity. Nilotinib is a second-generation FDA
      approved TKI designed to overcome Imatinib resistance and intolerance in patients
      with chronic myelogenous leukemia (CML). Interestingly, TKIs have also been shown
      to be an efficient treatment for several non-malignant disorders such fibrotic
      diseases, including those affecting skeletal muscles. METHODS: We investigated
      the role of Nilotinib on skeletal myogenesis using the well-established C2C12
      myoblast cell line. We evaluated the impact of Nilotinib during the time course
      of skeletal myogenesis. We compared the effect of Nilotinib with the well-known
      p38 MAPK inhibitor SB203580. MEK1/2 UO126 and PI3K/AKT LY294002 inhibitors were
      used to identify the signaling pathways involved in Nilotinib-related effects on
      myoblast. Adult primary myoblasts were also used to corroborate the inhibition of
      myoblasts fusion and myotube-nuclei positioning by Nilotinib. RESULTS: We found
      that Nilotinib inhibited myogenic differentiation, reducing the number of
      myogenin-positive myoblasts and decreasing myogenin and MyoD expression.
      Furthermore, Nilotinib-mediated anti-myogenic effects impair myotube formation,
      myosin heavy chain expression, and compromise myotube-nuclei positioning. In
      addition, we found that p38 MAPK is a new off-target protein of Nilotinib, which
      causes inhibition of p38 phosphorylation in a similar manner as the well
      characterized p38 inhibitor SB203580. Nilotinib induces the activation of ERK1/2
      and AKT on myoblasts but not in myotubes. We also found that Nilotinib stimulates
      myoblast proliferation, a process dependent on ERK1/2 and AKT activation.
      CONCLUSIONS: Our findings suggest that Nilotinib may have important negative
      effects on muscle homeostasis, inhibiting myogenic differentiation but
      stimulating myoblasts proliferation. Additionally, we found that Nilotinib
      stimulates the activation of ERK1/2 and AKT. On the other hand, we suggest that
      p38 MAPK is a new off-target of Nilotinib. Thus, there is a necessity for future
      studies to investigate the long-term effects of TKIs on skeletal muscle
      homeostasis, along with potential detrimental effects in cell differentiation and
      proliferation in patients receiving TKI therapies.

PMID- 29463298
TI  - Registration of systematic reviews in PROSPERO: 30,000 records and counting.
AB  - BACKGROUND: The International Prospective Register of Systematic Reviews
      (PROSPERO) was launched in February 2011 to increase transparency of systematic
      reviews (SRs). There have been few investigations of the content and use of the
      database. We aimed to investigate the number of PROSPERO registrations from
      inception to 2017, and website usage in the last year. We also aimed to explore
      the epidemiological characteristics of and completeness of primary outcome pre
      specification in a sample of PROSPERO records from 2017. METHODS: The PROSPERO
      database managers provided us with data on the annual and cumulative number of SR
      registrations up to October 10, 2017, and the number of visits to the PROSPERO
      website over the year preceding October 10, 2017. One author collected data on
      the focus of the SR (e.g. therapeutic, diagnostic), health area addressed,
      funding source and completeness of outcome pre-specification in a random sample
      of 150 records of SRs registered in PROSPERO between April 1, 2017 and September
      30, 2017. RESULTS: As of October 10, 2017, there were 26,535 SRs registered in
      PROSPERO; guided by current monthly submission rates, we anticipate this figure
      will reach over 30,000 by the end of 2017. There has been a 10-fold increase in
      registrations, from 63 SRs per month in 2012 to 800 per month in 2017. In the
      year preceding October 10, 2017, the PROSPERO website received more than 1.75
      million page views. In the random sample of 150 registered SRs, the majority were
      focused on a therapeutic question (78/150 [52%]), while only a few focused on a
      diagnostic/prognostic question (11/150 [7%]). The 150 registered SRs addressed 18
      different health areas. Any information about the primary outcome other than the
      domain (e.g. timing, effect measures) was not pre-specified in 44/150 records
      (29%). CONCLUSIONS: Registration of SRs in PROSPERO increased rapidly between
      2011 and 2017, thus benefiting users of health evidence who want to know about
      ongoing SRs. Further work is needed to explore how closely published SRs adhere
      to the planned methods, whether greater pre-specification of outcomes prevents
      selective inclusion and reporting of study results, and whether registered SRs
      address necessary questions.

PMID- 29463299
TI  - Risk factors associated with precancerous cervical lesion among women screened at
      Marie Stops Ethiopia, Adama town, Ethiopia 2017: a case control study.
AB  - OBJECTIVE: Although cervical cancer is a preventable disease, it remains a
      leading cause of death among women in developing countries. In this unmatched
      case control design, 55 cases and 109 controls were included. The main objective
      of this study was to assess the risk factors of precancerous cervical lesion in
      Adama town. RESULTS: A total of 164 participants were recruited in this study. Of
      the 109 controls, 64 (61%) and 41 (39%) of cases were using oral contraception.
      Women who were using oral contraception were two times at risk for developing
      precancerous cervical lesion than who were not using (COR = 2.059 95% CI 1.006,
      4.216; AOR = 2.342). Out of 55 cases, 21 (38.2%) cases had a history STI and out
      of 109 controls, 24 (22.2%) controls had a history of STI. It was revealed that
      STI has a significant association for developing of precancerous lesion. Women
      who had a history of STI were two times at risk of developing precancerous
      cervical lesion than who had no (COR = 2.187; AOR = 2.485). It was found that
      initiation of sexual intercourse before the age of 15 years has 5.6 risks to
      develop precancerous cervical lesion (COR = 5.625 AOR = 6.703).

PMID- 29463300
TI  - Effectiveness of a field trap barrier system for controlling Aedes albopictus: a
      "removal trapping" strategy.
AB  - BACKGROUND: Aedes aegypti and Aedes albopictus are the main vectors for the
      transmission of several viral pathogens, in particular, dengue, Zika and
      chikungunya. In the absence of vaccines and treatment, control of Aedes
      mosquitoes is the only means of keeping these diseases in check. Aedes control is
      difficult, and it is, therefore, necessary to evaluate the efficacy of novel
      control methods, particularly those targeting adult and exophilic Ae. albopictus
      populations. METHODS: We carried out the first evaluation of the effectiveness of
      a field trap barrier system, i.e. a "removal trapping" outdoor control strategy
      for Ae. albopictus in southern France. RESULTS: The removal trapping control
      strategy is an effective system, able to reduce to almost zero the biting rate of
      the tiger mosquito in and around houses with traps installed. This strategy has
      the advantage of being a non-chemical method, which is environmentally friendly
      and does not affect non-target fauna. Nevertheless, it has several constraints
      including the cost of the CO2 required for the system to function. However, the
      system could be optimized by reducing the costs and combining it with other
      control strategies within the framework of integrated vector management.
      CONCLUSIONS: We provide the first evidence of the effectiveness of this trap
      barrier system, which is based on the combined effect of (i) removing adult
      mosquitoes living in the area, and (ii) hampering the migration of mosquitoes
      from outside into the treated area. Further investigation is needed to understand
      its efficacy for other species, other locations and at-risk communities, and to
      evaluate its application for reducing the prevalence of dengue, Zika and
      chikungunya diseases.

PMID- 29463301
TI  - Molecular detection of colistin resistance genes (mcr-1 to mcr-5) in human
      vaginal swabs.
AB  - OBJECTIVE: Colistin resistance has emerged worldwide and has been threatening the
      efficacy of one of the last-resort antimicrobials used for treatment of multidrug
      resistant Gram-negative bacteria. While five colistin resistance genes (mcr-1,
      mcr-2, mcr-3, mcr-4 and mcr-5) have been described, few data are available on the
      prevalence of mcr-genes other than mcr-1 in human samples. RESULTS: In this
      study, the presence of five currently described colistin resistance genes (mcr 1
      5) in vaginal swabs of women undergoing infertility evaluation was reported. Most
      samples were found to be positive for the mcr-4 (12.7%), followed by two for the
      mcr-2 (1.5%), two for the mcr-3 (1.5%), one for the mcr-1 (0.7%), and one for the
      mcr-5 (0.7%). Phylogenetic comparison demonstrated identical (mcr-1, mcr-2, mcr
      3, mcr-5) or similar (mcr-4) nucleotide sequences of human samples and those of
      animal origins from the same city, suggesting the potential transmission of mcr
      genes from animals to humans. This is the first detection of mcr-2, mcr-4 and mcr
      5 genes in human samples, and warrants further research to determine the spread
      of the mcr genes and elucidate the full epidemiology of colistin resistance genes
      in humans.

PMID- 29463302
TI  - The impact of PD-L1 on survival and value of the immune check point inhibitors in
      non-small-cell lung cancer; proposal, policies and perspective.
AB  - BACKGROUND: The impact of programmed death receptor-ligand1 (PD-L1) on costs and
      value of the immune check point inhibitors (ICPI) has received minimal attention.
      OBJECTIVES: 1- Design a sliding scale to grade survival in 2nd-line non-small
      cell lung cancer (NSCLC). 2- Compare costs and value of Nivolumab (Nivo),
      Atezolizumab (Atezo) and Pembrolizumab (Pembro) vs. Docetaxel (Doc). METHODS:
      Previously reported median overall survival (OS) and prices posted by parent
      company were utilized. The OS gains over controls in days were graded (gr) from
      A+ to D. Docetaxel costs were calculated for 6-12 cycles and the ICPI for 1 year.
      Adverse events treatment costs (AEsTC) were reported separately. The cost/life
      year gain (C/LYG) was computed as drug yearly-cost/OS gain over control in days *
      360 days. The relative value of the ICPI were expressed as $100,000/C/LYG.
      RESULTS: Costs of Doc 6 cycles were $23,868, OS/gr 87/C, AEs gr 3/4 > 20%, AEsTC
      $1978 and 6- 12 cycle C/LYG $98,764 -$197,528. Nivo, Atezo and Pembro gr 3/4 were
      < 20% at average costs of $1480. In non-squamous NSCLC, Nivo demonstrated OS/g
      84/C and C/LYG $558,326 as compared with 264/A and $177,645 in PD-L1 > 10%.
      Atezolizumab OS/g were 87/B and C/LYG $551,407 improving in enriched PD-L1 to
      162/A and $332,020 respectively. Pembrolizumab in PD-L1 > 1.0% demonstrated OS/g
      57/C and C/LYG $659,059 improving in > 50% PD-L1 to 201/A and $186,897. PD-L1
      enrichment increased RV of Nivo from 0.18 to 0.56, Atezo from 0.16 to 0.66 and
      Pembro from 0.15 to 0.53. CONCLUSIONS: Simplified methodology to grade OS and
      weigh value of anticancer drugs was proposed. In 2nd-line non-squamous NSCLC,
      value of Doc, Nivo, Atezo and Pembro regardless of PDL-1 expression were limited
      and modest. Enrichment of PD-L1 resulted in unprecedented OS, improved grades and
      enhanced value at seemingly justifiable costs.

PMID- 29463303
TI  - Development and evaluation of 16 new microsatellite loci for the rock ptarmigan
      (Lagopus muta) and cross-species amplification for the willow grouse (L.
      lagopus).
AB  - OBJECTIVE: The genetic markers designed for this study can facilitate future
      genetic studies on the rock ptarmigan (Lagopus muta). To our knowledge no
      microsatellite markers have ever been developed specifically for this species
      before. These new microsatellite markers will be useful for population genetics
      studies and for future conservation projects. RESULTS: Using Next Generation
      Sequencing 6252 potential microsatellite sequences were found. Sixteen
      nonpalindromic tetranucleotide microsatellites and their respective primers were
      selected. The markers were tested on both the rock ptarmigan and the willow
      grouse (L. lagopus). The number of alleles varied between 2 and 18 for the rock
      ptarmigan, and between 3 and 13 for the willow grouse. Expected heterozygosity
      was in the range 0.1244-0.8692 and 0.1358-0.8722 for the rock ptarmigan and the
      willow grouse, respectively.

PMID- 29463304
TI  - Schistosoma mansoni and other intestinal parasitic infections in schoolchildren
      and vervet monkeys in Lake Ziway area, Ethiopia.
AB  - OBJECTIVE: To assess Schistosoma mansoni and other intestinal parasitic
      infections in schoolchildren and vervet monkeys (Chlorocebus aethiops) in
      Bochessa Village, Ziway, Ethiopia. RESULTS: Fecal specimens from selected
      schoolchildren and droppings of the vervet monkeys were collected and
      microscopically examined for intestinal parasites using the Kato-Katz thick smear
      and formol-ether concentration techniques. The prevalences of S. mansoni,
      Trichuris trichiura, Ascaris lumbricoides, Enterobius vermicularis, hookworms,
      Hymenolepis nana and Taenia species among the children were 35.7, 26.9, 24.1,
      2.1, 2.1, 1.07 and 2.1%, respectively (by Kato-Katz) and 39.3, 36.1, 35.6, 2.9,
      10.0, 4.3, and 2.9%, respectively (by formol-ether concentration). Prevalence of
      S. mansoni in vervet monkeys ranged from 10 to 20%. B. pfeifferi snails were
      exposed to S. mansoni miracidia from vervet origin, shed cercariae were then used
      to infect lab-bred albino mice. Adult worms were harvested from the mice 5 weeks
      post-exposure to cercariae to establish the schistosome life cycle and confirm
      the infection in the vervet monkeys. The natural infection of S. mansoni in
      vervet monkeys suggests that the non-human primate is likely to be implicated in
      the local transmission of schistosomiasis. Further epidemiological and molecular
      studies are needed to fully elucidate zoonotic role of non-human primate in the
      area.

PMID- 29463305
TI  - Lysozyme improves gut performance and protects against enterotoxigenic
      Escherichia coli infection in neonatal piglets.
AB  - Diarrhea remains one of the leading causes of morbidity and mortality globally,
      with enterotoxigenic Escherichia coli (ETEC) constituting a major causative
      pathogen. The development of alternative treatments for diarrhea that do not
      involve chemotherapeutic drugs or result in antibiotic resistance is critical.
      Considering that lysozyme is a naturally occurring antimicrobial peptide, in a
      previous study we developed a transgenic pig line that expresses recombinant
      human lysozyme (hLZ) in its milk. In the present study, we examined the
      protective effects of the consumption of this milk against ETEC infection in
      neonatal piglets. We found that consuming hLZ milk facilitated faster recovery
      from infection and decreased mortality and morbidity following an ETEC oral
      inoculation or infection acquired by contact-exposure. The protective effect of
      hLZ was associated with the enrichment of intestinal bacteria that improve gut
      health, such as Lactobacillus, and the enhancement of the mucosal IgA response to
      the ETEC-induced diarrhea. Our study revealed potential protective mechanisms
      underlying the antimicrobial activity of human lysozyme, validating the use of
      lysozyme as an effective preventive measure for diarrhea.

PMID- 29463306
TI  - Fanconi anemia core complex-dependent HES1 mono-ubiquitination regulates its
      transcriptional activity.
AB  - OBJECTIVE: The Hairy Enhancer of Split 1 (HES1) is a transcriptional repressor
      that regulates cellular proliferation and differentiation during development. We
      previously found an interaction between HES1 and Fanconi anemia (FA) proteins. FA
      is a hematological and developmental disorder caused by mutations in more than 20
      different genes. Eight FA gene products form a nuclear core complex containing E3
      ligase activity required for mono-ubiquitination of FANCD2 and FANCI, both of
      which are FA proteins. Given that HES1 interacts with members of the FA core
      complex, the aim of this study was to determine whether HES1 is mono
      ubiquitinated via the FA core complex. RESULTS: We show that HES1 is mono
      ubiquitinated on a highly-conserved lysine residue that is located within a FA
      like recognition motif. HES1 modification is dependent on a functional FA
      complex. Absence of HES1 mono-ubiquitination affects transcriptional repression
      of its own promoter. This study uncovers a novel post-translational modification
      of HES1 that regulates its transcriptional activity and suggests that
      ubiquitination of HES1 occurs in a FA core complex-dependent manner.

PMID- 29463307
TI  - How elimination of lymphatic filariasis as a public health problem in the Kingdom
      of Cambodia was achieved.
AB  - BACKGROUND: Endemicity of lymphatic filariasis (LF) in Cambodia was proven in
      1956 when microfilariae were detected in mosquitos in the Kratie province. In
      2001, an extensive study confirmed the presence of both Brugia malayi and
      Wuchereria bancrofti microfilariae. In 2003, the Ministry of Health established a
      national task force to develop policies and strategies for controlling and
      eliminating neglected tropical diseases (NTDs), with the goal of eliminating LF
      by 2015. This article summarizes the work accomplished to eliminate LF as a
      public health problem in Cambodia. METHODS: The National Program to Eliminate
      Lymphatic Filariasis made excellent progress in the goal towards elimination due
      to strong collaboration between ministries, intensive supervision by national
      staff, and advocacy for mobilization of internal and external resources. Mass
      drug administration (MDA) with diethylcarbamazine citrate and albendazole was
      conducted in six implementation units, achieving > 70% epidemiological coverage
      for five consecutive rounds, from 2005 to 2009. In 2006, in 14 provinces,
      healthcare workers developed a line list of lymphedema and hydrocele patients,
      many of whom were > 40 years old and had been affected by LF for many years. The
      national program also trained healthcare workers and provincial and district
      staff in morbidity management and disability prevention, and designated health
      centers to provide care for lymphedema and acute attack. Two reference hospitals
      were designated to administer hydrocele surgery. RESULTS: Effectiveness of MDA
      was proven with transmission assessment surveys. These found that less than 1% of
      school children had antigenemia in 2010, which fell to 0% in both 2013 and 2015.
      A separate survey in one province in 2015 using Brugia Rapid tests to test for LF
      antibody found one child positive among 1677 children. The list of chronic LF
      patients was most recently updated and confirmed in 2011-2012, with 32
      lymphoedema patients and 17 hydrocele patients listed. All lymphedema patients
      had been trained on self-management and all hydrocele patients had been offered
      free surgery. CONCLUSIONS: Due to the success of the MDA and the development of
      health center capacity for patient care, along with benefits gained from
      socioeconomic improvements and other interventions against vector-borne diseases
      and NTDs, Cambodia was validated by the World Health Organization as achieving LF
      elimination as a public health problem in 2016.

PMID- 29463309
TI  - Zanthoxylum armatum DC extracts from fruit, bark and leaf induce hypolipidemic
      and hypoglycemic effects in mice- in vivo and in vitro study.
AB  - BACKGROUND: Zanthoxylum armatum DC is an important medicinal plant of south East
      Asia, and has been used to treat various ailments in traditional medicine
      including diabetes. This study investigated the in vitro and in vivo antidiabetic
      and biochemical effects of extracts of Z. armatum in mice. METHOD: The extracts
      of fruit, bark and leaf from Z. armatum were tested for alpha-glucosidase
      inhibition activity. Albino mice of either sex weighing (26-30 g) assigned into
      groups. Diabetes was induced by IP injection of alloxan monohydrate (150 mg/kg).
      The extracts (500 mg/kg) and standard (Glibenclamide 10 mg/kg) were administered
      to mice for 15 days. Serum biochemical parameters were monitored for the period
      of study. RESULTS: The leaves and bark extracts showed maximum alpha-glucosidase
      inhibition (96.61 +/- 2.13 and 93.58 +/- 2.31% respectively). The extracts
      treated and the standard treated groups showed significant decrease in the
      fasting blood glucose levels compared to diabetic control. The effect was more
      pronounced in mice treated with leaves extract. In the in vivo studies body
      weights of diabetic mice treated with Z. armatum extracts and the standard did
      not reduced to extent as observed in diabetic control and this difference was
      significant (p < 0.05). There was a significance (p < 0.001) improvement in blood
      hemoglobin, urea, creatinine, cholesterol, and triglycerides of the extracts
      treated diabetic mice. The extracts showed hypolipidemic effect by reducing the
      LDL level. The extracts produced no prominent changes in proteins levels.
      CONCLUSION: It can be concluded that Z. armatum extracts showed excellent
      antidiabetic potential in vivo and in vitro and could be considered for further
      appraisal in clinical assessment and drug development.

PMID- 29463308
TI  - Reproducibility of clinical research in critical care: a scoping review.
AB  - BACKGROUND: The ability to reproduce experiments is a defining principle of
      science. Reproducibility of clinical research has received relatively little
      scientific attention. However, it is important as it may inform clinical
      practice, research agendas, and the design of future studies. METHODS: We used
      scoping review methods to examine reproducibility within a cohort of randomized
      trials examining clinical critical care research and published in the top general
      medical and critical care journals. To identify relevant clinical practices, we
      searched the New England Journal of Medicine, The Lancet, and JAMA for randomized
      trials published up to April 2016. To identify a comprehensive set of studies for
      these practices, included articles informed secondary searches within other high
      impact medical and specialty journals. We included late-phase randomized
      controlled trials examining therapeutic clinical practices in adults admitted to
      general medical-surgical or specialty intensive care units (ICUs). Included
      articles were classified using a reproducibility framework. An original study was
      the first to evaluate a clinical practice. A reproduction attempt re-evaluated
      that practice in a new set of participants. RESULTS: Overall, 158 practices were
      examined in 275 included articles. A reproduction attempt was identified for 66
      practices (42%, 95% CI 33-50%). Original studies reported larger effects than
      reproduction attempts (primary endpoint, risk difference 16.0%, 95% CI 11.6-20.5%
      vs. 8.4%, 95% CI 6.0-10.8%, P = 0.003). More than half of clinical practices with
      a reproduction attempt demonstrated effects that were inconsistent with the
      original study (56%, 95% CI 42-68%), among which a large number were reported to
      be efficacious in the original study and to lack efficacy in the reproduction
      attempt (34%, 95% CI 19-52%). Two practices reported to be efficacious in the
      original study were found to be harmful in the reproduction attempt. CONCLUSIONS:
      A minority of critical care practices with research published in high-profile
      journals were evaluated for reproducibility; less than half had reproducible
      effects.

PMID- 29463310
TI  - The practice of intensive care in Latin America: a survey of academic
      intensivists.
AB  - BACKGROUND: Intensive care medicine is a relatively young discipline that has
      rapidly grown into a full-fledged medical subspecialty. Intensivists are
      responsible for managing an ever-increasing number of patients with complex, life
      threatening diseases. Several factors may influence their performance, including
      age, training, experience, workload, and socioeconomic context. The aim of this
      study was to examine individual- and work-related aspects of the Latin American
      intensivist workforce, mainly with academic appointments, which might influence
      the quality of care provided. In consequence, we conducted a cross-sectional
      study of intensivists at public and private academic and nonacademic Latin
      American intensive care units (ICUs) through a web-based electronic survey
      submitted by email. Questions about personal aspects, work-related topics, and
      general clinical workflow were incorporated. RESULTS: Our study comprised 735
      survey respondents (53% return rate) with the following country-specific
      breakdown: Brazil (29%); Argentina (19%); Chile (17%); Uruguay (12%); Ecuador
      (9%); Mexico (7%); Colombia (5%); and Bolivia, Peru, Guatemala, and Paraguay
      combined (2%). Latin American intensivists were predominantly male (68%) young
      adults (median age, 40 [IQR, 35-48] years) with a median clinical ICU experience
      of 10 (IQR, 5-20) years. The median weekly workload was 60 (IQR, 47-70) h. ICU
      formal training was between 2 and 4 years. Only 63% of academic ICUs performed
      multidisciplinary rounds. Most intensivists (85%) reported adequate conditions to
      manage patients with septic shock in their units. Unsatisfactory conditions were
      attributed to insufficient technology (11%), laboratory support (5%), imaging
      resources (5%), and drug shortages (5%). Seventy percent of intensivists
      participated in research, and 54% read scientific studies regularly, whereas 32%
      read no more than one scientific study per month. Research grants and
      pharmaceutical sponsorship are unusual funding sources in Latin America. Although
      Latin American intensivists are mostly unsatisfied with their income (81%), only
      a minority (27%) considered changing to another specialty before retirement.
      CONCLUSIONS: Latin American intensivists constitute a predominantly young adult
      workforce, mostly formally trained, have a high workload, and most are interested
      in research. They are under important limitations owing to resource constraints
      and overt dissatisfaction. Latin America may be representative of other world
      areas with similar challenges for intensivists. Specific initiatives aimed at
      addressing these situations need to be devised to improve the quality of critical
      care delivery in Latin America.

PMID- 29463311
TI  - Myeloid transformation of plasma cell myeloma: molecular evidence of clonal
      evolution revealed by next generation sequencing.
AB  - BACKGROUND: Plasma cell myeloma (PCM) is a neoplasm of terminally differentiated
      B lymphocytes with molecular heterogeneity. Although therapy-related myeloid
      neoplasms are common in plasma cell myeloma patients after chemotherapy,
      transdifferentiation of plasma cell myeloma into myeloid neoplasms has not been
      reported in literature. Here we report a very rare case of myeloid neoplasm
      transformed from plasma cell myeloma. CASE PRESENTATION: A 60-year-old man with a
      history of plasma cell myeloma with IGH-MAF gene rearrangement and RAS/RAF
      mutations developed multiple soft tissue lesions one year following melphalan
      based chemotherapy and autologous stem cell transplant. Morphological and
      immunohistochemical characterization of the extramedullary disease demonstrated
      that the tumor cells were derived from the monocyte-macrophage lineage. Next
      generation sequencing (NGS) studies detected similar clonal aberrations in the
      diagnostic plasma cell population and post-therapy neoplastic cells, including
      IGH-MAF rearrangement, multiple genetic mutations in RAS signaling pathway
      proteins, and loss of tumor suppressor genes. Molecular genetic analysis also
      revealed unique genomic alterations in the transformed tumor cells, including
      gain of NF1 and loss of TRAF3. CONCLUSION: To our knowledge, this is the first
      case of myeloid sarcoma transdifferentiated from plasma cell neoplasm. Our
      findings in this unique case suggest clonal evolution of plasma cell myeloma to
      myeloma neoplasm and the potential roles of abnormal RAS/RAF signaling pathway in
      lineage switch or transdifferentiation.

PMID- 29463312
TI  - SMS text messaging to measure working time: the design of a time use study among
      general practitioners.
AB  - BACKGROUND: Measuring the working hours of general practitioners (GPs) is an
      important but complex task due to the effects of bias related to self-reporting,
      recall, and stress. In this paper we describe the deployment, feasibility, and
      implementation of an innovative method for measuring, in real time, GPs' working
      time, plus the response to the study. METHODS: A Short Message Service (SMS)
      application was developed which sent messages at random to GPs during their
      working week. Approximately nineteen GPs participated each week during a period
      of 57 weeks. The text messages asked if GPs were doing activities related to
      patients, directly, indirectly, or not at all, at the moment of sending.
      Participants were requested to reply by SMS. RESULTS: Approximately 27,000
      messages were sent to 1051 GPs over more than one year. The SMS system was
      functioning 99.9% of the time. GPs replied to 94% of all the messages sent. Only
      a few participants dropped out of the study. The data was available in real time
      enabling the researchers to monitor the response and overall quality of the data
      each day. CONCLUSIONS: The SMS method offers advantages over other instruments of
      measurement because it allows a better response, ease of use and avoids recall
      bias. This makes it a feasible method to collect valid data about GPs working
      time.

PMID- 29463313
TI  - Lymphotoxin beta receptor-mediated NFkappaB signaling promotes glial lineage
      differentiation and inhibits neuronal lineage differentiation in mouse brain
      neural stem/progenitor cells.
AB  - BACKGROUND: Lymphotoxin (LT) is a lymphokine mainly expressed in lymphocytes.
      LTalpha binds one or two membrane-associated LTbeta to form LTalpha2beta1 or
      LTalpha1beta2 heterotrimers. The predominant LTalpha1beta2 binds to LTbeta
      receptor (LTbetaR) primarily expressed in epithelial and stromal cells. Most
      studies on LTbetaR signaling have focused on the organization, development, and
      maintenance of lymphoid tissues. However, the roles of LTbetaR signaling in the
      nervous system, particularly in neurogenesis, remain unknown. Here, we
      investigated the role of LTbetaR-mediated NFkappaB signaling in regulating neural
      lineage differentiation. METHODS: The C57BL/6J wild-type and GFAP-dnIkappaBalpha
      transgenic mice were used. Serum-free embryoid bodies were cultured from mouse
      embryonic stem cells and further induced into neural stem/progenitor cells
      (NSCs/NPCs). Primary neurospheres were cultured from embryonic and adult mouse
      brains followed by monolayer culture for amplification/passage. NFkappaB
      activation was determined by adenovirus-mediated NFkappaB-firefly-luciferase
      reporter assay and p65/RelB/p52 nuclear translocation assay. LTbetaR mRNA
      expression was evaluated by quantitative RT-PCR and LTbetaR protein expression
      was determined by immunohistochemistry and Western blot analysis. Multilabeled
      immunocytochemistry or immunohistochemistry followed by fluorescent confocal
      microscopy and quantitative analysis of neural lineage differentiation were
      performed. Graphing and statistical analysis were performed with GraphPad Prism
      software. RESULTS: In cultured NSCs/NPCs, LTalpha1beta2 stimulation induced an
      activation of classical and non-classical NFkappaB signaling. The expression of
      LTbetaR-like immunoreactivity in GFAP+/Sox2+ NSCs was identified in well
      established neurogenic zones of adult mouse brain. Quantitative RT-PCR and
      Western blot analysis validated the expression of LTbetaR in cultured NSCs/NPCs
      and brain neurogenic regions. LTbetaR expression was significantly increased
      during neural induction. LTalpha1beta2 stimulation in cultured NSCs/NPCs promoted
      astroglial and oligodendrocytic lineage differentiation, but inhibited neuronal
      lineage differentiation. Astroglial NFkappaB inactivation in GFAP-dnIkappaBalpha
      transgenic mice rescued LTbetaR-mediated abnormal phenotypes of cultured
      NSCs/NPCs. CONCLUSION: This study provides the first evidence for the expression
      and function of LTbetaR signaling in NSCs/NPCs. Activation of LTbetaR signaling
      promotes glial lineage differentiation. Our results suggest that neurogenesis is
      regulated by the adaptive immunity and inflammatory responses.

PMID- 29463314
TI  - Functional brain-specific microvessels from iPSC-derived human brain
      microvascular endothelial cells: the role of matrix composition on monolayer
      formation.
AB  - BACKGROUND: Transwell-based models of the blood-brain barrier (BBB) incorporating
      monolayers of human brain microvascular endothelial cells (dhBMECs) derived from
      induced pluripotent stem cells show many of the key features of the BBB,
      including expression of transporters and efflux pumps, expression of tight
      junction proteins, and physiological values of transendothelial electrical
      resistance. The fabrication of 3D BBB models using dhBMECs has so far been
      unsuccessful due to the poor adhesion and survival of these cells on matrix
      materials commonly used in tissue engineering. METHODS: To address this issue, we
      systematically screened a wide range of matrix materials (collagen I, hyaluronic
      acid, and fibrin), compositions (laminin/entactin), protein coatings
      (fibronectin, laminin, collagen IV, perlecan, and agrin), and soluble factors
      (ROCK inhibitor and cyclic adenosine monophosphate) in 2D culture to assess cell
      adhesion, spreading, and barrier function. RESULTS: Cell coverage increased with
      stiffness of collagen I gels coated with collagen IV and fibronectin. On 7 mg mL
      1 collagen I gels coated with basement membrane proteins (fibronectin, collagen
      IV, and laminin), cell coverage was high but did not reliably reach confluence.
      The transendothelial electrical resistance (TEER) on collagen I gels coated with
      basement membrane proteins was lower than on coated transwell membranes. Agrin, a
      heparin sulfate proteoglycan found in basement membranes of the brain, promoted
      monolayer formation but resulted in a significant decrease in transendothelial
      electrical resistance (TEER). However, the addition of ROCK inhibitor, cAMP, or
      cross-linking the gels to increase stiffness, resulted in a significant
      improvement of TEER values and enabled the formation of confluent monolayers.
      CONCLUSIONS: Having identified matrix compositions that promote monolayer
      formation and barrier function, we successfully fabricated dhBMEC microvessels in
      cross-linked collagen I gels coated with fibronectin and collagen IV, and treated
      with ROCK inhibitor and cAMP. We measured apparent permeability values for
      Lucifer yellow, comparable to values obtained in the transwell assay. During
      these experiments we observed no focal leaks, suggesting the formation of tight
      junctions that effectively block paracellular transport.

PMID- 29463315
TI  - X chromosome dosage and presence of SRY shape sex-specific differences in DNA
      methylation at an autosomal region in human cells.
AB  - BACKGROUND: Sexual dimorphism in DNA methylation levels is a recurrent epigenetic
      feature in different human cell types and has been implicated in predisposition
      to disease, such as psychiatric and autoimmune disorders. To elucidate the
      genetic origins of sex-specific DNA methylation, we examined DNA methylation
      levels in fibroblast cell lines and blood cells from individuals with different
      combinations of sex chromosome complements and sex phenotypes focusing on a
      single autosomal region--the differentially methylated region (DMR) in the
      promoter of the zona pellucida binding protein 2 (ZPBP2) as a reporter. RESULTS:
      Our data show that the presence of the sex determining region Y (SRY) was
      associated with lower methylation levels, whereas higher X chromosome dosage in
      the absence of SRY led to an increase in DNA methylation levels at the ZPBP2 DMR.
      We mapped the X-linked modifier of DNA methylation to the long arm of chromosome
      X (Xq13-q21) and tested the impact of mutations in the ATRX and RLIM genes,
      located in this region, on methylation levels. Neither ATRX nor RLIM mutations
      influenced ZPBP2 methylation in female carriers. CONCLUSIONS: We conclude that
      sex-specific methylation differences at the autosomal locus result from
      interaction between a Y-linked factor SRY and at least one X-linked factor that
      acts in a dose-dependent manner.

PMID- 29463316
TI  - Increased attachment security is related to early therapy drop-out in substance
      use disorders.
AB  - OBJECTIVES: Previous research work suggests a positive association between secure
      attachment and increased therapy adherence (TA) in different patient groups.
      However, there is still a strong need for research focusing on the influence of
      attachment on TA in substance use disorder (SUD) treatment. Hence, this study
      attempts to investigate the predictive value of different attachment patterns
      concerning TA in SUD inpatients. RESULTS: 122 (34 female) SUD inpatients
      completed the Attachment Style Questionnaire (ASQ) during the entry phase of
      therapeutic community treatment. After 6 weeks, subjects who remained in therapy
      (n = 47) completed the ASQ for a second time. In line with the literature,
      agglomerative Cluster Analysis suggested a two-cluster solution (Cluster I:
      increased secure attachment pattern; Cluster II: increased insecure attachment
      pattern). Notably, inpatients in Cluster I were more likely to drop out of
      treatment within the first 6 weeks (p < .001). Furthermore, subjects showed less
      "Confidence in Self and Others" (p < .05) after 6 weeks of treatment. Our
      findings indicate a negative predictive value of increased attachment security
      for TA in SUD inpatients. This finding probably mirrors a more realistic kind of
      self-assessment. More generally, the importance of considering attachment styles
      in SUD treatment is underlined.

PMID- 29463317
TI  - Adherence to the face-down positioning after vitrectomy and gas tamponade: a time
      series analysis.
AB  - OBJECTIVE: To determine the adherence to the face-down positioning (FDP) in 296
      patients who had undergone vitrectomy and gas tamponade. RESULTS: We studied 119
      female and 177 male patients who had undergone primary vitrectomy and gas
      tamponade for a macular hole (MH) or for rhegmatogenous retinal detachments
      (RRDs). Adherence was assessed and recorded four times per day for 3 days
      postsurgery. The mean +/- standard deviation adherence rate was 88.3 +/- 11.7
      (range 50.0-100.0). Female patients (90.8 +/- 10.0) had significantly better
      adherence than male patients (86.7 +/- 13.3; P < 0.02, U test). The adherence was
      significantly better after MH surgery (90.8 +/- 11.7) than after RRD surgery
      (87.5 +/- 12.5; P < 0.02). There were diurnal variations in adherence, being
      highest in the evening and significantly lower at midnight, and we evidenced a
      decline in adherence over time, with it being significantly low on the last
      follow-up day. Adherence to the FDP varied considerably among patients. Adherence
      was higher in female than in male patients, and higher in patients with MH than
      in those with RRD. We found patients age had no effect on adherence. Adherence
      also varied with time, being worst at midnight and declining over time.

PMID- 29463319
TI  - Performance of Arma chinensis reared on an artificial diet formulated using
      transcriptomic methods.
AB  - An artificial diet formulated for continuous rearing of the predator Arma
      chinensis was inferior to natural prey when evaluated using life history
      parameters. A transcriptome analysis identified differentially expressed genes in
      diet-fed and prey-fed A. chinensis that were suggestive of molecular mechanisms
      underlying the nutritive impact of the artificial diet. Changes in the diet
      formulation were made based on the transcriptome analysis and tested using life
      history parameters. The quantity of pig liver, chicken egg, tuna fish, biotin,
      nicotinamide, vitamin B6, thiamine, riboflavin, vitamin C, L-glutamine, and
      sucrose was reduced, and wheat germ oil, calcium pantothenate and folic acid were
      increased. Ecuadorian shrimp was added as a partial substitute for tuna fish.
      Several parameters improved over six generations, including increased egg
      viability, and decreased egg and adult cannibalism. Additionally, several
      parameters declined, including longer developmental times for 2nd-5th instars,
      and decreased nymphal weights. The improvements in life history parameters
      support the use of transcriptome analyses to help direct formulation
      improvements. However, the decline in some parameters suggests that additional
      information, e.g., proteomic data, may be useful as well to maximize diet
      formulations.

PMID- 29463318
TI  - New and emerging uses of CRISPR/Cas9 to genetically manipulate apicomplexan
      parasites.
AB  - Although the application of CRISPR/Cas9 genome engineering approaches was first
      reported in apicomplexan parasites only 3 years ago, this technology has rapidly
      become an essential component of research on apicomplexan parasites. This review
      briefly describes the history of CRISPR/Cas9 and the principles behind its use
      along with documenting its implementation in apicomplexan parasites, especially
      Plasmodium spp. and Toxoplasma gondii. We also discuss the recent use of
      CRISPR/Cas9 for whole genome screening of gene knockout mutants in T. gondii and
      highlight its use for seminal genetic manipulations of Cryptosporidium spp.
      Finally, we consider new variations of CRISPR/Cas9 that have yet to be
      implemented in apicomplexans. Whereas CRISPR/Cas9 has already accelerated rapid
      interrogation of gene function in apicomplexans, the full potential of this
      technology is yet to be realized as new variations and innovations are integrated
      into the field.

PMID- 29463320
TI  - Medialisation thyroplasty with tensor fascia lata: a novel approach for reducing
      post-thyroplasty complications.
AB  - BACKGROUND: Medialisation thyroplasty is considered the 'gold standard' treatment
      for unilateral vocal fold paralysis, enabling improvement of voice and swallowing
      function, and preventing life-threatening aspiration events. The most commonly
      used laryngeal implants induce some degree of local tissue inflammatory response,
      and carry the risk of immediate or delayed implant extrusion. METHODS: This paper
      describes a novel approach for medialisation thyroplasty. Specifically, it
      utilises a ribbon of autologous tensor fascia lata harvested at the time of
      surgery. This is layered within the paraglottic space in a manner similar to Gore
      Tex thyroplasty. RESULTS: Thus far, this method has been accomplished in two
      patients with unilateral vocal fold paralysis, who also received prior
      radiotherapy to the head and neck. CONCLUSION: Given the increased risk of post
      operative wound breakdown and infection in irradiated patients, it is suggested
      that this new approach will lead to improved outcomes, and a decrease in
      complications such as extrusion or wound infection, particularly in this patient
      population.

PMID- 29463321
TI  - Olive cultivar and maturation process on the oviposition preference of Bactrocera
      oleae (Rossi) (Diptera: Tephritidae).
AB  - The olive fly, Bactrocera oleae (Rossi) (Diptera: Tephritidae), is a key-pest in
      the main olives producing areas worldwide, and displays distinct preference to
      different olive cultivars. The present work intended to study oviposition
      preference towards three Portuguese cultivars (Cobrancosa, Madural, and Verdeal
      Transmontana) at different maturation indexes. Multiple oviposition bioassays
      (multiple-choice and no-choice) were conducted to assess cultivar preference. No
      choice bioassays were conducted to assess the influence of different maturation
      indexes (MI 2; MI 3, and MI 4) in single cultivars. The longevity of olive fly
      adults according to the cultivar in which its larvae developed was also evaluated
      through survival assays. Cultivar and maturation are crucial aspects in olive fly
      preference. Field and laboratory assays revealed a preference towards cv. Verdeal
      Transmontana olives and a lower susceptibility to cv. Cobrancosa olives. A higher
      preference was observed for olives at MI 2 and MI 3. The slower maturation
      process in cv. Verdeal Transmontana (still green while the other cultivars are
      reddish or at black stage) seems to have an attractive effect on olive fly
      females, thus increasing its infestation levels. Olive fly adults from both sexes
      live longer if emerged from pupae developed from cv. Verdeal Transmontana fruits
      and live less if emerged from cv. Cobrancosa. Therefore, olive cultivar and
      maturation process are crucial aspects in olive fly preference, also influencing
      the longevity of adults.

PMID- 29463322
TI  - Factors influencing microhabitat selection and food preference of tree-dwelling
      earwigs (Dermaptera) in a temperate floodplain forest.
AB  - The ecology of earwigs in natural forest ecosystems is poorly understood. We used
      sweeping to determine the population densities of adult earwigs, by sex and
      species, on ten tree species in a temperate floodplain forest in southern Moravia
      (Czech Republic). We also determined the relationships between the properties of
      tree species and earwig density and diet as indicated by digestive tract
      contents. The densities and diet composition of earwigs differed between the
      three detected earwig species [Apterygida media (Hagenbach, 1822), Chelidurella
      acanthopygia (Gene, 1832) and Forficula auricularia Linnaeus, 1758] and among
      tree species. Earwig densities were related to lichen coverage and fungal
      coverage on the trees. The diet of earwigs was associated with specific leaf
      area, herbivore damage to the leaves, and light exposure of the trees. A. media
      was the most abundant of the three earwig species. Although the contents of its
      digestive tract changed depending on available food resources, A. media appeared
      to preferentially consume soft-bodied insect herbivores and fungi associated with
      wounds caused by herbivores rather than plant material. Therefore, this species
      has the potential to help reduce the population densities of soft-bodied pests of
      forest trees.

PMID- 29463323
TI  - Innate immunity and environmental correlates of Haemoproteus prevalence and
      intensity in an opportunistic breeder.
AB  - While parasite infection can have substantial fitness consequences in organisms,
      the predictors of parasite prevalence and intensity are often complex and vary
      depending on the host species. Here, we examined correlates of Haemoproteus (a
      common malaria parasite) prevalence and intensity in an opportunistically
      breeding songbird, the red crossbill (Loxia curvirostra). Specifically, we
      quantified Haemoproteus prevalence and intensity in crossbills caught in the
      Grand Teton National Park from 2010 to 2013. We found that parasite prevalence
      varies seasonally and across years, with the highest number of infected
      individuals occurring in the summer, although there was variation across summers
      sampled, and that prevalence was positively related to annual mean cone crop
      sizes (a measure of crossbill food abundance) and daily ambient temperature (a
      correlate of vector abundance). Parasite intensity was significantly and
      positively related to one measure of innate immunity, leucocyte counts per blood
      volume. Finally, neither crossbill age, ecomorph, nor sex had significant effects
      on parasite infection intensity; however, parasite prevalence did significantly
      vary among ecomorph and age classes. These results support the interpretation
      that a combination of physiological (specifically immune activity) and
      environmental factors affects parasite prevalence and infection intensity in this
      opportunistically breeding avian species.

PMID- 29463324
TI  - Functions of Turkish evidentials in early child-caregiver interactions: a growth
      curve analysis of longitudinal data.
AB  - In languages with evidential marking, utterances consist of an informational
      content and a specification of the mode of access to that information. In this
      first longitudinal study investigating the acquisition of the Turkish evidential
      marker -mIs in naturalistic child-caregiver interactions, we examined six
      children between 8 and 36 months of age. We charted individual differences in
      child and caregiver speech over time by conducting growth curve analyses.
      Children followed a similar course of acquisition in terms of the proportion of
      the marker in overall speech. However, children exhibited differences with
      respect to the order of emergence of different evidential functions (e.g.,
      inference, hearsay), where each child showed a unique pattern irrespective of the
      frequency in caregiver input. Nonfactual use of the marker was very frequent in
      child and caregiver speech, where high-SES caregivers mostly produced the marker
      during story-telling and pretend play, and low-SES caregivers for regulating the
      child's behavior.

PMID- 29463325
TI  - Paediatric obstructive sleep apnoea: is our operative management evidence-based?
AB  - BACKGROUND: Despite the plethora of publications on the subject of paediatric
      obstructive sleep apnoea, there seems to be wide variability in the literature
      and in practice, regarding recourse to surgery, the operation chosen, the
      benefits gained and post-operative management. This may reflect a lack of high
      level evidence. METHODS: A systematic review of four significant controversies in
      paediatric ENT was conducted from the available literature: tonsillectomy versus
      tonsillotomy, focusing on the evidence base for each; anaesthetic considerations
      in paediatric obstructive sleep apnoea surgery; the objective evidence for the
      benefits of surgical treatment for obstructive sleep apnoea; and the medical
      treatment options for residual obstructive sleep apnoea after surgical treatment.
      RESULTS AND CONCLUSION: There are many gaps in the evidence base for the surgical
      correction of obstructive sleep apnoea. There is emerging evidence favouring
      subtotal tonsillectomy. There is continuing uncertainty around the prediction of
      the level of post-operative care that any individual child might require. The
      long-term benefit of surgical correction is a particularly fertile ground for
      further research.

PMID- 29463326
TI  - Functional characteristics of chemosensory proteins in the sawyer beetle
      Monochamus alternatus Hope.
AB  - The Japanese pine sawyer, Monochamus alternatus Hope (Coleoptera: Cerambycidae),
      is a major pest of pines and it is also the key vector of the exotic pinewood
      nematode in China. In the present study, we cloned, expressed, and purified a
      chemosensory protein (CSP) in M. alternatus. We surveyed its expression in
      various developmental stages of male and female adult tissues and determined its
      binding affinities for different pine volatiles using a competitive binding
      fluorescence assay. A CSP known as CSP5 in M. alternatus was obtained from an
      antennal cDNA library and expressed in Escherichia coli. Quantitative reverse
      transcription polymerase chain reaction results indicated that the CSP5 gene was
      mainly expressed in male and female antennae. Competitive binding assays were
      performed to test the binding affinity of recombinant CSP5 to 13 odour molecules
      of pine volatiles. The results showed that CSP5 showed very strong binding
      abilities to myrcene, (+)-beta-pinene, and (-)-isolongifolene, whereas the
      volatiles 2-methoxy-4-vinylphenol, p-cymene, and (+)-limonene oxide have
      relatively weak binding affinity at pH 5.0. Three volatiles myrcene, (+)-beta
      pinene, and (-)-isolongifolene may play crucial roles in CSP5 binding with
      ligands but this needs further study for confirmation. The sensitivity of insect
      to host plant volatiles can effectively be used to control and monitor the
      population through mass trapping as part of integrated pest management programs.

PMID- 29463327
TI  - Past trauma and future choices: differences in discounting in low-income, urban
      African Americans.
AB  - BACKGROUND: Exposure to traumatic events is surprisingly common, yet little is
      known about its effect on decision making beyond the fact that those with post
      traumatic stress disorder are more likely to have substance-abuse problems. We
      examined the effects of exposure to severe trauma on decision making in low
      income, urban African Americans, a group especially likely to have had such
      traumatic experiences. METHOD: Participants completed three decision-making tasks
      that assessed the subjective value of delayed monetary rewards and payments and
      of probabilistic rewards. Trauma-exposed cases and controls were propensity
      matched on demographic measures, treatment for psychological problems, and
      substance dependence. RESULTS: Trauma-exposed cases discounted the value of
      delayed rewards and delayed payments, but not probabilistic rewards, more steeply
      than controls. Surprisingly, given previous findings that suggested women are
      more affected by trauma when female and male participants' data were analyzed
      separately, only the male cases showed steeper delay discounting. Compared with
      nonalcoholic males who were not exposed to trauma, both severe trauma and alcohol
      dependence produced significantly steeper discounting of delayed rewards.
      CONCLUSIONS: The current study shows that exposure to severe trauma selectively
      affects fundamental decision-making processes. Only males were affected, and
      effects were observed only on discounting delayed outcomes (i.e. intertemporal
      choice) and not on discounting probabilistic outcomes (i.e. risky choice). These
      findings are the first to show significant differences in the effects of trauma
      on men's and women's decision making, and the selectivity of these effects has
      potentially important implications for treatment and also provides clues as to
      underlying mechanisms.

PMID- 29463328
TI  - Bilateral sudden sensorineural hearing loss as a first symptom of infective
      endocarditis: two case reports.
AB  - BACKGROUND: Septic emboli are an unusual cause of sudden sensorineural hearing
      loss, for which few reports exist in the literature. CASE REPORT: This paper
      presents two cases of sudden sensorineural hearing loss, initially considered as
      idiopathic, but which were caused by septic emboli. Hearing loss in these cases
      was bilateral, sequential and total. The first patient had mild fever one week
      prior to their presentation with sudden sensorineural hearing loss; the other
      patient had no additional symptoms at presentation. These patients were later
      diagnosed with infective endocarditis, at two and seven months following the
      sudden sensorineural hearing loss respectively, showing that septic emboli had
      been the cause of sudden sensorineural hearing loss. CONCLUSION: Septic emboli
      should be considered as a possible cause of sudden sensorineural hearing loss in
      cases of total hearing loss. This form of hearing loss should prompt the
      otolaryngologist to further investigate for infective endocarditis.

PMID- 29463329
TI  - Indirect visualisation of the upper pole during tonsillectomy.
AB  - BACKGROUND: During tonsillectomy, one of the key concerns is establishing
      adequate haemostasis. Intra-operative haemorrhage from the upper pole of the
      tonsil fossae can be a challenge to deal with because of an inability to clearly
      visualise bleeding points. Laryngeal mirrors are readily available in an ENT
      operating theatre and routinely used for indirect visualisation of the post-nasal
      space during adenoidectomy. OBJECTIVE: This paper describes a technique,
      utilising a laryngeal mirror placed within the tonsil fossa (after having removed
      the palatine tonsil), to visualise the upper pole and any bleeding points.
      RESULTS AND CONCLUSION: Laryngeal mirrors can be used with case to inspect the
      tonsil fossa post-tonsillectomy for bleeding points which may not be directly
      visible, so that these can be cauterised.

PMID- 29463330
TI  - A Chemical-Biological-Radio-Nuclear (CBRN) Filter can be Added to the Air-Outflow
      Port of a Ventilator to Protect a Home Ventilated Patient From Inhalation of
      Toxic Industrial Compounds.
AB  - OBJECTIVES: Chemical-biological-radio-nuclear (CBRN) gas masks are the standard
      means for protecting the general population from inhalation of toxic industrial
      compounds (TICs), for example after industrial accidents or terrorist attacks.
      However, such gas masks would not protect patients on home mechanical
      ventilation, as ventilator airflow would bypass the CBRN filter. We therefore
      evaluated in vivo the safety of adding a standard-issue CBRN filter to the air
      outflow port of a home ventilator, as a method for providing TIC protection to
      such patients. METHODS: Eight adult patients were included in the study. All had
      been on stable, chronic ventilation via a tracheostomy for at least 3 months
      before the study. Each patient was ventilated for a period of 1 hour with a
      standard-issue CBRN filter canister attached to the air-outflow port of their
      ventilator. Physiological and airflow measurements were made before, during, and
      after using the filter, and the patients reported their subjective sensation of
      ventilation continuously during the trial. RESULTS: For all patients, and
      throughout the entire study, no deterioration in any of the measured
      physiological parameters and no changes in measured airflow parameters were
      detected. All patients felt no subjective difference in the sensation of
      ventilation with the CBRN filter canister in situ, as compared with ventilation
      without it. This was true even for those patients who were breathing
      spontaneously and thus activating the ventilator's trigger/sensitivity function.
      No technical malfunctions of the ventilators occurred after addition of the CBRN
      filter canister to the air-outflow ports of the ventilators. CONCLUSIONS: A CBRN
      filter canister can be added to the air-outflow port of chronically ventilated
      patients, without causing an objective or subjective deterioration in the quality
      of the patients' mechanical ventilation. (Disaster Med Public Health
      Preparedness. 2018;page 1 of 5).

PMID- 29463331
TI  - Rethinking the Molecular Diagnostics for Methicillin-Resistant Staphylococcus
      aureus.

PMID- 29463332
TI  - Consumption of sugar-sweetened and artificially sweetened soft drinks and risk of
      obesity-related cancers.
AB  - OBJECTIVE: To test the hypothesis that more frequent consumption of sugar
      sweetened soft drinks would be associated with increased risk of obesity-related
      cancers. Associations for artificially sweetened soft drinks were assessed for
      comparison. DESIGN: Prospective cohort study with cancers identified by linkage
      to cancer registries. At baseline, participants completed a 121-item FFQ
      including separate questions about the number of times in the past year they had
      consumed sugar-sweetened or artificially sweetened soft drinks. Anthropometric
      measurements, including waist circumference, were taken and questions about
      smoking, leisure-time physical activity and intake of alcoholic beverages were
      completed. SETTING: The Melbourne Collaborative Cohort Study (MCCS) is a
      prospective cohort study which recruited 41 514 men and women aged 40-69 years
      between 1990 and 1994. A second wave of data collection occurred in 2003-2007.
      SUBJECTS: Data for 35 593 participants who developed 3283 incident obesity
      related cancers were included in the main analysis. RESULTS: Increasing frequency
      of consumption of both sugar-sweetened and artificially sweetened soft drinks was
      associated with greater waist circumference at baseline. For sugar-sweetened soft
      drinks, the hazard ratio (HR) for obesity-related cancers increased as frequency
      of consumption increased (HR for consumption >1/d v. 1/d v. <1/month=1.00; 95 %
      CI 0.79, 1.27; P-trend=0.61). CONCLUSIONS: Our results add to the justification
      to minimise intake of sugar-sweetened soft drinks.

PMID- 29463333
TI  - Why policy needs history (and historians).
AB  - Policy makers like the idea of new initiatives and fresh starts, unencumbered by,
      even actively overthrowing, what has been done in the past. At the same time,
      history can be pigeonholed as fusty and antiquarian, dealing with long past
      events of no relevance to the present. Academic historians are sometimes bound up
      in their own worlds. The debates central to academe may have little direct
      relevance to the immediate concerns of policy making. The paper argues that
      history, as the evidence-based discipline par excellence, is as relevant as other
      approaches to evidence-based policy making. Case studies can show us the nature
      of that relevance. How to achieve influence for history also needs discussion.
      The relationship is not straightforward and will vary according to time and
      place. History is an interpretative discipline, not just a collection of 'facts'.
      The paper discusses how historians work and why it is important for policy makers
      to engage, not just with history, but with historians as well. Historians too
      need to think about the value of bringing their analysis into policy.

PMID- 29463334
TI  - The Role of Oral Health in Complex Emergencies and Disaster Rehabilitation
      Medicine.
AB  - This paper presents an overview of the importance of oral health in complex
      emergencies. It highlights the importance of maintaining general and oral health
      in the acute, intermediate and long-term phases of such events which are
      increasing in frequency. The importance of oral health as an early warning sign
      for systemic disease and deprivation is also explored along with the crucial role
      of oral health in maintaining quality of life through adequate nutrition and
      speech. The overview of oral health in these situations identifies the need for
      training dental personnel as members of rehabilitation teams that set out to
      manage these disasters. They can quickly help in improving quality of life for
      victims by extracting carious and painful teeth as necessary, and also form part
      of an oral health education program for aid agencies. They can also be the first
      to identify systemic diseases like HIV and may also play a role in identifying
      victims of abuse, as non-accidental injuries can frequently present in the oro
      facial region. The oral health overview concludes by describing the contents of
      innovative oral health packs that are tailored to prevention of dental diseases
      and that can be readily incorporated as part of food packs distributed by aid
      agencies. (Disaster Med Public Health Prepardness. 2018;page 1 of 6).

PMID- 29463335
TI  - Safety of Palivizumab Stewardship in Conjunction with Infection Prevention and
      Control Strategies for Healthcare-Associated Respiratory Syncytial Virus
      Infections.
AB  - Transitioning from administration of monthly palivizumab to a single dose at
      discharge was associated with substantial pharmacy cost savings. With the
      concurrent adoption of private hospital rooms and visitor restriction policies,
      hospital-wide and neonatal intensive care unit healthcare-associated respiratory
      syncytial virus infections decreased following these changes. Infect Control Hosp
      Epidemiol 2018;39:485-487.

PMID- 29463336
TI  - Epidemiology of viral respiratory infections in Australian working-age adults (20
      64 years): 2010-2013.
AB  - Acute respiratory infections cause significant morbidity and mortality accounting
      for 5.8 million deaths worldwide. In Australia, influenza-like illness (ILI),
      defined as cough, fever and fatigue is a common presentation in general practice
      and results in reduced productivity and lost working days. Little is known about
      the epidemiology of ILI in working-age adults. Using data from the ASPREN
      influenza surveillance network in Australia (2010-2013) we found that working-age
      adults made up 45.2% of all ILI notifications with 55% of samples positive for at
      least one respiratory virus. Viruses most commonly detected in our study included
      influenza A (20.6%), rhinovirus (18.6%), influenza B (6.2%), human meta
      pneumovirus (3.4%), respiratory syncytial virus (3.1%), para-influenza virus
      (2.6%) and adenovirus (1.3%). We also demonstrated that influenza A is the
      predominant virus that increases ILI (by 1.2% per month for every positive
      influenza A case) in working-age adults during autumn-winter months while other
      viruses are active throughout the year. Understanding the epidemiology of viral
      respiratory infections through a year will help clinicians make informed
      decisions about testing, antibiotic and antiviral prescribing and when the
      beginning of the 'flu season' can be more confidently predicted.

PMID- 29463337
TI  - When regularization gets it wrong: children over-simplify language input only in
      production.
AB  - Children tend to regularize their productions when exposed to artificial
      languages, an advantageous response to unpredictable variation. But
      generalizations in natural languages are typically conditioned by factors that
      children ultimately learn. In two experiments, adult and six-year-old learners
      witnessed two novel classifiers, probabilistically conditioned by semantics.
      Whereas adults displayed high accuracy in their productions - applying the
      semantic criteria to familiar and novel items - children were oblivious to the
      semantic conditioning. Instead, children regularized their productions, over
      relying on only one classifier. However, in a two-alternative forced-choice task,
      children's performance revealed greater respect for the system's complexity: they
      selected both classifiers equally, without bias toward one or the other, and
      displayed better accuracy on familiar items. Given that natural languages are
      conditioned by multiple factors that children successfully learn, we suggest that
      their tendency to simplify in production stems from retrieval difficulty when a
      complex system has not yet been fully learned.

PMID- 29463338
TI  - A Novel Treatment Protocol (Nocebo Hypothesis Cognitive Behavioural Therapy; NH
      CBT) for Functional Neurological Symptom Disorder/Conversion Disorder: A
      Retrospective Consecutive Case Series.
AB  - BACKGROUND: Theories concerning the aetiology of functional neurological symptom
      disorder (FNSD; also known as conversion disorder) have historically inferred
      that psychological factors or dissociative states underlie patients' symptoms.
      Current psychological models of functional neurological symptoms suggest that
      some type of 'top-down' representations/beliefs are activated automatically
      (without conscious awareness), leading to symptoms. It is assumed that these
      representations or beliefs are similar to the idea 'I am neurologically damaged',
      as in our clinical experience, almost all patients have some reason to doubt the
      integrity of their neurological system. AIMS: It was hypothesized that FNSD
      arises from a belief of being neurologically damaged (via a mechanism akin to a
      nocebo response), and an interdisciplinary treatment protocol was developed
      consistent with this hypothesis, transparently sharing this theory with
      participants. METHOD: A retrospective consecutive case series design was
      utilized, measuring functional independence and symptom remission. RESULTS: Of
      the 13 episodes of care, 12 resulted in complete or almost complete symptom
      remission. Length of stay in rehabilitation was also reduced compared with
      previous treatment attempts. CONCLUSIONS: It appears as if the treatment protocol
      may be very effective, and further controlled study appears warranted.

PMID- 29463340
TI  - Evaluation of a Novel Disaster Nursing Education Method.
AB  - OBJECTIVE: A common method of disaster training is needed to improve disaster
      nursing education and facilitate better communication among interprofessional
      disaster responders. To inform the development of disaster nursing curricula, a
      novel disaster nursing education method consistent with Homeland Security
      Exercise and Evaluation Program (HSEEP) and the International Council of Nurses
      (ICN) framework was developed to improve disaster nursing competencies in a
      baccalaureate nursing program. METHODS: In total, 89 undergraduate nursing
      students participated. Perceived disaster nursing knowledge, confidence, and
      training/response were assessed with 14 items before and after the education.
      RESULTS: Exploratory factor analysis showed 3 factors, knowledge, confidence, and
      training/response, explained 71% of variation in items. Nursing students showed
      large improvements in perceived disaster nursing knowledge (t=11.95, P<0.001,
      Cohen's d=1.76), moderate increases in perceived confidence (t=4.54, P<0.001,
      d=0.67), and no change in disaster training and response (t=0.94, P=0.351,
      d=0.13). CONCLUSIONS: Results show preliminary evidence supporting the
      effectiveness of disaster nursing education informed by HSEEP. This training has
      the potential to fill current practice gaps in disaster nursing knowledge and
      build confidence to use those skills in practice. (Disaster Med Public Health
      Preparedness. 2018;page 1 of 8).

PMID- 29463339
TI  - Cost-Effectiveness of Competing Treatment Strategies for Clostridium difficile
      Infection: A Systematic Review.
AB  - BACKGROUND Clostridium difficile infection (CDI) presents a substantial economic
      burden and is associated with significant morbidity. While multiple treatment
      strategies have been evaluated, a cost-effective management strategy remains
      unclear. OBJECTIVE We conducted a systematic review to assess cost-effectiveness
      analyses of CDI treatment and to summarize key issues for clinicians and policy
      makers to consider. METHODS We searched PubMed and 5 other databases from
      inception to August 2016. These searches were not limited by study design or
      language of publication. Two reviewers independently screened the literature,
      abstracted data, and assessed methodological quality using the Drummond and
      Jefferson checklist. We extracted data on study characteristics, type of CDI,
      treatment characteristics, and model structure and inputs. RESULTS We included 14
      studies, and 13 of these were from high-income countries. More than 90% of these
      studies were deemed moderate-to-high or high quality. Overall, 6 studies used a
      decision-tree model and 7 studies used a Markov model. Cost of therapy, time
      horizon, treatment cure rates, and recurrence rates were common influential
      factors in the study results. For initial CDI, fidaxomicin was a more cost
      effective therapy than metronidazole or vancomycin in 2 of 3 studies. For severe
      initial CDI, 2 of 3 studies found fidaxomicin to be the most cost-effective
      therapy. For recurrent CDI, fidaxomicin was cost-effective in 3 of 5 studies,
      while fecal microbiota transplantation (FMT) by colonoscopy was consistently cost
      effective in 4 of 4 studies. CONCLUSIONS The cost-effectiveness of fidaxomicin
      compared with other pharmacologic therapies was not definitive for either initial
      or recurrent CDI. Despite its high cost, FMT by colonoscopy may be a cost
      effective therapy for recurrent CDI. A consensus on model design and assumptions
      are necessary for future comparison of CDI treatment. Infect Control Hosp
      Epidemiol 2018;39:412-424.

PMID- 29463341
TI  - Human visceral leishmaniasis: factors associated with deaths in Belo Horizonte,
      Minas Gerais state, Brazil from 2006 to 2013.
AB  - The aim of this study was to evaluate the distribution of cases and the social
      determinants associated with death from human visceral leishmaniasis (HVL) and VL
      HIV co-infection in Belo Horizonte, Minas Gerais state, Brazil, between 2006 and
      2013. Descriptive statistics and analysis of associations were performed using
      chi-square of the raised variables, such as sex, age, skin colour and schooling
      of cases of HVL. During the study period, there were 866 cases of HVL with 111
      deaths in Belo Horizonte. Morbidity and lethality rates (LR) of HVL in Belo
      Horizonte remained high over almost all the years evaluated, with an average
      incidence rate of 4.18 cases/100 000 inhabitants and a LR of 11.16%. With respect
      to skin colour, it was found that people characterised as black or mulatto had
      higher morbidity, followed by white. Regarding schooling, LR was more prevalent
      among individuals with lower education. One of the social risk factors was co
      infection with HIV, which was present in many cases of HVL. Furthermore, it was
      found that older age and the male sex were also risk factors for death from HVL
      in Belo Horizonte.

PMID- 29463342
TI  - Segmental superficial parotidectomy in the surgical treatment of benign parotid
      tumours.
AB  - OBJECTIVE: To evaluate the efficacy and safety of segmental superficial
      parotidectomy in the surgical treatment of benign parotid tumours. METHODS:
      Patients who underwent parotidectomy for benign primary parotid tumours limited
      to the superficial lobe were retrospectively reviewed. Tumour location, size,
      surgical procedure, follow-up period, complications and recurrence rates were
      noted. RESULTS: The study included a total of 39 patients: 22 underwent segmental
      superficial parotidectomy (group 1) and 17 underwent superficial parotidectomy
      (group 2). The mean follow-up period was 41.79 months (range, 13-85 months).
      There were no recurrences in either group during the follow-up period. No
      significant differences were found between the two groups in terms of tumour
      size, complications or recurrence rates. CONCLUSION: Segmental superficial
      parotidectomy is a safe and effective option in the surgical treatment of benign
      parotid tumours.

PMID- 29463343
TI  - Characteristics associated with mortality in patients with chronic obstructive
      pulmonary disease (COPD)-heart failure coexistence.
AB  - : Aim To investigate if cardiac/pulmonary functional tests and variables obtained
      from clinical practice (body mass index, dyspnea, functional class, clinical
      judgment of disability to perform an exercise test and previous hospitalization
      rate) are related to mortality in patients with overlap chronic obstructive
      pulmonary disease (COPD) and chronic heart failure (CHF). BACKGROUND: Although
      the coexistence of COPD and CHF has been growingly reported, description of
      survival predictors considering the presence of both conditions is still scarce.
      METHODS: Using a cohort design, outpatients with the previous diagnosis of COPD
      and/or CHF that performed both spirometry and echocardiography in the same year
      were followed-up during a mean of 20.9+/-8.5 months. Findings Of the 550 patients
      initially evaluated, 301 had both spirometry and echocardiography: 160 (53%) with
      COPD on isolation; 100 (33%) with CHF on isolation; and 41 (14%) with overlap.
      All groups presented similar mortality: COPD 17/160 (11%); CHF 12/100 (12%); and
      overlap 7/41 (17%) (P=0.73). In the overlap group (n=41), inability to exercise
      and hospitalization rate were the unique parameters associated with higher
      mortality (seven events) in univariate analyses. In conclusion, inability to
      exercise and hospitalization rate emerged as the unique parameters associated
      with mortality in our sample.

PMID- 29463344
TI  - Haemodynamic consequences following closure of an Abernethy malformation in a
      patient following a total cavopulmonary shunt.
AB  - A 17-year-old girl with situs ambiguous, hypoplastic right ventricle with a large
      ventricular septal defect, and severe pulmonary stenosis had undergone Kawashima
      operation 10 years back. She had significant desaturation because of a large
      Abernethy malformation, with reverse shunting from the inferior caval vein to the
      portal vein. It was closed with a vascular plug, with improvement in oxygen
      saturation. She developed extensive inferior caval vein thrombus following the
      procedure, which was managed conservatively by anti-coagulation.

PMID- 29463345
TI  - 21st Century Cognitive Behavioural Therapy for Anger: A Systematic Review of
      Research Design, Methodology and Outcome.
AB  - BACKGROUND: Past reviews of cognitive behavioural therapy (CBT) for anger have
      focused on outcome in specific subpopulations, with few questions posed about
      research design and methodology. Since the turn of the century, there has been a
      surge of methodologically varied studies awaiting systematic review. AIMS: The
      basic aim was to review this recent literature in terms of trends and patterns in
      research design, operationalization of anger, and covariates such as social
      desirability bias (SDB). Also of interest was clinical outcome. METHOD: After
      successive culling, 42 relevant studies were retained. These were subjected to a
      rapid evidence assessment (REA) with special attention to design (ranked on the
      Scientific Methods Scale) measurement methodology (self-monitored behaviour,
      anger questionnaires, and others' ratings), SDB assessment, and statistical
      versus clinical significance. RESULTS: The randomized controlled trial
      characterized 60% of the studies, and the State Trait Anger Expression Inventory
      was the dominant measure of anger. All but one of the studies reported
      statistically significant outcome, and all but one of the 21 studies evaluating
      clinical significance laid claim to it. The one study with neither statistical
      nor clinical significance was the only one that had assessed and corrected for
      SDB. CONCLUSIONS: Measures remain relatively narrow in scope, but study designs
      have improved, and the outcomes suggest efficacy and clinical effectiveness. In
      conjunction with previous findings of an inverse relationship between anger and
      SDB, the results raise the possibility that the favourable picture of CBT for
      anger may need closer scrutiny with SDB and other methodological details in mind.

PMID- 29463346
TI  - Pathogenicity and genetic characterisation of a novel reassortant, highly
      pathogenic avian influenza (HPAI) H5N6 virus isolated in Korea, 2017.
AB  - We investigated influenza A(H5N6) viruses from migratory birds in Chungnam and
      Gyeonggi Provinces, South Korea following a reported die-off of poultry in nearby
      provinces in November 2017. Genetic analysis and virulence studies in chickens
      and ducks identified our isolate from December 2017 as a novel highly pathogenic
      avian influenza virus. It resulted from reassortment between the highly virulent
      H5N8 strain from Korea with the N6 gene from a low-pathogenic H3N6 virus from the
      Netherlands.

PMID- 29463347
TI  - Deciphering the Spectrum of Mitochondrial DNA Mutations in Hepatocellular
      Carcinoma Using High-Throughput Sequencing.
AB  - Accumulation of mitochondrial DNA (mtDNA) mutations has been proposed to
      contribute to the initiation and progression of tumors. By using high-throughput
      sequencing strategies, we measured 33 specimens including 11 hepatocellular
      carcinoma (HCC) tissues, 11 corresponding adjacent tissues, and 11 normal liver
      tissues. We identified 194 single nucleotide variants (SNVs; including insert and
      deletion) in 33 liver tissues, and 13 somatic novel mutations were detected,
      including 7 mutations in the coding region. One of the seven somatic mutations
      (T7609C, 91.09%) is synonymous, which does not change amino acid coding; the
      other four somatic mutations (T6115C, 65.74%; G8387A, 12.23%; G13121A, 93.08%;
      and T14180C, 28.22%) could result in amino acid substitutions, potentially
      leading to mitochondrial dysfunction. Furthermore, two mutations in tRNA might
      influence amino acid transportation. Consistent with a previous study, we also
      found that mtDNA copy number was significantly reduced in HCC tissues. Therefore,
      we established a mitochondrial genome depletion cell line rho0 and revealed that
      mtDNA loss reduced proliferation and migration in HCC cells but promoted their
      resistance to 5-fluorouracil. Our results suggested that somatic mtDNA mutations
      may cause mitochondrial dysfunction and affect chemoresistance of HCC cells.
      These new identified somatic mutations may serve as a reference for future
      studies of cancer mitochondrial genomes.

PMID- 29463350
TI  - Flight.

PMID- 29463348
TI  - Long Noncoding RNA FGFR3-AS1 Promotes Hepatocellular Carcinoma Carcinogenesis via
      Modulating the PI3K/AKT Pathway.
AB  - Hepatocellular carcinoma (HCC) as one of the most refractory cancers leads to
      high mortality worldwide. Long noncoding RNAs have been widely acknowledged as
      important biomarkers and therapeutic targets in HCC. In this study, we
      investigated the effects of long noncoding RNA FGFR3-AS1 on tumor growth and
      metastasis in HCC. First, we found that the expression of FGFR3-AS1 was
      upregulated about threefold in HCC samples and cell lines. We knocked down FGFR3
      AS1 in Huh7 and Hep3B cells and found that FGFR3-AS1 knockdown significantly
      inhibited cell proliferation but induced apoptosis. Moreover, FGFR3-AS1 knockdown
      led to more HCC cells arrested in the G0 stage. FGFR3-AS1 knockdown significantly
      inhibited cell migration and invasion. Additionally, we found that FGFR3-AS1
      silencing dramatically delayed tumor growth in vivo. We found that,
      mechanistically, FGFR3-AS1 silencing decreased the activation of the PI3K/AKT
      signaling pathway. Taken together, our data demonstrated the pro-oncogenic role
      of FGFR3-AS1 in HCC and suggested that FGFR3-AS1 may serve as a novel biomarker
      for the diagnosis and therapeutic target for HCC treatment.

PMID- 29463351
TI  - Risk Factors for Hearing Decrement Among U.S. Air Force Aviation-Related
      Personnel.
AB  - INTRODUCTION: The purpose of this study was to analyze historical hearing
      sensitivity data to determine factors associated with an occupationally
      significant change in hearing sensitivity in U.S. Air Force aviation-related
      personnel. METHODS: This study was a longitudinal, retrospective cohort analysis
      of audiogram records for Air Force aviation-related personnel on active duty
      during calendar year 2013 without a diagnosis of non-noise-related hearing loss.
      The outcomes of interest were raw change in hearing sensitivity from initial
      baseline to 2013 audiogram and initial occurrence of a significant threshold
      shift (STS) and non-H1 audiogram profile. Potential predictor variables included
      age and elapsed time in cohort for each audiogram, gender, and Air Force
      Specialty Code. Random forest analyses conducted on a learning sample were used
      to identify relevant predictor variables. Mixed effects models were fitted to a
      separate validation sample to make statistical inferences. RESULTS: The final
      dataset included 167,253 nonbaseline audiograms on 10,567 participants. Only the
      interaction between time since baseline audiogram and age was significantly
      associated with raw change in hearing sensitivity by STS metric. None of the
      potential predictors were associated with the likelihood for an STS. Time since
      baseline audiogram, age, and their interaction were significantly associated with
      the likelihood for a non-HI hearing profile. DISCUSSION: In this study
      population, age and elapsed time since baseline audiogram were modestly
      associated with decreased hearing sensitivity and increased likelihood for a non
      H1 hearing profile. Aircraft type, as determined from Air Force Specialty Code,
      was not associated with changes in hearing sensitivity by STS metric.Greenwell
      BM, Tvaryanas AP, Maupin GM. Risk factors for hearing decrement among U.S. Air
      Force aviation-related personnel. Aerosp Med Hum Perform. 2018; 89(2):80-86.

PMID- 29463352
TI  - Precooling and Warm-Up Effects on Time Trial Cycling During Heat Stress.
AB  - BACKGROUND: Heat stress limits endurance exercise performance. Combining
      precooling and warm-up prior to endurance exercise in the heat may exploit the
      benefits of both strategies while avoiding the potential negative consequences of
      each. This study tested the hypothesis that precooling combined with warm-up
      improves time trial cycling performance in the heat relative to either treatment
      alone. METHODS: Nine healthy men completed three 16.1-km time trials in 33
      degrees C after: 1) precooling (ice slurry and ice vest) alone (PREC); 2) warm-up
      alone (WU); or 3) PREC plus WU (COMBO). RESULTS: Tre was lower after PREC
      compared to WU throughout exercise and lower than COMBO for the first 12 km;
      COMBO was lower than WU for the first 4 km. Tsk during PREC was lower than COMBO
      and WU for the first 8 km, and lower in COMBO than WU for the first 4 km. PREC
      lowered pre-exercise heart rate relative to COMBO and WU (68 +/- 10, 106 +/- 12,
      101 +/- 13 bpm, respectively), but it increased similarly during exercise. Local
      sweat rate (SR) was lower in PREC (0.1 +/- 0.1 mg . cm-2 . min-1) than COMBO (0.5
      +/- 0.2 mg . cm-2 . min-1) and WU (0.6 +/- 0.2 mg . cm-2 . min-1) for the first 4
      km. Treatments did not differentially affect performance (PREC = 31.9 +/- 1.9
      min, COMBO = 32.6 +/- 2.7 min, WU = 33.1 +/- 2.9 min). DISCUSSION: We conclude
      precooling alone or with warm-up mitigated thermal strain during exercise, but
      did not significantly improve 16.1-km cycling time trial performance.Al-horani
      RA, Wingo JE, Ng J, Bishop P, Richardson M. Precooling and warm-up effects on
      time trial cycling during heat stress. Aerosp Med Hum Perform. 2018; 89(2):87-93.

PMID- 29463353
TI  - Aviator's Fluid Balance During Military Flight.
AB  - INTRODUCTION: A loss of 1% or more of bodyweight due to dehydration has a
      negative effect on cognitive performance, which could critically affect flight
      safety. There is no mention in the literature concerning the amounts of military
      pilots' fluid loss during flight. The aim of this study was to quantify fluid
      loss of pilots during military flight. METHODS: There were 48 aviators (mean age
      23.9) from the Israeli Air Force who participated in the study, which included
      104 training flights in various flight platforms. Bodyweight, urine specific
      gravity, and environmental heat strain were measured before and after each
      flight. Fluid loss was calculated as the weight differences before and after the
      flight. We used a univariate and one-way ANOVA to analyze the effect of different
      variables on the fluid loss. RESULTS: The mean fluid loss rate was 462 ml . h-1.
      The results varied among different aircraft platforms and depended on flight
      duration. Blackhawk pilots lost the highest amount of fluids per flight, albeit
      had longer flights (mean 108 min compared to 35.5 in fighter jets). Jet fighter
      pilots had the highest rate of fluid loss per hour of flight (up to 692 ml,
      extrapolated). CONCLUSION: Overall, at 11 flights (11%) aircrew completed their
      flight with a meaningful fluid loss. We conclude that military flights may be
      associated with significant amount of fluid loss among aircrew.Levkovsky A, Abot
      Barkan S, Chapnik L, Doron O, Levy Y, Heled Y, Gordon B. Aviator's fluid balance
      during military flight. Aerosp Med Hum Perform. 2018; 89(2):9498.

PMID- 29463354
TI  - Adrenal Stress and Physical Performance During Military Survival Training.
AB  - INTRODUCTION: The purpose of this research was to evaluate neuroendocrine and
      physical performance responses in sailors and Marines undergoing U.S. Navy
      Survival, Evasion, Resistance, and Escape (SERE) training. METHODS: Participants
      were 20 men (Age: 25.3 +/- 3.6 yr; Height: 178.1 +/- 6.1 cm; Weight: 83.7 +/-
      12.6 kg). Men were further split into high fit (N = 10) and low fit (N = 10)
      subgroups based on physical fitness test scores. Blood samples were obtained at
      baseline (T1), stress (T2), and recovery (T3) timepoints, and were analyzed for
      plasma epinephrine, plasma norepinephrine, plasma dopamine, serum cortisol, serum
      testosterone, and plasma neuropeptide Y. Vertical jump and handgrip tests were
      performed at T1 and T2. RESULTS: Stress hormone concentrations were significantly
      elevated at T2, with a concomitant reduction in testosterone concentrations. NPY
      concentrations did not increase at T2, but decreased significantly at T3.
      Subjects maintained performance on vertical jump and handgrip tests from T1 to
      T2. Significant between group differences were observed in norepinephrine (high
      fit: 3530.64 +/- 2146.54 pmol . L-1, low fit: 4907.16 +/- 3020.85 pmol . L-1) and
      NPY (high fit: 169.30 +/- 85.89 pg . ml-1, low fit: 123.02 +/- 88.86 pg . ml-1)
      concentrations at T3. CONCLUSION: This study revealed that despite significant
      increases in stress hormone concentrations in all subjects during SERE, fitter
      subjects exhibited differential hormonal responses during recovery, with quicker
      return of norepinephrine and NPY to baseline concentrations. This suggests
      physical fitness level may have a protective effect in recovery from periods of
      high stress military training.Szivak TK, Lee EC, Saenz C, Flanagan SD, Focht BC,
      Volek JS, Maresh CM, Kraemer WJ. Adrenal stress and physical performance during
      military survival training. Aerosp Med Hum Perform. 2018; 89(2):99-107.

PMID- 29463355
TI  - Prototype Development of a Tradespace Analysis Tool for Spaceflight Medical
      Resources.
AB  - INTRODUCTION: The provision of medical care in exploration-class spaceflight is
      limited by mass, volume, and power constraints, as well as limitations of
      available skillsets of crewmembers. A quantitative means of exploring the risks
      and benefits of inclusion or exclusion of onboard medical capabilities may help
      to inform the development of an appropriate medical system. A pilot project was
      designed to demonstrate the utility of an early tradespace analysis tool for
      identifying high-priority resources geared toward properly equipping an
      exploration mission medical system. METHODS: Physician subject matter experts
      identified resources, tools, and skillsets required, as well as associated
      criticality scores of the same, to meet terrestrial, U.S.-specific ideal medical
      solutions for conditions concerning for exploration-class spaceflight. A database
      of diagnostic and treatment actions and resources was created based on this input
      and weighed against the probabilities of mission-specific medical events to help
      identify common and critical elements needed in a future exploration medical
      capability. RESULTS: Analysis of repository data demonstrates the utility of a
      quantitative method of comparing various medical resources and skillsets for
      future missions. Directed database queries can provide detailed comparative
      estimates concerning likelihood of resource utilization within a given mission
      and the weighted utility of tangible and intangible resources. DISCUSSION: This
      prototype tool demonstrates one quantitative approach to the complex needs and
      limitations of an exploration medical system. While this early version identified
      areas for refinement in future version development, more robust analysis tools
      may help to inform the development of a comprehensive medical system for future
      exploration missions.Antonsen EL, Mulcahy RA, Rubin D, Blue RS, Canga MA, Shah R.
      Prototype development of a tradespace analysis tool for spaceflight medical
      resources. Aerosp Med Hum Perform. 2018; 89(2):108-114.

PMID- 29463356
TI  - Augmenting Human Performance in Remotely Piloted Aircraft.
AB  - INTRODUCTION: An experiment in a program of research supporting the sense-assess
      augment (SAA) framework is described. The objective is to use physiological
      measures to assess operator cognitive workload in remotely piloted aircraft (RPA)
      operations, and provide augmentation to assist the operator in times of high
      workload. In previous experiments, physiological measures were identified that
      demonstrate sensitivity to changes in workload. The current research solely
      focuses on the augmentation component of the SAA paradigm. This line of research
      uses a realistic RPA simulation with varying levels of workload. METHODS:
      Recruited from the Midwest region were 12 individuals (6 women) to participate in
      the experiment. The subjects were trained to perform a surveillance task and a
      tracking task using RPAs. There was also a secondary task in which subjects were
      required to answer cognitive probes. A within subjects factorial design was
      employed with three factors per task. Subjective workload estimates were acquired
      using the NASA-TLX. Performance data were calculated using a composite scoring
      algorithm. RESULTS: Augmentation significantly improved performance and reduced
      workload in both tasks. In the surveillance task, augmentation increased
      performance from 573.78 to 679.04. Likewise, augmentation increased performance
      in the tracking task from 749.39 to 791.81. Augmentation was more beneficial in
      high workload conditions than low workload conditions. DISCUSSION: The increase
      in performance and decrease in workload associated with augmentation is an
      important and anticipated finding. This suggests that augmentation should only be
      provided when it is truly needed, especially if the augmentation requires
      additional assets and/or resources.Gruenwald CM, Middendorf MS, Hoepf MR, Galster
      SM. Augmenting human performance in remotely piloted aircraft. Aerosp Med Hum
      Perform. 2018; 89(2):115-121.

PMID- 29463357
TI  - Point-of-Care Ultrasound for Pulmonary Concerns in Remote Spaceflight Triage
      Environments.
AB  - INTRODUCTION: With the development of the commercial space industry, growing
      numbers of spaceflight participants will engage in activities with a risk for
      pulmonary injuries, including pneumothorax, ebullism, and decompression sickness,
      as well as other concomitant trauma. Medical triage capabilities for mishaps
      involving pulmonary conditions have not been systematically reviewed. Recent
      studies have advocated the use of point-of-care ultrasound to screen for lung
      injury or illness. The operational utility of portable ultrasound systems in
      disaster relief and other austere settings may be relevant to commercial
      spaceflight. METHODS: A systematic review of published literature was conducted
      concerning the use of point-of-care pulmonary ultrasound techniques in austere
      environments, including suggested examination protocols for triage and diagnosis.
      RESULTS: Recent studies support the utility of pulmonary ultrasound examinations
      when performed by skilled operators, and comparability of the results to computed
      tomography and chest radiography for certain conditions, with important
      implications for trauma management in austere environments. DISCUSSION: Pulmonary
      injury and illness are among the potential health risks facing spaceflight
      participants. Implementation of point-of-care ultrasound protocols could aid in
      the rapid diagnosis, triage, and treatment of such conditions. Though operator
      dependent, ultrasound, with proper training, experience, and equipment, could be
      a valuable tool in the hands of a first responder supporting remote spaceflight
      operations.Johansen BD, Blue RS, Castleberry TL, Antonsen EL, Vanderploeg JM.
      Point-of-care ultrasound for pulmonary concerns in remote spaceflight triage
      environments. Aerosp Med Hum Perform. 2018; 89(2):122-129.

PMID- 29463358
TI  - Intravestibular Balance and Motion Sickness.
AB  - INTRODUCTION: A theory is presented to explain the major findings regarding
      motion sickness and to synthetize current theories concerning its etiology. The
      theory proposes that an imbalance in the output of the two major organs of the
      labyrinth-favoring the semicircular canals over the otolith organs-is responsible
      for most instances of motion sickness as experienced in terrestrial and
      microgravity environments. METHODS: Strengths and limitations of current theories
      are first outlined before the different roles of the canals and otoliths in the
      genesis of motion sickness symptoms are described. RESULTS: The proposed theory
      is shown to explain a large number of findings and integrate current theories.
      DISCUSSION: The role of vestibular imbalance in motion sickness may be a
      consequence of the more general differences between the canals and otoliths in
      autonomic control.Previc FH. Intravestibular balance and motion sickness. Aerosp
      Med Hum Perform. 2018; 89(2):130-140.

PMID- 29463359
TI  - Prophylactic Ankle Braces and the Kinematics and Kinetics of Half-Squat Parachute
      Landing.
AB  - INTRODUCTION: The objective of the study was to investigate the effects of
      dropping heights and prophylactic ankle braces on ankle joint biomechanics during
      half-squat parachute landing from two different heights. METHODS: There were 30
      male elite paratroopers with formal parachute landing training and more than 2 yr
      of parachute jumping experience who were recruited for this study. The subjects
      tested three different ankle brace conditions (no-brace, elastic brace, semirigid
      brace). Each subject was instructed to jump off a platform from two different
      heights of 0.4 m and 0.8 m, and land on a force plate in a half-squat posture.
      The Vicon 3D motion capture system and force plate were used to record and
      calculate kinematic and kinetic data. RESULTS: Dropping height had a significant
      effect on peak vertical ground reaction force (vGRF), maximum ankle angular
      displacement, and time to vGRF. As compared with the no-brace group, use of an
      elastic ankle brace significantly reduced peak vGRF by 18.57% and both braces
      significantly reduced the maximal angular displacements of dorsiflexion. The
      semirigid brace provided greater restriction against maximal angular displacement
      of inversion. DISCUSSION: The elastic and semirigid ankle braces both effectively
      restricted motion stability of the ankle joint in the sagittal plane, and the
      semirigid ankle brace prevented excessive inversion, although the comfort of this
      device should be improved overall.Wu D, Zheng C, Wu J, Hu T, Huang R, Wang L, Fan
      Y. Prophylactic ankle braces and the kinematics and kinetics of half-squat
      parachute landing. Aerosp Med Hum Perform. 2018; 89(2):141-146.

PMID- 29463360
TI  - Severe Arthritic Changes Following Acetabular Labral Repair and Femoroplasty in
      an Air Force Pilot.
AB  - BACKGROUND: Acetabular labral tears in the hip have become an increasingly common
      finding in active duty members due to improved diagnostic capabilities. This has
      led to a dramatic increase in operative management despite a lack of evidence to
      support clear long-term benefits. Literature review demonstrated overwhelmingly
      positive short-term outcomes for labral repairs; however, scattered case reports
      exist demonstrating debilitating outcomes in young patients, ultimately resulting
      in total hip arthroplasty. CASE REPORT: A 27-yr-old pilot originally presented
      with groin pain. Initial X-ray demonstrated a CAM lesion of the right hip and
      subsequent MRA showed an acetabular labral tear. The patient underwent open
      arthrotomy with labral repair and femoroplasty with minimal improvement in
      symptoms. Repeat imaging over 2 yr showed early onset osteoarthritis with rapid
      progression and a recurrent labral tear. Due to the significant progression of
      osteoarthritis, the patient was given the choice between a repeat labral repair
      and total hip arthroplasty. The patient elected for hip arthrotomy with labral
      repair and extensive synovectomy, which yielded minimal improvement in symptoms.
      DISCUSSION: Acetabular labral tears have become a hot topic in the field of
      orthopedics as a result of a surge in diagnoses likely due to improvements in
      imaging, most notably MRAs. This has led to considerable debate regarding how to
      best manage this condition. The literature overwhelmingly shows positive short
      term outcomes for surgical management; however, long-term follow-up studies are
      lacking. The literature has demonstrated multiple case reports resulting in
      significant complications as a result of these operations, including chondrolysis
      and eventual need for total hip arthroplasty. Therefore, patient selection is
      critical as the population tends to be young and active, and the potential
      complications can be catastrophic. In any case, it is clear that further research
      is required.Sardon CJ, Resnick ML. Severe arthritic changes following acetabular
      labral repair and femoroplasty in an air force pilot. Aerosp Med Hum Perform.
      2018; 89(2):147-150.

PMID- 29463361
TI  - You're the Flight Surgeon.
AB  - Patterson A, Rosenthal J. You're the flight surgeon: foot drop. Aerosp Med Hum
      Perform. 2018; 89(2):151-153.

PMID- 29463362
TI  - This Month in Aerospace Medicine History.

PMID- 29463363
TI  - Natural Single-Domain Antibody-Nanobody: A Novel Concept in the Antibody Field.
AB  - Since the serendipitous discovery of heavy-chain antibodies in Camelidae 20 years
      ago, the smallest single-domain antigen-binding fragment, known as VHH or
      nanobody, has received growing attention. In comparison with traditional
      antibodies, VHHs performs equally high specificity and affinity and low toxicity
      to targets, and has the ability to inhibit the formation of enzymes and enter the
      receptor gap. Hence, VHHs has been recently regarded as the highly valued protein
      and applied in multiple fields, including fundamental research, diagnosis,
      therapeutics, food science, etc. Today, based on the past achievements, an
      increasing number of academic and industrial groups begin to explore innovative
      VHH applications. In this review, we make a thorough retrospect of the unique
      features and explore novel implementations of VHHs in diverse forms in different
      fields. In addition, we also propose the potential future issues and problems of
      VHHs in many fields.

PMID- 29463364
TI  - Cutting Edge Protein and Carbohydrate-Based Materials for Anticancer Drug
      Delivery.
AB  - Materials derived from biological sources not only offer biocompatibility but
      also adjust with the disease for elongated treatments and more effective
      therapies. These materials can be utilized as building blocks to construct state
      of the art drug delivery vehicles like nanoparticles, hydrogels, and nanofibers
      capable of dramatically enhancing the therapeutic efficiency in cancer treatment.
      New emerging trends in drug delivery design are constantly reported in recent
      literature using carbohydrates like cellulose, chitosan, and alginate and
      proteins like albumin, collagen, gelatin, and zein. In addition, drug vehicles
      with combination of carbohydrates and proteins have proved extremely effective.
      This article reviews carbohydrate and protein-based materials in fabrication of
      cutting edge drug delivery systems and clarifies their future impact in
      therapeutic methods to cure cancer.

PMID- 29463365
TI  - Immunosensors Based on Nanomaterials for Detection of Tumor Markers.
AB  - Nanomaterials have been widely used to immobilize biomolecules, amplify the
      signals and concentrate the analytes for detection with good properties including
      large surface area, good adsorption capacity and high surface activity. In recent
      years, nanomaterials such as carbon nanomaterials, noble metal nanomaterials,
      polymers, are widely applied to research and develop immunosensors with high
      sensitivity and selectivity, which monitor the antigen-antibody reaction for the
      detection of tumor markers. This review provides an introduction of immunosensors
      and focuses on the design of electrochemical (EC) immunosensors, electrochemical
      luminscence (ECL) immunosensors and photoelectrochemical (PEC) immunosensors
      based on nanomaterials in nearly three years.

PMID- 29463366
TI  - The Interplay Between Nanoparticles and Neutrophils.
AB  - The employment of nanoparticles has markedly increased in recent years for
      different applications such as aerospace technology, electronics, biology, and
      medicine. The exposure of nanoparticles to humans is inevitable nowadays.
      Neutrophils act as the predominant phagocytic cells for first-line defense to be
      recruited to an inflammatory site against xenobiotics. It is important to explore
      how neutrophils interact with nanoparticles to elicit immune responses. Different
      types of nanoparticles have been studied to reveal a potential interaction to
      neutrophils in vitro and in vivo. These mainly include metallic nanoparticles,
      polymeric nanoparticles, silica nanoparticles, lipid nanoparticles, and
      fullerenes. A number of investigations have reported the toxicity of
      nanoparticles induced by neutrophil activation. In this review we discuss data
      demonstrating recently recognized aspects of inflammation induced by overwhelmed
      neutrophils after nanoparticle treatment. Besides the dark side of the
      nanoparticles, some therapeutic nanoparticles are developed and beneficial in
      treating neutrophil-related diseases such as acute lung injury, vascular
      inflammation, and bacterial infection. Some nanoparticles can recruit neutrophils
      around tumor sites for immunotherapy. We also summarize how nanoparticles
      actively target neutrophils with therapeutic aims. This review provides a broad
      introduction to nanoparticle interplay with neutrophils and discusses in vitro
      and in vivo studies in which they have been evaluated.

PMID- 29463367
TI  - An Evaluation of Graphene as a Multi-Functional Heating Element for Biomedical
      Applications.
AB  - Graphene has been found to be an excellent heat-conductor due to the high speed
      of acoustic phonons in its lattice. In this work, we examine in depth a
      commercial graphene-based waist protector which uses graphene as a heating
      element. By employing thermal imaging in tandem with Raman microscopy, the
      thermal characteristics and performance of this device is fully assessed. It will
      be shown that no pronounced variation in its function is observed up to 3 hours
      of continuous operation and that the device seems to work effectively as an IR
      emitter at low power consumption. Temperature fluctuations, associated with a
      decrease of its electrical resistance are observed after 12 hours uptime and a
      temperature difference of 15  degrees C was recorded after 5 days of
      uninterrupted operation. These effects are thought to be due to the loss of
      graphene/polymer adhesion resulting from thermal fatigue. Overall, it is
      demonstrated that graphene can indeed be incorporated as an effective and
      operational thermal heating system in similar biomedical devices.

PMID- 29463368
TI  - Preparation and Biocompatibility Evaluation of PEG-PLL/RGD-PEG
      DSPE/Phospholipid/CaP Nanoparticles.
AB  - (Arginine-Glycine-Aspartic)-methoxy polyethylene glycol-(1,2-distearoyl-sn
      glycero-3-phosphoethanolaMine-N) (abbreviation: RGD-PEG2000-DSPE or RGD-PD) was
      successfully synthesized and verified by 1H-NMR and MALDI-TOF MS. Polyethylene
      glycol-poly-L-lysine/RGD-PD/phospholipid/calcium phosphate nanoparticles (PEG
      PLL/RGD-PD/PL/CaP NPs or MNPs) were prepared using a novel, simple method
      conducted at room temperature. Transmission electron microscopy (TEM) analysis
      showed that the MNPs were spheres of uniform size, with a diameter of ~30 nm, and
      smooth surface. Thermogravimetric analysis (TGA) revealed that the PEG-PLL/RGD
      PD/PL micelle was packed in the CaP shell. MNPs had little effect on hemolysis,
      coagulation, cardiac oxidative stress, inflammatory response and DNA damage,
      indicating negligible cytotoxicity in vitro and in vivo. Experiments in Zebrafish
      indicated that the MNPs neither affected the survival rate and heartbeat rate,
      nor induced malformation and apoptosis during embryogenesis. In conclusion, these
      results demonstrate that the newly-developed MNPs have good biocompatibility and
      a great potential as drug and gene carrier.

PMID- 29463369
TI  - Glycyrrhetinic Acid-Modified Norcantharidin Nanoparticles for Active Targeted
      Therapy of Hepatocellular Carcinoma.
AB  - Norcantharidin (NCTD), the demethylated analogue of cantharidin, has been
      confirmed to have a good anti-tumor effect against hepatocellular carcinoma
      (HCC). However, its use is limited by its poor water solubility and low
      tumortargeting efficacy. In the present study, an active-targeted drug delivery
      nanoplatform was designed to deliver NCTD using a glycyrrhetinic acid (GA)
      decorated copolymer (mPEG-PCL-PEI-GA, MPG). The NCTD-loaded polymeric
      nanoparticles (MPG/NCTD) formed by self-assembly in water exhibited a mean
      hydrodynamic diameter of roughly 89 nm. In vitro studies revealed that GA
      conjugated nanoparticles (AT NPs) had superior cytotoxicity and higher targeting
      efficacy on HepG2 cells compared to non-conjugated nanoparticles (Non-AT NPs, NAT
      NPs). Determination of cell apoptosis and cell cycle phase showed that AT NPs
      resulted in increased cell apoptosis and a distinct increase in the G2 phase
      (65.30 +/- 3.52%, P < 0.01) and S phase (46.39 +/- 1.39%, P < 0.01). Evaluation
      of in vivo anti-tumor activity showed that the AT NPs significantly inhibited
      tumor growth and prolonged survival of tumor-bearing mice. The expression of Ki
      67 and CD31 revealed that AT NPs inhibited cell proliferation and resulted in a
      decreased microvessel density (MVD). The results indicated that NCTD-loaded GA
      modified nanoparticles may have great potential in HCC-targeted therapy.

PMID- 29463370
TI  - Exchangeability of FITC-SiO2 Nanoparticles Between Cancer Cells Increases the
      Range of Drug Delivery.
AB  - Drug delivery system studies aim to improve nanoparticle (NP) formulation to
      enable efficient delivery of NPs to tumors. However, NPs must be transported by
      blood or through direct injection. How NPs leave the circulatory system and how
      NPs diffuse into a tumor remain unclear, and this uncertainty is a limitation of
      drug delivery systems. The intimate connection between these questions and
      metabolism may be related to their biosafety in vivo. Thus, in this study,
      classical carrier SiO2 NPs were used as typical transport NPs, and fluorescein
      isothiocyanate (FITC) was used as the representative drug and tracer. As exosome
      and tunneling nanotubes (TNTs) are the most relevant mechanism for NP
      transportation and considering the local situation in a tumor, we focused on
      identifying this phenomenon and investigating TNTs. In conclusion, we effectively
      demonstrated that NPs can be transferred from cell to cell. Nanotubes may play an
      important role in this process.

PMID- 29463371
TI  - Enhanced In Vitro and In Vivo Anticancer Properties by Using a Nanocarrier for Co
      Delivery of Antitumor Polypeptide and Curcumin.
AB  - In this paper, a novel pH and redox dual-sensitive nanocarrier loaded with
      curcumin (Cur) and anticancer polypeptide (AP) was developed for dual targeting
      mitochondrial and CD44 receptor. The amphiphilic block copolymer was prepared by
      triphenylphosphonium (TPP)/oligomeric hyaluronic acid (oHA)/disulfide-menthone
      1,2-glycerol ketal (SM), hereinafter referred to as TPP-oHSM. The TPP targeted
      the mitochondria, pH/redox dual-sensitive SM served as a hydrophobic part, and
      the CD44 receptor targeting oHA worked as a hydrophilic part. The chemical
      structure of the TPP-oHSM was identified using 1H NMR and FTIR technologies. Cur
      and AP were loaded into the TPP-oHSM micelles by self-assembly and denoted as
      C/A@TM. The C/A@TM prepared in this study exhibited an approximately spherical
      structure, with a mean diameter of 191.3 +/- 3.1 nm and a negative zeta potential
      of -26.10 +/- 0.45 mV. The in vitro release study and cellular uptake test
      revealed that the C/A@TM targeted the mitochondria and CD44 receptor, as well as
      it showed sensitivity towards pH and redox. In addition, the C/A@TM demonstrated
      satisfactory cytotoxic effects against MDA-MB-231 cells and MCF-7 cells. Finally,
      the in vivo application of the C/A@TM showed excellent therapeutic effects. The
      C/A@TM developed in this study exhibited promising multifunctional properties as
      a co-delivery carrier of polypeptide and chemical drug for an effective clinical
      therapy for cancer.

PMID- 29463372
TI  - One-Step Synthesis of DNA Templated Water-Soluble Au-Ag Bimetallic Nanoclusters
      for Ratiometric Fluorescence Detection of DNA.
AB  - DNA strands have been used as templates to form different sized silver
      nanoclusters. Although DNA templated silver nanoclusters (NCs) probes which show
      outstanding fluorescence properties have been widely applied in chemical sensing
      and cellular imaging, synthesis of DNA template Au-Ag bimetallic nanoclusters
      remains a challenge. A facile one-step synthesis method was thus developed in
      this study to form Au-Ag NCs using C4-ATAT-C4 as template. C4-ATAT-C4 acted as a
      stabilizer for preventing aggregation of the Au-Ag NCs. The obtained Au-Ag NCs
      stabilized by C4-ATAT-C4 showed bright fluorescence and high stability. A series
      of experiments showed that temperature, citrate-citric acid buffer, sequence and
      concentration of DNA played an important role in the synthesis of fluorescent Au
      Ag NCs. In addition, a ratiometric fluorescence probe was designed through
      combining the nucleotide sequence (C4-ATAT-C4) and hybridization sequence in the
      presence of the double-strand-chelating dye Super SYBR Green (SG). The
      combination of prepared Au-Ag NCs, Super SG, and perfectly matched DNA emitted
      fluorescence at 500 and 590 nm, respectively, when the composite was excited at
      290 nm. A gastric cancer gene was also selectively detected by our developed
      ratiometric fluorescence probe.

PMID- 29463373
TI  - Novel Application of Cell Penetrating R11 Peptide for Diagnosis of Bladder
      Cancer.
AB  - OBJECTIVE: As a novel cell-permeable peptide, polyarginine (R11) showed great
      potential as contrast agent to target bladder cancer (BCa) for therapeutic
      applications. However, its diagnostic ability and uptake efficiency between BCa
      and normal bladder tissues is unknown. In this study, we investigated the
      feasibility of R11 conjugated with fluorescein isothiocyanate (FITC-R11) for
      detecting BCa in clinical practice. METHOD: FITC-R11 was synthesized and
      incubated with BCa cell lines (T24, 5637, RT4), normal immortalized human bladder
      epithelial cell line (SVHUC) and clinical specimens from BCa and benign prostate
      hyperplasia patients. The uptake efficiency was determined by the mean values of
      relative FITC intensity. Furthermore, FITC-R11 was intravesically injected into
      the athymic nude mice bearing orthotopic T24-t tumors and pulmonary metastasis of
      bladder tumor mice models, the fluorescence intensity of bladder tumors and
      normal bladder tissues was examined, as well as lung tissues. RESULT: After
      incubation with FITC-R11, the fluorescence intensity of T24, 5637, RT4 and SVHUC
      cell line was 64678.56 +/- 9699.27, 46456.22 +/- 2588.06, 33802.02 +/- 429.72 and
      17785.01 +/- 1704.36, respectively (P < 0.05). In the athymic nude mice bearing
      orthotopic T24-t tumors, FITC-R11 showed elevated accumulation in the bladder
      tumors compared with normal bladder tissues, FITC-R11 was also accumulated in the
      lung of pulmonary metastasis mice. Moreover, the uptake efficiency of FITC-R11 in
      patients' BCa tissues was much higher than in normal bladder tissues (6441.95 vs.
      1196.92, P < 0.05), as well as the urine samples of BCa patients and benign
      prostate hyperplasia patients (30250.37 vs. 4948.42, P < 0.05). CONCLUSION: As
      compared with normal bladder tissue, FITC-R11 is a more specific molecular probe
      for BCa, and has the potential application in clinical practice.

PMID- 29463374
TI  - Nano-Vesicles are a Potential Tool to Monitor Therapeutic Efficacy of Carbon Ion
      Radiotherapy in Prostate Cancer.
AB  - Exosomes are nano-vesicles that contribute to the effectiveness of many
      treatments. The aim of this study was to identify profiles of microRNA (miRNA)
      contained in serum exosomes that are differentially regulated in patients with
      prostate cancer undergoing carbon ion radiotherapy (CIRT). RNA was extracted from
      serum exosomes of eight patients with localized prostate cancer before and after
      CIRT, and miRNA was analyzed by the next generation sequencing. Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the major
      signaling pathways associated with the proliferation of prostate cancer cells,
      such as MAPK, PI3K-AKT, mTOR, and AMPK may be implicated in the mechanism of CIRT
      action. Notably, 57 miRNAs present in serum exosomes were significantly altered
      after application of CIRT. A high pre-CIRT expression level of specific miRNAs
      (miR-493-5p, miR-323a-3p, miR-411-5p, miR-494-3p, miR-379-5p, miR-654-3p, miR-409
      3p, miR-543, and miR-200c-3p) predicted therapeutic benefit of CIRT (P < 0.05).
      Post-CIRT expression of miR-654-3p and miR-379-5p was also associated with CIRT
      efficacy (P < 0.05). These results suggest that the anti-prostate cancer
      mechanisms elicited by CIRT at the molecular level may involve exosomal miRNAs.
      Furthermore, specific miRNAs in serum exosomes, particularly miR-654-3p and miR
      379-5p, may serve as promising non-invasive biomarkers predicting efficacy of
      CIRT for prostate cancer.

PMID- 29463375
TI  - Poly(lactic-co-glycolic acid)/Polycaprolactone Nanofibrous Membranes for High
      Efficient Capture of Nano- and Microsized Particulate Matter.
AB  - The incidence of many diseases is closely related to air pollution. Suspended
      particulate matter of different sizes represents a major source of environmental
      pollution. Fine particles, especially ultrafine particles smaller than 2.5 MUm,
      might be more harmful to human health because of their extremely small size,
      which enables them to penetrate human lungs and bronchi and makes them difficult
      to filter out. Therefore, the fatal risks associated with PM call for the
      development of air purification materials with high efficiency and low
      resistance. In this study, poly(lactic-co-glycolic acid) and polycaprolactone
      were used to prepare nanofibrous membranes suitable for the efficient capture of
      particulate matter formed in haze-fog episodes, especially particles smaller than
      0.5 MUm. The present nanofibrous membranes exhibit superior filtration efficiency
      for particulate matter, with a much lower pressure drop compared to typical
      commercial microfiber air filters. Thanks to the combination of small pore size,
      high porosity, and robust mechanical properties, the poly(lactic-co-glycolic
      acid)/polycaprolactone (6:4) composite membrane exhibits a high filtration
      efficiency of 97.81% and a low pressure drop of 181 Pa. These favorable features,
      combined with the easy availability and biocompatibility of the component
      materials, highlight the promising potential of the present nanofibrous membranes
      for the development of personal wearable air purifiers.

PMID- 29463376
TI  - Ciclosporin A as a Reversal Agent Against Concurrent Multidrug Resistance in
      Tumors with Nanobubbles.
AB  - The purpose of this work was to challenge the multidrug resistance (MDR) in tumor
      through nanobubbles (NB) co-loaded reversal agent and chemotherapeutic drug layer
      by layer. The core/shell NB structure contains Doxorubicin (Dox) as anticancer
      drug in the core and Ciclosporin A (CsA), a cyclic polypeptide composed of 11
      amino acids, as a reversal agent in the shell. The drug was designed to work
      against concurrent MDR processes and was defined as CsA/Dox/NB. HL60/ADM cells
      with typical high expression of multidrug resistance associated protein 1 (MRP1)
      were assessed by flow cytometer, 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assays, and Western blot analysis to observe the in
      vitro and in vivo anticancer efficacy and reversal ability of MDR. Results
      demonstrated that the function and expression of MRP1 could be successfully
      inhibited by CsA as a reversal agent from the pharmaceutical preparation, leading
      to dramatic increase of intracellular concentration of Dox. The accumulation of
      anticancer drug in the MDR cancer cells enhanced inhibition of cell proliferation
      through G2/M arrest and tumor growth of nude mice xenograft model. It was
      therefore concluded that the CsA/Dox/NB can be a promising drug candidate in
      overcoming tumor MDR.

PMID- 29463377
TI  - A Portable Multi-Channel Turbidity System for Rapid Detection of Pathogens by
      Loop-Mediated Isothermal Amplification.
AB  - This study aimed at developing a portable multi-channel turbidity system (21 cm
      in length, 15.5 cm in width and 11.5 cm in depth) by real-time loop-mediated
      isothermal amplification (LAMP) method for rapid detection of pathogens. The
      developed system herein includes temperature control unit, photoelectric
      detection unit, turbidity calibration unit, power management unit, human machine
      unit, communication unit and ARM-based microcontroller. The coefficient of
      variation for eight channels is less than 0.25% in noise analysis. Legionella
      bacteria (LEG) and H7 subtype virus (H7) were successively detected by the
      designed and developed system within 60 minutes. Moreover, its specificity for
      LEG is satisfactory and its sensitivity for H7 is 10 copies/mL. Besides, this
      system for point-of-care diagnosis allows a rapid, small size, low cost, and
      automatic detection with the characteristics of high-efficiency, excellent
      stability and high uniformity.

PMID- 29463378
TI  - Single-Nucleotide Polymorphism Genotyping of exoS in Pseudomonas aeruginosa Using
      Dual-Color Fluorescence Hybridization and Magnetic Separation.
AB  - Pseudomonas aeruginosa exoS gene contains important replacement (non-synonymous)
      single-nucleotide polymorphism (SNP) loci, of which mutations in loci 162 (G162A)
      and 434 (G434C) in exoS greatly affects virulence. The present study aimed to
      develop an SNP-based classification method for exoS loci (G162A and G434C), using
      magnetic enrichment polymerase chain reaction, magnetic separation, and dual
      color fluorescence to provide a technical basis for understanding the T3SS
      genotypic variation. The two SNP loci in 3 P. aeruginosa standard strains,
      ATCC27853, ATCC9027, and CMCC10104, were analyzed using this method. The two SNP
      loci of all these strains were found to be of the wild-type subtype. G values
      were greater than 0.8 and I values were greater than 3; hence, the classification
      yielded statistically significant results. In addition, G162A and G434C SNP loci
      in 21 clinical isolates were analyzed using this method for monitoring clinical
      mutations. In the G162A and G434C SNP loci, 57.1% and 80.9% of isolates were of
      the wild-type subtype; 23.8% and 14.3%, mutation subtype; 9.5% and 4.8%,
      heterozygous subtype, respectively. In a word, SNP genotyping of loci G162A and
      G434C in exoS was established using magnetic separation and dual-color
      fluorescence hybridization, and the method was optimized.

PMID- 29463379
TI  - Peptidomic Analysis of Female Reproductive Tract Secretion to Identify Putative
      Anti-Infection Peptides in the Female Genital System via Nanotechnologies.
AB  - The female genital system infections have high-incidence among various
      gynecological diseases. The role of endogenous peptides in female reproductive
      tract secretion has been rarely investigated regarding gynecological infections.
      To identify gynecological infections associated endogenous peptides, a
      comparative peptidomic profiling of vaginal secretion from sexually mature and
      perimenopause women was conducted in this study using nanoflow liquid
      chromatography-tandem mass spectrometer. A total of 3096 peptide fragments
      originating from 1364 precursor proteins were identified, 102 of which were
      discrepantly expressed, which included 60 over-expressed peptides and 42 under
      expressed peptides in the sexually mature group compared with the perimenopause
      group. 6 differentially expressed bioactive peptides were identified to be
      related to immunodeficiency virus (HIV) infections, human papillomavirus (HPV)
      infections, bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). MUC4,
      MUC5A, MUC5B, MUC6, MUC17 and MUC19 peptides originating from mucin family were
      identified to enhance vaginal mucous immunity against infections. Moreover, with
      remarkable development of biomedical nanotechnology, the identified potential
      anti-infection peptides in our study will be useful in diagnosis and treatment of
      gynecological infections, especially when combined with nanoparticles. In
      conclusion, our findings will fill the gap on peptidomics for female genital
      system infections and pave the way for future studies about reproductive tract
      diseases management.

PMID- 29463380
TI  - Metronidazole-Loaded Polyethyleneimine and Chitosan-Based Liquid Crystalline
      System for Treatment of Staphylococcal Skin Infections.
AB  - Staphylococcus aureus is a common gram-positive bacterium of the human skin
      microbiota. It is also a dangerous pathogen that can cause serious and even
      lethal skin infections. The topical administration of metronidazole via
      nanotechnology-based drug delivery systems, such as liquid crystalline systems,
      can modulate both the drug permeation and activity, decreasing its side effects
      and increasing the drug potent activity against the gram-positive bacteria. This
      study aimed at: (1) structurally developing and characterizing a liquid
      crystalline systems composed of chitosan and polyethyleneimine dispersion as the
      aqueous phase, oleic acid as the oily phase, and ethoxylated and propoxylated
      cetyl alcohol as the surfactant (FPC) for metronidazole incorporation (0.5% w/w);
      (2) evaluating the in vitro release and skin permeation and retention properties
      of the metronidazole-loaded liquid crystalline systems (FPC-M); (3) investigating
      the in vitro antibacterial activity of FPC-M against Staphylococcus aureus.
      Polarised light microscopy indicated that both FPC and FPC-M are hexagonal
      systems. Rheological, texture, and bioadhesion assays showed that both are
      elastic and bioadhesive systems. According to the results of the in vitro
      release, permeation, and retention assays, FPC can modulate metronidazole release
      and allow metronidazole to stay for a longer time on the skin. The determination
      of FPC-M activity against Staphylococcus aureus showed that it could target the
      bacterial cell. In conclusion, the liquid crystalline systems developed in this
      study can improve the clinical performance of metronidazole in the treatment of
      staphylococcal skin infections.

PMID- 29463381
TI  - Photocarcinogenic Risk Associated With Narrowband UV-B Phototherapy: An
      Epidemiologic Study in a Tertiary Care Hospital.
AB  - BACKGROUND: The risk of skin cancer in patients treated with narrowband (NB) UV-B
      phototherapy is not well understood. Although experimental studies have shown
      that there is a risk, clinical studies have not detected an increased incidence
      of cancer following treatment. The aim of this study was to determine the
      incidence of nonmelanoma skin cancer (NMSC) in patients treated with NB UV-B
      phototherapy at a tertiary care hospital in the Mediterranean area. MATERIAL AND
      METHODS: We conducted a retrospective chart review of 474 patients who received
      whole-body NB UV-B phototherapy at our hospital between 2002 and 2016 and
      identified those diagnosed with NMSC during follow-up. We calculated the
      corresponding crude and standardized incidence rates and compared these with
      rates in the general population in a similar geographic area. RESULTS: Of the 474
      patients, 193 (40.7%) were men and 281 (59.3%) were women. The mean (SD) follow
      up period was 5.8 (3) years. The prevalence of NMSC at the end of the study
      period was 1.9% and the standardized incidence was 108.3 cases per 100 000
      patient-years. The SIR of 1.9 in the study group was not significantly different
      from that of the general population. The number of patients who needed to be
      treated with NB UV-B phototherapy for 1 case of NMSC to occur was 1900.
      CONCLUSION: NB UV-B phototherapy does not appear to be associated with an
      increased risk of NMSC.

PMID- 29463382
TI  - Clinical and non-clinical factors that predict discharge disposition after a
      fall.
AB  - BACKGROUND: Falls can result in injuries that require rehabilitation and long
      term care after hospital discharge. Identifying factors that contribute to
      prediction of discharge disposition is crucial for efficient resource utilization
      and reducing cost. Several factors may influence discharge location after
      hospitalization for a fall. The aim of this study was to examine clinical and non
      clinical factors that may predict discharge disposition after a fall. We
      hypothesized that age, injury type, insurance type, and functional status would
      affect discharge location. METHODS: This two-year retrospective study was
      performed at an urban, adult level-1 trauma center. Fall patients who were
      discharged home or to a facility after hospital admission were included in the
      study. Data was obtained from the trauma registry and electronic medical records.
      Logistic regression modeling was used to assess independent predictors. RESULTS:
      A total of 1,121 fallers were included in the study. 621 (55.4%) were discharged
      home and 500 (44.6%) to inpatient rehabilitation (IRF)/skilled nursing facility
      (SNF). The median age was 64 years (IQR: 49-79) and 48.4% (543) were male. The
      median length of hospital stay was 5 days (IQR: 2.5-8). Increasing age (p <
      0.001), length of stay in the ICU (p < 0.001), injury severity (p < 0.001),
      number of comorbidities (p = 0.038), having Medicare insurance (p = 0.025),
      having a fracture at any body region (p < 0.001), and ambulation status (p =
      0.025) significantly increased the odds of being discharged to IRF/SNF compared
      to home. The removal of injury severity score and ICU length of stay from the
      "late/regular discharge" model, to create an "early discharge" model, decreased
      the accuracy of the prediction rate from 78.5% to 74.9% (p < 0.001). CONCLUSION:
      A combination of demographic, clinical, social, economic, and functional factors
      can together predict discharge disposition after a fall. The majority of these
      factors can be assessed early in the hospital stay, which may facilitate a timely
      discharge plan and shorter stays in the hospital.

PMID- 29463383
TI  - Reply.

PMID- 29463384
TI  - The evaluation of depression in multiple sclerosis using the newly proposed
      Multiple Sclerosis Depression Rating Scale.
AB  - Fatigue and depression are frequent symptoms in multiple sclerosis (MS). Both are
      overlapping and shadowing each other and may impair the quality of life. For
      detection of depression symptoms in MS, the Multiple Sclerosis Depression Rating
      Scale (MSDRS) has been proposed recently. Here, we compare the performance of
      MSDRS in MS patients with and without fatigue to that of established rating
      scales, i.e. Hospital Anxiety and Depression Scale and Beck Depression Inventory.
      Twenty-nine MS patients were screened for fatigue and depression symptoms.
      Patients with fatigue showed significantly higher depression scores compared to
      patients without fatigue, whereas the number of depressed patients did not differ
      between the two groups. MSDRS seems to have higher sensitivity to detect severe
      depression than established rating scales. However, one should keep in mind that
      such a finding might be due to an increase in false positive cases when using
      MSDRS. Implementing this scale in future studies might be of help to enhance the
      understanding of its potential utility.

PMID- 29463385
TI  - A comparison of methods to determine center of mass during pregnancy.
AB  - Balance changes during pregnancy likely occur because of mass gains and mass
      distribution changes. However, to date there is no way of tracking balance
      through center of mass motion because no method is available to identify of the
      body center of mass throughout pregnancy. We compared methods for determining
      segment masses and torso center of mass location. The availability of a method
      for tracking these changes during pregnancy will make determining balance changes
      through center of mass motion an option for future pregnancy balance research.
      Thirty pregnant women from eight weeks gestation until birth were recruited for
      monthly anthropometric measurements, motion capture analysis of body segment
      locations, and force plate analysis of center of pressure during quiet standing
      and supine laying. From these measurements, we were able to compare regression,
      volume measurement, and weighted sum methods to calculate body center of mass
      throughout pregnancy. We found that mass changes around the trunk were most
      prevalent as expected, but mass changes throughout the body (especially the
      thighs) were also seen. Our findings also suggest that a series of anthropometric
      measurements first suggested by Pavol et al. (2002), in combination with quiet
      standing on a force plate, can be used to identify the needed components (segment
      masses and torso center of mass location in three dimensions) to calculate body
      center of mass changes during pregnancy. The results of this study will make
      tracking of center of mass motion a possibility for future pregnancy balance
      research.

PMID- 29463386
TI  - Effects of tracking landmarks and tibial point of resistive force application on
      the assessment of patellar tendon mechanical properties in vivo.
AB  - The different methods used to assess patellar tendon elongation in vivo may
      partly explain the large variation of mechanical properties reported in the
      literature. The present study investigated the effects of tracking landmark
      position and tibial point of resistive force application during leg extensions in
      a dynamometer. Nineteen adults performed isometric contractions with a proximal
      and distal dynamometer shank pad position. Knee joint moments were calculated
      employing an inverse dynamics approach. Tendon elongation was measured using the
      patellar apex and either the tibial tuberosity (T) or plateau (P) as tracking
      landmark. Using P for tracking introduced a bias towards greater values of tendon
      elongation at all force levels from 100 N to maximum tendon force (TFmax; p <
      0.05). The differences between landmarks considering maximum tendon strain were
      greater at the proximal shank pad position (p < 0.05). Tendon stiffness was lower
      for P compared with T, but only in intervals up to 50% of TFmax (p < 0.05). The
      agreement between T and P for stiffness calculated between 50% and TFmax was
      acceptable with the distal, but poor with the proximal pad position. We
      demonstrated that using the tibia plateau and not the insertion as tracking
      landmark clearly affects the assessment of the force-elongation curve of the
      patellar tendon. However, using a distal point of resistive force application and
      calculating tendon stiffness between 50% and TFmax seems to yield an acceptable
      agreement between landmarks. These findings have important implications for the
      assessment of tendon properties in vivo and cross-study comparisons.

PMID- 29463387
TI  - The high frequency of autoantibodies in HIV patients declines on antiretroviral
      therapy.
AB  - Autoantibodies have been described in samples from HIV positive patients, but the
      effects of antiretroviral therapy (ART) remain unclear. In a retrospective
      longitudinal study, we applied clinical assays for autoantibodies to sera
      collected from 13 HIV positive patients as they began ART with <210 CD4 T
      cells/MUL and over 2 years on treatment. Twelve of the 13 patients had at least
      one autoantibody. The frequency peaked before ART (21 from 156 assays) and
      declined to 8/143 positive reactions after 2 years. As anti-smooth muscle (ASM)
      antibodies remained common, these assays were applied to HIV patients (n = 67)
      who had <50 copies HIV RNA/mL plasma after 13 (2-17) years on ART, and healthy
      controls (n = 55). The frequency of ASM was high in these patients and correlated
      with levels of total IgG. Hence the high frequency of autoantibodies before ART
      declined, but did not disappear, with successful therapy. Autoantibody levels may
      reflect B-cell hyperactivity in patients stable on ART.

PMID- 29463388
TI  - Vascular inflammation: A call for a specific and sensitive biomarker?

PMID- 29463389
TI  - Trauma in pregnancy.
AB  - Trauma is the leading non-obstetric cause of death during pregnancy and
      approximately 6-8% of all pregnancies are complicated by injury, both accidental
      and intentional. The initial evaluation and management of the injured pregnant
      patient often requires a multidisciplinary, collaborative team to provide the
      optimal outcome for both mother and fetus. It is important to recognize that even
      minor mechanisms of injury may result in poor outcomes for both fetus and mother.
      Injured pregnant patients meeting admission criteria experience a progressive
      increase in the number of complications as well as the number of patients that
      require delivery. There exists opportunity to identify patients who require
      admission and provide supportive measures that may reduce the complications of
      prematurity. Patients that are admitted may benefit from a multidisciplinary
      approach including on-going care from obstetricians or maternal-fetal medicine
      physicians. Placental abruption is the most common pregnancy complication, and
      may occur with even minor mechanisms of injury. Increasing severity of trauma
      increases the frequency of abruption, admission, delivery, and fetal demise.

PMID- 29463390
TI  - Managing congenital heart disease in the obstetric patient.
AB  - OBJECTIVE: Cardiovascular disease is the major cause of pregnancy-related
      maternal mortality in the United States, and congenital heart disease (CHD) is
      the most common form of structural heart disease affecting women of childbearing
      age. Most females born with CHD will reach childbearing age and consider
      pregnancy. Adult CHD and maternal-fetal medicine (MFM) specialists managing women
      with CHD should provide preconception counseling, cardiovascular risk assessment
      prior to pregnancy that estimates maternal and fetal risk, management during
      pregnancy, and in the peripartum period and also know the potential complications
      and special circumstances that may occur in the post-partum period. This chapter
      will review the population at risk, patient risk prior to pregnancy, management
      during pregnancy, management in the peripartum and post-partum periods, and
      outline specific cardiovascular complications. The chapter will also briefly
      review some common or high-risk congenital cardiovascular lesions commonly
      encountered. CONCLUSION: Management of patients with most forms of CHD
      encountered during pregnancy requires a multidisciplinary approach and careful
      team-based care to facilitate safe and appropriate management and pregnancy
      success.

PMID- 29463391
TI  - Maternal sepsis.
AB  - Sepsis is a leading cause of maternal morbidity and mortality in developed and
      developing nations. Obstetric practitioners should be familiar with guidelines
      that promote the safe and expeditious recovery of those affected. This article
      will provide the reader with rational steps to aid in the recovery of such a
      patient.

PMID- 29463393
TI  - ?
AB  - The nutrition care of patients with chronic kidney disease (CKD) remains a
      central question which is permanently studied. The benefits of a dietary protein
      restriction are once again enlightened, either by reducing the urea found to be
      hyperglycemic, thus improving the peripheric insulin sensitivity, or by
      decreasing phosphorus and FGF23 hormone, whose reductions are respectively
      associated with nephroprotection and diminution of cardiovascular events. The
      numerous researches conducted on the gut microbiota also open promising avenues
      to better understand the role of this ecosystem in CKD. Finally, the interest in
      incremental haemodialysis is revived, results show it may be associated with less
      loss of proteins and preservation of residual kidney function. The development of
      a nutritional score, informative of survival prediction, also offers the
      possibility to ensure a better follow-up of patients.

PMID- 29463394
TI  - ?
AB  - Hypertension is common in patients with chronic renal disease particularly those
      with diabetes. It is sometimes resistant to the pharmacological treatment. The
      mineralocorticoid receptor antagonist spironolactone may be indicated here. The
      mineralocorticoid receptor antagonists have a Class 1, Level A indication for the
      treatment of heart failure with reduced ejection fraction. There is an associated
      risk of worsening renal function and of hyperkalemia which does not hinder their
      clinical benefit. However, an appropriate biological monitoring is warranted,
      along with potential dose adaptations. Cardiorenal syndrome significantly worses
      the prognosis of congestive heart failure. The use of ultrafiltration can be
      effective when conventional treatments failed. Its place in the front line needs
      to be evaluated.

PMID- 29463395
TI  - [Cardiovascular protection of diabetic patient with chronic renal disease and
      particular case of end-stage renal disease in elderly patients].
AB  - Type 2 diabetes has an increasing prevalence. Life expectancy is dominated by
      cardiovascular risk, which is the leading cause of death in these patients. Up to
      one third of diabetic patients will develop diabetic nephropathy related to micro
      angiopathy. Renal impairment further increases cardiovascular risk. Reducing
      cardiovascular morbidity and mortality is a major public health issue, as well as
      early preventing and managing chronic kidney disease (CKD). Good glycemic control
      prevents the micro-vascular complications of the disease (retinopathy,
      nephropathy, etc.) and, more recently recognized through prolonged monitoring of
      the VADT cohort, prevents cardiovascular complications. Control of blood pressure
      and dyslipidemia are essential in primary or secondary cardiovascular prevention.
      In addition, the blockers of the renin-angiotensin system slow down the
      progression of the MRC. Elderly patients with chronic kidney disease (CKD) form
      another growing group of the nephrologist daily patient pool. Especially for very
      elderly patients with comorbidities, the question of favoring conservative
      treatment rather than starting or pursuing dialysis may arise. Survival and
      quality of life are indeed not necessarily better in elderly patients undergoing
      dialysis, complications can occur eventually leading to discontinuation, and are
      occasionally associated with a feeling of stubbornness. Creation of prognostic
      score is a useful tool to help the decision-making process. However, dialogue
      with the patient and his/her family, as well as multidisciplinary collaboration
      remain fundamentals to determine the most suitable care.

PMID- 29463396
TI  - [Renal transplantation].
AB  - Renal transplantation is the best option for patients with end stage renal
      failure, since it significantly improves their duration and quality of life. The
      number of patients waiting for a kidney transplant continues to increase while
      the overall rate of organ procurement in France is stable. The graft shortage is
      worsening, as is the waiting time on list. Identifying the causes of this crisis
      and discussing the various options for addressing the kidney graft shortage is
      the aim of this talk. Among the solutions: (i) improving identification of
      potential donors through a national and hospitals policy to promulgate organ
      donation and understanding better the grounds for refusal; (ii) using infusion
      machines for all grafts with extended criteria; (iii) developing transplantation
      programs from deceased donors after cardiac arrest; (iv) developing
      transplantation programs from living donors.

PMID- 29463397
TI  - [Metabolic complications of chronic kidney disease].
AB  - Patients with Chronic Kidney Disease (CKD) are at risk of various metabolic
      complications, which can lead to health issues and even be life-threatening if
      not correctly treated, whereas they can be anticipated. Through clinical cases of
      patients taken from the daily practice, we propose to look into three of these
      common complications, namely hypocalcemia, hyperkalemia and metabolic acidosis.
      From the diagnostic approach to the patient care, these cases provide the
      opportunity to recall the fundamentals of these disorders and to present the
      recent literature date enlightening the knowledge related to them.

PMID- 29463399
TI  - Editorial overview: Cell differentiation and development: New kids in the block
      new tools and concepts opening new doors in development.

PMID- 29463398
TI  - ?
AB  - Erythropoietin (EPO) plays an essential role in the regulation of erythropoiesis.
      Its production is under the control of the Hypoxia Inducible Factor (HIF) protein
      whose stability varies according to the oxygen level. During chronic renal
      failure, EPO deficiency is the main cause of anemia, but other factors such as
      iron deficiency and inflammatory syndrome are also involved. More recently, it is
      hypothesized that other factors such an excess of GDF-11 production may be also
      involved. Thus, beside Epo treatment HIF and GDF-11 are potentially new
      therapeutic targets in anemia of chronic kidney disease.

PMID- 29463400
TI  - Foreword.

PMID- 29463402
TI  - Transcriptome-based identification and characterization of genes commonly
      responding to five different insecticides in the diamondback moth, Plutella
      xylostella.
AB  - When the 3rd instar larvae of the diamondback moth (DBM), Plutella xylostella,
      were pretreated with sublethal doses (LC10) and then subsequently exposed to
      lethal doses (LC50) of chlorantraniliprole, cypermethrin, dinotefuran, indoxacarb
      and spinosad via leaf dipping, their tolerance to insecticides was significantly
      enhanced. To identify genes that commonly respond to the treatment of different
      insecticides and are responsible for the tolerance enhancement, transcriptomic
      profiles of larvae treated with sublethal doses of the five insecticides were
      compared with that of untreated control. A total of 117,181 transcripts with a
      mean length of 662bp were generated by de novo assembly, of which 35,329
      transcripts were annotated. Among them, 125, 143, 182, 215 and 149 transcripts
      were determined to be up-regulated whereas 67, 45, 60, 60 and 38 genes were down
      regulated following treatments with chlorantraniliprole, cypermethrin,
      dinotefuran, indoxacarb and spinosad, respectively. Gene ontology (GO) analysis
      of differentially expressed genes (DEGs) revealed little differences in their GO
      profiles between treatments with different insecticides except for spinosad.
      Finally, the DEGs commonly responding to all insecticides were selected for
      further characterization, and some of their over-transcription levels were
      confirmed by quantitative PCR. The most notable examples of commonly responding
      over-transcribed genes were two cytochrome P450 genes (Cyp301a1 and Cyp9e2) and
      nine cuticular protein genes. In contrast, several genes composing the
      mitochondrial energy generation system were significantly down-regulated in all
      treated larvae. Considering the distinct structure and mode of action of the five
      insecticides tested, the differentially expressed genes identified in this study
      appear to be involved in general chemical defense at the initial stage of
      intoxication. Their possible roles in the tolerance/resistance development were
      discussed.

PMID- 29463403
TI  - Metabolisation of thiamethoxam (a neonicotinoid pesticide) and interaction with
      the Chronic bee paralysis virus in honeybees.
AB  - Pathogens and pesticides are likely to co-occur in honeybee hives, but much
      remains to be investigated regarding their potential interactions. Here, we first
      investigated the metabolisation kinetics of thiamethoxam in chronically fed
      honeybees. We show that thiamethoxam, at a dose of 0.25ng/bee/day, is quickly and
      effectively metabolised into clothianidin, throughout a 20day exposure period.
      Using a similar chronic exposure to pesticide, we then studied, in a separate
      experiment, the impact of thiamethoxam and Chronic bee paralysis virus (CBPV) co
      exposure in honeybees. The honeybees were exposed to the virus by contact,
      mimicking the natural transmission route in the hive. We demonstrate that a high
      dose of thiamethoxam (5.0ng/bee/day) can cause a synergistic increase in
      mortality in co-exposed honeybees after 8 to 10days of exposure, with no increase
      in viral loads. At a lower dose (2.5ng/bee/day), there was no synergistic
      increase of mortality, but viral loads were significantly higher in naturally
      dead honeybees, compared with sacrificed honeybees exposed to the same
      conditions. These results show that the interactions between pathogens and
      pesticides in honeybees can be complex: increasing pesticide doses may not
      necessarily be linked to a rise in viral loads, suggesting that honeybee
      tolerance to the viral infection might change with pesticide exposure.

PMID- 29463401
TI  - Niche signals and transcription factors involved in tissue-resident macrophage
      development.
AB  - Tissue-resident macrophages form an essential part of the first line of defense
      in all tissues of the body. Next to their immunological role, they play an
      important role in maintaining tissue homeostasis. Recently, it was shown that
      they are primarily of embryonic origin. During embryogenesis, precursors
      originating in the yolk sac and fetal liver colonize the embryonal tissues where
      they develop into mature tissue-resident macrophages. Their development is
      governed by two distinct sets of transcription factors. First, in the pre
      macrophage stage, a core macrophage program is established by lineage-determining
      transcription factors. Under the influence of tissue-specific signals, this core
      program is refined by signal-dependent transcription factors. This nurturing by
      the niche allows the macrophages to perform tissue-specific functions. In the
      last 15 years, some of these niche signals and transcription factors have been
      identified. However, detailed insight in the exact mechanism of development is
      still lacking.

PMID- 29463405
TI  - Resistance risk assessment for fluazinam in Sclerotinia sclerotiorum.
AB  - In the current study, sensitivity distribution of Sclerotinia sclerotiorum
      populations to fluazinam was determined using 103 strains collected from the
      fields of Jiangsu Province of China in 2016-2017 and the resistance risk of
      fluazinam was assessed. The average EC50 (50% effective concentration) values and
      MIC (minimum inhibitory concentration) values of 103 S. sclerotiorum strains
      against fluazinam were 0.0073+/-0.0045MUg/ml and <0.3MUg/ml for mycelial growth,
      respectively. Nine mutants with low resistance level were obtained from wild type
      sensitive strains exposed on PDA medium amended with fluazinam and the resistance
      was stable after their ten transfers on PDA without the fungicide. Compared with
      the parental strains, the nine fluazinam-resistant mutants decreased in mycelial
      growth, sclerotial production, pathogenicity and were more sensitive to 0.7M
      NaCl. In addition, cell membrane permeability of resistant mutants was higher
      than that of their parental strains. Cross resistance assay showed that there was
      no cross-resistance between fluazinam and fludioxonil, dimetachlone, prochloraz,
      tebuconazole, azoxystrobin, or procymidone in S. sclerotiorum. The above results
      indicated that there was a low resistance risk for fluazinam in S. sclerotiorum.
      However, the sensitivity of all fluazinam-resistant mutants to fludioxonil
      decreased. Sequencing alignment results showed that there were no mutations in
      the two-component histidine kinase gene (Shk1) of the resistant mutants and the
      expression levels of Shk1 of three resistant mutants were significantly up
      regulated while others were almost the same as their parental strains. These
      results will contribute to evaluating the resistance risk of fluazinam for
      management of diseases caused by S. sclerotiorum and further increase our
      understanding about the mode of action of fluazinam.

PMID- 29463404
TI  - Cytotoxicity of chemical constituents from Torricellia tiliifolia DC. on
      Spodoptera litura (SL-1) cells.
AB  - In this study, we evaluated cytotoxicity of chemicals isolated from Torricellia
      tiliifolia DC. on Spodoptera litura (SL-1) cell line. Among the isolated
      compounds, 4-hydroxy-3-methoxycinnamaldehyde, 3,5-dimethoxy-4
      hydroxycinnamaldehyde, and syringaresinol inhibited SL-1 cell survival in both
      dose- and time-dependent manners. Meanwhile, the in vivo insecticidal activity
      test revealed that 4-hydroxy-3-methoxycinnamaldehyde and 3,5-dimethoxy-4
      hydroxycinnamaldehyde showed obvious insecticidal activities. These two compounds
      exhibited toxicity to SL-1 cells by inducing cellular morphological changes
      including shape change, cell shrinkage, vacuolation, cell membrane blebbing and
      chromatin condensation and apoptosis. 4-hydroxy-3-methoxycinnamaldehyde and 3,5
      dimethoxy-4-hydroxycinnamaldehyde showed the most effect on mitochondrial
      membrane depolarization at 24h and 72h respectively and induced the apoptosis at
      a late time point 72h. Our results suggest that 4-hydroxy-3-methoxycinnamaldehyde
      and 3,5-dimethoxy-4-hydroxycinnamaldehyde inhibit SL-1 survival by inducing
      apoptosis.

PMID- 29463406
TI  - Chlorpyrifos-induced parkinsonian model in mice: Behavior, histopathology and
      biochemistry.
AB  - INTRODUCTION: The aim of this study was to investigate the protective effect of
      caffeic acid phenethyl ester (CAPE) on Paraoxonase (PON1) activity, and levels of
      lipid profile, total sialic acid (TSA), total antioxidant capacity (TAC) and
      total oxidant capacity (TOC) in the plasma and brain tissue of mice with
      chlorpyrifos-ethyl (CPF)-induced Parkinson. MATERIAL AND METHOD: In the study, 35
      male Swiss albino mice were divided into 5 groups including equal number of mice
      as follows; intraperitoneal injection of saline for mice in control (C) group,
      subcutaneous injection of 80mg/kg CPF for CPF group, intraperitoneal injection of
      10MUmol/kg CAPE for CAPE group, subcutaneous injection of 80mg/kg CPF and
      intraperitoneal injection of 10MUmol/kg CAPE for CPF+CAPE group and
      intraperitoneal injection of 10% ethanol diluted in physiological saline solution
      for 21days for ethanol (E) group. All the mice were fed with normal feed and tap
      water ad libitum. At the end of the study, PON1 activity, lipid profile (except
      for brain), and TSA, TAC and TOC levels in the plasma and brain tissue were
      analyzed. Tissue samples of brain substantia nigra were evaluated
      histopathologically. RESULTS: Levels of plasma TAC, high density lipoprotein
      (HDL) and PON1 activity were statistically lower in CPF group than the other
      groups (P<0.001). Also, levels of plasma TOC, TSA, total cholesterol,
      triglycerides, low density lipoprotein (LDL) and very low density lipoprotein
      (VLDL) were statistically higher in CPF group than the other groups(P<0.001).
      PON1 activity and level of TAC were significantly lower in brain tissue of CPF
      groups (P<0.001). In addition, TOC and TSA levels were significantly higher in
      brain tissue in CPF group (P<0.001). CONCLUSION: In conclusion, CAPE showed a
      protective effect on PON1 activity and levels of lipid profile, TSA, TAC and TOC
      in plasma and brain tissue and prevented the neurodegenerations in brain tissue
      in CPF-induced Parkinson's disease.

PMID- 29463407
TI  - Effect of genetic polymorphism of human CYP2B6 on the metabolic activation of
      chlorpyrifos.
AB  - Chlorpyrifos (CPS) is a broad-spectrum organophosphate insecticide that is
      neurotoxic in humans. Chlorpyrifos oxon (CPO) is a toxic metabolite of CPS that
      is produced by CYP2B6. In this study, we examined the variability of CPS
      metabolism resulting from single-nucleotide polymorphisms in CYP2B6. Wild-type
      CYP2B6 (CYP2B6.1) and two variants each with a single amino acid substitution:
      CYP2B6.5 (R487C) and CYP2B6.8 (K139E) were co-expressed together with human NADPH
      dependent cytochrome P450 reductase in Escherichia coli (E. coli). Both of the
      CYP2B6 variants were successfully expressed in E. coli. The conversion of CPS to
      CPO by the CYP2B6 variants was analyzed with high-performance liquid
      chromatography. Km and Vmax of the reaction by CYP2B6.1 were 18.50+/-2.94MUM and
      17.07+/-1.15mol/min/mol P450, respectively. The CYP2B6 variants produced CPO with
      the following kinetic parameters: Km for CYP2B6.5 and CYP2B6.8 were 20.44+/-6.43
      and 44.69+/-9.97MUM, respectively; and Vmax were 1.10+/-0.10 and 1.77+/
      0.26mol/min/mol P450, respectively. These results indicate that the amino acid
      substitutions in the CYP2B6 variants suppressed the metabolic activation of CPS.
      CYP2B6 variants have altered capacity to bioactivate CPF and may affect
      individual susceptibility of CPF.

PMID- 29463408
TI  - Synthesis, characterization and efficacy of silver nanoparticles against Aedes
      albopictus larvae and pupae.
AB  - Silver nanoparticles have been studied in a wide range of medical and
      entomological research works due to their eco-friendly aspects. In our study
      salicylic acid (SA) and its derivative, 3,5-dinitrosalicylic acid (DNS), were
      used in a one-step synthesis of silver nanoparticles (AgNPs). First, UV-vis
      absorption spectroscopy was used to detect the formation of AgNPs. Second, the
      synthesized nanoparticles were characterized using scanning electron microscope,
      transmission electron microscope; energy-dispersive spectroscopy, X-ray
      diffraction analysis and Fourier transform infrared spectroscopy. I, II, III and
      IV Instar larvae and pupae of Ae. Albopictus were exposed to various
      concentrations of SA, DNS and synthesized AgNPs for 24h to evaluate the
      larvicidal and pupicidal effect. In larvicidal bioassay of SA, moderate mortality
      was observed at 180ppm against Ae. Albopictus with LC50 values of 86, 108, 135
      and 141ppm for instar larvae I, II, III and IV, respectively. Synthesized AgNPs
      showed highest mortality rate at 12ppm and the LC50 values of SAAgNPs were 1.2ppm
      (I), 1.4ppm (II), 1.8ppm (III), 2.0ppm (IV) and 1.4ppm (pupae). Whereas LC50
      values of DNSAgNPs were 1.2ppm (I), 1.5ppm (II), 1.8ppm (III) 2.3ppm (IV) and
      1.4ppm (pupae). Moreover, the investigations toward the systemic effect of the
      tested substances on the fourth instar larvae of Ae. albopictus was evaluated and
      the levels of total proteins, esterases, acetylcholine esterase, and phosphatase
      enzymes were found to be significantly decreased as compared with the control.
      These results highlight that SA-AgNPs and DNS-AgNPs are potential tools to
      control larval populations of mosquito.

PMID- 29463409
TI  - Sublethal effects of sulfoxaflor on biological characteristics and vitellogenin
      gene (AlVg) expression in the mirid bug, Apolygus lucorum (Meyer-Dur).
AB  - The mirid bug, Apolygus lucorum (Meyer-Dur) has evolved the resistance towards
      some traditional insecticides, especially pyrethroids and organophosphates.
      Sulfoxaflor, as a novel insecticide, is used for control of sap-feeding insects,
      like A. lucorum. Therefore, it is necessary to determine the acute toxicity and
      the potential sublethal effects of sulfoxaflor in A. lucorum. Here, the LD50
      value of sulfoxaflor against A. lucorum was assayed as 3.347ng/adult at 48h via
      topical application. Besides, the effects of a sublethal dose (LD15) of
      sulfoxaflor on biological characteristics of A. lucorum were estimated by
      comparison of the life table parameters. The longevities and fecundity of parent
      generation did not exhibited significant difference between both control and
      treatment groups after exposure to LD15 dose of sulfoxaflor (0.568ng/adult) for
      48-h. However, the parameters reflecting their progeny G1 generation population
      dynamics, including the intrinsic rate of increase (ri), the finite rate of
      increase (lambda), the mean generation time (T), the net reproductive rate (R0)
      and gross reproduction rate (GRR) significantly reduced in the treatment group
      compared to the control. Furthermore, the expression level of AlVg mRNA
      significantly decreased by 43.8% in the progeny whose parents were treated with
      LD15 dose of sulfoxaflor in comparison with the control transgenerational female
      adults. These results suggested that sublethal dose of sulfoxaflor adversely
      affect the development and reproduction of transgenerational A. lucorum. The
      downregulation of AlVg might have negative impacts on the fecundity of A.
      lucorum.

PMID- 29463410
TI  - Alterations of mitochondrial electron transport chain and oxidative stress
      induced by alkaloid-like alpha-aminonitriles on Aedes aegypti larvae.
AB  - Aedes aegypti mosquitoes are responsible for dengue, chikungunya, and Zika virus
      transmission in tropical and subtropical areas around the world. Due to the
      absence of vaccines or antiviral drugs for human treatment, the majority of
      control strategies are targeted at Ae. aegypti elimination. Our research on
      mosquito control insecticidal agents has previously shown that the alkaloid
      girgensohnine and its analogues (alpha-aminonitriles) present in vitro
      acetylcholinesterase inhibition and in vivo insecticidal activity against Ae.
      aegypti. However, acetylcholinesterase inhibition may not be the only mechanism
      of action behind these effects. On this basis, the principal aim of this study
      was to elucidate the possible action mode of four alpha-aminonitriles on Ae.
      aegypti by studying other important enzymatic targets, such as mitochondrial
      electron transport chain complexes, catalase, and superoxide dismutase, key
      oxidative stress enzymes. Mitochondria were isolated from Ae. aegypti larvae by
      differential centrifugation, stored at -70 degrees C, and fragmented using
      ultrasound for 10min. The effects of alpha-aminonitriles (1 to 4) over enzymatic
      activities were evaluated using concentrations of 8nM, 2MUM, 8MUM, and 40MUM.
      Results indicated that alpha-aminonitriles caused significant NADH dehydrogenase
      and succinate oxidase inhibition (~44% at the highest concentration tested).
      Succinate dehydrogenase and cytochrome c oxidase activities were found to
      increase (162% and 106% at 40MUM, respectively). It was also observed that these
      compounds produced catalase inhibition and thus prevented H2O2 reduction, which
      induced the formation of reactive oxygen species (ROS). Moreover, NBT assay
      showed that compounds 3 and 4 (with 2-(pyrrolidin-1-yl) acetonitrile as
      substituent) increased by approximately 50% the O2?- concentration in the
      mitochondrial respiratory chain. It was concluded that the tested compounds act
      as complex I inhibitors by blocking electron transport and causing electron leak,
      possibly between complex I and III. Furthermore, alpha-aminonitriles inhibited
      catalase activity; compounds 1 and 2 (with piperidine fragment) inhibited
      glutathione reductase activity and further promoted the accumulation of ROS,
      which probably induced oxidative stress.

PMID- 29463411
TI  - Betanin reduces organophosphate induced cytotoxicity in primary hepatocyte via an
      anti-oxidative and mitochondrial dependent pathway.
AB  - Organophosphates (OP) are potent pesticide commonly utilized in agricultural and
      domestic use. However, plentitude of data represent their side effects in
      different body tissues. We attempted to study whether betanin (a natural pigment)
      is able to mitigate some OPs-induced hepatotoxicity in primary rat hepatocytes.
      Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species
      (ROS) formation, lipid peroxidation (LPO), glutathione (GSH) depletion and
      mitochondrial depolarization were tested as toxicity markers. The outcomes
      revealed that betanin (25MUM) significantly increased cell viability, plummeted
      ROS formation and LPO, restored cellular GSH reservoirs and protected
      mitochondria after chlorpyrifos (CPF) (300MUM), diazinon (DZN) (600MUM) and
      dichlrovos (DDVP) (400MUM) treatment. Taken together, all data suggests the
      potential protective role of betanin in OPs-induced hepatotoxicity in which the
      mechanism appears to be inhibition of ROS formation and mitochondrial protection.

PMID- 29463412
TI  - Omethoate treatment mitigates high salt stress inhibited maize seed germination.
AB  - Omethoate (OM) is a highly toxic organophophate insecticide, which is resistant
      to biodegradation in the environment and is widely used for pest control in
      agriculture. The effect of OM on maize seed germination was evaluated under salt
      stress. Salt (800mM) greatly reduced germination of maize seed and this could be
      reversed by OM. Additionally, H2O2 treatment further improved the effect of OM on
      seed germination. Higher H2O2 content was measured in OM treated seed compared to
      those with salt stress alone. Dimethylthiourea (DTMU), a specific scavenger of
      reactive oxygen species (ROS), inhibited the effect of OM on seed germination, as
      did IMZ (imidazole), an inhibitor of NADPH oxidase. Abscisic acid (ABA) inhibited
      the effect of OM on seed germination, whereas fluridone, a specific inhibitor of
      ABA biosynthesis, enhanced the effect of OM. Taken together, these findings
      suggest a role of ROS and ABA in the promotion of maize seed germination by OM
      under salt stress.

PMID- 29463413
TI  - A genomic approach to identify and monitor a novel pyrethroid resistance mutation
      in the redlegged earth mite, Halotydeus destructor.
AB  - Resistance mechanisms are typically uncovered by identifying sequence variation
      in known candidate genes, however this strategy can be problematic for species
      with no reference data in known relatives. Here we take a genomic approach to
      identify resistance to pyrethroids in the redlegged earth mite, Halotydeus
      destructor, a member of the Penthalidae family of mites that are virtually
      uncharacterized genetically. Based on shallow genome sequencing followed by a
      genome assembly, we first identified contigs of the H. destructor parasodium
      channel gene. By linking variation in this gene to known resistant phenotypes, we
      located a single nucleotide polymorphism in resistant mites. This polymorphism
      results in a leucine (L) to phenylalanine (F) amino acid substitution in the II6
      region (predicted) of the gene (L1024F). This novel mutation has not previously
      been linked to pyrethroid resistance, although other polymorphisms have been
      identified in the two-spotted spider mite, Tetranychus urticae at the same locus
      (L1024V). The sequencing approach was successful in generating a candidate
      polymorphism that was then validated using laboratory bioassays and field
      surveys. A high throughput Illumina-based sequencing diagnostic was developed to
      rapidly assess resistance allele frequencies in pools of mites sourced from
      hundreds of populations across Australia. Resistance was confirmed to be
      widespread in the southern wheatbelt region of Western Australia. Two different
      resistance mutations were identified in field populations, both resulting in the
      same amino acid substitution. The frequency and distribution of resistance
      amplicon haplotypes suggests at least two, and probably more independent origins
      of resistance.

PMID- 29463415
TI  - Endocrinology of prostate cancer.

PMID- 29463414
TI  - Natural meroterpenoids isolated from the plant pathogenic fungus Verticillium
      albo-atrum with noteworthy modification action against voltage-gated sodium
      channels of central neurons of Helicoverpa armigera.
AB  - A new meroterpenoid, named acetoxydehydroaustin A (1) and the known meroterpenoid
      austin (2) were isolated from the plant pathogenic fungus Verticillium albo
      atrum. Their structures were established based on general spectroscopic
      techniques and the relative configuration of compound 1 was determined by single
      crystal X-ray diffraction analysis. We first investigated and identified their
      significant electrophysiological effects on the gating kinetics of voltage-gated
      sodium channels in central neurons acutely dissociated from Helicoverpa armigera
      using whole-cell patch clamp technique. Similar to the effects of pyrethroids on
      sodium late currents, both compounds produced concentration-dependent
      modification of sodium channels, prolonging the kinetics of channel inactivation
      to generate large persistent late currents during depolarization. However,
      different from the effects of tefluthrin and deltamethrin on sodium channels, two
      meroterpenoids did not induce tail currents during deactivation. Compounds 1 and
      2 also caused depolarizing shifts in the voltage dependence of channel
      activation. The V0.5 shifted about 5.02mV and 6.32mV in the depolarizing
      direction by 50MUM 1 and 50MUM 2. The V0.5 of voltage-dependent inactivation
      shifted about 11.42mV and 11.62mV respectively in the hyperpolarizing direction
      by 50MUM 1 and 100MUM 2. In addition, they prolonged the time course of recovery
      from fast-inactivation for sodium channels. The effects of two compounds on the
      voltage-dependent gating substantially increased the size of sodium window
      currents. The overlapped area of window currents increased about 89.69% and
      44.51% respectively by 10MUM compound 1 and 10MUM compound 2. These findings show
      that both compounds have effects on sodium channel activation, inactivation and
      window currents. The voltage-gated sodium channels in central neurons of H.
      armigera are the target sites of two meroterpenoid natural products.

PMID- 29463416
TI  - Irradiation of rainbow trout at early life stages results in a proteomic legacy
      in adult gills. Part A; proteomic responses in the irradiated fish and in non
      irradiated bystander fish.
AB  - Exposure to a single 0.5 Gy X-ray dose of eggs at 48 h after fertilisation (48 h
      egg), eyed eggs, yolk sac larvae (YSL) and first feeders induces a legacy effect
      in adult rainbow trout. This includes the transmission of a bystander effect to
      non-irradiated adult trout which had swam with the irradiated fish. The aim of
      this study was to investigate this legacy by analysing the gill proteome of these
      irradiated and bystander fish. Irradiation at all of the early life stages
      resulted in changes to proteins which play a key role in development but are also
      known to be anti-tumorigenic and anti-oxidant: upregulation of haemoglobin
      subunit beta (48 h egg), haemoglobin, serum albumin 1 precursor (eyed eggs),
      clathrin heavy chain 1 isoform X10 (eyed eggs and first feeders), and actin
      related protein 2/3 complex subunit 4 (first feeders), downregulation of pyruvate
      dehydrogenase, histone 1 (48 h egg), triosephosphate isomerase (TPI), collagen
      alpha-1(1) chain like proteins (YSL), pyruvate kinase PKM-like protein (YSL and
      first feeders), ubiquitin-40S ribosomal proteins S27 and eukaryotic translation
      initiation factor 4 A isoform 1B (first feeders). However irradiation of YSL and
      first feeders (post hatching early life stages) also induced proteomic changes
      which have a complex relationship with tumorigenesis or cancer progression;
      downregulation of alpha-1-antiprotease-like protein precursor, vigilin isoform X2
      and nucleoside diphosphate kinase (YSL) and upregulation of hyperosmotic glycine
      rich protein (first feeders). In bystander fish some proteomic changes were
      similar to those induced by irradiation: upregulation of haemoglobin subunit beta
      (48 h egg), haemoglobin (eyed eggs), actin-related protein 2/3 complex subunit 4,
      hyperosmotic glycine rich protein (first feeders), and downregulation of alpha-1
      antiprotease-like protein, vigilin isoform X2, nucleoside diphosphate kinase
      (YSL), pyruvate kinase PKM-like protein and ubiquitin-40S ribosomal protein S27a
      like (first feeders). Other proteomic changes were unique to bystander fish;
      downregulation of TPI, ubiquitin-40S ribosomal protein S2 (eyed egg), cofilin-2,
      cold-inducible RNA-binding protein B-like isoform X3 (YSL) and superoxide
      dismutase (first feeder), and upregulation of haemoglobin subunit alpha, collagen
      1a1 precursor, apolipoprotein A-1-1 and A-1-2 precursor (first feeders). These
      bystander effect proteomic changes have been shown to be overwhelmingly anti
      tumorigenic or protective of the fish gill.

PMID- 29463417
TI  - MRI as a biomarker for mild neonatal encephalopathy.
AB  - Historically, there has been limited neuro-imaging data acquired on infants with
      mild neonatal encephalopathy (NE). This likely reflects the traditional
      assumption that these infants had a universally good prognosis. As new evidence
      has emerged challenging this assumption, there has been a renewed interest in the
      neuro-imaging findings of these infants. To date, magnetic resonance imaging
      (MRI) studies in infants with mild NE have demonstrated abnormalities in 20-40%
      of cases suggestive that the injury occurs during the peripartum period with a
      predominant watershed pattern of injury. The severity of the injury on MRI in
      infants with mild NE varies, but includes patterns of injury that have been
      associated with long-term neuro-developmental impairment.

PMID- 29463418
TI  - Amount and distribution of benthic marine litter along Sardinian fishing grounds
      (CW Mediterranean Sea).
AB  - Reports of marine litter pollution first appeared in scientific literature of the
      early 1970s; yet, more than 40 years later, no rigorous estimates exist of the
      amount of litter existing in the marine environment. To cope with this global
      urgency, this study reports the status of marine litter abundance along fishing
      grounds surrounding the island of Sardinia (CW Mediterranean Sea; FAO
      Geographical Sub-Area 11) through three years of trawl surveys. A total of 302
      hauls, covering a total of 18.4 km2 of trawled surface were carried out in the
      framework of the MEDITS campaign, at depths comprised between 0 and 800 m. A
      total of 918 items were collected and sorted, with the highest concentration
      observed above 200 m depth. Overall, plastic was the dominant component of
      litter, followed by glass and metal. Comparing our results with other areas from
      the Mediterranean basin, Sardinian waters showed a lower impact, possibly as a
      consequence of multiple factors such as the lower human population density and
      the low flow of the main rivers, among others. In addition, fishermen behaviour
      with respect to marine litter was investigated by mean of anonymous
      questionnaires, emphasizing the necessity to further develop management policies
      and infrastructures supporting litter disposal.

PMID- 29463419
TI  - Influence of the grade on the variability of the mechanical properties of
      polypropylene waste.
AB  - The prior properties of recycled polypropylene depend on the origin of waste
      deposits and its chemical constituents. To obtain specific properties with a
      predefine melt flow index of polypropylene, the suppliers of polymer introduce
      additives and fillers. However, the addition of additives and/or fillers can
      modify strongly the mechanical behaviour of recycled polypropylene. To understand
      the impact of the additives and fillers on the quasi-static mechanical behaviour,
      we consider, in this study, three different recycled polypropylenes with three
      different melt flow index obtained from different waste deposits. The chemical
      constituents of the additives and filler contents of the recycled polypropylenes
      are determined through thermo-physico-chemical analysis. Tensile and bending
      tests performed at different strain rates allow identifying the mechanical
      properties such as the elastic modulus, the yield stress, the maximum stress, and
      the failure mechanisms. The results obtained are compared with non-recycled
      polypropylene and with few researches to explain the combined effect of
      additives. Finally, a post-mortem analysis of the samples was carried out to make
      the link between the obtained mechanical properties and microstructure.

PMID- 29463420
TI  - Comparison of the effectiveness of orthotic intervention, kinesiotaping, and
      paraffin treatments in patients with carpal tunnel syndrome: A single-blind and
      randomized controlled study.
AB  - PURPOSE: The aim of the study was to compare different conservative treatments in
      patients with carpal tunnel syndrome (CTS). STUDY DESIGN: A single-blind
      randomized controlled study. METHODS: Patients (n = 169) diagnosed with mild or
      moderate CTS were screened; 110 met study requirements. The patients were
      randomized into 3 groups. The control (CON) comparison provided to all patients
      was a fabricated night orthotic which held the wrist in a neutral position. The
      second group received adjunctive kinesiotaping (KIN) and the third group received
      paraffin (PARA). All patients were evaluated clinically, electrophysiologically,
      and ultrasonographically before treatment and at 3 weeks, 3 months, and 6 months.
      RESULTS: There were 36 patients in CON, 37 in KIN, and 37 in PARA. Pain reduction
      in KIN was better than the other groups at 3 weeks (mean difference [MD] in CON
      2.4 +/- 2.5, KIN 3.7 +/- 2.0, PARA 2.7 +/- 2.3; P < .01) and 6 months (MD in CON
      3.4 +/- 3.0, KIN 4.9 +/- 3.1, PARA 3.7 +/- 2.9; P < .05). KIN pain reduction was
      better than CON at 3 months (MD in CON 3.8 +/- 2.8, KIN 5.0 +/- 2.5; P < .05).
      Reduction of the cross-sectional area of median nerve at the level of radioulnar
      joint was greater for KIN than CON at 3 weeks (MD in CON 0.0 +/- 0.5, KIN 0.3 +/-
      0.7; P < .01) than PARA at 3 months (MD in KIN 0.3 +/- 0.8, PARA 0.0 +/- 0.8; P <
      .05) and both groups at 6 months (MD in CON 0.1 +/- 0.8, KIN 0.5 +/- 0.9, PARA
      0.0 +/- 1.0 P < .05). CONCLUSION: Adding KIN to night use of an orthotic was more
      effective in achieving symptomatic and structural improvements than either the
      orthotic alone or adjunctive use of paraffin in patients with mild and moderate
      CTS.

PMID- 29463421
TI  - Complications of herpes zoster in immunocompetent older adults: Incidence in
      vaccine and placebo groups in two large phase 3 trials.
AB  - BACKGROUND: An adjuvanted herpes zoster (HZ) subunit vaccine, HZ/su, demonstrated
      high efficacy against HZ and postherpetic neuralgia (PHN) in two randomized,
      observer-blind, placebo-controlled trials in adults aged >=50 and >=70 years (ZOE
      50 and ZOE-70, respectively). METHODS: Data from ZOE-50 and ZOE-70 trials were
      analyzed to evaluate the efficacy of HZ/su against mortality, hospitalizations,
      and non-PHN complications of HZ including HZ-associated vasculitis, stroke, and
      disseminated, ophthalmic, neurologic, and visceral diseases. RESULTS: In the
      pooled ZOE-50/ZOE-70 analysis, 1 of 32 HZ/su recipients (3.1%) and 16 of 477
      placebo recipients (3.4%) with a confirmed HZ episode had complications other
      than PHN. Efficacy against HZ-related complications was 93.7% (95% confidence
      interval, 59.5-99.9%) in adults aged >=50 years and 91.6% (43.3-99.8%) in adults
      >=70 years. Five HZ-related hospitalizations, all in placebo recipients, and no
      HZ-related deaths were reported. CONCLUSIONS: HZ/su reduces the risk of HZ
      associated complications in older adults (NCT01165177; NCT01165229).

PMID- 29463422
TI  - Molecular imaging should have played a role.

PMID- 29463423
TI  - [Is celecoxib a safe alternative for the Fernand Widal syndrome?]
AB  - The Fernand Widal syndrome is a set of associations between asthma, nasal
      polyposis and aspirin sensitivity. Selective cyclo-oxygenase 2 (COX 2) inhibitors
      are recognized as being a therapeutic alternative in cases needing analgesic or
      anti-inflammatory treatment. In a retrospective study, we have compiled data
      concerning oral provocation tests (OPT) undertaken with celecoxib, one of most
      the selective COX 2 inhibitors, in eight patients with the Fernand Widal
      syndrome. They were compared with twenty-seven control patients with sensitivity
      to aspirin or non-steroidal anti-inflammatories, manifesting as asthma, urticaria
      or rhino-conjunctivitis. Four patients with the Fernand Widal syndrome developed
      bronchospasm after taking the usually recommended daily dose of celecoxib while
      all the control patients tolerated it. The Fernand Widal patients who reacted
      during the OPT had a lower threshold of reactivity to aspirin, a more severe
      reaction with aspirin, and/or more severe asthma. In patients with the Fernand
      Widal syndrome, celecoxib is not always a possible alternative to non-steroidal
      anti-inflammatory drugs. Its introduction must be carried out in a hospital
      environment under medical supervision.

PMID- 29463424
TI  - [Invasive pulmonary aspergillosis in an elderly patient with a cerebral abscess
      of odontogenic origin].

PMID- 29463425
TI  - Guidelines of admission, discharge and organization of the pediatric intensive
      care.

PMID- 29463426
TI  - Comparison of two commercial quantitative PCR assays and correlation with the
      first WHO International Standard for human CMV.
AB  - Comparability between CMV assays could be facilitated by the first WHO
      International Standard for human CMV (standard). Standard dilutions were
      submitted to nucleic acid extraction with Versant kPCR Molecular systems SP or
      MagNA Pure LC System followed by the kPCR PLXTM CMV DNA (kPCR) or the CMV R
      geneTM assay (R-gene), respectively; 139 clinical specimens were tested. Both
      assays correlated well with the standard (R2 > 0.96) and a matrix effect was
      observed. Quantitative results correlated reasonably between both assays for
      whole blood (R2 = 0.79) and well for other specimen types (R2 = 0.93).
      Quantification differences were within one log10 of the averaged log10 results
      for 25/27 blood specimens and for 32/33 other specimens. Calibration to the
      standard did not increase this percentage. In conclusion, results of both assays
      showed reasonable correlation with each other and good correlation with the
      standard. Calibration to the standard did not improve comparability of
      quantitative results.

PMID- 29463427
TI  - Chronic diarrhea: A case of Waldenstrom macroglobulinemia.

PMID- 29463428
TI  - Swiss survey on hybrid imaging CTs doses in Nuclear Medicine and proposed
      national dose reference levels.
AB  - A multidisciplinary working group led by the Swiss Federal Office of Public
      Health was formed to plan and perform a nationwide survey of patient radiation
      exposure from computed tomography (CT) in hybrid devices across Nuclear Medicine
      departments. The survey included 16 departments (of which 5 were university
      hospitals) and the submitted responses included 10,673 entries for the 33
      different protocols proposed (11 in PET and 22 in SPECT). The working group
      determined the selection and exclusion criteria applied to the analysis. This
      work presents the survey preparation and data analysis including the exclusion
      criteria used. The results are used to inform recommendations for National
      Diagnostic Reference Levels (DRL) for CT procedures in Nuclear Medicine in
      Switzerland. Of the 33 protocols initially proposed, 10 protocols for both PET
      and SPECT modalities were retained after exclusion criteria and thresholds were
      applied. The results obtained in terms of volume-weighted computed tomography
      dose index (CTDIvol) and dose length product (DLP) have been put forward as
      recommendations for national Diagnostic Reference Levels for protocols in hybrid
      imaging devices in Nuclear Medicine in Switzerland and will be published by the
      Federal Office of Public Health.

PMID- 29463429
TI  - Molecular epidemiology of tuberculosis.
AB  - The application of genotyping tools allowed us to discriminate between the
      Mycobacterium tuberculosis isolates obtained in the laboratory. The
      differentiation between single strains opened the door to molecular epidemiology
      studies, which had helped us to progress in our knowledge of how this pathogen is
      transmitted in the progressively more complex socio-epidemiological scenario. The
      genetic stability of this microorganism led to develop specific methodologies,
      which are thoroughly revised in this chapter. In addition to their application in
      epidemiology, we review, how they can offer a response to different diagnostic
      and clinical challenges. Finally, we focus on describing the novel genomic
      revolution we are experiencing in the analysis of tuberculosis, the methodology
      in which it is based and the novel possibilities it offers, including new routes
      of integrating both the molecular and genomic languages in innovative post
      genomic proposals, better suited to our real-life context.

PMID- 29463430
TI  - The post-truth behind the asthma-COPD overlap and the orbit of Mercury: lessons
      from the CHACOS study.

PMID- 29463431
TI  - Interfering with Kupffer cell replenishment: New insights into liver injury.

PMID- 29463432
TI  - A GIS-based tool for an integrated assessment of spatial planning trade-offs with
      aquaculture.
AB  - The increasing demand for protein from aquaculture will trigger a global
      expansion of the sector in coastal and offshore waters. While contributing to
      food security, potential conflicts with other traditional activities such as
      fisheries or tourism are inevitable, thus calling for decision-support tools to
      assess aquaculture planning scenarios in a multi-use context. Here we introduce
      the AquaSpace tool, one of the first Geographic Information System (GIS)-based
      planning tools empowering an integrated assessment and mapping of 30 indicators
      reflecting economic, environmental, inter-sectorial and socio-cultural risks and
      opportunities for proposed aquaculture systems in a marine environment. A bottom
      up process consulting more than 350 stakeholders from 10 countries across
      southern and northern Europe enabled the direct consideration of stakeholder
      needs when developing the GIS AddIn. The AquaSpace tool is an open source product
      and builds in the prospective use of open source datasets at a European scale,
      hence aiming to improve reproducibility and collaboration in aquaculture science
      and research. Tool outputs comprise detailed reports and graphics allowing key
      stakeholders such as planners or licensing authorities to evaluate and
      communicate alternative planning scenarios and to take more informed decisions.
      With the help of the German North Sea case study we demonstrate here the tool
      application at multiple spatial scales with different aquaculture systems and
      under a range of space-related development constraints. The computation of these
      aquaculture planning scenarios and the assessment of their trade-offs showed that
      it is entirely possible to identify aquaculture sites, that correspondent to
      multifarious potential challenges, for instance by a low conflict potential, a
      low risk of disease spread, a comparable high economic profit and a low impact on
      touristic attractions. We believe that a transparent visualisation of risks and
      opportunities of aquaculture planning scenarios helps an effective Marine Spatial
      Planning (MSP) process, supports the licensing process and simplifies
      investments.

PMID- 29463433
TI  - Carbon-ion radiotherapy for locoregional recurrence after primary surgery for
      pancreatic cancer.
AB  - The efficacy and safety of carbon ion radiotherapy (C-ion RT) for locoregional
      recurrence after surgery for pancreatic cancer were retrospectively evaluated.
      The results for 30 patients showed that C-ion RT was performed safely with
      relatively long overall survival, good local control, and minimal toxicity.

PMID- 29463434
TI  - Molecular Subtypes of Clear-cell Renal Cell Carcinoma are Prognostic for Outcome
      After Complete Metastasectomy.
AB  - BACKGROUND: Metastasectomy is routinely performed in selected patients with
      metastatic clear-cell renal cell carcinoma (ccRCC) as an alternative to systemic
      therapy. In the absence of randomized trials, the benefit and best way of patient
      selection remain unclear. Earlier, we described four molecular ccRCC-subtypes
      (ccrcc1-4) that have a prognostic and predictive value upon first-line sunitinib
      or pazopanib. OBJECTIVE: Assess the prognostic value of ccrcc1-4 subtypes after
      complete metastasectomy. (1) Compare outcomes of good-prognosis ccrccc2&3-tumors
      with intermediate/poor-prognosis ccrcc1&4-tumors. (2) Compare outcomes of the
      four subtypes separately. DESIGN, SETTING, AND PARTICIPANTS: Single-center
      retrospective study (1995-2017), assessing 43 ccRCC patients undergoing complete
      metastasectomy without systemic treatment. INTERVENTION: Molecular subtype
      determined with established 35-gene expression classifier. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: Median disease-free survival (DFS), time to systemic
      therapy, cancer-specific (CSS) and overall survival (OS) from metastasectomy,
      estimated with Kaplan-Meier method and tested against other predictors with
      multivariable Cox regression. RESULTS AND LIMITATIONS: Median DFS was 23 mo for
      ccrcc2&3-tumors versus 9 mo for ccrcc1&4-tumors (p=0.011, hazard ratio [HR]=2.6).
      Median time to systemic therapy was 92 mo versus 28 mo (p=0.003, HR=3.3). Median
      CSS was 133 mo versus 50 mo (p<0.001, HR=2.7). Median OS was 127 mo versus 50 mo
      (p=0.011, HR=2.5). The classification remained independent upon multivariable
      analysis. Outcomes remained significantly different when comparing four subtypes
      separately. The intrinsic heterogeneity of expression profiles is a limitation of
      this approach. CONCLUSION: Even after clinical patient selection, patients with a
      ccrcc1- or ccrcc4-tumor are at a higher risk of relapse after complete
      metastasectomy. Patients with a ccrcc2- or ccrcc3-tumor usually experience a long
      DFS. These results need validation in a larger cohort to establish the subtypes
      as prognostic marker. PATIENT SUMMARY: Metastasectomy is recommended for some
      patients with metastatic clear-cell kidney cancer; however, we do not know who
      will benefit the most. We show that molecular subtypes increase the possibility
      to predict which patients are at risk for early relapse after metastasectomy and
      who may benefit more from other treatment options.

PMID- 29463435
TI  - Re: Jochen Walz. The "PROMIS" of Magnetic Resonance Imaging Cost Effectiveness in
      Prostate Cancer Diagnosis? Eur Urol 2018;73:31-2.

PMID- 29463436
TI  - What is the Impact of Smoking on Revision Total Hip Arthroplasty?
AB  - BACKGROUND: There is a paucity of literature evaluating the impact of smoking on
      revision total hip arthroplasty (THA) outcomes. The purpose of this study was to
      identify the effect of smoking on complications after revision THA. METHODS: We
      queried the American College of Surgeons National Surgical Quality Improvement
      Program database to identify patients who underwent revision THA between 2006 and
      2014. Patients were divided into current smokers and nonsmokers. Each cohort was
      compared in terms of demographics, preoperative comorbidities, and operative
      time. Multivariate logistic regression analysis was utilized. Adjusted odds
      ratios (OR) for the outcomes of any wound complication, deep infection, and
      reoperation within 30 days of revision THA were calculated. RESULTS: In total,
      8237 patients had undergone a revision THA. Of these patients, 14.7% were current
      smokers and 85.3% were nonsmokers. Univariate analyses demonstrated that smokers
      had a higher rate of any wound complication (4.1% vs 3.0%, P = .04), deep
      infection (3.2% vs 1.9%, P = .003), and reoperation (6.8% vs 4.8%, P = .003).
      Multivariate analysis controlling for confounding demographic, comorbidity, and
      operative variables identified current smokers as having a significantly
      increased risk of deep infection (OR, 1.58; 95% CI, 1.04-2.38) and reoperation
      (OR, 1.37; 95% CI, 1.03-1.85). CONCLUSION: Smoking significantly increases the
      risk of infection and reoperation after revision THA. The results are even more
      magnified for revision procedures compared to published effects of smoking on
      primary THA complications. Further research is needed regarding the impact of
      smoking cessation on mitigation of these observed risks.

PMID- 29463437
TI  - Prehospital quick sequential organ failure assessment as a tool to predict in
      hospital mortality.
AB  - OBJECTIVE: This study aimed to evaluate the predictive ability of quick
      sequential organ failure assessment (qSOFA) score for in-hospital mortality among
      patients transported by physician-staffed helicopters. METHODS: We conducted a
      single-center, retrospective observational study using the physician-staffed
      helicopter registry data between 2003 and 2016. We calculated the qSOFA scores
      based on the patients' vital signs, which were measured on the scene. The tool's
      discriminatory ability was determined using the area under the curve of the
      receiver operating characteristic. RESULTS: A total of 1849 patients with a mean
      age of 63.0 (standard deviation [SD], 18.4) years were included in this study.
      The diagnostic categories included were trauma and nontrauma cases (1038 [56%]
      and 811 [44%], respectively). In-hospital mortality was documented in 169 (9%)
      patients. Meanwhile, the in-hospital mortality rates among patients with qSOFA
      scores of 0, 1, 2, and 3 were 5/411 (1%), 69/797 (9%), 71/541 (13%), and 24/100
      (24%), respectively (P<0.0001 for trend). If the cutoff point is >=1, the
      sensitivity and specificity of the qSOFA scores were 0.97 and 0.24, respectively.
      The area under the curve of the qSOFA scores was 0.67 for all patients, whereas
      that for trauma patients was 0.75. CONCLUSION: An increase in the qSOFA score is
      associated with a gradual increase in the in-hospital mortality rate among all
      patients. In particular, a very low mortality rate was observed among patients
      with a qSOFA score of 0. The qSOFA score predicted the in-hospital mortality of
      patients with trauma well.

PMID- 29463438
TI  - Intubation of prehospital patients with curved laryngoscope blade is more
      successful than with straight blade.
AB  - OBJECTIVE: Direct laryngoscopy can be performed using curved or straight blades,
      and providers usually choose the blade they are most comfortable with. However,
      curved blades are anecdotally thought of as easier to use than straight blades.
      We seek to compare intubation success rates of paramedics using curved versus
      straight blades. METHODS: Design: retrospective chart review. SETTING: hospital
      based suburban ALS service with 20,000 annual calls. SUBJECTS: prehospital
      patients with any direct laryngoscopy intubation attempt over almost 9years.
      First attempt and overall success rates were calculated for attempts with curved
      and straight blades. Differences between the groups were calculated. RESULTS:
      2299 patients were intubated by direct laryngoscopy. 1865 had attempts with a
      curved blade, 367 had attempts with a straight blade, and 67 had attempts with
      both. Baseline characteristics were similar between groups. First attempt success
      was 86% with a curved blade and 73% with a straight blade: a difference of 13%
      (95% CI: 9-17). Overall success was 96% with a curved blade and 81% with a
      straight blade: a difference of 15% (95% CI: 12-18). There was an average of 1.11
      intubation attempts per patient with a curved blade and 1.13 attempts per patient
      with a straight blade (2% difference, 95% CI: -3-7). CONCLUSIONS: Our study found
      a significant difference in intubation success rates between laryngoscope blade
      types. Curved blades had higher first attempt and overall success rates when
      compared to straight blades. Paramedics should consider selecting a curved blade
      as their tool of choice to potentially improve intubation success.

PMID- 29463439
TI  - BCG-Induced Granulomatous Balanoposthitis and Lymphadenitis Unresponsive to
      Isoniazid Therapy: A Case Report and Review of the Literature.

PMID- 29463440
TI  - Post-SSRI Sexual Dysfunction: Preclinical to Clinical. Is It Fact or Fiction?
AB  - INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are a widely used
      class of drug for various psychiatric disorders during the lifespan, including
      pregnancy, lactation, childhood, and adolescence. Deterioration in sexual
      functioning is a major and serious adverse effect of SSRIs. There is emerging
      evidence that SSRIs can have long-lasting effects on sexuality. AIM: To summarize
      the long-lasting effects of SSRIs on sexuality, starting with animal models and
      continuing with the clinical experience of different investigators. METHOD: A
      literature review of relevant publications in PubMed. MAIN OUTCOME MEASURES: To
      assess the long-lasting effects of SSRIs on sexuality. RESULTS: Although the
      persistent effects of SSRIs on sexuality have been little studied in humans,
      animal studies suggest that SSRIs might cause permanent sexual dysfunction after
      ending SSRI exposure at a young age but not in adulthood in rats. There are no
      prospective randomized controlled trials in humans and the present evidence is
      derived from case reports, incidental research findings, and experiences of some
      internet communities. CONCLUSION: There is some preclinical evidence from animal
      studies for enduring SSRI-induced sexual dysfunction, but the available clinical
      information could prevent a clear decision about the existence of post-SSRI
      sexual dysfunction, its pathophysiology, and its management. We need more
      research to fill in the gaps in our knowledge. Coskuner ER, Culha MG, Ozkan B,
      Kaleagasi EO. Post-SSRI Sexual Dysfunction: Preclinical to Clinical. Is It Fact
      or Fiction? Sex Med Rev 2018;6:217-223.

PMID- 29463441
TI  - Perineal Ultrasound: a Review in the Context of Ejaculatory Dysfunction.
AB  - BACKGROUND: Ejaculation consists of the emission of semen from seminal vesicles
      and prostate, followed by expulsion. Ejaculatory dysfunction may take several
      forms including premature ejaculation, delayed or anejaculation, retrograde
      ejaculation, and painful ejaculation. Ejaculation is what we can see whereas
      orgasm is what we feel. The presence of ejaculate does not indicate the ability
      to experience orgasm. Hence, for the purpose of this work we consider orgasm and
      ejaculation as 2 separate neurobiological phenomena. AIM: To review the role of
      advanced investigative techniques such as perineal ultrasound in the diagnosis
      and management of ejaculation and ejaculatory dysfunction. METHODS: We performed
      a PubMed search for key words individually and in combination: "ejaculation,"
      "ejaculatory dysfunction," "delayed ejaculation," "painful ejaculation,"
      "retrograde ejaculation," "perineal ultrasound," and "transrectal ultrasound." We
      also share our local experience using perineal ultrasound in assessing
      ejaculation. OUTCOMES: Perineal ultrasound can be used as an aid in the
      investigation of ejaculatory dysfunction. RESULTS: Evaluation of ejaculatory
      function hinges on a detailed psychosexual history and appropriate physical
      examination. Function of the ejaculatory center in the spine is androgen
      dependent; thus, hormonal evaluation is an important aspect of the workup.
      Disorders of ejaculation and orgasm require evaluation of neuromuscular reflexes
      activated during sexual activity. Dynamic ultrasonographic (US) ejaculatory
      orgasmic studies allow for reproducible and detailed descriptions of the sexual
      response. Transrectal ejaculatory studies are useful in uncovering reasons for
      lack of antegrade semen emission, especially in men with poor sperm production or
      after vasectomy. Dynamic US studies contribute clinical utility in its non
      invasive nature and can provide insight to the dynamic processes surrounding
      pelvic floor functioning in men. CONCLUSIONS: Perineal US for men with delayed
      ejaculation or anejaculation, painful ejaculation, or retrograde ejaculation may
      be helpful in select cases. Further research using this modality may help advance
      our understanding of ejaculatory dysfunction. Forbes CM, Flannigan R, Paduch DA.
      Perineal Ultrasound: a Review in the Context of Ejaculatory Dysfunction. Sex Med
      Rev 2018;6:419-428.

PMID- 29463442
TI  - [Perception of Primary Care physicians on the integration with cardiology through
      continuity of healthcare programs in secondary prevention].
AB  - OBJECTIVE: To determine the perception of Primary Care (PC) physicians on the
      integration with cardiology (CA) through continuity of healthcare programs.
      MATERIAL AND METHODS: A cross-sectional and multicentre study was conducted, in
      which a total of 200 PC physicians from all over Spain completed a qualitative
      survey that evaluated the level of integration with CA in secondary prevention.
      Physicians were grouped according to the level of PC-CA integration. RESULTS: The
      integration between CA and PC was good, but it was better in those centres with a
      higher integration (74.0% vs. 60.0%; p=.02) and in general, physicians considered
      that integration had improved (92.0% vs. 73.0%; p<.001). Almost all PC physicians
      received the hospital discharge report. The majority of the hospital discharge
      reports included recommendations about the CA and PC follow-up, control of risk
      factors, as well as the duration of secondary prevention treatment, with not
      significant differences according to the level of integration. In 55.8%, 63.6%,
      and 51.3% of hospital discharge reports, indications were given on when to
      perform the follow-up blood analysis, as well as information about returning to
      working life and sexual activity, respectively. The most common communication
      method was the paper-based report (75 vs. 84%; p=NS). The communication between
      healthcare levels was greater in those Primary Care centres with a higher level
      of integration, as well as periodicity of the communication and the satisfaction
      of physicians (80.0% vs. 63.0%; p=.005). CONCLUSIONS: The level of integration
      between PC and CA is, in general, satisfactory, but those centres with a higher
      level of integration benefit more from a greater communication and satisfaction.

PMID- 29463443
TI  - BRexit: Possible Brassinosteroid Export and Transport Routes.
AB  - The movement and differential distribution of endogenous plant hormones are the
      determining factors for many developmental processes. Brassinosteroids (BRs) are
      a group of plant steroidal hormones that promote growth and development. Although
      synthesis and signalling of BRs are well described and characterized, the exit
      mechanism of these compounds from the cell remains uncharacterizd. Whether BRs
      are able to move within the apoplast and whether the BR synthesis in one cell can
      trigger the signalling in its neighbours is also unknown. Here, we draw the
      attention to these aspects of the BR biology, propose several BR cell export
      routes and discuss possible consequences of local BR hormonal gradients,
      resulting from localized biosynthesis and a short-distance transport, for plant
      development.

PMID- 29463444
TI  - Anodal Transcranial Direct Current Stimulation of the motor cortex reduces
      chronic pain in Alcock canal syndrome.

PMID- 29463445
TI  - Pyle's Disease: A Human Model of Differentiated Cortical and Trabecular
      Homeostasis.
AB  - Pyle's disease (OMIN number 265900) is a metaphyseal dysplasia of benign course,
      inherited with an autosomal recessive pattern. Some 30 genuine cases have been
      described so far. The cause of this process has been known since 2016, when its
      relationship to mutations in the gene encoding the sFRP protein, a known
      inhibitor of the Wnt pathway, was discovered. We report the case of a 58-year-old
      man, diagnosed with Pyle's disease based on his clinical and radiographic
      characteristics, whose phenotype suggested a differential control of cortical and
      trabecular bone homeostasis.

PMID- 29463446
TI  - How to treat chronic myeloid leukemia (CML) in older adults.
AB  - Chronic myeloid leukemia (CML), a myeloproliferative neoplasm defined by the
      t(9;22)(q34;q11) chromosomal translocation, primarily affects older adults.
      Historically, effective treatment options were not available for older CML
      patients ineligible for curative allogeneic stem cell transplant, and the disease
      was therefore usually fatal within several years of diagnosis. The development of
      tyrosine kinase inhibitors (TKIs) that effectively target the constitutively
      active mutant tyrosine kinase in CML has dramatically improved outcomes for all
      patients with CML, including older patients. While older patients were
      underrepresented in prospective trials, TKI therapy can be successfully
      administered to older adults with CML with excellent efficacy and proven
      tolerability. TKI selection and monitoring for adverse events should be tailored
      based on co-morbidities. As with younger patients, life expectancy of older
      adults with CML now approaches that of age-matched controls. Here we review
      guidelines for management of older adults with CML.

PMID- 29463447
TI  - Novel inhibitors of Staphylococcus aureus RnpA that synergize with mupirocin.
AB  - We recently discovered RnpA as a promising new drug discovery target for
      methicillin-resistant S. aureus (MRSA). RnpA is an essential protein that is
      thought to perform two required cellular processes. As part of the RNA degrasome
      Rnpa mediates RNA degradation. In combination with rnpB it forms RNase P
      haloenzymes which are required for tRNA maturation. A high throughput screen
      identified RNPA2000 as an inhibitor of both RnpA-associated activities that
      displayed antibacterial activity against clinically relevant strains of S.
      aureus, including MRSA. Structure-activity studies aimed at improving potency and
      replacing the potentially metabotoxic furan moiety led to the identification of a
      number of more potent analogs. Many of these new analogs possessed overt cellular
      toxicity that precluded their use as antibiotics but two derivatives, including
      compound 5o, displayed an impressive synergy with mupirocin, an antibiotic used
      for decolonizing MSRA whose effectiveness has recently been jeopardized by
      bacterial resistance. Based on our results, compounds like 5o may ultimately find
      use in resensitizing mupirocin-resistant bacteria to mupirocin.

PMID- 29463448
TI  - Discovery and validation of 2-styryl substituted benzoxazin-4-ones as a novel
      scaffold for rhomboid protease inhibitors.
AB  - Rhomboids are intramembrane serine proteases with diverse physiological functions
      in organisms ranging from archaea to humans. Crystal structure analysis has
      provided a detailed understanding of the catalytic mechanism, and rhomboids have
      been implicated in various disease contexts. Unfortunately, the design of
      specific rhomboid inhibitors has lagged behind, and previously described small
      molecule inhibitors displayed insufficient potency and/or selectivity. Using a
      computer-aided approach, we focused on the discovery of novel scaffolds with
      reduced liabilities and the possibility for broad structural variations. Docking
      studies with the E. coli rhomboid GlpG indicated that 2-styryl substituted
      benzoxazinones might comprise novel rhomboid inhibitors. Protease in vitro assays
      confirmed activity of 2-styryl substituted benzoxazinones against GlpG but not
      against the soluble serine protease alpha-chymotrypsin. Furthermore, mass
      spectrometry analysis demonstrated covalent modification of the catalytic residue
      Ser201, corroborating the predicted mechanism of inhibition and the formation of
      an acyl enzyme intermediate. In conclusion, 2-styryl substituted benzoxazinones
      are a novel rhomboid inhibitor scaffold with ample opportunity for optimization.

PMID- 29463449
TI  - Collaborative opportunities for psychiatric trainees and young psychiatrists in
      Europe: the Early Career Psychiatrists Committee of the European Psychiatric
      Association.

PMID- 29463450
TI  - Glucagon-like Peptide-1 Receptor Agonists and Cardiovascular Events: Class
      Effects versus Individual Patterns.
AB  - Several new glucose-lowering medications have been approved, such as dipeptidyl
      peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and
      sodium glucose cotransporter-2 inhibitors. Among GLP-1RAs, lixisenatide, a short
      acting drug, did not show cardiovascular (CV) benefits in patients with Type 2
      diabetes mellitus (T2D) and acute coronary syndrome. Extended-release exenatide
      was also not significantly better for CV outcomes. By contrast, once daily
      liraglutide and once weekly semaglutide, both long-acting GLP-1RAs, decreased the
      incidence of major adverse CV events and mortality. This Review attempts to
      explain favorable CV results with some, but not all, GLP-1RAs, to aid in their
      differential prescription with the aim of further reducing the adverse CV burden
      of T2D.

PMID- 29463451
TI  - Starvation, Stress Resistance, and Cancer.
AB  - Cancer cells are characterized by dysregulation in signal transduction and
      metabolic pathways leading to increased glucose uptake, altered mitochondrial
      function, and the evasion of antigrowth signals. Fasting and fasting-mimicking
      diets (FMDs) provide a particularly promising intervention to promote
      differential effects in normal and malignant cells. These effects are caused in
      part by the reduction in IGF-1, insulin, and glucose and the increase in IGFBP1
      and ketone bodies, which generate conditions that force cancer cells to rely more
      on metabolites and factors that are limited in the blood, thus resulting in cell
      death. Here we discuss the cellular and animal experiments demonstrating the
      differential effects of fasting on normal and cancer cells and the mechanisms
      responsible for these effects.

PMID- 29463452
TI  - [Asymmetries in the hospital treatment of acute ischemic stroke].
AB  - OBJECTIVE: To analyze the degree of implementation of the protocolized care for
      acute stroke in the Spanish emergency departments and to discuss the territorial
      differences in the treatment of stroke. MATERIAL AND METHODS: Multicenter
      national survey conducted to evaluate the current treatment of ischemic stroke in
      emergency departments. The main variables analyzed were focused at evaluating the
      participation of ERs in the performance of thrombolysis, interventional treatment
      and destination of patients with stroke. RESULTS: 42 emergency services
      participated. 90.5% have stroke protocol. In 52.4% is identified an emergency
      physician referent in cerebrovascular pathology. In 2016 2090 thrombolysis were
      performed, we observe a great variability in the number of treatments per
      hospital [0-222]. 11.9% were admitted in the Observation area. Only one-third of
      the hospitals currently treat stroke with thrombectomy. 31% have a telemedicine
      service available. CONCLUSIONS: Urgencies plays a fundamental role in the chain
      of care of stroke treatment. There is a worrying variability between centers in
      the management of the stroke.

PMID- 29463453
TI  - [Supply medicinal products improvement in outpatient care in a hospital pharmacy
      service].
AB  - INTRODUCTION: Pharmaceutical care to outpatients is currently one of the main
      occupations of hospital pharmacy services (PEX). There are several questionnaires
      to measure the satisfaction of the PEX of a pharmacy service, and the results of
      these questionnaires can generate improvement actions that result in
      satisfaction. OBJECTIVES: To verify if a satisfaction questionnaire for
      outpatients is valid for the generation of improvements in the care provided, and
      if after its implementation, the same questionnaire is able to detect changes in
      satisfaction. MATERIAL AND METHOD: Prospective study of a single center carried
      out in a tertiary hospital in 2015 and 2016. A questionnaire previously validated
      with 16 Likert-type items was used. Demographic and classification data were
      collected. A descriptive analysis was performed and the internal consistency was
      calculated using the Cronbach's alpha value. RESULTS: A total of 258
      questionnaires were collected in 2015 and 493 in 2016. There were no differences
      in the baseline characteristics of the patients and users of the service. The
      items with the lowest satisfaction scores in 2015 (comfort of the waiting room,
      dispensing privacy, drug pick-up time and medication pick-up time) guided the
      improvement actions to be implemented. In 2016 there was an improvement in the
      waiting time until collection in 12.3% (p = 0.002); in the comfort of the waiting
      room 4.9% (p = 0.304); business hours for medication collection, 10.7% (p =
      0.013); and in the confidentiality of the dispensation 4% (p = 0.292). The
      remaining scores fluctuated minimally, with no statistical significance at all. A
      5.1% improvement in overall satisfaction was found (p < 0.001). Satisfaction
      values obtained as a whole were high. CONCLUSIONS: The satisfaction questionnaire
      is a valid instrument for generating actions to improve the care received in an
      outpatient unit of a pharmacy service. This same questionnaire is a tool to
      monitor the changes implemented to improve the care received.

PMID- 29463454
TI  - Diagnostic potential of dentatorubrothalamic tract analysis in progressive
      supranuclear palsy.
AB  - BACKGROUND: The differentiation of progressive supranuclear palsy-parkinsonism
      (PSP-P) from Parkinson's disease (PD) remains a major clinical challenge.
      OBJECTIVES: To evaluate the diagnostic potential of observer-independent
      assessments of microstructural integrity within infratentorial brain regions to
      differentiate PSP-Richardson's syndrome (PSP-RS), PSP-P and PD. METHODS: 3T MRI
      parameters of mean diffusivity, fractional anisotropy, grey and white matter
      volumes from patients with PSP-RS (n = 12), PSP-P (n = 12) and mean disease
      duration of 2.4 +/- 1.7 years were compared with PD patients (n = 20) and healthy
      controls (n = 23) by using statistical parametric mapping and the spatially
      unbiased infratentorial template. Subsequently MRI measurements of the
      dentatorubrothalamic tract were determined observer-independently by a validated
      probabilistic infratentorial atlas. The impairment of gait and postural stability
      was evaluated by a sum-score derived from the Unified Parkinson Disease Rating
      Scale. RESULTS: Significant mean diffusivity increases, fractional anisotropy
      decreases and corresponding volume loss were localized in mesencephalic
      tegmentum, superior cerebellar peduncle, decussation of superior cerebellar
      peduncle and dentate nucleus in PSP-RS and PSP-P compared to PD and healthy
      controls. Altered microstructural integrity of the dentatorubrothalamic tract in
      PSP-RS was significantly more pronounced compared to PSP-P and correlated
      significantly with the gait and postural stability sum-score. Linear discriminant
      analysis identified diffusion tensor imaging measures of the dentatorubrothalamic
      tract and the gait and postural stability sum-score to classify correctly 95.5%
      of PRP-RS, PSP-P and PD patients. CONCLUSIONS: Observer-independent analysis of
      microstructural integrity within the dentatorubrothalamic tract in combination
      with assessments of gait and postural stability differentiate PSP-P from PSP-RS
      and PD in early to moderately advanced stages.

PMID- 29463455
TI  - Prognosis of hospitalized patients with community-acquired pneumonia.
AB  - INTRODUCTION: The long-term prognosis of patients with community-acquired
      pneumonia (CAP) has attracted increasing interest in recent years. The objective
      of the present study is to investigate the short and long-term outcomes in
      hospitalized patients with CAP and to identify the predictive factors associated
      with mortality. PATIENTS AND METHODS: The study was designed as a retrospective,
      multicenter, observational study. Hospitalized patients with CAP, as recorded in
      the pneumonia database of the Turkish Thoracic Society between 2011 and 2013,
      were included. Short-term mortality was defined as 30-day mortality and long-term
      mortality was assessed from those who survived 30 days. Predictive factors for
      short- and long-term mortality were analyzed. RESULTS: The study included 785
      patients, 68% of whom were male and the mean age was 67+/-16 (18-92). The median
      duration of follow-up was 61.2+/-11.8 (37-90) months. Thirty-day mortality was
      9.2% and the median survival of patients surviving 30 days was 62.8+/-4.4 months.
      Multivariate analysis revealed that advanced age, the absence of fever, a higher
      Charlson comorbidity score, higher blood urea nitrogen (BUN)/albumin ratios and
      lower alanine aminotransferase (ALT) levels were all predictors of long-term
      mortality. CONCLUSION: Long-term mortality following hospitalization for CAP is
      high. Charlson score and lack of fever are potential indicators for decreased
      long-term survival. As novel parameters, baseline BUN/albumin ratios and ALT
      levels are significantly associated with late mortality. Further interventions
      and closer monitoring are necessary for such subgroups of patients.

PMID- 29463456
TI  - Traumatic life event exposure and psychotic-like experiences: A multiple
      mediation model of cognitive-based mechanisms.
AB  - Several cognitive mechanisms have been proposed to account for the relationship
      between exposure to traumatic life events (TLEs) and the entire psychosis
      spectrum. However, only few of these mechanisms have been empirically tested and
      those that have been tested have not considered multiple mechanisms
      simultaneously. The purpose of this study was to examine whether perceived
      stress, dissociation, negative self-schemas, negative other-schemas, and/or
      external locus of control mediated the association between TLEs and psychotic
      like experiences (PLEs). An undergraduate sample of 945 individuals completed a
      battery of self-report questionnaires. We found significant indirect effects from
      TLE exposure to PLEs through perceived stress, dissociation, external locus of
      control, negative self-schemas, and negative other-schemas. When controlling for
      comorbid psychological symptoms, only the indirect effect from TLE exposure to
      PLEs through dissociation continued to be significant. Targeting stress
      sensitivity, maladaptive schemas, dissociative tendencies, and externalizing
      attributional styles may prove useful in the amelioration of risk for various
      psychopathologies (e.g., mood, psychosis) in the aftermath of TLE exposure.
      Findings underscore the importance of targeting trauma-related cognitions in the
      prevention or reduction of psychotic-like experiences or disorders.

PMID- 29463457
TI  - Clinical trajectories in the ultra-high risk for psychosis population.
AB  - BACKGROUND: Traditionally, research in the ultra-high risk (UHR) for psychosis
      population has focused on the treatment of existing symptomatology and prevention
      of transition to psychosis. Recently, there has been an increase in focus on
      outcomes in individuals who do not transition to psychosis. However, there is a
      lack of standardised definitions of remission, recovery, recurrence and relapse
      in UHR, resulting in the inability to generalise and replicate outcomes. METHOD:
      The aims of the current study were to develop definitions for remission,
      recovery, recurrence and relapse, and apply them to a UHR cohort allowing the
      identification of longitudinal clinical trajectories. Further stratification in
      broader categories of favourable and unfavourable outcomes was applied. The
      predictive value of various baseline factors on specific clinical trajectories
      was also assessed. RESULTS: 17 different trajectories were identified in a cohort
      of 202 individuals within a 12-month period and classified according to the
      suggested definitions for recovery (35.7%), remission (7.5%), any recurrence
      (20%), no remission (17.3%), relapse (4.0%) and transition to psychosis (15.8%).
      Favourable and unfavourable trajectories represented 43.2% and 57.1%
      respectively. Long duration of untreated symptoms and high depression scores were
      associated with unfavourable outcomes. DISCUSSION: It is possible to apply clear
      definitions of remission, recovery, recurrence, relapse and transition to
      psychosis to a UHR cohort to evaluate longitudinal clinical trajectories.
      Acceptance and use of these definitions will help to facilitate comparisons
      between trials and to improve clinical clarity across the range of available
      therapeutic options in UHR individuals.

PMID- 29463458
TI  - Surgical treatment by percutaneous anterior screw fixation of scaphoid fractures.
AB  - The aim of this study was to evaluate the results of percutaneous screw fixation
      of scaphoid waist fractures in our surgery unit by comparing them with recent
      data from the literature. This was a retrospective, descriptive study conducted
      between January 2010 and September 2016. Patients operated due to a recent
      scaphoid fracture and treated by percutaneous anterograde screw fixation with a
      Herbert screw were included in this study. Our cohort was a sub-set from a
      scaphoid fracture group; other fracture sites, other treatment techniques and
      fractures associated with scapholunate ligament lesions were excluded. The time
      to union and union rate were recorded. The Youm and McMurtry indices, scaphoid
      and scapholunate angles were measured on radiographs. A total of 21 patients were
      included. The mean age was 30 years (18-44) and the sex ratio (male/female) was
      9.5. The union rate was 95% with an average follow-up of 24 months. Four patients
      had a mobility deficit in the sagittal plane of about 9 degrees . No malunion was
      found, and no major complications were observed. Based on this study,
      percutaneous fixation of the scaphoid with Herbert's screw is a reliable
      technique that leads to union in most cases with limited postoperative
      immobilization.

PMID- 29463459
TI  - Intraoperative cone beam computed tomography-guided endovascular recanalization
      of an interrupted aorta.
AB  - A 42-year-old man sustained a stroke secondary to malignant hypertension and was
      found to have complete aortic interruption. We report a case of real-time image
      guided endovascular repair to highlight the value of preprocedural planning and
      intraprocedural cone beam computed tomography. Two-dimensional fluoroscopy
      enhanced with three-dimensional landmarks from cone beam computed tomography was
      used to direct a Nykanen radiofrequency wire (Baylis Medical, Montreal, Quebec,
      Canada) through the interruption, avoiding critical adjacent structures. A
      covered Cheatham-Platinum stent (NuMED, Inc, Hopkinton, NY) was deployed
      successfully, recanalizing the thoracic aorta. The pressure gradient normalized,
      and the patient was discharged on postoperative day 1. At 10-month follow-up, the
      patient was on an antihypertensive regimen of two minimum-dose drugs.

PMID- 29463460
TI  - Empowerment and involvement.

PMID- 29463461
TI  - Aromatherapy Versus Oral Ondansetron for Antiemetic Therapy Among Adult Emergency
      Department Patients: A Randomized Controlled Trial.
AB  - STUDY OBJECTIVE: We compare aromatherapy with inhaled isopropyl alcohol versus
      oral ondansetron for treating nausea among emergency department (ED) patients not
      requiring immediate intravenous access. METHODS: In a randomized, blinded,
      placebo-controlled trial, we enrolled a convenience sample of adults presenting
      to an urban tertiary care ED with chief complaints including nausea or vomiting.
      We randomized subjects to 1 of 3 arms: inhaled isopropyl alcohol and 4 mg oral
      ondansetron, inhaled isopropyl alcohol and oral placebo, and inhaled saline
      solution placebo and 4 mg oral ondansetron. The primary outcome was mean nausea
      reduction measured by a 0- to 100-mm visual analog scale from enrollment to 30
      minutes postintervention. Secondary outcomes included receipt of rescue
      antiemetic medications and adverse events. RESULTS: We enrolled 122 subjects, of
      whom 120 (98.3%) completed the study. Of randomized subjects, 40 received inhaled
      isopropyl alcohol and oral ondansetron, 41 received inhaled isopropyl alcohol and
      oral placebo, and 41 received inhaled saline solution placebo and oral
      ondansetron. The mean decrease in nausea visual analog scale score in each arm
      was 30 mm (95% confidence interval [CI] 22 to 37 mm), 32 mm (95% CI 25 to 39 mm),
      and 9 mm (95% CI 5 to 14 mm), respectively. The proportions of subjects who
      received rescue antiemetic therapy in each arm were 27.5% (95% CI 14.6% to
      43.9%), 25.0% (95% CI 12.7% to 41.2%), and 45.0% (95% CI 29.3% to 61.5%),
      respectively. There were no adverse events. CONCLUSION: Among ED patients with
      acute nausea and not requiring immediate intravenous access, aromatherapy with or
      without oral ondansetron provides greater nausea relief than oral ondansetron
      alone.

PMID- 29463462
TI  - Vasoactive Inotropic Score as a Predictor of Mortality in Adult Patients With
      Cardiogenic Shock: Medical Therapy Versus ECMO.
AB  - INTRODUCTION AND OBJECTIVES: This study investigated whether the vasoactive
      inotropic score (VIS) is independently predictive of mortality in cardiogenic
      shock (CS). METHODS: This study was retrospective, observational study. Patients
      who were admitted to the cardiac intensive care unit from January 2012 to
      December 2015 were screened, and 493 CS patients were finally enrolled. To
      quantify pharmacologic support, the patients were divided into 5 groups based on
      a quintile of VIS: 1 to 10, 11 to 20, 21 to 38, 39 to 85, and > 85. The primary
      outcome was in-hospital mortality. RESULTS: In-hospital mortalities in the 5 VIS
      groups in increasing order were 8.2%, 14.1%, 21.1%, 32.0%, and 65.7%,
      respectively (P < .001). Multivariable analysis indicated that VIS ranges of 39
      to 85 (aOR, 3.85; 95%CI, 1.60-9.22; P = .003) and over 85 (aOR, 10.83; 95%CI,
      4.43-26.43; P < .001) remained significant prognostic predictors for in-hospital
      mortality. With multiple logistic regression to remove any confounding effects,
      we found that the localized regression lines regarding the odds of death
      intersected each other's (medical therapy alone and combined extracorporeal
      membrane oxygenation group) path at VIS = 130. In contrast to linear correlation
      between VIS and mortality for patients treated with medical therapy alone, there
      was little association between a VIS of 130 or more and the probability of in
      hospital mortality for patients who were treated with extracorporeal membrane
      oxygenation. CONCLUSIONS: A high level of vasoactive inotropic support during the
      first 48hours was significantly associated with increased in-hospital mortality
      in adult CS patients.

PMID- 29463463
TI  - Effect of primary admission to burn centers on the outcomes of severely burned
      patients.
AB  - OBJECTIVE: Burns represent a special form of severe trauma. Due to long
      hospitalization, rehabilitation, and extensive scar treatment, severe burn
      injuries rank among the most expensive traumatic injuries regarding associated
      health care costs. The presented single-burn-center experiences evaluated the
      effects of primary versus secondary burn intensive care unit (BICU) admissions on
      outcomes in severely burned patients. METHODS: Within 30 months, 186 patients
      were admitted to the BICU. The cases were divided into two groups depending on
      their admission type: "primary" vs. "secondary". All patients were analyzed
      retrospectively regarding the need for surgery, encountered complications, time
      of hospitalization and overall survival. RESULTS: The incidence of primary BICU
      admissions was 65.1%. Both patient groups were comparable regarding demographics,
      comorbidities, % TBSA burn, associated inhalation injuries, ABSI scores and
      intubation rates (p>0.05). Both groups received similar numbers of operations and
      had overall comparable mortality rates (p>0.05). However, duration until first
      burn excision, length of ventilation, as well as BICU- and overall hospital
      length of stay were significantly shorter in the "primary"- compared to the
      "secondary" group (p<0.05). CONCLUSION: Several burn societies have published
      precise criteria of when a patient needs to be referred to a burn center. In the
      presented series, patients that were primarily treated at a BICU showed
      significantly better outcomes regarding several parameters. In order to further
      optimize treatment of burn patients it therefore appears that precise initial
      assessment and if appropriate respective primary transport to dedicated burn
      centers needs to be re-emphasized, especially among first- and emergency care
      providers.

PMID- 29463464
TI  - Epididymal sperm from Spix's yellow-toothed cavies sperm successfully
      cryopreserved in Tris extender with 6% glycerol and 20% egg yolk.
AB  - As a non-threatened hystricognath rodent species, Spix's yellow-toothed cavies
      can be used as a model for the development of assisted reproductive techniques
      for the conservation of closely related species. The objective was to establish a
      functional protocol for cryopreservation of epididymal sperm from these cavies.
      Twelve sexually mature males, ~2 y old and weighing ~300 g, were euthanized.
      Sperm were recovered by retrograde flushing of the vas deferens and cauda
      epididymis with Tris extender. Thereafter, sperm were extended in Tris plus 20%
      egg yolk, with 3%, 6% or 9% glycerol or dimethyl sulfoxide (DMSO), placed in 0.25
      mL straws and cryopreserved in liquid nitrogen. Sperm concentration, motility
      (using computer-assisted sperm analysis; CASA), plasma membrane integrity,
      osmotic response, morphology and sperm binding-ability were determined in fresh
      and frozen-thawed sperm. For most sperm endpoints, glycerol was a more desirable
      cryoprotectant than DMSO. Data (mean +/- SEM) were similar with use of 3%, 6%,
      and 9% glycerol (P > 0.05) in osmotic response (40.66 +/- 6.3%, 42.5 +/- 7.1%,
      and 39.5 +/- 5.0% respectably), and membrane integrity (55.17 +/- 5.5%, 68.4 +/-
      4.1%, and 59.1 +/- 4.9% respectably). Among concentrations assessed, the use of
      6% glycerol resulted in the greatest (P < 0.05) post-thaw values for total
      motility (60.9 +/- 4.4%), rapid subpopulation motility (27.7 +/- 3.1%) and sperm
      binding capability (227.0 +/- 20.2). In conclusion, epididymal sperm from the
      Spix's yellow-toothed cavies (G. spixii) are optimally cryopreserved in Tris
      extender with 6% glycerol and 20% egg yolk.

PMID- 29463465
TI  - Secondary pulmonary syphilis: Case report and review of literature.
AB  - INTRODUCTION: Syphilis is a sexually transmitted disease that can affect numerous
      organs in its secondary or tertiary stages. We describe a case of secondary
      syphilis with pulmonary involvement and we present a literature review. PATIENTS
      AND METHODS: A 69-year-old male patient was admitted to hospital for dyspnoea and
      extended papular exanthema with palmoplantar involvement. The serological test
      for syphilis was positive. Ocular examination showed bilateral papillitis and
      retinal haemorrhage. Chest radiography revealed an interstitial alveolar
      infiltrate predominantly in the upper lobes, mild pleural effusion and hilar
      adenopathy. These infiltrates were slightly hypermetabolic on PET scan suggesting
      inflammatory or infectious origin. Treatment with intravenous penicillin G was
      effective on cutaneous, ocular and pulmonary manifestations. DISCUSSION: Lung
      involvement in secondary syphilis is poorly known and rarely described. We found
      27 cases of pulmonary syphilis reported in English and the main European
      languages since 1967. Mean age at diagnosis was 46 years with clear male
      predominance (89%). HIV co-infection was declared in 5 cases. Treponema pallidum
      was found in 6 patients using PCR on bronchoalveolar lavage (BAL) (3 patients) or
      on a lung biopsy (1 patient), immunohistochemistry (IHC) on BAL (1 patient) and
      Giemsa staining on a pleural fluid sample (1 patient). Chest X-rays may show
      unilateral or bilateral infiltrates or nodules with or without pleural effusion
      or hilar adenopathy. Sub-pleural involvement is frequent and penicillin is the
      treatment of choice. CONCLUSION: Pulmonary syphilitic involvement should be
      suspected where pulmonary symptoms or radiological changes occur in secondary
      syphilis. IHC, special staining or PCR on BAL, pleural fluid or lung tissue are
      useful for the identification of spirochetes.

PMID- 29463466
TI  - Right ventricular dysfunction in congenitally corrected transposition of the
      great arteries and risk of ventricular tachyarrhythmia and sudden death.
AB  - BACKGROUND: It is unknown whether systemic right ventricular (SRV) dysfunction
      confers increased risk for sudden death in congenitally corrected transposition
      of the great arteries (ccTGA). We sought to define risk of ventricular
      arrhythmias and sudden death attributable to systemic right ventricular
      dysfunction in ccTGA. METHODS: The study cohort is comprised of adult patients
      with a diagnosis of ccTGA. Clinical information and clinical outcomes including
      ICD therapy, incidence of VT/VF, and cause of death were reviewed. RESULTS: 129
      patients with ccTGA were followed for 7.2 +/- 3.4 years. Mean SRV ejection
      fraction (SRVEF) was 39% (n = 56 with an EF <35%). Significant documented
      arrhythmia (sustained VT requiring defibrillation or cardiac arrest due to VT/VF)
      occurred in 13/56 patients (23%) with SRV EF <35% compared with 2/73 (3%) with
      SRV EF >35% (p < 0.001). There was no significant difference in age at death,
      death from documented arrhythmia, or death from all cause between patients with
      SRV EF <35% and >35%. However, risk of sudden death was higher in patients with
      SRV EF <35% (16% vs 1%, p = 0.002). The combined clinical endpoint of ICD
      therapy, clinically significant VT/VF, and sudden death was significantly higher
      in patients with SRV EF <35% than in patients with SRV EF >35%, independent of
      the presence of LV EF <35% (p < 0.001). CONCLUSIONS: Dysfunction of the systemic
      RV in ccTGA increases the risk of sudden death and clinically significant
      ventricular tachyarrhythmias. Further study is needed to determine if ventricular
      tachyarrhythmias comprise the primary cause of sudden death in these patients and
      if ICDs offer any significant mortality benefit.

PMID- 29463467
TI  - PS. It was me all along! Emergence of phosphatidylserine in the procoagulant
      state in atrial fibrillation.

PMID- 29463468
TI  - Leaving some myths about neurocysticercosis and epilepsy.

PMID- 29463469
TI  - Lay epilepsy organizations: The key for research funding?

PMID- 29463470
TI  - Metabolic Kinases Moonlighting as Protein Kinases.
AB  - Protein kinases regulate every aspect of cellular activity, whereas metabolic
      enzymes are responsible for energy production and catabolic and anabolic
      processes. Emerging evidence demonstrates that some metabolic enzymes, such as
      pyruvate kinase M2 (PKM2), phosphoglycerate kinase 1 (PGK1), ketohexokinase (KHK)
      isoform A (KHK-A), hexokinase (HK), and nucleoside diphosphate kinase 1 and 2
      (NME1/2), that phosphorylate soluble metabolites can also function as protein
      kinases and phosphorylate a variety of protein substrates to regulate the Warburg
      effect, gene expression, cell cycle progression and proliferation, apoptosis,
      autophagy, exosome secretion, T cell activation, iron transport, ion channel
      opening, and many other fundamental cellular functions. The elevated protein
      kinase functions of these moonlighting metabolic enzymes in tumor development
      make them promising therapeutic targets for cancer.

PMID- 29463473
TI  - Poorly Controlled Homocystinuria: A Rare Cause of Ischemic Priapism?
AB  - We report on the 1st case of ischemic priapism secondary to poorly controlled
      homocystinuria. Homocystinuria is a rare, autosomal recessive, inherited disorder
      of metabolism that is caused by a deficiency of cystathionine synthase, leading
      to marked hyperhomocysteinemia. Arterial and/or venous thromboemboli are a major
      cause of mortality and morbidity in patients with homocystinuria. Untreated
      patients have a 50% chance of having a vascular event by 30 years of age.
      Increased homocysteine levels have been reported to upregulate prothrombotic
      factors and downregulate antithrombotic factors; in particular, increased
      homocystinuria has been found to downregulate nitric oxide (NO). Mice that are
      deficient in NO synthase in the cavernosal smooth muscles have a higher incidence
      of priapism. Decrease in NO synthase causes downregulation of cyclic guanosine
      monophosphate, phosphodiesterase type 5A, and Rho A/Rho-kinase. Because
      persistently increased homocysteine also downregulates NO, a similar mechanism
      could be proposed for priapism secondary to homocystinuria. In patients
      presenting with priapism, specific features of homocystinuria should be sought;
      in selected patients, screening with plasma total homocysteine might be
      appropriate. Ischemic priapism secondary to homocystinuria appears to respond
      well to the standard treatment options of aspiration, intracavernosal injection
      with phenylephrine, and, if required, a shunting procedure. Johnson M, Murphy E,
      Raheem A, Ralph D. Poorly Controlled Homocystinuria: A Rare Cause of Ischemic
      Priapism? Sex Med 2018;6:171-173.

PMID- 29463471
TI  - IL-4 Receptor Alpha Signaling through Macrophages Differentially Regulates Liver
      Fibrosis Progression and Reversal.
AB  - : Chronic hepatitis leads to liver fibrosis and cirrhosis. Cirrhosis is a major
      cause of worldwide morbidity and mortality. Macrophages play a key role in
      fibrosis progression and reversal. However, the signals that determine fibrogenic
      vs fibrolytic macrophage function remain ill defined. We studied the role of
      interleukin-4 receptor alpha (IL-4Ralpha), a potential central switch of
      macrophage polarization, in liver fibrosis progression and reversal. We
      demonstrate that inflammatory monocyte infiltration and liver fibrogenesis were
      suppressed in general IL-4Ralpha-/- as well as in macrophage-specific IL-4Ralpha
      /- (IL-4RalphaDeltaLysM) mice. However, with deletion of IL-4RalphaDeltaLysM
      spontaneous fibrosis reversal was retarded. Results were replicated by
      pharmacological intervention using IL-4Ralpha-specific antisense
      oligonucleotides. Retarded resolution was linked to the loss of M2-type resident
      macrophages, which secreted MMP-12 through IL-4 and IL-13-mediated phospho-STAT6
      activation. We conclude that IL-4Ralpha signaling regulates macrophage functional
      polarization in a context-dependent manner. Pharmacological targeting of
      macrophage polarization therefore requires disease stage-specific treatment
      strategies. RESEARCH IN CONTEXT: Alternative (M2-type) macrophage activation
      through IL-4Ralpha promotes liver inflammation and fibrosis progression but
      speeds up fibrosis reversal. This demonstrates context dependent, opposing roles
      of M2-type macrophages. During reversal IL-4Ralpha induces fibrolytic MMPs,
      especially MMP-12, through STAT6. Liver-specific antisense oligonucleotides
      efficiently block IL-4Ralpha expression and attenuate fibrosis progression.

PMID- 29463472
TI  - Interferon Gamma Induces Reversible Metabolic Reprogramming of M1 Macrophages to
      Sustain Cell Viability and Pro-Inflammatory Activity.
AB  - Classical activation of M1 macrophages with lipopolysaccharide (LPS) is
      associated with a metabolic switch from oxidative phosphorylation to glycolysis.
      However, the generalizability of such metabolic remodeling to other modes of M1
      macrophage stimulation, e.g. type II interferons (IFNs) such as IFNgamma, has
      remained unknown as has the functional significance of aerobic glycolysis during
      macrophage activation. Here we demonstrate that IFNgamma induces a rapid
      activation of aerobic glycolysis followed by a reduction in oxidative
      phosphorylation in M1 macrophages. Elevated glycolytic flux sustains cell
      viability and inflammatory activity, while limiting reliance on mitochondrial
      oxidative metabolism. Adenosine triphosphate (ATP) distributed by aerobic
      glycolysis is critical for sustaining IFN-gamma triggered JAK (Janus tyrosine
      kinase)-STAT-1 (Signal Transducer and Activator of Transcription 1) signaling
      with phosphorylation of the transcription factor STAT-1 as its signature trait.
      Inhibition of aerobic glycolysis not only blocks the M1 phenotype and pro
      inflammatory cytokine/chemokine production in murine macrophages and also human
      monocytes/macrophages. These findings extend on the potential functional role of
      immuno-metabolism from LPS- to IFNgamma-linked diseases such as atherosclerosis
      and autoimmune disease.

PMID- 29463474
TI  - Sexual Self-Schema Scale for Women-Validation and Psychometric Properties of the
      Polish Version.
AB  - INTRODUCTION: The sexual self-schema is a part of a broader concept of the self
      that is believed to be crucial for intrapersonal and interpersonal sexual
      relationships. AIM: To develop and perform psychometric validation of the Polish
      version of the Sexual Self-Schema Scale for Women (SSSS-W-PL). METHODS: 561 women
      18 to 55 years old were included in the final analysis. Linguistic validation was
      performed in 4 steps in line with the MAPI Institute guidelines. Convergent
      validity was calculated using the Pearson r product-moment coefficient between
      different measures of sexuality (attitudes and experience, behavior, arousal,
      romantic relationship) and SSSS-W-PL total and factor scores. To test
      discriminant validity, we applied hierarchical regression analyses predicting the
      number of lifetime sexual partners, self-rating as a sexual person (1 item, "I
      feel sexually attractive"; on a 5-point Likert scale), and arousability, with
      independent variables being extraversion (Ten-Item Personality Inventory), self
      esteem (Rosenberg Self-Esteem Scale), and the SSSS-W-PL (total and factor
      scores). MAIN OUTCOMES MEASURES: Sexual self-schema was measured by the SSSS-W
      PL, whereas arousability was measured by the arousal/excitement scale of the
      Changes in Sexual Functioning Questionnaire. RESULTS: The mean age of the study
      population was 29.0 +/- 7.6 years. The final scale consisted of 24 adjectives
      grouped within 4 factors: romantic, passionate, direct, and embarrassed. The 4
      factor model accounted for 39% of the variance. The Cronbach alpha was 0.74 for
      the SSSS-W-PL total score and 0.61 to 0.84 for individual factors. Test-retest
      reliability of the scale after 2- to 8-week intervals was 0.87 (95% CI = 0.82
      0.86, P < .001). The increment variances were statistically significant and
      ranged from 3.8% to 11.6%. CONCLUSION: The analysis showed good psychometric
      properties and internal validity of the SSSS-W-PL. The SSSS-W-PL might be helpful
      in consulting and/or providing sexual therapy to gynecologic cancer survivors or
      women with a history of childhood sexual abuse. Nowosielski K, Jankowski KS,
      Kowalczyk R, et al. Sexual Self-Schema Scale for Women-Validation and
      Psychometric Properties of the Polish Version. Sex Med 2018;6:131-142.

PMID- 29463475
TI  - Preliminary Validation of a German Version of the Sexual Complaints Screener for
      Women in a Female Population Sample.
AB  - BACKGROUND: To date, neither the original English nor any of the translated
      versions of the Sexual Complaints Screener for Women (SCS-W) have been tested for
      their psychometric properties. AIM: To evaluate the validity and utility of the
      German version of the SCS-W by assessing content, convergent, and discriminant
      validity. METHODS: A population sample of 309 women (mean age = 26.9 years)
      completed the online survey and had matching data available on the SCS-W and the
      Female Sexual Function Index (FSFI). Spearman bivariate correlations between the
      SCS-W and FSFI domain scores and exploratory factor analysis with principal
      component analysis were conducted. OUTCOMES: Convergent validity was excellent
      for the domain of orgasm, good for satisfaction, dyspareunia, and the total
      questionnaire score, and acceptable for desire, lubrication, arousal, and
      vaginismus. Discriminant validity was present for all domains apart from arousal,
      lubrication, and vaginismus. Varimax rotation suggested an 8-factor model was the
      most robust. CLINICAL IMPLICATIONS: This brief screener seems suitable to provide
      a brief overview of female patients' sexual problems in a clinical setting.
      STRENGTHS AND LIMITATIONS: This is the 1st study to assess the psychometric
      properties of the German version of the SCS-W. However, available information on
      the psychometric properties of the German SCS-W was limited because the validity
      of the screener could not be counterchecked against a clinical diagnosis of
      female sexual dysfunction. CONCLUSION: Our results provide preliminary evidence
      of good validity of the German version of the SCS-W. Overall, the SCS-W can offer
      support for clinicians who are less familiar with sexual medicine and who might
      not routinely discuss sexual issues with their patients. Burri A, Porst H.
      Preliminary Validation of a German Version of the Sexual Complaints Screener for
      Women in a Female Population Sample. Sex Med 2018;6:123-130.

PMID- 29463476
TI  - Defibulation: A Visual Reference and Learning Tool.
AB  - Female genital mutilation type III (infibulation) is achieved by narrowing the
      vaginal orifice by creating a covering seal, accomplished by cutting and
      appositioning the labia minora and/or labia majora, with or without clitoral
      excision. Infibulation is responsible for significant urogynecological,
      obstetrical, and psychosexual consequences that can be treated with defibulation
      (or de-infibulation), an operation that opens the infibulation scar, exposing the
      vulvar vestibule, vaginal orifice, external urethral meatus, and eventually the
      clitoris. This article provides a practical comprehensive, up-to-date visual
      learning tool on defibulation, with information on pre-operative, post-operative,
      and follow-up information. Abdulcadir J, Marras S, Catania L, et al.
      Defibulation: a visual reference and learning tool. J Sex Med 2018;15:601-611.

PMID- 29463477
TI  - The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence,
      Treatment, and Regrets.
AB  - BACKGROUND: Over the past decade, the number of people referred to gender
      identity clinics has rapidly increased. This raises several questions, especially
      concerning the frequency of performing gender-affirming treatments with
      irreversible effects and regret from such interventions. AIM: To study the
      current prevalence of gender dysphoria, how frequently gender-affirming
      treatments are performed, and the number of people experiencing regret of this
      treatment. METHODS: The medical files of all people who attended our gender
      identity clinic from 1972 to 2015 were reviewed retrospectively. OUTCOMES: The
      number of (and change in) people who applied for transgender health care, the
      percentage of people starting with gender-affirming hormonal treatment (HT), the
      estimated prevalence of transgender people receiving gender-affirming treatment,
      the percentage of people who underwent gonadectomy, and the percentage of people
      who regretted gonadectomy, specified separately for each year. RESULTS: 6,793
      people (4,432 birth-assigned male, 2,361 birth-assigned female) visited our
      gender identity clinic from 1972 through 2015. The number of people assessed per
      year increased 20-fold from 34 in 1980 to 686 in 2015. The estimated prevalence
      in the Netherlands in 2015 was 1:3,800 for men (transwomen) and 1:5,200 for women
      (transmen). The percentage of people who started HT within 5 years after the 1st
      visit decreased over time, with almost 90% in 1980 to 65% in 2010. The percentage
      of people who underwent gonadectomy within 5 years after starting HT remained
      stable over time (74.7% of transwomen and 83.8% of transmen). Only 0.6% of
      transwomen and 0.3% of transmen who underwent gonadectomy were identified as
      experiencing regret. CLINICAL IMPLICATIONS: Because the transgender population is
      growing, a larger availability of transgender health care is needed. Other health
      care providers should familiarize themselves with transgender health care,
      because HT can influence diseases and interact with medication. Because not all
      people apply for the classic treatment approach, special attention should be
      given to those who choose less common forms of treatment. STRENGTHS AND
      LIMITATIONS: This study was performed in the largest Dutch gender identity
      clinic, which treats more than 95% of the transgender population in the
      Netherlands. Because of the retrospective design, some data could be missing.
      CONCLUSION: The number of people with gender identity issues seeking professional
      help increased dramatically in recent decades. The percentage of people who
      regretted gonadectomy remained small and did not show a tendency to increase.
      Wiepjes CM, Nota NM, de Blok CJM, et al. The Amsterdam Cohort of Gender Dysphoria
      Study (1972-2015): Trends in Prevalence, Treatment, and Regrets. J Sex Med
      2018;15:582-590.

PMID- 29463478
TI  - Association Between Gender Confirmation Treatments and Perceived Gender
      Congruence, Body Image Satisfaction, and Mental Health in a Cohort of Transgender
      Individuals.
AB  - BACKGROUND: Transgender individuals sometimes seek gender confirmation treatments
      (GCT), including hormone therapy (HT) and/or surgical change of the chest and
      genitalia ("top" and "bottom" gender confirmation surgeries). These treatments
      may ameliorate distress resulting from the incongruence between one's physical
      appearance and gender identity. AIM: The aim was to examine the degree to which
      individuals' body-gender congruence, body image satisfaction, depression, and
      anxiety differed by GCT groups in cohorts of transmasculine (TM) and
      transfeminine (TF) individuals. METHODS: The Study of Transition, Outcomes, and
      Gender is a cohort study of transgender individuals recruited from 3 health plans
      located in Georgia, Northern California, and Southern California; cohort members
      were recruited to complete a survey between 2015-2017. Participants were asked
      about: history of GCT; body-gender congruence; body image satisfaction;
      depression; and anxiety. Participants were categorized as having received: (1) no
      GCT to date; (2) HT only; (3) top surgery; (4) partial bottom surgery; and (5)
      definitive bottom surgery. OUTCOMES: Outcomes of interest included body-gender
      congruence, body image satisfaction, depression, and anxiety. RESULTS: Of the
      2,136 individuals invited to participate, 697 subjects (33%) completed the
      survey, including 347 TM and 350 TF individuals. The proportion of participants
      with low body-gender congruence scores was significantly higher in the "no
      treatment" group (prevalence ratio [PR] = 3.96, 95% CI 2.72-5.75) compared to the
      definitive bottom surgery group. The PR for depression comparing participants who
      reported no treatment relative to those who had definitive surgery was 1.94 (95%
      CI 1.42-2.66); the corresponding PR for anxiety was 4.33 (95% CI 1.83-10.54).
      CLINICAL TRANSLATION: Withholding or delaying GCT until depression or anxiety
      have been treated may not be the optimal treatment course given the benefits of
      reduced levels of distress after undergoing these interventions. CONCLUSIONS:
      Strengths include the well-defined sampling frame, which allowed correcting for
      non-response, a sample with approximately equal numbers of TF and TM
      participants, and the ability to combine data on HT and gender confirmation
      surgeries. Limitations include the cross-sectional design and the fact that
      participants may not be representative of the transgender population in the
      United States. Body-gender congruence and body image satisfaction were higher,
      and depression and anxiety were lower among individuals who had more extensive
      GCT compared to those who received less treatment or no treatment at all. Owen
      Smith AA, Gerth J, Sineath RC, et al. Association Between Gender Confirmation
      Treatments and Perceived Gender Congruence, Body Image Satisfaction and Mental
      Health in a Cohort Of Transgender Individuals. J Sex Med 2018;15:591-600.

PMID- 29463479
TI  - The Moderating Role of Leader-Member Exchange in the Relationships Between
      Emotional Labor and Burnout in Clinical Nurses.
AB  - PURPOSE: This study aimed to identify the moderating effect of leader-member
      exchange in the relationship between emotional labor and burnout among clinical
      nurses. METHODS: A cross-sectional study design was used. Participants were 170
      registered nurses working in the general wards of two tertiary hospitals in
      Seoul, South Korea. The data were collected through convenience sampling using
      self-report measures of emotional labor, leader-member exchange, and burnout. The
      data were analyzed using hierarchical multiple regression. RESULTS: Data from 165
      nurses (response rate 97.1%) were utilized. The mean age of the participants was
      28.42 years (SD = 5.43), and their mean years of experience as a nurse was 5.80
      years (SD = 5.51). First, emotional modulation efforts in their profession and
      patient-focused emotional suppression (both factors of emotional labor) showed
      significant negative and positive effects, respectively, on burnout. Second,
      leader-member exchange showed a significant negative effect on burnout. Finally,
      when controlling for marital status and work unit, leader-member exchange had a
      moderating effect on the relationship between burnout and the two aforementioned
      factors of emotional labor. CONCLUSION: The results of this study suggest that as
      a way to reduce burnout, institutional support to enhance leader-member exchange
      should be established for nurses who are experiencing emotional labor.

PMID- 29463480
TI  - Prevalence and Influencing Factors of Metabolic Syndrome Among Persons with
      Physical Disabilities.
AB  - PURPOSE: Metabolic syndrome is an important cluster of coronary heart disease
      risk factors. However, it remains unclear to what extent metabolic syndrome is
      associated with demographic and potentially modifiable lifestyle factors among
      Korean persons with physical disabilities. This study aimed to determine the
      prevalence and influencing factors of metabolic syndrome among persons with
      physical disabilities using the Korean National Health Insurance Service-National
      Sample Cohort. METHODS: The Adult Treatment Panel III criteria were used to
      define metabolic syndrome influencing factors and prevalence, which were
      evaluated in a representative sample from the 2013 Korean National Health
      Insurance Service-National Sample Cohort database. Characteristics were compared
      based on frequency using the chi2 test. The associations between metabolic
      syndrome and its risk factors were estimated using logistic multivariable
      regression analysis. RESULTS: Metabolic syndrome was detected in 31.5% of the
      surveyed persons with physical disabilities. Female sex, age of >=65 years,
      smoking, greater alcohol consumption, physical inactivity, higher body mass
      index, and a family history of diabetes were associated with increased risks of
      metabolic syndrome. CONCLUSION: The major risk factors for metabolic syndrome
      among persons with physical disabilities were obesity and older age. Performing
      physical activity was associated with a lower risk of metabolic syndrome.
      Therefore, we recommend using a continuous obesity management program and
      physical activity to prevent metabolic syndrome among persons with physical
      disabilities.

PMID- 29463481
TI  - Influencing Factors and Consequences of Workplace Bullying among Nurses: A
      Structural Equation Modeling.
AB  - PURPOSE: The purpose of this study was to build and test a model outlining the
      factors related to workplace bullying among nurses. The hypothesized model
      included authentic leadership and a relationship-oriented organizational culture
      as influencing factors, symptom experience and turnover intention as
      consequences, and positive psychological capital as a mediator of workplace
      bullying among nurses. METHODS: We obtained structured questionnaire data from
      301 nurses working at hospitals in South Korea. Based on these data, the
      developed model was verified via a structural equation modeling analysis using
      SPSS and AMOS program. RESULTS: The fit indices of the hypothesized model
      satisfied recommended levels; chi2 = 397.58 (p < .001), normed chi2 (chi2/df) =
      1.82, RMR = .05, TLI = .93, CFI = .94, RMSEA = .05. A relationship-oriented
      organizational culture had a direct effect on workplace bullying (beta = -.48, p
      < .001). Furthermore, workplace bullying had a direct effect on symptom
      experience (beta = .36, p < .001), and this relationship was mediated by positive
      psychological capital (beta = .15, p = .003). Workplace bullying also had an
      indirect effect on turnover intention (beta = .20, p = .007). Finally, symptom
      experience had a direct effect on turnover intention (beta = .31, p = .002).
      CONCLUSION: These results suggest that workplace bullying among nurses may be
      prevented by constructing a relationship-oriented organizational culture, as long
      as employees have sufficient positive psychological capital. In this regard,
      workplace bullying among nurses should be addressed using a comprehensive
      strategy that considers both individual and organizational factors.

PMID- 29463482
TI  - Contributions and Limitations of National Cervical Cancer Screening Program in
      Korea: A Retrospective Observational Study.
AB  - PURPOSE: The purpose of this study was to evaluate the contributions and
      limitations of the cervical cancer screening test with accuracy in Korea.
      METHODS: This was a retrospective observational study. The study population
      consisted of all participants who underwent cervical cancer screening test from
      2009 to 2014. The data were obtained from National Health Information Database
      (NHID) which represents medical use records of most Koreans. As the indices for
      contributions and limitations of the screening test, crude detection rate,
      incidence rate of interval cancer, sensitivity, specificity, and positive
      predictive value were used. RESULTS: The crude detection rate of screening test
      per 100,000 participants increased from 100.7 in 2009 to 102.1 in 2014. The
      incidence rate of interval cancer per 100,000 negatives decreased from 13.0 in
      2009 to 10.2 in 2014. The sensitivities of screening test were 88.7% in 2009 and
      91.2% in 2014, and the specificities were 98.5% in 2009 and 97.7% in 2014. The
      positive predictive value of screening decreased from 6.2% in 2009 to 4.3% in
      2014. CONCLUSION: The Korean national cervical cancer screening program has
      improved in accuracy and has contributed to detection of early stage of cervical
      cancer over the years. Along with efforts to promote participation in cancer
      screening programs, quality control over the screening program should be
      enhanced.

PMID- 29463483
TI  - The Experience of Paid Family-Care Workers of People with Dementia in South
      Korea.
AB  - PURPOSE: The South Korean government introduced the universal long-term care
      insurance program in 2008 that created a new employment category of "paid family
      care worker" to assist the elderly with chronic illnesses including dementia. The
      aim of this study was to understand the lived experience of paid family-care
      workers of people with dementia in South Korea. METHODS: The study was a
      qualitative research design underpinned by interpretive description principles
      involving eight paid family-care workers. The participants were recruited by
      attaching the advertisement flyer in a notice board of an educational facility
      for paid family-care workers. RESULTS: Paid family-care workers struggled to
      manage the behavioral and psychological symptoms of their care recipients. Their
      workloads created physical, emotional, social, and financial burdens. However,
      the care-giving activities were encouraged through their sense of responsibility,
      filial piety, and personal religious beliefs. Financial subsidies from the
      government and help received from others were also identified as encouragements.
      The education course provided to them assisted them to improve their dementia
      care capabilities. CONCLUSION: Understanding paid family-care workers' lived
      experience in dementia care in South Korea assists with the identification of
      their educational needs and level of support they require to improve dementia
      care in the home care environment. A number of suggestions are made to increase
      paid family-care workers' knowledge, clinical skills, and job satisfaction to
      reduce their burdens and work-related incidents, such as challenging behaviors
      from those being cared for.

PMID- 29463484
TI  - The Effects of an Interactive Nursing Skills Mobile Application on Nursing
      Students' Knowledge, Self-efficacy, and Skills Performance: A Randomized
      Controlled Trial.
AB  - PURPOSE: Clinical nursing practice is important because it helps nursing students
      experience realities of clinical nursing that cannot be learned through
      theoretical education. This study aimed to evaluate the effect of an interactive
      nursing skills mobile application for nursing students. METHODS: Sixty-six senior
      nursing students were randomly assigned to experimental or control groups. The
      experimental group used an interactive nursing skills mobile application for 1
      week. The control group was provided with a mobile application containing
      noninteractive nursing video contents for 1 week. Before (pre-test) and 1 week
      after (post-test) using the mobile application, participants' knowledge of
      clinical nursing skills, self-efficacy of nursing practice, and nursing skills
      performance were assessed. RESULTS: The experimental group showed a significantly
      higher value for knowledge after 1 week of treatment via their mobile application
      than the control group (t = 3.34, p = .001). In addition, they showed
      significantly improved self-efficacy before and after intervention (t = 2.46, p =
      .017) than the control group. The experimental group's nursing skills performance
      was also significantly enhanced after intervention (t = 7.05, p < .001), with a
      significant difference in the degree of improvement (t = 4.47, p < .001).
      CONCLUSION: The interactive learner-centered nursing education mobile application
      with systematic contents was an effective method for students to experience
      practical nursing skills. Developing and applying a mobile application with other
      nursing contents that can be effectively used across all range of nursing
      students is recommended.

PMID- 29463485
TI  - Effect of Structured Bed Exercise on Uterine Contractions, Fetal Heart Rate
      Patterns, and Maternal Psychophysical Symptoms of Hospitalized High-Risk Pregnant
      Women: A Randomized Control Trial.
AB  - PURPOSE: This study examined the effect on uterine contraction frequency (UCF),
      blood pressure (BP), heart rate (HR), fetal heart rate (FHR) patterns and
      psychophysical symptoms (physical discomfort, anxiety, and depression) of
      structured bed exercise (SBE) in hospitalized high-risk pregnant women prescribed
      bed rest. METHODS: Forty-five hospitalized high risk pregnant women at >24 weeks
      of pregnancy prescribed bed rest were randomly assigned to the experimental or
      control group. From January to May 2014, data were collected using electronic
      fetal monitoring and patient monitoring of UCF, BP, HR and FHR patterns, and
      psychophysical symptoms were measured using the antenatal physical discomfort
      scale, state-trait anxiety scale, and Edinburgh postnatal depression scale.
      RESULTS: UCF, BP, HR, and FHR patterns (rate, variability, acceleration, and
      deceleration) did not differ significantly between the experimental and control
      groups. The experimental group showed a significant increase in baseline FHR
      after SBE within the normal range, and after SBE, it reduced to the FHR before
      SBE. The variability, acceleration and deceleration of FHR before and after SBE
      did not differ significantly between two groups. Moreover, there was no
      statistically significant difference before and after SBE in the experimental
      group. Also, the experimental group showed statistically significant decreases in
      physical discomfort score. However, there were no significant differences in
      depression and anxiety score between two groups. CONCLUSIONS: SBE in hospitalized
      high-risk pregnant women under bed rest did not increase the risk to the fetus,
      and relieved physical discomfort and anxiety. Therefore, SBE should be considered
      as a nursing intervention in hospitalized high-risk pregnant women.

PMID- 29463486
TI  - Burnout Study of Clinical Nurses in Vietnam: Development of Job Burnout Model
      Based on Leiter and Maslach's Theory.
AB  - PURPOSE: This study aimed to create a Vietnamese version of both the Maslach
      Burnout Inventory-General Survey (MBI-GS) and Areas of Worklife Scale (AWS) to
      assess the burnout state of Vietnamese clinical nurses and to develop a causal
      model of burnout of clinical nurses. METHODS: We conducted a descriptive design
      using a cross-sectional survey. The questionnaire was hand divided directly by
      nursing departments to 500 clinical nurses in three hospitals. Vietnamese MBI-GS
      and AWS were then examined for reliability and validity. We used the revised
      exhaustion +1 burnout classification to access burnout state. We performed path
      analysis to develop a Vietnamese causal model based on the original model by
      Leiter and Maslach's theory. RESULTS: We found that both scales were reliable and
      valid for assessing burnout. Among nurse participants, the percentage of severe
      burnout was 0.7% and burnout was 15.8%, and 17.2% of nurses were exhausted. The
      best predictor of burnout was "on-duty work schedule" that clinical nurses have
      to work for 24 hours. In the causal model, we also found similarity and
      difference pathways in comparison with the original model. CONCLUSION: Vietnamese
      MBI-GS and AWS were applicable to research on occupational stress. Nearly one
      fifth of Vietnamese clinical nurses were working in burnout state. The causal
      model suggested a range of factors resulting in burnout, and it is necessary to
      consider the specific solution to prevent burnout problem.

PMID- 29463488
TI  - Digital Health Interventions for Adults With Type 2 Diabetes: Qualitative Study
      of Patient Perspectives on Diabetes Self-Management Education and Support.
AB  - BACKGROUND: The prevalence of type 2 diabetes is increasing globally, and health
      services in many countries are struggling with the morbidity, mortality, and
      costs associated with the complications of this long-term condition. Diabetes
      self-management education (DSME) and behavioral support can reduce the risks of
      developing diabetes-related complications and improve glycemic control. However,
      their uptake is low. Digital health interventions (DHI) can provide sustained
      support and may overcome challenges associated with attending diabetes self
      management sessions. They have the potential for delivery at multiple locations
      at convenient times, anonymity, and presentation of content in attractive and
      tailored formats. This study investigates the needs and wants of patients with
      type 2 diabetes to inform the development of digital self-management education
      and support. OBJECTIVE: The objective of this study was to explore patient
      perspectives on unmet needs for self-management and support and the role of DHI
      in adults living with type 2 diabetes. METHODS: This study used a qualitative
      approach based on data generated from 4 focus groups with 20 patients. RESULTS:
      The data generated by the focus groups illustrated the significant burden that
      the diagnosis of diabetes places on many patients and the negative impacts on
      their emotional well-being, work, social life, and physical health. Although
      patients' experiences of the health care services varied, there was agreement
      that even the best services were unable to meet all users' needs to support the
      emotional regulation, psychological adjustment, and behavioral changes needed for
      successful self-management. CONCLUSIONS: By focusing on medical management and
      information provision, existing health care services and education programs may
      not be adequately meeting all the needs of patients with type 2 diabetes. DHIs
      have the potential to improve access to DSME and behavioral support and extend
      the range of content offered by health services to fit with a wider range of
      patient needs. Features that could help DHIs address some of the unmet needs
      described by participants in this study included placing an emphasis on emotional
      and role management, being available at all times, having up-to-date evidence
      based guidance for patients, and providing access to peer-generated and
      professional advice.

PMID- 29463487
TI  - Users, Uses, and Effects of Social Media in Dietetic Practice: Scoping Review of
      the Quantitative and Qualitative Evidence.
AB  - BACKGROUND: Social media platforms are increasingly used by registered dietitians
      (RDs) to improve knowledge translation and exchange in nutrition. However, a
      thorough understanding of social media in dietetic practice is lacking.
      OBJECTIVE: The objective of this study was to map and summarize the evidence
      about the users, uses, and effects of social media in dietetic practice to
      identify gaps in the literature and inform future research by using a scoping
      review methodology. METHODS: Stages for conducting the scoping review included
      the following: (1) identifying the research question; (2) identifying relevant
      studies through a comprehensive multidatabase and gray literature search
      strategy; (3) selecting eligible studies; (4) charting the data; and (5)
      collating, summarizing, and reporting results for dissemination. Finally,
      knowledge users (RDs working for dietetic professional associations and public
      health organizations) were involved in each review stage to generate practical
      findings. RESULTS: Of the 47 included studies, 34 were intervention studies, 4
      were descriptive studies, 2 were content analysis studies, and 7 were expert
      opinion papers in dietetic practice. Discussion forums were the most frequent
      social media platform evaluated (n=19), followed by blogs (n=13) and social
      networking sites (n=10). Most studies targeted overweight and obese or healthy
      users, with adult populations being most studied. Social media platforms were
      used to deliver content as part of larger multiple component interventions for
      weight management. Among intervention studies using a control group with no
      exposition to social media, we identified positive, neutral, and mixed effects of
      social media for outcomes related to users' health behaviors and status (eg,
      dietary intakes and body weight), participation rates, and professional
      knowledge. Factors associated with the characteristics of the specific social
      media, such as ease of use, a design for quick access to desired information, and
      concurrent reminders of use, were perceived as the main facilitators to the use
      of social media in dietetic practice, followed to a lesser extent by interactions
      with an RD and social support from fellow users. Barriers to social media use
      were mostly related to complicated access to the site and time issues.
      CONCLUSIONS: Research on social media in dietetic practice is at its infancy, but
      it is growing fast. So far, this field of research has targeted few social media
      platforms, most of which were assessed in multiple-component interventions for
      weight management among overweight or obese adults. Trials isolating the effects
      and mechanisms of action of specific social media platforms are needed to draw
      conclusions regarding the effectiveness of those tools to support dietetic
      practice. Future studies should address barriers and facilitators related to the
      use of social media written by RDs and should explore how to make these tools
      useful for RDs to reach health consumers to improve health through diet.

PMID- 29463489
TI  - Mobile App Delivery of the EORTC QLQ-C30 Questionnaire to Assess Health-Related
      Quality of Life in Oncological Patients: Usability Study.
AB  - BACKGROUND: Mobile apps are evolving in the medical field. However, ongoing
      discussions have questioned whether such apps are really valuable and whether
      patients will accept their use in day-to-day clinical life. Therefore, we
      initiated a usability study in our department. OBJECTIVE: We present our results
      of the first app prototype and patient testing of health-related quality of life
      (HRQoL) assessment in oncological patients. METHODS: We developed an app
      prototype for the iOS operating system within eight months in three phases:
      conception, initial development, and pilot testing. For the HRQoL assessment, we
      chose to implement only the European Organization for Research and Treatment of
      Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30; German version 3).
      Usability testing was conducted for three months. Participation was voluntary and
      pseudonymized. After completion of the QLQ-C30 questionnaire using iPads provided
      by our department, we performed a short survey with 10 questions. This survey
      inquired about patients' opinions regarding general aspects, including technical
      advances in medicine, mobile and app assistance during cancer treatment, and the
      app-specific functions (eg, interface and navigation). RESULTS: After logging
      into the app, the user can choose between starting a questionnaire, reviewing
      answers (administrators only), and logging out. The questionnaire is displayed
      with the same information, questions, and answers as on the original QLQ-C30
      sheet. No alterations in wording were made. Usability was tested with 81
      patients; median age was 55 years. The median time for completing the HRQoL
      questionnaire on the iPad was 4.0 minutes. Of all participants, 84% (68/81) owned
      a mobile device. Similarly, 84% (68/81) of participants would prefer a mobile
      version of the HRQoL questionnaire instead of a paper-based version. Using the
      app in daily life during and after cancer treatment would be supported by 83%
      (67/81) of participants. In the prototype version of the app, data were stored on
      the device; in the future, 79% (64/81) of the patients would agree to transfer
      data via the Internet. CONCLUSIONS: Our usability test showed good results
      regarding attractiveness, operability, and understandability. Moreover, our
      results demonstrate a high overall acceptance of mobile apps and telemedicine in
      oncology. The HRQoL assessment via the app was accepted thoroughly by patients,
      and individuals are keen to use it in clinical routines, while data privacy and
      security must be ensured.

PMID- 29463490
TI  - Motivational Interviewing and Medication Review in Coronary Heart Disease
      (MIMeRiC): Protocol for a Randomized Controlled Trial Investigating Effects on
      Clinical Outcomes, Adherence, and Quality of Life.
AB  - BACKGROUND: Preventive treatment goals for blood pressure and cholesterol levels
      continue to be unmet for many coronary patients. The effect of drug treatment
      depends on both its appropriateness and the patients' adherence to the treatment
      regimen. There is a need for adherence interventions that have a measurable
      effect on clinical outcomes. OBJECTIVE: This study aims to evaluate the effects
      on treatment goals of an intervention designed to improve patient adherence and
      treatment quality in secondary prevention of coronary heart disease. A protocol
      for the prespecified process evaluation of the trial is published separately.
      METHODS: The Motivational Interviewing and Medication Review in Coronary heart
      disease (MIMeRiC) trial is a prospective, randomized, outcomes-blinded trial
      designed to compare individualized follow-up by a clinical pharmacist using
      motivational interviewing (MI) and medication review with standard follow-up.
      Patients were randomized to 2 groups after stratification according to their
      beliefs about medicines. After standard follow-up at the cardiology clinic,
      patients in the intervention group are seen individually by a clinical pharmacist
      2 to 5 times as required over 7 months, at the clinic. The pharmacist reviews
      each patient's medication and uses MI to manage any problems with prescribing and
      adherence. The primary study outcome is the proportion of patients who have
      reached the treatment goal for low-density lipoprotein cholesterol by 12 months
      after discharge. Secondary outcomes are the effects on patient adherence,
      systolic blood pressure, disease-specific quality of life, and health care use.
      RESULTS: The protocol for this study was approved by the Regional Ethics
      Committee, Linkoping, in 2013. Enrollment started in October 2013 and ended in
      December 2016 when 417 patients had been included. Follow-up data collection will
      conclude in March 2018. Publication of the primary and secondary outcome results
      from the MIMeRiC trial is anticipated in 2019. CONCLUSIONS: The MIMeRiC trial
      will assess the effectiveness of an intervention involving medication reviews and
      individualized support. The results will inform the continued development of
      support for this large group of patients who use preventive medicines for
      lifelong treatment. The design of this adherence intervention is based on a
      theoretical framework and is the first trial of an intervention that uses beliefs
      about medicines to individualize the intervention protocol. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02102503; https://clinicaltrials.gov/ct2/show/NCT02102503
      (Archived by WebCite at http://www.webcitation.org/6x7iUDohy).

PMID- 29463492
TI  - Ecuadorian Cancer Patients' Preference for Information and Communication
      Technologies: Cross-Sectional Study.
AB  - BACKGROUND: The instantaneous spread of information, low costs, and broad
      availability of information and communication technologies (ICTs) make them an
      attractive platform for managing care, patient communication, and medical
      interventions in cancer treatment. There is little information available in Latin
      America about the level of usage of ICTs for and by cancer patients. Our study
      attempts to fill this gap. OBJECTIVE: The aim of this study was to assess the
      level of ICT use and patterns of preferences among cancer patients. METHODS: We
      conducted an anonymous cross-sectional survey study in 500 Ecuadorian cancer
      patients. This questionnaire consisted of 22 items about demographic and clinical
      data, together with the preferences of people who use ICTs. Chi-square, crude,
      and adjusted logistic regressions were performed. RESULTS: Of the total, 43.2%
      (216/500) of participants reported that they had access to the Internet, and
      25.4% (127/500) reported that they neither owned a cell phone nor did they have
      access to the Internet. The Internet constituted the highest usage rate as a
      source of information about malignant diseases (74.3%, 162/218) regardless of age
      (P<.001). With regard to the preferences on how patients would like to use ICTs
      to receive information about diseases, WhatsApp (66.5%, 145/218) and short
      message service (SMS) text messaging (61.0%, 133/218) were widely reported as
      interesting communication channels. Similarly, WhatsApp (72.0%, 157/218) followed
      by SMS (63.8%, 139/218) were reported as the preferred ICTs through which
      patients would like to ask physicians about diseases. Adjusted regression
      analysis showed that patients aged between 40 and 64 years were more likely to be
      interested in receiving information through SMS (odds ratio, OR 5.09, 95% CI 1.92
      13.32), as well as for asking questions to physicians through this same media (OR
      9.78, CI 3.45-27.67) than the oldest group. CONCLUSIONS: WhatsApp, SMS, and email
      are effective and widely used ICTs that can promote communication between cancer
      patients and physicians. According to age range, new ICTs such as Facebook are
      still emerging. Future studies should investigate how to develop and promote ICT
      based resources more effectively to engage the outcomes of cancer patients. The
      widespread use of ICTs narrows the gap between cancer patients with restricted
      socioeconomic conditions and those with wealth and easily available technological
      means, thereby opening up new possibilities in low-income countries.

PMID- 29463491
TI  - A Smartphone App to Promote an Active Lifestyle in Lower-Educated Working Young
      Adults: Development, Usability, Acceptability, and Feasibility Study.
AB  - BACKGROUND: Physical activity (PA) levels are problematic in lower-educated
      working young adults (18-26 years). To promote PA, smartphone apps have great
      potential, but there is no evidence for their effectiveness in this population.
      To increase the likelihood that a newly developed app will be effective,
      formative research and user testing are required. OBJECTIVE: The aim of this
      study was to describe the development, usability, acceptability, and feasibility
      of a new theory- and evidence-based smartphone app to promote an active lifestyle
      in lower-educated working young adults. METHODS: The new app was developed by
      applying 4 steps. First, determinants important to promote an active lifestyle in
      this population were selected. Second, evidence-based behavior change techniques
      were selected to convert the determinants into practical applications. Third, a
      new smartphone app was developed. Fourth, volunteers (n=11, both lower and higher
      educated) tested the app on usability, and lower-educated working young adults
      (n=16) tested its acceptability and feasibility via (think aloud) interviews, a
      questionnaire, and Google Analytics. The app was accordingly adapted for the
      final version. RESULTS: A new Android app, Active Coach, was developed that
      focused on knowledge, attitude, social support, and self-efficacy (based on
      outcomes from step 1), and that applied self-regulation techniques (based on
      outcomes from step 2). The app consists of a 9-week program with personal goals,
      practical tips, and scientific facts to encourage an active lifestyle. To ensure
      all-day and automatic self-monitoring of the activity behavior, the Active Coach
      app works in combination with a wearable activity tracker, the Fitbit Charge.
      Issues detected by the usability test (eg, text errors, wrong messages) were all
      fixed. The acceptability and feasibility test showed that participants found the
      app clear, understandable, and motivating, although some aspects needed to be
      more personal. CONCLUSIONS: By applying a stepwise, user-centered approach that
      regularly consulted the target group, the new app is adapted to their specific
      needs and preferences. The Active Coach app was overall positively evaluated by
      the lower-educated working young adults at the end of the development process.

PMID- 29463493
TI  - Effect of Impulsive Compression Treatment on Postoperative Complications After
      Open Peripheral Vascular Revascularization (In Situ): Protocol for a Randomized
      Control Trial.
AB  - BACKGROUND: In patients with critical leg ischemia (CLI), the standard operative
      choice is an in situ bypass to the lower extremity to improve the patients'
      prognosis and quality of life. Postoperative complications after surgery occur in
      18 % of the patients, prolonging hospitalization and convalescence. The main
      operative complication is edema. This can be prevented by early mobilization or
      stimulation of the natural venous pump in the leg. OBJECTIVE: To investigate
      whether compression therapy with foot pump reduces postoperative edema,
      facilitates wound healing of the operation wounds, promotes healing of ischemic
      ulcers, and shortens hospitalization, increasing and improving the patient's
      subjective quality of life faster. METHODS: The protocol is designed as a
      randomized, unblinded prospective study with 50 patients in each group. Standard
      postoperative routines after bypass surgery, including short-stretch bandaging of
      the operated legs, are compared to supportive stimulation of the venous pump by
      an impulsive compression foot pump. The postoperative edema of the leg is
      measured 10 cm below the patella and 8 cm proximal to the medial malleolus.
      Measurements are performed preoperatively, 1 and 4 days postoperatively and at
      discharge. RESULTS: The primary endpoint is reduction of leg edema by at least
      50%. The secondary endpoint includes earlier mobilization in the pump group and
      decreased length of stay in hospital. Quality of life is evaluated through the
      European Health Related Quality of Life Questionnaire 5 Dimensions (EQ-5D) and
      Vascular Quality of Life Questionnaire-6 (VascuQol-6) questionnaires. The start
      of the study is February 1, 2018, and the end of the study is February 1, 2020.
      First results will be available April 2020. CONCLUSIONS: In orthopedic surgery of
      the lower extremities, the use of foot pumps has shown a reduction of edema and
      thrombosis in risk patients. Although important positive effects may be expected
      after vein bypass surgery, no reports have yet investigated the use of the device
      in vascular-operated patients and no analysis or meta Cochrane reviews are
      available in this field. TRIAL REGISTRATION: ClinicalTrials.gov NCT03192982;
      https://clinicaltrials.gov/ct2/show/NCT03192982 (Archived by WebCite at
      http://www.webcitation.org/6xMZJ06dw).

PMID- 29463494
TI  - How Health Care Professionals Evaluate a Digital Intervention to Improve
      Medication Adherence: Qualitative Exploratory Study.
AB  - BACKGROUND: Medication nonadherence poses a serious and a hard-to-tackle problem
      for many chronic diseases. Electronic health (eHealth) apps that foster patient
      engagement and shared decision making (SDM) may be a novel approach to improve
      medication adherence. OBJECTIVE: The aim of this study was to investigate the
      perspective of health care professionals regarding a newly developed digital app
      aimed to improve medication adherence. Familial hypercholesterolemia (FH) was
      chosen as a case example. METHODS: A Web-based prototype of the eHealth app-MIK
      was codesigned with patients and health care professionals. After user tests with
      patients, we performed semistructured interviews and user tests with 12
      physicians from 6 different hospitals to examine how the functionalities offered
      by MIK could assist physicians in their consultation and how they could be
      integrated into daily clinical practice. Qualitative thematic analysis was used
      to identify themes that covered the physicians' evaluations. RESULTS: On the
      basis of the interview data, 3 themes were identified, which were (1) perceived
      impact on patient-physician collaboration; (2) perceived impact on the patient's
      understanding and self-management regarding medication adherence; and (3)
      perceived impact on clinical decisions and workflow. CONCLUSIONS: The eHealth app
      MIK seems to have the potential to improve the consultation between the patient
      and the physician in terms of collaboration and patient engagement. The impact of
      eHealth apps based on the concept of SDM for improving medication-taking behavior
      and clinical outcomes is yet to be evaluated. Insights will be useful for further
      development of eHealth apps aimed at improving self-management by means of
      patient engagement and SDM.

PMID- 29463496
TI  - Scottish GPs resign from BMA in protest at new contract.

PMID- 29463495
TI  - Healthy Body Image Intervention Delivered to Young Women via Facebook Groups:
      Formative Study of Engagement and Acceptability.
AB  - BACKGROUND: There is increasing interest in using social media sites such as
      Facebook to deliver health interventions so as to expose people to content while
      they are engaging in their usual social media habit. This formative intervention
      development study is novel in describing a preliminary test of using the secret
      group feature of Facebook to deliver a behavioral intervention targeting users of
      indoor tanning beds to reduce their risk of skin cancer. Intervention content was
      designed to challenge body image-related constructs associated with indoor
      tanning through the use of dissonance-inducing content. OBJECTIVE: To evaluate
      engagement with and acceptability of using a secret Facebook group to deliver a
      healthy body image intervention to young women engaged in indoor tanning.
      METHODS: Seventeen young women completed a baseline survey and joined a secret
      Facebook group with intervention content delivered via daily posts for 4 weeks.
      Engagement data was extracted and acceptability was measured via a follow-up
      survey. RESULTS: The study had a high retention rate (94%, [16/17]). On average,
      posts were viewed by 91% of participants, liked by 35%, and commented on by 26%.
      The average comment rate was highest (65%) for posts that elicited comments by
      directly posing questions or discussion topics to the group. Average intervention
      acceptability ratings were highly positive and participants reported feeling
      connected to the group and its topic. Average rates of past 1-month indoor
      tanning reported following the intervention were lower than the baseline rate
      (P=.08, Cohen d=0.47). CONCLUSIONS: This study is novel in demonstrating
      participant engagement with and acceptability of using Facebook secret groups to
      deliver a dissonance-inducing intervention approach that utilizes group-based
      discussions related to body image. The study is also unique within the field of
      skin cancer prevention by demonstrating the potential value of delivering an
      indoor tanning intervention within an interactive social media format. The
      findings suggest that Facebook metrics of intervention post engagement (ie, likes
      and comments) may vary based on post types and that designing specifically
      labeled discussion posts may be helpful for soliciting engagement as well as
      challenging beliefs.

PMID- 29463497
TI  - Psychological interventions used to reduce sports injuries: a systematic review
      of real-world effectiveness.
AB  - OBJECTIVE: To systematically review studies examining the role of psychological
      interventions in injury prevention. The primary research question was: What is
      the real-world effectiveness of psychological intervention in preventing sports
      injuries? DESIGN: Mixed methods systematic review with best evidence synthesis.
      DATA SOURCES: CINAHL, MEDLINE, PsycARTICLES, PsycINFO, SPORTDiscus, Science
      Direct and PubMed. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised
      controlled trials (RCT), non-RCTs that included a comparison group, before and
      after study designs and qualitative methods. Studies were required to outline
      specific unimodal or multimodal psychological interventions used in relation to
      injury prevention in the real-world setting. OUTCOME MEASURE: Studies were
      independently appraised with the Mixed Methods Appraisal Tool. RESULTS: Thirteen
      papers (incorporating 14 studies) met the eligibility criteria, of which 93%
      (13/14) reported a decrease in injury rates (effect size range=0.2-1.21). There
      was an overall moderate risk of bias in reporting (52%). There is a dominance of
      stress management-based interventions in literature due to the prominence of the
      model of stress and athletic injury within the area. SUMMARY/CONCLUSIONS:
      Psychological interventions demonstrate small (0.2) to large (1.21) effects on
      sports injury rates. The research area demonstrates a cumulative moderate risk in
      reporting bias (52%). PROSPERO REGISTRATION NUMBER: CRD42016035879.

PMID- 29463498
TI  - Case for the specialised sports physical therapist to be an essential part of
      professional athlete care: letter from America no. 1.

PMID- 29463499
TI  - Sixty seconds on . . . malnutrition.

PMID- 29463500
TI  - "First, do no harm" is true for NHS management too.

PMID- 29463501
TI  - The next step forward?

PMID- 29463502
TI  - Optical coherence tomography angiography in pseudophakic cystoid macular oedema
      compared to diabetic macular oedema: qualitative and quantitative evaluation of
      retinal vasculature.
AB  - AIMS: To describe optical coherence tomography angiography (OCT-A) abnormalities
      of patients with pseudophakic cystoid macular oedema (PCMO) before and after
      pharmacological resolution, compared with diabetic macular oedema (DMO) and
      normal eyes. METHODS: In this retrospective, observational study, 44 eyes (30
      patients) were included: 15 eyes (15 patients) affected by PCMO; 14 healthy
      fellow eyes used as negative control group; 15 eyes (15 age-matched and sex
      matched patients) with DMO used as positive control group. All patients underwent
      a complete ophthalmological examination at baseline, including OCT-A scans of the
      macula through AngioPlex CIRRUS-5000 (Carl Zeiss Meditec, Dublin, USA). Patients
      with PCMO and DMO were re-evaluated after the pharmacological resolution of
      cystoid macular oedema (CMO). RESULTS: Disruption of parafoveal capillary arcade
      and cystoid spaces in deep capillary plexus (DCP) were frequent in patients with
      PCMO and DMO (73% and 100%, 87% and 100%). Capillary abnormalities and non
      perfusion greyish areas in DCP were more frequent in DMO (P<0.001 and P=0.014).
      Patients with PCMO showed a larger foveal avascular zone area in DCP at baseline
      (P<0.001), which significantly reduced after treatment (P=0.001). Vessel density
      of full-thickness retina and DCP was reduced in patients with PCMO (P=0.022 and
      P=0.001), and no changes were observed after treatment. Interestingly, DCP
      appeared less represented in patients with DMO than PCMO subjects (P=0.001).
      CONCLUSIONS: Patients with PCMO have an impairment of mainly DCP, partially
      reversible after treatment. Furthermore, we disclosed that different alterations
      of the retinal vasculature characterise CMO derived from two different diseases,
      namely PCMO and DMO, and this could be due to their distinct pathophysiology.

PMID- 29463503
TI  - Many CCGs are failing to boost mental health funding, BMA warns.

PMID- 29463504
TI  - Trivalent flu vaccine may provide cross protection of circulating influenza B.

PMID- 29463505
TI  - In This Issue: February.

PMID- 29463506
TI  - Fetal Genotype and Maternal Glucose Have Independent and Additive Effects on
      Birth Weight.
AB  - Maternal glycemia is a key determinant of birth weight, but recent large-scale
      genome-wide association studies demonstrated an important contribution of fetal
      genetics. It is not known whether fetal genotype modifies the impact of maternal
      glycemia or whether it acts through insulin-mediated growth. We tested the
      effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for
      birth weight on birth weight and fetal insulin in 2,051 European mother-child
      pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the
      Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The fetal genetic score
      influenced birth weight independently of maternal FPG and impacted growth at all
      levels of maternal glycemia. For mothers with FPG in the top tertile, the
      frequency of large for gestational age (birth weight >=90th centile) was 31.1%
      for offspring with the highest tertile genetic score and only 14.0% for those
      with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic
      score was not associated with cord insulin or C-peptide. Similar results were
      seen for HAPO participants of non-European ancestry (n = 2,842 pairs). This work
      demonstrates that for any level of maternal FPG, fetal genetics has a major
      impact on fetal growth and acts predominantly through independent mechanisms.

PMID- 29463507
TI  - BMI Can Underestimate Breast Cancer Risk.
AB  - New findings suggest that postmenopausal women with high levels of body fat are
      at increased risk of ER-positive breast cancer, even if their body mass index is
      within the normal range. If confirmed, these results would put many more women at
      elevated risk for breast cancer than was previously thought, with implications
      for the way that healthy-weight women should be counseled to reduce their health
      risks.

PMID- 29463508
TI  - In This Issue: February.

PMID- 29463509
TI  - Ventricular Fibrillation Conversion Testing After Implantation of a Subcutaneous
      Implantable Cardioverter Defibrillator: Report From the National Cardiovascular
      Data Registry.
AB  - BACKGROUND: Compared with transvenous implantable cardioverter defibrillators
      (ICDs), subcutaneous (S)-ICDs require a higher energy for effective
      defibrillation. Although ventricular fibrillation conversion testing (CT) is
      recommended after S-ICD implantation to ensure an adequate margin between the
      defibrillation threshold and maximum device output (80J), prior work found that
      adherence to this recommendation is declining. METHODS: We studied first-time
      recipients of S-ICDs (between September 28, 2012, and April 1, 2016) in the
      National Cardiovascular Database Registry ICD Registry to determine predictors of
      use of CT, predictors of an insufficient safety margin (ISM, defined as
      ventricular fibrillation conversion energy >65J) during testing, and inhospital
      outcomes associated with use of CT. Multivariable logistic regression analysis
      was used to predict use of CT and ISM. Inverse probability weighted logistic
      regression analysis was used to examine the association between use of CT and
      inhospital adverse events including death. RESULTS: CT testing was performed in
      70.7% (n=5624) of 7960 patients with S-ICDs. Although deferral of CT was
      associated with several patient characteristics (including increased body mass
      index, increased body surface area, severely reduced ejection fraction, dialysis
      dependence, warfarin use, anemia, and hypertrophic cardiomyopathy), the facility
      effect was comparatively more important (area under the curve for patient level
      versus generalized linear mixed model: 0.619 versus 0.877). An ISM occurred in
      6.9% (n=336) of 4864 patients without a prior ICD and was more common among white
      patients and those with ventricular pacing on the preimplant ECG, higher
      preimplant blood pressure, larger body surface area, higher body mass index, and
      lower ejection fraction. A risk score was able to identify patients at low (<5%),
      medium (5% to 10%), and high risk (>10%) for ISM. CT testing was not associated
      with a composite of inhospital complications including death. CONCLUSIONS: Use of
      CT testing after S-ICD implantation was driven by facility preference to a
      greater extent than patient factors and was not associated with a composite of
      inhospital complications or death. ISM was relatively uncommon and is associated
      with several widely available patient characteristics. These data may inform ICD
      system selection and a targeted approach to CT.

PMID- 29463510
TI  - Device Thrombosis After Percutaneous Left Atrial Appendage Occlusion Is Related
      to Patient and Procedural Characteristics but Not to Duration of Postimplantation
      Dual Antiplatelet Therapy.
AB  - BACKGROUND: Device-related thrombus (DRT) after left atrial appendage occlusion
      is a worrisome finding with little knowledge about when to expect it and how to
      prevent it. This study sought to investigate correlates of DRT after left atrial
      appendage occlusion, its time of diagnosis, and particularly, association with
      postimplantation dual antiplatelet therapy duration. METHODS AND RESULTS:
      Consecutive patients (n=102) after left atrial appendage occlusion with AMPLATZER
      Cardiac Plug/Amulet (n=59) or WATCHMAN (n=43) were included in a prospective
      registry (October 2011-May 2016). Follow-up was done at 1.5, 3 to 6, and 12
      months postimplantation. DRT was classified as early (at 1.5 month), late (at 3-6
      month), or very late (at 12-month follow-up). Postimplantation dual antiplatelet
      therapy was recommended for 30 to 180 days and decided independently by attending
      physicians. Final analysis included 99 patients, 42 (42.4%) females, with median
      CHA2DS2-VASc of 4.0 (interquartile range [IQR], 3.0-5.0) and median HAS-BLED
      score of 2.0 (IQR, 1.0-3.0). DRTs were observed in 7 (7.1%) patients: 2 (28.6%)
      early, 2 (28.6%) late, and 3 (42.9%) very late. When compared with patients
      without DRT, those with DRT presented more often with a history of prior
      thromboembolism (5 [71.4%] versus 28 [30.4%]; P=0.04), had lower left ventricular
      ejection fraction (50.0 [IQR, 35.0-55.0] versus 60.0 [IQR, 55.0-66.0]; P<0.01),
      and had greater proportion of patients with deep device implantation (6 [85.7%]
      versus 36 [39.1%]; P=0.04) and with larger devices implanted (30.0 mm [IQR, 27.0
      33.0] versus 25.0 mm [IQR, 24.0-28.0]; P<0.01). Postimplantation dual
      antiplatelet therapy duration was not different between the 2 groups (12.4 weeks
      [IQR, 6.0-49.7] with DRT versus 13.0 weeks [IQR, 7.3-26.0] without DRT; P=0.77).
      CONCLUSIONS: In this real-world series, DRT was observed early, late, and very
      late after left atrial appendage occlusion. It was related to patient and
      procedural characteristics but not to postimplantation dual antiplatelet therapy
      duration.

PMID- 29463511
TI  - What Lies Beneath Left Atrial Appendage Occlusion: Know Your Enemy.

PMID- 29463513
TI  - Metabolism of the Pacific oyster, Crassostrea gigas, is influenced by salinity
      and modulates survival to the Ostreid herpesvirus OsHV-1.
AB  - The Pacific oyster, Crassostrea gigas, is an osmoconforming bivalve exposed to
      wide salinity fluctuations. The physiological mechanisms used by oysters to cope
      with salinity stress are energy demanding and may impair other processes, such as
      defense against pathogens. This oyster species has been experiencing recurrent
      mortality events caused by the Ostreid herpesvirus 1 (OsHV-1). The objectives of
      this study were to investigate the effect of salinity (10, 15, 25 and 350/00) on
      energetic reserves, key enzyme activities and membrane fatty acids, and to
      identify the metabolic risk factors related to OsHV-1-induced mortality of
      oysters. Acclimation to low salinity led to increased water content, protein
      level, and energetic reserves (carbohydrates and triglycerides) of oysters. The
      latter was consistent with lower activity of hexokinase, the first enzyme
      involved in glycolysis, up-regulation of AMP-activated protein kinase, a major
      regulator of cellular energy metabolism, and lower activity of catalase, an
      antioxidant enzyme involved in management of reactive oxygen species. Acclimation
      to salinity also involved a major remodeling of membrane fatty acids.
      Particularly, 20:4n-6 decreased linearly with decreasing salinity, likely
      reflecting its mobilization for prostaglandin synthesis in oysters. The survival
      of oysters exposed to OsHV-1 varied from 43% to 96% according to salinity (
      Fuhrmann et al., 2016). Risk analyses showed that activity of superoxide
      dismutase and levels of proteins, carbohydrates, and triglycerides were
      associated with a reduced risk of death. Therefore, animals with a higher
      antioxidant activity and a better physiological condition seemed less susceptible
      to OsHV-1.

PMID- 29463515
TI  - Timing and context of dolphin clicks during and after mine simulator detection
      and marking in the open ocean.
AB  - Two dolphins carrying cameras swam in the ocean as they searched for and marked
      mine simulators - buried, proud or moored. As the animals swam ahead of a boat
      they searched the ocean. Cameras on their harness recorded continuous sound and
      video. Once a target was detected, the dolphins received a marker to take to the
      simulator's location. During search and detection, dolphins made almost
      continuous trains of varying interval clicks. During the marking phase, shorter
      click trains were interrupted by periods of silence. As the dolphins marked
      simulators, they often produced victory squeals - pulse bursts that vary in
      duration, peak frequency and amplitude. Victory squeals were produced on 72% of
      marks. Sometimes after marking, or at other times during their long swims, the
      dolphins produced click packets. Packets typically consisted of two to 10 clicks
      with inter-click intervals of 7-117 ms followed by a silence of 223-983 ms. Click
      packets appeared unrelated with searching or marking. We suggest that the packets
      were used to improve signal to noise ratios for locating a boat or other distant
      object. Victory squeals produced when marking the targets suggest to us that the
      dolphins know when they have succeeded in this multipart task.

PMID- 29463514
TI  - Ecdysone signaling regulates specification of neurons with a male-specific
      neurite in Drosophila.
AB  - Some mAL neurons in the male brain form the ipsilateral neurite (ILN[+]) in a
      manner dependent on FruBM, a male-specific transcription factor. FruBM represses
      robo1 transcription, allowing the ILN to form. We found that the proportion of
      ILN[+]-mALs in all observed single cell clones dropped from ~90% to ~30% by
      changing the heat-shock timing for clone induction from 4-5 days after egg laying
      (AEL) to 6-7 days AEL, suggesting that the ILN[+]-mALs are produced predominantly
      by young neuroblasts. Upon EcR-A knockdown, ILN[+]-mALs were produced at a high
      rate (~60%), even when heat shocked at 6-7 days AEL, yet EcR-B1 knockdown reduced
      the proportion of ILN[+]-mALs to ~30%. Immunoprecipitation assays in S2 cells
      demonstrated that EcR-A and EcR-B1 form a complex with FruBM. robo1 reporter
      transcription was repressed by FruBM and ecdysone counteracted FruBM. We suggest
      that ecdysone signaling modulates the FruBM action to produce an appropriate
      number of male-type neurons.

PMID- 29463516
TI  - Sustained exercise-trained juvenile black carp (Mylopharyngodon piceus) at a
      moderate water velocity exhibit improved aerobic swimming performance and
      increased postprandial metabolic responses.
AB  - The objectives of this study were to examine whether sustained exercise training
      at four water velocities, i.e. nearly still water (control), 1 body length (BL) s
      1, 2 BL s-1 and 4 BL s-1, has effects on swimming performance and digestive
      metabolism in juvenile black carp (Mylopharyngodon piceus). The results
      demonstrated that fish subjected to sustained training at 2 and 4 BL s-1 showed
      significantly higher critical swimming speed (Ucrit) and maximum metabolic rate
      (MMR) over the control group. Fish subjected to sustained training at 1 and 2 BL
      s-1 showed a significantly (30 and 54%) prolonged duration, 14 and 17% higher
      postprandial MO2 increment (i.e. MO2peak), and 62 and 92% more energy expended on
      specific dynamic action (SDA), respectively, after consuming a similar meal over
      fish kept in nearly still water. These results suggest that (1) sustained
      exercise training at a higher speed (2 or 4 BL s-1) had a positive influence on
      the aerobic swimming performance of juvenile M. piceus, which may be associated
      with improved aerobic metabolism; and (2) sustained exercise training at a lower
      speed (1 or 2 BL s-1) resulted in elevated postprandial metabolic responses in
      juvenile M. piceus.

PMID- 29463517
TI  - Common measure of quality of life for people with systemic sclerosis across seven
      European countries: a cross-sectional study.
AB  - OBJECTIVES: The aim of this study was to adapt the Systemic Sclerosis Quality of
      Life Questionnaire (SScQoL) into six European cultures and validate it as a
      common measure of quality of life in systemic sclerosis (SSc). METHODS: This was
      a seven-country (Germany, France, Italy, Poland, Spain, Sweden and UK) cross
      sectional study. A forward-backward translation process was used to adapt the
      English SScQoL into target languages. SScQoL was completed by patients with SSc,
      then data were validated against the Rasch model. To correct local response
      dependency, items were grouped into the following subscales: function, emotion,
      sleep, social and pain and reanalysed for fit to the model, unidimensionality and
      cross-cultural equivalence. RESULTS: The adaptation of the SScQoL was seamless in
      all countries except Germany. Cross-cultural validation included 1080 patients
      with a mean age 58.0 years (SD 13.9) and 87% were women. Local dependency was
      evident in individual country data. Grouping items into testlets corrected the
      local dependency in most country specific data. Fit to the model, reliability and
      unidimensionality was achieved in six-country data after cross-cultural
      adjustment for Italy in the social subscale. The SScQoL was then calibrated into
      an interval level scale. CONCLUSION: The individual SScQoL items have translated
      well into five languages and overall, the scale maintained its construct
      validity, working well as a five-subscale questionnaire. Measures of quality of
      life in SSc can be directly compared across five countries (France, Poland Spain,
      Sweden and UK). Data from Italy are also comparable with the other five countries
      although require an adjustment.

PMID- 29463518
TI  - Relationship between serum urate concentration and clinically evident incident
      gout: an individual participant data analysis.
AB  - OBJECTIVES: To provide estimates of the cumulative incidence of gout according to
      baseline serum urate. METHODS: Using individual participant data from four
      publicly available cohorts (Atherosclerosis Risk in Communities Study, Coronary
      Artery Risk Development in Young Adults Study, and both the Original and
      Offspring cohorts of the Framingham Heart Study), the cumulative incidence of
      clinically evident gout was calculated according to baseline serum urate
      category. Cox proportional hazards modelling was used to evaluate the relation of
      baseline urate categories to risk of incident gout. RESULTS: This analysis
      included 18 889 participants who were gout-free at baseline, with mean (SD) 11.2
      (4.2) years and 212 363 total patient-years of follow-up. The cumulative
      incidence at each time point varied according to baseline serum urate
      concentrations, with 15-year cumulative incidence (95% CI) ranging from 1.1% (0.9
      to 1.4) for <6 mg/dL to 49% (31 to 67) for >=10 mg/dL. Compared with baseline
      serum urate <6 mg/dL, the adjusted HR for baseline serum urate 6.0-6.9 mg/dL was
      2.7, for 7.0-7.9 mg/dL was 6.6, for 8.0-8.9 mg/dL was 15, for 9.0-9.9 mg/dL was
      30, and for >=10 mg/dL was 64. CONCLUSIONS: Serum urate level is a strong non
      linear concentration-dependent predictor of incident gout. Nonetheless, only
      about half of those with serum urate concentrations >=10mg/dL develop clinically
      evident gout over 15 years, implying a role for prolonged hyperuricaemia and
      additional factors in the pathogenesis of gout.

PMID- 29463519
TI  - Effect of pregnancy on disease flares in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: Prior studies found conflicting results about whether lupus is likely
      to flare during or after pregnancy. Using a large cohort of pregnant and non
      pregnant women with lupus, we estimated the effect of pregnancy on disease flares
      in systemic lupus erythematosus. METHODS: Data were collected in the Hopkins
      Lupus Cohort 1987-2015. Women aged 14-45 years with >1 measurement of disease
      activity were included. The time-varying exposures were classified as pregnancy,
      postpartum or non-pregnant/non-postpartum periods. Flares were defined as: (1)
      change in Physician Global Assessment (PGA)>=1 from previous visit and (2) change
      in Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus
      Disease Activity Index (SELENA-SLEDAI)>=4 from previous visit. A stratified Cox
      model estimated HRs with bootstrap 95% CIs. RESULTS: There were 1349 patients,
      including 398 pregnancies in 304 patients. There was an increased rate of flare
      defined by PGA during pregnancy (HR: 1.59; 95% CI 1.27 to 1.96); however, this
      effect was modified by hydroxychloroquine (HCQ) use, with the HR of flares in
      pregnancy compared with non-pregnant/non-postpartum periods estimated to be 1.83
      (95% CI 1.34 to 2.45) for patients with no HCQ use and 1.26 (95% CI 0.88 to 1.69)
      for patients with HCQ use. The risk of flare was similarly elevated among non-HCQ
      users in the 3 months postpartum, but not for women taking HCQ after delivery.
      CONCLUSIONS: Our study supports and extends previous findings that the incidence
      of flare is increased during pregnancy and within the 3 months postpartum.
      Continuing HCQ, however, appeared to mitigate the risk of flare during and after
      pregnancy.

PMID- 29463521
TI  - Recent advances in the management of childhood dental caries.

PMID- 29463520
TI  - Lipid profile and effect of statin treatment in pooled phase II and phase III
      baricitinib studies.
AB  - OBJECTIVES: Lipid profiles are altered by active disease in patients with
      rheumatoid arthritis (RA) and may be further modified by treatment with Janus
      kinase inhibitors and other disease-modifying antirheumatic drugs. METHODS: Lipid
      data were analysed from phase II and III studies of 4 mg (n=997) and 2 mg (n=479)
      oral baricitinib administered once daily in patients with moderate-to-severe
      active RA. Lipoprotein particle size and number and GlycA were evaluated with
      nuclear magnetic resonance in one phase III study. The effect of statin therapy
      on lipid levels was evaluated in patients on statins at baseline and in patients
      who initiated statins during the study. RESULTS: Treatment with baricitinib was
      associated with increased levels of total cholesterol, low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and
      triglycerides, but no significant change in LDL-C:HDL-C ratio. Lipid levels
      plateaued after 12 weeks of treatment. Baricitinib treatment increased large LDL
      and decreased small, dense LDL particle numbers and GlycA. Lipid changes from
      baseline were not significantly different between baseline statin users and non
      users. In patients who initiated statin therapy during the study, LDL-C,
      triglycerides (baricitinib 4 mg only) and apolipoprotein B decreased to pre
      baricitinib levels; HDL-C and apolipoprotein A-I levels remained elevated.
      CONCLUSIONS: Baricitinib was associated with increased LDL-C, HDL-C and
      triglyceride levels, but did not alter the LDL-C:HDL-C ratio. Evaluation of
      cardiovascular event rates during long-term treatment is warranted to further
      characterise these findings and their possible clinical implications. TRIAL
      REGISTRATION NUMBER: NCT00902486, NCT01469013, NCT01185353, NCT01721044,
      NCT01721057, NCT01711359, NCT01710358, NCT01885078.

PMID- 29463522
TI  - Question 1: Is it safe to use ivermectin in children less than five years of age
      and weighing less than 15 kg?

PMID- 29463523
TI  - Mild thyroid dysfunction in pregnancy and children's educational performance.

PMID- 29463524
TI  - Dietitians' advice is evidence based and scientific.

PMID- 29463525
TI  - Maternal thyroid function and child educational attainment: prospective cohort
      study.
AB  - OBJECTIVE: To determine if first trimester maternal thyroid dysfunction is a
      critical determinant of child scholastic performance and overall educational
      attainment. DESIGN: Prospective cohort study. SETTING: Avon Longitudinal Study of
      Parents and Children cohort in the UK. PARTICIPANTS: 4615 mother-child pairs with
      an available first trimester sample (median 10 weeks gestation, interquartile
      range 8-12). EXPOSURES: Free thyroxine, thyroid stimulating hormone, and thyroid
      peroxidase antibodies assessed as continuous measures and the seven clinical
      categories of maternal thyroid function. MAIN OUTCOME MEASURES: Five age-specific
      national curriculum assessments in 3580 children at entry stage assessment at 54
      months, increasing up to 4461 children at their final school assessment at age
      15. RESULTS: No strong evidence of clinically meaningful associations of first
      trimester free thyroxine and thyroid stimulating hormone levels with entry stage
      assessment score or Standard Assessment Test scores at any of the key stages was
      found. Associations of maternal free thyroxine or thyroid stimulating hormone
      with the total number of General Certificates of Secondary Education (GCSEs)
      passed (range 0-16) were all close to the null: free thyroxine, rate ratio per
      pmol/L 1.00 (95% confidence interval 1.00 to 1.01); and thyroid stimulating
      hormone, rate ratio 0.98 (0.94 to 1.02). No important relationship was observed
      when more detailed capped scores of GCSEs allowing for both the number and grade
      of pass or when language, mathematics, and science performance were examined
      individually or when all educational assessments undertaken by an individual from
      school entry to leaving were considered. 200 (4.3%) mothers were newly identified
      as having hypothyroidism or subclinical hypothyroidism and 97 (2.1%) subclinical
      hyperthyroidism or hyperthyroidism. Children of mothers with thyroid dysfunction
      attained an equivalent number of GCSEs and equivalent grades as children of
      mothers with euthyroidism. CONCLUSIONS: Maternal thyroid dysfunction in early
      pregnancy does not have a clinically important association with impaired child
      performance at school or educational achievement.

PMID- 29463526
TI  - Elevated Plasma Moxifloxacin Concentrations and SLCO1B1 g.-11187G>A Polymorphism
      in Adults with Pulmonary Tuberculosis.
AB  - Moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals
      and bactericidal activity against Mycobacterium tuberculosis However,
      moxifloxacin plasma concentrations are variable between patients. We evaluated
      whether human gene polymorphisms affect moxifloxacin plasma concentrations in
      tuberculosis patients from two geographic regions. We enrolled a convenience
      sample of 49 adults with drug-sensitive pulmonary tuberculosis from Africa and
      the United States enrolled in two treatment trials of moxifloxacin as part of
      multidrug therapy. Pharmacokinetic parameters were evaluated by noncompartmental
      techniques. Human single-nucleotide polymorphisms of transporter genes were
      evaluated by analysis of covariance (ANCOVA) on moxifloxacin exposure and the
      peak (maximum) concentration (Cmax). The moxifloxacin area under the
      concentration-time curve from 0 to 24 h (AUC0-24) and Cmax were significantly
      increased by the drug milligram-per-kilogram dosage and the genotype of variant
      g.-11187G>A in the SLCO1B1 gene (rs4149015) but not by geographic region. The
      median moxifloxacin AUC0-24 was 46% higher and the median Cmax was 30% higher in
      4 (8%) participants who had the SLCO1B1 g.-11187 AG genotype than in 45
      participants who had the wild-type GG genotype (median AUC0-24 from the model,
      34.4 versus 23.6 MUg . h/ml [P = 0.005, ANCOVA]; median Cmax from the model, 3.5
      versus 2.7 MUg/ml [P = 0.009, ANCOVA]). Because moxifloxacin exhibits
      concentration-dependent prolongation of human QTc intervals and prolonged QTc
      intervals are associated with cardiac arrhythmia, further study is needed to
      evaluate the risk associated with the SLCO1B1 g.-11187G>A variant. (This study
      has been registered at ClinicalTrials.gov under identifier NCT00164463.).

PMID- 29463527
TI  - A New Marker of Echinocandin Activity in an In Vitro
      Pharmacokinetic/Pharmacodynamic Model Correlates with an Animal Model of
      Aspergillus fumigatus Infection.
AB  - The lack of a quantifiable marker for echinocandin activity hinders in vitro
      pharmacokinetic/pharmacodynamic (PK/PD) studies for Aspergillus spp. We developed
      an in vitro PK/PD model simulating the pharmacokinetics of anidulafungin and
      assessing its pharmacodynamics against Aspergillus fumigatus with a new, easily
      quantifiable, sensitive, and reproducible marker. Two clinical A. fumigatus
      isolates previously used in animals (AZN8196 and V52-35) with identical
      anidulafungin EUCAST (0.03 MUg/ml) and CLSI (0.015 MUg/ml) minimal effective
      concentrations (MEC) and one isolate (strain AFU79728) with an MEC of >16 MUg/ml
      were tested in a two-compartment PK/PD dialysis/diffusion closed model containing
      a dialysis membrane (DM) tube inoculated with 103 CFU/ml. During anidulafungin
      exposure, two types of fungal forms were observed inside the DM tube: floating
      conidia that were quantified by cultures and aberrant mycelia that were
      quantified by the vertical height of the mycelia attached on the DM tube. No
      aberrant mycelia were found for the resistant isolate or in the drug-free
      controls. An in vitro exposure-effect relationship was similar to that found in
      animals using survival as an endpoint, with a free-drug area under the
      concentration-time curve from 0 to 24 h (fAUC0-24) associated with 50% of maximal
      activity of 2.21 (range, 1.81 to 2.71) mg . h/liter in vitro versus 2.62 (range,
      1.88 to 3.65) mg . h/liter in vivo (P = 0.41). The hillslopes were also similar,
      with 1.96 versus 1.34 (P = 0.29). Analysis of each isolate separately showed
      increased antifungal susceptibility between AZN8196 and V52-35 (P < 0.001) even
      though they have the same CLSI and EUCAST MECs, but the strains have two 2-fold
      dilutions lower MICs using Etest and the XTT {2,3-bis (2-methoxy-4-nitro-5
      sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide} method. Dose
      fractionation studies with all three echinocandins showed that their activities
      are best described by fAUC and not the maximum concentration of free drug
      (fCmax). The new marker correlated with in vivo outcome and can be used for in
      vitro PK/PD studies exploring the pharmacodynamics of echinocandins against
      Aspergillus spp.

PMID- 29463528
TI  - Optimization and Evaluation of Piperacillin-Tobramycin Combination Dosage
      Regimens against Pseudomonas aeruginosa for Patients with Altered
      Pharmacokinetics via the Hollow-Fiber Infection Model and Mechanism-Based
      Modeling.
AB  - Augmented renal clearance (ARC) in critically ill patients can result in
      suboptimal drug exposures and treatment failure. Combination dosage regimens
      accounting for ARC have never been optimized and evaluated against Pseudomonas
      aeruginosa by use of the hollow-fiber infection model (HFIM). Using a P.
      aeruginosa isolate from a critically ill patient and static-concentration time
      kill experiments (SCTKs), we studied clinically relevant piperacillin and
      tobramycin concentrations, alone and in combinations, against two inocula (105.8
      and 107.6 CFU/ml) over 72 h. We subsequently evaluated the effects of optimized
      piperacillin (4 g every 4 h [q4h], given as 0.5-h infusions) plus tobramycin (5
      mg/kg of body weight q24h, 7 mg/kg q24h, or 10 mg/kg q48h, given as 0.5-h
      infusions) regimens on killing and regrowth in the HFIM, simulating a creatinine
      clearance of 250 ml/min. Mechanism-based modeling was performed in S-ADAPT. In
      SCTKs, piperacillin plus tobramycin (except combinations with 8 mg/liter
      tobramycin and against the low inoculum) achieved synergistic killing (>=2 log10
      versus the most active monotherapy at 48 h and 72 h) and prevented regrowth.
      Piperacillin monotherapy (4 g q4h) in the HFIM provided 2.4-log10 initial killing
      followed by regrowth at 24 h and resistance emergence. Tobramycin monotherapies
      displayed rapid initial killing (>=5 log10 at 13 h) followed by extensive
      regrowth. As predicted by mechanism-based modeling, the piperacillin plus
      tobramycin dosage regimens were synergistic and provided >=5-log10 killing with
      resistance suppression over 8 days in the HFIM. Optimized piperacillin-tobramycin
      regimens provided significant bacterial killing and suppressed resistance
      emergence. These regimens appear to be highly promising for effective and early
      treatment, even in the near-worst-case scenario of ARC.

PMID- 29463530
TI  - Kelch Mutations in Plasmodium falciparum Protein K13 Do Not Modulate Dormancy
      after Artemisinin Exposure and Sorbitol Selection In Vitro.
AB  - Some Kelch mutations of the Plasmodium falciparum K13 protein confer increased
      survival to dihydroartemisinin (DHA)-treated ring-stage parasites. Here, we asked
      if K13 mutations affect a dormancy phenotype allowing parasites to survive DHA
      exposure and then sorbitol selection. Although recrudescence from dormancy
      differed between two distinct parasite lines, it was similar for isogenic lines
      carrying single-site substitutions in K13. Therefore, K13 mutations do not alter
      the DHA-sorbitol combined dormancy phenotype; rather, traits from other loci
      likely determine this phenotype.

PMID- 29463529
TI  - Complete Genome Sequencing of Acinetobacter baumannii Strain K50 Discloses the
      Large Conjugative Plasmid pK50a Encoding Carbapenemase OXA-23 and Extended
      Spectrum beta-Lactamase GES-11.
AB  - Multidrug-resistant (MDR) Acinetobacter baumannii strains appeared as serious
      emerging nosocomial pathogens in clinical environments and especially in
      intensive care units (ICUs). A. baumannii strain K50, recovered from a
      hospitalized patient in Kuwait, exhibited resistance to carbapenems and
      additionally to ciprofloxacin, chloramphenicol, sulfonamides, amikacin, and
      gentamicin. Genome sequencing revealed that the strain possesses two plasmids,
      pK50a (79.6 kb) and pK50b (9.5 kb), and a 3.75-Mb chromosome. A. baumannii K50
      exhibits an average nucleotide identity (ANI) of 99.98% to the previously
      reported Iraqi clinical isolate AA-014, even though the latter strain lacked
      plasmid pK50a. Strain K50 belongs to sequence type 158 (ST158) (Pasteur scheme)
      and ST499 (Oxford scheme). Plasmid pK50a is a member of the Aci6 (replication
      group 6 [RG6]) group of Acinetobacter plasmids and carries a conjugative transfer
      module and two antibiotic resistance gene regions. The transposon Tn2008 carries
      the carbapenemase gene blaOXA-23, whereas a class 1 integron harbors the
      resistance genes blaGES-11, aacA4, dfrA7, qacEDelta1, and sul1, conferring
      resistance to all beta-lactams and reduced susceptibility to carbapenems and
      resistance to aminoglycosides, trimethoprim, quaternary ammonium compounds, and
      sulfamethoxazole, respectively. The class 1 integron is flanked by MITEs
      (miniature inverted-repeat transposable elements) delimiting the element at its
      insertion site.

PMID- 29463531
TI  - Complete Sequence of the IncA/C1 Plasmid pCf587 Carrying blaPER-2 from
      Citrobacter freundii.
AB  - The blaPER-2-harboring plasmid pCf587 (191,541 bp) belongs to lineage IncA/C1 and
      is closely related to pRA1. It contains a large resistance island including the
      blaPER-2 gene between two copies of ISKox2-like elements, the toxin-antitoxin
      module pemK-pemI, several other resistance genes inserted within a Tn2
      transposon, a Tn21-like structure, and a class 1 integron. pCf587 belongs to
      sequence type 13 (ST13), a new plasmid multilocus sequence typing (pMLST) ST.

PMID- 29463532
TI  - PGI2 Is a Novel SGI1-Relative Multidrug-Resistant Genomic Island Characterized in
      Proteus mirabilis.
AB  - A novel 61,578-bp genomic island named Proteus genomic island 2 (PGI2) was
      characterized in Proteus mirabilis of swine origin in China. The 23.85-kb
      backbone of PGI2 is related to those of Salmonella genomic island 1 and
      Acinetobacter genomic island 1. The multidrug resistance (MDR) region of PGI2 is
      a complex class 1 integron containing 14 different resistance genes. PGI2 was
      conjugally mobilized in trans to Escherichia coli in the presence of a
      conjugative IncC helper plasmid.

PMID- 29463533
TI  - Complex Interplay between Sphingolipid and Sterol Metabolism Revealed by
      Perturbations to the Leishmania Metabolome Caused by Miltefosine.
AB  - With the World Health Organization reporting over 30,000 deaths and 200,000 to
      400,000 new cases annually, visceral leishmaniasis is a serious disease affecting
      some of the world's poorest people. As drug resistance continues to rise, there
      is a huge unmet need to improve treatment. Miltefosine remains one of the main
      treatments for leishmaniasis, yet its mode of action (MoA) is still unknown.
      Understanding the MoA of this drug and parasite response to treatment could help
      pave the way for new and more successful treatments for leishmaniasis. A novel
      method has been devised to study the metabolome and lipidome of Leishmania
      donovani axenic amastigotes treated with miltefosine. Miltefosine caused a
      dramatic decrease in many membrane phospholipids (PLs), in addition to amino acid
      pools, while sphingolipids (SLs) and sterols increased. Leishmania major
      promastigotes devoid of SL biosynthesis through loss of the serine palmitoyl
      transferase gene (DeltaLCB2) were 3-fold less sensitive to miltefosine than wild
      type (WT) parasites. Changes in the metabolome and lipidome of miltefosine
      treated L. major mirrored those of L. donovani A lack of SLs in the DeltaLCB2
      mutant was matched by substantial alterations in sterol content. Together, these
      data indicate that SLs and ergosterol are important for miltefosine sensitivity
      and, perhaps, MoA.

PMID- 29463534
TI  - Alginate Oligosaccharide-Induced Modification of the lasI-lasR and rhlI-rhlR
      Quorum-Sensing Systems in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa plays a major role in many chronic infections. Its ability
      to readily form biofilms contributes to its success as an opportunistic pathogen
      and its resistance/tolerance to antimicrobial/antibiotic therapy. A low-molecular
      weight alginate oligomer (OligoG CF-5/20) derived from marine algae has
      previously been shown to impair motility in P. aeruginosa biofilms and disrupt
      pseudomonal biofilm assembly. As these bacterial phenotypes are regulated by
      quorum sensing (QS), we hypothesized that OligoG CF-5/20 may induce alterations
      in QS signaling in P. aeruginosa QS regulation was studied by using
      Chromobacterium violaceum CV026 biosensor assays that showed a significant
      reduction in acyl homoserine lactone (AHL) production following OligoG CF-5/20
      treatment (>=2%; P < 0.05). This effect was confirmed by liquid chromatography
      mass spectrometry analysis of C4-AHL and 3-oxo-C12-AHL production (>=2%; P <
      0.05). Moreover, quantitative PCR showed that reduced expression of both the las
      and rhl systems was induced following 24 h of treatment with OligoG CF-5/20
      (>=0.2%; P < 0.05). Circular dichroism spectroscopy indicated that these
      alterations were not due to steric interaction between the AHL and OligoG CF
      5/20. Confocal laser scanning microscopy (CLSM) and COMSTAT image analysis
      demonstrated that OligoG CF-5/20-treated biofilms had a dose-dependent decrease
      in biomass that was associated with inhibition of extracellular DNA synthesis
      (>=0.5%; P < 0.05). These changes correlated with alterations in the
      extracellular production of the pseudomonal virulence factors pyocyanin,
      rhamnolipids, elastase, and total protease (P < 0.05). The ability of OligoG CF
      5/20 to modify QS signaling in P. aeruginosa PAO1 may influence critical
      downstream functions such as virulence factor production and biofilm formation.

PMID- 29463535
TI  - GRL-079, a Novel HIV-1 Protease Inhibitor, Is Extremely Potent against Multidrug
      Resistant HIV-1 Variants and Has a High Genetic Barrier against the Emergence of
      Resistant Variants.
AB  - We identified four novel nonpeptidic human immunodeficiency virus type 1 (HIV-1)
      protease inhibitors (PIs), GRL-078, -079, -077, and -058, containing an
      alkylamine at the C-5 position of P2 tetrahydropyrano-tetrahydrofuran (Tp-THF)
      and a P2' cyclopropyl (Cp) (or isopropyl)-aminobenzothiazole (Abt) moiety. Their
      50% effective concentrations (EC50s) were 2.5 to 30 nM against wild-type HIV-1NL4
      3, 0.3 to 6.7 nM against HIV-2EHO, and 0.9 to 90 nM against laboratory-selected
      PI-resistant HIV-1 and clinical HIV-1 variants resistant to multiple FDA-approved
      PIs (HIVMDR). GRL-078, -079, -077, and -058 also effectively blocked the
      replication of HIV-1 variants highly resistant to darunavir (DRV) (HIVDRVrp51),
      with EC50s of 38, 62, 61, and 90 nM, respectively, while four FDA-approved PIs
      examined (amprenavir, atazanavir, lopinavir [LPV], and DRV) had virtually no
      activity (EC50s of >1,000 nM) against HIVDRVrp51 Structurally, GRL-078, -079, and
      -058 form strong hydrogen bond interactions between Tp-THF modified at C-5 and
      Asp29/Asp30/Gly48 of wild-type protease, while the P2' Cp-Abt group forms strong
      hydrogen bonds with Asp30'. The Tp-THF and Cp-Abt moieties also have good
      nonpolar interactions with protease residues located in the flap region. For
      selection with LPV and DRV by use of a mixture of 11 HIVMDR strains (HIV11MIX),
      HIV11MIX became highly resistant to LPV and DRV over 13 to 32 and 32 to 41 weeks,
      respectively. However, for selection with GRL-079 and GRL-058, HIV11MIX failed to
      replicate at >0.08 MUM and >0.2 MUM, respectively. Thermal stability results
      supported the highly favorable anti-HIV-1 potency of GRL-079 as well as other
      PIs. The present data strongly suggest that the P2 Tp-THF group modified at C-5
      and the P2' Abt group contribute to the potent anti-HIV-1 profiles of the four
      PIs against HIV-1NL4-3 and a wide spectrum of HIVMDR strains.

PMID- 29463536
TI  - Promoter Variation and Gene Expression of mcr-1-Harboring Plasmids in Clinical
      Isolates of Escherichia coli and Klebsiella pneumoniae from a Chinese Hospital.
AB  - Next-generation sequencing of 6 mcr-1-harboring Escherichia coli and Klebsiella
      pneumoniae isolates collected from a tertiary care hospital in China revealed
      significant sequence variations in the regions flanking the mcr-1 gene. While
      sequence variations significantly affected the expression and promoter activity
      of mcr-1, the mcr-1 gene expression levels did not correlate with the in vitro
      colistin resistance levels, which warrants further in-depth investigations.

PMID- 29463537
TI  - Impact of Oral Fidaxomicin Administration on the Intestinal Microbiota and
      Susceptibility to Clostridium difficile Colonization in Mice.
AB  - Clostridium difficile infection (CDI), a common cause of hospital-acquired
      infections, typically occurs after disruption of the normal gut microbiome by
      broad-spectrum antibiotics. Fidaxomicin is a narrow-spectrum antibiotic that
      demonstrates a reduced impact on the normal gut microbiota and is approved for
      the treatment of CDI. To further explore the benefits of this property, we used a
      murine model to examine the effects of fidaxomicin versus vancomycin on gut
      microbiota and susceptibility to C. difficile colonization while tracking
      microbiota recovery over time. Mice were exposed to fidaxomicin or vancomycin by
      oral gavage for 3 days and subsequently challenged with C. difficile spores at
      predetermined time points up to 21 days postexposure to antibiotics. Fecal
      samples were subsequently collected for analysis. Twenty-four hours
      postchallenge, mice were euthanized and the colon contents harvested. The
      microbiota was characterized using 16S rRNA gene sequencing. All fidaxomicin
      exposed mice (except for one at day 8) were resistant to C. difficile
      colonization. However, 9 of 15 vancomycin-exposed mice were susceptible to C.
      difficile colonization until day 12. All vancomycin-exposed mice recovered
      colonization resistance by day 16. Bacterial diversity was similar prior to
      antibiotic exposure in both arms and decreased substantially after exposure. A
      shift in taxonomic structure and composition occurred after both exposures;
      however, the shift was greater in vancomycin-exposed than in fidaxomicin-exposed
      mice. In summary, compared with vancomycin, fidaxomicin exposure had less impact
      on microbiota composition, promoted faster microbial recovery, and had less
      impact on the loss of C. difficile colonization resistance.

PMID- 29463538
TI  - Relationship between Tolerance and Persistence Mechanisms in Acinetobacter
      baumannii Strains with AbkAB Toxin-Antitoxin System.
AB  - The molecular mechanisms of tolerance and persistence associated with several
      compounds in Acinetobacter baumannii clinical isolates are unknown. Using
      transcriptomic and phenotypic studies, we found a link between mechanisms of
      bacterial tolerance to chlorhexidine and the development of persistence in the
      presence of imipenem in an A. baumannii strain belonging to clinical clone ST-2
      (OXA-24 beta-lactamase and AbkAB toxin-antitoxin [TA] system carried in a
      plasmid). Interestingly, the strain A. baumannii ATCC 17978 (AbkAB TA system from
      plasmid) showed persistence in the presence of imipenem and chlorhexidine.

PMID- 29463539
TI  - Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug
      Resistant Tuberculosis in India.
AB  - We studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA),
      ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant
      tuberculosis (MDR-TB) who were being treated according to the Revised National TB
      Control Programme (RNTCP) guidelines in India. This observational,
      pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini
      Naidu Medical College, Agra, India, who were being treated with a 24-month daily
      regimen. Serial blood samples were collected after directly observed
      administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were
      undertaken according to validated methods by high-performance liquid
      chromatography. Adverse events were noted at 6 months of treatment. The peak
      concentration (Cmax) of LFX was significantly higher in female than male children
      (11.5 MUg/ml versus 7.3 MUg/ml; P = 0.017). Children below 12 years of age had
      significantly higher ETH exposure (area under the concentration-time curve from 0
      to 8 h [AUC0-8]) than those above 12 years of age (17.5 MUg/ml . h versus 9.4
      MUg/ml; P = 0.030). Multiple linear regression analysis showed significant
      influence of gender on Cmax of ETH and age on Cmax and AUC0-8 of CS. This is the
      first and only study from India reporting on the pharmacokinetics of LFX, ETH,
      PZA, and CS in children with MDR-TB treated in the Government of India program.
      More studies on the safety and pharmacokinetics of second-line anti-TB drugs in
      children with MDR-TB from different settings are required.

PMID- 29463540
TI  - Pharmacokinetics of Penicillin G in Preterm and Term Neonates.
AB  - Group B streptococci are common causative agents of early-onset neonatal sepsis
      (EOS). Pharmacokinetic (PK) data for penicillin G have been described for
      extremely preterm neonates but have been poorly described for late-preterm and
      term neonates. Thus, evidence-based dosing recommendations are lacking. We
      describe the PK of penicillin G in neonates with a gestational age (GA) of >=32
      weeks and a postnatal age of <72 h. Penicillin G was administered intravenously
      at a dose of 25,000 or 50,000 IU/kg of body weight every 12 h (q12h). At steady
      state, PK blood samples were collected prior to and at 5 min, 1 h, 3 h, 8 h, and
      12 h after injection. Noncompartmental PK analysis was performed with WinNonlin
      software. With those data in combination with data from neonates with a GA of
      <=28 weeks, we developed a population PK model using NONMEM software and
      performed probability of target attainment (PTA) simulations. In total, 16
      neonates with a GA of >=32 weeks were included in noncompartmental analysis. The
      median volume of distribution (V) was 0.50 liters/kg (interquartile range, 0.42
      to 0.57 liters/kg), the median clearance (CL) was 0.21 liters/h (interquartile
      range, 0.16 to 0.29 liters/kg), and the median half-life was 3.6 h (interquartile
      range, 3.2 to 4.3 h). In the population PK analysis that included 35 neonates, a
      two-compartment model best described the data. The final parameter estimates were
      10.3 liters/70 kg and 29.8 liters/70 kg for V of the central and peripheral
      compartments, respectively, and 13.2 liters/h/70 kg for CL. Considering the
      fraction of unbound penicillin G to be 40%, the PTA of an unbound drug
      concentration that exceeds the MIC for 40% of the dosing interval was >90% for
      MICs of <=2 mg/liter with doses of 25,000 IU/kg q12h. In neonates, regardless of
      GA, the PK parameters of penicillin G were similar. The dose of 25,000 IU/kg q12h
      is suggested for treatment of group B streptococcal EOS diagnosed within the
      first 72 h of life. (This study was registered with the EU Clinical Trials
      Register under EudraCT number 2012-002836-97.).

PMID- 29463541
TI  - Verapamil Targets Membrane Energetics in Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis kills more people than any other bacterial pathogen
      and is becoming increasingly untreatable due to the emergence of resistance.
      Verapamil, an FDA-approved calcium channel blocker, potentiates the effect of
      several antituberculosis (anti-TB) drugs in vitro and in vivo This potentiation
      is widely attributed to inhibition of the efflux pumps of M. tuberculosis,
      resulting in intrabacterial drug accumulation. Here, we confirmed and quantified
      verapamil's synergy with several anti-TB drugs, including bedaquiline (BDQ) and
      clofazimine (CFZ), but found that the effect is not due to increased
      intrabacterial drug accumulation. We show that, consistent with its in vitro
      potentiating effects on anti-TB drugs that target or require oxidative
      phosphorylation, the cationic amphiphile verapamil disrupts membrane function and
      induces a membrane stress response similar to those seen with other membrane
      active agents. We recapitulated these activities in vitro using inverted
      mycobacterial membrane vesicles, indicating a direct effect of verapamil on
      membrane energetics. We observed bactericidal activity against nonreplicating
      "persister" M. tuberculosis that was consistent with such a mechanism of action.
      In addition, we demonstrated a pharmacokinetic interaction whereby human
      equivalent doses of verapamil caused a boost of rifampin exposure in mice,
      providing a potential explanation for the observed treatment-shortening effect of
      verapamil in mice receiving first-line drugs. Our findings thus elucidate the
      mechanistic basis for verapamil's potentiation of anti-TB drugs in vitro and in
      vivo and highlight a previously unrecognized role for the membrane of M.
      tuberculosis as a pharmacologic target.

PMID- 29463542
TI  - Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled
      Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria.
AB  - Sulfadoxine-pyrimethamine with amodiaquine is recommended by the World Health
      Organization as seasonal malaria chemoprevention for children aged 3 to 59 months
      in the sub-Sahel regions of Africa. Suboptimal dosing in children may lead to
      treatment failure and increased resistance. Pooled individual patient data from
      four previously published trials on the pharmacokinetics of sulfadoxine and
      pyrimethamine in 415 pediatric and 386 adult patients were analyzed using
      nonlinear mixed-effects modeling to evaluate the current dosing regimen and, if
      needed, to propose an optimized dosing regimen for children under 5 years of age.
      The population pharmacokinetics of sulfadoxine and pyrimethamine were both best
      described by a one-compartment disposition model with first-order absorption and
      elimination. Body weight, age, and nutritional status (measured as the weight-for
      age Z-score) were found to be significant covariates. Allometric scaling with
      total body weight and the maturation of clearance in children by postgestational
      age improved the model fit. Underweight-for-age children were found to have 15.3%
      and 26.7% lower bioavailabilities of sulfadoxine and pyrimethamine, respectively,
      for each Z-score unit below -2. Under current dosing recommendations, simulation
      predicted that the median day 7 concentration was below the 25th percentile for a
      typical adult patient (50 kg) for sulfadoxine for patients in the weight bands of
      8 to 9, 19 to 24, 46 to 49, and 74 to 79 kg and for pyrimethamine for patients in
      the weight bands of 8 to 9, 14 to 24, and 42 to 49 kg. An evidence-based dosing
      regimen was constructed that would achieve sulfadoxine and pyrimethamine
      exposures in young children and underweight-for-age young children that were
      similar to those currently seen in a typical adult.

PMID- 29463543
TI  - Mesoscopic Energy Minimization Drives Pseudomonas aeruginosa Biofilm Morphologies
      and Consequent Stratification of Antibiotic Activity Based on Cell Metabolism.
AB  - Segregation of bacteria based on their metabolic activities in biofilms plays an
      important role in the development of antibiotic resistance. Mushroom-shaped
      biofilm structures, which are reported for many bacteria, exhibit topographically
      varying levels of multiple drug resistance from the cap of the mushroom to its
      stalk. Understanding the dynamics behind the formation of such structures can aid
      in design of drug delivery systems, antibiotics, or physical systems for removal
      of biofilms. We explored the development of metabolically heterogeneous
      Pseudomonas aeruginosa biofilms using numerical models and laboratory knockout
      experiments on wild-type and chemotaxis-deficient mutants. We show that
      chemotactic processes dominate the transformation of slender and hemispherical
      structures into mushroom structures with a signature cap. Cellular Potts model
      simulation and experimental data provide evidence that accelerated movement of
      bacteria along the periphery of the biofilm, due to nutrient cues, results in the
      formation of mushroom structures and bacterial segregation. Multidrug resistance
      of bacteria is one of the most threatening dangers to public health.
      Understanding the mechanisms of the development of mushroom-shaped biofilms helps
      to identify the multidrug-resistant regions. We decoded the dynamics of the
      structural evolution of bacterial biofilms and the physics behind the formation
      of biofilm structures as well as the biological triggers that produce them.
      Combining in vitro gene knockout experiments with in silico models showed that
      chemotactic motility is one of the main driving forces for the formation of
      stalks and caps. Our results provide physicists and biologists with a new
      perspective on biofilm removal and eradication strategies.

PMID- 29463544
TI  - Gene Expression of Pneumocystis murina after Treatment with Anidulafungin Results
      in Strong Signals for Sexual Reproduction, Cell Wall Integrity, and Cell Cycle
      Arrest, Indicating a Requirement for Ascus Formation for Proliferation.
AB  - The echinocandins are a class of antifungal agents that target beta-1,3-d-glucan
      (BG) biosynthesis. In the ascigerous Pneumocystis species, treatment with these
      drugs depletes the ascus life cycle stage, which contains BG, but large numbers
      of forms which do not express BG remain in the infected lungs. In the present
      study, the gene expression profiles of Pneumocystis murina were compared between
      infected, untreated mice and mice treated with anidulafungin for 2 weeks to
      understand the metabolism of the persisting forms. Almost 80 genes were
      significantly up- or downregulated. Like other fungi exposed to echinocandins,
      genes associated with sexual replication, cell wall integrity, cell cycle arrest,
      and stress comprised the strongest upregulated signals in P. murina from the
      treated mice. The upregulation of the P. murina beta-1,3-d-glucan endohydrolase
      and endo-1,3-glucanase was notable and may explain the disappearance of the
      existing asci in the lungs of treated mice since both enzymes can degrade BG. The
      biochemical measurement of BG in the lungs of treated mice and fluorescence
      microscopy with an anti-BG antibody supported the loss of BG. Downregulated
      signals included genes involved in cell replication, genome stability, and
      ribosomal biogenesis and function and the Pneumocystis-specific genes encoding
      the major surface glycoproteins (Msg). These studies suggest that P. murina
      attempted to undergo sexual replication in response to a stressed environment and
      was halted in any type of proliferative cycle, likely due to a lack of BG. Asci
      appear to be a required part of the life cycle stage of Pneumocystis, and BG may
      be needed to facilitate progression through the life cycle via sexual
      replication.

PMID- 29463545
TI  - Detection of TR34/L98H CYP51A Mutation through Passive Surveillance for Azole
      Resistant Aspergillus fumigatus in the United States from 2015 to 2017.
AB  - The emergence of azole-resistant Aspergillus fumigatus has become a clinical
      problem in many parts of the world. Several amino acid mutations in the azole
      target protein Cyp51Ap contribute to this resistance, with the most concerning
      being the environmentally derived TR34/L98H and TR46/Y121F/T289A mutations. Here,
      we performed passive surveillance to assess a sample of the A. fumigatus
      population in the United States for the presence of these mutations. We found
      1.4% of those isolates to exhibit elevated MIC via broth microdilution, and five
      of those isolates harbored the TR34/L98H mutation.

PMID- 29463547
TI  - Doctors' language tests: five minutes with Ceri Butler.

PMID- 29463548
TI  - Determinants of hematology-oncology trainees' postfellowship career pathways with
      a focus on nonmalignant hematology.
AB  - Nonmalignant hematologic conditions are extremely prevalent and contribute
      significantly to the global burden of disease. The US health care system may soon
      face a shortage of specialists in nonmalignant hematology. We sought to identify
      factors that lead hematology-oncology fellows to pursue (or not to pursue)
      careers in nonmalignant hematology. Cross-sectional, web-based survey distributed
      to 149 graduates of a hematology-oncology fellowship program at a large academic
      medical center between 1998 and 2016. Eighty-six out of 149 graduates responded
      (57.7%); most (59 [68.6%]) practice at an academic medical center. Respondents
      spend a mean of 61% of their time in clinical practice, 23.7% conducting
      research, 5.2% in education, and 5.2% in administration. Those in clinical
      practice spend a mean of 52.1% of their time in solid tumor oncology, 37.5% in
      hematologic malignancies, and 10% in nonmalignant hematology; only 1 spent >50%
      of time practicing nonmalignant hematology. Factors most significantly affecting
      choice of patient population included clinical experience during fellowship and
      intellectual stimulation of the patient population/disease type. Factors that
      could have most significantly influenced a decision to spend more time in
      nonmalignant hematology included increased exposure/access to role models and
      mentors and opportunities for better career growth/advancement. Fellowship
      graduates spend >50% of their time in clinical practice, but almost none spend a
      significant amount of time practicing nonmalignant hematology. Given the growing
      number of patients with nonmalignant hematologic conditions and a possible future
      provider shortage, medical trainees should be encouraged to pursue careers in
      nonmalignant hematology.

PMID- 29463546
TI  - Treatment with Atorvastatin Provides Additional Benefits to Imipenem in a Model
      of Gram-Negative Pneumonia Induced by Klebsiella pneumoniae in Mice.
AB  - The clinical pathogen Klebsiella pneumoniae is a relevant cause of nosocomial
      infections, and resistance to current treatment with carbapenem antibiotics is
      becoming a significant problem. Statins are inhibitors of 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) used for controlling plasma cholesterol
      levels. There is clinical evidence showing other effects of statins, including
      decrease of lung inflammation. In the current study, we show that pretreatment
      with atorvastatin markedly attenuated lung injury, which was correlated with a
      reduction in the cellular influx into the alveolar space and lungs and
      downmodulation of the production of proinflammatory mediators in the initial
      phase of infection in C57BL/6 mice with K. pneumoniae However, atorvastatin did
      not alter the number of bacteria in the lungs and blood of infected mice, despite
      decreasing local inflammatory response. Interestingly, mice that received
      combined treatment with atorvastatin and imipenem displayed better survival than
      mice treated with vehicle, atorvastatin, or imipenem alone. These findings
      suggest that atorvastatin could be an adjuvant in host-directed therapies for
      multidrug-resistant K. pneumoniae, based on its powerful pleiotropic
      immunomodulatory effects. Together with antimicrobial approaches, combination
      therapy with anti-inflammatory compounds could improve the efficiency of therapy
      during acute lung infections.

PMID- 29463549
TI  - Androgen Deprivation Therapy Potentiates the Efficacy of Vascular Targeted
      Photodynamic Therapy of Prostate Cancer Xenografts.
AB  - Purpose: WST11 vascular targeted photodynamic therapy (VTP) is a local ablation
      approach relying upon rapid, free radical-mediated destruction of tumor
      vasculature. A phase III trial showed that VTP significantly reduced disease
      progression when compared with active surveillance in patients with low-risk
      prostate cancer. The aim of this study was to identify a druggable pathway that
      could be combined with VTP to improve its efficacy and applicability to higher
      risk prostate cancer tumors.Experimental Design: Transcriptome analysis of VTP
      treated tumors (LNCaP-AR xenografts) was used to identify a candidate pathway for
      combination therapy. The efficacy of the combination therapy was assessed in mice
      bearing LNCaP-AR or VCaP tumors.Results: Gene set enrichment analysis identifies
      the enrichment of androgen-responsive gene sets within hours after VTP treatment,
      suggesting that the androgen receptor (AR) may be a viable target in combination
      with VTP. We tested this hypothesis in mice bearing LNCaP-AR xenograft tumors by
      using androgen deprivation therapy (ADT), degarelix, in combination with VTP.
      Compared with either ADT or VTP alone, a single dose of degarelix in concert with
      VTP significantly inhibited tumor growth. A sharp decline in serum prostate
      specific antigen (PSA) confirmed AR inhibition in this group. Tumors treated by
      VTP and degarelix displayed intense terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling staining 7 days after treatment, supporting an
      increased apoptotic frequency underlying the effect on tumor
      inhibition.Conclusions: Improvement of local tumor control following androgen
      deprivation combined with VTP provides the rationale and preliminary protocol
      parameters for clinical trials in patients presented with locally advanced
      prostate cancer. Clin Cancer Res; 24(10); 2408-16. (c)2018 AACR.

PMID- 29463550
TI  - Phase Ib Study of Glasdegib, a Hedgehog Pathway Inhibitor, in Combination with
      Standard Chemotherapy in Patients with AML or High-Risk MDS.
AB  - Purpose: This open-label, multicenter, dose-finding, phase Ib study (NCT01546038)
      evaluated the safety, pharmacokinetics, pharmacodynamics, and clinical activity
      of the novel Hedgehog pathway Smoothened inhibitor glasdegib (PF-04449913) in
      patients (N = 52) with acute myeloid leukemia (AML) or high-risk myelodysplastic
      syndrome (MDS).Experimental Design: Glasdegib 100 or 200 mg was administered
      orally, once daily in 28-day cycles, in combination with low-dose cytarabine (arm
      A) or decitabine (arm B) to newly diagnosed patients considered not suitable for
      standard induction chemotherapy, and in combination with cytarabine/daunorubicin
      (arm C) to fit patients. The study followed a standard 3+3 dose-escalation
      design. The primary endpoint was dose-limiting toxicity (DLT). Ten additional
      patients were enrolled in expansion cohorts of arms A (n = 23) and C (n = 22) to
      confirm the recommended phase II dose (RP2D).Results: No DLTs were observed in
      arms A and B; 1 DLT (grade 4 neuropathy) occurred in arm C. The most common
      treatment-related nonhematologic adverse events were mostly grades 1 and 2 in all
      arms. Muscle spasms, dysgeusia, and alopecia were generally mild. Overall, 16
      patients (31%) achieved a complete remission (CR)/CR with incomplete blood count
      recovery. Note that 100 mg daily was selected as the RP2D for glasdegib in
      combination with standard chemotherapies in the absence of an estimated MTD in
      this setting.Conclusions: Treatment with glasdegib in combination with standard
      chemotherapy was generally well-tolerated and consistent with prior findings,
      warranting further evaluation of glasdegib-based combinations in patients with
      AML or high-risk MDS. Clin Cancer Res; 24(10); 2294-303. (c)2018 AACR.

PMID- 29463551
TI  - Prediction of the Optimal Dosing Regimen Using a Mathematical Model of Tumor
      Uptake for Immunocytokine-Based Cancer Immunotherapy.
AB  - Purpose: Optimal dosing is critical for immunocytokine-based cancer immunotherapy
      to maximize efficacy and minimize toxicity. Cergutuzumab amunaleukin (CEA-IL2v)
      is a novel CEA-targeted immunocytokine. We set out to develop a mathematical
      model to predict intratumoral CEA-IL2v concentrations following various systemic
      dosing intensities.Experimental Design: Sequential measurements of CEA-IL2v
      plasma concentrations in 74 patients with solid tumors were applied in a series
      of differential equations to devise a model that also incorporates the peripheral
      concentrations of IL2 receptor-positive cell populations (i.e., CD8+, CD4+, NK,
      and B cells), which affect tumor bioavailability of CEA-IL2v. Imaging data from a
      subset of 14 patients were subsequently utilized to additionally predict antibody
      uptake in tumor tissues.Results: We created a pharmacokinetic/pharmacodynamic
      mathematical model that incorporates the expansion of IL2R-positive target cells
      at multiple dose levels and different schedules of CEA-IL2v. Model-based
      prediction of drug levels correlated with the concentration of IL2R-positive
      cells in the peripheral blood of patients. The pharmacokinetic model was further
      refined and extended by adding a model of antibody uptake, which is based on drug
      dose and the biological properties of the tumor. In silico predictions of our
      model correlated with imaging data and demonstrated that a dose-dense schedule
      comprising escalating doses and shortened intervals of drug administration can
      improve intratumoral drug uptake and overcome consumption of CEA-IL2v by the
      expanding population of IL2R-positive cells.Conclusions: The model presented here
      allows simulation of individualized treatment plans for optimal dosing and
      scheduling of immunocytokines for anticancer immunotherapy. Clin Cancer Res;
      24(14); 3325-33. (c)2018 AACRSee related commentary by Ruiz-Cerda et al., p.
      3236.

PMID- 29463552
TI  - Integrated Pharmacokinetic/Pharmacodynamic Model of a Bispecific CD3xCD123 DART
      Molecule in Nonhuman Primates: Evaluation of Activity and Impact of
      Immunogenicity.
AB  - Purpose: Flotetuzumab (MGD006 or S80880) is a bispecific molecule that recognizes
      CD3 and CD123 membrane proteins, redirecting T cells to kill CD123-expressing
      cells for the treatment of acute myeloid leukemia. In this study, we developed a
      mathematical model to characterize MGD006 exposure-response relationships and to
      assess the impact of its immunogenicity in cynomolgus monkeys.Experimental
      Design: Thirty-two animals received multiple escalating doses (100-300-600-1,000
      ng/kg/day) via intravenous infusion continuously 4 days a week. The model
      reflects sequential binding of MGD006 to CD3 and CD123 receptors. Formation of
      the MGD006/CD3 complex was connected to total T cells undergoing trafficking,
      whereas the formation of the trimolecular complex results in T-cell activation
      and clonal expansion. Activated T cells were used to drive the peripheral
      depletion of CD123-positive cells. Anti-drug antibody development was linked to
      MGD006 disposition as an elimination pathway. Model validation was tested by
      predicting the activity of MGD006 in eight monkeys receiving continuous 7-day
      infusions.Results: MGD006 disposition and total T-cell and CD123-positive cell
      profiles were well characterized. Anti-drug antibody development led to the
      suppression of T-cell trafficking but did not systematically abolish CD123
      positive cell depletion. Target cell depletion could persist after drug
      elimination owing to the self-proliferation of activated T cells generated during
      the first cycles. The model was externally validated with the 7-day infusion
      dosing schedule.Conclusions: A translational model was developed for MGD006 that
      features T-cell activation and expansion as a key driver of pharmacologic
      activity and provides a mechanistic quantitative platform to inform dosing
      strategies in ongoing clinical studies. Clin Cancer Res; 24(11); 2631-41. (c)2018
      AACR.

PMID- 29463553
TI  - Concurrent Inhibition of Neurosphere and Monolayer Cells of Pediatric
      Glioblastoma by Aurora A Inhibitor MLN8237 Predicted Survival Extension in PDOX
      Models.
AB  - Purpose: Pediatric glioblastoma multiforme (pGBM) is a highly aggressive tumor in
      need of novel therapies. Our objective was to demonstrate the therapeutic
      efficacy of MLN8237 (alisertib), an orally available selective inhibitor of
      Aurora A kinase (AURKA), and to evaluate which in vitro model system (monolayer
      or neurosphere) can predict therapeutic efficacy in vivoExperimental Design:
      AURKA mRNA expressions were screened with qRT-PCR. In vitro antitumor effects
      were examined in three matching pairs of monolayer and neurosphere lines
      established from patient-derived orthotopic xenograft (PDOX) models of the
      untreated (IC-4687GBM), recurrent (IC-3752GBM), and terminal (IC-R0315GBM)
      tumors, and in vivo therapeutic efficacy through log rank analysis of survival
      times in two models (IC-4687GBM and IC-R0315GBM) following MLN8237 treatment (30
      mg/kg/day, orally, 12 days). Drug concentrations in vivo and mechanism of action
      and resistance were also investigated.Results: AURKA mRNA overexpression was
      detected in 14 pGBM tumors, 10 PDOX models, and 6 cultured pGBM lines as compared
      with 11 low-grade gliomas and normal brains. MLN8237 penetrated into pGBM
      xenografts in mouse brains. Significant extension of survival times were achieved
      in IC-4687GBM of which both neurosphere and monolayer were inhibited in vitro,
      but not in IC-R0315GBM of which only neurosphere cells responded (similar to IC
      3752GBM). Apoptosis-mediated MLN8237 induced cell death, and the presence of
      AURKA-negative and CD133+ cells appears to have contributed to in vivo therapy
      resistance.Conclusions: MLN8237 successfully targeted AURKA in a subset of pGBMs.
      Our data suggest that combination therapy should aim at AURKA-negative and/or
      CD133+ pGBM cells to prevent tumor recurrence. Clin Cancer Res; 24(9); 2159-70.
      (c)2018 AACR.

PMID- 29463554
TI  - Combination Approach for Detecting Different Types of Alterations in Circulating
      Tumor DNA in Leiomyosarcoma.
AB  - Purpose: The clinical utility of circulating tumor DNA (ctDNA) monitoring has
      been shown in tumors that harbor highly recurrent mutations. Leiomyosarcoma
      represents a type of tumor with a wide spectrum of heterogeneous genomic
      abnormalities; thus, targeting hotspot mutations or a narrow genomic region for
      ctDNA detection may not be practical. Here, we demonstrate a combinatorial
      approach that integrates different sequencing protocols for the orthogonal
      detection of single-nucleotide variants (SNV), small indels, and copy-number
      alterations (CNA) in ctDNA.Experimental Design: We employed Cancer Personalized
      Profiling by deep Sequencing (CAPP-Seq) for the analysis of SNVs and indels,
      together with a genome-wide interrogation of CNAs by Genome Representation
      Profiling (GRP). We profiled 28 longitudinal plasma samples and 25 tumor
      specimens from 7 patients with leiomyosarcoma.Results: We detected ctDNA in 6 of
      7 of these patients with >98% specificity for mutant allele fractions down to a
      level of 0.01%. We show that results from CAPP-Seq and GRP are highly concordant,
      and the combination of these methods allows for more comprehensive monitoring of
      ctDNA by profiling a wide spectrum of tumor-specific markers. By analyzing
      multiple tumor specimens in individual patients obtained from different sites and
      at different times during treatment, we observed clonal evolution of these tumors
      that was reflected by ctDNA profiles.Conclusions: Our strategy allows for the
      comprehensive monitoring of a broad spectrum of tumor-specific markers in plasma.
      Our approach may be clinically useful not only in leiomyosarcoma but also in
      other tumor types that lack recurrent genomic alterations. Clin Cancer Res;
      24(11); 2688-99. (c)2018 AACR.

PMID- 29463555
TI  - Foretinib Overcomes Entrectinib Resistance Associated with the NTRK1 G667C
      Mutation in NTRK1 Fusion-Positive Tumor Cells in a Brain Metastasis Model.
AB  - Purpose: Rearrangement of the neurotrophic tropomyosin receptor kinase 1 (NTRK1)
      gene, which encodes tyrosine receptor kinase A (TRK-A), occurs in various
      cancers, including colon cancer. Although entrectinib is effective in the
      treatment of central nervous system (CNS) metastases that express NTRK1 fusion
      proteins, acquired resistance inevitably results in recurrence. The CNS is a
      sanctuary for targeted drugs; however, the mechanism by which CNS metastases
      become entrectinib-resistant remains elusive and must be clarified to develop
      better therapeutics.Experimental Design: The entrectinib-resistant cell line
      KM12SM-ER was developed by continuous treatment with entrectinib in the brain
      metastasis-mimicking model inoculated with the entrectinib-sensitive human colon
      cancer cell line KM12SM, which harbors the TPM3-NTRK1 gene fusion. The mechanism
      of entrectinib resistance in KM12SM-ER cells was examined by next-generation
      sequencing. Compounds that overcame entrectinib resistance were screened from a
      library of 122 kinase inhibitors.Results: KM12SM-ER cells, which showed moderate
      resistance to entrectinib in vitro, had acquired the G667C mutation in NTRK1 The
      kinase inhibitor foretinib inhibited TRK-A phosphorylation and the viability of
      KM12SM-ER cells bearing the NTRK1-G667C mutation in vitro Moreover, foretinib
      markedly inhibited the progression of entrectinib-refractory KM12SM-ER-derived
      liver metastases and brain tumors in animal models, predominantly through
      inhibition of TRK-A phosphorylation.Conclusions: These results suggest that
      foretinib may be effective in overcoming entrectinib resistance associated with
      the NTRK1-G667C mutation in NTRK1 fusion-positive tumors in various organs,
      including the brain, and provide a rationale for clinical trials of foretinib in
      cancer patients with entrectinib-resistant tumors harboring the NTRK1-G667C
      mutation, including patients with brain metastases. Clin Cancer Res; 24(10); 2357
      69. (c)2018 AACR.

PMID- 29463556
TI  - TGFbeta1 Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal
      Cancer Patients after Definitive Radiotherapy.
AB  - Purpose: TGFbeta1 plays a critical role in inflammation and immune responses and
      treatment response and survival. TGFbeta1 variants may affect its expression
      level or functional efficiency, thus modifying tumor status and survival in human
      papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx
      (SCCOP).Experimental Design: We determined tumor HPV16 status and genotyped three
      TGFbeta1 polymorphisms in 564 incident SCCOP patients treated with radiotherapy
      or chemoradiation. Univariate and multivariable Cox models were used to evaluate
      the associations between the three polymorphisms and survival.Results: Overall,
      85% of patients (482 of 564) had HPV16-positive SCCOP. We found that TGFbeta1
      rs1982073 had statistically significant associations with survival, whereas
      TGFbeta1 rs1800469 and TGFbeta1 rs1800471 did not. Patients with TGFbeta1
      rs1982073 CT/CC variant genotypes had significantly better overall, disease
      specific, and disease-free survival compared with those with the corresponding
      common homozygous TT genotype (all log-rank: P < 0.001). Furthermore, these
      genotypes were significantly associated with an approximately 5 times reduced
      risk of overall death, death owing to disease, and recurrence after multivariable
      adjustment. Moreover, the stratified analyses by tumor HPV status indicated that
      the significant effects of TGFbeta1 rs1982073 polymorphism on survival were found
      among HPV16-positive SCCOP patients only. Finally, the functional relevance of
      these variants was further characterized.Conclusions: Our findings support that
      the TGFbeta1 rs1982073 polymorphism plays a significant role in the prognosis of
      SCCOP, especially in HPV16-positive SCCOP patients treated with chemoradiation.
      Prospective studies with larger sample sizes are needed to confirm these
      findings. Clin Cancer Res; 24(9); 2225-33. (c)2018 AACR.

PMID- 29463557
TI  - The Airway Transcriptome as a Biomarker for Early Lung Cancer Detection.
AB  - Lung cancer remains the leading cause of cancer-related death due to its advanced
      stage at diagnosis. Early detection of lung cancer can be improved by better
      defining who should be screened radiographically and determining which imaging
      detected pulmonary nodules are malignant. Gene expression biomarkers measured in
      normal-appearing airway epithelium provide an opportunity to use lung cancer
      associated molecular changes in this tissue for early detection of lung cancer.
      Molecular changes in the airway may result from an etiologic field of injury
      and/or field cancerization. The etiologic field of injury reflects the aberrant
      physiologic response to carcinogen exposure that creates a susceptible
      microenvironment for cancer initiation. In contrast, field cancerization reflects
      effects of "first-hit" mutations in a clone of cells from which the tumor
      ultimately arises or the effects of the tumor on the surrounding tissue. These
      fields might have value both for assessing lung cancer risk and diagnosis. Cancer
      associated gene expression changes in the bronchial airway have recently been
      used to develop and validate a 23-gene classifier that improves the diagnostic
      yield of bronchoscopy for lung cancer among intermediate-risk patients. Recent
      studies have demonstrated that these lung cancer-related gene expression changes
      extend to nasal epithelial cells that can be sampled noninvasively. While the
      bronchial gene expression biomarker is being adopted clinically, further work is
      necessary to explore the potential clinical utility of gene expression profiling
      in the nasal epithelium for lung cancer diagnosis, lung cancer risk assessment,
      and precision medicine for lung cancer treatment and chemoprevention. Clin Cancer
      Res; 24(13); 2984-92. (c)2018 AACR.

PMID- 29463558
TI  - Disruption of Wnt/beta-Catenin Exerts Antileukemia Activity and Synergizes with
      FLT3 Inhibition in FLT3-Mutant Acute Myeloid Leukemia.
AB  - Purpose: Wnt/beta-catenin signaling is required for leukemic stem cell function.
      FLT3 mutations are frequently observed in acute myeloid leukemia (AML). Anomalous
      FLT3 signaling increases beta-catenin nuclear localization and transcriptional
      activity. FLT3 tyrosine kinase inhibitors (TKI) are used clinically to treat FLT3
      mutated AML patients, but with limited efficacy. We investigated the antileukemia
      activity of combined Wnt/beta-catenin and FLT3 inhibition in FLT3-mutant
      AML.Experimental Design: Wnt/beta-catenin signaling was inhibited by the beta
      catenin/CBP antagonist C-82/PRI-724 or siRNAs, and FLT3 signaling by sorafenib or
      quizartinib. Treatments on apoptosis, cell growth, and cell signaling were
      assessed in cell lines, patient samples, and in vivo in immunodeficient mice by
      flow cytometry, Western blot, RT-PCR, and CyTOF.Results: We found significantly
      higher beta-catenin expression in cytogenetically unfavorable and relapsed AML
      patient samples and in the bone marrow-resident leukemic cells compared with
      circulating blasts. Disrupting Wnt/beta-catenin signaling suppressed AML cell
      growth, induced apoptosis, abrogated stromal protection, and synergized with TKIs
      in FLT3-mutated AML cells and stem/progenitor cells in vitro The aforementioned
      combinatorial treatment improved survival of AML-xenografted mice in two in vivo
      models and impaired leukemia cell engraftment. Mechanistically, the combined
      inhibition of Wnt/beta-catenin and FLT3 cooperatively decreased nuclear beta
      catenin and the levels of c-Myc and other Wnt/beta-catenin and FLT3 signaling
      proteins. Importantly, beta-catenin inhibition abrogated the microenvironmental
      protection afforded the leukemic stem/progenitor cells.Conclusions: Disrupting
      Wnt/beta-catenin signaling exerts potent activities against AML stem/progenitor
      cells and synergizes with FLT3 inhibition in FLT3-mutant AML. These findings
      provide a rationale for clinical development of this strategy for treating FLT3
      mutated AML patients. Clin Cancer Res; 24(10); 2417-29. (c)2018 AACR.

PMID- 29463559
TI  - Capecitabine Efficacy Is Correlated with TYMP and RB1 Expression in PDX
      Established from Triple-Negative Breast Cancers.
AB  - Purpose: Triple-negative breast cancer (TNBC) patients with residual disease
      after neoadjuvant chemotherapy have a poor outcome. We developed patient-derived
      xenografts (PDX) from residual tumors to identify efficient chemotherapies and
      predictive biomarkers in a context of resistance to anthracyclines- and taxanes
      based treatments.Experimental Design: PDX were established from residual tumors
      of primary breast cancer patients treated in neoadjuvant setting. TNBC PDX were
      treated by anthracyclines, taxanes, platins, and capecitabine. Predictive
      biomarkers were identified by transcriptomic and immunohistologic analysis.
      Downregulation of RB1 was performed by siRNA in a cell line established from a
      PDX.Results: Residual TNBC PDX were characterized by a high tumor take, a short
      latency, and a poor prognosis of the corresponding patients. With the exception
      of BRCA1/2-mutated models, residual PDX were resistant to anthracyclines,
      taxanes, and platins. Capecitabine, the oral prodrug of 5-FU, was highly
      efficient in 60% of PDX, with two models showing complete responses. Prior
      treatment of a responder PDX with 5-FU increased expression of thymidylate
      synthase and decreased efficacy of capecitabine. Transcriptomic and IHC analyses
      of 32 TNBC PDX, including both residual tumors and treatment-naive derived
      tumors, identified RB1 and TYMP proteins as predictive biomarkers for
      capecitabine response. Finally, RB1 knockdown in a cell line established from a
      capecitabine-responder PDX decreased sensitivity to 5-FU treatment.Conclusions:
      We identified capecitabine as efficient chemotherapy in TNBC PDX models
      established from residual disease and resistant to anthracyclines, taxanes, and
      platins. RB1 positivity and high expression of TYMP were significantly associated
      with capecitabine response. Clin Cancer Res; 24(11); 2605-15. (c)2018 AACR.

PMID- 29463560
TI  - Molecular Lymph Node Status for Prognostic Stratification of Prostate Cancer
      Patients Undergoing Radical Prostatectomy with Extended Pelvic Lymph Node
      Dissection.
AB  - Purpose: Molecular lymph node (LN) analysis using quantitative polymerase chain
      reaction (qPCR) detects LN metastases with higher sensitivity than
      histopathology. However, the prognostic role of molecular LN status in prostate
      cancer patients treated with radical prostatectomy (RP) and extended pelvic LN
      dissection (ePLND) is unclear. To investigate the association of molecular
      compared with histopathologic LN status with biochemical recurrence.Experimental
      Design: Patients with intermediate and high-risk prostate cancer were
      prospectively enrolled and underwent RP with ePLND, including the obturator,
      internal, external, and the common iliac region. LNs >=3 mm were bisected and
      examined by standard histopathology and qPCR for Kallikrein3 (KLK3) expression.
      Biochemical recurrence was defined by confirmed postoperative PSA > 0.2
      ng/mL.Results: In 111 patients, 2,411 of 3,173 removed LNs were examined by both
      methods. Histopathology detected 68 LN metastases in 28 (25%) patients. Molecular
      analysis confirmed elevated KLK3 expression in 65 histopathologic LN metastases
      of all 28 pN1 patients (pN1/molN1) and additionally reclassified 224
      histopathologic negative LNs and 32 (29%) pN0 patients as LN-positive
      (pN0/molN1).At a median follow-up of 48 months, 52 (47%) patients developed
      biochemical recurrence. Median biochemical recurrence-free survival was 9 months
      [95% confidence interval (CI), 0.0-20.1] in pN1/molN1 patients, 24 months (95%
      CI, 1.7-46.3) in pN0/molN1 patients and was not reached in pN0/molN0 patients (P
      < 0.001). On multivariable Cox regression analysis, molecular LN status [HR 4.1
      (95% CI, 1.9-8.8), P < 0.001] but not histopathologic LN status [HR 1.5 (95% CI,
      0.8-3.0), P = 0.198] was confirmed as independent predictor of biochemical
      recurrence.Conclusions: Molecular LN analysis identified pN0 patients with a high
      risk of biochemical recurrence and provided superior prognostic information in
      comparison with histopathology alone. Clin Cancer Res; 24(10); 2342-9. (c)2018
      AACR.

PMID- 29463562
TI  - mTOR masters monocyte development in bone marrow by decreasing the inhibition of
      STAT5 on IRF8.
AB  - Monocytes and macrophages play a key role in defending pathogens, removing the
      dead cells or cell debris, and wound healing. The mammalian target of rapamycin
      (mTOR) inhibitor rapamycin (RPM) is widely used in clinics to treat patients with
      organ transplantation or tumors. The role of mTOR in monocyte/macrophage
      development remains to be clarified. Here we found that mTOR intrinsically
      controls monocyte/macrophage development, as evidenced by the decreased
      percentages and cell numbers of CD11b+F4/80+ cells resulting from mTOR inhibition
      in SCID mice, mTOR-deficient mice, and mixed chimera mice, and the in vitro
      colony formation and monocyte/macrophage induction assays. However, Lyzs-mTOR
      knockout mice displayed normal levels of monocytes/macrophages, indicating that
      mTOR is not essential for the survival and maturation of monocytes/macrophages.
      Further studies showed that mTOR deficiency significantly reduced macrophage
      colony-stimulating factor receptor CD115 expression at the transcriptional and
      translational levels. The molecular mechanism studies indicate that the impaired
      monocyte/macrophage development caused by mTOR deficiency is mainly a result of
      the overactivated STAT5 and subsequent downregulation of IRF8, but not the
      altered cell metabolism and autophagy. Therefore, our work identifies that mTOR
      is an intrinsic master for monocyte/macrophage development at the early stages
      through regulating STAT5-IRF8-dependent CD115-expressing pathway. Long-term usage
      of RPM may cause a defect of myeloid progenitors in bone marrow.

PMID- 29463561
TI  - Neutrophils provide cellular communication between ileum and mesenteric lymph
      nodes at graft-versus-host disease onset.
AB  - Conditioning-induced damage of the intestinal tract plays a critical role during
      the onset of acute graft-versus-host disease (GVHD). Therapeutic interference
      with these early events of GVHD is difficult, and currently used
      immunosuppressive drugs mainly target donor T cells. However, not donor T cells
      but neutrophils reach the sites of tissue injury first, and therefore could be a
      potential target for GVHD prevention. A detailed analysis of neutrophil fate
      during acute GVHD and the effect on T cells is difficult because of the short
      lifespan of this cell type. By using a novel photoconverter reporter system, we
      show that neutrophils that had been photoconverted in the ileum postconditioning
      later migrated to mesenteric lymph nodes (mLN). This neutrophil migration was
      dependent on the intestinal microflora. In the mLN, neutrophils colocalized with
      T cells and presented antigen on major histocompatibility complex (MHC)-II,
      thereby affecting T cell expansion. Pharmacological JAK1/JAK2 inhibition reduced
      neutrophil influx into the mLN and MHC-II expression, thereby interfering with an
      early event in acute GVHD pathogenesis. In agreement with this finding,
      neutrophil depletion reduced acute GVHD. We conclude that neutrophils are
      attracted to the ileum, where the intestinal barrier is disrupted, and then
      migrate to the mLN, where they participate in alloantigen presentation. JAK1/JAK2
      inhibition can interfere with this process, which provides a potential
      therapeutic strategy to prevent early events of tissue damage-related innate
      immune cell activation and, ultimately, GVHD.

PMID- 29463563
TI  - First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803
      to treat relapse after transplantation.
AB  - New therapies for patients with hematologic malignancies who relapse after
      allogeneic hematopoietic cell transplantation (allo-HCT) are needed. Interleukin
      15 (IL-15) is a cytokine that stimulates CD8+ T-cell and natural killer (NK) cell
      antitumor responses, and we hypothesized this cytokine may augment
      antileukemia/antilymphoma immunity in vivo. To test this, we performed a first-in
      human multicenter phase 1 trial of the IL-15 superagonist complex ALT-803 in
      patients who relapsed >60 days after allo-HCT. ALT-803 was administered to 33
      patients via the IV or subcutaneous (SQ) routes once weekly for 4 doses (dose
      levels of 1, 3, 6, and 10 MUg/kg). ALT-803 was well tolerated, and no dose
      limiting toxicities or treatment-emergent graft-versus-host disease requiring
      systemic therapy was observed in this clinical setting. Adverse events following
      IV administration included constitutional symptoms temporally related to
      increased serum IL-6 and interferon-gamma. To mitigate these effects, the SQ
      route was tested. SQ delivery resulted in self-limited injection site rashes
      infiltrated with lymphocytes without acute constitutional symptoms.
      Pharmacokinetic analysis revealed prolonged (>96 hour) serum concentrations
      following SQ, but not IV, injection. ALT-803 stimulated the activation,
      proliferation, and expansion of NK cells and CD8+ T cells without increasing
      regulatory T cells. Responses were observed in 19% of evaluable patients,
      including 1 complete remission lasting 7 months. Thus, ALT-803 is a safe, well
      tolerated agent that significantly increased NK and CD8+ T cell numbers and
      function. This immunostimulatory IL-15 superagonist warrants further
      investigation to augment antitumor immunity alone and combined with other
      immunotherapies. This trial was registered at www.clinicaltrials.gov as
      #NCT01885897.

PMID- 29463564
TI  - Glutaminolysis is a metabolic dependency in FLT3ITD acute myeloid leukemia
      unmasked by FLT3 tyrosine kinase inhibition.
AB  - FLT3 internal tandem duplication (FLT3ITD) mutations are common in acute myeloid
      leukemia (AML) associated with poor patient prognosis. Although new-generation
      FLT3 tyrosine kinase inhibitors (TKI) have shown promising results, the outcome
      of FLT3ITD AML patients remains poor and demands the identification of novel,
      specific, and validated therapeutic targets for this highly aggressive AML
      subtype. Utilizing an unbiased genome-wide clustered regularly interspaced short
      palindromic repeats (CRISPR)/Cas9 screen, we identify GLS, the first enzyme in
      glutamine metabolism, as synthetically lethal with FLT3-TKI treatment. Using
      complementary metabolomic and gene-expression analysis, we demonstrate that
      glutamine metabolism, through its ability to support both mitochondrial function
      and cellular redox metabolism, becomes a metabolic dependency of FLT3ITD AML,
      specifically unmasked by FLT3-TKI treatment. We extend these findings to AML
      subtypes driven by other tyrosine kinase (TK) activating mutations and validate
      the role of GLS as a clinically actionable therapeutic target in both primary AML
      and in vivo models. Our work highlights the role of metabolic adaptations as a
      resistance mechanism to several TKI and suggests glutaminolysis as a
      therapeutically targetable vulnerability when combined with specific TKI in
      FLT3ITD and other TK activating mutation-driven leukemias.

PMID- 29463566
TI  - Evaluating the Inpatient Pediatric Ethical Consultation Service.
AB  - OBJECTIVES: Pediatric ethical consultation services (ECSs) have been
      proliferating at medical centers, with little data available on evaluating their
      implementation. The objective of this study was to evaluate the pediatric ECS and
      understand the ethical issues occurring within a single quaternary-level
      pediatric hospital. METHODS: A retrospective chart review of documented ethics
      consultations at a large pediatric hospital from November 2010 to November 2013
      was performed and data was abstracted per the US Department of Veterans Affairs'
      Domains of Ethics in Health Care. An anonymous, prospective survey regarding
      ethical issues encountered was distributed electronically to ~3500 inpatient
      staff from November 2013 through January 2014. Ethical domains, demographics,
      feelings of distress by staff, and location of occurrence data were collected.
      These data were compared with formally documented ethics consults from the
      retrospective chart review and ECS activity during the same period. RESULTS: A
      total of 47 ethics consults were documented between 2010 and 2013, primarily in
      the domains of end-of-life care (19; 40%) and shared decision-making (17; 36%).
      Sixty-three staff members (92% female; 42% nurses; 20% attending physicians)
      logged an encountered ethical issue between November 2013 and January 2014,
      corresponding to only 5 documented ethics consults in the same time period.
      Domains included end-of-life care (18; 28.5%), shared decision-making (13;
      20.6%), everyday workplace (11; 17.4%), professionalism (8; 12.6%), and resource
      allocation (7; 11%). Eighty-one percent of subjects reported personal or
      professional distress. CONCLUSIONS: On the basis of this single-center study in
      which we reviewed formal documentation, we determined that formal pediatric ECSs
      are underused, particularly for ethical domains that cause staff members moral
      distress.

PMID- 29463565
TI  - An FGFR3/MYC positive feedback loop provides new opportunities for targeted
      therapies in bladder cancers.
AB  - FGFR3 alterations (mutations or translocation) are among the most frequent
      genetic events in bladder carcinoma. They lead to an aberrant activation of FGFR3
      signaling, conferring an oncogenic dependence, which we studied here. We
      discovered a positive feedback loop, in which the activation of p38 and AKT
      downstream from the altered FGFR3 upregulates MYC mRNA levels and stabilizes MYC
      protein, respectively, leading to the accumulation of MYC, which directly
      upregulates FGFR3 expression by binding to active enhancers upstream from FGFR3
      Disruption of this FGFR3/MYC loop in bladder cancer cell lines by treatment with
      FGFR3, p38, AKT, or BET bromodomain inhibitors (JQ1) preventing MYC transcription
      decreased cell viability in vitro and tumor growth in vivo A relevance of this
      loop to human bladder tumors was supported by the positive correlation between
      FGFR3 and MYC levels in tumors bearing FGFR3 mutations, and the decrease in FGFR3
      and MYC levels following anti-FGFR treatment in a PDX model bearing an FGFR3
      mutation. These findings open up new possibilities for the treatment of bladder
      tumors displaying aberrant FGFR3 activation.

PMID- 29463567
TI  - Single-molecule imaging reveals dynamic biphasic partition of RNA-binding
      proteins in stress granules.
AB  - Stress granules (SGs) are cytosolic, nonmembranous RNA-protein complexes. In
      vitro experiments suggested that they are formed by liquid-liquid phase
      separation; however, their properties in mammalian cells remain unclear. We
      analyzed the distribution and dynamics of two paradigmatic RNA-binding proteins
      (RBPs), Ras GTPase-activating protein SH3-domain-binding protein (G3BP1) and
      insulin-like growth factor II mRNA-binding protein 1 (IMP1), with single-molecule
      resolution in living neuronal cells. Both RBPs exhibited different exchange
      kinetics between SGs. Within SGs, single-molecule localization microscopy
      revealed distributed hotspots of immobilized G3BP1 and IMP1 that reflect the
      presence of relatively immobile nanometer-sized nanocores. We demonstrate
      alternating binding in nanocores and anomalous diffusion in the liquid phase with
      similar characteristics for both RBPs. Reduction of low-complexity regions in
      G3BP1 resulted in less detectable mobile molecules in the liquid phase without
      change in binding in nanocores. The data provide direct support for liquid
      droplet behavior of SGs in living cells and reveal transient binding of RBPs in
      nanocores. Our study uncovers a surprising disconnect between SG partitioning and
      internal diffusion and interactions of RBPs.

PMID- 29463569
TI  - Engaging in even a small amount of walking is associated with lower mortality in
      older adults.

PMID- 29463568
TI  - An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate
      in Caucasians from the GOLDN cohort.
AB  - Our understanding of genetic influences on the response of lipids to specific
      interventions is limited. In this study, we sought to elucidate effects of rare
      genetic variants on lipid response to a high-fat meal challenge and fenofibrate
      (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)
      cohort using an exome-wide sequencing-based association study. Our results showed
      that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly
      associated with fasting LDL cholesterol response to FFB (P = 1.24E-07),
      triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and
      triglyceride postprandial AUI response to FFB (P = 1.88E-06), respectively. We
      sought to replicate the association for SIPA1L2 in the Heredity and Phenotype
      Intervention (HAPI) Heart Study, which included a high-fat meal challenge but not
      FFB treatment. The associated rare variants in GOLDN were not observed in the
      HAPI Heart study, and thus the gene-based result was not replicated. For
      functional validation, we found that gene transcript level of SIPA1L2 is
      associated with triglyceride postprandial AUI (P < 0.05) in GOLDN. Our study
      suggests unique genetic mechanisms contributing to the lipid response to the high
      fat meal challenge and FFB therapy.

PMID- 29463570
TI  - Correction: Enzymatic lipid oxidation by eosinophils propagates coagulation,
      hemostasis, and thrombotic disease.

PMID- 29463571
TI  - Chemotherapy-induced peripheral neuropathy: highlighting unmet needs.

PMID- 29463572
TI  - FRAX tool underestimates the risk of osteoporotic fractures in mental disorders.

PMID- 29463574
TI  - In This Issue of Diabetes.

PMID- 29463573
TI  - Mutant p53 controls tumor metabolism and metastasis by regulating PGC-1alpha.
AB  - Mutant forms of p53 protein often possess protumorigenic functions, conferring
      increased survival and migration to tumor cells via their "gain-of-function"
      activity. Whether and how a common polymorphism in TP53 at amino acid 72
      (Pro72Arg; referred to here as P72 and R72) impacts this gain of function has not
      been determined. We show that mutant p53 enhances migration and metastasis of
      tumors through the ability to bind and regulate PGC-1alpha and that this
      regulation is markedly impacted by the codon 72 polymorphism. Tumor cells with
      the R72 variant of mutant p53 show increased PGC-1alpha function along with
      greatly increased mitochondrial function and metastatic capability. Breast
      cancers containing mutant p53 and the R72 variant show poorer prognosis compared
      with P72. The combined results reveal PGC-1alpha as a novel "gain-of-function"
      partner of mutant p53 and indicate that the codon 72 polymorphism influences the
      impact of mutant p53 on metabolism and metastasis.

PMID- 29463575
TI  - Closing in on the Mechanisms of Pulsatile Insulin Secretion.
AB  - Insulin secretion from pancreatic islet beta-cells occurs in a pulsatile fashion,
      with a typical period of ~5 min. The basis of this pulsatility in mouse islets
      has been investigated for more than four decades, and the various theories have
      been described as either qualitative or mathematical models. In many cases the
      models differ in their mechanisms for rhythmogenesis, as well as other less
      important details. In this Perspective, we describe two main classes of models:
      those in which oscillations in the intracellular Ca2+ concentration drive
      oscillations in metabolism, and those in which intrinsic metabolic oscillations
      drive oscillations in Ca2+ concentration and electrical activity. We then discuss
      nine canonical experimental findings that provide key insights into the mechanism
      of islet oscillations and list the models that can account for each finding.
      Finally, we describe a new model that integrates features from multiple earlier
      models and is thus called the Integrated Oscillator Model. In this model,
      intracellular Ca2+ acts on the glycolytic pathway in the generation of
      oscillations, and it is thus a hybrid of the two main classes of models. It alone
      among models proposed to date can explain all nine key experimental findings, and
      it serves as a good starting point for future studies of pulsatile insulin
      secretion from human islets.

PMID- 29463577
TI  - Evaluation of the quality of RNA extracted from archival FFPE glioblastoma and
      epilepsy surgical samples for gene expression assays.
AB  - AIMS: Histopathological tissue samples are being increasingly used as sources of
      nucleic acids in molecular pathology translational research. This study
      investigated the suitability of glioblastoma and control central nervous system
      (CNS) formalin-fixed paraffin embedded (FFPE) tissue-derived RNA for gene
      expression analyses. METHODS: Total RNA was extracted from control (temporal lobe
      resection tissue) and glioblastoma FFPE tissue samples. RNA purity (260/280
      ratios) was determined and RNA integrity number (RIN) analysis was performed. RNA
      was subsequently used for RT-qPCR for two reference genes, 18S and GAPDH.
      RESULTS: Reference gene expression was equivalent between control and
      glioblastoma tissue when using RNA extracted from FFPE tissue, which has key
      implications for biological normalisation for CNS gene expression studies. There
      was a significant difference between the mean RIN values of control and
      glioblastoma FFPE tissue. There was no significant correlation between 260/280 or
      RIN values versus total RNA yield. The age of the tissue blocks did not influence
      RNA yield, fragmentation or purity. There was no significant correlation between
      RIN or 260/280 ratios and mean qPCR cycle threshold for either reference gene.
      CONCLUSIONS: This study showed that routinely available CNS FFPE tissue is
      suitable for RNA extraction and downstream gene expression studies, even after 60
      months of storage. Substantial RNA fragmentation associated with glioblastoma and
      control FFPE tissue blocks did not preclude downstream RT-qPCR gene expression
      analyses. Cross validation with both archival and prospectively collated FFPE
      specimens is required to further demonstrate that CNS tissue blocks can be used
      in novel translational molecular biomarker studies.

PMID- 29463578
TI  - False-negative CALR mutation in a suspected myeloproliferative neoplasm:
      identification, resolution and corrective action.

PMID- 29463579
TI  - Characteristics and Prognosis in Women and Men With Type 1 Diabetes Undergoing
      Coronary Angiography: A Nationwide Registry Report.
AB  - OBJECTIVE: To describe sex aspects on extent of coronary artery disease (CAD) and
      prognosis in a contemporary population with type 1 diabetes. RESEARCH DESIGN AND
      METHODS: All patients undergoing coronary angiography, 2001-2013, included in the
      Swedish Coronary Angiography and Angioplasty Registry and the Swedish National
      Diabetes Register as type 1 diabetes were followed for mortality until 31
      December 2013. The coronary angiogram was classified into normal, one-vessel
      disease, two-vessel disease, three-vessel disease, and left main stem disease.
      RESULTS: In all, 2,776 patients (42% women) with mean age 58 years (SD 11) were
      followed for 7.2 years (SD 2.2). Diabetes duration was longer in women (37 +/- 14
      vs. 34 +/- 14 years in men; P < 0.001), who also had more retinopathy (68% vs.
      65%; P = 0.050), whereas microalbuminuria was less common (41% vs. 51%; P <
      0.001). Indications for coronary angiography did not substantially differ in
      women and men. The extent of CAD was somewhat less severe in women (normal
      angiogram 23.5% vs. 19.1%, three-vessel and left main stem disease 34.5% vs.
      40.4%; P = 0.002), whereas mortality did not differ (adjusted hazard ratio 1.03
      [95% CI 0.88-1.20]; P = 0.754). The standard mortality ratio for women the first
      year was 7.49 (5.73-9.62) and for men was 4.58 (3.60-5.74). CONCLUSIONS: In
      patients with type 1 diabetes admitted for coronary angiography, the extent of
      CAD was almost similar in women and men, and total long-term mortality did not
      differ. Type 1 diabetes was associated with higher mortality risk in women than
      in men when compared with the general population. These data support that type 1
      diabetes attenuates the cardiovascular risk difference seen in men and women in
      the general population.

PMID- 29463581
TI  - A Novel Mechanism for Activation of GLI1 by Nuclear SMO That Escapes Anti-SMO
      Inhibitors.
AB  - Small-molecule inhibitors of the Hedgehog (HH) pathway receptor Smoothened (SMO)
      have been effective in treating some patients with basal cell carcinoma (BCC),
      where the HH pathway is often activated, but many patients respond poorly. In
      this study, we report the results of investigations on PTCH1 signaling in the HH
      pathway that suggest why most patients with BCC respond poorly to SMO inhibitors.
      In immortalized human keratinocytes, PTCH1 silencing led to the generation of a
      compact, holoclone-like morphology with increased expression of SMO and the
      downstream HH pathway transcription factor GLI1. Notably, although siRNA
      silencing of SMO in PTCH1-silenced cells was sufficient to suppress GLI1
      activity, this effect was not phenocopied by pharmacologic inhibition of SMO,
      suggesting the presence of a second undefined pathway through which SMO can
      induce GLI1. Consistent with this possibility, we observed increased nuclear
      localization of SMO in PTCH1-silenced cells as mediated by a putative SMO
      nuclear/nucleolar localization signal [N(o)LS]. Mutational inactivation of the
      N(o)LS ablated this increase and suppressed GLI1 induction. Immunohistologic
      analysis of human and mouse BCC confirmed evidence of nuclear SMO, although the
      pattern was heterogeneous between tumors. In PTCH1-silenced cells, >80% of the
      genes found to be differentially expressed were unaffected by SMO inhibitors,
      including the putative BCC driver gene CXCL11. Our results demonstrate how PTCH1
      loss results in aberrant regulation of SMO-independent mechanisms important for
      BCC biology and highlights a novel nuclear mechanism of SMO-GLI1 signaling that
      is unresponsive to SMO inhibitors.Significance: This study describes novel
      noncanonical Hedgehog signaling, where SMO enters the nucleus to activate GLI1, a
      mode that is unaffected by SMO inhibitors, thus prompting re-evaluation of
      current BCC treatment as well as new potential therapies targeting nuclear SMO.
      Cancer Res; 78(10); 2577-88. (c)2018 AACR.

PMID- 29463580
TI  - Truncated Glioma-Associated Oncogene Homolog 1 (tGLI1) Mediates Mesenchymal
      Glioblastoma via Transcriptional Activation of CD44.
AB  - The molecular pathways driving mesenchymal glioblastoma (GBM) are still not well
      understood. We report here that truncated glioma-associated oncogene homolog 1
      (tGLI1) is a tumor-specific transcription factor that facilitates GBM growth, is
      enriched in the mesenchymal subtype of GBM and glioma stem cells (GSC), and
      promotes mesenchymal GSC by upregulating transcription of CD44. In an orthotopic
      GBM xenograft mouse model, tGLI1-overexpressing tumors grew more aggressively
      with increased proliferation and angiogenesis compared with control and GLI1
      overexpressing xenografts. tGLI1 was highly expressed in GBM clinical specimens
      but undetectable in normal brains, whereas GLI1 was expressed in both tissues. A
      tGLI1 activation signature (tGAS) correlated with glioma grade, tumor
      angiogenesis, and poor overall survival, and GBMs with high tGAS were enriched
      with mesenchymal GBM/GSC gene signatures. Neurospheres contained increased levels
      of tGLI1, but not GLI1, compared with the monolayer culture; mesenchymal GSC
      expressed more tGLI1 than proneural GSC. Ectopic tGLI1 expression enhanced the
      ability of mesenchymal GSC to yield neurospheres in vitro and to form tumors in
      mouse brains. Selective tGLI1 knockdown reduced neurosphere formation of GBM
      cells. tGLI1 bound to and transactivated the promoter of the CD44 gene, a marker
      and mediator for mesenchymal GSC, leading to its expression. Collectively, these
      findings advance our understanding of GBM biology by establishing tGLI1 as a
      novel transcriptional activator of CD44 and a novel mediator of mesenchymal GBM
      and GSC.Significance: These findings highlight the role of a tumor-specific gain
      of-function transcription factor tGLI1 in mesenchymal glioma stem cell
      maintenance and mesenchymal GBM growth. Cancer Res; 78(10); 2589-600. (c)2018
      AACR.

PMID- 29463582
TI  - Infant Hospitalizations and Mortality After Maternal Vaccination.
AB  - BACKGROUND: The Advisory Committee on Immunization Practices currently recommends
      pregnant women receive influenza and tetanus toxoid, reduced diphtheria toxoid,
      and acellular pertussis (Tdap) vaccines. There are limited studies of the long
      term safety in infants for vaccines administered during pregnancy. We evaluate
      whether maternal receipt of influenza and Tdap vaccines increases the risk of
      infant hospitalization or death in the first 6 months of life. METHODS: We
      included singleton, live birth pregnancies in the Vaccine Safety Datalink between
      2004 and 2014. Outcomes were infant hospitalizations and mortality in the first 6
      months of life. We performed a case-control study matching case patients and
      controls 1:1 and used conditional logistic regression to estimate odds ratios for
      maternal exposure to influenza and/or Tdap vaccines in pregnancy. RESULTS: There
      were 413 034 live births in our population. Of these, 25 222 infants had
      hospitalizations and 157 infants died in the first 6 months of life. We found no
      association between infant hospitalization and maternal influenza (adjusted odds
      ratio: 1.00; 95% confidence interval [CI]: 0.96-1.04) or Tdap (adjusted odds
      ratio: 0.94; 95% CI: 0.88-1.01) vaccinations. We found no association between
      infant mortality and maternal influenza (adjusted odds ratio: 0.96; 95% CI: 0.54
      1.69) or Tdap (adjusted odds ratio: 0.44; 95% CI: 0.17-1.13) vaccinations.
      CONCLUSIONS: We found no association between vaccination during pregnancy and
      risk of infant hospitalization or death in the first 6 months of life. These
      findings support the safety of current recommendations for influenza and Tdap
      vaccination during pregnancy.

PMID- 29463583
TI  - Alterations in placental long chain polyunsaturated fatty acid metabolism in
      human intrauterine growth restriction.
AB  - Fatty acids (FA) are critical for fetal brain development and are transferred
      across the placenta by membrane-bound FA transport proteins (FATP), translocases
      (FAT/CD36), and cytosolic binding proteins (FABP). The cytosolic protein
      perilipin-2 aids in neutral lipid storage within lipid droplets. Decreased
      placental nutrient transport is believed to contribute to intrauterine growth
      restriction (IUGR); however, IUGR placental lipid transport and metabolism are
      poorly understood. We hypothesized that protein expression of FATPs, FABPs, and
      perilipin-2 in human placenta is decreased and placental lipid content and
      incorporation into lipid classes are reduced in IUGR. Placental tissue of
      idiopathic IUGR (n=25) and gestational age-matched, appropriately grown for
      gestational age (AGA) fetuses (n=19) was collected. We determined protein
      expression of FABP4 and perilipin-2 in placental homogenate and FATPs (2, 4, 6,
      CD36) in syncytiotrophoblast microvillous plasma membrane (MVM) by Western blot.
      Lipid droplet area (Oil Red O stain) and cellular FA content (GC/MS) were
      measured in chorionic villous tissue. MVM expression of FATP6 and CD36 was
      significantly increased in IUGR. The concentrations of seven n-6 and n-3 species
      long chain polyunsaturated FAs (LCPUFA) were significantly increased in the
      triglyceride fraction in IUGR vs AGA placenta. In summary, MVM FATP6 and CD36
      protein expression is increased and LCPUFA are preferentially routed toward
      cellular storage in TG in the IUGR placenta, possibly to protect against
      oxidative stress associated with cellular FA accumulation. We speculate that
      these changes may be caused by impaired efflux of FA across the fetal-facing
      syncytiotrophoblast basal plasma membrane in IUGR placenta.

PMID- 29463585
TI  - Domestic violence: a cross-sectional study among pregnant women in different
      regions of Sri Lanka.
AB  - OBJECTIVES: The aims of this study were to assess the regional differences in
      domestic violence among pregnant women in the capital district and in the tea
      plantation sector of Sri Lanka, to explore potential contributory factors and to
      assess whether healthcare workers addressed domestic violence and disclosure
      among survivors. DESIGN: A cross-sectional study was carried out using
      interviewer-administered Abuse Assessment Screen. SETTING: Fifty-seven antenatal
      clinic centres in the capital district and 30 in the tea plantation sector.
      PARTICIPANTS: Pregnant women between 6 and 40 weeks of gestational age. In the
      capital district, 1375 women were recruited from antenatal clinic centres in the
      urban (n=25) and in the rural areas (n=32), and 800 women from 30 centres in the
      tea plantation sector. The response rate in the capital district was 95.6% and
      96.7% in the tea plantation sector. RESULTS: Among the total sample of pregnant
      women (n=2088), the prevalence of 'ever abused' was 38.6%, and the prevalence of
      'currently abused' was 15.9%. 'Ever abused' (31.5% vs 50.8%) and 'currently
      abused' (10% vs 25.8%) were significantly higher (P<0.001) among the women living
      in the tea plantation sector. 'Ever abused' was associated with living in the tea
      plantation sector, being employed, living far from gender-based violence care
      centre and of Muslim ethnicity, after adjusting for age, education and family
      income. Only 38.8% of all participants had been asked by healthcare workers about
      abuse. Living in the tea plantation sector and lower level of education were
      associated with not being asked. Among those who reported 'ever abused', only
      8.7% had disclosed the experience to a healthcare worker. CONCLUSION: Domestic
      violence was prevalent and highest among women in the tea plantation sector
      compared with the capital district. The capacity of healthcare workers in
      addressing domestic violence should be increased.

PMID- 29463584
TI  - Pregnancy diet and offspring asthma risk over a 10-year period: the Lifeways
      Cross Generation Cohort Study, Ireland.
AB  - OBJECTIVE: The association of maternal pregnancy diet with offspring asthma risk
      have been reported. However, literature on longitudinal patterns of asthma risk
      relative to intrauterine nutrient exposure is limited. We aimed to establish
      whether vegetable, oily fish and vitamin D intake during pregnancy are associated
      with childhood asthma risk over a 10-year period in the Irish Republic. DESIGN:
      Mother-child pairs (n=897) from the Lifeways prospective birth cohort, with data
      on nutrient intake during pregnancy and asthma status, respectively, were
      eligible for inclusion in the analysis. Data on socioeconomic and morbidity
      indicators over 10 years of follow-up on mothers and the index child were
      collected through self-administered questionnaires. Asthma status as diagnosed by
      the general practitioner at any time point over 10 years was related to maternal
      vegetable, oily fish and vitamin D intake during pregnancy, while adjusting for
      gestational age, socioeconomic status, smoking at delivery, breast feeding,
      season of birth and supplement use. Data were modelled with a marginal model on
      correlated observations over time within individuals. RESULTS: In the fully
      adjusted model, asthma was inversely associated with higher daily average intake
      of oily fish (OR 0.23 per serving/day, 95% CI 0.04 to 1.41) and of vegetables (OR
      0.96 per serving/day, 95% CI 0.88 to 1.05), but the confidence limits overlapped
      1. A higher daily vitamin D intake was associated with reduced odds of asthma (OR
      0.93 per MUg/day, 95% CI 0.89 to 0.98). CONCLUSION: This analysis suggests higher
      daily average intake of vitamin D in pregnancy is associated with asthma risk in
      offspring over the first 10 years of life.

PMID- 29463586
TI  - Evaluation of a complex intervention (Engager) for prisoners with common mental
      health problems, near to and after release: study protocol for a randomised
      controlled trial.
AB  - INTRODUCTION: The 'Engager' programme is a 'through-the-gate' intervention
      designed to support prisoners with common mental health problems as they
      transition from prison back into the community. The trial will evaluate the
      clinical and cost-effectiveness of the Engager intervention. METHODS AND
      ANALYSIS: The study is a parallel two-group randomised controlled trial with 1:1
      individual allocation to either: (a) the Engager intervention plus standard care
      (intervention group) or (b) standard care alone (control group) across two
      investigation centres (South West and North West of England). Two hundred and
      eighty prisoners meeting eligibility criteria will take part. Engager is a person
      centred complex intervention delivered by practitioners and aimed at addressing
      offenders' mental health and social care needs. It comprises one-to-one support
      for participants prior to release from prison and for up to 20 weeks postrelease.
      The primary outcome is change in psychological distress measured by the Clinical
      Outcomes in Routine Evaluation-Outcome Measure at 6 months postrelease. Secondary
      outcomes include: assessment of subjective met/unmet need, drug and alcohol use,
      health-related quality of life and well-being-related quality of life measured at
      3, 6 and 12 months postrelease; change in objective social domains, drug and
      alcohol dependence, service utilisation and perceived helpfulness of services and
      change in psychological constructs related to desistence at 6 and 12 months
      postrelease; and recidivism at 12 months postrelease. A process evaluation will
      assess fidelity of intervention delivery, test hypothesised mechanisms of action
      and look for unintended consequences. An economic evaluation will estimate the
      cost-effectiveness. ETHICS AND DISSEMINATION: This study has been approved by the
      Wales Research Ethics Committee 3 (ref: 15/WA/0314) and the National Offender
      Management Service (ref: 2015-283). Findings will be disseminated to
      commissioners, clinicians and service users via papers and presentations. TRIAL
      REGISTRATION NUMBER: ISRCTN11707331; Pre-results.

PMID- 29463587
TI  - Regional disparities in the intimate partner sexual violence rate against women
      in Parana State, Brazil, 2009-2014: an ecological study.
AB  - OBJECTIVE: Evaluate disparities in a Brazilian state by conducting an analysis to
      determine whether socioeconomic status was associated with the reported intimate
      partner sexual violence (IPSV) rates against women. DESIGN: A retrospective,
      ecological study. SETTINGS: Data retrieved from the Notifiable Diseases
      Information System database of the Ministry of Health of Brazil. PARTICIPANTS:
      All cases of IPSV (n=516) against women aged 15-49 years reported in the
      Notifiable Diseases Information System between 2009 and 2014. OUTCOME MEASURES:
      The data were evaluated through an exploratory analysis of spatial data. RESULTS:
      We identified a positive spatial self-correlation in the IPSV rate (0.7105,
      P<=0.001). Five high-high-type clusters were identified, predominantly in the
      Metropolitan, West, South Central, Southwest, Southeast and North Central
      mesoregions, with only one cluster identified in the North Pioneer mesoregion.
      Our findings also indicated that the associations between the IPSV rate and
      socioeconomic predictors (women with higher education, civil registry of legal
      separations, economically active women, demographic density and average female
      income) were significantly spatially non-stationary; thus, the regression
      coefficients verified that certain variables in the model were associated with
      the IPSV rate in some regions of the state. In addition, the geographically
      weighted regression (GWR) model improved the understanding of the associations
      between socioeconomic indicators and the IPSV notification rate, showing a better
      adjustment than the ordinary least square (OLS) model (OLS vs GWR model: R2: 0.95
      vs 0.99; Akaike information criterion: 4117.90 vs 3550.61; Moran's I: 0.0905 vs 
      0.0273, respectively). CONCLUSIONS: IPSV against women was heterogeneous in the
      state of Parana. The GWR model showed a better fit and enabled the analysis of
      the distribution of each indicator in the state, which demonstrated the utility
      of this model for the study of IPSV dynamics and the indication of local
      determinants of IPSV notification rates.

PMID- 29463588
TI  - Pathways and cost-effectiveness of routine lung cancer inpatient care in rural
      Anhui, China: a retrospective cohort study protocol.
AB  - INTRODUCTION: Routine inpatient care (RIC) for patients with cancer forms various
      pathways of clinical procedures. Although most individual procedures comprising
      the pathways have been tested via clinical trials, little is known about the
      collective cost and effectiveness of the pathways as a whole. This study aims at
      exploring RIC pathways for patients with lung cancer from rural Anhui, China, and
      their determinants and economic impacts. METHODS AND ANALYSIS: The study adopts a
      retrospective cohort design and proceeds in five steps. Step 1 defines the four
      main categories of study variables, including clinical procedures, direct cost
      and effectiveness of procedures, and factors affecting use of these procedures
      and their cost and effectiveness. Step 2 selects a cohort of 5000 patients with
      lung cancer diagnosed between 1 July 2015 and 30 June 2016 from rural Anhui by
      clustered random sampling. Step 3 retrieves the records of all the inpatient care
      episodes due to lung cancer and extracts data about RIC procedures, proximate
      variables (eg, Karnofsky Performance Status, Lung Function Score) of patient
      outcomes and related factors (eg, stage of cancer, age, gender), by two
      independent clinician researchers using a web-based form. Step 4 estimates the
      direct cost of each of the RIC procedures using micro-costing and collects data
      about ultimate patient outcomes (survival and progression-free survival) through
      a follow-up survey of patients and/or their close relatives. Step 5 analyses the
      data collected and explores pathways of RIC procedures and their relations with
      patient outcomes, costs, cost:effect ratios, and a whole range of clinical and
      sociodemographic factors using multivariate regression and path models. ETHICS
      AND DISSEMINATION: The study protocol has been approved by an authorised ethics
      committee of Anhui Medical University (reference number: 20170312). Findings from
      the study will be disseminated through conventional academic routes such as peer
      reviewed publications and presentations at regional, national and international
      conferences. TRIAL REGISTRATION NUMBER: ISRCTN25595562.

PMID- 29463589
TI  - Factors associated with insufficient awareness of breast cancer among women in
      Northern and Eastern China: a case-control study.
AB  - OBJECTIVES: To investigate the awareness and knowledge level of breast cancer
      among Chinese participants. DESIGN: Case-control study. SETTINGS: This study was
      based on the database of the minister-affiliated hospital key project of the
      Ministry of Health of the People's Republic of China that included 21 Chinese
      hospitals between April 2012 and April 2013. PARTICIPANTS: Matched study was
      designed among 2978 participants with Han ethnicity aged between 25 and 70.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Student's t-test, Pearson's chi2 test,
      reliability analysis, exploratory factor analysis, and univariate and
      multivariate logistic regression analyses were performed to know the level of
      breast cancer knowledge and find the breast cancer awareness-associated factors.
      RESULTS: 80.0% (2383/2978) of the participants had poor awareness level of breast
      cancer. In-depth knowledge of breast cancer such as early symptoms and risk
      factors was poorly found among them. Television broadcast and relatives or
      friends with breast cancers were the main sources of information about breast
      cancer. Of all participants, 72.8% (2167/2978) had heard about breast cancer as a
      frequent cancer affecting women, and 63.3% (1884/2978) knew that family history
      of breast cancer was a risk factor for breast cancer. Over half of them were
      aware that a breast lump could be a symptom of breast cancer. Multivariate
      analysis identified the following variables that predicted awareness of breast
      cancer: young age (OR=0.843, 95% CI 0.740 to 0.961), occupation (agricultural
      worker) (OR=12.831, 95% CI 6.998 to 23.523), high household social status
      (OR=0.644, 95% CI 0.531 to 0.780), breast hyperplasia history (OR=1.684, 95% CI
      1.273 to 2.228), high behavioural prevention score (OR=4.407, 95% CI 3.433 to
      5.657). CONCLUSION: Most women were aware of breast cancer as a disease, but
      their in-depth knowledge of it was poor. More publicity and education programmes
      to increase breast cancer awareness are necessary and urgent, especially for the
      ageing women and agricultural workers.

PMID- 29463590
TI  - Which patients benefit specifically from short-term psychodynamic psychotherapy
      (STPP) for depression? Study protocol of a systematic review and meta-analysis of
      individual participant data.
AB  - INTRODUCTION: Short-term psychodynamic psychotherapy (STPP) is an empirically
      supported treatment that is often used to treat depression. However, it is
      largely unclear if certain subgroups of depressed patients can benefit
      specifically from this treatment method. We describe the protocol for a
      systematic review and meta-analysis of individual participant data (IPD) aimed at
      identifying predictors and moderators of STPP for depression efficacy. METHOD AND
      ANALYSIS: We will conduct a systematic literature search in multiple
      bibliographic databases (PubMed, PsycINFO, Embase.com, Web of Science and
      Cochrane's Central Register of Controlled Trials), 'grey literature' databases
      (GLIN and UMI ProQuest) and a prospective trial register (http://www.controlled
      trials.com). We will include studies reporting (a) outcomes on standardised
      measures of (b) depressed (c) adult patients (d) receiving STPP. We will next
      invite the authors of these studies to share the participant-level data of their
      trials and combine these data to conduct IPD meta-analyses. The primary outcome
      for this study is post-treatment efficacy as assessed by a continuous depression
      measure. Potential predictors and moderators include all sociodemographic
      variables, clinical variables and psychological patient characteristics that are
      measured before the start of treatment and are assessed consistently across
      studies. One-stage IPD meta-analyses will be conducted using mixed-effects
      models. ETHICS AND DISSEMINATION: Institutional review board approval is not
      required for this study. We intend to submit reports of the outcomes of this
      study for publication to international peer-reviewed journals in the fields of
      psychiatry or clinical psychology. We also intend to present the outcomes at
      international scientific conferences aimed at psychotherapy researchers and
      clinicians. The findings of this study can have important clinical implications,
      as they can inform expectations of STPP efficacy for individual patients, and
      help to make an informed choice concerning the best treatment option for a given
      patient. PROSPERO REGISTRATION NUMBER: CRD42017056029.

PMID- 29463591
TI  - Optimising gestational weight gain and improving maternal and infant health
      outcomes through antenatal dietary, lifestyle and physical activity advice: the
      OPTIMISE randomised controlled trial protocol.
AB  - INTRODUCTION: Obesity represents a significant health burden, and WHO recognises
      the importance of preventing weight gain and subsequent development of obesity
      among adults who are within the healthy weight range. Women of reproductive age
      have demonstrated high rates of weight gain during pregnancy placing them at risk
      of becoming overweight or obese. We will evaluate the effects of dietary and
      physical activity advice on maternal, fetal and infant health outcomes, among
      pregnant women of normal body mass index (BMI). METHODS AND ANALYSIS: We will
      conduct a randomised controlled trial, consenting and randomising women with a
      live singleton pregnancy between 10+0 and 20+0 weeks and BMI 18.5-24.9 kg/m2 at
      first antenatal visit, from a tertiary maternity hospital. Women randomised to
      the Lifestyle Advice Group will receive three face-to-face sessions (two with a
      research dietitian and one with a trained research assistant) and three telephone
      calls over pregnancy, in which they will be provided with dietary and lifestyle
      advice and encouraged to make change using a SMART goals approach. Women
      randomised to the Standard Care Group will receive routine antenatal care. The
      primary outcome is infant birth weight >4 kg. Secondary outcomes will include
      adverse infant and maternal outcomes, maternal weight change, maternal diet and
      physical activity changes, maternal quality of life and emotional well-being,
      fetal growth and costs of healthcare. We will recruit 624 women to detect a
      reduction from 8.72% to 3.87% (alpha 0.05 (two-tailed); power 70%) in infants
      with birth weight >4 kg. Analyses will be intention to treat with estimates
      reported as relative risks and 95% CIs. ETHICS AND DISSEMINATION: Ethical
      approval has been obtained from the Women's and Children's Hospital ethics
      committee. Findings will be disseminated widely via journal publication and
      conference presentation(s), and participants informed of results. TRIAL
      REGISTRATION NUMBER: ACTRN12614000583640.

PMID- 29463592
TI  - Efficacy and safety of ginkgo preparations for attention deficit hyperactivity
      disorder: a systematic review protocol.
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most
      commonly diagnosed and treated childhood psychiatric disorders. The analogous
      diagnosis adopted in Europe is hyperkinetic disorder, which is defined in the
      WHO's International Classification of Diseases 10th edition (ICD-10).
      Hyperkinetic disorder includes more severe conditions. Ginkgo preparations are
      used in the treatment of ADHD. The present study will assess the efficacy and
      safety of ginkgo preparations in the treatment of ADHD in the currently published
      literature. MATERIALS AND METHODS: All prospective randomised controlled trials
      (RCTs) will be included in this systematic review. Patients diagnosed with ADHD
      according to American Psychiatric Association's Diagnostic and Statistical Manual
      of Mental Disorders fourth edition (DSM-IV), Diagnostic and Statistical Manual of
      Mental Disorders, fifth edition (DSM-5), ICD-10 or Chinese Classification and
      Diagnosis of Mental Diseases third edition (CMDD) will be included. A
      comprehensive search for RCTs to evaluate the effectiveness and tolerance of
      ginkgo preparations will be performed. The primary outcomes are the ADHD Rating
      Scale-IV and Revised Conners' Parent Rating Scale. The secondary outcomes are
      quality of life evaluated by the KINDL scale, adverse effects/events, Conners'
      Teacher Rating Scale, Strengths and Weaknesses of ADHD Symptoms and Normal
      Behaviour Scale and Fremdbeurteilungsbogen fur Hyperkinetische Storungen.
      Exclusion criteria are the following: (1) case reports, not randomised trial, non
      comparative studies and (2) patients who were not diagnosed based on DSM-IV, DSM
      5, ICD-10 or CMDD. The following databases will be searched from their inception
      until January 2018: Medline, Embase, the Cochrane Central Register of Controlled
      Trials, Web of Science, China Biology Medicine Disc, China National Knowledge
      Infrastructure Database, Wanfang Database and Chinese Scientific Journals
      Database. Two authors will independently perform the study selection, extract the
      data and assess the study quality and risk of bias. ETHICS AND DISSEMINATION:
      This systematic review does not require ethics approval. It will be published in
      a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017077190.

PMID- 29463593
TI  - Interleukin 33 Signaling Restrains Sporadic Colon Cancer in an Interferon-gamma
      Dependent Manner.
AB  - Interleukin 33 (IL33) is an inflammatory cytokine released during necrotic cell
      death. The epithelium and stroma of the intestine express large amounts of IL33
      and its receptor St2. IL33 is therefore continuously released during homeostatic
      turnover of the intestinal mucosa. Although IL33 can prevent colon cancer
      associated with inflammatory colitis, the contribution of IL33 signaling to
      sporadic colon cancer remains unknown. Here, we utilized a mouse model of
      sporadic colon cancer to investigate the contribution of IL33 signaling to
      tumorigenesis in the absence of preexisting inflammation. We demonstrated that
      genetic ablation of St2 enhanced colon tumor development. Conversely,
      administration of recombinant IL33 reduced growth of colon cancer cell
      allografts. In reciprocal bone marrow chimeras, the concurrent loss of IL33
      signaling within radioresistant nonhematopoietic, and the radiosensitive
      hematopoietic, compartments was associated with increased tumor burden. We
      detected St2 expression within the radioresistant mesenchymal cell compartment of
      the colon whose stimulation with IL33 induced expression of bona fide NF-kappaB
      target genes. Mechanistically, we discovered that St2 deficiency within the
      nonhematopoietic compartment coincided with increased abundance of regulatory T
      cells and suppression of an IFNgamma gene expression signature, whereas IL33
      administration triggered IFNgamma expression by tumor allograft-infiltrating T
      cells. The decrease of this IFNgamma gene expression signature was associated
      with more aggressive disease in human colon cancer patients, suggesting that lack
      of IL33 signaling impaired the generation of a potent IFNgamma-mediated antitumor
      immune response. Collectively, our data reveal that IL33 functions as a tumor
      suppressor in sporadic colon cancer. Cancer Immunol Res; 6(4); 409-21. (c)2018
      AACR.

PMID- 29463594
TI  - Another way of seeing things.
AB  - JGP study explores a novel photoreception pathway in a marine mollusk.

PMID- 29463596
TI  - Rest Easy with Intravenous Iron for Dialysis Patients? High Dose IV Iron Safety.

PMID- 29463595
TI  - Proteotranscriptomic Measurements of E6-Associated Protein (E6AP) Targets in
      DU145 Prostate Cancer Cells.
AB  - Prostate cancer is a common cause of cancer-related death in men. E6AP (E6
      Associated Protein), an E3 ubiquitin ligase and a transcription cofactor, is
      elevated in a subset of prostate cancer patients. Genetic manipulations of E6AP
      in prostate cancer cells expose a role of E6AP in promoting growth and survival
      of prostate cancer cells in vitro and in vivo However, the effect of E6AP on
      prostate cancer cells is broad and it cannot be explained fully by previously
      identified tumor suppressor targets of E6AP, promyelocytic leukemia protein and
      p27. To explore additional players that are regulated downstream of E6AP, we
      combined a transcriptomic and proteomic approach. We identified and quantified
      16,130 transcripts and 7,209 proteins in castration resistant prostate cancer
      cell line, DU145. A total of 2,763 transcripts and 308 proteins were
      significantly altered on knockdown of E6AP. Pathway analyses supported the known
      phenotypic effects of E6AP knockdown in prostate cancer cells and in parallel
      exposed novel potential links of E6AP with cancer metabolism, DNA damage repair
      and immune response. Changes in expression of the top candidates were confirmed
      using real-time polymerase chain reaction. Of these, clusterin, a stress-induced
      chaperone protein, commonly deregulated in prostate cancer, was pursued further.
      Knockdown of E6AP resulted in increased clusterin transcript and protein levels
      in vitro and in vivo Concomitant knockdown of E6AP and clusterin supported the
      contribution of clusterin to the phenotype induced by E6AP. Overall, results from
      this study provide insight into the potential biological pathways controlled by
      E6AP in prostate cancer cells and identifies clusterin as a novel target of E6AP.

PMID- 29463598
TI  - Management of Severe Hyponatremia with Continuous Renal Replacement Therapies.

PMID- 29463597
TI  - Safety of Intravenous Iron in Dialysis: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND OBJECTIVES: The safety of intravenous iron dosing in dialysis is
      uncertain. Higher-dose intravenous iron may be associated with a higher risk of
      infections, cardiovascular events, hospitalizations, and mortality. This
      systematic review aimed to determine the safety of higher-dose versus lower-dose
      intravenous iron, oral iron, or no iron supplementation in adult patients treated
      with dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We searched
      Medline, EMBASE, Cochrane library, and CINAHL from inception to January 6, 2017
      for randomized, controlled trials and observational studies comparing higher-dose
      intravenous iron with lower-dose intravenous iron, oral iron, or no iron in
      patients treated with dialysis that had all-cause mortality, infection,
      cardiovascular events, or hospitalizations as outcomes. RESULTS: Of the 2231
      eligible studies, seven randomized, controlled trials and 15 observational
      studies met inclusion criteria. The randomized, controlled trials showed no
      association between higher-dose intravenous iron (>400 mg/mo for most studies)
      and mortality (six studies; n=970; pooled relative risk, 0.93; 95% confidence
      interval, 0.47 to 1.84; follow-up ranging from 35 days to 26 months) or infection
      (four studies; n=743; relative risk, 1.02; 95% confidence interval, 0.74 to
      1.41). The observational studies showed no association between higher-dose
      intravenous iron (>200 mg/mo for most studies) and mortality (eight studies;
      n=241,408; hazard ratio, 1.09; 95% confidence interval, 0.98 to 1.21; follow-up
      ranging from 3 to 24 months), infection (eight studies; n=135,532; pooled hazard
      ratio, 1.13; 95% confidence interval, 0.99 to 1.28), cardiovascular events (seven
      studies; n=135,675; hazard ratio, 1.18; 95% confidence interval, 0.90 to 1.56),
      or hospitalizations (five studies; n=134,324; hazard ratio, 1.08; 95% confidence
      interval, 0.97 to 1.19). CONCLUSIONS: Higher-dose intravenous iron does not seem
      to be associated with higher risk of mortality, infection, cardiovascular events,
      or hospitalizations in adult patients on dialysis. Strength of this finding is
      limited by small numbers of participants and events in the randomized, controlled
      trials and statistical heterogeneity in observational studies.

PMID- 29463599
TI  - Why is life expectancy in England and Wales 'stalling'?
AB  - Several independent analyses, by both epidemiologists and actuaries, have
      concluded that the previous rate of improvement of life expectancy in England and
      Wales has now slowed markedly, and at older ages may even be reversing. However,
      although these findings have led the pension industry to reduce estimates of
      future liabilities, they have failed to elicit any significant concern in the
      Department of Health and Social Care. In this essay, we review the evidence on
      changing life expectancy, noting that the problems are greatest among older
      women. We then estimate the gap between what life expectancy is now and what it
      might have been had previous trends continued. At age 85, the gap is 0.34 years
      for women and 0.23 for men. We argue that recent changes cannot be dismissed as a
      temporary aberration. While the causes of this phenomenon are contested, there is
      growing evidence to point to the austerity policies implemented in recent years
      as at least a partial explanation. We conclude by calling for a fully independent
      enquiry to ascertain what is happening to life expectancy in England and Wales
      and what should be done about it.

PMID- 29463600
TI  - Transcriptional Landscape and Regulatory Roles of Small Noncoding RNAs in the
      Oxidative Stress Response of the Haloarchaeon Haloferax volcanii.
AB  - Haloarchaea in their natural environment are exposed to hypersalinity, intense
      solar radiation, and desiccation, all of which generate high levels of oxidative
      stress. Previous work has shown that haloarchaea are an order of magnitude more
      resistant to oxidative stress than most mesophilic organisms. Despite this
      resistance, the pathways haloarchaea use to respond to oxidative stress damage
      are similar to those of nonresistant organisms, suggesting that regulatory
      processes might be key to their robustness. Recently, small regulatory noncoding
      RNAs (sRNAs) were discovered in Archaea under a variety of environmental
      conditions. We report here the transcriptional landscape and functional roles of
      sRNAs in the regulation of the oxidative stress response of the model
      haloarchaeon Haloferax volcanii Thousands of sRNAs, both intergenic and
      antisense, were discovered using strand-specific sRNA sequencing (sRNA-seq),
      comprising 25 to 30% of the total transcriptome under no-challenge and oxidative
      stress conditions, respectively. We identified hundreds of differentially
      expressed sRNAs in response to hydrogen peroxide-induced oxidative stress in H.
      volcanii The targets of a group of antisense sRNAs decreased in expression when
      these sRNAs were upregulated, suggesting that sRNAs are potentially playing a
      negative regulatory role on mRNA targets at the transcript level. Target
      enrichment of these antisense sRNAs included mRNAs involved in transposon
      mobility, chemotaxis signaling, peptidase activity, and transcription
      factors.IMPORTANCE While a substantial body of experimental work has been done to
      uncover the functions of small regulatory noncoding RNAs (sRNAs) in gene
      regulation in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are
      still poorly understood. This study is the first to establish the regulatory
      effects of sRNAs on mRNAs during the oxidative stress response in the
      haloarchaeon Haloferax volcanii Our work demonstrates that common principles for
      the response to a major cellular stress exist across the 3 domains of life while
      uncovering pathways that might be specific to the Archaea This work also
      underscores the relevance of sRNAs in adaptation to extreme environmental
      conditions.

PMID- 29463601
TI  - Discovery of Calcium as a Biofilm-Promoting Signal for Vibrio fischeri Reveals
      New Phenotypes and Underlying Regulatory Complexity.
AB  - Vibrio fischeri uses biofilm formation to promote symbiotic colonization of its
      squid host, Euprymna scolopes Control over biofilm formation is exerted at the
      level of transcription of the symbiosis polysaccharide (syp) locus by a complex
      set of two-component regulators. Biofilm formation can be induced by
      overproduction of the sensor kinase RscS, which requires the activities of the
      hybrid sensor kinase SypF and the response regulator SypG and is negatively
      regulated by the sensor kinase BinK. Here, we identify calcium as a signal that
      promotes biofilm formation by biofilm-competent strains under conditions in which
      biofilms are not typically observed (growth with shaking). This was true for RscS
      overproducing cells as well as for strains in which only the negative regulator
      binK was deleted. The latter results provided, for the first time, an opportunity
      to induce and evaluate biofilm formation without regulator overexpression. Using
      these conditions, we determined that calcium induces both syp-dependent and
      bacterial cellulose synthesis (bcs)-dependent biofilms at the level of
      transcription of these loci. The calcium-induced biofilms were dependent on SypF,
      but SypF's Hpt domain was sufficient for biofilm formation. These data suggested
      the involvement of another sensor kinase(s) and led to the discovery that both
      RscS and a previously uncharacterized sensor kinase, HahK, functioned in this
      pathway. Together, the data presented here reveal both a new signal and biofilm
      phenotype produced by V. fischeri cells, the coordinate production of two
      polysaccharides involved in distinct biofilm behaviors, and a new regulator that
      contributes to control over these processes.IMPORTANCE Biofilms, or communities
      of surface-attached microorganisms adherent via a matrix that typically includes
      polysaccharides, are highly resistant to environmental stresses and are thus
      problematic in the clinic and important to study. Vibrio fischeri forms biofilms
      to colonize its symbiotic host, making this organism useful for studying
      biofilms. Biofilm formation depends on the syp polysaccharide locus and its
      regulators. Here, we identify a signal, calcium, that induces both SYP-PS and
      cellulose-dependent biofilms. We also identify a new syp regulator, the sensor
      kinase HahK, and discover a mutant phenotype for the sensor kinase RscS. This
      work thus reveals a specific biofilm-inducing signal that coordinately controls
      two polysaccharides, identifies a new regulator, and clarifies the regulatory
      control over biofilm formation by V. fischeri.

PMID- 29463602
TI  - Roger Hendrix: Gentle Provocateur.
AB  - Roger W. Hendrix was at the forefront of bacteriophage biology for nearly 50
      years and was central to our understanding of both viral capsid assembly and
      phage genomic diversity and evolution. Roger's warm and gentle demeanor belied a
      razor-sharp mind and warmed him to numerous highly productive collaborations that
      amplified his scientific impact. Roger was always completely open with scientific
      ideas while at the same time quietly agitating with a stream of new ways of
      thinking about problems and nudging our communities to search for innovative
      solutions: a gentle but highly effective provocateur.

PMID- 29463603
TI  - Membrane curvature and the Tol-Pal complex determine polar localization of the
      chemoreceptor Tar in E. coli.
AB  - Chemoreceptors are localized at the cell poles of Escherichia coli and other rod
      shaped bacteria. Over the years different mechanisms have been put forward to
      explain this polar localization; from stochastic clustering, membrane curvature
      driven localization, interactions with the Tol-Pal complex, to nucleoid
      exclusion. To evaluate these mechanisms, we monitored the cellular localization
      of the aspartate chemoreceptor Tar in different deletion mutants. We did not find
      any indication for either stochastic cluster formation or nucleoid exclusion.
      However, the presence of a functional Tol-Pal complex appeared to be essential to
      retain Tar at cell poles. Interestingly, Tar still accumulated at midcell in tol
      and in pal deletion mutants. In these mutants, the protein appears to gather at
      the base of division septa, a region characterised by strong membrane curvature.
      Chemoreceptors, like Tar, form trimer-of-dimers that bend the cell membrane due
      to a rigid tripod structure. The curvature approaches the curvature of the cell
      membrane generated during cell division, and localization of chemoreceptor
      tripods at curved membrane areas is therefore energetically favourable as it
      lowers membrane tension. Indeed, when we introduced mutations in Tar that abolish
      the rigid tripod structure, the protein was no longer able to accumulate at
      midcell or cell poles. These findings favour a model where chemoreceptor
      localization in E. coli is driven by strong membrane curvature and association
      with the Tol-Pal complex.Importance Bacteria have exquisite mechanisms to sense
      and to adapt to the environment they live in. One such mechanism involves the
      chemotaxis signal transduction pathway, in which chemoreceptors specifically bind
      certain attracting or repelling molecules and transduce the signals to the cell.
      In different rod-shaped bacteria, these chemoreceptors localize specifically to
      cell poles. Here, we examined the polar localization of the aspartate
      chemoreceptor Tar in E. coli, and found that membrane curvature at cell division
      sites and the Tol-Pal protein complex, localize Tar at cell division sites, the
      future cell poles. This study shows how membrane curvature can guide localization
      of proteins in a cell.

PMID- 29463604
TI  - Regeneration of Escherichia coli from Minicells through Lateral Gene Transfer.
AB  - Recently, artificial life has been created with artificial materials and methods.
      Life can be created when genomic DNA molecules are integrated in liposomes
      containing biochemical reactions for biogenic needs. However, it is not yet known
      whether the integration of these parts will be able to occur in nature and
      constitute a living system. I planned to regenerate bacteria from biologically
      active liposomes by inserting genomic DNA using only natural materials and
      methods. Minicells of Escherichia coli, containing plasmids and activated SOS
      proteins, act as protocells. Four new E. coli strains were regenerated from
      minicells by inserting the genomes by using the system for conjugation between F-
      and Hfr strains. Cells of the four regenerated strains showed the same genetic
      markers as the two genome donors. Pulse-field gel electrophoresis of their
      genomes showed admixing of those of both donors. In addition, the genomes of the
      four regenerated strains had chimeric genome of the two donors. These results
      show that synthesis of life can occur in nature without artificial
      arrangement.IMPORTANCE What is the difference between inanimate objects and
      organisms? Organisms always have genomic DNA. When organisms lose their genomes,
      they can neither grow nor reproduce. As the result, organisms turn into inanimate
      objects without their genomes. In this study, I regenerated microbes from cells
      that had lost their genomes (cell corpses) by inserting another genome. All steps
      of regeneration used the natural behavior of microbes. The same regeneration of
      microbes could happen in nature. These primitive lives have plasticity, which
      accelerates evolution and provides various kinds of life in the world.

PMID- 29463605
TI  - Phenazines regulate Nap-dependent denitrification in Pseudomonas aeruginosa
      biofilms.
AB  - Microbes in biofilms face the challenge of substrate limitation. In particular,
      cells in Pseudomonas aeruginosa biofilms growing in the laboratory or during host
      colonization often become limited for oxygen. Previously we found that
      phenazines, antibiotics produced by P. aeruginosa, balance the intracellular
      redox state for cells in biofilms. Here, we show that genes involved in
      denitrification are induced in phenazine-null (Deltaphz) mutant biofilms grown
      under an aerobic atmosphere, even in the absence of nitrate. This finding
      suggests that resident cells employ a bet-hedging strategy to anticipate the
      potential availability of nitrate and counterbalance their highly reduced redox
      state. Consistent with our previous characterization of aerobically-grown
      colonies supplemented with nitrate, we find that the pathway that is induced in
      Deltaphz colonies combines the nitrate reductase activity of the periplasmic
      enzyme Nap with downstream reduction of nitrite to nitrogen gas catalyzed by the
      enzymes Nir, Nor, and Nos. This regulatory relationship differs from the
      denitrification pathway that functions under anaerobic growth with nitrate as the
      terminal electron acceptor, which depends on the membrane-associated nitrate
      reductase Nar. We identify sequences in the promoter regions of the nap and nir
      operons that are required for the effects of phenazines on expression. We also
      show that specific phenazines have differential effects on nap gene expression.
      Finally, we provide evidence that individual steps of the denitrification pathway
      are catalyzed at different depths within aerobically grown biofilms, suggesting
      metabolic cross-feeding between community subpopulations.IMPORTANCE An
      understanding of the unique physiology of cells in biofilms is critical to our
      ability to treat fungal and bacterial infections. Colony biofilms of the
      opportunistic pathogen Pseudomonas aeruginosa, grown under an aerobic atmosphere
      but without nitrate, express a denitrification pathway that differs from that
      used for anaerobic growth. We report that the components of this pathway are
      induced by electron acceptor limitation and that they are differentially
      expressed over biofilm depth. These observations suggest that (i) P. aeruginosa
      exhibits "bet hedging" in that it expends energy and resources to prepare for
      nitrate availability when other electron acceptors are absent; and (ii) that
      cells in distinct biofilm microniches may be able to exchange substrates to
      catalyze full denitrification.

PMID- 29463606
TI  - Functional Analyses of the RsmY and RsmZ Small Noncoding Regulatory RNAs in
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen with distinct
      acute and chronic virulence phenotypes. Whereas acute virulence is typically
      associated with expression of a type III secretion system (T3SS), chronic
      virulence is characterized by biofilm formation. Many of the phenotypes
      associated with acute and chronic virulence are inversely regulated by RsmA and
      RsmF. RsmA and RsmF are both members of the CsrA family of RNA-binding proteins
      and regulate protein synthesis at the posttranscriptional level. RsmA activity is
      controlled by two small noncoding regulatory RNAs (RsmY and RsmZ). Bioinformatic
      analyses suggest that RsmY and RsmZ each have 3 or 4 putative RsmA binding sites.
      Each predicted binding site contains a GGA sequence presented in the loop portion
      of a stem-loop structure. RsmY and RsmZ regulate RsmA, and possibly RsmF, by
      sequestering these proteins from target mRNAs. In this study, we used selective
      2'-hydroxyl acylation analyzed by primer extension and mutational profiling
      (SHAPE-MaP) chemistry to determine the secondary structures of RsmY and RsmZ and
      functional assays to characterize the contribution of each GGA site to RsmY/RsmZ
      activity. Our data indicate that RsmA has two preferential binding sites on RsmY
      and RsmZ, while RsmF has one preferential binding site on RsmY and two sites on
      RsmZ. Despite RsmF and RsmA sharing a common consensus site, RsmF binding
      properties are more restrictive than those of RsmA.IMPORTANCE CsrA homologs are
      present in many bacteria. The opportunistic pathogen Pseudomonas aeruginosa uses
      RsmA and RsmF to inversely regulate factors associated with acute and chronic
      virulence phenotypes. RsmA has an affinity for RsmY and RsmZ higher than that of
      RsmF. The goal of this study was to understand the differential binding
      properties of RsmA and RsmF by using the RsmY and RsmZ regulatory small RNAs
      (sRNAs) as a model. Mutagenesis of the predicted RsmA/RsmF binding sites on RsmY
      and RsmZ revealed similarities in the sites required to control RsmA and RsmF
      activity in vivo Whereas binding by RsmA was relatively tolerant of binding site
      mutations, RsmF was sensitive to disruption to all but two of the sites, further
      demonstrating that the requirements for RsmF binding activity in vivo and in
      vitro are more stringent than those for RsmA.

PMID- 29463607
TI  - Reduced atherosclerosis lesion size, inflammatory response in miR-150 knockout
      mice via macrophage effects.
AB  - Atherosclerosis is considered to be a chronic inflammatory disease that can lead
      to severe clinically important cardiovascular events. miR-150 is a small
      noncoding RNA that significantly enhances inflammatory responses by upregulating
      endothelial cell proliferation and migration, as well as intravascular
      environmental homeostasis. However, the exact role of miR-150 in atherosclerosis
      remains unknown. Here, we investigated the effect of miR-150 deficiency on
      atherosclerosis development. Using double-knockout (miR-150-/- and ApoE-/-) mice,
      we measured atherosclerotic lesion size and stability. Meanwhile, we conducted in
      vivo bone marrow transplantation to identify cellular-level components of the
      inflammatory response. Compared with mice deficient only in ApoE, the double
      knockout mice had significantly smaller atherosclerotic lesions and displayed an
      attenuated inflammatory response. Moreover, miR-150 ablation promoted plaque
      stabilization via increases in smooth muscle cell and collagen content and
      decreased macrophage infiltration and lipid accumulation. The in vitro
      experiments indicated that an inflammatory response with miR-150 deficiency in
      atherosclerosis results directly from upregulated expression of the cytoskeletal
      protein, PDZ and LIM domain 1 (PDLIM1), in macrophages. More importantly, the
      decreases in phosphorylated p65 expression and inflammatory cytokine secretion
      induced by miR-150 ablation were reversed by PDLIM1 knockdown. These findings
      suggest that miR-150 is a promising target for the management of atherosclerosis.

PMID- 29463608
TI  - Generation and Characterization of a Novel Small Biologic Alternative to
      Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Antibodies, DS-9001a,
      Albumin Binding Domain-Fused Anticalin Protein.
AB  - Since it was recently reported that an antibody for proprotein convertase
      subtilisin/kexin type 9 (PCSK9) reduces the risk of cardiovascular events in a
      clinical context, PCSK9 inhibition is thought to be an attractive therapy for
      dyslipidemia. In the present study, we created a novel small biologic alternative
      to PCSK9 antibodies called DS-9001a, comprising an albumin binding domain fused
      to an artificial lipocalin mutein (ABD-fused Anticalin protein), which can be
      produced by a microbial production system. DS-9001a strongly interfered with
      PCSK9 binding to low-density-lipoprotein receptor (LDL-R) and PCSK9-mediated
      degradation of LDL-R. In cynomolgus monkeys, single DS-9001a administration
      significantly reduced the serum LDL-C level up to 21 days (62.4% reduction at the
      maximum). Moreover, DS-9001a reduced plasma non-high-density-lipoprotein
      cholesterol and oxidized LDL levels, and their further reductions were observed
      when atorvastatin and DS-9001a were administered in combination in human
      cholesteryl ester transfer protein/ApoB double transgenic mice. Additionally,
      their reductions on the combination of atorvastatin and DS-9001a were more
      pronounced than those on the combination of atorvastatin and anacetrapib. Besides
      its favorable pharmacologic profile, DS-9001a has a lower molecular weight (about
      22 kDa), yielding a high stoichiometric drug concentration that might result in a
      smaller administration volume than that in existing antibody therapy. Since
      bacterial production systems are viewed as more suited to mass production at low
      cost, DS-9001a may provide a new therapeutic option to treat patients with
      dyslipidemia. In addition, considering the growing demand for antibody-like
      drugs, ABD-fused Anticalin proteins could represent a promising new class of
      small biologic molecules.

PMID- 29463609
TI  - Outcomes after sudden cardiac arrest in sports centres with and without on-site
      external defibrillators.
AB  - OBJECTIVE: Sudden cardiac arrest (SCA) is a rare but tragic event during amateur
      sports activities. Our aim is to analyse whether availability of automated
      external defibrillators (AEDs) in amateur sports centres could impact on SCA
      survival. METHODS: This is an observational study. During an 18-year period, data
      regarding exercise-related SCA in sports centres were prospectively collected.
      Survival rates and time to response were compared between centres with an AED
      already available and centres where an AED was not already present. RESULTS: Out
      of 252 sports facilities, 207 (82%) acquired an AED during follow-up while 45
      (18%) did not. From 1999 to 2014, there were 26 SCAs (24 (92%) men, 54+/-17 years
      old) with 15 (58%) of them in centres with on-site AED. Neurologically intact
      survival rates were 93% in centres with on-site AED and 9% in centres without
      (P<0.001). Presence of on-site AED, presence of shockable rhythm, first
      assistance by a lay bystander and time to defibrillation were all related to
      neurological intact survival, but the presence of on-site AED was the only
      independent predictor in the multivariate analysis. The use of on-site AED
      resulted in a lower time to first shock when compared with emergency medical
      system-delivered AED (3.3+/-1.4min vs 7.3+/-3.2 min; P=0.001). CONCLUSIONS: The
      presence of on-site AEDs is associated with neurologically intact survival after
      an exercise-related SCA. Continuous efforts are recommended in order to introduce
      AEDs in sports and fitness centres, implement educational programmes and increase
      common awareness about SCA.

PMID- 29463610
TI  - Impact of frequent premature ventricular contractions on pregnancy outcomes.
AB  - OBJECTIVES: To determine cardiac and fetal/neonatal event rates among pregnant
      women with premature ventricular contractions (PVCs) and compare with control
      groups. METHODS: Prospective case-control cohort study: 53 consecutive
      pregnancies in 49 women referred to the St. Paul's Hospital between 2010 and 2016
      with PVC burden >1% in women without underlying cardiac disease. Maternal cardiac
      and fetal/neonatal outcomes were compared with two pregnant control groups: (1)
      supraventricular tachycardia (SVT) group of 53 women referred for a history of
      SVT/SVT in the current pregnancy and (2) low-risk group of 53 women with no
      cardiac disease. RESULTS: The maximal PVC burden was 9.2% (range 1.1%-58.7%). Six
      of 53 (11%) pregnancies were complicated by a maternal cardiac event: heart
      failure n=1 and sustained ventricular tachycardia requiring therapy n=5 as
      compared with no cardiac events in both control groups. All women with an adverse
      event had a PVC burden >5%. Seven (13%) pregnancies were complicated by an
      adverse fetal and/or neonatal event and this was similar to the normal control
      group (5 (9%), P=0.45) and significantly less than the SVT group (16 (30%),
      P=0.03). The adverse fetal event was driven by small for gestational age neonates
      and preterm delivery. CONCLUSIONS: In our cohort of pregnant women with a
      structurally normal heart and 'high' PVC burden, we found an adverse maternal
      event rate of 11%, and all events were successfully managed with medical therapy.
      The rate of adverse fetal events in the PVC group was similar to the normal
      control group.

PMID- 29463611
TI  - Evidence for reduced susceptibility to cardiac bradycardias in South Asians
      compared with Caucasians.
AB  - OBJECTIVES: To investigate ethnic differences in susceptibility to bradycardias
      in South Asian and white European patients in the UK by determining rates of
      permanent pacemaker (PPM) implantation for sinus node dysfunction (SND) and
      atrioventricular block (AVB) in each ethnic group. METHODS: We carried out a
      retrospective cohort study into new PPM implantation during the period from 1 May
      2006 to 31 March 2014, in patients of South Asian and Caucasian ethnicity
      resident in Leicestershire, UK. Numbers of individuals at risk in each ethnic
      group were derived from UK National Census data of 2011. Crude, and age
      standardised incidence rates and risk ratios per 1000 population of PPM
      implantation were calculated for Caucasians and South Asians. RESULTS: During the
      study period, 4883 individuals from the Leicestershire population of 980 328
      underwent PPM implantation, a cumulative implantation rate of 4.98/1000
      population. The population cumulative PPM implantation rate for SND was
      1.74/1000, AVB 2.83/1000 and other indications 0.38/1000 population. The crude
      incidence in Caucasians (6.15/1000 population) was higher than in South Asians
      (1.07/1000 population) and remained higher after age standardisation (5.60/1000
      vs 2.03/1000, P<0.001). The age-standardised cumulative PPM implantation rates
      were lower in South Asians for both SND (0.53/1000 in South Asians; 1.97/1000 in
      Caucasians, P<0.001) and AVB (1.30/1000 in South Asians; 3.17/1000 in Caucasians,
      P<0.001). Standardised risk ratios (95% CI) for PPM implantation in South Asians
      compared with Caucasians for all pacing indications, SND and AVB were 0.36 (95%
      CI 0.36 to 0.37), 0.27 (95% CI 0.27 to 0.28) and 0.41 (95% CI 0.41 to 0.42),
      respectively. CONCLUSIONS: Rates of PPM implantation are lower in South Asians
      residing in the UK, compared with Caucasians. This observation raises the
      possibility of lower inherent susceptibility to bradycardias in South Asians
      compared with Caucasians. Studies aimed at identifying underlying mechanisms,
      including possible genetic differences, are warranted.

PMID- 29463612
TI  - Long-term impact of chronic total occlusion recanalisation in patients with ST
      elevation myocardial infarction.
AB  - BACKGROUND: During primary percutaneous coronary intervention (PCI), a concurrent
      chronic total occlusion (CTO) is found in 10% of patients with ST-elevation
      myocardial infarction (STEMI). Long-term benefits of CTO-PCI have been suggested;
      however, randomised data are lacking. Our aim was to determine mid-term and long
      term clinical outcome of CTO-PCI versus CTO-No PCI in patients with STEMI with a
      concurrent CTO. METHODS: The Evaluating Xience and left ventricular function in
      PCI on occlusiOns afteR STEMI (EXPLORE) was a multicentre randomised trial that
      included 302 patients with STEMI after successful primary PCI with a concurrent
      CTO. Patients were randomised to either CTO-PCI or CTO-No PCI. The primary end
      point of the current study was occurrence of major adverse cardiac events (MACE):
      cardiac death, coronary artery bypass grafting and MI. Other end points were 1
      year left ventricular function (LVF); LV-ejection fraction and LV end-diastolic
      volume and angina status. RESULTS: The median long-term follow-up was 3.9 (2.1
      5.0) years. MACE was not significantly different between both arms (13.5% vs
      12.3%, HR 1.03, 95% CI 0.54 to 1.98; P=0.93). Cardiac death was more frequent in
      the CTO-PCI arm (6.0% vs 1.0%, P=0.02) with no difference in all-cause mortality
      (12.9% vs 6.2%, HR 2.07, 95% CI 0.84 to 5.14; P=0.11). One-year LVF did not
      differ between both arms. However, there were more patients with freedom of
      angina in the CTO-PCI arm at 1 year (94% vs 87%, P=0.03). CONCLUSIONS: In this
      randomised trial involving patients with STEMI with a concurrent CTO, CTO-PCI was
      not associated with a reduction in long-term MACE compared to CTO-No PCI. One
      year LVF was comparable between both treatment arms. The finding that there were
      more patients with freedom of angina after CTO-PCI at 1-year follow-up needs
      further investigation. CLINICAL TRIAL REGISTRATION: EXPLORE trial number NTR1108
      www.trialregister.nl.

PMID- 29463613
TI  - Selection bias, interventions and outcomes for survivors of cardiac arrest.
AB  - OBJECTIVE: Cardiac catheterisation and implantable cardioverter defibrillator
      (ICD) insertion are increasingly common following cardiac arrest survival.
      However, much of the evidence for the benefit is observational, leaving open the
      possibility that biased patient selection confounds the association between these
      invasive procedures and improved outcome. We evaluated the likelihood of
      selection bias in the association between cardiac catheterisation or ICD
      placement and outcome by measuring long-term outcomes overall and in a cause
      specific approach that separated cardiac mortality from non-cardiac mortality.
      METHODS: We performed a multivariable survival analysis of a clinical cohort
      between 2005 and 2013, with follow-up through 2015. We included patients who had
      out-of-hospital or inhospital cardiac arrest that survived to discharge, and
      evaluated the association between cardiac catheterisation or ICD insertion and
      all-cause, cardiovascular and non-cardiovascular mortality. RESULTS: Among 678
      patients who survived cardiac arrest, we observed lower all-cause mortality among
      patients who underwent cardiac catheterisation (adjusted HR (aHR) 0.40; P<0.01)
      or ICD insertion (aHR 0.55; P<0.01). However, cause-specific analysis showed that
      the benefits of cardiac catheterisation and ICD insertion resulted from reduced
      non-cardiac causes of death (cardiac catheterisation: aHR 0.24, P<0.01; ICD: aHR
      0.58, P<0.01), while reduced cardiac cause of death was not associated with
      cardiac catheterisation (cardiac catheterisation: aHR 0.75, P=0.33). CONCLUSIONS:
      There is evidence of selection bias in the secondary prevention survival benefit
      attributable to cardiac catheterisation for patients who survive cardiac arrest.
      Observational studies that consider its effects on all-cause mortality likely
      overestimate the potential benefit of this procedure.

PMID- 29463614
TI  - Consensus guidelines on the optimal management in interventional EUS procedures:
      results from the Asian EUS group RAND/UCLA expert panel.
AB  - OBJECTIVES: Interventional endoscopic ultrasonography (EUS) procedures are
      gaining popularity and the most commonly performed procedures include EUS-guided
      drainage of pancreatic pseudocyst, EUS-guided biliary drainage, EUS-guided
      pancreatic duct drainage and EUS-guided celiac plexus ablation. The aim of this
      paper is to formulate a set of practice guidelines addressing various aspects of
      the above procedures. METHODS: Formulation of the guidelines was based on the
      best scientific evidence available. The RAND/UCLA appropriateness methodology
      (RAM) was used. Panellists recruited comprised experts in surgery, interventional
      EUS, interventional radiology and oncology from 11 countries. Between June 2014
      and October 2016, the panellists met in meetings to discuss and vote on the
      clinical scenarios for each of the interventional EUS procedures in question.
      RESULTS: A total of 15 statements on EUS-guided drainage of pancreatic
      pseudocyst, 15 statements on EUS-guided biliary drainage, 12 statements on EUS
      guided pancreatic duct drainage and 14 statements on EUS-guided celiac plexus
      ablation were formulated. The statements addressed the indications for the
      procedures, technical aspects, pre- and post-procedural management, management of
      complications, and competency and training in the procedures. All statements
      except one were found to be appropriate. Randomised studies to address clinical
      questions in a number of aspects of the procedures are urgently required.
      CONCLUSIONS: The current guidelines on interventional EUS procedures are the
      first published by an endoscopic society. These guidelines provide an in-depth
      review of the current evidence and standardise the management of the procedures.

PMID- 29463615
TI  - Thioester-Containing Proteins 2 and 4 Affect the Metabolic Activity and
      Inflammation Response in Drosophila.
AB  - Drosophila melanogaster is an outstanding model for studying host antipathogen
      defense. Although substantial progress has been made in understanding how
      metabolism and immunity are interrelated in flies, little information has been
      obtained on the molecular players that regulate metabolism and inflammation in
      Drosophila during pathogenic infection. Recently, we reported that the
      inactivation of thioester-containing protein 2 (Tep2) and Tep4 promotes survival
      and decreases the bacterial burden in flies upon infection with the virulent
      pathogens Photorhabdus luminescens and Photorhabdus asymbiotica Here, we
      investigated physiological and pathological defects in tep mutant flies in
      response to Photorhabdus challenge. We find that tep2 and tep4 loss-of-function
      mutant flies contain increased levels of carbohydrates and triglycerides in the
      presence or absence of Photorhabdus infection. We also report that Photorhabdus
      infection leads to higher levels of nitric oxide and reduced transcript levels of
      the apical caspase-encoding gene Dronc in tep2 and tep4 mutants. We show that
      Tep2 and Tep4 are upregulated mainly in the fat body rather than the gut in
      Photorhabdus-infected wild-type flies and that tep mutants contain decreased
      numbers of Photorhabdus bacteria in both tissue types. We propose that the
      inactivation of Tep2 or Tep4 in adult Drosophila flies results in lower levels of
      inflammation and increased energy reserves in response to Photorhabdus, which
      could confer a survival-protective effect during the initial hours of infection.

PMID- 29463616
TI  - Absence of Receptor Guanylyl Cyclase C Enhances Ileal Damage and Reduces Cytokine
      and Antimicrobial Peptide Production during Oral Salmonella enterica Serovar
      Typhimurium Infection.
AB  - Nontyphoidal Salmonella disease contributes toward significant morbidity and
      mortality across the world. Host factors, including gamma interferon, tumor
      necrosis factor alpha, and gut microbiota, significantly influence the outcome of
      Salmonella pathogenesis. However, the entire repertoire of host protective
      mechanisms contributing to Salmonella pathogenicity is not completely
      appreciated. Here, we investigated the roles of receptor guanylyl cyclase C (GC
      C), which is predominantly expressed in the intestine and regulates intestinal
      cell proliferation and fluid-ion homeostasis. Mice deficient in GC-C (Gucy2c-/-)
      displayed accelerated mortality compared with that for wild-type mice following
      infection via the oral route, even though both groups possessed comparable
      systemic Salmonella infection burdens. Survival following intraperitoneal
      infection remained similar in both groups, indicating that GC-C offered
      protection via a gut-mediated response. The serum cortisol level was higher in
      Gucy2c-/- mice than wild-type (Gucy2c+/+) mice, and an increase in infection
      induced thymic atrophy with a loss of immature CD4+ CD8+ double-positive
      thymocytes was observed. Accelerated and enhanced damage in the ileum, including
      submucosal edema, epithelial cell damage, focal tufting, and distortion of the
      villus architecture, was seen in Gucy2c-/- mice concomitantly with a larger
      number of ileal tissue-associated bacteria. Transcription of key mediators of
      Salmonella-induced inflammation (interleukin-22/Reg3beta) was altered in Gucy2c-/
      mice in comparison to that in Gucy2c+/+ mice. A reduction in fecal lactobacilli,
      which are protective against Salmonella infection, was observed in Gucy2c-/-
      mice. Gucy2c-/- mice cohoused with wild-type mice continued to show reduced
      amounts of lactobacilli and increased susceptibility to infection. Our study,
      therefore, suggests that the receptor GC-C confers a survival advantage during
      gut-mediated Salmonella enterica serovar Typhimurium pathogenesis, presumably by
      regulating Salmonella effector mechanisms and maintaining a beneficial
      microbiome.

PMID- 29463617
TI  - The Chlamydia trachomatis Plasmid and CT135 Virulence Factors Are Not Essential
      for Genital Tract Infection or Pathology in Female Pig-Tailed Macaques.
AB  - The Chlamydia trachomatis plasmid and inclusion membrane protein CT135 are
      virulence factors in the pathogenesis of murine female genital tract infection.
      To determine if these virulence factors play a similar role in female nonhuman
      primates, we infected pig-tailed macaques with the same C. trachomatis strains
      shown to be important in the murine model. Wild-type C. trachomatis and its
      isogenic mutant strain deficient in both plasmid and CT135 were used to infect
      macaques. Macaques were given primary and repeated cervicovaginal challenges with
      the wild-type and mutant strains. The infection rate, infection duration, and
      antibody response were similar among macaques infected with both strains.
      Unexpectedly, colposcopy, laparoscopy, and histologic analysis revealed no
      substantial genital tract pathology following either primary or repeated
      cervicovaginal challenges. Cytokine analysis of cervicovaginal secretions from
      both challenged groups revealed low concentrations of interleukin 1beta (IL
      1beta) and elevated levels of the interleukin 1 receptor agonist (IL-1RA). We
      propose that an imbalance of IL-1beta and IL-1RA in macaques is the reason for
      the mild inflammatory responses observed in infected urogenital tissues. Thus,
      understanding the pathobiology of chlamydial infection requires a better
      understanding of host epigenetic and chlamydial genetic factors. Our findings
      also have implications for understanding the high frequency of asymptomatic
      infections in humans.

PMID- 29463618
TI  - Evaluation of the Role of stat3 in Antibody and TH17-Mediated Responses to
      Pneumococcal Immunization and Infection by Use of a Mouse Model of Autosomal
      Dominant Hyper-IgE Syndrome.
AB  - Loss-of-function mutations in the signal transducer and activator of
      transcription 3 gene (stat3) result in autosomal dominant hyper-IgE syndrome (AD
      HIES), a condition in which patients have recurrent debilitating infections,
      including frequent pneumococcal and staphylococcal pneumonias. stat3 mutations
      cause defective adaptive TH17 cellular responses, an immune mechanism believed to
      be critical for clearance of pneumococcal colonization and diminished antibody
      responses. Here we wished to evaluate the role of stat3 in the clearance of
      pneumococcal carriage and immunity using mice with a stat3 mutation
      recapitulating AD-HIES. We show here that naive AD-HIES mice have prolonged nasal
      carriage of pneumococcus compared to WT mice. Mutant and wild-type mice were then
      immunized with a pneumococcal whole-cell vaccine (WCV) that provides TH17
      mediated protection against pneumococcal colonization and antibody-mediated
      protection against pneumonia and sepsis. WCV-immunized AD-HIES mice made
      significantly less pneumococcus-specific interleukin-17A (IL-17A) and antibody
      than WT mice. The WCV-elicited protection against colonization was abrogated in
      AD-HIES mice, but immunization with WCV still protected AD-HIES mice against
      aspiration pneumonia/sepsis. Taken together, our results suggest that impaired
      clearance of nasopharyngeal carriage due to poor adaptive IL-17A responses may
      contribute to the increased rates of pneumococcal respiratory infection in AD
      HIES patients.

PMID- 29463619
TI  - A comparison of direct aspiration versus stent retriever as a first approach
      ('COMPASS'): protocol.
AB  - BACKGROUND AND OBJECTIVE: Acute ischemic stroke is a potentially devastating
      condition and leading cause of morbidity and mortality, affecting an estimated
      800 000 people per year in the USA. The natural history of untreated or
      unrevascularized large vessel occlusions in acute stroke patients results in
      mortality rates approaching 30%, with only 25% achieving good neurologic outcomes
      at 90 days. Recently, data have demonstrated that early endovascular
      recanalization of large vessel occlusions results in better outcomes than medical
      therapy alone. However, the majority of patients in these studies were treated
      with a stent retriever based approach. The purpose of COMPASS is to evaluate
      whether patients treated with a direct aspiration first pass (ADAPT) approach
      have non-inferior functional outcomes to those treated with a stent retriever as
      the firstline (SRFL) approach. MATERIALS AND METHODS: All patients who meet the
      inclusion and exclusion criteria and consent to participate will be enrolled at
      participating centers. Treatment will be randomly assigned by a central web based
      system in a 1:1 manner to treatment with either ADAPT or SRFL thrombectomy.
      Statistical methodology is prespecified with details available in the statistical
      analysis plan. RESULTS: The trial recently completed enrollment, and data
      collection/verification is ongoing. The final results will be made available on
      completion of enrollment and follow-up. CONCLUSIONS: This paper details the
      design of the COMPASS trial, a randomized, blinded adjudicator, concurrent,
      controlled trial of patients treated with either ADAPT or SRFL approaches in
      order to evaluate whether ADAPT results in non-inferior functional outcome. TRIAL
      REGISTRATION NUMBER: NCT02466893, Results.

PMID- 29463620
TI  - Infectious intracranial aneurysms: a systematic review of epidemiology,
      management, and outcomes.
AB  - Infectious intracranial aneurysms (IIAs) are a rare cerebrovascular complication
      of systemic infections induced by microbial infiltration and degradation of the
      arterial vessel wall. Studies on the epidemiology and management of IIAs are
      limited to case reports and retrospective single-center studies, and report a
      large variability in epidemiological features, management, and outcomes due to
      the limited sample size. We conducted a systematic review of all published papers
      on IIAs in the English literature using MEDLINE and SCOPUS database from January
      1950 to June 2017. A total of 288 publications describing 1191 patients with IIA
      (1398 aneurysms) were included and reviewed for epidemiological features, disease
      features, treatment and outcome. All patients were merged into a single cohort
      and summary data are presented. The majority of reported IIAs are distally
      located, relatively small (<5 mm), involve the anterior circulation, are
      associated with a relatively high rate of rupture, and demonstrate a propensity
      to multiplicity of aneurysms. Sensitive diagnosis of IIAs requires digital
      subtraction angiography and not CT angiography or MR angiography. Treatment of
      ruptured, symptomatic, or enlarging IIAs has evolved over the last 50 years.
      Endovascular therapy is associated with a high success rate and low morbidity
      compared with microsurgical and medical management. A treatment algorithm for the
      management of patients with IIA in various contexts is proposed and the need for
      prospective multicenter studies is emphasized.

PMID- 29463621
TI  - Ventilatory support or respiratory muscle training as adjuncts to exercise in
      obese CPAP-treated patients with obstructive sleep apnoea: a randomised
      controlled trial.
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) and obesity are interdependent chronic
      diseases sharing reduced exercise tolerance and high cardiovascular risk.
      INTERVENTION: A 3-month intervention with innovative training modalities would
      further improve functional capacity and cardiovascular health than usual cycle
      exercise training in already continuous positive airway pressure (CPAP)-treated
      obese patients with OSA. METHODS: Fifty three patients (35<body mass index (BMI)
      <45 kg/m2) were randomly allocated to exercise training on a cycle ergometer,
      either alone (ERGO) or with respiratory muscle training (ERGO+RMT) or non
      invasive ventilation (ERGO+NIV). Changes in 6 min walking distance (primary
      outcome), aerobic capacity (VO2peak), cardiovascular parameters, body composition
      and sleep quality were evaluated. MEASUREMENTS AND MAIN RESULTS: All training
      modalities increased 6 min walking distance without differences between groups
      (P=0.97). ERGO+NIV and ERGO+RMT led to significantly higher improvement in
      VO2peak compared with ERGO (3.1 (95% CI 1.6 to 4.6) vs 2.3 (0.8 to 3.7) vs 0.5(
      1.0 to 1.9) mL/min/kg, respectively, P=0.04) and ERGO+NIV significantly reduced
      self-measured blood pressure compared with ERGO+RMT and ERGO (systolic: -9.5 (95%
      CI -14.1 to -4.9) vs -13 (-5.8 to 3.1) vs -0.7 (-5.1 to 3.8) mm Hg, respectively,
      P=0.01). Waist and neck circumferences were reduced after ERGO+NIV compared with
      ERGO+RMT and ERGO (P=0.01). CONCLUSIONS: Combining RMT or NIV with cycling
      exercise training failed to provide further improvement in functional capacity as
      compared with cycling exercise training alone. However, the combination of NIV
      and exercise training demonstrated superiority for improving cardiometabolic risk
      factors in obese CPAP-treated patients with OAS. TRIAL REGISTRATION NUMBER:
      Results, NCT01155271.

PMID- 29463622
TI  - Implementation science takes baby steps in infants with bronchiolitis.

PMID- 29463623
TI  - Regulatory role for host environment in post-ischaemic stem cell differentiation.

PMID- 29463625
TI  - Growth Differentiation Factor 11 Promotes Abnormal Proliferation and Angiogenesis
      of Pulmonary Artery Endothelial Cells.
AB  - Disordered proliferation and angiogenesis of pulmonary artery endothelial cells
      is an important stage in the development of pulmonary arterial hypertension.
      Recent studies revealed that GDF11 (growth differentiation factor 11) induces
      endothelial cells proliferation and migration; however, whether GDF11 is directly
      involved in the pathogenesis of pulmonary arterial hypertension remains unknown.
      Here, we found that GDF11 was significantly upregulated and activated in 2
      experimental pulmonary arterial hypertension models and cultured pulmonary artery
      endothelial cells. Genetic ablation of gdf11 in endothelial cells rescued
      pulmonary arterial hypertension features, as demonstrated by right ventricle
      hypertrophy, right ventricular systolic pressure, hemodynamics, cardiac function,
      and vascular remodeling. Moreover, we found that hypoxia significantly increased
      cell cycle progression, proliferation, migration, adhesion, and tube formation,
      which were significantly inhibited by GDF11 small interfering RNA. These events
      could be reproduced using cultured pulmonary artery endothelial cells and were
      dependent on Smad signaling. Moreover, hypoxia-induced GDF11 expression was
      regulated by the transcription factor zinc finger protein 740, which assisted RNA
      polymerase in recognizing and binding to the GDF11 promoter sequence located at a
      site (-753/-744; CCCCCCCCAC) upstream of the gene. This study identified a novel
      growth and differentiation factor signaling pathway involved in the zinc finger
      protein 740/GDF11/transforming growth factor-beta receptor I/Smad signaling axis
      and involved in pulmonary artery endothelial cells proliferation and
      angiogenesis. These results provide critical insights for the development of
      novel therapeutic strategies for pulmonary arterial hypertension involving
      components of the GDF11 signaling system.

PMID- 29463624
TI  - Smooth Muscle Cell-Mineralocorticoid Receptor as a Mediator of Cardiovascular
      Stiffness With Aging.
AB  - Stiffening of the vasculature with aging is a strong predictor of adverse
      cardiovascular events, independent of all other risk factors including blood
      pressure, yet no therapies target this process. MRs (mineralocorticoid receptors)
      in smooth muscle cells (SMCs) have been implicated in the regulation of vascular
      fibrosis but have not been explored in vascular aging. Comparing SMC-MR-deleted
      male mice to MR-intact littermates at 3, 12, and 18 months of age, we
      demonstrated that aging-associated vascular stiffening and fibrosis are mitigated
      by MR deletion in SMCs. Progression of cardiac stiffness and fibrosis and the
      decline in exercise capacity with aging were also mitigated by MR deletion in
      SMC. Vascular gene expression profiling analysis revealed that MR deletion in SMC
      is associated with recruitment of a distinct antifibrotic vascular gene
      expression program with aging. Moreover, long-term pharmacological inhibition of
      MR in aged mice prevented the progression of vascular fibrosis and stiffness and
      induced a similar antifibrotic vascular gene program. Finally, in a small trial
      in elderly male humans, short-term MR antagonism produced an antifibrotic
      signature of circulating biomarkers similar to that observed in the vasculature
      of SMC-MR-deleted mice. These findings suggest that SMC-MR contributes to
      vascular stiffening with aging and is a potential therapeutic target to prevent
      the progression of aging-associated vascular fibrosis and stiffness.

PMID- 29463626
TI  - Maternal and Paternal Height and the Risk of Preeclampsia.
AB  - The etiology of preeclampsia is unknown. Tall women have been found to have lower
      incidence of preeclampsia. This points to a possible biological causal effect but
      may be because of socioeconomic confounding. We used paternal height as an
      unexposed control to examine confounding. The MoBa (Norwegian Mother and Child
      Cohort Study) was used to extract data on parental heights, maternal prepregnancy
      weight, other background factors, and pregnancy outcomes for 99 968 singleton
      births. Multiple logistic regression was used to estimate odds ratios for
      preeclampsia according to parental height. The adjusted odds ratio for
      preeclampsia was 0.74 (95% CI, 0.66-0.82) for women >172 cm as compared with
      women <164 cm. The adjusted odds ratio for preeclampsia for men >186 cm was 1.03
      (95% CI, 0.93-1.15) compared with men <178 cm. The association between maternal
      height and preeclampsia is unlikely to be because of confounding by familial,
      socioeconomic factors or by fetal genes related to height. The observed
      association between maternal height and preeclampsia merits further
      investigation.

PMID- 29463628
TI  - Looking back and forward: emergency medicine in its 50th year.

PMID- 29463627
TI  - Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant
      Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal
      Treatment).
AB  - : The aim of this study is to compare spironolactone versus clonidine as the
      fourth drug in patients with resistant hypertension in a multicenter, randomized
      trial. Medical therapy adherence was checked by pill counting. Patients with
      resistant hypertension (no office and ambulatory blood pressure [BP] monitoring
      control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were
      randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD)
      or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office
      (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end
      points included BP control from each method and absolute BP reduction. From 1597
      patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension
      criteria. Compared with the spironolactone group (n=95), the clonidine group
      (n=92) presented similar rates of achieving the primary end point (20.5% versus
      20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end
      point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP
      monitoring (44% versus 46.2%) control for spironolactone and clonidine,
      respectively. However, spironolactone promoted greater decrease in 24-h systolic
      and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol
      analysis (limited to patients with >=80% adherence to spironolactone/clonidine
      treatment) showed similar results regarding the primary end point. In conclusion,
      clonidine was not superior to spironolactone in true resistant hypertensive
      patients, but the overall BP control was low (~21%). Considering easier posology
      and greater decrease in secondary end points, spironolactone is preferable for
      the fourth-drug therapy. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01643434.

PMID- 29463629
TI  - Being a pioneer in emergency medicine.

PMID- 29463630
TI  - Emergency nursing: recognising and celebrating the contribution.

PMID- 29463631
TI  - Brief history of Pre-Hospital Emergency Medicine.

PMID- 29463632
TI  - An injured man with acute altered mental status.
AB  - CLINICAL INTRODUCTION: A 58-year-old man sustained injuries due to accidental
      fall from a height of 5 m onto a solid floor while operating a crane. He was
      fully conscious without external evidence of head injury when presented to the
      ED. The patient had multiple fractures involving the fourth, fifth and seventh of
      the left ribs, left iliac wing and superior ramus of the pelvis, comminuted
      fracture of the left femur shaft, and an open fracture of the mandible. Two hours
      after ED presentation, the patient developed acute confusion and lethargy, which
      rapidly progressed to coma and respiratory distress, and was subsequently
      intubated with mechanical ventilation support. Emergent CT scan of the head is
      shown (figure 1).emermed;35/3/148/F1F1F1Figure 1CT scan of the head without
      contrast. QUESTION: What is the most likely diagnosis?A. Cerebral haemorrhageB.
      Brain metastasisC. Cerebral fat embolismD. Diffuse axonal injury.

PMID- 29463633
TI  - Emergency medicine research: how far have we come and where are we heading?

PMID- 29463634
TI  - Emergency Medicine: great papers from the Summer of Love to 2017.

PMID- 29463635
TI  - How can emergency physicians harness the power of new technologies in clinical
      practice and education?
AB  - As the Royal College of Emergency Medicine looks back on 50 years of progress
      towards the future it is clear that new and emerging technologies have the
      potential to substantially change the practice of emergency medicine. Education,
      diagnostics, therapeutics are all likely to change as algorithms, personalised
      medicine and insights into complexity become more readily available to the
      emergency clinician. This paper outlines areas of our practice that are already
      changing and speculates on how we might need to prepare our workforce for a
      technologically enhanced future.

PMID- 29463636
TI  - How do we educate the next generation of emergency physicians: RCEM 50.

PMID- 29463637
TI  - A diagnostic red herring.
AB  - : CLINICAL INTRODUCTION: A 29-year-old keen parachutist presented to the
      emergency services in Cyprus complaining of sudden-onset facial flushing,
      dizziness and a widespread rash. The episode began on a hot day, 1 hour after she
      had eaten a breakfast of tinned tuna, and while she was ascending in an aircraft
      to parachute from 10 000 ft. She completed her jump uneventfully. She had no
      significant medical history (figure 1).emermed;35/3/184/F1F1F1Figure 1Patient's
      legs on presentation; this rash was generalised. QUESTION: Based on the history
      and rash, which ONE of the following is the most likely diagnosis?Fish
      allergyHeat-related eruptionScombrotoxin poisoningStress-induced urticaria.

PMID- 29463639
TI  - Bet 1: A slower rate of initial N-acetylcysteine infusion in the treatment of
      acute paracetamol overdose to reduce adverse reactions.

PMID- 29463640
TI  - Bet 2: Estimating CD4+ counts from the absolute lymphocyte count in the ED.

PMID- 29463641
TI  - Ultrasound Elicits Behavioral Responses through Mechanical Effects on Neurons and
      Ion Channels in a Simple Nervous System.
AB  - Focused ultrasound has been shown to stimulate excitable cells, but the
      biophysical mechanisms behind this phenomenon remain poorly understood. To
      provide additional insight, we devised a behavioral-genetic assay applied to the
      well-characterized nervous system of Caenorhabditis elegans nematodes. We found
      that pulsed ultrasound elicits robust reversal behavior in wild-type animals in a
      pressure-, duration-, and pulse protocol-dependent manner. Responses were
      preserved in mutants unable to sense thermal fluctuations and absent in mutants
      lacking neurons required for mechanosensation. Additionally, we found that the
      worm's response to ultrasound pulses rests on the expression of MEC-4, a
      DEG/ENaC/ASIC ion channel required for touch sensation. Consistent with prior
      studies of MEC-4-dependent currents in vivo, the worm's response was optimal for
      pulses repeated 300-1000 times per second. Based on these findings, we conclude
      that mechanical, rather than thermal, stimulation accounts for behavioral
      responses. Further, we propose that acoustic radiation force governs the response
      to ultrasound in a manner that depends on the touch receptor neurons and MEC-4
      dependent ion channels. Our findings illuminate a complete pathway of ultrasound
      action, from the forces generated by propagating ultrasound to an activation of a
      specific ion channel. The findings further highlight the importance of optimizing
      ultrasound pulsing protocols when stimulating neurons via ion channels with
      mechanosensitive properties.SIGNIFICANCE STATEMENT How ultrasound influences
      neurons and other excitable cells has remained a mystery for decades. Although it
      is widely understood that ultrasound can heat tissues and induce mechanical
      strain, whether or not neuronal activation depends on heat, mechanical force, or
      both physical factors is not known. We harnessed Caenorhabditis elegans nematodes
      and their extraordinary sensitivity to thermal and mechanical stimuli to address
      this question. Whereas thermosensory mutants respond to ultrasound similar to
      wild-type animals, mechanosensory mutants were insensitive to ultrasound
      stimulation. Additionally, stimulus parameters that accentuate mechanical effects
      were more effective than those producing more heat. These findings highlight a
      mechanical nature of the effect of ultrasound on neurons and suggest specific
      ways to optimize stimulation protocols in specific tissues.

PMID- 29463642
TI  - The Effect of Locomotion on Early Visual Contrast Processing in Humans.
AB  - Most of our knowledge about vision comes from experiments in which stimuli are
      presented to immobile human subjects or animals. In the case of human subjects,
      movement during psychophysical, electrophysiological, or neuroimaging experiments
      is considered to be a source of noise to be eliminated. Animals used in visual
      neuroscience experiments are typically restrained and, in many cases,
      anesthetized. In reality, however, vision is often used to guide the motion of
      awake, ambulating organisms. Recent work in mice has shown that locomotion
      elevates visual neuronal response amplitudes (Niell and Stryker, 2010; Erisken et
      al., 2014; Fu et al., 2014; Lee et al., 2014; Mineault et al., 2016) and reduces
      long-range gain control (Ayaz et al., 2013). Here, we used both psychophysics and
      steady-state electrophysiology to investigate whether similar effects of
      locomotion on early visual processing can be measured in humans. Our
      psychophysical results show that brisk walking has little effect on subjects'
      ability to detect briefly presented contrast changes and that co-oriented
      flankers are, if anything, more effective masks when subjects are walking. Our
      electrophysiological data were consistent with the psychophysics indicating no
      increase in stimulus-driven neuronal responses while walking and no reduction in
      surround suppression. In summary, we have found evidence that early contrast
      processing is altered by locomotion in humans but in a manner that differs from
      that reported in mice. The effects of locomotion on very low-level visual
      processing may differ on a species-by-species basis and may reflect important
      differences in the levels of arousal associated with locomotion.SIGNIFICANCE
      STATEMENT Mice are the current model of choice for studying low-level visual
      processing. Recent studies have shown that mouse visual cortex is modulated by
      behavioral state: primary visual cortex neurons in locomoting mice tend to be
      more sensitive and less influenced by long-range gain control. Here, we tested
      these effects in humans by measuring psychophysical detection thresholds and
      electroencephalography (EEG) responses while subjects walked on a treadmill. We
      found no evidence of increased contrast sensitivity or reduced surround
      suppression in walking humans. Our data show that fundamental measurements of
      early visual processing differ between humans and mice and this has important
      implications for recent work on the links among arousal, behavior, and vision in
      these two species.

PMID- 29463643
TI  - Hyperactivity of Anterior Cingulate Cortex Areas 24a/24b Drives Chronic Pain
      Induced Anxiodepressive-like Consequences.
AB  - Pain associates both sensory and emotional aversive components, and often leads
      to anxiety and depression when it becomes chronic. Here, we characterized, in a
      mouse model, the long-term development of these sensory and aversive components
      as well as anxiodepressive-like consequences of neuropathic pain and determined
      their electrophysiological impact on the anterior cingulate cortex (ACC, cortical
      areas 24a/24b). We show that these symptoms of neuropathic pain evolve and
      recover in different time courses following nerve injury in male mice. In vivo
      electrophysiological recordings evidence an increased firing rate and bursting
      activity within the ACC when anxiodepressive-like consequences developed, and
      this hyperactivity persists beyond the period of mechanical hypersensitivity.
      Whole-cell patch-clamp recordings also support ACC hyperactivity, as shown by
      increased excitatory postsynaptic transmission and contribution of NMDA
      receptors. Optogenetic inhibition of the ACC hyperactivity was sufficient to
      alleviate the aversive and anxiodepressive-like consequences of neuropathic pain,
      indicating that these consequences are underpinned by ACC
      hyperactivity.SIGNIFICANCE STATEMENT Chronic pain is frequently comorbid with
      mood disorders, such as anxiety and depression. It has been shown that it is
      possible to model this comorbidity in animal models by taking into consideration
      the time factor. In this study, we aimed at determining the dynamic of different
      components and consequences of chronic pain, and correlated them with
      electrophysiological alterations. By combining electrophysiological, optogenetic,
      and behavioral analyses in a mouse model of neuropathic pain, we show that the
      mechanical hypersensitivity, ongoing pain, anxiodepressive consequences, and
      their recoveries do not necessarily exhibit temporal synchrony during chronic
      pain processing, and that the hyperactivity of the anterior cingulate cortex is
      essential for driving the emotional impact of neuropathic pain.

PMID- 29463644
TI  - The inositol-requiring enzyme 1 (IRE1alpha) RNAse inhibitor, 4u8C, is also a
      potent cellular antioxidant.
AB  - Inositol-requiring enzyme 1 alpha (IRE1alpha) is an endoplasmic reticulum (ER)
      transmembrane endonuclease that is activated in response to ER stress as part of
      the unfolded protein response (UPR). Chronic activation of the UPR has been
      implicated in the pathogenesis of many common diseases including diabetes,
      cancer, and neurological pathologies such as Huntington's and Alzheimer's
      disease. 7-Hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde (4u8C) is widely
      used as a specific inhibitor of IRE1alpha ribonuclease activity (IC50 of 6.89 uM
      in cultured cells). However, in this paper, we demonstrate that 4u8C acts as a
      potent reactive oxygen species (ROS) scavenger, both in a cell-free assay and in
      cultured cells, at concentrations lower than that widely used to inhibit
      IRE1alpha activity. In vitro we show that, 4u8C effectively decreases
      xanthine/xanthine oxidase catalysed superoxide production with an IC50 of 0.2 uM
      whereas in cultured endothelial and clonal pancreatic beta-cells, 4u8C inhibits
      angiotensin II-induced ROS production with IC50 values of 1.92 and 0.29 uM,
      respectively. In light of this discovery, conclusions reached using 4u8C as an
      inhibitor of IRE1alpha should be carefully evaluated. However, this unexpected
      off-target effect of 4u8C may prove therapeutically advantageous for the
      treatment of pathologies that are thought to be caused by, or exacerbated by,
      both oxidative and ER stress such as endothelial dysfunction and/or diabetes.

PMID- 29463645
TI  - Molecular Architecture of the Essential Yeast Histone Acetyltransferase Complex
      NuA4 Redefines Its Multimodularity.
AB  - Conserved from yeast to humans, the NuA4 histone acetyltransferase is a large
      multisubunit complex essential for cell viability through the regulation of gene
      expression, genome maintenance, metabolism, and cell fate during development and
      stress. How the different NuA4 subunits work in concert with one another to
      perform these diverse functions remains unclear, and addressing this central
      question requires a comprehensive understanding of NuA4's molecular architecture
      and subunit organization. We have determined the structure of fully assembled
      native yeast NuA4 by single-particle electron microscopy. Our data revealed that
      NuA4 adopts a trilobal overall architecture, with each of the three lobes
      constituted by one or two functional modules. By performing cross-linking coupled
      to mass spectrometry analysis and in vitro protein interaction studies, we
      further mapped novel intermolecular interfaces within NuA4. Finally, we combined
      these new data with other known structural information of NuA4 subunits and
      subassemblies to construct a multiscale model to illustrate how the different
      NuA4 subunits and modules are spatially arranged. This model shows that the
      multiple chromatin reader domains are clustered together around the catalytic
      core, suggesting that NuA4's multimodular architecture enables it to engage in
      multivalent interactions with its nucleosome substrate.

PMID- 29463646
TI  - Mutant Isocitrate Dehydrogenase 1 Disrupts PKM2-beta-Catenin-BRG1 Transcriptional
      Network-Driven CD47 Expression.
AB  - A gain-of-function mutation in isocitrate dehydrogenase 1 (IDH1) affects immune
      surveillance in gliomas. As elevated CD47 levels are associated with immune
      evasion in cancers, its status in gliomas harboring mutant IDH1 (IDH1-MT cells)
      was investigated. Decreased CD47 expression in IDH1-R132H-overexpressing cells
      was accompanied by diminished nuclear beta-catenin, pyruvate kinase isoform M2
      (PKM2), and TCF4 levels compared to those in cells harboring wild-type IDH1 (IDH1
      WT cells). The inhibition of beta-catenin in IDH1-WT cells abrogated CD47
      expression, beta-catenin-TCF4 interaction, and the transactivational activity of
      beta-catenin/TCF4. The reverse effect was observed in IDH1-MT cells upon the
      pharmacological elevation of nuclear beta-catenin levels. Genetic and
      pharmacological manipulation of nuclear PKM2 levels in IDH1-WT and IDH1-MT cells
      suggested that PKM2 is a positive regulator of the beta-catenin-TCF4 interaction.
      The Cancer Genome Atlas (TCGA) data sets indicated diminished CD47, PKM2, and
      beta-catenin levels in IDH1-MT gliomas compared to IDH1-WT gliomas. Also,
      elevated BRG1 levels with mutations in the ATP-dependent chromatin-remodeling
      site were observed in IDH1-MT glioma. The ectopic expression of ATPase-deficient
      BRG1 diminished CD47 expression as well as TCF4 occupancy on its promoter.
      Sequential chromatin immunoprecipitation (ChIP-re-ChIP) revealed the recruitment
      of the PKM2-beta-catenin-BRG1-TCF4 complex to the TCF4 site on the CD47 promoter.
      This occupancy translated into CD47 transcription, as a diminished recruitment of
      this complex was observed in glioma cells bearing IDH1-R132H. In addition to its
      involvement in CD47 transcriptional regulation, PKM2-beta-catenin-BRG1 cross talk
      affected the phagocytosis of IDH1-MT cells by microglia.

PMID- 29463647
TI  - beta1-Integrin Impacts Rad51 Stability and DNA Double-Strand Break Repair by
      Homologous Recombination.
AB  - The molecular mechanisms underlying resistance to radiotherapy in breast cancer
      cells remain elusive. Previously, we reported that elevated beta1-integrin is
      associated with enhanced breast cancer cell survival postirradiation, but how
      beta1-integrin conferred radioresistance was unclear. Ionizing radiation (IR)
      induced cell killing correlates with the efficiency of DNA double-strand break
      (DSB) repair, and we found that nonmalignant breast epithelial (S1) cells with
      low beta1-integrin expression have a higher frequency of S-phase-specific IR
      induced chromosomal aberrations than the derivative malignant breast (T4-2) cells
      with high beta1-integrin expression. In addition, there was an increased
      frequency of IR-induced homologous recombination (HR) repairosome focus formation
      in T4-2 cells compared with that of S1 cells. Cellular levels of Rad51 in T4-2
      cells, a critical factor in HR-mediated DSB repair, were significantly higher.
      Blocking or depleting beta1-integrin activity in T4-2 cells reduced Rad51 levels,
      while ectopic expression of beta1-integrin in S1 cells correspondingly increased
      Rad51 levels, suggesting that Rad51 is regulated by beta1-integrin. The low level
      of Rad51 protein in S1 cells was found to be due to rapid degradation by the
      ubiquitin proteasome pathway (UPP). Furthermore, the E3 ubiquitin ligase RING1
      was highly upregulated in S1 cells compared to T4-2 cells. Ectopic beta1-integrin
      expression in S1 cells reduced RING1 levels and increased Rad51 accumulation. In
      contrast, beta1-integrin depletion in T4-2 cells significantly increased RING1
      protein levels and potentiated Rad51 ubiquitination. These data suggest for the
      first time that elevated levels of the extracellular matrix receptor beta1
      integrin can increase tumor cell radioresistance by decreasing Rad51 degradation
      through a RING1-mediated proteasomal pathway.

PMID- 29463648
TI  - Id2 determines intestinal identity through repression of the foregut
      transcription factor, Irx5.
AB  - The cellular components and function of the gastrointestinal epithelium exhibit
      distinct characteristics depending on the region, e.g., stomach or intestine. How
      these region-specific epithelial characteristics are generated during development
      remains poorly understood. Here, we report on the involvement of the helix-loop
      helix inhibitor Id2 in establishing the specific characteristics of the
      intestinal epithelium. Id2-/- mice developed tumors in the small intestine.
      Histological analysis indicated that the intestinal tumors were derived from
      gastric metaplasia formed in the small intestine during development. Heterotopic
      Id2 expression in developing gastric epithelium induced a fate change to
      intestinal epithelium. Gene expression analysis revealed that foregut-enriched
      genes encoding Irx3/5 were highly induced in the midgut of Id2-/- embryos, and
      transgenic mice expressing Irx5 in the midgut endoderm developed tumors
      recapitulating the characteristics of Id2-/- mice. Altogether, our results
      demonstrate that Id2 plays a crucial role in the development of regional
      specificity in the gastrointestinal epithelium.

PMID- 29463649
TI  - Ligand-Dependent Corepressor (LCoR) Is a Rexinoid-Inhibited Peroxisome
      Proliferator-Activated Receptor gamma-Retinoid X Receptor alpha Coactivator.
AB  - The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma)
      is an essential regulator of placental development. To gain deeper insights into
      placental PPARgamma signaling, we dissected its regulation of the Muc1 promoter.
      We find that, unlike prototypic target activation by heterodimeric receptors,
      which is either stimulated by or refractory to retinoid X receptor (RXR) ligands
      (rexinoids), the induction of Muc1 by liganded PPARgamma requires RXRalpha but is
      inhibited by rexinoids. We demonstrate that this inhibition is mediated by the
      activation function 2 (AF2) domain of RXRalpha and that Muc1 activation entails
      altered AF2 structures of both PPARgamma and RXRalpha. This unique regulation of
      Muc1 reflects specific coactivation of PPARgamma-RXRalpha heterodimers by the
      transcription cofactor ligand-dependent corepressor (LCoR), corroborated by
      significant downregulation of Muc1 in Lcor-null placentas. LCoR interacts with
      PPARgamma and RXRalpha in a synergistic fashion via adjacent noncanonical protein
      motifs, and the AF2 domain of ligand-bound RXRalpha inhibits this interaction. We
      further identify the transcription factor Kruppel-like factor 6 (KLF6) as a
      critical regulator of placental development and a component of Muc1 regulation in
      cooperation with PPARgamma, RXRalpha, and LCoR. Combined, these studies reveal
      new principles and players in nuclear receptor function in general and placental
      PPARgamma signaling in particular.

PMID- 29463650
TI  - Elegant Science.
AB  - Elegance is a prized quality in science that is associated with simplicity and
      explanatory power. This essay considers the qualities that make a scientific
      model, experiment, method, or theory "elegant," with a focus on the life
      sciences. We propose a definition of elegance that includes clarity, cleverness,
      correctness, explanatory power, parsimony, and beauty. The pursuit of elegance
      can improve the quality of science, but elegance must be pursued with caution, as
      the truth is sometimes inelegant.

PMID- 29463651
TI  - N-glycosylation of Viral E Protein Is the Determinant for Vector Midgut Invasion
      by Flaviviruses.
AB  - Transmission of flaviviruses by hematophagous insects such as mosquitoes requires
      acquisition of the virus during blood feeding on the host, with midgut as the
      primary infection site. Here, we report that N-glycosylation of the E protein,
      which is conserved among most flaviviruses, is critical for the Zika virus (ZIKV)
      to invade the vector midgut by inhibiting the reactive oxygen species (ROS)
      pathway of the mosquito immune system. Our data further show that removal of the
      ZIKV E glycosylation site prevents mosquito infection by flaviviruses via the
      oral route, whereas there is no effect on infection by intrathoracic
      microinjection, which bypasses the midgut. Interestingly, the defect in infection
      of the mosquito midgut by the mutant virus through blood feeding is rescued by
      reduction of the ROS level by application of vitamin C, a well-known antioxidant.
      Therefore, our data demonstrate that ZIKV utilizes the glycosylation on the
      envelope to antagonize the vector immune defense during infection.IMPORTANCE Most
      flaviviruses, including Zika virus (ZIKV), are transmitted between hosts by
      arthropod vectors, such as mosquitoes, which acquire the virus during a blood
      meal. Here, by mutagenesis, we found a major role of the N-glycosylation of
      flavivirus E protein in its transmission circle, facilitating its survival
      against the vector immune system during invasion of the mosquito midgut while
      blood feeding on the host. In spite of the extensive studies of the involvement
      of N-glycan modification of flavivirus E protein in virus-host interactions, we
      discovered its critical role in virus-vector interaction and the evolution of
      flavivirus. Given the deleterious effects of ZIKV on human health, this study
      might have a significant impact on development of novel transmission-blocking
      strategies.

PMID- 29463652
TI  - Ethanolamine Utilization in Bacteria.
AB  - Ethanolamine (EA) is a valuable source of carbon and/or nitrogen for bacteria
      capable of its catabolism. Because it is derived from the membrane phospholipid
      phosphatidylethanolamine, it is particularly prevalent in the gastrointestinal
      tract, which is membrane rich due to turnover of the intestinal epithelium and
      the resident microbiota. Intriguingly, many gut pathogens carry the eut
      (ethanolamine utilization) genes. EA utilization has been studied for about 50
      years, with most of the early work occurring in just a couple of species of
      Enterobacteriaceae Once the metabolic pathways and enzymes were characterized by
      biochemical approaches, genetic screens were used to map the various activities
      to the eut genes. With the rise of genomics, the diversity of bacteria containing
      the eut genes and surprising differences in eut gene content were recognized.
      Some species contain nearly 20 genes and encode many accessory proteins, while
      others contain only the core catabolic enzyme. Moreover, the eut genes are
      regulated by very different mechanisms, depending on the organism and the eut
      regulator encoded. In the last several years, exciting progress has been made in
      elucidating the complex regulatory mechanisms that govern eut gene expression.
      Furthermore, a new appreciation for how EA contributes to infection and
      colonization in the host is emerging. In addition to providing an overview of EA
      related biology, this minireview will give special attention to these recent
      advances.

PMID- 29463653
TI  - Efficient and Scalable Precision Genome Editing in Staphylococcus aureus through
      Conditional Recombineering and CRISPR/Cas9-Mediated Counterselection.
AB  - Staphylococcus aureus is an important human pathogen, but studies of the organism
      have suffered from the lack of a robust tool set for its genetic and genomic
      manipulation. Here we report the development of a system for the facile and high
      throughput genomic engineering of S. aureus using single-stranded DNA (ssDNA)
      oligonucleotide recombineering coupled with clustered regularly interspaced short
      palindromic repeat (CRISPR)/Cas9-mediated counterselection. We identify
      recombinase EF2132, derived from Enterococcus faecalis, as being capable of
      integrating single-stranded DNA oligonucleotides into the S. aureus genome. We
      found that EF2132 can readily mediate recombineering across multiple
      characterized strains (3 of 3 tested) and primary clinical isolates (6 of 6
      tested), typically yielding thousands of recombinants per transformation.
      Surprisingly, we also found that some S. aureus strains are naturally
      recombinogenic at measurable frequencies when oligonucleotides are introduced by
      electroporation, even without exogenous recombinase expression. We construct a
      temperature-sensitive, two-vector system which enables conditional recombineering
      and CRISPR/Cas9-mediated counterselection in S. aureus without permanently
      introducing exogenous genetic material or unintended genetic lesions. We
      demonstrate the ability of this system to efficiently and precisely engineer
      point mutations and large single-gene deletions in the S. aureus genome and to
      yield highly enriched populations of engineered recombinants even in the absence
      of an externally selectable phenotype. By virtue of utilizing inexpensive,
      commercially synthesized synthetic DNA oligonucleotides as substrates for
      recombineering and counterselection, this system provides a scalable, versatile,
      precise, inexpensive, and generally useful tool for producing isogenic strains in
      S. aureus which will enable the high-throughput functional assessment of genome
      variation and gene function across multiple strain backgrounds.IMPORTANCE
      Engineering genetic changes in bacteria is critical to understanding the function
      of particular genes or mutations but is currently a laborious and technically
      challenging process to perform for the important human pathogen Staphylococcus
      aureus In an effort to develop methods which are rapid, easy, scalable,
      versatile, and inexpensive, here we describe a system for incorporating
      synthetic, mutagenic DNA molecules into the S. aureus genome and for eliminating
      cells that lack the engineered mutation. This method allows efficient, precise,
      and high-throughput genetic engineering of S. aureus strains and will facilitate
      studies seeking to address a variety of issues about the function of particular
      genes and specific mutations.

PMID- 29463654
TI  - Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi
      Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and
      Third-Generation Cephalosporins.
AB  - Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi,
      the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent
      in parts of Asia and Africa and are often associated with the dominant H58
      haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and
      sporadic cases of resistance to third-generation cephalosporins or azithromycin
      have also been reported. Here, we report the first large-scale emergence and
      spread of a novel S Typhi clone harboring resistance to three first-line drugs
      (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as
      fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we
      classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have
      emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of
      travel-associated XDR typhoid has recently been identified in the United Kingdom.
      Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable
      genetic clonality and sequence conservation, identified a large number of
      resistance determinants, and showed that these isolates were of haplotype H58.
      The XDR S Typhi clone encodes a chromosomally located resistance region and
      harbors a plasmid encoding additional resistance elements, including the blaCTX-M
      15 extended-spectrum beta-lactamase, and carrying the qnrS fluoroquinolone
      resistance gene. This antibiotic resistance-associated IncY plasmid exhibited
      high sequence identity to plasmids found in other enteric bacteria isolated from
      widely distributed geographic locations. This study highlights three concerning
      problems: the receding antibiotic arsenal for typhoid treatment, the ability of S
      Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid,
      and the ability of XDR clones to spread globally.IMPORTANCE Typhoid fever is a
      severe disease caused by the Gram-negative bacterium Salmonella enterica serovar
      Typhi. Antibiotic-resistant S Typhi strains have become increasingly common.
      Here, we report the first large-scale emergence and spread of a novel extensively
      drug-resistant (XDR) S Typhi clone in Sindh, Pakistan. The XDR S Typhi is
      resistant to the majority of drugs available for the treatment of typhoid fever.
      This study highlights the evolving threat of antibiotic resistance in S Typhi and
      the value of antibiotic susceptibility testing and whole-genome sequencing in
      understanding emerging infectious diseases. We genetically characterized the XDR
      S Typhi to investigate the phylogenetic relationship between these isolates and a
      global collection of S Typhi isolates and to identify multiple genes linked to
      antibiotic resistance. This S Typhi clone harbored a promiscuous antibiotic
      resistance plasmid previously identified in other enteric bacteria. The
      increasing antibiotic resistance in S Typhi observed here adds urgency to the
      need for typhoid prevention measures.

PMID- 29463655
TI  - De Novo Assembly and Phasing of Dikaryotic Genomes from Two Isolates of Puccinia
      coronata f. sp. avenae, the Causal Agent of Oat Crown Rust.
AB  - Oat crown rust, caused by the fungus Pucinnia coronata f. sp. avenae, is a
      devastating disease that impacts worldwide oat production. For much of its life
      cycle, P. coronata f. sp. avenae is dikaryotic, with two separate haploid nuclei
      that may vary in virulence genotype, highlighting the importance of understanding
      haplotype diversity in this species. We generated highly contiguous de novo
      genome assemblies of two P. coronata f. sp. avenae isolates, 12SD80 and 12NC29,
      from long-read sequences. In total, we assembled 603 primary contigs for 12SD80,
      for a total assembly length of 99.16 Mbp, and 777 primary contigs for 12NC29, for
      a total length of 105.25 Mbp; approximately 52% of each genome was assembled into
      alternate haplotypes. This revealed structural variation between haplotypes in
      each isolate equivalent to more than 2% of the genome size, in addition to about
      260,000 and 380,000 heterozygous single-nucleotide polymorphisms in 12SD80 and
      12NC29, respectively. Transcript-based annotation identified 26,796 and 28,801
      coding sequences for isolates 12SD80 and 12NC29, respectively, including about
      7,000 allele pairs in haplotype-phased regions. Furthermore, expression profiling
      revealed clusters of coexpressed secreted effector candidates, and the majority
      of orthologous effectors between isolates showed conservation of expression
      patterns. However, a small subset of orthologs showed divergence in expression,
      which may contribute to differences in virulence between 12SD80 and 12NC29. This
      study provides the first haplotype-phased reference genome for a dikaryotic rust
      fungus as a foundation for future studies into virulence mechanisms in P.
      coronata f. sp. avenaeIMPORTANCE Disease management strategies for oat crown rust
      are challenged by the rapid evolution of Puccinia coronata f. sp. avenae, which
      renders resistance genes in oat varieties ineffective. Despite the economic
      importance of understanding P. coronata f. sp. avenae, resources to study the
      molecular mechanisms underpinning pathogenicity and the emergence of new
      virulence traits are lacking. Such limitations are partly due to the obligate
      biotrophic lifestyle of P. coronata f. sp. avenae as well as the dikaryotic
      nature of the genome, features that are also shared with other important rust
      pathogens. This study reports the first release of a haplotype-phased genome
      assembly for a dikaryotic fungal species and demonstrates the amenability of
      using emerging technologies to investigate genetic diversity in populations of P.
      coronata f. sp. avenae.

PMID- 29463656
TI  - Yersinia pestis Targets the Host Endosome Recycling Pathway during the Biogenesis
      of the Yersinia-Containing Vacuole To Avoid Killing by Macrophages.
AB  - Yersinia pestis has evolved many strategies to evade the innate immune system.
      One of these strategies is the ability to survive within macrophages. Upon
      phagocytosis, Y. pestis prevents phagolysosome maturation and establishes a
      modified compartment termed the Yersinia-containing vacuole (YCV). Y. pestis
      actively inhibits the acidification of this compartment, and eventually, the YCV
      transitions from a tight-fitting vacuole into a spacious replicative vacuole. The
      mechanisms to generate the YCV have not been defined. However, we hypothesized
      that YCV biogenesis requires Y. pestis interactions with specific host factors to
      subvert normal vesicular trafficking. In order to identify these factors, we
      performed a genome-wide RNA interference (RNAi) screen to identify host factors
      required for Y. pestis survival in macrophages. This screen revealed that 71 host
      proteins are required for intracellular survival of Y. pestis Of particular
      interest was the enrichment for genes involved in endosome recycling. Moreover,
      we demonstrated that Y. pestis actively recruits Rab4a and Rab11b to the YCV in a
      type three secretion system-independent manner, indicating remodeling of the YCV
      by Y. pestis to resemble a recycling endosome. While recruitment of Rab4a was
      necessary to inhibit YCV acidification and lysosomal fusion early during
      infection, Rab11b appeared to contribute to later stages of YCV biogenesis. We
      also discovered that Y. pestis disrupts global host endocytic recycling in
      macrophages, possibly through sequestration of Rab11b, and this process is
      required for bacterial replication. These data provide the first evidence that Y.
      pestis targets the host endocytic recycling pathway to avoid phagolysosomal
      maturation and generate the YCV.IMPORTANCEYersinia pestis can infect and survive
      within macrophages. However, the mechanisms that the bacterium use to subvert
      killing by these phagocytes have not been defined. To provide a better
      understanding of these mechanisms, we used an RNAi approach to identify host
      factors required for intracellular Y. pestis survival. This approach revealed
      that the host endocytic recycling pathway is essential for Y. pestis to avoid
      clearance by the macrophage. We further demonstrate that Y. pestis remodels the
      phagosome to resemble a recycling endosome, allowing the bacterium to avoid the
      normal phagolysosomal maturation pathway. Moreover, we show that infection with
      Y. pestis disrupts normal recycling in the macrophage and that disruption is
      required for bacterial replication. These findings provide the first evidence
      that Y. pestis targets the host endocytic recycling pathway in order to evade
      killing by macrophages.

PMID- 29463657
TI  - The Essential Genome of Escherichia coli K-12.
AB  - Transposon-directed insertion site sequencing (TraDIS) is a high-throughput
      method coupling transposon mutagenesis with short-fragment DNA sequencing. It is
      commonly used to identify essential genes. Single gene deletion libraries are
      considered the gold standard for identifying essential genes. Currently, the
      TraDIS method has not been benchmarked against such libraries, and therefore, it
      remains unclear whether the two methodologies are comparable. To address this, a
      high-density transposon library was constructed in Escherichia coli K-12.
      Essential genes predicted from sequencing of this library were compared to
      existing essential gene databases. To decrease false-positive identification of
      essential genes, statistical data analysis included corrections for both gene
      length and genome length. Through this analysis, new essential genes and genes
      previously incorrectly designated essential were identified. We show that manual
      analysis of TraDIS data reveals novel features that would not have been detected
      by statistical analysis alone. Examples include short essential regions within
      genes, orientation-dependent effects, and fine-resolution identification of
      genome and protein features. Recognition of these insertion profiles in
      transposon mutagenesis data sets will assist genome annotation of less well
      characterized genomes and provides new insights into bacterial physiology and
      biochemistry.IMPORTANCE Incentives to define lists of genes that are essential
      for bacterial survival include the identification of potential targets for
      antibacterial drug development, genes required for rapid growth for exploitation
      in biotechnology, and discovery of new biochemical pathways. To identify
      essential genes in Escherichia coli, we constructed a transposon mutant library
      of unprecedented density. Initial automated analysis of the resulting data
      revealed many discrepancies compared to the literature. We now report more
      extensive statistical analysis supported by both literature searches and detailed
      inspection of high-density TraDIS sequencing data for each putative essential
      gene for the E. coli model laboratory organism. This paper is important because
      it provides a better understanding of the essential genes of E. coli, reveals the
      limitations of relying on automated analysis alone, and provides a new standard
      for the analysis of TraDIS data.

PMID- 29463658
TI  - Functional and Expression Analyses of the Pneumocystis MAT Genes Suggest Obligate
      Sexuality through Primary Homothallism within Host Lungs.
AB  - Fungi of the genus Pneumocystis are obligate parasites that colonize mammals'
      lungs and are host species specific. Pneumocystis jirovecii and Pneumocystis
      carinii infect, respectively, humans and rats. They can turn into opportunistic
      pathogens in immunosuppressed hosts, causing severe pneumonia. Their cell cycle
      is poorly known, mainly because of the absence of an established method of
      culture in vitro It is thought to include both asexual and sexual phases.
      Comparative genomic analysis suggested that their mode of sexual reproduction is
      primary homothallism involving a single mating type (MAT) locus encompassing plus
      and minus genes (matMc, matMi, and matPi; Almeida et al., mBio 6:e02250-14,
      2015). Thus, each strain would be capable of sexual reproduction alone (self
      fertility). However, this is a working hypothesis derived from computational
      analyses that is, in addition, based on the genome sequences of single isolates.
      Here, we tested this hypothesis in the wet laboratory. The function of the P.
      jirovecii and P. carinii matMc genes was ascertained by restoration of
      sporulation in the corresponding mutant of fission yeast. Using PCR, we found the
      same single MAT locus in all P. jirovecii isolates and showed that all three MAT
      genes are often concomitantly expressed during pneumonia. Extensive homology
      searches did not identify other types of MAT transcription factors in the genomes
      or cis-acting motifs flanking the MAT locus that could have been involved in MAT
      switching or silencing. Our observations suggest that Pneumocystis sexuality
      through primary homothallism is obligate within host lungs to complete the cell
      cycle, i.e., produce asci necessary for airborne transmission to new
      hosts.IMPORTANCE Fungi of the genus Pneumocystis colonize the lungs of mammals.
      In immunosuppressed human hosts, Pneumocystis jirovecii may cause severe
      pneumonia that can be fatal. This disease is one of the most frequent life
      threatening invasive fungal infections in humans. The analysis of the genome
      sequences of these uncultivable pathogens suggested that their sexual
      reproduction involves a single partner (self-fertilization). Here, we report
      laboratory experiments that support this hypothesis. The function of the three
      genes responsible for sexual differentiation was ascertained by the restoration
      of sexual reproduction in the corresponding mutant of another fungus. As
      predicted by self-fertilization, all P. jirovecii isolates harbored the same
      three genes that were often concomitantly expressed within human lungs during
      infection. Our observations suggest that the sexuality of these pathogens relies
      on the self-fertility of each isolate and is obligate within host lungs to
      complete the cell cycle and allow dissemination of the fungus to new hosts.

PMID- 29463659
TI  - A Near-Complete Haplotype-Phased Genome of the Dikaryotic Wheat Stripe Rust
      Fungus Puccinia striiformis f. sp. tritici Reveals High Interhaplotype Diversity.
AB  - A long-standing biological question is how evolution has shaped the genomic
      architecture of dikaryotic fungi. To answer this, high-quality genomic resources
      that enable haplotype comparisons are essential. Short-read genome assemblies for
      dikaryotic fungi are highly fragmented and lack haplotype-specific information
      due to the high heterozygosity and repeat content of these genomes. Here, we
      present a diploid-aware assembly of the wheat stripe rust fungus Puccinia
      striiformis f. sp. tritici based on long reads using the FALCON-Unzip assembler.
      Transcriptome sequencing data sets were used to infer high-quality gene models
      and identify virulence genes involved in plant infection referred to as
      effectors. This represents the most complete Puccinia striiformis f. sp. tritici
      genome assembly to date (83 Mb, 156 contigs, N50 of 1.5 Mb) and provides phased
      haplotype information for over 92% of the genome. Comparisons of the phase blocks
      revealed high interhaplotype diversity of over 6%. More than 25% of all genes
      lack a clear allelic counterpart. When we investigated genome features that
      potentially promote the rapid evolution of virulence, we found that candidate
      effector genes are spatially associated with conserved genes commonly found in
      basidiomycetes. Yet, candidate effectors that lack an allelic counterpart are
      more distant from conserved genes than allelic candidate effectors and are less
      likely to be evolutionarily conserved within the P. striiformis species complex
      and Pucciniales In summary, this haplotype-phased assembly enabled us to discover
      novel genome features of a dikaryotic plant-pathogenic fungus previously hidden
      in collapsed and fragmented genome assemblies.IMPORTANCE Current representations
      of eukaryotic microbial genomes are haploid, hiding the genomic diversity
      intrinsic to diploid and polyploid life forms. This hidden diversity contributes
      to the organism's evolutionary potential and ability to adapt to stress
      conditions. Yet, it is challenging to provide haplotype-specific information at a
      whole-genome level. Here, we take advantage of long-read DNA sequencing
      technology and a tailored-assembly algorithm to disentangle the two haploid
      genomes of a dikaryotic pathogenic wheat rust fungus. The two genomes display
      high levels of nucleotide and structural variations, which lead to allelic
      variation and the presence of genes lacking allelic counterparts. Nonallelic
      candidate effector genes, which likely encode important pathogenicity factors,
      display distinct genome localization patterns and are less likely to be
      evolutionary conserved than those which are present as allelic pairs. This
      genomic diversity may promote rapid host adaptation and/or be related to the age
      of the sequenced isolate since last meiosis.

PMID- 29463662
TI  - In This Issue of Diabetes Care.

PMID- 29463660
TI  - Novel Segment- and Host-Specific Patterns of Enteroaggregative Escherichia coli
      Adherence to Human Intestinal Enteroids.
AB  - Enteroaggregative Escherichia coli (EAEC) is an important diarrheal pathogen and
      a cause of both acute and chronic diarrhea. It is a common cause of pediatric
      bacterial diarrhea in developing countries. Despite its discovery in 1987, the
      intestinal tropism of the pathogen remains unknown. Cell lines used to study EAEC
      adherence include the HEp-2, T-84, and Caco-2 lines, but they exhibit abnormal
      metabolism and large variations in gene expression. Animal models either do not
      faithfully manifest human clinical symptoms or are cumbersome and expensive.
      Using human intestinal enteroids derived from all four segments of the human
      intestine, we find that EAEC demonstrates aggregative adherence to duodenal and
      ileal enteroids, with donor-driven differences driving a sheet-like and layered
      pattern. This contrasts with the colon, where segment-specific tropisms yielded a
      mesh-like adherence pattern dominated by interconnecting filaments. Very little
      to no aggregative adherence to jejunal enteroids was observed, regardless of the
      strain or donor, in contrast to a strong duodenal association across all donors
      and strains. These unique patterns of intestinal segment- or donor-specific
      adherence, but not the overall numbers of associated bacteria, were dependent on
      the major subunit protein of aggregative adherence fimbriae II (AafA), implying
      that the morphology of adherent clusters and the overall intestinal cell
      association of EAEC occur by different mechanisms. Our results suggest that we
      must give serious consideration to inter- and intrapatient variations in what is
      arguably the first step in pathogenesis, that of adherence, when considering the
      clinical manifestation of these infections.IMPORTANCE EAEC is a leading cause of
      pediatric bacterial diarrhea and a common cause of diarrhea among travelers and
      immunocompromised individuals. Heterogeneity in EAEC strains and lack of a good
      model system are major roadblocks to the understanding of its pathogenesis.
      Utilizing human intestinal enteroids to study the adherence of EAEC, we
      demonstrate that unique patterns of adherence are largely driven by unidentified
      factors present in different intestinal segments and from different donors. These
      patterns are also dependent on aggregative adherence fimbriae II encoded by EAEC.
      These results imply that we must also consider the contribution of the host to
      understand the pathogenesis of EAEC-induced inflammation and diarrhea.

PMID- 29463663
TI  - American Diabetes Association's Standards of Care: A Paradigm Shift in the
      Dissemination of Information.

PMID- 29463664
TI  - Are All Patients With Type 1 Diabetes Destined for Dialysis if They Live Long
      Enough? Probably Not.

PMID- 29463661
TI  - Microbial Functional Gene Diversity Predicts Groundwater Contamination and
      Ecosystem Functioning.
AB  - Contamination from anthropogenic activities has significantly impacted Earth's
      biosphere. However, knowledge about how environmental contamination affects the
      biodiversity of groundwater microbiomes and ecosystem functioning remains very
      limited. Here, we used a comprehensive functional gene array to analyze
      groundwater microbiomes from 69 wells at the Oak Ridge Field Research Center (Oak
      Ridge, TN), representing a wide pH range and uranium, nitrate, and other
      contaminants. We hypothesized that the functional diversity of groundwater
      microbiomes would decrease as environmental contamination (e.g., uranium or
      nitrate) increased or at low or high pH, while some specific populations capable
      of utilizing or resistant to those contaminants would increase, and thus, such
      key microbial functional genes and/or populations could be used to predict
      groundwater contamination and ecosystem functioning. Our results indicated that
      functional richness/diversity decreased as uranium (but not nitrate) increased in
      groundwater. In addition, about 5.9% of specific key functional populations
      targeted by a comprehensive functional gene array (GeoChip 5) increased
      significantly (P < 0.05) as uranium or nitrate increased, and their changes could
      be used to successfully predict uranium and nitrate contamination and ecosystem
      functioning. This study indicates great potential for using microbial functional
      genes to predict environmental contamination and ecosystem functioning.IMPORTANCE
      Disentangling the relationships between biodiversity and ecosystem functioning is
      an important but poorly understood topic in ecology. Predicting ecosystem
      functioning on the basis of biodiversity is even more difficult, particularly
      with microbial biomarkers. As an exploratory effort, this study used key
      microbial functional genes as biomarkers to provide predictive understanding of
      environmental contamination and ecosystem functioning. The results indicated that
      the overall functional gene richness/diversity decreased as uranium increased in
      groundwater, while specific key microbial guilds increased significantly as
      uranium or nitrate increased. These key microbial functional genes could be used
      to successfully predict environmental contamination and ecosystem functioning.
      This study represents a significant advance in using functional gene markers to
      predict the spatial distribution of environmental contaminants and ecosystem
      functioning toward predictive microbial ecology, which is an ultimate goal of
      microbial ecology.

PMID- 29463665
TI  - Assessing Health-Related Quality of Life in Patients With Diabetic Foot Disease:
      Why Is It Important and How Can We Improve? The 2017 Roger E. Pecoraro Award
      Lecture.
AB  - Patient-reported outcomes (PROs) have become an important subject in the area of
      diabetes-related foot complications. Self-reported health-related quality of life
      (HRQOL) surveys can provide a generic measure of overall health (global) and can
      be disease specific (i.e., diabetes) or even region specific (i.e., lower
      extremity function). Analysis of PRO measures utilizing validated instruments
      allows health care providers to determine whether medical and surgical treatments
      are providing patients with the highest level of outcome possible and are
      actually improving HRQOL. The 36-item Short Form (SF-36), EuroQol five-dimension
      questionnaire (EQ-5D-5L), and Foot and Ankle Ability Measure (FAAM) are examples
      of commonly used HRQOL surveys. Low HRQOL has been associated with higher rates
      of hospital admission and mortality in patients with diabetes. Previous studies
      have demonstrated that patients with diabetes-related foot disease have low self
      reported physical quality of life but do not typically report low mental quality
      of life. The impact of mental quality of life may be underestimated in these
      patients using the SF-36. In this article, we will discuss several widely used
      outcome instruments used to measure patient HRQOL and the impact of diabetic foot
      disease on HRQOL. As health care providers, we must continue to adjust and modify
      our treatments to achieve the best patient outcomes and associated high quality
      of life. Assessing PROs will become increasingly important as health care systems
      transition from a volume-based reimbursement model to a value-based model.

PMID- 29463666
TI  - Gastrointestinal Symptoms in Diabetes: Prevalence, Assessment, Pathogenesis, and
      Management.
AB  - If you haven't measured something, you really don't know much about it.-Karl
      Pearson (attributed)Gastrointestinal (GI) symptoms represent an important and
      often unappreciated cause of morbidity in diabetes, although the significance of
      this burden across the spectrum of patients and the underlying pathophysiology,
      including the relationship of symptoms with glycemic control, remain poorly
      defined. The relevance of GI symptoms and the necessity for their accurate
      assessment have increased with the greater focus on the gut as a therapeutic
      target for glucose lowering. This review addresses the prevalence, assessment,
      pathogenesis, and management of GI symptoms in diabetes, beginning with broad
      principles and then focusing on specific segments of the GI tract. We initially
      performed a literature search of PubMed by using synonyms and combinations of the
      following search terms: "gastrointestinal symptoms", "diabetes", "prevalence",
      "pathogenesis", "diagnosis", and "management". We restricted the search results
      to English only. Review papers and meta-analyses are presented as the highest
      level of evidence where possible followed by randomized controlled trials,
      uncontrolled trials, retrospective and observational data, and expert opinion.

PMID- 29463667
TI  - Anti-Programmed Death 1 (PD-1) Antibodies and the Pancreas: A Diabetic Storm
      Ahead?

PMID- 29463669
TI  - Comment on Russell-Jones et al. Diabetes Care 2017;40:943-950. Comment on
      Bowering et al. Diabetes Care 2017;40:951-957.

PMID- 29463670
TI  - Response to Comment on Russell-Jones et al. Diabetes Care 2017;40:943-950.
      Comment on Bowering et al. Diabetes Care 2017;40:951-957.

PMID- 29463671
TI  - Comment on Young-Hyman et al. Psychosocial Care for People With Diabetes: A
      Position Statement of the American Diabetes Association. Diabetes Care
      2016;39:2126-2140.

PMID- 29463672
TI  - Response to Comment on Young-Hyman et al. Psychosocial Care for People With
      Diabetes: A Position Statement of the American Diabetes Association. Diabetes
      Care 2016;39:2126-2140.

PMID- 29463673
TI  - Comment on Jaiswal et al. Prevalence of and Risk Factors for Diabetic Peripheral
      Neuropathy in Youth With Type 1 and Type 2 Diabetes: SEARCH for Diabetes in Youth
      Study. Diabetes Care 2017;40:1226-1232.

PMID- 29463674
TI  - Response to Comment on Jaiswal et al. Prevalence of and Risk Factors for Diabetic
      Peripheral Neuropathy in Youth With Type 1 and Type 2 Diabetes: SEARCH for
      Diabetes in Youth Study. Diabetes Care 2017;40:1226-1232.

PMID- 29463675
TI  - Comment on Ohkuma et al. Cardiac Stress and Inflammatory Markers as Predictors of
      Heart Failure in Patients With Type 2 Diabetes: The ADVANCE Trial. Diabetes Care
      2017;40:1203-1209.

PMID- 29463676
TI  - Response to Comment on Ohkuma et al. Cardiac Stress and Inflammatory Markers as
      Predictors of Heart Failure in Patients With Type 2 Diabetes: The ADVANCE Trial.
      Diabetes Care 2017;40:1203-1209.

PMID- 29463677
TI  - An unexpected link between fatty acid synthase and cholesterol synthesis in
      proinflammatory macrophage activation.
AB  - Different immune activation states require distinct metabolic features and
      activities in immune cells. For instance, inhibition of fatty acid synthase
      (FASN), which catalyzes the synthesis of long-chain fatty acids, prevents the
      proinflammatory response in macrophages; however, the precise role of this enzyme
      in this response remains poorly defined. Consistent with previous studies, we
      found here that FASN is essential for lipopolysaccharide-induced, Toll-like
      receptor (TLR)-mediated macrophage activation. Interestingly, only agents that
      block FASN upstream of acetoacetyl-CoA synthesis, including the well
      characterized FASN inhibitor C75, inhibited TLR4 signaling, while those acting
      downstream had no effect. We found that acetoacetyl-CoA could overcome C75's
      inhibitory effect, whereas other FASN metabolites, including palmitate, did not
      prevent C75-mediated inhibition. This suggested an unexpected role for
      acetoacetyl-CoA in inflammation that is independent of its role in palmitate
      synthesis. Our evidence further suggested that acetoacetyl-CoA arising from FASN
      activity promotes cholesterol production, indicating a surprising link between
      fatty acid synthesis and cholesterol synthesis. We further demonstrate that this
      process is required for TLR4 to enter lipid rafts and facilitate TLR4 signaling.
      In conclusion, we have uncovered an unexpected link between FASN and cholesterol
      synthesis that appears to be required for TLR signal transduction and
      proinflammatory macrophage activation.

PMID- 29463678
TI  - Structural basis of sterol binding and transport by a yeast StARkin domain.
AB  - The StARkin superfamily comprises proteins with steroidogenic acute regulatory
      protein-related lipid transfer (StART) domains that are implicated in
      intracellular, non-vesicular lipid transport. A new family of membrane-anchored
      StARkins was recently identified, including six members, Lam1-Lam6, in the yeast
      Saccharomyces cerevisiae. Lam1-Lam4 are anchored to the endoplasmic reticulum
      (ER) membrane at sites where the ER is tethered to the plasma membrane and
      proposed to be involved in sterol homeostasis in yeast. To better understand the
      biological roles of these proteins, we carried out a structure-function analysis
      of the second StARkin domain of Lam4, here termed Lam4S2. NMR experiments
      indicated that Lam4S2 undergoes specific conformational changes upon binding
      sterol, and fluorescence-based assays revealed that it catalyzes sterol transport
      between vesicle populations in vitro, exhibiting a preference for vesicles
      containing anionic lipids. Using such vesicles, we found that sterols are
      transported at a rate of ~50 molecules per Lam4S2 per minute. Crystal structures
      of Lam4S2, with and without bound sterol, revealed a largely hydrophobic but
      surprisingly accessible sterol-binding pocket with the 3-OH group of the sterol
      oriented toward its base. Single or multiple alanine or aspartic acid
      replacements of conserved lysine residues in a basic patch on the surface of
      Lam4S2 near the likely sterol entry/egress site strongly attenuated sterol
      transport. Our results suggest that Lam4S2 engages anionic membranes via a basic
      surface patch, enabling "head-first" entry of sterol into the binding pocket
      followed by partial closure of the entryway. Reversal of these steps enables
      sterol egress.

PMID- 29463679
TI  - Substrate clustering potently regulates the activity of WW-HECT domain-containing
      ubiquitin ligases.
AB  - The Nedd4 family of HECT domain-containing E3 ligases ubiquitinate many
      transcription factors and signaling proteins, and their activity is tightly
      regulated. Normally, intramolecular interactions curb the catalytic activity of
      the HECT domain, but these can be broken by the binding of PY motifs, found on
      substrate molecules and adaptors, to the WW domains characteristic of this E3
      ligase family. This raises the prospect of substrates automatically activating
      the ligases, frustrating the purpose of ligase regulation. Here we show that
      soluble protein substrates and adaptors such as alpha arrestins, even with
      multiple PY elements, cannot activate ligase activity efficiently. However, we
      found that polymerization or membrane tethering of these substrates dramatically
      increases the ligase activity both in vivo and in vitro Aggregation of luciferase
      containing substrates upon heat shock had a similar effect and could also expose
      cryptic PY elements in the substrates. We inferred that ligase activation
      critically requires a substantial array of clustered PY motifs and that the
      formation of such arrays on membranes or in polymeric aggregates may be an
      essential step in this mode of ligase regulation. We conclude that recruitment of
      alpha arrestins to membrane receptors and aggregation of unstable proteins after
      heat shock may be physiologically relevant mechanisms for triggering
      ubiquitination by Nedd4 family HECT domain-containing E3 ligases.

PMID- 29463680
TI  - The actin filament twist changes abruptly at boundaries between bare and cofilin
      decorated segments.
AB  - Cofilin/ADF proteins are actin-remodeling proteins, essential for actin
      disassembly in various cellular processes, including cell division, intracellular
      transport, and motility. Cofilins bind actin filaments cooperatively and sever
      them preferentially at boundaries between bare and cofilin-decorated (cofilactin)
      segments. The cooperative binding to actin has been proposed to originate from
      conformational changes that propagate allosterically from clusters of bound
      cofilin to bare actin segments. Estimates of the lengths over which these
      cooperative conformational changes propagate vary dramatically, ranging from 2 to
      >100 subunits. Here, we present a general, structure-based method for detecting
      from cryo-EM micrographs small variations in filament geometry (i.e. twist) with
      single-subunit precision. How these variations correlate with regulatory protein
      occupancy reveals how far allosteric, conformational changes propagate along
      filaments. We used this method to determine the effects of cofilin on the actin
      filament twist. Our results indicate that cofilin-induced changes in filament
      twist propagate only 1-2 subunits from the boundary into the bare actin segment,
      independently of the boundary polarity (i.e. irrespective of whether or not the
      bare actin segment flanks the pointed or barbed-end side of the boundary) and the
      pyrene fluorophore labeling of actin. These observations indicate that the
      filament twist changes abruptly at boundaries between bare and cofilin-decorated
      segments, thereby constraining mechanistic models of cooperative actin filament
      interactions and severing by cofilin. The methods presented here extend the
      capability of cryo-EM to analyze biologically relevant deviations from helical
      symmetry in actin as well as other classes of linear polymers.

PMID- 29463682
TI  - Metabolism in pluripotency: Both driver and passenger?
AB  - Pluripotent stem cells (PSCs) are highly proliferative cells characterized by
      robust metabolic demands to power rapid division. For many years considered a
      passive component or "passenger" of cell fate determination, cell metabolism is
      now starting to take center stage as a driver of cell fate outcomes. This review
      provides an update and analysis of our current understanding of PSC metabolism
      and its role in self-renewal, differentiation, and somatic cell reprogramming to
      pluripotency. Moreover, we present evidence on the active roles metabolism plays
      in shaping the epigenome to influence patterns of gene expression that may model
      key features of early embryonic development.

PMID- 29463681
TI  - Bromodomain-containing protein 4-independent transcriptional activation by
      autoimmune regulator (AIRE) and NF-kappaB.
AB  - Autoimmune regulator (AIRE) and nuclear factor-kappaB (NF-kappaB) are
      transcription factors (TFs) that direct the expression of individual genes and
      gene clusters. Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator
      that recognizes and binds to acetylated histones. BRD4 also has been reported to
      promote interactions between the positive transcription elongation factor b (P
      TEFb) and AIRE or P-TEFb and NF-kappaB subunit p65. Here, we report that AIRE and
      p65 bind to P-TEFb independently of BRD4. JQ1, a compound that disrupts
      interactions between BRD4 and acetylated proteins, does not decrease
      transcriptional activities of AIRE or p65. Moreover, siRNA-mediated inactivation
      of BRD4 alone or in combination with JQ1 had no effects on AIRE- and NF-kappaB
      targeted genes on plasmids and in chromatin and on interactions between P-TEFb
      and AIRE or NF-kappaB. Finally, ChIP experiments revealed that recruitment of P
      TEFb to AIRE or p65 to transcription complexes was independent of BRD4. We
      conclude that direct interactions between AIRE, NF-kappaB, and P-TEFb result in
      efficient transcription of their target genes.

PMID- 29463683
TI  - Peer review policies in medical student journals.

PMID- 29463684
TI  - Strategy to reduce E. coli bacteraemia based on cohort data from a London
      teaching hospital.
AB  - BACKGROUND AND AIM: In 2017, National Health Service Improvement set a 10%
      reduction target for Escherichia coli bacteraemia by 2018, followed by a 50%
      reduction in healthcare-associated Gram-negative bacteraemias by 2022. We
      analysed consecutive cases of E. coli bacteraemia and devised a strategy to
      achieve these targets. METHODS: From December 2012 to November 2013, demographic,
      clinical and microbiological data were prospectively collected on all patients
      with bacteraemia at the Royal London Hospital in East London, UK. RESULTS: There
      were 594 significant bacteraemic episodes and 207 (34.8%) were E. coli. Twenty
      four (11.6%) of the E. coli isolates were extended spectrum beta-lactamase
      producers, 22 (10.6%) gentamicin resistant and 2 (1.0%) amikacin resistant. The
      three most common sites of infection were pyelonephritis 105 (56.7%), catheter
      associated urinary tract infection 22 (10.6%), and other medical devices and
      procedures that cause bacteraemia 32 (15.5%). In the pyelonephritis group,
      trimethoprim resistance in urinary isolates was 16/47 (34.0%) compared with 3/47
      (6.4%) for nitrofurantoin. Twelve months postbacteraemia, recurrent bacteraemia
      rates were 10/105 (9.5%). There were 44 medical device-associated E. coli
      bacteraemias, and 22 (50%) were urinary catheter associated. There were 10
      patients with E. coli bacteraemia caused by procedures, seven genitourinary or
      biliary tract instrumentation and three postgastrointestinal surgery. CONCLUSION:
      E. coli bacteraemias related to urosepsis could have been prevented by better
      empirical treatment and targeted prophylaxis. Urinary catheter quality
      improvement programmes should contribute to a further reduction. For patients
      undergoing high-risk urinary or biliary tract procedures or device manipulation,
      we advocate single-dose amikacin prophylaxis.

PMID- 29463685
TI  - Correction for McPeak et al., "Myeloid Cell-Specific Knockout of NFI-A Improves
      Sepsis Survival".

PMID- 29463686
TI  - Correction for Wu et al., "Salmonella Utilizes Zinc To Subvert Antimicrobial Host
      Defense of Macrophages via Modulation of NF-kappaB Signaling".

PMID- 29463687
TI  - Comment on "gammadelta T Cells Are Required for the Induction of Sterile Immunity
      during Irradiated Sporozoite Vaccinations".

PMID- 29463688
TI  - Response to Comment on "gammadelta T Cells Are Required for the Induction of
      Sterile Immunity during Irradiated Sporozoite Vaccinations".

PMID- 29463689
TI  - The Chemical Elucidation of Slow-Reacting Substance: Bronchospasm and Beyond.

PMID- 29463690
TI  - Pillars Article: Leukotriene C: A Slow-Reacting Substance from Murine Mastocytoma
      Cells. Proc. Natl. Acad. Sci. USA. 1979. 76: 4275-4279.

PMID- 29463692
TI  - Prophylactic Antibiotic Use in COPD and the Potential Anti-Inflammatory
      Activities of Antibiotics.
AB  - Antibiotics have previously demonstrated anti-inflammatory properties, and they
      have been linked to therapeutic benefit in several pulmonary conditions that
      feature inflammation. Previous research suggests that these anti-inflammatory
      properties may be beneficial in the treatment of COPD. This review assesses the
      potential benefit of prophylactic, long-term, and low-dose antibiotic therapy in
      COPD, and whether any effects seen are anti-inflammatory in nature. Randomized,
      controlled trials comparing antibiotic therapy with placebo in subjects with
      stable COPD were evaluated. Twelve trials involving 3,784 participants and a
      range of antibiotics were included: azithromycin (6 studies, 1,972 participants),
      clarithromycin (1 study, 67 participants), erythromycin (3 studies, 254
      participants), roxithromycin (1 study, 191 participants), and moxifloxacin (2
      studies, 1,198 participants). In vitro, in vivo, and ex vivo experimental study
      designs exploring the mechanisms via which antibiotics may act in subjects with
      stable COPD were evaluated. Azithromycin and erythromycin showed the greatest
      effect in subjects with COPD, with evidence suggesting improvement in
      exacerbation-related outcomes and health status, as measured by the St George
      Respiratory Questionnaire. An increase in antibiotic resistance was reported in 2
      studies. The macrolide class of antibiotics exhibited convincing anti
      inflammatory properties with relevance to COPD, implicating several pathways as
      potential mechanisms of action. In conclusion, the therapeutic benefit of
      macrolide antibiotics in subjects with stable COPD is consistent with anti
      inflammatory properties, and macrolides should be considered as a potential
      therapy in COPD. Safety concerns regarding antibiotic resistance need to be
      addressed before widespread use in clinical practice.

PMID- 29463691
TI  - Sepsis-Induced T Cell Immunoparalysis: The Ins and Outs of Impaired T Cell
      Immunity.
AB  - Sepsis results in a deluge of pro- and anti-inflammatory cytokines, leading to
      lymphopenia and chronic immunoparalysis. Sepsis-induced long-lasting
      immunoparalysis is defined, in part, by impaired CD4 and CD8 alphabeta T cell
      responses in the postseptic environment. The dysfunction in T cell immunity
      affects naive, effector, and memory T cells and is not restricted to classical
      alphabeta T cells. Although sepsis-induced severe and transient lymphopenia is a
      contributory factor to diminished T cell immunity, T cell-intrinsic and 
      extrinsic factors/mechanisms also contribute to impaired T cell function. In this
      review, we summarize the current knowledge of how sepsis quantitatively and
      qualitatively impairs CD4 and CD8 T cell immunity of classical and nonclassical T
      cell subsets and discuss current therapeutic approaches being developed to boost
      the recovery of T cell immunity postsepsis induction.

PMID- 29463693
TI  - Content analysis of requests for religious exemptions from a mandatory influenza
      vaccination program for healthcare personnel.
AB  - OBJECTIVE: Having failed to achieve adequate influenza vaccination rates among
      employees through voluntary programmes, healthcare organisations have adopted
      mandatory ones. Some programmes permit religious exemptions, but little is known
      about who requests religious objections or why. METHODS: Content analysis of
      applications for religious exemptions from influenza vaccination at a free
      standing children's hospital in Cincinnati, Ohio, USA during the 2014-2015
      influenza season. RESULTS: Twelve of 15 260 (0.08%) employees submitted
      applications requesting religious exemptions. Requestors included both clinical
      and non-clinical employees. All requestors voluntarily identified their religious
      affiliation, and most were Christian (n=9). Content analysis identified six
      categories of reasons used to justify an exemption: risks/benefits,
      ethical/political, lack of direct patient contact, providence, purity and
      sanctity of life. Individuals articulated reasons in 1-5 (mean 2.6) categories.
      The most frequently cited category (n=9) was purity; the vaccine and/or its mode
      of administration were impure, or receiving the vaccine would make the individual
      impure. Two individuals asserted that the vaccine contained cells derived from
      aborted human fetuses. Individuals (n=6) also volunteered information supporting
      the sincerity of their beliefs including distress over previous vaccination and
      examples of behaviour consistent with their specific objection or their general
      religious commitment. All requests were approved. CONCLUSIONS: Less than 0.1% of
      employees requested religious exemptions. Partnering with religious leaders and
      carefully correcting erroneous information may help address requestors' concerns.

PMID- 29463694
TI  - Desynchrony between brain and peripheral clocks caused by CK1delta/epsilon
      disruption in GABA neurons does not lead to adverse metabolic outcomes.
AB  - Circadian disruption as a result of shift work is associated with adverse
      metabolic consequences. Internal desynchrony between the phase of the
      suprachiasmatic nuclei (SCN) and peripheral clocks is widely believed to be a
      major factor contributing to these adverse consequences, but this hypothesis has
      never been tested directly. A GABAergic Cre driver combined with conditional
      casein kinase mutations (Vgat-Cre+CK1deltafl/flepsilonfl/+ ) was used to lengthen
      the endogenous circadian period in GABAergic neurons, including the SCN, but not
      in peripheral tissues, to create a Discordant mouse model. These mice had a long
      (27.4 h) behavioral period to which peripheral clocks entrained in vivo, albeit
      with an advanced phase (~6 h). Thus, in the absence of environmental timing cues,
      these mice had internal desynchrony between the SCN and peripheral clocks.
      Surprisingly, internal desynchrony did not result in obesity in this model.
      Instead, Discordant mice had reduced body mass compared with Cre-negative
      controls on regular chow and even when challenged with a high-fat diet.
      Similarly, internal desynchrony failed to induce glucose intolerance or disrupt
      body temperature and energy expenditure rhythms. Subsequently, a lighting cycle
      of 2-h light/23.5-h dark was used to create a similar internal desynchrony state
      in both genotypes. Under these conditions, Discordant mice maintained their lower
      body mass relative to controls, suggesting that internal desynchrony did not
      cause the lowered body mass. Overall, our results indicate that internal
      desynchrony does not necessarily lead to metabolic derangements and suggest that
      additional mechanisms contribute to the adverse metabolic consequences observed
      in circadian disruption protocols.

PMID- 29463695
TI  - Climate-mediated hybrid zone movement revealed with genomics, museum collection,
      and simulation modeling.
AB  - Climate-mediated changes in hybridization will dramatically alter the genetic
      diversity, adaptive capacity, and evolutionary trajectory of interbreeding
      species. Our ability to predict the consequences of such changes will be key to
      future conservation and management decisions. Here we tested through simulations
      how recent warming (over the course of a 32-y period) is affecting the geographic
      extent of a climate-mediated developmental threshold implicated in maintaining a
      butterfly hybrid zone (Papilio glaucus and Papilio canadensis; Lepidoptera:
      Papilionidae). These simulations predict a 68-km shift of this hybrid zone. To
      empirically test this prediction, we assessed genetic and phenotypic changes
      using contemporary and museum collections and document a 40-km northward shift of
      this hybrid zone. Interactions between the two species appear relatively
      unchanged during hybrid zone movement. We found no change in the frequency of
      hybridization, and regions of the genome that experience little to no
      introgression moved largely in concert with the shifting hybrid zone. Model
      predictions based on climate scenarios predict this hybrid zone will continue to
      move northward, but with substantial spatial heterogeneity in the velocity (55
      144 km/1  degrees C), shape, and contiguity of movement. Our findings suggest
      that the presence of nonclimatic barriers (e.g., genetic incompatibilities)
      and/or nonlinear responses to climatic gradients may preserve species boundaries
      as the species shift. Further, we show that variation in the geography of hybrid
      zone movement could result in evolutionary responses that differ for
      geographically distinct populations spanning hybrid zones, and thus have
      implications for the conservation and management of genetic diversity.

PMID- 29463696
TI  - Genetic rescue of lineage-balanced blood cell production reveals a crucial role
      for STAT3 antiinflammatory activity in hematopoiesis.
AB  - Blood cell formation must be appropriately maintained throughout life to provide
      robust immune function, hemostasis, and oxygen delivery to tissues, and to
      prevent disorders that result from over- or underproduction of critical lineages.
      Persistent inflammation deregulates hematopoiesis by damaging hematopoietic stem
      and progenitor cells (HSPCs), leading to elevated myeloid cell output and
      eventual bone marrow failure. Nonetheless, antiinflammatory mechanisms that
      protect the hematopoietic system are understudied. The transcriptional regulator
      STAT3 has myriad roles in HSPC-derived populations and nonhematopoietic tissues,
      including a potent antiinflammatory function in differentiated myeloid cells.
      STAT3 antiinflammatory activity is facilitated by STAT3-mediated transcriptional
      repression of Ube2n, which encodes the E2 ubiquitin-conjugating enzyme Ubc13
      involved in proinflammatory signaling. Here we demonstrate a crucial role for
      STAT3 antiinflammatory activity in preservation of HSPCs and lineage-balanced
      hematopoiesis. Conditional Stat3 removal from the hematopoietic system led to
      depletion of the bone marrow lineage- Sca-1+ c-Kit+ CD150+ CD48- HSPC subset (LSK
      CD150+ CD48- cells), myeloid-skewed hematopoiesis, and accrual of DNA damage in
      HSPCs. These responses were accompanied by intrinsic transcriptional alterations
      in HSPCs, including deregulation of inflammatory, survival and developmental
      pathways. Concomitant Ube2n/Ubc13 deletion from Stat3-deficient hematopoietic
      cells enabled lineage-balanced hematopoiesis, mitigated depletion of bone marrow
      LSK CD150+ CD48- cells, alleviated HSPC DNA damage, and corrected a majority of
      aberrant transcriptional responses. These results indicate an intrinsic
      protective role for STAT3 in the hematopoietic system, and suggest that this is
      mediated by STAT3-dependent restraint of excessive proinflammatory signaling via
      Ubc13 modulation.

PMID- 29463697
TI  - Membrane protein MHZ3 stabilizes OsEIN2 in rice by interacting with its Nramp
      like domain.
AB  - The phytohormone ethylene regulates many aspects of plant growth and development.
      EIN2 is the central regulator of ethylene signaling, and its turnover is crucial
      for triggering ethylene responses. Here, we identified a stabilizer of OsEIN2
      through analysis of the rice ethylene-response mutant mhz3. Loss-of-function
      mutations lead to ethylene insensitivity in etiolated rice seedlings. MHZ3
      encodes a previously uncharacterized membrane protein localized to the
      endoplasmic reticulum. Ethylene induces MHZ3 gene and protein expression.
      Genetically, MHZ3 acts at the OsEIN2 level in the signaling pathway. MHZ3
      physically interacts with OsEIN2, and both the N- and C-termini of MHZ3
      specifically associate with the OsEIN2 Nramp-like domain. Loss of mhz3 function
      reduces OsEIN2 abundance and attenuates ethylene-induced OsEIN2 accumulation,
      whereas MHZ3 overexpression elevates the abundance of both wild-type and mutated
      OsEIN2 proteins, suggesting that MHZ3 is required for proper accumulation of
      OsEIN2 protein. The association of MHZ3 with the Nramp-like domain is crucial for
      OsEIN2 accumulation, demonstrating the significance of the OsEIN2 transmembrane
      domains in ethylene signaling. Moreover, MHZ3 negatively modulates OsEIN2
      ubiquitination, protecting OsEIN2 from proteasome-mediated degradation. Together,
      these results suggest that ethylene-induced MHZ3 stabilizes OsEIN2 likely by
      binding to its Nramp-like domain and impeding protein ubiquitination to
      facilitate ethylene signal transduction. Our findings provide insight into the
      mechanisms of ethylene signaling.

PMID- 29463698
TI  - Structural basis and energy landscape for the Ca2+ gating and calmodulation of
      the Kv7.2 K+ channel.
AB  - The Kv7.2 (KCNQ2) channel is the principal molecular component of the slow
      voltage-gated, noninactivating K+ M-current, a key controller of neuronal
      excitability. To investigate the calmodulin (CaM)-mediated Ca2+ gating of the
      channel, we used NMR spectroscopy to structurally and dynamically describe the
      association of helices hA and hB of Kv7.2 with CaM, as a function of Ca2+
      concentration. The structures of the CaM/Kv7.2-hAB complex at two different
      calcification states are reported here. In the presence of a basal cytosolic Ca2+
      concentration (10-100 nM), only the N-lobe of CaM is Ca2+-loaded and the complex
      (representative of the open channel) exhibits collective dynamics on the
      millisecond time scale toward a low-populated excited state (1.5%) that
      corresponds to the inactive state of the channel. In response to a chemical or
      electrical signal, intracellular Ca2+ levels rise up to 1-10 MUM, triggering Ca2+
      association with the C-lobe. The associated conformational rearrangement is the
      key biological signal that shifts populations to the closed/inactive channel.
      This reorientation affects the C-lobe of CaM and both helices in Kv7.2,
      allosterically transducing the information from the Ca2+-binding site to the
      transmembrane region of the channel.

PMID- 29463700
TI  - Correction for Conforti et al., Faulty neuronal determination and cell
      polarization are reverted by modulating HD early phenotypes.

PMID- 29463699
TI  - Massive crossover elevation via combination of HEI10 and recq4a recq4b during
      Arabidopsis meiosis.
AB  - During meiosis, homologous chromosomes undergo reciprocal crossovers, which
      generate genetic diversity and underpin classical crop improvement. Meiotic
      recombination initiates from DNA double-strand breaks (DSBs), which are processed
      into single-stranded DNA that can invade a homologous chromosome. The resulting
      joint molecules can ultimately be resolved as crossovers. In Arabidopsis,
      competing pathways balance the repair of ~100-200 meiotic DSBs into ~10
      crossovers per meiosis, with the excess DSBs repaired as noncrossovers. To bias
      DSB repair toward crossovers, we simultaneously increased dosage of the
      procrossover E3 ligase gene HEI10 and introduced mutations in the anticrossovers
      helicase genes RECQ4A and RECQ4B As HEI10 and recq4a recq4b increase interfering
      and noninterfering crossover pathways, respectively, they combine additively to
      yield a massive meiotic recombination increase. Interestingly, we also show that
      increased HEI10 dosage increases crossover coincidence, which indicates an effect
      on interference. We also show that patterns of interhomolog polymorphism and
      heterochromatin drive recombination increases distally towards the subtelomeres
      in both HEI10 and recq4a recq4b backgrounds, while the centromeres remain
      crossover suppressed. These results provide a genetic framework for engineering
      meiotic recombination landscapes in plant genomes.

PMID- 29463702
TI  - Theory of signs and statistical approach to big data in assessing the relevance
      of clinical biomarkers of inflammation and oxidative stress.
AB  - Biomarkers are widely used not only as prognostic or diagnostic indicators, or as
      surrogate markers of disease in clinical trials, but also to formulate theories
      of pathogenesis. We identify two problems in the use of biomarkers in mechanistic
      studies. The first problem arises in the case of multifactorial diseases, where
      different combinations of multiple causes result in patient heterogeneity. The
      second problem arises when a pathogenic mediator is difficult to measure. This is
      the case of the oxidative stress (OS) theory of disease, where the causal
      components are reactive oxygen species (ROS) that have very short half-lives. In
      this case, it is usual to measure the traces left by the reaction of ROS with
      biological molecules, rather than the ROS themselves. Borrowing from the
      philosophical theories of signs, we look at the different facets of biomarkers
      and discuss their different value and meaning in multifactorial diseases and
      system medicine to inform their use in patient stratification in personalized
      medicine.

PMID- 29463701
TI  - Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to
      bone loss.
AB  - Bone deficits are frequent in HIV-1-infected patients. We report here that
      osteoclasts, the cells specialized in bone resorption, are infected by HIV-1 in
      vivo in humanized mice and ex vivo in human joint biopsies. In vitro, infection
      of human osteoclasts occurs at different stages of osteoclastogenesis via cell
      free viruses and, more efficiently, by transfer from infected T cells. HIV-1
      infection markedly enhances adhesion and osteolytic activity of human osteoclasts
      by modifying the structure and function of the sealing zone, the osteoclast
      specific bone degradation machinery. Indeed, the sealing zone is broader due to F
      actin enrichment of its basal units (i.e., the podosomes). The viral protein Nef
      is involved in all HIV-1-induced effects partly through the activation of Src, a
      regulator of podosomes and of their assembly as a sealing zone. Supporting these
      results, Nef-transgenic mice exhibit an increased osteoclast density and bone
      defects, and osteoclasts derived from these animals display high osteolytic
      activity. Altogether, our study evidences osteoclasts as host cells for HIV-1 and
      their pathological contribution to bone disorders induced by this virus, in part
      via Nef.

PMID- 29463703
TI  - Defining the sizes of airborne particles that mediate influenza transmission in
      ferrets.
AB  - Epidemics and pandemics of influenza are characterized by rapid global spread
      mediated by non-mutually exclusive transmission modes. The relative significance
      between contact, droplet, and airborne transmission is yet to be defined, a
      knowledge gap for implementing evidence-based infection control measures. We
      devised a transmission chamber that separates virus-laden particles by size and
      determined the particle sizes mediating transmission of influenza among ferrets
      through the air. Ferret-to-ferret transmission was mediated by airborne particles
      larger than 1.5 um, consistent with the quantity and size of virus-laden
      particles released by the donors. Onward transmission by donors was most
      efficient before fever onset and may continue for 5 days after inoculation.
      Multiple virus gene segments enhanced the transmissibility of a swine influenza
      virus among ferrets by increasing the release of virus-laden particles into the
      air. We provide direct experimental evidence of influenza transmission via
      droplets and fine droplet nuclei, albeit at different efficiency.

PMID- 29463704
TI  - Correction for Goncalves et al., Fenofibrate prevents skeletal muscle loss in
      mice with lung cancer.

PMID- 29463705
TI  - Controlling of glutamate release by neuregulin3 via inhibiting the assembly of
      the SNARE complex.
AB  - Neuregulin3 (NRG3) is a growth factor of the neuregulin (NRG) family and a risk
      gene of various severe mental illnesses including schizophrenia, bipolar
      disorders, and major depression. However, the physiological function of NRG3
      remains poorly understood. Here we show that loss of Nrg3 in GFAP-Nrg3f/f mice
      increased glutamatergic transmission, but had no effect on GABAergic
      transmission. These phenotypes were observed in Nex-Nrg3f/f mice, where Nrg3 was
      specifically knocked out in pyramidal neurons, indicating that Nrg3 regulates
      glutamatergic transmission by a cell-autonomous mechanism. Consequently, in the
      absence of Nrg3 in pyramidal neurons, mutant mice displayed various behavioral
      deficits related to mental illnesses. We show that the Nrg3 mutation decreased
      paired-pulse facilitation, increased decay of NMDAR currents when treated with
      MK801, and increased minimal stimulation-elicited response, providing evidence
      that the Nrg3 mutation increases glutamate release probability. Notably, Nrg3 is
      a presynaptic protein that regulates the SNARE-complex assembly. Finally,
      increased Nrg3 levels, as observed in patients with severe mental illnesses,
      suppressed glutamatergic transmission. Together, these observations indicate
      that, unlike the prototype Nrg1, the effect of which is mediated by activating
      ErbB4 in interneurons, Nrg3 is critical in controlling glutamatergic transmission
      by regulating the SNARE complex at the presynaptic terminals, identifying a
      function of Nrg3 and revealing a pathophysiological mechanism for hypofunction of
      the glutamatergic pathway in Nrg3-related severe mental illnesses.

PMID- 29463706
TI  - MotAB-like machinery drives the movement of MreB filaments during bacterial
      gliding motility.
AB  - MreB is a bacterial actin that is important for cell shape and cell wall
      biosynthesis in many bacterial species. MreB also plays crucial roles in
      Myxococcus xanthus gliding motility, but the underlying mechanism remains
      unknown. Here we tracked the dynamics of single MreB particles in M. xanthus
      using single-particle tracking photoactivated localization microscopy. We found
      that a subpopulation of MreB particles moves rapidly along helical trajectories,
      similar to the movements of the MotAB-like gliding motors. The rapid MreB motion
      was stalled in the mutants that carried truncated gliding motors. Remarkably, M.
      xanthus MreB moves one to two orders of magnitude faster than its homologs that
      move along with the cell wall synthesis machinery in Bacillus subtilis and
      Escherichia coli, and this rapid movement was not affected by the inhibitors of
      cell wall biosynthesis. Our results show that in M. xanthus, MreB provides a
      scaffold for the gliding motors while the gliding machinery drives the movement
      of MreB filaments, analogous to the interdependent movements of myosin motors and
      actin in eukaryotic cells.

PMID- 29463707
TI  - Robo and Ror function in a common receptor complex to regulate Wnt-mediated
      neurite outgrowth in Caenorhabditis elegans.
AB  - Growing axons are exposed to various guidance cues en route to their targets, but
      the mechanisms that govern the response of growth cones to combinations of
      signals remain largely elusive. Here, we found that the sole Robo receptor, SAX
      3, in Caenorhabditis elegans functions as a coreceptor for Wnt/CWN-2 molecules.
      SAX-3 binds to Wnt/CWN-2 and facilitates the membrane recruitment of CWN-2. SAX-3
      forms a complex with the Ror/CAM-1 receptor and its downstream effector Dsh/DSH
      1, promoting signal transduction from Wnt to Dsh. sax-3 functions in Wnt
      responsive cells and the SAX-3 receptor is restricted to the side of the cell
      from which the neurite is extended. DSH-1 has a similar asymmetric distribution,
      which is disrupted by sax-3 mutation. Taking these results together, we propose
      that Robo receptor can function as a Wnt coreceptor to regulate Wnt-mediated
      biological processes in vivo.

PMID- 29463708
TI  - Environmental enrichment and exercise are better than social enrichment to reduce
      memory deficits in amyloid beta neurotoxicity.
AB  - Recently, nongenetic animal models to study the onset and development of
      Alzheimer's disease (AD) have appeared, such as the intrahippocampal infusion of
      peptides present in Alzheimer amyloid plaques [i.e., amyloid-beta (Abeta)].
      Nonpharmacological approaches to AD treatment also have been advanced recently,
      which involve combinations of behavioral interventions whose specific effects are
      often difficult to determine. Here we isolate the neuroprotective effects of
      three of these interventions-environmental enrichment (EE), anaerobic physical
      exercise (AnPE), and social enrichment (SE)-on Abeta-induced oxidative stress and
      on impairments in learning and memory induced by Abeta. Wistar rats were
      submitted to 8 wk of EE, AnPE, or SE, followed by Abeta infusion in the dorsal
      hippocampus. Short-term memory (STM) and long-term memory (LTM) of object
      recognition (OR) and social recognition (SR) were evaluated. Biochemical assays
      determined hippocampal oxidative status: reactive oxygen species, lipid
      peroxidation by thiobarbituric acid reactive substance (TBARS) test, and total
      antioxidant capacity by ferric reducing/antioxidant power (FRAP), as well as
      acetylcholinesterase activity. Abeta infusion resulted in memory deficits and
      hippocampal oxidative damage. EE and AnPE prevented all memory deficits (STM and
      LTM of OR and SR) and lipid peroxidation (i.e., TBARS). SE prevented only the SR
      memory deficits and the decrease of total antioxidant capacity decrease (i.e.,
      FRAP). Traditionally, findings obtained with EE protocols do not allow
      discrimination of the roles of the three individual factors involved. Here we
      demonstrate that EE and physical exercise have better neuroprotective effects
      than SE in memory deficits related to Abeta neurotoxicity in the AD model tested.

PMID- 29463709
TI  - Identification of the YEATS domain of GAS41 as a pH-dependent reader of histone
      succinylation.
AB  - Lysine succinylation is a newly discovered posttranslational modification with
      distinctive physical properties. However, to date rarely have studies reported
      effectors capable of interpreting this modification on histones. Following our
      previous study of SIRT5 as an eraser of succinyl-lysine (Ksuc), here we
      identified the GAS41 YEATS domain as a reader of Ksuc on histones. Biochemical
      studies showed that the GAS41 YEATS domain presents significant binding affinity
      toward H3K122suc upon a protonated histidine residue. Furthermore, cellular
      studies showed that GAS41 had prominent interaction with H3K122suc on histones
      and also demonstrated the coenrichment of GAS41 and H3K122suc on the p21
      promoter. To investigate the binding mechanism, we solved the crystal structure
      of the YEATS domain of Yaf9, the GAS41 homolog, in complex with an H3K122suc
      peptide that demonstrated the presence of a salt bridge formed when a protonated
      histidine residue (His39) recognizes the carboxyl terminal of the succinyl group.
      We also solved the apo structure of GAS41 YEATS domain, in which the conserved
      His43 residue superimposes well with His39 in the Yaf9 structure. Our findings
      identified a reader of succinyl-lysine, and the binding mechanism will provide
      insight into the development of specific regulators targeting GAS41.

PMID- 29463711
TI  - Demographic compensation does not rescue populations at a trailing range edge.
AB  - Species' geographic ranges and climatic niches are likely to be increasingly
      mismatched due to rapid climate change. If a species' range and niche are out of
      equilibrium, then population performance should decrease from high-latitude
      "leading" range edges, where populations are expanding into recently ameliorated
      habitats, to low-latitude "trailing" range edges, where populations are
      contracting from newly unsuitable areas. Demographic compensation is a phenomenon
      whereby declines in some vital rates are offset by increases in others across
      time or space. In theory, demographic compensation could increase the range of
      environments over which populations can succeed and forestall range contraction
      at trailing edges. An outstanding question is whether range limits and range
      contractions reflect inadequate demographic compensation across environmental
      gradients, causing population declines at range edges. We collected demographic
      data from 32 populations of the scarlet monkeyflower (Erythranthe cardinalis)
      spanning 11 degrees  of latitude in western North America and used integral
      projection models to evaluate population dynamics and assess demographic
      compensation across the species' range. During the 5-y study period, which
      included multiple years of severe drought and warming, population growth rates
      decreased from north to south, consistent with leading-trailing dynamics.
      Southern populations at the trailing range edge declined due to reduced survival,
      growth, and recruitment, despite compensatory increases in reproduction and
      faster life-history characteristics. These results suggest that demographic
      compensation may only delay population collapse without the return of more
      favorable conditions or the contribution of other buffering mechanisms such as
      evolutionary rescue.

PMID- 29463710
TI  - Optically functional isoxanthopterin crystals in the mirrored eyes of decapod
      crustaceans.
AB  - The eyes of some aquatic animals form images through reflective optics. Shrimp,
      lobsters, crayfish, and prawns possess reflecting superposition compound eyes,
      composed of thousands of square-faceted eye units (ommatidia). Mirrors in the
      upper part of the eye (the distal mirror) reflect light collected from many
      ommatidia onto the photosensitive elements of the retina, the rhabdoms. A second
      reflector, the tapetum, underlying the retina, back-scatters dispersed light onto
      the rhabdoms. Using microCT and cryo-SEM imaging accompanied by in situ micro-X
      ray diffraction and micro-Raman spectroscopy, we investigated the hierarchical
      organization and materials properties of the reflective systems at high
      resolution and under close-to-physiological conditions. We show that the distal
      mirror consists of three or four layers of plate-like nanocrystals. The tapetum
      is a diffuse reflector composed of hollow nanoparticles constructed from
      concentric lamellae of crystals. Isoxanthopterin, a pteridine analog of guanine,
      forms both the reflectors in the distal mirror and in the tapetum. The crystal
      structure of isoxanthopterin was determined from crystal-structure prediction
      calculations and verified by comparison with experimental X-ray diffraction. The
      extended hydrogen-bonded layers of the molecules result in an extremely high
      calculated refractive index in the H-bonded plane, n = 1.96, which makes
      isoxanthopterin crystals an ideal reflecting material. The crystal structure of
      isoxanthopterin, together with a detailed knowledge of the reflector
      superstructures, provide a rationalization of the reflective optics of the
      crustacean eye.

PMID- 29463712
TI  - Fundamental limits on dynamic inference from single-cell snapshots.
AB  - Single-cell expression profiling reveals the molecular states of individual cells
      with unprecedented detail. Because these methods destroy cells in the process of
      analysis, they cannot measure how gene expression changes over time. However,
      some information on dynamics is present in the data: the continuum of molecular
      states in the population can reflect the trajectory of a typical cell. Many
      methods for extracting single-cell dynamics from population data have been
      proposed. However, all such attempts face a common limitation: for any measured
      distribution of cell states, there are multiple dynamics that could give rise to
      it, and by extension, multiple possibilities for underlying mechanisms of gene
      regulation. Here, we describe the aspects of gene expression dynamics that cannot
      be inferred from a static snapshot alone and identify assumptions necessary to
      constrain a unique solution for cell dynamics from static snapshots. We translate
      these constraints into a practical algorithmic approach, population balance
      analysis (PBA), which makes use of a method from spectral graph theory to solve a
      class of high-dimensional differential equations. We use simulations to show the
      strengths and limitations of PBA, and then apply it to single-cell profiles of
      hematopoietic progenitor cells (HPCs). Cell state predictions from this analysis
      agree with HPC fate assays reported in several papers over the past two decades.
      By highlighting the fundamental limits on dynamic inference faced by any method,
      our framework provides a rigorous basis for dynamic interpretation of a gene
      expression continuum and clarifies best experimental designs for trajectory
      reconstruction from static snapshot measurements.

PMID- 29463713
TI  - Substrate binding to BamD triggers a conformational change in BamA to control
      membrane insertion.
AB  - The beta-barrel assembly machine (Bam) complex folds and inserts integral
      membrane proteins into the outer membrane of Gram-negative bacteria. The two
      essential components of the complex, BamA and BamD, both interact with
      substrates, but how the two coordinate with each other during assembly is not
      clear. To elucidate aspects of this process we slowed the assembly of an
      essential beta-barrel substrate of the Bam complex, LptD, by changing a conserved
      residue near the C terminus. This defective substrate is recruited to the Bam
      complex via BamD but is unable to integrate into the membrane efficiently.
      Changes in the extracellular loops of BamA partially restore assembly kinetics,
      implying that BamA fails to engage this defective substrate. We conclude that
      substrate binding to BamD activates BamA by regulating extracellular loop
      interactions for folding and membrane integration.

PMID- 29463715
TI  - Correction for Leftwich et al., Gut microbiomes and reproductive isolation in
      Drosophila.

PMID- 29463714
TI  - Carbon monoxide protects the kidney through the central circadian clock and CD39.
AB  - Ischemia reperfusion injury (IRI) is the predominant tissue insult associated
      with organ transplantation. Treatment with carbon monoxide (CO) modulates the
      innate immune response associated with IRI and accelerates tissue recovery. The
      mechanism has been primarily descriptive and ascribed to the ability of CO to
      influence inflammation, cell death, and repair. In a model of bilateral kidney
      IRI in mice, we elucidate an intricate relationship between CO and purinergic
      signaling involving increased CD39 ectonucleotidase expression, decreased
      expression of Adora1, with concomitant increased expression of Adora2a/2b. This
      response is linked to a >20-fold increase in expression of the circadian rhythm
      protein Period 2 (Per2) and a fivefold increase in serum erythropoietin (EPO),
      both of which contribute to abrogation of kidney IRI. CO is ineffective against
      IRI in Cd39-/- and Per2-/- mice or in the presence of a neutralizing antibody to
      EPO. Collectively, these data elucidate a cellular signaling mechanism whereby CO
      modulates purinergic responses and circadian rhythm to protect against injury.
      Moreover, these effects involve CD39- and adenosinergic-dependent stabilization
      of Per2. As CO also increases serum EPO levels in human volunteers, these
      findings continue to support therapeutic use of CO to treat IRI in association
      with organ transplantation, stroke, and myocardial infarction.

PMID- 29463716
TI  - The timescale of early land plant evolution.
AB  - Establishing the timescale of early land plant evolution is essential for testing
      hypotheses on the coevolution of land plants and Earth's System. The sparseness
      of early land plant megafossils and stratigraphic controls on their distribution
      make the fossil record an unreliable guide, leaving only the molecular clock.
      However, the application of molecular clock methodology is challenged by the
      current impasse in attempts to resolve the evolutionary relationships among the
      living bryophytes and tracheophytes. Here, we establish a timescale for early
      land plant evolution that integrates over topological uncertainty by exploring
      the impact of competing hypotheses on bryophyte-tracheophyte relationships, among
      other variables, on divergence time estimation. We codify 37 fossil calibrations
      for Viridiplantae following best practice. We apply these calibrations in a
      Bayesian relaxed molecular clock analysis of a phylogenomic dataset encompassing
      the diversity of Embryophyta and their relatives within Viridiplantae. Topology
      and dataset sizes have little impact on age estimates, with greater differences
      among alternative clock models and calibration strategies. For all analyses, a
      Cambrian origin of Embryophyta is recovered with highest probability. The
      estimated ages for crown tracheophytes range from Late Ordovician to late
      Silurian. This timescale implies an early establishment of terrestrial ecosystems
      by land plants that is in close accord with recent estimates for the origin of
      terrestrial animal lineages. Biogeochemical models that are constrained by the
      fossil record of early land plants, or attempt to explain their impact, must
      consider the implications of a much earlier, middle Cambrian-Early Ordovician,
      origin.

PMID- 29463717
TI  - Sarcomeric perturbations of myosin motors lead to dilated cardiomyopathy in
      genetically modified MYL2 mice.
AB  - Dilated cardiomyopathy (DCM) is a devastating heart disease that affects about 1
      million people in the United States, but the underlying mechanisms remain poorly
      understood. In this study, we aimed to determine the biomechanical and structural
      causes of DCM in transgenic mice carrying a novel mutation in the MYL2 gene,
      encoding the cardiac myosin regulatory light chain. Transgenic D94A (aspartic
      acid-to-alanine) mice were created and investigated by echocardiography and
      invasive hemodynamic and molecular structural and functional assessments.
      Consistent with the DCM phenotype, a significant reduction of the ejection
      fraction (EF) was observed in ~5- and ~12-mo-old male and female D94A lines
      compared with respective WT controls. Younger male D94A mice showed a more
      pronounced left ventricular (LV) chamber dilation compared with female
      counterparts, but both sexes of D94A lines developed DCM by 12 mo of age. The
      hypocontractile activity of D94A myosin motors resulted in the rightward shift of
      the force-pCa dependence and decreased actin-activated myosin ATPase activity.
      Consistent with a decreased Ca2+ sensitivity of contractile force, a small-angle
      X-ray diffraction study, performed in D94A fibers at submaximal Ca2+
      concentrations, revealed repositioning of the D94A cross-bridge mass toward the
      thick-filament backbone supporting the hypocontractile state of D94A myosin
      motors. Our data suggest that structural perturbations at the level of sarcomeres
      result in aberrant cardiomyocyte cytoarchitecture and lead to LV chamber dilation
      and decreased EF, manifesting in systolic dysfunction of D94A hearts. The D94A
      induced development of DCM in mice closely follows the clinical phenotype and
      suggests that MYL2 may serve as a new therapeutic target for dilated
      cardiomyopathy.

PMID- 29463718
TI  - Structure of full-length human TRPM4.
AB  - Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely
      distributed, calcium-activated, monovalent-selective cation channel. Mutations in
      human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report
      the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state
      at pH 7.5 to an overall resolution of 3.7 A. Five partially hydrated sodium ions
      are proposed to occupy the center of the conduction pore and the entrance to the
      coiled-coil domain. We identify an upper gate in the selectivity filter and a
      lower gate at the entrance to the cytoplasmic coiled-coil domain. Intramolecular
      interactions exist between the TRP domain and the S4-S5 linker, N-terminal
      domain, and N and C termini. Finally, we identify aromatic interactions via pi-pi
      bonds and cation-pi bonds, glycosylation at an N-linked extracellular site, a
      pore-loop disulfide bond, and 24 lipid binding sites. We compare and contrast
      this structure with other TRP channels and discuss potential mechanisms of
      regulation and gating of human full-length TRPM4.

PMID- 29463719
TI  - STED nanoscopy of the centrosome linker reveals a CEP68-organized, periodic
      rootletin network anchored to a C-Nap1 ring at centrioles.
AB  - The centrosome linker proteins C-Nap1, rootletin, and CEP68 connect the two
      centrosomes of a cell during interphase into one microtubule-organizing center.
      This coupling is important for cell migration, cilia formation, and timing of
      mitotic spindle formation. Very little is known about the structure of the
      centrosome linker. Here, we used stimulated emission depletion (STED) microscopy
      to show that each C-Nap1 ring at the proximal end of the two centrioles organizes
      a rootletin ring and, in addition, multiple rootletin/CEP68 fibers.
      Rootletin/CEP68 fibers originating from the two centrosomes form a web-like,
      interdigitating network, explaining the flexible nature of the centrosome linker.
      The rootletin/CEP68 filaments are repetitive and highly ordered. Staggered
      rootletin molecules (N-to-N and C-to-C) within the filaments are 75 nm apart.
      Rootletin binds CEP68 via its C-terminal spectrin repeat-containing region in 75
      nm intervals. The N-to-C distance of two rootletin molecules is ~35 to 40 nm,
      leading to an estimated minimal rootletin length of ~110 nm. CEP68 is important
      in forming rootletin filaments that branch off centrioles and to modulate the
      thickness of rootletin fibers. Thus, the centrosome linker consists of a vast
      network of repeating rootletin units with C-Nap1 as ring organizer and CEP68 as
      filament modulator.

PMID- 29463721
TI  - Fast flow-based algorithm for creating density-equalizing map projections.
AB  - Cartograms are maps that rescale geographic regions (e.g., countries, districts)
      such that their areas are proportional to quantitative demographic data (e.g.,
      population size, gross domestic product). Unlike conventional bar or pie charts,
      cartograms can represent correctly which regions share common borders, resulting
      in insightful visualizations that can be the basis for further spatial
      statistical analysis. Computer programs can assist data scientists in preparing
      cartograms, but developing an algorithm that can quickly transform every
      coordinate on the map (including points that are not exactly on a border) while
      generating recognizable images has remained a challenge. Methods that translate
      the cartographic deformations into physics-inspired equations of motion have
      become popular, but solving these equations with sufficient accuracy can still
      take several minutes on current hardware. Here we introduce a flow-based
      algorithm whose equations of motion are numerically easier to solve compared with
      previous methods. The equations allow straightforward parallelization so that the
      calculation takes only a few seconds even for complex and detailed input. Despite
      the speedup, the proposed algorithm still keeps the advantages of previous
      techniques: With comparable quantitative measures of shape distortion, it
      accurately scales all areas, correctly fits the regions together, and generates a
      map projection for every point. We demonstrate the use of our algorithm with
      applications to the 2016 US election results, the gross domestic products of
      Indian states and Chinese provinces, and the spatial distribution of deaths in
      the London borough of Kensington and Chelsea between 2011 and 2014.

PMID- 29463720
TI  - Gi- and Gs-coupled GPCRs show different modes of G-protein binding.
AB  - More than two decades ago, the activation mechanism for the membrane-bound
      photoreceptor and prototypical G protein-coupled receptor (GPCR) rhodopsin was
      uncovered. Upon light-induced changes in ligand-receptor interaction, movement of
      specific transmembrane helices within the receptor opens a crevice at the
      cytoplasmic surface, allowing for coupling of heterotrimeric guanine nucleotide
      binding proteins (G proteins). The general features of this activation mechanism
      are conserved across the GPCR superfamily. Nevertheless, GPCRs have selectivity
      for distinct G-protein family members, but the mechanism of selectivity remains
      elusive. Structures of GPCRs in complex with the stimulatory G protein, Gs, and
      an accessory nanobody to stabilize the complex have been reported, providing
      information on the intermolecular interactions. However, to reveal the structural
      selectivity filters, it will be necessary to determine GPCR-G protein structures
      involving other G-protein subtypes. In addition, it is important to obtain
      structures in the absence of a nanobody that may influence the structure. Here,
      we present a model for a rhodopsin-G protein complex derived from intermolecular
      distance constraints between the activated receptor and the inhibitory G protein,
      Gi, using electron paramagnetic resonance spectroscopy and spin-labeling
      methodologies. Molecular dynamics simulations demonstrated the overall stability
      of the modeled complex. In the rhodopsin-Gi complex, Gi engages rhodopsin in a
      manner distinct from previous GPCR-Gs structures, providing insight into
      specificity determinants.

PMID- 29463723
TI  - Rainfall statistics, stationarity, and climate change.
AB  - There is a growing research interest in the detection of changes in hydrologic
      and climatic time series. Stationarity can be assessed using the autocorrelation
      function, but this is not yet common practice in hydrology and climate. Here, we
      use a global land-based gridded annual precipitation (hereafter P) database (1940
      2009) and find that the lag 1 autocorrelation coefficient is statistically
      significant at around 14% of the global land surface, implying nonstationary
      behavior (90% confidence). In contrast, around 76% of the global land surface
      shows little or no change, implying stationary behavior. We use these results to
      assess change in the observed P over the most recent decade of the database. We
      find that the changes for most (84%) grid boxes are within the plausible bounds
      of no significant change at the 90% CI. The results emphasize the importance of
      adequately accounting for natural variability when assessing change.

PMID- 29463722
TI  - Tracking the route of molecular oxygen in O2-tolerant membrane-bound [NiFe]
      hydrogenase.
AB  - [NiFe] hydrogenases catalyze the reversible splitting of H2 into protons and
      electrons at a deeply buried active site. The catalytic center can be accessed by
      gas molecules through a hydrophobic tunnel network. While most [NiFe]
      hydrogenases are inactivated by O2, a small subgroup, including the membrane
      bound [NiFe] hydrogenase (MBH) of Ralstonia eutropha, is able to overcome aerobic
      inactivation by catalytic reduction of O2 to water. This O2 tolerance relies on a
      special [4Fe3S] cluster that is capable of releasing two electrons upon O2
      attack. Here, the O2 accessibility of the MBH gas tunnel network has been probed
      experimentally using a "soak-and-freeze" derivatization method, accompanied by
      protein X-ray crystallography and computational studies. This combined approach
      revealed several sites of O2 molecules within a hydrophobic tunnel network
      leading, via two tunnel entrances, to the catalytic center of MBH. The
      corresponding site occupancies were related to the O2 concentrations used for MBH
      crystal derivatization. The examination of the O2-derivatized data furthermore
      uncovered two unexpected structural alterations at the [4Fe3S] cluster, which
      might be related to the O2 tolerance of the enzyme.

PMID- 29463724
TI  - Distinct sets of tethering complexes, SNARE complexes, and Rab GTPases mediate
      membrane fusion at the vacuole in Arabidopsis.
AB  - Membrane trafficking plays pivotal roles in various cellular activities and
      higher-order functions of eukaryotes and requires tethering factors to mediate
      contact between transport intermediates and target membranes. Two evolutionarily
      conserved tethering complexes, homotypic fusion and protein sorting (HOPS) and
      class C core vacuole/endosome tethering (CORVET), are known to act in
      endosomal/vacuolar transport in yeast and animals. Both complexes share a core
      subcomplex consisting of Vps11, Vps18, Vps16, and Vps33, and in addition to this
      core, HOPS contains Vps39 and Vps41, whereas CORVET contains Vps3 and Vps8. HOPS
      and CORVET subunits are also conserved in the model plant Arabidopsis. However,
      vacuolar trafficking in plants occurs through multiple unique transport pathways,
      and how these conserved tethering complexes mediate endosomal/vacuolar transport
      in plants has remained elusive. In this study, we investigated the functions of
      VPS18, VPS3, and VPS39, which are core complex, CORVET-specific, and HOPS
      specific subunits, respectively. Impairment of these tethering proteins resulted
      in embryonic lethality, distinctly altering vacuolar morphology and perturbing
      transport of a vacuolar membrane protein. CORVET interacted with canonical RAB5
      and a plant-specific R-soluble NSF attachment protein receptor (SNARE), VAMP727,
      which mediates fusion between endosomes and the vacuole, whereas HOPS interacted
      with RAB7 and another R-SNARE, VAMP713, which likely mediates homotypic vacuolar
      fusion. These results indicate that CORVET and HOPS act in distinct vacuolar
      trafficking pathways in plant cells, unlike those of nonplant systems that
      involve sequential action of these tethering complexes during vacuolar/lysosomal
      trafficking. These results highlight a unique diversification of
      vacuolar/lysosomal transport that arose during plant evolution, using
      evolutionarily conserved tethering components.

PMID- 29463725
TI  - Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory
      precursors, and is dispensable for T cell exhaustion.
AB  - Tim-3 is highly expressed on a subset of T cells during T cell exhaustion in
      settings of chronic viral infection and tumors. Using lymphocytic
      choriomeningitis virus (LCMV) Clone 13, a model for chronic infection, we found
      that Tim-3 was neither necessary nor sufficient for the development of T cell
      exhaustion. Nonetheless, expression of Tim-3 was sufficient to drive resistance
      to PD-L1 blockade therapy during chronic infection. Strikingly, expression of Tim
      3 promoted the development of short-lived effector T cells, at the expense of
      memory precursor development, after acute LCMV infection. These effects were
      accompanied by increased Akt/mTOR signaling in T cells expressing endogenous or
      ectopic Tim-3. Conversely, Akt/mTOR signaling was reduced in effector T cells
      from Tim-3-deficient mice. Thus, Tim-3 is essential for optimal effector T cell
      responses, and may also contribute to exhaustion by restricting the development
      of long-lived memory T cells. Taken together, our results suggest that Tim-3 is
      actually more similar to costimulatory receptors that are up-regulated after T
      cell activation than to a dominant inhibitory protein like PD-1. These findings
      have significant implications for the development of anti-Tim-3 antibodies as
      therapeutic agents.

PMID- 29463726
TI  - Structures of the prefusion form of measles virus fusion protein in complex with
      inhibitors.
AB  - Measles virus (MeV), a major cause of childhood morbidity and mortality, is
      highly immunotropic and one of the most contagious pathogens. MeV may establish,
      albeit rarely, persistent infection in the central nervous system, causing fatal
      and intractable neurodegenerative diseases such as subacute sclerosing
      panencephalitis and measles inclusion body encephalitis. Recent studies have
      suggested that particular substitutions in the MeV fusion (F) protein are
      involved in the pathogenesis by destabilizing the F protein and endowing it with
      hyperfusogenicity. Here we show the crystal structures of the prefusion MeV-F
      alone and in complex with the small compound AS-48 or a fusion inhibitor peptide.
      Notably, these independently developed inhibitors bind the same hydrophobic
      pocket located at the region connecting the head and stalk of MeV-F, where a
      number of substitutions in MeV isolates from neurodegenerative diseases are also
      localized. Since these inhibitors could suppress membrane fusion mediated by most
      of the hyperfusogenic MeV-F mutants, the development of more effective inhibitors
      based on the structures may be warranted to treat MeV-induced neurodegenerative
      diseases.

PMID- 29463728
TI  - Correction for Woelders et al., Melanopsin- and L-cone-induced pupil constriction
      is inhibited by S- and M-cones in humans.

PMID- 29463727
TI  - The secreted metabolome of Streptomyces chartreusis and implications for
      bacterial chemistry.
AB  - Actinomycetes are known for producing diverse secondary metabolites. Combining
      genomics with untargeted data-dependent tandem MS and molecular networking, we
      characterized the secreted metabolome of the tunicamycin producer Streptomyces
      chartreusis NRRL 3882. The genome harbors 128 predicted biosynthetic gene
      clusters. We detected >1,000 distinct secreted metabolites in culture
      supernatants, only 22 of which were identified based on standards and public
      spectral libraries. S. chartreusis adapts the secreted metabolome to cultivation
      conditions. A number of metabolites are produced iron dependently, among them 17
      desferrioxamine siderophores aiding in iron acquisition. Eight previously unknown
      members of this long-known compound class are described. A single desferrioxamine
      synthesis gene cluster was detected in the genome, yet different sets of
      desferrioxamines are produced in different media. Additionally, a polyether
      ionophore, differentially produced by the calcimycin biosynthesis cluster, was
      discovered. This illustrates that metabolite output of a single biosynthetic
      machine can be exquisitely regulated not only with regard to product quantity but
      also with regard to product range. Compared with chemically defined medium, in
      complex medium, total metabolite abundance was higher, structural diversity
      greater, and the average molecular weight almost doubled. Tunicamycins, for
      example, were only produced in complex medium. Extrapolating from this study, we
      anticipate that the larger part of bacterial chemistry, including chemical
      structures, ecological functions, and pharmacological potential, is yet to be
      uncovered.

PMID- 29463729
TI  - NLR surveillance of essential SEC-9 SNARE proteins induces programmed cell death
      upon allorecognition in filamentous fungi.
AB  - In plants and metazoans, intracellular receptors that belong to the NOD-like
      receptor (NLR) family are major contributors to innate immunity. Filamentous
      fungal genomes contain large repertoires of genes encoding for proteins with
      similar architecture to plant and animal NLRs with mostly unknown function. Here,
      we identify and molecularly characterize patatin-like phospholipase-1 (PLP-1), an
      NLR-like protein containing an N-terminal patatin-like phospholipase domain, a
      nucleotide-binding domain (NBD), and a C-terminal tetratricopeptide repeat (TPR)
      domain. PLP-1 guards the essential SNARE protein SEC-9; genetic differences at
      plp-1 and sec-9 function to trigger allorecognition and cell death in two
      distantly related fungal species, Neurospora crassa and Podospora anserina
      Analyses of Neurospora population samples revealed that plp-1 and sec-9 alleles
      are highly polymorphic, segregate into discrete haplotypes, and show transspecies
      polymorphism. Upon fusion between cells bearing incompatible sec-9 and plp-1
      alleles, allorecognition and cell death are induced, which are dependent upon
      physical interaction between SEC-9 and PLP-1. The central NBD and patatin-like
      phospholipase activity of PLP-1 are essential for allorecognition and cell death,
      while the TPR domain and the polymorphic SNARE domain of SEC-9 function in
      conferring allelic specificity. Our data indicate that fungal NLR-like proteins
      function similar to NLR immune receptors in plants and animals, showing that NLRs
      are major contributors to innate immunity in plants and animals and for
      allorecognition in fungi.

PMID- 29463730
TI  - Long-term potentiation expands information content of hippocampal dentate gyrus
      synapses.
AB  - An approach combining signal detection theory and precise 3D reconstructions from
      serial section electron microscopy (3DEM) was used to investigate synaptic
      plasticity and information storage capacity at medial perforant path synapses in
      adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation
      (LTP) markedly increased the frequencies of both small and large spines measured
      30 minutes later. This bidirectional expansion resulted in heterosynaptic
      counterbalancing of total synaptic area per unit length of granule cell dendrite.
      Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage
      capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast,
      control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic
      precision than either control or potentiated dentate gyrus synapses. Thus,
      synaptic plasticity altered total capacity, yet hippocampal subregions differed
      dramatically in their synaptic information storage capacity, reflecting their
      diverse functions and activation histories.

PMID- 29463731
TI  - Gibberellin DELLA signaling targets the retromer complex to redirect protein
      trafficking to the plasma membrane.
AB  - The plant hormone gibberellic acid (GA) is a crucial regulator of growth and
      development. The main paradigm of GA signaling puts forward transcriptional
      regulation via the degradation of DELLA transcriptional repressors. GA has also
      been shown to regulate tropic responses by modulation of the plasma membrane
      incidence of PIN auxin transporters by an unclear mechanism. Here we uncovered
      the cellular and molecular mechanisms by which GA redirects protein trafficking
      and thus regulates cell surface functionality. Photoconvertible reporters
      revealed that GA balances the protein traffic between the vacuole degradation
      route and recycling back to the cell surface. Low GA levels promote vacuolar
      delivery and degradation of multiple cargos, including PIN proteins, whereas high
      GA levels promote their recycling to the plasma membrane. This GA effect requires
      components of the retromer complex, such as Sorting Nexin 1 (SNX1) and its
      interacting, microtubule (MT)-associated protein, the Cytoplasmic Linker
      Associated Protein (CLASP1). Accordingly, GA regulates the subcellular
      distribution of SNX1 and CLASP1, and the intact MT cytoskeleton is essential for
      the GA effect on trafficking. This GA cellular action occurs through DELLA
      proteins that regulate the MT and retromer presumably via their interaction
      partners Prefoldins (PFDs). Our study identified a branching of the GA signaling
      pathway at the level of DELLA proteins, which, in parallel to regulating
      transcription, also target by a nontranscriptional mechanism the retromer complex
      acting at the intersection of the degradation and recycling trafficking routes.
      By this mechanism, GA can redirect receptors and transporters to the cell
      surface, thus coregulating multiple processes, including PIN-dependent auxin
      fluxes during tropic responses.

PMID- 29463732
TI  - Diet-induced mating preference in Drosophila.

PMID- 29463733
TI  - Reply to Rosenberg et al.: Diet, gut bacteria, and assortative mating in
      Drosophila melanogaster.

PMID- 29463734
TI  - Reply to Huszar: The elastic weight consolidation penalty is empirically valid.

PMID- 29463735
TI  - Note on the quadratic penalties in elastic weight consolidation.

PMID- 29463736
TI  - OligoMiner provides a rapid, flexible environment for the design of genome-scale
      oligonucleotide in situ hybridization probes.
AB  - Oligonucleotide (oligo)-based FISH has emerged as an important tool for the study
      of chromosome organization and gene expression and has been empowered by the
      commercial availability of highly complex pools of oligos. However, a dedicated
      bioinformatic design utility has yet to be created specifically for the purpose
      of identifying optimal oligo FISH probe sequences on the genome-wide scale. Here,
      we introduce OligoMiner, a rapid and robust computational pipeline for the genome
      scale design of oligo FISH probes that affords the scientist exact control over
      the parameters of each probe. Our streamlined method uses standard bioinformatic
      file formats, allowing users to seamlessly integrate new and existing utilities
      into the pipeline as desired, and introduces a method for evaluating the
      specificity of each probe molecule that connects simulated hybridization
      energetics to rapidly generated sequence alignments using supervised machine
      learning. We demonstrate the scalability of our approach by performing genome
      scale probe discovery in numerous model organism genomes and showcase the
      performance of the resulting probes with diffraction-limited and single-molecule
      superresolution imaging of chromosomal and RNA targets. We anticipate that this
      pipeline will make the FISH probe design process much more accessible and will
      more broadly facilitate the design of pools of hybridization probes for a variety
      of applications.

PMID- 29463737
TI  - Pulmonary alveolar type I cell population consists of two distinct subtypes that
      differ in cell fate.
AB  - Pulmonary alveolar type I (AT1) cells cover more than 95% of alveolar surface and
      are essential for the air-blood barrier function of lungs. AT1 cells have been
      shown to retain developmental plasticity during alveolar regeneration. However,
      the development and heterogeneity of AT1 cells remain largely unknown. Here, we
      conducted a single-cell RNA-seq analysis to characterize postnatal AT1 cell
      development and identified insulin-like growth factor-binding protein 2 (Igfbp2)
      as a genetic marker specifically expressed in postnatal AT1 cells. The portion of
      AT1 cells expressing Igfbp2 increases during alveologenesis and in post
      pneumonectomy (PNX) newly formed alveoli. We found that the adult AT1 cell
      population contains both Hopx+Igfbp2+ and Hopx+Igfbp2- AT1 cells, which have
      distinct cell fates during alveolar regeneration. Using an Igfbp2-CreER mouse
      model, we demonstrate that Hopx+Igfbp2+ AT1 cells represent terminally
      differentiated AT1 cells that are not able to transdifferentiate into AT2 cells
      during post-PNX alveolar regeneration. Our study provides tools and insights that
      will guide future investigations into the molecular and cellular mechanism or
      mechanisms underlying AT1 cell fate during lung development and regeneration.

PMID- 29463738
TI  - Algorithms in the historical emergence of word senses.
AB  - Human language relies on a finite lexicon to express a potentially infinite set
      of ideas. A key result of this tension is that words acquire novel senses over
      time. However, the cognitive processes that underlie the historical emergence of
      new word senses are poorly understood. Here, we present a computational framework
      that formalizes competing views of how new senses of a word might emerge by
      attaching to existing senses of the word. We test the ability of the models to
      predict the temporal order in which the senses of individual words have emerged,
      using an historical lexicon of English spanning the past millennium. Our findings
      suggest that word senses emerge in predictable ways, following an historical path
      that reflects cognitive efficiency, predominantly through a process of nearest
      neighbor chaining. Our work contributes a formal account of the generative
      processes that underlie lexical evolution.

PMID- 29463740
TI  - Correction for Kleist et al., Chronic anthropogenic noise disrupts glucocorticoid
      signaling and has multiple effects on fitness in an avian community.

PMID- 29463739
TI  - Synthetic addiction extends the productive life time of engineered Escherichia
      coli populations.
AB  - Bio-production of chemicals is an important driver of the societal transition
      toward sustainability. However, fermentations with heavily engineered production
      organisms can be challenging to scale to industrial volumes. Such fermentations
      are subject to evolutionary pressures that select for a wide range of genetic
      variants that disrupt the biosynthetic capacity of the engineered organism.
      Synthetic product addiction that couples high-yield production of a desired
      metabolite to expression of nonconditionally essential genes could offer a
      solution to this problem by selectively favoring cells with biosynthetic capacity
      in the population without constraining the medium. We constructed such synthetic
      product addiction by controlling the expression of two nonconditionally essential
      genes with a mevalonic acid biosensor. The product-addicted production organism
      retained high-yield mevalonic acid production through 95 generations of
      cultivation, corresponding to the number of cell generations required for >200-m3
      industrial-scale production, at which time the nonaddicted strain completely
      abolished production. Using deep DNA sequencing, we find that the product
      addicted populations do not accumulate genetic variants that compromise
      biosynthetic capacity, highlighting how synthetic networks can be designed to
      control genetic population heterogeneity. Such synthetic redesign of evolutionary
      forces with endogenous processes may be a promising concept for realizing complex
      cellular designs required for sustainable bio-manufacturing.

PMID- 29463741
TI  - Transcriptional factor ICER promotes glutaminolysis and the generation of Th17
      cells.
AB  - Glutaminolysis is a well-known source of energy for effector T cells but its
      contribution to each T cell subset and the mechanisms which are responsible for
      the control of involved metabolic enzymes are not fully understood. We report
      that Th17 but not Th1, Th2, or Treg cell induction in vitro depends on
      glutaminolysis and the up-regulation of glutaminase 1 (Gls1), the first enzyme in
      the glutaminolysis pathway. Both pharmacological and siRNA-based selective
      inhibition of Gls1 reduced in vitro Th17 differentiation and reduced the CD3/TCR
      mediated increase of the mammalian target of rapamycin complex 1 activity.
      Treatment of mice with a Gls1 inhibitor ameliorated experimental autoimmune
      encephalomyelitis. Furthermore, RAG1-deficient mice that received Gls1-shRNA
      transfected 2D2 T cells had reduced experimental autoimmune encephalomyelitis
      scores compared with those that received control-shRNA-treated cells. Next we
      found that T cells deficient in inducible cAMP early repressor (ICER), a
      transcriptional factor known to promote Th17 differentiation, display reduced
      activity of oxidative phosphorylation rates in the presence of glutamine and
      reduced Gls1 expression, both of which could be restored by ICER overexpression.
      Finally, we demonstrate that ICER binds to the gls1 promoter directly and
      increases its activity. These findings demonstrate the importance of
      glutaminolysis in the generation of Th17 and the direct control of Gls1 activity
      by the IL-17-promoting transcription factor ICER. Pharmaceutical modulation of
      the glutaminolysis pathway should be considered to control Th17-mediated
      pathology.

PMID- 29463742
TI  - Origins and genetic legacies of the Caribbean Taino.
AB  - The Caribbean was one of the last parts of the Americas to be settled by humans,
      but how and when the islands were first occupied remains a matter of debate.
      Ancient DNA can help answering these questions, but the work has been hampered by
      poor DNA preservation. We report the genome sequence of a 1,000-year-old Lucayan
      Taino individual recovered from the site of Preacher's Cave in the Bahamas. We
      sequenced her genome to 12.4-fold coverage and show that she is genetically most
      closely related to present-day Arawakan speakers from northern South America,
      suggesting that the ancestors of the Lucayans originated there. Further, we find
      no evidence for recent inbreeding or isolation in the ancient genome, suggesting
      that the Lucayans had a relatively large effective population size. Finally, we
      show that the native American components in some present-day Caribbean genomes
      are closely related to the ancient Taino, demonstrating an element of continuity
      between precontact populations and present-day Latino populations in the
      Caribbean.

PMID- 29463743
TI  - In vivo repressed genes of Vibrio cholerae reveal inverse requirements of an
      H+/Cl- transporter along the gastrointestinal passage.
AB  - The facultative human pathogen Vibrio cholerae changes its transcriptional
      profile upon oral ingestion by the host to facilitate survival and colonization
      fitness. Here, we used a modified version of recombination-based in vivo
      expression technology to investigate gene silencing during the in vivo passage,
      which has been understudied. Using a murine model of cholera, we screened a V.
      cholerae transposon library composed of 10,000 randomly generated reporter
      fusions and identified 101 in vivo repressed (ivr) genes. Our data indicate that
      constitutive expression of ivr genes reduces colonization fitness, highlighting
      the necessity to down-regulate these genes in vivo. For example, the ivr gene
      clcA, encoding an H+/Cl- transporter, could be linked to the acid tolerance
      response against hydrochloric acid. In a chloride-dependent manner, ClcA
      facilitates survival under low pH (e.g., the stomach), but its presence becomes
      detrimental under alkaline conditions (e.g., lower gastrointestinal tract). This
      pH-dependent clcA expression is controlled by the LysR-type activator AphB, which
      acts in concert with AphA to initiate the virulence cascade in V. cholerae after
      oral ingestion. Thus, transcriptional networks dictating induction of virulence
      factors and the repression of ivr genes overlap to regulate in vivo colonization
      dynamics. Overall, the results presented herein highlight the impact of
      spatiotemporal gene silencing in vivo. The molecular characterization of the
      underlying mechanisms can provide important insights into in vivo physiology and
      virulence network regulation.

PMID- 29463744
TI  - MHC-mismatched mixed chimerism restores peripheral tolerance of noncross-reactive
      autoreactive T cells in NOD mice.
AB  - Autoimmune type 1 diabetes (T1D) and other autoimmune diseases are associated
      with particular MHC haplotypes and expansion of autoreactive T cells. Induction
      of MHC-mismatched but not -matched mixed chimerism by hematopoietic cell
      transplantation effectively reverses autoimmunity in diabetic nonobese diabetic
      (NOD) mice, even those with established diabetes. As expected, MHC-mismatched
      mixed chimerism mediates deletion in the thymus of host-type autoreactive T cells
      that have T-cell receptor (TCR) recognizing (cross-reacting with) donor-type
      antigen presenting cells (APCs), which have come to reside in the thymus.
      However, how MHC-mismatched mixed chimerism tolerizes host autoreactive T cells
      that recognize only self-MHC-peptide complexes remains unknown. Here, using
      NOD.Rag1-/-BDC2.5 or NOD.Rag1-/-BDC12-4.1 mice that have only noncross-reactive
      transgenic autoreactive T cells, we show that induction of MHC-mismatched but not
      -matched mixed chimerism restores immune tolerance of peripheral noncross
      reactive autoreactive T cells. MHC-mismatched mixed chimerism results in
      increased percentages of both donor- and host-type Foxp3+ Treg cells and up
      regulated expression of programmed death-ligand 1 (PD-L1) by host-type
      plasmacytoid dendritic cells (pDCs). Furthermore, adoptive transfer experiments
      showed that engraftment of donor-type dendritic cells (DCs) and expansion of
      donor-type Treg cells are required for tolerizing the noncross-reactive
      autoreactive T cells in the periphery, which are in association with up
      regulation of host-type DC expression of PD-L1 and increased percentage of host
      type Treg cells. Thus, induction of MHC-mismatched mixed chimerism may establish
      a peripheral tolerogenic DC and Treg network that actively tolerizes autoreactive
      T cells, even those with no TCR recognition of the donor APCs.

PMID- 29463746
TI  - Ants avoid superinfections by performing risk-adjusted sanitary care.
AB  - Being cared for when sick is a benefit of sociality that can reduce disease and
      improve survival of group members. However, individuals providing care risk
      contracting infectious diseases themselves. If they contract a low pathogen dose,
      they may develop low-level infections that do not cause disease but still affect
      host immunity by either decreasing or increasing the host's vulnerability to
      subsequent infections. Caring for contagious individuals can thus significantly
      alter the future disease susceptibility of caregivers. Using ants and their
      fungal pathogens as a model system, we tested if the altered disease
      susceptibility of experienced caregivers, in turn, affects their expression of
      sanitary care behavior. We found that low-level infections contracted during
      sanitary care had protective or neutral effects on secondary exposure to the same
      (homologous) pathogen but consistently caused high mortality on superinfection
      with a different (heterologous) pathogen. In response to this risk, the ants
      selectively adjusted the expression of their sanitary care. Specifically, the
      ants performed less grooming and more antimicrobial disinfection when caring for
      nestmates contaminated with heterologous pathogens compared with homologous ones.
      By modulating the components of sanitary care in this way the ants acquired less
      infectious particles of the heterologous pathogens, resulting in reduced
      superinfection. The performance of risk-adjusted sanitary care reveals the
      remarkable capacity of ants to react to changes in their disease susceptibility,
      according to their own infection history and to flexibly adjust collective care
      to individual risk.

PMID- 29463745
TI  - Rocaglates as dual-targeting agents for experimental cerebral malaria.
AB  - Cerebral malaria (CM) is a severe and rapidly progressing complication of
      infection by Plasmodium parasites that is associated with high rates of mortality
      and morbidity. Treatment options are currently few, and intervention with
      artemisinin (Art) has limited efficacy, a problem that is compounded by the
      emergence of resistance to Art in Plasmodium parasites. Rocaglates are a class of
      natural products derived from plants of the Aglaia genus that have been shown to
      interfere with eukaryotic initiation factor 4A (eIF4A), ultimately blocking
      initiation of protein synthesis. Here, we show that the rocaglate CR-1-31B
      perturbs association of Plasmodium falciparum eIF4A (PfeIF4A) with RNA. CR-1-31B
      shows potent prophylactic and therapeutic antiplasmodial activity in vivo in
      mouse models of infection with Plasmodium berghei (CM) and Plasmodium chabaudi
      (blood-stage malaria), and can also block replication of different clinical
      isolates of P. falciparum in human erythrocytes infected ex vivo, including drug
      resistant P. falciparum isolates. In vivo, a single dosing of CR-1-31B in P.
      berghei-infected animals is sufficient to provide protection against lethality.
      CR-1-31B is shown to dampen expression of the early proinflammatory response in
      myeloid cells in vitro and dampens the inflammatory response in vivo in P.
      berghei-infected mice. The dual activity of CR-1-31B as an antiplasmodial and as
      an inhibitor of the inflammatory response in myeloid cells should prove extremely
      valuable for therapeutic intervention in human cases of CM.

PMID- 29463747
TI  - Unexpected transformation of dissolved phenols to toxic dicarbonyls by hydroxyl
      radicals and UV light.
AB  - Water treatment systems frequently use strong oxidants or UV light to degrade
      chemicals that pose human health risks. Unfortunately, these treatments can
      result in the unintended transformation of organic contaminants into toxic
      products. We report an unexpected reaction through which exposure of phenolic
      compounds to hydroxyl radicals (*OH) or UV light results in the formation of
      toxic alpha,beta-unsaturated enedials and oxoenals. We show that these
      transformation products damage proteins by reacting with lysine and cysteine
      moieties. We demonstrate that phenolic compounds react with *OH produced by the
      increasingly popular UV/hydrogen peroxide (H2O2) water treatment process or UV
      light to form toxic enedials and oxoenals. In addition to raising concerns about
      potential health risks of oxidative water treatment, our findings suggest the
      potential for formation of these toxic compounds in sunlit surface waters,
      atmospheric water, and living cells. For the latter, our findings may be
      particularly relevant to efforts to understand cellular damage caused by in vivo
      production of reactive oxygen species. In particular, we demonstrate that
      exposure of the amino acid tyrosine to *OH yields an electrophilic enedial
      product that undergoes cross-linking reaction with both lysine and cysteine
      residues.

PMID- 29463748
TI  - Three-dimensional virtual histology enabled through cytoplasm-specific X-ray
      stain for microscopic and nanoscopic computed tomography.
AB  - Many histological methods require staining of the cytoplasm, which provides
      instrumental details for diagnosis. One major limitation is the production of 2D
      images obtained by destructive preparation of 3D tissue samples. X-ray absorption
      micro- and nanocomputed tomography (microCT and nanoCT) allows for a
      nondestructive investigation of a 3D tissue sample, and thus aids to determine
      regions of interest for further histological examinations. However, application
      of microCT and nanoCT to biological samples (e.g., biopsies) is limited by the
      missing contrast within soft tissue, which is important to visualize
      morphological details. We describe an eosin-based preparation overcoming the
      challenges of contrast enhancement and selectivity for certain tissues. The eosin
      based staining protocol is suitable for whole-organ staining, which then enables
      high-resolution microCT imaging of whole organs and nanoCT imaging of smaller
      tissue pieces retrieved from the original sample. Our results demonstrate
      suitability of the eosin-based staining method for diagnostic screening of 3D
      tissue samples without impeding further diagnostics through histological methods.

PMID- 29463749
TI  - Metabolic division of labor in microbial systems.
AB  - Metabolic pathways are often engineered in single microbial populations. However,
      the introduction of heterologous circuits into the host can create a substantial
      metabolic burden that limits the overall productivity of the system. This
      limitation could be overcome by metabolic division of labor (DOL), whereby
      distinct populations perform different steps in a metabolic pathway, reducing the
      burden each population will experience. While conceptually appealing, the
      conditions when DOL is advantageous have not been rigorously established. Here,
      we have analyzed 24 common architectures of metabolic pathways in which DOL can
      be implemented. Our analysis reveals general criteria defining the conditions
      that favor DOL, accounting for the burden or benefit of the pathway activity on
      the host populations as well as the transport and turnover of enzymes and
      intermediate metabolites. These criteria can help guide engineering of metabolic
      pathways and have implications for understanding evolution of natural microbial
      communities.

PMID- 29463751
TI  - Within- and across-trial dynamics of human EEG reveal cooperative interplay
      between reinforcement learning and working memory.
AB  - Learning from rewards and punishments is essential to survival and facilitates
      flexible human behavior. It is widely appreciated that multiple cognitive and
      reinforcement learning systems contribute to decision-making, but the nature of
      their interactions is elusive. Here, we leverage methods for extracting trial-by
      trial indices of reinforcement learning (RL) and working memory (WM) in human
      electro-encephalography to reveal single-trial computations beyond that afforded
      by behavior alone. Neural dynamics confirmed that increases in neural expectation
      were predictive of reduced neural surprise in the following feedback period,
      supporting central tenets of RL models. Within- and cross-trial dynamics revealed
      a cooperative interplay between systems for learning, in which WM contributes
      expectations to guide RL, despite competition between systems during choice.
      Together, these results provide a deeper understanding of how multiple neural
      systems interact for learning and decision-making and facilitate analysis of
      their disruption in clinical populations.

PMID- 29463752
TI  - Variational structure of Luttinger-Ward formalism and bold diagrammatic expansion
      for Euclidean lattice field theory.
AB  - The Luttinger-Ward functional was proposed more than five decades ago and has
      been used to formally justify most practically used Green's function methods for
      quantum many-body systems. Nonetheless, the very existence of the Luttinger-Ward
      functional has been challenged by recent theoretical and numerical evidence. We
      provide a rigorously justified Luttinger-Ward formalism, in the context of
      Euclidean lattice field theory. Using the Luttinger-Ward functional, the free
      energy can be variationally minimized with respect to Green's functions in its
      domain. We then derive the widely used bold diagrammatic expansion rigorously,
      without relying on formal arguments such as partial resummation of bare diagrams
      to infinite order.

PMID- 29463750
TI  - Light-activated protein interaction with high spatial subcellular confinement.
AB  - Methods to acutely manipulate protein interactions at the subcellular level are
      powerful tools in cell biology. Several blue-light-dependent optical dimerization
      tools have been developed. In these systems one protein component of the dimer
      (the bait) is directed to a specific subcellular location, while the other
      component (the prey) is fused to the protein of interest. Upon illumination,
      binding of the prey to the bait results in its subcellular redistribution. Here,
      we compared and quantified the extent of light-dependent dimer occurrence in
      small, subcellular volumes controlled by three such tools: Cry2/CIB1, iLID, and
      Magnets. We show that both the location of the photoreceptor protein(s) in the
      dimer pair and its (their) switch-off kinetics determine the subcellular volume
      where dimer formation occurs and the amount of protein recruited in the
      illuminated volume. Efficient spatial confinement of dimer to the area of
      illumination is achieved when the photosensitive component of the dimerization
      pair is tethered to the membrane of intracellular compartments and when on and
      off kinetics are extremely fast, as achieved with iLID or Magnets. Magnets and
      the iLID variants with the fastest switch-off kinetics induce and maintain
      protein dimerization in the smallest volume, although this comes at the expense
      of the total amount of dimer. These findings highlight the distinct features of
      different optical dimerization systems and will be useful guides in the choice of
      tools for specific applications.

PMID- 29463753
TI  - Signal peptide of HIV envelope protein impacts glycosylation and antigenicity of
      gp120.
AB  - The HIV-1 envelope protein (Env) of early-replicating viruses encodes several
      distinct transmission signatures. One such signature involves a reduced number of
      potential N-linked glycosylation sites (PNGs). This transmission signature
      underscores the importance of posttranslational modifications in the fitness of
      early-replicating isolates. An additional signature in Env involves the
      overrepresentation of basic amino acid residues at a specific position in the Env
      signal peptide (SP). In this report, we investigated the potential impact of this
      SP signature on gp120 glycosylation and antigenicity. Two recombinant gp120s were
      constructed, one derived from an isolate that lacks this signature and a second
      from an early-replicating isolate that includes this signature. Chimeric gp120s
      were also constructed in which the two SPs were swapped between the isolates. All
      four gp120s were probed with glycan-, structure- and receptor- specific probes in
      a surface plasmon resonance binding assay. We found that the SP of Env influences
      qualitative aspects of Env glycosylation that in turn affect the antigenicity of
      Env in a major way. The SP impacts the affinity of Env for DC-SIGN, a lectin
      receptor expressed on dendritic cells that is believed to play a role in mucosal
      transmission. Additionally, affinity for the monoclonal antibodies 17b and A32,
      which recognize a CD4-induced, open conformation of Env is also altered. These
      results demonstrate that natural variation in the SP of HIV Env can significantly
      impact the antigenicity of mature gp120. Thus, the SP is likely subject to
      antibody-mediated immune pressure.

PMID- 29463755
TI  - Crop intensification, land use, and on-farm energy-use efficiency during the
      worldwide spread of the green revolution.
AB  - We analyzed crop production, physical inputs, and land use at the country level
      to assess technological changes behind the threefold increase in global crop
      production from 1961 to 2014. We translated machinery, fuel, and fertilizer to
      embedded energy units that, when summed up, provided a measure of agricultural
      intensification (human subsidy per hectare) for crops in the 58 countries
      responsible for 95% of global production. Worldwide, there was a 137% increase in
      input use per hectare, reaching 13 EJ, or 2.6% of the world's primary energy
      supply, versus only a 10% increase in land use. Intensification was marked in
      Asia and Latin America, where input-use levels reached those that North America
      and Europe had in the earlier years of the period; the increase was more
      accentuated, irrespective of continent, for the 12 countries with mostly
      irrigated production. Half of the countries (28/58), mainly developed ones, had
      an average subsidy >5 GJ/ha/y (with fertilizers accounting for 27% in 1961 and
      45% in 2014), with most of them (23/28) using about the same area or less than in
      1961 (net land sparing of 31 Mha). Most of the remaining countries (24/30 with
      inputs <5 GJ/ha/y), mainly developing ones, increased their cropped area (net
      land extensification of 135 Mha). Overall, energy-use efficiency (crop
      output/inputs) followed a U-shaped trajectory starting at about 3 and finishing
      close to 4. The prospects of a more sustainable intensification are discussed,
      and the inadequacy of the land-sparing model expectation of protecting wilderness
      via intensified agriculture is highlighted.

PMID- 29463754
TI  - Translational control in the tumor microenvironment promotes lung metastasis:
      Phosphorylation of eIF4E in neutrophils.
AB  - The translation of mRNAs into proteins serves as a critical regulatory event in
      gene expression. In the context of cancer, deregulated translation is a hallmark
      of transformation, promoting the proliferation, survival, and metastatic
      capabilities of cancer cells. The best-studied factor involved in the
      translational control of cancer is the eukaryotic translation initiation factor
      4E (eIF4E). We and others have shown that eIF4E availability and phosphorylation
      promote metastasis in mouse models of breast cancer by selectively augmenting the
      translation of mRNAs involved in invasion and metastasis. However, the impact of
      translational control in cell types within the tumor microenvironment (TME) is
      unknown. Here, we demonstrate that regulatory events affecting translation in
      cells of the TME impact cancer progression. Mice bearing a mutation in the
      phosphorylation site of eIF4E (S209A) in cells comprising the TME are resistant
      to the formation of lung metastases in a syngeneic mammary tumor model. This is
      associated with reduced survival of prometastatic neutrophils due to decreased
      expression of the antiapoptotic proteins BCL2 and MCL1. Furthermore, we
      demonstrate that pharmacological inhibition of eIF4E phosphorylation prevents
      metastatic progression in vivo, supporting the development of phosphorylation
      inhibitors for clinical use.

PMID- 29463756
TI  - Diagnostic utility of telomere length testing in a hospital-based setting.
AB  - Telomere length (TL) predicts the onset of cellular senescence in vitro but the
      diagnostic utility of TL measurement in clinical settings is not fully known. We
      tested the value of TL measurement by flow cytometry and FISH (flowFISH) in
      patients with mutations in telomerase and telomere maintenance genes. TL had a
      discrete and reproducible normal range with definable upper and lower boundaries.
      While TL above the 50th age-adjusted percentile had a 100% negative predictive
      value for clinically relevant mutations, the lower threshold in mutation carriers
      was age-dependent, and adult mutation carriers often overlapped with the lowest
      decile of controls. The extent of telomere shortening correlated with the age at
      diagnosis as well as the short telomere syndrome phenotype. Extremely short TL
      caused bone marrow failure and immunodeficiency in children and young adults,
      while milder defects manifested as pulmonary fibrosis-emphysema in adults. We
      prospectively examined whether TL altered treatment decisions for newly diagnosed
      idiopathic bone marrow failure patients and found abnormally short TL enriched
      for patients with mutations in some inherited bone marrow failure genes, such as
      RUNX1, in addition to telomerase and telomere maintenance genes. The result was
      actionable, altering the choice of treatment regimen and/or hematopoietic stem
      cell donor in one-fourth of the cases (9 of 38, 24%). We conclude that TL
      measurement by flowFISH, when used for targeted clinical indications and in
      limited settings, can influence treatment decisions in ways that improve outcome.

PMID- 29463758
TI  - Profile of Michael Strand.

PMID- 29463757
TI  - Prospective forecasts of annual dengue hemorrhagic fever incidence in Thailand,
      2010-2014.
AB  - Dengue hemorrhagic fever (DHF), a severe manifestation of dengue viral infection
      that can cause severe bleeding, organ impairment, and even death, affects between
      15,000 and 105,000 people each year in Thailand. While all Thai provinces
      experience at least one DHF case most years, the distribution of cases shifts
      regionally from year to year. Accurately forecasting where DHF outbreaks occur
      before the dengue season could help public health officials prioritize public
      health activities. We develop statistical models that use biologically plausible
      covariates, observed by April each year, to forecast the cumulative DHF incidence
      for the remainder of the year. We perform cross-validation during the training
      phase (2000-2009) to select the covariates for these models. A parsimonious model
      based on preseason incidence outperforms the 10-y median for 65% of province
      level annual forecasts, reduces the mean absolute error by 19%, and successfully
      forecasts outbreaks (area under the receiver operating characteristic curve =
      0.84) over the testing period (2010-2014). We find that functions of past
      incidence contribute most strongly to model performance, whereas the importance
      of environmental covariates varies regionally. This work illustrates that
      accurate forecasts of dengue risk are possible in a policy-relevant timeframe.

PMID- 29463759
TI  - Axogenic mechanism enhances retinal ganglion cell excitability during early
      progression in glaucoma.
AB  - Diseases of the brain involve early axon dysfunction that often precedes outright
      degeneration. Pruning of dendrites and their synapses represents a potential
      driver of axonopathy by reducing activity. Optic nerve degeneration in glaucoma,
      the world's leading cause of irreversible blindness, involves early stress to
      retinal ganglion cell (RGC) axons from sensitivity to intraocular pressure (IOP).
      This sensitivity also influences survival of RGC dendrites and excitatory
      synapses in the retina. Here we tested in individual RGCs identified by type the
      relationship between dendritic organization and axon signaling to light following
      modest, short-term elevations in pressure. We found dendritic pruning occurred
      early, by 2 wk of elevation, and independent of whether the RGC responded to
      light onset (ON cells) or offset (OFF cells). Pruning was similarly independent
      of ON and OFF in the DBA/2J mouse, a chronic glaucoma model. Paradoxically, all
      RGCs, even those with significant pruning, demonstrated a transient increase in
      axon firing in response to the preferred light stimulus that occurred on a
      backdrop of generally enhanced excitability. The increased response was not
      through conventional presynaptic signaling, but rather depended on voltage
      sensitive sodium channels that increased transiently in the axon. Pruning, axon
      dysfunction, and deficits in visual acuity did not progress between 2 and 4 wk of
      elevation. These results suggest neurodegeneration in glaucoma involves an early
      axogenic response that counters IOP-related stress to excitatory dendritic
      architecture to slow progression and maintain signaling to the brain. Thus, short
      term exposure to elevated IOP may precondition the neural system to further
      insult.

PMID- 29463760
TI  - A comprehensive model for the proliferation-quiescence decision in response to
      endogenous DNA damage in human cells.
AB  - Human cells that suffer mild DNA damage can enter a reversible state of growth
      arrest known as quiescence. This decision to temporarily exit the cell cycle is
      essential to prevent the propagation of mutations, and most cancer cells harbor
      defects in the underlying control system. Here we present a mechanistic
      mathematical model to study the proliferation-quiescence decision in
      nontransformed human cells. We show that two bistable switches, the restriction
      point (RP) and the G1/S transition, mediate this decision by integrating DNA
      damage and mitogen signals. In particular, our data suggest that the cyclin
      dependent kinase inhibitor p21 (Cip1/Waf1), which is expressed in response to DNA
      damage, promotes quiescence by blocking positive feedback loops that facilitate
      G1 progression downstream of serum stimulation. Intriguingly, cells exploit
      bistability in the RP to convert graded p21 and mitogen signals into an all-or
      nothing cell-cycle response. The same mechanism creates a window of opportunity
      where G1 cells that have passed the RP can revert to quiescence if exposed to DNA
      damage. We present experimental evidence that cells gradually lose this ability
      to revert to quiescence as they progress through G1 and that the onset of rapid
      p21 degradation at the G1/S transition prevents this response altogether,
      insulating S phase from mild, endogenous DNA damage. Thus, two bistable switches
      conspire in the early cell cycle to provide both sensitivity and robustness to
      external stimuli.

PMID- 29463762
TI  - From global scaling to the dynamics of individual cities.
AB  - Scaling has been proposed as a powerful tool to analyze the properties of complex
      systems and in particular for cities where it describes how various properties
      change with population. The empirical study of scaling on a wide range of urban
      datasets displays apparent nonlinear behaviors whose statistical validity and
      meaning were recently the focus of many debates. We discuss here another aspect,
      which is the implication of such scaling forms on individual cities and how they
      can be used for predicting the behavior of a city when its population changes. We
      illustrate this discussion in the case of delay due to traffic congestion with a
      dataset of 101 US cities in the years 1982-2014. We show that the scaling form
      obtained by agglomerating all of the available data for different cities and for
      different years does display a nonlinear behavior, but which appears to be
      unrelated to the dynamics of individual cities when their population grows. In
      other words, the congestion-induced delay in a given city does not depend on its
      population only, but also on its previous history. This strong path dependency
      prohibits the existence of a simple scaling form valid for all cities and shows
      that we cannot always agglomerate the data for many different systems. More
      generally, these results also challenge the use of transversal data for
      understanding longitudinal series for cities.

PMID- 29463761
TI  - Cooption of heat shock regulatory system for anhydrobiosis in the sleeping
      chironomid Polypedilum vanderplanki.
AB  - Polypedilum vanderplanki is a striking and unique example of an insect that can
      survive almost complete desiccation. Its genome and a set of dehydration
      rehydration transcriptomes, together with the genome of Polypedilum nubifer (a
      congeneric desiccation-sensitive midge), were recently released. Here, using
      published and newly generated datasets reflecting detailed transcriptome changes
      during anhydrobiosis, as well as a developmental series, we show that the TCTAGAA
      DNA motif, which closely resembles the binding motif of the Drosophila
      melanogaster heat shock transcription activator (Hsf), is significantly enriched
      in the promoter regions of desiccation-induced genes in P. vanderplanki, such as
      genes encoding late embryogenesis abundant (LEA) proteins, thioredoxins, or
      trehalose metabolism-related genes, but not in P. nubifer Unlike P. nubifer, P.
      vanderplanki has double TCTAGAA sites upstream of the Hsf gene itself, which is
      probably responsible for the stronger activation of Hsf in P. vanderplanki during
      desiccation compared with P. nubifer To confirm the role of Hsf in desiccation
      induced gene activation, we used the Pv11 cell line, derived from P. vanderplanki
      embryo. After preincubation with trehalose, Pv11 cells can enter anhydrobiosis
      and survive desiccation. We showed that Hsf knockdown suppresses trehalose
      induced activation of multiple predicted Hsf targets (including P. vanderplanki
      specific LEA protein genes) and reduces the desiccation survival rate of Pv11
      cells fivefold. Thus, cooption of the heat shock regulatory system has been an
      important evolutionary mechanism for adaptation to desiccation in P.
      vanderplanki.

PMID- 29463763
TI  - Irreversible inactivation of ISG15 by a viral leader protease enables alternative
      infection detection strategies.
AB  - In response to viral infection, cells mount a potent inflammatory response that
      relies on ISG15 and ubiquitin posttranslational modifications. Many viruses use
      deubiquitinases and deISGylases that reverse these modifications and antagonize
      host signaling processes. We here reveal that the leader protease, Lbpro, from
      foot-and-mouth disease virus (FMDV) targets ISG15 and to a lesser extent,
      ubiquitin in an unprecedented manner. Unlike canonical deISGylases that hydrolyze
      the isopeptide linkage after the C-terminal GlyGly motif, Lbpro cleaves the
      peptide bond preceding the GlyGly motif. Consequently, the GlyGly dipeptide
      remains attached to the substrate Lys, and cleaved ISG15 is rendered incompetent
      for reconjugation. A crystal structure of Lbpro bound to an engineered ISG15
      suicide probe revealed the molecular basis for ISG15 proteolysis. Importantly,
      anti-GlyGly antibodies, developed for ubiquitin proteomics, are able to detect
      Lbpro cleavage products during viral infection. This opens avenues for infection
      detection of FMDV based on an immutable, host-derived epitope.

PMID- 29463765
TI  - T-CARQ: a BASHH trainee collaborative for audit, research and quality
      improvement.

PMID- 29463766
TI  - Use of condoms: pitfalls of retrospective case-note analysis.

PMID- 29463767
TI  - Kissing while high on ecstasy: lessons from a gay dance party attendee.

PMID- 29463764
TI  - Functional and physical interaction between yeast Hsp90 and Hsp70.
AB  - Heat shock protein 90 (Hsp90) is a highly conserved ATP-dependent molecular
      chaperone that is essential in eukaryotes. It is required for the activation and
      stabilization of more than 200 client proteins, including many kinases and
      steroid hormone receptors involved in cell-signaling pathways. Hsp90 chaperone
      activity requires collaboration with a subset of the many Hsp90 cochaperones,
      including the Hsp70 chaperone. In higher eukaryotes, the collaboration between
      Hsp90 and Hsp70 is indirect and involves Hop, a cochaperone that interacts with
      both Hsp90 and Hsp70. Here we show that yeast Hsp90 (Hsp82) and yeast Hsp70
      (Ssa1), directly interact in vitro in the absence of the yeast Hop homolog
      (Sti1), and identify a region in the middle domain of yeast Hsp90 that is
      required for the interaction. In vivo results using Hsp90 substitution mutants
      showed that several residues in this region were important or essential for
      growth at high temperature. Moreover, mutants in this region were defective in
      interaction with Hsp70 in cell lysates. In vitro, the purified Hsp82 mutant
      proteins were defective in direct physical interaction with Ssa1 and in protein
      remodeling in collaboration with Ssa1 and cochaperones. This region of Hsp90 is
      also important for interactions with several Hsp90 cochaperones and client
      proteins, suggesting that collaboration between Hsp70 and Hsp90 in protein
      remodeling may be modulated through competition between Hsp70 and Hsp90
      cochaperones for the interaction surface.

PMID- 29463768
TI  - Ethical implications of excessive cluster sizes in cluster randomised trials.
AB  - The cluster randomised trial (CRT) is commonly used in healthcare research. It is
      the gold-standard study design for evaluating healthcare policy interventions. A
      key characteristic of this design is that as more participants are included, in a
      fixed number of clusters, the increase in achievable power will level off. CRTs
      with cluster sizes that exceed the point of levelling-off will have excessive
      numbers of participants, even if they do not achieve nominal levels of power.
      Excessively large cluster sizes may have ethical implications due to exposing
      trial participants unnecessarily to the burdens of both participating in the
      trial and the potential risks of harm associated with the intervention. We
      explore these issues through the use of two case studies. Where data are
      routinely collected, available at minimum cost and the intervention poses low
      risk, the ethical implications of excessively large cluster sizes are likely to
      be low (case study 1). However, to maximise the social benefit of the study,
      identification of excessive cluster sizes can allow for prespecified and fully
      powered secondary analyses. In the second case study, while there is no burden
      through trial participation (because the outcome data are routinely collected and
      non-identifiable), the intervention might be considered to pose some indirect
      risk to patients and risks to the healthcare workers. In this case study it is
      therefore important that the inclusion of excessively large cluster sizes is
      justifiable on other grounds (perhaps to show sustainability). In any randomised
      controlled trial, including evaluations of health policy interventions, it is
      important to minimise the burdens and risks to participants. Funders, researchers
      and research ethics committees should be aware of the ethical issues of
      excessively large cluster sizes in cluster trials.

PMID- 29463769
TI  - Pilot randomised controlled trial to improve hand hygiene through mindful
      moments.
AB  - BACKGROUND: To evaluate the effectiveness of a brief mindfulness intervention on
      hand hygiene performance and mindful attention for inpatient physician teams.
      DESIGN: A pilot, pre-test/post-test randomised controlled mixed methods trial.
      SETTING: One academic medical centre in the USA. PARTICIPANTS: Four internal
      medicine physician teams consisting of one attending, one resident, two to three
      interns and up to four medical students. INTERVENTION: A facilitated, group-based
      educational discussion on how mindfulness, as practised through mindful hand
      hygiene, may improve clinical care and practices in the hospital setting. MAIN
      OUTCOMES AND MEASURES: The primary outcome was hand hygiene adherence
      (percentage) for each patient encounter. Other outcomes were observable mindful
      moments and mindful attention, measured using the Mindfulness Attention Awareness
      Scale, from baseline to post-intervention, and qualitative evaluation of the
      intervention. RESULTS: For attending physicians, hand hygiene adherence increased
      14.1% in the intervention group compared with a decrease of 5.7% in the controls
      (P=0.035). For residents, the comparable figures were 24.7% (intervention) versus
      0.2% (control) (P=0.064). For interns, adherence increased 10.0% with the
      intervention versus 4.2% in the controls (P=0.007). For medical students,
      adherence improved more in the control group (4.7% intervention vs 7.7% controls;
      P=0.003). An increase in mindfulness behaviours was observed for the intervention
      group (3.7%) versus controls (0.9%) (P=0.021). Self-reported mindful attention
      did not change (P=0.865). CONCLUSIONS: A brief, education-based mindfulness
      intervention improved hand hygiene in attending physicians and residents, but not
      in medical students. The intervention was well-received, increased mindfulness
      practice, and appears to be a feasible way to introduce mindfulness in the
      clinical setting. Future work instructing clinicians in mindfulness to improve
      hand hygiene may prove valuable. TRIAL REGISTRATION NUMBER: NCT 03165799;
      Results.

PMID- 29463770
TI  - Using ethnography to study improving healthcare: reflections on the
      'ethnographic' label.

PMID- 29463771
TI  - STRESS INDUCED FACTOR 2, a Leucine-Rich Repeat Kinase Regulates Basal Plant
      Pathogen Defense.
AB  - Protein kinases play fundamental roles in plant development and environmental
      stress responses. Here, we identified the STRESS INDUCED FACTOR (SIF) gene
      family, which encodes four leucine-rich repeat receptor-like protein kinases in
      Arabidopsis (Arabidopsis thaliana). The four genes, SIF1 to SIF4, are clustered
      in the genome and highly conserved, but they have temporally and spatially
      distinct expression patterns. We employed Arabidopsis SIF knockout mutants and
      overexpression transgenics to examine SIF involvement during plant pathogen
      defense. SIF genes are rapidly induced by biotic or abiotic stresses, and SIF
      proteins localize to the plasma membrane. Simultaneous knockout of SIF1 and SIF2
      led to improved plant salt tolerance, whereas SIF2 overexpression enhanced PAMP
      triggered immunity and prompted basal plant defenses, significantly improving
      pathogen resistance. Furthermore, SIF2 overexpression plants exhibited up
      regulated expression of the defense-related genes WRKY53 and flg22-INDUCED
      RECEPTOR-LIKE KINASE1 as well as enhanced MPK3/MPK6 phosphorylation upon pathogen
      and elicitor treatments. The expression of the calcium signaling-related gene
      PHOSPHATE-INDUCED1 also was enhanced in the SIF2-overexpressing lines upon
      pathogen inoculation but repressed in the sif2 mutants. Bimolecular fluorescence
      complementation demonstrates that the BRI1-ASSOCIATED RECEPTOR KINASE1 protein is
      a coreceptor of the SIF2 kinase in the signal transduction pathway during
      pathogen invasion. These findings characterize a stress-responsive protein kinase
      family and illustrate how SIF2 modulates signal transduction for effective plant
      pathogenic defense.

PMID- 29463772
TI  - Proliferation of Regulatory DNA Elements Derived from Transposable Elements in
      the Maize Genome.
AB  - Genomic regions free of nucleosomes, which are hypersensitive to DNase I
      digestion, are known as DNase I hypersensitive sites (DHSs) and frequently
      contain cis-regulatory DNA elements. To investigate their prevalence and
      characteristics in maize (Zea mays), we developed high-resolution genome-wide DHS
      maps using a modified DNase-seq technique. Maize DHSs exhibit depletion of
      nucleosomes and low levels of DNA methylation and are enriched with conserved
      noncoding sequences (CNSs). We developed a protoplast-based transient
      transformation assay to assess the potential gene expression enhancer and/or
      promoter functions associated with DHSs, which showed that more than 80% of DHSs
      overlapping with CNSs showed an enhancer function. Strikingly, nearly 25% of
      maize DHSs were derived from transposable elements (TEs), including both class I
      and class II transposons. Interestingly, TE-derived DHSs (teDHSs) homologous to
      retrotransposons were enriched with sequences related to the intrinsic cis
      regulatory elements within the long terminal repeats of retrotransposons. We
      demonstrate that more than 80% of teDHSs can drive transcription of a reporter
      gene in protoplast assays. These results reveal the widespread occurrence of TE
      derived cis-regulatory sequences and suggest that teDHSs play a major role in
      transcriptional regulation in maize.

PMID- 29463773
TI  - The Citrus Transcription Factor CsMADS6 Modulates Carotenoid Metabolism by
      Directly Regulating Carotenogenic Genes.
AB  - Although remarkable progress has been made toward understanding carotenoid
      biosynthesis, the mechanisms that regulate the transcription of carotenogenic
      genes remain poorly understood. Lycopene beta-cyclases (LCYb) are critical
      enzymes located at the branch point of the carotenoid biosynthetic pathway. Here,
      we used the promoter sequence of LCYb1 as bait in a yeast one-hybrid screen for
      promoter-binding proteins from sweet orange (Citrus sinensis). This screen
      identified a MADS transcription factor, CsMADS6, that was coordinately expressed
      with fruit development and coloration. Acting as a nucleus-localized
      transcriptional activator, CsMADS6 directly bound the promoter of LCYb1 and
      activated its expression. Overexpression of CsMADS6 in citrus calli increased
      carotenoid contents and induced the expression of LCYb1 and other carotenogenic
      genes, including phytoene synthase (PSY), phytoene desaturase (PDS), and
      carotenoid cleavage dioxygenase1 (CCD1). CsMADS6 up-regulated the expression of
      PSY, PDS, and CCD1 by directly binding to their promoters, which suggested the
      multitargeted regulation of carotenoid metabolism by CsMADS6. In addition, the
      ectopic expression of CsMADS6 in tomato (Solanum lycopersicum) affected
      carotenoid contents and the expression of carotenogenic genes. The sepals of
      CsMADS6-overexpressing tomato lines exhibited dramatic changes in carotenoid
      profiles, accompanied by changes in plastid ultrastructure. Global transcriptome
      analysis of transgenic sepals revealed that CsMADS6 regulates a series of
      pathways that promote increases in flux through the carotenoid pathway. Overall,
      these findings establish that CsMADS6 directly regulates LCYb1 and other
      carotenogenic genes to coordinately and positively modulate carotenoid metabolism
      in plants, which may provide strategies to improve the nutritional quality of
      crops.

PMID- 29463774
TI  - The Ribosome-Bound Protein Pam68 Promotes Insertion of Chlorophyll into the CP47
      Subunit of Photosystem II.
AB  - Photosystem II (PSII) is a large enzyme complex embedded in the thylakoid
      membrane of oxygenic phototrophs. The biogenesis of PSII requires the assembly of
      more than 30 subunits, with the assistance of a number of auxiliary proteins. In
      plants and cyanobacteria, the photosynthesis-affected mutant 68 (Pam68) is
      important for PSII assembly. However, its mechanisms of action remain unknown.
      Using a Synechocystis PCC 6803 strain expressing Flag-tagged Pam68, we purified a
      large protein complex containing ribosomes, SecY translocase, and the chlorophyll
      binding PSII inner antenna CP47. Using 2D gel electrophoresis, we identified a
      pigmented Pam68-CP47 subcomplex and found Pam68 bound to ribosomes. Our results
      show that Pam68 binds to ribosomes even in the absence of CP47 translation.
      Furthermore, Pam68 associates with CP47 at an early phase of its biogenesis and
      promotes the synthesis of this chlorophyll-binding polypeptide until the
      attachment of the small PSII subunit PsbH. Deletion of both Pam68 and PsbH nearly
      abolishes the synthesis of CP47, which can be restored by enhancing chlorophyll
      biosynthesis. These results strongly suggest that ribosome-bound Pam68 stabilizes
      membrane segments of CP47 and facilitates the insertion of chlorophyll molecules
      into the translated CP47 polypeptide chain.

PMID- 29463776
TI  - Abl and Arg mediate cysteine cathepsin secretion to facilitate melanoma invasion
      and metastasis.
AB  - The incidence of melanoma is increasing, particularly in young women, and the
      disease remains incurable for many because of its aggressive, metastatic nature
      and its high rate of resistance to conventional, targeted, and immunological
      agents. Cathepsins are proteases that are critical for melanoma progression and
      therapeutic resistance. Intracellular cathepsins cleave or degrade proteins that
      restrict cancer progression, whereas extracellular cathepsins directly cleave the
      extracellular matrix and activate proinvasive proteases in the tumor
      microenvironment. Cathepsin secretion is markedly increased in cancer cells. We
      investigated the signaling pathways leading to increased cathepsin secretion in
      melanoma cells. We found that the nonreceptor tyrosine kinases Abl and Arg
      (Abl/Arg) promoted the secretion of cathepsin B and cathepsin L by activating
      transcription factors (namely, Ets1, Sp1, and NF-kappaB/p65) that have key roles
      in the epithelial-mesenchymal transition (EMT), invasion, and therapeutic
      resistance. In some melanoma cell lines, Abl/Arg promoted the Ets1/p65-induced
      secretion of cathepsin B and cathepsin L in a kinase-independent manner, whereas
      in other melanoma lines, Abl/Arg promoted the kinase-dependent, Sp1/Ets1/p65
      mediated induction of cathepsin L secretion and the Sp1/p65-mediated induction of
      cathepsin B secretion. As an indication of clinical relevance, the abundance of
      mRNAs encoding Abl/Arg, Sp1, Ets1, and cathepsins was positively correlated in
      primary melanomas, and Abl/Arg-driven invasion in culture and metastasis in vivo
      required cathepsin secretion. These data suggest that drugs targeting Abl
      kinases, many of which are FDA-approved, might inhibit cathepsin secretion in
      some melanomas and potentially other aggressive cancers harboring activated Abl
      kinases.

PMID- 29463775
TI  - The Transcriptional Coactivator ADA2b Recruits a Structural Maintenance Protein
      to Double-Strand Breaks during DNA Repair in Plants.
AB  - DNA damage occurs in all cells and can hinder chromosome stability and cell
      viability. Structural Maintenance of Chromosomes5/6 (SMC5/6) is a protein complex
      that functions as an evolutionarily conserved chromosomal ATPase critical for
      repairing DNA double-strand breaks (DSBs). However, the mechanisms regulating
      this complex in plants are poorly understood. Here, we identified the
      transcriptional coactivator ALTERATION/DEFICIENCY IN ACTIVATION2B (ADA2b) as an
      interactor of SMC5 in Arabidopsis (Arabidopsis thaliana). ADA2b is a conserved
      component of the Spt-Ada-Gcn5 acetyltransferase complex, which functions in
      transcriptional regulation. Characterization of mutant and knockdown Arabidopsis
      lines showed that disruption of either SMC5 or ADA2b resulted in enhanced DNA
      damage. Both SMC5 and ADA2b were associated with gamma-H2AX, a marker of DSBs,
      and the recruitment of SMC5 onto DSBs was dependent on ADA2b. In addition,
      overexpression of SMC5 in the ada2b mutant background stimulated cell death.
      Collectively, our results show that the interaction between ADA2b and SMC5
      mediates DNA repair in plant cells, suggesting a functional association between
      these conserved proteins and further elucidating mechanisms of DNA damage repair
      in plants.

PMID- 29463777
TI  - The intracellular pyrimidine 5'-nucleotidase NT5C3A is a negative epigenetic
      factor in interferon and cytokine signaling.
AB  - The enzyme pyrimidine 5'-nucleotidase (NT5C3A), which mediates nucleotide
      catabolism, was previously thought to be restricted to blood cells. We showed
      that expression of the gene encoding NT5C3A was induced by type I interferons
      (IFNs) in multiple cell types and that NT5C3A suppressed cytokine production
      through inhibition of the nuclear factor kappaB (NF-kappaB) pathway. NT5C3A
      expression required both an intronic IFN-stimulated response element and the IFN
      stimulated transcription factor IRF1. Overexpression of NT5C3A, but not of its
      catalytic mutants, suppressed IL-8 production by HEK293 cells. Whereas knockdown
      of NT5C3A enhanced tumor necrosis factor (TNF)-stimulated IL-8 production, it
      reduced the IFN-mediated suppression of Il8 expression. Overexpression of NT5C3A
      increased the abundance of NAD+ and the activation of the sirtuins SIRT1 and
      SIRT6, which are NAD+-dependent deacetylases. NT5C3A-stimulated sirtuin activity
      resulted in deacetylation of histone H3 and the NF-kappaB subunit RelA (also
      known as p65), both of which were associated with the proximal region of the Il8
      promoter, thus repressing the transcription of Il8 Together, these data identify
      an anti-inflammatory pathway that depends on the catalytic activity of NT5C3A and
      functions as a negative feedback regulator of inflammatory cytokine signaling.

PMID- 29463779
TI  - Coordinating the overall stomatal response of plants: Rapid leaf-to-leaf
      communication during light stress.
AB  - The plant canopy functions as an aerial array of light-harvesting antennas. To
      achieve maximal yield, each leaf within this array and the array as a whole need
      to rapidly adjust to naturally occurring fluctuations in light intensity and
      quality. Excessive light stress triggers the closing of pores in leaves called
      stomata to minimize moisture loss. We found that different leaves within the
      canopy of an Arabidopsis thaliana plant, including leaves not directly exposed to
      light, coordinated stomatal closure in response to light stress by sending and
      receiving rapid systemic signals. This response required the plant hormones
      abscisic acid and jasmonic acid and was mediated by a rapid autopropagating wave
      of reactive oxygen species (ROS) production. Furthermore, this response depended
      on the function of genes encoding the ROS-generating NADPH oxidase RBOHD and
      various stomatal regulators, such as the anion channel SLAC1, GHR1 (guard cell
      hydrogen peroxide resistant 1), and lipoxygenase 1 (LOX1). Our findings reveal
      that plants function as highly dynamic and coordinated organisms, optimizing the
      overall response of their canopies to fluctuating light intensities.

PMID- 29463778
TI  - A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane
      salt bridge to activate beta-arrestin-biased signaling.
AB  - The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) that
      signals through Gq/11 and Gi/o to stimulate cytosolic calcium (Ca2+i) and mitogen
      activated protein kinase (MAPK) signaling to control extracellular calcium
      homeostasis. Studies of loss- and gain-of-function CASR mutations, which cause
      familial hypocalciuric hypercalcemia type 1 (FHH1) and autosomal dominant
      hypocalcemia type 1 (ADH1), respectively, have revealed that the CaSR signals in
      a biased manner. Thus, some mutations associated with FHH1 lead to signaling
      predominantly through the MAPK pathway, whereas mutations associated with ADH1
      preferentially enhance Ca2+i responses. We report a previously unidentified ADH1
      associated R680G CaSR mutation, which led to the identification of a CaSR
      structural motif that mediates biased signaling. Expressing CaSRR680G in HEK 293
      cells showed that this mutation increased MAPK signaling without altering Ca2+i
      responses. Moreover, this gain of function in MAPK activity occurred
      independently of Gq/11 and Gi/o and was mediated instead by a noncanonical
      pathway involving beta-arrestin proteins. Homology modeling and mutagenesis
      studies showed that the R680G CaSR mutation selectively enhanced beta-arrestin
      signaling by disrupting a salt bridge formed between Arg680 and Glu767, which are
      located in CaSR transmembrane domain 3 and extracellular loop 2, respectively.
      Thus, our results demonstrate CaSR signaling through beta-arrestin and the
      importance of the Arg680-Glu767 salt bridge in mediating signaling bias.

PMID- 29463780
TI  - Science and Culture: Quantum games aim to demystify heady science.

PMID- 29463782
TI  - Endogenous volatile organic compounds in acute myeloid leukemia: origins and
      potential clinical applications.
AB  - Not unlike many cancer types, acute myeloid leukemia (AML) exhibits many
      metabolic changes and reprogramming, causing changes in lipid metabolism. Some of
      the distinct molecular abnormalities associated with AML also modify the
      metabolic changes. Both processes result in changes in the production of
      endogenous volatile organic compounds (VOCs). The increasing availability of
      highly sensitive methods for detecting trace chemicals provides the opportunity
      to investigate the role of patient-specific VOC finger-prints as biomarkers for
      detecting early relapse or minimal residual disease in AML. Since VOC production
      is reliant on metabolic activities, when combined with currently available
      methods, VOC analysis may identify within a group of patients with flow
      cytometric or molecular evidence of residual disease those most at risk for
      disease relapse.

PMID- 29463783
TI  - Comparison of Percutaneous Kyphoplasty and Bone Cement-Augmented Short-Segment
      Pedicle Screw Fixation for Management of Kummell Disease.
AB  - BACKGROUND The purpose of this study was to compare the efficacy of percutaneous
      kyphoplasty (PKP) and bone cement-augmented short segmental fixation (BCA+SSF)
      for treating Kummell disease. MATERIAL AND METHODS Between June 2013 and December
      2015, 60 patients were treated with PKP or BCA+SSF. All patients were followed up
      for 12-36 months. We retrospectively reviewed outcomes, including Oswestry
      Disability Index (ODI), visual analogue scale (VAS), and kyphotic Cobb angle.
      RESULTS VAS, ODI, and Cobb angle, measured postoperatively and at the final
      follow-up, were lower than those measured preoperatively in both groups (P<0.05).
      VAS, ODI, and Cobb angle measured postoperatively demonstrated no significant
      differences when compared with those measured at the final follow-up in the PKP
      group (P>0.05). In the BCA+SSF group, VAS and ODI at the final follow-up were
      lower than those measured postoperatively (P<0.05), but no significant difference
      was found in the Cobb angle (P>0.05). The PKP group had better VAS and ODI than
      the BCA+SSF group, postoperatively (P<0.05). No significant difference was found
      in VAS and ODI at the final follow-up (P>0.05) or the Cobb angle measured
      postoperatively and at the final follow-up (P>0.05) between the 2 groups.
      Operative time, blood loss, and hospital stay in the PKP group were lower than
      those in the BCA+SSF group (P<0.05). No significant difference was found in
      complications (P>0.05). CONCLUSIONS PKP patients had better early clinical
      outcomes, shorter operation times and hospital admission times, and decreased
      blood loss, but had similar complications, radiographic results, and long-term
      clinical outcomes compared with BCA+SSF patients.

PMID- 29463784
TI  - Severe Fetal Distress and Placental Damage might be Associated with High Troponin
      I (cTnI) Levels in Mothers.
AB  - BACKGROUND Troponin I is the gold standard for the diagnosis of adult acute
      coronary syndrome. Although it is known that a hypoxic fetus may produce cTnI,
      fetal cTnI passage in maternal blood has never been documented. CASE REPORT We
      report a case where the rise of cTnI in the blood of a pregnant woman was not
      related to maternal heart disease. Instead, it might be suggestive of a fetal
      cardiac origin, as there was a severe placental insufficiency with a fetal
      intrauterine growth restriction. CONCLUSIONS This study suggests that the rise of
      cTnI in maternal blood in a cardiovascular healthy pregnant woman might have a
      fetal origin. After having excluded any maternal causes, cTnI elevation could be
      explained with the transfer of fetal cTnI through an injured placenta.

PMID- 29463785
TI  - Dysfunctional immunoregulation in human liver allograft rejection associated with
      compromised galectin-1/CD7 pathway function.
AB  - Regulatory T cells in rejected allograft patients display an inability to control
      responder T cells. Galectin-1 (Gal1) inhibits responder T cells through binding
      CD7. We investigated whether the dysfunctional immunoregulation in liver
      allograft rejection patients results from reduced regulatory T-cell Gal1
      expression and/or responder T-cell CD7 expression. Circulating regulatory T cells
      and responder T cells were profiled from 31 acute rejection transplant patients,
      85 transplant patients in remission, and 40 healthy controls. CD7+ and CD7-
      responder T cells were co-cultured with regulatory T cells to assess regulatory T
      cell suppressor function. Gal1-small interfering RNA was used to silence
      regulatory T-cell Gal1. The CD7+ cell percentage was inversely correlated with
      AST, ALT, and GGT levels. The proportions of CD7+ responder T cells and Gal1+
      regulatory T cells were higher in healthy controls than in transplant patients in
      remission and lowest in acute rejection transplant patients. Notably, CD7+
      responder T-cell susceptibility to Gal1+ regulatory T-cell control was ranked in
      the same manner. Silencing Gal1 expression in regulatory T cells reduced their
      ability to suppress CD7+ (but not CD7-) responder T cells. Additionally, the
      proportions of CD43+ and CD45+ responder T cells were higher in healthy controls
      than in acute rejection transplant patients. CD43 co-expression (but not CD45 co
      expression) on CD7+ responder T cells promoted their apoptosis in a Gal1
      dependent manner. In sum, dysfunctional immunoregulation in liver allograft
      rejection patients can be partly attributed to reduced regulatory T-cell Gal1
      expression and reduced responder T-cell CD7 expression. Responder T-cell CD43
      downregulation in acute rejection patients may further contribute to reduced
      responder T-cell responsiveness to regulatory T-cell control.

PMID- 29463786
TI  - GRK5 functions as an oncogenic factor in non-small-cell lung cancer.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide, and non
      small-cell lung cancer (NSCLC) accounts for about 80% of all cases, which is the
      major subgroup of lung cancer. G protein-coupled receptor kinase 5 (GRK5) has
      been demonstrated to play pivotal roles in both development and progression of
      several pathological conditions including cancer. Here, we found that GRK5
      expression was significantly increased in 539 NSCLC cancerous tissues than that
      in 99 normal non-cancerous tissues by immunohistochemistry analysis; we also
      showed intensive higher positive staining percentage in female and adenocarcinoma
      (ADC) NSCLC patients than that in male and squamous cell carcinoma (SCC)
      patients, respectively. In addition, GRK5 high expression NSCLC patients had a
      worse overall survival rate than the low expression patients. We provided
      evidence showing that both the mRNA and protein expression levels of GRK5 were
      increased in NSCLC cancerous cell lines (GLC-82, SPC-A-1, H520, H838, H358, A549,
      and H1299) comparing with that in normal human bronchial epithelium cell line
      (BEAS-2B), and identified many GRK5 mutations in NSCLC cancerous tissues. In
      addition, we found that depletion of GRK5 inhibited NSCLC cancerous cell
      proliferation, migration in vitro, and xenograft tumor formation in vivo.
      Furthermore, GRK5 knockdown promoted cell cycle arrest at G2/M phase and induced
      cellular apoptosis. In summary, our data reveal an oncogenic role of GRK5 in
      NSCLC progression, indicating that GRK5 could be used as a new therapeutic target
      in future.

PMID- 29463787
TI  - Committed sea-level rise under the Paris Agreement and the legacy of delayed
      mitigation action.
AB  - Sea-level rise is a major consequence of climate change that will continue long
      after emissions of greenhouse gases have stopped. The 2015 Paris Agreement aims
      at reducing climate-related risks by reducing greenhouse gas emissions to net
      zero and limiting global-mean temperature increase. Here we quantify the effect
      of these constraints on global sea-level rise until 2300, including Antarctic ice
      sheet instabilities. We estimate median sea-level rise between 0.7 and 1.2 m, if
      net-zero greenhouse gas emissions are sustained until 2300, varying with the
      pathway of emissions during this century. Temperature stabilization below 2 
      degrees C is insufficient to hold median sea-level rise until 2300 below 1.5 m.
      We find that each 5-year delay in near-term peaking of CO2 emissions increases
      median year 2300 sea-level rise estimates by ca. 0.2 m, and extreme sea-level
      rise estimates at the 95th percentile by up to 1 m. Our results underline the
      importance of near-term mitigation action for limiting long-term sea-level rise
      risks.

PMID- 29463788
TI  - Diverse genetic error modes constrain large-scale bio-based production.
AB  - A transition toward sustainable bio-based chemical production is important for
      green growth. However, productivity and yield frequently decrease as large-scale
      microbial fermentation progresses, commonly ascribed to phenotypic variation.
      Yet, given the high metabolic burden and toxicities, evolutionary processes may
      also constrain bio-based production. We experimentally simulate large-scale
      fermentation with mevalonic acid-producing Escherichia coli. By tracking growth
      rate and production, we uncover how populations fully sacrifice production to
      gain fitness within 70 generations. Using ultra-deep (>1000*) time-lapse
      sequencing of the pathway populations, we identify multiple recurring intra
      pathway genetic error modes. This genetic heterogeneity is only detected using
      deep-sequencing and new population-level bioinformatics, suggesting that the
      problem is underestimated. A quantitative model explains the population dynamics
      based on enrichment of spontaneous mutant cells. We validate our model by tuning
      production load and escape rate of the production host and apply multiple
      orthogonal strategies for postponing genetically driven production declines.

PMID- 29463789
TI  - Extraction condition optimization and effects of drying methods on
      physicochemical properties and antioxidant activities of polysaccharides from
      Astragalus cicer L.
AB  - Response surface methodology (RSM) including three variables was performed to
      optimize the extraction parameters of Astragalus cicer L. polysaccharides (ACPs).
      The influence of different drying techniques on the physicochemical properties
      and antioxidant abilities of ACPs were evaluated. The ACPs were dried with hot
      air (HD), vacuum (VD) and freeze drying (FD) methods. The optimal conditions for
      ACPs extraction were as follows: water to raw material ratio of 25 mL/g,
      extraction time of 61 min and temperature of 75  degrees C. Under these
      parameters, an ACPs yield of 10.97% was obtained. HPLC analysis showed that the
      monosaccharide compositions of the three ACPs dried with HD, VD or FD techniques
      were identical. The three ACPs exhibited antioxidant abilities in a concentration
      dependent manner. ACPs dried with the FD method (FD-ACPs) had the best
      antioxidant activities, which might be related to their smaller molecular weight
      and higher uronic acid content. At the determined concentration of 1 mg/mL, the
      ferric reducing power, and DPPH and ABTS free radical scavenging capacities of FD
      ACPs were 0.762, 75.30% and 99.21%, respectively. Therefore, FD was a good choice
      for the drying of Astragalus cicer L. polysaccharides.

PMID- 29463790
TI  - Contribution of TMEM16F to pyroptotic cell death.
AB  - Pyroptosis is a highly inflammatory form of programmed cell death that is caused
      by infection with intracellular pathogens and activation of canonical or
      noncanonical inflammasomes. The purinergic receptor P2X7 is activated by the
      noncanonical inflammasome and contributes essentially to pyroptotic cell death.
      The Ca2+ activated phospholipid scramblase and ion channel TMEM16F has been shown
      earlier to control cellular effects downstream of purinergic P2X7 receptors that
      ultimately lead to cell death. As pyroptotic cell death is accompanied by an
      increases in intracellular Ca2+, we asked whether TMEM16F is activated during
      pyroptosis. The N-terminal cleavage product of gasdermin D (GD-N) is an
      executioner of pyroptosis by forming large plasma membrane pores. Expression of
      GD-N enhanced basal Ca2+ levels and induced cell death. We observed that GD-N
      induced cell death in HEK293 and HAP1 cells, which was depending on expression of
      endogenous TMEM16F. GD-N activated large whole cell currents that were suppressed
      by knockdown or inhibition of TMEM16F. The results suggest that whole cell
      currents induced by the pore forming domain of gasdermin-D, are at least in part
      due to activation of TMEM16F. Knockdown of other TMEM16 paralogues expressed in
      HAP1 cells suggest TMEM16F as a crucial element during pyroptosis and excluded a
      role of other TMEM16 proteins. Thus TMEM16F supports pyroptosis and other forms
      of inflammatory cell death such as ferroptosis. Its potent inhibition by tannic
      acid may be part of the anti-inflammatory effects of flavonoids.

PMID- 29463791
TI  - The interactome and spatial redistribution feature of Ca2+ receptor protein
      calmodulin reveals a novel role in invadopodia-mediated invasion.
AB  - Numerous studies have shown that calmodulin (CaM) is a major regulator of calcium
      dependent signaling, which regulates cell proliferation, programmed cell death,
      and autophagy in cancer. However, limited information is available on mechanisms
      underlying the effect of CaM on the invasive property of glioblastoma multiforme
      (GBM) cells, especially with respect to invadopodia formation. In this study, we
      find that CaM serves as a prognostic factor for GBM, and it is strongly
      associated with the invasive nature of this tumor. Results of preliminary
      experiments indicated that CaM concentration was significantly correlated with
      the invasive capacity of and invadopodia formation by different GBM cell lines.
      CaM inhibition via a small hairpin RNA or a pharmacological inhibitor
      significantly disrupted invadopodia formation and MMP activity and downregulated
      vimentin expression. Moreover, CaM knockdown exerted a strong anti-invasive
      effect on GBM in vivo. Interestingly, epidermal growth factor treatment promoted
      CaM redistribution from the nucleus to the cytoplasm, eventually activating
      invadopodia-associated proteins by binding to them via their cytosolic-binding
      sites. Moreover, CaM inhibition suppressed the activation of invadopodia
      associated proteins. Thus, our findings provide a novel therapeutic strategy to
      impede GBM invasion by inhibiting invadopodia formation, and shed light on the
      spatial organization of CaM signals during GBM invasion.

PMID- 29463792
TI  - Glutamate-induced and NMDA receptor-mediated neurodegeneration entails P2Y1
      receptor activation.
AB  - Despite the characteristic etiologies and phenotypes, different brain disorders
      rely on common pathogenic events. Glutamate-induced neurotoxicity is a pathogenic
      event shared by different brain disorders. Another event occurring in different
      brain pathological conditions is the increase of the extracellular ATP levels,
      which is now recognized as a danger and harmful signal in the brain, as heralded
      by the ability of P2 receptors (P2Rs) to affect a wide range of brain disorders.
      Yet, how ATP and P2R contribute to neurodegeneration remains poorly defined. For
      that purpose, we now examined the contribution of extracellular ATP and P2Rs to
      glutamate-induced neurodegeneration. We found both in vitro and in vivo that
      ATP/ADP through the activation of P2Y1R contributes to glutamate-induced neuronal
      death in the rat hippocampus. We found in cultured rat hippocampal neurons that
      the exposure to glutamate (100 uM) for 30 min triggers a sustained increase of
      extracellular ATP levels, which contributes to NMDA receptor (NMDAR)-mediated
      hippocampal neuronal death through the activation of P2Y1R. We also determined
      that P2Y1R is involved in excitotoxicity in vivo as the blockade of P2Y1R
      significantly attenuated rat hippocampal neuronal death upon the systemic
      administration of kainic acid or upon the intrahippocampal injection of
      quinolinic acid. This contribution of P2Y1R fades with increasing intensity of
      excitotoxic conditions, which indicates that P2Y1R is not contributing directly
      to neurodegeneration, rather behaving as a catalyst decreasing the threshold from
      which glutamate becomes neurotoxic. Moreover, we unraveled that such
      excitotoxicity process began with an early synaptotoxicity that was also
      prevented/attenuated by the antagonism of P2Y1R, both in vitro and in vivo. This
      should rely on the observed glutamate-induced calpain-mediated axonal
      cytoskeleton damage, most likely favored by a P2Y1R-driven increase of NMDAR
      mediated Ca2+ entry selectively in axons. This may constitute a degenerative
      mechanism shared by different brain diseases, particularly relevant at initial
      pathogenic stages.

PMID- 29463794
TI  - Secondary Phase Interaction at Interfaces of High-Strength Brazed Joints made
      using Liquid Phase Sintered Alumina Ceramics and Ag-Cu-Ti Braze Alloys.
AB  - Alumina-to-alumina brazed joints were formed using 96.0 and 99.7 wt.% Al2O3
      ceramics using 150 um thick Ticusil(r) (68.8Ag-26.7Cu-4.7 wt.% Ti) braze
      preforms. Brazing was conducted in a vacuum of 1 * 10-5 mbar at 850  degrees C
      for 10 minutes. Joint strengths were evaluated using four-point bend testing and
      were compared to the monolithic flexural strengths of standard alumina test bars
      according to ASTM C1161-13. Brazed joints made using 96.0 wt.% Al2O3 consistently
      outperformed brazed joints made using 99.7 wt.% Al2O3, despite similarities in
      both the flexural strengths of the standard alumina test bars and the
      microstructures of brazed joints. Secondary phase interaction led to the
      formation of Ti5Si3 reaction products at locations where the triple pocket grain
      boundaries of the 96.0 wt.% Al2O3 surface intersected the Ti-rich reaction
      layers. It is proposed that due to this interaction, brazed joints made using
      96.0 wt.% Al2O3, which were relatively cost-effective to produce, achieved higher
      strengths than brazed joints made using 99.7 wt.% Al2O3.

PMID- 29463793
TI  - Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease.
AB  - Polycystic kidney disease (PKD) is a genetic disorder characterized by fluid
      filled cysts in the kidney and liver that ultimately leads to end-stage renal
      disease. Currently there is no globally approved therapy for PKD. The Notch
      signaling pathway regulates cellular processes such as proliferation and de
      differentiation, which are cellular hallmarks of PKD. Thus we hypothesized that
      the Notch pathway plays a critical role in PKD. Evaluation of protein expression
      of Notch signaling components in kidneys of Autosomal Recessive PKD (ARPKD) and
      Autosomal Dominant PKD (ADPKD) mouse models and of ADPKD patients revealed that
      Notch pathway members, particularly Notch3, were consistently upregulated or
      activated in cyst-lining epithelial cells. Notch3 expression correlated with
      rapidly growing cysts and co-localized with the proliferation marker, PCNA.
      Importantly, Notch inhibition significantly decreased forskolin-induced Notch3
      activation and proliferation of primary human ADPKD cells, and significantly
      reduced cyst formation and growth of human ADPKD cells cultured in collagen gels.
      Thus our data indicate that Notch3 is aberrantly activated and facilitates
      epithelial cell proliferation in PKD, and that inhibition of Notch signaling may
      prevent cyst formation and growth.

PMID- 29463795
TI  - The mark of vegetation change on Earth's surface energy balance.
AB  - Changing vegetation cover alters the radiative and non-radiative properties of
      the surface. The result of competing biophysical processes on Earth's surface
      energy balance varies spatially and seasonally, and can lead to warming or
      cooling depending on the specific vegetation change and background climate. Here
      we provide the first data-driven assessment of the potential effect on the full
      surface energy balance of multiple vegetation transitions at global scale. For
      this purpose we developed a novel methodology that is optimized to disentangle
      the effect of mixed vegetation cover on the surface climate. We show that
      perturbations in the surface energy balance generated by vegetation change from
      2000 to 2015 have led to an average increase of 0.23 +/- 0.03  degrees C in local
      surface temperature where those vegetation changes occurred. Vegetation
      transitions behind this warming effect mainly relate to agricultural expansion in
      the tropics, where surface brightening and consequent reduction of net radiation
      does not counter-balance the increase in temperature associated with reduction in
      transpiration. This assessment will help the evaluation of land-based climate
      change mitigation plans.

PMID- 29463796
TI  - Winter Burst of Pristine Kashmir Valley Air.
AB  - The Kashmir Valley in India is one of the world's major tourist attractions and
      perceived as a pristine environment. Long term monitoring of fine particulate
      matter, PM2.5 (particles having aerodynamic diameter of 2.5 MUm or less),
      responsible for deteriorating human health, has been done for the period 2013-14.
      Results indicate that air quality of the capital city Srinagar (34.1 degrees N,
      74.8 degrees E) deteriorates significantly in particular during winter, where
      level of PM2.5 touches a peak value of 348 MUg/m3 against the Indian permissible
      limit of 60 MUg/m3. The emissions due to domestic coal usage are found to be
      1246.4 tons/yr, which accounts for 84% of the total annual emissions. The on-line
      high-resolution weather research and forecasting model with embedded chemistry
      module (WRF-Chem), which accounts for emission inventory developed in this region
      reproduced the seasonal variability reasonably well. Cold temperatures with dry
      conditions along with elevated level of biofuel emissions from domestic sector
      are found to be the major processes responsible for winter period particulate
      pollution. The back trajectories show that westerly winds originating from
      Afghanistan and surrounding areas also contribute to the high PM2.5 levels.

PMID- 29463798
TI  - NDRG2 programs tumor-associated macrophages for tumor support.

PMID- 29463797
TI  - Induction of ER and mitochondrial stress by the alkylphosphocholine erufosine in
      oral squamous cell carcinoma cells.
AB  - Endoplasmic reticulum (ER) plays an essential role in cell function and survival.
      Accumulation of unfolded or misfolded proteins in the lumen of the ER activates
      the unfolded protein response (UPR), resulting in ER stress and subsequent
      apoptosis. The alkylphosphocholine erufosine is a known Akt-mTOR inhibitor in
      oral squamous cell carcinoma (OSCC). In the present study, we evaluate
      erufosine's role to induce ER and mitochondrial stress leading to autophagy,
      apoptosis, and ROS induction. The cellular toxicity of erufosine was determined
      in two OSCC cell lines and gene expression and enrichment analyses were
      performed. A positive enrichment of ER stress upon erufosine exposure was
      observed, which was verified at protein levels for the ER stress sensors and
      their downstream mediators. Knockdown and pharmacological inhibition of the ER
      stress sensors PERK and XBP1 revealed their involvement into erufosine's cellular
      effects, including proliferation, apoptosis, and autophagy induction. Autophagy
      was confirmed by increased acidic vacuoles and LC3-B levels. Upon erufosine
      exposure, calcium influx into the cytoplasm of the two OSCC cell lines was seen.
      Apoptosis was confirmed by nuclear staining, Annexin-V, and immunoblotting of
      caspases. The induction of mitochondrial stress upon erufosine exposure was
      predicted by gene set enrichment analysis (GSEA) and shown by erufosine's effect
      on mitochondrial membrane potential, ATP, and ROS production in OSCC cells. These
      data show that ER and mitochondrial targeting by erufosine represents a new facet
      of its mechanism of action as well as a promising new framework in the treatment
      of head and neck cancers.

PMID- 29463799
TI  - Remodeling of the Candida glabrata cell wall in the gastrointestinal tract
      affects the gut microbiota and the immune response.
AB  - The gastrointestinal (GI) microbiota acts a natural barrier to the proliferation
      of opportunistic pathogens. Candida glabrata is an opportunistic yeast pathogen
      that has adapted to colonize all segments of the human GI tract. We observed an
      increase in Escherichia coli, Enterococcus faecalis, and Bacteroides vulgatus
      populations, and a decrease in Lactobacillus johnsonii, Bacteroides
      thetaiotaomicron, and Bifidobacterium animalis in mice with DSS-induced colitis.
      This reduction was more pronounced for L. johnsonii during C. glabrata
      overgrowth. In addition, C. glabrata overgrowth increased mouse mortality and
      inflammatory parameters, and modulated the expression of intestinal receptors and
      signaling pathways. The C. glabrata cell wall underwent various changes during
      the course of C. glabrata colonization, and showed a significant increase in
      chitin. C. glabrata deficient in chitin synthase-3 induced fewer inflammatory
      parameters than the parental strain during intestinal inflammation. Oral
      administration of chitin attenuated the impact of colitis, and reduced the number
      of aerobic bacteria and C. glabrata overgrowth, while chitinase-3-like protein-1
      increased. This study provides evidence that inflammation of the gut alters the
      microbial balance and leads to C. glabrata cell wall remodeling through an
      increase in chitin, which is involved in promoting persistence of C. glabrata in
      the gut.

PMID- 29463800
TI  - Mapping the dispersion of water wave channels.
AB  - Large classes of electronic, photonic, and acoustic crystals and quasi-crystals
      have been predicted to support topological wave-modes. Some of these modes are
      stabilized by certain symmetries but others occur as pure wave phenomena, hence
      they can be observed in many other media that support wave propagation. Surface
      water-waves are mechanical in nature but very different from the elastic waves,
      hence they can provide a new platform for studying topological wave-modes.
      Motivated by this perspective, we report theoretical and experimental
      characterizations of water-wave crystals obtained by periodic patterning of the
      water surface. In particular, we demonstrate the band structure of the spectra
      and existence of spectral gaps.

PMID- 29463801
TI  - Compensatory increases in tear volume and mucin levels associated with meibomian
      gland dysfunction caused by stearoyl-CoA desaturase-1 deficiency.
AB  - The stearoyl-CoA desaturase (SCD) family of enzymes catalyzes monounsaturated
      fatty acid synthesis by inserting a cis double bond at the Delta9 position of
      saturated fatty acids. Disruption of these enzymes has been reported to induce a
      severe dry skin phenotype. Since lipid abnormalities in the meibomian glands have
      been associated with dry eye, we analyzed selected eye tissues contributing to
      tear volume and composition in genetically SCD-1-deficient mice (SCD-1 KO),
      including the lacrimal glands and conjunctiva. Previous histopathological
      analysis had revealed atrophy and loss of meibomian glands; taken together with
      the increased goblet cell and MUC5AC expression in the conjunctiva reported here,
      these findings suggest that the tear volume and mucin levels secreted are
      enhanced in the absence of lipid secretion as a compensatory mechanism. The
      expression of lipid metabolism genes in lacrimal glands was decreased in SCD1 KO
      mice. Thus, these results provide new pathophysiological mechanisms to pursue
      with regard to meibomian gland dysfunction. In addition, lack of SCD-1 causes a
      compensatory increase in the tear volume and mucin levels associated with changes
      in expression of lipid metabolism genes. These results may be useful as a new
      concept for dry eye treatment strategies.

PMID- 29463803
TI  - ALCAM+ stromal cells: role in giant cell tumor of bone progression.
AB  - Giant cell tumor of bone(GCTB) is a special benign tumor with variable
      aggressiveness and recurrence rate. Increasing evidences suggest that a subset of
      cells called cancer stem cells (CSCs) are present as cancer-initiating cells in a
      range of malignant tumors. However, the role of CSCs in benign tumor such as GCTB
      remains unknown, and the connection between the presence of CSCs and biological
      characteristics of GCTB is unclear. To investigate this issue, we screened a
      panel of markers of normal stem cells and CSCs and found ALCAM+ stromal cells
      possessed characteristics of stem-like cells. Subsequently a series of
      experiments such cell proliferation, migration and invasion assays were performed
      to investigate the biological characteristics of ALCAM+ stromal cells in vivo and
      in vitro. The clinical significance of ALCAM expression were further evaluated
      using Kaplan-Meier analyses. The ALCAM+ GCTB cells showed the stem cell
      properties of self renewal and had the capacity to differentiate in vitro. The
      ALCAM+ GCTB cells showed increased resistance for chemotherapy- or radiation
      induced cell death. ALCAM knockdown reduced stem/progenitor characteristics in
      GCTB Cells. Furthermore, ALCAM expression was associated with outcome in GCTB
      patients. Our work demonstrates for the first time ALCAM+ tumorigenic sub
      population within stromal GCTB cells and may represent a potential therapeutic
      target in aggressive and recurrent GCTBs.

PMID- 29463804
TI  - The optimal movement patterns for mating encounters with sexually asymmetric
      detection ranges.
AB  - Animals have evolved various sex-specific characteristics to improve the
      efficiency of mating encounters. One is the sex-specific attracting signal.
      Signal receivers perform a combination of random search and navigation before and
      after signal detections. On the other hand, signal senders can also modify their
      movement patterns to optimize their encounter rates, which invokes a reverse side
      of random search problems that asks for the most efficient movement patterns of
      signal senders to be found by signal receivers. In this study, we focused on
      visual and auditory signals in particular, and quantified the efficiency of
      mating encounters of individual animals performing a Levy walk, a special class
      of random walk, with a variety of speeds before signal detection. We found that
      signal senders should move more slowly and/or less diffusively than receivers to
      improve mating encounters. The optimal movement patterns of senders ranged from
      relatively slow to stationary ones depending on the density of individuals, the
      effective range of signals, and the ability of receivers to locate senders. By
      focusing on the optimal movement patterns of individuals that are often assumed
      to be given targets, the present study provides insights into strategies of
      effective attraction beyond the case of mate search.

PMID- 29463802
TI  - Clonal dynamics towards the development of venetoclax resistance in chronic
      lymphocytic leukemia.
AB  - Deciphering the evolution of cancer cells under therapeutic pressure is a crucial
      step to understand the mechanisms that lead to treatment resistance. To this end,
      we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia
      (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax.
      Here, we report recurrent mutations in BTG1 (2 patients) and homozygous deletions
      affecting CDKN2A/B (3 patients) that developed during treatment, as well as a
      mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might
      pinpoint molecular aberrations offering structures for further therapeutic
      interventions.

PMID- 29463805
TI  - Ceramide-induced BOK promotes mitochondrial fission in preeclampsia.
AB  - Mitochondria are in a constant balance of fusing and dividing in response to
      cellular cues. Fusion creates healthy mitochondria, whereas fission results in
      removal of non-functional organelles. Changes in mitochondrial dynamics typify
      several human diseases. However, the contribution of mitochondrial dynamics to
      preeclampsia, a hypertensive disorder of pregnancy characterized by placental
      cell autophagy and death, remains unknown. Herein, we show that the mitochondrial
      dynamic balance in preeclamptic placentae is tilted toward fission (increased
      DRP1 expression/activation and decreased OPA1 expression). Increased
      phosphorylation of DRP1 (p-DRP1) in mitochondrial isolates from preeclamptic
      placentae and transmission electron microscopy corroborated augmented
      mitochondrial fragmentation in cytotrophoblast cells of PE placentae. Increased
      fission was accompanied by build-up of ceramides (CERs) in mitochondria from
      preeclamptic placentae relative to controls. Treatment of human choriocarcinoma
      JEG3 cells and primary isolated cytrophoblast cells with CER 16:0 enhanced
      mitochondrial fission. Loss- and gain-of-function experiments showed that Bcl-2
      member BOK, whose expression is increased by CER, positively regulated p
      DRP1/DRP1 and MFN2 expression, and localized mitochondrial fission events to the
      ER/MAM compartments. We also identified that the BH3 and transmembrane domains of
      BOK were vital for BOK regulation of fission. Moreover, we found that full-length
      PTEN-induced putative kinase 1 (PINK1) and Parkin, were elevated in mitochondria
      from PE placentae, implicating mitophagy as the process that degrades excess
      mitochondria fragments produced from CER/BOK-induced fission in preeclampsia. In
      summary, our study uncovered a novel CER/BOK-induced regulation of mitochondrial
      fission and its functional consequence for heightened trophoblast cell autophagy
      in preeclampsia.

PMID- 29463806
TI  - Neural substrates of norm compliance in perceptual decisions.
AB  - Societal norms exert a powerful influence on our decisions. Behaviours motivated
      by norms, however, do not always concur with the responses mandated by decision
      relevant information potentially generating a conflict. To probe the interplay
      between normative and informational influences, we examined how prosocial norms
      impact on perceptual decisions subjects made in the context of a simultaneous
      presentation of social information. Participants displayed a bias in their
      perceptual decisions towards that mandated by social information. However,
      normative prescriptions modulated this bias bi-directionally depending on whether
      norms mandated a decision in accord or contrary to the contextual social
      information. At a neural level, the addition of a norms increased activity in
      prefrontal cortex and modulated functional connectivity between prefrontal and
      parietal areas. The bi-directional effect of our norms was captured by
      differential activations when participants decided against the social
      information. When norms indicated a decision in line with social information, non
      compliance modulated lateral prefrontal cortex activity. By contrast, when norms
      mandated a decision against social information norm compliance increased activity
      in the anterior cingulate cortex. Hence, social norms changed the balance between
      a reliance on perceptual and social information by modulating brain activity in
      regions associated with response inhibition and conflict monitoring.

PMID- 29463807
TI  - Passively mode-locked interband cascade optical frequency combs.
AB  - Since their inception, optical frequency combs have transformed a broad range of
      technical and scientific disciplines, spanning time keeping to navigation.
      Recently, dual comb spectroscopy has emerged as an attractive alternative to
      traditional Fourier transform spectroscopy, since it offers higher measurement
      sensitivity in a fraction of the time. Midwave infrared (mid-IR) frequency combs
      are especially promising as an effective means for probing the strong fundamental
      absorption lines of numerous chemical and biological agents. Mid-IR combs have
      been realized via frequency down-conversion of a near-IR comb, by optical pumping
      of a micro-resonator, and beyond 7 MUm by four-wave mixing in a quantum cascade
      laser. In this work, we demonstrate an electrically-driven frequency comb source
      that spans more than 1 THz of bandwidth centered near 3.6 MUm. This is achieved
      by passively mode-locking an interband cascade laser (ICL) with gain and
      saturable absorber sections monolithically integrated on the same chip. The new
      source will significantly enhance the capabilities of mid-IR multi-heterodyne
      frequency comb spectroscopy systems.

PMID- 29463808
TI  - A novel heterogeneous network-based method for drug response prediction in cancer
      cell lines.
AB  - An enduring challenge in personalized medicine lies in selecting a suitable drug
      for each individual patient. Here we concentrate on predicting drug responses
      based on a cohort of genomic, chemical structure, and target information.
      Therefore, a recently study such as GDSC has provided an unprecedented
      opportunity to infer the potential relationships between cell line and drug.
      While existing approach rely primarily on regression, classification or multiple
      kernel learning to predict drug responses. Synthetic approach indicates drug
      target and protein-protein interaction could have the potential to improve the
      prediction performance of drug response. In this study, we propose a novel
      heterogeneous network-based method, named as HNMDRP, to accurately predict cell
      line-drug associations through incorporating heterogeneity relationship among
      cell line, drug and target. Compared to previous study, HNMDRP can make good use
      of above heterogeneous information to predict drug responses. The validity of our
      method is verified not only by plotting the ROC curve, but also by predicting
      novel cell line-drug sensitive associations which have dependable literature
      evidences. This allows us possibly to suggest potential sensitive associations
      among cell lines and drugs. Matlab and R codes of HNMDRP can be found at
      following https://github.com/USTC-HIlab/HNMDRP .

PMID- 29463809
TI  - Delivery of exogenous mitochondria via centrifugation enhances cellular metabolic
      function.
AB  - Mitochondria are essential organelles involved in the maintenance of cell growth
      and function, and have been investigated as therapeutic targets in various
      diseases. Recent studies have demonstrated that direct mitochondrial transfer can
      restore cellular functions of cells with inherited or acquired mitochondrial
      dysfunction. However, previous mitochondrial transfer methods are inefficient and
      time-consuming. Here, we developed a simple and easy mitochondrial transfer
      protocol using centrifugation, which can be applied to any cell type. By our
      simple centrifugation method, we found that the isolated mitochondria could be
      successfully transferred into target cells, including mitochondrial DNA-deleted
      Rho0 cells and dexamethasone-treated atrophic muscle cells. We found that
      mitochondrial transfer normalised ATP production, mitochondrial membrane
      potential, mitochondrial reactive oxygen species level, and the oxygen
      consumption rate of the target cells. Furthermore, delivery of intact
      mitochondria blocked the AMPK/FoxO3/Atrogene pathway underlying muscle atrophy in
      atrophic muscle cells. Taken together, this simple and rapid mitochondrial
      transfer method can be used to treat mitochondrial dysfunction-related diseases.

PMID- 29463810
TI  - Dynamical complexity and computation in recurrent neural networks beyond their
      fixed point.
AB  - Spontaneous activity found in neural networks usually results in a reduction of
      computational performance. As a consequence, artificial neural networks are often
      operated at the edge of chaos, where the network is stable yet highly susceptible
      to input information. Surprisingly, regular spontaneous dynamics in Neural
      Networks beyond their resting state possess a high degree of spatio-temporal
      synchronization, a situation that can also be found in biological neural
      networks. Characterizing information preservation via complexity indices, we show
      how spatial synchronization allows rRNNs to reduce the negative impact of regular
      spontaneous dynamics on their computational performance.

PMID- 29463811
TI  - Consequences of VHL Loss on Global DNA Methylome.
AB  - In clear-cell renal cell carcinoma (ccRCC), loss of von Hippel-Lindau (VHL)
      tumour suppressor gene and reduced oxygen tension promote stabilisation of
      hypoxia-inducible factor (HIF) family of transcription factors, which promote
      changes in the expression of genes that contribute to oncogenesis. Multiple
      studies have demonstrated significant perturbations in DNA methylation in ccRCC
      via largely unclear mechanisms that modify the transcriptional output of tumour
      cells. Here, we show that the methylation status of the CpG dinucleotide within
      the consensus hypoxia-responsive element (HRE) markedly influences the binding of
      HIF and that the loss of VHL results in significant alterations in the DNA
      methylome. Surprisingly, hypoxia, which likewise promotes HIF stabilisation and
      activation, has relatively few effects on global DNA methylation. Gene expression
      analysis of ccRCC patient samples highlighted expression of a group of genes
      whose transcription correlated with methylation changes, including hypoxic
      responsive genes such as VEGF and TGF. These results suggest that the loss of VHL
      alters DNA methylation profile across the genome, commonly associated with and
      contributing to ccRCC progression.

PMID- 29463812
TI  - Metformin Use and Severe Dengue in Diabetic Adults.
AB  - Diabetes mellitus is a risk factor for severe dengue in adults, but few studies
      have examined the association between metformin use and disease severity in
      dengue. In addition to its effect on glucose control, metformin has been
      associated with pleiotropic properties in preclinical studies. Using a cohort of
      laboratory-confirmed adult (>=21 years) dengue patients with diabetes mellitus
      admitted to Tan Tock Seng Hospital, we conducted a retrospective cohort study
      involving 131 (58.7%) metformin users and 92 (41.3%) non-users. Dengue severity
      was categorized as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS)
      in World Health Organization (WHO) 1997 criteria and severe dengue (SD) in WHO
      2009 criteria. Multivariable Poisson regression with robust error variance was
      used to estimate risk ratio (RR). Compared with non-use, metformin use was
      associated with a decreased risk of developing severe dengue (adjusted risk ratio
      [aRR] = 0.60, 95% confidence interval [CI]: 0.37-0.98, P = 0.04). Additionally,
      there was an inverse dose-response relationship (aRR = 0.69, 95% CI: 0.49-0.98, P
      = 0.04) with dengue severity as classified by WHO 2009 criteria. Use of
      metformin, however, was not associated with dengue severity based on WHO 1997
      criteria; and no dose-response relationship was noted. Our results suggest
      metformin use could attenuate disease severity in dengue-infected diabetes
      mellitus individuals.

PMID- 29463813
TI  - Oligomeric proanthocyanidins (OPCs) target cancer stem-like cells and suppress
      tumor organoid formation in colorectal cancer.
AB  - Proanthocyanidins are a heterogeneous group of flavan-3-ol or flavan-3,4-diol
      oligomers present in various fruits and vegetables. In particular, the smaller
      oligomeric subset of proanthocyanidins, termed the oligomeric proanthocyanidins
      (OPCs) appear to have potent anti-tumorigenic properties, but the underlying
      mechanisms for their effectiveness remain unclear. Herein, we utilized a series
      of in vitro, in vivo and patient-derived organoid approaches to systematically
      investigate the chemoprotective role of OPCs in colorectal cancer. OPCs exerted
      anti-tumorigenic effects through inhibition of cellular proliferation, and
      induced apoptosis and cell cycle arrest. Intriguingly, OPCs suppressed spheroid
      derived cancer stem-like cell formation and decreased the expression of
      intestinal cancer stem cell markers including LGR5, CD44 and CD133.
      Mechanistically, RNA-sequencing results confirmed that OPCs prominently
      interfered with developmental and self-renewal pathways and identified several
      self-renewal associated oncogenes targeted by OPCs. Furthermore, OPCs inhibited
      Hippo pathway through downregulation of its key transcriptional regulators, YAP
      and TAZ. Finally, we confirmed anti-tumorigenic effects of OPCs using multiple
      xenograft experiments and recapitulated its protective effects using patient
      derived colorectal tumor organoids. Collectively, we have comprehensively
      assessed anti-tumorigenic properties of OPCs and our data throws light on
      previously unrecognized chemopreventive mechanisms of OPCs highlighting its
      therapeutic potential.

PMID- 29463815
TI  - Photonic Generation of Triangular-shaped Waveform Based on External Modulation.
AB  - We present a novel approach for triangular-shaped waveform generation by applying
      optical single sideband (OSSB) modulation and optical carrier suppression (OCS)
      modulation to an input signal. Firstly, an OSSB modulated signal consists of an
      optical carrier and +1st-order sideband, is initially generated with a dual-drive
      Mach-Zehnder modulator (DD-MZM1) driven by a quadruple frequency RF signal. By
      tuning the amplitude of the RF signal and the bias of the DD-MZM1, the power
      ratio between the carrier and the +1st-order sideband is controlled as 19 dB.
      These two components are then transmitted to a DD-MZM2 which is driven by a
      fundamental frequency. After OCS modulation, four sidebands are existed in
      optical spectra of the modulated signal. By utilizing a fiber Bragg grating (FBG)
      to remove the undesired sideband, an output signal that features a triangular
      shaped waveform is finally achieved.

PMID- 29463814
TI  - LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during
      late mitosis.
AB  - Faithful chromosome segregation and genome maintenance requires the removal of
      all DNA bridges that physically link chromosomes before cells divide. Using C.
      elegans embryos we show that the LEM-3/Ankle1 nuclease defines a previously
      undescribed genome integrity mechanism by processing DNA bridges right before
      cells divide. LEM-3 acts at the midbody, the structure where abscission occurs at
      the end of cytokinesis. LEM-3 localization depends on factors needed for midbody
      assembly, and LEM-3 accumulation is increased and prolonged when chromatin
      bridges are trapped at the cleavage plane. LEM-3 locally processes chromatin
      bridges that arise from incomplete DNA replication, unresolved recombination
      intermediates, or the perturbance of chromosome structure. Proper LEM-3 midbody
      localization and function is regulated by AIR-2/Aurora B kinase. Strikingly, LEM
      3 acts cooperatively with the BRC-1/BRCA1 homologous recombination factor to
      promote genome integrity. These findings provide a molecular basis for the
      suspected role of the LEM-3 orthologue Ankle1 in human breast cancer.

PMID- 29463816
TI  - Social Observation Increases Functional Segregation between MPFC Subregions
      Predicting Prosocial Consumer Decisions.
AB  - Although it is now well documented that observation by others can be a powerful
      elicitor of prosocial behaviour, the underlying neural mechanism is yet to be
      explored. In the present fMRI study, we replicated the previously reported
      observer effect in ethical consumption, in that participants were more likely to
      purchase social products that are sold to support people in need than non-social
      products when being observed by others. fMRI data revealed that the anterior
      cingulate cortex (ACC) and the dorsomedial prefrontal cortex (dmPFC) encoded
      subject-specific value parameters of purchase decisions for social and non-social
      products, respectively, under social observation. The ACC showed strong
      functional coupling with the amygdala and the anterior insula when participants
      in the observation condition were making purchases of social versus non-social
      products. Finally, ventromedial prefrontal cortex (vmPFC) activity predicted
      faster reaction time and increased prosocial behavior during decisions to
      purchase social versus non-social products, regardless of social observation. The
      present findings suggest that subregions of the mPFC, namely the dmPFC, ACC, and
      vmPFC, are hierarchically organized to encode different levels of decision values
      from the value of context-sensitive reputation to that of internalized
      prosociality.

PMID- 29463817
TI  - Difficulties with tunneling of the cuffed catheter: a single-centre experience.
AB  - Tunneling of the cuffed catheter for hemodialysis is an important part of
      insertion procedure with faulty techniques being the cause of catheter
      dysfunctions. We retrospectively analyzed 737 double-lumen cuffed catheter
      procedures between 2008 and 2015 in patients aged 60 +/- 15years, requiring renal
      replacement therapy. Complications of tunneling included kinking, bleeding and
      other problems. In 20 of 737 (2.7%) procedures, the catheter kinked, which was
      observed in 7.7% of silicone and 0.6% of polyurethane catheters. Repositioning
      was attempted in 4, but was successful in only 2 cases. Catheter exchange was
      necessary in 16 cases, but the function was adequate in 2 cases, despite
      radiological signs of kinking. In 6 cases (1 patient with diabetes, 2 with chest
      anatomy changes and medical devices, 2 with systemic sclerosis and 1 with greatly
      enlarged superficial jugular veins) we faced particular difficulties requiring an
      individual solution by tunneling; these are described in detail. The cumulative
      catheter patency rate were 69%, 52% and 37% at 3, 6 and 12 months, respectively.
      In conclusion, the most frequent complication of tunneling was kinking, usually
      necessitating catheter exchange. The silicon catheter kinked more often than the
      polyurethane one. An individual approach is sometimes needed by patients with
      diabetes and anatomical changes of the chest.

PMID- 29463818
TI  - Changed frontal pole gene expression suggest altered interplay between
      neurotransmitter, developmental, and inflammatory pathways in schizophrenia.
AB  - Schizophrenia (Sz) probably occurs after genetically susceptible individuals
      encounter a deleterious environmental factor that triggers epigenetic mechanisms
      to change CNS gene expression. To determine if omnibus changes in CNS gene
      expression are present in Sz, we compared mRNA levels in the frontal pole
      (Brodmann's area (BA) 10), the dorsolateral prefrontal cortex (BA 9) and
      cingulate cortex (BA 33) from 15 subjects with Sz and 15 controls using the
      AffymetrixTM Human Exon 1.0 ST Array. Differences in mRNA levels (+/->=20%; p <
      0.01) were identified (JMP Genomics 5.1) and used to predict pathways and gene x
      gene interactions that would be affected by the changes in gene expression using
      Ingenuity Pathway Analysis. There was significant variation in mRNA levels with
      diagnoses for 566 genes in BA 10, 65 genes in BA 9 and 40 genes in BA 33. In Sz,
      there was an over-representation of genes with changed expression involved in
      inflammation and development in BA 10, cell morphology in BA 9 and amino acid
      metabolism and small molecule biochemistry in BA 33. Using 94 genes with altered
      levels of expression in BA 10 from subjects with Sz, it was possible to construct
      an interactome of proven direct gene x gene interactions that was enriched for
      genes in inflammatory, developmental, oestrogen, serotonergic, cholinergic and
      NRG1 regulated pathways. Our data shows complex, regionally specific changes in
      cortical gene expression in Sz that are predicted to affect homeostasis between
      biochemical pathways already proposed to be important in the pathophysiology of
      the disorder.

PMID- 29463819
TI  - 3D printed water-soluble scaffolds for rapid production of PDMS micro-fluidic
      flow chambers.
AB  - We report a novel method for fabrication of three-dimensional (3D) biocompatible
      micro-fluidic flow chambers in polydimethylsiloxane (PDMS) by 3D-printing water
      soluble polyvinyl alcohol (PVA) filaments as master scaffolds. The scaffolds are
      first embedded in the PDMS and later residue-free dissolved in water leaving an
      inscription of the scaffolds in the hardened PDMS. We demonstrate the strength of
      our method using a regular, cheap 3D printer, and evaluate the inscription
      process and the channels micro-fluidic properties using image analysis and
      digital holographic microscopy. Furthermore, we provide a protocol that allows
      for direct printing on coverslips and we show that flow chambers with a channel
      cross section down to 40 MUm * 300 MUm can be realized within 60 min. These flow
      channels are perfectly transparent, biocompatible and can be used for microscopic
      applications without further treatment. Our proposed protocols facilitate an
      easy, fast and adaptable production of micro-fluidic channel designs that are
      cost-effective, do not require specialized training and can be used for a variety
      of cell and bacterial assays. To help readers reproduce our micro-fluidic
      devices, we provide: full preparation protocols, 3D-printing CAD files for
      channel scaffolds and our custom-made molding device, 3D printer build-plate
      leveling instructions, and G-code.

PMID- 29463820
TI  - Correlation of 360-degree Surface Mapping In Vivo Bioluminescence with Multi
      Spectral Optoacoustic Tomography in Human Xenograft Tumor Models.
AB  - Pre-clinical monitoring of tumor growth and identification of distal metastasis
      requires a balance between accuracy and expediency. Bioluminescence imaging (BLI)
      is often used to track tumor growth but is primarily limited to planar 2
      dimensional (2D) imaging. Consistent subject placement within a standard top
      mounted, single-detector small animal imager is vital to reducing variability in
      repeated same-animal measures over time. Here, we describe a method for tracking
      tumor development using a multi-angle BLI and photo-acoustic workflow. We
      correlate serial caliper measurements and 2D BLI to 360 degrees  BLI and photo
      acoustic datasets for the same animals. Full 360 degrees  BLI showed improved
      correlations with both volumes obtained from caliper measurements and photo
      acoustic segmentation, as compared to planar BLI. We also determined segmented
      tumor volumes from photo-acoustic datasets more accurately reflects true excised
      tumors' volumes compared to caliper measurements. Our results demonstrate the
      distinct advantages of both 360 degrees  surface mapping by BLI and photo
      acoustic methodologies for non-invasive tracking of tumor growth in pre-clinical
      academic settings. Furthermore, our design is fully implementable in all top
      mounted, single-detector imagers, thereby providing the opportunity to shift the
      paradigm away from planar BLI into rapid BLI tomography applications.

PMID- 29463822
TI  - True gene-targeting events by CRISPR/Cas-induced DSB repair of the PPO locus with
      an ectopically integrated repair template.
AB  - In recent years, several tools have become available for improved gene-targeting
      (GT) in plants. DNA breaks at specific sites activate local DNA repair and
      recombination, including recombination with ectopic sequences leading to GT.
      Large-scale transformation with the repair template can be avoided by pre
      insertion of the repair template in the genome and liberation by sequence
      specific nucleases (in planta GT procedure). Here, we tested whether release of
      the repair template was required for GT. Plants were transformed with constructs
      encoding a CRISPR/Cas nuclease with a recognition site in the endogenous PPO gene
      and a repair template harboring a 5' truncated PPO gene with two amino acid
      substitutions rendering the enzyme insensitive to the herbicide butafenacil.
      Selection resulted in so-called true GT events, repaired via homologous
      recombination at both ends of the gene and transmitted to the next generation. As
      the template was surrounded by geminiviral LIR sequences, we also tested whether
      replication of the template could be induced by crossing-in an integrated
      geminivirus REP gene. However, we could not find evidence for repair template
      replication by REP and we obtained similar numbers of GT events in these plants.
      Thus, GT is possible without any further processing of the pre-inserted repair
      template.

PMID- 29463821
TI  - Amygdala hyper-connectivity in a mouse model of unpredictable early life stress.
AB  - Childhood maltreatment is associated with a wide range of psychopathologies
      including anxiety that emerge in childhood and in many cases persist in
      adulthood. Increased amygdala activation in response to threat and abnormal
      amygdala connectivity with frontolimbic brain regions, such as the hippocampus
      and the prefrontal cortex, are some of the most consistent findings seen in
      individuals exposed to childhood maltreatment. The underlying mechanisms
      responsible for these changes are difficult to study in humans but can be
      elucidated using animal models of early-life stress. Such studies are especially
      powerful in the mouse where precise control of the genetic background and the
      stress paradigm can be coupled with resting-state fMRI (rsfMRI) to map abnormal
      connectivity in circuits that regulate anxiety. To address this issue we first
      compared the effects of two models of early-life stress, limited bedding (LB) and
      unpredictable postnatal stress (UPS), on anxiety-like behavior in juvenile and
      adult mice. We found that UPS, but not LB, causes a robust increase in anxiety in
      juvenile and adult male mice. Next, we used rsfMRI to compare frontolimbic
      connectivity in control and UPS adult male mice. We found increased amygdala
      prefrontal cortex and amygdala-hippocampus connectivity in UPS. The strength of
      the amygdala-hippocampal and amygdala-prefrontal cortex connectivity was highly
      correlated with anxiety-like behavior in the open-field test and elevated plus
      maze. These findings are the first to link hyperconnectivity in frontolimbic
      circuits and increased anxiety in a mouse model of early-life stress, allowing
      for more mechanistic understanding of parallel findings in humans.

PMID- 29463823
TI  - Thermally Stable, High Performance Transfer Doping of Diamond using Transition
      Metal Oxides.
AB  - We report on optimisation of the environmental stability and high temperature
      operation of surface transfer doping in hydrogen-terminated diamond using MoO3
      and V2O5 surface acceptor layers. In-situ annealing of the hydrogenated diamond
      surface at 400  degrees C was found to be crucial to enhance long-term doping
      stability. High temperature sheet resistance measurements up to 300  degrees C
      were performed to examine doping thermal stability. Exposure of MoO3 and V2O5
      transfer-doped hydrogen-terminated diamond samples up to a temperature of 300 
      degrees C in ambient air showed significant and irreversible loss in surface
      conductivity. Thermal stability was found to improve dramatically however when
      similar thermal treatment was performed in vacuum or in ambient air when the
      oxide layers were encapsulated with a protective layer of hydrogen silsesquioxane
      (HSQ). Inspection of the films by X-ray diffraction revealed greater
      crystallisation of the MoO3 layers following thermal treatment in ambient air
      compared to the V2O5 films which appeared to remain amorphous. These results
      suggest that proper encapsulation and passivation of these oxide materials as
      surface acceptor layers on hydrogen-terminated diamond is essential to maximise
      their environmental and thermal stability.

PMID- 29463824
TI  - Molecular basis of differential nitrogen use efficiencies and nitrogen source
      preferences in contrasting Arabidopsis accessions.
AB  - Natural accessions of Arabidopsis thaliana differ in their growth and
      development, but also vary dramatically in their nitrogen use efficiencies (NUE).
      The molecular basis for these differences has not been addressed yet. Experiments
      with five contrasting accessions grown in hydroponics at different levels of
      inorganic nitrogen confirmed low NUE of Col-0 and higher NUE in Tsu-0. At
      constant external nitrogen supply, higher NUE was based on nitrogen capture,
      rather than utilization of nitrogen for shoot biomass. This changed when a
      limited nitrogen amount was supplied. Nevertheless, the total NUE sequence
      remained similar. Interestingly, the two most contrasting accessions, Col-0 and
      Tsu-0, differed in the capture of single inorganic nitrogen sources, reflected by
      the differential consumption of 15N label from ammonium or nitrate, when supplied
      together. Tsu-0 acquired more nitrate than Col-0, both in roots and shoots. This
      preference was directly correlated with the expression of certain nitrogen uptake
      and assimilation systems in the root. However, early transcriptional responses of
      the root to nitrate deprivation were similar in both accessions, suggesting that
      the sensing of the external lack of nitrate was not different in the more
      nitrogen use efficient accession. Thus, a robust rapid nitrate-deprivation
      signaling exists in both genotypes.

PMID- 29463825
TI  - Nanostructured Polymer Thin Films Fabricated with Brush-based Layer-by-Layer Self
      assembly for Site-selective Construction and Drug release.
AB  - Layer-by-Layer (LbL) self-assembly has been investigated for several decades.
      However, the conventional LbL method has performance problems on the chair-side
      caused by its cumbersome and time-consuming process. Thus, we investigate a new
      LbL self-assembly technique for the fast and high efficient preparation process
      based on the brush. The multilayer films fabricated by simple sequential brushing
      of polyelectrolyte solutions are compared to the classical dipping method. We
      characterize the multilayer films by characteristics such as their morphology and
      thickness, and compare them against those of the classic method by profilometry,
      atomic force microscopy. We prepare multilayer films with biocompatible
      polyelectrolytes, chitosan, and alginate incorporated with a hydrophobic drug
      carrier. For the drug carrier, a poly(ethylene glycol)-block-poly(epsilon
      caprolactone) (PEG-b-PCL) block copolymer is introduced to construct micelles
      containing dexamethasone, which is a well-known osteogenesis-inducing drug. The
      hydrogen bonding behavior between adjacent layers and micelles is investigated by
      Fourier transform infrared spectroscopy. Additionally, we analyze the release
      profiles, degradation profiles and toxicity of the multilayer films for
      biomedical applications. From these results, we can identify the brushing LbL
      method as a reliable and more efficient multilayer film-construction process
      compared to conventional dipping LbL, especially for practical applications in
      dental and clinical situations.

PMID- 29463826
TI  - VPS4 is a dynamic component of the centrosome that regulates centrosome
      localization of gamma-tubulin, centriolar satellite stability and ciliogenesis.
AB  - The hexameric AAA ATPase VPS4 facilitates ESCRT III filament disassembly on
      diverse intracellular membranes. ESCRT III components and VPS4 have been
      localized to the ciliary transition zone and spindle poles and reported to affect
      centrosome duplication and spindle pole stability. How the canonical ESCRT
      pathway could mediate these events is unclear. We studied the association of VPS4
      with centrosomes and found that GFP-VPS4 was a dynamic component of both mother
      and daughter centrioles. A mutant, VPS4EQ, which can't hydrolyze ATP, was less
      dynamic and accumulated at centrosomes. Centrosome localization of the VPS4EQ
      mutant, caused reduced gamma-tubulin levels at centrosomes and consequently
      decreased microtubule growth and altered centrosome positioning. In addition,
      preventing VPS4 ATP hydrolysis nearly eliminated centriolar satellites and paused
      ciliogensis after formation of the ciliary vesicle. Zebrafish embryos injected
      with GFP-VPS4EQ mRNA were less viable, exhibited developmental defects and had
      fewer cilia in Kupffer's vesicle. Surprisingly, ESCRT III proteins seldom
      localized to centrosomes and their depletion did not lead to these phenotypes.
      Our data support an ESCRT III-independent function for VPS4 at the centrosome and
      reveal that this evolutionary conserved AAA ATPase influences diverse centrosome
      functions and, as a result, global cellular architecture and development.

PMID- 29463827
TI  - Long non-coding RNA AC026166.2-001 inhibits cell proliferation and migration in
      laryngeal squamous cell carcinoma by regulating the miR-24-3p/p27 axis.
AB  - Long non-coding RNA (lncRNA) AC026166.2-001 was found to be down-regulated in
      laryngeal squamous cell carcinoma (LSCC) tissues and metastatic neck lymph nodes.
      Decreased AC026166.2-001 was associated with poorer prognosis and may act as a
      novel biomarker for LSCC patients. In this study, AC026166.2-001 was
      overexpressed by a lentivirus vector and down-regulated by a small interfering
      RNA (siRNA). The results of real-time cell analysis (RTCA) and a plate colony
      formation assay showed that AC026166.2-001 inhibited LSCC cell proliferation and
      the clone-forming capacity. Cell cycle distribution and related protein changes
      were measured by flow cytometry. AC026166.2-001 arrested the cell cycle at the G1
      phase and induced apoptosis. In addition, AC026166.2-001 decreased cell migration
      as measured by wound healing assays and transwell migration assays. Moreover,
      luciferase reporter assay and Western blotting results suggested that AC026166.2
      001 acts as a sponge of miR-24-3p and regulates the expression of p27 and cyclin
      D1. The in vivo results showed that AC026166.2-001 significantly suppressed the
      growth of LSCC xenografts and promoted apoptosis. We validated the molecular
      mechanisms underlying AC026166.2-001 in LSCC. This is the first report of
      AC026166.2-001 acting as a tumor suppressor in LSCC by regulating the miR-24
      3p/p27 axis.

PMID- 29463828
TI  - Blood T1* correction increases accuracy of extracellular volume measurements
      using 3T cardiovascular magnetic resonance: Comparison of T1 and T1* maps.
AB  - The goals were to compare the differences between ECVL (extracellular volume
      derived from myocardial T1 and blood T1), ECVc (combination of myocardial T1 and
      blood T1*), and ECVnL (derived from myocardium T1* and blood T1*), and to explore
      the diagnostic accuracy of these factors for discriminating between controls and
      patients. The Modified Look-Locker Inversion Recovery sequence was performed in
      42 subjects to generate both T1 and T1* maps. Native and post-contrast T1 values
      for myocardium and blood pool were obtained, and ECVL, ECVc, and ECVnL were then
      calculated. The global ECVc values were smaller than the ECVL values (0.006,
      2.11%, p < 0.001) and larger than the ECVnL values (0.06, 21.6%, p < 0.001) in
      all participants. The ECVc led to a 4-6% increase in the AUC value and a 24-32%
      reduction in the sample size to differentiate between the controls and other
      patients when compared with the ECVL. Blood T1* correction can improve the
      precision of blood T1 values and can consequently increase the accuracy of the
      extracellular volume fraction measurement. The ECVc can be used to improve
      diagnostic accuracy and reduce the sample size required for a clinical study.

PMID- 29463829
TI  - Patternable and Widely Colour-Tunable Elastomer-Based Electroluminescent Devices.
AB  - We demonstrate wide colour tunability of polydimethylsiloxane-based alternating
      current-driven electroluminescent devices with intrinsically stretchable
      characteristics achieved by simply modulating the electrical frequency. By
      employing both a screen-printed emitting layer and frequency-dependent colour
      tuning of ZnS:Cu-based phosphors, we demonstrate various coloured patterned
      images in a single device. We also show enhanced colour-tuning performance by
      mixing multi-colour phosphors, which results in a broad range of available
      coordinates in colour space. We believe that our demonstrated method could be
      used for manipulating broader colour expression as well as in various
      applications involving stretchable devices.

PMID- 29463830
TI  - Evolving M-protein pattern in patients with smoldering multiple myeloma: impact
      on early progression.
AB  - Smoldering multiple myeloma (SMM) is a biologically heterogeneous, clinically
      defined entity with a variable rate of progression to symptomatic multiple
      myeloma (MM). Reliable markers for progression are critical for the development
      of potential therapeutic interventions. We retrospectively evaluated the
      predictive value of the evolving pattern of serum M-protein among other
      progression risk factors in 206 patients with SMM diagnosed between 1973 and
      2012. Median time from recognition of evolving type to progression into
      symptomatic MM was 1.1 years (95% CI 0.5-2.0) and progression rate at 3 years was
      71%. Development of the evolving type drastically worsened the prognostic
      estimation made at diagnosis for every covariate predictive of progression (serum
      M-protein size, bone marrow plasma cell infiltration, immunoparesis and Mayo
      Clinic risk). On average, the hazard ratio for progression to symptomatic MM
      increased to 5.1 (95% CI 3.4-7.6) after recognition of the evolving type. In
      conclusion, in patients with SMM the evolving pattern accurately predicts the
      risk of early progression to symptomatic disease, thereby allowing the
      identification of ultra-high risk patients who would be candidates for immediate
      therapy.

PMID- 29463831
TI  - Shikonin exerts antitumor activity in Burkitt's lymphoma by inhibiting C-MYC and
      PI3K/AKT/mTOR pathway and acts synergistically with doxorubicin.
AB  - Burkitt's lymphoma (BL) is a highly aggressive malignancy molecularly
      characterized by deregulation of the C-MYC proto-oncogene. Recently, it has been
      confirmed that phosphatidylinositol-3-kinase (PI3K) pathway activation is a
      crucial element in the malignant transformation of the B cells in BL. Despite the
      better outcome of adults with BL treated with high-intensity chemotherapy
      regimens, the overall survival rate for patients older than 60 years remains
      dismal. Shikonin, a natural naphthoquinone derived from Chinese herbal medicine
      plant, has the potential to induce cell death in a series of human cancer. In the
      present study, we investigated the effect and molecular mechanisms of Shikonin in
      treatment with BL. Shikonin suppressed cellular proliferation and induced caspase
      dependent apoptosis in BL cells. Inhibition of C-MYC and suppression of
      PI3K/AKT/mTOR pathway played critical roles in SHK-induced apoptosis in BL both
      in vitro and in vivo. Besides, Shikonin potentiated doxorubicin-induced growth
      inhibition and apoptosis in vitro. Furthermore, the growth of a subcutaneous
      xenograft tumor model of BL was significantly inhibited by shikonin. Importantly,
      we did not find the effect of shikonin on liver function in mice. In summary,
      these data suggest that shikonin may be an encouraging chemotherapeutic agent in
      the clinical treatment of BL.

PMID- 29463832
TI  - Frequency of early vascular aging and associated risk factors among an adult
      population in Latin America: the OPTIMO study.
AB  - The main objective was to estimate the frequency of early vascular aging (EVA) in
      a sample of subjects from Latin America, with emphasis in young adults. We
      included 1416 subjects from 12 countries in Latin America who provided
      information about lifestyle, cardiovascular risk factors (CVRF), and
      anthropometrics. We measured pulse wave velocity (PWV) as a marker of arterial
      stiffness, and blood pressure (BP) using an oscillometric device (Mobil-O-Graph).
      To determine the frequency of EVA, we used multiple linear regression to estimate
      each subject's PWV expected for his/her age and systolic BP, and compared with
      observed values to obtain standardized residuals (z-scores). We defined EVA when
      z-score was >=1.96. Finally, a multivariable logistic regression analysis was
      performed to determine baseline characteristics associated with EVA. Mean age was
      49.9 +/- 15.5 years, male gender was 50.3%. Mean PWV was 7.52 m/s (SD 1.97), mean
      systolic BP was 125.3 mmHg (SD 16.7) and mean diastolic BP was 78.9 mmHg (SD
      12.2). The frequency of EVA was 5.7% in the total population, 9.8% in adults of
      40 years or less and 18.7% in those 30 years or less. In these young adults,
      multiple logistic regression analyses demonstrated that dyslipidemia and
      hypertension showed an independent association with EVA, and smoking a borderline
      association (p  =  0.07). In conclusion, the frequency of EVA in a sample from
      Latin America was around 6%, with higher rates in young adults. These results
      would support the search of CVRF and EVA during early adulthood.

PMID- 29463833
TI  - Associations of NADPH oxidase-related genes with blood pressure changes and
      incident hypertension: The GenSalt Study.
AB  - Previous studies have indicated that reactive oxygen species produced by NADPH
      oxidase (Nox) are important risk factors of hypertension. The current study aims
      to examine the associations of Nox-related genes with longitudinal blood pressure
      (BP) changes and the risk of incident hypertension in the Genetic Epidemiology
      Network of Salt Sensitivity (GenSalt) follow-up study. A total of 1,768
      participants from 633 families were included in our analysis. Nine BP
      measurements were obtained in the morning at baseline and during two follow-up
      visits. The mixed-effect models were used to investigate the associations of 52
      tagged single-nucleotide polymorphisms in 11 Nox-related genes with BP changes
      and incident hypertension. Gene-based analyses were performed by truncated
      product method (TPM) and Versatile Gene-based Association Study (VEGAS). Over the
      7.2 years of follow-up, systolic BP (SBP) and diastolic BP (DBP) increased, and
      32.1% (512) of participants developed hypertension. SNPs rs12094228, rs16861188
      and rs12066019 in NCF2 were significantly associated with longitudinal change in
      SBP (Pinteraction = 1.1 * 10-3, 2.8 * 10-3 and 1.2 * 10-3, respectively). Gene
      based analyses revealed that NCF2 was significantly associated with SBP (PTPM =
      1.00 * 10-6, PVEGAS = 1.26 * 10-4) and DBP changes (PTPM = 5.84 * 10-4, PVEGAS =
      1.04 * 10-3). These findings suggested that NCF2 may play an important role in BP
      changes over time in the Han Chinese population.

PMID- 29463834
TI  - Family history of colorectal cancer in first-degree relatives and metachronous
      colorectal adenoma.
AB  - OBJECTIVES: Little is known about the relationship between having a first-degree
      relative (FDR) with colorectal cancer (CRC) and risk for metachronous colorectal
      adenoma (CRA) following polypectomy. METHODS: We pooled data from seven
      prospective studies of 7697 patients with previously resected CRAs to quantify
      the relationship between having a FDR with CRC and risk for metachronous adenoma.
      RESULTS: Compared with having no family history of CRC, a positive family history
      in any FDR was significantly associated with increased odds of developing any
      metachronous CRA (OR = 1.14; 95% CI = 1.01-1.29). Higher odds of CRA were
      observed among individuals with an affected mother (OR = 1.27; 95% CI = 1.05
      1.53) or sibling (OR = 1.34; 95% CI = 1.11-1.62) as compared with those without,
      whereas no association was shown for individuals with an affected father. Odds of
      having a metachronous CRA increased with number of affected FDRs, with ORs (95%
      CIs) of 1.07 (0.93-1.23) for one relative and 1.39 (1.02-1.91) for two or more.
      Younger age of diagnosis of a sibling was associated with higher odds of
      metachronous CRA, with ORs (95% CIs) of 1.66 (1.08-2.56) for diagnosis at <54
      years; 1.34 (0.89-2.03) for 55-64 years; and 1.10 (0.70-1.72) for >65 years (p
      trend = 0.008). Although limited by sample size, results for advanced
      metachronous CRA were similar to those for any metachronous CRA. CONCLUSIONS: A
      family history of CRC is related to a modestly increased odds of metachronous
      CRA. Future research should explore whether having a FDR with CRC, particularly
      at a young age, should have a role in risk stratification for surveillance
      colonoscopy.

PMID- 29463835
TI  - Strontium isotope ratios of human hair record intra-city variations in tap water
      source.
AB  - The oxygen (18O/16O) isotope analysis of hair is commonly applied to reconstruct
      an individual's residence history. However, region-of-origin as determined from
      oxygen isotope values (delta18O) alone is often spatially indistinct. Adding
      additional geochemical recorders can refine region-of-origin estimates. In this
      capacity, strontium (87Sr/86Sr) isotope analysis has attracted increased
      interest. While 87Sr/86Sr reflects the influences of local geology, 87Sr/86Sr of
      hair includes both external environmental signals as well as the internal dietary
      indicators. To better understand the impact of these contributions to the spatial
      signal encoded within 87Sr/86Sr of hair, human hair was collected from three
      locations within Salt Lake City, Utah along with the donor's sex. The 87Sr/86Sr
      and delta18O of hair and local tap water were measured. There were no significant
      relationships between sex and either delta18O or 87Sr/86Sr of hair, nor between
      collection location and the delta18O of hair. However, we found significant
      associations between collection location and 87Sr/86Sr of hair. These findings
      suggest that interactions with local water may be an important source of Sr to
      human hair and that the 87Sr/86Sr of hair may have the capacity to record
      differences in 87Sr/86Sr of tap waters on small spatial scales.

PMID- 29463836
TI  - Demographic analysis of arrhenotokous parthenogenesis and bisexual reproduction
      of Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae).
AB  - Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) is a serious pest
      that is capable of bisexual and arrhenotokous reproduction. In arrhenotokous
      reproduction, virgin females initially produce male offspring; later, when their
      sons are sexually mature, the mothers begin bisexual reproduction by carrying out
      oedipal mating with their sons. Because a virgin female produces many male
      offspring before oedipal mating occurs, multiple oedipal mating is common. In
      this study, we investigated the effect of multiple oedipal mating on the
      population growth of F. occidentalis by using the age-stage, two-sex life table
      theory. In the arrhenotokous cohorts, all unfertilized eggs developed into males.
      In the bisexual cohorts, the offspring sex ratio was significantly female biased
      with the mean number of female offspring and male offspring being 72.68 and
      29.00, respectively. These were the same as the net reproductive rate of female
      offspring and male offspring. In arrhenotokous cohorts, the number of males
      available for oedipal mating significantly affected the production of female
      offspring. The number of female offspring increased as the number of sons
      available for oedipal mating increased. Correctly characterizing this unique type
      of reproduction will provide important information for predicting the timing of
      future outbreaks of F. occidentalis, as well as aiding in formulating successful
      management strategies against the species.

PMID- 29463837
TI  - Giant circular dichroism of large-area extrinsic chiral metal nanocrecents.
AB  - In this work, we demonstrate the strong extrinsic chirality of the larger-area
      metal nanocrescents by experiments and simulations. Our results show that the
      metal nanocrescent exhibits giant and tunable circular dichroism (CD) effect,
      which is intensively dependent on the incident angle of light. We attribute the
      giant extrinsic chirality of the metal nanocrescent to the excitation
      efficiencies difference of localized surface plasmon resonance (LSPR) modes for
      two kinds of circularly polarized light at a non-zero incident angle. In
      experiment, the largest CD of 0.37 is obtained at the wavelength of 826 nm with
      the incident angle of 60 degrees . Furthermore, the CD spectra can be tuned
      flexibly by changing the metal nanocrescent diameter. Benefitting from the
      simple, low-cost and mature fabrication process, the proposed large-area metal
      nanocrescents are propitious to application.

PMID- 29463839
TI  - Heat transfer across a nanoscale pressurized air gap and its application in
      magnetic recording.
AB  - In this study, we investigated how a thermally actuated air bearing slider heats
      up a fast-spinning storage disk through a highly pressurized nanoscale air gap in
      a magnetic recording system. A Eulerian-description-based computational approach
      is developed considering heat conduction through a pressurized air film and near
      field radiation across the gap. A set of field equations that govern the air
      bearing dynamics, slider thermo-mechanics and disk heat dissipation are solved
      simultaneously through an iterative approach. A temperature field on the same
      order as the hot slider surface itself is found to be established in the disk.
      The effective local heat transfer coefficient is found to vary substantially with
      disk materials and linear speeds. This approach quantifies the magnitude of
      different thermal transport schemes and the accuracy is verified by an excellent
      agreement with our experiment, which measures the local slider temperature rise
      with a resistance temperature sensor. It also demonstrates an effective
      computational approach to treat transient thermal processes in a system of
      components with fast relative speed and different length scales. Finally, the
      investigated thermal transport mechanism leads to a substantial spacing change
      that has a significant impact on the spacing margin of today's magnetic storage
      systems.

PMID- 29463838
TI  - Interleukin-33 is activated by allergen- and necrosis-associated proteolytic
      activities to regulate its alarmin activity during epithelial damage.
AB  - Interleukin (IL)-33 is an IL-1 family alarmin released from damaged epithelial
      and endothelial barriers to elicit immune responses and allergic inflammation via
      its receptor ST2. Serine proteases released from neutrophils, mast cells and
      cytotoxic lymphocytes have been proposed to process the N-terminus of IL-33 to
      enhance its activity. Here we report that processing of full length IL-33 can
      occur in mice deficient in these immune cell protease activities. We sought
      alternative mechanisms for the proteolytic activation of IL-33 and discovered
      that exogenous allergen proteases and endogenous calpains, from damaged airway
      epithelial cells, can process full length IL-33 and increase its alarmin activity
      up to ~60-fold. Processed forms of IL-33 of apparent molecular weights ~18, 20,
      22 and 23 kDa, were detected in human lungs consistent with some, but not all,
      proposed processing sites. Furthermore, allergen proteases degraded processed
      forms of IL-33 after cysteine residue oxidation. We suggest that IL-33 can sense
      the proteolytic and oxidative microenvironment during tissue injury that
      facilitate its rapid activation and inactivation to regulate the duration of its
      alarmin function.

PMID- 29463840
TI  - Cranial shape comparison for automated objective 3D craniosynostosis surgery
      planning.
AB  - Virtual planning of open cranial vault reconstruction is used to simulate and
      define an pre-operative plan for craniosynostosis surgery. However, virtual
      planning techniques are subjective and dependent on the experience and
      preferences of the surgical team. To develop an objective automated 3D pre
      operative planning technique for open cranial vault reconstructions, we used
      curvature maps for the shape comparison of the patient's skull with an age
      specific reference skull. We created an average skull for the age-group of 11-14
      months. Also, we created an artificial test object and selected a cranial CT-scan
      of an 11 months old trigonocephaly patient as test case. Mesh data of skulls were
      created using marching cubes and raycasting. Curvature maps were computed using
      quadric surface fitting. The shape comparison was tested for the test object and
      the average skull. Finally, shape comparison was performed for the
      trigonocephalic skull with the average skull. Similar shapes and the area on the
      patient's skull that maximally corresponded in shape with the reference shape
      were correctly identified. This study showed that curvature maps allow the
      comparison of craniosynostosis skulls with age-appropriate average skulls and a
      first step towards an objective user-independent pre-operative planning technique
      for open cranial vault reconstructions is made.

PMID- 29463841
TI  - Chaotic Dynamics of Inner Ear Hair Cells.
AB  - Experimental records of active bundle motility are used to demonstrate the
      presence of a low-dimensional chaotic attractor in hair cell dynamics.
      Dimensionality tests from dynamic systems theory are applied to estimate the
      number of independent variables sufficient for modelling the hair cell response.
      Poincare maps are constructed to observe a quasiperiodic transition from chaos to
      order with increasing amplitudes of mechanical forcing. The onset of this
      transition is accompanied by a reduction of Kolmogorov entropy in the system and
      an increase in transfer entropy between the stimulus and the hair bundle,
      indicative of signal detection. A simple theoretical model is used to describe
      the observed chaotic dynamics. The model exhibits an enhancement of sensitivity
      to weak stimuli when the system is poised in the chaotic regime. We propose that
      chaos may play a role in the hair cell's ability to detect low-amplitude sounds.

PMID- 29463842
TI  - FOXQ1 controls the induced differentiation of melanocytic cells.
AB  - Oncogenic transcription factor FOXQ1 has been implicated in promotion of multiple
      transformed phenotypes in carcinoma cells. Recently, we have characterized FOXQ1
      as a melanoma tumor suppressor that acts via repression of N-cadherin gene, and
      invasion and metastasis. Here we report that FOXQ1 induces differentiation in
      normal and transformed melanocytic cells at least partially via direct
      transcriptional activation of MITF gene, melanocytic lineage-specific regulator
      of differentiation. Importantly, we demonstrate that pigmentation induced in
      cultured melanocytic cells and in mice by activation of cAMP/CREB1 pathway
      depends in large part on FOXQ1. Moreover, our data reveal that FOXQ1 acts as a
      critical mediator of BRAFV600E-dependent regulation of MITF levels, thus
      providing a novel link between two major signal transduction pathways controlling
      MITF and differentiation in melanocytic cells.

PMID- 29463843
TI  - Prostaglandin D2 amplifies lupus disease through basophil accumulation in
      lymphoid organs.
AB  - In systemic lupus erythematosus (SLE), autoantibody production can lead to kidney
      damage and failure, known as lupus nephritis. Basophils amplify the synthesis of
      autoantibodies by accumulating in secondary lymphoid organs. Here, we show a role
      for prostaglandin D2 (PGD2) in the pathophysiology of SLE. Patients with SLE have
      increased expression of PGD2 receptors (PTGDR) on blood basophils and increased
      concentration of PGD2 metabolites in plasma. Through an autocrine mechanism
      dependent on both PTGDRs, PGD2 induces the externalization of CXCR4 on basophils,
      both in humans and mice, driving accumulation in secondary lymphoid organs.
      Although PGD2 can accelerate basophil-dependent disease, antagonizing PTGDRs in
      mice reduces lupus-like disease in spontaneous and induced mouse models. Our
      study identifies the PGD2/PTGDR axis as a ready-to-use therapeutic modality in
      SLE.

PMID- 29463844
TI  - TRAF6 regulates EGF-induced cell transformation and cSCC malignant phenotype
      through CD147/EGFR.
AB  - TRAF6, a well-known adapter molecule, plays pivotal role in TLR/IL-1R associated
      signaling pathway. Although TRAF6 has been shown to have oncogenic activity in
      various malignant tumors, the details remain unclear. In this study, we
      demonstrated that TRAF6 facilitates Ras (G12V) and EGF-induced cellular
      transformation through EGFR. Silencing of TRAF6 expression significantly
      downregulated AP-1 activity, as well as MMP-2,9 expression after EGF stimulation.
      Furthermore, we found that TRAF6 plays an essential role in cutaneous squamous
      cell carcinoma (cSCC) malignant phenotypes, affecting cell growth and migration.
      CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin
      superfamily, is over-expressed in tumors and induces tumorigenesis. Our results
      showed that CD147 formed complex with EGFR and TRAF6. Knockdown of TRAF6
      disrupted the CD147-EGFR complex, thereby inducing EGFR endocytosis. Therefore,
      TRAF6 might be a novel molecular target for cSCC prevention or therapy.

PMID- 29463845
TI  - Identification of stable reference genes for quantitative PCR in koalas.
AB  - To better understand host and immune response to diseases, gene expression
      studies require identification of reference genes with stable expression for
      accurate normalisation. This study describes the identification and testing of
      reference genes with stable expression profiles in koala lymph node tissues
      across two genetically distinct koala populations. From the 25 most stable genes
      identified in transcriptome analysis, 11 genes were selected for verification
      using reverse transcription quantitative PCR, in addition to the commonly used
      ACTB and GAPDH genes. The expression data were analysed using stable genes
      statistical software - geNorm, BestKeeper, NormFinder, the comparative DeltaCt
      method and RefFinder. All 13 genes showed relative stability in expression in
      koala lymph node tissues, however Tmem97 and Hmg20a were identified as the most
      stable genes across the two koala populations.

PMID- 29463846
TI  - Alteration of rocks by endolithic organisms is one of the pathways for the
      beginning of soils on Earth.
AB  - Subaerial endolithic systems of the current extreme environments on Earth provide
      exclusive insight into emergence and development of soils in the Precambrian when
      due to various stresses on the surfaces of hard rocks the cryptic niches inside
      them were much more plausible habitats for organisms than epilithic ones. Using
      an actualistic approach we demonstrate that transformation of silicate rocks by
      endolithic organisms is one of the possible pathways for the beginning of soils
      on Earth. This process led to the formation of soil-like bodies on rocks in situ
      and contributed to the raise of complexity in subaerial geosystems. Endolithic
      systems of East Antarctica lack the noise from vascular plants and are among the
      best available natural models to explore organo-mineral interactions of a very
      old "phylogenetic age" (cyanobacteria-to-mineral, fungi-to-mineral, lichen-to
      mineral). On the basis of our case study from East Antarctica we demonstrate that
      relatively simple endolithic systems of microbial and/or cryptogamic origin that
      exist and replicate on Earth over geological time scales employ the principles of
      organic matter stabilization strikingly similar to those known for modern full
      scale soils of various climates.

PMID- 29463847
TI  - Small-Vessel Vasculopathy Due to Aberrant Autophagy in LAMP-2 Deficiency.
AB  - Lysosomal associated membrane protein 2 (LAMP2) is physiologically implicated in
      autophagy. A genetic LAMP2 defect causes Danon disease, which consists of two
      major phenotypes of myopathy and cardiomyopathy. In addition, arteriopathy may
      manifest on rare occasions but the pathological basis remains unknown. We
      encountered two Danon families that developed small-vessel vasculopathy in the
      coronary or cerebral arteries. To investigate the underlying mechanisms, we
      characterized the biological features of LAMP-2-deficient mice and cultured
      cells. LAMP-2-deficient mice at 9-24 months of age showed medial thickening with
      luminal stenosis due to proliferation of vascular smooth muscle cells (VSMC) in
      muscular arteries. Ultrastructural analysis of VSMC revealed various autophagic
      vacuoles scattered throughout the cytoplasm, suggesting impaired autophagy of
      long-lived metabolites and degraded organelles (i.e., mitochondria). The VSMC in
      Lamp2 null mice expressed more vimentin but less alpha-smooth muscle actin (alpha
      SMA), indicating a switch from contractile to synthetic phenotype. Silencing of
      LAMP2 in cultured human brain VSMC showed the same phenotypic transition with
      mitochondrial fragmentation, enhanced mitochondrial respiration, and
      overproduction of reactive oxygen species (ROS). These findings indicate that
      LAMP-2 deficiency leads to arterial medial hypertrophy with the phenotypic
      conversion of VSMC, resulting from age-dependent accumulation of cellular waste
      generated by aberrant autophagy.

PMID- 29463848
TI  - Autoantibodies against the Immunoglobulin-Binding Region of Ro52 Link its
      Autoantigenicity with Pathogen Neutralization.
AB  - Ro52/TRIM21 plays a key role in antibody-dependent pathogen neutralization and is
      a major autoantigen in systemic lupus erythematosus, Sjogren's syndrome (SS), and
      other autoimmune diseases. Here we evaluated immunoreactivity against Ro52
      related molecules in SS and healthy volunteers. Although most proteins examined
      were not antigenic, several TRIM paralogs, including TRIM22, and TRIM38, showed
      sporadic immunoreactivity in SS. In contrast, the murine Ro52 ortholog with
      limited linear homology demonstrated high levels of autoantibodies implicating
      the importance of shared conformational epitopes. To further explore the
      autoantigencity of Ro52, deletion and point mutant analyses were employed
      revealing previously hidden, robust autoantibodies directed against its C
      terminal immunoglobulin-binding domain. Another autoantibody, rheumatoid factor,
      targeting the Fc region of IgG, strongly overlapped with Ro52 seropositivity
      (odds ratio 14; P < 0.0001). These convergent mechanistic findings support a
      model whereby intracellular Ro52-bound antibody-coated pathogen complexes,
      released or misprocessed from infected cells, drive autoantigenicity against Ro52
      and the Fc region of IgG.

PMID- 29463849
TI  - Reconstruction of kidney renal clear cell carcinoma evolution across pathological
      stages.
AB  - Although numerous studies on kidney renal clear cell carcinoma (KIRC) were
      carried out, the dynamic process of tumor formation was not clear yet. Inadequate
      attention was paid on the evolutionary paths among somatic mutations and their
      clinical implications. As the tumor initiation and evolution of KIRC were
      primarily associated with SNVs, we reconstructed an evolutionary process of KIRC
      using cross-sectional SNVs in different pathological stages. KIRC driver genes
      appeared early in the evolutionary tree, and the genes with moderate mutation
      frequency showed a pattern of stage-by-stage expansion. Although the individual
      gene mutations were not necessarily associated with survival outcome, the
      evolutionary paths such as VHL-PBRM1 and FMN2-PCLO could indicate stage-specific
      prognosis. Our results suggested that, besides mutation frequency, the
      evolutionary relationship among the mutated genes could facilitate to identify
      novel drivers and biomarkers for clinical utility.

PMID- 29463850
TI  - Microglia-mediated recovery from ALS-relevant motor neuron degeneration in a
      mouse model of TDP-43 proteinopathy.
AB  - Though motor neurons selectively degenerate in amyotrophic lateral sclerosis,
      other cell types are likely involved in this disease. We recently generated rNLS8
      mice in which human TDP-43 (hTDP-43) pathology could be reversibly induced in
      neurons and expected that microglia would contribute to neurodegeneration.
      However, only subtle microglial changes were detected during disease in the
      spinal cord, despite progressive motor neuron loss; microglia still reacted to
      inflammatory triggers in these mice. Notably, after hTDP-43 expression was
      suppressed, microglia dramatically proliferated and changed their morphology and
      gene expression profiles. These abundant, reactive microglia selectively cleared
      neuronal hTDP-43. Finally, when microgliosis was blocked during the early
      recovery phase using PLX3397, a CSF1R and c-kit inhibitor, rNLS8 mice failed to
      regain full motor function, revealing an important neuroprotective role for
      microglia. Therefore, reactive microglia exert neuroprotective functions in this
      amyotrophic lateral sclerosis model, and definition of the underlying mechanism
      could point toward novel therapeutic strategies.

PMID- 29463851
TI  - DNA-based identification reveals illegal trade of threatened shark species in a
      global elasmobranch conservation hotspot.
AB  - Here, we report trading of endangered shark species in a world hotspot for
      elasmobranch conservation in Brazil. Data on shark fisheries are scarce in
      Brazil, although the northern and northeastern regions have the highest indices
      of shark bycatch. Harvest is made primarily with processed carcasses lacking head
      and fins, which hampers reliable species identification and law enforcement on
      illegal catches. We used partial sequences of two mitochondrial genes (COI and/or
      NADH2) to identify 17 shark species from 427 samples being harvested and marketed
      on the northern coast of Brazil. Nine species (53%) are listed under some
      extinction threat category according to Brazilian law and international
      authorities (IUCN - International Union for Conservation of Nature; CITES -
      Convention on International Trade of Endangered Species of Wild Fauna and Flora).
      The number increases to 13 (76%) if we also consider the Near Threatened
      category. Hammerhead sharks are under threat worldwide, and composed 18.7% of
      samples, with Sphyrna mokarran being the fourth most common species among
      samples. As illegal trade of threatened shark species is a worldwide conservation
      problem, molecular identification of processed meat or specimens lacking
      diagnostic body parts is a highly effective tool for species identification and
      law enforcement.

PMID- 29463852
TI  - Iodine insertion and dispersion of refractive index in organic single crystal
      semiconductor.
AB  - Insertion of halogens such as bromine or iodine affects the electronic
      polarizability of ions and the local field inside the medium, and thus modifies
      the refractive index. Acquiring precise knowledge of the dispersion of refractive
      index and ultimately tailoring conventional semiconductors for wide-range
      refractive index control have been a vital issue to resolve before realizing
      advanced organic optoelectronic devices. In this report, dispersions of the
      refractive index of a single crystal tetramethyltetraselenafulvalene [C10H12Se4]
      (TMTSF) are thoroughly studied from broadband interference modulations of
      photoluminescence (PL) spectra at various temperatures and doping levels. A large
      enhancement of the refractive index, more than 20% of the intrinsic value, is
      achieved with inclusion of a small composition of iodide ions, while the
      structural and optical properties remain mostly intact. Nearly temperature
      independent dispersion of the refractive index suggests that, unlike most
      polymers in which the thermal expansion coefficient dominates over the change of
      polarizability with temperature, the latter enhances significantly and may become
      more or less comparable to the thermal expansion coefficient given by 1.71 * 10
      4/K, when single crystal TMTSF is doped by iodine.

PMID- 29463853
TI  - Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes
      and Zic2 reduce bone mass in young mice.
AB  - Fractures are a common comorbidity in children with the neural tube defect (NTD)
      spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute
      to NTDs in humans and mice, but whether this pathway independently determines
      bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP
      components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we
      performed detailed uCT comparisons of bone structure in tibiae from young male
      mice heterozygous for NTD-associated mutations versus WT littermates. PCP
      signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+)
      mutations significantly reduced trabecular bone mass and distal tibial cortical
      thickness. NTD-associated mutations in non-PCP transcription factors were also
      investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2
      mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula
      junction and diminished cortical bone in the proximal tibia. Beyond these genes,
      we bioinformatically documented the known extent of shared genetic networks
      between NTDs and bone properties. 46 genes involved in neural tube closure are
      annotated with bone-related ontologies. These findings document shared genetic
      networks between spina bifida risk and bone structure, including PCP components
      and Zic2. Genetic variants which predispose to spina bifida may therefore
      independently diminish bone mass.

PMID- 29463854
TI  - Autologous stem cell transplantation for primary mediastinal B-cell lymphoma:
      long-term outcome and role of post-transplant radiotherapy. A report of the
      European Society for Blood and Marrow Transplantation.
AB  - The purpose of this retrospective registry study was to investigate the outcome
      of autoSCT for primary mediastinal B-cell lymphoma (PMBCL) in the rituximab era,
      including the effects of eventual post-transplant radiotherapy (RT)
      consolidation. Patients with PMBCL aged between 18 and 70 years who were treated
      with a first autoSCT between 2000 and 2012 and registered with the EBMT were
      eligible. Eighty-six patients with confirmed PMBCL and the full data set required
      for this analysis were evaluable. Sixteen patients underwent autoSCT in remission
      after first-line therapy (CR/PR1), 44 patients were transplanted with
      chemosensitive relapsed or primary refractory disease (CR/PR >1), and 24 patients
      were chemorefractory at the time of autoSCT. With a median follow-up of 5 years,
      3-year estimates of relapse incidence, progression-free survival, and overall
      survival were 6%, 94%, and 100% for CR/PR1; 31%, 64%, and 85% for CR/PR >1; and
      52%, 39%, and 41% for REF, respectively. Whilst there was no significant benefit
      of post-transplant RT in the CR/PR >1 group, RT could completely prevent disease
      recurrence post d100 in the refractory group. In conclusion, autoSCT with or
      without consolidating RT is associated with excellent outcome in
      chemoimmunotherapy-sensitive PMBCL, whereas its benefits seem to be limited in
      chemoimmunotherapy-refractory disease.

PMID- 29463855
TI  - Zearalenone altered the cytoskeletal structure via ER stress- autophagy-
      oxidative stress pathway in mouse TM4 Sertoli cells.
AB  - The aim of this study was to investigate the molecular mechanisms of the
      destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4
      cells. In order to investigate the role of autophagy, oxidative stress and
      endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal
      structure, the effects of ZEA on the cell viability, cytoskeletal structure,
      autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling
      pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal
      structure through the induction of autophagy that leads to the alteration of
      cytoskeletal structure via elevated oxidative stress. Our results further showed
      that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling
      pathways in TM4 cells. In addition, ZEA also induced the ER stress which was
      involved in the induction of the autophagy through inhibiting the ERK signal
      pathway to suppress the phosphorylation of mTOR. ER stress was involved in the
      damage of cytoskeletal structure through induction of autophagy by producing ROS.
      Taken together, this study revealed that ZEA altered the cytoskeletal structure
      via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.

PMID- 29463856
TI  - Impact of Reduced Cerebellar EAAT Expression on Purkinje Cell Firing Pattern of
      NPC1-deficient Mice.
AB  - Niemann-Pick disease Type C1 (NPC1) is a rare hereditary neurodegenerative
      disease. NPC1-patients suffer, amongst others, from ataxia, based on a loss of
      cerebellar Purkinje cells (PCs). Impaired expression/function of excitatory amino
      acid transporters (EAATs) are suspected of contributing to PC-degeneration in
      hereditary spinocerebellar ataxias (SCAs). Thus, we studied EAAT-expression and
      its impact to PC-activity in NPC1-/-mice. Western blot revealed reduced EAAT1,
      EAAT2, EAAT4, and betaIII-spectrin levels in NPC1-/-mice. EAATs play a crucial
      role in synaptic transmission, thus we were interested in the impact of the
      reduced EAAT-expression on the function of PCs. Patch-clamp recordings of PCs
      showed no differences in the firing patterns of NPC1+/+and NPC1-/-mice using a
      low internal chloride concentration. Because EAAT4 also comprises a chloride
      permeable ion pore, we perturbed the chloride homeostasis using a high internal
      chloride concentration. We observed differences in the firing patterns of
      NPC1+/+and NPC1-/-mice, suggesting an impact of the altered EAAT4-expression.
      Additionally, the EAAT-antagonist DL-TBOA acts differently in NPC1+/+and NPC1-/
      mice. Our data support the line of evidence that an altered EAAT
      expression/function is involved in neurodegeneration of PCs observed in SCAs.
      Thus, we suggest that similar pathogenic mechanisms contribute the loss of PCs in
      NPC1.

PMID- 29463857
TI  - Consequences of asynchronous heading in a perennial bunchgrass (Elymus excelsus).
AB  - Reproduction is vital to plant population adaptation. The consequences of
      asynchronous reproduction in a perennial bunchgrass grass is not well studied.
      The heading reproductive tillers from early to late forms a continuum due to
      asynchronous heading and flowering in Elymus excelsus population. In two peak
      years of production, the three-year-old and four-year-old reproductive tillers of
      experimental E. excelsus population were marked from the early to late heading
      stage every four days at five different heading times and these tillers were
      harvested at the dough stage, respectively. The growth, biomass, seed production
      and reproductive allocation were measured to analyze the consequences of
      asynchronous reproduction. Reproductive tiller height, biomass, inflorescence
      length, inflorescence biomass, floret number, seed number, seed biomass, seed-set
      percentage, biomass allocation to inflorescence (RA1) and to seed (RA2)
      significantly decreased with the delay of heading date over the two years. Above
      ten phenotypic characteristics exponentially increased at a significant or
      extremely significant level with increasing differences in reproductive period.
      Reproductive tillers preferentially allocated the biomass to inflorescences, and
      then the inflorescences preferentially allocated the biomass to seeds throughout
      reproductive period. Earlier heading tillers had more contribution to E. excelsus
      population adaptation and development in the two peak years of production.

PMID- 29463858
TI  - Clinical and genetic spectrum of AMPD2-related pontocerebellar hypoplasia type 9.
AB  - Pontocerebellar hypoplasia (PCH) represents a group of autosomal-recessive
      progressive neurodegenerative disorders of prenatal onset. Eleven PCH subtypes
      are classified according to clinical, neuroimaging and genetic findings.
      Individuals with PCH type 9 (PCH9) have a unique combination of postnatal
      microcephaly, hypoplastic cerebellum and pons, and hypoplastic or absent corpus
      callosum. PCH9 is caused by biallelic variants in AMPD2 encoding adenosine
      monophosphate deaminase 2; however, a homozygous AMPD2 frameshift variant has
      recently been reported in two family members with spastic paraplegia type 63
      (SPG63). We identified homozygous or compound heterozygous AMPD2 variants in
      eight PCH-affected individuals from six families. The eight variants likely
      affect function and comprise one frameshift, one nonsense and six missense
      variants; seven of which were novel. The main clinical manifestations in the
      eight new patients and 17 previously reported individuals with biallelic AMPD2
      variants were postnatal microcephaly, severe global developmental delay,
      spasticity, and central visual impairment. Brain imaging data identified
      hypomyelination, hypoplasia of the cerebellum and pons, atrophy of the cerebral
      cortex, complete or partial agenesis of the corpus callosum and the "figure 8"
      shape of the hypoplastic midbrain as consistent features. We broaden the AMPD2
      related clinical spectrum by describing one individual without microcephaly and
      absence of the characteristic "figure 8" shape of the midbrain. The existence of
      various AMPD2 isoforms with different functions possibly explains the variability
      in phenotypes associated with AMPD2 variants: variants leaving some of the
      isoforms intact may cause SPG63, while those affecting all isoforms may result in
      the severe and early-onset PCH9.

PMID- 29463859
TI  - Biomining of MoS2 with Peptide-based Smart Biomaterials.
AB  - Biomining of valuable metals using a target specific approach promises increased
      purification yields and decreased cost. Target specificity can be implemented
      with proteins/peptides, the biological molecules, responsible from various
      structural and functional pathways in living organisms by virtue of their
      specific recognition abilities towards both organic and inorganic materials.
      Phage display libraries are used to identify peptide biomolecules capable of
      specifically recognizing and binding organic/inorganic materials of interest with
      high affinities. Using combinatorial approaches, these molecular recognition
      elements can be converted into smart hybrid biomaterials and harnessed for
      biotechnological applications. Herein, we used a commercially available phage
      display library to identify peptides with specific binding affinity to
      molybdenite (MoS2) and used them to decorate magnetic NPs. These peptide-coupled
      NPs could capture MoS2 under a variety of environmental conditions. The same
      batch of NPs could be re-used multiple times to harvest MoS2, clearly suggesting
      that this hybrid material was robust and recyclable. The advantages of this smart
      hybrid biomaterial with respect to its MoS2-binding specificity, robust
      performance under environmentally challenging conditions and its recyclability
      suggests its potential application in harvesting MoS2 from tailing ponds and
      downstream mining processes.

PMID- 29463860
TI  - The path to metastatic mouse models of colorectal cancer.
AB  - The study and comprehension of the molecular mechanisms underlying cancer biology
      strongly rely on mouse modeling. An ideal mouse model should have molecular,
      histopathological, and etiological characteristics as close as possible to those
      of the corresponding human tumors. Among solid tumors, colorectal cancer (CRC) is
      one of the malignancies that best suits reproduction in an animal model: it
      evolves through a progressive set of molecular events and is generally associated
      with a precise histopathology and a neat cataloging of stages and grades. The
      development of refined CRC mouse models over several decades has seen them
      recently evolve toward sophisticated systems that ever more closely approximate
      the human pathology, with different models addressing different human CRC
      subtypes. In particular, a metastatic CRC model has been seen as a "holy grail"
      in this field, and we describe in this review the path taken to achieve
      metastatic models and discuss the path forward.

PMID- 29463862
TI  - Intraoperative head drift and eye movement: two under addressed challenges during
      cataract surgery.
AB  - PURPOSE: To objectively measure head drift during cataract surgery, and
      subjectively simulate eye movements and assess impact on surgical technique.
      MATERIALS AND METHODS: Twelve consecutively recorded routine cataract operations
      in the Tennent Institute of Ophthalmology, Gartnavel General Hospital, Glasgow,
      were reviewed. The speculum was used as a fixed point and correlated with a
      superimposed virtual ruler to measure maximum head drift in each direction
      throughout the operations. To simulate intraoperative eye movement, we attached
      string to the cataract surgical simulator (Eyesi) eye and manually induced
      abduction and adduction. A calibrated scale secured to the Eyesi head ensured 5
      mm eye movements were consistently created. Ophthalmology trainees performed the
      continuous curvilinear capsulorhexis (CCC) exercise without and with sequential
      eye movements. Movements were induced every three seconds. Scores were compared
      using a paired Student's T-test. RESULTS: Mean head drift in the surgical
      recordings was 3.1 mm medially (range 2-7 mm), 2.9 mm laterally (range 2-4 mm),
      2.6 mm superiorly (range 1-5 mm), and 1.9 mm inferiorly (range 1-4 mm). In 11 of
      12 cases, the operating microscope had to be adjusted for head drift. Six junior
      trainees completed the CCC module on the Eyesi without then with eye movements.
      After introducing eye movements the mean Eyesi score reduced from 92.7 to 76.9 (P
      = 0.014), 'roundness of rhexis' score reduced from 89.4 to 57.5 (P = 0.020), and
      trainees operated 17 s faster (P = 0.016). CONCLUSION: This study objectively
      demonstrates the under-reported clinical scenario of head drift during cataract
      surgery. By manipulating the Eyesi we have shown that eye movements reduce the
      quality of cataract surgery.

PMID- 29463861
TI  - Beyond molecular tumor heterogeneity: protein synthesis takes control.
AB  - One of the daunting challenges facing modern medicine lies in the understanding
      and treatment of tumor heterogeneity. Most tumors show intra-tumor heterogeneity
      at both genomic and proteomic levels, with marked impacts on the responses of
      therapeutic targets. Therapeutic target-related gene expression pathways are
      affected by hypoxia and cellular stress. However, the finding that targets such
      as eukaryotic initiation factor (eIF) 4E (and its phosphorylated form, p-eIF4E)
      are generally homogenously expressed throughout tumors, regardless of the
      presence of hypoxia or other cellular stress conditions, opens the exciting
      possibility that malignancies could be treated with therapies that combine
      targeting of eIF4E phosphorylation with immune checkpoint inhibitors or
      chemotherapy.

PMID- 29463863
TI  - Proposal for a new classification for ocular surface squamous neoplasia.

PMID- 29463864
TI  - Lateral tarsal strip versus Bick's procedure in correction of eyelid malposition.
AB  - OBJECTIVES: To compare the functional and anatomical outcomes of lateral tarsal
      strip (LTS) with Bick's procedure in treatment of eyelid malposition. METHODS: A
      retrospective, consecutive case series of patients who underwent LTS and Bick's
      procedure for all types of involutional lower eyelid malposition, at two centers
      between January 2012 and 2015. Statistical analyses of differences between groups
      were performed using the Fisher's exact test to compare non-continuous variables
      and Mann-Whitney U test for continuous variables. RESULTS: A total of 641
      procedures (557 LTS and 84 Bick's) were performed on 504 patients (137 bilateral)
      by 7 consultants and their trainees. The study cohort included 286 males and 218
      females. The mean age was 76.2 years (median 78). The mean follow-up was 13.07
      months (median 7, range 0.5-58 months). The indications for surgery included
      ectropion (43.2%), entropion (39.9%), eyelid laxity (12.3%), floppy eyelid
      syndrome (2.7%), and others (1.9%). At last follow-up, the LTS group achieved
      89.1% anatomical success (total + partial correction) compared to 100% in Bick's
      group (P < 0.001). Functional improvement was 82% and 95% in LTS and Bick's
      groups, respectively (P = 0.002). Consultants and trainee doctors achieved
      comparable outcomes within each group. Complications were relatively minor with
      no major long-term sequelae, nor any statistically significant difference between
      the two groups in terms of frequency of adverse events (16.9% vs 14.2%, P =
      0.929). The reoperation rate was 9% in the LTS group during the study period,
      compared to none in the Bick's group (P = 0.001). CONCLUSIONS: This study
      compares the outcomes of the largest reported cohort of eyelid malposition
      surgery analyzing the two different techniques for lid margin shortening. Bick's
      procedure achieved statistically significant better anatomical and functional
      outcomes compared to LTS although the samples were unequal and not randomized.

PMID- 29463865
TI  - Enhanced Biological Response of AVS-Functionalized Ti-6Al-4V Alloy through
      Covalent Immobilization of Collagen.
AB  - This study presents the development of an efficient procedure for covalently
      immobilizing collagen molecules on AVS-functionalized Ti-6Al-4V samples, and the
      assessment of the survival and proliferation of cells cultured on these
      substrates. Activated Vapor Silanization (AVS) is a versatile functionalization
      technique that allows obtaining a high density of active amine groups on the
      surface. A procedure is presented to covalently bind collagen to the functional
      layer using EDC/NHS as cross-linker. The covalently bound collagen proteins are
      characterized by fluorescence microscopy and atomic force microscopy and their
      stability is tested. The effect of the cross-linker concentration on the process
      is assessed. The concentration of the cross-linker is optimized and a reliable
      cleaning protocol is developed for the removal of the excess of carbodiimide from
      the samples. The results demonstrate that the covalent immobilization of collagen
      type I on Ti-6Al-4V substrates, using the optimized protocol, increases the
      number of viable cells present on the material. Consequently, AVS in combination
      with the carbodiimide chemistry appears as a robust method for the immobilization
      of proteins and, for the first time, it is shown that it can be used to enhance
      the biological response to the material.

PMID- 29463866
TI  - Hybridized Tungsten Oxide Nanostructures for Food Quality Assessment: Fabrication
      and Performance Evaluation.
AB  - Tungsten oxide based micro and nanosized structures possess good capacitance as
      well as enhanced rate capability. Such properties are useful in various
      applications including electrochemical supercapacitors. Apart from
      supercapacitance, WO3 and their 2D integrated structures have been modified using
      different methods to widen their range of the utility. Modification using layer
      coating, functionalization with other nanomaterial or molecules are methods that
      can be used to improve the core structure of WO3. But such modifications often
      alter electrochemical performance. The effects and outcomes of such modifications
      incorporated in WO3 structures were studied using electrochemical methods,
      sensing behavior, and morphological examination. One goal for such modifications
      was to improve robustness of the WO3 structures apart from any change in
      supercapacitance performance. After detailed electrochemical analyses of WO3
      structures, a preliminary study was performed regarding the feasibility of the
      WO3 based sensors for food safety applications based on electrochemical detection
      of hazardous dyes in food. Preliminary results obtained after various
      electrochemical tests including pulsed voltammetry, cyclic voltammetry, and
      electrochemical impedance spectroscopy suggest the viability of WO3 structures
      for food safety applications.

PMID- 29463867
TI  - Optogenetic Tractography for anatomo-functional characterization of cortico
      subcortical neural circuits in non-human primates.
AB  - Dissecting neural circuitry in non-human primates (NHP) is crucial to identify
      potential neuromodulation anatomical targets for the treatment of
      pharmacoresistant neuropsychiatric diseases by electrical neuromodulation. How
      targets of deep brain stimulation (DBS) and cortical targets of transcranial
      magnetic stimulation (TMS) compare and might complement one another is an
      important question. Combining optogenetics and tractography may enable anatomo
      functional characterization of large brain cortico-subcortical neural pathways.
      For the proof-of-concept this approach was used in the NHP brain to characterize
      the motor cortico-subthalamic pathway (m_CSP) which might be involved in DBS
      action mechanism in Parkinson's disease (PD). Rabies-G-pseudotyped and Rabies-G
      VSVg-pseudotyped EIAV lentiviral vectors encoding the opsin ChR2 gene were
      stereotaxically injected into the subthalamic nucleus (STN) and were retrogradely
      transported to the layer of the motor cortex projecting to STN. A precise
      anatomical mapping of this pathway was then performed using histology-guided high
      angular resolution MRI tractography guiding accurately cortical photostimulation
      of m_CSP origins. Photoexcitation of m_CSP axon terminals or m_CSP cortical
      origins modified the spikes distribution for photosensitive STN neurons firing
      rate in non-equivalent ways. Optogenetic tractography might help design
      preclinical neuromodulation studies in NHP models of neuropsychiatric disease
      choosing the most appropriate target for the tested hypothesis.

PMID- 29463868
TI  - CD38 promotes pristane-induced chronic inflammation and increases susceptibility
      to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism.
AB  - In this study, we investigated the role of CD38 in a pristane-induced murine
      model of lupus. CD38-deficient (Cd38-/-) but not ART2-deficient (Art2-/-) mice
      developed less severe lupus compared to wild type (WT) mice, and their protective
      phenotype consisted of (i) decreased IFN-I-stimulated gene expression, (ii)
      decreased numbers of peritoneal CCR2hiLy6Chi inflammatory monocytes, TNF-alpha
      producing Ly6G+ neutrophils and Ly6Clo monocytes/macrophages, (iii) decreased
      production of anti-single-stranded DNA and anti-nRNP autoantibodies, and (iv)
      ameliorated glomerulonephritis. Cd38-/- pristane-elicited peritoneal exudate
      cells had defective CCL2 and TNF-alpha secretion following TLR7 stimulation.
      However, Tnf-alpha and Cxcl12 gene expression in Cd38-/- bone marrow (BM) cells
      was intact, suggesting a CD38-independent TLR7/TNF-alpha/CXCL12 axis in the BM.
      Chemotactic responses of Cd38-/- Ly6Chi monocytes and Ly6G+ neutrophils were not
      impaired. However, Cd38-/- Ly6Chi monocytes and Ly6Clo monocytes/macrophages had
      defective apoptosis-mediated cell death. Importantly, mice lacking the cation
      channel TRPM2 (Trpm2-/-) exhibited very similar protection, with decreased
      numbers of PECs, and apoptotic Ly6Chi monocytes and Ly6Clo monocytes/macrophages
      compared to WT mice. These findings reveal a new role for CD38 in promoting
      aberrant inflammation and lupus-like autoimmunity via an apoptosis-driven
      mechanism. Furthermore, given the implications of CD38 in the activation of
      TRPM2, our data suggest that CD38 modulation of pristane-induced apoptosis is
      TRPM2-dependent.

PMID- 29463869
TI  - Angiotensin-converting enzyme inhibitor reduces scar formation by inhibiting both
      canonical and noncanonical TGF-beta1 pathways.
AB  - Angiotensin-converting enzyme inhibitors (ACEIs) can improve the fibrotic
      processes in many internal organs. Recent studies have shown a relationship
      between ACEI with cutaneous scar formation, although it has not been confirmed,
      and the underlying mechanism is unclear. In this study, we cultured mouse NIH 3T3
      fibroblasts with different concentrations of ACEI. We measured cell proliferation
      with a Cell Counting Kit-8 and collagen expression with a Sirius Red Collagen
      Detection Kit. Flow cytometry and western blotting were used to detect
      transforming growth factor beta1 (TGF-beta1) signaling. We also confirmed the
      potential antifibrotic activity of ACEI in a rat scar model. ACEI reduced
      fibroblast proliferation, suppressed collagen and TGF-beta1 expression, and
      downregulated the phosphorylation of SMAD2/3 and TAK1, both in vitro and in vivo.
      A microscopic examination showed that rat scars treated with ramipril or losartan
      were not only narrower than in the controls, but also displayed enhanced re
      epithelialization and neovascularization, and the formation of organized
      granulation tissue. These data indicate that ACEI inhibits scar formation by
      suppressing both TGF-beta1/SMAD2/3 and TGF-beta1/TAK1 pathways, and may have
      clinical utility in the future.

PMID- 29463870
TI  - A novel P300 BCI speller based on the Triple RSVP paradigm.
AB  - A brain-computer interface (BCI) is an advanced human-machine interaction
      technology. The BCI speller is a typical application that detects the stimulated
      source-induced EEG signal to identify the expected characters of the subjects.
      The current mainstream matrix-based BCI speller involves two problems that remain
      unsolved, namely, gaze-dependent and space-dependent problems. Some scholars have
      designed gaze-independent and space-independent spelling systems. However, this
      system still cannot achieve a satisfactory information transfer rate (ITR). In
      this paper, we propose a novel triple RSVP speller with gaze-independent and
      space-independent characteristics and higher ITR. The triple RSVP speller uses
      rapid serial visual presentation (RSVP) paradigm, each time presents three
      different characters, and each character is presented three times to increase the
      ITR. The results of the experiments show the triple RSVP speller online average
      accuracy of 0.790 and average online ITR of 20.259 bit/min, where the system
      spelled at a speed of 10 s per character, and the stimulus presentation interface
      is a 90 * 195 pixel rectangle. Thus, the triple RSVP speller can be integrated
      into mobile smart devices (such as smartphones, smart watches, and others).

PMID- 29463871
TI  - Co-treatment with clonidine and a GRK2 inhibitor prevented rebound hypertension
      and endothelial dysfunction after withdrawal in diabetes.
AB  - Hypertension and diabetes are associated with a risk of cardiovascular disease.
      Clonidine is currently used as a fourth-line drug therapy for hypertension
      because of its rebound hypertensive effect and short half-life. The purpose of
      this study was to investigate the combined effect of an antihypertensive drug
      (clonidine) and a G-protein-coupled receptor kinase 2 (GRK2) inhibitor on rebound
      hypertension and endothelial dysfunction. The clonidine and/or GRK2 inhibitor
      were administered by continuous infusion for 14 days by using an osmotic pump
      that was implanted subcutaneously. To test the effects of GRK2 inhibitotr, we
      measured blood pressure by using a tail-cuff system in diabetic mice in which
      rebound hypertension was induced by withdrawal after clonidine treatment and
      measured vascular responses in isolated aortas from these mice. The mice were
      then euthanized 7 days later. We observed that, in diabetes mellitus (DM) mice,
      blood pressure began to decline after 3 days of clonidine or clonidine + GRK2
      inhibitor infusion. However, 15 days after initiation of treatment, the blood
      pressure of the clonidine only-treated DM mice began to increase and resulted in
      a high final blood pressure. At 21 days, clonidine withdrawal triggered rebound
      hypertension together with impaired endothelium-dependent relaxation, increased
      GRK2 activity, and reduced Akt/endothelial NO synthase (eNOS)/NO production in
      aortas. Conversely, withdrawal of the combination clonidine/GRK2-inhibitor
      treatment did not cause rebound hypertension, and normal induction of endothelium
      dependent relaxation, decreased GRK2 activity, and increased Akt/eNOS were
      observed in aortas from DM mice. These results suggest that suppression of GRK2
      activity affects rebound hypertension-associated vascular endothelial dysfunction
      by targeting the Akt/eNOS signaling pathway.

PMID- 29463872
TI  - Near-100 MeV protons via a laser-driven transparency-enhanced hybrid acceleration
      scheme.
AB  - The range of potential applications of compact laser-plasma ion sources motivates
      the development of new acceleration schemes to increase achievable ion energies
      and conversion efficiencies. Whilst the evolving nature of laser-plasma
      interactions can limit the effectiveness of individual acceleration mechanisms,
      it can also enable the development of hybrid schemes, allowing additional degrees
      of control on the properties of the resulting ion beam. Here we report on an
      experimental demonstration of efficient proton acceleration to energies exceeding
      94 MeV via a hybrid scheme of radiation pressure-sheath acceleration in an
      ultrathin foil irradiated by a linearly polarised laser pulse. This occurs via a
      double-peaked electrostatic field structure, which, at an optimum foil thickness,
      is significantly enhanced by relativistic transparency and an associated jet of
      super-thermal electrons. The range of parameters over which this hybrid scenario
      occurs is discussed and implications for ion acceleration driven by next
      generation, multi-petawatt laser facilities are explored.

PMID- 29463873
TI  - Induction of micronuclei by four cytostatic compounds in human hematopoietic stem
      cells and human lymphoblastoid TK6 cells.
AB  - For mutagenicity testing, primary lymphocytes or mammalian cell lines are
      employed. However, the true target for carcinogenic action of mutagenic chemicals
      may be stem cells. Since hematopoietic cancers induced by chemical agents
      originate at the hematopoietic stem cell (HSC) stage and since one of the side
      effects of chemotherapeutic cancer treatment is the induction of secondary
      tumors, often leukemias, HSC may be a suitable cell system. We compared the
      sensitivity of HSC with the genotoxicity testing cell line TK6 for chromosomal
      mutations. HSC were less sensitive than TK6 cells for the genotoxic effects of
      the model genotoxins and chemotherapeutic agents doxorubicin, vinblastine, methyl
      methanesulfonate (MMS) and equally sensitive for mitomycin C (MMC). However, loss
      of viability after mitomycin C treatment was higher in HSC than in TK6 cells.
      Among the factors that may influence sensitivity for genomic damage, the
      generation or response to reactive oxygen species (ROS) and the effectiveness of
      DNA damage response can be discussed. Here we show that HSC can be used in a
      standard micronucleus test protocol for chromosomal mutations and that their
      sensitivity was not higher than that of a classical testing cell line.

PMID- 29463874
TI  - Prominent exostosis projecting from the occipital squama more substantial and
      prevalent in young adult than older age groups.
AB  - Recently we reported the development of prominent exostosis young adults' skulls
      (41%; 10-31 mm) emanating from the external occipital protuberance (EOP). These
      findings contrast existing reports that large enthesophytes are not seen in young
      adults. Here we show that a combination sex, the degree of forward head
      protraction (FHP) and age predicted the presence of enlarged EOP (EEOP) (n =
      1200, age 18-86). While being a male and increased FHP had a positive effect on
      prominent exostosis, paradoxically, increase in age was linked to a decrease in
      enthesophyte size. Our latter findings provide a conundrum, as the frequency and
      severity of degenerative skeletal features in humans are associated typically
      with aging. Our findings and the literature provide evidence that mechanical load
      plays a vital role in the development and maintenance of the enthesis (insertion)
      and draws a direct link between aberrant loading of the enthesis and related
      pathologies. We hypothesize EEOP may be linked to sustained aberrant postures
      associated with the emergence and extensive use of hand-held contemporary
      technologies, such as smartphones and tablets. Our findings raise a concern about
      the future musculoskeletal health of the young adult population and reinforce the
      need for prevention intervention through posture improvement education.

PMID- 29463875
TI  - Proliferation and apoptosis of T lymphocytes in patients with bipolar disorder.
AB  - The aim of the study was to evaluate proliferation capacity and susceptibility to
      apoptosis of T lymphocytes of patients with bipolar disorder (BD) and to
      investigate in vitro influence of two standard mood stabilizers: lithium and
      valproic acid on these parameters using flow cytometry. Our results show that T
      lymphocytes of BD patients, especially those treated with lithium, have reduced
      proliferation capacity compared to healthy people. In vitro studies showed that
      valproic acid reduces the number of cell divisions and percentages of
      proliferating cells regardless of health status but mainly in very high dose,
      while lithium has no significant influence on proliferation capacity of patients'
      T lymphocytes. Lymphocytes of BD patients are also more prone to apoptosis
      compared with healthy individuals which is related to high expression of Bax, a
      pro-apoptotic protein. In vitro lithium protected patients' lymphocytes from
      apoptosis proportionally to dose used. Valproic acid protected lymphocytes of
      patients from apoptosis mainly in therapeutic concentration. Our results show
      that mood stabilizers used to prevent relapses of the disease have anti-apoptotic
      effect on T lymphocytes of BD patients but they are not able to improve their
      proliferation capacity.

PMID- 29463876
TI  - Publisher Correction: Associations of statin use with motor performance and
      myalgia may be modified by 25-hydroxyvitamin D: findings from a British birth
      cohort.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 29463877
TI  - Cinnamaldehyde accelerates wound healing by promoting angiogenesis via up
      regulation of PI3K and MAPK signaling pathways.
AB  - The bark of Cinnamomum cassia (C. cassia) has been used for the management of
      coronary heart disease (CHD) and diabetes mellitus. C. cassia may target the
      vasculature, as it stimulates angiogenesis, promotes blood circulation and wound
      healing. However, the active components and working mechanisms of C. cassia are
      not fully elucidated. The Shexiang Baoxin pill (SBP), which consists of seven
      medicinal materials, including C. cassia etc., is widely used as a traditional
      Chinese patent medicine for the treatment of CHD. Here, 22 single effective
      components of SBP were evaluated against the human umbilical vein endothelial
      cells (HUVECs). We demonstrated that in HUVECs, cinnamaldehyde (CA) stimulated
      proliferation, migration, and tube formation. CA also activated the
      phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK)
      pathways. Furthermore, the secretion of vascular endothelial growth factor (VEGF)
      from HUVECs was increased by CA. In vivo, CA partially restored intersegmental
      vessels in zebrafish pretreated with PTK787, which is a selective inhibitor for
      vascular endothelial growth factor receptor (VEGFR). CA also showed pro
      angiogenic efficacy in the Matrigel plug assay. Additionally, CA attenuated wound
      sizes in a cutaneous wound model, and elevated VEGF protein and CD31-positive
      vascular density at the margin of these wounds. These results illustrate that CA
      accelerates wound healing by inducing angiogenesis in the wound area. The
      potential mechanism involves activation of the PI3K/AKT and MAPK signaling
      pathways. Such a small non-peptide molecule may have clinical applications for
      promoting therapeutic angiogenesis in chronic diabetic wounds and myocardial
      infarction.

PMID- 29463878
TI  - Glutathione peroxidase 4 overexpression inhibits ROS-induced cell death in
      diffuse large B-cell lymphoma.
AB  - Regulation of oxidative stress and redox systems has important roles in
      carcinogenesis and cancer progression, and for this reason has attracted much
      attention as a new area of cancer therapeutic targets. Glutathione peroxidase 4
      (GPX4), an antioxidant enzyme, has biological important functions such as
      signaling cell death by suppressing peroxidation of membrane phospholipids.
      However, few studies exist on the expression and clinical relevance of GPX4 in
      malignant lymphomas such as diffuse large B-cell lymphoma. In this study, we
      assessed the expression of GPX4 immunohistochemically. GPX4 was expressed in
      35.5% (33/93) cases of diffuse large B-cell lymphoma. The GPX4-positive group had
      poor overall survival (P = 0.0032) and progression-free survival (P = 0.0004)
      compared with those of the GPX4-negative group. In a combined analysis of GPX4
      and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, there was a
      negative correlation between GPX4 and 8-hydroxydeoxyguanosine (P = 0.0009). The
      GPX4-positive and 8-hydroxydeoxyguanosine-negative groups had a significantly
      worse prognosis than the other groups in both overall survival (P = 0.0170) and
      progression-free survival (P = 0.0005). These results suggest that the
      overexpression of GPX4 is an independent prognostic predictor in diffuse large B
      cell lymphoma. Furthermore, in vitro analysis demonstrated that GPX4
      overexpressing cells were resistant to reactive oxygen species-induced cell death
      (P = 0.0360). Conversely, GPX4-knockdown cells were sensitive to reactive oxygen
      species-induced cell death (P = 0.0111). From these data, we conclude that GPX4
      regulates reactive oxygen species-induced cell death. Our results suggest a novel
      therapeutic strategy using the mechanism of ferroptosis, as well as a novel
      prognostic predictor of diffuse large B-cell lymphoma.

PMID- 29463880
TI  - Salvaging the supernatant: next generation cytopathology for solid tumor mutation
      profiling.
AB  - With the expanding role of targeted therapy in patients with solid tumors,
      pathologists face the daunting task of having to maximize limited volume tissue
      obtained by fine needle aspiration for a variety of molecular tests. While most
      molecular studies on fine needle aspiration samples have been reported using
      cellular material, recent studies have shown that a substantial amount of DNA can
      be retrieved from the supernatant fluid of aspirate needle rinses after cell
      pelleting for cytospin or cell block preparations. In routine clinical workflow,
      the supernatant is discarded; however this fluid may provide a complementary
      source of DNA for tumor mutational profiling. In this study, we evaluated the
      post-centrifuged supernatant from 25 malignant and 10 benign fine needle
      aspiration needle rinses. The mean and median DNA yields from the supernatants
      were 445 ng and 176.4 ng (range, 15.1-2958 ng), respectively. Next generation
      sequencing using the Ion AmpliSeq Cancer Hotspot Panel v2 detected somatic
      mutations in all 25 malignant samples. No mutations were detected in any of the
      benign samples tested. When available, mutations detected in the supernatant
      fluid were compared to the next generation sequencing analysis performed on a
      prior or concurrent surgical specimen from the same patient and showed 100%
      concordance. In a subset of cases (n = 19) mutations in EGFR, KRAS, BRAF, PIK3CA,
      and NRAS were successfully confirmed by droplet digital PCR, providing an
      orthogonal platform for mutation analysis. In summary, in this study we show that
      post centrifuged supernatants from fine needle aspiration needle rinses can
      provide a robust substrate for expanded mutation profiling by next generation
      sequencing, as well as hotspot mutation testing by droplet digital PCR. The
      ability to detect somatic mutations from otherwise discarded supernatant fluids
      offers the ability to triage and effectively utilize limited volume fine needle
      aspiration samples when multiple molecular tests are requested, without the need
      to re-biopsy for additional tissue samples.

PMID- 29463879
TI  - Redox control of vascular smooth muscle cell function and plasticity.
AB  - Vascular smooth muscle cells (SMC) play a major role in vascular diseases, such
      as atherosclerosis and hypertension. It has long been established in vitro that
      contractile SMC can phenotypically switch to function as proliferative and/or
      migratory cells in response to stimulation by oxidative stress, growth factors,
      and inflammatory cytokines. Reactive oxygen species (ROS) are oxidative stressors
      implicated in driving vascular diseases, shifting cell bioenergetics, and
      increasing SMC proliferation, migration, and apoptosis. In this review, we
      summarize our current knowledge of how disruptions to redox balance can
      functionally change SMC and how this may influence vascular disease pathogenesis.
      Specifically, we focus on our current understanding of the role of vascular
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) 1, 4, and 5 in
      SMC function. We also review the evidence implicating mitochondrial fission in
      SMC phenotypic transitions and mitochondrial fusion in maintenance of SMC
      homeostasis. Finally, we discuss the importance of the redox regulation of the
      soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP)-protein
      kinase G (PKG) pathway as a potential oxidative and therapeutic target for
      regulating SMC function.

PMID- 29463881
TI  - Stroma modifies relationships between risk factor exposure and age-related
      epithelial involution in benign breast.
AB  - Delayed age-related lobular involution has been previously associated with
      elevated breast cancer risk. However, intraindividual variability in epithelial
      involution status within a woman is undefined. We developed a novel measure of
      age-related epithelial involution, density of epithelial nuclei in epithelial
      areas using digital image analysis in combination with stromal characteristics
      (percentage of section area comprising stroma). Approximately 1800 hematoxylin
      and eosin stained sections of benign breast tissue were evaluated from 416
      participants having breast surgery for cancer or benign conditions. Two to
      sixteen slides per woman from different regions of the breast were studied.
      Epithelial involution status varied within a woman and as a function of stromal
      area. Percentage stromal area varied between samples from the same woman (median
      difference between highest and lowest stromal area within a woman was 7.5%, but
      ranged from 0.01 to 86.7%). Restricting to women with at least 10% stromal area
      (N = 317), epithelial nuclear density decreased with age (-637.1 cells/mm2 per
      decade of life after age 40, p < 0.0001), increased with mammographic density
      (457.8 cells/mm2 per increasing BI-RADs density category p = 0.002), and
      increased non-significantly with recent parity, later age at first pregnancy, and
      longer and more recent oral contraceptive use. These associations were attenuated
      in women with mostly fat samples (<10% stroma (N = 99)). Thirty-one percent of
      women evaluated had both adequate stroma (>=10%) and mostly fat (<10% stroma)
      regions of breast tissue, with the probability of having both types increasing
      with the number breast tissue samplings. Several breast cancer risk factors are
      associated with elevated age-related epithelial content, but associations depend
      upon stromal context. Stromal characteristics appear to modify relationships
      between risk factor exposures and breast epithelial involution.

PMID- 29463883
TI  - Frequent and differential mutations of the CYLD gene in basal cell salivary
      neoplasms: linkage to tumor development and progression.
AB  - Basal cell salivary neoplasms display similar cyto-morphologic features and are
      classified into adenoma and adenocarcinoma based on the presence or absence of
      tumor invasion at diagnosis. These neoplasms also share considerable phenotypic
      resemblance and co-exist with certain dermal adnexal tumors harboring the CYLD
      gene mutations inferring common genetic association. We sequenced the CYLD gene
      in both basal cell adenomas and adenocarcinomas and correlated the findings with
      CYLD, NF-kappaB, and beta-catenin expression levels and clinicopathologic
      factors. Twenty mutations were identified and comprised of 3 synonymous and 17
      non-synonymous (missense) types involving the coding exons of the CYLD gene.
      Mutations in exons 9-11 were identified in both adenomas and adenocarcinomas,
      while mutations in exons 12-20, encoding the USP domain, were exclusively found
      in carcinomas. Although no significant correlation between CYLD mutations and
      expression levels of CYLD, NF-kappaB, and beta-catenin or clinicopathologic
      parameters was found, basal cell adenocarcinomas with multiple mutations showed
      reduction in CYLD protein expression and pursued aggressive clinical behavior.
      Our study revealed high incidence and sequential CYLD mutations in both basal
      cell adenoma and adenocarcinoma supporting a single neoplastic continuum for
      their evolution and provides evidence for potential diagnostic and therapeutic
      utility.

PMID- 29463882
TI  - The genetics of recurrent hydatidiform moles: new insights and lessons from a
      comprehensive analysis of 113 patients.
AB  - Hydatidiform mole is an aberrant human pregnancy characterized by early embryonic
      arrest and excessive trophoblastic proliferation. Recurrent hydatidiform moles
      are defined by the occurrence of at least two hydatidiform moles in the same
      patient. Fifty to eighty percent of patients with recurrent hydatidiform moles
      have biallelic pathogenic variants in NLRP7 or KHDC3L. However, in the remaining
      patients, the genotypic types of the moles are unknown. We characterized 80 new
      hydatidiform mole tissues, 57 of which were from patients with no mutations in
      the known genes, and we reviewed the genotypes of a total of 123 molar tissues.
      We also reviewed mutation analysis in 113 patients with recurrent hydatidiform
      moles. While all hydatidiform moles from patients with biallelic NLRP7 or KHDC3L
      mutations are diploid biparental, we demonstrate that those from patients without
      mutations are highly heterogeneous and only a small minority of them are diploid
      biparental (8%). The other mechanisms that were found to recur in patients
      without mutations are diploid androgenetic monospermic (24%) and triploid
      dispermic (32%); the remaining hydatidiform moles were misdiagnosed as moles due
      to errors in the analyses and/or their unusual mechanisms. We compared three
      parameters of genetic susceptibility in patients with and without mutations and
      show that patients without mutations are mostly from non-familial cases, have
      fewer reproductive losses, and more live births. Our data demonstrate that
      patients with recurrent hydatidiform moles and no mutations in the known genes
      are, in general, different from those with mutations; they have a milder genetic
      susceptibility and/or a multifactorial etiology underlying their recurrent
      hydatidiform moles. Categorizing these patients according to the genotypic types
      of their recurrent hydatidiform moles may facilitate the identification of novel
      genes for this entity.

PMID- 29463884
TI  - Tumor-infiltrating lymphocytes and ductal carcinoma in situ of the breast:
      friends or foes?
AB  - In the past three decades, the detection rate of ductal carcinoma in situ of the
      breast has dramatically increased due to breast screening programs. As a
      consequence, about 20% of all breast cancer cases are detected in this early in
      situ stage. Some ductal carcinoma in situ cases will progress to invasive breast
      cancer, while other cases are likely to have an indolent biological behavior. The
      presence of tumor-infiltrating lymphocytes is seen as a promising prognostic and
      predictive marker in invasive breast cancer, mainly in HER2-positive and triple
      negative subtypes. Here, we summarize the current understanding regarding immune
      infiltrates in invasive breast cancer and highlight recent observations regarding
      the presence and potential clinical significance of such immune infiltrates in
      patients with ductal carcinoma in situ. The presence of tumor-infiltrating
      lymphocytes, their numbers, composition, and potential relationship with genomic
      status will be discussed. Finally, we propose that a combination of genetic and
      immune markers may better stratify ductal carcinoma in situ subtypes with respect
      to tumor evolution.

PMID- 29463885
TI  - Machine learning for the meta-analyses of microbial pathogens' volatile
      signatures.
AB  - Non-invasive and fast diagnostic tools based on volatolomics hold great promise
      in the control of infectious diseases. However, the tools to identify microbial
      volatile organic compounds (VOCs) discriminating between human pathogens are
      still missing. Artificial intelligence is increasingly recognised as an essential
      tool in health sciences. Machine learning algorithms based in support vector
      machines and features selection tools were here applied to find sets of microbial
      VOCs with pathogen-discrimination power. Studies reporting VOCs emitted by human
      microbial pathogens published between 1977 and 2016 were used as source data. A
      set of 18 VOCs is sufficient to predict the identity of 11 microbial pathogens
      with high accuracy (77%), and precision (62-100%). There is one set of VOCs
      associated with each of the 11 pathogens which can predict the presence of that
      pathogen in a sample with high accuracy and precision (86-90%). The implemented
      pathogen classification methodology supports future database updates to include
      new pathogen-VOC data, which will enrich the classifiers. The sets of VOCs
      identified potentiate the improvement of the selectivity of non-invasive
      infection diagnostics using artificial olfaction devices.

PMID- 29463886
TI  - A set of regulatory genes co-expressed in embryonic human brain is implicated in
      disrupted speech development.
AB  - Genetic investigations of people with impaired development of spoken language
      provide windows into key aspects of human biology. Over 15 years after FOXP2 was
      identified, most speech and language impairments remain unexplained at the
      molecular level. We sequenced whole genomes of nineteen unrelated individuals
      diagnosed with childhood apraxia of speech, a rare disorder enriched for
      causative mutations of large effect. Where DNA was available from unaffected
      parents, we discovered de novo mutations, implicating genes, including CHD3,
      SETD1A and WDR5. In other probands, we identified novel loss-of-function variants
      affecting KAT6A, SETBP1, ZFHX4, TNRC6B and MKL2, regulatory genes with links to
      neurodevelopment. Several of the new candidates interact with each other or with
      known speech-related genes. Moreover, they show significant clustering within a
      single co-expression module of genes highly expressed during early human brain
      development. This study highlights gene regulatory pathways in the developing
      brain that may contribute to acquisition of proficient speech.

PMID- 29463887
TI  - Dipyrimicin A and B, microbial compounds isolated from Amycolatopsis sp. K16
      0194.
AB  - In a search for compounds interacting with ergosterol resin, a new compound named
      dipyrimicin B was isolated from a rare actinomycete strain, Amycolatopsis sp. K16
      0194. In addition, another analog, dipyrimicin A, which does not interact with
      the resin, was also discovered. The structures of the two dipyrimicins were
      established by comprehensive 1D and 2D NMR and MS analyses and found to contain a
      unique core structure, a 2,2'-bipyridine skeleton. Dipyrimicin A showed strong
      antimicrobial and cytotoxic activity, whereas dipyrimicin B displayed distinctly
      poor antimicrobial and cytotoxic activities.

PMID- 29463888
TI  - Furanoaustinol and 7-acetoxydehydroaustinol: new meroterpenoids from a marine
      derived fungal strain Penicillium sp. SF-5497.
AB  - Two new meroterpenoid-type fungal metabolites, furanoaustinol (1) and 7
      acetoxydehydroaustinol (2), were isolated from the ethyl acetate extract of a
      marine-derived fungal strain Penicillium sp. SF-5497, along with eight (3-10)
      known meroterpenoids. Their structures were elucidated mainly based on the
      analysis of their NMR (1D and 2D) and MS data. Particularly, the novel
      meroterpenoid, furanoaustinol (1), belonging to the austin group, was identified
      to possess an unprecedented hexacyclic ring system. Biological evaluation of
      these compounds revealed that furanoaustinol (1) weakly inhibited the activity of
      protein tyrosine phosphatase 1B in a dose-dependent manner with an IC50 value of
      77.2 MUM. In addition, 7-acetoxydehydroaustinol (2) and four other known
      meroterpenoids (5, 7, 9, and 10) weakly suppressed the overproduction of nitric
      oxide in lipopolysaccharide-challenged BV2 microglial cells with IC50 values of
      61.0, 30.1, 58.3, 37.6, and 40.2 MUM, respectively.

PMID- 29463889
TI  - Rational design of syn-safencin, a novel linear antimicrobial peptide derived
      from the circular bacteriocin safencin AS-48.
AB  - Bacteriocins hold unprecedented promise as a largely untapped source of
      antibiotic alternatives in the age of multidrug resistance. Here, we describe the
      first approach to systematically design variants of a novel AS-48 bacteriocin
      homologue, which we have termed safencin AS-48, from Bacillus safensis, to gain
      insights into engineering improved activity of bacteriocins. A library of
      synthetic peptides in which systematic amino acid substitutions to vary the
      periodicity and abundance of polar, acidic, aliphatic, and hydrophobic residues
      were generated for a total of 96 novel peptide variants of a single bacteriocin
      candidate. Using this method, we identified nine synthetic safencin (syn
      safencin) variants with broad and potent antimicrobial activities with minimal
      inhibitory concentrations (MIC) as low as 250 nM against E. coli, P. aeruginosa,
      X. axonopodis, and S. pyogenes with minimal cytotoxicity to mammalian cells. It
      is anticipated that the strategies we have developed will serve as general guides
      for tuning the specificity of a given natural bacteriocin compound for
      therapeutic specificity.

PMID- 29463890
TI  - Iron and phosphorus deprivation induce sociality in the marine bloom-forming
      cyanobacterium Trichodesmium.
AB  - Trichodesmium spp. are diazotrophic cyanobacteria that exist as single filaments
      (trichomes) and as macroscopic colonies of varying shapes formed by aggregating
      trichomes. The causes and dynamics of colony formation and disassociation are not
      yet elucidated. we demonstrate that limited availability of dissolved phosphorus
      (P) or iron (Fe) stimulated trichome mobility and induced colony formation in
      Trichodesmium erythraeum IMS101 cultures. The specific nutrient limitation
      differentially affected the rate of colony formation and morphology of the
      colonies. Fe starvation promoted rapid colony formation (10-48 h from depletion)
      while 5-7 days were required for colonies to form in P-depleted cultures. Video
      analyses confirmed that the probability of trichomes to cluster increased from 12
      to 35% when transferred from nutrient replete to Fe-depleted conditions.
      Moreover, the probability for Fe-depleted aggregates to remain colonial increased
      to 50% from only 10% in nutrient replete cultures. These colonies were also
      characterized by stronger attachment forces between the trichomes. Enrichment of
      nutrient-depleted cultures with the limited nutrient-stimulated colony
      dissociation into single trichomes. We postulate that limited P and Fe
      availability enhance colony formation of Trichodesmium and primarily control the
      abundance and distribution of its different morphologies in the nutrient-limited
      surface ocean.

PMID- 29463891
TI  - Specialized plant biochemistry drives gene clustering in fungi.
AB  - The fitness and evolution of prokaryotes and eukaryotes are affected by the
      organization of their genomes. In particular, the physical clustering of genes
      can coordinate gene expression and can prevent the breakup of co-adapted alleles.
      Although clustering may thus result from selection for phenotype optimization and
      persistence, the impact of environmental selection pressures on eukaryotic genome
      organization has rarely been systematically explored. Here, we investigated the
      organization of fungal genes involved in the degradation of phenylpropanoids, a
      class of plant-produced secondary metabolites that mediate many ecological
      interactions between plants and fungi. Using a novel gene cluster detection
      method, we identified 1110 gene clusters and many conserved combinations of
      clusters in a diverse set of fungi. We demonstrate that congruence in genome
      organization over small spatial scales is often associated with similarities in
      ecological lifestyle. Additionally, we find that while clusters are often
      structured as independent modules with little overlap in content, certain gene
      families merge multiple modules into a common network, suggesting they are
      important components of phenylpropanoid degradation strategies. Together, our
      results suggest that phenylpropanoids have repeatedly selected for gene
      clustering in fungi, and highlight the interplay between genome organization and
      ecological evolution in this ancient eukaryotic lineage.

PMID- 29463892
TI  - Microbial cycling of isoprene, the most abundantly produced biological volatile
      organic compound on Earth.
AB  - Isoprene (2-methyl-1,3-butadiene), the most abundantly produced biogenic volatile
      organic compound (BVOC) on Earth, is highly reactive and can have diverse and
      often detrimental atmospheric effects, which impact on climate and health. Most
      isoprene is produced by terrestrial plants, but (micro)algal production is
      important in aquatic environments, and the relative bacterial contribution
      remains unknown. Soils are a sink for isoprene, and bacteria that can use
      isoprene as a carbon and energy source have been cultivated and also identified
      using cultivation-independent methods from soils, leaves and coastal/marine
      environments. Bacteria belonging to the Actinobacteria are most frequently
      isolated and identified, and Proteobacteria have also been shown to degrade
      isoprene. In the freshwater-sediment isolate, Rhodococcus strain AD45, initial
      oxidation of isoprene to 1,2-epoxy-isoprene is catalyzed by a multicomponent
      isoprene monooxygenase encoded by the genes isoABCDEF. The resultant epoxide is
      converted to a glutathione conjugate by a glutathione S-transferase encoded by
      isoI, and further degraded by enzymes encoded by isoGHJ. Genome sequence analysis
      of actinobacterial isolates belonging to the genera Rhodococcus, Mycobacterium
      and Gordonia has revealed that isoABCDEF and isoGHIJ are linked in an operon,
      either on a plasmid or the chromosome. In Rhodococcus strain AD45 both isoprene
      and epoxy-isoprene induce a high level of transcription of 22 contiguous genes,
      including isoABCDEF and isoGHIJ. Sequence analysis of the isoA gene, encoding the
      large subunit of the oxygenase component of isoprene monooxygenase, from isolates
      has facilitated the development of PCR primers that are proving valuable in
      investigating the ecology of uncultivated isoprene-degrading bacteria.

PMID- 29463893
TI  - Consistent changes in the taxonomic structure and functional attributes of
      bacterial communities during primary succession.
AB  - Ecologists have long studied primary succession, the changes that occur in
      biological communities after initial colonization of an environment. Most of this
      work has focused on succession in plant communities, laying the conceptual
      foundation for much of what we currently know about community assembly patterns
      over time. Because of their prevalence and importance in ecosystems, an
      increasing number of studies have focused on microbial community dynamics during
      succession. Here, we conducted a meta-analysis of bacterial primary succession
      patterns across a range of distinct habitats, including the infant gut, plant
      surfaces, soil chronosequences, and aquatic environments, to determine whether
      consistent changes in bacterial diversity, community composition, and functional
      traits are evident over the course of succession. Although these distinct
      habitats harbor unique bacterial communities, we were able to identify patterns
      in community assembly that were shared across habitat types. We found an increase
      in taxonomic and functional diversity with time while the taxonomic composition
      and functional profiles of communities became less variable (lower beta
      diversity) in late successional stages. In addition, we found consistent
      decreases in the rRNA operon copy number and in the high-efficient phosphate
      assimilation process (Pst system) suggesting that reductions in resource
      availability during succession select for taxa adapted to low-resource
      conditions. Together, these results highlight that, like many plant communities,
      microbial communities also exhibit predictable patterns during primary
      succession.

PMID- 29463894
TI  - Coral bleaching from a single cell perspective.
AB  - Ocean warming is resulting in increased occurrence of mass coral bleaching; a
      response in which the intracellular algal endosymbionts (Symbiodinium sp.) are
      expelled from the coral host due to physiological stress. This detrimental
      process is often attributed to overproduction of reactive oxygen species (ROS)
      that leak out of the endosymbionts and causes damage to the host cell, though
      direct evidence validating this link is limited. Here, for the first time, we
      used confocal microscopy and fluorescent dyes to investigate if endosymbiont ROS
      production significantly and predictably affects physiological parameters in its
      host cell. Heat treatment resulted in a 60% reduction in coral symbiont density,
      a ~70% increase in median endosymbiont ROS and a small reduction in photosystem
      efficiency (FV/FM, 11%), indicating absence of severe light stress. Notably, no
      other physiological parameters were affected in either endosymbionts or host
      cells, including reduced glutathione and ROS-induced lipid peroxidation. Taken
      together, the increase in endosymbiont ROS could not be linked to physiological
      damage in either partner, suggesting that oxidative stress is unlikely to have
      been the driver for symbiont expulsion in this study.

PMID- 29463895
TI  - Cryptophyta as major bacterivores in freshwater summer plankton.
AB  - Small bacterivorous eukaryotes play a cardinal role in aquatic food webs and
      their taxonomic classification is currently a hot topic in aquatic microbial
      ecology. Despite increasing interest in their diversity, core questions regarding
      predator-prey specificity remain largely unanswered, e.g., which heterotrophic
      nanoflagellates (HNFs) are the main bacterivores in freshwaters and which
      prokaryotes support the growth of small HNFs. To answer these questions, we fed
      natural communities of HNFs from Rimov reservoir (Czech Republic) with five
      different bacterial strains of the ubiquitous betaproteobacterial genera
      Polynucleobacter and Limnohabitans. We combined amplicon sequencing and catalyzed
      reporter deposition fluorescence in situ hybridization (CARD-FISH) targeting
      eukaryotic 18 S rRNA genes to track specific responses of the natural HNF
      community to prey amendments. While amplicon sequencing provided valuable
      qualitative data and a basis for designing specific probes, the number of reads
      was insufficient to accurately quantify certain eukaryotic groups. We also
      applied a double-hybridization technique that allows simultaneous phylogenetic
      identification of both predator and prey. Our results show that community
      composition of HNFs is strongly dependent upon prey type. Surprisingly,
      Cryptophyta were the most abundant bacterivores, although this phylum has been so
      far assumed to be mainly autotrophic. Moreover, the growth of a small lineage of
      Cryptophyta (CRY1 clade) was strongly stimulated by one Limnohabitans strain in
      our experiment. Thus, our study is the first report that colorless Cryptophyta
      are major bacterivores in summer plankton samples and can play a key role in the
      carbon transfer from prokaryotes to higher trophic levels.

PMID- 29463896
TI  - Flexible migratory choices of Cory's shearwaters are not driven by shifts in
      prevailing air currents.
AB  - Wind conditions strongly affect migratory costs and shape flyways and detours for
      many birds, especially soaring birds. However, whether winds also influence
      individual variability in migratory choices is an unexplored question. Cory's
      shearwaters (Calonectris borealis) exhibit migratory flexibility, changing non
      breeding destination across the Atlantic Ocean within and between years. Here, we
      investigated how wind dynamics affect the spatiotemporal migratory behaviour and
      whether they influence individual choices of non-breeding destination. We
      analysed 168 GLS tracks of migratory Cory's shearwaters over five years in
      relation to concurrent wind data. We found no evidence for an association of the
      use of specific paths or destinations with particular wind conditions. Our
      results suggest that shearwaters deliberately choose their non-breeding
      destination, even when the choice entails longer distances and higher energetic
      costs for displacement due to unfavourable wind conditions en route. Favourable
      winds trigger migration only when directed towards specific areas but not to
      others. Despite their dependence on wind for dynamic soaring, Cory's shearwaters
      show a high individuality in migratory behaviour that cannot be explained by
      individual birds encountering different meteorological conditions at departure or
      during migratory movements.

PMID- 29463897
TI  - Molecular basis for histidine N1 position-specific methylation by CARNMT1.

PMID- 29463898
TI  - Uncoupling therapeutic from immunotherapy-related adverse effects for safer and
      effective anti-CTLA-4 antibodies in CTLA4 humanized mice.
AB  - Anti-CTLA-4 monoclonal antibodies (mAbs) confer a cancer immunotherapeutic effect
      (CITE) but cause severe immunotherapy-related adverse events (irAE). Targeting
      CTLA-4 has shown remarkable long-term benefit and thus remains a valuable tool
      for cancer immunotherapy if the irAE can be brought under control. An animal
      model, which recapitulates clinical irAE and CITE, would be valuable for
      developing safer CTLA-4-targeting reagents. Here, we report such a model using
      mice harboring the humanized Ctla4 gene. In this model, the clinically used drug,
      Ipilimumab, induced severe irAE especially when combined with an anti-PD-1
      antibody; whereas another mAb, L3D10, induced comparable CITE with very mild irAE
      under the same conditions. The irAE corresponded to systemic T cell activation
      and resulted in reduced ratios of regulatory to effector T cells (Treg/Teff)
      among autoreactive T cells. Using mice that were either homozygous or
      heterozygous for the human allele, we found that the irAE required bi-allelic
      engagement, while CITE only required monoallelic engagement. As with the
      immunological distinction for monoallelic vs bi-allelic engagement, we found that
      bi-allelic engagement of the Ctla4 gene was necessary for preventing conversion
      of autoreactive T cells into Treg cells. Humanization of L3D10, which led to loss
      of blocking activity, further increased safety without affecting the therapeutic
      effect. Taken together, our data demonstrate that complete CTLA-4 occupation,
      systemic T cell activation and preferential expansion of self-reactive T cells
      are dispensable for tumor rejection but correlate with irAE, while blocking B7
      CTLA-4 interaction impacts neither safety nor efficacy of anti-CTLA-4 antibodies.
      These data provide important insights for the clinical development of safer and
      potentially more effective CTLA-4-targeting immunotherapy.

PMID- 29463899
TI  - Silencing of developmental genes by H3K27me3 and DNA methylation reflects the
      discrepant plasticity of embryonic and extraembryonic lineages.

PMID- 29463900
TI  - Modifications and functional genomics of human transfer RNA.
AB  - Transfer RNA (tRNA) is present at tens of millions of transcripts in a human cell
      and is the most abundant RNA in moles among all cellular RNAs. tRNA is also the
      most extensively modified RNA with, on an average, 13 modifications per molecule.
      The primary function of tRNA as the adaptor of amino acids and the genetic code
      in protein synthesis is well known. tRNA modifications play multi-faceted roles
      in decoding and other cellular processes. The abundance, modification, and
      aminoacylation (charging) levels of tRNAs contribute to mRNA decoding in ways
      that reflect the cell type and its environment; however, how these factors work
      together to maximize translation efficiency remains to be understood. tRNAs also
      interact with many proteins not involved in translation and this may coordinate
      translation activity and other processes in the cell. This review focuses on the
      modifications and the functional genomics of human tRNA and discusses future
      perspectives on the explorations of human tRNA biology.

PMID- 29463902
TI  - Upregulation of SOX2-activated lncRNA ANRIL promotes nasopharyngeal carcinoma
      cell growth.
AB  - Recent molecularly targeted approaches have gained advances in nasopharyngeal
      carcinoma treatment. However, the estimated five-year survival rate has not met
      the desired degree of improvement. Here, we report that upregulation of the
      expression of the SOX2-activated lncRNA ANRIL is involved in nasopharyngeal
      carcinoma. ANRIL has been found to be upregulated in clinical nasopharyngeal
      carcinoma. Using genetic approaches targeting ANRIL in nasopharyngeal carcinoma
      cells, we found that the knockdown of ANRIL inhibits cell proliferation in vitro
      and in vivo. Mechanistically, SOX2 binds with ANRIL and increases its RNA level,
      which upregulates beta-catenin signalling, resulting in enhanced nasopharyngeal
      carcinoma tumourigenesis. Expression levels of ANRIL are positively correlated
      with SOX2 and beta-catenin in clinical nasopharyngeal carcinoma samples. Our
      findings demonstrate that the SOX2-ANRIL-beta-catenin axis plays a critical role
      in nasopharyngeal carcinoma proliferation and provide a potential therapeutic
      approach for nasopharyngeal carcinoma patients.

PMID- 29463901
TI  - Poly(ADP-ribose) mediates asymmetric division of mouse oocyte.
AB  - Before fertilization, mammalian oocyte undergoes an asymmetric division which
      depends on eccentric positioning of the spindle at the oocyte cortex to form a
      polar body and an egg. Since the centriole is absent and, as a result, the polar
      array microtubules are not fully developed in oocytes, microtubules have seldom
      been considered as required for eccentric positioning of the spindle, while actin
      related forces have instead been proposed to be primarily responsible for this
      process. However, the existing models are largely conflicting and the underlying
      mechanism of asymmetric division is still elusive. Here we show that poly(ADP
      ribose) (PAR) is enriched at mouse oocyte cortical area throughout meiosis.
      Specific removal of cortical PAR results in an ectopic spindle and a failure of
      asymmetric division. During spindle migration, when the spindle deviates from the
      center of oocyte by a pushing force of cytoplasmic actin, the short polar array
      microtubules emanating from the juxtacortical spindle pole extend to the cortex
      and penetrate into cortical PAR, docking and stabilizing the spindle at the
      cortex which facilitates the asymmetric division. This process depends on the
      affinity between PAR and microtubule-associated proteins such as Spindly, which
      contributes to a physical link for cortical PAR and the spindle. Notably, fusing
      a PAR-binding domain to end-binding protein 3, a plus-end tracking protein at the
      polar array microtubules, restores the asymmetric division of oocytes with
      Spindly knockdown. Thus, our work demonstrates a comprehensive mechanism for
      oocyte spindle positioning and asymmetric division.

PMID- 29463903
TI  - Feasibility of using urinary N7-(2-carbamoyl-2-hydroxyethyl) Guanine as a
      biomarker for acrylamide exposed workers.
AB  - Acrylamide (AA), a probable human carcinogen, is a widely-used industrial
      chemical but is also present in tobacco smoke and carbohydrate-rich foods
      processed at high temperatures. AA is metabolized to glycidamide (GA) to cause
      the formation of DNA adducts. N7-(2-carbamoyl-2-hydroxyethyl) guanine (N7-GAG),
      the most abundant DNA adduct induced by GA, was recently detected in urine of
      smokers and non-smokers. In this study, we assessed the variability of AA
      exposure and biomarkers of AA exposure in urine samples repeatedly collected from
      AA-exposed workers and explored the half-life of N7-GAG. A total of 8 AA-exposed
      workers and 36 non-exposed workers were recruited. Pre-shift and post-shift urine
      samples were collected from the exposed group in parallel with personal sampling
      for eight consecutive days and from the control group on day 1 of the study.
      Urinary N7-GAG and the mercapturic acids of AA and GA, namely N-acetyl-S-(2
      carbamoylethyl)-L-cysteine (AAMA) and N-(R,S)-acetyl-S-(1-carbamoyl-2
      hydroxyethyl)-L-cysteine (GAMA) were analyzed using on-line solid phase
      extraction-liquid chromatography-electrospray ionization/tandem mass spectrometry
      methods. We found that N7-GAG levels in urine were significantly higher in
      exposed workers than in controls and that N7-GAG level correlated positively with
      AAMA and GAMA levels. Results from this study showed that AAMA and GAMA possibly
      remain the more preferred biomarkers of AA exposure and that N7-GAG levels could
      be elevated by occupational exposures to AA and serve as a biomarker of AA
      induced genotoxicity for epidemiological studies.

PMID- 29463905
TI  - IBD: Functional characterization of an IBD risk gene.

PMID- 29463904
TI  - Gut microbiota: Beyond metagenomics, metatranscriptomics illuminates microbiome
      functionality in IBD.

PMID- 29463906
TI  - Noninvasive imaging biomarker assessment of liver fibrosis by elastography in
      NAFLD.
AB  - NAFLD is a global epidemic. The prevalence of NAFLD is 20-30% in North America,
      northern Europe, Australia, Japan, India and China. It is crucial that patients
      with NAFLD receive an assessment for their risk of advanced fibrosis, which
      increases the risk of hepatocellular carcinoma and other complications of
      cirrhosis. Risk stratification that is efficient, cost-effective, patient-centred
      and evidence-based is one of the most important issues facing clinicians who care
      for those with liver disease. Given patients' preference to avoid liver biopsy,
      noninvasive alternatives to assess liver fibrosis are in high demand. The most
      accurate noninvasive methods are based on liver elastography. Research on these
      techniques - which include vibration-controlled transient elastography (VCTE),
      magnetic resonance elastography (MRE), shear-wave elastography and acoustic
      radiation force impulse - has proliferated. Unfortunately, the literature has not
      kept pace with clinical practice. There is limited guidance for how clinicians
      should anticipate and manage the pitfalls of these tests. Furthermore, guidance
      is unavailable for clinicians regarding the optimal incorporation of VCTE, MRE or
      the emerging elastographic techniques into their clinical strategy, particularly
      for patients with NAFLD. In this Review, we summarize the available evidence,
      highlight gaps to address in further research and explore optimization of these
      techniques in clinical practice.

PMID- 29463908
TI  - Neural responses to cues paired with methamphetamine in healthy volunteers.
AB  - Drug cues, or conditioned responses to stimuli paired with drugs, are widely
      believed to promote drug use. The acquisition of these conditioned responses has
      been well characterized in laboratory animals: neutral stimuli paired with drugs
      elicit conditioned responses resembling the motivational and incentive properties
      of the drug itself. However, few studies have examined acquisition of
      conditioning, or the nature of the conditioned response, in humans. In this
      study, we used fMRI to examine neural responses to stimuli that had been paired
      with methamphetamine or placebo in healthy young adults. Participants first
      underwent four conditioning sessions in which visual-auditory stimuli were paired
      with either methamphetamine (20 mg, oral) or placebo. Then on a drug-free test
      day, the stimuli were presented during an fMRI scan to assess neural responses to
      the stimuli. We hypothesized that the stimuli would elicit drug-like brain
      activity, especially in regions related to reward. Instead, we found that the
      methamphetamine-paired stimuli, compared to placebo-paired stimuli, produced
      greater activation in regions related to visual and auditory processing,
      consistent with the drug's unconditioned effects on sensory processing. This is
      the first study to demonstrate conditioned neural responses to drug-paired
      stimuli after just two pairings of methamphetamine in healthy adults. The study
      also illustrates that conditioned responses may develop to unexpected components
      of the drug's effects.

PMID- 29463909
TI  - The effects of 5-hydroxytryptophan on attention and central serotonin
      neurochemistry in the rhesus macaque.
AB  - Psychiatric disorders, particularly depression and anxiety, are often associated
      with impaired serotonergic function. However, serotonergic interventions yield
      inconsistent effects on behavioral impairments. To better understand serotonin's
      role in these pathologies, we investigated the role of serotonin in a behavior
      frequently impaired in depression and anxiety, attention. In this study, we used
      a quantitative, repeated, within-subject, design to test how L-5
      hydroxytryptophan (5-HTP), the immediate serotonin precursor, modulates central
      serotoninergic function and attention in macaques. We observed that intramuscular
      5-HTP administration increased cisternal cerebrospinal fluid (CSF) 5-HTP and
      serotonin. In addition, individuals' baseline looking duration, during saline
      sessions, predicted the direction and magnitude in which 5-HTP modulated
      attention. We found that 5-HTP decreased looking duration in animals with high
      baseline attention, but increased looking duration in low baseline attention
      animals. Furthermore, individual differences in 5-HTP's effects were also
      reflected in how engaged individuals were in the task and how they allocated
      attention to salient facial features-the eyes and mouth-of stimulus animals.
      However, 5-HTP constricted pupil size in all animals, suggesting that the bi
      directional effects of 5-HTP cannot be explained by serotonin-mediated changes in
      autonomic arousal. Critically, high and low baseline attention animals exhibited
      different baseline CSF concentrations of 5-HTP and serotonin, an index of
      extracellular functionally active serotonin. Thus, our results suggest that
      baseline central serotonergic functioning may underlie and predict variation in
      serotonin's effects on cognitive operation. Our findings may help inform
      serotonin's role in psychopathology and help clinicians predict how serotonergic
      interventions will influence pathologies.

PMID- 29463907
TI  - Acid and the basis for cellular plasticity and reprogramming in gastric repair
      and cancer.
AB  - Subjected to countless daily injuries, the stomach still functions as a
      remarkably efficient digestive organ and microbial filter. In this Review, we
      follow the lead of the earliest gastroenterologists who were fascinated by the
      antiseptic and digestive powers of gastric secretions. We propose that it is
      easiest to understand how the stomach responds to injury by stressing the central
      role of the most important gastric secretion, acid. The stomach follows two basic
      patterns of adaptation. The superficial response is a pattern whereby the surface
      epithelial cells migrate and rapidly proliferate to repair erosions induced by
      acid or other irritants. The stomach can also adapt through a glandular response
      when the source of acid is lost or compromised (that is, the process of oxyntic
      atrophy). We primarily review the mechanisms governing the glandular response,
      which is characterized by a metaplastic change in cellular differentiation known
      as spasmolytic polypeptide-expressing metaplasia (SPEM). We propose that the
      stomach, like other organs, exhibits marked cellular plasticity: the glandular
      response involves reprogramming mature cells to serve as auxiliary stem cells
      that replace lost cells. Unfortunately, such plasticity might mean that the
      gastric epithelium undergoes cycles of differentiation and de-differentiation
      that increase the risk of accumulating cancer-predisposing mutations.

PMID- 29463910
TI  - Several behavioral traits relevant for alcoholism are controlled by gamma2
      subunit containing GABAA receptors on dopamine neurons in mice.
AB  - The risk factors for developing alcohol addiction include impulsivity, high
      sensitivity to the rewarding action of ethanol, and low sensitivity to its
      sedative and intoxicating effects. Genetic variation in GABAA receptor subunits,
      including the gamma2 subunit (Gabrg2), affects the risk for developing
      alcoholism. Alcohol directly potentiates GABAA receptors and activates the
      mesolimbic dopamine system. Here, we deleted Gabrg2 selectively in dopamine cells
      of adult mice. The deletion resulted in elevated firing of dopamine neurons and
      made them less sensitive to drugs acting at GABAA receptors. At the behavioral
      level, the deletion increased exploratory behavior and augmented both correct and
      incorrect responding in the go/no-go task, a test often used to assay the
      response inhibition component of impulsivity. In addition, conditioned place
      preference to alcohol, but not to cocaine or morphine, was increased. Ethanol
      induced locomotor activation was enhanced in the mice lacking Gabrg2 on
      dopaminergic cells, whereas the sedative effect of alcohol was reduced. Finally,
      the alcohol drinking, but not the alcohol preference, at a high concentration was
      increased in the mutant mice. In summary, deletion of Gabrg2 on dopamine cells
      induced several behavioral traits associated with high risk of developing
      alcoholism. The findings suggest that mice lacking Gabrg2 on dopaminergic cells
      could be used as models for individuals at high risk for developing alcoholism
      and that GABAA receptors on dopamine cells are protective against the development
      of excessive alcohol drinking.

PMID- 29463911
TI  - Disruption of lipid-raft localized Galphas/tubulin complexes by antidepressants:
      a unique feature of HDAC6 inhibitors, SSRI and tricyclic compounds.
AB  - Current antidepressant therapies meet with variable therapeutic success and there
      is increasing interest in therapeutic approaches not based on monoamine
      signaling. Histone deacetylase 6 (HDAC6), which also deacetylates alpha-tubulin
      shows altered expression in mood disorders and HDAC6 knockout mice mimic
      traditional antidepressant treatments. Nonetheless, a mechanistic understanding
      for HDAC6 inhibitors in the treatment of depression remains elusive. Previously,
      we have shown that sustained treatment of rats or glioma cells with several
      antidepressants translocates Galphas from lipid rafts toward increased
      association with adenylyl cyclase (AC). Concomitant with this is a sustained
      increase in cAMP production. While Galphas modifies microtubule dynamics, tubulin
      also acts as an anchor for Galphas in lipid-rafts. Since HDAC-6 inhibitors
      potentiate alpha-tubulin acetylation, we hypothesize that acetylation of alpha
      tubulin disrupts tubulin-Galphas raft-anchoring, rendering Galphas free to
      activate AC. To test this, C6 Glioma (C6) cells were treated with the HDAC-6
      inhibitor, tubastatin-A. Chronic treatment with tubastatin-A not only increased
      alpha-tubulin acetylation but also translocated Galphas from lipid-rafts, without
      changing total Galphas. Reciprocally, depletion of alpha-tubulin acetyl
      transferase-1 ablated this phenomenon. While escitalopram and imipramine also
      disrupt Galphas/tubulin complexes and translocate Galphas from rafts, they evoke
      no change in tubulin acetylation. Finally, two indicators of downstream cAMP
      signaling, cAMP response element binding protein phosphorylation (pCREB) and
      expression of brain-derived-neurotrophic-factor (BDNF) were both elevated by
      tubastatin-A. These findings suggest HDAC6 inhibitors show a cellular profile
      resembling traditional antidepressants, but have a distinct mode of action. They
      also reinforce the validity of antidepressant-induced Galphas translocation from
      lipid-rafts as a biosignature for antidepressant response that may be useful in
      the development of new antidepressant compounds.

PMID- 29463912
TI  - Preclinical evaluation of the kappa-opioid receptor antagonist CERC-501 as a
      candidate therapeutic for alcohol use disorders.
AB  - Prior work suggests a role of kappa-opioid signaling in the control of alcohol
      drinking, in particular when drinking is escalated due to alcohol-induced long
      term neuroadaptations. Here, we examined the small molecule selective kappa
      antagonist CERC-501 in rat models of alcohol-related behaviors, with the
      objective to evaluate its potential as a candidate therapeutic for alcohol use
      disorders. We first tested the effect of CERC-501 on acute alcohol withdrawal
      induced anxiety-like behavior. CERC-501 was then tested on basal as well as
      escalated alcohol self-administration induced by 20% alcohol intermittent access.
      Finally, we determined the effects of CERC-501 on relapse to alcohol seeking
      triggered by both stress and alcohol-associated cues. Control experiments were
      performed to confirm the specificity of CERC-501 effects on alcohol-related
      behaviors. CERC-501 reversed anxiety-like behavior induced by alcohol withdrawal.
      It did not affect basal alcohol self-administration but did dose-dependently
      suppress self-administration that had escalated following long-term intermittent
      access to alcohol. CERC-501 blocked relapse to alcohol seeking induced by stress,
      but not when relapse-like behavior was triggered by alcohol-associated cues. The
      effects of CERC-501 were observed in the absence of sedative side effects and
      were not due to effects on alcohol metabolism. Thus, in a broad battery of
      preclinical alcohol models, CERC-501 has an activity profile characteristic of
      anti-stress compounds. Combined with its demonstrated preclinical and clinical
      safety profile, these data support clinical development of CERC-501 for alcohol
      use disorders, in particular for patients with negatively reinforced, stress
      driven alcohol seeking and use.

PMID- 29463913
TI  - Impact of co-administration of oxycodone and smoked cannabis on analgesia and
      abuse liability.
AB  - Cannabinoids combined with opioids produce synergistic antinociceptive effects,
      decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing
      effects) in laboratory animals. Although pain patients report greater analgesia
      when cannabis is used with opioids, no placebo-controlled studies have assessed
      the direct effects of opioids combined with cannabis in humans or the impact of
      the combination on abuse liability. This double-blind, placebo-controlled, within
      subject study determined if cannabis enhances the analgesic effects of low dose
      oxycodone using a validated experimental model of pain and its effects on abuse
      liability. Healthy cannabis smokers (N = 18) were administered oxycodone (0, 2.5,
      and 5.0 mg, PO) with smoked cannabis (0.0, 5.6% Delta9 tetrahydrocannabinol
      [THC]) and analgesia was assessed using the Cold-Pressor Test (CPT). Participants
      immersed their hand in cold water (4  degrees C); times to report pain (pain
      threshold) and withdraw the hand from the water (pain tolerance) were recorded.
      Abuse-related effects were measured and effects of oxycodone on cannabis self
      administration were determined. Alone, 5.0 mg oxycodone increased pain threshold
      and tolerance (p <= 0.05). Although active cannabis and 2.5 mg oxycodone alone
      failed to elicit analgesia, combined they increased pain threshold and tolerance
      (p <= 0.05). Oxycodone did not increase subjective ratings associated with
      cannabis abuse, nor did it increase cannabis self-administration. However, the
      combination of 2.5 mg oxycodone and active cannabis produced small, yet
      significant, increases in oxycodone abuse liability (p <= 0.05). Cannabis
      enhances the analgesic effects of sub-threshold oxycodone, suggesting synergy,
      without increases in cannabis's abuse liability. These findings support future
      research into the therapeutic use of opioid-cannabinoid combinations for pain.

PMID- 29463914
TI  - Oxidation-stable amine-containing adsorbents for carbon dioxide capture.
AB  - Amine-containing solids have been investigated as promising adsorbents for CO2
      capture, but the low oxidative stability of amines has been the biggest hurdle
      for their practical applications. Here, we developed an extra-stable adsorbent by
      combining two strategies. First, poly(ethyleneimine) (PEI) was functionalized
      with 1,2-epoxybutane, which generates tethered 2-hydroxybutyl groups. Second,
      chelators were pre-supported onto a silica support to poison p.p.m.-level metal
      impurities (Fe and Cu) that catalyse amine oxidation. The combination of these
      strategies led to remarkable synergy, and the resultant adsorbent showed a minor
      loss of CO2 working capacity (8.5%) even after 30 days aging in O2-containing
      flue gas at 110  degrees C. This corresponds to a ~50 times slower deactivation
      rate than a conventional PEI/silica, which shows a complete loss of CO2 uptake
      capacity after the same treatment. The unprecedentedly high oxidative stability
      may represent an important breakthrough for the commercial implementation of
      these adsorbents.

PMID- 29463915
TI  - Opportunistic random searcher versus intentional search image user.
AB  - We consider two types of optimal foragers: a random searcher and a search image
      user. A search image user can find its desired prey with higher and undesired
      prey with lower probability than a random searcher. Our model considers the
      density-dependent travelling time and the time duration of reproduction
      (oviposition). In the framework of optimal foraging theory for one predator-two
      prey systems, we find that there are ranges of prey densities in which the search
      image user has a higher net energy intake, and there are other ranges of prey
      densities in which the random searcher has higher net energy intake. The damsel
      bug Nabis pseudoferus Remane (Hemiptera: Nabidae) is a generalist predator rather
      than an omnivore. This species has a wide range of arthropod prey (predominantly
      insects and mites). Several aspects of the biology of this species have been
      studied, especially its cannibalistic behaviour, which is a quite important
      feature because N. pseudoferus is often used as a biological control agent
      against lepidopteran pests in greenhouse crops. Experimentally, we found that
      Nabis is a search image user in the above sense.

PMID- 29463916
TI  - Evaluating feasibility and accuracy of non-invasive tests for nonalcoholic fatty
      liver disease in severe and morbid obesity.
AB  - INTRODUCTION: In obese individuals, nonalcoholic fatty liver disease (NAFLD) is
      common but often goes undiagnosed, and therefore untreated. The presence of
      significant fibrosis is a key determinant of NAFLD progression, and liver
      steatosis has substantial cardiovascular implications. We aimed to determine the
      diagnostic accuracy of common noninvasive diagnostic tests for steatosis and
      fibrosis in the obese. METHODS: We recruited 182 severely and morbidly obese
      individuals undergoing bariatric surgery (age 44 +/- 12 years, body mass index
      45.1 +/- 8.3 kg/m2). Medical history, blood tests and liver biopsy were taken on
      the day of surgery. Serum steatosis and fibrosis scores were calculated. In a
      subgroup of patients, transient elastography with controlled attenuation
      parameter (TE/CAP) (n = 82) and proton magnetic resonance spectroscopy (1H-MRS)
      (n = 49) were performed. RESULTS: 1H-MRS had excellent diagnostic accuracy for
      steatosis, with strong correlation to steatosis (r = 0.647, p < 0.001), good
      AUROC (0.852, p = 0.001), sensitivity (81.3%) and specificity (87.5%). However,
      due to low feasibility in this cohort (65.3% success), this was substantially
      decreased with intention-to-diagnose analysis (sensitivity 50.0%, specificity
      60.9%). CAP had good feasibility (80.5%), and performed better in intention-to
      diagnose analysis (AUROC 0.688, sensitivity 84.8%, specificity 47.2%). Serum
      steatosis scores performed poorly, with comparable accuracy to ALT. For
      significant fibrosis, TE had the best accuracy (AUROC 0.903, p = 0.007), which
      remained reasonable after intention-to-diagnose analysis (sensitivity 100%,
      specificity 59.0%). A combination approach using CAP with ALT for steatosis and
      TE with Forn index for fibrosis yielded reasonable overall accuracy. CONCLUSIONS:
      1H-MRS and TE/CAP had greatest accuracy for NAFLD-related steatosis and fibrosis.
      Failure rates in obesity significantly diminished diagnostic ability. Use of a
      combination of serum and imaging tests improved overall feasibility of assessment
      and diagnostic accuracy in obese individuals.

PMID- 29463918
TI  - Sex differences in the metabolic effects of diet-induced obesity vary by age of
      onset.
AB  - Sex differences in the effect of diet-induced obesity (DIO) have been reported in
      juvenile mice. However, thorough side by side comparisons of the effects of DIO
      in males and females at different ages of onset have yet to be examined. We
      hypothesized that aged females would lose their protection, relative to males,
      from the effects of DIO. We examined the effect of DIO on body weight and glucose
      tolerance in juvenile, young adult, and middle-aged male and female mice. Our
      data show DIO in juvenile mice causes a greater increase in body weight and
      greater impairment in glucose tolerance in males than females. However, if the
      diet is initiated in young adult mice, these sex differences are absent. Further,
      if the diet is initiated in middle-aged mice, the sex difference is reversed, and
      females gain more weight and have greater impairment in glucose tolerance than
      males. Our data show that sex differences in the effect of DIO vary by age of
      onset; thus highlighting the importance of both age and sex as biological
      variables in DIO research.

PMID- 29463917
TI  - Infant temperament and parent use of food to soothe predict change in weight-for
      length across infancy: early risk factors for childhood obesity.
AB  - OBJECTIVES: Greater weight gain in infancy is a risk factor for childhood
      obesity. The present study examined the interaction between infant temperament
      and parent use of food to soothe infant distress (FTS) as predictors of weight
      gain across the first 2 years of life. SUBJECTS/METHODS: A total of 160 mother
      infant dyads were recruited into a longitudinal study. Infant temperament was
      assessed by parents through a questionnaire (surgency, negativity) and by
      observer ratings (surgency, irritability) during a laboratory visit when infants
      were 6 months old. Parents also completed a 3-day infant cry diary when their
      children were 6 months of age to assess when they used food in response to infant
      cry/fuss bouts. Infant weight/length was measured in the lab at 6 and 18 months.
      Multiple regressions were run to test the moderating effect of FTS on weight
      gain. RESULTS: Significant interactions were revealed for both measures of
      surgency and parent FTS in predicting weight gain. Surgent infants whose parents
      had a greater tendency to use FTS had greater weight-for-length gain in 1 year
      than if their parents tended to use less FTS. The interaction between observer
      ratings of irritability and parent FTS was also significant but in an unexpected
      direction. CONCLUSIONS: The findings point to the role of temperament,
      specifically surgency, in weight gain during infancy, but only if their parents
      used FTS. Surgency may have evoked this feeding practice that increased their
      health risk.

PMID- 29463919
TI  - Sex-dimorphic acceleration of pericardial, subcutaneous, and plasma lipid
      increase in offspring of poorly nourished baboons.
AB  - Developmental programming by reduced maternal nutrition alters function in
      multiple offspring physiological systems, including lipid metabolism. We have
      shown that intrauterine growth restriction (IUGR) leads to offspring
      cardiovascular dysfunction with an accelerated aging phenotype in our nonhuman
      primate, baboon model. We hypothesized age-advanced pericardial fat and blood
      lipid changes. In pregnancy and lactation, pregnant baboons ate ad lib (control)
      or 70% ad lib diet (IUGR). We studied baboon offspring pericardial lipid
      deposition with magnetic resonance imaging at 5-6 years (human equivalent 20-24
      years), skinfold thickness, and serum lipid profile at 8-9 years (human
      equivalent 32-36 years), comparing values with a normative life-course baboon
      cohort, 4-23 years. Increased pericardial fat deposition occurred in IUGR males
      but not females. Female but not male total cholesterol, low-density lipoprotein,
      and subcutaneous fat were increased with a trend of triglycerides increase. When
      comparing IUGR changes to values in normal older baboons, the increase in male
      apical pericardial fat was equivalent to advancing age by 6 years and the
      increase in female low-density lipoprotein to an increase of 3 years. We conclude
      that reduced maternal diet accelerates offspring lipid changes in a sex-dimorphic
      manner. The interaction between programming and accelerated lipogenesis warrants
      further investigation.

PMID- 29463920
TI  - Re: "Widespread prevalence of a CREBRF variant amongst Maori and Pacific children
      is associated with weight and height in early childhood".

PMID- 29463921
TI  - Accelerating efforts to end TB.

PMID- 29463922
TI  - Clinical challenges in antimicrobial resistance.

PMID- 29463923
TI  - Another twist on nitrogenases.

PMID- 29463924
TI  - CRISPRs from scratch.

PMID- 29463926
TI  - TB diagnosis from the Dark Ages to fluorescence.

PMID- 29463925
TI  - Disulfide bond formation in prokaryotes.
AB  - Interest in protein disulfide bond formation has recently increased because of
      the prominent role of disulfide bonds in bacterial virulence and survival. The
      first discovered pathway that introduces disulfide bonds into cell envelope
      proteins consists of Escherichia coli enzymes DsbA and DsbB. Since its discovery,
      variations on the DsbAB pathway have been found in bacteria and archaea, probably
      reflecting specific requirements for survival in their ecological niches. One
      variation found amongst Actinobacteria and Cyanobacteria is the replacement of
      DsbB by a homologue of human vitamin K epoxide reductase. Many Gram-positive
      bacteria express enzymes involved in disulfide bond formation that are similar,
      but non-homologous, to DsbAB. While bacterial pathways promote disulfide bond
      formation in the bacterial cell envelope, some archaeal extremophiles express
      proteins with disulfide bonds both in the cytoplasm and in the extra-cytoplasmic
      space, possibly to stabilize proteins in the face of extreme conditions, such as
      growth at high temperatures. Here, we summarize the diversity of disulfide-bond
      catalysing systems across prokaryotic lineages, discuss examples for
      understanding the biological basis of such systems, and present perspectives on
      how such systems are enabling advances in biomedical engineering and drug
      development.

PMID- 29463927
TI  - Pandemic preparedness and forecast.

PMID- 29463928
TI  - fNIRS Optodes' Location Decider (fOLD): a toolbox for probe arrangement guided by
      brain regions-of-interest.
AB  - The employment of functional near-infrared spectroscopy (fNIRS) as a method of
      brain imaging has increased over the last few years due to its portability, low
      cost and robustness to subject movement. Experiments with fNIRS are designed in
      the face of a limited number of sources and detectors (optodes) to be positioned
      on selected portion(s) of the scalp. The optodes locations represent an
      expectation of assessing cortical regions relevant to the experiment's
      hypothesis. However, this translation process remains a challenge for fNIRS
      experimental design. In the present study, we propose an approach that
      automatically decides the location of fNIRS optodes from a set of predefined
      positions with the aim of maximizing the anatomical specificity to brain regions
      of-interest. The implemented method is based on photon transport simulations on
      two head atlases. The results are compiled into the publicly available "fNIRS
      Optodes' Location Decider" (fOLD). This toolbox is a first-order approach to
      bring the achieved advancements of parcellation methods and meta-analyses from
      functional magnetic resonance imaging to more precisely guide the selection of
      optode positions for fNIRS experiments.

PMID- 29463929
TI  - Metabolism: A metabolic switch of fate.

PMID- 29463930
TI  - Gene expression: Developmental enhancers in action.

PMID- 29463931
TI  - Moving towards a molecular taxonomy of autoimmune rheumatic diseases.
AB  - This corrects the article DOI: 10.1038/nrrheum.2017.220.

PMID- 29463932
TI  - Cell-based Biological Pacemakers: Progress and Problems.
AB  - The number of permanent pacemaker implantations has been increasing due to the
      aging of populations worldwide and the increase in the numbers of patients with
      heart diseases. Commercially available mechanical pacemakers are very useful but
      still have some problems including short battery life, a risk of infection, the
      absence of physiological autonomic responsiveness, metal allergy, and electronic
      interference. A biological pacemaker may resolve these problems and regenerate
      the cardiac pacemaker. Cell-based therapy and gene therapy have been addressed
      with the goal of solving the challenges of biological pacemaker. However, the
      clinical application of a biological pacemaker has not yet been realized. Here we
      discuss the types of cells that can be used for a biological pacemaker and the
      problems that remain regarding the clinical applications of cell-based therapy.

PMID- 29463933
TI  - A Randomized Controlled Trial of Short-term Toe Resistance Training to Improve
      Toe Pinch Force in Patients with Type 2 Diabetes.
AB  - Resistance training is effective against type 2 diabetes (T2DM), but the effect
      of resistance training on toe pinch force (TPF) is unknown. Here we investigated
      the effect of short-term toe resistance training on TPF in patients with T2DM, in
      a prospective, parallel-group, single-blind, randomized controlled trial. Twelve
      patients with T2DM who were hospitalized to improve glycemic control were
      enrolled. The patients were randomly allocated to the intervention (n=6) and
      control (n=6) groups. The intervention group performed traditional aerobic
      exercise and 4 newly developed toe-resistance training exercises. The control
      group performed aerobic exercise only. After 2 weeks of the exercise intervention
      program, we evaluated anthropometric parameters, clinical parameters, motor
      function, and muscle parameters in each patient. After the exercise intervention
      program, the TPF and toe muscle quality, isometric knee extension force, and knee
      muscle quality were significantly higher in the intervention group compared to
      the control group. Two weeks of toe-resistance training significantly increased
      the TPF in the T2DM patients. Toe resistance training is thus recommended in
      clinical practice for patients with T2DM.

PMID- 29463934
TI  - Total Hip Arthroplasty for Patients with Residual Poliomyelitis at a Mean Eight
      Years of Follow-up.
AB  - In patients with poliomyelitis, degenerative arthritis of the hip may be
      encountered in the paralytic or normal contralateral limb because of leg length
      discrepancy, pelvic obliquity, or severe deformities of the affected hip.
      Although total hip arthroplasty (THA) is one of the most common orthopedic
      procedures, there are few reports of THA in adult patients with residual
      poliomyelitis. From March 2001 to January 2011, 5 patients with residual
      poliomyelitis (6 hips) underwent THA using uncemented implants at our hospital.
      We retrospectively evaluated the Japanese Orthopedic Association (JOA) hip rating
      score, complications, and radiographs. All five patients' follow-up information
      was available: 4.5 years minimum, 8.4 years average, range 4.5-15 years. Surgery
      was done at the same side of the paralytic limb in 2 hips and contralateral to
      the paralytic limb in four hips. All patients had pain relief and improvement in
      function; JOA hip rating score improved significantly from the mean of 45
      preoperatively to 78 at the last follow-up (p=0.0313). There was no loosening or
      osteolysis in this series, and no cases of dislocation, infection or nerve palsy.
      These findings can contribute to decisions regarding treatment for arthritic hips
      in adults with residual poliomyelitis.

PMID- 29463935
TI  - A20 (TNFAIP3) Alterations in Primary Intestinal Diffuse Large B-cell Lymphoma.
AB  - The gastrointestinal (GI) tract is the most frequently involved site of
      extranodal non-Hodgkin lymphomas, and diffuse large B-cell lymphoma (DLBCL) is
      the most common subtype occurring in the GI tract. TNFAIP3 (A20) genetic
      alterations were reported to be involved in DLBCL's pathogenesis and a portion of
      GI-DLBCL cases harbor this alteration. However, the frequency and
      clinicopathological relations focusing on small and large intestinal DLBCL are
      unclear. Here, we examined A20 deletion and protein expression and analyzed the
      clinicopathological features of 52 cases of primary intestinal DLBCL. The most
      frequently involved site was the ileocecal region (75%), followed by small bowel
      (13.5%) and large intestine. Immunohistochemically, the ileocecal cases expressed
      BCL6 (p=0.027) and MUM1 (p=0.0001) significantly more frequently than the small
      intestinal cases. Six of 47 cases (13%) had A20 heterozygous deletion, whereas
      all 6 heterozygously deleted cases had detectable A20 protein expression. In
      summary, A20 abnormality was less prevalent among intestinal DLBCLs with some
      discordancy between gene deletion and protein expression. Although the A20
      alteration status did not affect any clinicopathological characteristics in this
      series, further studies exploring alterations of A20 and other NF-kappaB
      components in primary intestinal DLBCL are needed.

PMID- 29463936
TI  - Relationship between Social Participation, Physical Activity and Psychological
      Distress in Apparently Healthy Elderly People: A Pilot Study.
AB  - Few studies examined the relationship between social participation, physical
      activity and psychological distress in elderly people. Here we examined these
      relationships in apparently healthy elderly people. After exclusion of subjects
      who dropped out or did not meet enrollment criteria, the data of 86 subjects
      (apparently healthy elderly embers at a college health club; 25 males, 61
      females) from July 20 to September 10, 2016 were used. We evaluated each
      subject's psychological distress using the K6 questionnaire, social participation
      by a self-completed questionnaire, and physical activity level by a triaxial
      accelerometer (7 consecutive days). The K6 scores were significantly correlated
      with social participation in the total series and the women. The K6 scores of the
      subjects who had engaged in social participation (1.847+/-2.231) were
      significantly lower (better) than those of the subjects who had not (6.714+/
      5.014). Both exercise limitation and social participation were significant
      predictors of the K6 scores. Our findings indicate that psychological distress in
      apparently healthy elderly people is not associated with physical activity, but
      is associated with social participation. Our results demonstrate that in healthy
      elderly people, participating in a social activity can help improve psychological
      distress.

PMID- 29463937
TI  - Results of a Treat-and-Eextend Regimen of Intravitreal Ranibizumab Injection for
      Macular Edema due to Branch Retinal Vein Occlusion.
AB  - To investigate the effectiveness of a treat-and-extend regimen (TAE) of
      intravitreal ranibizumab injections (IVR) for macular edema (ME) due to branch
      retinal vein occlusion (BRVO). We retrospectively examined 35 eyes of 35 patients
      with ME due to BRVO who underwent TAE for 1 year. Patients whose treatment
      interval extended to 12 weeks were switched to a pro re nata regimen (PRN; TAE to
      PRN group), while TAE was continued for patients whose treatment interval was
      less than 12 weeks (continued TAE group). Changes in best-corrected visual acuity
      (BCVA), central retinal thickness (CRT), and predictive factors for inclusion in
      the TAE to PRN group were analyzed. BCVA and CRT both improved significantly at 1
      year compared with baseline (p<0.001). Sixteen eyes (45.7%) were included in the
      TAE to PRN group, while 19 eyes (54.3%) were included in the continued TAE group.
      BCVA in the TAE to PRN group was significantly better than that in the continued
      TAE group at 1 year (p=0.047). BCVA at baseline and macular BRVO were significant
      predictive factors for inclusion in the TAE to PRN group. TAE was effective for
      improving BCVA and CRT. The TAE to PRN group showed significantly better
      prognosis.

PMID- 29463938
TI  - Transcatheter Arterial Chemoembolization to Reduce Size of Hepatocellular
      Carcinoma before Radiofrequency Ablation.
AB  - Transcatheter arterial chemoembolization (TACE) is often performed before
      radiofrequency ablation (RFA) for the treatment of early-stage hepatocellular
      carcinoma (HCC). TACE prior to RFA can expand the ablated area and reduce the
      tumor size, facilitating complete ablation. However, the factors correlated with
      size reduction remain uncertain. The aim of this study was to identify the
      factors associated with size reduction by TACE and develop a formula to predict
      the reduction rate. A total of 100 HCC patients treated with TACE followed by RFA
      at least 20 days later were enrolled. The tumor size was measured at the time of
      TACE and RFA, and correlations between the reduction rate and 13 clinical factors
      were examined. A formula to predict the reduction rate was built using the
      factors obtained by the analysis. Reduction in the tumor size was observed in 69
      nodules, and the median reduction rate was 16.2%. A multivariate regression
      analysis revealed that a large tumor size (p< 0.01) and a long interval between
      the therapies (p= 0.01) were factors for a high tumor reduction rate, with tumor
      size more strongly related to the degree of reduction. A size reduction of more
      than 10% can be expected by waiting 20 days after TACE when the size of the tumor
      at TACE is over 25 mm in diameter. The tumor size.

PMID- 29463939
TI  - The Usefulness of Readout-Segmented Echo-Planar Imaging (RESOLVE) for Bio-phantom
      Imaging Using 3-Tesla Clinical MRI.
AB  - Readout-segmented echo-planar imaging (RESOLVE) is a multi-shot echo-planar
      imaging (EPI) modality with k-space segmented in the readout direction. We
      investigated whether RESOLVE decreases the distortion and artifact in the phase
      direction and increases the signal-to-noise ratio (SNR) in phantoms image taken
      with 3-tesla (3T) MRI versus conventional EPI. We used a physiological saline
      phantom and subtraction mapping and observed that RESOLVE's SNR was higher than
      EPI's. Using RESOLVE, the combination of a special-purpose coil and a large-loop
      coil had a higher SNR compared to using only a head/neck coil. RESOLVE's image
      distortioas less than EPI's. We used a 120 mM polyethylene glycol phantom to
      examine the phase direction artifact.vThe range where the artifact appeared in
      the apparent diffusion coefficient (ADC) image was shorter with RESOLVE compared
      to EPI. We used RESOLVE to take images of a Jurkat cell bio-phantom: the cell
      region ADC was 856*10-6mm2/sec and the surrounding physiological saline-region
      ADC was 2,951*10-6mm2/sec. The combination of RESOLVE and the 3T clinical MRI
      device reduced image distortion and improved SNR and the identification of
      accurate ADC values due to the phase direction artifact reduction. This
      combination is useful for obtaining accurate ADC values of bio-phantoms.

PMID- 29463940
TI  - Slow Fetal Heart Rate before Miscarriage in the Early First Trimester Predicts
      Fetal Aneuploidy in Women with Recurrent Pregnancy Loss.
AB  - Establishing whether miscarriages result from fetal aneuploidy or other factors
      is important for treating recurrent pregnancy loss. We examined the relationship
      between fetal heart rate (FHR) before miscarriage in the early first trimester
      and fetal karyotype, analyzing 223 pregnant women with recurrent pregnancy loss.
      Among the pregnancies, 110 resulted in live births regarded as normal karyotype
      (the Norm-group). The other 113 pregnancies ended in miscarriage, and we
      categorized them into groups based on fetal karyotype, determined by chorionic
      villus sampling: the Misc-NK (normal karyotype) group, n=35 euploid cases; the
      Misc-CA1 (chromosomal abnormality) group, n=18 cases of aneuploidy with trisomies
      13/18/21, Turner's syndrome, or Klinefelter's syndrome; and the Misc-CA2
      subgroup, n=60 cases of other aneuploidies excluding those in the Misc-CA1 group.
      We compared the groups' regression line slopes and intercepts for FHR by an
      analysis of covariance. The FHRs of the Norm, Misc-NK and Misc-CA1 groups
      increased from 36 to 49 days after fertilization, but did not significantly
      differ across these groups. The Misc-CA2 group's FHR did not increase and
      significantly differed from the other three groups (p<0.01). These results
      suggest that the absence of an increase in FHR in early pregnancy may indicate
      the presence of chromosomal abnormalities causing miscarriage.

PMID- 29463941
TI  - Differences in Risk Factors for Rotator Cuff Tears between Elderly Patients and
      Young Patients.
AB  - It has been unclear whether the risk factors for rotator cuff tears are the same
      at all ages or differ between young and older populations. In this study, we
      examined the risk factors for rotator cuff tears using classification and
      regression tree analysis as methods of nonlinear regression analysis. There were
      65 patients in the rotator cuff tears group and 45 patients in the intact rotator
      cuff group. Classification and regression tree analysis was performed to predict
      rotator cuff tears. The target factor was rotator cuff tears; explanatory
      variables were age, sex, trauma, and critical shoulder angle>=35 degrees . In the
      results of classification and regression tree analysis, the tree was divided at
      age 64. For patients aged>=64, the tree was divided at trauma. For patients
      aged<64, the tree was divided at critical shoulder angle>=35 degrees . The odds
      ratio for critical shoulder angle>=35 degrees  was significant for all ages
      (5.89), and for patients aged<64 (10.3) while trauma was only a significant
      factor for patients aged>=64 (5.13). Age, trauma, and critical shoulder angle>=35
      degrees  were related to rotator cuff tears in this study. However, these risk
      factors showed different trends according to age group, not a linear
      relationship.

PMID- 29463942
TI  - Spinal Extradural Arachnoid Cyst: Significance of Intrathecal Infusion after
      Fistula Closure.
AB  - The spinal extradural arachnoid cyst is a rare entity. Obtaining the correct
      diagnosis and detecting the fistula location are critical for providing effective
      treatment. A 41-year-old man had numbness in the soles of his feet for 2 years
      with accompanying gait disturbance, and a defecation disorder. Computed
      tomography myelography performed at another hospital revealed an epidural
      arachnoid cyst from Th11 to L2. He received a subarachnoid-cyst shunt at the
      rostral part of the cyst. However, his symptoms worsened and he was admitted to
      our hospital. Neuroradiological investigations revealed the correct location of
      the fistula at the level of Th12. We performed partial removal of the cyst wall
      with fistula closure via right hemilaminectomy of Th11 and 12. The complete
      closure of the fistula was confirmed by intrathecal infusion of artificial
      cerebrospinal fluid through the shunt tube. The shunt tube was removed with the
      sutures. The patient's symptoms improved, although numbness remained in his
      bilateral heels. There has been no recurrence in 15 months since the surgery.
      Fistula closure may work as a balanced therapeutic strategy for spinal extradural
      arachnoid cyst, and intrathecal cerebrospinal fluid infusion is useful for the
      confirmation of complete fistula closure.

PMID- 29463943
TI  - Tarsal Tunnel Syndrome Caused by a Schwannoma of the Posterior Tibial Nerve.
AB  - Schwannoma is the most common tumor of the peripheral nerve sheath. However,
      there have been few reports on schwannoma of the posterior tibial nerve causing
      tarsal tunnel syndrome. We report on a 60-year-old man with tarsal tunnel
      syndrome caused by a schwannoma of the posterior tibial nerve, which was first
      diagnosed as a ganglion cyst. After enucleation of this tumor, the patient was
      asymptomatic and had no related sequelae except for minor numbness in the plantar
      aspects of his digits. Although schwannoma of the posterior tibial nerve is rare,
      it should be considered even if a ganglion is clinically suspected.

PMID- 29463944
TI  - Laparoscopic Surgery for Small Bowel Obstruction due to Paracecal Hernia.
AB  - Internal hernia related to paracecal hernia is a rare disease and is difficult to
      confirm by preoperative diagnosis. We recently encountered a case of an 83-year
      old woman who had lower abdominal pain in her right quadrant. Based on physical
      findings and CT findings she was diagnosed as having small bowel obstruction by
      internal hernia around the cecum. She underwent emergency operation with
      laparoscopic surgery and was diagnosed with a paracecal hernia and treated
      laparoscopically. After we dissected the ventral wall of the hernia sac and
      enlarged the hernia orifice, we reduced the trapped small intestine into the
      abdominal space. We determined that the herniated portion of the small intestine
      was not necrotic and therefore did not resect it. Although paracecal hernia is a
      rare internal hernia, physicians should be aware of it as a differential
      diagnosis for small bowel obstruction because of its rapid progression to
      strangulation and necrosis. We highlight the importance of recognizing CT
      findings of paracecal internal hernia. Laparoscopy was effective both for making
      a definitive diagnosis and treating paracecal hernia with relatively little
      invasion.

PMID- 29463945
TI  - Traumatic Globe Luxation with Complete Optic Nerve Transection Caused by Heavy
      Object Compression.
AB  - Traumatic eyeball luxation is a rare clinical condition with a dramatic
      presentation. Here, we describe a unique case of traumatic globe luxation and
      complete optic nerve transection caused by heavy object compression. A 45-year
      old male automobile mechanic was injured when a truck slipped from its supports,
      crushing his head and face. On arrival, his right eyeball was obviously displaced
      anteriorly and he had no light perception. Computed tomography revealed complex
      frontal bone and facial fractures with underlying brain contusion in addition to
      complete transection of the right optic nerve. The patient was successfully
      treated using a multidisciplinary approach.

PMID- 29463946
TI  - Extensive Bilateral Patellar Tendon Ossification in a Spinal Cord Injury Patient.
AB  - This is the first report of extensive bilateral patellar tendon ossification
      occurring over a prolonged time after a unilateral knee injury. An 84-year-old
      Japanese man with a spinal cord injury caused by a burst fracture of the T12
      vertebra presented with a bony hard prominence on the left knee, which was
      injured in a traffic accident when he was 77 years old. Radiography revealed
      extensive ossification of the bilateral patellar tendons. We review the English
      literature with a focus on the localization of bilateral heterotopic ossification
      of the knee in patients who had a central nervous system injury.

PMID- 29463947
TI  - Randomized Controlled Trial of Epidural versus Patient-controlled Intravenous
      Analgesia for Postoperative Pain Control after Laparoscopic Gastrectomy.
AB  - Although epidural analgesia (EDA) is considered standard postoperative analgesia
      for open gastrectomy, it has been unclear whether EDA has benefits in
      laparoscopic gastrectomy (LG) because postoperative pain after a laparoscopic
      procedure is significantly reduced. We are conducting a two-arm, single-center,
      prospective randomized non-inferiority trial to evaluate the postoperative pain
      relief of patient-controlled intravenous analgesia (PCIA) compared to EDA. A
      total of 132 patients undergoing LG will be randomized to EDA and PCIA groups
      (n=64 each) for postoperative pain control. The primary endpoint is postoperative
      pain at 24 h after surgery. This study will clarify the optimal pain management
      after LG.

PMID- 29463948
TI  - MicroRNA-155-5p Overexpression in Peripheral Blood Mononuclear Cells of Chronic
      Lymphocytic Leukemia Patients Is a Novel, Independent Molecular Biomarker of Poor
      Prognosis.
AB  - MicroRNA-155-5p (miR-155-5p) is a proinflammatory, oncogenic miRNA, involved in
      various physiological processes, including hematopoiesis, immunity, inflammation,
      and cell lineage differentiation. It regulates important transcription factors,
      such as E2F2, hypoxia-inducible factor 1 (HIF1), and FOXO3. Recently, the
      dysregulation of miR-155-5p expression has been linked to chronic lymphocytic
      leukemia (CLL) pathogenesis. In this research study, we investigated the
      potential diagnostic and prognostic value of miR-155-5p in CLL. To achieve our
      goal, we isolated total RNA from peripheral blood mononuclear cells (PBMCs)
      collected from 88 CLL patients and 36 nonleukemic blood donors and performed
      polyadenylation of total RNA and reverse transcription. Next, we quantified miR
      155-5p levels using an in-house-developed real-time quantitative PCR method,
      before proceeding to extensive biostatistical analysis. Thus, it appears that miR
      155-5p is significantly overexpressed in PBMCs of CLL patients and can
      distinguish them from nonleukemic population. Kaplan-Meier OS analysis and
      bootstrap univariate Cox regression showed that high miR-155-5p expression
      predicts inferior OS for CLL patients (p < 0.001). Interestingly, miR-155-5p
      overexpression retains its unfavorable prognostic role in CLL patients stratified
      according to established prognostic factors [CD38 expression and mutational
      status of the immunoglobulin heavy chain variable region (IGHV)]. Thus, miR-155
      5p appears as a promising, independent molecular biomarker of unfavorable
      prognosis in CLL.

PMID- 29463949
TI  - Diagnostic Value of the lncRNA NEAT1 in Peripheral Blood Mononuclear Cells of
      Patients with Sepsis.
AB  - Background: This study aims to evaluate the diagnostic value of nuclear-enriched
      abundant transcript 1 (NEAT1) expression in peripheral blood mononuclear cells
      (PBMCs) for the early diagnosis of sepsis. Methods: A total of 59 patients with
      sepsis, 52 noninfectious SIRS patients, and 56 healthy controls were recruited
      fort this study. The levels of NEAT1 expression in PBMCs were measured using
      quantitative real-time polymerase chain reaction (qRT-PCR). Results: Compared
      with healthy controls, NEAT1 expression of PBMCs in sepsis and SIRS groups were
      significantly increased (3.76 +/- 0.71- and 1.64 +/- 0.43-fold, resp.) (P <
      0.01), but NEAT1 levels are significantly lower in the SIRS group than in the
      sepsis group, and there was no statistical significant relevance between
      survivors and nonsurvivors in patients with sepsis. NEAT1 with an area under the
      curve (AUC) of 0.851 (95% CI: 0.812-0.935) indicated sensitivity (67.85%) and
      specificity (87.27%) for the diagnosis for sepsis, the positive predictive value
      (PPV) was 83.3%, and the negative predictive value (NPV) was 71.6%. The AUC for
      NEAT1 in the diagnosis of SIRS versus healthy controls was 0.755 (95% CI: 0.664
      0.847), with 69.23% sensitivity and 70.91% specificity, the PPV was 72.3%, and
      the NPV was 72.49%. Conclusion: Measurement of NEAT1 expression in PBMCs could be
      considered as a good additive marker for the diagnosis of sepsis.

PMID- 29463950
TI  - Efficacy of a Computer-Assisted Cognitive Rehabilitation Intervention in
      Relapsing-Remitting Multiple Sclerosis Patients: A Multicenter Randomized
      Controlled Trial.
AB  - Cognitive impairment is frequently encountered in multiple sclerosis (MS)
      affecting between 40-65% of individuals, irrespective of disease duration and
      severity of physical disability. In the present multicenter randomized controlled
      trial, fifty-eight clinically stable RRMS patients with mild to moderate
      cognitive impairment and relatively low disability status were randomized to
      receive either computer-assisted (RehaCom) functional cognitive training with an
      emphasis on episodic memory, information processing speed/attention, and
      executive functions for 10 weeks (IG; n = 32) or standard clinical care (CG; n =
      26). Outcome measures included a flexible comprehensive neuropsychological
      battery of tests sensitive to MS patient deficits and feedback regarding personal
      benefit gained from the intervention on four verbal questions. Only the IG group
      showed significant improvements in verbal and visuospatial episodic memory,
      processing speed/attention, and executive functioning from pre - to
      postassessment. Moreover, the improvement obtained on attention was retained over
      6 months providing evidence on the long-term benefits of this intervention. Group
      by time interactions revealed significant improvements in composite cognitive
      domain scores in the IG relative to the demographically and clinically matched CG
      for verbal episodic memory, processing speed, verbal fluency, and attention.
      Treated patients rated the intervention positively and were more confident about
      their cognitive abilities following treatment.

PMID- 29463951
TI  - Targeted Delivery of the HLA-B*27-Binding Peptide into the Endoplasmic Reticulum
      Suppresses the IL-23/IL-17 Axis of Immune Cells in Spondylarthritis.
AB  - Ankylosing spondylitis (AS) is highly associated with the expression of human
      leukocyte antigen-B27 (HLA-B*27). HLA-B*27 heavy chain (B27-HC) has an intrinsic
      propensity to fold slowly, leading to the accumulation of the misfolded B27-HC in
      the endoplasmic reticulum (ER) and formation of the HLA-B*27 HC homodimer, (B27
      HC)2, by a disulfide linkage at Cys-67. (B27-HC)2 displayed on the cell surface
      can act as a ligand of the killer-cell Ig-like receptor (KIR3DL2). (B27-HC)2
      binds to KIR3DL2 of NK and Th17 cells and activates both cells, resulting in the
      activation of the IL-23/IL-17 axis to launch the inflammatory reaction in AS
      patients. However, activation of the IL-23/IL-17 axis originally derived from the
      HLA-B*27 misfolding in the ER needs to be characterized. In this study, we
      delivered two HLA-B*27-binding peptides, KRGILTLKY and SRYWAIRTR, into the ER by
      using a tat-derived peptide (GRKKRRQRRR)-His6-ubiquitin (THU) vehicle. Both
      peptides are derived from the human actin and nucleoprotein of influenza virus,
      respectively. Our results demonstrated that targeted delivery of both HLA-B*27
      binding peptides into the ER can promote the HLA-B*27 folding, decrease the
      levels of (B27-HC)2, and suppress the activation of the IL-23/IL-17 axis in
      response to lipopolysaccharide. Our findings can provide a new therapeutic
      strategy in AS.

PMID- 29463952
TI  - Phenotypic and Functional Properties of Tumor-Infiltrating Regulatory T Cells.
AB  - Regulatory T (Treg) cells maintain immune homeostasis by suppressing excessive
      immune responses. Treg cells induce tolerance against self- and foreign antigens,
      thus preventing autoimmunity, allergy, graft rejection, and fetus rejection
      during pregnancy. However, Treg cells also infiltrate into tumors and inhibit
      antitumor immune responses, thus inhibiting anticancer therapy. Depleting whole
      Treg cell populations in the body to enhance anticancer treatments will produce
      deleterious autoimmune diseases. Therefore, understanding the precise nature of
      tumor-infiltrating Treg cells is essential for effectively targeting Treg cells
      in tumors. This review summarizes recent results relating to Treg cells in the
      tumor microenvironment, with particular emphasis on their accumulation,
      phenotypic, and functional properties, and targeting to enhance the efficacy of
      anticancer treatment.

PMID- 29463953
TI  - Autosomal dominant retinitis pigmentosa rhodopsin mutant Q344X drives specific
      alterations in chromatin complex gene transcription.
AB  - Purpose: Epigenetic and transcriptional mechanisms have been shown to contribute
      to long-lasting functional changes in adult neurons. The purpose of this study
      was to identify any such modifications in diseased retinal tissues from a mouse
      model of rhodopsin mutation-associated autosomal dominant retinitis pigmentosa
      (ADRP), Q344X, relative to age-matched wild-type (WT) controls. Methods: We
      performed RNA sequencing (RNA-seq) at poly(A) selected RNA to profile the
      transcriptional patterns in 3-week-old ADRP mouse model rhodopsin Q344X compared
      to WT controls. Differentially expressed genes were determined by DESeq2 using
      the Benjamini & Hochberg p value adjustment and an absolute log2 fold change
      cutoff. Quantitative western blots were conducted to evaluate protein expression
      levels of histone H3 phosphorylated at serine 10 and histone H4. qRT-PCR was
      performed to validate the expression patterns of differentially expressed genes.
      Results: We observed significant differential expression in 2151 genes in the
      retina of Q344X mice compared to WT controls, including downregulation in the
      potassium channel gene, Kcnv2, and differential expression of histone genes,
      including the H1 family histone member, H1foo; the H3 histone family 3B, H3f3b;
      and the histone deacetylase 9, Hdac9. Quantitative western blots revealed
      statistically significant decreased protein expression of both histone H3
      phosphorylated at serine 10 and histone H4 in 3-week-old Q344X retinas.
      Furthermore, qRT-PCR performed on select differentially expressed genes based on
      our RNA-seq results revealed matched expression patterns of up or downregulation.
      Conclusions: These findings provide evidence that transcriptomic alterations
      occur in the ADRP mouse model rhodopsin Q344X retina and that these processes may
      contribute to the dysfunction and neurodegeneration seen in this animal model.

PMID- 29463954
TI  - Association of plasma osteopontin with diabetic retinopathy in Asians with type 2
      diabetes.
AB  - Purpose: Osteopontin (OPN) is a proinflammatory cytokine with diverse functions.
      Increased levels of OPN in vitreous fluid have been reported in patients with
      diabetic retinopathy (DR); however, studies on circulating OPN levels in DR are
      limited. We aim to examine the association of plasma OPN levels with the presence
      and severity of DR in a multiethnic cohort with type 2 diabetes mellitus (type 2
      diabetes) in Singapore. Methods: Plasma levels of OPN were measured using enzyme
      linked immunosorbent assay. Digital color fundus photographs were assessed for
      DR. DR severity was categorized into non-proliferative DR (NPDR) and
      proliferative DR (PDR). Gradable fundus photographs and OPN measurements for 443
      patients were used for analysis. A logistic regression model was used to evaluate
      the association of OPN with DR. Results: DR was diagnosed in 174 (39.3%)
      patients, including 132 (75.9%) with NPDR and 42 (24.1%) with PDR. The median of
      OPN was higher in the patients with DR (64.7 [49.7-89.5] ng/ml) than in the
      patients without DR (51.7 [38.9-66.9] ng/ml; p<0.001). After adjustment for
      clinical and biochemical factors, a 1-unit increase in nature logarithm (ln)
      transformed OPN was associated with the presence of DR (2.770 [1.599-3.800],
      p<0.001). The area under the curve (AUC) increased statistically significantly
      after the addition of OPN (0.805[0.763-0.846] versus 0.825 [0.785-0.865],
      p=0.011). In the severity analyses, the median of OPN was statistically
      significantly higher in the patients with PDR (76.8 [55.0-103.6] ng/ml) than in
      the patients with NPDR (61.7 [47.7-87.3] ng/ml; p=0.017). After adjustment, the 1
      unit increase in lnOPN remained associated with NPDR (2.673 [1.519-4.704],
      p=0.001) and PDR (3.389 [1.254-9.226], p=0.017), respectively (p-trend=0.001).
      Conclusions: Plasma OPN levels were associated with the presence and severity of
      DR in patients with type 2 diabetes, suggesting OPN may be useful as a potential
      biomarker for DR.

PMID- 29463956
TI  - Low-Dimensional Motor Control Representations in Throwing Motions.
AB  - In this study, we identified a low-dimensional representation of control
      mechanisms in throwing motions from a variety of subjects and target distances.
      The control representation was identified at the kinematic level in task and
      joint spaces, respectively, and at the muscle activation level using the theory
      of muscle synergies. Representative features of throwing motions in all of these
      spaces were chosen to be investigated. Features were extracted using
      factorization and clustering techniques from the muscle data of unexperienced
      subjects (with different morphologies and physical conditions) during a series of
      throwing tasks. Two synergy extraction methods were tested to assess their
      consistency. For the task features, the degrees of freedom (DoF), and the muscles
      under study, the results can be summarized as (1) a control representation across
      subjects consisting of only two synergies at the activation level and of
      representative features in the task and joint spaces, (2) a reduction of control
      redundancy (since the number of synergies are less than the number of actions to
      be controlled), (3) links between the synergies triggering intensity and the
      throwing distance, and finally (4) consistency of the extraction methods. Such
      results are useful to better represent mechanisms hidden behind such dynamical
      motions and could offer a promising control representation for synthesizing
      motions with muscle-driven characters.

PMID- 29463955
TI  - Optic nerve regeneration in the mouse is a complex trait modulated by genetic
      background.
AB  - Purpose: The present study is designed to identify the influences of genetic
      background on optic nerve regeneration using the two parental strains (C57BL/6J
      and DBA/2J) and seven BXD recombinant inbred mouse strains. Methods: To study
      regeneration in the optic nerve, Pten was knocked down in the retinal ganglion
      cells using adenoassociated virus (AAV) delivery of shRNA, and a mild
      inflammatory response was induced with an intravitreal injection of zymosan with
      CPT-cAMP. The axons of the retinal ganglion cells were damaged by optic nerve
      crush (ONC). Following a 12-day survival period, regenerating axons were labeled
      by cholera toxin B, and 2 days later, the regenerating axons within the optic
      nerve were examined. The number of axons at 0.5 mm and 1 mm from the crush site
      were counted. In addition, we measured the distance that five axons had grown
      down the nerve and the longest distance a single axon reached. Results: The
      analysis revealed a considerable amount of differential axonal regeneration
      across the seven BXD strains and the parental strains. There was a statistically
      significant difference (p=0.014 Mann-Whitney U test) in the regenerative capacity
      in the number of axons reaching 0.5 mm from a low of 236.1+/-24.4 axons in the
      BXD102 mice to a high of 759.8+/-79.2 axons in the BXD29 mice. There were also
      statistically significant differences (p=0.014 Mann-Whitney U test) in the
      distance axons traveled. Looking at a minimum of five axons, the shortest
      distance was 787.2+/-46.5 um in the BXD102 mice, and the maximum distance was
      2025.5+/-223.3 um in the BXD29 mice. Conclusions: Differences in genetic
      background can have a profound effect on axonal regeneration causing a threefold
      increase in the number of regenerating axons at 0.5 mm from the crush site and a
      2.5-fold increase in the distance traveled by at least five axons in the damaged
      optic nerve.

PMID- 29463957
TI  - Adenomas - Genetic factors in colorectal cancer prevention.
AB  - Colorectal cancer is the second most common type of cancer both in Europe and
      Poland. During the last 30 years more than a 3-fold increase has been observed in
      Poland due to environmental and genetic factors. Almost all colorectal
      malignancies are related to the formation and malignant transformation of
      colorectal dysplasia and adenoma. Efforts aiming to decrease the number of
      colorectal cancer deaths are focused on the disease early detection. Genetic
      diagnosis for hereditary syndromes predisposing to colorectal cancer has been
      developed and is a part of the routine treatment. Most cancers are sporadic. They
      often develop from polyps in the colon. In addition to the genetic events
      described in the 1990s, showing the adenoma transformation into carcinoma that
      has been a prime example of malignant transformation for a long time, there are
      also other possibilities of neoplastic transformation. The recognition of
      colorectal cancer risk factors make sense as their nature is lifestyle- and diet
      related. In this review paper those risk factors are presented and the prevention
      of colorectal cancer is discussed taking into account genetic factors.

PMID- 29463958
TI  - Interfractional diaphragm changes during breath-holding in stereotactic body
      radiotherapy for liver cancer.
AB  - Aim and background: IGRT based on bone matching may produce a large target
      positioning error in terms of the reproducibility of expiration breath-holding on
      SBRT for liver cancer. We evaluated the intrafractional and interfractional
      errors using the diaphragm position at the end of expiration by utilising Abches
      and analysed the factor of the interfractional error. Materials and methods:
      Intrafractional and interfractional errors were measured using a couple of
      frontal kV images, planning computed tomography (pCT) and daily cone-beam
      computed tomography (CBCT). Moreover, max-min diaphragm position within daily
      CBCT image sets with respect to pCT and the maximum value of diaphragm position
      difference between CBCT and pCT were calculated. Results: The mean +/- SD
      (standard deviation) of the intra-fraction diaphragm position variation in the
      frontal kV images was 1.0 +/- 0.7 mm in the C-C direction. The inter-fractional
      diaphragm changes were 0.4 +/- 4.6 mm in the C-C direction, 1.4 +/- 2.2 mm in the
      A-P direction, and -0.6 +/- 1.8 mm in the L-R direction. There were no
      significant differences between the maximum value of the max-min diaphragm
      position within daily CBCT image sets with respect to pCT and the maximum value
      of diaphragm position difference between CBCT and pCT. Conclusions: Residual
      intrafractional variability of diaphragm position is minimal, but large
      interfractional diaphragm changes were observed. There was a small effect in the
      patient condition difference between pCT and CBCT. The impact of the difference
      in daily breath-holds on the interfractional diaphragm position was large or the
      difference in daily breath-holding heavily influenced the interfractional
      diaphragm change.

PMID- 29463959
TI  - Article Watch: April 2018.
AB  - This column highlights recently published articles that are of interest to the
      readership of this publication. We encourage ABRF members to forward information
      on articles they feel are important and useful to Clive Slaughter, MCG-UGA
      Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Tel: (706) 713
      2216; Fax: (706) 713-2221; E-mail: cslaught@uga.edu, or to any member of the
      editorial board. Article summaries reflect the reviewer's opinions and not
      necessarily those of the association.

PMID- 29463961
TI  - Comparison of Chiropractic Treatment Outcomes Depending on the Language Region in
      Switzerland: A Prospective Outcomes Study.
AB  - Objectives: Switzerland has optimal conditions for research of language-based
      cultural influences on low back pain (LBP). The aim of this study was to compare
      LBP treatment outcomes after chiropractic care between patients from the German-
      and French-speaking regions of Switzerland. Methods: Baseline Numeric Rating
      Scale for pain (NRS), demographic, and Oswestry Disability Index (ODI) data were
      collected from patients presenting to 51 Swiss-German and 12 Swiss-French
      chiropractors. Prospective outcome data included the proportion reporting
      clinically relevant improvement on the Patient Global Impression of Change scale
      and the NRS change scores collected at 1 week; 1, 3, and 6 months; and 1 year.
      ODI change scores were collected until 3 months. The proportion improved between
      the 2 groups was compared using the chi2 test. NRS and ODI change scores were
      compared using the unpaired t test. Results: At baseline, only patient age
      comparing 853 Swiss-German and 215 Swiss-French patients revealed a significant
      difference. The Patient Global Impression of Change, NRS, and ODI had no
      significant differences between both patient groups up to 6 months. Between 6
      months and 1 year the proportion reporting improvement continued to increase to
      83.5% for German-speaking Swiss but reduced to 73.1% for French-speaking Swiss (P
      = .01). The NRS change scores were also higher for German speaking Swiss at 1
      year compared with Swiss-French citizens (P = .01). Conclusion: Treatment outcome
      data for LBP are comparable in the German and French parts of Switzerland until
      the 1-year time point, when people located in the French-speaking regions are
      more likely to have an increase in pain levels.

PMID- 29463960
TI  - Comparison of 68Ga-DOTA-Siglec-9 and 18F-Fluorodeoxyribose-Siglec-9: Inflammation
      Imaging and Radiation Dosimetry.
AB  - Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a ligand of
      inflammation-inducible vascular adhesion protein-1 (VAP-1). We compared 68Ga-DOTA
      and 18F-fluorodeoxyribose- (FDR-) labeled Siglec-9 motif peptides for PET
      imaging of inflammation. Methods. Firstly, we examined 68Ga-DOTA-Siglec-9 and 18F
      FDR-Siglec-9 in rats with skin/muscle inflammation. We then studied 18F-FDR
      Siglec-9 for the detection of inflamed atherosclerotic plaques in mice and
      compared it with previous 68Ga-DOTA-Siglec-9 results. Lastly, we estimated human
      radiation dosimetry from the rat data. Results. In rats, 68Ga-DOTA-Siglec-9 (SUV,
      0.88 +/- 0.087) and 18F-FDR-Siglec-9 (SUV, 0.77 +/- 0.22) showed comparable (P =
      0.29) imaging of inflammation. In atherosclerotic mice, 18F-FDR-Siglec-9 detected
      inflamed plaques with a target-to-background ratio (1.6 +/- 0.078) similar to
      previously tested 68Ga-DOTA-Siglec-9 (P = 0.35). Human effective dose estimates
      for 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9 were 0.024 and 0.022 mSv/MBq,
      respectively. Conclusion. Both tracers are suitable for PET imaging of
      inflammation. The easier production and lower cost of 68Ga-DOTA-Siglec-9 present
      advantages over 18F-FDR-Siglec-9, indicating it as a primary choice for clinical
      studies.

PMID- 29463962
TI  - A Survey of the Public Perception of Chiropractic After Exposure to Chiropractic
      Public Place Marketing Events in New Zealand.
AB  - Objective: The purpose of this study was to assess public perception of
      chiropractic public place marketing events. Method: A chiropractic public place
      marketing program was held at 3 events (a community sports event, an exposition,
      and a university campus market day) over a 5-month period in Auckland, New
      Zealand, between 2008 and 2009. Participants were interviewed by chiropractic
      students. Interview questions were standardized and sought to find out
      participants' perception of chiropractic and whether it was influenced in a
      positive or negative manner after their exposure to the marketing program.
      Results: Three hundred forty-five interviews were completed during 3 events. The
      minority of participants (15.9%) had a negative view of chiropractic, 29.2% were
      neutral, and 54.9% had a positive view of chiropractic. Of the responses of those
      surveyed, 54% did not change their opinion of chiropractic, 44.3% were more
      positive, and 1.7% were more negative. Conclusions: This study found that direct
      or indirect exposure to chiropractic public place marketing events may possibly
      influence the public perception of chiropractic. Because of the limited sample,
      these findings cannot be extrapolated to other regions or populations. Further
      studies are needed to test these findings in other world regions and in more
      controlled environments.

PMID- 29463963
TI  - Joint Manipulation: Toward a General Theory of High-Velocity, Low-Amplitude
      Thrust Techniques.
AB  - Objective: The objective of this study was to describe the initial stage of a
      generalized theory of high-velocity, low-amplitude thrust (HVLAT) techniques for
      joint manipulation. Methods: This study examined the movements described by
      authors from the fields of osteopathy, chiropractic, and physical therapy to
      produce joint cavitation in both the metacarpophalangeal (MCP) joint and the
      cervical spine apophysial joint. This study qualitatively compared the kinetics,
      the similarities, and the differences between MCP cavitation and cervical facet
      joint cavitation. A qualitative vector analysis of forces and movements was
      undertaken by constructing computer-generated, simplified graphical models of the
      MCP joint and a typical cervical apophysial joint and imposing the motions
      dictated by the clinical technique. Results: Comparing the path to cavitation of
      2 modes of HVLAT for the MCP joint, namely, distraction and hyperflexion, it was
      found that the hyperflexion method requires an axis of rotation, the hinge axis,
      which is also required for cervical HVLAT. These results show that there is an
      analogue of cervical HVLAT in one of the MCP joint HVLATs. Conclusions: The study
      demonstrated that in a theoretical model, the path to joint cavitation is the
      same for asymmetric separation of the joint surfaces in the cervical spine and
      the MCP joints.

PMID- 29463964
TI  - Culturally Sensitive Chiropractic Care of the Transgender Community: A Narrative
      Review of the Literature.
AB  - Objectives: Transgender individuals commonly experience barriers to quality
      health care and may suffer from unique musculoskeletal complaints. Although these
      needs are often inadequately addressed within the health care system, they could
      be attended to by the chiropractic community. This narrative review describes
      best practices for delivering culturally sensitive care to transgender patients
      within the context of chiropractic offices. Methods: A literature search
      generated peer-reviewed material on culturally competent care of the transgender
      community. Google Scholar and trans-health RSS feeds on social media were also
      searched to find relevant gray literature. Information pertinent to a
      chiropractic practice was identified and summarized. Results: Contemporary
      definitions of transgender, gender identity, and sexual orientation provide a
      framework for culturally sensitive language and clinic culture. Small changes in
      record keeping and office procedures can contribute to a more inclusive
      environment for transgender patients and improve a chiropractor's ability to
      collect important health history information. Special considerations during a
      musculoskeletal examination may be necessary to properly account for medical and
      nonmedical practices transgender patients may use to express their gender.
      Chiropractors should be aware of health care and social and advocacy resources
      for transgender individuals and recommend them to patients who may need
      additional support. Conclusions: Small yet intentional modifications within the
      health care encounter can enable chiropractors to improve the health and well
      being of transgender individuals and communities.

PMID- 29463965
TI  - A Literature Review of Electronic Health Records in Chiropractic Practice: Common
      Challenges and Solutions.
AB  - Objective: The purpose of this study was to review the literature on current
      challenges and propose solutions for the optimal utilization of the electronic
      health records (EHRs) in chiropractic practice. Methods: A search was performed
      in the PubMed, Index of Chiropractic Literature, and Current Index to Nursing and
      Allied Health Literature databases from November 2005 to February 2015. A
      combination of the following key words was used: electronic health records,
      electronic medical records, implementation, documentation, benefits, and
      challenges. Articles were categorized into common problems and solutions. These
      were filtered by application to chiropractic or educational institutions.
      Results: The search resulted in 45 papers, which included case reports of EHR
      implementation, governmental insurance reports, commentaries, controlled studies,
      narrative reviews of past experiences with conversion from paper systems, and the
      implementation of EHRs in small offices and chiropractic offices. Minimal
      literature was found that directly related to chiropractic EHRs. Improper
      utilization, incorrect use of the software, faulty implementation, workflow
      burdens, financial considerations, and insufficient training were found to
      negatively affect the quality of the record. Conclusions: Documentation errors
      are often innate in the EHR software. Improper utilization, insufficient
      training, or difficulty in integration of the EHR into the clinical office
      setting results in poor implementation of the electronic version of the clinical
      record. Solutions that may decrease documentation errors include EHR training,
      continued financial incentives, and appropriate implementation process and
      utilization of available software features.

PMID- 29463966
TI  - Thriving for 110 Years: National's Philosophy of Collaboration and Integration.
AB  - The National University of Health Sciences celebrated its 110th year in 2016.
      This article is an edited transcription of the presentation made by Dr Kenneth J.
      Dougherty, Chair of the Board of Trustees, at the National University of Health
      Sciences Homecoming reception on June 18, 2016, in Lombard, IL.

PMID- 29463967
TI  - The McAndrews Leadership Lecture: February 2016, by Dr Greg Kawchuk. Putting the
      "Act" Back in Chiropractic.
AB  - The McAndrews Leadership Lecture was developed by the American Chiropractic
      Association to honor the legacy of Jerome F. McAndrews, DC, and George P.
      McAndrews, JD, and their contributions to the chiropractic profession. This
      article is an edited and truncated version of the McAndrews Leadership Lecture
      given by Dr Greg Kawchuk on February 27, 2016, in Washington, DC, at the National
      Chiropractic Leadership Conference. This was the second McAndrews lecture in this
      annual series.

PMID- 29463968
TI  - The John A. Sweaney Lecture: Washington DC, March 2017, Given by Dr Geoff
      Outerbridge. Our Highest Level of Contribution: Doing the Right Thing, the Right
      Way, for the Right Reason.
AB  - The following is The John A. Sweaney Lecture delivered by Dr Geoff Outerbridge at
      the Biannual Meeting of the World Federation of Chiropractic in Washington, DC,
      on March 14, 2017.

PMID- 29463969
TI  - Sexual Dysfunction in Interstitial Cystitis.
AB  - Background/Aims: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a
      debilitating disease characterized with urgency, frequency, and pelvic pain
      affecting especially women. Sexual dysfunction in female patients with IC/BPS
      consists of dyspareunia, altered sexual desire and orgasm frequency and
      insufficient lubrication is reported to negatively affect the patient's quality
      of life. In the present study, we aimed to determine the association between
      IC/BPS and sexual dysfunction and improvement in sexual dysfunction related to
      given treatments. Methods: A PubMed/Medline and EMBASE search was conducted using
      keywords: "interstitial cystitis", "sexual dysfunction", and "bladder pain
      syndrome". Conclusion: Several studies have been conducted to determine the
      relation between IC/BPS and sexual dysfunction. And also limited studies focusing
      on IC/BPS specific treatments reported significant improvements in sexual
      function after either oral or intravesical treatment. However, given the used
      different questionnaires, study protocols, patient characteristics, previous
      treatments and follow-up period, it is not possible to make a head-to-head
      comparison of the treatment effects on sexual function. Further, randomized
      controlled studies are needed to confirm these results and make a comparison
      between effects of various treatment modalities on sexual functioning in IC/BPS.

PMID- 29463970
TI  - The Effect of Transdermal Testosterone Administration on Lower Urinary Tract
      Symptoms and Erectile Dysfunction: A Prospective, Randomized, Placebo-Controlled
      Trial.
AB  - Objective: This study aimed to evaluate the effects of transdermal testosterone
      administration on lower urinary tract symptoms (LUTS) and erectile dysfunction
      (ED). Materials and Method: Sixty-two male patients with Ageing Male Symptom
      Questionnaire (AMS-Q) scores over 27 and a total serum testosterone level below
      350 ng/dl (12.1 nmol/l) who presented to our urology clinic with complaints of
      LUTS and ED, were enrolled in this study. Uroflowmetry and the International
      Prostate Symptom Scale were used to evaluate the severity of LUTS. The
      International Index of Erectile Function was used to detect the severity of ED.
      In addition, the AMS-Q was used to quantify the severity of hypogonadism. We
      randomly divided patients into 2 groups. Thirty-one patients in the first group
      had transdermal testosterone administered at a daily dose of 50 mg (a sachet of 5
      g) on the skin for 3 months. In the second group, 31 patients had a placebo
      administered for 3 months. The scales were recompleted based on interviews and
      uroflowmetry was repeated during checks of the patients performed in the first
      and third months. Results: We detected a decrease in AMS-Q scores and an increase
      in maximum uroflow rate values and the International Index of Erectile Function
      scores in the first group compared with the placebo group. Although a decrease
      was detected in post-treatment International Prostate Symptom Scale scores in the
      first group, it was not regarded as statistically significant. Conclusion: This
      study revealed that testosterone replacement therapy is effective in improving
      LUTS and ED symptoms.

PMID- 29463971
TI  - Physician Perceptions of Patient Health: A Comparative Analysis between Urologist
      and Hospitalist Perceptions of Need for Inpatient Hospitalist Comanagement
      Following Radical Cystectomy.
AB  - Background/Aims: The morbidity of radical cystectomy remains high. A
      multidisciplinary approach utilizing hospitalist comanagement may improve
      outcomes. It is unclear what factors should be considered to determine which
      patients might benefit from this approach. We sought to determine if there are
      differences between the perceived need for co-management between urologists and
      hospitalists. Preoperative variables were analyzed to determine which factors
      might be associated with need for comanagement. Methods: A case-based survey was
      emailed to urologists and hospitalists at 3 academic institutions to investigate
      perceptions regarding need for inpatient medical comanagement of fictitious
      patients following cystectomy. Decisions were rated based on patient
      comorbidities, age, race, sex, cancer stage, neoadjuvant therapy, alcohol intake,
      performance status, and English literacy. A Wilcoxon rank sum test assessed each
      question for differences. A Mantel-Haenszel chi-square test was used to assess
      whether the proportion of respondents who advocated for comanagement increased as
      Charlson comorbidity score increased. Results: The most significant determinant
      of need for postoperative comanagement was patients' comorbidities. Urologists
      and hospitalists did not differ significantly in beliefs regarding need for
      comanagement. Conclusion: The most important determining factor for comanagement
      was presence of comorbidities. Further studies are needed to evaluate the impact
      of this multidisciplinary approach.

PMID- 29463972
TI  - Quality of Life Following Prostatectomy as a Function of Surgery Type and Degree
      of Nerve Sparing.
AB  - Objectives: To compare robotic-assisted laparoscopic prostatectomy with
      conventional retropubic radical prostatectomy in maintaining pre-surgery levels
      of urinary and sexual functioning and to evaluate the efficacy of nerve sparing
      in prostatectomies in protecting urinary functioning. Material and Methods:
      Patients (n = 385) receiving both surgical procedures were surveyed prior to
      surgery. Multiple measures, including the Expanded Prostate Cancer Index
      Composite, the Sexual Health Inventory for Men, and the International Prostate
      Symptom Score, assessed sexual and urinary function at an average of 12 months
      post-surgery. Results: Across multiple measures, while controlling for pre
      surgical sexual functioning, robotic-assisted surgery did not offer an advantage
      in maintaining sexual or urinary function an average of a year following the
      prostatectomy. Bilateral nerve sparing offered a strong and reliable advantage in
      the maintenance of sexual function, but not so regarding urinary function.
      Conclusion: While robotic-assisted prostatectomies may offer a number of medical
      advantages over open procedures, we found no significant effect on important
      quality of life outcomes associated with the technique.

PMID- 29463973
TI  - Urological Management of Extramural Malignant Ureteric Obstruction: A Survey of
      Irish Urologists.
AB  - Introduction: The absence of guidelines in the management of extramural malignant
      ureteric obstruction leads to confusion in decision making and in the interaction
      between urology and other clinical disciplines. In this study, we surveyed
      consultant urologists with the goal of achieving a better consensus on optimal
      management options. Methods: A multiple choice survey was sent via the online
      survey tool "SurveyMonkey" to all consultant urologists practicing in the
      Republic of Ireland. Results: There was a response rate of 57.5% (n = 23). Twenty
      two (96%) consultants consider the use of percutaneous nephrostomy with placement
      of antegrade ureteric stent but only 22% (n = 5) would consider using a metallic
      stent. Eleven (48%) respondents favor retrograde stenting in the first instance
      with an equal proportion choosing an antegrade method. Nine (39%) consultants
      perform the initial stent change at 4-6 months, 8 (35%) at 2-4 months, and 1 at <
      2 months and 6-10 months respectively. Total 59% (n = 13) of respondents felt
      that the duration of expected patient survival influenced their decision and
      agreement to stent with 42% (n = 8) saying this survival would need to be > 6
      months and 82% (n = 18) were generally happy with the level of ongoing
      communication between urology and the primary service managing the patient.
      Conclusion: There is a lack of consensus regarding the management of this
      challenging problem, particularly with regard to timing of first stent change and
      whether to initially use an antegrade or retrograde approach. This reflects the
      heterogeneous patient cohort and the important factors of life expectancy and
      patient co-morbidities.

PMID- 29463974
TI  - "Researching the Research" in Prostate Cancer: A Comparative Bibliometric
      Analysis of the Top 100 Cited Articles in the Field of Prostate Cancer.
AB  - Background: To perform the first comparative bibliometric analysis of the "Top
      100 (T100) cited articles in prostate cancer (PCa)". Materials and Methods: A
      comprehensive search using the Web of Science Database (v 5.21) covering the Web
      of ScienceTM Core Collection, BIOSIS Previews, Central Contents Connect, KCI
      Korean Journal Database, MEDLINE, SciELO Index (February 2016) was performed, for
      all articles relevant to PCa. Results: The T100 were cited 582 to 3,387 times,
      and were published from 1966 to 2012. The top 3 subcategories associated with PCa
      included: genetics/biomarkers (n = 34), management (n = 25), and physiology (n =
      11). T100 contributions from USA (n = 86), were most prominent. If the regional
      citation was corrected for percentage on research (citation record/percentage
      gross domestic product on research) a variation in the ranking was noted.
      Conclusion: The first bibliometric analysis in the field of PCa is presented.
      Regions that predominate the T100, include the United States and Europe. Articles
      published in higher impact factor journals, in English medium and content related
      to PCa research associated with genetics/bio-markers have the highest citation
      potential.

PMID- 29463975
TI  - Retropubic, Laparoscopic, and Robot-Assisted Radical Prostatectomy: A Comparative
      Analysis of the Surgical Outcomes in a Single Regional Center.
AB  - Background: To compare the surgical outcomes of radical prostatectomy (RP)
      performed via 3 different approaches: retropubic (RRP), laparoscopic-assisted
      (LRP), and robot-assisted (RARP), in a single non-academic regional center by a
      single surgeon. Materials and Methods: The data of patients undergoing RP from
      2005 to 2014 were reviewed. The standard approach changed through the years: RRP
      (n = 380, years 2005 to 2008), LRP (n = 240, years 2009 to 2011), and RARP (n =
      262, years 2012 to 2014). Our analysis included the last consecutive 100 RP for
      each surgical technique by a single surgeon. A logistic regression model adjusted
      for pre-and postoperative variables was done to evaluate whether transfusion,
      conversion, and post-operative complication rates were influenced by the
      approach. Results: RARP was associated with significantly lower blood loss (400
      vs. 600 and 600 ml, respectively), transfusion (6 vs. 21 and 21%, respectively),
      and shorter hospital stay (6 vs. 7 and 8 days, respectively), compared to LRP and
      RRP, and a lower conversion rate (1 vs. 12%) compared to LRP. Multivariate
      analysis adjusted for confounders confirmed that the risk of transfusion and
      conversion was significantly lower in the RARP group compared to the LRP and RRP
      groups. The RARP group was also associated with a significantly lower risk of
      complications compared to the RRP group and with a trend in favor of the RARP
      group compared to the LRP group. The 1-year continence rate was significantly
      higher in the RARP group compared to the RRP and LRP groups (80 vs. 72 and 68%,
      respectively). Conclusion: The surgical approach affected the operative outcomes
      in a regional setting. The advantages of RARP over RRP (complications,
      transfusion, conversion, hospital stay, 1-year continence) were over LRP as well,
      with the only exception being complications.

PMID- 29463976
TI  - A Simple and Novel Method to Attain Retrograde Ureteral Access after Previous
      Cohen Cross-Trigonal Ureteral Reimplantation.
AB  - Objective: To describe a simple, novel method to achieve ureteric access in the
      Cohen crossed reimplanted ureter, which will allow retrograde working access via
      the conventional transurethral method. Materials and Methods: Under cystoscopic
      vision, suprapubic needle puncture was performed. The needle was directed (bevel
      facing) towards the desired ureteric orifice (UO). A guidewire (with a floppy
      tip) was then inserted into the suprapubic needle passing into the bladder, and
      then easily passed into the crossed-reimplanted UO. The distal end of the
      guidewire was then removed through the urethra with cystoscopic grasping forceps.
      The straightened ureter then easily facilitated ureteroscopy access, retrograde
      pyelogram studies, and JJ stent insertion in a conventional transurethral method.
      Results: The UO and ureter were aligned in a more conventional orthotopic course,
      to allow for conventional transurethral working access. Conclusion: A novel
      method to access the Cohen crossed reimplanted ureter was described. All
      previously published methods of accessing the crossed ureter were critically
      appraised.

PMID- 29463977
TI  - A Ureteral Inguinoscrotal Hernia from a Pelvic Kidney.
AB  - A 74-year-old male patient with prostate cancer under remission was admitted with
      left inguinoscrotal swelling. He underwent scrotal ultrasound demonstrating a
      giant in-guinoscrotal hernia. Contrast-enhanced computerized tomography of the
      abdomen and pelvis demonstrated a left pelvic kidney associated with severe
      hydroureteronephrosis secondary to a ureteral inguinoscrotal hernia. Upon
      exploration with left inguinal incision, a paraperitoneal ureteral in
      guinoscrotal hernia and a hypertrophic left spermatic cord were observed. The
      elongated and tortuous left ureter, being pulled down to the scrotum by the
      hernia, was released from the herniating tissues fullfilling left hemiscrotum.
      The ureter was tapered followed by ureteroureterostomy. The accompanying left
      spermatic cord was excessively elongated and curled, necessitating cordectomy.
      The hernia was repaired with prolene mesh after removal of herniating peritoneal
      tissue. This is a rare case of a paraperitoneal ureteral inguinoscrotal hernia of
      the left pelvic kidney.

PMID- 29463978
TI  - Genital Dermatillomania.
AB  - Dermatillomania is a rare disease that seldom affects the genitals. Genital
      dermatillomania has not yet been recognized as a separate entity within the
      disease. The purpose of the report is to highlight a new facet of dermatillomania
      and inform urologists that dermatillomania could be a potential reason for
      genital ulcers. This report documents 2 cases of genital dermatillomania which
      vary in severity from mild (case 1), where the patient's ulcers healed after
      extensive counseling, to extremely dire (case 2), where the patient lost his
      penis after recurring ulcers and multiple reconstructive surgeries. Clinicians
      should be aware of the characteristics of dermatillomania to ensure that
      appropriate therapy can be promptly initiated to prevent morbidity.

PMID- 29463979
TI  - Patients' and Healthcare Personnel's Experiences of Health Coaching with Online
      Self-Management in the Renewing Health Project.
AB  - Background: Telehealth applications have shown positive effects for people with
      chronic conditions and their awareness of health. Objective: To describe
      patients' and healthcare personnel's experiences of using health coaching with
      online self-management in primary health care. Method: A pragmatic randomised
      controlled trial was conducted. Patients in the intervention group measured and
      reported medical parameters such as blood pressure, blood glucose, prothrombin
      complex (PK) values, and 2-channel ECG. Data were collected through a
      questionnaire, individual interviews with patients, and focus group discussions
      with healthcare personnel. The questionnaire was analysed using statistics; texts
      from interviews and focus groups were analysed using content analysis. Findings:
      Patients were satisfied and believed that the intervention had enhanced their
      care and increased accessibility without causing concerns about privacy. Although
      being positive, patients commented the lack of support and feedback from
      healthcare personnel. Healthcare personnel regarded the intervention valuable for
      the patients' abilities to perform self-management healthcare tasks but preferred
      that patients did so without them supporting the patients. Conclusion: Patients
      expressed satisfaction and acceptance regarding the use of the application. It
      seems that healthcare personnel are convinced about the benefits for patients and
      the potential for the intervention but are not convinced about its benefits for
      healthcare organisations.

PMID- 29463980
TI  - Achieving the Recommended Endotracheal Tube Cuff Pressure: A Randomized Control
      Study Comparing Loss of Resistance Syringe to Pilot Balloon Palpation.
AB  - Background: Both under- and overinflation of endotracheal tube cuffs can result
      in significant harm to the patient. The optimal technique for establishing and
      maintaining safe cuff pressures (20-30 cmH2O) is the cuff pressure manometer, but
      this is not widely available, especially in resource-limited settings where its
      use is limited by cost of acquisition and maintenance. Therefore, anesthesia
      providers commonly rely on subjective methods to estimate safe endotracheal cuff
      pressure. This study set out to determine the efficacy of the loss of resistance
      syringe method at estimating endotracheal cuff pressures. Methods: This was a
      randomized clinical trial. We enrolled adult patients scheduled to undergo
      general anesthesia for elective surgery at Mulago Hospital, Uganda. Study
      participants were randomized to have their endotracheal cuff pressures estimated
      by either loss of resistance syringe or pilot balloon palpation. The pressures
      measured were recorded. Results: One hundred seventy-eight patients were
      analyzed. 66.3% (59/89) of patients in the loss of resistance group had cuff
      pressures in the recommended range compared with 22.5% (20/89) from the pilot
      balloon palpation method. This was statistically significant. Conclusion: The
      loss of resistance syringe method was superior to pilot balloon palpation at
      administering pressures in the recommended range. This method provides a viable
      option to cuff inflation.

PMID- 29463981
TI  - Exploring the Role of Estrogens in Lizard Spermatogenesis through the Study of
      Clomiphene and FSH Effects.
AB  - Spermatogenesis is a fascinating biological process aiming to generate haploid
      spermatozoa from diploid spermatogonia through a specific hormonal network
      between gonadotropins and steroids. Increasing evidence suggests that the primary
      female sex hormone estrogen plays an active role in this process. This research
      points out on the role of estrogen during lizard spermatogenesis by using three
      experimental approaches: (1) exposure to an analogue of nonsteroidal estrogen as
      Clomiphene citrate that acts both as estrogen agonist and antagonist; (2)
      exposure to the gonadotropin FSH; and (3) exposures to FSH followed by
      Clomiphene. Histological and immunohistochemical results demonstrate that in the
      lizard Podarcis sicula during the mating period, Clomiphene as well as FSH
      determines the breakdown of spermatogenesis and the epididymal regression,
      presumably through estrogens input as indirectly demonstrated by the appearance
      of ERalpha and vitellogenin in the liver. The ability of Clomiphene to restore
      the gonadal natural condition after FSH treatment is also demonstrated. Finally,
      data indicate that lizard testis and epididymis control their morphophysiology
      regulating the intracellular presence of ERalpha.

PMID- 29463982
TI  - Distribution of Adiponectin Receptors 1 and 2 in the Rat Olfactory Bulb and the
      Effect of Adiponectin Injection on Insulin Receptor Expression.
AB  - Background: Adiponectin (APN) is an adipocyte-derived hormone that has peripheral
      beneficial effects. Although its receptors AdipoR1 and AdipoR2 are expressed in
      the brain, their function in neurons is poorly understood. The aims of this work
      were to describe the distribution of APN receptors in the olfactory bulb (OB) as
      well as the possible effects of APN injection on the insulin receptor (InsR)
      content and Akt kinase. Method: We performed the double immunofluorescence
      technique to describe the distribution of AdipoRs and the cellular type they were
      expressing. mRNA transcript and protein content were assessed by RT-PCR and
      Western blot, respectively. APN injection was performed to analyze its possible
      effect on the insulin pathway. Results: We found that AdipoRs were localized in
      all cell layers and in both neurons and astrocytes. We observed the presence of
      mRNA transcripts and immunoblot analysis confirmed the protein on the intact OB;
      APN injection in the OB resulted in a slight decrease of the total InsR and Akt
      phosphorylation and a reduction of phopho-InsR content. Conclusions: These data
      demonstrated that AdipoRs are expressed in OB regions, and APN injection could
      act as an insulin pathway modulator in the OB and thus possibly contribute to
      olfaction physiology.

PMID- 29463983
TI  - Morphological and Genetic Diversity of Rhizobia Nodulating Cowpea (Vigna
      unguiculata L.) from Agricultural Soils of Lower Eastern Kenya.
AB  - Limited nitrogen (N) content in the soil is a major challenge to sustainable and
      high crop production in many developing countries. The nitrogen fixing symbiosis
      of legumes with rhizobia plays an important role in supplying sufficient N for
      legumes and subsequent nonleguminous crops. To identify rhizobia strains which
      are suitable for bioinoculant production, characterization of rhizobia is a
      prerequisite. The objective of this study was to assess the morphological and
      genetic diversity of rhizobia that nodulates cowpea in agricultural soils of
      lower eastern Kenya. Twenty-eight rhizobia isolates were recovered from soil
      samples collected from farmers' fields in Machakos, Makueni, and Kitui counties
      in lower eastern Kenya and characterized based on morphological characteristics.
      Thirteen representative isolates were selected and characterized using BOX
      repetitive element PCR fingerprinting. Based on the dendrogram generated from
      morphological characteristics, the test isolates were distributed into two major
      clusters at a similarity of 75%. Phylogenetic tree, based on BOX repetitive
      element PCR, grouped the isolates into two clusters at 90% similarity level. The
      clustering of the isolates did not show a relationship to the origin of soil
      samples, although the isolates were genetically diverse. This study is a
      prerequisite to the selection of suitable cowpea rhizobia to develop
      bioinoculants for sustainable crop production in Kenya.

PMID- 29463984
TI  - Accelerated Computing in Magnetic Resonance Imaging: Real-Time Imaging Using
      Nonlinear Inverse Reconstruction.
AB  - Purpose: To develop generic optimization strategies for image reconstruction
      using graphical processing units (GPUs) in magnetic resonance imaging (MRI) and
      to exemplarily report on our experience with a highly accelerated implementation
      of the nonlinear inversion (NLINV) algorithm for dynamic MRI with high frame
      rates. Methods: The NLINV algorithm is optimized and ported to run on a multi-GPU
      single-node server. The algorithm is mapped to multiple GPUs by decomposing the
      data domain along the channel dimension. Furthermore, the algorithm is decomposed
      along the temporal domain by relaxing a temporal regularization constraint,
      allowing the algorithm to work on multiple frames in parallel. Finally, an
      autotuning method is presented that is capable of combining different
      decomposition variants to achieve optimal algorithm performance in different
      imaging scenarios. Results: The algorithm is successfully ported to a multi-GPU
      system and allows online image reconstruction with high frame rates. Real-time
      reconstruction with low latency and frame rates up to 30 frames per second is
      demonstrated. Conclusion: Novel parallel decomposition methods are presented
      which are applicable to many iterative algorithms for dynamic MRI. Using these
      methods to parallelize the NLINV algorithm on multiple GPUs, it is possible to
      achieve online image reconstruction with high frame rates.

PMID- 29463985
TI  - Involvement of Machine Learning for Breast Cancer Image Classification: A Survey.
AB  - Breast cancer is one of the largest causes of women's death in the world today.
      Advance engineering of natural image classification techniques and Artificial
      Intelligence methods has largely been used for the breast-image classification
      task. The involvement of digital image classification allows the doctor and the
      physicians a second opinion, and it saves the doctors' and physicians' time.
      Despite the various publications on breast image classification, very few review
      papers are available which provide a detailed description of breast cancer image
      classification techniques, feature extraction and selection procedures,
      classification measuring parameterizations, and image classification findings. We
      have put a special emphasis on the Convolutional Neural Network (CNN) method for
      breast image classification. Along with the CNN method we have also described the
      involvement of the conventional Neural Network (NN), Logic Based classifiers such
      as the Random Forest (RF) algorithm, Support Vector Machines (SVM), Bayesian
      methods, and a few of the semisupervised and unsupervised methods which have been
      used for breast image classification.

PMID- 29463986
TI  - Multiscale High-Level Feature Fusion for Histopathological Image Classification.
AB  - Histopathological image classification is one of the most important steps for
      disease diagnosis. We proposed a method for multiclass histopathological image
      classification based on deep convolutional neural network referred to as coding
      network. It can gain better representation for the histopathological image than
      only using coding network. The main process is that training a deep convolutional
      neural network is to extract high-level feature and fuse two convolutional
      layers' high-level feature as multiscale high-level feature. In order to gain
      better performance and high efficiency, we would employ sparse autoencoder (SAE)
      and principal components analysis (PCA) to reduce the dimensionality of
      multiscale high-level feature. We evaluate the proposed method on a real
      histopathological image dataset. Our results suggest that the proposed method is
      effective and outperforms the coding network.

PMID- 29463987
TI  - LET's sponge: How the lncRNA PFL promotes cardiac fibrosis.
AB  - Compared to their protein-coding counterparts, almost nothing is known about the
      role of long noncoding RNAs (lncRNAs) in cardiac fibrosis. In the current report,
      Liang and Pan et al. characterized the pro-fibrotic lncRNA PFL in respect to
      cardiac fibrosis in mice. PFL was upregulated in the hearts of mice after
      myocardial infarction and in fibrotic cardiac fibroblasts. Moreover, PFL
      competitively sponged the cardio-protective miRNA let-7d in cardiac fibroblasts.
      Knockdown of platelet activating factor receptor (PTAFR) was shown to affect the
      pro-fibrotic collagen production mediated by PFL. PTAFR overexpression also led
      to collagen production and RNA abundance of PTAFR was also regulated by miRNA let
      7d. Therefore, the PFL/PTAFR/let-7d-dependent gene regulatory mechanism proposed
      by the authors manifests the hypothesis of competing endogenous RNAs to cardiac
      fibrosis.

PMID- 29463988
TI  - Sustained Release of Immunosuppressant by Nanoparticle-anchoring Hydrogel
      Scaffold Improved the Survival of Transplanted Stem Cells and Tissue
      Regeneration.
AB  - The outcome of scaffold-based stem cell transplantation remains unsatisfied due
      to the poor survival of transplanted cells. One of the major hurdles associated
      with the stem cell survival is the immune rejection, which can be effectively
      reduced by the use of immunosuppressant. However, ideal localized and sustained
      release of immunosuppressant is difficult to be realized, because it is arduous
      to hold the drug delivery system within scaffold for a long period of time. In
      the present study, the sustained release of immunosuppressant for the purpose of
      improving the survival of stem cells was successfully realized by a nanoparticle
      anchoring hydrogel scaffold we developed. Methods: Poly (lactic-co-glycolic acid)
      (PLGA) nanoparticles were modified with RADA16 (RNPs), a self-assembling peptide,
      and then anchored to a RADA16 hydrogel (RNPs + Gel). The immobilization of RNPs
      in hydrogel was measured in vitro and in vivo, including the Brownian motion and
      cumulative leakage of RNPs and the in vivo retention of injected RNPs with
      hydrogel. Tacrolimus, as a typical immunosuppressant, was encapsulated in RNPs (T
      RNPs) that were anchored to the hydrogel and its release behavior were studied.
      Endothelial progenitor cells (EPCs), as model stem cells, were cultured in the T
      RNPs-anchoring hydrogel to test the immune-suppressing effect. The cytotoxicity
      of the scaffold against EPCs was also measured compared with free tacrolimus
      loaded hydrogel. The therapeutic efficacy of the scaffold laden with EPCs on the
      hind limb ischemia was further evaluated in mice. Results: The Brownian motion
      and cumulative leakage of RNPs were significantly decreased compared with the un
      modified nanoparticles (NPs). The in vivo retention of injected RNPs with
      hydrogel was obviously longer than that of NPs with hydrogel. The release of
      tacrolimus from T-RNPs + Gel could be sustained for 28 days. Compared with free
      tacrolimus-loaded hydrogel, the immune responses were significantly reduced and
      the survival of EPCs was greatly improved both in vitro and in vivo. The results
      of histological evaluation, including accumulation of immune cells and deposition
      of anti-graft antibodies, further revealed significantly lessened immune
      rejection in T-RNPs-anchoring hydrogel group compared with other groups. In
      pharmacodynamics study, the scaffold laden with EPCs was applied to treat hind
      limb ischemia in mice and significantly promoted the blood perfusion (~91 %
      versus ~36 % in control group). Conclusion: The nanoparticle-anchoring hydrogel
      scaffold is promising for localized immunosuppressant release, thereby can
      enhance the survival of transplanted cells and finally lead to successful tissue
      regeneration.

PMID- 29463989
TI  - Combined delivery of sorafenib and a MEK inhibitor using CXCR4-targeted
      nanoparticles reduces hepatic fibrosis and prevents tumor development.
AB  - Liver damage and fibrosis are precursors of hepatocellular carcinoma (HCC). In
      HCC patients, sorafenib-a multikinase inhibitor drug-has been reported to exert
      anti-fibrotic activity. However, incomplete inhibition of RAF activity by
      sorafenib may also induce paradoxical activation of the mitogen-activated protein
      kinase (MAPK) pathway in malignant cells. The consequence of this effect in non
      malignant disease (hepatic fibrosis) remains unknown. This study aimed to examine
      the effects of sorafenib on activated hepatic stellate cells (HSCs), and develop
      effective therapeutic approaches to treat liver fibrosis and prevent cancer
      development. Methods: We first examined the effects of sorafenib in combination
      with MEK inhibitors on fibrosis pathogenesis in vitro and in vivo. To improve the
      bioavailability and absorption by activated HSCs, we developed CXCR4-targeted
      nanoparticles (NPs) to co-deliver sorafenib and a MEK inhibitor to mice with
      liver damage. Results: We found that sorafenib induced MAPK activation in HSCs,
      and promoted their myofibroblast differentiation. Combining sorafenib with a MEK
      inhibitor suppressed both paradoxical MAPK activation and HSC activation in
      vitro, and alleviated liver fibrosis in a CCl4-induced murine model of liver
      damage. Furthermore, treatment with sorafenib/MEK inhibitor-loaded CXCR4-targeted
      NPs significantly suppressed hepatic fibrosis progression and further prevented
      fibrosis-associated HCC development and liver metastasis. Conclusions: Our
      results show that combined delivery of sorafenib and a MEK inhibitor via CXCR4
      targeted NPs can prevent activation of ERK in activated HSCs and has anti
      fibrotic effects in the CCl4-induced murine model. Targeting HSCs represents a
      promising strategy to prevent the development and progression of fibrosis
      associated HCC.

PMID- 29463990
TI  - Mesenchymal Stromal/stem Cell-derived Extracellular Vesicles Promote Human
      Cartilage Regeneration In Vitro.
AB  - : Osteoarthritis (OA) is a rheumatic disease leading to chronic pain and
      disability with no effective treatment available. Recently, allogeneic human
      mesenchymal stromal/stem cells (MSC) entered clinical trials as a novel therapy
      for OA. Increasing evidence suggests that therapeutic efficacy of MSC depends on
      paracrine signalling. Here we investigated the role of extracellular vesicles
      (EVs) secreted by human bone marrow derived MSC (BMMSC) in human OA cartilage
      repair. METHODS: To test the effect of BMMSC-EVs on OA cartilage inflammation,
      TNF-alpha-stimulated OA chondrocyte monolayer cultures were treated with BMMSC
      EVs and pro-inflammatory gene expression was measured by qRT-PCR after 48 h. To
      assess the impact of BMMSC-EVs on cartilage regeneration, BMMSC-EVs were added to
      the regeneration cultures of human OA chondrocytes, which were analyzed after 4
      weeks for glycosaminoglycan content by 1,9-dimethylmethylene blue (DMMB) assay.
      Furthermore, paraffin sections of the regenerated tissue were stained for
      proteoglycans (safranin-O) and type II collagen (immunostaining). RESULTS: We
      show that BMMSC-EVs inhibit the adverse effects of inflammatory mediators on
      cartilage homeostasis. When co-cultured with OA chondrocytes, BMMSC-EVs abrogated
      the TNF-alpha-mediated upregulation of COX2 and pro-inflammatory interleukins and
      inhibited TNF-alpha-induced collagenase activity. BMMSC-EVs also promoted
      cartilage regeneration in vitro. Addition of BMMSC-EVs to cultures of
      chondrocytes isolated from OA patients stimulated production of proteoglycans and
      type II collagen by these cells. CONCLUSION: Our data demonstrate that BMMSC-EVs
      can be important mediators of cartilage repair and hold great promise as a novel
      therapeutic for cartilage regeneration and osteoarthritis.

PMID- 29463991
TI  - Cancer-associated Fibroblast-derived IL-6 Promotes Head and Neck Cancer
      Progression via the Osteopontin-NF-kappa B Signaling Pathway.
AB  - Osteopontin (OPN), a chemokine-like protein, plays a crucial role in the
      proliferation and metastasis of various cancers. However, how tumor stroma
      modulates the expression of neoplastic OPN and the multifaceted roles of OPN in
      head and neck cancer (HNC) are unclear. In this study, we tried to investigate
      the bridging role of OPN between tumor stroma and cancer cells. Methods:
      Immunohistochemical staining and quantitative real-time PCR were used to detect
      OPN expression in HNC tissues, and the correlations between OPN expression and
      clinicopathologic features were then analyzed. We used a co-culture assay to
      study the modulatory role of IL-6 on OPN expression and immunoprecipitation
      analysis was used to determine the endogenous interaction between OPN and
      integrin alphavbeta3. Furthermore, a xenograft assay was carried out to confirm
      the tumor-promoting role and the potential therapeutic value of OPN in HNC.
      Results: We found that OPN was significantly up-regulated in HNCs, and the
      elevated OPN was correlated with poor prognosis. Moreover, we identified IL-6
      secreted by cancer-associated fibroblasts (CAFs) as the major upstream molecule
      that triggers the induction of neoplastic OPN. As such, during the interaction of
      fibroblasts and cancer cells, the increased neoplastic OPN induced by stromal IL
      6 accelerated the growth, migration and invasion of cancer cells. More
      importantly, we also showed that soluble OPN could promote HNC progression via
      the integrin alphavbeta3-NF-kappa B pathway, and the combination of OPN and IL-6
      had a better prognostic and diagnostic performance in HNC than either molecule
      alone. Conclusion: Our study identified a novel modulatory role for OPN in HNC
      progression and further demonstrated that the combination of OPN and IL-6 might
      be a promising prognostic and diagnostic indicator as well as a potential cancer
      therapeutic target.

PMID- 29463992
TI  - Investigating the Intracellular Behaviors of Liposomal Nanohybrids via SERS:
      Insights into the Influence of Metal Nanoparticles.
AB  - The recent proposition to combine liposomes with nanoparticles presents great
      opportunities to develop multifunctional drug delivery platforms. Although
      impressive progress has been made, attempts to elucidate the role nanoparticles
      play in the integral nanohybrids are still rather limited. Here, using surface
      enhanced Raman scattering (SERS) technique, we investigate the influence of metal
      nanoparticles on the liposomal properties, ranging from drug release to
      intracellular movement. Specifically, we prepared SERS-active nanohybrids by
      attaching metal nanoparticles to liposomes and employed SERS signals to explore
      the intracellular behavior of the nanohybrids. Once deposited on the cell
      membrane, the nanohybrids entered tumor cells via clathrin-mediated endocytosis
      and then moved to lysosomes. In comparison with pure liposomes, metal
      nanoparticles in the nanohybrids had little influence on the properties of
      liposomes. This study fills the gap of the function of nanoparticles in the
      overall nanohybrids, which provides a significant prerequisite for efficient drug
      delivery in therapeutic applications.

PMID- 29463993
TI  - All-in-One Theranostic Nanoplatform Based on Hollow MoSx for Photothermally
      maneuvered Oxygen Self-enriched Photodynamic Therapy.
AB  - : Photodynamic therapy (PDT) kills cancer cells by converting tumor-dissolved
      oxygen into reactive singlet oxygen (1O2) using a photosensitizer under laser
      irradiation. However, pre-existing hypoxia in tumors and oxygen consumption
      during PDT can result in an inadequate oxygen supply, which in turn hampers PDT
      efficacy. Herein, an O2 self-sufficient nanotheranostic platform based on hollow
      MoSx nanoparticles (HMoSx) with oxygen-saturated perfluorohexane (O2@PFH) and
      surface-modified human serum albumin (HSA)/chloride aluminium phthalocyanine
      (AlPc) (O2@PFH@HMoSx-HSA/AlPc), has been designed for the imaging and oxygen self
      enriched photodynamic therapy (Oxy-PDT) of cancer. METHODS: The in vitro anti
      cancer activity and intracellular 1O2 generation performance of the nanoparticles
      were examined using 4T1 cells. We also evaluated the multimodal imaging
      capabilities and anti-tumor efficiency of the prepared nanoparticles in vivo
      using a 4T1 tumor-bearing nude mouse model. RESULTS: This nanoplatform could
      achieve the distinct in vivo fluorescence (FL)/photoacoustic (PA)/X-ray computed
      tomography (CT) triple-model imaging-guided photothermally-maneuvered Oxy-PDT.
      Interestingly, the fluorescence and Oxy-PDT properties of O2@PFH@HMoSx-HSA/AlPc
      were considerably quenched; however, photothermal activation by 670 nm laser
      irradiation induced a significant increase in temperature, which empowered the
      Oxy-PDT effect of the nanoparticles. In this study, O2@PFH@HMoSx-HSA/AlPc
      demonstrated a great potential to image and treat tumors both in vitro and in
      vivo, showing complete tumor-inhibition over 16 days after treatment in the 4T1
      tumor model. CONCLUSION: O2@PFH@HMoSx-HSA/AlPc is promising to be used as novel
      multifunctional theranostic nanoagent for triple-modal imaging as well as single
      wavelength NIR laser triggered PTT/Oxy-PDT synergistic therapy.

PMID- 29463994
TI  - The Homeotic Protein SIX3 Suppresses Carcinogenesis and Metastasis through
      Recruiting the LSD1/NuRD(MTA3) Complex.
AB  - : The homeodomain transcription factor SIX3 was recently reported to be a
      negative regulator of the Wnt pathway and has an emerging role in cancer.
      However, how SIX3 contributes to tumorigenesis and metastasis is poorly
      understood. METHODS: We employed affinity purification and mass spectrometry (MS)
      to identify the proteins physically associated with SIX3. Genome-wide analysis of
      the SIX3/LSD1/NuRD(MTA3) complex using a chromatin immunoprecipitation-on-chip
      approach identified a cohort of target genes including WNT1 and FOXC2, which are
      critically involved in cell proliferation and epithelial-to-mesenchymal
      transition. Also, we used flow cytometry, growth curve analysis, EdU
      incorporation assay, colony formation assays, trans-well invasion assays,
      immunohistochemical staining and in vivo bioluminescence assay to investigate the
      function of SIX3 in tumorigenesis. RESULTS: We demonstrate that the
      SIX3/LSD1/NuRD(MTA3) complex inhibits carcinogenesis in breast cancer cells and
      suppresses metastasis in breast cancer. SIX3 expression is downregulated in
      various human cancers and high SIX3 is correlated with improved prognosis.
      CONCLUSION: Our study revealed an important mechanistic link between the loss of
      function of SIX3 and tumor progression, identified a molecular basis for the
      opposing actions of MTA1 and MTA3, and may provide new potential prognostic
      indicators and targets for cancer therapy.

PMID- 29463995
TI  - O2-generating MnO2 nanoparticles for enhanced photodynamic therapy of bladder
      cancer by ameliorating hypoxia.
AB  - Photodynamic therapy (PDT) is an emerging effective treatment for cancer.
      However, the great promise of PDT for bladder cancer therapy has not yet been
      realized because of tumor hypoxia. To address this challenge, we fabricated O2
      generating HSA-MnO2-Ce6 NPs (HSA for human serum albumin, Ce6 for chlorin e6, and
      NPs for nanoparticles) to overcome tumor hypoxia and thus enhance the
      photodynamic effect for bladder cancer therapy. Methods: The HSA-MnO2-Ce6 NPs
      were prepared. We investigated the O2 generation of NPs in vitro and in vivo. The
      orthotopic bladder cancer model in C57BL/6 mice was established for in vivo
      study, and dual-modal imaging of NPs were demonstrated. Therapeutic efficacy of
      NPs for bladder cancer was evaluated. Results: HSA-MnO2-Ce6 NPs had an excellent
      performance in generating O2in vitro upon reaction with H2O2 at endogenous
      levels. Moreover, 1O2 generation was increased two-fold by using HSA-MnO2-Ce6 NPs
      instead of HSA-Ce6 NPs in the presence of H2O2 under 660 nm laser irradiation. In
      vitro cell viability assays showed that HSA-MnO2-Ce6 NPs themselves were non
      toxic but greatly enhanced PDT effects on bladder cancer cells under laser
      irradiation. In vivo near-infrared (NIR) fluorescence and magnetic resonance (MR)
      imaging suggested the excellent bladder tumor-targeting property of HSA-MnO2-Ce6
      NPs. O2 content in orthotopic bladder cancer was increased 3.5-fold after
      injection of HSA-MnO2-Ce6 NPs as compared with pre-injection. Given the excellent
      tumor-targeting ability and negligible toxicity, HSA-MnO2-Ce6 NPs were then used
      to treat orthotopic bladder cancer by PDT. The PDT with HSA-MnO2-Ce6 NPs showed
      remarkably improved therapeutic efficacy and significantly prolonged lifetime of
      mice as compared with controls. Conclusion: This study not only demonstrated the
      great potential of HSA-MnO2-Ce6 NPs for bladder cancer photodynamic ablation but
      also provided a new therapeutic strategy to overcoming tumor hypoxia.

PMID- 29463996
TI  - Black Phosphorus and its Biomedical Applications.
AB  - Black phosphorus (BP), also known as phosphorene, has attracted recent scientific
      attention since its first successful exfoliation in 2014 owing to its unique
      structure and properties. In particular, its exceptional attributes, such as the
      excellent optical and mechanical properties, electrical conductivity and electron
      transfer capacity, contribute to its increasing demand as an alternative to
      graphene-based materials in biomedical applications. Although the outlook of this
      material seems promising, its practical applications are still highly
      challenging. In this review article, we discuss the unique properties of BP,
      which make it a potential platform for biomedical applications compared to other
      2D materials, including graphene, molybdenum disulphide (MoS2), tungsten
      diselenide (WSe2) and hexagonal boron nitride (h-BN). We then introduce various
      synthesis methods of BP and review its latest progress in biomedical
      applications, such as biosensing, drug delivery, photoacoustic imaging and cancer
      therapies (i.e., photothermal and photodynamic therapies). Lastly, the existing
      challenges and future perspective of BP in biomedical applications are briefly
      discussed.

PMID- 29463997
TI  - Targeting ALDH2 for Therapeutic Interventions in Chronic Pain-Related Myocardial
      Ischemic Susceptibility.
AB  - Clinical observations have demonstrated a link between chronic pain and increased
      ischemic heart disease mortality, but the mechanisms remain elusive. Reactive
      aldehydes have recently been confirmed as a new player in pain pathologies, while
      our previous study demonstrated that reactive aldehydes (4-HNE) induced carbonyl
      stress contributing to myocardial ischemic intolerance. The aim of this study was
      to explore whether chronic pain increases susceptibility to myocardial
      ischemia/reperfusion (MI/R) injury and to investigate the underlying mechanisms
      focusing on toxic aldehyde and carbonyl stress. Methods: Chronic pain was induced
      by chronic compression of the dorsal root ganglion (CCD). After 2 weeks CCD,
      aldehyde dehydrogenase (ALDH2) KO or wild-type (WT) littermate mice were then
      subjected to in vivo MI/R. Results: In CCD-WT mice, heightened nociception
      paralleled circulating aldehyde (4-HNE) accumulation and cardiac protein
      carbonylation. Mechanistically, CCD-induced 4-HNE overload provoked cardiac
      Sirtuin 1 (SIRT1) carbonylative inactivation and inhibited Liver kinase B1 (LKB1)
      - AMP-activated protein kinase (LKB1-AMPK) interaction, which resulted in
      exacerbated MI/R injury and higher mortality compared with non-CCD WT mice. ALDH2
      deficiency further aggravated CCD-induced susceptibility to MI/R injury.
      Exogenous 4-HNE exposure in peripheral tissue mimicked chronic pain-induced
      aldehyde overload, elicited sustained allodynia and increased MI/R injury.
      However, cardiac-specific ALDH2 upregulation by AAV9-cTNT-mediated gene delivery
      significantly ameliorated chronic pain-induced SIRT1 carbonylative inactivation
      and decreased MI/R injury (minor infarct size, less apoptosis, and improved
      cardiac function). Conclusion: Collectively, chronic pain-enhanced carbonyl
      stress promotes myocardial ischemic intolerance by SIRT1 carbonylative
      inactivation and impairment of LKB1-AMPK interaction. ALDH2 activation and
      prevention of protein carbonylation may be a potential therapeutic target for
      myocardial ischemic vulnerability in chronic pain patients. Our results newly
      provided overlapping cellular mechanisms of chronic pain and myocardial
      dysfunction interplay.

PMID- 29463998
TI  - Octopod PtCu Nanoframe for Dual-Modal Imaging-Guided Synergistic Photothermal
      Radiotherapy.
AB  - Heavy atom nanoparticles have high X-ray absorption capacity and near infrared
      (NIR) photothermal conversion efficiency, which could be used as radio
      sensitizers. We hypothesized that concave PtCu octopod nanoframes (OPCNs) would
      be an efficient nanoplatform for synergistic radio-photothermal tumor ablation.
      Methods: In this study, we newly exploited a folic acid-receptor (FR) mediated
      photothermal radiotherapy nanoagent base on OPCNs. OPCNs were synthesized with a
      hydrothermal method and then modified with polyethylene glycol (PEG) and folic
      acid (FA). A series of physical and chemical characterizations, cytotoxicity,
      targeting potential, endocytosis mechanism, biodistribution, systematic
      toxicological evaluation, pharmacokinetics, applications of OPCNs-PEG-FA for in
      vitro and in vivo infrared thermal imaging (ITI)/photoacoustic imaging (PAI) dual
      modal imaging and synergistic photothermal radiotherapy against tumor were
      carried out. Results: The OPCNs-PEG-FA demonstrated good biocompatibility, strong
      NIR absorption and X-ray radio-sensitization, which enabling it to track and
      visualize tumor in vivo via ITI/PAI dual-modal imaging. Moreover, the as
      synthesized OPCNs-PEG-FA exhibited remarkable photothermal therapy (PTT) and
      radiotherapy (RT) synergistic tumor inhibition when treated with NIR laser and X
      ray. Conclusion: A novel multifunctional theranostic nanoplatform based on OPCNs
      was designed and developed for dual-modal image-guided synergistic tumor
      photothermal radiotherapy.

PMID- 29464000
TI  - Nondestructive Analysis of Tumor-Associated Membrane Protein Integrating Imaging
      and Amplified Detection in situ Based on Dual-Labeled DNAzyme.
AB  - Comprehensive analysis of the expression level and location of tumor-associated
      membrane proteins (TMPs) is of vital importance for the profiling of tumor cells.
      Currently, two kinds of independent techniques, i.e. ex situ detection and in
      situ imaging, are usually required for the quantification and localization of
      TMPs respectively, resulting in some inevitable problems. Methods: Herein, based
      on a well-designed and fluorophore-labeled DNAzyme, we develop an integrated and
      facile method, in which imaging and quantification of TMPs in situ are achieved
      simultaneously in a single system. The labeled DNAzyme not only produces
      localized fluorescence for the visualization of TMPs but also catalyzes the
      cleavage of a substrate to produce quantitative fluorescent signals that can be
      collected from solution for the sensitive detection of TMPs. Results: Results
      from the DNAzyme-based in situ imaging and quantification of TMPs match well with
      traditional immunofluorescence and western blotting. In addition to the advantage
      of two-in-one, the DNAzyme-based method is highly sensitivity, allowing the
      detection of TMPs in only 100 cells. Moreover, the method is nondestructive.
      Cells after analysis could retain their physiological activity and could be
      cultured for other applications. Conclusion: The integrated system provides solid
      results for both imaging and quantification of TMPs, making it a competitive
      method over some traditional techniques for the analysis of TMPs, which offers
      potential application as a toolbox in the future.

PMID- 29463999
TI  - Stimuli-Responsive Nanomedicines for Overcoming Cancer Multidrug Resistance.
AB  - Chemotherapy is still a main option for cancer therapy, but its efficacy is often
      unsatisfying due to multidrug resistance (MDR). The tumor microenvironment is
      considered a dominant factor causing MDR. Stimuli-responsive nanomedicines
      exhibit many superiorities for reversal of MDR. As smart systems, stimuli
      responsive nanomedicines are desirable for achieving site-specific accumulation
      and triggered drug release in response to slight changes in physicochemical
      properties in pathological conditions or to exogenous stimuli. In this review, we
      highlight the current progress of various nanomedicines with different stimuli
      responsive capabilities for overcoming MDR. The materials, design, construction
      as well as efficacy in overcoming MDR of these nanomedicines are discussed.
      Eventually, we look forward to forthcoming intelligent nanoparticle systems with
      new mechanisms to deliver drugs for practical applications in conquering cancer
      MDR.

PMID- 29464001
TI  - PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop regulates the biological behavior
      of glioma cells.
AB  - Rationale: PIWI-interacting RNAs (piRNAs), a class of newly discovered small RNA
      molecules that function by binding to the Argonaute protein family (i.e., the
      PIWIL protein subfamily), and long noncoding RNAs (lncRNA) are implicated in
      several cancers. However, the detailed roles of ncRNAs in glioma remain unclear.
      Methods: The expression of PIWIL3, piR-30188, OIP5-AS1, miR-367, CEBPA and TRAF4
      were measured in glioma tissues and cells. The role of PIWIL3/OIP5-AS1/miR-367
      3p/CEBPA feedback loop was evaluated in cell and animal models. The association
      of the above molecules was analyzed. Results: Over-expression of PIWIL3, piR
      30188 and miR-367-3p or knockdown of OIP5-AS1 resulted in inhibition of glioma
      cells progression. Binding sites between piR-30188 and OIP5-AS1 as well as
      between OIP5-AS1 and miR-367-3p were confirmed by RNA immunoprecipitation and
      luciferase assays. OIP5-AS1 knockdown or miR-367-3p over-expression contributed
      to a decrease in CEBPA (CCAAT/enhancer binding protein alpha) protein.
      Furthermore, CEBPA was detected as a target of miR-367-3p and played an oncogenic
      role in glioma. Treatment with CEBPA and miR-367-3p resulted in the modulation of
      downstream TRAF4 (TNF receptor-associated factor 4). PIWIL3 was also a target of
      CEBPA, forming a positive feedback loop in the growth regulation of glioma cells.
      Significantly, knockdown of OIP5-AS1 combined with over-expression of PIWIL3 and
      miR-367-3p resulted in tumor regression and extended survival in vivo.
      Conclusion: These results identified a novel molecular pathway in glioma cells
      that may provide a potential innovative approach for tumor therapy.

PMID- 29464002
TI  - MiR-205-5p and miR-342-3p cooperate in the repression of the E2F1 transcription
      factor in the context of anticancer chemotherapy resistance.
AB  - High rates of lethal outcome in tumour metastasis are associated with the
      acquisition of invasiveness and chemoresistance. Several clinical studies
      indicate that E2F1 overexpression across high-grade tumours culminates in
      unfavourable prognosis and chemoresistance in patients. Thus, fine-tuning the
      expression of E2F1 could be a promising approach for treating patients showing
      chemoresistance. Methods: We integrated bioinformatics, structural and kinetic
      modelling, and experiments to study cooperative regulation of E2F1 by microRNA
      (miRNA) pairs in the context of anticancer chemotherapy resistance. Results: We
      showed that an enhanced E2F1 repression efficiency can be achieved in
      chemoresistant tumour cells through two cooperating miRNAs. Sequence and
      structural information were used to identify potential miRNA pairs that can form
      tertiary structures with E2F1 mRNA. We then employed molecular dynamics
      simulations to show that among the identified triplexes, miR-205-5p and miR-342
      3p can form the most stable triplex with E2F1 mRNA. A mathematical model
      simulating the E2F1 regulation by the cooperative miRNAs predicted enhanced E2F1
      repression, a feature that was verified by in vitro experiments. Finally, we
      integrated this cooperative miRNA regulation into a more comprehensive network to
      account for E2F1-related chemoresistance in tumour cells. The network model
      simulations and experimental data indicate the ability of enhanced expression of
      both miR-205-5p and miR-342-3p to decrease tumour chemoresistance by
      cooperatively repressing E2F1. Conclusions: Our results suggest that pairs of
      cooperating miRNAs could be used as potential RNA therapeutics to reduce E2F1
      related chemoresistance.

PMID- 29464003
TI  - 68Ga-BBN-RGD PET/CT for GRPR and Integrin alphavbeta3 Imaging in Patients with
      Breast Cancer.
AB  - Purpose: This study was to assess a gastrin-releasing peptide receptor (GRPR) and
      integrin alphavbeta3 dual targeting tracer 68Ga-BBN-RGD for positron emission
      tomography (PET)/computed tomography (CT) imaging of breast cancer and
      metastasis. Materials and Methods: Twenty-two female patients were recruited
      either with suspected breast cancer on screening mammography (n = 16) or
      underwent breast cancer radical mastectomy (n = 6). All the 22 patients underwent
      PET/CT at 30-45 min after intravenous injection of 68Ga-BBN-RGD. Eleven out of 22
      patients also accepted 68Ga-BBN PET/CT within 2 weeks for comparison. A final
      diagnosis was made based on the histopathologic examination of surgical excision
      or biopsy. Results: Both the primary cancer and metastases showed positive 68Ga
      BBN-RGD accumulation. The T/B ratios of 68Ga-BBN-RGD accumulation were 2.10 to
      9.44 in primary cancer and 1.10 to 3.71 in axillary lymph node metastasis, 3.80
      to 10.7 in distant lymph nodes, 2.70 to 5.35 in lung metastasis and 3.17 to 22.8
      in bone metastasis, respectively. For primary lesions, the SUVmax from 68Ga-BBN
      RGD PET in ER positive group was higher than that in ER negative group (P <
      0.01). For both primary and metastatic lesions, SUVmean quantified from 68Ga-BBN
      RGD PET correlated well with both GRPR expression and integrin alphavbeta3
      expression. Conclusion: This study demonstrated significant uptake of a new type
      of dual integrin alphavbeta3 and GRPR targeting radiotracer in both the primary
      lesion and the metastases of breast cancer. 68Ga-BBN-RGD PET/CT may be of great
      value in discerning both primary breast cancers, axillary lymph node metastasis
      and distant metastases.

PMID- 29464005
TI  - Non-invasive monitoring of in vivo hydrogel degradation and cartilage
      regeneration by multiparametric MR imaging.
AB  - Numerous biodegradable hydrogels for cartilage regeneration have been widely used
      in the field of tissue engineering. However, to non-invasively monitor hydrogel
      degradation and efficiently evaluate cartilage restoration in situ is still
      challenging. Methods: A ultrasmall superparamagnetic iron oxide (USPIO)-labeled
      cellulose nanocrystal (CNC)/silk fibroin (SF)-blended hydrogel system was
      developed to monitor hydrogel degradation during cartilage regeneration. The
      physicochemical characterization and biocompatibility of the hydrogel were
      evaluated in vitro. The in vivo hydrogel degradation and cartilage regeneration
      of different implants were assessed using multiparametric magnetic resonance
      imaging (MRI) and further confirmed by histological analysis in a rabbit
      cartilage defect model for 3 months. Results: USPIO-labeled hydrogels showed
      sufficient MR contrast enhancement and retained stability without loss of the
      relaxation rate. Neither the mechanical properties of the hydrogels nor the
      proliferation of bone-marrow mesenchymal stem cells (BMSCs) were affected by
      USPIO labeling in vitro. CNC/SF hydrogels with BMSCs degraded more quickly than
      the acellular hydrogels as reflected by the MR relaxation rate trends in vivo.
      The morphology of neocartilage was noninvasively visualized by the three
      dimensional water-selective cartilage MRI scan sequence, and the cartilage repair
      was further demonstrated by macroscopic and histological observations.
      Conclusion: This USPIO-labeled CNC/SF hydrogel system provides a new perspective
      on image-guided tissue engineering for cartilage regeneration.

PMID- 29464004
TI  - Biomimetic nanoparticles with enhanced affinity towards activated endothelium as
      versatile tools for theranostic drug delivery.
AB  - Activation of the vascular endothelium is characterized by increased expression
      of vascular adhesion molecules and chemokines. This activation occurs early in
      the progression of several diseases and triggers the recruitment of leukocytes.
      Inspired by the tropism of leukocytes, we investigated leukocyte-based biomimetic
      nanoparticles (i.e., leukosomes) as a novel theranostic platform for inflammatory
      diseases. Methods: Leukosomes were assembled by combining phospholipids and
      membrane proteins from leukocytes. For imaging applications, phospholipids
      modified with rhodamine and gadolinium were used. Leukosomes incubated with
      antibodies blocking lymphocyte function-associated antigen 1 (LFA-1) and CD45
      were administered to explore their roles in targeting inflammation. In addition,
      relaxometric assessment of NPs was evaluated. Results: Liposomes and leukosomes
      were both spherical in shape with sizes ranging from 140-170 nm. Both NPs
      successfully integrated 8 and 13 ug of rhodamine and gadolinium, respectively,
      and demonstrated less than 4% variation in physicochemical features. Leukosomes
      demonstrated a 16-fold increase in breast tumor accumulation relative to
      liposomes. Furthermore, quantification of leukosomes in tumor vessels
      demonstrated a 4.5-fold increase in vessel lumens and a 14-fold increase in
      vessel walls. Investigating the targeting mechanism of action revealed that
      blockage of LFA-1 on leukosomes resulted in a 95% decrease in tumor accumulation.
      Whereas blockage of CD45 yielded a 60% decrease in targeting and significant
      increases in liver and spleen accumulation. In addition, when administered in
      mice with atherosclerotic plaques, leukosomes exhibited a 4-fold increase in the
      targeting of inflammatory vascular lesions. Lastly, relaxometric assessment of
      NPs demonstrated that the incorporation of membrane proteins into leukosomes did
      not impact the r1 and r2 relaxivities of the NPs, demonstrating 6 and 30 mM-1s-1,
      respectively. Conclusion: Our study demonstrates the ability of leukosomes to
      target activated vasculature and exhibit superior accumulation in tumors and
      vascular lesions. The versatility of the phospholipid backbone within leukosomes
      permits the incorporation of various contrast agents. Furthermore, leukosomes can
      potentially be loaded with therapeutics possessing diverse physical properties
      and thus warrant further investigation toward the development of powerful
      theranostic agents.

PMID- 29464006
TI  - Delivery of Sonic Hedgehog Gene Repressed Irradiation-induced Cellular Senescence
      in Salivary Glands by Promoting DNA Repair and Reducing Oxidative Stress.
AB  - Rationale: Irreversible hypofunction of salivary glands or xerostomia is common
      in head and neck cancer survivors treated with radiotherapy even when various new
      techniques are applied to minimize the irradiation (IR) damage. This condition
      severely impairs the quality of life of patients and can only be temporarily
      relieved with current treatments. We found recently that transient expression of
      Sonic Hedgehog (Shh) in salivary glands after IR rescued salivary function, but
      the underlying mechanisms are not totally clear. Methods: We generated a mouse
      model of IR-induced hyposalivation, and delivered adenoviral vectors carrying Shh
      or control GFP gene into submandibular glands (SMGs) via retrograde ductal
      instillation 3 days after IR. The cellular senescence was evaluated by senescence
      associated beta-galactosidase assay and the expression of senescence markers. The
      underlying mechanisms were explored by examining DNA damage, oxidative stress,
      and the expression of related genes by qRT-PCR, Western blot and
      immunofluorescent staining. Results: Shh gene transfer repressed IR-induced
      cellular senescence by promoting DNA repair and decreasing oxidative stress,
      which is mediated through upregulating expression of genes related to DNA repair
      such as survivin and miR-21 and repressing expression of pro-senescence gene
      Gdf15 likely downstream of miR-21. Conclusion: Repressing cellular senescence
      contributes to the rescue of IR-induced hyposalivation by transient activation of
      Hh signaling, which is related to enhanced DNA repair and decreased oxidative
      stress in SMGs.

PMID- 29464007
TI  - Diagnosis of LVAD Thrombus using a High-Avidity Fibrin-Specific 99mTc Probe.
AB  - Treatment of advanced heart failure with implantable LVADs is increasing, driven
      by profound unmet patient need despite potential serious complications: bleeding,
      infection, and thrombus. The experimental objective was to develop a sensitive
      imaging approach to assess early thrombus accumulation in LVADs under operational
      high flow and high shear rates. Methods: A monomeric bifunctional ligand with a
      fibrin-specific peptide, a short spacer, and 99mTc chelating amino acid sequence
      (F1A) was developed and compared to its tetrameric PEG analogue (F4A).
      Results:99mTc attenuation by LVAD titanium (1 mm) was 23%. 99mTc-F1A affinity to
      fibrin was Kd ~10 uM, whereas, the bound 99mTc-F4A probe was not displaced by F1A
      (120,000:1). Human plasma interfered with 99mTc-F1A binding to fibrin clot
      (p<0.05) in vitro, whereas, 99mTc-F4A targeting was unaffected. The
      pharmacokinetic half-life of 99mTc-F4A was 28% faster (124+/-41 min) than 99mTc
      F1A (176+/-26 min) with both being bioeliminated through the urinary system with
      negligible liver or spleen biodistribution. In mice with carotid thrombus, 99mTc
      F4A binding to the injured carotid was much greater (16.3+/-3.3 %ID/g, p=0.01)
      than that measured with an irrelevant negative control, 99mTc-I4A (3.4+/-1.6
      %ID/g). In an LVAD mock flow-loop (1:1, PBS:human plasma:heparin) operating at
      maximal flow rate, 99mTc-F4A bound well to phantom clots in 2 min (p<0.05),
      whereas 99mTc-F1A had negligible targeting. Excised LVADs from patients
      undergoing pump exchange or heart transplant were rewired, studied in the mock
      flow loop, and found to have spatially variable fibrin accumulations in the inlet
      and outlet cannulas and bearings. Conclusions:99mTc-F4A is a high-avidity
      prototype probe for characterizing thrombus in LVADs that is anticipated to help
      optimize anticoagulation, reduce thromboembolic events, and minimize pump
      exchange.

PMID- 29464008
TI  - LncRNA PFL contributes to cardiac fibrosis by acting as a competing endogenous
      RNA of let-7d.
AB  - Rationale: Cardiac fibrosis is associated with various cardiovascular diseases
      and can eventually lead to heart failure. Dysregulation of long non-coding RNAs
      (lncRNAs) has recently been recognized as one of the key mechanisms involved in
      cardiac diseases. However, the potential roles and underlying mechanisms of
      lncRNAs in cardiac fibrosis have not been explicitly delineated. Methods and
      Results: Using a combination of in vitro and in vivo studies, we identified a
      lncRNA NONMMUT022555, which is designated as a pro-fibrotic lncRNA (PFL), and
      revealed that PFL is up-regulated in the hearts of mice in response to myocardial
      infarction (MI) as well as in the fibrotic cardiac fibroblasts (CFs). We found
      that knockdown of PFL by adenoviruses carrying shRNA attenuated cardiac
      interstitial fibrosis and improved ejection fraction (EF) and fractional
      shortening (FS) in MI mice. Further study showed that forced expression of PFL
      promoted proliferation, fibroblast-myofibroblast transition and fibrogenesis in
      mice CFs by regulating let-7d, whereas silencing PFL mitigated TGF-beta1-induced
      myofibroblast generation and fibrogenesis. More importantly, PFL acted as a
      competitive endogenous RNA (ceRNA) of let-7d, as forced expression of PFL reduced
      the expression and activity of let-7d. Moreover, let-7d levels were decreased in
      the MI mice and in fibrotic CFs. Inhibition of let-7d resulted in fibrogenesis in
      CFs, whereas forced expression of let-7d abated fibrogenesis through targeting
      platelet-activating factor receptor (Ptafr). Furthermore, overexpression of let
      7d by adenoviruses carrying let-7d precursor impeded cardiac fibrosis and
      improved cardiac function in MI mice. Conclusion: Taken together, our study
      elucidated the role and mechanism of PFL in cardiac fibrosis, indicating the
      potential role of PFL inhibition as a novel therapy for cardiac fibrosis.

PMID- 29464009
TI  - Determination of glycated albumin using boronic acid-derived agarose beads on
      paper-based devices.
AB  - Self-monitoring of glycated albumin (GA), a useful glycemic marker, is an
      established method for preventing diabetes complications. Here, the paper-based
      lateral flow assay devices were developed for the sensitive detection of GA and
      the total human serum albumin (tHSA) in self-monitoring diabetes patients.
      Boronic acid-derived agarose beads were packed into a hole on a lateral flow
      channel. These well-coordinated agarose beads were used to capture GA through
      specific cis-diol interactions and to enhance the colorimetric signals by
      concentrating the target molecules. The devices exhibited large dynamic ranges
      (from 10 MUg/ml to 10 mg/ml for GA and from 10 mg/ml to 50 mg/ml for tHSA) and
      low detection limits (7.1 MUg/ml for GA and 4.7 mg/ml for tHSA), which cover the
      range of GA concentration in healthy plasma, which is 0.21-1.65 mg/ml (0.6%-3%).
      In determining the unknown GA concentrations in two commercial human plasma
      samples, the relative percentage difference between the values found by a
      standard ELISA kit and those found by our developed devices was 2.62% and 8.80%,
      which are within an acceptable range. The measurements of GA and tHSA were
      completed within 20 min for the total sample-to-answer diagnosis, fulfilling the
      demand for rapid analysis. Furthermore, the recovery values ranged from 99.4% to
      110% in device accuracy tests. These results indicate that the developed paper
      based device with boronic acid-derived agarose beads is a promising platform for
      GA and tHSA detection as applied to self-monitoring systems.

PMID- 29464010
TI  - Separation of cancer cells using vortical microfluidic flows.
AB  - Label-free separation of viable cancer cells using vortical microfluidic flows
      has been introduced as a feasible cell collection method in oncological studies.
      Besides the clinical importance, the physics of particle interactions with the
      vortex that forms in a wall-confined geometry of a microchannel is a relatively
      new area of fluid dynamics. In our previous work [Haddadi and Di Carlo, J. Fluid.
      Mech. 811, 436-467 (2017)], we have introduced distinct aspects of inertial flow
      of dilute suspensions over cavities in a microchannel such as breakdown of the
      separatrix and formation of stable limit cycle orbits for finite size polystyrene
      particles. In this work, we extend our experiments to address the engineering
      physics of cancer cell entrapment in microfluidic cavities. We begin by studying
      the effects of the channel width and device height on the morphology of the
      vortex, which has not been discussed in our previous work. The stable limit cycle
      orbits of finite size cancer cells are then presented. We demonstrate effects of
      the separatrix breakdown and the limit cycle formation on the operation of the
      cancer cell separation platform. By studying the flow of dilute cell suspensions
      over the cavities, we further develop the notion of the cavity capacity and the
      relative rate of cell accumulation as optimization criteria which connect the
      device geometry with the flow. Finally, we discuss the proper placement of
      multiple cavities inside a microchannel for improved cell entrapment.

PMID- 29464011
TI  - A microfluidic device to study electrotaxis and dopaminergic system of zebrafish
      larvae.
AB  - The zebrafish is a lower vertebrate model organism offering multiple applications
      for both fundamental and biomedical research into the nervous system from genes
      to behaviour. Investigation of zebrafish larvae's movement in response to various
      stimuli, which involves the dopaminergic system, is of interest in the field of
      sensory-motor integration. Nevertheless, the conventional methods of movement
      screening in Petri dishes and multi-well plates are mostly qualitative,
      uncontrollable, and inaccurate in terms of stimulus delivery and response
      analysis. We recently presented a microfluidic device built as a versatile
      platform for fluid flow stimulation and high speed time-lapse imaging of
      rheotaxis behaviour of zebrafish larvae. Here, we describe for the first time
      that this microfluidic device can also be used to test zebrafish larvae's sense
      of the electric field and electrotaxis in a systemic manner. We further show that
      electrotaxis is correlated with the dopamine signalling pathway in a time of day
      dependent manner and by selectively involving the D2-like dopamine receptors. The
      primary outcomes of this research opens avenues to study the molecular and
      physiological basis of electrotaxis, the effects of known agonist and antagonist
      compounds on the dopaminergic system, and the screen of novel pharmacological
      tools in the context of neurodegenerative disorders. We propose that this
      microfluidic device has broad application potential, including the investigation
      of complex stimuli, biological pathways, behaviors, and brain disorders.

PMID- 29464012
TI  - Erratum: "A microfluidic chip based model for the study of full thickness human
      intestinal tissue using dual flow" [Biomicrofluidics 10, 064101 (2016)].
AB  - [This corrects the article DOI: 10.1063/1.4964813.].

PMID- 29464013
TI  - Velocity-Limiting Control of an Active Handheld Micromanipulator.

PMID- 29464014
TI  - Librarians against scientists: Oncotarget's lesson.

PMID- 29464015
TI  - Anti-miR-17 therapy delays tumorigenesis in MYC-driven hepatocellular carcinoma
      (HCC).
AB  - Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few
      therapeutic options. Genomic amplification and/or overexpression of the MYC
      oncogene is a common molecular event in HCC, thus making it an attractive target
      for drug therapy. Unfortunately, currently there are no direct drug therapies
      against MYC. As an alternative strategy, microRNAs regulated by MYC may be
      downstream targets for therapeutic blockade. MiR-17 family is a microRNA family
      transcriptionally regulated by MYC and it is commonly overexpressed in human
      HCCs. In this study, we performed systemic delivery of a novel lipid nanoparticle
      (LNP) encapsulating an anti-miR-17 oligonucleotide in a conditional transgenic
      mouse model of MYC driven HCC. Treatment with anti-miR-17 in vivo, but not with a
      control anti-miRNA, resulted in significant de-repression of direct targets of
      miR-17, robust apoptosis, decreased proliferation and led to delayed
      tumorigenesis in MYC-driven HCCs. Global gene expression profiling revealed
      engagement of miR-17 target genes and inhibition of key transcriptional programs
      of MYC, including cell cycle progression and proliferation. Hence, anti-miR-17 is
      an effective therapy for MYC-driven HCC.

PMID- 29464016
TI  - Inhibition of the NEDD8 conjugation pathway induces calcium-dependent
      compensatory activation of the pro-survival MEK/ERK pathway in acute
      lymphoblastic leukemia.
AB  - De novo and acquired drug resistance and subsequent relapse remain major
      challenges in acute lymphoblastic leukemia (ALL). We previously identified that
      pevonedistat (TAK-924, MLN4924), a first-in-class inhibitor of NEDD8 activating
      enzyme (NAE), elicits ER stress and has potent in vitro and in vivo efficacy
      against ALL. However, in pevonedistat-treated ALL cell lines, we found consistent
      activation of the pro-survival MEK/ERK pathway, which has been associated with
      relapse and poor outcome in ALL. We uncovered that inhibition of the MEK/ERK
      pathway in vitro and in vivo sensitized ALL cells to pevonedistat. The observed
      synergistic apoptotic effect appears to be mediated by inhibition of the MEK/ERK
      pro-survival cascade leading to de-repression of the pro-apoptotic BIM protein.
      Mechanistically, Ca2+ influx via the Ca2+-release-activated Ca2+ (CRAC) channel
      induced protein kinase C beta2 (PKC-beta2) was responsible for activation of the
      MEK/ERK pathway in pevonedistat-treated ALL cells. Sequestration of Ca2+ using
      BAPTA-AM or blockage of store-operated Ca2+ entry (SOCE) using BTP-2 both
      attenuated the compensatory activation of MEK/ERK signaling in pevonedistat
      treated ALL cells. Pevonedistat significantly altered the expression of Orai1 and
      stromal interaction molecule 1 (STIM1), resulting in significantly decreased
      STIM1 protein levels relative to Orai1. Further, we identified eIF2alpha as an
      important post-transcriptional regulator of STIM1, suggesting that pevonedistat
      induced eIF2alpha de-phosphorylation selectively down-regulates translation of
      STIM1 mRNA. Consequently, our data suggest that pevonedistat potentially
      activates SOCE and promotes Ca2+ influx leading to activation of the MEK/ERK
      pathway by altering the stoichiometric Orai1:STIM1 ratio and inducing ER stress
      in ALL cells.

PMID- 29464017
TI  - Regulation of E-cadherin localization by microtubule targeting agents: rapid
      promotion of cortical E-cadherin through p130Cas/Src inhibition by eribulin.
AB  - Microtubule targeting agents (MTAs) are some of the most effective anticancer
      drugs used to treat a wide variety of adult and pediatric cancers. Building
      evidence suggests that these drugs inhibit interphase signaling events and that
      this contributes to their anticancer actions. The effects of diverse MTAs were
      evaluated following a 2 hour incubation with clinically relevant concentrations
      to test the hypothesis that these drugs rapidly and differentially disrupt
      epithelial-to-mesenchymal transition (EMT)-related signaling. The MTAs rapidly
      promoted the cortical localization of internal pools of E-cadherin in HCC1937
      breast cancer cells, with the most robust effects observed with the microtubule
      destabilizers eribulin and vinorelbine. Cortical E-cadherin localization was also
      promoted by the Src kinase inhibitor dasatinib or by siRNA-mediated depletion of
      the p130Cas scaffold. Mechanistic studies demonstrate that eribulin disrupts the
      interaction between p130Cas and Src, leading to decreased cortical Src
      phosphorylation that precedes the accumulation of cortical E-cadherin. These
      results suggest that microtubules can be actively co-opted by cancer cells to
      inhibit cortical E-cadherin localization, a hallmark of EMT, and provide a direct
      link between the initial disruption of the microtubule network and reversal of
      EMT phenotypes demonstrated by eribulin in long-term studies.

PMID- 29464018
TI  - Ganglioside GM1 contributes to extracellular/intracellular regulation of insulin
      resistance, impairment of insulin signaling and down-stream eNOS activation, in
      human aortic endothelial cells after short- or long-term exposure to TNFalpha.
AB  - Vascular insulin resistance induced by inflammatory cytokines leads to the
      initiation and development of vascular diseases. In humans, circulating TNFalpha
      levels are increased during aging, suggesting a correlation between vascular
      insulin resistance and plasma TNFalpha levels. Currently, the precise molecular
      mechanisms of vascular insulin resistance mediated by TNFalpha are not well
      characterized. We aimed at clarifying whether glycosphingolipids contribute to
      vascular insulin resistance after inflammatory stimulation. In this study, we
      examined vascular insulin resistance using human aortic endothelial cells after
      treatment with different concentrations of TNFalpha for different time intervals
      for mimicking in vivo acute or chronic inflammatory situations. We show that
      ganglioside GM1 levels on cell membranes change depending on time of exposure to
      TNFalpha and its concentration and that the GM1 expression is associated with
      specific extracellular/intracellular regulation of the insulin signaling cascade.
      Furthermore, we provide evidence that factors such as aging and senescence affect
      the regulation of insulin resistance. Our data suggest that GM1 is a key player
      in the induction of vascular insulin resistance after short- or long-term
      exposure to TNFalpha and is a good extracellular target for prevention and cure
      of vascular diseases.

PMID- 29464019
TI  - The involvement of serum exosomal miR-500-3p and miR-770-3p in aging: modulation
      by calorie restriction.
AB  - Recent studies have shown a role for miRNAs in aging and age-related diseases,
      and the modulation of miRNA expression by diet attracts attention as a new
      therapeutic strategy. Here, we focused on identifying specific exosomal miRNAs
      derived from serum of aged rats and the effect of short-term calorie restriction
      (CR) on their expression. Exosomes from serum of young (7-month), old (22-month),
      and old-CR Sprague Dawley rats were isolated and characterized by transmission
      electron microscopy analyses, dynamic light scattering measurements, and Western
      blotting. A total of 12 significantly expressed miRNAs in serum exosomes of young
      and old rats were identified by next generation sequencing. After analysis of qRT
      PCR, we found that miR-500-3p and miR-770-3p expression was significantly
      upregulated by aging and downregulated by CR. Furthermore, receiver operating
      characteristic (ROC) curve revealed that the selected miRNAs represented high
      accuracy in discriminating old rats from young rats. Finally, PANTHER analysis
      predicted selected miRNAs targets genes involved in Wnt/chemokines and cytokines 
      related inflammatory signaling pathway and function as transcription factor. In
      conclusion, our results suggest that the expression of serum exosomal miR-500-3p
      and miR-770-3p was significantly increased with aging, whereas these were
      decreased by CR, and age-/CR-modulated exosomal miR-500-3p and miR-770-3p could
      potentially be used as informative biomarkers candidates for aging.

PMID- 29464020
TI  - MMP2-A2M interaction increases ECM accumulation in aged rat kidney and its
      modulation by calorie restriction.
AB  - Age-associated renal fibrosis is related with renal function decline during
      aging. Imbalance between accumulation and degradation of extracellular matrix is
      key feature of fibrosis. In this study, RNA-sequencing (RNA-Seq) results based on
      next-generation sequencing (NGS) data were analyzed to identify key proteins that
      change during aging and calorie restriction (CR). Among the changed genes, A2M
      and MMP2, which are known to interact, exhibited the highest between centrality
      (BC) and degree values when analyzed by protein-protein interaction (PPI). Both
      mRNA and protein levels of MMP2 and A2M were increased during aging. Furthermore,
      the interaction between MMP2 and A2M was verified by immunoprecipitation and
      immunohistochemistry. MMP2 activity was further measured under the presence or
      absence of A2M-MMP2 interaction. MMP2 activity, which was increased under the
      absence of A2M-MMP2 interaction, was significantly decreased under the presence
      of interactions in aged kidney. We further hypothesized that the interaction
      between A2M-MMP2 played a role in the inactivation of MMP2 leading to
      accumulation of ECM including collagen type I and IV. Aged kidney showed highly
      accumulated MMP2 substrate proteins despite of increased MMP2 protein expression
      and CR blunted these accumulation. Additional in vivo analysis revealed that the
      signal transducer and activator of transcription (STAT) 3 transcriptional factor
      was significantly increased thus increasing A2M expression during aging. STAT3
      activating cytokines were also highly increased in aged kidney. In conclusion,
      the results of the present study indicate that A2M-MMP2 interaction has a role in
      age-associated renal ECM accumulation and in the suppression such fibrosis by CR.

PMID- 29464021
TI  - Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with
      transient ischemic attack and cerebral infarction.
AB  - Transient ischemic attack (TIA) is a predictor for cerebral infarction (CI), and
      early diagnosis of TIA is extremely important for the prevention of CI. We set
      out to identify novel antibody biomarkers for TIA and CI, and detected matrix
      metalloproteinase 1 (MMP1), chromobox homolog 1 (CBX1), and chromobox homolog 5
      (CBX5) as candidate antigens using serological identification of antigens by
      recombinant cDNA expression cloning (SEREX) and Western blotting to confirm the
      presence of serum antibodies against the antigens. Amplified luminescent
      proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) revealed that
      serum antibody levels were significantly higher in patients with TIA or acute
      phase CI (aCI) compared with healthy donors (P < 0.01). Spearman's correlation
      analysis and multivariate logistic regression analysis demonstrated that levels
      of anti-MMP1, anti-CBX1, and anti-CBX5 antibodies were associated with age,
      cigarette-smoking habits, and blood pressure. Thus, serum levels of antibodies
      against MMP1, CBX1, and CBX5 could potentially serve as useful tools for
      diagnosing TIA and predicting the onset of aCI.

PMID- 29464022
TI  - Anticoagulants inhibit proteolytic clearance of plasma amyloid beta.
AB  - We recently discovered a plasma proteolysis pathway, termed the FXII-FVII pathway
      which is composed of coagulation proteases, and found it to be mainly responsible
      for the clearance of Abeta42 in the plasma in mice. Abeta42 and Abeta40 are the
      main Abeta forms in Alzheimer's disease (AD). In the present study, in vitro
      assays, wild type (WT) mice and J20 mice (a transgenic AD model) are used to
      assess the degradation of Abeta40 and Abeta42 by the FXII-FVII pathway and the
      impact of anticoagulants on such degradation. Four clinically available and
      mechanistically distinct anticoagulants are evaluated, including dabigatran,
      enoxaparin (EP), rivaroxaban and warfarin. Each anticoagulant significantly
      elevates plasma level of synthetic Abeta42 in WT mice, among which EP is the most
      effective. The differential efficacies of the anticoagulants in elevating plasma
      Abeta42 level match closely with their inhibitory mechanisms towards the FXII
      FVII pathway. Plasma Abeta40 is also degraded by the FXII-FVII pathway and is
      protected by EP. Moreover, the FXII-FVII pathway is significantly activated in
      J20 mice, but EP inhibits the activation and significantly elevates plasma levels
      of both Abeta40 and Abeta42. Taken together, our results shed new light on Abeta
      metabolism, reveal a novel function of anticoagulants, and suggest a novel
      approach to potentially developing plasma Abeta as an AD biomarker.

PMID- 29464023
TI  - Interferon sensitivity-determining region of hepatitis C virus influences virus
      production and interferon signaling.
AB  - The number of amino acid substitutions in the interferon (IFN) sensitivity
      determining region (ISDR) of hepatitis C virus (HCV) NS5A is a strong predictor
      for the outcome of IFN-based treatment. To assess the involvement of ISDR in the
      HCV life cycle and to clarify the molecular mechanisms influencing IFN
      susceptibility, we used recombinant JFH-1 viruses with NS5A of the genotype 1b
      Con1 strain (JFH1/5ACon1) and with NS5A ISDR containing 7 amino acid
      substitutions (JFH1/5ACon1/i-7mut), and compared the virus propagation and the
      induction of interferon-stimulated genes (ISGs). By transfecting RNAs of these
      strains into HuH-7-derived cells, we found that the efficiency of infectious
      virus production of JFH1/5ACon1/i-7mut was attenuated compared with JFH1/5ACon1.
      After transfecting full-length HCV RNA into HepaRG cells, the mRNA expression of
      ISGs was sufficiently induced by IFN treatment in JFH1/5ACon1/i-7mut-transfected
      but not in JFH1/5ACon1-transfected cells. These data suggested that the NS5A
      mediated inhibition of ISG induction was deteriorated by amino acid substitutions
      in the ISDR. In conclusion, using recombinant JFH-1 viruses, we demonstrated that
      HCV NS5A is associated with infectious virus production and the inhibition of IFN
      signaling, and amino acid substitutions in the NS5A ISDR deteriorate these
      functions. These observations explain the strain-specific evasion of IFN
      signaling by HCV.

PMID- 29464024
TI  - NAB2 is a novel immune stimulator of MDA-5 that promotes a strong type I
      interferon response.
AB  - Novel adjuvants are needed to increase the efficacy of vaccine formulations and
      immune therapies for cancer and chronic infections. In particular, adjuvants that
      promote a strong type I IFN response are required, since this cytokine is crucial
      for the development of efficient anti-tumoral and anti-viral immunity. Nucleic
      acid band 2 (NAB2) is a double-stranded RNA molecule isolated from yeast and
      identified as an agonist of the pattern-recognition receptors TLR3 and MDA-5. We
      compared the ability of NAB2 to activate innate immunity with that of poly(I:C),
      a well-characterized TLR3 and MDA-5 agonist known for the induction of type I
      IFN. NAB2 promoted stronger IFN-alpha production and induced a higher activation
      state of both murine and human innate immune cells compared to poly(I:C). This
      correlated with a stronger activation of the signalling pathway downstream of MDA
      5, and IFN-alpha induction was dependent on MDA-5. Upon injection, NAB2 induced
      higher levels of serum IFN-alpha in mice than poly(I:C). These results suggest
      that NAB2 has the potential to become an efficient adjuvant for the induction of
      type-I IFN responses in therapeutic immunization against cancer or infections.

PMID- 29464025
TI  - Microsatellite instability is a biomarker for immune checkpoint inhibitors in
      endometrial cancer.
AB  - In recent years, it has become evident that tumor cells have immune escape
      mechanisms, and immune checkpoint inhibitor therapy (anti-PD-1/PD-L1 antibody)
      has shown benefit in various cancers. In endometrial tumors with microsatellite
      instability (MSI), somatic mutations have the potential to encode ''non-self''
      immunogenic antigens, and lymphocytes have been shown to infiltrate the tumor.
      Therefore, immune checkpoint inhibitor therapy might be effective in endometrial
      cancers with MSI. Expression of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2,
      and MSH6), the presence of tumor-infiltrating lymphocytes (CD8+), and PD-1/PD-L1
      expression were assessed by immunohistochemistry in 149 patients with endometrial
      cancer. We examined whether tumors with MSI had an enhanced immune
      microenvironment and whether MSI could be a predictor of the therapeutic effect
      of PD-1/PD-L1 immunotherapy in endometrial cancer. Loss of MMR protein expression
      was identified in 42 (28.2%) of 149 patients (MSI group) with endometrial cancer.
      There was no significant relationship between MSI status and age (p = 0.193),
      histological grade (p = 0.097), FIGO stage (p = 0.508), pelvic lymph node
      metastasis (p = 0.139), or depth of myometrial invasion (p = 0.494). However, the
      presence of tumor-infiltrating lymphocytes (CD8+) and PD-L1/PD-1 expression were
      significantly higher in the MSI group compared to the microsatellite-stable group
      (p = 0.002, p = 0.001, and p = 0.008, respectively). These results suggest that
      immune checkpoint inhibitors (anti-PD-1/PD-L1 antibody) could be effective in
      endometrial cancers with MSI. The presence of MSI may be a biomarker for good
      response to PD-1/PD-L1 immunotherapy in endometrial cancer.

PMID- 29464027
TI  - Combining molecular and immunohistochemical analyses of key drivers in primary
      melanomas: interplay between germline and somatic variations.
AB  - Due to the high mutational somatic burden of Cutaneous Malignant Melanoma (CMM) a
      thorough profiling of the driver mutations and their interplay is necessary to
      explain the timing of tumorigenesis or for the identification of actionable
      genetic events. The aim of this study was to establish the mutation rate of some
      of the key drivers in melanoma tumorigenesis combining molecular analyses and/or
      immunohistochemistry in 93 primary CMMs from an Italian cohort also characterized
      for germline status, and to investigate an interplay between germline and somatic
      variants. BRAF mutations were present in 68% of cases, while CDKN2A germline
      mutations were found in 16 % and p16 loss in tissue was found in 63%. TERT
      promoter somatic mutations were detected in 38% of cases while the TERT -245T>C
      polymorphism was found in 51% of cases. NRAS mutations were found in 39% of BRAF
      negative or undetermined cases. NF1 was expressed in all cases analysed. MC1R
      variations were both considered as a dichotomous variable or scored. While a
      positive, although not significant association between CDKN2A germline mutations,
      but not MC1R variants, and BRAF somatic mutation was found, we did not observe
      other associations between germline and somatic events. A yet undescribed inverse
      correlation between TERT -245T>C polymorphism and the presence of BRAF mutation
      was found. It is possible to hypothesize that -245T>C polymorphism could be
      included in those genotypes which may influence the occurrence of BRAF mutations.
      Further studies are needed to investigate the role of -245T>C polymorphism as a
      germline predictor of BRAF somatic mutation status.

PMID- 29464026
TI  - Converging blockchain and next-generation artificial intelligence technologies to
      decentralize and accelerate biomedical research and healthcare.
AB  - The increased availability of data and recent advancements in artificial
      intelligence present the unprecedented opportunities in healthcare and major
      challenges for the patients, developers, providers and regulators. The novel deep
      learning and transfer learning techniques are turning any data about the person
      into medical data transforming simple facial pictures and videos into powerful
      sources of data for predictive analytics. Presently, the patients do not have
      control over the access privileges to their medical records and remain unaware of
      the true value of the data they have. In this paper, we provide an overview of
      the next-generation artificial intelligence and blockchain technologies and
      present innovative solutions that may be used to accelerate the biomedical
      research and enable patients with new tools to control and profit from their
      personal data as well with the incentives to undergo constant health monitoring.
      We introduce new concepts to appraise and evaluate personal records, including
      the combination-, time- and relationship-value of the data. We also present a
      roadmap for a blockchain-enabled decentralized personal health data ecosystem to
      enable novel approaches for drug discovery, biomarker development, and
      preventative healthcare. A secure and transparent distributed personal data
      marketplace utilizing blockchain and deep learning technologies may be able to
      resolve the challenges faced by the regulators and return the control over
      personal data including medical records back to the individuals.

PMID- 29464028
TI  - Consecutive epigenetically-active agent combinations act in ID1-RUNX3-TET2 and
      HOXA pathways for Flt3ITD+ve AML.
AB  - Co-occurrence of Flt3ITD and TET2 mutations provoke an animal model of AML by
      epigenetic repression of Wnt pathway antagonists, including RUNX3, and by
      hyperexpression of ID1, encoding Wnt agonist. These affect HOXA over-expression
      and treatment resistance. A comparable epigenetic phenotype was identified among
      adult AML patients needing novel intervention. We chose combinations of targeted
      agents acting on distinct effectors, at the levels of both signal transduction
      and chromatin remodeling, in relapsed/refractory AML's, including Flt3ITD+ve,
      described with a signature of repressed tumor suppressor genes, involving Wnt
      antagonist RUNX3, occurring along with ID1 and HOXA over-expressions. We tracked
      patient response to combination of Flt3/Raf inhibitor, Sorafenib, and Vorinostat,
      pan-histone deacetylase inhibitor, without or with added Bortezomib, in
      consecutive phase I trials. A striking association of rapid objective remissions
      (near-complete, complete responses) was noted to accompany induced early
      pharmacodynamic changes within patient blasts in situ, involving these effectors,
      significantly linking RUNX3/Wnt antagonist de-repression (80%) and ID1
      downregulation (85%), to a response, also preceded by profound HOXA9 repression.
      Response occurred in context of concurrent TET2 mutation/hypomorphy and
      Flt3ITD+ve mutation (83% of complete responses). Addition of Bortezomib to the
      combination was vital to attainment of complete response in Flt3ITD+ve cases
      exhibiting such Wnt pathway dysregulation.

PMID- 29464029
TI  - The protein kinase SIK downregulates the polarity protein Par3.
AB  - The multifunctional cytokine transforming growth factor beta (TGFbeta) controls
      homeostasis and disease during embryonic and adult life. TGFbeta alters
      epithelial cell differentiation by inducing epithelial-mesenchymal transition
      (EMT), which involves downregulation of several cell-cell junctional
      constituents. Little is understood about the mechanism of tight junction
      disassembly by TGFbeta. We found that one of the newly identified gene targets of
      TGFbeta, encoding the serine/threonine kinase salt-inducible kinase 1 (SIK),
      controls tight junction dynamics. We provide bioinformatic and biochemical
      evidence that SIK can potentially phosphorylate the polarity complex protein
      Par3, an established regulator of tight junction assembly. SIK associates with
      Par3, and induces degradation of Par3 that can be prevented by proteasomal and
      lysosomal inhibition or by mutation of Ser885, a putative phosphorylation site on
      Par3. Functionally, this mechanism impacts on tight junction downregulation.
      Furthermore, SIK contributes to the loss of epithelial polarity and examination
      of advanced and invasive human cancers of diverse origin displayed high levels of
      SIK expression and a corresponding low expression of Par3 protein. High SIK mRNA
      expression also correlates with lower chance for survival in various carcinomas.
      In specific human breast cancer samples, aneuploidy of tumor cells best
      correlated with cytoplasmic SIK distribution, and SIK expression correlated with
      TGFbeta/Smad signaling activity and low or undetectable expression of Par3. Our
      model suggests that SIK can act directly on the polarity protein Par3 to regulate
      tight junction assembly.

PMID- 29464030
TI  - Under-expression of CK2beta subunit in ccRCC represents a complementary biomarker
      of p-STAT3 Ser727 that correlates with patient survival.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype
      of renal cancer. STAT3 pathway is altered in these tumors and p-STAT3 Ser727 is
      an independent prognostic factor for ccRCC. Protein kinase CK2 is altered in
      different types of tumors and overexpression of CK2alpha is considered predictive
      of bad prognosis and metastatic risk. CK2 subunits analyses in ccRCC samples
      showed increased CK2alpha/alpha' nuclear content in all cases, but decreased
      cytosolic CK2beta (CK2betacyt) levels in the more advanced tumors. Stable
      downregulation of CK2beta in renal proximal tubular (HK-2) and clear cell
      adenocarcinoma (786-O) cells triggered changes in E-cadherin, vimentin and Snail1
      protein levels indicative of epithelial-to-mesenchymal transition (EMT), and
      increased HIF-alpha. Moreover, CK2beta was required in order to observe STAT3
      Ser727 phosphorylation in HK-2 but not in 786-O cells. We also observed that
      CK2beta improved the prognostic value of p-STAT3 Ser727, as CK2betacyt>41 (median
      value) discriminates patients free of disease for a period of 10 years upon
      surgery, from those with CK2betacyt<41, when p-STAT3 Ser727levels are low. We
      conclude that CK2beta down-regulation might represent a mechanism to support EMT
      and angiogenesis and that CK2betacyt levels are instrumental to refine prognosis
      of ccRCC patients with low p-STAT3 Ser727 levels.

PMID- 29464031
TI  - Phospholipase Cgamma1 links inflammation and tumorigenesis in colitis-associated
      cancer.
AB  - : Colorectal cancer (CRC) is the third diagnosed cancer and the second leading
      cause of cancer-related deaths in the United States. Colorectal cancer is linked
      to inflammation and phospholipase Cgamma1 (PLCgamma1) is associated with
      tumorigenesis and the development of colorectal cancer; however, evidence of
      mechanisms connecting them remains unclear. The tight junctions (TJ), as
      intercellular junctional complexes, have an important role for integrity of the
      epithelial barrier to regulate the cellular permeability. Here we found that
      PLCgamma1 regulated colitis and tumorigenesis in intestinal epithelial cells
      (IEC). To induce the colitis-associated cancer (CAC), we used the AOM/DSS model.
      Mice were sacrificed at 100 days (DSS three cycles) and 120 days (DSS one cycle).
      In a CAC model, we showed that the deletion of PLCgamma1 in IEC decreased the
      incidence of tumors by enhancing apoptosis and inhibiting proliferation during
      tumor development. Accordingly, the deletion of PLCgamma1 in IEC reduced colitis
      induced epithelial inflammation via inhibition of pro-inflammatory cytokines and
      mediators. The PLCgamma1 pathway in IEC accelerated colitis-induced epithelial
      damage via regulation of TJ proteins. CONCLUSIONS: Our findings suggest that
      PLCgamma1 is a critical regulator of colitis and colorectal cancer and could
      further help in the development of therapy for colitis-associated cancer.

PMID- 29464032
TI  - Stroma-derived extracellular vesicles deliver tumor-suppressive miRNAs to
      pancreatic cancer cells.
AB  - The biology of tumor-associated stroma (TAS) in pancreatic ductal adenocarcinoma
      (PDAC) is not well understood. The paradoxical observation that stroma-depletion
      strategies lead to progression of PDAC reinforced the need to critically evaluate
      the functional contribution of TAS in the initiation and progression of PDAC.
      PDAC and TAS cells are unique in their expression of specific miRNAs, and this
      specific miRNA expression pattern alters host to tumor microenvironment
      interactions. Using primary human pancreatic TAS cells and primary xenograft PDAC
      cells co-culture, we provide evidence of miRNA trafficking and exchanging between
      TAS and PDAC cells, in a two-way, cell-contact independent fashion, via
      extracellular vesicles (EVs) transportation. Selective packaging of miRNAs into
      EVs led to enrichment of stromal specific miR-145 in EVs secreted by TAS cells.
      Exosomes, but not microvesicles, derived from human TAS cells demonstrated a
      tumor suppressive role by inducing PDAC cell apoptosis. This effect was mitigated
      by anti-miR-145 sequences. Our data suggest that TAS-derived miRNAs are delivered
      to adjacent PDAC cells via exosomes and suppress tumor cell growth. These data
      highlight that TAS cells secrete exosomes carrying tumor suppressive genetic
      materials, a possible anti-tumor capacity. Future work of the development of
      patient-derived exosomes could have therapeutic implications for unresectable
      PDAC.

PMID- 29464033
TI  - Long-term prediction of prostate cancer diagnosis and death using PSA and obesity
      related anthropometrics at early middle age: data from the malmo preventive
      project.
AB  - Objectives: To evaluate whether anthropometric parameters add to PSA measurements
      in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and
      death. Results: After adjusting for PSA, both BMI and weight were significantly
      associated with an increased risk of PCa death with the odds of a death
      corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p =
      0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs
      did not meaningfully increase with the addition of weight or BMI to prediction
      models including PSA. Materials and Methods: In 1974 to 1986, 22,444 Swedish men
      aged 44 to 50 enrolled in Malmo Preventive Project, Sweden, and provided blood
      samples and anthropometric data. Rates of PSA screening in the cohort were very
      low. Documentation of PCa diagnosis and disease-specific death up to 2014 was
      retrieved through national registries. Among men with anthropometric measurements
      available at baseline, a total of 1692 men diagnosed with PCa were matched to
      4190 controls, and 464 men who died of disease were matched to 1390 controls.
      Multivariable conditional logistic regression was used to determine whether
      diagnosis or death from PCa were associated with weight and body mass index (BMI)
      at adulthood after adjusting for PSA. Conclusions: Men with higher BMI and weight
      at early middle age have an increased risk of PCa diagnosis and death after
      adjusting for PSA. However, in a multi-variable numerical statistical model, BMI
      and weight do not importantly improve the predictive accuracy of PSA. Risk
      stratification of screening should be based on PSA without reference to
      anthropometrics.

PMID- 29464034
TI  - Analysis of the circular RNA transcriptome in endometrial cancer.
AB  - Circular RNAs (circRNAs) are a naturally occurring family of non-coding RNA that
      may regulate gene expression in mammals. circRNAs are more stable than messenger
      RNAs due to their resistance to RNA exonuclease. A growing body of evidence has
      shown that the expression of circRNAs is regulated during development in a tissue
      specific manner. CircRNAs have been implicated in a number of cancers; however,
      their role in endometrial cancer (EC) is completely unknown. Here, we report the
      circular transcriptome specific for EC as determined by RNA sequencing. We found
      that the overall abundance of circRNAs is lower in EC than in normal endometrium.
      Further, there are numerous 'hotspot' genes from which circRNAs are transcribed
      that may account for alterations in circRNA expression between the normal and
      malignant endometrium. Most importantly, we have also identified circRNAs that
      are differentially expressed between malignant and normal endometrial tissue. The
      functional significance of these circRNAs in cancer remains to be determined, but
      they may serve as potential biomarkers for the diagnosis of EC or monitoring of
      EC progression.

PMID- 29464035
TI  - Upregulation of cell cycle genes in head and neck cancer patients may be
      antagonized by erufosine's down regulation of cell cycle processes in OSCC cells.
AB  - The TCGA database was analyzed to identify deregulation of cell cycle genes
      across 24 cancer types and ensuing effects on patient survival. Pan-cancer
      analysis showed that head and neck squamous cell carcinoma (HNSCC) ranks amongst
      the top four cancers showing deregulated cell cycle genes. Also, the median gene
      expression of all CDKs and cyclins in HNSCC patient samples was higher than that
      of the global gene expression. This was verified by IHC staining of CCND1 from
      HNSCC patients. When evaluating the quartiles with highest and lowest expression,
      increased CCND1/CDK6 levels had negative implication on patient survival. In
      search for a drug, which may antagonize this tumor profile, the potential of the
      alkylphosphocholine erufosine was evaluated against cell lines of the HNSCC
      subtype, oral squamous cell carcinoma (OSCC) using in-vitro and in-vivo assays.
      Erufosine inhibited growth of OSCC cell lines concentration dependently. Initial
      microarray findings revealed that cyclins and CDKs were down-regulated
      concentration dependently upon exposure to erufosine and participated in negative
      enrichment of cell cycle processes. These findings, indicating a pan-cdk/cyclin
      inhibition by erufosine, were verified at both, mRNA and protein levels.
      Erufosine caused a G2/M block and inhibition of colony formation. Significant
      tumor growth retardation was seen upon treatment with erufosine in a xenograft
      model. For the decreased cyclin D1 and CDK 4/6 levels found in tumor tissue,
      these proteins can serve as biomarker for erufosine intervention. The findings
      demonstrate the potential of erufosine as cell cycle inhibitor in HNSCC
      treatment, alone or in combination with current therapeutic agents.

PMID- 29464036
TI  - Breast cancer stem cells in HER2-negative breast cancer cells contribute to HER2
      mediated radioresistance and molecular subtype conversion: clinical implications
      for serum HER2 in recurrent HER2-negative breast cancer.
AB  - Although it has been proposed that the beneficial effect of HER2-targeted therapy
      in HER2-negative breast cancer is associated with the molecular subtype
      conversion, the underlying mechanism and the clinical biomarkers are unclear. Our
      study showed that breast cancer stem cells (BCSCs) mediated HER2 subtype
      conversion and radioresistance in HER2-negative breast cancer cells and evaluated
      serum HER2 as a clinical biomarker for HER2 subtype conversion. We found that the
      CD44+/CD24-/low BCSCs from HER2-negative breast cancer MCF7 cells overexpressed
      HER2 and EGFR and showed the radioresistant phenotype. In addition, we showed
      that trastuzumab treatment sensitized the radioresistant phenotype of the
      CD44+/CD24-/low cells with decreased levels of HER2 and EGFR, which suggested
      that HER2-targeted therapy in HER2-negative breast cancer could be useful for
      targeting BCSCs that overexpress HER2/EGFR. Importantly, our clinical data showed
      that serial serum HER2 measurement synchronously reflected the disease relapse
      and the change in tumor burden in some patients who were initially diagnosed as
      HER2-negative breast cancer, which indicated that serum HER2 could be a clinical
      biomarker for the evaluation of HER2 subtype conversion in patients with
      recurrent HER2-negative breast cancer. Therefore, our data have provided in vitro
      and in vivo evidence for the molecular subtype conversion of HER2-negative breast
      cancer.

PMID- 29464037
TI  - Comparison of the modified low-dose cytarabine and etoposide with decitabine
      therapy for elderly acute myeloid leukemia patients unfit for intensive
      chemotherapy.
AB  - To overcome unsatisfactory results of classical low-dose cytarabine (LDAC) of
      cytarabine <=20 mg twice daily (BID) subcutaneously for 10 days for patients with
      elderly acute myeloid leukemia (eAML), we evaluated a modified LDAC (mLDAC) of
      cytarabine 20 mg/m2 BID subcutaneously plus etoposide 50 mg BID orally for 14
      days. To determine its feasibility, we compared outcomes of 77 and 42 eAML
      patients who received, respectively, mLDAC and decitabine (DAC; 20 mg/m2
      intravenously daily for 5 days), which has shown better outcomes compared to
      those of classical LDAC. Most of baseline characteristics of two groups were well
      balanced. The mLDAC group had a higher complete response (CR) rate compared to
      the DAC group (46.8% vs. 19.0%, P < 0.01). Unlike the classical LDAC, mLDAC
      induced CR in patients with adverse cytogenetics, with its rate similar to that
      of the DAC group (33.3% vs. 20.0%; P = 0.58). Meanwhile, mucositis, neutropenic
      fever and invasive aspergillosis were more frequently observed in the mLDAC
      group, with no difference in early mortality between two groups (P > 0.05). The
      median overall survival rates of the mLDAC and DAC groups were comparable (8.7 vs
      8.3 months, respectively, P = 0.35), presumably because the advantage of higher
      CR rate in the mLDAC group was offset by beneficial effects of marrow response,
      which is observed dominantly in the DAC group. Our results suggested that the
      outcomes of classical LDAC could be improved by modest modifications, to be
      comparable to those of DAC.

PMID- 29464038
TI  - The influence of chemotherapy on adenosine-producing B cells in patients with
      head and neck squamous cell carcinoma.
AB  - Introduction: Head and neck squamous cell carcinoma (HNSCC) strongly suppresses
      the immune system, resulting in increased metastasis and recurrent disease.
      Chemotherapy is part of the multimodal treatment but may further
      immunosuppression. Recently, we demonstrated that regulatory B cells (Breg),
      defined as CD19+CD39+CD73+ B cells, play a significant role in the production of
      immunosuppressive, extracellular adenosine (ADO). Here, we tested the influence
      of chemotherapy on Breg function. Results: In HNSCC patients, Breg were
      diminished in absolute number and frequency after chemotherapy (paired samples).
      Chemotherapeutic drugs had variable effects; while platinum-based chemotherapy
      decreased the expression of CD39, methotrexate led to a functional increase in
      CD39 expression and increased production of immunosuppressive ADO. These findings
      were confirmed in a second patient cohort. Surface expression of CD39 correlated
      strongly with the production of ADO as measured by mass spectrometry.
      Conclusions: Platinum-based anti-tumor-therapy reduces the number of adenosine
      producing B cells and, consequently, potential immunosuppression within the tumor
      environment. Breg function in terms of ADO production and their potential
      capacity to suppress CD4+ T cells are promoted by methotrexate treatment
      amplifying anti-inflammatory therapeutic effects. Our results add to the
      understanding of how chemotherapeutic drugs can influence the human immune system
      and may therefore help to orchestrate standard oncologic therapy with new immune
      modulating approaches. Methods: Mononuclear cells were collected prospectively
      from HNSCC patients before and after chemotherapy (n = 18), from healthy donors
      (n = 20), and an additional cohort sampled several months after chemotherapy (n =
      14). Frequency, phenotype, and function of Breg were determined by multicolor
      flow cytometry, ATP luminescence assay as well as mass spectrometry measuring 5'
      AMP, ADO, and inosine. Isolated B cells were incubated with chemotherapeutic
      drugs (cisplatin, methotrexate, paclitaxel, 5-fluorouracil) in vitro for
      functional studies.

PMID- 29464039
TI  - High RAC3 expression levels are required for induction and maintaining of cancer
      cell stemness.
AB  - RAC3 is a transcription coactivator, usually overexpressed in several tumors and
      required to maintain the pluripotency in normal stem cells. In this work we
      studied the association between RAC3 overexpression on cancer cell stemness and
      the capacity of this protein to induce cancer stem properties in non tumoral
      cells. We performed in vitro and in vivo experiments using two strategies: by
      overexpressing RAC3 in the non tumoral cell line HEK293 and by silencing RAC3 in
      the human colorectal epithelial cell line HCT116 by transfection. Furthermore, we
      analysed public repository microarrays data from human colorectal tumors in
      different developmental stages. We found that RAC3 overexpression was mainly
      associated to CD133+ side-population of colon cancer cells and also to early and
      advanced stages of colon cancer, involving increased expression of mesenchymal
      and stem markers. In turn, RAC3 silencing induced diminished tumoral properties
      and cancer stem cells as determined by Hoechst efflux, tumorspheres and
      clonogenic growth, which correlated with decreased Nanog and OCT4 expression. In
      non tumoral cells, RAC3 overexpression induced tumoral transformation;
      mesenchymal phenotype and stem markers expression. Moreover, these transformed
      cells generated tumors in vivo. Our results demonstrate that RAC3 is required for
      maintaining and induction of cancer cell stemness.

PMID- 29464040
TI  - Activation of Grm1 expression by mutated BRaf (V600E) in vitro and in vivo.
AB  - Our laboratory previously showed that ectopic expression of Grm1 is sufficient to
      induce spontaneous melanoma formation with 100% penetrance in transgenic mouse
      model, TG-3, which harbors wild-type BRaf. Studies identified Grm1 expression in
      human melanoma cell lines and primary to secondary metastatic melanoma biopsies
      having wild-type or mutated BRaf, but not in normal melanocytes or benign nevi.
      Grm1 expression was detected in tissues from mice genetically engineered with
      inducible melanocyte-specific BRafV600E. Additionally, stable clones derived from
      introduction of exogenous BRafV600E in mouse melanocytes also showed Grm1
      expression, which was not detected in the parental or empty vector-derived cells,
      suggesting that expression of BRafV600E could activate Grm1 expression. Despite
      aberrant Grm1 expression in the inducible, melanocyte-specific BRafV600E mice, no
      tumors formed. However, in older mice, the melanocytes underwent senescence, as
      demonstrated previously by others. It was proposed that upregulated p15 and
      TGFbeta contributed to the senescence phenotype. In contrast, in older TG-3 mice
      the levels of p15 and TGFbeta remained the same or lower. Taken together, these
      results suggest the temporal regulation on the expression of "oncogenes" such as
      Grm1 or BRafV600E is critical in the future fate of the cells. If BRafV600E is
      turned on first, Grm1 expression can be induced, but this is not sufficient to
      result in development of melanoma; the cells undergo senescence. In contrast, if
      ectopic expression of Grm1 is turned on first, then regardless of wild-type or
      mutated BRaf in the melanocytes melanoma development is the consequence.

PMID- 29464041
TI  - Inhibition of NF-kappaB prevents the acidic bile-induced oncogenic mRNA
      phenotype, in human hypopharyngeal cells.
AB  - Bile-containing gastro-duodenal reflux has been clinically considered an
      independent risk factor in hypopharyngeal carcinogenesis. We recently showed that
      the chronic effect of acidic bile, at pH 4.0, selectively induces NF-kappaB
      activation and accelerates the transcriptional levels of genes, linked to head
      and neck cancer, in normal hypopharyngeal epithelial cells. Here, we hypothesize
      that NF-kappaB inhibition is capable of preventing the acidic bile-induced and
      cancer-related mRNA phenotype, in treated normal human hypopharyngeal cells. In
      this setting we used BAY 11-7082, a specific and well documented pharmacologic
      inhibitor of NF-kappaB, and we observed that BAY 11-7082 effectively inhibits the
      acidic bile-induced gene expression profiling of the NF-kappaB signaling pathway
      (down-regulation of 72 out of 84 analyzed genes). NF-kappaB inhibition
      significantly prevents the acidic bile-induced transcriptional activation of NF
      kappaB transcriptional factors, RELA (p65) and c-REL, as well as genes related to
      and commonly found in established HNSCC cell lines. These include anti-apoptotic
      bcl-2, oncogenic STAT3, EGFR, ?Np63, TNF-alpha and WNT5A, as well as cytokines IL
      1beta and IL-6. Our findings are consistent with our hypothesis demonstrating
      that NF-kappaB inhibition effectively prevents the acidic bile-induced cancer
      related mRNA phenotype in normal human hypopharyngeal epithelial cells supporting
      an understanding that NF-kappaB may be a critical link between acidic bile and
      early preneoplastic events in this setting.

PMID- 29464042
TI  - YAP-associated chromosomal instability and cholangiocarcinoma in mice.
AB  - Deregulated Hippo pathway signaling is associated with aberrant activation of the
      downstream effector yes-associated protein (YAP), an emerging key oncogenic
      mediator in cholangiocarcinoma (CCA). In our prior work, we have demonstrated
      that biliary transduction of YAP along with Akt as a permissive factor induces
      CCA in mice. To further delineate the mechanisms associated with YAP-associated
      biliary oncogenesis, we have established seven malignant murine cell lines from
      our YAP-driven murine CCA model. These cells express the CCA markers SRY (Sex
      Determining Region Y)-Box 9 (SOX9), cytokeratin (CK)-7 and 19 but lack hepatocyte
      nuclear factor 4 alpha and alpha-smooth muscle actin, markers of hepatocellular
      carcinoma and cancer-associated fibroblasts, respectively. Notably, the murine
      CCA cells can be readily implanted into mouse livers with resultant orthotopic
      tumor formation. In this unique syngeneic orthotopic murine model, tumors exhibit
      histopathologic features resembling human CCA. We analyzed transcriptome data
      from YAP-associated parent CCA tumor nodules and identified a gene expression
      pattern associated with chromosomal instability, known as CIN25. Similarly, mate
      pair sequencing of the murine CCA cells revealed chromosomal missegregation with
      gains and losses of several whole chromosomes demonstrating aneuploidy. Of the
      CIN25 genes, forkhead box M1 (Foxm1), a key cell cycle regulator, was the most
      significantly upregulated CIN25 gene product. Accordingly, small interfering RNA
      (siRNA)-mediated silencing of YAP as well as FOXM1 inhibition with thiostrepton
      induced CCA cell death. These preclinical data imply a role for YAP-mediated
      chromosomal instability in cholangiocarcinoma, and suggest FOXM1 inhibition as a
      therapeutic target for CCA.

PMID- 29464043
TI  - Zinc finger protein 598 inhibits cell survival by promoting UV-induced apoptosis.
AB  - UV is one of the major causes of DNA damage induced apoptosis. However, cancer
      cells adopt alternative mechanisms to evade UV-induced apoptosis. To identify
      factors that protect cancer cells from UV-induced apoptosis, we performed a
      genome wide short-hairpin RNA (shRNA) screen, which identified Zinc finger
      protein 598 (ZNF598) as a key regulator of UV-induced apoptosis. Here, we show
      that UV irradiation transcriptionally upregulates ZNF598 expression.
      Additionally, ZNF598 knockdown in cancer cells inhibited UV-induced apoptosis. In
      our study, we observe that ELK1 mRNA level as well as phosphorylated ELK1 levels
      was up regulated upon UV irradiation, which was necessary for UV irradiation
      induced upregulation of ZNF598. Cells expressing ELK1 shRNA were also resistant
      to UV-induced apoptosis, and phenocopy ZNF598 knockdown. Upon further
      investigation, we found that ZNF598 knockdown inhibits UV-induced apoptotic gene
      expression, which matches with decrease in percentage of annexin V positive cell.
      Similarly, ectopic expression of ZNF598 promoted apoptotic gene expression and
      also increased annexin V positive cells. Collectively, these results demonstrate
      that ZNF598 is a UV irradiation regulated gene and its loss results in resistance
      to UV-induced apoptosis.

PMID- 29464044
TI  - The transcriptional and mutational landscapes of lipid metabolism-related genes
      in colon cancer.
AB  - Metabolic alterations encountered in tumors are well recognized and considered as
      a hallmark of cancer. In addition to Warburg Effect, epidemiological and
      experimental studies support the crucial role of lipid metabolism in colorectal
      cancer (CRC). The overexpression of four lipid metabolism-related genes (ABCA1,
      ACSL1, AGPAT1 and SCD genes) has been proposed as prognostic marker of stage II
      CRC (ColoLipidGene signature). In order to explore in depth the transcriptomic
      and genomic scenarios of ABCA1, ACSL1, AGPAT1 and SCD genes, we performed a
      transcriptomic meta-analysis in more than one thousand CRC individuals.
      Additionally we analyzed their genomic coding sequence in 95 patients, to find
      variants that could orchestrate CRC prognosis. We found that genetic variant
      rs3071, located on SCD gene, defines a 9.77% of stage II CRC patients with high
      risk of death. Moreover, individuals with upregulation of ABCA1 and AGPAT1
      expression have an increased risk of CRC recurrence, independently of tumor
      stage. ABCA1 emerges as one of the main contributors to signature's prognostic
      effect. Indeed, both high ABCA1 expression and presence of tumoral genetic
      variants located in ABCA1 coding region, seem to be associated with CRC risk of
      death. In addition the non-synonymous polymorphism rs2230808, located on ABCA1,
      is associated with gene expression. Patients carrying at least one copy of minor
      allele showed higher levels of ABCA1 expression than patients carrying homozygous
      major allele. This study broaden the prognostic value of ABCA1, ACSL1, AGPAT1 and
      SCD genes, independently of CRC tumor stage, leading to future precision medicine
      approaches and "omics"-guided therapies.

PMID- 29464045
TI  - Pathological and functional significance of Semaphorin-5A in pancreatic cancer
      progression and metastasis.
AB  - Semaphorin-5A (SEMA5A) has differential cell surface expression between normal
      and cancer cells and represents an attractive target for therapeutic intervention
      in pancreatic cancer (PC). In this study, we delineated the pathological
      expression and significance of SEMA5A during PC progression and metastasis. We
      utilized human tissue microarrays and different PC mouse models (Pdx1-cre; LSL-
      Kras(G12D), Pdx1-Cre; LSL-Kras(G12D); LSL-p53(R172H) and RIP1-Tag2) to analyze
      SEMA5A expression during PC progression. Using human patients and different mouse
      models, we demonstrated that SEMA5A expression was highest in liver metastases,
      followed by primary pancreatic tumors, and the lowest expression was found in the
      normal pancreas. SEMA5A expression was localized on tumor cells with no staining
      in the surrounding stroma. To understand the functional significance of SEMA5A,
      we treated PC cell lines with recombinant SEMA5A. We observed an increase in
      migration, chemotaxis, and scattering of PC cells. To delineate the signaling
      axis of SEMA5A, we generated SEMA5A receptor-Plexin-B3 knockdown in T3M-4 and
      CD18/HPAF PC cell lines and observed that the effect of SEMA5A treatment was
      absent in the Plexin-B3 knockdown counterparts of T3M-4 and CD18/HPAF cells.
      SEMA5A treatment leads to phosphorylation of cMET in Plexin-B3 dependent manner.
      Our data demonstrate that there is an increase in SEMA5A expression during PC
      progression and the elevation of this expression takes place at metastatic sites
      especially the liver in both exocrine and endocrine tumors. SEMA5A can elicit a
      migratory response in cells by activating cMET through the Plexin-B3 receptor. In
      conclusion, SEMA5A signaling represents a potential molecule for targeting
      metastasis in pancreatic cancer.

PMID- 29464046
TI  - Identification and characterization of novel enhanced cell penetrating peptides
      for anti-cancer cargo delivery.
AB  - Cell penetrating peptides (CPP) are able cross the membrane and to transport
      cargos, presenting a great potential in drug delivery and diagnosis. In this
      paper, we have identified novel natural or synthetic CPPs. We have validated
      their rapid and efficient time and dose-dependent penetration, the absence of
      toxicity, the intracellular localization and the stability to proteases
      degradation, one of the main bottlenecks of peptides. Moreover, we have associate
      a cargo (an interfering peptide blocking the association of the serine/threonine
      phosphatase PP2A to its inhibitor, the oncogene SET) to the new generated
      shuttles and showed that they new bi-functional peptides keep the original
      properties of the shuttle and, in addition, are able to induce apoptosis due to
      the properties of the cargo. The CPPs identified in this study have promising
      perspectives for future anti-cancer drug delivery.

PMID- 29464047
TI  - A dock derived compound against laminin receptor (37 LR) exhibits anti-cancer
      properties in a prostate cancer cell line model.
AB  - Laminin receptor (67 LR) is a 67 kDa protein derived from a 37 kDa precursor (37
      LR). 37/67 LR is a strong clinical correlate for progression, aggression, and
      chemotherapeutic relapse of several cancers including breast, prostate, and
      colon. The ability of 37/67 LR to promote cancer cell aggressiveness is further
      increased by its ability to transduce physiochemical and mechanosensing signals
      in endothelial cells and modulate angiogenesis. Recently, it was demonstrated
      that 37/67 LR modulates the anti-angiogenic potential of the secreted
      glycoprotein pigment epithelium-derived factor (PEDF). Restoration of PEDF
      balance is a desirable therapeutic outcome, and we sought to identify a small
      molecule that could recapitulate known signaling properties of PEDF but without
      the additional complications of peptide formulation or gene delivery safety
      validation. We used an in silico drug discovery approach to target the
      interaction interface between PEDF and 37 LR. Following cell based counter
      screening and binding validation, we characterized a hit compound's anti
      viability, activation of PEDF signaling-related genes, anti-wound healing, and
      anti-cancer signaling properties. This hit compound has potential for future
      development as a lead compound for treating tumor growth and inhibiting
      angiogenesis.

PMID- 29464048
TI  - Src is the primary target of aripiprazole, an atypical antipsychotic drug, in its
      anti-tumor action.
AB  - Aripiprazole (ARP) is an atypical anti-psychotic drug widely used to treat
      schizophrenia and bipolar disorder. The pharmacological effects of ARP on cancer
      cells are still poorly understood. In this study, anti-cancer effects of ARP on
      various malignant tumor cells and its molecular mechanism were further carefully
      examined by using cell proliferation assay, xenograft mouse model, immunoblotting
      analysis, migration assay, luciferase reporter gene assay, kinase assay, and
      overexpression strategy. Treatment with ARP induced cytotoxicity in U251 glioma
      cells, MKN-1 gastric adenosquamous carcinoma cells, and CT26 colon carcinoma
      cells. ARP suppressed cell proliferation of LN428, MDA-MB-231, and HEK293 cells.
      Pro-apoptotic factors active caspase-3, -8, and -9, as well as p53, were
      upregulated, whereas the protein and mRNA levels of anti-apoptotic factor B-cell
      lymphoma 2 (Bcl-2) decreased. In agreement with the in vitro results, ARP
      compound also significantly suppressed the growth of tumor masses formed by
      injecting CT26 colon cancer cells into mice. ARP treatment also effectively
      decreased the migratory ability of U251 glioma cells by downregulating
      metalloproteinase-9. Levels of phosphorylated Src, phosphorylated
      phosphatidylinositide 3-kinase (PI3K), and phosphorylated signal transducer and
      activator of transcription 3 (STAT3) were significantly decreased following ARP
      treatment. ARP compound reduced the kinase activity of Src. Our studies suggest
      that Src may be an important target molecule linked to the antitumor effects of
      ARP.

PMID- 29464049
TI  - Inhibition of IAP's and activation of p53 leads to caspase-dependent apoptosis in
      gastric cancer cells treated with Scutellarein.
AB  - Gastric cancer is the fifth most common cancer and the third leading cause of
      cancer deaths worldwide. South Korea is in first place with 9,180 death alone
      attributed to gastric cancer in 2013. Plenty of literature suggests the evasion
      of apoptosis is implicated in neurodegeneration, autoimmune diseases, and tumors
      development due to dysregulation in the apoptotic mechanism. Reduced apoptosis or
      its resistance in cancer cells plays a significant role in carcinogenesis. It's
      imperative to understand apoptosis, which provides the basis for novel targeted
      therapies that can induce cancer cell death or sensitize them to cytotoxic agents
      by regulating key factors like IAPs, MDM2, p53, caspases and much more. Studies
      have demonstrated that Scutellarein have the ability to inhibit several cancer
      cells by inducing apoptosis with both: Scutellarein monomers as well as
      scutellarein containing flavonoids. MTT results revealed that scutellarein
      inhibited cell viability in both dose and time dependent manner. Flow cytometry
      and western blot analysis showed that scutellarein induces apoptosis in both AGS
      and SNU-484 human gastric cancer cells and G2/M phase cell cycle arrest in SNU
      484 cells. This study demonstrated that the Scutellarein on AGS and SNU-484 cells
      significantly inhibits cell proliferation and induces apoptotic cell death via
      down regulating MDM2 and activated the tumor suppresser protein p53, subsequently
      down regulating the IAP family proteins (cIAP1, cIAP2, and XIAP) leading to
      caspase-dependent apoptosis in AGS and SNU-484 cells.

PMID- 29464050
TI  - Assessing tumor molecular profiling to guide treatments for patients with
      advanced female genital tract malignancy.
AB  - Tumor molecular profiling has enabled selection of targeted therapies in a host
      of solid tumors. Here we used a retrospective clinical cohort, to evaluate the
      benefit of tailoring treatments for female genital tract malignancy, using tumor
      molecular profiles. Clinical outcome data for 112 patients was retrospectively
      separated into two groups. These either followed a matched treatment plan that
      incorporated at least one drug recommended according to their tumor profile and
      none that were expected to have no benefit (64 patients), or was unmatched with
      suggested treatments and received at least one drug that was anticipated to lack
      benefit for that tumor (48 patients). In the group of patients whose drugs
      matched those recommended by molecular profiling of their tumor, their overall
      survival was 593 days on average, compared to 449 days for patients that did not;
      removing drugs predicted to have no benefit from treatment regimens received
      after profiling increased survival by 144 days on average (P = 0.0265). In the
      matched treatment group, 30% of patients had died by the last time of monitoring,
      whereas this was 40% in the unmatched group (P = 0.2778). The IHC biomarker for
      the progesterone receptor was demonstrated to be prognostic for survival.

PMID- 29464051
TI  - Human papillomavirus E7 oncoprotein expression by keratinocytes alters the
      cytotoxic mechanisms used by CD8 T cells.
AB  - Cervical cancer is a malignant transformation of keratinocytes initiated by the
      E7 oncoprotein of human papillomavirus (HPV). These tumors are characterized by
      keratinocyte hyperproliferation and are often infiltrated with activated CD8 T
      cells. HPV infection confers changes to gain immunological advantage to promote
      chronic infection, and these persist with malignant transformation. We
      investigated the relative importance of the many redundant mechanisms of
      cytotoxicity used by CD8 T cells to kill keratinocytes expressing HPV E7
      oncoprotein using extended-duration time-lapse microscopy that allows examination
      of cell-to-cell interactions during killing. E7 expression by keratinocytes
      increased susceptibility to cell-mediated killing. However, while killing of non
      transgenic keratinocytes was traditional, perforin-mediated, and caspase
      dependent, E7-expression favored killing by perforin-independent, caspase
      independent mechanisms. The roles of perforin, TNFalpha, IFNgamma, Fas/FasL and
      PD1/PD-L1 were graded according to target cell survival to produce a hierarchy of
      killing mechanisms utilized in killing E7-expressing cells. TNFalpha was
      essential for perforin-mediated killing of E7-expressing cells, but not perforin
      independent killing. IFNgamma facilitated killing by Fas/FasL interaction,
      especially in the absence of perforin. Additionally, expression of E7 offered
      protection from killing by up regulation of PD-L1, Fas and FasL expression on
      keratinocytes promoting fight-back by target cells, resulting in effector cell
      death. This study shows that keratinocytes expressing E7 are highly susceptible
      to killing by CD8 T cells, but utilizing different armamentarium. Down-regulation
      of CD8 T cell cytotoxicity in HPV-related tumors may be due to suppression by E7
      expressing keratinocytes. Immunotherapy for HPV-related cancers may be improved
      by suppression of PD-L1, or by suppression of FasL.

PMID- 29464052
TI  - Epigenetic changes found in uterine decidual and placental tissues can also be
      found in the breast cancer microenvironment of the same unique patient:
      description and potential interpretations.
AB  - Microenvironmental properties are thought to be responsible for feto-maternal
      tolerance. Speculatively, ectopic expression of placental gene programs might
      also be related to cancer cells' ability to escape from immune vigilance
      mechanisms during carcinogenesis and cancer progression. Recently, we published
      the first human genomic evidence of similar immune related gene expression
      profiles in both placenta (placenta and decidual tissue) and cancer (both primary
      and metastatic) in the same patient with lymph-node positive breast carcinoma
      during pregnancy. Here we report the first epigenomic analysis of these tissue
      samples and describe their main findings, with respect to immune related genes
      regulation (over or under expressed) in cancer cells with regards placental
      tissues. We confirm significant similarities, and hierarchical clustering (both
      unsupervised and supervised), in CpG island methylation patterns between
      decidual/placental and cancer microenvironments, which cannot be easily explained
      by simple models or unique pathways. Several different cell types are probably
      involved in these complex immune regulation mechanisms. Cancers may somehow
      "hijack" gene programs evolved over millions of years to allow for feto-maternal
      tolerance in placental mammals in order to escape from immune vigilance and
      spread locally or to distant sites.

PMID- 29464053
TI  - Combination of a thioxodihydroquinazolinone with cisplatin eliminates ovarian
      cancer stem cell-like cells (CSC-LCs) and shows preclinical potential.
AB  - Cancer stem cell-like cells (CSC-LCs) contribute to drug resistance and
      recurrence of ovarian cancer. Strategies that can eradicate CSC-LCs are expected
      to substantially improve the outcome of ovarian cancer treatment. We have
      previously identified a class of thioxodihydroquinazolinone small molecules,
      which have strong synergistic antitumor activity with platinum drugs, the
      standard chemotherapeutic agents for ovarian cancer treatment. In the current
      study, using the activity of aldehyde dehydrogenase (ALDH) as a marker of CSC
      LCs, we demonstrated that the combination of thioxodihydroquinazolinone compound
      19 with cisplatin is able to diminish ALDH-high CSC-LC populations in both
      platinum-resistant ovarian cancer cell lines and primary ovarian cancer cells
      from metastatic ascites of a cisplatin-resistant patient. Compound 19 enhanced
      the accumulation of intracellular cisplatin in ALDH-high ovarian CSC-LCs. The
      combination of compound 19 with cisplatin was also able to reduce the sphere
      forming capability of cisplatin-resistant ovarian cancer cells. Using a spheroid
      based in vitro metastasis model of ovarian cancer, we demonstrated that the co
      administration of compound 19 with cisplatin prevents ovarian cancer spheroid
      cells from attaching to substratum and spreading. In a cisplatin-resistant in
      vivo intraperitoneal xenograft mouse model, the combination of compound 19 with
      cisplatin significantly reduced tumor burden, as compared to cisplatin alone.
      Taken together, our study demonstrated that thioxodihydroquinazolinones represent
      a new class of agents that in combination with cisplatin are capable of
      eliminating CSC-LCs in ovarian cancer. Further development of
      thioxodihydroquinazolinone small molecules may yield a more effective treatment
      for cisplatin-resistant metastatic ovarian cancer.

PMID- 29464054
TI  - Rapid development of myeloproliferative neoplasm in mice with Ptpn11D61Y mutation
      and haploinsufficient for Dnmt3a.
AB  - PTPN11 gain-of-function mutation is the most common mutation found in patients
      with juvenile myelomonocytic leukemia and DNMT3A loss occurs in over 20% of acute
      myeloid leukemia patients. We studied the combined effect of both Ptpn11 gain-of
      function mutation (D61Y) and Dnmt3a haploinsufficiency on mouse hematopoiesis,
      the presence of which has been described in both juvenile myelomonocytic leukemia
      and acute myeloid leukemia patients. Double mutant mice rapidly become moribund
      relative to any of the other genotypes, which is associated with enlargement of
      the spleen and an increase in white blood cell counts. An increase in the mature
      myeloid cell compartment as reflected by the presence of Gr1+Mac1+ cells was also
      observed in double mutant mice relative to any other group. Consistent with these
      observations, a significant increase in the absolute number of granulocyte
      macrophage progenitors (GMPs) was seen in double mutant mice. A decrease in the
      lymphoid compartment including both T and B cells was noted in the double mutant
      mice. Another significant difference was the presence of extramedullary
      erythropoiesis with increased erythroid progenitors in the spleens of Dnmt3a+/
      ;D61Y mice relative to other groups. Taken together, our results suggest that the
      combined haploinsufficiency of Dnmt3a and presence of an activated Shp2 changes
      the composition of multiple hematopoietic lineages in mice relative to the
      individual heterozygosity of these genes.

PMID- 29464055
TI  - [Neratinib + Valproate] exposure permanently reduces ERBB1 and RAS expression in
      4T1 mammary tumors and enhances M1 macrophage infiltration.
AB  - The irreversible ERBB1/2/4 inhibitor neratinib has been shown in vitro to rapidly
      reduce the expression of ERBB1/2/4 and RAS proteins via autophagic/lysosomal
      degradation. We have recently demonstrated that neratinib and valproate interact
      to suppress the growth of 4T1 mammary tumors but had not defined whether the
      [neratinib + valproate] drug combination, in a mouse, had altered the biology of
      the 4T1 cells. Exposure of 4T1 mammary tumors to [neratinib + valproate] for
      three days resulted, two weeks later, in tumors that expressed less ERBB1, K-RAS,
      N-RAS, indoleamine-pyrrole 2,3-dioxygenase (IDO-1), ornithine decarboxylase (ODC)
      and had increased Class I MHCA expression. Tumors previously exposed to
      [neratinib + valproate] grew more slowly than those exposed to vehicle control
      and contained more CD8+ cells and activated NK cells. M1 but not M2 macrophage
      infiltration was significantly enhanced by the drug combination. In vitro
      exposure of 4T1 tumor cells to [neratinib + valproate] variably reduced the
      expression of histone deacetylases 1-11. In vivo, prior exposure of tumors to
      [neratinib + valproate] permanently reduced the expression of HDACs 1-3, 6 and
      10. Combined knock down of HDACs 1/2/3 or of 3/10 rapidly reduced the expression
      IDO-1, and ODC and increased the expression of MHCA. H&E staining of normal
      tissues at animal nadir revealed no obvious cyto-architectural differences
      between control and drug-treated animals. We conclude that [neratinib +
      valproate] evolves 4T1 tumors to grow more slowly and to be more sensitive to
      checkpoint immunotherapy antibodies.

PMID- 29464056
TI  - Expression of Wnt-signaling pathway genes and their associations with miRNAs in
      colorectal cancer.
AB  - The Wnt-signaling pathway functions in regulating cell growth and thus is
      involved in the carcinogenic process of several cancers, including colorectal
      cancer. We tested the hypothesis that multiple genes in this signaling pathway
      are dysregulated and that miRNAs are associated with these dysregulated genes. We
      used data from 217 colorectal cancer (CRC) cases to evaluate differences in Wnt
      signaling pathway gene expression between paired CRC and normal mucosa and
      identify miRNAs that are associated with these genes. Gene expression data from
      RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were
      analyzed. We focused on genes most strongly associated with CRC (fold change (FC)
      of >1.5 or <0.67) and that were statistically significant after adjustment for
      multiple comparisons. Of the 138 Wnt-signaling pathway genes examined, 27 were
      significantly down-regulated (FC<0.67) and 32 genes were significantly up
      regulated (FC>1.50) after adjusting for multiple comparisons. Thirteen of the 66
      Wnt-signaling genes that were differentially expressed in CRC tumors were
      associated with differential expression of miRNAs. A total of 93 miRNA:mRNA
      associations were detected for these 13 genes. Of these 93 associations, 36 miRNA
      seed-region matches were observed, suggesting that miRNAs have both direct and
      indirect effects on Wnt-signaling pathway genes. In summary, our data supports
      the hypothesis that the Wnt-signaling pathway is dysregulated in CRC and suggest
      that miRNAs may importantly influence that dysregulation.

PMID- 29464057
TI  - Construction of key signal regulatory network in metastatic colorectal cancer.
AB  - There are many stages in the development and metastasis of colorectal cancer
      (CRC). In this study, we compared the differential expression genes in different
      stages of metastatic CRC. Then, we screened the continuously up-regulated genes
      and the continuously down-regulated genes that were associated with the
      development and metastasis of CRC. After analyzing the intersection of
      differential expression genes in each stage, we screened the continuously up
      regulated genes and deviated genes in the extracellular matrix and the
      continuously down-regulated genes and deviated genes in the mitochrondia of CRC.
      Then, we performed gene ontology enrichment analysis of the deviated genes in
      different phases, and we found that key molecular events occurred in the period
      extending from stage II to III (early stage of metastasis) of CRC. Furthermore,
      in this period we found that the chemotaxis of inflammatory cells had decreased
      in the extracellular matrix. On the other hand, the aerobic respiration had
      increased in the mitochondrion. Then, we constructed protein-protein interaction
      network of deviated genes in the extracellular matrix and mitochondrion. We used
      the network module and hub network to analyze the protein-protein interaction
      network. The network module analysis showed that the protein complex of VEGFA and
      CCL7-CCR3 is the key node in the extracellular matrix, while MAPK1 is the key
      node in the mitochondrion. The hub network analysis showed that the signal
      transmission chain FN1->SPARC->COL1A1->MMP2 is the key regulatory pathway for
      extracellular signal transmission. Furthermore, it also showed that CAV1->MAPK3
      >RAF1->NR3C1->MAPK1->ESR1 is the key regulatory pathway for signal transmission
      in mitochondrion.

PMID- 29464058
TI  - Type IIB DNA topoisomerase is downregulated by trastuzumab and doxorubicin to
      synergize cardiotoxicity.
AB  - Despite heightened risk of cardiotoxicity associated with combination therapy of
      anthracyclines and trastuzumab in HER2-positive breast cancer patients, little
      research effort has been invested in exploring the molecular mechanisms of
      cardiotoxicity induced by this combination therapy. In this study, we demonstrate
      that trastuzumab downregulates both gene and protein expressions of type IIB DNA
      topoisomerase/DNA topoisomerase IIB (TOP2B), a major intracellular target
      mediating doxorubicin-induced cardiotoxicity, in human primary cardiomyocytes.
      This in turn induces DNA damage activity and DNA double strand breaks, which is
      indicated by the enhanced phosphorylation of H2AX (gammaH2AX) and ataxia
      telangiectasia and Rad3-related protein (ATR pS428) in trastuzumab-treated
      cardiomyocytes. Furthermore, concurrent or sequential treatment of doxorubicin
      and trastuzumab significantly increases the downregulation of the protein levels
      of TOP2B, enhances apoptosis and cell growth inhibition, and promotes production
      of reactive oxidative and nitrative species in human cardiomyocytes as compared
      to either trastuzumab or doxorubicin treatment, indicating augmentation of
      cardiotoxicity in combination therapy. Additionally, our data reveal that
      doxorubicin treatment increases the levels of ErbB2/HER2 expression in human
      cardiomyocytes as compared with that in cells not treated with doxorubicin,
      leading to the enhanced activity downstream of HER2 signaling. Consequently, this
      may render the cardiomyocytes to become addicted to HER2 signaling for survival
      under stressed conditions. Enhanced HER2 protein expression leaves cardiomyocytes
      more sensitive to trastuzumab treatment after doxorubicin exposure. This study
      provides molecular basis for significantly increased cardiotoxicity in cancer
      patients who are treated with anthracyclines and trastuzumab-based combination
      regimens.

PMID- 29464059
TI  - Characterization and metabolic synthetic lethal testing in a new model of SDH
      loss familial pheochromocytoma and paraganglioma.
AB  - Succinate dehydrogenase (SDH)-loss pheochromocytoma and paraganglioma (PPGL) are
      tumors driven by metabolic derangement. SDH loss leads to accumulation of
      intracellular succinate, which competitively inhibits dioxygenase enzymes,
      causing activation of pseudohypoxic signaling and hypermethylation of histones
      and DNA. The mechanisms by which these alterations lead to tumorigenesis are
      unclear, however. In an effort to fundamentally understand how SDH loss
      reprograms cell biology, we developed an immortalized mouse embryonic fibroblast
      cell line with conditional disruption of Sdhc and characterize the kinetics of
      Sdhc gene rearrangement, SDHC protein loss, succinate accumulation, and the
      resultant hypoproliferative phenotype. We further perform global transcriptomic,
      epigenomic, and proteomic characterization of changes resulting from SDHC loss,
      identifying specific perturbations at each biological level. We compare the
      observed patterns of epigenomic derangement to another previously-described
      immortalized mouse chromaffin cell model of SDHB loss, and compare both models to
      human SDH-loss tumors. Finally, we perform analysis of SDHC synthetic lethality
      with lactate dehydrogenase A (LDHA) and pyruvate carboxylase (PCX), which are
      important for regeneration of NAD+ and aspartate biosynthesis, respectively. Our
      data show that SDH-loss cells are selectively vulnerable to LDH genetic knock
      down or chemical inhibition, suggesting that LDH inhibition may be an effective
      therapeutic strategy for SDH-loss PPGL.

PMID- 29464060
TI  - Drp1/Fis1 interaction mediates mitochondrial dysfunction, bioenergetic failure
      and cognitive decline in Alzheimer's disease.
AB  - Mitochondrial dynamics, involving a balance between fusion and fission, regulates
      mitochondrial quality and number. Increasing evidence suggests that dysfunctional
      mitochondria play a role in Alzheimer's disease (AD). We observed that Drp1
      interaction with one of the adaptors, Fis1, is significantly increased in Abeta
      treated neurons and AD patient-derived fibroblasts. P110, a seven-amino acid
      peptide, which specifically inhibits Drp1/Fis1 interaction without affecting the
      interaction of Drp1 with its other adaptors, attenuated Abeta42-induced
      mitochondrial recruitment of Drp1 and prevented mitochondrial structural and
      functional dysfunction in cultured neurons, in cells expressing mutant amyloid
      precursor protein (KM670/671NL), and in five different AD patient-derived
      fibroblasts. Importantly, sustained P110 treatment significantly improved
      behavioral deficits, and reduced Abeta accumulation, energetic failure and
      oxidative stress in the brain of the AD mouse model, 5XFAD. This suggests that
      Drp1/Fis1 interaction and excessive mitochondrial fission greatly contribute to
      Abeta-mediated and AD-related neuropathology and cognitive decline. Therefore,
      inhibiting excessive Drp1/Fis1-mediated mitochondrial fission may benefit AD
      patients.

PMID- 29464061
TI  - Natural and molecular history of prolactinoma: insights from a Prlr-/- mouse
      model.
AB  - Lactotroph adenoma, also called prolactinoma, is the most common pituitary tumor
      but little is known about its pathogenesis. Mouse models of prolactinoma can be
      useful to better understand molecular mechanisms involved in abnormal lactotroph
      cell proliferation and secretion. We have previously developed a prolactin
      receptor deficient (Prlr-/- ) mouse, which develops prolactinoma. The present
      study aims to explore the natural history of prolactinoma formation in Prlr-/-
      mice, using hormonal, radiological, histological and molecular analyses to
      uncover mechanisms involved in lactotroph adenoma development. Prlr-/- females
      develop large secreting prolactinomas from 12 months of age, with a penetrance of
      100%, mimicking human aggressive densely granulated macroprolactinoma, which is a
      highly secreting subtype. Mean blood PRL measurements reach 14 902 ng/mL at 24
      months in Prlr-/- females while PRL levels were below 15 ng/mL in control mice (p
      < 0.01). By comparing pituitary microarray data of Prlr-/- mice and an estrogen
      induced prolactinoma model in ACI rats, we pinpointed 218 concordantly
      differentially expressed (DE) genes involved in cell cycle, mitosis, cell
      adhesion molecules, dopaminergic synapse and estrogen signaling. Pathway/gene-set
      enrichment analyses suggest that the transcriptomic dysregulation in both models
      of prolactinoma might be mediated by a limited set of transcription factors
      (i.e., STAT5, STAT3, AhR, ESR1, BRD4, CEBPD, YAP, FOXO1) and kinases (i.e., JAK2,
      AKT1, BRAF, BMPR1A, CDK8, HUNK, ALK, FGFR1, ILK). Our experimental results and
      their bioinformatic analysis provide insights into early genomic changes in
      murine models of the most frequent human pituitary tumor.

PMID- 29464062
TI  - Cell-cell fusion as a mechanism of DNA exchange in cancer.
AB  - Cell-cell fusion describes the process by which two cells combine their plasma
      membranes and become a single cell, possessing and retaining certain genetic
      information from each parent cell. Here, using a Cre-loxP-based method initially
      developed to investigate extracellular vesicle targeting, we found that cancer
      cells spontaneously and rapidly deliver DNA to non-cancer cells in vitro via a
      cell-cell fusion event. The resulting hybrid cells were aneuploid and possessed
      enhanced clonal diversity and chemoresistance compared to non-hybrid cancer
      cells. We also observed cell-cell fusion to occur in vivo between melanoma cells
      and non-cancer cells of both hematopoietic and non-hematopoietic lineages. These
      findings suggest that cell-cell fusion occurs during the natural progression of
      cancer and show that this mechanism has the potential to cause massive genomic
      alterations that are observed in cancer. Furthermore, these findings somewhat
      contradict recent publications suggesting that the Cre-loxP method measures only
      extracellular vesicle-mediated intercellular communication.

PMID- 29464063
TI  - Combined inhibition of CDK and HDAC as a promising therapeutic strategy for both
      cutaneous and uveal metastatic melanoma.
AB  - Very little to no improvement in overall survival has been seen in patients with
      advanced non-resectable cutaneous melanoma or metastatic uveal melanoma in
      decades, highlighting the need for novel therapeutic options. In this study we
      investigated as a potential novel therapeutic intervention for both cutaneous and
      uveal melanoma patients a combination of the broad spectrum HDAC inhibitor
      quisinostat and pan-CDK inhibitor flavopiridol. Both drugs are currently in
      clinical trials reducing time from bench to bedside. Combining quisinostat and
      flavopiridol shows a synergistic reduction in cell viability of all melanoma cell
      lines tested, irrespective of their driver mutations. This synergism was also
      observed in BRAFV600E mutant melanoma that had acquired resistance to BRAF
      inhibition. Mechanistically, loss of cell viability was, at least partly, due to
      induction of apoptotic cell death. The combination was also effectively inducing
      tumor regression in a preclinical setting, namely a patient-derived tumor
      xenograft (PDX) model of cutaneous melanoma, without increasing adverse effects.
      We propose that the quisinostat/flavopiridol combination is a promising
      therapeutic option for both cutaneous and uveal metastatic melanoma patients,
      independent of their mutational status or (acquired) resistance to BRAF
      inhibition.

PMID- 29464064
TI  - Translational study reveals a two-faced role of RBM3 in pancreatic cancer and
      suggests its potential value as a biomarker for improved patient stratification.
AB  - Periampullary adenocarcinoma, including pancreatic cancer, is a heterogeneous
      group of tumors with dismal prognosis, partially due to lack of reliable
      targetable and predictive biomarkers. RNA-binding motif protein 3 (RBM3) has
      previously been shown to be an independent prognostic and predictive biomarker in
      several types of cancer. Herein, we examined the prognostic value of RBM3 in
      periampullary adenocarcinoma, as well as the effects following RBM3 suppression
      in pancreatic cancer cells in vitro. RBM3 mRNA levels were examined in 176
      pancreatic cancer patients from The Cancer Genome Atlas. Immunohistochemical
      expression of RBM3 was analyzed in tissue microarrays with primary tumors and
      paired lymph node metastases from 175 consecutive patients with resected
      periampullary adenocarcinoma. Pancreatic cancer cells were transfected with anti
      RBM3 siRNA in vitro and the influence on cell viability following chemotherapy,
      transwell migration and invasion was assessed. The results demonstrated that high
      mRNA-levels of RBM3 were significantly associated with a reduced overall survival
      (p = 0.026). RBM3 protein expression was significantly higher in lymph node
      metastases than in primary tumors (p = 0.005). High RBM3 protein expression was
      an independent predictive factor for the effect of adjuvant chemotherapy and an
      independent negative prognostic factor in untreated patients (p for interaction =
      0.003). After siRNA suppression of RBM3 in vitro, pancreatic cancer cells
      displayed reduced migration and invasion compared to control, as well as a
      significantly increased resistance to chemotherapy. In conclusion, the strong
      indication of a positive response predictive effect of RBM3 expression in
      pancreatic cancer may be highly relevant in the clinical setting and merits
      further validation.

PMID- 29464065
TI  - The presence of PD-1 positive tumor infiltrating lymphocytes in triple negative
      breast cancers is associated with a favorable outcome of disease.
AB  - Triple negative breast cancer patients have a poor course of disease not least
      because of limited treatment options however immunotherapy by targeting the PD
      1/PD-L1 checkpoint system is a promising strategy to improve the outcome. Here we
      systematically investigated the expression of PD-1 on tumor infiltrating
      lymphocytes and PD-L1 on both tumor and infiltrated immune cells. Moreover, the
      PD-L1 gene status in tumor cells was assessed. 103 tissue microarray samples
      derived from triple negative breast cancer specimens were immunohistochemically
      stained against PD-1 and PD-L1. Dual marker fluorescence in-situ hybridization
      was applied to the PD-L1 gene and centromere region of chromosome 9. The disease
      free and overall survival rates were determined as a function of the PD-1/PD-L1
      status. A slight gain of the PD-L1 gene region was found in 55% of all samples
      but an elevated PD-L1/cen9 ratio was rather rare (7%). An increased gene dose is
      not associated with an enhanced protein expression and the PD-L1 expression only
      weakly correlates with the amount of immune cell infiltration. Instead, we found
      an association of PD-L1 expression on tumor and immune cells, respectively.
      Notably, the PD-1 expression on immune cells is associated with a favorable
      disease free and overall survival. PD-1 expression indicates an enhanced
      immunological anti-tumor activity and represents a favorable prognostic impact. A
      deeper understanding of factors that affect the regulation and function of the PD
      1/PD-L1 system is required to establish predictive variables and to utilize the
      system for therapeutic intervention of triple negative breast cancer patients.

PMID- 29464066
TI  - Near infrared fluorescence imaging of EGFR expression in vivo using IRDye800CW
      nimotuzumab.
AB  - Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR)
      monoclonal antibody that is approved in many countries for the treatment of EGFR
      positive cancers. Near infrared (NIR) fluorescent dye-labeled antibodies
      represent an attractive class of image-guided surgical probes because of their
      high specificity, tumor uptake, and low dissociation from tumor cells that
      express the antigen. In this study, we developed a NIR fluorescent dye-labeled
      nimotuzumab immunoconjugate, IRDye800CW-nimotuzumab, and evaluated in vitro
      binding with EGFR-positive cells, in vivo tumor uptake by NIR fluorescent
      imaging, and ex vivo biodistribution. There was no difference in binding between
      nimotuzumab and IRDye800CW-nimotuzumab to EGFR-positive cells. In mice bearing
      EGFR-positive xenografts, IRDye800CW-nimotuzumab uptake peaked at 4 days post
      injection and slowly decreased thereafter with high levels of accumulation still
      observed at 28 days post injection. In EGFR-positive xenografts, IRDye800CW
      nimotuzumab showed more than 2-fold higher uptake in tumors compared to
      IRDye800CW-cetuximab. In addition, liver uptake of IRDye800CW-nimotuzumab was two
      fold lower than cetuximab. The lower liver uptake of IRDye800CW-nimotuzumab could
      have implications on the selected dose for clinical trials of the
      immunoconjugate. In summary, this study shows that nimotuzumab is a good
      candidate for NIR fluorescent imaging and image-guided surgery.

PMID- 29464067
TI  - Gene aberration profile of tumors of adolescent and young adult females.
AB  - There has been little improvement in the prognosis for adolescent and young adult
      (AYA) tumor patients. Hence, there is an urgent need to understand the etiology
      of tumor development and identify actionable gene aberrations to improve
      prevention and therapy. Here, 76 sporadic tumors (48 breast, 22 ovarian, and six
      uterine) from 76 AYA females (age range, 25-39 years) were subjected to whole
      exome and RNA sequencing to determine their mutational signatures and actionable
      gene profiles. Two individuals with breast cancer (4.2% of cases) and one with
      ovarian cancer (5.3% of cases) carried germline BRCA2 mutations. The two cases
      with breast tumors also each carried an additional deleterious germline mutation:
      one in TP53 and the other in CHEK2. Mutational signature analysis of the 76
      tumors indicated that spontaneous deamination of 5-methylcytosine and activity of
      the APOBEC cytidine deaminase protein family are major causes of mutagenesis. In
      addition, 18 breast or ovarian tumors (18/70, 26%), including the three cases
      with germline BRCA2 mutations, exhibited a predominant "BRCAness" mutational
      signature, an indicator of functional BRCA1/BRCA2 deficiency. Actionable
      aberrations and high tumor mutation burdens were detected in 24 breast (50%), 17
      ovarian (77%), and five uterine (83%) tumor cases. Thus, mutational processes and
      aberrant genes in AYA tumors are largely shared with those identified in non-AYA
      tumors. The efficacy of molecular targeting and immune checkpoint inhibitory
      therapies should be explored for both AYA and non-AYA patients.

PMID- 29464068
TI  - Prognostic significance of heparanase expression in primary and metastatic breast
      carcinoma.
AB  - High levels of heparanase are detected in many types of tumors, associated with
      bad prognosis. Typically, heparanase levels are evaluated in a biopsy taken from
      the primary lesion, whereas its expression by the resulting metastases is most
      often unresolved. This becomes critically important as anti-heparanase compounds
      enter advanced clinical trials. Here, we examined the expression of heparanase in
      pairs of primary and the resulting distant metastases of breast carcinoma.
      Interestingly, we found that heparanase expression in the metastatic lesion does
      not always reflect its expression in the primary tumor. Accordingly, in some
      cases, the primary lesion was stained positive for heparanase while the
      metastasis stained negative, and vice versa. Heparanase discordance occurred in
      38% of the patients, higher than that reported for hormone receptors, and was
      associated with bad prognosis. Thus, examination of heparanase levels in the
      tumor metastases should be evaluated for most efficient precision medicine
      applying heparanase inhibitors. Furthermore, we found that in stage I breast
      cancer patients strong heparanase staining is associated with shorter overall
      survival. Thus, heparanase levels can assist in the diagnosis and in determining
      the necessity and type of treatment in early stage breast cancer.

PMID- 29464069
TI  - Determination of candidate metabolite biomarkers associated with recurrence of
      HCV-related hepatocellular carcinoma.
AB  - Hepatitis C virus (HCV) infection is associated with a high risk of developing
      hepatocellular carcinoma (HCC) and HCC recurrence remains the primary threat to
      outcomes after curative therapy. In this study, we compared recurrent and non
      recurrent HCC patients treated with radiofrequency ablation (RFA) in order to
      identify characteristic metabolic profile variations associated with HCC
      recurrence. Gas chromatography-mass spectrometry (GC-MS) -based metabolomic
      analyses were conducted on serum samples obtained before and after RFA therapy.
      Significant variations were observed in metabolites in the glycerolipid,
      tricarboxylic acid (TCA) cycle, fatty acid, and amino acid pathways between
      recurrent and non-recurrent patients. Observed differences in metabolites
      associated with recurrence did not coincide before and after treatment except for
      fatty acids. Based on the comparison of serum metabolomes between recurrent and
      non-recurrent patients, key discriminatory metabolites were defined by a random
      forest (RF) test. Two combinations of these metabolites before and after RFA
      treatment showed outstanding performance in predicting HCV-related HCC
      recurrence, they were further confirmed by an external validation set. Our study
      showed that the determined combination of metabolites may be potential biomarkers
      for the prediction of HCC recurrence before and after RFA treatment.

PMID- 29464070
TI  - 2-Amino-3-methylcarboxy-5-heptyl-thiophene (TJ191) is a selective anti-cancer
      small molecule that targets low TbetaRIII-expressing malignant T-cell
      leukemia/lymphoma cells.
AB  - Current chemotherapy regimens often include non-specific cytostatic/cytotoxic
      drugs, which do not distinguish between normal and tumor cells, therefore causing
      considerable systemic toxicity. We previously reported the synthesis and anti
      proliferative activity of a novel synthetic 2-aminothiophene-3-carboxylic acid
      ester derivative TJ191 that selectively targets certain cancer cells without
      affecting the proliferation of other cancer cells or normal fibroblasts or immune
      cells (over 600-fold selectivity). In a panel of ten human T-cell
      leukemia/lymphoma cell lines and peripheral blood mononuclear cells (PBMCs), we
      now found that transforming growth factor beta type III receptor (TbetaRIII)
      expression correlates inversely with TJ191 sensitivity, but not with sensitivity
      against classical chemotherapeutic drugs, thus serving as a predictive marker for
      TJ191 sensitivity. Accordingly, CRISPR/Cas9-mediated knock-out of TbetaRIII
      partially restored the susceptibility of TJ191-resistant cells to this novel
      compound. Our findings highlight TJ191 as a potent and selective anti-cancer
      molecule with pronounced activity against human malignant T-cells expressing low
      levels of TbetaRIII.

PMID- 29464071
TI  - Activation of p53 and destabilization of androgen receptor by combinatorial
      inhibition of MDM2 and MDMX in prostate cancer cells.
AB  - Castration-resistant prostate cancer (CRPC) frequently develops after initial
      standard radiation and androgen deprivation therapy, leaving patients with
      limited further treatment options. Androgen receptor (AR) is a transcription
      factor that plays a key role in the initiation and progression of prostate
      cancer. p53, a major tumor suppressor that is rarely mutated in early-stages of
      prostate cancer, is often deregulated during prostate cancer progression. Here,
      we report an unusual co-amplification of MDM2 and MDMX, two crucial negative
      regulators of p53, in CRPC datasets. We demonstrate that combinatorial inhibition
      of MDM2 and MDMX, with nutlin-3 and NSC207895 respectively, has a profound
      inhibitory effect on cell proliferation of androgen-responsive, wild-type TP53
      gene carrying prostate cancer cells LNCaP and 22Rv1. We further show that the
      combinatorial inhibition of MDM2 and MDMX not only activates p53, but also
      decreases cellular levels of AR and represses its function. Additionally, co
      expression of MDM2 and MDMX stabilizes AR. Together, our results indicate that
      combinatorial inhibition of MDM2 and MDMX may offer a novel compelling strategy
      for prostate cancer therapy.

PMID- 29464072
TI  - LIMD1 is induced by and required for LMP1 signaling, and protects EBV-transformed
      cells from DNA damage-induced cell death.
AB  - LIMD1 (LIM domain-containing protein 1) is considered as a tumor suppressor,
      being deregulated in many cancers to include hematological malignancies; however,
      very little is known about the underlying mechanisms of its deregulation and its
      roles in carcinogenesis. Epstein-Barr Virus (EBV) is associated with a panel of
      malignancies of lymphocytic and epithelial origin. Using high throughput
      expression profiling, we have previously identified LIMD1 as a common marker
      associated with the oncogenic transcription factor IRF4 in EBV-related lymphomas
      and other hematological malignancies. In this study, we have identified potential
      conserved IRF4- and NFkappaB-binding motifs in the LIMD1 gene promoter, and both
      are demonstrated functional by promoter-reporter assays. We further show that
      LIMD1 is partially upregulated by EBV latent membrane protein 1 (LMP1) via IRF4
      and NFkappaB in EBV latency. As to its role in the setting of EBV latent
      infection, we show that LIMD1 interacts with TRAF6, a crucial mediator of LMP1
      signal transduction. Importantly, LIMD1 depletion impairs LMP1 signaling and
      functions, potentiates ionomycin-induced DNA damage and apoptosis, and inhibits
      p62-mediated selective autophagy. Taken together, these results show that LIMD1
      is upregulated in EBV latency and plays an oncogenic role rather than that of a
      tumor suppressor. Our findings have identified LIMD1 as a novel player in EBV
      latency and oncogenesis, and open a novel research avenue, in which LIMD1 and p62
      play crucial roles in linking DNA damage response (DDR), apoptosis, and autophagy
      and their potential interplay during viral oncogenesis.

PMID- 29464073
TI  - The possible existence of occult metastasis in patients with ovarian clear-cell
      carcinoma who underwent complete resection without any residual tumours.
AB  - The objective of this study was to estimate the frequency of possible occult
      metastasis through long-term survival analyses in patients with clear cell
      carcinoma (CCC) who had undergone complete resection. During the period of 1990
      2015, 799 patients with stage I-IV CCC were identified in the TOTSG database. Of
      these, a total of 528 patients without a residual tumor were enrolled in the
      study and classified into four groups: Group 1: FIGO stage IA-IB (N=104), Group
      2: FIGO stage IC1 (N=170), Group 3: FIGO stage IC2/IC3 (N=98), and Group 4: FIGO
      stage II-III (no residual tumor: N=156). Cumulative incidences of recurrence
      (CIR) and death (CID) were examined. The median age was 54, ranging from 29-87.
      The 5-year CIR / CID of each group were as follows: Group 1 (7.3% / 3.8%), Group
      2 (14.3% / 10.2%), Group 3 (37.7% / 18.4%), and Group 4 (46.5% / 33.8%),
      respectively {P<0.0001 (recurrence) / P<0.0001 (death)}. Furthermore, confining
      analysis to relapsed patients, 1-, 2-, and 3-year CID after recurrence were 41.5,
      60.9, and 73.9, respectively. Confining analyses to patients with sufficient
      information about adjuvant chemotherapy, the 5-year CIR / CID of stage IA-IC1
      patients with or without chemotherapy were as follows: recurrence {13.0% (yes) /
      9.6% (no)}, death {9.3% (yes) / 4.2% (no)}, respectively {P=0.947 (CIR) / P=0.224
      (CID)}. CCC patients staged greater than IC2/ IC3 show a marked risk of
      mortality, even after complete surgical resection.

PMID- 29464074
TI  - A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer
      cells.
AB  - Side effects of anti-cancer drugs are always challenging for effective cancer
      treatments. The polysaccharides extracted from Phellinus linteus (PLGL) have been
      widely used in treating cancers. However, the mechanism by which PLGL antagonizes
      cancerous growth has not been fully investigated. The current study demonstrated
      that human colon cancer HCT116 and HT29 cells became highly susceptible to cell
      death when being co-treated with PLGL and low dose of camptothecin11 (CPT11, a
      topoisomerase inhibitor-based drug), the efficacy of which was comparable as that
      generated by the high dose of CPT11. However, the co-treatment, unlike high doses
      of CPT11, was not cytotoxic to the control immortalized colon Caco-2 cells. The
      co-treatment caused high percentages of the colon cancer cells to accumulate in S
      phase of the cell cycle, which was also seen in the same cells received the high
      dose of CPT11 treatment. Chk1 was phosphorylated, and then rapidly degraded in
      the cancer cells treated with the high dose of CPT11 or co-treatment, but not in
      the cells treated with PLGL alone or low doses of CPT11. PLGL appeared enhancing
      CPT11 inhibitory effect on topoisomerase, and Chk1 degradatopm in the cancer
      cells. Furthermore, cyclin E (clnE) became unstable at the transcription level in
      co-treated or PLGL-treated colon cancer cells. The data suggested that PLGL
      functions in two ways to achieve its lethal synergy with CPT11 in colon cancer
      cells. Our findings are of potential significance as PLGL represents a promising
      medicine for overcoming the side effects of CPT11 and perhaps also for improving
      other CPTs-based regimens.

PMID- 29464075
TI  - Interleukin 8 activity influences the efficacy of adenoviral oncolytic
      immunotherapy in cancer patients.
AB  - After the landmark approval of T-VEC, oncolytic viruses are finding their way to
      the clinics. However, response rates have still room for improvement, and
      unfortunately there are currently no available markers to predict responses for
      oncolytic immunotherapy. Interleukin 8 (IL-8) production is upregulated in many
      cancers and it also connects to several pathways that have been shown to impair
      the efficacy of adenoviral immunotherapy. We studied the role of IL-8 in 103
      cancer patients treated with oncolytic adenoviruses. We found high baseline serum
      IL-8 concentration to be independently associated with poor prognosis (p<0.001).
      Further, normal baseline IL-8 was associated with improved prognostic potential
      of calculation of the neutrophil-to-lymphocyte ratio (p<0.001). Interestingly, a
      decrease in IL-8 concentration after treatment with oncolytic adenovirus
      predicted better overall survival (p<0.001) and higher response rate, although
      this difference was not significant (p=0.066). We studied the combination of
      adenovirus and IL-8 neutralizing antibody ex vivo in single cell suspensions and
      in co-cultures of tumor-associated CD15+ neutrophils and CD3+ tumor-infiltrating
      lymphocytes derived from fresh patient tumor samples. These results indicate a
      role for IL-8 as a biomarker in oncolytic virotherapy, but additionally provide a
      rationale for targeting IL-8 to improve treatment efficacy. In conclusion,
      curtailing the activity of IL-8 systemically or locally in the tumor
      microenvironment could improve anti-tumor immune responses resulting in enhanced
      efficacy of adenoviral immunotherapy of cancer.

PMID- 29464076
TI  - Quantitative radiomic profiling of glioblastoma represents transcriptomic
      expression.
AB  - Quantitative imaging biomarkers have increasingly emerged in the field of
      research utilizing available imaging modalities. We aimed to identify good
      surrogate radiomic features that can represent genetic changes of tumors, thereby
      establishing noninvasive means for predicting treatment outcome. From May 2012 to
      June 2014, we retrospectively identified 65 patients with treatment-naive
      glioblastoma with available clinical information from the Samsung Medical Center
      data registry. Preoperative MR imaging data were obtained for all 65 patients
      with primary glioblastoma. A total of 82 imaging features including first-order
      statistics, volume, and size features, were semi-automatically extracted from
      structural and physiologic images such as apparent diffusion coefficient and
      perfusion images. Using commercially available software, NordicICE, we performed
      quantitative imaging analysis and collected the dataset composed of
      radiophenotypic parameters. Unsupervised clustering methods revealed that the
      radiophenotypic dataset was composed of three clusters. Each cluster represented
      a distinct molecular classification of glioblastoma; classical type, proneural
      and neural types, and mesenchymal type. These clusters also reflected
      differential clinical outcomes. We found that extracted imaging signatures does
      not represent copy number variation and somatic mutation. Quantitative radiomic
      features provide a potential evidence to predict molecular phenotype and
      treatment outcome. Radiomic profiles represents transcriptomic phenotypes more
      well.

PMID- 29464077
TI  - Complement C4d-specific antibodies for the diagnosis of lung cancer.
AB  - Development of molecular markers that help to identify high-risk individuals or
      diagnose indeterminate pulmonary nodules could have a major impact on lung cancer
      clinical management. In this study, we evaluated the diagnostic potential of a
      newly-developed ELISA that specifically detects complement C4d. We measured this
      marker in five independent cohorts of plasma and bronchoalveolar lavage samples
      from lung cancer patients and controls. In case-control studies, the area under
      the ROC curve for the diagnosis of lung cancer was 0.82 (95%CI = 0.72-0.92) in
      plasma samples, and 0.80 (95%CI = 0.69 to 0.90) in bronchoalveolar lavage fluids.
      In a set of plasma samples from the MILD CT-screening trial, the assay was unable
      to discriminate between asymptomatic high-risk individuals with or without early
      stage lung cancer. On the contrary, in two independent cohorts of individuals
      with indeterminate pulmonary nodules, plasma samples from patients with lung
      cancer nodules presented higher levels of C4d than those from patients with
      benign nodules. Using a target population of patients with 8 to 30 mm nodules,
      the test identified likely benign lung nodules with 84% negative predictive value
      and 54% positive predictive value, at 89% specificity and 44% sensitivity. In
      conclusion, the specific determination of C4d may serve as an adjunct to current
      clinical practice in the diagnosis of indeterminate pulmonary nodules.

PMID- 29464078
TI  - Effects of a small molecule R-spondin-1 substitute RS-246204 on a mouse
      intestinal organoid culture.
AB  - Organoids, a multi-cellular and organ-like structure cultured in vitro, can be
      used in a variety of fields such as disease modeling, drug discovery, or cell
      therapy development. When organoids derived from Lgr5 stem cells are cultured ex
      vivo, recombinant R-spondin-1 protein should be added at a high concentration for
      the initiation and maintenance of the organoids. Because the addition of large
      amounts of R-spondin-1 greatly increases the cost of organoids, the organoids
      grown with R-spondin-1 are not practical for large-scale drug screening and for
      the development of therapeutic agents. In this study, we tried to find a R
      spondin-1 substitute compound that is able initiate small intestinal organoids
      without the use of the R-spondin-1 protein; thus, using organoid media that each
      included one compound from among an 8,364 compound library instead of R-spondin
      1, we observed whether organoids were established from the crypts of the small
      intestine. As a result, we found one compound that could promote the initial
      formation and growth of enteroids in the medium without R-spondin-1 and named it
      RS-246204. The enteroids grown with RS-246204 had a similar differentiation
      capacity as well as self-renewal capacity as the enteroids grown with R-spondin
      1. Furthermore, the RS-246204-derived enteroids could successfully produce the
      forskolin induced swelling and the organoid based epithelial to mesenchymal
      transition model. This compound could be used for developing a cost-efficient
      culturing method for intestinal organoids as well as for exploring Lgr5
      signaling, intestinal stem cell physiology and therapeutics for GI tract
      diseases.

PMID- 29464079
TI  - Differential tumor biological role of the tumor suppressor KAI1 and its splice
      variant in human breast cancer cells.
AB  - The tetraspanin and tumor suppressor KAI1 is downregulated or lost in many
      cancers which correlates with poor prognosis. KAI1 acts via physical/functional
      crosstalk with other membrane receptors. Also, a splice variant of KAI1 (KAI1-SP)
      has been identified indicative of poor prognosis. We here characterized
      differential effects of the two KAI1 variants on tumor biological events
      involving integrin (alphavbeta3) and/or epidermal growth factor receptor (EGF-R).
      In MDA-MB-231 and -435 breast cancer cells, differential effects were documented
      on the expression levels of the tumor biologically relevant integrin alphavbeta3
      which colocalized with KAI1-WT but not with KAI1-SP. Cellular motility was
      assessed by video image processing, including motion detection and vector
      analysis for the quantification and visualization of cell motion parameters. In
      MDA-MB-231 cells, KAI1-SP provoked a quicker wound gap closure and higher closure
      rates than KAI1-WT, also reflected by different velocities and average motion
      amplitudes of singular cells. KAI1-SP induced highest cell motion adjacent to the
      wound gap borders, whereas in MDA-MB-435 cells a comparable induction of both
      KAI1 variants was noticed. Moreover, while KAI1-WT reduced cell growth, KAI1-SP
      significantly increased it going along with a pronounced EGF-R upregulation. KAI1
      SP-induced cell migration and proliferation was accompanied by the activation of
      the focal adhesion and Src kinase. Our findings suggest that splicing of KAI1
      does not only abrogate its tumor suppressive functions, but even more, promotes
      tumor biological effects in favor of cancer progression and metastasis.

PMID- 29464080
TI  - Effects of interactions between common genetic variants and alcohol consumption
      on colorectal cancer risk.
AB  - Background: Genome-wide association studies (GWAS) have identified approximately
      40 common genetic loci associated with colorectal cancer risk. To investigate
      possible gene-environment interactions (GEIs) between GWAS-identified single
      nucleotide polymorphisms (SNPs) and alcohol consumption with respect to
      colorectal cancer, a hospital-based case-control study was conducted. Results:
      Higher levels of alcohol consumption as calculated based on a standardized
      definition of a drink (1 drink=12.5g of ethanol) were associated with increased
      risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers
      [>50g/day] compared to never drinkers; ptrend<0.01). SNP rs6687758 near the
      DUSP10 gene at 1q41 had a statistically significant interaction with alcohol
      consumption in analyses of standardized drinks (p=4.6*10-3), although this did
      not surpass the corrected threshold for multiple testing. When stratified by
      alcohol consumption levels, in an additive model the risk of colorectal cancer
      associated with the G allele of rs6687758 tended to increase among individuals in
      the heavier alcohol consumption strata. A statistically significant association
      between rs6687758 and colorectal cancer risk was observed among moderate alcohol
      drinkers who consumed between >12.5 and <=50g of alcohol per day (OR=1.46, 95%
      CI=1.01-2.11). Methods: A total of 2,109 subjects (703 colorectal cancer patients
      and 1,406 healthy controls) were recruited from the Korean National Cancer
      Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic
      regression model was used to evaluate associations of SNPs and alcohol
      consumption with colorectal cancer risk. We also tested GEIs between SNPs and
      alcohol consumption using a logistic model with multiplicative interaction terms.
      Conclusions: Our results suggest that SNP rs6687758 at 1q41 may interact with
      alcohol consumption in the etiology of colorectal cancer.

PMID- 29464081
TI  - DAPK and CIP2A are involved in GAS6/AXL-mediated Schwann cell proliferation in a
      rat model of bilateral cavernous nerve injury.
AB  - Purpose: Impotence is one of the major complications occurring in prostate cancer
      patients after radical prostectomy (RP). Self-repair of the injured nerve has
      been observed in animal models and in patients after RP. However, the downstream
      signalling is not well documented. Here, we found that the DAPK/CIP2A complex is
      involved in GAS6/AXL-related Schwann cell proliferation. Materials and Methods:
      The 3 groups were a sham group, a 14-day post-bilateral cavernous nerve injury
      (BCNI) group and a 28-day post-BCNI group. Erectile function was assessed and
      immunohistochemistry was performed. The rat Schwann cell RSC96 line was chosen
      for gene knockdown, cell viability, western blot, immunofluorescence and co
      immunoprecipitation assays. Results: The intracavernosal pressure was low on the
      14th day after BCNI and partially increased by the 28th day. GAS6 and p-AXL
      expression gradually increased in the cavernous nerve after BCNI. RSC96 cells
      incubated with a GAS6 ligand showed increased levels of p-ERK1/2 and p-AKT.
      Moreover, DAPK and CIP2A.p-AXL and p-DAPK and CIP2A complexes were identified by
      both immunoblotting and co-immunoprecipitation. Conclusion: The DAPK/CIP2A
      complex is involved in GAS6/AXL-related Schwann cell proliferation. CIP2A
      inhibits PP2A activity, which results in p-DAPK(S308) maintenance and promotes
      Schwann cell proliferation. CIP2A is a potential target for the treatment of
      nerve injury after RP.

PMID- 29464082
TI  - MYC-family protein overexpression and prominent nucleolar formation represent
      prognostic indicators and potential therapeutic targets for aggressive high-MKI
      neuroblastomas: a report from the children's oncology group.
AB  - Neuroblastomas with a high mitosis-karyorrhexis index (High-MKI) are often
      associated with MYCN amplification, MYCN protein overexpression and adverse
      clinical outcome. However, the prognostic effect of MYC-family protein expression
      on these neuroblastomas is less understood, especially when MYCN is not
      amplified. To address this, MYCN and MYC protein expression in High-MKI cases
      (120 MYCN amplified and 121 non-MYCN amplified) was examined by
      immunohistochemistry. The majority (101) of MYCN-amplified High-MKI tumors were
      MYCN(+), leaving one MYC(+), 2 both(+), and 16 both(-)/(+/-), whereas non-MYCN
      amplified cases appeared heterogeneous, including 7 MYCN(+), 36 MYC(+), 3
      both(+), and 75 both(-)/(+/-) tumors. These MYC-family proteins(+), or MYC-family
      driven tumors, were most likely to have prominent nucleolar (PN) formation
      (indicative of augmented rRNA synthesis). High-MKI neuroblastoma patients showed
      a poor survival irrespective of MYCN amplification. However, patients with MYC
      family driven High-MKI neuroblastomas had significantly lower survival than those
      with non-MYC-family driven tumors. MYCN(+), MYC-family protein(+), PN(+), and
      clinical stage independently predicted poor survival. Specific inhibition of
      hyperactive rRNA synthesis and protein translation was shown to be an effective
      way to suppress MYC/MYCN protein expression and neuroblastoma growth. Together,
      MYC-family protein overexpression and PN formation should be included in new
      neuroblastoma risk stratification and considered for potential therapeutic
      targets.

PMID- 29464083
TI  - TGF-beta2-induced EMT is dampened by inhibition of autophagy and TNF-alpha
      treatment.
AB  - Hepatocellular carcinoma (HCC) typically develops in a chronic inflammatory
      setting causal to release of a plethora of growth factors and cytokines. However,
      the molecular effect of these cytokines on HCC progression is poorly understood.
      In this study, we exposed HCC cells to TGF-beta2 (Transforming Growth Factor
      beta2), which resulted in a significant elevation of EMT (Epithelial to
      Mesenchymal Transition) like features. Molecular analysis of EMT markers showed
      an increase at both RNA and protein levels upon TGF-beta2 administration along
      with up-regulation of TGF-beta-induced Smad signaling. Induction of EMT was
      associated with a simultaneous increase in reactive oxygen species (ROS) and
      cytostasis of TGF-beta2-treated cells. Importantly, quenching of ROS resulted in
      a significant promotion of TGF-beta2-induced EMT. Furthermore, cells treated with
      TGF-beta2 also showed an enhanced autophagic flux. Interestingly, inhibition of
      autophagy by chloroquine-di-phosphate (CQDP) or siRNA-mediated ablation of ATG5
      drastically inhibited TGF-beta2-induced EMT. Autophagy inhibition significantly
      increased ROS levels promoting apoptosis. It was further observed that pro
      inflammatory cytokine like, TNF-alpha (Tumor Necrosis Factor-alpha) can
      antagonize TGF-beta2-induced response by down-regulating autophagy, increasing
      ROS levels and thus inhibiting EMT in HCC cells. This inhibitory effect of TNF
      alpha is serum-independent. Transcriptomic analysis through RNA sequencing was
      further performed which validated that TGF-beta2-induced autophagic genes are
      inhibited by TNF-alpha treatment suppressing EMT. Our study suggests that
      autophagy plays a pro-metastatic role facilitating EMT by regulating ROS levels
      in HCC cells and TNF-alpha can suppress EMT by inhibiting autophagy. We provide
      unique mechanistic insights into the role of TGF-beta2 in HCC cells, along with
      appropriate cues to effectively control the disease.

PMID- 29464084
TI  - Lysine-specific demethylase 1 inhibitors prevent teratoma development from human
      induced pluripotent stem cells.
AB  - Human induced pluripotent stem cells (hiPSCs) are creating great expectations for
      regenerative medicine. However, safety strategies must be put in place to guard
      against teratoma formation after transplantation of hiPSC-derived cells into
      patients. Recent studies indicate that epigenetic regulators act at the initial
      step of tumorigenesis. Using gain-of-function and loss-of-function approaches, we
      show here that the expression and function of lysine-specific demethylase 1
      (LSD1) are tightly regulated in hiPSCs, and their deregulation underlies the
      development of teratomas. Consistent with these results, we demonstrate that an
      LSD1 inhibitor, S2157, prevented teratoma formation from hiPSCs transplanted into
      immunodeficient mice. This novel action of LSD1 and the effects of its inhibition
      potentially allow for the development of new clinical applications and
      therapeutic strategies using hiPSCs.

PMID- 29464085
TI  - Intravesicular epidermal growth factor receptor subject to retrograde trafficking
      drives epidermal growth factor-dependent migration.
AB  - The Epidermal Growth Factor Receptor (EGFR) is frequently mutated and
      overexpressed in metastatic cancer. Although EGFR is a transmembrane tyrosine
      kinase localized to the basolateral membrane in normal epithelium, it is
      frequently found intracellularly localized in transformed cells. We have
      previously demonstrated the epithelial adaptor protein mucin 1 (MUC1) alters
      trafficking of EGFR, inhibiting its degradation and promoting its translocation
      to the nucleus, where it can directly modulate gene transcription. Here, we
      demonstrate that MUC1 promotes the retention of EGF-bound EGFR in Early Endosome
      Antigen1 (EEA1)-positive vesicles while preventing its trafficking to the
      lysosome. These events result in the accumulation of endosomal vesicles harboring
      active receptor throughout the cell and a reorganization of the actin
      cytoskeleton. EGF-dependent cell migration and filopodia formation is reliant
      upon this altered trafficking, and can be prevented by blocking retrograde
      trafficking. Together, these results indicate that intracellular EGFR may play an
      essential role in cancer metastasis and a potential mechanism for the failure of
      therapeutic antibodies in EGFR-driven metastatic breast cancer.

PMID- 29464086
TI  - SNP-array lesions in core binding factor acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) with t(8;21) and inv(16), together referred as core
      binding factor (CBF)-AML, are recognized as unique entities. Both rearrangements
      share a common pathophysiology, the disruption of the CBF, and a relatively good
      prognosis. Experiments have demonstrated that CBF rearrangements were
      insufficient to induce leukemia, implying the existence of cooperating events. To
      explore these aberrations, we performed single nucleotide polymorphism (SNP)
      array in a well-annotated cohort of 198 patients with CBF-AML. Excluding
      breakpoint-associated lesions, the most frequent events included loss of a sex
      chromosome (53%), deletions at 9q21 (12%) and 7q36 (9%) in patients with t(8;21)
      compared with trisomy 22 (13%), trisomy 8 (10%) and 7q36 deletions (12%) in
      patients with inv(16). SNP-array revealed novel recurrent genetic alterations
      likely to be involved in CBF-AML leukemogenesis. ZBTB7A mutations (20% of t(8;21)
      AML) were shown to be a target of copy-neutral losses of heterozygosity (CN-LOH)
      at chromosome 19p. FOXP1 focal deletions were identified in 5% of inv(16)-AML
      while sequence analysis revealed that 2% carried FOXP1 truncating mutations.
      Finally, CCDC26 disruption was found in both subtypes (4.5% of the whole cohort)
      and possibly highlighted a new lesion associated with aberrant tyrosine kinase
      signaling in this particular subtype of leukemia.

PMID- 29464087
TI  - 3D-Printed masks as a new approach for immobilization in radiotherapy - a study
      of positioning accuracy.
AB  - We developed a new approach to produce individual immobilization devices for the
      head based on MRI data and 3D printing technologies. The purpose of this study
      was to determine positioning accuracy with healthy volunteers. 3D MRI data of the
      head were acquired for 8 volunteers. In-house developed software processed the
      image data to generate a surface mesh model of the immobilization mask. After
      adding an interface for the couch, the fixation setup was materialized using a 3D
      printer with acrylonitrile butadiene styrene (ABS). Repeated MRI datasets (n=10)
      were acquired for all volunteers wearing their masks thus simulating a setup for
      multiple fractions. Using automatic image-to-image registration, displacements of
      the head were calculated relative to the first dataset (6 degrees of freedom).
      The production process has been described in detail. The absolute lateral (x),
      vertical (y) and longitudinal (z) translations ranged between -0.7 and 0.5 mm, 
      1.8 and 1.4 mm, and -1.6 and 2.4 mm, respectively. The absolute rotations for
      pitch (x), yaw (y) and roll (z) ranged between -0.9 and 0.8 degrees , -0.5 and
      1.1 degrees , and -0.6 and 0.8 degrees , respectively. The mean 3D displacement
      was 0.9 mm with a standard deviation (SD) of the systematic and random error of
      0.2 mm and 0.5 mm, respectively. In conclusion, an almost entirely automated
      production process of 3D printed immobilization masks for the head derived from
      MRI data was established. A high level of setup accuracy was demonstrated in a
      volunteer cohort. Future research will have to focus on workflow optimization and
      clinical evaluation.

PMID- 29464088
TI  - Deciphering microRNA targets in pancreatic cancer using miRComb R package.
AB  - MiRNAs are small non-coding RNAs that post-transcriptionally regulate gene
      expression. They play important roles in cancer but little is known about the
      specific functions that each miRNA exerts in each type of cancer. More knowledge
      about their specific targets is needed to better understand the complexity of
      molecular networks taking part in cancer. In this study we report the miRNA-mRNA
      interactome occurring in pancreatic cancer by using a bioinformatic approach
      called miRComb, which combines tissue expression data with miRNA-target
      prediction databases (TargetScan, miRSVR and miRDB). MiRNome and transcriptome of
      12 human pancreatic tissues (9 pancreatic ductal adenocarcinomas and 3 controls)
      were analyzed by next-generation sequencing and microarray, respectively.
      Analysis confirmed differential expression of both miRNAs and mRNAs in cancerous
      tissue versus control, and unveiled 17401 relevant miRNA-mRNA interactions likely
      to occur in pancreatic cancer. They were sorted according to the degree of
      negative correlation between miRNA and mRNA expression. Results highlighted the
      importance of miR-148a and miR-21 interactions among others. Two components of
      the Notch signaling pathway, ADAM17 and EP300, were confirmed as miR-148a targets
      in MiaPaca-2 pancreatic cancer cells overexpressing miR-148a. Moreover, a CRISPR
      Cas9 cellular model was generated to knock-out the expression of miR-21 in PANC-1
      cells. As expected, the expression of two miRComb miR-21 predicted targets, PDCD4
      and BTG2, was significantly upregulated in these cells in comparison to control
      PANC-1.

PMID- 29464089
TI  - Cysts mark the early stage of metastatic tumor development in non-small cell lung
      cancer.
AB  - Identifying metastatic tumor growth at an early stage has been one of the biggest
      challenges in the treatment of lung cancer. By genetic lineage tracing approach
      in a conditional model of Non-Small Cell Lung Cancer (NSCLC) in mice, we
      demonstrate that cystic lesions represent an early stage of metastatic invasion.
      We generated a mouse model for NSCLC which incorporated a heritable DsRed
      fluorescent tag driven by the ubiquitous CAG promoter in the alveolar type II
      cells of the lung. We found early cystic lesions in a secondary organ (liver)
      that lacked the expression of bona fide lung makers namely Scgb1a1 and surfactant
      protein C Sftpc and were DsRed positive hence identifying lung as their source of
      origin. This demonstrates the significant potential of alveolar type II cells in
      orchestrating the process of metastasis, rendering it as one of the target cell
      types of the lung of therapeutic importance in human NSCLC.

PMID- 29464090
TI  - T cell infiltration into Ewing sarcomas is associated with local expression of
      immune-inhibitory HLA-G.
AB  - Ewing sarcoma (EwS) is an aggressive mesenchymal cancer of bones or soft tissues.
      The mechanisms by which this cancer interacts with the host immune system to
      induce tolerance are not well understood. We hypothesized that the non-classical,
      immune-inhibitory HLA-molecule HLA-G contributes to immune escape of EwS. While
      HLA-Gpos suppressor T cells were not increased in the peripheral blood of EwS
      patients, HLA-G was locally expressed on the tumor cells and/or on infiltrating
      lymphocytes in 16 of 47 pretherapeutic tumor biopsies and in 4 of 12 relapse
      tumors. HLA-G expression was not associated with risk-related patient variables
      or response to standard chemotherapy, but with significantly increased numbers of
      tumor-infiltrating CD3+ T cells compared to HLA-Gneg EwS biopsies. In a mouse
      model, EwS xenografts after adoptive therapy with tumor antigen-specific CAR T
      cells strongly expressed HLA-G whereas untreated control tumors were HLA-Gneg.
      IFN-gamma stimulation of EwS cell lines in vitro induced expression of HLA-G
      protein. We conclude that EwS cells respond to tumor-infiltrating T cells by
      upregulation of HLA-G, a candidate mediator of local immune escape. Strategies
      that modulate HLA-G expression in the tumor microenvironment may enhance the
      efficacy of cellular immunotherapeutics in this cancer.

PMID- 29464091
TI  - Boolean analysis identifies CD38 as a biomarker of aggressive localized prostate
      cancer.
AB  - The introduction of serum Prostate Specific Antigen (PSA) testing nearly 30 years
      ago has been associated with a significant shift towards localized disease and
      decreased deaths due to prostate cancer. Recognition that PSA testing has caused
      over diagnosis and over treatment of prostate cancer has generated considerable
      controversy over its value, and has spurred efforts to identify prognostic
      biomarkers to distinguish patients who need treatment from those that can be
      observed. Recent studies show that cancer is heterogeneous and forms a hierarchy
      of tumor cell populations. We developed a method of identifying prostate cancer
      differentiation states related to androgen signaling using Boolean logic. Using
      gene expression data, we identified two markers, CD38 and ARG2, that group
      prostate cancer into three differentiation states. Cancers with CD38-, ARG2-
      expression patterns, corresponding to an undifferentiated state, had
      significantly lower 10-year recurrence-free survival compared to the most
      differentiated group (CD38+ARG2+). We carried out immunohistochemical (IHC)
      staining for these two markers in a single institution (Stanford; n = 234) and
      multi-institution (Canary; n = 1326) cohorts. IHC staining for CD38 and ARG2 in
      the Stanford cohort demonstrated that combined expression of CD38 and ARG2 was
      prognostic. In the Canary cohort, low CD38 protein expression by IHC was
      significantly associated with recurrence-free survival (RFS), seminal vesicle
      invasion (SVI), extra-capsular extension (ECE) in univariable analysis. In
      multivariable analysis, ARG2 and CD38 IHC staining results were not independently
      associated with RFS, overall survival, or disease-specific survival after
      adjusting for other factors including SVI, ECE, Gleason score, pre-operative PSA,
      and surgical margins.

PMID- 29464092
TI  - mTOR inhibition enhances efficacy of dasatinib in ABL-rearranged Ph-like B-ALL.
AB  - High-risk subtypes of B-cell acute lymphoblastic leukemia (B-ALL) include
      Philadelphia chromosome-positive (Ph+) B-ALL driven by the BCR-ABL1 oncogene and
      a more recently identified subtype known as BCR-ABL-like or Ph-like B-ALL. A
      hallmark of both Ph+ and Ph-like B-ALL is constitutive activation of tyrosine
      kinase signaling that is potentially targetable with tyrosine kinase inhibitors
      (TKIs). B-ALL cells also receive extracellular signals from the microenvironment
      that can maintain proliferation and survival following treatment with TKIs.
      Therefore, there is strong rationale for combining TKIs with other therapies
      targeting signal transduction pathways. Here we show that combinations of the ABL
      directed TKI dasatinib with mTOR kinase inhibitors (TOR-KIs) are more effective
      than TKI alone against patient-derived Ph-like B-ALL cells harboring
      rearrangements of ABL1 or ABL2. We also report the establishment of a new human
      Ph-like B-ALL cell line that is stromal cell-independent in vitro and can be used
      for xenograft experiments in vivo. These findings provide rationale for clinical
      testing of TKI plus TOR-KIs in children and adults with Ph-like B-ALL and a new
      experimental tool to test promising therapeutic strategies in this poor prognosis
      subtype of B-ALL.

PMID- 29464094
TI  - A meta-analysis on Omega-3 supplements in preventing recurrence of atrial
      fibrillation.
AB  - Previous studies had suggested that Omega-3 fatty acids have pleiotropic effects
      and favourable safety profile, which may potentially increase the efficacy of
      antiarrhythmic drugs in suppressing atrial arrhythmias through combination
      therapy. This meta-analysis aimed to determine the effectiveness of using Omega-3
      polyunsaturated fatty acids as a sole anti-arrhythmic agent or as an adjunct to
      existing pharmacological therapies in preventing atrial fibrillation recurrence.
      Randomized controlled trials published in English, from inception to December
      2016, were considered. We searched for published studies in the following
      electronic databases: Cochrane Central Register of Controlled Trials, PubMed,
      EMBASE, Medline, Scopus, and Cumulative Index to Nursing and Allied Health
      Literature. Pooled hazard ratio (HR) and corresponding 95% confidence intervals
      (CI) for time to first atrial fibrillation recurrence was analysed using a fixed
      effects model. Four RCTs with 1,268 participants were included in the review. Our
      results showed that Omega-3 polyunsaturated fatty acid therapy had no effect on
      preventing atrial fibrillation recurrence compared to control/placebo group (HR:
      1.13, 95% CI: 0.96 to 1.33, p = 0.14), with no significant heterogeneity found
      among those studies (Q value = 0.15, 9 = 0.99, I2 = 0%). Therefore, current
      evidence does not support treatment benefit of Omega-3 fatty acids in preventing
      atrial fibrillation recurrence among patients who have not been treated by any
      conventional reversion treatment, or who have only been treated with
      pharmacological therapy.

PMID- 29464093
TI  - Impact of LMP7 (rs2071543) gene polymorphism in increasing cancer risk: evidence
      from a meta-analysis and trial sequential analysis.
AB  - Genetic variant LMP7 (low molecular weight polypeptide 7) -145 C > A may
      influence the function of immune surveillance of an individual and lead to cancer
      development. Various studies have investigated the relevance of LMP7 -145 C > A
      gene polymorphism with cancer risk; but, their results are conflicting and
      inconsistent. To obtain a comprehensive conclusion, a meta-analysis was performed
      by including eight eligible published studies retrieved from PubMed (Medline),
      EMBASE and Google Scholar web search until December 2016. Individuals with AA
      genotype (AA vs CC: p = 0.001; OR = 2.602, 95% CI = 1.780 to 3.803) of LMP7 -145
      C > A were found to have 2 folds higher risk of cancer than those with CC
      genotype. The recessive genetic model (AA vs AC + CC) also indicated that
      individuals with AA genotype have 2 folds higher cancer risk than AC and CC
      genotypes (p = 0.001; OR = 2.216, 95% CI = 1.525 to 3.221). Also, significant
      increased cancer risk was observed in Asians but not in Caucasians. No
      publication bias was observed during the analysis. Trial sequential analysis also
      strengthened our current findings. These results suggest that genetic variant
      LMP7-145 C > A has significant role in increasing cancer risk in overall and
      Asian population, and could be useful as a prognostic marker for early cancer
      predisposition.

PMID- 29464095
TI  - An integrated analysis of hyponatremia in cancer patients receiving platinum
      based or nonplatinum-based chemotherapy in clinical trials (JCOG1405-A).
AB  - Background: Hyponatremia is a common electrolyte abnormality in cancer patients
      who receive chemotherapy. Among anticancer agents, platinum-based agents are
      reported to cause chemotherapy-induced hyponatremia. However, the actual
      incidence and risk factors remain unknown. Results: The reports of 29 trials were
      analyzed. The incidence of grade 3/4 hyponatremia was 11.9% in patients treated
      with platinum-based chemotherapy and 3.8% in those treated with nonplatinum-based
      regimens (P < 0.01). Univariable analysis revealed a high incidence of
      hyponatremia in patients receiving cisplatin, three-drug combination regimen, two
      drug combination regimen with amrubicin or irinotecan, or high-dose cisplatin
      (weekly equivalent cisplatin dose >=20 mg/m2), and in patients with small-cell
      lung cancer. Conclusion: This is the first report of the actual incidence and the
      potential risk factors of chemotherapy-induced hyponatremia. Careful monitoring
      of serum sodium level is needed when platinum-based chemotherapy is administered.
      Methods: This study included all clinical trials of systemic chemotherapies for
      solid cancers that were conducted by the Japan Clinical Oncology Group (JCOG)
      after January 2000 and of which the patient enrolment was completed by January
      2014. The latest reports of each trial were used for analysis. The incidence of
      chemotherapy-induced grade 3/4 hyponatremia and the potential risk factors were
      investigated with univariable analysis.

PMID- 29464096
TI  - A multicenter, retrospective analysis of elderly patients with acute myeloid
      leukemia who were treated with decitabine.
AB  - Decitabine is widely accepted as the treatment options for elderly acute myeloid
      leukemia (AML) patients. However, the efficacy has yet been assessed in Asian
      population. We retrospectively analyzed the outcomes of 80 Korean elderly AML
      patients who were treated with decitabine. The median age was 74 years (range, 64
      to 86 years) and 6 (7.5%), 48 (60.0%), and 25 (31.3%) patients were categorized
      to favorable, intermediate, and poor risk group, respectively. The median OS was
      10.2 months (95% CI 5.0-15.4). Given that decitabine treatment demonstrated
      improved clinical outcomes, it could be considered as one of the first-line
      treatment for Korean elderly AML patients.

PMID- 29464097
TI  - The association between hydroxychloroquine treatment and cardiovascular morbidity
      among rheumatoid arthritis patients.
AB  - Objectives: To examine the independent effect of hydroxychloroquine (HCQ)
      treatment on cardiovascular morbidity among RA patients. Materials and Methods: A
      retrospective cohort study of RA patients treated at Meir medical center between
      2003-2013 was conducted. Patients were divided into two groups, those who had
      been treated with HCQ during the course of their disease and those who had never
      received it. The two groups were compared for possible confounding factors. Study
      endpoints included arterial and venous thrombotic events. Results: A total of 514
      suitable RA patients were identified, 241 HCQ-treated and 273 non-treated
      patients. Of the HCQ-treated patients, 32 (13.3%) suffered from cardiovascular
      events compared to 104 (38.1%) of the non-treated group. HCQ treatment had a
      significant protective effect for all cardiovascular events examined (HR = 0.456
      CI 0.287 to 0.726) as well as arterial events alone (HR = 0.461 CI 0.274 to
      0.778). A dose of 400 mg HCQ per day demonstrated a protective effect for any
      cardiovascular event (HR = 0.432 CI 0.243 to 0.768), while the lower dose of 200
      mg per day showed no significant protective effect. Conclusions: The use of HCQ
      is independently associated with decreased risk for cardiovascular morbidity
      among RA patients, particularly with a higher dose of 400 mg per day. This newly
      demonstrated effect of HCQ should be considered in the overall management of RA.

PMID- 29464098
TI  - Forty five percent of the Israeli population were infected with the influenza B
      Victoria virus during the winter season 2015-16.
AB  - While infection with influenza A viruses has been extensively investigated,
      infections with influenza B viruses which are commonly categorized into the
      highly homologous Victoria and Yamagata lineages, are less studied, despite their
      considerable virulence. Here we used RT-PCR assays, hemagglutination inhibition
      assays and antibody titers to determine the levels of influenza B infection. We
      report of high influenza B Victoria virus prevalence in the 2015-16 winter season
      in Israel, affecting approximately half of the Israeli population. We further
      show that the Victoria B virus infected individuals of all ages and that it was
      present in the country throughout the entire winter season. The vaccine however
      included the inappropriate Yamagata virus. We propose that a quadrivalent
      vaccine, that includes both Yamagata and Victoria lineages, should be considered
      for future influenza vaccination.

PMID- 29464101
TI  - Pneumatocele during sorafenib therapy: first report of an unusual complication.
AB  - Sorafenib is a multi-kinase inhibitor and a vascular endothelial growth factor
      (VEGF) inhibitor approved to treat patients with advanced hepatocellular
      carcinoma, renal cell carcinoma and differentiated thyroid carcinoma. Its most
      common side effects are asthenia/fatigue, skin toxicity, diarrhea and arterial
      hypertension. Reported respiratory adverse reactions include dyspnea, cough,
      pleural effusion and hoarseness. The aim of this report is to describe for the
      first time the occurrence of pneumatocele in two patients treated with Sorafenib.
      Patients had no respiratory symptoms and alternative diagnoses were ruled out.
      Primary tumors were different (liver metastases from a pancreatic neuroendocrine
      tumor and hepatocellular carcinoma) but both patients had been treated with
      yttrium 90 radioembolization 9 and 17 months before starting on Sorafenib,
      respectively. No complications occurred and Sorafenib withdrawal was followed by
      radiologic improvement.

PMID- 29464100
TI  - Pancreatic cancer: disease dynamics, tumor biology and the role of the
      microenvironment.
AB  - Pancreatic cancer is known for its propensity to metastasize. Recent studies have
      challenged the commonly held belief that pancreatic cancer is a stepwise process,
      where tumor cells disseminate late in primary tumor development. Instead it has
      been suggested that pancreatic tumor cells may disseminate early and develop
      independently and in parallel to the primary tumor. Circulating tumor cells can
      be found in most patients with pancreatic cancer, even in those with localized
      stage. Also, recent phylogenetic analyses have revealed evidence for a branched
      evolution where metastatic lineages can develop early in tumor development. In
      this Review, we discuss current models of pancreatic cancer progression and the
      importance of the tumor microenvironment, in order to better understand the
      recalcitrant nature of this disease.

PMID- 29464099
TI  - Implications of KRAS mutations in acquired resistance to treatment in NSCLC.
AB  - Rationale: KRAS is the most common and, simultaneously, the most ambiguous
      oncogene implicated in human cancer. Despite KRAS mutations were identified in
      Non Small Cell Lung Cancers (NSCLCs) more than 20 years ago, selective and
      specific inhibitors aimed at directly abrogating KRAS activity are not yet
      available. Nevertheless, many therapeutic approaches have been developed
      potentially useful to treat NSCLC patients mutated for KRAS and refractory to
      both standard chemotherapy and targeted therapies.The focus of this review will
      be to provide an overview of the network related to the intricate molecular KRAS
      pathways, stressing on preclinical and clinical studies that investigate the
      predictive value of KRAS mutations in NSCLC patients. Materials and Methods: A
      bibliographic search of the Medline database was conducted for articles published
      in English, with the keywords KRAS, KRAS mutations in non-small cell lung cancer,
      KRAS and tumorigenesis, KRAS and TKIs, KRAS and chemotherapy, KRAS and monoclonal
      antibody, KRAS and immunotherapy, KRAS and drugs, KRAS and drug resistance.

PMID- 29464102
TI  - Development of an Estimation Instrument of Acoustic Lens Properties for Medical
      Ultrasound Transducers.
AB  - In medical ultrasound transducers, the transmission mode (pass-through) approach
      has been used to estimate the characteristics of the acoustic lens. However, it
      is difficult to measure the acoustic lens properties with high precision because
      of human, systemic, or mechanical measurement errors. In this paper, we propose a
      low-cost estimation instrument for acoustic lens properties connected with a
      customized database. In the instrument, three-axis and one-axis transmitting and
      material fixtures accurately align the transmitting and receiving transducers
      separately. Through the developed instrument, we obtained a precise standard
      deviation of the attenuation coefficient and velocity of the acoustic lens
      material of 0.05 dB/cm and 2.62 m/s, respectively. Additionally, the simultaneous
      alignment between the fixtures is controllable with developed programs, thus
      generating very accurate information of the acoustic lens about the testing
      ultrasound transducer. In our instrument, the database could support users in
      managing the result data efficiently. User programs developed using LabVIEW
      provide the capability to obtain precise values of the attenuation coefficient
      and velocity, which represent the fundamental material characteristics of the
      acoustic lens of the medical ultrasound transducers. The developed review program
      of the customized database can also search the acoustic lens information and
      store the experimental results.

PMID- 29464103
TI  - Dehydration is how you define it: comparison of 318 blood and urine athlete spot
      checks.
AB  - : Clinical medicine defines dehydration using blood markers that confirm
      hypertonicity (serum sodium concentration ([Na+])>145 mmol/L) and intracellular
      dehydration. Sports medicine equates dehydration with a concentrated urine as
      defined by any urine osmolality (UOsm) >=700 mOsmol/kgH2O or urine specific
      gravity (USG) >=1.020. Objective: To compare blood versus urine indices of
      dehydration in a cohort of athletes undergoing routine screenings. Methods: 318
      collegiate athletes (193 female) provided blood and urine samples and asked to
      rate how thirsty they were on a 10-point visual analogue scale. Serum was
      analysed for [Na+], while serum and UOsm were measured using an osmometer. USG
      was measured using a Chemstrip. Data were categorised into dehydrated versus
      hydrated groupings based on these UOsm and USG thresholds. Results: Using UOsm
      >=700 mOsmol/kgH2O to define dehydration, 55% of athletes were classified as
      dehydrated. Using any USG >=1.020 to define dehydration, 27% of these same
      athletes were classified as dehydrated. No athlete met the clinical definition
      for dehydration (hypertonicity; serum [Na+]>145 mmol/L). Normonatremia (serum
      [Na+] between 135 mmol/L and 145 mmol/L) was maintained in 99.7% of athletes
      despite wide variation in UOsm (110-1298 mOsmol/kgH2O). A significant correlation
      was confirmed between serum [Na+] versus UOsm (r=0.18; P<0.01), although urine
      concentration extremes did not reflect derangement in serum markers or thirst
      rating. Conclusion: Urine concentration thresholds classified 27%-55% of
      collegiate athletes as dehydrated, while no athlete was dehydrated according to
      blood [Na+] measurement. Practitioners should caution against using urine indices
      to diagnose or monitor dehydration, because urinary output is a response rather
      than a reflection of (tightly regulated) blood tonicity.

PMID- 29464104
TI  - Does ovulation affect performance in tennis players?
AB  - Background: Scientific data on the performance of collegiate female tennis
      players during the menstrual phases are scarce. Trial design: Double-blind,
      counter-balanced, crossover trials were conducted to examine whether tennis
      performance was affected during menstruation, with and without
      dehydroepiandrosterone sulfate (DHEA-S) supplementation. Methods: Ten Division 1
      collegiate tennis players (aged 18-22 years) were evenly assigned into placebo
      supplemented and DHEA-supplemented (25 mg/day) trials. Treatments were exchanged
      among the participants after a 28-day washout. Tennis serve performance was
      assessed on the first day of menstrual bleeding (day 0/28) and on days 7, 14 and
      21. Results: Mood state was unaltered during the menstrual cycles in both trials.
      The lowest tennis serve performance score (speed times accuracy) occurred on day
      14 (P=0.06 vs day 0; P=0.01 vs day 21) in both placebo and DHEA trials. Decreased
      performance on day 14 was explained by decreased accuracy (P=0.03 vs day 0/28;
      P=0.01 vs day 21), but not velocity itself. Isometric hip strength, but not
      quadriceps strength, was moderately lower on day 14 (P=0.08). Increasing plasma
      DHEA-S (by ~65%) during the DHEA-supplemented trial had no effects on mood state,
      sleep quality or tennis serve performance. Conclusion: We have shown that menses
      does not affect serve performance of collegiate tennis players. However, the
      observed decrement in the accuracy of serve speed near ovulation warrants further
      investigation.

PMID- 29464105
TI  - Osteochondral defects of the talus with a focus on platelet-rich plasma as a
      potential treatment option: a review.
AB  - Objective: To provide a review of osteochondral lesions of the talus, to discuss
      the evidence of the risks and benefits of platelet-rich plasma (PRP) as a viable
      treatment option, and to measure the efficacy of PRP using MRI evidence of
      cartilage regeneration, as well as scales that measure improvement in 'pain' and
      'functionality'. Eligibility criteria: Studies that use PRP in either
      conservative or intraoperative settings to treat osteochondral defects of the
      talus. Results: There are seven studies that compare hyaluronic acid or standard
      surgical options against PRP in treating osteochondral lesions of the talus. Five
      studies use PRP as supplemental treatment in intraoperative settings, while two
      studies use PRP conservatively as intra-articular injections. There were minimal
      adverse effects. Pain and functionality scores consistently improved in those who
      underwent PRP treatments over the course of 4 years. MRI showed significant but
      inconsistent results in chondral regeneration. Conclusion: PRP may show clinical
      benefit in those with osteochondral lesions of the talus in terms of pain and
      functionality, although chondral regeneration via MRI is inconsistent.
      Limitations include the small sample sizes in these seven studies, as well as no
      standardised formula for PRP preparation. Clinical relevance: To serve as an
      overview of the literature regarding PRP treatment for osteochondral lesions of
      the talus and how this modality may improve patient outcomes in pain,
      functionality and chondral regeneration. A case is reported to complement the
      subject review.

PMID- 29464106
TI  - Hospital-treated injuries from horse riding in Victoria, Australia: time to
      refocus on injury prevention?
AB  - Background: The most recent report on hospital-treated horse-riding injuries in
      Victoria was published 20 years ago. Since then, injury countermeasures and new
      technology have aimed to make horse riding safer for participants. This study
      provides an update of horse-riding injuries that required hospital treatment in
      Victoria and examines changes in injury patterns compared with the earlier study.
      Methods: Horse-riding injuries that required hospital treatment (hospital
      admission (HA) or emergency department (ED) presentations) were extracted from
      routinely collected data from public and private hospitals in Victoria from 2002
      2003 to 2015-2016. Injury incidence rates per 100 000 Victorian population per
      financial year and age-stratified and sex-stratified injury incidence rates are
      presented. Poisson regression was used to examine trends in injury rates over the
      study period. Results: ED presentation and HA rates were 31.1 and 6.6 per 100 000
      person-years, increasing by 28.8% and 47.6% from 2002 to 2016, respectively.
      Female riders (47.3 ED and 10.1 HA per 100 000 person-years) and those aged
      between 10 and 14 years (87.8 ED and 15.7 HA per 100 000 person-years) had the
      highest incidence rates. Fractures (ED 29.4%; HA 56.5%) and head injuries (ED
      15.4%; HA 18.9%) were the most common injuries. HA had a mean stay of 2.6+/-4.1
      days, and the mean cost per HA was $A5096+/-8345. Conclusion: Horse-riding
      injuries have remained similar in their pattern (eg, types of injuries) since
      last reported in Victoria. HA and ED incidence rates have increased over the last
      14 years. Refocusing on injury prevention countermeasures is recommended along
      with a clear plan for implementation and evaluation of their effectiveness in
      reducing injury.

PMID- 29464107
TI  - ESMO Leaders Generation Programme: an alumni insight.

PMID- 29464108
TI  - Abiraterone: moving up in line?

PMID- 29464109
TI  - Global cancer control: responding to the growing burden, rising costs and
      inequalities in access.
AB  - The cancer burden is rising globally, exerting significant strain on populations
      and health systems at all income levels. In May 2017, world governments made a
      commitment to further invest in cancer control as a public health priority,
      passing the World Health Assembly Resolution 70.12 on cancer prevention and
      control within an integrated approach. In this manuscript, the 2016 European
      Society for Medical Oncology Leadership Generation Programme participants propose
      a strategic framework that is in line with the 2017 WHO Cancer Resolution and
      consistent with the principle of universal health coverage, which ensures access
      to optimal cancer care for all people because health is a basic human right. The
      time for action is now to reduce barriers and provide the highest possible
      quality cancer care to everyone regardless of circumstance, precondition or
      geographic location. The national actions and the policy recommendations in this
      paper set forth the vision of its authors for the future of global cancer control
      at the national level, where the WHO Cancer Resolution must be implemented if we
      are to reduce the cancer burden, avoid unnecessary suffering and save as many
      lives as possible.

PMID- 29464110
TI  - Phase I study of the investigational oral mTORC1/2 inhibitor sapanisertib (TAK
      228): tolerability and food effects of a milled formulation in patients with
      advanced solid tumours.
AB  - Background: Sapanisertib (TAK-228) is an investigational, orally available,
      potent and highly selective mTORC1/2 inhibitor demonstrating promise in numerous
      malignancies. This phase I study (NCT02412722) evaluated the safety,
      tolerability, pharmacokinetics and antitumour activity of single-agent TAK-228
      (milled capsules), administered daily (QD) or weekly (QW) and in combination with
      paclitaxel in patients with advanced solid tumours. Pharmacokinetic comparisons
      of milled versus unmilled TAK-228 and the impact of food were also investigated.
      Methods: Patients were enrolled to receive: TAK-228 QD, TAK-228 3 days/week plus
      paclitaxel 80 mg/m2 days 1, 8, 15 (TAK-228+P) or TAK-228 QW (all 28-day cycles);
      starting TAK-228 doses were 4, 6 and 20 mg, respectively. Results: Sixty-one
      adults were enrolled. Maximum tolerated doses for milled TAK-228 were 3 mg (TAK
      228 QD), 6 mg (TAK-228+P) and 30 mg (TAK-228 QW). Most patients reported >=1
      adverse event (AE); there were no meaningful differences in drug-related AEs
      across regimens or doses. Three on-study deaths occurred, all considered
      unrelated to study drugs. TAK-228 pharmacokinetics did not differ between
      unmilled/milled capsules or with/without paclitaxel. However, TAK-228 Cmax
      decreased by ~40% in fed versus fasted patients. Objective response rates were
      12% (TAK-228 QD), 18% (TAK-228+P) and 0% (TAK-228 QW). One patient receiving TAK
      228+P had a complete response; three patients receiving TAK-228+P and two
      patients receiving TAK-228 QD had partial responses. Conclusions: Milled TAK-228
      was well tolerated with signs of antitumour activity; administration did not
      reduce overall exposure (area under the plasma concentration-time curve) but
      reduced Cmax, which is expected when dosed in the fed state. These promising
      findings warrant further investigation. Trial registration number: NCT02412722.

PMID- 29464111
TI  - Circulating cell-free plasma tumour DNA shows a higher incidence of EGFR
      mutations in patients with extrathoracic disease progression.

PMID- 29464113
TI  - In the literature: February 2018.

PMID- 29464112
TI  - Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against
      the epidermal growth factor receptor, in patients with advanced carcinomas.
AB  - Background: Changes in glycosylation of the constant domain (Fc) of monoclonal
      antibodies (mAbs) enhance antibody-dependent cell-mediated cytotoxicity
      independently of downstream effects following receptor blockade by the antibody,
      thus extending their indication. We investigated the safety, pharmacokinetics,
      pharmacodynamics and antitumour activity of tomuzotuximab, an IgG1
      glycoengineered mAb against the epidermal growth factor receptor with enhanced
      tumour cytotoxicity in a phase I dose-escalation study (NTC01222637). Patients
      and methods: Forty-one patients with advanced solid tumours refractory to
      standard therapies received tomuzotuximab weekly (12-1370 mg) or two-weekly (990
      mg) on a three-plus-three dose escalation design. Results: A maximum tolerated
      dose was not reached. The most frequent treatment-related adverse events were
      infusion-related reactions in 31 (76%) patients (grade 3, 12%), mainly confined
      to the first dose, and skin toxicities (grade 1 or 2) in 30 (73%) patients.
      Hypomagnesaemia was observed in 9 out of 23 evaluable patients (39%). Similar to
      cetuximab, tomuzotuximab concentrations increased proportionally to dose from
      doses>=480 mg with a median terminal half life (t1/2) of 82 hours, range 55-113
      hours. Antitumour activity included one complete response ongoing since more than
      4.5 years in a patient with non-small-cell lung cancer and one partial response
      lasting 353 days in a patient with colorectal cancer. Twelve patients achieved
      stable disease (median, 166 days, range, 71-414 days) and two patients had
      prolonged control (>1 year) of their non-measurable disease. Conclusion:
      Tomuzotuximab was safe and showed promising antitumour activity in heavily
      pretreated patients with advanced metastatic disease. A phase IIb trial of
      chemotherapy and weekly tomuzotuximab or cetuximab followed with maintenance
      therapy with the corresponding mAb in patients with recurrent or metastatic head
      and neck squamous cell carcinoma is ongoing.

PMID- 29464114
TI  - Primary Outcomes of Accelerated Epithelium-Off Corneal Cross-Linking in
      Progressive Keratoconus in Children: A 1-Year Prospective Study.
AB  - Purpose: To evaluate corneal transparency following accelerated collagen cross
      linking (ACXL) in pediatric keratoconus. Design: A prospective interventional
      case series. Methods: This study included 47 eyes (25 patients), aged 9-14 years,
      with documented progressive keratoconus. After applying 0.1% riboflavin drops,
      ACXL was performed. Assessment included corrected distance visual acuity (CDVA),
      uncorrected visual acuity (UCVA), corneal haze, and corneal densitometry in
      grayscale units (GSU). Result: The mean baseline and corneal densitometry peaked
      at 3 months post-ACXL while central and posterior densitometry showed a
      statistically significant increase (P < 0.05) and peaked at 8 months
      postoperatively. By 12 months, densitometry in all corneal layers (P >= 0.99) and
      concentric zones (P >= 0.97) reached near baseline values. Slit-lamp graded haze
      peaked at 1 month to 1.82 +/- 0.65 (P < 0.05) and declined to near baseline at 12
      months (0.39 +/- 0.58). There was a statistically significant increase in the
      mean UCVA and CDVA at 12 months. Conclusion: Total and anterior corneal
      densitometry peaked after 3 months, while central and posterior densitometry
      peaked after 8 months. Maximum haze was at 1 month post-ACXL. All corneal layers,
      concentric zone densitometry and haze reached near baseline values after 1 year.
      Scheimpflug densitometry showed weak correlation with CDVA over the 12-month
      follow-up period (r = -0.193).

PMID- 29464115
TI  - Ocular Biometry in Primary Angle-Closure Glaucoma Associated with Retinitis
      Pigmentosa.
AB  - Background: Retinitis pigmentosa (RP) comprises a group of inherited disorders in
      which patients typically lose night vision in adolescence and then lose
      peripheral vision in young adulthood before eventually losing central vision
      later in life. A retrospective case-control study was performed to evaluate
      differences in ocular biometric parameters in primary angle-closure glaucoma
      (PACG) patients with and without concomitant RP to determine whether a
      relationship exists between PACG and RP. Methods: We used ultrasound
      biomicroscopy (UBM) to measure anterior chamber depth (ACD). A-scan biometry was
      carried out to measure lens thickness (LT) and axial length (AL). Propensity
      score matching and mixed linear regression model analysis were conducted. 23
      patients with chronic primary angle-closure glaucoma (CPACG) associated with RP,
      21 patients with acute primary angle-closure glaucoma (APACG) associated with RP,
      270 patients with CPACG, and 269 patients with APACG were recruited for this
      study. Results: There were no significant differences on ACDs, ALs, and relative
      lens position (RLP) (P > 0.05) between patients with PACG associated with RP and
      patients with PACG; however, patients with APACG associated with RP had a
      significantly greater LT than patients with APACG (P < 0.05). Conclusion:
      Patients with PACG associated with RP had the same biometric parameter
      characteristic as the patients with CPACG and APACG. This may suggest that RP is
      a coincidental relationship with angle-closure glaucoma.

PMID- 29464116
TI  - Putative HIV and SIV G-Quadruplex Sequences in Coding and Noncoding Regions Can
      Form G-Quadruplexes.
AB  - The HIV virus is one of the most studied viruses in the world. This is especially
      true in terms of gene sequencing, and to date more than 9 thousand genomic
      sequences of HIV isolates have been sequenced and analyzed. In this study, a
      series of DNA sequences, which have the potential to form G-quadruplex
      structures, is analyzed. Several such sequences were found in various coding and
      noncoding virus domains, including the U3 LTR, tat, rev, env, and vpx regions.
      Interestingly, a homological sequence to the already well-known HIV integrase
      aptamer was identified in the minus-strand. The sequences derived from original
      isolates were analyzed using standard spectral and electrophoretic methods. In
      addition, a recently developed methodology is applied which uses induced circular
      dichroism spectral profiles of G-quadruplex-ligand (Thiazole Orange) complexes to
      determine if G-rich sequences can adopt G-quadruplex structure. Targeting the G
      quadruplexes or peptide domains corresponding to the G-rich coding sequence in
      HIV offers researchers attractive therapeutic targets which would be of
      particular use in the development of novel antiviral therapies. The analysis of G
      rich regions can provide researchers with a path to find specific targets which
      could be of interest for specific types of virus.

PMID- 29464117
TI  - Metabolomic Insights into the Nutritional Status of Adults and Adolescents with
      Phenylketonuria Consuming a Low-Phenylalanine Diet in Combination with Amino Acid
      and Glycomacropeptide Medical Foods.
AB  - Background: Nutrient status in phenylketonuria (PKU) requires surveillance due to
      the restrictive low-Phe diet in combination with amino acid medical foods (AA-MF)
      or glycomacropeptide medical foods (GMP-MF). Micronutrient profiles of medical
      foods are diverse, and optimal micronutrient supplementation in PKU has not been
      established. Methods: In a crossover design, 30 participants with PKU were
      randomized to consume AA-MF and GlytactinTM GMP-MF in combination with a low-Phe
      diet for 3 weeks each. Fasting venipunctures, medical food logs, and 3-day food
      records were obtained. Metabolomic analyses were completed in plasma and urine by
      Metabolon, Inc. Results: The low-Phe diets in combination with AA-MF and GMP-MF
      were generally adequate based on Dietary Reference Intakes, clinical measures,
      and metabolomics. Without micronutrient supplementation of medical foods, >70% of
      participants would have inadequate intakes for 11 micronutrients. Despite
      micronutrient supplementation of medical foods, inadequate intakes of potassium
      in 93% of participants and choline in >40% and excessive intakes of sodium in
      >63% of participants and folic acid in >27% were observed. Sugar intake was
      excessive and provided 27% of energy. Conclusions: Nutrient status was similar
      with AA-MF and Glytactin GMP-MF. More research related to micronutrient
      supplementation of medical foods for the management of PKU is needed.

PMID- 29464118
TI  - Health Behaviour among Nurses Working in Public Hospitals in Kakamega County,
      Kenya.
AB  - Health behaviour refers to actions undertaken by a person who perceives self to
      be ill for the purpose of finding an appropriate remedy. Nurses as gate keepers
      of health are expected to seek formal treatment when they are taken ill because
      this is what they teach their patients. Nurses' working conditions all over the
      world are described as squalid with long working hours and workload. This
      scenario predisposes them to occupational health hazards and at the same time
      denies them time for self-care. Although nurses are knowledgeable about disease
      and its treatment and have access to health care, they engage in self-treatment
      in contrast to what they teach patients. Health behaviour among nurses in
      Kakamega County was investigated using a cross-sectional design. Data was
      collected using self-administered questionnaires and subjected to bivariate and
      logistic regression analyses. The study found that health behaviour of nurses in
      Kakamega County is below expectation, as 33% (n = 61) engaged in voluntary
      screening services. Further, 34.8% (n = 65) said that their health would improve
      if they engaged in health promotion activities. The study recommends empowering
      nurses to engage in positive health behaviour through education. The county
      should also provide affordable screening services to its nurses.

PMID- 29464119
TI  - Instrumental Mechanoreceptoric Palpation in Gastrointestinal Surgery.
AB  - Background and Aims: Small gastric or colorectal tumours can be visually
      undetectable during laparoscopic surgeries, and available methods still do not
      provide a 100% localisation rate. Thus, new methods for further improvements in
      tumour localisation are highly desirable. In this study, we evaluated the usage
      of the Medical Tactile Endosurgical Complex (MTEC) in gastrointestinal surgery
      for localisation of tumours. The MTEC provides the possibility of instrumental
      mechanoreceptoric palpation, which serves as an analogue of conventional manual
      palpation. Methods: Ninety-six elective surgeries were performed, including 48
      open surgeries, 43 laparoscopies, and 5 robot-assisted surgeries. The 20 mm
      version of the MTEC tactile mechanoreceptor was used in open surgeries, and the
      10 mm version in laparoscopic and robot-assisted surgeries. Results: The mean
      time of instrumental mechanoreceptoric palpation was 3 minutes 12 seconds for
      open surgeries, which constituted the early stage of the learning curve, and 3
      minutes 34 seconds for laparoscopic surgeries. No side effects or postoperative
      complications related to instrumental mechanoreceptoric palpation were observed,
      and this procedure provided data sufficient for tumour localisation in more than
      95% of cases. Conclusion: Instrumental mechanoreceptoric palpation performed
      using MTEC is a simple, safe, and reliable method for tumour localisation in
      gastrointestinal laparoscopic surgery.

PMID- 29464120
TI  - Pain and Stress Response during Intravenous Access in Children with Congenital
      Adrenal Hyperplasia: Effects of EMLA and Nitrous Oxide Treatment.
AB  - Background: Congenital adrenal hyperplasia (CAH) is an endocrine condition that
      requires regularly blood samples for optimal treatment. The management of CAH in
      children is complex when intravenous access is one of the most stressful
      procedures for children. The purpose of this pilot study was to investigate the
      effects of nitrous oxide inhalation (N2O) in combination with cutaneous
      application of local anesthetics (EMLA) for improving intravenous access in
      children with CAH. Method: Ten children (7-14 years) were studied. The children
      received two intravenous procedures: one with EMLA and one with EMLA + N2O. The
      order of priority was randomized. The outcomes were the children's pain
      experience (0-10) and an evaluation of satisfaction (1-5) after the procedure.
      Heart rate, blood pressure, saturation, and analyses of 17-hydroxyprogesterone
      (17-OHP), norepinephrine, and glucose were analyzed. Results: Higher pain scores,
      heart rate, and glucose levels were reported after EMLA, compared to EMLA + N2O,
      but 17-OHP levels remained unchanged. The children's satisfaction with the
      intravenous procedure was more positive for EMLA + N2O. Conclusions: EMLA + N2O
      offers the possibility of improving the intravenous procedure for anxious
      children with CAH. Although the quality of care was better with N2O treatment, it
      was not possible to demonstrate that this is a prerequisite for valid 17-OHP
      measurements.

PMID- 29464121
TI  - Interaction Effects of Season of Birth and Cytokine Genes on Schizotypal Traits
      in the General Population.
AB  - Literature suggests that the effect of winter birth on vulnerability to
      schizophrenia might be mediated by increased expression of proinflammatory
      cytokines due to prenatal infection and its inadequate regulation by anti
      inflammatory factors. As the response of the immune system depends on genotype,
      this study assessed the interaction effects of cytokine genes and season of birth
      (SOB) on schizotypy measured with the Schizotypal Personality Questionnaire (SPQ
      74). We searched for associations of IL1B rs16944, IL4 rs2243250, and IL-1RN VNTR
      polymorphisms, SOB, and their interactions with the SPQ-74 total score in a
      sample of 278 healthy individuals. A significant effect of the IL4 X SOB
      interaction was found, p = 0.007 and eta2 = 0.028. We confirmed this effect using
      an extended sample of 373 individuals. Homozygotes CC born in winter showed the
      highest SPQ total score and differed significantly from winter-born T allele
      carriers, p = 0.049. This difference was demonstrated for cognitive-perceptual
      and disorganized but not interpersonal dimensions. The findings are consistent
      with the hypothesis that the cytokine genes by SOB interaction can influence
      variability of schizotypal traits in the general population. The IL4 T allele
      appeared to have a protective effect against the development of positive and
      disorganized schizotypal traits in winter-born individuals.

PMID- 29464122
TI  - The Use of BEREP4 Immunohistochemistry Staining for Detection of Basal Cell
      Carcinoma.
AB  - Basal Cell Carcinoma (BCC) is the most common type of malignant cancer found in
      the world today with a 3-10% increase in incidence each year. The American Cancer
      Society reported that 8 out of 10 patients with skin cancer are suffering from
      BCC with over 2 million new cases each year. BCC needs to be detected at the
      early stages to prevent local destruction causing disabilities to patients and
      increasing treatment costs. Furthermore, BCC patients who have undergone surgery
      are still at risk for recurrence, especially when the surgery performed fails to
      remove all the BCC cells, even when conventional histopathological testing after
      surgery has reported a surgically free margin. This review aims to evaluate
      studies on the use of BerEP4 immunohistochemistry staining on pathological
      sections of various types of BCC as well as its shortfalls. BerEP4 is a
      monoclonal antibody which detects specific epithelial-glycoprotein-adhesion
      molecules (EpCAM) found on BCC cells. Various studies have shown that BerEP4 has
      a high sensitivity and specificity in detecting only BCC cells. The use of BerEP4
      immunohistochemistry testing for the routine examination of cases of BCC is
      expected to be able to increase and improve early diagnosis as well as prevent
      recurrence after surgery.

PMID- 29464124
TI  - Epstein-Barr Virus as a Promising Immunotherapeutic Target for Nasopharyngeal
      Carcinoma Treatment.
AB  - Epstein-Barr virus (EBV) is a pathogen that infects more than 90% of global human
      population. EBV primarily targets B-lymphocytes and epithelial cells while some
      of them infect monocyte/macrophage, T-lymphocytes, and dendritic cells (DCs). EBV
      infection does not cause death by itself but the infection has been persistently
      associated with certain type of cancers such as nasopharyngeal carcinoma (NPC),
      Burkitt's lymphoma (BL), and Hodgkin's lymphoma (HL). Recent findings have shown
      promise on targeting EBV proteins for cancer therapy by immunotherapeutic
      approach. Some studies have also shown the success of adopting EBV-based
      therapeutic vaccines for the prevention of EBV-associated cancer particularly on
      NPC. In-depth investigations are in progress to refine the current therapeutic
      and vaccination strategies. In present review, we discuss the highly potential
      EBV targets for NPC immunotherapy and therapeutic vaccine development as well as
      addressing the underlying challenges in the process of bringing the therapy and
      vaccination from the bench to bedside.

PMID- 29464123
TI  - Targeted Therapeutic Nanoparticles: An Immense Promise to Fight against Cancer.
AB  - In nanomedicine, targeted therapeutic nanoparticle (NP) is a virtual outcome of
      nanotechnology taking the advantage of cancer propagation pattern. Tying up all
      elements such as therapeutic or imaging agent, targeting ligand, and cross
      linking agent with the NPs is the key concept to deliver the payload selectively
      where it intends to reach. The microenvironment of tumor tissues in lymphatic
      vessels can also help targeted NPs to achieve their anticipated accumulation
      depending on the formulation objectives. This review accumulates the application
      of poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) based NP
      systems, with a specific perspective in cancer. Nowadays, PLGA, PEG, or their
      combinations are the mostly used polymers to serve the purpose of targeted
      therapeutic NPs. Their unique physicochemical properties along with their
      biological activities are also discussed. Depending on the biological effects
      from parameters associated with existing NPs, several advantages and limitations
      have been explored in teaming up all the essential facts to give birth to
      targeted therapeutic NPs. Therefore, the current article will provide a
      comprehensive review of various approaches to fabricate a targeted system to
      achieve appropriate physicochemical properties. Based on such findings,
      researchers can realize the benefits and challenges for the next generation of
      delivery systems.

PMID- 29464126
TI  - Thrombosis in the Surgically Corrected Anomalous Right Coronary Artery after
      Reimplantation in Aorta.
AB  - A 32-year-old African American female presented with dyspnea, and after several
      cardiac diagnostic tests, the diagnosis of an anomalous origin of the RCA from
      the pulmonary trunk was established by multislice coronary CT angiography. She
      underwent surgical correction with reimplantation of the RCA, from the pulmonary
      artery to the aortic root. However, 10 days after surgery, she developed frequent
      episodes of chest pain, and repeat coronary CTA showed a partially occlusive
      thrombus in the surgically reimplanted RCA. Anticoagulation with warfarin
      resulted in complete resolution of the patient's symptoms.

PMID- 29464125
TI  - Botanicals as Modulators of Neuroplasticity: Focus on BDNF.
AB  - The involvement of brain-derived neurotrophic factor (BDNF) in different central
      nervous system (CNS) diseases suggests that this neurotrophin may represent an
      interesting and reliable therapeutic target. Accordingly, the search for new
      compounds, also from natural sources, able to modulate BDNF has been increasingly
      explored. The present review considers the literature on the effects of
      botanicals on BDNF. Botanicals considered were Bacopa monnieri (L.) Pennell,
      Coffea arabica L., Crocus sativus L., Eleutherococcus senticosus Maxim., Camellia
      sinensis (L.) Kuntze (green tea), Ginkgo biloba L., Hypericum perforatum L., Olea
      europaea L. (olive oil), Panax ginseng C.A. Meyer, Rhodiola rosea L., Salvia
      miltiorrhiza Bunge, Vitis vinifera L., Withania somnifera (L.) Dunal, and Perilla
      frutescens (L.) Britton. The effect of the active principles responsible for the
      efficacy of the extracts is reviewed and discussed as well. The high number of
      articles published (more than one hundred manuscripts for 14 botanicals) supports
      the growing interest in the use of natural products as BDNF modulators. The
      studies reported strengthen the hypothesis that botanicals may be considered
      useful modulators of BDNF in CNS diseases, without high side effects. Further
      clinical studies are mandatory to confirm botanicals as preventive agents or as
      useful adjuvant to the pharmacological treatment.

PMID- 29464127
TI  - Use of High-Flow Nasal Cannula Oxygen Therapy in a Pregnant Woman with
      Dermatomyositis-Related Interstitial Pneumonia.
AB  - A 33-year-old pregnant woman was referred to our hospital with respiratory
      distress at 30 weeks of gestation. Chest computed tomography (CT) scans revealed
      pulmonary infiltrates along the bronchovascular bundles and ground-glass
      opacities in both lungs. Despite immediate treatment with steroid pulse therapy
      for suspected interstitial pneumonia, the patient's condition worsened.
      Respiratory distress was slightly alleviated after the initiation of high-flow
      nasal cannula (HFNC) oxygen therapy (40 L/min, FiO2 40%). We suspected clinically
      amyopathic dermatomyositis (CADM) complicating rapidly progressive refractory
      interstitial pneumonia. In order to save the life of the patient, the use of
      combination therapy with immunosuppressants was necessary. The patient underwent
      emergency cesarean section and was immediately treated with immunosuppressants
      while continuing HFNC oxygen therapy. The neonate was treated in the neonatal
      intensive care unit. The patient's condition improved after 7 days of
      hospitalization; by this time, she was positive for myositis-specific
      autoantibodies and was diagnosed with interstitial pneumonia preceding
      dermatomyositis. This condition can be potentially fatal within a few months of
      onset and therefore requires early combination immunosuppressive therapy. This
      case demonstrates the usefulness of HFNC oxygen therapy for respiratory
      management as it negates the need for intubation and allows for various
      treatments to be quickly performed.

PMID- 29464128
TI  - Perianal Comedones: A Rare Incidental Finding.
AB  - Comedones occur when an overproliferation of keratinocytes blocks sebum secretion
      in a pilosebaceous duct. Comedones have multiple possible etiologies and
      contributing factors. While comedones are common to acne, they are also seen in
      occupational exposures and are associated with certain syndromes. We describe a
      particularly rare case of comedones at the perianus that is not associated with
      any known exposure or disease and is a rare incidental finding.

PMID- 29464129
TI  - A Peculiar Case of Invasive Streptococcus pneumoniae.
AB  - Patients commonly present to the emergency department with acute respiratory
      distress; however, the differentials are broad and at times difficult to
      distinguish. We describe a case of severe community-acquired pneumonia (CAP)
      secondary to invasive Streptococcus pneumoniae. The patient was intubated within
      3 h of presentation and suffered multiorgan failure within 72 h of intensive care
      unit (ICU) admission. This case is a stark illustration of how the most common
      bacteria associated with CAP can be fatal and highlights the associated markers
      of severity. It also outlines other potential complications including a very rare
      phenomenon of cardiomyopathy with myocarditis associated with S. pneumoniae
      bacteraemia.

PMID- 29464130
TI  - Osteoid Osteoma of the Trapezium: Case Report of an Unusual Tumor Location
      Presenting a Diagnostic Challenge.
AB  - Osteoid osteoma is a benign bone tumor, which represents approximately 10% of all
      benign bone tumors. When localized to the carpus, osteoid osteomas are most often
      seen in the scaphoid and capitate. Rarely, these tumors can also be observed in
      the trapezium. Given the infrequency with which osteomas are located in the
      trapezium and often nonspecific presenting symptoms, diagnosis of this tumor can
      be challenging and requires a high index of suspicion.

PMID- 29464131
TI  - Nutritional Aspects of Bone Health and Fracture Healing.
AB  - Introduction: Fractures are quite common, especially among the elderly. However,
      they can increase in prevalence in younger ages too if the bone health is not
      good. This may happen as a result of bad nutrition. Methods: A customized,
      retrospective review of available literature was performed using the following
      keywords: bone health, nutrition, and fractures. Results: Insufficient intake of
      certain vitamins, particularly A and D, and other nutrients, such as calcium, may
      affect bone health or even the time and degree of bone healing in case of
      fracture. The importance of different nutrients, both dietary and found in food
      supplements, is discussed concerning bone health and fracture healing.
      Conclusion: A healthy diet with adequate amounts of both macro- and
      micronutrients is essential, for both decreasing fracture risk and enhancing the
      healing process after fracture.

PMID- 29464132
TI  - Crowd-sourced Ontology for Photoleukocoria: Identifying Common Internet Search
      Terms for a Potentially Important Pediatric Ophthalmic Sign.
AB  - Purpose: Leukocoria is the most common presenting sign for pediatric eye disease
      including retinoblastoma and cataract, with worse outcomes if diagnosis is
      delayed. We investigated whether individuals could identify leukocoria in
      photographs (photoleukocoria) and examined their subsequent Internet search
      behavior. Methods: Using a web-based questionnaire, in this cross-sectional study
      we invited adults aged over 18 years to view two photographs of a child with
      photoleukocoria, and then search the Internet to determine a possible diagnosis
      and action plan. The most commonly used search terms and websites accessed were
      recorded. Results: The questionnaire was completed by 1639 individuals. Facebook
      advertisement was the most effective recruitment strategy. The mean age of all
      respondents was 38.95 +/- 14.59 years (range, 18-83), 94% were female, and 59.3%
      had children. An abnormality in the images presented was identified by 1613
      (98.4%) participants. The most commonly used search terms were: "white," "pupil,"
      "photo," and "eye" reaching a variety of appropriate websites or links to print
      or social media articles. Conclusions: Different words or phrases were used to
      describe the same observation of photoleukocoria leading to a range of websites.
      Variations in the description of observed signs and search words influenced the
      sites reached, information obtained, and subsequent help-seeking intentions.
      Translational Relevance: Identifying the most commonly used search terms for
      photoleukocoria is an important step for search engine optimization. Being
      directed to the most appropriate websites informing of the significance of
      photoleukocoria and the appropriate actions to take could improve delays in
      diagnosis of important pediatric eye disease such as retinoblastoma or cataract.

PMID- 29464133
TI  - Reduced Time to Breast Cancer Diagnosis with Coordination of Radiological and
      Clinical Care.
AB  - Introduction Diagnostic delays for breast problems is a current concern in
      British Columbia and diagnostic pathways for breast cancer are currently under
      review. Breast centres have been introduced in Europe and reported to facilitate
      diagnosis and treatment. Guidelines for breast centers are outlined by the
      European Society for Mastology (EUSOMA). A Rapid Access Breast Clinic (RABC) was
      developed at our hospital applying the concept of triple evaluation for all
      patients and navigation between clinicians and radiologists. We hypothesize that
      the Rapid Access Breast Clinic will decrease wait times to diagnosis and minimize
      duplication of services compared to usual care. Methods A retrospective review
      was undertaken looking at diagnostic wait times and the number of diagnostic
      centres involved for consecutive patients seen by breast surgeons with diagnostic
      workups performed either in the traditional system (TS) or the RABC. Only
      patients presenting with a new breast problem were included in the study. Results
      Patients seen at the RABC had a decreased time to surgical consultation (33 vs 86
      days, p<0.0001) for both malignant (36 vs 59 days, p=0.0007) and benign diagnoses
      (31 vs 95 days, p<0.0001). Furthermore, 13% of the patients referred to the
      surgeon in the TS without a diagnosis were eventually diagnosed with a malignancy
      and waited a mean of 84 days for initial surgical assessment. Of the patients
      seen at the RABC, 5% required investigation at more than one institution compared
      to 39% patients seen in the TS (p<0.0001). Cancer patients had a shorter time
      from presentation to surgery in the RABC (64 vs 92 days, p=0.009). Conclusion The
      establishment of the RABC has significantly reduced the time to surgical
      consultation, time to breast cancer surgery, and duplication of investigations
      for patients with benign and malignant breast complaints. It is feasible to
      introduce a EUSOMA-based breast clinic in the Canadian Health Care System and
      improvements in diagnostic wait times are seen. We recommend the expansion of
      coordinated care to other sites.

PMID- 29464134
TI  - Crowdsourced Curriculum Development for Online Medical Education.
AB  - In recent years online educational content, efforts at quality appraisal, and
      integration of online material into institutional teaching initiatives have
      increased. However, medical education has yet to develop large-scale online
      learning centers. Crowd-sourced curriculum development may expedite the
      realization of this potential while providing opportunities for innovation and
      scholarship. This article describes the current landscape, best practices, and
      future directions for crowdsourced curriculum development using Kern's framework
      for curriculum development and the example topic of core content in emergency
      medicine. A scoping review of online educational content was performed by a panel
      of subject area experts for each step in Kern's framework. Best practices and
      recommendations for future development for each step were established by the same
      panel using a modified nominal group consensus process. The most prevalent
      curriculum design steps were (1) educational content and (2) needs assessments.
      Identified areas of potential innovation within these steps included targeting
      gaps in specific content areas and developing underrepresented instructional
      methods. Steps in curriculum development without significant representation
      included (1) articulation of goals and objectives and (2) tools for curricular
      evaluation. By leveraging the power of the community, crowd-sourced curriculum
      development offers a mechanism to diffuse the burden associated with creating
      comprehensive online learning centers. There is fertile ground for innovation and
      scholarship in each step along the continuum of curriculum development.
      Realization of this paradigm's full potential will require individual developers
      to strongly consider how their contributions will align with the work of others.

PMID- 29464135
TI  - Impact of CyberKnife Radiosurgery on Median Overall Survival of Various
      Parameters in Patients with 1-12 Brain Metastases.
AB  - Introduction This study's objective is to assess various patient, tumor and
      imaging characteristics and to compare median overall survival (OS) of 150
      patients with 1-12 brain metastases post-CyberKnife radiosurgery (CKRS) (Accuray,
      Sunnyvale, California) alone. Methods Charts of 150 patients, from 2009-2014,
      treated with only CKRS for brain metastases were reviewed retrospectively for
      patient, tumor, and imaging characteristics. Parameters included demographics,
      Eastern Cooperative Oncology Group (ECOG) performance scores, number and control
      of extracranial disease (ECD) sites, cause of death (COD), histology, tumor
      volume (TV), and post-CKRS whole brain radiotherapy (WBRT). The imaging
      characteristics assessed were time of complete response (CR), partial response
      (PR), stable imaging or local failure (LF), and distal brain failure (DBF). The
      primary tumor Ki-67s of the breast carcinoma brain metastasis patients, who had
      the longest median OS of any group, were recorded when available. Results The
      predominant age group for the 150-patient cohort was the younger 17-65 years of
      age category, which was represented by 94 (62.7%). The 150-patient group had
      slightly more males, 79 (52.7%). The majority of 111 (74%) patients had an ECOG
      score of 1, 39 (26%) had 1 ECD site and uncontrolled ECD occurred in 112 (74.7%).
      The main COD was ECD in 106 (70.7%). The prevalent tumor histology was non-small
      cell lung carcinoma (88 of 150, 58.7%). The most common TV was 0-0.5 ccs (48 of
      150, 32%). The majority of 125 (83.3%) patients did not undergo post-CKRS WBRT.
      Imaging outcomes were local control (LC) (CR, PR, or stable imaging) in 119
      (79.3%), of whom 38 (25.3%) had CR, 56 (37.3%) PR and 25 (16.7%) stable imaging;
      LF was the outcome in 31 (20.7%) and DBF occured in 83 (55.3%). The median OS was
      13 months. Patients 17-65 years of age had a median OS of 13 months, while those
      66-88 years, had 12 months. Females versus males had median OS of 15 versus 12
      months. The most prolonged median OS of 21.5 months occurred in those with an
      ECOG score of 0. Patients with two ECD sites had a median OS of 14.5 months,
      while those with controlled ECD, 20.5 months. Patients with breast cancer brain
      metastases had the longest median OS of 23 months. The median OS for each of
      three (0-0.5 ccs, 0.6-1.5 ccs, 1.6-4.0 ccs) of four CKRS TV quartiles was 13
      months and for those with 4.1-28.5 ccs, 10 months. Median OS for patients with
      versus without post-CKRS WBRT was 23 versus 12 months. The longest median OS of
      18.5 months for post-CKRS imaging outcomes was in patients with CR; those with LF
      had a median OS of 11.5 months. Of nine patients with breast carcinoma brain
      metastases with available Ki-67s from primary tumor resections, the Ki-67 values
      were >= 34% for four patients with CR, PR and stable imaging outcomes, and < 34%
      for five patients with LF. Conclusions An ECOG score of 0, ECD control, breast
      carcinoma brain metastasis histology. undergoing WBRT post-CKRS and CR imaging
      outcomes, each resulted in a longer median OS. The Ki-67 proliferation indices
      from primary breast carcinoma resection correlated well with the brain imaging
      outcomes in a small preliminary study in the present study's breast carcinoma
      patients with brain metastases.

PMID- 29464136
TI  - Anesthetic Management of Pheochromocytoma Resection in Adults with Single
      Ventricle Physiology.
AB  - Survival rates for patients with palliated congenital heart disease are
      increasing, and an increasing number of adults with cyanotic congenital heart
      disease (CCHD) might require surgical resection of pheochromocytoma-paraganglioma
      (PHEO-PGL). A recent study supports the idea that patients with a history of CCHD
      and current or historical cyanosis might be at increased risk for developing PHEO
      PGL. We review the anesthetic management of two adults with single-ventricle
      physiology following Fontan palliation presenting for PHEO-PGL resection and
      review prior published case reports. We found the use of epidural analgesia to be
      safe and effective in the operative and postoperative management of our patients.

PMID- 29464137
TI  - Podcast Use in Undergraduate Medical Education.
AB  - Introduction Podcasts have become increasingly popular as a medium for free open
      access medical education (FOAM). However, little research has examined the use of
      these extracurricular audio podcasts as tools in undergraduate medical education.
      We aimed to examine knowledge retention, usage conditions, and preferences of
      undergraduate medical students at a Canadian university interacting with
      extracurricular podcasts. Methods Students enrolled in the undergraduate medical
      program at McMaster University volunteered to participate in this study. Two
      podcasts were created specifically for the purposes of this study, and online
      tests and surveys were sent to participants to gather data regarding user
      preferences of podcasts. In addition, we recorded changes in topic test scores
      before and after podcast exposure. Results Forty-two students were recruited to
      this study. Participants who completed the assessments demonstrated an effect of
      learning. Podcasts of 30 minutes or less were preferred in the majority of
      participants who had a preference in duration. The top three activities
      participants were engaged in while listening to the podcasts were driving (46%),
      completing chores (26%), and exercising (23%). A large number of participants who
      did not complete the study in its entirety cited a lack of time and podcast
      length to be the top two barriers to completion. Conclusion This is one of the
      first studies to examine extracurricular podcast-usage data and preferences in a
      Canadian undergraduate medical student population. This information may help
      educators and FOAM producers to optimize educational tools for medical education.

PMID- 29464138
TI  - The Use of Twitter by the Trauma and Orthopaedic Surgery Journals: Twitter
      Activity, Impact Factor, and Alternative Metrics.
AB  - Aim Social media (SoMe) platforms have become leading methods of communication
      and dissemination of scientific information in the medical community. They allow
      for immediate discussion and widespread engagement around important topics. It
      has been hypothesized that the activity on Twitter positively correlates with
      highly cited articles. The purpose of this study was to analyze the prevalence
      and activity of Trauma and Orthopaedic Surgery journals on Twitter, with the
      hypothesis that the impact factor is positively associated with the Twitter
      usage. Methods The top 50 Trauma and Orthopaedic Surgery journals, ranked by 2016
      Impact Factor were analyzed. The Twitter profiles of each journal or affiliated
      society were identified. Other SoMe platforms used were also recorded. The
      Twitonomy software (Digonomy Pty Ltd, New South Wales, Australia) was used to
      analyze the Twitter profiles over a one-year period. The Twitter Klout scores
      were recorded for each journal to approximate the SoMe influence. The Altmetric
      scores (the total number of mentions via alternative metrics) were also recorded.
      The statistical analysis was carried out to identify correlations between journal
      Impact Factors, SoMe activity, Twitter Klout scores and Altmetric scores. 
      Results Twenty-two journals (44%) were dedicated to the Twitter profiles.
      Fourteen journals (28%) were associated with societies that had profiles and 14
      journals (28%) had no Twitter presence. The mean Impact Factor overall was 2.16
      +/- 0.14 (range, 1.07-5.16). The journals with dedicated Twitter profiles had
      higher Impact Factors than those without (mean 2.41 vs. 1.61; P=0.005). A greater
      number of Twitter followers were associated with higher Impact Factors (R2 0.317,
      P=0.03). The journals with higher Twitter Klout scores had higher Impact Factors
      (R2 0.357, P=0.016). The Altmetric score was positively associated with an Impact
      Factor (R2 0.310, P=0.015). The journals with higher numbers of retweets (virtual
      citations in the Twittersphere) had higher Altmetric scores (R2 0.463, P=0.015).
      Conclusion The Trauma and Orthopaedic Surgery journals with dedicated Twitter
      profiles have higher Impact Factors than those without. The Altmetrics is likely
      to play a significant role in the literature evaluation going forward along with
      the traditional metrics. The engagement with the Twitter by Trauma and
      Orthopaedic surgeons should be encouraged.

PMID- 29464139
TI  - Role of Three-Dimensional Rotational Angiography in the Treatment of Spinal Dural
      Arteriovenous Fistulas.
AB  - Spinal dural arteriovenous fistulas (AVFs), being the most commonly encountered
      spinal vascular malformations, result in considerable morbidity with progressive
      spinal cord symptoms. A selective spinal digital subtraction angiography (DSA) is
      needed to confirm the diagnosis, to better evaluate the fine vascular structures
      and to plan therapy. With the introduction of three-dimensional rotational
      angiography (3D-RA), the information available for the treating physician has
      vastly increased. In the following article, we present a case series of four
      patients, in which the advantages of 3D-RA over the conventional biplane
      projections could be observed clearly.

PMID- 29464140
TI  - A Case Report of Recombinant Tissue Plasminogen Activator Use in a SPAN-100
      Positive Geriatric Patient with Thrombocytopenia.
AB  - Thrombocytopenia (platelet count: < 100,000/mm3) is considered a contraindication
      in the use of intravenous thrombolysis for acute ischemic stroke. Little
      literature exists regarding tissue plasminogen activator (tPA) usage in
      thrombocytopenic patients, especially in older patients. Age and stroke severity
      are major prognostic indicators of the risk of hemorrhagic transformation. The
      Stroke Prognostication using Age and NIH Stroke Scale (SPAN) index estimates a
      patient's risk of intracerebral hemorrhage (ICH) and clinical response to
      thrombolysis by combining age in years with the National Institutes of Health
      Stroke Scale (NIHSS) scores. If the total numeric sum is 100 or more, these
      individuals are considered SPAN-100-positive, while those with a sum less than
      100 are considered SPAN-100-negative patients. SPAN-100-positive patients are
      found to have a greater risk of ICH and poorer long-term outcomes than SPAN-100
      negative patients both with and without thrombolysis treatment. SPAN-100-positive
      patients are found to have a greater risk of ICH and poorer long-term outcomes
      than SPAN-100-negative patients both with and without thrombolysis treatment.
      Nonetheless, SPAN-100-positive patients treated with tPA have a reduced relative
      likelihood of severe disability or death than SPAN-100-positive patients not
      treated with tPA. We report a case of a SPAN-100-positive, 90-year-old community
      dwelling patient who presented with an acute ischemic stroke, an NIHSS score of
      14 with near complete left-sided plegia, and a platelet count of 85,000/mm3. Our
      patient was at increased risk of ICH and poor outcome regardless of tPA
      administration. However, due to the patient's high functional capacity prior to
      hospitalization and probable severe morbidity with poor recovery potential at his
      age, he was treated with tPA and showed a rapid improvement in neurological
      symptoms with no thrombolytic-associated morbidity. Thrombolytic therapy requires
      a case-by-case approach. Taking into account the patient's baseline and recovery
      potential is critical. Even absolute and relative contraindications, as they
      stand now, may need reconsideration, particularly those with little empiric
      evidence. More research is indicated to establish if thrombocytopenia should be
      reclassified as a relative rather than absolute contraindication to tPA.

PMID- 29464141
TI  - Survival and Failure Outcomes Predicted by Brain Metastasis Volumetric Kinetics
      in Melanoma Patients Following Upfront Treatment with Stereotactic Radiosurgery
      Alone.
AB  - Introduction The roles of early whole brain radiotherapy (WBRT) and upfront
      stereotactic radiosurgery (SRS) alone in the treatment of melanoma patients with
      brain metastasis remain uncertain. We investigated the volumetric kinetics of
      brain metastasis development and associations with clinical outcomes for melanoma
      patients who received upfront SRS alone. Methods Volumetric brain metastasis
      velocity (vBMV) was defined as the volume of new intracranial disease at the time
      of distant brain failure (DBF) for the first DBF (DBF1) and second DBF (DBF2)
      averaged over the time since initial or most recent SRS. Non-volumetric brain
      metastasis velocity (BMV) was calculated for comparison. Results Median overall
      survival (OS) for all patients was 7.7 months. Increasing vBMVDBF1 was associated
      with worsened OS (hazard ratio (HR): 1.10, confidence interval (CI): 1.02 - 1.18,
      p = .01). Non-volumetric BMVDBF1 was not predictive of OS after DBF1 (HR: 1.00,
      CI: 0.97 - 1.02, p = .77). Cumulative incidence of DBF2 at three months after
      DBF1 was 50.0% for vBMVDBF1 > 4 cc/yr versus (vs) 15.1% for vBMVDBF1 <= 4 cc/yr,
      (Gray's p-value = .02). Cumulative incidence of salvage WBRT at three months
      after DBF1 was 50.0% for vBMVDBF1 > 4 cc/yr vs 2.3% for vBMVDBF1 <= 4 cc/yr
      (Gray's p-value < .001). Conclusion In melanoma patients with brain metastasis,
      volumetric BMV was predictive of survival, shorter time to second DBF, and the
      need for salvage WBRT. Non-volumetric BMV, however, did not predict for these
      outcomes, suggesting that vBMV is a stronger predictor in melanoma.

PMID- 29464142
TI  - Decreased Renal Function Is Associated with Elevated CHA2DS2VASC and R2CHADS2
      Scores in Non-Valvular Atrial Fibrillation Patients Presenting with Stroke.
AB  - Introduction Atrial fibrillation (AF), the most common cardiac arrhythmia,
      affects approximately 2.3 million patients in the United States, costing around
      $26 billion. Atrial fibrillation is associated with a two- to seven-fold
      increased risk of stroke, one of the most serious complications. Chronic kidney
      disease affects approximately 13% of the US population and has been associated
      with higher rates of AF than the general population. In patients with chronic
      kidney disease (CKD), the risk of stroke increases as the glomerular filtration
      rate (GFR) decreases, especially in CKD stages three and four. Several risks
      stratification scores such as CHADS2 (congestive heart failure, hypertension,
      age, diabetes mellitus, stroke), CHA2DS2VASc (congestive heart failure,
      hypertension, age, diabetes mellitus, stroke, vascular disease, age, sex), and
      R2CHADS2 (renal failure, congestive heart failure, age, diabetes, stroke) scores
      are used for stroke risk assessment in patients with non-valvular atrial
      fibrillation (NVAF). This study investigates the association between renal
      functions and risk stratification scoring systems in patients with non-valvular
      AF presenting with stroke. Methods Using the convenience sampling method, 171
      subjects were selected from the eligible population (n = 386). A Pearson product
      moment correlation coefficient was calculated to determine the association
      between the GFR and each of the CHA2DS2VASc and R2CHADS2 scores. In addition, a
      Pearson product-moment correlation coefficient was calculated to determine the
      association between the CHA2DS2VASc and R2CHADS2 scores. Results The selected
      population represented 44.3% of the eligible subjects. Of these, 88% were
      Caucasian, 60% were female, and the mean age was 78 years. The mean CHA2DS2VASc
      score was six (range 2-9). The mean eGFR was 69.77 (range 6-108). Both the mode
      and the median CHA2DS2VASc score was four (range 2-8). A weak, but significant,
      negative correlation was found between renal function (eGFR) and the CHA2DS2VASc
      score (r = -0.263; p = 0.0005). There was a stronger negative correlation between
      the eGFR and R2CHADS2score (r = -0.70; p < 0.00001). The CHA2DS2VASc and
      R2CHADS2scoring schemes were significantly and positively correlated (r = 0.627;
      p < 0.00001). Discussion In NVAF patients presenting with stroke, renal failure
      is associated with higher CHA2DS2VASc and R2CHADS2 scores. One must consider
      renal failure (end-stage or non-end stage renal failure) as an additional
      potential risk factor for stroke when recommending anticoagulation in non
      valvular atrial fibrillation.

PMID- 29464143
TI  - Erythrodermic Psoriasis in a Man with Monoclonal B-cell Lymphocytosis.
AB  - Erythroderma is characterized by erythema involving greater than 90% of the body
      surface area and may be caused by several etiologies, including erythrodermic
      psoriasis. Psoriasis is an autoimmune skin and systemic condition characterized
      by erythematous and scaly plaques. Monoclonal B-cell lymphocytosis is an
      asymptomatic hematological disorder diagnosed by elevated, small, clonal B-cell
      counts in the peripheral blood. The characteristics of a 71-year-old man with new
      onset of erythrodermic psoriasis and concurrent monoclonal B-cell lymphocytosis
      are presented. The simultaneous development of these two conditions raises the
      possibility that they may share a related pathogenesis.

PMID- 29464144
TI  - Restrictive Strabismus Following Frontotemporal-orbitozygomatic Craniotomy.
AB  - The frontotempotal-orbitozygomatic craniotomy (FTOZ) is a standard approach for
      large sphenoid wing meningiomas (SWMs). Nevertheless, resection of these tumors
      is not without ophthalmologic risks. This series presents two patients with acute
      postoperative restrictive strabismus following tumor resection and orbital wall
      reconstruction. Forced duction testing and postoperative imaging revealed
      impingement of the lateral rectus muscle caused by an alloplastic implant and/or
      residual bone, prompting immediate orbitotomy and restoration of normal
      extraocular muscle function. This report highlights the intricacies of orbital
      reconstruction, as well as the need for intraoperative forced duction testing.

PMID- 29464145
TI  - Neurological Neonatal Birth Injuries: A Literature Review.
AB  - Birth injuries are a diverse set of traumas afflicting a newborn during labor
      and/or delivery. These range from temporary paralysis to hematomas. Herein, a
      comprehensive review of the birth injuries is presented, including the risk
      factors, classification of various paralyzes and nerve damage, as well as
      bleeding complications. The predicted outcomes and complications, as well as the
      treatment options for various birth injuries, are also discussed.

PMID- 29464146
TI  - Virtual Surgical Planning: The Pearls and Pitfalls.
AB  - Objective: Over the past few years, virtual surgical planning (VSP) has evolved
      into a useful tool for the craniofacial surgeon. Virtual planning and computer
      aided design and manufacturing (CAD/CAM) may assist in orthognathic, cranio
      orbital, traumatic, and microsurgery of the craniofacial skeleton. Despite its
      increasing popularity, little emphasis has been placed on the learning curve.
      Methods: A retrospective analysis of consecutive virtual surgeries was done from
      July 2012 to October 2016 at the University of Montreal Teaching Hospitals.
      Orthognathic surgeries and free vascularized bone flap surgeries were included in
      the analysis. Results: Fifty-four virtual surgeries were done in the time period
      analyzed. Forty-six orthognathic surgeries and 8 free bone transfers were done.
      An analysis of errors was done. Eighty-five percentage of the orthognathic
      virtual plans were adhered to completely, 4% of the plans were abandoned, and 11%
      were partially adhered to. Seventy-five percentage of the virtual surgeries for
      free tissue transfers were adhered to, whereas 25% were partially adhered to. The
      reasons for abandoning the plans were (1) poor communication between surgeon and
      engineer, (2) poor appreciation for condyle placement on preoperative scans, (3)
      soft-tissue impedance to bony movement, (4) rapid tumor progression, (5) poor
      preoperative assessment of anatomy. Conclusion: Virtual surgical planning is a
      useful tool for craniofacial surgery but has inherent issues that the surgeon
      must be aware of. With time and experience, these surgical plans can be used as
      powerful adjuvants to good clinical judgement.

PMID- 29464147
TI  - Superficial Inferior Epigastric Artery Flap Salvage Technique Using Deep Inferior
      Epigastric Artery Graft.
AB  - Superficial inferior epigastric artery (SIEA) flap salvage remains challenging,
      particularly in cases of arterial insufficiency due to vessel spasm, pedicle
      kinking, or thrombosis. The already small, short SIEA pedicle, in addition to its
      inherent tendency toward spasm, renders the SIEA flap more difficult to manage
      when anastomotic revision is required. Furthermore, arterial thrombosis will
      cause dilation of the internal mammary artery, exacerbating vessel mismatch. In
      our previously published experience with 145 SIEA flaps, no flap with
      postoperative arterial thrombosis was salvageable. Following this experience, a
      new salvage technique using deep inferior epigastric artery grafts has been
      utilized and is described here.

PMID- 29464148
TI  - Immediate Breast Reconstruction among Patients with Medicare and Private
      Insurance: A Matched Cohort Analysis.
AB  - Background: By eliminating economic hurdles, the Women's Health and Cancer Rights
      Act of 1998 represented a paradigm shift in the availability of breast
      reconstruction. Yet, studies report disparities among Medicare-insured women.
      These studies do not account for the inherent differences in age and
      comorbidities between a younger privately insured and an older Medicare
      population. We examined immediate breast reconstruction (IBR) utilization between
      a matched pre- and post-Medicare population. Methods: Using the Nationwide
      Inpatient Sample database (1992-2013), breast cancer patients undergoing IBR were
      identified. To minimize confounding medical variables, 64-year-old privately
      insured women were compared with 66-year-old Medicare-insured women. Demographic
      data, IBR rates, and complication rates were compared. Trend over time was
      plotted for both cohorts. Result: A total of 21,402 64-year-old women and 25,568
      66-year-old women were included. Both groups were well matched in terms of
      demographic type of reconstruction and complication rates. 72.3% of 64-year-old
      and 71.2 of % 66-year-old women opted for mastectomy. Of these, 25.5% (n = 3,941)
      of 64-year-old privately insured and 17.7% (n = 3,213) of 66-year-old Medicare
      insured women underwent IBR (P < 0.01). During the study period, IBR rates
      increased significantly in both cohorts in a similar cohort. Conclusion: This
      study demonstrates significant increasing IBR rates in both cohorts. Moreover,
      after an initial slower upward trend, after a decade, IBR in 66-year-old Medicare
      insured women approached similar rates of breast reconstruction among those with
      private insurance. Trends in unilateral versus bilateral mastectomy are also
      seen.

PMID- 29464149
TI  - Microsurgical Engineering: Bilateral Deep Inferior Epigastric Artery Perforator
      Flap with Flow-Through Intraflap Anastomosis.
AB  - Squamous cell carcinoma (SCC) of the head and neck affects a significant number
      of people around the world every year. Treatment generally entails surgical
      resection, radiotherapy, chemotherapy, or some combination of the three.
      Following resection, microsurgical reconstruction can provide definitive
      coverage, replace many tissue types simultaneously, and bring healthy tissue to
      irradiated wound beds. Microsurgical engineering, the manipulation and
      reorganization of native vascular tissue, can further augment the adaptability of
      free tissue transfer to complex, compromised wound beds. We present one such
      case. The patient described in the following report was treated for a recurrent
      SCC of the left face, which required extensive resection resulting in a complex,
      composite tissue defect with compromised vascular supply. Using the principals of
      microsurgical engineering, definitive coverage of the defect, with accept- able
      aesthetic result, was achieved via bipedicle, DIEP flap with flow-through
      intraflap anastomosis.

PMID- 29464150
TI  - Incisional Negative Pressure Wound Therapy for Prevention of Wound Healing
      Complications Following Reduction Mammaplasty.
AB  - Background: It has been proposed that negative pressure wound therapy (NPWT)
      applied prophylactically to a closed incision may decrease the incidence of wound
      complications. Patients undergoing reduction mammaplasty are at risk of wound
      complications such as delayed healing, infection, and dehiscence, and the
      bilateral nature of the surgery allows for a within-patient randomized study to
      evaluate incisional NPWT's effect in reducing healing complications. Methods: In
      this multicenter trial, 200 patients undergoing bilateral reduction mammaplasty
      were treated with PICO Single-Use NPWT System or standard wound-care dressings
      randomized to right or left breast for up to 14 days to enable within-patient
      comparison. Follow-up assessments were conducted to evaluate the difference in
      incision healing complications up to 21 days postsurgery. Healing complications
      (for the primary endpoint) were defined as delayed healing (incision not 100%
      closed by 7 days) and occurrence of dehiscence or infection within 21 days.
      Individual healing complications were assessed separately as secondary endpoints.
      Results: Significantly fewer healing complications (primary endpoint) were noted
      in NPWT-treated breasts [113 (56.8%)] versus standard care [123 (61.8%)]. The
      difference of 10 (5.0%) patients with fewer healing complications using NPWT was
      statistically significant (P = 0.004). NPWT also resulted in a significantly
      lower incidence of dehiscence (secondary endpoint) compared with standard care
      [32 patients (16.2%) versus 52 patients (26.4%)] by day 21, a relative reduction
      of 38% (P < 0.001). Conclusions: This is the first major prospective, within
      patient, randomized, controlled, multicenter study to provide evidence for an
      incisional NPWT strategy to reduce healing complications.

PMID- 29464151
TI  - The Pedicled LICAP Flap Combined with a Free Abdominal Flap In Autologous Breast
      Reconstructions.
AB  - Background: Previous surgery or slim body configuration can limit the size of the
      available abdominal flap in autologous breast reconstruction. However, redundant
      skin and subcutaneous tissue lateral to the mastectomy site can be utilized as
      the pedicled lateral intercostal artery perforator (LICAP) flap. This study
      evaluates the combination of a free abdominal flap and a pedicled LICAP flap to
      achieve increased breast size and improved cosmetic outcome. Methods: Patients
      undergoing secondary autologous breast reconstruction were included in a
      prospective study. The combination with a LICAP flap was used for women with
      insufficient abdominal flap tissue in relation to the desired breast size. The
      authors also assessed their modification of the original lateral thoracodorsal
      flap design to improve the aesthetic outcome. Results: In 109 patients, 121 free
      abdominal flaps were performed. The combination with a pedicled LICAP flap was
      used in 82 free abdominal flap reconstructions (68%). The LICAP flap provided
      additional volume and resulted in better projection and ptosis of the neo-mamma.
      The overall complication rate for the LICAP flaps was 26 %; all minor
      complications. Despite combining flaps, the majority of patients needed
      additional surgery to improve breast symmetry. Breast reduction of the native
      breast was the most common symmetrizing procedure. Conclusion: In selected
      patients with insufficient abdominal flap tissue, a combination of a free
      abdominal flap and a pedicled LICAP flap is a valuable option to increase breast
      size and cosmetic outcome. Additional symmetrizing surgery might still be
      necessary.

PMID- 29464152
TI  - Light-emitting Diode Transilluminator for the Identification of Recipient Veins
      in Finger Reconstruction.
AB  - Supplemental Digital Content is available in the text.

PMID- 29464153
TI  - SSET Project: Cost-effectiveness Analysis of Surgical Specialty Emergency Trays
      in the Emergency Department.
AB  - Background: We hypothesize that reusable, on-site specialty instrument trays
      available to plastic surgery residents in the emergency department (ED) for
      bedside procedures are more cost-effective than disposable on-site and remote re
      usable operating room (OR) instruments at our institution. Methods: We completed
      a cost-effectiveness analysis comparing the use of disposable on-site kits and
      remote OR trays to a hypothetical, custom, reusable tray for ED procedures
      completed by PRS residents. Material costs of existing OR trays were used to
      estimate the purchasing and use-cost of a custom on-site tray for the same
      procedures. Cost of per procedure 'consult time' was estimated using procedure
      and resident salary. Results: Sixteen bedside procedures were completed over a
      4.5 month period. A mean of 2.14 disposable kits were used per-procedure. Mean
      consultation time was 1.66 hours. Procedures that used OR trays took 3 times as
      long as procedures that used on-site kits (4 vs. 1.1 hours). Necessary,
      additional instruments were unavailable for 75% of procedures. Mean cost of using
      disposable kits and OR trays was $115.03/procedure versus an estimated
      $26.67/procedure cost of using a custom tray, yielding $88.36/procedure cost
      savings. Purchase of a single custom tray ($1,421.55) would be redeemed after 2.3
      weeks at 1 procedure/day. Purchasing 4 trays has projected annual cost-savings of
      $26,565.20. Conclusion: The purchase of specialized procedure trays will yield
      valuable time and cost-savings while providing quality patient care. Improving
      time efficiency will help achieve the Accreditation Council of Graduate Medical
      Education (ACGME) goals of maintaining resident well-being and developing quality
      improvement competency.

PMID- 29464154
TI  - V-shaped Internal Nasal Vestibular Flap for Reconstruction of Iatrogenic
      Columellar Defect.
AB  - Columella is an important structure in the center of the face, and its structural
      integrity has an important functional, social, and psychological role. Columella
      reconstruction can be very challenging for surgeons and the ideal technique
      remains elusive. This article describes a reconstruction technique in a young
      woman with columella necrosis due to nasal continuous positive airway pressure
      treatment. The method of reconstruction described here, with a V-shaped internal
      nasal vestibular flap and a cartilage grafts from lateral crura, is simple and
      easily reproducible, providing an optimal aesthetic result and in addition the
      donor site does not create a secondary deformity by disrupting normal anatomy.

PMID- 29464155
TI  - Single-Stage Breast Reconstruction Using an All-In-One Adjustable
      Expander/Implant.
AB  - Background: When tissue expansion is necessary in breast reconstruction, a single
      stage approach is possible using adjustable expander/implants, with or without
      the use of acellular dermal matrix. We aimed to present the senior author's
      single-stage experience over a period of 12 years using combined
      expander/implants in breast reconstruction. Methods: This is a Single
      institution, retrospective review of breast reconstruction with combined
      expander/implants from 2002 to 2014. Logistic regression was performed to
      evaluate the impact of multiple variables on long-term outcomes. Results: A total
      of 162 implants in 105 patients were included in this study. Mean follow-up time
      was 81.7 months (SD, +/- 39.2; range, 15-151). Complication rates were as
      follows: 0.62% extrusion, 1.2% mastectomy flap necrosis, 1.2% hematoma, 1.9%
      dehiscence, 2.5% seroma, 4.9% infection, and 15.4% deflation. The following
      associations were identified by logistic regression: adjuvant radiotherapy and
      capsular contracture (P = 0.034), tumor size and deflation (P = 0014), and
      smoking history and infection (P = 0.013). Conclusions: Overall, 81% of breasts
      were successfully reconstructed in a single stage. Single-stage reconstruction
      using all-in-one expander/implants reduces costs by eliminating the need for a
      second procedure under general anesthesia and can achieve results comparable with
      other alloplastic reconstructions reported in the literature.

PMID- 29464156
TI  - Structural and Mechanical Comparison of Human Ear, Alar, and Septal Cartilage.
AB  - Background: In the human ear and nose, cartilage plays a key role in establishing
      its form and function. Interestingly, there is a noticeable paucity on
      biochemical, structural, and mechanical studies focused on facial cartilage. Such
      studies are needed to provide elementary knowledge that is fundamental to tissue
      engineering of cartilage. Therefore, in this study, a comparison is made of the
      biochemical, structural, and mechanical differences between ear, ala nasi, and
      septum on the extracellular matrix (ECM) level. Methods: Cartilage samples were
      harvested from 10 cadaveric donors. Each sample was indented 10 times with a
      nanoindenter to determine the effective Young's modulus. Structural information
      of the cartilage was obtained by multiple-photon laser scanning microscopy
      capable of revealing matrix components at subcellular resolution. Biochemistry
      was performed to measure glycosaminoglycan (GAG), DNA, elastin, and collagen
      content. Results: Significant differences were seen in stiffness between ear and
      septal cartilage (P = 0.011) and between ala nasi and septal cartilage (P =
      0.005). Elastin content was significantly higher in ear cartilage. Per cartilage
      subtype, effective Young's modulus was not significantly correlated with cell
      density, GAG, or collagen content. However, in septal cartilage, low elastin
      content was associated with higher stiffness. Laser microscopy showed a distinct
      difference between ear cartilage and cartilage of nasal origin. Conclusion:
      Proposed methods to investigate cartilage on the ECM level provided good results.
      Significant differences were seen not only between ear and nasal cartilage but
      also between the ala nasi and septal cartilage. Albeit its structural similarity
      to septal cartilage, the ala nasi has a matrix stiffness comparable to ear
      cartilage.

PMID- 29464157
TI  - Clinical Significance of Venous Anomalies in Syndromic Craniosynostosis.
AB  - Background: The pattern of cranial venous drainage in syndromic craniosynostosis
      is unpredictable and not adequately understood. Collateral channels substitute
      for stenotic venous sinuses and pose potential risk for surgical intervention.
      The purpose of this study was to analyze the patterns of venous drainage in
      patients with syndromic craniosynostosis and their influence on operative
      planning and morbidity. Methods: A retrospective study of patients with syndromic
      craniosynostosis from 2000 to 2013 was performed. Demographic data were collected
      including phenotype and associated pathologies. Pre- and/or postoperative venous
      imaging was reviewed for venous sinus stenosis, collateral emissaries, and
      persistent fetal sinuses. Categorization of anomalous venous drainage was
      performed, and the relationship with surgical morbidity was assessed. Results:
      Forty-one patients were identified. Anomalies were present in 31 patients (76%)
      consisting of dural sinus stenosis in 28 (68%), dilated emissaries in 26 (63%),
      and fetal sinuses in 7 (17%). Pfeiffer syndrome was most commonly associated with
      anomalous drainage (100%). Venous anomalies were associated with elevated
      intracranial pressure (ICP), shunted hydrocephalus, Chiari malformations, and
      sleep apnea. In 5 cases, the surgical plan was adjusted based on anomalous
      anatomy. No mortalities occurred. Intraoperative complication rate was 7.3%, all
      with anomalous drainage. Median estimated blood loss was 1,100 cc for patients
      with anomalies versus 400 cc without anomalies (P = 0.181). Conclusion: Cranial
      venous anomalies are commonly detected in patients with syndromic
      craniosynostosis and may affect surgical morbidity and outcome with a higher
      estimated blood loss, alteration of procedure, and postoperative morbidity.
      Detailed preoperative imaging of the venous drainage is therefore recommended in
      cases of syndromic synostosis.

PMID- 29464158
TI  - Hyperbaric Oxygen for Ischemia due to Injection of Cosmetic Fillers: Case Report
      and Issues.
AB  - Natural and synthetic fillers have revolutionized aesthetic facial rejuvenation
      and soft-tissue augmentation. We present a case highlighting the dangers of
      filler self-injection. A 37-year-old woman self-injected a dermal filler around
      both temples. She immediately experienced left--side hearing loss, blanching over
      the left face, and pain. Prompt treatment with hyaluronidase, topical nitro
      paste, and warm compresses ensued. An emergency computed tomography angiogram
      showed occlusion of a superficial temporal artery branch. We treated her with
      enoxaparin, aspirin, dexamethasone, piperacillin-tazobactam, and intradermal
      lidocaine. After 6 hyperbaric oxygen therapy (HBO2) treatments in 3 days, the
      patient showed improvement in appearance with markedly decreased ischemic
      discoloration and her hearing returned to baseline. Algorithms for treating such
      injuries generally neglect HBO2. HBO2 is thought to be efficacious in these
      situations by a variety of mechanisms: oxygenation of ischemic tissues, reduction
      of edema, amelioration of ischemic/reperfusion injury, promotion of angiogenesis
      and collagen maturation. Her resolved hearing highlights the utility of HBO2 in
      sudden hearing loss as well. Injectors should have guidelines for using product,
      not only on patients but staff as well. Filler courses should include handling
      complications and include HBO2 in their guidelines. Clinicians should remind
      patients to seek treatment from qualified clinicians. The goal of a bargain price
      using self-injection may quickly become expensive and disfiguring.

PMID- 29464159
TI  - The Use of Vibrational Energy to Isolate Adipose-Derived Stem Cells.
AB  - Background: Adipose-derived stem cell (ADSC)-based treatments have the potential
      to treat numerous soft-tissue pathologies. It would be beneficial to develop an
      efficient and reliable intraoperative, nonenzymatic method of isolating ADSCs for
      clinical use. This study aims to determine the (1) viability and proliferative
      capacity of ADSCs after exposure to vibrational energies and (2) efficacy of
      vibrational energy as a method of ADSC isolation from surgically harvested
      infrapatellar fat pad (IFP). Methods: Cultured ADSCs were exposed to 15 minutes
      of vibration (60 Hz) with displacements ranging from 0 to 2.5 mm to assess cell
      viability and proliferation. Then, arthroscopically harvested adipose tissue
      (IFP; n = 5 patients) was filtered and centrifuged to separate the stromal
      vascular fraction, which was exposed to 15 minutes of vibration (60 Hz; 1.3 mm or
      2.5 mm displacement). A viability analysis was then performed along with
      proliferation and apoptosis assays. Results: Vibration treatment at all
      displacements had no effect on the viability or proliferation of the cultured
      ADSCs compared with controls. There was an increased apoptosis rate between the
      2.5 mm displacement group (7.53%) and controls (5.17%; P < 0.05) at day 1, but no
      difference at days 2, 3, and 14. ADSCs were not isolated from the IFP tissue
      after vibration treatment. Conclusions: ADSCs maintained viability and
      proliferative capacity after 15 minutes of vibration at 60 Hz and 2.5 mm
      displacement. ADSCs were not isolated harvested IFP tissue after the application
      of vibrational energy.

PMID- 29464160
TI  - Earfold Implantable Clip System for Correction of Prominent Ears: Analysis of
      Safety in 403 Patients.
AB  - Background: The Earfold system, a new treatment for the correction of prominent
      ears, consists of 3 components: the Earfold implant, the Earfold introducer, and
      the Prefold positioner. Methods: This is an interim report based on an ongoing
      analysis of safety in a series of patients treated for prominent ears with the
      Earfold implant between February 2013 and September 2014. Safety was assessed
      based on adverse event reports and the need for implant revision; follow-up is
      ongoing. Results: Seven surgeons used 1,200 Earfold implants to treat 403
      patients (ages, 7-70 years; 63% male); the time since the initial implant
      procedure now ranges from 30 to 48 months. To date, 145 patients (36%) have
      returned for a follow-up visit (mean, 7.7 months [range, 1-34 months]). Adverse
      events requiring intervention have affected 39 of 403 (9.7%) patients; these
      include implant revisions (n = 17 [4.2%], most often due to implant visibility),
      skin erosion over the implant (n = 15 [3.7%]), and infection (n = 7 [1.7%]).
      Bleeding, recurrence of prominence, hematoma, deformity, or adverse scarring did
      not occur. Conclusions: This interim analysis has shown that Earfold prominent
      ear correction system is associated with relatively few adverse events that
      require intervention; a small number of patients experienced infection, implant
      extrusion, or implant visibility that required revision. Most adverse events were
      related to either patient selection or technical errors at implantation. It is
      expected that with continued use of Earfold by surgeons experienced in otoplasty,
      the adverse event incidence will decrease.

PMID- 29464161
TI  - Complications following Nipple-Sparing Mastectomy and Immediate Acellular Dermal
      Matrix Implant-based Breast Reconstruction-A Systematic Review and Meta-analysis.
AB  - Background: Acellular dermal matrix was introduced in breast reconstruction in
      2001 and is gradually becoming a standard component for immediate breast
      reconstruction and nipple-sparing mastectomy. The reconstructive technique allows
      for improved aesthetic outcomes. However, there seems to be uncertainty regarding
      complication rates. The aim of this review was to systematically evaluate
      complication rates related to this method. Methods: This systematic review was
      conducted according to the recommendations outlined in the Cochrane Handbook for
      reviews and reported in line with the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses statement. Relevant databases were searched for in the
      literature concerning the use of acellular dermal matrix in implant-based nipple
      sparing mastectomy and immediate breast reconstruction. All studies underwent
      detailed quality assessment. Summarized outcome rates were computed using meta
      analysis. Results: Nine of 1,039 studies were eligible for inclusion yielding 778
      procedures. The quality was acceptable for all included studies. The meta
      analysis found the rate of skin necrosis to be 11%, nipple necrosis 5%, infection
      in 12%, hematoma in 1%, treated seroma in 5%, explantation 4%, and unplanned
      return to the operating room in 9%. Conclusion: The use of acellular dermal
      matrix in nipple-sparing mastectomy and implant-based breast reconstruction can
      be done with acceptable complication rates in selected patients. We recommend
      future studies to include specific definitions when reporting complication rates.
      Furthermore, future studies should elaborate on demographic characteristics of
      the included study samples and include predictor analysis to enhance knowledge of
      high risk patients.

PMID- 29464162
TI  - Hinge Flap with Triangular Extension for Reconstruction of Pharyngocutaneous and
      Laryngocutaneous Fistulas.
AB  - Hinge flaps are commonly used for closure of a pharyngocutaneous fistula (PCF) or
      laryngocutaneous fistula. These flaps are employed to augment the wall of the
      pharynx or larynx, but the junction between the reconstructed and native lumens
      can eventually become narrow and irregular after reconstruction with standard
      hinge flaps. We devised a method of adding a triangular extension to the end of
      either or both flaps and used it to treat 3 patients. In 1 patient who developed
      a PCF (4 * 10 cm) after laryngectomy followed by radiotherapy, the fistula was
      closed with 2 hinge flaps. One flap had a caudal triangular extension. The
      residual skin defect was covered by a pedicled latissimus dorsi musculocutaneous
      flap. Another patient who developed a PCF (2.5 * 3 cm) after laryngectomy
      underwent 2-stage reconstruction using a buccal mucosal graft with a triangular
      extension, followed by 2 hinge flaps. A patient who developed an laryngocutaneous
      fistula (1 * 2 cm) after radiotherapy and subsequent partial laryngectomy
      underwent reconstruction using 2 hinge flaps, each of which had a triangular
      extension. The skin defect was covered by another flap. Postoperative CT or video
      fluoroscopic examination of swallowing showed a smooth lumen with no strictures
      in all 3 patients. The triangular extension of the hinge flap supplements the
      pharyngeal/laryngeal wall at the junction between the reconstructed and intact
      regions, thus avoiding postoperative stricture. Especially with PCF
      reconstruction, restoration of a smooth luminal surface minimizes dysphagia.

PMID- 29464163
TI  - Innovative Use of Thighplasty to Improve Prosthesis Fit and Function in a
      Transfemoral Amputee.
AB  - Background: Excess residual limb fat is a common problem that can impair
      prosthesis control and negatively impact gait. In the general population,
      thighplasty and liposuction are commonly performed for cosmetic reasons but not
      specifically to improve function in amputees. The objective of this study was to
      determine if these procedures could enhance prosthesis fit and function in an
      overweight above-knee amputee. Methods: We evaluated the use of these techniques
      on a 50-year-old transfemoral amputee who was overweight. The patient underwent
      presurgical imaging and tests to measure her residual limb tissue distribution,
      socket-limb interface stiffness, residual femur orientation, lower-extremity
      function, and prosthesis satisfaction. A medial thighplasty procedure with
      circumferential liposuction was performed, during which 2,812 g (6.2 lbs.) of
      subcutaneous fat and skin was removed from her residual limb. Imaging was
      repeated 5 months postsurgery; functional assessments were repeated 9 months
      postsurgery. Results: The patient demonstrated notable improvements in socket fit
      and in performing most functional and walking tests. Her comfortable walking
      speed increased 13.3%, and her scores for the Sit-to-Stand and Four Square Step
      tests improved over 20%. Femur alignment in her socket changed from 8.13 to 4.14
      degrees, and analysis showed a marked increase in the socket-limb interface
      stiffness. Conclusions: This study demonstrates the potential of using a routine
      plastic surgery procedure to modify the intrinsic properties of the limb and to
      improve functional outcomes in overweight or obese transfemoral amputees. This
      technique is a potentially attractive option compared with multiple reiterations
      of sockets, which can be time-consuming and costly.

PMID- 29464164
TI  - An Enhanced Recovery after Surgery Pathway for Microvascular Breast
      Reconstruction Is Safe and Effective.
AB  - Background: The aim of this study was to develop, implement, and evaluate a
      standardized perioperative enhanced recovery after surgery (ERAS) clinical care
      pathway in microsurgical abdominal-based breast reconstruction. Methods:
      Development of a clinical care pathway was informed by the latest ERAS guideline
      for breast reconstruction. Key features included shortened preoperative fasting,
      judicious fluids, multimodal analgesics, early oral nutrition, early Foley
      catheter removal, and early ambulation. There were 3 groups of women in this
      cohort study: (1) traditional historical control; (2) transition group with
      partial implementation; and (3) ERAS. Narcotic use, patient-reported pain scores,
      antiemetic use, time to regular diet, time to first walk, hospital length of
      stay, and 30-day postoperative complications were compared between the groups.
      Results: After implementation of the pathway, the use of parenteral narcotics was
      reduced by 88% (traditional, 112 mg; transition, 58 mg; ERAS, 13 mg; P < 0.0001),
      with no consequent increase in patient-reported pain. Patients in the ERAS cohort
      used less antiemetics (7.0, 5.3, 2.2 doses, P < 0.0001), returned to normal diet
      19 hours earlier (46, 39, 27 hours, P < 0.0001), and walked 25 hours sooner (75,
      70, 50 hours, P < 0.0001). Overall, hospital length of stay was reduced by 2 days
      in the ERAS cohort (6.6, 5.6, 4.8 days, P < 0.0001), without an increase in rates
      of major complications (9.5%, 10.1%, 8.3%, P = 0.9). Conclusions: A clinical care
      pathway in microsurgical breast reconstruction using the ERAS Society guideline
      promotes successful early recovery.

PMID- 29464165
TI  - Reexploring the Anatomy of the Distal Humerus for its Role in Providing
      Vascularized Bone.
AB  - Background: The lateral arm flap is used for composite defects in need of
      vascularized soft tissue, skin, and bone. From its original description, the
      distal humeral metaphysis can be included with the flap, supplied by the
      periosteal extensions of the posterior branch of the radial collateral artery. We
      sought to reexplore the anatomy of the lateral arm to determine its utility as a
      donor site for vascularized bone. Methods: Twelve fresh, silicone-injected
      cadaver dissections were performed. Arteriovenous anatomy, pedicle length and
      diameter, and anatomic variability as well as photo documentation was recorded.
      Results: The distal extent of the deltoid, lateral intermuscular septum and
      lateral humeral epicondyle were identified before the dissection. A
      septocutaneous perforator was consistently located 10 cm proximal to the lateral
      humeral epicondyle, which could be used for a skin paddle to monitor. Harvest of
      a 1.5 cm * 2 cm corticocancellous bone graft was performed. Average pedicle
      length was 9.1 +/- 1.1 cm, and average pedicle diameter was 1.74 +/- 0.52 mm. The
      inferior lateral cutaneous nerve of the arm and the posterior cutaneous nerve of
      the forearm were consistently identified and preserved. Conclusion: The
      predictable anatomy of the lateral distal humerus make it an ideal donor site for
      small segments of vascularized bone.

PMID- 29464166
TI  - Successful Hand Replantation in a Case of Total Avulsion without Vein Graft.
AB  - Replantation is the reattachment of a severed body part, with attempts to restore
      neurovascular and musculoskeletal integrity, function, and aesthetics. On
      September 7, 1964, the first extremity replantation-a completely amputated hand
      by vascular anastomosis technique was successfully performed.1 Soon after, the
      first replantation of a complete thumb amputation using microvascular anastomosis
      in a human was successfully conducted by Komatsu et al.2 in 1968. The overall
      success rate of limb replantation surgery is around 83.2%.3 The mechanism of
      injury plays a role in the outcome; guillotine amputations-for example-carry a
      better prognosis than crush amputations.4 We present a case report of a 36-year
      old male patient who presented with a total avulsion of the right hand with
      multiple fracture levels at the level of trans-carpal, distal radius extra
      articulation fracture, and total avulsion of the hand. The patient was managed by
      a multidisciplinary team who were able to reattach his hand successfully with
      good functional outcome.

PMID- 29464167
TI  - Use of Viable Cryopreserved Placental Membrane as an Adjunct to Facial Keloid
      Resection.
AB  - Keloids are the physical manifestation of an exaggerated inflammatory response
      resulting in excess collagen deposition. The resulting fibroproliferative mass
      can be distressing for patients due to appearance, pruritus, and/or pain. Despite
      extensive research into the pathophysiology of keloid formation and the
      development of numerous treatments, keloids remain a challenge to treat. Even
      when the initial treatment is successful, a risk of recurrence remains. Basic
      science research into viable cryopreserved placental membranes and viable
      cryopreserved umbilical tissue has demonstrated their anti-inflammatory and anti
      fibrotic effects, which may decrease keloid recurrence after excision. In this
      article, we present the first-reported case of viable cryopreserved placental
      membrane, with living mesenchymal stem cells, to treat a painful preauricular
      keloid in conjunction with surgical resection.

PMID- 29464168
TI  - Treatment Strategies for Hypopigmentation in the Context of Burn Hypertrophic
      Scars.
AB  - Dyspigmentation in burn scars can contribute to the development of psychosocial
      complications after injury and can be detrimental to social reintegration and
      quality of life for burn survivors. Although treatments for skin lightening to
      treat hyperpigmentation have been well reviewed in the literature, skin-darkening
      strategies to treat hypopigmentation have not. The following potential treatment
      options in the context of burn hypertrophic scar will be discussed: use of the
      melanocyte-keratinocyte transplantation procedure, use of ectopic synthetic
      analogues of alpha-melanocyte stimulating hormone to initiate melanogenesis, and
      use of FK506 to induce melanogenesis. A proposed future direction of research in
      laser-assisted drug delivery of inducers of local melanin production, with the
      hope of developing a targeted, effective approach to dyspigmentation in
      hypertrophic scar is also discussed.

PMID- 29464169
TI  - Enhanced Preoperative Deep Inferior Epigastric Artery Perforator Flap Planning
      with a 3D-Printed Perforasome Template: Technique and Case Report.
AB  - Optimizing preoperative planning is widely sought in deep inferior epigastric
      artery perforator (DIEP) flap surgery. One reason for this is that rates of fat
      necrosis remain relatively high (up to 35%), and that adjusting flap design by an
      improved understanding of individual perforasomes and perfusion characteristics
      may be useful in reducing the risk of fat necrosis. Imaging techniques have
      substantially improved over the past decade, and with recent advances in 3D
      printing, an improved demonstration of imaged anatomy has become available. We
      describe a 3D-printed template that can be used preoperatively to mark out a
      patient's individualized perforasome for flap planning in DIEP flap surgery. We
      describe this "perforasome template" technique in a case of a 46-year-old woman
      undergoing immediate unilateral breast reconstruction with a DIEP flap. Routine
      preoperative computed tomographic angiography was performed, with open-source
      software (3D Slicer, Autodesk MeshMixer and Cura) and a desktop 3D printer
      (Ultimaker 3E) used to create a template used to mark intra-flap, subcutaneous
      branches of deep inferior epigastric artery (DIEA) perforators on the abdomen. An
      individualized 3D printed template was used to estimate the size and boundaries
      of a perforasome and perfusion map. The information was used to aid flap design.
      We describe a new technique of 3D printing a patient-specific perforasome
      template that can be used preoperatively to infer perforasomes and aid flap
      design.

PMID- 29464170
TI  - Adjuvant Therapy for Revision Rhinoplasty of Contracted Nose Using
      Polydeoxyribonucleotide and Invasive Bipolar Radiofrequency.
AB  - Most cases of severely contracted nose require revision rhinoplasty and
      septoplasty, wherein preoperative and/or intraoperative expansion of nasal soft
      tissue is necessary for tension-free revision surgery. The present study aimed to
      evaluate the efficacy and safety of pre- and postoperative adjuvant therapy using
      polydeoxyribonucleotide (PDRN) and invasive, pulsed-type, bipolar, alternating
      current radiofrequency (RF) for revision surgery of a contracted nose. In total,
      30 patients were treated with 16 sessions (8 preoperative sessions and 8
      postoperative sessions) of intralesional injection of PDRN and invasive RF
      treatment using microneedle electrodes at 1-week intervals. One week after the
      final combined pretreatment using PDRN and invasive bipolar RF, the skin of
      contracted noses was sufficiently softened, and nasal skin mobility was notably
      improved in all the patients. During revision rhinoplasty and septoplasty, the
      contracted nasal skin in each patient was adequately released for proper covering
      of the nasal tip without tension. Postoperatively, 8 sessions of adjuvant therapy
      elicited marked clinical improvements in persistent nasal tip dimpling and
      contracture, septal deviation, and warping from the incomplete recovery of nasal
      contracture after revision surgery. In conclusion, our pre- and postoperative
      adjuvant therapies using PDRN and invasive bipolar RF remarkably improved the
      therapeutic outcomes of revision rhinoplasty and septoplasty for contracted skin
      of the nose without major side effects.

PMID- 29464171
TI  - Dimensional Error in Rapid Prototyping with Open Source Software and Low-cost 3D
      printer.
AB  - Rapid prototyping models (RPMs) had been extensively used in craniofacial and
      maxillofacial surgery, especially in areas such as orthognathic surgery,
      posttraumatic or oncological reconstructions, and implantology. Economic
      limitations are higher in developing countries such as Mexico, where resources
      dedicated to health care are limited, therefore limiting the use of RPM to few
      selected centers. This article aims to determine the dimensional error of a low
      cost fused deposition modeling 3D printer (Tronxy P802MA, Shenzhen, Tronxy
      Technology Co), with Open source software. An ordinary dry human mandible was
      scanned with a computed tomography device. The data were processed with open
      software to build a rapid prototype with a fused deposition machine. Linear
      measurements were performed to find the mean absolute and relative difference.
      The mean absolute and relative difference was 0.65 mm and 1.96%, respectively (P
      = 0.96). Low-cost FDM machines and Open Source Software are excellent options to
      manufacture RPM, with the benefit of low cost and a similar relative error than
      other more expensive technologies.

PMID- 29464172
TI  - Free Flap Survival Despite Internal Jugular Vein Thrombosis in Head and Neck
      Reconstruction.
AB  - Microvascular free tissue transfer is one of the most common techniques of
      reconstruction for complex head and neck surgical defects. Generally, venous
      thrombosis is more likely to occur than arterial thrombosis in vascular
      anastomosis. Thus, recipient veins must be chosen carefully. Although the
      internal jugular vein is preferred as a recipient vein by many microsurgeons,
      internal jugular vein thrombosis is a potential complication, as shown in our
      report. Therefore, we consider that the external jugular vein still is an option
      as a recipient for venous anastomosis and that it is better to perform multiple
      vein anastomoses with 2 different venous systems, such as the internal and
      external jugular systems, than anastomoses within the same venous system.

PMID- 29464173
TI  - Temporomandibular Joint Septic Arthritis.
AB  - Infection of the temporomandibular joint (TMJ) is a rare pediatric condition
      resulting from the introduction of pathogens into the joint by hematogenous
      seeding, local extension, or trauma. Early recognition of the typical signs and
      symptoms including fever, trismus, preauricular swelling, and TMJ region
      tenderness are critical in order to initiate further evaluation and prevent
      feared complications of fibrosis, ankylosis, abnormal facial structure, or
      persistence of symptoms. Contrast-enhanced computed tomography with ancillary
      laboratory analysis including erythrocyte sedimentation rate, C-reactive protein,
      and white blood cell count are beneficial in confirming the suspected diagnosis
      and monitoring response to therapy. Initial intervention should include empiric
      parenteral antibiotics, early mandibular mobilization, and joint decompression to
      provide synovial fluid for analysis including cultures. This report describes a
      case of TMJ bacterial arthritis in a healthy 6-year-old male who was promptly
      treated nonsurgically with intravenous antibiotics and localized needle joint
      decompression with return to normal function after completion of oral antibiotics
      and physical therapy.

PMID- 29464174
TI  - Suture Technique to Prevent Air Leakage during Negative-Pressure Wound Therapy in
      Fournier Gangrene.
AB  - Background: The use of negative-pressure wound therapy (NPWT) for Fournier
      gangrene management is well documented; however, it is difficult to fixate
      GranuFoam dressings and maintain an airtight seal over the perineum area. We
      developed a simple method to facilitate GranuFoam fixation and improve airtight
      sealing. Methods: The Fournier's gangrene severity index (FGSI) score less than 9
      was collected in from January 2015 to October 2016. All 13 patients underwent
      fasciotomy, and NPWT was applied directly on fasciotomy wounds after the
      debridement of infected tissue. Partial wound closure was performed, and a
      portion of GranuFoam was inserted to facilitate fixation. The seal check was
      converted to a 0-10 scale score that was recorded every 4 hours during NPWT.
      Patient profiles including medical history, FGSI, method of wound closure, and
      length of stay were collected in this study. Results: The median age of the
      patients was 62 (38-76) years. The mean FGSI score was 4.3 +/- 3.1. The average
      duration of NPWT was 17.5 +/- 11.5 days, and the average seal check score was 0.8
      +/- 0.5. No seal check alarms were noted during the study. Successful wound
      closure was achieved in all patients without using additional reconstruction
      methods such as skin grafting or muscle flap coverage. Conclusions: The present
      results suggest that partial wound-edge closure and in situ GranuFoam fixation
      improve the NPWT leaks in Fournier gangrene wounds. Furthermore, this method is
      simple to learn and can be useful in applying NPWT to anatomically difficult
      areas.

PMID- 29464175
TI  - Quality Improvement in Facial Transplantation: Standard Approach for Novel
      Procedures.

PMID- 29464176
TI  - Latissimus Dorsi and Immediate Fat Transfer (LIFT) for Complete Autologous Breast
      Reconstruction.
AB  - Background: Despite the popularity of latissimus dorsi (LD) flap in breast
      reconstruction, a breast implant is often necessary to achieve sufficient volume.
      Prior reports describe fat grafting to the LD flap as a secondary procedure to
      correct contour deformities and improve volume. Our institution has instituted
      autologous breast reconstruction with an LD flap and immediate fat transfer
      (LIFT). Methods: A retrospective review of all patients undergoing the LIFT
      procedure was undertaken. Patient age, total volume of fat transfer, length of
      follow-up, need for adjuvant therapy, and complications were recorded. The
      procedure begins with harvest of the LD flap and fat. Prior to disorigination of
      the latissimus muscle, fat is injected into the flap. Flap harvest is then
      completed and inset to create a breast mound. Results: Eighteen patients
      underwent LIFT procedures over 3 years with an average follow-up of 8.7 months
      (range, 2-24). Four breasts (22.2%) had previously received adjuvant radiation
      therapy. The mean total fat grafting volume was 515.5 mL (range, 325-730) per
      breast. The average estimated fat graft take was 66.8% (range, 50-80%). Four
      patients (22.2%) experienced complications. Conclusion: Autologous augmentation
      of the LD flap with lipotransfer has been used to avoid placement of an implant.
      We improve the technique by performing lipotransfer during index reconstruction.
      Furthermore, we perform lipotransfer prior to disorigination of the LD muscle to
      minimize trauma to the flap and increase the efficiency of fat grafting. Our
      experience demonstrates that this technique is a viable autologous alternative to
      microsurgical breast reconstruction.

PMID- 29464177
TI  - TB or not TB? Mycobacterium celatum mimicking Mycobacterium tuberculosis: A case
      of mistaken identity.
AB  - Mycobacterium celatum is a slow-growing, non-tuberculous mycobacterium (NTM) and
      a rare cause of infection in humans. Infection occurs primarily by inhalation or
      direct inoculation from environmental sources, and this pathogen has been
      reported to cause localized infections in the lungs and lymph nodes of both
      immunocompetent and immunocompromised patients, and disseminated disease in
      immunocompromised patients. Here, we present a case of pulmonary infection with
      M. celatum in an immunocompetent 68-year-old male with clinical features similar
      to tuberculosis. The patient initially developed palpitations, worsening fatigue,
      night sweats, dyspnea, productive cough, and weight loss. Computed tomography
      angiogram of the chest revealed a right upper lobe pulmonary artery embolus and
      extensive biapical fibronodular cavitary densities. Two separate sputum samples
      were positive for acid-fast bacilli (AFB) and sputum cultures were positive for
      M. celatum. The patient responded well to treatment with clarithromycin,
      ciprofloxacin, and ethambutol. We advise physicians to consider M. celatum
      infection in the differential diagnosis of patients with symptoms and
      radiographic and microbiologic evidence suggestive of NTM pulmonary infection.

PMID- 29464178
TI  - Diagnostic Accuracy of Platelet Count and Platelet Indices in Noninvasive
      Assessment of Fibrosis in Nonalcoholic Fatty Liver Disease Patients.
AB  - Objective: Keeping in mind the rising prevalence of nonalcoholic fatty liver
      disease (NAFLD) and the need to establish noninvasive tests for its detection,
      the aim of our study was to investigate whether platelet count (PC), mean
      platelet volume (MPV), and platelet distribution width (PDW) can predict the
      presence of liver fibrosis in this group of patients. Methods: In 98 patients
      with NAFLD and 60 healthy volunteers, complete blood counts with automated
      differential counts were performed and values of PC, PDW, MPV, and PCT were
      analyzed. Results: Patients with NAFLD had lower PC and higher MPV, PCT, and PDW
      compared to the controls (P < 0.05). When NAFLD group was stratified according to
      severity of liver fibrosis, there was a statistically significant difference in
      the average values of PDW and PC between the groups (P < 0.05). Conclusion:
      Patients with NAFLD have significantly higher values of PCT, PDW, and MPV when
      compared to the healthy controls. Further studies are needed to establish their
      potential use for prediction of the degree of liver steatosis and fibrosis in
      NAFLD patients.

PMID- 29464179
TI  - Leukocyte Cell-Derived Chemotaxin 2-Associated Renal Amyloidosis: A Case Report.
AB  - Amyloidosis is a disorder characterized by the deposition of abnormal protein
      fibrils in tissues. Leukocyte cell-derived chemotaxin 2-associated amyloidosis is
      a recently recognized entity and is characterized by a distinctive
      clinicopathologic type of amyloid deposition manifested in adults by varying
      degrees of impaired kidney function and proteinuria. There are only a limited
      number of cases reported in the literature. We present a 64-year-old Hispanic
      female with a history of hypertension who was referred for chronic kidney disease
      management. The review of her laboratory tests revealed a serum creatinine of 1.5
      1.8 mg/dL and microalbuminuria (in the presence of a bland urine sediment) in the
      past year. She denied any history of diabetes, rheumatologic disorders or
      exposure to intravenous contrast, nonsteroidal anti-inflammatory drugs, herbals,
      and heavy metals. Serological workup was negative. A renal biopsy showed diffuse
      infiltration of glomerulus with pale eosinophilic material strongly positive for
      Congo red stain and a similar eosinophilic material in the interstitium, muscular
      arteries, and arterioles. Electron microscopy showed marked infiltration of the
      mesangium, capillary loops, and interstitium with haphazardly arranged fibrillary
      deposits (9.8 nm thick). Liquid chromatography tandem mass spectrometry confirmed
      leukocyte cell-derived chemotaxin 2 (LECT2) amyloid deposition. LECT2 amyloidosis
      (ALECT2) should be suspected in renal biopsy specimens exhibiting extensive and
      strong mesangial as well as interstitial congophilia. Individuals with LECT2
      renal amyloidosis have a varying prognosis. Therapeutic options include
      supportive measures and consideration of a kidney transplant for those with end
      stage renal disease.

PMID- 29464180
TI  - Lingguizhugan Decoction Protects against High-Fat-Diet-Induced Nonalcoholic Fatty
      Liver Disease by Alleviating Oxidative Stress and Activating Cholesterol
      Secretion.
AB  - Background: Nonalcoholic fatty liver disease (NAFLD) has become a leading cause
      of liver transplantation. Lingguizhugan decoction (LGZG), a classical Chinese
      herbal formula, has beneficial effects on NAFLD animal models. Our study examined
      the impact of LGZG on hepatic global transcriptome of high-fat-diet-induced NAFLD
      rats. Methods: Three groups of Wistar rats were included: normal, NAFLD model,
      and LGZG-treated NAFLD groups. Four weeks for the treatment, liver tissues were
      harvested for RNA sequencing. Differentially expressed genes (DEGs) and enriched
      pathways were detected on hepatic global transcriptome profile. Real-time PCR
      validated the regulatory patterns of LGZG on NAFLD rats. Results: DEGs between
      the NAFLD model and normal groups indicated the elevated peroxisome proliferator
      activated receptor (PPAR) and hedgehog signaling pathways in NAFLD rats. In bile
      secretion pathway, genes involved in cholesterol secretion were activated by LGZG
      treatment. Increased expression of antioxidant OSIGN1 and decreased expression of
      genes (AHR, IRF2BP2, and RASGEF1B) that induce oxidative stress and inflammation
      were observed in NAFLD rats treated with LGZG. The regulatory patterns of LGZG
      treatment on these oxidative stress-related genes were confirmed by real-time
      PCR. Conclusion: Our study revealed a "two-hits-targeting" mechanism of LGZG in
      the treatment for NAFLD: alleviating oxidative stress and activating cholesterol
      secretion.

PMID- 29464181
TI  - Diabetic Retinopathy in the Spontaneously Diabetic Torii Rat: Pathogenetic
      Mechanisms and Preventive Efficacy of Inhibiting the Urokinase-Type Plasminogen
      Activator Receptor System.
AB  - The spontaneously diabetic Torii (SDT) rat is of increasing preclinical interest
      because of its similarities to human type 2 diabetic retinopathy (DR). The system
      formed by urokinase-type plasminogen activator (uPA) and its receptor (uPAR) is a
      player in blood-retinal barrier (BRB) breakdown in DR. Here, we investigated
      whether in SDT rats, preventive administration of UPARANT, an inhibitor of the
      uPAR pathway, counteracts the retinal impairment in response to chronic
      hyperglycemia. Electroretinogram (ERG) monitoring was followed over time.
      Fluorescein-dextran microscopy, CD31 immunohistochemistry, quantitative PCR,
      ELISA, Evans blue perfusion, and Western blot were also used. UPARANT prevented
      ERG dysfunction, upregulation of vascular endothelial growth factor and
      fibroblast growth factor-2, BRB leakage, gliosis, and retinal cell death. The
      mechanisms underlying UPARANT benefits were studied comparing them with the acute
      streptozotocin (STZ) model in which UPARANT is known to inhibit DR signs. In SDT
      rats, but not in the STZ model, UPARANT downregulated the expression of uPAR and
      its membrane partners. In both models, UPARANT reduced the levels of
      transcription factors coupled to inflammation or inflammatory factors themselves.
      These findings may help to establish the uPAR system as putative target for the
      development of novel drugs that may prevent type 2 DR.

PMID- 29464182
TI  - Association between Knowledge-Attitude-Practices and Control of Blood Glucose,
      Blood Pressure, and Blood Lipids in Patients with Type 2 Diabetes in Shanghai,
      China: A Cross-Sectional Study.
AB  - Knowledge-attitude-practices (KAP) significantly impact the outcome of self
      management in patients with diabetes, yet the association between KAP and the
      combined control of the levels of blood glucose, blood pressure, and blood lipids
      in these patients remains uncertain. This community-based cross-sectional study
      was conducted from December 2014 to December 2016 on 3977 patients with type 2
      diabetes in Shanghai. KAP were evaluated using the modified Chinese version of
      the Diabetes, Hypertension and Hyperlipidemia (DHL) Knowledge Instrument,
      Diabetes Empowerment Scale-Short Form (DES-SF), and Summary of Diabetes Self-Care
      Activities (SDSCA). Clinical and biochemical measurements were performed at each
      sampling site. The association between KAP scores and achieving the combined
      target goal was assessed by multiple logistic regression. Patients having a
      higher score of knowledge were more likely to achieve the combined target goal.
      Furthermore, a turning point of knowledge score was found that the possibility of
      achieving the combined target goal presented a sharp increase when the knowledge
      score was more than 70. However, the scores of attitude and practices had no
      significant relations with achieving the combined target goal. Health
      intervention strategies, especially increasing integrated diabetes knowledge,
      should be targeted to patients with type 2 diabetes in communities.

PMID- 29464183
TI  - The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification
      of Diabetic Nephropathy Rats.
AB  - Background: This study explored the changes in expression of vascular smooth
      muscle cell (VSMC) markers and osteogenic markers, as well as the involvement of
      Notch1-RBP-Jk/Msx2 pathway in a rat model of diabetic nephropathy (DN) with
      vascular calcification. Methods: A rat model of DN with concomitant vascular
      calcification was created by intraperitoneal injection of streptozotocin followed
      by administration of vitamin D3 and nicotine. Biochemical analysis and
      histological examination of aortic tissue were performed. VSMC markers and
      osteogenic markers as well as target molecules in Notch1-RBP-Jk/Msx2 were
      determined by quantitative real-time polymerase chain reaction and
      immunohistochemical analysis. Results: Serum calcium and phosphorus levels were
      significantly increased in model rats as compared to that in normal controls.
      Diabetic rats with vascular calcification exhibited mineral deposits in aortic
      intima-media accompanied by decreased expression of VSMC markers and increased
      expression of osteogenic markers. Notch1, RBP-Jk, Msx2, Jagged1, and N1-ICD were
      barely expressed in the aortic wall of normal rats. In contrast, these were
      significantly increased in the model group at all time points (8, 12, and 16
      weeks), as compared to that in the normal rats. Conclusion: Activation of the
      Notch1-RBP-Jk/Msx2 signaling pathway may be involved in the development and
      progression of vascular calcification in DN.

PMID- 29464184
TI  - Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of
      Rats with Streptozotocin-Induced Diabetes.
AB  - Before this study, there had been no research evaluating the relationship between
      a lysosomal exoglycosidase profile and secretory function in the salivary glands
      of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats
      were divided into 4 groups of 8 animals each: control groups (C2, C4) and
      diabetic groups (STZ2, STZ4). The secretory function of salivary glands
      nonstimulated and stimulated salivary flow, alpha-amylase, total protein-and
      salivary exoglycosidase activities-N-acetyl-beta-hexosaminidase (HEX, HEX A, and
      HEX B), beta-glucuronidase, alpha-fucosidase, beta-galactosidase, and alpha
      mannosidase-was estimated both in the parotid and submandibular glands of STZ
      diabetic and control rats. The study has demonstrated that the activity of most
      salivary exoglycosidases is significantly higher in the parotid and submandibular
      glands of STZ-diabetic rats as compared to the healthy controls and that it
      increases as the disease progresses. Reduced secretory function of diabetic
      salivary glands was also observed. A significant inverse correlation between HEX
      B, alpha-amylase activity, and stimulated salivary flow in diabetic parotid gland
      has also been shown. Summarizing, STZ-induced diabetes leads to a change in the
      lysosomal exoglycosidase profile and reduced function of the salivary glands.

PMID- 29464185
TI  - Performance Characteristics of Different Anti-Double-Stranded DNA Antibody Assays
      in the Monitoring of Systemic Lupus Erythematosus.
AB  - Objective: We sought to evaluate different anti-double-stranded DNA assays for
      their performance characteristics in monitoring disease activity fluctuations in
      systemic lupus erythematosus (SLE). Methods: 36 active SLE patients were followed
      monthly. At each study visit (total n = 371), blood was collected and disease
      activity was scored using the SELENA-SLEDAI (excluding anti-dsDNA or complement
      components) and by a physician's global assessment (PGA). Four anti-dsDNA tests
      were compared. Linear mixed-effects models with random intercept and fixed slopes
      were used to evaluate the relationship between the longitudinal fluctuations of
      disease activity and anti-dsDNA titers. Results: At enrollment, positivity for
      QUANTA Lite and high-avidity anti-dsDNA assay was both 64% and significantly
      lower than anti-dsDNA positivity by QUANTA Flash (83%) and CLIFT (96%). Linear
      mixed-effects modeling indicated that the change in clinical SELENA-SLEDAI scores
      was associated with the titers of all anti-dsDNA with QUANTA Flash yielding the
      highest marginal R2 (0.15; p < 0.01). QUANTA Flash was the only anti-dsDNA assay
      significantly associated with the change in PGA (marginal R2 = 0.05; p < 0.01).
      Conclusion: These data indicate that anti-dsDNA antibodies determined by QUANTA
      Flash have a value in monitoring SLE disease activity.

PMID- 29464186
TI  - Exemestane Attenuates Hepatic Fibrosis in Rats by Inhibiting Activation of
      Hepatic Stellate Cells and Promoting the Secretion of Interleukin 10.
AB  - Exemestane (EXE) is an irreversible steroidal aromatase inhibitor mainly used as
      an adjuvant endocrine therapy for postmenopausal women suffering from breast
      cancer. Besides inhibiting aromatase activity, EXE has multiple biological
      functions, such as antiproliferation, anti-inflammatory, and antioxidant
      activities which are all involved in hepatic fibrosis. Therefore, we investigated
      the role of EXE during the progress of hepatic fibrosis. The effect of EXE on
      liver injury and fibrosis were assessed in two hepatic fibrosis rat models, which
      were induced by either carbon tetrachloride (CCl4) or bile duct ligation (BDL).
      The influence of EXE treatment on activation and proliferation of primary rat
      hepatic stellate cells (HSCs) was observed in vitro. The results showed that EXE
      attenuated the liver fibrosis by decreasing the collagen deposition and alpha-SMA
      expression in vivo and inhibited the activation and proliferation of primary rat
      HSCs in vitro. Additionally, EXE promoted the secretion of antifibrotic and anti
      inflammatory cytokine IL-10 in vivo and in HSC-T6 culture media. In conclusion,
      our findings reveal a new function of EXE on hepatic fibrosis and prompted its
      latent application in liver fibrotic-related disease.

PMID- 29464187
TI  - Nanoscale diffractive probing of strain dynamics in ultrafast transmission
      electron microscopy.
AB  - The control of optically driven high-frequency strain waves in nanostructured
      systems is an essential ingredient for the further development of nanophononics.
      However, broadly applicable experimental means to quantitatively map such
      structural distortion on their intrinsic ultrafast time and nanometer length
      scales are still lacking. Here, we introduce ultrafast convergent beam electron
      diffraction with a nanoscale probe beam for the quantitative retrieval of the
      time-dependent local deformation gradient tensor. We demonstrate its capabilities
      by investigating the ultrafast acoustic deformations close to the edge of a
      single-crystalline graphite membrane. Tracking the structural distortion with a
      28-nm/700-fs spatio-temporal resolution, we observe an acoustic membrane
      breathing mode with spatially modulated amplitude, governed by the optical near
      field structure at the membrane edge. Furthermore, an in-plane polarized acoustic
      shock wave is launched at the membrane edge, which triggers secondary acoustic
      shear waves with a pronounced spatio-temporal dependency. The experimental
      findings are compared to numerical acoustic wave simulations in the continuous
      medium limit, highlighting the importance of microscopic dissipation mechanisms
      and ballistic transport channels.

PMID- 29464188
TI  - Glycine receptor modulating antibody predicting treatable stiff-person spectrum
      disorders.
AB  - Background: Glycine receptor alpha-1 subunit (GlyRalpha1)-immunoglobulin G (IgG)
      is diagnostic of stiff-person syndrome (SPS) spectrum but has been reported
      detectable in other neurologic diseases for which significance is less certain.
      Methods: To assess GlyRalpha1-IgGs as biomarkers of SPS spectrum among patients
      and controls, specimens were tested using cell-based assays (binding [4 degrees
      C] and modulating [antigen endocytosing, 37 degrees C]). Medical records of
      seropositive patients were reviewed. Results: GlyRalpha1-IgG (binding antibody)
      was detected in 21 of 247 patients with suspected SPS spectrum (8.5%) and in 8 of
      190 healthy subject sera (4%) but not CSF. Among 21 seropositive patients, 20 had
      confirmed SPS spectrum clinically, but 1 was later determined to have a
      functional neurologic disorder. Sera from 9 patients with SPS spectrum , but not
      7 controls, nor the functional patient, caused GlyRalpha1 modulation (100%
      specificity). SPS spectrum phenotypes included progressive encephalomyelitis with
      rigidity and myoclonus (PERM) (8), classic SPS (5), stiff limb (5), stiff trunk
      (1), and isolated exaggerated startle (hyperekplexia, 1). Neuropsychiatric
      symptoms present in 12 patients (60%) were anxiety (11), depression (6), and
      delirium (3). Anxiety was particularly severe in 3 patients with PERM. Objective
      improvements in SPS neurologic symptoms were recorded in 16 of 18 patients who
      received first-line immunotherapy (89%, 9/10 treated with corticosteroids, 8/10
      treated with IVIg, 3/4 treated with plasma exchange, and 1 treated with
      rituximab). Treatment-sparing maintenance strategies were successful in 4 of 7
      patients (rituximab [2/3], azathioprine [1/1], and mycophenolate [1/3]).
      Conclusions: GlyRalpha1-modulating antibody improves diagnostic specificity for
      immunologically treatable SPS spectrum disorders. Classification of evidence:
      This study provides Class IV evidence that GlyRalpha1-modulating antibody
      accurately identifies patients with treatable SPS spectrum disorders.

PMID- 29464189
TI  - Achievements of Diabetes Goals and Their Determinants in Type 2 Diabetic Patients
      Attending Outpatient Diabetic Clinic in Northern Ethiopia.
AB  - Background: The aim of this study was to assess target diabetic goal achievements
      and to explore variables associated with them. Methods: A cross-sectional study
      was conducted between December 2015 and April 2016 on 188 type 2 diabetic
      patients attending Ayder Referral Hospital's outpatient diabetic clinic. Glycemic
      control was assessed using fasting plasma glucose values and total cholesterol
      and triglyceride were used to evaluate lipid profiles. Bivariate and multivariate
      logistic regression analyses were done to identify factors associated with poor
      glycemic control, hypertension, and dyslipidemia. Result: Mean duration of
      diabetes was 6.5 years. Combined glycemic, lipid, and blood pressure targets were
      achieved only in 8.5% of the participants. More males achieved combined targets
      than females. Separately, while above two-thirds of the patients had poor
      glycemic control (67%), more than half of the participants have had poor lipid
      (58.5%) and blood pressure (52.1%) control. A significant portion of the patients
      (68.1%) had also comorbidities other than hyperglycemia. In bivariate and
      multivariate analyses, longer duration of diabetes disease (AOR: 3.4; P = 0.013)
      and marked month to month fasting plasma glucose (FPG) variability as measured by
      large standard deviation (AOR: 2.5; P = 0.023) were significantly associated with
      overall poor mean FPG results. Female sex was also significantly associated with
      dyslipidemia (AOR: 1.9; P = 0.049). Conclusion: The study showed that
      achievements of combined diabetic goals are generally poor.

PMID- 29464190
TI  - Identification of Neurotensin Receptor Expressing Cells in the Ventral Tegmental
      Area across the Lifespan.
AB  - Neurotensin (Nts) promotes activation of dopamine (DA) neurons in the ventral
      tegmental area (VTA) via incompletely understood mechanisms. Nts can signal via
      the G protein-coupled Nts receptors 1 and 2 (NtsR1 and NtsR2), but the lack of
      methods to detect NtsR1- and NtsR2-expressing cells has limited mechanistic
      understanding of Nts action. To overcome this challenge, we generated dual
      recombinase mice that express FlpO-dependent Cre recombinase in NtsR1 or NtsR2
      cells. This strategy permitted temporal control over recombination, such that we
      could identify NtsR1- or NtsR2-expressing cells and determine whether their
      distributions differed between the developing and adult brain. Using this system,
      we found that NtsR1 is transiently expressed in nearly all DA neurons and in many
      non-DA neurons in the VTA during development. However, NtsR1 expression is more
      restricted within the adult brain, where only two thirds of VTA DA neurons
      expressed NtsR1. By contrast, NtsR2 expression remains constant throughout
      lifespan, but it is predominantly expressed within glia. Anterograde tract
      tracing revealed that NtsR1 is expressed by mesolimbic, not mesocortical DA
      neurons, suggesting that VTA NtsR1 neurons may represent a functionally unique
      subset of VTA DA neurons. Collectively, this work reveals a cellular mechanism by
      which Nts can directly engage NtsR1-expressing DA neurons to modify DA signaling.
      Going forward, the dual recombinase strategy developed here will be useful to
      selectively modulate NtsR1- and NtsR2-expressing cells and to parse their
      contributions to Nts-mediated behaviors.

PMID- 29464191
TI  - Impact of NMDA Receptor Overexpression on Cerebellar Purkinje Cell Activity and
      Motor Learning.
AB  - In many brain regions involved in learning NMDA receptors (NMDARs) act as
      coincidence detectors of pre- and postsynaptic activity, mediating Hebbian
      plasticity. Intriguingly, the parallel fiber (PF) to Purkinje cell (PC) input in
      the cerebellar cortex, which is critical for procedural learning, shows virtually
      no postsynaptic NMDARs. Why is this? Here, we address this question by generating
      and testing independent transgenic lines that overexpress NMDAR containing the
      type 2B subunit (NR2B) specifically in PCs. PCs of the mice that show larger NMDA
      mediated currents than controls at their PF input suffer from a blockage of long
      term potentiation (LTP) at their PF-PC synapses, while long-term depression (LTD)
      and baseline transmission are unaffected. Moreover, introducing NMDA-mediated
      currents affects cerebellar learning in that phase-reversal of the vestibulo
      ocular reflex (VOR) is impaired. Our results suggest that under physiological
      circumstances PC spines lack NMDARs postsynaptically at their PF input so as to
      allow LTP to contribute to motor learning.

PMID- 29464192
TI  - Specific Relationship between the Shape of the Readiness Potential, Subjective
      Decision Time, and Waiting Time Predicted by an Accumulator Model with Temporally
      Autocorrelated Input Noise.
AB  - Self-initiated movements are reliably preceded by a gradual buildup of neuronal
      activity known as the readiness potential (RP). Recent evidence suggests that the
      RP may reflect subthreshold stochastic fluctuations in neural activity that can
      be modeled as a process of accumulation to bound. One element of accumulator
      models that has been largely overlooked in the literature is the stochastic term,
      which is traditionally modeled as Gaussian white noise. While there may be
      practical reasons for this choice, we have long known that noise in neural
      systems is not white - it is long-term correlated with spectral density of the
      form 1/fbeta(with roughly 1 < beta < 3) across a broad range of spatial scales. I
      explored the behavior of a leaky stochastic accumulator when the noise over which
      it accumulates is temporally autocorrelated. I also allowed for the possibility
      that the RP, as measured at the scalp, might reflect the input to the accumulator
      (i.e., its stochastic noise component) rather than its output. These two premises
      led to two novel predictions that I empirically confirmed on behavioral and
      electroencephalography data from human subjects performing a self-initiated
      movement task. In addition to generating these two predictions, the model also
      suggested biologically plausible levels of autocorrelation, consistent with the
      degree of autocorrelation in our empirical data and in prior reports. These
      results expose new perspectives for accumulator models by suggesting that the
      spectral properties of the stochastic input should be allowed to vary, consistent
      with the nature of biological neural noise.

PMID- 29464193
TI  - Online LI-rTMS during a Visual Learning Task: Differential Impacts on Visual
      Circuit and Behavioral Plasticity in Adult Ephrin-A2A5-/- Mice.
AB  - Repetitive transcranial magnetic stimulation (rTMS) induces plasticity in normal
      and abnormal neural circuitries, an effect that may be influenced by intrinsic
      brain activity during treatment. Here, we study potential synergistic effects
      between low-intensity rTMS (LI-rTMS) and concurrent neural activity in promoting
      circuit reorganization and enhancing visual behavior. We used ephrin-A2A5-/-
      mice, which are known to possess visuotopic mapping errors that are ameliorated
      by LI-rTMS, and assessed the impact of stimulation when mice were engaged in a
      visual learning task. A detachable coil was affixed to each mouse, and animals
      underwent 2 wk of 10-min daily training in a two-choice visual discrimination
      task with concurrent LI-rTMS or sham stimulation. No-task controls (+LI
      rTMS/sham) were placed in the task arena without visual task training. At the end
      of the experiment, visuomotor tracking behavior was assessed, and corticotectal
      and geniculocortical pathway organization was mapped by injections of fluorescent
      tracers into the primary visual cortex. Consistent with previous results, LI-rTMS
      alone improved geniculocortical and corticotectal topography, but combining LI
      rTMS with the visual learning task prevented beneficial corticotectal
      reorganization and had no additional effect on geniculocortical topography or
      visuomotor tracking performance. Unexpectedly, there was a significant increase
      in the total number of trials completed by task + LI-rTMS mice in the visual
      learning task. Comparison with wild-type mice revealed that ephrin-A2A5-/- mice
      had reduced accuracy and response rates, suggesting a goal-directed behavioral
      deficit, which was improved by LI-rTMS. Our results suggest that concurrent brain
      activity during behavior interacts with LI-rTMS, altering behavior and different
      visual circuits in an abnormal system.

PMID- 29464194
TI  - Identification of Two Distinct Working Memory-Related Brain Networks in Healthy
      Young Adults.
AB  - Working memory (WM) is an important cognitive domain for everyday life
      functioning and is often disturbed in neuropsychiatric disorders. Functional
      magnetic resonance imaging (fMRI) studies in humans show that distributed brain
      areas typically described as fronto-parietal regions are implicated in WM tasks.
      Based on data from a large sample of healthy young adults (N = 1369), we applied
      independent component analysis (ICA) to the WM-fMRI signal and identified two
      distinct networks that were relevant for differences in individual WM task
      performance. A parietally-centered network was particularly relevant for
      individual differences in task measures related to WM performance ("WM
      dependent") and a frontally-centered network was relevant for differences in
      attention-dependent task performance. Importantly, frontal areas that are
      typically considered as key regions for WM were either involved in both WM
      dependent and attention-dependent performance, or in attention-dependent
      performance only. The networks identified here are provided as publicly available
      datasets. These networks can be applied in future studies to derive a low
      dimensional representation of the overall WM brain activation.

PMID- 29464195
TI  - Danger Changes the Way the Mammalian Brain Stores Information About Innocuous
      Events: A Study of Sensory Preconditioning in Rats.
AB  - The amygdala is a critical substrate for learning about cues that signal danger.
      Less is known about its role in processing innocuous or background information.
      The present study addressed this question using a sensory preconditioning
      protocol in male rats. In each experiment, rats were exposed to pairings of two
      innocuous stimuli in stage 1, S2 and S1, and then to pairings of S1 and shock in
      stage 2. As a consequence of this training, control rats displayed defensive
      reactions (freezing) when tested with both S2 and S1. The freezing to S2 is a
      product of two associations formed in training: an S2-S1 association in stage 1
      and an S1-shock association in stage 2. We examined the roles of two medial
      temporal lobe (MTL) structures in consolidation of the S2-S1 association: the
      perirhinal cortex (PRh) and basolateral complex of the amygdala (BLA). When the
      S2-S1 association formed in a safe context, its consolidation required neuronal
      activity in the PRh (but not BLA), including activation of AMPA receptors and
      MAPK signaling. In contrast, when the S2-S1 association formed in a dangerous
      context, or when the context was rendered dangerous immediately after the
      association had formed, its consolidation required neuronal activity in the BLA
      (but not PRh), including activation of AMPA receptors and MAPK signaling. These
      roles of the PRh and BLA show that danger changes the way the mammalian brain
      stores information about innocuous events. They are discussed with respect to
      danger-induced changes in stimulus processing.

PMID- 29464196
TI  - Sequences Flanking the Gephyrin-Binding Site of GlyRbeta Tune Receptor
      Stabilization at Synapses.
AB  - The efficacy of synaptic transmission is determined by the number of
      neurotransmitter receptors at synapses. Their recruitment depends upon the
      availability of postsynaptic scaffolding molecules that interact with specific
      binding sequences of the receptor. At inhibitory synapses, gephyrin is the major
      scaffold protein that mediates the accumulation of heteromeric glycine receptors
      (GlyRs) via the cytoplasmic loop in the beta-subunit (beta-loop). This binding
      involves high- and low-affinity interactions, but the molecular mechanism of this
      bimodal binding and its implication in GlyR stabilization at synapses remain
      unknown. We have approached this question using a combination of quantitative
      biochemical tools and high-density single molecule tracking in cultured rat
      spinal cord neurons. The high-affinity binding site could be identified and was
      shown to rely on the formation of a 310-helix C-terminal to the beta-loop core
      gephyrin-binding motif. This site plays a structural role in shaping the core
      motif and represents the major contributor to the synaptic confinement of GlyRs
      by gephyrin. The N-terminal flanking sequence promotes lower affinity
      interactions by occupying newly identified binding sites on gephyrin. Despite its
      low affinity, this binding site plays a modulatory role in tuning the mobility of
      the receptor. Together, the GlyR beta-loop sequences flanking the core-binding
      site differentially regulate the affinity of the receptor for gephyrin and its
      trapping at synapses. Our experimental approach thus bridges the gap between
      thermodynamic aspects of receptor-scaffold interactions and functional receptor
      stabilization at synapses in living cells.

PMID- 29464197
TI  - MeCP2 Deficiency Leads to Loss of Glial Kir4.1.
AB  - Rett syndrome (RTT) is an X-linked neurodevelopmental disorder usually caused by
      mutations in methyl-CpG-binding protein 2 (MeCP2). RTT is typified by apparently
      normal development until 6-18 mo of age, when motor and communicative skills
      regress and hand stereotypies, autonomic symptoms, and seizures present.
      Restoration of MeCP2 function selectively to astrocytes reversed several deficits
      in a murine model of RTT, but the mechanism of this rescue is unknown. Astrocytes
      carry out many essential functions required for normal brain functioning,
      including extracellular K+ buffering. Kir4.1, an inwardly rectifying K+ channel,
      is largely responsible for the channel-mediated K+ regulation by astrocytes. Loss
      of-function mutations in Kir4.1 in human patients result in a severe
      neurodevelopmental disorder termed EAST or SESAME syndrome. Here, we evaluated
      astrocytic Kir4.1 expression in a murine model of Rett syndrome. We demonstrate
      by chromatin immunoprecipitation analysis that Kir4.1 is a direct molecular
      target of MeCP2. Astrocytes from Mecp2-deficient mice express significantly less
      Kir4.1 mRNA and protein, which translates into a >50% deficiency in Ba2+
      sensitive Kir4.1-mediated currents, and impaired extracellular potassium
      dynamics. By examining astrocytes in isolation, we demonstrate that loss of
      Kir4.1 is cell autonomous. Assessment through postnatal development revealed that
      Kir4.1 expression in Mecp2-deficient animals never reaches adult, wild-type
      levels, consistent with a neurodevelopmental disorder. These are the first data
      implicating a direct MeCP2 molecular target in astrocytes and provide novel
      mechanistic insight explaining a potential mechanism by which astrocytic
      dysfunction may contribute to RTT.

PMID- 29464199
TI  - Immunosuppression Adherence in Stable Kidney Transplant Patients Converted From
      Immediate- to Prolonged-Release Tacrolimus in Clinical Practice: A Norwegian
      Study.
AB  - Background: This study investigated medication adherence in kidney transplant
      patients (KTPs) converted from immediate-release tacrolimus (IR-T) to prolonged
      release tacrolimus (PR-T)-based immunosuppression in routine practice. Methods:
      Noninterventional, observational, multicenter study in Norway. Included adult
      KTPs with stable graft function, converted from IR-T (baseline) to PR-T (1 mg:1
      mg) in routine practice. Data were collected at baseline, and months 1, 3, 6, and
      12 postconversion. Primary endpoint: adherence using the Basel Assessment of
      Adherence to Immunosuppressive Medication Scale. Secondary assessments:
      tacrolimus dose and trough levels (target, 3-7 ng/mL), clinical laboratory
      parameters (eg, estimated glomerular filtration rate [Modified Diet in Renal
      Disease]), and adverse events. Results: Ninety-one KTPs (mean +/- SD age 47.7 +/-
      14.3 years) were analyzed. Mean +/- SD change in PR-T dose from baseline (4.4 +/-
      2.4 mg/d) to month 12 was -0.1 +/- 0.9 mg/d; mean tacrolimus trough levels
      remained within target. Overall medication adherence increased from 45.6% at
      baseline to 58.1% at month 1, but was similar to baseline thereafter; taking and
      timing adherence followed a similar pattern. Odds ratio (OR) for adherence at
      month 1 (but not at other time points) was greater versus baseline for overall
      (OR, 1.71; P = 0.0205), taking (OR, 3.38; P = 0.0004), and timing (OR, 1.77, P =
      0.0252) dimensions. Mean +/- SD Basel Assessment of Adherence to
      Immunosuppressive Medication Scale visual analogue scale score at baseline was
      96.4 +/- 5.5%, and increased postconversion. Estimated glomerular filtration rate
      remained stable (month 12, 61.6 +/- 17.7 mL/min per 1.73 m2), as did other
      laboratory parameters. Two (2.2%) patients had adverse events considered
      probably/possibly treatment-related. Conclusions: There was disparity between
      high, patient-perceived and low, actual adherence. Converting stable KTPs from IR
      T to PR-T in routine practice did not impact long-term adherence to
      immunosuppression; renal function remained stable.

PMID- 29464198
TI  - Unraveling Synaptic GCaMP Signals: Differential Excitability and Clearance
      Mechanisms Underlying Distinct Ca2+ Dynamics in Tonic and Phasic Excitatory, and
      Aminergic Modulatory Motor Terminals in Drosophila.
AB  - GCaMP is an optogenetic Ca2+ sensor widely used for monitoring neuronal
      activities but the precise physiological implications of GCaMP signals remain to
      be further delineated among functionally distinct synapses. The Drosophila
      neuromuscular junction (NMJ), a powerful genetic system for studying synaptic
      function and plasticity, consists of tonic and phasic glutamatergic and
      modulatory aminergic motor terminals of distinct properties. We report a first
      simultaneous imaging and electric recording study to directly contrast the
      frequency characteristics of GCaMP signals of the three synapses for
      physiological implications. Different GCaMP variants were applied in genetic and
      pharmacological perturbation experiments to examine the Ca2+ influx and clearance
      processes underlying the GCaMP signal. Distinct mutational and drug effects on
      GCaMP signals indicate differential roles of Na+ and K+ channels, encoded by
      genes including paralytic (para), Shaker (Sh), Shab, and ether-a-go-go (eag), in
      excitability control of different motor terminals. Moreover, the Ca2+ handling
      properties reflected by the characteristic frequency dependence of the synaptic
      GCaMP signals were determined to a large extent by differential capacity of
      mitochondria-powered Ca2+ clearance mechanisms. Simultaneous focal recordings of
      synaptic activities further revealed that GCaMPs were ineffective in tracking the
      rapid dynamics of Ca2+ influx that triggers transmitter release, especially
      during low-frequency activities, but more adequately reflected cytosolic residual
      Ca2+ accumulation, a major factor governing activity-dependent synaptic
      plasticity. These results highlight the vast range of GCaMP response patterns in
      functionally distinct synaptic types and provide relevant information for
      establishing basic guidelines for the physiological interpretations of
      presynaptic GCaMP signals from in situ imaging studies.

PMID- 29464200
TI  - Polyomavirus BK Nephropathy-Associated Transcriptomic Signatures: A Critical
      Reevaluation.
AB  - Background: Recent work using DNA microarrays has suggested that genes related to
      DNA replication, RNA polymerase assembly, and pathogen recognition receptors can
      serve as surrogate tissue biomarkers for polyomavirus BK nephropathy (BKPyVN).
      Methods: We have examined this premise by looking for differential regulation of
      these genes using a different technology platform (RNA-seq) and an independent
      set 25 biopsies covering a wide spectrum of diagnoses. Results: RNA-seq could
      discriminate T cell-mediated rejection from other common lesions seen in formalin
      fixed biopsy material. However, overlapping RNA-seq signatures were found among
      all disease processes investigated. Specifically, genes previously reported as
      being specific for the diagnosis of BKPyVN were found to be significantly
      upregulated in T cell-mediated rejection, inflamed areas of fibrosis/tubular
      atrophy, as well as acute tubular injury. Conclusions: In conclusion, the search
      for virus specific molecular signatures is confounded by substantial overlap in
      pathogenetic mechanisms between BKPyVN and nonviral forms of allograft injury.
      Clinical heterogeneity, overlapping exposures, and different morphologic patterns
      and stage of disease are a source of substantial variability in "Omics"
      experiments. These variables should be better controlled in future biomarker
      studies on BKPyVN, T cell-mediated rejection, and other forms of allograft
      injury, before widespread implementation of these tests in the transplant clinic.

PMID- 29464201
TI  - Prediction of Early BK Virus Infection in Kidney Transplant Recipients by the
      Number of Cells With Intranuclear Inclusion Bodies (Decoy Cells).
AB  - Background: BK virus (BKV) is the cause of nephropathy. Because BKV nephropathy
      can progress to graft loss, early diagnosis of BKV infection is very important.
      In this study, we aimed to investigate the utility of quantifying cells with
      intranuclear inclusion bodies (decoy cells) in urinary sediment for the screening
      and monitoring of BKV infection in renal transplant recipients at our hospital.
      Methods: This was a retrospective single-center study. Urine sediment examination
      was performed at each outpatient visit, and the number of decoy cells was
      measured in the whole microscopic field. Patients (n = 41) were divided into the
      BK viremia group (blood positive for BKV DNA by polymerase chain reaction [PCR])
      and non-BK viremia group (blood negative for BKV DNA by PCR), and the decoy cell
      count in urinary sediments was examined. Results: The maximum decoy cell count
      was significantly higher (P = 0.04) in the BK viremia group than in the non-BK
      viremia group. In the receiver operating characteristic curve for the maximum
      decoy cells, the cutoff value was 507 cells. The area under the receiver
      operating characteristic curve was 0.8774 (95% confidence interval, 0.7739
      0.9810). The number of decoy cells at the time of appearance in the BK viremia
      group was not significantly different from that in the non-BK viremia group.
      However, the BK viremia group showed an increasing trend, whereas the non-BK
      viremia group showed a decreasing trend, in the number of decoy cells. There was
      a positive correlation between the number of decoy cells and the data from the
      urine BKV-DNA PCR quantification (correlation coefficient [r] = 0.74).
      Conclusions: Measurement of decoy cells in urinary sediments may predict early
      BKV infection, and if performed quickly, it may be useful for screening and
      continuous monitoring of BKV infection in renal transplant recipients.

PMID- 29464202
TI  - Prevalence and Clinical Correlates of Chronic Hepatitis E Infection in German
      Renal Transplant Recipients With Elevated Liver Enzymes.
AB  - Background: Elevated liver enzymes are frequently observed in renal transplant
      recipients and warrant further exploration. In immunosuppressed patients,
      hepatitis E virus (HEV) infection may cause chronic hepatitis, cirrhosis, and
      extrahepatic manifestations such as renal injury. Methods: We performed a
      retrospective cross-sectional study investigating the prevalence, clinical
      correlates, and outcome of chronic HEV infection in a cohort of renal transplant
      recipients with elevated liver enzymes. Results: Over a period of 30 months, 140
      of 1469 renal transplant recipients had elevated liver enzymes, of which serum
      samples from 98 patients were available to determine HEV status. Seventeen
      patients were detected with HEV infection, of which 16 developed chronic HEV
      infection, while 1 patient controlled viremia (prevalence of chronic infection of
      16.3%, with a minimum prevalence of 1.1% in the whole cohort). Increased liver
      stiffness was indicated by an average FibroScan result of 11.2 kPa in these
      patients. All 16 patients with chronic HEV infection were treated with ribavirin
      for a mean duration of 3 months. Five patients developed a viral rebound and
      received a second treatment course, of which 2 controlled HEV replication. Six
      months after the end of therapy, HEV clearance was achieved in 81.3% of the
      patients. One patient developed ribavirin resistance. Hemolytic anemia after
      ribavirin treatment was frequent, requiring blood transfusion in 3 patients. Four
      patients developed de novo glomerulonephritis, of which 2 were possibly
      associated with HEV infection. Conclusions: This retrospective study showed that
      prevalence of chronic HEV infection was high in our renal transplant patient
      cohort and was associated with significant liver impairment and the occurrence of
      renal injury. Ribavirin treatment was effective and should be initiated early to
      avoid complications, but the risk of severe hemolytic anemia makes strict
      monitoring essential.

PMID- 29464203
TI  - Rituximab Induction to Prevent the Recurrence of PSC After Liver Transplantation
      The Lessons Learned From ABO-Incompatible Living Donor Liver Transplantation.
AB  - Background: Multiple studies have failed to reveal an effective method for
      preventing the recurrence of primary sclerosing cholangitis (PSC) after liver
      transplantation (LTx). A national study conducted in Japan revealed several risk
      factors for the recurrence after living donor LTx (LDLTx); however, recipients of
      ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis.
      In the present study, we investigated the efficacy of an immunosuppressive
      protocol in ABO-I LTx on the recurrence of PSC after LDLTx. Methods: We conducted
      a national survey and analyzed the outcome of recipients who underwent ABO-I
      LDLTx for PSC (n = 12) between 1994 and 2010 in 9 centers and compared the
      outcome with that of ABO-compatible LDLTx for PSC (n = 96). The key elements of
      the immunosuppressive regimen in ABO-I LTx are plasma exchange sessions to remove
      existing antibodies, and the use of immunosuppression to control humoral
      immunity. Rituximab was added to the immunosuppression regimen from 2006 onward;
      5 patients received rituximab perioperatively. Results: All 7 recipients who
      underwent ABO-I LDLTx before 2006 (who did not receive rituximab) died of
      infection (n = 3), antibody-mediated rejection (n = 1), ABO-incompatibility
      associated cholangiopathy (n = 1) or recurrence of PSC (n = 2). In contrast, we
      found that all 5 recipients from 2006 (who were treated with rituximab) retained
      an excellent graft function for more than 7 years without any recurrence of PSC.
      Conclusions: The findings of this study shed light on the efficacy of a novel
      strategy to prevent the recurrence of PSC and the possible mechanisms provided by
      rituximab treatment are discussed.

PMID- 29464204
TI  - Tailored Rabbit Antithymocyte Globulin Induction Dosing for Kidney
      Transplantation.
AB  - Background: Rabbit antithymocyte globulin (rATG) is the most widely used kidney
      transplant induction immunotherapy in the United States. It was recently Food and
      Drug Administration approved for this indication with typical dose
      recommendations of 1.5 mg/kg for up to 7 days given via a central line. Methods:
      We theorized that reduced rATG dosing when compared with conventional dosing (6
      10.5 mg/kg) is safe and effective, leading to development of a risk-stratified
      treatment protocol. Five-year data from a retrospective cohort of 224 adult
      kidney transplants (2008-2013) with follow-up through 2015 is presented.
      Cumulative rATG doses of 3 mg/kg were administered peripherally to nonsensitized
      living donor recipients, 4.5 mg/kg to nonsensitized deceased donor recipients. A
      subset of higher immunologic risk recipients (defined as history of prior
      transplant, panel reactive antibody greater than 20%, or flow cytometry
      crossmatch positivity) received 6 mg/kg. Results: There were no differences in
      patient or graft survival between the 3 groups. One-year rejection rates in the
      first 2 groups were 8.3% and 8.8%, respectively, comparable to contemporaneous
      rates reported to the Scientific Registry of Transplant Recipients. Dose
      tailoring permitted substantial cost savings estimated at US $1 091 502. Mean
      length of stay fell by almost 3 days as the protocol was refined. There were no
      episodes of phlebitis. Infection rates were comparable with those reported to the
      Scientific Registry of Transplant Recipients. Conclusions: The novel findings of
      the current study include peripheral administration, reduced dosing, favorable
      safety, excellent allograft outcomes, and clear associative data regarding
      reduced costs and length of stay.

PMID- 29464205
TI  - Pilot Study of Delayed ICOS/ICOS-L Blockade With alphaCD40 to Modulate Pathogenic
      Alloimmunity in a Primate Cardiac Allograft Model.
AB  - Background: Inducible costimulator (ICOS) is rapidly upregulated with T-cell
      stimulation and may represent an escape pathway for T-cell costimulation in the
      setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no
      efficacy in a primate renal allograft model, but rodent transplant models suggest
      that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival
      and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to
      anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or
      attenuates pathogenic alloimmunity. Methods: Cynomolgus monkey heterotopic
      cardiac allograft recipients were treated with alphaCD40 (2C10R4, d0-90) either
      alone or with the addition of delayed ICOS-Ig (d63-110). Results: Median
      allograft survival was similar between ICOS-Ig + alphaCD40 (120 days, 120-125
      days) and alphaCD40 (124 days, 89-178 days) treated animals, and delayed ICOS-Ig
      treatment did not prevent allograft rejection in animals with complete CD40
      receptor coverage. Although CD4+ TEM cells were decreased in peripheral blood
      (115 +/- 24) and mLNs (49 +/- 1.9%) during ICOS-Ig treatment compared with
      monotherapy (214 +/- 27%, P = 0.01; 72 +/- 9.9%, P = 0.01, respectively), acute
      and chronic rejection scores and kinetics of alloAb elaboration were similar
      between groups. Conclusions: Delayed ICOS-Ig treatment with the reagent tested is
      probably ineffective in modulating pathogenic primate alloimmunity in this model.

PMID- 29464206
TI  - Improved Cuff Technique and Intraoperative Detection of Vascular Complications
      for Hind Limb Transplantation in Mice.
AB  - Background: Vascularized composite tissue allotransplantation (VCA) from a
      cadaveric donor has now become a clinical reality and the treatment modality of
      choice for patients with devastating injuries, deformities, and complex tissue
      defects. However, many VCA patients experience severe toxicities due to the
      strong immunosuppression required secondary to high antigenicity of the grafts.
      To improve immunosuppressive protocols for VCA, feasible and reliable preclinical
      models are necessary. The purpose of this study was to introduce new techniques
      to an established preclinical VCA model to accelerate future investigations.
      Methods: C57BL/6 (H-2b) and BALB/c (H-2d) mice were used to perform VCA as
      recipients and donors, respectively. Surgery time, success rate, associated
      complications, and mortality were analyzed. Blood flow in grafts was interrogated
      with laser speckle image (LSI). Results: A nonsuture cuff technique was used with
      the abdominal aorta for end-to-end anastomosis. The cuff technique demonstrated
      efficiency for donor surgery (52 +/- 10 minutes for donor vs. 45 +/- 8 minutes
      for recipient surgery). Successful revascularization was achieved in 27 (90%) of
      30 transplants. The majority of surgical complications occurred within 48 hours
      including artery occlusion, venous occlusion, cerebral stroke, and minor bleeding
      without mortality. LSI was useful in detecting intraoperative vascular
      complications with display patterns predictive of complication type. Conclusions:
      The described techniques may facilitate a more efficient heterotopic hind limb
      transplantation mouse model of VCA.

PMID- 29464207
TI  - Socioeconomic Inequalities in the Kidney Transplantation Process: A Registry
      Based Study in Sweden.
AB  - Background: Few studies have examined the association between individual-level
      socioeconomic status and access to kidney transplantation. This study aims to
      investigate the association between predialysis income and education, and access
      to (i) the kidney waitlist (first listing), and (ii) kidney transplantation
      conditional on waitlist placement. Adjustment will be made for a number of
      medical and nonmedical factors. Methods: The Swedish Renal Register was linked to
      national registers for adult patients in Sweden who started dialysis during 1995
      to 2013. We employed Cox proportional hazards models. Results: Nineteen per cent
      of patients were placed on the waitlist. Once on the waitlist, 80% received
      kidney transplantation. After adjusting for covariates, patients in the highest
      income quintile were found to have higher access to both the waitlist (hazard
      ratio [HR], 1.73; 95% confidence interval [CI], 1.53-1.96) and kidney
      transplantation (HR, 1.33; 95% CI, 1.16-1.53) compared with patients in the
      lowest income quintile. Patients with higher education also had better access to
      the waitlist and kidney transplantation (HR, 2.16; 95% CI, 1.94-2.40; and HR,
      1.16; 95% CI, 1.03-1.30, respectively) compared with patients with mandatory
      education. Conclusions: Socioeconomic status-related inequalities exist with
      regard to both access to the waitlist, and kidney transplantation conditional on
      listing. However, the former inequality is substantially larger and is therefore
      expected to contribute more to societal inequalities. Further studies are needed
      to explore the potential mechanisms and strategies to reduce these inequalities.

PMID- 29464208
TI  - Multi-heme cytochromes provide a pathway for survival in energy-limited
      environments.
AB  - Bacterial reduction of oxidized sulfur species (OSS) is critical for energy
      production in anaerobic marine subsurfaces. In organic-poor sediments, H2 has
      been considered as a major energy source for bacterial respiration. We identified
      outer-membrane cytochromes (OMCs) that are broadly conserved in sediment OSS
      respiring bacteria and enable cells to directly use electrons from insoluble
      minerals via extracellular electron transport. Biochemical, transcriptomic, and
      microscopic analyses revealed that the identified OMCs were highly expressed on
      the surface of cells and nanofilaments in response to electron donor limitation.
      This electron uptake mechanism provides sufficient but minimum energy to drive
      the reduction of sulfate and other OSS. These results suggest a widespread
      mechanism for survival of OSS-respiring bacteria via electron uptake from solid
      minerals in energy-poor marine sediments.

PMID- 29464209
TI  - Survival of spin state in magnetic porphyrins contacted by graphene nanoribbons.
AB  - We report on the construction and magnetic characterization of a fully functional
      hybrid molecular system composed of a single magnetic porphyrin molecule bonded
      to graphene nanoribbons with atomically precise contacts. We use on-surface
      synthesis to direct the hybrid creation by combining two molecular precursors on
      a gold surface. High-resolution imaging with a scanning tunneling microscope
      finds that the porphyrin core fuses into the graphene nanoribbons through the
      formation of new carbon rings at chemically predefined positions. These ensure
      the stability of the hybrid and the extension of the conjugated character of the
      ribbon into the molecule. By means of inelastic tunneling spectroscopy, we prove
      the survival of the magnetic functionality of the contacted porphyrin. The
      molecular spin appears unaffected by the graphenoid electrodes, and we simply
      observe that the magnetic anisotropy appears modified depending on the precise
      structure of the contacts.

PMID- 29464210
TI  - Topological transport of sound mediated by spin-redirection geometric phase.
AB  - When a dynamic system undergoes a cyclic evolution, a geometric phase that
      depends only on the path traversed in parameter space can arise in addition to
      the normal dynamical phase. These geometric phases have profound impacts in both
      quantum and classical physics. In addition to the geometric phase associated with
      band structures in reciprocal space that has led to the discovery of topological
      insulators, the spin-redirection geometric phase induced by the SO(3) rotation of
      states in real space can also give rise to intriguing phenomena such as the
      photonic analog of the spin Hall effect. By exploiting the orbital angular
      momentum of sound vortices, we theoretically and experimentally demonstrate the
      spin-redirection geometric phase effects in airborne sound, which is a scalar
      wave without spin. We show that these effects, associated with the helical
      transport of sound, can be used to control the flow of sound. This finding opens
      new possibilities for the manipulation of scalar wave propagation by exploiting
      spin-redirection geometric phases.

PMID- 29464211
TI  - Probing quantum coherence in single-atom electron spin resonance.
AB  - Spin resonance of individual spin centers allows applications ranging from
      quantum information technology to atomic-scale magnetometry. To protect the
      quantum properties of a spin, control over its local environment, including
      energy relaxation and decoherence processes, is crucial. However, in most
      existing architectures, the environment remains fixed by the crystal structure
      and electrical contacts. Recently, spin-polarized scanning tunneling microscopy
      (STM), in combination with electron spin resonance (ESR), allowed the study of
      single adatoms and inter-atomic coupling with an unprecedented combination of
      spatial and energy resolution. We elucidate and control the interplay of an Fe
      single spin with its atomic-scale environment by precisely tuning the phase
      coherence time T2 using the STM tip as a variable electrode. We find that the
      decoherence rate is the sum of two main contributions. The first scales linearly
      with tunnel current and shows that, on average, every tunneling electron causes
      one dephasing event. The second, effective even without current, arises from
      thermally activated spin-flip processes of tip spins. Understanding these
      interactions allows us to maximize T2 and improve the energy resolution. It also
      allows us to maximize the amplitude of the ESR signal, which supports
      measurements even at elevated temperatures as high as 4 K. Thus, ESR-STM allows
      control of quantum coherence in individual, electrically accessible spins.

PMID- 29464212
TI  - Understanding the informational needs of patients with IPF and their caregivers:
      'You get diagnosed, and you ask this question right away, what does this mean?'
AB  - Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, incurable lung
      disease whose intrusive symptoms rob patients of their quality of life. Patients
      with IPF rely on their caregivers for support and assistance in amounts that vary
      according to patients' individual circumstances and disease severity.
      Knowledgeable and well-informed patients and caregivers are best suited to deal
      with life-altering conditions like IPF. Methods: We conducted two hour-long focus
      groups with 13 patients with IPF and 4 caregivers of patients with IPF to better
      understand their informational needs and in what format such information should
      be delivered. Results: Patients discussed the challenges IPF creates in their
      daily lives. They wanted information on how to live well despite having IPF,
      practical information on how they could remain active and travel and how they
      could preserve their quality of life despite living with a life-threatening
      disease like IPF. Caregivers wanted information on the general aspects of IPF,
      because it would help them understand what patients were going through. They also
      wanted specific information on how to give care to a patient with IPF, even when
      physical care may not be needed (as in earlier phases of the disease). Patients
      and caregivers both needed efficient information delivery from trustworthy
      sources, including the healthcare team involved in their care. They considered
      both spoken and written information valuable, and ease of access was critical.
      Conclusion: This study provides valuable insight regarding the informational
      needs of IPF patients and their caregivers. It is hoped that identifying or
      creating sources of this information, and insuring that patients and caregivers
      have access to it, will improve well-being for patients with IPF and their
      caregivers.

PMID- 29464213
TI  - Effect of initial lactate level on short-term survival in patients with out-of
      hospital cardiac arrest.
AB  - Purpose: This study evaluated whether serum lactate levels (SLL) at admission in
      patients with cardiac arrest (CA) can predict successful return of spontaneous
      circulation (ROSC) or short-term survival, especially within the first 24 h.
      Materials and methods: This prospective, observational study was conducted in the
      emergency department (ED) of a training and research hospital from April 2015
      through February 2016. It included all patients older than 18 years who presented
      to the ED during the study period with non-traumatic out-of-hospital cardiac
      arrest (OHCA). The study measured two outcomes: whether ROSC was achieved and
      whether short-term survival was achieved. ROSC was defined as the presence of
      spontaneous circulation for the first hour after cardiopulmonary resuscitation
      (CPR). Survival was defined as having survived for a minimum of 24 h after ROSC.
      Results: The study included 140 patients who were admitted to the ED with OHCA.
      ROSC was achieved in 55 patients (39.3%), and survival for 24 h following CA was
      achieved in 42 patients (30%). The mean SLL in the ROSC (+) and ROSC (-) groups
      were 9.1 +/- 3.2 mmol/L and 9.8 +/- 2.9 mmol/L, respectively. The mean SLL in the
      survivor and non-survivor groups were 8.6 +/- 2.9 mmol/L and 10 +/- 3.1 mmol/L,
      respectively. These differences were not statistically significant (p = 0.1). A
      multivariate regression model assessing the factors that predicted both ROSC and
      24-h survival showed the odds ratio (OR) of initial SLL was 1.3 (95% CI: 1.05
      1.6) and 1.1 (95% CI: 0.9-1.3), respectively. Conclusions: This study showed that
      in OHCA patients, SLL on admission was not associated with increased ROSC
      achievement or 24-h survival.

PMID- 29464214
TI  - The diagnostic value of complete blood count parameters in patients with
      subarachnoid hemorrhage.
AB  - Objectives: Diagnosis of subarachnoid hemorrhage (SAH) in patients presenting
      with headache is challenging and there has been any biomarker studied for
      excluding of SAH in those patients. We aim to determine the sensitivity of
      leukocytosis or left shift to exclude the diagnosis of SAH in ED patients
      presenting with headache. Method: Adult patients with headache who received a
      computed tomography (CT) with the diagnosis of SAH and had a complete blood count
      (CBC) represent the case group, headache patients with normal CT and had a CBC
      represent the control group. The white blood cell (WBC) count and percentage of
      polymorphonuclear cells (PMNs%) taken during admission and within the first 6 and
      12 h of admission were recorded. Results: A hundred ninety seven patients with
      SAH and 197 patients without SAH were enrolled in to study. Sensitivity,
      specificity, NPV and PPV of leukocytosis or increase in PMNs% (left shift) in the
      diagnosis of SAH was 89.8% (84.5-93.5, 95% CI), 46.7% (39.6-53.9, 95% CI), 82.1%
      (73.5-88.4, 95% CI) and 62.8% (56.8-68.4, 95% CI) respectively on initial
      emergency department (ED) admission. Conclusion: CBC should be considered as a
      noninvasive test for the exclusion of SAH in ED patients with 6 h observation.

PMID- 29464215
TI  - Accuracy of point-of-care ultrasound using low frequency curvilinear transducer
      in the diagnosis of shoulder dislocation and confirmation of appropriate
      reduction.
AB  - Background: Ultrasound (US) is an effective modality in the evaluation of
      shoulder dislocation and reduction. In most studies, high frequency US probes
      have been used. Objective: To determine the sensitivity and specificity of low
      frequency US in the diagnosis of shoulder dislocation and its proper reduction in
      the emergency department (ED). Methods: In a prospective observational study 84
      patients, suspicious of shoulder dislocation, were enrolled in our study. In ED,
      they all underwent low frequency (curve) probe US examination by the emergency
      physician at the time of admission. Standard radiographies of their shoulder
      joints were taken later and then reported by the attending radiologist. As soon
      as the shoulder dislocation was confirmed, reduction of the joint was done under
      procedural sedation and analgesia. US and radiography of the relocated joint were
      taken for the second time. The sensitivity and specificity of low frequency US
      were compared with radiography by the appropriate statistical analysis. Results:
      In comparison to radiography, US had a sensitivity of 100.0%, specificity of
      80.0%, positive predictive value of 98.7%, and negative predictive value of
      100.0% in diagnosis of shoulder dislocation. The specificity of US in diagnosis
      of proper reduction of the joint, was estimated to be 98.7% with a negative
      predictive value of 100.0%. US took a significantly less time than radiography to
      be performed (p < 0.001). Conclusions: Low frequency US is highly accurate in
      diagnosing shoulder dislocation and its proper reduction. Thus it might be a good
      substitute for radiography in these situations.

PMID- 29464216
TI  - Demographic and clinical characteristics among Turkish homeless patients
      presenting to the emergency department.
AB  - Objective: Since the homeless are at greater risk of encountering health problems
      than the general population, the reasons for and incidence of their presentations
      to emergency departments also vary. The purpose of this study was to determine
      the sociodemographic and clinical characteristics of Turkish homeless patients
      who brought to the emergency department by ambulance. Materials and methods: The
      records of homeless adult patients brought to the ED by 112 emergency service
      ambulance teams over a 1-year period from January to December, 2014, were
      examined retrospectively. Results: Thirty-six (21.56%) of the homeless patients
      enrolled in the study presented due to trauma, and 131 (78.44%) due to non
      traumatic causes. One hundred thirty-seven (82.04%) of the total patient group
      were male. The mean age of the non-trauma patients was 47.3 +/- 15.2 years
      (range, 18-81 years), and the mean age of the trauma patients was 36.9 +/- 14.4
      years (range, 18-63 years). The most common reason for presentation among
      patients presenting to the emergency department for non-trauma reasons was
      clouded consciousness (n = 39, 23.35%), followed by general impaired condition (n
      = 26, 15.57%), respiratory difficulty (n = 25 14.97%) and abdominal pain (n = 21,
      12.57%). The most common reason for presentation among trauma cases was traffic
      accidents (n = 13, 7.78%), followed by sharp implement injury (n = 9, 5.39%).
      Four (2.4%) homeless patients died in the emergency department, three (%1.8)
      homeless patients discharged from the emergency department, and the remaining 160
      (95.8%) were admitted to the hospital. Conclusion: Homeless patients may present
      to the emergency department due to traumatic or non-traumatic causes. Admission
      levels are high among these patients, who may have many acute and chronic
      problems, and appropriate precautions must be taken in the management of these
      subjects in the emergency department.

PMID- 29464218
TI  - A ventricular septal defect restricted by the tricuspid septal leaflet and
      discrete subaortic membrane presenting with high-grade atrioventricular block and
      syncope.

PMID- 29464217
TI  - A retrospective analysis of cases with neuroleptic malignant syndrome and an
      evaluation of risk factors for mortality.
AB  - Objective: Neuroleptic malignant syndrome (NMS) is a neurological emergency
      rarely encountered in clinical practice but with a high mortality rate. Cases
      associated with atypical antipsychotic use or termination of dopamine agonists
      have been seen in recent years. The purpose of this study was to assess the
      presence of risk factors for mortality by investigating all clinical and
      laboratory characteristics of cases with NMS. Material and methods: This
      descriptive, cross-sectional study retrospectively investigated all clinical and
      laboratory characteristics by scanning the ICD-10 codes of patients presenting to
      the XXXX Faculty of Medicine Emergency Department and diagnosed with NMS between
      2006 and 2016. Patients were divided into surviving and non-surviving groups, and
      the data elicited were subjected to statistical comparisons. Results: The mean
      age of the 18 patients diagnosed with NMS was 46.9 +/- 4.8 years, and 50% were
      women. In addition to antipsychotics among the drugs leading to NMS, the syndrome
      also developed as a result of levodopa withdrawal in three patients and
      metoclopramide use in one patient. Statistically significant differences were
      determined between the surviving and non-surviving patients in terms of blood
      pressure, blood urea nitrogen (BUN), creatine kinase (CK) and mean platelet
      volume (MPV) values (p <= 0.05). Conclusion: In this study the most common agent
      that cause NMS was atypical antipsychotics. Also advanced age, increased blood
      pressure and serum CK, BUN and MPV values were identified as potential risk
      factors for mortality in NMS.

PMID- 29464219
TI  - Typical pericarditis ECG findings after falling from height. The PR segment
      depression or ST segment elevation?
AB  - Acute pericarditis (AP) following blunt thoracic trauma is rare and difficult to
      diagnosis. A 43-year-old man with offered to the emergency department (ED) after
      falling from height before a week ago. The ECG performed in the ED was abnormal,
      ECG revealed PR segment depression in leads DII, DIII, aVF, and V3-6 and a
      preliminary diagnosis of acute inferolateral STEMI was presumed. Patients have
      evidence of systemic inflammation, including leukocytosis, elevated erythrocyte
      sedimentation rate. We are reporting a case of post-traumatic acute pericarditis
      presenting with PR-segment depression and normal cardiac enzymes mimicking acute
      STEMI.

PMID- 29464220
TI  - A rare cause of acute abdomen in the ED: Chemotherapy-induced pneumatosis
      intestinalis.
AB  - Pneumatosis intestinalis (PI) and portomesenteric venous gas (PVG) refers to the
      presence of air within the intestinal wall and portomesenteric vessels. Most of
      the time, it is associated with mesenteric ischemia that requires immediate
      surgical intervention as it has high mortality rate. It may also be seen
      secondary to various conditions, including infections, surgeries, and some
      chemotherapeutic drugs. A 61-year old-male was admitted to our emergency
      department complaining of abdominal pain after chemotherapy. Radiological
      evaluation of the patient demonstrated massive PVG and PI. Patient underwent
      urgent surgery due to the possibility of intestinal ischemia and infarction, but
      no necrosis was identified Chemotherapeutic drug-induced PI and PVG was the final
      diagnosis. Although PI and PVG are signs of mesenteric ischemia and intestinal
      necrosis most the of time, chemotherapeutic drugs may also cause PI and PVG
      rarely. Recent history of chemotheraphy and absence of any mesenteric vascular
      occlusion may be the diagnostic clue.

PMID- 29464221
TI  - A young puerperal woman presenting to emergency department with severe dyspnea.
AB  - Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with
      heart failure (HF) secondary to left ventricular systolic dysfunction towards the
      end of pregnancy or in the months following delivery, where no other cause of HF
      is found. The symptoms and signs of this rare disorder mimic those of the
      physiological changes of pregnancy or other cardiovascular diseases.
      Consequently, its diagnosis is frequently delayed, which worsens an already poor
      prognosis. Here, we report a young adult who was diagnosed with PPCM, early, with
      the help of focused cardiac ultrasonography, performed after presenting to the
      emergency department with nonspecific respiratory complaints, including dyspnea
      and hemoptysis, which suggested at first pulmonary embolism.

PMID- 29464222
TI  - Nivolumab, a new immunomodulatory drug, a new adverse effect; adrenal crisis.
AB  - Owing to the advancements in medicine, new information is obtained regarding
      cancer, new antineoplastic agents are developed. Frequent use of these new
      pharmacological agents emergency physicians to be vigilant about their side
      effects. We present a case of adrenal crisis in a patient with non-small cell
      lung cancer (NSCLC), caused by an immunomodulatory drug; nivolumab. While adverse
      events are related to other immunomodulatory drugs have been reported in
      literature, our case is the first nivolumab-related adrenal failure to be
      reported. A patient with lung cancer presented to the emergency room(ER) with
      nausea and vomiting. Hyponatremia, hyperkalemia, persistent hypoglycemia led to
      the diagnosis of adrenal crisis. Having direct effect on the immune system, these
      drugs were claimed to be highly reliable. However, there is no reliable data on
      the side effect profile of these agents. It should be kept in mind that life
      threatening auto-immune reactions may occur.

PMID- 29464224
TI  - Acne in adolescents.
AB  - BACKGROUND: Acne vulgaris affects more than 90% of Australian adolescents aged 16
      18 years. It may have a significantly deleterious effect on their self-esteem and
      emotional state. Moderate-to-severe acne can lead to scarring. There are many
      treatment options available. Most teenagers obtain information from their peers
      or from the internet. OBJECTIVE: The aim of this article is to inform general
      practitioners (GPs) of the pathogenesis, physiology and description of acne, as
      well as therapeutic options, including topical and systemic therapies. Skin care,
      diet and other factors of importance are also discussed. DISCUSSION: The first
      point of contact with patients is in general practice. GPs effectively manage
      most patients with acne. Treatment choice is guided by experience, with many
      clinical acne treatment guidelines available. The most common reason for
      treatment failure is insufficient duration of therapy. Successful treatments
      require months of topical agents and, in many cases, additional systemic
      therapies. Internationally, there is a resurgence in the basic research of acne
      vulgaris, leading to new topical and systemic treatments.

PMID- 29464223
TI  - Determinants of inappropriate acute pain management in old people unable to
      communicate verbally in the emergency department.
AB  - Objectives: Poor pain management is relevant among individuals unable to
      communicate verbally (UCV). Analgesia may be due to three determinants: patients'
      status, physician's characteristics and pain etiology. Our aim is to investigate
      the association between prescription of ED pain treatment and these determinants.
      Materials and Methods: An observational prospective study including UCV patients
      was conducted. Severity of pain was evaluated by ALGOPLUS Scale and a score P >=
      2 out of 5 on the pain scale was retained as the threshold for the presence of
      acute pain in elderly UCV patients. Results: Our data showed that only 31,9% of
      UCV patients received a pharmacological treatment. The presence of the caregiver
      would influence the rate of therapy administration [OR 6,19 (95% CI 2,6-14,75)].
      The presence of leg pain [OR 0,32 (95% CI 0,12-0,86)] and head pain [OR 0,29 (95%
      CI 0,10-0,84)] were less likely associated to receive analgesia. Pain related to
      trauma [OR 4.82 (95% CI 1.17 to 19.78)] and youngest physicians [OR 1.08 (95% CI
      1.001 to 1.18)] were variables associated with the administration of drugs
      opiates. Discussion: Older UCV patients presenting to the ED with pain are at
      high risk of inadequate analgesia. Providers should always suspect presence of
      pain and an increasing need for behavioural pain evaluation is necessary for a
      complete assessment. Conclusions: Presence of a caregiver influences a more
      appropriate pain management in these patients. Staff training on pain management
      could result in better assessment, treatment, and interaction with caregivers.

PMID- 29464225
TI  - Eczema management in school-aged children.
AB  - BACKGROUND: Atopic eczema is a relapsing inflammatory skin condition that can be
      lifelong. Management of eczema is often focused on infants, with many school-aged
      children undertreated. Uncontrolled eczema has a significant impact on the
      quality of life of the child and their family. OBJECTIVE: The objective of this
      article is to discuss the practical management of eczema in school-aged children.
      DISCUSSION: This article will describe how eczema manifests in school-aged
      children, focusing on when to suspect triggers and how to manage these from a
      general practice perspective, and when to refer the child on to specialist
      services.

PMID- 29464226
TI  - Depression in children.
AB  - BACKGROUND: Major depressive disorder (MDD) in children (5-12 years of age) is a
      confronting and serious psychiatric illness. MDD has significant ramifications
      for the psychosocial development of the child, yet it remains under-recognised
      and undertreated. General practice is where these children and their parents will
      first present. OBJECTIVE: The aim of this article is to provide general
      practitioners (GPs) with a framework for considering MDD in a child and
      recommendations for treatment. DISCUSSION: Children with MDD have the same core
      features as adolescents and adults, taking into account the child's capacities
      for cognition and language, and developmental stage. Earlier onset of illness is
      associated with poorer outcomes and greater psychiatric morbidity persisting into
      adulthood. MDD is more common than anticipated, and should be considered for any
      child presenting with depressive symptoms and/or impaired psychosocial
      functioning. Despite limited evidence, numerous interventions exist that will,
      ideally, significantly affect the child's developmental trajectory. GPs are in an
      important position to initiate these interventions.

PMID- 29464227
TI  - Childhood constipation.
AB  - BACKGROUND: Constipation is best defined as difficulty passing stools that may be
      infrequent (<=2 per week), painful and associated with stool retention. Childhood
      constipation is common, with a prevalence of 3-30% worldwide. Most constipation
      in children is functional and related to behavioural withholding after an
      unpleasant stool event. Successful diagnosis and management can occur in primary
      care, and specialist referral is only needed for refractory cases or concerns
      regarding organic pathology. OBJECTIVE: This article aims to provide a structure
      for evaluating, diagnosing and managing childhood functional constipation in
      general practice. DISCUSSION: Structured history and examination can screen for
      organic pathology or red flags that require specialist referral. Investigations
      such as abdominal X-ray are not routine. Early management of childhood
      constipation provides improved quality of life for patients and their families.
      Management, including disimpaction and maintenance, should maintain continuity of
      care and provide long-term support for families.

PMID- 29464228
TI  - Growth disorders in adolescents.
AB  - BACKGROUND: Growth is one of the fundamental processes of adolescent development.
      Careful history and examination, and relevant tar-geted investigations, can
      streamline the referral process, highlighting the important role of primary
      healthcare clinicians. OBJECTIVE: This article will provide a guide for
      clinicians to categorise growth patterns in adolescents, and recognise patients
      who may have a growth disorder. It will assist clinicians in considering
      appropriate investigations, and provide guidance for when to refer the adolescent
      to appropriate paediatric specialists. DISCUSSION: Causes of tall and short
      stature can often be distinguished on history, physical examination, and accurate
      pubertal staging. The height of the adolescent should always be considered in the
      context of their genetic potential. Physiological variants re-main the most
      common reason for short stature, but awareness of the features of pathological
      causes is critical. One of the most common presentations is maturational delay in
      males, and an approach to this issue is discussed.

PMID- 29464229
TI  - Management of bariatric patients beyond the scalpel.
AB  - BACKGROUND: Obesity management in general practice sometimes involves referral of
      patients for bariatric surgery. Integral to the success of long-term weight loss
      maintenance is supporting the patient's psychological, nutritional and exercise
      needs. OBJECTIVE: This article is written to equip general practitioners (GPs) to
      manage the comprehensive needs, before and after bariatric surgery, of patients
      who are obese. DISCUSSION: The number of patients undergoing bariatric surgery in
      Australia has increased significantly in the past few years. Pre-operative and
      postoperative management of this intervention presents a challenge for GPs. In
      this article we provide guidance around psychological, nutritional and exercise
      interventions, to equip GPs in managing patients who are obese. Access to allied
      health providers is not always available for patients, so this article is co
      written with allied health colleagues who share their expertise as a resource for
      GPs.

PMID- 29464230
TI  - The Australian Mid-West Coastal Marine Wound Infections Study.
AB  - BACKGROUND: Marine organism wound infections are common in coastal regions of
      Western Australia. Local treatment guidelines are based on studies from
      elsewhere. The objective of this article was to identify the causative organisms
      in marine wounds sustained in the subtropical and tropical coastal waters of the
      Indian Ocean, Gascoyne region (north-west), Western Australia. METHODS: This was
      a prospective study. A single wound swab was taken from 28 consenting patients
      who presented with a suppurating marine wound to the emergency departments of
      Carnarvon and Exmouth hospitals. RESULTS: The wounds of 27 out of 28 patients
      returned a positive culture. The two most common organisms were Staphylococcus
      aureus (n = 18/28; 64.3%) and Vibrio species (n = 9/28; 32.1%). The culture was
      polymicrobial in 11 patients (39.3%). DISCUSSION: S. aureus or Vibrio species
      were frequently seen in marine wounds, and infections were often polymicrobial.
      Our results suggest that flucloxacillin (or clindamycin) and doxycycline (or
      ciprofloxacin) would be a reasonable combination for empirical oral therapy in
      adults.

PMID- 29464231
TI  - A mixed-methods feasibility study of routinely weighing patients in general
      practice to aid weight management.
AB  - BACKGROUND: The optimal role of general practice in population weight management
      remains unclear. The aim of this mixed-methods study was to test the feasibility
      of routinely weighing all adult patients attending their general practice as an
      intervention to aid weight management in clinical practice. METHODS: Consenting
      patients in six general practices were weighed at each presentation over a 12
      month period. Data were analysed using linear mixed growth models. Participants'
      interviews at the completion of the study were thematically analysed. RESULTS:
      The overall weight loss in patients who completed the study (n = 217) was 0.51 kg
      (P = 0.26; not significant); in patients who were obese (n = 106) there was a
      greater weight loss of 1.79 kg (P = 0.04). Patients were receptive to the
      intervention; however, there was disruption to clinical workflow. DISCUSSION:
      Routinely weighing adult patients in general practice is feasible, requires
      resources and may be associated with weight loss in patients who are obese.
      Further research is required to inform support for implementation within
      practices.

PMID- 29464232
TI  - Psychological distress and risky sexual behaviours among women aged 16-25 years
      in Victoria, Australia.
AB  - BACKGROUND: Identifying factors related to risky sexual behaviour may contribute
      to preventive and interventional approaches to reduce negative mental health
      outcomes among young women. The aim of this study was to investigate the
      association between psychological distress and risky sexual behaviours in females
      aged 16-25 years in Victoria, Australia. METHODS: Data were extracted from the
      Young Female Health Initiative (YFHI), a study in which participants were
      recruited via advertisements on Facebook. Logistic regression was used to assess
      associations between psychological distress, as measured by the Kessler 10 (K10)
      Psychological Distress Scale, and risky sexual behaviours. RESULTS: Data were
      available from 200 sexually active participants and 40 non-sexually active
      participants. We found that the K10 score was independently associated with sex
      while under the influence of alcohol or drugs (odds ratio: 1.7; 95% confidence
      intervals: 1.2, 2.7; P = 0.006). DISCUSSION: Although data were collected from a
      small sample of young women, we found that those with underlying psychological
      distress may adopt risky sexual behaviours, especially if concomitantly drinking
      alcohol or taking drugs.

PMID- 29464233
TI  - Understanding the decision to commence a dose administration aid.
AB  - BACKGROUND: The use of dose administration aids (DAAs), such as compartmentalised
      boxes (eg dosette) or medicine packs (eg Webster-pak), is common, particularly
      among patients with chronic disease. The aim of this study was to investigate
      factors influencing patients' decisions to commence using a DAA with a view to
      summarising implications for practice for general practitioners (GPs). METHODS:
      Semi-structured interviews were undertaken with participants living in a regional
      town in South Australia. Analysis of transcripts was facilitated using a
      qualitative analysis grid. RESULTS: Eight participants were interviewed. Four
      main themes included complexity of managing medications, DAAs as a cultural
      artefact, taking the lead in decision making, and weight of influence of health
      professionals. DISCUSSION: This study highlights the role of individual autonomy,
      close relatives and pharmacy staff in decisions to commence using a DAA. Tablets
      included in DAAs can take priority over inhaled and injected medications. GPs
      have an important role in ensuring that commencing a DAA helps empower patients
      to improve their healthcare management and does not inhibit communication between
      patient, doctor and pharmacist.

PMID- 29464234
TI  - You should get that mole checked out: Ethical and legal considerations of the
      unsolicited clinical opinion.
AB  - BACKGROUND: Legal and ethical obligations do not always align when doctors become
      aware of a clinical situation involving a person with whom they have no pre
      existing therapeutic relationship. Noting a potentially malignant skin lesion,
      such as a melanoma on a person outside the clinical setting, provides a pertinent
      example. OBJECTIVE: The aim of this article is to describe the legal, ethical and
      professional considerations surrounding proffering a dermatological opinion in
      the case of suspected melanoma outside the clinical setting. DISCUSSION: The
      application of professional and ethical standards may require the doctor to act
      in some way to alert the person of their findings in a context whereby there is
      no defined positive duty to do so in Australian law. The degree to which the
      doctor is ethically obligated to provide an unsolicited dermatological opinion is
      affected by numerous and, oftentimes, competing factors.

PMID- 29464236
TI  - AFP reviewers 2017.

PMID- 29464235
TI  - Occupational violence and staff safety in general practice.
AB  - BACKGROUND: The recent death of a Victorian surgeon who was assaulted by a member
      of the public when leaving work has re-highlighted the risk and potential cost of
      violence experienced by healthcare workers. OBJECTIVE: The aim of this article is
      to outline the risk of occupational violence experienced by doctors, and general
      practitioners in particular, and to discuss practical measures that can be taken
      to manage this risk. DISCUSSION: The majority of doctors have experienced
      aggression or violence in their workplaces in the past 12 months. Risks for
      violence include elements of workplace design, policy and procedures, and client
      factors. A series of practical tools designed to assist the assessment and
      management of risk of occupational violence are discussed.

PMID- 29464237
TI  - Magneto-structural correlations in oxalate-bridged Sr(ii)Cr(iii) coordination
      polymers: structure, magnetization, X-band, and high-field ESR studies.
AB  - The results of high-field electron spin resonance (HF-ESR) spectroscopy on the
      title 1D coordination polymers at frequencies up to 415 GHz, supported by X-ray
      diffraction, thermal, magnetic susceptibility, and X-band (10 GHz) ESR studies,
      are presented. The heterometallic compounds {SrCr2(phen)2(C2O4)4}.H2O (SrCrPhen)
      and {SrCr2(bpy)2(C2O4)4(H2O)}.5H2O (SrCrBpy) (phen = 1,10-phenanthroline, bpy =
      2,2'-bipyridine) were synthesized. Structural analysis revealed double oxalate
      bridged zigzag Sr-Cr chains while magnetic susceptibility studies showed
      paramagnetic behaviour of the complexes. HF-ESR spectroscopy data were analysed
      with a relevant spin-Hamiltonian, yielding the g, D and E parameters of the
      Cr(iii) ions. Both complexes showed small magnetic easy-axis type anisotropy with
      |D| ~ 1 K; SrCrBpy has uniaxial anisotropy while SrCrPhen has biaxial anisotropy.
      HF-ESR studies have enabled us to establish rational magneto-structural
      correlations and revealed significant differences between very similar crystal
      structures. Additionally, the ability of SrCrPhen and SrCrBpy to be single-source
      precursors for the formation of Sr-Cr oxides was investigated.

PMID- 29464238
TI  - A fluorescent microporous crystalline dendrimer discriminates vapour molecules.
AB  - A self-assembled crystalline microporous dendrimer framework (MDF) exhibits novel
      turn-on and ratiometric fluorescence upon exposure to solvent vapours. The donor
      acceptor character, combined with the large surface area (>650 m2 g-1), allows
      the MDF to discriminate vapours of volatile solvents with turn-on and colour
      change of photoluminescence.

PMID- 29464239
TI  - Effect of stacking order and in-plane strain on the electronic properties of
      bilayer GeSe.
AB  - Germanium selenide as a new layered material is promising for nanoelectronic
      applications due to its unique optoelectronic properties and tunable band gap. In
      this study, based on density functional theory, we systematically investigated
      the structure, stability, and electronic properties of bilayer germanium selenide
      with four different stacking orders (namely AA-, AB-, AC- and AD-stacking). The
      obtained results indicated that the band gap is dependent on the stacking order
      with an indirect band gap for AA- and AC-stacking and direct band gap for AB- and
      AD-stacking. In addition, we also found that the band gap of the GeSe bilayer
      with different stacking orders can be tuned by in-plane strain. The transition
      between the direct to indirect band gap or semiconductor to metal is tunable. In
      particular, the direct band gap of the AB-stacking germanium selenide bilayer can
      be tuned in a wide energy range under applied strain along the armchair
      direction.

PMID- 29464240
TI  - Gellan Gum-based luminal fillers for peripheral nerve regeneration: an in vivo
      study in the rat sciatic nerve repair model.
AB  - Peripheral nerve injuries (PNI) resulting in a gap to be bridged between the
      transected nerve ends are commonly reconstructed with autologous nerve tissue,
      but there is a need for valuable alternatives. This experimental work considers
      the innovative use of the biomaterial Gellan Gum (GG) as a luminal filler for
      nerve guidance channels made from chitosan with a 5% degree of acetylation. The
      engineered constructs should remodel the structural support given to regenerating
      axons by the so-called bands of Bungner. Four different GG formulations were
      produced by combining varying amounts of High-Acyl GG (HA-GG) and Methacrylated
      GG (MA-GG). The effective porosity of the freeze-dried networks was analysed by
      SEM and micro-CT 3D reconstructions, while the degradation and swelling abilities
      were characterized in vitro for up to 30 days. The metabolic activity and
      viability of immortalized Schwann cells seeded onto the freeze-dried networks
      were also evaluated. Finally, the developed hydrogel formulations were freeze
      dried within the chitosan nerve guides and implanted in a 10 mm rat sciatic nerve
      defect. Functional and histomorphological analyses after 3, 6, and 12 weeks in
      vivo revealed that although it did not result in improved nerve regeneration, the
      NGC25:75 formulations could provide a basis for further development of GG
      scaffolds as luminal fillers for hollow nerve guidance channels.

PMID- 29464241
TI  - Gas-stimuli-responsive molecularly imprinted polymer particles with switchable
      affinity for target protein.
AB  - Gas-responsive molecularly imprinted polymer (MIP) particles, which have
      nanocavities in their shell layer for protein recognition, were developed for the
      first time. The MIP particles showed higher affinity for the target protein
      inside a CO2-treated aqueous medium as compared to that under N2-treated
      conditions, while retaining selectivity to the target protein.

PMID- 29464242
TI  - Dynamical heterogeneities in ionic liquids as revealed from deuteron NMR.
AB  - The heterogeneity in dynamics has important consequences for understanding the
      viscosity, diffusion, ionic mobility, and the rates of chemical reactions in
      technology relevant systems such as polymers, metallic glasses, aqueous
      solutions, and inorganic materials. Herein, we study the spatial and dynamic
      heterogeneities in ionic liquids by means of solid state NMR spectroscopy. In the
      2H spectra of the protic ionic liquid [TEA][OTf] we observe anisotropic and
      isotropic signals at the same time. The spectra measured below the melting
      temperature at 306 K could be simulated by a superposition of the solid and
      liquid line shapes, which provided the transition enthalpies between the rigid
      and mobile fractions. Consequently, we measured the spin-lattice relaxation times
      T1 for the anisotropic and the isotropic signals for the temperature range
      between 203 and 436 K. Both dispersion curves could be fitted to models including
      rotational correlation times, activation barriers and rate constants. This
      approach allowed determining the rotational correlation times for the N-D
      molecular vector of the [TEA]+ cation in differently mobile environments. The
      mobility is only slightly different, as indicated by small differences in
      activation energies for these processes. The NMR correlation times for the highly
      mobile phase are linearly related to measured viscosities, which supports the
      applicability of the Stokes-Einstein-Debye relation.

PMID- 29464243
TI  - Sensitive detection of intracellular microRNA based on a flowerlike vector with
      catalytic hairpin assembly.
AB  - A flowerlike nanovector is developed for the fluorescence imaging and detection
      of miRNA in live cells with catalytic hairpin assembly. This horned vector
      provides a high loading efficiency of DNA amplifiers for multiple signal outputs
      and is applied to detect miRNA-21 in an average single HeLa cell, showing
      promising application in trace detection of intracellular biomolecules.

PMID- 29464244
TI  - Investigation of magneto-structural correlation based on a series of seven
      coordinated beta-diketone Dy(iii) single-ion magnets with C2v and C3v local
      symmetry.
AB  - A series of four beta-diketone mononuclear Dy(iii) complexes, namely
      Dy(Hthd)3(MeOH).2,5-Py (1), Dy(Hthd)3(Tppo) (2), Dy(Hthd)3(PyNO) (3), and
      Dy(Hthd)3(4-PyNO) (4) (Hthd = 2,2,6,6-tetramethyl-3,5-heptanedione, 2,5-Py = 2,5
      pyridine, Tppo = triphenylphosphine oxide, PyNO = pyridine N-oxide, 4-PyNO = 4
      methylpyridine N-oxide), have been isolated by reactions of Hthd, DyCl3.6H2O and
      an auxiliary ligand. X-ray crystallographic analysis revealed that complexes 1-4
      are all seven-coordinated mononuclear structures with C2v or C3v local symmetry.
      The magnetic measurements of complexes 1-4 revealed their field-induced single
      ion magnet (SIM) behavior, due to mixed low-lying states. The crystal field
      parameters and orientations of the magnetic easy axes were obtained from
      simulations of the DC magnetic data and an electrostatic model calculation. The
      magneto-structural correlation of seven-coordinated Dy(iii) SIMs with low
      symmetry coordination environments was further discussed.

PMID- 29464245
TI  - Friction and diffusion of a nano-colloidal disk in a two-dimensional solvent with
      a liquid-liquid transition.
AB  - We report on the friction and diffusion of a single mobile nano-colloidal disk,
      whose size and mass are one and two orders of magnitude, respectively, greater
      than the molecules of the host solvent; all particles are restricted to move in a
      two-dimensional space. Using molecular dynamics simulations, the variation of the
      transport coefficients as a function of the thermodynamic state of the supporting
      fluid, in particular, around those states in the neighbourhood of the liquid
      liquid phase coexistence, is investigated. The diffusion coefficient is
      determined through the fit of the mean-square displacement at long times and with
      the Green-Kubo relationship for the velocity autocorrelation function, whereas
      the friction coefficient is computed from the correlation of the fluctuating
      force. From the determination of the transport properties, the applicability of
      the Stokes-Einstein relation in two dimensions around the second critical point
      is discussed.

PMID- 29464246
TI  - Influence of Lewis acid strength on hydride transfer to unsaturated substrates.
AB  - Hydride transfer promoted by the coordination of a substrate molecule to a Lewis
      acid is a critical step in many catalytic transformations. This computational
      study investigates the nature of the interaction between a polar substrate
      molecule and a Lewis acid by examining the influence of Lewis acid strength on
      the ability to reduce (transfer a hydride to) the coordinated substrate molecule.
      To investigate this interaction, the coordination of 10 probe substrates to seven
      Lewis acids was analyzed. Coordination of the probe substrate molecules to a
      Lewis acid resulted in a more favorable reduction of the substrate molecule by 20
      70 kcal mol-1. Further examination of the coordination of the substrate molecules
      to Lewis acids of varying Lewis acid strengths resulted in a direct linear
      correlation between the ability of the Lewis acid-substrate adduct to accept a
      hydride and the Lewis acid strength. The linear correlations also revealed that
      between 44 and 70% of the Lewis acidity of the Lewis acids translated to the
      Lewis acid-substrate adducts. From the results obtained in this study, the
      minimum Lewis acid strength needed to activate the substrates for the reduction
      with [BH4]- and the implications of employing a Lewis acid to promote the
      reduction of an unsaturated polar substrate in catalytic reactions are also
      described.

PMID- 29464247
TI  - Role of the doping level in localized proton motions in acceptor-doped barium
      zirconate proton conductors.
AB  - Acceptor-doped barium zirconates are currently receiving considerable interest
      because of their high proton conductivity at intermediate temperatures, making
      them applicable as electrolytes in various electrochemical devices, but the
      mechanism of proton conduction is unclear. Here, we investigate the role of the
      acceptor-dopant level in the localized proton motions, i.e. proton transfers
      between oxygens and O-H reorientations, in hydrated samples of the proton
      conducting, acceptor-doped, perovskites BaZr1-xInxO3-x/2 with x = 0.10 and 0.20,
      using quasielastic neutron scattering (QENS). Analysis of the QENS spectra
      reveals that several proton transfer and O-H reorientational motions contribute
      to the QENS signal, as a consequence of the locally disordered nature of the
      structure due to the In doping of these materials, and establishes a generic and
      complex picture of localized proton dynamics in acceptor-doped barium zirconate
      based proton conductors. A comparison of the QENS results with vibrational
      spectroscopy data of the same materials, as reported in the literature, suggests
      a predominance of O-H reorientational motions in the observed dynamics. The
      highest doping level corresponds to a more distorted structure and faster
      dynamics, which thus indicates that some degree of structural disorder is
      favourable for high local proton mobility.

PMID- 29464248
TI  - Surface functional DNA density control by programmable molecular defects.
AB  - Programmable surface-patterned functional DNA density is achieved via
      manipulation of molecular-level defects through chemical lift-off lithography.
      Artificial SAM defects are well-tunable by a contact-induced reaction, enabling
      molecular environment guidance and DNA insertion to be spatially and
      quantitatively addressable. This straightforward molecular density control
      creates an advanced avenue toward fabricating multiplexed bioactive substrates.

PMID- 29464250
TI  - Ce-Doped bundled ultrafine diameter tungsten oxide nanowires with enhanced
      electrochromic performance.
AB  - Cerium (Ce)-doped tungsten oxide nanostructures were synthesised using a simple
      solvothermal method from cerium chloride salt (CeCl3.7H2O) and tungsten
      hexachloride (WCl6) precursors. The as-prepared samples were thoroughly
      characterised using electron microscopies, X-ray diffraction (XRD), X-ray
      photoelectron spectroscopy (XPS) and Raman spectroscopy. The electrochromic
      performance of different samples was evaluated using a custom-built UV-VIS
      spectrometer and an electrochemistry technique. The results showed that the as
      prepared samples underwent morphological evolution with the increase in the Ce/W
      molar ratio, from long, thin and bundled nanowires, through shorter and thicker
      nanowires to mixed nanowire bundles and nanoparticle agglomerates. From
      electrochemical testing, we found that the Ce-doped tungsten oxides exhibited
      higher optical contrasts of 44.3%, 49.7% and 39.4% for the 1 : 15, 1 : 10 and 1 :
      5 Ce/W ratios respectively, compared with 37.4% for the pure W18O49 nanowires.
      The Ce/W = 1 : 15 samples presented an improved colouration efficiency of 67.3
      cm2 C-1 against 62 cm2 C-1 for pure W18O49. This work demonstrated that the Ce
      doped W18O49 nanowires are very promising candidate materials for the design and
      construction of electrochemical chromic devices with largely improved efficiency,
      contrast and stability. The results from this work suggested that smart
      electrochromic devices based on current Ce-doped WOx nanomaterials could be
      further developed for future energy-related applications.

PMID- 29464252
TI  - A luminescent supramolecular Cu2I2(NH3)2-sandwiched Cu3(pyrazolate)3 adduct as a
      temperature sensor.
AB  - A highly luminescent supramolecular Cu2I2(NH3)2-sandwiched Cu3(pyrazolate)3
      adduct was reported as a temperature sensor. The adduct is stabilized by the
      synergy of intermolecular Cu3I (pi acidbase), CuCu and NH interactions, to form a
      Cu8I2 cluster. The emission intensity exhibits a temperature-dependent effect in
      the solid state with a sensitivity of -0.685% K-1. DFT and TDDFT calculations
      revealed that the luminescence originates from the triplet state of Cu8I2 cluster
      centered charge transfer (3CC).

PMID- 29464253
TI  - Planar chiral [2.2]paracyclophane-based phosphine-phenols: use in
      enantioselective [3 + 2] annulations of allenoates and N-tosylimines.
AB  - Planar chiral [2.2]paracyclophane-based phosphine-phenol catalysts, which have a
      benzene ring spacer inserted between the pseudo-ortho-substituted
      [2.2]paracyclophanol skeleton and the diarylphosphino group, are highly suitable
      for enantioselective [3 + 2] annulations of allenoates and N-tosylimines. These
      catalysts can be tuned by changing the substituent on the benzene rings of the
      diarylphosphino group. The observed enantioselectivity of 92% is the highest
      reported to date for phosphine-catalyzed annulations of unsubstituted allenic
      esters and N-tosylaldimines.

PMID- 29464255
TI  - Plasmonic nose: integrating the MOF-enabled molecular preconcentration effect
      with a plasmonic array for recognition of molecular-level volatile organic
      compounds.
AB  - Timely detection of toxic vapor is vital for safeguarding people's lives. Herein,
      we design a plasmonic nose based on a zeolitic imidazolate framework (ZIF)
      encapsulated Ag nanocube array for ultratrace recognition of VOC vapor. The
      plasmonic nose enables in situ adsorption kinetics and recognition of various
      VOCs at ppm levels, eliminating false positives. Our approach provides a paradigm
      shift to next-generation, effective and specific gas sensors.

PMID- 29464254
TI  - Buchwald-Hartwig amination using Pd(i) dimer precatalysts supported by biaryl
      phosphine ligands.
AB  - We report the synthesis of air-stable Pd(i) dimer complexes featuring biaryl
      phosphine ligands. Catalytic experiments suggest that these complexes are
      competent precatalysts that can mediate cross-coupling amination reactions
      between aryl halides with both aliphatic and aromatic amine nucleophiles. This
      work represents an expansion of the air-stable precatalyst toolbox for Pd
      catalyzed cross-coupling transformations.

PMID- 29464256
TI  - Quantitative analysis of UV photolesions suggests that cyclobutane pyrimidine
      dimers produced in mouse skin by UVB are more mutagenic than those produced by
      UVC.
AB  - The amount of photolesions produced in DNA after exposure to physiological doses
      of ultraviolet radiation (UVR) can be estimated with high sensitivity and at low
      cost through an immunological assay, ELISA, which, however, provides only a
      relative estimate that cannot be used for comparisons between different
      photolesions such as cyclobutane pyrimidine dimer (CPD) and pyrimidine(6
      4)pyrimidone photoproduct (64PP) or for analysis of the genotoxicity of
      photolesions on a molecular basis. To solve this drawback of ELISA, we introduced
      a set of UVR-exposed, calibration DNA whose photolesion amounts were
      predetermined and estimated the absolute molecular amounts of CPDs and 64PPs
      produced in mouse skin exposed to UVC and UVB. We confirmed previously reported
      observations that UVC induced more photolesions in the skin than UVB at the same
      dose, and that both types of UVR produced more CPDs than 64PPs. The UVR
      protection abilities of the cornified and epidermal layers for the lower tissues
      were also evaluated quantitatively. We noticed that the values of absorbance
      obtained in ELISA were not always proportional to the molecular amounts of the
      lesion, especially for CPD, cautioning against the direct use of ELISA absorbance
      data for estimation of the photolesion amounts. We further estimated the
      mutagenicity of a CPD produced by UVC and UVB in the epidermis and dermis using
      the mutation data from our previous studies with mouse skin and found that CPDs
      produced in the epidermis by UVB were more than two-fold mutagenic than those by
      UVC, which suggests that the properties of CPDs produced by UVC and UVB might be
      different. The difference may originate from the wavelength-dependent methyl CpG
      preference of CPD formation. In addition, the mutagenicity of CPDs in the dermis
      was lower than that in the epidermis irrespective of the UVR source, suggesting a
      higher efficiency in the dermis to reduce the genotoxicity of CPDs produced
      within it. We also estimated the minimum amount of photolesions required to
      induce the mutation induction suppression (MIS) response in the epidermis to be
      around 15 64PPs or 100 CPDs per million bases in DNA as the mean estimate from
      UVC and UVB-induced MIS.

PMID- 29464257
TI  - A fabrication method of gold coated colloidosomes and their application as
      targeted drug carriers.
AB  - Colloidosomes have attracted considerable attention in recent years because of
      their potential applications in a range of industries, such as food, bioreactors
      and medicine. However, traditional polymer shell colloidosomes leak low molecular
      weight encapsulated materials due to their intrinsic shell permeability. Here, we
      report aqueous core colloidosomes coated with a gold shell, which make the
      capsules impermeable. The shells can be ruptured using ultrasound. The gold
      coated colloidosomes are prepared by making an aqueous core capsule with a
      polymer shell and then adding HAuCl4, surfactant and l-ascorbic acid to form a
      second shell. We propose to use the capsules as drug carriers. The gold coated
      colloidosomes demonstrate a low cytotoxicity and after triggering, both
      encapsulated doxorubicin and broken gold fragments kill cancer cells. In
      addition, we set up a targeting model by modifying the gold shell colloidosomes
      using 4,4'-dithiodibutyric acid and crosslinking them with proteins-rabbit
      immunoglobulin G (IgG). Label-free surface plasmon resonance was used to test the
      specific targeting of the functional gold shells with rabbit antigen. The results
      demonstrate that a new type of functional gold coated colloidosome with non
      permeability, ultrasound sensitivity and immunoassay targeting could be applied
      to many medical applications.

PMID- 29464258
TI  - Reconstitution of composite actin and keratin networks in vesicles.
AB  - Although cytoskeletal networks are interpenetrating and interacting in living
      cells, very little is understood as to the effect their interaction has on their
      properties. Here, as a step towards elucidating the synergistic cellular role of
      these structural proteins, we investigate isolated keratin and actin composites
      and show how the in vitro network formation of keratin influences the properties
      of actin networks and vice versa. By encapsulating purified composite networks
      into vesicles and separating the time scales of network formation we are able to
      demonstrate that the actin network stabilizes keratin networks by providing an
      elastic resistance to their collapse in vitro.

PMID- 29464260
TI  - Dual signal amplification strategy for high-sensitivity detection of copper
      species in bio-samples with a tunable dynamic range.
AB  - A facile and sensitive method with a tunable dynamic range has been proposed for
      the detection of Cu2+ based on the self-cleavage of Cu2+-specific DNAzyme and the
      Cu2+-based inhibition of HRP activity, and this method was applied to evaluate
      the copper species in healthy people and WD patients.

PMID- 29464261
TI  - An organocatalyzed Stetter reaction as a bio-inspired tool for the synthesis of
      nucleic acid-based bioconjugates.
AB  - An N-Heterocyclic Carbene (NHC) catalyzed biomimetic Stetter reaction was applied
      for the first time as a bioconjugation reaction to sensitive nucleoside-type
      biomolecules to provide original pyrrole linked nucleolipids. A versatile
      approach allowed the functionalization of thymidine at the three reactive
      positions (O-5', O-3' and N-3) providing a structural diversity oriented
      synthesis. This strategy was applied to the synthesis of an original
      glyconucleolipid amphiphile in the hope that the pyrrole aromatic moiety would
      induce additional self-assembling properties.

PMID- 29464262
TI  - Lysine-based amino-functionalized lipids for gene transfection: the influence of
      the chain composition on 2D properties.
AB  - The influence of the chain composition on the physical-chemical properties will
      be discussed for five transfection lipids containing the same lysine-based head
      group. For this purpose, the chain composition will be gradually varied from
      saturated tetradecyl (C14:0) and hexadecyl (C16:0) chains to longer but
      unsaturated oleyl (C18:1) chains with double bonds in the cis configuration. In
      this work, we investigated the lipids as Langmuir monolayers at the air-water
      interface in the absence and presence of calf thymus DNA applying different
      techniques such as infrared reflection absorption spectroscopy (IRRAS) and
      grazing incidence X-ray diffraction (GIXD). The replacement of saturated
      tetradecyl (C14:0) and hexadecyl (C16:0) chains by unsaturated oleyl (C18:1)
      chains increases the fluidity of the lipid monolayer: TH10 < TT10 < OH10 < OT10 <
      OO10 resulting in a smaller packing density. TH10 forms the stiffest and OO10 the
      most fluid monolayer in this structure-property study. OO10 has a higher
      protonation degree compared to the saturated lipids TT10 and TH10 as well as to
      the hybrids OT10 and OH10 because of a better accessibility of the amine groups.
      Depending on the bulk pH, different scenarios of DNA coupling to the lipid
      monolayers have been proposed.

PMID- 29464263
TI  - Homogeneous melting near the superheat limit of hard-sphere crystals.
AB  - A defect-free crystal can be superheated into a metastable state above its
      melting point and eventually melts via homogeneous nucleation. Further increasing
      the temperature leads to the metastable crystal becoming unstable and melting
      catastrophically once beyond its superheat limit. The homogeneous melting is not
      well studied near the superheat limit and this limit is difficult to measure
      accurately, even for the simplest model of hard-sphere crystals. Here our
      molecular-dynamics simulations identify its superheat limit at volume fraction
      philimit = 0.494 +/- 0.003, which is higher than the previous theoretical
      estimations. We found that the hard-sphere crystal at the superheat limit does
      not satisfy Born's melting criterion, but has a vanishing bulk modulus, i.e. a
      spinodal instability, which preempts other thermodynamic or mechanical
      instabilities. At the strong superheating regime, the nucleation deviates from
      the assumptions in the classical nucleation theory. In contrast to
      crystallization which often develops nuclei with various intermediate structures,
      the melting of face-centered cubic (fcc) hard-sphere crystal does not produce
      intermediate structures such as body-centered cubic (bcc) crystallites although
      bcc is more stable than fcc at the strong superheating regime. Moreover, we found
      that the time evolutions of the order parameters and the pressure all exhibit a
      compressed exponential function, in contrast to the stretched exponential
      relaxation of supercooled liquids. The compressed exponential functions have the
      same exponent, which poses a new challenge to theory.

PMID- 29464264
TI  - Push-pull D-pi-Ru-pi-A chromophores: synthesis and electrochemical, photophysical
      and second-order nonlinear optical properties.
AB  - The present work describes the one-pot synthesis and electrochemical,
      photophysical and second-order nonlinear optical (NLO) properties of a series of
      dipolar pi-delocalized Ru(ii) dialkynyl complexes. The eight new asymmetrical D
      pi-Ru-pi-A push-pull chromophores incorporate pyranylidene ligands as pro
      aromatic donor groups (D) and formaldehyde, indane-1,3-dione, pyrimidine or
      pyrimidinium as electron-attracting groups (A) separated by ruthenium bis
      acetylide fragments and pi-conjugated linkers. The second-order nonlinear optical
      (NLO) properties of all eight complexes were determined by the Electric-Field
      Induced Second Harmonic generation (EFISH) technique (operating at 1907 nm), and
      were compared to those of their purely organic analogs. All investigated
      compounds (organic and organometallic) exhibited positive MUbeta values, which
      dramatically increased for the complexes due to the presence of ruthenium in the
      pi-conjugated core. The second-order NLO response could also be easily modulated
      by changing the nature of alkynyl substituents. The most promising ruthenium
      complexes 7 and 8 of the series with the pyrimidinium fragment displayed MUbeta
      values of 14 000 * 10-48 esu. The effect of structural modifications on the redox
      and spectroscopic properties of the complexes was also studied. The
      intramolecular charge transfer (ICT) occurring through the ruthenium center of
      the push-pull sigma-dialkynyl complexes was investigated by combining
      experimental and theoretical data.

PMID- 29464265
TI  - Recent progress of C-glycosylation methods in the total synthesis of natural
      products and pharmaceuticals.
AB  - Chemical C-glycosylation has been well developed to improve stereoselectivity in
      recent years. Due to its high efficiency to build C-glycosides or O-cyclic
      compounds, C-glycosylation has found widespread use in the synthesis of
      biologically active molecules. This review highlights the C-glycosylation methods
      that have been practised in the total synthesis of natural products and
      pharmaceuticals in the past decade.

PMID- 29464266
TI  - [Painful recurrent leg ulcers].

PMID- 29464267
TI  - Syria: public health disasters in the era of no world order.

PMID- 29464268
TI  - Reversible Dilation of Cerebral Macrovascular Changes in MELAS Episodes.
AB  - PURPOSE: To investigate the cerebral macrovascular changes as well as the
      relationship of large vessels and cerebral blood flow (CBF) in mitochondrial
      encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) using
      magnetic resonance angiography (MRA) and arterial spin labeling (ASL) perfusion
      MR imaging (MRI). METHODS: A total of 20 patients diagnosed with MELAS (12 males,
      8 females; mean age, 23.3 years) underwent conventional MRI, time-of-flight (TOF)
      MRA and three dimensional ASL. Follow-up scans were performed in 10 patients. The
      changes of cerebral arteries and branches on MRA images from both acute and
      recovery patients were independently evaluated by two radiologists. Lesion
      distribution and CBF were observed on the integrated maps of MRA and ASL.
      RESULTS: In 14 patients with clinical onsets, increased CBF was observed in all
      stroke-like lesions. Dilations of a single artery (four middle cerebral arteries,
      two posterior cerebral arteries) were found in six patients. Dilations of
      multiple arteries (two anterior cerebral arteries, seven middle cerebral
      arteries, six posterior cerebral arteries) were found in seven patients. Normal
      angiography was shown in one acute patient. Cortical terminal branches feeding
      the lesion areas were more obviously dilated than the main trunks. The dilated
      vessels returned to normal on follow-up scans concurrently with decreased CBF in
      nine patients who were resuscitated from episode attacks. Vasodilation was even
      seen in one preclinical patient who suffered a recurrent episode 50 days later.
      CONCLUSION: Reversible dilation of cerebral macrovascular changes could be a new
      feature of MELAS and a presumed reason for fluctuant CBF. It would shed new light
      on the mitochondrial angiopathy.

PMID- 29464269
TI  - Glioma grading by dynamic susceptibility contrast perfusion and 11C-methionine
      positron emission tomography using different regions of interest.
AB  - PURPOSE: The use of dynamic susceptibility contrast (DSC) perfusion and 11C
      methionine positron emission tomography (MET-PET) for glioma grading is currently
      not standardized. The purpose of this study was to identify regions of interest
      (ROIs) that enable the best performance and clinical applicability in both
      methods, as well as to evaluate the complementarity of DSC perfusion and MET-PET
      in spatial hotspot definition. METHODS: In 41 patient PET/MRI datasets, different
      ROIs were drawn: in T2-hyperintense tumour, in T2-hyperintense tumour and
      adjacent oedema and in tumour areas with contrast enhancement, altered perfusion
      or pathological radiotracer uptake. The performance of DSC perfusion and MET-PET
      using the different ROIs to distinguish high- and low-grade gliomas was assessed.
      The spatial overlap of hotspots identified by DSC perfusion and MET-PET was
      assessed visually. RESULTS: ROIs in T2 fluid attenuated inversion recovery
      (FLAIR) sequence-hyperintense tumour revealed the most significant differences
      between high- and low-grade gliomas and reached the highest diagnostic
      performance in both DSC perfusion (p = 0.046; area under the curve = 0.74) and
      MET-PET (p = 0.007; area under the curve = 0.80). The combination of methods
      yielded an area under the curve of 0.80. Hotspots were completely overlapped in
      one half of the patients, partially overlapped in one third of the patients and
      present in only one method in approximately 20% of the patients. CONCLUSIONS: For
      multi-parametric examinations with DSC perfusion and MET-PET, we recommend an ROI
      definition based on T2-hyperintense tumour. DSC perfusion and MET-PET contain
      complementary information concerning the spatial hotspot definition.

PMID- 29464271
TI  - [Noise-induced neurodegeneration in the central auditory pathway : An overview of
      experimental studies in a mouse model].
AB  - BACKGROUND: A noise trauma induces central nervous system pathologies, which
      generate deficits in hearing and perception of sound. OBJECTIVE: Are degenerative
      mechanisms in the central auditory system a direct impact of overstimulation or
      an effect of acoustic deprivation? MATERIALS AND METHODS: Detection of cell death
      in a mouse model of noise-induced hearing loss at different times after single or
      repeated noise exposure. RESULTS: A single noise exposure (3 h, 115 dB SPL, 5-20
      kHz) induces acute (<=1 day) and long-term (observation period 14 days)
      degeneration, particularly in subcortical structures. Repeated noise trauma is
      followed by pathologies in the auditory thalamus and cortex. CONCLUSION: Noise
      has a direct impact on basal structures of the central auditory system; a
      protection of cortical areas is possibly due to inhibitory neuronal projections.
      Degenerative mechanisms in higher structures of the pre-damaged system point to
      an increased impairment of complex processing of acoustic information.

PMID- 29464270
TI  - Diabetes modifies the role of prostanoids and potassium channels which regulate
      the hypereactivity of the rabbit renal artery to BNP.
AB  - Diabetic nephropathy is associated with increased risk of cardiovascular disease.
      B-type natriuretic peptide (BNP) plays an important role in cardiovascular
      pathophysiology and therapeutics. The aim of the present study was to investigate
      the influence of experimental diabetes on the mechanisms that regulate the
      relaxant response of the rabbit renal artery to BNP. Arterial relaxations to BNP
      were enhanced in diabetic rabbits. Indomethacin enhanced BNP-induced relaxation
      in control rabbits but showed no effect in diabetic rabbits. BNP-induced release
      of thromboxane A2 or prostacyclin was not different in both groups of animals.
      Iberiotoxin had no effect on relaxations to BNP in both groups of animals.
      Charybdotoxin displaced to the right the concentration-response curve to BNP in
      both group of animals, and inhibited BNP-induced relaxation only in diabetic
      rabbits. Glibenclamide did not modify the BNP-induced relaxations in control
      rabbits, but inhibited it in diabetic rabbits. These results suggest that
      diabetes induces hypereactivity of the rabbit renal artery to BNP by mechanisms
      that at least include (1) a reduced vasoconstrictor influence of arachidonic acid
      metabolites via cyclooxygenase 2, which is not related with changes in
      thromboxane A2 and prostacyclin release from the arterial wall and (2) a
      selectively increased modulatory activity of KATP and endothelial IKCa channels.

PMID- 29464272
TI  - Quantification of organic solvents in aquatic toys and swimming learning devices
      and evaluation of their influence on the smell properties of the corresponding
      products.
AB  - Based on the observation that the characteristic odour of inflatable aquatic toys
      for children is predominantly caused by residues of hazardous organic solvents,
      the concentrations of cyclohexanone, isophorone and phenol were determined in a
      selection of 20 products obtained from online suppliers located in Germany.
      Analytes were extracted with dichloromethane after the addition of non-labelled
      internal standards, and the volatile fraction was isolated using solvent-assisted
      flavour evaporation (SAFE). Extracts were then concentrated by Vigreux
      distillation and analysed by means of gas chromatography with mass spectrometric
      detection (GC-MS). Furthermore, each sample was evaluated regarding its specific
      olfactory properties by an expert sensory panel. While some samples did not
      contain significant amounts of solvents, cyclohexanone concentrations above the
      lower limit of quantification (LLOQ) were determined in nine samples with six
      samples containing high concentrations ranging from about 1 to 7 g/kg
      cyclohexanone. Isophorone concentrations above the LLOQ were observed in eight
      samples. Thereby, six products contained between 0.3 and 1.6 g/kg isophorone and
      the remaining two samples contained even about 5 g/kg isophorone, each. Likewise,
      phenol concentrations exceeded the LLOQ in 14 cases, with four samples containing
      elevated amounts ranging from about 140 to 280 mg/kg phenol.

PMID- 29464273
TI  - [Perianal inflammatory diseases : Classification and imaging].
AB  - During the past 30 years, classifications and scoring systems have been developed
      in order to evaluate and objectify the degree and activity of anorectal fistulas.
      Only a few of these disease-specific instruments have been adopted into daily
      clinical routine. Generally, clinicians tend to use global medical judgement
      rather than numeric activity indices, which often seem complex and time
      consuming. Activity scores in Crohn disease, however, appeared to be very useful
      in clinical trials regarding evaluation of therapy response. Thus, activity
      indices must be simple and reproducible. The years 1976 and 1995, in which the
      Parks Classification and Perianal Disease Activity Index (PDAI) were established,
      can be considered milestone years for classifying patients with anorectal
      fistulizing disease. These instruments should be recognized at present as the
      gold standard for evaluating the complexity as well as the severity of anorectal
      fistulas and perianal Crohn disease.

PMID- 29464274
TI  - Percutaneous microwave ablation for local control of metastatic renal cell
      carcinoma.
AB  - PURPOSE: The purpose of the article is to evaluate the safety and oncologic
      efficacy of microwave ablation for metastatic renal cell carcinoma (mRCC).
      MATERIALS AND METHODS: From September 2011 to December 2016, 33 mRCC were ablated
      in 18 patients using percutaneous microwave ablation. Sites of mRCC include
      retroperitoneum (n = 12), contralateral kidney (n = 6), liver (n = 6), lung (n =
      5), adrenal gland (n = 5). Technical success, local, and distant tumor
      progression, and complications were assessed at immediate and follow-up imaging.
      The Kaplan-Meier method was used for survival analysis. RESULTS: Technical
      success was achieved for 33/33 (100%) mRCC tumors. Ablation provided durable
      local control for 28/30 (93%) mRCC tumors in 17 patients at a median duration of
      clinical and imaging follow-up of 1.6 years (IQR 0.7-3.6) and 0.8 years (IQR 0.5
      2.7), respectively. In-hospital and perioperative mortality was 0%. There were 5
      (15%) procedure-related complications including one high-grade event (Clavien
      Dindo III). Four patients have died from mRCC at a median of 1.3 years (range 0.7
      5.1) following ablation. Estimated OS (95% CI number still at risk) at 1, 2, and
      5 years were 86% (53-96%, 11), 75% (39-92%, 8), and 75% (39-92%, 3),
      respectively. CONCLUSIONS: Microwave ablation of oligometastatic renal cell
      carcinoma is safe and provides durable local control in appropriately selected
      patients.

PMID- 29464275
TI  - Fat halo sign.

PMID- 29464276
TI  - After the fall: improving osteoporosis treatment following hip fracture.
AB  - : Osteoporotic hip fractures can be life changing and can increase mortality.
      Treatment of osteoporosis following hip fracture is often delayed. We began
      offering osteoporosis medication during hospitalization for hip fracture,
      dramatically increasing the number of patients meeting standard of care.
      INTRODUCTION: Osteoporotic hip fracture is a debilitating condition with major
      morbidity and mortality implications. Osteoporosis medication given within 90
      days of hip fracture improves mortality and reduces risk of future fractures. The
      aim of this project was to improve rates of timely osteoporosis treatment
      following fragility hip fracture. METHODS: This was a two-step intervention
      utilizing the Plan-Do-Study-Act cycle, beginning with resident-focused education
      in cycle 1. In cycle 2, we offered osteoporosis medication to inpatients for hip
      fracture with help from a new electronic order set. RESULTS: Prior to this
      intervention, 32% of patients received osteoporosis medication within 90 days of
      fragility hip fracture; this improved to 81% after intervention. CONCLUSIONS:
      Resident education and an electronic order set dramatically improved the
      percentage of patients meeting standard of care with osteoporosis pharmacotherapy
      following fragility fracture.

PMID- 29464277
TI  - Health-related quality of life during the first year after a hip fracture:
      results of the Mexican arm of the International Cost and Utility Related to
      Osteoporotic Fractures Study (MexICUROS).
AB  - : We investigated changes in health-related quality of life (HRQoL) due to hip
      fracture in Mexican adults aged >= 50 years during the first year post-fracture.
      Mean accumulated loss was 0.27 quality-adjusted life years (QALYs). HRQoL before
      fracture was the main contributor to explain the loss of QALYs. INTRODUCTION: We
      aimed to estimate the health-related quality of life (HRQoL) loss over 1 year in
      patients sustaining a hip fracture in Mexico. METHODS: Individuals aged >= 50
      years old with diagnosis of a low-energy-induced hip fracture enrolled in the
      International Costs and Utilities Related to Osteoporotic Fractures Study
      (ICUROS) composed the study population. After a recall of their own pre-fracture
      status, HRQoL was prospectively collected in three phases over 12 months of
      follow-up using EQ-5D-3L. The UK preference weight set was applied to calculate
      the utility values. The accumulated quality-adjusted life years (QALYs) loss in
      the first year post-fracture was estimated using the trapezoid method.
      Multivariate regression analysis allowed identifying determinants of QALYs loss.
      RESULTS: One hundred ninety-three patients (mean +/- SD age 77.2 +/- 9.9 years;
      80% women; 15.5% with prior fracture in the last 5 years; 78% in low-income
      category) were evaluated. Mean (95% CI) utility value before fracture was 0.64
      (0.59-0.68). It dropped to 0.01 (0.01-0.02) immediately after fracture and then
      improved to 0.46 (0.42-0.51) and 0.60 (0.55-0.64) at 4 and 12 months post
      fracture, respectively. Disregarding fracture-related mortality, accumulated
      QALYs loss over the first year was 0.27 (0.24-0.30) QALYs. Mobility, self-care,
      and usual activities were the most affected domains throughout the whole year.
      HRQoL before fracture was the main contributor to explain the loss of QALYs.
      CONCLUSIONS: Hip fractures reduce dramatically the HRQoL, with the loss sustained
      at least over the first year post-fracture in Mexico. The utility values derived
      from this study can be used in future economic evaluations.

PMID- 29464278
TI  - Biochemical Responses in Freshwater Fish Exposed to Insecticide Propoxur.
AB  - Although designed to control pests selectively, there is some evidence that
      environmental contamination by pesticides increases risks for humans and
      wildlife. In the present study, we evaluated biomarkers of oxidative stress in
      Astyanax jacuhiensis exposed to (5, 15 and 30 ug L-1) of carbamate Propoxur (PPX)
      for 96 h. Glutathione S-transferase (GST) in liver and gills showed reduced
      activity in all PPX concentrations tested. Acetylcholinesterase (AChE) activities
      reduced in brain and muscle at concentrations 15 and 30 ug L-1 of PPX. Lipid
      peroxidation (LPO) and hydrogen peroxide (HP) had no significant differences. In
      the brain, protein carbonyl (PC) increased in all groups treated with PPX.
      Although PPX is a selective pesticide, it causes oxidative damage and enzyme
      alteration in fish. This study pointed out some biomarkers that could be used to
      assess effects of environmentally relevant concentrations of pesticides, and
      infer about studies using fish as bioindicator.

PMID- 29464279
TI  - Biodegradability of Chlorophenols in Surface Waters from the Urban Area of Buenos
      Aires.
AB  - Biodegradability of 2-Chlorophenol (2-CP), 3-Chlorophenol (3-CP), 4-Chlorophenol
      (4-CP), 2,4-Dichlorophenol (2,4-DCP) and 2,4,6 Trichlorophenol (2,4,6-TCP) has
      been tested in surface waters in the urban area of Buenos Aires. Samples were
      taken from the La Plata River and from the Reconquista and Matanza-Riachuelo
      basins, with a total amount of 18 sampling points. Water quality was established
      measuring chemical oxygen demand (COD), biochemical oxygen demand (BOD5), and
      both Escherichia coli and Enterococcus counts. Biodegradability was carried out
      by a respirometric method, using a concentration of 20 mg L-1 of chlorophenol,
      and the surface water as inoculum. Chlorophenols concentration in the same water
      samples were simultaneously measured by a solid phase microextraction (SPME)
      procedure followed by gas chromatography-mass spectrometry (GC-MS). 2,4-DCP was
      the most degradable compound followed by 2,4,6-TCP, 4-CP, 3-CP and 2-CP.
      Biodegradability showed no correlation with compound concentration. At most
      sampling points the concentration was below the detection limit for all
      congeners. Biodegradability does not correlate even with COD, BOD5, or fecal
      contamination. Biodegradability assays highlighted information about bacterial
      exposure to contaminants that parameters routinely used for watercourse
      characterization do not reveal. For this reason, they might be a helpful tool to
      complete the characterization of a site.

PMID- 29464280
TI  - [Internal emergency cases at the interface of outpatient and inpatient - part 2].

PMID- 29464281
TI  - Varying susceptibility of clinical and environmental Scedosporium isolates to
      chemical oxidative stress in conidial germination.
AB  - Scedosporium species are opportunistic pathogens causing a great variety of
      infections in both immunocompetent and immunocompromised individuals. The
      Scedosporium genus ranks the second among the filamentous fungi colonizing the
      airways of patients with cystic fibrosis (CF), after Aspergillus fumigatus, and
      most species are capable to chronically colonize the respiratory tract of these
      patients. Nevertheless, few data are available regarding evasion of the inhaled
      conidia to the host immune response. Upon microbial infection, macrophages and
      neutrophils release reactive oxygen species (ROS). To colonize the respiratory
      tract, the conidia need to germinate despite the oxidative stress generated by
      phagocytic cells. Germination of spores from different clinical or environmental
      isolates of the major Scedosporium species was investigated in oxidative stress
      conditions. All tested species showed susceptibility to oxidative stress.
      However, when comparing clinical and environmental isolates, differences in
      germination capabilities under oxidative stress conditions were seen between
      species as well as within each species. Among environmental isolates,
      Scedosporium aurantiacum isolates were the most resistant to oxidative stress
      whereas Scedosporium dehoogii were the most susceptible. Overall, the differences
      observed between Scedosporium species in the capacity to germinate under
      oxidative stress conditions could explain their varying prevalence and
      pathogenicity.

PMID- 29464283
TI  - [Osteoarthritis of the shoulder: pathogenesis, diagnostics and conservative
      treatment options].
AB  - PATHOGENESIS: Osteoarthritis of the shoulder is characterized by a progressive
      degenerative process, which is based on chronic inflammation with intra-articular
      release of different cytokines and proteolytic enzymes. The main predisposing
      factors are a history of trauma or surgery, as well as chronic overuse or
      instability of the glenohumeral joint. Affected patients especially suffer from
      impaired joint function and pain, which are often associated with cognitive and
      psychosocial restrictions. DIAGNOSTICS: Possible co-pathologies have to be
      evaluated carefully both clinically and radiologically as they must be taken into
      account in the therapeutic procedure. If arthroplasty of the shoulder is planned,
      a pre-operative CT scan is mandatory in order to evaluate the bone stock of the
      glenoid, which has a decisive influence on the choice of implant. TREATMENT:
      Conservative treatment options are oral pain medication, physical therapy, and
      intra-articular injections, whereby, in comparison to corticosteroids, hyaluronic
      acid seems to be advantageous especially with respect to the duration of a
      positive clinical effect.

PMID- 29464284
TI  - Degradation of the mitochondrial complex I assembly factor TMEM126B under chronic
      hypoxia.
AB  - Cell stress such as hypoxia elicits adaptive responses, also on the level of
      mitochondria, and in part is mediated by the hypoxia-inducible factor (HIF)
      1alpha. Adaptation of mitochondria towards acute hypoxic conditions is reasonably
      well understood, while regulatory mechanisms, especially of respiratory chain
      assembly factors, under chronic hypoxia remains elusive. One of these assembly
      factors is transmembrane protein 126B (TMEM126B). This protein is part of the
      mitochondrial complex I assembly machinery. We identified changes in complex I
      abundance under chronic hypoxia, in association with impaired substrate-specific
      mitochondrial respiration. Complexome profiling of isolated mitochondria of the
      human leukemia monocytic cell line THP-1 revealed HIF-1alpha-dependent deficits
      in complex I assembly and mitochondrial complex I assembly complex (MCIA)
      abundance. Of all mitochondrial MCIA members, we proved a selective HIF-1
      dependent decrease of TMEM126B under chronic hypoxia. Mechanistically, HIF-1alpha
      induces the E3-ubiquitin ligase F-box/WD repeat-containing protein 1A (beta
      TrCP1), which in turn facilitates the proteolytic degradation of TMEM126B.
      Attenuating a functional complex I assembly appears critical for cellular
      adaptation towards chronic hypoxia and is linked to destruction of the
      mitochondrial assembly factor TMEM126B.

PMID- 29464286
TI  - Dentoalveolar characteristics in children with juvenile idiopathic arthritis.
AB  - PURPOSE: Juvenile idiopathic arthritis (JIA) is an autoimmune disease with
      multiple potential causal factors. In case of temporomandibular joint (TMJ)
      affection, the inflammatory reaction can result in restricted mandibular growth
      with implied skeletal and facial deformities. Aim of the present study was to
      examine dentoalveolar and occlusion characteristics in children with JIA.
      PATIENTS AND METHODS: The sample consisted of 66 children (27 boys, 39 girls)
      with JIA. Thirty-three of them showed unilateral or bilateral condylar
      destruction, while the other half did not manifest any TMJ involvement.
      Corresponding dental casts of these patients were evaluated and Angle
      classification, overjet, overbite, crossbite, crowding, and ectopic teeth were
      registered. All dental casts were subsequently scanned and digitized to analyze
      26 additional variables. Subgroups according to sex and condylar affection were
      formed. Statistical analysis was performed using Fisher's least significant
      difference (LSD) post hoc test of analysis of variance (ANOVA). RESULTS: The
      prevalence of Class II, division 1 malocclusion in this JIA sample was high
      (28.8%). Compared to girls, boys had significantly greater dental arch widths and
      lengths. The group with bilateral condylar affection had significantly decreased
      lower arch length and increased irregularity index (p < 0.035) compared to the
      non-affected group. CONCLUSIONS: Bilateral condylar involvement in children with
      JIA seems to reduce the lower arch length, while increasing the irregularity
      index of the lower front teeth.

PMID- 29464285
TI  - Revisiting the metabolic syndrome: the emerging role of aquaglyceroporins.
AB  - The metabolic syndrome (MetS) includes a group of medical conditions such as
      insulin resistance (IR), dyslipidemia and hypertension, all associated with an
      increased risk for cardiovascular disease. Increased visceral and ectopic fat
      deposition are also key features in the development of IR and MetS, with
      pathophysiological sequels on adipose tissue, liver and muscle. The recent
      recognition of aquaporins (AQPs) involvement in adipose tissue homeostasis has
      opened new perspectives for research in this field. The members of the
      aquaglyceroporin subfamily are specific glycerol channels implicated in energy
      metabolism by facilitating glycerol outflow from adipose tissue and its systemic
      distribution and uptake by liver and muscle, unveiling these membrane channels as
      key players in lipid balance and energy homeostasis. Being involved in a variety
      of pathophysiological mechanisms including IR and obesity, AQPs are considered
      promising drug targets that may prompt novel therapeutic approaches for metabolic
      disorders such as MetS. This review addresses the interplay between adipose
      tissue, liver and muscle, which is the basis of the metabolic syndrome, and
      highlights the involvement of aquaglyceroporins in obesity and related
      pathologies and how their regulation in different organs contributes to the
      features of the metabolic syndrome.

PMID- 29464287
TI  - Insertion torque values and success rates for paramedian insertion of orthodontic
      mini-implants : A retrospective study.
AB  - OBJECTIVES: Orthodontic mini-implants (OMIs) are a reliable method to provide
      temporary orthodontic anchorage. We hypothesized that there is an optimal
      insertion torque (<10 Ncm) that can be used to ensure the success of self
      drilling OMIs in the paramedian region. PATIENTS AND METHODS: Included were 40
      (26 females, 14 males) consecutive patients requiring palatal skeletal anchorage.
      Mean age was 17.3 years (range 11.0-44.6 years) for female patients and 15.7
      years (range 10.6-36.9 years) for male patients. A total of 22 patients received
      a Beneslider according to Wilmes for the distalization of maxillary first molars,
      10 patients received a Mesialslider for the mesialization of maxillary first
      molars, and 8 patients received a bone-borne rapid palatal expansion (RPE)
      appliance. Torque values of 10-15 Ncm were recorded in 46.3% of the OMIs and 15
      20 Ncm in 35% of OMIs. OMIs that endured the orthodontic force applied for >=6
      months were considered as success. RESULTS: The overall success rate was 98.8%.
      No significant differences were found between insertion torque values with
      respect to the right and left sides, Jarabak's ratio, facial axis, and Frankfort
      to mandibular plane angle. There were no significant differences in the OMIs
      insertion torques with regard to the different appliances. No association was
      found between insertion torque and vertical skeletal morphology. CONCLUSION: With
      an overall success rate of 98.8%, the study hypothesis that greater insertion
      torque (>10 Ncm) will decrease the success rate and increase palatal OMI failure
      was rejected.

PMID- 29464288
TI  - Mandibular fossa morphology during therapy with a fixed functional orthodontic
      appliance : A magnetic resonance imaging study.
AB  - OBJECTIVE: During therapy of distoclusion entailing a rigid, fixed orthodontic
      appliance, the mandibular fossa and condyle are ideally remodeled, while
      dentoalveolar effects occur through adaptive mechanisms. Adaptive processes,
      especially in the fossa region, have not been adequately investigated. Our
      magnetic resonance imaging (MRI) investigation aimed to assess the effects of
      therapy with a functional mandibular advancer (FMA) on mandibular fossa
      morphology. PATIENTS AND METHODS: We monitored via MRI the therapeutic course of
      25 patients at three time points. Visual findings and metric assessments were
      carried out in the sagittal plane. Three-dimensional (3D) reconstructions of the
      joint structure of two exemplary patients were also made. RESULTS: Visual
      examinations of the MRI slices at the three time points revealed no changes in
      fossa shape in any of the 50 temporomandibular joints. Lateral comparisons showed
      that the morphology of the fossae of all 25 patients was identical. Metric
      analysis demonstrated no significant alterations in width, depth, or in their
      ratio, not even laterally. Nine measurements of the distances between the porion,
      mandibular fossa, and articular eminence revealed no significant changes in total
      or on the left and right sides, or intralaterally. CONCLUSION: The visual
      findings and metric analyses of parasagittal MRI slices did not indicate any
      morphological changes in the mandibular fossa or articular eminence in patients
      with distoclusion treated via a rigid, fixed orthodontic appliance. However,
      special reworking of the MRI data facilitated reconstruction of the surfaces of
      joint structures in 3D. This new method makes it possible to depict more
      accurately and noninvasively the adaptive mechanisms not ascertainable via metric
      methods and to assess them as 3D structures.

PMID- 29464289
TI  - Long-term effects of Class II orthodontic treatment on oral health.
AB  - AIM: To investigate the long-term (>=15 years) benefit of orthodontic Class II
      treatment (Tx) on oral health (OH). SUBJECTS AND METHODS: All patients
      (Department of Orthodontics, University of Giessen, Giessen, Germany) who
      underwent Class II correction (Herbst-multibracket Tx, end of active Tx >= 15
      years ago) and agreed to participate in a recall (clinical examination,
      interview, impressions, and photographs) were included. Records after active Tx
      were used to assess the long-term OH effects. Data were compared to corresponding
      population-representative age-cohorts as well as to untreated Class I controls
      without orthodontic Tx need during adolescence. RESULTS: Of 152 treated Class II
      patients, 75 could be located and agreed to participate at 33.7 +/- 3.0 years of
      age (pre-Tx age: 14.0 +/- 2.7 years). The majority (70.8%) were fully satisfied
      with their teeth and with their masticatory system. The Decayed, Missing, Filled
      Teeth Index (DMFT) was 7.1 +/- 4.8 and, thus, almost identical to that of the
      untreated Class I controls (7.9 +/- 3.6). In contrast, the DMFT in the population
      representative age-cohort was 56% higher. The determined mean Community
      Periodontal Index (CPI) maximum score (1.6 +/- 0.6) was also comparable to the
      untreated Class I controls (1.7 +/- 0.9) but in the corresponding population
      representative age-cohort it was 19-44% higher. The extent of lower incisor
      gingival recessions did not differ significantly between the treated Class II
      participants and the untreated Class I controls (0.1 +/- 0.2 vs. 0.0 +/- 0.1 mm).
      CONCLUSION: Patients with orthodontically treated severe Class II malocclusions
      had a lower risk for oral health impairment than the general population. The risk
      corresponded to that of untreated Class I controls (without orthodontic Tx need
      during adolescence).

PMID- 29464291
TI  - [Rupture of the scapholunate intercarpal ligament].
AB  - Complete rupture of the scapholunate (SL) ligament can cause a dissociative
      carpal instability (CID). These ligamentous lesions are caused by a fall from a
      limited height of approximately 1 m or a fall, e. g. when playing handball or
      soccer. For a freshly injured wrist joint, the X-ray signs of a static
      instability (after excluding a fracture) are a SL distance >=3 mm, a SL angle >60
      degrees , and a dorsal displacement of the proximal scaphoid pole. Dynamic
      instabilities are best seen in kinematography of the wrist joint. Early ligament
      refixation is mandatory, ideally done in the first week after the incident or at
      least within the first 3 weeks. The cornerstone of the procedure is an anatomic
      reduction of the SL joint stabilized with K-wires for 8 weeks. In older lesions,
      ligament transfer or ligamentoplasty using a tendon transfer may add to stability
      but have so far not achieved a reliable joint alignment despite usually good
      functional results. It appears that the reduction of the proximal scaphoid pole
      deserves more attention.

PMID- 29464290
TI  - Does orthodontic treatment have a permanent effect on tooth color? : A systematic
      review and meta-analysis.
AB  - OBJECTIVES: Aim of this systematic review was to assess the effect of orthodontic
      treatment with fixed appliances on the tooth color of patients. METHODS: Nine
      databases were searched up to May 2017 for clinical cohort studies on the effect
      of fixed appliance treatment on tooth color. After elimination of duplicate
      studies, data extraction, and risk of bias assessment according to the Cochrane
      guidelines, random effects meta-analyses of mean differences (MD) or means and
      their 95% confidence intervals (CIs) were performed, followed by GRADE (Grading
      of Recommendations Assessment, Development and Evaluation) assessment of the
      quality of evidence. RESULTS: Three nonrandomized and one randomized study with a
      total of 138 patients (46% male, 54% female) with average age of 15.7 years were
      included. Tooth color of treated patients was significantly altered during or
      after orthodontic treatment (4 studies; average of 3.2 ?E units; 95% CI = 2.0-4.4
      ?E units), which was more than the variation among controls (1 study; MD = 1.9 ?E
      units; 95% CI = 1.7-2.2 ?E units). However, the quality of evidence was very low,
      due to the inclusion of nonrandomized studies, bias, and imprecision. Re-analysis
      of raw study data indicated that significant differences in clinically
      discernable treatment-induced color changes were seen between chemically and
      light-cured adhesives and among the various tooth categories. CONCLUSION:
      Existing evidence of very low quality indicates that orthodontic treatment might
      be associated with alterations of tooth color, which are however not consistently
      clinically discernible. Treatment-induced color alterations might be dependent on
      bonding material and tooth type, but evidence supporting this is weak.

PMID- 29464292
TI  - [Display technologies for augmented reality in medical applications].
AB  - BACKGROUND: One of the main challenges for modern surgery is the effective use of
      the many available imaging modalities and diagnostic methods. Augmented reality
      systems can be used in the future to blend patient and planning information into
      the view of surgeons, which can improve the efficiency and safety of
      interventions. OBJECTIVE: In this article we present five visualization methods
      to integrate augmented reality displays into medical procedures and the
      advantages and disadvantages are explained. MATERIAL AND METHODS: Based on an
      extensive literature review the various existing approaches for integration of
      augmented reality displays into medical procedures are divided into five
      categories and the most important research results for each approach are
      presented. RESULTS: A large number of mixed and augmented reality solutions for
      medical interventions have been developed as research prototypes; however, only
      very few systems have been tested on patients. CONCLUSION: In order to integrate
      mixed and augmented reality displays into medical practice, highly specialized
      solutions need to be developed. Such systems must comply with the requirements
      with respect to accuracy, fidelity, ergonomics and seamless integration into the
      surgical workflow.

PMID- 29464293
TI  - [Kirschner wire osteosynthesis for fractures in childhood: bury wires or not? :
      Results of a survey on care reality in Germany].
AB  - INTRODUCTION: Kirschner wire osteosynthesis is considered to be the standard
      technique for surgical fixation of displaced supracondylar humeral and distal
      radial fractures in children. The Kirschner wires can be left exposed or buried
      under the skin. Advantages of the epicutaneous technique are, e. g. the
      efficiency (cost, effort) and the possibility for wire removal without the
      necessity of a second anesthesia. On the other hand, there is a concern about
      higher infection rates as well as traumatization of the children due to
      externally visible wires. METHODS: A web-based survey of members of the DGU,
      DGOU, DGOOC, and the pediatric traumatology section of the DGU (SKT) was
      performed to evaluate current treatment concepts in Germany. The pros and cons
      for each technique were recorded and the need for a clinical study was examined.
      In addition, a cost analysis was performed for both methods. The results from the
      literature are summarized and discussed. RESULTS: A total of 710 questionnaires
      were evaluated. The majority of the respondents were trauma surgeons working in a
      hospital (80%). The buried technique was superior in both fracture groups
      (supracondylar humeral fractures 73% and distal radius fractures 69%), whereas a
      relevant difference could be found depending on the profession. The main reason
      for the subcutaneous technique was anxiety or observed higher infections using
      the epicutaneous technique. CONCLUSION: In Germany, the majority of wires are
      buried under the skin due to a fear of higher infection rates. In addition, other
      influencing factors such as pain and traditional approaches play a significant
      role. With respect to the results in the literature as well as a possible
      improvement of efficiency and avoidance of a second anesthesia, a multicentric
      clinical study seems necessary in the future to compare both techniques.

PMID- 29464294
TI  - [Defect coverage of fingers and thumb : Indications and treatment].
AB  - Due to the exposure of the hands in the daily routine, defect wounds of the hand
      are common. The injury severity varies and ranges from small fingertip defects to
      large soft tissue lesions with exposed tendons, nerves and vessels. The complete
      extent of the soft tissue defect is often only recognizable after meticulous
      debridement. A considerable variety of techniques for defect coverage are
      available to the surgeon but the actual challenge is to select the most
      appropriate procedure which will result in the smallest possible residual defect.
      This review article presents the diagnostic approaches to soft tissue defects of
      the hand and current treatment options.

PMID- 29464295
TI  - [Evolution and principles of intramedullary locked nailing].
AB  - Key factors for successful osteosynthetic fracture stabilization are anatomical
      fracture reduction, restoration of axis and torsion alignment as well as tissue
      preserving operative techniques. In long bone fractures, the use of
      intramedullary long bridging nailing offers ideal conditions for bone healing, as
      axial and rotational stability is provided by canal-filling nails and locking
      screws. In addition, the tissue in the fracture region is protected as the
      intramedullary nail insertion is distant from the fracture. The indication
      spectrum for modern intramedullary locked nailing includes diaphyseal fractures
      of long bones, metaphyseal fractures and reconstructions, as well as treatment of
      nonunion, osteotomy and arthrodesis of the lower extremities. Continuous
      improvements in nail design and instrumentation as well as the introduction of
      anatomical reconstruction nails will optimize the spectrum and effectiveness of
      intramedullary osteosynthesis even further.

PMID- 29464296
TI  - [A scaphoid fracture overlooked in CT in a combination injury of the wrist].
AB  - A case of a patient with a combined wrist injury is presented, where a scaphoid
      fracture was overlooked in the computed tomography scan. The case emphasizes the
      value of the x-ray control in ulnar abduction for all wrist lesions which need to
      be operatively stabilized.

PMID- 29464297
TI  - Correction to: External confirmation and exploration of the Kigali modification
      for diagnosing moderate or severe ARDS.
AB  - In Table 1 of this article, the numerical data were correct but the graphic part
      was imprecise.

PMID- 29464299
TI  - Burnout, boreout and compassion fatigue on the ICU: it is not about work stress,
      but about lack of existential significance and professional performance.

PMID- 29464298
TI  - Correction to: Catheter retention as a consequence rather than a cause of
      unfavorable outcome in candidemia.
AB  - In the original publication the members of the FUNGINOS network were provided in
      such a way that they could not be indexed as collaborators on PubMed.

PMID- 29464300
TI  - Association between vaginal parity and rectocele.
AB  - INTRODUCTION AND HYPOTHESIS: Rectocele is common in parous women but also seen in
      nulliparae. This study was designed to investigate the association between
      vaginal parity and descent of the rectal ampulla/rectocele depth as determined by
      translabial ultrasound (TLUS). METHODS: This retrospective observational study
      involved 1296 women seen in a urogynaecological centre. All had undergone an
      interview, clinical examination and 4D ultrasound (US) imaging supine and after
      voiding. Offline analysis of volume data was undertaken blinded against other
      data. Rectal ampulla position and rectocele depth were measured on Valsalva. A
      pocket depth of 10 mm was used as a cutoff to define rectocele on imaging.
      RESULTS: Most women presented with prolapse (53%, n = 686); 810 (63%) complained
      of obstructed defecation (OD). Clinically, 53% (n = 690) had posterior
      compartment prolapse with a mean Bp of -1 [standard deviation (SD)1.5; -3 to 9
      cm]. Mean descent of the rectal ampulla was 10 mm below the symphysis (SD 15.8; 
      50 to 41). A rectocele on imaging was found in 48% (n = 618). On univariate
      analysis, OD symptoms were strongly associated with rectal descent, rectocele
      depth and rectocele on imaging (all P < 0.001). The prevalence of a rectocele
      seen on imaging increased with vaginal parity (P < 0.001). One-way analysis of
      variance (ANOVA) of vaginal parity against rectal descent and rectocele depth
      showed a dose-response relationship (both P < 0.001). CONCLUSIONS: Vaginal parity
      was strongly associated with descent of the rectal ampulla and rectocele depth.
      This relationship approximated dose-response characteristics, with the greatest
      effect due to the first vaginal delivery.

PMID- 29464301
TI  - Outcomes of minimally invasive abdominal sacrocolpopexy with resident operative
      involvement.
AB  - INTRODUCTION AND HYPOTHESIS: Resident involvement in complex surgeries is under
      scrutiny with increasing attention paid to health care efficiency and quality.
      Outcomes of urogynecological surgery with resident involvement are poorly
      described. We hypothesized that resident surgical involvement does not influence
      perioperative outcomes in minimally invasive abdominal sacrocolpopexy (ASC).
      METHODS: Using the 2006-2012 National Surgical Quality Improvement Program
      database, we identified 450 cases of laparoscopic or robotic ASC performed with
      resident involvement. Resident operative participation was stratified by
      experience (junior [PGY 1-3] vs senior level [PGY >=4]). The primary outcome was
      operative time, and multinomial logistic regression was used to determine the
      effects of resident involvement and experience. Chi-squared analyses were used to
      assess the relationship between resident participation with length of stay (LOS)
      and 30-day complications and readmissions. RESULTS: Residents participated in 74%
      (n = 334) of these surgeries, and these cases were significantly longer (median
      220 vs 195 min, p = 0.03). On multivariate analysis, senior level resident
      involvement was associated with longer operative times across all time intervals
      compared with <2 h (2 to <=4 h relative risk reduction [RRR] 4.1, p = 0.007, CI
      1.47-11.40; 4 to <=6 h RRR 6.6, p = 0.001, CI 2.23-19.44; >=6 h RRR 4.7, p =
      0.020, CI 1.28-17.43). Resident participation was not associated with LOS,
      readmissions, or complications. CONCLUSIONS: Senior level resident involvement in
      minimally invasive ASC is associated with longer operative times, with no
      association with LOS or adverse perioperative outcomes. The educational benefit
      of surgical training does not adversely affect patient outcomes for ASC.

PMID- 29464303
TI  - Brief ethanol exposure and stress-related factors disorganize neonatal breathing
      plasticity during the brain growth spurt period in the rat.
AB  - RATIONALE: The effects of early ethanol exposure upon neonatal respiratory
      plasticity have received progressive attention given a multifactorial perspective
      related with sudden infant death syndrome or hypoxia-associated syndromes. The
      present preclinical study was performed in 3-9-day-old pups, a stage in
      development characterized by a brain growth spurt that partially overlaps with
      the 3rd human gestational trimester. METHODS: Breathing frequencies and apneas
      were examined in pups receiving vehicle or a relatively moderate ethanol dose
      (2.0 g/kg) utilizing a whole body plethysmograph. The experimental design also
      considered possible associations between drug administration stress and
      exteroceptive cues (plethysmographic context or an artificial odor). Ethanol
      exposure progressively exerted a detrimental effect upon breathing frequencies. A
      test conducted at PD9 when pups were under the state of sobriety confirmed
      ethanol's detrimental effects upon respiratory plasticity (breathing depression).
      RESULTS: Pre-exposure to the drug also resulted in a highly disorganized
      respiratory response following a hypoxic event, i.e., heightened apneic episodes.
      Associative processes involving drug administration procedures and placement in
      the plethysmographic context also affected respiratory plasticity. Pups that
      experienced intragastric administrations in close temporal contiguity with such a
      context showed diminished hyperventilation during hypoxia. In a 2nd test
      conducted at PD9 while pups were intoxicated and undergoing hypoxia, an
      attenuated hyperventilatory response was observed. In this test, there were also
      indications that prior ethanol exposure depressed breathing frequencies during
      hypoxia and a recovery normoxia phase. CONCLUSION: As a whole, the results
      demonstrated that brief ethanol experience and stress-related factors
      significantly disorganize respiratory patterns as well as arousal responses
      linked to hypoxia in neonatal rats.

PMID- 29464304
TI  - [Laparoscopic vs. open resection of colorectal liver metastases].

PMID- 29464302
TI  - Nicotine drug discrimination and nicotinic acetylcholine receptors in
      differentially reared rats.
AB  - RATIONALE: Individuals vary in sensitivity to the behavioral effects of nicotine,
      resulting in differences in vulnerability to nicotine addiction. The role of
      rearing environment in determining individual sensitivity to nicotine is unclear.
      The neuropharmacological mechanisms mediating the effect of rearing environment
      on the behavioral actions of nicotine are also poorly understood. OBJECTIVES: The
      contribution of rearing environment in determining the sensitivity to the
      interoceptive effects of nicotine was determined in rats reared in isolated
      conditions (IC) or enriched conditions (EC). The role of dopamine receptors and
      alpha4beta2*-nicotinic acetylcholine (nACh) receptors in mediating the
      differential effect of IC and EC on the interoceptive action of nicotine was
      determined. METHODS: The interoceptive action of nicotine was measured as the
      discriminative stimulus effect of nicotine. Mecamylamine- and eticlopride
      inhibition of the nicotine stimulus were used to examine nACh and dopamine
      receptors, respectively. alpha4beta2*-nACh receptor expression in the mesolimbic
      dopamine pathway was determined by quantitative autoradiography of [125I]
      epibatidine binding. RESULTS: EC-reared rats are less sensitive than IC-reared
      rats to the discriminative stimulus effects of nicotine at all but maximally
      effective doses. Mecamylamine inhibited the nicotine stimulus threefold more
      potently in EC-reared rats (IC50 = 0.25 mg/kg) compared to IC-reared rats (IC50 =
      0.75 mg/kg); eticlopride inhibition was not different. [125I]-epibatidine binding
      in the ventral tegmental area of EC-reared rats was reduced (2.8 +/- 0.3 fmol)
      compared to that of IC-reared rats (4.0 +/- 0.4 fmol); there was no difference in
      the nucleus accumbens. CONCLUSIONS: Rearing environment regulates the sensitivity
      to the interoceptive effects of nicotine and alpha4beta2*-nACh receptor
      expression in the mesolimbic dopamine pathway.

PMID- 29464305
TI  - [Rectal cancer surgery: robotic or laparoscopic?]

PMID- 29464306
TI  - [Surgical aspects of neuroendocrine tumors of the small intestine].
AB  - Neuroendocrine tumors of the small intestines are a rare disease with an
      incidence of 1 per 100,000 of the population; however, they account for over 20%
      of all neuroendocrine tumors and are the most common malignancy of the small
      intestines. Diagnosis is often made at a late stage of the disease, as the
      clinical symptoms are unspecific. Approximately one third of all patients show
      hepatic metastases at the time of diagnosis. There is no correlation between
      tumor size and tumor stage. Even small tumors <10 mm harbor the risk for
      lymphatic and distant metastases so that the extent of surgery is not determined
      by the size of the primary tumor. The intestinal-sparing resection with
      systematic lymphadenectomy along the superior mesenteric artery and removal of
      the retropancreatic lymph nodes is recommended even in localized stages of the
      disease.

PMID- 29464307
TI  - [Pathology of early stage cancer of the gastrointestinal tract : Definition,
      principles and diagnosis].
AB  - BACKGROUND: Early stage cancers of the gastrointestinal tract are malignant
      tumors that are eligible for local therapy regimens and show an excellent
      prognosis. OBJECTIVE: This article explains the histopathological aspects of the
      various diseases that are covered by this topic. METHODS: Organ-preserving
      therapies are discussed according to their locations and under consideration of
      the current guidelines and the relevant literature. RESULTS: The exact
      histopathological evaluation of early cancers of the gastrointestinal tract is of
      crucial importance. It is the essential basis for all further therapy decisions.
      In most cases, an option for a local resection is given. In comparison to partial
      or complete organ resections, local resection is associated with a significantly
      decreased morbidity and reduced length of hospital stays; however, it must be
      ensured that local therapies do not become responsible for increased rates of
      tumor recurrence and progression. Therefore, an optimal risk estimation based on
      a sophisticated histopathological classification is mandatory. This includes the
      evaluation of the infiltration depth, grading, lymphovascular invasion and
      resection margins. CONCLUSION: Molecular analyses have not yet entered clinical
      practice. The only exceptions are investigations to detect hereditary diseases.
      The exact histopathological diagnostic of early gastrointestinal cancers is the
      basis of an effective and organ-preserving therapy.

PMID- 29464308
TI  - [Intrahepatic cholangiocarcinoma : Results after 84 resections].
AB  - BACKGROUND: The incidence of intrahepatic cholangiocarcinoma (ICC) is increasing
      worldwide. Surgical resection is the only curative treatment option. AIM OF THE
      STUDY: This study analyzed the prognostic factors after resection of ICC.
      MATERIAL AND METHODS: A total of 84 patients were surgically treated under
      potentially curative intent. Perihilar and distal cholangiocarcinomas were
      excluded. The 5-year survival was analyzed with respect to tumor stage (TNM),
      number of lesions, complete surgical resection (R0), peritoneal carcinosis and
      postoperative complications. RESULTS: The 5-year survival was 27% and 77% of
      patients underwent R0 resections. In the univariate analysis a T stage >2, an N+
      situation or an R+ resection as well as peritoneal and multilocular intrahepatic
      spread were associated with a poorer prognosis. Postoperative complications also
      negatively influenced survival. On multivariate analysis the absence of
      peritoneal spread, node-negative tumor stages, singular hepatic lesions and a low
      T stage as well as the absence of complications were associated with improved
      survival. DISCUSSION: The prognosis of ICC is poor even after successful surgical
      resection. Well-known tumor characteristics such as TNM are relevant prognostic
      factors. Surgical resection is accompanied by postoperative complications (most
      frequently biliary), which negatively influence survival. Adjuvant strategies are
      urgently needed to improve long-term survival even after complete surgical
      resection.

PMID- 29464309
TI  - Nanotechnology in Plants.
AB  - The integration of nanotechnology in medicine has had a tremendous impact in the
      past few decades. The discovery of synthesis of nanomaterials (NMs) and their
      functions as versatile tools promoted various applications in nano-biotechnology
      and nanomedicine. Although the physical and chemical methods are still considered
      as commonly used methods, they introduce several drawbacks such as the use of
      toxic chemicals (solvent, reducing, and capping agents) and poor control of size,
      size distribution, and morphology, respectively. Additionally, the NMs
      synthesized in organic solvents and hydrophobic surfactants rapidly aggregate in
      aqueous solutions or under physiologic conditions, limiting their applications in
      medicine. Many of the phase-transfer strategies were developed and applied for
      the transfer of NMs into aqueous solutions. Although great efforts have been put
      into phase transfers, they mostly include expensive, time-consuming, intensive
      labor work, multi steps, and complicated procedures.Use of plant extracts in the
      biological synthesis method offers stark advantages over other biomolecules
      (protein, enzyme, peptide, and DNA). Plant extracts have been commonly used for
      food, medicine, NM synthesis, and biosensing. There are many viable techniques
      developed for the production of plant extracts with various contents based on
      their simplicity, cost, and the type of extract content. In this chapter, we
      conduct a comparative study for extract preparation techniques, the use of
      extracts for metallic single and hybrid nanoparticle (NP) synthesis, and their
      antimicrobial properties against pathogenic and plant-based bacteria. Graphical
      Abstract.

PMID- 29464310
TI  - Different strategies for multi-enzyme cascade reaction for chiral vic-1,2-diol
      production.
AB  - The stereoselective three-enzyme cascade for the one-pot synthesis of (1S,2S)-1
      phenylpropane-1,2-diol ((1S,2S)-1-PPD) from inexpensive starting substrates,
      benzaldehyde and acetaldehyde, was explored. By coupling stereoselective
      carboligation catalyzed by benzoylformate decarboxylase (BFD), L-selective
      reduction of a carbonyl group with alcohol dehydrogenase from Lactobacillus
      brevis (ADHLb) as well as the coenzyme regeneration by formate dehydrogenase
      (FDH), enantiomerically pure diastereoselective 1,2-diol was produced. Two
      different multi-enzyme system approaches were applied: the sequential two-step
      one-pot and the simultaneous one-pot cascade. All enzymes were kinetically
      characterized. The impact of acetaldehyde on the BFD and ADHLb stability was
      investigated. To overcome the kinetic limitation of acetaldehyde in the
      carboligation reaction and to reduce its influence on the enzyme stability,
      experiments were performed in two different excesses of acetaldehyde (100 and
      300%). Due to the ADHLb deactivation by acetaldehyde, the simultaneous one-pot
      cascade proved not to be the first choice for the investigated three-enzyme
      system. In the sequential cascade with 300% acetaldehyde excess a 100% yield of
      vic 1,2-diol was reached.

PMID- 29464311
TI  - High PD-L1 expression predicts poor prognosis in diffuse large B-cell lymphoma.

PMID- 29464312
TI  - High proportion of TAFRO syndrome in Thai adult Castleman's disease patients: a
      10-year experience.
AB  - Castleman's disease (CD) is a rare lymphoproliferative disorder, and its
      prevalence in Thailand is not known. This 10-year period study investigated the
      prevalence of CD in Thailand, and the clinical characteristics and outcomes of
      Thai CD patients, with special focus on the existence and prevalence of TAFRO
      syndrome. TAFRO syndrome is defined as CD with thrombocytopenia, anasarca, fever,
      reticulin fibrosis, and organomegaly. Thirty-three CD patients diagnosed and
      treated at Siriraj Hospital during January 2007 to December 2016 were included.
      The prevalence of CD was 1.4 per 1,000,000 patients/10 years. Median age was 46
      years, with slight female predominance. Six patients were assigned to the TAFRO
      group. A high proportion of TAFRO syndrome (18.2%) was found among Thai adult CD
      patients. In addition to routine TAFRO diagnostic criteria, significantly lower
      hemoglobin and albumin levels were observed in the TAFRO group than in the non
      TAFRO group. Treatment outcomes of CD patients were complete remission (52%),
      stable disease (30%), and death (13%). Three-year overall survival in the non
      TAFRO group and TAFRO group was 88 and 50%, respectively. While most CD patients
      had a good prognosis, severe cases with TAFRO syndrome had poor outcome.

PMID- 29464313
TI  - Nuclear, chloroplast, and mitochondrial data of a US cannabis DNA database.
AB  - As Cannabis sativa (marijuana) is a controlled substance in many parts of the
      world, the ability to track biogeographical origin of cannabis could provide law
      enforcement with investigative leads regarding its trade and distribution.
      Population substructure and inbreeding may cause cannabis plants to become more
      genetically related. This genetic relatedness can be helpful for intelligence
      purposes. Analysis of autosomal, chloroplast, and mitochondrial DNA allows for
      not only prediction of biogeographical origin of a plant but also discrimination
      between individual plants. A previously validated, 13-autosomal STR multiplex was
      used to genotype 510 samples. Samples were analyzed from four different sites: 21
      seizures at the US-Mexico border, Northeastern Brazil, hemp seeds purchased in
      the US, and the Araucania area of Chile. In addition, a previously reported multi
      loci system was modified and optimized to genotype five chloroplast and two
      mitochondrial markers. For this purpose, two methods were designed: a
      homopolymeric STR pentaplex and a SNP triplex with one chloroplast (Cscp001)
      marker shared by both methods for quality control. For successful mitochondrial
      and chloroplast typing, a novel real-time PCR quantitation method was developed
      and validated to accurately estimate the quantity of the chloroplast DNA (cpDNA)
      using a synthetic DNA standard. Moreover, a sequenced allelic ladder was also
      designed for accurate genotyping of the homopolymeric STR pentaplex. For
      autosomal typing, 356 unique profiles were generated from the 425 samples that
      yielded full STR profiles and 25 identical genotypes within seizures were
      observed. Phylogenetic analysis and case-to-case pairwise comparisons of 21
      seizures at the US-Mexico border, using the Fixation Index (F ST ) as genetic
      distance, revealed the genetic association of nine seizures that formed a
      reference population. For mitochondrial and chloroplast typing, subsampling was
      performed, and 134 samples were genotyped. Complete haplotypes (STRs and SNPs)
      were observed for 127 samples. As expected, extensive haplotype sharing was
      observed; five distinguishable haplotypes were detected. In the reference
      population, the same haplotype was observed 39 times and two unique haplotypes
      were also detected. Haplotype sharing was observed between the US border
      seizures, Brazil, and Chile, while the hemp samples generated a distinct
      haplotype. Phylogenetic analysis of the four populations was performed, and
      results revealed that both autosomal and lineage markers could discern population
      substructure.

PMID- 29464315
TI  - I don't need your attention: ostracism can narrow the cone of gaze.
AB  - Previous research has shown that ostracized participants seek inclusive cues,
      such as gaze directed at them, when trying to reaffiliate. However, instead of
      seeking reinclusion, ostracized individuals may sometimes withdraw from
      interactions if not offered an opportunity for reaffiliation. In the current
      study, after an ostracism manipulation with no reaffiliation opportunity,
      participants judged whether faces portraying direct gaze or slightly averted gaze
      (2 degrees -8 degrees  to the left and to the right) were looking at them or not.
      Compared to an inclusion group and a non-social control group, ostracized
      participants accepted a smaller range of gaze directions as being directed at
      them, i.e., they had a narrower "cone of gaze". The width of the gaze cone was
      equally wide in the inclusion and control groups. We propose that, without an
      opportunity for reaffiliation, ostracized participants may start to view other
      people as particularly unapproachable, possibly indicative of a motivational
      tendency to disengage from interactions.

PMID- 29464316
TI  - The right look for the job: decoding cognitive processes involved in the task
      from spatial eye-movement patterns.
AB  - The aim of the study was not only to demonstrate whether eye-movement-based task
      decoding was possible but also to investigate whether eye-movement patterns can
      be used to identify cognitive processes behind the tasks. We compared eye
      movement patterns elicited under different task conditions, with tasks differing
      systematically with regard to the types of cognitive processes involved in
      solving them. We used four tasks, differing along two dimensions: spatial (global
      vs. local) processing (Navon, Cognit Psychol, 9(3):353-383 1977) and semantic
      (deep vs. shallow) processing (Craik and Lockhart, J Verbal Learn Verbal Behav,
      11(6):671-684 1972). We used eye-movement patterns obtained from two time
      periods: fixation cross preceding the target stimulus and the target stimulus. We
      found significant effects of both spatial and semantic processing, but in case of
      the latter, the effect might be an artefact of insufficient task control. We
      found above chance task classification accuracy for both time periods: 51.4% for
      the period of stimulus presentation and 34.8% for the period of fixation cross
      presentation. Therefore, we show that task can be to some extent decoded from the
      preparatory eye-movements before the stimulus is displayed. This suggests that
      anticipatory eye-movements reflect the visual scanning strategy employed for the
      task at hand. Finally, this study also demonstrates that decoding is possible
      even from very scant eye-movement data similar to Coco and Keller, J Vis 14(3):11
      11 (2014). This means that task decoding is not limited to tasks that naturally
      take longer to perform and yield multi-second eye-movement recordings.

PMID- 29464314
TI  - Activation status of peripheral blood neutrophils and the complement system in
      adult rheumatoid arthritis patients undergoing combined therapy with infliximab
      and methotrexate.
AB  - We examined the functional activity of peripheral blood neutrophils and the
      complement system activation status in patients with rheumatoid arthritis (RA)
      undergoing infliximab/methotrexate combined therapy. We studied female RA
      patients under treatment with infliximab (3-5 mg/kg) and methotrexate (15-25
      mg/week) who presented inactive (i-RA; n = 34, DAS-28 <= 2.6) or at least
      moderately active disease (a-RA; n = 29, DAS-28 > 3.2), and age-matched healthy
      women (n = 38). We measured the levels of reactive oxygen species (ROS)
      generation (chemiluminescence assay) and membrane expression of FcgammaRIIa/CD32,
      FcgammaRIIIb/CD16, CR1/CD35, and CR3/CD11b receptors (ELISA assay) in
      neutrophils. We also determined the hemolytic activity of the alternative and
      classical pathways of the complement system (spectrophotometry), serum levels of
      C5a and Bb (ELISA assay), and serum chemotactic activity (Boyden chamber).
      Compared with the control group, i-RA and a-RA patients exhibited: (1) increased
      neutrophil ROS production and membrane expression of FcgammaRIIa/CD32,
      FcgammaRIIIb/CD16, and CR1/CD35, indicating neutrophil activation; and (2)
      increased serum chemotactic activity and decreased activity of the alternative
      complement pathway, indicating systemic complement system activation. The levels
      of C-reactive protein in a-RA patients were augmented, compared with i-RA
      patients. Although infliximab/methotrexate combined therapy induced disease
      remission according to the DAS-28 criteria, both i-RA and a-RA patients still
      exhibited significant levels of systemic activation of neutrophils and the
      complement system.

PMID- 29464318
TI  - Diffusion MRI-based cortical connectome reconstruction: dependency on
      tractography procedures and neuroanatomical characteristics.
AB  - Diffusion MRI (dMRI)-based tractography offers unique abilities to map whole
      brain structural connections in human and animal brains. However, dMRI-based
      tractography indirectly measures white matter tracts, with suboptimal accuracy
      and reliability. Recently, sophisticated methods including constrained spherical
      deconvolution (CSD) and global tractography have been developed to improve tract
      reconstructions through modeling of more complex fiber orientations. Our study
      aimed to determine the accuracy of connectome reconstruction for three dMRI-based
      tractography approaches: diffusion tensor (DT)-based, CSD-based and global
      tractography. Therefore, we validated whole brain structural connectome
      reconstructions based on ten ultrahigh-resolution dMRI rat brain scans and 106
      cortical regions, from which varying tractography parameters were compared
      against standardized neuronal tracer data. All tested tractography methods
      generated considerable numbers of false positive and false negative connections.
      There was a parameter range trade-off between sensitivity: 0.06-0.63
      interhemispherically and 0.22-0.86 intrahemispherically; and specificity: 0.99
      0.60 interhemispherically and 0.99-0.23 intrahemispherically. Furthermore,
      performance of all tractography methods decreased with increasing spatial
      distance between connected regions. Similar patterns and trade-offs were found,
      when we applied spherical deconvolution informed filtering of tractograms,
      streamline thresholding and group-based average network thresholding. Despite the
      potential of CSD-based and global tractography to handle complex fiber
      orientations at voxel level, reconstruction accuracy, especially for long
      distance connections, remains a challenge. Hence, connectome reconstruction
      benefits from varying parameter settings and combination of tractography methods
      to account for anatomical variation of neuronal pathways.

PMID- 29464319
TI  - Involvement of CAT in the detoxification of HT-induced ROS burst in rice anther
      and its relation to pollen fertility.
AB  - KEY MESSAGE: HT-induced ROS burst in developing anther is closely related to the
      lowered CAT activity as the result of the markedly suppressed OsCATB transcript,
      thereby causing severe fertility injury for rice plants exposed to HT at meiosis
      stage. The reproductive stage of rice plants is highly sensitive to heat stress.
      In this paper, different rice cultivars were used to investigate the relationship
      of HT-induced floret sterility with reactive oxygen species (ROS) detoxification
      in rice anthers under well-controlled climatic conditions. Results showed that
      high temperature (HT) exposure significantly enhanced the ROS level and
      malondialdehyde (MDA) content in developing anther, and the increase in ROS
      amount in rice anther under HT exposure was closely associated with HT-induced
      decline in the activities of several antioxidant enzymes. For various antioxidant
      enzymes, SOD and CAT were more susceptible to the ROS burst in rice anther
      induced by HT exposure than APX and POD, in which SOD and CAT activity in
      developing anther decreased significantly by HT exposure, whereas APX activity
      was relatively stable among different temperature regimes. HT-induced decrease in
      CAT activity was attributable to the suppressed transcript of OsCATB. This
      occurrence was strongly responsible for HT-induced increase in ROS level and
      oxidative-damage in rice anther, thereby it finally caused significant reduction
      in pollen viability and floret fertility for the rice plants exposed to HT during
      meiosis. Exogenous application of 1000 uM salicylic acid (SA) may alleviate HT
      induced reduction in pollen viability and floret fertility, concomitantly with
      the increased CAT activity and reduced ROS level in rice anther.

PMID- 29464320
TI  - Comparative immunohistochemical characterization of interstitial cells in the
      urinary bladder of human, guinea pig and pig.
AB  - Interstitial cells (ICs) are thought to play a functional role in urinary
      bladder. Animal models are commonly used to elucidate bladder physiology and
      pathophysiology. However, inter-species comparative studies on ICs are rare. We
      therefore analyzed ICs and their distribution in the upper lamina propria (ULP),
      the deeper lamina propria (DLP) and the detrusor muscular layer (DET) of human,
      guinea pig (GP) and pig. Paraffin slices were examined by immunohistochemistry
      and 3D confocal immunofluorescence of the mesenchymal intermediate filament
      vimentin (VIM), alpha-smooth muscle actin (alphaSMA), platelet-derived growth
      factor receptor alpha (PDGFRalpha) and transient receptor potential cation
      channel A1 (TRPA1). Image stacks were processed for analysis using Huygens
      software; quantitative analysis was performed with Fiji macros. ICs were
      identified by immunoreactivity for VIM (excluding blood vessels). In all species
      >= 75% of ULP ICs were VIM+/PDGFRalpha+ and >= 90% were VIM+/TRPA1+. In human and
      pig >= 74% of ULP ICs were VIM+/alphaSMA+, while in GP the percentage differed
      significantly with only 37% VIM+/alphaSMA+ ICs. Additionally, over 90% of
      alphaSMA+ ICs were also TRPA1+ and PDGFRalpha+ in human, GP and pig. In all three
      species, TRPA1+ and PDGFRalpha+ ICs point to an active role for these cells in
      bladder physiology, regarding afferent signaling processes and signal
      modification. We hypothesize that decline in alphaSMA-positivity in GP reflects
      adaptation of bladder histology to smaller bladder size. In our experiments, pig
      bladder proved to be highly comparable to human urinary bladder and seems to
      provide safer interpretation of experimental findings than GP.

PMID- 29464321
TI  - Origin and development of septoclasts in endochondral ossification of mice.
AB  - Septoclasts are mononuclear spindle-shaped phagocytes with their long processes
      in uncalcified cartilage matrices and locate adjacent to the capillary
      endothelium at the chondro-osseous junction of the growth plate. We have
      previously revealed a selective expression of epidermal-type fatty acid-binding
      protein (E-FABP/FABP5) in septoclasts. Although, pericytes are known to
      distribute along capillaries and directly surround their endothelial cells in a
      situation similar to septoclasts, no clear evidence is available on the
      relationship between septoclasts and pericytes. We investigated the chronological
      localization and morphological change of septoclasts during development of the
      tibia of mice to clarify the development of septoclasts and the immune
      localization of pericyte markers in septoclasts to clarify the origin of
      septoclasts. E-FABP-immunoreactive septoclasts emerged at the perichondrium in
      the middle of the cartilaginous templates of the tibia in prenatal development.
      Septoclasts migrated to the surface of the cartilage adjacent to invading blood
      vessels. Processes of septoclasts became longer and their apexes attached to Von
      Kossa-negative uncalcified matrices during the formation process of the primary
      ossification center. Not only platelet-derived growth factor receptor beta, but
      also neuron-glial antigen 2 was localized in septoclasts of mice from E15
      (embryonic day 15) to P6w (postnatal 6 week). Our results suggest that
      septoclasts are originated from pericytes and involved in the blood vessel
      invasion during formation of the primary ossification center.

PMID- 29464323
TI  - Vermetid gastropods modify physical and chemical conditions above coral-algal
      interactions.
AB  - Interaction modifications can arise when a third species alters the physical and
      chemical environment within which two other species interact. On coral reefs,
      corals and algae commonly interact amid a suite of other species that may modify
      their interaction. Massive Porites coral and algal turfs often are covered by
      mucus nets cast by the vermetid gastropod, Ceraesignum maximum. Previously,
      vermetid mucus nets have been shown to have deleterious effects on corals. Here,
      we hypothesized that vermetids not only have direct effects on coral, but they
      also change the local physical and chemical environment establishing the
      potential for interaction modifications by intensifying the effects of algae on
      corals. To test this, we examined the effect of vermetids on physical and
      chemical aspects of the environments. We quantified light penetration, water
      flow, diffusive boundary layer (DBL) thickness, and oxygen concentrations in the
      presence and absence of vermetid nets. Vermetid nets did not affect light levels.
      Because we observed reduced water flow and increased DBL thickness in the
      presence of nets, we also expected to observe high oxygen concentration over
      coral surfaces. Instead, we observed no difference in oxygen concentrations in
      the presence of mucus nets. To explain the lower than expected oxygen
      concentrations, we hypothesize that nets decreased photosynthesis and/or
      increased respiration of corals and algae and their associated microbiota. This
      is the first study to explore mechanisms underlying the deleterious effects of
      vermetids on corals, and shows that vermetid mucus nets may modify coral-algal
      interactions by intensifying physical and chemical conditions.

PMID- 29464322
TI  - Voltinism-associated differences in winter survival across latitudes: integrating
      growth, physiology, and food intake.
AB  - Species that span large latitudinal gradients face strong differences in
      voltinism and in winter conditions within their range. Latitudinal gradients in
      winter survival and especially their underlying mechanisms and association with
      voltinism patterns are poorly studied. We tested in the damselfly Enallagma
      cyathigerum whether high-latitude populations were better in dealing with the
      longer winters compared to central- and low-latitude populations and whether this
      was associated with changes in voltinism. We thereby evaluated whether higher
      initial levels and/or lower reductions during winter of energy storage (measured
      as fat content) and investment in immune function [measured as the activity of
      phenoloxidase (PO)], and/or stronger compensatory responses in food intake
      contributed to the higher winter survival in high-latitude populations. To this
      end, we simulated a long high-latitude winter at 4  degrees C under manipulated
      food conditions. Across food levels, winter survival was highest in Swedish
      larvae, intermediate in Belgian larvae, and lowest in Spanish larvae, indicating
      latitude-specific thermal adaptation that could be partly linked to differences
      in voltinism. The semi-voltine Swedish larvae were growing slower before winter
      and as a result accumulated the highest fat content and PO activity when the
      winter started compared to the univoltine, faster growing Belgian, and Spanish
      larvae. Fat content and PO activity declined during the winter, yet equally
      across latitudes, and were not buffered by compensatory food intake. Our data
      identified possible underlying physiological mechanisms of winter survival and
      support the hypothesis that widespread latitude-associated voltinism shifts may
      be a selective factor contributing to latitudinal shifts in winter survival.

PMID- 29464324
TI  - Combining evolutionary and metabolic engineering in Rhodosporidium toruloides for
      lipid production with non-detoxified wheat straw hydrolysates.
AB  - Improving the yield of carbohydrate to lipid conversion and lipid productivity
      are two critical goals to develop an economically feasible process to
      commercialize microbial oils. Lignocellulosic sugars are potential low-cost
      carbon sources for this process but their use is limited by the toxic compounds
      produced during biomass pretreatment at high solids loading, and by the pentose
      sugars (mainly xylose) which are not efficiently metabolized by many
      microorganisms. Adaptive laboratory evolution was used to select a Rhodosporidium
      toruloides strain with robust growth in non-detoxified wheat straw hydrolysates,
      produced at 20% solids loading, and better xylose consumption rate. An arabinose
      inducible cre-lox recombination system was developed in this evolved strain that
      was further engineered to express a second copy of the native DGAT1 and SCD1
      genes under control of the native xylose reductase (XYL1) promoter. Fed-batch
      cultivation of the engineered strain in 7-L bioreactors produced 39.5 g lipid/L
      at a rate of 0.334 g/Lh-1 and 0.179 g/g yield, the best results reported in R.
      toruloides with non-detoxified lignocellulosic hydrolysates to date.

PMID- 29464325
TI  - Detection and cell sorting of Pseudonocardia species by fluorescence in situ
      hybridization and flow cytometry using 16S rRNA-targeted oligonucleotide probes.
AB  - Pseudonocardia spp. are receiving increasing attention due to their ability to
      biodegrade recalcitrant cyclic ether pollutants (e.g., 1,4-dioxane and
      tetrahydrofuran), as well as for their distinctive ecological niches (e.g.,
      symbiosis with ants/plants and production of antibiotics). Isolating and
      characterizing Pseudonocardia spp. is thus important to discern their metabolic
      and physiological idiosyncrasies and advance their potential applications.
      However, slow growth, low cell yield, and dissimilar colony morphology hinder
      efficient isolation of Pseudonocardia using conventional plating methods. Here,
      we develop the first fluorescent probe (Pse631) targeting the 16S rRNA of
      Pseudonocardia members. In combination with flow cytometry and cell sorting, in
      situ hybridization with this probe enables sensitive and specific detection of
      Pseudonocardia cells in mixed cultures and enriched environmental samples without
      significant false positives, using Escherichia coli, Bacillus subtilis, and
      Mycobacterium spp. as negative controls. Pseudonocardia dioxanivorans CB1190
      cells labeled with Pse631 as a positive control were detected when their relative
      abundance in the total bacterial community was as low as 0.1%. Effective
      separation of Pseudonocardia cells from the mixed consortium was confirmed by
      quantitative PCR analysis of sorted cells. This study provides a culture
      independent high-throughput molecular approach enabling effective separation of
      Pseudonocardia populations from complex microbial communities. This approach will
      not only facilitate subsequent molecular analyses including species
      identification and quantification, but also advance understanding of their
      catabolic capacities and functional molecular diversity.

PMID- 29464326
TI  - Furfural-tolerant Zymomonas mobilis derived from error-prone PCR-based whole
      genome shuffling and their tolerant mechanism.
AB  - Furfural-tolerant strain is essential for the fermentative production of biofuels
      or chemicals from lignocellulosic biomass. In this study, Zymomonas mobilis CP4
      was for the first time subjected to error-prone PCR-based whole genome shuffling,
      and the resulting mutants F211 and F27 that could tolerate 3 g/L furfural were
      obtained. The mutant F211 under various furfural stress conditions could rapidly
      grow when the furfural concentration reduced to 1 g/L. Meanwhile, the two mutants
      also showed higher tolerance to high concentration of glucose than the control
      strain CP4. Genome resequencing revealed that the F211 and F27 had 12 and 13
      single-nucleotide polymorphisms. The activity assay demonstrated that the
      activity of NADH-dependent furfural reductase in mutant F211 and CP4 was all
      increased under furfural stress, and the activity peaked earlier in mutant than
      in control. Also, furfural level in the culture of F211 was also more rapidly
      decreased. These indicate that the increase in furfural tolerance of the mutants
      may be resulted from the enhanced NADH-dependent furfural reductase activity
      during early log phase, which could lead to an accelerated furfural
      detoxification process in mutants. In all, we obtained Z. mobilis mutants with
      enhanced furfural and high concentration of glucose tolerance, and provided
      valuable clues for the mechanism of furfural tolerance and strain development.

PMID- 29464328
TI  - Correction to: Epidural Balloon Placement for Protection of the Spinal Canal
      During Cryoablation of Paraspinal Lesions.
AB  - In the published article the first sentence under the section heading Case
      Reports ("This study was conducted with the institutional review board approval
      and complied with the Health Insurance Portability and Accountability Act.") is
      incorrect. That sentence should be replaced with: "Case reports are exempt from
      IRB approval at the authors' institution. This study complied with the Health
      Insurance Portability and Accountability Act."

PMID- 29464327
TI  - Unclassified sclerosing malignant melanomas with AKAP9-BRAF gene fusion: a report
      of two cases and review of BRAF fusions in melanocytic tumors.
AB  - The current classification of melanocytic tumors includes clinical, pathological,
      and molecular data. A subset of lesions remains difficult to classify according
      to these complex multilayer schemes. We report two cases of deeply infiltrating
      melanomas with a sclerosing background. The first case occurred on the back of a
      middle-aged man appearing clinically as a dermatofibroma. The architectural and
      cytological aspects resembled those of a desmoplastic melanoma but the strong
      expression of both melanA and HMB45, two stainings usually reported as negative
      in this entity, raised the question of an alternate diagnosis. The second case
      was a large, slowly growing, perivulvar tumor in a middle-aged woman. The
      morphology was complex with a central junctional spitzoid pattern associating an
      epidermal hyperplasia with large nests of large spindled melanocytes. The dermal
      component was made of deeply invasive strands and nests of nevoid unpigmented
      melanocytes surrounded by fibrosis; a perineural invasion was present at the
      periphery of the lesion. In both cases, aCGH found, among many other anomalies, a
      chromosomal breakpoint at the BRAF locus. RNA sequencing identified in both an
      AKAP9-BRAF gene fusion. A complementary resection was performed and no relapses
      have been observed in the respectively 15 and 6 months of follow-up. Both of
      these melanomas remained unclassified. We further review the variety of
      melanocytic tumors associated with such BRAF fusions.

PMID- 29464329
TI  - [Systematic literature search in PubMed : A short introduction].
AB  - In order to identify current (and relevant) evidence for a specific clinical
      question within the unmanageable amount of information available, solid skills in
      performing a systematic literature search are essential. An efficient approach is
      to search a biomedical database containing relevant literature citations of study
      reports. The best known database is MEDLINE, which is searchable for free via the
      PubMed interface. In this article, we explain step by step how to perform a
      systematic literature search via PubMed by means of an example research question
      in the field of ophthalmology. First, we demonstrate how to translate the
      clinical problem into a well-framed and searchable research question, how to
      identify relevant search terms and how to conduct a text word search and a search
      with keywords in medical subject headings (MeSH) terms. We then show how to limit
      the number of search results if the search yields too many irrelevant hits and
      how to increase the number in the case of too few citations. Finally, we
      summarize all essential principles that guide a literature search via PubMed.

PMID- 29464330
TI  - The interplay of histone H2B ubiquitination with budding and fission yeast
      heterochromatin.
AB  - Mono-ubiquitinated histone H2B (H2B-Ub) is important for chromatin regulation of
      transcription, chromatin assembly, and also influences heterochromatin. In this
      review, we discuss the effects of H2B-Ub from nucleosome to higher-order
      chromatin structure. We then assess what is currently known of the role of H2B-Ub
      in heterochromatic silencing in budding and fission yeasts (S. cerevisiae and S.
      pombe), which have distinct silencing mechanisms. In budding yeast, the SIR
      complex initiates heterochromatin assembly with the aid of a H2B-Ub
      deubiquitinase, Ubp10. In fission yeast, the RNAi-dependent pathway initiates
      heterochromatin in the context of low H2B-Ub. We examine how the different
      silencing machineries overcome the challenge of H2B-Ub chromatin and highlight
      the importance of using these microorganisms to further our understanding of H2B
      Ub in heterochromatic silencing pathways.

PMID- 29464331
TI  - Salvage proton beam therapy for recurrent iris melanoma: outcome and side
      effects.
AB  - PURPOSE: This study aims to analyze the effect of salvage proton beam therapy for
      the treatment of recurrent iris melanoma. METHOD: In this clinical case series,
      we retrospectively analyzed the data of eight patients who underwent proton beam
      therapy of the whole anterior segment as salvage therapy between 2000 and 2016
      for recurrent iris melanoma after resection, ruthenium brachytherapy, or sector
      proton beam therapy. Two patients received salvage proton beam therapy for
      repeated tumor relapse. All patients were observed and prepared for proton beam
      therapy at the Charite and irradiated at the Helmholtz-Zentrum Berlin where they
      received 50 cobalt Gray equivalents (CGE) in four daily fractions. We
      investigated survival rates and ocular outcome. RESULTS: Median follow-up after
      salvage proton beam therapy was 39 months. No local recurrence was detected
      during follow-up. One patient died from hepatic metastases 5.5 years after
      salvage therapy. Secondary glaucoma occurred in seven out of eight patients
      during follow-up. Two patients had chronic corneal erosion and two other patients
      presented with corneal decompensation, necessitating Descemet membrane
      endothelial keratoplasty (DMEK), and perforating keratoplasty. Median visual
      acuity was 0.2 logMAR before salvage proton beam therapy and 0.7 logMAR at the
      end of follow-up. CONCLUSION: Whole anterior segment salvage proton beam therapy
      has effectively controlled recurrent iris melanoma in our patients, but has been
      associated with a high incidence of radiation-induced corneal impairment and
      secondary glaucoma requiring extensive secondary treatment.

PMID- 29464332
TI  - The effect of sevoflurane on retinal angiogenesis in a mouse model of oxygen
      induced retinopathy.
AB  - BACKGROUND: Sevoflurane is commonly used in general anesthesia for premature
      neonates. The main mechanism of retinopathy of prematurity (ROP) is increased
      levels of vascular endothelial growth factor (VEGF). For the investigation of
      sevoflurane's effect on angiogenesis, the angiogenesis and VEGF expression in the
      retina were measured after administering sevoflurane in an oxygen-induced
      retinopathy mice model. MATERIALS AND METHODS: The mice were divided into the
      normoxic group (Nc and Ns group; n = 6) and the ROP group (C, Rc, and Rs group; n
      = 6). Rc group were exposed to 75% oxygen for 5 days beginning on postnatal day
      (P) 7, and then returned to room air. Age-matched mice in the C group were
      exposed to room air. To observe angiogenesis of the retina, the mice were
      sacrificed on P16. The Rs group was exposed to 2 vol% sevoflurane for 2 h on P12,
      P13, and P14 with 40% oxygen. RESULTS: The angiogenic area and the spreading
      distance of vessels on P4 were statistically decreased in the Ns group, compared
      to the Nc group. The avascular area on P16 was significantly increased and the
      expression of VEGF was suppressed in the Rs group compared to the Rc group.
      CONCLUSIONS: Sevoflurane can inhibit retinal angiogenesis via suppressing VEGF
      expression in an OIR mice model with exposure to relative hypoxia. Nevertheless,
      it is still difficult to apply the results of this study immediately to humans
      because of the heterogeneity of responses to sevoflurane.

PMID- 29464333
TI  - Catalysis of the acetylene hydrochlorination reaction by Si-doped Au clusters: a
      DFT study.
AB  - The mechanisms for the acetylene hydrochlorination reaction on pristine Au7 and
      Au8 clusters and on the Si-doped Au clusters Au6Si and Au7Si were systematically
      investigated via density functional theory using the PBE functional. The band gap
      (?Eg) of the Au7Si cluster was found to smaller than that of its undoped
      equivalent (Au8), thus enhancing its catalytic activity, and Au7Si presented a
      significantly reduced activation barrier (16.69 kcal mol-1) for the acetylene
      hydrochlorination reaction compared with the pristine Au8 cluster (21.83 kcal mol
      1). On the other hand, the activation barrier for the acetylene hydrochlorination
      reaction was not lower for the Au6Si cluster than for the pristine Au7 cluster
      because the band gap (?Eg) of Au6Si was found to be larger than that of Au7.
      Hence, the current work shows that the catalytic activities of gold clusters can
      be systematically modified by doping them. Our findings also suggest how to
      enhance the acetylene hydrochlorination reaction by doping foreign atoms into Au
      clusters. Graphical abstract The Si-doped Au7Si cluster showed stronger catalytic
      activity for the acetylene hydrochlorination reaction compared with the pristine
      Au8 cluster.

PMID- 29464334
TI  - Investigating the influence of electrode Miller indices alteration on electronic
      transport in thiophene-based molecular junctions.
AB  - Electrical charge transport through thiophene-dithiol-based molecular wires
      attached to gold electrodes with three different types of crystallographic
      orientations (<1,1,1>, <1,1,0 > and <1,0,1 >) was investigated. Electron
      transport in the systems under consideration was evaluated systematically by
      analyzing current values, transmission spectrum, projected device density of
      states and zero bias orbital analysis utilizing density functional theory in
      conjunction with non-equilibrium Green's function. Investigations proved that
      tuning of conductance in nano-molecular junctions is possible through different
      electrode orientations. As the HOMO-LUMO gap in the <1,1,0 > oriented thiophene
      dithiol junction is drastically less than that of the other configurations under
      consideration, the <1,1,0 > configuration exhibited superior constructive
      conductance in comparison to other junction orientations. This provided us with
      ideas for designing pioneering hetero-cyclic nano-scale electronics devices.
      Also, <1,1,0 > has been found to show negative differential conductance behavior
      above +2.6 V and below -2.6 V, and hence has potential applications in
      oscillating and switching circuits.

PMID- 29464335
TI  - Theoretical study of the NMR chemical shift of Xe in supercritical condition.
AB  - In this work we investigate the level of theory necessary for reproducing the non
      linear variation of the 129Xe nuclear magnetic resonance (NMR) chemical shift
      with the density of Xe in supercritical conditions. In detail we study how the
      129Xe chemical shift depends under supercritical conditions on electron
      correlation, relativistic and many-body effects. The latter are included using a
      sequential-QM/MM methodology, in which a classical MD simulation is performed
      first and the chemical shift is then obtained as an average of quantum
      calculations of 250 MD snapshots conformations carried out for Xe n clusters (n =
      2 - 8 depending on the density). The analysis of the relativistic effects is made
      at the level of 4-component Hartree-Fock calculations (4c-HF) and electron
      correlation effects are considered using second order Moller-Plesset perturbation
      theory (MP2). To simplify the calculations of the relativistic and electron
      correlation effects we adopted an additive scheme, where the calculations on the
      Xe n clusters are carried out at the non-relativistic Hartree-Fock (HF) level,
      while electron correlation and relativistic corrections are added for all the
      pairs of Xe atoms in the clusters. Using this approach we obtain very good
      agreement with the experimental data, showing that the chemical shift of 129Xe in
      supercritical conditions is very well described by cluster calculations at the HF
      level, with small contributions from relativistic and electron correlation
      effects.

PMID- 29464336
TI  - Current concepts in joint pain in knee osteoarthritis.
AB  - Joint pain attributable to osteoarthritis (OA) is complex and influenced by a
      myriad of factors beyond local joint pathology. Current practice continues to
      predominantly adopt a biomedical approach to OA despite emerging evidence of the
      importance of a more holistic approach. This paper will summarise evidence for
      the presence of multidimensional pain profiles in knee joint pain and the
      presence of subgroups characterized by systemic features such as psychological
      distress, high comorbidity load or sensitisation of the nervous system. These
      factors have the potential to influence patient outcomes making them relevant for
      clinicians and highlighting the necessity of a broader multifactorial approach to
      assessment and treatment. This review describes the current state of the evidence
      for treatments of people with knee OA-related pain, including those receiving
      strong recommendations from current clinical guidelines, namely exercise, weight
      loss, self-management advice and pharmacological approaches. Other pain
      modulating treatment options are emerging such as sleep and psychological
      interventions, pain education and multisensory retraining. The evidence and
      rationale for these newer therapeutic approaches is discussed. Finally, this
      review will highlight some of the limitations of current international guidelines
      for the management of OA and make recommendations for future research.

PMID- 29464337
TI  - Health risk assessment on human exposed to heavy metals in the ambient air PM10
      in Ahvaz, southwest Iran.
AB  - Heavy metals (HM) are one of the main components of urban air pollution. Today,
      megacities and industrial regions in southwest of Iran are frequently suffering
      from severe haze episodes, which essentially caused by PM10-bound heavy metals.
      The purpose of this study was to evaluate the health risk assessment on human
      exposed to heavy metals (Cr, Ni, Pb, and Zn) in the ambient air PM10 in Ahvaz,
      southwest Iran. In this study, we estimated healthy people from the following
      scenarios: (S3) residential site; (S2) high-traffic site; (S1) industrial site in
      Ahvaz metropolitan during autumn and winter. In the current study, high-volume
      air samplers equipped with quartz fiber filters were used to sampling and
      measurements of heavy metal concentration. Inductively coupled plasma optical
      emission spectroscopy (ICP-OES) was utilized for detection of heavy metal
      concentration (ng m-3). Also, an estimate of the amount of health risk assessment
      (hazard index) of Cr, Ni, Pb, and Zn of heavy metal exposure to participants was
      used. Result of this study showed that the residential and industrial areas had
      the lowest and the highest level of heavy metal. Based on the result of this
      study, average levels of heavy metal in industrial, high-traffic, and residential
      areas in autumn and winter were 31.48, 30.89, and 23.21 MUg m-3 and 42.60, 37.70,
      and 40.07 MUg m-3, respectively. Based on the result of this study, the highest
      and the lowest concentration of heavy metal had in the industrial and residential
      areas. Zn and Pb were the most abundant elements among the studied PM10-bound
      heavy metals, followed by Cr and Ni. The carcinogenic risks of Cr, Pb, and the
      integral HQ of metals in PM10 for children and adults via inhalation and dermal
      exposures exceeded 1 * 10-4 in three areas. Also, based on the result of this
      study, the values of hazard index (HI) of HM exposure in different areas were
      significantly higher than standard. The health risks attributed to HM should be
      further investigated from the perspective of the public health in metropolitans.
      The result of this study showed increasing exposure concentrations to heavy metal
      in the studied scenarios have a significant potential for generating different
      health endpoints, while environmental health management in ambient air can cause
      disorders in citizenship and causing more spiritual and material costs.

PMID- 29464338
TI  - Correction to: 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 original article mistakenly displays each set of author names in the wrong
      order, i.e., first names as last names and vice versa. The author correct names
      are: Tamas Gati, Ildiko Katalin Tefner, Lajos Kovacs, Katalin Hodosi, Tamas
      Bender. The original article has been corrected.

PMID- 29464339
TI  - New GJA8 variants and phenotypes highlight its critical role in a broad spectrum
      of eye anomalies.
AB  - GJA8 encodes connexin 50 (Cx50), a transmembrane protein involved in the
      formation of lens gap junctions. GJA8 mutations have been linked to early onset
      cataracts in humans and animal models. In mice, missense mutations and homozygous
      Gja8 deletions lead to smaller lenses and microphthalmia in addition to cataract,
      suggesting that Gja8 may play a role in both lens development and ocular growth.
      Following screening of GJA8 in a cohort of 426 individuals with severe congenital
      eye anomalies, primarily anophthalmia, microphthalmia and coloboma, we identified
      four known [p.(Thr39Arg), p.(Trp45Leu), p.(Asp51Asn), and p.(Gly94Arg)] and two
      novel [p.(Phe70Leu) and p.(Val97Gly)] likely pathogenic variants in seven
      families. Five of these co-segregated with cataracts and microphthalmia, whereas
      the variant p.(Gly94Arg) was identified in an individual with congenital aphakia,
      sclerocornea, microphthalmia and coloboma. Four missense variants of unknown or
      unlikely clinical significance were also identified. Furthermore, the screening
      of GJA8 structural variants in a subgroup of 188 individuals identified
      heterozygous 1q21 microdeletions in five families with coloboma and other ocular
      and/or extraocular findings. However, the exact genotype-phenotype correlation of
      these structural variants remains to be established. Our data expand the spectrum
      of GJA8 variants and associated phenotypes, confirming the importance of this
      gene in early eye development.

PMID- 29464340
TI  - Correction to: High-intensity aerobic interval training can lead to improvement
      in skeletal muscle power among in-hospital patients with advanced heart failure.
AB  - In the original publication of the article, the unit of hand in Fig. 2 was
      wrongly given as "N/kg" instead of "kg".

PMID- 29464341
TI  - Additional cryoapplications at the pulmonary vein antrum using a 28-mm second
      generation cryoballoon: a pilot study of extra-pulmonary vein ablation.
AB  - Isolation areas post-28-mm cryoballoon pulmonary vein isolation (CB-PVI) are
      smaller than post-radiofrequency PV antrum isolation at the left superior PV
      (LSPV) antrum and recurrent atrial fibrillation (AF) can originate from this
      area. This pilot study evaluated the impact of additional extra-PV CB
      applications at the LSPV antrum following conventional CB-PVI. Eighteen
      paroxysmal AF patients underwent CB-PVI with single 3-min freeze techniques.
      Following the CB-PVI, 2-min CB applications were added once or twice at the LSPV
      antrum. Before and after extra-PV ablation, left atrial (LA) 3-D
      electroanatomical maps were created. Seventy-two total PVs were successfully
      isolated with 4.2 +/- 0.4 applications/patient with 28-mm CBs. The mean LA
      posterior wall (LAPW) and non-isolated LAPW areas were 14.9 +/- 3.6 and 6.9 +/-
      2.8 cm2, respectively. After 1.6 +/- 0.5 mean extra-PV applications, the upper
      non-isolated LAPW area significantly decreased from 3.3 +/- 1.8 to 2.5 +/- 1.8
      cm2 (p < 0.001). The lowest esophageal temperatures during the extra-PV ablation
      were 27  degrees C. The total procedure and fluoroscopic times were 72.8 +/- 13.1
      and 15.2 +/- 5.9 min, respectively. Silent gastric hypomotility was detected in
      2/9 patients 1 day later, and mild PV stenosis was observed in 4/72 PVs 3 months
      later, but did not progress. At 12-month after single procedures, 16 (88.9%)
      patients were free from recurrent AF off antiarrhythmic drugs. A median of 8.0
      [6.0-10.0] months later, PV reconnections were detected in 3/12 (25.0%) PVs. The
      non-isolated LAPW area was significantly larger in the chronic than acute phase
      (14.3 +/- 5.2 cm2, p = 0.016). This pilot study suggested the potential
      feasibility of additional LSPV antral cryoapplications following a conventional
      CB-PVI. The strategy warrants further study in more patients.

PMID- 29464342
TI  - Vascular response to biolimus A-9 eluting stent in patients with shorter and
      prolonged dual antiplatelet therapy: optical coherence tomography sub-study of
      the NIPPON trial.
AB  - Dual antiplatelet therapy (DAPT) with thienopyridine and aspirin is the standard
      care for the prevention of stent thrombosis. However, the optimal duration and
      effect of the duration of DAPT on intra-stent thrombus (IS-Th) formation are
      unknown. The NIPPON study (Nobori Dual Antiplatelet Therapy as Appropriate
      Duration) was an open label, randomized multicenter, assessor-blinded, trial
      designed to demonstrate the non-inferiority of shorter (6-month) DAPT to
      prolonged (18-month) DAPT, after biolimus A9 eluting stent implantation in 3773
      patients at 130 sites in Japan. Among them, 101 patients were randomly allocated
      for an optical coherence tomography (OCT) sub-study to assess the difference of
      local IS-Th formation between the two groups. In addition to standard OCT
      parameters, the number of IS-Th formed was counted in each target stent at 8
      months. Baseline patient characteristics were not different between the 6- and 18
      month groups. IS-Th was detected in 9.8% of the cases and the presence of IS-Th
      was not significantly different between the two groups (10.9% in 6-month vs. 9.1%
      in 12-month, P = 0.76). Furthermore, the number of IS-Th formed was not
      significantly different between the two groups. This OCT sub-study was in line
      with the main NIPPON study which demonstrated the non-inferiority of 6-month DAPT
      to 18-month DAPT. Shorter DAPT duration did not promote progressive IS-Th
      formation at the mid-term time point.

PMID- 29464343
TI  - Prognostic Significance of Platelet-Based Inflammatory Indicators in Patients
      with Gastric Cancer.
AB  - BACKGROUND: Thrombocytosis develops in association with malignant tumors and may
      reflect the inflammation status in cancer patients. This study retrospectively
      investigated the prognostic significance of two platelet-based inflammatory
      indicators, the platelet * C-reactive protein multiplier value (P-CRP), and
      platelet-lymphocyte ratio (PLR), in gastric cancer patients. METHODS: The 453
      enrolled patients had a histopathological diagnosis of gastric adenocarcinoma and
      underwent curative surgery. RESULTS: P-CRP correlated significantly with age,
      tumor size, depth of invasion, lymph node metastasis, and disease stage. A high
      PLR correlated significantly with tumor size, depth of invasion, lymph node
      metastasis, lymphatic involvement, venous involvement, and disease stage. In the
      ROC analysis, the optimal cutoff value of P-CRP and PLR was 3.689 and 173.3,
      respectively. Five-year survival rates were 62.9 and 82.1% in patients with P
      CRPHigh (>=3.689) and P-CRPLow (<3.698), respectively (P < 0.0001). Five-year
      survival rates were 66.3 and 81.3% in patients with PLRHigh (>=173.3) and PLRLow
      (<173.3), respectively (P = 0.0022). The prognosis of the P-CRPHigh/PLRHigh group
      was significantly worse than that of the P-CRPHigh or PLRHigh and P-CRPLow/PLRLow
      groups in terms of overall survival (P < 0.0001) and disease-specific survival (P
      = 0.029). In a multivariate analysis, the combination of P-CRP and PLR was an
      independent prognostic indicator. CONCLUSIONS: The combination of P-CRP and PLR
      may be useful in predicting prognosis in gastric cancer patients.

PMID- 29464344
TI  - A Novel Classification and Staged Approach for Dissection Along the Celiac and
      Hepatic Artery During Pancreaticoduodenectomy.
AB  - BACKGROUND: In recent decades, there have been enthusiastic discussions of, and
      active proposals for, new approaches to dissection around the superior mesenteric
      artery during pancreaticoduodenectomy (PD). In contrast, dissection along the
      celiac axis (CA) and hepatic artery (HA) and in the hepatoduodenal ligament has
      rarely been systematically discussed. In this report, we propose and describe a
      three-level classification of dissection along the CA-HA system which is
      applicable to a variety of diseases for which PD is indicated. METHODS: The
      extent of dissection is classified into three levels. With the first level (LV
      1), neither LN nor plexus dissection is required. The second level (LV-2)
      includes en bloc resection of LNs along the CA, HA, and in the hepatoduodenal
      ligament, preserving the nerve plexus around the artery. The third level (LV-3)
      includes en bloc dissection of LNs and the nerve plexus close to cancer invasion,
      for example, being accompanied by half circumferential dissection of the nerve
      plexus around the CA or circumferential dissection of that of HA. LV-1 dissection
      is indicated for benign lesions, low grade malignancy, pancreatic metastasis, or
      intraductal papillary mucinous neoplasm. LV-2 is indicated for periampullary
      malignancies requiring dissection of regional LNs, including ampullary, distal
      bile duct, duodenal cancers, and pancreatic cancers without evidence of invasion
      around the CA-HA system. LV-3 is indicated for malignancies with evidence of
      perineural invasion in the CA-HA system, such as pancreatic cancer at the
      pancreatic neck or advanced bile duct cancer. CONCLUSIONS: In combination with
      classified superior mesenteric artery dissection, a variety of PD procedures
      would be systematically classified, understood, and reproduced regardless of
      nature of disease, surgeon, or approach.

PMID- 29464345
TI  - Prognostic Impact of Bacterobilia on Morbidity and Postoperative Management After
      Pancreatoduodenectomy: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Intraoperative bile analysis during pancreatoduodenectomy (PD) is
      performed routinely at specialized centers worldwide. However, it remains
      controversial if and how intraoperative bacterobilia during PD affects morbidity
      and its management. The aim of the study was a systematic review and meta
      analysis of intraoperative bacterobilia and its impact on patient outcome after
      PD. METHODS: Five relevant outcomes of interest were defined, and a systematic
      review of the literature with meta-analysis was performed according to the PRISMA
      guidelines. RESULTS: A total of 28 studies (8523 patients) were included. The
      median incidence of bacterobilia was 58% (interquartile range 51-67%). The most
      frequently isolated bacteria were Enterococcus species (51%), Klebsiella species
      (28%), and Escherichia coli (27%). Preoperative biliary drainage was
      significantly associated with bacterobilia (86 vs. 25%; RR 3.27; 95% confidence
      interval (CI) 2.42-4.42; p < 0.001). The incidence of surgical site infections
      (SSI) was significantly increased in cases with bacterobilia (RR 2.84; 95% CI
      2.17-3.73; p < 0.001). Postoperative pancreatic fistula, overall postoperative
      morbidity, and mortality were not significantly influenced. Identical bacteria in
      bile and the infectious sources were found in 48% (interquartile range 34-59%) of
      the cases. CONCLUSIONS: Bacterobilia is detected during almost every second PD
      and is associated with an increased rate of SSI. The microbiome from
      intraoperative bile and postoperative infectious sources match in ~50% of
      patients, providing the option of early administration of calculated antibiotics
      and the determination of resistance patterns.

PMID- 29464347
TI  - Dietary carbohydrate rather than protein intake drives colonic microbial
      fermentation during weight loss.
AB  - PURPOSE: High protein weight loss diets are effective in aiding body weight
      management. However, high protein and low carbohydrate intakes can alter colonic
      fermentation profiles in humans and may impact on colonic health. This study aims
      to identify the most important dietary contributors to colonic fermentation
      during diet-controlled weight loss. METHODS: Overweight or obese male volunteers
      (n = 18) consumed a body weight maintenance diet (fed at 1.5* basic metabolic
      rate, BMR) followed by three weight loss diets (fed at 1* BMR) for 10 days each
      in a cross-over design. Weight loss diets were designed as normal protein (NPWL,
      15% of energy from protein, 55% from carbohydrate), normal protein enriched with
      free amino acids and moderate amounts of carbohydrate (NPAAWL, 15% of energy from
      protein, 15% from free AA, 40% from carbohydrate) or high protein containing
      moderate amounts of carbohydrate (HPWL, 30% of energy from protein, 40% from
      carbohydrate). Faecal samples collected at the end of each diet period were
      profiled for dietary metabolites using LC-MS/MS. RESULTS: This study shows that
      the NPWL diet only induced very minor changes in the faecal metabolome, whereas
      NPAAWL and HPWL diets decreased carbohydrate-related metabolites (butyrate,
      ferulic acid) and increased protein-related metabolites. Most faecal metabolites
      were correlated with dietary carbohydrate and not protein intake. CONCLUSION:
      This study demonstrates that dietary carbohydrate is the main driver of colonic
      fermentation in humans and that a balance between dietary carbohydrate and
      protein should be maintained when designing safe, effective and healthy weight
      loss diets.

PMID- 29464346
TI  - Systematic Review and Meta-analysis of Restrictive Perioperative Fluid Management
      in Pancreaticoduodenectomy.
AB  - BACKGROUND: There is significant interest and controversy surrounding the effect
      of restrictive fluid management on outcomes in major gastrointestinal surgery.
      This has been most studied in colorectal surgery, although the literature
      relating to pancreaticoduodenectomy (PD) patients is growing. The aim of this
      paper was to generate a comprehensive review of the available evidence for
      restrictive perioperative fluid management strategies and outcomes in PD.
      METHODS: MEDLINE/PubMed, Embase, and the Cochrane Library were searched from
      inception to April 2017. A review protocol was utilized and registered with
      PROSPERO. Primary citations that evaluated perioperative fluid management in PD,
      including those as part of a clinical pathway, were considered. The primary
      outcome was postoperative pancreatic fistula (POPF). Secondary outcomes included
      delayed gastric emptying (DGE), complication rate, length of stay (LOS),
      mortality, and readmission. RESULTS: A total of six studies involving 846
      patients were included (2009-2015), of which four were RCTs. Pooled analysis of
      RCTs and high-quality observational studies found no effect of restrictive
      intraoperative fluid management on POPF, DGE, complication rate, LOS, mortality,
      and readmission. Only one study assessed postoperative fluid management
      exclusively and found prolonged LOS in patients in the restricted fluid group.
      CONCLUSION: Based on results of RCTs and high-quality observational studies,
      intraoperative fluid restriction in PD has not been shown to significantly affect
      postoperative outcomes. There are too few studies assessing postoperative fluid
      management to draw conclusions at this time.

PMID- 29464348
TI  - Correction to: Effects of supplementation with rice husk powder and rice bran on
      inflammatory factors in overweight and obese adults following an energy
      restricted diet: a randomized controlled trial.
AB  - In the original publication, one of the author's name was misspelled. The correct
      name is "Salma Mahmoodianfard". The original article was corrected.

PMID- 29464349
TI  - Treatment and outcome of patients with localized intrathoracic and chest wall
      rhabdomyosarcoma: a report of the Cooperative Weichteilsarkom Studiengruppe
      (CWS).
AB  - PURPOSE: Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma.
      In 7% of the cases it is localized at the chest wall or intrathoracically. The
      aim of this study was to analyze the multimodal treatment concepts and outcomes
      of children suffering from intrathoracic and chest wall RMS treated within three
      different Cooperative Soft Tissue Sarcoma (CWS) trials and one registry (Soft
      Tissue Sarcoma Registry, SoTiSaR). METHODS: Data of 51 patients with thoracic RMS
      enrolled in three different CWS trials (CWS-86, -91, -2002P) and one registry
      (SoTiSaR) were analyzed retrospectively. Surgery and its influence on outcome
      were assessed. Median follow-up was 37.5 months (0.9-152.5). RESULTS: Median age
      of the patients was 8.8 years (range 0-19 years). The 5-year overall survival
      rate (OS) was 57% (95%-CI 49-65) and the 5-year event-free survival rate (EFS)
      was 45% (38-52). Thirty-five patients had tumors located at the chest wall (EFS:
      51%, 43-59), and 16 patients had intrathoracic tumors (EFS: 26%, 13-39).
      Seventeen patients with tumors <= 5 cm had a better outcome (EFS: 64%, 52-76)
      compared to patients with tumors larger than 5 cm (EFS: 36%, 27-45). Radiotherapy
      (RT) significantly improved the survival of patients with alveolar RMS compared
      to patients with embryonal histology (EFS: 66%, 52-80 vs. 32%, 21-43 p = 0.02).
      Complete tumor excision during delayed surgery was the main prognostic factor for
      survival (p = 0.045). CONCLUSION: Thoracic RMS is a rare tumor entity.
      Completeness of tumor resection significantly improved survival of the patients.

PMID- 29464350
TI  - NIPA-like domain containing 1 is a novel tumor-promoting factor in oral squamous
      cell carcinoma.
AB  - PURPOSE: In our previous global gene expression analysis, we identified NIPA-like
      domain containing 1 (NIPAL1), which encodes a magnesium transporter, as one of
      the most overexpressed genes in recurrent oral squamous cell carcinoma (OSCC).
      Although has been NIPAL1 linked with gout pathogenesis, little is known about its
      expression and function in human malignancies. METHODS: In this study, we
      examined NIPAL1 expression in 192 cases of OSCC by immunohistochemistry and
      performed a functional analysis of human OSCC cells. RESULTS: NIPAL1
      immunostaining was observed in 39 of 192 OSCC patients (20.3%). NIPAL1 expression
      correlated significantly with cancer cell intravsation (P = 0.0062), as well as
      with poorer disease-free survival in a Kaplan-Meier analysis (P < 0.0001).
      Moreover, a multivariate Cox proportional hazards model analysis revealed that
      NIPAL1 expression was an independent predictor of disease-free survival in OSCC
      (P < 0.0001). In a functional analysis, NIPAL1 regulated the growth and adhesion
      of OSCC tumor cells and endothelial cells. CONCLUSIONS: Our findings suggest that
      NIPAL1 might be a novel factor promoting OSCC tumorigenesis, as well as a useful
      molecular marker of OSCC.

PMID- 29464351
TI  - Vasculitis in Africa.
AB  - PURPOSE OF REVIEW: Systemic vasculitides are characterized by inflammation of
      blood vessel walls leading to a myriad of organ disorders depending on the size,
      site, and location of the affected blood vessel. The epidemiology of vasculitis
      in the developing world has been inadequately documented. The description of the
      vasculitides in Africa, both from hospital series as well as taking into
      consideration, previous epidemiological studies in the community, indicates that
      these conditions have been rare until relatively recently. In view of these past
      observations, this review of publications on the topic looks to shed light on the
      current state of vasculitis in Africa. RECENT FINDINGS: Takayasu and Kawasaki
      appear to be the most commonly reported vasculitides in Africa. Most of the
      published reports are from North and South Africa. Furthermore, the contribution
      of vasculitis associated with infections, and in particular HIV, is significant.
      There are increasing numbers of publications reflecting a growing recognition of
      the vasculitides in Africa.

PMID- 29464352
TI  - Preparation of TPP-crosslinked chitosan microparticles by spray drying for the
      controlled delivery of progesterone intended for estrus synchronization in
      cattle.
AB  - PURPOSE: Planned reproduction in cattle involves regulation of estrous cycle and
      the use of artificial insemination. Cycle control includes the administration of
      exogenous progesterone during 5-8 days in a controlled manner allowing females to
      synchronize their ovulation. Several progesterone delivery systems are
      commercially available but they have several drawbacks. The aim of the present
      contribution was to evaluate chitosan microparticles entrapping progesterone as
      an alternative system. METHODS: Microparticles were prepared by spray drying. The
      effect of formulation parameters and experimental conditions on particle features
      and delivery was studied. A mathematical model to predict progesterone plasma
      concentration in animals was developed and validated with experimental data.
      RESULTS: Microparticle size was not affected by formulation parameters but
      sphericity enhances as Tween 80 content increases and it impairs as TPP content
      rises. Z potential decreases as phosphate content rises. Particles remain stable
      in acidic solution but the addition of surfactant is required to stabilize
      dispersions in neutral medium. Encapsulation efficiencies was 69-75%. In vitro
      delivery studies showed burst and diffusion-controlled phases, being progesterone
      released faster at low pH. In addition, delivery extend in cows was affected
      mainly by particle size and hormone initial content, while the amount injected
      altered plasma concentration. Theoretical predictions with excellent accuracy
      were obtained. CONCLUSION: The mathematical model developed can help to find
      proper particle features to reach specific delivery rates in the animals. This
      not only save time, money and effort but also minimized experimentation with
      animals which is desired from an ethical point of view.

PMID- 29464353
TI  - Cardio-pulmonary responses to incremental eccentric and concentric cycling tests
      to task failure.
AB  - PURPOSE: This study compared cardio-pulmonary responses between incremental
      concentric and eccentric cycling tests, and examined factors affecting the
      maximal eccentric cycling capacity. METHODS: On separate days, nine men and two
      women (32.6 +/- 9.4 years) performed an upright seated concentric (CON) and an
      eccentric (ECC) cycling test, which started at 75 W and increased 25 W min-1
      until task failure. Gas exchange, heart rate (HR) and power output were
      continuously recorded during the tests. Participants also performed maximal
      voluntary contractions of the quadriceps (MVC), squat and countermovement jumps.
      RESULTS: Peak power output was 53% greater (P < 0.001, g = 1.77) for ECC (449 +/-
      115 W) than CON (294 +/- 61 W), but peak oxygen consumption was 43% lower (P <
      0.001, g = 2.18) for ECC (30.6 +/- 5.6 ml kg min-1) than CON (43.9 +/- 6.9 ml kg
      min-1). Maximal HR was not different between ECC (175 +/- 20 bpm) and CON (182 +/
      13 bpm), but the increase in HR relative to oxygen consumption was 33% greater
      (P = 0.01) during ECC than CON. Moderate to strong correlations (P < 0.05) were
      observed between ECC peak power output and CON peak power (r = 0.84), peak oxygen
      consumption (r = 0.54) and MVC (r = 0.53), while no significant relationships
      were observed between ECC peak power output and squat as well as countermovement
      jump heights. CONCLUSION: Unexpectedly, maximal HR was similar between CON and
      ECC. Although ECC power output can be predicted from CON peak power output, an
      incremental eccentric cycling test performed after 3-6 familiarisation sessions
      may be useful in programming ECC training with healthy and accustomed
      individuals.

PMID- 29464354
TI  - PARP inhibitors in platinum-sensitive high-grade serous ovarian cancer.
AB  - PURPOSE: Poly(ADP-ribose) polymerase inhibitors (PARPi) have changed the
      management of high-grade serous ovarian cancer (HGSOC). The rationale for the
      development of PARPi was based on the concept of synthetic lethality, in which a
      cell can survive a deficiency of one gene/gene product, but may die if there is a
      deficiency in a combination of genes/gene products. In women with BRCA1/2
      deficiency within their ovarian cancer tissue, inhibition of PARP imposes an
      intolerable burden of DNA damage repair deficiency and may induce cell death.
      METHODS: Clinical trials have evaluated PARPi as single-agent therapeutics and as
      maintenance treatment following platinum-based chemotherapy for HGSOC. Clinical
      data suggest the most impressive anti-tumour activity occurs in women with
      platinum-sensitive ovarian cancer and germline or somatic BRCA1/2 mutations
      (g/sBRCAmt). RESULTS: In the maintenance setting, randomised trials have shown
      that PARPi compared to placebo reduce the hazard ratio for the development of
      progressive disease to 0.2-0.27 for patients with a g/sBRCAmt; to 0.34-0.38 for
      patients with putative evidence of DNA damage repair deficiency; and to 0.35-0.45
      in an unselected population with HGSOC. Furthermore, phase 1/2 trials have
      reported single-agent anti-tumour response rates in gBRCAmt of approximately 50%
      in platinum-sensitive and 25% in platinum-resistant disease. CONCLUSION: Here, we
      discuss the evidence for the use of PARPi as single-agent therapeutics and
      maintenance treatment in HGSOC and evaluate the genetic assays used in clinical
      trials so far. We discuss the emerging role of platinum sensitivity as a broad
      eligibility criteria for the use of PARPi.

PMID- 29464355
TI  - FDG PET/CT after first molecular targeted therapy predicts survival of patients
      with renal cell carcinoma.
AB  - PURPOSE: We investigated prospectively whether 18F-2-fluoro-2-deoxyglucose
      positron emission tomography/computed tomography (FDG PET/CT) can predict the
      overall survival (OS) of patients with advanced renal cell carcinoma (RCC)
      previously treated by molecular targeted therapies. METHODS: Between 2009 and
      2016, 81 patients who had received single molecular targeted therapies (43
      sorafenib, 27 sunitinib, 8 temsirolimus and others) and were scheduled for second
      line molecular targeted therapies for advanced RCC were enrolled in this
      prospective study. FDG PET/CT was performed after first line molecular targeted
      therapies, the max SUVmax (highest standardized uptake value for each patient)
      recorded, and its association with OS compared with those of known risk factors.
      The median follow-up was 15.4 months (range 0.9-97.4 months). RESULTS: The max
      SUVmax of the 81 subjects ranged from undetectable to 23.0 (median 7.1). Patients
      with high max SUVmax had a poor prognosis and multivariate analysis with
      established risk factors showed that it was an independent predictor of survival
      (p < 0.001; hazard ratio 1.156; 95% confidence interval 1.080-1.239).
      Subclassification of patients by max SUVmax showed that the median OS of patients
      with max SUVmax < 7.0 (39), 7.0-12.0 (30), and >= 12.0 (12) were 32.8, 15.2, and
      6.0 months, respectively. These differences are statistically significant (< 7.0
      versus 7.0-12.0: p = 0.0333, 7.0-12.0 versus >= 12.0: p = 0.0235). CONCLUSIONS:
      The max SUVmax by FDG PET/CT of patients with RCC evaluated after their first
      molecular targeted therapy predicts OS. FDG PET/CT is a useful "imaging
      biomarker" for patients with advanced RCC planning sequential molecular targeted
      therapies.

PMID- 29464357
TI  - Decreased bone mineral density in women with Sheehan's syndrome and improvement
      following oestrogen replacement and nutritional supplementation.
AB  - Sheehan's syndrome (SS) is an important cause of pan-hypopituitarism in women.
      There is scanty information on bone mineral density (BMD) in this condition. We
      determined BMD and the changes in BMD after oestrogen (E2) replacement and
      nutritional supplementation in women with SS. In a cross-sectional study, BMD was
      measured by DEXA in 83 patients [age (mean +/- SD) 42 +/- 9.2 years] and compared
      with an equal number of matched controls. In a sub-set of 19 patients, we
      conducted an open-label, prospective study to determine changes in BMD after 1
      year of replacement of E2, and calcium and vitamin D3 supplementation. All
      patients had low serum IGF-1 and E2, while 98% had >= 3 pituitary hormone
      deficiencies. Compared with Indian reference standards, 47% had decreased bone
      mass (Z-score <= - 2.0). BMD Z-scores were decreased at all sites, being most
      marked in the lumbar spine and femoral neck. At the lumbar spine, BMD was lowest
      among the age group 21-30 years. Women with SS also had significantly lower BMD Z
      scores at all three sites on comparison with ethnic controls. On multivariate
      analysis, BMD Z-score was associated with weight, daily calcium intake and age
      (lumbar spine). In the prospective study, 1 year of therapy improved BMD Z-score
      at lumbar spine (- 1.4 +/- 1.2 vs. - 1.1 +/- 1.1, p = 0.02), but not at hip or
      femoral neck. In conclusion, patients with SS had significantly lower BMD
      compared to controls at all three sites. Replacement of E2 and supplementation
      with calcium/vitamin D3 lead to significant improvement in lumbar spine BMD.

PMID- 29464356
TI  - Weighing the Anti-Ischemic Benefits and Bleeding Risks from Aspirin Therapy: a
      Rational Approach.
AB  - PURPOSE OF REVIEW: The role of aspirin in secondary cardiovascular prevention is
      well understood; however, the role in primary prevention is less clear, and
      requires careful balancing of potential benefits with risks. Here, we summarize
      the evidence base on the benefits and risks of aspirin therapy, discuss clinical
      practice guidelines and decision support tools to assist in initiating aspirin
      therapy, and highlight ongoing trials that may clarify the role of aspirin in
      cardiovascular disease prevention. RECENT FINDINGS: In 2016, the USPSTF released
      guidelines on the use of aspirin for primary prevention. Based on 11 trials (n =
      118,445), aspirin significantly reduced all-cause mortality and nonfatal
      myocardial infarction, and in 7 trials that evaluated aspirin <= 100 mg/day,
      there was significant reduction in nonfatal stroke. The USPSTF recommends
      individualized use of aspirin based on factors including age, 10-year
      atherosclerotic cardiovascular disease risk score, and bleeding risk. Several
      ongoing trials are evaluating the role of aspirin in primary prevention,
      secondary prevention, and in combination therapy for atrial fibrillation.
      Evidence-based approaches to aspirin use should consider the anti-ischemic
      benefits and bleeding risks from aspirin. In this era of precision medicine,
      tools that provide the personalized benefit to risk assessment, such as the
      freely available clinical decision support tool (Aspirin-Guide), can be easily
      incorporated into the electronic health record and facilitate more informed
      decisions about initiating aspirin therapy for primary prevention. Aspirin has a
      complex matrix of benefits and risks, and its use in primary prevention requires
      individualized decision-making. Results from ongoing trials may guide healthcare
      providers in identifying appropriate candidates for aspirin therapy.

PMID- 29464358
TI  - Association of cystatin C- and creatinine-based eGFR with osteoporotic fracture
      in Japanese postmenopausal women with osteoporosis: sarcopenia as risk for
      fracture.
AB  - Coexistence of chronic kidney disease (CKD) is regarded as a risk for
      osteoporotic fracture particularly in postmenopausal women, not only because of
      increased parathyroid hormone level but also uremic sarcopenia. We examined the
      relationships of cystatin C-based glomerular filtration rate (eGFRcys) and
      creatinine-based GFR (eGFRcr), as well as their ratio with occurrence of
      osteoporotic fracture in postmenopausal osteoporotic women. This cross-sectional
      study included 555 postmenopausal women with osteoporosis. eGFRcr and eGFRcys
      were simultaneously measured, while occurrence of osteoporotic fracture was
      obtained by a medical chart review. Patients with osteoporotic fractures (n =
      211) exhibited significantly lower levels of physical activity, eGFRcr, eGFRcys,
      and eGFRcys/eGFRcr ratios, while a higher percentage was CKD stage 3 or more,
      estimated by eGFRcr or eGFRcys (CKDcys), than those without (n = 344). Lower
      eGFRcys, but not lower eGFRcr, was independently associated with osteoporotic
      fracture in the entire cohort and that association was retained in CKDcys
      patients. Of great interest, higher eGFRcr was associated with osteoporotic
      fracture independent of eGFRcys in CKDcys patients. Furthermore, lower
      eGFRcys/eGFRcr ratio was independently associated with osteoporotic fracture in
      both CKDcys patients and the entire cohort. eGFRcys reduction might be associated
      with osteoporotic fracture in postmenopausal osteoporotic women, indicating the
      involvement of renal osteopathy in its occurrence. Furthermore, the association
      of higher, but not lower, eGFRcr with osteoporotic fracture in CKDcys cases might
      be explained by underestimation of renal dysfunction by eGFRcr resulting from
      decreased muscle mass and quality in those patients.

PMID- 29464359
TI  - Dentinal tubule obliteration using toothpastes containing sodium trimetaphosphate
      microparticles or nanoparticles.
AB  - OBJECTIVES: This in vitro study evaluated the effect of microparticles (TMPmicro)
      or nanoparticles (TMPnano) TMP associated with fluoride (F) in toothpaste
      formulations on the obliteration of dentinal tubules (DT). MATERIALS AND METHODS:
      The dentinal tubules of bovine dentin blocks were unobstructed by immersion in
      37% phosphoric acid solution. Blocks (n = 20/group) underwent mechanical brushing
      (2*/day) during 7 days with toothpastes: placebo, 1100 ppm F, and 1100 with 3%
      TMPmicro or 3% TMPnano. After that, ten blocks of each group were immersed in
      citric acid (pH 3.2) for 1 min. The number, diameter and area of unobstructed DT,
      atomic % of chemical elements from precipitates, and the mineral concentration
      were quantified. Data were submitted to two-way ANOVA, followed by Student-Newman
      Keuls test (P < 0.05). RESULTS: Toothpastes containing TMPmicro and TMPnano
      promoted greater obliteration of DT and greater mineral concentration compared to
      other groups (P < 0.05). Placebo and 1100 ppm F group presented similar
      obliteration but 1100 ppm F group promoted higher mineral concentration. Higher
      Ca/P ratios were observed in groups treated with TMP; the acid challenge reduced
      Ca/P ratio for all groups. The atomic % of C and N was significantly lower for
      TMP toothpastes before acid challenge, but increased afterwards. CONCLUSIONS: It
      was concluded that the addition of TMPmicro or TMPnano to F toothpastes produced
      greater obliteration of dentinal tubules and higher mineral concentration when
      compared with 1100 ppm F. CLINICAL RELEVANCE: By the addition of TMP, fluoride
      toothpastes may occlude the dentinal tubules, with potential to reduce dentin
      hypersensitivity.

PMID- 29464361
TI  - Flavobacterium chungangensis sp. nov., a Bacterium Isolated from Soil of Chinese
      Cabbage Garden.
AB  - A novel bacterial strain MAH-10T was isolated from soil sample of a Chinese
      cabbage garden, Republic of Korea and was characterized using a polyphasic
      approach. Cells were Gram-staining negative, rod-shaped, yellowish orange
      colored, and motile. The strain was aerobic, catalase and oxidase are positive,
      and optimum growth temperature and pH were 28  degrees C and 6.5, respectively.
      Flexirubin-type pigments were found to be present. On the basis of 16S rRNA gene
      sequence analysis, strain MAH-10T belongs to the genus Flavobacterium and is most
      closely related to Flavobacterium tyrosinilyticum KCTC 42726T (98.7%). On the
      basis of phylogenetic tree, other closely related species are Flavobacterium
      banpakuense KACC 14225T (98.3%) and Flavobacterium chungbukense KACC 15048T
      (97.6%). In DNA-DNA hybridization tests, the DNA relatedness between strain MAH
      10T and its closest phylogenetic neighbor was below 45.0%. The DNA G+C content
      was 37.2 mol% and the predominant respiratory quinone was menaquinone-6. The
      major cellular fatty acids were C15:0 iso, C16:0, and summed feature 3
      (C16:1omega7c and/or C16:1omega6c). On the basis of DNA-DNA hybridization results
      and genotypic, chemotaxonomic, and physiological data analysis, it is
      demonstrated that strain MAH-10T represented a novel species within the genus
      Flavobacterium, for which the name Flavobacterium chungangensis is proposed. The
      type strain is MAH-10T (=KACC 19296T=CGMCC 1.16226T). The NCBI GenBank accession
      number for the 16S rRNA gene sequence of strain MAH-10T is KY964277 and the
      digital protologue database (DPD) Taxon Number of strain MAH-10T is TA00296.

PMID- 29464360
TI  - Identification and Analysis of a Novel Gene Cluster Involves in Fe2+ Oxidation in
      Acidithiobacillus ferrooxidans ATCC 23270, a Typical Biomining Acidophile.
AB  - Iron-oxidizing Acidithiobacillus spp. are applied worldwide in biomining industry
      to extract metals from sulfide minerals. They derive energy for survival through
      Fe2+ oxidation and generate Fe3+ for the dissolution of sulfide minerals.
      However, molecular mechanisms of their iron oxidation still remain elusive. A
      novel two-cytochrome-encoding gene cluster (named tce gene cluster) encoding a
      high-molecular-weight cytochrome c (AFE_1428) and a c4-type cytochrome c552
      (AFE_1429) in A. ferrooxidans ATCC 23270 was first identified in this study.
      Bioinformatic analysis together with transcriptional study showed that AFE_1428
      and AFE_1429 were the corresponding paralog of Cyc2 (AFE_3153) and Cyc1
      (AFE_3152) which were encoded by the extensively studied rus operon and had been
      proven involving in ferrous iron oxidation. Both AFE_1428 and AFE_1429 contained
      signal peptide and the classic heme-binding motif(s) as their corresponding
      paralog. The modeled structure of AFE_1429 showed high resemblance to Cyc1.
      AFE_1428 and AFE_1429 were preferentially transcribed as their corresponding
      paralogs in the presence of ferrous iron as sole energy source as compared with
      sulfur. The tce gene cluster is highly conserved in the genomes of four
      phylogenetic-related A. ferrooxidans strains that were originally isolated from
      different sites separated with huge geographical distance, which further implies
      the importance of this gene cluster. Collectively, AFE_1428 and AFE_1429 involve
      in Fe2+ oxidation like their corresponding paralog by integrating with the
      metalloproteins encoded by rus operon. This study provides novel insights into
      the Fe2+ oxidation mechanism in Fe2+-oxidizing A. ferrooxidans ssp.

PMID- 29464362
TI  - Inhibitory Mechanism on Combination of Phytic Acid with Methanolic Seed Extract
      of Syzygium cumini and Sodium Chloride over Bacillus subtilis.
AB  - The antibiotic resistance in bacteria responsible for causing community and
      health care-associated infection displayed a major threat to global health. Use
      of broad-spectrum antibiotics for the treatment of various ailments poses serious
      side effects. In the present research, we investigated the combined role of 2%
      phytic acid with 2% methanolic seed extract of Syzygium cumini and 0.5% sodium
      chloride for inhibition of Bacillus subtilis and Pseudomonas aeruginosa and found
      it to be efficient over B. subtilis. The zone of inhibition by present mixture
      was found to be 2.9 +/- 0.0004 and 1.9 +/- 0.0006 cm against Bacillus subtilis
      and P. aeruginosa in comparison to individual component. Mixture was found more
      potent against B. subtilis and selected for further study. The underlying
      mechanism involved in inhibitory action of this mixture was determined by
      Scanning electron microscope, DNA fragmentation and propidium iodide staining.
      Scanning electron microscopy revealed that inhibition of B. subtilis by this
      mixture is mainly due to the disruption of bacterial cell membrane, leakage of
      internal cellular content which ultimately leads to the death of bacterial cells.
      DNA fragmentation showed apoptotic hallmark through degradation caused by mixture
      against B. subtilis at various time intervals. Likewise, PI staining also
      revealed the disruption of bacterial membrane by the mixture as the PI gives
      fluorescence after binding with DNA. The present study concludes that inhibitory
      potential of this mixture is mainly due to disruption of bacterial cell membrane,
      degradation of DNA and creation of pores in the membrane. The mixture could be
      used for inhibition of food pathogen B. subtilis.

PMID- 29464364
TI  - Fatty acids promote bovine skeletal muscle satellite cell differentiation by
      regulating ELOVL3 expression.
AB  - Fatty acids (FAs) play essential roles in regulating differentiation and
      proliferation by affecting gene expression in various cell types. However, their
      potential functions in bovine cells remain unclear. Herein, we examine the
      differentiation and proliferation of bovine skeletal muscle-derived satellite
      cells (MDSCs) after incubation with three types of representative FAs (palmitic
      acid, oleic acid and docosahexaenoic acid) by western blotting,
      immunofluorescence assays, flow cytometry analysis and EdU incorporation assays.
      The myotube fusion rate, myotube length and expression levels of muscle
      differentiation-related gene myogenin (MYOG) and myosin heavy chain 3 (MYH3)
      increased significantly, although the FAs did not affect proliferation.
      Additionally, FA-induced bovine MDSC differentiation increased ELOVL3 expression
      and relocation of ELOVL3 to cytoplasmic lipid droplets in the differentiation of
      bovine MDSCs. Moreover, the effect of FAs on bovine MDSC differentiation was
      inhibited upon ELOVL3 downregulation. Collectively, these data indicate that FAs
      promote bovine MDSC differentiation by regulating ELOVL3 expression.

PMID- 29464363
TI  - Corallibacterium pacifica gen. nov., sp. nov., a Novel Bacterium of the Family
      Vibrionaceae Isolated from Hard Coral.
AB  - A gram-negative, rod-shaped, motile, oxidase- and catalase-positive, non
      pigmented marine bacterium, designated strain OS-11M-2T, was isolated from a
      coral sample collected from the Osakura coastal area in Micronesia. Phylogenetic
      analysis based on 16S ribosomal RNA (rRNA) gene sequences indicated that strain
      OS-11M-2T is a member of the family Vibrionaceae, its closest neighbors being
      Photobacterium damselae subsp. piscicida NCIMB 2058T (94.9%), Photobacterium
      damselae subsp. damselae CIP 102761T (94.75%), Grimontia marina IMCC5001T
      (94.5%), Enterovibrio coralii LMG 22228T (94.5%), and Grimontia celer 96-237T
      (94.5%). The major cellular fatty acids were summed feature 3 (21.4%), summed
      feature 8 (18.5%), iso-C16:0 (13.8%), and C16:0 (11.9%). The major respiratory
      quinone of the bacterium was ubiquinone-8 (Q-8) and its major polar lipid
      phosphatidylethanolamine. Six amino lipids, two phospholipids, and one polar
      lipid, all unidentified, were detected. The DNA G+C content was 49.7 mol%. The
      16S rRNA gene sequence of OS-11M-2T was registered in GenBank under accession
      number MF359550. On the basis of phenotypic, genotypic, and phylogenetic
      analyses, strain OS-11M-2T represents a novel genus of the family Vibrionaceae,
      for which we propose the name Corallibacterium pacifica gen. nov., sp. nov., with
      the type strain of the type species being OS-11M-2T (= KCCM 43265T). The digital
      protologue database (DPD) taxon number for strain OS-11M-2T is GA00041.

PMID- 29464365
TI  - Structural and functional maturation of skin during metamorphosis in the Atlantic
      halibut (Hippoglossus hippoglossus).
AB  - To establish if the developmental changes in the primary barrier and
      osmoregulatory capacity of Atlantic halibut skin are modified during
      metamorphosis, histological, histochemical, gene expression and
      electrophysiological measurements were made. The morphology of the ocular and
      abocular skin started to diverge during the metamorphic climax and ocular skin
      appeared thicker and more stratified. Neutral mucins were the main glycoproteins
      produced by the goblet cells in skin during metamorphosis. Moreover, the number
      of goblet cells producing neutral mucins increased during metamorphosis and
      asymmetry in their abundance was observed between ocular and abocular skin. The
      increase in goblet cell number and their asymmetric abundance in skin was
      concomitant with the period that thyroid hormones (THs) increase and suggests
      that they may be under the control of these hormones. Several mucin transcripts
      were identified in metamorphosing halibut transcriptomes and Muc18 and Muc5AC
      were characteristic of the body skin. Na+, K+-ATPase positive (NKA) cells were
      observed in skin of all metamorphic stages but their number significantly
      decreased with the onset of metamorphosis. No asymmetry was observed between
      ocular and abocular skin in NKA cells. The morphological changes observed were
      linked to modified skin barrier function as revealed by modifications in its
      electrophysiological properties. However, the maturation of the skin functional
      characteristics preceded structural maturation and occurred at stage 8 prior to
      the metamorphic climax. Treatment of Atlantic halibut with the THs disrupter
      methimazole (MMI) affected the number of goblet cells producing neutral mucins
      and the NKA cells. The present study reveals that the asymmetric development of
      the skin in Atlantic halibut is TH sensitive and is associated with metamorphosis
      and that this barrier's functional properties mature earlier and are independent
      of metamorphosis.

PMID- 29464366
TI  - Peritoneal fluid of women with endometriosis reduces SOD1 in bovine oocytes in
      vitro maturation.
AB  - Studies have demonstrated oxidative stress in peritoneal fluid (PF) from women
      with endometriosis and the importance of enzymatic antioxidant machinery to avoid
      oocyte oxidative damage. Considering that PF constantly surrounds the ovaries and
      has direct contact with the oocyte at ovulation, we wonder if PF from women with
      endometriosis may affect antioxidant enzyme gene expression. Thus, the present
      study aims to evaluate the PF impact from infertile women with minimal and mild
      endometriosis and from fertile control women without endometriosis on SOD1, CAT,
      GSR gene's expression in experimental bovine oocytes matured in vitro. Samples of
      PF were obtained from women who underwent videolaparoscopy-7 infertile with EI/II
      and 7 fertile without endometriosis. Immature bovine oocytes underwent in vitro
      maturation in the absence of PF and in the presence of three concentrations (1, 5
      and 10%) of PF from fertile and from infertile women with EI/II. After 22 to 24 h
      of IVM, oocytes were denuded and stored for analysis of SOD1, CAT and GSR by real
      time polymerase chain reaction. Oocyte SOD1 expression was significantly lower in
      the 10% endometriosis group (0.67 +/- 0.32) when compared with no-peritoneal
      fluid (1.05 +/- 0.24, p < 0.008) and 10% control groups (1.06 +/- 0.22, p <
      0.006). These findings raise the possibility of a deleterious influence of PF
      from women with EI/II on the oocyte, not only after ovulation but also during the
      maturation process, which could contribute to worsening oocyte quality, being one
      of the mechanisms related to infertility in patients with endometriosis.

PMID- 29464367
TI  - Inalambric Biofeedback Devices to Analyze Strength Manifestation in Military
      Population.
AB  - The study of the effect of stress on both combatants physiological and anatomical
      systems have been poor studied in the specific literature. The present research
      aimed to study the effect of combat stress in strength manifestations of leg
      flexor-extensor muscles and the anaerobic metabolism of soldiers. Before and
      after asymmetrical combat simulation were analyzed parameters of blood lactate
      concentration, explosive leg strength manifestation and contractile capacity of
      leg muscle in 186 professional soldiers. Results showed a significant increase (p
      < 0.05) in blood lactate values (2.23 +/- 0.95 vs 7.47 +/- 3.67 mmol/L),
      explosive leg strength (Squat Jump 0.31 +/- 0.06 vs 0.35 +/- 0.07 m,
      Countermovement Jump 0.33 +/- 0.07 vs 0.36 +/- 0.07 m, Abalakov Jump 0.39 +/-
      0.08 vs 0.41 +/- 0.09 m), and a significant decrease of the elastic capacity
      (0.022 +/- 0.04 vs 0.021 +/- 0.04) and recruitment and muscle synchronization
      capability (0.028 +/- 0.04 vs 0.026 +/- 0.04). This data suggest that combat
      stress increases the leg strength manifestation despite the significantly
      increase of muscle acidosis after a combat simulation. This result is probably
      due to the high activation of the fight-flight system of soldiers which increases
      the organic response of soldiers and that can compensate the prejudicial effect
      of acidosis in muscle contraction. These results could be used by officers to
      improve specific training programs and to improve planning and election of
      equipment and material for the development of different missions in current
      theaters of operations.

PMID- 29464368
TI  - Correction to: Intra-ligamentary autologous conditioned plasma and healing
      response to treat partial ACL ruptures.
AB  - With regards to Berardo Di Matteo, second author. The author's name is
      incorrectly listed on Pub-Med. The first and last name have been mixed up.

PMID- 29464369
TI  - Bibliometric study of the orthopaedic publications from China.
AB  - PURPOSE: We aimed to investigate the status quo of orthopaedic publications from
      China and characterize the most-cited articles to provide valuable insights for
      orthopaedists. METHODS: PubMed and Embase databases were used to search for
      Chinese orthopaedic publications from 1997 to 2017 to determine the growing
      pattern of Chinese research globally. Then Web of Science database was searched
      for articles with most citations in all journals included in the Journal Citation
      Report 2016 under the category of "orthopaedics" for the last five years, and the
      total numbers of articles in the last three respective years were also analyzed.
      RESULTS: The number of publications published in PubMed and Embase during the
      last 20 years ranged from 218 to 6836, and year 2002 had the biggest growth rate
      of 59.15% and 2014 had the biggest growth value of 1203, comparing with previous
      years. Fifty-three articles were selected as the most-cited ones for the last
      five years. European Spine Journal and West China Hospital are the journal and
      institution that published the most high-impact articles. Majority of the
      articles (47%) were meta-analysis, and 6 RCTs were identified in a total of 11
      clinical articles. Most high-cited clinical articles or meta-analyses were
      classified as level of evidence of I (41.67%).A total of 1238 articles, 1264
      articles, and 1225 articles in the field of orthopedics from China were included
      in SCI for the last three years. CONCLUSION: The Chinese orthopaedic research
      grew rapidly in terms of number of publications in the last decades, and the
      quality of publications also improved in recent years.

PMID- 29464370
TI  - Morphometric evaluation of the knee in Chinese population reveals sexual
      dimorphism and age-related differences.
AB  - PURPOSE: Morphologic data of the knee is very important in the design of total
      knee prostheses. Generally, the designs of the total knee prostheses are based on
      the knee anatomy of Caucasian population. Moreover, in forensic medicine, a
      person's age and sex might be estimated by the shape of their knees. The aim of
      this study is to utilize three-dimensional morphometric analysis of the knee in
      Chinese population to reveal sexual dimorphism and age-related differences.
      MATERIALS AND METHODS: Sexually dimorphic differences and age-related differences
      of the distal femur were studied by using geometric morphometric analysis of ten
      osteometric landmarks on three-dimensional reconstructions of 259 knees in
      Chinese population. General Procrustes analysis, PCA, and other discriminant
      analysis such as Mahalanobis and Goodall's F test were conducted for the knee to
      identify sexually dimorphism and age-related differences of the knee. RESULTS:
      The shape of distal femur between the male and female is significantly different.
      A difference between males and females in distal femur shape was identified by
      PCA; PC1 and PC2 accounted for 61.63% of the variance measured. The correct sex
      was assigned in 84.9% of cases by CVA, and the cross-validation revealed a 81.1%
      rate of correct sex estimation. The osteometric analysis also showed significant
      differences between the three age-related subgroups (< 40, 40-60, > 60 years, p <
      0.005). CONCLUSION: This study showed both sex-related difference and age-related
      difference in the distal femur in Chinese population by 3D geometric morphometric
      analysis. Our bone measurements and geometric morphometric analysis suggest that
      population characteristics should be taken into account and may provide
      references for design of total knee prostheses in a Chinese population. Moreover,
      this reliable, accurate method could be used to perform diachronic and
      interethnic comparisons.

PMID- 29464371
TI  - Risk factor analysis for re-collapse of cemented vertebrae after percutaneous
      vertebroplasty (PVP) or percutaneous kyphoplasty (PKP).
AB  - PURPOSE: Re-collapse of cemented vertebrae occasionally occurs after percutaneous
      augmentation. However, the potential risks still remain unclear. Several articles
      have reported some possible risk factors which were not consistent or
      comprehensive. This study aimed to make a retrospective review on patients with
      osteoporotic vertebral compression fracture (OVCF) after percutaneous
      vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) and to further analyse the
      risk factors for treated vertebral refracture. METHODS: All patients receiving
      the PKP/PVP with bilateral approach were retrospectively reviewed from January
      2014 to January 2016, among whom 230 patients with single level augmentation (30
      in refracture group and 200 in the non-refracture group) were enrolled according
      to inclusion criteria. The following covariates were reviewed: gender, age,
      height, weight, body mass index (BMI), bone mineral density (BMD), serum bone
      turnover markers, surgical parameters including approach, cement volume, anterior
      height, and Cobb angle restoration. Binary logistic regression analysis was used
      to determine the relative risk of re-collapse of cemented vertebrae. RESULTS:
      Regarding the patient data, weight, BMI, and BMD were of statistical significance
      in refracture group (P < 0.01), among which only low BMD was a risk factor to
      cemented vertebral re-collapse (P = 0.022, OR = 4.197). In respect of surgical
      variables, the better restoration of anterior height and Cobb angle was found in
      refracture group (P < 0.05), both of which might increase the refracture risk but
      not be risk factors (P = 0.065, OR = 0.891, and P = 0.937, OR = 0.996,
      respectively). Besides, less injected cement (3.30 +/- 0.84 ml vs 4.46 +/- 1.10
      ml, P = 0.000, OR = 19.433) and PKP (P = 0.007, OR = 13.332) significantly
      boosted the potential risk of refracture (P < 0.001). CONCLUSION: Patients with
      low BMD, or undergoing PKP, or receiving a low volume of injected cement might
      have a high risk of re-collapse in surgical vertebrae.

PMID- 29464372
TI  - Long-term results of total knee arthroplasty after failed high tibial osteotomy.
AB  - PURPOSE: Sometimes, total knee replacement (TKR) is performed after a tibial
      osteotomy. It is not known if the osteotomy influences the clinical process of a
      TKR. The aim of this study was to look at the clinical outcome of a TKR after
      high tibial osteotomy (HTO) compared to a TKR with no HTO. METHODS: Between 1995
      and 2005, 41 post-HTO TKRs (group A) with a minimum follow-up of ten years were
      selected. In parallel, it was selected a control group undergoing simple TKR,
      consisting of 41 patients (group B) matched with group A. The Knee Society Knee
      Score (KS), Knee Score Functional Score (FS), the Oxford Knee Score (OKS), and
      the range of motion (ROM) were used for evaluation at one, five and ten years
      after surgery. The Insall-Salvatti ratio (ISR), the posterior tibial slope (PTS),
      and the joint height line (JHL) were also measured both pre-operatively and post
      operatively. RESULTS: No differences were found between both groups in KS, FS,
      OKS, and ROM at the pre-operative stage or at any of the post-operative controls.
      Higher patellar height was found in group A, both pre-operatively and post
      operatively (p < 0.005), and the same for PTS pre-operative (p < 0.001) and post
      operative (p < 0.05). No differences were found regarding the JHL. Post-operative
      differences were found among the post-HTO subgroups at the FS (p < 0.02), the OKS
      (p < 0.05), and the ROM (p < 0.01) as a function of whether there was a varus or
      a valgus deformity before the TKR. CONCLUSION: A HTO was not determinant for
      having a worse outcome at the TKR, even when there were radiographic differences.
      The coronal alignment with valgus deformity pre-TKR after a HTO showed better
      functional results than in the case of varus deformity. Level of evidence III.

PMID- 29464373
TI  - Early-onset subcortical ischemic vascular dementia in an adult with mtDNA
      mutation 3316G>A.

PMID- 29464374
TI  - Heterogeneous pattern of autonomic dysfunction in Parkinson's disease.
AB  - Dysautonomic symptoms are frequent non-motor complaints in patients with
      Parkinson's disease. Numerous neuropathological studies have shown that Lewy
      bodies and neurites, the pathological hallmarks of Parkinson's disease, are
      widely distributed throughout the peripheral autonomic nervous systems and across
      end organs. However, few investigations integrally explored the symptoms and
      physiology of dysautonomia in Parkinson's disease. We, therefore, performed a
      comprehensive evaluation of the autonomic function in a prospective group of 45
      patients with idiopathic Parkinson's disease. Autonomic components (pupillomotor,
      tear, salivary, cardiovascular, digestive, urinary, sexual, sudomotor functions
      and skin sensitivity) were evaluated using questionnaires and functional tests.
      Skin biopsy was performed for intraepidermal nerve fibre density quantification.
      In addition, all patients underwent polysomnography and a complete
      neuropsychological and neurological assessment. The analysis association of
      autonomic components showed that dysautonomic signs and symptoms were
      heterogeneously distributed among patients. Skin denervation as assessed by
      intraepidermal nerve fibre density quantification was only associated with
      quantitative thermal sensory testing (OR = 12.0, p = 0.02), constipation (OR =
      5.5, p = 0.01) and ocular dryness symptoms (OR = 8.29, p = 0.04). Cognitive
      alteration was associated with cardiovascular symptoms (OR = 4.33, p = 0.03) and
      dysfunction (OR = 5.83, p = 0.02) as well as with constipation (OR = 5.38, p =
      0.02). Axial motor impairment and rapid eye movement (REM) sleep behaviour
      disorder were not related to any of the autonomic complaint or dysfunction. Our
      results show that autonomic functions are affected in a heterogeneous pattern in
      Parkinson's disease, thereby suggesting that the progression of autonomic
      dysfunction follows an erratic rather than a stepwise progression.

PMID- 29464375
TI  - Association between marriage and outcomes in patients with acute ischemic stroke.
AB  - BACKGROUNDS: The previous studies on the association between marital status and
      stroke outcomes were rare. Furthermore, the existing studies mostly focused on
      the protective effect of marriage on survival. We conducted the study to evaluate
      the association between marital status and adverse stroke outcomes in patients
      with AIS based on China national stroke registry. METHODS: This was a
      multicenter, prospective cohort study of patients with AIS. Patients were
      classified into two groups based on marital status at admission: married and
      unmarried. The primary outcomes included all-cause mortality, stroke recurrence,
      combined endpoint, and stroke disability. Stroke disability was defined as
      modified Rankin Scale of 2-6. RESULTS: Of 12,118 patients, 1220 were unmarried
      and 10,898 married. Unmarried patients had higher proportion of 1-year post
      stroke events than married patients did. As compared with being unmarried, the
      adjusted odds ratios with 95% confidence interval of being married for outcomes
      were as follows: 0.70 (0.58-0.84) for all-cause mortality, 0.78 (0.66-0.91) for
      stroke recurrence, 0.77 (0.66-0.90) for combined endpoint, and 0.75 (0.65-0.88)
      for stroke disability. Interactions between marital status and education were
      significant for all outcomes except for stroke disability. CONCLUSIONS: Marital
      status was associated with all adverse stroke outcomes in patients with acute
      ischemic stroke, especially in those with middle-school education.

PMID- 29464376
TI  - In vivo assessment of retinal vessel pathology in amyotrophic lateral sclerosis.
AB  - BACKGROUND: Changes in skin and muscle small blood vessels (SBVs) and
      microvascular structures of the brain have been reported in patients with
      amyotrophic lateral sclerosis (ALS). A direct assessment of brain SBVs in vivo is
      currently not feasible. Retinal vessels are considered a "mirror" of brain SBVs.
      In this study, we used optic coherence tomography (OCT)-based measurements to
      detect changes in retinal blood vessels of ALS patients compared to those of
      healthy controls. METHODS: We analysed Spectralis-OCT images of 34 ALS patients
      and 20 HCs. The inner wall thickness (IWT), outer wall thickness (OWT), and lumen
      diameter (LD) of retinal vessels were assessed using intensity-based
      measurements. In addition, the different retinal layers were analysed using
      automated segmentation software. The correlations between the various retinal
      layers and clinical parameters [e.g., disease duration and revised ALS functional
      rating scale (ALS-FRS-R)] were examined. RESULTS: The OWT of retinal vessels was
      higher in ALS patients than in HCs (p = 0.04). There were no differences in the
      IWT, LD. ALS patients showed a thinning of the outer nuclear layer (ONL) compared
      to HCs (median 1.63 vs. 1.77, p = 0.002). The whole retinal thickness negatively
      correlated with the ALS-FRS scale (r = 0.3, p = 0.03). CONCLUSION: Our study
      reports retinal vessel pathology in ALS patients. These changes may be related to
      those observed in SBVs in skin and muscle biopsies. Furthermore, we report a
      thinning of the ONL in ALS, revealing a possible affection of rods and cones
      function in ALS.

PMID- 29464377
TI  - Is oral feeding compatible with an unresponsive wakefulness syndrome?
AB  - OBJECTIVE: The aim of the study is to explore the possibility of oral feeding in
      unresponsive wakefulness syndrome/vegetative state (UWS/VS) patients. METHOD: We
      reviewed the clinical information of 68 UWS/VS patients (mean age 45 +/- 11;
      range 16-79 years) searching for mention of oral feeding. UWS/VS diagnosis was
      made after repeated behavioural assessments using the Coma Recovery Scale
      Revised. Patients also had complementary neuroimaging evaluations (positron
      emission tomography, functional magnetic resonance imaging and
      electroencephalography and diffusion tensor imaging). RESULTS: Out of the 68
      UWS/VS patients, only two could resume oral feeding (3%). The first patient had
      oral feeding (only liquid and semi liquid) in addition to gastrostomy feeding and
      the second one could achieve full oral feeding (liquid and mixed solid food).
      Clinical assessments concluded that they fulfilled the criteria for a diagnosis
      of UWS/VS. Results from neuroimaging and neurophysiology were typical for the
      first patient with regard to the diagnosis of UWS/VS but atypical for the second
      patient. CONCLUSION: Oral feeding that implies a full and complex oral phase
      could probably be considered as a sign of consciousness. However, we actually do
      not know which components are necessary to consider the swallowing conscious as
      compared to reflex. We also discussed the importance of swallowing assessment and
      management in all patients with altered state of consciousness.

PMID- 29464378
TI  - Smoking at time of CIS increases the risk of clinically definite multiple
      sclerosis.
AB  - BACKGROUND: Cigarette smoking is a modifiable risk factor that influences the
      disease course of patients with multiple sclerosis (MS). However, in patients
      with a clinically isolated syndrome (CIS), there are conflicting results about
      the association between smoking and the risk of a subsequent MS diagnosis. The
      aim of this study was to determine the risk of clinically definite MS (CDMS) in
      smoking and non-smoking patients at time of a first demyelinating event. METHODS:
      Two hundred and fifty patients, aged 18-50 years, were included in our
      prospective CIS cohort. At time of the first neurological symptoms, patients
      completed a questionnaire about smoking habits. Cox regression analyses were
      performed to calculate univariate and multivariate hazard ratios for CDMS
      diagnosis in smoking and non-smoking CIS patients. RESULTS: One hundred and
      fourteen (46%) CIS patients were diagnosed with CDMS during a mean follow-up of
      58 months. In total, 79 (32%) patients smoked at time of CIS. Sixty-seven % of
      the smoking CIS patients were diagnosed with CDMS during follow-up compared to
      36% of the non-smoking CIS patients (p < 0.001). Smoking at time of CIS was an
      independent predictor for CDMS diagnosis (HR 2.3; p = 0.002). Non-smoking CIS
      patients who had a history of smoking did not have a higher risk for CDMS than
      those who had never smoked. CONCLUSIONS: Smoking at time of CIS was an
      independent risk factor for a future CDMS diagnosis. This is an additional
      argument to quit smoking at time of the first attack of suspected MS.

PMID- 29464379
TI  - Positive effects of fampridine on cognition, fatigue and depression in patients
      with multiple sclerosis over 2 years.
AB  - OBJECTIVE: To assess the effects of PR-fampridine on cognitive functioning,
      fatigue and depression in patients with multiple sclerosis (PwMS). METHODS:
      Thirty-two PwMS were included in this trial. Cognitive performance was assessed
      in an open-label and randomized double-blind, placebo-controlled study design
      using a comprehensive neuropsychological test battery as well as questionnaires
      examining depression and fatigue. RESULTS: We found significant improvements in
      cognitive measures assessing alertness (tonic alertness, p = 0.0244 and phasic
      alertness, p = 0.0428), psychomotor speed (p = 0.0140) as well as verbal fluency
      (p = 0.0002) during open-label treatment with PR-fampridine. These effects of
      performance were paralleled by patients' perception of reduced fatigue (physical,
      p = 0.0131; cognitive, p = 0.0225; total, p = 0.0126). Fampridine-induced
      improvements in phasic alertness (p = 0.0010) and measures of fatigue (physical,
      p = 0.0014; cognitive, p = 0.0003; total, p = 0.0005) were confirmed during
      randomized, double-blind, placebo-controlled assessment in the second year. In
      addition, we found positive effects of PR-fampridine on depressive symptoms (p =
      0.0049). We demonstrated persisting beneficial effects of PR-fampridine on
      fatigue in PwMS over a period of more than 2 years. Drug responsiveness regarding
      cognitive performance and fatigue was not limited to walking responders.
      CONCLUSIONS: Our data demonstrate significant positive effects of treatment with
      PR-fampridine over 2 years on different cognitive domains as well as fatigue and
      depression in a cohort of PwMS. These findings imply that PR-fampridine should be
      considered as symptomatic treatment improving aspects of cognition, fatigue and
      depression in PwMS.

PMID- 29464381
TI  - Is mental time embodied interpersonally?
AB  - Recent evidence has shown that the mental representation of time is "embodied"
      time is expressed via the hands, the eyes, and the whole body. These findings
      suggest the existence of a manually reflected mental time line running (in
      Western culture) horizontally from left (past) to right (future) and an ocularly
      reflected mental time line running from left/down (past) to right/up (future). We
      addressed the question whether mental time is also reflected interpersonally and
      investigated whether an avatar's face orientation (left vs. right) would
      facilitate a subject's temporal processing in relation to the horizontal mental
      time line. In combination with a left- or right-gazing avatar, we presented a
      temporal auditory word ("gestern"-yesterday or "morgen"-tomorrow), and our
      subjects had to manually categorize the word as being either past- or future
      related (classic left/right key-press paradigm). The stimulus-response (SR)
      mapping was either compatible (past word-left hand, future word-right hand) or
      incompatible (future word-left hand, past word-right hand). Responses were
      significantly faster in blocks with compatible versus incompatible mapping. Thus,
      our results provide clear evidence for manually reflected mental time running
      from left to right, even for temporal auditory words that are free of potential
      visual (reading direction) confounds. The presented interpersonal cues (avatar
      head orientation) facilitated the activation of the horizontal mental time line
      in blocks with incompatible SR-mapping but not in blocks with compatible
      (standard) mapping. We conclude that interpersonal cues exert weak effects on the
      spatial representation of mental time and can help to adapt context-specific
      mappings of temporal concepts.

PMID- 29464382
TI  - Repair of the Severe Muscle Aponeurotic Abdominal Laxity with Alloplastic Mesh in
      Aesthetic Abdominoplasty.
AB  - BACKGROUND: Abdominoplasty is the most frequently performed surgical procedure
      for body contour; in our experience, we have observed some patients with
      prominent bulging that is difficult to treat and that presents results that are
      unsatisfactory or have recurrences to conventional treatments. This leads us to
      carry out an analysis of the elements responsible for the containment and
      abdominal format. We determined that it may be due to an inability of an
      important sagging aponeurotic muscle of primary origin to support the abdomen and
      could be caused by predisposing factors. For these specific cases, we developed a
      treatment proposing the use of a mesh. METHODS: We present these cases over a
      period of 24 years. Fourteen patients were treated with primary and secondary
      abdominoplasties. The abdominal wall reinforcement was performed by placing
      polypropylene mesh at the sub-muscular plane, fixed with U-stitches on the fascia
      transversalis, seeking to strengthen the muscle and the fascia transversalis.
      RESULTS: The results were satisfactory after long-term observation, gaining
      resolution of the abdominal bulges. Only two complications occurred; the presence
      of localized chronic pain and the appearance of umbilical fistula. DISCUSSION: We
      emphasize the importance of avoiding unnecessary interventions in patients with
      marked bulging, associated with inability of abdominal restraint. We only
      consider its indications in patients with conventional recurrence treatment, also
      identifying the predisposing factors, the knowledge of the abdominal anatomy, the
      muscular dynamics of the abdomen and understanding its indication in these
      specific cases of difficult treatment. 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- 29464380
TI  - The metabolic and endocrine characteristics in spinal and bulbar muscular
      atrophy.
AB  - OBJECTIVE: Spinal and bulbar muscular atrophy (SBMA) is caused by an abnormal
      expansion of the CAG repeat in the androgen receptor gene. This study aimed to
      systematically phenotype a German SBMA cohort (n = 80) based on laboratory
      markers for neuromuscular, metabolic, and endocrine status, and thus provide a
      basis for the selection of biomarkers for future therapeutic trials. METHODS: We
      assessed a panel of 28 laboratory parameters. The clinical course and blood
      biomarkers were correlated with disease duration and CAG repeat length. A subset
      of 11 patients was evaluated with body fat MRI. RESULTS: Almost all patients
      reported muscle weakness (99%), followed by dysphagia (77%), tremor (76%), and
      gynecomastia (75%) as major complaints. Creatine kinase was the most consistently
      elevated (94%) serum marker, which, however, did not relate with either the
      disease duration or the CAG repeat length. Paresis duration and CAG repeat length
      correlated with dehydroepiandrosterone sulfate after correction for body mass
      index and age. The androgen insensitivity index was elevated in nearly half of
      the participants (48%). CONCLUSIONS: Metabolic alterations in glucose homeostasis
      (diabetes) and fat metabolism (combined hyperlipidemia), and sex hormone
      abnormalities (androgen insensitivity) could be observed among SBMA patients
      without association with the neuromuscular phenotype. Dehydroepiandrosterone
      sulfate was the only biomarker that correlated strongly with both weakness
      duration and the CAG repeat length after adjusting for age and BMI, indicating
      its potential as a biomarker for both disease severity and duration and,
      therefore, its possible use as a reliable outcome measure in future therapeutic
      studies.

PMID- 29464383
TI  - Concentric Malar Lift in the Management of Lower Eyelid Rejuvenation or
      Retraction: A Clinical Retrospective Study on 342 Cases, 13 Years After the First
      Publication.
AB  - BACKGROUND: Lower eyelid rejuvenation can, unfortunately, induce scleral show
      even if the lower eyelid procedure is limited. This study was designed to assess
      the effectiveness and reliability of the concentric malar lift technique in two
      scenarios: the first, in rejuvenation of the mid-face and, the second, in
      reconstructive surgery for correction of congenital or acquired eyelids
      malposition. METHODS: The concentric malar lift technique was first published by
      Le Louarn (Aesthet Plast Surg 28(6):359-372, 2004). This retrospective study was
      carried out by analyzing data on patients operated on between January 2010 and
      January 2016. Patients operated on before 2010 were excluded because barbed
      thread sutures were not used in the first version of the technique. Patients
      after January 2016 were excluded to ensure adequate follow-up, and so 342
      patients are included in the study. A total of 256 cases (75%) were for aesthetic
      mid-face lifting, and 86 cases (25%) were reconstructive surgeries for lower
      eyelid retraction. A spacer graft was used in 30 of these reconstructive cases
      (35%). The mean follow-up time was 13.6 months. All the concentric malar lifting
      procedures included strengthening the lateral canthus, which is a key element of
      the procedure. RESULTS: None of the patients developed secondary eyelid
      malposition, and all the cases of lower eyelid retraction displayed marked
      improvement both functionally and aesthetically. Two patients experienced loss of
      sensitivity of part in the infra-orbital nerve distribution for 4 months after
      the procedure. CONCLUSION: The concentric malar lift procedure enables the
      recruitment of a significant amount of skin into the lower eyelid: between 10 and
      30 mm. It ensures better rejuvenation of the mid-face with minimal risk of lower
      eyelid malposition. In reconstruction of the lower eyelid lid, the concentric
      malar lift is able to reduce the need for skin grafting and a skin flap reducing
      the risks of visible scarring. 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- 29464384
TI  - Versajet-Assisted Hydraulic Epilation Through Small Incisions for Axillary
      Osmidrosis.
AB  - BACKGROUND: Osmidrosis is a malodorous disease caused by the breakdown of sweat
      secreted from the apocrine glands by surface bacteria. The aim of this study was
      to evaluate the effect of Versajet-assisted hydraulic epilation for the treatment
      of axillary osmidrosis. METHODS: Thirty-two patients with axillary osmidrosis (64
      axillae) underwent Versajet-assisted hydraulic epilation between January 2016 and
      January 2017. Subjective assessments were evaluated by a patient survey at least
      3 months after the procedure. RESULTS: There were no complications other than one
      mild pigmentation in the axilla at 3 months after the procedure. Thirty-two
      patients evaluated malodor elimination as good. No patients evaluated it as fair
      or poor. There were no recurrences. CONCLUSION: Versajet-assisted hydraulic
      epilation is an ideal surgical procedure for the treatment of axillary osmidrosis
      that decreases complications and recurrence. 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- 29464385
TI  - Prevention of Emergence Agitation with Ketamine in Rhinoplasty.
AB  - BACKGROUND: Emergence agitation (EA), defined as restlessness, disorientation,
      excitation, and/or inconsolable crying, is a common phenomenon during early
      recovery from general anesthesia. In this study, we aimed to determine the (1) EA
      incidence after rhinoplasty operations in adults; (2) the effects of ketamine
      administered at sub-anesthetic doses just 20 min before the end of the surgery in
      rhinoplasty operations on agitation level, postoperative pain, side effects, and
      complications; and (3) to determine the risk factors for EA in adults after
      rhinoplasty. MATERIALS AND METHODS: Totally 140 patients scheduled to undergo
      elective rhinoplasty were enrolled in this prospective study. Patients were
      equally and randomly divided into two groups: saline group (control group) (n =
      70) and ketamine group (n = 70). Twenty minutes before surgery completion, 1 ml
      saline was administered via the intravenous (i.v.) route to the saline group,
      while 0.5 mg/kg ketamine was administered via i.v. patients in the ketamine
      group. The emergence agitation level of the patients was evaluated using the
      Richmond Agitation-Sedation Scale just after extubation and in the post
      anesthesia care unit (PACU). For postoperative pain evaluation, the Numerical
      Rating Scale (NRS) was scored (from 0 to 10) every 10 min until the patients were
      discharged from PACU. RESULTS: EA incidence in the control group was as high as
      54.3%, while in the ketamine group it was 8.6% just after extubation (p < 0.001).
      In the PACU, EA incidence was 28.6% in the control group, while none of the
      patients had EA in the PACU in the ketamine group (p < 0.001). Male gender,
      severe pain (NRS >= 5), and smoking were defined as significant risk factors for
      EA both after extubation and during follow-ups in the PACU (p < 0.001).
      CONCLUSIONS: Emergence agitation after rhinoplasty is a common complication,
      likely disturbing operative outcomes in adults. Ketamine at sub-anesthetic doses
      is highly effective in preventing EA. Further, larger-scale prospective studies
      are warranted to determine preventive measures for EA development in rhinoplasty.
      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- 29464386
TI  - Clinical Characteristics of Asymmetric Bilateral Gynecomastia: Suggestion of
      Desirable Surgical Method Based on a Single-Institution Experience.
AB  - BACKGROUND: Asymmetric bilateral gynecomastia (ABGM) is uncommon, and reports on
      its characteristics are rare. In the present study, we investigated the clinical
      characteristics and surgical treatment of ABGM. METHODS: We conducted a
      retrospective study of 1159 patients with gynecomastia who underwent subcutaneous
      mastectomy with liposuction at Damsoyu Hospital from January 2014 to February
      2016. We then analyzed differences in the characteristics and operative results
      between two groups of patients: those with asymmetric and symmetric gynecomastia.
      Asymmetric gynecomastia was defined as gynecomastia meeting both of the following
      criteria: (1) upon physical examination, the size of the palpable mass below the
      nipple-areolar complex was twice as large as the smaller one, and (2) upon
      ultrasonography, the depth of the glandular tissue under the nipple-areolar
      complex was twice as large as the smaller one. RESULTS: Fifty-four patients were
      diagnosed with asymmetric gynecomastia. Among them, 51 had ABGM and three had
      unilateral gynecomastia. In the asymmetric group, more patients had a larger left
      than right breast (33 patients, 64.7%). The incidence of true-type (entirely
      glandular) breasts was significantly higher in the asymmetric group (84.3%) than
      in the symmetric group (p < 0.001). The asymmetry ratios in the asymmetric and
      symmetric groups were 1.87 +/- 2.07 and 0.20 +/- 0.16, respectively (p < 0.001).
      CONCLUSION: Bilateral mastectomy provided an acceptable and symmetric cosmetic
      outcome in patients with ABGM. 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- 29464387
TI  - Influence of hydrogen bonds on edge-to-face interactions between pyridine
      molecules.
AB  - Edge-to-face interactions between two pyridine molecules and the influence of
      simultaneous hydrogen bonding of one or both of the pyridines to water on those
      interactions were studied by analyzing data from ab initio calculations. The
      results show that the edge-to-face interactions of pyridine dimers that are
      hydrogen bonded to water are generally stronger than those of non-H-bonded
      pyridine dimers, especially when the donor pyridine forms a hydrogen bond. The
      binding energy of the most stable edge-to-face interacting H-bonded pyridine
      dimer is -5.05 kcal/mol, while that for the most stable edge-to-face interacting
      non-H-bonded pyridine dimer is -3.64 kcal/mol. The interaction energy data
      obtained in this study cannot be explained solely by the differences in
      electrostatic potential between pyridine and the pyridine-water dimer. However,
      the calculated cooperative effect can be predicted using electrostatic potential
      maps.

PMID- 29464388
TI  - Simultaneous bone remodeling and surgical decompression of large Sylvian
      arachnoid cyst.
AB  - The most common location for intracranial arachnoid cysts is the region of the
      Sylvian fissure, where they can be found in 49% of cases. Management of these
      cysts is still quite controversial. We present our surgical technique for the
      treatment of large Sylvian fissure arachnoid cysts which involves cyst
      decompression and simultaneous calvarial remodeling. After decreasing cyst size,
      remodeling of the frontal, temporal, and parietal bones follows. The cyst itself
      is treated with a cystoperitoneal shunt. In immediate postoperative period,
      correction of the deformity is observed. The cyst volume is reduced immediately
      after surgery, and adequate adaptation of the bone is achieved. Our surgical
      procedure for simultaneous bone remodeling and cyst decompression is a fast,
      simple, and effective treatment option for patients with large Sylvian fissure
      arachnoid cysts associated with significant cranial disfigurement. We consider
      cranial remodeling in case of large arachnoid cyst important not just because of
      the cosmetic result but also for reducing remaining intracranial space filled
      with cerebrospinal fluid. It may be an important factor to reduce the risk of
      intracystic and subdural hemorrhage. It is a widely applicable procedure that
      does not require special tools and expensive equipment, and yet it can help avoid
      multiple surgeries and complications tied to them.

PMID- 29464389
TI  - Patient-reported outcome measures in a pharmacokinetic study with sunitinib, a
      prospective cohort study.
AB  - PURPOSE: During treatment with tyrosine kinase inhibitors, such as sunitinib,
      patients experience treatment and/or disease-related symptoms. Although
      application of patient-reported outcome measures (PROMs) enhances early
      recognition of symptoms, early clinical trials are focused on symptom severity
      objectified by the Common Terminology Criteria for Adverse Events (CTCAE) in
      order to evaluate drug safety and to determine a personalized and/or safe dosage
      range. To gain insight into patient-reported symptoms in addition to healthcare
      professional-reported adverse events (AEs), a substudy was conducted in an
      ongoing pharmacokinetic-guided sunitinib dosing study. METHODS: In patients for
      whom sunitinib was considered standard therapy or patients with
      advanced/metastatic tumors for whom no standard therapy was available, patient
      reported symptoms and well-being besides healthcare professional-reported AEs
      were assessed. RESULTS: Twenty-nine patients were included for analysis. Over 50%
      of them experienced a decreased well-being, caused by symptoms of mild and
      moderate intensity. Compared to healthcare professionals, all measured symptoms,
      with the exception of fatigue and vomiting, were reported statistically
      significantly more often by patients. CONCLUSIONS: Application of PROMs in early
      clinical trials on personalized or individualized oral targeted anticancer agents
      is feasible and enhances early recognition of symptom burden due to multiple
      CTCAE grade 1-2 AEs, just as pro-active symptom management and effect evaluation
      of interventions performed. Application of PROMs in these trials might be
      clinically relevant in obtaining dose-limiting toxicities.

PMID- 29464390
TI  - Bariatric Surgery Prior to Total Joint Arthroplasty, Does it Decrease the Risk of
      Obesity Related Perioperative Complications?
AB  - PURPOSE OF REVIEW: The purpose of this review paper is to provide an overview of
      the relationship between obesity, osteoarthritis, arthroplasty outcomes, and the
      potential use of bariatric surgery to improve these outcomes. RECENT FINDINGS:
      Unfortunately, the findings in the currently available literature evaluating the
      role of bariatric surgery prior to arthroplasty surgery largely rely on
      retrospective data and their results are somewhat conflicting. Future prospective
      studies are needed to further evaluate whether or not bariatric surgery prior to
      arthroplasty surgery may be of benefit for patients. Additional research is
      needed to identify other methods to minimize complications that obese patients
      are particularly prone to developing following arthroplasty surgery.

PMID- 29464391
TI  - Treatment of Pediatric Pulmonary Hypertension.
AB  - Pulmonary hypertension (PH) is an increasingly recognized problem in children,
      particularly within tertiary pediatric hospitals. This increase is, in large
      part, due to ever improving survival among previously fatal conditions, such as
      extreme prematurity and complicated congenital heart disease. This increased
      recognition has paralleled burgeoning pharmacologic and interventional PH
      specific treatment options. Unfortunately, most PH-specific therapies have not
      been tested in children with rigorous, randomized, controlled trials. As a
      result, most treatment of PH in children is based upon expert consensus and
      practitioners' experience. In this article, we highlight some of the current and
      recent advances in therapies available for children with PH. The role that a
      Potts shunt may have in ameliorating severe PH in children is highlighted.

PMID- 29464392
TI  - Posterior subdeltoid and external rotators preserving approach for reduction and
      fixation of displaced extra-articular fractures of the scapula.
AB  - BACKGROUND: Operative management of scapular body fractures, when indicated,
      typically involves extensive exposure through a posterior approach. We present
      our experience with a deltoid preserving approach that allows excellent exposure
      of the fracture lines for reduction and fixation while minimizing muscle
      detachment and overall tissue trauma. TECHNIQUE: Exposure of the scapula was
      obtained through a posterior incision. The posterior deltoid was exposed and
      retracted superiorly while the arm was abducted in accordance with Brodsky et al.
      The scapula was exposed in the interval between infraspinatus and teres minor.
      PATIENTS AND METHODS: Six patients were treated using this approach and were
      retrospectively reviewed. All were men with a mean age of 34 years (range 24-45
      +/- 6.7 years). The injuries involved two 14-A3.1 and four 14-A3.2 AO/OTA types
      of fractures. The mean follow-up after surgery was 28 months (range 21-36 +/-
      4.93 months). RESULTS: All fractures could be anatomically reduced and healed
      without compromise. The mean Constant score was 93.8 (range 91-97 +/- 2.13),
      while range of motion and strength returned to levels equal to the uninjured
      shoulder. All patients returned to their previous level of activity. We did not
      observe atrophy of the posterior muscles or hardware complications, and none
      required hardware removal. CONCLUSION: The deltoid and external rotators
      preserving posterior approach permitted good visualization of the fractures while
      allowing reduction and fixation without extensive muscular dissection and
      provided excellent functional outcomes. We consider that it offers obvious
      advantages over more aggressive muscle detaching approaches. LEVEL OF EVIDENCE:
      Therapeutic study, IV.

PMID- 29464394
TI  - Functional dissection of the three N-terminal general secretory pathway domains
      and the Walker motifs of the traffic ATPase PilF from Thermus thermophilus.
AB  - The traffic ATPase PilF of Thermus thermophilus powers pilus assembly as well as
      uptake of DNA. PilF differs from other traffic ATPases by a triplicated general
      secretory pathway II, protein E, N-terminal domain (GSPIIABC). We investigated
      the in vivo and in vitro roles of the GSPII domains, the Walker A motif and a
      catalytic glutamate by analyzing a set of PilF deletion derivatives and pilF
      mutants. Here, we report that PilF variants devoid of the first two or all three
      GSPII domains do not form stable hexamers indicating a role of the triplicated
      GSPII domain in complex formation and/or stability. A pilFDeltaGSPIIC mutant was
      significantly impaired in piliation which leads to the conclusion that the GSPIIC
      domain plays a vital role in pilus assembly. Interestingly, the pilFDeltaGSPIIC
      mutant was hypertransformable. This suggests that GSPIIC strongly affects
      transformation efficiency. A pilF?GSPIIA mutant exhibited wild-type piliation but
      reduced pilus-mediated twitching motility, suggesting that GSPIIA plays a role in
      pilus dynamics. Furthermore, we report that pilF mutants with a defect in the ATP
      binding Walker A motif or in the catalytic glutamate residue are defective in
      piliation and natural transformation. These findings show that both, ATP binding
      and hydrolysis, are essential for the dual function of PilF in natural
      transformation and pilus assembly.

PMID- 29464395
TI  - Temporal Trends of Pediatric Dysphagia in Hospitalized Patients.
AB  - The objective of this study was to determine temporal trends of dysphagia
      diagnoses in hospitalized children. This is a retrospective observational study
      from the 1997-2012 Kids' Inpatient Database (KID) conducted in the setting of
      weighted hospitalizations in a KID participating center. More than 6 million
      pediatric admissions were captured in each triennial KID report. Main outcomes
      included triennial rates of dysphagia diagnosis in hospitalized pediatric
      patients, and secondary outcomes included rates of dysphagia in premature and low
      birthweight infants. Dysphagia diagnoses were coded in 5107/6607653 (0.08%) of
      these admissions in 1997, rising to 27,464/6,675,222 (0.41%) in 2012 (p < 0.001).
      The portion of these diagnoses in premature neonates has been increasing over
      time from 162/9551 (1.7%) in 2003 to 1027/27,464 (3.7%) by 2012 (p < 0.001).
      Similarly, low-birthweight children constituted 40/5107 (0.8%) of dysphagia
      diagnoses in 1997, a number that increased to 762/27,464 (2.8%) in 2012. Rates of
      dysphagia are increasing nationally, particularly in premature and low
      birthweight infants, which may represent an increase alongside other
      neuroanatomic abnormalities. This growing problem illustrates the need for better
      data on the comparative efficacy of diagnostic and treatment modalities.

PMID- 29464393
TI  - Knockdown of STEAP1 inhibits cell growth and induces apoptosis in LNCaP prostate
      cancer cells counteracting the effect of androgens.
AB  - Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is overexpressed
      in numerous types of tumors, especially in prostate cancer. STEAP1 is located in
      the plasma membrane of epithelial cells and may play an important role in inter-
      and intracellular communication. Several studies suggest STEAP1 as a potential
      biomarker and an immunotherapeutic target for prostate cancer. However, the role
      of STEAP1 in cell proliferation and apoptosis remains unclear. Therefore, the
      role of STEAP1 in prostate cancer cells proliferation and apoptosis was
      determined by inducing STEAP1 gene knockdown in LNCaP cells. In addition, the
      effect of DHT on the proliferation of LNCaP cells knocked down for STEAP1 gene
      was evaluated. Our results demonstrated that silencing the STEAP1 gene reduces
      LNCaP cell viability and proliferation, while inducing apoptosis. In addition, we
      showed that the cellular and molecular effects of STEAP1 gene knockdown may be
      independent of DHT treatment, and blocking STEAP1 may reveal to be an appropriate
      strategy to activate apoptosis in cancer cells, as well as to prevent the
      proliferative and anti-apoptotic effects of DHT in prostate cancer.

PMID- 29464396
TI  - Phase I study of primary treatment with 5-FU, oxaliplatin, irinotecan,
      levofolinate, and panitumumab combination chemotherapy in patients with
      advanced/recurrent colorectal cancer involving the wild-type RAS gene: the JACCRO
      CC-14 study.
AB  - BACKGROUND: FOLFOXIRI is now regarded as the chemotherapy regimen that offers the
      best platform for the treatment of colorectal cancer. However, the safety and
      efficacy of FOLFOXIRI + panitumumab has not been demonstrated. We conducted a
      phase I study to determine the recommended dose of FOLFOXIRI + panitumumab as
      first-line treatment for RAS wild-type metastatic colorectal cancer (mCRC).
      METHODS: Patients received combination therapy consisting of panitumumab (6 mg/kg
      on day 1) + FOLFOXIRI [irinotecan (CPT-11), oxaliplatin (L-OHP) 85 mg/m2, and
      folinate (LV) 200 mg/m2] on day 1, followed by fluorouracil (5-FU) 3200 mg/m2
      infused as a 46-h continuous infusion starting on day 1) repeated every 2 weeks
      as first-line treatment of RAS wild-type mCRC patients. A decrease in CPT-11 dose
      was planned (started at level 1: CPT-11 165 mg/m2). RESULTS: Seven patients were
      enrolled, and six were assessed for safety and efficacy. Maximum tolerated dose
      was not reached at level 1; all patients were treated at these levels. The common
      Grade 3 or 4 relevant toxicities were diarrhea (50%), hypokalemia (33%) and
      stomatitis (33%). No treatment-related deaths occurred. Of the six patients
      assessed four had partial response and the two others had stable disease; hence,
      the response rate was 66.7% (95% confidence interval 28.9-100%) and the disease
      control rate was 100%. Time to protocol treatment failure was 7.2 (1.4-7.3)
      months. CONCLUSION: The FOLFOXIRI + panitumumab chemotherapy regimen was well
      tolerated by our patients with mCRC and showed promising anti-tumor activity. The
      recommended phase II dose was determined to be the same as the standard doses of
      this regimen used worldwide.

PMID- 29464397
TI  - Mining Protein Evolution for Insights into Mechanisms of Voltage-Dependent Sodium
      Channel Auxiliary Subunits.
AB  - Voltage-gated sodium channel (VGSC) beta (beta) subunits have been called the
      "overachieving" auxiliary ion channel subunit. Indeed, these subunits regulate
      the trafficking of the sodium channel complex at the plasma membrane and
      simultaneously tune the voltage-dependent properties of the pore-forming alpha
      subunit. It is now known that VGSC beta-subunits are capable of similar
      modulation of multiple isoforms of related voltage-gated potassium channels,
      suggesting that their abilities extend into the broader voltage-gated channels.
      The gene family for these single transmembrane immunoglobulin beta-fold proteins
      extends well beyond the traditional VGSC beta1-beta4 subunit designation, with
      deep roots into the cell adhesion protein family and myelin-related proteins -
      where inherited mutations result in a myriad of electrical signaling disorders.
      Yet, very little is known about how VGSC beta-subunits support protein
      trafficking pathways, the basis for their modulation of voltage-dependent gating,
      and, ultimately, their role in shaping neuronal excitability. An evolutionary
      approach can be useful in yielding new clues to such functions as it provides an
      unbiased assessment of protein residues, folds, and functions. An approach is
      described here which indicates the greater emergence of the modern beta-subunits
      roughly 400 million years ago in the early neurons of Bilateria and bony fish,
      and the unexpected presence of distant homologues in bacteriophages. Recent
      structural breakthroughs containing alpha and beta eukaryotic sodium channels
      containing subunits suggest a novel role for a highly conserved polar contact
      that occurs within the transmembrane segments. Overall, a mixture of approaches
      will ultimately advance our understanding of the mechanism for beta-subunit
      interactions with voltage-sensor containing ion channels and membrane proteins.

PMID- 29464398
TI  - Discussions about predictive genetic testing for Lynch syndrome: the role of
      health professionals and families in decisions to decline.
AB  - Unaffected relatives of individuals with Lynch syndrome can be offered predictive
      genetic testing to guide surveillance recommendations. The decision-making
      process of those who decline testing, particularly those who do not attend a
      clinical genetics service, is poorly understood. We have addressed this gap by
      interviewing 33 individuals from Lynch syndrome mutation-carrying families,
      unaffected by cancer, who declined predictive genetic testing. Here, we analyse
      the data provided by 20 participants who unequivocally declined testing. Those
      who indicated they did not have enough information to make a decision or intended
      to undergo testing in the future were excluded. Analysis revealed that few
      decliners discussed their decision with general practitioners or genetic
      counsellors. Family members were commonly involved to varying degrees, with
      participants either (1) making group decisions with family members, (2) feeling
      persuaded by family members to either accept or decline testing, (3) discussing
      the test but making their own decision. A minority did not discuss testing with
      family members while making their decision. This research reveals the health
      communication activities of an understudied group, those declining predictive
      testing, and indicates that for many, health professionals play a minor role in
      the decision compared to family.

PMID- 29464400
TI  - Monitoring and assessment of urban growth patterns using spatio-temporal built-up
      area analysis.
AB  - The identification of spatio-temporal patterns of the urban growth phenomenon has
      become one of the most significant challenges in monitoring and assessing current
      and future trends of the urban growth issue. Therefore, spatio-temporal and
      quantitative techniques should be used hand in hand for a deeper understanding of
      various aspects of urban growth. The main purpose of this study is to monitor and
      assess the significant patterns of urban growth in Seremban using a spatio
      temporal built-up area analysis. The concentric circles approach was used to
      measure the compactness and dispersion of built-up area by employing Shannon's
      Entropy method. The spatial directions approach was also utilised to measure the
      sustainability and speed of development, while the gradient approach was used to
      measure urban dynamics by employing landscape matrices. The overall results
      confirm that urban growth in Seremban is dispersed, unbalanced and unsustainable
      with a rapid speed of regional development. The main contribution of using
      existing methods with other methods is to provide several spatial and statistical
      dimensions that can help researchers, decision makers and local authorities
      understand the trend of growth and its patterns in order to take the appropriate
      decisions for future urban planning. For example, Shannon's Entropy findings
      indicate a high value of dispersion between the years 1990 and 2000 and from 2010
      to 2016 with a growth rate of approximately 94 and 14%, respectively. Therefore,
      these results can help and support decision makers to implement alternative urban
      forms such as the compactness form to achieve an urban form that is more suitable
      and sustainable. The results of this study confirm the importance of using spatio
      temporal built-up area and quantitative analysis to protect the sustainability of
      land use, as well as to improve the urban planning system via the effective
      monitoring and assessment of urban growth trends and patterns.

PMID- 29464399
TI  - Segmental isotopic labeling of HIV-1 capsid protein assemblies for solid state
      NMR.
AB  - Recent studies of noncrystalline HIV-1 capsid protein (CA) assemblies by our
      laboratory and by Polenova and coworkers (Protein Sci 19:716-730, 2010; J Mol
      Biol 426:1109-1127, 2014; J Biol Chem 291:13098-13112, 2016; J Am Chem Soc
      138:8538-8546, 2016; J Am Chem Soc 138:12029-12032, 2016; J Am Chem Soc 134:6455
      6466, 2012; J Am Chem Soc 132:1976-1987, 2010; J Am Chem Soc 135:17793-17803,
      2013; Proc Natl Acad Sci USA 112:14617-14622, 2015; J Am Chem Soc 138:14066
      14075, 2016) have established the capability of solid state nuclear magnetic
      resonance (NMR) measurements to provide site-specific structural and dynamical
      information that is not available from other types of measurements. Nonetheless,
      the relatively high molecular weight of HIV-1 CA leads to congestion of solid
      state NMR spectra of fully isotopically labeled assemblies that has been an
      impediment to further progress. Here we describe an efficient protocol for
      production of segmentally labeled HIV-1 CA samples in which either the N-terminal
      domain (NTD) or the C-terminal domain (CTD) is uniformly 15N,13C-labeled.
      Segmental labeling is achieved by trans-splicing, using the DnaE split intein.
      Comparisons of two-dimensional solid state NMR spectra of fully labeled and
      segmentally labeled tubular CA assemblies show substantial improvements in
      spectral resolution. The molecular structure of HIV-1 assemblies is not
      significantly perturbed by the single Ser-to-Cys substitution that we introduce
      between NTD and CTD segments, as required for trans-splicing.

PMID- 29464401
TI  - Pathological outcomes of transanal versus laparoscopic total mesorectal excision
      for rectal cancer: a systematic review with meta-analysis.
AB  - BACKGROUND: Since 2010, comparative studies on transanal and laparoscopic total
      mesorectal excision (TME) have been published and it remains unclear about the
      oncological benefit from transanal total mesorectal excision (taTME). METHODS: We
      have searched English databases to identify all taTME studies published between
      January 2010 and August 2017. Pathological outcomes included circumferential
      resection margin (CRM), positive CRM (< 1 M), length of distal resection margin
      (DRM), positive DRM, quality of mesorectum (complete mesorectum), harvested lymph
      node, and length of the specimen. Odds ratios (ORs) were calculated for
      dichotomous outcomes and weighted mean differences (WMDs) for continuous
      outcomes. RESULTS: We have included ten studies comprising of 762 patients.
      Compared with laparoscopic TME, taTME had a longer CRM (WMD, 0.833; 95% CI 0.366
      1.299; P < 0.001), a lower positive rate of CRM (OR, 0.505; 95% CI 0.258-0.991; P
      = 0.047), and a longer DRM (WMD, 6.261; 95% CI 1.049-11.472; P = 0.019). There
      were no significant differences in other pathological outcomes. Both cumulative
      meta-analysis and sensitivity analysis were unable to detect potential sources of
      the heterogeneity in DRM. There was no evidence of publication bias. CONCLUSIONS:
      This meta-analysis revealed that taTME had more advantages on positive CRM, CRM,
      and DRM compared with laparoscopic TME. Compared with laparoscopic TME, more
      benefits of taTME on pathological outcomes remained undetected. The current
      findings are all based on observational studies, RCTs with adequate power are
      required.

PMID- 29464402
TI  - Clinical outcomes of minimally invasive treatment for early gastric cancer in
      patients beyond the indications of endoscopic submucosal dissection.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) with laparoscopic sentinel
      lymph node dissection (ESN) and endoscopic full-thickness gastric resection with
      laparoscopic sentinel lymph node dissection (Hybrid-natural orifice transluminal
      endoscopic surgery, Hybrid-NOTES) are minimally invasive treatment options for
      early gastric cancer (EGC) beyond the indications of ESD. This study aimed to
      evaluate the short- and long-term clinical outcomes of ESN and Hybrid-NOTES.
      METHODS: We retrospectively analyzed patients who had undergone ESN or Hybrid
      NOTES for EGC from January 2009 to March 2013. A total of 48 patients, including
      21 undergoing ESN and 27 undergoing Hybrid-NOTES, were enrolled. All patients had
      cancer stage T1N0M0, EGC less than 5 cm in size, and suspected submucosal
      invasion according to imaging or biopsy-proven diffuse-type histology. RESULTS:
      In ESN and Hybrid-NOTES, the curative resection rates were 76.5% and 90.9% of
      patients, respectively. In the ESN group, 5 patients underwent an additional
      gastrectomy (1 for lymph node metastasis (LNM), 3 for surgical complications, and
      1 for noncurative resection). In the Hybrid-NOTES group, 6 patients underwent
      additional gastrectomy, (1 for LNM, 3 for surgical complications, and 2 for
      noncurative resection). Of the 37 patients who were followed up in the long-term
      (a median follow-up of 59.8 months), one was found to have liver metastasis after
      ESN and received palliative chemotherapy. CONCLUSIONS: ESN and Hybrid-NOTES have
      shown favorable long-term outcomes despite their technical limitations. These
      methods may be utilized as a bridge between ESD and gastrectomy in cases of EGC
      with a high risk of LNM beyond the ESD indications.

PMID- 29464403
TI  - Assessment of snow-glacier melt and rainfall contribution to stream runoff in
      Baspa Basin, Indian Himalaya.
AB  - Hydrological regimes of most of the Himalayan river catchments are poorly studied
      due to sparse hydro-meteorological data. Hence, stream runoff assessment becomes
      difficult for various socio-industrial activities in the Himalaya. Therefore, an
      attempt is made in this study to assess the stream runoff of Baspa River in
      Himachal Pradesh, India, by evaluating the contribution from snow-ice melt and
      rainfall runoff. The total volume of flow was computed for a period of 15 years,
      from 2000 to 2014, and validated with the long-term field discharge measurements,
      obtained from Jaipee Hydropower station (31 degrees  32' 35.53" N, 78 degrees 
      00' 54.80" E), at Kuppa barrage in the basin. The observations suggest (1) a good
      correlation (r2 > 0.80) between the modeled runoff and field discharge
      measurements, and (2) out of the total runoff, 81.2% are produced by snowmelt,
      11.4% by rainfall, and 7.4% from ice melt. The catchment receives ~75% of its
      total runoff in the ablation period (i.e., from May to September). In addition,
      an early snowmelt is observed in accumulation season during study period,
      indicating the significant influence of natural and anthropogenic factors on high
      altitude areas.

PMID- 29464404
TI  - Assessing and enhancing the utility of low-cost activity and location sensors for
      exposure studies.
AB  - Nowadays, the advancement of mobile technology in conjunction with the
      introduction of the concept of exposome has provided new dynamics to the exposure
      studies. Since the addressing of health outcomes related to environmental
      stressors is crucial, the improvement of exposure assessment methodology is of
      paramount importance. Towards this aim, a pilot study was carried out in the two
      major cities of Greece (Athens, Thessaloniki), investigating the applicability of
      commercially available fitness monitors and the Moves App for tracking people's
      location and activities, as well as for predicting the type of the encountered
      location, using advanced modeling techniques. Within the frame of the study, 21
      individuals were using the Fitbit Flex activity tracker, a temperature logger,
      and the application Moves App on their smartphones. For the validation of the
      above equipment, participants were also carrying an Actigraph (activity sensor)
      and a GPS device. The data collected from Fitbit Flex, the temperature logger,
      and the GPS (speed) were used as input parameters in an Artificial Neural Network
      (ANN) model for predicting the type of location. Analysis of the data showed that
      the Moves App tends to underestimate the daily steps counts in comparison with
      Fitbit Flex and Actigraph, respectively, while Moves App predicted the movement
      trajectory of an individual with reasonable accuracy, compared to a dedicated
      GPS. Finally, the encountered location was successfully predicted by the ANN in
      most of the cases.

PMID- 29464405
TI  - The Role of Circulating Tumor DNA in Renal Cell Carcinoma.
AB  - OPINION STATEMENT: Next-generation sequencing (NGS) of circulating tumor DNA
      (ctDNA) is a novel technology that can complement tumor tissue NGS and has the
      potential to influence diagnosis and treatment of both localized and metastatic
      renal cell carcinoma (mRCC). ctDNA NGS is an attractive alternative to tumor
      tissue NGS because it circumvents the need for repeated, invasive tissue biopsies
      while providing a contemporary mutational profile of a patient's tumors. While
      the role of ctDNA NGS in non-small cell lung cancer and colorectal cancer is well
      established, studies of ctDNA NGS in mRCC are only hypothesis-generating to date.
      In the localized RCC setting, ctDNA has demonstrated potential as a surveillance
      biomarker for disease recurrence. Earlier detection of mRCC, prior to the onset
      of symptoms, may lead to improved clinical outcomes. NGS of ctDNA in mRCC is even
      more promising in patients with metastatic disease. The majority of patients with
      mRCC have detectable ctDNA. Thus, ctDNA could be used to select patients for
      biomarker-guided clinical trials, such as savolitinib in MET-positive papillary
      RCC. Furthermore, studies have shown that the mutational profile of mRCC in ctDNA
      evolves after treatment progression. The most exciting potential role for ctDNA
      in mRCC is as a predictive biomarker for response to immunotherapy. Studies have
      shown that tumor mutational burden (TMB) is predictive of response to immune
      checkpoint inhibitors, and hypermutated ctDNA can act as a surrogate biomarker
      for TMB and response to immunotherapy. While studies of ctDNA in RCC are still in
      their infancy, there are many promising roles for ctDNA in localized and
      metastatic RCC.

PMID- 29464407
TI  - Somatostatin and diabetic retinopathy: an evolving story.

PMID- 29464406
TI  - Acute exposure to copper induces variable intensity of oxidative stress in
      goldfish tissues.
AB  - Copper is an essential element, but at high concentrations, it is toxic for
      living organisms. The present study investigated the responses of goldfish,
      Carassius auratus, to 96 h exposure to 30, 300, or 700 MUg L-1 of copper II
      chloride (Cu2+). The content of protein carbonyls was higher in kidney (by 158%)
      after exposure to 700 mg L-1 copper, whereas in gills, liver, and brain, we
      observed lower content of protein carbonyls after exposure to copper compared
      with control values. Exposure to copper resulted in increased levels of lipid
      peroxides in gills (76%) and liver (95-110%) after exposure to 300 and 700 MUg L
      1 Cu2+. Low molecular mass thiols were depleted by 23-40% in liver and by 29-67%
      in kidney in response to copper treatment and can be used as biomarkers toxicity
      of copper. The activities of primary antioxidant enzymes, superoxide dismutase
      and catalase, were increased in liver as a result of Cu2+ exposure, whereas in
      kidney catalase activity was decreased. The activities of glutathione-related
      enzymes, glutathione peroxidase, glutathione-S-transferase, and glutathione
      reductase were decreased as a result of copper exposure, but glutathione
      reductase activity increased by 25-40% in liver. Taken together, these data show
      that exposure of fish to Cu2+ ions results in the development of low/high
      intensity oxidative stress reflected in enhanced activities of antioxidant and
      associated enzymes in different goldfish tissues.

PMID- 29464408
TI  - Isolation and identification of bovine nasopharyngeal mucosal epithelial cells
      and establishment of cell models of acute infection by foot-and-mouth disease
      virus.
AB  - Foot-and-mouth disease (FMD) commonly occurs via the respiratory tract, and
      bovine nasopharyngeal mucosal epithelial cells are the primary infection cells in
      cattle. The aim of the present study was to isolate and culture epithelial cells
      from the bovine nasopharyngeal mucosa in vitro using a mechanical separation
      method. The cells were expanded, established in continuous cell culture, and used
      for immunofluorescence cytochemistry and establishment of infection models. We
      detected pan-cytokeratin markers of bovine nasopharyngeal mucosal epithelial
      cells by immunofluorescence. Bovine nasopharyngeal mucosal epithelial cells were
      then infected with foot-and-mouth disease virus (FMDV) serum type O. RT-PCR
      demonstrated the successful establishment of acute FMDV infection in the cell
      models. This infection model provides the basis for clarification of the
      interaction between FMDV and host bovine nasopharyngeal mucosal epithelial cells
      in vitro.

PMID- 29464410
TI  - Simulations of microscopic propulsion of soft elastic bodies.
AB  - Using simulations that realistically model both hydrodynamic and elastic
      behavior, we study the motion of a microscopic, driven elastic sphere immersed in
      water. We first confirm the "jittery" relaxation recently predicted theoretically
      for an externally driven elastic sphere. The sphere is then divided in two and
      each section is driven internally with the two sections 180 degrees  out of
      phase. With periodic and perfectly symmetric driving, the elastic sphere
      spontaneously breaks symmetry and can attain macroscopic average swimming
      velocities to the right or left, the direction depending only on the initial
      state. With asymmetric driving the elastic sphere swims in one direction and the
      maximum speed is obtained with a 1/3:2/3 split. At high drive frequencies close
      to elastic resonances of the sphere, the motion can be quite efficient. At low
      drive frequencies the propulsion speed becomes independent of the elastic
      constants of the sphere and less efficient, but still substantial. Inertia is
      found to be an important driver of the behavior despite the small size of the
      spheres. As we model the full three-dimensional elasticity and compressible
      hydrodynamics, our simulations give not just qualitative indications but
      quantitative predictions for the motion.

PMID- 29464409
TI  - Solid-State NMR Investigation of Drug-Excipient Interactions and Phase Behavior
      in Indomethacin-Eudragit E Amorphous Solid Dispersions.
AB  - PURPOSE: To investigate the nature of drug-excipient interactions between
      indomethacin (IMC) and methacrylate copolymer Eudragit(r) E (EE) in the amorphous
      state, and evaluate the effects on formulation and stability of these amorphous
      systems. METHODS: Amorphous solid dispersions containing IMC and EE were spray
      dried with drug loadings from 20% to 90%. PXRD was used to confirm the amorphous
      nature of the dispersions, and DSC was used to measure glass transition
      temperatures (Tg). 13C and 15N solid-state NMR was utilized to investigate
      changes in local structure and protonation state, while 1H T1 and T1rho
      relaxation measurements were used to probe miscibility and phase behavior of the
      dispersions. RESULTS: Tg values for IMC-EE solid dispersions showed significant
      positive deviations from predicted values in the drug loading range of 40-90%,
      indicating a relatively strong drug-excipient interaction. 15N solid-state NMR
      exhibited a change in protonation state of the EE basic amine, with two distinct
      populations for the EE amine at -360.7 ppm (unprotonated) and -344.4 ppm
      (protonated). Additionally, 1H relaxation measurements showed phase separation at
      high drug load, indicating an amorphous ionic complex and free IMC-rich phase.
      PXRD data showed all ASDs up to 90% drug load remained physically stable after 2
      years. CONCLUSIONS: 15N solid-state NMR experiments show a change in protonation
      state of EE, indicating that an ionic complex indeed forms between IMC and EE in
      amorphous solid dispersions. Phase behavior was determined to exhibit nanoscale
      phase separation at high drug load between the amorphous ionic complex and excess
      free IMC.

PMID- 29464411
TI  - Optimal Human Passive Vestibulo-Ocular Reflex Adaptation Does Not Rely on Passive
      Training.
AB  - The vestibulo-ocular reflex (VOR) is the main vision-stabilising system during
      rapid head movements in humans. A visual-vestibular mismatch stimulus can be used
      to train or adapt the VOR response because it induces a retinal image slip error
      signal that drives VOR motor learning. The training context has been shown to
      affect VOR adaptation. We sought to determine whether active (self-generated)
      versus passive (externally imposed) head rotation vestibular training would
      differentially affect adaptation and short-term retention of the active and
      passive VOR responses. Ten subjects were tested, each over six separate 1.5-h
      sessions. We compared active versus passive head impulse (transient, rapid head
      rotations with peak velocity ~ 150  degrees /s) VOR adaptation training lasting
      15 min with the VOR gain challenged to increment, starting at unity, by 0.1 every
      90 s towards one side only (this adapting side was randomised to be either left
      or right). The VOR response was tested/measured in darkness at 10-min intervals,
      20-min intervals, and two single 60-min interval sessions for 1 h post-training.
      The training was active or passive for the 10- and 20-min interval sessions, but
      only active for the two single 60-min interval sessions. The mean VOR response
      increase due to training was ~ 10 % towards the adapting side versus ~2 % towards
      the non-adapting side. There was no difference in VOR adaptation and retention
      between active and passive VOR training. The only factor to affect retention was
      exposure to a de-adaptation stimulus. These data suggest that active VOR
      adaptation training can be used to optimally adapt the passive VOR and that
      adaptation is completely retained over 1 h as long as there is no visual feedback
      signal driving de-adaptation.

PMID- 29464412
TI  - Speech Intelligibility Predicted from Neural Entrainment of the Speech Envelope.
AB  - Speech intelligibility is currently measured by scoring how well a person can
      identify a speech signal. The results of such behavioral measures reflect neural
      processing of the speech signal, but are also influenced by language processing,
      motivation, and memory. Very often, electrophysiological measures of hearing give
      insight in the neural processing of sound. However, in most methods, non-speech
      stimuli are used, making it hard to relate the results to behavioral measures of
      speech intelligibility. The use of natural running speech as a stimulus in
      electrophysiological measures of hearing is a paradigm shift which allows to
      bridge the gap between behavioral and electrophysiological measures. Here, by
      decoding the speech envelope from the electroencephalogram, and correlating it
      with the stimulus envelope, we demonstrate an electrophysiological measure of
      neural processing of running speech. We show that behaviorally measured speech
      intelligibility is strongly correlated with our electrophysiological measure. Our
      results pave the way towards an objective and automatic way of assessing neural
      processing of speech presented through auditory prostheses, reducing confounds
      such as attention and cognitive capabilities. We anticipate that our
      electrophysiological measure will allow better differential diagnosis of the
      auditory system, and will allow the development of closed-loop auditory
      prostheses that automatically adapt to individual users.

PMID- 29464413
TI  - Influence of the static field on a heavy body in a rotating drum with liquid.
AB  - The behaviour of a heavy cylindrical body in a rotating horizontal cylindrical
      cavity filled with viscous liquid is investigated experimentally. Several modes
      of the body behaviour depending on the rate of the cavity rotation, i.e., the
      ratio of the centrifugal force of inertia and the gravity, are detected. At a
      fast rotation rate, the body makes the solid-body rotation, remaining immobile
      relative to the cavity due to the action of the centrifugal force. In the absence
      of rotation, under the influence of gravity, the body occupies a position in the
      lower part of the cavity. At slow uniform rotation rate, the body is dragged by
      the cavity boundary and shifts to some angle relative to the initial position.
      With an increase in the rotation rate, the body is repulsed from the cavity
      boundary and occupies a suspended position, stationary in the laboratory frame,
      at a certain distance from it. In the suspension regime and the partial repulsion
      regime, which precedes it, the body performs auto-oscillations that resemble the
      precession. The flow structures near the suspended cylinder are studied using the
      PIV method.

PMID- 29464414
TI  - Metal-Free Half-Metallicity in B-Doped gh-C3N4 Systems.
AB  - Half-metallicity rising from the s/p electrons has been one of the hot topics in
      spintronics. Based on the first-principles of calculation, we explore the
      magnetic properties of the B-doped graphitic heptazine carbon nitride (gh-C3N4)
      system. Ferromagnetism is observed in the B-doped gh-C3N4 system. Interestingly,
      its ground state phase (BC1@gh-C3N4) presents a strong half-metal property.
      Furthermore, the half-metallicity in BC1@gh-C3N4 can sustain up to 5% compressive
      strain and 1.5% tensile strain. It will lose its half-metallicity, however, when
      the doping concentration is below 6.25%. Our results show that such a metal-free
      half-metallic system has promising spintronic applications.

PMID- 29464415
TI  - Inflammatory Biomarkers During Bacterial Acute Rhinosinusitis.
AB  - PURPOSE OF REVIEW: Diagnosis of bacterial acute rhinosinusitis is difficult.
      Several attempts have been made to clarify the diagnostic criteria. Inflammatory
      biomarkers are easily obtainable variables that could shed light on both the
      pathophysiology and diagnosis of bacterial acute rhinosinusitis. The purpose of
      this review article is to assess literature concerning the course of inflammatory
      biomarkers during acute rhinosinusitis and the use of inflammatory biomarkers in
      diagnosing bacterial acute rhinosinusitis. RECENT FINDINGS: We included C
      reactive protein, erythrocyte sedimentation rate, white blood cell counts,
      procalcitonin, and nasal nitric oxide in this review and found that especially
      elevated C-reactive protein and erythrocyte sedimentation rate are related to a
      higher probability of a bacterial cause of acute rhinosinusitis. Still, normal
      levels of these two biomarkers are quite common as well, or the levels can be
      heightened even during viral respiratory infection without suspicion of bacterial
      involvement. Elevated levels of C-reactive protein or erythrocyte sedimentation
      rate support diagnosis of bacterial acute rhinosinusitis, but due to a lack of
      sensitivity, they should not be used to screen patients for bacterial acute
      rhinosinusitis.

PMID- 29464416
TI  - Sliding friction and contact angle hysteresis of droplets on microhole-structured
      surfaces.
AB  - Microstructured surfaces with continuous solid topography have many potential
      applications in biology and industry. To understand the liquid transport property
      of microstructured surfaces with continuous solid topography, we studied the
      sliding behavior of a droplet on microhole-structured surfaces. We found that the
      sliding friction of the droplet increased with increasing solid area fraction due
      to enlarged apparent contact area and enhanced contact angle hysteresis. By
      introducing a correction factor to the modified Cassie-Baxter relation, we
      proposed an improved theoretical model to better predict the apparent receding
      contact angle. Our experimental data also revealed that the geometric topology of
      surface microstructures could affect the sliding friction with microhole
      decorated surfaces, exhibiting a larger resistance than that for micropillar
      decorated surfaces. Assisted by optical microscopy, we attributed this topology
      effect to the continuity and the true total length of the three-phase contact
      line at the receding edge during the sliding. Our study provides new insights
      into the liquid sliding behavior on microstructured surfaces with different
      topologies, which may help better design functional surfaces with special liquid
      transport properties.

PMID- 29464417
TI  - Stability of a stationary plane-parallel flow of a ternary fluid between two
      vertical plates maintained at constant different temperatures.
AB  - The linear stability of a steady convective flow of a ternary mixture placed
      between differently heated vertical rigid plates is studied. The applied
      temperature gradient induces concentration gradients due to the Soret effect. The
      analysis is done for the case when separation ratios of ternary mixture, i.e.,
      Soret coefficients, have different signs but the net separation ratio is
      negative. The stability maps in terms of the Grashof number and net separation
      ratio are obtained and discussed for monotonic and oscillatory modes of
      instability. The previous results for long-wave instability of a binary mixture
      were recovered in the limit when one of the Soret coefficients tends to zero. For
      finite-wavelength perturbations the previous results were extended by discovering
      the oscillatory instability.

PMID- 29464418
TI  - Annual costs attributed to atrial fibrillation management: cross-sectional study
      of primary healthcare electronic records.
AB  - Atrial fibrillation (AF) is the most common chronic arrhythmia, with increasing
      healthcare and economic burden and a prevalence which increases with progressive
      ageing. This study aims to describe overall annual costs per patient for
      management of non-valvular AF in a primary healthcare (PHC) setting and compare
      these costs between the groups of patients treated with vitamin K antagonists,
      antiplatelets or non-treated through a population-based study conducted with
      electronic health records. We analysed annual costs per person of 19,787 patients
      in 2012; PHC visits, hospital admissions, AF-related events requiring hospital
      admission, referrals to secondary specialists, sick leave, diagnostic tests and
      laboratory tests at PHC level, including INR determinations performed in PHC, and
      drug therapy. Higher costs of AF management were associated with increasing age,
      male sex, stroke and bleeding risks, comorbidities and occurrence of events
      associated to AF. The sensitivity analyses conducted showed that PHC visits and
      hospitalizations represented the most important part of overall costs for all
      patients.

PMID- 29464419
TI  - Light-Induced Covalent Buffer Adducts to Histidine in a Model Protein.
AB  - PURPOSE: Light is known to induce histidine (His) oxidation and His-His
      crosslinking in proteins. The crosslinking is resulted from the nucleophilic
      attack of a His to a photooxidized His from another protein. The goal of this
      work is to understand if covalent buffer adducts on His residues can be generated
      by light through similar mechanisms in nucleophilic buffers such as Tris and His.
      METHODS: A model protein (DNase) was buffer exchanged into nucleophilic buffers
      before light exposure. Photogenerated products were characterized by tryptic
      peptide mapping with mass spectrometry (MS) analysis. Several buffer adductions
      on His residues were identified after light exposure. To understand the
      influencing factors of such reactions, the levels of adducts were measured for
      six nucleophilic buffers on all His residues in DNase. RESULTS: The levels of
      adducts were found to correlate with the solvent accessibility of the His
      residue. The levels of adducts also correlate with the structure of the
      nucleophile, especially the steric restrictions of the nucleophile. The levels of
      adducts can be higher than that of other His photoreaction products, including
      photooxidation and crosslinking. CONCLUSIONS: In nucleophilic buffers, light can
      induce covalently-linked adducts to His residues.

PMID- 29464420
TI  - Dexmedetomidine versus propofol-opioid for sedation in transcatheter aortic valve
      implantation patients: a retrospective analysis of periprocedural gas exchange
      and hemodynamic support.
AB  - PURPOSE: Different sedation regimens have been described for use during
      transfemoral transcatheter aortic valve implantation (tf-TAVI) for treatment in
      patients with severe aortic stenosis. The purpose of this study was to compare
      dexmedetomidine (DEX) with a combination of propofol-opioid (PO) with respect to
      periprocedural gas exchange and hemodynamic support. METHODS: Data from a cohort
      of patients sedated with either DEX or PO for tf-TAVI were retrospectively
      analyzed from a prospectively maintained TAVI registry. Operative risk was
      determined from comorbidities and risk scores. Periprocedural partial pressure of
      carbon dioxide (PaCO2) was chosen as the primary endpoint. Other differences in
      gas exchange, need for catecholamine therapy, the frequency of conversion to
      general anesthesia, and need for sedative "rescue therapy" (in DEX patients) were
      secondary endpoints. Inverse probability of treatment weighting (IPTW) was used
      for analysis to minimize any selection bias. RESULTS: Of the 297 patients (140
      PO, 157 DEX) included, the median [interquartile range] periprocedural PaCO2
      values of DEX patients were significantly lower than in PO patients (40 [36-45]
      mmHg vs 44 [40-49] mmHg, respectively; median difference -4 mmHg; 95% confidence
      interval, -5 to -3 mmHg; P < 0.001). Hypercapnia (PaCO2 > 45 mmHg) was
      significantly less frequent in DEX patients compared with the PO group (25% vs
      42%, respectively; P = 0.005). Vasopressor support was more frequent in the PO
      group compared with DEX (68% vs 25%, respectively; P < 0.001). Conversion to
      general anesthesia was not different between groups (9%, PO vs 3%, DEX; P =
      0.051). Additional sedatives/opioids were required in 25 (16%) of the DEX
      patients. CONCLUSIONS: In sedated TAVI patients, DEX was associated with lower
      PaCO2 values and reduced requirements for vasopressor support, making it a
      promising alternative to PO for sedation during TAVI. TRIAL REGISTRATION:
      www.ClinicalTrials.gov (NCT01390675). Registered 11 July 2011.

PMID- 29464421
TI  - Two inhibitors of yeast plasma membrane ATPase 1 (ScPma1p): toward the
      development of novel antifungal therapies.
AB  - Given that many antifungal medications are susceptible to evolved resistance,
      there is a need for novel drugs with unique mechanisms of action. Inhibiting the
      essential proton pump Pma1p, a P-type ATPase, is a potentially effective
      therapeutic approach that is orthogonal to existing treatments. We identify
      NSC11668 and hitachimycin as structurally distinct antifungals that inhibit yeast
      ScPma1p. These compounds provide new opportunities for drug discovery aimed at
      this important target.

PMID- 29464422
TI  - Relationship between carotid artery atherosclerosis and bulb geometry.
AB  - The carotid bifurcation is a common site of atherosclerotic plaque. Plaque
      development is thought to occur preferentially at geometrically predisposed areas
      such as arterial branch points. The aim of this study was to investigate the
      geometric and anatomical variables that contribute to the development of carotid
      plaque using three-dimensional (3D) ultrasound. Sixty-seven consecutive
      outpatients referred for elective coronary angiography underwent 3D carotid
      ultrasound scans for the purpose of carotid plaque quantification. Geometric
      quantification of the left and right carotid bulbs were performed retrospectively
      on this study population. Geometric values such as angle, area and length of the
      carotid bulb and the bifurcation were determined using QLAB software (Philips
      Healthcare). Plaque volume within the carotid bulb and artery branches was
      quantified using the stacked contour method. Pearson's correlation and linear
      regression analysis were used to determine the relationship between anatomical
      variables and plaque volume. The mean age for the total patient population was
      65.9 +/- 11.5 years. Carotid bulb inflow area (BIA) (r = 0.28, p = 0.001), bulb
      volume (BV) (r = 0.21, p = 0.01) and bifurcation angle (BifA) (r = 0.18, p =
      0.04) showed a positive linear relationship with plaque volume. In contrast,
      internal carotid artery angle (ICAA) (r = - 0.18, p = 0.04) and bulb flare (r = -
      0.20, p = 0.02) displayed a negative linear relationship with plaque volume. When
      adjusting for age and sex, only the BIA remained significant (beta = 0.18, p =
      0.04). Geometric variables were identified as potential risk factors associated
      with plaque volume in the carotid bulb. Further analysis of the evolution of the
      BIA as well as the relationship to other geometric variables could create a
      stronger predictive model of atherosclerosis as well as assist in preoperative
      planning.

PMID- 29464423
TI  - Selenylation modification: enhancement of the antioxidant activity of a
      Glycyrrhiza uralensis polysaccharide.
AB  - Selenium (Se) is an essential trace element for human beings and many other forms
      of life. Organic selenium from natural foods has greater bioavailability and is
      safer than inorganic selenium species. In this article, the structural properties
      and antioxidant activities of a Glycyrrhiza uralensis polysaccharide (GUP) after
      selenylation modification were investigated. The GUP was extracted by water
      decoction and ethanol precipitation and purified via protein elimination using
      the trichloroacetic acid method and column chromatography. The purified product
      was subsequently modified by the nitric acid-sodium selenite (HNO3-Na2SeO3)
      method. The selenized GUP (SeGUP) product was characterized by Fourier transform
      infrared (FT-IR) spectroscopy, and its thermal stability, particle size, and
      antioxidant activities were investigated. FT-IR analysis indicated that the
      selenium in SeGUP existed mainly as O-Se-O. The thermal stability and particle
      size of SeGUP differed significantly from those of GUP. Moreover, compared to
      GUP, SeGUP exhibited greater antioxidant activities in vitro and in vivo. These
      results indicate that selenylation modification significantly enhances the
      antioxidant activity of SeGUP, increasing its potential for application as an
      antioxidant. Graphical abstract ?.

PMID- 29464424
TI  - Prevalence and risk factors for CTX-M gram-negative bacteria in hospitalized
      patients at a tertiary care hospital in Kilimanjaro, Tanzania.
AB  - Emergence and spread of extended spectrum beta-lactamase (ESBL)-producing gram
      negative bacteria, mainly due to CTX-M, is a major global public health problem.
      Patients infected with ESBL-producing gram-negative bacteria have an increased
      risk of treatment failure and death. We investigated the prevalence and risk
      factors for CTX-M gram-negative bacteria isolated from clinical specimens of
      patients hospitalized at a tertiary care hospital in Kilimanjaro, Tanzania.
      Isolated gram-negative bacteria from inpatients admitted at Kilimanjaro Christian
      Medical Centre (KCMC) between August 2013 and August 2015 were fully genome
      sequenced. The prevalence of ESBL-producing gram-negative bacteria was determined
      based on the presence of blaCTX-M. The odds ratio (OR) and risk factors for ESBL
      producing gram-negative bacteria due to CTX-M were assessed using logistic
      regression models. The overall CTX-M prevalence (95% CI) was 13.6% (10.1-18.1).
      Adjusted for other factors, the OR of CTX-M gram-negative bacteria for patients
      previously hospitalized was 0.26 (0.08-0.88), p = 0.031; the OR for patients
      currently on antibiotics was 4.02 (1.29-12.58), p = 0.017; the OR for patients
      currently on ceftriaxone was 0.14 (0.04-0.46), p = 0.001; and the OR for patients
      with wound infections was 0.24 (0.09-0.61), p = 0.003. The prevalence of ESBL
      producing gram-negative bacteria due to CTX-M in this setting is relatively low
      compared to other previous reports in similar settings. However, to properly stop
      further spread in the hospital, we recommend setting up a hospital surveillance
      system that takes full advantage of the available next-generation sequencing
      facility to routinely screen for all types of bacterial resistance genes.

PMID- 29464425
TI  - The Interaction Between Child Behavioral Inhibition and Parenting Behaviors:
      Effects on Internalizing and Externalizing Symptomology.
AB  - Both child temperament and parenting have been extensively researched as
      predictors of child outcomes. However, theoretical models suggest that specific
      combinations of temperament styles and parenting behaviors are better predictors
      of certain child outcomes such as internalizing and externalizing symptoms than
      either temperament or parenting alone. The current qualitative review examines
      the interaction between one childhood temperamental characteristic (child
      behavioral inhibition) and parenting behaviors, and their subsequent impact on
      child psychopathology. Specifically, the moderating role of parenting on the
      relationship between child behavioral inhibition and both internalizing and
      externalizing psychopathology is examined, and the methodological variations
      which may contribute to inconsistent findings are explored. Additionally, support
      for the bidirectional relations between behavioral inhibition and parenting
      behaviors, as well as for the moderating role of temperament on the relationships
      between parenting and child outcomes, is briefly discussed. Finally, the clinical
      applicability of this overall conceptual model, specifically in regard to future
      research directions and potential clinical interventions, is considered.

PMID- 29464426
TI  - The impact of historical breastfeeding practices on the incidence of cancer in
      France in 2015.
AB  - PURPOSE: The purpose of the study was to estimate the number of new breast cancer
      cases in France in 2015 attributable to breastfeeding for durations below
      recommendations (at least 6 months per child), and cases prevented through
      historical breastfeeding. As a secondary analysis, the corresponding numbers for
      ovarian cancer were estimated. METHODS: Historical breastfeeding data were
      obtained from population surveys. Duration of breastfeeding data were obtained
      from the French Epifane cohort study. Relative risks were obtained from meta
      analyses, cohort, and case-control studies. Cancer incidence data were obtained
      from the French Network of Cancer Registries. A 10-year latency period was
      assumed. RESULTS: Among parous women 25 years of age and older, 14.1% breastfed
      for at least 6 months per child born before 2006. As a result, 1,712 new breast
      cancer cases (3.2% of all new breast cancer cases) were attributable to
      breastfeeding for < 6 months per child, while actual breastfeeding practices
      prevented 765 breast cancer cases. Furthermore, 411 new ovarian cancer cases
      (8.6% of all new ovarian cancer cases) may be attributable to breastfeeding for <
      6 months per child, with breastfeeding preventing 163 ovarian cancer cases.
      CONCLUSIONS: The historically low breastfeeding prevalence and duration in France
      led to numerous avoidable cancer cases.

PMID- 29464427
TI  - Minority Stressors Associated with Sexual Risk Behaviors and HIV Testing in a
      U.S. Sample of Transgender Individuals.
AB  - The majority of published research on transgender health focuses on associations
      between external minority stressors (e.g., discrimination) and health. Little is
      known about how internal minority stressors (e.g., identity concealment and
      expecting rejection) might predict HIV disparities. The current study addresses
      this gap by examining the association between external and internal minority
      stressors and sexual risk behaviors and HIV testing history in a sample of 300
      transgender adults across the U.S. Transgender-related discrimination and
      expecting rejection were associated with sexual risk behaviors. When controlling
      for covariates, none of the minority stressors were associated with HIV testing.
      Results illustrate how minority stress, both external and internal, may operate
      uniquely for transgender individuals.

PMID- 29464428
TI  - Changes in Providers' Self-Efficacy and Intentions to Provide Safer Conception
      Counseling Over 24 Months.
AB  - High rates of fertility desires, childbearing and serodiscordant partnerships
      among people living with HIV (PLHIV) in Uganda underscore the need to promote use
      of safer conception methods (SCM). Effective SCM exist but few PLHIV benefit from
      provider-led safer conception counseling (SCC) and comprehensive national SCC
      guidelines are still lacking. Providers' self-efficacy, intentions and attitudes
      for SCC impact provision and should inform development of services, but there are
      no longitudinal studies that assess these important constructs. This study
      reports on changes in providers' knowledge, attitudes, motivation and confidence
      to provide SCC among a 24-month observational cohort of Ugandan HIV providers.
      Compared to baseline, providers evidenced increased awareness of SCM, perceived
      greater value in providing SCC, saw all SCM but sperm washing as likely to be
      acceptable to clients, reported consistently high interest in and peer support
      for providing SCC, and perceived fewer barriers at the 24-month follow-up.
      Providers' intentions for providing SCC stayed consistently high for all SCM
      except manual self-insemination which decreased at 24 months. Self-efficacy for
      providing SCC increased from baseline with the greatest improvement in providers'
      confidence in advising serodiscordant couples where the man is HIV-infected.
      Providers consistently cite the lack of established guidelines, training, and
      their own reluctance to broach the issue with clients as significant barriers to
      providing SCC. Despite providers being more interested and open to providing SCC
      than ever, integration of SCC into standard HIV services has not happened.
      Concerted efforts are needed to address remaining barriers by establishing
      national SCC guidelines and implementing quality provider training.

PMID- 29464429
TI  - A Conceptual Model of Dyadic Coordination in HIV Care Engagement Among Couples of
      Black Men Who Have Sex with Men: A Qualitative Dyadic Analysis.
AB  - Among Black men who have sex with men (MSM), HIV incidence is disproportionately
      high and HIV care engagement is disproportionately low. There may be important
      opportunities to leverage the primary relationship to improve engagement in HIV
      care and treatment among Black MSM couples. Using dyadic qualitative analysis of
      semi-structured, one-on-one interviews, we explored dyadic aspects of HIV care
      engagement among 14 Black MSM couples in which at least one partner was HIV
      positive and identified as a Black cisgender man. Findings showed that men varied
      in how involved they were in their HIV-positive partner's care and treatment, and
      in how they reciprocated their partner's involvement. Patterns of dyadic HIV care
      engagement supported a conceptual model of dyadic coordination that describes
      Black MSM relationships in terms of two conceptual dimensions of dyadic HIV care
      engagement, and guides future intervention designs with Black MSM couples.

PMID- 29464431
TI  - A SEPSECS mutation in a 23-year-old woman with microcephaly and progressive
      cerebellar ataxia.
AB  - Mutations in the SEPSECS gene are associated with pontocerebellar hypoplasia type
      2D. Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare autosomal
      recessive neurodegenerative disorders, mainly affecting pons and cerebellum.
      Patients have severe motor and cognitive impairments and often die during
      infancy. Here, we report a 23-year-old woman with slowly progressive cerebellar
      ataxia and cognitive impairment, in whom a homozygous missense mutation in the
      SEPSECS gene (c.1321G>A; p.Gly441Arg) was identified with whole exome sequencing.
      Our findings underline that defects in selenoprotein synthesis can also result in
      milder cerebellar atrophy presenting at a later age.

PMID- 29464430
TI  - HIV Testing and Counseling Among Female Sex Workers: A Systematic Literature
      Review.
AB  - HIV testing uptake continues to be low among Female Sex Workers (FSWs). We
      synthesizes evidence on barriers and facilitators to HIV testing among FSW as
      well as frequencies of testing, willingness to test, and return rates to collect
      results. We systematically searched the MEDLINE/PubMed, EMBASE, SCOPUS databases
      for articles published in English between January 2000 and November 2017. Out of
      5036 references screened, we retained 36 papers. The two barriers to HIV testing
      most commonly reported were financial and time costs-including low income,
      transportation costs, time constraints, and formal/informal payments-as well as
      the stigma and discrimination ascribed to HIV positive people and sex workers.
      Social support facilitated testing with consistently higher uptake amongst
      married FSWs and women who were encouraged to test by peers and managers. The
      consistent finding that social support facilitated HIV testing calls for its
      inclusion into current HIV testing strategies addressed at FSW.

PMID- 29464432
TI  - Sharpness-Aware Low-Dose CT Denoising Using Conditional Generative Adversarial
      Network.
AB  - Low-dose computed tomography (LDCT) has offered tremendous benefits in radiation
      restricted applications, but the quantum noise as resulted by the insufficient
      number of photons could potentially harm the diagnostic performance. Current
      image-based denoising methods tend to produce a blur effect on the final
      reconstructed results especially in high noise levels. In this paper, a deep
      learning-based approach was proposed to mitigate this problem. An adversarially
      trained network and a sharpness detection network were trained to guide the
      training process. Experiments on both simulated and real dataset show that the
      results of the proposed method have very small resolution loss and achieves
      better performance relative to state-of-the-art methods both quantitatively and
      visually.

PMID- 29464433
TI  - Optimizing Travel Time to Outpatient Interventional Radiology Procedures in a
      Multi-Site Hospital System Using a Google Maps Application.
AB  - The purpose of this study is to determine whether a custom Google Maps
      application can optimize site selection when scheduling outpatient interventional
      radiology (IR) procedures within a multi-site hospital system. The Google Maps
      for Business Application Programming Interface (API) was used to develop an
      internal web application that uses real-time traffic data to determine estimated
      travel time (ETT; minutes) and estimated travel distance (ETD; miles) from a
      patient's home to each a nearby IR facility in our hospital system. Hypothetical
      patient home addresses based on the 33 cities comprising our institution's
      catchment area were used to determine the optimal IR site for hypothetical
      patients traveling from each city based on real-time traffic conditions. For
      10/33 (30%) cities, there was discordance between the optimal IR site based on
      ETT and the optimal IR site based on ETD at non-rush hour time or rush hour time.
      By choosing to travel to an IR site based on ETT rather than ETD, patients from
      discordant cities were predicted to save an average of 7.29 min during non-rush
      hour (p = 0.03), and 28.80 min during rush hour (p < 0.001). Using a custom
      Google Maps application to schedule outpatients for IR procedures can effectively
      reduce patient travel time when more than one location providing IR procedures is
      available within the same hospital system.

PMID- 29464434
TI  - Vibrational spectra of DNA in the confined interglobular volume of photonic
      crystal.
AB  - The impact of confinement of DNA molecules in a limited volume of the cavity of
      photonic crystals (PC) on the vibrational properties of the DNA molecule and its
      conformation is studied. According to our preliminary study, the aqueous shell is
      removed when the DNA molecules are infiltrated into the PC cavities. Raman
      scattering (RS) DNA marker lines showed a dramatic conformational change of DNA
      in the PC cavities and the appearance of new unknown conformational states. We
      observed the enhancement of vibrational modes of DNA in the PC in comparison with
      free DNA of about tenfold and the absence of vibrational modes in DNA bases in a
      region of 1450-1700 cm-1. The observed features in the RS spectra of DNA are
      explained by the impact of confined interglobular volume and strong localization
      of the electromagnetic field. Namely, FDTD simulations in linear regime
      demonstrate the localization of light in cavities of PC with an approximately
      ninefold enhancement of the electric field within the photonic stop-band, which
      is the main reason for RS amplification.

PMID- 29464435
TI  - Palliative Care for Movement Disorders.
AB  - PURPOSE OF REVIEW: While care for patients with movement disorders has
      traditionally focused on motor symptoms, there is increasing evidence that
      optimal care for these disorders is more complex both in terms of the spectrum of
      symptoms experienced by patients (e.g., pain, depression) and the
      multidimensional needs of patients and their families. Palliative care is an
      approach to the care of patients and families affected by serious illnesses that
      seeks to relieve suffering by addressing complex medical symptoms, psychosocial
      issues, spiritual well-being, and goals of care. While traditionally associated
      with cancer and hospice, more recent work in palliative care has focused on
      integrating a palliative care approach from the time of diagnosis for patients
      with chronic illnesses, including movement disorders. RECENT FINDINGS: Studies of
      patients with movement disorders and their family caregivers suggest that these
      patients have significant unmet needs under current models of care, including
      underrecognition and treatment of non-motor symptoms, inadequate psychosocial
      support, and suboptimal end-of-life care. We describe how a palliative care
      approach can empower clinicians, patients, and families to reduce common sources
      of suffering and optimize quality of life. This field recognizes the importance
      of primary palliative care (palliative skills useful for any clinician caring for
      persons caring for serious illness) as a foundation of the palliative care
      approach and complementary to specialist palliative care. In this article, we
      will focus on primary palliative care skills for movement disorder specialists
      including providing a diagnosis and prognosis with compassion, discussing goals
      of care, complex symptom management, caregiver support, spiritual and emotional
      well-being, and referral to hospice and specialist palliative care. A palliative
      care approach complements other efforts in movement disorder care. Research is
      needed to evaluate and develop therapeutic interventions and models of care
      applying a palliative care approach.

PMID- 29464436
TI  - The effect of pH on the dynamics of natural membranes.
AB  - Pure phospholipids and membrane fragments from bacterial cells living under
      various conditions were studied against the influence of the surrounding acidity
      on the internal dynamics. For that we compared mean square displacements
      extracted from elastic incoherent neutron scattering data, measured both at low
      and at neutral pH, of the phospholipids 1,2-dimyristoyl-sn-glycero-3
      phosphocholine and of samples from neutralophilic and acidophilic micro-organisms
      (some being hyperthermophilic and others mesophilic). The lipids showed a slight
      shift in the phase transition temperature of about 4 degrees under pH variation
      and became slightly more mobile at lower pH. The membrane fragments not used to
      extreme acidic conditions were significantly more sensitive to variations in the
      pH values, whereas the acidophilic and -tolerant samples were much less
      influenced by this parameter. They presented the higher softness at low pH, which
      was closer to their native condition. Such findings might be a hint for
      adaptation mechanisms to different acidity conditions.

PMID- 29464438
TI  - Tregs in SLE: an Update.
AB  - PURPOSE OF REVIEW: There has been great interest in understanding why T
      regulatory cells (Tregs) are reduced in number and/or in function in several
      autoimmune diseases including systemic lupus erythematosus (SLE). Although
      research has provided some answers, there is still much to learn. RECENT
      FINDINGS: Recent investigations on the mechanisms responsible for the impairment
      of the Tregs in SLE have identified relevant abnormalities in cellular and
      molecular pathways that have been instrumental in the design of studies in animal
      models and in the development of pilot immunotherapeutic studies in lupus
      patients. We review the progress made in the field in the last 5 years,
      discussing the mechanistic studies, together with the preclinical and clinical
      works that are moving forward the understanding of the physiopathology of Tregs
      in SLE.

PMID- 29464437
TI  - Cutaneous Manifestations of Reactions to Biologics.
AB  - PURPOSE OF REVIEW: The goal of this paper is to review the major adverse
      cutaneous reactions that have been reported to the most commonly used biologics.
      RECENT FINDINGS: Anti-TNF agents and immune checkpoint inhibitors have
      significant, immune-mediated cutaneous manifestations that can necessitate
      discontinuation. Anti-TNF agents, IL-6 inhibitors, and IL-12/23 inhibitors can
      paradoxically cause psoriasis flares or unmask previously undiagnosed psoriasis.
      IL-17 inhibitors are unique in increasing risk for Candida infections. Benign
      injection site reactions, non-specific rash, cellulitis, and hypersensitivity
      reactions are relatively common adverse events. A wide variety of cutaneous
      reactions caused by biologics have been reported, ranging from benign injection
      site reactions to life-threatening cutaneous reactions necessitating
      discontinuation of the implicated biologic agent.

PMID- 29464441
TI  - Left heart pressures can be the key to know the limitation of left ventricular
      assist device support against progression of aortic insufficiency.
AB  - Aortic insufficiency (AI) is a worrisome complication under left ventricular
      assist device (LVAD) support. AI progression causes LVAD-left ventricular (LV)
      recirculation and can require surgical intervention to the aortic valve. However,
      the limitations of LVAD support are not well known. Using an animal model of LVAD
      with AI, the effect of AI progression on hemodynamics and myocardial oxygen
      metabolism were investigated. Five goats (Saanen 48 +/- 2 kg) underwent
      centrifugal type LVAD, EVAHEART, implantation. The AI model was established by
      placing a vena cava filter in the aortic valve. Cardiac dysfunction was induced
      by continuous beta-blockade (esmolol) infusion. Hemodynamic values and myocardial
      oxygen extraction ratio (O2ER) were evaluated while changing the degree of AI
      which was expressed as the flow rate of LVAD-LV recirculation (recirculation
      rate). Diastolic aortic pressure was decreased with AI progression and correlated
      negatively with the recirculation rate (p = 0.00055). Systolic left ventricular
      pressure (LVP) and mean left atrial pressure (LAP) were increased with AI
      progression and correlated positively with the recirculation rate (p = 0.010,
      0.023, respectively). LVP and LAP showed marked exponential increases when the
      recirculation rate surpassed 40%. O2ER was also increased with AI progression and
      had a significant positive correlation with the recirculation rate (p =
      0.000043). O2ER was increased linearly, with no exponential increase. AI
      progression made it difficult to reduce the cardiac pressure load, worsening
      myocardial oxygen metabolism. The exponential increase of left heart pressures
      could be the key to know the limitation of LVAD support against AI progression.

PMID- 29464442
TI  - The use of VV-ECMO in patients with drug dependencies.
AB  - The purpose of this study is to determine the effect of illicit drug and alcohol
      dependencies on mortality, length of stay, and complications in patients who have
      been supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO)
      following respiratory failure not responsive to conventional methods of
      ventilation. 584 VV-ECMO referrals received at Wythenshawe Hospital were reviewed
      for evidence of drug dependency. 13 patients were identified as being drug
      dependent and having undergone treatment with VV-ECMO. A matched cohort of 13 non
      drug-dependent patients was identified using date of birth, pre-ECMO Murray
      Score, and primary diagnosis. The outcomes were compared. 19 more complications
      were found amongst the drug-dependent patients compared with the non-drug
      dependent cohort (39 vs 20). A mean difference of 1.46 complications per patient
      was calculated (p = 0.005). Mortality after 180 days was reported in 4 of the
      drug-dependent patients, compared with one in the matched cohort. Length of stay
      on ECMO was increased on average by 1.93 days amongst the drug-dependent patients
      (p = 0.557); however, the sample size was not great enough to achieve statistical
      significance. Patients with drug dependencies undergoing VV-ECMO have more
      complications when compared with a cohort of patients with no proven or suspected
      drug dependencies. Differences in morbidity and mortality were not statistically
      significant.

PMID- 29464443
TI  - A visual familiarity account of evidence for orthographic processing in pigeons
      (Columbia livia): a reply to Scarf, Corballis, Gunturkun, and Colombo (2017).
AB  - Scarf et al. (Proc Natl Acad Sci 113(40):11272-11276, 2016) demonstrated that
      pigeons, as with baboons (Grainger et al. in Science 336(6078):245-248, 2012;
      Ziegler in Psychol Sci. https://doi.org/10.1177/0956797612474322 , 2013), can be
      trained to display several behavioural hallmarks of human orthographic
      processing. But, Vokey and Jamieson (Psychol Sci 25(4):991-996, 2014)
      demonstrated that a standard, autoassociative neural network model of memory
      applied to pixel maps of the words and nonwords reproduces all of those results.
      In a subsequent report, Scarf et al. (Anim Cognit 20(5):999-1002, 2017)
      demonstrated that pigeons can reproduce one more marker of human orthographic
      processing: the ability to discriminate visually presented four-letter words from
      their mirror-reversed counterparts (e.g. "LEFT" vs. " "). The current report
      shows that the model of Vokey and Jamieson (2014) reproduces the results of Scarf
      et al. (2017) and reinforces the original argument: the recent results thought to
      support a conclusion of orthographic processing in pigeons and baboons are
      consistent with but do not force that conclusion.

PMID- 29464444
TI  - Cuprizone Administration Alters the Iron Metabolism in the Mouse Model of
      Multiple Sclerosis.
AB  - Cuprizone (CZ) is a widely used copper chelating agent to develop non-autoimmune
      animal model of multiple sclerosis, characterized by demyelination of the corpus
      callosum (CC) and other brain regions. The exact mechanisms of CZ action are
      still arguable, but it seems that the only affected cells are the mature
      oligodendrocytes, possibly via metabolic disturbances caused by copper
      deficiency. During the pathogenesis of multiple sclerosis, high amount of
      deposited iron can be found throughout the demyelinated areas of the brain in the
      form of extracellular iron deposits and intracellularly accumulated iron in
      microglia. In the present study, we used the accepted experimental model of 0.2%
      CZ-containing diet with standard iron concentration to induce demyelination in
      the brain of C57BL/6 mice. Our aim was to examine the changes of iron homeostasis
      in the CC and as a part of the systemic iron regulation, in the liver. Our data
      showed that CZ treatment changed the iron metabolism of both tissues; however, it
      had more impact on the liver. Besides the alterations in the expressions of iron
      storage and import proteins, we detected reduced serum iron concentration and
      iron stores in the liver, together with elevated hepcidin levels and feasible
      disturbances in the Fe-S cluster biosynthesis. Our results revealed that the CZ
      containing diet influences the systemic iron metabolism in mice, particularly the
      iron homeostasis of the liver. This inadequate systemic iron regulation may
      affect the iron homeostasis of the brain, eventually indicating a relationship
      among CZ treatment, iron metabolism, and neurodegeneration.

PMID- 29464445
TI  - Night shift work and breast cancer: a pooled analysis of population-based case
      control studies with complete work history.
AB  - Night shift work has been suspected to increase breast cancer risk but
      epidemiological studies have been inconsistent due to heterogeneous assessment of
      exposure to night work. To overcome this limitation, we pooled data of five
      population-based case-control studies from Australia, Canada, France, Germany,
      and Spain into a single harmonized dataset using a common definition of night
      work including 6093 breast cancer cases and 6933 population controls. The odds
      ratio for breast cancer in women who ever worked at night for at least 3 h
      between midnight and 5 a.m. as compared to never night workers was 1.12 (95% CI
      1.00-1.25). Among pre-menopausal women, this odds ratio was 1.26 [1.06-1.51],
      increasing to 1.36 [1.07-1.74] for night shifts >= 10 h, 1.80 [1.20-2.71] for
      work >= 3 nights/week, and 2.55 [1.03-6.30] for both duration of night work >= 10
      years and exposure intensity >= 3 nights/week. Breast cancer risk in pre
      menopausal women was higher in current or recent night workers (OR = 1.41 [1.06
      1.88]) than in those who had stopped night work more than 2 years ago. Breast
      cancer in post-menopausal women was not associated with night work whatever the
      exposure metric. The increase in risk was restricted to ER+ tumors, particularly
      those who were both ER+ and HER2+ . These results support the hypothesis that
      night shift work increases the risk of breast cancer in pre-menopausal women,
      particularly those with high intensity and long duration of exposure. Risk
      difference between pre- and post-menopausal women deserves further scrutiny.

PMID- 29464446
TI  - Supportive therapy in gastroenteropancreatic neuroendocrine tumors: Often
      forgotten but important.
AB  - Neuroendocrine tumors (NETs) are a group of rare and heterogeneous malignancies
      that can develop in various organs. A significant number of
      gastroenteropancreatic neuroendocrine tumours (GEP-NETs) is functionally active
      and presents with symptoms related to the secretion of biologically active
      substances, leading to the development of distinct clinical syndromes. There are
      various therapeutic approaches for GEP-NETs, including curative surgery,
      palliative surgery, local-ablative and loco-regional therapies as well as
      systemic therapeutic options including peptide receptor radionuclide therapy,
      cytotoxic therapy, and molecularly targeted therapies. Specific supportive
      therapy of patients with NETs includes management or prevention of hormone
      related clinical syndromes and paraneoplastic states. Supportive therapy plays a
      key role in NET treatment. Supportive therapy includes debulking surgery and
      interventional radiologic techniques to reduce tumour bulk or load, as well as
      systemic medical treatment options to manage or prevent hypersecretion syndromes
      and treatment-related side effects. Supportive therapies are a type of of
      comprehensive treatment addressing the patient as a whole person throughout the
      process of NET treatment. Therefore, supportive therapy also encompasses
      psychosocial support, expert nursing, nutritional support and management of
      cancer related pain.

PMID- 29464447
TI  - Pathogenesis of Skin Injury of Systemic Lupus Erythematosus.
AB  - PURPOSE OF REVIEW: The second most common clinical expression in lupus patients
      is skin damage that the pathogenesis remains unclear. We discuss the role of
      pathological factors in the development of skin damage in SLE. RECENT FINDINGS:
      Skin deposited IgG is a crucial pathologic factor in the development of skin
      damage in SLE. Macrophages and signaling of TNFalpha/TNFR1 and IFN/IFNR play an
      important role in the skin injury of SLE. The intracellular molecules including
      Syk and calcium/calmodulin 4 and NFAT are involved in the manifestation of skin
      damage in lupus-prone mice. UV is the most typical environmental factor to
      trigger skin injury in areas of IgG deposition in SLE. These evidences indicate
      that skin deposited IgG is a crucial pathological factor to trigger skin lesions
      in SLE and blockade of IgG signaling may be effective target against skin injury
      of SLE.

PMID- 29464449
TI  - Are Women's Orgasms Hindered by Phallocentric Imperatives?
AB  - Women who have sex with women (WSW) are more likely to report experiencing an
      orgasm during partnered sex, compared to women who have sex with men (WSM). We
      investigated whether this difference can be partially accounted for by
      phallocentric imperatives-gendered sexual scripts that prioritize men's sexual
      experience. For example, these imperatives emphasize vaginal-penile intercourse
      (i.e., the coital imperative) and men's physical pleasure (i.e., the male orgasm
      imperative). We reasoned that a larger variety of sexual behaviors indicates less
      adherence to the coital imperative and that more self-oriented orgasm goals for
      women indicate less adherence to the male orgasm imperative. Consistent with
      previous work, we expected WSW to report higher rates of orgasm than WSM when
      taking frequency of sex into account. We also hypothesized that this difference
      in orgasm rates would dissipate when controlling for variety of sexual behavior
      and women's self-oriented orgasm goals. In a sample of 1988 WSM and 308 WSW, we
      found that WSW were 1.33 times (p < .001) more likely to report experiencing an
      orgasm than WSM, controlling for frequency of sex. This incidence rate ratio was
      reduced to 1.16 (p < .001) after taking into account variety of sexual behavior
      and self-oriented orgasm goals. Our findings indicate that certain sexual scripts
      (e.g., phallocentric imperatives) help explain the orgasm discrepancy between WSW
      and WSM. We discuss masturbation as another male-centered practice that may be
      relevant to this gap, as well as implications for intervention and future
      research.

PMID- 29464448
TI  - Development and validation of an algorithm to identify drug-induced anaphylaxis
      in the Beijing Pharmacovigilance Database.
AB  - Background Pharmacovigilance databases are utilized to identify serious adverse
      drug events (ADEs). In China, very few studies have evaluated the validity of
      using pharmacovigilance databases to identify drug-induced anaphylaxis (DIA).
      Objective We aimed to develop and validate an algorithm to identify DIA using the
      Beijing Pharmacovigilance Database (BPD). Setting ADEs from the BPD mainly
      spontaneously reported from 94 hospitals in Beijing, China. Method Using the
      diagnoses, we developed an algorithm to identify potential DIAs from the BPD
      between January 2004 and December 2014. A sample of 500 patients was randomly
      selected for chart abstraction. Two physician adjudicators assessed whether DIA
      occurred using the published clinical criteria as the gold standard. Main outcome
      measure Positive predictive values (PPVs) and 95% confidence intervals of the
      algorithm and algorithm criteria components were calculated. Results 500 patients
      (53.2% female; the mean age 48.2 years) with potential DIA were selected using
      the algorithm. 444 were adjudicated as having anaphylaxis by physicians. The PPV
      of the overall algorithm was 88.8% (95% CI 86.0-91.6%). PPV for the algorithm
      only using specific diagnoses of "anaphylactic shock", "anaphylactic reaction",
      and "anaphylactoid reaction [severe]" was 89.6% (95% CI 86.6-92.4%); this partial
      algorithm identified 387 (87.2%) DIAs. The diagnosis that identified the most
      DIAs (83.8%) was "anaphylactic shock", with a PPV of 91.6% (95% CI 88.9-94.3%).
      Conclusion The overall algorithm identified a greater number of DIAs than the
      algorithm that only used specific diagnoses; however, its PPV was slightly lower.
      We were able to identify DIAs with the algorithm we developed.

PMID- 29464450
TI  - The Proof of the Pudding Is in the Tasting: Data Are Needed to Test Models and
      Hypotheses Related to Compulsive Sexual Behaviors.

PMID- 29464451
TI  - The Co-Occurrence of Asexuality and Self-Reported Post-Traumatic Stress Disorder
      Diagnosis and Sexual Trauma Within the Past 12 Months Among U.S. College
      Students.
AB  - An increasing number of individuals identify as asexual. It is important to
      understand the relationship between a diagnosis of post-traumatic stress disorder
      or a history of sexual trauma co-occurs with asexual identity. We aimed to assess
      whether identification as asexual was associated with greater likelihood for self
      reported PTSD diagnosis and history of sexual trauma within the past 12 months.
      Secondary data analysis was undertaken of a cross-sectional survey of 33,385 U.S.
      college students (12,148 male, 21,237 female), including 228 self-identified
      asexual individuals (31 male, 197 female), who completed the 2015-2016 Healthy
      Minds Study. Measures included assessment of self-report of prior professional
      diagnosis of PTSD and self-report of prior sexual trauma in the past year. Among
      non-asexual participants, 1.9% self-reported a diagnosis of PTSD and 2.4%
      reported a history of sexual trauma in the past 12 months. Among the group
      identified as asexual, 6.6% self-reported a diagnosis of PTSD and 3.5% reported a
      history of sexual assault in the past 12 months. Individuals who identified as
      asexual were more likely to report a diagnosis of PTSD (OR 4.44; 95% CI 2.32,
      8.50) and sexual trauma within the past 12 months (OR 2.52; 95% CI 1.20, 5.27),
      compared to non-asexual individuals. These differences persisted after including
      sex of the participants in the model, and the interaction between asexual
      identification and sex was not significant in either case. Asexual identity was
      associated with greater likelihood of reported PTSD diagnosis and reported sexual
      trauma within the past 12 months. Implications for future research on asexuality
      are discussed.

PMID- 29464452
TI  - Implicit and Explicit Associations with Erotic Stimuli in Women with and Without
      Sexual Problems.
AB  - Conceptual models of sexual functioning have suggested a major role for implicit
      cognitive processing in sexual functioning. The present study aimed to
      investigate implicit and explicit cognition in sexual functioning in women.
      Gynecological patients with (N = 38) and without self-reported sexual problems (N
      = 41) were compared. Participants performed two Single-Target Implicit
      Association Tests (ST-IAT), measuring the implicit association of visual erotic
      stimuli with attributes representing, respectively, valence and motivation.
      Participants also rated the erotic pictures that were shown in the ST-IATs on the
      dimensions of valence, attractiveness, and sexual excitement, to assess their
      explicit associations with these erotic stimuli. Participants completed the
      Female Sexual Functioning Index and the Female Sexual Distress Scale for
      continuous measures of sexual functioning, and the Hospital Anxiety and
      Depression Scale to assess depressive symptoms. Compared to nonsymptomatic women,
      women with sexual problems were found to show more negative implicit associations
      of erotic stimuli with wanting (implicit sexual motivation). Across both groups,
      stronger implicit associations of erotic stimuli with wanting predicted higher
      level of sexual functioning. More positive explicit ratings of erotic stimuli
      predicted lower level of sexual distress across both groups.

PMID- 29464453
TI  - Gender Expression and Mental Health in Black South African Men Who Have Sex with
      Men: Further Explorations of Unexpected Findings.
AB  - Unlike studies conducted in Western countries, two studies among Black South
      African men who have sex with men (MSM) found no support for the association
      between gender nonconformity and mental distress, even though gender
      nonconforming men experienced more discrimination and discrimination was
      associated with mental distress (Cook, Sandfort, Nel, & Rich, 2013; Sandfort,
      Bos, Knox, & Reddy, 2016). In Sandfort et al., gender nonconformity was assessed
      as a continuous variable, validated by comparing scores between a categorical
      assessment of gender presentation (masculine, feminine, no preference). Using the
      same dataset, we further explored this topic by (1) testing differences between
      gender expression groups in sexual minority stressors, resilience factors, and
      mental distress; (2) testing whether the impact of elevated discrimination in the
      feminine group was counterbalanced by lower scores on other stressors or higher
      scores on resilience factors; and (3) exploring whether relationships of
      stressors and resilience factors with mental distress varied between gender
      expression groups. Controlling for demographics, we found several differences
      between the gender expression groups in the stressors and resilience factors, but
      not in mental distress. We found no support for the idea that the lack of
      differences in mental distress between the gender expression groups was a
      consequence of factors working in opposite directions. However, internalized
      homophobia had a differential impact on depression in feminine men compared to
      masculine men. In our discussion of these findings, we explored the meaning of
      our participants' self-categorization as it might relate to gender instead of
      sexual identities.

PMID- 29464454
TI  - Never Been Kissed: Correlates of Lifetime Kissing Status in U.S. University
      Students.
AB  - Kissing a partner occurs relatively early during adolescence. Thus, young adults
      who have never kissed are off-time from their peers. Substantial exploration in
      the areas of identity and intimacy occur during this period, and kissing may
      fulfill both of these functions, addressing autonomy and relatedness motives for
      sexual behaviors. We examined the prevalence and personal, contextual, and
      adjustment/health predictors of delayed onset of kissing. An ethnically and
      racially diverse sample of traditionally aged first year university students (N =
      738; 50.7% female) completed online surveys. Only 14.2% of young adults had never
      kissed a partner on the lips. Compared to their peers who had kissed partners,
      young adults who had never kissed were more likely to be Asian-American, less
      likely to be in a romantic relationship, were less extraverted, were more likely
      to be in the Honors College, and drank alcohol less frequently. In bivariate
      models but not the multivariate model, young adults who had never kissed were
      more neurotic, had mothers who were less facilitating of independence, and had
      lower self-esteem. Findings inform understanding of normative sexuality
      development, and inform future research on normative and off-time sexual
      behaviors in young adulthood.

PMID- 29464455
TI  - "And Then Break the Cliche": Understanding and Addressing HIV Vulnerability
      Through Development of an HIV Prevention Telenovela with Men Who Have Sex with
      Men and Transwomen in Lima, Peru.
AB  - HIV and other sexually transmitted infections (STIs) continue to affect men who
      have sex with men (MSM) and transgender women (TW) in Peru at disproportionately
      high rates. The ineffectiveness of traditional prevention strategies may be due
      to the disconnect between health promotion messages and community-level
      understandings of sexual cultures. We conducted 15 workshops with MSM and TW to
      develop a community-based sexual health intervention. Intervention development
      consisted of focus groups and scenic improvisation to identify sexual scripts for
      an HIV prevention telenovela, or Spanish soap opera. Workshops were stratified by
      self-reported socioeconomic status, sexual orientation, and gender identity: (1)
      low-income MSM (n = 9); (2) middle/high-income MSM (n = 6); and (3) TW (n = 8).
      Employing a conceptual model based on sexual scripts and critical consciousness
      theories, this paper reports on three themes identified during the telenovela
      development process as participants sought to "rescript" social and sexual
      stereotypes associated with HIV-related vulnerability: (1) management of MSM and
      TW social identities at the intersection of socioeconomic status, sexuality, and
      gender performance; (2) social constructions of gender and/or sexual role and
      perceived and actual HIV/STI risk(s) within sexual partnership interactions; and
      (3) idealized and actual sexual scripts in the negotiation of safer sex practices
      between MSM/TW and their partners. These findings are key to reframing existing
      prevention strategies that fail to effectively engage poorly defined "high-risk
      populations." Leveraging community-based expertise, the results provide an
      alternative to the static transfer of information through expert-patient
      interactions in didactic sessions commonly used in HIV prevention interventions
      among MSM and TW.

PMID- 29464456
TI  - Application of validity theory and methodology to patient-reported outcome
      measures (PROMs): building an argument for validity.
AB  - BACKGROUND: Data from subjective patient-reported outcome measures (PROMs) are
      now being used in the health sector to make or support decisions about
      individuals, groups and populations. Contemporary validity theorists define
      validity not as a statistical property of the test but as the extent to which
      empirical evidence supports the interpretation of test scores for an intended
      use. However, validity testing theory and methodology are rarely evident in the
      PROM validation literature. Application of this theory and methodology would
      provide structure for comprehensive validation planning to support improved PROM
      development and sound arguments for the validity of PROM score interpretation and
      use in each new context. OBJECTIVE: This paper proposes the application of
      contemporary validity theory and methodology to PROM validity testing.
      ILLUSTRATIVE EXAMPLE: The validity testing principles will be applied to a
      hypothetical case study with a focus on the interpretation and use of scores from
      a translated PROM that measures health literacy (the Health Literacy
      Questionnaire or HLQ). DISCUSSION: Although robust psychometric properties of a
      PROM are a pre-condition to its use, a PROM's validity lies in the sound argument
      that a network of empirical evidence supports the intended interpretation and use
      of PROM scores for decision making in a particular context. The health sector is
      yet to apply contemporary theory and methodology to PROM development and
      validation. The theoretical and methodological processes in this paper are
      offered as an advancement of the theory and practice of PROM validity testing in
      the health sector.

PMID- 29464457
TI  - Cloning and characterization of the human lactoferrin receptor gene promoter.
AB  - Lactoferrin (Lf) is a major protein in human milk. Multiple biological functions
      of Lf are postulated to be mediated by a Lf receptor (LfR). The Lf receptor (LfR)
      plays an important role in absorption of Lf and Lf-bound iron by intestinal
      epithelial cells. Here, we cloned and characterized the promoter from a ~ 3.1 kb
      5'-flanking region of the human LfR gene. Neither a TATA box nor a CCAAT box is
      found at the typical positions. The transcription start site was identified as
      298 bp upstream of the translation start codon (+ 1) by 5' RLM-RACE. A series of
      deletions of 5'-flanking sequences of the human LfR gene were cloned into a
      promoter-less pGL3 luciferase reporter and transiently transfected into an
      intestinal enterocyte model (Caco-2 cells). A fragment of - 299/+ 63 elicited the
      maximal promoter activity in transfected Caco-2 cells, suggesting that functional
      transcription factor binding sites appear in the region of - 299/+ 63.
      Bioinformatics analysis indicates that the - 299/+ 63 fragment contains two
      putative Sp1 binding sites. The promoter activity was significantly decreased
      when the Sp1 binding sites were mutated by site-directed mutagenesis.
      Additionally, the promoter activity was dramatically inhibited by treating cells
      with an Sp1 inhibitor. Binding of Sp1 to the promoter was confirmed by EMSA.
      Moreover, after Sp1 expression was significantly suppressed by RNA interference,
      LfR was significantly decreased at both RNA and protein levels. In conclusion,
      the LfR gene promoter contains downstream core promoter elements, and the Sp1
      binding sites play critical roles in transcriptional regulation of the LfR gene.

PMID- 29464458
TI  - PFO closure for secondary stroke prevention: is the discussion closed?
AB  - Three previous reports of PFO closure for secondary stroke prevention failed to
      find any significant benefit. Recently however, three conflicting reports were
      published suggesting a benefit in select patients. Although we are enthusiastic
      for PFO closure in appropriate patients, caution is warranted in the
      extrapolation of this data and the application of this intervention to broader
      patient groups. Only small minorities of stroke patients are likely to benefit
      from PFO closure, the intervention has a notable complication rate, and it has
      not been compared against modern anticoagulation options. Clinicians should
      consider all of these points as discussions around PFO closure are likely to
      become more and more common going forward.

PMID- 29464459
TI  - A Diaper Pad for Diaper-Based Urine Collection and Colorimetric Screening of
      Urinary Biomarkers.
AB  - The high prevalence of urinary tract infection in aging adults is a challenging
      aspect of geriatric care. Incontinence and cognitive/functional impairment make
      collection of urine samples difficult and often require either catheterization
      for sample collection, which is a risk factor for infections, or more lenient
      criteria for initiating antibiotic treatment. We report the development of a
      diaper inlay with absorbent materials, superabsorbent polymer-based valve and
      chemical reaction pads for rapid screening of urinary tract infection of
      incontinent diaper-wearing elderly receivers of home care services. The developed
      diaper inlay was capable of collecting, isolating, analyzing samples and
      retaining results > 8 h. The diaper inlay can therefore be compatible with the
      diaper changing routines of nurses in home care services, without requiring much
      time or effort. A nurse can insert a diaper inlay in a diaper and the results can
      be recorded during a later diaper change. Although the research focuses on tools
      for home care services, the nursing home sector has similar problems and may
      benefit from technological development for rapid screening to avoid unnecessary
      catheterization and overuse of antibiotics.

PMID- 29464460
TI  - Effects of Hollow Fiber Membrane Oscillation on an Artificial Lung.
AB  - Gas transfer through hollow fiber membranes (HFMs) can be increased via fiber
      oscillation. Prior work, however, does not directly translate to present-day,
      full-scale artificial lungs. This in vitro study characterized the effects of HFM
      oscillations on oxygenation and hemolysis for a pediatric-sized HFM bundle.
      Effects of oscillation stroke length (2-10 mm) and frequency (1-25 Hz) on oxygen
      transfer were measured according to established standards. The normalized index
      of hemolysis was measured for select conditions. All measurements were performed
      at a 2.5 L min-1 blood flow rate. A lumped parameter model was used to predict
      oscillation-induced blood flow and elucidate the effects of system parameters on
      oxygenation. Oxygen transfer increased during oscillations, reaching a maximum
      oxygenation efficiency of 510 mL min-1 m-2 (97% enhancement relative to no
      oscillation). Enhancement magnitudes matched well with model-predicted trends and
      were dependent on stroke length, frequency, and physical system parameters. A 40%
      oxygenation enhancement was achieved without significant hemolysis increase. At a
      constant enhancement magnitude, a larger oscillation frequency resulted in
      increased hemolysis. In conclusion, HFM oscillation is a feasible approach to
      increasing artificial lung gas transfer efficiency. The optimal design for
      maximizing efficiency at small fiber displacements should minimize bundle
      resistance and housing compliance.

PMID- 29464461
TI  - Tactile Feedback can be Used to Redistribute Flexion Motion Across Spine Motion
      Segments.
AB  - This experiment investigates the efficacy of tactile feedback in affecting
      changes to dynamic spine movements. A sample of (n = 24) young, healthy males
      were assessed while completing targeted spine flexion movements with instruction
      to minimize stretching of the skin beneath an applied tactile stimulus (liquid
      bandage). Localized tactile stimuli were placed bilaterally at either lumbar
      (L4), lower thoracic (T10) or upper thoracic (T4) levels. Results demonstrate
      that localized tactile feedback elicited a re-distribution of spine flexion
      movement across spine sub-sections (e.g. lumbar vs. thoracic) and intervertebral
      segments (e.g. C7/T1 through L5/S1). Further, tactile feedback successfully
      limited the magnitude of end-range flexion, but did not limit functional mid
      range spine flexion. Finally, tactile feedback located in the lower thoracic
      region (T10) increased thoracic flexion variability; however, tactile feedback
      located at the T4 and L4 regions had no significant effect on movement
      variability. These findings provide evidence that spine neuromuscular control
      patterns can be altered using simple tactile stimuli. In terms of low back injury
      prevention and/or rehabilitation, the tactile feedback investigated here has
      apparent utility in limiting recognized mechanical risk factors for low back
      injury; specifically, the local incidence of flexion at specific spine levels,
      and the incidence of end-range flexion.

PMID- 29464462
TI  - Gestational and lactational exposure to dichlorinated bisphenol A induces early
      alterations of hepatic lipid composition in mice.
AB  - OBJECTIVE: Using non-invasive magnetic resonance (MR) techniques and a
      histological approach, we assessed the outcomes of perinatal exposure at a low
      dose of 3,3'-DCBPA (2-chloro-4-[1-(3-chloro-4-hydroxyphenyl)-1
      methylethyl]phenol) and/or 3,5-DCBPA (2,6-dichloro-4-[1-(4-hydroxyphenyl)-1
      methylethyl]phenol) on mice livers. MATERIALS AND METHODS: Fertilized female
      Swiss mice were injected intraperitoneally during gestation and lactation with
      either vehicle control, 20 MUg/kg/day of BPA, 3,5-DCBPA, 3,3'-DCBPA or a mixture
      (mix-DCBPA). Complementary methods were used to evaluate, in male and female
      pups, (1) liver structure by texture analysis of images obtained through MR
      imaging (MRI) and histology, (2) hepatic lipid composition through in vivo 1H MR
      spectroscopy (1H MRS). RESULTS: Principal component analysis of texture
      parameters showed no structural modification of the liver with BPA and DCBPA
      treatments. Accordingly, no hepatic microvesicular steatosis was observed through
      hematoxylin-eosin staining. Compared to control, MRS revealed no difference in
      lipid composition for BPA, 3,5-DCBPA or 3,3'-DCBPA groups. However, MRS detected
      a significant increase in the mix-DCBPA groups for the saturated component of
      fatty acids (FA), total unsaturated FA bond index and polyunsaturated FA bond
      index. CONCLUSION: Prior to any structural changes, polyunsaturated fatty acids
      significantly increased in young male and female mice exposed perinatally at a
      low dose to a mixture of dichlorinated BPA.

PMID- 29464463
TI  - The impact of fibre orientation on T1-relaxation and apparent tissue water
      content in white matter.
AB  - OBJECTIVE: Recent MRI studies have shown that the orientation of nerve fibres
      relative to the main magnetic field affects the R2*(= 1/T2*) relaxation rate in
      white matter (WM) structures. The underlying physical causes have been discussed
      in several studies but are still not completely understood. However,
      understanding these effects in detail is of great importance since this might
      serve as a basis for the development of new diagnostic tools and/or improve
      quantitative susceptibility mapping techniques. Therefore, in addition to the
      known angular dependence of R2*, the current study investigates the relationship
      between fibre orientation and the longitudinal relaxation rate, R1 (= 1/T1), as
      well as the apparent water content. MATERIALS AND METHODS: For a group of 16
      healthy subjects, a series of gradient echo, echo-planar and diffusion weighted
      images were acquired at 3T from which the decay rates, the apparent water content
      and the diffusion direction were reconstructed. The diffusion weighted data were
      used to determine the angle between the principle fibre direction and the main
      magnetic field to examine the angular dependence of R1 and apparent water
      content. RESULTS: The obtained results demonstrate that both parameters depend on
      the fibre orientation and exhibit a positive correlation with the angle between
      fibre direction and main magnetic field. CONCLUSION: These observations could be
      helpful to improve and/or constrain existing biophysical models of brain
      microstructure by imposing additional constraints resulting from the observed
      angular dependence R1 and apparent water content in white matter.

PMID- 29464464
TI  - Pazopanib-related tumor lysis syndrome in metastatic clear cell renal cell
      carcinoma: a case report.
AB  - Introduction Tumor lysis syndrome (TLS) is a life-threatening emergency caused by
      rapid cell death as a result of anti-tumor therapy. In the era of targeted
      therapy it has increasingly been observed in solid malignancies such as
      hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). Case We describe
      the case of a 58-year old man with the medical history of a memorial sloan
      kettering cancer centre (MSKCC) poor prognosis metastasized clear cell renal cell
      carcinoma (mRCC) who developed TLS within six days after initiating therapy with
      the tyrosine kinase inhibitor (TKI) pazopanib. Discussion The pharmacokinetics
      and pharmacodynamics of pazopanib are complex and characterized by a non-linear
      and time-dependent bioavailability. Pazopanib is almost completely bound to serum
      albumin (>99.9%). In this presented case, a low serum albumin (26 g/L) might have
      led to a higher free fraction of pazopanib, which could have resulted in more
      toxicity. Also, pazopanib is metabolised by the CYP3A4 isoform of the cytochrome
      P450 group. Low quantities of this enzyme may lead to an impaired and prolonged
      breakdown of the drug. Conclusion As far as we know this is the first report on
      pazopanib induced TLS. We advise further research in order to identify the exact
      mechanism behind TKI-induced TLS and the patients at risk of developing TLS.

PMID- 29464465
TI  - The concomitant use of lapatinib and paracetamol - the risk of interaction.
AB  - Lapatinib is a tyrosine kinase inhibitor used for the treatment of breast cancer.
      Paracetamol is an analgesic commonly applied to patients with mild or moderate
      pain and fever. Cancer patients are polymedicated, which involves high risk of
      drug interactions during therapy. The aim of the study was to assess the
      interaction between lapatinib and paracetamol in rats. The rats were divided into
      three groups of eight animals in each. One group received lapatinib + paracetamol
      (IL + PA), another group received lapatinib (IIL), whereas the last group
      received paracetamol (IIIPA). A single dose of lapatinib (100 mg/kg b.w.) and
      paracetamol (100 mg/kg b.w.) was administered orally. Plasma concentrations of
      lapatinib, paracetamol and its metabolites - glucuronide and sulphate, were
      measured with the validated HPLC-MS/MS method and HPLC-UV method, respectively.
      The pharmacokinetic parameters of both drugs were calculated using non
      compartmental methods. The co-administration of lapatinib and paracetamol
      increased the area under the plasma concentration-time curve (AUC) and the
      maximum concentration (Cmax) of lapatinib by 239.6% (p = 0.0030) and 184% (p =
      0.0011), respectively. Lapatinib decreased the paracetamol AUC0-infinity by 48.8%
      and Cmax by 55.7%. In the IL + PA group the Cmax of paracetamol glucuronide was
      reduced, whereas the Cmax of paracetamol sulphate was higher than in the IIIPA
      group. Paracetamol significantly affected the enhanced plasma exposure of
      lapatinib. Additionally, lapatinib reduced the concentrations of paracetamol. The
      co-administration of lapatinib decreased the paracetamol glucuronidation but
      increased the sulphation. The findings of this study may be of clinical relevance
      to patients requiring analgesic therapy.

PMID- 29464466
TI  - WhichP450: a multi-class categorical model to predict the major metabolising
      CYP450 isoform for a compound.
AB  - In the development of novel pharmaceuticals, the knowledge of how many, and
      which, Cytochrome P450 isoforms are involved in the phase I metabolism of a
      compound is important. Potential problems can arise if a compound is metabolised
      predominantly by a single isoform in terms of drug-drug interactions or genetic
      polymorphisms that would lead to variations in exposure in the general
      population. Combined with models of regioselectivities of metabolism by each
      isoform, such a model would also aid in the prediction of the metabolites likely
      to be formed by P450-mediated metabolism. We describe the generation of a multi
      class random forest model to predict which, out of a list of the seven leading
      Cytochrome P450 isoforms, would be the major metabolising isoforms for a novel
      compound. The model has a 76% success rate with a top-1 criterion and an 88%
      success rate for a top-2 criterion and shows significant enrichment over
      randomised models.

PMID- 29464467
TI  - Insight into the molecular mechanism of yeast acetyl-coenzyme A carboxylase
      mutants F510I, N485G, I69E, E477R, and K73R resistant to soraphen A.
AB  - Acetyl-coenzyme A carboxylases (ACCs) is the first committed enzyme of fatty acid
      synthesis pathway. The inhibition of ACC is thought to be beneficial not only for
      diseases related to metabolism, such as type-2 diabetes, but also for infectious
      disease like bacterial infection disease. Soraphen A, a potent allosteric
      inhibitor of BC domain of yeast ACC, exhibit lower binding affinities to several
      yeast ACC mutants and the corresponding drug resistance mechanisms are still
      unknown. We report here a theoretical study of binding of soraphen A to wild type
      and yeast ACC mutants (including F510I, N485G, I69E, E477R, and K73R) via
      molecular dynamic simulation and molecular mechanics/generalized Born surface
      area free energy calculations methods. The calculated binding free energies of
      soraphen A to yeast ACC mutants are weaker than to wild type, which is highly
      consistent with the experimental results. The mutant F510I weakens the binding
      affinity of soraphen A to yeast ACC mainly by decreasing the van der Waals
      contributions, while the weaker binding affinities of Soraphen A to other yeast
      ACC mutants including N485G, I69E, E477R, and K73R are largely attributed to the
      decreased net electrostatic (DeltaEele + DeltaGGB) interactions. Our simulation
      results could provide important insights for the development of more potent ACC
      inhibitors.

PMID- 29464468
TI  - Elderly Fitz-Hugh-Curtis syndrome observed with superb microvascular imaging
      system.
AB  - Fitz-Hugh-Curtis syndrome (FHCS) is defined as inflammation on the surface of the
      liver following sexually transmitted chlamydia infection. We successfully
      observed the microvascular structure of the inflamed portion between the
      abdominal wall and surface of the liver in an elderly patient with FHCS using a
      superb microvascular imaging (SMI) system, a new technology developed for
      observing minute vascular flow. An 80-year-old Japanese female with right dorsal
      to lateral abdominal pain and fever came to our hospital. Anti-chlamydia
      antibodies were positive. SMI revealed signals suggesting small vessels passing
      from the liver surface to the hypoechoic space.

PMID- 29464469
TI  - Ultrasonographic images of the hand in a case with early eosinophilic fasciitis.
AB  - Eosinophilic fasciitis (EF), a rare rheumatic disease, usually affects the limbs
      symmetrically and generally spares the hands and feet. Cases of unilateral hand
      involvement are rarely reported. Here, we report such a rare case.
      Ultrasonography demonstrated thickening of the overlying skin and subcutaneous
      tissue, peripheral deep fascia, myositis of lumbrical muscles and adductor
      pollicis muscle, and edema surrounding flexor digitorum tendons. It reminds us
      that EF should be considered in the differential diagnosis of unilateral painful
      hand swelling despite being uncommon. Ultrasonography can be used to aid the
      diagnosis and monitor therapeutic response in patients with EF.

PMID- 29464470
TI  - Open flap versus flapless placement of dental implants. A randomized controlled
      pilot trial.
AB  - The aim of this study was to compare the immediate postoperative period of
      participants rehabilitated with dental implants placed with a conventional
      technique or with a minimally invasive technique, without a mucoperiosteal flap
      elevation (flapless). Participants who needed implant placement were divided into
      two groups: one group was operated using a mucoperiosteal flap elevation (G_A),
      and the other with a flapless surgical technique (G_B). Objective clinical
      parameters including oral hygiene, mouth opening, inflammation (facial
      perimeter), surgical time and analgesic consumption, as well as subjective
      parameters of pain and degree of satisfaction with the procedure, were evaluated.
      48 implants were placed in 30 participants (15 participants per group). Oral
      hygiene index, maximum interincisal opening, pain and analgesic consumption
      values had a significant difference between groups favoring the flapless
      technique at 24 h and 7 days but at the 15 days' follow-up the differences were
      only significant for oral hygiene and pain (P < 0.05); there were no
      statistically significant differences between groups in terms of facial perimeter
      values and surgical time (P > 0.05). Average on the degree of satisfaction was of
      2.6 (SD 0.8) for G_A and 3.6 (SD 1.02) for G_B (P = 0.06). One implant placed in
      G_A (2.0%) failed before prosthetic loading due to mobility and pain at 3 months'
      follow-up. Participants operated for implant placement with flapless surgical
      technique go through less postoperative discomfort. Both techniques show high
      success rates, but to perform a flapless technique patients must be properly
      selected.

PMID- 29464472
TI  - "Lethal talk or healthful words? The prescription for empathetic utterance".

PMID- 29464471
TI  - Correction to: Effects of periodontal treatment on carotid intima-media thickness
      in patients with lifestyle-related diseases: Japanese prospective multicentre
      observational study.
AB  - Unfortunately, in Table-5 of the original article, the parameter in the 5th row
      was published incorrectly as "LDL-C (mg/dL)". The correct parameter should read
      as "HDL-C (mg/dL)".

PMID- 29464474
TI  - The Long-Term Uninsured Were Less Likely than the Short-Term Uninsured to Gain
      Insurance in 2014.

PMID- 29464473
TI  - So Tired: Predictive Utility of Baseline Sleep Screening in a Longitudinal
      Observational Survey Cohort of First-Year Residents.
AB  - BACKGROUND: Sleep impairment is highly prevalent among resident physicians and is
      associated with both adverse patient outcomes and poor resident mental and
      physical health. Risk factors for sleep problems during residency are less clear,
      and no screening model exists to identify residents at risk for sleep impairment.
      OBJECTIVE: The objective of this study was to assess change in resident sleep
      during training and to evaluate utility of baseline sleep screening in predicting
      future sleep impairment. DESIGN: This is a prospective observational repeated
      measures survey study. PARTICIPANTS: The participants comprised PGY-1 residents
      across multiple specialties at Partners HealthCare hospitals. MAIN MEASURES: Main
      measures used for this study were demographic queries and two validated scales:
      the Pittsburgh Sleep Quality Index (PSQI), measuring sleep quality, and the
      Epworth Sleepiness Scale (ESS), measuring excessive daytime sleepiness. KEY
      RESULTS: Two hundred eighty-one PGY-1 residents completed surveys at residency
      orientation, and 153 (54%) completed matched surveys 9 months later. Mean nightly
      sleep time decreased from 7.6 to 6.5 hours (p < 0.001). Mean PSQI score increased
      from 3.6 to 5.2 (p < 0.001), and mean ESS score increased from 7.2 to 10.4 (p <
      0.001). The proportion of residents exceeding the scales' clinical cutoffs
      increased over time from 15 to 40% on the PSQI (p < 0.001) and from 26 to 59% on
      the ESS (p < 0.001). Baseline normal sleep was not protective: 68% of residents
      with normal scores on both scales at baseline exceeded the clinical cutoff on at
      least one scale at follow-up. Greater age and fewer children increased follow-up
      PSQI score (p < 0.001) but not ESS score. CONCLUSIONS: During PGY-1 training,
      residents experience worsening sleep duration, quality of sleep, and daytime
      sleepiness. Residents with baseline impaired sleep tend to remain impaired.
      Moreover, many residents with baseline normal sleep experience sleep
      deterioration over time. Sleep screening at residency orientation may identify
      some, but not all, residents who will experience sleep impairment during
      training.

PMID- 29464475
TI  - Seasonal Variation in Readmission Risk for Patients Hospitalized with
      Cardiopulmonary Conditions.

PMID- 29464476
TI  - Can your patients with heart failure see? The prevalence of visual impairment
      among adults with heart failure.

PMID- 29464477
TI  - Capsule Commentary on Bremmer et. al., Impact of Procalcitonin Guidance on
      Management of Adults Hospitalized with Chronic Obstructive Pulmonary Disease
      Exacerbations.

PMID- 29464478
TI  - An All-Payer Risk Model for Super-Utilization in a Large Safety Net System.

PMID- 29464480
TI  - Events.

PMID- 29464479
TI  - FDG-PET/CT at the end of immuno-chemotherapy in follicular lymphoma: the
      prognostic role of the ratio between target lesion and liver SUVmax (rPET).
AB  - AIM: To retrospectively investigate the prognostic role of the ratio between
      target lesion and liver SUVmax (rPET) in patients with follicular lymphoma (FL)
      submitted to FDG-PET/CT at the end of immuno-chemotherapy (PI-PET), and to
      compare rPET with International Harmonization Project criteria (IHP), Deauville
      Score (5p-DS) and FL International Prognostic Index at diagnosis (FLIPI).
      METHODS: Eighty-nine patients with FL undergoing PI-PET were evaluated. The
      receiver operating characteristic (ROC) approach was applied to identify the
      optimal cut-point of rPET with respect to 5-years progression free survival
      (PFS). The prognostic significance of rPET was compared with IHP, DS and FLIPI.
      Positive predictive value (PPV) and negative predictive value (NPV) were
      calculated using the presence of adverse events as gold standard. RESULTS: The
      ROC analysis for rPET as predictor of progression showed an optimal rPET cut
      point of 0.98. Patients with positive values of IHP, DS and rPET had a PFS of 50,
      30 and 31%. PPV were of 56, 80 and 80%, NPV of 83, 86 and 88%, respectively. DS
      and rPET differed only in two patients. FLIPI was not predictive of progression
      and relapse. CONCLUSIONS: rPET is a prognostic factor in patients with FL
      submitted to PI-PET. Although it has a similar prognostic power as DS, it can
      have methodological advantages over visual analysis. PI-PET with different
      evaluation systems has a stronger prognostic power than FLIPI at diagnosis, so it
      could be useful to identify patients with FL at risk for early relapse after
      immuno-chemotherapy.

PMID- 29464482
TI  - 2017 Outstanding Reviewers.

PMID- 29464481
TI  - What Kills Science in School?: Lessons from Pre-Service Teachers' Responses to
      Urban children's Science Inquiries.
AB  - This opportunistic case-study highlights striking differences in 6 urban
      children's and 12 preservice suburban middle-class teachers' perception of
      science and discuss consequences of science education and beyond. I found that
      all of the interviewed urban children demonstrated scientific inquiries and
      interests outside of the school science education that can be characterized by
      diverse simultaneous discourses from diverse practices, i.e., "heterodiscoursia"
      (Matusov in Culture & Psychology, 17(1), 99-119, 2011b), despite their diverse,
      positive and negative, attitudes toward school science. In contrast to the urban
      children's mixed attitudes to science, the preservice teachers view science
      negatively. They could not see science inquiries in the videotaped interviews of
      the urban children. There seemed to be many reasons for that. One of the possible
      reasons for that was that the preservice teachers tried to purify the science
      practice. Another reason was that they did not see a necessity to be interested
      and engaged in the curriculum that they are going to teach in future. The
      pedagogical consequences and remedies are discussed.

PMID- 29464483
TI  - Mutational subtypes of JAK2 and CALR correlate with different clinical features
      in Japanese patients with myeloproliferative neoplasms.
AB  - The majority of patients with Philadelphia chromosome-negative myeloproliferative
      neoplasms (MPNs) harbor JAK2, CALR, or MPL mutations. We compared clinical
      manifestations of different subtypes of JAK2 and CALR mutations in Japanese
      patients with MPNs. Within our cohort, we diagnosed 166 patients as polycythemia
      vera (PV), 212 patients as essential thrombocythemia (ET), 23 patients as pre
      primary myelofibrosis (PMF), 65 patients as overt PMF, and 27 patients as
      secondary myelofibrosis following the 2016 WHO criteria. Compared to patients
      with JAK2V617F-mutated PV, JAK2 exon 12-mutated PV patients were younger, showed
      lower white blood cell (WBC) counts, lower platelet counts, higher red blood cell
      counts, and higher frequency of thrombotic events. Compared to JAK2-mutated ET
      patients, CALR-mutated ET patients were younger, showed lower WBC counts, lower
      hemoglobin levels, higher platelet counts, and fewer thrombotic events. CALR type
      1-like mutation was the dominant subtype in CALR-mutated overt PMF patients.
      Compared with JAK2V617F-mutated ET patients, JAK2V617F-mutated pre-PMF patients
      showed higher LDH levels, lower hemoglobin levels, higher JAK2V617F allele
      burden, and higher frequency of splenomegaly. In conclusion, Japanese patients
      with MPNs grouped by different mutation subtypes exhibit characteristics similar
      to those of their Western counterparts. In addition, ET and pre-PMF patients show
      different characteristics, even when restricted to JAK2V617F-mutated patients.

PMID- 29464484
TI  - Characteristics and outcome of chronic myeloid leukemia patients with E255K/V BCR
      ABL kinase domain mutations.
AB  - Kinase domain (KD) mutations of ABL1 represent the most common resistance
      mechanism to tyrosine kinase inhibitors (TKI) in CML. Besides T315I, mutations in
      codon 255 are highly resistant mutations in vitro to all TKI. We aimed to study
      the incidence, prognosis, and response to treatment in patients with E255K/V. We
      evaluated 976 patients by sequencing of BCR-ABL1 fusion transcript for ABL1 KD
      mutations. We identified KD mutations in 381 (39%) patients, including E255K/V in
      48 (13% of all mutations). At mutation detection, 14 patients (29%) were in
      chronic phase (CP), 12 (25%) in accelerated phase (AP), and 22 (46%) in blast
      phase (BP). 9/14 CP patients responded to treatment (best response complete
      hematologic response-CHR-4; complete cytogenetic response-CCyR-1; major molecular
      response-MMR-4); only 4/12 AP patients (CHR 3; MMR 1) and 7/22 BP patients
      responded (CCyR 2; MMR 2; partial cytogenetic response-PCyR-3). After a median
      follow-up of 65 months from mutation detection, 36 patients (75%) died: 9/14
      (64%) in CP, 9/12 (75%) in AP, and 18/22 (82%) in BP (p = 0.003); median overall
      survival was 12 months. Patients with E255K/V mutation have a poor prognosis,
      regardless of the stage of the disease at detection.

PMID- 29464485
TI  - Determining the Roles of a Conserved alpha-Helix in a Global Virulence Regulator
      from Staphylococcus aureus.
AB  - SarA, a pleiotropic transcription regulator, is encoded by Staphylococcus aureus,
      a pathogenic bacterium. The expression of many virulence and non-virulence genes
      in S. aureus is modulated by this regulator. Structural studies have shown it to
      be a winged-helix DNA-binding protein carrying two monomers. Each SarA monomer is
      composed of five alpha-helices (alpha1-alpha5), three beta-strands (beta1-beta3)
      and multiple loops. The putative DNA binding region of SarA is constituted with
      alpha3, alpha4, beta2, and beta3, whereas, its dimerization seems to occur using
      alpha1, alpha2, and alpha5. Interestingly, many SarA-like proteins are dimeric
      and use three or more helices for their dimerization. To clearly understand the
      roles of helix alpha1 in the dimerization, we have constructed and purified a
      SarA mutant (Deltaalpha1) that lacks helix alpha1. Our in-depth studies with
      Deltaalpha1 indicate that the helix alpha1 is critical for preserving the
      structure, DNA binding activity and thermodynamic stability of SarA. However, the
      helix has little affected its dimerization ability. Possible reasons for such
      anomaly have been discussed at length.

PMID- 29464487
TI  - Binocular visual function of myopic pseudophakic monovision.
AB  - PURPOSE: To compare binocular visual function of myopic pseudophakic patients
      with myopic monovision to patients without monovision. STUDY DESIGN: Randomized
      comparative study METHODS: Sixty patients were randomized to one of two groups:
      patients whose refraction was targeted to -2.75 diopters (D) in the dominant eye
      and -1.75D in the nondominant eye (myopic monovision group), and patients whose
      refraction was targeted to -2.75D bilaterally (non-monovision group). Binocular
      uncorrected and corrected visual acuity at various distances was measured using
      an all-distance vision tester, and contrast visual acuity and near stereoacuity
      were examined. RESULTS: In the myopic monovision group mean refraction was -2.74D
      in the dominant eyes and -1.94D in the nondominant eyes, and in the non
      monovision group it was -2.96D bilaterally. Mean binocular uncorrected distance
      (UDVA) and intermediate visual acuity (UIVA) from 0.5 m to 5.0 m were
      significantly better in the myopic monovision group than in the non-monovision
      group (P<= 0.0134), while binocular uncorrected near visual acuity (UNVA) at 0.3
      m did not differ significantly between groups. The distribution of UIVA and UDVA
      was significantly better in the myopic monovision group (P<= 0.0035). Corrected
      visual acuity at any distance, photopic and mesopic contrast visual acuity, and
      stereoacuity did not differ significantly between groups. CONCLUSION: Patients
      with myopic monovision exhibited significantly better binocular UIVA and UDVA
      than those without monovision, while UNVA, corrected visual acuity, contrast
      sensitivity, and stereoacuity were comparable between groups, suggesting that
      this method is useful for patients who want to see near and intermediate
      distances without spectacles.

PMID- 29464486
TI  - MicroRNA-322 Cluster Promotes Tau Phosphorylation via Targeting Brain-Derived
      Neurotrophic Factor.
AB  - Brain-derived neurotrophic factor (BDNF) is a crucial regulator to support
      synaptic plasticity and neuronal survival, its significant decrease is a
      pathophysiological hallmark in Alzheimer's disease (AD) brains and accounts for
      poor prognosis. MicroRNAs (miRNAs) interfere with the translation of target mRNAs
      and control a variety of physiological and pathological processes. MiR-322 is the
      rodent homologue of human miR-424, it is involved in the modulation of cell
      differentiation, proliferation, apoptosis and metabolic activities in diverse
      tissues and organs. However, the roles and potential mechanisms of miR-322 remain
      elusive in AD pathogenesis. Here we observed miR-322 is significantly increased
      along with BDNF decrease in AD mouse brain. Bioinformatics prediction implicated
      that BDNF 3'-untranslated region (3'-UTR) possesses the putative target sequence
      of miR-322. Luciferase reporter assay identified that miR-322 can directly
      conjugate to BDNF 3'-UTR. The functional research showed that MiR-322 input
      deregulates BDNF expression at either mRNA or protein levels, whereas miR-322
      silence restores BDNF expression in vitro. Furthermore, we found miR-322 promotes
      Tau phosphorylation via negatively controlling BDNF-TrkB receptor activation,
      otherwise MiR-322 silence restores TrkB activation and attenuates tau
      phosphorylation. Collectively, this study demonstrated a novel miRNA-dependent
      manner of BDNF degradation in AD pathogenesis, it may drive a miRNAs- or BDNF
      based therapeutic strategies against Alzheimer's disease.

PMID- 29464488
TI  - Reinforced scleral fixation of foldable intraocular lens by double sutures:
      comparison with intrascleral intraocular lens fixation.
AB  - PURPOSE: The purpose of this study is to describe a new technique for small
      incision scleral fixation of intraocular lens (IOL) using double 10-0
      polypropylene sutures, and to report the outcomes of IOL position compared with
      intrascleral IOL fixation at 12-month follow-up. STUDY DESIGN: A retrospective
      comparative study. METHOD: This new technique, called double sutured scleral
      fixated-IOL (DSF-IOL), was created to help with long-term knots strengthening by
      applying double sutures to each IOL haptic using an augmented Clove-hitch knot
      instead of the conventional knots tied by single suture. The tilt and decenter of
      IOL were measured by Scheimpflug camera and other refractive outcomes were
      compared between two groups at 12-month follow-up. RESULTS: This study consisted
      of 26 eyes (54.2%) from the DSF-IOL group, and 22 eyes (45.8%) from the
      intrascleral fixated IOL (ISF-IOL) group. No significant differences of mean
      absolute degree of IOL tilt (2.90 +/- 0.77 vs 2.82 +/- 0.72; p = 0.633) and IOL
      decenter (151.90 +/- 59.80 vs 175.0 +/- 73.14 microns; p = 0.265) were found
      between the two groups. Post-operative LogMAR visual acuity was not statistically
      different between the two groups (0.32 +/- 0.17 vs 0.41 +/- 0.19, p = 0.089).
      Early post-operative hypotony was only present in the ISF-IOL group (13.6%).
      CONCLUSION: This study shows that DSF-IOL is as effective as ISF-IOL. This
      technique can be a simpler approach to optimize small-incision scleral fixation
      of IOL without the complications associated with intrascleral IOL fixation.

PMID- 29464489
TI  - Learning neural connectivity from firing activity: efficient algorithms with
      provable guarantees on topology.
AB  - The connectivity of a neuronal network has a major effect on its functionality
      and role. It is generally believed that the complex network structure of the
      brain provides a physiological basis for information processing. Therefore,
      identifying the network's topology has received a lot of attentions in
      neuroscience and has been the center of many research initiatives such as Human
      Connectome Project. Nevertheless, direct and invasive approaches that slice and
      observe the neural tissue have proven to be time consuming, complex and costly.
      As a result, the inverse methods that utilize firing activity of neurons in order
      to identify the (functional) connections have gained momentum recently,
      especially in light of rapid advances in recording technologies; It will soon be
      possible to simultaneously monitor the activities of tens of thousands of neurons
      in real time. While there are a number of excellent approaches that aim to
      identify the functional connections from firing activities, the scalability of
      the proposed techniques plays a major challenge in applying them on large-scale
      datasets of recorded firing activities. In exceptional cases where scalability
      has not been an issue, the theoretical performance guarantees are usually limited
      to a specific family of neurons or the type of firing activities. In this paper,
      we formulate the neural network reconstruction as an instance of a graph learning
      problem, where we observe the behavior of nodes/neurons (i.e., firing activities)
      and aim to find the links/connections. We develop a scalable learning mechanism
      and derive the conditions under which the estimated graph for a network of Leaky
      Integrate and Fire (LIf) neurons matches the true underlying synaptic
      connections. We then validate the performance of the algorithm using artificially
      generated data (for benchmarking) and real data recorded from multiple
      hippocampal areas in rats.

PMID- 29464490
TI  - Would Dedicated Emergency Surgery Professionals Improve the Emergency General
      Surgery Service and Reduce the "Weekend Effect"?

PMID- 29464491
TI  - Do I Need to Operate on That in the Middle of the Night? Development of a
      Nomogram for the Diagnosis of Severe Acute Cholecystitis.
AB  - BACKGROUND: Some authors have proposed different predictive factors of severe
      acute cholecystitis, but generally, the results of risk analyses are expressed as
      odds ratios, which makes it difficult to apply in the clinical practice of the
      acute care surgeon. The severe form of acute cholecystitis should include both
      gangrenous and phlegmonous cholecystitis, due to their severe clinical course,
      and cholecystectomy should not be delayed. The aim of this study was to create a
      nomogram to obtain a graphical tool to compute the probability of having a severe
      acute cholecystitis. METHODS: This is a retrospective study on 393 patients who
      underwent emergency cholecystectomy between January 2010 and December 2015 at the
      Acute Care Surgery Service of the S. Anna University Hospital of Ferrara, Italy.
      Patients were classified as having a non-severe acute cholecystitis or a severe
      acute cholecystitis (i.e., gangrenous and phlegmonous) based on the final
      pathology report. The baseline characteristics, pre-operative signs, and
      abdominal ultrasound (US) findings were assessed with a stepwise multivariate
      logistic regression analysis to predict the risk of severe acute cholecystitis,
      and a nomogram was created. RESULTS: Age as a continuous variable, WBC count >=
      12.4 * 103/MUl, CRP >=9.9 mg/dl, and presence of US thickening of the gallbladder
      wall were significantly associated with severe acute cholecystitis at final
      pathology report. A significant interaction between the effect of age and CRP was
      found. Four risk classes were identified based on the nomogram total points.
      CONCLUSIONS: Patients with a nomogram total point >= 74 should be considered at
      high risk of severe acute cholecystitis (at 74 total point, sensitivity = 78.5%;
      specificity = 78.2%; accuracy = 78.3%) and this finding could be useful for
      surgical planning once confirmed in a prospective study comparing the risk score
      stratification and clinical outcomes.

PMID- 29464492
TI  - Response to: Would Dedicated Emergency Surgery Professionals Improve the
      Emergency General Surgery Service and Reduce the "Weekend Effect"?

PMID- 29464495
TI  - Targeting oxidative stress, acetylcholinesterase, proinflammatory cytokine,
      dopamine and GABA by eucalyptus oil (Eucalyptus globulus) to alleviate ketamine
      induced psychosis in rats.
AB  - Essential oil of eucalyptus species is among the most common traded essential
      oils in the world. There is an increasing interest in the application of
      eucalyptus oil as a natural additive in food and pharmaceutical industry. The
      present study was undertaken to identify the phytoconstituents present in the
      essential oil of Eucalyptus globulus leaves (EO) and ascertain their protective
      effect against ketamine-induced psychosis in rats. GC-MS technique was used for
      analysis of phytoconstituents present in EO. Ketamine (50 mg/kg, i.p.) was used
      to induce psychosis in rats. Photoactometer, forced swim test and pole climb
      avoidance test were used to evaluate the protective effects of the EO (500, 1000
      and 2000 mg/kg, p.o.) on acute and chronic administration. Bar test was used to
      test the side effect of EO. Biochemical and neurochemical estimations were
      carried out to explore the possible mechanism of action. GC-MS analysis of EO
      showed the presence of a number of biologically active compounds. EO at the dose
      of 500, 1000 and 2000 mg/kg, p.o. on acute and chronic administration, decreased
      locomotor activity, immobility duration and latency to climb the pole. EO was
      effective to facilitate the release of GABA, increase GSH levels, inhibit
      dopamine neurotransmission and decrease TNF-alpha levels as well as diminish AChE
      activity in different regions of the brain. EO at the dose of 500, 1000 mg/kg did
      not produce cataleptic behavior in rats. EO at the dose of 500, 1000 mg/kg
      produced protective effects against ketamine-induced psychosis and can be further
      explored clinically against neuropsychiatric disorders.

PMID- 29464496
TI  - Tumor Targeting via Sialic Acid: [68Ga]DOTA-en-pba as a New Tool for Molecular
      Imaging of Cancer with PET.
AB  - PURPOSE: The aim of this study was to demonstrate the potential of Ga-68-labeled
      macrocycle (DOTA-en-pba) conjugated with phenylboronic vector for tumor
      recognition by positron emission tomography (PET), based on targeting of the
      overexpressed sialic acid (Sia). PROCEDURES: The imaging reporter DOTA-en-pba was
      synthesized and labeled with Ga-68 at high efficiency. Cell binding assay on Mel
      C and B16-F10 melanoma cells was used to evaluate melanin production and Sia
      overexpression to determine the best model for demonstrating the capability of
      [68Ga]DOTA-en-pba to recognize tumors. The in vivo PET imaging was done with B16
      F10 tumor-bearing SCID mice injected with [68Ga]DOTA-en-pba intravenously. Tumor,
      blood, and urine metabolites were assessed to evaluate the presence of a
      targeting agent. RESULTS: The affinity of [68Ga]DOTA-en-pba to Sia was
      demonstrated on B16-F10 melanoma cells, after the production of melanin as well
      as Sia overexpression was proved to be up to four times higher in this cell line
      compared to that in Mel-C cells. Biodistribution studies in B16-F10 tumor-bearing
      SCID mice showed blood clearance at the time points studied, while uptake in the
      tumor peaked at 60 min post-injection (6.36 +/- 2.41 % ID/g). The acquired PET
      images were in accordance with the ex vivo biodistribution results. Metabolite
      assessment on tumor, blood, and urine samples showed that [68Ga]DOTA-en-pba
      remains unmetabolized up to at least 60 min post-injection. CONCLUSIONS: Our work
      is the first attempt for in vivo imaging of cancer by targeting overexpression of
      sialic acid on cancer cells with a radiotracer in PET.

PMID- 29464497
TI  - Response to Notter and Meyer's Letter to the Editor Regarding Increased
      Expression of Translocator Protein (TSPO) Marks Pro-inflammatory Microglia but
      Does Not Predict Neurodegeneration.

PMID- 29464498
TI  - Milk Proteins Are Predigested Within the Human Mammary Gland.
AB  - Previous work demonstrates that proteases present in human milk release hundreds
      of peptides derived from milk proteins. However, the question of whether human
      milk protein digestion begins within the mammary gland remains incompletely
      answered. The primary objective of this study was to determine whether
      proteolytic degradation of human milk proteins into peptides begins within the
      mammary gland. The secondary objectives were to determine which milk proteases
      participate in the proteolysis and to predict which released peptides have
      bioactivity. Lactating mothers (n = 4) expressed their milk directly into a
      mixture of antiproteases on ice followed by immediate freezing of the milk to
      limit post-expression protease activity. Samples were analyzed for their peptide
      profiles via mass spectrometry and database searching. Peptidomics-based protease
      prediction and bioactivity prediction were each performed with several different
      approaches. The findings demonstrate that human milk contains more than 1,100
      unique peptides derived from milk protein hydrolysis within the mammary gland.
      These peptides derived from 42 milk proteins and included 306 potential bioactive
      peptides. Based on the peptidomics data, plasmin was predicted to be the milk
      protease most active in the hydrolysis of human milk proteins within the mammary
      gland. Milk proteases actively cleave milk proteins within the mammary gland,
      initiating the release of functional peptides. Thus, the directly breastfed
      infant receives partially pre-digested proteins and numerous bioactive peptides.

PMID- 29464499
TI  - Catechin Attenuates Coronary Heart Disease in a Rat Model by Inhibiting
      Inflammation.
AB  - Accumulating evidence has established that systemic inflammation is an important
      pathophysiologic factor of coronary heart disease (CHD). In this study, we
      investigated whether catechin exerts anti-inflammatory function in CHD rats. CHD
      model of rats was established by high-fat diet feeding and pituitrin injection.
      The successful building of CHD model was confirmed using blood liquid biochemical
      analyzer. Additionally, the effects of catechin on CHD parameters and several
      inflammatory signaling were investigated. The levels of total cholesterol, high
      density lipoprotein, low-density lipoprotein cholesterin, triglyceride and blood
      glucose were all significantly elevated in CHD rats compared to them in control
      rats, suggesting the successful establishment of CHD model. Administration of
      catechin attenuated CHD by reversing the levels of creatine kinase, creatine
      kinase-MB, lactate dehydrogenase, cardiac troponin (cTnT), ventricular ejection
      fraction (LVEF) and systolic internal diameter (LVIDs). Additionally, several
      inflammatory biomarkers or cytokines such as C-reactive protein, lipoprotein
      associated phospholipase A2 (Lp-PLA2), interleukin (IL)-6 and tumor necrosis
      factor-alpha (TNF-alpha) were inhibited by catechin. In contrast to nuclear
      factor-kappa beta (NF-kappaB), several proteins involved in inflammation such as
      farnesoid X receptor, signal transducers and activators of transcription (STAT)-3
      and protein kinase B (PKB/Akt) were all activated by catechin. Catechin could be
      used as a promising treatment for CHD based on its role in suppressing
      inflammation and balancing STAT-3 signaling.

PMID- 29464500
TI  - Assessment of Efficacy of BLIS-Producing Probiotic K12 for the Prevention of
      Group A Streptococcus Pharyngitis: a Short Communication.
AB  - The neutral outcome of the recently reported school-based trial of probiotic K12
      (The effect of the oral probiotic Streptococcus salivarius K12 on group A
      streptococcus pharyngitis: a pragmatic trial in schools) can be attributed at
      least partially to several readily identifiable confounding factors. Mainly, the
      execution and outcome were negatively impacted by (a) the suboptimal efficacy and
      frequency of K12 administration, (b) the failure both clinically and
      microbiologically to adequately diagnose and distinguish active group A
      streptococci (GAS) pharyngitis from harmless GAS carriage, and ( c ) the
      exceptionally low occurrence of GAS in this population at the time of the
      probiotic intervention due to recent high-intensity antibiotic exposure.

PMID- 29464501
TI  - A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and
      Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
      (CFS/ME).
AB  - Gastrointestinal (GI) symptoms and irritable bowel (IB) symptoms have been
      associated with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The
      aim of this study was to conduct a systematic review of these symptoms in CFS/ME,
      along with any evidence for probiotics as treatment. Pubmed, Scopus, Medline
      (EBSCOHost) and EMBASE databases were searched to source relevant studies for
      CFS/ME. The review included any studies examining GI symptoms, irritable bowel
      syndrome (IBS) and/or probiotic use. Studies were required to report criteria for
      CFS/ME and study design, intervention and outcome measures. Quality assessment
      was also completed to summarise the level of evidence available. A total of 3381
      publications were returned using our search terms. Twenty-five studies were
      included in the review. Randomised control trials were the predominant study type
      (n = 24). Most of the studies identified examined the effect of probiotic
      supplementation on the improvement of IB symptoms in IBS patients, or IB symptoms
      in CFS/ME patients, as well as some other significant secondary outcomes (e.g.
      quality of life, other gastrointestinal symptoms, psychological symptoms). The
      level of evidence identified for the use of probiotics in IBS was excellent in
      quality; however, the evidence available for the use of probiotic interventions
      in CFS/ME was poor and limited. There is currently insufficient evidence for the
      use of probiotics in CFS/ME patients, despite probiotic interventions being
      useful in IBS. The studies pertaining to probiotic interventions in CFS/ME
      patients were limited and of poor quality overall. Standardisation of protocols
      and methodology in these studies is required.

PMID- 29464503
TI  - The Global Music Approach to Dementia (GMA-D): evidences from a case report.

PMID- 29464502
TI  - Type 2 Diabetes Mellitus and Alzheimer's Disease: Overlapping Biologic Mechanisms
      and Environmental Risk Factors.
AB  - PURPOSE OF REVIEW: A number of studies over the past two decades have suggested
      that type 2 diabetes mellitus (T2DM) patients are at an increased risk of
      Alzheimer's disease (AD). Several common molecular pathways to cellular and
      metabolic dysfunction have been implicated in the etiology of both diseases.
      Here, we review the emerging evidence from observational studies that investigate
      the relationship between T2DM and AD, and of shared environmental risk factors,
      specifically air pollution and pesticides, associated with both chronic
      disorders. RECENT FINDINGS: Particulate matter and traffic-related air pollution
      have been widely associated with T2DM, and multiple studies have associated
      exposures with AD or cognitive function. Organochlorine (OC) and organophosphate
      (OP) pesticides have been associated with T2DM in multiple independent
      populations. Two populations have observed increased risks for OC and OP
      exposures and AD. Other studies, limited in exposure assessment, have reported
      increased risk of AD with any pesticide exposure assessments. This may suggest
      shared pathogenic pathways between environmental risk factors, T2DM, and AD.
      Research focusing on exposures related to both T2DM and AD could provide new
      disease insights on shared mechanisms and help shape innovative preventative
      measures and policy decisions.

PMID- 29464504
TI  - Significant and safe reduction of propofol sedation dose for geriatric population
      undergoing pacemaker implantation: randomized clinical trial.
AB  - OBJECTIVE: A previous multidisciplinary pilot study based on computer simulations
      for the geriatric population showed that a dose of 0.5 mg/kg/h of propofol could
      sedate patients older than 65 for pacemaker implantation. The present study
      validates that the pacemaker implantation can be done in the elderly using 0.5-1
      mg/kg/h of propofol with hemodynamic stability. METHODS: 66 patients from 65 to
      88 years old scheduled for pacemaker implantation were randomly assigned one of
      three doses of propofol. The first group received 2 mg/kg/h of propofol (P2) that
      is within normal range of the sedation dose. The second group received 1 mg/kg/h
      (P1) dose and the third group received the dose of 0.5 mg/kg/h (P0.5) according
      to the simulation-predicted dose for geriatric populations. RESULTS: All patients
      kept MAP between 76 and 85 mmHg, with no hypotension episodes in any of the
      groups; therefore, they were all hemodynamically stable during the procedure. BIS
      was between 80 and 65 during the pacemaker implantation for the three groups, BIS
      of group P2 was significantly lower than the other groups. BIS in groups P1 and
      P0.5 was within the appropriated range for moderate sedation. Brice was positive
      for auditory recalls only when there was arousing noise in the operating room.
      CONCLUSIONS: Moderate sedation, adequate for pacemaker implantation, can be
      achieved infusing 0.5-1 mg/kg/h of propofol in elderly patients when the patient
      has proper analgesia management at the device implantation site. The second
      important condition is to avoid unnecessary and alerting auditory and mechanical
      stimuli in the operating room, so that the patient will remain calm.

PMID- 29464505
TI  - Finding Time for Mindfulness: in Education, Clinical Practice, and Our Lives.

PMID- 29464507
TI  - Anomalous muscular bands of the left atrium on echocardiography.

PMID- 29464506
TI  - Idiopathic portal hypertension and extrahepatic portal venous obstruction.
AB  - BACKGROUND: Idiopathic portal hypertension (IPH) and extrahepatic portal venous
      obstruction (EHPVO) are non-cirrhotic vascular causes of portal hypertension
      (PHT). Variceal bleed and splenomegaly are the commonest presentations. AIM: The
      present review is intended to provide the existing literature on
      etiopathogenesis, clinical profile, diagnosis, natural history and management of
      IPH and EHPVO. RESULTS: IPH and EHPVO are both characterized by normal hepatic
      venous pressure gradient, moderate to massive splenomegaly with preserved liver
      synthetic functions. While the level of block in IPH is presinusoidal, in EHPVO
      it is at prehepatic level. Infections, autoimmunity, drugs, immunodeficiency and
      prothrombotic states are possible etiological agents in IPH. Contrastingly in
      EHPVO, prothrombotic disorders and local factors around the portal vein are the
      incriminating factors. Diagnosis is often clinical, supported by simple
      radiological tools. Natural history is defined by episodes of variceal bleed and
      symptoms related to enlarged spleen. Growth failure, portal biliopathy and
      minimal hepatic encephalopathy are additional concerns in EHPVO. Long-term
      survival is reasonably good with endoscopic surveillance; however, parenchymal
      extinction leading to decompensation is seen in a minority of patients in both
      the disorders. Surgical shunts revert the complications secondary to PHT. Meso
      Rex shunt has become the standard surgery in children with EHPVO. CONCLUSION:
      This review gives a detailed summary of these two vascular conditions of liver
      IPH and EHPVO. Further research is needed to understand the pathogenesis and
      natural history of these disorders.

PMID- 29464509
TI  - Agarotetrol: a source compound for low molecular weight aromatic compounds from
      agarwood heating.
AB  - Agarwood is known to generate a distinct fragrance upon heating and is used as
      both a medicine and a fragrant wood. Low molecular weight aromatic compounds
      (LACs) such as benzylacetone are emitted from agarwood on heating and have a
      sedative effect on mice. These are detected exclusively in the headspace vapor of
      heated agarwood and are absent in the wood itself; hence, some compounds in
      agarwood are thought to be converted to LACs by the process of heating. In this
      study, different fractions obtained from agarwood were analyzed to reveal the
      source compounds of LACs. Some LACs detected in the resinous agarwood were absent
      from the non-resinous parts and confirmed as characteristic of the resinous
      parts. The essential oil and hydrosol of agarwood obtained by distillation were
      analyzed by gas chromatography-mass spectrometry (GC-MS). Sesquiterpenes were
      detected in the essential oil, and sesquiterpenes and a variety of LACs were
      detected in the hydrosol. A hot water extract of agarwood remaining in the
      distillation flask after distillation was analyzed by high-performance liquid
      chromatography (HPLC), and agarotetrol was found to be the main compound.
      Purified agarotetrol was heated in a glass vial and its headspace vapor was
      analyzed by solid-phase microextraction GC-MS. Benzylacetone and other LACs were
      detected. These results indicate that agarotetrol, a chromone derivative,
      contributes to the fragrance of agarwood through the generation of LACs upon
      heating.

PMID- 29464508
TI  - Long Noncoding RNAs: New Players in the Osteogenic Differentiation of Bone Marrow
      and Adipose-Derived Mesenchymal Stem Cells.
AB  - Mesenchymal stem cells (MSCs) are an important population of multipotent stem
      cells that differentiate into multiple lineages and display great potential in
      bone regeneration and repair. Although the role of protein-coding genes in the
      osteogenic differentiation of MSCs has been extensively studied, the functions of
      noncoding RNAs in the osteogenic differentiation of MSCs are unclear. The recent
      application of next-generation sequencing to MSC transcriptomes has revealed that
      long noncoding RNAs (lncRNAs) are associated with the osteogenic differentiation
      of MSCs. LncRNAs are a class of non-coding transcripts of more than 200
      nucleotides in length. Noncoding RNAs are thought to play a key role in
      osteoblast differentiation through various regulatory mechanisms including
      chromatin modification, transcription factor binding, competent endogenous
      mechanism, and other post-transcriptional mechanisms. Here, we review the roles
      of lncRNAs in the osteogenic differentiation of bone marrow- and adipose-derived
      stem cells and provide a theoretical foundation for future research.

PMID- 29464510
TI  - Determination of (E)-ferulic acid content in the root of Angelica acutiloba: a
      simple chemical evaluation method for crude drug quality control.
AB  - The root of Angelica acutiloba Kitagawa is an important crude drug in Kampo
      medicines (traditional Japanese medicine). Chemical evaluation of crude drugs is
      crucial to ensuring the safety and efficacy of herbal medicine; however, there is
      currently no chemical standard for the A. acutiloba crude drug in Japanese
      pharmacopoeia. (E)-ferulic acid (FA) is an important active ingredient of
      Angelica spp., including A. sinensis (Oliv.) Diels, and has been suggested as a
      marker for quality evaluation of those crude drugs. However, it has been
      controversial whether FA is a reliable marker constituent of A. acutiloba. To
      achieve effective extraction of FA from A. acutiloba, we compared three different
      extraction methods: alkaline hydrolysis, ethanol extraction, and hexane
      extraction. FA levels in these extracts were assessed using high performance
      liquid chromatography (HPLC), and alkaline hydrolysis was found to be the most
      effective. Furthermore, in the hydrolysate, FA was distinctly identified by thin
      layer chromatography (TLC) analysis. These results provide useful information for
      the quality control of the A. acutiloba crude drug.

PMID- 29464511
TI  - Computational Investigation of a Self-Powered Fontan Circulation.
AB  - Children born with anatomic or functional "single ventricle" must progress
      through two or more major operations to sustain life. This management sequence
      culminates in the total cavopulmonary connection, or "Fontan" operation. A
      consequence of the "Fontan circulation", however, is elevated central venous
      pressure and inadequate ventricular preload, which contribute to continued
      morbidity. We propose a solution to these problems by increasing pulmonary blood
      flow using an "injection jet" (IJS) in which the source of blood flow and energy
      is the ventricle itself. The IJS has the unique property of lowering venous
      pressure while enhancing pulmonary blood flow and ventricular preload. We report
      preliminary results of an analysis of this circulation using a tightly-coupled,
      multi-scale computational fluid dynamics model. Our calculations show that,
      constraining the excess volume load to the ventricle at 50% (pulmonary to
      systemic flow ratio of 1.5), an optimally configured IJS can lower venous
      pressure by 3 mmHg while increasing systemic oxygen delivery. Even this small
      decrease in venous pressure may have substantial clinical impact on the Fontan
      patient. These findings support the potential for a straightforward surgical
      modification to decrease venous pressure, and perhaps improve clinical outcome in
      selected patients.

PMID- 29464512
TI  - Feasibility of continuous sedation monitoring in critically ill intensive care
      unit patients using the NeuroSENSE WAVCNS index.
AB  - Sedation in the intensive care unit (ICU) is challenging, as both over- and under
      sedation are detrimental. Current methods of assessment, such as the Richmond
      Agitation Sedation Scale (RASS), are measured intermittently and rely on
      patients' behavioral response to stimulation, which may interrupt sleep/rest. A
      non-stimulating method for continuous sedation monitoring may be beneficial and
      allow more frequent assessment. Processed electroencephalography (EEG) monitors
      have not been routinely adopted in the ICU. The aim of this observational study
      was to assess the feasibility of using the NeuroSENSETM monitor for EEG-based
      continuous sedation assessment. With ethical approval, ICU patients on continuous
      propofol sedation were recruited. Depth-of-hypnosis index (WAVCNS) values were
      obtained from the NeuroSENSE. Bedside nurses, blinded to the NeuroSENSE,
      performed regular RASS assessments and maintained the sedation regimen as per
      standard of care. Participants were monitored throughout the duration of their
      propofol infusion, up to 24 h. Fifteen patients, with median [interquartile
      range] age of 57 [52-62.5] years were each monitored for a duration of 9.0 [5.7
      20.1] h. Valid WAVCNS values were obtained for 89% [66-99] of monitoring time and
      were widely distributed within and between individuals, with 6% [1-31] spent < 40
      (very deep), and 3% [1-15] spent > 90 (awake). Significant EEG suppression was
      detected in 3/15 (20%) participants. Observed RASS matched RASS goals in 36/89
      (40%) assessments. The WAVCNS variability, and incidence of EEG suppression,
      highlight the limitations of using RASS as a standalone sedation measure, and
      suggests potential benefit of adjunct continuous brain monitoring.

PMID- 29464513
TI  - Lipids in RA: Is Less Not Necessarily More?
AB  - PURPOSE OF REVIEW: In rheumatoid arthritis (RA), lipid levels are dynamic and can
      fluctuate along with changes in inflammation. A reduction in inflammation, most
      commonly as a result of disease-modifying anti-rheumatic drug (DMARD) therapy, is
      associated with increases in total cholesterol (TC) and low-density lipoprotein
      cholesterol (LDL-C). In this review, we discuss new evidence shedding light on
      the potential mechanism underlying changes in lipid levels observed with changes
      in inflammation. RECENT FINDINGS: Measured lipid levels in the blood are a result
      of a balance between synthesis and catabolism or absorption. Recent human studies
      in active RA show that the catabolic rates of lipids are higher than expected
      compared to expected rates in the general population. DMARD therapy appears to
      allow a return to baseline lower catabolic rates, resulting in an apparent
      increase in lipids. Increases in lipids observed with control of inflammation and
      RA treatment suggest a return to homeostasis. Studies are underway to understand
      the overall impact on cardiovascular risk in RA when lipid levels increase as a
      result of controlling inflammation.

PMID- 29464514
TI  - Correction to: Peripheral Th17/Treg imbalance in elderly patients with ischemic
      stroke.
AB  - In the original article the terms RORgammat and GF-beta were misspelled
      throughout the text. They should read RORgammat and TGF-beta instead. We
      apologize for the inconvenience. The original article has been corrected.

PMID- 29464515
TI  - Preoperative breast MRI: reproducibility and significance of findings relevant to
      nipple-areolar complex involvement.
AB  - BACKGROUND: Eligibility of nipple-sparing mastectomy has been expanded. The
      purpose of this study was to evaluate interobserver agreement regarding magnetic
      resonance imaging (MRI) descriptors important in determining eligibility for
      mastectomy, and to investigate the significance of enhancement extending to the
      areola concerning nipple-areolar complex (NAC) involvement. METHODS: Fifty-one
      cases with histologically confirmed NAC involvement and 54 cases with negative
      NAC were enrolled. Two radiologists assessed the following factors: lesion
      morphology (mass or non-mass enhancement); intra-nipple bright signal;
      enhancement extending to the areola; abnormal nipple enhancement; and tumor
      nipple distance. Factors that showed a significant association with outcome in
      the univariate analysis were assessed by means of multivariate analysis using a
      logistic regression model. Interobserver agreement between observers was assessed
      by calculating kappa values (dichotomous variables), or intraclass correlation
      coefficients (ICCs; continuous variables). RESULTS: In multivariate analysis of
      the results from the two observers, tumor-nipple distance (observer 1: odds ratio
      [OR] 0.93; 95% confidence interval [CI] 0.88-0.99; observer 2: OR 0.89; 95% CI
      0.83-0.95) and enhancement extending to the areola (observer 1: OR 17.9; 95% CI
      1.97-162.2; observer 2: OR 24.0; 95% CI 2.62-219.7) were found to be significant
      predictors of NAC involvement. A substantial agreement (kappa = 0.64-0.71) for
      every dichotomous variable and an almost perfect agreement (ICC = 0.86) for
      continuous variable were observed. CONCLUSIONS: Findings of breast MRI for NAC
      preservation had good interobserver agreement. Enhancement extending to the
      areola, together with tumor-nipple distance, was significant factors for NAC
      involvement.

PMID- 29464517
TI  - Evaluation of Kefir as a New Anodic Biocatalyst Consortium for Microbial Fuel
      Cell.
AB  - Kefir, a combined consortium of bacteria and yeast encapsulated by a polymeric
      matrix of exopolysaccharides, was used as anodic biocatalyst in a two-chamber
      microbial fuel cell (MFC). Fermentation was followed during 72 h and polarization
      curves were obtained from linear sweep voltammetry. The effect of methylene blue
      as charge-transfer mediator in the kefir metabolism was evaluated. UV/Vis
      spectrophotometry and cyclic voltammetry were applied to evaluate the redox state
      of the mediator and to characterize the electrochemical activity, whereas current
      interruption was used for internal resistance determination. Aiming to establish
      a relationship between the microbial development inside the anodic chamber with
      the generated power in the MFC, total titratable acidity, pH, viscosity,
      carbohydrate assimilation, and microbial counting were assayed. The kefir-based
      MFC demonstrated a maximum power density of 54 mW m-2 after 24 h fermentation,
      revealing the potential use of kefir as a biocatalyst for microbial fuel cells.

PMID- 29464518
TI  - ERP Source Analysis Guided by fMRI During Familiar Face Processing.
AB  - Event related potentials (ERPs) provide precise temporal information about
      cognitive processing, but with poor spatial resolution, while functional magnetic
      resonance imaging (fMRI) reliably identifies brain areas involved, but with poor
      temporal resolution. Here we use fMRI to guide source localization of the ERPs at
      different times for studying the temporal dynamics of the neural system for
      recognizing familiar faces. fMRI activation areas were defined in a previous
      experiment applying the same paradigm used for ERPs. The Bayesian model averaging
      (BMA) method was used to estimate the generators of the ERPs to unfamiliar,
      visually familiar, and personally-familiar faces constraining the model by fMRI
      activation results. For this, higher prior probabilities in the solution space
      were assigned to the fMRI-defined regions, which included face-selective areas
      and other areas related to "person knowledge" retrieval. Source analysis was
      carried out in three-time windows: early (150-210 ms), middle (300-380 ms) and
      late (460-580 ms). The early and middle responses were generated in fMRI-defined
      areas for all face categories, while these areas do not contribute to the late
      response. Different areas contributed to the generation of the early and middle
      ERPs elicited by unfamiliar faces: fusiform (Fus), inferior occipital, superior
      temporal sulcus and the posterior cingulate (PC) cortices. For familiar faces,
      the contributing areas were Fus, PC and anterior temporal areas for visually
      familiar faces, with the addition of the medial orbitofrontal areas and other
      frontal structures for personally-significant faces. For both unfamiliar and
      familiar faces, more extended and reliable involvement of contributing areas were
      obtained for the middle compare with early time window. Our fMRI guide ERP source
      analysis suggested the recruitment of person-knowledge processing areas as early
      as 150-210 ms after stimulus onset during recognition of personally-familiar
      faces. We concluded that fMRI-constrained BMA source analysis provide information
      regarding the temporal-dynamics in the neural system for cognitive processsing.

PMID- 29464516
TI  - Quantitative Comparison of Primary Cilia Marker Expression and Length in the
      Mouse Brain.
AB  - Primary cilia are small, special cellular organelles that provide important
      sensory and signaling functions during the development of mammalian organs and
      coordination of postnatal cellular processes. Dysfunction of primary cilia are
      thought to be the main cause of ciliopathies, a group of genetic disorders
      characterized by overlapping developmental defects and prominent
      neurodevelopmental features. Although, disrupted cilia-linked signaling pathways
      have been implicated in the regulation of numerous neuronal functions, the
      precise role of primary cilia in the brain are still unknown. Importantly,
      studies of recent years have highlighted that different functions of primary
      cilia are reflected by their diverse morphology and unique signaling components
      localized in the ciliary membrane. In the present study, we conducted a
      comparative analysis of the expression pattern, distribution and length of
      adenylyl cyclase 3, somatostatin receptor 3, and ADP-ribosylation factor-like
      protein 13B expressing primary cilia in the mouse brain. We show that cilia of
      neurons and astrocytes display a well characterized distribution and ciliary
      marker arrangements. Moreover, quantitative comparison of their length, density
      and occurrence rate revealed that primary cilia exhibit region-specific
      alternations. In summary, our study provides a comprehensive overview of the
      cellular organization and morphological traits of primary cilia in regions of the
      physiological adult mouse brain.

PMID- 29464520
TI  - Infrared Spectroscopy and Imaging in Stem Cells and Aging Research.
AB  - The effect of aging process on stem cell function is crucial because of their
      critical role in tissue regeneration and repair. The impact of aging on stem
      cells needs to be understood clearly for the success of clinical application and
      obtaining desired therapeutic outcome throughout the novel stem cell based
      therapies. The existing methods used to monitor and characterize the stem cells
      have some unwanted effects on the properties of stem cells and these methods also
      do not provide real-time information about cellular conditions. These challenges
      enforce the usage of nondestructive, rapid, sensitive, high-quality, label-free,
      cheep, and innovative chemical monitoring methods. In this context, vibrational
      spectroscopy provides promising alternative to get new information into the field
      of stem cell biology for chemical analysis, quantification, and imaging of stem
      cells. Infrared spectroscopy and imaging coupled with chemometric methods can be
      used as novel and complimentary methods to obtain new insight into stem cell
      studies for future therapeutic and regenerative medicine.

PMID- 29464519
TI  - MRI Verification of a 10-20 Targeting Protocol Used During Transcranial Magnetic
      Stimulation Sessions for Tinnitus.
AB  - Langguth et al. (2006) described a method for targeting primary auditory cortex
      (PAC) during transcranial magnetic stimulation (TMS) using the 10-20
      electroencephalography system. Study aims were to measure the degree of accuracy
      in placing the TMS coil on the scalp overlying PAC using the 10-20 method and
      determine the extent to which accuracy depends on the hemisphere of the coil
      placement. Twelve participants underwent anatomical magnetic resonance imaging
      (MRI) of their head in a 3T scanner. Before imaging, a fiducial marker was placed
      on their scalp corresponding to the TMS coil position. MRI scans were analyzed to
      determine the distance from the fiducial marker to PAC for each participant. On
      average, the 10-20 method resulted in distances in the medial-lateral, anterior
      posterior, and inferior-superior dimensions that were within a few millimeters (~
      4 mm) of each other between the left and right hemispheres. The fiducial marker
      was, on average, 10.4 mm superior and 10.8 mm posterior to the optimal scalp
      location that minimized the distance to PAC. Individual asymmetries and other
      systematic differences found in this study raise important considerations to keep
      in mind that might necessitate using an MRI-guided method of coil-positioning
      when targeting PAC for TMS.

PMID- 29464521
TI  - Remembering the place with the tiger: Survival processing can enhance source
      memory.
AB  - Rating the relevance of words for survival in the grasslands of a foreign land
      often leads to a memory advantage. However, it is as yet unclear whether the
      survival processing effect generalizes to source memory. Here, we examined
      whether people have enhanced source memory for the survival context in which an
      item has been encountered. Participants were asked to make survival-based or
      moving-based decisions about items prior to a classical source memory test. A
      multinomial model was used to measure old-new discrimination, source memory, and
      guessing biases separately. We replicated the finding of a survival advantage in
      old-new recognition. Extending previous results, we also found a survival
      processing advantage in source memory. These results are in line with the
      richness-of-encoding explanation of the survival processing advantage and with an
      adaptive perspective on memory.

PMID- 29464522
TI  - Protective effects of a modified apelin-12 and dinitrosyl iron complexes in
      experimental cardioplegic ischemia and reperfusion.
AB  - The maintenance of nitric oxide (NO) bioavailability has been recognized as an
      important component of myocardial protection during cardiac surgery. This study
      was designed to evaluate the efficacy of using two NO-donating compounds in
      cardioplegia and reperfusion: (i) a modified peptide apelin-12 (MA12) that
      activates endothelial NO synthase (eNOS) and (ii) dinitrosyl iron complexes with
      reduced glutathione (DNIC-GS), a natural NO vehicle. Isolated perfused working
      rat hearts were subjected to normothermic global ischemia and reperfusion. St.
      Thomas' Hospital cardioplegic solution (STH) containing 140 MUM MA12 or 100 MUM
      DNIC-GS was used. In separate series, 140 MUM MA12 or 100 MUM DNIC-GS was
      administered at early reperfusion. Metabolic state of the hearts was evaluated by
      myocardial content of high-energy phosphates and lactate. Lactate dehydrogenase
      (LDH) activity in myocardial effluent was used as an index of cell membrane
      damage. Cardioplegia with MA12 or DNIC-GS improved recovery of coronary flow and
      cardiac function, and reduced LDH leakage in perfusate compared with STH without
      additives. Cardioplegic arrest with MA12 significantly enhanced preservation of
      high-energy phosphates and decreased accumulation of lactate in reperfused
      hearts. The overall protective effect of cardioplegia with MA12 was significantly
      greater than with DNIC-GS. The administration of MA12 or DNIC-GS at early
      reperfusion also increased metabolic and functional recovery of reperfused
      hearts. In this case, recovery of cardiac contractile and pump function indices
      was significantly higher if reperfusion was performed with DNIC-GS. The results
      show that MA12 and DNIC-GS are promising adjunct agents for protection of the
      heart during cardioplegic arrest and reperfusion.

PMID- 29464523
TI  - Methotrexate preferentially affects Tc1 and Tc17 subset of CD8 T lymphocytes.
AB  - Rheumatoid arthritis is considered a T-lymphocyte-mediated disease. However,
      studies have focussed on CD4 T-lymphocytes, ignoring CD8 T-lymphocytes despite
      the latter being found abundantly in the synovium. Specifically, there is little
      data of the effect of methotrexate, the gold-standard DMARD, on various CD8
      cytokine T-lymphocyte subsets and conflicting data on CD4 subsets. In this
      prospective study, patients with active rheumatoid arthritis, who were 18 to 65
      years of age, were treated with methotrexate (up to 25 mg per week) for 24 weeks.
      At baseline and 24 weeks, frequencies of CD8+IFNgamma+, CD8+IL17+, CD8+IL4+,
      corresponding CD4 subsets and plasma levels of IFNgamma, IL-12, IL-10, IL-4 and
      IL-17 were determined by flow cytometry. These are summarised as median (IQR =
      interquartile range, 25th-75th percentile) and paired data compared using
      Wilcoxon signed rank test. This study included 67 patients (F/M = 4:1) with
      rheumatoid arthritis, 57 (85%) being RF positive and 20 receiving prednisolone at
      baseline. Mean (+/- SD) dose of methotrexate at 24 weeks was 22.9 +/- 3.0 mg per
      week. On treatment with methotrexate, there was a significant (p = 0.04) decline
      in CD8+IFNgamma+ cells from 37.2 (IQR 19.4-60.2) to 22.7% (IQR 8.5-49.7) and a
      marginal increase in CD8+IL17+ cells from 0.3 (IQR 0.1-0.6) to 0.4 (IQR 0.2-1.2),
      p = 0.006. There was no significant change in the other subsets. There was also a
      significant decline in circulating levels of IL-12, IL-10 and IL-17 and marginal
      increase in IL-4. On evaluating by response, non-responders but not responders
      had a significant increase in CD8+IL17+ (p = 0.01). There is a significant
      decline of CD8+IFNgamma+ T cells and marginal increase in CD8+IL17+ T cells after
      methotrexate. Change in Tc1 subset may be mediated through reduction in IL-12
      levels.

PMID- 29464524
TI  - Physical articular examination in the activity of rheumatoid arthritis: a
      systematic review of the literature : Systematic review of the literature
      regarding physical examination in rheumatoid arthritis.
AB  - To summarize evidence concerning the articular examination needed to determine
      rheumatoid arthritis (RA) activity (follow-up or control) via a systematic
      review. A search of Medline, Embase, Lilacs, SciELO, the Web of Science, the
      National Technical Reports Library, and the reference lists of relevant studies
      through March 2017 was conducted using a systematic methodology to identify
      studies of patients with RA older than 18 years in which a detailed description
      of the physical examination or a description of the components of the articular
      examination was provided. Of 8322 references, 74 studies were included according
      to the selection criteria, and 6 references were ultimately included at the end
      of the review. Most of the included studies (n = 5) were associated with a
      moderate risk of bias. There was great variability among the studies and the
      articular examination methods used. Some studies presented the examination with a
      complete specification of the technique (n = 2), the consensus of rheumatologists
      (n = 2), or training through audiovisual materials and face-to-face courses (n =
      2), but none of the studies explicitly showed the technique by which the physical
      examination was performed. Despite the importance of the clinical evaluation and
      physical examination of patients with RA for diagnosis, prognosis, clinimetrics,
      and follow-up, evidence concerning how to perform the articular examination is
      scarce.

PMID- 29464525
TI  - Correction to: Drug survival and effectiveness of ustekinumab in patients with
      psoriatic arthritis. Real-life data from the biologic Apulian registry (BIOPURE).
AB  - In Fig. 1 - paned D, incorrect image was published. This is now presented
      correctly in this article.

PMID- 29464526
TI  - Characteristics of children with acute lymphoblastic leukemia presenting with
      arthropathy.
AB  - Acute lymphoblastic leukemia (ALL) is the most common childhood neoplasia and may
      present with arthralgia and arthritis, with the risk of misdiagnosis and
      diagnostic delay. We describe in detail arthropathy (arthritis/arthralgia) among
      children with leukemia as the children's laboratory results, misdiagnosis, and
      treatment before the diagnosis of ALL and the diagnostic delay. In this
      retrospective cohort study, we reviewed records of 286 children aged 1-15 years
      diagnosed with ALL from January 1992 to March 2013. We identified 26 children
      with arthralgia and 27 children with arthritis. The majority of the children had
      one or two joints involved (arthralgia 72%, arthritis 42%), and most often hips
      and knees. Morning stiffness was not reported. Imaging of affected joints was
      included in the initial workup of 77% of children with ALL and arthropathy, and
      66% was abnormal. Misdiagnosis as JIA occurred in 26% and 71% of these children
      received treatment with intraarticular corticosteroids. The diagnostic delay was
      3 weeks longer for the children with arthritis than those with arthralgia (median
      54 vs 36 days), primarily as a consequence of a longer first doctor's delay.
      Compared to the children with arthralgia, the children with arthritis were more
      often misdiagnosed and treated with intraarticular steroid before the diagnosis
      of ALL. They also had longer diagnostic delay, primarily as a consequence of a
      longer first doctor's delay.

PMID- 29464528
TI  - The shaded side of the UHC cube: a systematic review of human resources for
      health management and administration in social health protection schemes.
AB  - Managers and administrators in charge of social protection and health financing,
      service purchasing and provision play a crucial role in harnessing the potential
      advantage of prudent organization, management and purchasing of health services,
      thereby supporting the attainment of Universal Health Coverage. However, very
      little is known about the needed quantity and quality of such staff, in
      particular when it comes to those institutions managing mandatory health
      insurance schemes and purchasing services. As many health care systems in low-
      and middle-income countries move towards independent institutions (both
      purchasers and providers) there is a clear need to have good data on staff and
      administrative cost in different social health protection schemes as a basis for
      investing in the development of a cadre of health managers and administrators for
      such schemes. We report on a systematic literature review of human resources in
      health management and administration in social protection schemes and suggest
      some aspects in moving research, practical applications and the policy debate
      forward.

PMID- 29464529
TI  - Prognostic Factors and the Role of Adjuvant Treatment in Periampullary Carcinoma:
      a Single-Centre Experience of 95 Patients.
AB  - PURPOSE: The effect of adjuvant treatment on those undergoing
      pancreaticoduodenectomy (PD) for periampullary carcinomas (PAC) is not well
      studied. Most studies employed chemoradiation as the adjuvant modality. We aimed
      to analyse clinicopathological differences between types of PACs, the prognostic
      factors and the role of adjuvant therapy (chemotherapy in the majority). METHODS:
      Patients with PAC who underwent PD from Jan 2011 to Dec 2015 were retrospectively
      analysed. RESULTS: Ninety-five patients with PAC underwent PD in the study
      period. Ampullary carcinoma (AC) was the most common. Pancreatic carcinomas (PC)
      were larger. AC had lower T stage, perineural invasion (PNI) and R1 resections.
      Median overall survival (OS) was 32.7 months. On multivariate analysis, lymph
      node ratio (LNR) >= 0.2 and advanced T stage adversely affected the OS. Fifty
      seven (66.3%) patients received adjuvant treatment, of which 50 had chemotherapy
      alone. Adjuvant treatment resulted in better OS in patients with T stage >= 3,
      lymph node involvement, LNR >= 0.2, lymphovascular invasion, PNI, tumour size > 2
      cm, higher grade and distal cholangiocarcinoma. CONCLUSION: In patients of PAC
      undergoing PD, AC had favourable clinicopathological profile. LNR >= 0.2 and
      advanced T stage adversely affected OS. Adjuvant treatment resulted in
      significantly better OS in patients with high-risk features.

PMID- 29464527
TI  - What we do and do not know about women and kidney diseases; questions unanswered
      and answers unquestioned: reflection on World Kidney Day and International
      Women's Day.
AB  - Chronic Kidney Disease affects approximately 10% of the world's adult population:
      it is within the top 20 causes of death worldwide, and its impact on patients and
      their families can be devastating. World Kidney Day and International Women's Day
      in 2018 coincide, thus offering an opportunity to reflect on the importance of
      women's health and specifically their kidney health, on the community, and the
      next generations, as well as to strive to be more curious about the unique
      aspects of kidney disease in women so that we may apply those learnings more
      broadly. Girls and women, who make up approximately 50% of the world's
      population, are important contributors to society and their families. Gender
      differences continue to exist around the world in access to education, medical
      care, and participation in clinical studies. Pregnancy is a unique state for
      women, offering an opportunity for diagnosis of kidney disease, but also a state
      where acute and chronic kidney diseases may manifest, and which may impact future
      generations with respect to kidney health. There are various autoimmune and other
      conditions that are more likely to impact women with profound consequences for
      child bearing, and on the fetus. Women have different complications on dialysis
      than men, and are more likely to be donors than recipients of kidney transplants.
      In this editorial, we focus on what we do and do not know about women, kidney
      health, and kidney disease, and what we might learn in the future to improve
      outcomes worldwide.

PMID- 29464530
TI  - Difference in regional neural fluctuations and functional connectivity in Crohn's
      disease: a resting-state functional MRI study.
AB  - Patients with Crohn's disease (CD) are shown to have abnormal changes in brain
      structures. This study aimed to further investigate whether these patients have
      abnormal brain activities and network connectivity. Sixty patients with CD and 40
      healthy controls (HCs) underwent resting-state functional magnetic resonance
      imaging (fMRI) scans. Amplitude of low-frequency fluctuation (ALFF) and seed
      based functional connectivity (FC) were used to assess differences in spontaneous
      regional brain activity and functional connectivity. Compared to the HCs,
      patients with CD showed significantly higher ALFF values in hippocampus and
      parahippocampus (HIPP/paraHIPP), anterior cingulate cortex, insula, superior
      frontal cortex and precuneus. The ALFF values were significantly lower in
      secondary somatosensory cortex (S2), precentral gyrus, and medial prefrontal
      cortex. Functional connectivities between left HIPP and left inferior temporal
      cortex, and right middle cingulate cortex, HIPP, and fusiform area were
      significantly lower. The functional connectivities between right HIPP and right
      inferior orbitofrontal cortex and left HIPP were also significantly lower.
      Patients with CD showed higher or lower spontaneous activity in multiple brain
      regions. Altered activities in these brain regions may collectively reflect
      abnormal function and regulation of visceral pain and sensation, external
      environmental monitoring, and cognitive processing in these patients. Lower
      functional connectivity of the hippocampus-limbic system was observed in these
      patients. These findings may provide more information to elucidate the
      neurobiological mechanisms of the disease.

PMID- 29464531
TI  - The relationship between voxel-based metrics of resting state functional
      connectivity and cognitive performance in cognitively healthy elderly adults.
AB  - In previous studies, resting-state functional connectivity (FC) metrics of
      specific brain regions or networks based on prior hypotheses have been correlated
      with cognitive performance. Without constraining our analyses to specific regions
      or networks, we employed whole-brain voxel-based weighted degree (WD), a measure
      of local FC strength, to be correlated with three commonly used
      neuropsychological assessments of language, executive function and memory
      retrieval in both positive and negative directions in 67 cognitively healthy
      elderly adults. We also divided voxel-based WD into short-ranged and long-ranged
      WDs to evaluate the influence of FC distance on the WD-cognition relationship,
      and performed three validation tests. Our results showed that for language and
      executive function tests, positive WD correlates were located in the frontal and
      temporal cortices, and negative WD correlates in the precuneus and occipital
      cortices; for memory retrieval, positive WD correlates were located in the
      inferior temporal cortices, and negative WD correlates in the anterior cingulate
      cortices and supplementary motor areas. An FC-distance-dependent effect was also
      observed, with the short-ranged WD correlates of language and executive function
      tests located in the medial brain regions and the long-ranged WD correlates in
      the lateral regions. Our findings suggest that inter-individual differences in FC
      at rest are predictive of cognitive ability in the elderly adults. Moreover, the
      distinct patterns of positive and negative WD correlates of cognitive performance
      recapitulate the dichotomy between task-activated and task-deactivated neural
      systems, implying that a competition between distinct neural systems on
      functional network topology may have cognitive relevance.

PMID- 29464532
TI  - Contaminant exposure effects in a changing climate: how multiple stressors can
      multiply exposure effects in the amphipod Hyalella azteca.
AB  - Global climate change (GCC) is likely to intensify the synergistic effects
      between altered physicochemical parameters [of changing habitats] and other
      anthropogenic threats, such as water pollution, posing increased risks to aquatic
      biodiversity. As such, it is critical to understand how organisms will respond to
      changes in water temperature and salinity in the presence of contaminants. We
      exposed the epibenthic amphipod Hyalella azteca to a 3 * 3 factorial treatment
      design of three temperatures and three salinities ranging from 12 to 18  degrees
      C and 0 to 8 parts per thousand (ppt), respectively, in combination with a low
      level environmentally relevant concentration of the pyrethroid insecticide
      bifenthrin (1 ng/L). Effects on survival and swimming behavior were evaluated
      after 96 h exposure. Transcription of a select suite of genes was monitored at
      24, 48, and 96 h using quantitative polymerase chain reaction (qPCR). Our results
      not only demonstrate that the changes in salinity and temperature result in
      negative effects to invertebrate survival, behavior, and gene response, but that
      the effects were significantly more pronounced in the presence of bifenthrin.
      This is particularly important since greater thermal fluctuations, changes in
      timing and extent of glacial melt, and changes in precipitation, could result in
      H. azteca experiencing lower temperatures at times that coincide with increased
      spraying of pyrethroids. These environmentally relevant exposures using the
      standard test species H. azteca provide essential information for understanding
      effects caused by GCC in conjunction with increasing pesticide use, further
      highlighting the need to incorporate GCC impacts into risk assessments of
      contaminants of concern.

PMID- 29464533
TI  - Photo-induced toxicity in early life stage fiddler crab (Uca longisignalis)
      following exposure to Deepwater Horizon oil.
AB  - The 2010 explosion of the Deepwater Horizon (DWH) oil rig led to the release of
      millions of barrels of oil in the Gulf of Mexico. Oil in aquatic ecosystems
      exerts toxicity through multiple mechanisms, including photo-induced toxicity
      following co-exposure with UV radiation. The timing and location of the spill
      coincided with both fiddler crab reproduction and peak yearly UV intensities,
      putting early life stage fiddler crabs at risk of injury due to photo-induced
      toxicity. The present study assessed sensitivity of fiddler crab larvae to photo
      induced toxicity during co-exposure to a range of environmentally relevant
      dilutions of high-energy water accommodated fractions of DWH oil, and either <10,
      50, or 100% ambient sunlight, achieved with filters that allowed for variable UV
      penetration. Solar exposures (duration: 7-h per day) were conducted for two
      consecutive days, with a dark recovery period (duration: 17-h) in between.
      Survival was significantly decreased in treatments the presence of >10% UV and
      relatively low concentrations of oil. Results of the present study indicate
      fiddler crab larvae are sensitive to photo-induced toxicity in the presence of
      DWH oil. These results are of concern, as fiddler crabs play an important role as
      ecosystem engineers, modulating sediment biogeochemical processes via burrowing
      action. Furthermore, they occupy an important place in the food web in the Gulf
      of Mexico.

PMID- 29464534
TI  - A hedgehog pathway-dependent gene signature is associated with poor clinical
      outcomes in Luminal A breast cancer.
AB  - PURPOSE: High expression of glioma-associated oncogene homolog-1 (GLI1) is
      associated with poor prognosis in estrogen receptor (ER) positive breast cancers.
      We sought to define a GLI1-dependent gene signature in ER-positive tumors that
      could further stratify patients at higher risk for disease recurrence and
      potentially lead to novel combination therapies. METHODS: We identified an
      inverse correlation between GLI1 expression and distant disease-free survival
      (DFS) using a dataset developed at MD Anderson Cancer Center (Hatzis dataset)
      containing clinical data from 508 breast cancer patients. Using a qPCR-based
      microarray platform, we identified genes differentially regulated by GLI1 in MCF7
      cells and then determined if expression of these genes correlated with GLI1
      expression in patient tumor samples. Statistical comparison between the groups
      was performed by ANOVA. Direct comparison of two groups was done by a two-tailed
      t test. Correlations between variables were done by Pearson's method. RESULTS:
      Expression of GLI1 and its target genes correlated significantly with worse
      distant DFS in breast cancer patients with Luminal A molecular subtype.
      Particularly, co-expression of GLI1 with EGFR and/or SNAI1, two of the identified
      GLI1 targets, was predictive of worse distant DFS in this subtype. Furthermore,
      patients with Luminal A tumors with a high GLI1 signature had a shorter distant
      DFS compared to the Luminal B subtype and the outcome for this group was
      comparable to patients with HER2-positive or basal-like tumors. CONCLUSION: We
      have identified a novel GLI1 gene signature that is associated with worse
      clinical outcomes among the patients with Luminal A subtype of breast cancer.

PMID- 29464535
TI  - Long-term survival and cure model following liver resection for breast cancer
      metastases.
AB  - INTRODUCTION: Long-term survival is still rarely achieved with current systemic
      treatment in patients with breast cancer liver metastases (BCLM). Extended
      survival after hepatectomy was examined in a select group of BCLM patients.
      PATIENTS AND METHODS: Hepatectomy for BCLM was performed in 139 consecutive
      patients between 1985 and 2012. Patients who survived < 5 years were compared to
      those who survived >= 5 years from first diagnosis of hepatic metastases.
      Predictive factors for survival were analyzed. Statistically cured, defined as
      those patients who their hazard rate returned to that of the general population,
      was analyzed. RESULTS: Of the 139, 43 patients survived >= 5 years. Significant
      differences between patient groups (< 5 vs. >= 5 years) were mean time interval
      between primary tumor and hepatic metastases diagnosis (50 vs. 43 months), mean
      number of resected tumors (3 vs. 2), positive estrogen receptors (54% vs. 79%),
      microscopic lymphatic invasion (65% vs. 34%), vascular invasion (63% vs. 37%),
      hormonal therapy after resection (34% vs. 74%), number of recurrence (40% vs.
      65%) and repeat hepatectomy (1% vs. 42%), respectively. The probability of
      statistical cure was 14% (95% CI 1.4-26.7%) in these patients. CONCLUSIONS:
      Hepatectomy combined with systemic treatment can provide a chance of long-term
      survival and even cure in selected patients with BCLM. Microscopic
      vascular/lymphatic invasion appears to be a novel predictor for long-term
      survival after hepatectomy for BCLM and should be part of the review when
      discussing multidisciplinary treatment strategies.

PMID- 29464536
TI  - A Specialized Medical Management Program to Address Post-operative Weight Regain
      in Bariatric Patients.
AB  - INTRODUCTION: Although bariatric surgery results in massive weight loss, weight
      regain over time up to as much as 25% is not uncommon. Weight regain in this
      population often leads to long-term weight loss failure and non-compliance in
      clinical follow-up and program recommendations. METHODS: We analyzed early weight
      outcomes at 3 and 6 months of 48 bariatric patients referred to an
      individualized, multidisciplinary medical management program at the Center for
      Obesity Medicine (COM) to address weight regain in 2015 and compared to a group
      of matched non-bariatric patients. The medical management center, under the
      direction of a medical obesity specialist and complementary to the surgical
      program and multidisciplinary team, addressed weight regain with intensive
      lifestyle (diet, activity, anti-stress therapy, behavioral counseling, sleep) and
      with medical intervention (one or more anti-obesity medications). RESULTS:
      According to early findings, the average percentage post-operative weight regain
      of patients entering the weight management program was 20% above nadir and time
      since surgery averaged 6 years (range = 1 to 20 years) with a mean weight loss of
      - 2.3 kg after 3 months and - 4.4 kg at 6 months into the program. Individuals
      most successful with weight loss were those treated with anorexigenic
      pharmaceuticals. Weight and percent weight loss were significantly greater for
      the non-surgical than the surgical patients at 3 and 6 months (p < 0.05).
      CONCLUSIONS: A medically supervised weight management program complementary to
      surgery is beneficial for the treatment of weight regain and may prove important
      in assisting the surgical patient achieve long-term weight loss success.

PMID- 29464537
TI  - Correction to: Recommendations from Two Citizens' Juries on the Surgical
      Management of Obesity.
AB  - The spelling of the name of author K. Chalkidou was incorrect in the original
      article. It is correct here.

PMID- 29464538
TI  - Temperament Moderators of Prospective Associations Between Community Violence
      Exposure and Urban African American Adolescents' Aggressive Behavior.
AB  - Research suggests that neighborhood risks are associated with internalizing
      symptoms for adolescents high on temperament characteristics related to the
      behavioral inhibition system (BIS). However, it is unclear whether newer
      conceptualizations of the BIS distinguishing fear from anxiety operate similarly.
      Furthermore, it is unclear whether the BIS attenuates community violence exposure
      effects on externalizing problems. The current study examined whether the BIS or
      the fight-flight-freeze system (FFFS) moderated associations between community
      violence exposure and internalizing and externalizing problems. Participants were
      367 urban African American adolescents who reported on temperament
      characteristics in grade 9, and community violence exposure and adjustment
      problems in grades 9 and 10. Hierarchical linear regression analyses indicated
      that the FFFS, but not the BIS, moderated the association between community
      violence exposure and aggressive behavior. Grade 9 community violence exposure
      was positively associated with grade 10 aggression for adolescents low on FFFS,
      suggesting that the FFFS may partly differentiate community violence-exposed
      adolescents' aggressive behavior.

PMID- 29464539
TI  - Use of discriminant analysis for the evaluation of coccidiosis resistance
      parameters in chickens raised in hot humid tropical environment.
AB  - Coccidiosis endemicity remains a major challenge in poultry production in the
      tropics and all over the world. In order to develop predictive tool for
      identification of chickens that are at risk of coccidiosis among Nigerian
      indigenous chickens, body weight gain (BWG) and hematological variables were
      determined for chickens infected with Eimeria tenella (female = 60, male = 63)
      and uninfected (female = 51, male = 45). The hematological variables analyzed
      include the following: packed cell volume (PCV, %), white blood cells (WBC, *
      106/MUl), and red blood cells (RBC, * 106/MUl), as well as differential leucocyte
      percentages of neutrophils, lymphocytes, monocytes, and eosinophils. Body weight
      gain was determined at days 3, 6, 9, 12, and 15. Of the 12 variables analyzed,
      BWG at day 3, monocyte, PCV, and WBC in males and BWG at days 6, 9, and 12, PCV,
      and WBC in female chickens showed significant (P <= 0.01) difference between the
      infected and uninfected. Stepwise discriminant analysis evolved a model that
      could distinguish uninfected from Eimeria-infected chickens. Packed cell volume,
      WBC, BWG at day 3, and lymphocytes emerged the most discriminant between
      uninfected and Eimeria-infected chickens in male chickens. In female chickens,
      PCV, RBC, and BWG at day 3 were identified as most discriminant variables in
      separating the uninfected from Eimeria-infected chickens. Therefore, this study
      suggests that routine blood test and estimates of body weight gain could serve as
      a useful tool for identifying chickens that may be at risk of coccidiosis,
      enabling improvement of preventive measures.

PMID- 29464540
TI  - Genetic analysis of persistency in HF crossbred cattle at an organized farm of
      northern India.
AB  - The present study was undertaken to estimate effect of various genetic and non
      genetic factors on persistency of milk production and to identify the most
      appropriate persistency method that fits best in our environment. In the present
      study, effects of different non-genetic factors, viz. year, season, days to
      attain peak yield, and genetic group based on the level of exotic inheritance on
      persistency of milk yield in crossbred cattle were studied. Data comprised of 686
      first lactation daily milk yield records of crossbred cattle that were maintained
      at GADVASU dairy farm over a period of 25 years from 1991 to 2015 were utilized
      to calculate persistency coefficients by four methods, viz., Ludwick and Peterson
      method (P1), Mahadevan method (P2), ratio method (P3), and Prasad et al. method
      (P4). Overall least squares means for persistency by Ludwick and Peterson method
      (P1), Mahadevan method (P2), ratio method (P3), and Prasad et al. method (P4)
      were 0.896 +/- 0.096, 1.385 +/- 0.224, 187.207 +/- 26.398, and 0.621 +/- 0.098,
      respectively. Effect of sires was significant (P < 0.05) on P2 and P4 methods.
      Effect of genetic group on all four methods was non-significant. Period of
      calving had significant (P < 0.01) effect on persistency of milk yield (P2, P3,
      and P4 methods). Effect of season of calving on persistency of milk yield was
      found to be significant in all estimates obtained by the four methods. Summer and
      autumn calvers were most persistent whereas spring and winter calvers were least
      persistent for (P2, P3, and P4 methods). Persistency of milk yield was
      significantly (P < 0.05) affected by days to attain peak yield in P1 and P2
      methods. Maximum persistency was obtained in animals attaining peak at 41-57 days
      of lactation and minimum in < 41 days for Mahadevan method and ratio method. The
      highest heritability of persistency and minimum value of standard error was
      estimated as 0.275 +/- 0.11 for the Mahadevan method followed by the Prasad
      method (0.197 +/- 0.10) by half sib correlation method. The maximum coefficient
      of variation which indicates available variability was estimated as 20.788% for
      persistency by the Mahadevan method followed by 18.969% for the Prasad method.
      The highest correlation was also observed between P1 and P3 methods by Spearman's
      and Pearson's correlation for least squares breeding value of the sires. On the
      basis of heritability, standard error of heritability, and coefficient of
      variation, it can be concluded that the Mahadevan method followed by the Prasad
      method suits best to our environment for animals in first lactation as well as
      they can be utilized for effective selection for higher persistency in crossbred
      animals of Punjab.

PMID- 29464541
TI  - Sero-prevalence of chlamydiosis in cattle and selected wildlife species at a
      wildlife/livestock interface area of Zimbabwe.
AB  - A study was conducted to investigate the seroprevalence and associated risk
      factors of Chlamydia abortus infection in cattle and some selected wildlife
      species at selected interface areas at the periphery of the Great Limpopo
      Transfrontier Conservation Area in Zimbabwe. Three study sites were selected
      based on the type of livestock-wildlife interface, porous livestock-wildlife
      interface (unrestricted), non-porous livestock-wildlife interface (restricted by
      fencing), and livestock-wildlife non-interface (totally absent or control). Sera
      were collected from cattle aged >= 2 years representing both female and intact
      male. Sera were also collected from selected wild ungulates from Mabalauta
      (porous interface) and Chipinda Pools (non-interface) areas of the Gonarezhou
      National Park. Sera were tested for antibodies to Chlamydia abortus using a CFT.
      A X 2 test was used to assess differences between categories and p < 0.05 was
      considered as significant. In cattle, the overall seroprevalence was 32.7%
      (327/1011; 95% CI 29.5-35.3). A significantly lower seroprevalence was recorded
      for the porous interface (24.2%) compared to the non-porous (42.5%) (p < 0.0001)
      and the non-interface (36.2%) (p = 0.001). Overall, the wet season recorded a
      significantly (p = 0.015) higher seroprevalence than the dry season. In wildlife,
      antibodies were detected in buffaloes (47.7%) and impalas (43.8%) but not in
      kudus. Buffaloes from Chipinda Pools (53.4%) had a significantly (p = 0.036)
      higher seroprevalence than those from Mabalauta (26.1%). The results established
      the presence of chlamydiosis in cattle and selected wildlife and that independent
      infections may be maintained in buffalo populations. Further studies are required
      to clarify chlamydiae circulating between cattle and wildlife.

PMID- 29464542
TI  - Streptomyces tunisialbus sp. nov., a novel Streptomyces species with
      antimicrobial activity.
AB  - A novel actinomycete strain designated S2T was isolated from Tunisian rhizosphere
      soil of Lavandula officinalis. This isolate exhibited broad spectrum
      antibacterial activity against several Gram-positive and Gram-negative bacteria
      and also antifungal activity against yeast and filamentous fungi. The isolate S2T
      presents morphological and chemotaxonomic characteristics typical of the members
      of the genus Streptomyces. Whole cell hydrolysates of S2T were found to contain
      LL-diaminopimelic acid. The major fatty acids were identified as C16:0, anteiso
      C15:0 and iso-C16:0 whereas the predominant menaquinones were found to be MK
      9(H6) and MK-9(H8). The polar lipids were identified as diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol,
      phosphatidylinositol mannoside and three unidentified compounds. The G+C content
      of the genomic DNA was determined to be 71.8 mol%. Phylogenetic analysis based on
      16S rRNA gene sequences indicated that strain S2T belongs to the genus
      Streptomyces and is closely related to Streptomyces netropsis DSM 40259T with
      99.86% sequence similarity. Multi-locus sequence analysis (MLSA) based on four
      house-keeping gene alleles (gyrB, recA, trpB, rpoB) showed that isolate S2T is
      closely related to S. netropsis, with an MLSA distance greater than 0.007. The
      DNA-DNA relatedness between strain S2T and its near phylogenetic neighbour was
      63.6 +/- 2.3%, which is lower than the 70% threshold value for delineation of
      genomic prokaryotic species. This isolate was also distinguished from the type
      strain S. netropsis DSM 40259T, using a combination of morphological and
      physiological features. Based on its phenotypic and molecular properties, strain
      S2T is considered to represent a novel species of the genus Streptomyces, for
      which the name Streptomyces tunisialbus sp. nov. is proposed. The type strain is
      S2T (= JCM 32165T = DSM 105760T).

PMID- 29464543
TI  - Detection of Amyloid Beta (Abeta) Oligomeric Composition Using Matrix-Assisted
      Laser Desorption Ionization Mass Spectrometry (MALDI MS).
AB  - The use of MALDI MS as a fast and direct method to detect the Abeta oligomers of
      different masses is examined in this paper. Experimental results suggest that
      Abeta oligomers are ionized and detected as singly charged ions, and thus, the
      resulting mass spectrum directly reports the oligomer size distribution.
      Validation experiments were performed to verify the MS data against artifacts.
      Mass spectra collected from modified Abeta peptides with different propensities
      for aggregation were compared. Generally, the relative intensities of multimers
      were higher from samples where oligomerization was expected to be more favorable,
      and vice versa. MALDI MS was also able to detect the differences in oligomeric
      composition before and after the incubation/oligomerization step. Such
      differences in sample composition were also independently confirmed with an in
      vitro Abeta toxicity study on primary rat cortical neurons. An additional
      validation was accomplished through removal of oligomers from the sample using
      molecular weight cutoff filters; the resulting MS data correctly reflected the
      removal at the expected cutoff points. The results collectively validated the
      ability of MALDI MS to assess the monomeric/multimeric composition of Abeta
      samples. Graphical Abstract ?.

PMID- 29464544
TI  - Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type
      Lipopolysaccharide Vaccine Candidate.
AB  - Recent advances in lipopolysaccharide (LPS) biology have led to its use in drug
      discovery pipelines, including vaccine and vaccine adjuvant discovery. Desirable
      characteristics for LPS vaccine candidates include both the ability to produce a
      specific antibody titer in patients and a minimal host inflammatory response
      directed by the innate immune system. However, in-depth chemical characterization
      of most LPS extracts has not been performed; hence, biological activities of
      these extracts are unpredictable. Additionally, the most widely adopted workflow
      for LPS structure elucidation includes nonspecific chemical decomposition steps
      before analyses, making structures inferred and not necessarily biologically
      relevant. In this work, several different mass spectrometry workflows that have
      not been previously explored were employed to show proof-of-principle for top
      down LPS primary structure elucidation, specifically for a rough-type mutant (J5)
      E. coli-derived LPS component of a vaccine candidate. First, ion mobility
      filtered precursor ions were subjected to collision induced dissociation (CID) to
      define differences in native J5 LPS v. chemically detoxified J5 LPS (dLPS). Next,
      ultra-high mass resolving power, accurate mass spectrometry was employed for
      unequivocal precursor and product ion empirical formulae generation. Finally, MS3
      analyses in an ion trap instrument showed that previous knowledge about
      dissociation of LPS components can be used to reconstruct and sequence LPS in a
      top down fashion. A structural rationale is also explained for differential
      inflammatory dose-response curves, in vitro, when HEK-Blue hTLR4 cells were
      administered increasing concentrations of native J5 LPS v. dLPS, which will be
      useful in future drug discovery efforts. Graphical Abstract ?.

PMID- 29464545
TI  - Extra-mucosal enucleation is still a safe and feasible treatment option of giant
      esophageal leiomyomas.
AB  - Esophageal leiomyoma (EL) is rare but still the most common benign tumor of the
      esophagus. Extra-mucosal enucleation (EME) is the treatment of choice. Many
      recent reports have favored esophageal resection for giant Esophageal leiomyomas
      (ELs). The consequence of esophageal resection is well known and it would be
      radical to consider it as a preferred treatment for giant EL since most of them
      are still benign. We share case series of five giant ELs managed by EME, avoiding
      a mucosal breach and hence avoiding potentially morbid esophageal resections.

PMID- 29464546
TI  - Gene-diet-related factors of hyperglycaemia in postmenopausal women.
AB  - As ageing and increased body fat are the signs of insulin resistance, we have
      studied whether the presence of Pro12Ala and C1431T of peroxisome proliferator
      activated receptor gamma 2 gene and Trp64Arg of beta 3-adrenergic receptor gene
      may predispose to the hyperglycaemia development in postmenopausal women, who
      have never undergone hypoglycaemic treatment. The distributions of selected
      allele and genotype frequencies were determined by the PCR-RFLP method in normo-
      and hyperglycaemic, who have never been diagnosed and treated for diabetes
      mellitus were measured. The amount of body fat and lean body mass (LBM) were
      assessed by the bioimpedance method and nutritional habits by 7-day dietary
      recall. There were no differences between the distribution of genotypes and the
      allele frequencies of the Pro12Ala, C1431T and Trp64Arg polymorphisms in normo-
      and hyperglycaemic women. Hyperglycaemic women were characterized by visceral
      obesity, hypertension, higher serum insulin and triglycerides, higher intake of
      fat and lower consumption of complex carbohydrates and B vitamins. Normoglycaemic
      women with Pro12Pro polymorphism acquired higher energy from dietary fat (p <
      0.0276) and lower energy from carbohydrates (p < 0.0480) than normoglycaemic
      Ala12 carriers. Subjects with Pro12Pro polymorphism and LBM > 58% of total body
      mass or with Trp64Trp and normal triglycerides have higher chance of
      normoglycaemia. Genotyping for Pro12Ala and Trp64Arg polymorphism in
      postmenopausal women may have the clinical benefit of predicting hyperglycaemia,
      thereby contributing to the prevention of diabetes mellitus development in the
      future. However, not only the genetic background but also the dietary habits
      (intake of fat, carbohydrates and B vitamins) determine the risk of
      hyperglycaemia.

PMID- 29464547
TI  - Comparative evaluation of technetium-99m-diethylenetriaminepentaacetic acid renal
      dynamic imaging versus the Modification of Diet in Renal Disease equation and the
      Chronic Kidney Disease Epidemiology Collaboration equation for the estimation of
      GFR.
AB  - PURPOSE: We compared the performance of technetium-99m
      diethylenetriaminepentaacetic acid (99mTc-DTPA) renal dynamic imaging (RDI), the
      MDRD equation, and the CKD EPI equation to estimate glomerular filtration rate
      (GFR). METHODS: A total of 551 subjects, including CKD patients and healthy
      individuals, were enrolled in this study. Dual plasma sample clearance method of
      99mTc-DTPA was used as the true value for GFR (tGFR). RDI and the MDRD and CKD
      EPI equations for estimating GFR were compared and evaluated. RESULTS: Data
      indicate that RDI and the MDRD equation underestimated GFR and CKD EPI
      overestimated GFR. RDI was associated with significantly higher bias than the
      MDRD and CKD EPI equations. The regression coefficient, diagnostic precision, and
      consistency of RDI were significantly lower than either equation. RDI and the
      MDRD equation underestimated GFR to a greater degree in subjects with tGFR >= 90
      ml/min/1.73 m2 compared with the results obtained from all subjects. In the
      tGFR60-89 ml/min/1.73 m2 group, the precision of RDI was significantly lower than
      that of both equations. In the tGFR30-59 ml/min/1.73 m2 group, RDI had the least
      bias, the most precision, and significantly higher accuracy compared with either
      equation. In tGFR < 30 ml/min/1.73 m2, the three methods had similar performance
      and were not significantly different. CONCLUSIONS: RDI significantly
      underestimates GFR and performs no better than MDRD and CKD EPI equations for GFR
      estimation; thus, it should not be recommended as a reference standard against
      which other GFR measurement methods are assessed. However, RDI better estimates
      GFR than either equation for individuals in the tGFR30-59 ml/min/1.73 m2 group
      and thus may be helpful to distinguish stage 3a and 3b CKD.

PMID- 29464548
TI  - Leptin Involvement in Primary Brain and Pituitary Tumors: Therapeutic Potential,
      Prognostic Value, and Proposed Diagnostic Application.
AB  - Brain tumors are associated with increased mortality and morbidity and are the
      most common cancer type in children and young adults. The present review focuses
      on the interplay between leptin, the most extensively studied adipokine, and the
      onset, development, and treatment of primary brain and intracranial tumors. The
      two main mechanisms for increased leptin levels in intracranial tumor survivors,
      leptin resistance caused by hypothalamic damage, or secondary to obesity, are
      discussed. The contradicting mechanistic observations on leptin being able to
      both promote tumorinogenesis (e.g., in gliomas) as well as inhibit it (e.g., in
      adenomas) are also reported. Additionally, the relevant current and future
      clinical applications, including most notably the proposed use of serum leptin
      measurements for non-invasive brain tumor diagnostics, are also reported.

PMID- 29464549
TI  - Exploring Preconception Care: Insurance Status, Race/Ethnicity, and Health in the
      Pre-pregnancy Period.
AB  - Objective To measure the association of preconception health insurance status
      with preconception health among women in New York City, and examine whether this
      association is modified by race/ethnicity. Methods Using data from the New York
      City Pregnancy Risk Assessment Monitoring System 2009-2011 (n = 3929), we created
      a "Preconception Health Score" (PHS) capturing modifiable behaviors, healthcare
      services utilization, pregnancy intention, and timely entry into prenatal care.
      We then built multivariable logistic regression models to measure the association
      of PHS with health insurance status and race/ethnicity. Results We found PHS to
      be higher among women with private insurance (7.3 +/- 0.07) or public insurance
      (6.3 +/- 0.08) before pregnancy than no insurance (5.9 +/- 0.09) (p < .001).
      However, when stratified by race/ethnicity, the positive association of PHS with
      insurance was absent in the non-white population. Conclusions for Practice Having
      health insurance during the pre-pregnancy period is associated with greater
      health among white women, but not among black or Hispanic women in NYC.

PMID- 29464551
TI  - Immunohistochemical Assessment of the Expression of Biliary Transportation
      Proteins MRP2 and MRP3 in Hepatocellular Carcinoma and in Cholangiocarcinoma.
AB  - Multidrug resistance-associated protein 2 (MRP2) is a multi-specific organic
      anion transporter predominantly expressed in the canalicular membrane of
      hepatocytes, epithelial cells from gallbladder and apical membranes of proximal
      tubular kidney epithelium whereas multidrug resistance-associated protein 3
      (MRP3) is present in the basolateral membrane of hepatocytes and cholangiocytes.
      This study aims to detect the expression of these transporters in hepatocellular
      carcinoma (HCC) and in cholangiocarcinoma (CC), searching for evidences for
      future studies on differential diagnosis and on clinical essays. The
      immunohistochemical reactivity (IHC) of these transporters was assessed in tissue
      microarrays of 80 HCC and 56 CC cases using monoclonal antibodies and compared
      with anatomopathological (AP) variables. The positivity of MRP2 was observed in
      92.3% of HCC and in 96.3% of CC. The detection of high MRP2 expression in HCC was
      not significantly different (p > 0.05) according to the size, number of nodules
      architectural pattern and growth pattern of HCC and CC. Regarding histological
      grades, 22/22 well moderately differentiated HCC versus 50/56 poorly
      differentiated HCC were positive for MRP2. A trend for lower expression in poor
      differentiation HCC was found. And 50/50 well/moderately differentiated CC versus
      2/4 poorly/undifferentiated CC were positive for MRP2. This result showed a
      reduced expression (p = 0,0004) in poorly differentiated CC. MRP3 positivity was
      observed in 18.8% of HCC and was not significantly different according to AP
      parameters. MRP3 was expressed in 44.5% CC, with a trend for lower expression in
      less differentiated CC and significantly lower rates in the ductular histological
      subtype (p = 0.023). The high expression of MRP2 in HCC and in CC is conserved
      regardless most of the anatomopathological parameters, except for a trend of
      lower expression in less differentiated HCC and CC. The observation of lower MRP3
      expression in less differentiated CC and, especially, in the histological subtype
      with expression of hepatic progenitor cell phenotypes leads to future
      opportunities to evaluate the expression of this marker in cholangiocarcinomas.

PMID- 29464550
TI  - Clinical Pharmacokinetics and Pharmacodynamics of Drugs in the Central Nervous
      System.
AB  - Despite contributing significantly to the burden of global disease, the
      translation of new treatment strategies for diseases of the central nervous
      system (CNS) from animals to humans remains challenging, with a high attrition
      rate in the development of CNS drugs. The failure of clinical trials for CNS
      therapies can be partially explained by factors related to
      pharmacokinetics/pharmacodynamics (PK/PD), such as lack of efficacy or improper
      selection of the initial dosage. A focused assessment is needed for CNS-acting
      drugs in first-in-human studies to identify the differences in PK/PD from animal
      models, as well as to choose the appropriate dose. In this review, we summarize
      the available literature from human studies on the PK and PD in brain tissue,
      cerebrospinal fluid, and interstitial fluid for drugs used in the treatment of
      psychosis, Alzheimer's disease and neuro-HIV, and address critical questions in
      the field. We also explore newer methods to characterize PK/PD relationships that
      may lead to more efficient dose selection in CNS drug development.

PMID- 29464552
TI  - Neural response to prosocial scenes relates to subsequent giving behavior in
      adolescents: A pilot study.
AB  - Adolescence is characterized by extensive neural development and sensitivity to
      social context, both of which contribute to engaging in prosocial behaviors.
      Although it is established that prosocial behaviors are linked to positive
      outcomes in adulthood, little is known about the neural correlates of
      adolescents' prosociality. Identifying whether the brain is differentially
      responsive to varying types of social input may be important for fostering
      prosocial behavior. We report pilot results using new stimuli and an ecologically
      valid donation paradigm indicating (1) brain regions typically recruited during
      socioemotional processing evinced differential activation when adolescents
      evaluated prosocial compared with social or noninteractive scenes (N = 20, ages
      13-17 years, MAge = 15.30 years), and (2) individual differences in
      temporoparietal junction recruitment when viewing others' prosocial behaviors
      were related to adolescents' own charitable giving. These novel findings have
      significant implications for understanding how the adolescent brain processes
      prosocial acts and for informing ways to support adolescents to engage in
      prosocial behaviors in their daily lives.

PMID- 29464553
TI  - Heart work after errors: Behavioral adjustment following error commission
      involves cardiac effort.
AB  - Posterror slowing (PES) is the observation that people respond slower on trials
      subsequent to error commissions than on trials subsequent to correct responses.
      Different accounts have been proposed to explain PES. On the one hand, it has
      been suggested that PES arises from an adaptive increase in cognitive control
      following error commission, thereby making people more cautious after making an
      error. On the other hand, PES has been attributed to an orienting response,
      indicating that attention is shifted toward the error. In the present study we
      tested these accounts by investigating the effects of error commission in both
      flanker and switch tasks on two task-evoked cardiac measures: the interbeat
      interval-that is, the interval between two consecutive R peaks-and the RZ
      interval-that is, the interval between the R peak and the Z point-as measured
      using electro- and impedance cardiography, respectively. These measures allowed
      us to measure cardiac deceleration (autonomic orienting) and cardiac effort
      mobilization, respectively. Our results revealed a shorter RZ interval during
      posterror trials, indicating increased effort mobilization following errors. In
      addition, we replicated earlier studies that have shown cardiac slowing during
      error trials. However, multilevel analyses showed that only the posterror
      decrease in RZ interval predicted posterror reaction times, whereas there was no
      positive relationship between error-related cardiac deceleration and posterror
      reaction times. Our results suggest that PES is related to increased cardiac
      effort, supporting a cognitive-control account of PES.

PMID- 29464554
TI  - The influence of self-construals on the ERP response to the rewards for self and
      mother.
AB  - Individual self-construal (independent vs. interdependent) could be temporarily
      modulated by the priming effect. Our previous studies have found that when
      Chinese participants gambled for mother and for self, outcome feedback evoked
      comparable neural responses between two conditions. However, it remains unclear
      if the response to rewards for mother and for self would differ after
      independence self-construal priming. In this study, we manipulated participants'
      self-construal (independent vs. interdependent) before a simple gambling task.
      The event-related potential (ERP) results reveal that when an interdependent self
      construal was primed, the participants exhibited a comparable feedback-related
      negativity (FRN) elicited by outcome feedback for self and for mother. In
      contrast, independent self-construal priming resulted in a greater FRN elicited
      by outcome feedback for self than for mother. Meanwhile, the P3 component was
      insensitive to self-construal manipulation. These findings indicate the
      modulation effect of self-construal priming on the response to rewards for
      others.

PMID- 29464555
TI  - Bacterial Adhesion Pili.
AB  - Escherichia coli bacterial cells produce multiple types of adhesion pili that
      mediate cell-cell and cell-host attachments. These pili (also called 'fimbriae')
      are large biopolymers that are comprised of subunits assembled via a
      sophisticated micro-machinery into helix-like structures that are anchored in the
      bacterial outer membrane. They are commonly essential for initiation of disease
      and thus provide a potential target for antibacterial prevention and treatment.
      To develop new therapeutics for disease prevention and treatment we need to
      understand the molecular mechanisms and the direct role of adhesion pili during
      pathogenesis. These helix-like pilus structures possess fascinating and unique
      biomechanical properties that have been thoroughly investigated using high
      resolution imaging techniques, force spectroscopy and fluid flow chambers. In
      this chapter, we first discuss the structure of pili and the micro-machinery
      responsible for the assembly process. Thereafter, we present methods for
      measurement of the biomechanics of adhesion pili, including optical tweezers.
      Data demonstrate unique biomechanical properties of pili that allow bacteria to
      sustain binding during in vivo fluid shear forces. We thereafter summarize the
      current biomechanical findings related to adhesion pili and show that pili
      biomechanical properties are niche-specific. That is, the data suggest that there
      is an organ-specific adaptation of pili that facilitates infection of the
      bacteria's target tissue. Thus, pilus biophysical properties are an important
      part of Escherichia coli pathogenesis, allowing bacteria to overcome hydrodynamic
      challenges in diverse environments.

PMID- 29464556
TI  - Microbial Rhodopsins.
AB  - Microbial rhodopsins (MRs) are a large family of photoactive membrane proteins,
      found in microorganisms belonging to all kingdoms of life, with new members being
      constantly discovered. Among the MRs are light-driven proton, cation and anion
      pumps, light-gated cation and anion channels, and various photoreceptors. Due to
      their abundance and amenability to studies, MRs served as model systems for a
      great variety of biophysical techniques, and recently found a great application
      as optogenetic tools. While the basic aspects of microbial rhodopsins functioning
      have been known for some time, there is still a plenty of unanswered questions.
      This chapter presents and summarizes the available knowledge, focusing on the
      functional and structural studies.

PMID- 29464557
TI  - The Structural Basis for the Extraordinary Energy-Transfer Capabilities of the
      Phycobilisome.
AB  - Light absorption is the initial step in the photosynthetic process. In all
      species, most of the light is absorbed by dedicated pigment-protein complexes
      called light harvesting complexes or antenna complexes. In the case of
      cyanobacteria and red-algae, photosynthetic organisms found in a wide variety of
      ecological niches, the major antenna is called the Phycobilisome (PBS). The PBS
      has many unique characteristics that sets it apart from the antenna complexes of
      other organisms (bacteria, algae and plants). These differences include the type
      of light absorbing chromophores, the protein environment of the chromophores, the
      method of assembly and association and the intercellular location with respect to
      the photosynthetic reaction centers (RCs). Since the final goal of all antenna
      complexes is the same - controlled absorption and transfer of the energy of the
      sun to the RCs, the unique structural and chemical differences of the PBS also
      require unique energy transfer mechanisms and pathways. In this review we will
      describe in detail the structural facets that lead to a mature PBS, followed by
      an attempt to understand the energy transfer properties of the PBS as they have
      been measured experimentally.

PMID- 29464558
TI  - Bacterial Mechanosensitive Channels.
AB  - Mechanosensitive (MS) channels protect bacteria against hypo-osmotic shock and
      fulfil additional functions. Hypo-osmotic shock leads to high turgor pressure
      that can cause cell rupture and death. MS channels open under these conditions
      and release unspecifically solutes and consequently the turgor pressure. They can
      recognise the raised pressure via the increased tension in the cell membrane.
      Currently, a better understanding how MS channels can sense tension on molecular
      level is developing because the interaction of the lipid bilayer with the channel
      is being investigated in detail. The MS channel of large conductance (MscL) and
      of small conductance (MscS) have been distinguished and studied in molecular
      detail. In addition, larger channels were found that contain a homologous region
      corresponding to MscS so that MscS represents a family of channels. Often several
      members of this family are present in a species. The importance of this family is
      underlined by the fact that members can be found not only in bacteria but also in
      higher organisms. While MscL and MscS have been studied for years in particular
      by electrophysiology, mutagenesis, molecular dynamics, X-ray crystallography and
      other biophysical techniques, only recently more details are emerging about other
      members of the MscS-family.

PMID- 29464559
TI  - Monoamine Oxidases.
AB  - Monoamine oxidases A and B (MAO A and B) are mammalian flavoenzymes bound to the
      outer mitochondrial membrane. They were discovered almost a century ago and they
      have been the subject of many biochemical, structural and pharmacological
      investigations due to their central role in neurotransmitter metabolism.
      Currently, the treatment of Parkinson's disease involves the use of selective MAO
      B inhibitors such as rasagiline and safinamide. MAO inhibition was shown to exert
      a general neuroprotective effect as a result of the reduction of oxidative stress
      produced by these enzymes, which seems to be relevant also in non-neuronal
      contexts. MAOs were successfully expressed as recombinant proteins in Pichia
      pastoris, which allowed a thorough biochemical and structural characterization.
      These enzymes are characterized by a globular water-soluble main body that is
      anchored to the mitochondrial membrane through a C-terminal alpha-helix, similar
      to other bitopic membrane proteins. In both MAO A and MAO B the enzyme active
      site consists of a hydrophobic cavity lined by residues that are conserved in the
      two isozymes, except for few details that determine substrate and inhibitor
      specificity. In particular, human MAO B features a dual-cavity active site whose
      conformation depends on the size of the bound ligand. This article provides a
      comprehensive and historical review of MAOs and the state-of-the-art of these
      enzymes as membrane drug targets.

PMID- 29464561
TI  - Mitochondrial Respiratory Chain Complexes.
AB  - Mitochondria are the power stations of the eukaryotic cell, using the energy
      released by the oxidation of glucose and other sugars to produce ATP. Electrons
      are transferred from NADH, produced in the citric acid cycle in the mitochondrial
      matrix, to oxygen by a series of large protein complexes in the inner
      mitochondrial membrane, which create a transmembrane electrochemical gradient by
      pumping protons across the membrane. The flow of protons back into the matrix via
      a proton channel in the ATP synthase leads to conformational changes in the
      nucleotide binding pockets and the formation of ATP. The three proton pumping
      complexes of the electron transfer chain are NADH-ubiquinone oxidoreductase or
      complex I, ubiquinone-cytochrome c oxidoreductase or complex III, and cytochrome
      c oxidase or complex IV. Succinate dehydrogenase or complex II does not pump
      protons, but contributes reduced ubiquinone. The structures of complex II, III
      and IV were determined by x-ray crystallography several decades ago, but complex
      I and ATP synthase have only recently started to reveal their secrets by advances
      in x-ray crystallography and cryo-electron microscopy. The complexes I, III and
      IV occur to a certain extent as supercomplexes in the membrane, the so-called
      respirasomes. Several hypotheses exist about their function. Recent cryo-electron
      microscopy structures show the architecture of the respirasome with near-atomic
      detail. ATP synthase occurs as dimers in the inner mitochondrial membrane, which
      by their curvature are responsible for the folding of the membrane into cristae
      and thus for the huge increase in available surface that makes mitochondria the
      efficient energy plants of the eukaryotic cell.

PMID- 29464560
TI  - Transient Receptor Potential (TRP) Channels.
AB  - Transient Receptor Potential (TRP) channels are evolutionarily conserved integral
      membrane proteins. The mammalian TRP superfamily of ion channels consists of 28
      cation permeable channels that are grouped into six subfamilies based on sequence
      homology (Fig. 6.1). The canonical TRP (TRPC) subfamily is known for containing
      the founding member of mammalian TRP channels. The vanilloid TRP (TRPV) subfamily
      has been extensively studied due to the heat sensitivity of its founding member.
      The melastatin-related TRP (TRPM) subfamily includes some of the few known bi
      functional ion channels, which contain functional enzymatic domains. The ankyrin
      TRP (TRPA) subfamily consists of a single chemo-nociceptor that has been proposed
      to be a target for analgesics. The mucolipin TRP (TRPML) subfamily channels are
      found primarily in intracellular compartments and were discovered based on their
      critical role in type IV mucolipidosis (ML-IV). The polycystic TRP (TRPP)
      subfamily is a diverse group of proteins implicated in autosomal dominant
      polycystic kidney disease (ADPKD). Overall, this superfamily of channels is
      involved in a vast array of physiological and pathophysiological processes making
      the study of these channels imperative to our understanding of subcellular
      biochemistry.

PMID- 29464562
TI  - The SarcoEndoplasmic Reticulum Calcium ATPase.
AB  - The calcium pump (a.k.a. Ca2+-ATPase or SERCA) is a membrane transport protein
      ubiquitously found in the endoplasmic reticulum (ER) of all eukaryotic cells. As
      a calcium transporter, SERCA maintains the low cytosolic calcium level that
      enables a vast array of signaling pathways and physiological processes (e.g.
      synaptic transmission, muscle contraction, fertilization). In muscle cells, SERCA
      promotes relaxation by pumping calcium ions from the cytosol into the lumen of
      the sarcoplasmic reticulum (SR), the main storage compartment for intracellular
      calcium. X-ray crystallographic studies have provided an extensive understanding
      of the intermediate states that SERCA populates as it progresses through the
      calcium transport cycle. Historically, SERCA is also known to be regulated by
      small transmembrane peptides, phospholamban (PLN) and sarcolipin (SLN). PLN is
      expressed in cardiac muscle, whereas SLN predominates in skeletal and atrial
      muscle. These two regulatory subunits play critical roles in cardiac
      contractility. While our understanding of these regulatory mechanisms are still
      developing, SERCA and PLN are one of the best understood examples of peptide
      transporter regulatory interactions. Nonetheless, SERCA appeared to have only two
      regulatory subunits, while the related sodium pump (a.k.a. Na+, K+-ATPase) has at
      least nine small transmembrane peptides that provide tissue specific regulation.
      The last few years have seen a renaissance in our understanding of SERCA
      regulatory subunits. First, structures of the SERCA-SLN and SERCA-PLN complexes
      revealed molecular details of their interactions. Second, an array of
      micropeptides concealed within long non-coding RNAs have been identified as new
      SERCA regulators. This chapter will describe our current understanding of SERCA
      structure, function, and regulation.

PMID- 29464563
TI  - Organization of Plant Photosystem II and Photosystem I Supercomplexes.
AB  - In nature, plants are continuously exposed to varying environmental conditions.
      They have developed a wide range of adaptive mechanisms, which ensure their
      survival and maintenance of stable photosynthetic performance. Photosynthesis is
      delicately regulated at the level of the thylakoid membrane of chloroplasts and
      the regulatory mechanisms include a reversible formation of a large variety of
      specific protein-protein complexes, supercomplexes or even larger assemblies
      known as megacomplexes. Revealing their structures is crucial for better
      understanding of their function and relevance in photosynthesis. Here we focus
      our attention on the isolation and a structural characterization of various large
      protein supercomplexes and megacomplexes, which involve Photosystem II and
      Photosystem I, the key constituents of photosynthetic apparatus. The photosystems
      are often attached to other protein complexes in thylakoid membranes such as
      light harvesting complexes, cytochrome b 6 f complex, and NAD(P)H dehydrogenase.
      Structural models of individual supercomplexes and megacomplexes provide
      essential details of their architecture, which allow us to discuss their function
      as well as physiological significance.

PMID- 29464564
TI  - The Cytochrome b 6 f Complex: Biophysical Aspects of Its Functioning in
      Chloroplasts.
AB  - This chapter presents an overview of structural properties of the cytochrome
      (Cyt) b 6 f complex and its functioning in chloroplasts. The Cyt b 6 f complex
      stands at the crossroad of photosynthetic electron transport pathways, providing
      connectivity between Photosystem (PSI) and Photosysten II (PSII) and pumping
      protons across the membrane into the thylakoid lumen. After a brief review of the
      chloroplast electron transport chain, the consideration is focused on the
      structural organization of the Cyt b 6 f complex and its interaction with
      plastoquinol (PQH2, reduced form of plastoquinone), a mediator of electron
      transfer from PSII to the Cyt b 6 f complex. The processes of PQH2 oxidation by
      the Cyt b 6 f complex have been considered within the framework of the Mitchell's
      Q-cycle. The overall rate of the intersystem electron transport is determined by
      PQH2 turnover at the quinone-binding site Qo of the Cyt b 6 f complex. The rate
      of PQH2 oxidation is controlled by the intrathylakoid pHin, which value
      determines the protonation/deprotonation events in the Qo-center. Two other
      regulatory mechanisms associated with the Cyt b 6 f complex are briefly
      overviewed: (i) redistribution of electron fluxes between alternative (linear and
      cyclic) pathways, and (ii) "state transitions" related to redistribution of solar
      energy between PSI and PSII.

PMID- 29464566
TI  - Conformational Equilibrium of Human Platelet Integrin Investigated by Three
      Dimensional Electron Cryo-Microscopy.
AB  - Integrins are bidirectional transmembrane receptors that play central roles in
      hemostasis and arterial thrombosis. They have been subject to structural studies
      for many years, in particular using X-ray crystallography, nuclear magnetic
      resonance spectroscopy, and two-dimensional negative stain electron microscopy.
      Despite considerable progress, a full consensus on the molecular mechanism of
      integrin activation is still lacking. Three-dimensional reconstructions of full
      length human platelet integrin alphaIIbbeta3 in lipid-bilayer nanodiscs obtained
      by electron cryo-microscopy and single-particle reconstruction have shed new
      light on the activation process. These studies show that integrin alphaIIbbeta3
      exists in a continuous conformational equilibrium ranging from a compact nodular
      conformation similar to that obtained in crystal structures to a fully extended
      state with the leg domains separated. This equilibrium is shifted towards the
      extended conformation when extracellular ligands, cytosolic activators and lipid
      bilayer nanodiscs are added. Addition of cytosolic activators and extracellular
      ligands in the absense of nanodiscs produces significantly less dramatic shifts,
      emphasizing the importance of the membrane bilayer in the activation process.

PMID- 29464567
TI  - Mitochondrial Proteolipid Complexes of Creatine Kinase.
AB  - Isoforms of creatine kinase (CK) generate and use phosphocreatine, a concentrated
      and highly diffusible cellular "high energy" intermediate, for the main purpose
      of energy buffering and transfer in order to maintain cellular energy
      homeostasis. The mitochondrial CK isoform (mtCK) localizes to the mitochondrial
      intermembrane and cristae space, where it assembles into peripherally membrane
      bound, large cuboidal homooctamers. These are part of proteolipid complexes
      wherein mtCK directly interacts with cardiolipin and other anionic phospholipids,
      as well as with the VDAC channel in the outer membrane. This leads to a
      stabilization and cross-linking of inner and outer mitochondrial membrane,
      forming so-called contact sites. Also the adenine nucleotide translocator of the
      inner membrane can be recruited into these proteolipid complexes, probably
      mediated by cardiolipin. The complexes have functions mainly in energy transfer
      to the cytosol and stimulation of oxidative phosphorylation, but also in
      restraining formation of reactive oxygen species and apoptosis. In vitro evidence
      indicates a putative role of mtCK in mitochondrial phospholipid distribution, and
      most recently a role in thermogenesis has been proposed. This review summarizes
      the essential structural and functional data of these mtCK complexes and
      describes in more detail the more recent advances in phospholipid interaction,
      thermogenesis, cancer and evolution of mtCK.

PMID- 29464565
TI  - Ryanodine Receptor Structure and Function in Health and Disease.
AB  - Ryanodine receptors (RyRs) are ubiquitous intracellular calcium (Ca2+) release
      channels required for the function of many organs including heart and skeletal
      muscle, synaptic transmission in the brain, pancreatic beta cell function, and
      vascular tone. In disease, defective function of RyRs due either to stress
      (hyperadrenergic and/or oxidative overload) or genetic mutations can render the
      channels leaky to Ca2+ and promote defective disease-causing signals as observed
      in heat failure, muscular dystrophy, diabetes mellitus, and neurodegerative
      disease. RyRs are massive structures comprising the largest known ion channel
      bearing macromolecular complex and exceeding 3 million Daltons in molecular
      weight. RyRs mediate the rapid release of Ca2+ from the endoplasmic/sarcoplasmic
      reticulum (ER/SR) to stimulate cellular functions through Ca2+-dependent
      processes. Recent advances in single-particle cryogenic electron microscopy (cryo
      EM) have enabled the determination of atomic-level structures for RyR for the
      first time. These structures have illuminated the mechanisms by which these
      critical ion channels function and interact with regulatory ligands. In the
      present chapter we discuss the structure, functional elements, gating and
      activation mechanisms of RyRs in normal and disease states.

PMID- 29464568
TI  - The Vacuolar ATPase - A Nano-scale Motor That Drives Cell Biology.
AB  - The vacuolar H+-ATPase (V-ATPase) is a ~1 MDa membrane protein complex that
      couples the hydrolysis of cytosolic ATP to the transmembrane movement of protons.
      In essentially all eukaryotic cells, this acid pumping function plays critical
      roles in the acidification of endosomal/lysosomal compartments and hence in
      transport, recycling and degradative pathways. It is also important in acid
      extrusion across the plasma membrane of some cells, contributing to homeostatic
      control of cytoplasmic pH and maintenance of appropriate extracellular acidity.
      The complex, assembled from up to 30 individual polypeptides, operates as a
      molecular motor with rotary mechanics. Historically, structural inferences about
      the eukaryotic V-ATPase and its subunits have been made by comparison to the
      structures of bacterial homologues. However, more recently, we have developed a
      much better understanding of the complete structure of the eukaryotic complex, in
      particular through advances in cryo-electron microscopy. This chapter explores
      these recent developments, and examines what they now reveal about the catalytic
      mechanism of this essential proton pump and how its activity might be regulated
      in response to cellular signals.

PMID- 29464569
TI  - Correction to: Budget Impact Analysis of Brivaracetam Adjunctive Therapy for
      Partial-Onset Epileptic Seizures in Valencia Community, Spain.
AB  - In the original publication, the abstract, conclusion was incorrectly published.

PMID- 29464570
TI  - Hepatic esterase activity is increased in hepatocyte-like cells derived from
      human embryonic stem cells using a 3D culture system.
AB  - OBJECTIVES: The aim of the study is to generate a spherical three-dimensional
      (3D) aggregate of hepatocyte-like cells (HLCs) differentiated from human
      embryonic stem cells and to investigate the effect of the 3D environment on
      hepatic maturation and drug metabolism. RESULTS: Quantitative real-time PCR
      analysis indicated that gene expression of mature hepatocyte markers, drug
      metabolizing enzymes, and hepatic transporters was significantly higher in HLCs
      cultured in the 3D system than in those cultured in a two-dimensional system (p <
      0.001). Moreover, hepatocyte-specific functions, including albumin secretion and
      bile canaliculi formation, were increased in HLCs cultured in the 3D system. In
      particular, 3D spheroidal culture increased expression of CES1 and BCHE, which
      encode hepatic esterases (p < 0.001). The enhanced activities of these hepatic
      esterases were confirmed by the cholinesterase activity assay and the increased
      susceptibility of HLCs to oseltamivir, which is metabolized by CES1. CONCLUSIONS:
      3D spheroidal culture enhances the maturation and drug metabolism of stem cell
      derived HLCs, and this may help to optimize hepatic differentiation protocols for
      hepatotoxicity testing.

PMID- 29464571
TI  - Direct electrospinning of poly(vinyl butyral) onto human dermal fibroblasts using
      a portable device.
AB  - OBJECTIVE: To demonstrate that uniform poly(vinyl butyral) (PVB) fibres can be
      safely electrospun onto a monolayer of human dermal fibroblasts using a portable
      device. RESULTS: PVB in solvent mixtures containing various amounts of ethanol
      and water was electrospun. Six percent (weight-to-volume ratio) PVB in a 9:1
      ethanol:water ratio was the solution with the highest content in water that could
      be electrospun into consistent fibres with an average diameter of 0.9 MUm (+/-
      0.1 MUm). Four and five percent PVB solutions created beaded fibres. A 8:2
      ethanol:water solution lead to microbead formation while a 7:3 ethanol:water mix
      failed to fully dissolve. The selected solution was successfully electrospun onto
      a monolayer of human dermal fibroblasts and the process had no significant effect
      (p < 0.05) on cell viability compared to the control without fibres. CONCLUSIONS:
      PVB-ethanol-water solutions could be electrospun without damaging the exposed
      cell layer. However, further work is required to demonstrate the long-term effect
      of PVB as a wound healing material.

PMID- 29464572
TI  - Brain Renin-Angiotensin System Blockade Attenuates Methamphetamine-Induced
      Hyperlocomotion and Neurotoxicity.
AB  - Methamphetamine (METH) abuse has become a major public health concern worldwide
      without approved pharmacotherapies. The brain renin-angiotensin system (RAS) is
      involved in the regulation of neuronal function as well as neurological
      disorders. Angiotensin II (Ang II), which interacts with Ang II type 1 receptor
      (AT1-R) in the brain, plays an important role as a neuromodulator in dopaminergic
      transmission. However, the role of brain RAS in METH-induced behavior is largely
      unknown. Here, we revealed that repeated METH administration significantly
      upregulated the expression of AT1-R in the striatum of mice, but downregulated
      dopamine D3 receptor (D3R) expression. A specific AT1-R blocker telmisartan,
      which can penetrate the brain-blood barrier (BBB), or genetic deletion of AT1-R
      was sufficient to attenuate METH-triggered hyperlocomotion in mice. However,
      intraperitoneal injection of AT1-R blocker losartan, which cannot penetrate BBB,
      failed to attenuate METH-induced behavior. Moreover, intra-striatum re-expression
      of AT1 with lentiviral virus expressing AT1 reversed the weakened locomotor
      activity of AT1-/- mice treated with METH. Losartan alleviated METH-induced
      cytotoxicity in SH-SY5Y cells in vitro, which was accompanied by upregulated
      expressions of D3R and dopamine transporter. In addition, intraperitoneal
      injection of perindopril, which is a specific ACE inhibitor and can penetrate
      BBB, significantly attenuated METH-induced hyperlocomotor activity. Collectively,
      our results show that blockade of brain RAS attenuates METH-induced
      hyperlocomotion and neurotoxicity possibly through modulation of D3R expression.
      Our findings reveal a novel role of Ang II-AT1-R in METH-induced hyperlocomotion.

PMID- 29464574
TI  - Targeted Pituitary Adenylate Cyclase-Activating Peptide Therapies for Migraine.
AB  - Here, we review the role of pituitary adenylate cyclase-activating peptide-38
      (PACAP38) in migraine pathophysiology and data implicating PAC1 receptor as a
      future drug target in migraine. Much remains to be fully elucidated about
      migraine pathophysiology, but recent attention has focused on signaling molecule
      PACAP38, a vasodilator able to induce migraine attacks in patients who experience
      migraine without aura. PACAP38, with marked and sustained effect, dilates
      extracerebral arteries but not the middle cerebral artery. The selective affinity
      of PACAP38 to the PAC1 receptor makes this receptor a highly interesting and
      potential novel target for migraine treatment. Efficacy of antagonism of this
      receptor should be investigated in randomized clinical trials.

PMID- 29464573
TI  - Intrinsic Inflammation Is a Potential Anti-Epileptogenic Target in the
      Organotypic Hippocampal Slice Model.
AB  - Understanding the mechanisms of epileptogenesis is essential to develop novel
      drugs that could prevent or modify the disease. Neuroinflammation has been
      proposed as a promising target for therapeutic interventions to inhibit the
      epileptogenic process that evolves from traumatic brain injury. However, it
      remains unclear whether cytokine-related pathways, particularly TNFalpha
      signaling, have a critical role in the development of epilepsy. In this study, we
      investigated the role of innate inflammation in an in vitro model of post
      traumatic epileptogenesis. We combined organotypic hippocampal slice cultures,
      representing an in vitro model of post-traumatic epilepsy, with multi-electrode
      array recordings to directly monitor the development of epileptiform activity and
      to examine the concomitant changes in cytokine release, cell death, and glial
      cell activation. We report that synchronized ictal- and interictal-like
      activities spontaneously evolve in this culture. Dynamic changes in the release
      of the pro-inflammatory cytokines IL-1beta, TNFalpha, and IL-6 were observed
      throughout the culture period (3 to 21 days in vitro) with persistent activation
      of microglia and astrocytes. We found that neutralizing TNFalpha with a
      polyclonal antibody significantly reduced ictal discharges, and this effect
      lasted for 1 week after antibody washout. Neither phenytoin nor an anti-IL-6
      polyclonal antibody was efficacious in inhibiting the development of epileptiform
      activity. Our data show a sustained effect of the anti-TNFalpha antibody on the
      ictal progression in organotypic hippocampal slice cultures supporting the
      critical role of inflammatory mediators in epilepsy and establishing a proof-of
      principle evidence for the utility of this preparation to test the therapeutic
      effects of anti-inflammatory treatments.

PMID- 29464576
TI  - Abstracts of the European symposium on the prevention of congenital anomalies.

PMID- 29464575
TI  - Rapid method for purification of Clostridium botulinuh type C neurotoxin by High
      Performance Liquid Chromatography (HPLC ).
AB  - The culture supernatant of Clostridium botulinum type C, concentrated by addition
      of RNA, acid precipitation and subsequent protamine treatment was used as
      starting material for rapid purification of L toxin (mol. wt. ca. 500K) and M
      toxin (mol. wt. ca. 350K) of C1 neurotoxin by ion-exchange chromatography on a
      Mono S column by fast performance liquid chromatography (FPLC). L and M toxins
      were highly purified further by gel permeation chromatography through a TSK
      G3000SW column at pH 6.0 by high performance liquid chromatography (HPLC).
      Purified S toxin (mol. wt. ca. 150K, Cl neurotoxin without a nontoxic component)
      was then obtained from L toxin rapidly by gel permeation chromatography at pH 7.3
      through a TSK G3000SW column by HPLC. Purified S toxin was also obtained rapidly
      from M and L toxins by ion-exchange chromatography on a Mono Q column at pH 8.0
      using an FPLC system. The purified preparations of L, M and S toxins gave single
      bands on conventional polyacrylamide gel electrophoresis, and had specific
      activities of 2.8, 6.7, and 14-21 * 107 LD50/mg N, respectively, in mice. On
      immunoelectrophoresis, purified S toxin gave a single arc against anti-crude
      toxin serum. The yield of toxicity as L and M toxins was 73.1% (32.5% as L toxin
      and 40.6% as M toxin) from the protamine-treated concentrated culture
      supernatant. The recovery of toxicity as S toxin from purified L or M toxin was
      almost 100% (97.6-100% of L toxin and 97.5% of M toxin). These procedures provide
      a rapid method for purifying L and M toxins, which have stable toxicities. The
      method will also be very useful for rapid preparation of the toxic component (S
      toxin) of C1 neurotoxin, which is unstable, in small amounts from the L and M
      toxins just before its use in experiments.

PMID- 29464577
TI  - Behavioral consequences of children with sleep-disordered breathing after
      adenotonsillectomy.
AB  - BACKGROUND: Adenotonsillectomy (AT) has been an effective treatment for sleep
      disordered breathing (SDB) in children, and several studies described the risk of
      postoperative weight gain and obesity in children treated with AT. The present
      study aimed to evaluate behavioral improvements in children with SDB one year
      after adenotonsillectomy and to investigate an influence of postoperative weight
      gain on behaviors. METHODS: The study included 170 children aged 5-11 years who
      underwent adenotonsillectomy for SDB and 150 controls. Body mass index percentile
      was obtained for age and gender, and parental sleep-related breathing disorder
      (SRBD) questionnaire was used to assess the severity of SDB. Psychological
      assessment was performed pre- and post-adenotonsillectomy using standardized
      questionnaires including strength and difficulties questionnaire, children's
      depression inventory and screen for child anxiety-related emotional disorder.
      RESULTS: The mean age of 170 patients was 7.7 +/- 1.5 years with 73 (42.9%) girls
      and 97 (57.1%) boys. The mean follow-up period were 15.4 +/- 2.7 months. The
      patients had shown significant improvements in SDB scores as well as in
      questionnaire-based behavioral problems after adenotonsillectomy. The odds of a
      child being overweight were significantly increased after adenotonsillectomy.
      Less improvements in hyperactivity and conduct problems were observed in the
      patients with older ages, higher SRBD scores, and overweight/obesity at 1-year
      follow-up after adenotonsillectomy. CONCLUSION: These data suggest that abnormal
      behavioral outcomes should be evaluated postoperatively, which potentially could
      be reduced with the early adenotonsillectomy and adequate postoperative weight
      control.

PMID- 29464578
TI  - Incidence and risk factors of post-phototherapy neonatal rebound
      hyperbilirubinemia.
AB  - BACKGROUND: To determine the incidence and risk factors of post-phototherapy
      rebound hyperbilirubinemia because data about bilirubin rebound in neonates are
      lacking and few studies have concerned this condition. METHODS: A prospective
      observational study was conducted on 500 neonates with indirect
      hyperbilirubinemia who were treated according to standard guidelines. Total serum
      bilirubin (TSB) was measured at 24-36 h after phototherapy; significant bilirubin
      rebound (SBR) is considered as increasing TSB that needs reinstitution of
      phototherapy. RESULTS: A total of 124 (24.9%) neonates developed SBR with TSB
      increased by 3.4 (2.4-11.2) mg/dL after stopping phototherapy. Multiple logistic
      regression model revealed the following significant risk factors for rebound: low
      birth weight (B = 1.3, P <  0.001, OR 3.5), suspected sepsis (B = 2.5, P < 
      0.001, OR 12.6), exposure to intensive phototherapy (B =  0.83, P =  0.03, OR
      2.3), hemolysis (B =  1.2, P <  0.001, OR 3.1), high discharge bilirubin level (B
      =  0.3, P =  0.001, OR 1.3), and short duration of conventional phototherapy (B =
      - 1.2, P <  0.001, OR 0.3). CONCLUSIONS: SBR should be considered in neonates
      with hemolysis, low birth weight, suspected sepsis, short duration of
      conventional phototherapy, exposure to intensive phototherapy, and relatively
      high discharge TSB. These risk factors should be taken into account when planning
      post-phototherapy follow-up.

PMID- 29464579
TI  - Oxcarbazepine oral suspension in young pediatric patients with partial seizures
      and/or generalized tonic-clonic seizures in routine clinical practice in China: a
      prospective observational study.
AB  - BACKGROUND: This study aimed to assess efficacy and safety of oxcarbazepine (OXC)
      oral suspension in pediatric patients aged 2-5 years with partial seizures (PS)
      and/or generalized tonic-clonic seizures (GTCS) in real-world clinical practice
      in China. METHODS: This 26-week, prospective, single-arm, multicenter,
      observational study recruited pediatric patients aged 2-5 years with PS or GTCS
      suitable for OXC oral suspension treatment based on physicians' judgments from 11
      medical centers in China. Enrolled subjects started OXC oral suspension treatment
      as monotherapy or in combination with other antiepileptic drugs. Primary efficacy
      outcome was the percentage of pediatric subjects achieving >= 50% seizure
      frequency reduction at the end of the 26-week treatment. Secondary efficacy
      related parameters and safety parameters such as adverse events (AEs) and serious
      AEs (SAEs) were also monitored during the 26-week treatment period. RESULTS: Six
      hundred and six pediatric patients were enrolled and 531 (87.6%) completed the
      study. After 26 weeks of treatment, 93.3% subjects achieved >= 50% seizure
      frequency reduction, and 81.8% achieved 100% seizure frequency reduction compared
      to baseline. Among different seizure types, OXC was effective in all subjects
      with simple PS and in > 90% of subject with other type of seizure present in the
      study. AEs were observed in 49 (8.1%) subjects. Only three subjects experienced
      SAE. Rash (n = 18, 2.97%) was the most common AE. Only 17 subjects discontinued
      due to AEs. CONCLUSION: This study, reporting the real-world data, further
      confirms the efficacy and good safety profile of OXC oral suspension in Chinese
      pediatric patients aged 2-5 years with PS and/or GTCS.

PMID- 29464580
TI  - Outcome after early mobilization following hip reconstruction in children with
      developmental hip dysplasia and luxation.
AB  - BACKGROUND: Most orthopedic surgeons prefer spica cast immobilization in children
      for 4 to 12 weeks after surgical hip reconstruction in children with
      developmental hip dysplasia. This challenging treatment may be associated with
      complications. Studies are lacking that focus on early mobilization without
      casting for postoperative care after hip reconstruction. METHODS: Twenty-seven
      children (3.4+/-2.0 years), including 33 hips with developmental hip dysplasia
      (DDH) and dislocation of the hip (Tonnis grade 1 to 4), who underwent hip
      reconstruction (Dega acetabuloplasty, varisation-derotation osteotomy and
      facultative open reduction) were retrospectively included in this study.
      Postoperatively the patients were placed in an individual foam shell with 30
      degrees of hip abduction, hip extension, and neutral rotation. Early mobilization
      physiotherapy was performed within the first few days after the surgery under
      epidural anaesthesia. Full weight bearing was allowed after 3-4 weeks. All
      children received a clinical examination and radiographic evaluation before and
      after surgical intervention. The follow-up period was 12.3+/-2.9 months. RESULTS:
      On average, the postoperative acetabular index decreased significantly from 36.9
      to 21.7 degrees and the center-edge angle increased from 9.9 to 28.6 degrees. All
      hips had reached Tonnis grade 1 at the time of the last follow-up. No
      complications such as dislocation of the bone wedge, avascular necrosis of the
      acetabulum or femur, lack of non-union, or nerve injury, were reported.
      CONCLUSIONS: In this cohort study, hip reconstruction was successful according to
      clinical and radiographic outcome parameters after early mobilization without
      cast therapy. Early mobilization may be used as an alternative treatment option
      after hip reconstruction in DDH.

PMID- 29464581
TI  - Urinary neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C
      measurements for early diagnosis of acute kidney injury in children admitted to
      PICU.
AB  - BACKGROUND: Acute kidney injury (AKI) is common in critically ill children with
      significant mortality and morbidity. Serum creatinine is an insensitive and late
      biomarker compared to newly proposed AKI biomarkers. METHODS: Prospective study
      in pediatric intensive care unit (PICU) over three months to compare between
      serum cystatin-C (s-Cys-C) and urinary neutrophil gelatinase-associated lipocalin
      (uNGAL) as AKI biomarkers at multiple time points with pediatric risk, injury,
      failure, loss, end-stage renal disease (pRIFLE) classification in diagnosing AKI.
      RESULTS: Forty children were recruited. Of these 40 children, 22 developed AKI
      according to pRIFLE criteria. There was no significant difference between AKI and
      non-AKI in age (P = 0.29). Post cardiac surgery, renal insult was the main cause
      of AKI (27.3%). There was a twofold increased risk of incident AKI in those
      patients with high baseline uNGAL at PICU admission and almost a fourfold
      increased risk in patients with high baseline s-Cys-C at PICU admission. uNGAL
      levels were highly predictive of AKI during the follow-up period [area under the
      curve (AUC) = 0.76, 95% confidence interval (CI) 0.61-0.92]. The cutoff point
      with the highest correctly classified proportion was 223 ng/mL (>= 12 centiles)
      which correctly predict 80.0% patients with AKI, with a corresponding sensitivity
      of 72.7% and a specificity of 89.9%. AUC for s-Cys-C was 0.86 (95% CI 0.75-0.97),
      and the highest correctly classified proportion was 1009 ug/L (>= 13 centiles);
      75% of patients with AKI, with a corresponding sensitivity of 63.6% and a
      specificity of 88.9%. CONCLUSION: uNGAL and s-Cys-C predicts AKI early in
      critically ill children.

PMID- 29464582
TI  - Rebamipide in Functional and Organic Dyspepsia: Sometimes the Best Offense Is a
      Good Defense.

PMID- 29464584
TI  - The Prevalence and Risk of Fecal Incontinence in Patients with Cystic Fibrosis:
      Nothing to Sneeze At.

PMID- 29464586
TI  - A Tribute to Paul H. Guth, MD (1927-2017).

PMID- 29464583
TI  - Intestinal Involvement in Systemic Sclerosis: A Clinical Review.
AB  - Systemic sclerosis (SSc) is a chronic systemic disease characterized by
      microvasculopathy, autoantibodies, and extensive fibrosis. Intestinal involvement
      is frequent in SSc and represents a significant cause of morbidity. The
      pathogenesis of intestinal involvement includes vascular damage, nerve
      dysfunction, smooth muscle atrophy, and fibrosis, causing hypomotility, which
      leads to small intestinal bacterial overgrowth (SIBO), malabsorption,
      malnutrition, diarrhea, pseudo-obstruction, constipation, pneumatosis
      intestinalis, and fecal incontinence. Manifestations are often troublesome and
      reduce quality of life and life expectancy. Assessment of intestinal involvement
      includes screening for small intestine hypomotility, malnutrition, SIBO, and
      anorectal dysfunction. Current management of intestinal manifestations is largely
      inadequate. Patients with diarrhea are managed with low-fat diet, medium-chain
      triglycerides, avoidance of lactulose and fructose, and control of bacterial
      overgrowth with antibiotics for SIBO. In diarrhea/malabsorption, bile acid
      sequestrant and pancreatic enzyme supplementation may help, and nutritional
      support is needed. General measures are applied for constipation, and intestine
      rest plus antibiotics for pseudo-obstruction. Fecal incontinence is managed with
      measures for associated SIBO, or constipation, and with behavioral therapies.
      Pneumatosis intestinalis is usually an incidental finding that does not require
      any specific treatment. Immunomoduation should be considered early in intestinal
      involvement. Multidisciplinary approach of intestinal manifestations in SSc by
      gastroenterologists and rheumatologists is required for optimum management.

PMID- 29464585
TI  - A 19-Gauge Histology Needle Versus a 19-Gauge Standard Needle in Endoscopic
      Ultrasound-Guided Fine-Needle Aspiration for Solid Lesions: A Multicenter
      Randomized Comparison Study (GREATER Study).
AB  - BACKGROUND: The necessity of histological analysis is increasing. A 19-gauge
      histology needle (PC19) in endoscopic ultrasound-guided fine needle aspiration
      (EUS-FNA) has recently been developed and has shown high yields of tissue
      acquisition and histological diagnosis. AIMS: To compare the histological
      diagnostic yield in single-pass EUS-FNA for solid lesions using PC19 and a
      standard 19-gauge needle (EC19). PATIENTS AND METHODS: Consecutive patients with
      solid lesions were enrolled and underwent one pass with each of PC19 and EC19 for
      EUS-FNA with the randomized order of the needles. The primary endpoint was the
      histological diagnostic accuracy. The secondary endpoints were the feasibility,
      yield of histological core, cytological and overall diagnostic accuracies, and
      adverse events. Subgroup analysis was performed for the optimal situation with
      PC19. RESULTS: Of the 115 patients, 110 underwent EUS-FNA and five were excluded.
      EUS-FNA was performed from the esophagus in four, stomach in 80, or duodenum in
      26. The final diagnosis was malignancy in 100 and benign in 10. The feasibility
      was 98.2 and 97.3% with PC19 and EC19, respectively (p = 1.00). The rate of
      presence of a histological core and the histological, cytological, and overall
      diagnostic accuracies for PC19 versus EC19 were 84.6 versus 80.9% (p = 0.593),
      83.6 versus 73.6% (p = 0.099), 63.6 versus 56.4% (p = 0.335), and 90.0 versus
      79.1% (p = 0.039), respectively. PC19 was favored in the trans-esophageal/gastric
      approaches to obtain a histological diagnosis (p = 0.013). Adverse events were
      observed in four patients. CONCLUSION: Single-pass EUS-FNA with PC19 was feasible
      and showed significantly higher overall diagnostic accuracy and an increased
      tendency towards histological diagnostic accuracy, especially with trans
      esophageal/gastric FNA.

PMID- 29464588
TI  - Functional Meningeal Lymphatics and Cerebrospinal Fluid Outflow.
AB  - Functional meningeal lymphatic system plays a crucial role in outflow of
      cerebrospinal fluid. Metabolites and neurotoxins in the cerebrospinal fluid may
      be excreted via this system and accumulate in the cervical lymph nodes. In this
      letter, we highlighted the role of functional meningeal lymphatics and
      cerebrospinal fluid outflow.

PMID- 29464587
TI  - Comparison of the Effects of Vonoprazan and Lansoprazole for Treating Endoscopic
      Submucosal Dissection-Induced Artificial Ulcers.
AB  - BACKGROUND: Vonoprazan exhibits a more potent, rapid, and longer-lasting
      inhibitory effect on gastric acid secretion than proton pump inhibitors; however,
      whether it is more effective than PPI for treating endoscopic submucosal
      dissection (ESD)-induced artificial ulcers remains controversial. AIM: This study
      aimed to assess and compare the effects of vonoprazan and lansoprazole for
      treating ESD-induced artificial ulcers. METHODS: This prospective, randomized
      controlled trial enrolled 149 patients who underwent ESD for the treatment of
      early gastric neoplasms from April 2015 to May 2017. They were randomly treated
      with either 20 mg/day vonoprazan (V group) or 30 mg/day lansoprazole (L group)
      orally. The primary end points were the area and shrinkage ratio of the ulcers at
      4 and 8 weeks post-ESD. RESULTS: Data from 127 patients were analyzed, which
      showed that the 4- and 8-week healing ratios were not significantly different
      between the V and L groups (4 weeks, 16.3 vs. 25.8%; 8 weeks, 86.9 vs. 90.9%,
      respectively). Similarly, the shrinkage ratio, categorized as less than 90%, 90%
      or more but less than 100%, or 100% at 4 weeks and as less than 100% or 100% at 8
      weeks were not statistically different between the V and L groups (4 weeks: 12,
      41, 8 vs. 13, 41, 12, p = 0.7246; 8 weeks: 9, 52 vs. 9, 57, p = 0.8568). Delayed
      bleeding was also not significantly different between both the groups (5.4 vs.
      5.3%; p = 0.9844). CONCLUSIONS: Vonoprazan is as effective as lansoprazole in
      treating ESD-induced ulcers.

PMID- 29464589
TI  - Detection of Trypanosoma vivax DNA in semen from experimentally infected goats.
AB  - The present work aimed to investigate the presence of T. vivax DNA in the semen
      of experimentally infected goats. Twelve male goats native to the Brazilian
      Northeast, adults, were randomly assigned to two experimental groups: the
      infected group consisting of six goats infected intravenously with 0.5 mL of
      blood containing approximately 1.25 * 105 trypomastigotes of T. vivax, and a
      control group composed of six uninfected goats. After the infection, clinical
      examinations aiming to evaluate rectal temperature, parasitemia and hematocrit
      were performed. Semen samples were collected from goats by electroejaculation on
      the 7th, 14th and 21st days post-infection (dpi). The recombinant DNA-encoding
      gene encoding the L-like-specific gene for T. vivax. The infection was
      characterized by increased rectal temperature, high parasitemia and significant
      reduction of hematocrit values. Results for T. vivax DNA detection using TviCatL
      PCR were positive in all semen samples from the infected group collected on 7th,
      14th and 21st dpi. The presence of T. vivax DNA in 7th dpi suggests the early
      invasion of the parasite in the reproductive organs. Also, the finding of T.
      vivax DNA in all periods analyzed may suggest the continued elimination of the
      parasite in the semen, which may increase the chances of sexual transmission.
      Thus, T. vivax DNA is recorded for the first time in the semen of infected goats.
      Thus, these data are of great importance, since the detection of the T. vivax
      genetic material in the semen may point to the possibility that the parasite may
      be transmitted through the sexual pathway.

PMID- 29464590
TI  - Methods for the effective study of collective behavior in a radial arm maze.
AB  - Collective behaviors are observed throughout nature, from bacterial colonies to
      human societies. Important theoretical breakthroughs have recently been made in
      understanding why animals produce group behaviors and how they coordinate their
      activities, build collective structures, and make decisions. However,
      standardized experimental methods to test these findings have been lacking.
      Notably, easily and unambiguously determining the membership of a group and the
      responses of an individual within that group is still a challenge. The radial arm
      maze is presented here as a new standardized method to investigate collective
      exploration and decision-making in animal groups. This paradigm gives individuals
      within animal groups the opportunity to make choices among a set of discrete
      alternatives, and these choices can easily be tracked over long periods of time.
      We demonstrate the usefulness of this paradigm by performing a set of refuge-site
      selection experiments with groups of fish. Using an open-source, robust custom
      image-processing algorithm, we automatically counted the number of animals in
      each arm of the maze to identify the majority choice. We also propose a new index
      to quantify the degree of group cohesion in this context. The radial arm maze
      paradigm provides an easy way to categorize and quantify the choices made by
      animals. It makes it possible to readily apply the traditional uses of the radial
      arm maze with single animals to the study of animal groups. Moreover, it opens up
      the possibility of studying questions specifically related to collective
      behaviors.

PMID- 29464591
TI  - Design and Characterization of Topical Formulations: Correlations Between
      Instrumental and Sensorial Measurements.
AB  - The interaction between cosmetic emulsions and the skin's surface is an important
      factor to consider in the development of topical formulations. Two important
      ingredients in cosmetic formulations are waxes and polymers. The physical and
      mechanical properties of formulations directly impact the interface skin
      formulation. To evaluate this interaction, it is important to study the rheology,
      texture, and sensory properties. In this context, the aim of the study was to
      evaluate the influence of waxes and polymers on the rheological behavior, texture
      profile, and sensorial properties of topical formulations and the correlation
      between these parameters. The best combination of a wax and a polymer was
      determined by full factorial design of experiments and applied to develop eight
      formulations that were tested in relation to rheological, mechanical, and
      sensorial properties. The polymer helps with the spreadability of the
      formulation, and the wax had a strong influence on the parameters related to the
      structure of emulsions. A correlation between these parameters was observed. This
      way, it was possible to compare theoretical and practical data, except between
      the flow index and the work of shear. Finally, it was possible to predict
      sensorial aspects from rheological and texture parameters, making the formulation
      process easier and more integrated with all stages of the development of new
      topical formulations. Thus, the present study introduces a new proposal in the
      development of cosmetics.

PMID- 29464593
TI  - Improving Properties of Albendazole Desmotropes by Supramolecular Systems with
      Maltodextrin and Glutamic Acid.
AB  - Albendazole, an effective broad-spectrum anthelmintic agent, showed unpredictable
      therapeutic response caused by poor water solubility and slow dissolution rate.
      Then, novel binary and multicomponent supramolecular systems of two different
      solid forms of albendazole (I and II) with maltodextrin alone or with glutamic
      acid were studied as an alternative to improve the oral bioavailability of
      albendazole. The interactions and effects on the properties of albendazole were
      studied in solution and solid state. The solid systems were characterized using
      Raman and Fourier transform-infrared spectroscopy, thermal analysis, powder X-ray
      diffraction, and scanning electron microscopy. The solubility measurements,
      performed in aqueous and simulated gastric fluid, showed that albendazole (form
      II) was the most soluble form, while its supramolecular systems showed the
      highest solubility in simulated gastric fluid. On the other hand, the dissolution
      profiles of binary and multicomponent systems in simulated gastric fluid
      displayed pronounced increments of the dissolved drug and a faster dissolution
      rate compared to those of free albendazole forms. Thus, these supramolecular
      structures constitute an interesting alternative to improve the physicochemical
      properties of albendazole, with potential application for the preparation of
      pharmaceutical oral formulations.

PMID- 29464592
TI  - Delivery Considerations of Highly Viscous Polymeric Fluids Mimicking Concentrated
      Biopharmaceuticals: Assessment of Injectability via Measurement of Total Work
      Done "WT".
AB  - An account is given of the recent development of the highly viscous complex
      biopharmaceuticals in relation to syringeability and injectability. The specific
      objective of this study is to establish a convenient method to examine problem of
      the injectability for the needle-syringe-formulation system when complex
      formulations with diverse viscosities are used. This work presents the inter
      relationship between needle size, syringe volume, viscosity, and injectability of
      polymeric solutions having typical viscosities encountered in concentrated
      biologics, by applying a constant probe crosshead speed on the plunger-syringe
      needle assembly and continuously recording the force-distance profiles. A
      computerized texture analyzer was used to accurately capture, display, and store
      force, displacement, and time data. The force-distance curve and area under the
      curve are determined, and total work done for complete extrusion of the syringe
      content was calculated automatically by applying an established Matlab program.
      Various concentrations (i.e., 0.5-4% w/v of polymeric fluids/dispersions) of
      polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) with viscosity
      ranges of 5-100 cP mimicking concentrated monoclonal antibody solutions and
      complex biopharmaceutical formulations are investigated. Results indicate that
      calculated values of total work done to completely extrude the syringe content
      are the most appropriate parameter that describes viscosity-injection force of
      dispersed formulations. Additionally, the rheological properties of HPMC and PEO
      fluids in the context of syringeability and injectability are discussed.

PMID- 29464594
TI  - Inhalable Levofloxacin Liposomes Complemented with Lysozyme for Treatment of
      Pulmonary Infection in Rats: Effective Antimicrobial and Antibiofilm Strategy.
AB  - Treatment of bacterial infections becomes increasingly complicated due to
      increasing bacterial resistance and difficulty in developing new antimicrobial
      agents. Emphasis should be laid on improvising the existing treatment modalities.
      We studied the improved antimicrobial and antibiofilm activity of levofloxacin
      (LFX) and lysozyme (LYS) in microbiological studies. LFX at sub-minimum
      inhibitory concentration with LYS eradicated > 85% of preformed biofilm. LFX was
      actively loaded into the liposomes using pH gradient method and was spray-dried
      with LYS solution. Percent entrapment of LFX in liposome was > 80% and prolonged
      cumulative release of 85% LFX at the end of 12 h. In vitro lung deposition study
      and solid-state characterization for spray dried LFX liposome in combination with
      LYS (LFX liposome-LYS) was performed. Co-spray dried product had mass median
      aerodynamic diameter ranging < 5 MUm. In pharmacodynamic study, Staphylococcus
      aureus infected rats were treated with LFX liposome-LYS. Lungs, bronchoalveolar
      lavage fluid (BALF), and nasal fluid were evaluated for microbial burden.
      Expression of cytokine levels in BALF and serum were also studied by ELISA. In
      addition, mRNA expression for lung inflammatory mediators and lung
      myeloperoxidase activity were carried out. Further, lungs and histological
      changes were observed grossly. Untreated infected rat lungs demonstrated higher
      mRNA expression for inflammatory markers, cytokine levels, and microbial load
      compared to vehicle control. Conversely, LFX liposome-LYS significantly abated
      these adverse repercussions. Histology findings were also in agreement of above.
      Acute toxicity study revealed safeness of LFX liposome-LYS. Our findings confirm
      LFX liposome-LYS exhibited prolonged, improved antibiofilm and antimicrobial
      efficacy in treating S. aureus infection.

PMID- 29464595
TI  - Toxicological study of the degradation products of antineoplastic agent etoposide
      in commercial formulation treated by heterogeneous photocatalysis using SrSnO3.
AB  - Etoposide is an antineoplastic agent used for treating lung cancer, testicular
      cancer, breast cancer, pediatric cancers, and lymphomas. It is a pollutant due to
      its mutagenic and carcinogenic potential. Disposal of waste from this drug is
      still insufficiently safe, and there is no appropriate waste treatment.
      Therefore, it is important to use advanced oxidative processes (AOPs) for the
      treatment and disposal of medicines like this. The use of strontium stannate
      (SrSnO3) as a catalyst in heterogeneous photocatalysis reactions has emerged as
      an alternative for the removal of organic pollutants. In our study, SrSnO3 was
      synthesized by the combustion method and characterized by X-ray diffraction
      (XRD), Raman, UV-Vis, and scanning electron microscopy (SEM) techniques,
      obtaining a surface area of 3.28 m2 g-1 with cubic and well-organized
      crystallinity and a band gap of 4.06 eV. The experimental conditions optimized
      for degradation of an etoposide solution (0.4 mg L-1) were pH 5 and catalyst
      concentration of 1 g L-1. The results showed that the degradation processes using
      SrSnO3 combined with H2O2 (0.338 mol L-1) obtained total organic carbon removal
      from the etoposide solution, 97.98% (+/- 4.03 * 10-3), compared with TiO2, which
      obtained a mineralization rate of 72.41% (+/- 6.95 * 10-3). After
      photodegradation, the degraded solution showed no toxicity to zebrafish embryos
      through embryotoxicity test (OECD, 236), and no genotoxicity using comet assay
      and micronucleus test.

PMID- 29464596
TI  - Adsorptive removal of organics from aqueous phase by acid-activated coal fly ash:
      preparation, adsorption, and Fenton regenerative valorization of "spent"
      adsorbent.
AB  - Raw coal fly ash was activated to an adsorbent by sulfuric acid impregnation. The
      activation condition, the adsorption capacity, and the regenerative valorization
      of the adsorbent were studied. The results show that the optimal preparation
      conditions of the adsorbent are [H2SO4] = 1 mol L-1, activation time = 30 min,
      the ratio of coal fly ash to acid = 1:20 (g:mL), calcination temperature = 100 
      degrees C. The adsorption of p-nitrophenol on the adsorbent accords with the
      pseudo-second-order kinetic equation and the adsorption rate constant is 0.089 g
      mg-1 min-1. The adsorption on this adsorbent can be considered enough after 35
      min, when the corresponding adsorption capacity is 1.07 mg g-1 (85.6% of p
      nitrophenol removal). Compared with raw coal fly ash, the adsorbent has a stable
      adsorption performance at low pH range (pH = 1-6) and the adsorption of p
      nitrophenol is an exothermic process. Ninety minutes is required for the
      regenerative valorization of saturated adsorbent by Fenton process. The
      regenerative valorization for this saturated adsorbent can reach 89% under the
      optimal proposed conditions (30  degrees C, pH = 3, [H2O2] = 5.0 mmol L-1, [Fe2+]
      = 5.5 mmol L-1). Within 15 experimental runs, the adsorbent has a better and
      better stability with the increase of experimental runs. Finally, the mechanism
      of activating coal fly ash is proposed, being verified by the results of the SEM
      and BET test.

PMID- 29464597
TI  - The environmental Kuznets curve in the presence of corruption in developing
      countries.
AB  - Environmental degradation is at an alarming level in developing economies. The
      present paper examines the direct and indirect impacts of corruption on
      environmental deterioration using the panel data of 64 developing countries.
      Adopting the generalized method of moments (GMM) technique, the paper finds
      evidence that corruption exhibits a positive impact on pollution. Subsequently,
      there is also evidence indicating that the level of pollution tends to be higher
      in countries with a higher level of corruption, eliminating the effectiveness of
      income effect on environmental preservation. These results also suggest that
      environmental degradation is monotonically increasing with higher corruption and
      invalidate the presence of the EKC. Hence, a policy focuses that an anti
      corruption particularly in the environmental and natural resources sector needs
      to be emphasized and enforced in order to reduce or possibly to totally eliminate
      the rent for corruption.

PMID- 29464598
TI  - Ultrasound enhanced activation of peroxydisulfate by activated carbon fiber for
      decolorization of azo dye.
AB  - Activated carbon fiber (ACF) has become an emerging activator for peroxydisulfate
      (PDS) to generate sulfate radical (SO4*-). However, the relative low activation
      efficiency and poor contaminant mineralization limited its widespread
      application. Herein, ultrasound (US) was introduced to the ACF activated PDS
      system, and the synergistic effect of US and ACF in PDS activation and the
      enhancement of contaminant mineralization were investigated. The synergistic
      effect of US and ACF was observed in the PDS activation to decolorize orange G
      (OG). The decolorization efficiency increased with increasing ACF loading and US
      power, and PDS/OG ratio from 1 to 40. The activation energy was determined to be
      24.065 kJ/mol. The radical-induced decolorization of OG took place on the surface
      of ACF, and both SO4*- and hydroxyl radical (*OH) contributed to OG
      decolorization. The azo bond and naphthalene ring on OG were destructed to other
      aromatic intermediates and finally mineralized to CO2 and H2O. The introduction
      of US in the ACF/PDS system significantly enhanced the mineralization of OG. The
      combination of US and PDS was highly efficient to activate PDS to decolorize azo
      dyes. Moreover, the introduction of US remarkably improved the contaminant
      mineralization.

PMID- 29464599
TI  - Comparisons of cadmium bioaccumulation potentials and resistance physiology of
      Microsorum pteropus and Echinodorus grisebachii.
AB  - To better monitor and remediate environments contaminated by cadmium (Cd), plants
      are used as hyperaccumulators or biomonitors; however, few have been identified
      for aquatic Cd pollution. In our study, two aquatic ornamental plants, Microsorum
      pteropus (Blume) Copel. and Echinodorus grisebachii Small, were studied for their
      Cd accumulation capacity, morphological characteristics, and leaf physiological
      indexes. Microsorum pteropus (Blume) Copel. leaf has the potential to
      hyperaccumulate Cd (166 mg/kg dry weight for 1 mg/L exposure), with no
      significant physiological difference under exposure. Echinodorus grisebachii
      Small had sensitive diagnostic responses to Cd toxicity, such as significant
      decreases in Chl (a + b) and Chl-a/b, increased peroxidase (POD) activity,
      greater malondialdehyde (MDA) content, and increased soluble sugar content. These
      results suggest that Microsorum pteropus (Blume) Copel. could have the potential
      to be a Cd hyperaccumulator, while Echinodorus grisebachii Small could serve as a
      biomonitor for Cd-contaminated water bodies.

PMID- 29464600
TI  - Comparative study of calcium alginate, ball-milled biochar, and their composites
      on aqueous methylene blue adsorption.
AB  - In this work, a novel composite, ball-milled biochar (BMB) encapsulated in
      calcium-alginate (CA) beads (CA-BMB), was synthesized as an alternative adsorbent
      for the removal of methylene blue (MB) from an aqueous solution. Sorption
      performance was compared among CA, BMB, and CA-BMB composite with batch
      adsorption experiments. With 25% BMB and 75% alginate, the new composite
      resembled CA in MB adsorption. With an initial MB concentration of 50 mg L-1,
      kinetics studies showed that 74% MB removal by CA-BMB was achieved within 8 h,
      followed by slow kinetics reaching 91% removal in 16 h. The adsorption kinetics
      was well explained by the Ritchie's kinetic model, indicative of energetically
      heterogeneous solid surface of the composite. Adsorption isotherms of BMB, CA,
      and CA-BMB can all be fitted with the Langmuir models; the adsorption capacity of
      CA-BMB (1210.7 mg g-1) was close to that of CA (1282.2 mg g-1) and much higher
      than that of BMB alone (184.1 mg g-1). The outstanding adsorption performance
      suggested that CA-BMB can serve as a low-cost and eco-friendly adsorbent for MB
      removal from an aqueous solution.

PMID- 29464601
TI  - Using a multi-method approach based on soil radon deficit, resistivity, and
      induced polarization measurements to monitor non-aqueous phase liquid
      contamination in two study areas in Italy and India.
AB  - Geochemical and geophysical surveys employing radon deficit, resistivity, and
      induced polarization (IP) measurements were undertaken on soil contaminated with
      non-aqueous phase liquids (NAPLs) in two different sites in India and in Italy.
      Radon deficit, validated through the comparison with average soil radon in
      reference unpolluted areas, shows the extension of contamination in the upper
      part of the unsaturated aquifers. In site 1 (Italy), the spill is not recent. A
      residual film of kerosene covers soil grains, inhibiting their chargeability and
      reducing electrical resistivity difference with background unpolluted areas. No
      correlation between the two parameters is observed. Soil volatile organic
      compounds (VOCs) concentration is not linked with radon deficit, supporting the
      old age of the spillage. NAPL pollution in sites 2a and 2b (India) is more recent
      and probably still active, as demonstrated by higher values of electrical
      resistivity. A good correlation with IP values suggests that NAPL is still
      distributed as droplets or as a continuous phase in the pores, strengthening the
      scenario of a fresh spill or leakage. Residual fraction of gasoline in the pore
      space of sites 2a and 2b is respectively 1.5 and 11.8 kg per cubic meter of
      terrain. This estimation is referred to the shallower portion of the unsaturated
      aquifer. Electrical resistivity is still very high indicating that the gasoline
      has not been strongly degraded yet. Temperature and soil water content influence
      differently radon deficit in the three areas, reducing soil radon concentration
      and partly masking the deficit in sites 2a and 2b.

PMID- 29464602
TI  - Exploring the effects of earthworms on bacterial profiles during vermicomposting
      process of sewage sludge and cattle dung with high-throughput sequencing.
AB  - This study aims to reveal the effects of earthworms (Eisenia fetida) on bacterial
      profiles during the vermicomposting process of sewage sludge and cattle dung with
      the high-throughput sequencing technology. The earthworms could accelerate
      organic degradation and improve the stabilization process. Moreover, the addition
      of earthworms not only affected the bacterial numbers, but also increased the
      bacterial community diversity. The activity of earthworms had significant effects
      on the bacterial community structure as the bacterial community was clearly
      different between the vermicomposting and the control treatment. Furthermore, the
      earthworms affected the physical and chemical properties of substrates, thus
      promoting the growth of some microorganisms, such as Flavobacteria, Acidbacteria,
      and Planctomycetes. Earthworms largely inhibited the growth of various human
      pathogenic bacteria. In summary, earthworms significantly affected the bacterial
      community in vermicomposting and it could be applied as an authentically
      effective technique for the stabilization of organic wastes.

PMID- 29464603
TI  - Antioxidant biomarkers in Gammarus pulex to evaluate the efficiency of
      electrocoagulation process in landfill leachate treatment.
AB  - The discharge of landfill leachate into the environment without effective
      treatment poses a serious threat for the aquatic ecosystems. This present study
      was undertaken to evaluate whether electrocoagulation process is efficient for
      treatment landfill leachate (LL) or not by using antioxidant biomarkers in
      Gammarus pulex. Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and
      catalase (CAT) activities and malondialdehyde (MDA) and glutathione (GSH) levels
      in G. pulex exposed to untreated, treated, and diluted rates 1/10 and 1/20 in
      both LL during 24 and 96 h were tested. Physiochemical characteristics of
      leachate (chemical oxygen demand, electrical conductivity, pH, phosphate,
      turbidity, NH3, Cl-, and color) were determined pre and post treatment. All
      physiochemical characteristics of LL decreased after treatment process. GSH-Px
      and CAT activities and GSH and MDA levels were increased in untreated groups when
      compared to control (p < 0.05). After treatment by electrocoagulation, MDA and
      GSH levels and CAT activities were returned to control values. In conclusion, the
      abilities of LL to stimulate oxidative stress in G. pulex have been proven. The
      results revealed that antioxidant parameters are useful biomarkers for
      determining the treatment efficiency of the electrocoagulation process.

PMID- 29464604
TI  - Quantifying particulate matter accumulated on leaves by 17 species of urban trees
      in Beijing, China.
AB  - Airborne particulate matter (PM) has become a serious environmental problem and
      harms human health worldwide. Trees can effectively remove particles from the
      atmosphere and improve the air quality. In this study, a washing and weighing
      method was used to quantify accumulation of water-soluble ions and insoluble PM
      on the leaf surfaces and within the wax of the leaves for 17 urban plant species
      (including 4 shrubs and 13 trees). The deposited PM was determined in three size
      fractions: fine (0.2-2.5 MUm), coarse (2.5-10 MUm), and large (> 10 MUm).
      Significant differences in the accumulation of PM were detected among various
      species. The leaves of Platycladus orientalis and Pinus armandi were the most
      effective in capturing PM. Across the species, 65 and 35% of PM, on average,
      deposited on the leaf surface and in the wax, respectively. The greatest PM
      accumulation by mass on leaves was in the largest PM size fraction, while the
      accumulation of coarse and fine particle size fractions was smaller. Water
      soluble ions accumulated on the leaf surfaces contributed 28% to the total PM
      mass, on average. This study demonstrated that leaves of woody plants accumulate
      PM differently, and the most effective plant species should be selected in urban
      areas for attenuating ambient PM.

PMID- 29464606
TI  - Kinetics, isotherms, and thermodynamic studies of lead, chromium, and cadmium bio
      adsorption from aqueous solution onto Picea smithiana sawdust.
AB  - Lead (Pb), chromium (Cr), and cadmium (Cd) removal capacity of sawdust (Picea
      smithiana) from aqueous solution was investigated by conducting batch
      experiments. Thermodynamic parameters, like change in standard free energy
      (DeltaGTheta), enthalpy (DeltaHTheta) and entropy (DeltaSTheta) during bio
      adsorption process were estimated using the Van't Hoff equation. The maximum
      metals adsorption was observed at pH 8, 20 g L-1 bio-adsorbent and at 60 min of
      contact time. The metal adsorption kinetics was examined by fitting the pseudo
      first-order as well as four forms of pseudo-second-order kinetic models. Type 1
      pseudo-second-order equation described adsorption kinetics better than others.
      Langmuir model and Freundlich equations were used for calculation of sorption
      parameters. The Langmuir maximum adsorption capacity of Pb, Cr, and Cd was 6.35,
      3.37, and 2.87 mg g-1 at room temperature, respectively. The values of the
      separation factor (RL) were in between 0 and 1, indicating that bio-adsorption
      was favorable. Thermodynamics study revealed that the Pb, Cr, and Cd uptake
      reactions were endothermic and spontaneous. Results of the study asserted that
      the removal of heavy metal ions from aqueous solution is viable and the sawdust
      could be used in the treatment of effluents from industries, thereby reducing the
      level of water pollution.

PMID- 29464605
TI  - Polycyclic aromatic hydrocarbons (PAHs) in multi-phases from the drinking water
      source area of the Pearl River Delta (PRD) in South China: Distribution, source
      apportionment, and risk assessment.
AB  - Sixteen priority polycyclic aromatic hydrocarbons (PAHs) were investigated in the
      water dissolved phase (DP), suspended particulate matter (SPM), and sediment
      collected from the water source zone of the Pearl River Delta region. The sum of
      16 PAH concentrations ranged from 92.8 to 324 ng/L in the water DP, from 28.8 to
      205 ng/L in the SPM, and from 55.7 to 381 ng/g (d.w.) in the sediment. Compared
      with other areas globally, the PAH levels were considerably moderate in the DP
      and SPM and relatively low in the sediment. Spatial distribution of PAHs was site
      specific, and relatively higher PAH levels were found in the areas with dense
      population and heavy traffic. The PAH profile was dominated by two- and three
      ring PAHs, and PAH pollution was identified of pyrolytic origins. Based on risk
      quotient, the ecological risk in water was ranked as moderate, but the adverse
      health risk associated with water ingestion was minimal. Naphthalene and fluorene
      of the sediment samples showed potential biological impairment in some locations;
      nevertheless, the mean effects range median quotient suggested that the
      ecological risk of multiple PAHs was quite low (less than 10% incidence of
      adverse effects).

PMID- 29464608
TI  - [Tuberculosis in Germany - prevention, diagnosis, therapy].

PMID- 29464607
TI  - First report of an atypical new Aspergillus parasiticus isolates with nucleotide
      insertion in aflR gene resembling to A. sojae.
AB  - Aflatoxins are toxic and carcinogenic secondary metabolites produced primarily by
      the filamentous fungi Aspergillus flavus and Aspergillus parasiticus and cause
      toxin contamination in food chain worldwide. Aspergillus oryzae and Aspergillus
      sojae are highly valued as koji molds in the traditional preparation of fermented
      foods, such as miso, sake, and shoyu. Koji mold species are generally perceived
      of as being nontoxigenic and are generally recognized as safe (GRAS). Fungal
      isolates were collected from a California orchard and a few were initially
      identified to be A. sojae using beta-tubulin gene sequences blasted against NCBI
      data base. These new isolates all produced aflatoxins B1, B2, G1, and G2 and were
      named as Pistachio Winter Experiment (PWE) strains. Thus, it is very important to
      further characterize these strains for food safety purposes. The full length of
      aflR gene of these new isolates was sequenced. Comparison of aflR DNA sequences
      of PWE, A. parasiticus and A. sojae, showed that the aflatoxigenic PWE strains
      had the six base insertion (CTCATG) similar to domesticated A. sojae, but a pre
      termination codon TGA at nucleotide positions 1153-1155 was absent due to a
      nucleotide codon change from T to C. Colony morphology and scanning microscopic
      imaging of spore surfaces showed similarity of PWE strains to both A. parasiticus
      and A. sojae. Concordance analysis of multi locus DNA sequences indicated that
      PWE strains were closely linked between A. parasiticus and A. sojae. The finding
      documented the first report that such unique strains have been found in North
      America and in the world.

PMID- 29464609
TI  - ?

PMID- 29464610
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PMID- 29464615
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PMID- 29464616
TI  - [Non-invasive diagnosis of hepatocellular carcinoma].

PMID- 29464617
TI  - [Female genital mutilation in refugees].

PMID- 29464618
TI  - [Anaphylaxis].

PMID- 29464619
TI  - [Oxygen supplementation in respiratory failure].

PMID- 29464620
TI  - [Snoring and daytime sleepiness].

PMID- 29464621
TI  - [Interstitial lung disease - what the gereneral practitioner should know].

PMID- 29464622
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PMID- 29464655
TI  - GLP-1 Improves Diastolic Function and Survival in Heart Failure with Preserved
      Ejection Fraction.
AB  - Heart failure with preserved ejection fraction (HFpEF) has emerged as a public
      health burden with currently no effective medication. We assessed the treatment
      effects of the incretin hormone glucagon-like peptide-1 (GLP-1) on cardiac
      metabolism and function in a model of HFpEF. Following aortic banding, rats
      developed HFpEF characterized by diastolic dysfunction, pulmonary congestion, and
      poor survival (38%). A 4-week GLP-1 treatment via osmotic pumps significantly
      improved survival (70%) and reduced left ventricular stiffness, diastolic
      dysfunction, and pulmonary congestion. Isolated heart perfusion revealed
      preserved cardiac glucose oxidation (GO) and a shift in cardiac substrate
      utilization towards GO. While GLP-1 may boost insulin secretion and
      responsiveness, the protective effects were not related to cardiac insulin
      action. GLP-1 improves diastolic function and survival in rats with HFpEF, which
      was associated with a cardiac substrate switch towards GO. The therapeutic role
      of GLP-1 in HFpEF is new and warrants further investigation.

PMID- 29464656
TI  - Non-invasive Management Options for Erectile Dysfunction When a Phosphodiesterase
      Type 5 Inhibitor Fails.
AB  - Phosphodiesterase type 5 inhibitors (PDE5Is) are the drug of choice for medical
      management of erectile dysfunction (ED). On-demand PDE5Is have an overall
      efficacy of 60-70% for ED; 30-35% of patients fail to respond to a PDE5I, and 30
      50% of non-responders can be salvaged with detailed counseling on proper use and
      physician follow-up to ensure that the patient has been prescribed an appropriate
      and full PDE5I clinical trial. True non-responders may be offered intracavernosal
      injections of erectogenic drugs, intraurethral alprostadil, or surgical insertion
      of a penile prosthesis. Such options are not discreet and are associated with
      more adverse effects than PDE5Is. Thus patients may request additional non
      invasive medical management options. This review describes published literature
      on patients who failed to respond to an on-demand PDE5I regimen and were treated
      with a non-invasive PDEI-based regimen, including switching from one PDE5I to
      another; increasing the dose of PDE5I above the labeled dosage range; using two
      PDE5Is concurrently; using a daily PDE5I regimen; or combining a PDE5I with a
      testosterone supplement, alpha-adrenergic antagonist, intraurethral or
      intracavernosal alprostadil, vacuum erection device, or low-intensity shock wave
      therapy. The limitations of published clinical trials do not allow for sufficient
      evidence to recommend one option over another. Therefore, in PDE5I-refractory
      patients, the choice of a specific next step should be individualized based on
      the preference of the patient and his sexual partner, the advantages and
      disadvantages of the various options, the concurrent medical illnesses and
      medications of the patient, and the patient's response to treatment.

PMID- 29464657
TI  - Acute obstructive suppurative pancreatic ductitis (AOSPD) in pancreatic cancer
      treated by nasopancreatic drainage.
AB  - An 80-year-old woman with pancreatic cancer was admitted with fever and abdominal
      pain. Blood examinations showed an elevated CRP level. On computed tomography
      (CT), a pancreatic tumor with a dilated upstream main pancreatic duct (MPD) was
      seen. Endoscopic retrograde cholangiopancreatography (ERCP) showed the strictured
      part of the MPD at the head of the pancreas with upstream dilatation. A
      nasopancreatic drainage tube was placed. Through the tube, purulent pancreatic
      juice was discharged and culture of the pancreatic juice grew Klebsiella
      pneumoniae. On the day after ERCP, the patient's condition and the laboratory
      results improved. The patient's disorder was diagnosed as acute obstructive
      suppurative pancreatitis with pancreatic cancer.

PMID- 29464658
TI  - Examining the Association Between Different Aspects of Socioeconomic Status,
      Race, and Disability in Hawaii.
AB  - Socioeconomic status and race/ethnicity are known to be associated with health
      disparities. This study used data (2010-2014) from the American Community Survey.
      Respondents over age 30 from Hawaii were included (n = 44,921). Outcome variables
      were self-reported disability in vision, hearing, ambulatory function, self-care,
      independent living, or cognitive function. Four measures of socioeconomic status
      were personal income, average income for the area, income inequality for area,
      and education. This study used multivariable logistic regression to predict
      disability by race/ethnicity and socioeconomic status, controlling for age and
      gender. All four measures of socioeconomic status were significant predictors of
      at least one type of disability after adjustment for age, gender, and other
      measures of socioeconomic status. Higher education was significantly related to
      having every type of disability. Similarly, people with high personal income were
      less likely to have each type of disability than those with middle income, and
      those with low income were more likely to have all disabilities except hearing.
      Income inequality was significantly associated with half the disabilities. Low
      area income was significantly associated with increased vision-related
      disability, while high income was associated with less likelihood of hearing
      related disability. Native Hawaiians were significantly more likely to report
      having a disability than Filipinos and Chinese for all six types of disability,
      Japanese for four, and whites for two, after adjustment. These results suggest
      that in order to reduce health disparities for Native Hawaiians, as well as other
      ethnic groups, a range of socioeconomic factors need to be addressed.

PMID- 29464659
TI  - Embryonic Stem Cells in Development and Regenerative Medicine.
AB  - After progressive improvement in embryonic stem (ES) cell field, several studies
      have been conducted to explore the usage of ES cells in regenerative medicine.
      Unlimited self renewal and pluripoteny properties, combined with encouraging
      preclinical trials, remark that ES cell technology might be promising for
      clinical practice. ES cells, which can form three germ layers in vitro, are
      potential candidates to study development at the cellular and molecular level.
      Understanding the cell fate decision and differentiation processes during
      development might enable generating functional progenitor cells for tissue
      restoration. Progression in gene modifications and tissue engineering technology
      has facilitated the derivation of desired cells for therapy. Success in
      differentiation protocols and identification the regulatory pathways simplify the
      research for clinical applications. Although there are established protocols for
      cell differentiation in vitro and promising preclinical studies in vivo, many
      challenges need to be adressed before clinical translation. In this review, ES
      cells are discussed as a model of development in vitro and as a potential
      candidate for regenerative medicine. This review also dissusses current
      challenges for ES cell based therapy.

PMID- 29464661
TI  - An unusual cause of cavitating leukoencephalopathy: ethylmalonic encephalopathy.

PMID- 29464660
TI  - Association between vitamin D deficiency and risk of thyroid cancer: a case
      control study and a meta-analysis.
AB  - PURPOSE: Although vitamin D is reportedly associated with various cancers, the
      association between vitamin D and thyroid cancer is indefinite. We aimed to
      investigate whether this association applies to thyroid cancer (TC). METHODS: A
      total of 276 Chinese Han people were recruited in a current matched case-control
      study. Multivariable conditional logistic regression was computed to estimate the
      association between plasma 25(OH)D and papillary thyroid cancer (PTC). In
      addition, we searched relevant studies in PubMed and Web of Science databases
      before December 2017 to conduct a meta-analysis. RESULTS: In our case-control
      study, plasma 25(OH)D concentration was inversely associated with PTC risk
      (highest tertile vs lowest tertile: adjusted OR = 0.25; 95% CI 0.10, 0.61; Ptrend
      = 0.003). This association was independent of body mass index and physical
      activity (all adjusted Pinteraction > 0.05). A total of 11 studies were included
      in the meta-analysis, among which ten studies have been published and one was our
      case-control study. Compared with 25(OH)D non-deficient group, the pooled OR of
      TC was 1.42 (95% CI 1.17, 1.73) in the deficient group. Similarly, blood 25(OH)D
      levels in patients with TC were tend to be lower than those in the controls (SMD
      = - 0.20, 95% CI - 0.36, - 0.03). CONCLUSIONS: A high level of circulating
      25(OH)D was associated with a decreased TC risk. This association has important
      significance in public health and should, therefore, be further studied.

PMID- 29464662
TI  - Clinical routine assessment of palliative care symptoms and concerns and
      caregiver burden in glioblastoma patients: an explorative field study.
AB  - The implementation of self-reported outcome measurements into clinical routine
      was tested to help facilitate early access to palliative care (PC) for
      glioblastoma (GBM)-patients. Measures detail PC symptoms and concerns and
      caregiver burden. Between January 2014 and December 2016, a total of 337 GBM
      patients were discussed during meetings of the neuro-oncology tumor board to
      examine further treatment options. Each patient, along with their caregivers, was
      requested to participate in self-assessment using the palliative outcome scale
      (POS) and the Zarit Burden Interview (ZBI). Analyses encompassed summary
      statistics, non-parametric tests, visual graphic analysis, content analysis and
      assessing the utilization of the specialized PC consulting service (SPCCS).
      Ninety-five (28%) GBM-patients and 71 (21%) caregivers completed the self
      assessment. Of these, 20 patients and 12 caregivers repeated the assessment at
      least once more during follow-up. POS total scores were similar in the group of
      patients with initial diagnosis [10 (0-31)] and those with later disease stages
      like recurrent diagnosis [9 (0-25)], but ZBI total scores differed [14 (0-51) vs.
      24 (2-62)]. Single item analysis demonstrated that anxiety and worries about the
      future predominated. Caregivers were torn between high engagement in caring and
      feeling overburdened. Still, requests for the SPCCS showed no increase. Actual
      implementation of measures like POS and ZBI for detecting PC concerns and
      caregiver burden with GBM-patients in the field remains challenging as indicated
      by the limited response rate and lack of increased requests for the SPCCS.
      Modified clinical routines including strengthening awareness of PC, and allowing
      proxy-assessment might help to overcome barriers.

PMID- 29464663
TI  - Incidence and survival of gliomatosis cerebri: a population-based cancer
      registration study.
AB  - Gliomatosis cerebri (GC) comprises a rare widespread infiltrating growth pattern
      of diffuse gliomas. We explored the incidence patterns and survival rates of GC
      in a population-based registration sample from the Surveillance, Epidemiology and
      End, Results database (1973-2012). GC cases (n = 176) were identified based on
      their International Classification of Diseases in Oncology (ICD-O-3) morphology
      code (9381). We calculated age-adjusted incidence rates (AIR) and evaluated
      temporal trends. Survival was assessed with Kaplan-Meier curves and Cox
      regression models. The annual AIR of GC was 0.1/million. We noted increasing
      trends in the preceding registration years (1973-2002; annually, + 7%) and a
      tendency of clinical/radiological approaches to substitute the gold-standard
      histological assessment for diagnosis. GC was diagnosed in the entire age
      spectrum (range 1-98 years), but higher incidence rates (0.43/million) were noted
      among the elderly (>= 65 years). A slight male preponderance was identified (male
      to-female ratio: 1.4). Median overall survival was 9 months with a 5 year
      survival rate of 18%. Increasing age, primary tumor location not restricted to
      the cerebral hemispheres and rural residence at diagnosis were identified as
      negative prognostic factors, whereas receipt of radiotherapy, surgical treatment,
      race and method of diagnosis were not associated with outcome. This first
      comprehensive overview of GC epidemiology exemplifies the rarity of the disease,
      provides evidence for male preponderance and increased incidence among the
      elderly and shows lower survival rates compared to the published single center
      reports. Expansion of registration to histological and molecular characteristics
      would allow emergence of clinical prognostic factors at the population level.

PMID- 29464664
TI  - Benralizumab: First Global Approval.
AB  - Kyowa Hakko Kirin, AstraZeneca and subsidiaries are developing benralizumab
      (FasenraTM)-a humanised anti-interleukin-5 receptor alpha chain (IL-5Ralpha)
      monoclonal antibody-as a treatment of severe eosinophilic asthma and chronic
      obstructive pulmonary disease (COPD). Eosinophilia is a characteristic of certain
      asthma and COPD phenotypes and depletion of eosinophils has demonstrated
      therapeutic benefit. Benralizumab was recently approved by the US FDA as add-on
      maintenance therapy for patients with severe asthma who have an eosinophilic
      phenotype. This article summarizes the milestones in the development of
      benralizumab leading to this first approval for the treatment of severe
      eosinophilic asthma.

PMID- 29464665
TI  - Generic Substitution of Orphan Drugs for the Treatment of Rare Diseases:
      Exploring the Potential Challenges.
AB  - Generic drugs are important components of measures introduced by healthcare
      regulatory authorities to reduce treatment costs. In most patients and conditions
      the switch from a branded drug to its generic counterpart is performed with no
      major complications. However, evidence from complex diseases suggests that
      generic substitution requires careful evaluation in some settings and that
      current bioequivalence criteria may not always be adequate for establishing the
      interchangeability of branded and generic products. Rare diseases, also called
      orphan diseases, are a group of heterogeneous diseases that share important
      characteristics: in addition to their scarcity, most are severe, chronic, highly
      debilitating, and often present in early childhood. Finding a treatment for a
      rare disease is challenging. Thanks to incentives that encourage research and
      development programs in rare diseases, several orphan drugs are currently
      available. The elevated cost of orphan drugs is a highly debated issue and a
      cause of limited access to treatment for many patients. As patent protection and
      the exclusivity period of several orphan drugs will expire soon, generic versions
      of orphan drugs should reach the market shortly, with great expectations about
      their impact on the economic burden of rare diseases. However, consistent with
      other complex diseases, generic substitution may require thoughtful
      considerations and may be even contraindicated in some rare conditions. This
      article provides an overview of rare disease characteristics, reviews reports of
      problematic generic substitution, and discusses why generic substitution of
      orphan drugs may be challenging and should be undertaken carefully in rare
      disease patients.

PMID- 29464666
TI  - Application of Discrete-Choice Experiment Methods in Tobacco Control: A
      Systematic Review.
AB  - BACKGROUND: Economic evidence relating to tobacco control is generally derived
      from the cost effectiveness of smoking-cessation programs or the economic impact
      of tobacco-induced disease, based on revealed-preference data. However, empirical
      estimates from stated-preference data on tobacco users' preferences, smoking
      behaviour and smoking cessation aids using analytical techniques such as discrete
      choice experiments (DCEs) could be important for policy decision making in
      tobacco control. OBJECTIVES: Our objective was to review the practice and utility
      of DCE methodology across nicotine- and tobacco-related issues, particularly
      smoking and smoking-cessation behaviour, anti-smoking policies and preferences
      for smoking-cessation aids. METHODS: We searched the PubMed, MEDLINE and ECONLIT
      databases for full-text original research articles on tobacco-related issues
      published between January 2000 and April 2016 that used a DCE method. We
      summarised the evidence and methodological characteristics of DCEs according to
      Lancsar and Louviere, 2008. RESULTS: Our review of the 12 eligible studies showed
      that DCE methodology was used to elicit smoker preferences and to evaluate
      tobacco-control policies. The majority of the studies were published in the last
      5 years. The areas of application were smoking cessation, smoking behaviour,
      electronic cigarette use, water-pipe smoking and tobacco packaging. Monetary
      attributes were the most influential attributes in all studies. The design of the
      DCEs varied. CONCLUSION: DCE studies of tobacco-related issues were
      methodologically consistent with guidelines proposed for conducting health
      related DCEs.

PMID- 29464667
TI  - Economic Evaluation of Bevacizumab for Treatment of Platinum-Resistant Recurrent
      Ovarian Cancer in Canada.
AB  - BACKGROUND: Ovarian cancer is a leading cause of cancer-related mortality.
      Although the disease is relatively rare, it carries a disproportionately large
      morbidity burden. OBJECTIVE: We conducted a cost-utility analysis from a Canadian
      public payer perspective to determine the cost effectiveness of bevacizumab, a
      newly available treatment option for recurrent ovarian cancer. METHODS: Using a 7
      year time horizon, a three health-state cohort-based partitioned survival model
      was developed to assess the cost utility of bevacizumab plus chemotherapy (BEV)
      versus chemotherapy alone. We reconstructed individual patient data from
      published Kaplan-Meier curves. Clinical parameters, including progression-free
      survival and overall survival, were derived from the AURELIA phase III randomized
      controlled trial. Costs, resource utilization and utility values from recent
      Canadian sources were used to populate the model. Results were presented using
      incremental cost-utility ratios (ICURs). Uncertainty was examined through
      univariate and probabilistic sensitivity analyses. RESULTS: The reconstructed
      individual patient data matched the AURELIA trial results. Total costs for the
      BEV and chemotherapy treatment arms were $Can79,086 and $Can54,982, respectively.
      Total estimated quality-adjusted life-years (QALYs) were 1.1055 and 0.9926 for
      the BEV and chemotherapy arms, respectively. The ICUR was estimated to be
      $Can213,424 per QALY gained. At a willingness-to-pay threshold of $Can100,000 per
      QALY gained, the probability of BEV being cost effective was 0. CONCLUSIONS: The
      results of our analysis suggest that the addition of bevacizumab to single-agent
      chemotherapy treatment, while improving patient outcomes, is unlikely to be cost
      effective in this Canadian patient population. The results also provide some
      preliminary validation for use of individual patient data-reconstruction
      techniques in pharmacoeconomic evaluation.

PMID- 29464668
TI  - Health Technology Assessment for Policy Making in India: Current Scenario and Way
      Forward.

PMID- 29464669
TI  - Weighting Health Outcomes by Socioeconomic Position Using Stated Preferences.
AB  - BACKGROUND: The trade-off that society is willing to make to promote a more
      equitable distribution of health can be represented as a social welfare function
      (SWF). SWFs are an economic construct that can be used to illustrate concerns for
      total health with aversion to inequalities between socioeconomic groups.
      OBJECTIVE: This study used people's preferences to estimate the shapes of health
      related SWFs (HRSWFs). We tested the suitability of this method to derive equity
      weights. METHODS: A questionnaire was used to elicit preferences concerning trade
      offs between the total level of health and its distribution among two
      socioeconomic groups. The participant group was a sample of convenience that
      included a mix of health researchers, academics, clinicians, managers, public
      servants and research students. The data collected were used to develop HRSWFs
      with a constant elasticity of substitution. The weight was calculated using the
      marginal rate of substitution. RESULTS: A marginal health gain to the lowest
      socioeconomic position (SEP) group was valued 14.1-81.4 times more than a
      marginal health gain to the high SEP group. CONCLUSIONS: Our results provide
      evidence to support the idea that the public may be willing to make trade-offs
      between efficiency and equity, and that they value health gains differently
      depending on which socioeconomic group receives the health gain. Further evidence
      is required before such indicative weights have practical value.

PMID- 29464670
TI  - Reliability and Validity of the Greek Migraine Disability Assessment (MIDAS)
      Questionnaire.
AB  - BACKGROUND: The Migraine Disability Assessment (MIDAS) Questionnaire is a
      reliable and valid instrument for migraine-related disability. Such a tool is
      needed to quantify migraine-related disability in the Greek population.
      OBJECTIVE: This validation study aims to assess the test-retest reliability,
      internal consistency, item discriminant and convergent validity of the Greek
      translation of the MIDAS. METHODS: Adults diagnosed with migraine completed the
      MIDAS Questionnaire on two occasions 3 weeks apart to assess reliability, and
      completed the RAND-36 to assess validity. RESULTS: Participants (n = 152) had a
      median MIDAS score of 24 and mostly severe disability (58% were grade IV). The
      test-retest reliability analysis (N = 59) revealed excellent reliability for the
      total score. Internal consistency was alpha = 0.71 for initial and alpha = 0.82
      for retest completion. For item discriminant validity, the correlations between
      each question and the total score were significant, with high correlations for
      questions 2-5 (range 0.67 <= r <= 0.79; p < 0.01). For convergent validity, there
      was significant negative correlation between the total score and all RAND-36
      subscales except for 'emotional wellbeing'. The negative correlation indicates
      that patients with a lower degree of disability according to their MIDAS score
      tended to have better wellbeing. Psychometric properties are comparable with
      those of other published validation studies of the MIDAS and the original.
      Findings on question 1 show that missing work/school days may be closely related
      with increased affect issues. CONCLUSION: The Greek version of the MIDAS
      Questionnaire has good reliability and validity. This study allowed for cross
      cultural comparability of research findings.

PMID- 29464671
TI  - An Exploratory Study of Long-Term Publicly Waitlisted Bariatric Surgery Patients'
      Quality of Life Before and 1 Year After Bariatric Surgery, and Considerations for
      Healthcare Planners.
AB  - BACKGROUND: Long-term publicly waitlisted bariatric surgery patients typically
      experience debilitating physical/psychosocial obesity-related comorbidities that
      profoundly affect their quality of life. OBJECTIVES: We sought to measure quality
      of-life impacts in a study population of severely obese patients who had
      multiyear waitlist times and then underwent bariatric surgery. METHODS:
      Participants were recruited opportunistically following a government-funded
      initiative to provide bariatric surgery to morbidly obese long-term waitlisted
      patients. Participants self-completed the EQ-5D-5L and AQoL-8D questionnaires pre
      and postoperatively. Utility valuations (utilities) and individual/super
      dimension scores (AQoL-8D only) were generated. RESULTS: Participants' (n = 23)
      waitlisted time was mean [standard deviation (SD)] 6.5 (2) years, body mass index
      reduced from 49.3 (9.35) kg/m2 preoperatively to 40.8 (7.01) 1 year
      postoperatively (p = 0.02). One year utilities revealed clinical improvements
      (both instruments). AQoL-8D improved significantly from baseline to 1 year, with
      the change twice that of the EQ-5D-5L [EQ-5D-5L: mean (SD) 0.70 (0.25) to 0.78
      (0.25); AQoL-8D: 0.51 (0.24) to 0.67 (0.23), p = 0.04], despite the AQoL-8D's
      narrower algorithmic range. EQ-5D-5L utility plateaued from 3 months to 1 year.
      AQoL-8D 1-year utility improvements were driven by Happiness/Coping/Self-worth (p
      < 0.05), and the Psychosocial super dimension score almost doubled at 1 year (p <
      0.05). AQoL-8D revealed a wider dispersion of individual utilities. CONCLUSIONS:
      Ongoing improvements in psychosocial parameters from 3 months to 1 year post
      surgery accounted for improvements in overall utilities measured by the AQoL-8D
      that were not detected by EQ-5D-5L. Selection of a sensitive instrument is
      important to adequately assess changes in quality of life and to accurately
      reflect changes in quality-adjusted life-years for cost-utility analyses and
      resource allocation in a public healthcare resource-constrained environment.

PMID- 29464672
TI  - Assessing Variation in the Cost of Palivizumab for Respiratory Syncytial Virus
      Prevention in Preterm Infants.
AB  - BACKGROUND: The variability in cost of palivizumab treatment, indicated for
      prevention of respiratory syncytial virus (RSV) infections in high-risk infants,
      has not been robustly estimated in prior studies. This study aimed to determine
      the cost variations of palivizumab from a US payer perspective for otherwise
      healthy preterm infants born 29-35 weeks gestational age (wGA) using infant
      characteristics and applied dosing regimens. METHODS: Fenton Growth Charts were
      merged with World Health Organization Child Growth Standards to estimate preterm
      infant growth patterns. The merged growth chart was applied to infants who
      received palivizumab from a prospective, observational registry to determine
      future body weight using each infant's wGA and birth weight. Using quarter 3 (Q3)
      2016-Q2 2017 vial cost, treatment costs at monthly dosing intervals were
      estimated using expected weights and averaged by age to derive expected mean 2016
      2017 RSV seasonal costs per infant under various dosing scenarios. RESULTS: Given
      different dosing scenarios (two to five doses), birth month, and growth patterns
      for preterm infants 29-35 wGA, the estimated average 2016-2017 seasonal cost of
      palivizumab treatment ranged from $3221 to $12,568. Outpatient-only cost
      (excluding first dose at hospital discharge) ranged from $1733 to $11,862. The
      main drivers of costs were dosing regimen (74% of variance), dosing interacted
      with birth month (17%), and wGA (6%). CONCLUSION: The considerable variability in
      the average cost of palivizumab treatment for preterm infants is driven by choice
      of dosing regimen, wGA, and birth month. Therefore, when estimating the cost of
      palivizumab, it is important to consider both infant characteristics at each dose
      and potential dosing regimens.

PMID- 29464673
TI  - Comparison of Disease-Modifying Therapies for the Management of Multiple
      Sclerosis: Analysis of Healthcare Resource Utilization and Relapse Rates from US
      Insurance Claims Data.
AB  - BACKGROUND: Data on comparative healthcare resource utilization and costs
      associated with the newer oral disease-modifying therapies (DMTs) for managing
      relapsing-remitting multiple sclerosis (MS) in routine clinical practice are
      limited. The purpose of this study was to estimate healthcare resource
      utilization, costs, and relapse rates in the year after initiating treatment with
      dimethyl fumarate (DMF), interferon (IFN)-beta, glatiramer acetate (GA),
      teriflunomide, or fingolimod in routine clinical practice for patients with MS
      who did not receive a DMT in the previous year. METHODS: Patients initiating DMF,
      IFNbeta, GA, teriflunomide, or fingolimod were identified based on claims data
      from 2012 to 2015 in the Truven MarketScan Commercial Claims Databases (n =
      4194). Healthcare resource utilization assessment included the proportion of
      patients who were hospitalized, or had emergency room (ER) or urgent care (UC)
      visits. Healthcare costs were estimated for 1 year before and 1 year after DMT
      initiation. Relapse episodes were identified based on a published claims-based
      algorithm and clinical input from the research investigators. RESULTS: After DMT
      initiation, significant reductions in the proportions of patients who were
      hospitalized or requiring ER/UC visits were observed in all patient cohorts (p <
      0.001 and p < 0.05, respectively). Non-prescription medical costs decreased after
      DMT initiation, with the largest decrease observed in the DMF cohort (US$5761
      reduction, p < 0.0001). Reductions in non-prescription medical costs were
      associated with decreased use of outpatient services and inpatient hospital
      stays, and have the potential to partially offset DMT costs. CONCLUSIONS: DMT
      initiation is associated with reductions in healthcare resource utilization and
      non-prescription medical costs in routine clinical practice.

PMID- 29464674
TI  - Attention toward contexts modulates context-specificity of behavior in human
      predictive learning: Evidence from the n-back task.
AB  - According to the attentional theory of context processing (ATCP), learning
      becomes context specific when acquired under conditions that promote attention
      toward contextual stimuli regardless of whether attention deployment is guided by
      learning experience or by other factors unrelated to learning. In one experiment
      with humans, we investigated whether performance in a predictive learning task
      can be brought under contextual control by means of a secondary task that was
      unrelated to predictive learning, but supposed to modulate participants'
      attention toward contexts. Initially, participants acquired cue-outcome
      relationships presented in contexts that were each composed of two elements from
      two dimensions. Acquisition training in the predictive learning task was combined
      with a one-back task that required participants to match across consecutive
      trials context elements belonging to one of the two dimensions. During a
      subsequent test, we observed that acquisition behavior in the predictive learning
      task was disrupted by changing the acquisition context along the dimension that
      was relevant for the one-back task, while there was no evidence for context
      specificity of predictive learning when the acquisition context was changed along
      the dimension that was irrelevant for the one-back task. Our results support the
      generality of the principles advocated by ATCP.

PMID- 29464675
TI  - Outpatient parenteral antibiotic therapy in a suburban tertiary referral centre
      in Australia over 10 years.
AB  - PURPOSE: Outpatient parenteral antibiotic therapy (OPAT) is a widely accepted and
      safe therapeutic option for carefully selected patients. This study reviewed the
      practice of an OPAT service in a large Australian tertiary teaching hospital in
      Western Sydney over a 10-year period. METHOD: Data were retrieved from a
      prospectively maintained electronic database which included information on
      patient demographics, clinical diagnosis, microbiological identity, antimicrobial
      therapy, complications and readmissions. Data were analysed using descriptive
      statistics. RESULTS: There were 3435 referrals made to the service between
      January 2004 and June 2014, amounting to 25,289 antibiotic days. The most
      frequent referral was for Skin and Soft Tissue Infections (SSTIs), 61.28%,
      followed by Bone and Joint Infections (BJIs), 15.30%. The most common organism
      identified was methicillin-sensitive Staphylococcus aureus. Readmission was
      uncommon (5.15%), with the highest rate of readmission noted for Cardiovascular
      System Infections (16.67%) followed by BJIs (10.31%). Line infection, aseptic
      thrombophlebitis and drug hypersensitivity or reaction were the cause of 68.55%
      of all complications. There was a decline in line-related complications
      throughout the study period. CONCLUSION: OPAT service is in increasing demand in
      Australia, providing a significant relief in in-hospital days. Growth in
      referrals was seen not only with SSTIs and BJIs, but also a diverse range of
      other infective entities with limited literature in its treatment in an OPAT
      setting. This study highlights the need to improve data collection, develop risk
      stratification strategies and standardisation of OPAT services in Australia.

PMID- 29464676
TI  - Further Evidence of the Association of the Diacylglycerol Kinase Kappa (DGKK)
      Gene With Hypospadias.
AB  - PURPOSE: Hypospadias is a common developmental anomaly of the male external
      genitalia. In previous studies conducted on West European, Californian, and Han
      Chinese populations the relationship between polymorphic variants of the
      diacylglycerol kinase kappa (DGKK) gene and hypospadias have been reported. The
      aim was to study the possible associations between polymorphic variants of the
      DGKK gene and hypospadias using an independent sample of the Polish population.
      MATERIALS AND METHODS: Ten single nucleotide polymorphisms in DGKK, which were
      reported to have an impact on the risk of hypospadias in other populations, were
      genotyped using high-resolution melting curve analysis in a group of 166 boys
      with isolated anterior (66%) and middle (34%) forms of hypospadias and 285
      properly matched controls without congenital anomalies. RESULTS: Two DGKK
      variants rs11091748 and rs12171755 were associated with increased risk of
      hypospadias in the Polish population. These results were statistically
      significant, even after applying the Bonferroni correction for multiple
      comparisons (P < .005). All the tested nucleotide variants were involved in
      haplotype combinations associated with hypospadias. The global p-values for
      haplotypes comprising of rs4143304-rs11091748, rs11091748-rs17328236, rs1934179
      rs4554617, rs1934183-rs1934179-rs4554617 and rs12171755-rs1934183-rs1934179
      rs4554617 were statistically significant, even after the permutation test
      correction. CONCLUSION: Our study provides strong evidence of an association
      between DGKK nucleotide variants, haplotypes and hypospadias susceptibility.

PMID- 29464677
TI  - Laparoscopic Pyelolithotomy for Management of Complete Staghorn Stone of An
      Ectopic Pelvic Kidney.
AB  - A 40-year-old man was referred to our urology clinic due to vague abdominal pain
      and hematuria. Computed tomography (CT) without contrast material visualized an
      ectopic kidney in the left iliac fossa with a complete staghorn stone. Under
      general anesthesia, operation was done in supine position with a gentle lateral
      elevation on the right side. The surgeon stands on the right side of the patient.
      First, a 12 mm port was inserted at the umbilicus using the Hasson technique.
      After creation of pneumoperitoneum, operation was done by three 5 mm trocars were
      arranges as paraumbilical, the point between umbilicus and inguinal canal at left
      and right side.A vertical pyelotomy incision was made over the anterior pelvic
      wall and then extended to a cross figure. The stone extracted intact with a
      laparoscopic stone grasper and placed in endobag. A short double J stent was
      placed via the pyelotomy incision and renal pelvis was closed using continuous
      4.0 vicryl sutures. He was discharged from hospital after 3 days without any
      complication.

PMID- 29464678
TI  - Reconstruction of an Incompletely Amputated Penis with The Radical Penile Crural
      Dissection and Radial Forearm Free Flap.

PMID- 29464679
TI  - Prognostic significance of body mass index and other tumor and patient
      characteristics in non-metastatic renal cell carcinoma.
AB  - PURPOSE: In this retrospective study, we aimed to investigate the prognostic
      effect of body mass index (BMI) in localized renal cell carcinoma (RCC) cases who
      underwent surgical treatment. Furthermore, the assessment of various patient and
      tumor characteristics and surgical methods on survival has been identified as
      additional targets. MATERIALS AND METHODS: Three hundred and eighty patients with
      localised, non-metastatic, unilateral RCC who underwent radical or partial
      nephrectomy in our clinic between January 2007 and December 2016 were enrolled in
      this study. Age, gender, height, weight, BMI, operation type and method,
      pathology results and tumor stage of the patients were recorded. Patients were
      divided into 3 groups according to body mass index (BMI): Normal weight(< 25
      kg/m2), overweight (25-30 kg/m2) and obese (>30 kg/m2) as groups 1, 2 and 3,
      respectively. We analyzed the relation between the BMI, gender, smoking,
      hypertension, type and method of surgical treatment, histologic subtype, tumor
      stage, estimated glomerular filtration rate (eGFR) and cancer-specific (CSS) and
      recurrence free survival (RFS). All data analysis was performed using SPSS(r)
      Statistical Software for Windows (Version 13.0) and a P value less than 0.05 was
      considered to be significant. RESULTS: The effect of BMI on both CSS and RFS was
      statistically significant (P < .001). There was also a significant relation
      between smoking, operation type (partial/radical), eGFR and tumor stage and CSS
      and RFS. CONCLUSION: Our findings show that overweight and obese RCC patients
      according to the BMI have a more favorableprognosis. Multicenter, prospective
      studies with more cases and longer oncological follow-up period are needed to
      support these findings.

PMID- 29464680
TI  - Comparative Results of Transurethral Incision with Transurethral Resection of The
      Prostate in Renal Transplant Recipients with Benign Prostate Hyperplasia.
AB  - PURPOSE: The aim of this study is to compare the results of transurethral
      incision of the prostate (TUIP) and transurethral resection of the prostate
      (TURP) for the surgical treatment of benign prostate hyperplasia (BPH) in
      patients with renal transplantation. MATERIALS AND METHODS: Between April 2009
      and May 2016, BPH patients with renal transplants whose prostate volumes were
      less than 30 cm3 were treated surgically. Forty-seven patients received TURP and
      32 received TUIP. The patients' age, duration of dialysis, duration between
      transplant and TURP/TUIP, preoperative and postoperative serum creatinine (SCr),
      International Prostate Symptom Score (IPSS), maximum flow rate (Qmax) and
      postvoidresidual volume (PVR) were recorded. At 1-,6- and 12-month follow-up,
      early and long-term complications were assessed. Results were evaluated
      retrospectively. RESULTS: In both groups, SCr, PVR and IPSS decreased
      significantly after the operation, while Qmax increased significantly (P < .001).
      There was no difference between the two groups in terms of increase in Qmax and
      decrease in IPSS, SCr and PVR (P = .89, P = .27, P = .08, and P = .27). Among
      postoperative complications, urinary tract infection (UTIs) and retrograde
      ejaculation (RE) rates were higher in the TURP group than the TUIP group (12.7%
      versus 6.2% and 68.1% versus 25%,respectively), whereas urethral strictures were
      more prevalent in the TUIP group (12.5% versus 6.3%). CONCLUSION: For the
      treatment of BPH in renal transplant patients with a prostate volume less than 30
      cm3, bothTUIP and TURP are safe and effective.

PMID- 29464681
TI  - An Unusual Complication of Suprapubic Catheter Migration into the Left Ureter.
AB  - Suprapubic cystostomy is a widely employed procedure that is used to drain the
      bladder. Despite being a safe procedure, suprapubic cystostomy has been reported
      to present multiple intra- and postoperative complications. Serious and unusual
      complications can occur during changing of the suprapubic catheter (SPC) in
      patients with neuropathic bladder. In this work, we report an elderly patient
      with neuropathic bladder suffering from an unusual complication involving
      migration of the SPC into the ureter during changing of the SPC, leading to
      ureteric obstruction and left pyelonephritis.

PMID- 29464682
TI  - Comparison of Partial and Radical Laparascopic Nephrectomy: Long-Term Outcomes
      for Clinical T1b Renal Cell Carcinoma.
AB  - PURPOSE: To compare the long-term clinical and oncologic outcomes in patients
      treated with laparoscopic partial nephrectomy (LPN) and laparoscopic radial
      nephrectomy (LRN) for clinical T1b renal cell carcinoma. MATERIALS AND METHODS:
      We retrospectively reviewed the records of all patients who underwent LPN or LRN
      for a single clinical T1b tumor between January 2005 and January 2012, an actual
      follow-up of 2-year or greater was available in 39 and 160 after LPN and LRN,
      respectively. Survival was calculated using the Kaplan-Meier method.
      Multivariable Cox regression analysis was done to assess predictors of survival.
      RESULTS: The two cohorts of patients were similar in age, sex, body-mass index
      and preoperative eGFR. There were no differences in tumors size (4.97 vs 5.29cm,
      P = .08), and pathological stage distribution between the two cohorts. The median
      follow-up after LPN and LRN were 67 (range: 18-118) and 70 (19-120) months,
      respectively. For LPN versus LRN, 5-years overall and cancer specific survival
      rates were 93.33% vs 85.69% and 96.00% vs 91.35%, respectively. For LPN versus
      LRN, 10-years overall and cancer specific survival rates were 85.56% vs73.41% and
      88.00% vs 82.85%, respectively. On multivariate analysis, patients' age, ASA
      score and pathological stage were the major factors affecting overall survival,
      and patients' age and pathological stage were associated with cancer specific
      survival. The percent decrease in glomerular filtration rate was significantly
      lower in the LRN group at early and last followup. CONCLUSION: LPN is an
      effective treatment option in appropriately selected patients with cT1b RCC. It
      provides 5-year, 10-year overall survival and cancer specific survival comparable
      to those of LRN as well as better preservation of renal function than LRN.
      Overall survival and cancer specific survival are associated with nonmodifiable
      factors but not by the choice of operative technique.

PMID- 29464683
TI  - Autophosphorylation of the carboxyl-terminal domain is not required for oncogenic
      transformation by lung-cancer derived EGFR mutants.
AB  - Aberrant activation of cancer-derived mutants of the epidermal growth factor
      receptor (EGFR) is closely associated with cancer pathogenesis and is thought to
      be mediated through multiple tyrosine phosphorylations within the C-terminal
      domain. Here, we examined the consequences of the loss of these C-terminal
      phosphorylation sites on cellular transformation in the context of lung-cancer
      derived L858R, exon 19 deletion and exon 20 insertion mutant EGFR. Oncogenic EGFR
      mutants with substitution of the 10 potential C-terminal tyrosine
      autophosphorylation sites for phenylalanine (CYF10) were still able to promote
      anchorage-independent growth in soft agar at levels comparable to the parental
      L858R or exon19 deletion or exon 20 insertion mutants with intact
      autophosphorylation sites. Furthermore, these CYF10 mutants retained the ability
      to transform Ba/F3 cells in the absence of IL-3. Bead-based phosphorylation and
      immunoprecipitation analyses demonstrated that key EGFR-associated proteins
      including Grb2 and PLC-gamma-are neither phosphorylated nor bound to CYF10
      mutants in transformed cells. Taken together, we conclude that tyrosine
      phosphorylation is not required for oncogenic activity of lung-cancer-derived
      mutant EGFR, suggesting these mutants can lead to cellular transformation by an
      alternative mechanism independent of EGFR phosphorylation.

PMID- 29464685
TI  - Estimating Sex Using Metric Analysis of the Scapula by Postmortem Computed
      Tomography.
AB  - Postmortem computed tomography (CT) has been extensively used in the last decade
      for identification purposes and in various anthropologic studies. Postmortem CT
      measurements of scapulae, analyzed using logistic discriminant function developed
      in this study, showed 94.5% accuracy in estimating sex. Data analyzed using the
      Dabbs and Moore-Jansen (2010) discriminant function and the discriminant function
      generated in this study provided nearly identical results with disagreement in
      only one case. Height and weight were not statically significant in sex
      prediction. The results of this study show that data obtained from volume
      rendered postmortem CT images can be considered reliable and treated as a
      practical option to standard anthropological methods, especially in mass
      fatalities as a rapid triage tool for sex determination.

PMID- 29464686
TI  - Fatal Complications of Aesthetic Techniques: The Gluteal Region.
AB  - Cosmetic procedures are common and utilize many techniques to obtain
      aesthetically good outcomes for patient satisfaction with acceptable safety
      standards. Cosmetic procedures that involve the gluteal region are becoming
      increasingly popular as various procedures can target the gluteal region such as
      liposuction, tumescent liposuction, cosmetic filler injections, autologous fat
      transfer, depot drug delivery, and implants. Complications of cosmetic gluteal
      procedures can be localized or systemic with systemic complications being
      responsible for most deaths. These reported systemic complications include
      sepsis, thromboembolism, fat embolism with or without fat embolism syndrome,
      macroscopic fat embolism, anesthesia-related and blood volume abnormalities. We
      herein report 10 deaths due to elective gluteal cosmetic procedures. Autologous
      fat transfer (fat grafting, lipoinjection) following liposuction resulted in 8 of
      10 fatal outcomes of the gluteal aesthetic procedures. A comprehensive discussion
      of gluteal anatomy, gluteal contouring procedures, and the approach to such cases
      is presented along with the autopsy findings of the reported cases.

PMID- 29464684
TI  - Neuregulin directed molecular mechanisms of visual cortical plasticity.
AB  - Experience-dependent critical period (CP) plasticity has been extensively studied
      in the visual cortex. Monocular deprivation during the CP affects ocular
      dominance, limits visual performance, and contributes to the pathological
      etiology of amblyopia. Neuregulin-1 (NRG1) signaling through its tyrosine kinase
      receptor ErbB4 is essential for the normal development of the nervous system and
      has been linked to neuropsychiatric disorders such as schizophrenia. We
      discovered recently that NRG1/ErbB4 signaling in PV neurons is critical for the
      initiation of CP visual cortical plasticity by controlling excitatory synaptic
      inputs onto PV neurons and thus PV-cell mediated cortical inhibition that occurs
      following visual deprivation. Building on this discovery, we review the existing
      literature of neuregulin signaling in developing and adult cortex and address the
      implication of NRG/ErbB4 signaling in visual cortical plasticity at the cellular
      and circuit levels. NRG-directed research may lead to therapeutic approaches to
      reactivate plasticity in the adult cortex.

PMID- 29464687
TI  - A Case of Self-Enucleation in an Incarcerated Patient: Case Report and Review of
      Literature.
AB  - Self-enucleation is a severe form of self-injurious behavior which presents as an
      ophthalmologic and psychiatric emergency. It is usually known to occur with
      untreated psychosis, however, there have been reports of self-enucleation across
      various psychopathologies. We review a case documenting self-enucleation in the
      forensic setting in a patient with an unusual presentation and cluster of
      psychotic symptoms. Literature was reviewed using PubMed/Medline databases with
      key terms: "forensic science," "forensic psychiatry," "auto-enucleation," "self
      enucleation," "Oedipism," "self-harm." This case is unique as it offers an
      alternative presentation to those most commonly depicted in current literature,
      helps highlight the sparsity of literature depicting self-enucleation in the
      forensic setting, and stimulates discussion around various potential differential
      diagnoses, management strategies and complications of self-enucleation within the
      forensic setting. It is prudent to emphasize need for aggressive and
      collaborative treatment for the forensic population regardless of
      psychopathology, presentation, or propensity for secondary gain.

PMID- 29464688
TI  - It takes a few to tango: changing climate and fire regimes can cause regeneration
      failure of two subalpine conifers.
AB  - Environmental change is accelerating in the 21st century, but how multiple
      drivers may interact to alter forest resilience remains uncertain. In forests
      affected by large high-severity disturbances, tree regeneration is a resilience
      linchpin that shapes successional trajectories for decades. We modeled stands of
      two widespread western U.S. conifers, Douglas-fir (Pseudotsuga menziesii var.
      glauca), and lodgepole pine (Pinus contorta var. latifolia), in Yellowstone
      National Park (Wyoming, USA) to ask (1) What combinations of distance to seed
      source, fire return interval, and warming-drying conditions cause postfire tree
      regeneration failure? (2) If postfire tree regeneration was successful, how does
      early tree density differ under future climate relative to historical climate? We
      conducted a stand-level (1 ha) factorial simulation experiment using the
      individual-based forest process model iLand to identify combinations of fire
      return interval (11-100 yr), distance to seed source (50-1,000 m), and climate
      (historical, mid-21st century, late-21st century) where trees failed to
      regenerate by 30-yr postfire. If regeneration was successful, we compared stand
      densities between climate periods. Simulated postfire regeneration were
      surprisingly resilient to changing climate and fire drivers. Douglas-fir
      regeneration failed more frequently (55%) than lodgepole pine (28% and 16% for
      non-serotinous and serotinous stands, respectively). Distance to seed source was
      an important driver of regeneration failure for Douglas-fir and non-serotinous
      lodgepole pine; regeneration never failed when stands were 50 m from a seed
      source and nearly always failed when stands were 1 km away. Regeneration of
      serotinous lodgepole pine only failed when fire return intervals were <=20 yr and
      stands were far (1 km) from a seed source. Warming climate increased regeneration
      success for Douglas-fir but did not affect lodgepole pine. If regeneration was
      successful, postfire density varied with climate. Douglas-fir and serotinous
      lodgepole pine regeneration density both increased under 21st-century climate but
      in response to different climate variables (growing season length vs. cold
      limitation). Results suggest that, given a warmer future with larger and more
      frequent fires, a greater number of stands that fail to regenerate after fires
      combined with increasing density in stands where regeneration is successful could
      produce a more coarse-grained forest landscape.

PMID- 29464689
TI  - Distinction of Fly Artifacts from Human Blood using Immunodetection.
AB  - Insect stains produced by necrophagous flies are indistinguishable
      morphologically from human bloodstains. At present, no diagnostic tests exist to
      overcome this deficiency. As the first step toward developing a chemical test to
      recognize fly artifacts, polyclonal antisera were generated in rats against three
      distinct antigenic sequences of fly cathepsin D-like proteinase, an enzyme that
      is structurally distinct in cyclorrhaphous Diptera from other animals. The
      resulting rat antisera bound to artifacts produced by Protophormia terraenovae
      and synthetic peptides used to generate the polyclonal antisera, but not with any
      type of mammalian blood tested in immunoassays. Among the three antisera, anti
      md3 serum displayed the highest reactivity for fly stains, demonstrated cross
      reactivity for all synthetic peptides representing antigenic sequences of the
      mature fly enzyme, and bound artifacts originating from the fly digestive tract.
      Further work is needed to determine whether the antisera are suitable for non
      laboratory conditions.

PMID- 29464690
TI  - BIS monitoring versus clinical assessment for sedation in mechanically ventilated
      adults in the intensive care unit and its impact on clinical outcomes and
      resource utilization.
AB  - BACKGROUND: Patients admitted to intensive care and on mechanical ventilation,
      are administered sedative and analgesic drugs to improve both their comfort and
      interaction with the ventilator. Optimizing sedation practice may reduce
      mortality, improve patient comfort and reduce cost. Current practice is to use
      scales or scores to assess depth of sedation based on clinical criteria such as
      consciousness, understanding and response to commands. However these are
      perceived as subjective assessment tools. Bispectral index (BIS) monitors, which
      are based on the processing of electroencephalographic signals, may overcome the
      restraints of the sedation scales and provide a more reliable and consistent
      guidance for the titration of sedation depth.The benefits of BIS monitoring of
      patients under general anaesthesia for surgical procedures have already been
      confirmed by another Cochrane review. By undertaking a well-conducted systematic
      review our aim was to find out if BIS monitoring improves outcomes in
      mechanically ventilated adult intensive care unit (ICU) patients. OBJECTIVES: To
      assess the effects of BIS monitoring compared with clinical sedation assessment
      on ICU length of stay (LOS), duration of mechanical ventilation, any cause
      mortality, risk of ventilator-associated pneumonia (VAP), risk of adverse events
      (e.g. self-extubation, unplanned disconnection of indwelling catheters), hospital
      LOS, amount of sedative agents used, cost, longer-term functional outcomes and
      quality of life as reported by authors for mechanically ventilated adults in the
      ICU. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, ProQuest,
      OpenGrey and SciSearch up to May 2017 and checked references citation searching
      and contacted study authors to identify additional studies. We searched trial
      registries, which included clinicaltrials.gov and controlled-trials.com.
      SELECTION CRITERIA: We included all randomized controlled trials comparing BIS
      versus clinical assessment (CA) for the management of sedation in mechanically
      ventilated critically ill adults. DATA COLLECTION AND ANALYSIS: We used
      Cochrane's standard methodological procedures. We undertook analysis using Revman
      5.3 software. MAIN RESULTS: We identified 4245 possible studies from the initial
      search. Of those studies, four studies (256 participants) met the inclusion
      criteria. One more study is awaiting classification. Studies were, conducted in
      single-centre surgical and mixed medical-surgical ICUs. BIS monitor was used to
      assess the level of sedation in the intervention arm in all the studies. In the
      control arm, the sedation assessment tools for CA included the Sedation-Agitation
      Scale (SAS), Ramsay Sedation Scale (RSS) or subjective CA utilizing traditional
      clinical signs (heart rate, blood pressure, conscious level and pupillary size).
      Only one study was classified as low risk of bias, the other three studies were
      classified as high risk.There was no evidence of a difference in one study (N =
      50) that measured ICU LOS (Median (Interquartile Range IQR) 8 (4 to 14) in the CA
      group; 12 (6 to 18) in the BIS group; low-quality evidence).There was little or
      no effect on the duration of mechanical ventilation (MD -0.02 days (95% CI -0.13
      to 0.09; 2 studies; N = 155; I2 = 0%; low-quality evidence)). Adverse events were
      reported in one study (N = 105) and the effects on restlessness after suction,
      endotracheal tube resistance, pain tolerance during sedation or delirium after
      extubation were uncertain due to very low-quality evidence. Clinically relevant
      adverse events such as self-extubation were not reported in any study. Three
      studies reported the amount of sedative agents used. We could not measure
      combined difference in the amount of sedative agents used because of different
      sedation protocols and sedative agents used in the studies. GRADE quality of
      evidence was very low. No study reported other secondary outcomes of interest for
      the review. AUTHORS' CONCLUSIONS: We found insufficient evidence about the
      effects of BIS monitoring for sedation in critically ill mechanically ventilated
      adults on clinical outcomes or resource utilization. The findings are uncertain
      due to the low- and very low-quality evidence derived from a limited number of
      studies.

PMID- 29464691
TI  - A pilot study of hyperoxemia on neurological injury, inflammation and oxidative
      stress.
AB  - BACKGROUND: Normobaric hyperoxia is used to alleviate secondary brain ischaemia
      in patients with traumatic brain injury (TBI), but clinical evidence is limited
      and hyperoxia may cause adverse events. METHODS: An open label, randomised
      controlled pilot study comparing blood concentrations of reactive oxygen species
      (ROS), interleukin 6 (IL-6) and neuron-specific enolase (NSE) between two
      different fractions of inspired oxygen in severe TBI patients on mechanical
      ventilation. RESULTS: We enrolled 27 patients in the Fi O2 0.40 group and 38 in
      the Fi O2 0.70 group; 19 and 23 patients, respectively, completed biochemical
      analyses. In baseline, there were no differences between Fi O2 0.40 and Fi O2
      0.70 groups, respectively, in ROS (64.8 nM [22.6-102.1] vs. 64.9 nM [26.8-96.3],
      P = 0.80), IL-6 (group 92.4 pg/ml [52.9-171.6] vs. 94.3 pg/ml [54.8-133.1], P =
      0.52) or NSE (21.04 ug/l [14.0-30.7] vs. 17.8 ug/l [14.1-23.9], P = 0.35). ROS
      levels did not differ at Day 1 (24.2 nM [20.6-33.5] vs. 29.2 nM [22.7-69.2], P =
      0.10) or at Day 2 (25.4 nM [21.7-37.4] vs. 47.3 nM [34.4-126.1], P = 0.95). IL-6
      concentrations did not differ at Day 1 (112.7 pg/ml [65.9-168.9) vs. 83.9 pg/ml
      [51.8-144.3], P = 0.41) or at Day 3 (55.0 pg/ml [34.2-115.6] vs. 49.3 pg/ml [34.4
      126.1], P = 0.95). NSE levels did not differ at Day 1 (15.9 ug/l [9.0-24.3] vs.
      15.3 ug/l [12.2-26.3], P = 0.62). There were no differences between groups in the
      incidence of pulmonary complications. CONCLUSION: Higher fraction of inspired
      oxygen did not increase blood concentrations of markers of oxidative stress,
      inflammation or neurological injury or the incidence of pulmonary complications
      in severe TBI patients on mechanical ventilation.

PMID- 29464692
TI  - Misconceptions and Realities of the Prescription Opioid Epidemic.
AB  - The abuse of opioids in the US is not a new problem. In 1973 David Musto
      published his book, The American Disease: Origins of Narcotic Control, which
      described the problem as dating back to the time of the Civil War. Continued
      attempts to address it through legislation, law enforcement, prevention,
      treatment, and the development of less abuseable pain relievers have shown
      limited success.

PMID- 29464693
TI  - The Role of Postmortem Computed Tomography in the Evaluation of Strangulation
      Deaths.
AB  - We explored the value of postmortem computed tomography (PMCT) to augment autopsy
      in evaluating strangulation fatalities. A literature search identified 16 studies
      describing autopsy findings in 576 deaths and two studies describing autopsy and
      PMCT findings in six deaths. Similar cases were identified from our institution,
      yielding 130 deaths with autopsy findings and 14 deaths with both autopsy and
      PMCT findings. The presence of laryngohyoid fracture and soft tissue hemorrhage
      was compared from autopsy and autopsy+PMCT cases. The detection rates of
      fractures in autopsy and autopsy+PMCT cases were not significantly different.
      PMCT identified all fractures observed at autopsy and five fractures not
      identified. While PMCT may not detect soft tissue injuries in decomposed remains
      or subtle internal hemorrhages in neck injury, it is equally able to detect bony
      injuries as autopsy and might surpass autopsy in detecting subtle fractures. We
      conclude PMCT is useful to supplement autopsy in strangulation cases.

PMID- 29464694
TI  - The evolution of floral signals in relation to range overlap in a clade of
      California Jewelflowers (Streptanthus s.l.).
AB  - Because of their function as reproductive signals in plants, floral traits
      experience distinct selective pressures related to their role in speciation,
      reinforcement, and prolonged coexistence with close relatives. However, few
      studies have investigated whether population-level processes translate into
      detectable signatures at the macroevolutionary scale. Here, we ask whether
      patterns of floral trait evolution and range overlap across a clade of California
      Jewelflowers reflect processes hypothesized to shape floral signal
      differentiation at the population level. We found a pattern of divergence in
      floral scent composition across the clade such that close relatives had highly
      disparate floral scents given their age. Accounting for range overlap with close
      relatives explained additional variation in floral scent over time, with
      sympatric species pairs having diverged more than allopatric species pairs given
      their age. However, three other floral traits (flower size, scent complexity and
      flower color) did not fit these patterns, failing to deviate from a null Brownian
      motion model of evolution. Together, our results suggest that selection for
      divergence among close relatives in the composition of floral scents may play a
      key, sustained role in mediating speciation and coexistence dynamics across this
      group, and that signatures of these dynamics may persist at the macroevolutionary
      scale.

PMID- 29464695
TI  - Time Radically Alters Ex Situ Evidentiary Soil 16S Bacterial Profiles Produced
      Via Next-Generation Sequencing,.
AB  - Previous research has revealed the potential of soil bacterial profiling for
      forensic purposes; however, investigators have not thoroughly examined
      fluctuations in microbial profiles from soil aged on evidence. In this research,
      soils collected from multiple habitats were placed on evidence items and sampled
      over time, and then bacterial profiles were generated via next-generation
      sequencing of the 16S rRNA locus. Bacterial abundance charts and nonmetric
      multidimensional scaling plots provided visual representation of bacterial
      profiles temporally, while supervised classification was used to statistically
      associate evidence to a source. The ex situ evidence soils displayed specific,
      consistent taxonomic changes as they aged, resulting in their drift in
      multidimensional space, but never toward a different habitat. Ninety-five percent
      of the 364 evidentiary profiles statistically classified to the correct habitat,
      with misclassification generally stemming from evidence type and increased age.
      Ultimately, understanding bacterial changes that occur temporally in ex situ
      soils should enhance their use in forensic investigations.

PMID- 29464698
TI  - Dual-guild herbivory disrupts predator-prey interactions in the field.
AB  - Plant defenses often mediate whether competing chewing and sucking herbivores
      indirectly benefit or harm one another. Dual-guild herbivory also can muddle
      plant signals used by specialist natural enemies to locate prey, further
      complicating the net impact of herbivore-herbivore interactions in naturally
      diverse settings. While dual-guild herbivore communities are common in nature,
      consequences for top-down processes are unclear, as chemically mediated tri
      trophic interactions are rarely evaluated in field environments. Combining
      observational and experimental approaches in the open field, we test a prediction
      that chewing herbivores interfere with top-down suppression of phloem feeders on
      Brassica oleracea across broad landscapes. In a two-year survey of 52 working
      farm sites, we found that parasitoid and aphid densities on broccoli plants
      positively correlated at farms where aphids and caterpillars rarely co-occurred,
      but this relationship disappeared at farms where caterpillars commonly co
      occurred. In a follow-up experiment, we compared single and dual-guild herbivore
      communities at four local farm sites and found that caterpillars (P. rapae)
      caused a 30% reduction in aphid parasitism (primarily by Diaeretiella rapae), and
      increased aphid colony (Brevicoryne brassicae) growth at some sites. Notably, in
      the absence of predators, caterpillars indirectly suppressed, rather than
      enhanced, aphid growth. Amid considerable ecological noise, our study reveals a
      pattern of apparent commensalism: herbivore-herbivore facilitation via relaxed
      top-down suppression. This work suggests that enemy-mediated apparent
      commensalism may override constraints to growth induced by competing herbivores
      in field environments, and emphasizes the value of placing chemically mediated
      interactions within their broader environmental and community contexts.

PMID- 29464699
TI  - Immune checkpoint blockade combined with IL-6 and TGF-beta inhibition improves
      the therapeutic outcome of mRNA-based immunotherapy.
AB  - Improved understanding of cancer immunology has provided insight into the
      phenomenon of frequent tumor recurrence after initially successful immunotherapy.
      A delicate balance exists between the capacity of the immune system to control
      tumor growth and various resistance mechanisms that arise to avoid or even
      counteract the host's immune system. These resistance mechanisms include but are
      not limited to (i) adaptive expression of inhibitory checkpoint molecules in
      response to the proinflammatory environment and (ii) amplification of cancer stem
      cells, a small fraction of tumor cells possessing the capacity for self-renewal
      and mediating treatment resistance and formation of metastases after long periods
      of clinical remission. Several individual therapeutic agents have so far been
      developed to revert T-cell exhaustion or disrupt the cross-talk between cancer
      stem cells and the tumor-promoting microenvironment. Here, we demonstrate that a
      three-arm combination therapy-consisting of an mRNA-based vaccine to induce
      antigen-specific T-cell responses, monoclonal antibodies blocking inhibitory
      checkpoint molecules (PD-1, TIM-3, LAG-3), and antibodies targeting IL-6 and TGF
      beta-improves the therapeutic outcome in subcutaneous TC-1 tumors and
      significantly prolongs survival of treated mice. Our findings point to a need for
      a rational development of multidimensional anticancer therapies, aiming at the
      induction of tumor-specific immunity and simultaneously targeting multiple
      resistance mechanisms.

PMID- 29464700
TI  - Septic Cavernous Sinus Thrombosis Following a Minor Head Injury: A Rare Cause of
      Medico-Legal Death.
AB  - Septic cavernous sinus thrombosis (SCST) is an uncommon consequence of head and
      face infection, but a rare complication after craniofacial fracture. In this
      case, SCST developed in a 13-year-old girl following a minor fall during
      volleyball, with impact and resulting abrasive contusion of the left forehead.
      She developed watery rhinorrhea, progressive headache, fever, nausea, vomiting,
      and left proptosis with blurred vision, and was admitted to hospital 3 days after
      injury. Drowsiness, high-grade fever, severe headache, left ocular pain with
      marked periorbital swelling, and paralysis of extraocular eye movements
      developed. Computed tomography scan identified left sphenoid and ethmoid
      sinusitis, a posterior clinoid fracture, and septic cavernous sinus thrombosis.
      She died after 10 days of in-hospital antibiotic therapy. Death was due to
      Staphylococcus aureus sepsis with septic pulmonary thromboemboli due to
      suppurative meningitis and cerebral infarction, due to SCST following apparently
      minor blunt head injury from an accidental fall.

PMID- 29464701
TI  - Analysis of Class Characteristics of Reciprocating Saws.
AB  - Criminal dismemberment is accomplished using a variety of tools and frequently
      used to dispose or facilitate the transport of human remains in an attempt to
      hinder forensic investigation. The present research examined features that may
      differentiate cuts made in bone by various commercially available reciprocating
      saw blades. The partial limbs of adult white-tailed deer (Odocoileus virginianus)
      were used as a proxy for human remains and were cut using five reciprocating saw
      blades and a hand-powered hacksaw. The resulting false start and complete kerfs
      were examined macroscopically and microscopically. Kerf characteristics in which
      significant differences (p <= 0.05) between reciprocating blades were noted
      including minimum kerf width, kerf false start shape, presence of cut surface
      drift and harmonics, exit chipping size, and striation regularity. Interblade
      differences generally reflect class characteristics previously established for
      hand-powered blades. The present research may aid in the identification of
      reciprocating saw use in forensic contexts.

PMID- 29464702
TI  - Identifying Differences Between Cut Marks Made on Bone by a Machete and Katana: A
      Pilot Study.
AB  - The aim of this research was to identify characteristics specific to a machete
      and katana on three different bone types. One machete and two katanas were used
      to produce cut marks on Sus scrofa rib, flat and long bones. Fifty-nine cuts were
      produced by the katanas and 38 by the machete. The presence of flaking,
      feathering, peeling, micropeeling, chattering, microcurvature, scoop defect, and
      exit notch was noted, and bivariate associations between each characteristic and
      weapon type were assessed using Pearson's chi-square tests for independence and
      logistic regression models developed. Significant predictors for machete cut
      marks are scoop defect for rib bones (correct classification 93%), micropeeling
      in flat bones, chattering on flat and long bones (all p < 001) and for the
      katana, microcurvature (p < 004) and exit notch on flat and long bones (p < 001;
      correct classification 96% and 100%, respectively). The identified bivariate
      associations and final logistic regression models may be utilized in forensic
      investigations when identifying hacking trauma.

PMID- 29464703
TI  - A Comparison Among Three Multiplex Y-STR Profiling Kits for Sexual Assault Cases.
AB  - Biological evidence of sexual assault is one of the most difficult sample types
      to analyze in forensic laboratories. Y-STR markers are thus a valuable tool for
      analyzing these samples. The aim of this project was to compare three Y-STR
      commercial kits by analyzing their amplification performance on casework samples.
      Overall, 247 trace samples were analyzed with a Yfiler(r) Plus PCR Amplification
      Kit (Applied Biosystems), PowerPlex(r) Y23 (Promega(r) ) System and AmpFLSTR(r)
      YfilerTM PCR Amplification Kit (Applied Biosystems). Comparing the amplification
      performance of the three kits, the first two were significantly more sensitive
      than the latter (p < 0.001). For samples, with a male DNA quantity less than 0.5
      ng, the PowerPlex Y23(r) kit was the most sensitive and best performing kit,
      followed by the Yfiler(r) Plus kit (p = 0.009). In conclusion, the Yfiler(r) Plus
      and PowerPlex Y-23(r) kits are viable alternatives to older kits for samples with
      low amounts of male DNA.

PMID- 29464704
TI  - Epilepsy with auditory features: Long-term outcome and predictors of terminal
      remission.
AB  - OBJECTIVE: To assess the long-term outcome of epilepsy with auditory features
      (EAF) and to identify the clinical predictors for prognosis. METHODS: The study
      involved consecutive EAF patients with a follow-up of >=5 years. Terminal
      remission (TR) was defined as a period of >=5 consecutive years of seizure
      freedom at the last follow-up. We used Kaplan-Meier estimate to calculate the
      cumulative time-dependent probability of conversion to TR. Log-rank test and
      multivariate Cox regression analyses were performed to study the association
      between time to TR and prognostic determinants. RESULTS: We included 123 EAF
      patients (male/female = 58/65) with a median follow-up of 11 years (1626.9 person
      years). Most were sporadic cases (68.3%), whereas 31.7% reported a family history
      of epilepsy. At last assessment, 42 patients had achieved TR (34.1%). Of the
      remaining 81 cases with no TR (65.9%), 37% had been in remission for 1-4 years
      and 62.9% still had seizures within the past year. The cumulative rates of TR
      were 26.6%, 35.7%, and 51.6% at 10, 20, and 30 years from inclusion. On
      multivariate analysis, age at onset > 10 years (hazard ratio [HR] = 3.2, P =
      .028), auditory aura characterized by distortions only versus simple/complex
      hallucinations (HR = 2.9, P = .041), and unremarkable scalp electroencephalogram
      (EEG) versus EEG with focal epileptiform activity (HR = 3.5, P = .041) were
      associated with TR. SIGNIFICANCE: Our data show a wide prognostic spectrum of
      EAF, ranging from mild forms with spontaneous remission, to severely refractory
      epilepsy addressed to surgery. The outcome, less favorable than expected from
      previous studies, appears to be primarily a function of 3 prognostic negative
      risk factors: age at onset < 10 years, auditory aura characterized by complex
      auditory hallucinations, and focal epileptiform abnormalities on scalp EEG. These
      predictors, easy to collect even at the first visit, may inform both clinicians
      and patients about the long-term prognosis and aid patient management.

PMID- 29464705
TI  - Variations in Australian dental therapy practice by practitioner and workplace
      characteristics.
AB  - INTRODUCTION: Understanding dental therapy practice across clinical settings is
      useful for education and service planning. This study assessed if dental therapy
      service provision varied according to practitioner and workplace characteristics.
      METHODS: Members of professional associations representing dental therapists (DT)
      and oral health therapists (OHT) were posted a self-complete survey collecting
      practitioner and workplace characteristics, together with clinical activity on a
      self-selected typical day of practice. Differences in service provision according
      to characteristics were assessed by comparing mean services per patient visit.
      Negative binomial regression models estimated adjusted ratios (R) of mean
      services per patient. RESULTS: The response rate was 60.6%. Of practitioners
      registered as an OHT or a DT, 80.0% (n = 500) were employed in general clinical
      practice. Nearly one-third of OHT and nearly two-thirds of DT worked in public
      sector dental services. Patterns of service provision varied significantly
      according to practice sector and other characteristics. After adjusting for
      characteristics, relative to private sector, public sector practitioners had
      higher provision rates of fissure sealants (R = 3.79, 95% confidence interval
      [95% CI]: 2.84-5.06), restorations (R = 3.78, 95% CI: 2.94-4.86) and deciduous
      tooth extractions (R = 3.58, 95% CI: 2.60-4.93) per patient visit, and lower
      provision rates of oral health instruction (R = 0.86, 95% CI: 0.76-0.98),
      fluoride applications (R = 0.43, 95% CI: 0.33-0.56), scale and cleans (R = 0.39,
      95% CI: 0.34-0.45) and periodontal services (R = 0.20, 95% CI: 0.14-0.28) per
      patient visit. CONCLUSION: Differences in service provision according to sector
      indicate that OHT and DT adapt to differing patient groups and models of care.
      Variations may also indicate that barriers to utilising the full scope of
      practice exist in some settings.

PMID- 29464706
TI  - A Systems Approach to Biometrics in the Military Domain.
AB  - Forensic biometrics is the application of forensic science principles to physical
      and behavioral characteristics. Forensic biometrics is a secondary sub-system in
      the forensic science "system of systems," which describes forensic science as a
      sub-system in the larger criminal justice, law enforcement, intelligence, and
      military system. The purpose of this paper is to discuss biometrics in the
      military domain and integration into the wider forensic science system of
      systems. The holistic system thinking methodology was applied to the U.S.
      biometric system to map it to the system of systems framework. The U.S. biometric
      system is used as a case study to help guide other countries to develop military
      biometric systems that are integrated and interoperable at the whole-of
      government level. The aim is to provide the system of systems framework for
      agencies to consider for proactive design of biometric systems.

PMID- 29464707
TI  - From paediatrics to geriatrics: ageing with a neurodevelopmental disability.

PMID- 29464708
TI  - Empowerment and partnership: stronger together.

PMID- 29464709
TI  - Corrigendum.

PMID- 29464710
TI  - What is in a name? A closer look at callosotomies.

PMID- 29464711
TI  - Precious young adults born late-preterm: how much follow-up is enough?

PMID- 29464712
TI  - Corrigendum.

PMID- 29464714
TI  - Development of heart failure in patients with rheumatoid arthritis: A Danish
      population-based study.
AB  - BACKGROUND: To investigate the incidence of heart failure (HF) and ischaemic
      heart disease (IHD) in different time spans following incident rheumatoid
      arthritis (RA) and, furthermore, to investigate the impact of IHD on the
      development of HF and the impact of different treatment era of RA. MATERIALS AND
      METHODS: This matched cohort study used nationwide, prospectively collected data.
      From the total Danish population of approximately 5.7 million inhabitants, we
      identified 51 859 patients (between 1995 and July 2016) with incident RA and a
      sex- and age-matched cohort from the general population (256 653 persons).
      RESULTS: The hazard ratio (HR) for HF among RA patients compared with persons
      from comparison cohort was 2.28 within the first year of index date, 1.39 within
      the 1-5 years of index date and 1.38 within the 5-10 years of index date. No
      difference was identified regarding different treatment era of RA. For IHD, the
      subdistribution hazard ratio (sHR) was 1.93 within the first year of index date,
      1.26 within the 1-5 years of index date and 1.31 within the 5-10 years of index
      date. Coronary revascularization was also more common within the first year after
      diagnosis of RA. An increased risk of percutaneous coronary intervention and
      coronary artery bypass grafting within 10 years following the RA diagnosis was
      observed. HR for new onset of HF in RA without IHD was 1.23, while the HR for new
      onset of HF in patients with RA and IHD was 2.06. CONCLUSIONS: Rheumatoid
      arthritis patients had higher rates of HF and IHD throughout the entire
      observation period compared to the comparison cohort. RA was associated with a
      larger risk of developing HF.

PMID- 29464713
TI  - The psychosocial burden of hand eczema: Data from a European dermatological
      multicentre study.
AB  - BACKGROUND: The essential physical role, visibility and social importance of the
      hands place a major psychological burden on patients with hand eczema.
      OBJECTIVES: The aim of this study was to identify the psychological, social and
      clinical characteristics of patients with hand eczema, in particular the
      prevalences of depression, anxiety, suicidal ideation, and comorbidities.
      MATERIALS AND METHODS: Data on patients with hand eczema were analysed from a
      large European multicentre study conducted with dermatology outpatients from 13
      countries. Groups of patients and controls were compared to analyse the
      psychological burden of hand eczema. RESULTS: Female patients with hand eczema
      had higher Hospital Anxiety and Depression Scale (HADS) scores for anxiety (n =
      86, median = 7.0) than controls (n = 900, median = 5.0, P = .02), and for
      depression (median = 4.0) than controls (3.0, P < .001). Patients with high
      suicidal ideation, with low socioeconomic status and who were widowed or divorced
      were more likely to fulfil the HADS criteria for anxiety [odds ratio (OR) > 1, P
      = .038, P < .001, and P < .001, respectively]. The median Dermatology Life
      Quality Index score was 7.0 (n = 68). DISCUSSION: This study identifies a
      specific psychological burden experienced by hand eczema patients, highlighting
      the need for focused psychosocial interventions. Physicians in particular should
      be aware of the need to identify anxiety and depression in female patients.

PMID- 29464715
TI  - Occupational allergic contact dermatitis caused by hexahydrophthalic acid
      diglycidyl ester and anhydride epoxy hardeners.

PMID- 29464716
TI  - Richter transformation driven by Epstein-Barr virus reactivation during therapy
      related immunosuppression in chronic lymphocytic leukaemia.
AB  - The increased risk of Richter transformation (RT) in patients with chronic
      lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during
      immunosuppressive therapy with fludarabine other targeted agents remains
      controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma
      (DLBCL), seven (23%) showed EBV expression. In contrast to EBV- tumours, EBV+
      DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed CLL
      unrelated IGVH sequences more frequently. Intriguingly, despite having different
      cellular origins, clonally related and unrelated EBV+ DLBCLs shared a previous
      history of immunosuppressive chemo-immunotherapy, a non-germinal centre DLBCL
      phenotype, EBV latency programme type II or III, and very short survival. These
      data suggested that EBV reactivation during therapy-related immunosuppression can
      transform either CLL cells or non-tumoural B lymphocytes into EBV+ DLBCL. To
      investigate this hypothesis, xenogeneic transplantation of blood cells from 31
      patients with CLL and monoclonal B-cell lymphocytosis (MBL) was performed in Rag2
      /- IL2gammac-/- mice. Remarkably, the recipients' impaired immunosurveillance
      favoured the spontaneous outgrowth of EBV+ B-cell clones from 95% of CLL and 64%
      of MBL patients samples, but not from healthy donors. Eventually, these cells
      generated monoclonal tumours (mostly CLL-unrelated but also CLL-related),
      recapitulating the principal features of EBV+ DLBCL in patients. Accordingly,
      clonally related and unrelated EBV+ DLBCL xenografts showed indistinguishable
      cellular, virological and molecular features, and synergistically responded to
      combined inhibition of EBV replication with ganciclovir and B-cell receptor
      signalling with ibrutinib in vivo. Our study underscores the risk of RT driven by
      EBV in CLL patients receiving immunosuppressive therapies, and provides the
      scientific rationale for testing ganciclovir and ibrutinib in EBV+ DLBCL.
      Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 29464717
TI  - Allergic contact dermatitis caused by sodium cetearyl sulfate.

PMID- 29464718
TI  - Technical Note: Feasibility of MRI-based estimation of water-equivalent path
      length to detect changes in proton range during treatment courses.
AB  - PURPOSE: To evaluate the feasibility of using on-treatment magnetic resonance
      imaging (MRI) to detect proton range changes during treatment courses. METHODS:
      MRI-based virtual computed tomography (vCT) was generated to calculate water
      equivalent path length (WEPL) at the distal surface of a clinical target volume.
      T2-weighted MR images with and without fat suppression were processed by
      thresholding and fuzzy c-mean clustering to assign a bulk HU (Hounsfield Unit) to
      each segment of fat, water, and air. Bony tissues in vCT were transferred from
      planning CT via a region-based registration. We validated this method using
      images from three patients (aged 9, 12, and 17 yr old) with pelvic sarcomas who
      underwent proton therapy. MRI-based WEPL was evaluated against those of repeat CT
      (rCT) and cone beam CT (CBCT). RESULTS: The vCT agreed well with the rCT, wherein
      the use of bulk HU and imperfect bone registration contributed to discrepancies.
      The 99th percentile error of the MRI-based WEPL was up to 3.3 mm for posterior
      fields when we compensated the effect of mobile air. The gamma index (2-mm WEPL/2
      mm pixel distance) was greater than 99% for those fields. We observed larger
      errors for anterior fields, which were due to bowel gas movement, mismatched
      respiratory motion, and differences in patient posture between the vCT and rCT.
      Applied to multiple on-treatment MRI of a patient, the estimated WEPL
      demonstrated an underrange trend, which was consistent with the CBCT results and
      the increased patient body circumference. CONCLUSIONS: The MRI-based vCT produced
      highly accurate WEPL estimates, demonstrating the potential of using on-treatment
      MRI for detecting changes in proton ranges.

PMID- 29464719
TI  - Blood donation history and eligibility assessment in a community-based sample of
      men who have sex with men.
AB  - BACKGROUND: In 2016, the US Food and Drug Administration changed the regulation
      from a permanent deferral from donation for men who have sex with men (MSM) to a
      1-year deferral since last sexual contact. It is unknown what proportions of MSM
      try to donate and if they would be willing to answer individual risk-based
      questions to assess their current eligibility. STUDY DESIGN AND METHODS: The
      National HIV Behavioral Surveillance surveys periodically measure human
      immunodeficiency virus (HIV) prevalence and risk behaviors among MSM using a
      venue-based, time-location sampling method. In the 2014 cycle, that is, before
      the policy change, investigators in San Francisco and New Orleans added questions
      about blood donation. Questions inquired into three domains: donation history,
      policy awareness, and knowledge about HIV testing of donations. RESULTS: There
      were 404 and 557 respondents in San Francisco and New Orleans, respectively.
      Nearly one in three MSM in San Francisco (27.4%) and New Orleans (31.4%) tried to
      donate after their first MSM contact. A majority (63.1% in San Francisco, 58.8%
      in New Orleans) somewhat or strongly agreed that they would be willing to be
      asked detailed questions for donation eligibility assessment. CONCLUSIONS: The
      proportion of MSM who reported trying to donate was similar in the two cities.
      However, a substantial proportion did not agree to be asked more detailed risk
      behavior questions to assess eligibility. In these two geographic locations,
      prominent regional differences were not evident.

PMID- 29464720
TI  - The re-emergence of hallucinogenic research.
AB  - Due to the intractability, at times, in the treatment of PTSD, clinicians and
      researchers continue to explore different options for treatment. This article
      discusses the renewed interest in hallucinogens for such treatment.

PMID- 29464721
TI  - Physiological response of 10 phytoplankton species exposed to macondo oil and the
      dispersant, Corexit.
AB  - Culture experiments were conducted on ten phytoplankton species to examine their
      biological and physiological responses during exposure to oil and a combination
      of oil and dispersant. The species tested included a range of taxa typically
      found in the Gulf of Mexico such as cyanobacteria, chlorophytes, and diatoms.
      Cultures were exposed to Macondo surrogate oil using the water accommodated
      fraction (WAF), and dispersed oil using a chemically enhanced WAF (CEWAF) and
      diluted CEWAF, to replicate conditions following the Deepwater Horizon spill in
      the Gulf of Mexico. A range of responses were observed, that could broadly class
      the algae as either "robust" or "sensitive" to oil and/or dispersant exposure.
      Robust algae were identified as Synechococcus elongatus, Dunaliella tertiolecta,
      two pennate diatoms Phaeodactylum tricornutum and Navicula sp., and Skeletonema
      grethae CCMP775, and were largely unaffected by any of the treatments (no changes
      to growth rate or time spent in lag phase relative to controls). The rest of the
      phytoplankton, all centric diatoms, exhibited at least some combination of
      reduced growth rates or increased lag time in response to oil and/or dispersant
      exposure. Photophysiology did not have a strong treatment effect, with
      significant inhibition of photosynthetic efficiency (Fv /Fm ) only observed in
      the CEWAF, if at all. We found that the effects of oil and dispersants on
      phytoplankton physiology were species-dependent, and not always detrimental. This
      has significant implications on how oil spills might impact phytoplankton
      community structure and bloom dynamics in the Gulf of Mexico, which in turn
      impacts higher trophic levels.

PMID- 29464722
TI  - Phelipanche aegyptiaca parasitism impairs salinity tolerance in young leaves of
      tomato.
AB  - The parasite Phelipanche aegyptiaca infests tomato, a crop plant that is commonly
      cultivated in semi-arid environments, where tomato may be subject to salt stress.
      Since the relationship between the two stresses -salinity and parasitism - has
      been poorly investigated in tomato, the effects of P. aegyptiaca parasitism on
      tomato growing under moderate salinity were examined. Tomatoes were grown with
      regular or saline water irrigation (3 and 45 mM Cl- , respectively) in soils
      infested with P. aegyptiaca. The infested plants accumulated higher levels of
      sodium and chloride ions in the roots, shoots and leaves (old and young) under
      both salinity levels vs. non-infected plants. There was a positive linear
      correlation between P. aegyptiaca biomass and salt accumulation in young tomato
      leaves, and a negative linear correlation between parasite biomass and the
      osmotic potential of young tomato leaves. Concentrations of the osmoprotectants
      proline, myoinositol and sucrose were reduced in infected tomato plants, which
      impaired the host's osmotic adjustment ability. The sensitivity of P. aegyptiaca
      to salt stress was manifested as a decrease in biomass. In conclusion, P.
      aegyptiaca parasitism reduced the salt tolerance of tomato plants by promoting
      the accumulation of salts from the rhizosphere and impairing the host's osmotic
      adjustment ability.

PMID- 29464723
TI  - A unique major histocompatibility complex Class II-binding register correlates
      with HLA-DR11-associated immunogenicity of the major K blood group antigen.
AB  - BACKGROUND: Kell is a glycoprotein expressed on red blood cells (RBCs). Its K and
      k variants contain either Met (K antigen) or Thr (k antigen) at Position 193,
      respectively. Development of anti-K after K-mismatched antigen exposure via blood
      transfusions or pregnancy can destroy RBCs, leading to hemolytic transfusion
      reactions and hemolytic disease of the fetus and newborn. The immunogenicity of
      overlapping 15-mer Kell peptides with M193 or T193 at every possible position was
      investigated previously. Interestingly, Peptide W179 to M193, with the
      polymorphic M193T residue at the peptide's C-terminus, was the most effective at
      stimulating CD4 T cells from a series of K-immunized women. STUDY DESIGN AND
      METHODS: This study investigates the basis for HLA restriction of anti-K immune
      responses. Major histocompatibility complex Class II (MHCII)-binding prediction
      algorithms and quantitative peptide-MHCII-binding assays were employed to
      determine the binding registers; anchor residues; and affinities of wild-type,
      truncated, and sequence-modified K and k peptides. Predictions were generated
      using Immune Epitope Database and ProPred algorithms. Competitive peptide-MHCII
      binding assays utilized 12 recombinant HLA-DR proteins, K and k peptides, and
      high-affinity MHCII-restricted reference peptides. RESULTS: The peptide-MHCII
      binding assays identified a unique K peptide-binding register (W179-S187)
      restricted to HLA-DRB1*11:01, in addition to partially overlapping binding
      registers that included the K/k M193T polymorphic site and that bound
      promiscuously to multiple HLA-DR proteins. CONCLUSION: Three partially
      overlapping MHCII-binding motifs for HLA-DRB1*11:01 result in high-avidity K
      peptide binding, which may contribute to HLA-DR11-restricted immunogenicity
      associated with the K allele.

PMID- 29464724
TI  - Exploring and exploiting the boundaries of host specificity using the cereal rust
      and mildew models.
AB  - Individual plants encounter a vast number of microbes including bacteria,
      viruses, fungi and oomycetes through their growth cycle, yet few of these
      pathogens are able to infect them. Plant species have diverged over millions of
      years, co-evolving with few specific pathogens. The host boundaries of most
      pathogen species can be clearly defined. In general, the greater the genetic
      divergence from the preferred host, the less likely that pathogen would be able
      to infect that plant species. Co-evolution and divergence also occur within
      pathogen species, leading to highly specialized subspecies with narrow host
      ranges. For example, cereal rust and mildew pathogens (Puccinia and Blumeria
      spp.) display high host specificity as a result of ongoing co-evolution with a
      narrow range of grass species. In rare cases, however, some plant species are in
      a transition from host to nonhost or are intermediate hosts (near nonhost).
      Barley was reported as a useful model for genetic and molecular studies of
      nonhost resistance due to rare susceptibility to numerous heterologous rust and
      mildew fungi. This review evaluates host specificity in numerous
      Puccinia/Blumeria-cereal pathosystems and discusses various approaches for
      transferring nonhost resistance (NHR) genes between crop species to reduce the
      impact of important diseases in food production.

PMID- 29464725
TI  - Gibberellin antagonizes jasmonate-induced defense against Meloidogyne graminicola
      in rice.
AB  - Gibberellin (GA) regulates various plant growth and developmental processes, but
      its role in pathogen attack, and especially nematode-plant interactions, still
      remains to be elucidated. An in-depth characterization of the role of GA in
      nematode infection was conducted using mutant lines of rice, chemical inhibitors,
      and phytohormone measurements. Our results showed that GA influences rice
      Meloidogyne graminicola interactions in a concentration-dependent manner. Foliar
      spray of plants with a low concentration of gibberellic acid enhanced nematode
      infection. Biosynthetic and signaling mutants confirmed the importance of
      gibberellin for rice susceptibility to M. graminicola infection. Our study also
      demonstrates that GA signaling suppresses jasmonate (JA)-mediated defense against
      M. graminicola, and likewise the JA-induced defense against M. graminicola
      requires SLENDER RICE1 (SLR1)-mediated repression of the GA pathway. In contrast
      to observations from other plant-pathogen interactions, GA plays a dominant role
      over JA in determining susceptibility to M. graminicola in rice. This GA-induced
      nematode susceptibility was largely independent of auxin biosynthesis, but relied
      on auxin transport. In conclusion, we showed that GA-JA antagonistic crosstalk is
      at the forefront of the interaction between rice and M. graminicola, and SLR1
      plays a central role in the JA-mediated defense response in rice against this
      nematode.

PMID- 29464726
TI  - Changes in D-dimer concentration after soft tissue and orthopedic surgery in
      dogs.
AB  - OBJECTIVE: D-dimer is a specific marker of active coagulation and fibrinolysis.
      The objective of this study is to determine the influence of surgery on D-dimer
      concentration as well as to examine the relation between the magnitude of change
      and invasiveness of the surgical procedures. STUDY DESIGN: Prospective clinical
      study. ANIMALS: Forty-five client-owned dogs undergoing elective neutering (n =
      15), elective orthopedic (n = 15), or posttraumatic orthopedic (n = 15) surgical
      procedures. METHODS: Dogs undergoing elective neutering, elective orthopedic, and
      posttraumatic orthopedic surgical procedures were enrolled. D-dimer
      concentration, measured immediately prior to, immediately after, and 24 hours
      after surgery (T0, T1, and T24, respectively), was compared within and among
      study groups. RESULTS: D-dimer concentration was >250 ng/mL in 8 (18%) dogs at
      T0, in 9 (20%) at T1, and in 5 (11%) at T24. At T1 and T24, only 2 dogs had a D
      dimer concentration >500 ng/mL, and it was <750 ng/mL in all dogs. There was no
      difference in the proportion of increased D-dimer concentration (>250 ng/mL)
      among the time points (P = 0.29). Median D-dimer concentration did not vary
      between time points within the groups, except in the neutering group (P = 0.029),
      in which T1 concentration tended to increase compared with T0 values (161 ng/dL,
      range 71-727 vs 122 ng/mL, range, 43-353, respectively; P = .065). CONCLUSION:
      The surgical procedures tested in this study are unlikely to cause a direct
      increase in D-dimer concentration. CLINICAL SIGNIFICANCE: Any increase in D-dimer
      concentration after elective neutering, elective orthopedic, and posttraumatic
      orthopedic surgical procedures should be regarded as clinically important and
      trigger investigations to detect a hemostatic derangement.

PMID- 29464727
TI  - Class III peroxidases in cellulose deficient cultured maize cells during cell
      wall remodeling.
AB  - Maize (Zea mays L.) suspension-cultured cells habituated to a cellulose
      biosynthesis inhibitor 2,6-dichlorobenzonitrile (DCB) have a modified cell wall,
      in which the reduction in the cellulose content is compensated by a network of
      highly cross-linked feruloylated arabinoxylans and the deposition of lignin-like
      polymers. For both arabinoxylan cross-linking and lignin polymerization, class
      III peroxidases (POXs) have been demonstrated to have a prominent role. For the
      first time, a comparative study of POX activity and isoforms in control and
      cellulose-impaired cells has been addressed, also taking into account their
      cellular distribution in different compartments. Proteins from the spent medium
      (SM), soluble cellular (SC), ionically (ICW) and covalently bound cell wall
      protein fractions were assayed for total and specific peroxidase activity by
      using coniferyl and sinapyl alcohol and ferulic acid as substrates. The isoPOX
      profile was obtained by isoelectric focusing. POX activity was higher in DCB
      habituated than in non-habituated cells in all protein fractions at all cell
      culture stages. For all substrates assayed, SC and ICW fractions showed higher
      activity at the early log growth phase than at the late log phase. However, the
      highest POX activity in the spent medium was found at the late log phase.
      According to the isoPOX profiles, the highest diversity of isoPOXs was detected
      in the ICW and SM protein fractions. The latter fraction contained isoPOXs with
      higher activity in DCB-habituated cells. Some of the isoPOXs detected could be
      involved in cross-linking of arabinoxylans and in the lignin-like polymer
      formation in DCB-habituated cells.

PMID- 29464728
TI  - Aluminum oxo-fluoride clusters: A first principle investigation of stability,
      synthetic considerations, and the interaction with water.
AB  - The introduction of the so called fluorolytic sol-gel synthesis in 2003 gave
      access to previously inaccessible aluminum oxo-fluorides, thus to nanoscopic
      materials and, more importantly, novel catalysts. The intermediate cluster
      structures synthesized and stabilized by Kemnitz and coworkers have mainly been
      protected by iso-propoxide groups. However, since catalytic reactions take place
      in a large variety of media, hydrophilic analogs of those clusters would be of
      interest. In this manuscript, we present a computational analysis for the
      fluorination reaction, which represents the second part of fluorolytic sol-gel
      synthesis, and a theoretical study of the synthesized Al4 F4 (MU4 -O)(MU-Oi Pr)5
      [H(Oi Pr)2 ] nanostructure's conversion to its hydroxylated analog Al4 F4 (MU4 
      O)(MU-OH)5 [H(OH)2 ] utilizing the nudged elastic band method. Furthermore, the
      role of the fluorine atoms of the cluster in an aqueous medium is evaluated by
      studying the incremental addition of water molecules to the cluster with and
      without fluorine atoms. In addition, NMR shifts of clusters exhibiting different
      substituents are compared. It has been found that the inclusion of an explicit
      solvent is necessary to capture the magnetic response of the individual cluster
      atoms in an aqueous solvent correctly. (c) 2018 Wiley Periodicals, Inc.

PMID- 29464729
TI  - Establishing a sensitive capillary electrophoresis-UV method for direct
      determination of amino acids to evaluate vinegar quality.
AB  - In this study, the capillary electrophoresis method with ultraviolet detection
      was established to directly determine amino acids in vinegar, according to the
      coordination interaction between amino acids (AAs) and copper ions. The online
      sweeping technique was combined to improve the detection sensitivity. The quality
      of vinegar was evaluated with AAs as parameters by United Nations Food
      Agriculture Organization/Word Health Organization AAs model and principal
      component analysis. Optimum conditions were obtained under 50 mM CuSO4 and
      adjusted pH 4.40 with 8 mM acetate, 70 s injection time, 22.5 kV separation
      voltage, and 254 nm detected wavelength. Method validation, indicating good
      linearity (R2  > 0.9989), precision with an RSD less than 8.0% (n = 5), LOD (0.13
      0.25 MUg/mL), LOQ (0.43-0.83 MUg/mL) and recovery (80.5-112.6%). Under the
      optimal conditions, AAs in vinegar can be directly separated which is propitious
      for the quality evaluation of vinegar.

PMID- 29464730
TI  - Demyelination during anti-tumour necrosis factor therapy for psoriasis.
AB  - Anti-tumour necrosis factor (anti-TNF) therapies have been associated with
      neurological complications, including in rare cases demyelinating disease. It is
      currently unknown whether patients who have received more than one
      immunosuppressive agent or anti-TNF have a greater risk of demyelination. We
      report the case of a 37-year-old woman with psoriasis who presented with an acute
      episode of demyelination while on anti-TNF therapy. This case was complicated by
      the fact that progressive multifocal leukoencephalopathy was considered the
      likely diagnosis initially and was only definitively excluded by brain biopsy.
      This case demonstrates the difficulty establishing the correct diagnosis in
      patients with atypical presentations on immunomodulating therapies. We present
      this rare case of demyelination in a patient who received multiple
      immunosuppressive therapies to highlight this challenging clinical situation and
      discuss management with a literature review.

PMID- 29464731
TI  - Progressive osseous heteroplasia caused by a mosaic GNAS mutation.

PMID- 29464732
TI  - Was 4beta-hydroxycholesterol ever going to be a useful marker of CYP3A4 activity?

PMID- 29464733
TI  - CAMERRA: An analysis tool for the computation of conformational dynamics by
      evaluating residue-residue associations.
AB  - A computational method which extracts the dominant motions from an ensemble of
      biomolecular conformations via a correlation analysis of residue-residue contacts
      is presented. The algorithm first renders the structural information into contact
      matrices, then constructs the collective modes based on the correlated dynamics
      of a selected set of dynamic contacts. Associated programs can bridge the results
      for further visualization using graphics software. The aim of this method is to
      provide an analysis of conformations of biopolymers from the contact viewpoint.
      It may assist a systematical uncovering of conformational switching mechanisms
      existing in proteins and biopolymer systems in general by statistical analysis of
      simulation snapshots. In contrast to conventional correlation analyses of
      Cartesian coordinates (such as distance covariance analysis and Cartesian
      principal component analysis), this program also provides an alternative way to
      locate essential collective motions in general. Herein, we detail the algorithm
      in a stepwise manner and comment on the importance of the method as applied to
      decoding allosteric mechanisms. (c) 2018 Wiley Periodicals, Inc.

PMID- 29464734
TI  - Prevalence of potential sexual abuse in adolescents and young adults and
      feasibility of an assessment and management plan used in three research projects.
AB  - The aims of this study were to examine the feasibility of a protocol to assess
      for assessment and response to potential sexual abuse (defined as self-report of
      sexual initiation before age 13) among adolescent and young adult research
      participants in human papillomavirus (HPV) vaccination screening; determine the
      proportion of participants whose survey responses indicated potential sexual
      abuse and assess whether age, gender, race, and recruitment site were associated
      with potential abuse. We pooled data from three cross-sectional studies of 13-26
      year-old women and men (N = 1541) recruited at a Teen Health Center (THC) and
      Health Department (HD). Using written and electronic documentation, we
      demonstrated feasibility by the following outcomes: 100% of participants who
      indicated early sexual initiation were interviewed by the research staff, 100% of
      assessments were disclosed to participants' primary care clinicians, and no
      adverse consequences of the interviews or referrals occurred. Potential sexual
      abuse was identified in 95 participants (6.2%). In multivariable logistic
      regression, the following factors were independently associated with potential
      abuse: race (Black vs. White, odds ratio [OR] = 3.0, 95% confidence interval [CI]
      = 1.6-5.7; other race vs. White, OR = 2.6, 95%CI = 1.0-6.5); and recruitment site
      (HD vs. THC, OR = 2.1, 95%CI = 1.4-3.3). The standardized protocol to identify,
      assess and refer youth who may have been sexually abused was feasible and can
      enable researchers to ensure the safety of study participants.

PMID- 29464735
TI  - molUP: A VMD plugin to handle QM and ONIOM calculations using the gaussian
      software.
AB  - The notable advances obtained by computational (bio)chemistry provided its
      widespread use in many areas of science, in particular, in the study of reaction
      mechanisms. These studies involve a huge number of complex calculations, which
      are often carried out using the Gaussian suite of programs. The preparation of
      input files and the analysis of the output files are not easy tasks and often
      involve laborious and complex steps. Taking this into account, we developed
      molUP: a VMD plugin that offers a complete set of tools that enhance the
      preparation of QM and ONIOM (QM/MM, QM/QM, and QM/QM/MM) calculations. The
      starting structures for these calculations can be imported from different
      chemical formats. A set of tools is available to help the user to examine or
      modify any geometry parameter. This includes the definition of layers in ONIOM
      calculations, choosing fixed atoms during geometry optimizations, the
      recalculation or adjustment of the atomic charges, performing SCANs or IRC
      calculations, etc. molUP also extracts the geometries from the output files as
      well as the energies of each of them. All of these tasks are performed in an
      interactive GUI that is extremely helpful for the user. MolUP was developed to be
      easy to handle by inexperienced users, but simultaneously to be a fast and
      flexible graphical interface to allow the advanced users to take full advantage
      of this plugin. The program is available, free of charges, for macOS, Linux, and
      Windows at the PortoBioComp page
      https://www.fc.up.pt/PortoBioComp/database/doku.php?id=molup. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29464736
TI  - Molecular dynamics coupled with a virtual system for effective conformational
      sampling.
AB  - An enhanced conformational sampling method is proposed: virtual-system coupled
      canonical molecular dynamics (VcMD). Although VcMD enhances sampling along a
      reaction coordinate, this method is free from estimation of a canonical
      distribution function along the reaction coordinate. This method introduces a
      virtual system that does not necessarily obey a physical law. To enhance sampling
      the virtual system couples with a molecular system to be studied. Resultant
      snapshots produce a canonical ensemble. This method was applied to a system
      consisting of two short peptides in an explicit solvent. Conventional molecular
      dynamics simulation, which is ten times longer than VcMD, was performed along
      with adaptive umbrella sampling. Free-energy landscapes computed from the three
      simulations mutually converged well. The VcMD provided quicker
      association/dissociation motions of peptides than the conventional molecular
      dynamics did. The VcMD method is applicable to various complicated systems
      because of its methodological simplicity. (c) 2018 Wiley Periodicals, Inc.

PMID- 29464737
TI  - Copeptin role in polyuria-polydipsia syndrome differential diagnosis and
      reference range in paediatric age.
AB  - OBJECTIVE: Plasma arginine-vasopressin (AVP) analysis can help in the
      differential diagnosis of the polyuria-polydipsia syndrome (PPS), even if such
      investigation is hampered by technical difficulties, conversely to its surrogate
      copeptin. This study aims to enlarge the existing data on normal copeptin levels
      in childhood, to evaluate the correlation between copeptin, serum sodium and
      plasma and urine osmolality, and to assess the utility of the copeptin analysis
      in the diagnostic work-up of PPS in the paediatric age. PATIENTS AND METHODS:
      Plasma copeptin levels were evaluated in 53 children without AVP disorders
      (control population), in 12 hypopituitaric children and in 15 patients with PPS
      after water deprivation test (WDT). RESULTS: Mean basal copeptin levels were 5.2
      +/- 1.56 (range 2.4-8.6 pmol/L) in the control population, 2.61 +/- 0.49 pmol/L
      in the hypopituitaric children with complete diabetes insipidus (CDI) (P = .04)
      and 6.21 +/- 1.17 pmol/L in the hypopituitaric patients without DI (P = .02).
      After WDT, among 15 naive polyuric/polydipsic children, copeptin values greater
      than 20 pmol/L allowed to identify nephrogenic diabetes insipidus (NDI),
      concentrations below 2.2 pmol/L complete central DI (CCDI) and between 5 and 20
      pmol/L primary polydipsia (PP). Copeptin cut-off level of 3.5 pmol/L
      distinguished CDI from PP, with a sensitivity and specificity of 75% and 83.3%,
      respectively. CONCLUSION: Copeptin evaluation holds promises as a diagnostic tool
      in paediatric PPS; its interpretation might be useful to promptly distinguish
      NDI, even avoiding the WDT need.

PMID- 29464739
TI  - Trigger bond analysis of nitroaromatic energetic materials using wiberg bond
      indices.
AB  - The identification of trigger bonds, bonds that break to initiate explosive
      decomposition, using computational methods could help direct the development of
      novel, "green" and efficient high energy density materials (HEDMs). Comparing
      bond densities in energetic materials to reference molecules using Wiberg bond
      indices (WBIs) provides a relative scale for bond activation (%DeltaWBIs) to
      assign trigger bonds in a set of 63 nitroaromatic conventional energetic
      molecules. Intramolecular hydrogen bonding interactions enhance contributions of
      resonance structures that strengthen, or deactivate, the C?NO2 trigger bonds and
      reduce the sensitivity of nitroaniline-based HEDMs. In contrast, unidirectional
      hydrogen bonding in nitrophenols strengthens the bond to the hydrogen bond
      acceptor, but the phenol lone pairs repel and activate an adjacent nitro group.
      Steric effects, electron withdrawing groups and greater nitro dihedral angles
      also activate the C?NO2 trigger bonds. %DeltaWBIs indicate that nitro groups
      within an energetic molecule are not all necessarily equally activated to
      contribute to initiation. %DeltaWBIs generally correlate well with impact
      sensitivity, especially for HEDMs with intramolecular hydrogen bonding, and are a
      better measure of trigger bond strength than bond dissociation energies (BDEs).
      However, the method is less effective for HEDMs with significant secondary
      effects in the solid state. Assignment of trigger bonds using %DeltaWBIs could
      contribute to understanding the effect of intramolecular interactions on
      energetic properties. (c) 2018 Wiley Periodicals, Inc.

PMID- 29464738
TI  - Heterozygous aggrecan variants are associated with short stature and
      brachydactyly: Description of 16 probands and a review of the literature.
AB  - OBJECTIVE: Mutations in the aggrecan gene (ACAN) have been identified in two
      autosomal dominant skeletal dysplasias, spondyloepiphyseal dysplasia, Kimberley
      type (SEDK), and osteochondritis dissecans, as well as in a severe recessive
      dysplasia, spondyloepimetaphyseal dysplasia, aggrecan type. Next-generation
      sequencing (NGS) has aided the identification of heterozygous ACAN mutations in
      individuals with short stature, minor skeletal defects and mild facial
      dysmorphisms, some of whom have advanced bone age (BA), poor pubertal spurt and
      early growth cessation as well as precocious osteoarthritis. DESIGN AND METHODS:
      This study involves clinical and genetic characterization of 16 probands with
      heterozygous ACAN variants, 14 with short stature and mild skeletal defects
      (group 1) and two with SEDK (group 2). Subsequently, we reviewed the literature
      to determine the frequency of the different clinical characteristics in ACAN
      positive individuals. RESULTS: A total of 16 ACAN variants were located
      throughout the gene, six pathogenic mutations and 10 variants of unknown
      significance (VUS). Interestingly, brachydactyly was observed in all probands.
      Probands from group 1 with a pathogenic mutation tended to be shorter, and 60%
      had an advanced BA compared to 0% in those with a VUS. A higher incidence of coxa
      valga was observed in individuals with a VUS (37% vs 0%). Nevertheless, other
      features were present at similar frequencies. CONCLUSIONS: ACAN should be
      considered as a candidate gene in patients with short stature and minor skeletal
      defects, particularly those with brachydactyly, and in patients with
      spondyloepiphyseal dysplasia. It is also important to note that advanced BA and
      osteoarticular complications are not obligatory conditions for
      aggrecanopathies/aggrecan-associated dysplasias.

PMID- 29464740
TI  - The Current State of Ultrasound Training in Obstetrics and Gynecology Residency
      Programs.
AB  - OBJECTIVES: We evaluated the current state of ultrasound training in obstetrics
      and gynecology (OB-GYN) residency programs across the United States. METHODS: An
      electronic survey was sent to OB-GYN residency program directors and OB-GYN
      residents. Responses were obtained in September 2016. Program directors and
      residents were asked to reflect on their current ultrasound curriculum. RESULTS:
      A total of 93 program directors and 437 residents responded. Respondents were
      mostly from university programs located in tertiary centers. Ultrasound curricula
      varied: 11% of program directors and 23% of residents did not have any ultrasound
      related didactics; of those who did, 27% of program directors and 40% of
      residents had it yearly or less. Three-quarters had mandatory ultrasound
      rotations, and few offered ultrasound electives (program directors, 52%;
      residents, 28%). Most residents were required to perform ultrasound examinations
      daily or weekly (98%). Most stated that the main focus of the rotation was OB
      only. Skill was evaluated mainly subjectively by direct observation. Although
      most program directors stated that residents were satisfactory/excellent in
      ultrasound, 22% would not treat patients on the basis of ultrasound examinations
      performed by their senior residents. Similarly, of all postgraduate year 4
      respondents (n = 86), 76% stated that they will require additional training to be
      able to perform or read ultrasound examinations independently, and 43% would not
      treat a patient on the basis of their own ultrasound examinations without further
      confirmation. Residents believed that the biggest obstacle in ultrasound training
      is lack of dedicated faculty time (41%). CONCLUSIONS: Recognizing the lack of
      clearly defined milestones in ultrasound training in OB-GYN residency, this study
      confirms the substantial heterogeneity in curricula between programs,
      highlighting a need for a standardized ultrasound curriculum.

PMID- 29464741
TI  - Accuracy of adrenal computed tomography in predicting the unilateral subtype in
      young patients with hypokalaemia and elevation of aldosterone in primary
      aldosteronism.
AB  - CONTEXT: The current Endocrine Society Guideline suggests that patients aged <35
      years with marked primary aldosteronism (PA) and unilateral adrenal lesions on
      adrenal computed tomography (CT) scan may not need adrenal vein sampling (AVS)
      before proceeding to unilateral adrenalectomy. This suggestion is, however, based
      on the data from only one report in the literature. OBJECTIVE: We sought to
      determine the accuracy of CT findings in young PA patients who had unilateral
      adrenal disease on CT with hypokalaemia and elevation of aldosterone. DESIGN AND
      PATIENTS: We retrospectively studied 358 PA patients (n = 30, aged <35 years; n =
      39, aged 35-40 years; n = 289, aged >=40 years) with hypokalaemia and elevation
      of aldosterone and unilateral disease on CT who had successful AVS. MAIN OUTCOME
      MEASURE: Accuracy of CT findings is determined by AVS findings and/or surgical
      outcomes in patients aged <35 years. RESULTS: Concordance of the diagnosis
      between CT and AVS was 90% (27/30) in patients aged <35 years, 79% (31/39) in
      patients aged 35-40 years and 69% (198/289) in those aged >=40 years (trend for P
      < .01). Surgical benefit was confirmed in three patients aged <35 years and in
      three patients aged 35-40 years with the available surgical data who had
      discordance between CT and AVS findings. Collectively, the diagnostic accuracy of
      CT findings was 100% (30/30) if aged <35 years and 87% (34/39) if aged 35-40
      years. CONCLUSION: Primary aldosteronism patients aged <35 years with
      hypokalaemia and elevation of aldosterone and unilateral disease on adrenal CT
      could be spared AVS.

PMID- 29464742
TI  - GdX/UBL4A null mice exhibit mild kyphosis and scoliosis accompanied by
      dysregulation of osteoblastogenesis and chondrogenesis.
AB  - GdX, also named ubiquitin-like protein 4A, is a ubiquitin-domain protein
      characterized by a ubiquitin-like domain that regulates the movement of misfolded
      proteins from the endoplasmic reticulum membrane to proteasome. However, its
      function in skeletal biology remains unclear. Here, we report that GdX plays a
      crucial role in skeletal development as mice lacking GdX exhibit skeletal
      dysplasias, mild kyphosis, and scoliosis. During embryonic stage, GdX knockout
      mice display decreased bone mineral density and trabecular bone accompanied by
      delayed osteogenic formation. GdX knockout mice also have blended spine and small
      body size. At the molecular level, GdX knockout mice showed perturbed expression
      of osteogenesis-related genes and cartilage developmental genes, indicative of
      altered differentiation of mesenchymal cell lineage. Collectively, our results
      uncovered GdX as a novel regulator in bone development and a potential candidate
      gene for skeletal dysplasias.

PMID- 29464743
TI  - Micellar polymerization: Computer simulations by dissipative particle dynamics.
AB  - Nowadays, micellar polymerization is widely used in different fields of industry
      and research, including modern living polymerization technique. However, this
      process has many variables and there is no comprehensive model to describe all
      features. This research presents simulation methodology which describes key
      properties of such reactions to take a guide through a variety of their
      modifications. Dissipative particle dynamics is used in addition to Monte Carlo
      scheme to simulate initiation, propagation, and termination events. Influence of
      initiation probability and different termination processes on final conversion
      and molecular-weight distribution are presented. We demonstrate that prolonged
      initiation leads to increasing in polymer average molecular weight, and surface
      termination events play major role in conversion limitation, in comparison with
      recombination. (c) 2018 Wiley Periodicals, Inc.

PMID- 29464744
TI  - Primary peri-anal adenocarcinoma of intestinal type - a new proposed entity.
AB  - AIMS: The currently recognised subtypes of anal canal/peri-anal adenocarcinoma
      are those arising from low rectal mucosa or columnar cuff, fistula-related
      tumours and anal gland carcinoma. This report presents two examples of a hitherto
      undescribed subtype of peri-anal adenocarcinoma with an intestinal phenotype.
      METHODS AND RESULTS: A 74-year-old man had a peri-anal tumour locally excised,
      whereas a 73-year-old female underwent an abdominoperineal resection for peri
      anal Paget's disease with an underlying carcinoma. Neither patient had a history
      of perineal fistulae, Crohn's disease or previous gastrointestinal neoplasia, and
      neither showed clinical, radiological or endoscopic evidence of another abdominal
      or pelvic tumour. Both resection specimens contained adenocarcinoma, which were
      similar in demonstrating an intestinal morphology and CDX2 immunopositivity. The
      man has shown a disease-free outcome thus far, but the woman has suffered with
      nodal and pelvic recurrence within a few months of surgery. CONCLUSIONS: The name
      'primary peri-anal adenocarcinoma of intestinal type' is proposed for this
      previously unrecognised subtype of perineal neoplasia. Awareness of its distinct
      existence - by recognising its intestinal morphology and immunophenotype while
      excluding metastasis from the intestinal tract - should help to collate data to
      determine its specific prognosis and to formulate its best management.

PMID- 29464745
TI  - Effects of a prevention program for internet addiction among middle school
      students in South Korea.
AB  - OBJECTIVES: This study explored the effects of a self-regulatory efficacy
      improvement program on self-control, self-efficacy, internet addiction, and time
      spent on the internet among middle school students in South Korea. The program
      was led by school nurses, and it is integrated self-efficacy and self-regulation
      promotion strategies based on Bandura's social cognitive theory. DESIGN AND
      SAMPLE: A quasi-experimental, nonequivalent, control group, pre-posttest design
      was used. The participants were 79 middle school students. MEASURES: Measurements
      included the Self-Control Scale, Self-Efficacy Scale, Internet Addiction
      Proneness Scale, and an assessment of internet addiction. RESULTS: Self-control
      and self-efficacy significantly increased and internet addiction and time spent
      on the internet significantly decreased in the intervention group compared with
      the control group. CONCLUSION: A program led by school nurses that integrated and
      applied self-efficacy and self-regulation intervention strategies proved
      effective for prevention of students' internet addiction.

PMID- 29464746
TI  - Basal cell carcinoma induced by therapeutic radiation for tinea capitis
      clinicopathological study.
AB  - AIMS: An increased prevalence of aggressive histological subtypes, such as
      micronodular and morpheaform, has been seen, irrespective of the clinical course,
      in basal cell carcinoma (BCC) following irradiation for tinea capitis. The aim of
      this study was to assess the histopathological features of BCCs among patients
      irradiated for tinea capitis and correlate them with the clinical course. METHODS
      AND RESULTS: The medical records and BCC biopsy specimens of individuals who were
      previously irradiated for tinea capitis were reviewed. Demographic data and
      clinical characteristics were retrieved. Biopsy specimens were evaluated for
      histological subtype classification and additional histopathological features. A
      telephone survey was conducted to assess the clinical behaviour of the tumours.
      Thirty-one patients (17 male; 14 female) were included. The average age at time
      of first biopsy was 56 years. The total number of lesions was 185, with 80% of
      subjects showing multiple lesions. The nodular subtype was the most prevalent,
      followed by superficial, micronodular and mixed tumours. One-third of the BCCs
      could be classified as aggressive histologically. Stromal fibroplasia and melanin
      deposits were common. There was no mortality related to BCC. None of the 17
      patients who completed the survey had evidence of local invasiveness or
      metastases. CONCLUSIONS: BCCs following radiation therapy for tinea capitis show
      unique histological characteristics related to aggressive behaviour. These
      aggressive features did not reflect the clinical behaviour in the current cohort.

PMID- 29464747
TI  - Tarsal attachment devices of the southern green stink bug Nezara viridula
      (Heteroptera: Pentatomidae).
AB  - Based on analyses with cryo-scanning and transmission electron microscopy, the
      present study reports on the morphology and ultrastructure of the attachment
      structures of the green stinkbug Nezara viridula L. (Heteroptera: Pentatomidae),
      a cosmopolitan pest of different crops in most areas of the world. In addition,
      the presence and distribution of large proportions of the elastic protein resilin
      in these structures was revealed by confocal laser scanning microscopy. The
      attachment structures of each leg comprise two sclerotised claws, a pair of
      smooth flexible pulvilli and a hairy adhesive pad located at the ventral side of
      the basitarsus. No sexual dimorphism is evident. Contact areas of resting
      individuals on a smooth surface show that N. viridula creates contact to the
      substrate with the ventral surface of (a) the distal portions of the pulvilli,
      (b) the setae of the hairy adhesive pad, (c) the two paraempodia representing
      mechanosensory setae, and (d) the tips of the claws. Each pulvillus is a sac-like
      structure formed by complex cuticular layers that vary in their structure and
      resilin content. The dorsal side consists of sclerotised chitinous material,
      while the ventral cuticle consists mainly of resilin and shows a very thin
      epicuticle and a thick exocuticle. The setae of the hairy adhesive pad are
      pointed and socketed. They exhibit a pronounced longitudinal gradient in the
      material composition, with large proportions of resilin being present in the
      setal tips. In most of these setae, especially in those of the distal-most part
      of the pad, also a transverse gradient in the material composition is visible.

PMID- 29464748
TI  - Prospective randomized study evaluating ultrasound versus fluoroscopy guided
      sacral InterStim(r) lead placement: A pilot study.
AB  - OBJECTIVE: To investigate the use of intraoperative ultrasound during stage I
      InterStim(r) sacral lead placement. METHODS: A total of 40 patients were randomly
      assigned to undergo InterStim(r) lead placement utilizing fluoroscopy or
      ultrasound guidance. Patients were blinded for the duration of the study. The
      surgeon and staff were blinded until after induction of anesthesia. Patients met
      criteria for refractory overactive bladder, fecal incontinence, or both. The ICIQ
      OABqol, OABSS, and FIQL validated questionnaires were used pre- and post
      operatively. Primary endpoint was total fluoroscopy time. Secondary endpoints
      were total radiation exposure and total number of foramen needle skin punctures.
      RESULTS: Forty patients were enrolled, twenty in the ultrasound and twenty in the
      fluoroscopy only arm. Mean age was 60 (SD = 14.4) and mean BMI 32 (SD = 7.2).
      Twenty-seven patients (67.5%) had urinary symptoms, four (10%) fecal
      incontinence, and nine (22.5%) had mixed symptoms. Radiation exposure time was
      reduced by 70.5 s (P = 0.002), radiation exposure was decreased by 42.3 mGy (P =
      0.017), and the number of needle skin punctures decreased by 3.6 (P = 0.035) with
      use of ultrasound. Mean OR time in minutes was 55.5 in ultrasound and 58.2 in
      fluoroscopy group (P = 0.53). There were no statistically significant differences
      in questionnaire scores between groups. CONCLUSION: Ultrasound guided placement
      of foramen needle during Stage I sacral neuromodulation results in reduction of
      radiation exposure to the patient, surgeon, and operating room staff. Further
      studies are necessary to determine the learning curve and efficacy of this
      technique.

PMID- 29464749
TI  - Intraarticular injection autologous platelet-rich plasma and bone marrow
      concentrate in a goat osteoarthritis model.
AB  - To evaluate the effects of intraarticular injections of autologous platelet-rich
      plasma (PRP) or bone marrow concentrate (BMC) on osteoarthritis (OA), 24 adult
      goats were equally divided into control (Ctrl), saline (NS), PRP, and BMC groups,
      and OA was induced by surgery in NS, PRP, and BMC groups. Autologous PRP and BMC
      were obtained from whole blood and bone marrow aspirates, respectively. The data
      revealed, platelets were increased in BMC by 1.8-fold, monocytes by 5.6-fold, TGF
      beta1 by 7.7-fold, and IGF-1 by 3.6-fold (p < 0.05), and platelets were increased
      in PRP by 2.9-fold, and TGF-beta1 by 3.3-fold (p < 0.05). From the sixth week
      post-operation, saline, PRP, and BMC were administered by intraarticular
      injection once every 4 weeks, three consecutive times. After the animals were
      sacrificed, inflammatory cytokines in the synovial fluid was measured, and bone
      and cartilage degeneration progression was observed by macroscopy, histology, and
      immunohistochemistry. Compared with the NS group, the level of inflammatory
      cytokines was reduced in the PRP and BMC groups (p < 0.05). Histologically,
      delayed cartilage degeneration and higher levels of extracellular matrix (ECM)
      were observed in both PRP and BMC treated groups (p < 0.05). Furthermore, the BMC
      group showed greater cartilage protection and less ECM loss than the PRP group (p
      < 0.05). In summary, this study showed that intraarticular injection of
      autologous PRP and BMC has therapeutic efficacy in a goat osteoarthritis model,
      with the greater benefit in terms of cartilage protection being observed in the
      BMC-treated group than PRP. (c) 2018 Orthopaedic Research Society. Published by
      Wiley Periodicals, Inc. J Orthop Res.

PMID- 29464750
TI  - Inhibition of ADAM10 in satellite cells accelerates muscle regeneration following
      muscle injury.
AB  - Muscle injury is one of the most common orthopedic and sports disorders. For
      severe cases, surgical repair may be indicated; however, other than
      immobilization and the administration of anti-inflammatory drugs there is
      currently no effective conservative treatment for this condition. Satellite cells
      (SCs) are muscle-specific stem cells and are indispensable for muscle
      regeneration after muscle injury. SCs are activated upon muscle injury to
      proliferate and differentiate into myoblasts, which subsequently fuse into
      myofibers and regenerate the damaged muscle. We have previously shown that
      ADAM10, a membrane-anchored proteolytic enzyme, is essential for the maintenance
      of SC quiescence by activating the Notch signaling pathway in SCs. Because
      suppression of ADAM10 activity in SCs can activate SC differentiation, we asked
      whether inactivation of ADAM10 in SCs after muscle injury could enhance muscle
      regeneration. Using Adam10 conditional knockout mice, in which ADAM10 activity
      can specifically be suppressed in SCs, we found that partial inactivation of
      ADAM10 accelerates muscle regeneration after muscle injury. Nearly identical
      results were obtained by the administration of GI254023X, a selective ADAM10
      inhibitor. The findings of the present study thus indicate that transient
      enhancement of SC differentiation after muscle injury expedites muscle
      regeneration and that ADAM10 can be a potential molecular target in treating
      muscle injuries. (c) 2018 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res.

PMID- 29464751
TI  - Prediction of bladder outcomes after ischemic spinal cord injury: A longitudinal
      cohort study from the European multicenter study about spinal cord injury.
AB  - OBJECTIVE: The recovery of bladder function after spinal cord injury (SCI) is of
      major importance for patients and caregivers. We recently developed prediction
      models of bladder outcomes (defined as the capacity of storing the urine and
      emptying completely the bladder) 1 year after a SCI of traumatic etiology and
      investigated if these models would also be applicable to patients with ischemic
      SCI. PATIENTS AND METHODS: From the European multicenter study about spinal cord
      injury (EMSCI), we extracted data of all ischemic SCI patients with available
      neurological and functional data (according to the International Standards for
      Neurological Classification of Spinal Cord Injury, ISNCSCI, and Spinal Cord
      Independence Measure, SCIM) within 40 days and bladder outcomes 1 year after
      ischemia. The model relies on three predictors: strength of the legs, the
      presence of sensation in the S3 dermatome, and the part of the SCIM assessing
      breathing and bladder and bowel control. A simplified model relying on leg
      strength only was also tested. Bladder outcomes were evaluated according to the
      score of item six of SCIM. RESULTS: In total 85 patients (56 males (66%), mean
      age 55 years) were included. Twenty-three patients (27%) showed complete bladder
      function recovery one year after ischemia. Both models showed a very good
      predictive power: the area under the receiver operating characteristics curve
      (aROC) of the two models was 0.825 and 0.822, respectively. CONCLUSIONS:
      Comparable to acute traumatic SCI, also in ischemic SCI the outcome of full
      bladder function recovery can be predicted by clinical scores, and prediction
      models of bladder outcomes may be applicable in clinical trials.

PMID- 29464752
TI  - Voluntary wheel running attenuates urinary bladder hypersensitivity and
      dysfunction following neonatal maternal separation in female mice.
AB  - AIMS: Patients with interstitial cystitis/painful bladder syndrome (IC/PBS)
      commonly suffer from widespread pain and mood disorder, which has been attributed
      to improper functioning of the hypothalamic-pituitary-adrenal (HPA) axis.
      Voluntary exercise has been shown to improve HPA axis function, therefore we are
      determining whether voluntary wheel running can attenuate urological pain and
      dysfunction following neonatal maternal separation (NMS) in female mice. METHODS:
      Mice underwent NMS for 3 h/day from postnatal Day 1-21, were caged with free
      access to running wheels at 4 weeks of age, and assessed 4 weeks later for
      bladder sensitivity, micturition, reward behavior, mast cell degranulation, and
      HPA axis-related in vitro analysis. RESULTS: Increased bladder sensitivity, void
      frequency, and mast cell degranulation was observed in adult sedentary (-Sed) NMS
      mice, compared to naive-Sed controls. Sucrose preference was increased in NMS-Sed
      mice and corticotropin-releasing factor receptor 1 (CRF1 ) and glucocorticoid
      receptor mRNA levels were significantly reduced in the hippocampus. Exercise
      normalized bladder sensitivity, micturition output, and increased brain-derived
      neurotrophic factor (BDNF) mRNA levels in the hippocampus of NMS mice. Mast cell
      degranulation was also normalized in NMS bladders following exercise.
      CONCLUSIONS: Voluntary exercise normalized behavioral outcomes resulting from NMS
      in female mice, increased hippocampal BDNF mRNA levels, and decreased mast cell
      degranulation in the bladder. Together these results provide novel insight into
      the efficacy of voluntary exercise to attenuate comorbid outcomes resulting from
      exposure to early life stress.

PMID- 29464754
TI  - Development of the duct system during exocrine pancreas differentiation in the
      grass snake Natrix natrix (Lepidosauria, Serpentes).
AB  - We analyzed the development of the pancreatic ducts in grass snake Natrix natrix
      L. embryos with special focus on the three-dimensional (3D)-structure of the duct
      network, ultrastructural differentiation of ducts with attention to cell types
      and lumen formation. Our results indicated that the system of ducts in the
      embryonic pancreas of the grass snake can be divided into extralobular,
      intralobular, and intercalated ducts, similarly as in other vertebrate species.
      However, the pattern of branching was different from that in other vertebrates,
      which was related to the specific topography of the snake's internal organs. The
      process of duct remodeling in Natrix embryos began when the duct walls started to
      change from multilayered to single-layered and ended together with tube
      formation. It began in the dorsal pancreatic bud and proceeded toward the caudal
      direction. The lumen of pancreatic ducts differentiated by cavitation because a
      population of centrally located cells was cleared through cell death resembling
      anoikis. During embryonic development in the pancreatic duct walls of the grass
      snake four types of cells were present, that is, principal, endocrine, goblet,
      and basal cells, which is different from other vertebrate species. The principal
      cells were electron-dense, contained indented nuclei with abundant
      heterochromatin, microvilli and cilia, and were connected by interdigitations of
      lateral membranes and junctional complexes. The endocrine cells were electron
      translucent and some of them included endocrine granules. The goblet cells were
      filled with large granules with nonhomogeneous, moderately electron-dense
      material. The basal cells were small, electron-dense, and did not reach the duct
      lumen.

PMID- 29464753
TI  - Grade 4 asbestosis does not extend directly from the respiratory bronchiole to
      the peripheral lung.
AB  - AIMS: To confirm whether or not grade 4 asbestosis progresses from the
      respiratory bronchiole to the peripheral lung. METHODS AND RESULTS: We examined
      retrospectively the autopsy or lobectomy specimens from 31 cases (29 males; mean
      age 64 years) satisfying the pathological criteria of grade 4 asbestosis.
      Asbestos bodies (ABs) were quantified in samples of dissolved lung and in tissue
      preparations on glass slides. Respiratory bronchiolar lesions were graded as 0, 1
      and >=2. Grade 4 asbestosis was subdivided into an atelectatic induration (AI)
      and usual interstitial pneumonia pattern (UIP pattern). Five, 10, and 16 cases
      had grades 0, 1 or >=2 lesions, respectively, with mean respective numbers of ABs
      in dissolved lung of 117 000/g dry lung, 468 000/g and 968 000/g; and in
      specimens on glass slides of seven ABs/cm2 of tissue slice, 34 ABs /cm2 and 195
      ABs /cm2 . The differences were significant. Fifteen and 16 cases showed AI and
      UIP patterns, respectively, with mean respective numbers of ABs in dissolved lung
      of 1 006 000/g dry lung and 354 000/g, and 186 and 56 ABs/cm2 on glass slides.
      The differences were significant. AI patterns originated in subpleural lobules or
      subpleural zonal areas and UIP patterns originated in subpleural, peripheral
      lobules. CONCLUSIONS: Grade 4 asbestosis does not start in the respiratory
      bronchiole. The presence of a grade 1 lesion is not required for the diagnosis of
      grade 4 asbestosis.

PMID- 29464755
TI  - Safety and efficacy of nivolumab in Japanese patients with malignant melanoma: An
      interim analysis of a postmarketing surveillance.
AB  - A postmarketing surveillance study is ongoing to evaluate nivolumab treatment for
      Japanese patients with malignant melanoma and accumulate data on all adverse
      events (AE) and efficacy. In this interim analysis, we evaluated data from
      approximately 100 Japanese medical institutions obtained from the nivolumab
      approval date in Japan (4 July 2014) through 3 July 2016. Patients were monitored
      during the first 12 months of treatment. Nivolumab was administrated by i.v.
      infusion (2 mg/kg every 3 weeks). A total of 680 and 610 patients were evaluated
      for safety and efficacy, respectively. The incidences of adverse drug reactions
      (ADR) and grade 3 or higher ADR were 53.53% and 12.35%, respectively. Predominant
      ADR included hypothyroidism (11.32%) and abnormal enzyme activity, such as
      increase of aspartate aminotransferase (7.79%), alanine aminotransferase (6.76%),
      alkaline phosphatase (6.18%) and gamma-glutamyltransferase (5.44%). Grade 3 or
      higher ADR of special interest with an incidence of 1% or higher were hepatic
      function disorder (2.50%), colitis/diarrhea (2.06%) and infusion reaction
      (1.32%). No cases of encephalitis or venous thromboembolism, other AE of special
      interest, were observed. The estimated median overall survival was 379 days (95%
      confidence interval [CI], 290-not reached [NR]) in the overall population, NR
      (95% CI, 305-NR) for cutaneous melanoma and 340 days (95% CI, 275-NR) for mucosal
      melanoma. The improvement rate based on the antitumor response at the last
      evaluation was 22.2% (131/590 patients). No new safety concerns were raised, and
      serious ADR of special interest were infrequent. Nivolumab showed equivalent
      efficacy in patients with mucosal melanoma and those with cutaneous melanoma.

PMID- 29464756
TI  - Impact on quality of life and sexual satisfaction of continent cystostomy with
      enterocystoplasty in an adult neurologic population.
AB  - AIMS: To evaluate long-term general and urinary quality of life (QOL) and sexual
      satisfaction in adult neurologic patients undergoing continent cystostomy surgery
      associated with a bladder enlargement to treat neurogenic lower urinary tract
      dysfunction. METHODS: Monocentre, retrospective series of adult neurologic
      patients who underwent continent cystostomy with bladder enlargement and followed
      up in the long-term. We assessed during follow-up, urinary and renal function and
      patients filled QOL questionnaires on general QOL, sexuality and urinary (short
      form Qualiveen) disability. RESULTS: Fifty-three patients were included and
      followed-up 77 months on average. Rates of patients' satisfaction, stomal and
      urethral continences were respectively of 98.7% (n = 51), 94.1% (n = 48), and
      80.4% (n = 41). Impact of surgery on general QOL and autonomy were strong and
      positive (respective mean scores of 4.8 and 4.7 on a scale ranging from 1 to 5).
      Mean overall urinary Qualiveen QOL score was 0.8 (0.09-2.67) indicating a low
      negative impact of urinary disability on QOL. In patients <45 years, 52.6% (n =
      10) reported a moderate to important improvement of their sexuality after
      surgery. Renal function remained stable during follow-up. CONCLUSION: In the long
      term, continent cystostomy with bladder enlargement provides great satisfaction
      to almost most patients. It has a strong positive impact on general and specific
      urinary QOL, patients' autonomy and urinary continence. In young patients a
      positive impact on sexuality was also noticed. These encouraging data, that need
      to be confirmed, constitute interesting information to provide to neurologic
      patients to help them deciding whether they are willing to undergo continent
      cystostomy surgery.

PMID- 29464757
TI  - Pelvimetry in nulliparous and primiparous women using 3 Tesla magnetic resonance
      imaging.
AB  - AIMS: To perform pelvimetry in nulliparous and primiparous women using 3 Tesla
      magnetic resonance imaging (3T MRI). METHODS: Twenty-five nulliparous volunteers
      and 25 primiparous women underwent pelvic 3T MRI within one week after vaginal
      childbirth in a prospective clinical single-center trial. The pelvimetric
      parameters interspinous distance (ISD), intertuberous distance (ITD), sagittal
      outlet (SO), obstetric conjugate (OC), and coccygeal curved length (CCL) were
      adapted from anthropometric measurements as well as from sonographic and computed
      tomography-based pelvimetry performed on high-resolution T2-weighted images. We
      compared the results of the two study groups to one another, recent literature
      and postpartum-diagnosed levator ani muscle (LAM) injuries. RESULTS: The mean
      values for primipara/nullipara were ISD 107 +/- 8.3/105 +/- 8.4 mm, ITD 119.8 +/-
      10.2/118.4 +/- 13.1 mm, OC 129.4 +/- 10/130.8 +/- 6.9 mm, SO 114.3 +/- 7.8/112.5
      +/- 8.9 mm, and CCL 37.3 +/- 7.4/39 +/- 8 mm. Significant differences (P < 0.05)
      were found between the results for OC, SO, and CCL (primipara) and ISD, ITD and
      OC (nullipara) and the values in the literature. No significant difference in
      pelvimetric values was found between the groups. A significant correlation was
      found between the pelvimetric parameters and five types of LAM injuries.
      CONCLUSIONS: Two-dimensional 3T MRI combines high-resolution images with
      objective pelvimetric measurements applicable in a postpartum setting. Our
      results provide a good foundation for further MRI-based studies evaluating the
      bony pelvis and its relation to LAM injuries during vaginal childbirth.

PMID- 29464758
TI  - A genomic and clinicopathological study of non-small-cell lung cancers with
      discordant ROS1 gene status by fluorescence in-situ hybridisation and
      immunohistochemical analysis.
AB  - AIMS: ROS1 immunohistochemistry (IHC) using D4D6 antibody is a useful tool for
      screening patients with non-small-cell lung cancer (NSCLC) who may be suitable
      for targeted therapy. Many studies and our data have identified cases that
      express the ROS1 protein strongly but are negative for ROS1 by fluorescence in
      situ hybridisation (FISH). The present study investigated the driver mutation and
      clinicopathological characteristics of 26 discordant cases (ROS1 IHC-positive but
      FISH-negative) to find new clues for distinguishing real ROS1-rearranged cases.
      METHODS AND RESULTS: Tumours from 26 discordant cases were analysed for
      clinicopathological characteristics, mutations in EGFR, KRAS, ERBB2, BRAF and
      PIK3CA; fusions in ALK and RET; and amplifications in MET, ERBB2 and ROS1. ROS1
      rearranged NSCLCs were significantly more likely to be found in younger patients
      and at an advanced stage; they showed cribriform features, extracellular mucus
      and psammoma bodies, whereas ROS1-discordant cases were found in older patients
      at a relatively early tumour-node-metastasis (TNM) stage and showed a lepidic
      growth pattern (all P < 0.001). Most ROS1-rearranged NSCLCs had no concurrent
      mutation, whereas 73% of discordant cases harboured genetic aberrations,
      including EGFR and ERBB2. Compared with general lung adenocarcinomas, ERBB-2
      abnormality was disproportionately high in ROS1-discordant cases. Moreover, we
      optimised the scoring criteria for ROS1 IHC as 'H score > 150 and no concurrent
      mutations'; the specificity was then increased to 81.6%. CONCLUSIONS: Compared
      with ROS1-rearranged cases, ROS1-discordant patients showed distinct clinical and
      morphological features and often harboured another oncogenic driver alteration.
      The use of optimised screening criteria will increase the specificity of ROS1
      antibody.

PMID- 29464760
TI  - Desmoplastic transformation of a nodular melanoma arising from a speckled
      lentiginous nevus.

PMID- 29464759
TI  - Urine: Waste product or biologically active tissue?
AB  - AIMS: Historically, urine has been viewed primarily as a waste product with
      little biological role in the overall health of an individual. Increasingly, data
      suggest that urine plays a role in human health beyond waste excretion. For
      example, urine might act as an irritant and contribute to symptoms through
      interaction with-and potential compromise of-the urothelium. METHODS: To explore
      the concept that urine may be a vehicle for agents with potential or occult
      bioactivity and to discuss existing evidence and novel research questions that
      may yield insight into such a role, the National Institute of Diabetes and
      Digestive and Kidney Disease invited experts in the fields of comparative
      evolutionary physiology, basic science, nephrology, urology, pediatrics,
      metabolomics, and proteomics (among others) to a Urinology Think Tank meeting on
      February 9, 2015. RESULTS: This report reflects ideas that evolved from this
      meeting and current literature, including the concept of urine quality, the
      biological, chemical, and physical characteristics of urine, including the
      microbiota, cells, exosomes, pH, metabolites, proteins, and specific gravity
      (among others). Additionally, the manuscript presents speculative, and hopefully
      testable, ideas about the functional roles of urine constituents in health and
      disease. CONCLUSION: Moving forward, there are several questions that need
      further understanding and pursuit. There were suggestions to consider actively
      using various animal models and their biological specimens to elaborate on basic
      mechanistic information regarding human bladder dysfunction.

PMID- 29464761
TI  - Evolution of facial innervation in anomodont therapsids (Synapsida): Insights
      from X-ray computerized microtomography.
AB  - Anomodontia was the most successful herbivorous clade of the mammalian stem
      lineage (non-mammalian synapsids) during the late Permian and Early Triassic.
      Among anomodonts, Dicynodontia stands apart because of the presence of an osseous
      beak that shows evidence of the insertion of a cornified sheath, the ramphotheca.
      In this study, fourteen anomodont specimens were microCT-scanned and their
      trigeminal canals reconstructed digitally to understand the origin and evolution
      of trigeminal nerve innervation of the ramphotheca. We show that the pattern of
      innervation of the anomodont "beak" is more similar to that in chelonians (the
      nasopalatine branch is enlarged and innervates the premaxillary part of the
      ramphotheca) than in birds (where the nasopalatine and maxillary branches play
      minor roles). The nasopalatine branch is noticeably enlarged in the beak-less
      basal anomodont Patranomodon, suggesting that this could be an anomodont or
      chainosaur synapomorphy. Our analyses suggest that the presence or absence of
      tusks and postcanine teeth are often accompanied by corresponding variations of
      the rami innervating the caniniform process and the alveolar region,
      respectively. The degree of ossification of the canal for the nasal ramus of the
      ophthalmic branch also appears to correlate with the presence of a nasal boss.
      The nasopalatine canal is absent from the premaxilla in the Bidentalia as they
      uniquely show a large plexus formed by the internal nasal branch of the maxillary
      canal instead. The elongated shape of this plexus in Lystrosaurus supports the
      hypothesis that the rostrum evolved as an elongation of the subnarial region of
      the snout. Finally, the atrophied and variable aspect of the trigeminal canals in
      Myosaurus supports the hypothesis that this genus had a reduced upper
      ramphotheca.

PMID- 29464762
TI  - KPR-2579, a novel TRPM8 antagonist, inhibits acetic acid-induced bladder afferent
      hyperactivity in rats.
AB  - AIMS: Transient receptor potential melastatin 8 (TRPM8) is proposed to be a
      promising therapeutic target for hypersensitive bladder disorders. We examined
      the effects of KPR-2579, a novel selective TRPM8 antagonist, on body temperature
      and on mechanosensitive bladder single-unit afferent activities (SAAs) provoked
      by intravesical acetic acid (AA) instillation in rats. METHODS: Female Sprague
      Dawley rats were used. Effects of cumulative intravenous (i.v.) administrations
      of KPR-2579 (0.03-1 mg/kg) on deep body temperature were investigated (N = 18).
      In separate animals, effects of bolus administration of KPR-2579 (0.03 or 0.3
      mg/kg, i.v.) on bladder hyperactivity induced by intravesical instillation of
      0.1% AA were investigated using cystometry (N = 57) in a conscious free-moving
      condition or urethane-anesthetized condition, and SAA measurements (N = 41) were
      performed in a urethane-anesthetized condition. RESULTS: KPR-2579 at any doses
      tested did not affect body temperature. In cystometry measurements, a high dose
      (0.3 mg/kg) of KPR-2579 counteracted the shortened intercontraction interval
      provoked by AA instillation. In SAA measurements, 48 single afferent fibers (n =
      24 in each fiber) were isolated. AA instillations significantly increased the
      SAAs of C fibers, but not of Adelta fibers, in the presence of KPR-2579's vehicle
      and a low dose (0.03 mg/kg) of KPR-2579. Pretreatment with a high dose (0.3
      mg/kg) of KPR-2579 significantly inhibited the AA-induced activation of C-fiber
      SAAs. CONCLUSION: The present results suggest that TRPM8 channels play a role in
      the AA-induced pathological activation of mechanosensitive bladder C fibers in
      rats. KRP-2579 may be a promising drug for hypersensitive bladder disorders.

PMID- 29464763
TI  - Promising therapeutic option for cutaneous plasmacytosis: 308-nm excimer lamp.

PMID- 29464764
TI  - A pilot feasibility study of treating overactive bladder patients with
      percutaneous saphenous nerve stimulation.
AB  - AIMS: Effective long-term treatment of overactive bladder (OAB) remains a
      significant clinical challenge. We present our initial experience with a new
      bladder neuromodulation method that electrically targets the saphenous nerve
      (SAFN). METHODS: A total of 18 OAB patients (female, 55-84 years) were provided
      with percutaneous SAFN stimulation. The SAFN was targeted with a needle electrode
      inserted below the medial condyle of the tibia. Activation of the SAFN was
      confirmed by the patient's perception of paresthesia radiating down the leg.
      Electrical stimulation was applied for 30 min and subsequently repeated weekly
      for 3 months. The effects of stimulation were assessed by a 4-day bladder diary
      and quality-of-life questionaire (OAB-q). RESULTS: Percutaneous SAFN stimulation
      was confirmed in all 16 patients who completed the study, and no adverse events
      were reported. Positive response to SAFN stimulation was achieved in 87.5% (14 of
      16) of patients, as determined by either a minimum 50% reduction in bladder
      symptoms or a minimum 10 point increase in the HRQL total score. CONCLUSIONS:
      Electrical activation of the SAFN was consistently achieved using anatomical
      landmarks and patient feedback. The procedure was well tolerated and, based on
      our small cohort of patients, appears efficacious, and safe. This pilot study
      provides early feasibility data that points to a promising new intervention for
      treating OAB.

PMID- 29464765
TI  - Delay of alternative antiviral therapy and poor outcomes of acyclovir-resistant
      herpes simplex virus infections in recipients of allogeneic stem cell transplant 
      a retrospective study.
AB  - Acyclovir is commonly used to prevent and treat herpes simplex virus (HSV)
      reactivation after hematopoietic cell transplant (HCT), and only few reports have
      been published on acyclovir-resistant HSV in HCT recipients. We reviewed the
      medical records of patients with a microbiologic diagnosis of acyclovir-resistant
      HSV by plaque reduction test who received an HCT from 2002 through 2014. A total
      of 4 028 HCTs were performed during the study period, and 18 of the recipients
      met the diagnostic criteria for acyclovir-resistant HSV. All cases had undergone
      allogeneic HCTs. Most patients were in the pre-engraftment period or on systemic
      corticosteroid therapy for graft-versus-host disease (GVHD). The median time
      between diagnosis and susceptibility testing was 15 days, and antiviral therapy
      was changed at a median of 27 days. Patients required prolonged therapy (~80
      days), and many had serious complications including renal failure and
      hospitalization. In conclusion, acyclovir-resistant HSV infection is more likely
      during the period of profound deficit in T-cell-mediated immunity and is
      associated with significant morbidities. Higher doses of acyclovir prophylaxis
      might be needed for patients with history of HSV during pre-engraftment or GVHD
      treatment. In patients who do not respond or progress after 1 week of acyclovir
      therapy, testing for drug-resistant HSV, and early switch to an alternative
      antiviral should be considered.

PMID- 29464767
TI  - Afterword: materialities, care, 'ordinary affects', power and politics.
AB  - In this paper I explore how the papers in this volume offer ways of thinking
      about materialities of care in terms of political ecologies, including
      hierarchies of value as well as assemblages, in which strategic agendas are made
      present in everyday practices, with profound and ordinary affects, as well as
      effects. I show how power can work through the association of multiple and
      heterogeneous materials and social processes to create 'thresholds', as spaces
      through which people must pass in order to be included as patients, and which
      circulate specific imaginaries over what counts as an appropriate need. I go on
      to suggest how some material practices are made mundane and immaterial, that is
      inconsequential, so that by drawing attention to their importance in how care is
      done (or not done) the papers help disrupt the commonplace production and
      reproduction of the 'neglected things' (Puig de la Bellacasa ) of healthcare
      environments, and by so doing help reimagine what is important for occasions to
      actually be caring. I then shift to thinking about a sensibility, one that is
      highly valued in this collection of articles, that helps illuminate different
      imaginaries of care to those that dominate healthcare environments, an approach
      that I have called elsewhere 'relational extension', and in the example I offer
      here show how shifts in extension as a form of motility disrupts stabilities and
      their reproduction, to accomplish different forms of world-making.

PMID- 29464768
TI  - Dressing disrupted: negotiating care through the materiality of dress in the
      context of dementia.
AB  - This paper explores how the materiality of dress mediates and shapes practices of
      care in the context of dementia. Earlier research called for an approach to
      conceptualising care that recognised the role played by everyday artefacts. We
      extend this to a consideration of dress and dressing the body in relation to
      people with dementia that involves the direct manipulation of material objects,
      as well as the materiality of bodies. The paper draws on an ESRC funded study
      Dementia and Dress, which examined experiences of dress for people with dementia,
      families and care-workers using ethnographic and qualitative methods. Our
      analysis explores the process of dressing the body, the physicality of guiding
      and manipulating bodies into clothing, dealing with fabrics and bodies which 'act
      back' and are resistant to the process of dressing. We consider how the
      materiality of clothing can constrain or enable practices of care, exploring
      tensions between garments that support ease of dressing and those that sustain
      identity. Examining negotiations around dress also reveals tensions between
      competing 'logics' of care (Mol ).

PMID- 29464769
TI  - Becoming at home in residential care for older people: a material culture
      perspective.
AB  - Residential homes encourage new residents to bring belongings with them, so that
      they can personalise their room and 'feel at home'. Existing literature on
      material culture in residential homes views objects as symbols and repositories
      of home and identity, which can facilitate a sense of belonging in residents
      through their display in residents' rooms. I suggest that this both
      misunderstands the processual and fluid nature of home and identity, and
      conceptualises objects as essentially passive. This article uses ethnographic
      data and theories of practice and relationality to argue that rather than the
      meaning of home being inherent in objects, or felt subjectively by residents,
      meaning is generated through ongoing, everyday interactions between the two. I
      show that residents became at home by acquiring new things -as well as displaying
      existing possessions - and also through interacting with mundane objects in
      everyday social and relational practices such as cleaning and hosting. I conclude
      that being at home in older people's residential homes need not be so different
      from being at home at other stages of the life course and in other settings. This
      challenges conceptualisations of older people's homes - and older age itself - as
      somehow unknowable and unfamiliar.

PMID- 29464766
TI  - Systemic and transdermal melatonin administration prevents neuropathology in
      response to perinatal asphyxia in newborn lambs.
AB  - Perinatal asphyxia remains a principal cause of infant mortality and long-term
      neurological morbidity, particularly in low-resource countries. No
      neuroprotective interventions are currently available. Melatonin (MLT), a potent
      antioxidant, anti-inflammatory and antiapoptotic agent, offers promise as an
      intravenous (IV) or transdermal therapy to protect the brain. We aimed to
      determine the effect of melatonin (IV or transdermal patch) on neuropathology in
      a lamb model of perinatal asphyxia. Asphyxia was induced in newborn lambs via
      umbilical cord occlusion at birth. Animals were randomly allocated to melatonin
      commencing 30 minutes after birth (60 mg in 24 hours; IV or transdermal patch).
      Brain magnetic resonance spectroscopy (MRS) was undertaken at 12 and 72 hours.
      Animals (control n = 9; control+MLT n = 6; asphyxia n = 16; asphyxia+MLT [IV n =
      14; patch n = 4]) were euthanised at 72 hours, and cerebrospinal fluid (CSF) and
      brains were collected for analysis. Asphyxia resulted in severe acidosis (pH 6.9
      +/- 0.0; lactate 9 +/- 2 mmol/L) and altered determinants of encephalopathy. MRS
      lactate:N-acetyl aspartate ratio was 2.5-fold higher in asphyxia lambs compared
      with controls at 12 hours and 3-fold higher at 72 hours (P < .05). Melatonin
      prevented this rise (3.5-fold reduced vs asphyxia; P = .02). Asphyxia
      significantly increased brain white and grey matter apoptotic cell death
      (activated caspase-3), lipid peroxidation (4HNE) and neuroinflammation (IBA-1).
      These changes were significantly mitigated by both IV and patch melatonin.
      Systemic or transdermal neonatal melatonin administration significantly reduces
      the neuropathology and encephalopathy signs associated with perinatal asphyxia. A
      simple melatonin patch, administered soon after birth, may improve outcome in
      infants affected by asphyxia, especially in low-resource settings.

PMID- 29464770
TI  - Placing care: embodying architecture in hospital clinics for immigrant and
      refugee patients.
AB  - This article is part of a hospital ethnography that investigates healthcare
      architecture as an aspect of an increasingly large, complex, and urgent global
      health issue: caring for refugees and other immigrants. It argues that hospitals
      are nodes in transnational social networks of immigrant and refugee patients that
      form assemblages of human and non-human objects. These assemblages co-produce
      place-specific hospital care in different hospital spaces. Place-specific
      tensions and power dynamics arise when refugees and immigrants come into contact
      with these biomedical spaces. The argument is developed by analysing waiting
      rooms and exam rooms in two outpatient clinics in one US hospital. The article
      draws its analysis from 9 months of fieldwork in 2012 that included following 69
      adult immigrant and refugee patients and observing their encounters with
      interpreters and clinic staff. Its inclusion of a transnational dimension for
      understanding place-specific hospital care adds conceptual and empirical depth to
      the study of how place matters in 21st century hospitals.

PMID- 29464771
TI  - Materialities of mundane care and the art of holding one's own.
AB  - The focus of this special issue is on how everyday or mundane materialities
      actively mediate health and care practices. This article extends this concern
      with the mundane to care itself and explores how specific materialities, such as
      shared spaces and everyday objects, not only mediate mundane care but enable it
      to happen. Our focus is on mundane help in the context of ill health, between
      people who are not immediate family, such as neighbours, acquaintances and others
      with whom we interact in our daily lives. Drawing on recent empirical studies of
      low-level support in two different parts of the UK, we show how the materialities
      of care can mediate the affective risks associated with receiving such help.
      Specifically, we investigate how materialities help people to balance the
      expression of their vulnerability with a need to retain their dignity, a practice
      referred to as 'holding one's own'. In doing so, we argue that materialities are
      not just the conduits for care - what care passes through - or things that
      mediate care. We suggest instead that materialities are part of how relationships
      of mundane care are constituted and maintained.

PMID- 29464772
TI  - The art and nature of health: a study of therapeutic practice in museums.
AB  - Drawing on ethnographic fieldwork and interviews at a major metropolitan art
      museum and botanic garden, this article considers the practical accomplishment of
      American museums' 'health turn' by tracing how museum staff develop therapeutic
      programmes for visitors with disabilities. In doing so, it considers one of
      medical sociology's fundamental theoretical questions - how ideologies of health
      order social life - in an unconventional empirical setting. Acknowledging
      contemporary arguments for both the relative merits and unintended consequences
      of this policy trend, I focus instead on the particular institutional
      arrangements, professional norms, and material cultures of art and nature that
      shape museums' therapeutic work, so as to reveal its effects. Data reveals
      ideological similarities, but practical differences, between museological and
      medical understandings of wellness. Extending a 'medical sociology of practice'
      to new contexts ultimately foregrounds the contingencies, and diversity, of
      therapeutic mechanisms and meanings, thereby broadening sociological research on
      healing and healthism.

PMID- 29464773
TI  - Thinking with care infrastructures: people, devices and the home in home blood
      pressure monitoring.
AB  - The growing consumer market in health monitoring devices means that technologies
      that were once the preserve of the clinic are moving into spaces such as homes
      and workplaces. We consider how one such device, blood pressure monitors, comes
      to be integrated into everyday life. We pursue the concept of 'care
      infrastructure', drawing on recent scholarship in STS and medical sociology, to
      illuminate the work and range of people, things and spaces involved in self
      monitoring. Drawing on a UK study involving observations and interviews with 31
      people who have used a consumer blood pressure monitor, we apply the concept
      beyond chronic illness, to practices involving consumer devices - and develop a
      critical account of its value. We conclude that the care infrastructure concept
      is useful to highlight the socio-material arrangements involved in self
      monitoring, showing that even for ostensibly personal devices, monitoring may be
      a shared practice that expresses care for self and for others. The concept also
      helps draw attention to links between different objects and spaces that are
      integral to the practice, beyond the device alone. Care infrastructure draws
      attention to the material, but ensures that analytic attention engages with both
      material and social elements of practice and their connections.

PMID- 29464774
TI  - Family food practices: relationships, materiality and the everyday at the end of
      life.
AB  - This article draws on data from a research project that combined participant
      observation with in-depth interviews to explore family relationships and
      experiences of everyday life during life-threatening illness. In it I suggest
      that death has often been theorised in ways that make its 'mundane' practices
      less discernible. As a means to foreground the everyday, and to demonstrate its
      importance to the study of dying, this article explores the (re)negotiation of
      food and eating in families facing the end of life. Three themes that emerged
      from the study's broader focus on family life are discussed: 'food talk' and
      making sense of illness; food, family and identity; and food 'fights'. Together
      the findings illustrate the material, social and symbolic ways in which food acts
      relationally in the context of dying, extending conceptual work on materiality in
      death studies in novel directions. The article also contributes new empirical
      insights to a limited sociological literature on food, families and terminal
      illness, building on work that theorises the entanglements of materiality, food,
      bodies and care. The article concludes by highlighting the analytical value of
      everyday materialities such as food practices for future research on dying as a
      relational experience.

PMID- 29464775
TI  - Conceptualising 'materialities of care': making visible mundane material culture
      in health and social care contexts.
AB  - 'Materialities of care' is outlined as a heuristic device for making visible the
      mundane and often unnoticed aspects of material culture within health and social
      care contexts, and exploring interrelations between materials and care in
      practice. Three analytic strands inherent to the concept are delineated:
      spatialities of care, temporalities of care and practices of care. These
      interconnecting themes span the articles in this special issue. The articles
      explore material practice across a range of clinical and non-clinical spaces,
      including hospitals, hospices, care homes, museums, domestic spaces, and
      community spaces such as shops and tenement stairwells. The collection addresses
      fleeting moments of care, as well as choreographed routines that order bodies and
      materials. Throughout there is a focus on practice, and relations between
      materials and care as ongoing, emergent and processual. We conclude by reflecting
      on methodological approaches for examining 'materialities of care', and offer
      some thoughts as to how this analytic approach might be applied to future
      research within the sociology of health and illness.

PMID- 29464776
TI  - Private finance initiative hospital architecture: towards a political economy of
      the Royal Liverpool University Hospital.
AB  - Sociological analysis has done much to illuminate the architectural contexts in
      which social life takes place. Research on care environments suggests that the
      built environment should not be understood as a passive backdrop to healthcare,
      but rather that care is conditioned by the architecture in which it happens. This
      article argues for the importance of going beyond the hospital walls to include
      the politics that underwrite the design and construction of hospital buildings.
      The article assesses the case of the yet-to-be-realised Liverpool Royal
      University Hospital, and the private finance initiative (PFI) funding that
      underpins the scheme, which is suggested as a salient 'external' context for
      understanding architecture's role in the provision of healthcare of many kinds
      for many years to come. PFI has major implications for democratic accountability
      and local economy, as well as for the architecture of the hospital as a site of
      care. Critical studies can illuminate these paradoxically visible-but-opaque
      hospital spaces by going beyond that which is immediately empirically evident, so
      as to reveal the ways in which hospital architecture is conditioned by political
      and economic forces.

PMID- 29464777
TI  - Associations between fatigue, physical activity, and QoL in patients with
      myeloproliferative neoplasms.
AB  - BACKGROUND: Patients with Philadelphia chromosome-negative Myeloproliferative
      Neoplasms (MPNs) report fatigue as the most common symptom and contributing
      significantly to reduction in their quality of life (QoL). Targeted non
      pharmacological intervention to increase levels of physical activity is suggested
      as a fatigue-reducing and QoL-enhancing intervention in MPN patients. The
      interrelationship between physical activity, fatigue, and QoL has, to our
      knowledge, never been reported. METHODS: We analyzed data from 1807 MPN patients.
      The primary analysis included a multiple regression model allowing fatigue to
      mediate the relationship between physical activity and QoL. RESULTS: We herein
      report the first and the largest study of patients with MPNs, in whom we have
      investigated the interrelationship between fatigue, physical activity, and QoL.
      Sedentary patients were more likely to report fatigue compared to highly active
      patients. There was a negative association between fatigue and QoL, and there was
      a positive association between physical activity and QoL. There was no
      interaction between fatigue and physical activity in the association with QoL.
      CONCLUSION: We found positive associations between level of physical activity and
      QoL, independently of fatigue being present. More research is needed before
      physical activity can be introduced as a targeted intervention to reduce fatigue
      and increase QoL in the management of patients.

PMID- 29464779
TI  - p.Glu477Lys mutation in keratin 5 is not necessarily mortal in generalized severe
      epidermolysis bullosa simplex.

PMID- 29464778
TI  - Expression of 14-3-3 sigma and eta proteins is unrelated to survival in
      metastatic high-grade serous carcinoma.
AB  - The objective of this study was to analyze the expression and clinical role of 14
      3-3 family proteins in high-grade serous carcinoma (HGSC). Protein expression of
      14-3-3 sigma (14-3-3sigma) and 14-3-3 eta (14-3-3eta) by immunohistochemistry was
      studied in 298 HGSC specimens (249 peritoneal, 49 pleural) and was analyzed for
      association with clinicopathologic parameters, chemoresponse and survival. The 14
      3-3sigma protein was diffusely (>75% of cells) expressed in 100% of carcinomas in
      analysis of a pilot series and was therefore not further analyzed. The 14-3-3eta
      protein was expressed to a variable extent in 260/298 (87%) effusions. Higher 14
      3-3eta protein expression was significantly related to higher CA 125 levels at
      diagnosis (p = 0.004), but was unrelated to other clinicopathologic parameters,
      chemoresponse or survival. Analysis of the association between 14-3-3eta and
      previously studied proteins regulating mitosis showed positive association with
      class III beta-tubulin expression (p = 0.025). The present study documents
      frequent expression of 14-3-3sigma and 14-3-3eta in HGSC effusions, but does not
      support a role for these proteins as prognostic markers or predictors of
      chemotherapy response in metastatic HGSC.

PMID- 29464780
TI  - Reply to questions on "Serial two-year follow-up after lymphaticovenular
      anastomosis for the treatment of lymphedema".

PMID- 29464781
TI  - Physicochemical Stability and Sterility of Standard Parenteral Nutrition
      Solutions and Simulated Y-Site Admixtures for Neonates.
AB  - BACKGROUND: Parenteral nutrition (PN) is frequently needed in neonatal intensive
      care. The use of standard PN has emerged as an easy-to-prescribe approach that
      allows one to have on-site, ready-to-use PN. The aim of this study was to test
      the physicochemical stability and sterility of 2 specific PN solutions as well as
      simulate Y-site compatibility with lipid injectable emulsions (ILE). METHODS: Our
      study considered 2 standard ILE-free PN solutions according to neonatal weight.
      These solutions were prepared in duplicate and stored at 4 degrees C. The
      following physicochemical parameters were tested: visual alterations, turbidity,
      pH, osmolarity, and calcium concentration. Sterility was assessed by means of
      agar blood culture and glucose concentration determination. In addition, we
      assessed the stability of simulated Y-site admixtures. For each standard ILE-free
      PN solution, 2 3-in-1 PN admixtures were designed, considering extreme values of
      fluid requirements (50 and 150 ml/kg/d) and a fat supply of 2 g/kg/24 h. The
      physicochemical parameters tested were phase separation and fat mean droplet size
      distribution. RESULTS: No alterations were detected by visual inspection. Calcium
      concentrations, turbidity, pH, and osmolarity values remained stable in all the
      determinations. All agar blood cultures were negative and glucose concentration
      was constant over time. Physical stability of simulated Y-site admixtures was
      considered acceptable as mean droplet size distribution remained below 500 nm in
      all the emulsions. CONCLUSION: The 2 tested standard ILE-free PN solutions for
      neonates are physicochemically stable and sterile for 31 days under refrigeration
      (4 degrees C). These solutions are also stable in case of Y-site administration
      with ILE at the conditions tested.

PMID- 29464782
TI  - Does obestatin modulate the hypothalamic appetite-regulating network in
      peripubertal sheep?
AB  - The participation of peripheral peptides in the processes regulating the food
      intake (energy homeostasis) at the central nervous system level remains unclear.
      This study focuses on the role of obestatin in neuronal activity within the
      hypothalamic appetite-regulating network in ruminants. The animals (n = 28) were
      randomly divided into two groups. The sheep in the control group received
      intracerebroventricular infusions of the Ringer-Locke solution, and the sheep in
      obestatin group were infused with obestatin (diluted in the Ringer-Locke
      solution) at 25 MUg per 120 MUl/hr. The series of four 1-hr infusions on 3
      consecutive days were performed, and immediately after the experiment, the sheep
      were decapitated. Selected brain regions were fixed in situ for further
      immunohistochemical analysis, while the remaining ones were frozen for real-time
      RT-qPCR analysis. Obestatin infusion elicited changes in the neuropeptide Y (NPY)
      neuronal network in the hypothalamus. The results obtained show that exogenous
      obestatin evoked an increase in npy and agrpmRNA expression in the mediobasal
      hypothalamus (MBH), while the immunoreactivity for NPY was decreased in the
      arcuate and periventricular nuclei. The increase in cart and pomcmRNA expression
      in the MBH was also observed. Moreover, increased levels of gpr39 receptor and
      npy receptor 1 mRNA expression were evident in obestatin-infused sheep. Based on
      these results, it can be concluded that obestatin plays a role in the modulation
      of appetite-regulating network at the central level in sheep. The results
      obtained suggest that the underlying mechanism may involve the modification of
      the activity of NPY/AgRP and CART/alpha-MSH neurons in the arcuate nucleus.

PMID- 29464783
TI  - Synthetic mid-urethral sling complications: Evolution of presenting symptoms over
      time.
AB  - INTRODUCTION: To study the evolution of type of presenting symptoms after mid
      urethral sling (MUS) placement relative to the interval between placement and
      subsequent synthetic sling removal (SSR) for complication(s). METHODS: An IRB
      approved, prospectively maintained database of women who underwent SSR was
      retrospectively reviewed for demographics, interval between MUS placement and
      SSR, history of chronic pain syndromes and recurrent urinary tract infections
      (RUTI), anti-incontinence and prolapse repairs, and MUS-related symptoms at
      presentation, including storage dysfunction, voiding dysfunction, RUTI, vaginal
      pain, non-vaginal pain, mesh exposure, and urinary incontinence (UI). Comparisons
      were made between patient groups divided into 2 and 4-year intervals to test the
      hypothesis that there would be higher rates of mesh exposure, pain and/or
      dyspareunia earlier, but higher rates of RUTI and UI in later groups. RESULTS:
      Between 2005-2017, 278/435 women met study criteria. Overall, mean number of
      presenting symptoms per patient was 3.8 +/- 1.4 and increased significantly in
      relation to time since MUS placement (P < 0.01). There was a significant
      difference between number of patients presenting with RUTI (P = 0.01), vaginal
      pain (P = 0.03), and UI (P = 0.03) between the 2-year groups and a significant
      difference between number of patients presenting with RUTI (P < 0.01), non
      vaginal pain (P = 0.01) and vaginal pain (P = 0.05) between the 4-year groups.
      CONCLUSIONS: In our tertiary care center, women with MUS-related complications
      presented with multiple symptoms that increased in number over time, with a
      higher rate of pain complaints in earlier groups but a higher rate of RUTI and UI
      in later groups.

PMID- 29464784
TI  - Total nasal reconstruction with 3D custom made porous titanium prosthesis and
      free thoracodorsal artery perforator flap: A case report.
AB  - Total nasal reconstruction is a challenging surgical procedure which usually
      involves a free flap, forehead flap, and cartilage grafts. In certain failure
      situations where patients do not accept the idea of anaplastology, possibilities
      become very limited. We report the case of a patient who underwent several
      reconstruction steps with multiple failures including free and local flaps and
      cartilage harvests which showed recurrent episodes of necrosis and infection
      leading to melting and collapse of reconstructed structures. Furthermore, the
      patient did not want any anaplastological rehabilitation. We proposed to the
      patient an innovative method that consists to print a three-dimensional custom
      made porous titanium prosthesis, based on the original shape of his nose, to
      replace the cartilage support. This implant was first inserted in a thoracodorsal
      artery perforator flap for primary integration before the free transfer of the
      complete structure, two months later. The free transfer was successful without
      any complication. A stable reconstruction and satisfying result was obtained. The
      patient did not want additional surgical improvement 24 months post-operatively,
      and resumed his professional activities. The possibility of using three
      dimensional custom titanium prostheses to replace the bone and cartilage support
      seems to be an interesting alternative for patients in the failure situation of
      nasal reconstruction.

PMID- 29464785
TI  - Astrocytes sustain long-term productive HIV-1 infection without establishment of
      reactivable viral latency.
AB  - The "shock and kill" HIV-1 cure strategy proposes eradication of stable cellular
      reservoirs by clinical treatment with latency-reversing agents (LRAs). Although
      resting CD4+ T cells latently infected with HIV-1 constitute the main reservoir
      that is targeted by these approaches, their consequences on other reservoirs such
      as the central nervous system are still unknown and should be taken into
      consideration. We performed experiments aimed at defining the possible role of
      astrocytes in HIV-1 persistence in the brain and the effect of LRA treatments on
      this viral sanctuary. We first demonstrate that the diminished HIV-1 production
      in a proliferating astrocyte culture is due to a reduced proliferative capacity
      of virus-infected cells compared with uninfected astrocytes. In contrast,
      infection of non-proliferating astrocytes led to a robust HIV-1 infection that
      was sustained for over 60 days. To identify astrocytes latently infected with HIV
      1, we designed a new dual-color reporter virus called NL4.3 eGFP-IRES-Crimson
      that is fully infectious and encodes for all viral proteins. Although we detected
      a small fraction of astrocytes carrying silent HIV-1 proviruses, we did not
      observe any reactivation using various LRAs and even strong inducers such as
      tumor necrosis factor, thus suggesting that these proviruses were either not
      transcriptionally competent or in a state of deep latency. Our findings imply
      that astrocytes might not constitute a latent reservoir per se but that
      relentless virus production by this brain cell population could contribute to the
      neurological disorders seen in HIV-1-infected persons subjected to combination
      antiretroviral therapy.

PMID- 29464786
TI  - Polymer-free drug-eluting stents for coronary artery disease.
AB  - Polymer-free drug-eluting stents (PF-DES) were designed with the expectation of
      avoiding late restenosis and thrombosis related to the polymer used in
      traditional DES platforms. Furthermore, due to similarities with bare metal
      stents after drug elution, PF-DES has been considered as particularly suitable
      for patients at high bleeding risk. A variety of PF-DES platforms have been
      clinically tested. Despite their theoretical advantages, PF platforms showed
      comparable clinical outcomes with modern permanent- or biodegradable polymer
      based DES up to 5 years after implantation. Use of more biocompatible polymers on
      the modern DES platforms is one of the reasons therefore. Their improved safety
      profile allows already less intensive antithrombotic regimes after DES. Hence,
      nowadays PF-DES platforms can be considered as one of many DES options for
      percutaneous treatment of coronary artery disease.

PMID- 29464787
TI  - Skin microbiota and human 3D skin models.
AB  - Although the role of the microbiota in skin homeostasis is still emerging, there
      is growing evidence that an intact microbiota supports the skin barrier. The
      increasing number of research efforts that are trying to shed more light on the
      human skin-microbiota interaction requires the use of suitable experimental
      models. Three-dimensional (3D) skin equivalents have been established as a
      valuable tool in dermatological research because they contain a fully
      differentiated epidermal barrier that reflects the morphological and molecular
      characteristics of normal human epidermis. In this review, we provide an overview
      of current 3D skin models and illustrate the potential of 3D skin models to study
      the human skin-microbiota interplay.

PMID- 29464788
TI  - The impact of child welfare legislation on domestic violence-related homicide
      rates.
AB  - State-specific statutes providing legal consequences for perpetrating domestic
      violence in the presence of a child have been enacted across the United States
      between 1996 and 2012. This paper examines the impact of this child welfare
      legislation, using a difference-in-differences approach. We find a significant
      drop in domestic violence-related homicide rates, when considering a wide range
      of victim-offender relationships. However, this result does not hold for marital
      homicides, suggesting that for this subpopulation, the risk of reprisal and
      consequent reduction in reporting may be counterbalancing the hypothesized
      deterrent impacts of the legislation.

PMID- 29464789
TI  - Surgical outcomes of mitral valve replacement with concomitant mitral annular
      reconstruction.
AB  - BACKGROUND AND AIM OF THE STUDY: We evaluated the early and long-term outcomes of
      mitral annular reconstruction (MAR) with pericardium during mitral valve
      replacement (MVR), and analyzed the risk factors associated with post-operative
      mortality. METHODS: Between May 1997 and April 2013, 78 consecutive patients
      underwent MVR with MAR. The indications for MAR were treatment for annular
      infection in native valve endocarditis (n = 23, 29.5%) or prosthetic valve
      endocarditis (n = 26, 33.3%), reinforcement of damaged annulus resulting from a
      previous operation (n = 17, 21.8%), complete excision of extensive calcification
      (n = 9, 11.5%), and left ventricular or left atrial rupture (n = 3, 3.8%).
      Patients were classified into infective endocarditis (n = 49) and non
      endocarditis groups (n = 29). The mean follow-up period was 59.4 +/- 47.3 months.
      RESULTS: There were two operative deaths and 11 cases of late mortality in the
      endocarditis group and five cases in the non-endocarditis group. Late prosthetic
      valve endocarditis occurred in four patients. The overall survival rate at 1 and
      10 years was 94.8% and 65.1%, respectively. There was no statistical difference
      in the overall survival, freedom from reoperation, and freedom from endocarditis
      rates between the groups (P = 0.565, P = 0.635, and P = 0.449, respectively).
      Univariable and multivariable analyses revealed that pre-operative left
      ventricular dysfunction (ejection fraction <40%) was an independent predictor of
      overall mortality. CONCLUSIONS: The early and long-term results of MAR with
      pericardium during MVR are acceptable in both endocarditis and non-endocarditis
      patients.

PMID- 29464790
TI  - Constrained Chemical Dynamics of CO Dissociation/Hydrogenation on Rh Surfaces.
AB  - Among noble metal catalysts, rhodium (Rh) is unique in its ability to perform a
      one-step synthesis of ethanol from syngas. The first steps following the
      adsorption of syngas on Rh surfaces are assumed to be responsible for the
      conversion of CO and the selectivity effects between C1 , C2 , and oxygenated
      species. In the current work, constrained ab initio molecular dynamics are
      applied to investigate the kinetics of CO dissociation and hydrogenation over
      flat and stepped Rh surfaces. The obtained barriers for the Rh(111) surface are
      in good agreement with the literature data. On the stepped Rh(211) surface, a
      large site-dependent variation in barrier height is shown, with the upper terrace
      exhibiting behavior comparable to the Rh(111) surface, whereas the barriers over
      the lower terrace site are generally significantly lower. The rate constants are
      calculated using transition state theory for both surfaces, and are applied
      successfully in a microkinetic model, confirming the predicted impact on CO
      conversion and CH4 /C1 -oxygenate/C2 Hn selectivity. In addition to the high
      accuracy energetics and rate constants reported for CO dissociation/hydrogenation
      and the presentation of an updated microkinetic mechanism for Rh catalysts, the
      applicability of constrained molecular dynamics for reaction barrier calculation
      is confirmed, and sensitive pathways affecting the selectivity between
      formaldehyde/methanol over Rh catalysts are highlighted.

PMID- 29464792
TI  - Editorial.

PMID- 29464794
TI  - In consideration of cannabis.

PMID- 29464791
TI  - Comparing pharmacological treatments for cocaine dependence: Incorporation of
      methods for enhancing generalizability in meta-analytic studies.
AB  - OBJECTIVES: Few head-to-head comparisons of cocaine dependence medications exist,
      and combining data from different randomized controlled trials (RCTs) is fraught
      with methodological challenges including limited generalizability of the RCT
      findings. This study applied a novel meta-analytic approach to data of cocaine
      dependence medications. METHODS: Data from 4 placebo-controlled RCTs (Reserpine,
      Modafinil, Buspirone, and Ondansetron) were obtained from the National Institute
      of Drug Abuse Clinical Trials Network (n = 456). The RCT samples were weighted to
      resemble treatment-seeking patients (Treatment Episodes Data Set-Admissions) and
      individuals with cocaine dependence in general population (National Survey on
      Drug Use and Health). We synthesized the generalized outcomes with pairwise meta
      analysis using individual-level data and compared the generalized outcomes across
      the 4 RCTs with network meta-analysis using study-level data. RESULTS: Weighting
      the data by the National Survey on Drug Use and Health generalizability weight
      made the overall population effect on retention significantly larger than the RCT
      sample effect. However, there was no significant difference between the
      population effect and the RCT sample effect on abstinence. Weighting changed the
      ranking of the effectiveness across treatments. CONCLUSIONS: Applying
      generalizability weights to meta-analytic studies is feasible and potentially
      provides a useful tool in assessing comparative effectiveness of treatments for
      substance use disorders in target populations.

PMID- 29464795
TI  - Advances in the prenatal diagnosis of monogenic disorders.

PMID- 29464796
TI  - Drug-like dietary vanilloids induce anticancer activity through proliferation
      inhibition and regulation of bcl-related apoptotic proteins.
AB  - In this study, a series of 20 structurally similar vanilloids (Vn) were tested
      for their antiproliferative effects against 12 human cancer cells: human breast
      (MCF-7 and MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver
      (HepG2), colorectal (HT-29 and HCT116), nasopharyngeal (CNE-1 and HK-1), and
      leukemic (K562 and CEM-SS) cancer cells. Among all the tested vanilloids, Vn16 (6
      shogaol) exhibited the most potent cytotoxic effects against human colorectal
      cancer cells (HT-29). The apoptotic induction effects exhibited by Vn16 on HT-29
      cells were confirmed using dual staining fluorescence microscopy and enzyme
      linked immunosorbent assay. The effects of Vn16 on regulation of 43 apoptotic
      related markers were determined in HT-29. The results suggested that 8 apoptotic
      markers (caspase 8, BAD, BAX, second mitochondrial-derived activator, caspase 3,
      survivin, bcl-2, and cIAP-2) were either upregulated or downregulated. These
      results further support the chemopreventive properties of foods that contain
      vanilloids.

PMID- 29464797
TI  - Percutaneous closure of tricuspid paravalvular leak without contrast for a
      patient with renal insufficiency.

PMID- 29464798
TI  - Bioactive compounds from the African medicinal plant Cleistochlamys kirkii as
      resistance modifiers in bacteria.
AB  - Cleistochlamys kirkii (Benth) Oliv. (Annonaceae) is a medicinal plant
      traditionally used in Mozambique to treat infectious diseases. The aim of this
      study was to find resistance modifiers in C. kirkii for Gram-positive and Gram
      negative model bacterial strains. One of the most important resistance mechanisms
      in bacteria is the efflux pump-related multidrug resistance. Therefore,
      polycarpol (1), three C-benzylated flavanones (2-4), and acetylmelodorinol (5)
      were evaluated for their multidrug resistance-reverting activity on methicillin
      susceptible and methicillin-resistant Staphylococcus aureus and Escherichia coli
      AG100 and AG100 A strains overexpressing and lacking the AcrAB-TolC efflux pump
      system. The combined effects of antibiotics and compounds (2 and 4) were also
      assessed by using the checkerboard microdilution method in both S. aureus
      strains. The relative gene expression of the efflux pump genes was determined by
      real-time reverse transcriptase quantitative polymerase chain reaction. The
      inhibition of quorum sensing was also investigated. The combined effect of the
      antibiotics and compound 2 or 4 on the methicillin-sensitive S. aureus resulted
      in synergism. The most active compounds 2 and 4 increased the expression of the
      efflux pump genes. These results suggested that C. kirkii constituents could be
      effective adjuvants in the antibiotic treatment of infections.

PMID- 29464799
TI  - Antiproliferative activity and apoptosis induction by trijuganone C isolated from
      the root of Salvia miltiorrhiza Bunge (Danshen).
AB  - In this study, we found that the hexane fraction of Danshen, the dried root of
      Salvia miltiorrhiza (Lamiaceae), exerted antiproliferative effects on human
      leukemia cells. Phytochemical investigation of the hexane fraction achieved the
      isolation of the tanshinone diterpenes: dihydrotanshinone I (1), trijuganone C
      (2), trijuganone B (3), cryptotanshinone (4), tanshinone IIA (5), and tanshinone
      I (6). Compound 2 showed significant antiproliferative activities against human
      leukemia cells HL-60, Jurkat, and U937. The antiproliferative activities of 2
      against human cancer and normal cells indicated that 2 exhibited potent
      antiproliferative activities with IC50 values less than 10 MUM against HL-60 and
      Jurkat cells as well as on the colon cancer cells DLD-1, COLO 205, and Caco-2.
      Compound 2 induced chromatin condensation, DNA fragmentation, activation of
      caspase-3, -8, and -9, and the cleavage of poly (ADP-ribose) polymerase (PARP) in
      HL-60 cells. Moreover, 2 activated Bid and Bax, leading to the loss of
      mitochondrial membrane potential, and 2 induced the cytochrome c release from
      mitochondria into cytosol. In contrast, Bcl-2 and Bcl-xL were unaffected by 2.
      These results suggest that 2 exerts antiproliferative effects via apoptosis
      induction mediated by mitochondrial dysfunction and caspase activation. Compound
      2 may serve as a candidate of potential chemotherapeutic agent for human
      leukemia.

PMID- 29464800
TI  - Gender differences in retirement planning: A longitudinal study among Spanish
      Registered Nurses.
AB  - BACKGROUND: Consistent patterns of gender differences in retirement planning
      behaviours have been shown but little is known about these behaviours among
      nurses. AIMS: To analyse the antecedents of the behaviours to prepare for
      retirement in nurses older than 55 and to identify differences as a function of
      gender. METHODS: A two-wave longitudinal study with Spanish nurses (n = 132).
      RESULTS: Statistically significant gender differences were revealed.
      Specifically, paths from financial knowledge to public protection and self
      insurance as well as paths from goals clarity to public protection all differed
      by gender. CONCLUSIONS: Patterns of retirement planning differentiated by gender
      apparently continue to emerge. IMPLICATIONS FOR NURSING MANAGEMENT: The study
      adds evidence showing that female nurses continue to rely on public protection as
      a solid support for their retirement. Despite their greater awareness of the
      importance of health care and social relations, savings and finance are more
      neglected by female nurses. Intervention should be aimed at fostering financial
      literacy of the entire nursing population, but particularly, the access of women
      to this training. Secondly, given that the differences persist, advance planning
      of social actions to protect those who will be living alone and economically
      helpless in old age.

PMID- 29464802
TI  - Comparison of stratum corneum thickness between two proposed methods of
      calculation using Raman spectroscopic depth profiling of skin water content.
AB  - BACKGROUND/PURPOSE: The stratum corneum (SC) is the most important layer for the
      barrier function of skin, so investigation of the SC is very important in
      cosmetic and medical research. Here, we calculated the SC thickness using the
      depth profile of the skin's water concentration based on previously described
      methods, and then compared the results. METHODS: Seven Korean women in their 30s
      participated in this study. Raman spectroscopy was used to measure the in vivo
      depth profile of skin water concentration. A total of 21 areas were measured at
      forearm. Microsoft Excel 2007 was used to calculate SC thickness based on the
      slope and intersection methods. RESULTS: The slope method and the intersection
      method gave a forearm SC thickness calculated at 21.3 +/- 2.6 MUm and 17.6 +/-
      2.8 MUm, respectively. There was a significant difference between the two
      calculation methods but the two methods showed strong correlation of SC thickness
      results (r = .899). CONCLUSION: Although there was a difference in calculated SC
      thickness of about 20% between the two methods, these results reveal that the two
      SC thickness calculation methods using Raman spectroscopy were suitable for
      measuring SC thickness, a finding consistent with other published results.

PMID- 29464803
TI  - The International Alliance for Responsible Drinking's response to Petticrew et
      al.: 'How alcohol industry organisations mislead the public about alcohol and
      cancer'.

PMID- 29464801
TI  - Herbal medicine for depression and anxiety: A systematic review with assessment
      of potential psycho-oncologic relevance.
AB  - Anxiety and depression are prevalent among cancer patients, with significant
      negative impact. Many patients prefer herbs for symptom relief to conventional
      medications which have limited efficacy/side effects. We identified single-herb
      medicines that may warrant further study in cancer patients. Our search included
      PubMed, Allied and Complementary Medicine, Embase, and Cochrane databases,
      selecting only single-herb randomized controlled trials between 1996 and 2016 in
      any population for data extraction, excluding herbs with known potential for
      interactions with cancer treatments. One hundred articles involving 38 botanicals
      met our criteria. Among herbs most studied (>=6 randomized controlled trials
      each), lavender, passionflower, and saffron produced benefits comparable to
      standard anxiolytics and antidepressants. Black cohosh, chamomile, and
      chasteberry are also promising. Anxiety or depressive symptoms were measured in
      all studies, but not always as primary endpoints. Overall, 45% of studies
      reported positive findings with fewer adverse effects compared with conventional
      medications. Based on available data, black cohosh, chamomile, chasteberry,
      lavender, passionflower, and saffron appear useful in mitigating anxiety or
      depression with favorable risk-benefit profiles compared to standard treatments.
      These may benefit cancer patients by minimizing medication load and accompanying
      side effects. However, well-designed larger clinical trials are needed before
      these herbs can be recommended and to further assess their psycho-oncologic
      relevance.

PMID- 29464804
TI  - Policy-relevant behaviours predict heavier drinking and mediate the relationship
      with age, gender and education status: Analysis from the International Alcohol
      Control Study.
AB  - INTRODUCTION AND AIMS: To investigate behaviours related to four alcohol policy
      variables (policy-relevant behaviours) and demographic variables in relation to
      typical quantities of alcohol consumed on-premise in six International Alcohol
      Control study countries. DESIGN AND METHODS: General population surveys with
      drinkers using a comparable survey instrument and data analysed using path
      analysis in an overall model and for each country. MEASURES: typical quantities
      per occasion consumed on-premise; gender, age; years of education, prices paid,
      time of purchase, time to access alcohol and liking for alcohol advertisements.
      RESULTS: In the overall model younger people, males and those with fewer years of
      education consumed larger typical quantities. Overall lower prices paid, later
      time of purchase and liking for alcohol ads predicted consuming larger typical
      quantities; this was found in the high-income countries, less consistently in the
      high-middle-income countries and not in the low middle-income country. Three
      policy-relevant behaviours (prices paid, time of purchase, liking for alcohol
      ads) mediated the relationships between age, gender, education and consumption in
      high-income countries. DISCUSSION AND CONCLUSIONS: International Alcohol Control
      survey data showed a relationship between policy-relevant behaviours and typical
      quantities consumed and support the likely effect of policy change (trading
      hours, price and restrictions on marketing) on heavier drinking. The path
      analysis also revealed policy-relevant behaviours were significant mediating
      variables between the effect of age, gender and educational status on
      consumption. However, this relationship is clearest in high-income countries.
      Further research is required to understand better how circumstances in low-middle
      income countries impact effects of policies.

PMID- 29464805
TI  - Embryonic and early development of the Zagros tooth-carp, Aphanius vladykovi
      (Actinopterygii: Cyprinodontidae).
AB  - The embryonic and early larval development of laboratory reared Zagros tooth
      carp, Aphanius vladykovi Coad, 1988, are described and illustrated. Development
      and embryogenesis start with the external fertilization of sticky, transparent
      and spherical telolecithal/macrolecithal eggs with a mean diameter of 1.61+/-
      0.12 mm and it continues with meroblastic/radial cleavage, blastulation/blastula
      formation, epibolic cell migration during gastrulation and organogenesis
      resulting in a newly hatched larvae of 5.23 +/- 0.09 mm in length with attached
      yolk sac at about 164 hr (at 24 +/- 1 degrees C) after fertilization.

PMID- 29464807
TI  - Leadership practices of nurse managers for implementing evidence-based nursing in
      China.
AB  - AIM: To explore leadership of Chinese nurse managers in evidence-based nursing
      implementation. BACKGROUND: Despite much in the literature that highlights the
      significance of involving nurse managers, the qualitative nature of how their
      leadership practices influence the evidence implementation has not yet been fully
      explored. METHODS: A qualitative secondary data analysis was conducted on 15
      transcripts of interviews of nurse managers from a parent grounded theory study.
      The method for analysis employed the directed content analysis approach, using
      the framework of Kouzes & Posner's Five Practices of Exemplary Leadership(r)
      model. RESULTS: All the leadership practice categories of Five Practices of
      Exemplary Leadership(r) were observed in the data. Two additional categories
      "getting oneself prepared" and "keep it going" were also identified as important
      leadership practices of nurse managers to exhibit during evidence-based practice
      implementation. CONCLUSION: This study advances the leadership model by providing
      validation of existing exemplars and suggests two new practices with exemplars
      for a better understanding of the nurse managers' role during evidence
      implementation. IMPLICATIONS FOR NURSING MANAGEMENT: Strategies are proposed to
      recognise, value and prepare nurse managers' leadership practices during evidence
      implementation. Emphasis should also be put on cultivating and developing
      individual nurses' professional practice to sustain evidence-based practice.

PMID- 29464806
TI  - Histopathological and immunophenotypic features of ipilimumab-associated colitis
      compared to ulcerative colitis.
AB  - BACKGROUND: Use of the immune checkpoint inhibitor ipilimumab is sometimes
      complicated by ipilimumab-associated colitis (Ipi-AC), an immune-mediated colitis
      that mimics inflammatory bowel disease. OBJECTIVE: We sought to characterize the
      histopathologic and immunophenotypic features of Ipi-AC and to directly compare
      these features to ulcerative colitis (UC). METHODS: This is a retrospective
      cohort study of 22 patients with Ipi-AC, 12 patients with treatment-naive UC and
      five controls with diarrhoea but normal endoscopic findings.
      Immunohistopathologic features were described, and quantitative
      immunohistochemistry (IHC) was performed for CD4, CD8, CD20, CD138 and FOXP3.
      RESULTS: Endoscopic findings in both the Ipi-AC and UC groups included ulcerated,
      oedematous and erythematous mucosa. Involvement of the GI tract was more diffuse
      in Ipi-AC. As compared to UC, a smaller proportion of Ipi-AC biopsies had basal
      plasmacytosis (14% for Ipi-AC vs. 92% for UC, P < 0.0001) and crypt distortion
      (23% for Ipi-AC vs. 75% for UC, P = 0.003), whereas Ipi-AC biopsies had more
      apoptotic bodies in the left colon (17.6 +/- 15.3 for Ipi-AC vs. 8.2 +/- 4.2 for
      UC, P = 0.011). Cryptitis, ulcerations and crypt abscesses were common in both
      groups. Biopsy specimens from Ipi-AC had a lower density of CD20-positive
      lymphocytes than UC (275.8 +/- 253.3 cells mm-2 for Ipi-AC vs. 1173.3 +/- 1158.2
      cells mm-2 for UC, P = 0.022) but had a similar density of CD4, CD8, CD138 and
      FOXP3-positive cells. CONCLUSIONS: Ipi-AC is a distinct pathologic entity with
      notable clinical and histopathological differences compared to UC. These findings
      provide insights into the pathophysiology of immune-related adverse events (iAEs)
      from ipilimumab therapy.

PMID- 29464808
TI  - Cancer diagnosis in patients with heart failure: epidemiology, clinical
      implications and gaps in knowledge.
AB  - Cancer and heart failure (HF) are common medical conditions with a steadily
      rising prevalence in industrialized countries, particularly in the elderly, and
      they both potentially carry a poor prognosis. A new diagnosis of malignancy in
      subjects with pre-existing HF is not infrequent, and challenges HF specialists as
      well as oncologists with complex questions relating to both HF and cancer
      management. An increased incidence of cancer in patients with established HF has
      also been suggested. This review paper summarizes the epidemiology and the
      prognostic implications of cancer occurrence in HF, the impact of pre-existing HF
      on cancer treatment decisions and the impact of cancer on HF therapeutic options,
      while providing some practical suggestions regarding patient care and
      highlighting gaps in knowledge.

PMID- 29464809
TI  - Mapping and characterization of positive and negative BOLD responses to visual
      stimulation in multiple brain regions at 7T.
AB  - External stimuli and tasks often elicit negative BOLD responses in various brain
      regions, and growing experimental evidence supports that these phenomena are
      functionally meaningful. In this work, the high sensitivity available at 7T was
      explored to map and characterize both positive (PBRs) and negative BOLD responses
      (NBRs) to visual checkerboard stimulation, occurring in various brain regions
      within and beyond the visual cortex. Recently-proposed accelerated fMRI
      techniques were employed for data acquisition, and procedures for exclusion of
      large draining vein contributions, together with ICA-assisted denoising, were
      included in the analysis to improve response estimation. Besides the visual
      cortex, significant PBRs were found in the lateral geniculate nucleus and
      superior colliculus, as well as the pre-central sulcus; in these regions,
      response durations increased monotonically with stimulus duration, in tight
      covariation with the visual PBR duration. Significant NBRs were found in the
      visual cortex, auditory cortex, default-mode network (DMN) and superior parietal
      lobule; NBR durations also tended to increase with stimulus duration, but were
      significantly less sustained than the visual PBR, especially for the DMN and
      superior parietal lobule. Responses in visual and auditory cortex were further
      studied for checkerboard contrast dependence, and their amplitudes were found to
      increase monotonically with contrast, linearly correlated with the visual PBR
      amplitude. Overall, these findings suggest the presence of dynamic neuronal
      interactions across multiple brain regions, sensitive to stimulus intensity and
      duration, and demonstrate the richness of information obtainable when jointly
      mapping positive and negative BOLD responses at a whole-brain scale, with ultra
      high field fMRI.

PMID- 29464810
TI  - Prevalence and risk of sport types to stress urinary incontinence in sportswomen:
      A cross-sectional study.
AB  - OBJECTIVE: The objective of our study was to investigate the prevalence and risk
      of developing stress urinary incontinence (SUI) in each type of high-intensity
      sport, and the associated impact on quality of life in sportswomen. METHODS: This
      cross-sectional study was conducted between March and November 2016. The study
      included 278 sportswomen. The basic inclusion criteria were being nulliparous and
      engaging in high-intensity physical activity. The exclusion criteria were
      childbirth, surgical treatment of gynecological and urological illnesses and
      urinary tract infection. For evaluation were used: The International Physical
      Activity Questionnaire (IPAQ), The International Consultation on Incontinence
      Questionnaire Urinary Incontinence (ICIQ-UISF), the Overactive Bladder
      Questionnaire (OAB-q), the Urinary Incontinence Quality of Life Scale (I-QOL).
      RESULTS: The highest percentage of SUI was found in athletes (23.8%), followed by
      volleyball players (19.6%). We found that cumulative metabolic equivalent (MET)
      did not affect SUI, but the type of sport did. The risk of SUI was highest in
      volleyball sportswomen (odds ratio[OR] = 2.16,95% confidence interval[CI] = 0.96
      4.89, P < 0.05) and athletes (OR = 2.56,95%CI = 0.87-7.51, P = 0.08). As assessed
      by the I- QOL, SUI in people who participated in fitness and athletics (e.g.,
      basketball, volleyball and handball) had a negative impact on quality of life
      including behavior, psychosocial impacts and social embarrassment score.
      CONCLUSION: Volleyball players have a 116% chance of getting SUI compared to
      women who play other types of sports that were analyzed as part of this study.
      Healthcare professionals should inform the population of sportswomen with risk
      factors for SUI in order to implement preventive physiotherapy for strengthening
      pelvic floor muscles.

PMID- 29464811
TI  - Novel splice site mutation in the LIPH gene in a patient with autosomal recessive
      woolly hair/hypotrichosis: Case report and published work review.
AB  - Autosomal recessive woolly hair is a relatively rare hereditary hair disorder
      characterized by sparse, short, curly hair. This condition is known to be caused
      by mutations in the LIPH gene, LPAR6 gene or KRT25 gene. In the Japanese
      population, most patients with autosomal recessive woolly hair carry one of two
      founder mutations in the LIPH gene, c.736T>A (p.Cys246Ser) or c.742C>A
      (p.His248Asn). However, occasionally, individuals with this condition carry
      compound heterozygous mutations, typically one founder mutation and another
      mutation. In this study, we describe a patient with a compound heterozygous
      mutation in the LIPH gene at c.736T>A and c.1095-3C>G. The latter mutation
      created a novel splice site. This was the fourth splice site mutation to be
      described in the LIPH gene. Furthermore, we performed an in vitro transcription
      assay in cultured cells, and demonstrated that the c.1095-3C>G mutation led to a
      frame-shift, which created a premature termination codon at the protein level
      (p.Glu366Ilefs*7). Finally, we summarized the mutations previously reported for
      the LIPH gene. Our findings provide further clues as to the molecular basis of
      autosomal recessive woolly hair.

PMID- 29464812
TI  - The female continence mechanism measured by high resolution manometry: Urethral
      bulking versus midurethral sling.
AB  - AIMS: Traditional technology to characterize urethral pressure changes during
      dynamic conditions is limited by slow response times or artifact-inducing
      withdrawal maneuvers. The 8F high-resolution manometry (HRM) catheter (ManoScanTM
      ESO, Covidien) has advantages of fast response times and the ability to measure
      urethral pressures along the urethral length without withdrawal. Our objective
      was to determine static and dynamic maximum urethral closure pressures (MUCPs)
      and resting functional urethral length (FUL) in women using HRM before and after
      transurethral bulking and compare results to other women who underwent
      midurethral sling (MUS). METHODS: We recorded rest, cough, and strain MUCPs and
      FUL in 24 women before and after transurethral bulking with polydimethylsiloxane
      (Macroplastique(r)) using the HRM catheter and compared these changes to HRM
      values from 26 women who had the same measures before and after MUS. RESULTS: At
      rest, MUCPs increased minimally after both urethral bulking and MUS (3 vs 0.4 cm
      H2 O respectively, P = 0.4). Under dynamic conditions there were statistically
      insignificant small increases in MUCP and these increases were markedly less than
      after MUS (cough: 1.5 vs 63.8 cm H2 O, P < 0.001 and strain: 11.5 vs 57.7 cm H2
      O, P < 0.001). FUL increased by 0.5 cm after transurethral bulking (P = 0.003),
      and decreased by 0.25 cm after MUS placement (P = 0.012). CONCLUSIONS: The
      mechanism of continence after urethral bulking differs from MUS. While MUS
      increases dynamic MUCP, bulking may rely on increasing the length of the
      continence zone.

PMID- 29464813
TI  - The economic burden of overactive bladder (OAB) and its effects on the costs
      associated with other chronic, age-related comorbidities in the United States.
AB  - AIMS: The prevalence of OAB increases with age and is associated with several
      chronic comorbidities. However, the impact of OAB on the healthcare costs of
      patients with such comorbidities is not well-understood. This study aimed to
      quantify the impact of OAB on healthcare costs and assess the potential
      moderating effects of OAB on the costs of patients with chronic comorbidities.
      METHODS: Adults with evidence of OAB/OAB-related therapy between 1/1/2008
      12/31/2013 were identified from two large, administrative claims databases. Per
      patient-per-month (PPPM) expenditures for OAB cases were estimated and compared
      to those of propensity score-matched subjects without OAB. Costs were modeled
      using ordinary least squares regression including main effects and interactions
      of chronic depression, dementia, diabetes, hypertension, and osteoporosis with
      OAB. Values for the comparisons were calculated on the original dollar scale
      using smearing estimators. RESULTS: A total of 110 059 pairs of OAB cases and
      matched non-OAB controls were identified. The mean, multivariable-adjusted, PPPM
      all-cause costs of OAB cases from the model without interactions were $3003,
      compared to $1123 for matched controls (P < 0.0001). In the model assessing the
      interactions of chronic comorbidities with OAB, those OAB patients with comorbid
      depression, dementia, diabetes, hypertension, and osteoporosis incurred
      significantly higher costs than controls with these comorbidities. The
      synergistic effect of these interactions was estimated to be $95-$574 PPPM.
      CONCLUSIONS: Within this US-based population, the healthcare costs of OAB
      patients were more than 2.5 times those of similar patients without OAB.
      Additionally, patients with OAB and chronic, age-related comorbidities incurred
      higher healthcare costs than non-OAB controls with the same comorbidities.

PMID- 29464814
TI  - DRD2 promoter methylation and measures of alcohol reward: functional activation
      of reward circuits and clinical severity.
AB  - Studies have identified strong associations between D2 receptor binding potential
      and neural responses to rewarding stimuli and substance use. Thus, D2 receptor
      perturbations are central to theoretical models of the pathophysiology of
      substance dependence, and epigenetic changes may represent one of the fundamental
      molecular mechanisms impacting the effects of alcohol exposure on the brain. We
      hypothesized that epigenetic alterations in the promoter region of the dopamine
      D2 receptor (DRD2) gene would be associated with cue-elicited activation of
      neural reward regions, as well as severity of alcohol use behavior. The current
      study leveraged functional neuroimaging (fMRI) during an alcohol reward paradigm
      (n = 383) to test associations among DRD2 promoter methylation in peripheral
      tissue, signal change in the striatum during the presentation of alcohol cues,
      and severity of alcohol use disorder (AUD). Controlling for age, DRD2 promoter
      methylation was positively associated with responses to alcohol cues in the right
      accumbens (partial r = 0.144, P = 0.005), left putamen (partial r = 0.133, P =
      0.009), right putamen (partial r = 0.106, P = 0.039), left caudate (partial r =
      0.117, P = 0.022), and right caudate (partial r = 0.133, P = 0.009), suggesting
      that DRD2 methylation was positively associated with robust activation in the
      striatum in response to reward cues. DRD2 methylation was also positively
      associated with clinical metrics of AUD severity. Specifically, controlling for
      age, DRD2 methylation was associated with Alcohol Use Disorders Identification
      Test total (partial r = 0.140, P = 0.002); Impaired Control Scale total (partial
      r = 0.097, P = 0.044) and Alcohol Dependence Scale total (partial r = 0.152, P =
      0.001). Thus, DRD2 methylation may be a critical mechanism linking D2 receptors
      with functional striatal brain changes and clinical severity among alcohol users.

PMID- 29464816
TI  - On the issue of choosing psychodiagnostic methods of measuring and scoring of
      cognitive deficit in case of schizophrenia.
AB  - RATIONALE, AIMS, AND OBJECTIVES: The article is dedicated to the search of more
      accurate psychodiagnostic methods and methods of evaluation that can help to
      define the degree of manifestation of cognitive deficiency among patients
      suffering from various schizophrenic disorders. The notions of cognitive
      deficiency and cognitive profile are analysed; we understand them as the
      correlation between intact and damaged components of cognitive processes and
      their diagrammatic representation. The authors prove that it is essential to
      provide a detailed scale of cognitive deficiencies detectable in case of
      schizophrenic disorders and to design universal algorithms that could translate
      the results of traditional content analysis of cognitive disorders into
      quantitative indicators. The article is based on the authors' experiments. We
      examined 128 patients, among whom 76 were suffering from paranoid schizophrenia
      (F20 according to ICD) and 52 were suffering from schizotypal disorder (F21
      according to ICD). METHOD: In evaluation of cognitive deficiency, we used both
      traditional methods devised in Russia and foreign tests that are seldom used by
      medical psychologists in their daily practice. We have analysed the difference in
      doing the cognitive tests between the groups of patients with different forms of
      schizophrenia and also suffering from it for different periods (up to 5 y and
      more than 5 y). RESULTS: On the basis of the quantitative indicators, a cognitive
      profile of each particular illness was compiled. As a result, we have defined
      different varieties of cognitive deficiency depending on the symptoms and
      dynamics of the disease. CONCLUSION: The authors have provided a detailed
      description of the structure and dynamics of the cognitive deficiency in case of
      different forms of schizophrenia and compiled cognitive profiles based on those
      data.

PMID- 29464815
TI  - Hepatic elastin content is predictive of adverse outcome in advanced fibrotic
      liver disease.
AB  - AIMS: The aim of this study was to determine if elastin content in needle core
      native liver biopsies was predictive of clinical outcome in patients with chronic
      hepatitis C virus-related chronic liver disease. METHODS AND RESULTS: Elastin
      contents in liver biopsies were determined by image analysis, technically
      validated in an independent centre, and correlated with outcome in patients with
      advanced (Ishak stage >=5) chronic hepatitis C virus-related chronic liver
      disease. Elastin was robustly quantified in an operator-independent and
      laboratory-independent manner, with very strong correlation of elastin staining
      measured with two methods of image classification (rs = 0.873, P < 0.00001).
      Elastin content (but not absolute scar content or Ishak stage) was predictive for
      future clinical outcomes. In a cohort of patients without sustained virological
      response, the median hepatic elastin content was 3.4%, and 17 patients (57%)
      progressed to a liver-related clinical outcome; 11 of the 15 patients (73%) with
      a hepatic elastin content of >3.4% progressed to a clinical outcome, as compared
      with only six of 15 (40%) with an elastin content of <3.4%. The difference in
      time to outcome was significant. CONCLUSIONS: We describe a simple and
      reproducible method for elastin quantification in liver biopsies that provides
      potentially valuable prognostic information to inform clinical management.

PMID- 29464817
TI  - The role of angiotensin receptor-neprilysin inhibitors in cardiovascular disease
      existing evidence, knowledge gaps, and future directions.
AB  - Although traditional renin-angiotensin system antagonists including angiotensin
      converting enzyme inhibitors and angiotensin receptor blockers have
      revolutionized the treatment of cardiovascular disease (CVD), the pivotal
      PARADIGM-HF trial demonstrated that sacubitril/valsartan, an angiotensin receptor
      neprilysin inhibitor (ARNI), was superior to an angiotensin-converting enzyme
      inhibitor in reducing cardiovascular morbidity and mortality in patients with
      heart failure and reduced ejection fraction. However, despite international
      regulatory approval and strong recommendations in the guidelines, uptake of
      sacubitril/valsartan has been disappointing. Sacubitril/valsartan is now the
      focus of a large programme of clinical trials testing the hypothesis that ARNIs
      may supplant conventional renin-angiotensin system inhibitors across the spectrum
      of CVD, including hypertension, secondary prevention after myocardial infarction,
      and heart failure with preserved ejection fraction. This review summarizes the
      existing evidence, knowledge gaps, and future directions of ARNIs in CVD based on
      discussions between clinical trialists, industry representatives, and regulatory
      authorities at the 2016 Global CardioVascular Clinical Trialists Forum in
      Washington, D.C.

PMID- 29464818
TI  - A Preview of Selected Articles - April 2018.

PMID- 29464820
TI  - Homelessness and Emergency Medicine: Furthering the Conversation.

PMID- 29464819
TI  - Mentalization and the left inferior frontal gyrus and insula.
AB  - OBJECTIVE: To determine if an interpersonal attribution bias associated with self
      perception, the externalizing bias, was related to neural activations during
      mentalization. METHODS: A functional magnetic resonance imaging task involving
      verbal appraisals measured neural activations when thinking about oneself and
      others in 59 adults, including healthy women as well as women with and recovered
      from anorexia nervosa. Whole-brain regressions correlated brain function during
      mentalization with the externalizing bias measured using the Internal, Personal,
      and Situational Attributions Questionnaire. RESULTS: Women with anorexia nervosa
      had a lower externalizing bias, demonstrating a tendency to self-attribute more
      negative than positive social interactions, unlike the other groups. The
      externalizing bias was correlated with activation of the left inferior frontal
      gyrus and posterior insula, when comparing thinking about others evaluating
      oneself with direct self-evaluation. DISCUSSION: Externalizing biases may provide
      an office-based assay reflecting neurocognitive disturbances in social self
      perception that are common during anorexia nervosa.

PMID- 29464821
TI  - Determination of adsorption and desorption of DNA molecules on freshwater and
      marine sediments.
AB  - AIMS: Free DNA and its adsorption by sediment in the aquatic environment lead to
      ambiguity in the identification of recent faecal pollution sources. The goal of
      this study was to understand the mechanisms of DNA adsorption and desorption on
      aquatic sediment under various conditions using quantitative polymerase chain
      reaction (qPCR). METHODS AND RESULTS: Both raw sewage (RS) DNA and purified PCR
      product (PPP) were used in adsorption and desorption experiments; autoclaved
      freshwater and marine sediments served as sorbents. Thirty-six hours were needed
      for adsorption to reach equilibrium. More DNA was adsorbed on both sediments in
      stream water than in 5 mmol l-1 NaCl and DNA adsorption increased in the presence
      of Ca2+ and Mg2+ . Successive desorption experiments showed that between 5% and
      22% of adsorbed DNA was desorbed. CONCLUSIONS: Organic matter and clay played a
      significant role in determining the DNA adsorption capacity on sediment. The data
      suggest the presence of multilayer adsorption. DNA molecules on sediments were
      mostly adsorbed through ligand binding rather than electrostatic binding.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Quantitative polymerase chain reaction
      assays provide a better way to investigate the DNA adsorption and desorption
      mechanisms by sediment. DNA desorption can potentially complicate the outcomes of
      microbial source tracking studies.

PMID- 29464823
TI  - Caudal articular process dysplasia of thoracic vertebrae in neurologically normal
      French bulldogs, English bulldogs, and Pugs: Prevalence and characteristics.
AB  - The aims of this study were to evaluate the prevalence and anatomical
      characteristics of thoracic caudal articular process dysplasia in French
      bulldogs, English bulldogs and Pugs presenting for problems unrelated to spinal
      disease. In this retrospective cross-sectional study, computed tomography scans
      of the thoracic vertebral column of these three breeds were reviewed for the
      presence and location of caudal articular process hypoplasia and aplasia, and
      compared between breeds. A total of 271 dogs met the inclusion criteria: 108
      French bulldogs, 63 English bulldogs, and 100 Pugs. A total of 70.4% of French
      bulldogs, 84.1% of English bulldogs, and 97.0% of Pugs showed evidence of caudal
      articular process dysplasia. Compared to French and English bulldogs, Pugs showed
      a significantly higher prevalence of caudal articular process aplasia, but also a
      lower prevalence of caudal articular process hypoplasia, a higher number of
      affected vertebrae per dog and demonstrated a generalized and bilateral spatial
      pattern more frequently. Furthermore, Pugs showed a significantly different
      anatomical distribution of caudal articular process dysplasia along the vertebral
      column, with a high prevalence of caudal articular process aplasia between T10
      and T13. This area was almost completely spared in French and English bulldogs.
      As previously suggested, caudal articular process dysplasia is a common finding
      in neurologically normal Pugs but this also seems to apply to French and English
      bulldogs. The predisposition of clinically relevant caudal articular process
      dysplasia in Pugs is possibly not only caused by the higher prevalence of caudal
      articular process dysplasia, but also by breed specific anatomical
      characteristics.

PMID- 29464824
TI  - Evaluation of electron tomography reconstruction methods for interface roughness
      measurement.
AB  - We evaluate the suitability of simultaneous iterative reconstruction technique
      (SIRT), filtered back projection, and simultaneous algebraic reconstruction
      technique methods for buried interface roughness measurements. We also
      investigate the effect of total electron dose distributed over the entire tilt
      series on measured roughness values. We investigate the applicability of the dose
      fractionation theorem by evaluating the effect of an increasing number of images,
      i.e., decreasing tilt increment size at fixed total electron irradiation dose on
      the quantitative measurement of buried interface roughness. The results indicate
      that SIRT is the most suitable method for reconstruction and a 3 degrees  to 5
      degrees  angle is optimal for the roughness measurement.

PMID- 29464825
TI  - Performance of pre-RT-qPCR treatments to discriminate infectious human
      rotaviruses and noroviruses from heat-inactivated viruses: applications of
      PMA/PMAxx, benzonase and RNase.
AB  - AIMS: Detection/Quantification of RNA viruses is mostly done by reverse
      transcriptase (RT)-(q)PCR, but it does not distinguish between infectious and
      noninfectious viruses. Our aim was to test, how different pretreatments before RT
      qPCR could eliminate positivity originated from external nucleic acids or genomes
      of damaged particles. METHODS AND RESULTS: Heat-inactivated (80 degrees C for 10
      min) rotavirus Wa strain and faecal samples containing rotavirus or norovirus
      were treated with PMA/PMAxx, benzonase or crude extract RNase prior to RT-qPCR.
      PMA/PMAxx pretreatments were not consistently efficient for RV, although they
      seemed to work to some extent for heat-inactivated norovirus. Benzonase and RNase
      provided consistently 2.2-2.8 log10 reductions in the titre of faecal rotavirus.
      CONCLUSIONS: All pretreatments need to be further validated for each virus
      separately, taking into account sample matrix and inactivation conditions.
      Although none of the pretreatments could completely render inactivated viruses
      undetectable, RNase worked most consistently for both rota- and norovirus.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study sheds light on capacity of the
      most common pre-RT-qPCR treatments to eliminate damaged, noninfectious
      rotaviruses and noroviruses after thermal treatment. To our knowledge, this is
      the first time, when benzonase has been used in this context.

PMID- 29464826
TI  - International Continence Society supported pelvic physiotherapy education
      guideline.
AB  - AIM: To provide a guideline of desired knowledge, clinical skills and education
      levels in Pelvic Physiotherapy (PT). Physiotherapy (PT) involves "using knowledge
      and skills unique to physiotherapists" and, "is the service only provided by, or
      under the direction and supervision of a physiotherapist."1 METHODS: The PT
      Committee, within the body of the International Continence Society (ICS),
      collected information regarding existing educational levels for pelvic floor PT.
      Through face to face and on on-line discussion consensus was reached which was
      summarized in three progressive educational levels based on knowledge and skills
      and brought together in a guideline. The guideline was submitted to all
      physiotherapists and the Educational Committee of the ICS, and after approval,
      submitted to the Executive Board of the ICS. RESULT: The guideline lists, in a
      progressive way, knowledge areas and skills to be achieved by education. It is
      broad and allows for individual interpretation based on local situations
      regarding education and healthcare possibilities. It is intended to be dynamic
      and updated on a regular basis. CONCLUSION: The proposed Pelvic PT education
      guideline is a dynamic document that allows course creators to plan topics for
      continuing course work and to recognize educational level of a therapist in the
      field of Pelvic PT. This education guideline can be used to set minimum worldwide
      standards resulting in higher skill levels for local pelvic physiotherapists and
      thereby better patient care outcome.

PMID- 29464827
TI  - Keep your feet warm? A cryptic refugium of trees linked to a geothermal spring in
      an ocean of glaciers.
AB  - Up to now, the most widely accepted idea of the periglacial environment is that
      of treeless ecosystems such as the arctic or the alpine tundra, also called the
      tabula rasa paradigm. However, several palaeoecological studies have recently
      challenged this idea, that is, treeless environments in periglacial areas where
      all organisms would have been exterminated near the glacier formed during the
      Last Glacial Maximum, notably in the Scandinavian mountains. In the Alps, the
      issue of glacial refugia of trees remains unanswered. Advances in glacier
      reconstructions show that ice domes did not cover all upper massifs, but glaciers
      filled valleys. Here, we used fossils of plant and malacofauna from a travertine
      formation located in a high mountain region to demonstrate that trees (Pinus,
      Betula) grew with grasses during the Lateglacial-Holocene transition, while the
      glacier fronts were 200-300 m lower. The geothermal travertine started to
      accumulate more than 14,500 years ago, but became progressively more meteogene
      about 11,500 years ago due to a change in groundwater circulation. With trees,
      land snails (gastropods) associated to woody or open habitats and aquatic mollusc
      were also present at the onset of the current interglacial, namely the Holocene.
      The geothermal spring, due to warm water and soil, probably favoured woody
      glacial ecosystems. This new finding of early tree growth, combined with other
      scattered proofs of the tree presence before 11,000 years ago in the western
      Alps, changes our view of the tree distribution in periglacial environments,
      supporting the notion of tree refugia on nunataks in an ocean of glaciers.
      Therefore, the tabula rasa paradigm must be revisited because it has important
      consequences on the global changes, including postglacial plant migrations and
      biogeochemical cycles.

PMID- 29464829
TI  - Clinical judgement in precision medicine.
AB  - Precision medicine, which aims to individualize care based upon the unique
      combination of genetic, environmental, and lifestyle features in particular
      patients, will require an evolution in clinical decision making. Practitioners of
      precision medicine will need to utilize an expanded body of medical knowledge
      derived from a wide variety of sources. Clinical judgement in the case-based
      reasoning necessary for individualizing care will involve understanding and
      utilizing methodological approaches not commonly invoked in medicine, including
      mechanistic and qualitative research results. Instead of searching for an answer
      in the published literature, precision medicine demands clinical judgement that
      finds the reasons for clinical decisions within, not without, the patient.

PMID- 29464828
TI  - Significance of tumor-infiltrating lymphocytes before and after neoadjuvant
      therapy for rectal cancer.
AB  - Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly
      common. However, biomarkers predicting the response to neoadjuvant therapy have
      not been established. Tumor-infiltrating lymphocytes (TILs) have a crucial effect
      on tumor progression and survival outcome as the primary host immune response,
      and an antitumor immune effect has been reported to contribute to the response to
      radiotherapy and chemotherapy. We investigated the significance of TILs before
      and after neoadjuvant treatment and the change in the density of those TILs.
      Sixty-four patients who underwent radical resection after neoadjuvant treatment
      for locally advanced rectal cancer were enrolled. The number of TIL subsets was
      examined using immunohistochemical staining of pretreatment biopsy samples and
      post-treatment resected specimens. In both the neoadjuvant chemotherapy cohort
      and the neoadjuvant chemoradiotherapy cohort, a low density of CD8+ TILs in
      pretreatment biopsy samples was associated with a poor response, and a low
      density of CD8+ TILs in post-treatment resected specimens was similarly
      associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the
      density of CD8+ TILs in post-treatment resected specimens was significantly
      increased compared with that in pretreatment biopsy samples. We concluded that T
      lymphocyte-mediated immune reactions play an important role in tumor response to
      neoadjuvant treatment for rectal cancer, and the evaluation of TILs in
      pretreatment biopsy samples might be a predictor of the clinical effectiveness of
      neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially
      chemoradiotherapy, could induce the activation of the local immune status.

PMID- 29464830
TI  - Dietary Approach to Stop Hypertension (DASH) diet and risk of renal function
      decline and all-cause mortality in renal transplant recipients.
AB  - Renal transplant recipients (RTR) are at risk of decline of graft function and
      premature mortality, with high blood pressure as an important risk factor for
      both. To study the association of the Dietary Approach to Stop Hypertension
      (DASH) diet with these adverse events, we conducted a prospective cohort study of
      adult RTR. Dietary data were collected using a validated 177-item food frequency
      questionnaire and an overall DASH-score was obtained. We included 632 stable RTR
      (mean +/- standard deviation age 53.0 +/- 12.7 years, 57% men). Mean DASH score
      was 23.8 +/- 4.7. During median follow-up of 5.3 (interquartile range, 4.1-6.0)
      years, 119 (18.8%) RTR had renal function decline, defined as a combined endpoint
      of doubling of serum creatinine and death-censored graft failure, and 128 (20.3%)
      died. In Cox-regression analyses, RTR in the highest tertile of the DASH score
      had lower risk of both renal function decline (hazard ratio [HR] = 0.57; 95%
      confidence interval [CI], 0.33-0.96, P = .03) and all-cause mortality (HR = 0.52;
      95%CI, 0.32-0.83, P = .006) compared to the lowest tertile, independent of
      potential confounders. Adherence to a DASH-style diet is associated with lower
      risk of both renal function decline and all-cause mortality. These results
      suggest that a healthful diet might benefit long-term outcome in RTR.

PMID- 29464831
TI  - Intensive remote monitoring versus conventional care in type 1 diabetes: A
      randomized controlled trial.
AB  - OBJECTIVE: While frequent contact with diabetes care providers may improve
      glycemic control among patients with type 1 diabetes (T1D), in-person visits are
      labor-intensive and costly. This study was conducted to assess the impact of an
      intensive remote therapy (IRT) intervention for pediatric patients with T1D.
      METHODS: Pediatric patients with T1D were randomized to IRT or conventional care
      (CC) for 6 months. Both cohorts continued routine quarterly clinic visits and
      uploaded device data; for the IRT cohort, data were reviewed and patients were
      contacted if regimen adjustments were indicated. Glycated hemoglobin (HbA1c)
      change from baseline was assessed at 6 and 9 months. Diabetes-related quality of
      life (QoL), healthcare services utilization, and hypoglycemic events were also
      tracked. RESULTS: Among 117 enrollees (60 IRT, 57 CC), mean (SD) 6-month %HbA1c
      change for IRT vs CC was -0.34 (0.85) (-3.7 mmol/mol) vs -0.05 (0.74) (-0.5
      mmol/mol) overall (P = .071); -0.15 (0.67) (1.6 mmol/mol) vs -0.02 (0.66) (0.2
      mmol/mol) for ages 8 to 12 (P = .541); and -0.50 (0.95) (-5.5 mmol/mol) vs -0.06
      (0.80) (-0.7 mmol/mol) for ages 13 to 17 (P = .056). Diabetes-related QoL
      increased by 6.5 and 1.3 points for IRT and CC, respectively (P = .062). Three
      months after intervention cessation, %HbA1c changed minimally among treated
      children aged 8 to 12 but increased by 0.22 (0.89) (2.4 mmol/mol) among those
      aged 13 to 17. CONCLUSIONS: IRT substantially affected diabetes metrics and
      improved QoL among pediatric patients with T1D. Adolescents experienced a
      stronger treatment effect, but had difficulty in sustaining improved control
      after intervention cessation.

PMID- 29464833
TI  - CgPDR1 gain-of-function mutations lead to azole-resistance and increased adhesion
      in clinical Candida glabrata strains.
AB  - Recently, Candida glabrata has emerged as a health-threatening pathogen and the
      rising resistance to antifungal agent in C. glabrata often leads to clinical
      treatment failure. To investigate the evolution of drug resistance and adherence
      ability in four paired clinical isolates collected before and after antifungal
      treatment. Sequence analysis, gene disruption, drug-susceptibility, adhesion
      tests and real-time quantitative PCR were performed. The azole-susceptible
      strains acquired azole resistance after antifungal therapy. Four gain-of-function
      (GOF) mutations in CgPDR1 were revealed by sequence analysis, namely G1099D,
      G346D, L344S and P927S, the last being reported for the first time. CDR1, CDR2
      and SNQ2 efflux pump gene expression levels were elevated in strains harbouring
      GOF mutations in CgPDR1, resulting in decreased azole susceptibility. CgPDR1
      alleles with distinct GOF mutations displayed different expression profiles for
      the drug-related genes. CgPDR1GOF mutations led to increased efflux pumps
      expression levels in a strain background independent way. Hyperactive Pdr1G1099D
      and Pdr1P927S displayed strain background-dependent increased adherence to host
      cells via upregulation of EPA1 transcription. Interestingly, the drug transporter
      gene expression levels did not always correspond with that of the adhesin EPA1
      gene. GOF mutations in CgPDR1 conferred drug resistance and increased adherence
      in the clinical strains, possibly endowing C. glabrata with increased viability
      and pathogenicity.

PMID- 29464834
TI  - Increasing incidence of HIV- associated tuberculosis in Romanian injecting drug
      users.
AB  - BACKGROUND: A high prevalence of tuberculosis (TB) among HIV-positive injecting
      drug users (IDUs) may fuel the TB epidemic in the general population of Romania.
      We determined the frequency and characteristics of TB in HIV-infected IDUs
      referred to a national centre. METHODS: Prospective observational cohort study of
      all newly-diagnosed HIV-positive IDUs admitted to Victor Babes Hospital,
      Bucharest, between January 2009 and December 2014. Socio-demographics, clinical
      characteristics and outcomes of HIV/TB co-infected IDUs were compared to HIV
      positive IDUs without TB. RESULTS: 170/598 (28.5%) HIV-infected IDUs were
      diagnosed with TB. The prevalence increased from 12.5% in 2009 to 32.1% in 2014
      (P < 0.001). HIV/TB co-infected individuals had lower median CD4 cell counts 75
      (vs. 450/mm3 , P < 0.0001) and higher median HIV viral loads 5.6 log10 (vs. 4.9
      log10 , P < 0.0001) when presenting to healthcare services. 103/170 (60.6%)
      HIV/TB co-infected IDUs were diagnosed with pulmonary TB. Resistant Mycobacterium
      tuberculosis strains were common, with 18/105 (17.1%) of patients having Multi
      Drug Resistant (MDR) disease. Higher mortality rate was associated with TB co
      infection (P < 0.0001), extra-pulmonary TB (P = 0.0026) and extensively drug
      resistant TB (P = 0.024). CONCLUSIONS: Tuberculosis (TB) is an increasing problem
      in HIV-infected IDUs in Romania. Presentation is often with advanced HIV,
      significant TB drug resistance and consequent outcomes are poor.

PMID- 29464832
TI  - Differential effects of donor-specific HLA antibodies in living versus deceased
      donor transplant.
AB  - The presence of donor-specific anti-HLA antibodies (DSAs) is associated with
      increased risk of graft failure after kidney transplant. We hypothesized that
      DSAs against HLA class I, class II, or both classes indicate a different risk for
      graft loss between deceased and living donor transplant. In this study, we
      investigated the impact of pretransplant DSAs, by using single antigen bead
      assays, on long-term graft survival in 3237 deceased and 1487 living donor kidney
      transplants with a negative complement-dependent crossmatch. In living donor
      transplants, we found a limited effect on graft survival of DSAs against class I
      or II antigens after transplant. Class I and II DSAs combined resulted in
      decreased 10-year graft survival (84% to 75%). In contrast, after deceased donor
      transplant, patients with class I or class II DSAs had a 10-year graft survival
      of 59% and 60%, respectively, both significantly lower than the survival for
      patients without DSAs (76%). The combination of class I and II DSAs resulted in a
      10-year survival of 54% in deceased donor transplants. In conclusion, class I and
      II DSAs are a clear risk factor for graft loss in deceased donor transplants,
      while in living donor transplants, class I and II DSAs seem to be associated with
      an increased risk for graft failure, but this could not be assessed due to their
      low prevalence.

PMID- 29464835
TI  - Perceived utility and relevance of intern well-being sessions.
AB  - BACKGROUND/AIM: We conducted a pilot project assessing the perceived utility and
      relevance of well-being sessions provided to interns at a large regional teaching
      hospital in Australia, with the aim of promoting intern well-being and fostering
      a nurturing and supportive learning and work hospital culture. METHODS: Our
      intervention involved two separate 60-min lectures covering well-being topics and
      skills to approximately 50 interns within protected teaching time, along with
      emailed well-being resources. Participants were emailed an online survey asking
      questions about value and novelty of the sessions, and work satisfaction and
      stress, as well as open comments. A request for an additional interview to
      explore responses in more depth was included. RESULTS: Fifty interns attended at
      least one of the sessions and 35 participated in the survey, six to an additional
      interview. Survey and interview data showed that the majority of interns
      perceived the sessions as valuable, relevant and useful and felt that ongoing
      sessions would benefit junior medical officers in future years. Feedback
      highlighted the importance of providing future sessions in person, incorporating
      an interactive approach and emphasised that work site factors and medical culture
      play a large causative role in their stress. CONCLUSIONS: We conclude that well
      being sessions are acceptable and useful to interns and should be incorporated
      into hospital teaching curricula, and evaluated. However, these programmes are
      unlikely to change the high stress experienced unless external and systemic
      stressors are addressed by all stakeholders.

PMID- 29464836
TI  - The presentation and management of platelet disorders in pregnancy.
AB  - Thrombocytopenia, defined as a platelet count less than 150 000 per microlitre,
      occurs in 7%-12% of all pregnancies. Apart from anaemia, it is the most common
      haematological disorder in pregnancy. Despite its frequent occurrence,
      thrombocytopenia often leads to difficulties of diagnosis and management in
      pregnancy. Typically, a pregnant woman will have platelet counts of 150 000 to
      450 000 per microlitre and platelet counts may be slightly lower than those of
      healthy, non-pregnant controls. Approximately, 8% of pregnant women will develop
      mild thrombocytopenia (100 000-150 000 per microlitre) and while 65% of these
      women will have no underlying pathology, all pregnant women with platelet counts
      of less than 100 000 per microlitre should undergo further clinical and
      laboratory assessment. Thrombocytopenia in pregnancy occurs as a result of
      multiple distinct conditions, we present four cases of thrombocytopenia in
      pregnancy encountered in our unit over a 12-month period. These include
      gestational thrombocytopenia, immune thrombocytopenic purpura (ITP), thrombotic
      thrombocytopenic purpura (TTP) and thrombocytopenia absent radius (TAR) syndrome.
      The literature review of these cases highlights the significance of
      identification, understanding pathophysiology and a multidisciplinary approach to
      these conditions. We refresh knowledge on these conditions and emphasise the
      importance of thrombocytopenia in pregnancy.

PMID- 29464837
TI  - Isolated vascular "v" lesions in liver allografts: How to approach this unusual
      finding.
AB  - According to the Banff criteria for kidney allografts, isolated vascular or "v"
      lesions are defined as intimal inflammation, age-inappropriate fibro-intimal
      hyperplasia, or both, without the presence of associated interstitial T cell
      mediated rejection (TCMR). In general, these lesions portend a worse outcome for
      kidney allografts, particularly in those where the "v" lesions are identified in
      patients with coexistent donor specific antibodies (DSA) or later after
      transplantation. Although affected arteries are rarely sampled in liver allograft
      biopsies, we identified nine patients at a mean of 1805 days posttransplantation
      and compared these to matched controls. Almost half (4 of 9) of the study patient
      biopsies showed inflammatory arteritis associated with focal or diffuse C4d
      positivity, which was not observed in matched controls. One "v" lesion patient
      progressed to rejection-related graft failure and two developed moderate/severe
      TCMR in subsequent biopsies, whereas only one rejection episode occurred in
      follow-up biopsies, and no rejection-related deaths or graft failures were
      detected in controls. In conclusion, patients with liver allograft isolated "v"
      lesions should undergo further evaluation and closer follow-up for impending TCMR
      and/or underlying co-existent chronic antibody-mediated rejection (AMR).

PMID- 29464838
TI  - Transformation/dissolution characterization of tungsten and tungsten compounds
      for aquatic hazard classification.
AB  - The transformation/dissolution protocol (T/DP) for metals and sparingly soluble
      metal compounds was applied to determine the transformation/dissolution (T/D)
      characteristics of yellow tungsten trioxide, WO3 ; blue tungsten oxide, WOx, x
      taken as 2.9; tungsten disulphide, WS2 ; tungsten metal, W; 3 samples of tungsten
      carbide, WC; sodium tungstate, Na2 WO4  . 2H2 O; ammonium paratungstate (APT),
      (NH4 )10 (H2 W12 O42 ) . 4H2 O; and ammonium metatungstate (AMT) (NH4 )6 (H2 W12
      O40 ) . 3H2 O. The T/D data were used to derive aquatic hazard classification
      outcomes under the United Nations Globally Harmonized System of Classification
      and Labelling of Chemicals (UN GHS) and European Union Classification, Labelling
      and Packaging of Substances and Mixtures (EU CLP) schemes by comparing the data
      with selected acute and chronic ecotoxicity reference values (ERVs) of 31 and
      3.37 mg W/L, respectively. In addition to the concentration of total dissolved
      tungsten (W), the T/D solutions were analyzed for the concentration of the
      tungstate anion, because speciation can be an important factor in establishing
      the ecotoxicity of dissolved metals. Results show that the tungstate anion was
      the predominant W-bearing species in solution for all substances examined at pH 6
      and 8.5. It was found that the 100 mg/L loadings of both the yellow WO3 and the
      blue WOx exceeded the 31 mg/L acute ERV, so they would classify as Acute 3
      Chronic 3 under the UN GHS scheme but they would not classify under the EU CLP.
      An effect of pH on the reactivity of the W metal was observed with 3% and 16% W
      dissolution at pH 6 and 8.5, respectively. Tungsten metal would not classify
      under either the UN GHS or EU CLP schemes nor would the WS2 . The WCs were the
      least reactive in terms of the 1% or less dissolution of the contained W at pH 6.
      A critical surface area for WC was calculated. The sodium tungstate, APT and the
      AMT all yielded, at pH 8.5, total dissolved W concentrations that would result in
      UN GHS Acute 3-Chronic 3 classifications. Integr Environ Assess Manag 2018;14:498
      508. (c) 2018 Her Majesty the Queen in Right of Canada. Integrated Environmental
      Assessment and Management (c) 2018 SETAC.

PMID- 29464839
TI  - Revealing the Active Species for Aerobic Alcohol Oxidation by Using Uniform
      Supported Palladium Catalysts.
AB  - The active species in supported metal catalysts are elusive to identify, and
      large quantities of inert species can cause significant waste. Herein, using a
      stoichiometrically precise synthetic method, we prepare atomically dispersed
      palladium-cerium oxide (Pd1 /CeO2 ) and hexapalladium cluster-cerium oxide (Pd6
      /CeO2 ), as confirmed by spherical-aberration-corrected transmission electron
      microscopy and X-ray absorption fine structure spectroscopy. For aerobic alcohol
      oxidation, Pd1 /CeO2 shows extremely high catalytic activity with a TOF of 6739 h
      1 and satisfactory selectivity (almost 100 % for benzaldehyde), while Pd6 /CeO2
      is inactive, indicating that the true active species are single Pd atoms.
      Theoretical simulations reveal that the bulkier Pd6 clusters hinder the
      interactions between hydroxy groups and the CeO2 surface, thus suppressing
      synergy of Pd-Ce perimeter.

PMID- 29464840
TI  - Distribution and density of melatonin receptors in human main pancreatic islet
      cell types.
AB  - Recent investigations of our group established that melatonin modulates hormone
      secretion of pancreatic islets via melatonin receptor types MT1 and MT2.
      Expression of MT1 and MT2 has been shown in mouse, rat, and human pancreatic
      islets as well as in the beta-, alpha-, and delta-cell lines INS-1, alphaTC1.9,
      and QGP-1. In view of these earlier investigations, this study was performed to
      analyze in detail the distribution and density of melatonin receptors on the main
      islet cell types in human pancreatic tissue obtained from nondiabetic and type 2
      diabetic patients. Immunohistochemical analysis established the presence of MT1
      and MT2 in beta-, alpha-, and delta-cells, but notably, with differences in
      receptor density. In general, the lowest MT1 and MT2 receptor density was
      measured in alpha-cells compared to the 2 other cell types. In type 2 diabetic
      islets, MT1 and MT2 receptor density was increased in delta-cells compared to
      normoglycemic controls. In human islets in batch culture of a nondiabetic donor,
      an increase of somatostatin secretion was observed under melatonin treatment
      while in islets of a type 2 diabetic donor, an inhibitory influence could be
      observed, especially in the presence of 5.5 mmol/L glucose. These data suggest
      the following: i) cell-type-specific density of MT1 and MT2 receptors in human
      pancreatic islets, which should be considered in context of the hormone secretion
      of islets, ii) the influence of diabetes on density of MT1 and MT2 as well as
      iii) the differential impact of melatonin on somatostatin secretion of
      nondiabetic and type 2 diabetic islets.

PMID- 29464841
TI  - Super-Chelators for Advanced Protein Labeling in Living Cells.
AB  - Live-cell labeling, super-resolution microscopy, single-molecule applications,
      protein localization, or chemically induced assembly are emerging approaches,
      which require specific and very small interaction pairs. The minimal disturbance
      of protein function is essential to derive unbiased insights into cellular
      processes. Herein, we define a new class of hexavalent N-nitrilotriacetic acid
      (hexaNTA) chelators, displaying the highest affinity and stability of all NTA
      based small interaction pairs described so far. Coupled to bright organic
      fluorophores with fine-tuned photophysical properties, the super-chelator probes
      were delivered into human cells by chemically gated nanopores. These super
      chelators permit kinetic profiling, multiplexed labeling of His6 - and His12 
      tagged proteins as well as single-molecule-based super-resolution imaging.

PMID- 29464842
TI  - The efficacy of botulinum neurotoxin A in the treatment of plaque psoriasis.

PMID- 29464843
TI  - Revisited analysis of a SHIVA01 trial cohort using functional mutational analyses
      successfully predicted treatment outcome.
AB  - It still remains to be demonstrated that using molecular profiling to guide
      therapy improves patient outcome in oncology. Classification of somatic variants
      is not straightforward, rendering treatment decisions based on variants with
      unknown significance (VUS) hard to implement. The oncogenic activity of VUS and
      mutations identified in 12 patients treated with molecularly targeted agents
      (MTAs) in the frame of SHIVA01 trial was assessed using Functional Annotation for
      Cancer Treatment (FACT). MTA response prediction was measured in vitro, blinded
      to the actual clinical trial results, and survival predictions according to FACT
      were correlated with the actual PFS of SHIVA01 patients. Patients with positive
      prediction had a median PFS of 5.8 months versus 1.7 months in patients with
      negative prediction (P < 0.05). Our results highlight the role of the functional
      interpretation of molecular profiles to predict MTA response.

PMID- 29464844
TI  - Dietary live yeast and increased water temperature influence the gut microbiota
      of rainbow trout.
AB  - AIMS: The objective was to determine the effects of dietary substitution of
      fishmeal (FM) with live yeast and increasing water temperature on the diversity
      and composition of gut microbiota in rainbow trout. METHODS AND RESULTS: Fish
      were fed either FM or yeast (Saccharomyces cerevisiae) and reared in water
      temperatures of either 11 degrees C (cold) or 18 degrees C (warm) for 6 weeks.
      Luminal content and mucosa were collected from the distal gut and the load,
      diversity and species abundance of yeast and bacteria were analysed using agar
      plating, MALDI-TOF and rRNA gene amplicon sequencing. Yeast in the gut of fish
      fed FM were represented by S. cerevisiae, Rhodotorula spp. and Debaryomyces
      hansenii, while fish fed yeast contained 4-5 log higher CFU per g of yeast that
      were entirely represented by S. cerevisiae. For gut bacteria, sequencing of 16S
      rRNA gene amplicons using Illumina MiSeq showed lower bacterial diversity and
      abundance of lactic acid bacteria, especially Lactobacillus, in fish reared in
      warm rather than cold water. Fish fed yeast had similar bacterial diversity and
      lower abundance of Leuconostocaceae and Photobacterium compared with fish fed FM.
      CONCLUSIONS: Feeding live yeast mainly increased yeast load in the gut, while
      increased water temperature significantly altered the gut microbiota of rainbow
      trout in terms of bacterial diversity and abundance. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Live yeast can replace 40% of FM without disrupting bacteria
      communities in the gut of rainbow trout, while increased water temperature due to
      seasonal fluctuations and/or climate change may result in a gut dysbiosis that
      may jeopardize the health of farmed fish.

PMID- 29464845
TI  - Monitoring of immunoglobulin A antibodies to epidermal and tissue
      transglutaminases over an 18-month period in a Japanese patient with dermatitis
      herpetiformis.

PMID- 29464846
TI  - Real-life experience of a stent-less revascularization strategy using a
      combination of excimer laser and drug-coated balloon for patients with acute
      coronary syndrome.
AB  - OBJECTIVES: We aimed to test a novel stent-less revascularization strategy using
      a combination of excimer laser coronary angioplasty (ELCA) and drug-coated
      balloon (DCB) for patients with acute coronary syndrome (ACS). BACKGROUND:
      Percutaneous coronary intervention with drug eluting stents is a standard
      invasive treatment for ACS. Some unsolved issues however remain, such as stent
      thrombosis and bleeding risks associated with dual antiplatelet therapy. METHODS:
      Consecutive ACS patients were planned to receive either a DCB application
      following ELCA without a stent implantation or conventional revascularization
      with a coronary stent. The endpoints were (i) major cardiac adverse events
      (MACEs), defined as the composite of cardiac death, myocardial infarctions, and
      target lesion revascularization; (ii) target vessel revascularization (TVR); and
      (iii) angiographic outcome. RESULTS: Since a greater than expected number of
      patients allocated to the stent-less treatment arm eventually received a bailout
      stenting, the following 3 as-treated groups were compared; DCB with ELCA group (N
      = 60), Stent with ELCA group (N = 23), and Stent without ELCA group (N = 85).
      During a mean follow-up period of 420 +/- 137 days, and with angiographic 6- and
      12-month-follow-up rates of 96.7%, 87%, and 81.2%, and 50%, 65.2%, and 45.9%,
      respectively, the MACE rate did not differ across the groups (10%, 4.3%, and
      3.5%; P = 0.22) while an incidence of TVR was more common (15%, 0, and 4.7%; P =
      0.02) and the diameter stenosis at 6-months of follow-up was greater (25.7 +/-
      18.2, 14.9 +/- 13.1 and 16.2 +/- 15.4%; P = 0.002) in the DCB with ELCA group.
      CONCLUSIONS: The stent-less revascularization strategy with DCB and ELCA was
      associated with a higher occurrence of restenosis in ACS patients.

PMID- 29464847
TI  - Clinical efficacy of oral administration of finasteride at a dose of 2.5 mg/day
      in women with female pattern hair loss.
AB  - Female pattern hair loss (FPHL) presents with diffuse thinning over the mid
      frontal scalp, for which various treatment modalities have been tried. Although
      currently, oral 5 alpha-reductase inhibitors such as finasteride are being used,
      their clinical efficacy remains controversial. We retrospectively investigated
      544 premenopausal or postmenopausal patients with FPHL who were prescribed
      finasteride at a dose of 2.5 mg/day. Our study excluded patients with a follow-up
      period of < 3 months and patients who were prescribed other FPHL treatment
      modalities including topical minoxidil. Finally, 112 patients were evaluated
      based on their medical records and clinical photographs. Based on assessment
      using the Ludwig scale at the time of their initial visit, among 112 patients
      studied, 59 patients were classified as belonging to grade I, 47 were grade II,
      and 6 were grade III. Using global photographs, we found that 33 (29.5%) of the
      112 patients studied showed slight improvement, 73 (65.2%) showed significant
      improvement, whereas no change was recorded in 6 (5.4%). We could demonstrate
      efficacy of administration of finasteride at a dose of 2.5 mg/day for patients
      with FPHL and also found that finasteride has a better effect on hair growth when
      patients had a lower Ludwig score and an older age at onset.

PMID- 29464848
TI  - CORM-401 induces calcium signalling, NO increase and activation of pentose
      phosphate pathway in endothelial cells.
AB  - Carbon monoxide-releasing molecules (CO-RMs) induce nitric oxide (NO) release
      (which requires NADPH), and Ca2+ -dependent signalling; however, their
      contribution in mediating endothelial responses to CO-RMs is not clear. Here, we
      studied the effects of CO liberated from CORM-401 on NO production, calcium
      signalling and pentose phosphate pathway (PPP) activity in human endothelial cell
      line (EA.hy926). CORM-401 induced NO production and two types of calcium
      signalling: a peak-like calcium signal and a gradual increase in cytosolic
      calcium. CORM-401-induced peak-like calcium signal, originating from endoplasmic
      reticulum, was reduced by thapsigargin, a SERCA inhibitor, and by dantrolene, a
      ryanodine receptors (RyR) inhibitor. In contrast, the phospholipase C inhibitor
      U73122 did not significantly affect peak-like calcium signalling, but a slow and
      progressive CORM-401-induced increase in cytosolic calcium was dependent on store
      operated calcium entrance. CORM-401 augmented coupling of endoplasmic reticulum
      and plasmalemmal store-operated calcium channels. Interestingly, in the presence
      of NO synthase inhibitor (l-NAME) CORM-401-induced increases in NO and cytosolic
      calcium were both abrogated. CORM-401-induced calcium signalling was also
      inhibited by superoxide dismutase (poly(ethylene glycol)-SOD). Furthermore, CORM
      401 accelerated PPP, increased NADPH concentration and decreased the ratio of
      reduced to oxidized glutathione (GSH/GSSG). Importantly, CORM-401-induced NO
      increase was inhibited by the PPP inhibitor 6-aminonicotinamide (6-AN), but
      neither by dantrolene nor by an inhibitor of large-conductance calcium-regulated
      potassium ion channel (paxilline). The results identify the primary role of CO
      induced NO increase in the regulation of endothelial calcium signalling, that may
      have important consequences in controlling endothelial function.

PMID- 29464849
TI  - In vitro protective effects of an aqueous extract of Clitoria ternatea L. flower
      against hydrogen peroxide-induced cytotoxicity and UV-induced mtDNA damage in
      human keratinocytes.
AB  - The traditional practice of eating the flowers of Clitoria ternatea L. or
      drinking their infusion as herbal tea in some of the Asian countries is believed
      to promote a younger skin complexion and defend against skin aging. This study
      was conducted to investigate the protective effect of C. ternatea flower water
      extract (CTW) against hydrogen peroxide-induced cytotoxicity and ultraviolet (UV)
      induced mitochondrial DNA (mtDNA) damage in human keratinocytes. The protective
      effect against hydrogen peroxide-induced cytotoxicity was determined by 3-(4, 5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      assay, and mtDNA damage induced by UV was determined by polymerase chain
      reaction. Preincubation of HaCaT with 100, 250, and 500 MUg/ml CTW reduced
      cytotoxicity effects of H2 O2 compared with control (H2 O2 alone). CTW also
      significantly reduced mtDNA damage in UV-exposed HaCaT (p < .05). CTW was
      chemically-characterized using high resolution liquid chromatography-mass
      spectrometry. The main compounds detected were assigned as anthocyanins derived
      from delphinidin, including polyacylated ternatins, and flavonol glycosides
      derived from quercetin and kaempferol. These results demonstrated the protective
      effects of C. ternatea flower extracts that contain polyacylated anthocyanins and
      flavonol glycosides as major constituents, against H2 O2 and UV-induced oxidative
      stress on skin cells, and may provide some explanation for the putative
      traditional and cosmetic uses of C. ternatea flower against skin aging.

PMID- 29464850
TI  - Reactions of Metal-Carbon Bonds within Six-Membered Metallaaromatic Rings.
AB  - Metallaaromatics represent a distinct and attractive class of heterocycles, which
      have greatly expanded the library of known aromatics. They have garnered
      extensive research interest on account of their unique properties, organometallic
      reactivity, and aromaticity. The metal-carbon bonds have been regarded as the
      most active reaction sites of metallaaromatics and a variety of related reactions
      have been demonstrated in the literature. This Minireview summarized recent
      findings on the reactivity of the metal-carbon bonds, mainly relevant to the
      representative metallaaromatics with six-membered ring scaffolds. A series of
      reactions occurred on the metal-carbon bonds, including the nucleophilic addition
      reactions, nucleophilic aromatic substitution reactions, electrophilic addition
      reactions, reactions with unsaturated compounds, and migratory insertion
      reactions, have been classified. These reactions demonstrate that the metal
      carbon bonds of metallaaromatics can undergo typical reactions for both aromatic
      species and metal carbene/carbyne complexes. Meanwhile, the reactivity trends of
      the metal-carbon bonds are strongly affected by the metal centers and the effect
      of the corresponding substituents of metallacycles.

PMID- 29464851
TI  - Alteration of GABAergic neurotransmission in Huntington's disease.
AB  - Hereditary Huntington's disease (HD) is characterized by cell dysfunction and
      death in the brain, leading to progressive cognitive, psychiatric, and motor
      impairments. Despite molecular and cellular descriptions of the effects of the HD
      mutation, no effective pharmacological treatment is yet available. In addition to
      well-established alterations of glutamatergic and dopaminergic neurotransmitter
      systems, it is becoming clear that the GABAergic systems are also impaired in HD.
      GABA is the major inhibitory neurotransmitter in the brain, and GABAergic
      neurotransmission has been postulated to be modified in many neurological and
      psychiatric diseases. In addition, GABAergic neurotransmission is the target of
      many drugs that are in wide clinical use. Here, we summarize data demonstrating
      the occurrence of alterations of GABAergic markers in the brain of HD carriers as
      well as in rodent models of the disease. In particular, we pinpoint HD-related
      changes in the expression of GABAA receptors (GABAA Rs). On the basis that a
      novel GABA pharmacology of GABAA Rs established with more selective drugs is
      emerging, we argue that clinical treatments acting specifically on GABAergic
      neurotransmission may be an appropriate strategy for improving symptoms linked to
      the HD mutation.

PMID- 29464852
TI  - Perceptions of driving after marijuana use compared to alcohol use among rural
      American young adults.
AB  - INTRODUCTION AND AIMS: Substance use contributes to motor vehicle crashes, the
      leading cause of death among young adults. The current qualitative study examined
      perceptions of the acceptability and harms associated with driving after
      marijuana versus alcohol use in rural America. Illuminating rural perspectives is
      critical given that the motor vehicle fatality rate is twice as high in rural as
      in urban areas in the USA. DESIGN AND METHODS: In 2015-2016, 72 young adults aged
      18-25 years (Mage  = 20.2; 50.7% female) living in Montana, USA, participated in
      11 focus groups. A list of descriptive codes was generated inductively and two
      individuals coded participant comments. Discussion, memoing and concept mapping
      were used to uncover broader themes and transcripts were reviewed for evidence of
      these themes. RESULTS: There was shared consensus that, with regard to crash
      risk, driving after marijuana use was safer than driving after alcohol use. While
      alcohol was thought to impair driving ability universally, marijuana's impacts
      depended on individual characteristics (e.g. compensatory behaviours) and the
      marijuana itself (e.g. type). Participants expressed conflicting beliefs about
      policies surrounding marijuana use and driving but were more knowledgeable about
      alcohol-related policies. Participants viewed older adults and those in frontier
      areas as more disapproving of driving after marijuana use. DISCUSSION AND
      CONCLUSIONS: Misinformation about the consequences of driving after marijuana use
      is common, demonstrating the need for future research and educational
      interventions. Developing and disseminating guidelines for driving after
      marijuana use would help marijuana users make informed decisions and mitigate
      driving-related risks.

PMID- 29464853
TI  - Quality assessment of clinical practice guidelines for infectious diseases in
      China.
AB  - AIM: We aimed to appraise the quality of Chinese Society of Infectious Diseases
      of China Medical Association clinical practice guidelines (CPGs) for infectious
      diseases in China. METHODS: We performed the electronic search and hand search on
      the above-mentioned CPGs for infectious diseases published from January 1997 to
      October 2017. Each publication was evaluated using the Appraisal of Guidelines
      for Research and Evaluation II (AGREE II) instrument. RESULTS: Thirteen
      guidelines were identified and enrolled for the further evaluation. The median
      scores of the AGREE II domains across all 13 guidelines were as follows: scope
      and purpose 73.61% (36.11% to 84.72%), stakeholder involvement 12.50% (8.33% to
      20.83%), rigor of development 19.27% (12.50% to 26.04%), clarity of presentation
      86.11% (23.61% to 94.44%), applicability 33.33% (26.04% to 50.00%), and editorial
      independence 8.33% (4.17% to 16.67%). The clarity of presentation domain got the
      highest score among the six domains. Moreover, when compared the CPGs by the year
      of publication (2002 to 2006 vs. 2007 to 2017), the quality scores were higher in
      the CPGs published in the last 10 years than those published before, but with no
      significant difference. CONCLUSIONS: The quality score of CPGs for infectious
      diseases in China from January 1997 to October 2017 was moderate, but had
      significant shortcomings, especially in the stakeholder involvement and editorial
      independence domains. However, the AGREE II instrument is useful and feasible for
      appraising the CPGs and should be applied to develop, implement, and promote the
      CPGs in China.

PMID- 29464855
TI  - Luteoloside attenuates anoxia/reoxygenation-induced cardiomyocytes injury via
      mitochondrial pathway mediated by 14-3-3eta protein.
AB  - Ischemia/reperfusion (I/R) injury is the major cause of acute cardiovascular
      disease worldwide. 14-3-3eta protein has been demonstrated to protect myocardium
      against I/R injury. Luteoloside (Lut), a flavonoid found in many Chinese herbs,
      exerts myocardial protection effects. However, the mechanism remains unclear. We
      hypothesize that the cardioprotective role of Lut is exerted by regulating the 14
      3-3eta signal pathway. To investigate our hypothesis, an in vitro I/R model was
      generated in H9C2 cardiomyocytes by anoxia/reoxygenation (A/R) treatment. The
      effects of Lut on cardiomyocytes with A/R injury were assessed by determining the
      cell viability, lactate dehydrogenase levels, intracellular reactive oxygen
      species levels, mitochondrial permeability transition pores (mPTP) openness,
      caspase-3 activity, and apoptosis rate. The effects on protein expression were
      tested using western blot analysis. Lut attenuated A/R-induced injury to
      cardiomyocytes by increasing the expression of 14-3-3eta protein and cell
      viability; decreasing levels of lactate dehydrogenase, reactive oxygen species,
      mPTP openness, caspase-3 activity, and low apoptosis rate were observed. However,
      the cardioprotective effects of Lut were blocked by AD14-3-3etaRNAi, an
      adenovirus knocking down the intracellular 14-3-3eta expression. In conclusion,
      to our knowledge, this is the first study to demonstrate that Lut protected
      cardiomyocytes from A/R-induced injury via the regulation of 14-3-3eta signaling
      pathway.

PMID- 29464856
TI  - Influence of chemoradiotherapy on nutritional status, functional capacity,
      quality of life and toxicity of treatment for patients with cervical cancer.
AB  - AIM: Assess the influence of chemoradiotherapy on the nutritional status,
      functional capacity and quality of life (QoL), associating these indicators at
      baseline with toxicity and interruption of oncologic treatment in women with
      cervical cancer. METHODS: Prospective cohort study performed on 49 women
      diagnosed with cervical cancer, who underwent treatment between August 2015 and
      January 2016. For data collection, two appointments were conducted by the lead
      researcher: the first occurred the day before the first chemotherapy session (T0)
      and the other at the end of chemotherapy session (T1). Nutritional status was
      measured by anthropometry (weight, height, mid-upper arm circumference and
      triceps skinfold thickness) and computed tomography (skeletal muscle index-SMI),
      functional capacity by handgrip strength (HGS) and Karnofsky Performance Status
      (KPS), and application of QoL questionnaire (EORTC QLQ-C30). RESULTS: The average
      age was 45 +/- 13.8 years and 81.6% of the women were diagnosed in stages II and
      III. There was significant reduction in HGS, KPS and QoL between T0 and T1, in
      addition to a significant QoL reduction according to worsening nutritional
      status. The interruption of chemotherapy was significantly associated with the
      variables of nutritional status assessed at baseline. Women who interrupted
      treatment due to acute toxicity also had a significant lower median SMI than
      those who concluded the treatment and 83% of these patients presented cachexia.
      CONCLUSIONS: Chemoradiotherapy treatment in patients with cervical cancer had
      changed negative nutritional parameters, function capacity and QoL, and poor
      nutritional status at baseline was associated with chemotherapy interruption.

PMID- 29464858
TI  - Effects of nurses' emotional intelligence on their organizational citizenship
      behavior, with mediating effects of leader trust and value congruence.
AB  - AIM: To investigate the causal relationship between nurses' emotional
      intelligence and their organizational citizenship behavior and the possible
      mediating effects of leader trust and value congruence. METHODS: The participants
      were 348 nurses who were working in a general hospital in a metropolitan area.
      The data were collected from December 16, 2012 to February 20, 2013. The
      hypothetical model of emotional intelligence, organizational citizenship
      behavior, leader trust, and value congruence was fitted to the actual data via
      structural equation modeling. RESULT: The leaders' emotional intelligence had a
      direct positive effect on leader trust and value congruence; however, the nurses'
      own emotional intelligence had a negative effect on these two variables.
      Furthermore, leader trust had a direct positive effect on organizational
      citizenship behavior; value congruence had no such relationship. The nurses'
      emotional intelligence had a partial, indirect effect on organizational
      citizenship behavior via leader trust. CONCLUSION: In a nursing organization, it
      is necessary to build a system, such as mentoring, to be able to exchange
      emotions actively among the members in order to enhance emotional intelligence
      and have the same values between leaders and members throughout open
      communication. Therefore, nurse managers can contribute greatly to the
      enhancement of organizational performance by promoting members' organizational
      citizenship behavior through improving their relationships with them and gaining
      their trust, while concurrently making efforts to further develop their emotional
      intelligence.

PMID- 29464859
TI  - Growth hormone-releasing peptide 6 prevents cutaneous hypertrophic scarring:
      early mechanistic data from a proteome study.
AB  - Hypertrophic scars (HTS) and keloids are forms of aberrant cutaneous healing with
      excessive extracellular matrix (ECM) deposition. Current therapies still fall
      short and cause undesired effects. We aimed to thoroughly evaluate the ability of
      growth hormone releasing peptide 6 (GHRP6) to both prevent and reverse cutaneous
      fibrosis and to acquire the earliest proteome data supporting GHRP6's acute
      impact on aesthetic wound healing. Two independent sets of experiments addressing
      prevention and reversion effects were conducted on the classic HTS model in
      rabbits. In the prevention approach, the wounds were assigned to topically
      receive GHRP6, triamcinolone acetonide (TA), or vehicle (1% sodium carboxy
      methylcellulose [CMC]) from day 1 to day 30 post-wounding. The reversion scheme
      was based on the infiltration of either GHRP6 or sterile saline in mature HTS for
      4 consecutive weeks. The incidence and appearance of HTS were systematically
      monitored. The sub-epidermal fibrotic core area of HTS was ultrasonographically
      determined, and the scar elevation index was calculated on haematoxylin/eosin
      stained, microscopic digitised images. Tissue samples were collected for
      proteomics after 1 hour of HTS induction and treatment with either GHRP6 or
      vehicle. GHRP6 prevented the onset of HTS without the untoward reactions induced
      by the first-line treatment triamcinolone acetonide (TA); however, it failed to
      significantly reverse mature HTS. The preliminary proteomic study suggests that
      the anti-fibrotic preventing effect exerted by GHRP6 depends on different
      pathways involved in lipid metabolism, cytoskeleton arrangements, epidermal
      cells' differentiation, and ECM dynamics. These results enlighten the potential
      success of GHRP6 as one of the incoming alternatives for HTS prevention.

PMID- 29464860
TI  - Sensing of Vimentin mRNA in 2D and 3D Models of Wounded Skin Using DNA-Coated
      Gold Nanoparticles.
AB  - Wound healing is a highly complex biological process, which is accompanied by
      changes in cell phenotype, variations in protein expression, and the production
      of active biomolecules. Currently, the detection of proteins in cells is done by
      immunostaining where the proteins in fixed cells are detected by labeled
      antibodies. However, immunostaining cannot provide information about dynamic
      processes in living cells, within the whole tissue. Here, an easy method is
      presented to detect the transition of epithelial to mesenchymal cells during
      wound healing. The method employs DNA-coated gold nanoparticle fluorescent
      nanoprobes to sense the production of Vimentin mRNA expressed in mesenchymal
      cells. Fluorescence microscopy is used to achieve temporal detection of Vimentin
      mRNA in wounds. 3D light-sheet microscopy is utilized to observe the dynamic
      expression of Vimentin mRNA spatially around the wounded site in skin tissue. The
      use of DNA-gold nanoprobes to detect mRNA expression during wound healing opens
      up new possibilities for the study of real-time mechanisms in complex biological
      processes.

PMID- 29464861
TI  - Glioma infiltration and extracellular matrix: key players and modulators.
AB  - An outstanding characteristic of gliomas is their infiltration into brain
      parenchyma, a property that impairs complete surgical resection; consequently,
      these tumors might recur, resulting in a high mortality rate. Gliomas invade
      along preferential routes, such as those along white matter tracts and in the
      perineuronal and perivascular spaces. Brain extracellular components and their
      partners and modulators play a crucial role in glioma cell invasion. This review
      presents an extensive survey of the literature, showing how the brain
      extracellular matrix (ECM) is modulated during the glioma infiltration process.
      We explore aspects of ECM interaction with glioma cells, reviewing the main
      glycosaminoglycans, glycoproteins and proteoglycans. We discuss the roles of ECM
      binding proteins, including CD44, RHAMM, integrins and axonal guidance molecules,
      and highlight the role of proteases and glycosidases in glioma infiltration; in
      binding and release chemokines, cytokines and growth factors; and in generating
      new bioactive ECM fragments. We also consider the roles of cytoskeletal
      signaling, angiogenesis, miRNAs and the glial-to-mesenchymal transition linked to
      glioma invasion. We closely discuss therapeutic approaches based on the
      modulation of the extracellular matrix, targeting the control of glioma
      infiltration, its relative failure in clinical trials, and potential means to
      overcome this difficulty.

PMID- 29464862
TI  - Protein Network Analysis and Functional Studies of Calcium Oxalate Crystal
      Induced Cytotoxicity in Renal Tubular Epithelial Cells.
AB  - Our previous expression study has reported a set of proteins with altered levels
      in renal tubular cells after exposure to calcium oxalate monohydrate (COM)
      crystals, which are the main composition of kidney stones. However, their
      functional significance remained largely unknown. In this study, protein network
      analysis revealed that the significantly altered proteins induced by COM crystals
      were involved mainly in three main functional networks, including i) cell
      proliferation and wound healing; ii) oxidative stress and mitochondrial function;
      and iii) cellular junction complex and integrity. Cell proliferation and wound
      healing assays showed that the COM-treated cells had defective proliferation and
      tissue healing capability, respectively. Oxyblot analysis demonstrated
      accumulation of the oxidized proteins, whereas intracellular ATP level was
      significantly increased in the COM-treated cells. Additionally, level of zonula
      occludens-1 (ZO-1), a tight junction protein, was significantly decreased,
      consistent with the significant declines in transepithelial resistance (TER) and
      level of RhoA signaling molecule in the COM-treated cells. These findings
      indicate significant perturbations in mitochondrial and oxidative stress axis
      that cause defective cell proliferation, tissue healing capability, junctional
      protein complex, and cellular integrity of renal tubular epithelial cells exposed
      to COM crystals that may play important roles in kidney stone pathogenesis.

PMID- 29464863
TI  - Change in ALT levels after administration of HMG-CoA reductase inhibitors to
      subjects with pretreatment levels three times the upper normal limit in clinical
      practice.
AB  - AIM: Prescription of statins to patients with chronic liver disease whose alanine
      transaminase (ALT) is over three times the upper normal limit (UNL) is not
      recommended. In this study, we attempted to evaluate patients with baseline ALT
      levels > 3 *  UNL who were prescribed statins without ethical problems, using
      electronic medical records. METHODS: We enrolled subjects with ALT levels > 3 * 
      UNL. The patients were divided into three groups consisting of those who had been
      taking agents affecting liver function (HEPA) and continued to do so after the
      statin prescription (HepCon), those who had not previously taken HEPA and began
      doing so after statin prescription (HepNew), and those who had never taken HEPA
      (HepNo). All ALT levels were determined within 3 months of statins
      administration, and changes were monitored. RESULTS: From January 2009 to
      December 2012, 61 patients with baseline ALT levels > 3 *  UNL were prescribed
      statins for the first time. During the 3-month ALT monitoring, levels of the
      HepCon, HepNew, and HepNo groups decreased by 45 +/- 8%, 64 +/- 10%, and 42 +/-
      8%, respectively; however, intergroup differences were not significant (P =
      .386). All the subjects who were administered statins showed improvement or
      maintained their ALT levels, except for two subjects, which showed deterioration.
      However, the ALT levels of the two subjects subsequently remained stable.
      CONCLUSION: It is not clear whether it is safe to prescribe statins to patients
      with ALT > 3 times the UNL. Our study showed that prescription of statins in
      combination with HEPA did not cause deleterious effects, suggesting that ALT
      levels > 3 times the UNL do not have harmful effects.

PMID- 29464865
TI  - The genus Calea L.: A review on traditional uses, phytochemistry, and biological
      activities.

PMID- 29464864
TI  - Inferences of individual drug responses across diverse cancer types using a novel
      competing endogenous RNA network.
AB  - Differences in individual drug responses are an obstacle to progression in cancer
      treatment, and predicting responses would help to plan treatment. The
      accumulation of cancer molecular profiling and drug response data provides
      opportunities and challenges to identify novel molecular signatures and
      mechanisms of tumor responsiveness to drugs. This study evaluated drug responses
      with a competing endogenous RNA (ceRNA) system that depended on competition
      between diverse RNA species. We identified drug response-related ceRNA (DRCEs) by
      combining the sequence and expression data of long noncoding RNA (lncRNA),
      microRNA (miRNA), and messenger RNA (mRNA), and the survival data of cancer
      patients treated with drugs. We constructed a patient-drug two-layer integrated
      network and used a linear weighting method to predict individual drug responses.
      DRCEs were found to be significantly enriched in known cancer and drug-associated
      data resources, involved in biological processes known to mediate drug responses,
      and correlated to drug activity in cancer cell lines. The dysregulation of DRCE
      expression influenced drug response-associated functions and pathways, suggesting
      DRCEs as potential therapeutic targets affecting drug responses. A further case
      study in breast invasive carcinoma (BRCA) found that DRCE expression was
      consistent with the drug response pattern and the aberrant expression of the two
      NEAT1-related DRCEs may lead to poor response to tamoxifen therapy for patients
      with TP53 mutations. In summary, this study provides a framework for ceRNA-based
      evaluation of clinical drug responses across multiple cancer types. Understanding
      the underlying molecular mechanisms of drug responses will allow improved
      response to chemotherapy and outcomes of cancer treatment.

PMID- 29464866
TI  - Biliary stricture due to a migrated suture after laparoscopic distal gastrectomy.
AB  - Benign biliary strictures have a broad spectrum of etiologies. There have been no
      reported cases, however, of a biliary stricture secondary to a migrated suture
      after laparoscopic distal gastrectomy (LDG). Here, we report one such case. The
      patient was a 60-year-old man who underwent LDG with Roux-en-Y reconstruction for
      early gastric cancer. Pathology revealed early cancer (T1N0M0) with a curative
      resection. Two years after LDG, the patient was found to have elevated
      hepatobiliary enzymes. After further workup, the new diagnosis was invasive
      cholangiocarcinoma (T2N0M0), and the patient underwent pancreaticoduodenectomy.
      Intraoperatively, a monofilament nylon suture was found in the center of a
      biliary stricture; this suture was previously used for duodenal closure during
      LDG. Histologically, the bile duct with stricture showed chronic inflammation and
      fibrosis. Despite no evidence of invasive carcinoma on pathology, a small lesion
      of adenocarcinoma in situ was found in the superior common hepatic duct.

PMID- 29464867
TI  - Blunted cortisol response to stress in patients with eating disorders: Its
      association to bulimic features.
AB  - OBJECTIVE: Clinical research on cortisol response to stress in patients with
      eating disorders has provided controversial and even contradictory results. As
      this might be the consequence of the inclusion in the studies of heterogeneous
      clinical populations, 3 highly selected samples were studied. METHODS:
      Dexamethasone suppression test was performed on 15 restricting anorexia nervosa
      patients without history of bulimia nervosa (BN), 17 BN patients with normal
      weight and no history of anorexia nervosa, and 22 healthy controls. Three days
      later, the Trier Social Stress Test was applied, and 8 saliva samples were
      collected along the trial for cortisol assessment. RESULTS: When the patients
      were considered as a single group, a slightly blunted cortisol response to stress
      was observed, but when the 3 groups were considered separately, the blunted
      response was observed only in the BN patients. DISCUSSION: The results support
      the association between blunted cortisol response and bulimic features.

PMID- 29464868
TI  - An improved strategy for skin lesion detection and classification using uniform
      segmentation and feature selection based approach.
AB  - Melanoma is the deadliest type of skin cancer with highest mortality rate.
      However, the annihilation in early stage implies a high survival rate therefore,
      it demands early diagnosis. The accustomed diagnosis methods are costly and
      cumbersome due to the involvement of experienced experts as well as the
      requirements for highly equipped environment. The recent advancements in
      computerized solutions for these diagnoses are highly promising with improved
      accuracy and efficiency. In this article, we proposed a method for the
      classification of melanoma and benign skin lesions. Our approach integrates
      preprocessing, lesion segmentation, features extraction, features selection, and
      classification. Preprocessing is executed in the context of hair removal by
      DullRazor, whereas lesion texture and color information are utilized to enhance
      the lesion contrast. In lesion segmentation, a hybrid technique has been
      implemented and results are fused using additive law of probability. Serial based
      method is applied subsequently that extracts and fuses the traits such as color,
      texture, and HOG (shape). The fused features are selected afterwards by
      implementing a novel Boltzman Entropy method. Finally, the selected features are
      classified by Support Vector Machine. The proposed method is evaluated on
      publically available data set PH2. Our approach has provided promising results of
      sensitivity 97.7%, specificity 96.7%, accuracy 97.5%, and F-score 97.5%, which
      are significantly better than the results of existing methods available on the
      same data set. The proposed method detects and classifies melanoma significantly
      good as compared to existing methods.

PMID- 29464869
TI  - Identification of the novel HLA-DQB1*06:209 allele in a Chinese individual.
AB  - HLA-DQB1*06:209 has one nucleotide change from HLA-DQB1*06:01:01 at position 260
      G>C in exon 2.

PMID- 29464870
TI  - Older patients' experience of primary hypothyroidism: A qualitative study.
AB  - BACKGROUND: Primary hypothyroidism is a common endocrine disorder, more so in an
      increasing UK ageing population. There is no qualitative research examining the
      older patient perspective of symptoms, treatment and self-management of
      hypothyroidism. OBJECTIVE: In this study we explored the experience of
      hypothyroidism in older people and examined how this may influence their
      understanding and acceptance of diagnosis, treatment with Levothyroxine and the
      monitoring process. DESIGN: We conducted semi-structured interviews with 18
      participants aged between 80 and 93 years. Interview transcripts were analysed
      using a thematic approach. RESULTS: The themes involved older individuals'
      knowledge about symptoms, confidence in diagnosis and understanding of clinical
      management regimen to understand hypothyroidism. Interpretation of the themes was
      informed by the Health Belief Model. CONCLUSION: Our findings can help to inform
      the development of interventions by treating clinicians and support staff to
      engage older patients in the long-term management of this chronic condition.

PMID- 29464871
TI  - Mining the Synergistic Core Allosteric Modules Variation and Sequencing
      Pharmacological Module Drivers in a Preclinical Model of Ischemia.
AB  - Identifying the variation of core modules and hubs seems to be critical for
      characterizing variable pharmacological mechanisms based on topological
      alteration of disease networks. We first identified a total of eight core modules
      by using an approach of multiple modular characteristic fusing (MMCF) from
      different targeted networks in ischemic mice. Interestingly, the value of module
      disturbance intensity (MDI) increased in drug combination group. Second, we
      redefined a weak allosteric module and a strong allosteric module. Then, we
      identified 15 pharmacological module drivers (PMDs) by leave-one-out screening
      with a cutoff of two folds, which were at least, in part, validated by expression
      and variation of topological contribution. Finally, we revealed the fusional and
      emergent variation of PMD in core modules contributing to multidimensional
      synergistic mechanism in ischemic mice and rats. Our findings provide a new set
      of drivers that might promote the pharmacological modular flexibility and offer a
      potential avenue for disease treatment.

PMID- 29464872
TI  - Time-dependent effect of phytocannabinoid treatments in fat cells.
AB  - The objectives of this paper is to investigate, demonstrate, and compare the
      mechanism of action of phytocannabinoids as antidiabetic and anti-obesity agents
      in preadipocytes and adipocytes, relative to rosiglitazone and metformin.
      Briefly, cannabis extract, Delta9 -tetrahydrocannabinol and cannabidiol (in very
      low dosages) were shown to promote glucose uptake higher or to equivalent levels,
      reduce fat accumulation, and reverse the insulin-resistant state of 3T3-L1 cells
      more effectively, relative to rosiglitazone and metformin. The phytocannabinoids
      had a more pronounced effect in preadipocytes undifferentiated model rather than
      the differentiated model. They induced a protective effect at the mitochondrial
      level by preventing overactivity of the succinate dehydrogenase pathway (p <
      .01), unlike rosiglitazone, through activation of the glycerol-3-phosphate
      dehydrogenase shuttling system. An increase in oxygen consumption and an
      increased expression of beta to alpha adrenoceptors (p < .05) in treated cells
      were noted. These findings contribute toward understanding the mechanism of
      action of phytocannabinoids in fat cells and highlight the antidiabetic and anti
      obesity properties of various phytocannabinoids that could potentially support
      the treatment of obesity-related insulin resistance.

PMID- 29464873
TI  - Improving the usefulness of a tool for appraising the quality of qualitative,
      quantitative and mixed methods studies, the Mixed Methods Appraisal Tool (MMAT).
AB  - RATIONALE, AIMS, AND OBJECTIVES: Systematic reviews combining qualitative,
      quantitative, and/or mixed methods studies are increasingly popular because of
      their potential for addressing complex interventions and phenomena, specifically
      for assessing and improving clinical practice. A major challenge encountered with
      this type of review is the appraisal of the quality of individual studies given
      the heterogeneity of the study designs. The Mixed Methods Appraisal Tool (MMAT)
      was developed to help overcome this challenge. The aim of this study was to
      explore the usefulness of the MMAT by seeking the views and experiences of
      researchers who have used it. METHODS: We conducted a qualitative descriptive
      study using semistructured interviews with MMAT users. A purposeful sample was
      drawn from the researchers who had previously contacted the developer of the
      MMAT, and those who have published a systematic review for which they had used
      the MMAT. All interviews were transcribed verbatim and analyzed by 2 coders using
      thematic analysis. RESULTS: Twenty participants from 8 countries were
      interviewed. Thirteen themes were identified and grouped into the 2 dimensions of
      usefulness, ie, utility and usability. The themes related to utility concerned
      the coverage, completeness, flexibility, and other utilities of the tool. Those
      regarding usability were related to the learnability, efficiency, satisfaction,
      and errors that could be made due to difficulties understanding or selecting the
      items to appraise. CONCLUSIONS: On the basis of the results of this study, we
      make several recommendations for improving the MMAT. This will contribute to
      greater usefulness of the MMAT.

PMID- 29464875
TI  - Probing lactate metabolism variations in large-scale bioreactors.
AB  - Lactate metabolism variations are frequently encountered in mammalian cell
      culture processes, especially during process scale-up. In this study, we took a
      multipronged approach to investigate the impact of pH, pCO2 , osmolality, base
      addition, and mixing conditions on the observed lactate variations in a Chinese
      Hamster Ovary (CHO) fed-batch process at 2,000 L scale. Two cultivating methods,
      CO2 -controlled and pH-controlled, were used to decouple the individual and
      synergistic effects from those factors. The individual effects from pH, pCO2 ,
      and osmolality on lactate consumption/reproduction in the stationary phase were
      insignificant in the ranges studied though the initial lactate production rates
      varied. In contrast, lactate metabolism was found to be impacted by an
      interaction between mixing conditions and CO2 accumulation. High CO2 accumulation
      and poor mixing led to lactate reproduction, whereas either low CO2 or improved
      mixing were sufficient to result in lactate consumption. Base addition was not
      required for pH control in the low CO2 conditions, and therefore lactate
      reproduction was correlated with base addition under poor mixing conditions.
      Under good mixing conditions, CO2 -triggered base addition did not significantly
      impact lactate reproduction. It is reasonable to postulate that increased mixing
      times further promoted lactate production during base addition. As lactate
      reproduction results in more base addition to maintain pH, a cycle could be
      formed between lactate production and base addition. As a remediation, we showed
      that such lactate reproduction could be eliminated by improving CO2 removal at
      2,000 L scale. (c) 2018 American Institute of Chemical Engineers Biotechnol.
      Prog., 34:756-766, 2018.

PMID- 29464874
TI  - The efficacy of adding targeted agents to neoadjuvant therapy for locally
      advanced rectal cancer patients: a meta-analysis.
AB  - Patients with locally advanced rectal cancer (LARC) are at tremendous risk of
      metastatic diseases. To improve the prognoses of LARC patients, the efficacy of
      adding targeted agents to neoadjuvant therapy has been investigated by many
      researchers but remains controversial. A literature search of relevant databases
      was conducted through December 2016, 804 studies were identified and 32
      investigations were ultimately included. A total of 1196 patients from 31 cohorts
      of 29 studies were eligible for quantitative synthesis in this single-arm setting
      meta-analysis. As pathologic complete response (pCR) shows promise as a prognosis
      indicator, we focused on pCR rates to evaluate whether adding targeted agents to
      neoadjuvant therapies improves the outcome of LARC patients. In our study, we
      revealed pooled estimates of pCR of 27% (95%CI, 21-34%) and 14% (95%CI, 9-21%)
      for bevacizumab-relevant cohorts and cetuximab-relevant cohorts, respectively.
      The safety of adding targeted agents to neoadjuvant therapy was also evaluated by
      pooling the data of Grade 3/4 toxicity. In conclusion, our study revealed that
      adding bevacizumab to the neoadjuvant therapy regimens provides appreciable pCR
      for LARC patients. Meanwhile, the efficacy of cetuximab remains inconclusive,
      RCTs with larger scale and better study design that stress more on mutational
      status are needed.

PMID- 29464876
TI  - Pilot towards developing a school mental health service: Experiences and lessons
      learnt in implementing Kenya integrated intervention model for dialogue and
      screening to promote children's mental well-being.
AB  - AIM: This paper aims at documenting the process of implementing "Kenya Integrated
      intervention model for Dialogue and Screening to promote children's mental
      wellbeing (KIDS)", with emphasis on activities, experiences, challenges and
      lessons learnt through the process that can inform improvement in Kenya and other
      social-economically and culturally similar settings. METHODS: KIDS aimed at
      providing early and integrated culturally acceptable intervention to promote
      child mental health in 6 to 13 year olds, targeting 5429 children in 24 schools.
      It was a pilot study conducted in 2 administrative counties in Kenya (Machakos
      and Makueni). The main goal of this study was to test the efficacy and
      feasibility of the proposed model that incorporated several significant
      stakeholders. RESULTS: The implementation of KIDS was grouped into 6 stepwise and
      2 ongoing processes: (1) Stakeholder engagement and collaboration; (2) Selecting,
      adapting, translating, piloting and adopting the study tools; (3) Conducting
      Participatory Theory of Change (ToC); (4) Building the capacity of the key
      implementing partners; (5) Community awareness and psycho-education, (6) Using
      school-based life skills and peer clubs counselling to provide psychosocial
      support; (7) Ongoing monitoring, supervision and quality assurance and (8)
      Ongoing knowledge exchange and dissemination. Specific logistical challenges and
      possible solutions for future school mental health services are also stated in
      this article. CONCLUSION: KIDS is a feasible model for school mental health
      service programme in Kenya but there are challenges which provide innovative
      opportunities for better designed school mental health services programme.

PMID- 29464877
TI  - Patient navigation for lung cancer screening among current smokers in community
      health centers a randomized controlled trial.
AB  - Annual chest computed tomography (CT) can decrease lung cancer mortality in high
      risk individuals. Patient navigation improves cancer screening rates in
      underserved populations. Randomized controlled trial was conducted from February
      2016 to January 2017 to evaluate the impact of a patient navigation program on
      lung cancer screening (LCS) among current smokers in five community health
      centers (CHCs) affiliated with an academic primary care network. We randomized
      1200 smokers aged 55-77 years to intervention (n = 400) or usual care (n = 800).
      Navigators contacted patients to determine LCS eligibility, introduce shared
      decision making about screening, schedule appointments with primary care
      physicians (PCPs), and help overcome barriers to obtaining screening and follow
      up. Control patients received usual care. The main outcome was the proportion of
      patients who had any chest CT. Secondary outcomes were the proportion of patients
      contacted, proportion receiving LCS CTs, screening results and number of lung
      cancers diagnosed. Of the 400 intervention patients, 335 were contacted and 76
      refused participation. Of the 259 participants, 124 (48%) were ineligible for
      screening; 119 had smoked <30 pack-years, and five had competing comorbidities.
      Among the 135 eligible participants in the intervention group, 124 (92%) had any
      chest CT performed. In intention-to-treat analyses, 124 intervention patients
      (31%) had any chest CT versus 138 control patients (17.3%, P < 0.001). LCS CTs
      were performed in 94 intervention patients (23.5%) versus 69 controls (8.6%, P <
      0.001). A total of 20% of screened patients required follow-up. Lung cancer was
      diagnosed in eight intervention (2%) and four control (0.5%) patients. A patient
      navigation program implemented in CHCs significantly increased LCS among high
      risk current smokers.

PMID- 29464878
TI  - A blood tumor marker combination assay produces high sensitivity and specificity
      for cancer according to the natural history.
AB  - Diagnosis using a specific tumor marker is difficult because the sensitivity of
      this detection method is under 20%. Herein, a tumor marker combination assay,
      combining growth-related tumor marker and associated tumor marker (Cancer, 73(7),
      1994), was employed. This double-blind tumor marker combination assay (TMCA)
      showed 87.5% sensitivity as the results, but a low specificity, ranging from 30
      to 76%. To overcome this low specificity, we exploited complex markers, a
      multivariate analysis and serum fractionation by biochemical biopsy. Thus, in
      this study, a combination of new techniques was used to re-evaluate these serum
      samples. Three serum panels, containing 90, 120, and 97 samples were obtained
      from the Mayo Clinic. The final results showed 80-90% sensitivity, 84-85%
      specificity, and 83-88% accuracy. We demonstrated a notable tumor marker
      combination assay with high accuracy. This TMCA should be applicable for primary
      cancer detection and recurrence prevention.

PMID- 29464879
TI  - Insights into implementation of sacubitril/valsartan into clinical practice.
AB  - BACKGROUND: Sacubitril/valsartan significantly reduced heart failure
      hospitalization and mortality in PARADIGM-HF (Prospective Comparison of
      Angiotensin Receptor-Neprilysin Inhibitor With an Angiotensin-Converting Enzyme
      Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart
      Failure). However, real-world data from its use are lacking. METHODS AND RESULTS:
      We retrospectively assessed all baseline and follow-up data of consecutive heart
      failure patients with reduced ejection fraction receiving therapy with
      sacubitril/valsartan for Class I recommendation between December 2016 and July
      2017. Baseline characteristics and dose titration of sacubitril/valsartan were
      compared between patients in clinical practice and in PARADIGM-HF. A total of 120
      patients (81% male) were switched from angiotensin-converting enzyme inhibitor or
      angiotensin receptor blocker to sacubitril/valsartan. A total of 20.1% of
      patients received dose uptitration. Patients were treated with an equipotential
      dose of renin-angiotensin system blockers before and after uptitration of
      sacubitril/valsartan (57 +/- 29% vs. 53 +/- 29% of target dose indicated by
      European Society of Cardiology guidelines; P = 0.286). However, they received a
      lower dose of sacubitril/valsartan in comparison with those in the PARADIGM-HF
      (219 +/- 12 vs. 375 +/- 75 mg; P < 0.001). In comparison with the patients
      receiving sacubitril/valsartan in PARADIGM-HF, patients in clinical practice were
      older and had a higher serum creatinine, higher New York Heart Association
      functional classification, and lower left ventricular ejection fraction (all P
      value <0.05). Even in comparison with patients who experienced dropout during the
      run-in phase of PARADIGM-HF, real-world patients exhibited baseline
      characteristics indicative of more disease severity. Patients were at high
      absolute baseline risk for adverse outcome as illustrated by the EMPHASIS-HF
      (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure)
      risk score of 6 (inter-quartile range 3), in comparison with 5 (inter-quartile
      range 4) in PARADIGM-HF. After initiation of sacubitril/valsartan, New York Heart
      Association class significantly improved (P < 0.001), but systolic blood pressure
      dropped more than was reported in PARADIGM-HF (7.1 +/- 8.0 vs. 3.2 +/- 0.4 mmHg;
      P < 0.001). CONCLUSIONS: Patients in clinical practice exhibit baseline
      characteristics associated with more severe disease, which might lead to
      prescription of lower doses. Nevertheless, patients in clinical practice are at
      high risk of adverse outcome as illustrated by the EMPHASIS-HF risk score,
      underscoring the large potential for sacubitril/valsartan therapy to reduce the
      risk of heart failure hospitalization and all-cause mortality.

PMID- 29464880
TI  - Spatial elongation of population receptive field profiles revealed by model-free
      fMRI back-projection.
AB  - Estimates of visual field topographies in human visual cortex obtained through
      fMRI traveling wave techniques usually provide the parameters of population
      receptive field (pRF) location (polar angle, eccentricity) and receptive field
      size. These parameters are obtained by fitting the recorded data to a standard
      model population receptive field. In this work, pRF profiles are measured
      directly by back-projecting preprocessed fMRI time-series to sweeps of a bar
      across the visual field in different angles. The current data suggest that the
      model-free pRF profiles contain information not only about receptive field
      location and size but also about the pRF shape characteristics. The elongation
      (ellipticity) of pRFs decreases along the early visual hierarchy to a different
      degree for the ventral and the dorsal stream. Furthermore, ellipticity changes as
      a function of eccentricity. pRF orientation shows a high degree of collinearity
      with its angular position within the visual field. Using model-free pRF
      measurements, the traveling wave technique provides additional characteristics of
      pRF topographies that are not restricted to size and provide robust measures
      within the single subject.

PMID- 29464881
TI  - Cytologic features of needle aspiration of ovarian sex cord tumor with annular
      tubules: Report of two cases and literature review.
AB  - Sex cord tumor with annular tubules (SCTAT) is a rare ovarian tumor with
      characteristic microscopic morphologic features. Diagnosis most often is based on
      examination of tissue specimens. Cytologic features of this tumor rarely have
      been described in the English literature. Herein, we report cytologic findings of
      cyst aspiration fluid in two cases of SCTAT, with cyto-histologic correlation.

PMID- 29464882
TI  - Designed Precursor for the Controlled Synthesis of Highly Active Atomic and Sub
      nanometric Platinum Catalysts on Mesoporous Silica.
AB  - The development of new methods to synthesize nanometric metal catalysts has
      always been an important and prerequisite step in advanced catalysis. Herein, we
      design a stable nitrogen ligated Pt complex for the straightforward synthesis by
      carbonization of uniformly sized atomic and sub-nanometric Pt catalysts supported
      on mesoporous silica. During the carbonization of the Pt precursor into active Pt
      species, the nitrogen-containing ligand directed the decomposition in a
      controlled fashion to maintain uniform sizes of the Pt species. The nitrogen
      ligand had a key role to stabilize the single Pt atoms on a weak anchoring
      support like silica. The Pt catalysts exhibited remarkable activities in the
      hydrogenation of common organic functional groups with turnover frequencies
      higher than in previous studies. By a simple post-synthetic treatment, we could
      selectively remove the Pt nanoparticles to obtain a mixture of single atoms and
      nanoclusters, extending the applicability of the present method.

PMID- 29464883
TI  - High-intensity interval training improves acute plasma volume responses to
      exercise that is age dependent.
AB  - Plasma volume (PV) is affected by several factors including age, physical
      training and, acutely, by exercise intensity. The purpose of this study was to
      investigate the effects of 6 weeks of high-intensity interval training (HIT) on
      PV and blood pressure (BP) changes among sedentary individuals. Thirty subjects
      aged between 18 and 71 years [body mass index=30.1(1.2) kg/m2 ] completed a 6
      weeks HIT program. Anthropometric and fitness variables were obtained at pre- and
      post- HIT. PV variations during warm-up and after supramaximal cycling test (SCT)
      were calculated using two methods based on Hematocrit (Ht) and Hemoglobin (Hb)
      measures. After both the warm-up and SCT, PV decreased significantly among
      participants at pre- and at post-HIT (P < 0.01). However, PV decreases were
      significantly greater at pre-HIT compared with post-HIT during warm-up and after
      SCT (P < 0.01, respectively). In addition, at pre-HIT, a positive relationship
      was found between age and both PV variations at warm-up and after SCT (r2  = 0.55
      and r2  = 0.46; P < 0.01 respectively). However, no relationship was found during
      the post-HIT period. After SCT and after both visits, only body weight predicted
      22% of PV variations. In the current study, a significant relationship was found
      between systolic and diastolic BP improvements and PV variations in post-HIT (r2 
      = 0.54 and r2 =0.56, P < 0.05, respectively). Our results suggest that HIT may
      improve PV values and reduce the effects of age on the decrease in PV. These
      interventions led to improvements in systolic and diastolic BP values among
      participants.

PMID- 29464884
TI  - Swept source optical coherence tomography findings of tuberous sclerosis
      associated retinal astrocytoma.

PMID- 29464886
TI  - Abstracts of the Urological Society of Australia and New Zealand 71st Annual
      Scientific Meeting, Melbourne, Australia, 24-27 February 2018.

PMID- 29464885
TI  - Effect of Roux-en-Y gastric bypass on liver mitochondrial dynamics in a rat model
      of obesity.
AB  - Bariatric surgery provides significant and durable improvements in glycemic
      control and hepatic steatosis, but the underlying mechanisms that drive
      improvements in these metabolic parameters remain to be fully elucidated.
      Recently, alterations in mitochondrial morphology have shown a direct link to
      nutrient adaptations in obesity. Here, we evaluate the effects of Roux-en-Y
      gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics in a
      diet-induced obesity Sprague-Dawley (SD) rat model. Livers were harvested from
      adult male SD rats 90-days after either Sham or RYGB surgery and continuous high
      fat feeding. We assessed expression of mitochondrial proteins involved in fusion,
      fission, mitochondrial autophagy (mitophagy) and biogenesis, as well as
      differences in citrate synthase activity and markers of oxidative stress. Gene
      expression for mitochondrial fusion genes, mitofusin 1 (Mfn1; P < 0.05),
      mitofusin 2 (Mfn2; P < 0.01), and optic atrophy 1 (OPA1; P < 0.05) increased
      following RYGB surgery. Biogenesis regulators, peroxisome proliferator-activated
      receptor gamma coactivator 1-alpha (PGC1alpha; P < 0.01) and nuclear respiratory
      factor 1 (Nrf1; P < 0.05), also increased in the RYGB group, as well as mitophagy
      marker, BCL-2 interacting protein 3 (Bnip3; P < 0.01). Protein expression for
      Mfn1 (P < 0.001), PGC1alpha (P < 0.05), BNIP3 (P < 0.0001), and mitochondrial
      complexes I-V (P < 0.01) was also increased by RYGB, and Mfn1 expression
      negatively correlated with body weight, insulin resistance, and fasting plasma
      insulin. In the RYGB group, citrate synthase activity was increased (P < 0.02)
      and reactive oxygen species (ROS) was decreased compared to the Sham control
      group (P < 0.05), although total antioxidant capacity was unchanged between
      groups. These data are the first to show an association between RYGB surgery and
      improved markers of liver mitochondrial dynamics. These observed improvements may
      be related to weight loss and reduced energetic demand on the liver, which could
      facilitate normalization of glucose homeostasis and protect against hepatic
      steatosis.

PMID- 29464887
TI  - Factitious hypoglycemia in children and adolescents with diabetes.
AB  - BACKGROUND: Factitious hypoglycemia is a condition of self-induced hypoglycemia
      due to surreptitious administration of insulin or oral hypoglycemic agents. In
      adults, it is an uncommon, but well known clinical entity observed in individuals
      with and without diabetes. OBJECTIVES: To report a case of factitious
      hypoglycemia highlighting diagnostic pitfalls, to identify common characteristics
      of children and adolescents with factitious hypoglycemia, and to examine whether
      the information on long-term outcome exists. METHODS: We present a case of an
      adolescent with type 1 diabetes who had self-induced hypoglycemia of several
      years' duration; and we conducted a systematic literature review on factitious
      hypoglycemia in pediatric patients with diabetes. RESULTS: We identified a total
      of 83 articles of which 14 met the inclusion criteria (describing 39 cases). All
      but 1 individual had type 1 diabetes and the majority was female (63%). Average
      age was 13.5 +/- 2.0 years with the youngest patient presenting at the age 9.5
      years. Blood glucose control was poor (hemoglobin A1c: 12.1 +/- 4.0%). In 35%,
      psychiatric disorders were mentioned as contributing factors. Only 3 reports
      provided follow-up beyond 6 months. CONCLUSIONS: Factitious hypoglycemia
      typically occurs in adolescents with type 1 diabetes who use insulin to induce
      hypoglycemia. Awareness of this differential diagnosis and knowledge of
      potentially misleading laboratory results may facilitate earlier recognition and
      intervention. Little information exists on effective treatments and long-term
      outcome.

PMID- 29464888
TI  - Postoperative cytological findings from the use of the Integran microfibrillar
      collagen hemostatic matrix in conization.
AB  - The Integran microfibrillar collagen hemostatic matrix is one form of
      microfibrillar collagen hemostat. This form has a sheet-type structure and has
      explicitly been used in Japan. In gynecology, this sheet-type matrix has helped
      effect uterine surface hemostasis, especially in myomectomy and cervical
      conization. However, cytotechnologists and pathologists have overlooked the
      foreign materials used for conization in postoperative cervical cytology. We
      report two cases describing the characteristic cervical cytology findings when
      Integran was used in conization. The first case was a 67-year-old woman who
      underwent conization because of cervical intraepithelial neoplasia (CIN) 3.
      Thirty-six days after the surgery, many cylindrical fragments of glossy acellular
      materials appeared in the cervical cytology. Fortunately, the content did not
      impede the diagnosis of NILM. The patient then underwent hysterectomy two months
      after conization. Surgical specimen revealed a high degree of inflammation and
      granulation without malignancy. Following surgery, the cylindrical fragments
      disappeared from microscopic findings. The second case was a 45-year-old woman
      who underwent conization because of CIN3. Thirty-four days after the surgery,
      many tubular pieces of glossy acellular materials appeared in cervical cytology,
      as seen in the first case. The cytological diagnosis was NILM. One hundred days
      after surgery, cervical cytology revealed many clue cells but no cylindrical
      fragments. These clusters of cylindrical fragments of glossy acellular materials
      in cervical cytology after conization might induce a delay in diagnosing the
      persistence and recurrence of cervical cancer. This article is the first report
      describing cervical cytology findings associated with Integran use.

PMID- 29464889
TI  - Immediate mandibular reconstruction via patient-specific titanium mesh tray using
      electron beam melting/CAD/rapid prototyping techniques: One-year follow-up.
AB  - BACKGROUND: Immediate mandibular reconstruction was performed using a patient
      specific titanium mesh tray fabricated by electron beam melting (EBM) /rapid
      prototyping techniques. METHODS: Patient-specific titanium trays were virtually
      designed and fabricated using EBM technology/rapid prototyping for patients
      requiring mandibular resection and immediate reconstruction using an iliac crest
      bone graft. Dental implants were placed in the grafted sites and the patients
      received prosthetic rehabilitation with a follow-up of one year. Clinical data,
      postoperative bone formation and complications were evaluated. RESULTS: A
      symmetric appearance of facial contours was achieved. The titanium tray
      incorporated the particulate iliac crest bone graft that provided significant
      bone formation (mean 18.97 +/- 1.45 mm) and predictable results. Stability of the
      dental implants was achieved. CONCLUSION: The patient-specific titanium meshes
      and immediate particulate autogenous bone graft showed satisfactory clinical and
      surgical results in improving patients' quality of life and decreasing the
      overall treatment time with adequate functional rehabilitation.

PMID- 29464890
TI  - Serelaxin induces Notch1 signaling and alleviates hepatocellular damage in
      orthotopic liver transplantation.
AB  - Liver ischemia-reperfusion injury (IRI) represents a risk factor for early graft
      dysfunction and an obstacle to expanding donor pool in orthotopic liver
      transplantation (OLT). We have reported on the crucial role of macrophage Notch1
      signaling in mouse warm hepatic IRI model. However, its clinical relevance or
      therapeutic potential remain unknown. Here, we used Serelaxin (SER), to verify
      Notch1 induction and putative hepatoprotective function in ischemia-reperfusion
      stressed OLT. C57BL/6 mouse livers subjected to extended (18-hour) cold storage
      were transplanted to syngeneic recipients. SER treatment at reperfusion
      ameliorated IRI, improved post-OLT survival, decreased neutrophil/macrophage
      infiltration, and suppressed proinflammatory cytokine programs, while
      simultaneously increasing Notch intracellular domain (NICD) and hairy and
      enhancer of split 1 (Hes1) target genes. In bone marrow-derived macrophage
      cultures, SER suppressed proinflammatory while enhancing antiinflammatory gene
      expression concomitantly with increased NICD and Hes1. Hepatic biopsies from 21
      adult primary liver transplant patients (2 hours postreperfusion) were divided
      into low-NICD (n = 11) and high-NICD (n = 10) expression groups (western blots).
      Consistent with our murine findings, human livers characterized by high NICD were
      relatively IRI resistant, as shown by serum alanine aminotransferase (ALT) levels
      at day 1 post-OLT. Our study documents the efficacy of SER-Notch1 signaling in
      mouse OLT and highlights the protective function of Notch1 in liver transplant
      patients.

PMID- 29464891
TI  - Continuous glucose monitoring: a review of the evidence, opportunities for future
      use and ongoing challenges.
AB  - The advent of devices that can track interstitial glucose levels, which are
      closely related to blood glucose levels, on a near continuous basis, has
      facilitated better insights into patterns of glycaemia. Continuous glucose
      monitoring (CGM) therefore allows for more intensive monitoring of blood glucose
      levels and potentially improved glycaemic control. In the context of the
      announcement on 1 April 2017 that the Australian Government will fund CGM
      monitoring for people with type 1 diabetes under the age of 21 years, this paper
      provides a review of the evidence for CGM and some of the ongoing challenges.
      There is evidence that real-time CGM in type 1 diabetes improves HbA1c and
      hypoglycaemia, while in type 2 diabetes, the evidence is less robust. Initial
      barriers to widespread implementation of CGM included issues with accuracy and
      user friendliness; however, as the technology has evolved, these issues have
      largely improved. Ongoing barriers include cost, and weaker evidence for their
      benefit in certain populations such as those with type 2 diabetes and less
      glycaemic variability. CGM has the potential to reduce healthcare costs, although
      real-world studies, including cost-effectiveness analyses, are needed in this
      area.

PMID- 29464892
TI  - Evaluation of differences between dual salt-pH gradient elution and mono gradient
      elution using a thermodynamic model: Simultaneous separation of six monoclonal
      antibody charge and size variants on preparative-scale ion exchange
      chromatographic resin.
AB  - The efficiencies of mono gradient elution and dual salt-pH gradient elution for
      separation of six mAb charge and size variants on a preparative-scale ion
      exchange chromatographic resin are compared in this study. Results showed that
      opposite dual salt-pH gradient elution with increasing pH gradient and
      simultaneously decreasing salt gradient is best suited for the separation of
      these mAb charge and size variants on Eshmuno(r) CPX. Besides giving high binding
      capacity, this type of opposite dual salt-pH gradient also provides better
      resolved mAb variant peaks and lower conductivity in the elution pools compared
      to single pH or salt gradients. To have a mechanistic understanding of the
      differences in mAb variants retention behaviors of mono pH gradient, parallel
      dual salt-pH gradient, and opposite dual salt-pH gradient, a linear gradient
      elution model was used. After determining the model parameters using the linear
      gradient elution model, 2D plots were used to show the pH and salt dependencies
      of the reciprocals of distribution coefficient, equilibrium constant, and
      effective ionic capacity of the mAb variants in these gradient elution systems.
      Comparison of the 2D plots indicated that the advantage of opposite dual salt-pH
      gradient system with increasing pH gradient and simultaneously decreasing salt
      gradient is the noncontinuous increased acceleration of protein migration.
      Furthermore, the fitted model parameters can be used for the prediction and
      optimization of mAb variants separation in dual salt-pH gradient and step
      elution. (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog.,
      34:973-986, 2018.

PMID- 29464894
TI  - Fine needle aspiration of pilomatrixoma: Cytologic features on thinprep and
      diagnostic pitfalls.

PMID- 29464893
TI  - Improvements in fitness are not obligatory for exercise training-induced
      improvements in CV risk factors.
AB  - The purpose of this study was to assess whether changes in physical fitness
      relate to changes in cardiovascular risk factors following standardized, center
      based and supervised exercise training programs in subjects with increased
      cardiovascular risk. We pooled data from exercise training studies of subjects
      with increased cardiovascular risk (n = 166) who underwent 8-52 weeks endurance
      training. We determined fitness (i.e., peak oxygen uptake) and traditional
      cardiovascular risk factors (body mass index, blood pressure, total cholesterol,
      high-density lipoprotein cholesterol), before and after training. We divided
      subjects into quartiles based on improvement in fitness, and examined whether
      these groups differed in terms of risk factors. Associations between changes in
      fitness and in cardiovascular risk factors were further tested using Pearson
      correlations. Significant heterogeneity was apparent in the improvement of
      fitness and individual risk factors, with nonresponder rates of 17% for fitness,
      44% for body mass index, 33% for mean arterial pressure, 49% for total
      cholesterol, and 49% for high-density lipoprotein cholesterol. Neither the
      number, nor the magnitude, of change in cardiovascular risk factors differed
      significantly between quartiles of fitness change. Changes in fitness were not
      correlated with changes in cardiovascular risk factors (all P > 0.05). Our data
      suggest that significant heterogeneity exists in changes in peak oxygen uptake
      after training, while improvement in fitness did not relate to improvement in
      cardiovascular risk factors. In subjects with increased cardiovascular risk,
      improvements in fitness are not obligatory for training-induced improvements in
      cardiovascular risk factors.

PMID- 29464895
TI  - Selective extraction of lipase and amylase from enzyme mixture by employing
      liquid emulsion membrane.
AB  - This work deals with the extraction of lipase and amylase from enzyme mixture by
      employing liquid emulsion membranes (LEM). The electrostatic interaction between
      enzymes and reverse micellar surfactant polar head group plays an important role
      for selective extraction of two different enzymes having different isoelectric
      points. The optimized conditions for lipase extraction (pH 7.0) resulted in the
      purification fold and activity recovery of 5.43 fold and 89.53%, respectively,
      whereas, in case of amylase (pH 9.0) the purification fold and activity recovery
      were 6.58 and 94.32%, respectively. The results were compared with the control
      sample (containing individual enzymes) and mixture of enzymes lipase and amylase
      and it was shown that for optimum conditions the activity recovery and
      purification fold was higher for the individual enzymes as compared to their
      mixture. Downstream processing involving LEM was shown to be a feasible method
      for selective extraction of enzymes. (c) 2018 American Institute of Chemical
      Engineers Biotechnol. Prog., 34:721-729, 2018.

PMID- 29464896
TI  - Corticostriatal network dysfunction in Huntington's disease: Deficits in neural
      processing, glutamate transport, and ascorbate release.
AB  - AIMS: This review summarizes evidence for dysfunctional connectivity between
      cortical and striatal neurons in Huntington's disease (HD), a fatal
      neurodegenerative condition caused by a single gene mutation. The focus is on
      data derived from recording of electrophysiological signals in behaving
      transgenic mouse models. DISCUSSIONS: Firing patterns of individual neurons and
      the frequency oscillations of local field potentials indicate a disruption in
      corticostriatal processing driven, in large part, by interactions between cells
      that contain the mutant gene rather than the mutant gene alone. Dysregulation of
      glutamate, an excitatory amino acid released by cortical afferents, plays a key
      role in the breakdown of corticostriatal communication, a process modulated by
      ascorbate, an antioxidant vitamin found in high concentration in striatum. Up
      regulation of glutamate transport by drug administration or viral-vector delivery
      improves ascorbate homeostasis and neurobehavioral processing in HD mice. Further
      analysis of electrophysiological data, including the use of sophisticated
      computational strategies, is required to discern how behavioral demands modulate
      the flow of corticostriatal information and its disruption by HD. CONCLUSIONS:
      Long before massive cell loss occurs, HD impairs the mechanisms by which cortical
      and striatal neurons communicate. A key problem identified in transgenic animal
      models is dysregulation of the dynamic changes in extracellular glutamate and
      ascorbate. Improved understanding of how these neurochemical systems impact
      corticostriatal communication is necessary before an effective therapeutic
      strategy can emerge.

PMID- 29464897
TI  - Case report of neuroleptic malignant syndrome with prolonged mental changes and
      severe dyskinesia.

PMID- 29464898
TI  - Matching donor and recipient based on predicted indirectly recognizable human
      leucocyte antigen epitopes.
AB  - The predicted indirectly recognizable human leucocyte antigen (HLA) epitopes
      (PIRCHE) algorithm is a novel in silico algorithm to determine donor-recipient
      compatibility. The PIRCHE algorithm determines donor-recipient compatibility by
      counting the number of mismatched HLA-derived epitopes that are involved in
      indirect T-cell alloimmune responses; these epitopes are designated as PIRCHE.
      Over the last few years, the PIRCHE algorithm has been investigated in both
      hematopoietic stem cell transplantation and solid organ transplantation. This
      review describes the theory of the algorithm, its application in transplantation,
      and highlights the future perspectives on the clinical application of the PIRCHE
      algorithm.

PMID- 29464899
TI  - Proteomic Adaptation of Australian Epidemic Bordetella pertussis.
AB  - Bordetella pertussis causes whooping cough. The predominant strains in Australia
      changed to single nucleotide polymorphism (SNP) cluster I (pertussis toxin
      promoter allele ptxP3/pertactin gene allele prn2) from cluster II (non-ptxP3/non
      prn2). Cluster I was mostly responsible for the 2008-2012 Australian epidemic and
      was found to have higher fitness compared to cluster II using an in vivo mouse
      competition assay, regardless of host's immunization status. This study aimed to
      identify proteomic differences that explain higher fitness in cluster I using
      isobaric tags for relative and absolute quantification (iTRAQ), and high
      resolution multiple reaction monitoring (MRM-hr). A few key differences in the
      whole cell and secretome were identified between the cluster I and II strains
      tested. In the whole cell, nine proteins were upregulated (>1.2 fold change, q <
      0.05) and three were downregulated (<0.8 fold change, q < 0.05) in cluster I. One
      downregulated protein was BP1569, a TLR2 agonist for Th1 immunity. In the
      secretome, 12 proteins were upregulated and 1 was downregulated which was Bsp22,
      a type III secretion system (T3SS) protein. Furthermore, there was a trend of
      downregulation in three T3SS effectors and other virulence factors. Three
      proteins were upregulated in both whole cell and supernatant: BP0200, molybdate
      ABC transporter (ModB), and tracheal colonization factor A (TcfA). Important
      expression differences in lipoprotein, T3SS, and transport proteins between the
      cluster I and II strains were identified. These differences may affect immune
      evasion, virulence and metabolism, and play a role in increased fitness of
      cluster I.

PMID- 29464900
TI  - Abnormal scattergrams and cell population data generated by fully automated
      hematological analyzers: New tools for screening malaria infection?
AB  - INTRODUCTION: Malaria is a life-threatening infectious disease, which has been
      for long confined to specific endemic areas. Nevertheless, the recent increase in
      immigration flows from endemic regions and imported cases has reemphasized many
      diagnostic challenges in Western countries, thus paving the way to introduce
      rapid and accurate strategies for screening subjects with suspected Malaria
      infection. Therefore, the aim of this article was to describe our recent
      experience with Sysmex XN-module for rapid screening of subjects with suspected
      Malaria. METHODS: Fourteen patients admitted to the Emergency Department (Papa
      Giovanni XXIII Hospital Bergamo, Italy) with a clinical suspicion of Malaria
      infection were evaluated, along with 1047 control samples. The analysis of
      peripheral blood was performed with XN-module, and results were then compared to
      optical microscopy. RESULTS: Nine patients were positive to Plasmodim falciparum,
      3 to Plasmodim vivax, one to Plasmodim ovale, and one to Plasmodim malarie.
      Characteristic abnormalities could be observed in both white blood cell
      differential (WDF) and white cell nucleated (WNR) scattergrams (sensitivity 0.64
      and specificity 1.0) in 9 samples with parasites at gametocyte or schizos stage
      irrespective of Plasmodium species and parasitic index, while characteristic
      scattergram abnormalities could not be seen in the 5 samples containing only
      parasites at the trophozoites stage. In these cases, specific variations of some
      cell population data (CPD) could be recorded (sensitivity 1.00 and specificity
      0.91). CONCLUSION: The peculiar abnormalities observed in CPDs, WDF, and WNR
      scattergrams may raise a definite suspicion of Malaria infection. Further studies
      should then be planned for validating these preliminary findings and assessing
      whether these specific abnormalities may be incorporated in rapid and inexpensive
      Malaria diagnostic algorithms.

PMID- 29464901
TI  - Longitudinal evaluation of posterior corneal changes after laser in situ
      keratomileusis in high myopia: a swept-source optical coherence tomography study.

PMID- 29464903
TI  - Erratum: Adiposity and Reproductive Cycling Status in Zoo African Elephants.

PMID- 29464902
TI  - Mechanomyographic responses for the biceps brachii are associated with failure
      times during isometric force tasks.
AB  - In order to characterize the physiological adjustments within the neuromuscular
      system that contribute to task failure, this study examined the surface
      mechanomyographic (MMG) response during maximal and submaximal isometric force
      tasks of the elbow flexors sustained to failure. The time and frequency
      components of the MMG signal have shown to be influenced by motor unit activation
      patterns as well as tetanus. Therefore, it was hypothesized that the rate of
      change for the MMG response would associate with failure times and would be
      reduced to a similar degree between the two tasks. The isometric force tasks were
      performed by the dominant elbow flexors of twenty healthy males (age: 25 +/- 4
      years) and MMG was collected from the biceps brachii. Regression analyses were
      used to model the relationships between the rates of change for MMG versus
      failure times. There were high levels of interindividual variability in the
      response patterns, yet the models demonstrated significant negative associations
      between the rate of change for the MMG responses and failure times during both
      tasks (R2  = 0.41-0.72, P < 0.05). Similarly, the mean MMG amplitude and
      frequency values were reduced to comparable levels at the failure point of the
      two tasks. The results of this study demonstrated that force failure is
      associated with the rate of diminution in the properties of the muscle force
      twitch.

PMID- 29464904
TI  - Genetics of Obesity in Consanguineous Populations: Toward Precision Medicine and
      the Discovery of Novel Obesity Genes.
AB  - OBJECTIVE: Consanguinity has been instrumental in the elucidation of many
      Mendelian genetic diseases. Here, the unique advantage of consanguineous
      populations was considered in the quest for genes causing obesity. METHODS:
      PubMed was searched for articles relevant to consanguinity and obesity published
      between 1995 and 2016. Some earlier articles of interest were also consulted.
      RESULTS: Although obesity is the most heritable disorder, even in outbred
      populations, only 2% to 5% of severe obesity cases have so far been proven to be
      caused by single gene mutations. In some highly consanguineous populations, a
      remarkably higher proportion of obesity cases because of known and novel
      monogenic variants has been identified (up to 30%). CONCLUSIONS: Combining the
      power conferred by consanguinity with current large-capacity sequencing
      techniques should bring new genetic factors and molecular mechanisms to the fore,
      unveiling a large part of the yet-elusive neurohumoral circuitry involved in the
      regulation of energy homeostasis and appetite. Importantly, the undertaking of
      such initiatives is destined to unfold novel targets for the development of
      precision medicine relevant to different forms of obesity.

PMID- 29464906
TI  - Interventions During Pregnancy Reduce Excessive Gestational Weight Gain but Yield
      Unexpected Effects on Neonatal Body Composition.

PMID- 29464905
TI  - Greater Neonatal Fat-Free Mass and Similar Fat Mass Following a Randomized Trial
      to Control Excess Gestational Weight Gain.
AB  - OBJECTIVE: The objective of this study was to determine the effectiveness of
      controlling maternal gestational weight gain (GWG) in the second and third
      trimesters on neonate body composition. METHODS: Two hundred ten healthy women
      with overweight (25 > BMI < 30) or obesity (BMI >= 30) were randomly assigned to
      a lifestyle intervention (LI) program focused on controlling GWG through
      nutrition and activity behaviors or to usual obstetrical care (UC). Infant fat
      and fat-free mass (FFM) at birth were measured by using air displacement
      plethysmography (PEA POD) and by using quantitative magnetic resonance (QMR).
      RESULTS: At baseline, there were no between-group differences in maternal
      characteristics (mean [SD]): age: 33.8 (4.3) years, weight: 81.9 (13.7) kg, BMI:
      30.4 (4.5), and gestational age at randomization: 14.9 (0.8) weeks. GWG was less
      in the LI group by 1.79 kg (P = 0.003) or 0.0501 kg/wk (P = 0.002). Compared with
      UC infants, LI infants had greater weight (131 +/- 59 g P = 0.03), FFM (98 +/- 45
      g; P = 0.03) measured by PEA POD, and lean mass (105 +/- 38 g; P = 0.006)
      measured by QMR. Fat mass and percent fat were not significantly different.
      CONCLUSIONS: Intervening in women with overweight and obesity through behaviors
      promoting healthy diet and physical activity to control GWG resulted in neonates
      with similar fat and greater FFM.

PMID- 29464907
TI  - Weight Control Program and Gestational Weight Gain in Disadvantaged Women with
      Overweight or Obesity: A Randomized Clinical Trial.
AB  - OBJECTIVE: This study aimed to evaluate the efficacy of a home-based lifestyle
      intervention delivered through Parents as Teachers (PAT) to reduce excessive
      gestational weight gain (GWG). METHODS: This was a single-blinded randomized
      controlled trial conducted as part of the LIFE-Moms consortium at a single
      university-based tertiary care institution from October 2012 to March 2016. There
      were 267 socioeconomically disadvantaged (SED) African American women with
      overweight or obesity (BMI 25.0-45.0 kg/m2 before pregnancy. Participants were
      randomized to therapy with standard PAT alone (n = 134) or PAT plus a lifestyle
      intervention program embedded within the standard PAT program (PAT+) (n = 133).
      Both interventions were delivered in 10 biweekly home visits during pregnancy.
      The primary outcome was the percentage of women whose GWG exceeded the Institute
      of Medicine guidelines, and secondary outcomes included both weekly and total
      GWG. RESULTS: Compared with the standard PAT group in the intent-to-treat
      analysis, the PAT + group gained less weekly (0.4 kg vs. 0.5 kg/wk; P = 0.04) and
      total (8.0 kg vs. 9.6 kg; P = 0.02) weight during gestation. Fewer participants
      in the PAT + group had excessive total GWG (36.1% vs. 45.9%), but the difference
      between groups was not statistically significant (P = 0.11). CONCLUSIONS: PAT +
      reduced the weekly and total GWG in SED African American women with overweight or
      obesity at the start of pregnancy.

PMID- 29464909
TI  - It's Complicated: Why Raters' BMI Poorly Explained Attractiveness Ratings.

PMID- 29464908
TI  - Beauty and the Body of the Beholder: Raters' BMI Has Only Limited Association
      with Ratings of Attractiveness of the Opposite Sex.
AB  - OBJECTIVE: Assortative mating for adiposity increases the genetic burden on
      offspring, but its causes remain unclear. One hypothesis is that people who have
      high adiposity find other people with obesity more physically attractive than
      lean people. METHODS: The attractiveness of sets of images of males and females
      who varied in adiposity were rated by opposite sex subjects (559 males and 340
      females) across 12 countries. RESULTS: There was tremendous individual
      variability in attractiveness ratings. For female attractiveness, most males
      favored the leanest subjects, but others favored intermediate fatness, some were
      indifferent to body composition, and others rated the subjects with obesity as
      most attractive. For male images rated by females, the patterns were more
      complex. Most females favored subjects with low levels of adiposity (but not the
      lowest level), whereas others were indifferent to body fatness or rated the
      images depicting individuals with obesity as the most attractive. These patterns
      were unrelated to rater BMI. Among Caucasian males who rated the images of the
      thinnest females as being more attractive, the magnitude of the effect depended
      on rater BMI, indicating limited "mutual attraction." CONCLUSIONS: Individual
      variations in ratings of physical attractiveness were broadly unrelated to rater
      BMI and suggest that mutual attraction is an unlikely explanation for assortative
      mating for obesity.

PMID- 29464910
TI  - Weighing in on Bariatric Surgery: Effectiveness Among Medicaid Beneficiaries
      Limited Evidence and Future Research Needs.
AB  - INTRODUCTION: In the general population, bariatric surgery is well documented as
      the most effective obesity treatment for sustained weight loss and remission of
      comorbidities. Characterization of the patient populations most likely to benefit
      from surgical intervention is needed, but the heterogeneity of treatment effects
      across payer groups has not been reviewed. METHODS: A systematic review of
      published studies focusing on bariatric surgery outcomes among Medicaid
      beneficiaries was conducted. By using PubMed and Scopus, this study searched for
      studies that quantitatively compared clinical or social bariatric surgery
      outcomes for United States adult Medicaid recipients and commercially insured
      patients. RESULTS: Of the 568 titles reviewed, 21 met inclusion criteria. Weight
      loss and the remission of comorbidities at 1 or 2 years postoperatively were
      similar between groups despite differences in baseline health status. Short-term
      health care utilization and mortality outcomes were worse in Medicaid recipients;
      for instance, Medicaid patients had an average length of stay that was 2 days
      longer and experienced three more deaths in the first postoperative year.
      CONCLUSIONS: The critical research gaps in the evidence base needed to improve
      treatment guidelines for Medicaid patients undergoing bariatric surgery include
      an understanding of the causes of the baseline health differences and how these
      differences contribute to postoperative outcomes.

PMID- 29464912
TI  - BMX-001, a novel redox-active metalloporphyrin, improves islet function and
      engraftment in a murine transplant model.
AB  - Islet transplantation has become a well-established therapy for select patients
      with type 1 diabetes. Viability and engraftment can be compromised by the
      generation of oxidative stress encountered during isolation and culture. We
      evaluated whether the administration of BMX-001 (MnTnBuOE-2-PyP5+ [Mn(III) meso
      tetrakis-(N-b-butoxyethylpyridinium-2-yl)porphyrin]) and its earlier derivative,
      BMX-010 (MnTE-2-PyP [Mn(III) meso-tetrakis-(N-methylpyridinium-2-yl)porphyrin])
      could improve islet function and engraftment outcomes. Long-term culture of human
      islets with BMX-001, but not BMX-010, exhibited preserved in vitro viability.
      Murine islets isolated and cultured for 24 hours with 34 MUmol/L BMX-001
      exhibited improved insulin secretion (n = 3 isolations, P < .05) in response to
      glucose relative to control islets. In addition, 34 MUmol/L BMX-001-supplemented
      murine islets exhibited significantly reduced apoptosis as indicated by terminal
      deoxynucleotidyl transferase dUTP nick end labeling, compared with nontreated
      control islets (P < .05). Murine syngeneic islets transplanted under the kidney
      capsule at a marginal dose of 150 islets revealed 58% of 34 MUmol/L BMX-001
      treated islet recipients became euglycemic (n = 11 of 19) compared with 19% of
      nontreated control islet recipients (n = 3 of 19, P < .05). Of murine recipients
      receiving a marginal dose of human islets cultured with 34 MUmol/L BMX-001, 92%
      (n = 12 of 13) achieved euglycemia compared with 57% of control recipients (n = 8
      of 14, P = .11). These results demonstrate that the administration of BMX-001
      enhances in vitro viability and augments murine marginal islet mass engraftment.

PMID- 29464911
TI  - CD Obesity-Prone Rats, but not Obesity-Resistant Rats, Robustly Ferment Resistant
      Starch Without Increased Weight or Fat Accretion.
AB  - OBJECTIVE: This study used CD obesity-prone (OP) and obesity-resistant (OR) rats
      to examine how weight gain and fat accretion relate to fermentation levels and
      microbiota composition after feeding resistant starch (RS). METHODS: After
      feeding OP rats and OR rats a high-fat (HF) diet for 4 weeks, rats were
      stratified into three groups: they were fed either an HF diet (group 1: HF-HF) or
      were switched to a low-fat (LF) diet (group 2: HF-LF) or an LF diet supplemented
      with 20% RS by weight for 4 weeks (group 3: HF-LFRS). Energy intake, body weight,
      fermentation variables, and microbiota composition were determined. RESULTS: In
      OP rats, RS elicited robust fermentation (increased cecal contents, short-chain
      fatty acids, and serum glucagon-like peptide 1). Total bacteria, species of the
      Bacteroidales family S24-7, and the archaean Methanobrevibacter smithii
      increased. The robust fermentation did not elicit higher weight or fat accretion
      when compared with that of control rats fed the same isocaloric diets (HF-LF +/-
      RS). In OR rats, body weight and fat accretion were also not different between HF
      LF +/- RS diets, but RS elicited minimal changes in fermentation and microbiota
      composition. CONCLUSIONS: Robust fermentation did not contribute to greater
      weight. Fermentation levels and changes in microbiota composition in response to
      dietary RS differed by obesity phenotype.

PMID- 29464913
TI  - Evaluation of nuclear chromatin using grayscale intensity and thresholded
      percentage area in liquid-based cervical cytology.
AB  - OBJECTIVES: Development of computerized image analysis techniques has opened up
      the possibility for the quantitative analysis of nuclear chromatin in pathology.
      We hypothesized that the features extracted from digital images could be used to
      determine specific cytomorphological findings for nuclear chromatin that may be
      applicable for establishing a medical diagnosis. METHODS: Three parameters were
      evaluated from nuclear chromatin images obtained from the liquid-based cervical
      cytology samples of patients with biopsy-proven high-grade squamous
      intraepithelial lesion (HGSIL), and compared between non-neoplastic squamous
      epithelia and dysplastic epithelia groups: (1) standard deviation (SD) of the
      grayscale intensity; (2) difference between the maximum and minimum grayscale
      intensity (M-M); and (3) thresholded area percentage. Each parameter was
      evaluated at the mean, mean-1SD, and mean-2SD thresholding intensity levels.
      RESULTS: Between the mean and mean-1SD levels, the thresholded nuclear chromatin
      pattern was most similar to the chromatin granularity of the unthresholded
      grayscale images. The SD of the gray intensity and the thresholded area
      percentage differed significantly between the non-neoplastic squamous epithelia
      and dysplastic epithelia of HGSIL images at all three thresholding intensity
      levels (mean, mean-1SD, and mean-2SD). However, the M-M significantly differed
      between the two sample types for only two of the thresholding intensity levels
      (mean-1SD and mean-2SD). CONCLUSIONS: The digital parameters SD and M-M of the
      grayscale intensity, along with the thresholded area percentage could be useful
      in automated cytological evaluations. Further studies are needed to identify more
      valuable parameters for clinical application.

PMID- 29464915
TI  - Glucose uptake evaluated by 18F-fluorodeoxyglucose positron emission tomography
      in noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

PMID- 29464914
TI  - Clinical impact of ulceration width, lymphovascular invasion, microscopic
      satellitosis, perineural invasion, and mitotic rate in patients undergoing
      sentinel lymph node biopsy for cutaneous melanoma: a retrospective observational
      study at a comprehensive cancer center.
AB  - The prognostic significance of the width of the ulceration in primary melanomas
      remains unclear, and there is a relative paucity of data for lymphovascular
      invasion (LVI), microscopic satellitosis (MS), perineural invasion (PNI), and
      mitotic rate when compared with other pathological elements currently required
      for reporting. To evaluate the prognostic importance of the ulceration width and
      other important pathologic measurements, a single-institutional retrospective
      study was conducted using records of cutaneous melanoma patients who underwent
      sentinel lymph node (SLN) biopsy at The University of Texas, MD Anderson Cancer
      Center between 2003 and 2008. We identified 1898 eligible patients with median
      tumor thickness of 1.25 mm and median follow-up of 6.7 years. By multivariable
      analyses, the strongest risk factor for SLN positivity was high tumor thickness
      followed by the presence of LVI. The pathologic measures with the strongest
      influence on recurrence-free survival (RFS) were tumor thickness and positive SLN
      status. Ulceration width and presence of MS were also significantly associated
      with RFS while PNI was not. Factors with the strongest influence on melanoma
      specific survival (MSS) were positive SLN status and mitotic rate. In conclusion,
      SLN biopsy should probably be offered if the primary tumor has LVI. MS is an
      adverse prognostic factor for RFS, but its influence on outcome is modest.
      Ulceration width predicts RFS but loses its independent prognostic significance
      for MSS when adjusting for currently used clinicopathological factors. In view of
      its impact on MSS, mitotic rate should be recorded for cutaneous invasive
      melanomas across all T categories.

PMID- 29464916
TI  - Prevalence of skin tears in the extremities in inpatients at a hospital in
      Denmark.
AB  - The aims of the study were to determine the prevalence of skin tears in the
      extremities and to explore factors associated with development of skin tears in
      inpatients at a Danish hospital. The study was designed as a point prevalence
      survey and included 202 patients in the age range 19-99 (mean: 70.7, SD: 16.5).
      The patients were assessed for presence of skin tears, numbers, locations and
      previous skin tears. Data were collected using a data collection sheet developed
      for a previous study. The survey team consisted of four specialist nurses. Data
      were collected over a period of 24 hours spread over 3 days. Of the 202 patients,
      23 had skin tears, yielding a prevalence of 11.4%. In total, 40 skin tears were
      observed. Multiple logistic regression analysis showed that previous skin tears
      (odds ratio (OR): 9.3, 95% confidence interval (CI): 2.6-33.4, P < 0.001),
      ecchymosis (OR: 5.6, CI: 1.4-23.2, P < 0.017) and risk of falling (OR: 3.8, CI:
      1.2-12.0, P < 0.021) were significantly associated with development of skin
      tears. The prevalence of skin tears in this study (11.4%) matches other
      international observations. The following risk factors were recognised: previous
      skin tear, ecchymosis and risk of falling. These factors could be used to
      identify patients requiring prevention of skin tears.

PMID- 29464917
TI  - Head-to-head comparison of the heart rate variability between the bisoprolol
      transdermal patch and bisoprolol fumarate tablet.
AB  - AIM: The bisoprolol transdermal patch is a newly developed beta-blocker designed
      to deliver its pharmaceutical ingredient through the skin surface. We aimed to
      compare the bisoprolol transdermal patch and bisoprolol fumarate tablet using the
      heart rate variability (HRV). METHOD: Eligible hypertensive patients received a 2
      week administration with a 2.5 mg bisoprolol fumarate tablet, followed by 24-hour
      Holter monitoring. The tablet was then switched to a 4 mg bisoprolol transdermal
      patch, and after 2 weeks of its administration, the Holter monitoring was
      repeated. Both drugs were given once daily. Endpoint was any alteration in the
      HRV caused by a change in the administration route for bisoprolol. RESULTS: There
      was no difference in the 24-hour time-domain and frequency-domain HRV
      measurements before and after the drug switching among patients recruited (N =
      30). However, the switching significantly altered the time-course curves of the
      hourly HRV measurements, including the mean normal-to-normal (NN) interval (P =
      .004), standard deviation of the NN index (P < .001), high frequency component (P
      = .01), and low frequency component (P = .003). Those alternations were
      attributed to the slower heart rate and more decreased short-term autonomic
      fluctuation resulting from the administration of the bisoprolol transdermal
      patch, which were observed later than 12 hours after the drug initiation. No
      adverse events were noted throughout the study period. CONCLUSION: The pattern of
      the autonomic modulation may vary depending on either a transdermal or oral
      administration even though an equivalent dose of bisoprolol is given.

PMID- 29464918
TI  - Measuring Socioeconomic Status and Environmental Factors in the SAYCARE Study in
      South America: Reliability of the Methods.
AB  - OBJECTIVE: This paper aimed to test the reliability of two questionnaires in
      studies involving children and adolescents (aged 3-18 years) in seven South
      American cities. One assesses socioeconomic status (SES) and the other measures
      environmental factors. METHODS: The SES questionnaire was composed of 14
      questions, which included the presence of several consumer goods, domestic
      services, family income, parental education level, and current parental
      occupation status. The environmental questionnaire was composed of 15 questions
      to measure the social and infrastructure characteristics of the area of
      residence. Parents or guardians completed the questionnaires on behalf of their
      children. Adolescents answered the questions themselves for environmental
      factors, while those related to SES factors were answered by their parents or
      guardians. We analyzed the reliability of the questionnaires through kappa
      coefficient determination. Multilevel linear regression models were applied to
      calculate the correlation between the total household scores, the household
      income, and parents' education level. RESULTS: The environmental questionnaire
      showed good reproducibility in both age groups (k = 0.132-0.612 in children and k
      = 0.392-0.746 in adolescents). The SES questionnaire showed strong reliability in
      both age groups for all indicators (k = 0.52-1.00 in children and k = 0.296-0.964
      in adolescents). CONCLUSIONS: Our multiple indicator questionnaires focused on
      environmental factors and SES in pediatric health surveys provided useful and
      easily applicable additional indicators to measure these important determinants
      of cardiovascular health.

PMID- 29464919
TI  - Is the Measurement of Blood Pressure by Automatic Monitor in the South American
      Pediatric Population Accurate? SAYCARE Study.
AB  - OBJECTIVE: This study aimed to test the validity of an automatic oscillometric
      device to measure the blood pressure (BP) in children (n = 191) and adolescents
      (n = 127) aged 3 to 18 years. METHODS: Systolic BP (SBP) and diastolic BP (DBP)
      levels were measured simultaneous by automatic device and mercury column with Y
      connection. To verify the validity, Bland-Altman plots and limits of agreement of
      95% (95% LOA), specificity and sensitivity of the device, and the grade of
      British Hypertension Society (BHS) criteria were used. RESULTS: The monitor
      measurements demonstrated lower measurement bias (mean difference [95% LOA]): 1.4
      (-9.9 to 12.8) mmHg in children and 4.3 (-7.8 to 16.5) mmHg in adolescents for
      SBP. For DBP, it was 2.2 (-7.4 to 11.7) mmHg in children and 1.4 (-8.4 to 11.1)
      mmHg in adolescents. The sensitivity in children was 21.4 (95% CI = 16.3-26.6),
      and in adolescents, it was 20.0 (95% CI = 13.2-26.8); the specificity was 95.9
      (95% CI = 93.4-98.4) in children and 100.0 (95% CI = 100.0-100.0) in adolescents.
      The monitor-tested ratings are Grade B for SBP in children and SBP and DBP in
      adolescents and Grade C for DBP in children. CONCLUSIONS: The automatic monitor
      presented high values of specificity and lower values of sensitivity to the
      diagnosis of HBP; however, it can be considered accurate (lower measurement bias)
      and valid for epidemiological and clinical practice in accordance with BHS
      criteria.

PMID- 29464920
TI  - Development of a Food Frequency Questionnaire for Assessing Dietary Intake in
      Children and Adolescents in South America.
AB  - OBJECTIVE: This study aimed to describe the development of a food frequency
      questionnaire (FFQ) to assess dietary intake in South American children and
      adolescents. METHODS: A total of 345 children (aged 3-10 years) and 357
      adolescents (aged 11-17 years) were included for analysis. The FFQ was designed
      to be self-administered and to assess dietary intake over the past 3 months. It
      was developed in Spanish and translated into Portuguese. Multiple approaches were
      considered to compile the food list, and 11 food groups were included. A food
      photo booklet was produced as supporting material. RESULTS: The FFQ items
      maintained a common core list among centers (47 items) and country-specific
      foods. The FFQ for Buenos Aires and Lima had a total of 63 items; there were 55
      items for the FFQ in Medelin, 60 items for Montevideo, 58 items for Santiago, 67
      items for Sao Paulo, and 68 items for Teresina. Alcohol was also incorporated in
      the adolescents' FFQ. CONCLUSIONS: We developed a semiquantitative, culturally
      adapted FFQ to assess dietary intake in children and adolescents in South
      America. It has an optimal size allowing its completion in a high proportion of
      the population; therefore, it can be used in epidemiological studies with South
      American children and adolescents.

PMID- 29464921
TI  - Design and Objectives of the South American Youth/Child Cardiovascular and
      Environmental (SAYCARE) Study.
AB  - OBJECTIVE: The purpose of this paper is to introduce the overarching study design
      of the South American Youth/Child Cardiovascular and Environmental (SAYCARE)
      study, which is an observational multicenter feasibility study held in seven
      South American cities: Buenos Aires (Argentina), Lima (Peru), Medellin
      (Colombia), Montevideo (Uruguay), Santiago (Chile), and Sao Paulo and Teresina
      (Brazil). Children and adolescents (3-17 years of age) were studied. METHODS: The
      data management systems, quality assurance monitoring activities, standardized
      operating procedure manuals, and training and study management are addressed in
      this paper. Various quality controls to ensure the collection of valid and
      reliable data are also discussed. RESULTS AND CONCLUSIONS: Data were obtained
      from 237 preschoolers and schoolchildren and 258 adolescents during the
      validation phase measurements. The results of the SAYCARE study are expected to
      provide higher accuracy in the assessment of cardiovascular disease risk factors,
      including eating behaviors, body composition, physical activity, sedentary
      behaviors, lipid profiles and cardiovascular health biomarkers, oral health,
      social conditions, environmental factors and home environment, and their
      determinants in children and adolescents from ages 3 to 17 in seven South
      American cities.

PMID- 29464922
TI  - Reliability and Validity of a Questionnaire for Physical Activity Assessment in
      South American Children and Adolescents: The SAYCARE Study.
AB  - OBJECTIVE: The objective of this article is to test the reliability and validity
      of the new and innovative physical activity (PA) questionnaire. METHODS:
      Subsamples from the South American Youth/Child Cardiovascular and Environment
      Study (SAYCARE) study were included to examine its reliability (children: n =
      161; adolescents: n = 177) and validity (children: n = 82; adolescents: n = 60).
      The questionnaire consists of three dimensions of PA (leisure, active commuting,
      and school) performed during the last week. To assess its validity, the subjects
      wore accelerometers for at least 3 days and 8 h/d (at least one weekend day). The
      reliability was analyzed by correlation coefficients. In addition, Bland-Altman
      analysis and a multilevel regression were applied to estimate the measurement
      bias, limits of agreement, and influence of contextual variables. RESULTS: In
      children, the questionnaire showed consistent reliability (rho = 0.56) and
      moderate validity (rho = 0.46), and the contextual variable variance explained
      43.0% with -22.9 min/d bias. In adolescents, the reliability was higher (rho =
      0.76) and the validity was almost excellent (rho = 0.88), with 66.7% of the
      variance explained by city level with 16.0 min/d PA bias. CONCLUSIONS: The
      SAYCARE PA questionnaire shows acceptable (in children) to strong (in
      adolescents) reliability and strong validity in the measurement of PA in the
      pediatric population from low- to middle-income countries.

PMID- 29464923
TI  - Effect of acute hypoxemia on cerebral blood flow velocity control during lower
      body negative pressure.
AB  - The ability to maintain adequate cerebral blood flow and oxygenation determines
      tolerance to central hypovolemia. We tested the hypothesis that acute hypoxemia
      during simulated blood loss in humans would cause impairments in cerebral blood
      flow control. Ten healthy subjects (32 +/- 6 years, BMI 27 +/- 2 kg.m-2 ) were
      exposed to stepwise lower body negative pressure (LBNP, 5 min at 0, -15, -30, and
      -45 mmHg) during both normoxia and hypoxia (Fi O2  = 0.12-0.15 O2 titrated to an
      SaO2 of ~85%). Physiological responses during both protocols were expressed as
      absolute changes from baseline, one subject was excluded from analysis due to
      presyncope during the first stage of LBNP during hypoxia. LBNP induced greater
      reductions in mean arterial pressure during hypoxia versus normoxia (MAP, at -45
      mmHg: -20 +/- 3 vs. -5 +/- 3 mmHg, P < 0.01). Despite differences in MAP, middle
      cerebral artery velocity responses (MCAv) were similar between protocols (P =
      0.41) due to increased cerebrovascular conductance index (CVCi) during hypoxia
      (main effect, P = 0.04). Low frequency MAP (at -45 mmHg: 17 +/- 5 vs. 0 +/- 5
      mmHg2 , P = 0.01) and MCAv (at -45 mmHg: 4 +/- 2 vs. -1 +/- 1 cm.s-2 , P = 0.04)
      spectral power density, as well as low frequency MAP-mean MCAv transfer function
      gain (at -30 mmHg: 0.09 +/- 0.06 vs. -0.07 +/- 0.06 cm.s-1 .mmHg-1 , P = 0.04)
      increased more during hypoxia versus normoxia. Contrary to our hypothesis, these
      findings support the notion that cerebral blood flow control is not impaired
      during exposure to acute hypoxia and progressive central hypovolemia despite
      lower MAP as a result of compensated increases in cerebral conductance and flow
      variability.

PMID- 29464924
TI  - Development of a novel affinity chromatography resin for platform purification of
      bispecific antibodies with modified protein a binding avidity.
AB  - There is strong interest in the production of bispecific monoclonal antibodies
      that can simultaneously bind two distinct targets or epitopes to achieve novel
      mechanisms of action and efficacy. Regeneron's bispecific technology, based upon
      a standard IgG, consists of a heterodimer of two different heavy chains, and a
      common light chain. Coexpression of two heavy chains leads to the formation of
      two parental IgG impurities, the removal of which is facilitated by a dipeptide
      substitution in the Fc portion of one of the heavy chains that ablates Fc Protein
      A binding. Therefore, the affinity capture (Protein A) step of the purification
      process must perform both bulk capture and high resolution of these mAb
      impurities, a task current commercially available resins are not designed for.
      Resolution can be further impaired by the ability of Protein A to bind some
      antibodies in the variable region of the heavy chain (VH ). This article details
      development of a novel Protein A resin. This resin combines an alkali stable
      ligand with a base matrix exhibiting excellent mass transfer properties to allow
      high capacity single step capture and resolution of bispecific antibodies (bsAbs)
      with high yields. The developed resin, named MabSelect SuReTM pcc, is implemented
      in GMP production processes for several bsAbs. (c) 2018 The Authors Biotechnology
      Progress published by Wiley Periodicals, Inc. on behalf of American Institute of
      Chemical Engineers Biotechnol. Prog., 34:650-658, 2018.

PMID- 29464925
TI  - Molecular characterization of unusual bovine rotavirus A strains having high
      genetic relatedness with human rotavirus: evidence for zooanthroponotic
      transmission.
AB  - We report here the genomic characterization of two rare rotavirus A (RVAs)
      G1P[11] and G9P[X] strains detected in cattle calves from two different
      geographical locations in India during routine rotavirus surveillance. These
      strains possessed unusual G types (VP7 gene) on a bovine/artiodactyl genotype
      constellation, G1-P[11]-I2-Rx-Cx-Mx-Ax-N2-T6-E2-H3 (HR-B91) and G9-P[X]-I2-Rx-Cx
      Mx-Ax-N2-T6-E2-H3 (WB-H2). This is the first report on molecular characterization
      of G9 in cattle, and second report on G1 in cattle. The VP7 gene of HR-B91
      occupied lineage IIc within G1 while that of WB-H2 occupied IIIb within G9
      genotype. The latter was found to be very diverse from other RVA strains of G9
      genotype, and this may emerge as a new genotype in due course. The study provides
      evidence of zooanthroponotic transmission of human G1 and G9 RVA genes to calves.
      Of note, the G9 genotype was found to serve as the ancestral genotype for G1.
      Phylogenetic analysis of remaining gene segments revealed close relatedness to
      artiodactyl or artiodactyl-like human RVA strains. The findings of this study
      highlight the potential role of interspecies transmission and reassortment events
      in generating the rare rotavirus strains.

PMID- 29464926
TI  - Expression of miR-634 in gastric carcinoma and its effects on proliferation,
      migration, and invasion of gastric cancer cells.
AB  - This study aims to observe the expression of microRNA (miR)-634 in different
      gastric cancer cell lines and tissues, and to study the effects of miR-634 on the
      proliferation, migration, and invasion of the gastric cancer cells. The miR-634
      mimics and miR-634 inhibitors were transfected by lentivirus into human gastric
      cancer SGC-7901 and MGC-803 cells, and the miR-634 cells without transfection
      were used as the control group (NC group). The expression of miR-634 in the
      transfected cells was detected by qRT-PCR. Cell viability was measured by the
      CCK8 assay. The migration and invasion ability of the cells were detected by
      scratch assays and Transwell(r) chamber assays, respectively, and the luciferase
      assay verified the binding of miR-634 to the target gene JAG1. The expression
      level of miR-634 in gastric cancer tissues and cell lines was significantly lower
      than that in normal adjacent tissues and control cells. The survival of cells was
      significantly decreased, and number of cells migrating and invading was decreased
      in the miR-634 mimics group. However, in the miR-634 inhibitor group, the
      opposite results were observed. Over-expression of miR-634 inhibited the
      proliferation, migration, and invasion of gastric cancer cell lines, and the miR
      634 target gene was JAG1.

PMID- 29464927
TI  - Microbial lipid extraction from Lipomyces starkeyi using irreversible
      electroporation.
AB  - The aim of the study was to investigate the feasibility of using irreversible
      electroporation (EP) as a microbial cell disruption technique to extract
      intracellular lipid within short time and in an eco-friendly manner. An EP
      circuit was designed and fabricated to obtain 4 kV with frequency of 100 Hz of
      square waves. The yeast cells of Lipomyces starkeyi (L. starkeyi) were treated by
      EP for 2-10 min where the distance between electrodes was maintained at 2, 4, and
      6 cm. Colony forming units (CFU) were counted to observe the cell viability under
      the high voltage electric field. The forces of the pulsing electric field caused
      significant damage to the cell wall of L. starkeyi and the disruption of
      microbial cells was visualized by field emission scanning electron microscopic
      (FESEM) image. After breaking the cell wall, lipid was extracted and measured to
      assess the efficiency of EP over other techniques. The extent of cell
      inactivation was up to 95% when the electrodes were placed at the distance of 2
      cm, which provided high treatment intensity (36.7 kWh m-3 ). At this condition,
      maximum lipid (63 mg g-1 ) was extracted when the biomass was treated for 10 min.
      During the comparison, EP could extract 31.88% lipid while the amount was 11.89%
      for ultrasonic and 16.8% for Fenton's reagent. The results recommend that the EP
      is a promising technique for lowering the time and solvent usage for lipid
      extraction from microbial biomass. (c) 2018 American Institute of Chemical
      Engineers Biotechnol. Prog., 34:838-845, 2018.

PMID- 29464928
TI  - Metabolic responses and pathway changes of mammalian cells under different
      culture conditions with media supplementations.
AB  - Amino acids and glucose consumption, cell growth and monoclonal antibody (mAb)
      production in mammalian cell culture are key considerations during upstream
      process and particularly media optimization. Understanding the interrelations and
      the relevant cellular physiology will provide insight for setting strategy of
      robust and effective mAb production. The aim of this study was to further our
      understanding of nutrient consumption metabolism, since this could have
      significant impact on enhancing mAb titer, cell proliferation, designing feeding
      strategies, and development of feed media. The nutrient consumption pattern, mAb
      concentration, and cell growth were analyzed in three sets of cell cultures with
      media supplementation of glucose, methionine, threonine, tryptophan, and
      tyrosine. The amino acids metabolism and its impact on cell growth and mAb
      production during the batch and fed-batch culture were closely analyzed. It was
      shown that the phenylalanine, tyrosine and tryptophan biosynthesis pathways were
      significantly altered under different culture conditions with different media.
      These changes were more apparent in the fed-batch process in which higher mAb
      titer was observed due to the metabolic changes than mAb titer in the batch
      process. The pathway analysis approach was well utilized for evaluating the
      impact on the relevant pathways involved under different cell culture conditions
      to improve cell growth and mAb titer. (c) 2018 American Institute of Chemical
      Engineers Biotechnol. Prog., 34:793-805, 2018.

PMID- 29464929
TI  - Distinct signal transductions in fast- and slow- twitch muscles upon denervation.
AB  - Denervation induces skeletal muscle atrophy, which primarily impairs oxidative
      slow twitch fibers. The underlying mechanism of this phenomenon, however, remains
      to be addressed. We hypothesize that denervation-induced fiber-specific atrophy
      may result from the distinct activities of different signaling pathways that are
      involved in protein synthesis and degradation in fast- and slow-twitch fibers. In
      this study, 1-month-old male mice were subjected to unilateral sciatic
      denervation for 4 days. Fast-twitch muscle extensor digitorum longus (EDL) and
      slow-twitch muscle soleus were collected from the denervated side and the control
      side of hind limbs. Total and phosphorylated protein levels of key factors of
      major signaling pathways in these tissues were determined using western blot
      assay. Our data showed that total AKT and FoxO3 protein levels were upregulated
      in denervated muscles as compared with control sides. Phosphorylation of AKT and
      FoxO3 were proportionally enhanced in denervated EDL but not soleus, indicating
      AKT activation drives phosphorylation of FoxO3 in EDL but not in soleus upon
      denervation. As a result, FoxO3-targeted atrogenes MurF1 and Atrogin1 protein
      abundances were reduced in denervated EDL but not altered in soleus. In
      consistent with this change, polyubiquitination were significantly increased in
      denervated soleus, but only a slight increase in ubiquitination was found in
      denervated EDL. Autophagy marker LC3 protein level was significantly increased in
      both muscle types, but in greater extent in EDL after denervation. IRS1 protein
      level and active ERK were reduced in both muscles upon denervation, which might
      contribute to the upregulation of total AKT protein level and FoxO3 abundance in
      EDL and soleus. Total and phosphorylated AMPK protein levels were increased in
      denervated soleus but not in EDL. Overall, these data reveal that the key
      signaling pathways that regulate protein synthesis and degradation are more
      sensitive in soleus than EDL in response to denervation.

PMID- 29464930
TI  - Cytology of hydatid cyst mimicking intra-abdominal sarcoma, diagnosed by fine
      needle aspiration.

PMID- 29464931
TI  - New FIG4 gene mutations causing aggressive ALS.

PMID- 29464932
TI  - Predictors of response to onabotulinumtoxin A in chronic migraine.

PMID- 29464933
TI  - Corrigendum.

PMID- 29464934
TI  - Long-term educational program to limit the burden of neurological disorders in
      Sub-Saharan Africa: report from an Italy-Mozambique cooperation on epilepsy in
      children.

PMID- 29464936
TI  - Evaluation of cellular adhesion and organization in different microporous
      polymeric scaffolds.
AB  - The lack of prediction accuracy during drug development and screening risks
      complications during human trials, such as drug-induced liver injury (DILI), and
      has led to a demand for robust, human cell-based, in vitro assays for drug
      discovery. Microporous polymer-based scaffolds offer an alternative to the gold
      standard flat tissue culture plastic (2D TCPS) and other 3D cell culture
      platforms as the porous material entraps cells, making it advantageous for
      automated liquid handlers and high-throughput screening (HTS). In this study, we
      optimized the surface treatment, pore size, and choice of scaffold material with
      respect to cellular adhesion, tissue organization, and expression of complex
      physiologically relevant (CPR) outcomes such as the presence of bile canaliculi
      like structures. Poly-l-lysine and fibronectin (FN) coatings have been shown to
      encourage cell attachment to the underlying substrate. Treatment of the scaffold
      surface with NaOH followed with a coating of FN improved cell attachment and
      penetration into pores. Of the two pore sizes we investigated (A: 104 +/- 4 MUm;
      B: 175 +/- 6 MUm), the larger pore size better promoted cell penetration while
      limiting tissue growth from reaching the hypoxia threshold. Finally, polystyrene
      (PS) proved to be conducive to cell growth, penetration into the scaffold, and
      yielded CPR outcomes while being a cost-effective choice for HTS applications.
      These observations provide a foundation for optimizing microporous polymer-based
      scaffolds suitable for drug discovery. (c) 2018 American Institute of Chemical
      Engineers Biotechnol. Prog., 34:505-514, 2018.

PMID- 29464937
TI  - Vascular dysfunction elicited by a cross talk between periaortic adipose tissue
      and the vascular wall is reversed by pioglitazone.
AB  - AIM: Perivascular adipose tissue (PVAT) is in intimate contact with the vessel
      wall and extravascular PVAT-derived inflammatory mediators may adversely
      influence atherosclerotic plaque formation and stability through outside-to
      inside signaling. We sought to investigate the role of PVAT on the atheroma
      development in an experimental animal model of metabolic syndrome (MS) associated
      with oxidative stress and low-grade inflammatory state. We also studied the
      effect of pioglitazone an insulin sensitizer, on the aortic wall and its
      surrounding PVAT, considering a bi-directional communication between both layers.
      METHODS: Apolipoprotein E-deficient mice (ApoE-/- ) were fed with standard diet
      (CD, control diet) or fructose overload (10% w/v) (FD, fructose diet) for 8 weeks
      and treated with or without pioglitazone the latest 4 weeks. RESULTS: Biochemical
      variables show that glycemia and lipid peroxidation determined by thiobarbituric
      acid reactive species (TBARS) significantly increased in FD-fed ApoE-/- mice. FD
      significantly increased aortic PVAT expression of oxidative stress associated
      genes: p22phox , Nox1, Nox2, Nox4 and p47phox , and proinflammatory genes:
      Visfatin, MCP-1, and MMP-9. Pioglitazone diminished PVAT-oxidative damage
      elicited by fructose treatment and markedly down-regulated proinflammatory
      markers. Even pioglitazone did not prevent the development of the aortic atheroma
      plaques stimulated by FD, significantly diminished VCAM-1 expression, MMP-9
      expression and activity in aortic media wall and significantly reduced the
      accumulation of lipids and macrophages in atheroma plaques. CONCLUSION: Our
      results support the fact that PVAT contributes to the development and progression
      of cardiovascular disease by underlying mechanisms elicited by "outside-in"
      signaling. Treatment with pioglitazone may offer a new effect on the whole vessel
      wall, promoting the stability of advanced atherosclerotic plaques.

PMID- 29464938
TI  - Reliability of maximal mitochondrial oxidative phosphorylation in permeabilized
      fibers from the vastus lateralis employing high-resolution respirometry.
AB  - The purpose was to assess the impact of various factors on methodological errors
      associated with measurement of maximal oxidative phosphorylation (OXPHOS) in
      human skeletal muscle determined by high-resolution respirometry in saponin
      permeabilized fibers. Biopsies were collected from 25 men to assess differences
      in OXPHOS between two muscle bundles and to assess the correlation between OXPHOS
      and the wet weight of the muscle bundle. Biopsies from left and right thighs of
      another five subjects were collected on two occasions to compare limbs and time
      points. A single muscle specimen was used to assess effects of the anesthetic
      carbocaine and the influence of technician. The difference in OXPHOS between two
      fiber-bundles from the same biopsy exhibited a standard error of measurement
      (SEM) of 10.5 pmol . s-1  . mg-1 and a coefficient of variation (CV) of 15.2%.
      The differences between left and right thighs and between two different time
      points had SEMs of 9.4 and 15.2 pmol . s-1  . mg-1 and CVs of 23.9% and 33.1%,
      respectively. The average (+/-SD) values obtained by two technicians monitoring
      different bundles of fibers from the same biopsy were 31.3 +/- 7.1 and 26.3 +/-
      8.1 pmol . s-1  . mg-1 . The time that elapsed after collection of the biopsy (up
      to a least 5 h in preservation medium), wet weight of the bundle (from 0.5 to 4.5
      mg) and presence of an anesthetic did not influence OXPHOS. The major source of
      variation in OXPHOS measurements is the sample preparation. The thigh involved,
      time-point of collection, size of fiber bundles, and time that elapsed after
      biopsy had minor or no effect.

PMID- 29464939
TI  - Genome analysis of two novel Pseudomonas strains exhibiting differential
      hypersensitivity reactions on tobacco seedlings reveals differences in
      nonflagellar T3SS organization and predicted effector proteins.
AB  - Multilocus sequence analysis (MLSA) of two new biological control strains (S1E40
      and S3E12) of Pseudomonas was performed to assess their taxonomic position
      relative to close lineages, and comparative genomics employed to investigate
      whether these strains differ in key genetic features involved in hypersensitivity
      responses (HRs). Strain S3E12, at high concentration, incites HRs on tobacco and
      corn plantlets while S1E40 does not. Phylogenies based on individual genes and
      16S rRNA-gyrB-rpoB-rpoD concatenated sequence data show strains S1E40 and S3E12
      clustering in distinct groups. Strain S3E12 consistently clustered with
      Pseudomonas marginalis, a bacterium causing soft rots on plant tissues. MLSA data
      suggest that strains S1E40 and S3E12 are novel genotypes. This is consistent with
      the data of genome-based DNA-DNA homology values that are below the proposed
      cutoff species boundary. Comparative genomics analysis of the two strains
      revealed major differences in the type III secretion systems (T3SS) as well as
      the predicted T3SS secreted effector proteins (T3Es). One nonflagellar (NF-T3SS)
      and two flagellar T3SSs (F-T3SS) clusters were identified in both strains. While
      F-T3SS clusters in both strains were relatively conserved, the NF-T3SS clusters
      differed in the number of core components present. The predicted T3Es also
      differed in the type and number of CDSs with both strains having unique predicted
      protease-related effectors. In addition, the T1SS organization of the S3E12
      genome has protein-coding sequences (CDSs) encoding for key factors such as T1SS
      secreted agglutinin repeats-toxins (a group of cytolysins and cytotoxins), a
      membrane fusion protein (LapC), a T1SS ATPase of LssB family (LapB), and T1SS
      associated transglutaminase-like cysteine proteinase (LapP). In contrast, strain
      S1E40 has all CDSs for the seven-gene operon (pelA-pelG) required for Pel
      biosynthesis but not S3E12, suggesting that biofilm formation in these strains is
      modulated differently. The data presented here provide an insight of the genome
      organization of these two phytobacterial strains.

PMID- 29464941
TI  - Laparoscopic versus abdominal myomectomy: trend and pattern of practice among
      reproductive age population in Kedah, Malaysia.

PMID- 29464942
TI  - Flexible Hydrophobic Antifouling Coating with Oriented Nanotopography and
      Nonleaking Capsaicin.
AB  - Incorporating natural product antifoulants (NPAs) into coatings with controlled
      surface topography is considered a promising way to suppress marine fouling.
      However, the rapid leakage of NPAs and the relatively complicated process of
      constructing well-patterned topography remain unresolved problems for practical
      applications. In this work, capsaicin bonded to CoFe2O4/gelatin magnetic
      nanoparticles was mixed with a polydimethylsiloxane (PDMS)-based block copolymer.
      When applied together by a simple spray-coating method, these materials formed a
      film. The leakage of capsaicin was restrained by the chemical bonds with the
      CoFe2O4/gelatin nanospheres. The primary nanorough structure was constructed by
      the phase separation of the PDMS-based copolymer. The secondary nanorough
      structure was formed by the incorporation of capsaicin-loaded CoFe2O4/gelatin
      nanospheres, which were demonstrated to improve the orientation of the PDMS-based
      block copolymer chains. The combination of oriented nanotopography and nonleaking
      capsaicin endows the coating with enhanced, long-lasting antifouling ability.

PMID- 29464943
TI  - Molecular Profiling of Pooled Circulating Tumor Cells from Prostate Cancer
      Patients Using a Dual-Antibody-Functionalized Microfluidic Device.
AB  - To capture both epithelial and mesenchymal subpopulations of CTCs at different
      metastatic stages of PCa patients, here we constructed a novel dual-antibody
      functionalized microfluidic device by employing antibodies against PSMA and
      EpCAM. In vitro experiments with the dual capture system for capturing both LnCAP
      and LnCAP-EMT cells have shown significantly enhanced capture efficiency as
      compared to that of the EpCAM single capture system. Furthermore, the dual
      capture system could successfully identify CTCs in 20 out of 24 (83.3%) PCa
      patients, and the CTCs counts from the dual capture system were statistically
      correlated with the TNM stage of patients ( P < 0.05), while conventional
      diagnostic methods, such as serum PSA level and Gleason score, failed to
      correlate to patient TNM stages. To further explore potential clinical
      application of our dual capture system, captured CTCs were recovered and
      subjected to qRT-PCR to quantify known factors involved in PCa development and
      therapy. The results demonstrated that the combined detection of SChLAP1 and PSA
      in CTCs is a potential marker for identifying patients with metastatic PCa, while
      detection of AR and PD-L1 in CTCs may have the potential to determine the
      sensitivity of PCa patients to androgen deprivation therapy and immunotherapy,
      respectively. Taken together, the dual-antibody-functionalized microfluidic
      device established in our study overcomes the limitations of some CTC capture
      platforms that only detect epithelial or mesenchymal CTCs in PCa patients, and
      detection of the PCa-related RNA signatures from purified CTCs holds great
      promise to offer warnings for early metastasis of PCa and may provide guidance
      for therapy decisions.

PMID- 29464940
TI  - Multiplatform plasma fingerprinting in cancer cachexia: a pilot observational and
      translational study.
AB  - BACKGROUND: Cachexia is a metabolic syndrome that affects up to 50-80% of cancer
      patients. The pathophysiology is characterized by a variable combination of
      reduced food intake and abnormal metabolism, including systemic inflammation and
      negative protein and energy balance. Despite its high clinical significance,
      defined diagnostic criteria and established therapeutic strategies are lacking.
      The 'omics' technologies provide a global view of biological systems. We
      hypothesize that blood-based metabolomics might identify findings in cachectic
      patients that could provide clues to gain knowledge on its pathophysiology, and
      eventually postulate new therapeutic strategies. METHODS: This is a cross
      sectional observational study in two cohorts of cancer patients, with and without
      cachexia. Patients were consecutively recruited from routine clinical practice of
      a General Oncology Department at '12 de Octubre' University Hospital. Selected
      clinical and biochemical features were collected. Blood metabolite fingerprinting
      was performed using three analytical platforms, gas chromatography coupled to
      mass spectrometry (GC-MS), capillary electrophoresis coupled to mass spectrometry
      (CE-MS), and liquid chromatography coupled to mass spectrometry (LC-MS). Besides,
      we performed pathway-based metabolite analyses to obtain more information on
      biological functions. RESULTS: A total of 15 subjects were included in this
      study, 8 cachectic and 7 non-cachectic patients. Metabolomic analyses were able
      to correctly classify their samples in 80% (GC-MS), 97% (CE-MS), 96% [LC-MS
      (positive mode)], and 89% [LC-MS (negative mode)] of the cases. The most
      prominent metabolic alteration in plasma of cachectic patients was the decrease
      of amino acids and derivatives [especially arginine, tryptophan, indolelactic
      acid, and threonine, with 0.4-fold change (FC) compared with non-cachectic
      patients], along with the reduction of glycerophospholipids [mainly
      lysophosphatidylcholines(O-16:0) and lysophosphatidylcholines(20:3) sn-1, FC =
      0.1] and sphingolipids [SM(d30:0), FC = 0.5]. The metabolite with the highest
      increase was cortisol (FC = 1.6). Such alterations suggest a role of the
      following metabolic pathways in the pathophysiology of cancer cachexia: arginine
      and proline metabolism; alanine, aspartate, and glutamate metabolism;
      phenylalanine metabolism; lysine degradation; aminoacyl-tRNA biosynthesis; fatty
      acid elongation in mitochondria; tricarboxylic acids cycle; among others.
      CONCLUSIONS: These findings suggest that plasma amino acids and lipids profiling
      has great potential to find the mechanisms involved in the pathogenesis of
      cachexia. Metabolic profiling of plasma from cancer patients show differences
      between cachexia and non-cachexia in amino acids and lipids that might be related
      to mechanisms involved in its pathophysiology. A better understanding of these
      mechanisms might identify novel therapeutic approaches to palliate this unmet
      medical condition.

PMID- 29464944
TI  - Ultralow Power Consumption Flexible Biomemristors.
AB  - Low power consumption is the important requirement in memory devices for saving
      energy. In particular, improved energy efficiency is essential in implantable
      electronic devices for operation under a limited power supply. Here, we
      demonstrate the use of kappa-carrageenan (kappa-car) as the resistive switching
      layer to achieve memory that has low power consumption. A carboxymethyl (CM)
      group is introduced to the kappa-car to increase its ionic conductivity. Ag was
      doped in CM:kappa-car to improve the resistive switching properties of the
      devices. Memory devices based on Ag-doped CM:kappa-car showed electroforming-free
      resistive switching. This device exhibited low reset voltage (~0.05 V), fast
      switching speed (50 ns), and high on/off ratio (>103) under low compliance
      current (10-5 A). Its power consumption (~0.35 MUW) is much lower than those of
      the previously reported biomemristors. The resistive switching may be a result of
      an electrochemical redox process and Ag filament formation in the CM:kappa-car
      under an electric field. This biopolymer memory can also be fabricated on
      flexible substrate. This study verifies the feasibility of using biopolymers for
      applications to future implantable and biocompatible nanoelectronics.

PMID- 29464945
TI  - Synthesis and Evaluation of Antimicrobial and Antibiofilm Properties of A-Type
      Procyanidin Analogues against Resistant Bacteria in Food.
AB  - Natural A-type procyanidins have shown very interesting biological activities,
      such as their proven antiadherence properties against pathogenic bacteria. In
      order to find the structural features responsible for their activities, we
      describe herein the design and synthesis of six A-type procyanidin analogues and
      the evaluation of their antimicrobial and antibiofilm properties against 12
      resistant bacteria, both Gram positive and Gram negative, isolated from organic
      foods. The natural A-type procyanidin A-2, which had known antiadherence
      activity, was also tested as a reference compound for the comparative studies.
      Within the series, analogue 4, which had a NO2 group on ring A, showed the
      highest antimicrobial activity (MIC of 10 MUg/mL) and was one of the best
      molecules at preventing biofilm formation (up to 40% decreases at 100 MUg/mL) and
      disrupting preformed biofilms (up to 40% reductions at 0.1 MUg/mL). Structure
      activity relationships are also analyzed.

PMID- 29464946
TI  - Uptake of TiO2 Nanoparticles into C. elegans Neurons Negatively Affects Axonal
      Growth and Worm Locomotion Behavior.
AB  - We employ model organism Caenorhabditis elegans to effectively study the
      toxicology of anatase and rutile phase titanium dioxide (TiO2) nanoparticles
      (NPs). The experimental results show that nematode C. elegans can take up
      fluorescein isothiocyanate-labeled TiO2 NPs and that both anatase and rutile TiO2
      NPs can be detected in the cytoplasm of cultured primary neurons imaged by
      transmission electron microscopy. After TiO2 NP exposure, these neurons also grow
      shorter axons, which may be related to the detected impeded worm locomotion
      behavior. Furthermore, anatase TiO2 NPs did not affect the worm's body length;
      however, we determined that a concentration of 500 MUg/mL of anatase TiO2 NPs
      reduced the worm population by 50% within 72 h. Notably, rutile TiO2 NPs
      negatively affect both the body size and worm population. Worms unable to enter
      the L4 larval stage explain a severe reduction in the worm population at TiO2 NPs
      LC50/3d. To obtain a better understanding of the cellular mechanisms involved in
      TiO2 NP intoxication, DNA microarray assays were employed to determine changes in
      gene expression in the presence or absence of TiO2 NP exposure. Our data reveal
      that three genes (with significant changes in expression levels) were related to
      metal binding or metal detoxification (mtl-2, C45B2.2, and nhr-247), six genes
      were involved in fertility and reproduction (mtl-2, F26F2.3, ZK970.7, clec-70,
      K08C9.7, and C38C3.7), four genes were involved in worm growth and body
      morphogenesis (mtl-2, F26F2.3, C38C3.7, and nhr-247), and five genes were
      involved in neuronal function (C41G6.13, C45B2.2, srr-6, K08C9.7, and C38C3.7).

PMID- 29464947
TI  - Interfacial Strength and Surface Damage Characteristics of Atomically Thin h-BN,
      MoS2, and Graphene.
AB  - Surface damage characteristics of single- and multilayer hexagonal boron nitride
      (h-BN), molybdenum disulfide (MoS2), and graphene films were systematically
      investigated via atomic force microscopy (AFM)-based progressive-force and
      constant-force scratch tests and Raman spectroscopy. The film-to-substrate
      interfacial strengths of these atomically thin films were assessed based on their
      critical forces (i.e., the normal force where the atomically thin film was
      delaminated from the underlying substrate), as determined from progressive-force
      scratch tests. The evolution of surface damage with respect to normal force was
      further investigated using constant-force tests. The results showed that single
      layer h-BN, MoS2, and graphene strongly adhere to the SiO2 substrate, which
      significantly improves its tribological performance. Moreover, defect formation
      induced by scratch testing was found to affect the topography and friction force
      differently prior to failure, which points to distinct surface damage
      characteristics. Interestingly, the residual strains at scratched areas suggest
      that the scratch test-induced in-plane compressive strains were dominant over
      tensile strains, thereby leading to buckling in front of the scratching tip and
      eventually failure at sufficient strains. These trends represent the general
      failure mechanisms of atomically thin materials because of a scratch test. As the
      number of layers increased, the tribological performances of atomically thin h
      BN, MoS2, and graphene were found to significantly improve because of an increase
      in the interfacial strengths and a decrease in the surface damage and friction
      force. In all, the findings on the distinctive surface damage characteristics and
      general failure mechanisms are useful for the design of reliable, protective and
      solid-lubricant coating layers based on these materials for nanoscale devices.

PMID- 29464948
TI  - Inhibition of Oral Pathogens Adhesion to Human Gingival Fibroblasts by Wine
      Polyphenols Alone and in Combination with an Oral Probiotic.
AB  - Several benefits have been described for red wine polyphenols and probiotic
      strains in the promotion of colonic metabolism and health. On the contrary,
      knowledge about their role in the management of oral health is still scarce. In
      this work, the antiadhesive capacity of selected red wine polyphenols and
      oenological extracts against the oral pathogens Porphyromonas gingivalis,
      Fusobacterium nucleatum, and Streptococcus mutans in an in vitro model of human
      gingival fibroblasts has been explored as well as their complementary action with
      the candidate oral probiotic Streptococcus dentisani. Results highlighted the
      antiadhesive capacity of caffeic and p-coumaric acids as well as grape seed and
      red wine oenological extracts. Both, caffeic and p-coumaric acids increased their
      inhibition potential against S. mutans adhesion when combined with S. dentisani.
      Additionally, UHPLC-MS/MS analysis demonstrated the oral metabolism of wine
      phenolics due to both, cellular and bacterial activity.

PMID- 29464949
TI  - Field Application of 238U/235U Measurements To Detect Reoxidation and
      Mobilization of U(IV).
AB  - Biostimulation to induce reduction of soluble U(VI) to relatively immobile U(IV)
      is an effective strategy for decreasing aqueous U(VI) concentrations in
      contaminated groundwater systems. If oxidation of U(IV) occurs following the
      biostimulation phase, U(VI) concentrations increase, challenging the long-term
      effectiveness of this technique. However, detecting U(IV) oxidation through
      dissolved U concentrations alone can prove difficult in locations with few
      groundwater wells to track the addition of U to a mass of groundwater. We propose
      the 238U/235U ratio of aqueous U as an independent, reliable tracer of U(IV)
      remobilization via oxidation or mobilization of colloids. Reduction of U(VI)
      produces 238U-enriched U(IV), whereas remobilization of solid U(IV) should not
      induce isotopic fractionation. The incorporation of remobilized U(IV) with a high
      238U/235U ratio into the aqueous U(VI) pool produces an increase in 238U/235U of
      aqueous U(VI). During several injections of nitrate to induce U(IV) oxidation,
      238U/235U consistently increased, suggesting 238U/235U is broadly applicable for
      detecting mobilization of U(IV).

PMID- 29464950
TI  - Microcapsules Containing pH-Responsive, Fluorescent Polymer-Integrated MoS2: An
      Effective Platform for in Situ pH Sensing and Photothermal Heating.
AB  - We report the design of a novel microcapsule platform for in situ pH sensing and
      photothermal heating, which involves the encapsulation of pH-responsive polymer
      coated molybdenum disulfide (MoS2) nanosheets (NSs) in microcapsules with an
      aqueous core and a semipermeable polymeric shell. The MoS2 NSs were
      functionalized with pH-responsive polymers having fluorescent groups at the
      distal end to provide pH-sensitive Forster resonance energy transfer (FRET)
      effect. The pH-responsive polymers were carefully designed to produce a dramatic
      change in the polymer conformation, which translated to a change in the FRET
      efficiency near pH 7.0 in response to subtle pH changes, enabling the detection
      of cancer cells. The pH-sensitive MoS2 NSs were microfluidically encapsulated
      within semipermeable membranes to yield microcapsules with a uniform size and
      composition. The microcapsules retained the MoS2 NSs without leakage while
      allowing the diffusion of small ions and water through the membrane. At the same
      time, the membranes excluded adhesive proteins and lipids in the surrounding
      media, protecting the encapsulated MoS2 NSs from deactivation and enabling in
      situ pH monitoring. Moreover, the encapsulated MoS2 NSs showed high-performance
      photothermal heating, rendering the dual-functional microcapsules highly suitable
      for cancer diagnosis and treatment.

PMID- 29464951
TI  - Ferroelectricity in Hf0.5Zr0.5O2 Thin Films: A Microscopic Study of the
      Polarization Switching Phenomenon and Field-Induced Phase Transformations.
AB  - Because of their full compatibility with the modern Si-based technology, the HfO2
      based ferroelectric films have recently emerged as viable candidates for
      application in nonvolatile memory devices. However, despite significant efforts,
      the mechanism of the polarization switching in this material is still under
      debate. In this work, we elucidate the microscopic nature of the polarization
      switching process in functional Hf0.5Zr0.5O2-based ferroelectric capacitors
      during its operation. In particular, the static domain structure and its
      switching dynamics following the application of the external electric field have
      been monitored with the advanced piezoresponse force microscopy (PFM) technique
      providing a nm resolution. Separate domains with strong built-in electric field
      have been found. Piezoresponse mapping of pristine Hf0.5Zr0.5O2 films revealed
      the mixture of polar phase grains and regions with low piezoresponse as well as
      the continuum of polarization orientations in the grains of polar orthorhombic
      phase. PFM data combined with the structural analysis of pristine versus trained
      film by plan-view transmission electron microscopy both speak in support of a
      monoclinic-to-orthorhombic phase transition in ferroelectric Hf0.5Zr0.5O2 layer
      during the wake-up process under an electrical stress.

PMID- 29464952
TI  - High-Content Screening of Plankton Alkaline Phosphatase Activity in
      Microfluidics.
AB  - One way for phytoplankton to survive orthophosphate depletion is to utilize
      dissolved organic phosphorus by expressing alkaline phosphatase. The actual
      methods to assay alkaline phosphate activity-either in bulk or as a
      presence/absence of enzyme activity-fail to provide information on individual
      living cells. In this context, we develop a new microfluidic method to
      compartmentalize cells in 0.5 nL water-in-oil droplets and measure alkaline
      phosphatase activity at the single-cell level. We use enzyme-labeled fluorescence
      (ELF), which is based on the hydrolysis of ELF-P substrate, to monitor in real
      time and at the single-cell level both qualitative and quantitative information
      on cell physiology (i.e., localization and number of active enzyme sites and
      alkaline phosphatase kinetics). We assay the alkaline phosphatase activity of
      Tetraselmis sp. as a function of the dissolved inorganic phosphorus concentration
      and show that the time scale of the kinetics spans 1 order of magnitude. The
      advantages of subnanoliter-scale compartmentalization in droplet-based
      microfluidics provide a precise characterization of a population with single-cell
      resolution. Our results highlight the key role of cell physiology to efficiently
      access dissolved organic phosphorus.

PMID- 29464953
TI  - Infrared Population Transfer Spectroscopy of Cryo-Cooled Ions: Quantitative Tests
      of the Effects of Collisional Cooling on the Room Temperature Conformer
      Populations.
AB  - The single-conformation spectroscopy and infrared-induced conformational
      isomerization of a model protonated pentapeptide [YGPAA + H]+ is studied under
      cryo-cooled conditions in the gas phase. Building on recent results ( DeBlase ,
      A. F. ; J. Am. Chem. Soc. 2017 , 139 , 5481 - 5493 ), firm assignments are
      established for the presence of two conformer families with distinct infrared and
      ultraviolet spectra, using IR-UV depletion spectroscopy. Families (A and B) share
      a similar structure near the N-terminus but differ in the way that the C-terminal
      COOH group configures itself (cis versus trans) in forming H-bonds with the
      peptide backbone. Infrared population transfer (IR-PT) spectroscopy is used to
      study the IR-induced conformational isomerization following single-conformer
      infrared excitation. IR-induced isomerization is accomplished in both directions
      (A -> B and B -> A) in the hydride stretch region and is used to determine
      fractional abundances for the two conformer families (FA = 0.65 +/- 0.04, FB =
      0.35 +/- 0.04, 2sigma error bars). The time scale for collisional cooling of the
      room-temperature ions to Tvib = 10 K by cold helium in the octupole trap is
      established as 1.0 ms. Key stationary points on the isomerization potential
      energy surface are calculated at the DFT B3LYP/6-31+G(d) G3DBJ level of theory.
      Using RRKM theory, the energy-dependent isomerization rates and populations are
      calculated as a function of energy. According to the model, the observed
      population distribution after collisional cooling is close to that of the 298 K
      Boltzmann distribution and is in near-quantitative agreement with experiment. On
      the basis of this success, inferences are drawn for the circumstances that govern
      the population distribution in the trap, concluding that, in ions the size of
      [YGPAA + H]+ and larger, the observed distributions will be near those at 298 K.

PMID- 29464954
TI  - Ultrafast, Self-Driven, and Air-Stable Photodetectors Based on Multilayer
      PtSe2/Perovskite Heterojunctions.
AB  - We report on the large-scale synthesis of polycrystalline multilayer PtSe2 film
      with typical semimetallic characteristics. With the availability of the large
      area film, we constructed a heterojunction composed of multilayer PtSe2 and Cs
      doped FAPbI3, which can function as a self-driven photodetector in a broadband
      wavelength from the ultraviolet to the near-infrared region. Further
      photoresponse analysis revealed that the heterojunction device showed outstanding
      photosensitive characteristics with a large Ilight/ Idark ratio of 5.7 * 103,
      high responsivity of 117.7 mA W-1, and decent specific detectivity of 2.91 * 1012
      Jones at zero bias. More importantly, the rise/fall times were estimated to be
      78/60 ns, rendering our device the fastest device among perovskite-2D
      photodetectors reported to date. In addition, it was also observed that the
      PtSe2/perovskite photodetector can almost retain its photoresponse properties
      after storage in ambient conditions for 3 weeks. This study suggests the
      potential of the present PtSe2/perovskite heterojunction for future air-stable
      ultrafast photodetecting applications.

PMID- 29464955
TI  - The Interplay Between Hydrogen Bonding and Coulombic Forces in Determining the
      Structure of Sulfuric Acid-Amine Clusters.
AB  - Acid-base cluster chemistry drives atmospheric new particle formation (NPF), but
      the details of the growth mechanisms are difficult to experimentally probe.
      Clusters of ammonia, alkylamines, and sulfuric acid, species fundamental to NPF,
      are probed by infrared spectroscopy. These spectra show that substitution of
      amines for ammonia, which is linked to accelerated growth, induces profound
      structural rearrangement in clusters with initial compositions (NH4+) n+1(HSO4-)
      n (1 <= n <= 3). This rearrangement is driven by the loss of N-H hydrogen bond
      donors, yielding direct bisulfate-bisulfate hydrogen bonds, and its onset with
      respect to cluster composition indicates that more substituted amines induce
      rearrangement at smaller sizes. A simple model counting hydrogen bond donors and
      acceptors explains these observations. The presence of direct hydrogen bonds
      between formal anions shows that hydrogen bonding can compete with Coulombic
      forces in determining cluster structure. These results suggest that NPF
      mechanisms may be highly dependent on amine identity.

PMID- 29464956
TI  - Characterization of Indole-3-acetic Acid Biosynthesis and the Effects of This
      Phytohormone on the Proteome of the Plant-Associated Microbe Pantoea sp. YR343.
AB  - Indole-3-acetic acid (IAA) plays a central role in plant growth and development,
      and many plant-associated microbes produce IAA using tryptophan as the precursor.
      Using genomic analyses, we predicted that Pantoea sp. YR343, a microbe isolated
      from Populus deltoides, synthesizes IAA using the indole-3-pyruvate (IPA)
      pathway. To better understand IAA biosynthesis and the effects of IAA exposure on
      cell physiology, we characterized proteomes of Pantoea sp. YR343 grown in the
      presence of tryptophan or IAA. Exposure to IAA resulted in upregulation of
      proteins predicted to function in carbohydrate and amino acid transport and
      exopolysaccharide (EPS) biosynthesis. Metabolite profiles of wild-type cells
      showed the production of IPA, IAA, and tryptophol, consistent with an active IPA
      pathway. Finally, we constructed an Delta ipdC mutant that showed the elimination
      of tryptophol, consistent with a loss of IpdC activity, but was still able to
      produce IAA (20% of wild-type levels). Although we failed to detect intermediates
      from other known IAA biosynthetic pathways, this result suggests the possibility
      of an alternate pathway or the production of IAA by a nonenzymatic route in
      Pantoea sp. YR343. The Delta ipdC mutant was able to efficiently colonize poplar,
      suggesting that an active IPA pathway is not required for plant association.

PMID- 29464958
TI  - sp-d Exchange Interactions in Wave Function Engineered Colloidal CdSe/Mn:CdS
      Hetero-Nanoplatelets.
AB  - In two-dimensional (2D) colloidal semiconductor nanoplatelets, which are
      atomically flat nanocrystals, the precise control of thickness and composition on
      the atomic scale allows for the synthesis of heterostructures with well-defined
      electron and hole wave function distributions. Introducing transition metal
      dopants with a monolayer precision enables tailored magnetic exchange
      interactions between dopants and band states. Here, we use the absorption based
      technique of magnetic circular dichroism (MCD) to directly prove the exchange
      coupling of magnetic dopants with the band charge carriers in hetero
      nanoplatelets with CdSe core and manganese-doped CdS shell (CdSe/Mn:CdS). We show
      that the strength of both the electron as well as the hole exchange interactions
      with the dopants can be tuned by varying the nanoplatelets architecture with
      monolayer accuracy. As MCD is highly sensitive for excitonic resonances, excited
      level spectroscopy allows us to resolve and identify, in combination with wave
      function calculations, several excited state transitions including spin-orbit
      split-off excitonic contributions. Thus, our study not only demonstrates the
      possibility to expand the extraordinary physical properties of colloidal
      nanoplatelets toward magneto-optical functionality by transition metal doping but
      also provides an insight into the excited state electronic structure in this
      novel two-dimensional material.

PMID- 29464957
TI  - Development of a Unified Enantioselective, Convergent Synthetic Approach Toward
      the Furanobutenolide-Derived Polycyclic Norcembranoid Diterpenes: Asymmetric
      Formation of the Polycyclic Norditerpenoid Carbocyclic Core by Tandem Annulation
      Cascade.
AB  - An enantioselective and diastereoselective approach toward the synthesis of the
      tetracyclic scaffold of the furanobutenolide-derived polycyclic norditerpenoids
      is described. Focusing on synthetic efforts toward ineleganolide, the synthetic
      approach utilizes a palladium-catalyzed enantioselective allylic alkylation for
      the construction of the requisite chiral tertiary ether. A diastereoselective
      cyclopropanation-Cope rearrangement cascade enabled the convergent assembly of
      the ineleganolide [6,7,5,5]-tetracyclic scaffold. Investigation of substrates for
      this critical tandem annulation process is discussed along with synthetic
      manipulations of the [6,7,5,5]-tetracyclic scaffold and the attempted
      interconversion of the [6,7,5,5]-tetracyclic scaffold of ineleganolide to the
      isomeric [7,6,5,5]-core of scabrolide A and its naturally occurring isomers.
      Computational evaluation of ground-state energies of late-stage synthetic
      intermediates was used to guide synthetic development and aid in the
      investigation of the conformational rigidity of these highly constrained and
      compact polycyclic structures.

PMID- 29464959
TI  - Angstrom-Size Defect Creation and Ionic Transport through Pores in Single-Layer
      MoS2.
AB  - Atomic-defect engineering in thin membranes provides opportunities for ionic and
      molecular filtration and analysis. While molecular-dynamics (MD) calculations
      have been used to model conductance through atomic vacancies, corresponding
      experiments are lacking. We create sub-nanometer vacancies in suspended single
      layer molybdenum disulfide (MoS2) via Ga+ ion irradiation, producing membranes
      containing ~300 to 1200 pores with average and maximum diameters of ~0.5 and ~1
      nm, respectively. Vacancies exhibit missing Mo and S atoms, as shown by
      aberration-corrected scanning transmission electron microscopy (AC-STEM). The
      longitudinal acoustic band and defect-related photoluminescence were observed in
      Raman and photoluminescence spectroscopy, respectively. As the irradiation dose
      is increased, the median vacancy area remains roughly constant, while the number
      of vacancies (pores) increases. Ionic current versus voltage is nonlinear and
      conductance is comparable to that of ~1 nm diameter single MoS2 pores, proving
      that the smaller pores in the distribution display negligible conductance.
      Consistently, MD simulations show that pores with diameters <0.6 nm are almost
      impermeable to ionic flow. Atomic pore structure and geometry, studied by AC
      STEM, are critical in the sub-nanometer regime in which the pores are not
      circular and the diameter is not well-defined. This study lays the foundation for
      future experiments to probe transport in large distributions of angstrom-size
      pores.

PMID- 29464960
TI  - Composition-Dependent Energy Splitting between Bright and Dark Excitons in Lead
      Halide Perovskite Nanocrystals.
AB  - Perovskite semiconductor nanocrystals with different compositions have shown
      promise for applications in light-emitting devices. Dark excitonic states may
      suppress light emission from such nanocrystals by providing an additional
      nonradiative recombination channel. Here, we study the composition dependence of
      dark exciton dynamics in nanocrystals of lead halides by time-resolved
      photoluminescence spectroscopy at cryogenic temperatures. The presence of a spin
      related dark state is revealed by magneto-optical spectroscopy. The energy
      splitting between bright and dark states is found to be highly sensitive to both
      halide elements and organic cations, which is explained by considering the
      effects of size confinement and charge screening, respectively, on the exchange
      interaction. These findings suggest the possibility of manipulating dark exciton
      dynamics in perovskite semiconductor nanocrystals by composition engineering,
      which will be instrumental in the design of highly efficient light-emitting
      devices.

PMID- 29464961
TI  - Spatially Resolved Lateral Transmission Measurements to Characterize Changes in
      the Scattering Coefficient and the Anisotropy Factor.
AB  - A new setup is described to characterize the scattering coefficient and the
      scattering phase function of liquid media. The setup utilizes the basic idea of a
      spatially resolved reflectance measurement combined with a sophisticated
      illumination geometry. The sample is illuminated parallel and close to the
      interface of the sample and a glass window to get information from single
      scattered and multiple scattered light. By illuminating the sample with a fiber
      orientated with the axis parallel to the glass surface, small distances to the
      source can be examined unimpeded by the illumination beam. The derived
      information is, for example, not only sensitive to the concentration of the
      scatterers but also to the size of the scattering particles. We present the setup
      including the theory to describe the light propagation in the whole configuration
      using Monte Carlo simulations. The validation has been done with polystyrene
      microsphere dispersions with different scattering coefficients. As application
      for the developed setup, we show measurements of different milk samples which
      vary in concentration of fat, protein, and in fat droplet size during
      homogenization process. By measuring milk, we show the ability of the sensor to
      determine information about the scattering phase function without diluting the
      sample. For sensors in the dairy industry, a measurement with no pre-processing
      and no diluting of the sample is worthwhile, because this can be used to
      determine the fat and protein concentration on-line.

PMID- 29464962
TI  - Antifungal activity of fluconazole-loaded natural rubber latex against Candida
      albicans.
AB  - AIM: This work aimed to produce a membrane based on fluconazole-loaded natural
      rubber latex (NRL), and study their interaction, drug release and antifungal
      susceptibility against Candida albicans. MATERIALS & METHODS: Fluconazole-loaded
      NRL membrane was obtained by casting method. RESULTS: The Fourier Transform
      Infrared Spectroscopy showed no modifications either in NRL or fluconazole after
      the incorporation. Mechanical test presented low Young's modulus and high strain,
      indicating the membranes have sufficient elasticity for biomedical application.
      The bio-membrane was able to release the drug and inhibit the growth of C.
      albicans as demonstrated by disk diffusion and macrodilution assays. CONCLUSION:
      The biomembrane was able to release fluconazole and inhibit the growth of C.
      albicans, representing a promising biomaterial for skin application.

PMID- 29464963
TI  - Cognitive inflexibility in a young woman with pyromania.
AB  - Background Pyromania is a rare disorder that is characterized by multiple
      episodes of deliberate and purposeful fire-setting. It is typically associated
      with significant psychosocial dysfunction and legal problems. Even so, little
      research has examined cognitive aspects of the disorder. Case presentation/study
      In this study, we compared a 24-year-old woman with pyromania with 19 age- and
      gender-matched healthy controls using a battery of computerized neurocognitive
      tasks. Our participant affected by pyromania showed impaired cognitive
      flexibility but intact functioning on measures of impulsive action and decision
      making. Discussion Although pyromania shares phenomenological similarities with
      other urge-driven disorders, our results suggest that pyromania may have features
      of compulsivity as well. Conclusions Pyromania is relatively understudied from a
      neurobiological perspective. Further research is needed to understand the
      pathophysiology, classification, and treatment of pyromania.

PMID- 29464964
TI  - Nine years of comparative effectiveness research education and training:
      initiative supported by the PhRMA Foundation.
AB  - The term comparative effectiveness research (CER) took center stage with passage
      of the American Recovery and Reinvestment Act (2009). The companion US$1.1
      billion in funding prompted the launch of initiatives to train the scientific
      workforce capable of conducting and using CER. Passage of the Patient Protection
      and Affordable Care Act (2010) focused these initiatives on patients, coining the
      term 'patient-centered outcomes research' (PCOR). Educational and training
      initiatives were soon launched. This report describes the initiative of the
      Pharmaceutical Research and Manufacturers Association of America (PhRMA)
      Foundation. Through provision of grant funding to six academic Centers of
      Excellence, to spearheading and sponsoring three national conferences, the PhRMA
      Foundation has made significant contributions to creation of the scientific
      workforce that conducts and uses CER/PCOR.

PMID- 29464965
TI  - Comparative effectiveness and patient-centered outcomes research: enhancing
      uptake and use by patients, clinicians and payers.
AB  - Evidence from comparative effectiveness research (CER) and patient-centered
      outcomes research (PCOR) studies are increasingly available in the literature.
      However, there remain opportunities to better integrate that evidence into
      decision-making. An invitation-only conference held in January 2017, titled
      "Comparative Effectiveness and Patient-Centered Outcomes Research: Enhancing
      Uptake and Use by Patients, Clinicians and Payers", sought to identify and
      discuss both gaps in the uptake and use of CER/PCOR, and approaches to enhance
      the uptake and use of CER/PCOR evidence by patients, clinicians and payers. In
      this article, we summarize the conference proceedings, and highlight the themes
      and recommendations that resulted from the sessions. This paper also introduces
      other articles in this issue of CER from that conference.

PMID- 29464966
TI  - Trends in transfusion rates after the FOCUS trial.
AB  - AIM: We estimate the impact of the FOCUS trial, which concluded that hip surgery
      patients with hemoglobin values above 8 g/dl do not benefit from routine
      transfusions, on transfusion rates. METHODS: We evaluated trends in transfusion
      rates using inpatient discharge data from four states. RESULTS: The transfusion
      rate was 5.2 percentage points lower in the fourth quarter of 2013 than it would
      have been had pre-FOCUS trends continued. Transfusion rates declined more in
      hospitals with a low end-of-life treatment intensity index, a general measure of
      treatment intensity. CONCLUSION: The FOCUS trial affected practice, but there are
      additional opportunities to reduce the use of transfusions.

PMID- 29464967
TI  - The Familias Saludables partnership: Engaging the Latino community to address
      early childhood obesity.
AB  - Darcy A Thompson is an Associate Professor of pediatrics at the University of
      Colorado School of Medicine. Her main research seeks to address early childhood
      obesity in low-income children. She works in the Lifestyle Medicine clinic at
      Children's Hospital Colorado, a clinic focused on caring for children with
      obesity and related comorbidities. She is also an Associate Medical Director for
      the Research Institute at Children's Hospital Colorado. Her training includes a
      Master of Public Health degree, a medical degree (Yale University) and the Robert
      Wood Johnson Clinical Scholars Fellowship (University of Washington). Deborah
      (Deb) A Federspiel has been leading child health advocacy and community health
      improvement initiatives in support of Children's Hospital Colorado's mission for
      the past 15 years. Her professional background includes experience developing and
      managing teams, programs and operations, as well as building partnerships and
      coalitions to drive key strategic initiatives and advance positive change on
      behalf of children and families. An active member of a number of community
      advisory committees and nonprofit boards, she has worked in the Colorado
      nonprofit sector since 1999. She has a Bachelor of Science in business
      administration from the University of Dayton.

PMID- 29464968
TI  - Forecasting the size and peak of cholera epidemic in Yemen, 2017.

PMID- 29464969
TI  - Clostridioides (Clostridium) difficile infection: current and alternative
      therapeutic strategies.
AB  - Clostridioides difficile (C. difficile) has become a pathogen of worldwide
      importance considering that epidemic strains are disseminated in hospitals of
      several countries, where community-acquired infections act as a constant source
      of new C. difficile strains into hospitals. Despite the advances in the treatment
      of infections, more effective therapies against C. difficile are needed but, at
      the same time, these therapies should be less harmful to the resident
      gastrointestinal microbiota. The purpose of this review is to present a
      description of issues associated to C. difficile infection, a summary of current
      therapies and those in developmental stage, and a discussion of potential
      combinations that may lead to an increased efficacy of C. difficile infection
      treatment.

PMID- 29464970
TI  - Comparative evaluation of GeneXpert MTB/RIF and multiplex PCR targeting mpb64 and
      IS6110 for the diagnosis of pleural TB.
AB  - AIM: Diagnosis of pleural TB poses serious challenges due to paucibacillary
      nature of specimens and there is an urgent need to devise a reliable diagnostic
      test. METHODS: We compared GeneXpert Mycobacterium tuberculosis/rifampin assay
      and the multiplex PCR (M-PCR) targeting mpb64 (Rv1980c) and IS6110 in pleural
      fluids (n = 78) of pleural TB patients and non-TB controls. RESULTS: The
      sensitivities of 89.6 and 33.3%, and specificities of 96.7 and 100%, were
      observed with M-PCR and Xpert assay, respectively. CONCLUSION: M-PCR showed
      superiority over Xpert assay and may facilitate an efficient diagnosis of pleural
      TB.

PMID- 29464971
TI  - Inflammatory Nodules Identify Steroid-Responsive Primary Sclerosing Cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a cholangiopathy-usually associated with
      inflammatory bowel disease-that leads to cirrhosis and liver failure. Based on a
      multitude of clinical trials, there is general consensus that PSC progression is
      unchanged by current therapies, including steroids. However, there are scattered
      reports in the literature of PSC patients responsive to steroids. Recently,
      several steroid-responsive PSC mimics have been described, most notably
      immunoglobulin G4-related sclerosing cholangitis. Following these discoveries,
      many assume that cases in the literature previously reported as steroid
      responsive PSC would now be classified as one of these mimics. We reviewed liver
      biopsies and the medical histories of patients diagnosed with PSC with documented
      response to steroids. We identified 3 cases of steroid-responsive PSC in patients
      with inflammatory bowel disease that do not fit criteria of known PSC mimics. All
      3 were adults (age range = 18-44 years) with inflammatory bowel disease, and
      included 2 males and 1 female. All 3 patients had abnormal liver function tests
      that normalized on prednisone. Histologically, these 3 cases share a common
      feature, hepatic fibroinflammatory nodules in a collagen-rich background. They
      lacked clinical, serologic, and histologic features of immunoglobulin G4-related
      sclerosing cholangitis. These cases suggest that fibroinflammatory nodules may
      identify a unique subset of PSC patients who are responsive to steroids.

PMID- 29464972
TI  - Malignant Transformation Arising Within Unusual and Rare Hepatic Lesions:
      Fibropolycystic Disease Form of Ductal Plate Malformation and Biliary
      Adenofibroma.
AB  - Cholangiocarcinoma is the second most common hepatobiliary cancer following
      hepatocellular carcinoma, and 20% to 25% are intrahepatic. We describe 2 cases of
      intrahepatic cholangiocarcinoma arising within unusual and rare hepatic lesions,
      fibropolycystic liver disease form of ductal plate malformation and biliary
      adenofibroma, whose association with malignancy is rarely reported in the
      literature.

PMID- 29464973
TI  - Trajectories of Episodic Disability in People Aging with HIV: A Longitudinal
      Qualitative Study.
AB  - People living with HIV may experience disability which is episodic in nature,
      characterized by periods of wellness and illness. The purpose of this
      longitudinal qualitative study was to understand how the episodic nature of HIV
      and the associated uncertainty shape the disability experience of older adults
      living with HIV over time. Fourteen men and 10 women who were HIV positive and
      over 50 years (mean age: 57 years; range: 50-73) participated in 4 interviews
      over 20 months. Longitudinal analyses of the transcribed interviews identified 4
      phenotypes of episodic disability over time: decreasing, increasing, stable, or
      significant fluctuations. Although all participants experienced uncertainty,
      acceptance and optimism were hallmarks of those whose phenotypes were stable or
      improved over time. Understanding a person's episodic trajectory may help to
      tailor interventions to promote stability, mitigate an upward trajectory of
      increasing disability, and increase the time between episodes of illness.

PMID- 29464974
TI  - A Comparison of Spastic Diplegia in Term and Preterm-Born Children.
AB  - This study compared the risk factors and clinical and radiologic profile of
      children with spastic diplegic cerebral palsy born at term (>=37 weeks) with
      those born preterm. Children (2-14 years) with cerebral palsy meeting the study
      criteria for spastic diplegia were enrolled. Antecedent risk factors, clinical
      profile, and magnetic resonance imaging (MRI) findings were recorded. Spasticity,
      functional ability, intellectual ability, and social quotient were assessed using
      standard scales. Ninety-three children met the study inclusion criteria (45 term,
      48 preterm). Moderate to severe intellectual disability (53% vs 21%, P = .001)
      and epilepsy (51% vs 33%) were significantly more common in term-born children,
      whereas periventricular white matter injury was less common in term-born children
      (64%vs 89.4%, P = .004). Term spastic diplegia was associated with
      cortical/subcortical involvement in (11/42 (26%) vs 3/47(6.4%); P = .01). We
      conclude that term-spastic-diplegia is clinicopathologically different from
      preterm-spastic-diplegia. Their neuroradiologic pattern also differs with more
      frequent involvement of cortical/subcortical areas.

PMID- 29464975
TI  - Pembrolizumab and its use in the treatment of recurrent or metastatic head and
      neck cancer.
AB  - Until recently, palliative options for the treatment of platinum-refractory
      recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have
      been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited
      efficacy with substantial toxicity. The development of novel immune checkpoint
      inhibitors has challenged the standard treatment. Pembrolizumab is a potent and
      highly selective humanized monoclonal antibody that blocks the interaction
      between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2. In
      August 2016, the US FDA approved the use of pembrolizumab in R/M HNSCC following
      disease progression on or after platinum-containing chemotherapy. This review
      highlights the pharmacology, therapeutic efficacy and tolerability data relevant
      to the use of pembrolizumab for the treatment of R/M HNSCC. Readers will gain
      greater insight into the HNSCC tumor microenvironment, available biomarkers, and
      learn about important clinical considerations associated with the use of
      pembrolizumab and similar immune checkpoint inhibitors.

PMID- 29464976
TI  - Elevated levels of C-reactive protein and IL-6 among the antipsychotic medicating
      schizophrenia patients of Siliguri, West Bengal, India.
AB  - PURPOSE: Chronic, low-grade inflammation is a proposed etiological factor
      associated with schizophrenia. Thus, various studies have been conducted to
      understand the role of inflammatory process in schizophrenia by using
      inflammatory maker C-reactive protein (CRP) with conflicting findings.
      Inadvertently, studies of CRP among the Indian schizophrenia patients are very
      few. Therefore, the present study was undertaken to investigate the role of
      inflammatory process among Indian Bengalee schizophrenia patients of Siliguri,
      using the marker CRP and its stimulating cytokine interleukin-6 (IL-6). In
      addition, the study also intended to investigate the immunomodulatory effect of
      antipsychotic medication on serum levels of CRP and IL-6. MATERIALS AND METHODS:
      The serum levels of CRP and IL-6 were measured by Enzyme-Linked Immunosorbent
      Assay (ELISA) among 67 antipsychotic medicating, 28 psychotropic medication-free
      schizophrenia patients, and it was compared with 72 age, sex and ethnicity
      matched controls. RESULTS: A significantly higher level of CRP and IL-6 were
      recorded among the antipsychotic medicating patients. Although CRP was found to
      be higher among the psychotropic medication-free patients than the controls, it
      was not found to be significant. However, a significantly higher level of IL-6
      was observed in this group. CONCLUSIONS: The results provide the evidence for a
      possible immunomodulatory effect of antipsychotic drugs on CRP. Future
      investigations including the study of antipsychotics separately may help to
      understand the differential effects of individual antipsychotics on CRP level.
      Additional studies with a larger sample size of psychotropic medication-free
      patients may help to verify the role of inflammation in schizophrenia patients of
      this region.

PMID- 29464977
TI  - How combined multicomparative proteomic approaches can improve the understanding
      of quinolone resistance in Salmonella Typhimurium.

PMID- 29464978
TI  - The association between birth weight at term and long-term endocrine morbidity of
      the offspring.
AB  - OBJECTIVE: To investigate whether small-for-gestational-age (SGA) and large-for
      gestational-age (LGA) birth weight at-term poses an increased risk for long-term
      pediatric endocrine morbidity. STUDY DESIGN: A retrospective population-based
      cohort study compared the incidence of long-term pediatric hospitalizations due
      to endocrine morbidity of singleton children born SGA, appropriate-for
      gestational-age (AGA), and LGA at-term. A multivariate generalized estimating
      equation (GEE) logistic regression model analysis was used to control for
      confounders. RESULTS: During the study period, 235,614 deliveries met the
      inclusion criteria; of which 4.7% were SGA (n = 11,062), 91% were AGA (n =
      214,249), and 4.3% were LGA neonates (n = 10,303). During the follow-up period,
      children born SGA or LGA at-term had a significantly higher rate of long-term
      endocrine morbidity. Using a multivariable GEE logistic regression model,
      controlling for confounders, being delivered SGA or LGA at-term was found to be
      an independent risk factor for long-term pediatric endocrine morbidity (Adjusted
      OR = 1.4; 95%CI = 1.1-1.8; p = .015 and aOR = 1.4; 95%CI = 1.1-1.8; p = .005,
      respectively). Specifically, LGA was found an independent risk factor for
      overweight and obesity (aOR = 1.7; 95%CI = 1.2-2.5; p = .001), while SGA was
      found an independent risk factor for childhood hypothyroidism (aOR = 3.2; 95%CI =
      1.8-5.8; p = .001). CONCLUSIONS: Birth weight either SGA or LGA at-term is an
      independent risk factor for long-term pediatric endocrine morbidity.

PMID- 29464979
TI  - Erratum: Halson and Lastella (2017).
AB  - In Halson SL, Lastella M, "Amazing athletes with ordinary habits: why is changing
      behavior so difficult?" Int J Sports Physiol Perform. 2017;12(10):1273-1274,
      10.1123/ijspp.2017-0632 , the second author's first name was misspelled when
      first published in the online version only. It appeared online as Michelle
      instead of Michele, the latter of which is the correct spelling. The online
      version of the article has been corrected.

PMID- 29464980
TI  - Evaluation the efficacy of trichloroacetic acid (TCA) 33% in treatment of oral
      retinoid-induced cheilitis compared with placebo (Vaseline): a randomized pilot
      study.
AB  - BACKGROUND: Oral Isotretinoin (13-cis-retinoic acid) is a gold standardtreatment
      for severe forms of acne with cheilitis as a most frequent complication. We
      designed this novel study to investigate the therapeutic effect of
      trichloroacetic acid (TCA) 33% as compared with placebo to treat cheilitis.
      METHODS: In this pilot study, 90 acne vulgaris patients between 18 and 50 years,
      who referred dermatologic clinic with cheilitis, were assigned to either case
      (TCA) or control (Vaseline) group using permuted-block randomization from 2013 to
      2015 with data analysis in 2016. Patients had follow-up visits after 2 and 6
      weeks, at which their lesions were photographed. Two blinded expert
      dermatologists recorded physician International global score for each image.
      RESULTS: Ninety eligible patients were randomly allocated into two groups. This
      included 45 patients in each group. At the end of follow-up, 44 patients in the
      intervention group and 37 patients in control group completed the final
      assessment. Compared to the control group, the TCA group had a greater reduction
      in the mean ICGS value from baseline to Week 6 (mean difference 2.59 points, p <
      .0001). CONCLUSIONS: TCA can be considered as a good strategy in improvement of
      cheilitis to isotretinoin therapy.

PMID- 29464981
TI  - Multiple sclerosis-related fatigue: Altered resting-state functional connectivity
      of the ventral striatum and dorsolateral prefrontal cortex.
AB  - OBJECTIVE: Since recent studies suggested a role of the striatum and prefrontal
      cortex for multiple sclerosis (MS)-related fatigue, we investigated resting-state
      functional connectivity alterations of striatal subdivisions and the dorsolateral
      prefrontal cortex (dlPFC). METHODS: Resting-state functional magnetic resonance
      imaging was acquired in 77 relapsing-remitting MS patients (38 fatigued (F-MS),
      39 non-fatigued (NF-MS)) and 41 matched healthy controls (HC). Fatigue severity
      was assessed using the fatigue severity scale. Seed-based connectivity analyses
      were performed using subregions of the striatum and the dlPFC as regions of
      interest applying non-parametric permutation testing. RESULTS: Compared to HC and
      NF-MS patients, F-MS patients showed reduced caudate nucleus and ventral striatum
      functional connectivity with the sensorimotor cortex (SMC) and frontal, parietal,
      and temporal cortex regions. Fatigue severity correlated negatively with
      functional connectivity of the caudate nucleus and ventral striatum with the SMC
      and positively with functional connectivity of the dlPFC with the rostral
      inferior parietal gyrus and SMC. CONCLUSION: MS-related fatigue is associated
      with reduced functional connectivity between the striatum and sensorimotor as
      well as attention and reward networks, in which the ventral striatum might be a
      key integration hub. Together with increased connectivity between the dlPFC and
      sensory cortical areas, these connectivity alterations shed light on the
      mechanisms of MS-related fatigue.

PMID- 29464982
TI  - RCC1 regulates inner centromeric composition in a Ran-independent fashion.
AB  - RCC1 associates to chromatin dynamically within mitosis and catalyzes Ran-GTP
      production. Exogenous RCC1 disrupts kinetochore structure in Xenopus egg extracts
      (XEEs), but the molecular basis of this disruption remains unknown. We have
      investigated this question, utilizing replicated chromosomes that possess paired
      sister kinetochores. We find that exogenous RCC1 evicts a specific subset of
      inner KT proteins including Shugoshin-1 (Sgo1) and the chromosome passenger
      complex (CPC). We generated RCC1 mutants that separate its enzymatic activity and
      chromatin binding. Strikingly, Sgo1 and CPC eviction depended only on RCC1's
      chromatin affinity but not its capacity to produce Ran-GTP. RCC1 similarly
      released Sgo1 and CPC from synthetic kinetochores assembled on CENP-A nucleosome
      arrays. Together, our findings indicate RCC1 regulates kinetochores at the
      metaphase-anaphase transition through Ran-GTP-independent displacement of Sgo1
      and CPC.

PMID- 29464983
TI  - Repurposing anticancer drugs for targeting necroptosis.
AB  - Necroptosis represents a form of programmed cell death that can be engaged by
      various upstream signals, for example by ligation of death receptors, by viral
      sensors or by pattern recognition receptors. It depends on several key signaling
      proteins, including the kinases Receptor-Interacting Protein (RIP)1 and RIP3 and
      the pseudokinase mixed-lineage kinase domain-like protein (MLKL). Necroptosis has
      been implicated in a number of physiological and pathophysiological conditions
      and is disturbed in many human diseases. Thus, targeted interference with
      necroptosis signaling may offer new opportunities for the treatment of human
      diseases. Besides structure-based drug design, in recent years drug repositioning
      has emerged as a promising alternative to develop drug-like compounds. There is
      accumulating evidence showing that multi-targeting kinase inhibitors, for example
      Dabrafenib, Vemurafenib, Sorafenib, Pazopanib and Ponatinib, used for the
      treatment of cancer also display anti-necroptotic activity. This review
      summarizes recent evidence indicating that some anticancer kinase inhibitors also
      negatively affect necroptosis signaling. This implies that some cancer
      therapeutics may be repurposed for other pathologies, e.g. ischemic or
      inflammatory diseases.

PMID- 29464984
TI  - The challenges of implementing advanced access for residents in family medicine
      in Quebec. Do promising strategies exist?
AB  - BACKGROUND: The advanced access (AA) model is a highly recommended innovation to
      improve timely access to primary healthcare. Despite that many studies have shown
      positive impacts for healthcare professionals, and for patients, implementing
      this model in clinics with a teaching mission for family medicine residents poses
      specific challenges. OBJECTIVE: To identify these challenges within these
      clinics, as well as potential strategies to address them. DESIGN: The authors
      adopted a qualitative multiple case study design, collected data in 2016 using
      semi-structured interviews (N = 40) with healthcare professionals and clerical
      staff in four family medicine units in Quebec, and performed a thematic analysis.
      They validated results through a discussion workshop, involving many family
      physicians and residents practicing in different regions Results: Five challenges
      emerged from the data: 1) choosing, organizing residents' patient; 2) managing
      and balancing residents' appointment schedules; 3) balancing timely access with
      relational continuity; 4) understanding the AA model; 5) establishing
      collaborative practices with other health professionals. Several promising
      strategies were suggested to address these challenges, including clearly defining
      residents' patient panels; adopting a team-based care approach; incorporating the
      model into academic curriculum and clinical training; proactive and ongoing
      education of health professionals, residents, and patients; involving residents
      in the change process and in adjustment strategies. CONCLUSIONS: To meet the
      challenges of implementing AA, decision-makers should consider exposing residents
      to AA during academic training and clinical internships, involving them in team
      work on arrival, engaging them as key actors in the implementation and in intra-
      and inter-professional collaborative models.

PMID- 29464985
TI  - Comparison of phase-contrast MR and flow simulations for the study of CSF
      dynamics in the cervical spine.
AB  - Background Investigators use phase-contrast magnetic resonance (PC-MR) and
      computational fluid dynamics (CFD) to assess cerebrospinal fluid dynamics. We
      compared qualitative and quantitative results from the two methods. Methods Four
      volunteers were imaged with a heavily T2-weighted volume gradient echo scan of
      the brain and cervical spine at 3T and with PC-MR. Velocities were calculated
      from PC-MR for each phase in the cardiac cycle. Mean pressure gradients in the PC
      MR acquisition through the cardiac cycle were calculated with the Navier-Stokes
      equations. Volumetric MR images of the brain and upper spine were segmented and
      converted to meshes. Models of the subarachnoid space were created from volume
      images with the Vascular Modeling Toolkit. CFD simulations were performed with a
      previously verified flow solver. The flow patterns, velocities and pressures were
      compared in PC-MR and CFD flow images. Results PC-MR images consistently revealed
      more inhomogeneous flow patterns than CFD, especially in the anterolateral
      subarachnoid space where spinal nerve roots are located. On average, peak
      systolic and diastolic velocities in PC-MR exceeded those in CFD by 31% and 41%,
      respectively. On average, systolic and diastolic pressure gradients calculated
      from PC-MR exceeded those of CFD by 11% and 39%, respectively. Conclusions PC-MR
      shows local flow disturbances that are not evident in typical CFD. The velocities
      and pressure gradients calculated from PC-MR are systematically larger than those
      calculated from CFD.

PMID- 29464986
TI  - Protective effects of thymoquinone on D-galactose and aluminum chloride induced
      neurotoxicity in rats: biochemical, histological and behavioral changes.
AB  - OBJECTIVES: Thymoquinone (TQ), the main active ingredient in Nigella sativa oil,
      exhibits various bioactivities. This study aimed to investigate the effect of TQ
      on neurobehavioral and neuropathological alterations induced by aluminum
      trichloride (AlCl3) and D-galactose (D-gal)-in male rats and to explore the
      related mechanisms. METHODS: D-gal (60 mg/kg day) and AlCl3 (10 mg/kg day) were
      given intraperitoneally (i.p.) once daily for 42 days and after 4 weeks TQ was
      concomitantly administered intragastrically (i.g.) (20 mg/kg/day) once daily for
      14 days. Then, memory function was evaluated by Morris water maze test (MWM).
      Superoxide dismutase (SOD), Total antioxidant capacity (TAC),
      Acetylcholinesterase (AChE) activities, and malondialdehyde (MDA), nitric oxide
      (NO), brain-derived neurotrophic factor (BDNF), and B-cell lymphoma-2 (Bcl-2)
      levels in whole brain were assessed with the biochemical technique. Tumor
      necrosis factor-alpha (TNF-alpha) and Acetylcholine (ACh) were also assessed
      using an immunohistochemical technique. RESULTS: Administration of TQ
      significantly improved cognition. In addition, TQ significantly increased SOD and
      TAC and decreased AChE activities. It also decreased MDA and NO levels as well as
      TNF-alpha immunoreactivity and increased BDNF and Bcl-2 levels as well as ACh
      immunoreactivity. DISCUSSION: Our results indicate that TQ prevents D-gal/AlCl3
      induced cognitive decline by enhancing cholinergic function and synaptic
      plasticity as well as attenuation of oxidative damage, neuronal apoptosis, and
      neuroinflammation. These results indicate that TQ holds potential for
      neuroprotection and may be a promising approach for the treatment of
      neurodegenerative disorders.

PMID- 29464989
TI  - Removal of residual functionalized ionic liquids from water by ultrasound
      assisted zero-valent iron/activated carbon.
AB  - Numerous applications of ionic liquids (ILs) are often accompanied by the
      generation of aqueous wastes. Due to the high toxicity and poor biodegradability
      of ILs, effective chemical treatment is of great importance for their removal
      from aqueous solution. In this work, an ultrasound-assisted zero-valent
      iron/activated carbon (US-ZVI/AC) micro-electrolysis technique was used to
      degrade residual functionalized ILs, 1-butyl-3-methyl benzimidazolium bromide
      ([BMBIM]Br) and 1-allyl-3-methylimidazolium chloride ([AMIM]Cl) in aqueous
      solution, and the degradation degree, degradation kinetics and possible
      degradation pathways were investigated. It was shown that the degradation of
      these functionalized ILs was highly efficient in the US-ZVI/AC system, and the
      degradation degree was as high as 96.1% and 92.9% in 110 min for [BMBIM]Br and
      [AMIM]Cl, respectively. The degradation of [BMBIM]Br could be described by the
      second-order kinetics model, and [BMBIM]+ was decomposed in two ways: (i)
      sequential cleavage of N-alkyl side chain of the cation produced three
      intermediates; (ii) the 2-positioned H atoms of the benzimidazolium ring were
      first oxidized, and then the imidazolium ring was opened. The degradation of
      [AMIM]Cl followed the first-order kinetics rule, and the 2,4,5-positioned H atoms
      of the imidazolium ring were oxidized to induce ring opening. In addition, the
      removal of total organic carbon was found to be >87%, which indicates that most
      of the ILs was mineralized in the degradation process. These results suggest that
      ultrasound-assisted ZVI/AC micro-electrolysis is highly effective for the removal
      of residual functionalized ILs from aqueous environment.

PMID- 29464988
TI  - Social support in the workplace for physicians in specialization training.
AB  - When becoming a specialist, learning-through-service plays a significant role.
      The workplace affords good opportunities for learning, but the service-learning
      period may also impose stress on phycisians in specialization training. In
      medical work, social support has proved to be a very important factor in managing
      stress. Social support may afford advantages also for learning and professional
      identity building. However, little was known about how social support is
      perceived by doctors in specialization training. This study aimed to understand
      the perceptions of physicians in specialization training regarding social support
      communication in their workplace during their learning-through-service period.
      The study was conducted qualitatively by inductively analyzing the physicians'
      descriptions of workplace communication. The dataset included 120 essays, 60 each
      from hospitals and primary healthcare centres. Physicians in specialization
      training explained the need of social support with the responsibilities and
      demands of their clinical work and the inability to control and manage their
      workloads. They perceived that social support works well for managing stress, but
      also for strengthening relational ties and one's professional identity. A
      leader's support was perceived as being effective, and both senior and junior
      colleagues were described as an important source of social support. Also co
      workers, such as the individual nurse partner with whom one works, was mentioned
      as an important source of social support. The results of this study indicate that
      social support works at the relational and identity levels, which is due to the
      multi-functional nature of workplace communication. For example, consultation
      functions as situational problem-solving, but also the tone of social interaction
      is meaningful. Thus, strengthening one's professional identity or collegial
      relationships requires further attention to workplace communication.
      Abbreviations PiST: Physician in specialization training.

PMID- 29464990
TI  - Exploring experiences among adopters during the diffusion of a novel dance
      intervention in Sweden.
AB  - There is a demand for interventions aimed at adolescent girls with psychosomatic
      problems. In 2013, positive results were reported from a dance intervention
      programme addressing girls with internalizing problems. The research team behind
      the intervention immediately received requests from municipalities and county
      councils interested in using the intervention. From an implementation point of
      view it is unclear what made the intervention spread without an active plan. The
      aim of this study was to explore adopters' experiences about the diffusion and
      initiation of a public health intervention targeting adolescent girls with
      internalizing problems. Interviews were conducted with 12 people who were engaged
      in initiating the intervention in different settings. Data were analysed using
      conventional content analysis, yielding three categories: perceived appeal and
      trustworthiness, convenient information, and contextual factors. The results
      reflected that the participants found that there was a need for an intervention
      and found the dance intervention to be evidence based and not too complex to
      perform. Further, there was available information on the project which could
      easily be distributed to decision makers and others. When initiating the
      intervention, factors related to economy, possibility for collaboration and
      recruitment were of importance.

PMID- 29464991
TI  - Labor-Management Cooperation in Illinois: How a Joint Union Company Team Is
      Improving Facility Safety.
AB  - This study of Afton Chemical Corporation's Sauget facility and its International
      Chemical Workers Union Council (ICWUC) Local 871C demonstrates how significant
      safety improvements can be made when committed leadership from both management
      and union work together, build trust, train the entire work force in U.S.
      Occupational Safety and Health Administration 10-hour classes, and communicate
      with their work force, both salaried and hourly. A key finding is that listening
      to the workers closest to production can lead to solutions, many of them more
      cost-efficient than top-down decision-making. Another is that making safety and
      health an authentic value is hard work, requiring time, money, and commitment.
      Third, union and management must both have leadership willing to take chances and
      learn to trust one another. Fourth, training must be for everyone and ongoing.
      Finally, health and safety improvements require dedicated funding. The result was
      resolution of more than one hundred safety concerns and an ongoing
      institutionalized process for continuing improvement.

PMID- 29464992
TI  - Childhood Obesity, Physical Activity, and Exercise-The Year That Was 2017: Normal
      Weight Obese-Are We Missing a Population in Need?

PMID- 29464993
TI  - Beyond Infanticide: How Psychological Accounts of Persons Can Justify Harming
      Infants.
AB  - It is commonly argued that a serious right to life is grounded only in actual,
      relatively advanced psychological capacities a being has acquired. The moral
      permissibility of abortion is frequently argued for on these grounds.
      Increasingly it is being argued that such accounts also entail the permissibility
      of infanticide, with several proponents of these theories accepting this
      consequence. We show, however, that these accounts imply the permissibility of
      even more unpalatable acts than infanticide performed on infants: organ
      harvesting, live experimentation, sexual interference, and discriminatory
      killing. The stronger intuitions against the permissibility of these 'pre
      personal acts' allow us to re-establish a comprehensive and persuasive reductio
      against psychological accounts of persons.

PMID- 29464994
TI  - Application of real-time nitrogen measurement for intermittent aeration
      implementation in a biological nitrogen removal system: performances and
      efficiencies.
AB  - Several automatic strategies for aeration control have been investigated so far
      to favor a significant decrement of energy consumptions in biological processes
      in wastewater treatment plants (WWTPs). Above all, the intermittent aeration
      process has demonstrated to have several advantages. This work reports the
      results of a case study made in a small municipal WWTP where an intermittent
      aeration control strategy based on the online measurement of real-time nitrogen
      forms has been implemented to optimize the nitrogen removal and the energy
      consumption in an activated process. High organic removal efficiency was achieved
      during the whole experimental period. Results indicated that nitrogen removal
      efficiency has been improved, especially during winter months, by the control
      strategy adopted that helped to determine the perfect length for the
      nitrification and denitrification phases. The intermittent aeration process
      increased the activity of the biomass, further selecting phosphate-accumulating
      bacteria and improving the growth of bacteria able to internally store carbon
      source. Excellent effects were achieved on energy and chemical consumption, with
      a reduction of about 15% and 23%, respectively. Finally, a 12% reduction of
      sludge production was also detected.

PMID- 29464995
TI  - Fabrication of calixarene-grafted magnetic nanocomposite for the effective
      removal of lead(II) from aqueous solution.
AB  - Magnetic nanocomposites adorned with calixarene were successfully prepared by
      immobilizing diethanolamine functionalized p-tert-butylcalix[4]arene (DEA-Calix)
      onto silica-coated magnetic nanoparticles (MNPs). The synthesis, surface
      morphology, purity, elemental composition and thermal stability of newly prepared
      nanocomposites were analyzed using FT-IR spectroscopy, scanning electron
      microscopy (SEM), energy dispersive spectroscopy (EDX), X-ray diffractometer
      (XRD), thermal gravimetric analysis (TGA) and vibrating sample magnetometer
      (VSM). Magnetic solid-phase adsorption (MSPA) was employed to explore the
      adsorption behavior of DEA-Calix-MNPs towards Pb(II) from water samples prior to
      its flame atomic absorption spectrometric analysis. The essential analytical
      factors governing the adsorption efficiency such as solution pH, mass of
      adsorbent, concentration and contact time have been investigated and optimized.
      The results depict that DEA-Calix-MNPs has excellent adsorption efficiency 97%
      (at pH 5.5) with high adsorption capacity of 51.81 mg g-1 for Pb(II) adsorption.
      Additionally, kinetic and equilibrium studies suggested that Pb(II) adsorption
      process follows a pseudo-second-order model and Langmuir isotherms, respectively.
      Real sample analysis also confirmed field applicability of the new DEA-Calix-MNPs
      adsorbent.

PMID- 29464996
TI  - Removal of diclofenac from a non-sterile aqueous system using Trametes versicolor
      with an emphasis on adsorption and biodegradation mechanisms.
AB  - This paper describes the search for procedures through which the xenobiotic
      pollutant diclofenac can be removed from non-sterile aquatic systems.
      Specifically, adsorption to solid supports (carriers) in combination with
      biodegradation by non-immobilized and immobilized white rot fungus Trametes
      versicolor were investigated. Batch experiments using polyurethane foam (PUF)
      carriers resulted in 99.9% diclofenac removal after 4 h, with monolayer
      adsorption of diclofenac to carrier and glass surfaces accounting for most of the
      diclofenac decrease. Enzymatic reactions contributed less, accounting for
      approximately < 0.5% of this decrease. In bioreactor experiments using PUF
      carriers, an initial 100% removal was achieved with biodegradation contributing
      approximately 7%. In batch experiments that utilized polyethylene-carriers with
      negligible immobilization of Trametes versicolor, a 98% total diclofenac removal
      was achieved after one week, with a biodegradation contribution of approximately
      14%. Five novel enzyme-catalyzed biodegradation products were tentatively
      identified in the batch-wise and bioreactor experiments using full scan ultra
      high-performance liquid chromatography-quadrupole/time of flight mass
      spectrometry. Both reduction and oxidation products were found, with the contents
      estimated to be at ug L-1 concentration levels.

PMID- 29464998
TI  - Response to letters regarding "Cosmetic talc as a risk factor for pleural
      mesothelioma: a weight of evidence evaluation of the epidemiology".

PMID- 29464997
TI  - The discovery of novel HDAC3 inhibitors via virtual screening and in vitro
      bioassay.
AB  - Histone deacetylase 3 (HDAC3) is a potential target for the treatment of human
      diseases such as cancers, diabetes, chronic inflammation and neurodegenerative
      diseases. Previously, we proposed a virtual screening (VS) pipeline named
      "Hypo1_FRED_SAHA-3" for the discovery of HDAC3 inhibitors (HDAC3Is) and had
      thoroughly validated it by theoretical calculations. In this study, we attempted
      to explore its practical utility in a large-scale VS campaign. To this end, we
      used the VS pipeline to hierarchically screen the Specs chemical library. In
      order to facilitate compound cherry-picking, we then developed a knowledge-based
      pose filter (PF) by using our in-house quantitative structure activity
      relationship- (QSAR-) modelling approach and coupled it with FRED and Autodock
      Vina. Afterward, we purchased and tested 11 diverse compounds for their HDAC3
      inhibitory activity in vitro. The bioassay has identified compound 2 (Specs ID:
      AN-979/41971160) as a HDAC3I (IC50 = 6.1 MUM), which proved the efficacy of our
      workflow. As a medicinal chemistry study, we performed a follow-up substructure
      search and identified two more hit compounds of the same chemical type, i.e. 2-1
      (AQ-390/42122119, IC50 = 1.3 MUM) and 2-2 (AN-329/43450111, IC50 = 12.5 MUM).
      Based on the chemical structures and activities, we have demonstrated the
      essential role of the capping group in maintaining the activity for this class of
      HDAC3Is. In addition, we tested the hit compounds for their in vitro activities
      on other HDACs, including HDAC1, HDAC2, HDAC8, HDAC4 and HDAC6. We have
      identified these compounds are HDAC1/2/3 selective inhibitors, of which compound
      2 show the best selectivity profile. Taken together, the present study is an
      experimental validation and an update to our earlier VS strategy. The identified
      hits could be used as starting structures for the development of highly potent
      and selective HDAC3Is.

PMID- 29464999
TI  - Molecular Characteristics of Hb New York [beta113(G15)Val->Glu, HBB: c.341T>A] in
      Thailand.
AB  - Hb New York or Hb Kaohsiung [beta113(G15)Val->Glu (GTG>GAG), HBB: c.341T>A] has
      been considered a rare beta hemoglobin (Hb) variant found originally in an
      Iranian woman and later in diverse populations but its genetic origin has not
      been elucidated. Here we report molecular and hematological descriptions of this
      variant found in the Thai population. Among 5643 subjects referred for
      hemoglobinopathy investigation during January 2015 to September 2017, 183 (3.2%)
      were found to carry several Hb variants, including beta chain variants (n = 135,
      2.4%), alpha chain variants (n = 33, 0.6%), Hb Lepore-Hollandia (NG_000007.3:
      g.63290_70702del) and Hb Lepore-Boston-Washington (NG_000007.3: g.63632_71046del)
      (deltabeta hybrid Hb) (n = 12, 0.2%) and delta chain variants (n = 3, 0.05%). Of
      patients with beta chain variants, six with normal high performance liquid
      chromatography (HPLC) patterns, had an abnormal Hb in zone 11 of capillary
      electrophoresis (CE), the amounts of which ranged from 29.6-45.4% with normal
      levels of Hb A2 and Hb F. DNA analysis identified a heterozygous Hb New York
      mutation in all cases. Further screening of alpha-thalassemia (alpha-thal)
      identified coinheritance of alpha+- and alpha0-thal in two of them who had
      reduced levels of Hb New York. Haplotype analysis suggested that the Thai Hb New
      York was likely associated with a single beta-globin haplotype [+ - - - - + +],
      indicating that it was of the same origin. Hematological findings and simple DNA
      assay based on allele-specific polymerase chain reaction (PCR) for rapid
      detection of Hb New York are presented.

PMID- 29465000
TI  - Long non-coding RNA FENDRR reduces prostate cancer malignancy by competitively
      binding miR-18a-5p with RUNX1.
AB  - CONTEXT: Prostate cancer (PCa) is one of the most commonly diagnosed malignancy
      in men in the western world. OBJECTIVE: We aim to investigate the biological role
      of long non-coding RNA FENDRR and its mechanism in PCa. MATERIALS AND METHODS: We
      determined the expression of FENDRR and miR-18a-5p in PCa tissues and examined
      the regulatory mechanism in PCa cell lines. RESULTS: FENDRR transcripts in human
      PCa tissues were significantly decreased compared with the normal controls.
      Reduced expression of FENDRR was correlated with the increase of pathological
      degree and poor prognosis in PCa patients. Upregulation of FENDRR inhibited cell
      proliferation, increased apoptosis and decreased invasion and migration ability,
      which was inhibited by miR-18a-5p mimic. Knockdown of FENDRR resulted in a
      significant increase of PCa cell proliferation and decrease of apoptosis and this
      effect was inhibited miR-18a-5p inhibitor. FENDRR and RUNX1 contain potential
      target sites for miR-18a-5p. miR-18a-5p mimic inhibited RUNX1 expression and
      luciferase activity. FENDRR could increase RUNX1 expression, which was inhibited
      by miR-18a-5p. The effect of FENDRR on cell proliferation, apoptosis and invasion
      and migration ability was suppressed by silence of RUNX1. DISCUSSION AND
      CONCLUSION: These results position FENDRR/miR-18a-5p/RUNX1 as a potential
      therapeutic target and biomarker for PCa.

PMID- 29465001
TI  - Revised and extended serum cotinine cut-offs to classify smokers and non-smokers.
AB  - PURPOSE: To revise and extend the previously published serum cotinine cut offs to
      classify smokers and non-smokers for US adolescents and adults. MATERIALS AND
      METHODS: Cross-sectional data (N = 10171) from National Health and Nutrition
      Examination Survey for 2011-2014 were used to compute serum cotinine cut-offs to
      classify smokers and non-smokers for US adults aged >=20 years and 2007-2014 (N =
      4583) data were used to compute serum cotinine cut-offs for US adolescents aged
      12-19 years. RESULTS: Specificities and sensitivities for the cut-offs among
      adults were >=95% and >=75% among adolescents. For adults, serum cotinine cut
      offs in ng/mL to classify smokers from non-smokers were 3.3 for the total
      population, 4.13 for males, 2.99 for females, 4.03 for non-Hispanic whites, 8.85
      for non-Hispanic blacks, 0.377 for Mexican Americans, 1.72 for other Hispanics
      and 1.41 for non-Hispanic Asians. For adolescents, serum cotinine cut-offs in
      ng/mL to classify smokers from non-smokers were 0.765 for the total population,
      1.1 for males, 0.408 for females, 1.2 for non-Hispanic whites, 1.98 for non
      Hispanic blacks, 0.215 for Mexican Americans and 0.321 for other Hispanics.
      CONCLUSIONS: Serum cotinine cut-offs to distinguish smokers from non-smokers for
      US adults and adolescents were developed.

PMID- 29465002
TI  - Prognostic and diagnostic value of elevated serum concentration of procalcitonin
      in patients with suspected heart failure. A review and meta-analysis.
AB  - PURPOSE: The diagnostic and prognostic significance of procalcitonin remains
      uncertain in HF patients. We reviewed and performed a meta-analysis of studies
      that measured PCT in HF patients, with or without infection. MATERIALS AND
      METHODS: We identified seven studies (9514 patients, 5810 with diagnoses of HF)
      eligible for our analysis, out of 247 examined. We estimated the serum PCT
      concentrations in patients with and without HF and/or infection and examined the
      mortality rates of patients with versus without elevated serum PCT
      concentrations. RESULTS: The mean age of the study samples ranged between 58 and
      81 years, the men proportion between 47% and 66%, the follow-up duration between
      22 and 180 days. The median PCT concentration in patients with HF and concomitant
      infections tended to be higher (0.26 ng/l [0.06, 0.46]) than in patients with HF
      alone (0.10 ng/l [0.08, 0.12]; p = 0.059). The mortality of patients suffering
      from HF and whose serum PCT concentrations were elevated was significantly higher
      than that of patients suffering from HF whose PCT concentrations were normal at
      30 (2.66 [1.74, 4.05]), 90 (2.12 [1.59, 2.83]) and 180 days (2.06 [1.13, 3.78]).
      CONCLUSIONS: In patients with HF, an elevated serum PCT concentration predicted
      the short-term risk of death.

PMID- 29465003
TI  - Editorial: In honor of Professor Peter Paul Speiser, Recipient of the Journal of
      Drug Targeting's Life-time Achievement Award for 2009.

PMID- 29465005
TI  - Influence of airborne particulates on respiratory tract deposition of inhaled
      toluene and naphthalene in the rat.
AB  - OBJECTIVE: Most studies report that inhaled volatile and semivolatile organic
      compounds (VOCs/SVOCs) tend to deposit in the upper respiratory tract, while
      ultrafine (or near ultrafine) particulate matter (PM) (~100 nm) reaches the lower
      airways. The objective of this study was to determine whether carbon particle co
      exposure carries VOCs/SVOCs deeper into the lungs where they are deposited.
      MATERIALS AND METHODS: Male Sprague-Dawley rats were exposed by inhalation (nose
      only) to radiolabeled toluene (20 ppm) or naphthalene (20 ppm) on a single
      occasion for 1 h, with or without concurrent carbon particle exposure (~5 mg/m3).
      The distribution of radiolabel deposited within the respiratory tract of each
      animal was determined after sacrifice. The extent of adsorption of toluene and
      naphthalene to airborne carbon particles under the exposure conditions of the
      study was also assessed. RESULTS: We found that in the absence of particles, the
      highest deposition of both naphthalene and toluene was observed in the upper
      respiratory tract. Co-exposure with carbon particles tended to increase
      naphthalene deposition slightly throughout the respiratory tract, whereas slight
      decreases in toluene deposition were observed. Few differences were statistically
      significant. Naphthalene showed greater adsorption to the particles compared to
      toluene, but overall the particle-adsorbed concentration of each of these
      compounds was a small fraction of the total inspired concentration. CONCLUSIONS:
      These studies imply that at the concentrations used for the exposures in this
      study, inhaled carbon particles do not substantially alter the deposition of
      naphthalene and toluene within the respiratory tract.

PMID- 29465004
TI  - Insulin resistance in an animal model of polycystic ovary disease is aggravated
      by vitamin D deficiency: Vascular consequences.
AB  - Hyperandrogenic state in females is accompanied with metabolic syndrome, insulin
      resistance and vascular pathologies. A total of 67%-85% of hyperandrogenic women
      suffer also from vitamin D deficiency. We aimed to check a potential interplay
      between hyperandrogenism and vitamin D deficiency in producing insulin resistance
      and effects on coronary resistance arteries. Adolescent female rats were divided
      into four groups, 11-12 animals in each. Transdermal testosterone-treated and
      vehicle-treated animals were kept either on vitamin D-deficient or on vitamin D
      supplemented diet for 8 weeks. Plasma sexual steroid, insulin, leptin and vitamin
      D plasma levels were measured, and oral glucose tolerance test was performed. In
      coronary arterioles, insulin receptor and vitamin D receptor expressions were
      tested by immunohistochemistry, and insulin-induced relaxation was measured in
      vitro on isolated coronary resistance artery segments. Testosterone impaired
      glucose tolerance, and it diminished insulin relaxation but did not affect the
      expression of insulin and vitamin D receptors in vascular tissue. Vitamin D
      deficiency elevated postprandial insulin levels and homeostatic model assessment
      insulin resistance. It also diminished insulin-induced coronary arteriole
      relaxation, while it raised the expression of vitamin D and insulin receptors in
      the endothelial and medial layers. Our conclusion is that both hyperandrogenism
      and vitamin D deficiency reduce sensitivity of coronary vascular tissue to
      insulin, but they do it with different mechanisms.

PMID- 29465006
TI  - Probiotic effects of anaerobic co-digestion substrates.
AB  - Manure is often added to stabilise anaerobic digesters especially when co
      digesting high-energy substrates such as whey. While different researchers have
      attributed its beneficial effect to various components including alkalinity,
      nutrients or trace elements this research instead aimed to determine whether
      microorganisms, such as lactic acid bacteria which are naturally present in the
      feedstocks, were having a notable beneficial effect on biogas production. Casein
      whey and cow manure were co-digested with primary sludge and produced 151.1%
      biogas compared to the control reactor digesting primary sludge alone. It was
      found that targeting the microorganisms in the manure via autoclaving decreased
      reactor performance to only 112.8% compared to the control potentially indicating
      that the manure is providing a probiotic effect. It was also found that storing
      casein whey (which is needed to balance out its seasonal production peaks)
      produces microorganisms that play a similarly important role as evidenced by the
      decrease in performance from 151.1% to 112.9% when they were removed via
      filtration.

PMID- 29465007
TI  - The Necrotrophic Fungus Macrophomina phaseolina Promotes Charcoal Rot
      Susceptibility in Grain Sorghum Through Induced Host Cell-Wall-Degrading Enzymes.
AB  - The cell-wall-degrading enzymes (CWDE) secreted by necrotrophs are important
      virulence factors. Although not unequivocally demonstrated, it has been suggested
      that necrotrophs induce hosts to cooperate in disease development through
      manipulation of host CWDE. The necrotrophic fungus Macrophomina phaseolina causes
      charcoal rot disease in Sorghum bicolor. An RNA-seq experiment was conducted to
      investigate the behavior of sorghum CWDE-encoding genes after M. phaseolina
      inoculation. Results revealed M. phaseolina's ability to significantly upregulate
      pectin methylesterase-, polygalacturonase-, cellulase-, endoglucanase-, and
      glycosyl hydrolase-encoding genes in a charcoal rot-susceptible sorghum genotype
      (Tx7000) but not in a resistant genotype (SC599). For functional validation,
      crude enzyme mixtures were extracted from M. phaseolina- and mock-inoculated
      charcoal-rot-resistant (SC599 and SC35) and -susceptible (Tx7000 and BTx3042)
      sorghum genotype stalks. A gel diffusion assay (pectin substrate) revealed
      significantly increased pectin methylesterase activity in M. phaseolina
      inoculated Tx7000 and BTx3042. Polygalacturonase activity was determined using a
      ruthenium red absorbance assay (535 nm). Significantly increased
      polygalacturonase activity was observed in two susceptible genotypes after M.
      phaseolina inoculation. The activity of cellulose-degrading enzymes was
      determined using a 2-cyanoacetamide fluorimetric assay (excitation and emission
      maxima at 331 and 383 nm, respectively). The assay revealed significantly
      increased cellulose-degrading enzyme activity in M. phaseolina-inoculated Tx7000
      and BTx3042. These findings revealed M. phaseolina's ability to promote charcoal
      rot susceptibility in grain sorghum through induced host CWDE.

PMID- 29465009
TI  - The Top 50 Most Cited Publications in Disability Sport: A Bibliometric Analysis.
AB  - Despite increasing publications in disability sport, no bibliometric analysis has
      been conducted to evaluate their impact.We conducted a systematic search of
      theWeb of Science Core Collection citation index on June 26, 2017 for
      publications published since 1980 to identify the top 50 most cited publications
      in disability sport. The top 50 cited publications were mainly articles and
      reviews published in the English language between 1993 and 2014. Most of the 148
      authors who contributed to these publications were based in Europe and North
      America. The majority of the publications can be categorized as sociological and
      psychological as well as training and competition effects. The most researched
      events were the Paralympics and Special Olympics. These top-cited publications
      have contributed to the development of disability sport research.

PMID- 29465008
TI  - Genetic variations in genes of the stress response pathway are associated with
      prolonged abstinence from heroin.
AB  - AIM: This study assesses whether genetic variants in stress-related genes are
      associated with prolonged abstinence from heroin in subjects that are not in long
      term methadone treatment. METHODS: Frequencies of 117 polymorphisms in 30 genes
      were compared between subjects with history of heroin addiction, either without
      agonist treatment (n = 129) or in methadone maintenance treatment (n = 923).
      RESULTS: SNP rs1500 downstream of CRHBP and an interaction of SNPs rs10482672
      (NR3C1) and rs4234955 (NPY1R/NPY5R) were significantly associated with prolonged
      abstinence without agonist treatment. CONCLUSION: This study suggests that
      variability in stress-related genes may contribute to the ability of certain
      subjects to remain in prolonged abstinence from heroin, possibly due to higher
      resilience to stress.

PMID- 29465012
TI  - Reducing sugar in our processed foods and beverages - will it make enough
      difference?

PMID- 29465013
TI  - The LiveWell Dorset behaviour change system.

PMID- 29465014
TI  - How successful will the sugar levy be in improving diet and reducing inequalities
      in health?

PMID- 29465015
TI  - WHO global priority pathogens list on antibiotic resistance: an urgent need for
      action to integrate One Health data.

PMID- 29465017
TI  - The prevention and management of cardiovascular diseases: focusing on health
      promotion and policy in South Korea.

PMID- 29465018
TI  - School lunches: getting healthy food on the menu in government-sponsored lunch
      programmes in the United States and Brazil.

PMID- 29465020
TI  - The success of pulmonary hypertension treatment: improved cardiac function by
      reducing the arterial load.

PMID- 29465022
TI  - Hand surgery in Australia: current status.

PMID- 29465021
TI  - The Federation of the European Societies for Surgery of the Hand: old new
      challenges.

PMID- 29465023
TI  - Remediation potential of immobilized bacterial consortium with biochar as carrier
      in pyrene-Cr(VI) co-contaminated soil.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and potentially toxic trace elements
      (PTEs) soil contamination have become areas of concern. Bioaugmentation is
      regarded as an effective bioremediation method, however it is difficult to
      simultaneously degrade organic compounds and remove PTEs with individual
      microbial strains. Therefore, the objective of this study was to evaluate the
      feasibility of using immobilized microbial consortia, including two PAH-degrading
      bacterial strains (W1 and W2) and a Cr(VI)-reducing bacterium (Y2), for the
      remediation of pyrene-Cr(VI) co-contaminated soil. Three immobilization methods
      were investigated: (1) bacterial consortium adsorption onto biochar (BC), (2)
      bacterial consortium entrapment in alginate beads (AC), (3) bacterial consortium
      adsorption on biochar and sequential entrapment in alginate beads (BAC). In
      addition, a free bacterial consortium (FC) was also used for comparison. Ten
      treatments were designed to illustrate the bioremediation efficiency of the free
      and immobilized consortia. The results show that treatments AC and BAC resulted
      in more efficient Cr(VI) removal compared with BC and FC. Pyrene levels in AC and
      BAC microcosms were reduced from 42.33 +/- 3.82 to 11.56 +/- 1.37 and 7.48 +/-
      0.39 mg kg-1, respectively. Bioavailable Cr (VI) in AC and BAC was significantly
      lower than that in other microcosms after 28 days' incubation. Both AC and BAC
      microcosms exhibited a higher level of dehydrogenase and fluorescein diacetate
      hydrolysis activity. Furthermore, soil microbial diversity was higher in AC and
      BAC microcosms compared with the others. Thus, the entrapped consortia may be
      useful for bioremediation of pyrene and Cr (VI) without compromising soil
      ecology.

PMID- 29465024
TI  - A prospective study of women with ASCUS or LSIL pap smears at baseline and HPV
      E6/E7 mRNA positive: a 3-year follow-up.
AB  - Human papillomavirus (HPV) testing is used in the triage of women with a
      borderline smear result. The efficiency of testing women with a low-grade
      squamous intraepithelial lesion (LSIL) and atypical squamous cells of
      undetermined significance (ASCUS) is less clear. For this reason we used a new
      HPV test that detects E6/E7 messenger RNA (mRNA), which might have a higher
      specificity. The objective of this prospective study was to assess whether HPV
      E6/E7 mRNA positivity in women with ASCUS and LSIL at baseline, is able to
      predict those women who have a high risk of developing a histological cervical
      intraepithelial neoplasia (CIN2) or worse lesion. We took into consideration the
      women's age and HPV DNA genotype and followed them up for 3 years. Cervical
      samples from women with high-risk HPV (HR-HPV) DNA-positive ASCUS (n = 90) or
      LSIL (n = 222) were tested for the presence of HR-HPV E6/E7 mRNA and the women
      were monitored for the development of histopathologically verified CIN2+.
      Thirteen patients with ASCUS and 17 with LSIL did not complete follow-up. All
      patients with LSIL and ASCUS, enrolled in this study, had confirmed lesions at
      the colposcopic examination. Follow-up was available for 312 women, 193 were
      positive in the HR-HPV DNA test and 93 had a HPV E6/E7 mRNA positive test.
      Finally, 22 women positive in the HPV DNA test for high-risk genotypes and with
      positive E6/E7 mRNA had a histologically confirmed CIN2+. Only two cases with
      negative HPV E6/E7 mRNA had CIN2+. The study shows that women positive in the HPV
      E6/E7 mRNA test have a greater risk of malignant progression of cervical lesions
      and therefore deserve greater attention and earlier check-ups.

PMID- 29465025
TI  - Swift and Low-Cost Surge in Chemical Threat Response: Is It Possible? The
      Experience of a French Hospital.
AB  - In 2016 France hosted the European football championship. In a context of an
      increased terrorist threat, Chemical, Bacteriological, Radiological, Nuclear
      (CBRN) attacks were considered possible. Three days prior to the beginning of the
      event, the Health Authorities required that a medium sized hospital close to a
      major potential target, prepare a chemical decontamination centre. Despite a low
      level of preparedness, little external help, and very few extra resources, an
      efficient decontamination chain (all premises necessary for the management of
      contaminated victims: from the entrance gate to the post-decontamination dressing
      cabins) was set up in 15 days (12 days after the unrealistic deadline). Numerous
      practical measures allowed three persons in CBRN personal protective equipment
      (PPE) to manage the whole chain, providing a maximum flow of 24 persons/hour.
      Volunteers were trained in PPE dressing, undressing and in decontamination
      procedures. This experience, offers a novel paradigm in managing chemical
      decontamination, in terms of attitude, and with adaptations to overcome practical
      constraints. It demonstrates that it is possible to set up a decontamination
      chain rapidly at very low cost. This provides an attractive option for less
      advanced countries and in humanitarian contexts. Some additional refinements,
      enhancements may be considered to further improve results. (Disaster Med Public
      Health Preparedness. 2018;12:649-656).

PMID- 29465026
TI  - Great boast, small roast on effects of selective serotonin reuptake inhibitors:
      response to a critique of our systematic review.
AB  - Our systematic review in BMC Psychiatry concluded that selective serotonin
      reuptake inhibitors (SSRIs) compared with placebo significantly increase the risk
      of serious adverse events (SAEs) in patients with major depression and the
      potential beneficial effects of SSRIs seem to be outweighed by the harms.
      Hieronymus et al. accused us of methodological inaccuracies and blatant errors.
      In their post-hoc analysis of our data, they reported that SSRIs only increase
      the risk of SAEs in elderly and seems safe for non-elderly patients. They also
      found our review misleading because our efficacy analyses were based on the 17
      item Hamilton Depression Rating Scale; we included suboptimal SSRI doses; and we
      missed some 'pivotal trials'. We do not agree with Hieronymus et al. regarding
      several of the 'errors' they claim that we have made. However, we acknowledge
      that they have identified minor errors and that we missed some trials. After
      rectifying the errors and inclusion of the missed trials by us and Hieronymus et
      al., we re-analysed the data. The updated analyses are even more robust and
      confirm our earlier conclusions. SSRIs significantly increase the risk of an SAE
      both in non-elderly (p=0.045) and elderly (p=0.01) patients [overall odds ratio
      1.39; 95% confidence interval (CI) 1.13 to 1.73; p=0.002; I2=0%]. Moreover, SSRIs
      did not change noticeably the 17-item Hamilton Depression Rating Scale, the
      internationally accepted scale (mean difference -2.02 points; 95% CI -2.38 to 
      1.66; p<0.00001). We found no differential effect of dose (p=0.20).

PMID- 29465028
TI  - ICTV Virus Taxonomy Profile: Rhabdoviridae.
AB  - The family Rhabdoviridae comprises viruses with negative-sense (-) single
      stranded RNA genomes of 10.8-16.1 kb. Virions are typically enveloped with bullet
      shaped or bacilliform morphology but can also be non-enveloped filaments.
      Rhabdoviruses infect plants and animals including mammals, birds, reptiles and
      fish, as well as arthropods which serve as single hosts or act as biological
      vectors for transmission to animals or plants. Rhabdoviruses include important
      pathogens of humans, livestock, fish and agricultural crops. This is a summary of
      the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy
      of Rhabdoviridae, which is available at www.ictv.global/report/rhabdoviridae.

PMID- 29465027
TI  - Correlation between measles vaccine doses: implications for the maintenance of
      elimination.
AB  - Measles eradication efforts have been successful at achieving elimination in many
      countries worldwide. Such countries actively work to maintain this elimination by
      continuing to improve coverage of two routine doses of measles vaccine following
      measles elimination. While improving measles vaccine coverage is always
      beneficial, we show, using a steady-state analysis of a dynamical model, that the
      correlation between populations receiving the first and second routine dose also
      has a significant impact on the population immunity achieved by a specified
      combination of first and second dose coverage. If the second dose is administered
      to people independently of whether they had the first dose, high second-dose
      coverage improves the proportion of the population receiving at least one dose,
      and will have a large effect on population immunity. If the second dose is
      administered only to people who have had the first dose, high second-dose
      coverage reduces the rate of primary vaccine failure, but does not reach people
      who missed the first dose; this will therefore have a relatively small effect on
      population immunity. When doses are administered dependently, and assuming the
      first dose has higher coverage, increasing the coverage of the first dose has a
      larger impact on population immunity than does increasing the coverage of the
      second. Correlation between vaccine doses has a significant impact on the level
      of population immunity maintained by current vaccination coverage, potentially
      outweighing the effects of age structure and, in some cases, recent improvements
      in vaccine coverage. It is therefore important to understand the correlation
      between vaccine doses as such correlation may have a large impact on the
      effectiveness of measles vaccination strategies.

PMID- 29465029
TI  - Essentiality of WalRK for growth in Bacillus subtilis and its role during heat
      stress.
AB  - WalRK is an essential two-component signal transduction system that plays a
      central role in coordinating cell wall synthesis and cell growth in Bacillus
      subtilis. However, the physiological role of WalRK and its essentiality for
      growth have not been elucidated. We investigated the behaviour of WalRK during
      heat stress and its essentiality for cell proliferation. We determined that the
      inactivation of the walHI genes which encode the negative modulator of WalK,
      resulted in growth defects and eventual cell lysis at high temperatures.
      Screening of suppressor mutations revealed that the inactivation of LytE, an dl
      endopeptidase, restored the growth of the DeltawalHI mutant at high temperatures.
      Suppressor mutations that reduced heat induction arising from the walRK regulon
      were also mapped to the walK ORF. Therefore, we hypothesized that overactivation
      of LytE affects the phenotype of the DeltawalHI mutant. This hypothesis was
      corroborated by the overexpression of the negative regulator of LytE, IseA and
      PdaC, which rescued the growth of the DeltawalHI mutant at high temperatures.
      Elucidating the cause of the temperature sensitivity of the DeltawalHI mutant
      could explain the essentiality of WalRK. We proved that the constitutive
      expression of lytE or cwlO using a synthetic promoter uncouples these expressions
      from WalRK, and renders WalRK nonessential in the pdaC and iseA mutant
      backgrounds. We propose that the essentiality of WalRK is derived from the
      coordination of cell wall metabolism with cell growth by regulating dl
      endopeptidase activity under various growth conditions.

PMID- 29465030
TI  - Novel host restriction factors implicated in HIV-1 replication.
AB  - Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host
      cellular proteins during its replication in the target cell. While many of these
      host cellular proteins facilitate viral replication, a number of them are
      reported to inhibit HIV-1 replication at various stages of its life cycle. These
      host cellular proteins, which are known as restriction factors, constitute an
      integral part of the host's first line of defence against the viral pathogen.
      Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an
      HIV-1 restriction factor, several human proteins have been identified that
      exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct
      mechanism of inhibition, the HIV-1 virus has equally evolved complex counter
      strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile
      alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5alpha are some
      of the best known HIV-1 restriction factors that have been studied in great
      detail. Recently, six novel restriction factors were discovered that exhibit
      significant antiviral activity: endoplasmic reticulum alpha1,2-mannosidase I
      (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine
      incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of
      this review is to discuss the antiviral mechanism of action of these six
      restriction factors and provide insights into the probable counter-evasion
      strategies employed by the HIV-1 virus. The recent discovery of new restriction
      factors substantiates the complex host-pathogen interactions occurring during HIV
      1 pathogenesis and makes it imperative that further investigations are conducted
      to elucidate the molecular basis of HIV-1 replication.

PMID- 29465031
TI  - [Management of cardiovascular complications secondary to medical treatment of
      cancer].
AB  - As the prognoses of both heart and cancer patients have improved along with a
      longer life expectancy in the general population, the prevalence of both heart-
      and cancer diseases is increasing. Thus, a larger proportion of cancer patients
      will have cardiovascular co-morbidity and an increased risk of cardiovascular
      complications during and after cancer treatment. In this article, the current
      knowledge on the prevention, monitoring and treatment of cardiotoxicity induced
      by medical anti-cancer treatment with focus on anthracyclines, trastuzumab and 5
      fluorouracil is described.

PMID- 29465032
TI  - [Coordinating rehabilitation and palliative care].
AB  - There is an increased focus on coordinating rehabilitation and palliative care
      (CRPC). A systematic Danish literature review on CRPC highlights the following:
      the main arguments and recommendations for such a coordination, that CRPC might
      be meaningful for patients throughout the disease trajectory and until the very
      end of it, that there is a lack of evidence-based research in this area, and that
      there is a lot of structural, organizational and professional challenges in
      securing CRPC.

PMID- 29465033
TI  - [Headache in children and adolescents].
AB  - Headache is an increasingly common symptom among children and adolescents with a
      prevalence of 58.4%, and it may have profound impact on everyday life. A poorer
      prognosis is seen for children, who are not referred to specialist care, and long
      term follow-up is shown to indicate a better outcome. A thorough headache history
      and a full neurological examination is vital to a correct diagnosis. The acute
      and prophylactic treatment is poorly studied, but acetaminophen and ibuprofen are
      first-line choices in acute treatment, and prophylactic treatment should be
      carried out by specialists.

PMID- 29465034
TI  - [Hypercalcaemia due to the milk-alkali syndrome].
AB  - This case report is about an 87-year-old woman with Alzheimer's disease and the
      milk-alkali syndrome, who took calcium carbonate as osteoporosis prophylaxis. We
      describe, how the milk-alkali syndrome can result in a triad of hypercalcaemia,
      metabolic alkalosis, and renal insufficiency. The syndrome is now the third most
      common cause of hypercalcaemia because of the use of calcium carbonate in
      osteoporosis prophylaxis and treatment, and the syndrome should be considered in
      patients with hypercalcaemia, as it may result in permanent renal impairment.

PMID- 29465035
TI  - [Insufficient CT scan in visualizing an intracerebral parenchymal damage in a six
      month-old boy].
AB  - A six-month-old boy fell over, and a crochet hook penetrated his skin underneath
      his left eye. The hook was removed, and an emergency physician found a Glasgow
      Coma Scale score of 6-7. A CT scan showed no cerebral or ophthalmic injury.
      However, the patient was persistently apathic with head- and gaze direction
      towards the left and a facial nerve palsy. An MRI showed a linear intracerebral
      lesion stretching through pons into the cerebellar vermis. The patient had
      neuropaediatric rehabilitation and recovered fully within months. The case is an
      example of CT scan being insufficient in visualizing intracerebral parenchymal
      damage.

PMID- 29465036
TI  - [Mycobacterium abscessus infection after cosmetic breast surgery in India].
AB  - A 36-year-old Danish woman underwent cosmetic breast surgery in India. Post
      operatively, she presented with infection and ulcers under the breasts, and
      dicloxacillin was administered. The patient did not return for follow-up. Two
      years later the ulcer under the right breast had not healed, and the patient
      returned to hospital, where a wound culture was done. The result showed
      Mycobacterium abscessus. Hence, cephalexin administration was instituted, but the
      ulcer did not heal, and it was excised. The subsequent healing was rapid.
      Mycobacterial infections in Denmark are rare, serious, and often resistant to
      antibiotics.

PMID- 29465037
TI  - Risk factors of peritonitis during early peritoneal dialysis in patients with
      ANCA-associated systemic vasculitis?.
AB  - This study investigated the risk factors of peritonitis during early peritoneal
      dialysis for renal failure in patients with antineutrophil cytoplasmic antibody
      (ANCA)-associated systemic vasculitis (AASV). This study enrolled hospitalized
      AASV patients with renal failure who underwent peritoneal dialysis at the
      Department of Nephrology of our hospital between 2008 and 2015. The primary aim
      of this study was to perform a retrospective analysis to characterize peritonitis
      during the early period (<= 8 weeks) of dialysis, and to compare the differences
      in initial clinical manifestations, vasculitis activity, immunosuppressive
      therapies prior to the renal replacement therapy, and prognosis between patients
      with or without peritonitis. The secondary aim of this study was to conduct a
      literature review of peritoneal dialysis in patients with vasculitis. All 14
      enrolled AASV patients had myeloperoxidase (MPO)-positive microscopic
      polyangiitis (MPA). Six patients (of whom 2 died) withdrew from peritoneal
      dialysis due to peritonitis caused by enteric bacteria during the early period of
      dialysis. Their mean Birmingham vasculitis activity score (BVAS) during the early
      AASV onset was 31.67 +/- 3.98, with significant symptoms of gastrointestinal
      involvement. Also, their BVAS score, anti-MPO antibody titer, erythrocyte
      sedimentation rate, C-reactive protein level, serum ANCA level, and
      glucocorticoid dose were higher than the AASV patients without peritonitis (all p
      < 0.05). AASV patients with a higher level of vasculitis (BVAS score > 30) during
      onset as well as gastrointestinal symptoms had a higher risk for intestinal
      peritonitis. Therefore, peritoneal dialysis is not recommended as a first-choice
      renal replacement therapy for such patients.?.

PMID- 29465038
TI  - Modelling of nanoscale multi-gate transistors affected by atomistic interface
      roughness.
AB  - Interface roughness scattering (IRS) is one of the major scattering mechanisms
      limiting the performance of non-planar multi-gate transistors, like Fin field
      effect transistors (FETs). Here, two physical models (Ando's and multi-sub-band)
      of electron scattering with the interface roughness induced potential are
      investigated using an in-house built 3D finite element ensemble Monte Carlo
      simulation toolbox including parameter-free 2D Schrodinger equation quantum
      correction that handles all relevant scattering mechanisms within highly non
      equilibrium carrier transport. Moreover, we predict the effect of IRS on
      performance of FinFETs with realistic channel cross-section shapes with respect
      to the IRS correlation length (Lambda) and RMS height ([Formula: see text]). The
      simulations of the n-type SOI FinFETs with the multi-sub-band IRS model shows its
      very strong effect on electron transport in the device channel compared to the
      Ando's model. We have also found that the FinFETs are strongly affected by the
      IRS in the ON-region. The limiting effect of the IRS significantly increases as
      the Fin width is reduced. The FinFETs with [Formula: see text] channel
      orientation are affected more by the IRS than those with the [Formula: see text]
      crystal orientation. Finally, Lambda and [Formula: see text] are shown to affect
      the device performance similarly. A change in values by 30% (Lambda) or [Formula:
      see text] ([Formula: see text]) results in an increase (decrease) of up to
      [Formula: see text] in the drive current.

PMID- 29465039
TI  - Charge screening-controlled Verwey phase transition in Fe3O4/SrTiO3
      heterostructure.
AB  - Despite intensive investigations into the Verwey phase transition of Fe3O4 over
      half a century, the mechanism of this phase transition remains controversial and
      needs further research. In this work, we build the Fe3O4/SrTiO3 multiferroic
      heterostructure and investigate the temperature dependence of its saturation
      magnetization under various electric fields. It is found that the charge
      screening effect not only influences the magnetization but also induces the
      temperature of the Verwey phase transition shifting ~13 K. It suggests that the
      Verwey phase transition has certain correlations with the electron distribution
      and the change of the number of minority spin electrons in the trimerons plays a
      dominant role in the temperature shift of the phase transition.

PMID- 29465040
TI  - Giant magnetic anisotropy and robust quantum anomalous Hall effect in boron-doped
      graphene with Re-adsorption.
AB  - Recently topological materials have attracted much attention due to their
      quantization transports as well as edge states. It will be excellent to realize
      the robust quantum anomalous Hall transports in graphene-based devices. Using
      density-functional theory and tight-binding method, we investigated the
      structural, magnetic and topological properties for the boron-doped graphene with
      Re-adsorption. A large band-gap of 32.5 meV is opened by the Rashba spin-orbital
      coupling, and the band-gap is robust against the shape deformation of  +/
      [Formula: see text] along the zigzag direction. Giant magnetic anisotropy emerges
      in this adsorption system together with the Fermi level lying in the band gap.
      Both the magnetic anisotropy and the band gap can be tuned by a moderate electric
      field. Calculations reveal that the system exhibits the quantization transports
      with the Chern number [Formula: see text].

PMID- 29465041
TI  - Dynamical, structural and chemical heterogeneities in a binary metallic glass
      forming liquid.
AB  - As it approaches the glass transition, particle motion in liquids becomes highly
      heterogeneous and regions with virtually no mobility coexist with liquid-like
      domains. This complex dynamic is believed to be responsible for different
      phenomena including non-exponential relaxation and the breakdown of the Stokes
      Einstein relation. Understanding the relationships between dynamical
      heterogeneities and local structure in metallic liquids and glasses is a major
      scientific challenge. Here we use classical molecular dynamics simulations to
      study the atomic dynamics and microscopic structure of [Formula: see text] alloy
      in the supercooling regime. Dynamical heterogeneities are identified via an
      isoconfigurational analysis. We demonstrate the transition from isolated to
      clustering low mobility with decreasing temperature. These slow clusters, whose
      sizes grow upon cooling, are also associated with concentration fluctuations,
      characterized by a Zr-enriched phase, with a composition [Formula: see text]. In
      addition, a structural analysis of slow clusters based on Voronoi tessellation
      evidences an increase with respect of the bulk system of the fraction of Cu atoms
      having a local icosahedral order. These results are in agreement with the
      consolidated scenario of the relevant role played by icosahedral order in the
      dynamic slowing-down in supercooled metal alloys.

PMID- 29465042
TI  - Room-temperature superparamagnetism due to giant magnetic anisotropy in Mo S
      defected single-layer MoS2.
AB  - Room-temperature superparamagnetism due to a large magnetic anisotropy energy
      (MAE) of a single atom magnet has always been a prerequisite for nanoscale
      magnetic devices. Realization of two dimensional (2D) materials such as single
      layer (SL) MoS2, has provided new platforms for exploring magnetic effects, which
      is important for both fundamental research and for industrial applications. Here,
      we use density functional theory (DFT) to show that the antisite defect (Mo S )
      in SL MoS2 is magnetic in nature with a magnetic moment MU of  ~2 [Formula: see
      text] and, remarkably, exhibits an exceptionally large atomic scale MAE [Formula:
      see text] of  ~500 meV. Our calculations reveal that this giant anisotropy is the
      joint effect of strong crystal field and significant spin-orbit coupling (SOC).
      In addition, the magnetic moment MU can be tuned between 1 [Formula: see text]
      and 3 [Formula: see text] by varying the Fermi energy [Formula: see text], which
      can be achieved either by changing the gate voltage or by chemical doping. We
      also show that MAE can be raised to  ~1 eV with n-type doping of the MoS2:Mo S
      sample. Our systematic investigations deepen our understanding of spin-related
      phenomena in SL MoS2 and could provide a route to nanoscale spintronic devices.

PMID- 29465043
TI  - The Intraoral Ultrasonography in Dentistry.
AB  - Ultrasonography (USG) is a diagnostic method that the ultrasonic image is created
      by ultrahigh-frequency sound waves, which have an acoustic frequency above the
      threshold of human hearing. Compared to other medical imaging methods, USG has
      several advantages of being real time, portable, inexpensive, radiation free, and
      noninvasive. In the medicine, most of the USG applications are transcutaneous.
      However, intraoral USG has been a relatively rare application, it has recently
      been drawing more interest. Intraoral USG is also used in dentistry for examining
      the salivary glands and ducts, as well as the mouth floor, the buccal, labial,
      and palatal mucosa, the tongue, periodontal tissues, and periapical lesions. The
      main purpose of this review is to provide detailed information about intraoral
      USG applications in dentistry.

PMID- 29465044
TI  - Antimicrobial Effect of Toothpastes Containing Fluoride, Xylitol, or Xylitol
      Probiotic on Salivary Streptococcus mutans and Lactobacillus in Children.
AB  - Aim: This in vivo study was designed to compare the antimicrobial effect of
      toothpastes containing fluoride, xylitol, or xylitol-probiotic on Streptococcus
      mutans and Lactobacillus in 13-15-year-old children. Materials and Methods: The
      study consisted of 60 pediatric patients who were randomly divided into three
      groups of 20 each. Group 1 recieved fluoride toothpaste (Colgate Max Fresh),
      group 2 used xylitol toothpaste (Xyliwhite), and group 3 used xylitol-probiotic
      toothpaste (PerioBiotic). Participants were asked to use the allocated dentifrice
      two times a day for 6 weeks. We performed tests on the saliva samples at the
      beginning of the study and after 6 weeks' duration following the use of
      toothpaste. The Statistical Package for the Social Sciences version 15 software
      and chi-square test were used for data analysis. Results: PerioBiotic toothpaste
      and Colgate Max Fresh toothpaste showed significant reduction in the number of
      participants who, prior to commencing the study, were diagnosed with a high
      number of cariogenic bacteria. On the contrary, no significant changes were
      observed with respect to the number of participants with a very high number of S.
      mutans and Lactobacillus on Xyliwhite toothpaste group. Conclusion: In the light
      of the data obtained in this in-vivo study, a new innovational aspect has been
      reached in the use of probiotics to ensure the balance between bacterial flora in
      the oral cavity. In daily routine, the administration of probiotics to children
      is difficult. The toothpaste can be used as a vehicle to transport probiotics to
      children's mouth.

PMID- 29465045
TI  - Sugammadex Improves Neuromuscular Function in Patients Receiving Perioperative
      Steroids.
AB  - Context: Sugammadex has steroid-encapsulating effect. Aim: This study was
      undertaken to assess whether the clinical efficacy of sugammadex was altered by
      the administration of steroids. Setting and Design: Sixty patients between 18 and
      60 years of age with the American Society of Anesthesiologists I-IV and
      undergoing elective direct laryngoscopy/biopsy were included in this study.
      Materials and Methods: Patients were assigned to two groups based on the
      intraoperative steroid use: those who received steroid (Group S) and who did not
      (Group C). After standard general anesthesia, patients were monitored with the
      train of four (TOF) monitoring. The preferred steroid and its dose, timing of
      steroid administration, and TOF value before and after sugammadex as well as the
      time to recovery (TOF of 0.9) were recorded. Statistical Analysis Used: SPSS
      software version 17.0 was used for statistical analysis. Results: There is no
      statistically significant difference between groups in terms of age, gender,
      preoperative medication use, and TOF ratio just before administering sugammadex.
      The reached time to TOF 0.9 after sugammadex administration was significantly
      shorter in Group S than Group C (P < 0.05). A within-group comparison in Group S
      showed no difference in TOF ratio immediately before sugammadex as well as the
      dose of sugammadex in those who received prednisolone; time to TOF 0.9 was higher
      in prednisolone receivers as compared to dexamethasone receivers (P < 0.05). 
      Conclusion: In patients receiving steroids, and particularly dexamethasone, an
      earlier reversal of neuromuscular block by sugammadex was found, in contrast with
      what one expect. Further studies are required to determine the cause of this
      effect which is probably due to a potential interaction between sugammadex and
      steroids.

PMID- 29465046
TI  - Clinical and Laboratory Features of Metformin Intoxication in Suicidal Patients
      Attending an Intensive Care Unit.
AB  - Introduction: This study has been performed for the purpose of researching the
      complications occurred at patients who took metformin overdose in an attempt to
      suicide. None of the patients has the diagnosis of diabetes mellitus and never
      used metformin. Materials and Methods: This retrospective cross-sectional study
      was carried out with 21 patients who has neither diagnosed diabetes mellitus nor
      taken metformin for suicide before. Results: It was observed that there is a
      moderate, negative (r = -0.63) statistically significant correlation (P < 0.001)
      between the time of applying to the hospital and arterial blood pH at the arrival
      and a statistically significant positive mild correlation (P < 0.041) between
      applying and blood lactate level (r = 0.45), and a moderate positive (r = 0.63)
      and statistically significant correlation (P < 0.001) between the total metformin
      dose and blood lactate level at the arrival and a positive, moderate (r = 0.68)
      significant correlation (P < 0.001) between the creatinine and metformin dose at
      the arrival. Lactic acidosis has been detected at 8 of 21 patients, 6 patients
      were hemodialized, 2 patients needed mechanical ventilation, and 2 patients died.
      It is observed that there is no mortality for early hemodialized patients.
      Conclusion: The most important reason of the mortality in patients who has
      metformin intoxication is metformin-associated lactic acidosis (MALA). It was
      considered that hemodialysis therapy could be effective in MALA.

PMID- 29465047
TI  - Knowledge and Practice of Standard Precautions by Health-Care Workers in a
      Tertiary Health Institution in Enugu, Nigeria.
AB  - Background: Standard precautions (SPs) are crucial in protecting both health-care
      workers (HCWs) and patients from nosocomial infections. This study assessed the
      knowledge and practices of SP among HCWs in tertiary health-care facilities.
      Methods: : This descriptive study was done in October 2014 among 629 HCWs at the
      University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu State. A pretested
      questionnaire was used and analysis done using SPSS version 13. Results: The HCWs
      studied were 629, mostly females (64.4%), married (62.3%), Christians (94%), and
      within 20-59 years. Majority were nurses (46.1%) working in the wards. Over 90%
      of respondents had heard of SP, mainly from formal training (62%). Over 70% could
      define SP, 74.6% had knowledge of when SP is needed and> 70% identified most
      components of SP. Over 90% agreed that SPs are useful and that employers should
      provide SP training. Most respondents washed hands after removal of gloves
      (73.6%) and before leaving patient's care area (33.1%). More than 70% had been
      exposed to patient's body fluids and washed the exposed part with water, soap,
      and disinfectant (52.1%). Gloves were the most commonly used personal protective
      equipment (PPE) (53.4%) and the major reason for inconsistent use was irregular
      access (57.7%). Over 50% recap needles before discarding. Exposure to patients'
      serum was significantly higher among doctors and nurses P < 0.05, while the use
      of PPEs was highest among the laboratory scientists (82.4%). Those who were
      trained on SP (70.8%) and PPE (69.7) were significantly more likely to use PPEs,
      P < 0.05. Conclusions: SP training and regular provision of PPEs are vital in
      compliance to SP.

PMID- 29465048
TI  - Evaluation of Teeth Development in Unilateral Cleft Lip and Palate Patients in
      Mixed Dentition by Using Medical Image Control Systems.
AB  - Objectives: The aim of this study was to evaluate the crown and root development
      in patients with cleft lip and palate using medical software programmes.
      Materials and Methods: In our study, 25 patients with mixed dentition unilateral
      cleft lip and palate were examined with cone-beam computed tomography (CBCT). The
      tomography images obtained as high resolution medical images on the computer
      control system (MIMICS 15.0, Materialise, Leuven, Belgium and SOLIDWORKS 2014
      Premium, Concord, Massachusetts) were converted to three-dimensional volumetric
      images. These three-dimensional images of the cleft on the sides of the teeth in
      the crown and root growth were measured by mesiodistal length and crown/root rate
      with volume and area. These measurements were compared with a control group of
      healthy individuals. Results: There were no statistically significant differences
      in the volume, surface area and MD size, crown/root ratio of central incisor,
      canine, first premolar and second premolar teeth within defect, and healthy
      teeth. However, it was found that there was a significant difference between the
      volume, surface area and MD size, and crown/root ratio of the lateral teeth in
      each group. Conclusion: In particular, among patients with cleft lip and palate,
      on obtaining a solid model of the tooth structure by using these programs, tooth
      development can be examined in more detail, diagnosis can be made more reliable,
      as well as in treatment planning. We believe that these programs can be used to
      resolve certain limitations such as a lack of an application to be used in
      routine dental treatment and in particular the need to do more study.

PMID- 29465049
TI  - The Effect on Survival and Mortality of the Highest SUVmax Value on Metastatic
      Foci in Postoperative Kidney Tumors.
AB  - Objective: One-third of patients newly diagnosed with a kidney tumor have
      metachoronous disease, 25-50% have synchronous metastasis, and approximately 30
      40% of patients have metastasis at the time of diagnosis. Metastasis mostly
      occurs in the lungs, regional lymph nodes, bones, and liver. The present study
      was aimed to determine the effect on mortality the values of standard uptake
      value (SUV)max measured with positron emission tomography (PET) in metastases of
      kidney tumors. Material and Methods: A retrospective review was conducted of the
      files of 77 patients newly diagnosed with kidney tumor and disease staging
      determined with PET in the Nuclear medicine Department of Saglik Bilimleri
      University Diyarbakir Gazi Yasargil Training and Research Hospital between August
      2007 and April 2012. The gender, age, histological types, metastases, SUVmax
      values, and dates of death of the patients were recorded in the SPSS software.
      Results: It was observed that higher SUVmax values indicated a shorter survival
      time (r = .303) (P = 0.022). Patients with metastasis lived for a shorter period
      (P < 0.001), particularly those with liver metastasis (r = .515) (P = 0.049).
      Metastases were most frequently seen in lymph nodes (42.1%); the SUVmax values of
      lung metastases were higher (P = 0.025) and papillary carcinomas showed higher
      SUVmax uptake (P = 0.015). Conclusions: In the present study, it was concluded
      that the higher the SUVmax value the shorter the survival time. The survival time
      of patients with metastasis was shorter, and this could be estimated through the
      measured SUVmax values.

PMID- 29465050
TI  - Antibacterial Effect of Surface Pretreatment Techniques against Streptococcus
      Mutans.
AB  - Objective: The aim of this study was to evaluate the antibacterial surface
      pretreatment methods against Streptococcus mutans within the infected dentin
      surface using a tooth cavity model. Material and Methods: Seventy-two cavities
      were prepared on caries-free third molars (n = 8). After sterilization, teeth
      were inoculated with S. mutans for 48 h. One cavity of each tooth was used to
      evaluate the infection. Following inoculation, infected cavity surfaces were
      treated either with (1) Er:YAG Laser (1W; 5x5s, Smart 2940D Plus, Deka Laser),
      (2) Ozone (80s; HealOzone, Kavo), (3) ErYAG-Ozone combination, (4) Er:YAG-Ozone
      CHX combination, (5) Chlorhexidine (CHX), (6) Clearfil Protect Bond (PB), (7)
      potassium-titanyl-phosphate (KTP) Laser (1W; 60 s, SMARTLITE D, Deka Laser), (8)
      KTP-Ozone combination, and (9) KTP-Ozone-CHX. Standardized amounts of dentin
      chips were obtained from the cavity walls, and the number of bacteria recovered
      was counted. Kruskal-Wallis test was used for statistical analyzes. Results: Both
      sole antibacterial materials, CHX or Protect Bond application, exhibited the most
      effective antibacterial activity with 125 and 156 CFU is an acronym of "colony
      forming unit" usullay mentioned by acronym. (CFU/ml), respectively, among the
      groups evaluated (P < 0.05). Er:YAG laser irradiation and its combinations with
      other antibacterial surface pretreatment applications also inhibited the
      bacterial growth with, respectively, 1444, 406, and 294 CFU/ml bacterial recovery
      being more efficient than KTP laser irradiation and ozone combinations.
      Conclusions: As an alternative device with photodynamic effects, Er:YAG and KTP
      laser irradiations and their further combinations during the cavity pretreatment
      procedure with chlorhexidine and ozone treatments exerted antibacterial effect
      against S. mutans, whereas chlorhexidine and antibacterial dentin bonding
      application solely have the highest antibacterial effects.

PMID- 29465051
TI  - Resistance Pattern and Detection of Metallo-beta-lactamase Genes in Clinical
      Isolates of Pseudomonas aeruginosa in a Central Nigeria Tertiary Hospital.
AB  - Background: : Acquired metallo-beta-lactamases (MBLs) pose serious problem both
      in terms of treatment and infection control in the hospitals and report across
      the world showed an increase in their prevalence. However, there is a paucity of
      data from Africa, and their report is rare in Nigeria. Aim: : This study aimed to
      determine the prevalence of acquired MBL-resistant genes in carbapenem-resistant
      Pseudomonas aeruginosa in Abuja, North Central Nigeria. Materials and Methods: :
      Two hundred nonduplicate, consecutive isolates of P. aeruginosa from clinical
      samples submitted to the Medical Microbiology Laboratory of National Hospital,
      Abuja were screened for carbapenem resistance using imipenem and meropenem.
      Phenotypic detection of MBL-producing strains was determined using Total MBL
      confirm kits and E-test strips on isolates that were resistant to both Imipenem
      and meropenem. The MBL genes were detected using multiplex polymerase chain
      reaction, while the gene variant was determined by sequencing. Results: : Twenty
      two MBL-producing strains were detected phenotypically, but only 5 harbored the
      blaVIM-1 gene, giving a prevalence of 2.5%. These 5 strains were resistant to all
      the antipseudomonal antibiotics tested except Aztreonam and Colistin. Other
      common MBL-genes were not detected. Conclusion: : The prevalence of MBL-producing
      strains of P. aeruginosa which poses serious challenge for therapeutics and
      infection control is currently low in Abuja, North Central, Nigeria. Therefore,
      rational use of the carbapenems and other antipseudomonal antibiotics, regular
      surveillance and adequate infection control measures should be instituted to
      limit further spread.

PMID- 29465052
TI  - Nasotracheal Intubation in Children for Outpatient Dental Surgery: Is Fiberoptic
      Bronchoscopy Useful?
AB  - Background: The aim of our study was to compare the hemodynamic responses and
      adverse events associated with nasotracheal intubation (NTI) using a fiberoptic
      bronchoscope (FOB) and a direct laryngoscope (DLS) in children undergoing general
      anesthesia for outpatient dental surgery. Methods: Eighty children (aged 5-15
      years) were scheduled to undergo outpatient dental surgery under general
      anesthesia and of these children those who required NTI were included. Results:
      NTI was significantly longer in the FOB group (P = 0.03). In both groups,
      systolic blood pressure (SBP) and heart rate (HR) significantly decreased after
      the induction of anesthesia when compared with the baseline values. SBP was
      significantly higher in both groups at intubation and 1 and 3 min after
      intubation when compared with postinduction. SBP significantly increased in the
      DLS group compared with the FOB group at intubation and 1 min after intubation.
      HR was significantly increased at intubation and 1 min after intubation in the
      DLS group compared with the FOB group. Nose bleeding after intubation was
      significantly more frequent in the DLS group (30%) than in the FOB group (7.5%)
      (P = 0.034). The incidence of sore throat 24 h after surgery was 20% (8/40) in
      the DLS group and 2.5% (1/40) in the FOB group (P = 0.014). Conclusions: There
      are fewer hemodynamic responses and adverse events in the FOB group than in the
      DLS group; therefore, FOB can be safely used for NTI in children undergoing
      outpatient dental surgery, and FOB may be more successful than DLS for NTI.

PMID- 29465053
TI  - Erythropoietic Response to Anaemia of Dialysis Naive Patients with Chronic Kidney
      Disease in Zaria, North-West Nigeria.
AB  - Introduction: Chronic kidney disease (CKD) is a global health problem with an
      increasing prevalence worldwide. Anemia is one of its consistent and severe
      hematological complications although its mechanism is not fully elucidated. The
      primary defect could manifest as serum erythropoietin (sEPO) deficiency or EPO
      resistance. We set out to determine the erythropoietic response to anemia of
      patients with CKD and its relationship with their iron status in a cross
      sectional descriptive study of 91 patients in various stages of CKD. Materials
      and Methods: Soluble transferrin receptor (sTfR), sEpo, and serum ferritin levels
      were determined using ELISA method (Diagnostic Automation Inc and WKEA med
      supplies corp.). Data generated were analyzed using Epi Info version 3.5.3 and
      level of statistical significance was set at <=0.05. Results: Participants
      comprised of 50 females (54.9%) and 41 (45.1%) males with an overall mean age of
      47 +/- 15 years. The major causes of CKD were hypertension (HTN) (50.54%),
      diabetes mellitus (DM) (6.59%), and HTN + DM (19.78%). The mean hemoglobin (Hb)
      concentration of the participants was 10.97 +/- 2.28 g/dl; the red cell indices
      were within normal ranges except for Red cell distribution width-Coefficient of
      variation (%) which was elevated (16.29%). The mean serum ferritin, sTfR, and
      sEpo were 70.58 +/- 46.44 ng/ml (interquartile range [IQR] 82.00), 22.9 +/- 49.7
      ng/ml (IQR 15.00), and 12.49 +/- 33.47 IU/L (IQR 6.00), respectively, with a high
      variance. Serum ferritin and sTfR are consistently low across the stages of CKD
      (range between 54.54 ng/ml and 88.64 ng/ml), but sEPO for stage 3 and 4 showed a
      2-fold increase when compared to normal level at Hb 10.97 g/dl (29.54 IU/L and
      38.83 IU/L, respectively). Correlation between sTfR and sEpo (r2 = 0.96, P =
      0.001), while between sEpo and serum ferritin (r2 = 0.02, P = 0.185), and between
      Hb and stage of CKD undulating (r2 = 0.41, P = 0.001). Conclusion: In contrast to
      some existing literature, this study has demonstrated that EPO resistance and
      iron deficiency contributes to anemia in CKD and serum ferritin can be used to
      assess the iron level of dialysis naive CKD patients at every stage of the
      disease.

PMID- 29465054
TI  - Evaluation of the School Environment of Public and Private Schools in Enugu to
      Ensure Child Health Promotion.
AB  - Objectives: Poor maintenance of school environment can cause or worsen illnesses
      among schoolchildren. The objective of this study was to assess the healthfulness
      of school environments of primary schools in Enugu East, Nigeria, and to compare
      the difference if any between public and private schools. Study Design: This was
      a cross-sectional noninterventional study of the school environments in Enugu
      East, Nigeria. Methods: Multistage sampling method was used to select the sample
      population. The participating schools were inspected and their head teachers were
      interviewed using a questionnaire. Scores were awarded using the School Health
      Program Evaluation scale. Results: Thirty-three schools were studied. The most
      common source of water for most schools was well. Eleven schools dump refuse
      openly. Three public schools only had functional toilets. All public schools were
      adequately ventilated and lit. One private school had a foodservice area. Ten
      schools did not have a play field, while three public schools had soaps for
      handwashing. The mean scores for public and private schools were 33.00 and 37.86,
      respectively. Three schools only attained the minimum score of 57 of a maximum of
      66. Conclusion: The environment of primary schools in Enugu east, Nigeria, is
      unhealthy and unfriendly and currently cannot promote and protect the health of
      the schoolchildren.

PMID- 29465055
TI  - Evaluation of the Effect of Platelet-Rich Fibrin on the Alveolar Osteitis
      Incidence and Periodontal Probing Depth after Extracting Partially Erupted
      Mandibular Third Molars Extraction.
AB  - Aims: To evaluate whether the alveolar osteitis (AO) incidence after extracting
      partially erupted third molars differs when platelet-rich fibrin (PRF) is
      administered in the alveolar socket and to assess the influence of PRF on
      postoperative pain levels and periodontal probing depth. Settings and Design: In
      this split-mouth randomized study, 50 patients (17 men/ 33 women; mean age, 23.96
      years) with bilateral symmetric partially erupted mandibular third molars were
      enrolled. Material and Methods: PRF was randomly placed in one extraction socket,
      whereas the other socket was left empty. A verbal rating scale was used to
      evaluate postoperative pain levels. AO development was evaluated on the 7th
      postoperative day. At 3 months postoperatively, periodontal probing depth was
      measured on the distal surface of the second molars. Results: In total, 8% of
      patients in the PRF group and 18% of the patients in the control group were
      diagnosed with AO. None of the smokers in the PRF group and 37.5% smokers in the
      control group were diagnosed with AO. Mean postoperative pain levels were lower
      in the PRF group than in the control group at all time points. At 3 months
      postoperatively, periodontal probing depths were found to be <=3 mm in both
      groups. Conclusions: PRF significantly reduced the AO incidence among smokers and
      had a positive effect on postoperative pain levels but not on periodontal
      healing.

PMID- 29465056
TI  - Effects of Inferior Alveolar Nerve Neurosensory Deficits on Quality of Life.
AB  - Objective: The purpose of this study was to investigate the effect of temporary
      or persistent neurosensory disturbance of the inferior alveolar nerve (IAN) on
      the quality of life using Oral Health Impact Profile (OHIP-14) questionnaire.
      Methods: The patients with the neurosensory deficit of the IAN that was confirmed
      by subjective and objective neurosensory tests formed the study group. The
      patients who had dental or oral and maxillofacial surgery procedures in the same
      unit and did not present neurosensory deficit were matched with the study group
      according to their gender and age and were presented as the control group. Both
      groups filled OHIP-14 questionnaire. Results: This study included 200 patients
      (122 female and 78 male), aged between 18 and 75 years. Kolmogrov-Smirnov,
      Levene, Mann-Whitney U, and Kruskal Wallis tests were used for statistical
      analysis. In study group, the average OHIP-14 scores were higher in women than in
      men in physical pain and handicap subgroups. There were significant differences
      between study and control groups in functional limitation, psychological
      discomfort, psychological disability, and handicap subgroups. The OHIP-14 scores
      were higher in study group compared with the control group. Conclusion: It was
      concluded that the patients with the neurosensory deficit of the IAN have a
      poorer quality of life than those without neurosensory deficits.

PMID- 29465057
TI  - The Role of Diffusion-Weighted Magnetic Resonance Imaging in the Differential
      Diagnosis of Simple and Hydatid Cysts of the Liver.
AB  - Introduction: The present study indicates that simple and hydatid cysts in liver
      are a common health problem in Turkey. The aim of the study is to differentiate
      different types of hydatid cysts from simple cysts by using diffusion-weighted
      images. Materials and Methods: In total, 37 hydatid cysts and 36 simple cysts in
      the liver were diagnosed. We retrospectively reviewed the medical records of the
      patients who had both ultrasonography and magnetic resonance imaging. We measured
      apparent diffusion coefficient (ADC) values of all the cysts and then compared
      the findings. Results: There was no statistically meaningful difference between
      the ADC values of simple cysts and type 1 hydatid cysts. However, for the other
      types of hydatid cysts, it is possible to differentiate hydatid cysts from simple
      cysts using the ADC values. Conclusion: Although in our study we cannot
      differentiate between type I hydatid cysts and simple cysts in the liver,
      diffusion-weighted images are very useful to differentiate different types of
      hydatid cysts from simple cysts using the ADC values.

PMID- 29465058
TI  - Beneficial Therapeutic Effects of Sildenafil on Bone Healing in Animals Treated
      with Bisphosphonate.
AB  - Objectives: The purpose of the present study was to evaluate the effects of
      sildenafil on mandibular fracture healing in animals treated with zoledronic acid
      by using histologic, histomorphometric, immunohistochemical, and
      radiodensitometric methods. Materials and Methods: A total of 36 Sprague-Dawley
      rats (3 months old) were used. All animals were treated intraperitoneally with
      0.1 mg/kg zoledronate three times per week, for a total of 8 weeks.
      Postoperatively, the animals were divided into two groups: zoledronate group (Z),
      which had no treatment applied (n = 18), and zoledronate + sildenafil (ZS), which
      were treated daily with 10 mg/kg sildenafil (n = 18). Each group was divided into
      two subgroups and the animals were sacrificed at the end of week 1 (Z1 and ZS1, n
      = 9) and week 4 (Z4 and ZS4, n = 9) after the operation. Histologic,
      histomorphometric, immunohistochemical analysis, and radiodensitometry were
      performed on the test subjects. Results: Sildenafil-treated groups showed a
      significant increase in fracture healing scores. This result was supported by the
      densitometric, histologic, histomorphometric, and immunohistochemical findings.
      Conclusions: Sildenafil may have positive effects on accelerating and improving
      fracture healing, and it may be used as a supporting factor in bone healing in
      patients treated with bisphosphonate (BP) to prevent negative effects of BP's.

PMID- 29465059
TI  - Efficiency of Lasers and a Desensitizer Agent on Dentin Hypersensitivity
      Treatment: A Clinical Study.
AB  - Aim: The aim of this clinical study was to determine and compare the efficiency
      of the glutaraldehyde-containing agent (GCA), Nd:YAG, Er,Cr:YSGG lasers, and the
      combination of them on the dentin hypersensitivity (DH) treatment. Subjects and
      Methods: This study was performed with the participation of 17 healthy adult
      patients having 100 teeth with DH; the patients were randomly divided into five
      groups according to the treatment protocol: (1) application of GCA on sensitive
      teeth, (2) Nd:YAG laser (1 W/cm2, 10 Hz) irradiation on sensitive teeth, (3)
      application of GCA on sensitive teeth and then Nd:YAG laser irradiation, (4)
      Er,Cr:YSGG laser (0.25 W/cm2, 20 Hz) irradiation on sensitive teeth, (5)
      application of GCA on sensitive teeth and then Er,Cr:YSGG laser irradiation.
      Sensitivity levels were assessed by the Yeaple probe on the buccal surfaces of
      the teeth at a force setting of 10 g. Measurements were performed for 30 min,
      after 7, 90, and 180 days of the therapy to assess the effects of
      desensitization. The evaluations were analyzed using the one-way analysis of
      variance and repeated measurement test (P < 0.05). Results: After sessions, DH
      was significantly reduced in all groups at each measurement point. The Er,Cr:YSGG
      laser with or without GCA application were the most effective ones in DH
      treatment (P < 0.05). Comparison of the treatment regimens demonstrated that the
      scores achieved with the Yeaple probe were not significantly higher for the
      Nd:YAG laser groups than the GCA alone group. Conclusions: This clinical study
      shows that the Er,Cr:YSGG laser have promising potential for the treatment of DH.

PMID- 29465060
TI  - Cyclic Fatigue Resistance of Novel Rotary Files Manufactured from Different
      Thermal Treated Nickel-Titanium Wires in Artificial Canals.
AB  - Aims: The aim of this in vitro study was to compare the static cyclic fatigue
      resistance of thermal treated rotary files with a conventional nickel-titanium
      (NiTi) rotary file. Subjects and Methods: Four groups of 60 rotary files with
      similar file dimensions, geometries, and motion were selected. Groups were set as
      HyFlex Group [controlled memory wire (CM-Wire)], ProfileVortex Group (M-Wire),
      Twisted File Group (R-Phase Wire), and OneShape Group (conventional NiTi wire)]
      and tested using a custom-made static cyclic fatigue testing apparatus. The
      fracture time and fragment length of the each file was also recorded. Statistical
      analysis was performed using one-way analysis of variance and Tukey's test at the
      95% confidence level (P = 0.05). Results: The HyFlex group had a significantly
      higher mean cyclic fatigue resistance than the other three groups (P < 0.001).
      The OneShape groups had the least fatigue resistance. Conclusions: CM-Wire alloy
      represented the best performance in cyclic fatigue resistance, and NiTi alloy in
      R-Phase had the second highest fatigue resistance. CM and R-Phase manufacturing
      technology processed to the conventional NiTi alloy enhance the cyclic fatigue
      resistance of files that have similar design and size. M-wire alloy did not show
      any superiority in cyclic fatigue resistance when compared with conventional NiTi
      wire.

PMID- 29465061
TI  - Evaluation of Brain Volume Changes by Magnetic Resonance Imaging in Obstructive
      Sleep Apnea Syndrome.
AB  - Background and Objectives: The objective of this study was to evaluate potential
      morphological changes in the brain tissue of patients with severe obstructive
      sleep apnea syndrome (OSAS) in comparison with normal subjects by using T1
      weighted magnetic resonance imaging (MRI) technique. Material and Methods: This
      study comprised subjects with severe OSAS with an apnea-hypopnea index (AHI) more
      than 30 and normal subjects with AHI less than 5 according to polysomnography
      findings. The study subjects were evaluated using Three Dimensional Magnetization
      Prepared Rapid Acquisition Gradient Echo sequence on T1-weighted MRI. FreeSurfer
      morphometric procedure was used as the automated segmentation method and in both
      cerebral and cerebellar hemsipheres and segmental volumes of brain were analyzed.
      Results: Of the 22 patients with severe OSAS, 19 were male, three were female and
      their ages ranged between 40 and 60 years (mean age 50.27 +/- 5.3 years). Of the
      22 control subjects 19 were male, three were female and their ages ranged between
      40 and 60 years (mean age 49.36 +/- 6.95 years). There were no statistically
      significant differences in terms of age and sex properties between the groups.
      There was a statistically significant difference in BMI between the OSAS patients
      and the control group. There were statistically significant differences in
      polysomnographic features (time elapsed below 90% SaO2 (min), Epworth Sleepiness
      Scale, AHI, mean minimum SaO2 (%), mean O2 desaturation (%), and arousal index
      values) between the OSAS patients and the control group. Conclusions: The
      findings of our study indicated that even if severe, no structural changes occur
      in the course of mild, moderate, and severe OSAS.

PMID- 29465062
TI  - Microleakage of Different Adhesive Systems in Primary Molars Prepared by Er: YAG
      Laser or bur.
AB  - Background and aim: This study aimed to examine the microleakage of class V
      cavities of primary molars prepared by either a conventional dental bur or Er:YAG
      laser and one of two different adhesive systems. Methods: A total of 50 tooth
      samples from primary molars were used in this study. They were randomly assigned
      into five experimental groups of 10 samples each, according to the cavity
      preparation technique and the type of adhesive system applied to the cavities.
      Following cavity preparation, etching, bonding, and filling steps, samples were
      dyed using basic fuchsine and were sectioned longitudinally in buccolingual
      direction. Percentages of dye penetration at gingival and occlusal margins were
      calculated for each group. Results: Overall, microleakage scores of gingival
      margins were significantly higher than those of occlusal margins (P < 0.001). The
      group that underwent laser preparation, laser etch, and self-etch bonding
      procedures had worse microleakage scores for gingival margins. However, all
      groups had similar occlusal scores (P > 0.05). Conclusion: Self-etch bonding
      systems and cavity preparation with Er:YAG laser may be an alternative to
      conventional restoration of primary molars with compomers. Further studies are
      warranted to fully elucidate the effect of laser-based etching techniques in
      cavities prepared by laser.

PMID- 29465063
TI  - Posterior Reversible Encephalopathy Syndrome in the Emergency Service.
AB  - Posterior reversible encephalopathy syndrome (PRES) is an entity characterized by
      headache, altered mental status, seizures, visual disturbances, and focal
      neurological signs. The most common etiologies of PRES are hypertension and renal
      failure, and the most frequent pathophysiology is hyperperfusion. PRES is
      generally symmetrical, often in the occipital and parietal lobes, and is
      typically characterized by vasogenic edema in the subcortical white matter. This
      study involves a 38-year-old female patient who had hypertension, used
      immunosuppressive drugs and was also found to have nephropathy. After 3 months of
      treatment for PRES, the patient's symptoms had declined.

PMID- 29465064
TI  - Surgical Management of a Bilateral Bifid Condyle: Diagnosis, Three-dimensional
      Reconstruction, and Treatment - A Report of a Case and Review of the Literature.
AB  - Bifid condyle is a rare entity with a difficult diagnosis and usually identified
      as an incidental finding on routine radiographic examination. The etiology is not
      well known, possible causes may be developmental, traumatic, vascular, abnormal
      muscle pulling, nutritional, endocrinal, teratogenic, and infections. The
      orientation of the condylar heads can behelpful for the etiological
      diagnosis.This case report describes a 56-year-old woman who suffered from a
      unilateral, progressively increasing, radiating pain which intensified with the
      movement of the mandible and includes information about the diagnosis,
      management, radiographic and three-dimensional model features and review of the
      literature.

PMID- 29465065
TI  - Use of ECDC PPS HAI&AU data to evaluate adherence to national guidelines for
      antimicrobial treatment of community--acquired pneumonia
AB  - INTRODUCTION    Point prevalence surveys are widely described as a useful tool
      for evaluating antimicrobial policy and adherence to guidelines. OBJECTIVES    We
      aimed to investigate if data from the European Centre for Disease Prevention and
      Control (ECDC) point prevalence survey of healthcare-associated infections and
      antimicrobial use (PPS HAI&AU) canbe used to evaluate adherence to national
      guidelines for the treatment of community-acquired pneumonia (CAP) and to analyze
      the quality of treatment regimens. PATIENTS AND METHODS    Data for 72 698
      patients were collected in Poland between the years 2012 and 2015 according to
      the ECDC Protocol v.4.2. CAP was an indication for antimicrobial treatment in
      3608patients. Patients hospitalized longer than 48 hours were excluded. A total
      of 667 patients met the inclusion criteria, and 79 regimens were recorded and
      evaluated as concordant or discordant with the guidelines. Afterwards, 7 experts
      scored the regimens from 1 to 5. The averages were calculated, and the results
      below 3.0 were considered as not optimal and those of 3.0 or higher-as optimal.
      Coherence of the experts' scores was evaluated. RESULTS    Of all patients, 153
      (22.8%) were treated exactly according to the guidelines. Nineteen regimens
      (24.0%) were optimal but discordant with the guidelines; they were administered
      to 346 patients (51.9%). The remaining 50 regimens (63.3%) were evaluated as
      discordant and not optimal and were used in 169 patients(25.3%). The correlation
      results of the experts' scores were significant. CONCLUSIONS    ECDC PPS HAI&AU
      data can be efficiently used to assess adherence to guidelines. Despite low
      adherence (22.8%), almost 75% of patients received optimal antimicrobial
      treatments. Actions promoting the guidelines and time-series studies analyzing
      improvement of adherence should be considered.

PMID- 29465066
TI  - Prognostic utility of the N terminal prohormone of brain natriuretic peptide and
      the modified Model for End Stage Liver Disease in patients with end stage heart
      failure.
AB  - INTRODUCTION    The N terminal prohormone of brain natriuretic peptide (NT
      proBNP) is secreted by cardiomyocytes in response to increased wall stress
      resulting from pressure and volume overload. The modified Model for End Stage
      Liver Disease (modMELD) scale reflects the systemic effect of heart failure (HF),
      which includes end-organ congestion and subsequent hepatic and renal dysfunction.
      OBJECTIVES    The aim of this study was to assess the prognostic accuracy of NT
      proBNP and the modMELD score, as well as to compare their usefulness in the risk
      stratification of patients with end-stage HF awaiting orthotopic heart
      transplantation (OHT). PATIENTS AND METHODS    We retrospectively analyzed the
      data of 641 consecutive adult patients awaiting OHT between 2012 and 2016.
      Exclusion criteria included "urgent status", OHT, and removal from the waiting
      list. Clinical and laboratory data were obtained at the time of admission to the
      waiting list. The primary endpoint was all-cause mortality during a one-year
      follow up. RESULTS    In the overall population of 370 patients, the median age
      was 54.0 (46.0-60.0) years, and 87.6% of the patients were male. During the
      follow-up period, the mortality rate was 27.6%. The areas under the curve (AUCs)
      were 0.619 (95% CI: 0.557-0.681) for NT proBNP and 0.870 (95% CI: 0.833-0.906)
      for modMELD. The difference between the AUC for modMELD and NT proBNP was 0.251
      (95% CI: 0.179-0.322, P <0.0001). CONCLUSIONS    The usefulness of NT proBNP in
      evaluating the prognosis of patients with end stage HF awaiting OHT is limited.
      The modMELD score is a better prognostic marker of waiting list mortality than
      the NT proBNP serum concentration.

PMID- 29465067
TI  - Preliminary Study of the Role F-Box Protein 32 (FBXO32) in Colorectal Neoplasms
      Through the Transforming Growth Factor beta (TGF-beta)/Smad4 Signalling Pathway.
AB  - BACKGROUND F-box protein 32 (FBXO32) (also known as atrogin-1), a member of the F
      box protein family, was recently shown to be a transforming growth factor beta
      (TGF-beta)/Smad4 target gene involved in regulating cell survival. It can be
      transcriptionally silenced by epigenetic mechanisms in some cancers, but its role
      in colorectal carcinoma (CRC) is unclear. We investigated the role of FBXO32 in
      CRC and determined its prognostic significance. MATERIAL AND METHODS We used real
      time quantitative PCR, Western blot, and immunohistochemistry to elucidate the
      role of FBXO32 in clinical specimens and primary CRC cell lines. Differences in
      patient survival were determined by the Kaplan-Meier method and log-rank test.
      RESULTS We found that the FBXO32 and SMAD4 levels were higher in normal tissues
      than in CRC tissues, but PAI-1 and VEGF levels showed the opposite pattern. The
      expressions of FBXO32 and SMAD4 were related to clinicopathological parameters in
      CRC. Kaplan-Meier analyses showed that the 5-year overall survival of the low
      FBXO32 expression group was significantly shorter than that of the high-FBXO32
      expression group (p=0.010). CONCLUSIONS The fbxo32 gene is a novel tumor
      suppressor that inhibits CRC progression by inducing differentiation. Elevated
      expression of FBXO32 predicts longer survival in CRC patients.

PMID- 29465068
TI  - [Human resources provision for maxillofacial surgery facilities].
AB  - The aim of the study was to analyze the key trends of medical staff provision for
      maxillofacial surgery facilities. It is established that the provision of the
      population with maxillofacial surgeons staff has slightly decreased from 0.08
      (year 2011) to 0.06 (year 2015). The amount of staff positions at this period has
      increased by 17.22%, the intensity of growth of employed positions has grown by
      15.74%, which makes the understaffing rate equal to approximately 8-10%. The
      coefficient of part-time workers has also varied slightly from 1.4 in 2011 to
      1.26 in 2015. Over 93% of maxillofacial surgeons work in hospitals. The
      qualification category was awarded to over 46.0% of specialists in this field,
      97.6% of maxillofacial surgeons have a specialist certificate. The results
      indicate the need for a new project of personnel policy strategy for further
      training and professional growth of maxillofacial surgeons.

PMID- 29465069
TI  - [Analysis of the prevalence of dental diseases requiring prosthodontic treatment
      among the rural population of the Omsk region].
AB  - The aim of the study was to evaluate the prevalence of dental diseases requiring
      prosthetic treatment among rural population of Omsk region. The study involved
      1247 residents from 12 rural areas of the Omsk region at the age of 18 to 87
      years. Partial absence of teeth was found in 69.4+/-1.30%, 7.5+/-0.75% had a
      complete absence of teeth on one jaw and 3.8+/-0.54% on both jaws. Malocclusion
      is present in 29.5+/-1.29% of rural residents, the pathology of dental hard
      tissues, clinical symptoms of TMJ dysfunction, increased dental abrasion were
      revealed in 63.8+/-1.36%, 12.0+/-0.92% and 8.7+/-0.80%, respectively. Thus the
      study showed high prevalence of dental pathology that require prosthetic dental
      rehabilitation in rural areas of the Omsk region.

PMID- 29465070
TI  - [Root canals dentinal wall structure after photodynamic exposure].
AB  - The aim of the study was to assess root canal dentinal walls structure after
      photodynamic exposure with the use of 0.5% photoditazine. A root canal dentin of
      46 single root intact teeth removed for orthodontic indications was examined by
      scanning electron microscope JEOL JSM-6510 (Japan). Microphotographs of the root
      canal wall were obtained in the orifice, central and apical parts under*2000
      magnification. It was found that photoactivation of 0.5% gel photoditazine by a
      light source, laser or diode, with a wavelength of 635-660 nm and a power of 150
      200 mW is an effective technique for removing the smear layer of the root canal
      wall, which facilitates the maximum opening of the dentinal tubules to a depth of
      2-3 MUm. The best result (the maximum number of open dentinal tubules, the
      absence of a smear layer) is observed with 3 min photoditazine exposure and 2 min
      of laser exposure. The method can be proposed as an alternative supplement to the
      conventional root canals irrigation.

PMID- 29465071
TI  - [Morphological evaluation of singlet phototherapy in the treatment of periodontal
      diseases in an experimental study].
AB  - The aim of the study was to compare the effectiveness of laser singlet
      phototherapy and traditional photodynamic therapy the treatment of periodontal
      diseases in an animal model. The experimental model involved 70 male rats Wistar
      in which periodontitis was modeled and treated: in group I (30 animals) a
      nanosecond laser device for medical use with a wavelength of 1270 nm was used for
      7 sessions in a 400 ns pulse mode, an average radiation power of 2 W, and a
      radiation density of 200 J/cm2, group II (30 animals) received photodynamic
      therapy with the administration of a photosensitizer, followed by irradiation
      with a laser wavelength of 660 nm for 7 sessions 2 Wt average radiation power,
      group III (controls, 10 animals) - traditional drug therapy. Morphological
      studies were performed on 7, 14 and 21 day after treatment. On day 7th and 14th
      the study revealed In group I the presence of full blood vessels and diffuse
      expressed leukocyte infiltration with an admixture of macrophages, in group II -
      pronounced edema of the tissue and vasoconstriction. On day 21 the picture
      included in group I regenerated periodontal ligament with dilated full blood
      vessels on the border with the bone beams of the alveolar bone, in group II a
      moderately pronounced edema of the periodontal ligament with single dilated
      vessels, in controls significantly destroyed periodontal ligament substituted
      with granulation tissue and periodontal ligament. Thus, the treatment of
      periodontitis with the methods of singlet phototherapy leads to the development
      of reactive inflammation and significant vascularization of periodontal tissues
      which contributes to the rapid regeneration and stability of remission.

PMID- 29465072
TI  - [Rationale for the application of surface-enhanced Raman scattering for
      identification of main pathogens of purulent-inflammatory diseases in
      maxillofacial area].
AB  - The objective of the research was to elaborate experimental-theoretical and
      clinic-bacteriological rationale for the application of laser diagnostic for
      identification of main pathogens of purulent-inflammatory processes in
      maxillofacial area. For germs identification by giant Raman scattering effect
      SERS-substrate with nano silver metallic balls, reference strains (Ps. aeruginosa
      27853 and S. aureus 25923) and clinical cultures of Staphylococcus, Bacillus and
      Escherichia coli were used. Using an example of purulent inflammation pathogens
      we considered that each of bacterial species is characterized by individual
      spectral lines of Raman scattering, which allows to identify them in short term
      (1-2 min). Moreover the proposed method is highly sensitive (105-106 CFU/ml).
      Creation of germs library and device portability makes use of laser diagnostic
      for express-indication purulent infections possible directly in clinical
      conditions. Thus, analytical capability, quick result, high sensitivity and
      peculiarity, economical effectiveness due to lack of necessity to use growth
      medium and to transport it to microbiological lab gives an opportunity to
      consider laser diagnostic as a perspective universal express-method of clinical
      microbiology.

PMID- 29465073
TI  - [Increasing the effectiveness of mandibular molars root resection surgery using
      retrograde endodontic revision].
AB  - The purpose of the present study was to increase the effectiveness of mandibular
      molars apical root resection surgery. The study included 21 patients with
      diagnosis 'persistent apical periodontitis', 'root cyst', in 11 cases surgery was
      performed with less traumatic access with piezoelectric surgery system for
      separation of cortical bone block and subsequent reposition after resection and
      retrograde root filling. The planning and procedure was described by 2 clinical
      cases. Bone block reposition surgical procedure showed clinical effectiveness and
      was considered as a most acceptable technique of root resection.

PMID- 29465074
TI  - [Diagnostic value of optical coherence tomography for oral leukoplakia
      assessment].
AB  - The article presents a comparative analysis of the results of in vivo scanning of
      oral mucosa leukoplakia with optical coherence tomography (OCT) method and
      pathological studies in 15 patients (9 females and 6 males aged 27-82). The study
      revealed specific OCT signs of leukoplakia: even disorder of tissue layering and
      less clear visualization of lamina propria. OCT is an important stage in the
      differential diagnosis of leukoplakia of the oral mucosa and significantly
      complements the clinical and pathomorphological study.

PMID- 29465075
TI  - [Resorbable vs nonresorbable fixation in alveolar bone grafting in unilateral
      cleft lip and palate patients].
AB  - The aim of the study was to evaluate the resorbable vs nonresorbable fixation
      efficiency in bone grafting for unilateral cleft lip and palate (UCLP) patients.
      Thirty eight UCLP patients aged from 7 to 17 years (mean 11.5+/-3.1 years) were
      divided in two groups with different types of cortical graft fixation: group 1 ?
      titanium screws (22 patients), group 2 ? resorbable pins (16 patients). The
      Bergland and Chelsea scales were used to evaluate the outcomes 8 months after
      surgery. Additional authors' original scales were introduced: bone volume scale
      and pyriform rim restoration scale. The Bergland and Chelsea scales have shown
      good results in groups 1 and 2 in 91 and 81% of cases, satisfactory in 4.5 and
      19% of cases, respectively. Upon the bone volume scale good results were achieved
      in groups 1 and 2 in 64 and in 75% of cases, satisfactory results - in 18 and 19%
      of cases, respectively. Upon the pyriform rim restoration scale good results
      achieved in 59 and 88% of cases, respectively. We also took into consideration
      the influence of age, diagnosis, post-op complications. No statistically
      significant difference between groups was found, with neither age nor diagnosis
      showing any influence. Only postsurgical complications and the stability of the
      orthodontic design seem to be important for good bone formation after alveolar
      bone grafting.

PMID- 29465076
TI  - [The study results of the alveolar ridge mucosal microcirculation after bone
      augmentation using the Tunnel Technique method].
AB  - It reports the results of primary basal blood flow in partially edentulous bone
      tissue with atrophy, as well as comparative evaluation of haemomicrocirculation
      level of the alveolar bone mucosa after bone augmentation via tunneling and
      conventional methods. The results of the initial state of microcirculation in the
      mucous membrane of the alveolar process in the partially edentulous area show a
      45% decrease of blood flow (M), its intensity (s) by 60%. Microcirculatory shifts
      in blood flow levels indicators, its intensity, vasomotor activity are more
      evident when using the conventional method, where revascularization takes more
      than five months. When using the tunnel method, there is an improvement in
      haemodynamic mechanisms of tissue blood flow regulation. Microcirculation is
      restored 4 months after surgery.

PMID- 29465077
TI  - [Changes of postural statusa in patients undergoing orthodontic treatment].
AB  - The study objective was to determinate variations of stato-dynamical functional
      markers of postural balance system in the process of malocclusion treatment.
      Twenty patients aged from 14 to 30 years with class II malocclusion were
      recruited for this prospective study. All patients underwent electromyography of
      mm. temporalis and mm. maseter in rest and at maximal jaws pressure. Postural
      balance was evaluated by stabilometry platform and body's regions relationship
      was assessed by computer optical topography. Orthodontic interventions included
      using occlusal splint, dental straps or 'TwinForce' device. There were two
      diagnostic sessions: before and after one month of orthodontic treatment. The
      majority of patients after anterior dislocation of mandible demonstrated
      significant increase in unilateral masticatory muscles activity (r<0.05) which
      correlated with iliac crest position. According to computerized topography data
      superior iliac crest position was registered in opposite side with regard to
      muscle hypertonia. According to stabilometry data forward translation of the
      mandible resulted in retroversion of total pressure point projection (r<0.05).
      Asymmetric muscle working in the process of occlusal adjustment may provoke
      postural imbalance in distal body regions. It dictates postural system condition
      monitoring during orthodontic treatment.

PMID- 29465078
TI  - [Prosthodontic treatment of edentulous patients with postoperative mandibular
      defects of oncological origin].
AB  - The aim of the study was clinical and bacteriological approbation of improved
      obturator dentures with soft lining. The study involved 116 patients (68 females
      and 48 males aged 47-78) with edentulous jaws and side palatal defect of
      oncological origin. Improved elastic obturator maxilla dentures in patients with
      palatal defects proved to have better stability and provides better comfort
      effectively preventing inflammation of prosthetic bed soft tissues.

PMID- 29465079
TI  - [Orthodontic treatment of malocclusion Class III in patients aged 6-12 by
      Postnikov appliance, face mask and bracket system].
AB  - The diagnostics and treatment of malocclusion Class III in patients aged 6-12 is
      an vital problem in orthodontics. Method of orthodontic treatment of malocclusion
      Class III in patients with the help of improved and patented orthodontic
      construction - 'Postnikov appliance' - and face mask and bracket system is
      analysed in the article. Orthodontic treatment of malocclusion Class III was
      examined in 24 patients aged 6-12 by the suggested method. All patients were
      examined clinically and with the help af additional diagnostic methods: head
      cephalometry in lateral position with further data analysis in Dolphin Imaging
      (USA). The use of computer technologies in Dolphin Imaging helps to controll the
      process of correction of dentition correlation in different stages of treatment,
      to reduce the period of treatment of malocclusion Class III in patients aged 6-12
      and to improve face esthetics and life quality ratio.

PMID- 29465080
TI  - [Bifid mandibular canal].
AB  - The article describes three types of bifurcations of the mandibular canal that
      were identified as accidental findings in cone-beam computed tomograms of the
      maxillofacial area of patients subjected to dental treatment. Bifid mandibular
      canal types are illustraded with clinical cases.

PMID- 29465081
TI  - [Radiation-associated changes in salivation of patients with cancer of
      maxillofacial region].
AB  - The radiation has an antitumor effect and causes radiation reactions and damage
      to surrounding tissues within the framework of combined antitumor treatment of
      patients with cancer of maxillofacial region. It also has an irreversible effect
      on the production of saliva by large and small salivary glands, and this must be
      taken into account when planning radiation therapy for this group of patients.

PMID- 29465082
TI  - Author Correction: Amazonian forest-savanna bistability and human impact.
AB  - This corrects the article DOI: 10.1038/ncomms15519.

PMID- 29465083
TI  - Retraction: A significant causal association between C-reactive protein levels
      and schizophrenia.
AB  - This retracts the article DOI: 10.1038/srep26105.

PMID- 29465084
TI  - Protein kinase D1 regulates subcellular localisation and metastatic function of
      metastasis-associated protein 1.
AB  - BACKGROUND: Cancer progression and metastasis is profoundly influenced by protein
      kinase D1 (PKD1) and metastasis-associated protein 1 (MTA1) in addition to other
      pathways. However, the nature of regulatory relationship between the PKD1 and
      MTA1, and its resulting impact on cancer metastasis remains unknown. Here we
      present evidence to establish that PKD1 is an upstream regulatory kinase of MTA1.
      METHODS: Protein and mRNA expression of MTA1 in PKD1-overexpressing cells were
      determined using western blotting and reverse-transcription quantitative real
      time PCR. Immunoprecipitation and proximity ligation assay (PLA) were used to
      determine the interaction between PKD1 and MTA1. PKD1-mediated nucleo-cytoplasmic
      export and polyubiquitin-dependent proteosomal degradation was determined using
      immunostaining. The correlation between PKD1 and MTA1 was determined using intra
      tibial, subcutaneous xenograft, PTEN-knockout (PTEN-KO) and transgenic
      adenocarcinoma of mouse prostate (TRAMP) mouse models, as well as human cancer
      tissues. RESULTS: We found that MTA1 is a PKD1-interacting substrate, and that
      PKD1 phosphorylates MTA1, supports its nucleus-to-cytoplasmic redistribution and
      utilises its N-terminal and kinase domains to effectively inhibit the levels of
      MTA1 via polyubiquitin-dependent proteosomal degradation. PKD1-mediated
      downregulation of MTA1 was accompanied by a significant suppression of prostate
      cancer progression and metastasis in physiologically relevant spontaneous tumour
      models. Accordingly, progression of human prostate tumours to increased
      invasiveness was also accompanied by decreased and increased levels of PKD1 and
      MTA1, respectively. CONCLUSIONS: Overall, this study, for the first time,
      establishes that PKD1 is an upstream regulatory kinase of MTA1 status and its
      associated metastatic activity, and that the PKD1-MTA1 axis could be targeted for
      anti-cancer strategies.

PMID- 29465085
TI  - Protein kinase D1: gatekeeper of the epithelial phenotype and key regulator of
      cancer metastasis?

PMID- 29465086
TI  - [Anticoagulation for continuous renal replacement therapyin critically ill
      patients].

PMID- 29465087
TI  - [Control of cross-contamination in dental prostheses laboratories in Galicia].
AB  - BACKGROUND: Dental laboratories are a potential source of cross-contamination.
      This study aims to assess its control in Galicia. METHODS: Voluntary random
      telephone interviews resulted in 149 completed questionnaires. The variables are
      described by percentages or means and standard deviations. A bivariate analysis
      was undertaken using the Chi square test. RESULTS: Participants were mostly
      middle-age (mean=45.7, SD=9.8) males (68.5%) with 20.8 (SD=10.5) years of
      professional experience in middle-size urban (58.4%) laboratories, who identified
      a higher risk when receiving items from the clinic (80.6%). Most technicians
      (57.7%) have a written protocol. Many (55.0%), significantly older males, do not
      check for item disinfection. Most technicians use gloves (62.4%) particularly
      younger staff at larger laboratories. Fifty-five point seven percent had been
      vaccinated against hepatitis B. Only 22.0% of technicians reported receiving
      training in cross-contamination control. CONCLUSIONS: Identified cross-infection
      control practices are below standards, and lack of training and protocols are a
      matter for concern.

PMID- 29465088
TI  - [The problem of hidden HIV infection].

PMID- 29465089
TI  - [Combined thorax-abdomen extraction in a Maastricht type III donor].
AB  - Donation after circulatory death (Maastricht type III donation) or controlled
      cardiac death refers to the retrieval of organs for transplantation purposes
      following death confirmed using circulatory criteria after the withdrawal of life
      support. The persistent shortfall in organ availability has prompted the
      development of donation programs following circulatory death for lung
      transplantation. The combined thorax-abdomen extraction in these cases is carried
      out in only twelve centres in Spain, while the combined use of abdominal
      normothermic regional perfusion (NRP) is even more exceptional. The first case of
      pulmonary and abdominal extraction in a Maastricht type III donor in Navarre with
      this type of preservation techniques is a milestone and the success achieved
      shows that it is a feasible and safe procedure.

PMID- 29465090
TI  - [Level of knowledge of Quality Commitment Campaign and of "do not do"
      recommendations amongst general practitioners, pediatricians and nurses Primary
      Care].
AB  - BACKGROUND: To evaluate if the Quality Commitment Campaign (QCC) was sufficiently
      known among primary care professionals (PC), and second, to evaluate the
      knowledge about certain recommendations of what should not be done in PC.
      METHODS: A observational study was conducted. General practitioners (GP),
      pediatricians (PED) and nursing (NUR) participated. A direct question was asked
      about whether QCC was known and a set of dichotomous questions based on the "do
      not do" recommendations to assess their knowledge. A sample size of 288
      professionals from each group was the minimum required for a sampling error of
      5%, 95% confidence level and p=0.75. The field study was conducted with the
      collaboration of health services and professional and scientific organizations.
      Data were described by frequencies and mean (standard deviation), and compared by
      means of ?2/Fisher or ANOVA and t-test. RESULTS: A total of 1,904 professionals
      (936 GP, 682 PED and 286 NUR) answered. The QCC initiative was known by 828
      (43.5%) professionals: 524 (56.0%) GP, 234 (34.3%) PED and 70 (24.5%) NUR
      (p<0.001). All the questions were correctly answered by 652 (69.7%) GP, 631
      (92.5%) PED and 116 (40.6%) NUR. Significantly more mistakes (p<0.001) were made
      by those who did not know the QCC, worked in the private sector or were not
      considered responsible for overuse. Despite not knowing the QCC, 60% GP and 90%
      PED answered all the questions of the test correctly. CONCLUSIONS: NUR and GP
      could benefit from a greater diffusion of the QCC. As could those working in the
      private sector and those who believe that professionals have little
      responsibility for unnecessary overuse.

PMID- 29465091
TI  - [Public participation in health. A review of reviews].
AB  - BACKGROUND: This study aims to synthesize knowledge about the role of the
      public's participation in the definition, prioritization, rationalization,
      monitoring or control of policies, plans, governance, investment/disinvestment,
      and design of health services. METHODS: Review of review articles (narrative or
      systematic) about consumer participation indexed in PubMed until August 2016.
      RESULTS: Forty-two reviews were identified (eighteen systematic and twenty-four
      narrative). The extent of participation was provincial/regional or national. The
      issues addressed covered: What is public participation? What benefits are
      expected? Who participates in the representation of citizens? How and to what
      extent do citizens participate and with what outcomes? The impact of public
      participation has hardly been studied. CONCLUSIONS: There is moderate evidence in
      support of the argument that public participation legitimizes decisions of the
      Health Authorities, and improves outcomes of health policies. There is consensus
      on how participation techniques should be applied but there is a need to inquire
      more deeply into the level of impact of this participation.

PMID- 29465092
TI  - [Need for a holistic and quantitative approach for diagnosing and improving
      hospital emergency services].

PMID- 29465093
TI  - [Perceptions of health care professionals about end-of-life care, obstacles and
      ethical dilemmas in hospitals, primary care and nursing homes.]
AB  - BACKGROUND: This study compares the perceptions of physicians and nurses
      regarding professional practice, perceived obstacles and ethical dilemmas in end
      of-life care in primary care (PC), hospitals and nursing homes (NH). METHODS:
      Descriptive, cross-sectional and multicentre study. Intentional sampling of
      physicians and nurses with more than four months professional practice from four
      hospitals, five PC centres and twenty-nine NH in Granada was carried out. An ad
      hoc questionnaire was developed to assess perception of professional practice in
      eight dimensions (structure and processes of care, physical, psychological,
      social, spiritual, cultural, ethical aspects and care for the dying), frequency
      of ethical dilemmas, and obstacles to optimum care. Scores of different settings
      were compared using the ANOVA test and post hoc analysis. RESULTS: A total of 378
      professionals participated, 215 (56.9%) from hospitals, 97 (25.7%) from PC and 66
      (17.5%) from NH. NH professionals were older and had more professional experience
      than those from PC and hospitals, and they also rated both the institution and
      their own professional practice significantly better (p<0.01) than other
      professionals with respect to the dimensions of structure and processes of care,
      physical, psychological, social, spiritual, cultural aspects and care for the
      dying. Psychological and ethical aspects were the worst valued in all settings,
      with no differences regarding ethical aspects. Fewer ethical dilemmas were
      identified by PC professionals, while NH professionals perceived greater
      obstacles to end-of-life care in relation to other settings. CONCLUSION: Primary
      care and hospitalization presented similar results on the perception of end-of
      life care, and lower results than those of nursing homes, although in these
      centres more ethical dilemmas and more obstacles were identified.

PMID- 29465094
TI  - How can I help? Improving the effectiveness of communication in hospitals for
      people with communication difficulties.

PMID- 29465095
TI  - Cutaneous melanoma: an updated SIGN Guideline.

PMID- 29465096
TI  - Management of acute upper gastrointestinal bleeding: an update for the general
      physician.
AB  - Acute upper gastrointestinal bleed (AUGIB) is one of the most common medical
      emergencies in the UK, with roughly one presentation every 6 min. Despite
      advances in therapeutics and endoscopy provision, mortality following AUGIB over
      the last two decades has remained high, with over 9,000 deaths annually in the
      UK; consequently, several national bodies have published UK-relevant guidelines.
      Despite this, the 2015 UK National Confidential Enquiry into Patient Outcome and
      Death in AUGIB highlighted variations in practice, raised concerns regarding
      suboptimal patient care and released a series of recommendations. This review
      paper incorporates the latest available evidence and UK-relevant guidelines to
      summarise the optimal pre-endoscopic, endoscopic, and post-endoscopic approach to
      and management of non-variceal and variceal AUGIB that will be of practical value
      to both general physicians and gastroenterologists.

PMID- 29465097
TI  - Quantitative data analysis of perceived barriers and motivators to physical
      activity in stroke survivors.
AB  - BACKGROUND: Levels of physical activity after stroke are low, despite multiple
      health benefits. We explored stroke survivors' perceived barriers, motivators,
      self-efficacy and intention to physical activity. METHODS: Fifty independently
      mobile stroke survivors were recruited prior to hospital discharge. Participants
      rated nine possible motivators and four possible barriers based on the Mutrie
      Scale, as having 'no influence', 'some influence' or 'a major influence' on
      physical activity. Participants also rated their self-efficacy and intention to
      increasing walking. RESULTS: The most common motivator was 'physical activity is
      good for health' [34 (68%)]. The most common barrier was 'feeling too tired' [24
      (48%)]. Intention and self-efficacy were high. Self-efficacy was graded as either
      4 or 5 (highly confident) on a five-point scale by [34 (68%)] participants, while
      42 (84%) 'strongly agreed' or 'agreed' that they intended to increase their
      walking. CONCLUSION: Participants felt capable of increasing physical activity
      but fatigue was often perceived as a barrier to physical activity. This needs to
      be considered when encouraging stroke survivors to be more active.

PMID- 29465098
TI  - Effect of reinforced audit and feedback intervention on physician behaviour: a
      multifaceted strategy for targeting medical record documentation.
AB  - We investigated the effects of reinforced audit and feedback on the medical
      record documentation (MRD) of 35 surgical residents at a tertiary university
      hospital. In three phases (pre-intervention, 3 and 9-month post-intervention),
      525 medical records were assessed. An educational guideline assisting residents
      to record more accurate MRD was developed. The MRD rate in the pre-intervention
      and immediate post-intervention phases had changed significantly. The MRD rate in
      the pre-intervention and 9 months after cessation of intervention was not
      statistically significant. Reinforced audit and feedback had only a short term
      effect on MRD. To achieve long lasting change, we suggest residents' MRD
      behaviour must be integrated in their periodic clinical performance evaluation
      and reinforced through positive feedback including incentive mechanisms.

PMID- 29465099
TI  - Is it safe to use gadolinium-based contrast agents in MRI?
AB  - Gadolinium-based contrast agents have greatly expanded the capability of magnetic
      resonance imaging and have been used extensively in neuroradiology over the past
      30 years. When initially developed they were thought to be relatively harmless;
      it was later discovered they are associated with nephrogenic systemic fibrosis
      and should be used with caution in certain patient groups, especially those with
      renal failure. Lately it has been found that the use of these contrast agents may
      result in deposition of gadolinium in the brain even in patients with an intact
      blood-brain barrier. While this has not been shown to be associated with any
      clinical effects, a precautionary approach has been advised by the regulatory
      authorities. Here we review the development of the gadolinium contrast agents,
      their use and the advice related to this new information.

PMID- 29465100
TI  - Central diabetes insipidus unmasked by corticosteroid therapy for cerebral
      metastases: beware the case with pituitary involvement and hypopituitarism.
AB  - Patients with intra-cerebral metastases often receive glucocorticoids,
      particularly in the presence of peri-lesional vasogenic cerebral oedema. We
      present a case of presumptive lung carcinoma with cerebral metastases where
      central diabetes insipidus was unmasked after glucocorticoid administration and
      correction of undiagnosed central hypocortisolism.

PMID- 29465101
TI  - Tocilizumab, an interleukin-6 inhibitor: a steroid sparing agent in giant cell
      arteritis.

PMID- 29465102
TI  - Non-invasive electrical brain stimulation as a treatment for depression.

PMID- 29465103
TI  - The growing role of the JRCPTB and Federation in international postgraduate
      physician education and training.

PMID- 29465104
TI  - Patients and consumers.
AB  - Successive governments of the UK have strongly supported two policies: an NHS
      free at the point of delivery, and the encouragement of consumer choice. It was
      natural for governments to think that amalgamating the policies would increase
      patient satisfaction, improve efficiency and save money. There are many reasons
      why this has not been well-received by patients and doctors and has not saved
      money, but the underlying problem is that there is a conceptual misfit between
      healthcare as public policy and as individual responsibility. Patients in the NHS
      cannot become consumers and doctors cannot become suppliers of goods and
      services.

PMID- 29465105
TI  - Communicating with a human voice: developing a relational model of empathy.
AB  - The medical profession has adopted a cognitive model of empathy, or detached
      concern, in its professionalism and practice. As a consequence there is now an
      empathy gap which has been demonstrated by lapses in patient care in the UK.
      There may also be an empathy gap developing in medical students during their
      training. This paper argues for the adoption of a relational view of empathy
      which embraces emotional and moral dimensions of the concept, acknowledges the
      importance of the clinical context and prioritises the relationship between the
      doctor and patient. A relational model extends to encompass the patient's family
      and all members of the healthcare team. By exploring the process of empathising
      in clinical practice I develop a relational model that is more appropriate for
      modern patterns of patient care and medical education than detached concern.
      Adoption of a relational model of empathy in training and practice can help
      bridge the empathy gap.

PMID- 29465106
TI  - MRI brain white matter change: spectrum of change - how we can grade?
AB  - Magnetic resonance imaging has become a widely used clinical tool for the
      assessment of neurologic symptoms, as well as being increasingly used in
      neuroscience research. White matter hyperintensities are common findings on brain
      imaging and their discovery leads to questions about best management, especially
      when findings are incidental or not considered relevant to the patient's
      presentation. This review will discuss the varied causes of white matter
      hyperintensities, consider how best to distinguish between them radiologically,
      and when they might have potential clinical relevance.

PMID- 29465107
TI  - Sanatoria revisited: sunlight and health.
AB  - Since the 18th century tuberculosis has been a major cause of death throughout
      the world. It is a highly infectious disease that spreads by droplet infection
      and finding effective treatment to combat tuberculosis took a great deal of time.
      One of the first treatments to have some real success was a stay in a sanatorium.
      Sanatoria were homes that provided patients with good food and fresh air (and
      therefore sunlight). The first sanatorium to use sunlight therapy (heliotherapy)
      seriously was founded in Leysin, Switzerland, by Auguste Rollier. Patients built
      up their sun exposure gradually to prevent sunburn or skin damage. We suggest
      that heliotherapy was more successful in treating tuberculosis than was
      appreciated once chemotherapy became available. The birth of heliotherapy
      coincided with an increased appreciation of the association of sunlight and
      health among the general public. The secret of its success is the combined
      effects of sunlight on the skin inducing the production of nitric oxide and
      vitamin. Nitric oxide is not only a messenger in the cardiovascular system and
      responsible for relaxation of vascular muscle but is also involved in the innate
      immune system. Vitamin D is responsible for immune system functions and multiple
      studies have found an association between tuberculosis immunity and high vitamin
      D levels. Therefore, it is understandable that providing tuberculosis patients
      with sunlight may have boosted their immune system and aided them in the fight
      against tuberculosis. In view of the high level of resistance to all drug
      regimens in some patients, perhaps it is time to revive the use of sanatoria in
      the fight against tuberculosis.

PMID- 29465108
TI  - Medicine and the McNamara fallacy.
AB  - The 'McNamara fallacy' (also known as quantitative fallacy) is named after the US
      Secretary of Defense during the Vietnam War. The fallacy consists of over
      reliance on metrics, and may be summarised as: 'if it cannot be measured, it is
      not important'. This paper describes the McNamara fallacy as it applies to
      medicine and healthcare, taking as examples hospital mortality data, NHS targets
      and quality assurance.

PMID- 29465109
TI  - In Carthage ruins: the illness of Sir Winston Churchill at Carthage, December
      1943.
AB  - This paper reviews Churchill's illness in Carthage in December 1943. It was
      characterised by fever that lasted 6 days, left lower lobe pneumonia and two
      episodes of atrial fibrillation. He was managed in a private villa by Lord Moran,
      his personal physician, with the assistance of two nurses and the expert advice
      of colleagues. Sulphadiazine and digitalis leaf were prescribed and Churchill
      recovered. It is remarkable that, despite the severity of his illness, he
      continued to direct the affairs of State from his bed.

PMID- 29465110
TI  - James Craufurd Gregory, 19th century Scottish physicians, and the link between
      occupation as a coal miner and lung disease.
AB  - By the mid-19th century about 200,000 miners were employed in a UK coal mining
      industry still growing with the advances of the Industrial Revolution. Coal
      miners were long known to suffer poor health but the link to inhaling dust in the
      mines had not been made. In 1813 George Pearson was the first to suggest that
      darkening of lungs seen in normal individuals as they aged was caused by inhaled
      soot from burning oil, candles and coal, which were the common domestic sources
      of heat and light. In 1831 Dr James Craufurd Gregory first described black
      pigmentation and disease in the lungs of a deceased coal miner and linked this to
      pulmonary accumulation of coal mine dust. Gregory hypothesised that the black
      material seen at autopsy in the collier's lungs was inhaled coal dust and this
      was confirmed by chemical analysis carried out by Professor Sir Robert
      Christison. Gregory suggested that coal dust was the cause of the disease and
      warned physicians in mining areas to be vigilant for the disease. This first
      description of what came to be known as 'coal worker's pneumoconiosis' sparked a
      remarkable intellectual effort by physicians in Scotland, culminating in a large
      body of published work that led to the first understandings of this disease and
      its link to coalblackened lungs. This paper sets out the history of the role of
      Scottish physicians in gaining this understanding of coal worker's
      pneumoconiosis. It describes Gregory's case and the lung - recently discovered in
      the pathology collection of the Surgeons' Hall Museums, Edinburgh, where it has
      lain unnoticed for over 180 years - on which Gregory based his landmark paper.

PMID- 29465111
TI  - CRP and ESR in giant cell arteritis.

PMID- 29465112
TI  - Water transport through graphene oxide membranes: the roles of driving forces.
AB  - Graphene oxide (GO) membranes have shown excellent selectivities in
      nanofiltration and pervaporation. However, the water transport mechanisms in the
      unique membrane laminar structure are still not well understood, especially in
      pervaporation which involves selective permeation and evaporation. Herein, water
      transport in GO membranes was tested under two different modes: pressure-driven
      permeation and pervaporation. The pure water flux was found to be 1-2 orders of
      magnitude higher in pervaporation due to the large capillary pressure induced by
      evaporation. The water flux in pervaporation was suggested to be limited by
      evaporation at room temperature but surface diffusion at high temperature.

PMID- 29465113
TI  - Quantum corral effects on competing orders and electronic states in chiral d + id
      or f-wave superconductors.
AB  - Self-consistent calculations are performed to characterize the quantum corral
      effects on the electronic states of chiral d + id or f-wave superconductors in
      this paper. A variety of spatial structures of competing orders are revealed in
      the presence of ferromagnetic nano-corrals, and superconducting islands are found
      to be absent in the case of small corrals while being seen for large corrals.
      Compared with the local suppression of superconductivity by a magnetic impurity
      inside the corral, surprisingly, an additional remarkable feature, i.e., obvious
      oscillations or enhancement of superconductivity around a non-magnetic impurity,
      is observed inside the magnetic corral. This is important in view of
      applications, especially in view of the demand for devices to locally produce
      strong superconductivity. Meanwhile, the charge density displays obvious
      modulations due to quantum confinement but in contrast, the spin density pattern
      exhibits its robustness against the corral effect. Furthermore, we explore the
      local density of states so as to be directly checked by experiments. We
      demonstrate that a magnetic corral can suppress the formation of quasi-particle
      bound states induced by an impurity inside the corral in the chiral d + id state
      while the f-wave case shows different behaviors. These results also propose a new
      route to make a distinction between the two competing pairing states in
      triangular-lattice superconductors.

PMID- 29465114
TI  - Water transport confined in graphene oxide channels through the rarefied effect.
AB  - Understanding the mechanism of water transport inside an interlayer between
      graphene-based plates has tremendous value for theoretical studies and industrial
      applications. The fluid flow confined in nano-scaled spaces experiences a slip
      velocity near the wall, which is significantly different to that of bulk water.
      Here we propose a model combining classic hydrodynamics with kinetic theory to
      depict the dependency of the slip effect on the oxide concentration of valley
      plates. The influence of oxidized graphene on water flow is a comprehensive
      result of a slipped boundary, and depends on both the diffuse reflection
      coefficient of the wall, and the shrunken effective passageway caused by the
      electrostatic interactions between the oxidized surface and the water molecules.
      The former effect enhances the water flow, which reduces with increasing oxide
      concentration, while the latter effect inhibits water flow. We examine the
      diffuse reflection coefficient and the shrunken effective passageway at different
      oxide concentrations of the GO sheets by molecular dynamics simulations, and we
      quantitively predict the flux relationship at various concentrations. This work
      provides a molecular insight into transport processes of confined water and a
      useful guideline for the design of perfect graphene-derived membranes for
      desalination.

PMID- 29465115
TI  - Enhanced photocatalytic properties of ZnO nanorods by electrostatic self-assembly
      with reduced graphene oxide.
AB  - A series of ZnO nanorod (NR)-reduced graphene oxide (rGO) nanocomposites (NCs)
      (i.e., ZnO-rGO NCs) with varying rGO loadings were fabricated by electrostatic
      self-assembly of positively charged ZnO NRs with negatively charged graphene
      oxide (GO), followed by the hydrothermal reduction of GO to rGO. When compared
      with bare ZnO NRs, ZnO-5% rGO exhibited significant photoactivity 6 times higher
      in the photodegradation of rhodamine B (RhB), and 2 times higher than ZnO-5%
      rGO(H) synthesized by hard integration of GO and ZnO NRs. In the same manner, ZnO
      5% rGO exhibited a significant photoactivity 3 times higher in photodegrading
      phenol, which is 2 times higher than ZnO-5% rGO(H). Furthermore, the adsorption
      properties of ZnO-rGO NCs towards RhB and phenol were significantly different as
      a result of the opposite charges of the two pollutants in aqueous solution, which
      also led to the formation of different key free radicals during the degradation
      reaction. Based on various characterization techniques, it is concluded that the
      enhanced photoactivity and photostability of ZnO-5% rGO originated from the
      synergistic effects between ZnO NRs and rGO nanosheets including higher specific
      surface area, enhanced photogenerated carrier separation, and strengthened
      protection effects from intimate rGO coupling. However, these synergistic effects
      were weaker in ZnO-5% rGO(H) which reflects the key importance of surface charge
      modification in producing a well-contacted interface.

PMID- 29465116
TI  - Polyphenols-rich extract from Pleurotus eryngii with growth inhibitory of HCT116
      colon cancer cells and anti-inflammatory function in RAW264.7 cells.
AB  - Edible mushrooms are rich sources of bioactive components. In this study, a
      polyphenol-rich extract, designated as PPEP, was isolated from an edible
      mushroom, Pleurotus eryngii. Using ultra high performance liquid chromatograph
      combined with triple time-of-flight mass spectrometry (UPLC-TOF/MS/MS), gallic
      acid monohydrate, 3-(3,4-dihydroxyphenyl)-propionic acid, methyl gallate,
      syringic acid, ellagic acid and catechin were identified in PPEP. This phenolic
      rich extract PPEP exhibited anti-inflammatory effect in lipopolysaccharide
      stimulated RAW264.7 macrophages by inhibiting the overproduction of pro
      inflammatory mediators including nitric oxide (NO) and reactive oxygen species
      (ROS). It was demonstrated that the anti-inflammatory effects of PPEP were
      associated with the inhibition of iNOS expression, suppression of p-IkappaB
      protein expression and inhibition of NF-kappaB and IkappaB mRNA expression. Next,
      the inhibitory effect of PPEP against human colon cancer cells was also
      determined. PPEP suppressed cell proliferation of human colon cancer HCT116 cells
      in a dose- and time-dependent fashion, while it showed no inhibitory effect on
      normal human colonic myofibroblasts CCD-18Co cells at the same tested
      concentrations (0-200 MUg mL-1). Moreover, PPEP induced cell cycle arrest and led
      to extensive cellular apoptosis in human colon cancer cells, which was associated
      with the downregulation of cell cycle-related signaling protein, e.g. cyclin B
      and cyclin E, and the upregulation of apoptosis-related signaling protein caspase
      3 and cleaved caspase-3. Overall, our results provided a basis for using PPEP as
      a promising preventive agent against inflammatory disease and colon cancer.

PMID- 29465117
TI  - Gold(i) phosphine compounds as parasite attenuating agents for malaria vaccine
      and drug development.
AB  - Here, the anti-malarial activity of two gold(i) phosphine compounds auranofin and
      [Au(d2pype)2]Cl (where d2pype is 1,2-bis(di-2-pyridylphosphino)ethane), were
      examined to inform their use as potential drugs and malaria parasite-attenuating
      agents. In vitro, the gold compounds were active against Plasmodium falciparum
      and P. knowlesi as well as the rodent parasite P. chabaudi AS. Attenuation of the
      parasite was observed when mice were inoculated with P. chabaudi AS infected red
      blood cells treated in vitro with [Au(d2pype)2]Cl (1 or 2 MUM) or auranofin (2
      MUM) for 2 or 3 h. Quantitative PCR data showed persistence of low levels of
      parasite DNA up to 8 days post inoculation. In some experiments, there was
      microscopically detectable parastiemia following inoculation which subsequently
      cleared. Following 1 or 3 doses of gold compound-treated parasitized red blood
      cells (pRBCs), protection was not observed when these mice were subsequently
      challenged with wild type P. chabaudi AS. In experiments where microscopically
      detectable parasites were observed following in vivo inoculation, mice were
      subsequently fully protected against a challenge infection with wildtype
      parasites. In an infect-and-treat rodent model, the gold compounds were unable to
      inhibit P. chabaudi AS growth in vivo when administered orally. Gold compounds
      act via the inhibition of antioxidant systems which are critical in the
      pathogen's survival from attack by the host oxidants. In vitro, they directly
      inhibit the parasite thioredoxin reductase, hence the observed suppressive
      activity. On the other hand, in vivo, the gold compounds may not be readily
      available for absorption and thus pharmacokinetic studies will be required to
      further examine drug bioavailability following administration. With structural
      differences in redox mechanisms of P. falciparum and the human host being
      identified, gold compounds can be better designed to more efficiently target and
      selectively inhibit the parasite.

PMID- 29465118
TI  - Electric field analyses on monolayer semiconductors: the example of InSe.
AB  - External electric fields can be used to manipulate the electronic properties of
      two-dimensional (2D) materials. 2D InSe semiconductors possess high electron
      mobility and wide band gap tunability. Therefore, they have been proposed for use
      in ultrathin electronic devices. Here, using first-principles calculations, we
      study the charge polarization, structure, electronic structure, and gas
      adsorption of an InSe monolayer under vertical electric fields. We find that both
      the structural evolution and charge polarization rely on the directions of the
      electric fields. The hole effective mass at the valance band maximum can be
      decreased by fields that offer a possible route to increase mobility. In
      contrast, the fields have little impact on the effective mass of electrons at the
      conduction band minimum. Therefore, high electron mobility in InSe is retained
      under the fields. Besides, electric fields could alter the absorption intensity
      for gas molecules. Therefore, gas sensors could be an expected application. More
      importantly, this work systematically points out some key steps for setting up
      electric-field calculations in the popular VASP code, such as the cancellation of
      the symmetrisation of the charge density, avoiding electrons spilling out into
      the vacuum under high fields.

PMID- 29465119
TI  - Chemical synthesis of culmorin metabolites and their biologic role in culmorin
      and acetyl-culmorin treated wheat cells.
AB  - The Fusarium metabolite culmorin (1) is receiving increased attention as an
      "emerging mycotoxin". It co-occurs with trichothecene mycotoxins and potentially
      influences their toxicity. Its ecological role and fate in plants is unknown. We
      synthesized sulfated and glucosylated culmorin conjugates as potential
      metabolites, which are expected to be formed in planta, and used them as
      reference compounds. An efficient procedure for the synthesis of culmorin
      sulfates was developed. Diastereo- and regioselective glucosylation of culmorin
      (1) was achieved by exploiting or preventing unexpected acyl transfer when using
      different glucosyl donors. The treatment of a wheat suspension culture with
      culmorin (1) revealed an in planta conversion of culmorin into culmorin-8
      glucoside (6) and culmorin acetate, but no sulfates or culmorin-11-glucoside (7)
      was found. The treatment of wheat cells with the fungal metabolite 11
      acetylculmorin (2) revealed its rapid deacetylation, but also showed the
      formation of 11-acetylculmorin-8-glucoside (8). These results show that plants
      are capable of extensively metabolizing culmorin.

PMID- 29465120
TI  - High-performance optical projection controllable ZnO nanorod arrays for
      microweighing sensors.
AB  - Optical microweighing sensors are an essential component of micro-force
      measurements in physical, chemical, and biological detection fields, although,
      their limited detection range (less than 15 degrees ) severely hinders their wide
      application. Such a limitation is mainly attributed to the essential restrictions
      of traditional light reflection and optical waveguide modes. Here, we report a
      high-performance optical microweighing sensor based on the synergistic effects of
      both a new optical projection mode and a ZnO nanorod array sensor. Ascribed to
      the unique configuration design of this sensing method, this optical
      microweighing sensor has a wide detection range (more than 80 degrees ) and a
      high sensitivity of 90 nA deg-1, which is much larger than that of conventional
      microcantilever-based optical microweighing sensors. Furthermore, the location of
      the UV light source can be adjusted within a few millimeters, meaning that the
      microweighing sensor does not need repetitive optical calibration. More
      importantly, for low height and small incident angles of the UV light source, we
      can obtain highly sensitive microweighing properties on account of the highly
      sensitive ZnO nanorod array-based UV sensor. Therefore, this kind of large
      detection range, non-contact, and non-destructive microweighing sensor has
      potential applications in air quality monitoring and chemical and biological
      detection.

PMID- 29465125
TI  - Mismatch in cation size causes rapid anion dynamics in solid electrolytes: the
      role of the Arrhenius pre-factor.
AB  - Crystalline ion conductors exhibiting fast ion dynamics are of utmost importance
      for the development of, e.g., sensors or rechargeable batteries. In some layer
      structured or nanostructured compounds fluorine ions participate in remarkably
      fast self-diffusion processes. As has been shown earlier, F ion dynamics in
      nanocrystalline, defect-rich BaF2 is much higher than that in the coarse-grained
      counterpart BaF2. The thermally metastable fluoride (Ba,Ca)F2, which can be
      prepared by joint high-energy ball milling of the binary fluorides, exhibits even
      better ion transport properties. While long-range ion dynamics has been studied
      recently, less information is known about local ion hopping processes to which
      19F nuclear magnetic resonance (NMR) spin-lattice relaxation is sensitive. The
      present paper aims at understanding ion dynamics in metastable, nanocrystalline
      (Ba,Ca)F2 by correlating short-range ion hopping with long-range transport
      properties. Variable-temperature NMR line shapes clearly indicate fast and slow F
      spin reservoirs. Surprisingly, from an atomic-scale point of view increased ion
      dynamics at intermediate values of composition is reflected by increased absolute
      spin-lattice relaxation rates rather than by a distinct minimum in activation
      energy. Hence, the pre-factor of the underlying Arrhenius relation, which is
      determined by the number of mobile spins, the attempt frequency and entropy
      effects, is identified as the parameter that directly enhances short-range ion
      dynamics in metastable (Ba,Ca)F2. Concerted ion migration could also play an
      important role to explain the anomalies seen in NMR spin-lattice relaxation.

PMID- 29465126
TI  - Effects of a galacto-oligosaccharide-rich diet on fecal microbiota and metabolite
      profiles in mice.
AB  - Galacto-oligosaccharides (GOS) are prebiotics that positively affect the host's
      gut microbiota, which is important for the health of the host. Most previous
      studies focused on specific flora components (e.g. Bifidobacterium and
      Lactobacillus); very few have investigated the relationship between flora and
      metabolites. Here, we used 16S rRNA analysis and metabolomics to analyze the
      effect of GOS on microbiota and metabolites. Results show that the abundance of
      Ruminococcaceae and Oscillibacter decreased significantly in GOS-fed mice. Twenty
      one metabolites, including oleic acid, arachidic acid, and behenic acid,
      decreased significantly in the GOS-fed mice. Fatty acid synthesis and blood
      triglyceride content significantly decreased in the GOS-fed mice compared with
      those in the control mice, suggesting that GOS may improve lipid metabolism in
      mice. Additionally, after three weeks of a GOS-rich diet, the mouse microbiota
      was significantly enriched in Alloprevotella, Bacteroides, and Parasutterella.
      The blood glucose level of the GOS-fed group was significantly higher than that
      of the control group, whereas the abundance of Coprococcus and Odoribacter
      (butyrate-producing bacteria) was significantly decreased. The metabolism of
      butyrate, known to reduce plasma glucose levels, was significantly downregulated
      in the GOS-fed mice, an effect potentially detrimental to the glucose metabolism
      of the host. This dual-omics analysis provided important information on the
      changes in host-microbe-metabolite interactions resulting from GOS
      supplementation. Our results provide evidence that GOS may improve lipid
      metabolism, and that long-term GOS supplementation had a detrimental effect on
      the host's glucose metabolism, which could be important for optimizing methods of
      prebiotic supplementation and developing approaches to prevent diseases using
      prebiotic interventions.

PMID- 29465128
TI  - Catalytic synthesis of boron nitride nanotubes at low temperatures.
AB  - KFeO2 is demonstrated to be an efficient catalyst for the formation of boron
      nitride nanotubes (BNNT) by thermal chemical vapor deposition (TCVD). This alkali
      based catalyst enables the formation of crystalline, multi-walled BNNTs with high
      aspect ratio at temperatures as low as 750  degrees C, significantly lower than
      those typically required for the product formation by TCVD.

PMID- 29465129
TI  - The photolysis of alpha-hydroperoxycarbonyls.
AB  - In this work, we theoretically elucidated the mechanism and predicted the major
      products of the photolysis of alpha-hydroperoxycarbonyls, known to be products of
      the atmospheric oxidation of biogenic volatile organic compounds (BVOC) and
      components of secondary organic aerosol (SOA) in rural and remote areas. Using 2
      hydroperoxypropanal OCHCH(OOH)CH3 as a model compound, we show that the likely
      major photolysis mechanism is a fast 1,5 H-shift in the initially excited singlet
      S1 state followed by spontaneous elimination of singlet oxygen to yield an enol
      HOCH[double bond, length as m-dash]CHCH3, while intersystem crossing (ISC) to the
      triplet T1 state and C-C scission into HCO + HOOCHCH3 followed by expulsion of a
      hydroxyl radical from the unstable HOOCHCH3 is another product channel. The
      direct S1 reaction was found to occur at such a high rate that the quantum yield
      in atmospheric conditions is expected to approach unity. In the atmosphere, the
      enol should generally react with OH radicals or tautomerize into the more stable
      carbonyl O[double bond, length as m-dash]CH-CH2CH3. Vinylalcohol is shown to be a
      major end product of the photolysis of hydroperoxyacetaldehyde, an isoprene
      oxidation product. Taking into account also the important enhancement of the
      absorption cross sections over those of the constituent monofunctional compounds
      as observed for the analogous beta-ketohydroperoxides, (F. Jorand et al., J.
      Photochem. Photobiol. A: Chem., 2000, 134, 119-125) the atmospheric photolysis
      rate of alpha-hydroperoxycarbonyls was estimated to be in the range of (1 to 5) *
      10-4 s-1, generally faster than the rate of their OH reactions.

PMID- 29465130
TI  - Targeted VEGF-triggered release of an anti-cancer drug from aptamer
      functionalized metal-organic framework nanoparticles.
AB  - Amino-triphenyl dicarboxylate-bridged Zr4+ metal-organic framework nanoparticles
      (NMOFs), 100-130 nm, are modified with a nucleic acid complementary to the VEGF
      aptamer. The nucleic acid-functionalized NMOFs were loaded with the anti-cancer
      drug doxorubicin (or Rhodamine 6G as a drug model), and the loaded NMOFs were
      capped by hybridization with the VEGF aptamer that yielded VEGF-responsive duplex
      nucleic acid gates. In the presence of VEGF, a biomarker over-expressed in cancer
      cells, selective unlocking of the gates proceeds through the formation of
      VEGF/aptamer complexes, resulting in the release of the loads. In addition, the
      VEGF aptamer locking units were conjugated to the AS1411 aptamer sequence that
      binds to nucleolin receptors associated with cancer cells, resulting in the
      construction of cancer-cell targeted VEGF-responsive doxorubicin-loaded NMOFs.
      The different drug-loaded stimuli-responsive NMOFs reveal selective permeation
      into MDA-MB-231 breast cancer cells, compared to their incorporation into normal
      MCF-10A breast cells, with a two-fold enhanced incorporation into the MDA-MB-231
      cells of the AS1411 aptamer-functionalized NMOFs. Cytotoxicity experiments
      revealed impressive selective apoptosis of the doxorubicin-loaded NMOFs towards
      the MDA-MB-231 cancer cells compared to the normal MCF-10A breast cells. A 55%
      and 70% MDA-MB-231 cell apoptosis was observed upon subjecting the cells to the
      VEGF aptamer and the VEGF aptamer/AS1411 aptamer conjugate-caged NMOFs,
      respectively, for a time-interval of three days, where only <10% apoptosis of the
      MCF-10A cells was observed under similar conditions.

PMID- 29465131
TI  - Hierarchically ZnIn2S4 nanosheet-constructed microwire arrays: template-free
      synthesis and excellent photocatalytic performances.
AB  - Hierarchically ZnIn2S4 nanosheet-constructed microwire arrays (NCMAs) on a zinc
      substrate have been synthesized for the first time through a one-step
      solvothermal method without using any template or surfactant. The as-synthesized
      ZnIn2S4 microwires are constructed by vertical nanosheets preferentially exposing
      (006) facets, which are about 1-5 MUm in diameters and larger than 10 MUm in
      average length. Experimental results demonstrate that the hierarchically ZnIn2S4
      NCMAs are converted from intermediate components of single crystalline indium
      nanowires, which are generated along the direction of (101) planes by a
      displacement reaction between Zn and In3+ during the initial synthesis process.
      This conversion of indium nanowires to hierarchically ZnIn2S4 NCMAs has been
      explained by a novel corrosion-exchange-self-assembly mechanism, which might
      indicate a novel strategy for preparing other ternary sulphide nano-microwire
      arrays. The prepared ZnIn2S4 NCMAs are used as photocatalysts, demonstrating
      effective photocatalytic degradation activity for diverse organic pollutants
      including different dyes, tetracycline and 2,4,6-tribromophenol (2,4,6-TBP). This
      efficient photocatalytic activity is ascribed to the strong absorption of ZnIn2S4
      NCMAs in a wide range from ultraviolet to visible light as well as the
      preferentially exposed (006) facets of ZnIn2S4 nanosheets.

PMID- 29465145
TI  - Immunisation Registries at regional level in Italy and the roadmap for a future
      Italian National Registry.
AB  - BACKGROUND: Immunization Information Systems, or Immunisation registries (IRs),
      are essential to monitor and evaluate the accessibility, quality and outcomes of
      immunisation programmes both at local and national level. STUDY DESIGN: We
      conducted a cross-sectional survey in order to investigate and map the level of
      IRs implementation obtained by the 21 Italian Regional Health Authorities. On
      this basis we defined a roadmap towards implementing an Italian National IR.
      METHODS: We designed an online questionnaire. Data were collected from July to
      September 2016 from all the 21 Regional Health Authorities in charge of
      infectious diseases control and immunization management. RESULTS: 18/21 Italian
      Regions have fully implemented an IR, out of them, 11 use the same software for
      all Local Health Units. Two Regions have partially implemented their IRs and one
      Region is not yet computerised. CONCLUSION: The decentralization of the Italian
      Health System is reflected also on the IRs characteristics and functionalities in
      terms of fragmented implementation of IRs and diversity in the software systems
      and data flows in place. Future efforts should not only aim not only to clarify
      the functionalities of Regional IRs, but should also aim to define how
      aggregation of data at national level can be optimised.

PMID- 29465146
TI  - Vaccine hesitancy, a public health problem.
AB  - The phenomenon of "vaccine hesitancy" has only been studied for a few years, and
      this attitude is becoming a serious threat that can frustrate the efforts of
      recent years that have led to the achievement of relevant scientific advances to
      human health. The paper analyzes the possible causes, the scope of the phenomenon
      and its consequences, trying to identify the most effective actions to resolve
      this trend.

PMID- 29465147
TI  - Research on mesophilic aerobic microorganisms and Enterobacteriaceae in
      cultivated and commercialized Agaricus bisporus.
AB  - BACKGROUND: Production and consumption of fresh mushrooms reached high levels in
      recent years but only a few data regarding microbiological quality of these
      products are available, although their potential microbial load is expected to be
      high. EU and Italian legislation have not set a limit on microbial counts in
      these products and label information is often unclear. This study investigates
      the microbial quality of samples of fresh cultivated mushrooms sold in Tuscany so
      that both food business operators and legislators can obtain data about potential
      microbial risk for consumers and debate about the opportunity of realizing an
      update on fresh mushrooms labels that should include information to protect
      consumers' health. STUDY DESIGN: This study reports the microbial load in samples
      of cultivated and commercialized Agaricus bisporus. Samples were obtained from
      different shops in Florence, chosen among those products whose labels did not
      indicate how the product should be consumed. METHODS: From March through May
      2014, 20 couples of samples of A. bisporus were acquired in Florence.
      Microbiological analysis included the quantification of the microbial counts for
      mesophilic aerobic microorganisms and Enterobacteriaceae, as indicators of
      hygienic practices during cultivation and manufacturing. The analyses were
      carried out at two subsequent stages: one immediately (T0) and one at the end of
      the shelf life (T1), i.e. close to the expiry date stated on the label. RESULTS:
      The high microbial load observed exceeds the reference values set as acceptable
      for raw foods in Tuscany and is worse than the ones reported in other studies on
      this subject. The results are particularly alarming in light of the fact that A.
      bisporus is usually consumed raw and there is no mandatory specification on the
      label that informs consumers that the product must be cooked before being
      consumed. CONCLUSION: This research highlights the importance of adequate and
      complete information on fresh mushrooms labels, that should include information
      about the need for sanitization before the consumption, the appropriate storage
      temperature, and the maximum duration of shelf life. Data obtained could also be
      useful for food business operators to gather information about the microbial
      quality of fresh cultivated commercialized mushrooms in order to implement
      quality controls of the production process and storage conditions.

PMID- 29465148
TI  - Antibiotic resistance and frequency of class 1 integrons among Pseudomonas
      aeruginosa isolates obtained from wastewaters of a burn center in Northern Iran.
AB  - BACKGROUND: Pseudomonas aeruginosa, being responsible of a broad variety of
      infections, is considered an important nosocomial pathogen. The emergence of
      multiple-drug resistance among strains of P. aeruginosa appeared as a further
      public health concern. Due to the considerable ability of multiple-drug resistant
      P. aeruginosa strains to transmit themselves in the environment, we aimed to
      investigate the association of class 1 integrons with the antibiotic resistance
      profile of P. aeruginosa strains isolated from hospital wastewaters. METHODS: In
      this cross-sectional study, a total of 100 P. aeruginosa isolates were obtained
      from raw wastewater samples from February 2010 to January 2011 in a Teaching Burn
      Hospital in Guilan province. All isolates were identified as P. aeruginosa using
      standard microbiological tests. Antibiotic susceptibility was investigated using
      the disk diffusion method according to Clinical and Laboratory Standards
      Institute recommendations. All isolates were assayed for the presence of the
      class 1 integrons gene by PCR. RESULTS: Overall, 30 (30%) P. aeruginosa isolates
      were positive for the presence of class 1 integrons. The highest antibiotic
      resistance rates in both integron-positive and -negative isolates belonged to
      cephalexin and cephazolin, with 100% resistance. Amikacin and ciprofloxacin with
      the lowest level of resistance (13.3%) were the effective antibiotics against
      integron-positive isolates. The rates of MDR isolates were significantly higher
      among integron-positive isolates with 43.3% compared to negative isolates with
      22.9% (P < 0.05). CONCLUSION: The results highlight the importance of class 1
      integrons in multiple antibiotic resistance among P. aeruginosa isolates.
      Moreover, the spread of hospital derived wastewaters in the environment can be
      regarded as the origin of significant reservoirs for antibiotic-resistant
      pathogens.

PMID- 29465149
TI  - Can a program of food and diabetes education improve the quality of the lives of
      diabetic patients with a previous myocardial infarction?
AB  - BACKGROUND AND OBJECTIVES: People with diabetes and cardiovascular complications
      need to be educated about the self-management of the disease at the time of
      diagnosis and during the follow-up to best benefit from what they learn.
      Education is most effective when offered to small groups of patients led by a
      professional team. The aim of the study is the evaluation of diabetes and food
      education aimed at improving the self-awareness of the disease, the management
      and the quality of the lives of diabetic patients with a previous myocardial
      infarction. METHODS AND RESULTS: The sample group consisted of 20 subjects
      suffering from diabetes mellitus type 2 with a previous myocardial infarction.
      First, subjects were administered a test to assess the degree of knowledge of
      diabetes and quality of life; they also performed a walking test and a food
      interview. Anthropometric assessments and serum chemistry parameters were taken
      into consideration. Subsequently, they attended 7 lessons on nutrition, diabetes
      and cardiovascular complications; post intervention, the sample group
      demonstrated statistically significant improvement in the knowledge of the
      disease, in anthropometric measurements and walking test. CONCLUSION: Although we
      have not found an improvement of biochemical parameters, informing diabetic
      subjects of their health conditions and complications is essential in order to
      achieve patient empowerment and the compliance.

PMID- 29465150
TI  - Frailty screening and assessment tools: a review of characteristics and use in
      Public Health.
AB  - INTRODUCTION: Frailty screening and assessment are a fundamental issue in Public
      Health in order to plan prevention programs and services. METHODOLOGY: By a
      narrative review of the literature employing the International Narrative
      Systematic Assessment tool, the authors aims to develop an updated framework for
      the main procedures and measurement tools to assess frailty in older adults,
      paying attention to the use in the primary care setting. RESULTS: The study
      selected 10 reviews published between January 2010 and December 2016 that define
      some characteristics of the main tools used to measure the frailty. Within the
      selected reviews only one of the described tools met all the criteria
      (multidimensionality, quick and easy administration, accurate risk prediction of
      negative outcomes and high sensitivity and specificity) necessary for a screening
      tool. CONCLUSION: Accurate risk prediction of negative outcomes could be the
      appropriate and sufficient criteria to assess a tool aimed to detect frailty in
      the community-dwelling elderly population. A two-step process (a first short
      questionnaire to detect frailty and a second longer questionnaire to define the
      care demand at individual level) could represent the appropriate pathway for
      planning care services at community level.

PMID- 29465151
TI  - Pre-pregnancy body mass index, gestational weight gain and adverse birth
      outcomes: some evidence from Italy.
AB  - BACKGROUND: Overweight and obese women present an increased risk of poor maternal
      and child health outcomes. The aim of this paper is to analyze the joint effects
      of pre-pregnancy body mass index and inadequate gestational weight gain on birth
      weight and gestational age in an Italian sample of pregnant women. METHODS: Data
      were obtained from a sample of about 2,000 pregnant women at the University
      Teaching Hospital of Perugia University (Italy) in 2013. We used the revised
      classification proposed by Institute of Medicine to identify gestational weight
      gains considered as appropriate. Logistic regression models were used to estimate
      the adjusted odds-ratios of women belonging to any BMI class different from
      normal (used as the reference category) and of women who increased their weight
      by an amount smaller or greater than normal, controlling for a large set of
      observable confounders. RESULTS: Higher probability of low birth weight was
      associated with both obesity (OR = 1.9124, s.e. = 0.526) and less than normal
      weight gains (OR = 2.3614, s.e. = 0.388). The probability of fetal macrosomia was
      found to be positively associated with more than normal weight increases (OR =
      2.6232, s.e. = 0.465). Pre-term deliveries were associated with less than normal
      gestational weight gains (OR 1.7338, s.e. = 0.320). CONCLUSION: Overweight and
      obesity represent a big issue for public health. In particular, weight management
      during pregnancy and pre-pregnancy could determine negative health outcomes in
      newborns. In our study we found that inadequate weight variations during
      pregnancy, according to the Classification of the Institute of Medicine,
      negatively influence health conditions at birth. Stronger initiatives, especially
      in terms of midwifery, nurse training and informative policies should be adopted
      by policy makers.

PMID- 29465152
TI  - Inter- and intra-interviewer reliability of Italian version of Pediatric
      Evaluation of Disability Inventory (I-PEDI).
AB  - BACKGROUND: Childhood disabilities determine a range of immediate and long-term
      economic costs that have important implications for the well-being of the child,
      the family and the society. The Pediatric Evaluation of Disability Inventory
      (PEDI) measures capability and performance in children aged between 6 months and
      7.5 years. It contains three scales: Functional Skills Scales (FSS), Caregiver
      Assistance Scale (CAS) and Modifications Scale (MS). The present study evaluated
      the measurement properties of the Italian version of the PEDI (PEDI-I) in
      patients with spastic cerebral palsy (CP). STUDY DESIGN: Reliability study.
      METHODS: The original PEDI was translated - including a cross-cultural adaptation
      - into Italian. Internal consistency and test-retest reliability were evaluated.
      RESULTS: Fifty-eight children with CP were recruited. According to inter
      interviewer reproducibility, the FSS domain revealed intraclass correlation
      coefficient (ICC) values ranging between 0.94 and 1.00. CAS domain revealed ICC
      values ranging between 0.94 and 1.00. The SEM values ranged between 3.25
      (SDD=8.98) for SF and 5.24 for SC (SDD=14.5). According to intra-interviewer
      reproducibility, the FSS domain revealed ICC values ranging between 0.99 and
      1.00. CAS domain revealed ICC values ranging between 0.92 and 0.99. The SEM
      values ranged between 3.44 (SDD=9.5) for SF and 3.75 for SC (SDD=10.36). The
      inter-interviewer and intra-interviewer reproducibility results showed very high
      ICC values for both FFS and CAS domains. Cronbach's alpha ranged between 0.94 and
      0.99, indicating excellent internal consistency within each domain of the PEDI-I.
      CONCLUSION: The inter-interviewer and intra-interviewer reproducibility results
      of PEDI-I showed very high ICC values for FFS and CAS domains. Therefore, we
      recommend its application to evaluate the effect of treatment in children with
      CP.

PMID- 29465153
TI  - Knowledge and Attitudes on Food Hygiene among Food Services Staff on Board Ships.
AB  - BACKGROUND: Ships have long been sites for outbreaks of infectious diseases,
      particularly gastrointestinal diseases. The ship environment has the potential to
      facilitate the spread of such diseases, infecting susceptible cohorts of embarked
      passengers and crew. Gastrointestinal disorders among seafarers are fairly common
      and usually represent the first or second cause of requests for medical
      assistance aboard ships in international waters. STUDY DESIGN: The purpose of
      this study was to evaluate food safety and the level of knowledge among food
      service personnel on board merchant ships, where food handlers could be a cause
      of health problems for all crew members. METHODS: An anonymous self-administered
      questionnaire containing specific questions about food hygiene and safety
      knowledge was administered. RESULTS: The overall score of correct answers for the
      food safety aspects tested was 51.77 (SD 3.87) out of 76 points, corresponding to
      68.12% of questions answered correctly. Food workers who followed a training
      course showed higher mean knowledge score (p < 0.05) compared to not-trained
      workers. The most relevant significant differences (p < 0.05) were noticeable in
      the personal hygiene, cross-contamination, safe storage, and knowledge of
      foodborne pathogens sections. CONCLUSION: Food services staff on board cargo
      ships should be adequately trained and should understand basic and fundamental
      aspects of food hygiene, related pathologies and sanitation, as they are
      responsible for the health and wellbeing of many seafarers.

PMID- 29465154
TI  - Implications of modified food choices and food-related lifestyles following the
      economic crisis in the Marche Region of Italy.
AB  - BACKGROUND: The economic crisis in Italy has led to profound changes in resource
      management not only at the macro level but also for individual families, causing
      substantial changes in different habits of Italians. STUDY DESIGN: The purpose of
      this research was to conduct a study on changes in family eating habits
      potentially triggered by the economic crisis was conducted in an area of the
      Marche Region in central Italy. METHODS: The research was conducted in the period
      2016 - 2017 by administering a specific and anonymous questionnaire. RESULTS: The
      interviewed people has reduced its food consumption. In particular, analyzing the
      results for the animal protein food group, there has been a reduction in purchase
      of beef, and an increase in that of pork. Overall fish consumption has decreased
      by 44%, with a decrease in the purchase of fresh fish, and an increase in that of
      canned fish products. Finally, consumers have reduced their purchases of fresh
      and canned legumes, fresh vegetables, and fresh fruit. CONCLUSION: The economic
      crisis seems to have changed the eating habits and food-related lifestyle choices
      of the subjects studied, especially in the urban area affected by the deeper
      economic depression. These changes are likely to have permanent social
      consequences, and deserve to be analyzed also in smaller territories in order to
      better understand the dynamics of individual choices and the social framework.

PMID- 29465155
TI  - Effects of physical activity on sclerostin concentrations.
AB  - : Osteoporosis is a serious medical and socioeconomic problem of the 21st
      century. Mechanical load is a key regulator which controls bone formation and
      remodelling, with participation of osteocytes. Sclerostin is produced and
      released by mature osteocytes into bone surface, where it inhibits the conveyance
      of osteoblast proliferation and differentiation activating signals from
      mesenchymal cells, thus suppressing new bone formation. The goal of the study was
      an evaluation of the effects of a 12-week physical training programme on the
      levels of bone turnover markers [Sclerostin, Osteocalcin (OC), C-terminal
      telopeptide of type I collagen (beta-CTX)] in blood serum of women with
      osteopenia. MATERIALS & METHODS: The study included 50 women of the Regional
      Menopause and Osteoporosis Centre of the WAM Teaching Hospital, at the age of 50
      75 years with the diagnosis of osteopenia, obtained on the basis of hip and/or
      lumbar spine densitometry (T-score from -1.0 to -2.5 SD). During the initial 12
      weeks (between point 1 and 2), the patients maintained their previous, normal
      level of physical activity. During subsequent 12 weeks (between point 2 and 3), a
      programme of exercise was implemented. The programme included the interval
      training on a bicycle ergometer, three times a week for 36 minutes. During the
      entire study duration, all the patients received a supplementation of calcium
      (500 mg) and vit. D3 (1800 IU) once daily. Serum levels of OC, alkaline
      phosphatase (ALP), beta-CTX and sclerostin were assayed at 3 time points.
      RESULTS: After the course of the exercise cycle, the OC concentration was
      increased, sclerostin levels decreased, while no statistical differences were
      observed in beta-CTX levels vs. the period of physical inactivity. No
      correlations were found between sclerostin level changes and osteocalcin level
      changes during the training time, because of too small groups. Neither
      statistically significant were the differences in alkaline phosphatase, calcium
      and phosphorus levels. CONCLUSIONS: The obtained results emphasise the role of
      physical training as an effective stimulation method of bone formation processes
      in women with osteopenia. Sclerostin can be a marker of physical activity. < /p >
      < p >.

PMID- 29465156
TI  - The impact of serum adropin and ischemia modified albumin levels based on BMI in
      PCOS.
AB  - INTRODUCTION: The aim of this study was to evaluate the effects of polycystic
      ovary syndrome (PCOS) and body mass index (BMI) on serum adropin and ischemia
      modified albumin (IMA) levels. MATERIALS AND METHODS: This prospective cross
      sectional study was performed with a total of 120 women [group1; non-PCOS = 60
      (BMI < 25 = 30, BMI >=25 = 30) and group 2; PCOS = 60 (BMI < 25 = 30, BMI >=25 =
      30)]. Blood samples were collected between the third and fifth days of the
      women's menstrual cycles after a night of fasting. RESULTS: There were no
      differences between the groups in relation to age, basal follicle stimulating
      hormone, estradiol, thyroid stimulating hormone, prolactin, high-density
      lipoprotein cholesterol, total testosterone, dehydroepiandrosterone sulfate
      levels, systolic and diastolic blood pressures. A significant difference was
      found in basal luteinizing hormone, fasting glucose, insulin, homeostatic model
      assessment of insulin resistance, total cholesterol, low-density lipoprotein
      cholesterol, triglycerides, free testosterone levels, waist-to-hip ratios and the
      Ferriman-Gallwey scores between the PCOS and non-PCOS patients in the lean and
      overweight groups (p < 0.05). The serum adropin levels in the lean PCOS group
      were lower than in the lean non-PCOS group (p < 0.05) and were lower in the
      overweight PCOS group than in the overweight non-PCOS group (p < 0.05). There was
      also a statistically significant difference in serum IMA levels in the PCOS group
      than in the non-PCOS group in both the lean and overweight groups (p < 0.05).
      CONCLUSIONS: Although serum adropin levels were significantly decreased in the
      PCOS group, IMA levels increased. Further studies are needed to determine the
      effects of adropin and IMA in women with PCOS and to use a new marker to
      monitorize treatment outcomes. < /p > < p >.

PMID- 29465157
TI  - Serum concentrations of adipokines in men with prostate cancer and benign
      prostate hyperplasia.
AB  - INTRODUCTION: Obesity and prostate cancer are related, but the causal
      relationship remains unknown. The aim of the study was to compare concentrations
      of leptin, adiponectin and chemerin in patients with prostate cancer and benign
      prostate hyperplasia and to examine associations of the adipokines with the grade
      of prostate cancer, interleukin-6 (IL-6), insulin resistance and anthropometric
      and metabolic variables. MATERIAL AND METHODS: The study group consisted of 140
      men divided into two groups: I- prostate cancer (n=74) and II- with benign
      hyperplasia (n=66). Serum leptin, adiponectin, chemerin, IL-6 and metabolic
      profile were measured. Considering histological differentiation prostate cancer
      patients were divided into 3 subgroups: well differentiated (Gleason score <= 6),
      moderately differentiated subgroup (Gleason 7), and poorly differentiated
      (Gleason >=8). RESULTS: There were no differences between groups in BMI, waist
      circumference, HOMA-I, serum levels of total cholesterol, glucose, triglycerides,
      adiponectin, leptin and chemerin. However, the concentrations of PSA, leptin-to
      adiponectin ratio and IL-6 were significantly higher in cancer group compared
      with benign hyperplasia group. In the poorly differentiated cancer subgroup,
      subjects had higher PSA, leptin, chemerin, IL-6 and triglycerides concentrations.
      Overweight and obese men with prostate cancer were more likely to have moderately
      or poorly differentiated cancer than those with normal BMI. In the all men serum
      adiponectin was significantly correlated with HOMA-I, BMI, glucose,
      triglycerides, cHDL. There were significant correlations between leptin and BMI,
      HOMA-I, waist, glucose, triglycerides and cHDL. Among all the participants we
      observed associations between chemerin and waist as well as triglycerides. In
      prostate cancer patients chemerin correlated with IL-6 and leptin. We measured
      significant positive correlations between Gleason score and chemerin and leptin
      concentrations. There was a positive correlation between adiponectin and PSA
      levels in all men, as well as in cancer group. CONCLUSION: Leptin-to-adiponectin
      ratio and IL-6 were elevated in men with prostate cancer. Leptin, chemerin and IL
      6 were associated with Gleason score. The relationships between leptin, chemerin
      and IL-6 were dependent on each other. Overweight and obese men had a higher
      Gleason score.

PMID- 29465158
TI  - Evaluation of adipokines in children with cystic fibrosis.
AB  - INTRODUCTION: Patients with CF present numerous pathological conditions such as
      malnutrition, depletion of fat-free mass, metabolic disturbances (abnormal
      glucose metabolism, increased insulin resistance, chronic energy deficit, local
      and chronic inflammation), which could affect or be associated with altered
      adipokines concentration Material and Methods: We aimed in this study to
      investigate the levels of selected adipokines such as resistin, apelin,
      adiponectin to demonstrate their application as possible markers of inflammation.
      RESULTS: Serum level of resistin was higher (p < 0.001) and adiponectin - lower
      (p=0.02) in CF children than in healthy children. There was no difference in
      serum apelin level between two examined groups. However, values of
      adiponectin/BMI and apelin/BMI ratios in CF did not differ significantly from
      controls. Higher values of resistin/BMI ratio in CF in comparison to controls
      were observed Serum resistin/adiponectin ratio was significantly higher in CF
      patients than in controls (p < 0.0001). Resistin/BMI ratio correlated negatively
      with FEV1 (R:-48,p < 0.043). Serum resistin/adiponectin ratio correlated
      negatively with FEV1/FVC (R:-49, p=0.04), Adipokines showed no correlation with
      BMI and BMI-SDS, glucose, total cholesterol, and LDL-, HDL-cholesterol,
      triglyceride serum levels. Spirometric parameters FEV1, FVC, VC correlated
      negatively with serum glucose levels (R: -0.55, p < 0.018; R: -0.65 p < 0.0025;
      R:-0.76, p < 0.0008 respectively). FEV1 and FVC correlated positively with BMI
      SDS (R:0.58, p < 0.01; R:0.5, p < 0.036, respectively). CONCLUSIONS: A
      significant increase in resistin concentration expressed also as resistin/BMI,
      and resistin/adiponectin ratios, observed in children with CF may suggests that
      this adipokine is involved in the inflammatory process underlying the disease and
      is related to worse spirometric parameters describing airways obstruction.

PMID- 29465159
TI  - Physiological responses to swimming fatigue in juvenile largemouth bronze gudgeon
      Coreius guichenoti.
AB  - Stepped velocity tests were conducted on juvenile largemouth bronze gudgeon
      Coreius guichenoti in a swim tunnel respirometer, and oxygen consumption
      increased with swimming speed to fatigue and then decreased during recovery.
      Serum levels of total protein, glucose and triglycerides initially decreased,
      increased at fatigue and then decreased during recovery. Levels stabilized after
      120 min, corresponding to the time necessary to recover from fatigue.

PMID- 29465160
TI  - Pharmacokinetics of orbifloxacin in crucian carp (Carassius auratus) after
      intravenous and intramuscular administration.
AB  - The pharmacokinetics of orbifloxacin was studied after a single dose (7.5 mg/kg)
      of intravenous or intramuscular administration to crucian carp (Carassius
      auratus) reared in freshwater at 25 degrees C. Plasma samples were collected from
      six fish per sampling point. Orbifloxacin concentrations were determined by high
      performance liquid chromatography with a 0.02 MUg/ml limit of detection, then
      were subjected to noncompartmental analysis. After intravenous injection, initial
      concentration of 5.83 MUg/ml, apparent elimination rate constant (lambdaz ) of
      0.039 hr-1 , apparent elimination half-life (T1/2lambdaz ) of 17.90 hr, systemic
      total body clearance (Cl) of 75.47 ml hr-1  kg-1 , volume of distribution (Vz) of
      1,948.76 ml/kg, and volume of distribution at steady-state (Vss) of 1,863.97
      ml/kg were determined, respectively. While after intramuscular administration,
      the lambdaz , T1/2lambdaz , mean absorption time (MAT), absorption half-life
      (T1/2ka ), and bioavailability were determined as 0.027 hr-1 , 25.69, 10.26, 7.11
      hr, and 96.46%, respectively, while the peak concentration was observed as 3.11
      +/- 0.06 MUg/ml at 2.0 hr. It was shown that orbifloxacin was completely but
      relatively slowly absorbed, extensively distributed, and slowly eliminated in
      crucian carp, and an orbifloxacin dosage of 10 mg/kg administered intravenously
      or intramuscularly would be expected to successfully treat crucian carp infected
      by strains with MIC values <=0.5 MUg/ml.

PMID- 29465161
TI  - Assessment of the pharmacological interactions between the nematodicidal
      fenbendazole and the flukicidal triclabendazole: In vitro studies with bovine
      liver microsomes and slices.
AB  - Parasitic diseases have a significant impact on livestock production.
      Nematodicidal drugs, such as fenbendazole (FBZ) or its oxidized metabolite
      oxfendazole (OFZ), can be used along with the trematodicidal triclabendazole
      (TCBZ), to broaden the spectrum of anthelmintic activity. However, co-exposure to
      these compounds could lead to drug-drug (D-D) interactions and eventually alter
      the clinical profile of each active principle. The aim of this study was to
      assess the presence of such interactions by means of two in vitro models, namely
      bovine liver microsomal fractions and bovine precision-cut liver slices (PCLSs).
      To this end, an in vitro assessment involving incubation of FBZ and TCBZ or a
      combination of FBZ and TCBZ was carried out. Results with microsomal fractions
      showed a 78.4% reduction (p = .002) in the rate of OFZ production upon co
      incubation, whereas the sulfoxide metabolite of TCBZ (TCBZSO) exhibited a
      decreasing tendency. With PCLS, OFZ accumulation in the incubation medium
      increased 1.8-fold upon co-incubation, whereas TCBZSO accumulation decreased by
      28%. The accumulation of FBZ and OFZ in the liver tissue increased upon 2-hr co
      incubation, from 2.1 +/- 1.5 to 18.2 +/- 6.1 (p = .0009) and from 0.4 +/- 0.1 to
      1.3 +/- 0.3 nmol (p = .0005), respectively. These results confirm the presence of
      D-D interactions between FBZ and TCBZ. Further studies are needed to determine
      the extent of involvement of drug-metabolizing enzymes and membrane transporters
      in interactions between compounds largely used in livestock production systems.

PMID- 29465163
TI  - The Long History of the Diverse Roles of Short ORFs: sPEPs in Fungi.
AB  - Since the completion of the genome sequence of the model eukaryote Saccharomyces
      cerevisiae, there have been significant advancements in the field of genome
      annotation, in no small part due to the availability of datasets that make large
      scale comparative analyses possible. As a result, since its completion there has
      been a significant change in annotated ORF size distribution in this first
      eukaryotic genome, especially in short ORFs (sORFs) predicted to encode
      polypeptides less than 150 amino acids in length. Due to their small size and the
      difficulties associated with their study, it is only relatively recently that
      these genomic features and the sORF-encoded peptides (sPEPs) they encode have
      become a focus of many researchers. Yet while this class of peptides may seem new
      and exciting, the study of this part of the proteome is nothing new in S.
      cerevisiae, a species where the biological importance of sPEPs has been elegantly
      illustrated over the past 30 years. Here the authors showcase a range of
      different sORFs found in S. cerevisiae and the diverse biological roles of their
      encoded sPEPs, and provide an insight into the sORFs found in other fungal
      species, particularly those pathogenic to humans.

PMID- 29465162
TI  - Radiotherapy-induced morphoea of the breast responding to photodynamic therapy.

PMID- 29465164
TI  - Vacchi's palatal organ: a widespread trait in Holocephali.
AB  - A palatal organ, possibly used for food sorting and processing, has previously
      been identified among the vomerine toothplates of the chimaeroid Chimaera
      monstrosa. In this study, the palatal organ was described in six additional
      species, confirming it is a widespread trait among holocephalans. It is proposed
      that this palatal structure, which appears to differ in shape according to each
      chimaeroid's degree of durophagy and is not homologous to the palatal structure
      described in teleosts, be hereby referred to as Vacchi's organ.

PMID- 29465165
TI  - Validation of the Mood and Feelings Questionnaire (MFQ) and Short Mood and
      Feelings Questionnaire (SMFQ) in New Zealand help-seeking adolescents.
AB  - OBJECTIVE: This study examines the reliability and validity of the Mood and
      Feelings Questionnaire (MFQ) and Short Mood and Feelings Questionnaire (SMFQ) for
      measuring depression in New Zealand help-seeking adolescents. METHOD: A sample of
      183 adolescents completed the 33-item MFQ, which includes all 13 items on the
      SMFQ, at three time points during a trial of a computerized intervention for
      depression. RESULTS: Both the MFQ and SMFQ demonstrated good to excellent
      Cronbach's alphas, moderate to strong item-total score correlations, moderate to
      strong correlations with quality of life and anxiety measures, and strong
      correlations with the clinician-rated Children's Depression Rating Scale-Revised
      and the Reynolds Adolescent Depression Scale 2 at all time points, indicating
      good reliability and content, convergent, and concurrent validities,
      respectively. Favoring sensitivity over specificity, the optimal cut-off value
      for differentiating depressed from nondepressed cases for the MFQ was >=28 and
      for the SMFQ was >=12. Both instruments demonstrated satisfactory diagnostic
      accuracy and sensitivity to change. CONCLUSION: The MFQ and SMFQ are free and
      simple instruments that can be used to identify depression and measure symptom
      change in New Zealand help-seeking adolescents.

PMID- 29465166
TI  - Full percutaneous biventricular support with two Impella pumps: the Bi-Pella
      approach.
AB  - Extracorporeal membrane oxygenation is used for acute respiratory distress
      syndrome, refractory cardiogenic shock, and out-of-hospital cardiac arrest with
      uncertain neurological status, and, until recently, it was the only minimally
      invasive option to achieve biventricular support. However, extracorporeal
      membrane oxygenation increases left ventricular afterload and requires systemic
      anticoagulation, which is a major contraindication in the context of thrombolytic
      therapy following an ischaemic stroke. Conversely, the Impella heart pumps by
      design unload the ventricle and require minimal anticoagulation. We report the
      first case of mechanical circulatory supported with Impella CP on the left and
      Impella RP on the right (Abiomed Inc., Danvers, MA) for acute biventricular
      failure due to suspected acute myocarditis in the context of thrombolytic therapy
      for ischaemic stroke.

PMID- 29465167
TI  - Computer Simulations Reveal a Novel Blocking Mode of the hERG Ion Channel by the
      Antiarrhythmic Agent Clofilium.
AB  - The binding modes of many hERG ion channel blockers are well understood, but a
      notable exception is clofilium, a potent antiarrhythmic agent whose action relies
      on blocking the current mediated by hERG. From the previously hypothesized
      binding modes of clofilium to hERG, only two can explain most of the experimental
      results. In this study, computer simulations are performed in order to analyze
      the hypothesized binding modes and to identify the consensus one. This is
      accomplished by employing molecular dynamics (MD) simulations and interaction
      energy calculations. The results show an unexpected binding mode, in which the
      quaternary nitrogen is placed in the upper part of the inner cavity, interacting
      strongly with Ser624, while the chlorophenyl group is located in the lower part,
      in better agreement with previous experimental results. This novel binding
      position also explains the higher affinity of clofilium for the related hEag1
      channel and was correlated with the possibility that potent hERG blockers
      interact in specific ways with the residues near the intracellular activation
      gate, offering a new explanation that could help predict the potency of other
      hERG-blocking compounds.

PMID- 29465168
TI  - A new species of Sturisoma (Loricariidae: Loricariinae) from the Madre de Dios
      River basin, Peru, with a key to all congeners and comments on the type series of
      Sturisoma rostratum.
AB  - A new species of the genus Sturisoma from the Madre de Dios River, upper Madeira,
      Peru, is described. The new species can be differentiated from its congeners by
      the following characteristics: dorsolateral stripe reaching to less than half, or
      only half length of caudal peduncle (v. absence of dorsolateral stripe or, if
      present, spanning more than half caudal-peduncle length); premaxillary teeth
      longer than dentary teeth (v. dentary teeth longer); sexually mature adult males
      having well-developed odontodes on the sides of the head and a broader snout (v.
      adult males lacking well-developed hypertrophied odontodes or, if present,
      rostrum is same width as females' or immature males'); by having the ventral
      portion of the rostrum conspicuously darker than ventral surface of the body (v.
      rostrum light, with same colour as ventral portion of body, except in Sturisoma
      barbatum); by lacking the lateral process of the sphenotic (v. lateral process of
      sphenotic well-developed, except in Sturisoma tenuirostre); a dark spot on the
      first three branched pectoral-fin rays (v. brown spot absent, except in S.
      barbatum); and the frontal bone contributing less than half of dorsal border of
      the orbital ridge (v. extensive participation of the frontal, except in Sturisoma
      guentheri). Furthermore, the new species has 18-20 plates in the median series,
      which differentiates it from Sturisoma rostratum (21-22), and Sturisoma monopelte
      (21); and 14-15 coalescent plates, which differentiates it from S. tenuirostre
      (16-17). It is further differentiated from Sturisoma brevirostre by presence of
      an enlarged rostrum (v. rostrum not enlarged). A discussion regarding status of
      the type series and geographic distribution of Sturisoma rostratum is offered,
      and an identification key for all Sturisoma species is presented.

PMID- 29465169
TI  - "Time is Brain:" A concept anaiysis.
AB  - Time is brain has been heard echoing in the world of acute stroke since the early
      nineties. At that time, the use of intravenous recombinant tissue plasminogen
      activator (rt-PA) revolutionized the approach to treating acute ischemic stroke.
      However, the use of rt-PA is strongly time dependant, with a narrow window of
      opportunity of only 4.5 hours. There is also convincing scientific evidence of a
      significant relationship between time to rt-PA treatment and patient outcomes.
      Similar to rt-PA in the '90s, time sensitive endovascular therapy has transformed
      the treatment of acute stroke. Hence, time is brain has been referred to as a
      battle cry, with these three words significantly influencing the
      multidisciplinary stroke teams who provide care to stroke victims. Despite
      agreement in the scientific literature that time is brain represents the essence
      of hyperacute stroke care, this concept has not been studied through the
      methodological approach of a concept analysisframework. Therefore, the purpose of
      this concept analysis was to explore the concept of time is brain within the
      context of acute stroke. Walker and Avants (2011) approach to concept analyses
      was used to gain insight into the provision of optimal acute stroke care in
      clinical nursing practice.

PMID- 29465170
TI  - The Importance of Preserving Tax-Preferred Status for Employer-Sponsored Health
      and Retirement Plans.
AB  - The future of employer-sponsored health and retirement plans may be at risk. For
      years, employers have struggled to maintain and pay for these plans despite the
      increasing compliance and financial burdens imposed by legislative and regulatory
      action. Now, as Congress begins to lay the foundation for comprehensive tax
      reform, the need to raise federal revenue may trump the continuation of the tax
      preferences for employer-provided health and retirement benefits. Recent actions
      illustrate that the drive for federal revenue may not be sufficiently tempered by
      the potential negative impact on employers and employees who must bear the brunt
      of these revenue-induced changes. This article considers the erosion of
      protections offered by the Employee Retirement Income Security Act (ERISA) and
      the importance of maintaining the tax treatment of employer-provided benefits.

PMID- 29465171
TI  - Evaluating the Investment Potential of HSAs in Benefit Programs.
AB  - Despite its complexities, the health savings account (HSA) is a powerful and
      growing element of the U.S. financial landscape. In the future, employers will
      likely be expected to provide tax-advantaged savings programs for employees'
      current and future medical expenses. This article discusses investment lineup
      issues that must be addressed in order to optimize HSAs to help participants
      achieve successful outcomes. Plan sponsors at the forefront of addressing these
      issues (and perhaps others) will be in a better position to help their employees
      maximize both the health benefits and the wealth benefits provided for a secure
      retirement.

PMID- 29465172
TI  - Examining the Evolution of Paid Parental Leave.
AB  - While the United States continues to be the only developed nation without
      mandated paid maternity leave, U.S. employers are blazing their own trail for new
      parents. This article defines parental leave, explains what's driving the
      increased interest in paid parental leave among employers offering it and
      discusses how paid parental leave can benefit employers and employees alike.
      Finally, the author discusses why not all employers are offering these benefits
      as well as considerations for employers contemplating whether paid parental leave
      is right for them.

PMID- 29465173
TI  - Collaborative Employee Wellness: Living Healthy With Diabetes.
AB  - Innovative approaches to managing an employee population with a high prevalence
      of type 2 diabetes mellitus can mitigate costs for employers by improving
      employees' health. This article describes such an approach at McCormick &
      Company, Inc., where participants had statistically significant improvements in
      weight, average plasma glucose concentration (also called glycated hemoglobin or
      A1c) and cholesterol. A simulation analysis applying the findings of the study
      population to Maryland employees with a baseline A1c of greater than 6.0% showed
      that participation in the program could improve glycemic control in these
      patients, reducing the A1 c by 0.24% on average, with associated cost savings for
      the employer.

PMID- 29465174
TI  - ERISA Preemptions in Health Plans.

PMID- 29465175
TI  - Disability Benefits Plan's Notice of Denial Defective.

PMID- 29465176
TI  - Nurses' experiences of providing care to bereaved families who experience
      unexpected death in intensive care units: A narrative overview.
AB  - BACKGROUND: Death is a common occurrence in intensive care units (IC Us) and the
      complexity of care makes it difficult for nurses to find a balance between the
      patient's physical needs and the family's emotional needs, especially in
      circumstances of unexpected death. Cumulative or unresolved grief for families
      can have lasting negative repercussions. Nurses, therefore, need access to
      bereavement education in order to provide optimal- bereavement support. PURPOSE:
      The purpose of this review is to identify challenges and facilitators that nurses
      experience in delivering bereavement support during and after sudden or
      unexpected death in ICUs. METHODS: A narrative overview was conducted based on a
      literature search using GINA HL, Medline, Psyclnfo, Scopus, and Pro quest
      databases, as well as grey literature, revealing 241 articles, 15 of which met
      inclusion criteria. FINDINGS: Four themes surrounding bereavement support in the
      ICUs emerged: influence of hospital policies and organizational constraints; sign
      ~tl cance of time and trust; level of knowledge and support of staff and nurses'
      inner conflict, moral distress, and personal ways of coping. CONCLUSION: The
      availability of up-to-date literature in this area is limited. Further research
      could inform organizational poli- cies, nursing education, and nursing staff
      development to address existing barriers. With adequate resources, practical
      strate- gies could be implemented to provide bereavement support that ensures
      optimal bereavement outcomes for families experiencing sudden or unexpected death
      in ICUs.

PMID- 29465177
TI  - End-of-life care in the ICU: Supporting nurses to provide high-quality care.
AB  - ICU care has traditionally focused on curative treatment, but making the decision
      to withdraw life-sustaining therapies, the there is an increasing awareness of
      the key role palliative and barriers to providing good end-of-life care, factors
      that support comfort care play. Through a review of recent literature on end-
      good end-of-life care, and specific guidelinesfor the withdrawal of-life care and
      withdrawal of life-sustaining therapies in the of life-sustaining therapies.
      Using this information, a checklist to intensive care unit, four themes have
      emerged: the challenges of support end-of-life care by critical care nurses was
      created.

PMID- 29465178
TI  - Implementation of a unique RRT model in a tertiary care centre in Western Canada.
AB  - In early 2010, the Royal Alexandra Hospital (RAH) was the only tertiary hospital
      in Edmonton, Alberta, without a rapid response team (RRT). Once funding was
      obtained, the RAH RRT was developed with the mission of "Helping you make it
      happen" with the underlying philosophy that any call is a good call and the team
      is there to support care on the wards. The RAH RRT is unique, as it uses a
      registered nurse/respiratory therapist model rather than the physician model used
      by most tertiary centres. The RAH RRT provides consistent and efficient response
      to deteriorating patients and visitors to the hospital. The RRT does not replace
      the attending team, rather the team supports them to provide improved patient
      care and to escalate care if required. Other major centres in Alberta have heard
      about the success of the RAH model and are moving toward a similar model.

PMID- 29465179
TI  - Workplace Violence and Components of a Psychologically Healthy Workplace.
AB  - As episodes of workplace-centered violence have increased in the United States, a
      focus on emotional and mental health matters is more essential than ever. It is
      imperative for organizations to be proactive about violence prevention and have a
      plan that is supported by top management and understood by all managers and
      employees. Employers can take a number of steps in collaboration with a
      comprehensive violence prevention plan to promote a supportive and safe work
      environment. This article addresses workplace violence, risk factors and the
      components of a violence prevention plan as well as the importance of building a
      psychologically healthy workplace.

PMID- 29465180
TI  - Benefits Innovations in Employee Behavioral Health.
AB  - More and more employers recognize the business impact of behavioral health
      concerns in the workplace. This article provides insights into some of the
      current innovations in behavioral health benefits, along with their rationale for
      development. Areas of innovation include conceptual and delivery models,
      technological advance- ments, tools for engaging employees and ways of
      quantifying the business value of behavioral health benefits. The rapid growth of
      innovative behavioral health services should provide employers with confidence
      that they can tailor a program best suited to their priorities, organizational
      culture and cost limitations.

PMID- 29465181
TI  - Moving Mountains for Mental Health and Well-Being.
AB  - Today, for mental health, it is the best of times, and it is the worst of times.
      The barriers to achieving the mental health system we need are not just a chasm
      of a poorly organized system of care but a mountain range of issues that stop us
      from bringing mental health and well:being into the 21st century on a par with
      the rest of health care. This article reviews the progress that has been made,
      describes the continuing concerns and outlines a path forward toward holistic
      mental health and well-being in the workplace. We have been starting to move
      these mountains, but it is a heavy lift and will require unprecedented dialogue,
      engagement of diverse stakeholders and actions on many fronts to get us to the
      other side.

PMID- 29465182
TI  - Recent Developments in Mental Health Parity.
AB  - Although the Mental Health Parity and Addiction Equity Act (MHPAEA) and
      associated regulations have been around for a while, behavioral health advocacy
      groups have expressed significant concern about a lack of enforcement to ensure
      compliance among health plans and employers. Federal and state governments have
      stepped up efforts to encourage MHPAEA compliance. This article presents recent
      developments in mental health parity, including a summary of the parity law
      requirements, new warning signs for nonquantitative treatment limitations, a
      confusing answer to a frequently asked question from the U.S. Department of
      Labor, an update on enforcement developments and the results of recent Milliman
      research on cost patterns since MHPAEA went into effect.

PMID- 29465183
TI  - Employers Use Stress Diagnostics to Define Strategy and Guide Action.
AB  - Investing time and effort to uncover and mitigate today's stressors for employees
      can help employers avoid tomorrow's more damaging and expensive consequences. A
      comprehensive assessment of workplace stress can generate a substantial return on
      this investment, measured in enhanced individual well-being, reduced health care
      and disability costs and improved company performance. This article discusses the
      structure of stress diagnostics, the dimensions of those diagnostics, leading and
      lagging indicators of employee stress and how employers can use diagnostics to
      take actions that benefit employers and employees alike.

PMID- 29465184
TI  - Opioid Addiction and Implications for Employers.
AB  - Although the prevalence and destruction of opioid addiction have touched
      individuals and families across all social groups and geographies, until
      recently, federal and state-level efforts to confront this growing problem have
      lacked focus and rigor. With several legislative actions already underway and the
      recent enactment of the Comprehensive Addiction and Recovery Act (CARA), we will
      continue to see a focus on program development and treatment strategies.
      Employers can contribute toward curbing the opioid addiction epidemic in a number
      of ways and should play an instrumental role in facilitating increased awareness
      of and access to needed programming. These efforts will improve quality of life
      for employees and their dependents, as well as have a positive impact on
      productivity (including reduced absenteeism and decreased presenteeism). This
      article will explore the size and prevalence of the opioid epidemic, reflect on
      its implications for employers-including public policy initiatives-and suggest
      specific strategies for employer interventions.

PMID- 29465185
TI  - How Perceptions of Mental Illness Impact EAP Utilization.
AB  - Studies of employee assistance program (EAP) clinical use across multiple
      industries and multiple EAP delivery models range from highs greater than 5% to
      lows of less than 1 %. Despite the range in utilization, the rates of employee
      behaviors that indicate a behavioral health issue are significantly higher,
      suggesting far too little use of EAPs overall. Studies of the costs to an
      employer for an employee with a mental health issue are as high as 37% lost
      annual productivity. EAPs have attempted to raise utilization through a variety
      of efforts, with mixed results. Most EAP utilization initiatives fail to address
      the impact of stigma, misunderstandings about mental illness and the reluctance
      of many employees to seek counseling as an option for better management of
      stress, work-life balance and overall mental wellness. For both employers and
      EAPs, addressing the impact of stigma and perceptions of mental illness is
      costly, requiring greater direct employee engagement and education. However, it
      is a more effective means of increasing EAP use than current practices and,
      ultimately, can result in significantly higher net gains in productivity while
      reducing employers' direct costs.

PMID- 29465186
TI  - Pharmacogenetic Testing May Improve Drug Treatments and Shorten Disability
      Leaves.
AB  - This article describes how methods of personalized medicine-specifically,
      pharmacogenetic (PGx) testing-can benefit private health plans, benefits
      managers, care providers and consumers alike. The authors cover pharmacogenomics
      as a science and also introduce an innovative way to optimize drug treatments.
      The article touches on some important clinical outcomes drawn from a recent study
      in community pharmacy and reviews the application and return on investment of PGx
      testing in disability and medication management.

PMID- 29465187
TI  - Return-to-Work Strategies for Employees With Mental Health Conditions.
AB  - There's no question that employers can no longer ignore mental health issues.
      Compassion and support for employees aside, it is simply good business to protect
      the mental health and productivity of employees. This article describes existing
      challenges surrounding employees with mental disorders: the link between mental
      disorders, disability and an employee's ability to return to work; best practices
      for employers, employees and health care providers; and the role of the insurance
      company. Together, using proven strategies, everyone contributes to the optimal
      solution of helping employees with mental disorders return to work.

PMID- 29465188
TI  - Bringing Workforce Health to the Top Line-Expanding the Value Proposition for
      Workforce Health Improvement.
AB  - The pressure on employers to justify providing health benefits or to prove the
      value of health investment has never been greater. Many employers have resorted
      to cost shifting to employees to dampen the impact of health care costs on their
      companies or have avoided health investments, believing they don't deliver a
      return. Both strategies come with significant risk to employees, their dependents
      and the company's business performance. This article provides a framework for
      employers to better understand the full impact of workforce health and well-being
      on bottom-line costs and the opportunities for connecting workforce health and
      well-being to topline business performance metrics. Application of the principles
      presented in this commentary can help human resources/benefits personnel better
      understand the broader business impacts of their workforce health and well-being
      strategies as well as equip them to have a more meaningful role in workforce
      strategic planning.

PMID- 29465189
TI  - Third Party Lacks Standing Under MHPAEA.

PMID- 29465190
TI  - ERISA Preempts Action in Benefits Denial.

PMID- 29465191
TI  - Emotional Distress Claim Can Overcome ERISA Preemption.

PMID- 29465192
TI  - Mental Health and Substance Abuse Benefits Benchmarked.

PMID- 29465193
TI  - Ideas for Improving Retirement Wellness.
AB  - Employers can and should take steps to support retirement and financial wellness.
      This article provides a framework for retirement wellness informed by research
      conducted or supported by the Society of Actuaries. Research insights about
      Americans' finances, planning, decisions, money management, debt, retiree income
      shocks and other areas point to ways employers can provide retirement wellness
      support as a vital part of an overall benefit program. The author suggests
      several key considerations employers should pay attention to in order to improve
      retirement wellness.

PMID- 29465194
TI  - Workplace Financial Wellness Programs Help Employees Manage Health Care Changes.
AB  - Employers and employees are navigating major changes in health insurance
      benefits, including the move to high-deductible health plans in conjunction with
      health savings accounts (HSAs). The HSA offers unique benefits that could prove
      instrumental in helping workers both navigate current health care expenses and
      build a nest egg for much larger health care costs in retirement. Yet employees
      often don't understand the HSA and how to best use it. How can employers help
      employees make wise benefits choices that work for their personal financial
      circumstances?

PMID- 29465195
TI  - Health Savings Accounts: An Emerging Cornerstone of the Health-Wealth Bridge?.
AB  - Several trends may help make health savings accounts (HSAs) a ubiquitous part of
      Americans' financial planning. When one looks at the totality of factors, it is
      easy to see how HSAs can become a vital connection be- tween active and retiree
      health care needs and between retirement income and retiree medical needs.
      However, it is also easy to see the clouds over the horizon that could stall HSA
      growth in coming years. This article discusses both.

PMID- 29465196
TI  - The HSA in Your Future: Defined Contribution Retiree Medical Coverage.
AB  - In 2004, when evaluating health savings account (HSA) business opportunities, I
      predicted: "Twenty-five years ago, no one had ever heard of 401(k); 25 years from
      now, everyone will have an HSA." Twelve years later, growth in HSA eligibility,
      participation, contributions and asset accumulations suggests we just might
      achieve that prediction. This article shares one plan sponsor's journey to help
      employees accumulate assets to fund medical costs-while employed and after
      retirement, It documents a 30-plus-year retiree health insurance transition from
      a defined benefit to a defined dollar structure and culminating in a full
      replacement defined contribution structure using HSA-qualifying high-deductible
      health plans (HDHPs) and then redeploying/repurposing the HSA to incorporate a
      savings incentive for retiree medical costs.

PMID- 29465197
TI  - Challenges Facing U.S. Long-Term Care Financing: Future Needs, Key Issues and
      Current Solutions.
AB  - The need for long-term care (LTC) is on the rise as the Baby Boomer generation
      ages. This article will focus on the projected future drivers and costs for LTC,
      why the private LTC approach has not worked to date and alternate approaches in
      the market that appear to help address some of the current needs.

PMID- 29465198
TI  - [EPISTAXIS DURING NASOTRACHEAL INTUBATION. ATTILA'S SYNDROME.]
AB  - BACKGROUND: Nasal bleeding is a common complication during nasotracheal
      intubation (NTI). This is due to the ana- tomical prerequisites and the
      hemostatic system failure. Using of various research methods in practice can
      reduce the frequency of such complications. The purpose of the study is to
      identify predictors of high probability of epistaxis associated with the NTI and
      the pecu- liarities of the anatomical mucous membrane structure of the nasal
      passages, and to assess significance of blood coag- ulationfailures in these
      cases. MATERIALS AND METHODS: 45 patients (f-25 and m-20), aged 23 to 47 years,
      with physical status I-IIASA were analyzed. Depending on the degree of surgical
      trauma manipulation during intubation were formed three groups of patients in
      whom the NTI was atraumatic, moderately traumatic and overly traumatic. During
      preoperative period all patients underwent a rhinoscopy. Intubation trauma of the
      trachea was assessed by visual analogue scale. The results and discussion. The
      study of the nasal mucosa structure showed that with atraumatic intubation (Group
      1; n=9) were dominated by deep type of bedding nonplethoric nonkinking vessels
      (66.7% ofpatients (n=6)). During mod- erate trauma intubation (Group 2; n=24),
      superficial and deep vessels were found equally (50% and 50%). In patients with
      severe trauma during intubation (Group 3; n=13), 100% of the patients, the
      vessels were located superficially, 75 % were convoluted, plethoric, mucosa
      contact bleeding. There were no anatomical changes. CONCLUSION: The source of
      bleeding are superficial, plethoric, kinking vessels of the mucous membrane.
      Hypocoagu- lation disorders, observed in patients during reconstructive
      surgeries, exacerbate such bleeding and can lead to fatal complications.

PMID- 29465199
TI  - [INJURY PREVENTION WHILE ENSURING THE AIRWAY DURING SURGERY IN THE NOSE AND
      SINUSES.]
AB  - THE AIM: A comparative analysis of the injuries of upper airways flexible
      reinforced laryngeal mask and endotracheal intubation by examining the stress
      response reaction of the cardiovascular system, as well as the frequency and
      variety of complications. Blood pressure, heart rate, glucose and cortisol, and
      complications of airway management in children were analyzed. METHODS: The
      influence of the method of airway management with surgery in nose and sinuses in
      children in the stress response, hemodynamics, injuries of the airway were
      studied. The study included 140 patients aged 3 to 17 years. RESULTS: LMA
      FlexibleTMhas a minimal negative impact on the hemodynamics. Stress response is
      less pronounced when installing laryngeal mask than with tracheal intubation,
      which manifests itself in less cortisol concentration of 3.7%, 11.4% glucose.
      After removing the flexible reinforced laryngeal mask less than after extubation
      occurs: cough by 21%, 10% hoarseness, and sore throat by 26%. CONCLUSION: The use
      of the laryngeal mask airway during surgery in the nose and paranasal sinuses
      safer and less trau- matic manipulation compared with tracheal intubation.

PMID- 29465200
TI  - [THE CHOICE OF TRACHEAL INTUBATION METHOD IN RECONSTRUCTIVE MAXILLO-FACIAL
      SURGERY WITH DIFFICULT AIRWAYS.]
AB  - BACKGROUND: The development of modern video - and endoscopic equipment allows for
      revision and adjust to modern protocols for maintaining patency of the difficult
      airway, especially in maxillofacial or ENT -surgery. THE PURPOSE OF THE STUDY:
      Comparison the efficacy ofvarious methods of maintaining the airway patency in
      the practice of reconstructive maxillofacial surgery. MATERIALS AND METHODS: 89
      patients, who were divided into 4 groups, were examined. Group I (n=57) - classic
      laryngos- copy with the Macintosh blade, group II (n=14) -fiber-optic
      bronchoscopy (FBS) in clear consciousness. In group III (n=10) tracheal
      intubation was performed by the blade D-Blade of videolaryngoscope C-MAC (Karl
      Storz) or McGrath (Aircraft Medical Ltd.). In group IV (n=12) - retromolar
      endoscope (RAE) intubation by videostylet Shikani (Clarus Medical) and RME
      Bonfils (Karl Storz). At the time of laryngoscopy and tracheal intubation the
      duration of tracheal intubation (t), the maximum values of arterial blood
      pressure and heart rate, galvanic skin response (GSR) (NASTYA, Neyrok, Russia)
      were analyzed. The results and discussion. Unexpected difficult tracheal
      intubation occurredfor 31.6 % of the 1st group patients, need two attempts at
      laryngoscopy and tracheal intubation occurred in the subgroup 1B patients at 61.1
      % (n=11), three at- tempts at 33.3 % (n=6), more than three attempts at 5.6%
      (n=1). FBS is the method of choice in patients with a planned difficult
      intubation, in cases of facial skeleton severe deformations . At the same time,
      local anesthesia and sedation is not capable ofproviding psycho-emotional comfort
      forpatients during FBS procedure. Visualization in 100% of the hy- popharynx
      structures at the McCormack I-II degree when using the blade D-Blade is appeared.
      The use of RME should not be recommended for routine planned and especially
      unexpected emergency difficult intubation. CONCLUSION: Comparison of methods of
      maintaining the airway allows to adjust the plan of sequential actions in
      difficult intubation, both planned and in an emergency situation. The
      effectiveness of blades type D-Blade is confirmed. In patients with facial skull
      deformity and impaired mouth opening (less than 1.3 cm) method of choice is awake
      intubation by fibrobronchoscope. The use if retromolar intubation is also
      justified, but this method may be accompanied by a lot number of failures.

PMID- 29465201
TI  - [PULSE WAVE TRANSIT TIME - ONE MORE ATTEMPT OF NON-INVASIVE CARDIAC OUTPUT
      MEASUREMENT.]
AB  - BACKGROUND: Estimated continuous cardiac output (esCCOTM) based on pulse wave
      transit time is one of alternative non-invasive CO measurement techniques.
      METHODS: Randomized study included 23 scheduled patients operated upon due to
      cardiovascular diseases. Cardiac index (CI) was measured Comparative analyses of
      esCCO and others CO measurement methods used intraoperative was carried out. In
      the first group (n = 9) esCCO was compared with transpulmonary thermodilution
      (PiCCO-plus); in the second group (n = 8) - with pulmonary artery thermodilution;
      in the third group (n = 6) - with transoesophageal echocardiography (velocity
      time integral). RESULTS: In the 1st group direct correlation was found (r =
      0,773, p <0.0001), but overestimation was found in 39% of cases; underestimation
      in 4%. The 2nd group showed direct correlation (r = 0.586, p <0.0001). The 3d
      group showed direct relationship (r = 0.68, p = 0.0018), but 66.7% of the
      measurements were out of reference interval (more than ? 15%). Blend- Altman
      method showed the dispersion of results in all groups. CONCLUSIONS: 1. Estimated
      continuous cardiac output measurement technique based on PWTT has a direct
      correla- tion with prepulmonary thermodilution and transoesophageal
      echocardiography, medium and high power respectively. 2. esCCO has significant
      differences with the referential techniques during general anesthesia in cardiac
      surgery pa- tients. 3. Calibration based on invasive blood pressure and outside
      cardiac output measurement does not increase the accuracy of measurements. 4.
      esCCO has a negative diagnostic value and cannot be recommendedfor the cardiac
      out- put evaluation during cardiac surgery. 5. This method can be useful for
      analyze general effectiveness of perioperative hemodynamics.

PMID- 29465202
TI  - [LUNG ULTRASOUND IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES AND ACUTE
      RESPIRATORY FAILURE DUE TO PNEUMONIA.]
AB  - PURPOSE: To compare the accuracy of bedside lung ultrasound (LUS) and chest
      computed tomography (CT) for the de- tection of lung lesions in patients with
      hematological malignancies and acute respiratory failure (ARF). MATERIALS AND
      METHODS: 39 patients with hematological malignancies and ARF were enrolled in
      prospective study. The investigation of the patients included LUS, chest C,
      extravascular lung water index (EVLW) by transpulmonary ther- modilution, and
      bronchoalveolar lavage (BAL). RESULTS: There was correlation between the total
      number of B-lines and E VLW index (r = 0,40; p <0,05). The sensitivity,
      specificity of LUS in the total number of B-lines were 78% and 70%, respectively
      (and A UC 0,7). There were correla- tions between A-lines and volume of
      hyperaerated lung regions (r = 0,40; p <0,05) and normally ventilated (r = 0,60;
      p = 0,001) regions, between A-lines and the total lung volume (r = 0,50; p =
      0,001), between A-lines and volume of poorlyventilated lung regions (r = -0,40; p
      = 0,001), A-lines and weight of normally ventilated lung regions (r = 0,50; p =
      0,001), A-lines and weight of poorly ventilated regions (r = -0,35; p <0,05),
      total count of B-lines and volume of poorly ventilated lung regions (r = 0,4; p =
      0,001), between total count of B-lines and weight poorly ventilated lung regions
      (r = 0,4; p = 0,001). There were associations between USfeathers and etiology
      ofpneumonia. A-lines were often detected in patients with gram-negative bacterial
      pneumonia and fungal pneumonia more than in patients with pneu- mocystis
      pneumonia. B-lines were detected often in patients with Pneumocystis pneumonia.
      Sensitivity ofLUS pleural effusion assessment was 95%, specificity was 90%.
      CONCLUSION: LUS is high sensitivity and specificity method to detect lung lesions
      in patients with ARF.

PMID- 29465203
TI  - [USE OF PROTECTIVE LUNG VENTILATION REGIMEN IN CARDIAC SURGERY PATIENTS.]
AB  - BACKGROUND: In cardiac surgery, protective lung ventilation and/or preventive
      brdnchoscopy (PB) are able to decrease lung injury effects of cardiopulmonary
      bypass (CPB) and mechanical ventilation. OBJECTIVES: define lung complication
      risks, evaluate the effect ofprotective lung ventilation (PLV) on lung
      functioning, and investigate the feasibility ofpreventive PB in higher pulmonary
      risk (PR) patients. MATERIALS AND METHODS: 66 patients participated in
      prospective randomized research. Allocation was based on PR and intraoperative
      mechanical ventilation type. PLV includedfollowing parameters: PCK PIP - up to 20
      cm H20, Vt - 6 ml/ kg of PBW, PEEP - 5-10 cm H20, IE ratio - 1:1.5-1:1, EtCO2 -
      35-42 mm Hg, FiO2 - 45-60%, lung ventilation during CPB, alveolar recruitment.
      Four groups were formed: A - higher PR plus PLV- B - higher PR plus conventional
      LV (CLV), C - lower PR plus PLV- D - lower PR plus CLV PIP PEEP dynamic
      compliance, p/f ratio and intrapulmonary shunt (Qs/Qt) were recorded. Seventeen
      patients of group A underwent PB. RESULTS: Advanced dynamic compliance, higher
      p/f ratio and lower Qs/Qt were seen in group A, in comparison with group B (p<
      0.05). Lower Qs/Qt was seen in group C, in comparison with group D (p<0.05).
      Mucus obstruction of subsegmental bronchi was observed in 53.3% of higher PR
      patients. More than half ofpatients without PB sufferedfrom postoperative lung
      complications (70.4 vs. 34.2 7%, p<O.05). CONCLUSION: Patients are able to
      successfully assigned to pulmonary risk groups based on our protocol. Protective
      lung ventilation improves lung biomechanics and oxygenating function in higher
      risk patients and decreases intrapulmonary shunt fraction in higher and lower
      risk patients. Addictive preventive bronchoscopy can be successfully used in
      higher risk patients.

PMID- 29465204
TI  - [DIAGNOSTIC VALUE OF THE HOMEOSTASIS PARAMETERS IN SEPSIS DETECTING IN PATIENTS
      WITH INFECTIOUS-INFLAMMATORY COMPLICATIONS DURING THE POSTOPERATIVE PERIOD.]
AB  - : Purpose of the study was to define the diagnostic value of clinical and
      laboratory criteria of sepsis during the postop- erative period Methods. The
      results of 269 blood tests (biochemical, coagulation, hematology and
      microbiology) which were per- formed in 115 patients in the early postoperative
      period (starting from the first postoperative day) and in the late post-
      operative periods were analyzed. RESULTS: Presepsin and procalcitonin have a
      similar diagnostic sensitivity in detection of sepsis - 89% (Psp>328.5 ng/l,
      PCT>1 ng/ml), but presepsin have a statistically significant lower specificity in
      comparison with procalcitonin (31% and 61%, respectively). This fact limits the
      use of presepsin in routine practice in multidisciplinary surgical hospital.
      Quantitative determination ofprocalcitonin is most preferably for the detection
      of septic complications in patients in the postoperative period, the results
      ofpresepsin must be interpreted only with other biochemical and hematological
      parameters.

PMID- 29465205
TI  - [PARTICIPATION OF AROMATIC MICROBIAL METABOLITES IN THE DEVELOPMENT OF SEVERE
      INFECTION AND SEPSIS.]
AB  - : Background Actuality of the problem of infection in critically ill patients
      remains high. Addition a local infectious processes have a tendency to rapid
      generalization and sepsis. Neutrophilsfunction failure plays a key role in the
      patho- genesis of infectious complications and sepsis. The hypothesis about the
      role of microbial metabolites in the formation of immunosuppression, in
      particular in the inhibition of phagocytic activity of neutrophils as the first
      line of defense against bacteria is acquiring more and more supporters. Among the
      microbial metabolites aromatic compounds, such as phenylcarbinol acid (PCA) are
      of particular interest. Their concentration in the blood reaches a maximum in
      case of generalized infection, and correlates with mortality in patients in
      critical conditions, and PCA biological activity confirmed by earlier researches
      in vitro. The purpose of the study was to reveal the relationship of the PCA with
      the severity of bacterial infections and to assess the effect of PCA on
      neutrophils phagocytic activity. MATERIALS AND METHODS: At the first stage the
      levels of PCA (GCh-FID method) in the serum ofpatients (n=57) with a documented
      bacterial infection of varying severity, confirmed APACHE II and SOFA scales were
      analyzed comparing with healthy donors (n=72). During the second stage the effect
      of clinically-relevant concentrations of PCA on neutrophils phagocytic activity
      ofperipheral blood was analyzed in vitro. RESULTS: The levels ofphenylacetic
      (PAA), phenyllactic (PLA), hydroxyphenylacetic (p-HPAA) and hydroxyphenyllactic
      (p-HPLA) acids in patients were significantly higher than in healthy donors,
      reaching the highest values in severe infection. High direct correlation of PCA
      levels with the indicators ofscales APACHE II and SOFA was detected. A
      significant decrease in the number ofphagocytic neutrophils under the influence
      PAA, p-HPAA and PLA was identified in vitro experiment on average 11%. The most
      significant influence p-HPAA, PLA and p-HPLA have made on the intensity of the
      neutrophils absorption capacity reducing this parameter by an average of 26%.
      Also noted that phenylpropionic acid (PPC) which is in blood of healthy donors,
      disappears in critical ill patients. CONCLUSION: Phenolcarbonic acids level in
      the blood serum shows the severity of bacterial inflammatory process. Ex-
      periment in vitro shows that the PCA in clinically-relevant concentrations is
      able to suppress the neutrophilsphagocytic activity.

PMID- 29465206
TI  - [PREDICTORS OF UNFAVORABLE OUTCOME IN PATIENTS WITH ABDOMINAL SEPSIS.]
AB  - OBJECTIVE: The study focuses on identifying predictors of treatment outcome in
      abdominal sepsis (AS) in humans. SUBJECTS AND METHODS: 70 patients underwent
      determination of blood pressure, heart rate, SpO , the content of leu- kocytes,
      albumin, C-reactive protein, fibrinogen and TNF-a in arterial (femoral artery)
      and venous (subclavian vein) blood. Automatic biochemical analyzer Cobas-Integra
      400 ('Roche", Switzerland), the test system Microlab STAR ELISA kit reagents
      "alpha TNF - ELISA - best" were used during the research. System statistical
      analysis included paired comparison of patients with favorable (n=27) and lethal
      (n=43) outcome, correlation, cluster; discriminating analysis, multidimensional
      scaling and plotting ROC curves with sensitivity and specificity indicators
      predictive value. RESULTS: Identfied predictors of outcome inpatients,from which
      to form a predictive model of CRP fibrinogen, albumin, and TNF-a arterial blood.
      It is established that if the basic treatment of the patient CRP <9,8
      g/l,fibrinogen >3,43 g/l, albumin <28,9 gl and TNF-a <499,3 ng/ml, the
      probability of death was statistically significantly higher thanfavorable.
      CONCLUSION: It is assumed that therapeutic measures should be aimed at correction
      of the above mentioned indicators.

PMID- 29465207
TI  - [THE CHOICE OF PERIOPERATIVE MULTIMODAL ANALGESIA IN PATIENTS WITH LUMBAR
      HERNIATED DISC: THE PRELIMINARY RESULTS.]
AB  - DESIGN: 129 patients scheduled for elective lumbar discectomy in 2010-2013 were
      enrolled in prospective study. Group K (n=20) underwent general anaesthesia and
      postoperative analgesia on-demand. Group PMA+SA (n=23) got subarachnoid block and
      preventive multimodal analgesia (PMA) including ketoprofen, paracetamol and
      nalbuphine. At PMA group (n=21) general anaesthesia and PMA were used; at PMA+I
      (n=21) also bupivacaine wound infiltration was administrated; at PlvL4+S (n=20) -
      depo-corticosteroid was applied locally on affected spinal nerve root; at PMA+IS
      (n=24) wound infiltration and local corticosteroids were combined. Patients could
      use i.v. nalbuphine on-demand by PCA device in addition to PMA post-operatively.
      7 days post-operatively, the pain scores using 10 cm VAS at rest and during
      movement were also recorded. RESULTS: Group K patients had not adequate pain
      relief during 4 postoperative days. At PMA group the postoperative analgesia was
      adequate during the whole assessment time, PMA group patients had significant
      less pain scores than at K group during 4 postoperative days. Patients at PM +SA
      had better than PMA group pain relief only during 2 hours postoperatively. Groups
      PMA+I and PMA+IS did not demand nalbuphine at al. Their pain scores were
      signifcant less than at PMA group during 2 postoperative days. CONCLUSIONS:
      Postoperative analgesia on-demand is not adequate but the PMA is. Subarachnoid
      block results in decreasing severity of pain only during first hours
      postoperatively. The additional bupivacaine wound infiltration in pa- tients with
      lumbar herniated disc follows avoiding of opioids and significant pain relief
      during 2 postoperative days.

PMID- 29465208
TI  - [MODERN VIEWS ON THE PHARMACOGENETICS OF PAIN.]
AB  - Quality anesthesia during surgery and in the postoperative period remains a
      topical problem of modern anesthesiology. The study of genetic characteristics of
      a patient is a goal that may be allow us to develop a personalized approach to
      solve this problem. The purpose of the review is a synthesis of literature data
      about the influence of genetic factors on pain perception and its treatment. The
      review included information obtained from SCOPUS, MedLine, EMBASE. The search
      keywords were: pain, pharmacogenetics, polymorphism, analgesics.Describe the
      effect ofgene polymorphisms of OPRM, 5HTRIA, 5HTR2A, COMT GCHI, SCN9A, KCNSI,
      CACNA2D3, CACNG2, PTGSI, PTGS2, MDRJ/ABCB] on the perception of pain, and CYP2D6,
      CYP2C9, CYP3A4 on the pharmacokinetics and pharmacodynamics of medi- cations used
      in the treatment of pain.

PMID- 29465209
TI  - [MITOCHONDRIA-TARGETED ANTIOXIDANTS IN THE PREVENTION OF THE CORNEA EROSION WHEN
      PERFORMING SURGERY UNDER GENERAL ANESTHESIA.]
AB  - : Despite the use of modern methods of prevention, at least 10% of patients
      operated on for ophthalmic indications not develop corneal erosion as the
      indirect complication of general anesthesia. OBJECTIVE: To reduce the number of
      ophthalmic complications of general anesthesia by prophylactic use of new mito-
      chondria-targeted antioxidants - Vizomitin (eye drops). MATERIALS AND METHODS: 70
      patients, which was supposed to perform the average duration of operations under
      general anesthesia were randomized into 3 groups depending on the method specific
      (pharmacological) prevention of corneal erosions: (1) control (specic
      (pharmacological) prevention was not carried out), (2), using preparation
      "natural tear, and (3) "Vizomitin" preparation. Postoperative biomicroscopy was
      performed to assess the condition of the cornea, tear film stability was measured
      and the height of the tear meniscus. RESULTS: When using eye drops "Vizomitin"
      value is an indicator of stability of the tear film on the 3rd day after the
      operation more than in the control group of patients by 51% (p = 0.012) and
      patients groups, natural tear by 57% (p = 0.013). Surgical interventions
      performed under general anesthesia, leading to an increase in the number
      ofpatients with decreased tear meniscus height index of the control group with 4
      to 7 patients (p = 0.30) in the group of natural tear from 3 to 11 patients (p =
      0.008) . In the group with drug "Vizomitin" the number of such patients is
      reduced from 7 to 1 (p = 0.018). CONCLUSION: In the surgical procedures under
      general anesthesia eye drops "Vizomitin" effectively prevents the devel- opment
      of corneal erosion.

PMID- 29465211
TI  - [CASE REPORT: PNEUMOCEPHALIA AFTER EPIDURAL ANESTHESIA FOR HIP REPLACEMENT
      SURGERY.]
AB  - Lumbar epidural anesthesia is a commonly used anaesthetic technique for trauma
      and orthopedic surgery of the lower extremities. One of the rare complications of
      epidural anesthesia is pneumocephalia. The article describes a case of
      pneumocephalia after epidural anesthesia performed for anesthetic management of
      the hip replacement surgery. Eight hours after the epidural anesthesia the
      patient had depression of consciousness progressing to coma. Computed tomog-
      raphy of the brain detected pneumocephalia. Symptomatic treatment provided a
      regression of neurological deficit. CT scanning of the brain on the 8th
      postoperative day showed resolution ofpneumocephalia. The patient was discharged
      from the hospital on the 15th day after surgery. The most probable mechanism
      explaining this case ofpneumocephalia development is the theory ofa the inverted
      bottle).

PMID- 29465210
TI  - [CORRECTION ENERGY DEFICIENT STATES AS POSSIBLE PERIOPERATIVE ADAPTATION OF
      CANCER HEPATOPANCREATODUODENAL ZONE PATIENTS.]
AB  - The aim of this study was to determine the role remaxol in complex intensive
      therapy of various jorms gipoergosis dur- ing the perioperative period in
      patients with hepatopancreatoduodenal zone malignancies. The treatment of 48
      patients was analyzed. Immediately prior to surgery, at random, patients were
      divided into primary (n = 26) and control group (n = 22). In the study group for
      compensation the energy deficient states and organ hypoxia in the pancreas and
      the liver during the intra- and postoperative periods remaxol was included in the
      infusion therapy, the introduction ofwhich had been began before the start of
      anesthesia. In the control group antihypoxants weren't used. Integral assessment
      of prognosis and severity on a scale SAPS II and APACHE II. Status of energy and
      the type of energy deficit was estimated by the transport of oxygen and the
      concentration of lactate. In order to determine the level of stress exposure and
      the for- mation of adaptive reactions examined quantitative and qualitative
      composition of the peripheral blood. The study was conducted prior to surgery, on
      the 2nd and 5th day perioperative period. Inclusion in the scheme of metabolic
      remaxol program in the perioperative period in patients with malignant diseases
      of hepatopancreatoduodenal zone promotes the reduction of different types
      ofgipoergosis, efficient delivery and oxygen consumption, the adequacy of tissue
      oxygenation and restoration of adaptive physiological reactions such as.

PMID- 29465212
TI  - Exploring emergency nurse practitioners' perceptions of their role.
AB  - : Since the 1980s, the emergency nurse practitioner (ENP) role has evolved as
      increasing socioeconomic pressures and changing government policy have led to new
      working practices in emergency departments. Similarly, a lack of consensus
      regarding educational support for ENPs and the regulation of ENP training, mean
      that variations remain in the scope of practice, role description and academic
      requirements for ENPs. AIM: To explore ENPs' perceptions of their changing role,
      including their educational requirements and whether their training needs are
      being met. METHOD: This qualitative phenomenological study examined the views of
      six ENPs using semi-structured interviews. FINDINGS: The study identified four
      themes: inadequate protected time for continuing professional development (CPD);
      importance of senior medical support in role expansion and CPD; inconsistent
      educational preparation for expanded roles; and the ENPs' perceived reasons for
      role expansion. Although all the participants stated that it was challenging to
      find time for CPD when working in busy clinical environments, this was regarded
      as less important than the positive effect of senior medical support for advanced
      roles. CONCLUSION: Over the past three decades, the ENP role has become well
      established, which has led to increased confidence, and the development of
      collaborative ways of working, among ENPs and their colleagues. However, while
      ENPs have embraced the challenges of their changing role, educational support has
      not been consistent. There are still disparities in ENPs' scope of practice,
      expectations of the role between services, and the educational preparation
      required to undertake the role.

PMID- 29465213
TI  - Preventing and managing challenging behaviour.
AB  - Patients exhibiting challenging behaviour, which includes any non-verbal, verbal
      or physical behaviour, is a significant issue in healthcare settings. Preventing
      such behaviour and the harm it can cause is important for healthcare
      organisations and individuals, and involves following a public health model
      comprised of three tiers: primary, secondary and tertiary prevention. Primary
      prevention aims to reduce the risk of challenging behaviour occurring in the
      first instance; secondary prevention involves reducing the risk associated with
      imminent challenging behaviour and its potential escalation; and tertiary
      prevention focuses on minimising the physical and emotional harm caused by
      challenging behaviours, during and after an event. De-escalation should be the
      first-line response to challenging behaviour, and healthcare staff should use a
      range of techniques - maintaining safety, self-regulation, effective
      communication, and assessment and actions - to reduce the incidence of
      challenging behaviour. In some situations, physical interventions may be required
      to protect the safety of the individual, healthcare staff and other individuals
      involved, and healthcare staff should be aware of local policies and procedures
      for this. Following a serious incident, where there was potential or actual harm
      to patients and healthcare staff, healthcare organisations should use post
      incident reviews to learn from the situation, while healthcare staff should be
      offered the opportunity for debriefing. Positive responses to challenging
      behaviour at an organisational and individual level can lead to improved work
      environments for healthcare staff and optimal patient care and outcomes.

PMID- 29465214
TI  - Delivering Public Health Insurance Through Private Plan Choice in the United
      States.

PMID- 29465215
TI  - Selection in Health Insurance Markets and Its Policy Remedies.

PMID- 29465216
TI  - The Questionable Value of Having a Choice of Levels of Health Insurance Coverage.

PMID- 29465217
TI  - Scaling for Economists: Lessons from the Non-Adherence Problem in the Medical
      Literature.

PMID- 29465218
TI  - Population Control Policies and Fertility Convergence.

PMID- 29465220
TI  - Alzheimer's Disease, the "One-Molecule, One-Target" Paradigm, and the Multitarget
      Directed Ligand Approach.
AB  - No selective drugs exist, and we have been designing, synthesizing, and
      evaluating multitarget-directed ligands since the beginning of modern medicinal
      chemistry, without knowing it, most possibly. The challenge to discover the
      efficient Multi-Target Small Molecules (MTSMs) for Alzheimer's disease (AD)
      therapy implies to identify the key combination of biological targets to modulate
      them, thus including in the design the corresponding pharmacophoric groups able
      to do it. Universal and polyvalent pharmacophoric groups, able to modulate
      diverse receptors or enzymatic systems, would simplify the drug discovery process
      leading to new and more efficient MTSMs for AD.

PMID- 29465221
TI  - Polydopamine Surface Chemistry: A Decade of Discovery.
AB  - Polydopamine is one of the simplest and most versatile approaches to
      functionalizing material surfaces, having been inspired by the adhesive nature of
      catechols and amines in mussel adhesive proteins. Since its first report in 2007,
      a decade of studies on polydopamine molecular structure, deposition conditions,
      and physicochemical properties have ensued. During this time, potential uses of
      polydopamine coatings have expanded in many unforeseen directions, seemingly only
      limited by the creativity of researchers seeking simple solutions to manipulating
      surface chemistry. In this review, we describe the current state of the art in
      polydopamine coating methods, describe efforts underway to uncover and tailor the
      complex structure and chemical properties of polydopamine, and identify emerging
      trends and needs in polydopamine research, including the use of dopamine analogs,
      nitrogen-free polyphenolic precursors, and improvement of coating mechanical
      properties.

PMID- 29465219
TI  - Continuous Supply of Plasmodium vivax Sporozoites from Colonized Anopheles
      darlingi in the Peruvian Amazon.
AB  - In vitro culture of Plasmodium vivax liver stages underlies key understandings of
      the fundamental biology of this parasite, particularly the latent, hyponozoite
      stage, toward drug and vaccine development. Here, we report systematic production
      of Plasmodium vivax sporozoites in colonized Anopheles darlingi mosquitoes in the
      Peruvian Amazon. Human subject-derived P. vivax-infected blood was fed to
      Anopheles darlingi females using standard membrane feedings assays. Optimizing A.
      darlingi infection and sporozoite production included replacement of infected
      patient donor serum with naive donor serum, comparing anticoagulants in
      processing blood samples, and addition of penicillin-streptomycin and ATP to
      infectious blood meals. Replacement of donor serum by naive serum in the P. vivax
      donor blood increased oocysts in the mosquito midgut, and heparin, as
      anticoagulant, was associated with the highest sporozoite yields. Maintaining
      blood-fed mosquitoes on penicillin-streptomycin in sugar significantly extended
      mosquito survival which enabled greater sporozoite yield. In this study, we have
      shown that a robust P. vivax sporozoite production is feasible in a malaria
      endemic setting where infected subjects and a stable A. darlingi colony are
      brought together, with optimized laboratory conditions.

PMID- 29465222
TI  - DNA Nanotechnology-Enabled Drug Delivery Systems.
AB  - Over the past decade, we have seen rapid advances in applying nanotechnology in
      biomedical areas including bioimaging, biodetection, and drug delivery. As an
      emerging field, DNA nanotechnology offers simple yet powerful design techniques
      for self-assembly of nanostructures with unique advantages and high potential in
      enhancing drug targeting and reducing drug toxicity. Various sequence programming
      and optimization approaches have been developed to design DNA nanostructures with
      precisely engineered, controllable size, shape, surface chemistry, and function.
      Potent anticancer drug molecules, including Doxorubicin and CpG oligonucleotides,
      have been successfully loaded on DNA nanostructures to increase their cell uptake
      efficiency. These advances have implicated the bright future of DNA
      nanotechnology-enabled nanomedicine. In this review, we begin with the origin of
      DNA nanotechnology, followed by summarizing state-of-the-art strategies for the
      construction of DNA nanostructures and drug payloads delivered by DNA
      nanovehicles. Further, we discuss the cellular fates of DNA nanostructures as
      well as challenges and opportunities for DNA nanostructure-based drug delivery.

PMID- 29465223
TI  - Magnetite and Green Rust: Synthesis, Properties, and Environmental Applications
      of Mixed-Valent Iron Minerals.
AB  - Mixed-valent iron [Fe(II)-Fe(III)] minerals such as magnetite and green rust have
      received a significant amount of attention over recent decades, especially in the
      environmental sciences. These mineral phases are intrinsic and essential parts of
      biogeochemical cycling of metals and organic carbon and play an important role
      regarding the mobility, toxicity, and redox transformation of organic and
      inorganic pollutants. The formation pathways, mineral properties, and
      applications of magnetite and green rust are currently active areas of research
      in geochemistry, environmental mineralogy, geomicrobiology, material sciences,
      environmental engineering, and environmental remediation. These aspects
      ultimately dictate the reactivity of magnetite and green rust in the environment,
      which has important consequences for the application of these mineral phases, for
      example in remediation strategies. In this review we discuss the properties,
      occurrence, formation by biotic as well as abiotic pathways, characterization
      techniques, and environmental applications of magnetite and green rust in the
      environment. The aim is to present a detailed overview of the key aspects related
      to these mineral phases which can be used as an important resource for
      researchers working in a diverse range of fields dealing with mixed-valent iron
      minerals.

PMID- 29465224
TI  - Uniform MnCo2O4 Porous Dumbbells for Lithium-Ion Batteries and Oxygen Evolution
      Reactions.
AB  - Three-dimensional (3D) binary oxides with hierarchical porous nanostructures are
      attracting increasing attentions as electrode materials in energy storage and
      conversion systems because of their structural superiority which not only create
      desired electronic and ion transport channels but also possess better structural
      mechanical stability. Herein, unusual 3D hierarchical MnCo2O4 porous dumbbells
      have been synthesized by a facile solvothermal method combined with a following
      heat treatment in air. The as-obtained MnCo2O4 dumbbells are composed of tightly
      stacked nanorods and show a large specific surface area of 41.30 m2 g-1 with a
      pore size distribution of 2-10 nm. As an anode material for lithium-ion batteries
      (LIBs), the MnCo2O4 dumbbell electrode exhibits high reversible capacity and good
      rate capability, where a stable reversible capacity of 955 mA h g-1 can be
      maintained after 180 cycles at 200 mA g-1. Even at a high current density of 2000
      mA g-1, the electrode can still deliver a specific capacity of 423.3 mA h g-1,
      demonstrating superior electrochemical properties for LIBs. In addition, the
      obtained 3D hierarchical MnCo2O4 porous dumbbells also display good oxygen
      evolution reaction activity with an overpotential of 426 mV at a current density
      of 10 mA cm-2 and a Tafel slope of 93 mV dec-1.

PMID- 29465225
TI  - Mechanochemical Regulated Origami with Tough Hydrogels by Ion Transfer Printing.
AB  - Stimuli-responsive hydrogels that undergo programmable shape deformation are of
      great importance for a wide variety of applications spanning from soft robotics
      and biomedical devices to tissue engineering and drug delivery. To guide shape
      morphing, anisotropic elements need to be encoded into the hydrogels during
      fabrication, which are extremely difficult to alter afterward. This study reports
      a simple and reliable mechanochemical regulation strategy to postengineer the
      hydrogels by encoding structures of high stiffness locally into prestretched
      tough hydrogels through ion transfer printing with a paper-cut. During printing,
      trivalent ions (Fe3+) were patterned and diffused into the prestretched tough
      gels, which dramatically increased the local stiffness by forming the second
      trivalent ionically cross-linked network. By removing the applied stretching
      force, the stiff anisotropy-encoded prestretched tough hydrogels underwent
      programmable shape morphing into complex three-dimensional origami structures due
      to the stiffness mismatch.

PMID- 29465226
TI  - Data-Independent Acquisition Coupled to Visible Laser-Induced Dissociation at 473
      nm (DIA-LID) for Peptide-Centric Specific Analysis of Cysteine-Containing Peptide
      Subset.
AB  - Thanks to comprehensive and unbiased sampling of all precursor ions, the interest
      to move toward bottom-up proteomic with data-independent acquisition (DIA) is
      continuously growing. DIA offers precision and reproducibility performances
      comparable to true targeted methods but has the advantage of enabling
      retrospective data testing with the hypothetical presence of new proteins of
      interest. Nonetheless, the chimeric nature of DIA MS/MS spectra inherent to
      concomitant transmission of a multiplicity of precursor ions makes the confident
      identification of peptides often challenging, even with spectral library-based
      extraction strategy. The introduction of specificity at the fragmentation step
      upon ultraviolet or visible laser-induced dissociation (LID) range targeting only
      the subset of cysteine-containing peptides (Cys-peptide) has been proposed as an
      option to streamline and reduce the search space. Here, we describe the first
      coupling between DIA and visible LID at 473 nm to test for the presence of Cys
      peptides with a peptide-centric approach. As a test run, a spectral library was
      built for a pool of Cys-synthetic peptides used as surrogates of human kinases (1
      peptide per protein). By extracting ion chromatograms of query standard and
      kinase peptides spiked at different concentration levels in an Escherichia coli
      proteome lysate, DIA-LID demonstrates a dynamic range of detection of at least 3
      decades and coefficients of precision better than 20%. Finally, the spectral
      library was used to search for endogenous kinases in human cellular extract.

PMID- 29465228
TI  - Interactions of 15N-Sulfadiazine and Soil Components As Evidenced by 15N-CPMAS
      NMR.
AB  - The extensive use of sulfonamides (SNs) in animal husbandry has led to an
      unintentional widespread occurrence in several environmental compartments. The
      implementation of regulations and management recommendations to reduce the
      potential risk of development of antibiotic resistances necessitates detailed
      knowledge on their fate in soil. We present results from two independent
      incubation studies of 15N-labeled sulfadiazines (SDZ) which focused on
      identifying binding types in bound residues. In the first study 15N-amino labeled
      SDZ was incubated with two previously isolated humic acids in the presence and
      absence of Trametes versicolor laccase, while in the second study 15N-double
      labeled SDZ was incubated with a typical agricultural Luvisol and the humic acid
      fraction isolated after sequential extraction of the soil. The freeze-dried humic
      acid fractions of both studies were then analyzed by 15N-CPMAS NMR and compared
      with the 15N-spectra of synthesized model compounds. In both studies amide bonds
      and Michael adducts were identified, while formation of imine bonds could be
      excluded. In the humic acid study, where less harsh extraction methods were
      applied, possible formation of H-bridging and sequestration were additionally
      detected.

PMID- 29465229
TI  - Sequential Protein Expression and Capsid Assembly in Cell: Toward the Study of
      Multiprotein Viral Capsids Using Solid-State Nuclear Magnetic Resonance
      Techniques.
AB  - While solid-state nuclear magnetic resonance (ssNMR) has emerged as a powerful
      technique for studying viral capsids, current studies are limited to capsids
      formed from single proteins or single polyproteins. The ability to selectively
      label individual protein components within multiprotein viral capsids and the
      resulting spectral simplification will facilitate the extension of ssNMR
      techniques to complex viruses. In vitro capsid assembly by combining individually
      purified, labeled, and unlabeled components in NMR quantities is not a viable
      option for most viruses. To overcome this barrier, we present a method that
      utilizes sequential protein expression and in cell assembly of component
      specifically labeled viral capsids in amounts suitable for NMR studies. We apply
      this approach to purify capsids of bacteriophage phi6 isotopically labeled on
      only one of its four constituent protein components, the NTPase P4. Using P4
      labeled phi6 capsids and the sensitivity enhancement provided by dynamic nuclear
      polarization, we illustrate the utility of this method to enable ssNMR studies of
      complex viruses.

PMID- 29465230
TI  - Aptamer-Patterned Hydrogel Films for Spatiotemporally Programmable Capture and
      Release of Multiple Proteins.
AB  - Various hydrogels have been used for protein delivery in the treatment of human
      diseases. Nevertheless, it is always difficult to control the capture and release
      of multiple proteins in different regions and periods. This research successfully
      proves that multiple proteins can be captured and released from the aptamer
      patterned hydrogel films with an adjustable release rate at a prospective time
      and in specific regions utilizing the complementary DNA strand of aptamers via
      photoclick chemistry and DNA hybridization. The hydrogel film is successfully
      applied to complex matrixes such as human serum and has excellent
      cytocompatibility. Thus, the aptamer-patterned hydrogel film will be a good
      candidate for controlled delivery of multiple proteins.

PMID- 29465231
TI  - Ab Initio Nonadiabatic Quantum Molecular Dynamics.
AB  - The Born-Oppenheimer approximation underlies much of chemical simulation and
      provides the framework defining the potential energy surfaces that are used for
      much of our pictorial understanding of chemical phenomena. However, this
      approximation breaks down when the dynamics of molecules in excited electronic
      states are considered. Describing dynamics when the Born-Oppenheimer
      approximation breaks down requires a quantum mechanical description of the
      nuclei. Chemical reaction dynamics on excited electronic states is critical for
      many applications in renewable energy, chemical synthesis, and bioimaging.
      Furthermore, it is necessary in order to connect with many ultrafast pump-probe
      spectroscopic experiments. In this review, we provide an overview of methods that
      can describe nonadiabatic dynamics, with emphasis on those that are able to
      simultaneously address the quantum mechanics of both electrons and nuclei. Such
      ab initio quantum molecular dynamics methods solve the electronic Schrodinger
      equation alongside the nuclear dynamics and thereby avoid the need for
      precalculation of potential energy surfaces and nonadiabatic coupling matrix
      elements. Two main families of methods are commonly employed to simulate
      nonadiabatic dynamics in molecules: full quantum dynamics, such as the
      multiconfigurational time-dependent Hartree method, and classical trajectory
      based approaches, such as trajectory surface hopping. In this review, we describe
      a third class of methods that is intermediate between the two: Gaussian basis set
      expansions built around trajectories.

PMID- 29465227
TI  - Synthesis and Applications of Perfunctionalized Boron Clusters.
AB  - This Viewpoint describes major advances pertaining to perfunctionalized boron
      clusters in synthesis and their respective applications. The first portion of
      this work highlights key synthetic methods, allowing one to access a wide range
      of polyhedral boranes (B4 and B6-B12 cluster cores) that contain exhaustively
      functionalized vertices. The second portion of this Viewpoint showcases the
      historical developments in using these molecules for applications ranging from
      materials science to medicine. Last, we suggest potential new directions for
      these clusters as they apply to both synthetic methods and applications.

PMID- 29465232
TI  - Exciton-Plasmon Interaction between AuNPs/Graphene Nanohybrids and CdS Quantum
      Dots/TiO2 for Photoelectrochemical Aptasensing of Prostate-Specific Antigen.
AB  - A competitive-displacement reaction strategy based on target-induced dissociation
      of gold nanoparticle coated graphene nanosheet (AuNPs/GN) from CdS quantum dot
      functionalized mesoporous titanium dioxide (CdS QDs/TiO2) was designed for the
      sensitive photoelectrochemical (PEC) aptasensing of prostate-specific antigen
      (PSA) through the exciton-plasmon interaction (EPI) between CdS QDs and AuNPs. To
      construct such an aptasensing system, capture DNA was initially conjugated
      covalently onto CdS QDs/TiO2-modified electrode, and then AuNPs/GN-labeled PSA
      aptamer was bound onto biofunctionalized CdS QDs/TiO2 via hybridization chain
      reaction of partial bases with capture DNA. Introduction of AuNPs/GN efficiently
      quenched the photocurrent of CdS QDs/TiO2 thanks to energy transfer. Upon
      addition of target PSA, the sandwiched aptamer between CdS QDs/TiO2 and AuNPs/GN
      reacted with the analyte analyte, thus resulting in the dissociation of AuNPs/GN
      from the CdS QDs/TiO2 to increase the photocurrent. Under optimum conditions, the
      aptasensing platform exhibited a high sensitivity for PSA detection within a
      dynamic linear range of 1.0 pg/mL to 8.0 ng/mL at a low limitat of detection of
      0.52 pg/mL. The interparticle distance of exciton-plasmon interaction and
      contents of AuNPs corresponding to EPI effect in this system were also studied.
      Good selectivity and high reproducibility were obtained for the analysis of
      target PSA. Importantly, the accuracy and matrix effect of PEC aptasensor was
      evaluated for the determination of human serum specimens and newborn calf serum
      diluted PSA standards, giving a well-matched result with the referenced PSA ELISA
      kit.

PMID- 29465233
TI  - Forward Osmosis Membranes under Null-Pressure Condition: Do Hydraulic and Osmotic
      Pressures Have Identical Nature?
AB  - Forward osmosis (FO) membranes fall into the category of nonporous membranes,
      based on the assumption that water and solute transport occur solely based on
      diffusion. The solution-diffusion (S-D) model has been widely used in predicting
      their performances in the coexistence of hydraulic and osmotic driving forces, a
      model that postulates the hydraulic and osmotic driving forces have identical
      nature. It was suggested, however, such membranes may have pores and mass
      transport could occur both by convection (i.e., volumetric flow) as well as by
      diffusion assuming that the dense active layer of the membranes is composed of a
      nonporous structure with defects which induce volumetric flow through the
      membranes. In addition, the positron annihilation technique has revealed that the
      active layers can involve relatively uniform porous structures. As such, the
      assumption of a nonporous active layer in association with hydraulic pressure is
      questionable. To validate this assumption, we have tested FO membranes under the
      conditions where hydraulic and osmotic pressures are equivalent yet in opposite
      directions for water transport, namely the null-pressure condition. We have also
      established a practically valid characterization method which quantifies the
      vulnerability of the FO membranes to hydraulic pressure.

PMID- 29465234
TI  - Multifunctional Compound Combining Conductivity and Single-Molecule Magnetism in
      the Same Temperature Range.
AB  - We report the first highly conducting single-molecule magnet, (BEDO)4[ReF6].6H2O
      [1; BEDO = bis(ethylenedioxo)tetrathiafulvalene], whose conductivity and single
      molecule magnetism coexist in the same temperature range. The compound was
      synthesized by BEDO electrocrystallization in the presence of (Ph4P)2[ReF6].2H2O
      and characterized by crystallography and measurements of the conductivity and
      alternating-current magnetic susceptibility.

PMID- 29465235
TI  - Postsynthetic Addition of Ligand Struts in Metal-Organic Frameworks: Effect of
      Syn/Anti Addition on Framework Structures with Distinct Topologies.
AB  - For the parent metal-organic framework (MOF) of UiO-type 1, postsynthetic
      bromination (anti addition) was readily carried out on the stilbene-ligand struts
      by directly adding excess bromine, whereas successful hydrogenation (syn
      addition) can only be achieved by slowing the reaction rate; otherwise, the
      crystalline structure of 1 will be irreversibly damaged. Meanwhile, Kagome-like
      MOF 2 can be smoothly modified by both postsynthetic bromination and
      hydrogenation. This study of the structural conversion not only represents the
      first example that adopts postsynthetic hydrogenation for modifying MOFs but also
      reveals various factors such as the reaction manner of syn/anti, framework
      topology, and reaction rate that can influence postsynthetic modification on the
      ligand struts of MOFs.

PMID- 29465236
TI  - Exploring Nuclear Photorelaxation of Pyranine in Aqueous Solution: an Integrated
      Ab-Initio Molecular Dynamics and Time Resolved Vibrational Analysis Approach.
AB  - Advances in time-resolved vibrational spectroscopy techniques provided a new
      stimulus for understanding the transient molecular dynamics triggered by the
      electronic excitation. The detailed interpretation of such time-dependent
      spectroscopic signals is a challenging task from both experimental and
      theoretical points of view. We simulated and analyzed the transient
      photorelaxation of the pyranine photoacid in aqueous solution, with special focus
      on structural parameters and low frequency skeleton modes that are possibly
      preparatory for the photoreaction occurring at later time, as suggested by
      experimental spectroscopic studies. To this aim, we adopted an accurate
      computational protocol that combines excited state ab initio molecular dynamics
      within an hybrid quantum mechanical/molecular mechanics framework and a time
      resolved vibrational analysis based on the Wavelet transform. According to our
      results, the main nuclear relaxation on the excited potential energy surface is
      completed in about 500 fs, in agreement with experimental data. The rearrangement
      of C-C bonds occurs according to a complex vibrational dynamics, showing
      oscillatory patterns that are out of phase and modulated by modes below 200 cm-1.
      We also analyzed in both the ground and the excited state the evolution of some
      structural parameters involved in excited state proton transfer reaction, namely,
      those involving the pyranine and the water molecule hydrogen bonded to the
      phenolic O-H group. Both the hydrogen bond distance and the intermolecular
      orientation are optimized in the excited state, resulting in a tighter proton
      donor-acceptor couple. Indeed, we found evidence that collective low frequency
      skeleton modes, such as the out of plane wagging at 108 cm-1 and the deformation
      at 280 cm-1, are photoactivated by the ultrafast part of the relaxation and
      modulate the pyranine-water molecule rearrangement, favoring the preparatory step
      for the photoreactivity.

PMID- 29465238
TI  - Orbital Symmetry and the Optical Response of Single-Layer MX Monochalcogenides.
AB  - We show that the absorption spectra of single-layer GaSe and GaTe in the
      hexagonal phase feature exciton peaks with distinct polarization selectivity. We
      investigate these distinct features from first-principles calculations using the
      GW-BSE formalism. We show that, because of the symmetry of the bands under in
      plane mirror symmetry, the bound exciton states selectively couple to either in
      plane or out-of-plane polarization of the light. In particular, for a p-polarized
      light absorption experiment, the absorption peaks of the hydrogenic s-like
      excitons emerge at large angle of incidence, while the overall absorbance reduces
      over the rest of the spectrum.

PMID- 29465237
TI  - Heterobimetallic [NiFe] Complexes Containing Mixed CO/CN- Ligands: Analogs of the
      Active Site of the [NiFe] Hydrogenases.
AB  - The development of synthetic analogs of the active sites of [NiFe] hydrogenases
      remains challenging, and, in spite of the number of complexes featuring a [NiFe]
      center, those featuring CO and CN- ligands at the Fe center are under
      represented. We report herein the synthesis of three bimetallic [NiFe] complexes
      [Ni( N2 S2)Fe(CO)2(CN)2], [Ni( S4)Fe(CO)2(CN)2], and [Ni( N2 S3)Fe(CO)2(CN)2]
      that each contain a Ni center that bridges through two thiolato S donors to a
      {Fe(CO)2(CN)2} unit. X-ray crystallographic studies on [Ni( N2 S3)Fe(CO)2(CN)2],
      supported by DFT calculations, are consistent with a solid-state structure
      containing distinct molecules in the singlet ( S = 0) and triplet ( S = 1)
      states. Each cluster exhibits irreversible reduction processes between -1.45 and 
      1.67 V vs Fc+/Fc and [Ni( N2 S3)Fe(CO)2(CN)2] possesses a reversible oxidation
      process at 0.17 V vs Fc+/Fc. Spectroelectrochemical infrared (IR) and electron
      paramagnetic resonance (EPR) studies, supported by density functional theory
      (DFT) calculations, are consistent with a NiIIIFeII formulation for [Ni( N2
      S3)Fe(CO)2(CN)2]+. The singly occupied molecular orbital (SOMO) in [Ni( N2
      S3)Fe(CO)2(CN)2]+ is based on Ni 3dz2 and 3p S with the S contributions deriving
      principally from the apical S-donor. The nature of the SOMO corresponds to that
      proposed for the Ni-C state of the [NiFe] hydrogenases for which a NiIIIFeII
      formulation has also been proposed. A comparison of the experimental structures,
      and the electrochemical and spectroscopic properties of [Ni( N2 S3)Fe(CO)2(CN)2]
      and its [Ni( N2 S3)] precursor, together with calculations on the oxidized [Ni(
      N2 S3)Fe(CO)2(CN)2]+ and [Ni( N2 S3)]+ forms suggests that the binding of the
      {Fe(CO)(CN)2} unit to the {Ni(CysS)4} center at the active site of the [NiFe]
      hydrogenases suppresses thiolate-based oxidative chemistry involving the bridging
      thiolate S donors. This is in addition to the role of the Fe center in modulating
      the redox potential and geometry and supporting a bridging hydride species
      between the Ni and Fe centers in the Ni-C state.

PMID- 29465239
TI  - Synthesis of Vicinal Dichlorides via Activation of Aliphatic Terminal Epoxides
      with Triphosgene and Pyridine.
AB  - Herein we report a novel synthetic reaction to convert unactivated terminal
      aliphatic epoxide to alkyl vicinal dichloride based on triphosgene-pyridine
      activation. Our methodology is operationally simple and readily tolerated by a
      broad of scope of substrates as well as protecting groups. Furthermore, these
      mild conditions generally yield clean reaction mixtures that are free of
      byproducts upon aqueous workup.

PMID- 29465240
TI  - Competitive Halogen Bond in the Molecular Ferroelectric with Large Piezoelectric
      Response.
AB  - Molecular piezoelectrics are attracting tremendous interest because of their easy
      processing, light weight, low acoustical impedance, and mechanical flexibility.
      However, reports of molecular piezoelectrics with a piezoelectric coefficient d33
      comparable to piezoceramics such as barium titanate (BTO, 90-190 pC/N) have been
      scarce. Here, we present a uniaxial molecular ferroelectric,
      trimethylchloromethylammonium tribromocadmium(II) (TMCM-CdBr3), in which the
      halogen bonding might be a possible critical point for the stabilization of one
      dimensional (1D) {CdBr3}- chain and further reservation of its ferroelectricity
      in such organic-inorganic hybrid crystalline systems. It has a large d33 of 139
      pC/N, 1 order of magnitude higher than those of most classically uniaxial
      ferroelectrics such as LiNbO3 (6-16 pC/N) and Rochelle salt (~7 pC/N), and
      comparable with those of multiaxial ferroelectrics such as BTO and
      trimethylbromomethylammonium tribromomanganese(II) (112 pC/N). Moreover, the
      simple single-crystal growth and easy-to-find polar axis enable it to hold a
      great potential for applying in the single-crystal form. In light of the strong,
      specific, and directional halogen-bonding interactions, this work provides
      possibilities to explore new classes of molecular piezoelectrics and contribute
      to further developments.

PMID- 29465241
TI  - Response of Membranes and Vesicles to Capillary Forces Arising from Aqueous Two
      Phase Systems and Water-in-Water Droplets.
AB  - Aqueous two-phase systems and water-in-water emulsions have attracted much recent
      interest. Here, we theoretically study the interactions of such systems with
      biomimetic membranes and giant unilamellar vesicles (GUVs). For partial wetting,
      the water-water interface and the membrane form a three-phase contact line that
      partitions the membrane into two distinct segments with different tensions and
      different curvature-elastic properties. On the nanometer scale, the capillary
      forces arising from the water-water interface lead to a smoothly curved membrane
      that forms an intrinsic contact angle with the interface. The corresponding
      balance conditions are derived here for general curvature-elastic parameters of
      the two membrane segments. On the micrometer scale, the capillary forces deform
      the membrane segments into spherical caps with an apparent kink along the contact
      line. A new computational method is introduced by which these piece-wise
      spherical vesicle shapes can be analyzed in a systematic manner. The method is
      based on a general relationship that is reminiscent of Neumann's triangle but
      depends explicitly on the curvatures of the membrane segments. For certain
      regions of the parameter space, corresponding to small or large spontaneous
      curvatures, the force balance along the apparent contact line can be described in
      a self-consistent manner and then leads to curvature-independent relationships
      that involve the total membrane tensions. The different relationships can be used
      to determine the material parameters of the droplet-vesicle system from the
      observed morphologies of the GUVs. The approach described here is quite general
      and can be applied to different membrane compositions and aqueous two-phase
      systems. The same computational approach can also be used to elucidate the
      response of biological membranes to the recently discovered membrane-less,
      droplet-like organelles.

PMID- 29465242
TI  - Emergence of Droplets at the Nonequilibrium All-Aqueous Interface in a Vertical
      Hele-Shaw Cell.
AB  - The interfacial phenomena at liquid-liquid interfaces remain the subject of
      constant fascination in science and technology. Here, we show that fingers
      forming at the interface of nonequilibrium all-aqueous systems can spontaneously
      break into an array of droplets. The dynamic formation of droplets at the water
      water (w/w) interface is observed when a less dense aqueous phase, for instance,
      the dextran solution, is placed on a denser aqueous phase, the polyethylene
      glycol solution, in a vertical Hele-Shaw cell. Because of the gradual diffusion
      of water from the upper phase into the lower phase, a dense layer appears at the
      nonequilibrium w/w interface. As a result, a periodic array of fingers emerge and
      sink. Remarkably, these fingers break up and an array of droplets are emitted
      from the interface. We characterize the wavelength of fingering by measuring the
      average distance between the dominant fingers. By varying the initial
      concentrations of the two nonequilibrium aqueous phases, we identify
      experimentally a phase diagram with a wide parameter space in which finger
      breaking occurs. Finally, plenty of droplets, spontaneously formed when one phase
      is continuously deposited onto another aqueous phase, further confirm the
      robustness of our experimental results. Our work suggests a simple yet efficient
      approach with a potential upscalability to generate all-aqueous droplets.

PMID- 29465243
TI  - Converging Energy Transfer in Polynuclear Ru(II) Multiterpyridine Complexes:
      Significant Enhancement of Luminescent Properties.
AB  - Ruthenium-based complexes are widely used as photocatalysts, as photosensitizers,
      or as building blocks for supramolecular assemblies. In the field of solar energy
      conversion, building light harvesting antenna is of prime interest. Nevertheless,
      collecting light is mandatory but not sufficient; once collected and transferred,
      the exciton has to be long-lived enough to be transferred to a catalytic site. If
      Ru(II) terpyridine complexes are prime building blocks for structural reasons,
      the short lifetime of their excited state prevents their use as a harvesting
      center in light antennae. In this paper, we present new polynuclear assemblies,
      based on Ru(II)-terpyridine units where delocalization of the excited state is
      combined with an antenna effect. As a consequence, complexes C1-C3 display long
      lived excited states compared to [Ru(tpy)2]2+, making them promising efficient
      antenna building blocks to be connected to a final acceptor or a catalytic
      center.

PMID- 29465244
TI  - Study of Meldrum's Acid Cyclization Reactions.
AB  - On the basis of the cyclization reactions reported by Danishefsky et al. of
      Meldrum's acid hydroxylethyl and anilinoethyl derivatives, the cyclization of the
      sulfamidomethylene and ureidomethylene derivatives was attempted without success.
      To understand the lack of reactivity of these compounds versus the successful
      cyclization of the ethyl derivatives, the corresponding mechanisms of reaction
      for both processes have been explored by means of MP2/6-311+G(d,p) calculations
      in an aqueous environment. The conformational analysis of all of these structures
      revealed that, while for the ethyl derivatives the minimum energy conformation
      corresponds to that of the cyclization initiating structure, for the methylene
      analogues the entrance channel conformations are substantially less stable than
      the energy minimum. Intramolecular hydrogen bonds were found in all of the energy
      minima as well as in the cyclization initiating conformations as determined by
      analysis of their electron density. The potential energy surfaces for the
      successful and unsuccessful cyclization processes were obtained at room
      temperature and 100  degrees C. Comparison of both processes allows
      rationalization that the lack of reactivity of the methylene derivatives can be
      thermodynamically explained based not only on the strength of the intramolecular
      hydrogen bond formed in their energy minima but also by the energy penalty needed
      to reach the entrance channel conformation and by the calculated energy barriers.

PMID- 29465245
TI  - Electronic Level Alignment at an Indium Tin Oxide/PbI2 Interface and Its
      Applications for Organic Electronic Devices.
AB  - The electronic level alignment at the indium tin oxide (ITO)/PbI2 interface is
      investigated by an ultraviolet photoelectron spectroscopy. An n-type conductivity
      property is found for PbI2 as well as a downward shift energy level at the
      ITO/PbI2 interface. These indicate that PbI2 can be used as an anode buffer layer
      for organic electronic devices. The power conversion efficiency of the organic
      solar cell based on tetraphenyldibenzoperiflanthene/C70 planar heterojunction is
      dramatically increased from 1.05 to 3.82%. Meanwhile, the thermally activated
      delayed fluorescence organic light-emitting diode based on 4,4',4"-tri( N
      carbazolyl)triphenylamine-((1,3,5-triazine-2,4,6-triyl)tris(benzene-3,1
      diyl))tris(diphenylphosphine oxide) shows a significantly reduced turn-on voltage
      and enhanced power efficiency from 6.26 to 18.60 lm/W. The improved performance
      is attributed to the high hole injection/extraction efficiency at the ITO/PbI2
      interface. Besides, the near-infrared (NIR) absorption of lead phthalocyanine
      (PbPc)-based NIR organic photodetector (NIR-OPD) is dramatically increased,
      indicating that the PbI2 layer can also be used as a template layer for the
      growth of the triclinic phase of PbPc. As a result, the optimized device shows an
      external quantum efficiency of 26.7% and a detectivity of 9.96 * 1011 jones at
      900 nm, which are among the highest ones reported for organic NIR-OPDs.

PMID- 29465246
TI  - Hybrid Dion-Jacobson 2D Lead Iodide Perovskites.
AB  - The three-dimensional hybrid organic-inorganic perovskites have shown huge
      potential for use in solar cells and other optoelectronic devices. Although these
      materials are under intense investigation, derivative materials with lower
      dimensionality are emerging, offering higher tunability of physical properties
      and new capabilities. Here, we present two new series of hybrid two-dimensional
      (2D) perovskites that adopt the Dion-Jacobson (DJ) structure type, which are the
      first complete homologous series reported in halide perovskite chemistry. Lead
      iodide DJ perovskites adopt a general formula A'A n-1Pb nI3 n+1 (A' = 3
      (aminomethyl)piperidinium (3AMP) or 4-(aminomethyl)piperidinium (4AMP), A =
      methylammonium (MA)). These materials have layered structures where the stacking
      of inorganic layers is unique as they lay exactly on top of another. With a
      slightly different position of the functional group in the templating cation 3AMP
      and 4AMP, the as-formed DJ perovskites show different optical properties, with
      the 3AMP series having smaller band gaps than the 4AMP series. Analysis on the
      crystal structures and density functional theory (DFT) calculations suggest that
      the origin of the systematic band gap shift is the strong but indirect influence
      of the organic cation on the inorganic framework. Fabrication of photovoltaic
      devices utilizing these materials as light absorbers reveals that
      (3AMP)(MA)3Pb4I13 has the best power conversion efficiency (PCE) of 7.32%, which
      is much higher than that of the corresponding (4AMP)(MA)3Pb4I13.

PMID- 29465247
TI  - Viability of single balloon enteroscopy performed under endoscopist-directed
      sedation.
AB  - INTRODUCTION: there is a lot of controversy with regard to who should be
      responsible for sedation during digestive endoscopy, particularly in advanced
      procedures that require deep sedation such as enteroscopy. The aim of this study
      was to evaluate the endoscopist-directed sedation viability during single balloon
      enteroscopy. MATERIAL AND METHOD: this was a prospective, observational study of
      a series of consecutive enteroscopies. The clinical staff included an
      endoscopist, scrub nurse and a nurse in charge of monitoring and sedative
      administration. The following parameters were monitored: pulse oximetry, blood
      pressure (every five minutes), electrocardiogram and respiratory rate. There was
      continuous supplemental oxygen and CO2 insufflation. The patient was in the left
      lateral decubitus position and a fluoroscopic control was used. RESULTS: forty
      four explorations were performed in 39 patients, 24 were male and 15 female. The
      median age was 74 (18-89) and the ASA score was I in 12 cases, II in 23 cases and
      III in nine cases. Comorbidities were present in 68% of cases. The drugs used
      included propofol in 23 cases, propofol and midazolam in ten cases,
      propofol/midazolam/fentanyl in two cases, propofol and fentanyl in two cases, and
      midazolam/fentanyl in seven cases. All procedures were complete. The length of
      the procedure was 52 minutes (20-120). There were diagnostic findings in 65.9% of
      cases and therapeutic measures in 47.7%. There were no severe complications and
      the rate of complications derived from sedation was 22.7%. CONCLUSION:
      endoscopist-directed sedation is effective and safe for single balloon
      enteroscopy. Multi-center and wider studies are needed in order to better assess
      the efficacy, safety and efficiency of sedation controlled by a non-anesthetist
      during advanced endoscopy in this field.

PMID- 29465248
TI  - Quality of sedation with propofol administered by non-anesthetists in a digestive
      endoscopy unit: the results of a one year experience.
AB  - INTRODUCTION: research has shown that an endoscopist-nurse clinical team can
      perform sedation with propofol effectively, safely and efficiently. To do so, it
      is essential to provide specific and appropriate training in the necessary
      skills. The main aim of the present study was to evaluate the quality of the
      sedation procedure administered by non-anesthetists in a digestive endoscopy
      unit, one year after its introduction. METHODS: a prospective cohort study was
      performed in patients given propofol sedation by non-anesthetists. Subsequently,
      a random sample of clinical records was selected in order to evaluate the
      adherence of professionals to the quality criteria and to assess the rate of
      adverse events related to sedation. RESULTS: a total of 595 procedures were
      performed under propofol sedation during the study period. The rate of adverse
      events was 2.4% (n = 507), mainly involving hypotension and hypoxemia. Adherence
      to the sedation procedure was above 80% for most of the applicable criteria,
      although it was lower for the completion of ASA risk evaluation. CONCLUSIONS: the
      results of the study suggest that propofol can be administered safely and
      effectively by a qualified endoscopist-nurse team, in patients with an ASA I-II
      risk. Audits of adherence by medical staff to the recommended procedure
      facilitate the identification of areas for improvement; further work is needed on
      the aspects that have not yet been consolidated.

PMID- 29465249
TI  - The right colon challenge.
AB  - Colorectal cancer (CRC) is the third most common cancer and the fourth cause of
      cancer-related mortality worldwide. In an attempt to raise awareness on this
      situation, and to implement preventive measures, March 31st has been established
      as international colorectal cancer awareness day. Our country, with the Spanish
      "Alianza para la Prevencion del Cancer de Colon", pioneered in 2008 an
      institution that brought together scientific and civil societies to pursue this
      goal. A stabilization, even a decrease in the incidence and mortality of this
      condition has been reported in western countries for the last few years, which
      may be attributed to a number of highly relevant factors.

PMID- 29465250
TI  - Continuous esomeprazole infusion versus bolus administration and second look
      endoscopy for the prevention of rebleeding in children with a peptic ulcer.
AB  - INTRODUCTION: the majority of studies of acute gastrointestinal bleeding in
      children are retrospective, focusing on therapeutic endoscopy. Previous studies
      performed in adult patients have demonstrated that both scheduled second look
      endoscopy and high dose continuous omeprazole infusion are effective in the
      prevention of peptic ulcer rebleeding. The aim of this study was to compare the
      efficacy of these two strategies using esomeprazole for the prevention of
      rebleeding following primary endoscopic hemostasis in children with peptic
      ulcers. The main outcome was to assess the rebleeding rate within 30 days after
      the initial hemostasis. METHODS: consecutive pediatric cases who underwent
      endoscopic treatment for bleeding peptic ulcers were randomized into two
      treatment groups following hemostasis. The first group received esomeprazole as
      an intravenous bolus every 12 hours for 72 hours and a routine second look
      endoscopy within 12-24 hours with endotherapy retreatment in the case of a
      persistent stigmata of bleeding. The second group received a continuous high dose
      esomeprazole infusion for 72 hours without endoscopic reassessment unless
      required due to rebleeding. RESULTS: a total of 63 children were randomized to
      the second look endoscopy group and 64 to the esomeprazole infusion group.
      Rebleeding occurred within 30 days in four patients (6.3%) in the first group and
      in three patients (4.6%) in the second group (p = 0.7). CONCLUSIONS: a
      pharmaceutical approach using a high dose continuous esomeprazole infusion in
      children after an initial endoscopic hemostasis has a similar efficacy compared
      to second look endoscopy and bolus esomeprazole administration for the prevention
      of peptic ulcer rebleeding. Thus, the discomfort of a second endoscopy in
      children can be avoided and is only recommended for selected high risk cases.

PMID- 29465251
TI  - Managing iron deficiency and iron deficiency anemia in inflammatory bowel
      disease. The results of the "Gestiona hierro-EII" survey.
AB  - INTRODUCTION: iron deficiency anemia is a common and very relevant manifestation
      of inflammatory bowel disease (IBD). Although clinical practice guidelines have
      been published and updated on this subject, the management in the daily practice
      of this complication is far from optimal. OBJECTIVE: to determine the actual
      management, needs and limitations of anemia in IBD by means of a survey of
      gastroenterology specialists. MATERIAL AND METHODS: a self-administered telematic
      survey was carried out between April and May 2017 and was sent to SEPD members.
      The survey included four sections: participant demographics, monitoring,
      treatment and limitations/needs. RESULTS: a total of 122 evaluable surveys were
      received from all Spanish autonomous communities. Iron deficiency anemia is
      considered as a frequent manifestation of IBD and is monitored in all patients
      via the measurement of hemoglobin and ferritin. In the case of anemia, the survey
      respondents found it necessary to rule out the presence of IBD activity. However,
      only 14.8% prescribed intravenous iron when IBD was active. The required dose of
      intravenous iron is mainly calculated according to patient needs but only 33.1%
      of clinicians infused doses of 1 g or more. CONCLUSIONS: the "Gestiona Hierro
      EII" survey on the management of anemia in IBD demonstrated a high quality of
      care, even though some aspects need to be improved. These included the
      prescription of intravenous iron for patients with disease activity, the use of
      high-dose intravenous iron and the implementation of algorithms into clinical
      practice.

PMID- 29465252
TI  - Increasing uptake of comparative effectiveness and patient-centered outcomes
      research among stakeholders: insights from conference discussion.
AB  - The goal of comparative effectiveness research (CER) and patient-centered
      outcomes research (PCOR) is to improve health outcomes by providing stakeholders
      with evidence directly relevant to decision making. In January 2017, the
      Pharmaceutical Research and Manufacturers Association Foundation, alongside the
      Academy for Managed Care Pharmacy, organized a conference aimed at engaging
      experts and opinion leaders representing clinicians, patients and payers to
      identify and discuss barriers and strategies to enhancing uptake and use of
      CER/PCOR. This report summarizes the conference discussion in the following
      sections: preconference survey; summary of barriers and strategies to the uptake
      of CER/PCOR identified by conference attendees; and future perspectives on the
      field.

PMID- 29465253
TI  - Nanocrystal: a novel approach to overcome skin barriers for improved topical drug
      delivery.
AB  - INTRODUCTION: Skin is an important route of drug delivery for the treatment of
      various dermatological conditions. The advent of nanotechnology is paving the
      roadmaps for topical drug delivery by providing sustained release as well as
      maintaining a localized effect, outweighing the toxicity concern. Area covered:
      This review highlighted the morphology of skin, its barrier nature as well as
      drug penetration pathways after topical application of formulations. The existing
      methods to improve topical drug delivery, by infringing or permeating the skin
      barriers, are discussed. This context concretes the foundation to accentuate the
      need for the development of nanocrystal-based topical formulation. The mechanism
      of drug release, immediate as well as sustained release, after topical
      administration of drug nanocrystals is also elaborated. The special emphasis is
      given on the breakthrough achieved, in topical drug delivery using drug
      nanocrystals, so far in the plethora of literature, patents, and products, under
      clinical trial as well as in the market. Expert opinion: The current research on
      nanocrystals for topical drug delivery is highlighting the breakthroughs achieved
      so far. The output of these research envisages that topical nanocrystals based
      formulations can be a novel strategy for the drugs which are facing solubility,
      bioavailability and toxicity concerns.

PMID- 29465254
TI  - Type and doses of oral anticoagulants and adherence to anticoagulant treatment in
      elderly patients with atrial fibrillation: the ESPARTA study.
AB  - AIM: To analyze the use of oral anticoagulants in elderly patients with atrial
      fibrillation in clinical practice. PATIENTS & METHODS: Cross-sectional and
      multicenter study performed in atrial fibrillation patients >=75 years treated
      with oral anticoagulants >=3 months. RESULTS: 837 patients (83.0 +/- 5.0 years;
      CHA2DS2-VASc 5.0 +/- 1.4; HAS-BLED 2.1 +/- 0.9; 70.8% vitamin K antagonists;
      29.2% direct oral anticoagulants [DOACs]) were included. Poor adherence was
      observed in 27.9% of patients. Higher scores in the Pfeiffer's test and FRAIL
      scale were associated with poorer adherence. Among patients treated with DOACs,
      62.3% received the lower doses. Having high CHADS2 score and being older were
      associated with the use of low doses. CONCLUSION: 28% of patients had a poor
      adherence to anticoagulant treatment. 62% of patients were treated with the lower
      doses of DOACs.

PMID- 29465255
TI  - "You have Endometriosis": Making Menstruation-Related Pain Legitimate in a
      Biomedical World.
AB  - In this essay, the author reflects on how biomedical and gendered perceptions of
      reproductive health can impact an illness experience. Using a narrative lens, she
      relays the frustration of attempting to have her excessive menstrual pain
      legitimated and treated when loved ones and medical professionals trivialized it
      and refused to let her take on the sick role. She recounts incidents that
      demonstrate the embedded and limiting persistence of gendered perceptions of
      pain. In the end, she argues that only through strong patient self-advocacy and
      knowledge can one rewrite the social scripts assigned to how women cope with
      menstrual pain.

PMID- 29465256
TI  - Managing Anti-Fat Stigma in Primary Care: An Observational Study.
AB  - : In many wealthy countries, fatness is stigmatized as a sign of personal
      failure. Health care interactions can enact fat-related stigmatization, which can
      worsen health outcomes. The present analysis highlights how stigmatizing
      discourses about fat bodies emerge in primary care appointments, and examines
      immediate conversational effects. METHODS: Observational study in three primary
      care clinics in Canada, using conversation and discourse analytic methods on
      transcripts of 29 audio-recorded appointments with adults. Talk about weight and
      blood pressure are contrasted. RESULTS: During measurement and review of
      measurements, clinicians routinely interpreted the blood pressure result but
      rarely interpreted weight. Patients of varied ages and body sizes often filled
      the interpretative vacuum, and focused on behaviors. Overall, neither patients
      nor clinicians challenged the stigmatizing discourses associated with fat bodies,
      but sometimes agreed that the "personal failure" frame associated with fatness
      does not apply to the particular patient. Physicians rarely raised other
      determinants of weight, but often did so when talking about blood pressure.
      CONCLUSIONS: Across most body types and ages, weight-related talk spurred stigma
      management from adult patients. Patients' interpretations were consistent with
      accepting or avoidant strategies to manage stigma. The findings challenge
      clinicians and researchers to frame patients' defensiveness or sensitivity as a
      predictable response to mitigate stigma, and consider how clinical care might be
      better structured to avoid stigmatization. Recognizing the range of determinants
      of weight with interpretation of weight may help, particularly if combined with
      other methods to de-stigmatize care. The results have implications for clinical
      weight management and behavior change support.

PMID- 29465257
TI  - Investigational drugs in development to prevent neuromyelitis optica relapses.
AB  - INTRODUCTION: In the short time since 2014, three pivotal, worldwide studies in
      neuromyelitis optica spectrum disorders have been launched: eculizumab, SA237 and
      inebelizumab, each based on a unique mechanism. Areas covered: In this review, we
      provide a discussion on the trial data available for each drug, a brief
      description of the trial design, and our expert opinion on the potential benefits
      and risks. Expert opinion: Eculizumab, a C5 complement inhibitor, may prove
      useful in the treatment of intractable cases of NMOSD, but physicians must be
      aware of the known risk of meningococcal infection. SA237, an interleukin-6
      receptor blocker, may be effective at reducing relapse risk, and also has the
      potential to reduce neuropathic pain in NMOSD. Inebelizumab, a B cell depleting
      agent, has never been tested in NMOSD, but based on extensive evidence of
      efficacy with B cell depletion using rituximab, inebelizumab is expected to work
      at least as well.

PMID- 29465258
TI  - Administration of low-molecular-weight heparin in patients with two or more
      unsuccessful IVF/ICSI cycles: a multicenter cohort study.
AB  - To compare the effects of the administration of low-molecular-weight heparin
      (LMWH) in subfertile patients with two or more unsuccessful IVF/ICSI cycles. In
      this six-center two-arm retrospective cohort study, the study population (230
      women) underwent a GnRH-antagonist protocol and was classified into two groups,
      according to the couse of LMWH or not. Groups were compared regarding the
      clinical and IVF/ICSI cycle characteristics and reproductive outcomes, whereas
      clinical pregnancy and miscarriage constituted the primary endpoints. Logistic
      regression analysis was performed to determine the potential predictors of
      clinical pregnancy, miscarriage and live birth rates using the Enter method.
      Baseline characteristics were comparable in the two groups. There was no
      statistically significant difference between the two study groups with regard
      neither to clinical pregnancy and miscarriage rates (33/133 vs. 20/97, p = .456
      and 15/133 vs. 9/97, p = .624, respectively), nor to the secondary outcomes
      preset for this study (all p values >.05). Logistic regression revealed that age
      of the woman and ICSI and dose of gonadotrophins used were predictors of clinical
      pregnancy and live birth, respectively. In conclusion, there is no evidence to
      support the standard addition of LMWH in patients with two or more unsuccessful
      IVF/ICSI cycles.

PMID- 29465259
TI  - Latent tuberculosis in childhood: tolerability of two different therapeutic
      approaches.
AB  - BACKGROUND: Isoniazid monotherapy for six or nine months and the combination of
      isoniazid and rifampicin for three or four months are the most used regimens for
      treating latent tuberculosis. The main aim of this retrospective study is to
      evaluate the safety of latent tuberculosis treatment by analysing side effects in
      both regimens. RESEARCH DESIGN AND METHODS: Children with latent tuberculosis and
      treated with isoniazid or isoniazid and rifampicin were included. Periodic
      evaluations with clinical assessment and blood exams were carried out to detect
      any adverse reaction, including elevated serum transaminases. RESULTS: 441
      children were included, 14.5% treated with isoniazid and 85.5% with isoniazid and
      rifampicin. Five patients under combined treatment developed hepatotoxicity
      within the first month. None of the patients under isoniazid monotherapy
      presented hepatotoxicity. A slight increase of transaminases level was found in
      both groups (18.7% in isoniazid and 10.3% in isoniazid/rifampicin groups,
      respectively) without causing discontinuation of treatment, with values
      normalization at the subsequent checks. CONCLUSIONS: Both regimens resulted safe.
      Hepatotoxicity occurred rarely and within the first month. For this reason, it
      may be appropriate to perform liver function tests after about one month from the
      beginning of therapy to avoid diagnostic delays.

PMID- 29465260
TI  - The effect of Knee-Ankle-Foot orthosis stiffness on the parameters of walking.
AB  - The purpose of this simulation study was to analyze the effect of variation in
      Knee-Ankle-Foot-Orthosis stiffness on the joint power and the energy cost of
      walking. The effect of contractile tissue was simulated using linear elastic
      spring and viscous dampers in knee and ankle joints. Then, joint angles, ground
      reaction force, were collected from Twenty chronic hemiparesis subjects (15 males
      and 5 females) and twenty control subjects (14 males and 6 females), and spring
      stiffness were considered as the inputs. In this new study, the generated muscle
      torques were optimized by changing the stiffness as the desired output in the
      mathematical model attained by the MATLAB SimMechanics toolbox. Finally, the
      simulated mathematical model was introduced as an appropriate substitute in
      obtaining the optimized stiffness with a more convenient and efficient designed
      orthosis.

PMID- 29465261
TI  - Lipid Synthesis Is Required to Resolve Endoplasmic Reticulum Stress and Limit
      Fibrotic Responses in the Lung.
AB  - Endoplasmic reticulum (ER) stress is evident in the alveolar epithelium of humans
      and mice with pulmonary fibrosis, but neither the mechanisms causing ER stress
      nor the contribution of ER stress to fibrosis is understood. A well-recognized
      adaptive response to ER stress is that affected cells induce lipid synthesis;
      however, we recently reported that lipid synthesis was downregulated in the
      alveolar epithelium in pulmonary fibrosis. In the present study, we sought to
      determine whether lipid synthesis is needed to resolve ER stress and limit
      fibrotic remodeling in the lung. Pharmacologic and genetic manipulations were
      performed to assess whether lipid production is required for resolving ER stress
      and limiting fibrotic responses in cultured alveolar epithelial cells and whole
      lung tissues. Concentrations of ER stress markers and lipid synthesis enzymes
      were also measured in control and idiopathic pulmonary fibrosis lung tissues. We
      found that chemical agents that induce ER stress (tunicamycin or thapsigargin)
      enhanced lipid production in cultured alveolar epithelial cells and in the mouse
      lung. Moreover, lipid production was found to be dependent on the enzyme stearoyl
      coenzyme A desaturase 1, and when pharmacologically inhibited, ER stress
      persisted and lung fibrosis ensued. Conversely, lipid production was reduced in
      mouse and human fibrotic lung, despite there being an increase in the magnitude
      of ER stress. Furthermore, augmenting lipid production effectively reduced ER
      stress and mitigated fibrotic remodeling in the mouse lung after exposure to
      silica. Augmenting lipid production reduces ER stress and attenuates fibrotic
      remodeling in the mouse lung, suggesting that similar approaches might be
      effective for treating human fibrotic lung diseases.

PMID- 29465262
TI  - Glecaprevir + pibrentasvir for treatment of hepatitis C.
AB  - INTRODUCTION: Glecaprevir/pibrentasvir is a fixed-dose combination regimen of a
      new generation NS3/4A inhibitor and an NS5A inhibitor with potent antiviral
      activity against all hepatitis C virus (HCV) genotypes. This regimen offers a
      shorter course of therapy (8 weeks) for selected patients regardless of genotype
      and has demonstrated high virological efficacy for retreatment of individuals who
      previously failed an NS5A containing regimen. Glecaprevir and pibrentasvir are
      minimally excreted by the kidneys; thus this regimen can safely be used in
      individuals with severe chronic kidney disease (CKD), including those undergoing
      hemodialysis. Areas covered: This review covers the mechanism of action,
      pharmacokinetics, clinical applications, efficacy, and safety profile of
      glecaprevir/pibrentasvir. It also covers key phase 2 and 3 clinical trials that
      led to licensure of this regimen. Expert opinion: Glecaprevir/pibrentasvir is the
      latest antiviral regimen licensed in the United States for treatment of HCV
      infection. Although several other direct-acting antiviral agents (DAAs) are
      currently available, glecaprevir/pibrentasvir has some unique characteristics
      that expand treatment options for HCV infection, including patients with
      comorbidities such as advanced stage CKD or prior treatment failure to antiviral
      regimens containing other DAAs.

PMID- 29465263
TI  - Experience with developing antibiotic stewardship programs in Serbia: potential
      model for other Balkan countries?
AB  - AIM: Antimicrobial resistance and inappropriate use of antibiotics in children
      are important issues. Consequently, there is a need to develop comprehensive
      stewardship programs even in hospitals with limited resources starting with
      children's hospitals. METHODS: Retrospective observational analysis of
      antimicrobial utilization and resistance patterns over 5 years in a tertiary care
      children's hospital in Serbia. RESULTS: Cumulative antimicrobial resistance
      decreased but was still high, with high cumulative resistance rates among the
      most widely used antibiotics in the hospital. Total antibiotic use decreased from
      2010 to 2014 although there was still high prescribing of reserved antibiotics.
      CONCLUSION: Concerns with inappropriate use and high resistance rates among some
      antibiotics used in the hospital are being used to develop guidance on future
      antibiotic use in this hospital, building on the recently introduced antibiotic
      stewardship program, as well as encourage other hospitals in Serbia to review
      their policies.

PMID- 29465265
TI  - Validation of the DSM-5 Alternative Model Personality Disorder Diagnoses in
      Turkey, Part 1: LEAD Validity and Reliability of the Personality Functioning
      Ratings.
AB  - This study addresses longitudinal, expert, all data (LEAD) validity and
      reliability of the personality functioning ratings in Turkey, which are essential
      in assessing Criterion A for the entire DSM-5 alternative model for personality
      disorders (AMPD) diagnoses. A total of 120 consenting patients recruited at a
      university psychiatry clinic were rated by individual clinicians with respect to
      DSM-III-R and AMPD criteria. Subsequently, a LEAD panel consisting of 3 senior
      clinicians convened to reach a consensus personality disorder diagnosis for each
      participant. Blind personality functioning ratings of a subgroup of 20
      participants by the same set of 4 clinicians were obtained for test-retest
      reliability investigation. Concordance between the LEAD and AMPD diagnoses was as
      good as that between the LEAD and DSM-III-R diagnoses (kappas = .68). The
      personality functioning scores correlated strongly (r > .50) with the sum of
      specific DSM-III-R diagnoses. Reliability estimates pertaining to the personality
      functioning scores and resultant AMPD Criterion A decisions were mostly in the
      good range. In conclusion, DSM-5 alternative model-oriented personality
      functioning ratings yield total or composite scores that are evidently valid and
      reliable tools to diagnose general personality disorder and to estimate its
      global severity.

PMID- 29465264
TI  - Ibrutinib inhibits free fatty acid metabolism in chronic lymphocytic leukemia.
AB  - Unlike normal B-cells, and similar to fat cells, chronic lymphocytic leukemia
      (CLL) cells aberrantly express lipoprotein lipase (LPL), which contributes to
      free fatty acids (FFAs) metabolism. Here we show that, in CLL cells, the B-cell
      receptor (BCR) inhibitor ibrutinib reduced LPL mRNA and protein levels and
      inhibited FFA metabolism in vitro. Likewise, in CLL cells from ibrutinib-treated
      patients, FFA metabolism was reduced and eventually stopped. Because ibrutinib
      disrupts CLL cells' ability to use FFAs for energy production, and because
      various BCR-dependent cellular functions rely on a continuous supply of chemical
      energy, ibrutinib interrupts several pathways imperative for cellular function in
      CLL cells.

PMID- 29465266
TI  - Cardiotoxicity associated with carfilzomib: systematic review and meta-analysis.
AB  - Carfilzomib is a second-generation proteasome inhibitor (PI) that is approved for
      patients with relapsed or refractory multiple myeloma (RRMM) who failed >=1 prior
      lines of therapy. We performed a systematic review of carfilzomib literature with
      meta-analysis to determine cumulative incidence of cardiotoxicity. After the
      literature search, we included a total of 29 eligible phase I/II, phase II and
      phase III clinical trials which used carfilzomib. The cumulative incidence and
      overall odds ratios (OR) were calculated with random effect model, using 'R'
      software with metaphor package. A total of 4164 patients with various
      malignancies were included. The overall estimated cumulative incidence of
      cardiotoxicity was 8.68% and 4.92%, respectively, for all-grade and high-grade
      (>= grade 3) toxicity, which seems higher than other PIs. Compared to control
      group, the odds of developing cardiotoxicity due to carfilzomib was significantly
      higher with OR of 2.03 (95% CI: 1.19-3.46, p = .010) and 2.04 (95% CI: 1.31-3.17,
      p = .002) for all-grades and high grades, respectively. Concomitant
      immunomodulatory agents seem to increase the risk of cardiotoxicity (high-grade
      cardiotoxicity 6.45% and 4.34% with and without concomitant immunomodulatory
      agents, respectively (p = .033)). There was no variation in the incidence of
      cardiotoxicity among newly diagnosed versus RRMM (p = .38), and high versus
      standard dose carfilzomib (p = .86).

PMID- 29465267
TI  - Elevated GLI3 expression in germinal center diffuse large B cell lymphoma.

PMID- 29465268
TI  - Convergent and discriminant validity of the Immediate Postconcussion Assessment
      and Cognitive Testing Battery (ImPACT) in young athletes.
AB  - Sports concussions are recognized as significant injuries among young athletes.
      Research demonstrates that return-to-play prior to becoming asymptomatic has
      significant repercussions including sustained cognitive deficits. Many programs
      have begun to use computerized testing rather than traditional neuropsychological
      tests to (a) determine baseline performance, (b) track symptoms, and (c) measure
      symptoms following concussion. Immediate Post-Concussion Assessment and Cognitive
      Testing (ImPACT) is one such tool. The current study examined ImPACT's convergent
      and discriminant validity by comparing scores from sports-related concussion
      athletes (SRC) to those from nonconcussed controls (CTL). SRC included 29
      athletes, ages 12-16, referred for neuropsychological assessment following sports
      related concussions. CTL included 25 healthy athletes, ages 12-16, who were
      concussion-free in the past year. Overall, results showed general support for
      ImPACT, when used to screen cognition. In fact, all ImPACT domains successfully
      differentiated between SRC and CTL athletes. Evidence supporting appropriate
      convergent validity was best for the Visual Memory domain. Further, ImPACT
      domains demonstrated variable discriminant validity. Overall examination of
      validity demonstrated that ImPACT has some weaknesses but may have utility in
      detecting postconcussion cognitive impairment.

PMID- 29465269
TI  - Evidence-Based Supplements for the Enhancement of Athletic Performance.
AB  - A strong foundation in physical conditioning and sport-specific experience, in
      addition to a bespoke and periodized training and nutrition program, are
      essential for athlete development. Once these underpinning factors are accounted
      for, and the athlete reaches a training maturity and competition level where
      marginal gains determine success, a role may exist for the use of evidence-based
      performance supplements. However, it is important that any decisions surrounding
      performance supplements are made in consideration of robust information that
      suggests the use of a product is safe, legal, and effective. The following review
      focuses on the current evidence-base for a number of common (and emerging)
      performance supplements used in sport. The supplements discussed here are
      separated into three categories based on the level of evidence supporting their
      use for enhancing sports performance: (1) established (caffeine, creatine,
      nitrate, beta-alanine, bicarbonate); (2) equivocal (citrate, phosphate,
      carnitine); and (3) developing. Within each section, the relevant performance
      type, the potential mechanisms of action, and the most common protocols used in
      the supplement dosing schedule are summarized.

PMID- 29465270
TI  - Hypomethylating agents (HMAs) effect on myelodysplastic/myeloproliferative
      neoplasm unclassifiable (MDS/MPN-U): single institution experience.

PMID- 29465271
TI  - CD38-targeting antibodies in multiple myeloma: mechanisms of action and clinical
      experience.
AB  - INTRODUCTION: Multiple myeloma (MM) is generally an incurable hematological
      malignancy with heterogeneous overall survival rates ranging from a few months to
      more than 10 years. Survival is especially poor for patients who developed
      disease that is refractory to immunomodulatory drugs and proteasome inhibitors.
      Areas covered: This review will discuss the importance of CD38-targeting
      antibodies for the treatment of MM patients to improve their outcome. Expert
      commentary: Intense immuno-oncological laboratory research has resulted in the
      development of functionally active monoclonal antibodies against cell surface
      markers present on MM cells. In this respect, CD38-targeting antibodies such as
      daratumumab, MOR202, and isatuximab, have high single agent activity in heavily
      pretreated MM patients by virtue of their pleiotropic mechanisms of action
      including Fc-dependent effector mechanisms and immunomodulatory activities.
      Importantly, CD38-targeting antibodies are well tolerated, with infusion
      reactions as most frequent adverse event. Altogether, this makes them attractive
      combination partners with other anti-MM agents. Daratumumab is already approved
      as monotherapy and in combination with lenalidomide-dexamethasone as well as
      bortezomib-dexamethasone in pretreated MM patients. Furthermore, results from
      studies evaluating CD38-targeting antibodies in newly diagnosed MM patients are
      also promising, indicating that CD38-targeting antibodies will be broadly used in
      MM, resulting in further improvements in survival.

PMID- 29465272
TI  - Freeze-all embryo strategy in poor ovarian responders undergoing ovarian
      stimulation for in vitro fertilization.
AB  - This retrospective study determined the efficacy of the 'freeze-all' embryo
      strategy in poor ovarian responders undergoing ovarian stimulation for in vitro
      fertilization (IVF). A total of 559 poor responders who met Bologna criteria
      between January 2012 and December 2014 were included in this study: 256 in the
      fresh embryo transfer group and 303 in the freeze-all group. Vitrification and
      warming of day 3 embryos were performed using the Cryotop method. The poor
      responders treated with fresh embryo transfer and those treated with freeze-all
      strategy showed similar live birth rates per cycle (12.1% vs. 16.2%, p = .172)
      and per transfer (15.9% vs. 20.9%, p = .182). Multivariate logistic regression
      analysis showed that maternal age at retrieval (odds ratio, 0.919; 95% confidence
      interval, 0.865-0.977; p = .006) and number of good-quality embryos transferred
      (odds ratio, 1.953; 95% confidence interval, 1.346-2.835; p < .001) were
      significantly associated with the live birth rate. Freeze-all cycle is an
      acceptable treatment in poor ovarian responders, and it should be suggested by
      physicians as an alternative to cycle cancelation in case in which a fresh
      transfer would not be advantageous.

PMID- 29465273
TI  - Telephone Intervention-Problem Solving (TIPS) for Schizophrenia Spectrum
      Disorders: Responses of Stable Outpatients Over Nine Months.
AB  - Medication adherence and community living problems were assessed by a telephone
      intervention for stable outpatients with schizophrenia spectrum disorders. A
      majority were white males who lived with family members. We conducted a
      descriptive analysis of data gathered during weekly calls to 87 participants
      receiving weekly TIPS for nine months. Analysis included traditional atheoretical
      content analysis, Pearson correlations, and Chi squares. The following themes
      emerged: mood disturbances and related symptoms, psychotic symptoms, coping
      problems, medication adherence, and substance cravings. The most frequently
      reported problems were mood disturbances: depression and anxiety. Forty two
      percent of Caucasians versus 72.1% of African Americans were prescribed
      intramuscular (IM) antipsychotic delivery (Chi square = 8.24, df 2, p = 0.016).
      Our findings regarding racial differences in antipsychotic delivery method
      warrant further investigation.

PMID- 29465274
TI  - Intubation Success in Critical Care Transport: A Multicenter Study.
AB  - INTRODUCTION: Tracheal intubation (TI) is a lifesaving critical care skill.
      Failed TI attempts, however, can harm patients. Critical care transport (CCT)
      teams function as the first point of critical care contact for patients being
      transported to tertiary medical centers for specialized surgical, medical, and
      trauma care. The Ground and Air Medical qUality in Transport (GAMUT) Quality
      Improvement Collaborative uses a quality metric database to track CCT quality
      metric performance, including TI. We sought to describe TI among GAMUT
      participants with the hypothesis that CCT would perform better than other
      prehospital TI reports and similarly to hospital TI success. METHODS: The GAMUT
      Database is a global, voluntary database for tracking consensus quality metric
      performance among CCT programs performing neonatal, pediatric, and adult
      transports. The TI-specific quality metrics are "first attempt TI success" and
      "definitive airway sans hypoxia/hypotension on first attempt (DASH-1A)." The 2015
      GAMUT Database was queried and analysis included patient age, program type, and
      intubation success rate. Analysis included simple statistics and Pearson chi
      square with Bonferroni-adjusted post hoc z tests (significance = p < 0.05 via two
      sided testing). RESULTS: Overall, 85,704 patient contacts (neonatal n [%] =
      12,664 [14.8%], pediatric n [%] = 28,992 [33.8%], adult n [%] = 44,048 [51.4%])
      were included, with 4,036 (4.7%) TI attempts. First attempt TI success was lowest
      in neonates (59.3%, 617 attempts), better in pediatrics (81.7%, 519 attempts),
      and best in adults (87%, 2900 attempts), p < 0.001. Adult-focused CCT teams had
      higher overall first attempt TI success versus pediatric- and neonatal-focused
      teams (86.9% vs. 63.5%, p < 0.001) and also in pediatric first attempt TI success
      (86.5% vs. 75.3%, p < 0.001). DASH-1A rates were lower across all patient types
      (neonatal = 51.9%, pediatric = 74.3%, adult = 79.8%). CONCLUSIONS: CCT TI is not
      uncommon, and rates of TI and DASH-1A success are higher in adult patients and
      adult-focused CCT teams. TI success rates are higher in CCT than other
      prehospital settings, but lower than in-hospital success TI rates. Identifying
      factors influencing TI success among high performers should influence best
      practice strategies for TI.

PMID- 29465275
TI  - Feasibility and safety of therapy with ibrutinib after antiviral control of
      hepatitis B virus (HBV) reactivation in chronic lymphocytic leukemia patients.

PMID- 29465276
TI  - Clinician perspectives and experiences in the prescription of ankle-foot orthoses
      for children with cerebral palsy.
AB  - PURPOSE: Physiotherapists, orthotists, and physicians are involved in the
      prescription of ankle-foot orthoses (AFOs) for children with cerebral palsy (CP);
      however, little is known about how prescription decisions are made in practice.
      Therefore, the study objective was to identify current AFO prescription and
      clinical decision-making practices for children with CP in Canada. METHODS: Focus
      groups were conducted in five pediatric rehabilitation facilities, with 32
      clinicians. Semi-structured interviews focused on the goals and types of AFOs
      used, referral and follow-up processes, and clinical evaluation measures.
      Interpretive Description was used as a framework for analysis. Transcribed
      dialogue was imported into NVivo 11 for data coding and analysis. Three
      researchers participated in coding to establish categories and themes. RESULTS:
      Categories included: what is made, how it is used, and factors that either
      support or challenge outcomes. Strengths and challenges of the current
      prescription process were discussed, including funding, communication, and
      technology to enhance clinical evaluation. Throughout the interviews, the theme
      of prescription as a collaborative, iterative, and individualized process
      emerged. CONCLUSIONS: Processes, strengths, and challenges associated with AFO
      prescription in Canada were identified. This is a first step toward the
      development of guidelines to help clinicians improve AFO prescription for
      children with CP.

PMID- 29465277
TI  - What Is the Impact of Targeted Health Education for Mental Health Nurses in the
      Provision of Physical Health Care? An Integrated Literature Review.
AB  - Individuals with a severe mental illness have a gap in life expectancy of up to
      twenty years in comparison to the general population. Nurses who work in mental
      health services have been identified as best placed to improve the physical
      health outcomes of individuals with mental illness. The literature identifies a
      lack of nursing knowledge related to physical health care and the presence of
      metabolic syndrome which is impeding nurses in providing essential physical
      health care to patients. An integrated literature review was carried out due to
      the dearth of research evidence pertaining to the impact of targeted education
      specifically with psychiatric/mental health nurses in the provision of physical
      healthcare. A search for literature included the following databases: CINAHL,
      Medline, PsycINFO, Embase and Web of Science revealed nine studies: seven
      quantitative, one qualitative and one mixed method. Qualitative synthesis has
      shed light on the value of targeted education on improving knowledge and skills
      in providing physical health care that can then be translated into clinical
      practice. Targeted education in physical healthcare grows psychiatric/mental
      health nurse's confidence and develops the skills necessary to enable them to
      screen and monitor and offer range of physical health interventions to
      individuals with severe mental illness. Accessible summary * The poor physical
      health outcomes and premature death of individuals with severe mental illness is
      of growing concern; a contributing factor is a lack of knowledge and confidence
      amongst psychiatric/mental health nurses to providing physical health screening
      and intervening in preventable diseases such as cardiovascular disease, stroke
      cancer, and type 2 diabetes mellitus. * An integrated literature review was used
      to ascertain if targeted education on physical health care can improve the
      knowledge base of psychiatric/mental health nurses within physical health care. *
      Nine studies were critically appraised, and the data reduced using a narrative
      synthesis that tells a story of the findings from these research studies. * The
      review found that targeted education with psychiatric/mental health nurses does
      result in a statistical increase in knowledge This review finds that nurses have
      not been regularly supported with physical health education to alter existing
      practices. This lack of knowledge within physical healthcare is hindering
      psychiatric/mental health nurses to fully engaging in physical health care
      activities in practice.

PMID- 29465278
TI  - Differences in Emotion Dysregulation and Symptoms of Depression and Anxiety among
      Illicit Substance Users and Nonusers.
AB  - BACKGROUND: Illicit substance users may rely on mind-altering substances to
      regulate affect, especially when mental health symptoms are present. OBJECTIVES:
      In light of the prevalence of illicit substance use and symptoms of depression
      and anxiety among college students, as well as the affect regulation properties
      of illicit substances, we sought to examine whether differences in emotion
      dysregulation, depression, anxiety, and stress exist between illicit substance
      users and non-users. METHODS: At a large Southwestern U.S. university, we
      examined differences in emotion dysregulation, depression, anxiety, and stress
      among college students who used illicit substances in the past 30 days (n = 92,
      34.5%) and those who did not (n = 175, 65.5%). Data were collected in 2016 using
      two measures: the Difficulties in Emotion Regulation Scale (DERS; Gratz & Roemer,
      2004) and the Depression Anxiety Stress Scales (DASS21; Lovibond & Lovibond,
      1995). RESULTS: Results from the Descriptive Discriminate Analysis (DDA)
      indicated that significant differences existed between the two groups. Anxiety,
      difficulty clarifying emotions, difficulty employing goal-directed behaviors, and
      stress accounted the most for the group differences. Conclusion/Importance:
      Mental health differences between illicit substance users and nonusers exist.
      Specifically, illicit substance users reported more anxiety, stress, and
      difficulties with emotion regulation.

PMID- 29465279
TI  - A Continuous Quality Improvement Airway Program Results in Sustained Increases in
      Intubation Success.
AB  - INTRODUCTION: Airway management is a critical skill for air medical providers,
      including the use of rapid sequence intubation (RSI) medications. Mediocre
      success rates and a high incidence of complications has challenged air medical
      providers to improve training and performance improvement efforts to improve
      clinical performance. OBJECTIVES: The aim of this research was to describe the
      experience with a novel, integrated advanced airway management program across a
      large air medical company and explore the impact of the program on improvement in
      RSI success. METHODS: The Helicopter Advanced Resuscitation Training (HeART)
      program was implemented across 160 bases in 2015. The HeART program includes a
      novel conceptual framework based on thorough understanding of physiology,
      critical thinking using a novel algorithm, difficult airway predictive tools,
      training in the optimal use of specific airway techniques and devices, and
      integrated performance improvement efforts to address opportunities for
      improvement. The C-MAC video/direct laryngoscope and high-fidelity human patient
      simulation laboratories were implemented during the study period. Chi-square test
      for trend was used to evaluate for improvements in airway management and RSI
      success (overall intubation success, first-attempt success, first-attempt success
      without desaturation) over the 25-month study period following HeART
      implementation. RESULTS: A total of 5,132 patients underwent RSI during the study
      period. Improvements in first-attempt intubation success (85% to 95%, p < 0.01)
      and first-attempt success without desaturation (84% to 94%, p < 0.01) were
      observed. Overall intubation success increased from 95% to 99% over the study
      period, but the trend was not statistically significant (p = 0.311). CONCLUSIONS:
      An integrated advanced airway management program was successful in improving RSI
      intubation performance in a large air medical company.

PMID- 29465280
TI  - Friendship and Mental Health.

PMID- 29465281
TI  - Initial Studies of Validity of the Sensory Processing 3-Dimensions Scale.
AB  - AIMS: This study examined the validity of a new measure of sensory processing for
      children, the Sensory Processing 3-Dimensions Scale (SP-3D). The SP-3D is a
      performance-based measure for children ages three to thirteen years, designed to
      assess sensory processing abilities, and identify the three patterns of sensory
      processing disorder (SPD) and related subtypes, including sensory modulation,
      sensory discrimination, and sensory-based motor disorders. METHODS: Age trends
      were explored using descriptive statistics and graphing techniques with a sample
      of children with and without SPD. SP-3D scores were correlated with scores from
      the Sensory Processing Measure (SPM) to examine criterion-related validity.
      Discriminant validity was assessed by comparing SP-3D scores from children with
      and without SPD. RESULTS: Age trends of SP-3D scores supported sensory
      discrimination, praxis and postural functions as developmental constructs.
      Several mild to moderate correlations were found between the scores of the SP-3D
      and the SPM, indicating that the tools are measuring similar constructs, and
      supporting the SP-3D as a measure of sensory processing. Modulation and Motor
      Behavior Scores from the SP-3D discriminated typically developing children from
      those with SPD, while results from subtests measuring sensory discrimination,
      postural and praxis were mixed regarding capacity for discrimination suggesting
      revision to several items. CONCLUSION: The study provides preliminary evidence of
      the SP-3D as a valid measure of sensory processing abilities and dysfunction.
      Further research regarding the reliability and validity of the SP-3D are needed.

PMID- 29465282
TI  - Typology of Nightclubs in Sao Paulo, Brazil: Alcohol and Illegal Drug
      Consumption, Sexual Behavior and Violence in the Venues.
AB  - BACKGROUND: Nightclubs are venues in which excessive alcohol use and illegal drug
      consumption occur in addition to other high-risk behaviors, such as violence and
      sexual risk behaviors. Environmental factors common in nightclubs and the
      personal characteristics of patrons might increase the risk of these events. To
      better understand the relationship between these factors, typologies were
      formulated that clustered nightclubs according to definite profiles to identify
      differences to be taken into consideration in preventive interventions.
      OBJECTIVES: The present study aim was to construct a typology of nightclubs in
      Sao Paulo, Brazil. METHODS: This typology was constructed using mixed methods
      research through the triangulation of several data sources as follows: 307 hours
      of ethnographic observation at 31 nightclubs, 8 focus group sessions with
      nightclub patrons (n = 34) and 30 semi-structured interviews with nightclub
      employees. Content analysis and qualitative typology were used. RESULTS: Four
      nightclub types were defined based on four analyzed thematic axes (Intoxicating,
      Violent, Dancing and Highly Sexualized nightclubs). Excessive alcohol use was
      detected in almost all of the investigated nightclubs, and drug use was observed
      in approximately one-third of them. Triangulation of the data revealed a
      relationship among environmental factors (especially alcohol sales strategies and
      promotion and the availability of areas for sex) and a more considerable presence
      of high-risk behaviors. CONCLUSIONS: The study shows that nightclubs are settings
      in which high-risk behaviors are potentiated by facilitating environmental
      factors as well as by the lack of laws restricting excessive alcohol use
      stimulated by the promotion strategies applied at these venues.

PMID- 29465283
TI  - Augmented reality in dentistry: a current perspective.
AB  - Augmentation reality technology offers virtual information in addition to that of
      the real environment and thus opens new possibilities in various fields. The
      medical applications of augmentation reality are generally concentrated on
      surgery types, including neurosurgery, laparoscopic surgery and plastic surgery.
      Augmentation reality technology is also widely used in medical education and
      training. In dentistry, oral and maxillofacial surgery is the primary area of
      use, where dental implant placement and orthognathic surgery are the most
      frequent applications. Recent technological advancements are enabling new
      applications of restorative dentistry, orthodontics and endodontics. This review
      briefly summarizes the history, definitions, features, and components of
      augmented reality technology and discusses its applications and future
      perspectives in dentistry.

PMID- 29465284
TI  - Accuracy of Intravenous Infusion Flow Regulators in the Prehospital Environment.
AB  - OBJECTIVE: To assess the accuracy of multiple Intravenous Infusion Flow
      Regulators (IIFRs) at infusion rates and hanging heights common to the
      prehospital setting. METHODS: Five different manufacturer's IIFRs were tested
      over a range of infusion rates while hanging at heights equivalent to the gurney
      pole, ambulance ceiling hook, and manufacturer's recommended height (if
      available). Each IIFR was run over a 15-minute period at each infusion rate and
      height three times. Drip effluent was collected and measured for comparison of
      volumes. Intra- and inter-device accuracy at different infusion rates and heights
      was calculated. RESULTS: All devices deviated from the expected infusion volume
      regardless of infusion rate or height. There was inter-device variability across
      all IIFRs with some having reproducible though inaccurate volumes. Volumes were
      consistently below expected at lower heights and above expected at increased
      heights. Manufacturer recommended height guidelines provided slight improvements
      in accuracy. CONCLUSIONS: Significant deviations from expected IIFR volume were
      observed across all devices, flow rates, and heights in a static, laboratory
      environment. These findings would lend caution to the use of IIFRs as they could
      lead to inaccurate medication dosing (both over- or under-dosing) in the
      prehospital environment.

PMID- 29465285
TI  - Depressive Symptoms and Suicidal Ideation among Irish Undergraduate College
      Students.
AB  - This study examined the prevalence of depressive symptoms and suicidal ideation
      among 220 first year undergraduate university students in Ireland. Data were
      collected using the Centre for Epidemiological Studies Depression Scale and the
      Suicidal Behaviours Questionnaire. Findings indicated that 59% of participants
      experienced depressive symptoms and 28.5% had suicidal ideation. Financial stress
      and poor relationships with both parents, increased the odds of experiencing
      depressive symptoms. Sexual orientation, financial stress, and poor relationships
      with fathers, increased the odds of experiencing suicidal ideation. Suicidal
      ideation was also higher in those who had sought help in the past from mental
      health professionals. Nurses need to be aware of the factors associated with
      mental ill-health in this population.

PMID- 29465286
TI  - Genetic association of single nucleotide polymorphisms of FZD4 and BDNF genes
      with retinopathy of prematurity.
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial disease
      occurring in preterm neonates, caused by incorrect development of retinal blood
      vessels. It has been suggested that, in addition to gestational age, weight, and
      oxygen supplementation, genetic factors can play a role in the pathogenesis of
      ROP. METHODS: In the present prospective study, 97 neonates were enrolled based
      on the gestational age and weight, and genomic DNA from patients diagnosed with
      ROP and premature newborns without ROP was collected. The DNA sequence of protein
      coding and 5'and 3' untranslated regions (UTRs) of the frizzled-4 (FZD4) gene and
      the genotype of the locus rs7934165:G?A (NM_170731.4: c.3 + 10976 C?T) within the
      brain-derived neurotrophic factor gene (BDNF) were determined. RESULTS: We
      detected a significant association between rs61749246:C?A (NM_012193.3: c.*2G?T)
      and ROP in a general genetic model as well as in a multiplicative model and by
      the Cochran-Armitage test for trend. Moreover, rs61749246 was strongly associated
      with ROP, requiring surgical intervention. CONCLUSION: We suggest that
      rs61749246:C?A of the FZD4 gene is likely associated with the development of ROP.
      It is necessary to confirm this suggestion in larger studies.

PMID- 29465288
TI  - Origin and Consequences of Necroinflammation.
AB  - When cells undergo necrotic cell death in either physiological or
      pathophysiological settings in vivo, they release highly immunogenic
      intracellular molecules and organelles into the interstitium and thereby
      represent the strongest known trigger of the immune system. With our increasing
      understanding of necrosis as a regulated and genetically determined process (RN,
      regulated necrosis), necrosis and necroinflammation can be pharmacologically
      prevented. This review discusses our current knowledge about signaling pathways
      of necrotic cell death as the origin of necroinflammation. Multiple pathways of
      RN such as necroptosis, ferroptosis, and pyroptosis have been evolutionary
      conserved most likely because of their differences in immunogenicity. As the
      consequence of necrosis, however, all necrotic cells release damage associated
      molecular patterns (DAMPs) that have been extensively investigated over the last
      two decades. Analysis of necroinflammation allows characterizing specific
      signatures for each particular pathway of cell death. While all RN-pathways share
      the release of DAMPs in general, most of them actively regulate the immune system
      by the additional expression and/or maturation of either pro- or anti
      inflammatory cytokines/chemokines. In addition, DAMPs have been demonstrated to
      modulate the process of regeneration. For the purpose of better understanding of
      necroinflammation, we introduce a novel classification of DAMPs in this review to
      help detect the relative contribution of each RN-pathway to certain physiological
      and pathophysiological conditions.

PMID- 29465287
TI  - The exoribonuclease Xrn1 is a post-transcriptional negative regulator of
      autophagy.
AB  - Macroautophagy/autophagy is a conserved catabolic process that promotes survival
      during stress. Autophagic dysfunction is associated with pathologies such as
      cancer and neurodegenerative diseases. Thus, autophagy must be strictly modulated
      at multiple levels (transcriptional, post-transcriptional, translational and post
      translational) to prevent deregulation. Relatively little is known about the post
      transcriptional control of autophagy. Here we report that the exoribonuclease
      Xrn1/XRN1 functions as a negative autophagy factor in the yeast Saccharomyces
      cerevisiae and in mammalian cells. In yeast, chromosomal deletion of XRN1
      enhances autophagy and the frequency of autophagosome formation. Loss of Xrn1
      results in the upregulation of autophagy-related (ATG) transcripts under nutrient
      replete conditions, and this effect is dependent on the ribonuclease activity of
      Xrn1. Xrn1 expression is regulated by the yeast transcription factor Ash1 in rich
      conditions. In mammalian cells, siRNA depletion of XRN1 enhances autophagy and
      the replication of 2 picornaviruses. This work provides insight into the role of
      the RNA decay factor Xrn1/XRN1 as a post-transcriptional regulator of autophagy.

PMID- 29465290
TI  - Global, integrated analysis of methylomes and transcriptomes from laser capture
      microdissected bronchial and alveolar cells in human lung.
AB  - Gene regulatory analysis of highly diverse human tissues in vivo is essentially
      constrained by the challenge of performing genome-wide, integrated epigenetic and
      transcriptomic analysis in small selected groups of specific cell types. Here we
      performed genome-wide bisulfite sequencing and RNA-seq from the same small groups
      of bronchial and alveolar cells isolated by laser capture microdissection from
      flash-frozen lung tissue of 12 donors and their peripheral blood T cells.
      Methylation and transcriptome patterns differed between alveolar and bronchial
      cells, while each of these epithelia showed more differences from mesodermally
      derived T cells. Differentially methylated regions (DMRs) between alveolar and
      bronchial cells tended to locate at regulatory regions affecting promoters of
      4,350 genes. A large number of pathways enriched for these DMRs including GTPase
      signal transduction, cell death, and skeletal muscle. Similar patterns of
      transcriptome differences were observed: 4,108 differentially expressed genes
      (DEGs) enriched in GTPase signal transduction, inflammation, cilium assembly, and
      others. Prioritizing using DMR-DEG regulatory network, we highlighted genes,
      e.g., ETS1, PPARG, and RXRG, at prominent alveolar vs. bronchial cell
      discriminant nodes. Our results show that multi-omic analysis of small, highly
      specific cells is feasible and yields unique physiologic loci distinguishing
      human lung cell types in situ.

PMID- 29465291
TI  - Men's hopes, fears and challenges in engagement in perinatal health and the
      prevention of mother-to-child transmission of HIV in rural Kenya.
AB  - Male involvement in antenatal care has been shown to improve health outcomes for
      women and infants. However, little is known about how best to encourage male
      partners to support essential perinatal health activities. We explored men's
      perceptions of facilitators and barriers to involvement in antenatal care and HIV
      prevention including fears, hopes and challenges. Forty in-depth interviews were
      conducted with the male partners of HIV-positive and HIV-negative pregnant women
      in southwest Kenya. Most male partners believed engaging in pregnancy health
      related activities was beneficial for keeping families healthy. However, thematic
      analysis revealed several obstacles that hindered participation. Poor couple
      relationship dynamics seemed negatively to influence male engagement. Some men
      were apprehensive that clinic staff might force them to test for HIV and disclose
      the results; if HIV-positive, men feared being labelled as 'victimisers' in
      situations of serodiscordancy, and described fears of abandonment by their wives.
      Some men avoided accompanying their wives, citing local culture as rationale for
      avoiding the 'effeminate' act of antenatal care attendance. Amidst these
      obstacles, some men chose to use their partners' HIV status as proxy for their
      own. Findings suggest that improving male engagement in essential maternal and
      child health-related activities will require addressing both structural and
      interpersonal barriers.

PMID- 29465292
TI  - An unusual case of sudden cardiac death during sexual intercourse.
AB  - The most common cause of sudden death during sexual intercourse in adults is
      heart disease, and it is usually the male, whereas the death of the woman is
      unusual. Generally, in these cases, death occurs as a result of cardiovascular
      disease. The authors report an unusual case of the sudden death of a young woman
      during sexual intercourse. The post-mortem investigations (autopsy, cardiac
      nuclear magnetic resonance and cardiac histology) demonstrated a previously
      undiagnosed arrhythmogenic right ventricular cardiomyopathy. The terminal cause
      of death was a malignant arrhythmia from arrhythmogenic right ventricular
      cardiomyopathy. This is the first report of a case in which sexual activity can
      be regarded as the triggering factor combined with cardiac disease to the woman's
      death.

PMID- 29465293
TI  - Effectiveness of a physical activity program on weight, physical fitness,
      occupational stress, job satisfaction and quality of life of overweight employees
      in high-tech industries: a randomized controlled study.
AB  - INTRODUCTION: This study aimed to examine the effectiveness of a physical
      activity (PA) program on weight control, physical fitness, occupational stress,
      job satisfaction and quality of life of overweight and sedentary employees in
      high-tech industries. METHODS: Participants in the intervention group (n = 37)
      were instructed to carry out a PA program at moderate intensity for 60
      min/session, 3 sessions/week for 12 weeks. Those in the control group (n = 38)
      received no PA program and were asked to continue their routine lifestyle.
      Evaluations were performed at baseline and at the end of the intervention.
      Results of structured questionnaires and blood biochemistry tests and evaluations
      of physical fitness were analyzed. RESULTS: The PA program effectively reduced
      the number of risk factors for metabolic syndrome and body fat percentage, and
      improved physical fitness such as flexibility, muscular strength and endurance
      and cardiorespiratory endurance. The intervention also significantly decreased
      levels of serum triglyceride, total cholesterol and low-density lipoprotein
      cholesterol. Significant positive effects on work control, interpersonal
      relationships at work, global job satisfaction and quality of life were also
      demonstrated. CONCLUSION: This study showed that a PA program can be helpful in
      improving physical, physiological and psychological outcomes for overweight and
      sedentary employees in high-tech industries.

PMID- 29465294
TI  - Occupational health risk assessment of volatile organic compounds emitted from
      the coke production unit of a steel plant.
AB  - In this study, cancer and non-cancer risks of exposure to volatile organic
      compounds in the coke production unit of a steel plant were evaluated. To
      determine individual exposure to benzene, toluene, xylene and ethylbenzene,
      personal samples were taken from the breathing zone of workers according to
      National Institute for Occupational Safety and Health (NIOSH) method 1501. Cancer
      and non-cancer risk assessment was performed, using US Environmental Protection
      Agency (US EPA) methods. Samples analysis showed that the concentration of
      benzene in the energy and biochemistry and the benzol refinement sections was
      higher than occupational exposure limits. The cancer risk for benzene in all
      sections was significantly higher than allowable limit; the non-cancer risk for
      benzene in all sections and toluene in the benzol refinement section was also
      higher than 1.0. In conclusion, the current control measures are not sufficient
      and should be improved for efficient control of occupational exposures.

PMID- 29465295
TI  - Predicting complicated outcomes in spinal cord injury patients with urinary tract
      infection: Development and internal validation of a risk model.
AB  - CONTEXT/OBJECTIVE: Patients with chronic SCI hospitalized for UTI can have
      significant morbidity. It is unclear whether SIRS criteria, SOFA score, or quick
      SOFA score can be used to predict complicated outcome. DESIGN: Retrospective
      cohort study. A risk prediction model was developed and internally validated
      using bootstrapping methodology. SETTING: Urban, academic hospital in St. Louis,
      Missouri. PARTICIPANTS: 402 hospitalizations for UTI between October 1, 2010 and
      September 30, 2015, arising from 164 patients with chronic SCI, were included in
      the final analysis. Outcome/measures: An a priori composite complicated outcome
      defined as: 30-day hospital mortality, length of hospital stay >4 days, intensive
      care unit (ICU) admission, and hospital revisit within 30 days of discharge.
      RESULTS: Mean age of patients was 46.4 +/- 12.3 years; 83.6% of patient-visits
      involved males. The primary outcome occurred in 278 (69.2%) hospitalizations. In
      multivariate analysis, male sex was protective (odds ratio [OR], 0.43; 95%
      confidence interval [CI], 0.18-0.99; P = 0.048) while Gram-positive urine culture
      (OR 3.07; 95% CI, 1.05-9.01; P = 0.041), urine culture with no growth (OR, 1.69;
      95% CI, 1.02-2.80; P = 0.041), and greater SOFA score (for one-point increments,
      OR, 1.41; 95% CI, 1.18-1.69; P < 0.001) were predictive for complicated outcome.
      SIRS criteria and qSOFA score were not associated with complicated outcome. Our
      risk prediction model demonstrated good overall performance (Brier score, 0.19),
      fair discriminatory power (c-index, 0.72), and good calibration during internal
      validation. CONCLUSION: Clinical variables present on hospital admission with UTI
      may help identify SCI patients at risk for complicated outcomes and inform future
      clinical decision-making.

PMID- 29465296
TI  - Airlift bioreactor system for simultaneous removal of hydrogen sulfide and
      ammonia from synthetic and actual waste gases.
AB  - The effectiveness of an airlift reactor system in simultaneously removing
      hydrogen sulfide (H2S) and ammonia (NH3) from synthetic and actual waste gases
      was investigated. The effects of various parameters, including the ratio of
      inoculum dilution, the gas concentration, the gas retention time, catalyst
      addition, the bubble size, and light intensity, on H2S and NH3 removal were
      investigated. The results revealed that optimal gas removal could be achieved by
      employing an activated inoculum, using a small bubble stone, applying reinforced
      fluorescent light, adding Fe2O3 catalysts, and applying a gas retention time of
      20 s. The shock loading did not substantially affect the removal efficiency of
      the airlift bioreactor. Moreover, more than 98.5% of H2S and 99.6% of NH3 were
      removed in treating actual waste gases. Fifteen bands or species were observed in
      a profile from denaturing gradient gel electrophoresis during waste gas
      treatment. Phylogenetic analysis revealed the phylum Proteobacteria to be
      predominant. Six bacterial strains were consistently present during the entire
      operating period; however, only Rhodobacter capsulatus, Rhodopseudomonas
      palustris, and Arthrobacter oxydans were relatively abundant in the system. The
      photosynthetic bacteria R. capsulatus and R. palustris were responsible for H2S
      oxidation, especially when the reinforced fluorescent light was used. The
      heterotrophic nitrifier A. oxydans was responsible for NH3 oxidation. To our
      knowledge, this is the first report on simultaneous H2S and NH3 removal using an
      airlift bioreactor system. It clearly demonstrates the effectiveness of the
      system in treating actual waste gases containing H2S and NH3.

PMID- 29465297
TI  - Model based evaluation of plant improvement at a large wastewater treatment plant
      (WWTP).
AB  - In this work, the effect of the improvement carried out at a large-scale
      wastewater treatment plant (WWTP) was evaluated, by means of modelling works,
      with the aim to determine the influence of the modernization over the process
      performance. After modernization, the energy consumption due to the aeration
      decreased about a 20% maintaining the effluent quality. In order to double-check
      the good effluent quality, modelling works were carried out at the full-scale
      plant. After calibration, the model was applied to the upgraded full-scale plant
      obtaining deviations lower than 10%. Then, the performance of the main
      biochemical processes was evaluated in terms of oxygen uptake rate (OUR), ammonia
      uptake rate (AUR), and chemical oxygen demand (COD) consumption. The rate of the
      main processes depending on the aeration, that is OUR and AUR, were about 22
      gO2/(kg VSS.h) and 2.9 gN/(kg VSS.h), respectively.

PMID- 29465298
TI  - The determination of the validity of an application-based knee-training device.
AB  - The goals of knee rehabilitation are to improve range of motion and muscle
      status. The aim of the study was to investigate accuracy and reproducibility of a
      newly designed knee-training device (KT) under standardized laboratory
      conditions. Two application-based software programs, one to measure maximum force
      and the other intended to improve users' coordination were developed to be used
      on a tablet during exercises, wirelessly connected to KT placed under the
      popliteal fossa. KT was loaded for 20 intervals of 15 seconds (s) ranging between
      0-350 Newton (N) each. The interval of times was chosen to be enough to take
      right measurement for accurate results. In addition, a 300-s continuous
      measurement was undertaken. The pressure readings were developed through a servo
      hydraulic system and used as reference values. KT results were compared with the
      reference values to assess its accuracy. In addition, KT was tested on a force
      measuring platform in a close to reality measurement. Based on Bland-Altman
      plots, the mean difference between KT and material testing machine was -0.63 N
      (0.4%), between KT and force-measuring platform was -0.11 N (0.7%), which proves
      the accuracy of its result. Laboratory experiments confirm that KT delivers
      precise and reproducible values, which provide base for clinical trials.

PMID- 29465299
TI  - Down's Syndrome Screening and Reproductive Politics: Care, Choice, and Disability
      in the Prenatal Clinic.

PMID- 29465300
TI  - With the End in Mind: Dying, Death and Wisdom in an Age of Denial.

PMID- 29465301
TI  - Socioeconomic and geographical disparities in prescription and illicit opioid
      related overdose deaths in Orange County, California, from 2010-2014.
AB  - BACKGROUND: Reports indicate a geographic effect of socioeconomic inequalities on
      the occurrence of opioid-related fatal overdoses. This study aims to (1) estimate
      the rates of opioid-related overdoses, (2) estimate the association of
      benzodiazepine co-ingestion with opioid-related deaths, (3) estimate associations
      between socioeconomic indicators and opioid-related deaths, and (4) map the
      distribution of fatal overdoses, in Orange County (OC), California. METHODS: An
      ecologic study was conducted of all opioid- related deaths (1205 total) from 2010
      to 2014 obtained from the OC Coroner Division database (1065 OC residents, 55
      nonresidents, 85 OC homeless) (analyzed 2016-2017). Rates of opioid overdose,
      benzodiazepine co-ingestion prevalence, and associations with socioeconomic
      status (SES; education, poverty, median income) using ZIP code analysis in the
      residential and homeless communities were calculated. RESULTS: Of 1205 deaths,
      904 involved prescription-type opioids, 223 involved heroin, 39 involved both,
      and 39 not stated; 973 were classified unintentional overdoses, 180 suicides, and
      52 undetermined; 49% of cases involved benzodiazepines. Prescription-type opioid
      and heroin death rates for residents were 5.4/ 100,000 person-years (95%
      confidence interval [CI]: 5.0-5.8) and 1.2/100,000 person-years (95% CI: 1.0
      1.4), respectively. Males, age group 45-54, and Caucasian race had the highest
      rate (13.6/100,000) of opioid mortality. The highest death rates were seen in
      homeless adults, at 136/100,000 person-years for prescription-type opioids (95%
      CI: 99.0-185.5) and 156/100,000 person-years for heroin (95% CI: 116.8-209.5).
      CONCLUSIONS: The burden of prescription-type opioid-related deaths in OC affects
      all demographics and levels of SES; there is a disproportionately high rate of
      opioid-related deaths in the OC homeless population.

PMID- 29465302
TI  - Merits and complexities of modeling multiple sclerosis in non-human primates:
      implications for drug discovery.
AB  - INTRODUCTION: The translation of scientific discoveries made in animal models
      into effective treatments for patients often fails, indicating that currently
      used disease models in preclinical research are insufficiently predictive for
      clinical success. An often-used model in the preclinical research of autoimmune
      neurological diseases, multiple sclerosis in particular, is experimental
      autoimmune encephalomyelitis (EAE). Most EAE models are based on genetically
      susceptible inbred/SPF mouse strains used at adolescent age (10-12 weeks), which
      lack exposure to genetic and microbial factors which shape the human immune
      system. Areas covered: Herein, the authors ask whether an EAE model in adult non
      human primates from an outbred conventionally-housed colony could help bridge the
      translational gap between rodent EAE models and MS patients. Particularly, the
      authors discuss a novel and translationally relevant EAE model in common
      marmosets (Callithrix jacchus) that shares remarkable pathological similarity
      with MS. Expert opinion: The MS-like pathology in this model is caused by the
      interaction of effector memory T cells with B cells infected with the gamma1
      herpesvirus (CalHV3), both present in the pathogen-educated marmoset immune
      repertoire. The authors postulate that depletion of only the small subset
      (<0.05%) of CalHV3-infected B cells may be sufficient to limit chronic
      inflammatory demyelination.

PMID- 29465303
TI  - Morphologic and morphometric study on microvasculature of developing mouse
      kidneys.
AB  - A proper morphogenesis of the renal microvasculature is crucial not only for
      fulfilling the renal function but also to slow down the progression of chronic
      kidney disease in adulthood. However, the current description of the developing
      microvasculature is incomplete. The present study investigated the morphogenesis
      and volume densities of the renal microvasculature using computer-assisted
      tubular tracing, immunohistochemistry for CD34, and unbiased stereology. The
      earliest glomerular capillaries were observed at the lower cleft of the S-shaped
      nephrons, as simple loops connecting the afferent and efferent arterioles. In
      parallel with this, the peritubular capillaries were established. Noticeably,
      from early nephrogenesis on, the efferent arterioles of the early-formed
      glomeruli ran in close proximity to their own thick ascending limbs. In addition,
      the ascending vasa recta arising from the arcuate or interlobular veins also ran
      in close proximity to the thick descending limb. Thus, the tubules and vessels
      formed the typical countercurrent relation in the medulla. No loop bends were
      observed between descending and ascending vasa recta. The volume density of the
      cortical and medullary peritubular capillary increased 3.3- and 2.6-fold,
      respectively, from 2.34 (0.13) and 7.03 (0.09)% [means (SD)] at embryonic day
      14.5 (E14.5) to 7.71 (0.44) and 18.27 (1.17)% at postnatal day 40 (P40). In
      contrast, the volume density of glomeruli changed only slightly during kidney
      development, from 4.61 (0.47)% at E14.5 to 6.07 (0.2)% at P7 to 4.19 (0.47)% at
      P40. These results reflect that the growth and formation of the renal
      microvasculature closely correspond to functional development of the tubules.

PMID- 29465304
TI  - A MAPP Network study: overexpression of tumor necrosis factor-alpha in mouse
      urothelium mimics interstitial cystitis.
AB  - Interstitial cystitis/bladder pain syndrome is a chronic bladder condition
      associated with pain and voiding dysfunction that is often regarded as a
      neurogenic cystitis. Patient symptoms are correlated with the presence of
      urothelial lesions. We previously characterized a murine neurogenic cystitis
      model that recapitulates mast cell accumulation and urothelial lesions, and these
      events were dependent on TNF. To further explore the role of TNF in bladder
      inflammation and function, we generated a transgenic mouse model with chronic TNF
      overexpression in urothelium under the control of the uroplakin II (UPII)
      promoter. Transgenic mouse lines were maintained by backcross onto wild-type
      C57BL/6J mice and evaluated for pelvic tactile allodynia as a measure of visceral
      pain, urinary function, and urothelial lesions. TNF mRNA and protein were
      expressed at greater levels in bladders of UPII-TNF mice than in those of wild
      type mice. UPII-TNF mice showed significantly increased urinary frequency and
      decreased void volume. UPII-TNF mice had increased urothelial apoptosis and loss
      of urothelial integrity consistent with urothelial lesions. Overexpression of TNF
      was also associated with pelvic tactile allodynia. Consistent with these
      findings, UPII-TNF mice exhibited increased bladder afferent activity in response
      to stretch ex vivo. In summary, UPII-TNF mice display significant pelvic pain,
      voiding dysfunction, urothelial lesions, and sensory input. Thus UPII-TNF mice
      are a model for characterizing mechanisms of interstitial cystitis symptoms and
      evaluating therapies.

PMID- 29465305
TI  - Glomerular hyperpermeability after acute unilateral ureteral obstruction: effects
      of Tempol, NOS, RhoA, and Rac-1 inhibition.
AB  - It is well known that proteinuria following urinary tract obstruction is mainly
      of a tubular nature. However, it is unknown whether there are also changes in
      glomerular permeability. In this study, we compared glomerular sieving
      coefficients (theta) of polydisperse fluorescein isothiocyanate (FITC)-Ficoll
      70/400 following a 120- or 180-min unilateral ureteral obstruction (UUO) in
      anesthetized Sprague-Dawley rats. Samples were collected from the obstructed
      kidney at 5, 15, and 30 min postrelease and analyzed by means of high-pressure
      size-exclusion chromatography. After 120-min UUO, mean theta for Ficoll70A was
      increased ( P < 0.01) from 2.2 +/- 0.5 * 10-5 (baseline) to 10.6 +/- 10 * 10-5 15
      min postrelease (highest value). After 180-min UUO, mean theta for Ficoll70A was
      further increased ( P < 0.001) from 1.4 +/- 0.5 * 10-5 (baseline) to 40 +/- 10 *
      10-5 at 5 min postrelease (highest value). Administration of a reactive oxygen
      species (ROS) scavenger (Tempol; 1 mg.kg-1.min-1) partly abrogated the
      permeability effects following 120-min UUO but not after 180 min. Moreover,
      administration of the RhoA kinase inhibitor Y-27632, the nitric oxide synthase
      inhibitor NG-nitro-l-arginine methyl ester, or Rac-1 inhibition did not
      ameliorate glomerular hyperpermeability following 180-min UUO. We show, for the
      first time, that acute UUO results in marked elevations in glomerular
      permeability. In addition, our data suggest a time-dependent pathophysiology of
      UUO-induced hyperpermeability, where reactive oxygen species generation may play
      an important role in the early stages.

PMID- 29465306
TI  - Sex dimorphism in the distribution of adipose tissue and its influence on
      proinflammatory adipokines and cardiometabolic profiles in motor complete spinal
      cord injury.
AB  - OBJECTIVE: We aimed to examine the influence of sex on the distribution of
      adipose tissue, as well as proinflammatory adipokine and cardiometabolic
      profiles, in chronic motor complete spinal cord injury (SCI). DESIGN: Cross
      sectional and correlational study. SETTING: Academic rehabilitation hospital.
      PARTICIPANTS: Forty-seven individuals with chronic motor complete SCI classified
      according to sex (males: age 44.0 +/- 10.9 y, body mass index (BMI) 27.2 +/- 5.8,
      level of injury (LOI) C4 - L1; females: 42.0 +/- 13.5 y, BMI 27.8 +/- 6.6, LOI C4
      - T11). INTERVENTION: Not applicable. OUTCOME MEASURES: Visceral (VAT),
      subcutaneous (SAT), and total trunk (TTAT) adipose tissue volumes were assessed
      utilizing magnetic resonance imaging and a VAT:SAT ratio was calculated.
      Proinflammatory adipokines (tumor neurosis factor-alpha, interleukin-6,
      plasminogen activator inhibitor-1, thrombin-activatable fibrinolysis inhibitor,
      and high sensitivity c-reactive protein) and cardiovascular, carbohydrate, and
      lipid profiles were evaluated according to standard techniques. RESULTS: VAT and
      VAT:SAT ratio were significantly greater in male participates with SCI (P <=
      0.002), while SAT volume was significantly greater in female participants with
      SCI (P = 0.001). No difference was noted in TTAT between groups (P = 0.341). Male
      participants with SCI demonstrated lower high-density lipoprotein-cholesterol
      (HDLC) profiles and an elevated total cholesterol to HDLC ratio (P <= 0.003)
      compared with females. No other significant differences were found between groups
      concerning cardiometabolic profiles or proinflammatory adipokines; however, males
      exhibited poorer profiles overall. Proinflammatory adipokines significantly
      correlated with adipose tissue depots by sex (P < 0.05). CONCLUSION: The results
      show that sex influences the distribution of adipose tissue, and may influence
      proinflammatory and cardiometabolic profiles following SCI. The findings of this
      study highlight the need for further research with dietary modification and
      exercise to decrease health risks.

PMID- 29465307
TI  - Sensory sensitivity and posttraumatic stress disorder in blast exposed veterans
      with mild traumatic brain injury.
AB  - The purpose of this study was to examine the unique contribution of posttraumatic
      stress disorder (PTSD) symptoms on sensory sensitivity following mild traumatic
      brain injury (mTBI) in an Operation Enduring Freedom and Operation Iraqi Freedom
      (OEF/OIF) Veteran sample. We hypothesized that the effect of PTSD on noise and
      light sensitivity following mTBI would be largely driven by PTSD-related
      hyperarousal symptoms. We compared the relationships between PTSD, noise
      sensitivity, and light sensitivity of 49 OEF/OIF Veterans with mTBI to that of 23
      OEF/OIF Veterans without mTBI. Results suggest that intrusive experiences were
      significantly related to noise sensitivity in the mTBI group, while light
      sensitivity was significantly associated with avoidance. Hyperarousal symptoms
      significantly accounted for noise sensitivity in the no-blast, non-TBI group,
      whereas PTSD did not affect light sensitivity in this group. These data suggest
      that PTSD symptoms may uniquely influence the experience of noise and light
      sensitivity. As such, treatment targeting specific PTSD symptoms may yield
      clinically significant improvement in sensory sensitivity.

PMID- 29465309
TI  - An unusual, CD4 and CD8 dual-positive, CD25 negative, tumor cell phenotype in a
      patient with adult T-cell leukemia/lymphoma.

PMID- 29465308
TI  - CLL2-BXX Phase II trials: sequential, targeted treatment for eradication of
      minimal residual disease in chronic lymphocytic leukemia.
AB  - AIM: Four Phase II trials (clinical trials numbers: NCT02345863, NCT02401503,
      NCT02445131 and NCT02689141) evaluate a different combination of targeted agents
      in an all-comer population of approximately 60 patients with chronic lymphocytic
      leukemia irrespective of prior treatment, physical fitness and genetic risk
      factors. Patients with a higher tumor load start with a debulking treatment with
      bendamustine. The subsequent induction and maintenance treatment with an anti
      CD20 antibody (obinutuzumab or ofatumumab) and a targeted oral agent (ibrutinib,
      idelalisib or venetoclax) are continued until achievement of a complete response
      and minimal residual disease negativity. CONCLUSION: This strategy represents a
      new era of chronic lymphocytic leukemia therapy where chemotherapy is
      increasingly replaced by targeted agents and treatment duration is tailored to
      the patient's individual tumor load and response.

PMID- 29465310
TI  - Dietary starch breakdown product sensing mobilizes and apically activates alpha
      glucosidases in small intestinal enterocytes.
AB  - Dietary starch is finally converted to glucose for absorption by the small
      intestine mucosal alpha-glucosidases (sucrase-isomaltase [SI] and maltase
      glucoamylase), and control of this process has health implications. Here, the
      molecular mechanisms were analyzed associated with starch-triggered maturation
      and transport of SI. Biosynthetic pulse-chase in Caco-2 cells revealed that the
      high MW SI species (265 kDa) induced by maltose (an alpha-amylase starch
      digestion product) had a higher rate of early trafficking and maturation compared
      with a glucose-induced SI (245 kDa). The maltose-induced SI was found to have
      higher affinity to lipid rafts, which are associated with enhanced targeting to
      the apical membrane and higher activity. Accordingly, in situ maltose-hydrolyzing
      action was enhanced in the maltose-treated cells. Thus, starch digestion products
      at the luminal surface of small intestinal enterocytes are sensed and accelerate
      the intracellular processing of SI to enhance starch digestion capacity in the
      intestinal lumen.-Chegeni, M., Amiri, M., Nichols, B. L., Naim, H. Y., Hamaker,
      B. R. Dietary starch breakdown product sensing mobilizes and apically activates
      alpha-glucosidases in small intestinal enterocytes.

PMID- 29465311
TI  - p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
AB  - Sustained endoplasmic reticulum (ER) stress plays a major role in the development
      of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty
      liver disease, insulin resistance, obesity, and diabetes. p32 is a
      multicompartmental protein involved in the regulation of oxidative
      phosphorylation and glucose oxidation. p32 ablation is associated with resistance
      to age-associated and diet-induced obesity through a mechanism that remains
      largely unknown. Here, we show that p32 promotes lipid biosynthesis by modulating
      fatty acid-induced ER stress. We found that p32 interacts with endoplasmic
      reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER
      lumen-anchored glucosidase that is essential for the processing of N-linked
      glycoproteins, and reduces GCS1 in a lysosome-dependent manner. We demonstrate
      that increased GCS1 expression alleviates fatty acid-induced ER stress and is
      critical for suppressing ER stress-associated lipogenic gene activation, as
      demonstrated by the down-regulation of Srebp1, Fasn, and Acc. Consistently,
      suppression of p32 leads to increased GCS1 expression and alleviates fatty acid
      induced ER stress, resulting in reduced lipid accumulation. Thus, p32 and GCS1
      are regulators of ER function and lipid homeostasis and are potential therapeutic
      targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin,
      A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid
      homeostasis by down-regulating GCS1 expression.

PMID- 29465312
TI  - Identification of a TGF-beta-miR-195 positive feedback loop in hepatocytes and
      its deregulation in hepatoma cells.
AB  - Resistance to TGF-beta-induced growth repression is prevalent in various cancer
      cells, but the underlying mechanisms remain unclear. In this study, we showed
      that activation of TGF-beta signaling caused Sma- and Mad-related family (Smad) 2
      and Smad3 to bind directly to the promoter region of miR-195, and then activated
      miR-195 transcription in normal hepatocytes. Conversely, miR-195 inhibited the
      expression of Smad7 by binding to its 3'-UTR, thereby strengthening TGF-beta-Smad
      signaling. These data identify a novel TGF-beta-miR-195 positive regulatory
      circuitry in normal hepatocytes. Further investigation revealed that HDAC1, a
      histone deacetylase that was abnormally overexpressed in hepatocellular
      carcinoma, could bind to the miR-195 promoter via Smad3 and cause hypoacetylation
      in the histones associated with the miR-195 promoter in hepatoma cells. This
      resulted in transcriptional repression of miR-195 and, subsequently, disruption
      of the TGF-beta-miR-195 regulatory loop and evasion of TGF-beta-mediated growth
      inhibition. Moreover, silencing HDAC1 in hepatoma cells restored TGF-beta
      mediated growth suppression, but this effect was attenuated if miR-195 expression
      decreased. These findings suggest that HDAC1-induced miR-195 down-regulation is
      an important mechanism for tumor cells to resist the cytostatic activity of TGF
      beta, and highlight the importance of TGF-beta-Smad2/3-miR-195-Smad7 circuitry in
      preventing uncontrolled cell proliferation.-Wang, R., Fu, T., You, K., Li, S.,
      Zhao, N., Yang, J., Zhuang, S.-M. Identification of a TGF-beta-miR-195 positive
      feedback loop in hepatocytes and its deregulation in hepatoma cells.

PMID- 29465313
TI  - CD5L is upregulated in hepatocellular carcinoma and promotes liver cancer cell
      proliferation and antiapoptotic responses by binding to HSPA5 (GRP78).
AB  - CD5-like (CD5L) is a soluble scavenger cysteine-rich protein that modulates
      inflammatory responses. We studied the involvement of CD5L in liver cancer.
      Immunohistochemistry (IHC) of CD5L in 60 hepatocellular carcinomas and 34
      adjacent nontumor livers, showed that CD5L staining was higher in tumor than in
      nontumor tissue (Mann-Whitney test; P = 0.0039). High CD5L correlated with
      elevated proliferation (Ki67, linear regression; P < 0.0001) and lower patient
      event-free survival (log-rank; P = 0.0185). Accordingly, CD5L expression was
      detected in the liver cancer cell lines Huh7, HepG2, and SNU-398. In vitro
      technologies using these cell lines, including small interfering RNA (siRNA) and
      cDNA transfection, showed that CD5L promoted colony formation and cell
      proliferation and protected against cisplatin-induced apoptosis. To find a
      molecular explanation for these roles, novel CD5L-interacting protein ligands in
      liver cancer cells were identified by immunoprecipitation followed by mass
      spectrometry. Among these, the molecular chaperone of the unfolded protein
      response (UPR), heat shock protein (HSP)-A5, was selected for validation. The
      interaction was confirmed by confocal microscopy in the Huh7 and HepG2 cell
      lines. Furthermore, functional experiments revealed that CD5L activates the UPR
      and autophagy mechanisms in Huh7 cells, thereby providing a novel molecular link
      between the UPR and autophagy in liver cancer.-Aran, G., Sanjurjo, L., Barcena,
      C., Simon-Coma, M., Tellez, E., Vazquez-Vitali, M., Garrido, M., Guerra, L.,
      Diaz, E., Ojanguren, I., Elortza, F., Planas, R., Sala, M., Armengol, C.,
      Sarrias, M.-R. CD5L is upregulated in hepatocellular carcinoma and promotes liver
      cancer cell proliferation and antiapoptotic responses by binding to HSPA5
      (GRP78).

PMID- 29465314
TI  - Endogenously generated arachidonate-derived ligands for TRPV1 induce cardiac
      protection in sepsis.
AB  - The severity of cardiac dysfunction predicts mortality in sepsis. Activation of
      transient receptor potential vanilloid receptor type (TRPV)-1, a predominantly
      neuronal nonselective cation channel, has been shown to improve outcome in sepsis
      and endotoxemia. However, the role of TRPV1 and the identity of its endogenous
      ligands in the cardiac dysfunction caused by sepsis and endotoxemia are unknown.
      Using TRPV1-/- and TRPV1+/+ mice, we showed that endogenous activation of cardiac
      TRPV1 during sepsis is key to limiting the ensuing cardiac dysfunction. Use of
      liquid chromatography-tandem mass spectrometry lipid analysis and selective
      inhibitors of arachidonic metabolism suggest that the arachidonate-derived TRPV1
      activator, 20-hydroxyeicosateraenoic acid (20-HETE), underlies a substantial
      component of TRPV1-mediated cardioprotection in sepsis. Moreover, using selective
      antagonists for neuropeptide receptors, we show that this effect of TRPV1 relates
      to the activity of neuronally released cardiac calcitonin gene-related peptide
      (CGRP) and that, accordingly, administration of CGRP can rescue cardiac
      dysfunction in severe endotoxemia. In sum activation of TRPV1 by 20-HETE leads to
      the release of CGRP, which protects the heart against the cardiac dysfunction in
      endotoxemia and identifies both TRPV1 and CGRP receptors as potential therapeutic
      targets in endotoxemia.-Chen, J., Hamers, A. J. P., Finsterbusch, M., Massimo,
      G., Zafar, M., Corder, R., Colas, R. A., Dalli, J., Thiemermann, C., Ahluwalia,
      A. Endogenously generated arachidonate-derived ligands for TRPV1 induce cardiac
      protection in sepsis.

PMID- 29465315
TI  - Ginsenoside Rh2 inhibits vascular endothelial growth factor-induced corneal
      neovascularization.
AB  - VEGF-induced neovascularization plays a pivotal role in corneal
      neovascularization (CoNV). The current study investigated the potential effect of
      ginsenoside Rh2 (GRh2) on neovascularization. In HUVECs, pretreatment with GRh2
      largely attenuated VEGF-induced cell proliferation, migration, and vessel-like
      tube formation in vitro. At the molecular level, GRh2 disrupted VEGF-induced VEGF
      receptor 2 (VEGFR2)-Grb-2-associated binder 1 (Gab1) association in HUVECs,
      causing inactivation of downstream AKT and ERK signaling. Gab1 knockdown (by
      targeted short hairpin RNA) similarly inhibited HUVEC proliferation and
      migration. Notably, GRh2 was ineffective against VEGF in Gab1-silenced HUVECs. In
      a mouse cornea alkali burn model, GRh2 eyedrops inhibited alkali-induced
      neovascularization and inflammatory cell infiltrations in the cornea.
      Furthermore, alkali-induced corneal expression of mRNAs/long noncoding RNAs in
      cornea were largely attenuated by GRh2. Overall, GRh2 inhibits VEGF-induced
      angiogenic effect via inhibiting VEGFR2-Gab1 signaling in vitro. It also
      alleviates angiogenic and inflammatory responses in alkali burn-treated mouse
      corneas.-Zhang, X.-P., Li, K.-R., Yu, Q., Yao, M.-D., Ge, H.-M., Li, X.-M.,
      Jiang, Q., Yao, J., Cao, C. Ginsenoside Rh2 inhibits vascular endothelial growth
      factor-induced corneal neovascularization.

PMID- 29465316
TI  - Orbital invasion routes of non-melanoma skin cancers and survival outcomes.
AB  - PURPOSE/OBJECTIVES: Overall non-melanoma head and neck skin cancer has a good
      prognosis; however, rarely patients have an aggressive variant which results in
      orbital invasion via perineural spread or direct extension. Despite these
      consequences, there are limited published studies defining this clinical entity.
      The main objectives of the current study are to describe orbital invasion
      patterns of non-melanoma head and neck skin cancers and their impact on survival.
      METHODS: Retrospective case series from a tertiary-care, academic institution
      performed between 2004 and 2014. Demographic and tumour characteristics are
      reported as well as patterns of orbital invasion, types of treatments received,
      and survival outcomes. RESULTS: There were 17 consecutive patients with non
      melanoma skin cancer and orbital invasion who met inclusion criteria. Average age
      at orbital invasion diagnosis was 70.8 years old. 76% were male. Mean follow-up
      time was 28.5 months. Of these patients, 71% had squamous cell carcinoma and 29%
      had basal cell carcinoma. Brow (41%) was the most common primary sub-site
      followed by cheek (23%) and temple (12%). 76% of patients had a history of prior
      treatment. The lateral orbital wall (41%) was the most common site of invasion,
      followed by the medial orbital wall (29%) and antero-superior invasion (23%).
      Age, histology, and location of orbital invasion were associated with disease
      specific and overall survival. CONCLUSION: Orbital invasion for non-melanoma head
      and neck skin cancers creates a treatment dilemma and the patterns of invasion
      are described. In addition, the location of orbital invasion is associated with
      survival outcomes.

PMID- 29465317
TI  - Neuroprotective effects of silibinin: an in silico and in vitro study.
AB  - AIM OF THE STUDY: Astrogliosis is a key contributor for many neurological
      disorders involving apoptosis, neuroinflammation and subsequent neuronal death.
      Silibinin, a polyphenol isolated from milk thistle (Silybum marianum), has been
      shown to suppress the astrocyte activation in various neurodegenerative disorders
      and also exhibit a neuroprotective role in neuroinflammation-driven oxidative
      damage. The present study was designed with an aim to investigate the
      neuroprotective effects of Silibinin against LPS induced oxido-inflammatory
      cascade and astrocyte activation. MATERIALS AND METHODS: We have used in-silico
      molecular modelling techniques to study the interaction and binding affinity of
      silibinin with chemokine receptors associated with neuroinflammation. We have
      also tested silibinin against LPS induced oxido-inflammatory cascade and
      astrocyte activation in C6 glia cell lines. RESULTS: In the present study, we
      found that treatment with silibinin significantly attenuates LPS-oxidative
      nitrosative stress in C6 astrocytoma cells. We also observed the significant
      inhibition of induced astrocyte activity after treatment with silibinin.
      Moreover, molecular modelling studies have proposed a binding pose of silibinin
      with binding sites of p38 MAPK, CX3CR1 and P2X4 which is an important downstream
      cascade involved in glia cell activation and neuroinflammation. CONCLUSIONS:
      Overall, the findings from the current study suggests that silibinin exhibits
      neuroprotective activity by attenuating oxidative damage and astrocytes
      activation.

PMID- 29465318
TI  - Nucleolar stress and sugar response in plants.
AB  - The processes involved in ribosome biogenesis, including synthesis of ribosomal
      proteins, ribosome biogenesis-related factors, and ribosomal RNAs (rRNAs), must
      be coordinately orchestrated in response to changes in energy supply. In animal
      cells, defects in ribosome biogenesis induce a nucleolar stress response through
      the p53-mediated pathway. Our recent finding that an essential, sugar-inducible
      Arabidopsis gene, APUM24, encoded a pre-rRNA processing factor allowed the
      relationships between rRNA biogenesis, nucleolar stress, sugar response, and
      growth regulation to be understood in plants. A knockdown mutant of APUM24
      developed sugar-dependent phenotypes including pre-rRNA processing defects,
      reductions in nucleolar size, and limited promotion of leaf and root growth.
      Alongside the absence of plant p53 homologs and the synchronous sugar-induced
      expression of ribosome biogenesis-related genes, these findings suggest the
      following hypothesis. Sugar supply may enhance ribosome biogenesis defects,
      leading to p53-independent induction of nucleolar stress responses that include
      negative regulation of growth and development in plants.

PMID- 29465319
TI  - Sit Still and Pay Attention! Trunk Movement and Attentional Resources in Infants
      with Typical and Delayed Development.
AB  - AIMS: (1) examine infant movement during an early posture (sitting) utilizing a
      novel video assessment technique; and (2) document the differences between
      infants with typical development (TD), premature infants with motor delay, and
      infants with cerebral palsy (CP) during focused and nonfocused attention (NFA).
      METHODS: Infants were tested when they began to sit independently. We utilized
      Eulerian Video Magnification (EVM) to accentuate small trunk and pelvic movements
      for visual coding from video taken during a natural play task with and without
      focused attention (FA). RESULTS: Trunk/pelvic movement varied as a function of
      both motor skill and attention. Infants with TD and CP made fewer trunk movements
      during periods of FA than NFA. Preterm infants exhibited more trunk/pelvic
      movement than the other groups and their movement did not differ based on
      attention type. CONCLUSIONS: The EVM technique allowed for replicable coding of
      real-time "hidden" motor adjustments from video. The capacity to minimize
      extraneous movements in infants, or "sitting still" may allow greater attention
      to the task at hand, similar to older children and adults. Premature infants'
      excessive trunk/pelvic movement that did not adapt to task requirements could, in
      the long term, impact tasks requiring attentional resources.

PMID- 29465320
TI  - Word Ban? Wherefore "Vulnerable".

PMID- 29465321
TI  - Dynamics of fixational eye position and microsaccades during spatial cueing: the
      case of express microsaccades.
AB  - Microsaccades are systematically modulated by peripheral spatial cues, and these
      eye movements have been implicated in perceptual and motor performance changes in
      cueing tasks. However, an additional oculomotor factor that may also influence
      performance in these tasks, fixational eye position itself, has been largely
      neglected so far. Using precise eye tracking and real-time retinal-image
      stabilization, we carefully analyzed fixational eye position dynamics and related
      them to microsaccade generation during spatial cueing. As expected, during
      baseline fixation, microsaccades corrected for a foveal motor error away from the
      preferred retinal locus of fixation (the so-called ocular position "set point" of
      the oculomotor system). However, we found that this relationship was violated
      during a short period immediately after cue onset; a subset of cue-directed
      "express microsaccades" that were highly precise in time and direction, and that
      were larger than regular microsaccades, occurred. These movements, having <100-ms
      latencies from cue onset, were triggered when fixational eye position was already
      at the oculomotor set point when the cue appeared; they were thus error
      increasing rather than error-decreasing. Critically, even when no microsaccades
      occurred, fixational eye position itself was systematically deviated toward the
      cue, again with ~100-ms latency, suggesting that the oculomotor system
      establishes a new set point at different postcue times. This new set point later
      switched to being away from the cue after ~200-300 ms. Because eye position
      alters the location of retinal images, our results suggest that both eye position
      and microsaccades can be associated with performance changes in spatial cueing
      tasks. NEW & NOTEWORTHY Covert spatial cueing tasks are a workhorse for studying
      cognitive processing in humans and monkeys, but gaze is not perfectly stable
      during these tasks. We found that minute fixational eye position changes,
      independent of the more studied microsaccades, are not random in cueing tasks and
      are thus not "averaged out" in analyses. These changes can additionally dictate
      microsaccade times. Thus, in addition to microsaccadic influences, retinal image
      changes associated with fixational eye position are relevant for performance in
      cueing tasks.

PMID- 29465322
TI  - Learned rather than online relative weighting of visual-proprioceptive sensory
      cues.
AB  - When reaching to an object, information about the target location as well as the
      initial hand position is required to program the motor plan for the arm. The
      initial hand position can be determined by proprioceptive information as well as
      visual information, if available. Bayes-optimal integration posits that we
      utilize all information available, with greater weighting on the sense that is
      more reliable, thus generally weighting visual information more than the usually
      less reliable proprioceptive information. The criterion by which information is
      weighted has not been explicitly investigated; it has been assumed that the
      weights are based on task- and effector-dependent sensory reliability requiring
      an explicit neuronal representation of variability. However, the weights could
      also be determined implicitly through learned modality-specific integration
      weights and not on effector-dependent reliability. While the former hypothesis
      predicts different proprioceptive weights for left and right hands, e.g., due to
      different reliabilities of dominant vs. nondominant hand proprioception, we would
      expect the same integration weights if the latter hypothesis was true. We found
      that the proprioceptive weights for the left and right hands were extremely
      consistent regardless of differences in sensory variability for the two hands as
      measured in two separate complementary tasks. Thus we propose that proprioceptive
      weights during reaching are learned across both hands, with high interindividual
      range but independent of each hand's specific proprioceptive variability. NEW &
      NOTEWORTHY How visual and proprioceptive information about the hand are
      integrated to plan a reaching movement is still debated. The goal of this study
      was to clarify how the weights assigned to vision and proprioception during
      multisensory integration are determined. We found evidence that the integration
      weights are modality specific rather than based on the sensory reliabilities of
      the effectors.

PMID- 29465323
TI  - Peripheral u-opioid receptors attenuate the responses of group III and IV
      afferents to contraction in rats with simulated peripheral artery disease.
AB  - Patients with peripheral artery disease show an exaggerated pressor response to
      mild exercise, an effect attributable to the exercise pressor reflex, whose
      afferent arm comprises the thinly myelinated group III and unmyelinated group IV
      afferents. Previously, we found that DAMGO, a u-opioid agonist injected into the
      femoral artery, attenuated the exaggerated exercise pressor reflex in rats with
      ligated femoral arteries, a preparation that simulates the blood flow patterns to
      muscle that is seen in patients with peripheral artery disease. Continuing this
      line of investigation, we recorded the responses of group III and IV afferents to
      static contraction before and after injecting DAMGO (1 ug) into the superficial
      epigastric artery in rats with patent femoral arteries and in rats with ligated
      femoral arteries. In rats with patent arteries, DAMGO did not change the
      responses to contraction of either group III ( n = 9; P = 0.83) or group IV ( n =
      8; P = 0.34) afferents. In contrast, in rats with ligated femoral arteries, DAMGO
      injection (1 ug) significantly decreased the responses to contraction of both
      group III afferents ( n = 9, P < 0.01) and group IV afferents ( n = 9; P < 0.01).
      DAMGO did not significantly attenuate the responses of either group III or IV
      afferents to capsaicin in rats with either patent or ligated femoral arteries.
      These findings are in agreement with our previous studies that showed that
      peripheral DAMGO injection attenuated the exercise pressor reflex in rats with
      ligated femoral arteries but had only a modest effect on the exercise pressor
      reflex in rats with patent femoral arteries. NEW & NOTEWORTHY In an animal model
      of peripheral artery disease, we show that the u-opioid agonist, DAMGO reduces
      the afferent response rate resulting from stimulated static contraction. These
      results suggest that peripherally active opioid agonists that do not cross the
      blood-brain barrier may be therapeutic for treatment of peripheral artery disease
      without the negative and addictive side effects associated with opioids in the
      central nervous system.

PMID- 29465324
TI  - May the power be with you: are there highly powered studies in neuroscience, and
      how can we get more of them?
AB  - Statistical power is essential for robust science and replicability, but a meta
      analysis by Button et al. in 2013 diagnosed a "power failure" for neuroscience.
      In contrast, Nord et al. ( J Neurosci 37: 8051-8061, 2017) reanalyzed these data
      and suggested that some studies feature high power. We illustrate how publication
      and researcher bias might have inflated power estimates, and review recently
      introduced techniques that can improve analysis pipelines and increase power in
      neuroscience studies.

PMID- 29465325
TI  - Ultra-fast accurate reconstruction of spiking activity from calcium imaging data.
AB  - Calcium imaging provides an indirect observation of the underlying neural
      dynamics and enables the functional analysis of neuronal populations. However,
      the recorded fluorescence traces are temporally smeared, thus making the
      reconstruction of exact spiking activity challenging. Most of the established
      methods to tackle this issue are limited in dealing with issues such as the
      variability in the kinetics of fluorescence transients, fast processing of long
      term data, high firing rates, and measurement noise. We propose a novel,
      heuristic reconstruction method to overcome these limitations. By using both
      synthetic and experimental data, we demonstrate the four main features of this
      method: 1) it accurately reconstructs both isolated spikes and within-burst
      spikes, and the spike count per fluorescence transient, from a given noisy
      fluorescence trace; 2) it performs the reconstruction of a trace extracted from
      1,000,000 frames in less than 2 s; 3) it adapts to transients with different rise
      and decay kinetics or amplitudes, both within and across single neurons; and 4)
      it has only one key parameter, which we will show can be set in a nearly
      automatic way to an approximately optimal value. Furthermore, we demonstrate the
      ability of the method to effectively correct for fast and rather complex, slowly
      varying drifts as frequently observed in in vivo data. NEW & NOTEWORTHY
      Reconstruction of spiking activities from calcium imaging data remains
      challenging. Most of the established reconstruction methods not only have
      limitations in adapting to systematic variations in the data and fast processing
      of large amounts of data, but their results also depend on the user's experience.
      To overcome these limitations, we present a novel, heuristic model-free-type
      method that enables an ultra-fast, accurate, near-automatic reconstruction from
      data recorded under a wide range of experimental conditions.

PMID- 29465327
TI  - Improving the translational potential of rodent models to study the behavioral
      and pathophysiological effects of repetitive mild traumatic brain injury.
AB  - Chronic traumatic encephalopathy (CTE) is thought to be caused by repetitive head
      impacts. Consequently, there is a need to develop rodent models to better
      understand the behavioral and pathophysiological changes of repetitive mild
      traumatic brain injury (rmTBI) and to determine the link between rmTBI and CTE.
      This Neuro Forum article reviews recent rodent rmTBI models, comparing the impact
      methods and outcome measures in terms of translational potential.

PMID- 29465328
TI  - Mechano- and thermosensitivity of injured muscle afferents 20 to 80 days after
      nerve injury.
AB  - Chronic injury of limb nerves leading to neuropathic pain affects deep somatic
      nerves. Here the functional properties of injured afferent fibers in the lateral
      gastrocnemius-soleus nerve were investigated 20 and 80 days after suturing the
      central stump of this muscle nerve to the distal stump of the sural nerve in
      anesthetized rats. Neurophysiological recordings were made from afferent axons
      identified in either the sciatic nerve (87 A-, 63 C-fibers) or the dorsal root
      L4/L5 (52 A-, 26 C-fibers) by electrical stimulation of the injured nerve. About
      70% of the functionally identified A-fibers had regenerated into skin by 80 days
      after nerve suture; the remaining A-fibers could be activated only from the
      injured nerve. In contrast, 93% of the functionally identified C-fibers could
      only be activated from the injured sural nerve after 80 days. Nearly half of the
      injured A- (45%) and C-fibers (44%) exhibited ongoing and/or mechanically or
      thermally evoked activity. Because ~50% of the A- and C-fibers are somatomotor or
      sympathetic postganglionic axons, respectively, probably all injured muscle
      afferent A- and C-fibers developed ectopic activity. Ongoing activity was present
      in 17% of the A- and 46% of the C-fibers. Mechanosensitivity was present in most
      injured A- (99%) and C-fibers (85%), whereas thermosensitivity was more common in
      C-fibers (cold 46%, heat 47%) than in A-fibers (cold 18%, heat 12%). Practically
      all thermosensitive A-fibers and C-fibers were also mechanosensitive. Thus,
      unlike cutaneous axons, almost all A- and C-fibers afferents in injured muscle
      nerves demonstrate ectopic activity, even chronically after nerve injury. NEW &
      NOTEWORTHY After chronic injury of a muscle nerve, allowing the nerve fibers to
      regenerate to the target tissue, 1) most afferent A-fibers are mechanosensitive
      and regenerate to the target tissue; 2) ectopic ongoing activity, cold
      sensitivity, and heat sensitivity significantly decrease with time after injury
      in A-afferents; 3) most afferent C-fibers do not regenerate to the target tissue;
      and 4) injured C-afferents maintain the patterns of ectopic discharge properties
      they already show soon after nerve injury.

PMID- 29465326
TI  - Corrective response times in a coordinated eye-head-arm countermanding task.
AB  - Inhibition of motor responses has been described as a race between two competing
      decision processes of motor initiation and inhibition, which manifest as the
      reaction time (RT) and the stop signal reaction time (SSRT); in the case where
      motor initiation wins out over inhibition, an erroneous movement occurs that
      usually needs to be corrected, leading to corrective response times (CRTs). Here
      we used a combined eye-head-arm movement countermanding task to investigate the
      mechanisms governing multiple effector coordination and the timing of corrective
      responses. We found a high degree of correlation between effector response times
      for RT, SSRT, and CRT, suggesting that decision processes are strongly dependent
      across effectors. To gain further insight into the mechanisms underlying CRTs, we
      tested multiple models to describe the distribution of RTs, SSRTs, and CRTs. The
      best-ranked model (according to 3 information criteria) extends the LATER race
      model governing RTs and SSRTs, whereby a second motor initiation process triggers
      the corrective response (CRT) only after the inhibition process completes in an
      expedited fashion. Our model suggests that the neural processing underpinning a
      failed decision has a residual effect on subsequent actions. NEW & NOTEWORTHY
      Failure to inhibit erroneous movements typically results in corrective movements.
      For coordinated eye-head-hand movements we show that corrective movements are
      only initiated after the erroneous movement cancellation signal has reached a
      decision threshold in an accelerated fashion.

PMID- 29465329
TI  - Time course of ongoing activity during neuritis and following axonal transport
      disruption.
AB  - Local nerve inflammation (neuritis) leads to ongoing activity and axonal
      mechanical sensitivity (AMS) along intact nociceptor axons and disrupts axonal
      transport. This phenomenon forms the most feasible cause of radiating pain, such
      as sciatica. We have previously shown that axonal transport disruption without
      inflammation or degeneration also leads to AMS but does not cause ongoing
      activity at the time point when AMS occurs, despite causing cutaneous
      hypersensitivity. However, there have been no systematic studies of ongoing
      activity during neuritis or noninflammatory axonal transport disruption. In this
      study, we present the time course of ongoing activity from primary sensory
      neurons following neuritis and vinblastine-induced axonal transport disruption.
      Whereas 24% of C/slow Adelta-fiber neurons had ongoing activity during neuritis,
      few (<10%) A- and C-fiber neurons showed ongoing activity 1-15 days following
      vinblastine treatment. In contrast, AMS increased transiently at the vinblastine
      treatment site, peaking on days 4-5 (28% of C/slow Adelta-fiber neurons) and
      resolved by day 15. Conduction velocities were slowed in all groups. In summary,
      the disruption of axonal transport without inflammation does not lead to ongoing
      activity in sensory neurons, including nociceptors, but does cause a rapid and
      transient development of AMS. Because it is proposed that AMS underlies
      mechanically induced radiating pain, and a transient disruption of axonal
      transport (as previously reported) leads to transient AMS, it follows that
      processes that disrupt axonal transport, such as neuritis, must persist to
      maintain AMS and the associated symptoms. NEW & NOTEWORTHY Many patients with
      radiating pain lack signs of nerve injury on clinical examination but may have
      neuritis, which disrupts axonal transport. We have shown that axonal transport
      disruption does not induce ongoing activity in primary sensory neurons but does
      cause transient axonal mechanical sensitivity. The present data complete a
      profile of key axonal sensitivities following axonal transport disruption.
      Collectively, this profile supports that an active peripheral process is
      necessary for maintained axonal sensitivities.

PMID- 29465330
TI  - Spatial bias in estimating the position of visual and proprioceptive targets.
AB  - When people match an unseen hand to a visual or proprioceptive target, they make
      both variable and systematic (bias) errors. Variance is a well-established factor
      in behavior, but the origin and implications of bias, and its connection to
      variance, are poorly understood. Eighty healthy adults matched their unseen right
      index finger to proprioceptive (left index finger) and visual targets with no
      performance feedback. We asked whether matching bias was related to target
      modality and to the magnitude or spatial properties of matching variance. Bias
      errors were affected by target modality, with subjects estimating visual and
      proprioceptive targets 20 mm apart. We found three pieces of evidence to suggest
      a connection between bias and variable errors: 1) for most subjects, the target
      modality that yielded greater spatial bias was also estimated with greater
      variance; 2) magnitudes of matching bias and variance were somewhat correlated
      for each target modality ( R = 0.24 and 0.29); and 3) bias direction was closely
      related to the angle of the major axis of the confidence ellipse ( R = 0.60 and
      0.63). However, whereas variance was significantly correlated with visuo
      proprioceptive weighting as predicted by multisensory integration theory ( R = 
      0.29 and 0.27 for visual and proprioceptive variance, respectively), bias was
      not. In a second session, subjects improved their matching variance, but not
      bias, for both target modalities, indicating a difference in stability. Taken
      together, these results suggest bias and variance are related only in some
      respects, which should be considered in the study of multisensory behavior. NEW &
      NOTEWORTHY People matching visual or proprioceptive targets make both variable
      and systematic (bias) errors. Multisensory integration is thought to minimize
      variance, but if the less variable modality has more bias, behavioral accuracy
      will decrease. Our data set suggests this is unusual. However, although bias and
      variable errors were spatially related, they differed in both stability and
      correlation with multisensory weighting. This suggests the bias-variance
      relationship is not straightforward, and both should be considered in
      multisensory behavior.

PMID- 29465331
TI  - The effect of dimerization on the interaction of ibuprofen drug with calf thymus
      DNA: Molecularmodeling and spectroscopic investigation.
AB  - The interaction between the dimer structure of ibuprofen drug (D-IB) and calf
      thymus DNA under simulative physiological conditions was investigated with the
      use of Hoechst 33258 and methylene blue dye as spectral probes by the methods of
      UV-visible absorption, fluorescence spectroscopy, circular dichroism spectroscopy
      and molecular modeling study.Using the Job's plot, a single class of binding
      sites for theD-IB on DNA was put in evidence. The Stern-Volmer analysis of
      fluorescence quenching data shows the presence of both the static and dynamic
      quenching mechanisms. The binding constants, Kb were calculated at different
      temperatures, and the thermodynamic parameters ?G?, ?H? and ?S? were given. The
      experimental results showed that D-IB molecules could bind with DNA via groove
      binding mode as evidenced by: I. DNA binding constant from spectrophotometric
      studies of the interaction of D-IB with DNA is comparable to groove binding
      drugs. II. Competitive fluorimetric studies with Hoechst 33258 have shown that D
      IB exhibits the ability of this complex to displace with DNA-bounded Hoechst,
      indicating that it binds to DNA in strong competition with Hoechst for the groove
      binding. III. There is no significantly change in the absorption of the MB-DNA
      system upon adding the D-IB, indicates that MB molecules are not released from
      the DNA helix after addition of the D-IB and are indicative of a non
      intercalative mode of binding. IV. Small changes in DNA viscosity in the presence
      of D-IB, indicating weak link to DNA, which is consistent with DNA groove
      binding. As well as, induced CD spectral changes, and the docking results
      revealed that groove mechanism is followed by D-IB to bind with DNA.

PMID- 29465332
TI  - A coaches' perspective on the contribution of anthropometry, physical
      performance, and motor coordination in racquet sports.
AB  - Differences and similarities between table tennis and other racquet sports exist,
      but are not well documented in the literature, in spite of the relevance for
      talent identification. In this study we aimed at identifying the key
      characteristics of table tennis in comparison with tennis and badminton based
      upon a survey in coaches. A total of 177 licensed coaches from all across the
      world and with diverse professional backgrounds completed a survey on
      anthropometric measures, physical performance, and motor coordination skills. On
      a scale from 1 to 10, coaches indicated to what extent a talent characteristic
      was important for their sport. MANOVA identified key differences as well as
      similarities between all three racquet sports and a subsequent discriminant
      analysis allocated coaches correctly for table tennis, tennis, and badminton
      81.01%, 55.6%, and 71.4% respectively. Our results show that table tennis and
      other racquet sport coaches are well aware of differences between the racquet
      sports and also the importance and value of testing and assortment of skill
      components. These findings can assist coaches in future talent orientation and
      transfer in racquet sports.

PMID- 29465333
TI  - US Fine-Needle Aspiration Biopsy for Thyroid Malignancy: Diagnostic Performance
      of Seven Society Guidelines Applied to 2000 Thyroid Nodules.
AB  - Purpose To compare the diagnostic performance of ultrasonography (US)-based fine
      needle aspiration biopsy (FNAB) criteria from seven international societies in
      the detection of thyroid malignancy. Materials and Methods This study included a
      total of 2000 consecutive thyroid nodules (>=1 cm) in 1802 patients with final
      diagnoses from January 2010 to May 2011. US features of the thyroid nodules were
      retrospectively reviewed and were classified according to the categories defined
      by the seven international society guidelines. The diagnostic performance of US
      based FNAB criteria in the detection of thyroid malignancy and unnecessary FNAB
      rates were calculated and compared by using a generalized estimating equation
      method. Results Of the 2000 thyroid nodules, 1546 (78.3%) were benign and 454
      (22.7%) were malignant, with papillary carcinoma comprising 85.5% of all
      malignancies. The Korean Thyroid Association/Korean Society of Thyroid Radiology
      (KTA/KSThR) (94.5%), National Comprehensive Cancer Network (NCCN) (92.5%), and
      American Thyroid Association (ATA) (89.6%) guidelines were more sensitive than
      those of the American Association of Clinical Endocrinologists/American College
      of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME) (80.4%),
      American College of Radiology (ACR) (74.7%), French Society of Endocrinology
      (FSE) (72.7%), and Society of Radiology in Ultrasound (SRU) (70.9%) (P < .001),
      while the latter guidelines had higher specificity (P < .001). The rate of
      unnecessary FNAB was lowest with the ACR guidelines (25.3%), followed by the FSE
      (29.1%), AACE/ACE/AME (32.5%), SRU (45.2%), ATA (51.7%), NCCN (54.0%), and
      KTA/KSThR (56.9%) guidelines. Conclusion Because the diagnostic performance of US
      based FNAB criteria varies according to the individual international society
      guidelines, clinicians should be aware of the strengths and weaknesses of US
      based FNAB criteria in the management of thyroid nodules. (c) RSNA, 2018 Online
      supplemental material is available for this article.

PMID- 29465334
TI  - Association of Mucoid Degeneration of the Anterior Cruciate Ligament at MR
      Imaging with Medial Tibiofemoral Osteoarthritis Progression at Radiography: Data
      from the Osteoarthritis Initiative.
AB  - Purpose To determine whether anterior cruciate ligament (ACL) mucoid degeneration
      in participants with or at risk for osteoarthritis is associated with
      longitudinal risk of radiographic progression of medial tibiofemoral compartment
      joint space loss (JSL). Materials and Methods Baseline demographic, clinical,
      radiographic, and Magnetic Resonance (MR) Imaging Osteoarthritis Knee Score
      (MOAKS) data were evaluated in 600 participants from the Osteoarthritis
      Initiative database. Two blinded musculoskeletal radiologists independently
      evaluated baseline MR images for ACL mucoid degeneration. Multiple logistic
      regression was used to investigate the association between ACL mucoid
      degeneration at MR imaging and JSL progression at radiography, defined as a
      minimum joint space width decrease greater than 0.7 mm (48 months; cutoff
      according to mean and standard deviation of 1-year minimum joint space width
      changes in 90 knees of reference group). Stratified analysis was performed based
      on baseline cartilage surface damage. Results Knees with ACL mucoid degeneration
      showed a greater proportion of JSL progression compared with knees with a normal
      ACL (64% vs 47%; P = .004). After adjustment for all demographic, clinical,
      radiographic, and MOAKS variables, ACL mucoid degeneration was not statistically
      significantly associated with JSL progression in the entire cohort (adjusted odds
      ratio, 1.66; 95% confidence interval: 1.00, 2.77; P = .051). In subgroup
      analysis, ACL mucoid degeneration was statistically significantly associated with
      JSL progression in participants with less baseline cartilage surface damage
      (maximum cartilage surface loss of <=75% in all subregions [P = .015] and <=4 of
      involved subregions with cartilage surface loss [P = .028]). Conclusion ACL
      mucoid degeneration in participants with or at risk for osteoarthritis is
      associated with progression of medial tibiofemoral compartment JSL in knees with
      less baseline cartilage surface area damage. (c) RSNA, 2018 Online supplemental
      material is available for this article.

PMID- 29465335
TI  - Fourteen-month-olds' sensitivity to acoustic salience in minimal pair word
      learning.
AB  - During the first two years of life, infants concurrently refine native-language
      speech categories and word learning skills. However, in the Switch Task, 14-month
      olds do not detect minimal contrasts in a novel object-word pairing (Stager &
      Werker, 1997). We investigate whether presenting infants with acoustically
      salient contrasts (liquids) facilitates success in the Switch Task. The first two
      experiments demonstrate that acoustic differences boost infants' detection of
      contrasts. However, infants cannot detect the contrast when the segments are
      digitally shortened. Thus, not all minimal contrasts are equally difficult, and
      the acoustic properties of a contrast matter in word learning.

PMID- 29465336
TI  - Current Emergency Preparedness Resources and Capabilities Among Academic Health
      Systems in the United States.
AB  - OBJECTIVE: Although hospital emergency preparedness efforts have been recognized
      as important, there has been growing pressure on cost containment, as well as
      consolidation within the US health care system. There is little data looking at
      what health care emergency preparedness functions have been, could be, or should
      be centrally coordinated at a system level. METHODS: We developed a questionnaire
      for academic health systems and asked about program funding, resources provided,
      governance, and activities. The questionnaire also queried managers' opinions
      regarding the appropriate role for the system-level resources in emergency
      response, as well as about what is most helpful at the system-level supporting
      preparedness. RESULTS: Fifty-two of 97 systems (54%) responded. The most
      frequently occurring system-wide activities included: creating trainings or
      exercise templates (75%), promoting preparedness for employees in the system
      (75%), providing access to specific subject matter experts (73%), and developing
      specific plans for individual member entities within their system (73%). The top
      resources provided included a common mass notification system (71%), arranging
      for centralized contracts for goods and services (71%), and providing subject
      matter expertise (69%). CONCLUSIONS: Currently, there is wide variation in the
      resources, capabilities, and programs used to support and coordinate system-level
      emergency preparedness among academic health systems. (Disaster Med Public Health
      Preparedness. 2018;12:574-577).

PMID- 29465337
TI  - Jatrophihabitans telluris sp. nov., isolated from sediment soil of lava forest
      wetlands and the emended description of the genus Jatrophihabitans.
AB  - A novel actinobacterial strain, designated N237T, was isolated from sediment soil
      of wetlands at Meonmulkkak, Dongbaek-Dongsan, the lava forest, Gotjawal, Jeju,
      Republic of Korea. Cells of strain N237T were Gram-stain-positive, non-motile
      rods and formed pale yellow colonies on ten-fold diluted Reasoner's 2A agar.
      Strain N237T contained iso-C16 : 0 and C17 : 1omega8c as the major fatty acids,
      MK-9(H4) as the predominant isoprenoid quinone and meso-DAP as the diamino acid
      in the peptidoglycan. It contained diphosphatidylglycerol, phosphatidylinositol
      polymannosides, an unidentified phospholipid, an unidentified aminophospholipid,
      an unidentified aminolipid, two unidentified glycophospholipids, three
      unidentified glycolipids and two unidentified lipids as polar lipids. The DNA G+C
      content was 68.1 mol%. Strain N237T formed a separate lineage in the genus
      Jatrophihabitans, as demonstrated by phylogenetic analysis based on 16S rRNA
      sequencing. It was most closely related to Jatrophihabitans soli KIS75-12T (95.6
      % sequence similarity). The combined phenotypic, chemotaxonomic and phylogenetic
      characteristics supported the conclusion that strain N237T represents a novel
      species in the genus Jatrophihabitans, for which the name Jatrophihabitans
      telluris sp. nov. is proposed. The type strain is N237T (=KCTC 39922T=NRRL B
      65477T).

PMID- 29465338
TI  - Virgibacillus phasianinus sp. nov., a halophilic bacterium isolated from faeces
      of a Swinhoe's pheasant, Lophura swinhoii.
AB  - A rod-shaped, Gram-stain-positive, motile and aerobic bacterium, designated
      LM2416T, was isolated from faeces of Lophuras winhoii living in Seoul Grand Park,
      Gyeonggi-do, Republic of Korea. Phylogenetic analyses based on 16S rRNA gene
      sequences indicated that strain LM2416T belonged to the genus Virgibacillus,
      sharing high 16S rRNA gene sequence similarities to Virgibacillus necropolis LMG
      19488T (99.0 %), Virgibacillus carmonensis LMG 20964T (98.4 %), Virgibacillus
      arcticus Hal 1T (98.3 %) and Virgibacillus flavescens S1-20T (97.9 %). The
      isolate grew at 10-30  degrees C, pH 6-7 and 0-20 % (w/v) NaCl. Optimal growth
      was observed at 30  degrees C, pH 6-7 and 10 % (w/v) NaCl. The major fatty acid
      was anteiso-C15 : 0. Polar lipids were composed of phosphatidylglycerol,
      diphosphatidylglycerol, three unknown phospholipids and two unknown
      aminophospholipids. The main menaquinone was MK-7. Strain LM2416T had alanine,
      lysine, glutamic acid, glycine and aspartic acid as cell-wall amino acids and
      ribose as a cell-wall sugar. The whole genome sequences of strain LM2416T and V.
      necropolis KCTC 3820T were sequenced by PacBio RS II sequencing. The genome
      sequence-based G+C content of strain LM2416T was 39.5 mol%. The orthologous
      average nucleotide identity value, showing genetic relatedness between strain
      LM2416T and V. necropolis KCTC 3820T, was 78.3 %. Based on the phylogenetic,
      biochemical, chemotaxonomic and genotypic data presented in this study, strain
      LM2416T is considered to represent a novel species of the genus Virgibacillus,
      for which the name Virgibacillus phasianinus is proposed. The type strain is
      LM2416T (=KCTC 33927T=JCM 32144T).

PMID- 29465339
TI  - Edaphobacter lichenicola sp. nov., a member of the family Acidobacteriaceae from
      lichen-dominated forested tundra.
AB  - An isolate of aerobic, Gram-stain-negative, rod-shaped, non-motile and light-pink
      pigmented bacteria, designated SBC68T, was obtained from slightly decomposed
      thalli of the lichen Cladonia sp. collected from the forested tundra of north
      western Siberia. Cells of this isolate occurred singly, in pairs or in rosettes.
      These bacteria were acidophilic (optimum growth at pH 4.3-5.6) and mesophilic
      (optimum growth at 20-30  degrees C) but were also capable of growth at low
      temperatures, down to 7  degrees C. The preferred growth substrates were sugars,
      some organic acids and lichenan. The major fatty acids were iso-C15 : 0, C16 :
      1omega7c, C16 : 0, C16 : 1omega7t, and 13,16-dimethyl octacosanedioic acid. The
      only quinone was MK-8, and the G+C content of the DNA was 54.7 mol%. SBC68T
      represented a member of the family Acidobactericeae; the closest taxonomically
      described relatives were Edaphobacter dinghuensis DHF9T and Granulicella
      aggregans TPB6028T (97.2 and 97.1 % 16S rRNA gene sequence similarity,
      respectively). In 16S rRNA gene-based trees, SBC68T clustered together with
      species of the genus Edaphobacter. However, this isolate differed from all
      previously described species of the genus Edaphobacter with respect to the pink
      pigmentation, formation of cell rosettes and substrate utilization pattern. On
      the basis of these data, strain SBC68T should be considered to represent a novel
      species of acidobacteria, for which the name Edaphobacterlichenicola sp. nov. is
      proposed. The type strain is SBC68T (=DSM 104462T=VKM B-3208T).

PMID- 29465341
TI  - Microbe Profile: Corynebacterium diphtheriae - an old foe always ready to seize
      opportunity.
AB  - Corynebacterium diphtheriae is a globally important Gram-positive aerobic
      Actinobacterium capable of causing the toxin-mediated disease, diphtheria.
      Diphtheria was a major cause of childhood mortality prior to the introduction of
      the toxoid vaccine, yet it is capable of rapid resurgence following the breakdown
      of healthcare provision, vaccination or displacement of people. The mechanism and
      treatment of toxin-mediated disease is well understood, however there are key
      gaps in our knowledge on the basic biology of C. diphtheriae particularly
      relating to host colonisation, the nature of asymptomatic carriage, population
      genomics and host adaptation.

PMID- 29465340
TI  - Bacillus alkalitolerans sp. nov., isolated from marine sediment near a
      hydrothermal vent.
AB  - A Gram-stain-positive, endospore-forming, rod-shaped, motile and strictly aerobic
      strain, designated T3-209T, was isolated from sediment sampled at a water depth
      of 1206 m of the southern Okinawa Trough at station T1 (25.07 degrees  N, 122.58
      degrees  E) near the Tangyin hydrothermal vent during an expedition on the R/V
      Kexue in May 2014. The strain was able to grow at a temperature range of 10-42 
      degrees C (optimum 28  degrees C). Growth was observed at NaCl concentrations
      (w/v) of 0-6 % (optimum 0 %). The pH range for growth was 7.0-9.0 (optimum 8.0).
      The 16S rRNA gene sequence analysis indicated that strain T3-209T belonged to the
      genus Bacillus within the family Bacillaceae and was most closely related to
      Bacillus drentensis LMG 21831T and Bacillus bataviensis LMG 21833T, with the same
      sequence similarity (97.0 %), but shared relatively low levels of similarity
      (92.6-96.9 %) to the type strains of other Bacillus species. The peptidoglycan
      type of strain T3-209T was meso-diaminopimelic acid. The predominant cellular
      fatty acids were anteiso-C15 : 0, iso-C15 : 0 and alcohol-C16 : 1omega7c. The
      respiratory quinone was menaquinone-7. The polar lipids of strain T3-209T
      comprised phosphatidylglycerol, two unidentified phospholipids and one
      unidentified aminolipid. The DNA G+C content was 41.8 mol%. Combining results of
      phylogenetic analysis, phenotypic characterization and chemotaxonomic studies,
      strain T3-209T represents a novel species of the genus Bacillus, for which the
      name Bacillus alkalitolerans sp. nov. is proposed. The type strain is T3-209T
      (=KCTC 33631T=DSM 29135T=MCCC 1K00503T).

PMID- 29465342
TI  - Lack of glyoxylate shunt dysregulates iron homeostasis in Pseudomonas aeruginosa.
AB  - The aceA and glcB genes, encoding isocitrate lyase (ICL) and malate synthase,
      respectively, are not in an operon in many bacteria, including Pseudomonas
      aeruginosa, unlike in Escherichia coli. Here, we show that expression of aceA in
      P. aeruginosa is specifically upregulated under H2O2-induced oxidative stress and
      under iron-limiting conditions. In contrast, the addition of exogenous redox
      active compounds or antibiotics increases the expression of glcB. The
      transcriptional start sites of aceA under iron-limiting conditions and in the
      presence of iron were found to be identical by 5' RACE. Interestingly, the
      enzymatic activities of ICL and isocitrate dehydrogenase had opposite responses
      under different iron conditions, suggesting that the glyoxylate shunt (GS) might
      be important under iron-limiting conditions. Remarkably, the intracellular iron
      concentration was lower while the iron demand was higher in the GS-activated
      cells growing on acetate compared to cells growing on glucose. Absence of GS
      dysregulated iron homeostasis led to changes in the cellular iron pool, with
      higher intracellular chelatable iron levels. In addition, GS mutants were found
      to have higher cytochrome c oxidase activity on iron-supplemented agar plates of
      minimal media, which promoted the growth of the GS mutants. However, deletion of
      the GS genes resulted in higher sensitivity to a high concentration of H2O2,
      presumably due to iron-mediated killing. In conclusion, the GS system appears to
      be tightly linked to iron homeostasis in the promotion of P. aeruginosa survival
      under oxidative stress.

PMID- 29465344
TI  - Microbe Profile: Mycobacterium tuberculosis: Humanity's deadly microbial foe.
AB  - Mycobacterium tuberculosis is an expert and deadly pathogen, causing the disease
      tuberculosis (TB) in humans. It has several notable features: the ability to
      enter non-replicating states for long periods and cause latent infection;
      metabolic remodelling during chronic infection; a thick, waxy cell wall; slow
      growth rate in culture; and intrinsic drug resistance and antibiotic tolerance.
      As a pathogen, M. tuberculosis has a complex relationship with its host, is able
      to replicate inside macrophages, and expresses diverse immunomodulatory
      molecules. M. tuberculosis currently causes over 1.8 million deaths a year,
      making it the world's most deadly human pathogen.

PMID- 29465343
TI  - Stackebrandtia soli sp. nov., a novel actinobacterium isolated from a soil
      sample.
AB  - An aerobic actinobacterium, strain AN130378T, was isolated from a soil sample
      collected in Korea and subjected to taxonomic investigation using a polyphasic
      approach. Phylogenetic analysis based on 16S rRNA gene sequence data showed that
      strain AN130378T is a member of the genus Stackebrandtia, with sequence
      similarities of 97.3 % to Stackebrandtia albiflava YIM 45751T and 97.1 % to
      Stackebrandtia endophytica YIM 64602T. The whole-cell hydrolysates contained meso
      diaminopimelic acid as the diagnostic diamino acid, and galactose, glucose and
      xylose. The major menaquinones were MK-11(H4), MK-10(H4) and MK-11(H6), while the
      major fatty acids were identified as iso-C15 : 0, anteiso-C17 : 0, anteiso-C15 :
      0, iso-C17 : 0 and summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c). The
      polar lipids were identified as diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylglycerol, phosphatidylmethylethanolamine, an unidentified
      aminophospholipid, four unidentified glycolipids, three unidentified
      phospholipids and two unidentified polar lipids. The G+C content of the genomic
      DNA was determined to be 67.7 mol%. All chemotaxonomic and genotypic data
      indicated that the strain belongs to the genus Stackebrandtia. On the basis of
      morphological, chemotaxonomic data and phylogenetic analysis, strain AN130378T is
      considered to represent a novel species within the genus Stackebrandtia, for
      which the name Stackebrandtia soli sp. nov. is proposed. The type strain is
      AN130378T (=DSM 103573T=KCTC 39809T).

PMID- 29465345
TI  - The group I alphabaculovirus-specific protein, AC5, is a novel component of the
      occlusion body but is not associated with ODVs or the PIF complex.
AB  - Autographa californica nucleopolyhedrovirus (AcMNPV) orf5 (ac5) is a group I
      alphabaculovirus-specific gene of unknown function, although the protein (AC5)
      was previously reported to be associated with the per os infectivity factor (PIF)
      complex. The purpose of this study was to study the dynamics of AC5 during AcMNPV
      infection and to verify whether it is indeed a component of the PIF complex.
      Transcription and expression analyses suggested that ac5 is a late viral gene. An
      ac5-deleted recombinant AcMNPV was generated by homologous recombination. A one
      step growth curve assay indicated that ac5 was not required for budded virus (BV)
      production in Sf9 cells. Scanning electron microscopy and transmission electron
      microscopy demonstrated that the deletion of ac5 did not affect occlusion body
      (OB) morphology, and nor did it affect the insertion of occlusion-derived virus
      (ODV) into OBs. Partially denaturing SDS-PAGE and a co-immunoprecipitation assay
      clearly showed that AC5 was not a component of the PIF complex, while the
      deletion of ac5 did not affect the formation and presence of the PIF complex.
      Further analyses showed, however, that AC5 was an OB-specific protein, but it was
      not detected as a component of BVs or ODVs. Bioassay experiments showed that the
      oral infectivity of ac5-deleted AcMNPV to third instar Spodoptera exigua larvae
      was not significantly different from that of the ac5-repaired virus. In
      conclusion, AC5 is an intrinsic protein of OBs, instead of being a component of
      the PIF complex, and is not essential for either BV or ODV infection. AC5 is
      awaiting the assignment of another hitherto unknown function.

PMID- 29465346
TI  - IL-6 receptor inhibition modulates type III collagen and C-reactive protein
      degradation in rheumatoid arthritis patients with an inadequate response to anti
      tumour necrosis factor therapy: analysis of connective tissue turnover in the
      tocilizumab RADIATE study.
AB  - OBJECTIVES: The objective of this study was to examine the tissue degradation in
      response to anti-IL6 receptor treatment in rheumatoid arthritis (RA) patients
      which are anti-TNF-alpha inadequate responders. METHODS: RADIATE was a
      randomised, double-blinded, placebo-controlled, parallel-group, phase III trial.
      RA patients with previous inadequate response to anti-TNFalpha therapy (n=299)
      were randomly assigned to tocilizumab 4 or 8 mg/kg with methotrexate (10-25 mg
      weekly) or placebo with methotrexate. Type III collagen degradation (C3M) and CRP
      degradation (CRPM) were analysed in serum samples at baseline and 16 weeks.
      RESULTS: Treatment with 4 and 8 mg/kg tocilizumab significantly decreased C3M
      (p=0.0001 and p=0.0007) and CRPM (p<0.0001) levels after 16 weeks. Changes in C3M
      and CRPM levels after 16 weeks correlated well with the changes in disease
      activity score 28 (DAS28). Change in CRPM levels furthermore correlated
      moderately with the change in patient pain (VAS) (rpartial of 0.20) and Health
      assessment questionnaire disability index (HAQ-DI) (rpartial of 0.24). Changes in
      biomarker levels above median change led to an odds ratio of 1.95 (C3M) and 3.00
      (CRPM) for achieving the American College of Rheumatology 20% improvement
      criteria (ACR20). CONCLUSIONS: This study shows that a decrease in inflammation
      leads to a decrease in excessive extracellular matrix degradation. It furthermore
      supports earlier shown evidence that tocilizumab works in the treatment of RA
      patients, although there is a clear need for identifying and selecting patients
      who are more likely to respond to treatment.

PMID- 29465347
TI  - An increased major vessel uptake by 18F-FDG-PET/CT in NIH criteria inactive
      patients with Takayasu's arteritis.
AB  - OBJECTIVES: The commonly adopted method of defining active disease in Takayasu's
      arteritis (TAK) is the definition used by the US National Institutes of Health
      (NIH). A gold standard in imaging techniques for assessing disease activity in
      TAK has not been clearly established and the creation of practical and valid
      tools represents a challenge. To assess whether 18F-FDG-PET/CT and NIH criteria
      show a good level of agreement in assessing disease activity of TAK patients.
      METHODS: 18F-FDG-PET/CT was performed in 17 patients with TAK. All 17 patients
      fulfilled the clinical criteria according to the American College of Rheumatology
      criteria. Two nuclear physicians visually assessed the degree of 18F-FDG uptake
      in the inflammatory vascular lesion. 18F-FDG-PET/CT and the inflammatory vascular
      lesion were evaluated by using the standardised uptake value (SUV) of 18F-FDG
      accumulation were interpreted as active vasculitic lesions. RESULTS: Of the 17
      patients, 6 were in the active stage and 11 were in the inactive stage according
      to the level of disease activity as clinically assessed by the NIH criteria. No
      significant 18F-FDG accumulation was observed in the patients with inactive
      disease (SUV<=1.2). 18F-FDG-PET/CT localised 18F-FDG accumulation in the
      inflammatory lesion in the patients with TAK who had inactive disease (n=3)
      assessed by the NIH criteria. 18F-FDG PET/CT revealed intense 18F-FDG
      accumulation (SUV max 2.88) in the vasculature of 3 patients in the inactive
      stage of TAK. The other 8 patients in the active stage showed weak 18F-FDG
      accumulation (SUV <=1.2). CONCLUSION: 18FDG-PET/CT appears to be a promising
      technique for the diagnosis and assessment of disease activity in patients of
      TAK, even those considered to be inactive by the NIH criteria. However, it needs
      to be validated in larger groups for cost-effectiveness and sensitivity to
      change.

PMID- 29465348
TI  - Increased circulating CD14brightCD16+ intermediate monocytes are regulated by TNF
      alpha and IL-6 axis in accordance with disease activity in patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: Although circulating CD14brightCD16+ monocyte subsets are increased
      in inflammatory disease, the pathogenesis of the increase in the inflammatory
      condition of the cells is still unclear and the relationship to cytokines is
      unknown particularly in rheumatoid arthritis (RA). The purpose of this study was
      to investigate the influence anti-cytokine treatment has on CD14brightCD16+
      monocytes in patients with RA. METHODS: Thirty-two RA patients and 14 healthy
      volunteers (HV) were enrolled in this study. All the patients had never been
      treated with methotrexate (MTX) or biological agents. Peripheral blood samples
      and clinical information of the patients were obtained at the time of 0, 12 and
      24 weeks of treatment. Peripheral blood samples were also obtained from the HV.
      The expression levels of CD14 and CD16 on monocytes were measured by flow
      cytometry (FCM). RESULTS: Eight patients received anti-interleukin (IL)-6
      receptor antibody, tocilizumab (TCZ) treatment alone, 12 patients received anti
      tumour necrosis factor (TNF)-alpha antibody, adalimumab (ADA) with MTX treatment
      and the others received only MTX treatment. FCM analysis revealed that the
      proportion of CD14brightCD16+ monocytes significantly increased in patients at
      baseline compared with HV. The proportion of CD14brightCD16+ monocytes
      significantly decreased after TCZ, and ADA with MTX treatment. The proportion of
      intermediate monocytes was significantly and positively correlated with disease
      activity and it improved in accordance with the proportion of CD14brightCD16+
      monocytes after inhibition of signal transduction of inflammatory cytokines.
      CONCLUSIONS: We showed that the population of CD14brightCD16+ monocytes
      significantly decreased with the change of disease activity by key cytokines, IL
      6 or TNF-alpha signal blockade in RA. This result indicates that the proportion
      of those monocytes is important for reflecting disease activity in RA.

PMID- 29465349
TI  - Association of depression with socioeconomic status, anticardiolipin antibodies,
      and organ damage in patients with systemic lupus erythematosus: results from the
      KORNET registry.
AB  - OBJECTIVES: Depression is more common in patients with systemic lupus
      erythematosus (SLE) compared to the general population. However, few studies have
      investigated risk factors of depression in SLE patients, and the results are
      inconsistent. This study evaluated the prevalence of, and risk factors for,
      depression in ethnically homogeneous Korean SLE patients. METHODS: In this study,
      505 consecutive SLE patients were enrolled from the Korean Lupus Network
      registry. Demographic variables, clinical manifestations, laboratory findings,
      physician global assessment, and SLEDAI-2000 and SLICC damage index were recorded
      at enrolment. Patients were identified as having depressive symptoms using the
      Korean version of the Beck Depression Inventory (BDI) with a cut-off >=16, and
      categorised into four groups. Multivariable logistic regression analyses were
      performed to identify independent risk factors for depression defined as a BDI
      score >=16. RESULTS: Of the 505 patients, 97 (19.2%) were diagnosed with
      depression. Patients with a higher BDI score were older, more likely to be a
      current smoker, and had a SLICC score >1. Conversely, they had lower income and
      educational levels. Regarding the serologic findings, patients with a higher BDI
      score had lower anti-double-stranded DNA positivity and higher anticardiolipin
      (aCL) positivity. On multivariate analysis, the following factors were associated
      with depression: current smoking status (OR 2.533, p=0.049), aCL-positivity (OR
      2.009, p=0.035), and a SLICC damage index score >1 (OR 2.781, p=0.039). On the
      other hand, high-level education (OR 0.253, p=0.024) and a high income (OR 0.228,
      p=0.008) were negatively associated with depression. CONCLUSIONS: Our results
      show that depression is prevalent in patients with SLE and multiple factors are
      associated with depression in SLE. These data could help guide target programmes
      for those at high risk of depression in SLE.

PMID- 29465350
TI  - The association of endothelial nitric oxide synthase gene single nucleotide
      polymorphisms with paediatric systemic lupus erythematosus.
AB  - OBJECTIVES: Endothelial nitric oxide synthase (eNOS) is a type of nitric oxide
      synthase that mainly exists in the endothelium. It produces nitric oxide (NO) to
      regulate the function of endothelial cells. Endothelial dysfunction and increased
      NO metabolites have been shown in animal models of lupus and in lupus patients,
      so eNOS gene polymorphisms may be important in the pathogenesis of SLE. This
      study aimed to investigate the association of the single nucleotide polymorphisms
      (SNPs) of eNOS and paediatric systemic lupus erythematosus (pSLE). METHODS: A
      total of 91 pSLE cases and 90 healthy controls were used in this study. We
      divided these patients into 4 subgroups according to kidney or central nervous
      system involvement. Four selected SNPs in the gene were analysed with MALDI-TOF
      mass spectrometry. Statistical methods were carried out to investigate the
      correlation between the SNPs and pSLE. RESULTS: SNP rs1808593 genotype GT in case
      group were significantly higher than those in the control group (p=0.047), and
      the genotype GT had positive correlation with pSLE (OR=1.93, 95% CI: 1.01-3.69).
      In subgroup C (the patients with central nervous system but no kidney damage),
      the genotype GT was significantly higher than those in the control group
      (p=0.028), and the genotype GT was related to pSLE with central nervous system
      damage (OR=6.24, 95% CI: 1.17-33.15). In male patients, we found SNP rs1808593
      genotype GT in pSLE group was significantly higher than in the control group
      (p=0.0065), and the risk of pSLE increased in patients with genotype GT (OR=8.36,
      95% CI: 2.02-34.6). CONCLUSIONS: SNP rs1808593 GT genotype is significantly
      higher than that in the control group, which may indicate that this genotype
      increases the risk of pSLE, especially in boys, and also this genotype might
      increase the risk of central nervous system involvement. Therefore, eNOS gene SNP
      rs1808593 genotype may have an important role in predicting the occurrence of
      pSLE and central nervous system complications in pSLE.

PMID- 29465351
TI  - Increased remodelling of interstitial collagens and basement membrane is
      suppressed by treatment in patients with rheumatoid arthritis: serological
      evaluation of a one-year prospective study of 149 Japanese patients.
AB  - OBJECTIVES: This prospective study aimed to use serological biomarkers for
      evaluation of, connective tissue turnover, in a population of 149 Japanese
      patients with rheumatoid arthritis (RA). It was aimed to investigate how the
      connective tissue was affected by treatment at follow-up after 1 year (+/- 6
      weeks) with either methotrexate (n=23) alone, or in combination with: adalimumab
      (n=49), tofacitinib (n=27) or tocilizumab (n=50). METHODS: Clinical
      characteristics were collected and connective tissue turnover, was evaluated by 4
      serological biomarkers: C1M and C3M reflect degradation of types I and III
      collagen in interstitial tissue; C4M, reflecting degraded type IV collagen of the
      basement membranes; and CRPM, a marker of degraded C-reactive protein. Evaluated
      biomarker levels were measured at baseline and at follow-up. Levels were compared
      to the reference levels of healthy individuals. RESULTS: The four evaluated
      biomarkers were all elevated at baseline in patients with RA compared to healthy
      individuals. The biomarkers were higher in RA patients compared to healthy
      individuals at baseline and they were all significantly correlated with disease
      activity score of 28 joint (DAS28) (p<0.0001). The biomarker levels were all
      significantly decreased in all four patient groups at follow-up in all of the
      four treatment groups. CONCLUSIONS: Rheumatoid joint inflammation elicits
      enhanced turnover of major collagen constituents of the synovial membrane and
      this abnormal pathway may be implicated in erosive progression. Evaluations of
      the applied biomarkers: C1M, C3M, C4M and CRPM, indicate that the pathologically
      enhanced tissue turnover was attenuated, by all of the four studied treatments.

PMID- 29465352
TI  - Immune response against the coiled coil domain of Sjogren's syndrome associated
      autoantigen Ro52 induces salivary gland dysfunction.
AB  - OBJECTIVES: The structural domains of Ro52, termed the RING, B-box, coiled coil
      (CC) and B30.2/SPRY are targets of anti-Ro52 in multiple autoimmune disorders. In
      Sjogren's syndrome patients, the presence of anti-Ro52 is associated with higher
      disease severity, and in mice, they induce salivary gland hypofunction. This
      study was undertaken to investigate whether immune responses against different
      domains of Ro52, influences salivary gland disease in mice. METHODS: Female
      NZM2758 mice were immunised with Ro52 domains expressed as recombinant fusion
      proteins with maltose binding protein (MBP) [MBP-RING-B-box, MBP-CC, MBP
      CC(DeltaC19), MBP-B30.2/SPRY]. Sera from immunised mice were studied for IgG
      antibodies to Ro52 by immunoprecipitation, and to salivary gland cells by
      immunofluorescence. Pilocarpine-induced saliva production was measured to
      evaluate salivary gland function. Submandibular glands were investigated by
      histopathology for inflammation and by immune-histochemistry for IgG deposition.
      RESULTS: Mice immunised with different Ro52-domains had comparable reactivity to
      Ro52 and to salivary gland cells. However, only mice immunised with the CC domain
      and its C-terminal truncated version CC(DeltaC19) showed a significant drop in
      saliva production. None of the mice developed severe salivary gland inflammation.
      The salivary gland hypofunction significantly correlated with increased intra
      lobar IgG deposits in the submandibular salivary glands. CONCLUSIONS: Our data
      demonstrate that epitope specificity of anti-Ro52 antibodies plays a critical
      role in the induction of glandular dysfunction. Clearly, screening Sjogren's
      syndrome patients for relative levels of Ro52 domain specific antibodies will be
      more informative for associating anti-Ro52 with clinical measures of the
      disorder.

PMID- 29465353
TI  - Serum IgG ACPA-IgM RF immune complexes were detected in rheumatoid arthritis
      patients positive for IgM ACPA.
AB  - OBJECTIVES: Since the presence of IgM antibodies is a hallmark of ongoing immune
      response, we aimed to identify immunologically active rheumatoid arthritis (RA)
      patients by detecting IgM anti-citrullinated protein antibody (ACPA) levels.
      METHODS: IgM ACPA levels were determined in the serum of 176 RA patients by
      enzyme-linked immunosorbent assay, in which parameters of reactivity against
      citrullinated and non-citrullinated peptides were compared to ensure the
      specificity. Influence of IgM rheumatoid factor (RF) on IgM ACPA detection was
      examined by removing IgG, using protein G-conjugated beads, or by purifying ACPA,
      using citrullinated peptide-conjugated beads. RESULTS: Although IgM specific for
      citrullinated proteins was detected in some patients (11%), IgM molecules
      reactive to both citrullinated and non-citrullinated peptides were detected in a
      substantial number of patient samples (12%). IgM ACPA-positive reactions were
      associated with the presence of IgG ACPA and IgM RF. Surprisingly, protein G
      mediated removal of IgG from the serum eliminated positivity for IgM ACPA,
      suggesting that IgG ACPA-IgM RF complex was being detected. This assumption was
      confirmed by the detection of IgM RF in the eluate of protein G beads and
      citrullinated peptide-conjugated beads. CONCLUSIONS: In an attempt to detect IgM
      ACPA, we mostly revealed false positive reactions due to the presence of IgM
      molecules, which were not specific for citrullinated proteins, and IgG ACPA-IgM
      RF immune complex. The latter complex had been proposed to play a role in the
      pathogenesis of RA, and here, for the first time, we have demonstrated its
      presence in the sera of RA patients.

PMID- 29465354
TI  - Self-reported childhood maltreatment, lifelong traumatic events and mental
      disorders in American and Israeli rheumatoid arthritis patients.
AB  - OBJECTIVES: Psychological stress is thought to play a major role in the
      development and exacerbation of autoimmune diseases in general, as well as in
      rheumatoid arthritis (RA) in particular. The aims of the current study are to
      compare retrospective self-reports of childhood maltreatment and lifetime major
      life/traumatic experiences of American and Israeli RA patients, using
      standardised instruments, while adjusting for concomitant mental disorders and
      psychological distress, in order to rule out their part in the subjective
      reports, thus addressing the trans-cultural robustness of the association between
      childhood maltreatment, traumatic experiences and RA. METHODS: RA patients at the
      participating study centres were recruited by their physicians, both in Israel
      and the USA. Patients filled out questionnaires regarding demographic data,
      disease activity, psychological distress, potential anxiety and potential
      depression. In addition, patients answered questions regarding pain and childhood
      maltreatment. RESULTS: 83 RA patients were recruited in the US and 23 patients in
      Israel. The comparison of CTQ-subscales between the US and Israeli cohorts showed
      significant differences between the groups only in the subscales of emotional
      neglect (US 10.30+/-5.05, Israeli 22.67+/-3.68, p<0.05) and emotional abuse (US
      10.46+/-5.77, Israeli 7.13+/-4.84, p<0.05). 87% of Israeli patients had severe
      emotional neglect. Severe emotional abuse was associated with probable depression
      (OR 7.778, CI [1.907-31.716]). Using Pain Disability Index (PDI) score, Americans
      reported more pain during sexual activity than Israelis (US PDI Score 5.64+/
      3.70. Israeli 3.16+/-3.86, p<0.05). PDI score was also associated with a previous
      traumatic event (36.89+/-18.57 vs. 16.82+/-14.85, p<0.05). CONCLUSIONS: A high
      degree of similarity was demonstrated between American and Israeli populations of
      RA patients, regarding psychological stressors and previous traumatic events. As
      expected, the results indicated a link between emotional abuse and depression in
      these patients. In addition, a previous traumatic event was associated with more
      significant pain. Physicians caring for RA patients should be vigilant regarding
      the possible association with childhood adversity and should consider appropriate
      consultations when indicated. In addition, while dealing with pain management in
      RA patients, physicians should keep in mind the possible contribution of distant
      childhood adversity.

PMID- 29465355
TI  - Functional characterisation of ADP ribosylation factor-like protein 15 in
      rheumatoid arthritis synovial fibroblasts.
AB  - OBJECTIVES: ARL15 is a novel susceptibility gene identified in a recent GWAS in a
      north Indian rheumatoid arthritis (RA) cohort. However, the role of ARL15 or ARF
      family genes in RA aetiology remains unknown. Therefore, we aimed to i) establish
      the expression of ARL15 in rheumatoid arthritis synovial fibroblasts (RASF) and
      ii) its functional characterisation by assessing its effects on major
      inflammatory cytokines and interacting partners using a knockdown approach.
      METHODS: RASF were cultured from synovial tissue obtained from RA patients (n=5)
      and osteoarthritis (OA) patients (n=3) serving as controls. Expression of ARL15,
      ARF1 and ARF6 in RASF was checked by semi-quantitative PCR and western blots; and
      altered expression of ARL15, if any, by induction of RASF with TNF using real
      time PCR. The effect of ARL15 on the expression of adiponectin, adiponectin
      receptor I, IL6 and GAPDH and on cell mobility by invasion and migration assays
      were assessed by siRNA mediated gene knockdown. RESULTS: Expression of ARL15,
      ARF1 and ARF6 was confirmed in RASF and OASF samples but ARL15 expression
      remained unaltered on TNF induction. Notably, ARL15 knockdown resulted in
      downregulation of IL6 and GAPDH, upregulation of adiponectin and adiponectin
      receptor I genes; and significant reduction in migration and invasion of RASF.
      Genemania showed significant interactions of ARL15 with genes responsible for
      insulin resistance and phospholipase D. CONCLUSIONS: This first report on ARL15
      expression in RASF and its likely role in inflammation and metabolic syndromes
      through a TNF independent pathway, encourages hypothesis-free studies to identify
      additional pathways underlying RA disease biology.

PMID- 29465356
TI  - Does "time heal all wounds" still have a future in osteoarthritis?

PMID- 29465357
TI  - Molecular recognition patterns of anti-topoisomerase I-antibodies in patients
      with systemic sclerosis before and after autologous stem cell transplantation.
AB  - OBJECTIVES: To evaluate the effect of autologous stem cell transplantation (aSCT)
      on antibody (ab) reactivity towards linear epitopes of topoisomerase-I (topo
      I/Scl70) in patients with systemic sclerosis (SSc) and to correlate antibody
      reactivities with clinical outcome after aSCT. METHODS: Fourteen anti-topo
      I/Scl70-positive SSc-patients were analysed before and after non-myeloablative
      aSCT. Five patients showed ongoing good response (group 1), 9 had primarily
      responded but later relapsed or did not respond (group 2). Patients' sera were
      tested by ELISA against full length (fl) topo-I and 45 overlapping 25-mer
      peptides. Furthermore, for comparison sera from patients with anti-topo-I
      negative SSc (n=12), other collagen disorders (n=6), and from 21 healthy controls
      (HC) were analysed. RESULTS: Anti-topo-I-positive SSc-sera showed significantly
      higher IgG-reactivity as compared to HC towards 34 of the 45 peptides. Especially
      peptide 39 (aa647-671) emerged as a immunodominant epitope being recognised
      predominantly by anti-topo-I-positive SSc-sera. Reactivity towards 17 of the 45
      peptides decreased after aSCT in group 1- and 2-patients. Before aSCT, group 1
      patients had lower antibody reactivity towards peptide 39 than group 2-patients.
      There was no change in peptide-specificity after aSCT. CONCLUSIONS: Reactivity
      towards topo-I-epitopes is heterogeneous in SSc, but peptide 39 (aa647-671) may
      be another immunodominant epitope besides the published epitope aa489-573.
      Antibody reactivity to this peptide 39 was higher in group 2- than in group 1
      patients. Peptide recognition pattern did not change after aSCT.

PMID- 29465358
TI  - Bickerstaff brainstem encephalitis in a patient with ankylosing spondylitis on
      tumour necrosis factor-alpha inhibitor.

PMID- 29465359
TI  - Socio-economic inequalities in occurrence and health care costs in rheumatic and
      musculoskeletal diseases: results from a Spanish population-based study including
      1.9 million persons.
AB  - OBJECTIVES: To explore and compare the impact of socio-economic deprivation on
      the occurrence of the major rheumatic and musculoskeletal diseases (RMDs) and
      health care costs. METHODS: Data on diagnoses, socio-demographics and health care
      costs of the entire adult population of the Basque Country (Spain) was used. Area
      deprivation index included five categories (1 to 5 (most deprived)). Cost
      categories included primary and specialist care, emergency room,
      hospitalisations, and drug prescriptions. Twenty-nine RMDs were grouped into
      seven groups: Rheumatoid Arthritis, Spondyloarthritis, Crystal Arthropathies,
      Osteoarthritis, Soft Tissue Diseases, Connective Tissue Diseases, and Vasculitis.
      The relations between the deprivation and the occurrence of RMD and costs were
      explored in regression models adjusted for relevant confounders. RESULTS: Data
      from 1,923,156 adults were analysed. Mean age was 49.9 (SD18.4) years, 49% were
      males. Soft tissue diseases were the most prevalent RMD (5.5%, n=105,656),
      followed by osteoarthritis (2.2%, n=41,924). Socio-economic deprivation was
      associated with higher likelihood to have any of the 29 RMDs. The strongest socio
      economic gradient was seen for the soft tissue diseases (OR 1.82 [95%CI
      1.78;1.85], most vs. least deprived), followed by osteoarthritis (OR 1.59
      [1.54;1.64]). Deprivation was also associated with higher costs across the
      majority of the conditions however patterns were more blurred, and inverse
      relationship was observed for connective tissue diseases, gout, hip
      osteoarthritis and undifferentiated (poly)arthritis. CONCLUSIONS: Socio-economic
      deprivation is associated with increased occurrence of all RMDs, and in most
      cases more deprived patients incur higher health care costs.

PMID- 29465360
TI  - Serum soluble interleukin-2 receptor is a useful biomarker for disease activity
      but not for differential diagnosis in IgG4-related disease and primary Sjogren's
      syndrome adults from a defined population.
AB  - OBJECTIVES: To identify biomarkers for disease activity in IgG4-related disease
      (IgG4-RD) and primary Sjogren's syndrome (pSS). METHODS: Forty-three consecutive
      treatment-naive patients with IgG4-RD, 62 patients with pSS, and 5 patients with
      sicca syndrome were enrolled. IgG4-RD and pSS disease activity was assessed based
      on the IgG4-RD responder index (IgG4-RD RI) and EULAR Sjogren's Syndrome Disease
      Activity Index (ES- SDAI), respectively. The associations of biomarkers with
      disease activity were examined. RESULTS: Comparison of the three dis- eases
      identified the serum levels of IgG, IgG4, IgG4/IgG ratio, IgE, and soluble
      interleukin-2 receptor (sIL-2R) for IgG4-RD and the serum levels of IgM and sIL
      2R and lymphocyte counts for pSS as potential biomarkers of disease activity.
      Among these, serum sIL-2R levels correlate with baseline IgG4-RD RI scores and
      the number of affected organs in IgG4-RD (rho=0.74, p<0.0001 and rho=0.75,
      p<0.0001, respectively). Serum sIL-2R levels also correlate with ESSDAI scores
      and the number of af- fected organs in pSS (rho=0.67, p<0.0001 and rho=0.41,
      p<0.0001, respectively). Receiver operating characteristic curve analysis
      suggested serum sIL-2R levels as an efficient biomarker to distinguish the
      presence of extra-dacryosialadenitis involvements in IgG4-RD with a cut-off value
      of 424 U/mL (AUC=0.93, p<0.0001), and in pSS with 452 U/mL (AUC=0.89, p<0.0001).
      Serum sIL-2R levels decreased significantly after treatment in patients with IgG4
      RD and pSS. CONCLUSIONS: Serum sIL-2R levels are a potentially valuable biomarker
      for evaluating disease activity and treatment response in IgG4-RD and pSS.

PMID- 29465362
TI  - Development of systemic sclerosis in transgender females: a case series and
      review of the literature.
AB  - OBJECTIVES: Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue
      disease with a female predominance. The reason for the female predilection in SSc
      may relate to the difference in hormones between the genders. There are no
      current data on the influence male-to-female sex transition may have in the
      development of SSc. We report three patients who developed SSc after initiating
      the transgender process, and review current literature in regards to transgender
      patients with connective tissue disease (CTD). METHODS: We describe the clinical
      features and disease course of three transgender patients who developed SSc after
      their transition from male-to-female, who presented to our centre. Two additional
      transgender cases de- scribed in the literature with CTD were included in this
      review. RESULTS: All three patients developed SSc after having started the
      hormonal therapy required to transition. Two patients had surgical procedures
      preceding their diagnosis of SSc. Antibody profile, time of onset and disease
      features differed among our patients. Hormonal therapies were continued in all
      patients and they received the standard therapy for SSc. One patient died from
      complications of her disease. Only two cases describing the development of CTD in
      transgender patients were identified in the literature and both of these patients
      were diagnosed with systemic lupus erythematosus (SLE). CONCLUSIONS: This case
      series suggests that the hormonal modification as part of gender transition may
      be relevant in development of SSc. No further conclusions can be drawn on the
      continuation or not of HT.

PMID- 29465361
TI  - Superior oblique myositis causing acquired Brown's syndrome as the first
      manifestation of primary Sjogren's syndrome.

PMID- 29465363
TI  - Inhibitory effect and mechanism of 1,25-dihydroxy vitamin D3 on RANKL expression
      in fibroblast-like synoviocytes and osteoclast-like cell formation induced by IL
      22 in rheumatoid arthritis.
AB  - OBJECTIVES: To explore the inhibitory effect and mechanism of 1,25-dihydroxy
      vitamin D3 (l,25(OH)2D3) on receptor activator of nuclear factor-kappaB ligand
      (RANKL) expression in fibroblast-like synoviocytes (FLSs) and osteoclastogenesis
      induced by interleukin (IL)-22 in patients with rheumatoid arthritis (RA).
      METHODS: Fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA
      FLSs) were cultured and stimulated for RANKL expression with IL-22 in the absence
      or presence of various concentrations of l,25(OH)2D3, and JAK-2 inhibitor or p38
      MAPK inhibitor at the optimised time point of IL-22 treatment. The level of RANKL
      messenger RNA (mRNA) or protein was measured using real-time polymerase chain
      reaction (RT-PCR) or western blot method. To assess the impact of l,25(OH)2D3 on
      osteoclastogenesis, isolated monocytes were activated by M-CSF and RANKL or
      cocultured with FLSs stimulated by IL-22 in the presence or absence of
      l,25(OH)2D3 and those inhibitors. TRAP-positive cells as differentiated
      osteoclasts were stained for alkaline phosphatase. RESULTS: FLSs stimulated with
      IL-22 for 72 hours were used in further experiment because of the highest
      expression of RANKL at this time point. The expression of RANKL mRNA and protein
      in IL-22-stimulated FLSs were significantly inhibited by 1 nM of 1,25(OH)2D3
      (p<0.05). Interestingly, this inhibition was reversed by inhibitor of JAK-2/STAT
      3 or p38 MAPK/NF-kappaB signalling. In monocytes cocultured with IL-22-stimulated
      FLSs in the presence of exogenous RANKL and M-CSF, 1,25(OH)2D3 could block the
      process of osteoclastogenesis by JAK-2/STAT-3 or p38 MAPK/NF-kappaB signalling.
      CONCLUSIONS: 1,25(OH)2D3 may exert inhibitory effect on osteoclastogenesis of RA
      FLSs by down-regulating RANKL expression, which could be mediated by IL-22
      through JAK-2/STAT-3 and p38 MAPK/NF-kappaB signalling.

PMID- 29465364
TI  - Autologous fat transfer in the successful treatment of upper limb linear
      morphoea.

PMID- 29465365
TI  - Polyarteritis nodosa revisited: a review of historical approaches, subphenotypes
      and a research agenda.
AB  - Polyarteritis nodosa (PAN) is a rare form of primary systemic vasculitis with
      heterogeneous presentations, treatments and disease course. Historical approaches
      to classification and diagnostic terminology are reviewed. Since differentiation
      of PAN from microscopic polyangiitis (MPA) and other ANCA vasculitides by the
      Chapel Hill conference statements, and with hepatitis associated PAN defined as a
      secondary vasculitis, the phenotyping and subclassification of PAN has received
      little attention. Monogenic disorders similar to PAN have been described
      (familial Mediterranean fever, Adenosine Deaminase-2 deficiency), and cutaneous
      PAN and single organ vasculitis, discussed. The overlapping phenotypes between
      PAN and other primary vasculitic syndromes and subphenotypes within PAN are
      explored. This work will underpin development of newer treatment regimens and
      future genetic and related aetiologic studies.

PMID- 29465366
TI  - Cancer development in Korean patients with ANCA-associated vasculitis: a single
      centre study.
AB  - OBJECTIVES: We investigated the incidence rate and type of cancer, and
      furthermore, estimated the standardised incidence ratios (SIRs) of cancer in
      patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis
      (AAV) in Korea. METHODS: We retrospectively included 150 patients with AAV [81
      patients with microscopic polyangiitis (MPA), 38 with granulomatosis with
      polyangiitis (GPA) and 31 patients with eosinophilic GPA (EGPA)], and reviewed
      their medical records. We collected demographic, clinical and laboratory data,
      and reviewed the use of glucocorticoid and immunosuppressive drugs administered
      until detection of cancer or last visit. We estimated the SIRs of cancer
      according to totality, gender, age, AAV variants and each type of cancer.
      RESULTS: The mean age at diagnosis of AAV was 55.2 years and that at last visit
      was 59.5 years. The mean follow-up duration was 50.7 months. Four of 150 AAV
      patients had cancer (2.7%), and they got four different types of cancers
      including gastric cancer, lung cancer, prostate cancer and Non-Hodgkin lymphoma.
      Two patients exhibited gap-time from AAV to malignancy less than one year, and
      the rest of them exhibited gap-time of 8 and 6 years, respectively. The overall
      SIR of cancer in AAV patients was 1.43 (95% confidence interval 0.391, 3.671).
      The SIRs of cancer based on gender, and age at cancer or last visit, AAV variants
      and each type of cancer were not significant, either. CONCLUSIONS: The risk of
      cancer is low in Korean patients with AAV.

PMID- 29465367
TI  - Proprotein convertase enzyme FURIN is upregulated in primary Sjogren's syndrome.
AB  - OBJECTIVES: The proprotein convertase enzyme FURIN is a critical regulator of the
      anti-inflammatory TGFbeta-1 cytokine and peripheral immune tolerance. In T cells,
      FURIN is co-regulated with IFN-gamma and thus highly expressed in T helper 1 type
      cells. Previous studies have demonstrated that FURIN is upregulated in
      inflammatory conditions, including atherosclerosis, rheumatoid arthritis and
      systemic lupus erythematosus. Here, we evaluated the levels of FURIN in the
      plasma and peripheral blood mononuclear cells (PBMCs) of patients with primary
      Sjogren's syndrome (pSS) and in healthy controls. METHODS: FURIN plasma levels
      were determined by ELISA, and the mRNA expression in PBMCs was quantitated using
      qPCR. FURIN levels in the plasma were correlated with the clinical and
      demographic characteristics of the patients. RESULTS: FURIN was found to be
      significantly upregulated at both the protein and mRNA level in pSS patients
      compared to healthy controls. In pSS patients, high FURIN protein levels were
      significantly associated with elevated IFN-gamma levels in the plasma as well as
      a longer duration of sicca symptoms in the eyes. pSS patients with high FURIN
      levels in their plasma showed a trend towards lower levels of serum beta-2
      microglobulin, ESR and a lower systemic disease activity index ESSDAI.
      CONCLUSIONS: The proprotein convertase FURIN is significantly upregulated in pSS.
      Elevated FURIN levels associate with high levels of the Th1 type cytokine IFN
      gamma and long duration of dry eye symptoms. Patients with high FURIN levels show
      signs of lower disease activity suggesting that FURIN might have a protective
      role in pSS.

PMID- 29465368
TI  - Comparative effectiveness of glucosamine, chondroitin, acetaminophen or celecoxib
      for the treatment of knee and/or hip osteoarthritis: a network meta-analysis.
AB  - OBJECTIVES: To compare the efficacies of oral glucosamine, chondroitin, the
      combination of glucosamine and chondroitin, acetaminophen and celecoxib on the
      treatment of knee and/or hip osteoarthritis. METHODS: We searched electronic
      databases including PubMed, Embase, and Cochrane Library and the reference lists
      of relevant articles published from inception to October 23, 2017. A Bayesian
      hierarchical random effects model was used to examine the overall effect size
      among mixed multiple interventions. RESULTS: We identified 61 randomised
      controlled trials of patients with knee and/or hip osteoarthritis. There was no
      obvious difference in the results between the traditional meta-analysis and the
      network meta-analysis. The network meta-analysis demonstrated that celecoxib was
      most likely the best option (SMD, -0.32 [95% CI, -0.38 to -0.25]) for pain,
      followed by the combination of glucosamine and chondroitin. For physical
      function, all interventions were significantly superior to oral placebo except
      for acetaminophen. In terms of stiffness, glucosamine (SMD, -0.36 [95% CI, -0.67
      to -0.06]) and celecoxib (SMD, -0.29 [95% CI, -0.51 to -0.08]) were significantly
      better compared to placebo. In view of safety, compared to placebo only,
      celecoxib and acetaminophen presented significant differences. CONCLUSIONS: Given
      the effectiveness of these non-steroidal anti-inflammatory drugs and symptomatic
      slow-acting drugs, oral celecoxib is more effective than placebo on relieving
      pain and improving physical function, followed by the combination of glucosamine
      and chondroitin. Acetaminophen is likely the least efficacious intervention
      option. This information, accompanied by the tolerability and economic costs of
      the included treatments, would be conducive to making decisions for clinicians.

PMID- 29465369
TI  - Altered gene expression profiles of histone lysine methyltransferases and
      demethylases in rheumatoid arthritis synovial fibroblasts.
AB  - OBJECTIVES: Aberrant histone lysine methylation (HKM) has been reported in
      rheumatoid arthritis (RA) synovial fibroblasts (SFs). As histone lysine
      methyltransferases (HKMTs) and demethylases (HKDMs) regulate HKM, these enzymes
      are believed to be dysregulated in RASFs. The aim of this study is to clarify
      whether gene expressions of HKMTs and HKDMs are altered in RASFs. METHODS: SFs
      were isolated from synovial tissues obtained from RA or osteoarthritis (OA)
      patients during total knee joint replacement. The mRNA levels of 34 HKMTs and 22
      HKDMs were examined after stimulation with tumour necrosis factor alpha (TNF
      alpha) in RASFs and OASFs. RESULTS: The gene expression of the 12 HKMTs,
      including MLL1, MLL3, SUV39H1, SUV39H2, PRDM2, EZH2, SETD2, NSD2, NSD3, SMYD4,
      DOT1, and PR-set7, that catalyse the methylation of H3K4, H3K9, H3K27, H3K36,
      H3K79, or H4K20 was higher after TNFalpha stimulation in RASFs vs. OASFs. The
      gene expression of the 4 HKDMs, including FBXL10, NO66, JMJD2D, and FBXL11, that
      catalyse the methylation of H3K4, H3K9, or H3K36 was higher after TNFalpha
      stimulation in RASFs vs. OASFs. CONCLUSIONS: The study findings suggest that the
      HKM-modifying enzymes are involved in the alteration of HKM, which results in
      changes in the gene expression of RASFs.

PMID- 29465370
TI  - The initial predictors of death in 153 patients with ANCA-associated vasculitis
      in a single Korean centre.
AB  - OBJECTIVES: We estimated the cumulative patient survival rates, the causes of
      death and the initial predictors of death in Korean patients with microscopic
      polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA
      (EGPA). METHODS: We reviewed the medical records of 153 patients with
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We
      collected clinical and laboratory data including ANCA, Birmingham vasculitis
      activity score (BVAS), five factor score (FFS) (2009), comorbidities, medications
      and prognosis (death and relapse). The hazard ratio (HR) of variables at
      diagnosis for death in the disease course was assessed by the Cox hazard model
      analysis. RESULTS: The mean age of 153 AAV patients (47 men and 106 women) was
      55.2 years and the mean follow-up duration was 51.5 months. Fourteen of 153
      patients (9.2%) died (7 MPA and 7 GPA patients) during the mean follow-up of 56.9
      months. In all patients with AAV, 1 year-, 5 year- and 10 year-cumulative patient
      survival rates were 96.1%, 94.8% and 92.8%, respectively. The most common cause
      of death was infection of various causes. FFS (2009) >=2 (HR 16.520, p=0.012) and
      diffuse alveolar haemorrhage (DAH) (HR 3.705, p=0.042) at diagnosis could predict
      death during the follow-up in AAV patients in multivariate COX regression
      analysis. CONCLUSIONS: The overall mortality rate was 9.2% and 10-year cumulative
      patient survival rate was 92.8%. At diagnosis, FFS (2009) >= 2 and DAH were
      independent predictors of death during the follow-up in Korean patients with MPA,
      GPA and EGPA.

PMID- 29465372
TI  - Tocilizumab for the treatment of patients with rheumatoid arthritis and
      interstitial lung diseases: a case series.

PMID- 29465371
TI  - Long-term effects of the new direct antiviral agents (DAAs) therapy for HCV
      related mixed cryoglobulinaemia without renal involvement: a multicentre open
      label study.
AB  - OBJECTIVES: To investigate the long-term effects and safety of new direct anti
      viral agents (DAAs) in patients with hepatitis C virus (HCV)-related mixed
      cryoglobulinaemia (MC) without renal involvement. METHODS: The study enrolled 22
      consecutive patients, 19 received sofosbuvir-based regimen and three patients
      received other DAAs, individually tailored according to latest guidelines. As of
      December 2016, the median length of follow-up was 17 months (range 13-21).
      RESULTS: Extra-hepatic manifestations at enrollment were: purpura and arthralgia
      (12 cases), peripheral neuropathy (10 cases) and marginal zone B- lymphomas (2
      cases). After a four-week DAA therapy, all patients became HCV- negative.
      Moreover, after 48 weeks since the beginning of DAA treatment, sustained
      regression of purpura and arthralgias was observed respectively in eight and in
      nine cases; peripheral neuropathy improved in seven cases, and cryocrit median
      values decreased from three (1-20) at baseline to two (1-12) after 48 weeks. Two
      cases with indolent marginal zone lymphomas did not show any haematological
      response: size and number of the involved nodes remained unchanged. In addition,
      the monoclonal B-cell population found in the peripheral blood in four cases did
      not disappear after recovery from HCV- RNA. Mild side effects occurred in nine
      patients, but six patients developed ribavirin-related anaemia requiring
      reduction of ribavirin dose. CONCLUSIONS: DAA therapy is safe and effective to
      eradicate HCV in MC, but seems associated with satisfactory clinical response in
      mild or moderate cryoglobulinaemic vasculitis and no response in B-NHL.

PMID- 29465373
TI  - Anti-alpha-enolase antibodies in Behcet's disease: a marker of mucocutaneous and
      articular disease activity?
AB  - OBJECTIVES: To assess IgM anti-alpha-enolase antibodies (AAEA) in systemic
      Behcet's disease (BD) and its possible association with clinical manifestations
      and disease activity. METHODS: Ninety-seven consecutively selected BD patients
      were compared to 36 enteropathic spondyloarthritis (ESpA) [24 Crohn's disease
      (CD) and 12 ulcerative colitis (UC)] patients and 87 healthy controls. IgM AAEA
      was detected by immunoblotting. Disease activity was assessed by standardised
      indexes, Brazilian BD Current Activity Form (BR-BDCAF) for BD and Harvey-Bradshaw
      Index (HBI) for CD and UC patients. A second evaluation was performed in BD
      patients (n=56), regarding IgM AAEA presence, disease activity scores and C
      reactive protein (CRP). RESULTS: Higher IgM AAEA prevalence was found in 97 BD
      (17.7%) compared to ESpA (2.8%) and healthy controls (2.3%), p<0.001. IgM AAEA
      frequency was higher in active BD compared to inactive BD (30.2% vs. 7.4%,
      p=0.006), a finding confirmed in the second cross-sectional evaluation of 56 of
      these BD patients (45.5% vs. 13.3%, p=0.02). Mean BR-BDCAF scores were higher in
      IgM AAEA positive group on both evaluations (9.1 +/- 5.4 vs. 4.9 +/- 4.9,
      p=0.002; 5.0 +/- 4.9 vs. 2.2 +/- 2.9, p=0.01, respectively). BD patients with
      mucocutaneous and articular symptoms presented higher IgM AAEA positivity in the
      first and second evaluations (64.7% vs. 27.5%, p=0.005; 36.4% vs. 7.1%, p=0.039
      respectively). CONCLUSIONS: Our data support the notion that alpha-enolase is a
      target antigen in BD, particularly associated with disease activity,
      mucocutaneous and articular involvement. In addition, IgM AAEA may distinguish BD
      from ESpA, especially in patients with high disease activity.

PMID- 29465374
TI  - No specific imaging pattern can help differentiate IgG4-related disease from
      idiopathic retroperitoneal fibrosis: 18 histologically proven cases.
AB  - OBJECTIVES: Retroperitoneal fibrosis (RPF) is a rare disease, with unknown
      aetiology (idiopathic RPF: iRPF) in two-thirds of cases. A subset of iRPF may be
      a manifestation of IgG4-related disease (IgG4-RD). Thus, recognition of IgG4-RD
      RPF is crucial to optimise patient's care with iRPF. The current study aimed to
      examine imaging specific patterns, which could help differentiate between IgG4-RD
      RPF and iRPF, and thus skip performing biopsies. METHODS: This analysis included
      patients with iRPF and a retroperitoneal biopsy at the Lille University Hospital,
      France. We reviewed their baseline characteristics, clinical presentation,
      biological results and imaging features. Patients were classified in 3 groups
      according to histopathological characteristics of IgG4-RD as follows: highly
      suggestive of IgG4-RD, possible IgG4-RD, or non-evocative of IgG4-RD. RESULTS: Of
      the 18 patients analysed in the study, 4 (22%) patients had highly suggestive
      IgG4-RD-RPF, 8 (44%) possible IgG4-RD-RPF and 6 (33%) non-evocative IgG4-RD. We
      found no clinical, biological features nor specific imaging pattern that could
      help differentiate between the 3 groups. CONCLUSIONS: After ruling out all known
      causes of RPF, retroperitoneal biopsy is still necessary to ascertain the
      diagnosis of IgG4-RD-RPF. No specific pattern can be used to distinguish between
      IgG4-RD-RPF and iRFP.

PMID- 29465375
TI  - Pauci-immune crescentic glomerulonephritis in a patient with B-lymphocyte
      poly/autoreactivity.

PMID- 29465376
TI  - Efficient detection of pulmonary arterial hypertension using serum haptoglobin
      level and cardiac MRI in patients with connective tissue diseases: a pilot study.

PMID- 29465377
TI  - Determination of benzalkonium chloride in wet wipes by using a validated
      capillary electrophoresis method.
AB  - Benzalkonium chloride (BAC), which is a mixture of C8 and C18
      alkylbenzyldimethylammonium chlorides, has an important biocide character and is
      used in many cosmetics, especially wet wipes, as a preservative and/or
      antibacterial agent. The concentration range of BAC is 0.005-0.5 % and it is an
      irritant substance when used at high concentrations. Thus, the concentration of
      BAC should be carefully monitored in commercial products intended for skin use.
      In this study, a capillary electrophoresis (CE) analysis method for BAC
      quantification was developed. The quantitative analysis was carried out by the
      external standard method. The electrophoretic separation was performed by using
      75 mM (pH 6.0) phosphate buffer solution containing 30% acetonitrile as the
      electrolyte. The separation voltage was 10 kV and the temperature was held at 18
      degrees C. Samples were introduced into the capillary column hydrodynamically
      using 50.0-mbar pressure over a 3-s period. The developed method was validated
      and applied on samples prepared by wringing out antibacterial wet wipes
      containing BAC without any further extraction. The linearity of the method was
      controlled by applying the Mandel test. The limit of detection (LOD) values for
      the developed method were 0.313 and 0.309 ug/ml and the limit of quantification
      (LOQ) values were 1.042 and 1.029 ug/ml for C10 and C12 derivatives,
      respectively.

PMID- 29465378
TI  - Investigation of water-soluble elastin as a multifunctional cosmetic material:
      Moisturizing and whitening effects.
AB  - Elastin and collagen are extracellular matrix proteins that are widely
      distributed in the body. Although elastin essentially functions as a skin
      moisturizer, there have been few reports on its other fundamental chemical and
      biological functions. In this study, we investigated the moisturizing and
      whitening (tyrosinase inhibition) effects of elastin to examine its usefulness as
      a cosmetic material. Water-soluble hot alkali pig aorta (HAPA)-elastin was
      prepared from pig aorta using the hot alkali method. HAPA-elastin showed a widely
      distributed molecular weight and had a coacervation property that mediated
      reversible self-assembly of its molecules with increasing temperature. Amino acid
      analysis of HAPA-elastin showed a high content (81.5%) of hydrophobic amino acids
      such as Gly, Ala, Val, and Pro. Des (desmosine) and Ide (isodesmosine), which are
      characteristic amino acids of elastin, accounted for more than 0.4% of the total
      amino acid content. HAPA-elastin showed a moisture-retaining property. The water
      content of skin samples treated with and without HAPA-elastin was 77.2% +/- 7.8%
      and 49.4% +/- 10.1%, respectively. HAPA-elastin also inhibited tyrosinase
      activity by 11.3% +/- 3.9%. The results obtained indicate that elastin has a
      useful function as a cosmetic material.

PMID- 29465379
TI  - Effect of SIRT6 knockdown on NF-kappaB induction and on residual DNA damage in
      cultured human skin fibroblasts.
AB  - SIRT6 is a member of the sirtuin family, which is involved in multiple cellular
      pathways related to aging, inflammation, epigenetics, and a variety of other
      cellular functions, including DNA repair (1). Multiple pathways involving
      different cellular functions are impacted by the deacetylase activity of SIRT6.
      Genomic integrity is maintained by the capacity of SIRT6 to modulate the
      accessibility of DNA repair proteins. Glucose metabolism is suppressed by SIRT6
      via the deacetylation of histones located at the promoter regions of multiple
      glycolytic genes and the corepression of hypoxia-inducible factor-1alpha. SIRT6
      is also a corepressor of nuclear factor (NF)-kappaB, silencing NF-kappaB target
      genes through the deacetylation of histones at their promoters' regions. We used
      SIRT6 small-interfering RNA as a tool to modulate residual DNA damage and NF
      kappaB expression in human dermal fibroblasts. We measured NF-kappaB levels in
      the presence or the absence of ultraviolet B (UVB). The impact of SIRT6 knockdown
      as shown by a decrease in SIRT6 messenger RNA levels resulted in residual DNA
      damage as evaluated by the comet assay. Our results show that NF-kappaB was
      increased significantly (up to 400%) due to SIRT6 silencing in the absence of
      UVB, illustrating the master regulatory function of SIRT6 in inflammation. We
      also found a significant increase in DNA damage without UV exposure as a result
      of SIRT6 silencing, indicating the importance of SIRT6 in DNA repair pathways in
      cultured human dermal fibroblasts.

PMID- 29465380
TI  - Collagen XVIII: A key interfacial component of the skin architecture.

PMID- 29465381
TI  - Designing new functional cosmetic ingredients from polyglycerol, a versatile bio
      based platform for improved sustainability.
AB  - Polyglycerol (PG) is a well-known cosmetic ingredient and important precursor for
      the synthesis of a variety of cosmetic ingredients, such as surfactants,
      emulsifiers, and conditioning agents for hair and skin. When derived from
      renewable resources, PG can provide a more sustainable platform for the
      development of new ingredients with improved performance in cosmetic
      applications. This paper will discuss recent advances in the utilization of bio
      based PG ingredients as alternatives to traditional ethoxylate chemistries for
      mild nonionic surfactants, substantive humectants, and micellar thickeners.

PMID- 29465382
TI  - Addressing epidemic of para-phenylenediamine sensitization by going forward into
      the past.

PMID- 29465383
TI  - An in vivo confocal Raman spectroscopic investigation of salicylic acid
      penetration: Variation with formulation parameters.
AB  - Salicylic acid (SA) is widely used in leave-on antiacne formulations, typically
      at a 2% level. As a beta-hydroxy acid, it is a milder active ingredient than
      either alpha-hydroxy acids or benzoyl peroxide. SA is a keratolytic agent, a
      bacteriocide, and a comedolytic agent. For these reasons, improving the
      efficiency of SA delivery is of interest. The objective of this work is to
      measure in vivo SA penetration from topically applied 2% SA leave-on products and
      to understand the penetration in terms of formulation parameters. Penetration of
      SA was measured in three depth zones-0-3 MUm, 3-6 MUm, and 6-9 MUm below the
      surface-using in vivo confocal Raman spectroscopy. The delivery of SA from an
      emulsion, pH 4.0, and a hydrogel, pH 3.75, was compared and contrasted. A
      comparison of depth profiles reveals, e.g., significant differences in SA
      distribution between-treatment profiles at various time points after treatment,
      particularly 3C6 MUm below the surface. The hydrogel exhibited the higher
      normalized level of SA in the 3-6 MUm depth zone. Confocal in vivo Raman
      spectroscopy is proving to be a valuable tool in determination of details of
      penetration of products into the skin. The penetration of various 2% SA anti-acne
      product forms will be compared and contrasted in this presentation. Delivery of
      SA will be discussed in terms of formulation parameters such as phase, pH, and
      specific ingredients and molecular-level interactions.

PMID- 29465384
TI  - A botanically derived skin surface lipid mimetic based on the composition of
      healthy 22-year-old females.
AB  - INTRODUCTION: Skin surface lipids (SSLs) greatly affect the skin physiology and
      are thought to be involved in skin processes such as thermoregulation, bacterial
      colonization, and barrier function and maintenance. SSLs are primarily composed
      of fatty acids, triglycerides, cholesterol, steryl esters, wax esters, and
      squalene. The objective of this research was to evaluate and better understand
      the SSL composition and variation in an age- and sex-controlled population, and
      create an appropriate botanically derived mimetic. METHODS: SSL samples taken
      from the foreheads of 59 healthy, 22-year-old females were analyzed by gas
      chromatography mass spectrometry (GC-MS). Using botanically derived raw materials
      from Macadamia integrifolia, Simmondsia chinensis, and Olea europaea, a mimetic
      was engineered via a series of esterification reactions and lipid components
      quantitated with GC-MS. The glyceride and wax ester components were produced by
      the interesterification of M. integrifolia and S. chinensis under specified
      conditions. The steryl ester component was produced by the esterification of the
      fatty acids of M. integrifolia and phytosterols under similar conditions.
      RESULTS: The following major classes of lipids were found and quantified by
      percent composition: glycerides, free fatty acids, squalene, wax esters, steryl
      esters, and cholesterol. The variability between subjects for each component was
      minimal; however, the greatest variation was seen for free fatty acids and
      cholesterol. Correlations among the components were calculated and found to be
      statistically or directionally significant with few exceptions. The
      esterification reactions of jojoba, macadamia, and tall oils, along with a
      precise addition of squalene derived from O. europaea, produced a suitable SSL
      mimetic. When applied to delipidized skin, the mimetic helped restore barrier
      function, increased skin hydration, and increased skin elasticity and firmness in
      aged skin. DISCUSSION: The present research indicates that, overall, the SSL
      composition is quite consistent in a controlled population of 22-year-old
      females. Furthermore, there were strong correlations between the SSL components
      among subjects, with the exception of squalene and steryl esters. This was
      expected due to the fact that of the six major SSL components, steryl esters and
      squalene also showed higher variation over time for each individual. The
      variation in free fatty acids may be attributable to the potential differences in
      the microflora of the subjects. The variation in this study's results, as
      compared to previously published work, could indicate that the collection
      methods, geographic location, gender, and age specificity contribute to the
      distribution or collection of different lipid components on the skin surface.
      Since the excretion of sebum is known to decrease in females after 40 years of
      age, the proposed mimetic could be a beneficial supplement to human SSLs in aged
      skin, as well as in skin where the stratum corneum is defective, by aiding in the
      restoration of barrier function, while increasing skin hydration, elasticity, and
      firmness.

PMID- 29465385
TI  - Address the epidemic of p-phenylenediamine sensitization and aid marginal farmers
      in a changing climate.

PMID- 29465386
TI  - Silicone elastomer blends: A novel topical drug delivery platform.

PMID- 29465387
TI  - Typology and atlases of human fingernails across ages and ethnicities.

PMID- 29465388
TI  - New bioprinted skin, cosmetic in vitro model.
AB  - We developed a new evolution of three-dimensional skin equivalent due to the
      optimization of four-dimensional laser-assisted bioprinting and skin equivalent
      culture protocols. This allowed us to produce fully bioprinted skin equivalents
      that are closed to current skin equivalents and suitable to test cosmetic
      ingredients. Particularly, we performed preliminary evaluation of maturogens to
      improve the dermis maturation before the epidermal seeding and we designed a
      specific "micropattern" to reproduce the nonlinear aspect of the dermal-epidermal
      junction. Finally an active ingredient was applied during the production of the
      bioprinted skin equivalent.

PMID- 29465389
TI  - A general formulation strategy toward long-wear color cosmetics with sebum
      resistance.
AB  - We propose a "Soft" + "Hard" formulation strategy for long-wear and sebum/oil
      resistant makeup. The ratios of "Hard" nonvolatile components (e.g., resins,
      particulates, and solid emulsifiers) and compatible "Soft" nonvolatile components
      (e.g., nonvolatile oils and liquid emulsifiers) may be carefully adjusted to
      create desired long-wear performance and sensory. For a given formulation
      chassis, we recommend studying compatibility and viscoelastic profiles of blends
      made of "Hard" polymeric resins and "Soft" structuring polymers to gain
      fundamental understanding of the polymer matrix for pigment adhesion. Enhanced
      oil/sebum resistance may be achieved, where there is good compatibility among the
      "Soft" and "Hard" polymeric components and where there is considerable
      immiscibility between oil/sebum and each nonvolatile component. Our strategy may
      help promote cosmetic formulation development based on rational design and
      understanding interactions among components, develop novel long-wear formulation
      chassis, and properly evaluate emerging new technologies.

PMID- 29465390
TI  - New nature-inspired urocanic acid mimic preventing DNA damages and
      immunosuppressive signalling induced by ultraviolet-B radiations.

PMID- 29465391
TI  - New targets in the battle against dandruff.
AB  - Dandruff is a scalp disorder characterized by flaking skin and itch of an
      excessive oily scalp skin. It affects 55% of the global youth and adult
      population. Seborrheic dermatitis is a similar scalp skin disorder with
      aggravated itchy rashes and flaking. Different factors are identified in the
      dandruff development: increased sebum production, uncontrolled fungal growth of
      Malassezia strains and individual reaction to pro-inflammatory environment, and
      the susceptibility to trigger an immunological response. Using in vitro and ex
      vivo models, we show that an Epilobium angustifolium extract dose dependently
      reduces lipid synthesis in sebocytes to a maximum of -43% (1% extract), and
      protects the epidermis from Malassezia-induced morphological changes. Epilobium
      angustifolium extract also acts through innovative mechanisms involving
      regulations of defensins (human beta-defensins [hBD2] and hBD3) and toll-like
      receptor 2 involved in the immunological response of the skin. The anti-dandruff
      and sebum-regulating efficacy of E. angustifolium extract (1.5%) was confirmed in
      a clinical study that mobilized 24 volunteers with dandruff and greasy scalp for
      30 days. At the end of the study, nonadherent and adherent dandruffs were
      significantly (p < 0.0001) reduced in average by -54% and -48%, respectively.
      Using Sebumeter(r) measurements, scalp sebum production was inhibited by -67% (p
      < 0.0001) in average over baseline. In conclusion, E. angustifolium extract
      offers a new innovative approach to dandruff reduction through immunomodulation
      of the skin response to Malassezia invasion.

PMID- 29465392
TI  - Structure/property comparisons of chemistries based on renewable 1,3-propanediol
      and petroleum-derived alkylene oxides.
AB  - Structure/property comparisons were made of chemistries based on renewable 1,3
      propanediol (PDO)- versus petroleum-based alkylene oxides as well as comparisons
      of the respective polyethers, emulsifiers, and cosmetic formulations based on
      these feedstocks. Green Chemistry Principles were applied in the manufacture of
      polyethylene glycol (PEG)-free renewable PDO-based oligomers and PDO-based fatty
      acid ester emulsifiers. Sustainable cosmetic products formulated with renewable
      PDO-based emulsifiers gave equivalent performance in sensory and moisturization
      evaluations compared to those formulated with the petroleum-derived PEG-based
      emulsifiers.

PMID- 29465393
TI  - Unique natural exopolysaccharides for biomimetic protective effect against urban
      pollution.
AB  - : Through natural selection, living organisms have evolved well-adapted survival
      strategies over time. The shallow salt waters of Moorea lagoon are the site of
      accumulation of microbial mats called "Kopara," in the native Polynesian
      language. This unique ecosystem is rich in film-forming exopolysaccharides (EPSs)
      secreted by microorganisms within the biofilm, as a mean to protect themselves
      from environmental stress (strong ultraviolet [UV], pH, salinity ... ). Using
      blue biotechnology, a manufacturing process was developed to obtain an EPS with
      skin benefits. The active ingredient (EPS-229) protects against urban pollution,
      including free radicals, heavy metals, hydrocarbons, and PM2.5 (particulate
      matter with a size lower than 2.5 MUm). METHODS: The anti-lipid peroxidation
      action of EPS-229 was studied in an in vitro UVB-irradiated keratinocyte culture
      model, using lipophilic fluorescent probe. The chelating properties of EPS-229
      were evaluated in tubo in the presence of cadmium and lead. The protective effect
      of EPS-229 on pollution-exposed skin explants was investigated through
      quantification of released malondialdehyde (MDA) and histological observation of
      skin morphology using optical microscopy. Clinical evaluation of the protective
      and cleansing efficacy of a water solution containing EPS-229 (0.02% and 0.01%
      w/v, respectively) was performed, against placebo, on a panel of 18 volunteers.
      For these studies, the forearms of volunteers were treated with EPS-229 before
      (anti-adhesion affect) or after (cleansing effect) application of PM2.5 (iron
      particles of 1 MUm). The presence of skin-adherent particles was observed and
      quantified by image analysis, using specific digital masks. RESULTS: In vitro,
      EPS-229 significantly protected keratinocyte cell membranes from lipid
      peroxidation. A decrease of 28% was achieved when a concentration of 0.001% w/v
      EPS-229 was applied to the cell culture. In tubo, EPS-229 also presented strong
      chelating properties. Maximal adsorption was estimated at 154 mg/g (1.37 mmol/g)
      of EPS-299 for cadmium and at 250 mg/g (1.21 mmol/g) of EPS-229 for lead. In the
      skin explant model of pollution exposure, EPS-229 (0.03% w/v) reduced MDA
      production by 44%, preserved cell integrity, improved dermal-epidermal cohesion,
      and normalized the collagen network. In vivo, treatment of skin with EPS-229
      before exposure to PM2.5 created a protective film limiting particle adhesion.
      When used in a cleansing solution after exposure to PM2.5, EPS-229 formed a mesh
      that entrapped particles and removed them from the skin surface. CONCLUSION:
      Inspired by the French Polynesia Kopara unique ecosystem, a bioactive
      exopolysaccharide (EPS-229) has been developed that offers protection from
      environmental aggression. As a biomimetic shield at the surface of the skin, EPS
      229 provides an immediate multiprotective action that efficiently fights the
      harmful effects of urban pollution and smog.

PMID- 29465394
TI  - Review of innovations to improve fragrance bloom, release, and retention on skin
      from surfactant-rich cosmetics.

PMID- 29465395
TI  - A unifying theory for visualizing the causes of hair breakage and subsequent
      strategies for mitigation.

PMID- 29465396
TI  - A dynamic mechanism for allosteric activation of Aurora kinase A by activation
      loop phosphorylation.
AB  - Many eukaryotic protein kinases are activated by phosphorylation on a specific
      conserved residue in the regulatory activation loop, a post-translational
      modification thought to stabilize the active DFG-In state of the catalytic
      domain. Here we use a battery of spectroscopic methods that track different
      catalytic elements of the kinase domain to show that the ~100 fold activation of
      the mitotic kinase Aurora A (AurA) by phosphorylation occurs without a population
      shift from the DFG-Out to the DFG-In state, and that the activation loop of the
      activated kinase remains highly dynamic. Instead, molecular dynamics simulations
      and electron paramagnetic resonance experiments show that phosphorylation
      triggers a switch within the DFG-In subpopulation from an autoinhibited DFG-In
      substate to an active DFG-In substate, leading to catalytic activation. This
      mechanism raises new questions about the functional role of the DFG-Out state in
      protein kinases.

PMID- 29465398
TI  - On the move.
AB  - The mechanisms by which a retrotransposon called LINE-1 duplicates itself and
      spreads through the human genome are becoming clearer.

PMID- 29465397
TI  - Molecular coordination of Staphylococcus aureus cell division.
AB  - The bacterial cell wall is essential for viability, but despite its ability to
      withstand internal turgor must remain dynamic to permit growth and division.
      Peptidoglycan is the major cell wall structural polymer, whose synthesis requires
      multiple interacting components. The human pathogen Staphylococcus aureus is a
      prolate spheroid that divides in three orthogonal planes. Here, we have
      integrated cellular morphology during division with molecular level resolution
      imaging of peptidoglycan synthesis and the components responsible. Synthesis
      occurs across the developing septal surface in a diffuse pattern, a necessity of
      the observed septal geometry, that is matched by variegated division component
      distribution. Synthesis continues after septal annulus completion, where the core
      division component FtsZ remains. The novel molecular level information requires
      re-evaluation of the growth and division processes leading to a new conceptual
      model, whereby the cell cycle is expedited by a set of functionally connected but
      not regularly distributed components.

PMID- 29465399
TI  - Learning place cells, grid cells and invariances with excitatory and inhibitory
      plasticity.
AB  - Neurons in the hippocampus and adjacent brain areas show a large diversity in
      their tuning to location and head direction, and the underlying circuit
      mechanisms are not yet resolved. In particular, it is unclear why certain cell
      types are selective to one spatial variable, but invariant to another. For
      example, place cells are typically invariant to head direction. We propose that
      all observed spatial tuning patterns - in both their selectivity and their
      invariance - arise from the same mechanism: Excitatory and inhibitory synaptic
      plasticity driven by the spatial tuning statistics of synaptic inputs. Using
      simulations and a mathematical analysis, we show that combined excitatory and
      inhibitory plasticity can lead to localized, grid-like or invariant activity.
      Combinations of different input statistics along different spatial dimensions
      reproduce all major spatial tuning patterns observed in rodents. Our proposed
      model is robust to changes in parameters, develops patterns on behavioral
      timescales and makes distinctive experimental predictions.

PMID- 29465402
TI  - Evidence-based medicine, transparency and reproducibility in research, and
      challenges for peer review.

PMID- 29465401
TI  - Adherence to Anaphylaxis Guidelines: Real-World Data From the Emergency
      Department of a Tertiary Hospital.
AB  - BACKGROUND AND OBJECTIVE: Few studies have evaluated adherence to anaphylaxis
      guidelines in emergency departments (EDs). Objective: The objective of this study
      was to evaluate adherence to anaphylaxis guidelines in the ED of a tertiary
      hospital. METHODS: Medical records of patients attended in the ED of University
      Hospital of Salamanca, Spain were reviewed. Those patients fulfilling the
      anaphylaxis criteria proposed by the NIAID/FAAN were selected. RESULTS: During a
      1-year period, we identified 89 patients (74 adults and 15 children). The
      anaphylactic reaction was moderate in 65% of adults, severe in 34%, and very
      severe in 1%. In children, all reactions were moderate. Fewer than half of the
      patients (42%) received adrenaline in the ED; this was administered
      intramuscularly in only 19% of cases. As for the severity of the reaction, 65% of
      patients with moderate reactions and 42% with severe reactions were not treated
      with adrenaline. At discharge from the ED, an adrenaline auto-injector was
      recommended to only 5.6% of patients. Fifty-two percent of patients received a
      documented allergy referral (57% adults vs 27% children, P=.047), 29%
      instructions about avoidance of triggers (31% adults vs 20% children, NS), and
      51% written instructions for recognition of anaphylaxis warning signs (41% adults
      vs 100% children, P<.001). CONCLUSIONS: The results of the study show a large
      discrepancy between recommendations in guidelines and management of anaphylaxis
      in the ED. Additional training efforts are needed to improve the treatment of
      patients with anaphylactic reactions.

PMID- 29465400
TI  - Tumor initiating cells induce Cxcr4-mediated infiltration of pro-tumoral
      macrophages into the brain.
AB  - It is now clear that microglia and macrophages are present in brain tumors, but
      whether or how they affect initiation and development of tumors is not known.
      Exploiting the advantages of the zebrafish (Danio rerio) model, we showed that
      macrophages and microglia respond immediately upon oncogene activation in the
      brain. Overexpression of human AKT1 within neural cells of larval zebrafish led
      to a significant increase in the macrophage and microglia populations. By using a
      combination of transgenic and mutant zebrafish lines, we showed that this
      increase was caused by the infiltration of peripheral macrophages into the brain
      mediated via Sdf1b-Cxcr4b signaling. Intriguingly, confocal live imaging reveals
      highly dynamic interactions between macrophages/microglia and pre-neoplastic
      cells, which do not result in phagocytosis of pre-neoplastic cells. Finally,
      depletion of macrophages and microglia resulted in a significant reduction of
      oncogenic cell proliferation. Thus, macrophages and microglia show tumor
      promoting functions already during the earliest stages of the developing tumor
      microenvironment.

PMID- 29465403
TI  - Family or democracy - the cover page of our journal - a (resolved) dilemma for
      our editorial board.

PMID- 29465404
TI  - Concomitant mitral regurgitation: an insidious cause of lowflow, low-gradient
      severe aortic stenosis.

PMID- 29465405
TI  - The importance of large animal atherosclerosis models in studying the response to
      polymers and drug-eluting stents.

PMID- 29465407
TI  - Transcatheter tricuspid intervention: the new challenge of structural valve
      intervention.

PMID- 29465406
TI  - Micro-mesh technology in routine CAS: the final piece of the puzzle?

PMID- 29465408
TI  - How should I treat a bioresorbable vascular scaffold edge restenosis and intra
      scaffold dissection?

PMID- 29465409
TI  - Pressure and compressibility factor of bidisperse magnetic fluids.
AB  - In this work, we investigate the pressure and compressibility factors of
      bidisperse magnetic fluids with relatively weak dipolar interactions and
      different granulometric compositions. In order to study these properties, we
      employ the method of diagram expansion, taking into account two possible
      scenarios: (1) dipolar particles repel each other as hard spheres; (2) the
      polymer shell on the surface of the particles is modelled through a soft-sphere
      approximation. The theoretical predictions of the pressure and compressibility
      factors of bidisperse ferrofluids at different granulometric compositions are
      supported by data obtained by means of molecular dynamics computer simulations,
      which we also carried out for these systems. Both theory and simulations reveal
      that the pressure and compressibility factors decrease with growing dipolar
      correlations in the system, namely with an increasing fraction of large
      particles. We also demonstrate that even if dipolar interactions are too weak for
      any self-assembly to take place, the interparticle correlations lead to a
      qualitative change in the behaviour of the compressibility factors when compared
      to that of non-dipolar spheres, making the dependence monotonic.

PMID- 29465410
TI  - Mechanistics of biomass discharge during whole-heart decellularization.
AB  - Whole-organ engineering-based on the functional repopulation of acellular whole
      organ scaffolds derived from perfusion-based in toto decellularization of the
      specific organ system-is one of the most promising fields in tissue engineering.
      However, to date, we still have hardly any insights into the process of perfusion
      based scaffold generation itself, with human-scale scaffolds usually obtained by
      adoption of small animal decellularization models, although those organs are of
      decreased biomass and potentially different biological characteristics.
      Therefore, in this study we analyzed perfusion-based human-scale whole-heart
      decellularization by evaluating and comparing the dynamics of biomass discharge
      and its kinetic characteristics during in toto decellularization of ovine and
      rodent hearts, while introducing a theoretical model of biomass depletion during
      perfusion-based whole-heart decellularization. Our results suggest highly varying
      process characteristics for the in toto decellularization of individual human
      scale organs, such as protein discharge kinetics or time-dependent
      viscoelasticity of formed debris, despite seemingly consistent inter-sample
      decellularization efficacy, as evaluated by conventional disruptive analysis of
      obtained ECM scaffolds. Hence, the here exposed insights into the mechanistics of
      whole-heart decellularization as well as the introduced non-disruptive process
      accompanying tools may help to monitor and further optimize the decellularization
      process, especially with regards to human-scale scaffold production.

PMID- 29465411
TI  - Three-dimensional cotton-like nickel nanowire@Ni-Co hydroxide nanosheet arrays as
      binder-free electrode for high-performance asymmetric supercapacitor.
AB  - Three-dimensional (3D) cotton-like Ni-Co layered double hydroxide nanosheet
      arrays/nickel nanowires (3D Ni-Co LDH/NiNw) were successfully fabricated through
      a facile chemical bath deposition method. The 3D nickel nanowires are used as a
      conductive substrate with robust adhesion for high-pseudocapacitance Ni-Co LDH.
      The 3D Ni-Co LDH/NiNw electrode shows a high areal specific capacitance of 14 F
      cm-2 at 5 mA cm-2 and quality specific capacitance of 466.6 F g-1 at 0.125 A g-1
      with respect to the whole quality of the electrode. The fabricated asymmetric
      supercapacitor exhibits a remarkable energy density of 0.387 mWh cm-2 using Ni-Co
      LDH/NiNw as the negative electrode. This high-performance composite electrode
      presents a new and affordable general approach for supercapacitors.

PMID- 29465412
TI  - Magnetic particle imaging for in vivo blood flow velocity measurements in mice.
AB  - Magnetic particle imaging (MPI) is a new imaging technology. It is a potential
      candidate to be used for angiographic purposes, to study perfusion and cell
      migration. The aim of this work was to measure velocities of the flowing blood in
      the inferior vena cava of mice, using MPI, and to evaluate it in comparison with
      magnetic resonance imaging (MRI). A phantom mimicking the flow within the
      inferior vena cava with velocities of up to 21 cm s-1 was used for the evaluation
      of the applied analysis techniques. Time-density and distance-density analyses
      for bolus tracking were performed to calculate flow velocities. These findings
      were compared with the calibrated velocities set by a flow pump, and it can be
      concluded that velocities of up to 21 cm s-1 can be measured by MPI. A time
      density analysis using an arrival time estimation algorithm showed the best
      agreement with the preset velocities. In vivo measurements were performed in
      healthy FVB mice (n  =  10). MRI experiments were performed using phase contrast
      (PC) for velocity mapping. For MPI measurements, a standardized injection of a
      superparamagnetic iron oxide tracer was applied. In vivo MPI data were evaluated
      by a time-density analysis and compared to PC MRI. A Bland-Altman analysis
      revealed good agreement between the in vivo velocities acquired by MRI of 4.0  +/
      1.5 cm s-1 and those measured by MPI of 4.8  +/-  1.1 cm s-1. Magnetic particle
      imaging is a new tool with which to measure and quantify flow velocities. It is
      fast, radiation-free, and produces 3D images. It therefore offers the potential
      for vascular imaging.

PMID- 29465413
TI  - Facile synthesis of nickel-doped Co9S8 hollow nanoparticles with large surface
      controlled pseudocapacitive and fast sodium storage.
AB  - Transition metal sulfides are considered to be promising candidates as anodes for
      sodium ion batteries (SIBs). However, their further applications are limited by
      poor electrical conductivity and sluggish electrochemical kinetics. We report,
      for the first time, nickel-doped Co9S8 hollow nanoparticles as SIB anodes with
      enhanced electrical conductivity and a large pseudocapacitive effect, leading to
      fast kinetics. This compound exhibits excellent sodium storage performance,
      including a high capacity of 556.7 mA h g-1, a high rate capability of 2000 mA g
      1 and an excellent stability up to 200 cycles. The results demonstrate that
      nickel-doped Co9S8 hollow nanoparticles are a promising anode material for SIBs.

PMID- 29465414
TI  - Septal penetration correction in I-131 imaging following thyroid cancer
      treatment.
AB  - Whole body gamma camera images acquired after I-131 treatment for thyroid cancer
      can suffer from collimator septal penetration artefacts because of the high
      energy of the gamma photons. This results in the appearance of 'spoke' artefacts,
      emanating from regions of high activity concentration, caused by the non
      isotropic attenuation of the collimator. Deconvolution has the potential to
      reduce such artefacts, by taking into account the non-Gaussian point-spread
      function (PSF) of the system. A Richardson-Lucy deconvolution algorithm, with and
      without prior scatter-correction was tested as a method of reducing septal
      penetration in planar gamma camera images. Phantom images (hot spheres within a
      warm background) were acquired and deconvolution using a measured PSF was
      applied. The results were evaluated through region-of-interest and line profile
      analysis to determine the success of artefact reduction and the optimal number of
      deconvolution iterations and damping parameter (lambda). Without scatter
      correction, the optimal results were obtained with 15 iterations and lambda  = 
      0.01, with the counts in the spokes reduced to 20% of the original value,
      indicating a substantial decrease in their prominence. When a triple-energy
      window scatter-correction was applied prior to deconvolution, the optimal results
      were obtained with six iterations and lambda  =  0.02, which reduced the spoke
      counts to 3% of the original value. The prior application of scatter-correction
      therefore produced the best results, with a marked change in the appearance of
      the images. The optimal settings were then applied to six patient datasets, to
      demonstrate its utility in the clinical setting. In all datasets, spoke artefacts
      were substantially reduced after the application of scatter-correction and
      deconvolution, with the mean spoke count being reduced to 10% of the original
      value. This indicates that deconvolution is a promising technique for septal
      penetration artefact reduction that could potentially improve the diagnostic
      accuracy of I-131 imaging. Novelty and significance This work has demonstrated
      that scatter correction combined with deconvolution can be used to substantially
      reduce the appearance of septal penetration artefacts in I-131 phantom and
      patient gamma camera planar images, enable improved visualisation of the I-131
      distribution. Deconvolution with symmetric PSF has previously been used to reduce
      artefacts in gamma camera images however this work details the novel use of an
      asymmetric PSF to remove the angularly dependent septal penetration artefacts.

PMID- 29465415
TI  - Dose coefficients for children and young adolescents exposed to external neutron
      fields.
AB  - The risks associated with exposure to external fields of ionising radiation are
      important to quantify in order to provide guidance towards public and worker
      protection. In Publication 116 of 2010, the International Commission on
      Radiological Protection (ICRP) published adult male and female fluence-to-dose
      coefficients (henceforth referred to as dose coefficients) for external exposures
      to six types of idealised neutron fields. However, ICRP 116 dose coefficients are
      not appropriate for applications involving children due to their smaller body
      weight and stature. Our current work details dose coefficient calculations for
      children and young adolescents using the UF-NCI pediatric hybrid phantoms at all
      neutron energies considered in ICRP 116 (0.001 eV to 10 GeV); those dose
      coefficients with energy up to 150 MeV are discussed. The hybrid UF-NCI phantoms
      are divided into five separate age groups: newborn, 1, 5, 10, and 15 years. For
      these phantoms, we calculated dose coefficients for the six idealised neutron
      fields for 28 organs, two bone tissues, and the overall whole body effective
      dose. All calculations were performed using the MCNP6 radiation transport code.
      To validate our methodology, we first calculated dose coefficients for the ICRP
      adult male and female phantoms and confirmed our ability to reproduce the values
      published within ICRP 116. The same methodology was then applied to calculate
      dose coefficients for the UF-NCI pediatric phantoms. Energy-dependent trends were
      observed in the neutron dose coefficients for pediatric phantoms: below 100 keV,
      dose increases with phantom age (a proxy for body size); however, above 100 keV,
      the opposite trend was observed. Comparisons between field geometries showed
      varying trends depending on the location of the organ within the body.
      Explanations for these trends are also explored within. Our results are the first
      comprehensive set of neutron dose coefficients derived for children and young
      adolescents using the newest generation of hybrid phantoms. The primary
      application of the pediatric neutron dose coefficients presented in this work
      will be for a planned effort to update the dosimetry for the Japanese atomic bomb
      survivors.

PMID- 29465416
TI  - Ammonium-tungstate-promoted growth of boron nitride nanotubes.
AB  - Ammonium tungstate ((NH4)10W12O41 . xH2O) is a kind of oxygen-containing ammonium
      salt. The following study proves that it can be successfully used as a metal
      oxide alternative to produce boron oxide (B2O2) by oxidizing boron (B) in a
      traditional boron oxide chemical vapor deposition (BOCVD) process. This special
      oxidant promotes the simplistic fabrication of boron nitride nanotubes (BNNTs) in
      a conventional horizontal tube furnace, an outcome which may have resulted from
      its strong oxidizability. The experimental results demonstrate that the mole
      ratio of B and (NH4)10W12O41 . xH2O is a key parameter in determining the
      formation, quality and quantity of BNNTs when stainless steel is employed as a
      catalyst. We also found that Mg(NO3)2 and MgO nanoparticles (NPs) can be used as
      catalysts to grow BNNTs with the same precursor. The BNNTs obtained from the
      Mg(NO3)2 catalyst were straighter than those obtained from the MgO NP catalyst.
      This could have been due to the different physical forms of the catalysts that
      were used.

PMID- 29465417
TI  - Effect of distribution, interface property and density of hydrogel-embedded
      vertically aligned carbon nanotube arrays on the properties of a flexible solid
      state supercapacitor.
AB  - In this paper we fabricate a robust flexible solid-state supercapacitor (FSC)
      device by embedding a conductive poly(vinyl alcohol) hydrogel into aligned carbon
      nanotube (CNT) arrays. We carefully investigate the effect of distribution,
      interface properties and densification of CNTs in the gel matrix on the
      electrochemical properties of an FSC. The total electrochemical capacitance of
      the device is measured to be 227 mF cm-3 with a maximum energy density of 0.02
      mWh cm-3, which is dramatically enhanced compared with a similar device composed
      of non-parallel CNTs. Additionally, controllable in situ electrochemical
      oxidation greatly improved the compatibility between the hydrophobic CNTs and the
      hydrophilic hydrogel, which decreased the resistance of the device and introduced
      extra pseudocapacitance. After such oxidation treatment the energy storage
      ability further doubled to 430 mF cm-3 with a maximum energy density of 0.04 mWh
      cm-3 . The FSCs based on densified CNT arrays exhibited a much higher volumetric
      capacitance of 1140 mF cm-3 and a larger energy density of 0.1 mWh cm-3, with a
      large power density of 14 mW cm-3. All devices show excellent stability of
      capacitance after at least 10 000 charge-discharge cycles with a loss of less
      than 2%. These easy-to-assemble hybrid arrays thus potentially provide a new
      method for manufacturing wearable devices and implantable medical devices.

PMID- 29465418
TI  - Distinguishing Majorana bound states and Andreev bound states with microwave
      spectra.
AB  - Majorana fermions are a fascinating and not yet confirmed quasiparticles in
      condensed matter physics. Here we propose using microwave spectra to distinguish
      Majorana bound states (MBSs) from topological trivial Andreev bound states. By
      numerically calculating the transmission and Zeeman field dependence of the many
      body excitation spectrum of a 1D Josephson junction, we find that the two kinds
      of bound states have distinct responses to variations in the related parameters.
      Furthermore, the singular behaviors of the MBSs spectrum could be attributed to
      the robust fractional Josephson coupling and nonlocality of MBSs. Our results
      provide a feasible method to verify the existence of MBSs and could accelerate
      its application to topological quantum computation.

PMID- 29465419
TI  - Assessment of PCXMC for patients with different body size in chest and abdominal
      x ray examinations: a Monte Carlo simulation study.
AB  - A PC Program for x ray Monte Carlo (PCXMC) has been used to calculate organ doses
      in patient dosimetry and for the exposure assessment in epidemiological studies
      of radiogenic health related risks. This study compared the dosimetry from using
      the built-in stylized phantoms in the PCXMC to that of a newer hybrid phantom
      library with improved anatomical realism. We simulated chest and abdominal x ray
      projections for 146 unique body size computational phantoms, 77 males and 69
      females, with different combinations of height (125-180 cm) and weight (20-140
      kg) using the built-in stylized phantoms in the PCXMC version 2.0.1.4 and the
      hybrid phantom library using the Monte Carlo N-particle eXtended transport code
      2.7 (MCNPX). Unfortunately, it was not possible to incorporate the hybrid phantom
      library into the PCXMC. We compared 14 organ doses, including dose to the active
      bone marrow, to evaluate differences between the built-in stylized phantoms in
      the PCXMC and the hybrid phantoms (Cristy and Eckerman 1987 Technical Report
      ORNL/TM-8381/V1, Oak Ridge National Laboratory, Eckerman and Ryman 1993 Technical
      Report 12 Oak Ridge, TN, Geyer et al 2014 Phys. Med. Biol. 59 5225-42). On
      average, organ doses calculated using the built-in stylized phantoms in the PCXMC
      were greater when compared to the hybrid phantoms. This is most prominent in AP
      abdominal exams by an average factor of 2.4-, 2.8-, and 2.8-fold for the 10-year
      old, 15-year-old, and adult phantoms, respectively. For chest exams, organ doses
      are greater by an average factor of 1.1-, 1.4-, and 1.2-fold for the 10-year-old,
      15-year-old, and adult phantoms, respectively. The PCXMX, due to its ease of use,
      is often selected to support dosimetry in epidemiological studies; however, it
      uses simplified models of the human anatomy that fail to account for variations
      in body morphometry for increasing weight. For epidemiological studies that use
      PCXMC dosimetry, associations between radiation-related disease risks and organ
      doses may be underestimated, and to a greater degree in pediatric, especially
      obese pediatric, compared to adult patients.

PMID- 29465420
TI  - Pathologic Features of Infectious Gastritis.
AB  - This manuscript presents a review of infectious causes of gastritis aimed at the
      practicing anatomic pathologist. We shall highlight unique histologic findings
      and clinical attributes that will assist those analyzing endoscopically obtained
      mucosal biopsies of the stomach or resection specimens.

PMID- 29465421
TI  - Molecular and Metabolic Basis of Clear Cell Carcinoma of the Kidney.
AB  - Renal cell carcinoma (RCC) is a heterogenous group of tumors, >70% of which
      belong to the category of clear cell carcinoma. In recent years, crucial advances
      have been made in our understanding of the molecular and metabolic basis of clear
      cell carcinoma. This tumor manifests significant alterations in the cellular
      metabolism, so that the tumor cells preferentially induce the hypoxia response
      pathway using aerobic glycolysis, rather than the normal oxidative
      phosphorylation for energy. Most of the clear cell carcinomas (sporadic as well
      as familial) have mutations and deletions in the VHL gene located at 3p (p3.25).
      Normally, pVHL plays a crucial role in the proteasomal degradation of hypoxia
      inducible factors (HIF)1 and HIF2. Lack of a functioning pVHL owing to genetic
      alterations results in stabilization and accumulation of these factors, which
      promotes cell growth, cell proliferation, and angiogenesis, contributing to a
      neoplastic phenotype. Several other genes normally located adjacent to VHL (BAP1,
      SETD2, PBRM1) may also be lost. These are tumor suppressor genes whose loss not
      only plays a role in carcinogenesis but may also influence the clinical course of
      these neoplasms. In addition, interaction among a variety of other genes located
      at several different chromosomes may also play a role in the genesis and
      progression of clear cell carcinoma.

PMID- 29465422
TI  - Elevated Postmortem Vitreous Sodium and Chloride Level in a Salt Water Drowning
      Death During Self-Contained Underwater Breathing Apparatus Diving With Diving
      Mask in Place: Case Report.
AB  - Elevation of postmortem vitreous sodium and chloride (PMVSC) levels in salt water
      drowning (SWD) is hypothesized to result from electrolyte changes in blood from
      salt water inhalation/ingestion during drowning. After approximately 1 hour after
      death, electrolytes may diffuse into the vitreous humor via the eye coverings.
      This hypothesis was based on a study where bovine eyeballs were immersed in salt
      water. There is no human study that could confirm that SWD would result in an
      initial elevation of PMVSC with no effects from immersion. We present an SWD
      during self-contained underwater breathing apparatus diving in which the face
      mask remained in its correct position while the deceased was underwater. The face
      mask would have prevented the orbits from being in direct contact with salt water
      and therefore stopped any effects of immersion on PMVSC. The PMVSC was 294
      mmol/L, above control levels, and the reported cut-off of 259 mmol/L for a
      diagnosis SWD. The elevated PMVSC would unlikely be owing to immersion but SWD.
      This case report supports the observation that during SWD PMVSC would initially
      increase from salt water inhalation and ingestion and not from immersion.

PMID- 29465423
TI  - Patient Perceptions of Minimally Invasive Versus Open Spine Surgery.
AB  - STUDY DESIGN: Prospective questionnaire. OBJECTIVE: To describe patient
      perceptions of minimally invasive spine (MIS) versus open surgery, and to
      determine which factors are most heavily considered by the patient when choosing
      between approaches. SUMMARY OF BACKGROUND DATA: MIS surgery has increased in
      popularity due to proposed advantages in the perioperative and immediate
      postoperative periods. However, patient preferences and understanding with regard
      to the differences between MIS and open surgery have not been elucidated.
      MATERIALS AND METHODS: An anonymous questionnaire consisting of 30 questions was
      administered to patients scheduled to see either an MIS surgeon or an open spine
      surgeon for a clinical evaluation from 2016 to 2017. Six questions asked about
      patient demographics and medical history. Nine questions asked respondents to
      rate the importance of several criteria when deciding between MIS and open
      surgery. In total, 15 multiple choice and free response questions asked
      respondents about their perceptions of MIS versus open surgery with regard to
      surgical and physician characteristics. RESULTS: In total, 326 patients completed
      the survey. The 3 most important criteria for patients when choosing between open
      and MIS surgery were: long-term outcomes, surgeon's recommendation, and
      complication risk. When compared with MIS surgery, the majority of patients
      perceived open surgery to be more painful (83.8%), have increased complication
      risk (78.5%), have increased recovery time (89.3%), have increased costs (68.1%),
      and require heavier sedation (62.6%). If required to have spine surgery in the
      future, the majority of both patient groups would prefer a minimally invasive
      approach (80.0%). CONCLUSIONS: Long-term outcomes, surgeon's recommendation, and
      complication risk were the most important criteria identified by patients when
      choosing between open and MIS surgery. Patients also perceived MIS surgery to
      have advantages over open surgery with regard to postoperative pain, complication
      risk, recovery time, cost, and anesthesia requirement. Most patients seem to
      prefer a minimally invasive approach to their treatment.

PMID- 29465424
TI  - Nutritional approach to preeclampsia prevention.
AB  - PURPOSE OF REVIEW: Although not fully understood, the physiopathology of
      preeclampsia is thought to involve an abnormal placentation, diffuse endothelial
      cell dysfunction and increased systemic inflammation. As micronutrients play a
      key role in placental endothelial function, oxidative stress and expression of
      angiogenic factors, periconceptional micronutrient supplementation has been
      proposed to reduce the risk of preeclampsia. However, recent studies reported
      conflicting results. RECENT FINDINGS: Calcium intake (>1 g/day) may reduce the
      risk of preeclampsia in women with low-calcium diet. Data from recently updated
      Cochrane reviews did not support routine supplementation of vitamins C, E or D
      for either the prevention or treatment of preeclampsia. Evidences are also poor
      to support zinc or folic acid supplementation for preeclampsia prevention. Dark
      chocolate, flavonoid-rich food, and long-chain polyunsaturated fatty acids might
      also be candidates for prevention of preeclampsia. SUMMARY: Through antioxidant,
      anti-inflammatory or vasoactive proprieties, micronutrients are good candidates
      for preeclampsia prevention. Calcium supplementation is recommended to prevent
      preeclampsia in women with low-calcium intake. Despite positive clinical and in
      vitro data, strong evidence to support periconceptional supplementation of other
      micronutrients for preeclampsia risk-reduction is still lacking. Further studies
      are also needed to evaluate the benefit of nutritional supplementation such as
      chocolate and long-chain polyunsaturated fatty acids.

PMID- 29465425
TI  - Optimization of nutrition during allogeneic hematologic stem cell
      transplantation.
AB  - PURPOSE OF REVIEW: Malnutrition before and during hematopoietic stem cell
      transplantation (HSCT) is an independent risk factor for mortality in patients
      undergoing hematopoietic stem cell transplantation. Yet, optimal use of
      nutritional support to improve outcomes remains controversial. Our aim was to do
      an up-to-date literature review regarding nutritional therapy in allogeneic HSCT,
      the neutropenic diet and the use of immunonutrients. RECENT FINDINGS: Several
      observational studies find malnutrition to be associated with poor outcome,
      increased complications and lower overall survival. There are, however, few
      interventional trials proving the benefits of nutritional therapy in this
      population compared with no nutritional treatment. Regarding routes of treatment,
      studies suggested that parenteral nutrition is associated with higher risk for
      complications compared with enteral nutrition. Whether the use of specific
      formulas, such as immunonutrition, has a beneficial effect on clinical outcome is
      not established yet. Strict use of neutropenic diets did not show a reduction in
      infection risk and clinical outcome, and can no longer be recommended. SUMMARY:
      Our updated search confirms that malnutrition is a strong negative predictor for
      outcome, yet optimal use of nutritional interventions to prevent or treat
      malnutrition remains ill-defined. There is need for larger randomized trials to
      better address these issues in the future.

PMID- 29465426
TI  - Advances in molecular diagnosis and therapeutics in nephrotic syndrome and focal
      and segmental glomerulosclerosis.
AB  - PURPOSE OF REVIEW: The widespread adoption of next-generation sequencing by
      research and clinical laboratories has begun to uncover the previously unknown
      genetic basis of many diseases. In nephrology, one of the best examples of this
      is seen in focal and segmental glomerulosclerosis (FSGS) and nephrotic syndrome.
      We review advances made in 2017 as a result of human and molecular genetic
      studies as it relates to FSGS and nephrotic syndrome. RECENT FINDINGS: There are
      more than 50 monogenic genes described in steroid-resistant nephrotic syndrome
      and FSGS, with seven reported in 2017. In individuals presenting with FSGS or
      nephrotic syndrome before or at the age of 18 years, the commonest genes in which
      a mutation is found continues to be limited to only a few including NPHS1 and
      NPHS2 based on multiple studies. For FSGS or nephrotic syndrome that presents
      after 18 years, mutations in COl4A3/4/5, traditionally associated with Alport
      syndrome, are increasingly being reported. Despite the extensive genetic
      heterogeneity in FSGS, there is evidence that some of these genes converge onto
      common pathways. There are also reports of in-vivo models exploring
      apolipoprotein 1 biology, variants in which account for part of the increased
      risk of nondiabetic kidney disease in African-Americans. Finally, genetic testing
      has several clinical uses including clarification of diagnosis and treatment;
      identification of suitable young biologic relatives for kidney donation; and
      preimplantation genetic diagnosis. CRISPR gene editing is currently an
      experimental tool only, but the recent reports of excising mutations in embryos
      could be a therapeutic option for individuals with any monogenic disorder in the
      future. SUMMARY: Sequencing efforts are bringing novel variants into
      investigation and directing the efforts to understand how these lead to disease
      phenotypes. Expanding our understanding of the genetic basis of health and
      disease processes is the necessary first step to elaborate the repertoire of
      therapeutic agents available for patients with FSGS and nephrotic syndrome.

PMID- 29465427
TI  - Dihydrotestosterone and cancer risk.
AB  - PURPOSE OF REVIEW: Androgens have been implicated in prostate growth; however,
      the role of androgens in prostate cancer development is not clear. Furthermore,
      studies suggest a role for androgens in female-hormone-dependent cancers and
      common nonhormone dependent cancers. This study aims to review key studies and
      more recent studies of dihydrotestosterone (DHT) and cancer risk. RECENT
      FINDINGS: Epidemiological studies are reassuring as they have not associated
      endogenous androgens with prostate cancer risk. Intraprostatic regulation of DHT
      is becoming recognized as an important area of research to clarify the role of
      DHT in prostate cancer development. In females, further understanding of
      intracrine regulation of sex hormones and interactions between androgens and
      estrogens in influencing breast and endometrial cancer risk are required. Studies
      show a signal for DHT in modulating lung and colorectal cancer growth; however,
      research in this area is relatively scarce and further studies are required to
      clarify these associations. SUMMARY: Although concerns of prostate cancer risk
      remain, there is also potential for androgens to modulate the growth and
      development of other common cancers. Further research is required as this may
      have clinical implications.

PMID- 29465428
TI  - Recent advances in radiation oncology: multimodal targeting of high risk and
      recurrent prostate cancer.
AB  - PURPOSE OF REVIEW: The overview summarizes recent developments in radiation
      oncology for high risk and recurrent prostate cancer. RECENT FINDINGS: A number
      of well known phase III prostate hypofractionated radiation therapy (HFxRT)
      trials were finally published with long-term follow-ups. These trials demonstrate
      patterns of equivalent tumor control with several showing worse toxicity rates.
      The ASCENDE-RT randomized trial demonstrated the superiority of brachytherapy
      boost in intermediate and high-risk prostate cancer. Important randomized trials
      show a clear benefit to androgen deprivation therapy (ADT) in both intermediate
      risk prostate cancer and postprostatectomy patients with rising PSA. Finally, the
      first randomized trial of metastasis-directed therapy showed a delay in time to
      ADT and biochemical failures in oligometastatic prostate cancer. SUMMARY: The use
      of brachytherapy boost in high-risk disease and ADT in locally recurrent cancer
      after prostatectomy are practice changing given the magnitude of benefit seen in
      the randomized trials. The benefit of metastasis-directed therapy in
      oligometastatic prostate cancer must be validated in a larger randomized trial.
      However, hypofractionated radiation therapy requires further long-term follow-up
      so that late toxicity risk can be accurately assessed before it becomes a
      standard of care in prostate cancer.

PMID- 29465430
TI  - New paradigms for organ allocation and distribution in liver transplantation.
AB  - PURPOSE OF REVIEW: The 'Final Rule,' issued by the Health Resources and Service
      Administration in 2000, mandated that liver allocation policy should be based on
      disease severity and probability of death, and - among other factors - should be
      independent of a candidate's residence or listing. As a result, the Organ
      Procurement Transplantation Network/United Network for Organ Sharing (UNOS) has
      explored policy changes addressing geographic disparities without compromising
      outcomes. RECENT FINDINGS: Major paradigm shifts are underway in U.S. liver
      allocation policy. New hepatocellular carcinoma exception policy incorporates
      tumor characteristics associated with posttransplantation outcomes, whereas a
      National Liver Review Board will promote a standardized process for awarding
      exception points. Meanwhile, following extensive debate, new allocation policy
      aims to reduce geographic disparity by broadening sharing to the UNOS region and
      150-mile circle around the donor hospital for liver transplant candidates with a
      calculated model for end-stage liver disease score at least 32. Unnecessary organ
      travel will be reduced by granting 3 'proximity points' to candidates within the
      same donation service area (DSA) as a liver donor or within 150 nautical miles of
      the donor hospital, regardless of DSA or UNOS region. SUMMARY: This review
      provides an evaluation of major policy changes in liver allocation from 2016 to
      2018.

PMID- 29465429
TI  - Advances in prostate-specific membrane antigen PET of prostate cancer.
AB  - PURPOSE OF REVIEW: In recent years, a large number of reports have been published
      on prostate-specific membrane antigen (PSMA)/PET in prostate cancer (PCa). This
      review highlights advances in PSMA PET in PCa during the past year. RECENT
      FINDINGS: PSMA PET/computed tomography (CT) is useful in detection of biochemical
      recurrence, especially at low prostate-specific antigen (PSA) values. The
      detection rate of PSMA PET is influenced by PSA level. For primary PCa, PSMA
      PET/CT shows promise for tumour localization in the prostate, especially in
      combination with multiparametric MRI (mpMRI). For primary staging, PSMA PET/CT
      can be used in intermediate and high-risk PCa. Intraoperative PSMA radioligand
      guidance seems promising for detection of malignant lymph nodes. While the use of
      PSMA PET/MRI in primary localized disease is limited to high and intermediate
      risk patients and localized staging, in the recurrence setting, PET/MRI can be
      particularly helpful when the lesions are subtle. PSMA PET/CT is superior to
      choline PET/CT and other conventional imaging modalities. SUMMARY: Molecular
      imaging with PSMA PET continues to pave the way for personalized medicine in
      PCa.However, large prospective clinical studies are still needed to fully
      evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa.

PMID- 29465431
TI  - Noncirrhotic portal hypertension.
AB  - PURPOSE OF REVIEW: Noncirrhotic portal hypertension represents a heterogeneous
      group of liver disorders that is characterized by portal hypertension in the
      absence of cirrhosis. The purpose of this review is to serve as a guide on how to
      approach a patient with noncirrhotic portal hypertension with a focus on recent
      developments. RECENT FINDINGS: Recent studies pertaining to noncirrhotic portal
      hypertension have investigated aetiological causes, mechanisms of disease,
      noninvasive diagnostic modalities, clinical characteristics in the paediatric
      population and novel treatment targets. SUMMARY: Noncirrhotic portal hypertension
      is an underappreciated clinical entity that can be difficult to diagnosis without
      a healthy suspicion. Diagnosis then relies on a comprehensive understanding of
      the causes and clinical manifestations of this disease, as well as a careful
      interpretation of the liver biopsy. Noninvasive approaches to diagnosis may play
      a significant role moving forward in this disease. Treatment in NCPH remains
      largely targeted at the individual sequalae of portal hypertension.

PMID- 29465433
TI  - Emerging targets for reprograming the immune response to promote repair and
      recovery of function after spinal cord injury.
AB  - PURPOSE OF REVIEW: In adult mammals, a traumatic spinal cord injury (SCI) elicits
      a chronic unregulated neuroinflammatory response accompanied by seemingly
      paradoxical suppression of systemic immunity. These SCI-induced changes in immune
      function contribute to poor neurological outcomes and enhanced morbidity or
      mortality. Nonspecific anti-inflammatory or proinflammatory therapies are
      ineffective and can even worsen outcomes. Therefore, recent experimental SCI
      research has advanced the understanding of how neuroimmune cross-talk contributes
      to spinal cord and systemic pathology. RECENT FINDINGS: It is now appreciated
      that the immune response caused by injury to the brain or spinal cord encompasses
      heterogeneous elements that can drive events on the spectrum between exacerbating
      pathology and promoting tissue repair, within the spinal cord and throughout the
      body. Recent novel discoveries regarding the role and regulation of soluble
      factors, monocytes/macrophages, microRNAs, lymphocytes and systemic immune
      function are highlighted in this review. SUMMARY: A more nuanced understanding of
      how the immune system responds and reacts to nervous system injury will present
      an array of novel therapeutic opportunities for clinical SCI and other forms of
      neurotrauma.

PMID- 29465434
TI  - The Five-Year Clinical and Angiographic Follow-Up Outcomes of Intracoronary
      Transfusion of Circulation-Derived CD34+ Cells for Patients With End-Stage
      Diffuse Coronary Artery Disease Unsuitable for Coronary Intervention-Phase I
      Clinical Trial.
AB  - OBJECTIVES: This study investigated the clinical and angiographic long-term
      outcomes of intracoronary transfusion of circulation-derived CD34+ cells for
      patients with end-stage diffuse coronary artery disease unsuitable for coronary
      intervention. DESIGN AND SETTING: A single-center prospective randomized double
      blinded phase I clinical trial. Thirty-eight patients undergoing CD34+ cell
      therapy were allocated into groups 1 (1.0 * 10 cells/each vessel; n = 18) and 2
      (3.0 * 10 cells/each vessel; n = 20). PATIENTS: Those with end-stage diffuse
      coronary artery disease were unsuitable for percutaneous and surgical coronary
      revascularization. INTERVENTIONS: Intracoronary delivery of circulation-derived
      CD34+ cells. MEASUREMENTS AND MAIN RESULTS: We prospectively evaluated long-term
      clinical and echocardiographic/angiographic outcomes between survivors and
      nonsurvivors. By the end of 5-year follow-up, the survival rate and major adverse
      cardio/cerebrovascular event were 78.9% (30/38) and 36.8% (14/38), respectively.
      During follow-up period, 31.6% patients (12/38) received coronary stenting for
      reason of sufficient target vessel size grown-up after the treatment. Endothelial
      function was significantly reduced in the nonsurvivors than the survivors (p =
      0.039). Wimasis image analysis of angiographic findings showed that the
      angiogenesis was significantly and progressively increased from baseline to 1 and
      5 years (all p < 0.001). The 3D echocardiography showed left ventricular ejection
      fraction increased from baseline to 1 year and then remained stable up to 5
      years, whereas left ventricular chamber diameter exhibited an opposite pattern to
      left ventricular ejection fraction among the survivors. The clinical scores for
      angina and heart failure were significantly progressively reduced from baseline
      to 1 and 5 years (all p < 0.001). CONCLUSIONS: CD34+ cell therapy for end-stage
      diffuse coronary artery disease patients might contribute to persistently long
      term effects on improvement of left ventricular function, angina/heart failure,
      and amelioration of left ventricular remodeling.

PMID- 29465435
TI  - Clinical manifestations of sickle cell disease in India: misconceptions and
      reality.
AB  - PURPOSE OF REVIEW: In the past, milder clinical manifestations of sickle cell
      disease (SCD) have been described from India. However, recent data from some
      parts of India suggest that the severity of the disease can be compared to that
      of African phenotypes. This review therefore describes the varied clinical
      manifestation of SCD, the success of newborn screening programme, prenatal
      diagnosis and low dose hydroxyurea therapy in India. RECENT FINDINGS: The varied
      clinical manifestations such as anemia, vaso-occlusive crisis, acute chest
      syndrome, renal involvement, stroke and so on vary from one part of the country
      to the other and also among different communities of India. Strategies for
      improving quality of life and controlling of SCD have been suggested. Certain
      factors other than genetics also play an important role in clinical manifestation
      of the disorder. SUMMARY: The clinical diversity of SCD is described. The natural
      history of SCD in India is unfolding from newborn screening programme. The use of
      low-dose hydroxy urea therapy both in adults and children has brought down the
      incidences of crisis and provides great relief to the patients. The tailor-made
      programme for India as regards the control and management has been discussed.

PMID- 29465432
TI  - Mechanisms for lesion localization in neuromyelitis optica spectrum disorders.
AB  - PURPOSE OF REVIEW: Neuromyelitis optica spectrum disorders (NMOSD) are severe
      inflammatory diseases of the central nervous system (CNS), with the presence of
      aquaporin 4 (AQP4)-specific serum antibodies in the vast majority of patients,
      and with the presence of myelin oligodendrocyte glycoprotein (MOG)-specific
      antibodies in approximately 40% of all AQP4-antibody negative NMOSD patients.
      Despite differences in antigen recognition, the preferred sites of lesions are
      similar in both groups of patients: They localize to the spinal cord and to the
      anterior visual pathway including retina, optic nerves, chiasm, and optic tracts,
      and - to lesser extent - also to certain predilection sites in the brain. RECENT
      FINDINGS: The involvement of T cells in the formation of NMOSD lesions has been
      challenged for quite some time. However, several recent findings demonstrate the
      key role of T cells for lesion formation and localization. Studies on the
      evolution of lesions in the spinal cord of NMOSD patients revealed a striking
      similarity of early NMOSD lesions with those observed in corresponding T-cell
      induced animal models, both in lesion formation and in lesion localization.
      Studies on retinal abnormalities in NMOSD patients and corresponding animals
      revealed the importance of T cells for the very early stages of retinal lesions
      which eventually culminate in damage to Muller cells and to the retinal nerve
      fiber layer. Finally, a study on cerebrospinal fluid (CSF) barrier pathology
      demonstrated that NMOSD immunopathology extends beyond perivascular astrocytic
      foot processes to include the pia, the ependyma, and the choroid plexus, and that
      diffusion of antibodies from the CSF could further influence lesion formation in
      NMOSD patients. SUMMARY: The pathological changes observed in AQP4-antibody
      positive and MOG-antibody positive NMOSD patients are strikingly similar to those
      found in corresponding animal models, and many mechanisms which determine lesion
      localization in experimental animals seem to closely reflect the human situation.

PMID- 29465436
TI  - Orbital exenteration for sinonasal malignancies: indications, rehabilitation and
      oncologic outcomes.
AB  - PURPOSE OF REVIEW: Review the recent literature regarding the management of
      orbital invasion in sinonasal malignant tumors. RECENT FINDINGS: There is a
      recent trend in preserving the orbit in cases of minimal invasion of periosteum
      and limited periorbit involvement, as well as in presence of good response to
      neoadjuvant chemotherapy, mainly in squamous cell carcinoma and neuroendocrine
      histologies. SUMMARY: The decision about orbital exenteration in cases of
      sinonasal malignancies is facilitated if the patient already has clear clinical
      signs of intraconal invasion such as visual loss, restriction of ocular mobility
      or infiltration of the eyeglobe. However, in borderline situations, confirmation
      of orbital involvement should be performed intraoperatively. In selected cases
      with minimal orbital invasion without functional compromise, orbit sparing
      surgery can be done with acceptable oncological outcomes.

PMID- 29465437
TI  - Perspectives on voice treatment for unilateral vocal fold paralysis.
AB  - PURPOSE OF REVIEW: Unilateral vocal fold paralysis (UVFP) is a common cause of
      neurogenic dysphonia resulting in glottal insufficiency. To restore glottal
      sufficiency and reduce the presenting dysphonia, treatment involving either
      surgical intervention, voice therapy or a combination of the two is typically
      provided. Currently, there is no consensus for the most effective voice treatment
      for UVFP. This results in an inability to compare current studies, and a lack of
      treatment effectiveness for the management of UVFP. This study aims to review the
      most recent literature for the management of dysphonia due to UVFP to establish
      the current evidence base for voice treatment options. RECENT FINDINGS: There was
      found to be a lack of consistency in the rationale, selection and timing of the
      surgical intervention and/or voice therapy being provided for patients with UVFP.
      SUMMARY: Further consensus is required for the rationale and selection of voice
      treatment prescriptions for the management of UVFP in order to improve treatment
      effectiveness and voice outcomes in patients with UVFP.

PMID- 29465438
TI  - The evolving role of percutaneous ventricular assist devices in high-risk cardiac
      patients.
AB  - The Impella is a mechanical circulatory support device that supports ventricular
      function. Since 2008, when the first Impella device received Food and Drug
      Administration clearance, its use has become increasingly prevalent. A variety of
      Impella devices are available, and are differentiated by size, power, and
      insertion techniques. These versions of the Impella have been used in a multitude
      of clinical scenarios, both emergent and elective, including high-risk coronary
      interventions, acute myocardial infarction complicated by cardiogenic shock,
      decompensated left and right heart failure, high-risk ventricular tachycardia
      ablations, and aortic valvuloplasty. However, the available evidence supporting
      its use is less than robust, primarily consisting of case reports and registries,
      with a limited number of randomized-controlled trials comparing the Impella with
      the intra-aortic balloon pump. Although these trials show that the Impella
      provides better hemodynamic support compared with the intra-aortic balloon pump,
      they failed to show a survival benefit for the Impella. This finding may have a
      number of explanations, foremost the inherent difficulty of selecting appropriate
      patients for trials that are conducted in extreme clinical settings. In this
      study, we discuss the mechanism of the Impella and the different types of Impella
      devices available, and review the medical literature for evidence of its efficacy
      in treating cardiac patients. Although the Impella has become ubiquitous in
      certain markets, such as in the USA, it has yet to be a part of the standard of
      care for patients in Israel.

PMID- 29465439
TI  - Intestinal re-transplantation: indications, techniques and outcomes.
AB  - PURPOSE OF REVIEW: The field of intestinal transplantation has shown significant
      growth and has become the gold standard therapy for patients that suffer from the
      complications of total parenteral nutrition due to irreversible intestinal
      failure. In the early years of intestinal transplant, retransplantation was
      associated with extremely high morbidity and mortality. The purpose of this
      review is to summarize recent encouraging reports, showing significant
      improvement in outcomes after intestinal retransplantation. RECENT FINDINGS:
      Recent studies at large volume centers have reported significant progress in
      patient and graft survival after intestinal retransplantation. Recent literature
      described the most common indications for retransplantation, surgical techniques,
      timing of graft enterectomy, immunologic monitoring, and complications.
      Improvement in outcomes due to advances in immunosuppression management and the
      importance of liver-containing grafts are also described. SUMMARY: Improving
      early to midterm patient and graft survival has made consideration for intestinal
      retransplantation even more necessary. Current clinical evidence supports the
      benefit of intestinal retransplantation in well selected recipients. Initial
      immunosuppression protocols, technical modifications, proper timing of
      enterectomy, and improved infectious disease monitoring have contributed to
      improved outcomes.

PMID- 29465440
TI  - Obesity management in the liver transplant recipient: the role of bariatric
      surgery.
AB  - PURPOSE OF REVIEW: The epidemic of obesity is having a marked impact on liver
      transplant candidates and recipients, and optimal approach for the obese liver
      transplant patient is not yet defined. The current review summarizes the role of
      bariatric surgery in obese liver transplant patients. RECENT FINDINGS: NASH is
      now the second most common indication for listing for liver transplantation and
      is the third most common reason for patients undergoing liver transplantation.
      Recent reports of outcomes for obese recipients demonstrate satisfactory patient
      and graft survival, though complication rates may be higher. The impact of weight
      loss on long-term health in the nontransplant population, including those with
      liver disease, has been demonstrated, though less in known on the impact for
      weight loss and bariatric surgery for liver transplant recipients. SUMMARY:
      Obesity-related liver disease has become one of the most common indications for
      liver transplantation and further research is needed to determine the role of
      bariatric surgery in the optimal management of this population.

PMID- 29465441
TI  - Letter to the Editor Involving the Article "Comparison Between Corticosteroids
      and Lidocaine Injection in the Treatment of Tennis Elbow: A Randomized, Double
      Blinded, Controlled Trial".

PMID- 29465442
TI  - Comparison Between Corticosteroid and Lidocaine Injection in the Treatment of
      Tennis Elbow: A Randomized, Double-Blinded, Controlled Trial.

PMID- 29465443
TI  - Outcome Trends of Adult Cancer Patients Receiving Inpatient Rehabilitation: A 13
      Year Review.
AB  - OBJECTIVE: This study describes characteristics and trends of inpatient
      rehabilitation among cancer patients within the United States over a 13-yr
      period. DESIGN: This was a retrospective study of data from the Uniform Data
      System for Medical Rehabilitation from 2002 to 2014. Patients older than 17 yrs
      admitted to inpatient rehabilitation facilities with a diagnosis of malignant
      cancer were included. Trends of rehabilitation outcomes including length of stay,
      Functional Independence Measure (FIM) Instrument scores, and discharge location
      were examined. RESULTS: Data from 115,570 cancer patients were evaluated. Mean
      age was 66 +/- 14 yrs and 49% were women. Mean length of stay decreased over time
      (2002: 14 days to 2014: 13 days; P < 0.0005). Patient's admission total FIM
      scores decreased over time (2002: 68 +/- 18 to 2014: 61 +/- 16; P < 0.0005). The
      FIM change score increased over time (2002: 19 +/- 16 to 2014: 25 +/- 17; P <
      0.0005). The greatest significant functional gains occurred in self care and
      transfers. Most patients (>70%) were discharged to the community. CONCLUSIONS:
      Cancer patients receiving acute inpatient rehabilitation demonstrated significant
      improvements in functional outcomes from admission to discharge. Cancer patients
      became more independent in important activities of daily living, thereby
      potentially reducing caregiver burden and ensuring safer discharges back to the
      community. This study suggests potential benefit of inpatient rehabilitation for
      appropriate cancer patients.

PMID- 29465444
TI  - Effects of Anodal Transcranial Direct Current Stimulation on Somatosensory
      Recovery After Stroke: A Randomized Controlled Trial.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of anodal
      transcranial direct current stimulation over the primary somatosensory cortex on
      the recovery of somatosensation, motor function, and the activities of daily
      living in patients with subacute stroke. DESIGN: This study was a prospective,
      randomized sham controlled, double-blinded study. Patients with subacute stroke
      having somatosensory deficits (N = 24) were enrolled and assigned randomly to the
      anodal and sham stimulation groups. Patients received 10 consecutive anodal or
      sham transcranial direct current stimulations over the primary somatosensory
      cortex on the side of the stroke lesion. Before and after each stimulation
      session, Nottingham sensory assessments, Semmes Weinstein monofilaments
      examination, and manual function tests were performed, and modified Brunnstrom
      classification, modified Barthel index, and functional ambulation categories were
      assessed. RESULTS: Although there was no clear significant difference between the
      two groups, when the changes from baseline to posttreatment evaluation were
      compared between the groups, a partially significant improvement was observed in
      the anodal stimulation group compared with the sham stimulation group.
      Interestingly, the tactile sensation of the unaffected side also improved.
      Moreover, the greater improvement in activities of daily living function was
      observed in the anodal stimulation group too. CONCLUSION: Anodal transcranial
      direct current stimulation over the primary somatosensory cortex may be a useful
      adjuvant therapy for the recovery of somatosensation and activities of daily
      living function in patients with sensory deficits after stroke.

PMID- 29465445
TI  - Regorafenib-Associated Fatigue: A Systematic Review and Meta-analysis.

PMID- 29465447
TI  - Extracellular vesicles in cardiovascular homeostasis and disease.
AB  - PURPOSE OF REVIEW: Extracellular vesicles have emerged as one of the most
      important means through which cells interact with each other and the
      extracellular environment, but extracellular vesicle research remains challenging
      due to their small size, limited amount of material required for traditional
      molecular biology assays and inconsistency in the methods of their isolation. The
      advent of new technologies and standards in the field, however, have led to
      increased mechanistic insight into extracellular vesicle function. Herein, the
      latest studies on the role of extracellular vesicles in cardiovascular physiology
      and disease are discussed. RECENT FINDINGS: Extracellular vesicles help control
      cardiovascular homeostasis and remodelling by mediating communication between
      cells and directing alterations in the extracellular matrix to respond to changes
      in the environment. The message carried from the parent cell to extracellular
      space can be intended for both local (within the same tissue) and distal
      (downstream of blood flow) targets. Pathological cargo loaded within
      extracellular vesicles could further result in various diseases. On the contrary,
      new studies indicate that injection of extracellular vesicles obtained from
      cultured cells into diseased tissues can promote restoration of normal tissue
      function. SUMMARY: Extracellular vesicles are an integral part of cell and tissue
      function, and harnessing the properties inherent to extracellular vesicles may
      provide a therapeutic strategy to promote tissue regeneration.

PMID- 29465448
TI  - Learning Through Boundary Crossing: Professional Identity Formation of
      Pharmacists Transitioning to General Practice in the Netherlands.
AB  - PURPOSE: To unravel boundary crossing as it relates to professional identity
      formation in pharmacists transitioning from a community pharmacy to working as
      nondispensing clinical pharmacists in general practice, with the aim of
      optimizing their education. METHOD: This was a multiple-case study, including two
      stage interviews, peer feedback, and individual reflection, that collected data
      in 2014-2016 from eight clinical pharmacists working in general practice in the
      Netherlands. These pharmacists acted-without a workplace role model-as
      pharmaceutical care providers in general practices during a 15-month training
      program. In within-case and cross-case analysis, data were collected regarding
      pharmacists' role development in practice and perceptions of learning processes,
      and examined through the lens of professional identity formation and boundary
      crossing. RESULTS: Analysis of data collected during and after the training
      program demonstrated that the clinical pharmacists who applied the learning
      mechanisms of reflection and transformation developed a patient-care-oriented
      professional identity. Some clinical pharmacists, who learned mainly through the
      mechanism of identification, did not integrate the new patient-care-oriented role
      into their professional identity. They felt that their workplace provided limited
      opportunities for reflection and transformation. Learning with peers on formal
      training days was seen as highly valuable for professional identity formation; it
      counterbalanced the lack of a role model in the workplace. CONCLUSIONS:
      Professional identity formation in the transition from community pharmacist to
      clinical pharmacist in general practice benefited from reflective, on-the-job
      training. This permitted transformative, boundary-crossing learning with peers
      and supported professional identity formation oriented to providing practice
      based pharmaceutical care.

PMID- 29465446
TI  - Current Practices and Attitudes Regarding Use of Inhaled Nitric Oxide in the
      NICU: Results From a Survey of Members of the National Association of Neonatal
      Nurse Practitioners.
AB  - BACKGROUND: Excessive supplemental oxygen exposure in the neonatal intensive care
      unit (NICU) can be associated with oxygen-related toxicities, which can lead to
      negative clinical consequences. Use of inhaled nitric oxide (iNO) can be a
      successful strategy for avoiding hyperoxia in the NICU. iNO selectively produces
      pulmonary vasodilation and has been shown to improve oxygenation parameters
      across the spectrum of disease severity, from mild to very severe, in neonates
      with hypoxic respiratory failure associated with persistent pulmonary
      hypertension of the newborn. PURPOSE: An online survey was conducted among
      members of the National Association of Neonatal Nurse Practitioners to gain
      insight into the level of understanding and knowledge among neonatal nurse
      practitioners (NNPs) about optimizing supplemental oxygen exposure and the use of
      iNO in the NICU setting. RESULTS: Of 937 NNP respondents, 51% reported that their
      healthcare team typically waits until the fraction of inspired oxygen level is
      0.9 or more before adding iNO in patients not responding to oxygen ventilation
      alone. Among respondents with 1 or more iNO-treated patients per month, only 35%
      reported they know the oxygenation index level at which iNO should be initiated.
      Less than 20% of NNPs reported perceived benefits associated with early
      initiation of iNO for preventing progression to use of extracorporeal membrane
      oxygenation or reducing the length of hospital stay, and about one-third of
      respondents reported they believe early iNO use minimizes hyperoxia. IMPLICATIONS
      FOR PRACTICE: More education is needed for NNPs regarding the negative effects of
      oxidative stress in neonates. IMPLICATIONS FOR RESEARCH: Additional clinical
      trials investigating the most beneficial strategies for avoiding neonatal
      hyperoxia are warranted.

PMID- 29465449
TI  - A Comparison of Approaches for Mastery Learning Standard Setting.
AB  - PURPOSE: Defensible minimum passing standards (MPSs) must be used to evaluate
      learner performance outcomes in health professions education. In this study, the
      authors compared the results of traditional Angoff and Hofstee standard-setting
      exercises with the Mastery Angoff and Patient-Safety approaches for central
      venous catheter (CVC) insertion skills examinations. The authors also evaluated
      how these standards affected the historical performance of residents who
      participated in a simulation-based mastery learning (SBML) curriculum for CVC
      insertion skills. METHOD: In April and May 2015, 12 physicians with expertise in
      CVC insertion set MPSs for previously published internal jugular (IJ) and
      subclavian (SC) CVC insertion checklists using Angoff, Hofstee, Mastery Angoff,
      and Patient-Safety approaches. The resulting MPSs were compared using historical
      performance of internal medicine and emergency medicine residents who
      participated in CVC insertion SBML. RESULTS: The MPSs were set as follows:
      Angoff: IJ 91% checklist items correct, SC 90%. Hofstee: IJ 88%, SC 90%. Mastery
      Angoff: IJ 98%, SC 98%. Patient-Safety: IJ 98%, SC 98%. Based on the historical
      performance of 143 residents assessed on IJ and SC insertion, applying the 98%
      MPS would result in additional practice and retesting of 55/123 residents (45%)
      who had previously passed the IJ examination and 36/130 residents (28%) who had
      passed the SC examination using the Angoff and Hofstee MPSs. CONCLUSIONS: The
      Mastery Angoff and Patient-Safety standard-setting approaches resulted in higher
      CVC insertion SBML MPSs compared with traditional standard-setting methods.
      Further study should assess the impact of these more rigorous standards on
      patient outcomes.

PMID- 29465450
TI  - Gamification in Action: Theoretical and Practical Considerations for Medical
      Educators.
AB  - Gamification involves the application of game design elements to traditionally
      nongame contexts. It is increasingly being used as an adjunct to traditional
      teaching strategies in medical education to engage the millennial learner and
      enhance adult learning. The extant literature has focused on determining whether
      the implementation of gamification results in better learning outcomes, leading
      to a dearth of research examining its theoretical underpinnings within the
      medical education context. The authors define gamification, explore how
      gamification works within the medical education context using self-determination
      theory as an explanatory mechanism for enhanced engagement and motivation, and
      discuss common roadblocks and challenges to implementing gamification.Although
      previous gamification research has largely focused on determining whether
      implementation of gamification in medical education leads to better learning
      outcomes, the authors recommend that future research should explore how and under
      what conditions gamification is likely to be effective. Selective, purposeful
      gamification that aligns with learning goals has the potential to increase
      learner motivation and engagement and, ultimately, learning. In line with self
      determination theory, game design elements can be used to enhance learners'
      feelings of relatedness, autonomy, and competence to foster learners' intrinsic
      motivation. Poorly applied game design elements, however, may undermine these
      basic psychological needs by the overjustification effect or through negative
      effects of competition. Educators must, therefore, clearly understand the
      benefits and pitfalls of gamification in curricular design, take a thoughtful
      approach when integrating game design elements, and consider the types of
      learners and overarching learning objectives.

PMID- 29465451
TI  - How Mentor Identity Evolves: Findings From a 10-Year Follow-up Study of a
      National Professional Development Program.
AB  - PURPOSE: Despite academic medicine's endorsement of professional development and
      mentoring, little is known about what junior faculty learn about mentoring in
      implicit curricula of professional development programs, and how their mentor
      identity evolves in this context. The authors explored what faculty-participants
      in the Educational Scholars Program implicitly learned about mentoring and how
      the implicit curriculum affected mentor identity transformation. METHOD:
      Semistructured interviews with 19 of 36 former faculty-participants were
      conducted in 2016. Consistent with constructivist grounded theory, data
      collection and analysis overlapped. The authors created initial codes informed by
      Ibarra's model for identity transformation, iteratively revised codes based on
      incoming data patterns, and created visual representations of relationships
      amongst codes to gain a holistic, shared understanding of the data. RESULTS: In
      the implicit curriculum, faculty-participants learned the importance of having
      multiple mentors, the value of peer mentors, and the incremental process of
      becoming a mentor. The authors used Ibarra's model to understand how the implicit
      curriculum worked to transform mentor identity: Faculty-participants reported
      observing mentors, experimenting with different ways to mentor and to be a
      mentor, and evaluating themselves as mentors. CONCLUSIONS: The Educational
      Scholars Program's implicit curriculum facilitated faculty-participants taking on
      mentor identity via opportunities it afforded to watch mentors, experiment with
      mentoring, and evaluate self as mentor, key ingredients for identity
      construction. Leaders of professional development programs can develop faculty as
      mentors by capitalizing on what faculty-participants learn in the implicit
      curriculum and deliberately structuring postgraduation mentoring opportunities.

PMID- 29465452
TI  - Web-Enabled Mechanistic Case Diagramming: A Novel Tool for Assessing Students'
      Ability to Integrate Foundational and Clinical Sciences.
AB  - PROBLEM: As medical schools move from discipline-based courses to more integrated
      approaches, identifying assessment tools that parallel this change is an
      important goal. APPROACH: The authors describe the use of test item statistics to
      assess the reliability and validity of web-enabled mechanistic case diagrams
      (MCDs) as a potential tool to assess students' ability to integrate basic science
      and clinical information. Students review a narrative clinical case and construct
      an MCD using items provided by the case author. Students identify the
      relationships among underlying risk factors, etiology, pathogenesis and
      pathophysiology, and the patients' signs and symptoms. They receive one point for
      each correctly identified link. OUTCOMES: In 2014-2015 and 2015-2016, case
      diagrams were implemented in consecutive classes of 150 medical students. The
      alpha reliability coefficient for the overall score, constructed using each
      student's mean proportion correct across all cases, was 0.82. Discrimination
      indices for each of the case scores with the overall score ranged from 0.23 to
      0.51. In a G study using those students with complete data (n = 251) on all 16
      cases, 10% of the variance was true score variance, and systematic case variance
      was large. Using 16 cases generated a G coefficient (relative score reliability)
      equal to 0.72 and a Phi equal to 0.65. NEXT STEPS: The next phase of the project
      will involve deploying MCDs in higher-stakes settings to determine whether
      similar results can be achieved. Further analyses will determine whether these
      assessments correlate with other measures of higher-order thinking skills.

PMID- 29465453
TI  - Creation and Implementation of a Taxonomy for Educational Activities: A Common
      Vocabulary to Guide Curriculum Mapping.
AB  - PROBLEM: Undergraduate medical education (UME) has trended toward outcomes-based
      education, unveiling new issues for UME program organization and leadership.
      Using a common language for categorizing and linking all program components is
      essential. The Emory Curriculum Alignment Taxonomy (ECAT) was designed as a
      common vocabulary for curriculum mapping in the outcomes-based environment of the
      Emory University School of Medicine. APPROACH: The ECAT, developed in 2016, uses
      a set of 291 controlled identifiers, or "tags," to describe every educational
      activity's content, instruction, assessment, and outcomes, and thereby to align
      teaching inputs with student outcomes. Tags were drawn from external frameworks
      or developed by local stakeholders. A key feature is the arrangement of tags into
      eight categories, with the aim of balancing specificity and parsimony. Tags from
      multiple categories can be combined using Boolean operators to search for
      specific topics across the curriculum. OUTCOMES: In 2016-2017, all educational
      activities were tagged, including classroom events, workplace learning, mentored
      research, and student assessments. Tagging was done by two assistant deans and
      course/clerkship directors, which reinforced the importance of aligning
      instruction with assessment and aligning both of these with student outcomes.
      NEXT STEPS: Using the ECAT tags has linked instruction with achievement of
      student outcomes, has shown the compromises between specificity and parsimony
      were workable, and has facilitated comprehensive program management and
      evaluation. As the ECAT tags can be modified, other programs could adapt this
      approach to suit their context. Next steps will include aggregating data into a
      centralized repository to support reporting and research.

PMID- 29465454
TI  - The Impact of Surgeons on the Likelihood of Mastectomy in Breast Cancer.
AB  - OBJECTIVE: This study evaluates the impact of individual surgeons and
      institutions on the use of mastectomy or breast conserving surgery (BCS) among
      elderly women with breast cancer. SUMMARY OF BACKGROUND DATA: Current literature
      characterizes patient clinical and demographic factors that increase likelihood
      of mastectomy use. However, the impact of the individual provider or institution
      is not well understood, and could provide key insights to biases in the decision
      making process. METHODS: A retrospective cohort study of 29,358 women 65 years or
      older derived from the SEER-Medicare linked database with localized breast cancer
      diagnosed from 2000 to 2009. Multilevel, multivariable logistic models were
      employed, with odds ratios (ORs) used to describe the impact of demographic or
      clinical covariates, and the median OR (MOR) used to describe the relative impact
      of the surgeon and institution. RESULTS: Six thousand five hundred ninety-four
      women (22.4%) underwent mastectomy. Unadjusted rates of mastectomy ranged from 0%
      in the bottom quintile of surgeons to 58.0% in the top quintile. On multivariable
      analysis, the individual surgeon (MOR 1.97) had a greater impact on mastectomy
      than did the institution (MOR 1.71) or all other clinical and demographic
      variables except tumor size (OR 3.06) and nodal status (OR 2.95). Surgeons with
      more years in practice, or those with a lower case volume were more likely to
      perform mastectomy (P < 0.05). CONCLUSION: The individual surgeon influences the
      likelihood of mastectomy for the treatment of localized breast cancer. Further
      research should focus on physician-related biases that influence this decision to
      ensure patient autonomy.

PMID- 29465455
TI  - Commentary on Gomez et al.

PMID- 29465456
TI  - Transplantation Versus Resection for Hilar Cholangiocarcinoma: An Argument for
      Shifting Paradigms for Resectable Disease in Annals of Surgery 2018.

PMID- 29465457
TI  - Key Components of the Safe Surgical Ward: International Delphi Consensus Study to
      Identify Factors for Quality Assessment and Service Improvement.
AB  - OBJECTIVE: The aim of this study was to prioritize key factors contributing to
      safety on the surgical ward BACKGROUND:: There is a variation in the quality and
      safety of postoperative care between institutions. These variations may be
      attributed to a combination of process-related issues and structural factors. The
      aim of this study is to reach a consensus, by means of Delphi methodology, on the
      most influential of these components that may determine safety in this
      environment. METHODS: The Delphi questionnaire was delivered via an online
      questionnaire platform. The panel were blinded. An international panel of safety
      experts, both clinical and nonclinical, and safety advocates participated.
      Individuals were selected according to their expertise and extent of involvement
      in patient safety research, regulation, or patient advocacy. RESULTS: Experts in
      patient safety from the UK, Europe, North America, and Australia participated.
      The panel identified the response to a deteriorating patient and the care of
      outlier patients as error-prone processes. Prioritized structural factors
      included organizational and environmental considerations such as use of temporary
      staff, out-of-hours reduction in services, ward cleanliness, and features of
      layout. The latter includes dedicated areas for medication preparation and
      adequate space around the patient for care delivery. Potential quality markers
      for safe care that achieved the highest consensus include leadership, visibility
      between patients and nurses, and nursing team skill mix and staffing levels.
      CONCLUSION: International consensus was achieved for a number of factors across
      process-related and structural themes that may influence safety in the
      postoperative environment. These should be championed and prioritized for future
      improvements in patient safety at the ward-level.

PMID- 29465458
TI  - Prognostic Implications of Pathological Response to Neoadjuvant Chemoradiation in
      Pathologic Stage III Rectal Cancer.
AB  - OBJECTIVE: To evaluate the independent prognostic ability of the American Joint
      Committee on Cancer (AJCC) tumor regression scores within pathologic stage II and
      III rectal cancers. BACKGROUND: Response to neoadjuvant chemoradiation (nCRT) has
      been debated as a biologic surrogate for tumor biology and prognosis in rectal
      cancer. AJCC regression scores have been shown to correlate with prognosis.
      METHODS: Patient demographics, tumor characteristics, and AJCC scores (0 =
      complete response; 1 = isolated tumor cells remaining; 2 = residual cancer
      outgrown by fibrosis; 3 = extensive residual cancer) were assessed from 545
      rectal cancer patients treated by nCRT followed by surgery at a single
      institution. Patients were classified as responders (score 0-2) or nonresponders
      (score 3). Survival analyses were performed using Cox proportional hazards
      models. RESULTS: Of 545 cases, 123 and 182 were pathologic stage II and III,
      respectively. Median follow-up was 4.9 years. AJCC regression scores were not
      independently prognostic within stage II cancers. However, AJCC scores were
      strongly associated with prognosis within stage III cancers (nonresponse 5-year
      overall survival [OS] 27% vs 67%, P < 0.001). Stage III responders (N = 139,
      76.4%) had similar outcomes to stage II (5-year OS 67% vs 74%, P = 0.89).
      Conversely, stage III nonresponders (N = 43, 23.6%) approached stage IV outcomes
      (5-year OS 27% vs 18%, P = 0.09). On multivariable analysis, nonresponse (hazard
      ratio 3.2, 95% confidence interval 1.7-6.2), along with positive margin,
      abdominoperineal resection, and no adjuvant chemotherapy administration were
      independently associated with worse OS. CONCLUSIONS: AJCC response score after
      nCRT is a novel prognostic factor in pathologic stage III rectal cancer and may
      guide surveillance and adjuvant therapy decisions.

PMID- 29465459
TI  - Can We Do Better?: A Canadian Perspective on Firearm Injury Prevention.

PMID- 29465460
TI  - An Economic Evaluation of the National Surgical Quality Improvement Program
      (NSQIP) in Alberta, Canada.
AB  - OBJECTIVE: The aim of this study was to analyze the health care costs and savings
      associated with quality improvement (QI) interventions initiated and implemented
      utilizing NSQIP. BACKGROUND: Five acute care facilities of Alberta Health
      Services (AHS) adopted NSQIP in 2015 for a pilot project. METHODS: The cost
      savings of NSQIP were estimated from the start of NSQIP to the end of 2017 under
      an AHS perspective using this formula: Gross cost-savings = N * (p1 - p2) * unit
      cost, where N was the number of surgical patients after the intervention, p1 was
      the probability of event occurrence (within 30 days of surgery) before the
      intervention, p2 was the probability of event occurrence after the intervention,
      and unit cost is health care cost per event. To calculate the net cost-savings,
      we deducted the costs of NSQIP and its interventions from the gross cost-savings.
      RESULTS: The QI initiatives initiated by NSQIP to reduce surgical events had
      significant impacts clinically and economically. The gross cost-savings of NSQIP
      were estimated at $11.4 million. Subtracting the costs of NSQIP and its
      interventions ($2.6 million) from the gross cost-savings, the net cost-savings
      were $8.8 million. The return on investment ratio was 4.3, meaning that every
      $1.00 invested in NSQIP would bring $4.30 in returns. The sensitivity analysis
      showed the probability for NSQIP to be cost-saving was 95%. CONCLUSION: QI
      interventions initiated and implemented utilizing NSQIP appear to be effective
      and cost-saving for AHS. These cost-savings would be even larger if NSQIP was
      prolonged in the pilot sites and/or expanded to other sites across the province.

PMID- 29465461
TI  - Resident Autonomy in the Operating Room: How Faculty Assess Real-time
      Entrustability.
AB  - OBJECTIVE: This study aimed to identify the empirical processes and evidence that
      expert surgical teachers use to determine whether to take over certain steps or
      entrust the resident with autonomy to proceed during an operation. BACKGROUND:
      Assessing real-time entrustability is inherent in attending surgeons'
      determinations of residents' intraoperative autonomy in the operating room. To
      promote residents' autonomy, it is necessary to understand how attending surgeons
      evaluate residents' performance and support opportunities for independent
      practice based on the assessment of their entrustability. METHODS: We conducted
      qualitative semi-structured interviews with 43 expert surgical teachers from 21
      institutions across 4 regions of the United States, using purposeful and snowball
      sampling. Participants represented a range of program types, program size, and
      clinical expertise. We applied the Framework Method of content analysis to
      iteratively analyze interview transcripts and identify emergent themes. RESULTS:
      We identified a 3-phase process used by most expert surgical teachers in
      determining whether to take over intraoperatively or entrust the resident to
      proceed, including 1) monitoring performance and "red flags," 2) assessing
      entrustability, and 3) granting autonomy. Factors associated with individual
      surgeons (eg, level of comfort, experience, leadership role) and the context (eg,
      patient safety, case, and time) influenced expert surgical teachers'
      determinations of entrustability and residents' final autonomy. CONCLUSION:
      Expert surgical teachers' 3-phase process of decisions on take-over provides a
      potential framework that may help surgeons identify appropriate opportunities to
      develop residents' progressive autonomy by engaging the resident in the
      determination of entrustability before deciding to take over.

PMID- 29465462
TI  - Fatal Diesel Poisoning: A Case Report and Brief Review of Literature.
AB  - Hydrocarbons are volatile substances that are used in routine life activities for
      cooking or as automobile fuel. Diesel is one of the commonly used automobile
      fuels obtained from crude oil. Death due to poisoning by diesel is rarely
      reported. Most commonly affected is the respiratory system either after
      aspiration or ingestion. The most common presentation is chemical pneumonitis or
      aspiration pneumonitis from which patient usually recovers. Gas chromatography
      techniques help in the detection of volatile substances like diesel. Here, we
      report a rare case of fatal pediatric accidental diesel poisoning.

PMID- 29465463
TI  - Novel therapeutics for bronchopulmonary dysplasia.
AB  - PURPOSE OF REVIEW: This review provides a concise summary of recent literature
      pertaining to emerging therapies for bronchopulmonary dysplasia (BPD). To provide
      context for the presented therapies, a brief overview of recently proposed
      changes to the definition of BPD and the concept of expanded respiratory outcomes
      is included. RECENT FINDINGS: New or redefined respiratory outcomes are required
      to improve accuracy in evaluating new therapies and correlating results with long
      term clinical outcomes of importance. Dexamethasone is no longer the only steroid
      based therapy showing promise for impacting BPD. Early trials indicate
      hydrocortisone, inhaled budesonide, and a budesonide-surfactant combination may
      be of benefit to preterm infants. Additionally, simple approaches like increasing
      utilization of mother's own milk may deserve more emphasis. Of significant
      interest is the traction stem cell therapies are acquiring as one of the more
      anticipated treatments for BPD. A new preclinical meta-analysis demonstrates the
      benefits of mesenchymal stromal cell therapy in animal models while the results
      of early clinical trials remain eagerly awaited. SUMMARY: BPD continues to be the
      most frequently occurring significant morbidity for extremely preterm infants,
      yet highly effective therapies remain elusive. Promising new treatments are on
      the horizon, but only continued efforts to complete well-designed clinical trials
      will determine the true impact of these emerging therapies.

PMID- 29465464
TI  - Immunostimulating and cancer-reductive experimental therapy with the
      oxazaphosphorine cytostatic SUM-IAP.
AB  - SUM-IAP is an aldo-ifosfamide-perhydrothiazine derivative that, under
      physiological conditions, spontaneously hydrolyzes to SUM-aldo-ifosfamide. In SUM
      IAP, one 2-chloroethyl group of the alkylating function of aldo-ifosfamide
      perhydrothiazine is substituted by a mesyl-ethyl group. The compound was
      synthesized to investigate the influence of the alkylating function of aldo
      ifosfamide on the antitumor activity of oxazaphosphorine cytostatics. In
      chemotherapy experiments in CD2F1 mice with advanced subcutaneously growing P388
      mice leukemia cells, the primary tumor was reduced below the detection level with
      two highly dosed injections on days 7 and 8, but after 14 days, the primary tumor
      was measurable again. The primary tumor and detectable metastases killed the
      animals 29-30 days after SUM-IAP application. When, however, the animals were
      treated again with two highly dosed injections on day 14 and 15, a 4-5 times
      increase in the number of leukocytes was measured and all animals survived the
      observation period of 100 days. In the high, cancer-reductive dose range, SUM-IAP
      is not only a cytotoxic but also an immunostimulating oxazaphosphorine
      cytostatic.

PMID- 29465465
TI  - Pneumonia as a systemic illness.
AB  - PURPOSE OF REVIEW: The manuscript reviews the recent literature describing the
      occurrence, risk factors, recognition and treatment of sepsis, respiratory
      failure, and multiple organ dysfunction in patients with community-acquired
      pneumonia (CAP). RECENT FINDINGS: CAP may present with varying degrees of disease
      severity ranging from an almost asymptomatic infection to a fulminant systemic
      disease with both respiratory failure and multiple organ dysfunction. Severe
      sepsis occurs early in the course of the infection in more than 30% of cases. It
      may involve several organ systems and is associated with the severity and
      mortality of CAP. A number of factors exist, which may promote the transition of
      CAP from a local to a systemic disease, particularly immunosuppression and poorly
      controlled inflammatory responses, which promote extrapulmonary dissemination of
      the causative pathogens. Although CAP may be associated with complications
      involving most organ systems, much recent research has focused attention on
      cardiac complications, particularly those associated with pneumococcal
      infections. Biomarkers as a strategy for discriminating between invasive and
      noninvasive CAP have been comprehensively studied. A number of treatment
      strategies using antibiotics and various adjunctive therapies have been studied
      in severe CAP. SUMMARY: Recent research highlights the fact that CAP is
      frequently a systemic illness.

PMID- 29465466
TI  - The prevalence of unexplained falls and syncope in older adults presenting to an
      Irish urban emergency department.
AB  - AIM: There is growing evidence of an overlap between unexplained falls and
      syncope in older adults. Our aim was to examine the prevalence and associated
      resource utilization of these conditions in an urban emergency department (ED).
      PATIENTS AND METHODS: A single-centre, prospective, observational study was
      carried out over a 6-month period. Consecutive patients older than 50 years who
      presented to the ED because of a fall, collapse or syncope were included.
      Univariate analysis of demographic data is presented as percentages, mean (SD),
      95% confidence intervals (CIs) and medians (interquartile range). Logistic
      regression modelling was used to examine the association between falls and
      resource utilization. RESULTS: A total of 561 patients fulfilled the inclusion
      criteria during the study period. Unexplained fallers accounted for 14.3% (n=80;
      95% CI: 13.3-15.3) and syncope for 12.7% (n=71; 95% CI: 11.7-13.6) of all fall
      presentations. Overall, 50% (n=282; 95% CI: 48.20-52.34) of patients required
      admission to hospital. Patients with syncope [odds ratio (OR)=2.48, 95% CI: 1.45
      4.23], and unexplained falls (OR=2.36, 95% CI: 1.37-4.08) were more likely to
      require admission than those with an explained falls. Unexplained fallers were
      nearly five times more likely to suffer recurrent falls (OR=4.97, 95% CI: 2.89
      8.56). CONCLUSION: One in four older fallers presenting to ED have symptoms
      suggestive of syncope or an unexplained fall. There are significant biological
      consequences of recurrent falls including greater rates of cognitive decline,
      gait and mobility disturbances, depression and frailty. Recognition that syncope
      can present as an unexplained fall in older adults is important to ensure that
      appropriate early modifiable interventions are initiated.

PMID- 29465468
TI  - Getting personal: towards individualized management of rheumatoid arthritis.

PMID- 29465467
TI  - Outcome and predictors of remission in bipolar-I patients experiencing manic
      episode and treated with oral antipsychotics and/or mood stabilizers: a
      prospective observational study in Italy.
AB  - This observational study aimed to identify internal (clinical-demographic,
      temperamental characteristics) and external (childhood trauma, psychosocial
      characteristics) factors potentially predicting remission at 12 weeks in bipolar
      I patients experiencing manic episode and requiring to start or switch treatment
      with oral antipsychotics and/or mood stabilizers. The following scales were
      administered: the Young Mania Rating Scale (YMRS), the Montgomery-Asberg
      Depression Rating Scale (MADRS), the Functioning Assessment Short Test (FAST),
      and the Clinical Global Impression for Bipolar Disorders (CGI-BP). A logistic
      regression analysis was carried out to test the effect of the explored factors on
      remission rate (YMRS score <=12), functionality, and clinical outcomes at week
      12. Overall, 243 patients were enrolled and 197 (81.1%) completed the follow-up.
      Remission at week 12 was achieved in 200 (82.3%) patients. Marked improvements
      from baseline were observed in MADRS, FAST, CGI-BP mania, and bipolar illness
      scores. None of the factors was associated with remission, or showed strong
      correlations with the improvements in clinical health state. In our sample, after
      12 weeks of initiation or change of oral therapy for mania in bipolar-I patients,
      treatment was associated with rapid improvements in symptoms and functioning in
      most patients. Factors predictive of remission and clinical improvements in manic
      symptoms were not identified.

PMID- 29465469
TI  - A critical appraisal of gabapentinoids for pain in cancer patients.
AB  - PURPOSE OF REVIEW: Gabapentinoids are frequently used in the management of cancer
      pain. In recent Cochrane systematic reviews, although there was an abundance of
      evidence relating to non-cancer pain, only a few studies related to cancer pain.
      This review summarizes recent randomised controlled trials (RCTs) evaluating the
      use of gabapentinoids for tumour-related (as monotherapy or part of combination
      therapy) and treatment-related pain. RECENT FINDINGS: For tumour-related pain,
      ten out of thirteen studies showed statistically significant benefits in favour
      of gabapentinoids. When used, as part of monotherapy or combination therapy,
      benefits were observed in five out of six studies evaluating gabapentin, and in
      six out of eight studies evaluating pregabalin. For treatment-related pain, none
      of the four studies (two gabapentin, two pregabalin) showed statistically
      significant benefits in favour of gabapentinoids. Unfortunately, many of the
      studies included were limited by small sample size, lack of blinding, and
      inadequate follow-up. SUMMARY: More and better quality studies are required,
      although it may be challenging to accomplish in this patient population.
      Gabapentinoids may offer benefits to cancer patients with pain, but careful
      titration and monitoring of adverse effects is necessary.

PMID- 29465470
TI  - Opioid addiction, diversion, and abuse in chronic and cancer pain.
AB  - PURPOSE OF REVIEW: The primary cause of overdose death in the United States is
      related to pharmaceutical opioids. A few particular populations that struggle
      with adverse outcomes related to opioid abuse are those in palliative care, those
      with chronic pain, and those receiving pain treatments secondary to cancer or
      chemotherapy. RECENT FINDINGS: There have been massive efforts to decrease the
      use of opioid abuse in patient care in a gestalt manner, but palliative care
      provides unique challenges in applying these reduction tactics used by other
      specialties. SUMMARY: We explore behavioral interventions, provider education,
      alternative pain management techniques, postmarketing surveillance, and abuse
      deterrent formulas as emerging methods to counteract opioid abuse in these
      populations.

PMID- 29465471
TI  - Perioperative venous thromboembolism in urologic oncology procedures, risk
      factors, and prevention.
AB  - PURPOSE OF REVIEW: Venous thromboembolism (VTE) is a common complication during
      the perioperative period for major urologic oncology operations. The present
      review focuses on the risk factors, the mechanisms of hypercoagulability in this
      patient population, and the timing and prevention of VTE. RECENT FINDINGS:
      Although the vast majority of patients undergoing major urologic oncology
      operations do not develop VTEs, when they do develop they can be fatal. The risk
      factors for VTEs are important to identify in this patient population. The timing
      of VTE events are also essential to understanding their prevention. Prevention
      focused around the perioperative period is the best way to reduce fatal
      complications secondary to a VTE event. SUMMARY: VTEs are common and can
      potentially be fatal. Prevention in high-risk patients during the most vulnerable
      perioperative time period should be the focus of clinical efforts to reduce VTE
      complications and the associated morbidity and mortality.

PMID- 29465472
TI  - A new prognostic score can predict survival after hepatocellular carcinoma
      treatment in a cohort of 1302 Egyptian hepatocellular carcinoma patients.
AB  - INTRODUCTION: Survival of hepatocellular carcinoma (HCC) differs between regions
      and countries according to the different underlying factors and the degree of
      standard of care that enables early diagnosis and management. Our aim was to
      identify the most potent predictive factors of survival in Egyptian HCC patients
      receiving curative or palliative treatments. PATIENTS AND METHODS: This
      retrospective study included 1302 HCC patients attending the HCC
      multidisciplinary clinic, Cairo University, between February 2009 and December
      2016. Clinical, laboratory, tumor characteristics, and treatment data were
      collected. Prognostic scores for each of the treatment categories, curative or
      palliative, were developed using routine laboratory tests. RESULTS: Patients were
      predominantly men, mean age 57.79+/-7.56 years. All cases developed HCC in
      addition to cirrhosis, mainly hepatitis C virus-related (88.2%). Most of the
      patients were Child-Pugh A (56.8%) or B (34.4%) and had single lesions.
      Transarterial chemoembolization was the most common line of treatment (42.08%).
      The overall median survival was 18.3 months from the date of diagnosis. Cigarette
      smoking, Child-Pugh score, performance status, number and size of the focal
      lesion, alpha-fetoprotein, and application of a specific treatment, particularly
      curative treatment, were the significant independent prognostic factors for
      survival. We found no impact of diabetes mellitus or hypertension on survival.
      Multidisciplinary HCC clinic predictive scores of survival after palliative and
      curative treatments were developed including independent prognostic factors, age,
      and portal vein status. CONCLUSION: A new Egyptian prognostic score of tumor and
      patients factors can predict the survival of patients with HCC after palliative
      and curative treatments.

PMID- 29465473
TI  - Characteristics of patients with hepatitis C virus-related chronic liver diseases
      just before the era of oral direct-acting antiviral therapy in Italy.
AB  - BACKGROUND: In 2017, oral direct-acting antiviral (DAA) therapy for chronic
      hepatitis C virus (HCV) infection became available free of charge for all HCV-RNA
      positive patients, irrespective of their fibrosis stage. AIM: The aim of this
      study was to evaluate the characteristics of HCV-related chronic liver disease
      (CLD) in Italy just before the introduction of DAA therapy. PATIENTS AND METHODS:
      Patients with CLD were enrolled in two national surveys conducted in 2001 and in
      2014. The two surveys prospectively enrolled patients aged older than 18 years
      referring to Italian liver units throughout the country using a similar clinical
      approach and analytical methods. RESULTS: Out of the 12 564 patients enrolled,
      8447 (67.3%) were anti-HCV-positive, with a decreasing trend from 69.0% in 2001
      to 60.4% in 2014. During this period, an increasing trend over time was observed
      in the mean age of patients (55.6 vs. 59.1 years; P<0.01), in the proportion of
      patients with liver cirrhosis (19.4 vs. 28.2%; P<0.01), and in the circulation of
      genotype 4 (0 vs. 6.1%). The multiple logistic analysis showed that age older
      than 60 years, birth in southern Italy, and multiple etiology (HCV+hepatitis B
      virus or HCV+alcohol) are independent predictors of a likelihood of liver
      cirrhosis, whereas a higher level of education plays a protective role (odds
      ratio: 0.65; 95% confidence interval=0.57-0.76). CONCLUSION: Currently, in Italy,
      chronic HCV infection plays a decreasing role in CLD, showing a shift toward
      older age groups and a more severe disease stage. These data, relating to just
      before the era of DAA therapy for this infection, represent up-to-date reference
      data for evaluating the effectiveness of DAAs in the future.

PMID- 29465474
TI  - Smartphone technology: a reliable and valid measure of knee movement in knee
      replacement.
AB  - Knee range of motion (ROM) following a knee arthroplasty is an important clinical
      outcome that directly relates to the patient's physical function. Smartphone
      technology has led to the creation of applications that can measure ROM. The aim
      was to determine the concurrent reliability and validity of the photo-based
      application 'Dr Goniometer' (DrG) compared with a universal goniometer performed
      by a clinician. A smartphone camera was used to take photographs of the knee in
      full flexion and full extension, and the images were sent by participants to a
      study phone. Participants then rated the ease of participation. To assess
      validity, the patient's knee was measured by a clinician using a goniometer. To
      examine reliability, four clinicians assessed each image using DrG on four
      separate occasions spaced 1 week apart. A total of 60 images of knee ROM for 30
      unicondylar or total knee arthroplasty were assessed. The goniometer and DrG
      showed strong correlations for flexion (r=0.94) and extension (r=0.90). DrG
      showed good intrarater reliability and excellent inter-rater reliability for
      flexion (intraclass correlation coefficient=0.990 and 0.990) and good reliability
      for extension (intraclass correlation coefficient=0.897 and 0.899). All
      participants found the process easy. DrG was proven to be a valid and reliable
      tool in measuring knee ROM following arthroplasty. Smartphone technology, in
      conjunction with patient-reported outcomes, offers an accurate and practical way
      to remotely monitor patients. Benefit may be found in differentiating those who
      need face-to-face clinical consult to those who do not.

PMID- 29465476
TI  - Idiopathic pulmonary fibrosis: A guide for nurse practitioners.
AB  - Idiopathic pulmonary fibrosis (IPF) is a rare disease characterized by decline in
      lung function, dyspnea, and cough. The clinical course of IPF is variable and
      unpredictable. Early referral to specialists is key to ensure timely and accurate
      diagnosis. Two antifibrotic drugs (nintedanib and pirfenidone) have been approved
      for the treatment of IPF.

PMID- 29465475
TI  - Physical Activity and Bone Accretion: Isotemporal Modeling and Genetic
      Interactions.
AB  - PURPOSE: This study aimed to determine if replacing time spent in high- and low
      impact physical activity (PA) predicts changes in pediatric bone mineral density
      (BMD) and content (BMC). METHODS: We analyzed data from the longitudinal Bone
      Mineral Density in Childhood Study (N = 2337 with up to seven visits). The
      participants were age 5-19 yr at baseline, 51.2% were female, and 80.6% were
      nonblack. Spine, total hip, and femoral neck areal BMD and total body less head
      (TBLH) BMC Z-scores were calculated. Hours per day spent in high- and low-impact
      PA were self-reported. Standard covariate-adjusted (partition model) and time
      allocation-sensitive isotemporal substitution modeling frameworks were applied to
      linear mixed models. Statistical interactions with sex, self-reported ancestry,
      age, and bone fragility genetic scores (percentage of areal BMD-lowering alleles
      carried) were tested. RESULTS: In standard models, high-impact PA was positively
      associated with bone Z-score at all four skeletal sites (e.g., TBLH-BMC Z-score:
      beta = 0.05, P = 2.0 * 10), whereas low-impact PA was not associated with any of
      the bone Z-scores. In isotemporal substitution models, replacing 1 h.d of low-
      for high-impact PA was associated with higher bone Z-scores (e.g., TBLH-BMC Z
      score: beta = 0.06, P = 2.9 * 10). Conversely, replacing 1 h.d of high- for low
      impact PA was associated with lower bone Z-scores (e.g., TBLH-BMC Z-score: beta =
      -0.06, P = 2.9 * 10). The substitution associations were similar for each sex and
      ancestry group, and for those with higher and lower genetic scores for bone
      fragility (P-interactions > 0.05), but increased in strength among the older
      adolescents (P-age interactions < 0.05). CONCLUSIONS: Time-sensitive models
      suggest that replacing low-impact PA for high-impact PA would be beneficial for
      the growing skeleton in the majority of children.

PMID- 29465477
TI  - Personal Bias in Scientific Review: We Can Do Better.

PMID- 29465480
TI  - Impact of Fever and Antipyretic Use on Influenza Vaccine Immune Reponses in
      Children.
AB  - BACKGROUND: Comparing postvaccination fever rates in pediatric influenza vaccine
      clinical trials is difficult due to variability in how fever is reported. The
      impact of vaccine-related fever and antipyretic use on trivalent influenza
      vaccine immunogenicity in children is also unclear. METHODS: In this pilot study,
      we used individual-level data provided by GlaxoSmithKline from 3 pediatric
      clinical trials of GlaxoSmithKline versus comparator trivalent influenza vaccine.
      We explored a primary study (NCT00764790), the largest trial involving young
      children (6-35 months, n = 3317), and further explored key findings in the 2
      other trials (3-17 years, NCT00980005; 6 months to 17 years, NCT00383123). We
      analyzed postvaccination fever and antipyretic use, and their association with
      immunogenicity through use of multivariable regression. RESULTS: Postvaccination
      fever data were reanalyzed from the primary study using the Brighton
      Collaboration standardized definition (vaccine-related fever >=38 degrees C,
      measured by any route, reported after each dose). Rates were substantially lower
      after first (2.7%-3.4%) and second doses (3.3%-4.1%), than those published (6.2%
      6.6%; combined dose data, any causality). A pooled immunogenicity analysis
      combining the 3 studies (n = 5902) revealed children with postvaccination fever
      had significantly higher adjusted geometric mean titers than those without fever
      (ratio, 1.21-1.39; P <= 0.01). Conversely those with antipyretic use had
      significantly lower adjusted geometric mean titers (ratio, 0.80-0.87; P <
      0.0006), dependent on virus strain. CONCLUSIONS: Varying analyses and reporting
      methods can result in substantially different reported fever rates in studies.
      Standardized reporting of fever is needed to facilitate comparison between
      studies. Fever and antipyretic use may have important associations with influenza
      vaccine immunogenicity in children and need further prospective investigation.

PMID- 29465478
TI  - Glutamatergic Modulators in Depression.
AB  - LEARNING OBJECTIVE: After participating in this activity, learners should be
      better able to evaluate the evidence supporting the antidepressant effects of
      glutamatergic modulators.Both preclinical and clinical studies have implicated
      glutamatergic system dysfunction in the pathophysiology of mood disorders such as
      bipolar depression and major depressive disorder. In particular, rapid reductions
      in depressive symptoms have been noted in response to subanesthetic doses of the
      glutamatergic modulator ketamine in subjects with major depressive disorder or
      bipolar depression. These results have prompted the repurposing or development of
      other glutamatergic modulators, both as monotherapy or adjunctive to other
      therapies. Here, we highlight the evidence supporting the antidepressant effects
      of various glutamatergic modulators, including (1) broad glutamatergic modulators
      (ketamine, esketamine, dextromethorphan, dextromethorphan-quinidine [Nuedexta],
      AVP-786, nitrous oxide [N2O], AZD6765), (2) subunit (NR2B)-specific N-methyl-D
      aspartate (NMDA) receptor antagonists (CP-101,606/traxoprodil, MK-0657 [CERC
      301]), (3) glycine-site partial agonists (D-cycloserine, GLYX-13, sarcosine, AV
      101), and (4) metabotropic glutamate receptor modulators (AZD2066,
      RO4917523/basimglurant, JNJ40411813/ADX71149, R04995819 [RG1578]).

PMID- 29465481
TI  - Murine Typhus in South Texas Children: An 18-year Review.
AB  - BACKGROUND: Murine typhus is a zoonotic infection caused by Rickettsia typhi that
      remains endemic in South Texas. In 2003, only 9 Texas counties reported murine
      typhus compared with 41 counties in 2013. METHODS: A retrospective study of
      children discharged with a confirmed diagnosis of murine typhus from Driscoll
      Children's Hospital between January 1998 and September 2016. RESULTS: Two hundred
      thirteen children (113 female) 3 months through 19 years of age (mean, 11.2 +/-
      4.5 years) were identified. Cases occurred throughout the year. Children were
      admitted after a mean of 7.7 +/- 5.3 days of fever. The most common symptoms were
      fever (100%), poor appetite (71.9%), malaise/fatigue (69.0%) and headache
      (67.6%). The most common laboratory abnormalities were elevated C-reactive
      protein, hypoalbuminemia, elevated erythrocyte sedimentation rate, elevated
      transaminases and elevated band count with normal total white blood cell count.
      Children defervesced in a mean of 31.87 +/- 21.36 hours after initiation of
      doxycycline. Hospitalization lasted for a mean of 2.7 +/- 1.8 days when children
      were administered doxycycline within 24 hours of admission compared with, 4.1 +/-
      1.8 days, P <= 0.0001 when started later. Eleven patients (5.1%) were admitted to
      the pediatric intensive care unit and were older, P = 0.0009. No children died.
      CONCLUSIONS: Murine typhus is endemic in South Texas. Children who were treated
      earlier with doxycycline had a shorter hospitalization than were those who began
      therapy later. Recognition of murine typhus is important to prevent delay in
      treatment and development of complications.

PMID- 29465479
TI  - Ketamine-Associated Brain Changes: A Review of the Neuroimaging Literature.
AB  - Major depressive disorder (MDD) is one of the most prevalent conditions in
      psychiatry. Patients who do not respond to traditional monoaminergic
      antidepressant treatments have an especially difficult-to-treat type of MDD
      termed treatment-resistant depression. Subanesthetic doses of ketamine-a
      glutamatergic modulator-have shown great promise for rapidly treating patients
      with the most severe forms of depression. As such, ketamine represents a
      promising probe for understanding the pathophysiology of depression and treatment
      response. Through neuroimaging, ketamine's mechanism may be elucidated in humans.
      Here, we review 47 articles of ketamine's effects as revealed by neuroimaging
      studies. Some important brain areas emerge, especially the subgenual anterior
      cingulate cortex. Furthermore, ketamine may decrease the ability to self-monitor,
      may increase emotional blunting, and may increase activity in reward processing.
      Further studies are needed, however, to elucidate ketamine's mechanism of
      antidepressant action.

PMID- 29465482
TI  - Soft Tissue Metrics in Thyroid Eye Disease: An International Thyroid Eye Disease
      Society Reliability Study.
AB  - PURPOSE: To determine the reliability of 3 scales for assessing soft tissue
      inflammatory and congestive signs associated with thyroid eye disease. METHODS:
      This was a multicentered prospective observational study, recruiting 55 adults
      with thyroid eye disease from 9 international centers. Six thyroid eye disease
      soft tissue features were measured; each sign graded using 3 scales
      (presence/absence [0-1], 3-point scale [0-2], and percentage [0-100]). Each eye
      was graded twice by 2 independent raters. Accuracy (fraction of agreement) was
      calculated between the 2 trials for each rater (intrarater reliability) and
      between raters for all trials (interrater reliability) to determine the most
      sensitive scale for each feature that maintained a threshold of agreement greater
      than 0.70. Trial, intrarater reliability, and interrater reliability were
      determined by accuracy measurement of agreement for each inflammatory/congestive
      feature. RESULTS: Fifty-five patients had 218 assessments for 6 thyroid eye
      disease metrics. The intrarater reliability for each feature was consistently
      better than the interrater reliabilities. Using an agreement of 0.70 or better,
      for the interrater tests, conjunctival and eyelid edema could be reliably
      measured using the 0-1 or 0-2 scale while conjunctival and eyelid redness could
      only be reliably measured with the binary 0-1 scale. Caruncular edema and
      superior conjunctival redness could not be measured reliably between 2 raters
      with any scale. The percentage scale had poor agreement unless slippage intervals
      of >20% were allowed on either side of the measurements. CONCLUSIONS: Of the
      specific periocular soft tissue inflammatory features measured between raters in
      the Clinical Activity Score and Vision, Inflammation, Strabismus, Appearance
      scales, edema of the eyelids and conjunctiva could reliably be measured by both 0
      1 and 0-2 scales, erythema of the eyelid and bulbar conjunctiva could reliably be
      measured only by the 0-1 scale, and the other parameters of superior bulbar
      erythema and caruncular edema were not reliably measured by any scale.

PMID- 29465483
TI  - Case Series: Noninflammatory Thyroid Eye Disease.
AB  - PURPOSE: Patients presenting with thyroid eye disease (TED) usually follow a well
      defined self-remitting course characterized by an active inflammatory phase
      followed by an inactive fibrotic phase. We present 3 cases where patients
      presented primarily with signs of progressive fibrosis and no signs of prior
      active inflammation. METHODS: We reviewed the clinical notes and investigations
      of 3 patients who presented to our center between January 2015 and August 2017.
      RESULTS: All patients included in the study presented primarily with severe,
      progressive fibrosis without evidence of a previous active inflammatory
      condition. Although there were no signs of inflammation, each case was
      progressive, with 2 of the cases developing dysthyroid optic neuropathy that was
      relatively recalcitrant. We found that these patients were older than the general
      population of TED patients and that their disease course represents a departure
      from the common narrative. CONCLUSIONS: This subgroup of TED patients do not
      conform to the typical inflammatory natural history of TED. We propose that the
      heterogeneity of the orbital fibroblast pool and their function may be different
      in this subgroup. Further work will be required to reveal the pathophysiology of
      this atypical TED process, potentially revealing links between aging and the
      inflammatory mediators in TED.

PMID- 29465484
TI  - Expansion Vibration Lipofilling: A New Technique in Large-Volume Fat
      Transplantation.
AB  - BACKGROUND: Despite rapid growth, gluteal fat transplantation is an operation in
      search of science and a teachable technique. Long operating times, tedious
      syringe transfers, inability to shape the recipient site, and the risk of fat
      embolism all headline as impediments to clinical adoption of the procedure.
      Expansion vibration lipofilling is a syringe-free surgical strategy that is a
      logical extension of Separation, Aspiration, and Fat Equalization (SAFELipo). In
      expansion vibration lipofilling, there is simultaneous disruption of recipient
      site connective tissue, internal expansion using exploded-tip cannulas, and
      backfilling of these spaces with roller pump-propelled fat. METHODS: Two thousand
      four hundred nineteen consecutive cases of expansion vibration lipofilling fat
      transplantation to the buttocks were reviewed. Average follow-up was 12 months.
      The technique of expansion vibration lipofilling is dependent on the use of
      larger caliber cannulas attached to a roller pump and to an oscillatory power
      assisted liposuction device, which is less labor-intensive, potentially allowing
      for better knowledge of cannula-tip location at all times during the procedure.
      RESULTS: Operating times averaged 1 hour 40 minutes. The average volume of fat
      inserted was 1003 cc. Complications included donor-site seroma, infection, and
      one pulmonary embolism treated with anticoagulation. There were no cases of fat
      embolism or death. CONCLUSIONS: Expansion vibration lipofilling is a new method
      for large-volume fat transplantation. Avoidance of fatal fat emboli demands a
      surgeon's complete knowledge of cannula tip location at all times during the
      procedure. Syringe-free, larger caliber, and less flexible cannulas, combined
      with techniques requiring less operator upper extremity effort resulting in less
      fatigue, may contribute to avoidance of this dreadful complication. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 29465486
TI  - Hypercholesterolemia Is Associated with the Subjective Evaluation of
      Postoperative Outcomes in Patients with Idiopathic Carpal Tunnel Syndrome Who
      Undergo Surgery: A Multivariate Analysis.
AB  - BACKGROUND: Carpal tunnel syndrome is a compression neuropathy of the median
      nerve at the wrist; its symptoms include neuropathic pain and sensory and motor
      disturbance distributed by the median nerve. Carpal tunnel syndrome and
      hypercholesterolemia have similar backgrounds, but the effect of these
      similarities on postoperative outcomes has not been reported. Using multivariate
      analysis, the authors analyzed the relationship between prognostic factors,
      including the presence of hypercholesterolemia, and subjective postoperative
      outcomes of patients with idiopathic carpal tunnel syndrome. METHODS: Of 168
      hands with carpal tunnel syndrome that were treated surgically, 141 that were
      followed up and assessed 1 year postoperatively or thereafter were included. The
      mean postoperative follow-up period was 40.8 months. Surgery was performed
      through a small palmar skin incision under local anesthesia. The outcomes were
      postoperative symptoms, including pain and numbness, and overall Kelly
      assessment. RESULTS: Preoperative numbness and pain resolved and alleviated in 94
      of 141 hands and was diminished in 59 of 64 hands. Univariate analysis showed
      that postoperative numbness and Kelly assessment were significantly associated
      with hypercholesterolemia. Multivariate analysis showed that postoperative
      numbness was significantly associated with smoking and hypercholesterolemia, and
      Kelly assessment was significantly associated with smoking (adjusted OR, 3.3; 95
      percent CI, 1.1 to 10; p = 0.04) and hypercholesterolemia (adjusted OR, 2.9; 95
      percent CI, 1.4 to 6.3; p = 0.01). CONCLUSION: Hypercholesterolemia, usually a
      systemic condition in sites other than the hand, is associated with the
      subjective evaluation of postoperative symptoms in patients with idiopathic
      carpal tunnel syndrome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 29465485
TI  - Enhanced Recovery Pathway in Microvascular Autologous Tissue-Based Breast
      Reconstruction: Should It Become the Standard of Care?
AB  - BACKGROUND: Enhanced recovery pathway programs have demonstrated improved
      perioperative care and shorter length of hospital stay in several surgical
      disciplines. The purpose of this study was to compare outcomes of patients
      undergoing autologous tissue-based breast reconstruction before and after the
      implementation of an enhanced recovery pathway program. METHODS: The authors
      retrospectively reviewed consecutive patients who underwent autologous tissue
      based breast reconstruction performed by two surgeons before and after the
      implementation of the enhanced recovery pathway at a university center over a 3
      year period. Patient demographics, perioperative data, and 45-day postoperative
      outcomes were compared between the traditional standard of care (pre-enhanced
      recovery pathway) and enhanced recovery pathway patients. Multivariate logistic
      regression was performed to identify risk factors for length of hospital stay.
      Cost analysis was performed. RESULTS: Between April of 2014 and January of 2017,
      100 consecutive women were identified, with 50 women in each group. Both groups
      had similar demographics, comorbidities, and reconstruction types.
      Postoperatively, the enhanced recovery pathway cohort used significantly less
      opiate and more acetaminophen compared with the traditional standard of care
      cohort. Median length of stay was shorter in the enhanced recovery pathway
      cohort, which resulted in an extrapolated $279,258 savings from freeing up
      inpatient beds and increase in overall contribution margins of $189,342.
      Participation in an enhanced recovery pathway program and lower total morphine
      equivalent use were independent predictors for decreased length of hospital stay.
      Overall 45-day major complication rates, partial flap loss rates, emergency room
      visits, hospital readmissions, and unplanned reoperations were similar between
      the two groups. CONCLUSION: Enhanced recovery pathway program implementation
      should be considered as the standard approach for perioperative care in
      autologous tissue-based breast reconstruction because it does not affect
      morbidity and is associated with accelerated recovery with reduced postoperative
      opiate use and decreased length of hospital stay, leading to downstream health
      care cost savings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29465487
TI  - Incidental Detection of Type B2 Thymoma on 68Ga-Labeled Prostate-Specific
      Membrane Antigen PET/CT Imaging.
AB  - Ga-labeled prostate-specific membrane antigen is a novel radiotracer for imaging
      of prostate cancer. We report a hormonally treated patient with prostate
      carcinoma, presenting with lower urinary tract symptoms and rising prostate
      specific antigen levels, who underwent Ga-labeled prostate-specific membrane
      antigen PET/CT for suspected recurrence. No tracer avid lesion was noted in the
      prostate gland and locoregional area. However, intense tracer avid
      heterogeneously enhancing soft tissue lesion with cystic areas and coarse
      calcifications was seen in the anterior mediastinum. PET/CT-guided biopsy from
      the mediastenal lesion revealed type B2 thymoma.

PMID- 29465488
TI  - FDG PET and MRI Findings in a Case of Bing-Neel Syndrome.
AB  - A 64-year-old man was admitted for expressive aphasia with lack of words. He had
      been diagnosed with Waldenstrom 4 years before. At that time, he received 6
      cycles of single-agent fludarabine, and remission was obtained. Because of acute
      expressive aphasia, he underwent brain MRI, which showed frontoparietal and
      insular subcortical gadolinium enhancement; Bing-Neel syndrome was suspected.
      Fronto-temporo-insular hypometabolism and left parietal hypometabolism were
      highlighted on FDG PET/CT. Structural and functional brain imaging revealed
      impairment of brain areas due to white matter changes and reinforced the
      diagnosis.

PMID- 29465489
TI  - Small Lymph Node Metastasis Detected by 68Ga-Prostate-Specific Membrane Antigen
      But Not 18F-Fluciclovine PET/CT in Low-Prostate-Specific Antigen Biochemical
      Recurrence of Prostate Cancer.
AB  - A 58-year-old man with Gleason 4+3 prostate cancer was initially treated by
      radical prostatectomy followed by salvage radiotherapy to the prostate bed for
      postoperative biochemical failure. One year later, F-fluorocholine PET/CT
      detected a pelvic lymph node recurrence, which was treated with radiation therapy
      and 6 months of androgen deprivation. PSA started to rise again 18 months later,
      but F-fluciclovine PET/CT failed to demonstrate the site of recurrence at a PSA
      of 0.63 ng/mL. However, Ga-PSMA PET/CT revealed a single positive 4-mm perirectal
      lymph node (PSA 0.80 ng/mL at time of scan), in retrospect anatomically apparent
      but negative on F-fluciclovine PET/CT.

PMID- 29465490
TI  - 99mTc-MDP SPECT-CT and Ultrasound in the Diagnosis and Staging of Thyroid
      Metastasis From Osteosarcoma.
AB  - The classification of thyroid nodules in children is often difficult, especially
      in pretreated patients with metastatic disease. In osteosarcoma patients, Tc-MDP
      SPECT/CT is used for primary and follow-up staging. Bone and soft tissue
      metastases can be revealed because of Tc-MDP imaging of osteoid-producing
      metastases. We present Tc-MDP SPECT-CT, CT, and ultrasound images of a highly
      suspicious calcified thyroid lesion in a 17-year-old boy with osteosarcoma. High
      uptake in Tc-MDP SPECT-CT provides diagnosis of thyroid metastasis of
      osteosarcoma, which was proven by histopathology.

PMID- 29465491
TI  - Is There Any Potential of FDG PET/CT in Monitoring Disease Activity in Familial
      Hemophagocytic Lymphohistiocytosis?
AB  - FDG PET/CT was performed in a 30-year-old woman to detect the source of fever of
      unknown origin. The images showed widespread abnormal activity, consistent with
      lymphoma. However, lymph node biopsy revealed only inflammation, and a diagnosis
      of familial hemophagocytic lymphohistiocytosis was eventually made after familial
      hemophagocytic lymphohistiocytosis-specific gene was detected. After proper
      therapy, a follow-up FDG PET/CT examination 2 months later showed resolution of
      most of the previously seen lesions.

PMID- 29465492
TI  - Seizure-Induced Increased 18F-DOPA Uptake in a Child With Diffuse Astrocytoma and
      Transient Brain MRI Abnormalities Related to Status Epilepticus.
AB  - We report the finding of increased F-DOPA uptake in the brain parenchyma
      surrounding a temporoparietal low-grade diffuse astrocytoma and corresponding to
      transient seizure-induced MRI abnormalities. There was concomitant markedly
      increased tumoral uptake. This F-DOPA PET phenomenon may represent increased
      amino acid transport induced by seizures. In the setting of brain tumor imaging,
      increased F-DOPA uptake of low-grade epileptogenic tumors and adjacent brain
      parenchyma should be carefully interpreted in light of clinical and
      electroencephalographic findings related to seizure activity.

PMID- 29465493
TI  - Unusual Case of Diffuse Penile Metastasis of Prostate Cancer on 68Ga PSMA PET/CT
      Imaging and 177Lu PSMA Posttherapy Scintigraphy.
AB  - An 85-year-old man with prostate cancer for metastatic workup underwent Gallium
      Prostate-Specific Membrane Antigen (Ga-PSMA) PET/CT (Ga-PSMA PET/CT), which
      revealed unusual tracer uptake in the shaft and glans of penis as well as
      multiple systemic metastases in liver, skeletal, and lymph nodes. The penile
      lesion was proved to be metastatic adenocarcinoma from prostate on fine needle
      aspiration cytology. The patient underwent Lutetium (Lu)-labeled PSMA radioligand
      therapy, which also revealed diffuse tracer uptake in the penile shaft as well as
      other metastatic sites.

PMID- 29465494
TI  - 68Ga-PSMA PET/CT Revealing Unusual Inguinal Canal and Distant Nodal Metastasis in
      a Case of Castration-Resistant Prostate Cancer.
AB  - Gallium-prostate-specific membrane antigen (Ga-PSMA) is well established in the
      imaging of prostate cancer (PC). Here, we report a case of castration-resistant
      PC who underwent Ga-PSMA PET/CT for recurrence evaluation, which revealed
      metastatic lesions in distant lymph nodes and additionally an unusual metastatic
      deposit in the inguinal canal. The second Ga-PSMA PET/CT done after oral hormonal
      therapy yielded a favorable response. This pattern of distant metastatic spread
      is a rare presentation of PC, and PSMA PET/CT revealed the unusual metastasis in
      the inguinal canal with a timely therapy culminating in favorable disease
      response.

PMID- 29465496
TI  - A Systematic Review of Exercise Training in Patients With Cardiac Implantable
      Devices.
AB  - PURPOSE: This systematic review identified exercise-based intervention studies in
      patients with cardiac implantable devices (CIDs): implantable cardioverter
      defibrillator (ICD), cardiac resynchronization pacemaker or defibrillator
      (cardiac resynchronization therapy [CRT]), or ventricular assist device (VAD) and
      assessed evidence for the safety and efficacy of exercise-based interventions
      alone or in combination with psychoeducational components. METHODS: PubMed,
      EMBASE, CINAHL Plus, Web of Science, Cochrane, and PEDro databases were searched
      from database inception to September 2016. Data were extracted and validity was
      assessed by 2 reviewers. Study quality was evaluated using the JADAD scale for
      randomized controlled trials. A total of 3991 articles for all CIDs (ICD: 1015;
      pacemaker: 1630; and VAD: 1346) were screened for relevance. Subsequently, 24
      full-text articles (ICD: 14; CRT: 4; and VAD: 6) were deemed eligible for this
      review. RESULTS: Studies of aerobic exercise training demonstrated an average
      increase in peak oxygen uptake of 2.61 mL/kg/min, (ICD = 2.43, VAD = 2.2, and CRT
      = 3.2 mL/kg/min). These incremental increases were statistically significant when
      compared with the usual care or other comparison groups. Adverse event rates were
      very low at 1.1% to 2.2% for all CIDs. CONCLUSION: Exercise interventions tested
      to date in the CID population (ICD, CRT, and VAD) indicate that exercise training
      at moderate to high intensity is safe and effective in improving cardiopulmonary
      outcomes without adverse events. Future investigations should include a more
      diverse sample of participants, designs that include translation of exercise to
      routine practice, the destination therapy VAD population, and measurement of
      costs and patient-centered outcomes.

PMID- 29465495
TI  - Exercise Rehabilitation for Peripheral Artery Disease: A REVIEW.
AB  - PURPOSE: To summarize evidence regarding exercise therapy for people with lower
      extremity peripheral artery disease (PAD). METHODS: Literature was reviewed
      regarding optimal strategies for delivering exercise interventions for people
      with PAD. Randomized trial evidence and recent studies were emphasized. RESULTS:
      Randomized clinical trial evidence consistently demonstrates that supervised
      treadmill exercise improves treadmill walking performance in people with PAD. A
      meta-analysis of 25 randomized trials (1054 participants) concluded that
      supervised treadmill exercise was associated with 180 m of improvement in maximal
      treadmill walking distance and 128 m of improvement in pain-free walking distance
      compared with a control group. Three randomized trials of 493 patients with PAD
      demonstrated that home-based walking exercise interventions that incorporate
      behavioral change techniques improve walking ability in patients with PAD.
      Furthermore, evidence suggests that home-based walking exercise improves the 6
      min walk more than supervised treadmill exercise. Upper and lower extremity
      ergometry also significantly improved walking endurance in PAD. The Centers for
      Medicare & Medicaid Services recently determined that Medicare would cover 12 wk
      (36 sessions) of supervised treadmill exercise for patients with PAD.
      CONCLUSIONS: Supervised treadmill exercise and home-based walking exercise each
      improve walking ability in patients with PAD. The availability of insurance
      coverage for supervised treadmill exercise for patients with PAD will make
      supervised treadmill exercise more widely available and accessible. Home-based
      exercise that incorporates behavioral change technique is an effective
      alternative for patients unwilling or unable to attend 3 supervised exercise
      sessions per week.

PMID- 29465497
TI  - Effects of beta-Blockers on Maximal Heart Rate Prediction Equations in a Cardiac
      Population.
AB  - PURPOSE: To derive specific maximal heart rate (HRmax) prediction equations for a
      coronary artery disease (CAD) population based upon status of beta-blocker (BB)
      therapy and to compare these to prior HRmax equations (Fox and Brawner-specific
      for CAD). METHODS: We retrospectively reviewed stress echocardiogram treadmill
      tests in patients with CAD, dividing subjects into 3 groups based upon BB use on
      test day: not prescribed BB therapy (no BB group; n = 110); held for 12 to 24 hr
      prior (held BB group; n = 155); and continued taking (took BB group; n = 72).
      RESULTS: Derived HRmax equations for our CAD population were no BB = 200 - 0.79 *
      age; held BB = 193 - 0.71 * age; and took BB = 168 - 0.51 * age. Achieved HRmax
      mean was not significantly different between held BB and no BB groups; however,
      HRmax in the took BB group was significantly lower. Fox and Brawner (no BB)-HRmax
      equations significantly overestimated (+6 and +9 mean bias) and underestimated (
      8 and -6 mean bias) achieved HRmax in no BB and held BB groups, respectively. The
      Brawner (no BB) equation intercept and slope were not significantly different
      from our CAD-held BB and no BB equations. The Brawner (on BB) equation intercept
      and slope were similar to our took BB equation, but greatly underestimated
      achieved HRmax (-17 mean bias). CONCLUSION: For patients holding BB therapy on
      test day, a similar CAD HRmax estimation equation to those patients never on BB
      can be used, comparable to the Brawner (no BB) equation. Further research is
      needed to determine when patients should take their BB therapy in conjunction
      with exercise testing.

PMID- 29465498
TI  - Variability in Quality of Life Outcomes Following a Pulmonary Rehabilitation
      Program in Patients With COPD.
AB  - PURPOSE: Pulmonary rehabilitation (PR) improves exercise tolerance in patients
      with chronic obstructive pulmonary disease. However, it is unclear why some
      patients do not improve quality of life during a training program. Our objective
      was to evaluate the differences between patients with chronic obstructive
      pulmonary disease who improve and those who do not improve quality of life during
      a pulmonary rehabilitation program. METHODS: Seventy-three patients underwent a
      PR program. All patients trained at 80% (legs) and 50% (arms) of their maximum
      load. Incremental and endurance tests, 6-min walk test, and health-related
      quality of life with the St George Respiratory Questionnaire (SGRQ) were
      measured. We subdivided the groups based on a decrease >=4 points in the pre- and
      post-PR SGRQ total score (G1); <4-point change in the SGRQ total score (G2); and
      an increase in scores >=4 points (G3). RESULTS: Exacerbation frequency (P = .004)
      and SGRQ total scores (P < .001) were lower in G1 and G2 than in G3. G1 (P =
      .0007) and G2 (P = .0005) significantly improved 6-min walk test distance. Before
      PR, G1 and G2 walked greater distances than G3 (P = .003); however, the
      difference was no longer significant after PR (P = .34). A significant load
      increase was seen after PR for the 3 groups (P < .05). We found a significant
      correlation between the SGRQ and the Charlson index (r = 0.78, P < .0001),
      exacerbation frequency (r = 0.72, P < .0001), and basal dyspnea index (r = -0.48,
      P < .0001). CONCLUSION: Patients whose quality of life did not improve after
      comprehensive PR presented a higher number of disease-related exacerbations with
      comorbidities.

PMID- 29465499
TI  - Pulmonary Rehabilitation in Patients With Advanced Idiopathic Pulmonary Fibrosis
      Referred for Lung Transplantation.
AB  - PURPOSE: Currently, pulmonary rehabilitation (PR) has a weak recommendation for
      idiopathic pulmonary fibrosis (IPF) and is often recommended for mild to moderate
      disease. We aimed to investigate the completion rate of PR in patients with
      advanced IPF, to analyze whether the severity of disease influences PR response
      and whether there is any difference between subjects who are able or not able to
      successfully complete the program. METHODS: Patients with IPF referred to lung
      transplantation (n = 48) were enrolled in an outpatient PR program including 3
      times/wk supervised exercise training during 12 wk. A short-form 36-item health
      related quality-of-life (HRQL) questionnaire and 6-min walk test distance (6MWD)
      were evaluated before and after PR. RESULTS: We found that 64.5% of patients
      successfully completed PR (31/48). Baseline forced vital capacity (FVC) and lung
      diffusion capacity for carbon monoxide (DLCO) were 49% +/- 13% and 46% +/- 17% of
      predicted, respectively. There was no difference comparing those who did and did
      not complete PR. In the former group, 6MWD (58 +/- 63 m) and several domains of
      the HRQL questionnaire improved significantly. No significant association was
      found between markers of disease severity (FVC, DLCO, and dyspnea) and
      improvement in clinical outcomes. CONCLUSIONS: Two-thirds of our sample with
      advanced IPF referred to lung transplant successfully attended PR and improved
      exercise capacity and HRQL, without association with markers of disease severity.
      No difference was found at baseline compared with subjects who were not able to
      complete the program.

PMID- 29465501
TI  - Experience, Knowledge, and Attitudes of Child and Adolescent Psychiatrists in
      Belgium Toward Pediatric Electroconvulsive Therapy.
AB  - OBJECTIVE: The purpose of the present study was to ascertain the experience,
      knowledge, and attitudes of child and adolescent psychiatrists toward the use of
      ECT (electroconvulsive therapy) in children and adolescents in Belgium. METHODS:
      A questionnaire was mailed to all the members of the Flemish and Walloon
      Association of Child and Adolescent Psychiatrists. RESULTS: Thirty-five percent
      (n = 151) of the psychiatrists responded to the questionnaire. Sixty-seven
      percent (n = 101) rated their knowledge about ECT in children and adolescents as
      nil or negligible. Only one percent (n = 2) estimated their knowledge to be
      advanced. Fifteen percent (n = 22) were aware of a minor treated with ECT. Ten (n
      = 16) and thirty-one percent (n = 47) believed that ECT is a safe treatment for
      children and adolescents, respectively. Only six percent (n = 10) would recommend
      ECT for a major psychiatric disorder in a child, whereas thirty-eight percent (n
      = 58) for an adolescent. Fifty-three percent (n = 71) regarded ECT as a treatment
      of last resort. A significant correlation was identified between knowledge and
      attitudes toward the use of ECT in minors. Respondents with some or advanced
      knowledge perceived ECT as a safer and a more effective treatment option than
      those with negligible knowledge. Most (91%, n = 138) of the child and adolescent
      psychiatrists are enthusiastic to learn more about the use of ECT in minors.
      CONCLUSIONS: Flemish and Walloon child and adolescents psychiatrists have very
      little experience with using ECT in minors. They self-estimated their knowledge
      as negligible but are keen to learn more about this treatment option. The lack of
      knowledge likely explains the rare use of ECT in Belgium for children and
      adolescents with serious psychiatric disorders.

PMID- 29465503
TI  - Body composition and bone mineral density after ovarian hormone suppression with
      or without estradiol treatment: Erratum.

PMID- 29465502
TI  - Ultrasound in menopause: a look back.

PMID- 29465504
TI  - Letter From the Editor.

PMID- 29465505
TI  - Mutational Aberrations Detected in Mucinous Epithelial Ovarian Cancer of Asian
      Women.
AB  - BACKGROUND: Mucinous epithelial ovarian cancers (mEOCs) respond poorly to
      conventional chemotherapy and have a poor prognosis in advanced stages. The
      genomic landscape for mEOC in the Asian settings is ill defined. We seek to
      identify various mutational aberrations present in mEOC and correlate them with
      clinical outcomes. METHODS: A total of 199 cases of mEOC were identified from a
      prospectively maintained gynecologic oncology tumor database. DNA was extracted
      and analyzed for KRAS mutations by using Sanger sequencing. Further MassArray
      sequencing was performed on 45 samples. Clinicopathologic correlation was
      performed with the results obtained. FINDINGS: KRAS mutation status was evaluable
      in 124 cases. Fifty-five percent (68/124) were KRAS negative, whereas 45%
      (56/124) harbored a KRAS mutation, lower than that in Western populations.
      Successful ascertainment of both KRAS and HER2 statuses by Sanger sequencing
      occurred for 105 cases. The proportion of the double-positive subtype (HER2+ and
      KRAS positive) was 8% (8/105); double-negative subtype (HER2- and KRAS negative),
      34% (36/105); and cases with mutation in either KRAS or HER2, 58% (61/105). The
      KRAS mutation rate was 44%, 50%, and 29% among Chinese, Indians, and Malays,
      respectively. There was no significant difference in overall survival (P = 0.952)
      or progression-free survival (P = 0.635) between KRAS-positive and KRAS-negative
      patients. Similar results were observed for progression-free survival (P = 0.206)
      and overall survival (P = 0.440) when outcomes were examined between the 4 groups
      based on KRAS and HER2 mutation. Patients in the double-negative mutation
      subgroup had higher risk for death/progression compared with patients in the
      other 3 mutation subgroups. Further MassARRAY multiplexed profiling was performed
      in patients with sufficient DNA material (n = 45) and yielded KRAS mutations (n =
      16), PDGFRA mutations (n = 3), PIK3CA (n = 1) and KIT (n = 1), and HRAS, FGFR,
      MET, and NRAS (n = 1 each). CONCLUSIONS: Our study provides further knowledge
      about the mutational aberrations in mEOC in Asian populations. Neither the
      presence of KRAS mutation nor their correlation with HER2 mutations influenced
      outcomes.

PMID- 29465506
TI  - BRCA1, Ki67, and beta-Catenin Immunoexpression Is Not Related to Differentiation,
      Platinum Response, or Prognosis in Women With Low- and High-Grade Serous Ovarian
      Carcinoma.
AB  - OBJECTIVE: The purpose of this study was to compare the immunohistochemical
      expression of BRCA1, Ki67, and beta-catenin in women with low-grade (LGSOC) and
      high-grade serous ovarian carcinomas (HGSOC) and their relationship with
      clinicopathological features, response to platinum-based chemotherapy, and
      survival. METHODS: For this study, 21 LGSOC and 85 HGSOC stage I to IV cases,
      diagnosed and treated from 1996 to 2013 and followed-up until December 2016, were
      included. BRCA1, Ki67, and beta-catenin expression was assessed using tissue
      microarray-based immunohistochemistry. RESULTS: Women with HGSOC were
      significantly more likely to have advanced-stage disease (P < 0.001), higher
      CA125 levels (P < 0.001), postsurgery residual disease (P < 0.01), and higher
      rates of disease progression and recurrence (P = 0.001). The percentage of women
      with HGSOC whose tumors expressed Ki67 was significantly higher compared with
      women with LGSOC (P < 0.001). The expression of BRCA1 and beta-catenin did not
      differ between LGSOC and HGSOC (P = 0.12 and P = 1.00, respectively). The
      clinicopathological features and the response to platinum-based chemotherapy did
      not differ according to the BRCA1, Ki67, and beta-catenin expression in either
      group. In HGSOC, only International Federation of Gynecology and Obstetrics stage
      was independently associated with poor survival (PFS and OS). CONCLUSIONS: Ki67
      expression was significantly higher in HGSOC. BRCA1 and beta-catenin expression
      did not differ between LGSOC and HGSOC samples. BRCA1, Ki67, and beta-catenin
      expression was neither related to clinicopathological features, response to
      platinum-based chemotherapy, nor survival. Only International Federation of
      Gynecology and Obstetrics stage remained associated with poor survival in women
      with HGSOC.

PMID- 29465507
TI  - BRCA1 and MAD2 Are Coexpressed and Are Prognostic Indicators in Tubo-ovarian High
      Grade Serous Carcinoma.
AB  - OBJECTIVES: The aim of this study was to investigate the relationship between
      BRCA1 and mitotic arrest deficiency protein 2 (MAD2) protein expression, as
      determined by immunohistochemistry, and clinical outcomes in epithelial ovarian
      carcinoma (EOC). METHODS: A tissue microarray consisting of 94 formalin-fixed
      paraffin-embedded EOC with fully matched clinicopathological data were
      immunohistochemically stained with anti-BRCA1 and anti-MAD2 antibodies. The cores
      were scored in a semiquantitative manner evaluating nuclear staining intensity
      and extent. Coexpression of BRCA1 and MAD2 was evaluated, and patient survival
      analyses were undertaken. RESULTS: Coexpression of BRCA1 and MAD2 was assessed in
      94 EOC samples, and survival analysis was performed on 65 high-grade serous
      carcinomas (HGSCs). There was a significant positive correlation between BRCA1
      and MAD2 expression in this patient cohort (P < 0.0001). Both low BRCA1 and low
      MAD2 are independently associated with overall survival because of HGSC. Low
      coexpression of BRCA1 and MAD2 was also significantly associated with overall
      survival and was driven by BRCA1 expression. CONCLUSION: BRCA1 and MAD2
      expressions are strongly correlated in EOC, but BRCA1 expression remains the
      stronger prognostic factor in HGSC.

PMID- 29465509
TI  - Increased Endothelial Progenitor Cell Number in Early Stage of Endometrial
      Cancer: Erratum.

PMID- 29465508
TI  - Impact of Hormone Receptor Status and Ki-67 Expression on Disease-Free Survival
      in Patients Affected by High-risk Endometrial Cancer.
AB  - OBJECTIVES: The aim of this study was to evaluate the immunohistochemical (IHC)
      expression of Ki-67, estrogen receptors alpha (ERsalpha), and progesterone
      receptors (PRs) in high-risk endometrial cancer patients and to assess their
      prognostic impact. METHODS/MATERIALS: Immunohistochemical expression of Ki-67,
      ERsalpha, and PRs was evaluated in primary untreated endometrial cancer. The
      correlation among IHC staining and risk factors of recurrence such as age,
      Federation International of Gynecology and Obstetrics stage, grading, depth of
      invasion, and metastatic spread was assessed. RESULTS: Eighty-two patients were
      available for the analysis. Mean +/- SD age was 65.05 +/- 10.48 years. The IHC
      assessment revealed a lack of ERalpha in 46.3% and of PR in 48.7% as well as a
      high Ki-67 in 31.7%. Loss of ERalpha and PR was associated with a significant
      higher rate of advanced stage of disease, a higher frequency of G3 tumors, and a
      myometrial invasion greater than 50%. A strong Ki-67 expression correlated with a
      deeper myometrial invasion. Analysis of the interrelationship between receptor
      immunonegativity revealed a relevant association of ERalpha immunolocalization
      with PR and with a high Ki-67 expression. The present study also showed that loss
      of ERalpha (P = 0.003), advanced Federation International of Gynecology and
      Obstetrics stage (P < 0.001), and high Ki-67 (P = 0.004) were independent
      prognostic factors of a shorter disease-free survival. Importantly, loss of
      ERalpha, loss of PR, and a high Ki-67 were correlated with a higher incidence of
      distant recurrence. CONCLUSIONS: A systematic immunohistochemistry should be a
      key step in the therapeutic algorithm and could contribute to the identification
      of high-risk tumors.

PMID- 29465510
TI  - Chronic Rhinosinusitis Related to Occupational Exposure: The Telemark Population
      Study.
AB  - OBJECTIVE: The aim of this study was to investigate the association between
      occupational exposure and chronic rhinosinusitis. METHODS: A random population
      from the region of Telemark, aged 16 to 50 years, answered a respiratory
      questionnaire including questions on chronic rhinosinusitis and exposure in the
      occupational environment. RESULTS: A total of 16,099/48,142 subjects responded.
      The prevalence of chronic rhinosinusitis was 9%. Exposure associated with chronic
      rhinosinusitis comprised paper dust [odds ratio (OR) 1.3, 95% confidence interval
      (95% CI) 1.1 to 1.5], cleaning agents (OR 1.2, 95% CI 1.0 to 1.3), metal dust (OR
      1.3, 95% CI 1.1 to 1.6), animals (OR 1.2, 95% CI 1.0 to 1.5),
      moisture/mould/mildew (OR 1.3, 95% CI 1.1 to 1.5), and physically strenuous work
      (OR 1.4, 95% CI 1.2 to 1.7). CONCLUSION: Occupational exposure to paper dust,
      cleaning agents, metal dust, animals, moisture/mould/mildew, and physically
      strenuous work was independently related to having chronic rhinosinusitis. An
      occupational history should be reviewed when assessing patients with chronic
      rhinosinusitis.

PMID- 29465511
TI  - Prescription Dispensing Patterns Before and After a Workers' Compensation Claim:
      An Historical Cohort Study of Workers With Low Back Pain Injuries in British
      Columbia.
AB  - OBJECTIVE: Compare prescription dispensing before and after a work-related low
      back injury. METHODS: Descriptive analyses were used to describe opioid,
      nonsteroidal anti-inflammatory drug (NSAID), and skeletal muscle relaxant (SMR)
      dispensing 1 year pre- and post-injury among 97,124 workers in British Columbia
      with new workers' compensation low back claims from 1998 to 2009. RESULTS: Before
      injury, 19.7%, 21.2%, and 6.3% were dispensed opioids, NSAIDs, and SMRs,
      respectively, increasing to 39.0%, 50.2%, and 28.4% after. Median time to first
      post-injury prescription was less than a week. Dispensing was stable pre-injury,
      followed by a sharp increase within 8 weeks post-injury. Dispensing dropped
      thereafter, but remained elevated nearly a year post-injury, an increase
      attributable to less than 2% of claimants. CONCLUSION: These drug classes are
      commonly dispensed, particularly shortly after injury and dispensing is of short
      duration for most, though a small subgroup receives prolonged courses.

PMID- 29465513
TI  - Health Care Expenditures and Length of Disability Across Medical Conditions.
AB  - OBJECTIVE: To describe the relationship between the length of short-term
      disability (STD) and health care spending. METHODS: Medical claims for insured US
      employees on STD were evaluated to describe the distribution of disability
      durations and health expenditures across major diagnostic categories and common
      medical conditions. Correlations between health expenditures and disability
      durations were examined. RESULTS: The most expensive 10% of cases accounted for
      more than half of total health spending. The longest 10% of cases accounted for
      more than one-third of total disability time. Only one-third of the most
      expensive cases were also among the longest in duration. Disability durations
      were moderately correlated with medical spending and this relationship was
      modified by comorbid conditions and age. CONCLUSION: Psychosocial barriers, in
      addition to biomedical factors, should be considered to achieve optimal
      functional outcomes and well-being of patients.

PMID- 29465512
TI  - MicroRNA Changes in Firefighters.
AB  - OBJECTIVES: Firefighters have elevated cancer incidence and mortality rates.
      MicroRNAs play prominent roles in carcinogenesis, but have not been previously
      evaluated in firefighters. METHODS: Blood from 52 incumbent and 45 new recruit
      nonsmoking firefighters was analyzed for microRNA expression, and the results
      adjusted for age, obesity, ethnicity, and multiple comparisons. RESULTS: Nine
      microRNAs were identified with at least a 1.5-fold significant difference between
      groups. All six microRNAs with decreased expression in incumbent firefighters
      have been reported to have tumor suppressor activity or are associated with
      cancer survival, and two of the three microRNAs with increased expression in
      incumbent firefighters have activities consistent with cancer promotion, with the
      remaining microRNA associated with neurological disease. CONCLUSION: Incumbent
      firefighters showed differential microRNA expression compared with new recruits,
      providing potential mechanisms for increased cancer risk in firefighters.

PMID- 29465514
TI  - Smoking Cessation Is Associated With Lower Indirect Costs.
AB  - OBJECTIVE: This study quantified differences in indirect costs due to decreased
      work productivity between current and former smokers. Former smokers were further
      categorized by number of years since quitting to assess corresponding
      differences. METHODS: Data on employed individuals were obtained from the 2013 US
      National Health and Wellness Survey (NHWS; N = 75,000). Indirect costs were
      calculated for current smokers and former smokers from weekly wages based on age
      and sex. RESULTS: The annual total indirect costs for current smokers were
      $1327.53, $1560.18, and $1839.87 higher than for those who quit 0 to 4 years, 5
      to 10 years, and more than or equal to 11 years prior, respectively. There were
      no significant differences in mean total indirect costs between the former smoker
      groups. CONCLUSIONS: Current smokers showed significantly higher total annual
      indirect costs compared with former smokers, independently of the number of years
      since quitting smoking.

PMID- 29465515
TI  - Metabolic Rate during a Cognitive Vigilance Challenge at Alternative
      Workstations.
AB  - OBJECTIVE: The aim of this study was to compare energy expenditure (EE, kcal/min)
      at three workstations during an attention-demanding cognitive function task (Test
      of Variables of Attention or TOVA). Workstations included the seated desk (SIT),
      standing desk (STAND), and seated workstation designed to promote spontaneous
      movement (SWING). METHODS: Adult males (n = 11) and females (n = 13) were
      assessed for EE using VO2 and VCO2 per quarter of the 22-min TOVA. RESULTS:
      Average EE were 1.39 +/- 0.06 (SIT), 1.55 +/- 0.08 (SWING), and 1.44 +/- 0.08
      (STAND). Main effects (P < 0.05) were seen for workstation (SWING, STAND > SIT),
      and quarter of TOVA (Q2 < Q1,Q3,Q4). TOVA errors and response times were not
      different for workstations but increased for Q3 and Q4. CONCLUSION: Spontaneous
      movement at an alternative workstation elevated EE 10% to 11% compared with
      sitting and could increase daily nonexercise activity thermogenesis without
      diminishing mental attention to desk work.

PMID- 29465517
TI  - Letters.

PMID- 29465519
TI  - Know what you're getting into: The cost of remedy and reward.

PMID- 29465516
TI  - The Correlation of a Corporate Culture of Health Assessment Score and Health Care
      Cost Trend.
AB  - OBJECTIVE: Employers that strive to create a corporate environment that fosters a
      culture of health often face challenges when trying to determine the impact of
      improvements on health care cost trends. This study aims to test the stability of
      the correlation between health care cost trend and corporate health assessment
      scores (CHAS) using a culture of health measurement tool. METHODS: Correlation
      analysis of annual health care cost trend and CHAS on a small group of employers
      using a proprietary CHAS tool. RESULTS: Higher CHAS scores are generally
      correlated with lower health care cost trend. For employers with several years of
      CHAS measurements, this correlation remains, although imperfectly. CONCLUSION: As
      culture of health scores improve, health care costs trends moderate. These
      findings provide further evidence of the inverse relationship between
      organizational CHAS performance and health care cost trend.

PMID- 29465521
TI  - One patient experience inspires nursing staff caring for dying patients.

PMID- 29465522
TI  - What nurses should know about online programs.

PMID- 29465524
TI  - Screening and brief intervention to prevent fetal alcohol spectrum disorders.

PMID- 29465525
TI  - How oral medications affect wound healing.

PMID- 29465526
TI  - Clara Barton: Angel of the battlefield.

PMID- 29465527
TI  - What does the evidence say about the Mediterranean diet?

PMID- 29465528
TI  - Supporting coworkers after a personal loss.

PMID- 29465529
TI  - Preventing suicide beyond psychiatric units.

PMID- 29465530
TI  - CRE infection: Sorting out patient-care complexities.

PMID- 29465531
TI  - Novice nursing research: Walking in our shoes.

PMID- 29465533
TI  - Online resources for patients with ovarian cancer.

PMID- 29465532
TI  - Should your patient be PrEPared?

PMID- 29465535
TI  - Implementing bedside shift report: Walking the walk and talking the talk.

PMID- 29465536
TI  - Primary cutaneous amyloidosis associated with autoimmune hepatitis-primary
      biliary cirrhosis overlap syndrome and Sjogren syndrome: A case report.
AB  - RATIONALE: Primary cutaneous amyloidosis (PCA) is a localized skin disorder
      characterized by the abnormal deposition of amyloid in the extracellular matrix
      of the dermis. The association between PCA and other diseases, although rare, has
      been documented for various autoimmune diseases. PCA associated with autoimmune
      hepatitis-primary biliary cirrhosis (AIH-PBC) overlap syndrome and Sjogren
      syndrome (SS) has not been previously reported in the literature. PATIENT
      CONCERNS: A 50-year-old woman presented with progressive abnormal liver enzyme
      levels and was referred to our department. DIAGNOSES: Due to the patient's
      symptoms, laboratory test results, radiographic findings, and pathologic results,
      she was diagnosed with PCA associated with AIH-PBC overlap syndrome and SS.
      INTERVENTIONS: She was subsequently treated with a combination of ursodeoxycholic
      acid (UDCA), prednisone, and azathioprine. OUTCOMES: While this treatment can
      achieve therapeutic success, it cannot prevent complications from cirrhosis. This
      patient remains alive but experienced an emergent gastrointestinal hemorrhage.
      LESSONS: While we acknowledge that this is a single case, these findings extend
      our knowledge of immunological diseases associated with PCA and suggest a common,
      immune-mediated pathogenic pathway between PCA, AIH-PBC overlap syndrome, and SS.
      After 12 years of follow up, clinical manifestations have developed, and these
      autoimmune diseases have progressed. The combination of UDCA, prednisone, and
      azathioprine can achieve therapeutic success but cannot prevent disease
      progression. Routine follow up for this patient is necessary to document disease
      progression.

PMID- 29465538
TI  - Enhanced recovery after surgery (ERAS) programs for esophagectomy protocol for a
      systematic review and meta-analysis.
AB  - BACKGROUND: Esophageal cancer is one of the worst malignant digestive neoplasms
      with poor treatment outcomes. Esophagectomy plays an important role and offers a
      potential curable chance to these patients. However, esophagectomy with radical
      lymphadenectomy is known as one of the most invasive digestive surgeries which
      are associated with high morbidity and mortality. The enhanced recovery after
      surgery (ERAS) protocol is a patient-centered, surgeon-led system combining
      anesthesia, nursing, nutrition, and psychology, which is designed for reducing
      complications, promoting recovery, and improving treatment outcomes. This
      systematic review and meta-analysis is aiming at how beneficial, and to what
      extent ERAS really will be. METHODS: A systematic literature search will be
      performed through January 2018 using MEDLINE, EMBASE, the Cochrane Central
      Register of Controlled Trials, and Google Scholar for relevant articles published
      in any language. Randomized controlled trials, prospective cohort studies, and
      propensity-matched comparative studies will be included. All meta-analyses will
      be performed using Review Manager software. The quality of the studies will be
      evaluated using the guidelines listed in the Cochrane Handbook. The Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses statements will be
      followed until the findings of the systematic review and meta-analysis are
      reported. RESULTS: The results of this systematic review and meta-analysis will
      be published in a peer-reviewed journal. CONCLUSION: Our study will draw an
      objective conclusion of the comparisons between ERAS and conventional care in
      aspects of perioperative outcomes and provide level I evidences for clinical
      decision makings.

PMID- 29465537
TI  - Laparoscopic gastrectomy for elderly patients with gastric cancer: A systematic
      review with meta-analysis.
AB  - BACKGROUND: Laparoscopic gastrectomy (LG) has been widely applied in patients
      with gastric cancer (GC). However, the safety and application value of LG in
      elderly patients with GC was still unclear. In this study, we aimed to evaluate
      the feasibility and safety of LG for elderly patients with GC using the meta
      analysis. METHODS: Studies comparing elderly patients and nonelderly patients who
      underwent LG for GC were reviewed and collected from the PubMed, EBSCO, Cochrane
      Library, and EMBASE. Outcomes such as operative results, postoperative recovery,
      and morbidity were compared and analyzed. The Review Manager 5.3 was used to
      portray the weighted mean difference (WMD) and odds ratio (OR) with a 95%
      confidence interval (CI). RESULTS: Eleven observational studies with a total of
      3275 patients were included. Compared with nonelderly patients, elderly patients
      had shorter operation time (WMD -10.46; 95% CI -17.06 to -3.86; P = .002), less
      retrieved lymph nodes (WMD -2.34; 95% CI -3.77 to -0.92; P = .001), delayed time
      to first flatus (WMD 0.31; 95% CI 0.10-0.51; P = .003), longer postoperative
      hospital stays (WMD 1.06; 95% CI 0.07-2.05; P = .04), higher risk for overall
      postoperative complication (OR 1.34; 95% CI 1.08-1.67; P = .009), nonsurgical
      postoperative complication (OR 1.98; 95% CI 1.24-3.15; P = .004), and
      postoperative pulmonary complication (OR: 3.09; 95% CI 1.68-5.68; P < .001).
      There was no significance between nonelderly patients and elderly patients
      regarding the estimated blood loss, incidences of surgical postoperative
      complication, surgical site infection, and ileus (P > .05). CONCLUSION: Outcomes
      of LG for elderly patients were comparable to those in nonelderly patients. Age
      alone should not preclude LG in elderly patients.

PMID- 29465540
TI  - Clostridium difficile infection in hospitalized patients with inflammatory bowel
      disease: Prevalence, risk factors, and prognosis: Erratum.

PMID- 29465539
TI  - Different utilization of intensive care services (ICSs) for patients dying of
      hemorrhagic and ischemic stroke, a hospital-based survey.
AB  - The intensive care service (ICS) saves lives and rescues the neurological
      function of stroke patients. We wondered the different utilization of ICS for
      patients with ischemic and hemorrhagic stroke, especially those who died within
      30 days after stroke.Sixty-seven patients died during 2011 to 2015 due to acute
      stroke (42 due to intracranial hemorrhage [ICH]; 25 due to cerebral infarct
      [CI]). The durations of hospital stay (hospital staying days [HSDs]) and ICS
      staying days (ISDs) and codes of the do-not-resuscitate (DNR) were surveyed among
      these medical records. Statistics included chi-square and descriptive analyses.In
      this study, CI patients had a longer HSD (mean 14.3 days), as compared with ICH
      patients (mean 8.3 days); however, the ICH patients had a higher percentage of
      early entry within the first 24 hours of admission into ICS than CI group (95.1%
      vs 60.0%, P = .003). A higher rate of CI patients died in holidays or weekends
      than those with ICH (44.0% vs 21.4%, P = .051). DNR, requested mainly from direct
      descendants (children or grandchildren), was coded in all 25 CI patients (100.0%)
      and 38 ICH patients (90.5%). More cases with early DNR coded within 24 hours
      after admission occurred in ICH group (47%, 12% in CI patients, P = .003). None
      of the stroke patient had living wills. Withhold of endotracheal intubation (ETI)
      occurred among CI patients, more than for ICH patients (76.0% vs 18.4%, P <
      .005).In conclusion, CI patients longer HSD, ISD, higher mortality within
      holidays or weekends, and higher ETI withhold; but less percentage of ICS
      utilization expressed by a lower ISD/HSD ratio. This ICS utilization is a key
      issue of medical quality for stroke care.

PMID- 29465541
TI  - Abnormal glucose regulation in Chinese patients with coronary artery disease: A
      cross-sectional study: Erratum.

PMID- 29465543
TI  - Spontaneous reattachment of Descemet membrane detachment after deep anterior
      lamellar keratoplasty: A case report.
AB  - RATIONALE: To report a case of late spontaneous reattachment of Descemet membrane
      (DM) detachment after deep anterior lamellar keratoplasty (DALK). PATIENT
      CONCERNS: A 50-year-old woman with stromal corneal scarring underwent a DALK with
      the big bubble technique. The DM detachment and double anterior chamber were
      observed on the first day after operation. DIAGNOSES: Descemet membrane
      detachment after deep anterior lamellar keratoplasty [Oculus Dexter (OD),
      indicates right eye]. INTERVENTIONS: Sterile air injection was unsuccessful.
      Conservative observation was performed. OUTCOMES: During the follow-up, the donor
      cornea kept transparent and no edema was observed. The DM reattached
      spontaneously at the fifth months post-DALK. LESSONS: The present case suggests
      that the retained host DM may result in DM detachment after DALK. For the DM
      detachment without roll rim, the detachment may spontaneously reattach in several
      months after surgery.

PMID- 29465542
TI  - The small bowel diseases detected by capsule endoscopy in patients with chronic
      abdominal pain: A retrospective study.
AB  - Chronic abdominal pain (CAP) remains a particular challenge because of its
      complicated causes, especially when the disorders involve the small bowel, where
      it is quite difficult to intubate the flexible endoscopes. This study was to
      investigate the small bowel diseases detected by capsule endoscopy (CE) in CAP
      patients to evaluate the role of CE on CAP, and analyzed the relationship among
      the clinical characteristics of CAP patients and the positive rates of CE
      findings to search for the indications of CE for CAP patients.This retrospective
      study included 341 patients with CAP defined as recurrent abdominal pain for no
      <3 months. Each patient underwent CE after a negative diagnostic work-up. All CE
      images were reviewed by 3 gastroenterologists independently. The positive
      findings were defined as abnormal findings in the small bowel that might have
      been the causes of CAP. The final diagnosis was confirmed by CE findings,
      clinical features, histopathology, and a response to the treatment during the
      follow-up for at least 3 months after CE.The overall positive rate of CE findings
      was 28.15% (96/341). The positive rate in CAP-A (CAP with associated symptoms)
      group was significantly higher than that in CAP-O (CAP only) group (33.16% vs
      21.38%, P = .017). Multivariate logistic regression analysis revealed that weight
      loss (odds ratio [OR] = 2.827, 95% confidence interval (CI) = 1.938-4.926),
      hypoalbuminemia (OR = 6.142, 95%IC = 4.129-8.274), elevated erythrocyte
      sedimentation rate (ESR) (OR = 4.025, 95%IC = 3.178-6.892), or increased C
      reactive protein (CRP) (OR = 7.539, 95%CI = 5.365-11.723) were significantly
      associated with high positive rates. On follow-up, final diagnosis was confirmed
      in 56 of 69 (81.16%) patients with positive CE findings. About half of these
      patients (46.38%, 32/69) were diagnosed as inflammatory diseases, including Crohn
      disease (12), tuberculosis (5), NSAID enteropathy (4), etc. Tumors were proved in
      21.74% (15/69) patients, including malignant in 7 cases and benign in 8 cases.
      Parasitosis was found in 9 (13.04%) patients.This study suggests that CE may be
      helpful for CAP patients to detect the small bowel diseases, half of which were
      comprised of inflammatory diseases. Besides, weight loss, hypoalbuminemia,
      elevated ESR, or increased CRP may be regarded as the indications of CE for CAP
      patients.

PMID- 29465544
TI  - The choose of different surgical therapies of hepatic alveolar echinococcosis: A
      single-center retrospective case-control study.
AB  - The aim of this study was to evaluate different surgical therapies for hepatic
      alveolar echinococcosis in different clinical stages.We analyze the clinical data
      of 115 patients who received surgical treatment in West China Hospital from
      January 2004 to June 2016. Among these patients, 77 cases underwent radical
      hepatic resection (group A, n = 77); 17 cases underwent palliative resection
      (group B, n = 17), and 21 cases underwent liver transplantation (group C, n = 21)
      with 12 cases of orthotopic liver transplantation and 9 cases of liver
      autotransplantation.The postoperative complication rate of radical hepatic
      resection group was 13.0% (10/77), which is statistically significant (P < .05)
      than the rate of palliative resection group 29.4% (5/17) or liver transplantation
      group 23.8% (5/21). The follow-up period ranged from 1 to 72 months. The overall
      median survival rate of radical resection was 72/77, higher than the rate of
      palliative group (12/17) or transplantation group (17/21), which was also
      statistically significant (P < .01).In our study, we believe in that all stages
      of hepatic alveolar echinococcosis should take active surgical interventions, and
      radical hepatic resection should be considered as the first-choice treatment for
      early stage of alveolar echinococcosis, while palliative surgery is still helpful
      to relieve symptoms and improve the life quality for advanced patients. Liver
      transplantation might also be an alternative option for the late-stage hepatic
      alveolar echinococcosis.

PMID- 29465546
TI  - Bilateral abducens nerve palsies and urinary retention caused by the rupture of a
      vertebral artery aneurysm: A case report and literature review: Erratum.

PMID- 29465545
TI  - Metformin reduces the risk of cancer in patients with type 2 diabetes: An
      analysis based on the Korean National Diabetes Program Cohort.
AB  - The epidemiological literature suggests that insulin resistance,
      hyperinsulinemia, and increased levels of insulin-like growth factors place
      patients with type 2 diabetes mellitus (T2DM) at greater risk of cancer. The
      association between cancer incidence and the use of antidiabetic medications in
      patients with T2DM has been recently examined. There have been conflicting
      reports regarding an association between metformin and cancer risk. The aim of
      this study was to investigate the relationship between metformin use and the
      incidence of cancer in Koreans with T2DM.Data from The Korean National Diabetes
      Program (KNDP, 2006-2014), a nationwide, large-scale, prospective, multicenter
      cohort study in Korea, were used to study patients with T2DM. Patients >=30 years
      old whose complete medical records were available were included in this study.
      Patients with a history of any cancer on KNDP registration or those who had been
      diagnosed with any type of cancer within 1 year of metformin use were excluded.
      Survival curves with respect to the incidence of cancer were plotted using the
      Kaplan-Meier method. Hazard ratios and 95% confidence intervals for cancer were
      estimated in a Cox proportional hazards regression analysis.During a mean 5.8
      years of follow-up, 164 of the 1918 study patients (335 metformin nonusers and
      1583 metformin users) developed cancer. The incidence per 1000 person-years was
      21.8 in metformin nonusers and 13.2 in metformin users. Metformin users had a
      reduced risk of cancer, even after adjustment for demographic characteristics,
      metabolic parameters, diabetic complications, and other antidiabetic medications
      (hazard ratio 0.513, 95% confidence interval 0.318-0.826, P = .0060). Subgroup
      analysis of metformin users showed a reduced risk of cancer in males, patients <
      65 years of age, patients with a T2DM duration < 5 years, nonobese patients,
      nonsmokers, and good glycemic control group.This large-scale, prospective,
      multicenter cohort study demonstrated an association between metformin use and
      reduced cancer risk in patients with T2DM.

PMID- 29465547
TI  - A medium-term follow-up of adult lumbar tuberculosis treating with 3 surgical
      approaches: Erratum.

PMID- 29465548
TI  - Modified trapeziectomy with ligament reconstruction tendon interposition for the
      treatment of advanced thumb carpometacarpal arthritis: A case report: Erratum.

PMID- 29465549
TI  - Cardiorespiratory parameters and glycated hemoglobin of patients with type 2
      diabetes after a rehabilitation program.
AB  - INTRODUCTION: Cardiovascular autonomic dysfunction reflex of the pathophysiology
      of diabetes mellitus (DM) favors an increase in morbidity and mortality related
      to cardiovascular events, and for this reason has been one of the most studied
      clinical entities. METHOD: An experimental study of a randomized clinical trial
      type was therefore proposed to analyze the hemodynamic and glycemic response
      after the practice of a rehabilitation program in patients with type 2 diabetes
      mellitus (T2DM). In this clinical trial the patients will initially be submitted
      to an evaluation protocol that consists of assessing blood pressure, heart rate,
      Borg scale, respiratory rate, oxygen saturation, distance traveled through the 6
      minute walk test, quality of life questionnaire, Pittsburgh sleep quality
      questionnaire, and still glycated hemoglobin and heart rate variability through
      the cardiofrequency meter. After careful evaluation of the patients, they will be
      submitted to a metabolic rehabilitation program composed of aerobic and resisted
      exercises, performed for 12 weeks, in 3 weekly meetings of 60 minutes each. With
      such evaluations, it will be possible to construct with evidence that it is
      possible to work safer metabolic rehabilitation programs in patients with T2DM or
      other diseases that generate cardiovascular risks, guaranteeing them an
      improvement in cardiorespiratory fitness, hemodynamic and glycemic variables,
      allowing improvement of the quality of life. ETHICS AND DISSEMINATION: The
      protocol is approved by the host institution's ethics committee under the number
      1.616.721. Results will be disseminated via peer-reviewed journal articles and
      conferences. This clinical trial is registered at ClinicalTrials.gov identifier:
      NCT3094767.

PMID- 29465550
TI  - Clinical significance of computed tomography-detected ascites in gastric cancer
      patients with peritoneal metastases.
AB  - Patients with peritoneal metastases (PM) are generally considered incurable;
      therefore, the presence of PM is a critical factor in deciding between palliative
      surgery and curative resection as a therapeutic strategy. Previous studies have
      not determined the predictive value of ascites detected on computed tomography
      (CT) for the presence of PM. We aimed to analyze the factors that are associated
      with PM in patients with CT-detected ascites.A total of 2207 consecutive patients
      who were diagnosed with gastric cancer between 2004 and 2013 were identified.
      Eleven patients with liver cirrhosis or chronic renal insufficiency with ascites
      and 57 patients who received previous treatment were excluded. Ninety-eight
      patients who had definite evidence of distant metastasis or PM on CT and 64
      patients who did not undergo surgery were excluded. A total of 91 patients were
      enrolled in the study to analyze the association between CT-detected ascites and
      surgically confirmed PM.Seventy-six patients underwent curative resection and 15
      patients underwent palliative surgery. Twelve patients exhibited peritoneal
      seeding and 37 patients showed regional lymph node metastasis. Regional lymph
      node metastasis, advanced gastric cancer, undifferentiated pathology, and the
      amount of ascites were significantly associated with PM. Multivariable logistic
      regression analysis identified the amount of ascites to be an independent risk
      factor for the presence of PM.Regional lymph node metastasis, advanced gastric
      cancer, undifferentiated pathology, and the amount of ascites were associated
      with PM. The amount of ascites was found to be an independent risk factor for PM.

PMID- 29465551
TI  - Sirolimus alternative to blood transfusion as a life saver in blue rubber bleb
      nevus syndrome: A case report.
AB  - RATIONALE: Blue rubber bleb nevus syndrome (BRBNS) is a rare disease
      characterized by multiple venous malformations. The gastrointestinal bleeding and
      secondary iron deficiency anemia are the most common complications. There are
      currently no effective treatments for BRBNS. Here, we report a case of successful
      treatment with a small dose of sirolimus of a BRBN patient with a de novo gene
      mutation. PATIENT CONCERNS: A 12-year-old female was admitted to our hospital
      with multiple hemangiomas for 12 years. The patient often displayed melena; she
      recently received transfusion of 2 units of red blood cells once every 2 weeks.
      Multiple fist-sized hemangiomas were piled up on both sides and back of the neck,
      and were also noted on the arms, legs, chest, back, and on the tip of the tongue.
      The laboratory findings demonstrated severe anemia. Blood sample sequencing
      detected a heterozygous de novo mutation c.2545C > Tin the TEK gene. DIAGNOSES:
      Based on these findings, final diagnosis of Blue rubber bleb nevus syndrome
      (BRBNS) was made. INTERVENTIONS: After the diagnosis, low-dose sirolimus was
      orally administered. OUTCOMES: The patient's hemoglobin was increased after
      treatment with sirolimus for 1 month. Since the initial treatment with sirolimus,
      she had not received any blood transfusions. The skin and mucosal hemangioma
      decreased significantly, and new digestive tract hemorrhage, muscle hematoma, or
      adverse drug reactions were not observed. LESSONS: we report a case of a mutation
      in exon 15 of the TEK gene leading to BRBN. It was successfully treated with a
      small dose of sirolimus as an alternative to blood transfusion in order to save
      the of BRBN patient's life.

PMID- 29465552
TI  - Diagnostic accuracy of magnetic resonance imaging, transvaginal, and transrectal
      ultrasonography in deep infiltrating endometriosis.
AB  - To determine the diagnostic accuracy of pelvic magnetic resonance imaging (MRI),
      transvaginal sonography (TVS), and transrectal sonography (TRS) in diagnosis of
      deep infiltrating endometriosis (DIE).This diagnostic accuracy study was
      conducted during a 2-year period including a total number of 317 patients with
      signs and symptoms of endometriosis. All the patients were evaluated by pelvic
      MRI, TVS, and TRS in the same center. The criterion standard was considered to be
      the laparoscopy and histopathologic examination.Of 317 patients being included in
      the present study, 252 tested positive for DIE. The sensitivity, specificity,
      positive predictive value, and negative predictive value of TVS was found to be
      83.3%, 46.1%, 85.7%, and 41.6%, respectively. These variables were 80.5%, 18.6%,
      79.3%, and 19.7% for TRS and 90.4%, 66.1%, 91.2%, and 64.1% for MRI,
      respectively. MRI had the highest accuracy (85.4%) when compared to TVS (75.7%)
      and TRS (67.8%). The sensitivity of TRS, TVS, and MRI in uterosacral ligament DIE
      was 82.8%, 70.9%, and 63.6%, respectively. On the contrary, specificity had a
      reverse trend, favoring MRI (93.9%, 92.8%, and 89.8% for TVS and TRS,
      respectively).The results of the present study demonstrated that TVS and TRS have
      appropriate diagnostic accuracy in diagnosis of DIE comparable to MRI.

PMID- 29465553
TI  - Prognostic role of platelet to lymphocyte ratio in pancreatic cancers: A meta
      analysis including 3028 patients.
AB  - BACKGROUND: Platelet to lymphocyte ratio (PLR) was recently reported being
      associated with the prognosis of pancreatic cancer (PC), but the prognostic value
      of PLR in pancreatic cancer remains inconsistent. We conduct a meta-analysis to
      evaluate the prognostic role of PLR in patients with PC. METHODS: PubMed, Embase,
      Cochrane Library, and Web of Science were systematically searched for eligible
      studies which investigated the relationship between PLR and clinical outcome of
      patients with pancreatic cancer. Pooled hazard ratios (HRs) and 95% confidence
      intervals (CIs) were calculated to evaluate the prognostic role of PLR in overall
      survival (OS) and progression-free survival (PFS)/time to progression (TTP).
      RESULTS: A total of 16 studies comprising 3028 patients with PC were enrolled in
      this meta-analysis. Pooled analysis demonstrated that elevated PLR predicted a
      poor OS (HR = 1.22, 95% CI: 1.09-1.36, P < .001). Prognostic role of PLR on OS
      were significant in subgroup of Asians (HR = 1.22, 95% CI: 1.11-1.34, P < .001),
      patients treated with chemotherapy (HR = 1.18, 95% CI: 1.04-1.35, P = .01) and
      mixed methods (HR = 1.29, 95% CI: 1.07-1.57, P = .009), American joint committee
      on cancer (AJCC) stage of III-IV (HR = 1.22, 95% CI: 1.09-1.36, P < .001),
      pathological subtype of pancreatic adenocarcinoma (HR = 1.21, 95% CI: 1.08-1.36,
      P = .001), and cut-off value of PLR >=160 (HR = 1.48, 95% CI: 1.25-1.75, P <
      .001). CONCLUSIONS: An elevated PLR is associated with unfavorable overall
      survival in patients with pancreatic cancer.

PMID- 29465554
TI  - Case report: Purulent transformation of granulocytic sarcoma: An unusual pattern
      of differentiation in acute promyelocytic leukemia.
AB  - RATIONALE: Acute promyelocytic leukemia (APL) is a curable subtype of acute
      myeloid leukemia. APL is currently treated with combination of all-trans retinoic
      acid (ATRA) and arsenic trioxide (ATO) resulting in the induction of apoptosis
      and differentiation of the leukemic cells. Differentiation syndrome (so-called
      ATRA syndrome) is the main life-threatening complication of induction therapy
      with these differentiating agents. PATIENT CONCERNS: Herein, we report the case
      of a 49-year-old woman diagnosed with APL with, concomitantly, a bulky cutaneous
      lesion of 10 cm diameter with a red-to-purple background and a necrotic center,
      localized on her abdomen. DIAGNOSES: After 10 days of treatment, the cutaneous
      lesion became purulent. Fluorescence in situ hybridization (FISH) analysis
      performed on this pus confirmed the presence of malignant features in the
      involved granulocytes proving their origin from the differentiation of leukemic
      APL cells, as all the analyzed nuclei showed 2 promyelocytic leukemia (PML)
      retinoic acid receptor-a (RARA) fusions signals. INTERVENTION: The association by
      ATRA and ATO was continued. OUTCOME: Eventually, the evolution was favorable with
      healing in three weeks. LESSONS: This case report therefore highlights the
      differentiation phenomenon of promyelocytic blasts within promyelocytic sarcoma
      with the ATRA-ATO combination and the efficacy of this drug association in
      resolving both the malignant sarcoma and a secondary local infection.

PMID- 29465555
TI  - Two cases of Dieulafoy lesions of the bronchus with novel comorbid associations
      and endobronchial ablative management.
AB  - RATIONALE: Dieulafoy lesions are aberrantly large submucosal arteries most
      frequently associated with gastrointestinal hemorrhage. They are rarely
      identified in the bronchial submucosa and can cause massive hemoptysis. PATIENT
      CONCERNS: We present three episodes of massive hemoptysis in two patients, the
      first with comorbid Alagille syndrome including multiple cardiac and pulmonary
      vascular abnormalities and the second with thyroid cancer metastatic to the
      mediastinum. DIAGNOSES: All episodes were due to Dieulafoy lesions of the
      bronchus based on bronchoscopic appearance. INTERVENTIONS: Bronchoscopic ablation
      using Nd:YAP laser was attempted both patients. OUTCOMES: Nd:YAP laser
      successfully ablated the Dieulafoy lesion in the first case with long-term relief
      from recurrent hemoptysis. The first episode in the second patient responded to
      bronchial artery embolization; laser ablation of a different Dieulafoy lesion
      responsible for the second episode was unsuccessful but additional bronchial
      artery embolization has provided relief from further episodes. LESSONS:
      Bronchoscopic ablation of Dieulafoy lesions of the bronchus can provide durable
      relief from recurrent symptoms. Clinical and anatomical features should be
      considered carefully before intervention, which should only be attempted by
      experienced operators with appropriate ancillary support available.

PMID- 29465556
TI  - Identification of potential target genes for ankylosing spondylitis treatment.
AB  - This study aimed to identify the potential target genes for the treatment of
      ankylosing spondylitis (AS).Dataset GSE25101 was downloaded from Gene Expression
      Omnibus, including 16 AS and 16 normal control blood samples. Differentially
      expressed genes (DEGs) were identified using unmatched t-test in limma package
      with adjusted P < .05. Gene ontology-biological process (GO-BP) and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using
      multifaceted analysis tool for human transcriptome. Protein-protein interaction
      (PPI) network was constructed using STRING and Cytoscape, and module analysis was
      performed using MCODE plug-in. Webgestal was utilized to predict transcriptional
      factor (TF)-microRNA-target network and Comparative Toxicogenomics Database (CTD)
      was applied to predict chemical-target network.A total of 334 DEGs were
      identified, including 136 upregulated genes and 198 downregulated genes.
      According to STRING, a PPI network was constructed and 1 significant clustered
      module was screen out with score = 6.33. MAPK7 (degree = 11) and NDUFS4 (degree =
      10) were 2 important nodes in PPI network, and both of them were significantly
      enriched in cAMP mediated signaling pathway (P = 2.02E-02). MAPK7 could be
      regulated by NFY. Both MAPK7 and NDUFS4 were 2 potential targets for
      Indomethacin.MAPK7 and NDUFS4 played important roles in the pathogenesis of AS
      via cAMP mediated signaling pathway. Both of them could be targeted by
      Indomethacin.

PMID- 29465557
TI  - Follow-up of blood glucose distribution characteristics in a health examination
      population in Chengdu from 2010 to 2016.
AB  - The worldwide prevalence and incidence of diabetes and obesity are increasing in
      pandemic proportions. Thus, regular health examination is an important way for
      early detection of diabetes and glucose intolerance. The present study aims to
      detect the blood glucose distribution characteristics of the participants in the
      Health Examination Center at West China Hospital, Sichuan University from 2010 to
      2016.A prospective cohort included 9168 Chinese participants, aged 18 years or
      more, who had available information on fasting blood glucose concentrations at
      the start of the study (2010). Examination surveys were conducted every year from
      2010 to 2016. Cases having serum level of fasting blood glucose between 2.2 and
      6.1 mmol/L were considered as normality, while serum level of fasting blood
      glucose < 2.2 or higher than 6.2 mmol/L were considered as abnormality.The
      percentage of participants having normal level of glucose was gradually reduced
      both in males and females from 2010 to 2016, by which the percentage of males
      having normal level of glucose was significantly lower than that in females.
      Moreover, the mean level of glucose was significantly increased from 2010 to 2016
      both in males and females overall, and the mean level of glucose was higher in
      males compared with that in females every year. Furthermore, we showed that the
      level of glucose was gradually increased year by year in each age group, and the
      level of glucose was higher in aged cases compared with the young population.The
      study population in the current study showed higher levels of glucose with ages
      increasing, and males indicated higher expression of glucose than that in
      females. Some preventive action may be adopted early and more attention can be
      paid to this health-examination population.

PMID- 29465558
TI  - Analysis of clinical characteristics and treatment of immunoglobulin G4
      associated cholangitis: A retrospective cohort study of 39 IAC patients.
AB  - Immunoglobulin (Ig)G4-associated cholangitis (IAC) is one of the common organ
      manifestations of IgG4-related systemic disease (ISD). IAC and autoimmune
      pancreatitis (AIP) may mimic sclerosing cholangitis, cholangiocarcinoma, or
      pancreatic carcinoma. Diagnosis is based on a combination of clinical,
      biochemical, radiological, and histological findings.To study the clinical
      presentation of and treatment strategy for IAC, we reviewed clinical, serologic,
      and imaging characteristics, as well as treatment response, in 39 patients with
      IAC. The majority of patients were men (82%). Clinical features on presentation
      included obstructive jaundice in 26 patients (67%) and abdominal pain in 20
      (51%). Positive IgG4 immunostaining was seen in 27 patients. The median serum
      IgG4 level before treatment was 769.4 mg/dL (range, 309.1-1229.7 mg/dL). After
      the steroid therapy, the median serum IgG4 level in 23 patients was 247.0 mg/dL
      (range, 139.0-355.0 mg/dL). Cholangiograms were available in 36 (92%) patients.
      Stenosis of the lower part of the common bile duct was found in 26 of 39
      patients. Stenosis was diffusely distributed in the intra- and extrahepatic bile
      ducts in 14 of 39 patients. Additionally, strictures of the bile duct were
      detected in the hilar hepatic lesions in 27 of 39 patients. AIP was the most
      frequent comorbidity (35/39 in this study) of IAC. Other affected organs included
      eyes (n = 6), salivary glands (sialadenitis, n = 10), lymph nodes (mediastinal
      and axillary, n = 3), kidneys (n = 2), and the retroperitoneum (retroperitoneal
      fibrosis, n = 2).Regarding treatment, 29 patients were treated with steroids, of
      whom one underwent pancreatoduodenectomy, and one underwent
      choledochojejunostomy. Eight patients were treated with biliary stents. The
      remaining 19 patients took prednisolone alone. Eight patients achieved
      spontaneous resolution. Four patients with suspected pancreatic cancer or
      cholangiocarcinoma underwent surgery, including 2 patients who also received
      postoperative steroids. All patients were regularly followed up for 9 to 36
      months. Only 2 patients in the steroids treatment group relapsed to manifest
      obstructive jaundice and high serum IgG4 levels. These 2 patients were treated
      with steroids and biliary stents, resulting in complete remission.We also review
      the diagnostic and therapeutic management and discuss recent pathophysiological
      findings, which might aid in understanding the molecular mechanisms contributing
      to IAC and other manifestations of IgG4-related diseases (IgG4-RD). Biomarkers
      that are more accurate are needed to correctly diagnose IAC and prevent
      misdiagnoses and unnecessary therapeutic interventions.

PMID- 29465559
TI  - Cardiac rehabilitation in acute myocardial infarction patients after percutaneous
      coronary intervention: A community-based study.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is one of the leading causes of
      death and physical disability worldwide. However, the development of community-
      based cardiac rehabilitation (CR) in AMI patients is hysteretic. Here, we aimed
      to evaluate the safety and efficacy of CR applied in the community in AMI
      patients who underwent percutaneous coronary intervention (PCI). METHODS: A total
      of 130 ST-segment elevated myocardial infarction (STEMI) patients after PCI were
      randomly divided into 2 groups in the community, rehabilitation group (n = 65)
      and control group (n = 65). Cardiac function, a 6-minute walk distance, exercise
      time and steps, cardiovascular risk factors were monitored respectively and
      compared before and after the intervention of 2 groups. The software of EpiData
      3.1 was used to input research data and SPSS16.0 was used for statistical
      analysis. RESULTS: After a planned rehabilitation intervention, the
      rehabilitation group showed better results than the control group. The
      rehabilitation group had a significant improvement in recurrence angina and
      readmission (P < .01). Left ventricular ejection fraction (LVEF) of
      rehabilitation group showed improvement in phase II (t = 4.963, P < .01) and
      phase III (t = 11.802, P < .01), and the New York Heart Association (NYHA)
      classification was recovered within class II. There was a significant difference
      compared with before (Z = 7.238, P < .01). Six minutes walking distance, aerobic
      exercise time, and steps all achieved rehabilitation requirements in
      rehabilitation group in phase II and III, there existed distinct variation
      between 2 phases. Rehabilitation group had a better result in cardiovascular risk
      factors than control group (P < .05). CONCLUSION: Community-based CR after PCI
      through simple but safe exercise methods can improve the AMI patient's living
      quality, which includes increasing cardiac ejection fraction, exercise tolerance,
      and physical status. It must be emphasized that the good result should be
      established by the foundation of close cooperation between cardiologists and
      general practitioners, also the importance of cooperation of patients and their
      families should not be ignored. The rehabilitation program we used is feasible,
      safe, and effective.

PMID- 29465560
TI  - Olanzapine and haloperidol for the treatment of acute symptoms of mental
      disorders induced by amphetamine-type stimulants: A randomized controlled trial.
AB  - BACKGROUND: This study aimed to compare olanzapine and haloperidol efficacies in
      the treatment of acute psychiatric symptoms due to amphetamine-type stimulants
      (ATSs). METHODS: The Zelen II design method was used; 124 patients with acute
      mental disorders due to amphetamine were randomly divided into olanzapine group
      (n = 63) and haloperidol group (n = 61). Then, a 4-week open-label medical
      therapy was performed. Clinical Global Impression Scale Item 2 was employed to
      evaluate the onset time; meanwhile, Brief Psychiatric Rating Scale (BPRS) was
      used at baseline and at posttreatment weeks 1, 2, and 4. Moreover, adverse
      reactions during the treatment were recorded. RESULTS: Onset time in the
      olanzapine group was significantly earlier than in the haloperidol group; BPRS
      scores in the olanzapine group were significantly lower than haloperidol group
      values at 1 and 2 weeks of treatment. The overall effective rates had no
      statistically significant difference. CONCLUSION: Short-term olanzapine and
      haloperidol treatments had equivalent efficacies in the treatment of acute
      symptoms of mental disorders due to ATSs; however, olanzapine administration
      resulted in relatively earlier disease onset, with less adverse reactions.

PMID- 29465561
TI  - Cross-sectional study of CD4: CD8 ratio recovery in young adults with perinatally
      acquired HIV-1 infection.
AB  - Antiretroviral therapy (ART) has improved survival into adulthood for young
      people with perinatally acquired HIV-1 (yp-PaHIV), but long-term prognosis
      remains unclear. We hypothesized that on-going immune activation, reflected in
      the failure of CD4:CD8 ratio normalization would be observed in yp-PaHIV, despite
      ART.A cross-sectional study of routinely collected clinical data from a cohort of
      yp-PaHIV (>=16 years).Data were collected from records of individuals attending a
      specialist clinic for yp-PaHIV transitioning to adult care. CD4:CD8 ratio and
      proportion with CD4:CD8 ratio >=1, demographic data and viral parameters,
      including HIV-1 viral load (VL) and human cytomegalovirus (CMV) IgG, were
      analyzed with IBM SPSS Statistics v22.A total of 115 yp-PaHIV, median (IQR) age
      22.0 (20.0-24.0) years, were studied, of whom 59 were females, and the majority
      were Black African 75/115 (65.2%). Where measured, CMV antibodies were frequently
      detected (71/74, 95.9%) and CMV IgG titre was inversely associated with CD4:CD8
      ratio, (Rho -0.383, P = .012). Of those taking ART, 69 out of 90 (76.7%) yp-PaHIV
      had suppressed HIV viremia (<50 RNA copies/mL) and recovery of CD4:CD8 ratio to
      >=1 was seen in 26 out of 69 (37.7%) with suppressed HIV viremia. Persistence of
      low CD4:CD8 ratio was observed even in those with a CD4 count >=500 cells/MUL,
      where 28/52 (53.8%) had a CD4:CD8 ratio <1. Of those with suppressed viremia, the
      median (IQR) age for starting ART was 8.0 (5.0-12.8) years and CD4:CD8 ratio was
      inversely associated with age at ART start, Rho -0.348, (P = .028).In this cohort
      of yp-PaHIV, despite lifelong HIV infection and widespread CMV coinfection,
      CD4:CD8 ratio recovery rate was comparable to adults treated in acute infection.
      Where persistence of CD4:CD8 ratio abnormality was observed, on-going immune
      activation may have significance for non-AIDS outcomes. Taken together our
      findings indicate immune resilience to be a feature of these adult survivors of
      perinatally acquired HIV infection, which can be supported with early
      antiretroviral therapy.

PMID- 29465562
TI  - Subacute onset leukodystrophy and visual-spatial disorders revealing
      phenylketonuria combined with homocysteinmia in adulthood: A case report.
AB  - RATIONALE: Phenylketonuria (PKU) is a metabolic disorder, which manifests a
      progressive irreversible neurological impairment during infancy and childhood.
      Hyperhomocysteinemia also showed that it might be involved in pathophysiology of
      many neuropsychiatric disorders. The late-onset clinical manifestations of these
      2 diseases have not been reported elsewhere. We speculated that the late-onset
      PKU is caused by 2 kinds of metabolic dysfunction synergistically, especially a
      short period of irregular diet directly caused clinical symptoms. PATIENT
      CONCERNS: A 21-year old Asian male patient demonstrated subacute leukodystrophy
      and visual-spatial disorders of late onset in adulthood. DIAGNOSES:
      Phenylketonuria combined with homocysteinmia, who presented with heterozygous
      mutations in gene encoding PAH p.G247R (c.739G>C) and p.Y204C (c.611A>G), along
      with homozygous mutation of gene encoding MTHFR c.677C>T. INTERVENTIONS: The
      patient was treated with cobalamine (500 MUg/day), vitamin B6 (30 mg/day), folate
      (5 mg/day) and encouraged to follow a protein-restricted diet. OUTCOMES: Visual
      disorientation and cognitive function showed improvement. Head MR showed similar
      resolution with the original lesion. Serum homocysteine and folate analysis were
      normal with decreased phenylalanine level. LESSONS: This case suggests that
      neurological involvement of progressive nervous system dysfunction could be
      caused by more than one kind of inherited metabolic disturbances, and each one
      can induce or deteriorate the manifestations of another metabolic disorders.

PMID- 29465563
TI  - Non-Hodgkin lymphoma, diagnostic, and prognostic particularities in children - a
      series of case reports and a review of the literature (CARE compliant).
AB  - RATIONALE: Non-Hodgkin lymphoma remains an unpredictable condition in pediatric
      patients. PATIENT CONCERNS: Our first case describes an 8-year-old boy with a
      history of iron deficiency anemia, admitted in our clinic for recurrent abdominal
      pain, weight loss, loss of appetite, diarrheic stools, and fever. The second case
      also describes an 8-year-old boy admitted for abdominal pain and vomiting. The
      3rd case refers to a 4 years and 10 months old boy admitted in our clinic with
      abdominal pain and loss of appetite, who was initially admitted in the Pediatrics
      Surgery Clinic with the suspicion of appendicitis. Our 4th patient was a 5-year
      old boy admitted in our clinic for abdominal pain and intermittent diarrheic
      stools. DIAGNOSES: In the first case, the laboratory tests showed anemia,
      thrombocytosis, elevated inflammatory biomarkers, a low level of iron, and
      hypoproteinemia. The abdominal ultrasound and CT exam revealed an abdominal mass,
      and the histopathological exam established the diagnosis of diffuse large B-cell
      lymphoma of the bowel. In the second case, the laboratory tests pointed out
      anemia, elevated ESR and lactate dehydrogenase level, while both abdominal
      ultrasound and CT exams showed an abdominal mass. The histopathological exam
      confirmed the diagnosis of Burkitt lymphoma. Regarding our 3rd case, the
      laboratory findings revealed leukocytosis, anemia, thrombocytosis, increased
      inflammatory biomarkers, elevated LDH, and a low level of iron. The abdominal
      ultrasound and the CT scan revealed an abdominal mass which, according to the
      histopathological exam, was a Burkitt lymphoma. Due to the cranial CT findings
      the patient was diagnosed with IV stage Burkitt lymphoma with central nervous
      system metastases. In our 4th patients we found leukocytosis, anemia, mildly
      increased inflammatory biomarkers, a high level of LDH, hypoproteinemia, and a
      low level of serum Ir. Both ultrasound and abdominal CT exams were negative, but
      the exploratory laparotomy identified an abdominal mass, and according to the
      histopathological exam the patient was diagnosed with Burkitt lymphoma.
      INTERVENTIONS: All the patients followed chemotherapy (B-NHL BFM 04 protocol) and
      supportive treatment. OUTCOMES: The first patient died approximately 4 months
      after the completion of chemotherapy due to tumor relapse, the second patient
      died after the first cure of chemotherapy and the fourth patient died at
      approximately 2 years after the diagnosis. The third patient is recurrence-free
      after 2 years. LESSONS: Despite the advances in the management, NHL remains a
      fatal condition in pediatrics.

PMID- 29465564
TI  - Dental caries and vitamin D3 in children with growth hormone deficiency: A STROBE
      compliant study.
AB  - Vitamin D may prevent dental caries. To date, no attempts have been made to
      examine the correlation between the incidence of caries and the concentrations of
      vitamin D in children with pituitary growth hormone deficiency.The study observed
      patients of the Department of Endocrinology and Diabetology of the University
      Paediatric Hospital of the Medical University of Lublin treated with human
      recombinant growth hormone for pituitary growth hormone deficiency (GHD). The
      study was conducted between October 2014 and June 2015. The study group consisted
      of 121 children and adolescents (6-17 years old), including 56 children from
      rural areas and 65 children from urban areas. The study group was stratified by
      area of residence.In our study, the increase in vitamin D3 [25(OH)D] levels
      reduced the D component by 0.66 per each 10 ng/mL of vitamin D3 concentration.
      The percentage of children with active caries in rural areas is 91.07% (n = 51),
      which is significantly higher than the percentage of children with active caries
      in urban areas (81.54%, n = 53).To date, information regarding the potential
      possibility of reducing the incidence of dental caries by means of increasing the
      levels of vitamin D was sidelined by paediatricians and dentists alike.
      Therefore, this aspect of caries prevention should be highlighted.

PMID- 29465565
TI  - Peripheral whole blood lncRNA expression analysis in patients with eosinophilic
      asthma.
AB  - Long noncoding RNA (lncRNA) plays roles in many diseases including asthma.
      Several lncRNAs function in the early differentiation of T-helper cells. lncRNA
      controls gene transcription, protein expression, and epigenetic regulation. Of
      the 4 asthma phenotypes, eosinophilic asthma (EA) is the most common. However,
      the lncRNAs associated with eosinophilic asthma have yet to be identified.We
      designed a study to identify the circulating lncRNA signature in EA samples. We
      tested whether significant differences in lncRNA expression were observed between
      blood samples from patients with EA and healthy individuals (control). Gene
      ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses
      were performed for the lncRNA-mRNA (messenger RNA) co-expression network. lncRNA
      expression was measured using quantitative real-time PCR (polymerase chain
      reaction).A total of 41 dysregulated lncRNAs and 762 dysregulated mRNAs
      (difference >= 2-fold) were found in EA compared to control samples. GO terms and
      KEGG pathway annotation data revealed that several lncRNAs are significantly
      associated with EA. KEGG pathway annotation indicated that the pathways most
      enriched in EA were measles, T cell receptor signaling pathway, peroxisome
      proliferator activated-receptors (PPAR) signaling pathway, Fc gamma R-mediated
      phagocytosis, NF (nuclear factor) kappa B signaling pathway, chemokine signaling
      pathway, and primary immunodeficiency. Using qRT-PCR, lncRNA was confirmed to
      differ significantly between EA and control samples.The results presented here
      show that several lncRNAs may take part in the immune regulation of EA. Whether
      these lncRNAs can be used as biomarkers needs further study.

PMID- 29465566
TI  - Acupuncture for adults with overactive bladder: A systematic review and meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Overactive bladder is stated as the occurrence of urinary urgency
      which will cause negative impacts and decrease patients' health-related quality
      of life. The aim of this systematic review is to assess the efficiency and safety
      of acupuncture for adults with overactive bladder (OAB) comparing with sham
      acupuncture, drugs, and acupuncture plus drugs. METHODS: We independently
      searched 9 databases from beginning to August 15, 2017. Two writers extracted
      data at the same time independently. Study outcomes were calculated by
      standardized mean differences (SMD) with 95% confidence intervals (CIs) and mean
      difference (MD) with 95% CIs. RESULTS: Ten randomized controlled trials (RCTs)
      with 794 patients were included in this systematic review. The combined results
      showed that electroacupuncture (EA) may be more effective than sham
      electroacupuncture (sham EA) in improving the 24-hour nocturia episodes and EA
      may enhance tolterodine for relieving voiding symptoms and enhancing patients'
      quality of life. However, more trials with high quality and larger sample sizes
      will be needed in the future to provide sufficient evidence. Only 15 of 794 OAB
      patients from the included studies reported mild adverse reactions related to EA,
      therefore, acupuncture is safe for treating OAB. CONCLUSION: Acupuncture might
      have effect in decreasing the number of micturition episodes, incontinence
      episodes, and nocturia episodes. However, the evidence is insufficient to show
      the effect using acupuncture alone or the additional effect to drugs in treating
      OAB.

PMID- 29465567
TI  - Measurement of the nerve root of the lower lumbar region using digital images.
AB  - The purpose of this study was to evaluate the relationship between the nerve root
      of lower lumbar and the surrounding structures using three-dimensional computed
      tomography (3D CT).Twenty-three consecutive patients with thoracolumbar fractures
      without obvious radiological degeneration were retrospectively studied at the
      spinal surgery department of the hospital. The parameters of the relationship
      between the nerve root of the lower lumbar and the surrounding structures were
      measured using 3D CT in the work station of the picture archiving and
      communication system.The size of the dorsal root ganglion (DRG) of the L4 was 5.5
      +/- 0.4 mm on the right side and 5.8 +/- 0.3 mm on the left side. The size of the
      DRG of the L5 was 6.1 +/- 0.5 mm on the right side and 5.7 +/- 0.4 mm on the left
      side. The value of the preganglionic nerve root of the L4 was 11.2 +/- 0.6 mm on
      the right side and 12.3 +/- 0.8 mm on the left side, and the value of the
      preganglionic nerve root of the L5 was 15.1 +/- 1.1 mm on the right side and 14.9
      +/- 0.9 mm on the left side.Using 3D CT imaging constructed in the picture
      archiving and communication system is a practical and convenient method for
      evaluating the relationship between the nerve root and the surrounding structures
      in the routine clinical work of a spinal surgeon. The data obtained through 3D CT
      imaging will be helpful for surgeons, allowing them to become more familiar with
      correlating anatomical knowledge of individual patient.

PMID- 29465568
TI  - Preliminary evidence: the stress-reducing effect of listening to water sounds
      depends on somatic complaints: A randomized trial.
AB  - BACKGROUND: Listening to natural sounds is applied in health contexts in order to
      induce relaxation. However, it remains unclear whether this effect is equally
      efficacious in all individuals or whether it depends on interindividual
      differences. Given that individuals differ in how they are impaired by somatic
      complaints, we investigated whether somatic complaints moderate the stress
      reducing effect of listening to water sounds. METHODS: Sixty healthy women (Mage
      = 25 years) were randomly allocated to 3 different conditions (listening to water
      sounds, a relaxing piece of music, or no auditory stimulus: n = 20 per condition)
      for 10 minutes before they were exposed to a standardized psychosocial stress
      task. Salivary cortisol was assessed before, during, and after the stress task.
      For binary logistic regression analyses, participants were divided into 2 groups:
      1 group with a high salivary cortisol release and 1 group with low cortisol
      release. The Freiburg Complaints Inventory was used to assess occurrence of
      somatic complaints. RESULTS: A significant moderating effect of somatic
      complaints on cortisol secretion was found in the group listening to water sounds
      (chi(1) = 5.87, P < .015) but not in the other 2 groups, explaining 35.7% of the
      variance and correctly classifying 78.9% of the cases. CONCLUSION: The stress
      reducing effect of listening to water sounds appears to depend on the occurrence
      of somatic complaints. This effect was not found in the music or silence
      condition. Individuals with somatic complaints may benefit from other,
      potentially more powerful forms of stress-reducing interventions, that is,
      combinations of visual and auditory stimuli. TRIAL REGISTRATION: not applicable
      (pilot study).

PMID- 29465569
TI  - Three cases of a torn haptic after scleral fixation using a hydrophobic acrylic
      intraocular lens: Case reports.
AB  - RATIONALE: We report 3 cases of a torn haptic after successful scleral fixation
      with a hydrophobic acrylic intraocular lens. PATIENT CONCERNS: Patients
      complained of decreased visual acuity about 1 week to 1 month after scleral
      fixation. DIAGNOSES: In all 3 cases, the direction of the damaged haptic
      correlated with the direction of the pulling force made by the hung suture
      material. Observation of a cheese-wiring effect on scanning electron microscopy
      suggested that the haptic was cut by the suture. INTERVENTIONS: Patients
      underwent re-scleral fixation with caution. OUCTOMES: There was no complication
      of broken haptic after re-scleral fixation. LESSONS: To avoid unexpected haptic
      tears, great caution is needed; surgeons should avoid applying excessive pulling
      force to the intraocular lens when performing scleral fixation using a
      hydrophobic acrylic intraocular lens.

PMID- 29465570
TI  - Transmissibility and familiality of NEO personality dimensions in a sample of
      Korean families with schizophrenia.
AB  - Categorical syndromes such as schizophrenia may represent complexes of many
      continuous psychological structural phenotypes along several dimensions of
      personality development/degeneration. The present study investigated the
      heritability and familiality of Neuroticism-Extraversion-Openness to experience
      (NEO) personality dimensions in Korean families with schizophrenic linkage
      disequilibrium (LD).We have recruited 204 probands (with schizophrenia) with
      their parents and siblings whenever possible. We have used NEO questionnaires for
      measuring personality and symptomatic dimensions. Heritabilities of personality
      dimensions in total 543 family members were estimated using Sequential Oligogenic
      Linkage Analysis Routines (SOLAR). Personality dimensions in total family members
      were compared with those in 307 healthy unrelated controls for measuring the
      familialities using ANOVA analysis.Four of the 5 NEO variables were significantly
      heritable and were included in the subsequent analyses. The 3 groups (control,
      unaffected first-degree relative, case) were found to be significantly different
      and with the expected order of average group scores for all heritable
      dimensions.Our results show that the aberrations in several personality
      dimensions could form the complexity of schizophrenic syndrome as a result of
      genetic-environment coactions or interactions in spite of some limitations
      (recruited family, phenotyping).

PMID- 29465571
TI  - Caspase-1-dependent pyroptosis of peripheral blood mononuclear cells predicts the
      development of sepsis in severe trauma patients: A prospective observational
      study.
AB  - Pyroptosis plays a pivotal role in sepsis and septic shock in animal studies.
      However, its clinical significance in pathological conditions has not been well
      elucidated. This study aimed to evaluate the correlation between the percentage
      of pyroptotic peripheral blood mononuclear cells (PBMCs) and the clinical index
      and to investigate the relationship between PBMCs pyroptosis and the development
      of sepsis in trauma patients.This prospective study was conducted from October
      2016 to May 2017 in a comprehensive trauma center. Sixty trauma patients and 10
      healthy controls were enrolled. Peripheral blood samples were collected from the
      patients within 24 hours after injury. The percentages of pyroptotic and
      apoptotic PBMCs were measured using flow cytometry, and plasma levels of
      cytokines were evaluated using flow cytometric analysis with a human inflammation
      13-plex panel.Trauma patients who developed sepsis had higher percentages of
      pyroptotic and apoptotic PBMCs at admission. Patients who developed sepsis (n =
      33) had higher interleukin (IL)-6, IL-18, and monocyte chemotactic protein-1 (MCP
      1) concentrations at admission than patients (n = 27) who did not develop sepsis.
      The percentage of PBMCs pyroptosis was significantly correlated with injury
      severity score (ISS), acute physiology and chronic health evaluation (APACHE) II
      score, IL-10, IL-18, and MCP-1 levels in trauma patients. PBMCs pyroptosis is a
      better biomarker in predicting the development of sepsis after trauma.This study
      indicates that the percentage of pyroptotic PBMCs increases during the early
      phase of trauma and that this increase is significantly correlated with the
      severity and state of inflammation in trauma patients. PBMCs pyroptosis is a
      potential marker for predicting the development of sepsis after trauma.

PMID- 29465572
TI  - Therapeutic effect of photodynamic therapy for nonresectable cholangiocarcinoma:
      Protocol for a meta-analysis and systematic review.
AB  - BACKGROUND: Cholangiocarcinoma is a malignant neoplasia that originates in the
      bile ducts. Most patients with cholangiocarcinoma are inoperable at the time of
      diagnosis. photodynamic therapy (PDT) is a fairly well accepted treatment in
      clinical practice for nonresectable cholangiocarcinoma (NCC) but lack of
      quantitatively assessment. Herein, we present a protocol for a systematic review
      to identify the efficacy of PDT in patients with NCC. METHODS: We will search
      PUBMED, SpringerLink, Cochrane Library, the Chinese Biomedical database (CBM),
      WanFang data, China National Knowledge Infrastructure (CNKI) up to December 2017.
      Studies will be screened by title, abstract, and full text independently and in
      duplicate. Studies that report PDT in patients with nonresectable
      cholangiocarcinoma will be eligible for inclusion. Outcome variables will be
      assessed included survival benefit, health status and quality of life, and
      adverse events with photodynamic therapy. Assessment of risk of bias and data
      synthesis will be performed using Revman software. The hazard ratios will be
      extracted from the survival curves using Tierney Method. Heterogeneity among
      studies will be assessed using the I statistic. RESULTS: This study will review
      randomized controlled trials, cohort studies, or retrospective studies and
      quantitatively assess the efficacy of PDT in patients with NCC for the latest
      evidence-based recommendation. CONCLUSION: This study will evaluate therapeutic
      effect of PDT in patients with NCC systematically. We expect that the results
      from this systematic review for clinical trials will help inform clinical
      practice in NCC.

PMID- 29465573
TI  - Synovium as a widespread pathway to the adjacent joint in undifferentiated high
      grade pleomorphic sarcoma of the tibia: A case report.
AB  - RATIONALE: Undifferentiated high-grade pleomorphic sarcoma (UPS), originated from
      bone, is a rare tumor, accounting for 2% to 5% of all primary maligment bone
      neoplasms. Skip lesion can be found in undifferentiated high-grade pleomorphic
      sarcoma of bone (UPS-B). However, the direct invasion across the articular
      synovium to bone has not been reported previously. PATIENT CONCERNS: We report an
      unusual case of a 65-year-old man complained of a year history of pain, swelling,
      and limitation of activity in the left knee joint. At the proximal tibia, there
      was extensive invasion of articular synovium, which provides a direct anatomic
      pathway for the tumor invasion to the adjacent bone, including patella and
      femoral condyle. DIAGNOSES: Magnetic resonance imaging was important in defining
      the marrow involvement and joint invasion, including the thickening articular
      synovium. Subsequent pathological examination confirmed the diagnosis of UPS.
      INTERVENTIONS: The patient underwent an extensive resection of the knee joint,
      except for the patellar. OUTCOMES: After operation, routine chemotherapy was
      performed. Unfortunately, half a year later, soft tissue swelling of whole thigh
      was found. Then this patient came our hospital again. Positron emission
      tomography imaging showed there was recurrence of UPS with lung metastasis. A
      week later, this patient died. LESSONS: In contrast to frequent infiltration
      pathway, the articular synovium as a media for this tumor spread is rare. This
      study adds a better understanding of this direct invasion way to the medical
      literature.

PMID- 29465574
TI  - Simultaneous acute Marchiafava-Bignami disease and central pontine myelinolysis:
      A case report of a challenging diagnosis.
AB  - RATIONALE: Marchiafava-Bignami disease (MBD) is a rare disease characterized by
      demyelination of the corpus callosum. It is most commonly seen in patients with
      chronic alcoholism. The clinical diagnosis of MBD can be difficult due to its
      nonspecific manifestation. Central pontine myelinolysis (CPM) occurs mostly as a
      complication of severe and prolonged hyponatremia, especially when corrected too
      rapidly. However, CPM can be associated with chronic alcoholism and its clinical
      presentation can be heterogeneous. Because both MBD and CPM can have fatal
      outcomes, early recognition and treatment can result in a better prognosis. We
      present a very rare case of simultaneous acute Marchiafava-Bignami disease and
      central pontine myelinolysis in a patient with chronic alcoholism who was
      diagnosed unexpectedly using brain magnetic resonance imaging and improved after
      proper treatment. PATIENT CONCERNS: We presented a case of a 39-year-old patient
      who visited the hospital with general weakness and an altered neurologic
      condition after a week of vomiting. DIAGNOSIS: The patient was diagnosed with
      simultaneous acute Marchiafava-Bignami disease and central pontine myelinolysis
      using brain magnetic resonance imaging. INTERVENTION: Administration of a high
      dose of thiamine. OUTCOMES: The neurologic signs improved after a week of
      thiamine administration. LESSONS: This case suggests that Marchiafava-Bignami
      disease and central pontine myelinolysis might have a common pathogenesis, and
      brain magnetic resonance imaging is of crucial importance in chronic alcoholic
      patients presenting with nonspecific neurological deterioration. The appropriate
      administration of thiamine may prevent poor outcomes.

PMID- 29465575
TI  - Impact of vitamin D receptor and binding protein gene polymorphisms in clinical
      and laboratory data of HCV patients: Cross sectional study.
AB  - Potential relationship of vitamin D, vitamin D receptor (VDR), and vitamin D
      binding protein (DBP) have been suggested in the pathophysiology of hepatitis C
      virus (HCV) infection. The aim of this observational study is to determine
      vitamin D levels, and VDR and DBP genetic polymorphism according demographic and
      laboratory data in chronic HCV patients (CHC).A total of 148 CHC patients gave
      serum samples for testing 25-hydroxyvitamin D (25 (OH)D) level by
      immunochemiluminometric assay (<20 ng/mL defined as deficient) and donated blood
      samples to allelic discrimination analysis using TaqMan assays. Analyzed single
      nucleotide polymorphisms (SNPs) were: VDR-rs7975232 (ApaI) C>A, rs731236 A>G
      (TaqI), rs1544410 C>T (BsmI), rs10735810 T>C (FokI) and carrier globulin/binding
      protein (GC)-rs4588 and rs7041 and the haplotype bAt [CCA]. Hepatic fibrosis was
      assessed using Fib-4 and Forns index.Eighty-two (54.40%) patients demonstrated
      deficiency of vitamin D and this was associated to AST (P = .019 [CI: 1.003
      1.034]), total cholesterol (P = .038 [CI: 1.004-1.164]), fibrosis grade (P < .001
      [CI: 0.000-0.844]), and FokI (P = .028) allele T presence. Association was found
      between VDR polymorphism and fibrosis (BsmI andTaqI), triglycerides (TaqI), and
      HDL (FokI). DBP polymorphism was associated to HCV genotype (GC rs7041), previous
      HCV treatment, and GGT (GC rs4588).In conclusion, low frequency of vitamin D
      deficiency was found, but VDR polymorphisms were frequently associated to
      fibrosis grade suggesting that they could be used as disease evaluation markers
      to understand the mechanisms underlying the virus-host interaction.

PMID- 29465576
TI  - Delayed epidural pseudoaneurysm following cervical laminectomy and
      instrumentation in a patient with canal stenosis secondary to skeletal fluorosis:
      A case report.
AB  - RATIONALE: The typical intraoperative presentation of vertebral artery injury
      (VAI) usually involves profuse bleeding and requires immediate treatment.
      However, an occult VAI may occur intraoperatively and result in delayed life
      threatening epidural pseudoaneurysm several days postoperatively. PATIENT
      CONCERNS: A 21-year-old man with compressive cervical myelopathy resulting from
      canal stenosis of skeletal fluorosis underwent decompression of C1 to C7 and
      instrumentation from C2 to C7. No impressive bleeding event occurred during the
      operation. On postoperative day 40, progressive quadriplegia developed.
      DIAGNOSES: Pseudoaneurysm of the VA was established by angiography.
      INTERVENTIONS: After occlusion of the right VA, the patient underwent hematoma
      clearing. OUTCOMES: Fortunately, the patient experienced significant recovery of
      neurologic function after the second surgery. LESSONS: From this case, we realize
      even in the absence of obvious signs of VAI during a cervical operation,
      postoperative evaluation should be mandatory for suspected bleeding events
      occurring at VAI-prone sites during surgery. Moreover, the bone morphological
      abnormality of skeletal fluorosis was determined to be the most important risk
      contributing to VAI in this case. The safety limits of bone removal should be
      determined preoperatively to avoid the effects of bone morphological
      abnormalities.

PMID- 29465577
TI  - Nitrite-induced acute kidney injury with secondary hyperparathyroidism: Case
      report and literature review.
AB  - RATIONALE: Acute kidney injury (AKI) with hyperparathyroidism caused by nitrite
      was rare, and renal function and parathyroid hormone (PTH) decreased to normal
      range after therapy. PATIENT CONCERNS: Acute kidney injury was diagnosed in a 40
      year-old male with hyperparathyroidism and cyanosis of his hands and both
      forearms. DIAGNOSES: The patient ate some recently pickled vegetables, and he
      experienced nausea, vomiting and diarrhoea without oliguria or anuria;
      Additionally, his hands and both forearms had a typical blue ash appearance.
      After admission, the laboratory findings indicated theincreasing serum creatinine
      (Scr) and parathyroid hormone (PTH). He was diagnosed as acute kidney injury with
      hyperparathyroidism caused by nitrite. INTERVENTIONS: The patient stopped eating
      the pickled vegetables and was given rehydration, added calories and other
      supportive therapy without any glucocorticoids. OUTCOMES: According to his
      clinical manifestations, laboratory findings and imaging results, the patient was
      diagnosed with acute kidney injury with secondary hyperparathyroidism. He was
      given symptomatic supportive care therapy. After one week, the serum creatinine,
      parathyroid hormone (PTH), hypercalcemia, hyperphosphatemia, proteinuria, and
      urine red blood cell values decreased to normal range. LESSONS: Nitrite-induced
      acute kidney injury with secondary hyperparathyroidism was relatively rare. After
      therapy, the function of the kidney and parathyroid returned to normal. This case
      suggests that detailed collection of medical history, physical examination and
      correct symptomatic treatment is very important.

PMID- 29465578
TI  - Short tandem repeat analysis for confirmation of uterine non-gestational
      choriocarcinoma in a postmenopausal Taiwanese woman.
AB  - RATIONALE: Rare uterine choriocarcinoma can be differentiated gestational from
      nongestational choriocarcinoma by using short tandem repeats (STRs). PATIENT
      CONCERNS: A 56-year-old Taiwanese woman underwent staging surgery because of
      suspicion of high-grade endometrial cancer. The pathology-confirmed uterine tumor
      with syncytiotrophoblasts and decidual change of the endometrium was harvested.
      DIAGNOSIS: Uterine nongestational choriocarcinoma. INTERVENTIONS: The tumor
      specimen, the patient's blood, and her husband's blood were drawn for STRs
      analysis using polymerase chain reaction amplification kit. The genotype of the
      tumor cells was solely maternal and made the diagnosis of uterine nongestational
      choriocarcinoma. OUTCOME: Adjuvant chemotherapy with etoposide, methotrexate,
      actinomycin D, cyclophosphamide, vincristine regimen achieved good response in
      the patient. The patient is now recurrence-free for 12 months. LESSONS: STRs aid
      precise classification of rare choriocarcinoma. We encourage using the method to
      analyze suspicious choriocarcinoma.

PMID- 29465579
TI  - Efficacy of alemtuzumab and natalizumab in the treatment of different stages of
      multiple sclerosis patients.
AB  - BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease, in which the
      insulating covers of nerve cells in the brain and spinal cord are demyelinated.
      This study was conducted to compare the efficacy of alemtuzumab and natalizumab
      in the treatment of different stages of MS patients. METHODS: A total of 585
      patients diagnosed with MS and hospitalized were included and analyzed after
      which they were divided into the primary progressive MS A and B groups, the
      relapsing-remitting MS (RRMS) C and D groups, and the secondary progressive MS E
      and F groups. Patients in A, C, and E groups were administered alemtuzumab while
      those in B, D, and F groups were administered natalizumab for the treatment. The
      expanded disability status scale (EDSS) scores and the EDSS difference were
      calculated before and after treatment. The number of head magnetic resonance
      imaging enhanced lesions in the patients, recurrence time and recurrence rate
      were measured before and after treatment. RESULTS: The EDSS score of the RRMS
      group was significantly lower than that of the primary progressive MS group and
      the secondary progressive MS group. After 12 months of treatment, the EDSS score
      of RRMS patients treated with natalizumab was significantly lower compared with
      the patients with alemtuzumab, and the difference before and after treatment was
      significantly higher than alemtuzumab. The recurrence rate of the RRMS-D group
      was significantly lower than the RRMS-C group. After 12 months of treatment,
      compared with the RRMS-C group, a significant reduction was observed in the
      number of head magnetic resonance imaging enhanced lesions and longer recurrence
      time in the RRMS-D group. CONCLUSION: The efficacy of natalizumab was better than
      alemtuzumab in the treatment of patients in the RRMS group, while there was no
      significant difference among other stages of MS patients, which provided the
      theoretical basis and clinical guidance for the treatment of different stages of
      MS.

PMID- 29465580
TI  - Standard values for gas-perfusion manometry of the esophagus.
AB  - The manometry with water-perfused or solid-state catheters is the predominant
      diagnostic procedure to detect motility disorders of the esophagus. Another
      method is the manometry using gas-perfused catheters. Although the high
      resolution manometry is the method of first choice, the conventional manometry
      with helium has some advantages: the simple and hygienically unproblematic use
      and the absence of any artefacts by the perfusion medium compared with water
      perfusion, and the considerably lower costs compared with the solid-state
      catheters. Every method has own normal values because of the specific pressure
      transmission and the design of the catheter probes. To our knowledge, normal
      values for gas-perfusion manometry of the esophagus have not yet been
      published.The esophageal manometry with helium-perfused catheters was performed
      in 30 healthy volunteers. The main parameters of the esophageal motility and the
      lower esophageal sphincter were analyzed by liquid and bolus-like swallows and
      compared with the previous published values in other manometric procedures.The
      values of the motility in the distal esophagus are consistent; the pressure of
      the lower esophageal sphincter is generally lower than with other methods. The
      distal wave amplitude and the propagation velocity are significant higher in the
      distal esophagus than in the middle. The perfusion medium is well tolerated by
      the investigated volunteers.

PMID- 29465581
TI  - Atypical microdeletion in 22q11 deletion syndrome reveals new candidate causative
      genes: A case report and literature review.
AB  - RATIONALE: 22q11 deletion syndrome, the most common chromosomal microdeletion
      disease, is caused by megabase-sized deletions on chromosome 22q11.2. It is
      characterized by a wide spectrum of congenital anomalies in velopharyngeal and
      facial, cardiac, genitourinary, vertebroskeletal, respiratory, digestive, and
      central nervous systems. Phenotype-genotype studies have revealed several
      causative genes that regulate the development of the third and fourth pharyngeal
      arches in human. However, the exact pathogenesis of this syndrome remains
      unknown. Herein, we report a case of 22q11 deletion syndrome with an atypical
      microdeletion of 125 kb. PATIENT CONCERNS: A 15-year-old Chinese girl presented
      with symptoms of facial dysmorphia, cardiac defects, velopharyngeal
      insufficiency, splenomegaly, immunodeficiency, and thrombocytopenia. DIAGNOSES:
      Microarray analysis revealed a 22q11.23 deletion of 125 kb (chromosome 22:
      24276973-24402263), suggesting the diagnosis of 22q11 deletion syndrome. The
      haploinsufficient genes included GSTT2B, GSTT2, DDTL, DDT, GSTTP1, LOC391322,
      GSTT1, and GSTTP2. INTERVENTIONS: The patient was administrated glucocorticoids
      and calcium supplements. OUTCOMES: No epistaxis or petechiae episode occurred
      during the follow-up; her platelet count ranged between 60 * 10 and 80 * 10/L.
      LESSONS: Although none of the previous reported causative genes were affected in
      the patient, her clinical manifestations were typical of 22q11 deletion syndrome,
      apart from her progressive splenomegaly. This case indicated 8 new candidate
      pathogenic genes for 22q11 deletion syndrome. Given that the loss of these genes
      was sufficient to induce 22q11DS defects, whether these genes directly influence
      the pathogenesis of 22q11DS or through interactions with known hotspot mutations
      is worthy of research.

PMID- 29465582
TI  - Successfully treating hand primary tuberculous synovitis by synovectomy combined
      antituberculous therapy: A case report.
AB  - RATIONALE: Primary tuberculous infection in hand and wrist is a rare disease. Few
      articles reported on hand primary tuberculous synovitis. PATIENT CONCERNS: A 68
      year-old Chinese male, without history of tuberculosis (TB), had complained of
      pain and swelling in right palm and little finger for 3 months. Patient came to
      our hospital on 9th Oct 2016. X-ray just showed soft tissue swelling in little
      finger. Magnetic resonance imaging (MRI) showed synovitis around flexor tendon of
      little finger, volar palm, and carpal tunnel. Notably, it also implied nodular
      images in little finger sizing 5 mm * 11 mm. Laboratory tests revealed C-reactive
      protein (CRP): 22 mg/L, erythrocyte sedimentation rate (ESR): 49 mm/h, and white
      blood cells (WBC): 11.8 * 10/L. DIAGNOSES: He was diagnosed with primary hand
      tuberculous synovitis. INTERVENTIONS: The patient received aspiration biopsy in
      right palm guided by ultrasound on 13rd Oct and pathological examination
      indicated Mycobacterium tuberculosis (MTB) infection. We performed radical
      synovetomy and collected abnormal tissue for pathological examination on 18th
      Oct. Finally, result showed MTB infection, which was the same with the result of
      first pathological examination. Then, this patient received antituberculous
      treatment. OUTCOMES: One year after operation, pain and swelling relieve and no
      recurrence of the clinical symptoms happened. LESSONS: Primary tuberculous
      synovitis of hand and wrist is rare, MTB infection should be considered as an
      infectious agent, especially in developing countries. Radical synovectomy and
      antituberculous treatment regain a satisfactory outcome.

PMID- 29465584
TI  - Duplication of the extrahepatic bile duct: A case report and review of the
      literatures.
AB  - RATIONALE: Duplication of the extrahepatic bile duct is an extremely rare
      congenital anomaly of the biliary system. PATIENT CONCERNS: A 44-year-old woman
      presented with a history of continuous upper abdominal pain and vomiting.
      DIAGNOSES: Magnetic resonance cholangiopancreatography (MRCP) disclosed diffuse
      dilatation of the intrahepatic and extrahepatic bile ducts. Endoscopic retrograde
      cholangiopancreatography (ERCP) showed the presence of two extrahepatic bile
      ducts with calculus at the distal end of the CBD. INTERVENTIONS: Laparoscopic
      cholecystectomy (LC) was performed after an ERCP. Choledochoscopy, performed
      during the operation, showed duplicated common bile duct and the cystic duct was
      seen opening at the right side of the extrahepatic duct. OUTCOMES: The patient
      was doing well after 6 months of follow-up. LESSONS: We reported a case of a
      double common duct with choledocholithiasis and gallstone. This rare anomaly may
      lead to cholangitis, common bile duct injury during surgery, malignancy
      occurrence, and should be treated with extreme care.

PMID- 29465583
TI  - "Living High-Training Low" improved weight loss and glucagon-like peptide-1 level
      in a 4-week weight loss program in adolescents with obesity: A pilot study.
AB  - BACKGROUND: "Living High-Training Low" (LHTL) is effective for the improvement of
      athletic ability; however, little is known about the effect of LHTL on obese
      individuals. The present study determined whether LHTL would have favorable
      influence on body composition, rebalance the appetite hormones, and explore the
      underlying mechanism. METHODS: Adolescents with obesity [body mass index (BMI)
      >30 kg/m] were randomly assigned to "Living Low-Training Low" (LLTL, n = 19)
      group that slept in a normobaric normoxia condition and the LHTL (n = 16) group
      slept in a normobaric hypoxia room (14.7% PO2 ~2700 m). Both groups underwent the
      same aerobic exercise training program. Morphological, blood lipids, and appetite
      hormones were measured and assessed. RESULTS: After the intervention, the body
      composition improved in both groups, whereas reductions in body weight (BW), BMI,
      and lean body mass increased significantly in the LHTL group (all, P < .05). In
      the LLTL group, cholecystokinin (CCK) decreased remarkably (P < .05) and CCK
      changes were positively associated with changes in BW (r = 0.585, P = .011) and
      BMI (r = 0.587, P = .010). However, in the LHTL group, changes in plasma glucagon
      like peptide-1 (GLP-1) and interleukin-6 (IL-6) levels, positively correlated
      with each other (r = 0.708, P = .015) but negatively with BW changes (r = -0.608,
      P = .027 and r = -0.518, P = .048, respectively). CONCLUSION: The results
      indicated that LHTL could induce more weight loss safely and efficiently as
      compared to LLTL and increase the plasma GLP-1 levels that may be mediated by IL
      6 to rebalance the appetite. Thus, an efficient method to treat obesity and
      prevent weight regain by appetite rebalance in hypoxia condition was established.

PMID- 29465585
TI  - Occurrence of signet-ring cell carcinoma with cholangiocarcinoma 25 years after
      choledochal cyst excision: A case report.
AB  - RATIONALE: Choledochal cysts are a risk factor for the development of
      cholangiocarcinoma. Hence, complete surgical excision is the preferred treatment
      in most cases. However, cholangiocarcinoma still can develop from the remnant
      biliary system after surgical excision. Signet-ring cell carcinoma is a rare type
      of cancer of the biliary system, and the occurrence of signet-ring cell carcinoma
      after surgical excision of choledochal cysts has not been reported in the English
      literature to date. PATIENT CONCERNS: We report a case of a 32-year-old woman who
      presented with a 1-month history of abdominal pain,obstructive jaundice, itching,
      and fever. The patient had undergone choledochal cyst excision and Roux-en-Y
      hepatico-jejunostomy 25 years previously and had now developed signet-ring cell
      carcinoma along with cholangiocarcinoma at the anastomotic site. DIAGNOSES::
      signet-ring cell carcinoma along with cholangiocarcinoma. INTERVENTIONS:
      Interventions included laparotomy with evacuation,blood transfusion,and other
      adjuvant therapy. OUTCOMES: The patient died five months later. LESSONS: Surgery
      is the best treatment for CCCs, and the surgeon should try to remove as much as
      of the bile duct cyst as possible.

PMID- 29465586
TI  - YiQiFuMai injection for chronic heart failure: Protocol for a systematic review
      and meta-analysis.
AB  - BACKGROUND: Chronic heart AQ4 failure (CHF) is the final stage of various heart
      diseases. YiQiFuMai injection (YQFMI) has been widely applied in the treatment of
      CHF. However, to our knowledge, there has been no systematic review or meta
      analysis of randomized controlled trails (RCTs) regarding the effectiveness of
      this treatment. Here, we provide a protocol to evaluate the efficacy and safety
      of YQFMI for CHF. METHODS: To evaluate the clinical efficacy of YQFMI in treating
      CHF, 2 researcher members will independently search the RCTs in the following 8
      Chinese and English databases, in which the data collection will be from the time
      when the respective databases were established to January 2018. The databases
      will include MEDLINE, EMBASE, Cochrane CENTRAL, CINAHL, the Chinese Biomedical
      Literature Database, the China National Knowledge Infrastructure, VIP Information
      and Wanfang Data. The therapeutic effects according to the mortality and the New
      York Heart Association (NYHA) function classification will be accepted as the
      primary outcomes. We will use RevMan V.5.3 software as well to compute the data
      synthesis carefully when a meta-analysis is allowed. RESULTS: This study will
      provide a high-quality synthesis of current evidence of YQFMI for CHF from
      several aspects including mortality, NYHA function classification. CONCLUSION:
      The conclusion of our systematic review will provide evidence to judge whether
      YQFMI is an effective intervention for CHF.PROSPERO registration number: PROSPERO
      CRD42017079696.

PMID- 29465587
TI  - Systemic-pulmonary arteriovenous fistulae with pulmonary hypertension: A case
      report.
AB  - BACKGROUND: Arteriovenous (AV) fistulae is an extremely rare disease of vascular
      malformation that involves fistulae formation between the systemic and pulmonary
      AV systems. CASE REPRESENTATION: This case report describes a rare systemic
      pulmonary AV fistulae of congenital origin, accompanied by pulmonary
      hypertension, as determined by aortic angiography and echocardiography.
      CONCLUSION: Characteristics, diagnosis, and therapeutic approaches of this rare
      abnormality are explored.

PMID- 29465588
TI  - Chart validation of inpatient International Classification of Diseases, Ninth
      Revision, Clinical Modification (ICD-9-CM) administrative diagnosis codes for
      venous thromboembolism (VTE) among intravenous immune globulin (IGIV) users in
      the Sentinel Distributed Database.
AB  - The Sentinel Distributed Database (SDD) is a database of patient administrative
      healthcare records, derived from insurance claims and electronic health records,
      sponsored by the US Food and Drug Administration for evaluation of medical
      product outcomes. There is limited information on the validity of diagnosis codes
      for acute venous thromboembolism (VTE) in the SDD and administrative healthcare
      data more generally.In this chart validation study, we report on the positive
      predictive value (PPV) of inpatient administrative diagnosis codes for acute VTE
      pulmonary embolism (PE) or lower-extremity or site-unspecified deep vein
      thrombosis (DVT)-within the SDD. As part of an assessment of thromboembolic
      adverse event risk following treatment with intravenous immune globulin (IGIV),
      charts were obtained for 75 potential VTE cases, abstracted, and physician
      adjudicated.VTE status was determined for 62 potential cases. PPVs for lower
      extremity DVT and/or PE were 90% (95% CI: 73-98%) for principal-position
      diagnoses, 80% (95% CI: 28-99%) for secondary diagnoses, and 26% (95% CI: 11-46%)
      for position-unspecified diagnoses (originating from physician claims associated
      with an inpatient stay). Average symptom onset was 1.5 days prior to hospital
      admission (range: 19 days prior to 4 days after admission).PPVs for principal and
      secondary VTE discharge diagnoses were similar to prior study estimates. Position
      unspecified diagnoses were less likely to represent true acute VTE cases.

PMID- 29465589
TI  - High-dose tigecycline for the treatment of nosocomial carbapenem-resistant
      Klebsiella pneumoniae bloodstream infections: A retrospective cohort study.
AB  - Carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) has
      become increasingly frequent threat recently, especially in the intensive care
      unit (ICU). High-dose tigecycline (TGC) regimen is proposed due to the limitation
      of treatment options. We investigated the efficacy and safety of high-dose TGC
      combination regimens for treating CRKP BSI. Furthermore, the risk factors for
      mortality were also determined.This was a single center retrospective cohort
      study conducted from 2014 to 2016. A total of 40 patients with nosocomial CRKP
      BSI admitted to the ICU were included; they were classified into two groups
      according to the treatment regimens with high-dose TGC (HD group) or not (non-HD
      group). In-hospital mortality rates and microbiologic responses from both groups
      were reviewed and compared. Besides, the survival and non-survival groups were
      compared to identify the risk factors of mortality.Twenty-three patients
      constituted the HD group (high-dosage TGC regimen was administered as 200 mg
      loading dose followed by 100 mg every 12 h) and 17 patients constituted the non
      HD group (standard dose TGC therapy as 100 mg loading dose followed by 50 mg
      every 12 h and other antibiotics). The in-hospital mortality was 52.2% in the HD
      group and 76.5% in the non-HD group (P = .117). The Kaplan-Meier test showed
      significantly longer survival times in the HD group (mean: 83 days vs 28 days; P
      = .027). Microbiological eradication was observed in 13 patients (56.5%) in the
      HD group and 6 patients (36.3%) in the non-HD group (P = .184). A smaller
      fraction of patients in the HD group were subjected to vasoactive therapy (52.2%
      vs 88.2%; P = .016) compared to the non-HD group. There was no significant
      difference in the manifestation of adverse effects between the two groups. In the
      multivariate analysis, multiple organ dysfunction syndrome (MODS), vasoactive
      therapy, and exposure to carbapenems were regarded as the independent predictors
      of mortality.A therapeutic regimen consisting of a high dose of TGC was
      associated with significantly longer survival time and numerically lower
      mortality in CRKP BSI. Adverse events were not increased with the double dose
      therapy.

PMID- 29465590
TI  - Relationship between bone turnover markers and the heel stiffness index measured
      by quantitative ultrasound in middle-aged and elderly Japanese men.
AB  - The aim of the present study was to investigate the age-related patterns and the
      relationships between serum levels of tartrate-resistant acid phosphatase-5b
      (TRACP-5b) or bone-specific alkaline phosphatase (BAP), and the heel stiffness
      index measured by quantitative ultrasound (QUS) in 429 Japanese men, with special
      emphasis on 2 age groups (40-59 years and 60 years or over). The heel stiffness
      index (bone mass) was measured by QUS. Serum samples were collected, and TRACP-5b
      and BAP levels were measured. The stiffness index was significantly decreased
      with age. Log (TRACP-5b) was significantly increased with age, but Log (BAP) was
      stable. Generalized linear models showed that higher levels of Log (TRACP-5b) and
      Log (BAP) were correlated with a lower stiffness index after adjusting for
      covariates in men aged 60 years or over, but not in men aged 40 to 59 years. In
      conclusion, higher rates of bone turnover markers were associated with a lower
      stiffness index only in elderly men. These results may indicate a different
      mechanism of low bone mass among different age groups of men.

PMID- 29465591
TI  - A study on risk factors and diagnostic efficiency of posthepatectomy liver
      failure in the nonobstructive jaundice.
AB  - Liver failure remains as the most common complication and cause of death after
      hepatectomy, and continues to be a challenge for doctors.t test and chi test were
      used for single factor analysis of data-related variables, then results were
      introduced into the model to undergo the multiple factors logistic regression
      analysis. Pearson correlation analysis was performed for related postoperative
      indexes, and a diagnostic evaluation was performed using the receiver operating
      characteristic (ROC) of postoperative indexes.Differences in age, body mass index
      (BMI), portal vein hypertension, bile duct cancer, total bilirubin, alkaline
      phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), operation time,
      cumulative portal vein occlusion time, intraoperative blood volume, residual
      liver volume (RLV)/entire live rvolume, ascites volume at postoperative day
      (POD)3, supplemental albumin amount at POD3, hospitalization time after
      operation, and the prothrombin activity (PTA) were statistically significant.
      Furthermore, there were significant differences in total bilirubin and the
      supplemental albumin amount at POD3. ROC analysis of the average PTA, albumin
      amounts, ascites volume at POD3, and their combined diagnosis were performed,
      which had diagnostic value for postoperative liver failure (area under the curve
      (AUC): 0.895, AUC: 0.798, AUC: 0.775, and AUC: 0.903).Preoperative total
      bilirubin level and the supplemental albumin amount at POD3 were independent risk
      factors. PTA can be used as the index of postoperative liver failure, and the
      combined diagnosis of the indexes can improve the early prediction of
      postoperative liver failure.

PMID- 29465592
TI  - Urinary metalloproteinases and tissue inhibitors of metalloproteinases as
      potential early biomarkers for renal fibrosis in children with nephrotic
      syndrome.
AB  - In chronic glomerulopathies, renal fibrosis (RF) results from extracellular
      matrix remodeling processes regulated by matrix metalloproteinases (MMP) and
      tissue inhibitors of metalloproteinases (TIMP). We assessed urinary (u-) and
      serum (s-) MMP-1, -2, -9, TIMP-1, -2 concentrations and MMP-1, -2, -9/TIMP-1, -2
      ratios in children with nephrotic syndrome. Steroid-dependent and steroid
      resistant nephrotic patients (SDNS-Ps and SRNS-Ps, respectively) were compared
      with respect to measured parameters. The correlations of measured parameters with
      magnitude of proteinuria and histopathological diagnosis were determined.The
      study comprised of 39 children with nephrotic syndrome and 20 healthy controls.
      Twenty-three patients had SDNS and 16 ones-SRNS. The concentrations MMPs and
      TIMPs were measured using enzyme-linked immunosorbent assay.In nephrotic
      patients, higher u-MMP-1, -2, -9/creatinine ratios and u-TIMP-1, -2/creatinine
      ratios were observed as compared with controls. Nephrotic children were also
      characterized by lower MMP-1, -2, -9/TIMP-1 ratios. In SRNS-Ps, u-MMP
      2/creatinine ratio and u-TIMP-1/creatinine ratio were higher as compared with
      SDNS-Ps. Magnitude of proteinuria correlated positively with u-MMP-2/creatinine
      ratio and negatively with u-MMP-2/TIMP-1. In minimal change disease (MCD)
      patients as compared with those with other glomerulopathies, there was higher u
      MMP-2/TIMP-1 ratio. No significant differences in s-MMPs, s-TIMPs, and s
      MMPs/TIMPs ratios between nephrotic patients and controls were observed.Children
      with nephrotic syndrome are characterized by increased u-fibrotic biomarkers
      excretions. U-MMP-1, -2, -9 excretions and u-MMP-2/TIMP-1 ratio may become
      potential early biomarkers for RF. SRNS-Ps, those with heavier proteinuria and
      other than MCD glomerulopathies, seem to be more susceptible to early RF.

PMID- 29465593
TI  - Preoperative fluid management in traumatic shock: A retrospective study for
      identifying optimal therapy of fluid resuscitation for aged patients.
AB  - Fluid resuscitation was used on aged patients with traumatic shock in their early
      postoperative recovery. The present study aimed to assess whether different fluid
      resuscitation strategies had an influence on aged patients with traumatic shock.A
      total of 219 patients with traumatic shock were recruited retrospectively.
      Lactated Ringer and hydroxyethyl starch solution were transfused for fluid
      resuscitation before definite hemorrhagic surgery. Subjects were divided into 3
      groups: group A: 72 patients were given aggressive fluid infusion at 20 to 30
      mL/min to restore normal mean arterial pressure (MAP) of 65 to 75 mm Hg. Group B:
      72 patients were slowly given restrictive hypotensive fluid infusion at 4 to 5
      mL/min to maintain MAP of 50 to 65 mm Hg. Group C: 75 patients were given
      personalized infusion to achieve MAP of 75 to 85 mm Hg. Preoperative infusion
      volume, preoperative MAP, optimal initial points for surgery, postoperative shock
      time and mortality rates at 6 and 24 hours after surgery were determined.No
      significant difference in clinical characteristics was found among the 3 groups.
      Amount of preoperative infusion was considerably lower in the restrictive group
      (P < .01, compared with group A). A significant difference in preoperative
      infusion volume was found between the personalized and other 2 groups (P < .01,
      compared with groups A and B). Patients in the personalized resuscitation group
      achieved a higher preoperative MAP (P < .01 compared with Group B; P < .05,
      compared with group A) and required less prepared time for surgery (P < .01
      compared with groups A and B). In addition, a lower mortality rate at 6 and 24
      hours after operation was observed in the subjects with personalized therapy (P <
      .05, compared with group B).Personalized management of fluid resuscitation in
      traumatized aged patients with appropriate volume and speed of fluid transfusion,
      suggesting increased survival rate and less prepared time for surgery.

PMID- 29465594
TI  - Understanding the productive author who published papers in medicine using
      National Health Insurance Database: A systematic review and meta-analysis.
AB  - Many researchers used National Health Insurance database to publish medical
      papers which are often retrospective, population-based, and cohort studies.
      However, the author's research domain and academic characteristics are still
      unclear.By searching the PubMed database (Pubmed.com), we used the keyword of
      [Taiwan] and [National Health Insurance Research Database], then downloaded 2913
      articles published from 1995 to 2017. Social network analysis (SNA), Gini
      coefficient, and Google Maps were applied to gather these data for visualizing:
      the most productive author; the pattern of coauthor collaboration teams; and the
      author's research domain denoted by abstract keywords and Pubmed MESH (medical
      subject heading) terms.Utilizing the 2913 papers from Taiwan's National Health
      Insurance database, we chose the top 10 research teams shown on Google Maps and
      analyzed one author (Dr. Kao) who published 149 papers in the database in 2015.
      In the past 15 years, we found Dr. Kao had 2987 connections with other coauthors
      from 13 research teams. The cooccurrence abstract keywords with the highest
      frequency are cohort study and National Health Insurance Research Database. The
      most coexistent MESH terms are tomography, X-ray computed, and positron-emission
      tomography. The strength of the author research distinct domain is very low (Gini
      < 0.40).SNA incorporated with Google Maps and Gini coefficient provides insight
      into the relationships between entities. The results obtained in this study can
      be applied for a comprehensive understanding of other productive authors in the
      field of academics.

PMID- 29465595
TI  - Discordant CSF/plasma HIV-1 RNA in individuals on virologically suppressive
      antiretroviral therapy in Western India.
AB  - Aim of this study was to estimate the prevalence of cerebrospinal fluid
      (CSF)/Plasma HIV-1 RNA discordance in virologically suppressed individuals
      presenting with incident neurologic symptoms.In this retrospective cohort study
      conducted between March 1, 2009, and March 1, 2017, HIV-1 infected adults exposed
      to atleast 12 months of antiretroviral therapy (ART) and having plasma viral load
      (VL) <1000 copies/mL (virologically suppressed) were included. Among these,
      individuals presenting with neurologic symptoms during follow-up were assessed
      for CSF/Plasma HIV-1 RNA discordance by measuring HIV-1 RNA in collected plasma
      and CSF samples. CSF/plasma HIV-1 RNA discordance was defined as either
      detectable CSF HIV-1 RNA (VL > 20 copies/mL) with an undetectable plasma RNA
      (complete viral suppression, VL <=20 copies/mL) or CSF HIV-1 RNA >= 0.5 log10
      higher than plasma RNA when plasma VL was between 20 and 1000 copies/mL (low
      level viremia, LLV).Out of 1584 virologically suppressed patients, 71 (4.4%)
      presented with incident neurologic symptoms. Twenty out of 71 (28.2%) patients
      were diagnosed with CSF/Plasma HIV-1 discordance. Median plasma and CSF VL in
      patients with discordance was 120 [interquartile range (IQR): <20 to 332.5] and
      4250 (IQR: 2550.0- 9615.0) copies/mL, respectively. All 9 individuals in which
      CSF HIV-1 genotypic resistance testing was done showed mutations that would
      compromise efficacy of prescribed ART regimen. Prevalence of CSF/plasma HIV-1 RNA
      discordance was higher among neurologically symptomatic patients with plasma LLV
      as compared with those with complete viral suppression (70% vs 11.8%, P < .001).
      The risk of discordance was also greater in patients who received protease
      inhibitor (PI) containing ART (P < .001) and those on ART regimens with central
      nervous system (CNS) penetration effectiveness (CPE) value <6 (P =
      .006).CSF/plasma HIV-1 RNA discordance indicates replication of HIV-1 that has
      adapted to the CNS or has developed antiretroviral drug resistance. Larger
      studies should be performed to study incidence of discordance in India. This will
      help in managing patients presenting with neurologic symptoms on suppressive ART
      with appropriate neuroeffective therapy.

PMID- 29465596
TI  - Tianma Gouteng decoction for essential hypertension: Protocol for a systematic
      review and meta-analysis.
AB  - BACKGROUND: Essential hypertension is one of the most common chronic diseases, as
      well as one of the leading risk factors for cardio-cerebrovascular diseases.
      Tianma Gouteng decoction has been commonly used in clinical practice for patients
      with essential hypertension. It is important to update the search and evaluation
      to provide the best available evidence for essential hypertension. Here, we
      provide a protocol to evaluate the efficacy and safety of Tianma Gouteng
      decoction (TGD) for essential hypertension. METHODS: Retrieve literature on the
      TGD treatment for essential hypertension in the databases including PubMed,
      Cochrane Library, EMBASE, Chinese Biomedical database (CBM), Chinese National
      Knowledge Infrastructure (CNKI), Wanfang database, and Chinese Science and
      Technology Periodical database (VIP) on computer. The literature to be collected
      will be those published from the time when the respective databases were
      established to January 2018. The therapeutic effects according to the blood
      pressure (BP) will be accepted as the primary outcomes. We will use RevMan V.5.3
      software as well to compute the data synthesis carefully when a meta-analysis is
      allowed. RESULTS: This study will provide a high-quality synthesis of current
      evidence of TGD for essential hypertension from several aspects including BP,
      life quality, heart rate, and adverse events. CONCLUSION: The conclusion of our
      systematic review will provide evidence to judge whether TGD is an effective
      intervention for patient with essential hypertension. PROSPERO REGISTRATION
      NUMBER: PROSPERO CRD 42018082319.

PMID- 29465597
TI  - Chinese herbal injections for heart failure: A protocol for systematic review and
      network meta-analyses.
AB  - BACKGROUND: Chinese herbal injections (CHIs) are commonly used for the treatment
      of heart failure in China. Due to the variety of CHIs used in clinic, selecting a
      suitable CHI for patients with heart failure is vital. This study aims to assess
      and compare the effect of different CHIs for heart failure using network meta
      analysis (NMA). METHODS: Six electronic databases, including PubMed, the Cochrane
      Central Register of Controlled Trials, Embase, China National Knowledge
      Infrastructure, Wanfang, and Chinese Biomedical Literature Database will be
      search from inception to January 2018. Randomized controlled trial (RCT)
      comparing CHI with another CHI will be included. The primary outcome will be
      changes in heart function classification and left ventricular ejection fraction.
      Risk of bias assessment of the included RCTs will be conducted according to the
      Cochrane Handbook 5.1.0. A Bayesian NMA will be performed using WinBUGS 14
      software and the result figures will be generated using Stata 13 software. GRADE
      will be used to explore the quality of evidence. RESULTS: The results of this NMA
      will be published in a peer-reviewed journal. CONCLUSION: Our study will generate
      evidence of CHIs for patients with heart failure and provide suggestions for
      Chinese medicine clinical practice or guideline. ETHICS AND DISSEMINATION: Ethics
      approval and patient consent are not required because this study is an NMA based
      solely on the published literature. The results of this NMA will be submitted to
      a peer-reviewed journal. PROTOCOL REGISTRATION NUMBER: PROSPERO CRD 42018086740.

PMID- 29465598
TI  - Tuina for osteoporosis: A systematic review protocol.
AB  - BACKGROUND: Osteoporosis is one kind of commonly and frequently occurring global
      disease accompanying with serious complications. As a branch of the subject of
      Acupuncture-Tuina, tuina is widely applied for osteoporosis alone or combined
      with other methods in China and other nations while its effective evidence is not
      clear. Hence, this systematic review protocol purpose is to evaluate the value of
      its efficacy and safety for osteoporosis. METHODS: This systematic review and
      meta-analysis will be performed by means of electronic databases including
      Cochrane Library, Medline, Cochrane Library, Web of Science, EBASE, Springer, WHO
      International Clinical Trials Registry Platform (ICTRP), China National Knowledge
      Infrastructure (CNKI), Wanfang database, Chinese Biomedical Literature Database
      (CBM), Chinese Scientific Journal Database (VIP) and others with valid search
      strategy probably. The assessment of bias risk, data synthesis, subgroup
      analysis, and meta-analyses will be conducted using RevMan V.5.3.5 software.
      RESULTS: This systematic review will present a high-quality evidence for
      clinicians and might be the first to evaluate the efficacy and safety of tuina
      for osteoporosis including alleviation of pain, adverse event, spinal motor
      function improvement as well as improvement of self-care ability and daily
      living. CONCLUSION: This protocol will determine whether or not tuina is an
      effective and safety intervention for osteoporosis.

PMID- 29465599
TI  - Primary pulmonary lymphoepithelioma-like carcinoma in non-endemic region: A case
      report and literature review.
AB  - RATIONALE: Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of
      lung squamous cell carcinoma. In situ hybridization test for Epstein-Bar virus
      encoded RNA (EBER) is generally used for distinguishing it from other lung
      cancers. Although plasma EBV DNA quantification has been widely used as a tumor
      biomarker in nasopharyngeal carcinoma (NPC), only a limiting number of studies
      have suggested that plasma EBV DNA quantification may be used as a tumor marker
      in pulmonary LELC patients. PATIENT CONCERNS: We report two female patients
      diagnosed as poorly differentiated squamous cell carcinoma, subsequently, their
      further histological examinations showed that tumor cells were EBER positive and
      plasma EBV DNA was detectable. DIAGNOSES: Two patients was diagnosed with
      advanced pulmonary LELC. INTERVENTIONS: The patients were treated with
      chemotherapy and chemoradiotherapy respectively. OUTCOMES: Both patients
      responded well to our treatment, in accordance with their decreased EBV DNA
      level. LESSONS: Pulmonary LELC is a rare type of lung cancer which is sensitive
      to chemoradiotherapy, especially in late staged patients.

PMID- 29465600
TI  - A novel endobronchial approach to massive hemoptysis complicating silicone Y
      stent placement for tracheobronchomalacia: A case report.
AB  - RATIONALE: Airway stabilization for severe, symptomatic tracheobronchomalacia
      (TBM) may be accomplished by silicone Y-stent placement. Common complications of
      the Y-stent include mucus plugging and granulation tissue formation. PATIENT
      CONCERNS: We describe a rare case of massive hemoptysis originating from a
      silicone Y-stent placed for TBM. DIAGNOSES: An emergent bronchoscopy showed an
      actively bleeding, pulsatile vessel at the distal end of the left bronchial limb
      of the Y-stent. It was felt that the bleeding was caused by, or at least impacted
      by, the distal left bronchial limb of the Y-stent eroding into the airway wall.
      INTERVENTIONS: We hypothesized that placement of oxidized regenerated cellulose
      (ORC) would provide initial hemostasis, and the subsequent placement of a
      biocompatible surgical sealant would lead to definitive resolution. OUTCOMES: ORC
      provided sufficient hemostasis and the subsequent synthetic polymer reinforced
      the tissue for complete cessation of the bleed. LESSONS: The combined use of ORC
      and a biocompatible surgical sealant provided long-term management for life
      threatening hemoptysis, and potentially morbid procedures such as embolization or
      surgery were avoided by advanced endobronchial therapy.

PMID- 29465601
TI  - Postoperative hemorrhage caused by portal hypertension associated with autoimmune
      pancreatitis: A case report.
AB  - RATIONALE: Autoimmune pancreatitis is a form of chronic pancreatitis,
      characterized by diffused enlargement of the pancreas and irregular narrowing of
      the main pancreatic duct. The theory that portal hypertension is associated with
      autoimmune pancreatitis has not been emphasized. In addition, only a few studies
      report that the gastrointestinal tract hemorrhage caused by portal hypertension
      is associated with autoimmune pancreatitis. PATIENT CONCERNS: The patient was a
      61-year-old male with pancreas occupying lesion detected in a physical
      examination. Preoperative CT showed portal vein diameter increased significantly
      (1.6 cm) and the junction of splenic and portal vein was capsuled by lesions and
      the splenic vein became thin. The Whippie procedure was performed for the
      correction of the lesion. The pancreatic tissue showed chronic inflammation and
      lymphocytic infiltration and fibrosis, and abundant IgG4 cells. After the
      surgery, the patient suffered twice from postoperative hemorrhage (9 and 16 mos).
      DIAGNOSES: Postoperative hemorrhage, autoimmune pancreatitis. INTERVENTION:
      Electronic gastroscopy, exploratory laparotomy, and titanium clips were used
      simultaneously to stop the bleeding. OUTCOMES: The patient recovered well after
      the surgery. LESSONS: In this study, we present the case of repeated
      postoperative hemorrhage (9 and 16 mos). We discussed the correlation between
      postoperative hemorrhage and autoimmune pancreatitis, and the cause of
      postoperative hemorrhage.

PMID- 29465602
TI  - Pleomorphic liposarcoma: An analysis of 6 case reports and literature review.
AB  - RATIONALE: Pleomorphic liposarcoma (PLS), is a rare subtype of liposarcoma, and
      is considered to be of the highest malignancy grade. PATIENT CONCERNS: We aimed
      to analyze the clinical features, diagnosis, treatment, and recurrence of the 6
      cases of PLS. DIAGNOSES: Six cases with confirmed pathological PLS presented at
      out hospital from January 2003 to January 2017. The postoperative pathology of 5
      cases confirmed PLS, and the other was confirmed as PLS with well-differentiated
      liposarcoma. INTERVENTIONS: All 6 patients underwent complete tumor resection at
      the time of the first definite diagnosis, and one of them had underwent 3 cycles
      of chemotherapy treatment. OUTCOMES: There were 4 cases with local recurrence and
      surgery was repeated after the first radical excision. One case was not recurrent
      after 27 months post-operation, and the other was lost. The shortest recurrence
      time of all of these cases was 4 months, and the longest was 29 months after the
      first radical surgery. LESSONS: PLS is a rare and high-grade malignancy with high
      recurrence, poor prognosis, and its treatment is still highly controversial. More
      studies are required to determine the appropriate treatment and therapeutic
      strategies to improve the survival rate of patients with PLS, as the disease is
      associated with frequent relapse.

PMID- 29465603
TI  - Postoperative delirium after partial laryngectomy in a middle-aged patient: A
      case report.
AB  - RATIONAL: Postoperative delirium is a common occurrence in older patients.
      However, reports of postoperative delirium in middle-aged patients are limited,
      and the underlying mechanism of delirium in this patient population is not clear.
      PATIENT CONCERNS: A 45-year-old man who developed postoperative delirium on the
      second day after partial laryngectomy. Interviews of the surgical team, patient,
      and patient's spouse revealed that the patient was psychologically stressed, but
      had not been diagnosed or treated. The patient also suffered impairment in
      physiological functioning and sleep disturbance after surgery. DIAGNOSIS:
      Postoperative delirium. INTERVENTIONS: The postoperative delirium was treated
      with an antipsychotic drug. OUTCOMES: The patient recovered well. LESSONS:
      Preoperative psychological stress, which is often undiagnosed and untreated, can
      increase the risk of postoperative delirium in middle-aged patients undergoing
      laryngectomy. Therefore, screening for psychological stress and implementing
      strategies to prevent delirium should be considered for patients who undergo
      laryngectomy, even if they are not in high-risk older age groups.

PMID- 29465604
TI  - Double laparoscopy assisted cylindrical abdominal-perineal resection for low
      rectal cancer with 4 cases report.
AB  - INTRODUCTION: Rectal cancer is a common cancer worldwide. Low rectal cancer
      exhibits a tendency for recurrence. Surgical resection is an important treatment
      for rectal cancer. Cylindrical abdominal-perineal resection is suitable for
      patients with low rectal cancer and has helped improve the prognosis of these
      patients. However, there are some difficulties during the operation. Especially
      the perineal area operation cannot be performed under direct vision, which
      affects the quality of surgical resection. To resolve these constraints, our
      group designed double laparoscopy assisted cylindrical abdominal-perineal
      resection for low rectal cancer. CONCLUSION: The procedure effectively solved
      these problems and reduced the operation time with no increase in surgery
      complications.

PMID- 29465606
TI  - Test-Retest Reliability and Concurrent Validity of Athletic Performance Combine
      Tests in 6-15-Year-Old Male Athletes.
AB  - Gillen, ZM, Miramonti, AA, McKay, BD, Leutzinger, TJ, and Cramer, JT. Test-retest
      reliability and concurrent validity of athletic performance combine tests in 6-15
      year-old male athletes. J Strength Cond Res 32(10): 2783-2794, 2018-Athletic
      performance combine tests are used by high school, collegiate, and professional
      American football programs to evaluate performance; however, limited evidence is
      available on performance combine test results in youth athletes. The purposes of
      this study were to report test-retest reliability statistics and evaluate
      concurrent validity among combine performance tests in 6-15-year-old male
      athletes. Sixty-nine young male athletes (mean +/- SD; age = 10.9 +/- 2.1 years,
      height = 154.4 +/- 13.6 cm, body mass = 46.8 +/- 16.0 kg) were divided into 3 age
      groups: 6-9 years (n = 16), 10-11 years (n = 26), and 12-15 years (n = 27).
      Participants completed 2 attempts of the vertical jump (VJ), broad jump (BJ), pro
      agility (PA), L-cone (LC) drill, and 10-, 20-, 40-yd dashes. The results
      indicated that the older age groups performed better on most performance
      assessments compared with the 6-9-year group (p <= 0.05). The combine tests
      demonstrated consistently adequate reliability for all age groups, except for the
      10-yd dash, which was deemed unreliable. Evidence of concurrent validity, and
      possible measurement redundancy were observed in the VJ vs. BJ, PA vs. LC, and 20
      vs. 40 yd, but zero- and first-order partial correlations suggested that only the
      PA and LC were redundant, and the PA may be superior for this age group over the
      LC. Although the VJ and BJ provide independent performance information regarding
      lower-body power, questions regarding the redundancy of the 20 vs. 40 yd remain
      unanswered from a measurement perspective.

PMID- 29465605
TI  - A false-positive I-131 finding of duodenum diverticulum in thyroid cancer
      evaluation by SPECT/CT: A case report.
AB  - RATIONALE: Iodine-131 (I-131) is a sensitive marker for the detection of
      differentiated thyroid cancer (DTC). I-131 whole-body scintigraphy (WBS) has been
      used widely in evaluation of DTC patient. However, I-131 WBS exists many false
      positive uptake of I-131 because radioiodine uptake can also be seen in healthy
      tissue or in a variety of benign and malignant non-thyroidal tumors. PATIENT
      CONCERNS: A 44-year-old woman with a papillary thyroid carcinoma for the purpose
      of ablation therapy after a total thyroidectomy. I-131 WBS showed intensive
      uptake by thyroid remnant. Meanwhile, a focus of increased activity was seen in
      right upper abdomen. DISGNOSES, INTERVENTIONS AND OUTCOMES: Based on an I-131
      single-photon emission computed tomography/computed tomography (SPECT/CT) fusion
      imaging combining a Tc-99m pertechnetate dynamic SPECT scan and SPECT/CT fusion
      imaging with oral administration of iodine contrast agent, a descending duodenum
      diverticulum was diagnosed. This patient was then treated with conservative
      treatment, such as diet regulation, rest, appropriate use of antacids and
      antispasmodic agents, etc. So far, she recovered uneventfully with no any
      complications. LESSONS: Duodenum diverticulum is a rare false-positive uptake of
      I-131, it might be a diagnostic challenge when there are many false-positive
      uptake of I-131 in evaluation of DTC. So it must be significant to be familiar
      with these physiologic and pathologic variants of I-131 uptake and make further
      efforts to accurately interpret radioiodine scintigraphy results.

PMID- 29465607
TI  - The Efficacy of Heart Rate Variability in Tracking Travel and Training Stress in
      Youth Female Rowers: A Preliminary Study.
AB  - : (248 words)Heart rate (HR) variability (HRV) is a reliable indicator of cardiac
      parasympathetic activity and has been used in athletic populations to measure
      training adaptations. To date, there is limited research showing whether HRV is
      practical in youth female athletes and rowers during short periods of overload
      training. PURPOSE: The purpose of this study was to evaluate the practicality of
      HRV in documenting training responses during a period of overload training in
      youth female rowers. METHODS: Time domain (standard deviation of RR intervals,
      SDNN; root mean square of successive differences, RMSSD) and nonlinear (SD1)
      indices of HRV were recorded during baseline training, daily during the six-day
      training camp, and one week after the camp in 5 athletes from an elite high
      school rowing team. Training duration and rate of perceived exertion (RPE) were
      recorded to document training load. RESULTS: Training load during the camp was
      76% above the athlete's normal workload (2258 +/- 459 vs. 1280 +/- 356 a.u.).
      Using progressive statistics, cardiac vagal activity (RMSSD and SD1) was very
      likely reduced during each day of the camp when compared with baseline training,
      though returned to baseline within a week of the training camp. Interestingly,
      SDNN was reduced throughout the training camp and remained reduced up to a week
      after the training camp (78% likely, ES=0.32). CONCLUSIONS: These insights add
      value to HRV's use in youth sport and provides coaches with an easy, cost
      effective means to monitor the physiological response to training, allowing fine
      tuning of training, potentially enhancing performance.

PMID- 29465608
TI  - Muscle Activation Patterns of Lower-Body Musculature Among 3 Traditional Lower
      Body Exercises in Trained Women.
AB  - Korak, JA, Paquette, MR, Fuller, DK, Caputo, JL, and Coons, JM. Muscle activation
      patterns of lower-body musculature among 3 traditional lower-body exercises in
      trained women. J Strength Cond Res 32(10): 2770-2775, 2018-The deadlift and back
      and front squats are common multijoint, lower-body resistance exercises that
      target similar musculature. To our knowledge, muscle activity measured using
      surface electromyography has never been analyzed among these 3 exercises.
      Furthermore, most literature examining this topic has included male participants
      creating a void in the literature for the female population. Knowledge of lower
      body muscle activation among these 3 exercises can aid coaches, trainers, and
      therapists for training and rehabilitative purposes. Trained women (n = 13)
      completed 2 days of testing including a 1-repetition maximum (1RM) estimation, an
      actual 1RM, and 3 repetitions at 75% 1RM load for the deadlift and back and front
      squats. Muscle activity of the 3 repetitions of each muscle was averaged and
      normalized as a percentage to the 1RM lifts for the deadlift and front and back
      squats. Five separate repeated-measure analysis of variances were performed
      indicating muscle activity of the gluteus maximus (GM) differed among the 3
      exercises (p = 0.01, (Equation is included in full-text article.)= 0.39).
      Specifically, post hoc analysis indicated greater muscle activity during the
      front squat (M = 94%, SD = 15%) compared with the deadlift (M = 72%, SD = 16%; p
      <= 0.05) in the GM. No significant differences were observed among the lifts in
      the vastus medialis, vastus lateralis, biceps femoris, and rectus femoris.
      Strength and conditioning specialist and trainers can use these findings by
      prescribing the front squat to recruit greater motor units of the GM.

PMID- 29465609
TI  - Novel Myelin Protein Zero Mutation in 3 Generations of Vermonters With
      Demyelinating Charcot-Marie-Tooth Disease.
AB  - OBJECTIVES: We report the clinical phenotype in 3 consecutive generations with
      demyelinating Charcot-Marie-Tooth disease that possess a novel sequence variant
      of myelin protein zero (MPZ). METHODS: Family members from 3 consecutive
      generations were interviewed, examined, and studied with electrodiagnostic
      testing. Commercially available next-generation sequencing was performed for the
      proband. Single-gene analysis was performed for the remaining family members.
      RESULTS: All patients demonstrated symmetric distal weakness; symmetric distal
      sensory loss; and diminished deep tendon reflexes. Electrodiagnostic testing was
      consistent with primary distal demyelination with secondary axon loss. Genetic
      testing identified a novel base-pair substitution of MPZ (c.314C>T), resulting in
      a missense variant (p.Pro105Leu). CONCLUSIONS: The novel MPZ base-pair
      substitution in this family is associated with inherited distal demyelinating
      neuropathy and should be reclassified as pathogenic for Charcot-Marie-Tooth.

PMID- 29465610
TI  - COL6A and LAMA2 Mutation Congenital Muscular Dystrophy: A Clinical and
      Electrophysiological Study.
AB  - OBJECTIVES: COL6A and LAMA2 are subtypes of congenital muscular dystrophy.
      METHODS: Retrospective chart review of clinical findings, spirometry, muscle
      histology, muscle ultrasound, neuroimaging, and Electromyography (EMG)/Nerve
      Conduction Study data in genetically confirmed COL6A and LAMA2 subjects. RESULTS:
      We identified 8 COL6A and 6 LAMA2 subjects: the female-to-male ratio was 1.3:1
      and the mean age was 11.9 +/- 3.6 years. Gross motor delays since birth, proximal
      muscle weakness, and contractures were noted in both groups. Joint hyperlaxity
      and skin changes (follicular hyperkeratosis and muscle biopsy scar thinning) were
      unique to COL6A. Severe scoliosis, macrocephaly, and nonambulatory status were
      common in LAMA2. Increasing age was associated with poor respiratory function in
      COL6A. There was central "cloud appearance" on rectus femoris muscle ultrasound
      in COL6A and white matter T2 hyperintensity on brain magnetic resonance imaging
      in LAMA2. LAMA2 also showed demyelinating polyneuropathy. Neurogenic changes on
      EMG and muscle histology were noted in 37% and 33% of COL6A cases, respectively.
      CONCLUSIONS: COL6A has unique skin changes, central cloud appearance on muscle
      ultrasound. LAMA2 has demyelinating polyneuropathy and white matter changes on
      brain imaging. The presence of neurogenic changes on EMG and muscle histology in
      COL6A suggests motor axonal neuropathy. Genetic testing remains the gold standard
      in confirming COL6A congenital muscular dystrophy.

PMID- 29465612
TI  - Patient With 2 Hematologic Malignancies Presenting as Neurolymphomatosis.
AB  - Peripheral nervous system damage from hematologic malignancies is related to
      neoplastic cells infiltration of peripheral nerves or to monoclonal antibody
      production cross-reacting with peripheral nerves' antigens. Neurolymphomatosis
      (NL), a rare manifestation of hematologic malignancies, occurs when malignant
      cells invade the peripheral nerves leading to various manifestations. Here, we
      report a case of NL with 2 hematologic malignancies in a 79-year-old woman
      presenting with lower extremity pain/weakness. Investigation revealed anemia, IgM
      kappa monoclonal gammopathy, and elevated anti-MAG titer. Electrodiagnostic
      studies were consistent with mononeuropathy multiplex while imaging suggested
      malignancy in her ovaries and right S1 nerve root. Bone marrow and ovarian
      biopsies revealed chronic myelomonocytic leukemia, Waldenstrom macroglobulinemia,
      and diffuse large B-cell lymphoma. She received standard chemotherapy resulting
      in radiographic resolution of disease and symptomatic relief. NL can precede the
      diagnosis of hematologic malignancy but its symptoms are not easily identifiable,
      whereas management depends on the treatment of the underlying tumor.

PMID- 29465611
TI  - Mitochondrial DNA Deletions With Low-Level Heteroplasmy in Adult-Onset Myopathy.
AB  - We report the cases of 2 patients who presented to our Myositis Center with
      myalgias and elevated creatine kinase levels. Muscle biopsy showed pathological
      features consistent with mitochondrial myopathy. In both cases, a single large
      deletion in mitochondrial DNA at low-level heteroplasmy was identified by next
      generation sequencing in muscle tissue. In 1 case, the deletion was identified in
      muscle tissue but not blood. In both cases, the deletion was only identified on
      next-generation sequencing of muscle mitochondrial DNA and missed on array
      comparative genome hybridization testing. These cases demonstrate that next
      generation sequencing of mitochondrial DNA in muscle tissue is the most sensitive
      method of molecular diagnosis for mitochondrial myopathy due to mitochondrial DNA
      deletions.

PMID- 29465613
TI  - What is in the Myopathy Literature?
AB  - This review is focused on recent reports of sporadic inclusion body myositis
      (sIBM), myopathy in patients with human immunodeficiency virus type 1 (HIV)
      infection, and necrotizing autoimmune myopathy with antibodies to signal
      recognition particle. The sIBM articles cover associations with certain genetic
      polymorphisms, the possible pathogenic role of anti-cytosolic 5'-nucleotidase 1A
      antibody, and disease-related burden and health care costs. Another article
      addressed the possible pathogenic role of signal recognition particle antibody in
      necrotizing myopathy. A series of HIV patients with overlapping features of sIBM
      and polymyositis are highlighted as is a report of a patient with HIV and late
      onset rod-body myopathy that may have improved with immunotherapy.

PMID- 29465614
TI  - Radiation-Induced Painful Neurogenic Hypertrophy Treated With Botulinum Toxin A.
AB  - Painful neurogenic hypertrophy is a rare complication of radiation therapy. We
      report a 27-year-old woman with a history of adenoid cystic carcinoma of the
      submandibular gland presented with painful twitching of her left shoulder.
      Electrodiagnostic studies were consistent with a diagnosis of radiation-induced
      spinal accessory nerve hyperactivity. The patient failed conventional medical
      therapy. She was treated with an injection of botulinum toxin A, and within 1
      month experienced significant relief of symptoms. We thus conclude that Botulinum
      toxin is a therapeutic option for the pain associated with radiation-induced
      peripheral nerve hyperactivity.

PMID- 29465615
TI  - Peripheral Vasculitic Neuropathy Associated With Minocycline Use.
AB  - We describe 2 patients presenting with multiplex mononeuritis, associated with
      skin manifestation, secondary to minocycline-induced vasculitis. One of the cases
      is associated neither with lupus nor polyarteritis nodosa. An extensive
      laboratory workup ruled out any possible underlying immunologic disorder.
      Electrodiagnostic studies were conducted to show axonal neuropathy in patchy and
      multifocal distribution consistent with multiplex mononeuritis. This diagnosis
      was confirmed with nerve biopsy. Withdrawing from the offending medication,
      minocycline, improved the patients' clinical condition and the quantitative
      serological measures.

PMID- 29465616
TI  - Asymmetric Muscle Involvement in an Indian Family With Central Core Myopathy.

PMID- 29465617
TI  - Hypoglycemia in a Patient With Facioscapulohumeral Muscular Dystrophy.

PMID- 29465618
TI  - Case of Charcot-Marie-Tooth Type 2C Due to a TRPV4 Gene Mutation With Isolated
      Sudomotor Autonomic Dysfunction.

PMID- 29465619
TI  - Miller-Fisher Syndrome With Botulism Toxin Ingestion: The Ultimate Descending
      Paralysis.

PMID- 29465620
TI  - Coexistence of Ankylosing Spondylitis and Myotonic Dystrophy: Camptocormia or
      Thoracic Ankylosis.

PMID- 29465622
TI  - Autoinflammation.

PMID- 29465623
TI  - The distinct roles of insular subareas in recognition memory: a stereo
      electroencephalography study.
AB  - Previous studies have reported that the insular cortex is involved in recognition
      memory, but it remains unclear which subarea of the insular cortex serves this
      function. To address this question, we examined 14 drug-resistant focal epilepsy
      patients implanted with stereotactic electrodes in the insular cortex. All
      participants performed a delayed match-to-sample task. Event-related potentials
      and spectrograms from each insular subarea were analyzed when the participants
      were exposed to identical (match condition) and different (mismatch condition)
      stimuli. Each of the insular subareas had a significantly different event-related
      potential within the investigated interval of recognition memory under both match
      and mismatch conditions. Moreover, we observed that most of contacts in the left
      anterior insula had a stronger high-gamma response under the mismatch condition
      than the match condition, whereas most of contacts in the right insula had a
      stronger high-gamma response under the match condition than the mismatch
      condition. Thus, distinct roles for each insular subarea in recognition memory
      were found in this study. The right insula appears to subserve recognition memory
      by focusing on processing identical information, whereas the left anterior insula
      seems to subserve conflict monitoring by focusing on processing different
      information.

PMID- 29465624
TI  - Subcortical grey matter structures in multiple sclerosis: what is their role in
      cognition?
AB  - The present study aimed to investigate altered grey matter (GM) and functional
      connectivity (FC) in deep subcortical areas, such as the thalamus and basal
      ganglia, and their relationship with cognitive impairment (CI) in multiple
      sclerosis (MS). Thirty-six patients were neuropsychologically assessed,
      classified as cognitive preserved (CP) and CI, and were compared with 18 healthy
      controls. GM atrophy and FC were observed in 10 predefined functional areas of
      the thalamus and in six of basal ganglia. GM atrophy was prominent in the basal
      ganglia in CI patients compared with CP MS patients. Increased FC was observed
      between the right caudate and the bilateral orbitofrontal cortex in CI versus CP
      patients. The discriminant and correlation analyses showed that the enhanced FC
      observed between the right caudate and the orbitofrontal cortex was closely
      associated with CI in MS patients. In conclusion, reduced GM volume and enhanced
      frontobasal ganglia connectivity are related to cognition in MS patients.

PMID- 29465625
TI  - Spinal bromodomain-containing protein 4 contributes to neuropathic pain induced
      by HIV glycoprotein 120 with morphine in rats.
AB  - The symptoms of HIV-sensory neuropathy are dominated by neuropathic pain. Recent
      data show that repeated use of opiates enhances the chronic pain states in HIV
      patients. Limited attention has so far been devoted to exploring the exact
      pathogenesis of HIV painful disorder and opiate abuse in vivo, for which there is
      no effective treatment. Bromodomain-containing protein 4 (Brd4) is a member of
      the bromodomain and extraterminal domain protein (BET) family and functions as a
      chromatin 'reader' that binds acetylated lysines in histones in brain neurons to
      mediate the transcriptional regulation underlying learning and memory. Here, we
      established a neuropathic pain model of interaction of intrathecal HIV envelope
      glycoprotein 120 (gp120) and chronic morphine in rats. The combination of gp120
      and morphine (gp120/M, for 5 days) induced persistent mechanical allodynia
      compared with either gp120 or morphine alone. Mechanical allodynia reached the
      lowest values at day 10 from gp120/M application, beginning to recover from day
      21. In the model, gp120/M induced overexpression of Brd4 mRNA and protein at day
      10 using RT-qPCR and western blots, respectively. Immunohistochemical studies
      showed that Brd4 at day 10 was expressed in the neurons of spinal cord dorsal
      horn. BET inhibitor I-BET762 dose-dependently increased the mechanical threshold
      in the gp120/M pain state. The present study provides preclinical evidence for
      treating HIV neuropathic pain with opioids using the BET inhibitor.

PMID- 29465626
TI  - Evaluation of the Protective Role for Candida albicans-reactive Immunoglobulin A
      against Oral Fungal Infection.

PMID- 29465627
TI  - A Social Network Analysis of HIV Treatment Partners and Patient Viral Suppression
      in Botswana.
AB  - OBJECTIVE: Many national HIV guidelines recommend that health care providers
      encourage patients to identify a treatment partner from their social network to
      support antiretroviral therapy adherence. This study examined associations of
      patient and treatment partner characteristics with patient viral suppression in
      Botswana. DESIGN: One hundred thirty-one patients [67 (51.1%) virally suppressed
      and 64 (48.9%) not suppressed] and their treatment partners were recruited for
      cross-sectional interviews from one HIV clinic. METHODS: Participants completed
      surveys assessing social network, sociodemographic, and psychosocial
      characteristics. Open-ended questions explored treatment partner relationship
      quality. RESULTS: Multivariate logistic regressions indicated a higher likelihood
      of viral suppression among patients who reported greater average emotional
      closeness to their network members [odds ratio (95% confidence interval) = 3.8
      (1.3 to 11.5), P = 0.02] and whose treatment partners were spouses/partners [odds
      ratio (95% confidence interval) = 2.6 (1.0 to 6.7), P = 0.04]. Qualitative
      analyses indicated that treatment partners of suppressed patients provided both
      medical and nonmedical support, whereas treatment partners of unsuppressed
      patients focused mainly on adherence reminders and appointment accompaniment.
      Treatment partners, especially of unsuppressed patients, requested ongoing
      training and counseling skills. CONCLUSIONS: Additional research is needed to
      further explore effective characteristics of treatment partners to inform HIV
      treatment guidelines. Standard training for treatment partners could include
      medical-related information and counseling education.

PMID- 29465628
TI  - Long-Term Clinical and Computed Tomography Angiographic Follow-up After Totally
      Endoscopic Coronary Artery Bypass Grafting.
AB  - OBJECTIVE: Totally endoscopic coronary artery bypass grafting was shown to be
      feasible and safe, with excellent clinical and angiographic mid-term results.
      Data on long-term outcome are lacking. Therefore, we aimed to investigate the
      long-term rate of major adverse cardiac and cerebrovascular events and left
      internal mammary artery patency rate in patients undergoing arrested heart
      totally endoscopic coronary artery bypass grafting. METHODS: From 2001 to 2012, a
      total of 208 arrested heart-totally endoscopic coronary artery bypass grafting
      patients were prospectively included. Mean +/- SD age was 58.8 +/- 9.4 years, and
      mean +/- SD Society of Thoracic Surgeons score was 0.5 +/- 0.5%. Major adverse
      cardiac and cerebrovascular events were defined as a composite of death,
      myocardial infarction, stroke, re-percutaneous coronary intervention, re-coronary
      artery bypass graft, and target vessel revascularization. Left internal mammary
      artery patency was assessed using cardiac computed tomography and depicted
      according to the established Fitzgibbon classification. Mean +/- SD follow-up was
      6.9 +/- 2.3 years. RESULTS: At 1, 5, and 10 years, survival rate was 100%, 98.3%,
      and 95.8%, respectively. The freedom from clinical events at 1, 5, and 10 years
      were major adverse cardiac and cerebrovascular events (93.5%, 85.9%, and 83.0%),
      myocardial infarction (99.0%, 97.4%, and 95.9%), target vessel revascularization
      (96.0%, 94.3%, and 91.7%), re-percutaneous coronary intervention (94.5%, 91.6%,
      and 84.2%), and re-coronary artery bypass graft (100%, 99.5%, and 99.5%),
      respectively. Left internal mammary artery patency rate at 1, 5, and 10 years was
      100%, 94.9%, and 88.1%, respectively. CONCLUSIONS: Arrested heart-totally
      endoscopic coronary artery bypass grafting shows excellent clinical long-term
      results with a left internal mammary artery patency rate comparable with
      conventional coronary artery bypass graft at 10 years after surgery.

PMID- 29465629
TI  - Comparison of Automated Titanium Fasteners to Hand-Tied Knots in Open Aortic
      Valve Replacement.
AB  - OBJECTIVE: Aortic cross-clamp and cardiopulmonary bypass times are independent
      predictors of postoperative morbidity and mortality. Reducing ischemic times with
      automated titanium fasteners may improve surgical outcomes. This study compared
      operative times and costs of titanium fasteners versus hand-tied knots for
      prosthesis securement in open aortic valve replacement. METHODS: A randomized
      control trial was conducted during a 16-month period at a single university
      medical center. Patients undergoing elective aortic valve replacement were
      randomized to the titanium fastener (n = 37) or hand-tied groups (n = 36).
      Knotting, aortic cross-clamp, cardiopulmonary bypass, and total operating room
      times were recorded. Hospital charges were also calculated for these procedures.
      RESULTS: Baseline characteristics, concomitant procedures, prosthetic valve size,
      and sutures were similar between groups. The titanium fastener group had
      significantly reduced knotting (7.4 vs. 13.0 minutes, P < 0.001), aortic cross
      clamp (69 vs. 90 minutes, P < 0.05), cardiopulmonary bypass (86 vs. 114 minutes,
      P < 0.05), and total operating room times (234 vs. 266 minutes, P < 0.05).
      Intraoperative complications occurred more frequently in the hand-tied group
      compared with the titanium fastener group. Postoperative complications were
      similar between groups. Operating room costs were significantly higher in the
      titanium fastener group (US $10,428 vs. US $9671, P = 0.01). Hospitalization
      costs did not differ significantly between the titanium fastener and hand-tied
      group (US $23,987 vs. US $21,068, P = 0.12). CONCLUSIONS: Titanium fastener use
      was associated with shorter knotting, aortic cross-clamp, cardiopulmonary bypass,
      and operating room times and fewer intraoperative complications in open aortic
      valve replacement, without significantly increasing hospitalization cost.

PMID- 29465630
TI  - Safety and Functionality of a Guidewire Fixator: Clinical Investigation of a New
      Endovascular Tool.
AB  - OBJECTIVE: A new endovascular tool, the Liungman Guidewire Fixator, has been
      developed to simplify endovascular treatment in complex aortic aneurysms. The
      device has been extensively tested in bench models and animal trials. To verify
      the safety and functionality demonstrated in the porcine model, the device was
      tested in ten patients undergoing endovascular aortic repair (EVAR) or
      fenestrated endovascular aortic repair (f-EVAR) treatment for abdominal aortic
      aneurysm. METHODS: The Liungman Guidewire Fixator consists of a braided stent
      like, cylindrical structure with conical ends and a central channel for a 0.035"
      guidewire. When in use, it is slid along the guidewire and positioned in the
      target artery, where the Liungman Guidewire Fixator interacts with the arterial
      wall by anchoring the guidewire to the wall through a radial force. The Liungman
      Guidewire Fixator allows for uninterrupted blood flow passed the point of
      fixation. In this study, the Liungman Guidewire Fixator was tested in ten
      patients undergoing EVAR or f-EVAR treatment for abdominal aortic aneurysm. The
      device was deployed and retrieved crossover into the hypogastric artery, and the
      occurrence of thrombotic occlusion, arterial dissection, and vascular rupture or
      trauma was studied using angiography, as well as device ability to withstand
      guidewire tension. RESULTS: There were no instances of occlusion, dissection, or
      vascular trauma detected using angiography. In all cases, deployment and
      retrieval were successful, and the devices could withstand an applied tension of
      3 N. In one instance, retrieval was challenging because of significant
      tortuosity, which was resolved by a coaxial catheterization. CONCLUSIONS:
      Deployment was uneventful in all ten patients. Retrieval according to the
      intended instruction for use was performed in nine of the patients. In one
      patient, a coaxial catheterization was necessary. All devices withstood a
      retention force of 3 N.

PMID- 29465631
TI  - Near-Infrared Cerebral Oximetry to Predict Outcome After Pediatric Cardiac
      Surgery: A Prospective Observational Study.
AB  - OBJECTIVES: To assess whether near-infrared cerebral tissue oxygen saturation,
      measured with the FORESIGHT cerebral oximeter (CAS Medical Systems, Branford, CT)
      predicts PICU length of stay, duration of invasive mechanical ventilation, and
      mortality in critically ill children after pediatric cardiac surgery. DESIGN:
      Single-center prospective, observational study. SETTING: Twelve-bed PICU of a
      tertiary academic hospital. PATIENTS: Critically ill children and infants with
      congenital heart disease, younger than 12 years old, admitted to the PICU between
      October 2012 and November 2015. Children were monitored with the FORESIGHT
      cerebral oximeter from PICU admission until they were weaned off mechanical
      ventilation. Clinicians were blinded to cerebral tissue oxygen saturation data.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was the
      predictive value of the first 24 hours of postoperative cerebral tissue oxygen
      saturation for duration of PICU stay (median [95% CI], 4 d [3-8 d]) and duration
      of mechanical ventilation (median [95% CI], 111.3 hr (69.3-190.4 hr]). We
      calculated predictors on the first 24 hours of cerebral tissue oxygen saturation
      monitoring. The association of each individual cerebral tissue oxygen saturation
      predictor and of a combination of predictors were assessed using univariable and
      multivariable bootstrap analyses, adjusting for age, weight, gender, Pediatric
      Index of Mortality 2, Risk Adjustment in Congenital Heart Surgery 1, cyanotic
      heart defect, and time prior to cerebral tissue oxygen saturation monitoring. The
      most important risk factors associated with worst outcomes were an increased SD
      of a smoothed cerebral tissue oxygen saturation signal and an elevated cerebral
      tissue oxygen saturation desaturation score. CONCLUSIONS: Increased SD of a
      smoothed cerebral tissue oxygen saturation signal and increased depth and
      duration of desaturation below the 50% saturation threshold were associated with
      longer PICU and hospital stays and with longer duration of mechanical ventilation
      after pediatric cardiac surgery.

PMID- 29465632
TI  - Advancing Research in Vision Science through Philanthropy.

PMID- 29465633
TI  - Reported Primary and Secondary Syphilis Cases in the United States: Implications
      for HIV Infection.
AB  - BACKGROUND: Recent increases in syphilis among men who have sex with men (MSM)
      are especially concerning, given the biologic and epidemiologic associations
      between syphilis and HIV infection. We sought to better describe the current
      epidemiology of primary and secondary (P&S) syphilis and the prevalence of HIV
      infection among reported P&S syphilis cases by demographic group, including sex
      of sex partner, in the United States in 2016. METHODS: We reviewed national P&S
      syphilis case report data from 2016, including available risk factor information
      such as sex of sex partner and HIV status. Data were extracted from the National
      Electronic Telecommunications System for Surveillance, the system through which
      Centers for Disease Control and Prevention receives notifiable sexually
      transmitted disease data from all 50 states and the District of Columbia. The
      proportion of cases with HIV coinfection was calculated using cases with known
      HIV status as the denominator. RESULTS: Of 27,814 P&S syphilis cases reported in
      2016, 58.1% were among MSM, 13.9% were among men who have sex with women only,
      11.0% were among women, and 16.9% were among men without data on sex of sex
      partners. Similar patterns were observed across geographic regions,
      race/ethnicity groups, and most age groups. Overall, 38.5% of reported P&S
      syphilis cases with known HIV status were coinfected with HIV. The prevalence of
      HIV coinfection was highest among MSM (47.0%) compared with men who have sex with
      women only (10.7%) or women (4.1%). Among MSM with P&S syphilis, the prevalence
      of HIV coinfection was highest among black MSM, ranging from 33.8% among black
      MSM aged 15 to 19 years to 77.8% among black MSM aged 45 to 49 years.
      CONCLUSIONS: These data underscore the epidemiologic linkages between syphilis
      and HIV, particularly among MSM. Primary and secondary syphilis may represent an
      opportunity to prevent HIV infection among persons who are HIV negative and
      identify and link to care persons living with HIV infection but not currently
      engaged in care.

PMID- 29465636
TI  - Optimizing the Impact of Expedited Partner Therapy.

PMID- 29465634
TI  - Prescription of Preexposure Prophylaxis to Men Who Have Sex With Men Diagnosed
      and Reported With Gonorrhea, STD Surveillance Network, 2016.
AB  - Using a representative sample of gonorrhea cases in select jurisdictions, we
      estimated the proportion of eligible men who have sex with men reporting being
      prescribed preexposure prophylaxis (PrEP) to prevent HIV infection. In 2016, half
      (51.3%) of the estimated 33,165 eligible men who have sex with men reported being
      prescribed PrEP by their health care provider.

PMID- 29465637
TI  - Considering the Potential Application of Whole Genome Sequencing to Gonorrhea
      Prevention and Control.

PMID- 29465639
TI  - Multi-state Syphilis Outbreak among American Indians, 2013-2015.
AB  - This article summarizes a multi-state outbreak of heterosexual syphilis,
      including 134 cases of syphilis in adults and adolescents and at least two cases
      of congenital syphilis, which occurred on an American Indian reservation in the
      United States during 2013-2015. In addition to providing salient details about
      the outbreak, the article seeks to document the case-finding and treatment
      activities undertaken, their relative success or failure, and the lessons learned
      from a coordinated, multiagency response. Of 134 adult cases of syphilis, 40%
      were identified by enhanced, interagency contact tracing and partner services;
      26% through symptomatic testing; and 16% through screening of asymptomatic
      individuals as the result of an electronic medical record (EMR) screening prompt.
      A smaller proportion of cases were identified by community screening events in
      high-morbidity communities; high risk venue-based screening events; other
      screening, including screening upon request; and prenatal screening at first
      trimester, third trimester, and day-of-delivery. Future heterosexual syphilis
      outbreak responders should act quickly to coordinate a package of high-yield case
      finding and treatment activities-potentially including activities that seek to do
      the following: 1) increase prenatal screening, 2) improve community awareness and
      symptomatic test-seeking, 3) educate providers and improve general screening for
      syphilis; 4) implement EMR reminders for providers; 5) screen high-morbidity
      communities and at high-risk venues; and 6) form novel partnerships to accomplish
      partner services work when the context does not allow for traditional, DIS-only
      partner services.

PMID- 29465638
TI  - Out of the Closet, Into the Clinic: Opportunities for Expanding Men Who Have Sex
      With Men-Competent Services in China.
AB  - BACKGROUND: Despite the high human immunodeficiency virus (HIV) burden among men
      who have sex with men (MSM), there is little research on health services provided
      to MSM in China and other low- and middle-income countries. Discrimination and
      inadequate services may discourage MSM from seeking health care services. This
      study examined essential services provided to MSM and health care discrimination
      among MSM in China. METHODS: A nationwide cross-sectional online survey was
      conducted among MSM who saw a physician in the last 24 months in China. The
      survey included items on sociodemographic information, HIV testing, experiences
      from the last physician encounter, and history of perceived health care
      discrimination. We defined MSM-competent physicians as physicians who asked their
      patient about having sex with other men, asked about anal sex, and either asked
      about or recommended HIV testing at the most recent visit. RESULTS: Among the 503
      participants, 35.0% (176/503) saw an MSM-competent physician. In multivariate
      analyses, respondents who saw an MSM-competent physician were more likely to be
      younger (adjusted odds ratio [AOR], 0.87; 95% confidence interval [CI], 0.81
      0.94), have a primary care physician (AOR, 3.24; 95% CI, 1.85-5.67), and be
      living with HIV (AOR, 2.01; 95% CI, 1.13-3.56). 61.2% (308/503) of MSM had ever
      experienced health care discrimination. CONCLUSIONS: Our data suggest that there
      is variability in the extent to which physicians are meeting the needs of MSM in
      China. There is an urgent need to evaluate and expand MSM-competent services in
      China.

PMID- 29465640
TI  - Context-Appropriate Interventions to Prevent Syphilis: A Narrative Review.
AB  - BACKGROUND: The success of an intervention to prevent syphilis will depend on the
      context and the goal of the intervention. To help programs choose interventions,
      we reviewed major changes in context and types of interventions that may be
      effective. METHODS: We reviewed the literature on the changing context of
      syphilis in the United States and interventions to prevent syphilis, focusing on
      articles that included evidence of effectiveness. RESULTS: Populations acquiring
      syphilis are constantly changing. Currently, incidence is very high among men who
      have sex with men (MSM). Among adults, late disease caused by syphilis has become
      rare. Congenital syphilis incidence has been low but is increasing, and morbidity
      and mortality remain high when babies are infected. Congenital syphilis now
      causes more deaths than syphilis among adults.Routine screening of MSM can
      identify and treat infections before they progress to disease (secondary
      prevention). Screening rates are highest when done as part of routine standing
      orders. Partner notification effectiveness has decreased, partly because many
      partners are anonymous. Most congenital syphilis can be prevented by screening
      pregnant women; it has been eliminated in areas where intense primary prevention
      efforts eliminated syphilis among women. CONCLUSIONS: So far, no program has
      stopped the increasing rates of infection among MSM, but secondary prevention
      efforts have prevented most disability. Congenital syphilis is increasing, and
      can be decreased by screening pregnant women and stopped by intensive efforts to
      prevent infection among women.

PMID- 29465641
TI  - Relative Impact of Different Strategies for Allocating Federal Funds for Syphilis
      Prevention.
AB  - BACKGROUND: Improvements in resource allocation can increase the benefits of
      federally funded sexually transmitted disease (STD) prevention activities. The
      purpose of this study was to illustrate how different strategies for allocating
      federal funds to subnational districts for syphilis prevention might affect the
      incidence of syphilis at the national level. METHODS: We modeled syphilis rates
      by district and year using an equation based on a previous analysis of state
      level syphilis elimination funding and syphilis case rates from 1998 to 2005 in
      the United States. We used the model to illustrate the potential impact of 3
      different strategies for allocating supplemental federal funds to subnational
      districts to support syphilis prevention activities a hypothetical country with
      18 subnational districts. The 3 strategies were based on each district's (1)
      population size, (2) syphilis incidence rate, or (3) number of syphilis cases.
      The hypothetical country was similar to the United States in overall population
      and syphilis burden. RESULTS: Without the supplemental federal funds, there would
      be an estimated 48,600 incident infections annually in the hypothetical country.
      With the supplemental federal funds, the annual number of infections would be
      reduced to 27,800 with a population-based allocation of funding to each district,
      26,700 with a rate-based allocation, and 24,400 with a case-based allocation of
      funding. CONCLUSIONS: Allocating federal STD prevention funds to districts based
      on burden of disease can be an efficient strategy, although this efficiency may
      be reduced or eliminated when high-burden districts have less ability to provide
      adequate STD prevention services than lower-burden districts.

PMID- 29465642
TI  - Spontaneous Clearance of Pharyngeal Gonococcal Infections: A Retrospective Study
      in Patients of the Sexually Transmitted Infections Clinic; Amsterdam, the
      Netherlands; 2012 to 2015.
AB  - INTRODUCTION: Pharyngeal Neisseria gonorrhoeae infections are mostly
      asymptomatic, yet sustain ongoing gonococcal transmission. We assessed the
      proportion of pharyngeal gonorrhea that spontaneously clears and identified
      determinants of clearance. METHODS: At the sexually transmitted infections clinic
      Amsterdam, at-risk women and men who have sex with men were routinely screened
      for pharyngeal N. gonorrhoeae using an RNA-based nucleic acid amplification test
      (NAAT; Aptima Combo 2).We retrospectively examined medical records of pharyngeal
      gonorrhea patients (January 2012-August 2015). We included patients who returned
      for antibiotic treatment and had a new sample taken for NAAT before treatment.
      Spontaneous clearance was defined as a negative NAAT result at the follow-up
      visit. RESULTS: During the study period, 1266 cases with a pharyngeal gonorrhea
      were not treated at the first consultation and returned for a follow-up visit.
      Median (interquartile range) time between the first consultation and follow-up
      was 10 (7-14) days. Spontaneous clearance was found in 139 cases (11.0%) and was
      associated with age at least 45 years (vs. 16-24 years; adjusted odds ratio, 2.02
      [95% confidence interval, 1.09-3.75]) and with time from the first consultation
      to follow-up (adjusted odds ratio, 1.08 [1.06-1.10], per extra day). CONCLUSIONS:
      Eleven percent of pharyngeal gonorrhea cases cleared spontaneously. Spontaneous
      clearance of pharyngeal gonorrhea was more often seen among older patients.

PMID- 29465643
TI  - Human Immunodeficiency Virus Partner Notification Services Among a Representative
      Sample of Young Black Men Who Have Sex With Men Demonstrates Limited Service
      Offering and Potential Benefits of Clinic Involvement.
AB  - BACKGROUND: Partner notification (PN) is commonly offered to persons recently
      diagnosed with human immunodeficiency virus (HIV) to improve linkage to care and
      prevent onward transmission. Yet, much remains unknown about the factors
      associated with successful PN participation in populations at highest risk.
      METHODS: Data were collected during the first 2 waves (2013-2015) of "uConnect,"
      a population-based cohort study of young black men who have sex with men in
      Chicago (N = 618). Participants completed a biobehavioral survey and were tested
      for HIV. Among HIV-infected participants (N = 187), weighted logistic regression
      models examined the relationship between participant characteristics and being
      offered PN and providing partner names. RESULTS: 30.3% (n = 187) of the sample
      was HIV-positive, of which 71.7% (n = 134) were offered PN, including: 8.2% (n =
      11) by the city health department; 51.5% (n = 69) by health care providers; and
      40.3% (n = 54) by both. Being offered PN was significantly associated with
      criminal justice involvement history (adjusted odds ratio [aOR], 2.49; 95%
      confidence interval [CI], 1.38-4.49), volatile nitrates usage (aOR, 2.88; 95% CI,
      1.20-6.94), and recent conversations with HIV outreach workers (aOR, 2.68; 95%
      CI, 1.25-5.77). Providing partner names was significantly associated with
      intermittent (aOR, 7.26; 95% CI, 1.75-30.07) and heavy (aOR, 11.47; 95% CI, 2.57
      51.22) marijuana use, and being offered PN by both the city health department and
      health care provider (aOR, 8.36; 95% CI, 2.73-25.62). CONCLUSIONS: A substantial
      proportion of HIV-diagnosed individuals were never offered PN. Being offered PN
      by multiple sources is associated with participation, and improved collaboration
      within health systems may improve participation rates.

PMID- 29465644
TI  - State laws related to billing third parties for healthcare services at public STD
      clinics in the United States.
AB  - BACKGROUND: Health departments (HDs) cite state laws as barriers to billing third
      parties for sexually transmitted disease (STD) services, but the association
      between legal/policy barriers and third party HD billing has not been examined.
      This study investigates the relationship between laws that may limit HDs' ability
      to bill, clinic perceptions of billing barriers, and billing practices. METHODS:
      Two surveys (1) clinic managers [N=246], 2) STD program managers [N=63])
      conducted via a multi-regional needs assessment of federally funded HD clinics'
      capacity to bill for STD services, billing/reimbursement practices, and perceived
      barriers were combined with an analysis of state laws regarding third party
      billing for STD services. Statistical analyses examined relationships between
      laws that may limit HDs' ability to bill, clinic perceptions, and billing
      practices. RESULTS: Clinic managers reported clinics were less likely to bill
      Medicaid and other third parties in jurisdictions with a state law limiting their
      ability to bill compared to respondents who billed neither or one payer (OR=0.31,
      CI=0.10,0.97) and cited practical concerns as a primary barrier to billing
      (OR=2.83 CI=1.50,5.37). STD program managers' reports that staff believed STD
      services should be free (OR=0.34, CI=0.13, 0.90) was associated with not billing
      (not sure versus no resistance to billing); confidentiality concerns was not a
      reported barrier to billing among either sample. CONCLUSIONS: Practical concerns
      and clinic staff beliefs that STD services should be free emerged as possible
      barriers to billing, and laws less so. Attempts to initiate HD billing for STD
      services may benefit from staff education as well as addressing perceived legal
      barriers and staff concerns.

PMID- 29465645
TI  - Assessing STD Partner Services in State and Local Health Departments.
AB  - State and local health department STD programs provide several partner services
      to reduce disease transmission. Budget cuts and temporary staff reassignments for
      public health emergencies may affect the provision of partner services.
      Determining the impact of staffing reductions on STD rates and public health
      response should be further assessed.

PMID- 29465646
TI  - New Human Immunodeficiency Virus Diagnoses Among Men Who Have Sex With Men
      Attending Sexually Transmitted Disease Clinics, STD Surveillance Network, January
      2010 to June 2013.
AB  - : To estimate new human immunodeficiency virus (HIV) diagnosis rates among HIV
      negative men who have sex with men (MSM) who are repeatedly tested for HIV in
      sexually transmitted disease (STD) clinics and assess the impact of demographic
      and disease-specific characteristics that are associated with higher HIV
      diagnosis rates. STUDY DESIGN: Retrospective analysis using 2010 to 2013 data
      from the STD Surveillance Network (SSuN), a sentinel surveillance system
      comprised of health departments in 12 cities conducting sentinel surveillance in
      40 STD clinics. We analyzed data from all MSM repeatedly (>=2 times) tested for
      HIV, with an initial negative HIV test required for staggered cohort entry.
      Follow-up time was accrued from the date of the first negative HIV test to the
      most recent negative test or the first positive HIV test. The STD diagnoses
      during the follow-up period were reviewed. We estimated HIV diagnoses rates
      (number of HIV diagnoses/total number of person-years [PY] at risk) by
      demographic and clinical characteristics with 95% confidence intervals (CI) using
      an inverse variance weighted random effects model, adjusting for heterogeneity
      between SSuN jurisdictions. RESULTS: Overall, 640 HIV diagnoses occurred among
      14,824 individuals and 20,951.6 PY of observation, for an adjusted incidence of
      HIV diagnosis of 3.0 per 100 PY (95% CI, 2.6-3.4). Rates varied across
      race/ethnicity groups with the highest rate among Blacks (4.7/100 PY; 95% CI, 4.1
      5.3) followed by Hispanics, whites, and persons of other races/ethnicities. Men
      who have sex with men having a diagnosis of primary or secondary (P&S) syphilis
      on or after the first negative HIV test had a higher new HIV diagnosis rate
      (7.2/100 PY; 95% CI, 5.8-9.0) compared with MSM who did not have a P&S syphilis
      diagnosis (2.8/100 PY; 95% CI, 2.6-3.1). Men who have sex with men who tested
      positive for rectal gonorrhea (6.3/100 PY; 95% CI, 5.7-6.9) or rectal chlamydia
      (5.6/100 PY; 95% CI, 4.6-6.6) had higher rates of new HIV diagnosis when compared
      to those with negative test results. CONCLUSIONS: Men who have sex with men
      attending SSuN STD clinics have high rates of new HIV diagnoses, particularly
      those with a previous diagnosis of P&S syphilis, rectal chlamydia, and/or
      gonorrhea. Sexually transmitted disease clinics continue to be important clinical
      setting for diagnosing HIV among MSM populations.

PMID- 29465647
TI  - Sexually Transmitted Infection Positivity Rate and Treatment Uptake Among Female
      and Male Sexual Assault Victims Attending The Amsterdam STI Clinic Between 2005
      and 2016.
AB  - BACKGROUND: Victims could become infected with sexually transmitted infections
      (STIs) during a sexual assault. Several guidelines recommend presumptive
      antimicrobial therapy for sexual assault victims (SAVs). We assessed the STI
      positivity rate and treatment uptake of female and male SAVs at the Amsterdam STI
      clinic. METHODS: Sexual assault victims answered assault-related questions and
      were tested for bacterial STI (chlamydia, gonorrhea, and syphilis), hepatitis B,
      and HIV during their initial visits. Sexual assault victim characteristics were
      compared with non-SAV clients. Backward multivariable logistic regression
      analysis was conducted to assess whether being an SAV was associated with a
      bacterial STI. The proportion of those returning for treatment was calculated.
      RESULTS: From January 2005 to September 2016, 1066 (0.6%) of 168,915 and 135
      (0.07%) of 196,184 consultations involved female and male SAVs, respectively.
      Among female SAVs, the STI positivity rate was 11.2% versus 11.6% among non-SAVs
      (P = 0.65). Among male SAVs, the STI positivity rate was 12.6% versus 17.7% among
      non-SAVs (P = 0.12). In multivariable analysis, female SAVs did not have
      increased odds for an STI (odds ratio 0.94; 95% confidence interval, 0.77-1.13),
      and male SAVs had significantly lower odds for an STI (odds ratio, 0.60; 95%
      confidence interval, 0.36-0.98). Of SAVs requiring treatment, 89.0% (female) and
      92.0% (male) returned. CONCLUSIONS: The STI positivity rate among female SAVs was
      comparable with female non-SAVs, but male SAVs had lower odds for having a
      bacterial STI than did male non-SAVs, when adjusting for confounders. The return
      rate of SAV for treatment was high and therefore does not support the
      recommendations for presumptive therapy.

PMID- 29465648
TI  - Associations Between Anorectal Chlamydia and Oroanal Sex or Saliva Use as a
      Lubricant for Anal Sex: A Cross-sectional Survey.
AB  - BACKGROUND: Receptive condomless anal sex is a known risk factor for anorectal
      chlamydia, but it remains unclear whether oroanal sex practices also contribute.
      We aimed to determine whether oroanal sex ("rimming"), fingering, or the use of
      saliva as anal lubricant are risk factors for anorectal chlamydia among men who
      have sex with men (MSM). METHODS: This cross-sectional study was conducted at
      Melbourne Sexual Health Centre from July 2014 to June 2015. Routinely collected
      computer-assisted self-interview data included demographics, number of sexual
      partners, and condom use. We added questions on receptive rimming, receptive
      fingering or penis "dipping," and the use of a partner's saliva as anal
      lubricant. RESULTS: A total of 1691 MSM completed the questionnaire and tested
      for anorectal chlamydia. In univariable analyses, anorectal chlamydia was
      associated with using a partner's saliva as lubricant (odds ratio [OR] 1.97, 95%
      confidence interval [CI] 1.26-3.09), receptive rimming (OR 1.59; 95% CI 1.04
      2.45), and receptive fingering or dipping (OR 1.90; 95% CI 1.06-3.43). In
      multivariable analysis, anorectal chlamydia was not associated with these sexual
      practices, after adjusting for number of sexual partners, HIV status, known
      contact with chlamydia, and condom use. However, collinearity between sexual
      practices likely obscured associations with anorectal chlamydia, and further
      analyses suggested weak associations between these sexual practices and anorectal
      chlamydia. CONCLUSIONS: The use of a partner's saliva during receptive anal sex
      practices such as rimming, fingering, or penis dipping were weak risk factor for
      anorectal chlamydia in MSM. This contrasts with our previously reported findings
      that the use of saliva as anal lubricant is more strongly associated with
      anorectal gonorrhea.

PMID- 29465649
TI  - Mycoplasma genitalium Infection in Kenyan and US Women.
AB  - BACKGROUND: Little is known about the natural history of Mycoplasma genitalium
      (MG) infection in women. We retrospectively tested archived vaginal fluid samples
      to assess MG prevalence, incidence, persistence, recurrence and antimicrobial
      resistance markers among women participating in the Preventing Vaginal Infections
      trial, a randomized trial of monthly presumptive treatment to reduce vaginal
      infections. METHODS: High-risk, nonpregnant, HIV-negative women aged 18 to 45
      years from Kenya and the United States were randomized to receive metronidazole
      750 mg + miconazole 200 mg intravaginal suppositories or placebo for 5
      consecutive nights each month for 12 months. Clinician-collected swabs containing
      cervicovaginal fluid were tested for MG using Hologic nucleic acid amplification
      testing at enrollment and every other month thereafter. Specimens that were MG+
      underwent additional testing for macrolide resistance-mediating mutations by DNA
      sequencing. RESULTS: Of 234 women enrolled, 221 had available specimens and 25
      (11.3%) had MG at enrollment. Among 196 women without MG at enrollment, there
      were 52 incident MG infections (incidence, 33.4 per 100 person-years). Smoking
      was independently associated with incident MG infection (adjusted hazard ratio,
      3.02; 95% confidence interval, 1.32-6.93), and age less than 25 years trended
      toward an association (adjusted hazard ratio, 1.70; 95% confidence interval, 0.95
      3.06). Median time to clearance of incident MG infections was 1.5 months
      (interquartile range, 1.4-3.0 months). Of the 120 MG+ specimens, 16 specimens
      from 15 different women were macrolide resistance-mediating mutation positive
      (13.3%), with no difference by country. CONCLUSIONS: M. genitalium infection is
      common among sexually active women in Kenya and the Southern United States. Given
      associations between MG and adverse reproductive health outcomes, this high
      burden of MG in reproductive-aged women could contribute to substantial
      morbidity.

PMID- 29465650
TI  - Chlamydia Prevalence Trends Among Women and Men Entering the National Job
      Training Program From 1990 Through 2012.
AB  - BACKGROUND: Evaluating chlamydia prevalence trends from sentinel surveillance is
      important for understanding population disease burden over time. However,
      prevalence trend estimates from surveillance data may be misleading if they do
      not account for changes in risk profiles of individuals who are screened (case
      mix) and changing performance of the screening tests used. METHODS: We analyzed
      chlamydia screening data from a sentinel surveillance population of 389,555 young
      women (1990-2012) and 303,699 young men (2003-2012) entering the US National Job
      Training Program. This period follows the introduction of national chlamydia
      screening programs designed to prevent transmission and reduce population disease
      burden. After ruling out bias due to case mix, we used an expectation
      maximization-based maximum likelihood approach to account for measurement error
      from changing screening tests, and generated minimally biased long-term chlamydia
      prevalence trend estimates among youth and young adults in this sentinel
      surveillance population. RESULTS: Adjusted chlamydia prevalence among women was
      high throughout the study period, but fell from 20% in 1990 to 12% in 2003, and
      remained between 12% and 14% through 2012. Adjusted prevalence among men was
      steady throughout the study period at approximately 7%. For both women and men,
      adjusted prevalence was highest among Black and American Indian youth and young
      adults, and in the Southern and Midwestern regions of the United States
      throughout the study period. CONCLUSIONS: Our minimally biased trend estimates
      provide support for an initial decrease in chlamydia prevalence among women soon
      after the introduction of national chlamydia screening programs. Constant
      chlamydia prevalence in more recent years suggests that screening may not be
      sufficient to further reduce chlamydia prevalence among high-risk youth and young
      adults.

PMID- 29465651
TI  - The Epidemiology of Syphilis in New York City: Historic Trends and the Current
      Outbreak Among Men Who Have Sex With Men, 2016.
AB  - BACKGROUND: Male primary and secondary (P&S) and early latent syphilis cases have
      increased markedly in New York City (NYC) after a historic nadir in 1998. The
      majority of cases are among men who have sex with men (MSM). We describe the
      epidemiology of syphilis among NYC males to provide a model of how 1 jurisdiction
      collects, analyzes, interprets, uses, and disseminates local data to guide
      programmatic activities directed at syphilis control. METHODS: We analyzed trends
      in reported infectious syphilis cases using routinely collected surveillance and
      case investigation data. Human immunodeficiency virus (HIV) coinfection status
      was ascertained by routine deterministic match between sexually transmitted
      infection and HIV surveillance registries, and self-report. We mapped diagnosing
      facilities to display the relative contribution of different public/private
      facilities. Characteristics of male syphilis cases diagnosed in public sexual
      health (SH) clinics were compared to those diagnosed elsewhere. RESULTS: During
      2012 to 2016, male P&S syphilis case rates increased 81%, from 24.8 to
      44.8/100,000 (1832 cases in 2016); the highest rates were among black non
      Hispanic men. Overall, 87.6% (902/1030) of interviewed men in 2016 disclosed 1 or
      more male partner. The HIV coinfection rates are high among MSM with P&S syphilis
      (43.4%; 394/907 in 2016), but appear to be decreasing (from 54.1% in 2012). Maps
      highlight SH clinics' contribution to diagnosing P&S syphilis cases among men of
      color. HIV coinfection rates were lower among men with P&S syphilis diagnosed in
      SH clinics than among those diagnosed elsewhere (34%, SH clinics vs 49%; other
      settings, P < 0.0001). CONCLUSIONS: Syphilis infections continue to increase
      among MSM in NYC. Novel interventions responsive to the drivers of the current
      outbreak are needed.

PMID- 29465652
TI  - Whose Responsibility Is It? Beliefs About Preventing HIV Transmission Among Men
      Who Have Sex With Men.
AB  - HIV-negative and HIV-positive men believed that they both are responsible for
      preventing HIV. Responsibility beliefs, however, did not always correspond with
      discussing HIV status or refraining from serodiscordant condomless anal sex.
      Discrepancies between individuals' HIV prevention responsibility beliefs and
      their sexual risk behaviors merit further examination, particularly in the
      preexposure prophylaxis era.

PMID- 29465653
TI  - Clinical Characteristics of Anorectal Mycoplasma genitalium Infection and
      Microbial Cure in Men Who Have Sex With Men.
AB  - BACKGROUND: We report clinical characteristics of proctitis caused solely by
      Mycoplasma genitalium (MG) compared with chlamydia and gonococcus. We determined
      the proportions cured with first-line (azithromycin) and second-line
      antimicrobials (moxifloxacin, pristinamycin). METHODS: A total of 166 patients
      attending Melbourne Sexual Health Centre from 2012 to 2016 with symptoms of
      proctitis were tested for MG, Chlamydia trachomatis, and Neisseria gonorrhoeae.
      Demographic characteristics, sexual behaviors, clinical symptoms, and signs were
      recorded. Multinomial multivariable logistic regression was used to test for
      significant differences in symptoms and signs for the pathogens detected.
      RESULTS: Seventeen percent of men had MG (95% confidence interval, 12-24), 21%
      had chlamydia (15-27), and 40% had gonococcal monoinfection (32-48), whereas 22%
      had MG coinfection (16-29). Relative to men with MG monoinfection, those with
      chlamydial monoinfection reported more anal pain (adjusted prevalence odds ratio
      (aPOR), 4.68 [1.41-14.19]), whereas men with gonococcal monoinfection reported
      more anal pain (aPOR, 6.75 [2.21-20.55]) and tenesmus (aPOR, 15.44 [1.62
      146.90]), but less anal itch (aPOR, 0.32 [0.11-0.93]). The microbiological cure
      for MG using azithromycin was low at 35% (22-50), whereas moxifloxacin
      subsequently cured 92% (64-100) and pristinamycin cured 79% (54-94) of
      infections. CONCLUSIONS: M. genitalium was almost as common as chlamydia in men
      presenting to a sexual health center with symptoms of proctitis. Men with
      anorectal MG monoinfection were less likely to have symptoms and signs compared
      with those with chlamydia or gonococcus monoinfection. Cure for men with
      symptomatic anorectal MG by azithromycin was low. We suggest routine testing for
      MG in cases of proctitis, with test of cure after treatment being essential.

PMID- 29465654
TI  - HIV Co-infection among Persons Diagnosed with Sexually Transmitted Diseases, San
      Francisco, 2007-2014.
AB  - BACKGROUND: Early syphilis, gonorrhea, and chlamydia but not HIV infections have
      increased in San Francisco, primarily among men. METHODS: We linked records of
      persons reported with early syphilis, gonorrhea, and chlamydia to records of
      persons reported with HIV to measure the proportion and characteristics of San
      Francisco residents with HIV-STD co-infection between 2007 and 2014. We measured
      trends in HIV co-infection separately for men and women for each STD. RESULTS:
      From 2007 through 2014, 5,745 early syphilis, 18,037 gonorrhea, and 37,224
      chlamydia diagnoses were reported, 66%, 28%, and 15%, respectively, were among
      persons co-infected with HIV. Men accounted for the majority of persons with
      early syphilis, gonorrhea, and chlamydia HIV co-infection. For early syphilis and
      HIV co-infection, among MSM, Latinos were more likely and Asian/Pacific Islanders
      were less likely to have HIV co-infection compared to Whites. Older age at
      diagnosis and prior history of a STD were both also significantly associated with
      early syphilis and HIV co-infection. Transgender persons, older ages, Latino MSM
      compared to White MSM and those with a prior history of STD were more likely to
      have HIV co-infection whereas Asian/Pacific Islander MSM were less likely to have
      HIV co-infection for both gonorrhea and chlamydia. CONCLUSIONS: Our findings
      highlight the high burden of HIV-STD co-infection in San Francisco. To maintain
      the current declines in HIV incidence and turn the curve in rising STD incidence,
      there is an urgent need for collaborative HIV and STD prevention and control
      efforts.

PMID- 29465655
TI  - Defining the Urethritis Syndrome in Men Using Patient Reported Symptoms.
AB  - To evaluate self-reported symptoms to guide urethritis diagnosis, symptomatic men
      being evaluated for urethritis were asked about 7 symptoms captured during
      history taking. Discharge and dysuria were significantly associated with
      urethritis and, when combined with genital irritation and itching, identified 95%
      of urethritis cases; odor and urinary frequency performed poorly.

PMID- 29465656
TI  - Herpes Simplex Virus Type 2 Seroprevalence Among Different National Populations
      of Middle East and North African Men.
AB  - BACKGROUND: There are limited data on herpes simplex virus type 2 (HSV-2)
      seroprevalence in the Middle East and North Africa (MENA). We examined country-
      and age-specific HSV-2 seroprevalence among select MENA populations residing in
      Qatar. METHODS: Sera were collected from male blood donors attending Hamad
      Medical Corporation between June 2013 and June 2016. Specimens were screened for
      anti-HSV-2 IgG antibodies following a 2-test algorithm: HerpeSelect 2 ELISA was
      used to identify HSV-2-positive specimens, and Euroline-WB was used to confirm
      positive and equivocal specimens for final HSV-2 status. Trends and associations
      with HSV-2 seropositivity were assessed. RESULTS: Of the 2077 tested sera, 61
      were found and confirmed positive. The proportion of those confirmed positive
      increased steadily with HerpeSelect 2 ELISA index value, ranging from 16.3% for
      index values of 1.101 to 1.999 to 92.9% for index values of 4 or greater.
      Nationality-specific seroprevalence was 6.0% (95% confidence interval [CI], 4.1%
      8.8%) in Qataris, 5.3% (95% CI, 2.5%-11.1%) in Iranians, 4.2% (95% CI, 1.8%-9.5%)
      in Lebanese, 3.1% (95% CI, 1.2%-7.7%) in Sudanese, 3.0% (95% CI, 1.4%-6.4%) in
      Palestinians, 2.2% (95% CI, 1.1%-4.3%) in Egyptians, 2.0% (95% CI, 1.0%-5.0%) in
      Syrians, 1.0% (95% CI, 0.3%-3.6%) in Jordanians, 0.7% (95% CI, 0.1%-3.7%) in
      Yemenis, and 0.5% (95% CI, 0.1%-2.8%) in Pakistanis. There was evidence for
      higher seroprevalence in older age groups. CONCLUSIONS: The seroprevalence of HSV
      2 was in the range of few percentage points. There were no major differences in
      seroprevalence by nationality. These findings add to our understanding of HSV-2
      epidemiology in MENA and indicate unmet needs for sexual health and control of
      sexually transmitted infections.

PMID- 29465658
TI  - Pathways to Congenital Syphilis Prevention: A Rapid Qualitative Assessment of
      Barriers, and the Public Health Response, in Caddo Parish, Louisiana.
AB  - BACKGROUND: Congenital syphilis (CS) disproportionately affects racial and ethnic
      minority women, especially in the US South. Although CS is relatively easy and
      inexpensive to prevent through screening and treatment of pregnant women, CS
      cases have continued to rise and are concentrated in relatively few US counties
      and states. In 2010, Louisiana had the highest case rate in the country for
      primary, secondary, and CS, with the highest number of CS cases in northwest
      Louisiana, where Shreveport is located. METHODS: We conducted qualitative
      interviews with community members (women and frontline providers) living in Caddo
      Parish to obtain their views about factors that negatively impact CS prevention.
      RESULTS: Participants described impediments in the pathways for prevention of CS.
      Lack of sexual and reproductive health education, discontinuities and
      fragmentation in health care insurance coverage, a dearth of referral points for
      prenatal care, and difficulty finding prenatal care providers who accept Medicaid
      can delay timely and adequate care for pregnant women. Participants reported that
      low reimbursement for necessary injections and difficulty obtaining required
      medication challenged efforts to screen and treat pregnant women according to
      guidelines. CONCLUSIONS: Although CS is easily prevented, health system and
      policy obstacles in pathways to CS prevention and care may need remediation at
      state and local levels.

PMID- 29465659
TI  - Self-Reported Chlamydia and Gonorrhea Testing and Diagnosis Among Men Who Have
      Sex With Men-20 US Cities, 2011 and 2014.
AB  - BACKGROUND: Annual screening for chlamydia and gonorrhea is recommended for
      sexually active men who have sex with men (MSM) at anatomical sites of contact,
      regardless of condom use. METHODS: We assessed differences in self-reported
      chlamydia and gonorrhea testing and diagnosis in the past 12 months among MSM
      using National HIV Behavioral Surveillance data from 2011 and 2014. Men who have
      sex with men who had 1 or more partners in the past 12 months were included in
      analyses. Analyses of chlamydia and gonorrhea diagnosis data were limited to
      participants who reported past 12 months chlamydia and gonorrhea testing,
      respectively. Differences in testing and diagnosis over time were assessed using
      Poisson regression models with robust standard errors separately for chlamydia
      and gonorrhea. RESULTS: Analyses included data from 18,896 MSM (2011, n = 9256;
      2014, n = 9640). Testing for chlamydia was 37% in 2011 and 47% in 2014
      (prevalence ratio [PR], 1.25; 95% confidence interval [CI], 1.20-1.30) and 38%
      and 47% for gonorrhea (PR, 1.24; 95% CI, 1.19-1.29). Testing was higher in 2014
      among most demographic subgroups. Prevalence of chlamydia diagnoses was 8% in
      2011 and 11% in 2014 (PR, 1.37; 95% CI, 1.18-1.59) and of gonorrhea diagnoses was
      10% in 2011 and 14% in 2014 (adjusted PR: 1.40, 95% CI, 1.23-1.60). Larger
      changes in diagnoses were observed among MSM in the white and "other" racial
      categories and those who disclosed same-sex behavior to their health care
      provider. CONCLUSIONS: Self-reported testing and diagnoses among MSM increased
      from 2011 to 2014. Increased efforts are needed to meet annual sexually
      transmitted disease screening recommendations among MSM at high HIV risk.

PMID- 29465660
TI  - Observed Treatment Responses to Short-Course Doxycycline Therapy for Rectal
      Lymphogranuloma Venereum in Men Who Have Sex With Men.
AB  - BACKGROUND: Lymphogranuloma venereum (LGV) has reestablished itself as an endemic
      sexually transmitted infection in the United Kingdom and elsewhere in Europe and
      North America over the last decade. Current guidelines suggest treatment with 21
      days of doxycycline; however, the evidence base for LGV treatment including its
      duration is very limited. METHODS: We conducted a retrospective review in 2
      central London genitourinary medicine clinics of men who have sex with men (MSM)
      with LGV in whom less than 21 days of doxycycline was used initially. RESULTS:
      Sixty MSM were treated initially with less than 21 days of doxycycline, of whom
      50 (83%) were prescribed a 7-day course. Fifty percent of patients were
      asymptomatic, with the rest having rectal or other symptoms. Fifty-nine (97%) of
      60 had a negative test of cure for LGV at a median of 31 days (7-200 days).
      Reinfection as opposed to treatment failure was considered likely in the patient
      testing positive. A second test of cure at a median of 139 days later (37-638
      days) was completed in 30 patients, of whom 28 (93%) were negative for LGV.
      CONCLUSIONS: Seven to 14 days of doxycycline is effective in most cases of LGV
      with negative TOCs in 59 of 60 patients. These data suggest that 7 days of
      doxycycline is effective in achieving cure of rectal LGV in most MSM. There is a
      case for a randomized controlled trial of LGV treatment including a 7-day regimen
      of doxycycline.

PMID- 29465661
TI  - Sexually Transmitted Infection Prevalence among Homeless Adults in the United
      States: A Systematic Literature Review.
AB  - BACKGROUND: Homelessness significantly affects health and well-being. Homeless
      adults often experience co-occurring and debilitating physical, psychological,
      and social conditions. These determinants are associated with disproportionate
      rates of infectious disease among homeless adults, including tuberculosis, HIV,
      and hepatitis. Less is known about sexually transmitted infection (STI)
      prevalence among homeless adults. METHODS: We systematically searched 3 databases
      and reviewed the 2000-2016 literature on STI prevalence among homeless adults in
      the United States. We found 59 articles of US studies on STIs that included
      homeless adults. Of the 59 articles, 8 met the inclusion criteria of US-based,
      English-language, peer-reviewed articles, published in 2000 to 2016, with
      homeless adults in the sample. Descriptive and qualitative analyses were used to
      report STI prevalence rates and associated risk factors. RESULTS: Overall, STI
      prevalence ranged from 2.1% to 52.5%. A composite STI prevalence was most often
      reported (n = 7), with rates ranging from 7.3% to 39.9%. Reported prevalence of
      chlamydia/gonorrhea (7.8%) was highest among younger homeless adult women.
      Highest reported prevalence was hepatitis C (52.5%) among older homeless men.
      Intimate partner violence, injection and noninjection substance use,
      incarceration history, and homelessness severity are associated with higher STI
      prevalence. CONCLUSIONS: Homeless adults are a vulnerable population. Factors
      found to be associated with sexual risk were concurrently associated with housing
      instability and homelessness severity. Addressing STI prevention needs of
      homeless adults can be enhanced by integrating sexual health, and other health
      services where homeless adults seek or receive housing and other support
      services.

PMID- 29465662
TI  - Social Vulnerability in Congenital Syphilis Case Mothers: Qualitative Assessment
      of Cases in Indiana, 2014 to 2016.
AB  - BACKGROUND: Congenital syphilis occurs when a pregnant woman with syphilis is not
      diagnosed or treated and the infection is passed in utero, causing severe infant
      morbidity and mortality. Congenital syphilis is easily prevented if women receive
      timely and adequate prenatal care. Cases of congenital syphilis are considered
      indicators of problems in the safety net. However, maternal social and behavioral
      factors can impede women's care, even when providers follow guidelines. METHODS:
      We reviewed case interviews and maternal records for 23 congenital syphilis cases
      reported to the Centers for Disease Control and Prevention from Indiana between
      2014 and 2016. We used qualitative methods to analyze narrative notes from
      maternal interviews to learn more about factors that potentially contributed to
      congenital syphilis cases. RESULTS: All providers followed Centers for Disease
      Control and Prevention and state recommendations for screening and treatment for
      pregnant women with syphilis. Twenty-one of 23 women had health insurance. The
      number of prenatal care visits women had was suboptimal; more than one third of
      women had no prenatal care. Nearly one third of women's only risk factor was sex
      with a primary male sex partner. The majority of women suffered social
      vulnerabilities, including homelessness, substance abuse, and incarceration.
      CONCLUSIONS: Despite provider adherence to guidelines and health insurance
      availability, some pregnant women with syphilis are unlikely to receive timely
      diagnosis and treatment. Pregnant women at high risk for syphilis may need
      additional social and material support to prevent a congenital syphilis case.
      Additional efforts are needed to reach the male partners of vulnerable females
      with syphilis.

PMID- 29465664
TI  - Knowledge, Practices, and Barriers to HIV Preexposure Prophylaxis Prescribing
      Among Washington State Medical Providers.
AB  - BACKGROUND: We aimed to assess HIV preexposure prophylaxis (PrEP) awareness and
      prescribing practices among Washington State medical providers from diverse
      professional disciplines and practice types. METHODS: In May 2016, we
      administered an anonymous online survey to licensed medical practitioners who
      provide primary, longitudinal, walk-in, emergency, obstetric, gynecologic,
      sexually transmitted infection, or family planning care. RESULTS: Of 735 eligible
      providers, 64.8% had heard of PrEP. Younger providers and providers with a doctor
      of medicine degree were more likely to be aware of PrEP compared with older
      providers (P = 0.0001) and providers of other training backgrounds (advanced
      registered nurse practitioner, doctor of osteopathic medicine, or physician
      assistant; P = 0.04). Among providers aware of PrEP, most frequent reported
      concerns about prescribing were adherence (46.0%) and costs (42.9%). Providers
      felt very (20.1%) or somewhat (33.8%) comfortable discussing PrEP overall, but
      very (26.8%) or somewhat (44.7%) uncomfortable discussing cost and insurance
      issues. The 124 PrEP prescribers reported a median of 2 (range, 1-175; total,
      1142) patients prescribed PrEP. Prior authorizations and insurance denials had
      prevented prescriptions for 28.7% and 12.1% of prescribers, respectively.
      CONCLUSIONS: Interventions to improve PrEP access should include education to
      inform medical providers about PrEP, with particular attention to provider types
      less likely to be aware. Continued efforts to eliminate cost and insurance
      barriers and educate providers regarding financial resources would help improve
      PrEP access.

PMID- 29465663
TI  - A Network Analysis of Sexually Transmitted Diseases and Online Hookup Sites Among
      Men Who Have Sex With Men.
AB  - BACKGROUND: Sexually transmitted diseases (STDs) are increasing among gay,
      bisexual, and other men who have sex with men (MSM). Little is known about the
      use of websites and mobile phone applications to meet sexual partners ("hookup
      sites") and association with STD diagnoses. METHODS: We performed a demographic
      and behavioral assessment of 415 MSM presenting to the Rhode Island STD clinic.
      Bivariate and multivariable analyses assessed associations between using hookup
      sites and testing positive for syphilis, gonorrhea, or chlamydia. Venue-based
      affiliation networks were created to evaluate hookup sites and their association
      with STD diagnoses. RESULTS: Among 415 MSM, 78% reported meeting a partner online
      in the last 12 months, and 25% tested positive for at least one STD. Men who met
      partners online were more likely to be white (67% vs. 54%, P = 0.03) and have
      more than 10 lifetime partners (87% vs. 58%, P < 0.05). The most commonly used
      hookup sites included Grindr (78%), Scruff (35%), and Tinder (22%). In the
      multivariable analysis, only Scruff use was associated with testing positive for
      an STD (odds ratio, 2.28; 95% confidence interval, 1.09-4.94). However, among men
      who met partners online, 75% of men diagnosed as having an STD had met a sexual
      partner on Grindr, including 100% of those who were diagnosed as having
      gonorrhea. CONCLUSIONS: Use of hookup sites was nearly ubiquitous among MSM
      undergoing STD screening. Specific hookup sites were significantly associated
      with STD diagnoses among MSM. Greater efforts are needed to promote STD screening
      and prevention among MSM who meet partners online.

PMID- 29465665
TI  - Syphilis Is (Still) Here: How Must Sexually Transmitted Disease Public Health
      Programs Adapt?

PMID- 29465666
TI  - Characteristics Associated With Delivery of an Infant With Congenital Syphilis
      and Missed Opportunities for Prevention-California, 2012 to 2014.
AB  - BACKGROUND: Congenital syphilis (CS), the transmission of Treponema pallidum from
      mother to fetus during pregnancy, can cause adverse birth outcomes. In 2012 to
      2014, the CS rate in California increased more than 200% from 6.6 to 20.3 cases
      per 100,000 live births. Our objectives were to identify characteristics
      associated with delivering an infant with CS and missed opportunities for
      prevention among syphilis-infected pregnant women in California. METHODS: We
      linked California Department of Public Health syphilis surveillance records from
      women aged 15 to 45 years-diagnosed from March 13, 2012, to December 31, 2014-to
      birth records. We compared characteristics among mothers who delivered an infant
      with CS (CS mothers) with mothers who delivered an infant without CS (non-CS
      mothers) by using chi or Fisher exact tests. To visualize gaps in prevention
      among syphilis-infected pregnant women, we constructed a CS prevention cascade, a
      figure that shows steps to prevent CS. RESULTS: During the selected period, 2498
      women were diagnosed as having syphilis, and 427 (17%) linked to birth records;
      164 (38%) were defined as CS mothers and 263 (62%) as non-CS mothers. Mothers
      with CS were more likely than non-CS mothers to have their first prenatal care
      visit in the third trimester. High proportions of mothers in both groups reported
      high-risk sexual behaviors, methamphetamine use, or incarceration (13%-29%). The
      CS prevention cascade showed decrements of 5% to 11% in prenatal care receipt,
      testing, and treatment steps; only 62% of potential CS births were prevented.
      CONCLUSIONS: Multifaceted efforts are needed to address gaps in the CS prevention
      cascade and reduce CS cases in California.

PMID- 29465667
TI  - Prospective Evaluation of Cervicovaginal Self- and Cervical Physician Collection
      for the Detection of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas
      vaginalis, and Mycoplasma genitalium Infections.
AB  - BACKGROUND: This study aimed to examine the agreement between sexually
      transmitted infection (STI) screening using self-collected specimens and
      physician-collected specimens, and to investigate the acceptability of self
      collection for screening in an 18-month study of female sex workers in a high
      risk, low-resource setting. METHODS: A total of 350 female sex workers in
      Nairobi, Kenya, participated in a prospective study from 2009 to 2011. Women self
      collected a cervicovaginal specimen. Next, a physician conducted a pelvic
      examination to obtain a cervical specimen. Physician- and self-collected
      specimens were tested for Chlamydia trachomatis, Neisseria gonorrhoeae,
      Trichomonas vaginalis, and Mycoplasma genitalium (MG) using Aptima nucleic acid
      amplification assays (Hologic). Specimens were collected at 3-month intervals
      over 18-month follow-up. kappa Statistics measured agreement of positivity
      between self-collection and physician collection. RESULTS: Baseline STI
      prevalence was 2.9% for N. gonorrhoeae, 5.2% for C. trachomatis, 9.2% for T.
      vaginalis, and 20.1% for MG in self-collected samples, and 2.3%, 3.7%, 7.2%, and
      12.9%, respectively, in physician-collected samples. kappa Agreement was
      consistently strong (range, 0.66-1.00) for all STIs over the 18-month study
      period, except for MG, which had moderate agreement (range, 0.50-0.75). Most
      participants found self-collection easy (94%) and comfortable (89%) at baseline,
      with responses becoming modestly more favorable over time. CONCLUSIONS: Self
      collected specimen screening results showed strong agreement to clinical
      collected specimens, except for MG, which was consistently detected more commonly
      in self-collected than in physician-collected specimens. Acceptability of the
      self-collection procedure was high at baseline and increased modestly over time.
      In high-risk, low-resource settings, STI screening with self-collected specimens
      provides a reliable and acceptable alternative to screening with physician
      collected specimens.

PMID- 29465668
TI  - Evaluation of the Implementation of a New Nurse-Led Express "Test-And-Go" Human
      Immunodeficiency Virus/Sexually Transmitted Infection Testing Service for Men Who
      Have Sex With Men at a Sexual Health Center in Melbourne, Australia.
AB  - BACKGROUND: In August 2015, a nurse-led express human immunodeficiency virus
      (HIV)/sexually transmitted infection (STI) testing service "Test-And-Go" (TAG)
      for asymptomatic men who have sex with men (MSM) was implemented in a large
      public sexual health center in Melbourne, Australia. We aimed to compare the
      clients' characteristics between the TAG and routine walk-in service among
      asymptomatic MSM. METHODS: This study was conducted at the Melbourne Sexual
      Health Centre, Australia, between August 5, 2015, and June 1, 2016. General
      estimating equation logistic regression models were constructed to examine the
      association between the use of TAG service and clients' demographic
      characteristics, sexual behaviors, and HIV/STI positivity. Clients' consultation
      and waiting times for both services were calculated. RESULTS: Of the 3520
      consultations, 784 (22.3%) were TAG services and 2736 (77.7%) were routine walk
      in services for asymptomatic MSM. Asymptomatic MSM were more likely to use the
      TAG service if they were born in Australia (adjusted odds ratio, 1.29; 95%
      confidence interval, 1.07-1.56), and had more than 6 male partners in the last 12
      months (adjusted odds ratio, 1.13; 95% confidence interval, 1.08-1.58). Age, HIV
      status, condomless anal sex and HIV/STI positivity did not differ between the two
      services. The TAG service had a shorter median waiting time (8.4 minutes vs 52.9
      minutes; p < 0.001) and consultation time (8.9 minutes vs 17.6 minutes; p <
      0.001) than the routine walk-in service. CONCLUSIONS: Although country of birth
      and sexual behaviors differed between clients attending the 2 services, there
      were no differences in HIV and STI positivity. Importantly, the TAG service
      required less waiting and consultation time and hence created additional clinic
      capacity at the general clinic to see clients who are at higher risk.

PMID- 29465669
TI  - Syphilis Control in the Post-Elimination Era: Implications of a New Syphilis
      Control Initiative for STD/HIV Programs.

PMID- 29465670
TI  - Effect of a Rapid Test Algorithm on Linkage to Medical Care and Viral Suppression
      Among New Jersey Residents, 2007 to 2015.
AB  - BACKGROUND: Efforts to identify and link human immunodeficiency virus-infected
      persons to medical care are the first steps to achieving viral suppression. In
      the United States, the goals are to link 85% of newly diagnosed persons to
      medical care in 30 days or less and for 80% to become virally suppressed by 2020.
      Among newly diagnosed residents from 2007 to 2015, in New Jersey, we evaluated
      the impact of a rapid testing algorithm (RTA) on linkage to medical care and
      viral suppression. METHODS: This is a retrospective review of data from New
      Jersey's Enhanced HIV/AIDS Reporting System for residents, newly diagnosed at 13
      years or older, from 2007 to 2015. We used survival analysis methods to estimate
      the proportion of residents and time to linkage to medical care and viral
      suppression. RESULTS: Of 8508 newly diagnosed residents, 60.3% and 72.3% were
      linked to medical care in 30 days or less and 90 days or less, respectively;
      45.7% achieved viral suppression in 365 days or less. Linkage to medical care in
      90 days or less and viral suppression in 365 days or less were more likely among
      those tested by RTA than laboratory testing. The adjusted hazard ratios for
      linkage to medical care, in clinical sites were 1.41, (95% confidence interval
      [CI], 1.22-1.63 and 1.08, 95% CI, 0.97-1.2 in community sites. The adjusted
      hazard ratios for viral suppression in clinical sites were 1.25 (95% CI, 1.05
      1.47 and 1.16, 95% CI, 1.01-1.32, in community sites. CONCLUSIONS: Implementation
      of a RTA may eliminate barriers to linkage to medical care and viral suppression
      leading to decreased morbidity, mortality, and transmission.

PMID- 29465671
TI  - Higher Levels of a Cytotoxic Protein, Vaginolysin, in Lactobacillus-Deficient
      Community State Types at the Vaginal Mucosa.
AB  - Vaginolysin (VLY), a cytotoxic protein produced by Gardnerella vaginalis, may
      contribute to bacterial vaginosis. We observed that women with G. vaginalis, low
      levels of lactobacilli, history of vaginal douching, higher Nugent scores, and
      higher vaginal pH had increased VLY. Inflammatory markers were not highly
      expressed with increasing VLY. Vaginolysin's role in bacterial vaginosis warrants
      further evaluation.

PMID- 29465673
TI  - Health Care Provider Perceptions of a Sexually Transmitted Infection Self-testing
      Program in an HIV Care Clinic.
AB  - BACKGROUND: Sexually transmitted infections (STIs) disproportionately affect men
      who have sex with men. Although clinical practice guidelines recommend routine
      STI screening of men who have sex with men who have high-risk behaviors,
      extragenital STI testing rates have been low in HIV clinics across the nation.
      The University of Washington STD Prevention Training Center implemented an STI
      self-testing program at a large HIV primary care clinic in Seattle, WA, to
      facilitate extragenital STI testing. METHODS: We performed a mixed-methods
      program evaluation to assess health care provider acceptability of the program at
      9 months after implementation. Twenty-eight clinicians were invited to complete
      an online survey. We conducted one-on-one, semistructured interviews with 6
      clinicians and a focus group with 7 members of the clinic nursing staff. Survey
      responses were tallied. Conventional content analysis was performed on survey
      comments and transcripts from the interviews and focus group. RESULTS: Ninety-one
      percent of clinicians were either satisfied or very satisfied with the program.
      Perceived advantages of the program included saving time for clinicians,
      overcoming patient discomfort, and increasing patient access to testing.
      Perceived program disadvantages included unclear responsibility of directing
      patients through the self-testing process and incorrect sample collection and
      labeling. CONCLUSIONS: Despite perceived disadvantages, the self-testing program
      was acceptable to clinicians and nursing staff, key population for successful
      program adoption. Implementation of STI self-testing programs in clinic settings
      could help to increase extragenital STI testing rates by removing provider and
      patient barriers to testing.

PMID- 29465674
TI  - The Etiology of Vaginal Discharge Syndrome in Zimbabwe: Results from the Zimbabwe
      STI Etiology Study.
AB  - INTRODUCTION: Symptomatic vaginal discharge is a common gynecological condition
      managed syndromically in most developing countries. In Zimbabwe, women presenting
      with symptomatic vaginal discharge are treated with empirical regimens that
      commonly cover both sexually transmitted infections (STIs) and reproductive tract
      infections, typically including a combination of an intramuscular injection of
      kanamycin, and oral doxycycline and metronidazole regimens. This study was
      conducted to determine the current etiology of symptomatic vaginal discharge and
      assess adequacy of current syndromic management guidelines. METHODS: We enrolled
      200 women with symptomatic vaginal discharge presenting at 6 STI clinics in
      Zimbabwe. Microscopy was used to detect bacterial vaginosis and yeast infection.
      Nucleic acid amplifications tests were used to detect Neisseria gonorrhoeae,
      Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium. In
      addition, serologic testing was performed to detect human immunodeficiency virus
      (HIV) infection. RESULTS: Of the 200 women, 146 (73%) had an etiology detected,
      including bacterial vaginosis (24.7%); N. gonorrhoeae (24.0%); yeast infection
      (20.7%); T. vaginalis (19.0%); C. trachomatis (14.0%) and M. genitalium (7.0%).
      Among women with STIs (N = 90), 62 (68.9%) had a single infection, 18 (20.0%) had
      a dual infection, and 10 (11.1%) had 3 infections.Of 158 women who consented to
      HIV testing, 64 (40.5%) were HIV infected.The syndromic management regimen
      covered 115 (57.5%) of the women in the sample who had gonorrhea, chlamydia, M.
      genitalium, or bacterial vaginosis, whereas 85 (42.5%) of women were treated
      without such diagnosis. CONCLUSIONS: Among women presenting with symptomatic
      vaginal discharge, bacterial vaginosis was the most common etiology, and
      gonorrhea was the most frequently detected STI. The current syndromic management
      algorithm is suboptimal for coverage of women presenting with symptomatic vaginal
      discharge; addition of point of care testing could compliment the effectiveness
      of the syndromic approach.

PMID- 29465675
TI  - App-Based Sexual Partner Seeking and Sexually Transmitted Infection Outcomes: A
      Cross-Sectional Study of HIV-Negative Men Who Have Sex With Men Attending a
      Sexually Transmitted Infection Clinic in Los Angeles, California.
AB  - BACKGROUND: Gay, bisexual, and other men who have sex with men (MSM) face higher
      rates of sexually transmitted infections (STIs) compared with the general
      population. The association between venues where sexual partners are met and STI
      transmission is dynamic and poorly understood, especially among those who use
      geosocial networking (GSN) apps. This study aimed to determine whether there is a
      difference in STI incidence between MSM who met their last sexual partner through
      a GSN app and MSM who met their last partner via other venues. METHODS: Data were
      analyzed from HIV-negative MSM attending the Los Angeles LBGT Center between
      August 2015 and July 2016 (n = 9499). Logistic regression models were used to
      investigate the relationship between STI incidence and whether or not an
      individual met his last partner through a GSN app. RESULTS: No relationship was
      detected between STI incidence and whether one's last sexual partner was met via
      GSN app. However, an association was detected between STI incidence and having
      used GSN apps to meet sexual partners in the past 3 months. A dose-response
      relationship was observed between the number of venues used to meet partners and
      testing positive for any STI (adjusted odds ratio, 1.08; 95% confidence interval,
      1.02-1.14). CONCLUSIONS: The relationship between how people meet sexual partners
      and STI acquisition is much more nuanced than previously thought. Geosocial
      networking apps do not inherently expose users to high-risk reservoirs of STIs,
      but further understanding of the complexity of sexual networks and networking
      methods is warranted, given increasing rates of STIs.

PMID- 29465676
TI  - Previously Diagnosed HIV-Positive Persons: The Role of Centers for Disease
      Control and Prevention-Funded HIV Testing Programs in Addressing Their Needs.
AB  - BACKGROUND: Increased HIV testing efforts have resulted in retesting previously
      diagnosed persons. This study examined Centers for Disease Control and Prevention
      (CDC)-funded HIV testing programs to evaluate how the needs of previously
      diagnosed persons are being addressed. METHODS: The following were examined by
      demographic and test setting among previously diagnosed HIV-positive persons in
      2015: CDC-funded HIV testing, previously diagnosed HIV positivity, current care
      status, and linkage to care. In addition, trends of HIV positivity and previously
      diagnosed HIV-positivity were examined from 2011 to 2015. RESULTS: In 2015, CDC
      funded 3,026,074 HIV tests, and 27,729 were HIV-positive tests. Of those, 13,528
      (48.8%) were previously diagnosed persons. Only 11.6% of previously diagnosed
      persons reported already being in HIV care; after excluding them, 62.1% of
      previously diagnosed persons were linked within 90 days. In addition, the
      percentage of previously diagnosed persons steadily increased from 2011 (25.9%)
      to 2015 (34.1%; P < 0.001). CONCLUSIONS: Almost half of all HIV-positive tests
      were among previously diagnosed persons, but only 11.6% were already in HIV care.
      Linkage is necessary among persons who already know their HIV status because they
      either were never linked or need to be reengaged into care. Barriers in linkage
      and retention among this group also need to be addressed.

PMID- 29465677
TI  - Patterns of Sexual Behavior and Sexually Transmitted Infections in Young Men Who
      Have Sex With Men.
AB  - PURPOSE: Young men who have sex with men (MSM) are at an increased risk for
      sexually transmitted infections (STIs). Recent research has documented the
      importance of understanding the multidimensional nature of sexual risk behavior;
      however, little is known about how multidimensional patterns of sexual behavior
      among MSM may be associated with STIs. METHOD: This study applies latent class
      analysis to data from a large, HIV- sample of 18- to 25-year-old MSM recruited
      from social and sexual networking Web sites (N = 5965; 76% white, 11% Latino, 5%
      black, 4% Asian, 4% other; 74% homosexual, 21% bisexual, 1% heterosexual, 3%,
      unsure/questioning 1% other) to uncover multidimensional patterns of past-year
      sexual behaviors, partner factors, and protective behavior and their associations
      with self-reported STI diagnosis. RESULTS: We selected a model with 8 classes,
      with nearly half of participants belonging to a class marked by multiple
      behaviors with more than 1 partner, and smaller numbers of individuals in classes
      with a smaller number of behaviors, romantic relationships, and sexual
      inactivity. Class membership was associated with recent STI diagnosis, with
      classes marked by no penetrative sex or receptive anal sex with consistent condom
      use having lower prevalence than those with inconsistent condom use, including
      those engaging in only insertive anal sex. CONCLUSIONS: Findings suggest
      heterogeneity of behaviors within MSM and that prevention messages may be more
      effective if they are tailored to individuals' patterns of sexual behavior, as
      well as demographic and sociocontextual factors.

PMID- 29465678
TI  - Men Who Have Sex With Men-Identification Criteria and Characteristics From the
      National Health and Nutrition Examination Survey, 1999 to 2014.
AB  - OBJECTIVES: This study aimed to provide identification criteria for men who have
      sex with men (MSM), estimate the prevalence of MSM behavior, and compare
      sociodemographics and sexually transmitted disease risk behaviors between non-MSM
      and MSM groups using data from a nationally representative, population-based
      survey. METHODS: Using data from men aged 18 to 59 years who took part in the
      National Health and Nutrition Examination Survey (NHANES), 1999 to 2014, detailed
      criteria were developed to estimate MSM behavior-at least one lifetime same-sex
      partner (MSM-ever), at least one same-sex partner in the past 12 months (MSM
      current), and at least one lifetime and zero same-sex partners in the past 12
      months (MSM-past). RESULTS: The estimated prevalence of MSM-ever was 5.5%-of
      these, 52.4% were MSM-current and 47.1% were MSM-past. Furthermore, MSM-ever are
      a nonhomogenous subpopulation, for example, 70.4% of MSM-current identified as
      homosexual and 71.2% of MSM-past identified as heterosexual (P < 0.001).
      CONCLUSIONS: The prevalence of MSM behavior identified here is similar to other
      published estimates. This is also the first article, to our knowledge, to use
      National Health and Nutrition Examination Survey data to compare MSM by 2 recall
      periods (recent vs. lifetime) of last same-sex sexual behavior.

PMID- 29465679
TI  - A Cluster Randomized Evaluation of a Health Department Data to Care Intervention
      Designed to Increase Engagement in HIV Care and Antiretroviral Use.
AB  - BACKGROUND: Many US health departments have implemented Data to Care
      interventions, which use HIV surveillance data to identify persons who are
      inadequately engaged in HIV medical care and assist them with care reengagement,
      but the effectiveness of this strategy is uncertain. METHODS: We conducted a
      stepped-wedge, cluster-randomized evaluation of a Data to Care intervention in
      King County, Washington, 2011 to 2014. Persons diagnosed as having HIV for at
      least 6 months were eligible based on 1 of 2 criteria: (1) viral load (VL)
      greater than 500 copies/mL and CD4 less than 350 cells/MUL at the last report in
      the past 12 months or (2) no CD4 or VL reported to the health department for at
      least 12 months. The intervention included medical provider contact, patient
      contact, and a structured individual interview. Health department staff assisted
      patients with reengagement using health systems navigation, brief counseling, and
      referral to support services. We clustered all eligible cases in the county by
      the last known medical provider and randomized the order of clusters for
      intervention, creating contemporaneous intervention and control periods (cases in
      later clusters contributed person-time to the control period at the same time
      that cases in earlier clusters contributed person-time to the intervention
      period). We compared the time to viral suppression (VL <200 copies/mL) for
      individuals during intervention and control periods using a Cox proportional
      hazards model. RESULTS: We identified 997 persons (intention to treat [ITT]), 18%
      of whom had moved or died. Of the remaining 822 (modified ITT), 161 (20%) had an
      undetectable VL reported before contact and 164 (20%) completed the individual
      interview. The hazard ratio (HR) for time to viral suppression did not differ
      between the intervention and control periods in ITT (HR, 1.21 [95% confidence
      interval, 0.85-1.71]) or modified ITT (HR, 1.18 [95% confidence interval, 0.83
      1.68]) analysis. CONCLUSIONS: The Data to Care intervention did not impact time
      to viral suppression.

PMID- 29465680
TI  - Genital Wart and HPV Prevalence in Males in the United States from Penile Swabs:
      Results from NHANES.
AB  - INTRODUCTION: Human papillomavirus (HPV) is a common sexually transmitted
      infection in the US that can lead to both malignant (high risk) and benign (low
      risk) findings. These low risk findings include both genital condyloma, anal
      warts, and adult or juvenile papillomatosis, which are directly attributable to
      subtypes HPV 6 and HPV 11. We aim to estimate the prevalence of genital wart
      infections in males in the US population using a nationwide sample. METHODS: The
      NHANES database was queried for all men 18-59 years old during the years 2013
      2014. During these years, the survey included penile swabs that were tested for
      HPV infection from 37 subtypes using PCR. Information was also obtained regarding
      patient reported history of having a genital wart infection previously. RESULTS:
      A total of 1,757 men had information regarding HPV DNA. Fifty-three men tested
      positive for HPV 6 or HPV 11 DNA. This corresponds to an estimated prevalence of
      2.9% (95% CI 2.2-3.8) of men aged 18-59 years. In addition, 2.2% (95% CI 1.5-3.3)
      of men reported a history of genital wart infection. There was no significant
      association with genital HPV DNA detection with age. Increasing number of sexual
      partners was associated with higher rates of both genital warts and HPV 6 and HPV
      11 DNA. CONCLUSIONS: The estimated prevalence of genital HPV DNA in the US male
      population is 2.9%. This burden of disease could potentially be lowered with
      increased usage of quadrivalent and nonavalent vaccinations.

PMID- 29465681
TI  - A Population-Based Study to Compare Treatment Outcomes Among Women With
      Urogenital Chlamydial Infection in Washington State, 1992 to 2015.
AB  - BACKGROUND: United States guidelines recommend azithromycin or doxycycline for
      chlamydia (Chlamydia trachomatis [CT]) treatment. These therapies are similarly
      efficacious for urogenital infections when outcomes are measured 7 to 42 days
      after treatment, although doxycycline may be superior for rectal infections. Some
      investigators have suggested that persistent rectal infections may lead to
      autoinfection of the urogenital tract, potentially resulting in higher rates of
      recurrent infection in azithromycin-treated women. METHODS: We used Washington
      State surveillance data to identify women 14 years or older with urogenital CT
      (1992-2015) treated with azithromycin or doxycycline. We defined
      persistent/recurrent CT as a repeat positive CT test result 14 to 180 days after
      treatment of the initial infection. We used log binomial regression to estimate
      the adjusted relative risk (aRR) of persistent/recurrent infection associated
      with treatment with azithromycin versus doxycycline. RESULTS: From 1992 to 2015,
      there were 268,596 reported cases of urogenital CT, including 168,301 (63%) who
      received azithromycin and 66,432 (25%) who received doxycycline. The risk of
      persistent/recurrent urogenital CT was 6.7% and 4.7% in azithromycin- and
      doxycycline-treated cases, respectively (P < 0.001). Adjusting for age,
      race/ethnicity, year, pregnancy status, jurisdiction reporting, reason for
      examination, and gonorrhea coinfection, azithromycin-treated women were
      significantly more likely to have persistent/recurrent urogenital CT than
      doxycycline-treated women (aRR, 1.24; 95% confidence interval [CI], 1.19-1.30).
      Adjusting the retesting window to 21 to 180 days (aRR, 1.24; 95% CI, 1.19-1.30)
      and 28 to 180 days (aRR, 1.25; 95% CI, 1.19-1.30) did not alter our primary
      findings. CONCLUSIONS: Persistent/recurrent urogenital CT may be more common
      among women treated with azithromycin than with doxycycline. The reason for this
      difference is uncertain and is an important area of future investigation.

PMID- 29465682
TI  - Variability in Condom Use Trends by Sexual Risk Behaviors: Findings from the 2003
      2015 National Youth Risk Behavior Surveys.
AB  - OBJECTIVE: This study aimed to examine variability in condom use trends by sexual
      risk behavior among US high school students. METHODS: Data were from the 2003
      2015 national Youth Risk Behavior Surveys conducted biennially among a nationally
      representative sample of students in grades 9 to 12. We used logistic regression
      to examine variability in trends of condom use during last sexual intercourse
      among female and male students by 4 sexual risk behaviors: drank alcohol or used
      drugs before last sexual intercourse, first sexual intercourse before age 13
      years, 4 or more sex partners during their life, and 2 or more sex partners
      during the past 3 months. RESULTS: Between 2003 and 2015, significant declines in
      self-reported condom use were observed among black female (63.6% in 2003 to 46.7%
      in 2015) and white male students (69.0% in 2003 to 58.1% in 2015). Among female
      students, declines in self-reported condom use were significant only among those
      who drank or use drugs before last sexual intercourse, had 4 or more sex partners
      during their life, or had 2 or more sex partners during the past 3 months. There
      was a significant interaction between trends in condom use and first sexual
      intercourse before age 13 years, suggesting more pronounced declines among female
      students who initiated first sexual intercourse before age 13 years compared with
      their female peers. Trends did not vary by sexual risk behavior for male
      students. CONCLUSIONS: Results suggest that declines in self-reported condom use
      have occurred among female students at greater risk for acquiring a sexually
      transmitted disease.

PMID- 29465683
TI  - Chemsex Among Men Who Have Sex With Men: a Sexualized Drug Use Survey Among
      Clients of the Sexually Transmitted Infection Outpatient Clinic and Users of a
      Gay Dating App in Amsterdam, the Netherlands.
AB  - OBJECTIVES: Chemsex (i.e., drug use during sex) is practiced by some men who have
      sex with men (MSM) and is associated with high-risk behavior. In a cross
      sectional study at the sexually transmitted infection (STI) clinic of Amsterdam,
      we explored chemsex practices, risk behavior, and STI prevalence. METHOD: A
      survey on chemsex (gamma-hydroxybutyrate, crystal methamphetamine, and/or
      mephedrone) was offered to clinic clients during routine STI screening and to
      Amsterdam users of a gay online dating app. Associations were assed using chi
      test and multivariable regression. RESULTS: Chemsex in the past 6 months was
      practiced by 866 (17.6%) of 4925 MSM clients and by 159 (1.5%) of 10857 non-MSM
      clients. Among gay dating app users, the proportion that reported chemsex
      engagement was higher than among MSM visiting the STI clinic (29.3% [537/1832]
      vs. 17.6%; P < 0.001). Chemsex was a significant risk factor for bacterial STI in
      HIV-negative MSM visiting the STI clinic (adjusted odd ratio, 1.5; 95% confidence
      interval, 1.2-1.8), but not in HIV-positive MSM. A majority practiced chemsex
      once a month or less, and 87.0% reported sex without drug use in the past month.
      CONCLUSIONS: In Amsterdam, chemsex is frequently practiced and significantly
      associated with bacterial STI in HIV-negative MSM but not in HIV-positive MSM.
      Future prevention strategies to reduce STI incidence should especially target HIV
      negative MSM engaging in chemsex.

PMID- 29465684
TI  - Screening for Trichomonas vaginalis in a Large High-Risk Population: Prevalence
      Among Men and Women Determined by Nucleic Acid Amplification Testing.
AB  - Men and women attending family planning and sexually transmitted disease clinics
      for sexually transmitted infection screening in 2012 to 2013 were tested for
      Trichomonas vaginalis (TV) using a sensitive nucleic acid amplification test. T.
      vaginalis prevalence in urogenital samples was 11.3% in 77,740 women and 6.1% in
      12,604 men, and increased with age in both sexes.

PMID- 29465685
TI  - Ciprofloxacin May be Efficacious in Treating Wild-Type Gyrase A Genotype
      Neisseria gonorrhoeae Infections.

PMID- 29465686
TI  - Prevalence and Detection of Trichomonas vaginalis in HIV-Infected Pregnant Women.
AB  - BACKGROUND: Trichomonas vaginalis is a sexually transmitted infection associated
      with increased transmission of HIV and significant adverse birth outcomes;
      culture and polymerase chain reaction (PCR) are commonly used in diagnosis.
      METHODS: Consenting HIV-infected pregnant women were recruited from clinics in
      South Africa and screened for T. vaginalis using PCR. Polymerase chain reaction
      positive women provided an additional sample for culture. We compared T.
      vaginalis detection between PCR and culture, and investigated how PCR cycle
      threshold (Ct) values differ among culture results. RESULTS: A total of 359 women
      were enrolled and 76 (20%) tested T. vaginalis PCR positive. Cultures were
      obtained from 61 of the PCR-positive women, and 38 (62%) were culture positive.
      The median baseline Ct of the PCR-positive/culture-positive group was 22.6 versus
      38.0 among those who were PCR positive/culture negative (P < 0.001). Culture
      positive cases had lower Ct values (higher DNA load); a Ct value less than 30
      predicted positivity with a sensitivity of 97% and a specificity of 96%.
      CONCLUSIONS: Culture was positive in roughly half of PCR-positive cases. The
      culture-negative cases had significantly higher Ct values, indicating a lower
      concentration of T. vaginalis DNA. A Ct value of 30 provides a reliable threshold
      for predicting culture positivity. The clinical significance of culture-negative
      infections detected by PCR is still unclear.

PMID- 29465687
TI  - Molecular Characterization of Markers Associated With Antimicrobial Resistance in
      Neisseria gonorrhoeae Identified From Residual Clinical Samples.
AB  - BACKGROUND: The emergence and spread of antimicrobial-resistant (AMR) Neisseria
      gonorrhoeae (NG) is a major public health concern. In the era of nucleic acid
      amplifications tests, rapid and accurate molecular approaches are needed to help
      increase surveillance, guide antimicrobial stewardship, and prevent outbreaks.
      METHODS: Residual urethral swabs, collected prospectively in the Baltimore City
      Health Department during a 6-month period, were analyzed by real-time polymerase
      chain reaction assays for NG DNA and AMR determinants to fluoroquinolones,
      penicillin, and extended-spectrum cephalosporins. RESULTS: N. gonorrhoeae DNA was
      detected in 34.8% (73/210) of samples, including 67.3% (68/101) of the swabs that
      had been previously identified as NG positive by culture. Markers associated with
      decreased susceptibility to fluoroquinolones were detected in 22.4% of the
      polymerase chain reaction NG-positive samples. The rate of penicillinase
      producing NG was very low (1.6%), and no markers associated with decreased
      susceptibility to extended-spectrum cephalosporins were detected in this cohort
      of men using the AMR assays herein described. CONCLUSIONS: Detection of molecular
      markers associated with AMR in NG can be performed directly from residual
      clinical samples, although the recovery rate of adequate DNA for molecular
      testing from these samples can be suboptimal. A high number of samples with
      mutations associated with decreased susceptibility to fluoroquinolones were
      identified.

PMID- 29465688
TI  - Prevalence of Rectal Chlamydial and Gonococcal Infections: A Systematic Review.
AB  - We undertook a systematic review to examine rectal Chlamydia trachomatis (Ct) and
      Neisseria gonorrhoeae (Ng) infections in women and men who have sex with men
      (MSM). English-language publications measuring rectal Ct or Ng prevalence using
      nucleic acid amplification tests were eligible. Searching multiple electronic
      databases, we identified 115 eligible reports published between January 2000 and
      November 2016. Overall, the prevalence of rectal Ct (9%) was higher than that of
      rectal Ng (4.7%). Rectal Ct prevalence was similar in MSM (9%) and women (9.2%),
      whereas rectal Ng prevalence was higher in MSM (6.1%) than in women (1.7%).
      Generally, rectal Ct prevalence was similar in sexually transmitted disease
      clinics (9.1%) and nonsexual health clinics (8.6%), whereas rectal Ng prevalence
      was somewhat lower in sexually transmitted disease clinics (4.5%) than in
      nonsexual health clinics (6%). These infections seem to be relatively common
      across a range of populations and clinical settings, highlighting the need for
      additional research on these preventable, treatable conditions.

PMID- 29465689
TI  - Expedited Partner Therapy: Pharmacist Refusal of Legal Prescriptions.
AB  - BACKGROUND: Expedited partner therapy (EPT) is an effective strategy for partner
      management of sexually transmitted infections. Some states, including Wisconsin,
      allow EPT prescriptions to be filled without a patient name. This study
      determined the refusal rates of nameless EPT prescriptions in Milwaukee
      pharmacies. METHODS: In this cross-sectional study, 3 trained research assistants
      of different age, sex, and race posed as "patients" and visited 50 pharmacy
      locations from one pharmacy chain in Milwaukee County, WI, to fill nameless EPT
      prescriptions. A chi test was used to compare demographics of patients,
      pharmacists, and pharmacies. Multiple logistic regression was used to identify
      factors associated with prescription refusal. RESULTS: Twenty-nine (58%) of 50
      nameless EPT prescriptions were refused. Univariate analysis showed that
      prescriptions were more likely to be refused if the pharmacy was in the suburbs
      (77%) compared with Milwaukee city (43%; P = 0.01), if the pharmacist was older
      than the patient (82%) compared with being younger (46%) or within the same age
      group (33%; P = 0.01 for both), and if the patient was white (78%) compared with
      nonwhite (47%; P = 0.03). Multivariable regression revealed significantly higher
      refusals for pharmacies located in the suburbs compared with the city (odds
      ratio, 5.3; 95% confidence interval, 1.4-20.3; P = 0.03) and in patients who were
      white compared with nonwhite (odds ratio: 4.8; 95% confidence interval, 1.2-19.8;
      P = 0.01). CONCLUSIONS: More than half of nameless EPT prescriptions were refused
      in Milwaukee county pharmacies, more frequently at suburban pharmacies and for
      white patients. Increased pharmacist education regarding EPT is essential to help
      combat the sexually transmitted infection crisis.

PMID- 29465691
TI  - Is There a Continuum of Risk for Sexually Transmitted Infections Among African
      American Women?
AB  - This study compared sexual risk behaviors and sexually transmitted infection
      prevalence among African American women who have sex with women, women who have
      sex with men with a single male partner, women who have sex with men with 4 or
      more male partners, and women who have sex with women and men at a sexually
      transmitted disease clinic. The results suggest that, despite differences in
      prevalence, there was not a clear continuum of sexually transmitted infection
      risk among African American women in the study; all women were at risk.

PMID- 29465690
TI  - Conceptualizing Geosexual Archetypes: Mapping the Sexual Travels and Egocentric
      Sexual Networks of Gay and Bisexual Men in Toronto, Canada.
AB  - BACKGROUND: There are complex, synergistic, and persistent sexually transmitted
      infection (STI) epidemics affecting gay, bisexual and other men who have sex with
      men (gbMSM) in every major urban centre across North America. We explored the
      spatial architecture of egocentric sexual networks for gbMSM in Toronto, Canada.
      METHODS: Our integrative mixed methods study included in-depth interviews with 31
      gbMSM between May and July 2016. During interviews, participants mapped their
      egocentric sexual network for the preceding 3 months geographically. At the end,
      a self-administered survey was used to collect sociodemographic characteristics,
      online technology use, and STI testing and history. RESULTS: We identified 6
      geosexual archetypes: hosters, house-callers, privates, rovers, travellers, and
      geoflexibles. Hosters always, or almost always (>=80%), hosted sex at their home.
      House-callers always, or almost always (>=80%), had sex at their partner's home.
      Rovers always or almost always (>=80%) had sex at public venues (eg, bath houses,
      sex clubs) and other public spaces (eg, parks, cruising sites). Privates had sex
      in private-their own home or their partner's (part hoster, part house-caller).
      Travellers had sex away from their home, either at a partner's home or some other
      venue or public space (part house-caller, part rover). Geoflexibles had sex in a
      variety of locations-their home, their partner's home, or public venues. All
      hosters and rovers, and to a lesser extent, geoflexibles, reported a history of
      syphilis and human immunodeficiency virus. CONCLUSIONS: Prioritizing
      interventions to hosters, rovers, and geoflexibles may have an important impact
      on reducing STI transmission.

PMID- 29465692
TI  - Molecular Typing and Macrolide Resistance of Syphilis Cases in Manitoba, Canada,
      From 2012 to 2016.
AB  - BACKGROUND: The province of Manitoba, Canada, with a population of approximately
      1.3 million, has been experiencing increased incidence of syphilis cases since
      2015. In this study, we examined the detection of Treponema pallidum DNA in 354
      clinical samples from 2012 to 2016, and determined molecular types and mutations
      conferring resistance to azithromycin in the polymerase chain reaction (PCR)
      positive samples. METHODS: T. pallidum DNA detection was done by PCR
      amplification of tpp47, bmp, and polA genes. Syphilis serology results were
      reviewed for the PCR-positive cases. Molecular typing of syphilis strains was
      done by analysis of the T, pallidum arp, tpr, and tp0548 gene targets as well as
      partial sequencing of the 23S rRNA gene for azithromycin resistance. RESULTS: Of
      the 354 samples tested, 74 individual cases were PCR positive. A result from the
      treponemal antibody chemiluminescent microparticle immunoassay test was positive
      in 72 of these cases and that from the Venereal Disease Research Laboratory
      testing was positive in 66. Mutations conferring resistance to azithromycin were
      found in all 74 PCR-positive samples. Molecular typing was completed on 57 PCR
      positive samples, and 12 molecular types were identified with 14d/g found in
      63.2%. Increased strain diversity was observed with 8 molecular types detected in
      2016, whereas only 2 to 3 types were found in 2012 to 2014. A patient with 2
      episodes of infection 9 months apart caused by different molecular strain types
      was also identified. CONCLUSIONS: The finding of an increase in genetic diversity
      in the strains in this study and an increase in macrolide resistance compared
      with previous Canadian reports highlighted the need for continued surveillance
      including strain characterization.

PMID- 29465693
TI  - Scaling Up Human Immunodeficiency Virus Screening and Antiretroviral Therapy
      Among Men Who Have Sex With Men to Achieve the 90-90-90 Targets in China.
AB  - INTRODUCTION: The Joint United Nations Programme on human immunodeficiency virus
      (HIV)/acquired immune deficiency syndrome has proposed the 90-90-90 targets by
      2020. Human immunodeficiency virus epidemic is spreading rapidly among men who
      have sex with men (MSM) in China. This study investigates how the scale-up of HIV
      testing and treatment in achieving the targets and its cost-effectiveness.
      METHODS: We constructed a compartmental model to forecast the HIV epidemic in
      Chinese MSM based on various "test-and-treat" scale-up scenarios. We assessed
      their cost effectiveness based on the cost for each HIV infection, death, and
      disability-adjusted life years (DALYs) prevented by the scale-up. RESULTS: If the
      current epidemic continued, HIV prevalence among Chinese MSM would increase from
      9.2% in 2016 to 12.6% (9.2-15.6%) in 2020 and 16.2% (11.3-20.0%) in 2025. By
      2020, 49.2% of infected MSM would be diagnosed and 40.1% of whom on treatment,
      falling short of the 90-90-90 targets, so would be even by 2025. To achieve these
      targets by 2020, additional 850,000 HIV screening tests and 112,500 person-years
      of antiretroviral treatment (ART) annually are necessary. This spending is US
      $478 million during 2016 to 2020, which almost tripled the status quo. However,
      by delaying to 2025, an investment of US $1210 million over 2016 to 2025
      corresponding to 52% increase to the status quo, will enable extra 340,000 HIV
      screening tests and 60,000 person-year on ART annually. In both scenarios, the
      incremental cost-effectiveness ratio was US $733 to 960 for each DALY prevented,
      indicating highly cost-effective scenarios. CONCLUSIONS: Achieving the 90-90-90
      targets by 2020 requires steep increase in investment, but delaying the targets
      to 2025 is practical and cost-effective.

PMID- 29465694
TI  - Hepatitis B Vaccination and Infection Prevalence Among Men Who Have Sex With Men
      Who Travel Internationally.
AB  - Among men who have sex with men traveling internationally, self-reported
      hepatitis B virus (HBV) vaccination prevalence was 77% and less prevalent among
      older men and those with HBV infection. The HBV infection prevalence was 25% and
      was associated with older age and HIV infection. Testing for chronic infection,
      universal vaccination, and treatment for populations with multiple risks is
      needed.

PMID- 29465695
TI  - Extragenital Chlamydia and Gonorrhea in Young Black Men Who Have Sex With Men:
      Missed Treatment Opportunities for Human Immunodeficiency Virus-Infected Men Who
      Have Sex With Men?
AB  - OBJECTIVES: This study of young black men who have sex with men (YBMSM) assessed
      the prevalence of extragenital chlamydia and gonorrhea among those testing
      negative for urethral infections, and compared prevalence of both by human
      immunodeficiency virus (HIV) status. METHODS: A convenience sample of 609 YBMSM
      was recruited for a cross-sectional study from 2 sexual health clinics located in
      Jackson, MS. To detect Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG),
      nucleic acid amplification testing was performed on urine, rectal swabs, and oral
      swabs. OraSure was used to detect HIV. RESULTS: Seventy-three percent of all
      chlamydia infections and 77% of gonorrhea infections were found from anal and
      oral swabs in the absence of urethral positivity. Compared with HIV-uninfected
      men, HIV-infected men were significantly more likely to have pharyngeal chlamydia
      (P = 0.03), multiple CT infections (P = 0.02), rectal NG (P < 0.001), multiple NG
      infections (P = 0.04), both CT/NG rectal infections (P = 0.001). CONCLUSIONS: As
      much as three quarters of all chlamydia and gonorrhea infections may be missed
      when only urine-based nucleic acid amplification testing is used to screen YBMSM
      for bacterial sexually transmitted infections. These missed opportunities for
      diagnosis may be particularly likely among HIV-infected YBMSM.

PMID- 29465696
TI  - Integrated Hepatitis C Testing and Linkage to Care at a Local Health Department
      Sexually Transmitted Disease Clinic: Determining Essential Resources and
      Evaluating Outcomes.
AB  - Guidance about integration of comprehensive hepatitis C virus (HCV)-related
      services in sexually transmitted disease (STD) clinics is limited. We evaluated a
      federally funded HCV testing and linkage-to-care program at an STD clinic in
      Durham County, North Carolina. During December 10, 2012, to March 31, 2015, the
      program tested 733 patients for HCV who reported 1 or more HCV risk factor; 81
      (11%) were HCV-infected (ie, HCV antibody-positive and HCV ribonucleic acid
      positive). Fifty-one infected patients (63%) were linked to care. We concluded
      that essential program resources include reflex HCV ribonucleic acid testing; a
      dedicated bridge counselor to provide test results, health education, and linkage
      to-care assistance; and referral relationships for local HCV management and
      treatment.

PMID- 29465698
TI  - Enhanced Molecular Typing of Treponema pallidum subspecies pallidum Strains From
      4 Italian Hospitals Shows Geographical Differences in Strain Type Heterogeneity,
      Widespread Resistance to Macrolides, and Lack of Mutations Associated With
      Doxycycline Resistance.
AB  - BACKGROUND: Although syphilis rates have been relatively high in Italy for more
      than 15 years, no data on the molecular types of Treponema pallidum subspecies
      pallidum circulating in this country are yet available. Likewise, no data on how
      widespread is resistance to macrolide or tetracycline antibiotics in these
      strains exist. Such data would, however, promote comprehensive studies on the
      molecular epidemiology of syphilis infections in Italy and inform future
      interventions aiming at syphilis control in this and other European countries.
      GOALS AND STUDY DESIGN: Swabs from oral, genital, cutaneous, or anal lesions were
      obtained from 60 syphilis patients attending dermatology clinics in Milan, Turin,
      Genoa, and Bologna. Molecular typing of T. pallidum DNA was performed to provide
      a snapshot of the genetic diversity of strains circulating in Northern Italy.
      Samples were also screened for mutations conferring resistance to macrolides and
      tetracyclines. RESULTS: T. pallidum DNA was detected in 88.3% (53/60) of the
      specimens analyzed. Complete and partial T. pallidum typing data were obtained
      for 77.3% (41/53) and 15.0% (8/53) of samples, respectively, whereas 4 samples
      could not be typed despite T. pallidum DNA being detected. The highest strain
      type heterogeneity was seen in samples from Bologna and Milan, followed by Genoa.
      Minimal diversity was detected in samples from Turin, despite the highest number
      of typeable samples collected there. Resistance to macrolides was detected in
      94.3% (50/53) of the strains, but no known mutations associated with tetracycline
      resistance were found. CONCLUSIONS: Genetic diversity among T. pallidum strains
      circulating in Northern Italy varies significantly among geographical areas
      regardless of physical distance. Resistance to macrolides is widespread.

PMID- 29465699
TI  - Early Evidence of the Effectiveness of the Human Papillomavirus Vaccination
      Program Against Anogenital Warts in Manitoba, Canada: A Registry Cohort Study.
AB  - BACKGROUND: We assessed the effectiveness of the quadrivalent human
      papillomavirus vaccine (qHPV) vaccination program in Manitoba, Canada, in
      reducing incident anogenital warts (AGWs) and to what extent effectiveness
      depends on age at vaccination and number of doses. METHODS: Female participants 9
      years or older who received the qHPV in Manitoba between September 2006 and March
      2013 (n = 31,464) through the publicly funded school-based program and a high
      risk catch-up program were included. They were matched on age and area of
      residence to unvaccinated female participants. Information on incident AGWs was
      obtained from provincial administrative databases using validated algorithms.
      Using stratified Cox regression models, we estimate hazard ratios (HRs) for the
      association between qHPV and AGWs. RESULTS: For female participants vaccinated at
      age 18 years or younger, receipt of qHPV was associated with a 40% reduction in
      AGW risk (HR, 0.6; 95% confidence interval [CI], 0.4-0.8). Further adjustment for
      socioeconomic and medical history did not alter this estimate. For women
      vaccinated at age 19 years or older, we saw an increase in AGW incidence,
      especially among those who were sexually active (HR, 2.8; 95% CI, 2.1-3.7). Among
      female participants vaccinated at age 18 years or younger, risk of AGWs was
      lowest among those who received 3 doses, corresponding to a vaccine effectiveness
      of 56% (95% CI, 30%-70%). For women vaccinated at older age, risk of AGWs
      remained increased regardless of the number of doses. CONCLUSIONS: Women
      vaccinated at an older (>=19 years) age may be less protected against AGWs,
      particularly if sexually active before vaccine administration. Further efforts
      should be targeted at increasing vaccine uptake among preadolescents before the
      initiation of sexual activity.

PMID- 29465700
TI  - SENDER AND RECEIVER ACCEPTABILTY AND USABILTY OF AN ONLINE PARTNER NOTIFICATION
      TOOL FOR STI IN THE NETHERLANDS.
AB  - Users (index patients with a verified STI and notified partners) rated the health
      care provider initiated Internet-based partner notification application
      Suggestatest.nl acceptable and usable. Both groups were less positive about
      Suggestatest.nl to notify /get notified of HIV than of other STI. An anonymous
      notification was perceived less acceptable.

PMID- 29465701
TI  - Optimizing Screening for Sexually Transmitted Infections in Men Using Self
      Collected Swabs: A Systematic Review.
AB  - BACKGROUND: Sexually transmitted infection (STI) rates are increasing in the
      United States while funding for prevention and treatment programs has declined.
      Sample self-collection for STI testing in men may provide an acceptable, easy,
      rapid, and potentially cost-effective method for increasing diagnosis and
      treatment of STIs. METHODS: We conducted a systematic review of articles
      assessing self-collection of anal, oral, or genital swab samples among adult men
      for detection of STIs and/or human papillomavirus-related dysplasia. We searched
      for English-language articles in which men 18 years or older were recruited to
      participate. RESULTS: Our literature search resulted in 1053 citations, with 20
      meeting inclusion criteria. Self-collection methods were highly sensitive and
      comparable with clinician collection for detection of multiple STI pathogens.
      However, self-collected samples were less likely to be of adequate quality for
      anorectal cytology and less sensitive for detection of anal intraepithelial
      neoplasia than clinician-collected samples. Self-collection was highly
      acceptable. Overall, studies were small and heterogeneous and used designs
      providing lower levels of evidence. CONCLUSIONS: Self-collection methods are a
      viable option for collecting samples for STI testing in adult men based on their
      high feasibility, acceptability, and validity. Implementation of self-collection
      procedures in STI testing venues should be performed to expand opportunities for
      STI detection and treatment.

PMID- 29465702
TI  - Narrative Review: Assessment of Neisseria gonorrhoeae Infections Among Men Who
      Have Sex With Men in National and Sentinel Surveillance Systems in the United
      States.
AB  - To assess trends in Neisseria gonorrhoeae among gay, bisexual, and other men who
      have sex with men (MSM), we reviewed existing and published gonorrhea
      surveillance data in the United States. Data identified in this review include
      the following: national gonorrhea case report data and data from 3 other
      surveillance programs, the Gonococcal Isolate Surveillance Project (GISP), the
      STD Surveillance Network (SSuN), and National HIV Behavioral Surveillance.Rates
      of reported cases of gonorrhea among men increased 54.8% in 2006 to 2015 compared
      with a 2.6% increase among women. Since 2012, the rate of reported gonorrhea
      cases among men surpassed the rate among women; the male-to-female case rate
      ratio increased from 0.97 in 2012 to 1.31 in 2015. The proportion of gonococcal
      urethral isolates collected in the Gonococcal Isolate Surveillance Project that
      were collected from MSM increased from 21.5% to 38.1% in 2006 to 2015. In 2009 to
      2015, the percent of MSM who tested positive for rectal and oropharyngeal
      gonorrhea in sexually transmitted disease (STD) clinics increased by 73.4% and
      12.6%, respectively. Estimated rates of gonorrhea among MSM increased by 151% in
      2010 to 2015 in jurisdictions participating in the STD Surveillance Network. Data
      from the National HIV Behavioral Surveillance demonstrate that testing for
      gonorrhea among MSM increased by 23.1% between 2011 and 2014.Together,
      surveillance data suggest a disproportionate burden of gonorrhea among MSM in the
      United States and suggest increases in both screening and disease in recent
      years. Because each data source has inherent limitations and biases, examining
      these data from different systems together strengthens this conclusion.

PMID- 29465703
TI  - An Exploration of Factors Impacting Preexposure Prophylaxis Eligibility and
      Access Among Syringe Exchange Users.
AB  - BACKGROUND: In 2015, approximately 50,000 new HIV infections occurred in the
      United States, 2,400 of which were attributable to injection drug use.
      Preexposure prophylaxis (PrEP) has the potential to curb HIV acquisition;
      however, uptake remains low among persons who inject drugs (PWID). The purpose of
      the study is to describe PrEP eligibility, willingness to use PrEP, and ability
      to access PrEP among PWID recruited from a pilot program that paired screening
      and treatment of sexually transmitted infections with mobile syringe exchange
      program (SEP) services. METHODS: Between 2015 and 2016, 138 PWID 18 years or
      older were recruited from a mobile SEP in Camden, New Jersey. Participants
      completed a survey assessing sociodemographics and HIV risk and underwent
      chlamydia and gonorrhea screening. Centers for Disease Control clinical
      guidelines were used to calculate PrEP eligibility. Differences by sex were
      examined using inferential statistics. RESULTS: Most women (95.4%) and men
      (84.5%) were considered PrEP eligible (P < 0.04). More women than men were
      willing to take PrEP (88.9% vs. 71.0%; P < 0.02). Participants reported
      substantial barriers to PrEP including feeling embarrassed (45.0%) or anxious
      (51.6%) about taking PrEP, nondisclosure to partners (51.4%), limited engagement
      with health care providers where PrEP might be provided (43.8%), and lacking
      health insurance (32.9%). CONCLUSIONS: Despite reporting behavior that warrants
      the use of PrEP to prevent HIV and finding the concept acceptable, PWID face
      multiple barriers to PrEP access. Without tailored interventions to promote PrEP,
      uptake will likely remain suboptimal. Packaging PrEP with SEP services could
      provide a viable option for reaching eligible and interested PWID.

PMID- 29465704
TI  - Gonococcal and Chlamydial Cases of Pelvic Inflammatory Disease at 2 Canadian
      Sexually Transmitted Infection Clinics, 2004 to 2014: A Retrospective Cross
      sectional Review.
AB  - One hundred thirteen patients with gonococcal and chlamydial pelvic inflammatory
      disease were reviewed at 2 Canadian sexually transmitted infection clinics. Most
      patients (81%) with pelvic inflammatory disease were diagnosed as having
      chlamydia alone. Three treatment failures were seen in patients treated with
      ofloxacin.

PMID- 29465705
TI  - Non-Vaccine-Type Human Papillomavirus Prevalence After Vaccine Introduction: No
      Evidence for Type Replacement but Evidence for Cross-Protection.
AB  - BACKGROUND: We examined non-vaccine-type human papillomavirus (HPV) prevalence in
      a community before and during the first 8 years after vaccine introduction, to
      assess for (1) type replacement with any non-vaccine-type HPV and (2) cross
      protection with non-vaccine types genetically related to vaccine-type HPV.
      METHODS: Sexually experienced 13- to- 26-year-old women were recruited for 3
      cross-sectional studies from 2006 to 2014 (N = 1180). Outcome variables were as
      follows: (1) prevalence of at least 1 of 32 anogenital non-vaccine-type HPVs and
      (2) prevalence of at least 1 HPV type genetically related to HPV-16 and HPV-18.
      We determined changes in proportions of non-vaccine-type HPV prevalence across
      the study waves using logistic regression with propensity score inverse
      probability weighting. RESULTS: Vaccine initiation rates increased from 0% to
      71.3%. Logistic regression demonstrated that from 2006 to 2014, there was no
      increase in non-vaccine-type HPV among vaccinated women (adjusted odds ratio
      [AOR], 1.02; 95% confidence interval [CI], 0.73-1.42), but an increase among
      unvaccinated women (AOR, 1.88; 95% CI, 1.16-3.04). Conversely, there was a
      decrease in types genetically related to HPV-16 among vaccinated (AOR, 0.57; 95%
      CI, 0.38-0.88) but not unvaccinated women (AOR, 1.33; 95% CI, 0.81-2.17).
      CONCLUSIONS: We did not find evidence of type replacement, but did find evidence
      of cross-protection against types genetically related to HPV-16. These findings
      have implications for cost-effectiveness analyses, which may impact vaccine
      related policies, and provide information to assess the differential risk for
      cervical cancer in unvaccinated and vaccinated women, which may influence
      clinical screening recommendations. The findings also have implications for
      public health programs, such as health messaging for adolescents, parents, and
      clinicians about HPV vaccination.

PMID- 29465706
TI  - Creating Innovative STI Testing Options for University Students: the Impact of an
      STI Self-testing Program.
AB  - BACKGROUND: National-level data suggest that STI testing rates among young adults
      are low. The purpose of this study was to evaluate the acceptability of an STI
      self-testing program at a university health center. Few evaluations have been
      conducted on the acceptability of collegiate self-testing programs and their
      effect on testing uptake. METHODS: To assess acceptability and uptake of self
      testing (urine and SCVS), we conducted a brief self-administered survey of
      students accessing a large US-based university health center from January -
      December 2015. RESULTS: In 2015, University Health Services experienced a 28.5%
      increase in CT/GC testing for males and 13.7% increase in testing for females
      compared to 2013 (baseline). In 2015, 12.4% of males and 4.8% of females tested
      positive for CT/GC via clinician testing, while 12.9% of males and 12.4% of
      females tested positive via self-testing. Females were more likely to test
      positive for CT/GC when selected to test via self-test versus a clinician test,
      X(1, N = 3068) = 36.54, p<.01; no significant difference in testing type was
      observed for males. Overall, 22.5% of students who opted for the self-test option
      completed the acceptability survey; 63% reported their main reason for testing
      was unprotected sex. In the past year, 42% reported 4>= partners. The majority
      were very satisfied and likely to use the service again (82%). CONCLUSIONS: Self
      testing may be an efficient and effective way to provide STI testing for
      students, and increase testing uptake. Self-reports of multiple partners,
      unprotected sex, and detected infections suggest that at-risk students are using
      the service.

PMID- 29465707
TI  - Improving Insurance and Health Care Systems to Ensure Better Access to Sexually
      Transmitted Disease Testing and Prevention.

PMID- 29465709
TI  - An Illustration of the Potential Health and Economic Benefits of Combating
      Antibiotic-Resistant Gonorrhea.
AB  - Preventing the emergence of ceftriaxone-resistant Neisseria gonorrhoeae can
      potentially avert hundreds of millions of dollars in direct medical costs of
      gonorrhea and gonorrhea-attributable HIV infections. In the illustrative scenario
      we examined, emerging ceftriaxone resistance could lead to 1.2 million additional
      N. gonorrhoeae infections within 10 years, costing $378.2 million.

PMID- 29465708
TI  - Integration of Contact Tracing and Phylogenetics in an Investigation of Acute HIV
      Infection.
AB  - BACKGROUND: The integration of traditional contact tracing with HIV sequence
      analyses offers opportunities to mitigate some of the barriers to effective
      network construction. We used combined analyses during an outbreak investigation
      of spatiotemporally clustered acute HIV infections to evaluate if the observed
      clustering was the product of a single outbreak. METHODS: We investigated acute
      and recent HIV index cases reported in North Carolina from 2013 to 2014 and their
      reported contacts. Contact tracing networks were constructed with surveillance
      data and compared with phylogenetic transmission clusters involving an index case
      using available HIV-1 pol sequences including 1672 references. Clusters were
      defined as clades of 2 or more sequences with a less than 1.5% genetic distance
      and a bootstrap of at least 98% on maximum-likelihood phylogenies. RESULTS: In
      total, 68 index cases and 210 contacts (71 HIV infected) were reported. The
      contact tracing network involved 58 components with low overall density (1.2%
      statewide); 33% of first-degree contacts could not be located. Among 38 (56%) of
      68 index cases and 34 (48%) of 71 contacts with sequences, 13 phylogenetic
      clusters were identified (size 2-4 members). Four clusters connected network
      components that were not linked in contact tracing. The largest component (n = 28
      cases) included 2 distinct phylogenetic clusters and spanned 2 regions.
      CONCLUSIONS: We identified the concurrent expansion of multiple small
      transmission clusters rather than a single outbreak in a largely disconnected
      contact tracing network. Integration of phylogenetic analyses provided timely
      information on transmission networks during the investigation. Our findings
      highlight the potential of combined methods to better identify high-risk networks
      for intervention.

PMID- 29465710
TI  - Blood pressure variability increases with advancing chronic kidney disease stage:
      a cross-sectional analysis of 16 546 hypertensive patients.
AB  - OBJECTIVE: Increased BP-variability predicts cardiovascular morbidity and
      mortality in hypertensives. This study aimed to examine short-term BP-variability
      according to renal function stage. METHODS: We included 16 546 patients [10 270
      (62.1%) without/6276 (38.9%) with CKD Stage 1-5] from the Spanish Ambulatory
      Blood-Pressure Monitoring (ABPM) Registry. Stages of CKD were defined according
      to K/DIGO criteria, based on estimated glomerular filtration rate calculated with
      the CKD-EPI equation and albumin-to-creatine ratio. BP-variability was assessed
      with standard deviation (SD), weighted SD (wSD), coefficient of variation (CV),
      and average real variability (ARV). RESULTS: Compared with those without CKD, a
      lower proportion of CKD patients were dippers (51.9 versus 39.6%; P < 0.001).
      Across CKD stages, a progressive decrease in dipper (from 39.1 to 20.4%; P <
      0.001) and increase in riser proportion (from 12.3 to 36.7%; P < 0.001) were
      noted. Patients with CKD had significantly higher SBP SD, wSD, CV and ARV and
      lower DBP SD compared with those without CKD (P < 0.001). Within CKD Stages, an
      increasing trend from Stage 1 towards Stage 5 was observed for SBP SD (from 13.8
      +/- 3.7 to 15.6 +/- 5.4 mmHg), wSD (from 12.0 +/- 3.2 to 13.9 +/- 5.1 mmHg), CV
      (from 10.4 +/- 2.7 to 11.5 +/- 4.1%), ARV (from 9.9 +/- 2.3 to 11.4 +/- 3.2
      mmHg); P < 0.001 for all comparisons. DBP SD (P < 0.001), wSD and ARV (P = 0.002)
      were slightly decreasing, whereas DBP CV increased from Stage 1 to Stage 4 (P <
      0.001). In multivariate analysis, male gender, older age, abdominal obesity,
      diabetes, number of antihypertensive medications, and clinic SBP were independent
      factors for higher SBP 24-h ARV in CKD. CONCLUSION: An increase in short-term SBP
      variability was present with advancing CKD stages in a large cohort. This
      increased SBP-variability may be involved in the sharp elevation of
      cardiovascular risk with worsening renal function.

PMID- 29465711
TI  - Relation of blood pressure and organ damage: comparison between feasible,
      noninvasive central hemodynamic measures and conventional brachial measures.
AB  - OBJECTIVE: The present cross-sectional study investigated whether central SBP and
      pulse pressure (PP) measured noninvasively with a novel cuff-based stand-alone
      monitor are more strongly associated with hypertensive end-organ damage than
      corresponding brachial measures. METHODS: We investigated the cross-sectional
      association of central versus brachial SBP and PP with echocardiographic left
      ventricular mass index (LVMI), LV hypertrophy (LVH), carotid intima-media
      thickness (IMT), and increased IMT (IMT >= 75th percentile) among 246
      participants drawn from the general population (mean age 57.2 years, 55.3%
      women). RESULTS: All blood pressure (BP) measures were positively correlated with
      LVMI and IMT (P < 0.001 for all). Brachial and central SBP correlated equally
      strongly with LVMI (r = 0.42 versus 0.40, P for difference 0.19) and IMT (r =
      0.32 versus 0.33, P = 0.60). However, brachial PP correlated more strongly than
      central PP with LVMI (r = 0.34 versus 0.27, P = 0.03) and IMT (r = 0.40 versus
      0.35, P = 0.04). In multivariable-adjusted logistic models, all four BP measures
      were significantly associated with LVH and increased IMT (P <= 0.03 for all).
      However, the diagnostic accuracy of logistic regression models that included
      brachial or central hemodynamic parameters was similar for LVH [area under curve
      (AUC) for SBP: 0.74 versus 0.76, P = 0.16; AUC for PP: 0.75 versus 0.73, P =
      0.35] and IMT (AUC for SBP: 0.61 versus 0.61, P = 0.67; AUC for PP: 0.63 versus
      0.61, P = 0.29). CONCLUSION: Our findings suggest that central SBP and PP
      measured with a stand-alone noninvasive BP monitor do not improve diagnostic
      accuracy for end-organ damage over corresponding brachial measures.

PMID- 29465712
TI  - Ambulatory arterial stiffness index as a predictor of blood pressure response to
      renal denervation.
AB  - BACKGROUND: Renal denervation (RDN) can reduce blood pressure (BP) in patients
      with resistant hypertension, but less so in patients with isolated systolic
      hypertension. A possible explanation is that patients with stiffer arteries may
      have lesser neural contribution to their hypertension. METHOD: We hypothesized
      that arterial stiffness predicts the response to RDN. From ambulatory BP
      monitoring (ABPM), ambulatory arterial stiffness index (AASI) was calculated as 1
      - the regression slope of DBP versus SBP. RESULTS: In 111 patients with resistant
      hypertension, RDN reduced office and 24-h SBP after 3, 6, and 12 months (by -11
      +/- 22, -11 +/- 25, -14 +/- 21 mmHg for office, and -4 +/- 11, -5 +/- 12, -5 +/-
      15 mmHg for 24-h SBP, respectively, P < 0.01). Patients with baseline AASI above
      the median (>0.51) showed no change in 24-h SBP at 6 months after RDN (-0.4 +/-
      12.3 mmHg, P > 0.05), whereas an AASI below 0.51was associated with a marked
      reduction (-9.3 +/- 11.0 mmHg, P < 0.01). Across AASI quartiles, patients in the
      highest quartile (AASI >= 0.60) had lower muscle sympathetic nerve activity than
      the other three quartiles (39 +/- 13 versus 49 +/- 13 bursts/min, P = 0.035). The
      responder rate, defined as a 24-h SBP reduction of at least 5% was 58% in the
      lowest AASI quartile (<0.45) and 16% in the highest quartile (>=0.60). After
      adjustment for age, sex, BMI, office and 24-h SBP, an AASI less than
      0.51predicted those who respond to RDN (odds ratio 3.46, P = 0.04). CONCLUSION:
      We conclude that in patients with resistant hypertension, a lower AASI is an
      independent predictor of the BP response to RDN, possibly explained by a more
      pronounced neurogenic rather than biomechanical contribution to their BP
      elevation.

PMID- 29465713
TI  - Hydrochlorothiazide and alternative diuretics versus renin-angiotensin system
      inhibitors for the regression of left ventricular hypertrophy: a head-to-head
      meta-analysis.
AB  - BACKGROUND: Found in 36-41% of hypertension, elevated left ventricular mass (LVM)
      independently predicts cardiovascular events and total mortality. Conversely,
      drug-induced regression of LVM predicts improved outcomes. Previous studies have
      favored renin-angiotensin system inhibitors (RASIs) over other antihypertensives
      for reducing LVM but ignored differences among thiazide-type diuretics. From
      evidence regarding potency, cardiovascular events, and electrolytes, we
      hypothesized a priori that 'CHIP' diuretics [CHlorthalidone, Indapamide and
      Potassium-sparing Diuretic/hydrochlorothiazide (PSD/HCTZ)] would rival RASIs for
      reducing LVM. METHOD AND RESULTS: Systematic review yielded 12 relevant double
      blind randomized trials. CHIPs were more closely associated with reduced LVM than
      HCTZ (P = 0.004), indicating that RASIs must be compared with each diuretic
      separately. Publication bias favoring RASIs was corrected by cumulative analysis.
      For reducing LVM, HCTZ tended to be less effective than RASIs. However, the
      following surpassed RASIs: chlorthalidone Hedge's G: -0.37 (95% CI -0.72 to 
      0.02), P = 0.036; indapamide -0.20 (-0.39 to -0.01), P = 0.035; all CHIPs
      combined (with 61% of patients in one trial) -0.25 (-0.41to -0.09), P = 0.002.
      Statistical significance (P < 0.05) did not depend on any one trial. CHIPs
      reduction in LVM was 37% greater than that from RASIs. CHIPs superiority tended
      to increase with trial duration, from a negligible effect at 0.5 year to a
      maximal effect at 0.9-1.0 years: -0.26 (-0.43 to -0.09), P = 0.003. Fifty-eight
      percent of patients had information on echocardiographic components of LVM:
      relative to RASIs, CHIPs significantly reduced end-diastolic LV internal
      dimension (EDLVID): -0.18 (-0.36 to -0.00), P = 0.046. Strength of evidence
      favoring CHIPs over RASIs was at least moderate. CONCLUSION: In these novel
      results in patients with hypertension, CHIPs surpassed RASIs for reducing LVM and
      EDLVID.

PMID- 29465714
TI  - Preeclampsia induced by STOX1 overexpression in mice induces intrauterine growth
      restriction, abnormal ultrasonography and BOLD MRI signatures.
AB  - BACKGROUND: Preeclampsia is a major hypertensive disease caused by pregnancy,
      inducing proteinuria and increased blood pressure starting from the second half
      of pregnancy (early preeclampsia) or near the end of pregnancy (late
      preeclampsia). Pre-symptomatic diagnosis would allow for therapeutic
      interventions, such as with low-dose aspirin. Among non-invasive methods to
      explore organ physiology, Doppler ultrasonography (US) and functional blood
      oxygenation level-dependent (BOLD) MRI (which do not need radioactive contrast
      agents such as gadolinium) can be used in pregnant women. METHODS: In this study,
      we used US and BOLD MRI to finely characterize the phenotype of preeclampsia
      induced by the foeto-placental overexpression of the transcription factor
      storkhead box 1A (STOX1A) in female mice. RESULTS: We could observe late fetal
      growth restriction consistent with the placental dysfunction revealed by US and
      the known association between preeclampsia and intra-uterine growth restriction.
      On US, uterine and umbilical artery as well as heart and kidney parameters were
      modified in preeclamptic mice. On BOLD MRI, mean T2* values revealed considerable
      differences between control and preeclamptic placentas, which suggests altered
      dynamics of oxygen release and ratio of oxyhemoglobin to deoxyhemoglobin in the
      model. CONCLUSION: These preliminary pre-clinical results suggest that BOLD MRI
      could be evaluated as a prognostic/diagnostic tool for preeclampsia.

PMID- 29465715
TI  - Application of strict criteria in adrenal venous sampling increases the
      proportion of missed patients with unilateral disease who benefit from surgery
      for primary aldosteronism.
AB  - OBJECTIVES: Adrenal vein sampling (AVS) is intended to confirm unilateral forms
      of primary aldosteronism, which are amenable to surgical cure. Excessively strict
      AVS criteria to define lateralization may result in many patients incorrectly
      categorized as bilateral primary aldosteronism and opportunity for surgical cure
      missed. METHODS: Retrospective review of an AVS-primary aldosteronism database in
      which surgical cases are verified by standardized outcomes. Having used 'less
      strict' AVS criteria for lateralization, we examined the distribution of AVS
      lateralization indices in our confirmed unilateral primary aldosteronism cases
      both with and without cosyntropin stimulation. The proportion of proven
      unilateral cases that would have been missed with stricter AVS interpretation
      criteria was calculated. Particular focus was given to the proportion of missed
      cases according to use of international guidelines. False-positive lateralization
      with 'less strict' interpretation was also calculated. RESULTS: Of 80 surgical
      primary aldosteronism cases, 10-23% would have been missed with AVS
      lateralization indices of 3 : 1 to 5 : 1, with or without cosyntropin. If strict
      selectivity indices (for confirmation of catheterization) were combined with
      strict lateralization indices, up to 70% of unilateral primary aldosteronism
      cases could have been missed. Use of Endocrine Society AVS guidelines would have
      missed 21-43% of proven unilateral cases. 'Less strict' AVS interpretation
      yielded one case (1.2%) of false lateralization. CONCLUSION: Excessively strict
      AVS interpretation criteria will result in a high rate of missed unilateral
      primary aldosteronism with subsequent loss of opportunity for intervention. Use
      of more lenient lateralization criteria will improve the detection rate of
      unilateral primary aldosteronism with very low false-positive rate.

PMID- 29465716
TI  - Correction: The optimal time of initiation of renal replacement therapy in acute
      kidney injury: A meta-analysis.
AB  - [This corrects the article DOI: 10.18632/oncotarget.17946.].

PMID- 29465717
TI  - Correction: Aliskiren therapy in hypertension and cardiovascular disease: a
      systematic review and a meta-analysis.
AB  - [This corrects the article DOI: 10.18632/oncotarget.19382.].

PMID- 29465718
TI  - Magnetorheological elastomers enabled high-sensitive self-powered tribo-sensor
      for magnetic field detection.
AB  - The monitoring of the magnetic field is the most significant process for academic
      or industrial applications. In this study, we design a self-powered magnetic
      field sensor based on the magnetorheological elastomer (MRE) and triboelectric
      nanogenerator (TENG) that can be used for both time-varying and uniform magnetic
      field (UMF) sensing. This TENG-based magnetic-field sensor (TMFS) relies on
      contact electrification and electrostatic induction of TENG to generate an
      electrical signal in response to the magnetic-induced deformation of MRE without
      using an external power supply. Enabled by the unique sensing mechanism and
      excellent magnetic-induced deformation of MRE, the TMFS exhibits a fast response
      (20 ms) and good magnetic-field sensing performance. The TMFS with 60 wt%-MRE
      shows a maximum sensitivity of 16 mV mT-1 of the magnetic field ranging from 40
      to 100 mT experimentally, and the sensitivity and detection range of TMFS can be
      adjusted by several parameters of the device. Besides the contribution to the
      effective detection of UMF, this novel sensor provides a new idea for the
      magnetic-field measurements in self-powered mode.

PMID- 29465719
TI  - Electrocatalytic oxidation of ethanol and ethylene glycol on cubic, octahedral
      and rhombic dodecahedral palladium nanocrystals.
AB  - Cubic, octahedral and rhombic dodecahedral Pd nanocrystals were synthesized and
      examined as nanocatalysts for electro-oxidation of ethanol and ethylene glycol.
      Combined electrochemical measurements and density functional theory calculations
      reveal that nanofacet-dependent affinity and reactivity of OHads and COads are
      closely linked to the C2 alcohol oxidation activities, with the highest
      reactivity found on the Pd nanocubes bounded by {100} facets.

PMID- 29465721
TI  - 1,5-Cyclooctadienyl alcohols and ketones generate a new class of COD Pt
      complexes.
AB  - A variety of new racemic alcohol and ketone cyclooctadiene derivatives was
      prepared for their complexation with platinum to generate a new class of
      platinum(ii) complexes.

PMID- 29465722
TI  - Formation of n-n type heterojunction-based tin organic-inorganic hybrid
      perovskite composites and their functions in the photocatalytic field.
AB  - MASnI3/TiO2 composites (MA represents CH3NH3+) are prepared via a solvothermal
      method and characterized by various techniques. The results indicate that n-n
      type heterojunction structures and different ohmic contact interfaces are formed
      for the composites with different contents of MASnI3 and TiO2 before and after
      calcination, resulting in different optical and photocatalytic performances.
      Generally speaking, n-n type heterojunctions play roles in photocatalytic
      applications through two different mechanisms: the heterojunction mechanism and
      the Z-type mechanism. The calcined composites with better ohmic contact
      interfaces mainly follow the Z-type mechanism, which can promote direct radiative
      recombination of photogenerated carriers. As a result, higher luminous
      intensities and interface recombination instead of bulk recombination between
      electrons and holes can be achieved, which improves the photoluminescence and
      photocatalytic activities of the materials. Moreover, the n-n type heterojunction
      structure avoids p-type defect states to some degree, which averts the hydrolysis
      and oxidation of MASnI3 in atmosphere and enhances the long-term stability of the
      MASnI3/TiO2 composites.

PMID- 29465723
TI  - Programmable DNA switches and their applications.
AB  - DNA switches are ideally suited for numerous nanotechnological applications, and
      increasing efforts are being directed toward their engineering. In this review,
      we discuss how to engineer these switches starting from the selection of a
      specific DNA-based recognition element, to its adaptation and optimisation into a
      switch, with applications ranging from sensing to drug delivery, smart materials,
      molecular transporters, logic gates and others. We provide many examples
      showcasing their high programmability and recent advances towards their real life
      applications. We conclude with a short perspective on this exciting emerging
      field.

PMID- 29465724
TI  - Interaction anisotropy and the KPZ to KPZQ transition in particle deposition at
      the edges of drying drops.
AB  - The deposition process at the edge of evaporating colloidal drops varies with the
      shape of suspended particles. Experiments with prolate ellipsoidal particles
      suggest that the spatiotemporal properties of the deposit depend strongly on
      particle aspect ratio. As the aspect ratio increases, the particles form less
      densely-packed deposits and the statistical behavior of the deposit interface
      crosses over from the Kardar-Parisi-Zhang (KPZ) universality class to another
      universality class which was suggested to be consistent with the KPZ plus
      quenched disorder. Here, we numerically study the effect of particle interaction
      anisotropy on deposit growth. In essence, we model the ellipsoids, at the
      interface, as disk-like particles with two types of interaction patches that
      correspond to specific features at the poles and equator of the ellipsoid. The
      numerical results corroborate experimental observations and further suggest that
      the deposition transition can stem from interparticle interaction anisotropy.
      Possible extensions of our model to other systems are also discussed.

PMID- 29465725
TI  - O-Difluorodeuteromethylation of phenols using difluorocarbene precursors and
      deuterium oxide.
AB  - The first O-difluorodeuteromethylation of phenols using commercial diethyl
      bromodifluoromethylphosphonate and deuterium oxide to prepare various
      difluorodeuteromethyl aryl ethers is reported. This facile method affords a
      convenient way to introduce OCF2D groups into organic molecules.

PMID- 29465726
TI  - A Au monolayer on WC(0001) with unexpected high activity towards CO oxidation.
AB  - Catalysts with weak adsorption yet high reactivity towards CO are urgently
      required to solve the serious problem of CO poisoning that occurs in many
      important reactions, e.g., in fuel cells. Using the combination of density
      functional calculations and ab initio molecular dynamic simulations, we found a
      promising electrocatalyst for this purpose: a Au monolayer on WC(0001) (AuML/WC),
      which has both high oxygen reduction activity and high tolerance to CO poisoning.
      The advantages of using AuML/WC as an electrocatalyst in fuel cells are
      demonstrated through analyses of energetics of different reaction steps as well
      as interaction properties of reactants and products. We anticipate that the
      present results are useful to advance the development of efficient catalysts with
      high tolerance to CO poisoning.

PMID- 29465727
TI  - Nucleophilic trifluoromethylthiolation of bromoalkynones with AgSCF3: C(sp)-SCF3
      bond formation towards ynonyl trifluoromethyl sulfides.
AB  - An AgSCF3 mediated nucleophilic trifluoromethylthiolation reaction for C(sp)-SCF3
      bond formation is reported. This nucleophilic trifluoromethylthiolation reaction
      of bromoalkynones afforded various useful ynonyl trifluoromethyl sulfides in high
      yields. Interestingly, the over-addition of AgSCF3 is avoided in our approach.

PMID- 29465728
TI  - A novel class of one-dimensional Ta4TMTe4 (TM = Cr, Fe, Co and Ni) compounds with
      strain-switched magnetic states.
AB  - The development of one-dimensional (1D) nanowires with controllable magnetic
      properties is important for spintronic applications. Herein, we systematically
      investigated the structural, electronic, and magnetic properties of 1D transition
      metal (TM) compounds (Ta4TMTe4, TM = Cr, Fe, Co and Ni) through density
      functional theory (DFT) calculations. Ta4CrTe4 and Ta4FeTe4 are non-magnetic,
      while Ta4CoTe4 and Ta4NiTe4 are predicted to have antiferromagnetic ground
      states. Interestingly, uniaxial strain can induce nonmagnetism-ferromagnetism and
      nonmagnetism-antiferromagnetism transitions in Ta4CrTe4 and Ta4FeTe4 nanowires,
      respectively. Moreover, the antiferromagnetic ground states in Ta4CoTe4 and
      Ta4NiTe4 can be switched to ferromagnetic states through moderate strain. These
      strain-dependent magnetic moment and magnetic coupling transitions are related to
      the redistribution of d states in TM atoms. Our findings suggest a new route for
      facilitating the design of nanoelectronics and spintronics.

PMID- 29465729
TI  - Ballistic impact response of lipid membranes.
AB  - Therapeutic agent loaded micro and nanoscale particles as high-velocity
      projectiles can penetrate cells and tissues, thereby serving as gene and drug
      delivery vehicles for direct and rapid internalization. Despite recent progress
      in developing micro/nanoscale ballistic tools, the underlying biophysics of how
      fast projectiles deform and penetrate cell membranes is still poorly understood.
      To understand the rate and size-dependent penetration processes, we present
      coarse-grained molecular dynamics simulations of the ballistic impact of
      spherical projectiles on lipid membranes. Our simulations reveal that upon
      impact, the projectile can pursue one of three distinct pathways. At low
      velocities below the critical penetration velocity, projectiles rebound off the
      surface. At intermediate velocities, penetration occurs after the projectile
      deforms the membrane into a tubular thread. At very high velocities, rapid
      penetration occurs through localized membrane deformation without tubulation.
      Membrane tension, projectile velocity and size govern which phenomenon occurs,
      owing to their positive correlation with the reaction force generated between the
      projectile and the membrane during impact. Two critical membrane tension values
      dictate the boundaries among the three pathways for a given system, due to the
      rate dependence of the stress generated in the membrane. Our findings provide
      broad physical insights into the ballistic impact response of soft viscous
      membranes and guide design strategies for drug delivery through lipid membranes
      using micro/nanoscale ballistic tools.

PMID- 29465731
TI  - Compact layer free mixed-cation lead mixed-halide perovskite solar cells.
AB  - Thickness-tunable and compact FA0.83Cs0.17Pb(I0.6Br0.4)3 perovskite thin films
      are achieved with a large grain size up to 12 microns. They are then employed to
      fabricate functional solar cells with a simplified planar structure without the
      use of electron-transport (ETL) layers. These results are highly encouraging for
      the future large-scale fabrication of FA0.83Cs0.17Pb(I0.6Br0.4)3-based solar
      cells.

PMID- 29465730
TI  - Dihomo-gamma-linolenic acid induces fat loss in C. elegans in an omega-3
      independent manner by promoting peroxisomal fatty acid beta-oxidation.
AB  - Bioactive compounds, including some fatty acids (FAs), can induce beneficial
      effects on body fat-content and metabolism. In this work, we have used C. elegans
      as a model to examine the effects of several FAs on body fat accumulation. Both
      omega-3 and omega-6 fatty acids induced a reduction of fat content in C. elegans,
      with linoleic, gamma-linolenic and dihomo-gamma-linolenic acids being the most
      effective ones. These three FAs are sequential metabolites especially in omega-6
      PUFA synthesis pathway and the effects seem to be primarily due to dihomo-gamma
      linolenic acid, and independent of its transformation into omega-3 or arachidonic
      acid. Gene expression analyses suggest that peroxisomal beta oxidation is the
      main mechanism involved in the observed effect. These results point out the
      importance of further analysis of the activity of these omega-6 FAs, due to their
      potential application in obesity and related diseases.

PMID- 29465734
TI  - Refining the aggregate exposure pathway.
AB  - Advancements in measurement technologies and modeling capabilities continue to
      result in an abundance of exposure information, adding to that currently in
      existence. However, fragmentation within the exposure science community acts as
      an obstacle for realizing the vision set forth in the National Research Council's
      report on Exposure Science in the 21st century to consider exposures from source
      to dose, on multiple levels of integration, and to multiple stressors. The
      concept of an Aggregate Exposure Pathway (AEP) was proposed as a framework for
      organizing and integrating diverse exposure information that exists across
      numerous repositories and among multiple scientific fields. A workshop held in
      May 2016 followed introduction of the AEP concept, allowing members of the
      exposure science community to provide extensive evaluation and feedback regarding
      the framework's structure, key components, and applications. The current work
      briefly introduces topics discussed at the workshop and attempts to address key
      challenges involved in refining this framework. The resulting evolution in the
      AEP framework's features allows for facilitating acquisition, integration,
      organization, and transparent application and communication of exposure knowledge
      in a manner that is independent of its ultimate use, thereby enabling reuse of
      such information in many applications.

PMID- 29465735
TI  - Ni-catalyzed two-component reductive dicarbofunctionalization of alkenes via
      radical cyclization.
AB  - A reductive dicarbofunctionalization reaction of alkenes has been developed and
      applied to the preparation of substituted carbo- and heterocycles. The reaction
      conditions avoid the use of air-sensitive organometallic reagents, and are
      compatible with a broad range of bromo-electrophiles and a wide variety of
      substituents to give cyclic products in excellent yields.

PMID- 29465736
TI  - Fermentation of non-digestible raffinose family oligosaccharides and
      galactomannans by probiotics.
AB  - Due to their prebiotic potential indigestible oligosaccharides became a major
      focus of research interest. In this study the growth of selected probiotic
      strains including lactobacilli, bifidobacteria, Lactococcus lactis, Streptococcus
      salivarius ssp. thermophilus, Pediococcus ssp. and Enterococcus faecium with the,
      raffinose family oligosaccharides (RFOs) raffinose, stachyose and verbascose and
      galactomannan from guar bean Cyamopsis tetragonoloba (total guar carbohydrates,
      oligosaccharides (dp 2-4) and polysaccharides (dp > 5), obtained by size
      exclusion chromatography) were tested by means of turbidity measurements. RFOs
      were used by 75% of all strains, with some delay for the trisaccharide raffinose
      and the tetrasaccharide stachyose and a limited fermentation of the
      pentasaccharide verbascose. L. reuteri, P. pentosaceus and B. lactis HNO19TM were
      able to ferment not only raffinose and stachyose but also verbascose. Guar
      oligosaccharides were fermented by 15 out of 20 strains; P. acidilactici, L.
      acidophilus, L. rhamnosus GG and B. animalis ssp. lactis BB12 metabolized them
      comparably well as glucose or galactose. Isolated guar polysaccharides were not
      fermented whereas total guar carbohydrates were fermented by 7 strains,
      apparently caused by the oligosaccharide content. The findings of this study may
      be important for functional food products especially for indigestible
      oligosaccharides which may cause adverse effects in the gut when not cleaved.

PMID- 29465737
TI  - A novel panchromatic shutter based on an ambipolar electrochromic system without
      supporting electrolyte.
AB  - Two triphenylamine derivatives, N,N,N',N'-tetrakis(4-methoxyphenyl)-1,4
      phenylenediamine TPPA and N,N,N',N'-tetrakis(4-methoxyphenyl)-1,1'-biphenyl-4,4'
      diamine TPB, were successfully prepared and combined with HV to fabricate the
      electrochromic device as a panchromatic shutter for the application of
      transparent display. The obtained electrochromic device exhibits exceptional
      novel electrochromic properties, including enhanced color contrast, switching
      time, and long-term stability. Furthermore, it is worth mentioning that the most
      important contribution of this ambipolar system approach is that no supporting
      electrolyte is added into the device.

PMID- 29465738
TI  - Positional accuracy of geocoding from residential postal codes versus full street
      addresses.
AB  - BACKGROUND: Postal codes are often the only geographic identifier available for
      assigning contextual or environmental information to a study population. This
      analysis assesses the influence of three factors-delivery mode type (mode of
      postal delivery), representative point type (source of latitude-longitude
      coordinates), and community size-on the accuracy of postal code spatial
      assignment. DATA AND METHODS: PCCF+ (Postal Code Conversion File Plus) was used
      to assign delivery mode type, representative point type and community size to
      each individual in the 2011 Census of Canada. A sample (n = 1,004) was randomly
      selected with a minimum of 90 observations for each category of those three
      factors. Based on the address information of individuals in the sample, measures
      of positional accuracy for geocoding from residential postal codes (PCCF+) versus
      reference locations as determined by full street addresses (Google Maps) were
      calculated using a geographic information system. Accuracy was measured as the
      distance that the geocoded position differed from the full street address.
      RESULTS: Positional accuracy was related primarily to mode of postal delivery.
      Rural and mixed (partly urban, partly rural) modes had much higher geocoding
      error than did urban modes. Rural and small-town Canada and latitude and
      longitude based on dissemination area centroids had low accuracy, largely because
      of their close relationship to rural and mixed modes of delivery. DISCUSSION: The
      accuracy of geocoding from postal codes can vary. Geocoding imprecision may
      result in misclassification, depending on the spatial resolution of the
      environmental or contextual measures. The spatial resolution required for a study
      helps to identify subpopulations that should be excluded because of inadequate
      positional accuracy.

PMID- 29465739
TI  - Analysis of trends in the prevalence of cannabis use in Canada, 1985 to 2015.
AB  - BACKGROUND: The Canadian federal government has committed to legalize, regulate,
      and restrict non-medical cannabis use by adults in 2018. To prepare for
      monitoring the health, social and economic impacts of this policy change, a
      greater understanding of the long-term trends in the prevalence of cannabis use
      in Canada is needed. DATA AND METHODS: Nine national surveys of the household
      population collected information about cannabis use during the period from 1985
      through 2015. These surveys are examined for comparability. The data are used to
      estimate past-year (current) cannabis use (total, and by sex and age). Based on
      the most comparable data, trends in use from 2004 through 2015 are estimated.
      RESULTS: From 1985 through 2015, past-year cannabis use increased overall.
      Analysis of comparable data from the Canadian Tobacco Use Monitoring Survey and
      the Canadian Tobacco, Alcohol and Drugs Survey for the 2004-to-2015 period
      suggests that use was stable among 15- to 17-year-old males, decreased among 15-
      to 17-year-old females and among 18- to 24-year-olds (both sexes), and increased
      among people aged 25 or older. DISCUSSION: According to data from national
      population surveys, since 2004, cannabis use was stable or decreased among youth,
      and rose among adults. Results highlight the importance of consistent monitoring
      of use in the pre-and post-legalization periods.

PMID- 29465740
TI  - A Technical Guide for Fiber Tract Dissection of the Internal Capsule.
AB  - AIM: Dissection of white fibers is important in identifying detailed
      neuroanatomical relationships. With tractrography it is possible to transport and
      apply this knowledge in a practical way to treat many diseases involving the
      white matter. MATERIAL AND METHODS: The Klingler method, subsequently
      disseminated by Ture with slight modifications was used. RESULTS: We review some
      historical aspects of white fibers and provide a guide for dissection of the
      internal capsule. The removal of gray matter allowed us to obtain a view of the
      white matter. We removed all U-shaped fibers to expose the insular cortex. The
      cortex of the insular lobe was removed, which exposed the extreme capsule. The
      removal of the claustrum exposed the external capsule, which covers the lentiform
      nucleus, specifically the putamen. During dissection, removing some fibers of the
      external capsule produced windows in which the putamen could be medially
      visualized. Since the internal capsule lies medial to the lentiform nucleus, it
      was necessary to remove the nucleus in order to expose the internal capsule. We
      identified five regions of the internal capsule: the anterior limb, genu,
      posterior limb, and sublenticular and retrolenticular parts. Finally, we
      determined that the fibers of the corona radiata condense into the internal
      capsule at the level of the superior border of the lentiform nucleus. CONCLUSION:
      Knowledge gained with the cadaveric fiber dissection technique can be applied in
      microsurgical practice and can be used to evaluate the surgical treatment for
      different tumors and vascular malformations.

PMID- 29465741
TI  - Management of Hardware Related Infections after DBS Surgery: A Cost Analysis.
AB  - AIM: To investigate the costs of treating the infection with antibiotics only
      with the risk of surgery when unsuccessful versus immediate removal followed by
      re-implantation in patients with deep brain stimulation (DBS) hardware infection.
      MATERIAL AND METHODS: We calculated the costs of the different strategies through
      a standard costing procedure. A decision model has been applied to establish the
      average treatment cost per patient representative for a clinical setting where
      both strategies are employed. Subsequently, a sensitivity analysis has been
      performed to assess the influence of clinical assumptions regarding the
      effectiveness of antibiotics treatment on average treatment costs. RESULTS: The
      costs of treating a case of DBS hardware infection with immediate internal pulse
      generator (IPG) replacement surgery were ?29,301 compared to ?9499 for successful
      antibiotic treatment. For antibiotic treatment followed by IPG replacement
      surgery the total costs were ?38,741. Antibiotic treatment alone was successful
      in 44% (4/9) of the included cases of DBS infection, resulting in average
      treatment costs per patient of ?25,745. Trying to resolve DBS hardware infections
      initially with antibiotics reduced treatment costs by 12.1%. CONCLUSION:
      Treatment with antibiotics with the risk of a later removal when unsuccessful was
      a more valuable strategy in terms of costs when compared to immediate surgical
      intervention in cases of hardware-related infections in DBS surgeries.

PMID- 29465742
TI  - Endoscopic Management of Intraventricular Neurocysticercosis.
AB  - Objective Restoration of CSF flow and removal of Intraventricular Cystecercal
      Cyst is the main goal in treatment Hydrocephalus due Intraventricular
      Neurocysticercosis. The purpose of this study was to evaluate the technique and
      outcome of Endoscopic management of Intraventricular Neurocysticercosis. Methods
      We retrospectively analysed the records of 30 consecutive patients of
      Intraventricular Intra third and fourth ventricle Neurocysticercosiswho underwent
      endoscopic management.The clinical profile of the patient were evaluated which
      included age, symptoms and signs. Transcranial endoscopy was perfomed through
      frontal burr hole using Gaab Universal Endoscope system with rigid 0o and 30o
      telescope for ETV and removal of cyst was described. The mean follow up was 22.6
      months Results In 86.67 % (26/30) patients we are able to visualize/ excise/
      decompress the cyst. We were able to successfully excise all the third
      ventricular cysts (16/16) and in 66.67% (8/12) of the fourth ventricular cysts.In
      90% (27/30) patients we were able to successfully divert the CSF flow and achieve
      long term shunt free period. Conclusion We found that endoscopic CSF diversion in
      cases of Intraventricular NCC is feasible and associated with high success rate.
      Endoscopic CSF diversion in NCC related hydrocephalus usually produces a long
      term cure.

PMID- 29465743
TI  - Participation in bowel screening among men attending abdominal aortic aneurysm
      screening.
AB  - BACKGROUND: Uptake of population-based screening for colorectal cancer in
      Scotland is around 55 per cent. Abdominal aortic aneurysm (AAA) screening has
      recently been introduced for men aged 65 years and the reported uptake is 78 per
      cent. The aim was to determine the impact of a brief intervention on bowel
      screening in men who attended AAA screening, but previously failed to complete
      bowel screening. METHODS: Men invited for AAA screening between September 2015
      and March 2016 within NHS Tayside were included. Attendees who had not responded
      to their latest bowel screening invitation were seen by a colorectal cancer
      clinical nurse specialist. Reasons for not completing the faecal occult blood
      test (FOBT) were recorded; brief information on colorectal cancer screening was
      communicated, and participants were offered a further invitation to complete a
      FOBT. Those who responded positively were sent a further FOBT from the Scottish
      Bowel Screening Centre. Subsequent return of a completed FOBT within 6 months was
      recorded. RESULTS: A total of 556 men were invited for AAA screening, of whom
      38.1 per cent had not completed a recent FOBT. The primary reason stated for not
      participating was the time taken to complete the test or forgetting it (35.1 per
      cent). Other reasons included: lack of motivation (23.4 per cent), confusion
      regarding the aim of screening (16.2 per cent), disgust (19.8 per cent), fear
      (6.3 per cent) and other health problems (9.9 per cent). Following discussion,
      81.1 per cent agreed to complete the FOBT and 49 per cent subsequently returned
      the test. CONCLUSION: A substantial proportion of previous bowel screening non
      responders subsequently returned a completed FOBT following a brief intervention
      with a nurse specialist. Attendance at non-bowel screening appointments may
      provide a valuable opportunity to improve bowel screening uptake.

PMID- 29465744
TI  - Baseline factors predicting a response to neoadjuvant chemotherapy with
      implications for non-surgical management of triple-negative breast cancer.
AB  - BACKGROUND: Patients with triple-negative breast cancer (TNBC) and a pathological
      complete response (pCR) after neoadjuvant chemotherapy may be suitable for non
      surgical management. The goal of this study was to identify baseline
      clinicopathological variables that are associated with residual disease, and to
      evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal
      carcinoma in situ (DCIS) components in TNBC. METHODS: Patients with TNBC treated
      with neoadjuvant chemotherapy followed by surgical resection were identified.
      Patients with a pCR were compared with those who had residual disease in the
      breast and/or lymph nodes. Clinicopathological variables were analysed to
      determine their association with residual disease. RESULTS: Of the 328 patients,
      36.9 per cent had no residual disease and 9.1 per cent had residual DCIS only.
      Patients with residual disease were more likely to have malignant
      microcalcifications (P = 0.023) and DCIS on the initial core needle biopsy (CNB)
      (P = 0.030). Variables independently associated with residual disease included:
      DCIS on CNB (odds ratio (OR) 2.46; P = 0.022), T2 disease (OR 2.40; P = 0.029),
      N1 status (OR 2.03; P = 0.030) and low Ki-67 (OR 2.41; P = 0.083). Imaging after
      neoadjuvant chemotherapy had an accuracy of 71.7 (95 per cent c.i. 66.3 to 76.6)
      per cent and a negative predictive value of 76.9 (60.7 to 88.9) per cent for
      identifying residual disease in the breast and lymph nodes. Neoadjuvant
      chemotherapy did not eradicate the DCIS component in 55 per cent of patients.
      CONCLUSION: The presence of microcalcifications on imaging and DCIS on initial
      CNB are associated with residual disease after neoadjuvant chemotherapy in TNBC.
      These variables can aid in identifying patients with TNBC suitable for inclusion
      in trials evaluating non-surgical management after neoadjuvant chemotherapy.

PMID- 29465745
TI  - Deserving citizenship? Exploring migrants' experiences of the 'citizenship test'
      process in the United Kingdom.
AB  - Since the early 2000s several European countries have introduced language and
      citizenship tests as new requirements for access to long-term residence or
      naturalization. The content of citizenship tests has been often presented as
      exclusionary in nature, in particular as it is based on the idea that access to
      citizenship has to be 'deserved'. In this paper, we aim to explore the
      citizenship tests 'from below', through the focus on the experience of migrants
      who prepare and take the 'Life in the UK' test, and with particular reference to
      how they relate to the idea of 'deservingness'. Through a set of in-depth
      interviews with migrants in two different cities (Leicester and London), we show
      that many of them use narratives in which they distinguish between the 'deserving
      citizens' and the 'undeserving Others' when they reflect upon their experience of
      becoming citizens. In so doing, they negotiate new hierarchies of inclusion into
      and exclusion from citizenship, which reflect broader neo-liberal and ethos-based
      conceptions of citizenship.

PMID- 29465746
TI  - Using textbook outcome as a measure of quality of care in oesophagogastric cancer
      surgery.
AB  - BACKGROUND: Textbook outcome is a multidimensional measure representing an ideal
      course after oesophagogastric cancer surgery. It comprises ten perioperative
      quality-of-care parameters and has been developed recently using population-based
      data. Its association with long-term outcome is unknown. The objectives of this
      study were to validate the clinical relevance of textbook outcome at a hospital
      level, and to assess its relation with long-term survival after treatment for
      oesophagogastric cancer. METHODS: All patients with oesophageal or gastric cancer
      scheduled for surgery with curative intent between January 2009 and June 2015
      were selected from an institutional database. A Cox model was used to study the
      association between textbook outcome and survival. RESULTS: A textbook outcome
      was achieved in 58 of 144 patients (40.3 per cent) with oesophageal cancer and in
      48 of 105 (45.7 per cent) with gastric cancer. Factors associated with not
      achieving a textbook outcome were failure to achieve a lymph node yield of at
      least 15 (after oesophagectomy) and postoperative complications of grade II or
      more. After oesophagectomy, median overall survival was longer for patients with
      a textbook outcome than for patients without (median not reached versus 33
      months; P = 0.012). After gastrectomy, median survival was 54 versus 33 months
      respectively (P = 0.018). In multivariable analysis, textbook outcome was
      associated with overall survival after oesophagectomy (hazard ratio 2.38, 95 per
      cent c.i. 1.29 to 4.42) and gastrectomy (hazard ratio 2.58, 1.25 to 5.32).
      CONCLUSION: Textbook outcome is a clinically relevant measure in patients
      undergoing oesophagogastric cancer surgery as it can identify underperforming
      parameters in a hospital setting. Overall survival in patients with a textbook
      outcome is better than in patients without a textbook outcome.

PMID- 29465747
TI  - Antibiotics for treating gonorrhoea in pregnancy.
AB  - BACKGROUND: Gonorrhoea is a sexually transmitted infection that is caused by
      Neisseria gonorrhoeae, and is a major public health challenge today. N
      gonorrhoeae can be transmitted from the mother's genital tract to the newborn
      during birth, and can cause gonococcal ophthalmia neonatorum as well as systemic
      neonatal infections. It can also cause endometritis and pelvic sepsis in the
      mother. This review updates and replaces an earlier Cochrane Review on
      antibiotics for treating this infectious condition. OBJECTIVES: To assess the
      clinical effectiveness and harms of antibiotics for treating gonorrhoea in
      pregnant women. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (31 May 2017), LILACS database (1982 to April 5, 2017),
      the WHO International Clinical Trials Registry Platform (ICTRP; April 5, 2017),
      ClinicalTrials.gov (April 5, 2017), the ISRCTN Registry (April 5, 2017), and
      Epistemonikos (April 5, 2017). We also searched reference lists of all retrieved
      articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs)
      comparing the use of antibiotics for treating gonorrhoea in pregnancy. The
      antibiotics could have been used alone or in combination, were administered
      parenterally, orally, or both, and were compared with another antibiotic.We
      included RCTs regardless of their publication status (published, unpublished,
      published as an article, an abstract, or a letter), language, or country. We
      applied no limits on the length of follow-up.We excluded RCTs using a cluster- or
      cross-over design, or quasi-RCTs. DATA COLLECTION AND ANALYSIS: Three review
      authors independently assessed trials for inclusion and risk of bias, extracted
      data, and checked them for accuracy. MAIN RESULTS: We included two RCTs, that
      randomised 514 pregnant women (347 women analysed) at a mean gestational age of
      22 weeks. Both trials were conducted in the outpatient department of the same two
      hospitals in the USA between 1993 and 2001, and had a follow-up of 14 days. One
      of the trials was sponsored by a drug company. We considered both trials to be at
      a high risk of bias.One trial compared ceftriaxone (125 mg, intramuscular) with
      cefixime (400 mg, oral); the other trial had three arms, and assessed ceftriaxone
      (250 mg, intramuscular) versus either amoxicillin (3 g, oral) plus probenecid (1
      g, oral) or spectinomycin (2 g, intramuscular). We did not include the
      spectinomycin data because this medication is no longer produced. We were unable
      to conduct meta-analysis because the trials compared different medications.We
      found inconclusive evidence that there were clear differences in the cure of
      gonococcal infections (genital, extragenital, or both) between intramuscular
      ceftriaxone versus oral amoxicillin plus oral probenecid (risk ratio (RR) 1.07,
      95% confidence interval (CI) 0.98 to 1.16; one RCT; 168 women; very low-quality
      evidence) or intramuscular ceftriaxone versus oral cefixime (RR 0.99, 95% CI 0.91
      to 1.08; one RCT; 95 women; very low-quality evidence).Neither of the trials
      reported on two of this review's primary maternal outcomes: incidence of
      obstetric complications (miscarriage, premature rupture of membranes, preterm
      delivery, or fetal death), or disseminated gonococcal infection, or on the
      incidence of neonatorum ophthalmia in the neonates.One trial reported one case of
      vomiting in the oral amoxacillin plus probenecid group. Trials reported pain at
      the injection sites, but did not quantify it. Hyperberbilurrubinemia was more
      frequent in neonates whose mothers were exposed to ceftriaxone. There were no
      clear differences between groups for neonatal malformation. AUTHORS' CONCLUSIONS:
      This Cochrane Review found high levels of cure of gonococcal infections in
      pregnancy with the given antibiotic regimens. However, the evidence in this
      review is inconclusive as it does not support one particular regimen over
      another. This conclusion was based on very low-quality evidence (downgraded for
      poor trial design, imprecision) from two trials (involving 514 women), which we
      assessed to be at a high risk of bias for a number of domains. The harm profiles
      of the antibiotic regimes featured in this review remain unknown.High-quality
      RCTs are needed, with sufficient power to assess the clinical effectiveness and
      potential harms of antibiotics in pregnant women with gonorrhoea. These should be
      planned according to Standard Protocol Items: Recommendations for Interventional
      Trials (SPIRIT),conducted following CONSORT recommendations, and based on Patient
      Centered Outcomes Research Institute (PCORI) outcomes.

PMID- 29465748
TI  - Species associations overwhelm abiotic conditions to dictate the structure and
      function of wood-decay fungal communities.
AB  - Environmental conditions exert strong controls on the activity of saprotrophic
      microbes, yet abiotic factors often fail to adequately predict wood decomposition
      rates across broad spatial scales. Given that species interactions can have
      significant positive and negative effects on wood-decay fungal activity, one
      possibility is that biotic processes serve as the primary controls on community
      function, with abiotic controls emerging only after species associations are
      accounted for. Here we explore this hypothesis in a factorial field warming- and
      nitrogen-addition experiment by examining relationships among wood decomposition
      rates, fungal activity, and fungal community structure. We show that functional
      outcomes and community structure are largely unrelated to abiotic conditions,
      with microsite and plot-level abiotic variables explaining at most 19% of the
      total variability in decomposition and fungal activity, and 2% of the variability
      in richness and evenness. In contrast, taxonomic richness, evenness, and species
      associations (i.e., co-occurrence patterns) exhibited strong relationships with
      community function, accounting for 52% of the variation in decomposition rates
      and 73% in fungal activity. A greater proportion of positive vs. negative species
      associations in a community was linked to strong declines in decomposition rates
      and richness. Evenness emerged as a key mediator between richness and function,
      with highly even communities exhibiting a positive richness-function relationship
      and uneven communities exhibiting a negative or null response. These results
      suggest that community-assembly processes and species interactions are important
      controls on the function of wood-decay fungal communities, ultimately
      overwhelming substantial differences in abiotic conditions.

PMID- 29465750
TI  - Identification of pyrG Used as an Endogenous Reference Gene in Qualitative and
      Real-Time Quantitative PCR Detection of Pleurotus ostreatus.
AB  - : As a well-known edible fungus rich in nutrients, Pleurotus ostreatus has been
      used as an alternative to expensive wild edible fungi. Specifically, the fact
      that using P. ostreatus instead of other expensive wild edible fungi has damaged
      the rights and interests of consumers. Among the existing methods for detection
      of food adulteration, the amplification of endogenous reference gene is the most
      accurate method. However, an ideal endogenous reference gene for P. ostreatus has
      yet to be developed. In this study, a DNA extraction method for P. ostreatus was
      optimized, and pyrG was selected as a species-specific gene through sequence
      alignment. This gene was subsequently subjected to qualitative and quantitative
      Polymerase Chain Reaction (PCR) assays with 3 different P. ostreatus varieties
      and 7 other species. A low detection limit of 5 pg/MUL was obtained by TaqMan
      quantitative PCR, and no pyrG amplification product was observed in the 7 other
      species. No allelic variation was detected in P. ostreatus varieties. These
      experiments confirmed that pyrG was an ideal endogenous reference gene for the
      qualitative and real-time quantitative PCR detection of P. ostreatus. This method
      was also suitable for the examination of processed P. ostreatus samples and
      determination of adulteration in wild mushrooms. PRACTICAL APPLICATION: The pyrG
      gene was chosen as an ideal endogenous reference gene for the qualitative and
      real-time quantitative PCR detection of P. ostreatus, and the detection limit was
      5 pg/MUL for the quantification. This method is used not only for raw materials
      but also for processed P. ostreatus products and other processed mushroom foods.

PMID- 29465749
TI  - Systematic review of measurement tools to assess surgeons' intraoperative
      cognitive workload.
AB  - BACKGROUND: Surgeons in the operating theatre deal constantly with high-demand
      tasks that require simultaneous processing of a large amount of information. In
      certain situations, high cognitive load occurs, which may impact negatively on a
      surgeon's performance. This systematic review aims to provide a comprehensive
      understanding of the different methods used to assess surgeons' cognitive load,
      and a critique of the reliability and validity of current assessment metrics.
      METHODS: A search strategy encompassing MEDLINE, Embase, Web of Science,
      PsycINFO, ACM Digital Library, IEEE Xplore, PROSPERO and the Cochrane database
      was developed to identify peer-reviewed articles published from inception to
      November 2016. Quality was assessed by using the Medical Education Research Study
      Quality Instrument (MERSQI). A summary table was created to describe study
      design, setting, specialty, participants, cognitive load measures and MERSQI
      score. RESULTS: Of 391 articles retrieved, 84 met the inclusion criteria,
      totalling 2053 unique participants. Most studies were carried out in a simulated
      setting (59 studies, 70 per cent). Sixty studies (71 per cent) used self
      reporting methods, of which the NASA Task Load Index (NASA-TLX) was the most
      commonly applied tool (44 studies, 52 per cent). Heart rate variability analysis
      was the most used real-time method (11 studies, 13 per cent). CONCLUSION: Self
      report instruments are valuable when the aim is to assess the overall cognitive
      load in different surgical procedures and assess learning curves within
      competence-based surgical education. When the aim is to assess cognitive load
      related to specific operative stages, real-time tools should be used, as they
      allow capture of cognitive load fluctuation. A combination of both subjective and
      objective methods might provide optimal measurement of surgeons' cognition.

PMID- 29465751
TI  - Prognostic value of pathological lymph node status and primary tumour regression
      grading following neoadjuvant chemotherapy - results from the MRC OE02
      oesophageal cancer trial.
AB  - AIMS: Neoadjuvant chemotherapy (NAC) remains an important therapeutic option for
      advanced oesophageal cancer (OC). Pathological tumour regression grade (TRG) may
      offer additional information by directing adjuvant treatment and/or follow-up but
      its clinical value remains unclear. We analysed the prognostic value of TRG and
      associated pathological factors in OC patients enrolled in the Medical Research
      Council (MRC) OE02 trial. METHODS AND RESULTS: Histopathology was reviewed in 497
      resections from OE02 trial participants randomised to surgery (S group; n = 244)
      or NAC followed by surgery [chemotherapy plus surgery (CS) group; n = 253]. The
      association between TRG groups [responders (TRG1-3) versus non-responders (TRG4
      5)], pathological lymph node (LN) status and overall survival (OS) was analysed.
      One hundred and ninety-five of 253 (77%) CS patients were classified as 'non
      responders', with a significantly higher mortality risk compared to responders
      [hazard ratio (HR) = 1.53, 95% confidence interval (CI) = 1.05-2.24, P = 0.026].
      OS was significantly better in patients without LN metastases irrespective of TRG
      [non-responders HR = 1.87, 95% CI = 1.33-2.63, P < 0.001 versus responders HR =
      2.21, 95% CI = 1.11-4.10, P = 0.024]. In multivariate analyses, LN status was the
      only independent factor predictive of OS in CS patients (HR = 1.93, 95% CI = 1.42
      2.62, P < 0.001). Exploratory subgroup analyses excluding radiotherapy-exposed
      patients (n = 48) showed similar prognostic outcomes. CONCLUSION: Lymph node
      status post-NAC is the most important prognostic factor in patients with
      resectable oesophageal cancer, irrespective of TRG. Potential clinical
      implications, e.g. adjuvant treatment or intensified follow-up, reinforce the
      importance of LN dissection for staging and prognostication.

PMID- 29465752
TI  - Endothelial extracellular vesicles modulate the macrophage phenotype: Potential
      implications in atherosclerosis.
AB  - Endothelial cells (ECs) and macrophages engage in tight and specific interactions
      that play critical roles in cardiovascular homeostasis and the pathogenesis of
      atherosclerosis. Extracellular vesicles (EVs) are circular membrane fragments
      released from the endosomal compartment as exosomes or shed from the surfaces of
      the membranes of most cell types. Increasing evidence indicates that EVs play a
      pivotal role in cell-to-cell communication. However, the contribution of EVs, as
      determine by oxidized low-density lipoprotein (ox-LDL)-exposed and/or Kruppel
      like factor 2 (KLF2)-transduced ECs in the interaction between vascular ECs and
      monocytes/macrophages, which is a key event in atherosclerotic plaque
      development, has remained elusive. This study demonstrates the characteristic
      impact of EVs from ox-LDL-treated and/or KLF2-transduced ECs on the
      monocyte/macrophage phenotype in vitro and in vivo.Q-PCR showed that both the
      atherosclerosis inducer ox-LDL and atheroprotective factor KLF2 regulated
      inflammation-associated microRNA-155 (miR-155) expression in human umbilical vein
      endothelial cells (HUVECs). Moreover, coculture, immunofluorescence and flow
      cytometry revealed that miR-155 was enriched in ox-LDL-induced ECs-EVs and
      subsequently transferred to human monocytic THP1 cells, in which these vesicles
      enhance monocyte activation by shifting the monocytes/macrophages balance from
      anti-inflammatory M2 macrophages towards proinflammatory M1 macrophages; EVs from
      KLF2-expressing ECs suppressed monocyte activation by enhancing immunomodulatory
      responses and diminishing proinflammatory responses, which indicate the potent
      anti-inflammatory activities of these cells. Furthermore, oil red staining showed
      that atherosclerotic lesions were reduced in mice that received EVs from KLF2
      transduced ECs with decreased proinflammatory M1 macrophages and increased anti
      inflammatory M2 macrophages, and this effect is at least partly due to the
      decreased expression of inflammation-associated miR-155, confirming our in vitro
      findings. In summary, this study provides novel insights into the
      pathophysiological effects of altered EV secretion and/or microRNA content and
      their influence on modulating monocyte activation depending on the environment
      surrounding EVs-releasing ECs.

PMID- 29465753
TI  - Size and molecular weight determination of polysaccharides by means of nano
      electrospray gas-phase electrophoretic mobility molecular analysis (nES GEMMA).
AB  - Size, size distribution and molecular weight (MW) determination of nanoparticles
      and that are for example large polymers, are of great interest and pose an
      analytical challenge. In this context, nano electrospray gas-phase
      electrophoretic mobility molecular analysis (nES GEMMA) is a valuable tool with
      growing impact. Separation of single-charged analytes according to their
      electrophoretic mobility diameter (EMD) starting from single-digit EMDs up to
      several hundred nm diameters is possible. In case of spherical analytes, the EMD
      corresponds to the dry nanoparticle size. Additionally, the instrument is capable
      of number-based, single-particle detection following the recommendation of the
      European Commission for nanoparticle characterization (2011/696/EU). In case an
      EMD/MW correlation for a particular compound class (based on availability of well
      defined standards) exists, a nanoparticle's MW can be determined from its EMD. In
      the present study, we focused on nES GEMMA of linear and branched, water-soluble
      polysaccharides forming nanoparticles and were able to obtain spectra for both
      analyte classes regarding single-charged species. Based on EMDs for corresponding
      analytes, an excellent EMD/MW correlation could be obtained in case of the
      branched natural polymer (dextran). This enables the determination of dextran MWs
      from nES GEMMA spectra despite high analyte polydispersity and in a size/MW
      range, where classical mass spectrometry is limited. EMD/MW correlations based on
      linear (pullulans, oat-beta-glucans) polymers were significantly different,
      possibly indicating challenges in the exact MW determination of these compounds
      by, for example, chromatographic and light scattering means. Despite these
      observations, nES GEMMA of linear, monosaccharide-based polymers enabled the
      determination of size and size-distribution of such dry bionanoparticles.

PMID- 29465755
TI  - Comparison of the CMNC and MNC apheresis protocol for the collection of T-cells
      showed comparable outcome: An observational study in a single centre.
AB  - BACKGROUND: An increasing demand for human lymphocytes require an efficient,
      reliable and reproducible lymphocyte process. Here, we compare the Spectra
      Optia(r) CMNC protocol with the Optia MNC platform in unmobilised donor
      lymphocyte collections. PURPOSE: To establish and compare the feasibility,
      efficiency, and practicability of the two apheresis protocols. METHODS: Data was
      collected prospectively from 60 non-cytokine stimulate donors who underwent a
      total of 64 T-cell collection procedures. Of these, 24 procedures were performed
      in the CMNC cohort and 40 procedures in the MNC cohort. All donors in the CMNC
      group were related; all donors in the MNC group were donors from a registry.
      Donor characteristics, procedure parameters and cellular product content were
      analysed and compared. RESULTS: Donor characteristics and full blood count
      results were comparable, except the median white blood cell count, which was
      higher in the CMNC cohort (6.87 vs. 5.58 *109 /L, P < .005). This resulted in
      higher lymphocyte (1.95 vs. 1.57 *109 /L, P < .009) and CD3+ cell counts (1476
      vs. 1060/L, P < .02). A total blood volume processed of 2.0 resulted in i) run
      time (222 vs. 242 min), ii) product volume (192 vs. 183 ml), iii) platelet
      content (2140 vs. 1345 *106 /ml, P < .003). CD3+ CE2 (%): 54.7 vs. 50.4.
      CONCLUSION: The CMNC and MNC protocols are reliable, efficient and comparable in
      performance parameters and cell composition of final product, respectively. One
      advantages of the CMNC protocol is the potential ability to tailor the cell
      composition of the final product accordingly to demands from cell processing
      laboratories.

PMID- 29465756
TI  - A Variety of Bond Analysis Methods, One Answer? An Investigation of the Element
      Oxygen Bond of Hydroxides Hn XOH.
AB  - There is a great variety of bond analysis tools that aim to extract information
      on the bonding situation from the molecular wavefunction. Because none of these
      can fully describe bonding in all of its complexity, it is necessary to regard a
      balanced selection of complementary analysis methods to obtain a reliable
      chemical conclusion. This is, however, not a feasible approach in most studies
      because it is a time-consuming procedure. Therefore, we provide the first
      comprehensive comparison of modern bonding analysis methods to reveal their
      informative value. The element-oxygen bond of neutral Hn XOH model compounds
      (X=Li, Be, B, C, N, O, F, Na, Mg, Al, Si, P, S, Cl) is investigated with a
      selection of different bond analysis tools, which may be assigned into three
      different categories: i) real space bonding indicators (quantum theory of atoms
      in molecules (QTAIM), the electron localizability indicator (ELI-D), and the Raub
      Jansen index), ii) orbital-based descriptors (natural bond orbitals (NBO),
      natural resonance theory (NRT), and valence bond (VB) calculations), and iii)
      energy analysis methods (energy decomposition analysis (EDA) and the Q-analysis).
      Besides gaining a deep insight into the nature of the element-oxygen bond across
      the periodic table, this systematic investigation allows us to get an impression
      on how well these tools complement each other. Ionic, highly polarized, polarized
      covalent, and charge-shift bonds are discerned from each other.

PMID- 29465754
TI  - Core cis-element variation confers subgenome-biased expression of a transcription
      factor that functions in cotton fiber elongation.
AB  - Cotton cultivars have evolved to produce extensive, long, seed-born fibers
      important for the textile industry, but we know little about the molecular
      mechanism underlying spinnable fiber formation. Here, we report how PACLOBUTRAZOL
      RESISTANCE 1 (PRE1) in cotton, which encodes a basic helix-loop-helix (bHLH)
      transcription factor, is a target gene of spinnable fiber evolution. Differential
      expression of homoeologous genes in polyploids is thought to be important to
      plant adaptation and novel phenotypes. PRE1 expression is specific to cotton
      fiber cells, upregulated during their rapid elongation stage and A-homoeologous
      biased in allotetraploid cultivars. Transgenic studies demonstrated that PRE1 is
      a positive regulator of fiber elongation. We determined that the natural
      variation of the canonical TATA-box, a regulatory element commonly found in many
      eukaryotic core promoters, is necessary for subgenome-biased PRE1 expression,
      representing a mechanism underlying the selection of homoeologous genes. Thus,
      variations in the promoter of the cell elongation regulator gene PRE1 have
      contributed to spinnable fiber formation in cotton. Overexpression of GhPRE1 in
      transgenic cotton yields longer fibers with improved quality parameters,
      indicating that this bHLH gene is useful for improving cotton fiber quality.

PMID- 29465757
TI  - Recent Advances in the Cycloisomerizations of Methylenecyclopropanes using Gold
      Catalysis.
AB  - During the past decades, cycloisomerizations of methylenecyclopropanes using gold
      catalysis have attracted much attention from organic chemists. The different
      patterns of gold(I)-catalyzed cycloisomerizations of methylenecyclopropanes have
      been developed, and they can be classified as ring-opening and ring-expansion
      reaction patterns. This synthetic methodology provides a new approach to novel
      cyclic- or polycyclic compounds. The corresponding products have great potential
      for material science, medicinal chemistry and total synthesis. This Concept
      article will mainly focus on the recent advances in the cycloisomerizations of
      methylenecyclopropanes in the past four years.

PMID- 29465758
TI  - An Adverse Effect of Higher Catalyst Loading and Longer Reaction Time on
      Enantioselectivity in an Organocatalytic Multicomponent Reaction.
AB  - An enantioselective organocatalytic multicomponent reaction of aldehydes,
      ketones, and Meldrum's acid has been developed. A cinchona-based primary amine (1
      mol %) catalyses the multicomponent reaction via the formation of the Knoevenagel
      product and a chiral enamine to form enantiopure delta-keto Meldrum's acids in a
      tandem catalytic pathway. An adverse effect of higher catalyst loading and longer
      reaction time on enantioselectivity was studied. This mild protocol provides an
      easy access to enantiopure carboxylic acids, esters and amides and the method is
      scalable on a gram quantity. DFT calculations were carried out on the proposed
      reaction mechanism and they were in close agreement with the experimental
      results.

PMID- 29465759
TI  - Development of a method to preliminarily embed tissue samples using low melting
      temperature fish gelatin before sectioning: A technical note.
AB  - Embedding of tissue samples that maintains a desired orientation is critical for
      preparing sections suitable for diagnosis and study objectives. Methods to
      prepare tissue sections include: (i) paraffin embedding or snap-freezing followed
      by microtome or cryostat sectioning; and (ii) agarose embedding followed by
      cutting on a vibrating microslicer. Although these methods are useful for routine
      laboratory work, preparation of small and fragile tissues such as mouse organs,
      small human biopsy samples, and cultured floating spheres is difficult and
      requires special skills. In particular, tissue specimen orientation can be lost
      during embedding in molds and subsequent sectioning. Here, we developed a method
      using low melting temperature (LM) gelatin either alone or mixed with agarose to
      preliminarily embed collected tissues that are either prefixed or unfixed,
      followed by conventional fixation, paraffin embedding, freezing, and sectioning.
      The advantage of the method is that the LM gelatin and its mixture with agarose
      can be handled at room temperature but quickly hardens at 4 degrees C, which
      allows embedding, trimming, and arranging of small and fragile tissues in a
      desired orientation and are compatible with traditional stainings. Thus, this
      method can have various laboratory applications and can be modified according to
      the needs of each laboratory.

PMID- 29465760
TI  - Angelica sinensis polysaccharide inhibits proliferation, migration, and invasion
      by downregulating microRNA-675 in human neuroblastoma cell line SH-SY5Y.
AB  - Neuroblastoma is the most common tumor diagnosed in children and infants, with
      high recurrence and poor prognosis. Angelica sinensis polysaccharide (AP) whose
      average molecular weight is 72,900 Da possesses various bioactivities. We aimed
      to explore the effects of AP on neuroblastoma SH-SY5Y cells as well as the
      underlying mechanisms. Effects of AP on cell viability, proliferation, apoptosis,
      migration, invasion, and expressions of long noncoding RNA H19 (lncRNA-H19),
      microRNA (miR)-675, and CD44 were assessed. Then, effects of miR-675
      overexpression on AP-treated cells were analyzed. Next, expression of key kinases
      in the PI3K/AKT and JAK/ STAT pathways was detected. The possible target gene of
      miR-675 was finally explored. Cell viability was reduced by 200-500 ug/mL AP.
      Meanwhile, AP repressed cell proliferation, migration, and invasion, but induced
      apoptosis. Expressions of lncRNA-H19 and miR-675 were upregulated in
      neuroblastoma cells, and were downregulated by AP. AP was also identified to
      upregulate CD44. We next found AP affected SH-SY5Y cells through downregulating
      miR-675. Key kinases in the PI3K/AKT and JAK/STAT pathways were downregulated by
      AP stimulation, while these downregulations were abrogated by miR-675
      overexpression. KIF1B isoform beta (KIF1Bbeta) is proved to be a target of miR
      675. In conclusion, AP was first identified to inhibit proliferation, migration,
      and invasion but induce apoptosis. Furthermore, AP might repress tumorigenesis of
      SH-SY5Y cells through miR-675-mediated inactivation of the PI3K/AKT and JAK/STAT
      pathways. Besides, KIF1Bbeta might be a target of miR-675.

PMID- 29465761
TI  - Tumor deposits in salivary gland tumors.
AB  - Tumor deposits (TDs), identified in different types of carcinomas are associated
      with poor prognosis. Salivary gland tumors were evaluated for the first time for
      TDs in this series. Pathological and clinical features of 25 salivary gland
      carcinomas primarily treated surgically including neck dissection were determined
      and all cases were evaluated for TDs in dissection specimens. Seven patients
      (28%) had TDs. There was no difference for TDs when histological type, tumor
      grade, tumor localization, pT, pN stage, surgical margin, lymphovascular,
      perineural invasion, local recurrence, distant metastatic disease and overall
      survival were considered. Disease-free survival rates at 12 and 24 months were
      52.5%, 28.6% and 73.3%, 57.1%, for cases with and without TDs (P = 0.463).
      Overall survival rates at 12 and 24 months for these groups were 85.7% and 57.1
      versus 86.7% and 66.7% respectively (P = 0.916). Mean estimated recurrence-free
      survival time for all cases, TD negative and TD positive cases were: 171.86,
      182.72 and 82.42 months, respectively. Mean estimated overall survival time for
      these groups were 175.80, 186.489 and 89.70 months, respectively. TDs were
      described in salivary gland tumors for the first time in this series and seem to
      be associated with poor prognosis requiring further evaluation in larger series.

PMID- 29465762
TI  - Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer.
AB  - Molecularly targeted therapy has enabled outstanding advances in cancer
      treatment. Whereas various anti-human epidermal growth factor receptor 2 (HER2)
      drugs have been developed, trastuzumab is still the only anti-HER2 drug presently
      available for gastric cancer. In this study, we propose novel treatment options
      for patients with HER2-positive gastric cancer. First, we determined the
      molecular profiles of 12 gastric cancer cell lines, and examined the antitumor
      effect of the pan-HER inhibitors afatinib and neratinib in those cell lines.
      Additionally, we analyzed HER2 alteration in 123 primary gastric cancers resected
      from Japanese patients to clarify possible candidates with the potential to
      respond to these drugs. In the drug sensitivity analysis, both afatinib and
      neratinib produced an antitumor effect in most of the HER2-amplified cell lines.
      However, some cells were not sensitive to the drugs. When the molecular profiles
      of the cells were compared based on the drug sensitivities, we found that cancer
      cells with lower mRNA expression levels of IGFBP7, a tumor suppressor gene that
      inhibits the activation of insulin-like growth factor-1 receptor (IGF-1R), were
      less sensitive to pan-HER inhibitors. A combination therapy consisting of pan-HER
      inhibitors and an IGF-1R inhibitor, picropodophyllin, showed a notable
      synergistic effect. Among 123 clinical samples, we found 19 cases of HER2
      amplification and three cases of oncogenic mutations. In conclusion, afatinib and
      neratinib are promising therapeutic options for the treatment of HER2-amplified
      gastric cancer. In addition to HER2 amplification, IGFBP7 might be a biomarker of
      sensitivity to these drugs, and IGF-1R-targeting therapy can overcome drug
      insensitiveness in HER2-amplified gastric cancer.

PMID- 29465764
TI  - Comparison of two prognostic models in trauma outcome.
AB  - BACKGROUND: The Trauma Audit and Research Network (TARN) in the UK publicly
      reports hospital performance in the management of trauma. The TARN risk
      adjustment model uses a fractional polynomial transformation of the Injury
      Severity Score (ISS) as the measure of anatomical injury severity. The Trauma
      Mortality Prediction Model (TMPM) is an alternative to ISS; this study compared
      the anatomical injury components of the TARN model with the TMPM. METHODS: Data
      from the National Trauma Data Bank for 2011-2015 were analysed. Probability of
      death was estimated for the TARN fractional polynomial transformation of ISS and
      compared with the TMPM. The coefficients for each model were estimated using 80
      per cent of the data set, selected randomly. The remaining 20 per cent of the
      data were used for model validation. TMPM and TARN were compared using
      calibration curves, measures of discrimination (area under receiver operating
      characteristic curves; AUROC), proximity to the true model (Akaike information
      criterion; AIC) and goodness of model fit (Hosmer-Lemeshow test). RESULTS: Some
      438 058 patient records were analysed. TMPM demonstrated preferable AUROC (0.882
      for TMPM versus 0.845 for TARN), AIC (18 204 versus 21 163) and better fit to the
      data (32.4 versus 153.0) compared with TARN. CONCLUSION: TMPM had greater
      discrimination, proximity to the true model and goodness-of-fit than the
      anatomical injury component of TARN. TMPM should be considered for the injury
      severity measure for the comparative assessment of trauma centres.

PMID- 29465763
TI  - The role of bradykinin receptor type 2 in spontaneous extravasation in mice skin:
      implications for non-allergic angio-oedema.
AB  - BACKGROUND AND PURPOSE: Non-allergic angio-oedema is a life-threatening disease
      mediated by activation of bradykinin type 2 receptors (B2 receptors). The aim of
      this study was to investigate whether activation of B2 receptors by endogenous
      bradykinin contributes to physiological extravasation. This may shed new light on
      the assumption that treatment with an angiotensin converting enzyme inhibitor
      (ACEi) results in an alteration in the vascular barrier function predisposing to
      non-allergic angio-oedema. EXPERIMENTAL APPROACH: We generated a new transgenic
      mouse model characterized by endothelium-specific overexpression of the B2
      receptor (B2tg ) and established a non-invasive two-photon laser microscopy
      approach to measure the kinetics of spontaneous extravasation in vivo. The B2tg
      mice showed normal morphology and litter size as compared with their transgene
      negative littermates (B2n ). KEY RESULTS: Overexpression of B2 receptors was
      functional in conductance vessels and resistance vessels as evidenced by B2
      receptor-mediated aortic dilation to bradykinin in presence of non-specific COX
      inhibitor diclofenac and by significant hypotension in B2tg respectively.
      Measurement of dermal extravasation by Miles assay showed that bradykinin induced
      extravasation was significantly increased in B2tg as compared with B2n . However,
      neither endothelial overexpression of B2 receptors nor treatment with the ACEi
      moexipril or B2 antagonist icatibant had any effect on spontaneous extravasation
      measured by two-photon laser microscopy. CONCLUSIONS AND IMPLICATIONS: Activation
      of B2 receptors does not appear to be involved in spontaneous extravasation.
      Therefore, the assumption that treatment with an ACEi results in an alteration in
      the physiological vascular barrier function predisposing to non-allergic angio
      oedema is not supported by our findings.

PMID- 29465765
TI  - The role of general anesthesia on traits of neurodevelopmental disorders in a
      Swedish cohort of twins.
AB  - BACKGROUND: The role of general anesthetics as a risk factor for possible
      neurodevelopmental disorders (NDDs) in humans is unresolved. The investigation of
      the role of anesthetics in the development of postgeneral anesthesia (anesthesia
      onward) NDDs has proven to be complicated, partly because of the inherent
      confounding in clinical cohort studies, and partly by the fact that anesthetics
      are only one part in the complex process of anesthesia-surgery. METHODS:
      Utilizing the Swedish databases Child and Adolescent Twins Study in Sweden
      (CATSS) and National Patient Register (NPR), we investigated twins discordant for
      anesthesia, born between 1997 and 2004 for traits of NDDs. We identified 68 twin
      pairs discordant for anesthesia and explored traits of Attention
      Deficit/Hyperactivity Disorder (ADHD), Learning Disability (LD), and Autism
      Spectrum Disorder (ASD) in them while simultaneously taking congenital
      abnormalities and systemic disorders (CSDs) into account. We analyzed the
      possible effect of anesthesia on neurodevelopmental problems, and we analyzed the
      within-pair differences using conditional linear regression. RESULTS: Twins with
      a recorded episode of anesthesia had higher traits of NDDs than twins without;
      similarly twins with CSDs had higher mean scores on all traits than twins without
      CSDs. The within-pair analyses suggested that exposure to anesthesia was
      associated with higher scores of ADHD (regression coefficient 1.02 and 95%
      confidence intervals: 0.27-1.78) in monozygotic (MZ) twins discordant for
      anesthesia. This effect remained when adjusting for congenital abnormalities.
      DISCUSSION: Our finding that traits of ADHD were slightly associated with
      anesthesia in a genetically sensitive design is in need of replication and
      warrants further investigation. Future studies should aim to elucidate mechanisms
      behind this possible association (e.g. anesthetics doses, age at exposure,
      exposure duration).

PMID- 29465766
TI  - Segmentectomy versus lobectomy in early non-small cell lung cancer of 2 cm or
      less in size: A population-based study.
AB  - BACKGROUND AND OBJECTIVE: Standard surgical management for early stage lung
      cancer is lobectomy with mediastinal lymph node dissection. The feasibility of
      limited resection remains controversial; we retrospectively assessed lung cancer
      specific survival (LCSS) and overall survival (OS) in early stage non-small cell
      lung cancer (NSCLC) to evaluate whether segmentectomy is comparable to standard
      lobectomy. METHODS: Patients with primary NSCLC of 20 mm or less who were
      diagnosed from 2000 to 2014 were extracted from the Surveillance, Epidemiology,
      and End Results (SEER) database. To compare the two surgical interventions, a
      propensity score analysis was performed between lobectomy and segmentectomy.
      RESULTS: Of the 15 358 patients analysed, there were 14 549 lobectomies and 809
      segmentectomies. The 5-year OS was 76% for the lobectomy group and 74.4% for the
      segmentectomy group. There were no significant differences in OS or LCSS among
      patients who underwent lobectomy versus segmentectomy, as demonstrated by the
      propensity-matched hazard ratio (HR) for OS (HR: 1.195, 95% CI: 0.993-1.439) and
      LCSS (HR: 1.124, 95% CI: 0.860-1.469). The inverse propensity-weighted analysis
      also supported these results. Segmentectomy was more likely to be performed in
      elderly patients. In the subset of patients aged >=75 years, the segmentectomy
      group demonstrated comparable OS (HR: 1.17, 95% CI: 0.87-1.58, P = 0.31) and LCSS
      (HR: 0.94, 95% CI: 0.59-1.51, P = 0.81), compared with the lobectomy group.
      CONCLUSION: Equivalent OS and LCSS were demonstrated in patients with primary
      NSCLC of 20 mm or less without lymph node or distant metastasis.

PMID- 29465767
TI  - Molecular characteristics of rhesus macaque interleukin-22: cloning, in vitro
      expression and biological activities.
AB  - Interleukin-22 (IL-22) is a potential therapeutic agent for diseases driven by
      epithelial injury. To characterize the IL-22 expressed by rhesus macaques,
      animals that are irreplaceable for human disease research, rhesus macaque IL-22
      (rhIL-22) was cloned and expressed, and its biological activity and in vivo
      distribution were examined. It was found that the rhIL-22 gene consists of five
      introns and six exons, including a short non-coding exon starting 22 bp
      downstream of a putative TATA box. The amino acid sequence of rhIL-22 showed
      95.5% identity to that of humans, and it shared two conserved disulphide bonds,
      three N-glycosylation sites and all the critical residues for binding to IL-22R1.
      High levels of IL-22 mRNA were observed in the liver, pancreas, lymphoid tissues
      and especially in the outer-body barriers such as the intestinal tract of rhesus
      macaques. Functionally, purified rhIL-22 has a similar but a little earlier
      effect on signal transducer and activator of transcription 3 phosphorylation at
      Tyr705 compared with that of commercial human IL-22. The expression of the
      antibacterial proteins beta-defensin-2, S100A8, S100A9, RegIIIalpha and Muc1 by
      HT-29 cells was largely upregulated after stimulation with rhIL-22. Recombinant
      rhIL-22 could also significantly promote the proliferation of human intestinal
      epithelial cells without affecting cell apoptosis. These data indicate that
      rhesus macaque IL-22 is highly similar to that of humans in both structure and
      function, and tests of therapeutic effects of human IL-22 on human diseases in
      rhesus macaques are warranted.

PMID- 29465768
TI  - Controls on denitrification potential in nitrate-rich waterways and riparian
      zones of an irrigated agricultural setting.
AB  - Denitrification, the microbial conversion of NO3- to N gases, is an important
      process contributing to whether lotic and riparian ecosystems act as sinks for
      excess NO3- from agricultural activities. Though agricultural waterways and
      riparian zones have been a focus of denitrification research for decades, almost
      none of this research has occurred in the irrigated agricultural settings of arid
      and semiarid climates. In this study, we conducted a broad survey of
      denitrification potential in riparian soils and channel sediments from 79
      waterway reaches in the irrigated agricultural landscape of California's Central
      Valley. With this approach, we sought to capture the wide range of variation that
      arose from diverse waterway management and fluctuating flow conditions, and use
      this variation to identify promising management interventions. We explored
      associations of denitrification potentials with surface water NO3- -N, organic
      matter, flow conditions, vegetation cover, near-channel riparian bank slope, and
      channel geomorphic features using generalized linear mixed models. We found
      strong associations of sediment denitrification potentials with reach flow
      conditions, which we hypothesize was the result of variation in microbial
      communities' tolerance to dry-wet cycles. Denitrification potentials in riparian
      soils, in contrast, did not appear affected by flow conditions, but instead were
      associated with organic matter, vegetation cover, and bank slope in the riparian
      zone. These results suggest a strong need for further work on how denitrification
      responds to varying flow conditions and dry-wet cycles in non-perennial lotic
      ecosystems. Our findings also demonstrate that denitrifier communities respond to
      key features of waterway management, which can therefore be leveraged to control
      denitrification through a variety of management actions.

PMID- 29465769
TI  - X-ray-enhanced cancer cell migration requires the linker of nucleoskeleton and
      cytoskeleton complex.
AB  - The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional
      protein complex that is involved in various processes at the nuclear envelope,
      including nuclear migration, mechanotransduction, chromatin tethering and DNA
      damage response. We recently showed that a nuclear envelope protein, Sad1 and
      UNC84 domain protein 1 (SUN1), a component of the LINC complex, has a critical
      function in cell migration. Although ionizing radiation activates cell migration
      and invasion in vivo and in vitro, the underlying molecular mechanism remains
      unknown. Here, we examined the involvement of the LINC complex in radiation
      enhanced cell migration and invasion. A sublethal dose of X-ray radiation
      promoted human breast cancer MDA-MB-231 cell migration and invasion, whereas
      carbon ion beam radiation suppressed these processes in a dose-dependent manner.
      Depletion of SUN1 and SUN2 significantly suppressed X-ray-enhanced cell migration
      and invasion. Moreover, depletion or overexpression of each SUN1 splicing variant
      revealed that SUN1_888 containing 888 amino acids of SUN1 but not SUN1_916 was
      required for X-ray-enhanced migration and invasion. In addition, the results
      suggested that X-ray irradiation affected the expression level of SUN1 splicing
      variants and a SUN protein binding partner, nesprins. Taken together, our
      findings supported that the LINC complex contributed to photon-enhanced cell
      migration and invasion.

PMID- 29465770
TI  - Cookie-cutter shark Isistius spp. predation upon different tuna species from the
      south-western Atlantic Ocean.
AB  - The predation of cookie-cutter sharks Isistius spp. upon the early life stages of
      yellowfin tuna Thunnus albacares, skipjack tuna Katsuwonus pelamis and little
      tunny Euthynnus alletteratus are described. New evidence suggesting a connection
      between commercial fishing and predation by Isistius sp. is presented, with these
      sharks biting tunas hooked in surface waters during daylight. The healing
      patterns of the wounds made by the sharks are described in detail and, although
      such damage is known to negatively influence market price elsewhere, it is not
      the case on the south-east Brazilian coast.

PMID- 29465771
TI  - Site-Specific Studies of Nucleosome Interactions by Solid-State NMR Spectroscopy.
AB  - Chromatin function depends on a dense network of interactions between nucleosomes
      and a wide range of proteins. A detailed description of these protein-nucleosome
      interactions is required to reach a full molecular understanding of chromatin
      function in both genetics and epigenetics. Herein, we show that the structure,
      dynamics, and interactions of nucleosomes can be interrogated in a residue
      specific manner by using state-of-the-art solid-state NMR spectroscopy. Using
      sedimented nucleosomes, high-resolution spectra were obtained for both flexible
      histone tails and the non-mobile histone core. Through co-sedimentation of a
      nucleosome-binding peptide, we demonstrate that protein-binding sites on the
      nucleosome surface can be determined. We believe that this approach holds great
      promise as it is generally applicable, extendable to include the structure and
      dynamics of the bound proteins, and scalable to interactions of proteins with
      higher-order chromatin structures, including isolated and cellular chromatin.

PMID- 29465772
TI  - Superhydrophobic Blood-Repellent Surfaces.
AB  - Superhydrophobic surfaces repel water and, in some cases, other liquids as well.
      The repellency is caused by topographical features at the nano-/microscale and
      low surface energy. Blood is a challenging liquid to repel due to its high
      propensity for activation of intrinsic hemostatic mechanisms, induction of
      coagulation, and platelet activation upon contact with foreign surfaces.
      Imbalanced activation of coagulation drives thrombogenesis or formation of blood
      clots that can occlude the blood flow either on-site or further downstream as
      emboli, exposing tissues to ischemia and infarction. Blood-repellent
      superhydrophobic surfaces aim toward reducing the thrombogenicity of surfaces of
      blood-contacting devices and implants. Several mechanisms that lead to blood
      repellency are proposed, focusing mainly on platelet antiadhesion. Structured
      surfaces can: (i) reduce the effective area exposed to platelets, (ii) reduce the
      adhesion area available to individual platelets, (iii) cause hydrodynamic effects
      that reduce platelet adhesion, and (iv) reduce or alter protein adsorption in a
      way that is not conducive to thrombus formation. These mechanisms benefit from
      the superhydrophobic Cassie state, in which a thin layer of air is trapped
      between the solid surface and the liquid. The connections between water- and
      blood repellency are discussed and several recent examples of blood-repellent
      superhydrophobic surfaces are highlighted.

PMID- 29465773
TI  - Chemical priming of immunity without costs to plant growth.
AB  - beta-Aminobutyric acid (BABA) induces broad-spectrum disease resistance, but also
      represses plant growth, which has limited its exploitation in crop protection.
      BABA perception relies on binding to the aspartyl-tRNA synthetase (AspRS) IBI1,
      which primes the enzyme for secondary defense activity. This study aimed to
      identify structural BABA analogues that induce resistance without stunting plant
      growth. Using site-directed mutagenesis, we demonstrate that the (l)-aspartic
      acid-binding domain of IBI1 is critical for BABA perception. Based on interaction
      models of this domain, we screened a small library of structural BABA analogues
      for growth repression and induced resistance against biotrophic Hyaloperonospora
      arabidopsidis (Hpa). A range of resistance-inducing compounds were identified, of
      which (R)-beta-homoserine (RBH) was the most effective. Surprisingly, RBH acted
      through different pathways than BABA. RBH-induced resistance (RBH-IR) against Hpa
      functioned independently of salicylic acid, partially relied on camalexin, and
      was associated with augmented cell wall defense. RBH-IR against necrotrophic
      Plectosphaerella cucumerina acted via priming of ethylene and jasmonic acid
      defenses. RBH-IR was also effective in tomato against Botrytis cinerea. Metabolic
      profiling revealed that RBH, unlike BABA, does not majorly affect plant
      metabolism. RBH primes distinct defense pathways against biotrophic and
      necrotrophic pathogens without stunting plant growth, signifying strong potential
      for exploitation in crop protection.

PMID- 29465774
TI  - Measuring Resilience to Operational Stress in Canadian Armed Forces Personnel.
AB  - Adaptability to stress is governed by innate resilience, comprised of complex
      neuroendocrine and immune mechanisms alongside inherited or learned behavioral
      traits. Based on their capacity to adapt, some people thrive in stressful
      situations, whereas others experience maladaptation. In our study, we used state
      of-the-art tools to assess the resilience level in individuals, as well as their
      susceptibility to developing military stress-induced behavioral and cognitive
      deficits. To address this complex question, we tested Canadian Armed Forces (CAF)
      personnel in three distinct stress environments (baselines): during predeployment
      training, deployment in Afghanistan, and readjustment upon return to Canada. Our
      comprehensive outcome measures included psychometric tests, saliva biomarkers,
      and computerized cognitive tests that used the Cambridge Neuropsychological
      Automated Test Battery. Participants were categorized based on initial biomarker
      measurements as being at low-, moderate-, or high stress-maladaptation risk.
      Biomarkers showed significant changes (ds = 0.56 to 2.44) between baselines,
      calculated as "delta" changes. Participants at low stress-maladaptation risk
      demonstrated minimal changes, whereas those at high stress-maladaptation risk
      showed significant biomarker variations. The psychometric patterns and cognitive
      functions were likewise affected across baselines, suggesting that the panel of
      saliva stress biomarkers could be a useful tool for determining the risk of
      stress maladaptation that can cause psychological and cognitive decline.

PMID- 29465775
TI  - Identification of the correlation between illness perception and anxiety level in
      cancer patients.
AB  - PURPOSE: To investigate the relationship between the perception of the disease
      and level of anxiety in patients with cancer. DESIGN AND METHODS: A correlation
      and descriptive study from a convenience sample of 318 oncological patients aged
      18 years and older was done. Subjects were measured with a Patient's Information
      Form, the Revised Illness Perception Questionnare, and the Strait-Trait Anxiety
      Inventory. FINDINGS: When evaluated together with most of its subscales, illness
      perception was found to affect anxiety. PRACTICE IMPLICATIONS: Nurses should
      evaluate the anxiety levels of the cancer patients in every stage and should
      educate the patients and their relatives on coping with anxiety. Appropriate
      treatment and care depending on the illness perception of the cancer patients
      should be planned by nurses.

PMID- 29465776
TI  - Fair chances and hard work? Families making sense of inequality and opportunity
      in 21st-century Britain.
AB  - In British social mobility discourse, the rhetoric of fair access can obscure
      wider issues of social justice. While socio-economic inequalities continue to
      shape young people's lives, sociological work on class dis-identification
      suggests social class is less obviously meaningful as a source of individual and
      collective identity. This paper considers subjective understandings of the post
      16 education and employment landscape in this context, drawing on qualitative
      research exploring the aspirations of young men and women as they completed
      compulsory education in north-west England, and the hopes their parents had for
      their future. It shows how unequal access to resources shaped the older
      generation's expectations for their children, although this was rarely
      articulated using the explicit language of class. Their children recognized they
      faced a difficult job market but embraced the idea that success was possible
      through hard work. Both generations drew moral boundaries and made judgments
      based on implicit classed discourses about undeserving others, while at the same
      time disavowing class identities. There was a more explicit recognition of gender
      inequality among the parents framed with reference to hopes for greater freedom
      for their daughters. Opportunities and inequalities were thus understood in
      complex and sometimes contradictory ways.

PMID- 29465777
TI  - Expression of MAGE-A and NY-ESO-1 cancer/testis antigens is enriched in triple
      negative invasive breast cancers.
AB  - AIMS: A better understanding of the expression of cancer/testis antigens (CTAs)
      in breast cancer might enable the identification of new immunotherapy options,
      especially for triple-negative (TN) tumours, which lack expression of the
      conventional therapeutic targets oestrogen receptor, progesterone receptor, and
      human epidermal growth factor receptor 2. The aim of this study was to quantify
      the expression of MAGE-A and NY-ESO-1 CTAs in breast cancer, and relate this to
      known clinicopathological parameters. METHODS AND RESULTS: We surveyed MAGE-A and
      NY-ESO-1 expression in an unselected cohort of 367 breast tumours (of which 65
      were TN), with accompanying clinical follow-up data, by using immunohistochemical
      analysis of tissue microarrays. Relevant to their potential as vaccine targets in
      breast cancer, MAGE-A was expressed in 13% of cases, and NY-ESO-1 in 3.8%, with
      the majority of tumours showing fairly homogeneous staining within individual
      tissue cores (~85% of cases with staining in >75% of tumour cells). Most NY-ESO-1
      positive cases also expressed MAGE-A (P = 2.06 * 10-9 ), and both were strongly
      associated with the TN phenotype (P < 0.0001), with the most proliferative and
      poorly differentiated cases, in paticular, showing genomic instability. This was
      characterised by coexpression of c-Kit and TTK, and overexpression of p53.
      CONCLUSIONS: MAGE-A and NY-ESO-1 are frequently expressed in TN breast cancer
      (~47% and 17% of TN cases, respectively), suggesting that targeting them could be
      feasible in this patient group. Expression is reasonably homogeneous in positive
      cases, suggesting that immunohistochemical analysis of tissue biopsies would be a
      reliable companion biomarker.

PMID- 29465778
TI  - The O-GlcNAc transferase OGT interacts with and post-translationally modifies the
      transcription factor HOXA1.
AB  - HOXA1 belongs to the HOX family of transcription factors which are key regulators
      of animal development. Little is known about the molecular pathways controlling
      HOXA1. Recent data from our group revealed distinct partner proteins interacting
      with HOXA1. Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc)
      transferase modifying a variety of proteins involved in different cellular
      processes including transcription. Here, we confirm OGT as a HOXA1 interactor, we
      characterise which domains of HOXA1 and OGT are required for the interaction, and
      we provide evidence that OGT post-translationally modifies HOXA1. Mass
      spectrometry experiments indeed reveal that HOXA1 can be phosphorylated on the
      AGGTVGSPQYIHHSY peptide and that upon OGT expression, the phosphate adduct is
      replaced by an O-GlcNAc group.

PMID- 29465779
TI  - Atlantic sturgeon Acipenser oxyrinchus surfacing behaviour.
AB  - Atlantic sturgeon Acipenser oxyrinchus surfacing behaviour was investigated in
      Minas Basin (45 degrees  20' N; 64 degrees  00' W) and the Bay of Fundy with pop
      up satellite archival tags (MiniPAT) measuring physical variables (pressure,
      temperature, light). Of six tags deployed during June and July, five provided pop
      up locations and two were recovered after c. 4 months. Analysis of recovered
      archival data revealed that the frequency of surfacing events was highest (78.9%)
      when A. oxyrinchus were in Minas Basin at depths <10 m. Surfacing frequency
      decreased substantially when fish migrated into greater depths of the Bay of
      Fundy (>40 m). The tidal cycle in Minas Basin had a significant relationship to
      surfacing frequency, with the most surfacing events (49.5%) occurring on the
      flood tide, from mid- to high-tide. Surfacing events ranged from 0-12 a day and
      the maximum number occurred between 2300 and 0300 hours. Maximum surfacing ascent
      speeds ranged from 0.50 to 4.17 m s-1 and maximum descent speeds ranged from 0.17
      to 3.17 m s-1 . Buoyancy control, by gulping air to inflate the gas bladder, is
      proposed as the main reason for surfacing behaviour in A. oxyrinchus.

PMID- 29465780
TI  - Inferring species interactions through joint mark-recapture analysis.
AB  - Introduced species are frequently implicated in declines of native species. In
      many cases, however, evidence linking introduced species to native declines is
      weak. Failure to make strong inferences regarding the role of introduced species
      can hamper attempts to predict population viability and delay effective
      management responses. For many species, mark-recapture analysis is the more
      rigorous form of demographic analysis. However, to our knowledge, there are no
      mark-recapture models that allow for joint modeling of interacting species. Here,
      we introduce a two-species mark-recapture population model in which the vital
      rates (and capture probabilities) of one species are allowed to vary in response
      to the abundance of the other species. We use a simulation study to explore bias
      and choose an approach to model selection. We then use the model to investigate
      species interactions between endangered humpback chub (Gila cypha) and introduced
      rainbow trout (Oncorhynchus mykiss) in the Colorado River between 2009 and 2016.
      In particular, we test hypotheses about how two environmental factors (turbidity
      and temperature), intraspecific density dependence, and rainbow trout abundance
      are related to survival, growth, and capture of juvenile humpback chub. We also
      project the long-term effects of different rainbow trout abundances on adult
      humpback chub abundances. Our simulation study suggests this approach has minimal
      bias under potentially challenging circumstances (i.e., low capture
      probabilities) that characterized our application and that model selection using
      indicator variables could reliably identify the true generating model even when
      process error was high. When the model was applied to rainbow trout and humpback
      chub, we identified negative relationships between rainbow trout abundance and
      the survival, growth, and capture probability of juvenile humpback chub. Effects
      on interspecific interactions on survival and capture probability were strongly
      supported, whereas support for the growth effect was weaker. Environmental
      factors were also identified to be important and in many cases stronger than
      interspecific interactions, and there was still substantial unexplained variation
      in growth and survival rates. The general approach presented here for combining
      mark-recapture data for two species is applicable in many other systems and could
      be modified to model abundance of the invader via other modeling approaches.

PMID- 29465781
TI  - Lichen planus pemphigoides.

PMID- 29465782
TI  - Dielectric properties for non-invasive detection of normal, benign, and malignant
      breast tissues using microwave theories.
AB  - BACKGROUND: Despite the high incidence of breast cancer worldwide, methods for
      early non-invasive diagnosis and sensitive and specific prognostic evaluation
      remain difficult. In this study, we investigated microwave parameters as a
      potential non-invasive approach to detect breast cancer. METHODS: Samples of
      freshly excised breast tissues (n = 509) from 98 patients were identified as
      normal, benign tumor, or malignant cancer via histology. Further samples were
      prepared and the microwave effective dielectric permittivity and effective
      conductivity were measured every 0.0375 GHz from 0.5 GHz to 8 GHz. These
      parameters were compared among the breast tissue types. RESULTS: The effective
      relative permittivity and effective conductivity at each frequency was
      significantly higher in breast cancer tissues compared with benign tumors, which
      in turn was significantly higher than in normal breast tissue. The standard
      deviation of each parameter was narrowest at ~2.5 GHz in both normal and
      malignant breast tissues. CONCLUSIONS: The effective dielectric permittivity and
      effective conductivity, measured via microwave technology, could differentiate
      breast cancer from normal and benign tumor tissues.

PMID- 29465783
TI  - New Water-Soluble Cluster Compound {Zn(en)3 }3 [V15 Sb6 O42 (H2 O)]?
      (Ethylenediamine)3 ?10 H2 O as a Synthon for the Generation of Two New Antimonato
      Polyoxovanadates.
AB  - A new antimonato polyoxovanadate {Zn(en)3 }3 [V15 Sb6 O42 (H2 O)]?3 en?10 H2 O
      (en=ethylenediamine) synthesized under hydrothermal conditions exhibits
      remarkable solubility in water. Electrospray ionization mass spectrometry (ESI
      MS) investigations on an aqueous solution demonstrate that the cluster core
      remains fully intact for 72 h. At longer times, slow transformation into a {V14
      Sb8 O42 } cluster is observed. The conversion reaches 50 % after 14 days and is
      complete after approximately 20 days. The rate of this {V15 Sb6 }->{V14 Sb8 }
      cluster transformation is significantly increased in the presence of ammonium
      acetate. Applying the new compound as a synthon in the presence of 1,10
      phenanthroline (phen) led to crystallization of {Zn(phen)3 }2 [Zn(en)2 V15 Sb6
      O42 (H2 O)]?23 H2 O after a short reaction time, whereas addition of Sb2 O3 led
      to fast crystallization of {(Zn(en)2 (H2 O)2 )(Zn(en)2 )}[Zn(en)2 V15 Sb6 O42 (H2
      O)] ?8.5 H2 O. In the crystal structure of {Zn(en)3 }3 [V15 Sb6 O42 (H2 O)]?3
      en?10 H2 O, the en molecules are seen to be attached to the cluster anion through
      Sb-N bonds. In the structures of the two new compounds obtained, the [V15 Sb6 O42
      (H2 O)]6- anions are expanded by Zn2+ -centered complexes through Zn-O-V bond
      formation.

PMID- 29465784
TI  - An unexpected result following sentinel lymph node biopsy for desmoplastic
      cutaneous squamous cell carcinoma.

PMID- 29465785
TI  - The Hydrophobic Effect Applied to Organic Synthesis: Recent Synthetic Chemistry
      "in Water".
AB  - Recent developments over the past few years in aqueous micellar catalysis are
      discussed. Applications to problems in synthesis are highlighted, enabled by the
      use of surfactants that self-aggregate in water into micelles as nanoreactors.
      These include amphiphiles that have been available for some time, as well as
      those that have been newly designed. Reactions catalyzed by transition metals,
      including Pd, Cu, Rh, and Au, are of particular focus.

PMID- 29465786
TI  - Subpopulations of vomeronasal sensory neurons with coordinated coexpression of
      type 2 vomeronasal receptor genes are differentially dependent on Vmn2r1.
AB  - The mouse vomeronasal organ is specialized in the detection of pheromones.
      Vomeronasal sensory neurons (VSNs) express chemosensory receptors of two large
      gene repertoires, V1R and V2R, which encode G-protein-coupled receptors.
      Phylogenetically, four families of V2R genes can be discerned as follows: A, B,
      C, and D. VSNs located in the basal layer of the vomeronasal epithelium
      coordinately coexpress V2R genes from two families: Approximately half of basal
      VSNs coexpress Vmn2r1 of family C with a single V2R gene of family A8-10, B, or D
      ('C1 type of V2Rs'), and the other half coexpress Vmn2r2 through Vmn2r7 of family
      C with a single V2R gene of family A1-6 ('C2 type V2Rs'). The regulatory
      mechanisms of the coordinated coexpression of V2Rs from two families remain
      poorly understood. Here, we have generated two mouse strains carrying a knockout
      mutation in Vmn2r1 by gene targeting in embryonic stem cells. These mutations
      cause a differential decrease in the numbers of VSNs expressing a given C1 type
      of V2R. There is no compensatory expression of Vmn2r2 through Vmn2r7. VSN axons
      coalesce into glomeruli in the appropriate region of the accessory olfactory bulb
      in the absence of Vmn2r1. Gene expression profiling by NanoString reveals a
      differential and graded decrease in the expression levels across C1 type of V2Rs.
      There is no change in the expression levels of C2 type of V2Rs, with two
      exceptions that we reclassified as C1 type. Thus, there appears to be a fixed
      probability of gene choice for a given C2 type of V2R.

PMID- 29465787
TI  - Nonmotor symptoms evolution during 24 months of bilateral subthalamic stimulation
      in Parkinson's disease.
AB  - BACKGROUND: The objective of this study was to investigate 24-month of effects of
      bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on nonmotor
      symptoms in Parkinson's disease (PD). METHODS: In this prospective,
      observational, multicenter, international study including 67 PD patients
      undergoing bilateral STN-DBS, we examined the Non-motor Symptom Scale, Non-Motor
      Symptoms Questionnaire, Parkinson's Disease Questionnaire-8, Scales for Outcomes
      in Parkinson's Disease-motor examination, -activities of daily living, and 
      complications, and levodopa-equivalent daily dose preoperatively and at 5 and 24
      month of follow-up. After checking distribution normality, longitudinal outcome
      changes were investigated with Friedman tests or repeated-measures analysis of
      variance and Bonferroni correction for multiple comparisons using multiple tests.
      Post hoc, Wilcoxon signed rank t tests were computed to compare visits. The
      strength of clinical responses was analyzed using effect size. Explorative
      Spearman correlations of change scores from baseline to 24-month follow-up were
      calculated for all outcomes. RESULTS: The Non-motor Symptom Scale and all other
      outcome parameters significantly improved from baseline to the 5-month follow-up.
      From 5 to 24-month, partial decrements in these gains were found. Nonetheless,
      comparing baseline with 24-month follow-up, significant improvements were
      observed for the Non-motor Symptom Scale (small effect), Scales for Outcomes in
      PD-motor examination showed a moderate effect, and Scales for Outcomes in
      Parkinson's Disease-complications and levodopa-equivalent daily dose showed large
      effects. Non-motor Symptom Scale change scores from baseline to 24-month follow
      up correlated significantly with Parkinson's Disease Questionnaire-8, Scales for
      Outcomes in Parkinson's Disease-activities of daily living, and -motor
      complications change scores. CONCLUSIONS: This study provides evidence of
      beneficial effects of bilateral STN-DBS on nonmotor symptoms at 24-month follow
      up. The extent of nonmotor symptom improvement was directly proportionate to
      improvements in quality of life, activities of daily living, and motor
      complications. This study underlines the importance of nonmotor symptoms for
      holistic assessments of DBS outcomes. (c) 2018 International Parkinson and
      Movement Disorder Society.

PMID- 29465789
TI  - A real-world experience with augmentation enterocystoplasty-High patient
      satisfaction with high complication rates.
AB  - AIMS: To investigate the real treatment outcomes after augmentation
      enterocystoplasty (AE) of patients with refractory neurogenic lower urinary tract
      dysfunction. METHODS: Retrospective follow-up in a single center. The
      videourodynamic data, renal function, incontinence grade, voiding pattern and
      management, clinical outcome, and complications were evaluated. RESULTS: Seventy
      nine patients (62 men and 17 women) were included. The mean age at operation was
      39.4 +/- 11.6 years and the mean follow-up period was 128.4 +/- 85.2 months. At
      follow-up, 5 (6.7%) patients had spontaneous voiding, 60 (80%) had to perform
      clean intermittent catheterization, and 10 (13.3%) chose to keep the indwelling
      catheter. The catheter-dependent rate was 93.3% and complete catheter-dependent
      rate was 76%. Renal function of the patients did not appear to be significantly
      different after AE. Three patients developed end-stage renal disease. The
      incontinence grade showed significant improvement (P = 0.000). Among all the
      patients, 41.8% experienced recurrent urinary tract infections requiring medical
      treatment and 21.5% suffered from chronic diarrhea. Overall, 45.6% of the
      patients experienced complications requiring surgical interventions, most of
      which were stones. Life-threatening complications like bowel obstruction and
      bladder cancer were also noted. Three patients even expired within one year
      postoperatively. The majority (86.8%) of patients reported moderate to excellent
      satisfaction with the outcome of AE. CONCLUSIONS: AE is a procedure with long
      term durability and high rates of patient satisfaction. However, several
      bothersome complications affecting life quality may occur. Both patients and
      doctors thus need to consider possible outcomes carefully before the operation.

PMID- 29465788
TI  - Biomarker potential of ST6GALNAC3 and ZNF660 promoter hypermethylation in
      prostate cancer tissue and liquid biopsies.
AB  - Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal,
      leading to overdiagnosis and overtreatment. Aberrant promoter hypermethylation of
      specific genes has been suggested as novel candidate biomarkers for PC that may
      improve diagnosis and prognosis. We here analyzed ST6GALNAC3 and ZNF660 promoter
      methylation in prostate tissues, and ST6GALNAC3, ZNF660, CCDC181, and HAPLN3
      promoter methylation in liquid biopsies. First, using four independent patient
      sample sets, including a total of 110 nonmalignant (NM) and 705 PC tissue
      samples, analyzed by methylation-specific qPCR or methylation array, we found
      that hypermethylation of ST6GALNAC3 and ZNF660 was highly cancer-specific with
      areas under the curve (AUC) of receiver operating characteristic (ROC) curve
      analysis of 0.917-0.995 and 0.846-0.903, respectively. Furthermore, ZNF660
      hypermethylation was significantly associated with biochemical recurrence in two
      radical prostatectomy (RP) cohorts of 158 and 392 patients and remained
      significant also in the subsets of patients with Gleason score <=7 (univariate
      Cox regression and log-rank tests, P < 0.05), suggesting that ZNF660 methylation
      analysis can potentially help to stratify low-/intermediate-grade PCs into
      indolent vs. more aggressive subtypes. Notably, ZNF660 hypermethylation was also
      significantly associated with poor overall and PC-specific survival in the RP
      cohort (n = 158) with long clinical follow-up available. Moreover, as proof of
      principle, we successfully detected highly PC-specific hypermethylated
      circulating tumor DNA (ctDNA) for ST6GALNAC3, ZNF660, HAPLN3, and CCDC181 in
      liquid biopsies (serum) from 27 patients with PC vs. 10 patients with BPH, using
      droplet digital methylation-specific PCR analysis. Finally, we generated a three
      gene (ST6GALNAC3/CCDC181/HAPLN3) ctDNA hypermethylation model, which detected PC
      with 100% specificity and 67% sensitivity. In conclusion, we here for the first
      time demonstrate diagnostic biomarker potential of ST6GALNAC3 and ZNF660
      methylation, as well as prognostic biomarker potential of ZNF660. Furthermore, we
      show that hypermethylation of four genes can be detected in ctDNA in liquid
      biopsies (serum) from patients with PC.

PMID- 29465790
TI  - Forkhead box C2 promotes the invasion ability of human trophoblast cells through
      Hedgehog (Hh) signaling pathway.
AB  - Embryonic development depends on the normal invasion of trophoblast cells.
      Forkhead box C2 (FOXC2) is a member of Forkhead box family, which is involved in
      the tumor cells invasion. The aim of this study was to explore the roles of FOXC2
      on the invasion of human trophoblast cells, and further study its molecular
      mechanism. The mRNA and protein levels of FOXC2 in human normal trophoblast and
      choriocarcinoma cell lines were analyzed by quantitative real-time PCR (qRT-PCR)
      and Western blot assays, respectively. Methylthiazolyldiphenyl-tetrazo lium
      bromide (MTT) and transwell assays were separately performed to detect the
      adhesion and invasion of normal trophoblast cells treated with exogenous FOXC2
      and FOXC2 siRNA. QRT-PCR and Western blot assays were used to test levels of the
      epithelial-mesenchymal transition (EMT)-related and Hedgehog (Hh) signaling
      pathway-related factors, respectively. Herein, our results found that the
      expression levels of FOXC2 in normal trophoblast cells were lower than
      choriocarcinoma cells. FOXC2 over-expression remarkably strengthened the adhesion
      and invasion abilities of normal trophoblast cells. Moreover, over-expression of
      FOXC2 significantly promoted the expression of human leukocyte antigen-G (HLA-G),
      matrix metalloproteinase-2 (MMP-2), Vimentin, sonic hedgehog (Shh), Glioma
      associated oncogene homolog 1 (Gli1), and Snail, and inhibited E-cadherin
      expression. However, it showed the opposite tendency in FOXC2 siRNA group. In
      addition, there was no significant change in the expression of MMP9 among
      different groups. Above results illustrated that FOXC2 could promote the invasion
      ability of normal trophoblast cells by EMT-mediated Hh pathway.

PMID- 29465791
TI  - Identification and functional analysis of a novel chorion protein essential for
      egg maturation in the brown planthopper.
AB  - In insect eggs, the chorion has the essential function of protecting the embryo
      from external agents during development while allowing gas exchange for
      respiration. In this study, we found a novel gene, Nilaparvata lugens chorion
      protein (NlChP), that is involved in chorion formation in the brown planthopper,
      Nilaparvata lugens. NlChP was highly expressed in the follicular cells of female
      adult brown planthoppers. Knockdown of NlChP resulted in oocyte malformation and
      the inability to perform oviposition, and electron microscopy showed that the
      malformed oocytes had thin and rough endochorion layers compared to the control
      group. Liquid chromatography with tandem mass spectrometry analysis of the
      eggshell components revealed four unique peptides that were matched to NlChP. Our
      results demonstrate that NlChP is a novel chorion protein essential for egg
      maturation in N. lugens, a hemipteran insect with telotrophic meroistic ovaries.
      NlChP may be a potential target in RNA interference-based insect pest management.

PMID- 29465792
TI  - Uterine adenomatoid tumor containing epithelioid oxyphilic cells showing
      prominent down-expression of HBME1 and increased Ki-67 labeling index.

PMID- 29465793
TI  - Modulation of task-related cortical connectivity in the acute and subacute phase
      after stroke.
AB  - The functional relevance of cortical reorganization post-stroke is still not well
      understood. In this study, we investigated task-specific modulation of cortical
      connectivity between neural oscillations in key motor regions during the early
      phase after stroke. EEG and EMG recordings were examined from 15 patients and 18
      controls during a precision grip task using the affected hand. Each patient
      attended two sessions in the acute and subacute phase (median of 3 and 34 days)
      post-stroke. Dynamic causal modelling (DCM) for induced responses was used to
      investigate task-specific modulations of oscillatory couplings in a bilateral
      network comprising supplementary motor area (SMA), dorsal premotor cortex (PMd)
      and primary motor cortex (M1). Fourteen models were constructed for each subject,
      and the input induced by the experimental manipulation (task) was set to inferior
      parietal lobule (IPL). Bayesian model selection favoured a fully connected model.
      A reduced coupling from SMA and intact M1 in the gamma-band (31-48 Hz) to
      lesioned M1 in the beta-band (15-30 Hz) was observed in patients in the acute
      phase compared to controls. Behavioural performance improved significantly in the
      subacute phase, while an increased positive coupling from intact PMd to lesioned
      M1 and a less negative modulation from lesioned M1 to intact M1 were observed for
      patients compared to controls both from the gamma-band to the beta-band. We infer
      that the observed differences in cross-frequency cortical interactions are
      important for functional recovery.

PMID- 29465794
TI  - Liver involvement in dengue viral infections.
AB  - Dengue fever is the commonest viral haemorrhagic fever worldwide and is a leading
      cause of morbidity and mortality in the tropics. Dengue viral infections are
      frequently associated with varying degrees of liver injury. Liver injury is more
      severe in dengue haemorrhagic fever or severe dengue. We review the current
      knowledge on liver involvement following dengue viral infections and explore the
      links between clinical manifestations, pathogenesis, and their impact on
      management.

PMID- 29465795
TI  - Enhanced Li Storage Stability Induced by Locating Sn in Metal-Organic Frameworks.
AB  - By locating elemental Sn in an open anionic framework, the particle cracking
      arising from huge volume expansion of Sn-based anode materials during
      lithiation/delithiation is alleviated, and the cycling stability is greatly
      improved. The Sn-based metal-organic framework anode material shows superior
      cyclic stability, with a capacity retention >92 % (after 200 cycles) and high
      lithium storage capacity (610 mAh g-1 ).

PMID- 29465796
TI  - Conserved residues are critical for Haloferax volcanii archaeosortase catalytic
      activity: Implications for convergent evolution of the catalytic mechanisms of
      non-homologous sortases from archaea and bacteria.
AB  - Proper protein anchoring is key to the biogenesis of prokaryotic cell surfaces,
      dynamic, resilient structures that play crucial roles in various cell processes.
      A novel surface protein anchoring mechanism in Haloferax volcanii depends upon
      the peptidase archaeosortase A (ArtA) processing C-termini of substrates
      containing C-terminal tripartite structures and anchoring mature substrates to
      the cell membrane via intercalation of lipid-modified C-terminal amino acid
      residues. While this membrane protein lacks clear homology to soluble sortase
      transpeptidases of Gram-positive bacteria, which also process C-termini of
      substrates whose C-terminal tripartite structures resemble those of ArtA
      substrates, archaeosortases do contain conserved cysteine, arginine and
      arginine/histidine/asparagine residues, reminiscent of His-Cys-Arg residues of
      sortase catalytic sites. The study presented here shows that ArtAWT -GFP
      expressed in trans complements DeltaartA growth and motility phenotypes, while
      alanine substitution mutants, Cys173 (C173A), Arg214 (R214A) or Arg253 (R253A),
      and the serine substitution mutant for Cys173 (C173S), fail to complement these
      phenotypes. Consistent with sortase active site replacement mutants, ArtAC173A 
      GFP, ArtAC173S -GFP and ArtAR214A -GFP cannot process substrates, while
      replacement of the third residue, ArtAR253A -GFP retains some processing
      activity. These findings support the view that similarities between certain
      aspects of the structures and functions of the sortases and archaeosortases are
      the result of convergent evolution.

PMID- 29465797
TI  - Organoactinide-Catalyzed Monohydroboration of Carbodiimides.
AB  - The organoactinide-catalyzed monohydroboration of carbodiimides is reported
      herein. The catalytic reactions proceed under very mild conditions in a highly
      atom-efficient and highly selective fashion to afford the corresponding
      monohydroborated N-borylformamidine products in high yields. A plausible
      mechanism is proposed based on stoichiometric and kinetic studies.

PMID- 29465798
TI  - Sexual conflict and ecology: Species composition and male density interact to
      reduce male mating harassment and increase female survival.
AB  - Sexual conflict is a pervasive evolutionary force that can reduce female fitness.
      Experimental evolution studies in the laboratory might overestimate the
      importance of sexual conflict because the ecological conditions in such settings
      typically include only a single species. Here, we experimentally manipulated
      conspecific male density (high or low) and species composition (sympatric or
      allopatric) to investigate how ecological conditions affect female survival in a
      sexually dimorphic insect, the banded demoiselle (Calopteryx splendens). Female
      survival was strongly influenced by an interaction between male density and
      species composition. Specifically, at low conspecific male density, female
      survival increased in the presence of heterospecific males (C. virgo). Behavioral
      mating experiments showed that interspecific interference competition reduced
      conspecific male mating success with large females. These findings suggest that
      reproductive interference competition between con- and heterospecific males might
      indirectly facilitate female survival by reducing mating harassment from
      conspecific males. Hence, interspecific competitors can show contrasting effects
      on the two sexes thereby influencing sexual conflict dynamics. Our results call
      for incorporation of more ecological realism in sexual conflict research,
      particularly how local community context and reproductive interference
      competition between heterospecific males can affect female fitness.

PMID- 29465799
TI  - Imaging of Al/Fe ratios in synthetic Al-goethite revealed by nanoscale secondary
      ion mass spectrometry.
AB  - RATIONALE: Aluminium (Al)-substituted goethite is ubiquitous in soils and
      sediments. The extent of Al-substitution affects the physicochemical properties
      of the mineral and influences its macroscale properties. Bulk analysis only
      provides total Al/Fe ratios without providing information with respect to the Al
      substitution of single minerals. Here, we demonstrate that nanoscale secondary
      ion mass spectrometry (NanoSIMS) enables the precise determination of Al-content
      in single minerals, while simultaneously visualising the variation of the Al/Fe
      ratio. METHODS: Al-substituted goethite samples were synthesized with increasing
      Al concentrations of 0.1, 3, and 7 % and analysed by NanoSIMS in combination with
      established bulk spectroscopic methods (XRD, FTIR, Mossbauer spectroscopy). The
      high spatial resolution (50-150 nm) of NanoSIMS is accompanied by a high number
      of single-point measurements. We statistically evaluated the Al/Fe ratios derived
      from NanoSIMS, while maintaining the spatial information and reassigning it to
      its original localization. RESULTS: XRD analyses confirmed increasing
      concentration of incorporated Al within the goethite structure. Mossbauer
      spectroscopy revealed 11 % of the goethite samples generated at high Al
      concentrations consisted of hematite. The NanoSIMS data show that the Al/Fe
      ratios are in agreement with bulk data derived from total digestion and
      demonstrated small spatial variability between single-point measurements. More
      advantageously, statistical analysis and reassignment of single-point
      measurements allowed us to identify distinct spots with significantly higher or
      lower Al/Fe ratios. CONCLUSIONS: NanoSIMS measurements confirmed the capacity to
      produce images, which indicated the uniform increase in Al-concentrations in
      goethite. Using a combination of statistical analysis with information from
      complementary spectroscopic techniques (XRD, FTIR and Mossbauer spectroscopy) we
      were further able to reveal spots with lower Al/Fe ratios as hematite.

PMID- 29465800
TI  - The cycling gonad: retinoic-acid synthesis and degradation patterns during adult
      zebrafish Danio rerio oogenesis.
AB  - The expression pattern of genes coding for enzymes of the retinoic acid (RA)
      synthetic and degradation pathways was characterized in adult female zebrafish
      Danio rerio. Females were conditioned until maturation and post-spawn expression
      dynamics were determined. A striking upregulation of cyp26b1, but not cyp26a1,
      was observed following egg deposition, decreasing to initial levels during
      recovery. A similar, yet lower, fluctuation was observed for aldh1a2 and rdh10a,
      the enzymes participating in the two-step RA biosynthesis cascade. The present
      work highlights the dynamics of the adult D. rerio oogenesis and uncovers novel,
      yet elusive, metabolic contributors. Possible compartmentalized roles for the
      different gene paralogue isoforms are discussed.

PMID- 29465801
TI  - Near-Infrared Light-Controlled Gene Expression and Protein Targeting in Neurons
      and Non-neuronal Cells.
AB  - Near-infrared (NIR) light-inducible binding of bacterial phytochrome BphP1 to its
      engineered partner, QPAS1, is used for optical protein regulation in mammalian
      cells. However, there are no data on the application of the BphP1-QPAS1 pair in
      cells derived from various mammalian tissues. Here, we tested the functionality
      of two BphP1-QPAS1-based optogenetic tools-an NIR- and blue-light-sensing system
      for control of protein localization (iRIS) and an NIR light-sensing system for
      transcription activation (TA)-in several cell types, including cortical neurons.
      We found that the performance of these optogenetic tools often relied on
      physiological properties of a specific cell type, such as nuclear transport,
      which could limit the applicability of the blue-light-sensitive component of
      iRIS. In contrast, the NIR-light-sensing component of iRIS performed well in all
      tested cell types. The TA system showed the best performance in cervical cancer
      (HeLa), bone cancer (U-2 OS), and human embryonic kidney (HEK-293) cells. The
      small size of the QPAS1 component allowed the design of adeno-associated virus
      (AAV) particles, which were applied to deliver the TA system to neurons.

PMID- 29465802
TI  - Cholesterol accumulation by suppression of SMT1 leads to dwarfism and improved
      drought tolerance in herbaceous plants.
AB  - Dwarfism and drought tolerance are 2 valuable traits in breeding of many crops.
      In this study, we report the novel physiological roles of cholesterol in
      regulation of plant growth and drought tolerance. Compared with the wild type,
      sterol-C24-methyltransferase 1 (SMT1) gene transcript was greatly reduced in a
      bermudagrass mutant with dwarfism and enhanced drought tolerance, accompanied
      with cholesterol accumulation, elevated transcript levels of a small group of
      genes including SAMDC, and increased concentrations of putrescine (Put),
      spermidine (Spd), and spermine (Spm). Knock-down of OsSMT1 expression by RNA
      interference resulted in similar phenotypic changes in transgenic rice. Moreover,
      exogenously applied cholesterol also led to elevated transcripts of a similar set
      of genes, higher levels of Put, Spd, and Spm, improved drought tolerance, and
      reduced plant height in both bermudagrass and rice. We revealed that it is Spm,
      but not Spd, that is responsible for the height reduction in bermudagrass and
      rice. In conclusion, we suggest that cholesterol induces expression of SAMDC and
      leads to dwarfism and elevated drought tolerance in plants as a result of the
      promoted Spd and Spm synthesis.

PMID- 29465803
TI  - Olaparib is effective in combination with, and as maintenance therapy after,
      first-line endocrine therapy in prostate cancer cells.
AB  - A number of prostate cancer (PCa)-specific genomic aberrations (denominated
      BRCAness genes) have been discovered implicating sensitivity to PARP inhibition
      within the concept of synthetic lethality. Recent clinical studies show favorable
      results for the PARP inhibitor olaparib used as single agent for treatment of
      metastatic castration-resistant PCa. Using 2D and 3D cell culture models
      mimicking the different treatment and progression stages of PCa, we evaluated a
      potential use for olaparib in combination with first-line endocrine treatments,
      androgen deprivation, and complete androgen blockade, and as a maintenance
      therapy following on from endocrine therapy. We demonstrate that the LNCaP cell
      line, possessing multiple aberrations in BRCAness genes, is sensitive to
      olaparib. Additive effects of olaparib combined with endocrine treatments in
      LNCaP are noted. In contrast, we find that the TMPRSS2:ERG fusion-positive cell
      lines VCaP and DuCaP do not show signs of synthetic lethality, but are sensitive
      to cytotoxic effects caused by olaparib. In consequence, additive effects of
      olaparib with endocrine therapy were not observable in these cell lines, showing
      the need for synthetic lethality in combination treatment regimens. Additionally,
      we show that PCa cells remain sensitive to olaparib treatment after initial
      androgen deprivation implicating a possible use of olaparib as maintenance
      therapy. In sum, our preclinical data recommend olaparib as a synthetic lethal
      treatment option in combination or sequenced to first-line endocrine therapy for
      PCa patients with diagnosed BRCAness.

PMID- 29465805
TI  - Corrigendum: Mueller EL, Sabbatini A, Gebremariam A, et al. Why pediatric
      patients with cancer visit the emergency department: United States, 2006-2010.
      Pediatr Blood Cancer. 2015;62:490-495. DOI: 10.1002/pbc.25288.

PMID- 29465804
TI  - In vivo optical imaging of cancer cell function and tumor microenvironment.
AB  - In vivo optical imaging using fluorescence and bioluminescence is superior to
      other methods in terms of spatiotemporal resolution and specificity, and
      represents a new technology for comprehensively studying living organisms in a
      less invasive way. Nowadays, it is an indispensable technology for studying many
      aspects of cancer biology, including dynamic invasion and metastasis. In
      observations of fluorescence or bioluminescence signals in a living body, various
      problems were caused by optical characteristics such as absorption and scattering
      and, therefore, observation of deep tissue was difficult. Recent developments in
      techniques for observation of the deep tissues of living animals overcame this
      difficulty by improving bioluminescent proteins, fluorescent proteins, and
      fluorescent dyes, as well as detection technologies such as two-photon excitation
      microscopy. In the present review, we introduce these technological developments
      and in vivo application of bioluminescence and fluorescence imaging, and discuss
      future perspectives on the use of in vivo optical imaging technology in cancer
      research.

PMID- 29465806
TI  - Principles of haemophilia care: The Asia-Pacific perspective.
AB  - Optimal haemophilia care is best established and implemented through a well
      coordinated plan guided by clearly defined principles and priorities. A document
      which enunciates those details is therefore important. A successful example of
      this approach is the definition of principles of haemophilia care (PHC) outlined
      by the European Association for Haemophilia and Associated Disorders (EAHAD) and
      also the World Federation of Hemophilia. A similar document applicable to the
      Asia-Pacific region must take into account not only the highly varied healthcare
      systems but also the tremendous socio-economic and cultural diversities which
      impact provision of such care. The Asia-Pacific Haemophilia Working Group
      (APHWG), representing the countries in this region, has prepared this perspective
      of the PHC. While endorsing the overall framework outlined by EAHAD, this APHWG
      document emphasizes regional priorities on education and training of healthcare
      personnel in the diagnosis and management of hereditary bleeding disorders.
      Central coordinating agencies with wide stakeholder input, networks of
      haemophilia treatment centres and national registries as well as robust processes
      for procurement and distribution of safe and effective clotting factor
      concentrates (CFCs), implementation of prophylaxis programmes and management of
      patients with inhibitors should also be developed. The implementation of these
      strategies should lead to establishment of good comprehensive care programmes.
      This document should also be an advocacy tool to lobby for improved care for
      people with haemophilia (PWH) in the region. We urge national healthcare policy
      makers to consider these principles and initiate strong and decisive action to
      reach these goals.

PMID- 29465807
TI  - Revisiting Polyarenes and Related Molecules: An Update of Synthetic Approaches
      and Structure-Activity-Mechanistic Correlation for Carcinogenesis.
AB  - A major proportion of basic cause for human cancer has been linked to widespread
      environmental pollutants including analogs of polyarenes. Search of an effective
      therapy can be started with the understanding of the generation of such
      "carcinogens" and their biological interactions. This review is to discuss the
      syntheses, structural activities, mechanistic and biological studies of
      polyarenes such as polycyclic aromatic hydrocarbons (PAHs), polycyclic azaarenes
      (PAAs) and their thia-analogs (PASH). It also summarizes the mechanism of
      mutagenicity and tumorigenicity via metabolic interventions producing diol
      epoxide complexes and eventually formation of DNA adducts. It suggests that
      inhibition of oxidative reactions and formation of diols and epoxides and
      unspecific intracellular activation of cytochrome P450 enzymes could be
      approaches in therapy against such mutagenicity and tumorigenicity. Thus, this
      review reflects that understanding of molecular mechanisms and activations along
      with a clinical and translational medicine approach would require achieving both
      prevention and treatment of this atrocity.

PMID- 29465808
TI  - Investigating the Potential Barrier Function of Nanostructured Materials Formed
      in Engineered Barrier Systems (EBS) Designed for Nuclear Waste Isolation.
AB  - Clay and cement are known nano-colloids originating from natural processes or
      traditional materials technology. Currently, they are used together as part of
      the engineered barrier system (EBS) to isolate high-level nuclear waste (HLW)
      metallic containers in deep geological repositories (DGR). The EBS should prevent
      radionuclide (RN) migration into the biosphere until the canisters fail, which is
      not expected for approximately 103  years. The interactions of cementitious
      materials with bentonite swelling clay have been the scope of our research team
      at the Autonomous University of Madrid (UAM) with participation in several
      European Union (EU) projects from 1998 up to now. Here, we describe the mineral
      and chemical nature and microstructure of the alteration rim generated by the
      contact between concrete and bentonite. Its ability to buffer the surrounding
      chemical environment may have potential for further protection against RN
      migration.

PMID- 29465810
TI  - Sharing the Wealth: ASBMR Journals Update Policies on Data Sharing and Data
      Repositories.

PMID- 29465809
TI  - IDH2 is a novel diagnostic and prognostic serum biomarker for non-small-cell lung
      cancer.
AB  - Lung cancer is the most common leading cause of cancer-related death worldwide.
      Late diagnosis contributes to a high mortality rate and poor survival of this
      cancer. In our previous study, we found that IDH2 polymorphism rs11540478 is a
      risk factor for lung cancer. Here, we examined IDH2 protein expression in culture
      medium in which two non-small-cell lung cancer (NSCLC) cell lines, H460 and A549,
      were growing. We found that the IDH2 protein was elevated in the culture
      supernatant fraction in a time- and cell number-dependent manner. Next, we used
      ELISA methods to examine IDH2 protein level in serum from patients with NSCLC and
      healthy controls. We found that IDH2 protein levels in serum could distinguish
      NSCLC patients from healthy controls with an AUC (area under the curve) of 0.83
      (95% confidence interval = 0.79-0.88). The IDH2 level was decreased in serum from
      NSCLC postsurgical patients compared with the paired presurgical serum. High
      serum IDH2 levels appear to correlate with poor survival in patients with NSCLC.
      These results suggest that IDH2 levels in the serum could be a new effective
      biomarker for the diagnosis and prognosis of NSCLC.

PMID- 29465811
TI  - CK1epsilon and p120-catenin control Ror2 function in noncanonical Wnt signaling.
AB  - Canonical and noncanonical Wnt pathways share some common elements but differ in
      the responses they evoke. Similar to Wnt ligands acting through the canonical
      pathway, Wnts that activate the noncanonical signaling, such as Wnt5a, promote
      Disheveled (Dvl) phosphorylation and its binding to the Frizzled (Fz) Wnt
      receptor complex. The protein kinase CK1epsilon is required for Dvl/Fz
      association in both canonical and noncanonical signaling. Here we show that
      differently to its binding to canonical Wnt receptor complex, CK1epsilon does not
      require p120-catenin for the association with the Wnt5a co-receptor Ror2. Wnt5a
      promotes the formation of the Ror2-Fz complex and enables the activation of Ror2
      bound CK1epsilon by Fz-associated protein phosphatase 2A. Moreover, CK1epsilon
      also regulates Ror2 protein levels; CK1epsilon association stabilizes Ror2, which
      undergoes lysosomal-dependent degradation in the absence of this kinase. Although
      p120-catenin is not required for CK1epsilon association with Ror2, it also
      participates in this signaling pathway as p120-catenin binds and maintains Ror2
      at the plasma membrane; in p120-depleted cells, Ror2 is rapidly internalized
      through a clathrin-dependent mechanism. Accordingly, downregulation of p120
      catenin or CK1epsilon affects late responses to Wnt5a that are also sensitive to
      Ror2, such as SIAH2 transcription, cell invasion, or cortical actin polarization.
      Our results explain how CK1epsilon is activated by noncanonical Wnt and identify
      p120-catenin and CK1epsilon as two critical factors controlling Ror2 function.

PMID- 29465813
TI  - Buschke-Ollendorff syndrome due to a novel LEMD3 mutation - an unusual case of
      alopecia.

PMID- 29465814
TI  - Claramines: A New Class Of Broad-Spectrum Antimicrobial Agents With Bimodal
      Activity.
AB  - The emergence of multidrug-resistant bacteria and pathogens has created an urgent
      need for the development of new antibiotics. Herein we report our investigations
      into the broad-spectrum activity of an easily prepared water-soluble
      polyaminosterol compound, namely claramine A1, against both drug-sensitive and
      drug-resistant Gram-negative and Gram-positive bacterial strains. We also report
      its peculiar mechanism of action, which differs from that of all the other well
      known classes of antibiotics, toward Gram-negative and Gram-positive bacteria.
      Given their low cytotoxicity, this class of compounds based on claramine A1 could
      constitute an effective response to combat the emergence of multidrug-resistant
      bacteria and nosocomial diseases.

PMID- 29465812
TI  - The role of salt for immune cell function and disease.
AB  - The immune system evolved to protect organisms from invading pathogens. A network
      of pro- and anti-inflammatory cell types equipped with special effector molecules
      guarantees efficient elimination of intruders like viruses and bacteria. However,
      imbalances can lead to an excessive response of effector cells incurring
      autoimmune or allergic diseases. An interplay of genetic and environmental
      factors contributes to autoimmune diseases and recent studies provided evidence
      for an impact of dietary habits on the immune status and related disorders.
      Western societies underwent a change in lifestyle associated with changes in food
      consumption. Salt (sodium chloride) is one component prevalent in processed food
      frequently consumed in western countries. Here we summarize recent advances in
      understanding the mechanisms behind the effects of sodium chloride on immune
      cells like regulatory T cells (Tregs) and T helper (TH ) 17 cells and its
      implication as a risk factor for several diseases.

PMID- 29465815
TI  - Revealing the Transient Concentration of CO2 in a Mixed-Matrix Membrane by IR
      Microimaging and Molecular Modeling.
AB  - Through IR microimaging the spatially and temporally resolved development of the
      CO2 concentration in a ZIF-8@6FDA-DAM mixed matrix membrane (MMM) was visualized
      during transient adsorption. By recording the evolution of the CO2 concentration,
      it is observed that the CO2 molecules propagate from the ZIF-8 filler, which acts
      as a transport "highway", towards the surrounding polymer. A high-CO2 
      concentration layer is formed at the MOF/polymer interface, which becomes more
      pronounced at higher CO2 gas pressures. A microscopic explanation of the origins
      of this phenomenon is suggested by means of molecular modeling. By applying a
      computational methodology combining quantum and force-field based calculations,
      the formation of microvoids at the MOF/polymer interface is predicted. Grand
      canonical Monte Carlo simulations further demonstrate that CO2 tends to
      preferentially reside in these microvoids, which is expected to facilitate CO2
      accumulation at the interface.

PMID- 29465816
TI  - Crystalline Radicals Derived from Classical N-Heterocyclic Carbenes.
AB  - One-electron reduction of C2-arylated 1,3-imidazoli(ni)um salts (IPrAr )Br
      (Ar=Ph, 3 a; 4-DMP, 3 b; 4-DMP=4-Me2 NC6 H4 ) and (SIPrAr )I (Ar=Ph, 4 a; 4-Tol,
      4 b) derived from classical NHCs (IPr=:C{N(2,6-iPr2 C6 H3 )}2 CHCH, 1;
      SIPr=:C{N(2,6-iPr2 C6 H3 )}2 CH2 CH2 , 2) gave radicals [(IPrAr )]. (Ar=Ph, 5 a;
      4-DMP, 5 b) and [(SIPrAr )]. (Ar=Ph, 6 a; 4-Tol, 6 b). Each of 5 a,b and 6 a,b
      exhibited a doublet EPR signal, a characteristic of monoradical species. The
      first solid-state characterization of NHC-derived carbon-centered radicals 6 a,b
      by single-crystal X-ray diffraction is reported. DFT calculations indicate that
      the unpaired electron is mainly located at the original carbene carbon atom and
      stabilized by partial delocalization over the adjacent aryl group.

PMID- 29465817
TI  - Spectroscopic and Hydrodynamic Characterisation of DNA-Linked Gold Nanoparticle
      Dimers in Solution using Two-Photon Photoluminescence.
AB  - Two-photon photoluminescence (TPPL) emission spectra of DNA-gold nanoparticle
      (AuNP) monoconjugates and the corresponding DNA-linked AuNP dimers are obtained
      by photon time-of-flight spectroscopy. This technique is combined with two-photon
      photoluminescence fluctuation correlation spectroscopy (TPPL-FCS) to
      simultaneously monitor the optical and hydrodynamic behaviour of these nano
      assemblies in solution, with single-particle sensitivity and microsecond temporal
      resolution. In this study, the AuNPs have an average core diameter of 12 nm,
      which renders their dark-field plasmonic light scattering too weak for single
      particle imaging. Moreover, as a result of the lack of plasmonic coupling in the
      dimers, the optical extinction, scattering and photoluminescence spectra of the
      DNA-AuNP complexes are not sufficiently different to distinguish between monomers
      and dimers. The use of TPPL-FCS successfully addresses these bottlenecks and
      enables the distinction between AuNP monomers and AuNP dimers in solution by
      measurement of their hydrodynamic rotational and translational diffusion.

PMID- 29465818
TI  - Calcineurin is required for male sex pheromone biosynthesis and female
      acceptance.
AB  - Lepidoptera sex pheromone biosynthesis is regulated by pheromone biosynthesis
      activating neuropeptide (PBAN). PBAN regulates not only female sex pheromone
      biosynthesis but also male sex pheromone biosynthesis. Previous research has
      confirmed that PBAN regulates sex pheromone biosynthesis using Ca2+ as a
      secondary messenger in all examined species to date. However, the downstream
      signal of Ca2+ has remained elusive. In the present study, calcineurin A (CNA), a
      downstream signal of Ca2+ , was discovered in Helicoverpa armigera male
      hairpencil and named HaCNA. Sequence analysis demonstrated that the open reading
      frame of HaCNA contains 1488 nucleotides encoding 495 amino acid residues. A
      homology search revealed that HaCNA shares a high amino acid identity with the
      CNA of other insects. Developmental and spatial expression analyses revealed that
      the mRNA levels of HaCNA peaked at 24 h after emergence and that HaCNA expression
      was ubiquitous in all examined tissues. Activity analysis revealed that PBAN
      activates HaCNA, and a Ca2+ inhibitor, Lacl3 , attenuated the effect of PBAN by
      decreasing HaCNA activity. Pharmacological inhibitor and RNA interference
      mediated knockdown assays revealed that both activity inhibition and decreased
      mRNA levels of HaCNA led to a significant decrease in the production of the male
      sex pheromone components [octadecanol and (Z)-11 hexadecanol)] and in the
      efficacy of female mating acceptance. Our results demonstrate that HaCNA acts as
      downstream signal of PBAN/Ca2+ and plays an important role in PBAN-induced male
      sex pheromone biosynthesis and female mating acceptance.

PMID- 29465819
TI  - High resolution SEM characterization of nano-precipitates in ODS steels.
AB  - The performance of the present-day scanning electron microscopy (SEM) extends far
      beyond delivering electronic images of the surface topography. Oxide dispersion
      strengthened (ODS) steel is on of the most promising materials for the future
      nuclear fusion reactor because of its good radiation resistance, and higher
      operation temperature up to 750 degrees C. The microstructure of ODS should not
      exceed tens of nm, therefore there is a strong need in a fast and reliable
      technique for their characterization. In this work, the results of low-kV SEM
      characterization of nanoprecipitates formed in the ODS matrix are presented.
      Application of highly sensitive photo-diode BSE detector in SEM imaging allowed
      for the registration of single nm-sized precipitates in the vicinity of the ODS
      alloys. The composition of the precipitates has been confirmed by TEM-EDS.

PMID- 29465820
TI  - Literally Green Chemical Synthesis of Artemisinin from Plant Extracts.
AB  - Active pharmaceutical ingredients are either extracted from biological sources
      where they are synthesized in complex, dynamic environments-or prepared in
      stepwise chemical syntheses by reacting pure reagents and catalysts under
      controlled conditions. A combination of these two approaches, where plant
      extracts containing reagents and catalysts are utilized in intensified chemical
      syntheses, creates expedient and sustainable processes. We illustrate this
      principle by reacting crude plant extract, oxygen, acid, and light to produce
      artemisinin, a key active pharmaceutical ingredient of the most powerful
      antimalarial drugs. The traditionally discarded extract of Artemisia annua plants
      contains dihydroartemisinic acid-the final biosynthetic precursor-as well as
      chlorophyll, which acts as a photosensitizer. Efficient irradiation with visible
      light in a continuous-flow setup produces artemisinin in high yield, and the
      artificial biosynthetic process outperforms syntheses with pure reagents.

PMID- 29465821
TI  - Quantitative magnetic resonance spectroscopy at 3T based on the principle of
      reciprocity.
AB  - Quantification of magnetic resonance spectroscopy signals using the phantom
      replacement method requires an adequate correction of differences between the
      acquisition of the reference signal in the phantom and the measurement in vivo.
      Applying the principle of reciprocity, sensitivity differences can be corrected
      at low field strength by measuring the RF transmitter gain needed to obtain a
      certain flip angle in the measured volume. However, at higher field strength the
      transmit sensitivity may vary from the reception sensitivity, which leads to
      wrongly estimated concentrations. To address this issue, a quantification
      approach based on the principle of reciprocity for use at 3T is proposed and
      validated thoroughly. In this approach, the RF transmitter gain is determined
      automatically using a volume-selective power optimization and complemented with
      information from relative reception sensitivity maps derived from contrast
      minimized images to correct differences in transmission and reception
      sensitivity. In this way, a reliable measure of the local sensitivity was
      obtained. The proposed method is used to derive in vivo concentrations of brain
      metabolites and tissue water in two studies with different coil sets in a total
      of 40 healthy volunteers. Resulting molar concentrations are compared with
      results using internal water referencing (IWR) and Electric REference To access
      In vivo Concentrations (ERETIC). With the proposed method, changes in coil
      loading and regional sensitivity due to B1 inhomogeneities are successfully
      corrected, as demonstrated in phantom and in vivo measurements. For the tissue
      water content, coefficients of variation between 2% and 3.5% were obtained (0.6
      1.4% in a single subject). The coefficients of variation of the three major
      metabolites ranged from 3.4-14.5%. In general, the derived concentrations agree
      well with values estimated with IWR. Hence, the presented method is a valuable
      alternative for IWR, without the need for additional hardware such as ERETIC and
      with potential advantages in diseased tissue.

PMID- 29465822
TI  - MSN-on-a-Chip: Cell-Based Screenings Made Possible on a Small-Molecule Microarray
      of Native Natural Products.
AB  - Standard small-molecule microarrays (SMMs) are not well-suited for cell-based
      screening assays. Of the few attempts made thus far to render SMMs cell
      compatible, all encountered major limitations. Here we report the first
      mesoporous silica nanoparticle (MSN)-on-a-chip platform capable of allowing high
      throughput cell-based screening to be conducted on SMMs. By making use of a glass
      surface on which hundreds of MSNs, each encapsulated with a different native
      natural product, were immobilized in spatially defined manner, followed by on
      chip mammalian cell growth and on-demand compound release, high-content screening
      was successfully carried out with readily available phenotypic detection methods.
      By combining this new MSN-on-a-chip system with small interfering RNA technology
      for the first time, we discovered that (+)-usniacin possesses synergistic
      inhibitory properties similar to those of olaparib (an FDA-approved drug) in
      BRCA1-knockdown cancer cells.

PMID- 29465823
TI  - Differential expression of various clones of estrogen receptor in cell block
      preparation of lung adenocarcinoma.
AB  - BACKGROUND: Women treated for breast cancer are at increased risk of developing
      pulmonary nodules which could represent new primary lung carcinomas or metastatic
      breast carcinoma. The FNA biopsy is frequently the first diagnostic choice in
      determining the primary site of the tumor. Estrogen receptor (ER) positivity in
      diagnostic tissue is generally used to favor breast over lung primary. However,
      the recent studies have shown a wide range of ER antibody cross reactivity with
      lung adenocarcinoma. We studied the frequency of ER expression in cytology
      samples of lung adenocarcinoma using antibodies to three different ER clones.
      METHODS: Cytology cell block preparations, including 22 lung FNAs and 19
      malignant pleural effusions (PE) from 41 patients, with clinically documented
      primary lung adenocarcinomas were selected for this study. All cases were stained
      with monoclonal antibodies to ER clones 6F11 and 1D5. Twenty nine cases with
      remaining available material (15 FNA and 14 PE) were stained with a third
      antibody to ER clone SP1. The extent of ER nuclear staining was scored as 3+ (50%
      100% of tumor cells), 2+ (11%-49%), and 1+ (<=10%). RESULTS: Positivity for ER
      6F11 clone was present in 4 of 22 lung FNAs (18.2%, 2+ staining). Two of the four
      6F11 positive FNAs also co-expressed ER-1D5 (9.1%, 2+ staining). No
      immunoreactivity was observed for ER clones 6F11 and 1D5 in all 19 malignant PEs.
      In addition, none of the remaining 15 FNAs and 14 PEs showed immunoreactivity for
      ER-SP1 clone. CONCLUSIONS: A small subset of pulmonary adenocarcinomas shows
      immunoreactivity for ER clones 6F11 and 1D5 in FNA samples (18.2% and 9.1%,
      respectively). The absence of immunoreactivity for ER-SP1 clone indicates higher
      specificity of this clone in non-breast tissue. The differential diagnostic value
      of all ER clones in malignant PEs appears to be secure. Larger studies are
      necessary to validate this observation.

PMID- 29465824
TI  - Left ventricular chamber geometry in cardiomyopathies: insights from a
      computerized anatomical study.
AB  - AIMS: Some authors have hypothesized that left ventricular chamber dilatation in
      ischaemic and idiopathic cardiomyopathies results in spherical transformation.
      Aiming to characterize how this transformation occurs, a study was performed by
      comparing normal and dilated specimens regarding sphericity and proportionality
      in left heart chambers. It is important to provide data for the development of
      therapeutic strategies in these diseases. METHODS AND RESULTS: An anatomical
      study was performed by comparing normal (n = 10), ischaemic (n = 15), and
      idiopathic (n = 18) dilated human cardiomyopathic specimens regarding left
      ventricular chambers and their segmental proportionality to normal hearts. It was
      performed by capturing and processing images with proper software in three
      different levels of left ventricular chamber (basal, equatorial, and apical).
      These obtained data were analysed based on sphericity and proportionality by two
      dedicated indexes. Spherical shape: Calculated segmental indexes showed that
      dilated specimens were not spherical because they were smaller than as expected
      for a spherical shape (all values were <70% of a perfect sphere).
      Proportionality: There was no difference between basal index perimeters among
      groups, but apical index was lower in dilated specimens than in normal hearts,
      and so dilatation was not proportional to normal hearts. CONCLUSIONS: Left
      ventricular chambers of anatomical specimens with dilated cardiomyopathies did
      not display a spherical shape and were not proportional to normal hearts.

PMID- 29465827
TI  - Highly Stable Lithium Metal Batteries Enabled by Regulating the Solvation of
      Lithium Ions in Nonaqueous Electrolytes.
AB  - Safe and rechargeable lithium metal batteries have been difficult to achieve
      because of the formation of lithium dendrites. Herein an emerging electrolyte
      based on a simple solvation strategy is proposed for highly stable lithium metal
      anodes in both coin and pouch cells. Fluoroethylene carbonate (FEC) and lithium
      nitrate (LiNO3 ) were concurrently introduced into an electrolyte, thus altering
      the solvation sheath of lithium ions, and forming a uniform solid electrolyte
      interphase (SEI), with an abundance of LiF and LiNx Oy on a working lithium metal
      anode with dendrite-free lithium deposition. Ultrahigh Coulombic efficiency
      (99.96 %) and long lifespans (1000 cycles) were achieved when the FEC/LiNO3
      electrolyte was applied in working batteries. The solvation chemistry of
      electrolyte was further explored by molecular dynamics simulations and first
      principles calculations. This work provides insight into understanding the
      critical role of the solvation of lithium ions in forming the SEI and delivering
      an effective route to optimize electrolytes for safe lithium metal batteries.

PMID- 29465828
TI  - A large mass and erythematous-violaceous plaques.

PMID- 29465826
TI  - Effect of caloric restriction on depression.
AB  - Recently, most of evidence shows that caloric restriction could induce
      antidepressant-like effects in animal model of depression. Based on studies of
      the brain-gut axis, some signal pathways were common between the control of
      caloric restriction and depression. However, the specific mechanism of the
      antidepressant-like effects induced by caloric restriction remains unclear.
      Therefore, in this article, we summarized clinical and experimental studies of
      caloric restriction on depression. This review may provide a new therapeutic
      strategy for depression.

PMID- 29465829
TI  - [Spatio-temporal variation of the ichthyofauna in Xel-Ha, Mexican Caribbean
      Marine Park and its relationship to physico-chemical parameters].
AB  - Xel-Ha is a private marine park where the extraction of flora and fauna is not
      allowed. Here, reef fish are one of the main touristic attractions, but there are
      no published surveys focused on fish community in this site. In this study we
      analyzed the spatio-temporal variation of the fish community in different areas
      of the marine park Xel-Ha. Abundance and richness were estimated during one-year
      period (2012-2013); visual censuses using fixed transects of 100x5 m each
      distributed in 21 transects along five sites were established in different zones:
      "Bocana", "Center", "North branch", "Cave" and "River", including the inlet mouth
      to the sea, brackish mangrove channels and a zone with freshwater influence. To
      characterize the fish community, we used species richness, abundance, diversity,
      and density compared among zones and climatic seasons (rain, "norths" and dry).
      The similarity among zones and seasons was estimated using a multidimensional
      scaling analysis. The replacement on the species composition among seasons and
      sites was realized based on the presence-absence of fish. The influence of
      physicochemical variables such as temperature, salinity and dissolve oxygen
      concentration in the fish community was estimated by a principal component
      analysis. A total of 22 641 individuals were recorded corresponding to sixty
      three species over the year. Abundance was higher during the windy season
      (locally named "norths") with 7 991 organisms. The most representative species
      according with abundance and frequency of occurrence were: Haemulon sciurus, H.
      flavolineatum, Lutjanus griseus, Acanthurus coeruleus, Abudefduf saxatilis, and
      Gerres cinereus. Diversity increased from the rainy to the dry season; species
      richness and diversity was lower in "River" than other sites in Xel-Ha. Most
      species (54 %) species were residents through the year. Four non-shared species
      were observed during the rainy season and three in dry season. Dissolved oxygen
      was the most influential variable on the fish community composition among zones.
      Xel-Ha houses nearly 20 % of fish biodiversity reported for the mexican
      Caribbean, and the predominance of juveniles of several species confirms its role
      as a nursery area.

PMID- 29465831
TI  - Loss-of-function mutations in filaggrin gene and malignant melanoma.

PMID- 29465832
TI  - Human papillomavirus and immunosuppressive drugs in dermatology - a 'neoplastic'
      combination?

PMID- 29465833
TI  - Dermatoporosis: a further step to recognition.

PMID- 29465830
TI  - Toll-like receptor 3 signal augments radiation-induced tumor growth retardation
      in a murine model.
AB  - Radiotherapy induces anti-tumor immunity by induction of tumor antigens and
      damage-associated molecular patterns (DAMP). DNA, a representative DAMP in
      radiotherapy, activates the stimulator of interferon genes (STING) pathway which
      enhances the immune response. However, the immune response does not always
      parallel the inflammation associated with radiotherapy. This lack of
      correspondence may, in part, explain the radiation-resistance of tumors. Additive
      immunotherapy is expected to revive tumor-specific CTL facilitating radiation
      resistant tumor shrinkage. Herein pre-administration of the double-stranded RNA,
      polyinosinic-polycytidylic acid (polyI:C), in conjunction with radiotherapy, was
      shown to foster tumor suppression in mice bearing radioresistant, ovalbumin
      expressing Lewis lung carcinoma (LLC). Extrinsic injection of tumor antigen was
      not required for tumor suppression. No STING- and CTL-response was induced by
      radiation in the implant tumor. PolyI:C was more effective for induction of tumor
      growth retardation at 1 day before radiation than at post-treatment. PolyI:C
      targeted Toll-like receptor 3 with minimal effect on the mitochondrial antiviral
      signaling protein pathway. Likewise, the STING pathway barely contributed to LLC
      tumor suppression. PolyI:C primed antigen-presenting dendritic cells in draining
      lymph nodes to induce proliferation of antigen-specific CTL. By combination
      therapy, CTL efficiently infiltrated into tumors with upregulation of relevant
      chemokine transcripts. Batf3-positive DC and CD8+ T cells were essential for
      therapeutic efficacy. Furthermore, polyI:C was shown to stimulate tumor
      associated macrophages and release tumor necrosis factor alpha, which acted on
      tumor cells and increased sensitivity to radiation. Hence, polyI:C treatment
      prior to radiotherapy potentially induces tumor suppression by boosting CTL
      dependent and macrophage-mediated anti-tumor responses. Eventually, polyI:C and
      radiotherapy in combination would be a promising therapeutic strategy for
      radiation-resistant tumors.

PMID- 29465835
TI  - Doolin Lecture 2017: Dancing away from the Crossroads: Rhona Mahony.

PMID- 29465834
TI  - Targeted Delivery of an Activatable Fluorescent Probe for the Detection of Furin
      Activity in Living Cells.
AB  - Furin, a protein convertase, plays a crucial role in the progression of tumors.
      In this work, a new fluorescent probe consisting of a peptide, Arg-Val-Arg-Arg
      (RVRR), and an aminoluciferin fluorophore was designed and prepared for the
      responsive and activatable detection of furin activity in vitro and in living
      cells. We demonstrated that this probe could be responsive toward furin with an
      "off-on" florescence signal and generated an approximately 3.58-fold enhancement
      in the fluorescence intensity in vitro. Fluorescence imaging in MDA-MB-468 and
      LoVo cells showed that the probe could be cleaved by overexpressed furin with
      fluorescence turn-on in MDA-MB-468 cells, and this probe was also found to be
      capable of discriminating between furin-overexpressing and furin-deficient cell
      lines. Our research indicates that this probe has great potential for the
      detection of furin activity in living cells.

PMID- 29465836
TI  - The Role of Screening for Coeliac Disease in Asymptomatic Individuals.

PMID- 29465837
TI  - Post-Chemotherapy Retroperitoneal Lymph Node Dissection in Patients with Non
      Seminomatous Germ Cell Tumour (NSGCT).
AB  - Diabetic retinopathy is a significant complication of diabetes, and the most
      common cause of blindness in people under the age of 65. The National Diabetic
      Retinal Screening Programme (Diabetic RetinaScreen) was established to detect
      sight threatening retinopathies. The purpose of this cross-sectional study is to
      determine the barriers to the uptake of Diabetic RetinaScreen, to investigate
      discrepancies in attendance, if any, between patients whose diabetes care is
      delivered in a large tertiary referral hospital out-patient setting or in general
      practice, and to evaluate general practitioner&apos;s satisfaction with the
      service. Older age (OR 1.023, 95% CI 1.001 to 1.046) and complications of
      diabetes, excluding ocular complications, (OR 2.741, 95% CI 1.158 to 6.489) were
      associated with increased attendance at Diabetic RetinaScreen. Online referral is
      now available and the preferred method of referral. Efforts to encourage younger
      patients who do not yet have complications of diabetes may be beneficial.

PMID- 29465838
TI  - An Analysis of Gender Diversity in Urology in the UK and Ireland.
AB  - Traditionally, surgery and certain surgical sub-specialities in particular have
      been predominantly male orientated. In recent years, there has been an increased
      proportion of female medical graduates which will ultimately have an effect on
      speciality choices. The aim of this study was to assess the gender diversity
      among urologists in the UK and Ireland. The total number and gender breakdown of
      consultant urologists and trainees in the UK and Ireland was obtained from the
      British Association of Urological Surgeons (BAUS) and the Irish Society of
      Urology (ISU) membership offices. The total number and gender breakdown of
      medical school entrants and graduates in 2015 was obtained from the six medical
      schools in the Republic of Ireland. There are a total of 1,012 consultant
      urologists in the UK and Ireland. In the UK, 141 (14.6%) are female compared to
      four (8.2%) in Ireland, p= 0.531. There was a significant increase in the number
      of females between consultant urologists and trainees in both the UK (p=0.0001)
      and Ireland (p=0.015). In recent years, there has been a significant change in
      the percentage of female trainees in the UK and Ireland (22.8% (n=75) in 2011 vs
      31.7% (n=93) in 2014, p=0.019. Between the six medical schools in Ireland, there
      were significantly more female entrants (n=726, 56.5%) than female graduates
      (n=521, 51.2%) in 2015, p=0.013.There has been a significant shift in gender
      diversity in urology in the UK and Ireland. Efforts to increase diversity should
      be pursued to attract further trainees to urology.

PMID- 29465839
TI  - Vitamin D Insufficiency in Patients Undergoing Total Knee Arthroplasty in
      Ireland.
AB  - Introduction: Vitamin D is essential for bone health. We aimed to assess the
      vitamin D levels of patients undergoing total knee arthroplasty TKA). Methods:
      All TKA patients during a calendar year had their 25-hydroxyvitamin-D3 (25-OH-D3)
      assay levels assessed pre and post operatively. A control group comprising of
      patients admitted for 1-day general medical assessment was recruited. Usage of
      supplements containing Vitamin D was recorded for both groups. Results: There was
      no evidence of a difference in Vitamin D levels between the TKA group and the
      control group (p=0.19). Just over 40% of patients had insufficient levels of
      vitamin D in the TKA group (50 nmol/L cut off). There was a statistically
      significant drop in vitamin D levels post operatively (p=0.0001). Supplements
      were protective against insufficiency post operatively (p=0.0005, OR 6.0985).
      Discussion: This study documents a high prevalence of vitamin D insufficiency in
      patients undergoing TKA surgery. Our results suggest a consumption of 25-OH-D3 as
      part of the surgical insult.

PMID- 29465840
TI  - Post Stroke Fatigue; Point Prevalence, Characterization, Associations and
      Radiological Correlation in a Rehabilitation Hospital.
AB  - Post stroke fatigue (PSF) is a frequently reported symptom by stroke survivors
      undergoing rehabilitation. This cross sectional observational study was
      undertaken in a rehabilitation facility to look at its prevalence and
      relationship with various variables like personal factors, type of stroke, social
      context, hemispheric involvement on CT scan and mobility status. The results
      showed that PSF was present in 83% (25 out of 30) of the patients included in the
      study. No clear association could be established between PSF, social,
      radiological and functional characteristics.

PMID- 29465841
TI  - Permanent Childhood Hearing Impairment: Aetiological Evaluation of Infants
      identified through the Irish Newborn Hearing Screening Programme.
AB  - The Newborn Hearing Screening Programme (NHSP) was established in Cork University
      Maternity Hospital (CUMH) in April 2011. Between April 2011 and July 2014, 42
      infants were identified with a Permanent Childhood Hearing Impairment (PCHI).
      Following this diagnosis, infants underwent a paediatric assessment according to
      recognised guidelines with the intention of identifying the underlying aetiology
      of the PCHI. The aim of this study was to assess the findings of this
      aetiological workup via retrospective chart review. PCHI data was obtained from
      the eSP database. This is a web based information system (eSP) used to track each
      baby through the screening and referral process A retrospective chart review of
      these patients was performed. Sixteen (38%) infants were diagnosed with a
      bilateral sensorineural hearing loss. Two infants had congenital CMV infection. A
      Connexin 26 gene mutation was detected in one infant. Two infants were diagnosed
      with Waardenburg syndrome, One with Pendred syndrome and one with Pfeiffer
      syndrome. Five babies underwent cochlear implantation. Through adherence to the
      recommended protocol a possible cause of PCHI may be determined. This study has
      identified areas of future improvement for this service in Ireland.

PMID- 29465842
TI  - Paediatric Consultation Liaison Psychiatry Services (PCLPS) -what are they
      actually doing?
AB  - Introduction Paediatric Consultation Liaison Psychiatry Services (PCLPS) are
      specialised services treating mental health difficulties co-morbid with medical
      problems. Methods Standardised clinical data was retrieved from all case notes
      (N=108) during the study timeframe (Jan-June 2016). Results The majority of
      children were female 59 (55%) with a mean age of 13. Presentation was typically
      via the Emergency Department (ED) (85, 79%), and of those, the majority (53, 62%)
      were 'out of hours' and for Deliberate Self-harm (44, 52%) Almost half of all
      cases seen (50, 46%) were previously known, and discharged back (84, 78%), to
      CAMHS. Discussion The majority of work conducted by the PCLPS involved children
      with acute or deteriorating psychiatry disorders, previously known to CAMHS, with
      a much smaller focus on typical liaison presentations. Adequate resourcing of
      hospital based PCLPS and 'out of hours' CAMHS are necessary to allow PCLPS
      provide a specialist service to children with combined medical and MH problems.
      Given the development of the National Children's Hospital, addressing these
      resourcing deficits is of vital importance.

PMID- 29465843
TI  - Awareness of Medical Fitness to Drive Guidelines among Occupational Physicians
      and Psychiatrists.
AB  - Irrespective of national guidelines for medical fitness to drive, this study
      investigated the cumulative expert wisdom of clinicians regarding minimum periods
      of driving cessation required for patients suffering from conditions that can
      impair driver capability. Occupational Physicians (196) and Psychiatrists (103)
      completed an online questionnaire. For private motorists, the modal response for
      anxiety and depression favoured clinical discretion, followed by three month
      cessations for hypomania, acute psychosis, schizophrenia and alcohol dependence
      and six weeks for alcohol misuse/dependence. For professional drivers the modal
      value for anxiety and depression was three months, rising to six months for
      hypomania, psychosis and schizophrenia and 12 months for both alcohol
      misuse/dependence. Chi-square test results indicated statistically significant
      differences in clinical opinion between Occupational Physicians and Psychiatrists
      regarding driving cessation times for drivers suffering from psychiatric and
      alcohol misuse conditions except for alcohol dependence. Further studies are
      warranted to investigate these issues in more depth.

PMID- 29465844
TI  - Oocyte Donation Pregnancies- Non-Disclosure of Oocyte Recipient Status to
      Obstetric Care Providers and Perinatal Outcomes.
AB  - Background: Oocyte donation pregnancies- non-disclosure of oocyte recipient (OR)
      status to obstetric care providers and perinatal outcomes.Many studies report a
      higher rate of pregnancy-induced hypertension (PIH) and severe pre-eclampsia
      (PET) in OR pregnancies. The objective is to determine the rates of non
      disclosure of OR pregnancy to obstetric care providers and also the rates of
      perinatal complications. Method: This was a retrospective review of all oocyte
      recipient (OR) pregnancies, who subsequently delivered at Cork University
      Maternity Hospital, between 2007- 2012 inclusive. Obstetric case notes were
      reviewed to investigate perinatal outcomes and whether OR status had been
      documented (unambiguously, in code or not at all). Results: Less than one-third
      (30.2%; n=32/106) had unambiguous documentation, one-third (33%; n=35/106) had no
      documentation and the remainder (36.8%; n=39/106) had a code familiar only to
      their obstetrician. There was a high rate of gestational hypertensive disorders
      (28.3%; n= 30), most frequently occurring with multiple gestation. Discussion:
      There was a low rate of clear documentation of OR status. Gestational
      hypertensive disorders occurred with increased frequency.

PMID- 29465845
TI  - A Study To Assess The Prevalence Of Exercise-Induced Bronchoconstriction In Inter
      County Hurling.
AB  - Exercise-Induced Bronchoconstriction (EIB) is an acute, transient airway
      narrowing occurring after exercise which may impact athletic performance. Studies
      report 10% of the general population and up to 90% of asthmatics experience EIB.
      Ninety-two players from three elite hurling squads underwent a spirometric field
      based provocation test with real-time heart rate monitoring and lactate
      measurements to ensure adequate exertion. Players with a new diagnosis of EIB and
      those with a negative field-test but with a previous label of EIB or asthma
      underwent further reversibility testing and if negative, methacholine challenge.
      Eight (8.7%) of players had EIB, with one further athlete having asthma with a
      negative field test. Interestingly, only three out of 12 players who had
      previously been physician-labelled with EIB or asthma had their diagnosis
      objectively confirmed. Our study highlights the role of objective testing in EIB.

PMID- 29465846
TI  - Isolated Unilateral Pulmonary Artery Agenesis complicated by Symptomatic
      Aspergilloma.
AB  - Isolated unilateral pulmonary artery agenesis is a rare diagnosis. Poor blood
      flow to the lung parenchyma renders the tissue susceptible to opportunistic
      infections. We present the unusual case of isolated unilateral pulmonary artery
      agenesis complicated by aspergilloma. Management options and considerations are
      discussed.

PMID- 29465847
TI  - Dysphagia in the Elderly Following Anterior Cervical Surgery: A Multidisciplinary
      Approach.
AB  - Dysphagia is a risk factor for adverse health outcomes like aspiration, recurrent
      chest infections and malnutrition. Here, we describe a case of an 82-year-old
      lady who presented with a two-month history of dysphagia after an anterior
      odontoid screw fixation for a type II odontoid process fracture. This case
      highlights the importance of a multidisciplinary approach to patient care.

PMID- 29465848
TI  - The Avocado Hand.
AB  - Accidental self-inflicted knife injuries to digits are a common cause of tendon
      and nerve injury requiring hand surgery. There has been an apparent increase in
      avocado related hand injuries. Classically, the patients hold the avocado in
      their non-dominant hand while using a knife to cut/peel the fruit with their
      dominant hand. The mechanism of injury is usually a stabbing injury to the non
      dominant hand as the knife slips past the stone, through the soft avocado fruit.
      Despite their apparent increased incidence, we could not find any cases in the
      literature which describe the "avocado hand". We present a case of a 32-year-old
      woman who sustained a significant hand injury while preparing an avocado. She
      required exploration and repair of a digital nerve under regional anaesthesia and
      has since made a full recovery.

PMID- 29465849
TI  - Interventions to Improve the Treatment of Malaria in an Acute Teaching Hospital
      in Ireland.
AB  - Malaria is the most serious parasitic infection. At our institution over a two
      year period there were treatment errors in 18% (n=3) of cases. The aim of this
      multidisciplinary study was to ensure appropriate and timely treatment of malaria
      by implementation of a cluster of interventions: reconfiguration of existing
      guidelines, provision of prescribing information; delivery of education sessions
      to front-line staff and enabling rapid access to medication. Staff feedback was
      assessed through a questionnaire. Perceived benefits gained included awareness of
      guidelines (91%, n= 39), how to diagnose (81%, n =35), how to treat (86%, n=37),
      that treatment must be prompt (77%, n=33) and where to find treatment out of
      hours (84%, n=36). 'Others' perceived benefits (5% n= 2) noted referred to
      treatment in pregnancy. Going forward, a programme of on-going staff education,
      repeated audits of guideline compliance and promotion of reporting of medication
      errors should help ensure that these benefits are sustained.

PMID- 29465850
TI  - Incorporating Oral Health as Part of Routine Diabetes Care in Ireland.
AB  - Diabetes mellitus is a common disorder of glucose metabolism that is increasingly
      prevalent in the Irish population. It is associated with a range of complications
      leading to substantial morbidity and mortality. A less well-recognized
      complication of diabetes is periodontal disease. This is a chronic inflammatory
      disease affecting the periodontium, the specialized group of tissues that
      surround and support the teeth, including the gingiva (gums) and alveolar bone.
      Periodontal disease affects patients with diabetes with a greater prevalence and
      incidence than non-diabetic patients, and can itself exert negative effects on
      glucose control in people with diabetes. The National Clinical Programme for
      Diabetes in Ireland aims to reduce the morbidity and mortality associated with
      diabetes, which includes the development and dissemination of guidelines
      supporting integrated care. Based on the bidirectional relationship between
      diabetes mellitus and periodontal disease, we recommend that an oral health
      evaluation, as well as any necessary onward referral, be incorporated into the
      Irish recommendations for routine diabetes care, as part of the National Clinical
      Programme.

PMID- 29465851
TI  - The Variables Affecting Decision-making Factors & Outcomes in Salvage versus
      Amputation for Complex Limb Injuries.

PMID- 29465852
TI  - A Case of Postpartum HELLP Syndrome.

PMID- 29465853
TI  - New Delhi Metallo-beta-Lactamase-Producing Carbapenem-Resistant Enterobacteriacae
      Isolated From Bronchial Washings.

PMID- 29465854
TI  - Teaching Musculoskeletal Medicine to Undergraduate Students in a Simulated
      Environment.

PMID- 29465855
TI  - Responses to spread of.Ebola virus disease epidemic in West Africa: A review.
AB  - BACKGROUND: The first Ebola virus disease (EVD) epidemic in West Africa is
      unprecedented in its spread, complexity and severity. Comparing responses to
      spread of the virus in the three most affected countries - Guinea, Sierra Leone
      and Liberia- with that in Nigeria, Senegal and Mali where the epidemic was
      quickly brought under control may guide future mitigation efforts. METHODS:
      Literature from Pubmed. Google,Center for Disease Control and Prevention (CDC),
      Morbidity and Mortality Weekly Report (MMWR), World Health Organization's Updates
      and Ebola Response Reports: Results: The epidemic spread undiagnosed for three
      months from Meliandou in Guinea to its four rural prefectures and its. capital
      Conakry, two countires in Liberia and two districts in Sierra Leone. Control
      measures were hampered by traditional and faith healers offering -inappropriate
      treatments, as well as secret societies encouraging unsafe burial rituals.
      Whereas, in Nigeria, a case imported from Liberia on 20 July 2014 was diagnosed
      on the 3rd day; all primary, secondary and tertiary contacts were traced. Also,
      at a formal meeting, officials of Lagos state government discouraged treatment of
      EVD by faith healers. In Senegal, a single case imported from Guinea on 20 August
      2014 was diagnosed on the 9th day, treated and further spread was prevented. In
      Mali, there were two waves of transmissions identified on 23 October and 12
      November 2014 within 15 days of importation and the epidemic was controlled.There
      were no cases of EVD treated by any traditional healers or faith healers in
      Nigeria, Senegal and Mali. CONCLUSION: Education of traditional and faith healers
      on EVD will complement control measures for EVD epidemic.

PMID- 29465856
TI  - Bacteriology of middle meatal aspirate of adult patients with chronic
      rhinosinusitis in Lagos. University Teaching Hospital, Lagos.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) significantly lowers the quality of life
      of patients. The common use of broad spectrum antibiotics for its treatment may
      alter the pathogens that promote the persistence of this condition. However, the
      data concerning the distribution of bacteria species. in patients with CRS are
      not consistent. OBJECTIVE: To isolate the common aerobic and anaerobic bacteria
      from the middle meatal aspirates of adult patients with CRS and determine their
      antibiotic sensitivity patterns Methods: This was a case-control study of adults
      with diagnosis of CRS. Middle meatal aspirate and swab were obtained from cases
      and control respectively for bacteriological studies. Data analysis was done
      using Statistical package for social sciences (SPSS) version 17 Result: Forty one
      aerobic bacteria were cultured. Sixty one percent of the aerobic bacteria
      isolated were gram positive (staphlylococcus.aureus was the most frequently
      found) organisms while the remaining 39% was gram negative. Fifteen peicent of
      the cultured isolates yielded mixed growth of both aerobes (Gram positive and
      gram negative).3(6%) isolates of Bacteroides species were cultured Conclusion:
      The present study found that Staphylococcus aureus, streptococcus pneumoniae,
      Proteus mirabilis, Klebsiella spp, Escherichia coli and Bacteroides spp) were the
      common bacterial flora in the paranasal sinuses of patients with CRS.

PMID- 29465857
TI  - Dental care seeking behaviour of children in a rural Nigerian community.
AB  - BACKGROUND: There is sparse information about oral health seeking behaviour of
      children in rural areas of developing countries. The aim of the Study was to
      determine the dental care seeking-behaviour of children attending the first rural
      based community oral health centre in Nigeria. METHODS: A retrospective review of
      records of patients aged 16 years or younger treated at the Primary Oral Health
      Care Centre in Ibarapa, Nigeria over six years was conducted. Data on
      sociodemographic characteristics of the patients, pattern of presentation and
      their oral hygiene practices were collected and processed using SPSS. RESULTS: A
      total of 239 paediatric patients were seen during the period with a mean age of
      9.7 +/- 4.4 years and 132 (55.2%) were males. The majority, 225 (94.1%), were
      presenting for the first time. All the children sought dental care for one
      problem or the other and the most common reasons for seeking care were: tooth
      ache in 105 (43.9%), trauma in 30 (12.6%) and perceived unclean mouth in 20
      (8.4%) patients. Older children were more likely to seek dental care because of
      pain (p < 0.00 1), while younger children sought care principally on account of
      trauma (p < 0.001) and the under 5 years were seen more often for gum ache (p
      =0.006). The majority, 175 (73.2%), used toothbrush and 182 (76.2%) cleaned their
      teeth once daily. CONCLUSION: None of the children presented for routine check
      up, rather, consultation was as a result of dental problems with toothache being
      the most common reason.

PMID- 29465858
TI  - Perception, attitude and willingness of under-five children caregivers to growth
      monitoring in Ibadan South-West Local Government Area, Oyo State, Nigeria.
AB  - OBJECTIVE: This study was carried out to explore perceptions ofunder five
      caregivers on growth monitoring in Ibadan south-west local government in Nigeria.
      METHOD: Descriptive. cross-sectional-design was used for the study which involved
      four-stage sampling techniques. The study was conducted among the 410 caregivers
      who consented to participate. Both qualitative and quantitative methods were used
      to collect the data. The questionnaire elicited information on sociodemographic
      characteristics, Knowledge, Attitude and Growth -Monitoring perceptions were
      measured on a 16-point scale and categorizedinto "negative" (<=8) and positive
      (>8) Descriptive statistics -using mean and standard deviation were generated
      while qualitative data was analysed using Atlas Ti version 7. Result Mean age of
      the Caregivers of Under-5 was 31.6+/-6.5 years, 46.8% had secondary education and
      56.8% were traders. Majority (88.3%) had received information on Growth
      Monitoring and (66:6%) heard from the health workers. Almost all the: respondents
      (90.0%) had positive perception towards Growth Monitoring (10.8+/-2.9). It was
      also suggested by the caregivers that their involvement is very crucial in
      monitoring the growth of their children. Concusion: The study showed that most of
      the caregivers. had positive perceptions towards growth monitoring and advocated
      their active involvement if training progriammes can be developed.

PMID- 29465859
TI  - Spectrophotometric studies of a novel Gedunin-2-Hydroxypropyl- beta-cyclodextrin
      binary system.
AB  - BACKGROUND: Gedunin, a limonoid, is linked with antimalarial, anticancer and anti
      allergic activities. This study was aimed at preparing an inclusion complex of
      gedunin and 2-hydroxypropyl-p-cyclodextrin (HBD) to increase solubility of
      gedunin in polar solvents which will increase absorption and bioavailability in
      vivo and thus enhance pharmacological effects. MATERIALS AND METHODS: Gedunin was
      obtained from the hexane extract of Entandrophragma angolense heartwood by column
      and preparative thin layer chromatography. The structure was previously confirmed
      by spectroscopic means (NMR). The electronic absorption spectra data of the
      complexes formed between gedunin. and HBD in various solvents was determined
      using the UV-VIS spectrophotometer. The stoichiometry of inclusion was determined
      by Job's method of continuous variation. RESULTS: Evidence of interaction was
      observed between gedunin and HBD in the various solvents but gedunin and its
      complex with HBD exhibited sharp absorption bands in acetate buffer (pH 3.5).The
      spectrophotometric titrations showed curves with a single point of inflexion when
      the experiment was carried'out at 250C (298 K) and 370C (310 K). A stoichiometric
      ratio of 1:1 for complex formation was obtained. The formation constants (K,)
      obtained at 250C and 370C.were 9.539 x.103 M-1 and .1.853 x 104 M-1 respectively.
      Thermodynamic considerations revealed hydrophobic interaction between gedunin and
      HBD. CONCLUSION: A stable inclusion complex of gedunin and HBD was formed at room
      and body temperature. This complex formation involved trapping of poorly soluble
      gedunin into the hydrophobic core of the cyclodextrin and may enhance the
      pharmacological activity of gedunin in vivo.

PMID- 29465860
TI  - Sport participation and injuries among undergraduate students of a Nigerian
      University.
AB  - : Backgroud: Sports participation is a healthy behaviour but it is not without
      the risk of injuries. Information on the extent of sport participation and sport
      injuries among Nigerian Unversity students is sparse. Objeclive: To determine the
      prevalence and types of sport participation and injuries among
      university.students in Nigeria. Factors associated with sport participation among
      students were also examined. METHODS: A cross-sectional survey was conducted
      using a self-administered questionnaire to collect information on the frequcncy
      and types of sport participation and sport-related injuries among a
      representative sample of undergraduate students of the University of Lagos,
      Nigeria. Resuts: A sport participation prevalence of 64.2% (95%CI: 59.5 - 68.7)
      was recorded among students. Football (soccer) (53.2%) had the highest
      participation rate. Male students (78.4% vs.41.2%) participated more frequently
      in sports (p <0.001). Overall injury rate was 52.5 injuries/100 students/ year
      (95%CI: 46.5 - 58.5). The prevalence of injury was 45.7% in male and 12.7% in
      female students. About half (49.3%) of reported injuries resulted in time loss.
      The leg and ankle were the most frequently injured body parts for all injuries
      and most serious injuries. Football recorded the highest prevalence of injury
      (73.8%). CONCLUSION: Sport participation among students was fair and injury rate
      was considerably high, mostly affecting the lower extremity and most injuries
      resulting from football participation. This study suggests the need for improved
      sport participation support among students and the need for the initiation of
      injury prevention initiatives by stakeholders.

PMID- 29465861
TI  - A prospective study of adverse events to antiretroviral therapy in HIV- infected
      adults in Ekiti State, Nigeria.
AB  - OBJECTIVES: Highly active antiretroviral therapy (HAART); the-current standard of
      antiretroviral therapy for Human Immunodeficiency Virus (HIV) infected persons,
      has been documented to drastically, reduce the number of cases of Acquired Immune
      Deficiency Sypdrome (AIDS). However, adverse. events are a challenge to the use
      of HAART. This study intends to determine the nature and incidence of suspected
      advcrse events to prescribed anti retroviral drugs in treatment centers in Ekiti
      State. METHOD: One hundred and twenty participants were enrolled and followed up
      over a period of six months. At each clinic visit, there was an administration of
      a detailed interviewer questionnaire that was completed by the attending
      pharmacist together with the participant. The form is designed to obtain
      information on the demographics of the patients, WHO clinical stage of their HIV
      infection, HAART regimen for the patients, and suspected adverse events
      associated with the antiretroviral drugs used by the patients. RESULTS:
      Tenofovir/Lamivudine/Eifavirenz (72.5%), Zidovudinc/Lamiv.udin/Nevirapine
      (16.7%), Zidovudine/Lamivudiine/ElafIvirenz (6.7%), Tenofovir/
      Lamivudine/Nevirapine (3.3%), and Abacavir/ Lamivudine/Nevirapine (0.8%) were the
      HAART regimens prescribed to the patients. About half (57%) of the participants
      reported clinical adverse events; 92% of which were reported within two weeks of
      HAART initiation. Most of the reported adveise events were nausea (14.5%),
      abdominal discomfort (8.2%), and insomnia (7.5%). A few (6%) of those who
      reported adverse events required regimen switch or drug substitution.
      CONCLUSIONS: Antiretroviral drugs exposure often presents with adverse events, an
      observation similar to other studies. Most of the clinical adverse events were
      not severe or life threatening.

PMID- 29465862
TI  - Validation of a Yoruba version of the arthritis self-efficacy scale.
AB  - BACKGROUND: The Arthritis Self Efficacy Scale (ASES) measures a patient's
      perceived efficacy to cope with the consequences of chronic arthritis. The aim of
      this, study was to translate ASES in to Yoruba, one of the indigenous Nigerian
      languages, and to investigate the validity and reliability of the translated
      version. METHODS: Forty one (21 males; 20 females).patients diagnosed with
      arthritis participated in this cross sectional survey, although only thirty seven
      (87.8%) were available for the reliability study. The ASES was translated to
      Yoruba language using forward-backward translations. Participants completed both
      English and Yoruba version of ASES on the first day while the second
      administration of the two versions of ASES was.. completed at one week after the
      first administrations. Data was analyzed -using descriptive statistics, Spearman
      correlation and intra-class correlation (at p=0.05). RESULTS: There was a
      significant direct correlation (p<0.0001) between the scores obtained on the
      English and Yoruba versions (r=0.933). Also there was a significant direct
      correlation (p<0.0001) between the scores obtained on the first and second
      administrations of the English and Yoruba version of the ASES. CONCLUSION: The
      Yoruba version of the ASES is a valid and reliable outcome measure for health
      outcomes assessment in Yoruba-speaking populations.

PMID- 29465863
TI  - Methods of voluntary reporting medication administration errors among nurses in
      the University College Hospital, Ibadan, Nigeria.
AB  - BACKGROUND: Reporting medication administration error (MAEs) is a significant
      strategy to ensure patient safety. Literature had it that most of what is
      reported as errors of administration is just a tip of the iceberg, suggesting
      that a lot more go unreported. The methods of reporting medication administration
      errors in Nigeria have not been well explored. This study examined the methods of
      reporting MAEs by nurses in selected wards. in the University College Hospital,
      Ibadan. Nigeria. Methods- A cross sectional survey of 286 nurses, who were
      conveniently selected from Medical, Surgical and Accident and Emergency
      departments of the University College Hospital, Ibadan Nurses who gave consent to
      participate completed a 42-item structured questionnaire on the methods and
      reasons for non-reporting MAEs. RESULTS: Among the study cohort, 162(64.8%)
      admitted to have committed MAEs in the past, of which 137(84.4%) voluntarily
      reported. Common methods included reporting to inmmediate supervisor (88; 34%),
      and confiding in a colleague 62 (24.8%). Only 39 (15.6%) documented and completed
      report forms. In addition, 183 (73.2%) believed that anonymous reporting enhances
      the rate of reporting errors. The major reason for non-reporting was the fear of
      being punished and labelled as incompetent practitioner (Mean 3.82, +/- 1.09).
      CONCLUSION: Findings suggest that not all MAEs committed by the study cohort were
      reported, and the methods used differ with individuals and units of practice.
      There is therefore a need to create more awareness that disclosure of MAEs will
      help to identify the specific causes of errors, thereby fostering safe practice.

PMID- 29465864
TI  - Endodontic flare up: incidence and association of possible risk factors.
AB  - BACKGROUND: Endodontic emergency during root canal treatment (flare up) is a
      common occurrence in multivisit root canal treatment (RCT) and it may be
      associated with many factors. The occurrence however can affect the prognosis of
      the tooth and the patient -clinician relationship. AIM: To determine the
      incidence and risk factors associated with occurrence of flare up in a multi
      visit RCT. METHODOLOGY: Patients planned for multi-visit (RCT) were recruited for
      the research. Standard protocol was followed in all cases. After the first visit,
      the patients were followed up for possible development of flare up. Patients'
      demographics, presence or absence of preoperative pain, status of the pulp and
      occurrence of flare up were among the data collected. Data was analyzed using
      SPSS version 20 with level of significance set at P <0.05. RESULT: A total of 106
      root treated teeth were analyzed in patients aged 17 to 73years with a mean of
      33+/-13.2 and male to female ratio of 1:1.5. Incidence of flare up was 8.5%.
      Prior to treatment, 47% of the cases had pain, 61.3% had apical radioluscency and
      83% had pulpal necrosis. Majority (7, 77.8%) of the flare up occurred after the
      first visit (p=0.000). Only pre- treatment pain had a statistical significant
      ielationship with occurrence of flare up (p=0.009). CONCLUSION: Incidence of
      flare up was 8.5% and the major risk factor was preoperative pain. First visit in
      a multi visit RCT is an important stage which if well handled, can reduce the
      incidence of flare up.

PMID- 29465865
TI  - Nicolo Paganini's hair lock for Signora Chatterton - morphological hair
      investigations using digital light microscopy.
AB  - The famous violin virtuoso Nicolo Paganini (born on 27 October 1782 in Genoa,
      died on 27 May 1840 in Nice) left us with many puzzles. An interesting aspect is
      his hair: In the 19th century, hair given away as a token of friendship or
      romantic love became very popular, and Paganini also seems to have made use of
      this fad. In 2009, a lock of hair, purportedly that of Paganini, kept in a locked
      presentation box together with a bilingual autograph inscription saying: "Alla
      Signora Chatterton avec les compliments de Nicolo Paganini" was bought at an
      auction. From this hair lock a sample was taken and was investigated
      morphologically by using digital light microscopy (digital microscope VHX-100,
      Keyence) in reflected and transmitted light with and without polarization at
      different magnifications up to 1:5,000. The sample was then compared with a hair
      sample from the possession of the Paganini family, which had been microscopically
      examined in 2012 by the co-author of this paper yielding numerous figures with
      measurement results that had been stored and could be retrieved for direct
      comparison. The hair sample consisted of ten strands of hair or hair fragments
      and was investigated with great effort for the following parameters: exogenous
      hair damage, especially feeding traces caused by parasites, modeling and
      angulation of hairs, hair thickness, medulla and pigmentation, curling and
      mercury load on the trace material. After evaluation of all findings not only a
      non-exclusion of identity can be determined, but due to the broad match of also
      rare findings there is no reasonable doubt about their identity. In addition, the
      findings suggest that the studied hair samples are in fact from Paganini's head.
      The present case of Nicolo Paganini's hair lock is also an excellent starting
      point for reflections on the probative value of trace hair investigations. This
      point is also critically discussed in the paper. Finally, this study shows that
      said lock of hair had probably really been dedicated and given to Eliza Davenport
      Latham (born on 25 November 1806, died on 9 January 1877), the future wife of
      the, at that time, best-known and most famous English harpist John Balsir
      Chatterton (born on 25 November 1804, died on 9 April 1871). Paganini must have
      met her on his concert tour 1831/32, where he had travelled to Paris, London, the
      rest of England, Scotland and Ireland.

PMID- 29465866
TI  - Field study to detect illicit and medicinal drugs in car drivers in Southern and
      Western Hesse.
AB  - In the present study, immunochemical tests (Mahsan DrugInspector, DOA4, DOA8,
      DOA10, Protzek) as well as the detection rate of police checks were evaluated.
      Urine and blood samples of suspected car drivers were analysed by chromatography
      mass spectrometry. Additionally, anonymised urine samples were analysed on a
      voluntary basis in cases where no legal proceedings were initiated. Toxicological
      analyses (total unknown screening) were performed using gas chromatography-mass
      spectrometry (GC-MS) after hydrolysis, acidic and alkaline extraction and
      derivatization. A data base for screening 9000 substance entries was applied. In
      addition, urine samples were analysed using liquid chromatography/ time-of-flight
      mass spectrometry (HPLC-ToF-MS) to screen psychiatric and narcotic drugs. In
      total, samples of 154 suspects were analysed, of these, 46 samples for no actual
      reason. In 5 of the latter samples, forensically relevant substances were
      detected; in two cases the consumption of illicit drugs, i. e. cannabis and
      methamphetamine, was proved. Of the 154 suspects, 108 were charged with driving
      under the influence of drugs; in samples of 103 of these cases, illicit drugs
      were found. Immunochemical pretesting showed posi- tive results in 97 of the 108
      cases; in 6 samples, psychiatric drugs (citalopram, doxepin, promethazine,
      mirtazapine, fluoxetine, venlafaxine) were later identified, which are not
      detectable by ordinary pretesting systems. Police officers successfully
      identified 95.4 % of the suspects as drug consumers, which is an excellent
      result. In practice, pretesting of urine samples using immunochemical techniques
      proved to be very reliable. The Protzek system in particular corresponded well
      with the results of the chromatographic analyses. In conclusion, systematic
      chromatographic-mass spectrometric analysis of urine samples of suspects is
      recommended to identify car drivers consuming illicit drugs and to obtain data
      usable in legal proceedings (e. g. suspending of the driving license), which is
      not always possible when using blood samples in cases of drugs consumed some time
      ago.

PMID- 29465867
TI  - Lethal hypothermia after firing a suicidal shot to the head in a car.
AB  - In suicide cases involving an automobile, the car is mostly used as a
      tool/instrument for the suicide (intoxication by exhaust fumes, crash against
      solid objects such as a pylon). However, a car is uncommonly also used only as
      the location for a suicide. In the present case, a 70-year-old man had been found
      dead on the passenger seat of his car. According to witnesses, the car had not
      been parked there at the same time of the previous day. During that period, the
      weather had been dry, with temperatures ranging from -10 C at night to +50 C
      during the day. The man had shot himself with a small-caliber revolver (so-called
      bulldog-revolver) almost horizontally in the left temple (transtemporal shot
      through the frontal lobes). Obviously, the suicide had retained the capability to
      act at least for a short time, as the revolver was found under his left bottom.
      As morphological signs of prolonged agony some findings of hypothermia were
      observed (e. g. Wischnewski spots of the stomach).

PMID- 29465868
TI  - Quality of death certificates in hospitals.
AB  - The cause-of-death-statistics and the release of the body for burial depend
      primarily on the information contained in the death certificate. How to handle
      the death certificate has been critically discussed in professional circles again
      and again. A retrospective review of 1,315 deaths from six acute care hospitals
      in Germany was carried out with regard to the quality of the death certificates,
      taking into account information contained in the medical records. The review
      covered the readability of the death certificate, the quality of the epicrisis,
      misclassifications relating to the manner of death and the degree of certainty
      regarding the cause of death. In 93 % of cases (n= 1,221), death certificates
      were clearly legible. In about half the cases (43.3 %, n=569), the quality of the
      entries in the "epicrisis" section was good. In 45 % of cases (n= 592), no
      details were provided in the "epicrisis " section. In 3.9 % (n = 42) of deaths
      classified as natural, information was given indicating a non-natural death. Most
      of these deaths occurred in connection with a fall or an injury (n = 27) or
      possible errors relating to treatment or care (n = 7). Overall, the review showed
      that clinicians handled the medical death certificate in a competent and careful
      manner. However, based on the content of the files, the review identified
      individual and avoidable misclassifications as to the manner of death and
      improbable causes of death; it also demonstrated that information on the
      epicrisis is often missing and needs significant improvement.

PMID- 29465870
TI  - ?

PMID- 29465869
TI  - Unusual planned complex suicide committed with a muzzle-loading pistol in
      combination with subsequent hanging.
AB  - In Germany, suicides by firearms are not very common in contrast to deaths by
      hanging and intoxications. The use of historical muzzle-loading firearms in the
      context of suicides is a rarity. Contact shots from muzzle loaders cause an
      unusual wound morphology with extensive soot soiling. We report the case of a 59
      year-old man, who committed a planned complex suicide by shooting into his mouth
      with a replica percussion gun in combination with hanging. The gunshot injury
      showed strong explosive effects in the oral cavity with fractures of the facial
      bones and the skull associated with cerebral evisceration (so-called Kronlein
      shot). Due to the special constellation of the case with hanging immediately
      after the shot, external bleeding from the head injuries was only moderate.
      Therefore, the head injuries could be assessed and partially reconstructed
      already at the scene.

PMID- 29465871
TI  - [Treatment of hyperkalemia: 2.0 version].
AB  - Hyperkaliaemia is a serious electrolyte disorder that is favored by many
      comorbidities, such as chronic renal failure or some treatments such as renin
      angiotensin-aldosterone system blockers. The new oral treatments by chelation of
      intestinal potassium have demonstrated : 1) their effectiveness in the management
      of serum potassium by maintaining the treatments at optimal dosages ; 2) their
      safety of use by the absence of serious side effect and 3) the ease of use with a
      daily intake.

PMID- 29465872
TI  - [Acid uric : key player in a recently recognized devastating nephropathy and in
      the development of chronic kidney disease.]
AB  - Uric acid has been known since long ago for its implication in gout and in
      certain kinds of nephrolithiasis. However, its role in models of acute and
      chronic nephropathies has been the focus of many new developments. The so called
      Mesoamerican nephropathy is a devastating disease that has caused more than
      20'000 deaths in central America these last few years among sugarcane workers.
      Acid uric could play a key role in its physiopathology. Moreover, acid uric tends
      to be recognized as an independent factor of development and progression in
      chronic kidney disease, opening a way for new therapeutic targets.

PMID- 29465873
TI  - [What place for therapeutic education in nephrology ?]
AB  - Chronic kidney disease (CKD) usually goes unrecognized for patients until late
      symptomatic stages. In preterminal CKD, extrarenal substitution methods are
      usually presented to patients. This is felt like a breakdown, implying major
      modifications of everyday life. Acquisition of health literacy is necessary for
      patients with CKD to become autonomous and increase their empowerment toward the
      disease. Therapeutic education in nephrology plays a major role in improving the
      care of CKD patients.

PMID- 29465874
TI  - [Gut microbiota and kidney diseases : dangerous liaisons?]
AB  - Recent studies have found a relationship between the kidney and the intestinal
      microbiome, called the colo-renal axis. Mounting evidence suggests that patients
      suffering from chronic kidney disease (CKD) have an altered composition of gut
      microbiota. This leads to 1) the increased fermentation of intestinal proteins to
      uremic toxins such as p-cresyl sulphate and indoxyl sulphate, 2) an altered, more
      'leaky' intestinal barrier, and 3) translocation of bacteria and toxins from the
      gut lumen to the circulation, inducing systemic inflammation. This may contribute
      to the increased morbidity and mortality in this population. Future studies are
      needed to confirm this hypothesis, and to assess whether manipulating the
      intestinal microbiota with pre-, pro-, or symbiotics may alter the development
      and course of CKD.

PMID- 29465875
TI  - [Calcific uremic arteriolopathy (calciphylaxis)  : update in 2018].
AB  - Calciphylaxis is a rare disease with a poor prognostic that mostly occurs in
      patients with renal failure. Diagnosis is difficult and skin biopsy is the gold
      standard diagnostic procedure, although it may aggravate skin lesions.
      Identification of the typical cutaneous signs is important to initiate adequate
      medical care. Several differential diagnoses must be excluded. Treatments should
      include appropriate pain management, local wound pain, daily dialysis,
      intravenous sodium thiosulfate treatment, hyperbaric oxygenotherapy, thigh
      control of calcium-phosphate metabolism and interruption of medications that
      could contribute to calciphylaxis. Palliative care should be considered in
      uncontrolled clinical course.

PMID- 29465877
TI  - ?

PMID- 29465876
TI  - [Return to dialysis after kidney transplantation: a retrospective study in the
      Canton de Vaud].
AB  - Renal transplantation is the first-line therapy for eligible patients with end
      stage kidney disease. However, approximately 20 % of cadaveric graft recipients
      need to start dialysis at 5 years. The transition period between transplantation
      and dialysis is at high risk of complications, but data exploring this issue are
      scarce. In this retrospective study from dialysis centres of the Canton de Vaud,
      we analysed the clinical data and management of these patients at the beginning
      of dialysis after graft loss, and up to one year after dialysis start. Our data
      show that such patients suffer from a high rate of complications, such as urgent
      start of dialysis, hospitalizations, severe hypertension and depression. We
      suggest that clinical management in this period should be revisited.

PMID- 29465878
TI  - ?

PMID- 29465879
TI  - ?

PMID- 29465880
TI  - ?

PMID- 29465881
TI  - ?

PMID- 29465882
TI  - ?

PMID- 29465883
TI  - ?

PMID- 29465884
TI  - ?

PMID- 29465885
TI  - [Meningioma and pregnancy].
AB  - Meningiomas are one of the most frequent primary intracranial tumours,
      representing one-third of all intracranialneoplasms. The vast majority of
      meningiomas are histologically benign, but recurrence and progression is quite
      frequent. They occur usually between the 6th and 7th decade, the female/male
      ratio is 3:2. Although rare in pregnancy, when occurring, they can cause serious,
      life-threatening complications due to rapid growth and unfavourable localisation.
      There are two dominant hypothesis explaining rapid growth in pregnancy: the role
      of hormonal effects and hemodynamic changes. Several studies tested these
      theories but none provided unequivocal answer probably because the pathomechanism
      is complex and multifactorial. We provide an overview of the pathomechanism of
      meningiomas in pregnancy with emphasis on data obtained by advanced
      neuropathological, molecular biological, bioinformatic, imaging and
      epidemiological methods. A better understanding of the processes leading to
      meningioma development and growth in pregnancy will help us to design
      personalized therapy and reduce morbidity and mortality.

PMID- 29465886
TI  - Syndrome of trephined-underestimated and poorly understood complication after
      decompressive craniectomy.
AB  - Decompressive craniectomy (DC) is still a matter of debate, with a numerous
      complications as expansion of haemorrhagic contusions, external cerebral
      herniation, subdural hygromas, post-traumatic hydrocephalus (HC). The often
      overlooked "syndrome of the trephined" (ST) as a delayed complication of DC also
      known as sinking skin flap sy initially described in 1939.ST is characterised by
      the neurological changes associated with alteration of the pressure/volume
      relationship between intracranial pressure (ICP), volume of cerebrospinal fluid
      (CSF), blood, and brain tissue in patients with large bone defects. This review
      aims at elucidating the mechanisms responsible for the development of ST, and
      providing useful tips and red-flag signs for healthcare professionals involved
      with care of post DC patients. Symptoms identified on time could help to develop
      appropriate treatment strategies for this suddenly deteriorating, but possible
      reversible condition. Although the treatment strategy is straightforward, calling
      for a prompt cranioplasty, the correction of HC through CSF diversion devices
      might require a lengthy optimisation period. Continuous changes in the setting of
      the shunting systems or spinal tap might lead to dangerous swinging of the
      midline structures causing further neurological deterioration. Thus, finding the
      right balance in terms of clinical management often represents a significant
      challenge.

PMID- 29465887
TI  - [The role of zonisamide in the management of pediatric partial epilepsy].
AB  - In our review we discuss the group of approved antiepileptic drugs for children
      in Hungary. We cite the results of the review conducted by the International
      League Against Epilepsy on antiepileptic drug efficacy and effectiveness as
      initial monotherapy for newly diagnosed epileptic seizures and syndromes in
      pediatric age group. 25% of pediatric epilepsy is therapy resistant, so we
      further need new drugs, which must be investigated according to the rules of the
      European Medicine Agency. The ethical dilemmas of childhood drug studies lead to
      the situation that the new antiepileptic drugs, approved as monotherapy in adult
      epilepsies, are in the majority just in add-on regimen tested in pediatric
      patients. As clinicians we appreciate open label extension safety studies. An old
      new antiepileptic drug in Europe is zonisamide. Though it was approved for first
      line monotherapy in pediatric and adult patients with partial and generalised
      epilepsy in 1989 in Japan, the European Medicine Agency licensed its use as
      adjunctive therapy in children aged 6 years or older with partial seizures (with
      or without secondary generalisation) just in 2013. The results of the openlabel
      extension study appeared in 2014. The mean dose received was 7.5 mg/kg/day.
      During the open label phase 11% of the patients achieved seizure freedom and it
      was maintained throughout the study. The drug was generally well tolerated. The
      most frequently reported treatment-related adverse events were decreased weight
      (6%), decreased appetite (4%), and headache (2%). No new or unexpected side
      effects emerged. In conclusion oral zonisamide as adjunctive therapy in pediatric
      patients aged 6-17 years with partial seizures demonstrated an acceptable safety
      and tolerability profile and efficacy over a period at least 1 year. So it is a
      good treatment option in this population.

PMID- 29465888
TI  - [Angioneuritic edema in ischaemic stroke patients treated with rt-PA].
AB  - Data of our 254 patients who were treated with rt-PA between 1st of Jan, 2011 and
      31st of Dec, 2014 were processed. We focused on angioneurotic oedema as allergic
      complication of thrombolysis which caused life threatening respiratory
      obstruction in two cases. We describe these two patients' history. Out of 254
      patients six (2.3%) suffered angioneurotic edema caused respiratory obstruction
      in two (0.90%) cases. This occurrence is approximately 1.3-5.1% in literature.
      Five, out of six patients who suffered from angioneurotic oedema, had been
      treated with ACE inhibitors or ARB before. The role of ACE inhibitors is known in
      metabolism of bradykinin cascade. Plasmin which present during thrombolysis,
      precipitates biochemical mechanisms of this potential life threatening
      complication. Therefore rt-PA alone can be the cause of angioedema, but it can be
      more frequent together with ACE inhibitors therapy.

PMID- 29465889
TI  - [Transthyretin familial amyloid polyneuropathy - three Hungarian cases with rare
      mutations (His88Arg and Phe33Leu)].
AB  - Introduction - Transthyretin familial amyloid polyneuropathy is a rare autosomal
      dominant progressive systemic disesase of adults caused by endoneural amyloid
      deposition due to point mutations of the transthyretin gene. It is the most
      severe form among hereditary polyneuropathies, being fatal within 10 years if
      left untreated. The disease is underdiagnosed, the late onset forms (above the
      age of 50) being probably more widespread than previously thought. Early
      diagnosis is essential as the early introduction of causal therapy (tafamidis)
      slows progression and prolongs survival. Patients - We report here three non
      related Hungarian cases of transthyretin familial amyloid polyneuropathy with non
      Val30Met mutations (His88Arg in two cases, Phe33Leu in one case). They were all
      characterized by late-onset, progressive, length-dependent, axonal, sensorimotor
      polyneuropathy and the simultaneous presentation of severe restrictive
      cardiomyopathy. In all three cases, clinical and electrophysiological signs of
      myopathy were also present, suggesting the involvement of skeletal muscles as
      well. In two cases, high resolution ultrasound of the peripheral nerves was also
      performed, which showed segmental structural alterations (change or loss of
      fascicular structure) and some increase of echogenicity of the interfascicular
      epineurium, without substantial enlargement of the nerves. Conclusion - In
      Hungary, mainly the rare, non-Val30Met mutation forms of transthyretin familial
      amyloid polyneuropathy are encountered, as in our cases. As opposed to the
      Val30Met forms, these mutations are characterized by late onset and simultaneous
      presentation of severe cardiomyopathy. Our report highlights the importance of
      considering transthyretin familial amyloid polyneuropathy in the differential
      diagnosis of late-onset, progressive, axonal polyneuropathies of unknown
      etiology, particularly if associated with cardiac disease.

PMID- 29465890
TI  - [The effect of anesthesia on cognitive functions].
AB  - Aim of the study - General anesthetics, arterial hypotension and hypoxia
      developing during anesthesia may result in impaired memory and a decline in other
      abilities (such as attention, concentration, linguistic and writing abilities).
      Our aim was to detect changes in cognitive functions due to surgery and
      anesthesia with controlled arterial hypotension. Materials and methods - We
      studied combined and intravenous anesthesia detecting pre-and postoperative
      cognitive functions, intraoperative haemodynamic parameters, demographic data,
      other data of case history and surgical data. The Montreal Cognitive Assessment
      test was applied in the randomized, prospective study. The preoperative data
      served as basis for comparison. The second test was performed following surgery
      when patients were fully awake. Both groups included 30 patients. Results and
      conclusion - After both narcosis methods (postoperative second hour) cognitive
      functions were significantly deteriorated (p<0.05). Median MoCA before
      sevoflurane anesthesia was 24 points (interquartile range: 22-25), postoperative
      value was 20 (19-21) (p<0.05). Median MoCA before propofol anesthesia was 24
      points (23-26), postoperative value was 20 (18-22) (p<0.01). Intraoperative
      arterial blood pressure, pulse rate and oxygen saturation values did not
      correlate with worsening of cognitive function (Pearson correlation coefficient
      values between -0.19 and 0.42). Execution is influenced by age (negative
      correlation) and education (positive correlation).

PMID- 29465891
TI  - Gray matter atrophy in presymptomatic Huntington's patients.
AB  - Background and purpose: Background - Huntington's disease is a progressive
      disease in which neurodegeneration is on-going from the early presymptomatic
      phase. Development of sensitive biomarkers in this presymptomatic stage that are
      able to monitor the disease progression and test the efficacy of putative
      neuroprotective treatments are essential. Methods: Methods - Seven presymptomatic
      Huntington mutation carriers and ten age-matched healthy controls were recruited.
      Six of the patients participated in a 24 months longitudinal study having MRI
      scans 12 and 24 months after the baseline measurements. High resolution T1
      weighted images were carried out and voxel based morphometry was used to analyse
      the data. Apart of group differences, correlation of CAG repeat number with focal
      cortical thickness and with global gray matter volume was calculated. Results:
      Results - Focal cortical atrophy was found bilaterally in the superior temporal
      sulcus and in the left middle frontal gyrus in presymptomatic Huntington patients
      in whom no sign of cognitive or motor deterioration was detected. Global gray
      matter atrophy (p<0.048) and decreased total brain volume was found. The number
      of CAG triplets showed no correlation with the focal gray matter atrophy and
      total brain volume. Strong correlation between the CAG repeat number and global
      gray matter volume was found (p<0.016). Conclusion: Conclusion - Cortical atrophy
      is apparent in the early, presymptomatic stage of the disease. With further
      validation in large patient sample atrophy measure could be biomarker of disease
      progression and putatively of neurodegeneration.

PMID- 29465892
TI  - Burning mouth syndrome: Evaluation of clinical and laboratory findings.
AB  - Background and purpose: Burning mouth syndrome is a chronic and persistent
      painful condition characterized by burning sensation in the oral mucosa. We
      investigated the etiological factors of patients presented with the history of
      burning in the mouth who admitted our outpatient clinics over the 8-years period
      and who had no underlying identifiable local factors. We also tried to determine
      their demographic and clinical characteristics. Our aim was to investigate the
      association between burning mouth and psychiatric disorders such as depression
      and anxiety, chronic diseases like diabetes mellitus (DM) and other laboratory
      studies in patients complaining of solely burning in the mouth. Methods: The
      study included patients with the history of burning in mouth who presented in our
      outpatient clinic between 2005 and 2012. They were evaluated by a neurologist, a
      psychiatrist, an internist, and a dentist. Complete blood counts, biochemical
      analysis and cranial magnetic resonance imaging (MRI) were performed for all
      patients. Results: A total of 26 (22 (84%) females, 4 (15%) males; mean age 55.9
      years) patients were enrolled in this study. Five (19.2%) of the patients had
      depression, 2 (7.7%) had anxiety disorder, 2 (7.7%) had diabetes mellitus, 8
      (30%) had B12 vitamin deficiency, 3 (11.5%) had decreased ferritin levels in
      blood, and 1 (3.8%) had folic acid deficiency. Cranial MRI of all patients were
      normal. Nine patients (34.6%) had no etiological causes. Conclusion: A
      multidisciplinary approach in the management of burning mouth and establishment
      of common criteria for the diagnosis would provide insight into the underlying
      pathophysiological mechanism.

PMID- 29465893
TI  - Association of anterior thoracic meningocele and azygos lobe of the lung.
AB  - Here we report an anterior thoracic meningocele case. Twoyears- old female
      patient was presented with kyphosis. Azygos lobe of the lung was also
      demonstrated during radiological studies. Posterolateral thoracotomy incision and
      extralpeural approach was performed for excision of the anterior meningocele to
      untether the cord. Although both anomalies are related to faulty embryogenesis
      and it is well known that faulty embryogenesis may also reveal coexisting
      abnormalities, we could not speculate a common mechanism for anterior thoracic
      meningocele and azygos lobe of the lung association.

PMID- 29465894
TI  - Four cases of GABAB receptor encephalitis.
AB  - GABAB receptor (gamma-aminobutyric acid type B receptors - GABABR) encephalitis
      is a rare manifestation of autoimmune encephalitides. We report four cases -
      including the first two Hungarian patients - with some peculiar features. One
      patient developed subacute disorientation and almost complete loss of short-term
      memory, but no epilepsy. Without immunotherapy, his memory spontaneously improved
      up to mild cognitive impairment in six weeks. GABABR antibodies persisted in his
      serum, and 18 months later, FDG-PET detected abnormal mediastinal lymph nodes and
      small cell lung cancer (SCLC). Another patient had persistently decreased sodium
      content in the peripheral blood. In those three patients who died, CSF was
      abnormal, but CSF was not pathological in the patient, who spontaneously
      improved. Brain MRI indicated signal intensity changes in the medial temporal
      areas in three cases. SCLC was found in three patients. Only the patient, who
      spontaneously improved, survived for more than 24 months. In summary, our cases
      show that (i) GABABR encephalitis may develop without epilepsy; (ii) the severe
      short-term memory loss can spontaneously improve; (iii) persistent hyponatremia
      can be present in the blood; (iv) the patient with benign course without epilepsy
      and CSF abnormality survived; (v) spontaneously remitting encephalitis can
      precede SCLC by 1.5 year, which emphasizes that repeated search for cancer is of
      paramount importance even in cases with spontaneous improvement.

PMID- 29465895
TI  - [Clinical neurophysiological methods in diagnosis and treatment of
      cerebrovascular diseases].
AB  - Neurophysiological methods are gaining ground in the diagnosis and therapy of
      cerebrovascular disease. While the role of the EEG (electroencephalography) in
      the diagnosis of post-stroke epilepsy is constant, quantitative EEG para-meters,
      as new indicators of early efficiency after thrombolysis or in prognosis of
      patient's condition have proved their effectiveness in several clinical studies.
      In intensive care units, continuous EEG monitoring of critically ill patients
      became part of neurointenzive care protocols. SSEP (somatosesnsory evoked
      potencial) and EEG performed during carotid endarterectomy, are early indicative
      intraoperativ neuromonitoring methods of poor outcome. Neurorehabilitation is a
      newly discovered area of neurophysiology. Clinical studies have demonstrated the
      effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the
      rehabilitation of stroke patients. Brain computer interface mark the onset of
      modern rehabi-litation, where the function deficit is replaced by robotic
      tehnology.

PMID- 29465896
TI  - Insights into the structure and function of the hippocampal formation: Relevance
      to Parkinson's disease.
AB  - The link between the hippocampus and declarative memory dysfunctions following
      the removal of the medial temporal lobe opened unexplored fields in neuroscience.
      In the first part of our review, we summarized current theoretical frameworks
      discussing the role of hippocampus in learning and memory. Several theories are
      highlighted suggesting that the hippocampus is responsible for assembling
      stimulus elements into a unitary representation that later can be utilized to
      simulate future events. The hippocampal formation has been implicated in a
      growing number of disorders, from neurodegenerative diseases to atypical
      cognitive ageing and depression. Recent neuroimaging studies provided new
      opportunities to study in detail the hippocampal formation's role in higher
      levels of the nervous system. We will present data regarding the regional
      specialization of the hippocampus in experimental models developed for healthy
      and neurological conditions with a special focus on Parkinson's disease. Combined
      evidence from neuroimaging studies suggested that hippocampal volume is reduced
      in non-demented, newly diagnosed patients with Parkinson's disease, which is
      associated with impaired memory performance. These findings proposed that, beyond
      the well-known striatal dopamine loss, impaired hippocampal synaptic plasticity
      may contribute to cognitive and affective impairments in early Parkinson's
      disease.

PMID- 29465897
TI  - [Effects of nasal provocation with a single-dose allergen on the explicit and
      implicit memory of physically active and inactive patients with ragweed allergy].
AB  - Background and purpose: Allergy is an endemic disease and has a considerable
      impact on the quality of life. This study aimed to measure the effect of active
      allergic rhinitis on memory functions of physically active and inactive patients
      with ragweed allergy. Methods: Memory functions were assessed before and after
      allergen exposure. Participants in both groups were provoked nasally with 30
      IR/mL ragweed allergen in each nostril. Explicit memory was measured with story
      recalling and implicit memory was investigated with reaction time task. Results:
      In neuropsychological assessments athletes performed significantly better,
      compared with the control group after allergen provocation in short-term and long
      term memory functions. There was no difference between the groups in the implicit
      tasks. Athletes have achieved better results after provocation, comparing to the
      baseline test and the tests that measured short-term and long-term memory
      functions. Conclusion: Short-term disturbing factors, e.g. swollen nasal mucosa,
      sneezing, and watery eyes after provocation did have not caused deterioration in
      cognitive functions. A single-shot allergen in high doses have caused an increase
      of mental concentration, which was more pronounced in athletes.

PMID- 29465898
TI  - Functional neurotoxicity and tissue metal levels in rats exposed subacutely to
      titanium dioxide nanoparticles via the airways.
AB  - Background and purpose: Nanoparticles of titanium dioxide are suspected
      neurotoxic agents and have numerous applications possibly resulting in human
      exposure by several ways including inhalation. In the present work, rats were
      exposed to spherical TiO2 nanoparticles of two different sizes by the
      intratracheal route. It was investigated how the neuro-functional alterations,
      detected by electrophysiological and behavioral methods, were related to the
      concentration of Ti in the tissue samples and what the influence of the size of
      the NPs was. Methods: Rats (young adult Wistar males, 10/group) were exposed to
      TiO2 nanoparticles of ca. 10 and 100 nm diameter (suspension medium: neutral PBS
      with 1% hydroxyethyl cellulose) by intratracheal instillation in 5 and 18 mg/kg
      b.w. dose; 5 days per week for 6 weeks. Controls were instilled with saline, and
      vehicle controls, with the suspension medium. To see general toxicity, body
      weight was checked daily, and organ weights were measured at the end of
      experiment. Grip strength test, to assess motor function damage, was done before
      and after the 6-week treatment. Finally, the rats were anesthetized with
      urethane, spontaneous cortical activity and sensory evoked potentials were
      recorded, then the rats were dissected and tissue samples were taken for Ti level
      measurement. Results: Body weight gain indicated no general toxicity, and no
      significant change in the relative organ weights, except that of the lungs, was
      seen. However, change of time-to-fall in the grip strength test, and latency of
      cortical evoked po-tentials, were altered in the treated groups, indicating
      functional damage. Correlation of these alterations with the cortical Ti level
      was dissimilar for the two sizes of nanoparticles. Conclusion: The results
      provided further support to the functional neurotoxicity of TiO2 nanoparticles.
      The exact role of particle size, and the mechanisms involved, remain to be
      elucidated.

PMID- 29465899
TI  - Electroclinical and prognostic characteristics of epilepsy patients with
      photosensitivity.
AB  - Background and purpose: Epilepsy with photosensitivity (PSE) is one of the reflex
      epilepsy types with pathophysiology still unexplained. In our study we aimed to
      evaluate the clinical, electroencephalogram (EEG) and prognosis of patients with
      PSE diagnosis. Methods: A total of 44 patients with PSE diagnosis according to
      international classification were included in this retrospective and cross
      sectional study. The age, gender, syndrome, clinical and EEG characteristics of
      patients, and treatment response were investigated. Results: The mean age was
      22.09+/-6.49 years for 28 females and 16 males included in the study. Of
      patients, 17 had idiopathic photosensitive occipital lobe epilepsy (IPOLE), 11
      had juvenile myoclonic epilepsy (JME), 11 had other PSE and 5 had juvenile
      absence epilepsy (JAE), with the most common visual trigger factors television
      and sunlight. In terms of seizure type, the most common was generalized tonic
      clonic seizure (GTCS), with myoclonus, absence and other seizure types observed.
      There was family history present in 17 patients and valproic acid was most
      commonly used for treatment. Conclusion: As noted in the literature, our data
      show that PSE has defined age group and clinical presentation, good prognosis but
      requires correct choice of medication for treatment. It is thought that good
      description of these epilepsy types will reduce misdiagnosis and mistreatment
      rates.

PMID- 29465900
TI  - Alteration of mean platelet volume in the pathogenesis of acute ischemic stroke:
      cause or consequence?
AB  - Background and purpose: Platelets have a crucial role on vascular disease which
      are involved in pathogenesis of ischemic stroke. Platelet size is measured as
      mean platelet volume (MPV) and is a marker of platelet activity. Platelets
      contain more dense granules as the size increases and produce more serotonin and
      tromboglobulin (b-TG) than small platelets. In this study, the alteration of MPV
      values were investigated in patients with acute stroke, who had MPV values before
      stroke, during acute ischemic stroke and 7 days after the stroke. The
      relationship between this alteration and risk factors, etiology and localization
      of ischemic stroke were also investigated. Methods: Sixty-seven patients with
      clinically and radiologically established diagnoses of ischemic stroke were
      enrolled into the study and stroke etiology was classified by modified Trial of
      Org 10 172 in Acute Stroke Treatment (TOAST) classification and, modified Bamford
      classification was used for localization and stroke risk factors were also
      evaluated. The platelet counts and MPV values from patient files in patients who
      had values before stroke (at examination for another diseases), within 24 hours
      of symptom onset and after 7 further days were analysed. Results: MPV values
      increased after stroke (10.59+/-2.26) compared with acute stroke values (9.84+/
      1.64) and the values before stroke (9.59+/-1.72) (p<0.0001); this alteration of
      MPV values occured 7 days after stroke (p<0.016). There was a positive
      correlation between age and MPV values during acute stroke (r=0.270; p<0.05).
      Patients with atrial fibrillation had higher alteration in the time of MPV
      compared with patients without atrial fibrillation (p>0.006). We assessed for
      gender, men (n=38) had a higher alteration in the time of MPV compared with women
      (n=29) (p=0.013). Conclusion: Although there was no alteration of platelet
      counts, MPV values were increased 7 days after stroke in patients with acute
      ischemic stroke.

PMID- 29465901
TI  - Association of cardiovascular risk factors and Parkinson's disease - case-control
      study in South East Hungary.
AB  - Background and purpose: Parkinson's disease (PD) has the second highest incidence
      among neurodegenerative diseases in the world population. The study aimed to
      investigate the presence of some cardiovascular risk factors - dyslipidemia,
      diabetes, and hypertension - in PD patients and to compare their risk with non-PD
      population in South East Hungary. Methods: A case-control study was conducted at
      the Department of Neurology, University of Szeged, Hungary. The study included
      1299 subjects out of which 620 patients were identified as cases of diagnosed PD
      and 679 as controls. Logistic regression analyses were conducted to reveal the
      association of vascular risk factors with PD. Results: In the univariate
      analysis, diabetes mellitus was positively associated with PD, while dyslipidemia
      showed negative association to it in the total population, and no significant
      associations were found between hypertension and PD. The multivariate logistic
      regression models showed that the odds of diabetes mellitus was higher (OR=2.86),
      while the odds of dyslipidemia was lower (OR=0.58) among PD patients than in the
      control group. Hypertension showed a different pattern by gender: the odds of
      registered hypertension was significantly lower in female PD patients (OR=0.68),
      whereas the result was not significant in males. Conclusion: This is the first
      study that provides a comprehensive view of the cardiovascular risk factors in PD
      patients in Hungary and shows considerable relationship between diabetes mellitus
      and PD.

PMID- 29465902
TI  - [The facets of creativity in the light of bipolar mood alterations].
AB  - The link between creativity, as the highest expression form of human achievement,
      and bipolar disorder came into focus of scientific investigations and research.
      Accomplished writers, composers and visual artists show a substantially higher
      rate of affective disorders, prodominantly bipolar mood disorders, comparing to
      the general population. Then again, patients afflicted with bipolar II subtype
      (hypomania and depression), as well as persons presenting the mildest form of
      bipolar mood swings (cyclothymia) possess higher creative skills. It evokes
      therefore that certain forms and mood states of bipolar disorder, notably
      hypomania might convey cognitive, emotional/affective, and motivational benefits
      to creativity. The aim of this paper is to display expression forms of creativity
      (writing, visual art, scientific work) as well as productivity (literary and
      scientific work output, number of artworks and exhibitions, awards) in the light
      of clinically diagnosed mood states at an eminent creative individual, treated
      for bipolar II disorder. Analysing the affective states, we found a striking
      relation between hypomanic episodes and visual artistic creativity and
      achievement, as well as scientific performance, whereas mild-moderate depressed
      mood promoted literary work. Severe depression and mixed states were not
      associated with creative activities, and intriguingly, long-term stabilised
      euthymic mood, exempted from marked affective lability, is disadvantageous
      regarding creativity. It seems, thereby, that mood functions as a sluice of
      creativity. Nevertheless, it is likely that there is a complex interaction
      between bipolar mood disorder spectrum and psychological factors promoting
      creativity, influenced also by individual variability due to medication, comorbid
      conditions, and course of disorder.

PMID- 29465903
TI  - Population structure and reproduction of a migratory fish Leporinus piau
      (Characiformes: Anostomidae) in a semiarid tropical reservoir, Brazil.
AB  - Migratory fishes have been seriously impacted by the building of reservoirs and
      because of the negative effects of these projects such as the interruption of
      migratory routes, reduction or elimination of spawning/feeding areas, and initial
      development can influence the population structure the migratory fishes,
      resulting in reduction in abundance. Leporinus piau is migratory fish widely
      distributed in the watersheds of the Brazilian semiarid and it is of importance
      for artisanal and sport fishing. The goal of the study was to evaluate the
      population structure and reproductive dynamics of the migratory species Leporinus
      piau in the Pau dos Ferros Reservoir, which is located in the semiarid region of
      Brazil. The CPUE, length structure, length-weight relationship, length at first
      maturity, sex ratio, gonad development and IGS were analyzed. Collections were
      performed quarterly between February 2011 and November 2012 using gillnets. The
      captured fish were counted; the standard length (cm) and total weight (g) were
      measured, and dissected to determine the sex and gonad maturity stage. The
      rainfall and reservoir water levels were recorded, and their correlations with
      the reproductive period and CPUE were analyzed. A total 549 individuals were
      captured. The average CPUE varied between 0.0259 individuals/m2*h (May/2011) and
      0.0008 individuals/m2*h (August/2012), and significant differences were observed;
      however, significant correlations were not observed between rainfall and
      reservoir levels. The standard length varied between 5.9 cm and 20.7 cm, and the
      weight varied between 4.16 g and 271.5 g. A histogram analysis revealed that the
      5-10 cm standard length class was the most abundant for juveniles and that the 10
      15 cm class was the most abundant for adult females and males. The weight-length
      relationship was best fit by the equation log10Wt = -1.57711 + 3.00707 Log10 Ls,
      and the species presented isometric growth. The estimated length at first
      maturity was 12.76 cm. A total of 148 males and 82 females were collected
      (1.81:1, M:F), and these values were significantly different. The highest GSI was
      observed in February 2011 for both females (10.69) and males (5.72), and the GSI
      was significantly and positively correlated with rainfall. We concluded that the
      L. piau population is established in the reservoir and found that its
      reproduction period occurred during the rainy season between February and May.

PMID- 29465904
TI  - Effect of a major highway on the spatial and temporal variation in the structure
      and diversity of the avifauna of a tropical premontane rain forest.
AB  - Roads immersed in conservation areas will increase in number, size, and traffic
      over the next decade, and thus, understanding their effects on forest-dependent
      wildlife is crucial for improving current management practices and reducing the
      negative impacts of roads on sensitive species. We examined the influence of
      route 32 (a.k.a. Guapiles Highway) on temporal and spatial changes in the
      structure of the avifauna of Braulio Carrillo National Park, Costa Rica, a site
      crossed by this road along 25 km. The highway connects the capital city of San
      Jose with the Harbor of Limon in the Caribbean Sea (142 km). Although the road is
      narrow (12 m in width and comprised by two lanes along most of the route) it
      services over 1.5 million motor vehicles per year, 12 % are heavy trucks and
      trailers. We expected the highway to divide the avifauna, and thus to observe
      significant differences in species structure on opposite sides of the road. We
      described changes in bird diversity between wet and dry seasons at Las Palmas and
      Ceibo trails located on opposite sides of the highway (14 point counts per
      trail), and evaluated how abundance and diversity varied with road distance.
      Censuses took place during wet and dry seasons from 2002 to 2005. We listed 245
      species and 6 035 observations during the 4-yr survey. Rare species dominated the
      avifauna (65 % of species < 5 observations), and species overlap between trails
      was high (Sorensen= 71 %; Morisita= 0.96). Species accumulation curves varied
      little among trails, yielding 190 species. Resident species represented 70 % of
      observations, followed by elevational (15 %) and long-distance migrants (1-2 %).
      Understory species were the most abundant (60 %) followed by canopy birds (30 %).
      Species turnover rate was 55 % between seasons, but species composition between
      trails remained homogeneous. Overall, birds were avoiding the road (abundance
      increased away from the road) although other diversity parameters (richness,
      dominance, Shannon index, and equitability) were not influenced by road
      proximity. Although the avifauna remained homogeneous on both sides of the road,
      which did not support the fragmentation hypothesis, the highway reduced the
      abundance and diversity of specialized understory insectivores associated with
      primary forests near the road. This highway will expand outside the National Park
      (from 2 to 4 lanes along 107 km from Rio Frio to Limon) in the next years, which
      will increase traffic volume and road impacts within the Park. Roads are
      increasing across highly diverse tropical areas justifying the need for
      management practices based on the identification of sensitive groups.

PMID- 29465905
TI  - The geographic distribution of Costa Rican velvet worms (Onychophora:
      Peripatidae).
AB  - Velvet worms, "peripatus" or onychophorans, are "living fossils" that were
      geographically widespread in Cambrian seas but now occur exclusively on
      terrestrial habitats. The only extant species studied in some detail are those
      from Costa Rica, but their real geographic distribution was in urgent need of
      revision. To solve this problem we visited the localities mentioned in all the
      original taxonomic descriptions and redescriptions. These visits covered a 25
      year period (1988-2014) and included interviews with local residents. We also
      examined all Costa Rican collections, and checked the information in old maps and
      books. Here we critically review geographic data, correct errors, designed
      neotype localities, report on the survival of populations after heavy volcanic
      eruptions or urbanization, and present the correct geographical distribution for
      the seven currently described Costa Rican species.

PMID- 29465906
TI  - [Population ecology of Heteromys pictus (Rodentia: Heteromyidae), in a tropical
      deciduous forest with human disturbance, in Oaxaca coast, Mexico].
AB  - Spiny pocket mice Liomys and Heteromys are forest-dwelling granivorous rodents
      distributed in seasonally dry forest or thorn scrub along the Pacific lowlands or
      xeric regions in the Mexican Plateau. We analyzed the population dynamics of the
      spiny pocket mouse Heteromys pictus, in the coast of Oaxaca, Mexico, in two sites
      of tropical deciduous forest with different degrees of disturbance: ZPP = less
      disturbed site, and ZMP = more disturbed site. Two plots were established in each
      area with 66 trap stations; we used the capture-recapture method and trapping for
      12 periods for one year. Population density was estimated using the method of
      Minimum Number of Individuals Known Alive (MNKA). We captured 706 individuals,
      290 for the ZPP and 416 for the ZMP. The population density ranged from 28 to 142
      ind./ha for both zones, but it was higher for the ZMP (54 against 142 ind./ha).
      The population density for both areas increased during the rainy season and
      coincided with the increased recruitment of adults. Reproductive activity
      occurred throughout the study period in both areas, but it was higher for the
      ZMP. The sex ratio in the ZPP was 1:1 while in the ZMP was 1:0.75. In the ZMP we
      found a higher population density and reproductive activity in females, compared
      to the ZPP. These results suggest that H. pictus prefers the ZMP, indicating that
      thespeciesisnot significantly affected by human disturbance in the studied
      location.

PMID- 29465907
TI  - In vitro antioxidant activity and qualitative phytochemical analysis of two
      Vismia (Hypericaceae) species collected in Los Andes, Venezuela.
AB  - Vismia genus is distributed mainly in tropical and subtropical regions of
      Central, South America and some areas of Africa. According to previous
      investigations, antioxidant potential of Vismia species might be related to
      anthrones, anthraquinones, flavonoids and phenol derivatives biosynthesized by
      these plants. In this investigation, phytochemical screening of Vismia baccifera
      (VB) from Merida-Venezuela and Vismia macrophylla (VM) from Tachira-Venezuela
      methanolic extracts, carried out using various chemical assays, revealed an
      abundant presence of anthraquinones in both species analyzed. Glycosides were
      also present while flavones and dehydroflavones were observed abundantly in VB
      but moderated in VM. Triterpenes were also detected and steroids showed to be
      abundant in VM but moderate in VB. On the other hand, antioxidant capacity
      measured by the DPPH assay showed that VM possesses a stronger antioxidant
      activity than VB with IC50 5.50 ug mL-1. Phenol and flavonoid assays carried out
      by Folin-Ciocalteu and colorimetric test also revealed that methanol extracts of
      both species contain high concentrations of these metabolites. A relationship
      between the antioxidant activity, total phenol and flavonoids content of the
      extracts analyzed was demonstrated in this investigation since those samples with
      higher phenolic concentrations showed likewise higher antioxidant activity.

PMID- 29465908
TI  - Does Plan B work? Home range estimations from stored on board and transmitted
      data sets produced by GPS-telemetry in the Colombian Amazon.
AB  - Telemetry based on Global Positioning Systems (GPS) makes possible to gather
      large quantities of information in a very fine scale and work with species that
      were impossible to study in the past. When working with GPS telemetry, the option
      of storing data on board could be more desirable than the sole satellite
      transmitted data, due to the increase in the amount of locations available for
      analysis. Nonetheless, the uncertainty in the retrieving of the collar unit makes
      satellite-transmitted technologies something to take into account. Therefore,
      differences between store-on-board (SoB) and satellite-transmitted (IT) data sets
      need to be considered. Differences between SoB and IT data collected from two
      lowland tapirs (Tapirus terrestris), were explored by means of the calculation of
      home range areas by three different methods: the Minimum Convex Polygon (MCP),
      the Fixed Kernel Density Estimator (KDE) and the Brownian Bridges (BB). Results
      showed that SoB and IT data sets for the same individual were similar, with fix
      ranging from 63 % to 85 % respectively, and 16 m to 17 m horizontal errors.
      Depending on the total number of locations available for each individual, the
      home ranges estimated showed differences between 2.7 % and 79.3 %, for the 50 %
      probability contour and between 9.9 % and 61.8 % for the 95 % probability
      contour. These differences imply variations in the spatial coincidence of the
      estimated home ranges. We concluded that the use of IT data is not a good option
      for the estimation of home range areas if the collar settings have not been
      designed specifically for this use. Nonetheless, geographical representations of
      the IT based estimators could be of great help to identify areas of use, besides
      its assistance to locate the collar for its retrieval at the end of the field
      season and as a proximate backup when collars disappear.

PMID- 29465909
TI  - [The jaguar Panthera onca (Carnivora: Felidae) in "El Cielo" Biosphere Reserve,
      Tamaulipas, Mexico].
AB  - Information on the ecology of jaguars (Panthera onca) in "El Cielo" Biosphere
      Reserve in Tamaulipas, Mexico is scant and limited to anecdotic records in a
      handful of publications. The objectives of our study were to: a) determine
      population density and structure of jaguars, b) compare their activity patterns
      with that of pumas (Puma concolor), c) ascertain potential prey relative
      abundance, and d) evaluate local resident's perception on loss of domestic
      animals due to jaguar predation. Between April 2013 and April 2014 we conducted
      camera trapping in Gomez Farias Township with a total sampling effort of 8 580
      camera trap days. Besides, we completed 136 semi-structured interviews among
      local residents of Gomez Farias and Llera Townships to gather information on
      domestic animal losses attributed to jaguars and other carnivores. We identified
      eight different jaguar individuals during a complete year of camera-trapping,
      composed of four adult females, one juvenile female, two adult males and one
      juvenile male. We estimated a jaguar density of 5.9 +/- 1.3 jaguars/100 km2.
      Activity patterns for jaguars and pumas were similar as both were nocturnal and
      crepuscular in nature. The most abundant potential prey species for jaguars in
      the study site were Crax rubra, Cuniculus paca, Mazama temama, Odocoileus
      virginianus and Didelphis virginiana; while the rarest were Mephitis macroura and
      Procyon lotor. Interview results suggested that chickens, dogs, and house cats
      were the most consumed domestic animals from all reported losses by local
      residents (n= 107). This study represents the first attempt to describe jaguar
      ecology in "El Cielo" Biosphere Reserve; however, there is a need of additional
      monitoring efforts to determine the current status of jaguars in a larger area in
      order to establish conservation strategies. Finally, this jaguar population may
      have an important role in maintaining the species in the Sierra Madre Oriental
      biological corridor connecting populations in Nuevo Leon and San Luis states in
      Northeastern Mexico.

PMID- 29465910
TI  - [Diversity and biogeographic affinities of sharks, rays and chimaeras
      (Chondrichthyes: Elasmobranchii, Holocephali) of Mexico].
AB  - The diversity of chondrychthyans in Mexico is described. The fauna is composed by
      214 species (111 sharks, 95 rays and 8 chimaeras) and represents 17.3 % of the
      total number of species recorded worldwide. The families with the highest
      diversity comprise: Rajidae (14.5 %), Carcharhinidae (12.1 %), Pentanchidae,
      Triakidae, and Urotrygonidae (5.1 %). In terms of geographical distribution, the
      diversity on the Mexican Pacific slope reaches up to 56.1 % of those species
      inhabiting Mexican marine and brackish waters (120 species, 62 genera, 37
      families and 14 orders); the diversity in the Atlantic slope resulted similar to
      that on the Mexican Pacific with 55.1 % of the species (118 species, 59 genera,
      35 families and 13 orders). The biogeographical affinities of the Mexican
      chondrychthyan fauna are complex with 19.7 % of the species being circumglobal,
      9.9 % transatlantic, 1.9 % transpacific, and 9.4 % endemic to the exclusive
      economic zone. Additionally, 36.6 % of the species recorded so far are endemic to
      the Eastern Pacific coast where the species are similar to those found in the
      Cortez biogeographic province (27.7 %), followed by the Californian (20.7 %),
      Panamanian (19.3 %), Galapagos (5.6 %) and Peruvian-Chilean (8.9 %). Likewise,
      33.3 % are endemic of the Atlantic coast, where species are similar to those
      found in the Caribbean province (31.9 %), followed by the Carolinean (24.4 %) and
      the Brazilian (6.6 %).

PMID- 29465911
TI  - [Updating the larval habitats of Aedes aegypti (Diptera: Culicidae) in Camaguey,
      Cuba].
AB  - Several illnesses of vectorial origin have a great medical and veterinary
      relevance, due to the adaptations developed by the species involved in their
      transmission. To support preventive programs with updated ecological information
      of Ae. aegypti populations, an entomological survey was carried out in three
      Health Areas of Camaguey, Cuba, during low and high rain seasons of 2013. For
      this, we assessed the type and number of positive containers, quantified larvae
      and pupae in positive containers, according to the container location in or
      outside the house. Both the container representativeness percentage and the pupal
      index by specific containers were calculated (PIsC). The total of houses as well
      as the positive habitual-use and non-disposable containers were compared among
      weather seasons, using the non parametric Chi2 test. The existent relationship
      between the total of positive houses and the habitual-use and non-disposable
      container was explored through the test of proportions hypothesis, with a level
      of significance of P <= 0.05. Ae. aegypti colonized 73 different types of
      containers, being habitual-use and non-disposable a 23.2 %. This number included
      76 % of the positive containers. The greatest larvae collections were obtained in
      exterior water tanks and barrels, with important pupal production (PIsC = 3.04
      and 1.75, respectively), and as well as significant differences towards the rainy
      season respect to positive houses (PUIA: Chi2 = 32.89; P = 0.00; PUE: Chi2 =
      127.44; P = 0.00 and PUJAM: Chi2 = 127.44; P = 0.00), and the habitual-use and
      non-disposable container (PUIA: Chi2 = 30.37; P = 0.00; PUE: Chi2 = 37.26; P =
      0.00 and PUJAM: Chi2 = 81.82; P = 0.00). These data reinforce the priority given
      to the control and surveillance actions conducted by the community in their
      respective houses.

PMID- 29465912
TI  - [Population size and behavior pattern of Grus canadensis nesiotes (Aves: Gruidae)
      in two localities of Cuba].
AB  - The availability of information on species abundance in the Neotropic is
      insufficient, and this prevents the execution of precise analysis and the
      definition of adequate conservation strategies for endemic and threatened
      species. This study aimed to analyze the population size of the endemic and
      threatened subspecies Grus canadensis nesiotes. For this, a simultaneous census
      was undertaken in 24 count stations in Isla de la Juventud (IJ) and 32 stations
      in Ciego de Avila (CA), Cuba, during two consecutive days between 2008 and 2010.
      Abundance and behavior pattern (instantaneous method) were analyzed by habitat
      type, to help understand how cranes modify their behavioral pattern when the
      natural habitat is changed. Flocks in IJ had three individuals, and between 1.9
      +/- 1.5 and 2.8 +/- 1.5 in CA. Population size in IJ was 164 individuals, and in
      CA of 137, 141 and 168 individuals for the 2008-2010 period, respectively. The
      counting efficacy was high (IJ: 91 %; CA: 81-87 %) and the numerical concordance
      was intermediate (IJ: 45.4 %; CA: 72 %). When comparing the habitat type, the
      abundance was higher in natural savannahs (83), followed by coastal flats (59),
      pines (23) and cattle pastures (7) in IJ; while in CA, marsh grasslands hosted
      the greatest abundance for the three years period (130; 120; 112), followed by
      grassland with palms (2; 17; 51) and cattle pastures (5; 4; 5). The cranes were
      fed more in cattle pastures and were more alert in natural savannas and marsh
      grasslands. The frequency of feeding and alert behaviors was different from the
      natural savannah/coastal flats and natural savannah/cattle pastures combinations
      in IJ. For CA, differences were found between marsh grasslands and marsh
      grasslands with palms. The population size increased by management strategies
      adopted in CA; nevertheless, might be affected by habitat loss associated with
      invasive alien plants in IJ. We propose the maintenance of prescribed fire in
      marsh grasslands under protection regime, as a strategy for long-term management
      to contribute with population growth.

PMID- 29465913
TI  - Molecular diagnosis and intraspecific genetic variability of root pathogens of
      arid legumes in Western Rajasthan, India.
AB  - The productivity of arid legumes, such as Clusterbean (Cyamopsis tetragonoloba),
      Cowpea (Vigna unguiculata), Moth bean (Vigna aconitifolia) and Horse gram
      (Macrotyloma uniflorum), may remain stagnant over decades because of their high
      susceptibility to root diseases. Besides, there is a limitation on the
      information about molecular diagnosis and intraspecific genetic variability of
      root pathogens in arid legumes. To contribute in this field, we assessed a total
      of 52 isolates from 88 root samples that were found infected with fungal
      pathogens in Jodhpur, Jaipur and Bikaner Districts of Rajasthan. Diseased roots
      samples were analyzed following standard microbiological methods for fungus
      extraction and purification, and for genetic studies. Irrespective of the
      geographical location from where the diseased samples were collected, all
      pathogen isolates were clustered in RAPD dendrograms as per their respective
      genera. Phylogram, based on multiple sequence alignment, revealed that different
      genera (i.e. Fusarium, Neocosmospora and Syncephalastrum), separated from each
      other, and species within the same genera, clustered together with their
      reference sequences with apreciable bootstrap values. Out of 20 representative
      isolates representing each cluster and all outgroups sequenced, eight were
      molecularly identified as Neocosmospora vasinfecta, five as Fusarium solani, two
      as Neocosmospora striata, two as Fusarium acutatum, one as Syncephalastrum
      monosporum, one as Fusarium oxysporum and one as Fusarium species. The root
      pathogens of the arid legumes were found neither restricted to a geographical
      location nor were host specific in nature. Fusarium solani wilt in cowpea and
      seedling rot in moth bean, F. oxysporum wilt in moth bean, F. acutatum damping
      off in cowpea and Clusterbean, Fusarium sp. seedling rot in Clusterbean,
      Neocosmospora striata root rot in cowpea and wilt in Clusterbean and
      Syncephalastrum monosporum root rot in Clusterbean were molecularly identified as
      new fungal records as pathogens causing root diseases in arid legumes.

PMID- 29465914
TI  - Profile of plasmatic progesterone on pregnancy, and the postpartum estrus of
      Dasyprocta prymnolopha (Rodentia: Dasyproctidae).
AB  - The agouti (Dasyprocta sp.) is a hystricomorph rodent found in some regions of
      the Americas. It is an important cynegetic species, which indicates that the
      overhunting is a threat to their conservation. Very little is known about this
      wildlife in relation to what already has been studied in domestic animals. Thus,
      the knowledge on reproduction of wildlife becomes necessary and essential for the
      management and conservation of these natural resources. Specifically, studies
      regarding hormonal monitoring are important as a basic tool for research in
      modern reproductive biotechnology, and currently, there is no information on the
      progesterone changes during pregnancy of Dasyprocta sp., compared to other
      hystricomorphs. The aim of this study was to describe the profile of plasmatic
      progesterone during pregnancy, and report the restart of ovarian cycle in agouti
      after parturition. For this purpose, 18 black-rumped agoutis (Dasyprocta
      prymnolopha) born in captivity were used, and one or more consecutive pregnancies
      were observed. Copulation was confirmed by the presence of spermatozoa observed
      in the colpocytological examination. Blood samples were collected two times per
      week, and concentrations of progesterone, assessed in ten agoutis, were
      determined by radioimmunoassay. The onset of ovarian activity in six females was
      observed daily by colpocytological examination, starting on the seventh day
      postpartum. The gestational period observed in this study was 104.04 days (SD =
      1.31) (101-106 days) (Number of cases, N = 26), and the interval between births
      was 126.03 days (SD = 18.40) (109-184 days). The plasmatic profile of
      progesterone during pregnancy showed a progressive increase from the 1st to the
      5th week. The higher progesterone levels over this period (6.88 ng / mL, SD =
      3.01) were detected in the 5th week. This value was similar (One-Way ANOVA, p >
      0.05) to that observed in the 4th and 6th weeks, but was statistically different
      (One-Way ANOVA, p < 0.05) when compared to the other weeks. After the 6th week
      there was a progressive decrease in plasmatic progesterone levels. The animals
      showed a postpartum estrus of 12.04 days (SD= 4.29) (7-24 days) (N= 23). It was
      observed that 80.95 % (N= 19) of copulations during this period were fertile.
      This work contributed to understanding the dynamic changes in the progesterone
      levels during the pregnancy in agouti. Nevertheless, more studies are needed for
      a better appreciation of other endocrine and biological changes, in the mother
      and feto-placental unit of the agouti.

PMID- 29465916
TI  - Palestine: the assault on health and other war crimes.

PMID- 29465915
TI  - Seasonal behavior of Thalassia testudinum (Hydrocharitaceae) metabolites.
AB  - The marine angiosperm Thalassia testudinum, commonly known as turtle grass, is a
      dominant seagrass that grows in the Caribbean Sea shelf associated to Syringodium
      filiforme. The hydroalcoholic extract of T. testudinum is rich in polyphenols;
      the most abundant metabolite in this extract is thalassiolin B, a glycosilated
      flavonoid with skin damage repairing properties, and antioxidant capacity among
      others. The present study aimed at generating information about the seasonal
      behavior of secondary metabolites, as well as to study the antioxidant capacity
      of the T. testudinum leaves extract, collected monthly during 2012 from the
      Northeast coastline of Havana, Cuba. For this study, spectrophotometric methods
      were used to determine the concentrations of polyphenols, flavonoids,
      anthocyanins, soluble carbohydrates and proteins, chlorophylls a and b, and
      antioxidant activity of the extracts. In general, results demonstrated seasonal
      variations of the analyzed parameters. Extracts prepared from the vegetal
      material collected in October and November showed the highest values of
      polyphenols (58.81 +/- 1.53 and 52.39 +/- 0.63 mg/g bs, respectivally) and
      flavonoids (44.12 +/- 1.30 and 51.30 +/- 0.67 mg/gdw, respectively). On the
      contrary, the lowest values of polyphenols were found in extracts of leaves
      collected in July and August (15.51 +/- 0.84 and 13.86 +/- 0.48
      mg/g,respectively). In accordance with these results, the lower value of
      Inhibitory Concentration (IC50) was obtained to get a 50 % of maximal effect on
      free radical scavenging activity with the extracts prepared from leaves collected
      in October and November, and less significant IC50 was obtained from the extract
      prepared from leaves collected in August (5.63 mg/mL). A negative correlation (r=
      -0.694) was observed in this study between the content of polyphenols and the
      IC50 necessary to get the half of its antioxidant maximal effect. The high
      correspondence between the maximum values of polyphenols, flavonoids,
      carbohydrates and proteins in October and November, revealed a close relationship
      between these metabolites found in the extract of T. testudinum. Our hypothesis
      about the annual variation in the concentration of these metabolites was
      validated; and these results will support the correct harvesting of T. testudinum
      leaves for biotechnology and industrial purposes.

PMID- 29465917
TI  - [Altitudinal distribution, richness and composition of bird assemblages in a
      mountainous region in Southern Nayarit, Mexico].
AB  - Elevation gradient studies have strengthened the evaluation of changes in
      richness and composition of bird assemblages. They also provide information on
      environmental variables that determine bird distribution, and the variables that
      define their population structure. Our aim was to describe their variation
      through an elevational cline in Southern Nayarit, Mexico. To analyze the behavior
      of richness across the gradient, we gathered information through point counts in
      nine elevational intervals (300 m from each other) from sea level to 2 700 m of
      elevation. With a standardized sampling effort, we produced rarefaction curves
      and analyzed changes in species composition by hierarchical classification using
      the TWINSPAN technique. In order to identify variables associated with richness
      changes, we examined the effect of precipitation and habitat structure via
      regression trees. An analysis of nonmetric multidimensional scaling (NMDS) was
      implemented with the purpose to determine if the changes in composition
      correspond to changes in vegetation types. Species richness varied significantly
      across the gradient: high in the lower parts of the gradient, reached its peak in
      the middle, and decreased monotonically with elevation. Species responded to
      changes in the cline and were grouped in three elevational zones. Analyses
      suggest that changes in richness and species composition are influenced by
      vegetation, its structure and precipitation regime, as well as various aspects
      related to habitat features and disturbance. These aspects should be taken into
      account in order to design appropriate strategies for the conservation of the
      birds of Nayarit.

PMID- 29465918
TI  - Large mammal community composition and density under a disturbance gradient in
      Northeast Costa Rica.
AB  - Large mammal communities, integral components of Neotropical ecosystems, are
      increasingly threatened by habitat fragmentation and degradation due to
      anthropogenic pressures and climate change. Lowland Neotropical palm forests
      harbor diverse mammal communities, including threatened and endangered species.
      We monitored three transects in the Barra del Colorado Wildlife Refuge in
      Northeast Costa Rica from February 2014 until April 2015 documenting large
      terrestrial mammal and primate detections. Following established large mammal
      survey methodology, each transect was walked weekly alternating between early
      morning and late afternoon to maximize detection. The three transects represent
      three levels of anthropogenic disturbance with highest disturbance at the Cerro,
      followed by Cano Palma Biological Station (CPBS), and lowest levels in Tortuguero
      National Park (TNP). Overall we found higher diversity and increased presence of
      endangered species in TNP and the lowest diversity and lower presence of those
      species in the Cerro. Overall we detected 25 species; 19 at the Cerro, 22 in TNP
      and 23 at CPBS. TNP had the highest diversity as calculated by Simpson index
      (28.3) followed by CBPS (27.9), and the Cerro had the lowest diversity of mammals
      (2.27). The most influential species driving the differences of communities
      between the three transects included the white-lipped and collared peccaries,
      which were both present in higher densities in transects with lower disturbance
      and higher levels of protection, and domestic dogs which were present in higher
      densities at the Cerro. This study has documented baseline densities of large
      mammal communities in the wildlife refuge which can be used as preliminary data
      for future comparisons. As development is continuing in the region, including
      construction of a tourist trail at the Cerro, a continued monitoring is
      recommended to understand the effect of development on mammal communities.

PMID- 29465919
TI  - Seedling growth and survival of five tree species in secondary forests and
      adjacent pastures in the montane rain forests of Southern Costa Rica.
AB  - Successful forest restoration in tropical environments is limited by the paucity
      of studies on the initial establishment and early survival requirements of
      seedlings of most native tropical tree species under disturbed conditions. Here,
      we evaluated the initial growth responses and the regeneration potential of
      seedlings of five tree species native to Costa Rica (Hasseltia floribunda, Inga
      densiflora, Persea americana, Tapirira mexicana and Trichilia pittieri).
      Seedlings were grown in secondary forests and adjacent open pastures under
      contrasting conditions of light availability. We quantified seedling growth,
      survival and herbivory from August 2010 to August 2011 on a monthly basis, and
      measured differences in leaf mass per area (LMA) at the end of the experiment. We
      found significant variation in growth responses between the understory of
      secondary forests and pastures. Growth in height was highest in pastures across
      all species, with I. densiflora, P. americana and T. mexicana showing the most
      striking differences. In contrast, H. floribunda and T. pittieri did not show
      differences in diameter growth between environments. Except for T. mexicana,
      herbivory increased throughout the experiment in all the species. Herbivory
      increased faster in pastures for H. floribunda and T. pittieri and showed higher
      rates in the forest understory for I. densiflora and P. americana. Seedling
      survival showed significant differences for all species across environments.
      Survival of H. floribunda and I. densiflora was higher in secondary forests,
      whereas the other species showed higher survival in pastures. Leaf mass per area
      showed higher values in the pastures across all species, it suggests that
      individuals exposed to high light conditions had great photosynthetic rate and
      great leaf construction capacity. Due to their rapid growth and high survival, I.
      densiflora and T. mexicana showed great potential to restore abandoned pastures
      and secondary forests. Increasing our knowledge on the response of seedlings
      under disturbed conditions in tropical ecosystems is critical for improving the
      restoration of altered environments by matching the ecological amplitude of
      native species with specific environmental conditions.

PMID- 29465920
TI  - Shell shape variation of queen conch Strombus gigas (Mesograstropoda: Strombidae)
      from Southwest Caribbean.
AB  - The endangered species Strombus gigas is a marine gastropod of significant
      economic importance through the Greater Caribbean region. In contrast to
      phenotypic plasticity, the role of genetics on shell variations in S. gigas has
      not been addressed so far, despite its importance in evolution, management and
      conservation of this species. This work used geometric morphometrics to
      investigate the phenotypic variation of 219 shells of S. gigas from eight sites
      of the Colombian Southwest Caribbean. Differences in mean size between sexes and
      among sites were contrasted by analysis of variance. Allometry was tested by
      multivariate regression and the hypothesis of common slope was contrasted by
      covariance multivariate analysis. Differences in the shell shape among sites were
      analyzed by principal component analysis. Sexual size dimorphism was not
      significant, whereas sexual shape dimorphism was significant and variable across
      sites. Differences in the shell shape among sites were concordant with genetic
      differences based on microsatellite data, supporting its genetic background.
      Besides, differences in the shell shape between populations genetically similar
      suggest a role of phenotypic plasticity in the morphometric variation of the
      shell shape. These outcomes evidence the role of genetic background and
      phenotypic plasticity in the shell shape of S. gigas. Thus, geometric
      morphometrics of shell shape may constitute a complementary tool to explore the
      genetic diversity of this species.

PMID- 29465921
TI  - Permanent germinal epithelium and reproductive cycle of Atractosteus tropicus
      (Lepisosteiformes: Lepisosteidae) males, Tabasco, Mexico.
AB  - The tropical gar A. tropicus plays an important ecological role as it regulates
      other fish stocks in different water bodies in Southeastern Mexico. Nevertheless,
      wild populations are declining, and one conservation alternative is the
      aquaculture production and basic knowledge of reproductive biology; for males,
      this requires the study of germ and somatic structures of testes, to characterize
      the reproductive cycle, and to provide basic knowledge for exploitation and
      conservation models and strategies. With this aim, a total of 24 males with an
      average Lp = 47.2 cm were collected from wild populations from the Laguna
      Pomposu, municipality of Jalpa de Mendez (18 degrees 19' - 93 degrees 01'12" W),
      Tabasco, Mexico. Fish were collected with a trawl net and were transported live
      to the Tropical Aquaculture Laboratory, Division Academica de Ciencias Biologicas
      (DACBiol), Universidad Juarez Autonoma de Tabasco (UJAT). Males were slaughtered
      by prolonged immersion in MS222. Testes samples were collected from each specimen
      and were processed using the standard histological procedures, that consisted of
      dehydration in an ascending ethanol series, xylol, embedding in paraffin,
      sectioning at 7 um, and staining with hematoxylin-eosin (HE). The diameter of 20
      seminiferous tubules (Tse), height of germinal epithelium (Egl), gonadosomatic
      index (IGS) and gonad volume (gV) were determined monthly. Based on morphometric
      and morpho-physiological characteristics, the testes consisted of a network of
      anastomosed tubules with non-restricted cystic spermatogenesis, and a permanent
      germinal epithelium. This is the first report of a permanent germinal epithelium
      in A. tropicus. Five reproductive classes were histologically identified: Class I
      Regressed; Class II Early Maturation; Class III Mid Maturation; Class IV Late
      Maturation; Class V Regression. Monthly GSI, gV and Tse values were lower in
      January and February, the testis showed spermatozoa remains and a regenerating
      discontinuous germinal epithelium. In March spermiogenesis increased and
      proliferation of spermatogonia decreased. Male tropical gar followed a seasonal
      reproductive cycle, indicated by the monthly variation of the reproductive
      classes and the reproductive season processes observed, and for which temperature
      and rainfall seem to stimulate reproductive activity and spermiation.

PMID- 29465940
TI  - [Evaluation of PAE and AE for identifying generalized tracks using snakes in
      Hidalgo, Mexico].
AB  - One of the most important concepts in Panbiogeography is the generalized track,
      which represents an ancestral biota fragmented by geological events that can be
      recovered through several methods, including Parsimony analysis of endemicity
      (PAE) and endemicity analysis (EA). PAE has been frequently used to identify
      generalized tracks, while EA is primarily designed to find areas of endemicity,
      but has been recently proposed for identifying generalized tracks as well. In
      this study we evaluated these methods to find generalized tracks using the
      distribution of the 84 snake species of Hidalgo. PAE found one generalized track
      from three individual tracks (Agkistrodon taylori, Crotalus totonacus and
      Pliocercus elapoides), supported by 89 % of Bootstrap, and EA identified two
      generalized tracks, with endemicity index values of 2.71-2.96 and 2.84-3.09,
      respectively. Those areas were transformed to generalized tracks. The first
      generalized track was retrieved from three individual tracks (Micrurus bernadi,
      Rhadinaea marcellae and R. quinquelineata), and the second was recovered from two
      individual tracks (Geophis mutitorques and Thamnophis sumichrasti). These
      generalized tracks can be considered a unique distribution pattern, because they
      resembled each other and agreed in shape. When comparing both methods, we noted
      that both are useful for identifying generalized tracks, and although they can be
      used independently, we suggest their complementary use. Nevertheless, to obtain
      accurate results, it is useful to consider theoretical bases of both methods,
      along with an appropriate choice of the size of the area. Results using small
      grid size in EA are ideal for searching biogeographical patterns within
      geopolitical limits. Furthermore, they can be used for conservation proposals at
      state level where endemic species become irreplaceable, and where losing them
      would imply the extinction of unique lineages.

PMID- 29465941
TI  - [Effects of human disturbance on the population dynamics of Ocypode quadrata
      (Decapoda: Ocypodidae) in beaches of the Mexican Caribbean].
AB  - The ghost crab Ocypode quadrata is a relevant species in the Western Atlantic
      beaches, and has been proposed as an indicator of human impact in these
      ecosystems. Eventhough some studies have covered various aspects of its natural
      history, no evaluations on the effects of human disturbance on its population
      dynamics have been made. This work compared the abundance, growth, and mortality
      of O. quadrata in two disturbed beaches (Aventuras and Majahual) and two
      preserved beaches (Xcacel and Puerto Angel) from the Mexican Caribbean. For this,
      nine samplings were made on each beach (every two to three months) between March
      2013 and November 2014. Crabs were collected manually by three people, during the
      night first hours and for one hour, and a total area of 9 000 m2 per beach. The
      crabs were measured, weighed, and separated into three groups: juvenile, male and
      female; while abundance was estimated by the number of collected crabs, and
      growth parameters were estimated using length frequencies. A total of 1 047 crabs
      were sampled in the four beaches; a higher crab abundance was found in the
      preserved beaches, but significant differences were only found between Puerto
      Angel and Majahual (Tukey, p<0.05). The adult-juvenile ratio was 1:1 in Xcacel
      and Aventuras, while in Majahual, more juveniles than adults were collected; and
      Puerto Angel had more adults than the juveniles. The size structure at Xcacel
      ranged from 4-32 mm, but in the rest of the beaches the minimum size was 5 mm.
      The maximum size at Aventuras, Majahual and Puerto Angel were 27 mm, 25 mm and 30
      mm, respectively. The modal progression analysis of length's pooled data,
      revealed the presence of at least two groups of ages in all beaches. For all
      beaches, individuals smaller than 10 mm length were collected in almost all
      sampling months, indicating a continuous recruitment throughout the year. The
      length-weight relationship of the ghost crab was found isometric in the two
      preserved beaches, and negative allometric at the two impacted beaches. Crabs
      from Puerto Angel showed the highest body condition (Tukey, p<0.05). K-values
      ranged from 0.6-0.97/year and Linfinity from 29.0 mm to 33.6 mm with higher
      values for the two preserved beaches. The highest mortality values were found in
      Xcacel and Aventuras. In the disturbed beaches, the destruction of the dunes, the
      mechanical cleaning and the removal of organic matter, seem to be the main causes
      that lead to a low abundance of crabs, their slower growth and higher
      mortalities. However, in the best preserved beaches, biological interactions
      appear to be the most important aspects in regulating the population dynamics of
      this species. These results supported the information that the ghost crab is a
      good indicator of human disturbance, and its population changes were clearly
      measurable and comparable among protected and impacted beaches; these results are
      also relevant for the management of sandy beaches in the Mexican Caribbean.

PMID- 29465942
TI  - [Reproductive aspects of Pomacea flagellata (Mollusca: Ampullariidae) at Bacalar
      lagoon, Quintana Roo, Mexico].
AB  - The freshwater snail Pomacea flagellata is native from Southeastern Mexico.
      Studies about this species are scarce and none has treated their reproduction.
      This snail has been exploited at Bacalar lagoon for many years, leading to a
      significant decrease in their abundance and currently, a permanent ban was
      proposed by the government. This work aimed to assess the temporal variations of
      mating frequency and the abundance of egg clutches of P. flagellata at Bacalar
      lagoon, as well as their relation with snails density and environmental
      variables. Sampling was done during the three climatic seasons: Rainy (July,
      August and September/2012), North or Cold fronts (December/2012 and January and
      February/2013) and Dry (March, April and May/2013) in 12 sampling stations
      located along the Bacalar lagoon. On each station a transect of 100 m length was
      set parallel to the edge, and the number of fresh egg clutches (pink color) laid
      over vegetation, rocks or manmade structures, were counted. In the water, three
      50 x 2 m transects were set and the number of snails were counted as well as the
      mating frequency. Density of snails varied significantly among seasons,
      decreasing from the rainy to the dry season. There were no significant
      differences of snail abundance among months, nested in climatic seasons (ANOVA,
      p>0.05). During the rainy season the mating frequency was significantly higher
      than in the Norths, meanwhile in the dry season no mating were registered
      (Kruskal-Wallis, p?0.05). Eggs clutches appeared from July to March. Density of
      egg clutches presented no differences between the Rainy and the North seasons
      (2.72 and 2.93 clutches/m, respectively), nonetheless during the dry season
      abundance of egg masses was significantly lower (0.1 clutches/m) (H, p?0.05).
      Mating frequency was related with snail abundance (rs= 0.26; p<0.05) and water
      temperature (rs= 0.34; p<0.05) and the abundance of egg masses is related with
      snail abundance (rs= 0.46; p<0.05). In general, we observed that reproductive
      activity of P. flagellata at Bacalar lagoon is related with the warmer months and
      with higher rainfall. This finding is relevant to support the management of this
      resource in the region, so that to implement any management arrangement they must
      be aware that a temporal ban is necessary during the reproductive season at
      least.

PMID- 29465943
TI  - Water absorption and method improvement concerning electrical conductivity
      testing Acacia mangium (Fabaceae) seeds.
AB  - Acacia is an important forest species of rapid growth whose seeds have tegument
      dormancy. In this work it was intended to characterize water absorption pattern
      after seed dormancy break, and to determine the amount of water, container size
      and the need of breaking the tegument dormancy, as to perform electrical
      conductivity test in small and large seeds of Acacia mangium (Fabaceae). The
      seeds were collected from 10, 8 and 6 years old trees established in poor
      yielding-capacity soils on savannah areas of Roraima, Brazil; seeds were
      classified in six lots concerning to seed size and tree age. Germination tests
      (50 seeds and four replications per lot) were carried out on germitest(r) paper
      maintained on gerbox at 25  degrees C. Imbibition was verified by seed weighing
      at different times (0, 2, 5, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96 and 120
      hours). The electrical conductivity test consisted of three experiments,
      distinguished by the amount of water used and by the container size in which
      seeds were immersed. Seeds of A. mangium coming from 10 years old trees presented
      increased germination percent and germination speed than seeds of six-year old
      trees. Small seeds presented increased in electrical conductivity and water
      absorption until 120 hours when compared to large seeds. The immersion of seeds
      of A. mangium in 40 mL of distilled water into 180 mL plastic containers, after
      dormancy break, it is indicated for the determination of electrical conductivity
      test. The ratio of electrolytes by seed mass, after 24 hours of immersion in
      water, turns electrical conductivity test more accurate concerning A. mangium
      seeds.

PMID- 29465944
TI  - Using indigenous knowledge to link hyper-temporal land cover mapping with land
      use in the Venezuelan Amazon: "The Forest Pulse".
AB  - Remote sensing and traditional ecological knowledge (TEK) can be combined to
      advance conservation of remote tropical regions, e.g. Amazonia, where intensive
      in situ surveys are often not possible. Integrating TEK into monitoring and
      management of these areas allows for community participation, as well as for
      offering novel insights into sustainable resource use. In this study, we
      developed a 250 m resolution land-cover map of the Western Guyana Shield
      (Venezuela) based on remote sensing, and used TEK to validate its relevance for
      indigenous livelihoods and land uses. We first employed a hyper-temporal remotely
      sensed vegetation index to derive a land classification system. During a 1 300
      km, eight day fluvial expedition in roadless areas in the Amazonas State
      (Venezuela), we visited six indigenous communities who provided geo-referenced
      data on hunting, fishing and farming activities. We overlaid these TEK data onto
      the land classification map, to link land classes with indigenous use. We
      characterized land classes using patterns of greenness temporal change and topo
      hydrological information, and proposed 12 land-cover types, grouped into five
      main landscapes: 1) water bodies; 2) open lands/forest edges; 3) evergreen
      forests; 4) submontane semideciduous forests, and 5) cloud forests. Each land
      cover class was identified with a pulsating profile describing temporal changes
      in greenness, hence we labelled our map as "The Forest Pulse". These greenness
      profiles showed a slightly increasing trend, for the period 2000 to 2009, in the
      land classes representing grassland and scrubland, and a slightly decreasing
      trend in the classes representing forests. This finding is consistent with a gain
      in carbon in grassland as a consequence of climate warming, and also with some
      loss of vegetation in the forests. Thus, our classification shows potential to
      assess future effects of climate change on landscape. Several classes were
      significantly connected with agriculture, fishing, overall hunting, and more
      specifically the hunting of primates, Mazama americana, Dasyprocta fuliginosa,
      and Tayassu pecari. Our results showed that TEK-based approaches can serve as a
      basis for validating the livelihood relevance of landscapes in high-value
      conservation areas, which can form the basis for furthering the management of
      natural resources in these regions.

PMID- 29465945
TI  - [Edge effect on lichen's distribution and chlorophyll content, in fragments of
      Polylepis quadrijuga (Rosaceae) in Paramo de la Rusia (Boyaca-Colombia)].
AB  - The ecosystems fragmentation is one of the anthropic phenomena with highest
      impact at global level and the edge effect causes that only the fragments
      interior conserve their original biotic and abiotic characteristics. Lichens are
      organisms especially susceptible to environmental variability, what could be
      useful for bio-indication of edge effect. In this work, we evaluated the edge
      effect in two fragments of Polylepis quadrijuga in the Paramo de la Rusia (Boyaca
      Colombia) to determine if there is an edge effect on distribution of lichens
      associated to P. quadrijuga and their chlorophyll content. We used three
      transects of 70 m across the matrix-edge-interior gradient in each fragment. We
      chose nine phorophytes per transect to measure the environmental variables:
      photosynthetically active radiation, relative humidity and air temperature, and
      the biological variables: richness and cover per species. Besides, we employed
      the species that were present in all the three zones of the gradient to quantify
      the content of chlorophylls a and b, and determine if there are changes in the
      ratio of chlorophylls a/b that could suggest physiological plasticity as a
      response to the edge effect. Our results showed that fragment 2 had a higher edge
      exposition because of its high relation perimeter/area, allowing to an
      environmental homogenization and lose of biodiversity in relation with fragment
      1. Overall, we found 55 differentially distributed species in relation with the
      fragments and the matrix-edge-interior gradient. The interior of fragment 1 was
      the most conserved zone, harboring a composition different in more than 40 % to
      the composition of any other zone. We classified the lichens according with their
      habits: gelatinous, fruticose, crusty or foliose, but we did not find any
      relationship between the habit distribution and the edge effect. Six species of
      wide distribution showed changes in the chlorophyll content along the matrix-edge
      interior gradient, what is an evidence of physiological plasticity to edge
      effect. It was also possible to distinguish between species with preference to
      warmer environment and species with preference to more humid and sufficiently
      irradiated places. We concluded that some species of lichens could have an
      important potential as bio-indicators of fragmentation in the paramo.

PMID- 29465946
TI  - [Light environment in the understory of an Andean cloud forest: canopy structure
      and climatic seasonality].
AB  - The light environment in the understory of cloud forests is highly heterogeneous
      and determined by species composition, canopy structure, site conditions, and
      seasonality. This study was carried out at San Eusebio cloud forest, Venezuela (2
      300 - 2 500 masl). The impact of canopy structure variations on understory light
      availability was estimated in the dry (December-February) and rainy (March
      November) seasons, in sites under continuous canopy cover and gaps of various
      sizes. Hemispherical photographs were taken to estimate the percentage of canopy
      openness, leaf area index, percentages of transmitted direct and diffuse light,
      and duration and frequency of sunflecks. A light index was calculated from the
      relative proportions of direct and diffuse light transmitted to the understory.
      For most variables, there were significant differences between seasons, as well
      as among different gap sizes and under closed canopy. The light index was low
      (0.25 to 26 of a maximum = 100), even for the largest gaps, indicating a highly
      shaded light environment, especially beneath closed canopy in the rainy season.
      Patterns and interactions among factors were analyzed (gaps vs. continuous
      canopy, gap sizes, location within the gaps, and seasonality) with a mixed
      effects repeated measures Anova design. Results showed that the amount of light
      reaching the understory is low in both gaps and closed canopy. However, small but
      significant differences in light availability existed for both seasonality and
      magnitude of the perturbations. These differences could contribute to explain the
      dynamics of tree species regeneration in this forest. The knowledge of the
      factors conditioning light availability in the understory where tree regeneration
      begins is crucial in cloud forests because of energetic limitations in this
      ecosystem, and might be essential for future restoration and conservation plans
      concerning the preservation of the diversity and integrity of these forests.

PMID- 29465947
TI  - [Fine root dynamics and its relationship with soil fertility in tropical
      rainforests of Choco].
AB  - The fine roots play an important role in the acquisition of water and minerals
      from the soil, the global carbon balance and mitigation of climate change. The
      dynamics (productivity and turnover) of fine roots is essential for nutrient
      cycling and carbon balance of forest ecosystems. The availability of soil water
      and nutrients has significantly determined the productivity and turnover of fine
      roots. It has been hypothesized that fine roots dynamics increases with the
      availability of soil resources in tropical forest ecosystems. To test this
      hypothesis in tropical rainforests of Choco (ecosystems with the highest rainfall
      in the world), five one-ha permanent plots were established in the localities of
      Opogodo and Pacurita, where the productivity and turnover of fine roots were
      measured at 0-10 cm and 10-20 cm depth. The measurement of the fine root
      production was realized by the Ingrowth core method. The fine root turnover was
      measured like fine roots production divided mean annual biomass. In addition,
      soil fertility parameters (pH, nutrients, and texture) were measured and their
      association with productivity and turnover of fine roots was evaluated. It was
      found that the sites had nutrient-poor soils. The localities also differ in soil;
      Opogodo has sandy soils and flat topography, and Pacurita has clay soils, rich in
      aluminum and mountainous topography. In Opogodo fine root production was 6.50 +/-
      2.62 t/ha.yr (mean +/- SD). In Pacurita, fine root production was 3.61 +/- 0.88
      t/ha.yr. Also in Opogodo, the fine root turnover was higher than in Pacurita
      (1.17 /y and 0.62 /y, respectively). Fine root turnover and production in the
      upper soil layers (10 cm upper soil) was considerably higher. Productivity and
      turnover of fine roots showed positive correlation with pH and contents of
      organic matter, total N, K, Mg, and sand; whereas correlations were negative with
      ECEC and contents of Al, silt, and clay. The percentage of sand was the parameter
      that best explained the variations of fine root production. The fine root
      turnover was negatively explained by soil Al availability. Results suggested the
      increase of fine root dynamics with soil fertility at a local scale, which also
      indicates that under the oligotrophic conditions of soils in tropical
      rainforests, fine roots tend to proliferate rapidly in small patches of soil rich
      in sand and nutrients.

PMID- 29465948
TI  - A living fossil Tetrapus fig wasp (Hymenoptera: Agaoninae) developing in extant
      Neotropical fig species (Moraceae: Ficus, section Pharmacosycea).
AB  - It has been assumed that Tetrapus female wasps (Agaonidae s.s.), the pollinators
      of the figs of the New World, section Pharmacosycea, are mainly characterized by
      the presence of one mandibular appendange only, and that it is the most ancestral
      clade of extant Agaonidae s.s., and the males are tetrapodous. The main objective
      of this work was to study five Tetrapus morphotypes, whose females have two
      mandibular appendages and the males are hexapodous, their fig host association
      and phylogenetic position to the family Agaonidae. The question of which group of
      fig pollinating wasps and associated figs are the sister to the rest of the
      pollinating agaonids, and figs respectively remain open. I report a group of New
      World extant Tetrapus morphotypes (Agaonidae: Agaoninae) provisionally assigned
      to Hexapus subg. nov. in preparation. Currently, Tetrapus appears as the sister
      taxon to all other fig pollinating taxa. Howeveer, morphologically, ecologically,
      geographically and historically Hexapus seems to be the ancestral clade of the
      extant Agaoninae. Hexapus morphotypes develop in fig species of subsection
      Petenenses (section Pharmacosycea). In the known extant Tetrapus, the females
      have one mandibular appendage and the males have reduced one or two short-lobe
      atrophied non-functional midlegs (tetrapodous). Hexapus females have two free
      mandibular appendages, and the males have five segmented functional mid-legs
      (hexapodous). Molecularly Hexapus seems to be the ancestral clade of extant
      Agaoninae; e.g., a Tetrapus sp. of Ficus crassivenosa was placed by other author
      as the ancestral clade of 101 wasp species, representing 19 worldwide Agaoninae
      genera, including four Tetrapus species. In Tetrapus sp. of Ficus crassivenosa,
      the female has two mandibular appendages and the male is hexapodous. The females
      of T. apopnus and T. delclosi, preserved in Early to mid-Miocene amber from the
      Dominican Republic, also have two mandibular appendages and the general
      morphology of extant Hexapus. I suggest that Hexapus stands up as a living fossil
      and the sister clade of Tetrapus s.s. The presence of extant Hexapus; as well as
      extant Tetrapus and their fig host species, especially in South America supports
      a Southern Gondwanaland origin for both of them, but not a trans-Pacific
      migrating connection with tropical America for section Pharmacosycea (the host of
      Tetrapus and Hexapus), a long oceanic dispersal, high levels of stem extinction
      of Tetrapus or Atlantic land connections, as proposed by other authors. However,
      lastly it has been assumed that figs and their pollinators arose simultaneously
      in Eurasia during early Tertiary and spread southwards from it. Most of the
      morphological and molecular studies of the fig biology of Agaoninae and Ficus,
      did not include Hexapus morphotypes and their fig hosts, and assumed that
      Tetrapus is the most ancestral clade of the extant fig pollinating wasps.

PMID- 29465949
TI  - [Acute lethal effect of the commercial formulation of the insecticides
      Imidacloprid, Spinosad y Thiocyclam hidrogenoxalate in Bombus atratus
      (Hymenoptera: Apidae) workers].
AB  - The effect of insecticides on bees has gained great attention, however, there are
      few studies that explore this issue on Neotropical bees. Bombus atratus is a
      neotropical species broadly distributed in Colombia and is considered an
      important pollinator of both Andean ecosystems and agroecosystems. However, as
      for many wild bees species, the effect of insecticides on B. atratus is unknow.
      In this study we determined the acute median lethal dose (LD50) of commercial
      formulations of insecticides Imidacloprid, Spinosad and Thiocyclam hydrogen
      oxalate, widely used in Colombia to control several pests of important crops. The
      LD50 was carried out by oral and contact routes, following and modifying the EPPO
      and OECD guidelines to perform LD50 on A. mellifera. We evaluated five doses for
      each route and insecticide, in a total of 25 medium-size workers for each dose by
      duplicate. Mortality was registered at 24, 48 and 72 hours after the experiment;
      and data were analyzed with the Probit regression model. For Imidacloprid,
      contacts and oral LD50 were 0.048 ug/bee and 0.010 ug/bee, respectively. For
      Thiocyclam hydrogen oxalate, topical and oral LD50 were 0.244 ug/bee and 0.056
      ug/bee, respectively. For Spinosad, the oral LD50 corresponded to 0.28 ug/bee; it
      was not possible to establish the LD50 for the contact route. The Hazard Quotient
      (HQ) and Index of Relative Toxicity indicated that all three active ingredients
      are highly toxic. We discussed the risk of the insecticides use on B. atratus,
      considering their chemical nature.

PMID- 29465950
TI  - Total protein composition of young and adult Biomphalaria alexandrina snails with
      different compatibilities to Schistosoma mansoni infection.
AB  - Schistosomiasis remains a disease of major global public health concern since it
      is a chronic anddebilitating illness. The widely distributed Schistosoma mansoni
      that causes intestinal schistosomiasis representsa great threat. Its world-wide
      distribution is permitted by the broad geographic range of the susceptible
      species ofits intermediate host, Biomphalaria, which serves as an obligatory host
      for the larval stage, at which humans getinfected. The objectives were to
      identify the proteins responsible for the snails' compatibility outcome
      throughdifferentiation between the total proteins among Biomphalaria alexandrina
      snails at different ages. The workwas conducted on snails that differ in age and
      genetic backgrounds. Four subgroups (F1) from the progeny ofself-reproduced
      susceptible and resistant snails (F0) were studied. Infection rates of these
      subgroups (youngsusceptible, adult susceptible, young resistant and adult
      resistant) were 90 %, 75 %, 40 % and 0 %, respectively.Using Sodium Dodecyl
      Sulphate Polyacrylamide Gel electrophoresis (SDS-PAGE), differences in
      proteinexpression were evaluated between adult and young snails of different
      subgroups. Dice similarity coefficient wascalculated to determine the percentage
      of band sharing among the experimental subgroups. The results showedthat the
      combination of similarities between age and compatibility status of the snails,
      lead to the highest similaritycoefficient, followed by the combination of
      similarities of both genetic origin and age, even though theydiffer in the
      compatibility status. On the other hand, the differences in the genetic
      background, age and compatibilitystatus, lead to the least similarity index. It
      was also found that the genetic background in young snailsplays a major role in
      the determination of their compatibility, while the internal defense system has
      the upperhand in determining the level of adult compatibility. In conclusion, the
      findings of the present work highlightthe great impact of the snail age in
      concomitance with the genetics and the internal defense in the determinationof B.
      alexandrina/S.mansoni compatibility. Future works are recommended, as further
      characterization of theshared protein bands among the studied subgroups is needed
      to clarify their role in host-parasite relationship.

PMID- 29465951
TI  - Anaerobic microbiota: spatial-temporal changes in the sediment of a tropical
      coastal lagoon with ephemeral inlet in the Gulf of Mexico.
AB  - Sulfate-reducing bacteria (SRB) and methanogenic archaea (MA) share common niches
      in coastal sediments during the terminal phases of the anaerobic mineralization
      of organic matter. The purpose of this study was to analyze the spatial -
      temporal variation of SRB and MA in the sediments of a tropical coastal lagoon
      with ephemeral inlet (La Mancha, Veracruz, Gulf of Mexico) and its relationship
      with environmental changes. A total of 24 sediment samples were collected during
      the dry (April, May), rainy (July, September) and Northern (November, February)
      seasons in the period 2013-2014. Microbiological analyses included the
      quantification of the viable SRB and MA with different substrates, as well as
      mineralization experiments to determine the effect of sulfate on acetate
      oxidation. The analyzed environmental variables in the sediments included:
      temperature, pH, Eh, salinity, sulfates, H2S, volatile solids, carbohydrates, and
      granulometric characteristics. Major changes occurred between the dry and rainy
      seasons. During the dry season, sulfate-reducing abundance was significantly
      greater with lactate (8.3x105 - 1.2x107 cells / g) and propionate (1.8x105 -
      6.6x106 cells / g) as substrates, while the MA that use methanol were dominant
      (4.2x105 - 9.1x106 cells / g). In contrast, during the rainy season,
      hydrogenophylic (2.6x105 - 8.3x106 cells/g) and acetoclastic (5.4x105-6.4x106
      cells / g) MA increased significantly and SRB decreased in the analyzed
      substrates. An apparent competition for acetate was observed, with a greater
      oxidation in the media with sulfates in the dry season (0.06 mM acetate / g
      sediment / day), and a greater oxidation in the media without sulfates in the
      rainy season (0.02 mM acetate / g sediment / day). SRB and MA were present
      throughout the sediment column, however SRB dominated in the first centimeters of
      the sediment while MA were abundant in deeper layers. In conclusion, SRB and MA
      together played a role in the mineralization of organic matter in the sediments
      of La Mancha lagoon, with sulfate-reduction dominating in the dry season (closed
      inlet) and methanogenesis during the rainy season (open inlet). Changes in
      rainfall and river input in this lagoon significantly affect salinity and sulfate
      content, the main factors that regulate the dynamics of SRB and MA in the
      sediments.

PMID- 29465952
TI  - One year weekly dynamics of limnological conditions and phytoplankton in Lake
      Bonilla, Costa Rica.
AB  - The detailed response of tropical lake phytoplankton to weather variations has
      been little studied, but it seems that composition varies in response to rain and
      wind variability over the course of the year. In order to gather more evidence on
      this variation, the weekly variability of phytoplankton composition was studied
      in Lake Bonilla, a low land (380 masl) 30 m deep tropical lake, from April 2010
      to May 2011. Temperature variation at several depths was recorded automatically,
      and measurements of dissolved oxygen, water transparency, and nutrients were
      performed several times during the study period. The lake showed a warm
      monomictic pattern, with deep mixing occurring during the hemispherical winter,
      especially after a heavy rain period in December 2010. Phytoplankton was
      dominated by a few species: a colonial Cyanobacteria (Aphanocapsa sp., functional
      group F) and two colonial Chlorococcaceae (Botryococcus braunii and Eutetramorus
      tetrasporus, both in the functional group K). Their relative dominance shifted
      throughout the year, following changes in water column conditions in response to
      weather variations. Although changes in main functional groups indicate a shift
      in resource availability rather than energy, it was clear that attention should
      also be given to particular species adaptations beyond those used for
      establishing functional groups.

PMID- 29465953
TI  - Infectivity of Chordodes nobilii larvae (Gordiida: Nematomorpha).
AB  - The gordiids are freshwater representatives of the parasite phylum Nematomorpha
      that function asa link between aquatic and terrestrial ecosystems. In recent
      years, different ecotoxicologic studies have beenmade with the South-American
      gordiid species, Chordodes nobilii, that have demonstrated the capacity of
      thisgroup to act as a bioindicator of contamination. Despite the Gordiida's
      ecologic relevance, further studies arestill needed to elucidate different
      aspects of the biology of the class, and among those, the infective capacity,a
      parameter that can be evaluated by the infection index mean abundance (IIMA). A
      knowledge of the intrinsicvariability in the infective capacity of C. nobilii
      would warrant priority in order to establish, the range ofacceptable responses
      for normal or standard conditions in the laboratory, and, to compare the criteria
      amongdifferent assays. The objective of this study was to establish a baseline
      value for the infective capacity for C.nobilii larvae, under controlled
      laboratory conditions, by employing the IIMA as the evaluation parameter. Tothat
      end, we analyzed the infective capacity of C. nobilii larvae that had hatched
      from different strings of eggslaid in the laboratory by a total of 12 females.
      The C. nobilii adults were collected from streams within theArgentina Sauce
      Grande basin, between 2006 and 2009. Once in the laboratory, after mating, the
      females wereplaced in individual containers for oviposition. The egg strings
      obtained from each female were cut in 3 mmlong segments; and when free larvae
      were observed, the segments (N= 90) were placed together with 30 Aedesaegypti
      larvae for evaluation of the gordiids' infective capacity. After 72 h, the
      mosquito larvae were observedby microscopy in order to quantify the C. nobilii
      larvae in body cavities. The IIMAs were calculated as the totalnumber of C.
      nobilii larvae present divided by total number of A. aegypti larvae examined. For
      analysis of theIIMAs obtained, the data were grouped according to the female who
      made the original ovoposition. Our resultsenabled the corroboration of an ample
      range of responses in the infective capacity of this species, a
      characteristicthat would normally be linked to the progenitors originating the
      hatch. Because this relationship prevents theestablishment of a baseline for
      making comparisons among assays with gordiids, through the IIMA as a
      responseparameter, we recommend expressing the IIMA values in each assay relative
      to their respective controls. Thesefindings also provide evidence for the greater
      success in infections by certain members of the progeny over others.Finally, on
      the basis of the results obtained from this study, we stress the relevance of the
      use of the IIMAas a decisive aspect to be considered in different studies on the
      biology of Gordiida.

PMID- 29465954
TI  - Sexual and vegetative propagation of the medicinal Mexican species Phyllonoma
      laticuspis (Phyllonomaceae).
AB  - Phyllonoma laticuspis leaves are used in Carrizal de Bravo, Guerrero, Mexico, to
      heal skin lesions such as injuries and smallpox sequelae and to treat diabetes
      mellitus type 2, and organic extracts of these leaves have been reported to exert
      antibacterial effects. High demand of P. laticuspis as a medicinal plant has
      decreased its natural populations, and propagation of the species has not yet
      been reported. Therefore, the purpose of this study was to assess the vegetative
      propagation of the species through cutting and air layering, as well as its
      sexual propagation in a preserved population. For this, concentrations of 1 000,
      4 000 and 6 000 ppm of a commercial root enhancer, with indole butyric acid
      (IBA), and a control treatment without IBA, were applied to the cuttings and air
      layers. Germination was evaluated under light and dark conditions using lots of
      freshly collected seeds and lots of seeds that had been stored for three months
      at 4  degrees C or 24 +/- 2  degrees C. All experiments were performed in a
      completely randomized design. The cuttings did not develop roots in any
      concentration, whereas 100 % of the air layers rooted, displaying vigorous roots
      in the presence of 4 000 ppm IBA, after four month of treatment application.
      Regarding germination, more than 60 % of the freshly collected seeds germinated,
      whereas less than 20 % of the seeds stored at 4  degrees C, and close to 50 % of
      the seeds stored at 24 +/- 2  degrees C germinated under light and dark
      conditions. No significant differences were observed between light and dark
      conditions, so they were categorized as indifferent photoblastic seeds. The
      observed moisture content of 13.5 % and germination behaviour as the response to
      cold storage, suggest that the resultant seed quality was intermediate. P.
      laticuspis propagation for short-term foliage production can be carried out in
      air layers, in populations with a high density of adult plants as a source of
      plant material and for the restoration of disturbed areas, in the same locality.
      On the other hand, large-scale seedling production, medium-term foliage
      production and preservation of species variability can be achieved using seeds.

PMID- 29465955
TI  - [Use of Leersia hexandra (Poaceae) for soil phytoremediation in soils
      contaminated with fresh and weathered oil].
AB  - The oil industry has generated chronic oil spills and their accumulation in
      wetlands of the state of Tabasco, in Southeastern Mexico. Waterlogging is a
      factor that limits the use of remediation technologies because of its high cost
      and low levels of oil degradation. However, Leersia hexandra is a grass that
      grows in these contaminated areas with weathered oil. The aim of the study was to
      evaluate the bacteria density, plant biomass production and phytoremediation of
      L. hexandra in contaminated soil. For this, two experiments in plastic tunnel
      were performed with fresh (E1) and weathered petroleum (E2) under waterlogging
      experimental conditions. The E1 was based on eight doses: 6 000, 10 000, 30 000,
      60 000, 90 000, 120 000, 150 000 and 180 000 mg.kg-1 dry basis (d. b.) of total
      petroleum hydrocarbons fresh (TPH-F), and the E2, that evaluated five doses: 14
      173, 28 400, 50 598, 75 492 and 112 142 mg. kg-1 d. b. of total petroleum
      hydrocarbons weathered (TPH-W); a control treatment with 2 607 mg.kg-1 d. b. was
      used. Each experiment, with eight replicates per treatment, evaluated after three
      and six months: a) microbial density of total free-living nitrogen-fixing
      bacteria (NFB) of Azospirillum (AZP) and Azotobacter group (AZT), for viable
      count in serial plate; b) dry matter production (DMP), quantified gravimetrically
      as dry weight of L. hexandra; and c) the decontamination percentage of
      hydrocarbons (PDH) by Soxhlet extraction. In soil with TPH-F, the NFB, AZP y AZT
      populations were stimulated five times more than the control both at the three
      and six months; however, concentrations of 150 000 and 180 000 mg.kg-1 d. b.
      inhibited the bacterial density between 70 and 89 %. Likewise, in soil with TPH
      W, the FNB, AZP and AZT inhibitions were 90 %, with the exception of the 14 173
      mg.kg-1 d. b. treatment, which stimulated the NFB and AZT in 2 and 0.10 times
      more than the control, respectively. The DMP was continued at the six months in
      the experiments, with values of 63 and 89 g in fresh and weathered petroleum,
      respectively; had no significant differences with the control (p<=0.05). The PDH
      reached values of 66 to 87 % both TPH-F and TPH-W at six months, respectively.
      These results demonstrated the ability the L. hexandra rhizosphere to stimulate
      the high NFB density, vegetal biomass production and phytoremediation of
      contaminated soils (with fresh and weathered petroleum), in a tropical
      waterlogging environment.

PMID- 29465956
TI  - [Immature stages of Amnestus rugosus (Hemiptera: Cydnidae)].
AB  - In Mexico there are 29 species of Amnestus, of which six species are from
      Veracruz. The morphological features and illustrations of immature stages of A.
      rugosus are presented. Notes about the biology and behavior were included. The
      nymphal and adult stages of A. rugosus were found in remnants of riparian
      vegetation of the mesophilous forest in La Antigua river basin, Veracruz, Mexico.
      Twelve sites in five localities were selected and the specimens were sampled in
      rainy (July) and dry (April) seasons of 2012. The samples were processed in
      Berlese-Tullgren funnel and Winkler. A total of 419 individuals, 320 adults and
      99 nymphs of A. rugosus were revised. The size and coloration of the body and
      punctuation patterns the immature stages of A. rugosus, A. ficus, and A.
      morelensis are the main differences among these species. A. rugosus is a first
      record from Veracruz.

PMID- 29465957
TI  - [Effect of management on tree diversity in secondary vegetation in the Biosphere
      Reserve of Calakmul, Campeche, Mexico].
AB  - The tropical dry forest (BTS) of Yucatan Peninsula has been managed forcenturies,
      but the relationship between these management efforts and their effects on trees
      diversity has not beenfully understood. The aim of this study was to evaluate the
      effect of forest management (thinning, harvestingand enrichment of species), in
      the structure of secondary vegetation derived from dry tropical forests, in
      twocommunities in Calakmul, Campeche, Southeast Mexico. We analyzed changes in
      the composition, speciesrichness, species diversity, and structure in secondary
      vegetation subject to following types of management: (1)secondary vegetation with
      beekeeping management (MA), secondary vegetation with forest management
      (MF),natural secondary vegetation (SM) and tropical dry forest (BTS). The species
      composition was similar betweensecondary vegetation managed and unmanaged. On the
      other hand, between managed secondary vegetation andBTS there were differences in
      species composition. Species richness was not different between all conditions.MA
      showed the lowest species diversity and presented higher average density (5 413+/
      770.26 ind.ha-1).MF hadlowest average density (3 289 +/- 1 183.60 ind.ha-1). BTS
      showed the highest average basal area (24.89 +/- 1.56m2.ha-1) regarding the other
      conditions. We concluded that is necessary to keep monitoring the managed areasto
      detect effects of management that may be adverse or favorable to conservation of
      floristic diversity of BTS.

PMID- 29465973
TI  - Impact of daily variable temperatures in life-history traits of tropical anurans.
AB  - Anuran embryos and tadpoles are daily exposed to wide thermal variations in their
      ponds, with maximum temperatures at midday. The aim of this research was to study
      the impact of three daily variable thermal environments (with maximum
      experimental temperatures between 10:00 and 16:00 hours), on the survival,
      developmental time and body size of metamorphs of four tropical anuran species
      from lowland habitats in Colombia. A total of 50 embryos (Gosner stage ten) to
      metamorphosis (Gosner stage 46) of Rhinella humboldti, Hypsiboas crepitans and
      Engystomops pustulosus were exposed to each one of the three daily variable
      temperature treatments: high temperature (mean = 27.5  degrees C; maximum
      temperature = 34 +/- 1  degrees C; range = 23-35  degrees C), medium temperature
      (25.5  degrees C; 29 +/- 1  degrees C; 23-30  degrees C), and low temperature (24
      degrees C; 24 +/- 1  degrees C; 23-25  degrees C). For the other species,
      Espadarana prosoblepon, 40 embryos to metamorphosis were exposed to each one of
      the following thermal treatments: high temperature (mean = 22  degrees C; maximum
      temperature = 25 +/- 1  degrees C; range = 18-26  degrees C), medium temperature
      (20.5  degrees C; 22 +/- 1  degrees C; 18-23  degrees C), and low temperature (19
      degrees C; 19 +/- 1  degrees C; 18-20  degrees C). For all species, the thermal
      variable environment with the highest temperature showed the greatest accumulated
      survival, reduced significantly the developmental time from embryos to
      metamorphs, and the snout-vent-length of metamorphs. Therefore, under field
      conditions where ponds are exposed to thermally variable environments, the
      highest temperatures may promote a decrease in the period of time to
      metamorphosis, and a positive increase for the anuran survival; nevertheless,
      extreme temperatures were also found in the microhabitat of the species studied,
      higher than their upper thermal limits reported, which suggest a vulnerable
      situation for them and other tropical anurans from similar habitats.

PMID- 29465974
TI  - Metal-Organic Framework-Derived Hollow Hierarchical Co3O4 Nanocages with Tunable
      Size and Morphology: Ultrasensitive and Highly Selective Detection of
      Methylbenzenes.
AB  - Nearly monodisperse hollow hierarchical Co3O4 nanocages of four different sizes
      (~0.3, 1.0, 2.0, and 4.0 MUm) consisting of nanosheets were prepared by
      controlled precipitation of zeolitic imidazolate framework-67 (ZIF-67) rhombic
      dodecahedra, followed by solvothermal synthesis of Co3O4 nanocages using ZIF-67
      self-sacrificial templates, and subsequent heat treatment for the development of
      high-performance methylbenzene sensors. The sensor based on hollow hierarchical
      Co3O4 nanocages with the size of ~1.0 MUm exhibited not only ultrahigh responses
      (resistance ratios) to 5 ppm p-xylene (78.6) and toluene (43.8) but also a
      remarkably high selectivity to methylbenzene over the interference of ubiquitous
      ethanol at 225  degrees C. The unprecedented and high response and selectivity to
      methylbenzenes are attributed to the highly gas-accessible hollow hierarchical
      morphology with thin shells, abundant mesopores, and high surface area per unit
      volume as well as the high catalytic activity of Co3O4. Moreover, the size, shell
      thickness, mesopores, and hollow/hierarchical morphology of the nanocages, the
      key parameters determining the gas response and selectivity, could be well
      controlled by tuning the precipitation of ZIF-67 rhombic dodecahedra and
      solvothermal reaction. This method can pave a new pathway for the design of high
      performance methylbenzene sensors for monitoring the quality of indoor air.

PMID- 29465975
TI  - An Integrated Approach Based on a DNA Self-Assembly Technique for
      Characterization of Crosstalk among Combinatorial Histone Modifications.
AB  - Combinatorial histone post-translational modifications (HPTMs) form a complex
      epigenetic code that can be decoded by specific binding proteins, termed as
      readers. Their specific interplays have been thought to determine gene expression
      and downstream biological functions. However, it is still a big challenge to
      analyze such interactions due to various limitations including rather weak,
      transient, and complicated interactions between HPTMs and readers, the high
      dynamic property of HPTMs, and the low abundance of reader proteins. Here we
      sought to take advantage of DNA-templated and photo-cross-linking techniques to
      design a group of combinatorial histone PTM peptide probes for the identification
      of multivalent interactions among histone PTMs and readers. By use of
      trimethylation on histone H3K4 (H3K4me3) and phosphorylation on H3T3, we
      demonstrated that this approach can be successfully utilized for identification
      of the PTM crosstalk on the same histone. By use of H3K4me3 and acetylation on
      H4K16, we showed the potential application of the probe in the multivalent
      interactions among PTMs on different histones. Thus, this new chemical proteomics
      tool combined with mass spectrometry holds a promising potential in profiling of
      the readers of combinatorial HPTMs and characterization of crosstalk among
      multiple PTMs on histones and can be adapted for broad biomedical applications.

PMID- 29465976
TI  - Role of Gastropod Mucus in the Transmission of Angiostrongylus cantonensis, a
      Potentially Serious Neurological Infection.
AB  - Angiostrongylus cantonensis, the rat lungworm, is endemic to Hawaii. A recent
      increase in the number of cases has drawn intense local and national media
      attention. As a result there is an increased fear of acquiring the disease from
      local produce, which has the potential to adversely affect the income of local
      farmers. The most common means of transmission is by the ingestion of an infected
      intermediate host. Other modes of transmission have been suggested including
      infectious larvae being released into the mucus trail of gastropods. This
      literature review indicates that mucus trails from infected gastropods poses a
      minimal risk to humans.

PMID- 29465977
TI  - Potential Utility of Metal-Organic Framework-Based Platform for Sensing
      Pesticides.
AB  - The progress in modern agricultural practices could not have been realized
      without the large-scale contribution of assorted pesticides (e.g.,
      organophosphates and nonorganophosphates). Precise tracking of these chemicals
      has become very important for safeguarding the environment and food resources
      owing to their very high toxicity. Hence, the development of sensitive and
      convenient sensors for the on-site detection of pesticides is imperative to
      overcome practical limitations encountered in conventional methodologies, which
      require skilled manpower at the expense of high cost and low portability. In this
      regard, the role of novel, advanced functional materials such as metal-organic
      frameworks (MOFs) has drawn great interest as an alternative for conventional
      sensory systems because of their numerous advantages over other nanomaterials.
      This review was organized to address the recent advances in applications of MOFs
      for sensing various pesticides because of their tailorable optical and electrical
      characteristics. It also provides in-depth comparison of the performance of MOFs
      with other nanomaterial sensing platforms. Further, we discuss the present
      challenges (e.g., potential bias due to instability under certain conditions,
      variations in the diffusion rate of the pesticide, chemical interferences, and
      the precise measurement of luminesce quenching) in developing robust and
      sensitive sensors by using tailored porosity, functionalities, and better
      framework stability.

PMID- 29465978
TI  - Weaker N-Terminal Interactions for the Protective over the Causative Abeta
      Peptide Dimer Mutants.
AB  - Knowing that abeta amyloid peptide (Abeta42) dimers are the smallest and most
      abundant neurotoxic oligomers for Alzheimer's disease (AD), we used molecular
      simulations with advanced sampling methods (replica-exchange) to characterize and
      compare interactions between the N-termini (residues 1-16) of wild type (WT-WT)
      and five mutant dimers under constrained and unconstrained conditions. The number
      of contacts and distances between the N-termini, and contact maps of their
      conformational landscape illustrate substantial differences for a single residue
      change. The N-terminal contacts are significantly diminished for the dimers
      containing the monomers that protect against (WT-A2T) as compared with those that
      predispose toward (A2V-A2V) AD and for the control WT-WT dimers. The reduced
      number of N-terminal contacts not only occurs at or near the second residue
      mutations but also is distributed through to the 10th residue. These findings
      provide added support to the accumulating evidence for the "N-terminal hypothesis
      of AD" and offer an alternate mechanism for the cause of protection from the A2T
      mutant.

PMID- 29465979
TI  - Nanoscale Studies of Organic Radicals: Surface, Interface, and Spinterface.
AB  - In the last decade technology has brought significant changes to our lives,
      including new habits and a new view on social relationships. These technological
      innovations are based on several factors, one of which is miniaturization. This
      was made possible also due to the discovery and synthesis of new materials with
      characteristics at the nanoscale that are designed for specific purposes. This
      "on purpose" approach, joined to the development of preparation and growth
      methods, has led to use of thin films rather than bulk materials in devices.
      Using thin films makes devices easier to produce, and using films for coating
      protects the devices and gives specific properties to surfaces. For several
      decades thin films, surfaces, and interfaces have been intensively investigated.
      Indeed, device performances rely on the optimized match of thin films of
      different natures, such as organic and inorganic semiconductors and metals for
      contacts. Surprisingly, in comparison, little attention has been devoted to the
      deposition of organic radicals on a substrate. This might be because these
      materials are considered not stable enough for evaporation. In this work, we
      demonstrate that it is possible to evaporate and deposit organic radicals onto
      well-defined surfaces under controlled conditions, without degradation. Using
      soft X-ray spectroscopies, performed also at synchrotrons, we investigate thin
      film processes, surfaces, and interfaces at the nanoscale, when organic radicals
      are deposited on metal and metal oxide surfaces. We suggest how to design organic
      radicals bearing in mind the thermodynamic factors that govern thin film
      stability, with the purpose of obtaining not only a chemically stable radical,
      but also stable thin films. We investigate the thermal and air stability of the
      deposited films, and we explore the influence of the surface/radical chemical
      bond and the role of surface defects on the magnetic moment at the interface. We
      find that organic radicals are physisorbed and keep their magnetic moment on
      inert and passivated surfaces such as Au(111) and Al2O3(1120) single crystals,
      SiO2, and ideal TiO2(110) single crystals, while defective sites such as oxygen
      vacancies or the presence of OH groups lead to chemisorption of the organic
      radicals on the surface with quenching of their magnetic moment. Our work shows
      that the use of X-ray based techniques represents a powerful approach to reveal
      the mechanisms governing complex interfaces, such as radical/metal and
      radical/metal-oxide, where it is important to describe both charge and spin
      behavior (spinterfaces). It also makes it possible to conceive new experiments to
      investigate the magnetic character of the thin films versus their structural
      properties, toward tuning the arrangement of the molecules in films. Controlling
      the molecular arrangement will give the opportunity to tune the mutual position
      and orientation of the molecules, that is, of the single magnetic moments in the
      films, "imprinting" their magnetic properties. A deep understanding of stable
      radical/inorganic spinterfaces may open the way to use radicals in solid state
      devices or as quantum bits with dedicated configurations, as proposed for other
      molecular quantum bits, and in spin-based electronics.

PMID- 29465980
TI  - Reductive Amination Combining Dimethylation for Quantitative Analysis of Early
      Stage Glycated Proteins.
AB  - Due to the critical role glycation plays in many serious pathological conditions,
      such as diabetes, it is of great significance to discover protein glycation at an
      early stage for precaution and prediction of the disease. Here, a method of
      reductive amination combining dimethylation (RAD) was developed for the
      quantification of early-stage glycated proteins. The quantitative analysis was
      first carried out by reducing the samples using NaBH3CN or NaBD3CN, resulting in
      a 1 Da mass shift and the stabilization of early-stage protein glycation. The two
      samples were then digested and isotopically dimethylated to achieve the mass
      shift of 4 m + 3 n ( m represents the number of N-termini and Lys residues, and n
      represents the number of glycated sites) between light- and heavy-labeled
      glycated peptides for quantification. Consequently, the false positive result can
      be removed according to the different mass shifts of glycated peptides and non
      glycated peptides. In quantification of glycated myoglobin, RAD showed good
      linearity ( R2 > 0.99) and reproducibility (CVs <= 1.6%) in 2 orders of magnitude
      (1:10-10:1). RAD was then applied to quantify the endogenous glycated proteins in
      the serum of diabetic patients, revealing significant differences in the
      glycation level between the patients with complicated retinal detachment and
      those without. In conclusion, RAD is an effective method for quantifying
      endogenous glycated proteins.

PMID- 29465981
TI  - Cellulose Abetted Assembly and Temporally Decoupled Loading of Cargo into
      Vesicles Synthesized from Functionally Diverse Lamellar Phase Forming
      Amphiphiles.
AB  - Self-assembled micrometer-scale vesicles composed of lamellar phase forming
      amphiphiles are useful as chemical microreactors, as minimal artificial cells, as
      protocell mimics for studies of the origins of life, and as vehicles for the
      targeted delivery of drugs. Given their varied uses, discovery of a universal
      mechanism that is simple, rapid, and that produces vesicles from a large variety
      of amphiphiles with different chemical and physical properties at high yield is
      extremely desirable. Here we show that cellulose, in the form of cellulose paper,
      facilitates the assembly of membranous vesicles 5-20 MUm in diameter from
      scientifically and technologically important amphiphiles of diverse chemical
      structures and functionality such as fatty acids (fatty acid vesicles),
      amphiphilic diblock copolymers, and amphiphilic triblock copolymers
      (polymersomes). Assembly of vesicles occurred within 90 min of placing the
      amphiphile-coated cellulose paper into aqueous solutions. Varying thermal and
      chemical conditions, however, are required for the high-yield assembly of
      vesicles from the different amphiphiles. The vesicles, when attached to cellulose
      fibers, have membranes that remain unsealed. This topological characteristic of
      the vesicles grown on paper allowed the scalable separation of the process of
      growth from the process of loading cargo (temporally decoupled growth and
      loading). We demonstrate a temporally decoupled process to rapidly produce large
      quantities of protein-loaded polymersomes on the benchtop by using high
      temperatures to accelerate the growth of the polymersomes and subsequently milder
      temperatures during diffusive loading of the protein cargo.

PMID- 29465982
TI  - An Electrokinetic Separation Route to Source Dialysate from Excess Fluid in
      Blood.
AB  - To improve the health of patients with end-stage renal disease, there is a clear
      need for slow, continuous hemodialysis, and the primary barrier to a wearable
      device is the requirement of a large reservoir of dialysate. We describe an
      electrokinetic means of producing dialysate from the excess fluid extant in the
      peripheral blood of patients undergoing therapy. A critical feature of this
      process is the retention of essential components of blood, especially serum
      albumin. In progress toward this goal, we demonstrate the separation of charged
      from neutral species in blood plasma at a branched microchannel junction by ion
      concentration polarization (ICP). Further, we introduce a method that reduces the
      opportunity for damage to proteins and prevents electrode biofouling. The present
      approach results in as high as 99.7% retention of albumin and successful
      separation of neutral metabolites and excess fluid to be utilized as a precursor
      to dialysate.

PMID- 29465984
TI  - Direct Analysis in Real Time Mass Spectrometry for Characterization of Large
      Saccharides.
AB  - Polysaccharide characterization posts the most difficult challenge to available
      analytical technologies compared to other types of biomolecules. Plant
      polysaccharides are reported to have numerous medicinal values, but their effect
      can be different based on the types of plants, and even regions of productions
      and conditions of cultivation. However, the molecular basis of the differences of
      these polysaccharides is largely unknown. In this study, direct analysis in real
      time mass spectrometry (DART-MS) was used to generate polysaccharide
      fingerprints. Large saccharides can break down into characteristic small
      fragments in the DART source via pyrolysis, and the products are then detected by
      high resolution MS. Temperature was shown to be a crucial parameter for the
      decomposition of large polysaccharide. The general behavior of carbohydrates in
      DART-MS was also studied through the investigation of a number of mono- and
      oligosaccharide standards. The chemical formula and putative ionic forms of the
      fragments were proposed based on accurate mass with less than 10 ppm mass errors.
      Multivariate data analysis shows the clear differentiation of different plant
      species. Intensities of marker ions compared among samples also showed obvious
      differences. The combination of DART-MS analysis and mechanochemical extraction
      method used in this work demonstrates a simple, fast, and high throughput
      analytical protocol for the efficient evaluation of molecular features in plant
      polysaccharides.

PMID- 29465986
TI  - Structure-Property Relationships of Amphiphilic Nanoparticles That Penetrate or
      Fuse Lipid Membranes.
AB  - The development of synthetic nanomaterials that could embed within, penetrate, or
      induce fusion between membranes without permanent disruption would have great
      significance for biomedical applications. Here we describe structure-function
      relationships of highly water-soluble gold nanoparticles comprised of an ~1.5-5
      nm diameter metal core coated by an amphiphilic organic ligand shell, which
      exhibit membrane embedding and fusion activity mediated by the surface ligands.
      Using an environment-sensitive dye anchored within the ligand shell as a sensor
      of membrane embedding, we demonstrate that particles with core sizes of ~2-3 nm
      are capable of embedding within and penetrating fluid bilayers. At the nanoscale,
      these particles also promote spontaneous fusion of liposomes or spontaneously
      embed within intact liposomal vesicles. These studies provide nanoparticle design
      and selection principles that could be used in drug delivery applications, as
      membrane stains, or for the creation of novel organic/inorganic nanomaterial self
      assemblies.

PMID- 29465985
TI  - Identification of a Mycothiol-Dependent Nitroreductase from Mycobacterium
      tuberculosis.
AB  - The success of Mycobacterium tuberculosis (Mtb) as a pathogen depends on the
      redundant and complex mechanisms it has evolved for resisting nitrosative and
      oxidative stresses inflicted by host immunity. Improving our understanding of
      these defense pathways can reveal vulnerable points in Mtb pathogenesis. In this
      study, we combined genetic, structural, computational, biochemical, and
      biophysical approaches to identify a novel enzyme class represented by Rv2466c.
      We show that Rv2466c is a mycothiol-dependent nitroreductase of Mtb and can
      reduce the nitro group of a novel mycobactericidal compound using mycothiol as a
      cofactor. In addition to its function as a nitroreductase, Rv2466c confers
      partial protection to menadione stress.

PMID- 29465987
TI  - Bimetallic Ag-Cu Supported on Graphitic Carbon Nitride Nanotubes for Improved
      Visible-Light Photocatalytic Hydrogen Production.
AB  - This work, for the first time, reports visible-light active bare graphitic carbon
      nitride nanotubes (C3N4 NTs) for photocatalytic hydrogen generation, even in the
      absence of any cocatalyst. Upon uniform dispersion of the cocatalysts, Ag-Cu
      nanoparticles, on the well-ordered bare C3N4 NTs, they exhibit twice the H2
      evolution rate of the bare C3N4 NTs. The improved activity is attributed to their
      unique tubular nanostructure, strong metal-support interaction, and efficient
      photoinduced electron-hole separation compared to their bare and monometallic
      counterparts, evidenced by complementary characterization techniques. This work
      reveals that the H2 production rates correlate well with the oxidation potentials
      of the sacrificial reagents used. Triethylamine (TEA) outperforms other
      sacrificial reagents, including triethanolamine (TEOA) and methanol. Mechanistic
      studies on the role of various sacrificial reagents in photocatalytic H2
      generation demonstrate that irreversible photodegradation of TEA into
      diethylamine and acetaldehyde via monoelectronic oxidation contributes to the
      improved H2 yield. Similarly, TEOA is oxidized to diethanolamine and
      glycolaldehyde, whereas methanol is unable to quickly capture the photoinduced
      holes and remains intact due to the low oxidation potential.

PMID- 29465983
TI  - Targeting the Proteostasis Network for Mycobacterial Drug Discovery.
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the
      world's deadliest infectious diseases and urgently requires new antibiotics to
      treat drug-resistant strains and to decrease the duration of therapy. During
      infection, Mtb encounters numerous stresses associated with host immunity,
      including hypoxia, reactive oxygen and nitrogen species, mild acidity, nutrient
      starvation, and metal sequestration and intoxication. The Mtb proteostasis
      network, composed of chaperones, proteases, and a eukaryotic-like proteasome,
      provides protection from stresses and chemistries of host immunity by maintaining
      the integrity of the mycobacterial proteome. In this Review, we explore the
      proteostasis network as a noncanonical target for antibacterial drug discovery.

PMID- 29465988
TI  - Light-Switchable Ion Channels and Receptors for Optogenetic Interrogation of
      Neuronal Signaling.
AB  - Optogenetics is an emerging technique that enables precise and specific control
      of biological activities in defined space and time. This technique employs
      naturally occurring or engineered light-responsive proteins to manipulate the
      physiological processes of the target cells. To better elucidate the molecular
      bases of neural functions, substantial efforts have been made to confer light
      sensitivity onto ion channels and neurotransmitter receptors that mediate
      signaling events within and between neurons. The chemical strategies for
      engineering light-switchable channels/receptors and the neuronal implementation
      of these tools are discussed.

PMID- 29465989
TI  - Correction to Design Rule for Improved Open-Circuit Voltage in Binary and Ternary
      Organic Solar Cells.

PMID- 29465991
TI  - Comment on "Differential Health Effects of Constant and Intermittent Exposure to
      Formaldehyde in Mice: Implications for Building Ventilation Strategies".

PMID- 29465990
TI  - Excitation-Wavelength-Dependent Photocycle Initiation Dynamics Resolve
      Heterogeneity in the Photoactive Yellow Protein from Halorhodospira halophila.
AB  - Photoactive yellow proteins (PYPs) make up a diverse class of blue-light
      absorbing bacterial photoreceptors. Electronic excitation of the p-coumaric acid
      chromophore covalently bound within PYP results in triphasic quenching kinetics;
      however, the molecular basis of this behavior remains unresolved. Here we explore
      this question by examining the excitation-wavelength dependence of the
      photodynamics of the PYP from Halorhodospira halophila via a combined
      experimental and computational approach. The fluorescence quantum yield, steady
      state fluorescence emission maximum, and cryotrapping spectra are demonstrated to
      depend on excitation wavelength. We also compare the femtosecond photodynamics in
      PYP at two excitation wavelengths (435 and 475 nm) with a dual-excitation
      wavelength-interleaved pump-probe technique. Multicompartment global analysis of
      these data demonstrates that the excited-state photochemistry of PYP depends
      subtly, but convincingly, on excitation wavelength with similar kinetics with
      distinctly different spectral features, including a shifted ground-state beach
      and altered stimulated emission oscillator strengths and peak positions. Three
      models involving multiple excited states, vibrationally enhanced barrier
      crossing, and inhomogeneity are proposed to interpret the observed excitation
      wavelength dependence of the data. Conformational heterogeneity was identified as
      the most probable model, which was supported with molecular mechanics simulations
      that identified two levels of inhomogeneity involving the orientation of the R52
      residue and different hydrogen bonding networks with the p-coumaric acid
      chromophore. Quantum calculations were used to confirm that these inhomogeneities
      track to altered spectral properties consistent with the experimental results.

PMID- 29465992
TI  - Local Structure of Zr(OH)4 and the Effect of Calcination Temperature from X-ray
      Pair Distribution Function Analysis.
AB  - Analysis of X-ray pair distribution function data has provided a detailed picture
      of the local structure of amorphous Zr(OH)4 and its thermal decomposition into
      ZrO2. In the untreated phase, the Zr atoms tend to be coordinated by six or seven
      oxygen atoms. The Zr centered polyhedra connect to each other primarily by
      sharing edges, but also with a significant amount of corner sharing, to form two
      dimensional sheets in which the Zr are connected to an average of about five
      other Zr. This local structure is related to the structure of monoclinic ZrO2 and
      can be derived from it by removing certain Zr neighbors to form sheets and reduce
      the corner to edge sharing ratio. The maximum correlation length in Zr(OH)4 is
      about 12 A. Heating up to 125  degrees C results in significant water loss but
      does not alter the network of Zr and bridging O atoms. Additional water loss
      caused by heating to 250  degrees C triggers a reorganization into a new type of
      amorphous phase with a three-dimensional network and a greater number of Zr-Zr
      neighbors. Further heating to 330  degrees C causes crystallization into a
      mixture of tetragonal and monoclinic ZrO2, with the minor tetragonal phase having
      a smaller average domain size. The tetragonal component vanishes by 900  degrees
      C.

PMID- 29465993
TI  - Series of Highly Stable Lanthanide-Organic Frameworks Constructed by a
      Bifunctional Linker: Synthesis, Crystal Structures, and Magnetic and Luminescence
      Properties.
AB  - By utilizing a preselected functional ligand produced by 1 H-imidazole-4,5
      dicarboxylic acid, three isostructural lanthanide coordination polymers (CPs),
      denoted as {[Ln2(OH)2(L)2].(DMF).(H2O)4} n (Ln = Gd (1), Eu (2), Dy (3); L = 1-(4
      carboxybenzyl)imidazole-4-carboxylic acid), containing a 1D infinite [Ln4(OH)4]
      subchain have been successfully constructed. The highly connected mode between
      the multifunctional ligand and 1D building units is responsible for the
      exceptional chemical stability of three lanthanide CPs. In addition, a study of
      the magnetic properties reveals that 1 displays a large magnetic entropy change (
      Delta Sm = 30.33 J kg-1 K-1 with T = 2 K and Delta H = 7 T). Furthermore, genetic
      algorithm and quantum Monte Carlo methods were combined to simulate the magnetic
      coupling parameters of compound 1, shedding light on the effect of linking
      bridges on magnetic propagation. 2 shows intense luminescence in the range of 350
      710 nm. Comparably, magnetic studies of 3 reveal the existence of a metamagnetic
      transformation from an antiferromagnetic interaction to a ferromagnetic
      interaction along with a decrease in temperature. Through fitting of the results
      of HF-EPR measurements, a component of the g tensor is obtained, g|| = 16.4(5),
      indicating the large anisotropy of 3.

PMID- 29465994
TI  - Orbital Molecules in the New Spinel GaV2O4.
AB  - The structures and properties of vanadium oxides are often related to the
      formation of molecule-like clusters of vanadium cations through direct V-V
      bonding. GaV2O4, a new vanadium spinel, was synthesized. Powder diffraction and X
      ray total scattering studies, complemented by magnetization and resistivity
      measurements, reveal that the low-temperature phase of this material is
      structurally distorted and features ordered pairs of three- and four-atom
      vanadium clusters. These clusters persist into a disordered cubic phase above the
      charge-ordering transition at TCO = 415 K. Furthermore, quasi-elastic neutron
      scattering indicates that the disordered clusters remain well-defined and static
      to 1100 K.

PMID- 29465995
TI  - Natural Porphyrins Accelerating the Phototransformation of Benzo[a]pyrene in
      Water.
AB  - Phototransformation is one of the most important transformation pathways of
      organic contaminants in the water environment. However, how active compounds
      enable and accelerate the phototransformation of organic pollutants remains to be
      elucidated. In this study, the phototransformation of benzo[a]pyrene (BaP, the
      first class "human carcinogens") by various natural porphyrins under solar
      irradiation was investigated, including chlorophyll a, sodium copper
      chlorophyllin, hematin, cobalamin, and pheophorbide a. Transformation efficiency
      of BaP varied considerably with chemical stabilities of the porphyrins.
      Porphyrins with a lower stability displayed higher BaP transformation
      efficiencies. BaP transformation had a significant positive correlation with the
      production of singlet oxygen. Identical phototransformation products of BaP were
      observed for all investigated porphyrins, and the main products were identified
      as BaP-quinones, including BaP-1,6-dione, BaP-3,6-dione, and BaP-6,12-dione. The
      mechanism of natural porphyrins accelerating the BaP phototransformation in water
      was proposed to proceed via the photocatalytic generation of singlet oxygen
      resulting in the transformation of BaP to quinones.

PMID- 29465996
TI  - Palladium and Lewis-Acid-Catalyzed Intramolecular Aminocyanation of Alkenes:
      Scope, Mechanism, and Stereoselective Alkene Difunctionalizations.
AB  - An expansion of methodologies aimed at the formation of versatile organonitriles,
      via the intramolecular aminocyanation of unactivated alkenes, is herein reported.
      Importantly, the need for a rigid tether in these reactions has been obviated.
      The ease-of-synthesis and viability of substrates bearing flexible backbones has
      permitted for diastereoselective variants as well. We demonstrated the utility of
      this methodology with the formation of pyrrolidones, piperidinones,
      isoindolinones, and sultams. Furthermore, subsequent transformation of these
      motifs into medicinally relevant molecules is also demonstrated. A double
      crossover 13C-labeling experiment is consistent with a fully intramolecular
      cyclization mechanism. Deuterium labeling experiments support a mechanism
      involving syn-addition across the alkene.

PMID- 29465997
TI  - Enhanced Methane Production from Food Waste Using Cysteine To Increase
      Biotransformation of l-Monosaccharide, Volatile Fatty Acids, and Biohydrogen.
AB  - The enhancement of two-stage anaerobic digestion of polysaccharide-enriched food
      waste by the addition of cysteine-an oxygen scavenger, electron mediator, and
      nitrogen source-to the acidification stage was reported. It was found that in the
      acidification stage the accumulation of volatile fatty acids (VFA), which mainly
      consisted of acetate, butyrate, and propionate, was increased by 49.3% at a
      cysteine dosage of 50 mg/L. Although some cysteine was biodegraded in the
      acidification stage, the VFA derived from cysteine was negligible. In the
      methanogenesis stage, the biotransformations of both VFA and biohydrogen to
      methane were enhanced, and the methane yield was improved by 43.9%. The
      mechanisms study showed that both d-glucose and l-glucose (the model
      monosaccharides) were detectable in the hydrolysis product, and the addition of
      cysteine remarkably increased the acidification of l-glucose, especially acetic
      acid and hydrogen generation, due to key enzymes involved in l-glucose metabolism
      being enhanced. Cysteine also improved the activity of homoacetogens by 34.8% and
      hydrogenotrophic methanogens by 54%, which might be due to the electron transfer
      process being accelerated. This study provided an alternative method to improve
      anaerobic digestion performance and energy recovery from food waste.

PMID- 29465998
TI  - Diastereo- and Enantioselective Formal [3 + 2] Cycloaddition of Cyclopropyl
      Ketones and Alkenes via Ti-Catalyzed Radical Redox Relay.
AB  - We report a stereoselective formal [3 + 2] cycloaddition of cyclopropyl ketones
      and radical-acceptor alkenes to form polysubstituted cyclopentane derivatives.
      Catalyzed by a chiral Ti(salen) complex, the cycloaddition occurs via a radical
      redox-relay mechanism and constructs two C-C bonds and two contiguous stereogenic
      centers with generally excellent diastereo- and enantioselectivity.

PMID- 29465999
TI  - Efficient Method for Calculating Effective Core Potential Integrals.
AB  - Effective core potential (ECP) integrals are among the most difficult one
      electron integrals to calculate due to the projection operators. The radial part
      of these operators may include r0, r-1, and r-2 terms. For the r0 terms, we
      exploit a simple analytic expression for the fundamental projected integral to
      derive new recurrence relations and upper bounds for ECP integrals. For the r-1
      and r-2 terms, we present a reconstruction method that replaces these terms by a
      sum of r0 terms and show that the resulting errors are chemically insignificant
      for a range of molecular properties. The new algorithm is available in Q-Chem 5.0
      and is significantly faster than the ECP implementations in Q-Chem 4.4, GAMESS
      (US) and Dalton 2016.

PMID- 29466000
TI  - Python Cathelicidin CATHPb1 Protects against Multidrug-Resistant Staphylococcal
      Infections by Antimicrobial-Immunomodulatory Duality.
AB  - Multidrug-resistant Staphylococcus aureus, including MRSA (methicillin-resistant)
      and VRSA (vancomycin-resistant), causes serious healthcare-associated infections,
      even sepsis and death. Here, we identified six novel cathelicidins (CATHPb1-6)
      from Python bivittatu, and CATHPb1 displayed the best in vitro pharmacological
      and toxicological profile. We further show that CATHPb1 exhibited evident
      protection in mice MRSA/VRSA infection models, given either 24 h before or 4 h
      after infection. The protection was all effective through different
      administration routes, but was blocked by in vivo depletion of
      monocyte/macrophages or neutrophils. CATHPb1 can rapidly and massively modulate
      macrophages/monocytes and neutrophils trafficking to the infection site, and
      potentiate their bactericidal functions. Meanwhile, CATHPb1 remarkably augmented
      neutrophil-mediated bacteria killing by facilitating neutrophil extracellular
      traps (NETs) formation and preventing its degradation. Acting through MAPKs and
      NF-kappaB pathways, CATHPb1 selectively enhanced the levels of chemokines while
      reducing the production of pro-inflammatory cytokines without undesirable
      toxicities. The much improved serum half-life and stabilities confer CATHPb1 an
      excellent prospect to become a novel therapeutic agent against multidrug
      resistant staphylococcal infections.

PMID- 29466001
TI  - Introduction of Intrinsic Kinetics of Protein-Ligand Interactions and Their
      Implications for Drug Design.
AB  - Structure-kinetic relationship analyses and identification of dominating
      interactions for optimization of lead compounds should ideally be based on
      intrinsic rate constants instead of the more easily accessible observed kinetic
      constants, which also account for binding-linked reactions. The intrinsic rate
      constants for sulfonamide inhibitors and pharmacologically relevant isoforms of
      carbonic anhydrase were determined by a novel surface plasmon resonance (SPR)
      biosensor-based approach, using chemodynamic analysis of binding-linked pH
      dependent effects. The observed association rates ( kaobs) were pH-dependent and
      correlated with the fraction of deprotonated inhibitor and protonated zinc-bound
      water molecule. The intrinsic association rate constants ( kaintr) were pH
      independent and higher than kaobs. By contrast, the observed and intrinsic
      dissociation rate constants were identical and pH-independent, demonstrating that
      the observed association and dissociation mechanisms are inherently different. A
      model accounting for the differences between intrinsic and observed rate
      constants was developed, useful also for other interactions with binding-linked
      protonation reactions.

PMID- 29466002
TI  - Development of Potent Inhibitors of Receptor Tyrosine Kinases by Ligand-Based
      Drug Design and Target-Biased Phenotypic Screening.
AB  - Pyrazolopyrimidines with potent antiproliferative properties were developed by an
      adaptive strategy that applies ligand-based design and phenotypic screening
      iteratively and is informed by biochemical assays. To drive development toward
      specific oncopathways, compounds were tested against cancer cells that
      overexpress, or not, AXL kinase. Identified phenotypic hits were found to inhibit
      oncotargets AXL, RET, and FLT3. Subsequent optimization generated
      antiproliferative lead compounds with unique selectivity profiles, including
      selective AXL inhibitors and a highly potent inhibitor of FLT3.

PMID- 29466003
TI  - Electronic Structure and Bonding Situation in M2O2 (M = Be, Mg, Ca) Rhombic
      Clusters.
AB  - Quantum chemical calculations using ab initio methods at the CCSD(T) level and
      density functional theory have been carried out for the title molecules. The
      electronic structures of the molecules were analyzed with a variety of charge and
      energy decomposition methods. The equilibrium geometries of the M2O2 rhombic
      clusters exhibit very short distances between the transannular metal atoms M =
      Be, Mg, Ca. The calculated distances are close to standard values between double
      and triple bonds, but there are no chemical M-M bonds. The metal atoms M carry
      large positive partial charges, which are even bigger than in diatomic MO. The
      valence electrons of M are essentially shifted toward oxygen in M2O2, which makes
      it possible that there is practically no electronic charge in the region between
      the metal atoms. The bond dissociation energies for fragmentation of M2O2 into
      two metal oxides MO are very large. The metal-oxide bonds in the rhombic clusters
      are shorter and stronger than in diatomic MO. A detailed analysis of the
      electronic structure suggests that there is no significant direct M-M interaction
      in the M2O2 rhombic clusters, albeit weak three-center M-O-M bonding.

PMID- 29466004
TI  - Reaction Coordinate, Free Energy, and Rate of Intramolecular Proton Transfer in
      Human Carbonic Anhydrase II.
AB  - The role of structure and dynamics of an enzyme has been investigated at three
      different stages of its function including the chemical event it catalyzes. A one
      pot computational method has been designed for each of these stages on the basis
      of classical and/or quantum mechanical-molecular mechanical molecular dynamics
      and transition path sampling simulations. For a pair of initial and final states
      A and B separated by a high free-energy barrier, using a two-stage selection
      process, several collective variables (CVs) are identified that can delineate A
      and B. However, these CVs are found to exhibit strong cross-coupling over the
      transition paths. A set of mutually orthogonal order parameters is then derived
      from these CVs and an optimal reaction coordinate, r, determined applying half
      trajectory likelihood maximization along with a Bayesian information criterion.
      The transition paths are also used to project the multidimensional free energy
      surface and barrier crossing dynamics along r. The proposed scheme has been
      applied to the rate-determining intramolecular proton transfer reaction of the
      well-known enzyme human carbonic anhydrase II. The potential of mean force, F(
      r), in the absence of the chemical step is found to reproduce earlier results on
      the equilibrium population of two side-chain orientations of key residue His-64.
      Estimation of rate constants, k, from mean first passage times for the three
      different stages of catalysis shows that the rate-determining step of
      intramolecular proton transfer occurs with k ? 1.0 * 106 s-1, in close agreement
      with known experimental results.

PMID- 29466006
TI  - Quantum Stochastic Trajectories: The Fokker-Planck-Bohm Equation Driven by the
      Reduced Density Matrix.
AB  - The quantum molecular trajectory is the deterministic trajectory, arising from
      the Bohm theory, that describes the instantaneous positions of the nuclei of
      molecules by assuring the agreement with the predictions of quantum mechanics.
      Therefore, it provides the suitable framework for representing the geometry and
      the motions of molecules without neglecting their quantum nature. However, the
      quantum molecular trajectory is extremely demanding from the computational point
      of view, and this strongly limits its applications. To overcome such a drawback,
      we derive a stochastic representation of the quantum molecular trajectory,
      through projection operator techniques, for the degrees of freedom of an open
      quantum system. The resulting Fokker-Planck operator is parametrically dependent
      upon the reduced density matrix of the open system. Because of the pilot role
      played by the reduced density matrix, this stochastic approach is able to
      represent accurately the main features of the open system motions both at
      equilibrium and out of equilibrium with the environment. To verify this
      procedure, the predictions of the stochastic and deterministic representation are
      compared for a model system of six interacting harmonic oscillators, where one
      oscillator is taken as the open quantum system of interest. The undeniable
      advantage of the stochastic approach is that of providing a simplified and self
      contained representation of the dynamics of the open system coordinates.
      Furthermore, it can be employed to study the out of equilibrium dynamics and the
      relaxation of quantum molecular motions during photoinduced processes, like
      photoinduced conformational changes and proton transfers.

PMID- 29466005
TI  - Optimization of Metabolic and Renal Clearance in a Series of Indole Acid Direct
      Activators of 5'-Adenosine Monophosphate-Activated Protein Kinase (AMPK).
AB  - Optimization of the pharmacokinetic (PK) properties of a series of activators of
      adenosine monophosphate-activated protein kinase (AMPK) is described. Derivatives
      of the previously described 5-aryl-indole-3-carboxylic acid clinical candidate
      (1) were examined with the goal of reducing glucuronidation rate and minimizing
      renal excretion. Compounds 10 (PF-06679142) and 14 (PF-06685249) exhibited robust
      activation of AMPK in rat kidneys as well as desirable oral absorption, low
      plasma clearance, and negligible renal clearance in preclinical species. A
      correlation of in vivo renal clearance in rats with in vitro uptake by human and
      rat renal organic anion transporters (human OAT/rat Oat) was identified.
      Variation of polar functional groups was critical to mitigate active renal
      clearance mediated by the Oat3 transporter. Modification of either the 6
      chloroindole core to a 4,6-difluoroindole or the 5-phenyl substituent to a
      substituted 5-(3-pyridyl) group provided improved metabolic stability while
      minimizing propensity for active transport by OAT3.

PMID- 29466007
TI  - Steric Crowding in Tetrel Bonds.
AB  - The tetravalent character of tetrel atoms leaves only limited room for an
      incoming nucleophile to approach and engage in a noncovalent bond with a tetrel
      atom. Any such approach can only occur at the expense of internal geometric
      distortions. The balance between attractive forces and repulsive steric crowding
      was studied for a series of Lewis acids of the type FTR3 (T = Si, Ge, Sn, Pb)
      which were allowed to interact with various bases. The strength and other
      properties of the tetrel bond are examined as the R groups are made progressively
      larger, varying from H and CH3 to isopropyl and tert-butyl, which induce steric
      crowding with the incoming base. The effects of crowding which impede the bond
      can be offset by enlarging the T atom, by adding electron-withdrawing
      substituents to the Lewis acid, or by considering stronger bases such as anions.
      The tetrel bond energies reach up to 10 kcal/mol for a pair of neutral molecules
      with no electron-withdrawing substituents on the Lewis acid. Adding -CF3
      substituents grows the interaction energy to as high as 35 kcal/mol, and a
      further increment occurs for an anionic base, taking the maximum up to 54
      kcal/mol.

PMID- 29466008
TI  - Raman Microscopy Insights on the Out-of-Plane Electrical Transport of Carbon
      Nanotube-Doped PEDOT:PSS Electrodes for Solar Cell Applications.
AB  - In the present report, we focused on the study of the out-of-plane electrical
      transport of multiwalled carbon nanotube (MWCNT)-doped poly(3,4
      ethylenedioxythiophene):poly(styrene sulfonate) composites (PEDOT:PSS-MWCNTs) as
      electrodes for solar cell applications. The out-of-plane direct current and
      alternating current electrical transport, rarely studied but not less relevant,
      was additionally supported with in-plane and out-of-plane confocal Raman
      microscopy and grazing incidence small-angle X-ray scattering characterizations.
      The main relevance of our study is the monitoring of the polymer structure all
      across the polymeric film by using confocal Raman spectroscopy and its
      correlation with electrical transport. Modifications in the PEDOT benzenoid and
      quinoid conformations were observed in the vicinities of MWCNTs, and the
      enrichment of PSS at the indium tin oxide electrode interface was also evidenced.
      In consequence, the low MWCNT loadings into PEDOT:PSS lead to an increase of the
      out-of-plane conductivity, but the heavier MWCNT loadings lead to a drastic
      decrease. The tuning of the doping level of these polymer composites and the
      understanding of the interface structure are crucial to fabricate electrodes with
      higher out-of-plane conductivities for organic solar cell applications.

PMID- 29466009
TI  - Interpreting Quasi-Thermal Effects in Ultrafast Spectroscopy of Hydrogen-Bonded
      Systems.
AB  - Vibrational excitation of molecules in the condensed phase relaxes through
      vibrational modes of decreasing energy to ultimately generate an equilibrium
      state in which the energy is distributed among low-frequency modes. In ultrafast
      vibrational spectroscopy, changes in the vibrational features of hydrogen-bonded
      NH and OH stretch modes are typically observed to persist long after these high
      frequency vibrations have relaxed. Due to the resemblance to the spectral changes
      caused by heating the sample, these features are typically described as arising
      from a hot ground state. However, these spectral features appear on ultrafast
      time scales that are much too fast to result from a true thermal state, and
      significant differences between the thermal difference spectrum and the induced
      quasi-thermal changes in ultrafast spectroscopy are often observed. Here, we
      examine and directly compare the thermal and quasi-thermal responses of the
      hydrogen-bonded homodimer of 7-azaindole with temperature-dependent FTIR
      spectroscopy and ultrafast mid-IR continuum spectroscopy. We find that the
      thermal difference spectra contain contributions from both dissociation of the
      hydrogen bonds and from frequency shifts due to changes in the thermal population
      of low-frequency modes. The transient spectra in ultrafast vibrational
      spectroscopy are also found to contain two contributions: initial frequency
      shifts over 2.3 +/- 0.11 ps associated with equilibration of the initial
      excitation, and frequency shifts associated with the excitation of several
      fingerprint modes, which decay over 21.8 +/- 0.11 ps, giving rise to a quasi
      thermal response caused by a distribution of fingerprint modes being excited
      within the sample ensemble. This resembles the thermal frequency shifts due to
      population changes of low-frequency modes, but not the overall thermal spectrum,
      which is dominated by features caused by dimer dissociation. These findings
      provide insight into the changes in the vibrational spectrum from different
      origins and are important for assigning, analyzing, and comparing features in
      thermal and ultrafast vibrational spectroscopy of hydrogen-bonded complexes.

PMID- 29466010
TI  - Dielectric Properties of a Protein Probed by Reversal of a Buried Ion Pair.
AB  - Thirty years ago, Hwang and Warshel suggested that a microenvironment
      preorganized to stabilize an ion pair would be incapable of reorganizing to
      stabilize the reverse ion pair. The implications were that (1) proteins have a
      limited capacity to reorganize, even under the influence of strong interactions,
      such as those present when ionizable groups are buried in the hydrophobic
      interior of a protein, and (2) the inability of proteins to tolerate the reversal
      of buried ion pairs demonstrates the limitations inherent to continuum
      electrostatic models of proteins. Previously we showed that when buried
      individually in the interior of staphylococcal nuclease, Glu23 and Lys36 have p
      Ka values near pH 7, but when buried simultaneously, they establish a strong
      interaction of ~5 kcal/mol and have p Ka values shifted toward more normal
      values. Here, using equilibrium thermodynamic measurements, crystal structures,
      and NMR spectroscopy experiments, we show that although the reversed, individual
      substitutions-Lys23 and Glu36-also have p Ka values near 7, when buried together,
      they neither establish a strong interaction nor promote reorganization of their
      microenvironment. These experiments both confirm Warshel's original hypothesis
      and expand it by showing that it applies to reorganization, as demonstrated by
      our artificial ion pairs, as well as to preorganization as is commonly argued for
      motifs that stabilize naturally occurring ion pairs in polar microenvironments.
      These data constitute a challenging benchmark useful to test the ability of
      structure-based algorithms to reproduce the compensation between self-energy,
      Coulomb and polar interactions in hydrophobic environments of proteins.

PMID- 29466011
TI  - Cobalt-Catalyzed, N-H Imine-Directed Hydroarylation of Styrenes.
AB  - A cobalt-catalyzed, N-H imine-directed hydroarylation reaction of styrenes is
      reported. A variety of diaryl and aryl alkyl N-H imines participated in the
      reaction to afford the corresponding branched adducts in good yield and
      regioselectivity. Interestingly, unsymmetrical diaryl imines with modest
      electronic biases reacted regioselectively at one of the aryl rings. Furthermore,
      the branched selectivity was reversed for substrates bearing a secondary
      directing group or a bulky pivaloyl N-H imine.

PMID- 29466012
TI  - Primary and Higher Order Structure of the Reaction Center from the Purple
      Phototrophic Bacterium Blastochloris viridis: A Test for Native Mass
      Spectrometry.
AB  - The reaction center (RC) from the phototrophic bacterium Blastochloris viridis
      was the first integral membrane protein complex to have its structure determined
      by X-ray crystallography and has been studied extensively since then. It is
      composed of four protein subunits, H, M, L, and C, as well as cofactors,
      including bacteriopheophytin (BPh), bacteriochlorophyll (BCh), menaquinone,
      ubiquinone, heme, carotenoid, and Fe. In this study, we utilized mass
      spectrometry-based proteomics to study this protein complex via bottom-up
      sequencing, intact protein mass analysis, and native MS ligand-binding analysis.
      Its primary structure shows a series of mutations, including an unusual
      alteration and extension on the C-terminus of the M-subunit. In terms of
      quaternary structure, proteins such as this containing many cofactors serve to
      test the ability to introduce native-state protein assemblies into the gas phase
      because the cofactors will not be retained if the quaternary structure is
      seriously perturbed. Furthermore, this specific RC, under native MS, exhibits a
      strong ability not only to bind the special pair but also to preserve the two
      peripheral BCh's.

PMID- 29466013
TI  - Evidence of a Transition Layer between the Free Surface and the Bulk.
AB  - The free surface, a very thin layer at the interface between polymer and air, is
      considered the main source of the perturbations in the properties of ultrathin
      polymer films, i.e., nanoconfinement effects. The structural relaxation of such a
      layer is decoupled from the molecular dynamics of the bulk. The free surface is,
      in fact, able to stay liquid even below the temperature where the polymer resides
      in the glassy state. Importantly, this surface layer is expected to have a very
      sharp interface with the underlying bulk. Here, by analyzing the penetration of n
      hexane into polystyrene films, we report on the existence of a transition region,
      not observed by previous investigations, extending for 12 nm below the free
      surface. The presence of such a layer permits reconciling the behavior of
      interfacial layers with current models and has profound implications on the
      performance of ultrathin membranes. We show that the expected increase in the
      flux of the permeating species is actually overruled by nanoconfinement.

PMID- 29466014
TI  - Impact of Polyelectrolyte Multilayers on the Ionic Current Rectification of
      Conical Nanopores.
AB  - Single conical nanopores were functionalised layer by layer with weak
      polyelectrolytes. We studied their influence on the ionic diode properties We
      have considered different couples of polyelectrolytes: poly-l-lysine/poly(acrylic
      acid) and poly(ethyleneimine)/poly(acrylic acid) as well as the influence of
      cross-linking. The results show that the nanopores decorated with
      poly(ethyleneimine)/poly(acrylic acid) exhibit an interesting behavior. Indeed,
      at pH 3, the nanopore is open only at the low salt concentration, while at pH 7,
      it is already open. The nanopores functionalized with poly-l-lysine/poly(acrylic
      acid) do not show an inversion of ionic transport properties with the pH as
      expected. After cross-linked to prevent large conformational changes, the ionic
      diode properties are dependent on the pH.

PMID- 29466015
TI  - Mating-Induced Differential Peptidomics of Neuropeptides and Protein Hormones in
      Agrotis ipsilon Moths.
AB  - In many insects, mating induces drastic changes in male and female responses to
      sex pheromones or host-plant odors. In the male moth Agrotis ipsilon, mating
      induces a transient inhibition of behavioral and neuronal responses to the female
      sex pheromone. As neuropeptides and peptide hormones regulate most behavioral
      processes, we hypothesize that they could be involved in this mating-dependent
      olfactory plasticity. Here we used next-generation RNA sequencing and a
      combination of liquid chromatography, matrix assisted laser desorption ionization
      time-of-flight (MALDI-TOF) mass spectrometry, and direct tissue profiling to
      analyze the transcriptome and peptidome of different brain compartments in virgin
      and mated males and females of A. ipsilon. We identified 37 transcripts encoding
      putative neuropeptide precursors and 54 putative bioactive neuropeptides from 23
      neuropeptide precursors (70 sequences in total, 25 neuropeptide precursors) in
      different areas of the central nervous system including the antennal lobes, the
      gnathal ganglion, and the corpora cardiaca-corpora allata complex. Comparisons
      between virgin and mated males and females revealed tissue-specific differences
      in peptide composition between sexes and according to physiological state. Mated
      males showed postmating differences in neuropeptide occurrence, which could
      participate in the mating-induced olfactory plasticity.

PMID- 29466016
TI  - Iridium- and Rhodium-Catalyzed Directed C-H Heteroarylation of Benzaldehydes with
      Benziodoxolone Hypervalent Iodine Reagents.
AB  - The C-H heteroarylation of benzaldehydes with indoles and pyrroles was realized
      using the benziodoxolone hypervalent iodine reagents indole- and pyrroleBX.
      Functionalization of the aldehyde C-H bond using either an o-hydroxy or amino
      directing group and catalyzed by an iridium or a rhodium complex allowed the
      synthesis of salicyloylindoles and (2-sulfonamino)benzoylindoles, respectively,
      with good to excellent yields (74-98%). This new transformation could be carried
      out under mild conditions (rt to 40  degrees C) and tolerated a broad range of
      functionalities, such as ethers, halogens, carbonyls, or nitro groups.

PMID- 29466017
TI  - Aza-Riley Oxidation of Ugi-Azide and Ugi-3CR Products toward Vicinal Tricarbonyl
      Amides: Two-Step MCR-Oxidation Methodology Accessing Functionalized alpha,beta
      Diketoamides and alpha,beta-Diketotetrazoles.
AB  - Direct oxidative deamination of glyoxal-derived Ugi-azide and Ugi three-component
      reaction products readily affords vicinal tricarbonyls (alpha,beta-diketoamides)
      and alpha,beta-diketotetrazoles with two diversity elements. This significant
      extension of our previously described multicomponent reaction-oxidative
      deamination methodology is proposed to proceed through a mechanistically distinct
      SeO2-mediated C-N oxidation derived from an active enol of alpha-amino-beta
      ketone systems, effectively an aza-Riley oxidation. This methodology accesses
      diverse VTC systems from prototypical amines, glyoxaldehydes, and isocyanide
      building blocks in a mere two steps.

PMID- 29466018
TI  - Differences in learning retention when teaching a manual motor skill with a
      visual vs written instructional aide.
AB  - OBJECTIVE:: This study aimed to determine if a written or visual teaching aid
      influenced learning retention when teaching a manual motor skill. METHODS::
      Seventy chiropractic students who had completed an upper cervical specific
      chiropractic technique course were evaluated for technique-specific recall before
      and after a review using either a visual teaching aid or a written guide. Two
      randomized groups reviewed original course-written guides ( n = 33) or new visual
      teaching aids ( n = 37). Repeated-measures analysis of variance and post hoc t
      tests compared group differences in reevaluation scores. RESULTS:: Performance of
      both groups improved postintervention ( F[1, 68] = 182.56, p < .001). However,
      the visual teaching aid group improved more than the written guide group ( F[1,
      68] = 4.66, p = .03). The visual teaching aid group percentage score improved by
      24.4% (SD +/- 12.3%, p < .01); the written guide group improved by 17.7% (SD +/-
      13.7%; p < .01). CONCLUSION:: The mean learning retention improved in both the
      visual and the written teaching guide groups, but there was greater improvement
      in the visual aid group. This study suggests that visual teaching aids may be
      more useful than written guides when students attempt to recall information
      related to learning a manual motor skill.

PMID- 29466019
TI  - Video Analysis of Anterior Cruciate Ligament Tears in Professional American
      Football Athletes.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) injuries are prevalent in contact
      sports that feature cutting and pivoting, such as American football. These
      injuries typically require surgical treatment, can result in significant missed
      time from competition, and may have deleterious long-term effects on an athlete's
      playing career and health. While the majority of ACL tears in other sports have
      been shown to occur from a noncontact mechanism, it stands to reason that a
      significant number of ACL tears in American football would occur after contact,
      given the nature of the sport. Hypothesis/Purpose: The purpose was to describe
      the mechanism, playing situation, and lower extremity limb position associated
      with ACL injuries in professional American football players through video
      analysis to test the hypothesis that a majority of injuries occur via a contact
      mechanism. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A
      retrospective cohort of National Football League (NFL) players with ACL injuries
      from 3 consecutive seasons (2013-2016) was populated by searching publicly
      available online databases and other traditional media sources. Of 156 ACL
      injuries identified, 77 occurred during the regular season and playoffs, with
      video analysis available for 69 injuries. The video of each injury was
      independently viewed by 2 reviewers to determine the nature of the injury (ie,
      whether it occurred via a noncontact mechanism), the position of the lower
      extremity, and the football activity at the time of injury. Playing surface,
      player position, and time that the injury occurred were also recorded. RESULTS:
      Contrary to our hypothesis, the majority of ACL injuries occurred via a
      noncontact mechanism (50 of 69, 72.5%), with the exception of injury to offensive
      linemen, who had a noncontact mechanism in only 20% of injuries. For noncontact
      injuries, the most common football activity at the time of injury was
      pivoting/cutting, and the most common position of the injured extremity included
      hip abduction/flexion, early knee flexion/abduction, and foot abduction/external
      rotation. There was no association between injury mechanism and time of injury or
      playing surface in this cohort. CONCLUSION: In this study of players in the NFL,
      the majority of ACL tears involved a noncontact mechanism, with the lower
      extremity exhibiting a dynamic valgus moment at the knee. These findings suggest
      that ACL injury prevention programs may reduce the risk of noncontact ACL tears
      in American football players.

PMID- 29466021
TI  - Assessment of Performance Carryover Effects Due to Successive Exposure to
      Different Lateral Camera Rotations in a Laparoscopic Training Environment.
AB  - Objective The aim of this study was to assess performance carryover effects
      associated with different successive lateral camera rotations in the laparoscopic
      training environment. Background Laparoscopy requires surgeons to adapt to
      disruptions of visuomotor mapping. A gradual adaptation process is hypothesized
      to be effective up to a given rotation threshold; this threshold may have
      performance implications for successive exposure to different lateral camera
      rotations. Method Two experiments utilized a laparoscopic training task.
      Experiment 1 exposed novices to a subsequent rotation that was either 45 degrees 
      larger than one of the initial rotations of 45 degrees , 75 degrees , 105 degrees
      , and 135 degrees  or 45 degrees  smaller than one of the initial rotations of 90
      degrees , 120 degrees , 150 degrees , and 180 degrees . Experiment 2 exposed
      novices to either stepwise increasing rotations (0 degrees  to 180 degrees ) or
      stepwise decreasing rotations (180 degrees  to 0 degrees ). Results Regarding
      Experiment 1, performance generally improved for subsequent rotations that were
      45 degrees  larger than the initial rotation, except for one condition (initial
      rotation, 105 degrees ; subsequent rotation, 150 degrees ). Performance generally
      improved for subsequent rotations that were 45 degrees  smaller than the initial
      rotation, except for one condition (initial rotation, 120 degrees ; subsequent
      rotation, 75 degrees ). Experiment 2 indicated worst performance at 120 degrees 
      for the increasing and decreasing conditions. This finding suggests an identical
      threshold for increasing and decreasing rotations, which is inconsistent with
      Experiment 1 results. Conclusion Improved performance due to carryover effects
      from successive exposure to lateral camera rotations in the laparoscopic training
      environment is contingent on the specific camera rotations. Application
      Supplementary laparoscopic training might be needed for surgeries that entail
      certain successive lateral camera rotations.

PMID- 29466022
TI  - From Liguria HIV Web to Liguria Infectious Diseases Network: How a Digital
      Platform Improved Doctors' Work and Patients' Care.

PMID- 29466024
TI  - Sexual Self-Efficacy and Gender: A Review of Condom Use and Sexual Negotiation
      Among Young Men and Women in Sub-Saharan Africa.
AB  - Sexual self-efficacy (SSE), one's perceived control of or confidence in the
      ability to perform a given sexual outcome, predicts sexual behavior; however,
      important questions remain regarding whether gender modifies observed
      associations. In a comprehensive review of peer-reviewed HIV-prevention
      literature focusing on youth (ages 10 to 25) in sub-Saharan Africa, we measured
      and assessed the influence of SSE on condom use and sexual refusal, overall and
      by gender. Our results, after reviewing 63 publications, show that SSE is
      inconsistently measured. Most studies measured condom use self-efficacy (CUSE)
      (96.8%) and/or sexual refusal self-efficacy (SRSE) (63.5%). On average, young men
      had higher CUSE than young women, while young women had higher SRSE than young
      men. While cross-sectional studies reported an association between high SSE and
      sexual behaviors, this association was not observed in interventions,
      particularly among young women who face a disproportionate risk of HIV
      acquisition. In all, 25% of intervention studies demonstrated that fostering CUSE
      increased condom use among young men only, and one of two studies demonstrated
      that higher SRSE led to reduced frequency of sexual activity for both men and
      women. Future research and HIV-prevention interventions must be gender targeted,
      consider improving CUSE for young men, and move beyond limited individual-level
      sexual behavior change frameworks.

PMID- 29466026
TI  - Opposition-Based Memetic Algorithm and Hybrid Approach for Sorting Permutations
      by Reversals.
AB  - Sorting unsigned permutations by reversals is a difficult problem; indeed, it was
      proved to be NP-hard by Caprara (1997). Because of its high complexity, many
      approximation algorithms to compute the minimal reversal distance were proposed
      until reaching the nowadays best-known theoretical ratio of 1.375. In this
      article, two memetic algorithms to compute the reversal distance are proposed.
      The first one uses the technique of opposition-based learning leading to an
      opposition-based memetic algorithm; the second one improves the previous
      algorithm by applying the heuristic of two breakpoint elimination leading to a
      hybrid approach. Several experiments were performed with one-hundred randomly
      generated permutations, single benchmark permutations, and biological
      permutations. Results of the experiments showed that the proposed OBMA and Hybrid
      OBMA algorithms achieve the best results for practical cases, that is, for
      permutations of length up to 120. Also, Hybrid-OBMA showed to improve the results
      of OBMA for permutations greater than or equal to 60. The applicability of our
      proposed algorithms was checked processing permutations based on biological data,
      in which case OBMA gave the best average results for all instances.

PMID- 29466027
TI  - Effect of Cold-Water Immersion on Handgrip Performance in Rock Climbers.
AB  - PURPOSE: To determine the effect of 2 cold-water-immersion (CWI) temperatures (15
      degrees C and 8 degrees C) on repeat handgrip performance to failure. METHODS: A
      total of 32 participants completed 3 intermittent trials to failure on a climbing
      specific handgrip dynamometer on 3 laboratory visits. For each visit, a different
      recovery strategy was employed: passive (PAS) recovery, CWI at 8 degrees C (CW8),
      or CWI at 15 degrees C (CW15). The force time integral (FTI: time of contraction
      multiplied by the force of contraction) was determined to assess handgrip
      performance. RESULTS: There was no significant difference between recovery
      strategies at the end of trial 1. In response to the PAS recovery strategy, there
      were 10% and 22% decreases in FTI in the second and third trials, respectively.
      The PAS recovery-strategy FTI values were lower than both CWI strategies for
      trials 2 and 3 (P < .05). FTI increased in the second trial (?32% and ?38%; P <
      .05) for both immersion strategies (CW8 and CW15, respectively) compared with
      trial 1. During the third trial, FTI was significantly higher for CW15 than CW8
      (?27% and ?4% with respect to baseline trial; P < .05). CONCLUSIONS: The results
      suggest that CWI has potential performance advantages over PAS recovery for rock
      climbing. The data show that in events where multiple recoveries are required, 15
      degrees C CWI may be more beneficial for climbers than 8 degrees C CWI. Future
      research should focus on the optimization of protocols for sport performance.

PMID- 29466033
TI  - A New Era of Cancer Biotherapy and Radiopharmaceuticals.

PMID- 29466028
TI  - Analysis of the Impact of Common Polymorphisms of the FTO and MC4R Genes with the
      Risk of Severe Obesity in Saudi Arabian Population.
AB  - BACKGROUND: Obesity has reached epidemic proportions worldwide resulting in a
      serious public health problem. In Saudi Arabia, 28.7% of the population is obese
      due largely to the adoption of western dietary patterns over the last decade. The
      fat-mass and obesity associated (FTO) and melanocortin-4 receptor (MC4R) genes
      are ubiquitously expressed in the brain and pancreatic islets, and are the main
      link between the central nervous system and energy homeostasis based on food
      intake and energy expenditure. Genetic variants in the FTO and MC4R genes have
      been strongly associated with an increased obesity risk. AIM: To identify novel
      mutations in the MC4R gene and to perform correlation analyses of the known
      variants rs9939609 and rs1421085 in the FTO gene and rs17782313 near the MC4R
      gene in an obese Saudi population. MATERIALS AND METHODS: A total of 136 obese
      patients and 104 healthy controls from King Fahd Hospital, Al-Khobar, were
      genotyped for single-nucleotide polymorphisms within or near the FTO and MC4R
      genes using the TaqMan assay. Leptin levels were determined by enzyme-linked
      immunosorbent assay. Targeted sequencing of MC4R exon was done by Sanger
      sequencing method. RESULTS: The study included 58 obese males and 78 obese
      females with a mean age of 39.78 +/- 12.77 years and a mean body mass index (BMI)
      of 42.65 +/- 9.03 kg/m2. A significant increase in the levels of leptin and
      triglycerides was associated with an increase of BMI. Other factors such as
      lactate dehydrogenase, gamma-glutamyltransferase, and high-density lipoprotein
      were also significantly higher in the severely obese cohort. The FTO
      polymorphisms were associated with a significantly increased risk for obesity and
      in BMI-stratified cohort, rs9939609 (T/A: odds ratio [OR] = 1.73, p = 0.007) and
      rs1421085 (T/C: OR = 1.56, p = 0.03) showed even stronger association. Genotyping
      for the near MC4R polymorphism, rs17782313 revealed an association with
      moderately obese patients (T/C: OR = 1.73, p = 0.038). CONCLUSION: The studied
      FTO gene polymorphisms were found to be significantly associated with increased
      BMI and were highly significantly associated with severe obesity. These FTO gene
      polymorphisms combined with a high-fat diet appear to promote early-onset obesity
      in the Saudi population. FTO polymorphisms appear to be universally associated
      with the risk of obesity, and further investigation into this genetic locus may
      provide clues for potential therapeutic targets.

PMID- 29466034
TI  - Astragalus Saponins and Liposome Constitute an Efficacious Adjuvant Formulation
      for Cancer Vaccines.
AB  - Cancer vaccines mostly aim to induce cytotoxic T lymphocytes (CTLs) against
      tumors. An appropriate adjuvant is of fundamental importance for inducing
      cellular immune response. Since the antigen in particulate form is substantially
      more immunogenic than soluble form antigen, it is beneficial to interact with
      antigen-presenting cells membrane to induce robust CD8+ T cell activation
      following vaccination. Based on previous research, we designed an adjuvant
      formulation by combining Astragalus saponins, cholesterol, and liposome to
      incorporate antigen into a particulate delivery system, so as to enhance cellular
      immune response. Meanwhile, angiogenesis contributes to tumor growth and
      metastasis, and basic fibroblast growth factor (bFGF) is involved in tumor
      angiogenesis. Therefore, using lipo-saponins adjuvant formulation and a human
      recombinant bFGF antigen protein, we tried to induce bFGF-specific CTL response
      to inhibit tumor angiogenesis to achieve antitumor activity. After five
      immunizations, the lipo-saponins/bFGF complex elicited robust antibody response
      and markedly higher amount of interferon-gamma in BALB/c mice, resulting in
      superior antitumor activities. Decreased microvessel density in CD31
      immunohistochemistry and the lysis of vascular endothelial cells by the T
      lymphocytes from the immunized mice indicated that the immunity inhibited the
      angiogenesis of tumors and further led to the inhibition of tumors. Our data
      suggest that the approach to construct adjuvant formulation between liposome and
      Astragalus saponins appeared highly desirable, and that Astragalus saponins may
      be utilized as a valuable additive for enhancing the effectiveness of vaccines
      and stimulating an appropriate immune response that can benefit tumor therapy.

PMID- 29466035
TI  - Inhibition of STAT6/Anoctamin-1 Activation Suppresses Proliferation and Invasion
      of Gastric Cancer Cells.
AB  - BACKGROUND: Gastric carcinoma is the most popular cancer worldwide. Anoctamin-1
      is a calcium-activated channel and highly expressed in various tumors. A previous
      study indicated that suppressed Anoctamin-1 expression decreased cancer cell
      proliferation or migration. As a signal transduction and transcription activator,
      STAT6 is a novel agonist for Anoctamin-1 promoter. However, its role in tumor
      cell proliferation or migration remains unclear. Therefore, this study aimed to
      suppress STAT6 and Anoctamin-1 protein expression in gastric cancer cells to test
      the inhibitory effects on gastric cancer cell migration or invasion. MATERIALS
      AND METHODS: MTT colorimetry was used to test cell proliferation. Western blot
      was used to measure STAT6 and Anoctamin-1 expression before and after small
      interfering RNA (siRNA) treatment. A scratch assay was performed to measure cell
      migration, followed by Transwell chamber assay analysis of cell invasion.
      RESULTS: After STAT6 siRNA interference, the expression of STAT6 and Anoctamin-1
      was significantly decreased in the gastric carcinoma cell line. Anoctamin-1 siRNA
      interference only decreased its protein expression, but not STAT6 protein
      expression. Interference of STAT6 or Anoctamin-1 reduced their protein expression
      and inhibited proliferation, migration, or invasion of gastric cancer cells.
      CONCLUSIONS: Inhibition of STAT6/Anoctamin-1 activation decreased proliferation,
      migration, or invasion of gastric cancer cells, suggesting that the
      STAT6/Anoctamin-1 pathway might be a novel target for treating gastric cancer.

PMID- 29466036
TI  - Pharmacokinetics of buprenorphine after intravenous and oral transmucosal
      administration in guinea pigs (Cavia porcellus).
AB  - OBJECTIVE To determine pharmacokinetics and sedative effects of buprenorphine
      after IV and oral transmucosal (OTM) administration in guinea pigs. ANIMALS 14
      male guinea pigs (6 adults for preliminary experiment; eight 8 to 11-week-old
      animals for primary study). PROCEDURES A preliminary experiment was conducted to
      determine an appropriate buprenorphine dose. In the primary study, buprenorphine
      (0.2 mg/kg) was administered IV or OTM, and blood samples were obtained. The pH
      of the oral cavity was measured before OTM administration. Sedation was scored
      for 6 hours on a scale of 0 to 3 (0 = no sedation and 3 = heavy sedation). After
      a 7-day washout period, procedures were repeated in a crossover manner. Plasma
      buprenorphine concentration was quantified, and data were analyzed with a
      noncompartmental pharmacokinetic approach. RESULTS Mean peak plasma buprenorphine
      concentrations were 46.7 and 2.4 ng/mL after IV and OTM administration,
      respectively. Mean time to maximum plasma buprenorphine concentration was 1.5 and
      71.2 minutes, and mean terminal half-life was 184.9 and 173.0 minutes for IV and
      OTM administration, respectively. There was a range of sedation effects (0 to 2)
      for both routes of administration, which resolved within the 6-hour time frame.
      CONCLUSIONS AND CLINICAL RELEVANCE On the basis of pharmacokinetic parameters for
      this study, buprenorphine at 0.2 mg/kg may be administered IV every 7 hours or
      OTM every 4 hours to maintain a target plasma concentration of 1 ng/mL. Further
      studies are needed to evaluate administration of multiple doses and sedative
      effects in guinea pigs with signs of pain.

PMID- 29466037
TI  - Time required to achieve maximum concentration of amikacin in synovial fluid of
      the distal interphalangeal joint after intravenous regional limb perfusion in
      horses.
AB  - OBJECTIVE To determine the maximum concentration (Cmax) of amikacin and time to
      Cmax (Tmax) in the distal interphalangeal (DIP) joint in horses after IV regional
      limb perfusion (IVRLP) by use of the cephalic vein. ANIMALS 9 adult horses.
      PROCEDURES Horses were sedated and restrained in a standing position and then
      subjected to IVRLP (2 g of amikacin sulfate diluted to 60 mL with saline [0.9%
      NaCl] solution) by use of the cephalic vein. A pneumatic tourniquet was placed 10
      cm proximal to the accessory carpal bone. Perfusate was instilled with a
      peristaltic pump over a 3-minute period. Synovial fluid was collected from the
      DIP joint 5, 10, 15, 20, 25, and 30 minutes after IVRLP; the tourniquet was
      removed after the 20-minute sample was collected. Blood samples were collected
      from the jugular vein 5, 10, 15, 19, 21, 25, and 30 minutes after IVRLP. Amikacin
      was quantified with a fluorescence polarization immunoassay. Median Cmax of
      amikacin and Tmax in the DIP joint were determined. RESULTS 2 horses were
      excluded because an insufficient volume of synovial fluid was collected. Median
      Cmax for the DIP joint was 600 MUg/mL (range, 37 to 2,420 MUg/mL). Median Tmax
      for the DIP joint was 15 minutes. CONCLUSIONS AND CLINICAL RELEVANCE Tmax of
      amikacin was 15 minutes after IVRLP in horses and Cmax did not increase > 15
      minutes after IVRLP despite maintenance of the tourniquet. Application of a
      tourniquet for 15 minutes should be sufficient for completion of IVRLP when
      attempting to achieve an adequate concentration of amikacin in the synovial fluid
      of the DIP joint.

PMID- 29466040
TI  - Determination of anatomic landmarks for optimal placement in captive-bolt
      euthanasia of goats.
AB  - OBJECTIVE To determine the optimal anatomic site and directional aim of a
      penetrating captive bolt (PCB) for euthanasia of goats. SAMPLE 8 skulls from
      horned and polled goat cadavers and 10 anesthetized horned and polled goats
      scheduled to be euthanized at the end of a teaching laboratory. PROCEDURES
      Sagittal sections of cadaver skulls from 8 horned and polled goats were used to
      determine the ideal anatomic site and aiming of a PCB to maximize damage to the
      midbrain region of the brainstem for euthanasia. Anatomic sites for ideal
      placement and directional aiming were confirmed by use of 10 anesthetized horned
      and polled goats. RESULTS Clinical observation and postmortem examination of the
      sagittal sections of skulls from the 10 anesthetized goats that were euthanized
      confirmed that perpendicular placement and firing of a PCB at the intersection of
      2 lines, each drawn from the lateral canthus of 1 eye to the middle of the base
      of the opposite ear, resulted in consistent disruption of the midbrain and
      thalamus in all goats. Immediate cessation of breathing, followed by a loss of
      heartbeat in all 10 of the anesthetized goats, confirmed that use of this site
      consistently resulted in effective euthanasia. CONCLUSIONS AND CLINICAL RELEVANCE
      Damage to the brainstem and key adjacent structures may be accomplished by firing
      a PCB perpendicular to the skull over the anatomic site identified at the
      intersection of 2 lines, each drawn from the lateral canthus of 1 eye to the
      middle of the base of the opposite ear.

PMID- 29466041
TI  - Histologic investigation of airway inflammation in postmortem lung samples from
      racehorses.
AB  - OBJECTIVE To describe histologic findings in the small airways during postmortem
      examination of actively racing horses and to quantify the degree of airway
      inflammation by use of a semiquantitative scoring system. SAMPLE Lung tissues
      obtained from 95 horses (Thoroughbreds, Standardbreds, and Quarter Horses) that
      had been actively racing or training. PROCEDURES 10 standardized lung sections
      were obtained during postmortem examination of 37 horses that had been actively
      racing or training, and 2 histologic sections of the caudodorsal lung lobes
      previously collected from each of 58 horses that died or were euthanized during
      racing or training were also obtained. Sections were evaluated by use of a
      validated histologic small airway scoring system. RESULTS Scores for inflammatory
      cells, smooth muscle, and hemosiderin typically were high. Signalment and cause
      of death were not significant predictors of lung scores. Lung sample location was
      a significant predictor, with the highest scores in the caudal and dorsal
      sections. Inflammatory cell infiltration in peribronchiolar tissues, smooth
      muscle hyperplasia, and hemosiderin (prevalence of 86%, 98%, and 80%,
      respectively) were common findings in lungs of these horses, with the caudodorsal
      regions more severely affected. Correlation was moderate between smooth muscle
      hyperplasia and inflammatory cell infltration, with minimal correlation between
      hemosiderin and inflammatory cell infiltration. CONCLUSIONS AND CLINICAL
      RELEVANCE Inflammatory airway disease has been identified by use of
      bronchoalveolar lavage in young athletic horses throughout the world. In the
      study reported here, pathological changes were detected in the wall of small
      airways of horses that were actively training or racing.

PMID- 29466042
TI  - Use of a 3-Telsa magnet to perform delayed gadolinium-enhanced magnetic resonance
      imaging of the distal interphalangeal joint of horses with and without naturally
      occurring osteoarthritis.
AB  - OBJECTIVE To characterize delayed gadolinium-enhanced MRI of cartilage (dGEMRIC)
      features of healthy hyaline cartilage of the distal interphalangeal joint (DIPJ)
      of horses, to determine whether dGEMRIC can be used to differentiate various
      stages of naturally occurring osteoarthritis of the DIPJ, and to correlate
      relaxation times determined by dGEMRIC with the glycosaminoglycan concentration,
      water content, and macroscopic and histologic findings of hyaline cartilage of
      DIPJs with and without osteoarthritis. SAMPLE 1 cadaveric forelimb DIPJ from each
      of 12 adult warmblood horses. PROCEDURES T1-weighted cartilage relaxation times
      were obtained for predetermined sites of the DIPJ before (T1preGd) and after
      (T1postGd) intra-articular gadolinium administration. Corresponding cartilage
      sites underwent macroscopic, histologic, and immunohistochemical evaluation, and
      cartilage glycosaminoglycan concentration and water content were determined.
      Median T1preGd and T1postGd were correlated with macroscopic, histologic, and
      biochemical data. Mixed generalized linear models were created to evaluate the
      effects of cartilage site, articular surface, and macroscopic and histologic
      scores on relaxation times. RESULTS 122 cartilage specimens were analyzed. Median
      T1postGd was lower than the median T1preGd for normal and diseased cartilage.
      Both T1preGd and T1postGd were correlated with macroscopic and histologic scores,
      whereby T1preGd increased and T1postGd decreased as osteoarthritis progressed.
      There was topographic variation of T1preGd and T1postGd within the DIPJ.
      Cartilage glycosaminoglycan concentration and water content were significantly
      correlated with T1preGd and macroscopic and histologic scores but were not
      correlated with T1postGd. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated
      that dGEMRIC relaxation times varied for DIPJs with various degrees of
      osteoarthritis. These findings may help facilitate early detection of
      osteoarthritis.

PMID- 29466043
TI  - Neuropathologic features of the hippocampus and amygdala in cats with familial
      spontaneous epilepsy.
AB  - OBJECTIVE To investigate epilepsy-related neuropathologic changes in cats of a
      familial spontaneous epileptic strain (ie, familial spontaneous epileptic cats
      [FSECs]). ANIMALS 6 FSECs, 9 age-matched unrelated healthy control cats, and 2
      nonaffected (without clinical seizures)dams and 1 nonaffected sire of FSECs.
      PROCEDURES Immunohistochemical analyses were used to evaluate hippocampal
      sclerosis, amygdaloid sclerosis, mossy fiber sprouting, and granule cell
      pathological changes. Values were compared between FSECs and control cats.
      RESULTS Significantly fewer neurons without gliosis were detected in the third
      subregion of the cornu ammonis (CA) of the dorsal and ventral aspects of the
      hippocampus as well as the central nucleus of the amygdala in FSECs versus
      control cats. Gliosis without neuronal loss was also observed in the CA4
      subregion of the ventral aspect of the hippocampus. No changes in mossy fiber
      sprouting and granule cell pathological changes were detected. Moreover, similar
      changes were observed in the dams and sire without clinical seizures, although to
      a lesser extent. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that the
      lower numbers of neurons in the CA3 subregion of the hippocampus and the central
      nucleus of the amygdala were endophenotypes of familial spontaneous epilepsy in
      cats. In contrast to results of other veterinary medicine reports, severe
      epilepsy-related neuropathologic changes (eg, hippocampal sclerosis, amygdaloid
      sclerosis, mossy fiber sprouting, and granule cell pathological changes) were not
      detected in FSECs. Despite the use of a small number of cats with infrequent
      seizures, these findings contributed new insights on the pathophysiologic
      mechanisms of genetic-related epilepsy in cats.

PMID- 29466044
TI  - Use of high-field and low-field magnetic resonance imaging to describe the
      anatomy of the proximal portion of the tarsal region of nonlame horses.
AB  - OBJECTIVE To use high-field and low-field MRI to describe the anatomy of the
      proximal portion of the tarsal region (proximal tarsal region) of nonlame horses.
      SAMPLE 25 cadaveric equine tarsi. PROCEDURES The proximal portion of 1 tarsus
      from each of 25 nonlame horses with no history of tarsal lameness underwent high
      field (1.5-T) and low-field (0.27-T) MRI. Resulting images were used to
      subjectively describe the anatomy of that region and obtain measurements of the
      collateral ligaments of the tarsocrural joint. RESULTS Long and short components
      of the lateral and medial collateral ligaments of the tarsocrural joint were
      identified. Various bundles of the short collateral ligaments were difficult to
      delineate on low-field images. Ligaments typically had low signal intensity in
      all sequences; however, multiple areas of increased signal intensity were
      identified at specific locations in most tarsi. This signal intensity was
      attributed to focal magic angle effect associated with orientation of collagen
      fibers within the ligaments at those locations. Subchondral bone of the distal
      aspect of the tibia was uniform in thickness, whereas that of the medial
      trochlear ridge of the talus was generally thicker than that of the lateral
      trochlear ridge. In most tarsi, subchondral bone of the talocalcaneal joint
      decreased in thickness from proximal to distal. CONCLUSIONS AND CLINICAL
      RELEVANCE Results generated in this study can be used as a reference for
      interpretation of MRI images of the proximal tarsal region in horses.

PMID- 29466045
TI  - Correction: Effects of stacked wedge pads and chains applied to the forefeet of
      Tennessee Walking Horses for a five-day period on behavioral and biochemical
      indicators of pain, stress, and inflammation.

PMID- 29466046
TI  - Impact of synthetic canine cerumen on in vitro penetration of auricular skin of
      dogs by florfenicol, terbinafine, and betamethasone acetate.
AB  - OBJECTIVE To determine the pharmacokinetics of florfenicol, terbinafine, and
      betamethasone acetate after topical application to canine auricular skin and the
      influence of synthetic canine cerumen on pharmacokinetics. SAMPLE Auricular skin
      from 6 euthanized shelter dogs (3 females and 3 neutered males with no visible
      signs of otitis externa). PROCEDURES Skin adjacent to the external opening of the
      ear canal was collected and prepared for use in a 2-compartment flow-through
      diffusion cell system to evaluate penetration of an otic gel containing
      florfenicol, terbinafine, and betamethasone acetate over a 24-hour period.
      Radiolabeled 14C-terbinafine hydrochloride and 3H-betamethasone acetate were
      added to the gel to determine dermal penetration and distribution. Florfenicol
      absorption was determined by use of high-performance liquid chromatography-UV
      detection. Additionally, the effect of synthetic canine cerumen on the
      pharmacokinetics of all compounds was evaluated. RESULTS During the 24-hour
      experiment, mean +/- SD percentage absorption without the presence of synthetic
      canine cerumen was 0.28 +/- 0.09% for 3H-betamethasone acetate, 0.06 +/- 0.06%
      for florfenicol, and 0.06 +/- 0.02% for 14C-terbinafine hydrochloride. Absorption
      profiles revealed no impact of synthetic canine cerumen on skin absorption for
      all 3 active compounds in the gel or on skin distribution of 3H-betamethasone
      acetate and 14C-terbinafine hydrochloride. CONCLUSIONS AND CLINICAL RELEVANCE 3H
      betamethasone acetate, 14C-terbinafine hydrochloride, and florfenicol were all
      absorbed in vitro through healthy auricular skin specimens within the first 24
      hours after topical application. Synthetic canine cerumen had no impact on dermal
      absorption in vitro, but it may serve as a temporary reservoir that prolongs the
      release of topical drugs.

PMID- 29466047
TI  - Optimized computed tomography protocol for assessment of dentition in alpacas.
AB  - OBJECTIVE To determine the optimal protocol for acquisition of CT images of the
      dentition in alpacas. ANIMALS 3 healthy adult male alpacas. PROCEDURES Each
      alpaca was anesthetized with an IM injection of a combination of ketamine,
      xylazine, and butorphanol and positioned in sternal recumbency on the CT couch
      with its legs folded in a natural cush position and its head positioned within
      the isocenter of the gantry of a 64-slice CT scanner. Images were acquired by
      means of 6 protocols (sequential and helical modes at slice thicknesses of 1.25,
      2.5, and 5 mm). Five images (2 molar, 2 premolar, and mandibular incisor teeth)
      were selected from each protocol for evaluation by 3 veterinary radiologists. For
      each image, tooth root visibility and sharpness and image noise artifact were
      subjectively evaluated on a 3-point scoring system. RESULTS Slice thickness
      significantly affected tooth root visibility and tooth root sharpness but did not
      affect image noise artifact. Acquisition mode significantly affected tooth root
      visibility and tooth root sharpness as well as image noise artifact. Tooth root
      visibility and sharpness did not differ significantly between the helical and
      sequential images when the slice thickness was 1.25 mm. Image noise artifact was
      greater for helical images than sequential images but did not differ by slice
      thickness within either acquisition mode. CONCLUSIONS AND CLINICAL RELEVANCE
      Results indicated that for a 64-slice CT scanner, the optimal protocol for the
      acquisition of CT images of the dentition in alpacas was a sequential scan with a
      slice thickness of 1.25 mm.

PMID- 29466048
TI  - Effects of dexmedetomidine combined with commonly administered opioids on
      clinical variables in dogs.
AB  - OBJECTIVE To evaluate cardiopulmonary, sedative, and antinociceptive effects of
      dexmedetomidine combined with commonly administered opioids in dogs. ANIMALS 8
      healthy Beagles. PROCEDURES Dogs were sedated by IM administration of each of 7
      treatments. Treatments comprised dexmedetomidine (0.01 mg/kg; Dex) and the same
      dose of dexmedetomidine plus butorphanol (0.15 mg/kg; Dex-But), meperidine (5
      mg/kg; Dex-Mep), methadone (0.5 mg/kg; Dex-Meth), morphine (0.5 mg/kg; Dex-Mor),
      nalbuphine (0.5 mg/kg; Dex-Nal), or tramadol (5 mg/kg; Dex-Tram).
      Cardiorespiratory and arterial blood gas variables and sedative and
      antinociceptive scores were measured before drug injection (time 0; baseline) and
      at 15-minute intervals for 120 minutes. RESULTS Heart rate was reduced at all
      time points after injection of Dex-But, Dex-Mep, Dex-Meth, and Dex-Mor
      treatments. There was a significant reduction of mean arterial blood pressure for
      Dex-But, Dex-Mep, and Dex-Mor treatments at all time points, compared with
      baseline. There was a significant decrease in respiratory rate, compared with the
      baseline value, for Dex, Dex-But, Dex-Meth, and Dex-Tram treatments from 15 to
      120 minutes. A significant decrease in arterial blood pH was detected from
      baseline to 120 minutes for all treatments, with differences among Dex, Dex-Mep,
      and Dex-Mor. Reduction in Pao2 was greater for the Dex-Mep treatment than for the
      other treatments. The highest sedation scores were detected for Dex-Mep and Dex
      Meth treatments. Antinociceptive effects were superior for Dex-But, Dex-Meth, Dex
      Mor, and Dex-Nal treatments. CONCLUSIONS AND CLINICAL RELEVANCE Drug combinations
      caused similar cardiorespiratory changes, with greater sedative effects for Dex
      Mep and Dex-Meth and superior antinociceptive effects for Dex-But, Dex-Meth, Dex
      Mor, and Dex-Nal.

PMID- 29466049
TI  - Use of pressure mapping for quantitative analysis of pressure points induced by
      external coaptation of the distal portion of the pelvic limb of dogs.
AB  - OBJECTIVE To quantitatively measure the amount of pressure induced at the
      calcaneus and cranial tibial surface of dogs by use of 2 cast configurations.
      ANIMALS 13 client- or student-owned dogs. PROCEDURES Pressure sensors were placed
      over the calcaneus and cranial tibial surface. Dogs then were fitted with a
      fiberglass cast on a pelvic limb extending from the digits to the stifle joint
      (tall cast). Pressure induced over the calcaneus and proximal edge of the cast at
      the level of the cranial tibial surface was simultaneously recorded during
      ambulation. Subsequently, the cast was shortened to end immediately proximal to
      the calcaneus (short cast), and data acquisition was repeated. Pressure at the
      level of the calcaneus and cranial tibial surface for both cast configurations
      was compared by use of paired t tests. RESULTS The short cast created
      significantly greater peak pressure at the level of the calcaneus (mean +/- SD,
      0.2 +/- 0.07 MPa), compared with peak pressure created by the tall cast (0.1 +/-
      0.06 MPa). Mean pressure at the proximal cranial edge of the cast was
      significantly greater for the short cast (0.2 +/- 0.06 MPa) than for the tall
      cast (0.04 +/- 0.03 MPa). CONCLUSIONS AND CLINICAL RELEVANCE A cast extended to
      the level of the proximal portion of the tibia caused less pressure at the level
      of the calcaneus and the proximal cranial edge of the cast. Reducing the amount
      of pressure at these locations may minimize the potential for pressure sores and
      other soft tissue injuries.

PMID- 29466050
TI  - Letters to the Editor.

PMID- 29466051
TI  - Effect of a syringe aspiration technique versus a mechanical suction technique
      and use of N-butylscopolammonium bromide on the quantity and quality of
      bronchoalveolar lavage fluid samples obtained from horses with the summer pasture
      endophenotype of equine asthma.
AB  - OBJECTIVE To evaluate the effect of 2 bronchoalveolar lavage (BAL) sampling
      techniques and the use of N-butylscopolammonium bromide (NBB) on the quantity and
      quality of BAL fluid (BALF) samples obtained from horses with the summer pasture
      endophenotype of equine asthma. ANIMALS 8 horses with the summer pasture
      endophenotype of equine asthma. PROCEDURES BAL was performed bilaterally (right
      and left lung sites) with a flexible videoendoscope passed through the left or
      right nasal passage. During lavage of the first lung site, a BALF sample was
      collected by means of either gentle syringe aspiration or mechanical suction with
      a pressure-regulated wall-mounted suction pump. The endoscope was then maneuvered
      into the contralateral lung site, and lavage was performed with the alternate
      fluid retrieval technique. For each horse, BAL was performed bilaterally once
      with and once without premedication with NBB (21-day interval). The BALF samples
      retrieved were evaluated for volume, total cell count, differential cell count,
      RBC count, and total protein concentration. RESULTS Use of syringe aspiration
      significantly increased total BALF volume (mean volume increase, 40 mL [approx
      7.5% yield]) and decreased total RBC count (mean decrease, 142 cells/MUL),
      compared with use of mechanical suction. The BALF nucleated cell count and
      differential cell count did not differ between BAL procedures. Use of NBB had no
      effect on BALF retrieval. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated
      that retrieval of BALF by syringe aspiration may increase yield and reduce
      barotrauma in horses at increased risk of bronchoconstriction and bronchiolar
      collapse. Further studies to determine the usefulness of NBB and other
      bronchodilators during BAL procedures in horses are warranted.

PMID- 29466052
TI  - Long noncoding RNA SNHG1 promotes non-small cell lung cancer progression by up
      regulating MTDH via sponging miR-145-5p.
AB  - Long noncoding RNAs participate in the progression and initiation of non-small
      cell lung cancer (NSCLC), although the mechanism remains unknown. The lncRNA
      identified as small nucleolar RNA host gene 1 ( SNHG1) is a novel lncRNA that is
      increased in multiple human cancers; however, the regulatory mechanism requires
      further investigation. In this study, we discovered that SNHG1 was markedly up
      regulated in NSCLC tissues and cells and that SNHG1 silencing decreased tumor
      volumes. Moreover, we explored its regulatory mechanism and found that SNHG1
      directly bound to microRNA (miRNA)-145-5p, isolating miR-145-5p from its target
      gene MTDH. Inhibition of SNHG1 suppressed NSCLC cell viability, proliferation,
      migration, and invasion in vitro, but its effect was rescued by miR-145-5p
      inhibition. These results demonstrate that SNHG1 contributes to NSCLC progression
      by modulating the miR-145-5p/ MTDH axis, and it could potentially be a
      therapeutic target as well as a diagnostic marker.-Lu, Q., Shan, S., Li, Y., Zhu,
      D., Jin, W., Ren, T. Long noncoding RNA SNHG1 promotes non-small cell lung cancer
      progression by up-regulating MTDH via sponging miR-145-5p.

PMID- 29466053
TI  - Interplay between gut microbiota and p66Shc affects obesity-associated insulin
      resistance.
AB  - The 66 kDa isoform of the mammalian Shc gene promotes adipogenesis, and p66Shc-/-
      mice accumulate less body weight than wild-type (WT) mice. As the metabolic
      consequences of the leaner phenotype of p66Shc-/- mice is debated, we
      hypothesized that gut microbiota may be involved. We confirmed that p66Shc-/-
      mice gained less weight than WT mice when on a high-fat diet (HFD), but they were
      not protected from insulin resistance and glucose intolerance. p66Shc deletion
      significantly modified the composition of gut microbiota and their modification
      after an HFD. This was associated with changes in gene expression of Il-1b and
      regenerating islet-derived protein 3 gamma ( Reg3g) in the gut and in systemic
      trimethylamine N-oxide and branched chain amino acid levels, despite there being
      no difference in intestinal structure and permeability. Depleting gut microbiota
      at the end of HFD rendered both strains more glucose tolerant but improved
      insulin sensitivity only in p66Shc-/- mice. Microbiota-depleted WT mice cohoused
      with microbiota-competent p66Shc-/- mice became significantly more insulin
      resistant than WT mice cohoused with WT mice, despite no difference in weight
      gain. These findings reconcile previous inconsistent observations on the
      metabolic phenotype of p66Shc-/- mice and illustrate the complex microbiome-host
      genotype interplay under metabolic stress.-Ciciliot, S., Albiero, M., Campanaro,
      S., Poncina, N., Tedesco, S., Scattolini, V., Dalla Costa, F., Cignarella, A.,
      Vettore, M., Di Gangi, I. M., Bogialli, S., Avogaro, A., Fadini, G. P. Interplay
      between gut microbiota and p66Shc affects obesity-associated insulin resistance.

PMID- 29466055
TI  - Nature Versus Nurture: Have Performance Gaps Between Men and Women Reached an
      Asymptote?
AB  - Men outperform women in sports requiring muscular strength and/or endurance, but
      the relative influence of "nurture" versus "nature" remains difficult to
      quantify. Performance gaps between elite men and women are well documented using
      world records in second, centimeter, or kilogram sports. However, this approach
      is biased by global disparity in reward structures and opportunities for women.
      Despite policies enhancing female participation (Title IX legislation), US women
      only closed performance gaps by 2% and 5% in Olympic Trial swimming and running,
      respectively, from 1972 to 1980 (with no change thereafter through 2016).
      Performance gaps of 13% in elite middistance running and 8% in swimming (~4-min
      duration) remain, the 5% differential between sports indicative of load carriage
      disadvantages of higher female body fatness in running. Conversely, sprint
      swimming exhibits a greater sex difference than sprint running, suggesting
      anthropometric/power advantages unique to swim-block starts. The ~40-y plateau in
      the performance gap suggests a persistent dominance of biological influences (eg,
      longer limb levers, greater muscle mass, greater aerobic capacity, and lower fat
      mass) on performance. Current evidence suggests that women will not swim or run
      as fast as men in Olympic events, which speaks against eliminating sex
      segregation in these individual sports. Whether hormone reassignment sufficiently
      levels the playing field in Olympic sports for transgender females (born and
      socialized male) remains an issue to be tackled by sport-governing bodies.

PMID- 29466054
TI  - The role of Rpgrip1l, a component of the primary cilium, in adipocyte development
      and function.
AB  - Genetic variants within the FTO (alpha-ketoglutarate-dependent dioxygenase) gene
      have been strongly associated with a modest increase in adiposity as a result of
      increased food intake. These risk alleles are associated with decreased
      expression of both FTO and neighboring RPGRIP1L (retinitis pigmentosa GTPase
      regulator-interacting protein 1 like). RPGRIP1L encodes a protein that is
      critical to the function of the primary cilium, which conveys extracellular
      information to the cell. Rpgrip1l+/- mice exhibit increased adiposity, in part,
      as a result of hyperphagia. Here, we describe the effects of Rpgrip1l in
      adipocytes that may contribute to the adiposity phenotype observed in these
      animals and possibly in humans who segregate for FTO risk alleles. Loss of
      Rpgrip1l in 3T3-L1 preadipocytes increased the number of cells that are capable
      of differentiating into mature adipocytes. Knockout of Rpgrip1l in mature
      adipocytes using Adipoq-Cre did not increase adiposity in mice that were fed chow
      or a high-fat diet. We also did not observe any effects of Rpgrip1l knockdown in
      mature 3T3-L1 adipocytes. Thus, to the extent that Rpgrip1l affects cell
      autonomous adipose tissue function, it may do so as a result of the effects
      conveyed in preadipocytes in which the primary cilium is functionally important.
      We propose that decreased RPGRIP1L expression in preadipocytes in humans who
      segregate for FTO obesity risk alleles may increase the storage capacity of
      adipose tissue.-Martin Carli, J. F., LeDuc, C. A., Zhang, Y., Stratigopoulos, G.,
      Leibel, R. L. The role of Rpgrip1l, a component of the primary cilium, in
      adipocyte development and function.

PMID- 29466056
TI  - A GUIDE TO FOLLOW-ON BIOLOGICS AND BIOSIMILARS WITH A FOCUS ON INSULIN.
AB  - OBJECTIVE: Many healthcare providers in the U.S. are not familiar with follow-on
      biologics and biosimilars nor with their critical distinctions from standard
      generics. Our aim is to provide a detailed review of both, with a focus on
      insulins in the U.S. regulatory system. METHODS: Literature has been reviewed to
      provide information on various aspects of biosimilars and a follow-on biologic of
      insulin. This will include structure, efficacy, cost, switching, and legal
      issues. RESULTS: Biologic products are large, complex molecules derived from
      living sources. Follow-on biologics are copies of the original innovator
      biologics. It is not possible to copy their structure exactly, leading to
      possible differences in efficacy and safety. Thus, regulations involving
      biologics are complex. Follow-on biologics are regulated under two Federal laws
      until March 23, 2020: the Public Health Service Act (PHS Act) and the Federal
      Food, Drug, and Cosmetic Act. Biosimilars are follow-on biologics which have been
      approved via the PHS Act. They consist of those which are "highly similar" to the
      reference drug and those which are "expected" to produce the same clinical result
      as the reference drug (interchangeable biosimilars). Interchangeable biosimilars
      have been determined by the U.S. Food and Drug Administration to be substitutable
      by the pharmacist "without the intervention" of the prescriber. From the patient
      perspective, switching to a follow-on biologic may necessitate a change in
      delivery device, which may create issues for patient adherence and dosing.
      CONCLUSION: Although they present several challenges in terms of regulation and
      acceptance, follow-on biologics have the potential to significantly reduce costs
      for patients requiring insulin therapy. ABBREVIATIONS: BLA = biologics license
      application EU = European Union FDA = Food and Drug Administration FD&C = Food,
      Drug, and Cosmetic HCPCS = Healthcare Common Procedure Coding System INN =
      internatinal nonproprietary name NDA = new drug application PHS = Public Health
      Service.

PMID- 29466057
TI  - ZOLEDRONIC ACID VERSUS ALENDRONATE IN THE TREATMENT OF CHILDREN WITH OSTEOGENESIS
      IMPERFECTA: A 2-YEAR CLINICAL STUDY.
AB  - OBJECTIVE: Bisphosphonates have been demonstrated to increase the bone mineral
      density (BMD) of osteogenesis imperfecta (OI) patients. We aimed to compare the
      efficacy and safety of intravenous zoledronic acid and oral alendronate in
      patients with OI. METHODS: A total of 161 patients with OI ranging from 2 to 16
      years old were included and randomized at a 2:1 ratio to receive either weekly
      oral alendronate (ALN) 70 mg or a once-yearly infusion of zoledronic acid (ZOL)
      for 2 years. The primary endpoints were percentage change from baseline in lumbar
      spine (LS) BMD and change in Z-scores of LS BMD. RESULTS: A total of 136 patients
      with OI completed the 2-year clinical study, 90 of whom were assigned to receive
      ALN, while 46 received ZOL treatment. The percentage change in LS BMD was 60.01
      +/- 7.08% in the ALN group and 62.04 +/- 5.9% in the ZOL group ( P = .721). The
      corresponding BMD Z-score increased by 0.50 +/- 0.05 in the ALN group and 0.71 +/
      0.06 in the ZOL group ( P = .013). ZOL was superior to ALN in reducing the
      clinical fracture rate (hazard ratio, 0.23; 95% confidence interval, 0.118 to
      0.431). There was no difference in the incidence of severe side effects between
      the two groups. CONCLUSION: A once-yearly 5 mg infusion of ZOL and weekly oral
      ALN had similar effects in increasing BMD and reducing bone resorption in
      children and adolescents with OI. ZOL was superior to ALN in reducing the
      clinical fracture rate. ABBREVIATIONS: 25OHD = 25-hydroxyvitamin D ALN =
      alendronate ALP = alkaline phosphatase beta-CTX = cross-linked C-telopeptide of
      type I collagen BMD = bone mineral density BP = bisphosphonate FN = femoral neck
      LS = lumbar spine OI = osteogenesis imperfecta SAE = severe adverse event ZOL =
      zoledronic acid.

PMID- 29466058
TI  - CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND
      AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE QUALITY OF DXA SCANS AND REPORTS.
AB  - OBJECTIVE: High-quality dual-energy X-ray absorptiometry (DXA) scans are
      necessary for accurate diagnosis of osteoporosis and monitoring of therapy;
      however, DXA scan reports may contain errors that cause confusion about diagnosis
      and treatment. This American Association of Clinical Endocrinologists/American
      College of Endocrinology consensus statement was generated to draw attention to
      many common technical problems affecting DXA report conclusions and provide
      guidance on how to address them to ensure that patients receive appropriate
      osteoporosis care. METHODS: The DXA Writing Committee developed a consensus based
      on discussion and evaluation of available literature related to osteoporosis and
      osteodensitometry. RESULTS: Technical errors may include errors in scan
      acquisition and/or analysis, leading to incorrect diagnosis and reporting of
      change over time. Although the International Society for Clinical Densitometry
      advocates training for technologists and medical interpreters to help eliminate
      these problems, many lack skill in this technology. Suspicion that reports are
      wrong arises when clinical history is not compatible with scan interpretation
      (e.g., dramatic increase/decrease in a short period of time; declines in
      previously stable bone density after years of treatment), when different scanners
      are used, or when inconsistent anatomic sites are used for monitoring the
      response to therapy. Understanding the concept of least significant change will
      minimize erroneous conclusions about changes in bone density. CONCLUSION:
      Clinicians must develop the skills to differentiate technical problems, which
      confound reports, from real biological changes. We recommend that clinicians
      review actual scan images and data, instead of relying solely on the impression
      of the report, to pinpoint errors and accurately interpret DXA scan images.
      ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists; BMC =
      bone mineral content; BMD = bone mineral density; DXA = dual-energy X-ray
      absorptiometry; ISCD = International Society for Clinical Densitometry; LSC =
      least significant change; TBS = trabecular bone score; WHO = World Health
      Organization.

PMID- 29466059
TI  - INITIATION OF PATIENTS ONTO LONG-ACTING SOMATOSTATIN ANALOGUE THERAPY FOR
      NEUROENDOCRINE TUMORS: A SINGLE-CENTER REVIEW OF PRACTICE.
AB  - OBJECTIVE: Neuroendocrine tumors (NETs) are being seen increasingly frequently,
      and recent data show that long-acting somatostatin analogues have become a major
      initial treatment, regardless of whether the tumors are functioning or not.
      However, test dosing with subcutaneous (sc) octreotide is usually advised to
      assess longer-term tolerability, although this advice is mainly based on results
      with functioning tumors. The aim of the study was to assess the value of an
      initiating test dose of sc octreotide on the prediction of subsequent adverse
      events after treatment with the long-acting analogue. METHODS: In a single, large
      Centre of Excellence for NETs, a first cohort of patients (n = 24) was admitted
      overnight after an sc injection of octreotide, and then administered the
      analogue; a subsequent group (n = 53) had the test dose performed on an
      outpatient basis. Side effects were recorded after the test dose and subsequent
      treatment with the long-acting analogue. RESULTS: The test dose injection was of
      little value in predicting adverse events following the long-acting somatostatin
      analogue. CONCLUSION: Unless there are serious symptoms associated with a
      functioning NET, it is unnecessary to carry out a test dose; a change to this
      procedure will improve resource allocation and should enhance early initiation
      onto maintenance therapy. ABBREVIATIONS: CLARINET = Controlled study of
      lanreotide antiproliferative response in neuroendocrine tumors LAR = long-acting
      repeatable NET = neuroendocrine tumor PROMID = Placebo-controlled, double-blind,
      prospective, randomized study on the effect of octreotide LAR in the control of
      tumor growth in patients with meta-static neuroendocrine midgut tumors.

PMID- 29466060
TI  - LETTER TO THE EDITOR.

PMID- 29466061
TI  - LETTER TO THE EDITOR.

PMID- 29466062
TI  - MANAGEMENT OF DIABETES DURING AIR TRAVEL: A SYSTEMATIC LITERATURE REVIEW OF
      CURRENT RECOMMENDATIONS AND THEIR SUPPORTING EVIDENCE.
AB  - OBJECTIVE: Individuals with diabetes are increasingly seeking pretravel advice,
      but updated professional recommendations remain scant. We performed a systematic
      review on diabetes management during air travel to summarize current
      recommendations, assess supporting evidence, and identify areas of future
      research. METHODS: A systematic review of the English literature on diabetes
      management during air travel was undertaken utilizing PubMed and MEDLINE.
      Publications regarding general travel advice; adjustment of insulin and
      noninsulin therapies; and the use of insulin pumps, glucometers and subcutaneous
      glucose sensors at altitude were included. Gathered information was used to
      create an updated summary of glucose-lowering medication adjustment during air
      travel. RESULTS: Sixty-one publications were identified, most providing expert
      opinion and few offering primary data (47 expert opinion, 2 observational
      studies, 2 case reports, 10 device studies). General travel advice was uniform,
      with increasing attention to preflight security. Indications for oral
      antihyperglycemic therapy adjustments varied. There were few recommendations on
      contemporary agents and on nonhypoglycemic adverse events. There was little
      consensus on insulin adjustment protocols, many antedating current insulin
      formulations. Most publications advocated adjusting insulin pump time settings
      after arrival; however, there was disagreement on timing and rate adjustments.
      Glucometers and subcutaneous glucose sensors were reported to be less accurate at
      altitude, but not to an extent that would preclude their clinical use.
      CONCLUSION: Recommendations for diabetes management during air travel vary
      significantly and are mostly based on expert opinion. Data from systematic
      investigation on glucose-lowering medication adjustment protocols may support the
      development of a future consensus statement. ABBREVIATIONS: CSII = continuous
      subcutaneous insulin infusion (device) DPP-4 = dipeptidyl peptidase 4 EGA = error
      grid analysis GDH = glucose dehydrogenase GOX = glucose oxidase GLP1 = glucagon
      like peptide-1 NPH = neutral protamine Hagedorn SGLT2 = sodium-glucose
      cotransporter-2.

PMID- 29466063
TI  - Antiulcerative and Antinociceptive Activities of Casein and Whey Proteins.
AB  - The aim of this study was to evaluate the antiulcerative and antinociceptive
      activities of milk proteins using the induced gastric ulcer with ethanol rat
      model and the acetic acid-induced writhing mouse model. Casein (CN), (100, 300,
      and 1000 mg kg-1) doses presented antiulcerative activity on a dose-dependent
      manner with values of 30.8%, 41.4%, and 57.0% of inhibition measured using the
      ulcerative lesions index (ULI), respectively. Whey protein concentrate (WPC),
      (100, 300, and 1000 mg kg-1) doses presented antiulcerative activity on a dose
      dependent manner with values of 48.9%, 65.5%, and 68.22% of ULI inhibition,
      respectively. CN, casein hydrolysates (CNH), WPC, and whey protein hydrolysates
      (WPH), (3, 10, and 30 mg kg-1) doses presented antinociceptive activity using the
      acetic acid-induced writhing in the mouse model. CN (30 mg kg-1) presented a
      value of 40% of inhibition writhing, and CNH (30 mg kg-1) presented
      antinociceptive activity with a value up to 46% of writhing inhibition. WPC (30
      mg kg-1) presented a value of 52.50%, and WPH (30 mg kg-1) presented
      antinociceptive activity with a value up to 88.00% of writhing inhibition. In
      conclusion, CN and WPC demonstrated in vivo antiulcerative properties and
      represent a promising alternative to be used as protectors of the gastric mucosa.
      CNH and WPH demonstrated in vivo antiulcerative properties and represent a
      promising alternative to be used as natural analgesic.

PMID- 29466064
TI  - Exploring and Adapting a Conceptual Model of Sexual Positioning Practices and
      Sexual Risk Among HIV-Negative Black Men Who Have Sex With Men.
AB  - Estimates show a 50% lifetime human immunodeficiency virus (HIV) risk among Black
      men who have sex with men (BMSM) in the United States(U.S.). Studying the
      dynamics of sexual positioning practices among BMSM could provide insights into
      the disparities observed among U.S. groups of men who have sex with men (MSM).
      This study explored sexual positioning dynamics among HIV-negative BMSM and how
      they aligned with a theoretical model of sexual positioning and HIV/sexually
      transmitted infection (STI) risk among MSM. In-depth qualitative interviews were
      conducted with 29 HIV-negative BMSM between ages 25 and 35 in Los Angeles.
      Comments related to sexual behaviors were reviewed for relevance regarding oral
      or anal sexual positioning practices. Data presented represent the range of
      themes related to decision making regarding sexual positioning. Personal
      preference, partner attraction, HIV avoidance, and feeling obligated to practice
      partner preferences influenced sexual positioning. Drug use also affected
      decision making and was sometimes preferred in order to practice receptive anal
      intercourse. These variables build on the conceptual model of sexual positioning
      practices and sexual risk, and add understanding to the relationship between
      preferences, practices, and risk management. Future research on risk among HIV
      negative BMSM should quantify the relative impact of personal preferences,
      partner attraction, partner type, compromise, and substance use on sexual
      positioning practices and risk.

PMID- 29466065
TI  - Physical Preparation Factors That Influence Technical and Physical Match
      Performance in Professional Australian Football.
AB  - OBJECTIVES: To examine the collective influence of a range of physical
      preparation elements on selected performance measures during Australian football
      match play. DESIGN: Prospective and longitudinal. METHODS: Data were collected
      from 34 professional Australian football players from the same club during the
      2016 Australian Football League competition season. Match activity profiles and
      acute (7-d) and chronic (3-wk) training loads were collected using global
      positioning system devices. Training response was measured by well-being
      questionnaires completed prior to the main training session each week. Maximal
      aerobic running speed (MAS) was estimated by a 2-km time trial conducted during
      preseason. Coach ratings were collected from the senior coach and 4 assistants
      after each match on a 5-point Likert scale. Player ratings were obtained from a
      commercial statistics provider. Fifteen matches were analyzed. Linear mixed
      models were constructed to examine the collective influence of training-related
      factors on 4 performance measures. RESULTS: Muscle soreness had a small positive
      effect (ES: 0.12) on Champion Data rating points. Three-week average high-speed
      running distance had a small negative effect (ES: 0.14) on coach ratings. MAS had
      large to moderate positive effects (ES: 0.55 to 0.47) on relative total and high
      speed running distances. Acute total and chronic average total running distance
      had small positive (ES: 0.13) and negative (ES: 0.14) effects on relative total
      and high-speed running distance performed during matches, respectively.
      CONCLUSIONS: MAS should be developed to enhance players' running performance
      during competition. Monitoring of physical preparation data may assist in
      reducing injury and illness and increasing player availability but not enhance
      football performance.

PMID- 29466066
TI  - Effect of Graft Type on Balance and Hop Tests in Adolescent Males following
      Anterior Cruciate Ligament Reconstruction.
AB  - CONTEXT: Recent epidemiology studies indicated a steady increase of anterior
      cruciate ligament (ACL) injury in young athletes. ACL reconstruction (ACLR) is
      currently a standard of the care, but effect of ACLR graft including bone
      patellar tendon bone (BTB), hamstring tendon (HT), or iliotibial band (ITB) on
      balance and hop performance is understudied. OBJECTIVE: To compare balance and
      hop deficits between uninvolved and reconstructed limbs in each autograft type
      (aim 1) and among the three autograft groups (aim 2). SETTING: Biomechanical
      laboratory. PARTICIPANTS: Male ACLR patients who are younger than 22 years old
      (Total N=160; BTB N=19, HT N=108, ITB N=33). INTERVENTION: Approximately 6-9
      months following ACLR, Y-balance and 4 types of hop tests were measured
      bilaterally. MAIN OUTCOME MEASURES: Limb symmetry index of balance and hop tests
      within each graft type and between the 3 graft types. RESULTS: In the BTB group,
      significant anterior reach, single hop, triple hops, and cross-over hops deficits
      were observed on the ACLR limb compared to uninvolved limb. The HT group showed
      significant deficits in single hop, triple hops, and cross-over hops on the ACLR
      limb relative to the uninvolved limb. Compared to uninvolved limb, significantly
      decreased triple hops and 6 meter timed hop deficits in the ACLR limb were
      recorded in the ITB group. When controlling for confounders and comparing among
      the three autograft types, the only significant difference was anterior reach, in
      which the BTB group showed significant deficits. CONCLUSION: Compared to the
      uninvolved limb, significant hop deficits in ACLR limb were prevalent among
      adolescent ACLR patients at approximately 6-9 months postoperatively. After
      controlling covariates, significantly reduced anterior reach balance was found in
      BTB group as compared to the HT and ITB groups.

PMID- 29466067
TI  - A Narrative Analysis: Examining the Transition to Practice for the Full-Time
      Secondary School Athletic Trainer.
AB  - CONTEXT:   The transition to clinical practice is an important topic in athletic
      training because it is viewed as a stressful time that is accompanied by self
      doubt. Mentorship and previous experience support the transition to practice, but
      little information is available on the organizational entry of the athletic
      trainer (AT) who is employed full time in the secondary school setting.
      OBJECTIVE:   To understand the experiences of newly credentialed ATs in full-time
      positions in the secondary school setting. DESIGN:   Qualitative study. SETTING: 
      Secondary schools. PATIENTS OR OTHER PARTICIPANTS:   Seventeen ATs (4 men, 13
      women; age = 25 +/- 4 years) were employed full time in the secondary school
      setting. On average, the full-time ATs worked 40 +/- 10 hours per week. DATA
      COLLECTION AND ANALYSIS:   All participants completed a semistructured telephone
      interview with 1 researcher. Data were analyzed using a narrative analysis, and
      credibility was established by peer review and researcher triangulation. The
      narrative research paradigm guided our protocol and supported the rigor of the
      study. RESULTS:   Our analyses revealed that transition to practice was organic,
      such that the newly credentialed AT gained awareness by engaging in the role
      daily. Additionally, the transition process was facilitated by previous
      experience in the setting, mostly from educational training. Ongoing
      communication with various stakeholders (athletic directors, team physicians, and
      peer ATs) in the setting also assisted in the process of transitioning. Finally,
      mentorship from previous preceptors provided support during the transition
      process. CONCLUSIONS:   Transitioning into full-time clinical practice in the
      secondary school setting was informal and supported by professional relationships
      and past experiences. Past experiences allowed for awareness but also the
      development of mentoring relationships that continued beyond the clinical
      education experience. Communication also assisted the newly credentialed AT, as
      it provided feedback for legitimation by multiple stakeholders.

PMID- 29466068
TI  - Capture of Time-Loss Overuse Soccer Injuries in the National Collegiate Athletic
      Association's Injury Surveillance System, 2005-2006 Through 2007-2008.
AB  - CONTEXT:   Overuse injuries are reported to account for nearly 50% of sports
      injuries and, due to their progressive nature and the uncertainty regarding date
      of onset, are difficult to define and categorize. Comparing the capture rates of
      overuse injuries between injury-surveillance systems and medical records can
      clarify completeness and determinants of how overuse injuries are represented in
      injury-surveillance data. OBJECTIVE:   To estimate the capture rate of time-loss
      medical-attention overuse injuries in men's and women's soccer in the National
      Collegiate Athletic Association Injury Surveillance System (NCAA ISS) compared
      with medical records maintained by certified athletic trainers and assess the
      differences in completeness of capture and factors contributing to those
      differences. DESIGN:   Capture-recapture study. SETTING:   Fifteen NCAA
      institutions provided NCAA ISS and medical record data from men's and women's
      soccer programs from 2005-2006 through 2007-2008. PATIENTS OR OTHER PARTICIPANTS:
      National Collegiate Athletic Association men's and women's soccer players. MAIN
      OUTCOME MEASURE(S):   Time-loss medical-attention overuse injuries were defined
      as injuries with an overuse mechanism of injury in the NCAA ISS or medical
      records. Capture rates were calculated as the proportion of total overuse
      injuries classified as having overuse mechanisms in the NCAA ISS and the NCAA ISS
      and medical records combined. RESULTS:   The NCAA ISS captured 63.7% of the total
      estimated overuse mechanisms of injury in men's and women's soccer players. The
      estimated proportion of overuse injury mechanisms captured by both the NCAA ISS
      and medical records was 37.1%. The NCAA ISS captured more overuse injury
      mechanisms in men's soccer than in women's soccer (79.2% versus 45.0%, chi2 =
      9.60; P = .002) athletes. CONCLUSIONS:   From 2005-2006 through 2007-2008, the
      NCAA ISS captured only two thirds of time-loss medical-attention overuse
      mechanisms of injury in men's and women's soccer players. Future researchers
      should consider supplementing injury-surveillance data with a clinical record
      review to capture the burden of these injuries.

PMID- 29466069
TI  - Maintaining Professional Commitment as a Newly Credentialed Athletic Trainer in
      the Secondary School Setting.
AB  - CONTEXT:   Professional commitment, or one's affinity and loyalty to a career,
      has become a topic of interest in athletic training. The expanding research on
      the topic, however, has omitted newly credentialed athletic trainers (ATs). For
      an impressionable group of practitioners, transitioning to clinical practice can
      be stressful. OBJECTIVE:   To explore the professional commitment of newly
      credentialed ATs in the secondary school setting. SETTING:   Secondary school.
      DESIGN:   Qualitative study. PATIENTS OR OTHER PARTICIPANTS:   A total of 31
      newly credentialed ATs (6 men, 25 women; mean age = 24 +/- 3 years) participated.
      Of these, 17 ATs (4 men, 13 women; mean age = 25 +/- 4 years) were employed full
      time in the secondary school setting, and 14 ATs (2 men, 12 women; mean age =
      23.0 +/- 2.0 years) were graduate assistant students in the secondary school
      setting. DATA COLLECTION AND ANALYSIS:   All participants completed
      semistructured interviews, which focused on their experiences in the secondary
      school setting and transitioning into the role and setting. Transcripts were
      analyzed using the phenomenologic approach. Creditability was established by peer
      review, member checks, and researcher triangulation. RESULTS:   Four main
      findings related to the professional commitment of newly credentialed ATs in the
      secondary school setting were identified. Work-life balance, professional
      relationships formed with the student-athletes, enjoyment gained from working in
      the secondary school setting, and professional responsibility emerged as factors
      facilitating commitment. CONCLUSIONS:   Affective commitment is a primary
      facilitator of professional commitment. Newly credentialed ATs who enjoy their
      jobs and have time to engage in nonwork roles are able to maintain a positive
      professional commitment. Our findings align with the previous literature and help
      strengthen our understanding that rejuvenation and passion are important to
      professional commitment.

PMID- 29466071
TI  - Dynamics of the Metabolic Response During a Competitive 100-m Freestyle in Elite
      Male Swimmers.
AB  - PURPOSE: To compare the dynamics of maximal oxygen uptake ([Formula: see text]),
      blood lactate ([La]b), total energy expenditure (Etot), and contributions of the
      aerobic (Eaer), alactic anaerobic (Ean,al), and lactic anaerobic (Ean,lac)
      metabolic energy pathways over 4 consecutive 25-m laps (L0-25, L25-50, etc) of a
      100-m maximal freestyle swim. METHODS: Elite swimmers comprising 26 juniors (age
      = 16 [1] y) and 23 seniors (age = 24 [5] y) performed 100 m at maximal speed and
      then 3 trials (25, 50, and 75 m) at the same pace as that of the 100 m. [La]b was
      collected, and [Formula: see text] was measured 20 s postexercise. RESULTS: The
      estimated energetic contributions for the 100-m trial are presented as mean (SD):
      Eaer, 51% (8%); Ean,al, 18% (2%); Ean,lac, 31% (9%). [Formula: see text]
      increased from L0-25 to L25-50 (mean = 3.5 L.min-1; 90% confidence interval [CI],
      3.4-3.7 L.min-1 to mean = 4.2 L.min-1; 90% CI, 4.0-4.3 L.min-1) and then
      stabilized in the 2nd 50 m (mean = 4.1 L.min-1; 90% CI, 3.9-4.3 L.min-1 to mean =
      4.2 L.min-1; 90% CI, 4.0-4.4 L.min-1). Etot (juniors, 138 [18] kJ; seniors, 168
      [26] kJ), Ean,al (juniors, 27 [3] kJ; seniors, 30 [3] kJ), and Ean,lac (juniors,
      38 [12] kJ; seniors, 62 [24] kJ) were 11-58% higher in seniors. Faster swimmers
      (n = 26) had higher [Formula: see text], 90% CI 4.4-4.8 L.min-1 [Formula: see
      text] L.min-1, 90% CI 3.6-4.2 L.min-1), and Eaer power was associated with fast
      performances (P < .001). CONCLUSION: Faster swimmers were characterized by higher
      [Formula: see text] and less time to reach the highest [Formula: see text] at ~50
      m of the 100-m swim. Anaerobic qualities become more important with age.

PMID- 29466070
TI  - Orientation Process for Newly Credentialed Athletic Trainers in the Transition to
      Practice.
AB  - CONTEXT:   Orientation is an important part of socialization and transition to
      practice, yet the orientation process for newly credentialed athletic trainers
      (ATs) is unknown. OBJECTIVE:   To determine how newly credentialed ATs are
      oriented to their roles. DESIGN:   Cross-sectional study. SETTING:   Online
      survey. PATIENTS OR OTHER PARTICIPANTS:   Three hundred thirty-two of 1835 newly
      credentialed ATs (18%) certified and employed between January and September of
      2013 completed the survey (129 men, 203 women; age = 23.58 +/- 2.54 years). DATA
      COLLECTION AND ANALYSIS:   The survey consisted of demographic information (eg,
      employment setting, job title) and 2 sections: (1) orientation tactics and (2)
      usefulness of orientation tactics. For the first section, participants identified
      if various orientation tactics were included in their orientations (eg, policies
      and procedures review). For the second section, participants identified how
      useful each orientation tactic was on a Likert scale (1 = not useful, 4 = very
      useful). Descriptive statistics were calculated for each survey item. Mann
      Whitney U and Kruskal-Wallis tests were used to determine differences between
      demographic characteristics and orientation tactics. A Bonferroni correction
      accounted for multiple comparisons. A panel of experts established the content
      validity of the survey. The Cronbach alpha was used to establish internal
      consistency (alpha = 0.802) Results:  The most common orientation tactics were
      meeting with supervisors (n = 276, 82.9%) and staff members (eg, coaches; n =
      266, 79.9%) and learning responsibilities (n = 254, 76.2%). The least common
      orientation tactics were simulation of the emergency action plan (n = 66, 19.8%)
      and preceptor development (n = 71, 21.3%); however, preceptor development was not
      applicable to many participants. The most useful orientation tactics were
      simulating the emergency action plan (3.45/4.0) and meeting with staff members
      (3.44/4.0). Participants who felt their orientation prepared them for their roles
      were exposed to more tactics during orientation (Mann-Whitney U = 17 212, P <
      .001). CONCLUSIONS:   Many tactics were used to orient newly credentialed ATs to
      their roles, but orientations varied based on the practice setting.

PMID- 29466072
TI  - A Novel Auxiliary Device for Preventing Band Slippage After Laparoscopic
      Adjustable Gastric Banding: Infra-Band Fixation Using S-Loop.
AB  - BACKGROUND: Band slippage is known to be a troublesome complication of
      laparoscopic adjustable gastric banding (LAGB), often requiring surgical
      intervention. To prevent band slippage, a new auxiliary device "S-loop" was
      developed. METHODS: From July 2010 to January 2014, a total of 814 LAGBs were
      performed by a single surgeon. The patients were divided into two groups based on
      the application of S-loop: conventional LAGB group (n = 378) and S-loop group (n
      = 436). The operative outcomes were compared between the two groups. RESULTS: The
      mean operative time and the length of hospital stay were significantly longer in
      the conventional LAGB group than in the S-loop group (64.3 minutes versus 57.1
      minutes; P < .001 and 5.0 hours versus 3.6 hours; P < .001, respectively). The
      complications occurred in 7.1% of the conventional LAGB group and 1.6% in the S
      loop group (P < .001). Slippage was the most common complication: 13 cases were
      observed in the conventional LAGB group, whereas no slippage was observed in the
      S-loop group. CONCLUSION: Infra-band fixation using S-loop is a simple and
      effective method for preventing band slippage compared with the conventional
      LAGB.

PMID- 29466073
TI  - The Effects of Hip Mobilizations on Patient Outcomes: A Critically Appraised
      Topic.
AB  - Clinical Scenario: Hip osteoarthritis currently affects up to 28% percent of the
      population, and the number of affected Americans is expected to rise as the
      American population increases and ages.1,2 Limited hip range of motion (ROM) has
      been identified as a predisposing factor to hip osteoarthritis and limited
      patient function.3,4 Clinicians often apply therapy techniques, such as
      stretching and strengthening exercises, to improve hip ROM.5 Although traditional
      therapy has been recommended to improve hip ROM, the efficiency of the treatments
      within the literature are questionable due to lack of high quality studies.3-8
      More recently, clinicians have begun to utilize joint mobilization and the
      Mulligan Concept (MC) mobilization with movement (MWM) techniques to increase ROM
      at the hip;3-8 however, there is a paucity of research on the lasting effects of
      mobilizations. Given the difficulties in improving ROM immediately (within a
      single treatment), and with long-lasting results (over the course of months), 3-8
      it is imperative to examine the evidence for the effectiveness of traditional
      therapy techniques and more novel manual therapy techniques. Focused Clinical
      Question: Is there evidence to suggest manual mobilizations techniques at the hip
      are effective at treating hip ROM limitations?

PMID- 29466074
TI  - Prevalence and Survival Impact of Pretreatment Cancer-Associated Weight Loss: A
      Tool for Guiding Early Palliative Care.
AB  - PURPOSE: Cancer-associated weight loss is associated with poor prognosis in
      advanced malignancy; however, its pretreatment prevalence and survival impact are
      inadequately described in large cohorts. Such data, stratified by tumor type and
      stage, may facilitate the optimal and timely allocation of complementary care,
      leading to improvements in patient survival and quality of life. METHODS: We
      performed a retrospective cohort study of 3,180 consecutively treated adult
      patients with lung or GI (including colorectal, liver, and pancreatic) cancer.
      Pretreatment cancer-associated weight loss was based on the international
      consensus definition of cachexia. Prevalence and survival impact of pretreatment
      cancer-associated weight loss were evaluated using the Kaplan-Meier method and
      compared using log-rank test. RESULTS: Cancer-associated weight loss was observed
      at the time of cancer diagnosis in 34.1% of patients. Pretreatment weight loss
      was documented in 17.6%, 25.8%, 36.6%, and 43.3% of stage I, II, III, and IV
      cancers, respectively. Wasting was common regardless of tumor type, with
      prevalence at diagnosis ranging from 27.3% in patients with colorectal cancer to
      53.4% in patients with gastroesophageal cancer. Pretreatment weight loss was
      associated with reduced overall survival after adjusting for stage, size, grade,
      comorbidity, age, sex, and tobacco history (hazard ratio, 1.26; 95% CI, 1.13 to
      1.39). CONCLUSION: Pretreatment cancer-associated weight loss is common, even in
      early-stage disease, and is independently associated with reduced survival.
      Minimal weight loss represents a clinically distinct entity with an associated
      overall survival intermediate to that of no weight loss and overt wasting. Early
      diagnosis and treatment of cancer-associated wasting offers a novel therapeutic
      avenue for reducing cancer mortality.

PMID- 29466076
TI  - The Effects of Rigid Scapular Taping on the Subacromial Space in Athletes With
      and Without Rotator Cuff Tendinopathy: A Randomized-Controlled Study.
AB  - CONTEXT: Reduction of the subacromial space (SAS) during arm elevation may
      contribute to rotator cuff tendinopathy. The effects of scapular taping on the
      SAS in athletes with and without RC tendinopathy is unknown. OBJECTIVES: To
      investigate the immediate effects of scapular taping on the SAS in athletes with
      and without RC tendinopathy. DESIGN: Randomized-controlled with repeated
      measures. SETTING: University laboratory. PARTICIPANTS: Forty-three male
      volleyball players (17 asymptomatic and 26 with RC tendinopathy, mean age =
      22.9+/-3.5 years) participated in the study. INTERVENTION: Three scapular taping
      protocols - no taping (control), taping with tension (therapeutic taping) and
      taping without tension (sham taping). MAIN OUTCOME MEASURES: Ultrasound
      measurements of the SAS with the arm at 0 degrees  and 60 degrees  of shoulder
      abduction, and the change in the SAS between 0 degrees  and 60 degrees  of
      shoulder abduction (SAS0 degrees -60 degrees ) were calculated. RESULTS: Athletes
      with RC tendinopathy demonstrated larger SAS with therapeutic taping at 60
      degrees  of shoulder abduction (6.9+/-1.9 mm vs. 5.8+/-1.7 mm, mean difference =
      1.1 mm, 95% CI = -1.80 - -0.39, p=0.002) when compared to the no taping
      condition. The tendinopathy group also showed less reduction in the SAS with
      therapeutic taping during SAS0 degrees -60 degrees  (2.0+/-1.4 mm vs. 2.8+/-1.4
      mm, p=0.023) when compared to the no taping condition. When tape was applied to
      the scapula in asymptomatic athletes, our results showed a relatively small
      increase in the SAS with therapeutic taping during arm resting at 0 degrees  of
      abduction when compared to the no taping condition (8.7+/-0.9 mm vs. 8.3+/-0.8
      mm, mean difference = 0.4 mm, 95% CI = -0.71 - -0.11, p=0.008). CONCLUSIONS:
      Athletes with RC tendinopathy demonstrated less reduction of the SAS with rigid
      scapular taping during early arm abduction. Such observation was not evidenced in
      asymptomatic athletes.

PMID- 29466077
TI  - Do People Inherently Dislike Uncertain Advice?
AB  - Research suggests that people prefer confident to uncertain advisors. But do
      people dislike uncertain advice itself? In 11 studies ( N = 4,806), participants
      forecasted an uncertain event after receiving advice and then rated the quality
      of the advice (Studies 1-7, S1, and S2) or chose between two advisors (Studies 8
      9). Replicating previous research, our results showed that confident advisors
      were judged more favorably than advisors who were "not sure." Importantly,
      however, participants were not more likely to prefer certain advice: They did not
      dislike advisors who expressed uncertainty by providing ranges of outcomes,
      giving numerical probabilities, or saying that one event is "more likely" than
      another. Additionally, when faced with an explicit choice, participants were more
      likely to choose an advisor who provided uncertain advice over an advisor who
      provided certain advice. Our findings suggest that people do not inherently
      dislike uncertain advice. Advisors benefit from expressing themselves with
      confidence, but not from communicating false certainty.

PMID- 29466078
TI  - Recovery of Cycling Gross Efficiency After Time-Trial Exercise.
AB  - BACKGROUND: Research has shown that gross efficiency (GE) declines during high
      intensity exercise, but the time course of recovery of GE after high-intensity
      exercise has not yet been investigated. PURPOSE: To determine the time course of
      the recovery of GE after time trials (TTs) of different lengths. METHODS:
      Nineteen trained male cyclists participated in this study. Before and after TTs
      of 2000 and 20,000 m, subjects performed submaximal exercise at 55% of the power
      output attained at maximal oxygen uptake (PVO2max). The postmeasurement continued
      until 30 min after the end of the TT, during which GE was determined over 3-min
      intervals. The magnitude-based-inferences approach was used for statistical
      analysis. RESULTS: GE decreased substantially during the 2000-m and 20,000-m TTs
      (-11.8% [3.6%] and -6.2% [4.0%], respectively). A most likely and very likely
      recovery of GE was found during the first half of the submaximal exercise bout
      performed after the 2000-m, with only a possible increase in GE during the first
      part of the submaximal exercise bout performed after the 20,000-m. After both
      distances, GE did not fully recover to the initial pre-TT values, as the
      difference between the pre-TT value and average GE value of minutes 26-29 was
      still most likely negative for both the 2000- and 20,000-m (-6.1% [2.8%] and 
      7.0% [4.5%], respectively). CONCLUSIONS: It is impossible to fully recover GE
      after TTs of 2000- or 20,000-m during 30 min of submaximal cycling exercise
      performed at an intensity of 55% PVO2max.

PMID- 29466079
TI  - Reduced Fatigue in Passive Versus Active Recovery: An Examination of Repeated
      Change-of-Direction Sprints in Basketball Players.
AB  - PURPOSE: To investigate the physiological and performance effects of active and
      passive recovery between repeated-change-of-direction sprints. METHODS: Eight
      semiprofessional basketball players (age: 19.9 [1.5] y; stature: 183.0 [9.6] cm;
      body mass: 77.7 [16.9] kg; body fat: 11.8% [6.3%]; and peak oxygen consumption:
      46.1 [7.6] mL.kg-1.min-1) completed 12 * 20-m repeated-change-of-direction
      sprints (Agility 5-0-5 tests) interspersed with 20 seconds of active (50% maximal
      aerobic speed) or passive recovery in a randomized crossover design.
      Physiological and perceptual measures included heart rate, oxygen consumption,
      blood lactate concentration, and rating of perceived exertion. Change-of
      direction speed was measured during each sprint using the change-of-direction
      deficit (CODD), with summed CODD time and CODD decrement calculated as
      performance measures. RESULTS: Average heart rate (7.3 [6.4] beats.min-1; P =
      .010; effect size (ES) = 1.09; very likely) and oxygen consumption (4.4 [5.0]
      mL.kg-1.min-1; P = .12; ES = 0.77; unclear) were moderately greater with active
      recovery compared with passive recovery across sprints. Summed CODD time (0.87
      [1.01] s; P = .07; ES = 0.76, moderate; likely) and CODD decrement (8.1% [3.7%];
      P < .01; ES = 1.94, large; almost certainly) were higher with active compared
      with passive recovery. Trivial-small differences were evident for rating of
      perceived exertion (P = .516; ES = 0.19; unclear) and posttest blood lactate
      concentration (P = .29; ES = 0.40; unclear) between recovery modes. CONCLUSIONS:
      Passive recovery between repeated-change-of-direction sprints may reduce the
      physiological stress and fatigue encountered compared with active recovery in
      basketball players.

PMID- 29466080
TI  - Does Pre-Cooling With Whole-Body Immersion Affect Thermal Sensation or Perceived
      Exertion?: A Critically-Appraised Topic.
AB  - : Clinical Scenario: Exertional heat stroke (EHS) is a potentially deadly heat
      illness and poses a significant health risk to athletes; EHS survival rates are
      near 100% if properly recognized and treated.1 Whole body cold water immersion
      (CWI) is the most effective method of lowering body core temperature.2 Precooling
      (PC) with CWI before exercise may prevent severe hyperthermia and/or EHS by
      increasing the body's overall heat-storage capacity.3 However, PC may also alter
      athletes' perception of how hot they feel or how hard they are exercising.
      Consequently, they may be unable to accurately perceive their body core
      temperature or how hard they are working which may predispose them to severe
      hyperthermia or EHS. CLINICAL QUESTION: Does PC with whole-body CWI affect
      thermal sensation (TS) or rating of perceived exertion (RPE) during exercise in
      the heat? SUMMARY OF FINDINGS: In four studies,4-7 RPE during exercise ranged
      from 12 +/- 2 to 20 +/- 3 with no clinically meaningful differences between PC
      and control trials. Thermal sensation scores ranged from 2 +/- 1 to 8 +/- 0.5 in
      control trials and from 2 +/- 1 to 7.5 +/- 0.5 during PC trials. Clinical Bottom
      Line: Precooling did not cause clinically-meaningful differences in RPE or TS
      during exercise. It is unlikely PC would predispose athletes to EHS by altering
      perceptions of exercise intensity or body core temperature. Strength of
      Recommendation: None of the reviewed studies4-7 (all level 2 studies with PEDro
      scores >=5) suggest PC with CWI influences RPE or TS in exercising males.

PMID- 29466081
TI  - Kinesio Taping Improves Perceptions of Pain and Function of Patients with Knee
      Osteoarthritis. A Randomized, Controlled Trial.
AB  - CONTEXT: Although increasingly used for therapeutic treatment only limited
      evidence exists regarding the effects of kinesio taping on patients with knee
      osteoarthritis. OBJECTIVE: To determine the effects of kinesio taping on pain,
      function, gait and neuromuscular control concerning patients with knee
      osteoarthritis (OA). DESIGN: Randomized sham-controlled trial. SETTING:
      University laboratory. PARTICIPANTS: 141 Patients (65.1+/-7.0 years) with a
      clinical and radiographic diagnosis of knee osteoarthritis. INTERVENTION: Kinesio
      tape, sham tape or no tape for 3 consecutive days. MAIN OUTCOME MEASURES: Self
      reported pain, stiffness and function were measured by the Western Ontario and
      McMaster Universities Arthritis Index (WOMAC). Further tests included the Balance
      Error Scoring System (BESS-Test), 10-m Walk Test (10MWT), the maximum voluntary
      isometric contraction force (MVIC) of the quadriceps femoris and knee active
      range of motion (active ROM). RESULTS: At baseline, there were no differences in
      all outcomes between groups except for knee flexion. Significant effects were
      found for WOMAC pain (tape vs. sham p=0.053; tape vs. control p=0.047), stiffness
      (tape vs. sham p=0.012; tape vs. control p<=0.001) and physical function (tape
      vs. sham p=0.034; tape vs. control p=0.004). No interactions were found for
      balance, muscle strength, walking speed or active ROM. CONCLUSION: Wearing
      kinesio tape for three consecutive days had beneficial effects regarding self
      reported clinical outcomes of pain, joint stiffness and function. This emphasizes
      that kinesio taping might be an adequate conservative treatment for the symptoms
      of knee osteoarthritis.

PMID- 29466082
TI  - Determination of Optimum Operation Parameters for Low-Intensity Pulsed Ultrasound
      and Low-Level Laser Based Treatment to Induce Proliferation of Osteoblast and
      Fibroblast Cells.
AB  - OBJECTIVE: The aim of this study was to determine the optimum operating
      parameters (pulse duration, energy levels, and application time) to promote
      induction of osteoblast and fibroblast cell proliferation and to maintain cell
      viability treated with low-intensity pulsed ultrasound (LIPUS) and low-level
      laser therapy (LLLT). BACKGROUND DATA: The positive effects of LIPUS and LLLT on
      cellular activity have been reported in recent years. Comparisons between
      experimental parameters of previous studies are difficult because scientific
      studies reported frequencies and the duty cycles of LIPUS and wavelengths and
      doses of LLLT in a wide range of parameters. However, optimum amount of energy
      and optimum time exposure must be determined to induce bone and tissue cell
      proliferation for effective healing process and to avoid cell damage. MATERIAL
      AND METHODS: Fibroblast and osteoblast cell cultures were irradiated with LIPUS
      (10-50% pulse and continuous mode at 1 and 3 MHz for 1, 3, and 5 min) and LLLT
      (4, 8, and 16 J at 50, 100, 200, 300, 400, and 500 mW). Cell cultures were
      analyzed using XTT assay. RESULTS: For both cell types, LIPUS treatment with 10%
      pulse (1:9 duty cycle), 3 MHz, and for 1 min and LLLT treatment over 100 mV for
      4, 8, and 16 J modalities contributed to the growth, and may help bone repair and
      tissue healing process optimally. CONCLUSIONS: Bio-stimulating effects of LLLT
      irradiation promote proliferation and maintain cell viability better than LIPUS
      treatment without causing thermal response for both cell types, and the
      therapeutic modality above 200 mV has maximum effectiveness.

PMID- 29466083
TI  - Laparoscopic Nissen Fundoplication: An Excellent Treatment of GERD-Related
      Respiratory Symptoms in Children-Results of a Multicentric Study.
AB  - INTRODUCTION: Respiratory manifestations of gastroesophageal reflux disease
      (GERD), particularly chronic cough, are being recognized with increased frequency
      in children. This survey aimed to investigate the efficacy of laparoscopic Nissen
      fundoplication for treatment of GERD-related respiratory symptoms not responsive
      to medical therapy in neurological normal children. MATERIALS AND METHODS: We
      collected data of children with GERD-related respiratory complaints not
      responsive to medical therapy who underwent laparoscopic Nissen fundoplication in
      four European centers of Pediatric Surgery over a 10-year period. We excluded
      children with neurological impairment. RESULTS: A total of 220 laparoscopic
      Nissen procedures were performed in the period 2005-2015. Twenty-four (12 boys
      and 12 girls, average age 9.5 years) out of the 220 patients (10.9%) presented
      with chronic cough and other respiratory manifestations, including asthma,
      reactive airway disease, and recurrent pneumonia. Average operative time was 65
      minutes (range 45-100). As for postoperative complications, two tight wraps
      requiring endoscopic dilatation (IIIb Clavien) and two relapses of GERD for
      slipped Nissen requiring reoperation (IIIb Clavien) were recorded. None of these
      complications occurred in the group of patients with GERD-related respiratory
      symptoms. At follow-up evaluation, respiratory symptoms disappeared with a
      significant improvement of quality of life scoring (I Grade Visick) in 22/24
      patients (91.6%). CONCLUSION: Our results confirm that GERD should be
      investigated as one of the possible etiologic factors in any child with
      persistent respiratory complaints. In patients with symptoms not responsive to
      medical therapy, laparoscopic Nissen fundoplication is the treatment of choice
      with a very high success rate (>90% in our series), a very low morbidity, a
      significant improvement in airway symptoms, and a marked reduction in the need
      for medications.

PMID- 29466084
TI  - Fertility-Related Perceptions and Impact on Romantic Relationships Among Adult
      Survivors of Childhood Cancer.
AB  - PURPOSE: To present an overview of fertility-related perceptions and describe the
      perceived negative/positive impact of (potential) infertility on romantic
      relationships among childhood cancer survivors. METHODS: Male and female long
      term childhood cancer survivors (N = 92) aged 22-43 and 7-37 years postdiagnosis,
      completed an online survey about fertility-related perceptions (i.e., knowledge,
      beliefs, uncertainty, concern, and attitudes toward testing) and romantic
      relationships. Potential differences based on sociodemographic/cancer-specific
      factors were tested. RESULTS: Most survivors (82.4%, n = 75) knew about
      infertility risk due to childhood cancer treatment. Seventy percent (n = 65)
      reported being told they were personally at risk, but less than one-third
      believed it (29.2%, n = 19/65). Half of survivors (48.9%, n = 45) never underwent
      fertility testing and were unaware of their fertility status. Fertility-related
      uncertainty and concerns were more common among survivors without children and
      those who desired (additional) children (d's > 0.5). Among survivors without
      biological children (n = 52), partnered survivors felt more uncertain about their
      fertility than singles (d = 0.8). Ten survivors (10.9%) reported a negative
      impact of infertility on romantic relationships, 6 (6.5%) reported a positive
      impact, and 7 (7.6%) reported both (e.g., pressure on relationship, fights, break
      ups, being closer, and open partner communication). CONCLUSIONS: Fertility
      related perceptions varied among survivors, but the majority never underwent
      fertility testing. Uncertainty or concerns differed by current circumstances
      (e.g., wanting children and relationship status). Providers should routinely
      discuss potential infertility and offer testing throughout survivorship. A
      negative impact on romantic relationships may seem small, but should be
      considered for survivors who desire children and may discover they are infertile
      in the future.

PMID- 29466085
TI  - A case of HIV associated cryptococcal nephritis: Ultrastructural findings and
      literature review.
AB  - Acute renal failure in the setting of infection with human immunodeficiency virus
      can be due to various causes including pre-renal causes such as hypotension,
      sepsis, and nephrotoxic agents; thrombotic microangiopathy; or direct renal
      parenchymal infections by opportunistic organisms. We present a case of
      cryptococcal nephritis in a patient with systemic cryptococcosis and discuss the
      clinical findings as well as the histological, immunofluorescent, and
      transmission electron microscopy findings in the renal biopsy.

PMID- 29466086
TI  - Vulnerability of glia and vessels of rat substantia nigra in rotenone Parkinson
      model.
AB  - BACKGROUND: Astrocytes have been implicated as potentially exerting both
      neurotoxic and neuroprotective activities in Parkinson's disease (PD). Whether
      glial cells negatively impact the neuron integrity remains to be determined. We
      aimed to assess the vulnerability of glia and vessels in rat substantia nigra in
      a rotenone PD model. MATERIAL AND METHODS: Twenty adult male albino rats were
      divided into two equal groups: vehicle-control group (received dimethylsulfoxide
      + polyethylene glycol (PEG)-300, 1:1 v/v) and rotenone-treated group (received
      six doses of rotenone, 1.5 mg/kg/48 h s.c.). Using histological, ultrastructural,
      biochemical, and morphometric techniques, astrocytes, microglia, vessels, and
      total antioxidant capacity have been assessed. RESULTS: The rotenone-treated
      group revealed an increase in the number of astrocytes compared to the control,
      conformational changes of the immature form, disruption of the outer
      mitochondrial membrane, and no increase in glial filaments. Dark microglia
      appeared in close vicinity of blood capillaries. The blood capillaries displayed
      an increase in number compared to the control, degenerated apoptotic endothelium,
      and pericytes and an increase in string vessels. The total antioxidant level
      significantly increased in rotenone-treated group (p < 0.001) compared to the
      control group. CONCLUSION: Our results demonstrated that oxidative stress and
      mitochondrial dysfunction involved nigral cellular elements other than
      dopaminergic neurons. These included astrocytes, microglia, vascular endothelial
      cells, and pericytes, which might result in promoting damage to the neurons.

PMID- 29466087
TI  - Rat hippocampal CA3 neuronal injury induced by limb ischemia/reperfusion: A
      possible restorative effect of alpha lipoic acid.
AB  - Limb ischemia reperfusion (I/R) injury is associated with serious local and
      systemic effects. Reperfusion may augment tissue injury in excess of that
      produced by ischemia alone. The hippocampus has been reported to be vulnerable to
      I/R injury. Alpha lipoic acid (ALA) is an endogenous antioxidant with a powerful
      antioxidative, anti-inflammatory, and antiapoptotic properties. We studied the
      probable restorative effect of ALA on limb I/R-induced structural damage of rat
      hippocampus. Forty adult male albino rats were divided equally into four groups:
      group I (sham); group II (I/R-1 day) has undergone bilateral femoral arteries
      occlusion (3 h), then reperfusion for 1 day; group III (I/R-7 days) has undergone
      reperfusion for seven days; group IV (I/R-ALA) has undergone I/R as group III and
      received an intraperitoneal injection of ALA (100 mg/kg) for 7 days. I/R groups
      revealed degenerative changes in the pyramidal neuronal perikarya of CA3 field in
      the form of dark-stained cytoplasm, dilated RER cisternae, mitochondrial
      alterations, and dense bodies' accumulation. Their dendrites showed disorganized
      microtubules. Astrogliosis is featured by an increased number and increased
      immunoreactivity of astrocytes for glial fibrillary acid protein. Morphometric
      data revealed significant reduction of light neurons, surface area of neurons,
      and thickness of the CA3 layer. Most blood capillaries exhibited narrow lumen and
      irregular basal lamina. ALA ameliorated the neuronal damage. Pyramidal neurons
      revealed preservation of normal structure. Significant increase in the thickness
      of pyramidal layer in CA3 field and surface area and number of light neurons was
      observed but astrogliosis persisted. Limb I/R had a deleterious remote effect on
      the hippocampus aggravated with longer period of reperfusion. This work may
      encourage the use of ALA in the critical clinical settings with I/R injury.

PMID- 29466088
TI  - Crotamine-like from Southern Pacific rattlesnake (Crotalus oreganus helleri)
      Venom acts on human leukemia (K-562) cell lines and produces ultrastructural
      changes on mice adrenal gland.
AB  - Crotamine is a cationic, non-enzymatic, protein integrating a minor family of
      myotoxins, composed of 42 amino acid residues, described in Viperidae and
      Crotalidae snake's families that has been used in neuroscience research, drug
      progressing and molecular diversity reports. Crotamine-like protein (CLP) from
      C.o.helleri venom was isolated in fraction 5 from 7 peaks obtained by sulfopropyl
      waters protein pak cationic exchange column. In tricine-SDS-PAGE under non
      reduced conditions this CLP showed a single band of ~8 kDa molecular weight. CLP
      induced toxicity of K-562 cells with a CC50 of 11.09 uM. In mice adrenal gland
      after 24 h of CLP injection, cortical cells exhibited swollen mitochondria with
      scarce tubular cristae, some elements of smooth and rough endoplasmic reticula,
      widened nuclear envelope, slightly osmiophilic lipid droplets, and autophagic
      vacuoles. In some areas cortical cells plasma membrane and endothelial walls
      disappeared, which indicated a necrosis process. In other areas, endothelial cell
      cytoplasm did not present the normal caveolae and pinocytotic vesicles. To our
      knowledge, this is the first report on mice adrenal gland damages, caused by the
      injection of CLP from rattlesnakes. Our results propose that adrenal cortex
      lesions may be significant in the envenoming etiopathogenesis by CLP.

PMID- 29466089
TI  - Photobiomodulation and Cancer: What Is the Truth?
AB  - BACKGROUND: Photobiomodulation (PBM) therapy is a rapidly growing approach to
      stimulate healing, reduce pain, increase athletic performance, and improve
      general wellness. OBJECTIVE: Applying PBM therapy over the site of a tumor has
      been considered to be a contraindication. However, since another growing use of
      PBM therapy is to mitigate the side effects of cancer therapy, this short review
      seeks to critically examine the evidence of whether PBM therapy is beneficial or
      harmful in cancer patients. MATERIALS AND METHODS: PubMed and Google Scholar were
      searched. RESULTS: Although there are a few articles suggesting that PBM therapy
      can be detrimental in animal models of tumors, there are also many articles that
      suggest the opposite and that light can directly damage the tumor, can potentiate
      other cancer therapies, and can stimulate the host immune system. Moreover, there
      are two clinical trials showing increased survival in cancer patients who
      received PBM therapy. CONCLUSIONS: PBM therapy may have benefits in cancer
      patients and should be further investigated.

PMID- 29466090
TI  - Enhanced External Counterpulsation and Short-Term Recovery From High-Intensity
      Interval Training.
AB  - PURPOSE: Enhanced external counterpulsation (EECP) is a recovery strategy whose
      use has increased in recent years owing to the benefits observed in the clinical
      setting in some cardiovascular diseases (ie, improvement of cardiovascular
      function). However, its claimed effectiveness for the enhancement of exercise
      recovery has not been analyzed in athletes. The aim of this study was to
      determine the effectiveness of EECP on short-term recovery after a fatiguing
      exercise bout. METHODS: Twelve elite junior triathletes (16 [2] y) participated
      in this crossover counterbalanced study. After a high-intensity interval training
      session (6 bouts of 3-min duration at maximal intensity interspersed with 3-min
      rest periods), participants were assigned to recover during 30 min with EECP (80
      mm Hg) or sham (0 mm Hg). Measures of recovery included performance (jump height
      and mean power during an 8-min time trial), metabolic (blood lactate
      concentration at several time points), autonomic (heart-rate variability at
      several time points), and subjective (rating of perceived exertion [RPE] and
      readiness to compete) outcomes. RESULTS: There were no differences between EECP
      and sham in mean RPE or power output during the high-intensity interval training
      session, which elicited a significant performance impairment, vagal withdrawal,
      and increased blood lactate and RPE in both EECP and sham conditions (all P <
      .05). No significant differences were found in performance, metabolic, or
      subjective outcomes between conditions at any time point. A significantly lower
      high-frequency power (P < .05, effect size = 1.06), a marker of parasympathetic
      activity, was observed with EECP at the end of the recovery phase. CONCLUSION:
      EECP did not enhance short-term recovery after a high-intensity interval training
      session in healthy, highly trained individuals.

PMID- 29466091
TI  - Infections by Hepatic Trematodes in Cats from Slaughterhouses in Vietnam.
AB  - Domestic cats are a final host for some hepatic trematodes, and cat meat is used
      for human consumption in several parts of northern Vietnam. Since there is no
      tradition for commercial cat rearing in the area, cats are purchased alive from
      other areas as well, i.e., southern Vietnam and neighboring countries, and
      brought to slaughterhouses. This uncontrolled trade in live cats could pose a
      risk for spread of various parasites, including hepatic trematodes. Hence, in
      this study, we investigated the infections by hepatic trematodes in cats from the
      slaughterhouses. Cat livers were sampled from 12 slaughterhouses. Clonorchis
      sinensis and Platynosomum fastosum were found in 14 of 78 necropsied cats of
      local origin, while more than half of the non-local cats (170 of 318) were
      infected by C. sinensis, P. fastosum, or Opisthorchis viverrini. The non-local
      cats had higher prevalence (odds ratio = 6.61, P < 0.01, 95% CI: 2.34-19.41) and
      intensity of infection (count ratio = 6.47, P < 0.01, 95% CI: 1.77-23.59) by C.
      sinensis than local cats. Prevalence of P. fastosum infection did not differ
      significantly between the 2 groups of cats. Opisthorchis viverrini was found at
      low prevalence (2.5%) in non-local cats. The presence of O. viverrini in cats
      sampled in northern Vietnam and the high prevalence and intensity of infection in
      cats of non-local origin suggest that cats are transported over great distances,
      and this poses a risk of spreading these trematodes.

PMID- 29466092
TI  - Initial Inoculation Concentration Does Not Affect Final Bacterial Colonization of
      In vitro Vascular Conduits.
AB  - BACKGROUND: Despite improved peri-operative care, prosthetic graft infections
      continue to cause substantial morbidity and mortality. Contemporary graft
      infection models have tested a conduit's infectability using varying
      concentrations without standardization. Using a static assay in vitro model, we
      sought to evaluate the impact of inoculation concentration on vascular conduit
      attachment. METHODS: The 2-hour and 24-hour attachment of Staphylococcus aureus
      TCH1516 and Pseudomonas aeruginosa PA01-UW were determined on
      polytetrafluoroethylene (PTFE), Dacron(r), nitinol, cobalt chromium, and
      Viabahn(r) (W.L. Gore and Associates, Newark, DE) endoprotheses. Individually and
      in combination, concentrations at 104, 105, 106, 107, and 108 were tested on 2-mm
      sections of each graft. After each time interval, the prosthetics were rinsed to
      remove non-attached bacteria, sonicated to release the attached bacteria, spiral
      plated, and then analyzed for the attached concentration. RESULTS: After two
      hours, the higher initial inoculation concentration translated into a higher
      attachment percentage, but the mean attachment percentage was only 14.8% in the
      108 group. Pseudomonas aeruginosa had the greatest mean attachment across all
      material and concentration groups. The sequence of attachment on the conduits
      followed a constant order: Dacron, PTFE, cobalt, nitinol, and Viabahn with no
      difference between Dacron and PTFE. Although there were still differences at the
      24-hour mark, the median attachment at each concentration was greater than the
      highest initial concentration (108). CONCLUSIONS: Initial attachment percentage
      is poor consistently regardless of inoculation concentration, however,
      Staphylococcus aureus and Pseudomonas aeruginosa are still able to achieve full
      attachment after 24 hours. A concentration of less than 107 should be used in
      vascular graft infection models to ensure adequate bacterial attachment.

PMID- 29466093
TI  - Efficacy of a Web-Based Tailored Intervention to Reduce Cannabis Use Among Young
      People Attending Adult Education Centers in Quebec.
AB  - BACKGROUND: Cannabis use is common among young adults. Web-based interventions
      are an increasingly popular way to reach this population. The aim of this study
      was to evaluate the efficacy of a Web-based tailored intervention, developed on
      theoretical and empirical grounds, to reduce cannabis use among young people by
      promoting a more positive intention to abstain. METHODS: An experimental design
      was employed to evaluate the efficacy of the intervention in reducing cannabis
      use (primary outcome) by bolstering intention (secondary outcome) to abstain from
      use. Participants were randomly assigned either to an experimental group that
      received the Web-based tailored intervention or to a control group that did not.
      RESULTS: Of 588 young adults (18-24 years of age) recruited, 295 were randomly
      assigned to the experimental group and 293 to the control group. At baseline, 343
      reported using cannabis at least once in the past year. An intention-to-treat
      analysis showed that, at postintervention, a higher proportion of participants in
      the experimental group had reduced their cannabis use compared with the control
      group [10.8% vs. 5.1%, chi2(2) = 9.89, p = 0.007]. A mixed model for repeated
      measures revealed a statistically significant difference in terms of change in
      intention to abstain from cannabis use in the coming month [Group * Time
      interaction, F(1,474) = 8.03, p = 0.005]: intention increased for the
      experimental group (5.07 +/- 2.07 to 5.45 +/- 1.88; p < 0.001), but stayed stable
      for the control group (5.32 +/- 2.03 to 5.36 +/- 1.99; p = 0.779). CONCLUSION:
      This study shows that the intervention can be efficacious in reducing cannabis
      use among young people attending adult education centers.

PMID- 29466094
TI  - Communication rights: Fundamental human rights for all.
AB  - The right to communicate includes the right to "freedom of opinion and
      expression" and rights and freedoms "without distinction of ... language". The
      70th anniversary of the Universal Declaration of Human Rights is a time to
      celebrate and reflect on communication as a human right, particularly with
      respect to Article 19 and its relationship to national and international
      conventions, declarations, policies and practices. This review profiles articles
      from the special issue of International Journal of Speech-Language Pathology
      (volume 20, issue 1) addressing communication rights from four perspectives: (1)
      communication rights of all people; (2) communication rights of people with
      communication disabilities; (3) communication rights of children and (4)
      communication rights relating to language. Divergent perspectives from across the
      globe are considered. First-hand accounts of people whose right to communicate is
      compromised/upheld are included and perspectives are provided from people with
      expertise and advocacy roles in speech-language pathology, audiology,
      linguistics, education, media, literature and law, including members of the
      International Communication Project. Three steps are outlined to support
      communication rights: acknowledge people - adjust the communication style - take
      time to listen. Future advocacy for communication rights could be informed by
      replicating processes used to generate the Yogyakarta Principles.

PMID- 29466095
TI  - The importance of the human right to communication.

PMID- 29466096
TI  - Measurement accuracy: Enabling human rights for Fijian students with speech
      difficulties.
AB  - PURPOSE: The Universal Declaration of Human Rights enshrines the rights to
      communication and education and measuring access to these rights for children
      with disabilities is fundamental. The UNICEF/Washington Group Child Functioning
      Module (CFM) is being promoted to measure progress against the Sustainable
      Development Goals for children with disabilities. This cross-sectional diagnostic
      accuracy study in Fiji compares parent and teacher CFM responses to the
      Intelligibility in Context Scale for 463 primary-aged students with and without
      speech difficulties. METHOD: Receiver operating characteristic curves were
      constructed to analyse CFM accuracy and determine optimal cut-off points; inter
      rater reliability between teachers and parents was calculated. RESULT: Parent
      responses to the CFM speech questions achieved an area under the curve of 0.98,
      indicating "excellent" diagnostic accuracy. Teachers achieved 0.92 ("very good").
      The Youden Index identified the optimal cut-off as "some difficulty". CONCLUSION:
      The CFM appears effective when used by parents or teachers for distinguishing
      between children with and without speech difficulties. While identified as the
      optimal cut-off statistically, the "some difficulty" category identifies too many
      children without speech difficulties to be simplistically applied to funding
      eligibility. The CFM should be used as a screening tool, followed by further
      assessment to confirm eligibility.

PMID- 29466097
TI  - A Clinical Decision Support System for Diabetic Retinopathy Screening: Creating a
      Clinical Support Application.
AB  - BACKGROUND: The aim of this study was to build a clinical decision support system
      (CDSS) in diabetic retinopathy (DR), based on type 2 diabetes mellitus (DM)
      patients. METHOD: We built a CDSS from a sample of 2,323 patients, divided into a
      training set of 1,212 patients, and a testing set of 1,111 patients. The CDSS is
      based on a fuzzy random forest, which is a set of fuzzy decision trees. A fuzzy
      decision tree is a hierarchical data structure that classifies a patient into
      several classes to some level, depending on the values that the patient presents
      in the attributes related to the DR risk factors. Each node of the tree is an
      attribute, and each branch of the node is related to a possible value of the
      attribute. The leaves of the tree link the patient to a particular class (DR, no
      DR). RESULTS: A CDSS was built with 200 trees in the forest and three variables
      at each node. Accuracy of the CDSS was 80.76%, sensitivity was 80.67%, and
      specificity was 85.96%. Applied variables were current age, gender, DM duration
      and treatment, arterial hypertension, body mass index, HbA1c, estimated
      glomerular filtration rate, and microalbuminuria. DISCUSSION: Some studies
      concluded that screening every 3 years was cost effective, but did not
      personalize risk factors. In this study, the random forest test using fuzzy rules
      permit us to build a personalized CDSS. CONCLUSIONS: We have developed a CDSS
      that can help in screening diabetic retinopathy programmes, despite our results
      more testing is essential.

PMID- 29466098
TI  - Comparing Global Positioning System and Global Navigation Satellite System
      Measures of Team-Sport Movements.
AB  - PURPOSE: To compare data from conventional global positioning system (GPS-) and
      new global navigation satellite system (GNSS-) enabled tracking devices and to
      examine the interunit reliability of GNSS devices. METHODS: Interdevice
      differences between 10-Hz GPS and GNSS devices were examined during laps (n = 40)
      of a simulated game circuit and during elite hockey matches (n = 21); GNSS
      interunit reliability was also examined during laps of the simulated game
      circuit. Differences in distance values and measures in 3 velocity categories
      (low <3 m.s-1; moderate 3-5 m.s-1; and high >5 m.s-1) and
      acceleration/deceleration counts (>1.46 and <-1.46 m.s-2) were examined using 1
      way analysis of variance. Interunit GNSS reliability was examined using the
      coefficient of variation (CV) and intraclass correlation coefficient. RESULTS:
      Interdevice differences (P < .05) were found for measures of peak deceleration,
      low-speed distance, percentage of total distance at low speed, and deceleration
      count during the simulated game circuit and for all measures except total
      distance and low-speed distance during hockey matches. Interunit (GNSS)
      differences (P < .05) were not found. The coefficient of variation was below 5%
      for total distance, average and peak speeds and distance and percentage of total
      distance of low-speed running. The GNSS devices had a lower horizontal dilution
      of precision score than GPS devices in all conditions. CONCLUSIONS: These
      findings suggest that GNSS devices may be more sensitive than GPS devices in
      quantifying the physical demands of team-sport movements, but further study into
      the accuracy of GNSS devices is required.

PMID- 29466099
TI  - Infrared Laser Improves Collagen Organization in Muscle and Tendon Tissue During
      the Process of Compensatory Overload.
AB  - BACKGROUND: The photobiomodulation using the low-level laser therapy (LLLT)
      exerts a positive modulating effect on the synthesis of collagen in skeletal
      muscles and tendons. However, few studies have addressed this effect during the
      compensatory overload. OBJECTIVE: Evaluate the effect of infrared laser on the
      deposition and organization of collagen fibers in muscle and tendon tissue during
      compensatory overload of the plantar muscle in rats. MATERIALS AND METHODS:
      Wistar rats were submitted to bilateral ablation of the synergist muscles of the
      hind paws and divided in groups: Control, Hypertrophy, and Hypertrophy (H)+LLLT
      (780 nm, 40 mW, 9.6 J/cm2 and 10 s/point, 8 points, total energy 3.2 J, daily),
      evaluated at 7 and 14 days. Muscle cuts were stained with Picrosirius-Red and
      hematoxylin-eosin and tendon cuts were submitted to birefringence for
      determination of collagen distribution and organization. RESULTS: After 7 days an
      increase was observed in the area between beam muscles in H+LLLT (25.45% +/-
      2.56) in comparison to H (20.3% +/- 3.31), in mature fibers and fibrilis in
      H+LLLT (29346.88 MUm2 +/- 2182.56; 47602.8 MUm2 +/- 2201.86 respectively) in
      comparison to H (26656.5 MUm2 +/- 1880.46; 45630.34 MUm2 +/- 2805.82
      respectively) and in the collagen area in H+LLLT (2.25% +/- 0.19) in comparison
      to H (2.0% +/- 0.15). However, after 14 days a reduction was observed in the area
      between beam muscles in H+LLLT (13.88% +/- 2.54) in comparison to H (19.1% +/-
      2.61), in fibrils and mature fibers in H+LLLT (17174.1 MUm2 +/- 2563.82; 32634.04
      MUm2 +/- 1689.38 respectively) in comparison to H (55249.86 MUm2 +/- 1992.65;
      44318.36 MUm2 +/- 1759.57) and in the collagen area in H+LLLT (1.76% +/- 0.16) in
      comparison to H (2.09 +/- 0.27). A greater organization of collagen fibers in the
      tendon was observed after 7 and 14 days in H+LLLT groups. CONCLUSIONS: Infrared
      laser irradiation induces an improvement in collagen organization in tendons and
      a reduction in the total area of collagen in muscles during compensatory atrophy
      following the ablation of synergist muscles.

PMID- 29466100
TI  - Broken Hearts and Opened Eyes.

PMID- 29466101
TI  - Psychiatric Disorders and Disorders of Psychiatry.

PMID- 29466102
TI  - Prepare for the Surge of the Silver Tsunami: Learning About Working With the
      Aging Adult.

PMID- 29466103
TI  - Migration and Mental Health in Low- and Middle-Income Countries: A Systematic
      Review.
AB  - OBJECTIVE: Rural-to-urban migration within low- and middle-income countries
      (LMICs), and migration from one LMIC to another, are prevalent forms of
      international migration. Migration may be associated with adverse mental health
      outcomes. The aim of the current study is to systematically review the literature
      on migration and mental health between and within LMICs. METHODS: This systematic
      review of PubMed, PsycINFO, Embase, Web of Science, and PILOTS, identified 2,818
      total records published between 1991 and 2016, with 139 of these assessed for
      eligibility. Two authors reviewed full text to assess if they met inclusion
      criteria, extracted data, and applied a quality assessment to all included
      studies. RESULTS: The search identified 37 articles that met the inclusion
      criteria, based on 28 separate studies. All studies apart from one were cross
      sectional studies, and studies utilized a range of sampling methods. In all, 19
      of these studies were conducted in China. Studies addressed a range of mental
      health outcomes, and variation in prevalence was reported. Research questions
      addressed determinants of mental health outcomes, including analysis of risk and
      protective factors, such as social, cultural, and economic determinants;
      migration-related risk factors; and substance use. CONCLUSIONS: Limitations in
      study design and methodological rigor of studies indicate a limited evidence base
      concerning migration and mental health in LMICs. Expansion of research to
      different regions, utilization of adapted and validated measurement instruments,
      and longitudinal research could significantly strengthen the evidence base.

PMID- 29466104
TI  - Suicidality in High-Risk Psychiatric Patients: The Contribution of Protective
      Factors.
AB  - OBJECTIVE: This study's objective was determine the incremental association of
      reasons for living to the lifetime number of suicide attempts in relation to
      other known risk and protective factors in a sample of psychiatric patients with
      extensive psychopathology in residential treatment. METHODS: Participants (n =
      131) completed a demographic questionnaire that also asked for information about
      lifetime suicide history, psychiatric history, trauma, and abuse history.
      Additional measures of resilience, reasons for living (RFL), and impulsiveness
      were completed. RESULTS: A history of sexual abuse was associated with an
      increasing lifetime number of suicide attempts, while a history of physical abuse
      and trait impulsiveness were not associated with the lifetime number of suicide
      attempts. Survival and coping beliefs, a subscale of the Reasons for Living
      Inventory (RFLI), was found to add incremental predictive validity to the number
      of lifetime suicide attempts. A composite fear variable, combining fear of
      suicide and fear of social consequences of suicide, was negatively correlated
      with lifetime number of attempts but did not add incremental validity to the
      prediction of lifetime number of suicide attempts. CONCLUSION: In a sample of
      participants with significant psychiatric impairment, the protective factor of
      survival and coping beliefs may be an important barrier to repeated suicide
      attempts and may be considered a suicide-specific resilience measure.
      Understanding the psychological processes contributing to the development of such
      protective factors as resilience, meaning in life, and coping resources is an
      important area of study and a potential avenue for targeted therapeutic
      intervention in high-risk populations.

PMID- 29466105
TI  - Learning to Tolerate Not Knowing.

PMID- 29466106
TI  - Uncertainty Theory and Freud's Complemental Series.

PMID- 29466107
TI  - A Randomized Controlled Trial of the Collaborative Assessment and Management of
      Suicidality versus Enhanced Care as Usual With Suicidal Soldiers.
AB  - OBJECTIVE: This study describes a randomized controlled trial called "Operation
      Worth Living" (OWL) which compared the use of the Collaborative Assessment and
      Management of Suicidality (CAMS) to enhanced care as usual (E-CAU). We
      hypothesized that CAMS would be more effective than E-CAU for reducing suicidal
      ideation (SI) and suicide attempts (SA), along with secondary behavioral health
      and health care utilization markers for U.S. Army Soldier outpatients with
      significant SI (i.e., > 13 on Beck's Scale for Suicide Ideation). METHOD: Study
      participants were 148 Soldiers who presented to a military outpatient behavioral
      health clinic. There were 73 Soldiers in the experimental arm of the trial who
      received adherent CAMS; 75 Soldiers received E-CAU. Nine a-priori treatment
      outcomes (SI, past year SA, suicide-related emergency department (ED) admits,
      behavioral health-related ED admits, suicide-related inpatient psychiatric unit
      (IPU) days, behavioral health-related IPU days, mental health, psychiatric
      distress, resiliency) were measured through assessments at Baseline and at 1, 3,
      6, and 12 months post-Baseline (with a 78% retention of intent-to-treat
      participants at 12 months). RESULTS: Soldiers in both arms of the trial responded
      to study treatments in terms of all primary and secondary outcomes (effect sizes
      ranged from 0.63 to 12.04). CAMS participants were significantly less likely to
      have any suicidal thoughts by 3 months in comparison to those in E-CAU (Cohen's d
      = 0.93, p=.028). CONCLUSIONS: Soldiers receiving CAMS and E-CAU significantly
      improved post-treatment. Those who received CAMS were less likely to report SI at
      3 months; further group differences were not otherwise seen.

PMID- 29466108
TI  - Uncertainty as a Driver of Mental Disorder Diagnostic Strategies.

PMID- 29466109
TI  - Uncertainty Theory: A Powerful Approach to Understanding Psychiatric Disorder.
AB  - OBJECTIVE: The tendency over the years in the mental health field has been to
      cling in circular fashion to one single domain after another, biological,
      psychological, or social, to explain severe disorder and not even to consider the
      data from the domain of focus that came before. This report notes that attempts
      to explore more complex biopsychosocial explanations that integrate the diverse
      domains have been generally ignored or foundered on the problems posed by the
      complexities involved and suggests an approach for moving beyond these problems.
      METHOD: A case history using two different formats highlights the degree to which
      the single domain models ignore one or another area of data. RESULTS: Uncertainty
      theory is suggested as providing an important basis for exploring the
      complexities of a biopsychosocial understanding of mental health problems.
      CONCLUSIONS: This approach can provide a possible orientation to promote improved
      research, training, and treatment.

PMID- 29466110
TI  - Peritraumatic Reaction Courses During War in Individuals With Serious Mental
      Illness: Gender, Mental Health Status, and Exposure.
AB  - OBJECTIVE: We assessed in vivo symptom courses of early psychological responses
      during war and investigated the influence of exposure, gender, and a prior
      diagnosis of severe mental illness (SMI). METHOD: Participants were 181 highly
      exposed individuals from the general population and community psychiatric
      rehabilitation centers. A 30-day twice-daily Internet-smartphone-based intensive
      assessment two weeks into the 2014 Israel-Gaza war estimated peritraumatic
      symptom clusters, sense of threat, negative emotions and cognitions, and siren
      exposure during two periods that varied in exposure level. Piecewise growth curve
      modeling procedures were performed. RESULTS: We found different courses for most
      variables, gender, and SMI status. Women were more reactive two weeks into the
      war but reduced their reactivity level at a faster pace than males, reaching
      lower symptom levels one month later. Women's courses were characterized by
      arousal, negative emotionality, sense of threat, and reactivity to siren
      exposure. No-SMI men had a stable course followed by a significant reduction in
      arousal, negative emotions, avoidance, and perceived threat during a "return to
      routine" lower-level intensity period of the war. Individuals with SMI had higher
      reactivity levels at study onset; but while women with SMI improved over time,
      men with SMI worsened. SMI reactivity was characterized by negative cognitions,
      intrusions, and avoidance. CONCLUSIONS: Early reactions during prolonged exposure
      to war are variable, dynamic, and affected by exposure context. Symptoms,
      emotions, and cognitions develop differentially over time and are affected by
      gender and mental health status. The identification of various early stress
      courses should inform primary intervention strategies.

PMID- 29466112
TI  - On the Illusion of Certainty.

PMID- 29466111
TI  - Facilitating Fear-Based Memory Extinction With Dexamethasone: A Randomized
      Controlled Trial in Male Veterans With Combat-Related PTSD.
AB  - OBJECTIVE: Animal and preliminary human studies have demonstrated that
      glucocorticoids enhance the extinction of fear memories. Impaired extinction of
      fear memories is a critical component in the development and maintenance of
      posttraumatic stress disorder (PTSD). The purpose of this translational study was
      to determine the effectiveness of pairing a glucocorticoid with trauma memory
      reactivation as a novel intervention to treat PTSD and to measure the duration of
      the effect. METHOD: A total of 54 male veterans with combat-related PTSD in this
      double-blind, randomized, placebo-controlled trial received either four weekly
      glucocorticoid (dexamethasone [DEX]) or placebo administrations paired with a 45
      second trauma memory reactivation task. PTSD and depressive symptom severity were
      assessed at baseline and at one three, and six months. RESULTS: Trauma memory
      activation paired with DEX versus trauma memory activation paired with placebo
      demonstrated a significantly greater reduction of PTSD symptoms for DEX at the
      one-month (p = .037) and three-month (p = .036) posttreatment assessments, but
      the difference was no longer evident at six months. DEX showed a nonsignificantly
      greater reduction of PTSD symptoms than placebo over the course of the study (p =
      .067). Significantly more veterans in the DEX group lost their diagnosis of PTSD
      at one month posttreatment compared to the placebo group, but the difference was
      not maintained at three or six months. DEX had no effect on depression symptoms.
      CONCLUSIONS: Despite insufficient power to test differences in PTSD symptom
      reduction, findings suggest that this novel intervention may have potential for
      treatment of combat-related PTSD.

PMID- 29466113
TI  - Embracing Not-Knowing: Toward Narration and Humanism in Medicine.

PMID- 29466114
TI  - Organizing Knowledge in the Biopsychosocial Medical Model.

PMID- 29466115
TI  - Clinical Manual of Cultural Psychiatry.

PMID- 29466117
TI  - Childhood Maltreatment, Self-esteem, and Suicidal Ideation in a Low-SES Emerging
      Adult Sample: The Moderating Role of Heart Rate Variability.
AB  - Childhood maltreatment is associated with risk for suicidal ideation later in
      life, yet more research is needed on the indirect effects and bioregulatory
      protective factors in this association. The present study aimed to investigate
      the indirect influence of childhood maltreatment on suicidal ideation in emerging
      adulthood via level of self-esteem, and examine the moderating role of heart rate
      variability (HRV; a proxy for emotion regulation) in this indirect association.
      The study included a sample of 167 non-metropolitan emerging adults (Mage =
      21.17, 55.8% female) of low-socioeconomic status (low-SES). HRV data were obained
      using an electrocardigram, whereas childhood maltreatment, suicidal ideation, and
      self-esteem data were obtained via self-report. Childhood maltreatment was
      indirectly associated with suicidal ideation via reduced self-esteem. HRV
      buffered this indirect association. Childhood maltreatment poses a risk for the
      development of suicidal ideation. Interventions that bolster self-esteem and
      emotion regulation may reduce suicide risk for emerging adults with a history of
      childhood maltreatment.

PMID- 29466116
TI  - Acute Effects of Low-Level Laser Therapy on Patients' Functional Capacity in the
      Postoperative Period of Coronary Artery Bypass Graft Surgery: A Randomized,
      Crossover, Placebo-Controlled Trial.
AB  - OBJECTIVE: The aim of this study was to evaluate the acute effects of low-level
      laser therapy (LLLT) on the functional capacity to exercise tested by incremental
      shuttle walking test (ISWT) after coronary artery bypass graft (CABG) surgery.
      METHODS: Fifteen male patients (60 +/- 9 years) were crossed over during the
      experiment, to compare the outcomes after active LLLT and placebo LLLT
      treatments. LLLT (850 nm, 200 mW, 30 J to each point, resulting in a total of 240
      J per quadriceps muscle), using a multidiode cluster (five spots; 6 J/spot) in
      eight points per leg was performed 3 min before the ISWT. We analyzed distance
      walked, Borg scale of perceived exertion, heart rate, and brachial arterial blood
      pressure. Markers of tissue damage [lactate dehydrogenase (LDH)] and oxidative
      stress [lipid peroxidation, total thiol levels, and antioxidant enzyme activity
      of superoxide dismutase (SOD) and catalase (CAT)] were also measured in
      peripheral blood. RESULTS: Comparison of the distances walked revealed no
      significant differences between the LLLT and placebo LLLT groups (p = 0.779).
      Regarding the Borg scale (p = 0.567), heart rate (p = 0.506) as well as systolic
      and diastolic blood pressure (p = 0.164 and p = 0.140, respectively), no
      differences were observed between LLLT and placebo LLLT groups. Application of
      LLLT was not able to change levels of LDH (p = 0.214), oxidative lipid damage (p
      = 0.733), total thiol levels (p = 0.925), SOD (p = 0.202), and CAT (p = 0.825)
      enzyme activities. CONCLUSIONS: Acute LLLT improved neither functional capacity
      to exercise nor the markers of oxidation after CABG. TRIAL REGISTRATION:
      Registered as a clinical trial (NCT02688426).

PMID- 29466118
TI  - Effectiveness of a Radiographic Anatomy Software Application for Enhancing
      Learning of Veterinary Radiographic Anatomy.
AB  - The goal of this study was to determine the effectiveness of an interactive
      radiology software application that we developed to enhance learning of normal
      canine radiographic anatomy. All first-year veterinary medical students were
      eligible to participate in this subject pre-test-post-test experimental design.
      When presented with the software application, all students had completed two
      terms of gross anatomy in which the complete anatomy of the dog had been taught
      using a combination of lectures and laboratory dissections, including
      radiographic examples. The software application was divided into four body
      regions: front limb, hind limb, skull/spine, and thorax/abdomen, each with a
      learning mode and a quiz mode. Quizzes were composed of 15 questions drawn pseudo
      randomly without repeat from all structures within a region (median 206
      structures). Students were initially given the software application with only the
      quiz mode activated. After completing four quizzes, one for each body region,
      students were given access to the software application with both learning mode
      and quiz mode activated. Students were instructed to spend 30 minutes using the
      learning mode to study the radiographic anatomy of each region and to retake each
      quiz. Quiz scores after using the learning mode were significantly higher for
      each body region (p<.001), with a large effect size for all four regions (Cohen's
      d=0.83-1.56). These results suggest that this radiographic anatomy software
      application is an effective tool for students to use to learn normal radiographic
      anatomy.

PMID- 29466120
TI  - A Modified Technique to Create a Standardized Floppy Nissen Fundoplication
      Without a Bougie.
AB  - INTRODUCTION: Nissen fundoplication is frequently applied in the surgical
      treatment of patients with gastroesophageal reflux disease (GERD). When the
      gastroesophageal junction remains too large or becomes too narrow, persistent
      GERD or dysphagia may occur. To assure a correct size of the gastroesophageal
      junction, the fundoplication can be created over a bougie. However, this
      increases the risk of esophageal perforation. Therefore, we have modified a
      previously described technique to create a standardized fundoplication without
      the use of a bougie. In this article, we describe this technique and demonstrate
      the initial results. MATERIALS AND METHODS: We describe a technique to create a
      standardized Nissen fundoplication. After suture repair of the hiatal hernia,
      three marking sutures were placed on the gastric fundus, based on an equilateral
      triangle. The size of this triangle determines the final diameter of the
      fundoplication. With these measurements, we assure sufficient patency, minimize
      rotation, and create a more reproducible fundoplication that may reduce
      postoperative dysphagia. RESULTS: We have operated 15 patients according to this
      technique. Mean operative time was 69.5 (SD 8.4) minutes, no complications
      occurred. There was no early dysphagia and the mean length of stay was 1.3 days
      (1-2). Quality of life after 1 year was excellent. CONCLUSIONS: This modified
      method for standardized Nissen fundoplication is safe and might reduce
      postoperative dysphagia. Quality of life after 1 year is excellent. The effect on
      postoperative dysphagia and the reproducibility of this technique should be
      established in a large prospective study.

PMID- 29466121
TI  - Can the AFR Approach Stand Up to the Test of Reasonable Pluralism?

PMID- 29466122
TI  - Using Children's Voice to Optimize Pediatric Participation in Medical Decision
      Making.

PMID- 29466123
TI  - Pediatric Participation in a Diverse Society: Accounting for Social Inequalities
      in Medical Decision Making.

PMID- 29466124
TI  - A Framework for Evaluating a Minor's Involvement in Medical Decision Making.

PMID- 29466125
TI  - Distributive Justice and Priority Setting in Health Care.

PMID- 29466126
TI  - More Than "Just Don't Say No": Taking Pediatric Decision Making Seriously.

PMID- 29466127
TI  - A Decision Made Well.

PMID- 29466128
TI  - The Distinct and Complementary Roles of Procedural and Outcome-Based Justice in
      Health Policy.

PMID- 29466129
TI  - Pediatric Participation in Medical Decision Making: The Devil Is in the Details.

PMID- 29466130
TI  - The California Cap-and-Trade Program: A Model Policy for Promoting Environmental
      Justice Using Accountability for Reasonableness.

PMID- 29466132
TI  - Accountability for Reasonableness or Equality of Resources?

PMID- 29466131
TI  - Optimizing Children's Involvement in Decision Making Requires Moving Beyond the
      Concept of Ability.

PMID- 29466134
TI  - Some Remarks on Accontability for Reasonableness.

PMID- 29466133
TI  - Ethical Dilemmas in Protecting Susceptible Subpopulations From Environmental
      Health Risks: Liberty, Utility, Fairness, and Accountability for Reasonableness.
AB  - Various U.S. laws, such as the Clean Air Act and the Food Quality Protection Act,
      require additional protections for susceptible subpopulations who face greater
      environmental health risks. The main ethical rationale for providing these
      protections is to ensure that environmental health risks are distributed fairly.
      In this article, we (1) consider how several influential theories of justice deal
      with issues related to the distribution of environmental health risks; (2) show
      that these theories often fail to provide specific guidance concerning policy
      choices; and (3) argue that an approach to public decision making known as
      accountability for reasonableness can complement theories of justice in
      establishing acceptable environmental health risks for the general population and
      susceptible subpopulations. Since accountability for reasonableness focuses on
      the fairness of the decision-making process, not the outcome, it does not
      guarantee that susceptible subpopulations will receive a maximum level of
      protection, regardless of costs or other morally relevant considerations.

PMID- 29466135
TI  - Saving Environmental Justice From Proceduralism.

PMID- 29466136
TI  - The Default Position: Optimizing Pediatric Participation in Medical Decision
      Making.
AB  - Inclusion of children in medical decision making, to the extent of their ability
      and interest in doing so, should be the default position, ensuring that children
      are routinely given a voice. However, optimizing the involvement of children in
      their health care decisions remains challenging for clinicians. Missing from the
      literature is a stepwise approach to assessing when and how a child should be
      included in medical decision making. We propose a systematic approach for doing
      so, and we apply this approach in a discussion of two challenging clinical cases.
      The approach is informed by a literature review, and is anchored by case studies
      of teenagers' refusal of clinical care, regulatory requirements for research
      assent, and the accepted approach to involving cognitively impaired adults in
      medical decisions.

PMID- 29466137
TI  - Intergenerational and Social Justice: There Is More to Environmental Justice Than
      Accountability for Reasonableness.

PMID- 29466138
TI  - Pediatric Participation in Medical Decision Making: Optimized or Personalized?

PMID- 29466140
TI  - Human Rights Against Polluters: More Than Protecting "Susceptible" Populations.

PMID- 29466139
TI  - Rights, Reasonableness, and Environmental Harms.

PMID- 29466141
TI  - Early Integration of Pediatric Participation in Health Care as Preventive Ethics.

PMID- 29466142
TI  - Review of Jonathan Ives, Michael Dunn, and Alan Cribb, eds., Empirical Bioethics:
      Theoretical and Practical Perspectives1.

PMID- 29466143
TI  - Bringing Values, Relationships, Environments, and Climate Change to Policy
      Deliberations.

PMID- 29466144
TI  - Contextualizing Pediatric Decision Making Within an Ethics of Families.

PMID- 29466145
TI  - The role of ultrasonography in the diagnosis of anterior cruciate ligament
      injury: A systematic review and meta-analysis.
AB  - To evaluate the value of ultrasonography in the diagnosis of anterior cruciate
      ligament injury (ACL injury) by conducting a systematic review and meta-analysis.
      A literature search was carried out in the Cochrane Library, Embase, Pubmed
      databases and included studies prior to April 2017. Based on inclusion and
      exclusion criteria, studies evaluating ultrasound to diagnose ACL injury were
      selected. MRI, arthroscopy and clinical-follow were considered the reference
      standards. The diagnostic accuracy of ultrasound was assessed using a combination
      of sensitivity, specificity, likelihood ratio (LR), post-test probability,
      diagnostic odds ratio (DOR) and by summarizing the area under the receiver
      operating characteristic (SROC) curve. A total of 4 studies involving 246
      patients were eventually included in the analysis. In these four studies, the
      combined sensitivity, specificity, positive likelihood ratio, negative likelihood
      ratio, post-test probability and DOR were 90.0% (95% CI: 77-96), 97% (95% CI: 90
      99), 31.08 (95% CI: 8.75-110.41), 0.11 (95% CI: 0.05-0.24), 89% (3%) and 288.81
      (95% CI: 78.51-1062.48), respectively. The area under the SROC curve was 0.98
      (95% CI: 0.97-0.99). Our meta-analysis showed that ultrasound can play an
      important role in the diagnosis of ACL injury. Because of its high sensitivity,
      high specificity and high diagnostic ability, ultrasound should be a part of the
      standard diagnostic work-up of an ACL injury.

PMID- 29466146
TI  - Pleural Disease.

PMID- 29466147
TI  - A Framework for Ethical Payment to Research Participants.

PMID- 29466148
TI  - Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.

PMID- 29466149
TI  - Case 6-2018: A 35-Year-Old Woman with Headache, Subjective Fever, and Anemia.

PMID- 29466150
TI  - Nonalcoholic Steatohepatitis.

PMID- 29466151
TI  - Controlling the Swing of the Opioid Pendulum.

PMID- 29466152
TI  - Hybrid Strategy to Prevent Venous Thromboembolism after Joint Arthroplasty.

PMID- 29466153
TI  - Prosthesis Type for Aortic- and Mitral-Valve Replacement.

PMID- 29466154
TI  - Developing Anticancer Drugs in Orphan Molecular Entities - A Paradigm under
      Construction.

PMID- 29466155
TI  - Two Pelvic Masses.

PMID- 29466157
TI  - Hematometrocolpos in a Teenager.

PMID- 29466158
TI  - The Psychology of Clinical Decision Making - Implications for Medication Use.

PMID- 29466156
TI  - Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children.
AB  - BACKGROUND: Fusions involving one of three tropomyosin receptor kinases (TRK)
      occur in diverse cancers in children and adults. We evaluated the efficacy and
      safety of larotrectinib, a highly selective TRK inhibitor, in adults and children
      who had tumors with these fusions. METHODS: We enrolled patients with
      consecutively and prospectively identified TRK fusion-positive cancers, detected
      by molecular profiling as routinely performed at each site, into one of three
      protocols: a phase 1 study involving adults, a phase 1-2 study involving
      children, or a phase 2 study involving adolescents and adults. The primary end
      point for the combined analysis was the overall response rate according to
      independent review. Secondary end points included duration of response,
      progression-free survival, and safety. RESULTS: A total of 55 patients, ranging
      in age from 4 months to 76 years, were enrolled and treated. Patients had 17
      unique TRK fusion-positive tumor types. The overall response rate was 75% (95%
      confidence interval [CI], 61 to 85) according to independent review and 80% (95%
      CI, 67 to 90) according to investigator assessment. At 1 year, 71% of the
      responses were ongoing and 55% of the patients remained progression-free. The
      median duration of response and progression-free survival had not been reached.
      At a median follow-up of 9.4 months, 86% of the patients with a response (38 of
      44 patients) were continuing treatment or had undergone surgery that was intended
      to be curative. Adverse events were predominantly of grade 1, and no adverse
      event of grade 3 or 4 that was considered by the investigators to be related to
      larotrectinib occurred in more than 5% of patients. No patient discontinued
      larotrectinib owing to drug-related adverse events. CONCLUSIONS: Larotrectinib
      had marked and durable antitumor activity in patients with TRK fusion-positive
      cancer, regardless of the age of the patient or of the tumor type. (Funded by
      Loxo Oncology and others; ClinicalTrials.gov numbers, NCT02122913 , NCT02637687 ,
      and NCT02576431 .).

PMID- 29466160
TI  - Influenza Season and ARDS after Cardiac Surgery.

PMID- 29466159
TI  - Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty.
AB  - BACKGROUND: Clinical trials and meta-analyses have suggested that aspirin may be
      effective for the prevention of venous thromboembolism (proximal deep-vein
      thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but
      comparisons with direct oral anticoagulants are lacking for prophylaxis beyond
      hospital discharge. METHODS: We performed a multicenter, double-blind,
      randomized, controlled trial involving patients who were undergoing total hip or
      knee arthroplasty. All the patients received once-daily oral rivaroxaban (10 mg)
      until postoperative day 5 and then were randomly assigned to continue rivaroxaban
      or switch to aspirin (81 mg daily) for an additional 9 days after total knee
      arthroplasty or for 30 days after total hip arthroplasty. Patients were followed
      for 90 days for symptomatic venous thromboembolism (the primary effectiveness
      outcome) and bleeding complications, including major or clinically relevant
      nonmajor bleeding (the primary safety outcome). RESULTS: A total of 3424 patients
      (1804 undergoing total hip arthroplasty and 1620 undergoing total knee
      arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11
      of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%)
      in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence
      interval [CI], -0.55 to 0.66; P<0.001 for noninferiority and P=0.84 for
      superiority). Major bleeding complications occurred in 8 patients (0.47%) in the
      aspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18
      percentage points; 95% CI, -0.65 to 0.29; P=0.42). Clinically important bleeding
      occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the
      rivaroxaban group (difference, 0.30 percentage points; 95% CI, -1.07 to 0.47;
      P=0.43). CONCLUSIONS: Among patients who received 5 days of rivaroxaban
      prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with
      aspirin was not significantly different from rivaroxaban in the prevention of
      symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health
      Research; ClinicalTrials.gov number, NCT01720108 .).

PMID- 29466161
TI  - Placing a Lumbar Epidural Catheter.

PMID- 29466162
TI  - Preventive Therapies for Chronic Migraine.

PMID- 29466163
TI  - Our Other Prescription Drug Problem.

PMID- 29466165
TI  - Tofacitinib for Psoriatic Arthritis.

PMID- 29466166
TI  - [Optimization of Invasive Treatment Strategy in Patients With Non-ST Elevation
      Acute Coronary Syndrome].
AB  - OBJECTIVE: to compare strategies of invasive treatment of patients with non-ST
      elevation acute coronary syndrome (NSTEACS) hospitalized in 2014 and 2015.
      MATERIALS AND METHODS: We have analyzed treatment strategy used in patients with
      NSTEACS hospitalized in cardio-reanimation department of a city hospital during
      one month in two successive years (January 2014 and November 2015). We have
      compared indications to, and timing of coronary angiography, numbers of performed
      percutaneous coronary interventions (PCI) and coronary artery bypass grafting
      surgeries. RESULTS: Portion of patients subjected to invasive procedures in 2014
      was 26 %, in 2015-42 %. All 32 primary procedures were PCIs. An increase was due
      to delayed interventions (24-72 hours), which were not performed in 2014. We also
      more often used selective multivessel coronary stenting, what facilitated
      availability of invasive treatment for elderly patients. Hospital mortality of
      patients with NSTEACS decreased from 16 to 7 %.

PMID- 29466164
TI  - Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.
AB  - BACKGROUND: A strategy of administering a neonatal rotavirus vaccine at birth to
      target early prevention of rotavirus gastroenteritis may address some of the
      barriers to global implementation of a rotavirus vaccine. METHODS: We conducted a
      randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the
      efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing
      rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB,
      administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks
      of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or
      placebo. The primary analysis was conducted in the per-protocol population, which
      included only participants who received all four doses of vaccine or placebo
      within the visit windows, with secondary analyses performed in the intention-to
      treat population, which included all participants who underwent randomization.
      RESULTS: Among the 1513 participants in the per-protocol population, severe
      rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the
      participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal
      schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine
      group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence
      interval [CI], 44 to 91) in the neonatal-schedule group (P<0.001), 51% (95% CI, 7
      to 76) in the infant-schedule group (P=0.03), and 63% (95% CI, 34 to 80) in the
      neonatal-schedule and infant-schedule groups combined (combined vaccine group)
      (P<0.001). Similar results were observed in the intention-to-treat analysis (1649
      participants); the vaccine efficacy was 68% (95% CI, 35 to 86) in the neonatal
      schedule group (P=0.001), 52% (95% CI, 11 to 76) in the infant-schedule group
      (P=0.02), and 60% (95% CI, 31 to 76) in the combined vaccine group (P<0.001).
      Vaccine response, as evidenced by serum immune response or shedding of RV3-BB in
      the stool, occurred in 78 of 83 participants (94%) in the neonatal-schedule group
      and in 83 of 84 participants (99%) in the infant-schedule group. The incidence of
      adverse events was similar across the groups. No episodes of intussusception
      occurred within the 21-day risk period after administration of any dose of
      vaccine or placebo, and one episode of intussusception occurred 114 days after
      the third dose of vaccine in the infant-schedule group. CONCLUSIONS: RV3-BB was
      efficacious in preventing severe rotavirus gastroenteritis when administered
      according to a neonatal or an infant schedule in Indonesia. (Funded by the Bill
      and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials
      Registry number, ACTRN12612001282875 .).

PMID- 29466167
TI  - [Lung Hyperinflation in Chronic Obstructive Pulmonary Disease and Long-Term
      Outcomes of Percutaneous Coronary Intervention].
AB  - OBJECTIVE: to assess the effect of lung hyperinflation (LHI) in patients with
      chronic obstructive pulmonary disease (COPD) on longterm outcomes of percutaneous
      coronary intervention (PCI). MATERIALS AND METHODS: Patients with COPD who
      suffered stable ischemic heart disease and underwent PCI (n=135) were included in
      a prospective cohort study. LHI was found in 60 patients, while 75 patients had
      no LHI. Evaluation included comparing the frequency of major adverse cardiac
      events (MACE) (cardiac death, myocardial infarcpunktion [MI], stroke, repeat
      revascularization) and Kaplan-Mayer curves between groups of patients with and
      without LHI. Associations of parameters of pulmonary function and plasma levels
      of high sensitivity C-reactive protein (hsCRP) with occurrence of MACE were also
      elucidated. Duration of follow-up was up to 3 years (median 20 months). RESULTS:
      Study groups did not differ significantly by main factors of cardiovascular risk,
      except plasma level of hsCRP. MACE occurred in 41.7 and 26.7 % of patients in
      groups with and without LHI, respectively (p=0.097). However, divergence of the
      Kaplan-Meier curves was statistically significant (p=0.04). The main contribution
      was made by cardiac death, MI and stroke (21.7 and 8.0 % among patients with and
      without LHI; p=0.027). No difference was found regarding repeat
      revascularization. The correlation between functional residual lung capacity and
      plasma level of hsCRP was closer than the correlation between forced expiratory
      volume in 1 second and hsCRP level (r=0.36 and r=0.19; p.

PMID- 29466168
TI  - [Lung Ventilation Efficiency and Quality of Life After Orthotopic Heart
      Transplantation].
AB  - : Aim of the study was assessment of efficiency of lung ventilation and its
      relationship with quality of life in patients undergoing orthotopic heart
      transplantation (OHT). MATERIALS AND METHODS: The study involved 40 patients with
      terminal chronic heart failure (CHF) included in the waiting list for heart
      transplantation. Before surgery and after OHT all patients underwent
      cardiopulmonary exercise testing, evaluation of clinical status and quality of
      life (QL) according to the 36-Item Short Form Survey (SF-36). RESULTS: During the
      follow-up period (5 years) after OHT there were a significant increase in
      physical capacity, two-fold increase of peak oxygen consumption (VO2),
      normalization of VE/VCO2 slope level, improvement of the efficiency of the VO2
      recovery within first minute and reduction of the VO2 recovery time. OHT was
      associated with significant improvement of physical and mental health components
      of QL. Among exercise test parameters significantly associated with improved
      physical health component of QL were increments in exercise capacity, peak VO2,
      rate of VO2 recovery within first minute. There was no relationship between
      cardiopulmonary parameters of exercise test and mental health component of QL.
      CONCLUSION: In patients with terminal CHF OHR led to significant increase of the
      lung ventilation efficiency and QL. Factors contributing to QL improvement after
      OHT were augmentation of left ventricular ejection fraction and reduction of CHF
      NYHA class. Among cardiopulmonary exercise test parameters, a high predictive
      value relative to improvement of subjective assessment of physical health
      component of QL showed exercise capacity, peak VO2, and efficiency of VO2
      recovery within first minute.

PMID- 29466169
TI  - [Selection of Optimal Therapy at Correction of the Anemic Syndrome in Patients
      With Chronic Heart Failure].
AB  - PURPOSE: to study efficacy of various schemes of therapy of patients with chronic
      heart failure (CHF) and anemia. MATERIALS AND METHODS: We included in this study
      208 patients with CHF of ishemic etiology (mean age 60.6+/-1.4 years, 174 with
      and 34 without anemia). According to therapeutic regimen of the use of methoxy
      polyethylene glycol-epoetin beta (MEB, 0.60 msg/kg) and intravenous (IV) iron
      hydroxide sucrose complex all patients were divided into 4 groups. In all
      patients before and after treatment we determined Hb, Ht, plasma levels of
      ferritin, erythropoietin (EPO), NT-proBNP, IL-1, IL-6, TNF-alpha, transferrin
      saturation (TS), total vascular peripheral resistance, and parameters of systolic
      and diastolic function of left ventricular (LV) myocardium (by echocardiography
      and doppler echocardiography). RESULTS: In patients with NYHA class I-IV CHF and
      anemia increases of Hb, Ht, TS, levels of EPO and ferritin occurred during
      treatment by basic drugs combained with MEB. In subgroups of patients with NYHA
      class I-II and III-IV the 6-minute walk distance significantly increased by 25.1
      and 38.3%, and GFR- by 24.5 and 14.9%, respectively. At the background of therapy
      with IV iron we observed significant increases of Hb, plasma level of ferritin,
      and TS. Combined treatment with MEB and IV iron was associated with positive
      dynamics of Hb, Ht, levels of ferritin, EPO, NT-proBNP, and IL-6. In this group
      in subgroups of patients with NYHA class I-II and III-IV the 6-minute walk
      distance significantly increased by 21.6 (p.

PMID- 29466170
TI  - [Phenomenological Regularities of Assessment of Left Ventricle Function in Mitral
      Valve Insufficiency].
AB  - OBJECTIVE: to examine relationship between anatomical changes of the left
      ventricle (LV), dynamics of velocity of its volume modification, and blood flows
      in the LV in patients with mitral regurgitation (MR) before and after surgical
      treatment. MATERIALS AND METHODS: We included into this study 58 patients with
      severe 3-4 degree MR (38 men, 20 women aged 24-69 [mean age 51+/-9] years) in
      sinus rhythm (96 %) or atrial fibrillation (4 %). The control group included 86
      healthy volunteers, mean age 39+/-7 years. Transthoracic echocardiographic
      studies were performed in both groups by standard technique at rest using a high
      quality echocardiograph Vivid E9, equipped with a 3.5-4.6 MHz multi frequency
      transducer (in patients before and after surgical repair - mitral valve [MV]
      replacement and MV reconstruction with annuloplasty ring). The analysis of files
      recorded was performed off-line by vector analysis technique including estimation
      of myocardial deformation velocities and dynamics of LV volume modification,
      construction of "flow-volume" diagram, calculation of the expended kinetic
      energy, and registration of intraventricular blood flows. RESULTS: End diastolic
      volume (EDV), end systolic volume (ESV) and total stroke volume (TSV) (effective
      + retrograde) were significantly increased in patients with severe LV volume
      overload before surgery in comparison with the control group (p.

PMID- 29466171
TI  - [Duration of Dual Antiplatelet Therapy in Patients With Ischemic Heart Disease
      After Implantation of Endovascular Stents].
AB  - Optimal duration of dual antiplatelet therapy (DAPT) after stent implantation is
      uncertain. Some patients have an extended risk of thrombotic complications
      including that of very late stent thrombosis after cessation of recommended
      course of DAPT (6-12 months). On the other hand, there is a real risk of bleeding
      on DAPT. In this review, we present and discuss results of clinical trials of
      long-term DAPT and data of their meta-analyses. The review also contains
      consideration of some aspects of new AHA/ACC recommendations (2016) on duration
      of DAPT.

PMID- 29466172
TI  - [Effects of Glucose Lowering Drugs on Cardiovascular Risk in Type 2 Diabetes
      Mellitus: Realities and Perspectives].

PMID- 29466173
TI  - [MicroRNAs as Biomarkers of Cardiovascular Diseases].
AB  - The fact that microRNAs play an important role in the development and
      pathogenesis of cardiovascular disease is beyond doubt. This article provides a
      brief overview of recent data that relate to microRNA expression in various
      cardiovascular diseases. Detecting significant changes in the level of expression
      of these molecules in various diseases means that microRNAs can be considered to
      be potential biomarkers of human pathologies including heart failure. Studying
      the relationship between the mechanisms of cardiovascular disease and the level
      of expression of a variety of microRNAs, as well as establishing their exact
      relationships with the genes is an urgent problem and requires further research.

PMID- 29466174
TI  - [Pharmacological Properties of Loop Diuretics and Their Clinical Effects].
AB  - Edematous states caused by an excessesive extracellular fluid retention are major
      components of cardiovascular and renal disorders including chronic kidney
      disease, nephrotic syndrome, and heart failure. The use of diuretic drugs from
      various groups including loop duiretics are important means of pharmacological
      correction of these clinical conditions. Moreover, diuretics used to lower bood
      pressure as a part of antihypertensive treatment, reduce cardiovascular events.
      The response of patients to the dose of a diuretic is reflected by a sigmoid dose
      response curve which can be affected by changes of sodium content in the body.
      Loop diuretics may fail to control salt and water retention despite the use of
      appropriate doses. The main reasons for loop diuretic resistance may be
      determined by further reduction of glomerular filtration rate and reduced peak
      concentration of loop diuretics in primary urine. Chronic treatment with loop
      diuretics can cause compensatory hyperthrophy of epithelial cells along the
      ascending limb of the loop of Henle and thus decrease of its diuretic effect. The
      principles of avoiding this phenomenon are the restriction of sodium intake,
      correction of doses, timing and frequency of drug administration, and use of
      combination diuretic therapy. Loop diuretic - related adverse events that involve
      uricaemia and ototoxicity also should be taken into consideration.

PMID- 29466175
TI  - [Giant Aneurysms in Coronary Arteries of a Young Woman].
AB  - Coronary arteries aneurysms with their thrombotic occlusion are known to be
      detected in young patients who have suffered Kawasaki disease in childhood. The
      other vascular beds are usually not involved. In the literature one can find not
      enough information regarding diagnostics of this pathology, as well as no
      specific treatment algorithm. We present here a clinical case of re-emergence of
      giant aneurysms of coronary arteries in the young female patient with subsequent
      immuno-histological confirmation of previous Kawasaki disease.

PMID- 29466176
TI  - [Significance of Electrocardiography in Patients With Arterial Hypertension].
AB  - The article is devoted to the analysis of significance of electrocardiography for
      assessment of anatomical-functional measurements of the heart in patients with
      arterial hypertension. Modern methods of calculation of the left ventricular
      myocardial mass are presented with corresponding recommended normal ranges
      values. The article contains discussion of variants of left ventricular
      remodeling, significance of functional indexes characterizing the state of
      systolic and diastolic function of the heart, parameters of deformation of the
      left ventricle for diagnosis of causes of left ventricular hypertrophy, as well
      as for assessment of prognosis.

PMID- 29466177
TI  - [Anticoagulant therapy and prognosis in patients with CHF and AF in the setting
      of real-life clinical practice].
AB  - BACKGROUND: Prevalence of atrial fibrillation (AF) grows with the increase in CHF
      FC and reaches 45% in III-IV FC CHF. With an adequate anticoagulant (AC) therapy,
      the risk of thromboembolic complications does not significantly differ between
      patients with I-II FC and III-IV FC CHF. Of particular interest is studying
      administration of the anticoagulant treatment and correspondence between the SAMe
      TT2R2 scale and actual TTR values in patients with CHF and AF in real-life
      clinical practice. AIM: Toanalyze the efficacy of anticoagulant therapy and
      prognosis in patients with CHF and AF in the setting of real-life clinical
      practice. MATERIALS AND METHODS: The study included 272 patients with CHF and AF
      who were discharged from the hospital where they had been treated for
      decompensated CHF and who were followed up as outpatients for a year. Efficacy of
      the AC therapy was evaluated; parameters of CHA2DS2-VASc, HAS-BLED, and SAMe
      TT2R2 scales were calculated at baseline. TTR was computed to determine the
      maintenance time. RESULTS: Patients with CHF had permanent (56.3%), persistent
      (38.6%), or paroxysmal (5.1%) AF. The mean CHA2DS2-VASc score was 3.83+/-1.16 and
      the mean HAS-BLED score was 1.3+/-0.83. SAMe-TT2R2 scores were 0 for 1.6% of
      patients; 1 for 36.9%, and 2< for 61.5%. At baseline, one third of patients with
      CHF and AF received antiplatelet therapy (APT) and every forth patient received
      no therapy. At one year, 69.0% of patients took AC on a constant basis (r.

PMID- 29466178
TI  - [The use of platform for remote monitoring on the base of mobile app for
      improving self-care in patients with chronic heart failure].
AB  - AIM: To determine a possibility for improving the capability of patients with
      chronic heart failure (CHF) for self-care and self-control using a remote
      monitoring platform on a basis of mobile application. MATERIALS AND METHODS: The
      study included 142 patients with CHF of different etiology. During the stay in
      hospital, patients attended structured classes on different aspects of self
      control and self-care in CHF. The group of active management consisted of 47
      patients who subsequently used a version of mobile application. The control group
      consisted of 95 patients with CHF. The remote monitoring platform was based on a
      translated to Russian version of the European Heart Failure Self-Care Behavior
      Scale (EHFScBS_9), which included 9 items addressing different issues of
      selfcontrol. Responses were presented as a scale ranging from "completely agree"
      (1) to "completely disagree (5). The total score was calculated by adding scores
      for each item. The lower the score the better was the capability of CHF patients
      for self-care. The followup duration was 6 months. RESULTS: On admission, the
      mean EHFScBS_9 score decreased to 15+/-2.3 in the mobile application group
      whereas in the control group, the mean score was 23.95+/-3.02, which indicated a
      significantly better capability for self-care in the mobile application group (p.

PMID- 29466179
TI  - [Characteristics and treatment of hospitalized patients with CHF].
AB  - The article analyzes some characteristics of hospitalized patients with
      decompensated chronic heart failure (HF) according to data from Russian and
      international registries, management of decompensated HF, and tactics for
      titration of evidence-based disease-modified therapies. The demographic
      characteristics of the patients from the registers that were used for the
      research are similar. Yet, the proportion of HF patients with preserved LVEF was
      greater according to data from several Russian studies. Meanwhile, with the
      patients that did not receive any loop diuretics and therefore had apparently no
      congestion signs being excluded from the analysis, the proportion of HF patients
      with preserved LVEF became similar to that from the international studies. The
      registers also showed that pulmonary edema and acute left ventricular failure
      were observed in less than a half of the cases. Nevertheless, patients with mild
      congestion symptoms still have bad lingering prognosis and require the same
      amount of medical attention. Up to 40 % of admissions for decompensated CHF
      resulted from a dietary disorder (excessive sodium consumption), low compliance
      with therapy and lack of access to primary care providers. Furthermore, the
      analysis of the outpatient treatment administered prior to the forthcoming
      hospitalization showed a low prescription rate of evidence-based disease
      modifying therapies (ACEi or ARNi, BB, MRA). It is emphasized that in part of
      patients the administration and/or titration of this therapy can be started
      during hospitalization. The article also discusses the use of a new class of
      drugs, angiotensin receptor-neprilysin inhibitors (ARNi), including not only
      transferring patients from ACEi to ARNi but also the possibility of administering
      ARNi to stable, hospitalized patients who do not require intravenous diuretics
      and inotropic drugs.

PMID- 29466180
TI  - [Possibilities of modern echocardiographic technologies in the early diagnosis of
      the cardiotoxic effect of chemotherapy drugs anthracycline series in cancer
      patients].
AB  - Chronic heart failure following chemotherapy for cancer is a relevant issue of an
      adverse cardiovascular prognosis and premature death in cancer patients. This
      category of patients requires thorough and chronic monitoring of the
      cardiovascular system, prevention and treatment of cardiovascular complications
      of chemotherapy, such as IHD, systolic or diastolic myocardial dysfunction,
      arterial or pulmonary hypertension, pulmonary thromboembolism, pericarditis,
      stroke, and peripheral vascular disease. However, many aspects of this important
      interdisciplinary issue presently remain understudied. For instance, it is still
      impossible to predict long-term consequences of chemotherapy for cancer and
      development of the associated cardiovascular complications listed above. Baseline
      evaluation of the risk for cardiovascular complications is a major component in
      management of such patients. High-risk patients need an individual, detailed
      schedule of cardiovascular treatment throughout and after the course of
      chemotherapy. Furthermore, early detection of subclinical myocardial dysfunction
      is critical for prevention of the most threatening cardiovascular complications
      of chemotherapy, CHF. Detecting impaired LV EF following chemotherapy is,
      unfortunately, only a late predictor of irreversible changes, such as toxic
      cardiomyopathy and clinically pronounced, rapidly progressing CHF. Markers of
      myocardial injury, high-sensitivity troponins and natriuretic peptides, in
      combination with up-to-date EchoCG technologies have been recently used. Their
      use, for instance, for evaluation of LV myocardial global longitudinal strain to
      detect early, reversible changes in structure and mechanics of the myocardium is
      promising for ultimate improvement of prediction for such patients.

PMID- 29466181
TI  - [Prognostic value of glycemic variability in patients with decompensated chronic
      heart failure and diabetes mellitus].
AB  - The review focused on the prognostic significance of hyperglycemia and glycemia
      variability in patients both with type 2 DM and without previously detected
      disorders of carbohydrate metabolism hospitalized for decompensated CHF. Results
      of recent studies of glycemia variability, stress-induced hypoglycemia, and their
      effect on prognosis for patients with decompensated CHF were analyzed.

PMID- 29466182
TI  - [Hallmarks of preventive counseling in coronary heart disease patients with
      abdominal obesity].
AB  - Patients with coronary heart disease (CHD) and abdominal obesity (AO) are a
      priority group for the most active implementation of secondary prevention
      efforts. The paper focuses on most challenging issues of cardiovascular risk
      factors (RFs) correction via comprehensive cardiac rehabilitation (CR) programs
      in patients with CHD and AO. Based on large randomized clinical trials results,
      intensive behavioral interventions in the form of counselling are beneficial for
      such patients especially during the long-term support stage. They produce small
      but important changes in health behaviors (which translate into weight reduction,
      more healthy nutrition and higher physical activity) and improve selected
      intermediate clinical endpoints.

PMID- 29466183
TI  - [Pulmonary arterial hypertension and chronic heart failure as dasatinib
      cardiotoxicity. A case report].
AB  - Modern treatment of patients with oncohematological diseases has allowed to
      achieve remission or even convalescence in many cases. One of ambitious aims put
      forward by the hematological society is 100% survival and preservation of quality
      of life in patients with chronic myeloid leukemia (CML). This hope is related
      with the emergence of targeted therapy for CML. The second-generation tyrosine
      kinase inhibitor, dasatinib, which is used for treatment of CML, can occasionally
      induce severe pulmonary hypertension (PH). We presented here a case report of
      such cardiotoxicity, which was evident as PH and heart failure in a young female
      patient with CML treated with dasatinib. Information from published reports about
      this type of cardiotoxicity is provided. At present time, dasatinib is beginning
      to be extensively used also in other oncological diseases. For this reason,
      cardiologists and physicians should be aware of this cardiotoxicity, which can
      cause heart failure in dasatinib-treated patients.

PMID- 29466184
TI  - [Efficiency of primary prevention for diseases caused by atherosclerosis in
      patients at high cardiovascular risk in Russia and other European countries (Part
      2)].
AB  - BACKGROUND: The picture of primary prevention obtained from real-life practice
      makes possible scheduling measures for prevention improvement. AIM: To analyze
      features of drug and non-drug therapy aimed at decreasing cardiovascular risk in
      Russian patients with a high risk (HR) of CVD compared with the study general
      population. MATERIALS AND METHODS: 14 European countries, including the Russian
      Federation, participated in this cross-sectional study. The study included
      patients aged 18-80 without clinical signs of atherosclerosis who have received
      antihypertensive and/or lipid-lowering therapy and/or therapy for diabetes
      mellitus (DM) within >6 to.

PMID- 29466185
TI  - [Factors affecting effective patient management for preventing recurrent coronary
      events].
AB  - AIM: To identify factors affecting effective management of patients with
      myocardial infarction for preventing recurrent coronary events in the outpatient
      setting. MATERIALS AND METHODS: The study group consisted of patients (n=111)
      with recurrent myocardial infarction. The control group consisted of patients
      with primary myocardial infarction (n=89) after percutaneous coronary
      intervention. Social and demographic, clinical and behavioral factors (weight
      loss, smoking cessation, adherence to therapy, physical and psychological
      rehabilitation) were evaluated. RESULTS: Risk factors contributing to the
      development of repeated MI were as follows: patients' age, concomitant
      polyvascular and multivessel disease, arterial hypertension,
      hypercholesterolemia, excess weight and smoking, poor adherence to the
      recommendations of cardiologists and general physicians. CONCLUSION: The analysis
      of the effectiveness of the management of patients with myocardial infarction
      demonstrated the importance of the outpatient rehabilitation in preventing
      repeated acute coronary events.

PMID- 29466186
TI  - [Safety and efficacy of long-term treatment with different ASA forms in patients
      with stable IHD and a high risk for development of gastropathy by data from a
      cross-sectionals study].
AB  - AIM: To study indexes of efficacy, safety and compliance for different ASA forms
      (Aspirin-Cardio, Cardiomagnyl, Thrombo ASS) used in stable IHD. MATERIALS AND
      METHODS: An open, cross-sectional study compared three groups of patients
      consisting of 200 patients each who had stable IHD and a high risk of
      gastrointestinal disorders and who received a long-term antiaggregant monotherapy
      with one of ASA drugs (group 1, Aspirin Cardio; group 2, Thrombo ASS; group 3,
      Cardiomagnyl). Efficacy, safety and compliance with the treatment were evaluated
      using standard tests and analogue scales; dyspepsia symptoms were evaluated using
      a special, additionally developed questionnaire. RESULTS: The Aspirin-Cardio
      treatment reduced the mean score of GI symptom severity from the questionnaire
      (1.4-1.6 times, r=0.001), requirement for proton pump inhibitors (r=0.002) and
      endoscopy during the ASA treatment the mean score of GI symptom questionnaire >3
      predicted non-compliance or insufficient compliance with a diagnostic sensitivity
      of 58.9 % and specificity of 56.3 % (r=0.002), which makes this value a threshold
      for considering a modification of the treatment. CONCLUSION: Aspirin-Cardio is
      characterized by better safety in respect of GI symptoms and better compliance
      with the treatment during long-term prophylactic therapy. The proposed
      questionnaire for evaluation of GI symptoms can be used for specifying
      indications and modifying the treatment tactics.

PMID- 29466187
TI  - [The clinical significance of copeptin and matrix metalloproteinases in men with
      acute coronary syndrome].
AB  - AIM: To evaluate clinical value copeptin and matrix metalloproteinases in men
      with acute coronary syndrome (ACS). MATERIALS AND METHODS: The study included 152
      men with ACS. After evaluation of the traditional markers of myocardial damage,
      the patients were divided into 2 groups: the first group included patients with
      myocardial infarction (MI) - 84 people, the average age was 56.6+/-1.0 years, the
      second - with unstable angina (UA) - 68 at the age of 61,4+/-1.2 years. All
      patients at admission and after 6 hours and on day 6 of hospitalization were
      evaluated for the level of CPK MB, troponin I, copeptin, MMP-1, MMP-2, MMP-7, MMP
      9 and TIMP-1. RESULTS: Concentration of copeptin at admission in patients with it
      is 3.5 times higher than in the group with UA and significantly higher than that
      of control group. To 6-th day of hospitalization, the concentration of copeptin
      reduced, but nonetheless remains significantly higher than in the control group
      (0,9+/-0,1 vs. 0.2+/-0,0, p=0.000) without significant differences with group UA.
      The level of MMP-1 and MMP-2 in patients with MI and UA at admission higher than
      in the control group, and in case of MI these levels are significantly higher
      than in case of UA. CONCLUSION: The obtained data indicates the possibility of
      using copeptin as a marker of myocardial damage. Additionally, it indicates
      myocardial damage an increase in the level of MMP-1, MMP-2 and MMP-7.

PMID- 29466188
TI  - [Incidence of sinus node dysfunction in patients with long-standing, persistent
      atrial fibrillation who require simultaneous surgical correction of mitral and
      tricuspid valve defects and the "Maze IIIB" procedure].
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common disorder of heart rhythm.
      A series of "Maze" surgery was developed, among which the "Maze III" modification
      is presently a gold standard for surgical treatment of AF. AIM: To study the
      sinoatrial node (SAN) function before and after the "Maze III" surgery. MATERIALS
      AND METHODS: The study included 100 patients (48 males) with persistent and long
      standing persistent AF and valve abnormality. Mean age of patients was 59 years
      and mean AF duration - 4 years. Tachysystolic AF prevailed (62 %); normosystolic
      AF was observed in 31 % of patients; and bradysystolic - in 7 % of patients.
      Electric cardioversion was performed for all patients according to the standard
      method. After successful recovery of the sinus rhythm, the endocardial
      electrophysiological study (EPS) of the heart was performed. Correction of valve
      pathology and the "Maze IIIB" surgery were performed on days 1-2 following EPS.
      The SAN function was evaluated by the time of function recovery (SAN TFR).
      RESULTS: Using electric cardioversion, the sinus rhythm was restored in all
      patients. EPS showed abnormal prolongation of the corrected time for the SAN
      function recovery (CTSANFR) and sinoatrial conduction time (SACT) in 11 % of
      patients. In 2 % of patients, the abnormal prolongation of SACT was an isolated
      conduction disorder. In total, 13 % of patients had SAN dysfunction (SAND). These
      patients received implantable electric cardioverters after a surgical
      intervention (correction of valve abnormality and "Maze III"). The sinus rhythm
      recovered immediately after the surgery. On day 7, steady sinus rhythm was
      observed in 46 % of patients. During the postperfusion period and on the first
      day postsurgery, 62 % of patients had replacement atrioventricular nodal rhythm.
      By the time of discharge from the hospital, the nodal rhythm was observed in 25 %
      of patients. Starting from day 2, the replacement atrial rhythm developed in 13 %
      of patients, and by the time of discharge from the hospital, 24 % of patients had
      a stable atrial rhythm. CONCLUSION: Effectiveness of the surgical treatment for
      persistent and long-standing persistent AF (modified "Maze IIIB" surgery with
      simultaneous correction of the mitral valve (MV) and the tricuspid valve (TV)) in
      the early postsurgery period was 95 %. According to data of preoperative
      endocardial EPS, SAND was observed in 13 % of patients. Following the surgical
      correction of MV and TV defects and the criomodification of the "Maze IIIB"
      surgery, signs of SAND requiring implantation of an electric cardioverter were
      observed in a total of 24 % of patients.

PMID- 29466189
TI  - [Interventional treatment in patients with myocarditis: Pro and Contra].
AB  - AIM: Ventricular tachyarrhythmias (VTs) are often encountered in patients with
      inflammatory heart diseases. VT can become lifethreatening in patients with
      myocarditis, and the management may vary in different types of myocarditis.
      Purpose of the study is to describe VT characteristics in patients with verified
      myocarditis, and to evaluate the efficacy and safety of VT management, when
      tailored to the type of myocarditis. MATERIALS AND METHODS: Study population
      comprised: 56 patients with morphologically verified myocarditis; 18 patients
      with primary cardiomyopathy (control group). All patients underwent full clinical
      evaluation, endomyocardial biopsy (including immunohistochemical analysis). Forty
      (54 %) patients underwent radiofrequency catheter ablation of VT. An implantable
      cardioverter-defibrillator (ICD) was inserted in 17 patients. RESULTS: There was
      no statistically significant difference between myocarditis and primary
      cardiomyopathy groups by demographic and echocardiographic data. In myocarditis
      group, nonsustained VT and/or frequent premature ventricular beats were seen in
      59 % of patients; sustained VT in 12,5 % subjects, 1 patient had a history of
      ventricular fibrillation. VT ablation was associated with a significant decrease
      in VT recurrence (p=0,0009) during the follow-up period. Active myocarditis was
      associated with a higher VT recurrence rate (67 % in active vs. 19 % in
      borderline myocarditis). Among patients with ICD implantation, only one subject
      (with active myocarditis at admission) had life-threatening ventricular
      arrhythmia. CONCLUSION: In this selected group of patients with verified
      myocarditis and clinically significant VTs, catheter ablation seems at least
      partly effective. Patients with borderline myocarditis and symptomatic VTs may
      benefit from ablation. Therefore, morphological diagnostic of myocarditis can be
      a key point in choice of treatment.

PMID- 29466190
TI  - [Disorders of heart structure and function parameters and hepatolienal blood flow
      remodeling in patients with virus-induced cirrhosis].
AB  - AIM: To study heart structure and function parameters and hepatolienal blood flow
      in patients with virus-induced cirrhosis (VIC). MATERIALS AND METHODS: 95
      patients with VIC (mean age, 38.6; disease duration, 4.5 years) were evaluated.
      Doppler EchoCG and Doppler ultrasonic examination of hepatolienal vasculature
      (VIVID E 95 apparatus) were performed. The control group consisted of 19 healthy
      individuals. Statistical analysis was performed using the Statistica 6.0
      software. RESULTS: The study of hepatolienal blood flow showed that the
      splanchnic artery blood flow velocity was increased by 25%, the hepatic vein
      blood flow velocity was increased by 13%, and splanchnic arteries and veins were
      dilated. 24% of VIC patients had moderate pulmonary hypertension associated with
      a 20% dilatation of inferior vena cava (p=0.007), a 28% increase in hepatic vein
      blood flow velocity (p=0.0003), and a 13% decrease in portal vein diameter
      (p=0.001). Four types of left ventricular (LV) geometry were identified: 40% of
      VIC patients had normal geometry; 17% of patients had concentric hypertrophy; 23%
      of patients had concentric remodeling; and 19% had eccentric hypertrophy.
      Features of hepatolienal blood flow were related with the LV geometry type. LV
      diastolic filling was impaired in 44.3% and RV diastolic filling - in 33% of
      patients. In patients with VIC, the disturbed diastolic function was associated
      with 25% reduced hepatic vein blood flow velocity (p=0.05) whereas development of
      RV diastolic dysfunction was associated with 6% reduced portal vein diameter
      (p=0.04), 17% dilated portal vein (p=0.006), and 25% decreased portal vein blood
      flow velocity (p=0.001). Anti-viral therapy resulted in improvement of some
      hepatolienal blood flow parameters. Parameters of splanchnic circulation were
      correlated with cardiodynamic parameters with correlation coefficients from 0.51
      to 0.95 at p.

PMID- 29466191
TI  - [Effectiveness of a long-term education program in patients with prosthetic heart
      valves].
AB  - AIM: The current study was aimed at assessing the effectiveness and the impact of
      a long-term education program, in both inpatient and outpatient treatment
      settings, on adherence to treatment and the quality of life 5 years after heart
      valve replacement. MATERIALS AND METHODS: All the patients were randomly included
      into two study groups. The study group patients (n=176) underwent the long-term
      education program in both inpatient and outpatient treatment settings. The
      control group (n=108) consisted of patients who underwent only an inpatient
      education program. Adherence to treatment and the quality of life were assessed
      before education, at the end of the inpatient and outpatient education and 5
      years after heart valve replacement. Patients' treatment adherence was estimated
      with the Davydov's questionnaire, and the quality of life - with the 36-Item
      Short Form Health Survey. RESULTS: After the completion of the education program,
      the integral index reflecting patients' adherence to treatment in the study group
      remained at the same level, but was 1.4-fold higher compared to the control group
      in the 5-year follow-up. The long-term education program is associated with
      improved quality of life, mainly due to emotional well-being. The study reported
      a correlation between physical functioning and emotional well-being and the
      integral index reflecting patients' adherence to treatment during the follow-up
      period. CONCLUSION: The long-term education program in both inpatient and
      outpatient treatment settings contributed to improved patients' adherence to
      treatment and the quality of life, mainly due to physical functioning. The
      inpatient education program was associated with poor patients' adherence to
      treatment and the quality of life 5 years after heart valve replacement.

PMID- 29466192
TI  - [Factors associated with levels of interleukins -18, -8, and -6 in hypertensive
      patients at high and very high cardiovascular risk].
AB  - AIM: To identify the most significant factor influencing blood levels of
      cytokines in patients at high and very high cardiovascular risk. MATERIALS AND
      METHODS: A patient base from the "Management of chronic patients with multiple
      diseases" project was analyzed. 523 patients (mean age, 87+/-17.8) were included.
      Plasma samples were analyzed for concentrations of sodium, creatinine, IL-1, IL
      2, IL-4, IL-6, IL-8, IL-10, IL-18, and NT-proBNP. GFR was calculated using the
      CKD-EPI formula. Time-related CHF progression was assessed in one year; the time
      related progression was considered an increase in CHF stage. Salt consumption was
      determined using the Charlton: SaltScreener questionnaire at the baseline visit
      and at one year. Low-salt diet containing 5 g of salt per day was recommended to
      all patients; 3.5 g of salt per day was recommended to patients with a documented
      diagnosis of CHF. Statistical analysis was performed using the Statistica 10.0
      software. RESULTS: 52.2 % of included patients consumed 6-10 g of salt per day;
      43.4 % of patients consumed 10 g of salt or more per day; and only 4.4 % of
      patients consumed 5 g of salt or less per day. 21 % of included patients were at
      high risk of cardiovascular complications whereas for the vast majority of
      patients (79 %), the risk was stratified as very high. Two clusters of patients
      were formed based on the grade of hypertension, one-year CHF progression, and
      plasma levels of IL-6, -8, and -18. The one-year progression of CHF most
      significantly influenced the levels of IL-18, -8, and -6. The IL-6 level was
      correlated with the NT-proBNP level; an approximately similar degree of
      correlation was found for NT-proBNP and BP. CONCLUSION: Therefore, the performed
      statistical analysis determined correlations between the following factors: IL-6
      level, NTproBNP level, and one-year CHF progression.

PMID- 29466193
TI  - [The case of repeated syncopes in recurrent pulmonary embolism].
AB  - The article provides a case report of recurrent syncopal episodes in a 57-year
      old male patient. During a three-month period of recurrent syncope, the patient
      was managed by the family doctor and at pulmonology and cardiology departments
      for different diagnoses. Due to an uncertainty in diagnosis, the patient was
      moved to a hospital where he underwent echocardiographic examination and duplex
      scanning of right leg veins, which detected a 49.3 mm right leg venous thrombus
      with a free-floating head in the right common femoral vein. Retrospectively,
      recurrent pulmonary artery thromboembolism was diagnosed. Thrombectomy and
      ligation of the right superficial artery were performed; an approximately 17 cm
      long thrombus was removed; the anticoagulant treatment was administered with a
      beneficial effect.

PMID- 29466194
TI  - [The Role of the I/D Polymorphism of the ACE Gene in the Development of Atrial
      Fibrillation].
AB  - OBJECTIVE: To study associations of I / D polymorphism of the ACE gene with risk
      of atrial fibrillation (AF) with the aim of detecting groups of patients prone to
      development of this disease. MATERIALS AND METHODS: We examined 90 probands with
      confirmed diagnosis of AF and 144 their I, II, III degrees relatives. These
      families constituted a core group of our study. The control group comprised 100
      relatively healthy people without history of cardiovascular diseases. Methods
      used in all patients included clinical examination, electrocardiography,
      echocardiography, Holter ECG monitoring, veloergometry, transesophageal left
      atrial pacing, molecular-genetic tests. RESULTS: We found statistically
      significant predominance of genotype II homozygous carriers among probands with
      primary AF compared with the control group (30.0+/-7.2 % and 14.0+/-3.5 %,
      respectively; p=0.028). Homozygous carriers of DD genotype statistically
      significantly prevailed in the control group compared with group of probands with
      primary AF (36.0+/-4.8 % and 15.0 %+/-5.6 %; p=0.014). Carriers of homozygous
      genotype II for common allele statistically significantly prevailed among
      probands with secondary AF compared with the control group (34.0+/-6.7 % and
      14.0+/-3.5 %, respectively; p=0.004). Homozygous carriers of DD genotype for the
      rare allele statistically significantly prevailed among control subjects compared
      to probands with secondary AF (36.0+/-4.8 % and 10.0 %+/-4.2 %, respectively;
      p=0.001). CONCLUSION: Thus, compared with controls statistically significant
      preponderance of carriers of homozygous genotype II for common allele was found
      among probands with both primary and secondary AF. At the same time compared with
      probands there was a statistically significant predominance of homozygous
      carriers of DD genotype for the rare allele in the control group. Our findings
      suggest the heterogeneous nature of AF and confirm that DD genotype homozygosity
      can be protective against the development of AF.

PMID- 29466195
TI  - [Nerve Growth Factor in Patients With Arterial Hypertension: Neuropsychical,
      Hemodynamic, Metabolic Relationships].
AB  - AIM: To investigate the changes of serum nerve growth factor (NGF) level in
      patients with arterial hypertension (AH) and obesity in dependence on the degree
      of psycho-emotional stress and physical activity. MATERIALS AND METHODS: We
      examined 76 male patients with stage I and II AH with mean age 46.75+/-0.56 years
      (36 patients with and 40 without obesity). Control group consisted of 26
      individuals without AH, obesity, and cardiovascular diseases. All patients
      underwent ambulatory blood pressure (BP) monitoring. Serum concentrations of NGF
      beta-subunit and cortisol were determined by enzyme linked immunosorbent assay.
      For assessment of levels of psycho-emotional stress, reactive and personal
      anxiety, and physical activity we used Psychological Stress Measure (PSM-25), the
      Spielberger-Khanin questionnaire, and brief International Physical Activity
      Questionnaire (IPAQ), respectively. RESULTS: Level of NGF in patients with AH and
      obesity (0.94+/-0.28 rhog/ml) was higher than in non-obese patients with AH
      (0.21+/-0.06 rhog/ml; p=0.018) with highest figures in patients with insufficient
      physical activity and high level of psychoemotional stress. In all groups of
      patients there was unidirectional reverse correlation between serum NGF and
      cortisol levels. According to ambulatory BP monitoring, NGF level was inversely
      proportional to systolic and diastolic BP variability in patients with AH and
      obesity and in the control group. Reduced serum concentration of NGF was
      associated with increased levels of reactive and personal anxiety. CONCLUSION:
      Obtained data suggests that NGF plays an important role in complex multifactorial
      interactions between neuropsychic, cardiovascular and metabolic processes.

PMID- 29466197
TI  - [Assessment of Vascular Stiffness in Normotensive Patients With Familial
      Hypercholesterolemia].
AB  - AIM: to analyze parameters of vascular stiffness and augmentation index in
      patients with familial hypercholesterolemia (FH). MATERIALS AND METHODS: We
      compared parameters of vascular stiffness of 88 normotensive FH patients (mean
      age 41.95+/-1.43 years, 43 men [48.9 %]) and 68 subjects with normal blood lipid
      spectrum (mean age 37.58+/-1.02 years, 21 men [30.9 %]). FH was diagnosed
      according to the criteria of the Dutch Lipid Clinic Network. Examination included
      lipid profile, 24-hour blood pressure (BP) monitoring with assessment of arterial
      stiffness. RESULTS: Normotensive FH patients had higher pulse wave velocity (PWV)
      (7.99+/-0.17 m/s) in comparison with patients with normal lipid spectrum (6.87+/
      0.10 m/s), p.

PMID- 29466196
TI  - [Issues of Adipokine Regulation in Idiopathic Pulmonary Arterial Hypertension and
      Systemic Osteopenia].
AB  - PURPOSE: to determine the role of adipokines and vascular remodeling in formation
      of osteoporosis in idiopathic pulmonary arterial hypertension (IPAH). MATERIALS
      AND METHODS: Functional and hemodynamic parameters, bone mineral density (BMD) T
      score in lumbar spine (LS) and femoral neck (FN), blood serum levels of leptin,
      adiponectin, visfatin and endothelin-1 were measured in 27 patients with severe
      IPAH and 30 healthy volunteers. RESULTS: Half of IPAH patients had osteoporosis.
      Serum levels of leptin, adiponectin, visfatin and endothelin-1 in IPAH group were
      higher than in healthy volunteers. BMD T-score was directly related to results of
      6-minute walk test and inversely related to pulmonary vascular resistance (PVR).
      Circulating adiponectin and visfatin concentrations correlated with PVR;
      endothelin-1 concentration was directly related to pulmonary arterial systolic
      pressure, cardiac index and PVR. Relations between BMD T-score and circulating
      adiponectin, visfatin, and endothelin-1 were inverse. Positive correlations
      existed between serum adiponectin, visfatin and endothelin-1 levels. CONCLUSION:
      Results of our study confirm the important role of adipokine and endotheline
      dysregulation in development of hemodynamic disorders in severe IPAH and evidence
      for their possible involvement in formation of osteopenic syndrome.

PMID- 29466199
TI  - [Belenkov Yuriy Nikitich (To the 70th birthday)].

PMID- 29466198
TI  - [Diverticula and Congenital Aneurysms of the Left Ventricle: Anatomical Features,
      Pathophysiology, Clinical Presentation and Treatment Strategy].
AB  - Congenital aneurysms and diverticula of the left ventricle represent a rare group
      of anomalies in the spectrum of congenital heart disease. Although natural
      histories of these anomalies are considerably different and characterized by
      different rates of lifethreatening events, similarity of their clinical
      presentation and diagnostic criteria do not allow to differentiate this anomalies
      at routine examination. Data on etiology, methods of diagnosis and treatment
      published by various authors is controversial. In this review we present relevant
      aspects of etiology, pathophysiology and treatment strategy of patients with left
      ventricular diverticula and congenital aneurysms.

PMID- 29466200
TI  - [SGLT2 Inhibitors: Rationale and Perspectives of Use in Heart Failure].

PMID- 29466201
TI  - [Antiaggregants in Primary Prevention of Cardiovascular Diseases and Prevention
      of Atherothrombosis in Patients With Stable Ischemic Heart Disease: Aspects of
      Efficacy and Safety].
AB  - This review is devoted to the use of antiaggregants. We consider here
      pathogenesis of intraarterial thrombosis, mechanism of action of antiaggregants,
      and recommendations on the use of drugs of this class for primary prevention of
      cardiovascular diseases and prevention of atherothrombotic complications of
      stable ischemic heart disease. Information on mechanisms of development and
      causes of resistance to antiaggregants is also presented. Finally we discuss the
      problem of safety of therapy with antiaggregants, methods of lowering the risk of
      bleeding, and prevention of aspirin induced gastropathy.

PMID- 29466202
TI  - [Ivabradine in Modern Pharmacotherapy of Cardiovascular Diseases - Realities and
      Prospects].

PMID- 29466203
TI  - [Use of Highly Concentrated Polyunsaturated Fatty Acids for Prevention of
      Complications After Myocardial Infarction. Cost-Utility Analysis].
AB  - Use of highly concentrated ethyl esters of polyunsaturated fatty acids after
      myocardial infarction (MI) and in patients with heart failure was associated with
      lower mortality. The goal of this analysis was to perform cost-utility analysis
      of the use of highly concentrated ethyl esters of polyunsaturated fatty acids
      after MI (with help of a Markov model) and to find whether its use in some group
      of patients led to decrease in budget costs. As a result, we have shown that use
      of highly concentrated ethyl esters of polyunsaturated fatty acids after MI leads
      to increase in quality-adjusted life expectancy on 0.5 QALY, with incremental
      cost-effectiveness ratio of 105 thousand rubles per QALY, and net monetary
      benefit of 780.5 thousand rubles. In the patient subpopulation that receives
      highly concentrated ethyl esters of polyunsaturated fatty acids for arrhythmia
      prevention after coronary artery bypass the estimated decrease of budget cost
      varies between 6 and 50% depending on denominator used.

PMID- 29466204
TI  - [Myocardial Infarction Due to Coronary Artery Embolism].
AB  - Coronary artery embolism (CAE) takes an important place among non-atherosclerotic
      causes of acute myocardial infarction (AMI). The features of embolic AMI are
      difficulties in diagnostics and absence of evidence-based guidelines for the
      management of CAE. Purpose of this review - to present synthesis of available
      data on embolic AMI. We also report here three cases demonstrating new approaches
      to treatment of CAE.

PMID- 29466205
TI  - [Basic Principles of Periprocedural Management of Patients With Nonvalvular
      Atrial Fibrillation Receiving Anticoagulant Therapy: the Consensus Document of
      Experts of the American College of Cardiology].
AB  - The article contains an outline of the 2017 ACC Expert Consensus Decision Pathway
      for Periprocedural Management of Anticoagulation in Patients With Nonvalvular
      Atrial Fibrillation. This document considers in detail problems of necessity and
      safety of temporary interrupting of anticoagulation for the period of procedure,
      main principles of interruption and restarting anticoagulant therapy after
      procedure, indications to the transitional (bridging) therapy in the
      periprocedural period, as well as possible strategies of periprocedural
      management of patients in dependence of risk of bleeding and thromboembolic
      complications. This Expert Consensus Decision Pathway refer to the periprocedural
      use of both oral (vitamin K antagonists, new oral anticoagulants) and parenteral
      (unfractionated and low-molecular-weight heparins) anticoagulants.

PMID- 29466206
TI  - [Carotid Plaque Instability in Patients With Acute Coronary Syndrome as Assessed
      by Ultrasound Duplex Scanning].
AB  - AIM: to study carotid plaques structure in patients with acute coronary syndrome
      by ultrasound duplex scanning. MATERIALS AND METHODS: We included in this
      study143 patients with acute coronary syndrome (ACS) aged 32-83 years and 28
      patients with documented coronary heart disease (CHD) aged 46-83 years. Duplex
      scanning of carotid arteries was carried out with Philips iU22 ultrasound system
      and L9-3 linear array transducer. Atherosclerotic plaques in CCA, CCA
      bifurcation, and ICA from right and left side were investigated. Off-line
      analysis of B-mode images and plaque gray scale median (GSM) was performed with
      computer semiautomated workstation MultiVox. RESULTS: 378 plaques of ACS and 59
      plaques of CHD patients were studied. We assessed traditional (heterogenous
      structure, hypoechogenic component, irregular plaque surface) as well as
      additional (positive remodeling, "layered" structure of plaque, local
      calcification) criteria of plaque instability. In ACS compared with CHD group
      there were more plaques with hypoechogenic component (43.4 and 28.8%, p=0.0459),
      heterogenous structure (77.8 and 64.4%, p=0.0327), irregular surface including
      irregularities more than 2.0 mm (22.5 and 6.8%, p=0.0048, respectively). There
      was significant difference in "layered" structure (55.7 and 35.8%, p=0.0011) and
      insignificant difference in positive remodeling (16.3 and 7.5%, p=0.06,
      respectively). There were no differences of GSM value (53.1 and 57.2, p=0.24) and
      local calcification (23.2 and 24.5%, p=0.23, respectively). CONCLUSION: In our
      study ultrasound duplex scanning revealed that signs of plaque instability in
      carotid arteries in patients with ACS were more frequent than in patients with
      stable CHD. The newly introduced parameter "layered" structure of atherosclerotic
      plaque was found to be most significant.

PMID- 29466207
TI  - [Hypertrophic Cardiomyopathy and Ischemic Heart Disease. Variants of Combination
      Pathology].
AB  - The issues of epidemiology and pathophysiology of hypertrophic cardiomyopathy
      (HCMP), as well as the search for its additional clinical-instrumental and
      genetic markers, environmental factors capable to influence the formation of its
      clinical variant and prognosis are subjects of great interest to the modern
      scientific community. Besides genetic markers of main neurohumoral systems, and
      morphofunctional parameters of intracardiac hemodynamics clinical course of the
      disease is influenced by a complex of concomitant pathology including ischemic
      heart disease (IHD), joining of which is possible in 10% of cases. IHD
      substantially aggravates course of HCMP and hampers selection of medical therapy.
      It should be noted that prognosis of primary hypertrophies is affected by
      episodes of ischemia of complex genesis and addition of IHD significantly
      increases risk of sudden death in these patients.

PMID- 29466208
TI  - [Gender Specific Characteristics of Ventricular-Atrial Remodeling in Recurrent
      Atrial Fibrillation in Ischemic Heart Disease Patients With Arterial
      Hypertension].

PMID- 29466209
TI  - [Awareness of the Risk Factors for Cardiovascular Disease in Different Types of
      Hospitalized Medical Patients].
AB  - OBJECTIVE: to study medical awareness of cardiovascular risk factors (FR) in
      hospitalized patients of the cardiac and internal medicine units (CU and IMU).
      MATERIALS AND METHODS: A total of 100 patients from CU (n=50) and IMU (n=50) of a
      Moscow city hospital were included into the survey. The patients were interviewed
      during the I-II days of hospital stay. A special questionnaire was developed
      including socio-demographic and clinical indicators, open questions on the
      knowledge of traditional cardiovascular RFs and their target values. RESULTS:
      Patients of both units did not differ in gender and age. The survey revealed an
      extremely low awareness of major cardiovascular RFs of patients in both units:
      practically none of them indicated as RFs for cardiovascular disease elevated
      cholesterol (0 and 2 %, respectively, p>0.05) and blood pressure (0 % and 2 %,
      respectively, p>0.05). The majority of patients in both units (74 and 68 %,
      respectively, p>0.05) reported only 1-2 RFs. Patients in both units often
      believed that stress is the main cardiovascular RF (66 % and 50 %, respectively,
      p>0.05). CONCLUSION: The survey revealed a low awareness of cardiovascular RFs in
      different types of medical patients at time of hospital admission.

PMID- 29466210
TI  - [Elevated Level of the Natriuretic Peptide Among Adult Population in Regions
      Participating in the ESSE-RF Study and Its Association With Cardiovascular
      Diseases and Risk Factors].
AB  - AIM: to study associations between elevated blood plasma concentration of N
      terminal pro-brain natriuretic peptide (NT-proBNP), risk factors and
      cardiovascular diseases (CVD) in samples of adult population of Russian
      Federation (RF) aged 25-64 years. MATERIALS AND METHODS: We analyzed data of
      examination of representative samples of population of 5 regions of RF obtained
      within the framework of the multicenter ESSE-RF study (2012-2013). Number of
      examined subjects was 8 077 (3 176 men). Methods included use of standard
      questionnaire, measurements of height, body mass, blood pressure (BP), and plasma
      NT-proBNP level. The following CVD were included into analysis: arterial
      hypertension (AH), ischemic heart disease (IHD), atrial fibrillation (AF), and
      stroke. RESULTS: Women compared to men had higher NT-proBNT concentration was
      higher in women compared to men, in both genders it rose with age. Overall 17.9 %
      of examinees had elevated NT-proBNT levels (14.2 and 20.3 % among men and women,
      respectively). Elevated NTproBNP level was associated in men with age, myocardial
      infarction, angina pectoris, ischemic ECG changes, left ventricular hypertrophy,
      AF, bradycardia, smoking, in women with age, IHD, ischemic ECG changes, AF,
      bradycardia, heart rate >=80 bpm, BP >=160/95 mm Hg. CONCLUSION: In studied RF
      population elevated NT-proBNP level was significantly associated with gender,
      age, smoking, and CVD.

PMID- 29466212
TI  - ?

PMID- 29466211
TI  - [The Role of Macrophages in Repair of Injured Myocardium and Perspectives of
      Metabolic Reprogramming of Immune Cells for Myocardial Post-Infarction Recovery].
AB  - A new trend in modern experimental cardiology is the development of approaches to
      correction of reparation after myocardial infarction (MI) with the use of
      specific effects on immune cells. One of the main targets for such interventions
      is the process of macrophage's polarization in the infarction zone.
      Proinflammatory M1-macrophages contribute to hampered myocardial repair, in
      contrast to M2-macrophages that promote regeneration. Currently, there are two
      main ways of targeted delivery of agents necessary for macrophage reprogramming -
      inlipoid and inglycan-encapsulated particles. As modulating agents, small
      interfering RNA and other genetic constructions are usually used. Both these
      approaches are currently awaiting their translation into cardiology. The most
      physiological approach to reprogramming of immune cells may consist in attempts
      to switch the metabolism of the immune cell from glycolytic to oxidative, which
      allows macrophages to switch from M1 to M2 phenotype. Among possible targets for
      macrophage reprogramming, it is worthwhile to isolate the protein complex mTORC1,
      the blocking of which promotes oxidative metabolism, and the transcription factor
      HIF-1alpha, the blocking of which also facilitates the switching of the
      metabolism from glycolytic to oxidative one.

PMID- 29466213
TI  - [24-Hour Arterial Pressure Variability: Prognostic Significance, Methods of
      Evaluation, Effect of Antihypertensive Therapy].
AB  - We discuss in this article problems of prognostic significance of 24-hour
      arterial pressure variability (24hAPV), as well as the role of 24hAPV in
      development and progression of various target organs damage by arterial
      hypertension. We also present literature data on impact of various regimens of
      antihypertensive therapy on 24hAPV, and on ability of fixed-dose
      perindopril/amlodipine to lower 24-hAPV.

PMID- 29466215
TI  - [New Possibilities in the Treatment of Patients With Stable Manifestations of
      Atherothrombosis].

PMID- 29466214
TI  - [Sudden Cardiac Death in Patients With Ischemic Heart Disease: From Mechanisms to
      Clinical Practice].
AB  - Ischemic heart disease (IHD) and acute coronary syndrome are the main cause of
      sudden cardiac death (SCD). Incidence of SCD in patients after myocardial
      infarction (MI) is 4-6-fold higher than in general population. The review focuses
      on electrophysiological changes during acute myocardial ischemia and mechanisms
      of myocardial electromechanical remodeling in remote period after MI. Current
      data on arrhythmia substrates and triggers are presented. Nowadays, the main
      guide for implantable cardioverter-defibrillator (ICD) use for primary prevention
      of SCD is reduced left ventricular ejection fraction. The significance of this
      parameter has been repeatedly demonstrated in large randomized studies. However,
      the use of a single indicator cannot solve the problem. In this review we present
      analysis of modern additional predictors of fatal arrhythmias which are available
      in clinical practice, as well as the perspective for further research of this
      highly important scientific, clinical, and social problem.

PMID- 29466216
TI  - [Clinical Aspects of Interventional Treatment of a Patient With Atrial
      Fibrillation Combined With Resistant Arterial Hypertension by the Method of
      Radiofrequency Ablation in Renal Arteries and Left Atrium].

PMID- 29466217
TI  - [Takotsubo Cardiomyopathy as a Consequence of Myocardial Infarction. It is
      Possible?]
AB  - Takotsubo cardiomyopathy (TCM) is a well-known complication of many conditions
      associated with emotional or physical stress. Abnormal catecholamine release has
      been hypothesized to be the main cause of TCM. Myocardial infarction (MI) is
      associated with release of large amounts of catecholamines. We present here two
      cases in which patients simultaneously suffered from acute MI and TCM. In these
      elderly women without prior history of severe somatic diseases we have not
      revealed any external stressing factor responsible for the initiation of the
      disease. Therefore, we have considered primary coronary event (acute MI) to be a
      triggering factor of TCM manifestation.

PMID- 29466218
TI  - [Structural and Functional Properties of the Left Atrium in Healthy Volunteers
      and Patients With Atrial Fibrillation: Data of Magnetic Resonance Imaging].
AB  - BACKGROUND: in the recent years, there has been an increasing number of
      publications postulating that data on left atrial (LA) structure obtained by late
      gadolinium enhancement magnetic resonance imaging (LGE MRI) can improve the
      management of patients with atrial fibrillation (AF). At the same time, similar
      data regarding healthy LA myocardium is limited. AIM: to assess structural and
      functional properties of LA in healthy volunteers (HV) using cardiac magnetic
      resonance (CMR) (including LGE MRI); to compare these properties in patients with
      AF and HV. MATERIALS AND METHODS: We included in this study 53 patients with AF
      (28 without signs of cardiovascular disease, 28 with hypertension) and 23 HV of
      similar age. All enrolled persons underwent MRI. Cine-MRI was used to assess end
      diastolic volume of LA (LA EDV), LA ejection fraction (LA EF), left ventricular
      diastolic index (LV DI). High resolution LGE MRI was performed 15-20 min after
      gadoversetamide injection using IR 3D gradient echo pulse sequence with fat
      saturation (TI 290-340 ms, TE 2.44 ms, TR 610-1100ms). On obtained images LA was
      segmented semiautomatically. LA fibrosis quantification was performed using
      developed software LGE Heart Analyzer. The extent of fibrosis was represented as
      percent of LA myocardium volume. Fibrosis location was determined on
      reconstructed rotating 3D LA model. RESULTS: Compared with patients HV had lower
      LA EDV (59 [54; 78] ml and 79 [65.5; 86.6] ml, r=0.043, respectively), higher LA
      EF (56.1 [49; 63.2] % and 44.5 [34.5, 54.5] %, r=0.03, respectively), and lower
      extent of LA fibrosis (0.7 [0.05; 3.5] % and 9.1 [1.7; 18] %, r.

PMID- 29466219
TI  - [Effect of Type 2 Diabetes Mellitus on Five-Year Survival of Patients
      Hospitalized Because of Acute Decompensated Heart Failure].
AB  - OBJECTIVE: To assess the impact of type 2 diabetes mellitus (T2DM) on prognosis
      of patients hospitalized because of acute decompensated heart failure (ADHF).
      MATERIALS AND METHODS: We analyzed data of the hospital register of ADHF which
      comprised information on 735 patients (254 [35%] with T2DM) consecutively
      admitted in 2010-2011. Median follow-up was 1790 days. RESULTS: The presence of
      T2DM was associated with increased risk of death: during the index
      hospitalization due to ADHF (hazard ratio [HR] 1.7, 95% confidence interval [CI]
      1.0-2.8), within 18 months (HR 1.4, 95% CI 1.0-1.8), and within 5 years (HR 1.3,
      95% CI 1.0-1.5). CONCLUSIONS: T2DM is common among acute decompensated heart
      failure patients (up to 35% of cases). T2DM is an independent risk factor of
      death during the index hospitalization and over the next 18 months and 5 years.

PMID- 29466220
TI  - [Head to Head Comparison of Suppression of Tumorogenicity 2 and Copeptin
      Significance for Prognosis of Patients After Acute Heart Failure Decompensation].
AB  - PURPOSE: To assess the suppression of tumorogenicity 2 (ST2) and copeptin
      significance for risk stratification of patient (pts) with acute decompensated
      heart failure (ADHF) during long-term follow-up compared with traditional risk
      factors. METHODS: We included in a prospective study 159 pts with ADHF. Blood
      samples to determine copeptin, sST2, NT-proBNP and hsTnT concentration were
      collected at admission and at discharge from the hospital. Serial determination
      of biomarker concentration was performed at 3, 6 and 12 months of follow-up. The
      combined primary end point of the trial included cardiovascular (CV) death,
      hospitalization due to HF, episodes of HF deterioration requiring additional
      intravenous diuretics and CV death with successful resuscitation. RESULTS: During
      1-year follow-up (295.3+/-113.2 days) 56 pts (35.2%) had 78 (49.1%)
      cardiovascular events. Biomarker concentrations in low risk pts (without CV
      events) were significantly lower compared with high risk pts (with CV events).
      Discharge copeptin and NT-proBNP values were comparable for pts risk
      stratification: AUC=0.727 (95% CI 0.637-0.816), r.

PMID- 29466221
TI  - [Effects of High-Dose Statin Therapy on Cognitive Functions and Quality of Life
      in Very High Cardiovascular Risk Patients].
AB  - AIM: To investigate the effects of intensive lipid-lowering therapy on cognitive
      functions and quality of life in patients (pts) with very high cardiovascular
      risk. MATERIAL AND METHODS: In 93 pts (58 men, 63.2+/-9.5 years old with history
      of clinically evident cardiovascular disease and fasting low-density lipoprotein
      cholesterol (LDL-C) >1.8 mmol/l or non-high-density lipoprotein cholesterol (non
      HDL-C) >2.6 mmol/l the mental status and quality of life were assessed before and
      after 6 months of therapy with atorvastatin 80 mg/day. The Montreal Cognitive
      Assessment (MoCA) scale and Questionnaire SF-36 (russian version) were used to
      evaluate cognitive functions and quality of life. RESULTS: 59 (63%) pts had
      cognitive dysfunction (less than 26 scores by MoCA scale). We observed
      significant difference in cognitive status between pts >=65 and.

PMID- 29466222
TI  - [Randomized Comparison of Two Approaches to Initial Warfarin Dosing: Time in
      Therapeutic Range of International Normalized Ratio During Hospitalization].
AB  - AIM: To perform a randomized, open-label comparison of average time in
      therapeutic range (TTR) of international normalized ratio (INR) using two
      approaches to initial warfarin dosing during hospitalization: the standard method
      and the one using individual patient characteristics (clinical algorithm - the
      studied approach). MATERIALS AND METHODS: We randomly assigned 60 patients with
      different indications for vitamin K antagonist therapy to the studied approach
      (n=31, intervention group) or to the standard method (n=29, control group). A
      target INR range for all patients was 2.0 to 3.0. RESULTS: The average TTR and
      portions of INR values within target range during the whole time of drug dosing
      turned out to be small. TTR was 22.4% with standard method and 21.4% with
      clinical algorithm, which was well below desired 60%. CONCLUSION: The
      opportunities for achieving target INR in inpatient settings, regardless of
      warfarin dosing regimen, are limited.

PMID- 29466224
TI  - ?

PMID- 29466223
TI  - [Quality of Life of Patients With the Ascending Aorta Aneurism After Valve-
      Sparing Surgery].

PMID- 29466225
TI  - [Current Echocardiographic Techniques for Evaluation of the Right Ventricle].
AB  - The review is dedicated to the new echocardiographic techniques in the assessment
      of right ventricular (RV) function, such as two-dimensional speckle tracking and
      determining the RV volume by a three-dimensional model. Subclinical changes in RV
      function are of great importance for the diagnosis and assessment of prognosis of
      multiple cardiovascular as well as non-cardiac pathologies. Two-dimensional
      speckle tracking allows to assess longitudinal strain of the RV myocardium and to
      detect pathological changes before their clinical manifestations. Three
      dimensional echocardiography enables calculation of the RV ejection fraction,
      what was not possible before with the use of ultrasound. Currently, both methods
      are promising for a comprehensive assessment of RV function.

PMID- 29466226
TI  - [The Role of MicroRNA in Atherogenesis].
AB  - This review provides modern data on the spectrum and the functional significance
      of micro-RNAs involved in atherogenesis and on some regulatory mechanisms that
      ensure the functioning of this class of molecules. We also outline some examples
      of micro-RNAs use as diagnostic and therapeutic targets.

PMID- 29466227
TI  - [Lizinopril in the Treatment of Arterial Hypertension].
AB  - Despite availability of a wide selection of antihypertensive drugs, only a small
      portion of patients with arterial hypertension are treated effectively.
      Angiotensin converting enzyme inhibitors (ACEI) are considered drugs of first
      choice for starting therapy of uncomplicated arterial hypertension. Among large
      number of representatives of this class lisinopril deserves special attention as
      one of best known and well-studied ACEIs. Wide spectrum of activity and proven
      organoprotective qualities of lisinopril allow to use it a variety of situations.

PMID- 29466228
TI  - [Diagnosis and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary
      Syndrome. Part 2].

PMID- 29466229
TI  - Statistical Methodology of the National Immunization Survey, 2005-2014.
AB  - The National Immunization Survey (NIS) family of surveys includes NIS-Child,
      which monitors vaccination coverage for the U.S. population of children aged 19
      35 months; NIS- Teen, which monitors vaccination coverage for the U.S. population
      of adolescents aged 13-17; and NIS-Flu, which monitors influenza vaccination
      coverage for the U.S. population of children aged 6 months through 17 years. This
      report describes the methods used in this family of surveys during the 2005-2014
      period.

PMID- 29466230
TI  - Linkage of 1999-2012 National Health Interview Survey and National Health and
      Nutrition Examination Survey Data to U.S. Department of Housing and Urban
      Development Administrative Records.
AB  - Objectives This report presents the development, plan, and operation of the 2011
      2012 National Survey of Children's Health, a module of the State and Local Area
      Integrated Telephone Survey, conducted by the National Center for Health
      Statistics. Funding was provided by the Maternal and Child Health Bureau, Health
      Resources and Services Administration. The survey was designed to produce
      national and state prevalence estimates of the physical and emotional health of
      children aged 0-17 years, as well as factors that may relate to child well-being
      including medical homes, family interactions, parental health, school and after
      school experiences, and neighborhood characteristics.

PMID- 29466231
TI  - Transcytosis of payloads that are non-covalently complexed to bispecific
      antibodies across the hCMEC/D3 blood-brain barrier model.
AB  - A transcellular shuttle system was generated for the delivery of non-covalently
      linked payloads across blood-brain barrier (BBB) endothelial cells. Transcytosis
      enabling shuttles are composed of bispecific antibodies (bsAbs) that
      simultaneously bind transferrin receptor (TfR) and haptens such as digoxigenin or
      biocytinamide. Haptenylated payloads are attached to these vehicles via non
      covalent hapten-antibody complexation. This enables targeting to and
      internalization into human BBB-derived microvascular endothelial hCMEC/D3 cells.
      In contrast to other shuttles, this system does not require special affinities or
      formats of their TfR-binding moieties for transcytosis and subsequent release.
      Non-covalent payload complexation to bsAb is flexible and robust, works for a
      multitude of payloads and enables separation of payloads from shuttles during
      transcytosis. Released payloads can enter the brain without connected bsAb
      entities, minimizing potential interference with distribution or functionality.
      Intracellular separation of shuttle and payload and recycling to cell surfaces
      may also enable recharging of the cell-bound BBB shuttle with payload for
      subsequent (merry-go-round) transport cycles.

PMID- 29466232
TI  - Analytical performance of an automated volumetric flow cytometer for quantitation
      of T, B and natural killer lymphocytes.
AB  - BACKGROUND: Quantitation of lymphocyte subsets (B cells, T cells, CD4 and CD8 T
      cells and NK cells) classically relies on quantitation of lymphocytes and
      immunophenotyping by flow cytometry. AQUIOS CL (Beckman Coulter) is a fully
      automated system that performs an onboard volumetric cell count, automatically
      processes the sample (staining, lysing and fixation) and analyzes the results. We
      compared AQUIOS CL to a dual-platform analysis and evaluated analytical
      performance. METHODS: We evaluated precision, sample stability, inter-sample
      carryover, linearity and interpanel consistency. AQUIOS CL was compared to a dual
      platform method (Sysmex XE-5000 and BD FACSCanto-II). A total of 113 patient
      samples were included: 45 from posttransplant patients, 44 from children and 24
      random routine samples. The degree of automation was scored through the need of
      manual revisions triggered by AQUIOS CL run notifications and run flags. RESULTS:
      Intrarun and interrun variability was <9.1% with dedicated control material and
      <32.1% with patient samples. Relative values of lymphocyte subsets could be
      determined up to 48 h after venipuncture when the sample was kept at room
      temperature. There was no carryover and good linearity. Interpanel consistency
      was 3.3% for relative values and 9.4% for absolute values. Method comparison
      showed good analytical correlation between AQUIOS CL and a dual-platform method.
      Thirty-five percent of the samples triggered a run notification. In 74% of these
      samples, the results could be accepted without intervention, so in 26% of all
      samples, an unnecessary notification was generated. CONCLUSIONS: AQUIOS CL allows
      for reliable fully automated immunophenotyping of lymphocyte subset quantitation.
      Gating algorithms could be further improved.

PMID- 29466233
TI  - Anti-streptavidin IgG antibody interference in anti-cyclic citrullinated peptide
      (CCP) IgG antibody assays is a rare but important cause of false-positive anti
      CCP results.
AB  - BACKGROUND: The detection of anti-cyclic citrullinated peptide (anti-CCP) IgG
      antibodies in blood is mainly used for the diagnosis of rheumatoid arthritis.
      Falsely elevated anti-CCP IgG antibodies due to anti-streptavidin IgG antibodies
      were suspected in our laboratory. METHODS: In this study, we evaluated, in a
      standardized approach, the prevalence of anti-streptavidin IgG antibodies in a
      primary care setting and the effect of anti-streptavidin IgG antibodies on anti
      CCP IgG assays from three different important commercial manufacturers (Abbott,
      Roche Diagnostics, Thermo Fisher Scientific). Three different populations were
      consecutively and prospectively studied: serum samples from 1000 ambulatory
      patients, 286 serum samples from patients for which anti-CCP was requested and 89
      serum samples from patients which had previously given a positive anti-CCP result
      on Architect(r) i2000. RESULTS: The frequency of confirmed anti-streptavidin IgG
      positive samples detected in this study was 0.6% (8/1375). Anti-CCP IgG was
      determined on the eight samples with confirmed anti-streptavidin IgG antibodies:
      with the Cobas(r) method, seven positive anti-CCP results were observed and five
      positive anti-CCP results with the Architect(r) method. No positive anti-CCP IgG
      results were obtained with the EliATM method. Rheumatoid factor was negative in
      these eight samples. CONCLUSIONS: Anti-streptavidin IgG antibodies rarely cause
      false-positive results in some anti-CCP assays. However, despite being an
      infrequent assay problem, it could possibly lead to diagnostic confusion or even
      an incorrect diagnosis of rheumatoid arthritis.

PMID- 29466234
TI  - Bicarbonate interference on cobas 6000 c501 chloride ion-selective electrodes.

PMID- 29466235
TI  - White and beige adipocytes: are they metabolically distinct?
AB  - The white adipose tissue (WAT) exhibits great plasticity and can undergo
      "browning" and acquire features of the brown adipose tissue (BAT), which takes
      place following cold exposure, chronic endurance exercise or beta3-adrenergic
      stimulation. WAT that underwent browning is characterized by the presence of
      "beige" adipocytes, which are morphologically similar to brown adipocytes,
      express uncoupling protein 1 (UCP1) and are considered thermogenically competent.
      Thus, inducing a BAT-like phenotype in the WAT could promote energy dissipation
      within this depot, reducing the availability of substrate that would otherwise be
      stored in the WAT. Importantly, BAT in humans only represents a small proportion
      of total body mass, which limits the thermogenic capacity of this tissue.
      Therefore, browning of the WAT could significantly expand the energy-dissipating
      capacity of the organism and be of therapeutic value in the treatment of
      metabolic diseases. However, the question remains as to whether WAT indeed
      changes its metabolic profile from an essentially fat storage/release compartment
      to an energy dissipating compartment that functions much like BAT. Here, we
      discuss the differences with respect to thermogenic capacity and metabolic
      characteristics between white and beige adipocytes to determine whether the
      latter cells indeed significantly enhance their capacity to dissipate energy
      through UCP1-mediated mitochondrial uncoupling or by the activation of
      alternative UCP1-independent futile cycles.

PMID- 29466236
TI  - Mentoring as a Knowledge Translation Intervention for Implementing Nursing
      Practice Guidelines: A Qualitative Study.
AB  - An interpretive descriptive qualitative study was conducted to explore the
      characteristics and outcomes of mentoring used for implementing nursing practice
      guidelines. We interviewed six mentees, eight mentors, and four program leaders
      who were involved in the Registered Nurses' Association of Ontario fellowship
      program in Ontario, Canada. Inductive content analysis was used and study rigor
      was verified using triangulation of findings and member checking. Mentors were
      described as accessible, dedicated, and having expertise; mentees were described
      as enthusiastic, self-directed, and having mixed levels of expertise. The
      mentoring process included building relationships, developing learning plans, and
      using teaching and learning activities guided by learning plans to support
      development of mentees. Mentoring was described as positively impacting mentoring
      relationships, mentees, mentors, and organizations. A central feature of this
      fellowship program was the learning plan used to identify mentees' needs, guide
      mentoring activities, and monitor measureable outcomes.

PMID- 29466237
TI  - The State of Knowledge Regarding the Use of Simulation in Pre-Licensure Nursing
      Education: A Mixed Methods Systematic Review.
AB  - This project is a mixed-methods systematic review on the use of simulation in pre
      licensure nursing. This research question guided this review: What is the best
      evidence available upon which to base decisions regarding the use of simulation
      experiences with pre-licensure nursing students? Searches of CINAHL Plus with
      Full Text, MEDLINE, and ERIC were performed to identify relevant literature.
      These searches yielded 1220 articles. After duplicates were removed and titles
      and abstracts were reviewed for relevance to the inclusion criteria, the
      remaining 852 articles were independently assessed for quality by pairs of
      researchers. Forty-seven articles were retained. Findings were grouped into
      research using high-, medium-, and low-fidelity simulations and a group where
      researchers included several or all types of simulation. The conclusion is that
      insufficient quality research exists to guide educators in making evidence-based
      decisions regarding simulation. More rigorous and multi-site research is needed.

PMID- 29466238
TI  - Role of reactive oxygen species-total antioxidant capacity status in Telfairia
      occidentalis leaves-associated spermatoprotective effect: a pointer to fatty
      acids benefit.
AB  - Background The present study used reactive oxygen species (ROS)-total antioxidant
      capacity (TAC) score to understand the role of redox status on the effect of
      Telfairia occidentalis (TO) on testicular parameters. The fatty acids (FAs)
      components of methanol extract of TO (METO) and its fractions were also
      identified with gas chromatography-mass spectrometry. Methods A total of 66 male
      Wistar rats were randomly divided in a blinded fashion into six oral treatment
      groups as follows: group I (control, n=6) received 10% ethanol (vehicle for TO
      administration). Groups II to VI (n=12 rats each) were subdivided into two
      treatment subgroups (n=6 each) that received 200 mg/kg and 600 mg/kg of METO and
      its chloroform, petroleum ether, acetone, and ethanol fractions, respectively.
      All treatments lasted for 30 days. Results The major FAs detected in TO were
      myristic, palmitic, oleic, linoleic, linolenic, and stearic acids including their
      esters. Both doses of METO and its fractions increased the semen parameters, TAC
      and ROS-TAC scores but decreased the ROS when compared with control. Conclusions
      Using the ROS-TAC score, this study suggests that TO-associated improvement in
      semen parameters might be partly mediated by a reduction in free radical
      generation, and that the FAs present in TO might be involved in its
      spermatoprotective effect.

PMID- 29466239
TI  - Evaluation of basal sex hormone levels for activation of the hypothalamic
      pituitary-gonadal axis.
AB  - BACKGROUND: This study aimed to identify the predictive value of basal sex
      hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in
      girls. METHODS: Gonadotropin-releasing hormone (GnRH) stimulation tests were
      performed and evaluated in a total of 1750 girls with development of secondary
      sex characteristics. Correlation analyses were conducted between basal sex
      hormones and peak luteinizing hormone (LH) levels >=5 IU/L during the GnRH
      stimulation test. Receiver operating characteristic (ROC) curves for basal levels
      of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the
      GnRH stimulation test were plotted. The area under the curve (AUC) and 95%
      confidence intervals (CIs) were measured for each curve. RESULTS: The maximum AUC
      value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by
      basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI:
      0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff
      value of basal LH levels associated with a positive response of the GnRH
      stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of
      76.3% from the ROC curves when Youden's index showed the maximum value. When 100%
      of patients had peak LH levels >=5 IU/L, basal LH values were >2.72 IU/L, but the
      specificity was only 5.45%. CONCLUSIONS: Increased basal LH levels are a
      significant predictor of a positive response during the GnRH stimulation test for
      assessing activation of the HPG axis in most girls with early pubertal signs.

PMID- 29466240
TI  - Growth velocity and biological variables during puberty in achondroplasia.
AB  - BACKGROUND: Achondroplasia is the most common form of inherited disproportionate
      short stature. Cross-sectional design studies of height show that, during
      childhood, height standard deviation scores (SDS) declines steadily and reaches a
      mean adult height at -6.42 and -6.72 SDS. However, there is a lack of knowledge
      about longitudinal growth and biological variables during puberty for children
      with achondroplasia. Here we report the growth velocity and biological parameters
      during puberty in children with achondroplasia. METHODS: The study was an
      observational, cohort study. A total of 23 patients, 15 girls and eight boys with
      achondroplasia, who reached adult size were included. Growth data was collected
      from mid-childhood until final height by the same trained observer. Individual
      growth curves were estimated by fitting the Preece-Baines model 1 (PB1) to each
      individual's height for age data. Pubertal development was scored on Tanner scale
      on each visit. RESULTS: In boys with achondroplasia the mean adult height was
      129.18 cm. Age and velocity at peak velocity in puberty were 13.89 years and 4.86
      cm/year, respectively. The adolescent gain was 20.40 cm. Mean age at genital
      development 2 and 5 were 12.16 (0.60) and 14.97 (0.88), respectively. In girls
      the mean adult height was 118.67 cm. Age and velocity at peak velocity in puberty
      were 11.45 years and 4.40 cm/year, respectively. The adolescent gain was 19.35
      cm. Mean age at breast 2 and 4 were 10.20 (1.24) and 12.49 (1.07), respectively.
      CONCLUSIONS: Children with achondroplasia experienced an adolescent growth spurt,
      which was similar in shape and half the magnitude of the non-achondroplasia
      population.

PMID- 29466241
TI  - In iodine-induced thyrotoxicosis, steroid therapy today could keep the surgical
      knife at bay.
AB  - BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) type 2, characterized as a
      destructive thyroiditis, is well described in the medical literature; however,
      iodine-induced thyrotoxicosis (IIT) is not, though the latter has similar
      features and can be managed similarly. CASE PRESENTATION: We present a 17-year
      old female who presented with a history of an intermittent goiter with thyroid
      function tests (TFTs): thyroid-stimulating hormone (TSH)<0.015 (0.4-4 MUU/mL),
      free thyroxine (T4)>=6 (0.7-2.1 ng/dL) and total triiodothyronine (T3) 651 (50
      200 mg/dL). Thyroid antibodies were all negative. Despite methimazole therapy for
      6 weeks, hyperthyroidism proved refractory to medical management. 123I scan
      uptake was suppressed. With hyperthyroidism being recalcitrant to therapy, a
      nutritional history revealed consumption of an iodine supplement containing at
      least 7 times the recommended daily allowance (RDA) for 5 years, contributing to
      the Jod-Basedow phenomenon. Urinary spot and 24-hour urinary iodine were both
      elevated. Though a surgical consult was obtained, surgery was cancelled once TFTs
      improved and then normalized with steroid therapy. The TFTs and urinary iodine
      levels remained normal post steroid therapy. CONCLUSIONS: We suggest that in
      addition to the need for a thorough nutritional history, a trial of
      corticosteroids should be utilized in the management of IIT which can present
      with findings similar to AIT type 2 which is recalcitrant to thionamide therapy.
      If successful, corticosteroids may delay or prevent surgical management thus
      avoiding possible complications with the latter approach.

PMID- 29466242
TI  - Mindfulness and meditation: treating cognitive impairment and reducing stress in
      dementia.
AB  - This study investigates the relationship between mindfulness, meditation,
      cognition and stress in people with Alzheimer's disease (AD), dementia, mild
      cognitive impairment and subjective cognitive decline. Accordingly, we explore
      how the use of meditation as a behavioural intervention can reduce stress and
      enhance cognition, which in turn ameliorates some dementia symptoms. A narrative
      review of the literature was conducted with any studies using meditation as an
      intervention for dementia or dementia-related memory conditions meeting inclusion
      criteria. Studies where moving meditation was the main intervention were excluded
      due to the possible confounding of exercise. Ten papers were identified and
      reviewed. There was a broad use of measures across all studies, with cognitive
      assessment, quality of life and perceived stress being the most common. Three
      studies used functional magnetic resonance imaging to measure functional changes
      to brain regions during meditation. The interventions fell into the following
      three categories: mindfulness, most commonly mindfulness-based stress reduction
      (six studies); Kirtan Kriya meditation (three studies); and mindfulness-based
      Alzheimer's stimulation (one study). Three of these studies were randomised
      controlled trials. All studies reported significant findings or trends towards
      significance in a broad range of measures, including a reduction of cognitive
      decline, reduction in perceived stress, increase in quality of life, as well as
      increases in functional connectivity, percent volume brain change and cerebral
      blood flow in areas of the cortex. Limitations and directions for future studies
      on meditation-based treatment for AD and stress management are suggested.

PMID- 29466243
TI  - G protein-coupled receptor-receptor interactions give integrative dynamics to
      intercellular communication.
AB  - The proposal of receptor-receptor interactions (RRIs) in the early 1980s
      broadened the view on the role of G protein-coupled receptors (GPCR) in the
      dynamics of the intercellular communication. RRIs, indeed, allow GPCR to operate
      not only as monomers but also as receptor complexes, in which the integration of
      the incoming signals depends on the number, spatial arrangement, and order of
      activation of the protomers forming the complex. The main biochemical mechanisms
      controlling the functional interplay of GPCR in the receptor complexes are direct
      allosteric interactions between protomer domains. The formation of these
      macromolecular assemblies has several physiologic implications in terms of the
      modulation of the signaling pathways and interaction with other membrane
      proteins. It also impacts on the emerging field of connectomics, as it
      contributes to set and tune the synaptic strength. Furthermore, recent evidence
      suggests that the transfer of GPCR and GPCR complexes between cells via the
      exosome pathway could enable the target cells to recognize/decode transmitters
      and/or modulators for which they did not express the pertinent receptors. Thus,
      this process may also open the possibility of a new type of redeployment of
      neural circuits. The fundamental aspects of GPCR complex formation and function
      are the focus of the present review article.

PMID- 29466244
TI  - Biomarkers for detection, prognosis and therapeutic assessment of neurological
      disorders.
AB  - Neurological disorders have aroused a significant concern among the health
      scientists globally, as diseases such as Parkinson's, Alzheimer's and dementia
      lead to disability and people have to live with them throughout the life. Recent
      evidence suggests that a number of environmental chemicals such as pesticides
      (paraquat) and metals (lead and aluminum) are also the cause of these diseases
      and other neurological disorders. Biomarkers can help in detecting the disorder
      at the preclinical stage, progression of the disease and key metabolomic
      alterations permitting identification of potential targets for intervention. A
      number of biomarkers have been proposed for some neurological disorders based on
      laboratory and clinical studies. In silico approaches have also been used by some
      investigators. Yet the ideal biomarker, which can help in early detection and
      follow-up on treatment and identifying the susceptible populations, is not
      available. An attempt has therefore been made to review the recent advancements
      of in silico approaches for discovery of biomarkers and their validation. In
      silico techniques implemented with multi-omics approaches have potential to
      provide a fast and accurate approach to identify novel biomarkers.

PMID- 29466245
TI  - Effect of the Arctic terrestrial plant Ranunculus hyperboreus on LPS-induced
      inflammatory response via MAPK pathways.
AB  - The Arctic flora hosts a limited number of species due to its extreme
      environmental conditions which also yield novel and unique secondary metabolites
      from withstanding plants. Considering a lack of research on bioactivity potential
      of Arctic flora, Ranunculus hyperboreus, an Arctic plant, was studied for its
      anti-inflammatory potential as a part of ongoing research on discovering novel
      natural bioactive products. Solvent-based fractions (H2O, n-BuOH, 85% aq. MeOH, n
      hexane) from R. hyperboreus extract were observed to decrease the elevated
      nitrate amount during the inflammatory response of lipopolysaccharide-induced
      mouse macrophage RAW264.7 cells. To some extent, treatment with fractions was
      able to regulate the expression and protein levels of inflammation-related
      enzymes, iNOS and COX-2, and pro-inflammatory cytokines, TNF-alpha, IL-1beta, and
      IL-6. The most active fractions, H2O and 85% aq. MeOH, were suggested to exert
      their effect through suppressed activation of MAPK pathways, especially JNK.
      Based on the studies of same species, phenolic glycosides were suggested to be
      the main active ingredients. To our knowledge, this is the first report of any
      bioactivity of R. hyperboreus which could be a valuable source of natural
      bioactive agents against inflammation.

PMID- 29466246
TI  - Modified aging of elite athletes revealed by analysis of epigenetic age markers.
AB  - Recent progress in epigenomics has led to the development of prediction systems
      that enable accurate age estimation from DNA methylation data. Our objective was
      to track responses to intense physical exercise of individual age-correlated DNA
      methylation markers and to infer their potential impact on the aging processes.
      The study showed accelerated DNA hypermethylation for two CpG sites in TRIM59 and
      KLF14. Both markers predicted the investigated elite athletes to be several years
      older than controls and this effect was more substantial in subjects involved in
      power sports. Accordingly, the complete 5-CpG model revealed age acceleration of
      elite athletes (P=1.503x10-7) and the result was more significant amongst power
      athletes (P=1.051x10-9). The modified methylation of TRIM59 and KLF14 in top
      athletes may be accounted for by the biological roles played by these genes.
      Their known anti-tumour and anti-inflammatory activities suggests that intense
      physical training has a complex influence on aging and potentially launches
      signalling networks that contribute to the observed lower risk of elite athletes
      to develop cardiovascular disease and cancer.

PMID- 29466247
TI  - Ultraviolet A irradiation induces senescence in human dermal fibroblasts by down
      regulating DNMT1 via ZEB1.
AB  - In this study, we report the role of DNA methyltransferase 1 (DNMT1) in
      ultraviolet A (UVA)-induced senescence in human dermal fibroblasts (HDFs). We
      show that DNMT1 expression was significantly reduced during UVA-induced
      senescence, and this senescence could be alleviated or aggravated by the up- or
      down-regulation of DNMT1, respectively. Expression of the transcription factor
      zinc finger E-box binding homeobox 1(ZEB1) also decreased after UVA irradiation,
      following a UVA-induced increase of intracellular reactive oxygen species (ROS).
      We show that ZEB1 binds to the DMNT1 promoter and regulates its transcription,
      which, in turn, affects cellular senescence. These changes in DMNT1 and ZEB1
      expression following UVA exposure were confirmed in matched skin specimens that
      had or had not been sun-exposed. On analyzing the promoter methylation of 24
      senescence associated genes in these matched skin specimens, we discovered that
      p53 promoter methylation was significantly reduced in sun-exposed skin. In vitro
      experiments confirmed that UVA irradiation reduced p53 promoter methylation, and
      DNMT1 up-regulation could reverse this effect. Collectively, down-regulation of
      ZEB1 caused by UVA induced ROS could transcriptionally inhibit DNMT1, leading to
      low methylation level of senescence related proteins p53 and increase its
      expression, eventually result in cellar senescence.

PMID- 29466248
TI  - Four common polymorphisms of BRIP1 (rs2048718, rs4988344, rs4986764, and
      rs6504074) and cancer risk: evidence from 13,716 cancer patients and 15,590
      cancer-free controls.
AB  - Previous studies have showed the associations between various BRCA1-interacting
      protein 1 (BRIP1) polymorphisms and cancer risk. But, these results were
      inconsistent. This meta-analysis based on 18 studies involving 13,716 cancer
      patients and 15,590 cancer-free controls is aimed at to evaluate the relationship
      between the four common SNPs of BRIP1 (rs2048718, rs4988344, rs4986764, and
      rs6504074) and cancer risk. The results showed a decreased risk of rs2048718 or
      rs4986764 for cervical cancer rather than breast cancer in the overall population
      (P < 0.05). However, rs6504074 was associated with gynecologic cancer risk among
      overall population (P < 0.05). Further stratification analyses by ethnicity
      indicated that all 4 polymorphisms (rs2048718, rs4988344, rs4986764, and
      rs6504074) were strongly related to cancer susceptibility in Chinese people (P <
      0.05). This meta-analysis showed that rs6504074 may play a decreased risk of
      gynecologic cancer in the overall population. Rs4988344, rs4986764, and rs6504074
      were significantly related to decreasing cancer risk in Chinese population.

PMID- 29466249
TI  - Exploiting mitochondrial targeting signal(s), TPP and bis-TPP, for eradicating
      cancer stem cells (CSCs).
AB  - Tri-phenyl-phosphonium (TPP) is a non-toxic chemical moiety that functionally
      behaves as a mitochondrial targeting signal (MTS) in living cells. Here, we
      explored the hypothesis that TPP-related compounds could be utilized to inhibit
      mitochondria in cancer stem cells (CSCs). We randomly selected 9 TPP-related
      compounds for screening, using an ATP depletion assay. Based on this approach,
      five compounds were identified as "positive hits"; two had no detectable effect
      on ATP production. Remarkably, this represents a >50% hit rate. We validated that
      the five positive hit compounds all inhibited oxygen consumption rates (OCR),
      using the Seahorse XFe96 metabolic flux analyzer. Interestingly, these TPP
      related compounds were non-toxic and had little or no effect on ATP production in
      normal human fibroblasts, but selectively targeted adherent "bulk" cancer cells.
      Finally, these positive hit compounds also inhibited the propagation of CSCs in
      suspension, as measured functionally using the 3D mammosphere assay. Therefore,
      these TPP-related compounds successfully inhibited anchorage-independent growth,
      which is normally associated with a metastatic phenotype. Interestingly, the most
      effective molecule that we identified contained two TPP moieties (i.e., bis-TPP).
      More specifically, 2-butene-1,4-bis-TPP potently and selectively inhibited CSC
      propagation, with an IC-50 < 500 nM. Thus, we conclude that the use of bis-TPP, a
      "dimeric" mitochondrial targeting signal, may be a promising new approach for the
      chemical eradication of CSCs. Future studies on the efficacy of 2-butene-1,4-bis
      TPP and its derivatives are warranted. In summary, we show that TPP-related
      compounds provide a novel chemical strategy for effectively killing both i)
      "bulk" cancer cells and ii) CSCs, while specifically minimizing or avoiding off
      target side-effects in normal cells. These results provide the necessary evidence
      that "normal" mitochondria and "malignant" mitochondria are truly biochemically
      distinct, removing a significant barrier to therapeutically targeting cancer
      metabolism.

PMID- 29466250
TI  - Evaluation of 209At as a theranostic isotope for 209At-radiopharmaceutical
      development using high-energy SPECT.
AB  - The development of alpha-emitting radiopharmaceuticals using 211At requires
      quantitative determination of the time-dependent nature of the 211At
      biodistribution. However, imaging-based methods for acquiring this information
      with 211At have not found wide-spread use because of its low abundance of decay
      emissions suitable for external detection. In this publication we demonstrate the
      theranostic abilities of the 211At/209At isotope pair and present the first-ever
      209At SPECT images. The VECTor microSPECT/PET/CT scanner was used to image 209At
      with a collimator suitable for the 511 keV annihilation photons of PET isotopes.
      Data from distinct photopeaks of the 209At energy spectrum (195 keV (22.6%), 239
      keV (12.4 %), 545 keV (91.0 %), a combined 782/790 keV peak (147 %), and 209Po x
      rays (139.0 %)) were independently evaluated for use in image reconstructions
      using Monte Carlo (GATE) simulations and phantom studies. 209At-imaging in vivo
      was demonstrated in a healthy mouse injected with 10 MBq of free [209At]astatide.
      Image-based measurements of 209At uptake in organs of interest-acquired in 5 min
      intervals-were compared to ex vivo gamma counter measurements of the same organs.
      Simulated and measured data indicated that-due to the large amount of scatter
      from high energy (>750 keV) gammas-reconstructed images using the x-ray peak
      outperformed those obtained from other peaks in terms of image uniformity and
      spatial resolution, determined to be  <0.85 mm. 209At imaging using the x-ray
      peak revealed a biodistribution that matched the known distribution of free
      astatide, and in vivo image-based measurements of 209At uptake in organs of
      interest matched ex vivo measurements within 10%. We have acquired the first
      209At SPECT images and demonstrated the ability of quantitative SPECT imaging
      with 209At to accurately determine astatine biodistributions with high spatial
      and temporal resolution.

PMID- 29466251
TI  - Kinematics and dynamics of the auto-rotation of a model winged seed.
AB  - Numerical simulations of the auto-rotation of a model winged seed are presented.
      The calculations are performed by solving simultaneously the Navier-Stokes
      equations for the flow surrounding the seed and the rigid-body equations for the
      motion of the seed. The Reynolds number based on the descent speed and a
      characteristic chord length is varied in the range 80-240. Within this range, the
      seed attains an asymptotic state with finite amplitude auto-rotation, while for
      smaller values of the Reynolds number no auto-rotation is observed. The motion of
      the seed is characterized by the coning and pitch angles, the angular velocity
      and the horizontal translation of the seed. The values obtained for these
      quantities are qualitatively similar to those reported in the literature in
      experiments with real winged seeds. When increasing the Reynolds number, the seed
      tends to rotate at higher speeds, with less inclination with respect to the
      horizontal plane, and with a larger translation velocity. With respect to the
      aerodynamic forces, it is observed that, with increasing Reynolds number, the
      horizontal components decrease in magnitude while the vertical component
      increases. The force distribution along the wing span is characterized using both
      global and local characteristic speeds and chord lengths for the non
      dimensionalisation of the force coefficients. It is found that the vertical
      component does not depend on the Reynolds number when using local scaling, while
      the chordwise component of the force does.

PMID- 29466252
TI  - INTRAVITREAL INJECTION OF PROPRANOLOL FOR THE TREATMENT OF RETINAL CAPILLARY
      HEMANGIOMA IN A CASE OF VON HIPPEL-LINDAU.
AB  - PURPOSE: The purpose of this study was to evaluate the safety and efficacy of
      intravitreal propranolol for the management of retinal capillary hemangioma in a
      patient with Von Hippel-Lindau. METHODS: Two intravitreal injections of 50
      MUg/0.05 mL propranolol were administered 6 weeks apart in the left eye of a 26
      year-old patient with bilateral multiple retinal capillary hemangiomas. Safety
      and response to therapy were evaluated using electroretinogram, fluorescein
      angiography, and measurement of visual acuity. Laser photocoagulation was
      performed in the right eye. RESULTS: One month after the second intravitreal
      injection of propranolol, fluorescein leakage decreased from the tumors located
      on the optic nerve head and in the inferonasal retinal periphery. Reduction of
      the retinal capillary hemangioma vascularity and enhancement of its fibrosis
      associated with the attenuation of the feeder vessel were also observed.
      Ophthalmic examination showed no adverse effect except for a mild transient
      vitreous haziness after each injection. Electroretinogram performed 4 weeks after
      the first injection revealed no retinal toxicity. CONCLUSION: Intravitreal
      propranolol showed a therapeutic effect on retinal capillary hemangioma with no
      short-term adverse effects except a mild transient inflammatory response in a
      patient with Von Hippel-Lindau.

PMID- 29466253
TI  - An Outpatient, Dose-Intense, Intravenous Cisplatin and Oral Etoposide Regimen for
      the Treatment of Advanced, Platinum-Resistant Ovarian Cancer.
AB  - OBJECTIVES: Advanced-stage, platinum-resistant, ovarian cancer can be treated
      with dose-intense chemotherapy; one such regimen includes intravenous cisplatin
      and oral etoposide. To minimize the toxicity associated with weekly cisplatin,
      pretreatment and posttreatment hydration is required, often necessitating
      inpatient, overnight admission. We report a shorter, within-day regimen for
      delivering weekly cisplatin. METHODS: This was a retrospective study to assess
      the use of standard (inpatient; treatment time of 12 hours) versus modified
      (outpatient; treatment time of 4 hours) regimens. The primary outcome included
      all-grade and grade 3/4 adverse events. Secondary outcomes included clinical
      benefit response and, median progression-free survival and overall survival.
      RESULTS: Between January 2012 and December 2014, 66 women with metastatic ovarian
      cancer received dose-intense weekly cisplatin and oral etoposide (n = 45
      standard, n = 21 modified). The commonest all-grade adverse events were anemia
      (96% vs 90%, standard and modified, respectively), fatigue (73% vs 67%),
      neutropenia (71% vs 76%), hypocalcemia (51% vs 43%), and thrombocytopenia (49% vs
      57%). There were no statistically significant differences in the incidence or
      grades of adverse events. The clinical benefit response was 53% in the standard
      group and 62% in the modified group (P = 0.9). The median progression-free
      survival was 4.2 and 6.5 months (incidence rate ratio, 1.22; 95% confidence
      interval, 0.71-2.15; P = 0.29), and median overall survival was 6.6 and 8.4
      months (incidence rate ratio, 1.83; 95% confidence interval, 1.04-3.35; P =
      0.03), in favor of the modified regimen. CONCLUSIONS: Our shorter, within-day
      regimen for delivering dose-intense weekly cisplatin and oral etoposide to treat
      platinum-resistant metastatic ovarian cancer is safe and efficacious.

PMID- 29466254
TI  - Characteristics and Prognosis of Stage I Ovarian Mucinous Tumors According to
      Expansile or Infiltrative Type.
AB  - BACKGROUND: The present study retrospectively determined the outcomes and
      prognoses in stage I mucinous ovarian carcinoma according to histological type
      (ie, expansile or infiltrative). METHODS: A centralized pathologic review of
      tumors in patients treated from 1976 to 2016 for ovarian mucinous carcinoma was
      performed by 2 expert pathologists according to the 2014 World Health
      Organization classification. Only patients with stage I disease were analyzed.
      Tumors were typed as expansile or infiltrative and oncological issues analyzed.
      RESULTS: A total of 114 cases were reviewed. Fifty were excluded (stage > I in 30
      cases and no accessibility to a pathological review for 20 cases). Thus, 64
      patients fulfilled the inclusion criteria: 29 had expansile-type and 35
      infiltrative-type disease. The characteristics of both groups of patients were
      comparable, except the use of nodal staging surgery, which was more frequent in
      patients with infiltrative type. The International Federation of Gynecology and
      Obstetrics stages in expansile and infiltrative types were as follows: IA in 13
      (45%) and 20 (57%), and IC in 16 (55%) and 15 (43%), respectively. Recurrence
      occurred in 3 patients with expansile type and 6 patients with infiltrative type.
      Two cases of expansile recurrence had pelvic recurrence and were salvaged after
      secondary surgery and chemotherapy, whereas 5 cases of infiltrative recurrence
      had extrapelvic spread and died from disease or were alive with progressive
      disease. CONCLUSIONS: Recurrence occurred in both types of stage I mucinous
      ovarian cancer. However, lethal recurrences were observed mainly in infiltrative
      type.

PMID- 29466255
TI  - Differential Expression of MicroRNAs in Uterine Cervical Cancer and Its
      Implications in Carcinogenesis; An Integrative Approach.
AB  - OBJECTIVES: Cervical cancer is the second most common cancer in women in
      developing countries, including India. Recently, microRNAs (miRNAs) are gaining
      importance in cancer biology because of their involvement in various cellular
      processes. The present study aimed to profile miRNA expression pattern in
      cervical cancer, identify their target genes, and understand their role in
      carcinogenesis. METHODS: Human papillomavirus (HPV) infection statuses in samples
      were assessed by heminested polymerase chain reaction followed by direct DNA
      sequencing. Next-generation sequencing and miRNA microarray were used for miRNA
      profiling in cervical cancer cell lines and tissue samples, respectively.
      MicroRNA signature was validated by quantitative real-time PCR, and biological
      significance was elucidated using various in silico analyses. RESULTS: Cervical
      cancer tissues samples were mostly infected by HPV type 16 (93%). MicroRNA
      profiling showed that the pattern of miRNA expression differed with respect to
      HPV positivity in cervical cancer cell lines. However, target and pathway
      analyses indicated identical involvement of these significantly deregulated
      miRNAs in HPV-positive cervical cancer cell lines irrespective of type of HPV
      infected. Microarray profiling identified a set of miRNAs that are differentially
      deregulated in cervical cancer tissue samples which were validated using
      quantitative real-time PCR. In silico analyses revealed that the signature miRNAs
      are mainly involved in PI3K-Akt and mTOR pathways. CONCLUSIONS: The study
      identified that high-risk HPV induces similar carcinogenic mechanism irrespective
      of HPV type. The miRNA signature of cervical cancer and their target genes were
      also elucidated, thereby providing a better insight into the molecular mechanism
      underlying cervical cancer development.

PMID- 29466256
TI  - The Impact of an Enhanced Recovery After Surgery Program on Patients Treated for
      Gynecologic Cancer in the Community Hospital Setting.
AB  - OBJECTIVES: The purpose of this study was to compare the outcomes of gynecologic
      oncology patients treated in the community hospital setting either under the
      auspices of an enhanced recovery after surgery (ERAS) protocol or in accordance
      with physician discretion. METHODS: We retrospectively evaluated a series of
      consecutive gynecologic oncology patients who were managed via open surgery in
      coincident with an ERAS pathway from January 2015 to December 2016. They were
      compared with a historical open surgery cohort who was treated from November 2013
      to December 2014. The primary clinical end points encompassed hospital length of
      stay, hospital costs, and patient readmission rates. RESULTS: There were 86
      subjects accrued in the ERAS group and 91 patients in the historical cohort. The
      implementation of ERAS occasioned a greater than 3-day mean reduction in hospital
      stay (8.04 days for the historical group vs 4.88 days for the ERAS subjects; P =
      0.001) and correspondingly diminished hospital costs ($11,877.47/patient vs
      $9305.26/patient; P = 0.04). Moreover, there were 2 readmissions (2.3%) in the
      ERAS group compared with 4 (4.4%) in the historical cohort (P = 0.282).
      CONCLUSIONS: The results from our investigation suggest that adhering to an ERAS
      protocol confers beneficial hospital length of stay and hospital cost outcomes,
      without compromising patient readmission rates. Additional investigation
      scrutinizing the impact of ERAS enactment with more defined study variables in a
      larger, randomized setting is warranted.

PMID- 29466257
TI  - Recurrent Cancer Is Associated With Dissatisfaction With Care-A Longitudinal
      Analysis Among Ovarian and Endometrial Cancer Patients.
AB  - OBJECTIVE: The primary aim of this study was to assess the longitudinal impact of
      a recurrence of gynecological cancer on satisfaction with information provision
      and care. The secondary aim was to assess the impact of a recurrence on illness
      perceptions, anxiety, and depression and health-related quality of life. METHODS:
      This study is a longitudinal analysis from the ROGY Care trial, conducted between
      2011 and 2014, including patients with endometrial (n = 215) and ovarian (n =
      149) cancer. Patients were invited to complete questionnaires directly after
      initial treatment and after 6, 12, and 24 months. Satisfaction with information
      provision and care, illness perceptions, anxiety, and depression were compared
      before and after the recurrence. Linear mixed-model analyses were conducted to
      assess the differences in outcomes of patients with a recurrence compared with
      patients without a recurrence. RESULTS: During 2-year follow-up, 25 patients with
      endometrial cancer (12%) and 64 patients with ovarian cancer (43%) had recurrent
      disease, of whom 9 endometrial and 26 ovarian cancer patients completed at least
      1 questionnaire after their recurrence was determined. Patients reported lower
      satisfaction with care after the diagnosis of a recurrence (doctor interpersonal
      skills, exchange of information between caregivers, and general satisfaction with
      care) compared with patients without recurrence. In addition, patients reported
      lower health-related quality of life, more anxiety and depression, and more
      threatening illness perceptions after diagnosis of a recurrence. CONCLUSIONS:
      After diagnosis of recurrent disease, endometrial and ovarian cancer patients
      were less satisfied with care compared with patients without a recurrence. Our
      findings suggest that patients with recurrent cancer are in need of care that is
      better tailored to their needs.

PMID- 29466258
TI  - TIME COURSE OF CHANGES IN OPTIC DISK NEOVASCULARIZATION AFTER A SINGLE
      INTRAVITREAL BEVACIZUMAB INJECTION.
AB  - PURPOSE: To evaluate the longitudinal changes in optic disk neovascularization
      (NVD) after intravitreal bevacizumab injection using optical coherence tomography
      angiography. METHODS: In this prospective, interventional, case series, eyes with
      NVD secondary to diabetic retinopathy were enrolled. En face optical coherence
      tomography angiographic images were obtained from the optic disks before and 3
      hours, 6 hours, 24 hours, 7 days, and 30 days after intravitreal bevacizumab
      injection. The size and flow area of the neovascularization were measured by two
      graders. RESULTS: Eleven eyes of 9 patients with a mean age of 52.11 +/- 9.48
      years were included. The reduction in the NVD size and flow area was
      statistically significant at 24 hours, 7 days, and 30 days after injections
      compared with the baseline measurements (all P < 0.05). The decremental
      regression in the NVD size and flow area continued during the study course. The
      changes were not statistically significant in 3-hour and 6-hour measurements (all
      P > 0.05). CONCLUSION: In this study, statistically significant regression in the
      NVD size and flow area was observed as early as 24 hours after a single
      intravitreal bevacizumab injection, with a continued decreasing trend for at
      least a 1-month period.

PMID- 29466259
TI  - An Exploration of Contributing Factors to Patient Safety.
AB  - One in 3 patients is estimated to experience health care-related harm during
      hospitalization. This descriptive, cross-sectional study used the Safety
      Attitudes Questionnaire to measure interprofessional staff perceptions of safety
      and teamwork climate and a retrospective, modified Global Trigger Tool chart
      review methodology to measure unit-level patient outcomes. Safety climate and
      teamwork did not have a statistically significant relationship with the frequency
      of adverse events identified by the Global Trigger Tool. Researchers may consider
      the Global Trigger Tool for detecting unit-level adverse events.

PMID- 29466260
TI  - Project SITUP: An Interdisciplinary Quality Improvement Initiative to Reduce
      Aspiration Pneumonia.
AB  - The purpose of this quality improvement initiative was to improve oropharyngeal
      dysphagia screening and reduce aspiration pneumonia rates on 3 inpatient hospital
      medical units. Guided by a Plan-Do-Study-Act methodology, an interdisciplinary
      health team developed and implemented a systematic process for oropharyngeal
      dysphagia screening and management. As a result, use of the screening protocol
      increased, timely initiation of speech language pathology consultations
      increased, and aspiration pneumonia rates decreased.

PMID- 29466261
TI  - Engaging Nurses in Optimizing Antimicrobial Use in ICUs: A Qualitative Study.
AB  - Antimicrobial stewardship programs (ASPs) have predominately involved infectious
      diseases physicians and pharmacists with little attention to the nurses. To
      achieve optimal success of ASPs, engagement of nurses to actively participate in
      initiatives, strategies, and solutions to combat antibiotic resistance across the
      health care spectrum is required. In this context, the experiences of local ASP
      teams engaging nurses in appropriate antimicrobial use were explored to inform
      future strategies to enhance their involvement in ASPs.

PMID- 29466262
TI  - Post-Hospital Medication Discrepancies at Home: Risk Factor for 90-Day Return to
      Emergency Department.
AB  - The purpose of this study was to evaluate the occurrence of medication
      discrepancies during transitional care home visits and the association with
      emergency department (ED) visits. Using secondary data analysis, the
      relationships between in-home medication discrepancies and 30- and 90-day ED
      utilization were examined. For every in-home medication discrepancy, the odds of
      being admitted to the ED within 90 days increased by 31%. This brief intervention
      could add a valuable component to post-hospital transition management.

PMID- 29466263
TI  - Work Intensification and Quality Assurance: Missed Nursing Care.
AB  - This article examines nurses' commentaries from a survey conducted in New Zealand
      that studied contradictions between quality assurance and work intensification in
      nursing care. Nurse managers were blamed for either avoiding or not recognizing
      work intensification affecting quality care delivery. However, the data
      illustrate key structural issues resulting in missed care that impact on patient
      safety, rather than a problem directly attributable to managers. Until these
      structural issues are addressed, missed care and adverse events will continue to
      affect the quality of care.

PMID- 29466264
TI  - Effects of High Sound Exposure During Air-Conducted Vestibular Evoked Myogenic
      Potential Testing in Children and Young Adults.
AB  - OBJECTIVES: Vestibular evoked myogenic potential (VEMP) testing is increasingly
      utilized in pediatric vestibular evaluations due to its diagnostic capability to
      identify otolith dysfunction and feasibility of testing. However, there is
      evidence demonstrating that the high-intensity stimulation level required to
      elicit a reliable VEMP response causes acoustic trauma in adults. Despite utility
      of VEMP testing in children, similar findings are unknown. It is hypothesized
      that increased sound exposure may exist in children because differences in ear
      canal volume (ECV) compared with adults, and the effect of stimulus parameters
      (e.g., signal duration and intensity) will alter exposure levels delivered to a
      child's ear. The objectives of this study are to (1) measure peak to peak
      equivalent sound pressure levels (peSPL) in children with normal hearing (CNH)
      and young adults with normal hearing (ANH) using high-intensity VEMP stimuli, (2)
      determine the effect of ECV on peSPL and calculate a safe exposure level for
      VEMP, and (3) assess whether cochlear changes exist after VEMP exposure. DESIGN:
      This was a 2-phase approach. Fifteen CNH and 12 ANH participated in phase I.
      Equivalent ECV was measured. In 1 ear, peSPL was recorded for 5 seconds at 105 to
      125 dB SPL, in 5-dB increments for 500- and 750-Hz tone bursts. Recorded peSPL
      values (accounting for stimulus duration) were then used to calculate safe sound
      energy exposure values for VEMP testing using the 132-dB recommended energy
      allowance from the 2003 European Union Guidelines. Fifteen CNH and 10 ANH
      received cervical and ocular VEMP testing in 1 ear in phase II. Subjects
      completed tympanometry, pre- and postaudiometric threshold testing, distortion
      product otoacoustic emissions, and questionnaire addressing subjective otologic
      symptoms to study the effect of VEMP exposure on cochlear function. RESULTS: (1)
      In response to high-intensity stimulation levels (e.g., 125 dB SPL), CNH had
      significantly higher peSPL measurements and smaller ECVs compared with ANH. (2) A
      significant linear relationship between equivalent ECV (as measured by diagnostic
      tympanometry) and peSPL exists and has an effect on total sound energy exposure
      level; based on data from phase I, 120 dB SPL was determined to be an
      acoustically safe stimulation level for testing in children. (3) Using calculated
      safe stimulation level for VEMP testing, there were no significant effect of VEMP
      exposure on cochlear function (as measured by audiometric thresholds, distortion
      product otoacoustic emission amplitude levels, or subjective symptoms) in CNH and
      ANH. CONCLUSIONS: peSPL sound recordings in children's ears are significantly
      higher (~3 dB) than that in adults in response to high-intensity VEMP stimuli
      that are commonly practiced. Equivalent ECV contributes to peSPL delivered to the
      ear during VEMP testing and should be considered to determine safe acoustic VEMP
      stimulus parameters; children with smaller ECVs are at risk for unsafe sound
      exposure during routine VEMP testing, and stimuli should not exceed 120 dB SPL.
      Using 120 dB SPL stimulus level for children during VEMP testing yields no change
      to cochlear function and reliable VEMP responses.

PMID- 29466266
TI  - Biomechanical Analysis of Suspension Training Push-Up.
AB  - Giancotti, GF, Fusco, A, Varalda, C, Capranica, L, and Cortis, C. Biomechanical
      analysis of suspension training push-up. J Strength Cond Res 32(3): 602-609, 2018
      The aims of this study were to evaluate the load distribution between upper and
      lower extremities during suspension training (ST) push-up at different lengths of
      ST device and to predict useful equations to estimate the training load. After
      giving informed consent for participation, 25 subjects (17 men and 8 women; age =
      28.1 +/- 5.2 years; body mass = 69.4 +/- 14.3 kg; height = 171.6 +/- 11.3 cm;
      body mass index (BMI) = 23.4 +/- 3.3 kg.m) were involved in the study. Each
      subject performed 14 static push-ups at 7 different lengths of ST device in 2
      different elbow positions. The load distribution between upper and lower
      extremities was evaluated through a load cell and a force platform, respectively.
      To evaluate body inclination, all tests were recorded and analyzed through motion
      analysis software. To estimate the training load, a multilevel model regression
      (p <= 0.05) was used. Results showed that when the length of the ST device
      increased, the body inclination decreased, whereas the ground reaction force
      decreased and the load on the ST device increased. Moreover, when subjects moved
      from extended to flexed elbow, the ground reaction force decreased and the load
      on the ST device increased. In the created regression model (intraclass
      correlation coefficient = 0.24), the reaction force was the dependent variable,
      whereas the length of the ST device, BMI, and elbow position were the independent
      variables. The main findings were that the load distribution between upper and
      lower extremities changes both when modifying the body inclination and the length
      of the straps. The use of predicted equations could help practitioners to
      personalize the workouts according to different specific aims by modifying the
      length of the ST device to guarantee load progression.

PMID- 29466265
TI  - Characteristics of Real-World Signal to Noise Ratios and Speech Listening
      Situations of Older Adults With Mild to Moderate Hearing Loss.
AB  - OBJECTIVES: The first objective was to determine the relationship between speech
      level, noise level, and signal to noise ratio (SNR), as well as the distribution
      of SNR, in real-world situations wherein older adults with hearing loss are
      listening to speech. The second objective was to develop a set of prototype
      listening situations (PLSs) that describe the speech level, noise level, SNR,
      availability of visual cues, and locations of speech and noise sources of typical
      speech listening situations experienced by these individuals. DESIGN: Twenty
      older adults with mild to moderate hearing loss carried digital recorders for 5
      to 6 weeks to record sounds for 10 hours per day. They also repeatedly completed
      in situ surveys on smartphones several times per day to report the
      characteristics of their current environments, including the locations of the
      primary talker (if they were listening to speech) and noise source (if it was
      noisy) and the availability of visual cues. For surveys where speech listening
      was indicated, the corresponding audio recording was examined. Speech-plus-noise
      and noise-only segments were extracted, and the SNR was estimated using a power
      subtraction technique. SNRs and the associated survey data were subjected to
      cluster analysis to develop PLSs. RESULTS: The speech level, noise level, and SNR
      of 894 listening situations were analyzed to address the first objective. Results
      suggested that as noise levels increased from 40 to 74 dBA, speech levels
      systematically increased from 60 to 74 dBA, and SNR decreased from 20 to 0 dB.
      Most SNRs (62.9%) of the collected recordings were between 2 and 14 dB. Very
      noisy situations that had SNRs below 0 dB comprised 7.5% of the listening
      situations. To address the second objective, recordings and survey data from 718
      observations were analyzed. Cluster analysis suggested that the participants'
      daily listening situations could be grouped into 12 clusters (i.e., 12 PLSs). The
      most frequently occurring PLSs were characterized as having the talker in front
      of the listener with visual cues available, either in quiet or in diffuse noise.
      The mean speech level of the PLSs that described quiet situations was 62.8 dBA,
      and the mean SNR of the PLSs that represented noisy environments was 7.4 dB
      (speech = 67.9 dBA). A subset of observations (n = 280), which was obtained by
      excluding the data collected from quiet environments, was further used to develop
      PLSs that represent noisier situations. From this subset, two PLSs were
      identified. These two PLSs had lower SNRs (mean = 4.2 dB), but the most frequent
      situations still involved speech from in front of the listener in diffuse noise
      with visual cues available. CONCLUSIONS: The present study indicated that visual
      cues and diffuse noise were exceedingly common in real-world speech listening
      situations, while environments with negative SNRs were relatively rare. The
      characteristics of speech level, noise level, and SNR, together with the PLS
      information reported by the present study, can be useful for researchers aiming
      to design ecologically valid assessment procedures to estimate real-world speech
      communicative functions for older adults with hearing loss.

PMID- 29466267
TI  - Effects of Sprint Interval Training With Active Recovery vs. Endurance Training
      on Aerobic and Anaerobic Power, Muscular Strength, and Sprint Ability.
AB  - Sokmen, B, Witchey, RL, Adams, GM, and Beam, WC. Effects of sprint interval
      training with active recovery vs. endurance training on aerobic and anaerobic
      power, muscular strength, and sprint ability. J Strength Cond Res 32(3): 624-631,
      2018-This study compared sprint interval training with active recovery (SITAR) to
      moderate-intensity endurance training (ET) in aerobic and anaerobic power,
      muscular strength, and sprint time results. Forty-two recreationally active
      adults were randomly assigned to a SITAR or ET group. Both groups trained 3* per
      week for 10 weeks at 75% of V[Combining Dot Above]O2max for 30 minutes weeks 1-4,
      with duration increasing to 35 minutes weeks 5-7 and 40 minutes weeks 8-10. While
      ET ran on a 400-m track without rest for the full training session, SITAR
      sprinted until the 200-m mark and recovered with fast walking or light jogging
      the second 200 m to the finish line in 3* original sprint time. Maximal oxygen
      consumption (V[Combining Dot Above]O2max), anaerobic treadmill run to exhaustion
      at 12.5 km.h at 20% incline, isokinetic leg extension and flexion strength at 60
      and 300 degrees .s, and 50 m sprint time were determined before and after
      training. Results showed a significant improvement (p <= 0.05) in absolute and
      relative V[Combining Dot Above]O2max, anaerobic treadmill run, and sprint time in
      both groups. Only SITAR showed significant improvements in isokinetic leg
      extension and flexion at 300 degrees .s and decreases in body mass (p <= 0.05).
      SITAR also showed significantly greater improvement (p <= 0.05) over ET in
      anaerobic treadmill run and 50 m sprint time. These data suggest that SITAR is a
      time-efficient strategy to induce rapid adaptations in V[Combining Dot
      Above]O2max comparable to ET with added improvements in anaerobic power,
      isokinetic strength, and sprint time not observed with ET.

PMID- 29466268
TI  - Effect of Progressive Calisthenic Push-up Training on Muscle Strength and
      Thickness.
AB  - Kotarsky, CJ, Christensen, BK, Miller, JS, and Hackney, KJ. Effect of progressive
      calisthenic push-up training on muscle strength and thickness. J Strength Cond
      Res 32(3): 651-659, 2018-Calisthenics, a form of resistance training, continue to
      increase in popularity; however, few studies have examined their effectiveness
      for muscle strength improvement. The purpose of this study was to determine
      whether progressive calisthenic push-up training (PUSH) is comparable with
      traditional bench press training (BENCH) as a technique for increasing muscle
      strength and thickness. Twenty-three healthy, moderately trained men (mean +/-
      SD: age 23 +/- 6.8 years) completed the study. Subjects were randomly assigned to
      PUSH (n = 14) and BENCH (n = 9) groups and were trained 3 days per week for 4
      weeks. Muscle thickness (MT), seated medicine ball put (MBP), 1 repetition
      maximum (1RM) bench press, and push-up progression (PUP) were measured before and
      after training. Results revealed significant increases in 1RM (p < 0.001) and PUP
      (p < 0.001) for both groups after training. The increase in PUP was significantly
      greater for PUSH (p < 0.001). No significant differences were found within groups
      for MT and MBP (p > 0.05). This study is the first to demonstrate that
      calisthenics, using different progressive variations to maintain strength
      training programming variables, can improve upper-body muscle strength.

PMID- 29466269
TI  - Neuromuscular Effects to 6 Weeks of Loaded Countermovement Jumping With
      Traditional and Daily Undulating Periodization.
AB  - Ullrich, B, Pelzer, T, and Pfeiffer, M. Neuromuscular effects to 6 weeks of
      loaded countermovement jumping with traditional and daily undulating
      periodization. J Strength Cond Res 32(3): 660-674, 2018-Loaded vertical jumps are
      routinely used to enhance athlete's power production in the lower extremity and
      to optimize jumping and sprinting performance. This study compared traditional
      (TP) and daily undulating (DUP) periodization on muscle strength, jumping
      performance, electromyographic (EMG) muscle activity, and muscle architecture
      during preseason loaded jump training. Twenty-two athletes from different team
      sports (age: 24.3 +/- 2.6 years, height: 175.9 +/- 7.5 cm, body mass: 72.2 +/-
      8.4 kg, 12 males/10 females, strength training experience: 5.1 +/- 2.2 years)
      performed 6 weeks of loaded countermovement jumping (CMJ) (18 sessions) during
      which subjects arranged the experimental training loads with either TP or DUP.
      Therefore, loading conditions corresponding to 0, 15, and 30% of individual body
      mass were used by manipulating weighted training vests and the intensity zones
      and training volume were equated between the groups. Pre- to post-training,
      center of mass (COM) maximal CMJ performance, isometric maximal voluntary
      contractive capacity of the leg extensors (MVC), EMG maximal voluntary muscle
      activity of knee extensor muscles, and vastus lateralis and rectus femoris muscle
      architecture were examined. Repeated measures multivariate analysis of variances
      (MANOVA with factors: time * training group) revealed moderate (5-16%) but
      significant (p <= 0.006) temporal increases in COM jumping height, leg extensor
      MVC and muscle architecture in both groups. Importantly, these temporal
      alterations were similar using either TP or DUP. Therefore, our data indicate
      that both periodization models can be effectively applied to increase leg
      extensor strength, vertical jumping performance, and muscle architecture during
      short-term preseason loaded jump training.

PMID- 29466270
TI  - Validity and Reliability of the Load-Velocity Relationship to Predict the One
      Repetition Maximum in Deadlift.
AB  - Ruf, L, Chery, C, Taylor, KL. Validity and reliability of the load-velocity
      relationship to predict the 1RM in deadlift. J Strength Cond Res 32(3): 681-689,
      2018-The aim of this study was to verify the reliability and validity of using
      submaximal loads from the load-velocity relationship to predict the actual 1
      repetition maximum (1RM) in the deadlift. Data from 11 resistance-trained
      athletes were analyzed performing three 1RM assessments separated by at least 3
      days. Reliability was assessed by comparing predicted 1RMs of sessions 2 and 3,
      whereas for validity purposes, predicted 1RMs of session 3 were compared with
      actual 1RMs of session 2. Mean concentric velocity at 1RM (v at 1RM) was entered
      in individualized linear regression equations, derived from the load-velocity
      relationship for 3 (20-60%, 40-80%, and 60-90% of 1RM), 4 (20-80% and 40-90% of
      1RM), and 5 (20-90% of 1RM) incremental loads to predict 1RMs. There were trivial
      changes for all predicted 1RMs between sessions with 20-90% of 1RM being the most
      reliable model. Similarly, the actual 1RM was very stable (effect size [ES] =
      0.04, 90% confidence limit [CL] [-0.03 to 0.12], typical error of measurement
      [TE] = 3.4 kg [2.5-5.4], intraclass coefficient [ICC] = 0.99 [0.96-0.996], and
      coefficient of variation [CV] = 1.9% [1.4-3.0]), whereas the v at 1RM was
      unreliable between trials (ES = -0.30, 90% CL [-0.78 to 0.17], TE = 0.029 m.s
      [0.022-0.047], ICC = 0.63 [0.19-0.86], and CV = 15.7% [11.7-26.1]). However,
      predicted 1RMs computed from all submaximal load ranges substantially
      overestimated the actual 1RM with considerable differences between athletes.
      Although 1RM predictions showed high reliability, they all overestimated the
      actual 1RM, which was stable between sessions. Therefore, it is not recommended
      to apply the prediction models used in this study to compute daily 1RMs.

PMID- 29466271
TI  - The Relationship Between Multidirectional Jumping and Performance in Change of
      Direction Tasks.
AB  - Bourgeois, FA II, Gamble, P, Gill, ND, and McGuigan, MR. The relationship between
      multidirectional jumping and performance in change of direction tasks. J Strength
      Cond Res 32(3): 690-699, 2018-This study investigated the test-retest reliability
      of 2 change of direction (COD; 180 and 45 degrees  COD) sprints and 3
      multidirectional jump (MDJ) tests. Variables examined were approach time (sprint
      before plant-step), exit time (sprint after plant-step), total time (time to
      completion) and MDJ approach time, and distance, respectively. Second, the
      ability of MDJ tests to predict performance in COD tests was examined. Twenty men
      (age: 27.5 +/- 5.9 years; height: 1.79 +/- 0.1 m; and body mass: 79.1 +/- 12.0
      kg) performed 5 trials for each assessment, executing left plant-leg (LT) and
      right plant-leg (RT) steps, on 2 testing occasions separated by 7 days. Between
      session and within-session intraclass correlation coefficients (ICCs) and
      coefficients of variation (CVs) for all measurements were calculated. Usefulness
      of COD and MDJ tests was assessed using typical error and smallest worthwhile
      change (SWC) comparison. Results showed only one MDJ measurement generated
      unstable between-session reliability. Within-session reliability of approach and
      exit COD times, and MDJ approach times possessed confidence limits (90% CL) that
      extended below 0.75 ICC. All COD total times and MDJ distances presented high
      reliability (ICC = 0.87-0.99) with low CV (0.9-4.1%). Right-leg MDJ distances
      were predictors of RT COD performances (r = 0.50-0.68, p = 0.001-0.024), whereas
      LT MDJ distances were predictors of LT180 COD performance (r = 0.67-0.71, p =
      0.001). All measurements were useful in detecting SWC in performance. These
      findings suggest the COD tests and MDJ distances are reliable for assessing and
      monitoring COD performance in similar cohorts.

PMID- 29466272
TI  - Is Vertical Jump Height an Indicator of Athletes' Power Output in Different Sport
      Modalities?
AB  - Kons, RL, Ache-Dias, J, Detanico, D, Barth, J, and Dal Pupo, J. Is vertical jump
      height an indicator of athletes' power output in different sports modalities? J
      Strength Cond Res 32(3): 708-715, 2018-This study aimed to identify whether the
      ratio standard is adequate for the scaling of peak power output (PPO) for body
      mass (BM) in athletes of different sports and to verify classification agreement
      for athletes involved in different sports using PPO scaled for BM and jump height
      (JH). One hundred and twenty-four male athletes divided into 3 different groups
      combat sports, team sports, and runners-participated in this study. Participants
      performed the countermovement jump on a force plate. Peak power output and JH
      were calculated from the vertical ground reaction force. We found different
      allometric exponents for each modality, allowing the use of the ratio standard
      for team sports. For combat sports and runners, the ratio standard was not
      considered adequate, and therefore, a specific allometric exponent for these 2
      groups was found. Significant correlations between adjusted PPO for BM (PPOADJ)
      and JH were found for all modalities, but it was higher for runners (r = 0.81)
      than team and combat sports (r = 0.63 and 0.65, respectively). Moderate agreement
      generated by the PPOADJ and JH was verified in team sports (k = 0.47) and running
      (k = 0.55) and fair agreement in combat sports (k = 0.29). We conclude that the
      ratio standard seems to be suitable only for team sports; for runners and combat
      sports, an allometric model seems adequate. The use of JH as an indicator of
      power output may be considered reasonable only for runners.

PMID- 29466273
TI  - Heart Rate Variability During Exercise: A Comparison of Artefact Correction
      Methods.
AB  - Giles, DA and Draper, N. Heart rate variability during exercise: a comparison of
      artefact correction methods. J Strength Cond Res 32(3): 726-735, 2018-There is a
      need for standard practice in the collection and processing of RR interval data
      recorded using heart rate monitors (HRMs) in research. This article assessed the
      validity of RR intervals and heart rate variability (HRV) data obtained using an
      HRM during incremental exercise and artefact correction methods. Eighteen
      participants completed an active orthostatic test and incremental running
      V[Combining Dot Above]O2max test, while simultaneous recordings using a Polar
      V800 HRM and an electrocardiogram were made. Artefacts were corrected by
      deletion; degree zero, linear, cubic, and spline interpolation; and Kubios HRV
      software. Agreement was assessed using percentage bias, effect size (ES),
      intraclass correlation coefficients (ICC), and Bland-Altman limits of agreement
      (LoA). Artefacts increased relative to exercise intensity, to a peak of 4.46%
      during 80-100% V[Combining Dot Above]O2max. Correction of RR intervals was
      necessary with unacceptably increased bias, LoA, and ES and reduced ICC in all
      but resting recordings. All correction methods resulted in data with reduced
      percentage bias and ES for resting and <60% V[Combining Dot Above]O2max
      recordings. However, at >60% V[Combining Dot Above]O2max, even with correction,
      large amounts of variation were present in HRV measures of root mean square of
      the successive difference of intervals, low-to-high frequency ratio, Poincare
      dispersion perpendicular to the axis (SD1), and sample entropy. Linear
      interpolation produced RR intervals with the lowest bias and ES. However, caution
      should be given to HRV parameters at high exercise intensities, as large amounts
      of variation were still present. Recommendations for minimizing artefacts are
      discussed, along with guidelines for their identification, correction, and
      reporting.

PMID- 29466274
TI  - Dissociated Time Course of Recovery Between Strength and Power After Isoinertial
      Resistance Loading in Rugby Union Players.
AB  - Kennedy, RA and Drake, D. Dissociated time course of recovery between strength
      and power after isoinertial resistance loading in rugby union players. J Strength
      Cond Res 32(3): 748-755, 2018-There is a substantial amount of research on the
      responses to isometric and eccentric loading. However, only a paucity of
      literature exists on the responses to isoinertial loading, especially in trained
      athletic populations using realistic loading protocols. The purpose of this study
      was to examine the acute neuromuscular response to a bout of isoinertial
      resistance loading in elite rugby players. Seventeen male (age: 19.5 +/- 2.3
      years) rugby union players performed a conventional maximal isoinertial
      resistance loading protocol. Countermovement jump (CMJ) and maximal voluntary
      isometric contraction (MVC) squat performance were measured on 3 occasions: at
      baseline, immediately post, and 48 hour post. The results indicated that the
      decrease in MVC (9.7%) is greater than or comparable with the CMJ output
      variables (4.2-10.3%), immediately postexercise. Although isometric strength had
      demonstrated a full recovery at 48 hour post, many of the key CMJ output
      variables were still impaired (p <= 0.05). Similar findings were observed in the
      normalized CMJ curves. Complete recovery of the ability to rapidly produced force
      may require more than 48 hours in many athletes. Individual responses should,
      therefore, be monitored to help plan acute and chronic training loads. It is
      recommended that future fatigue studies should incorporate temporal phase
      analyses to consider the power-, force-, velocity-, and displacement-time curves.

PMID- 29466275
TI  - Intracyclic Velocity Variation of the Center of Mass and Hip in Breaststroke
      Swimming With Maximal Intensity.
AB  - Gourgoulis, V, Koulexidis, S, Gketzenis, P, and Tzouras, G. Intra-cyclic velocity
      variation of the center of mass and hip in breaststroke swimming with maximal
      intensity. J Strength Cond Res 32(3): 830-840, 2018-The aim of the study was to
      compare the center of mass (CM) and hip (HIP) intracyclic velocity variation in
      breaststroke swimming using 3-dimensional kinematic analysis. Nine male
      breaststrokes, of moderate performance level, swam 25-m breaststroke with maximal
      intensity, and their movements were recorded, both under and above the water
      surface, using 8 digital cameras. Their CM and HIP velocities and their
      intracyclic variations were estimated after manual digitization of 28 selected
      points on the body in a complete arm and leg breaststroke cycle. Paired sample t
      tests or Wilcoxon tests, when the assumption of normality was broken, were used
      for statistical analyses. In both, CM and HIP velocity-time curves, the results
      revealed a similar pattern of 2 clear peaks associated with the leg and arm
      propulsive phases and 2 minimal velocities that corresponded to the arm and leg
      recovery phase and the lag time between the leg and arm propulsive phases,
      respectively. However, despite this similar general pattern, the HIP minimum
      resultant velocity was significantly lower, whereas its maximal value was
      significantly greater, than the corresponding CM values. Consequently, the HIP
      intracyclic swimming velocity fluctuation significantly overestimates the actual
      variation of the swimmer's velocity in breaststroke swimming.

PMID- 29466276
TI  - Changes in Energy Demand of Dance Activity and Cardiorespiratory Fitness During 1
      Year of Vocational Contemporary Dance Training.
AB  - Beck, S, Wyon, MA, and Redding, E. Changes in energy demand of dance activity and
      cardiorespiratory fitness during 1 year of vocational contemporary dance
      training. J Strength Cond Res 32(3): 841-848, 2018-Previous literature has
      demonstrated that the intensity of dance class as well as its discontinuous
      nature is not sufficient to elicit an aerobic training response and that the
      aerobic capacity of dancers is relatively low. These findings have raised
      questions on the suitability of training, through class and rehearsal, as
      adequate preparation for the physical demands of performance and a sustained,
      successful career in dance. The aim of this study was to describe changes in
      aerobic fitness and energy cost of dance movement occurring throughout 1 year of
      training. Subjects were 13 female dance students; 7 first-year undergraduate (UG)
      students, and 6 postgraduate (PG) students. At 3 time points (TP1, TP2, and TP3)
      during 1 academic year, each subject completed a treadmill test to determine
      V[Combining Dot Above]O2peak (ml.kg.min) and lactate threshold (LT) (ml.kg.min
      and %V[Combining Dot Above]O2peak) and a standardized 4-minute dance sequence,
      where the mean demand was expressed as V[Combining Dot Above]O2 (ml.kg.min),
      heart rate (b.min), %V[Combining Dot Above]O2peak, and %LT. Both groups displayed
      an overall decrease in mean V[Combining Dot Above]O2peak throughout the year,
      despite a peak in fitness at TP2 in the PG students. No significant changes in LT
      were noted over time for either group. A significant reduction in the relative
      intensity of the dance sequence, particularly in relation to mean VO2 (ml.kg.min)
      and %LT data, was observed over time in both groups, although the degree of
      change was less in the UG group than the PG group. Apparent adaptations during a
      rehearsal period in the PG group are presented in contrast to previous research
      findings. Recommendations for future research include further investigation into
      the energy demand of rehearsal and cardiorespiratory adaptation during rehearsal
      periods as well as further reporting of measures related to LT and movement
      economy.

PMID- 29466277
TI  - Optimizing a Treadmill Ramp Protocol to Evaluate Aerobic Capacity of Hemiparetic
      Poststroke Patients.
AB  - Bernardes, WL, Montenegro, RA, Monteiro, WD, de Almeida Freire, R, Massaferri, R,
      and Farinatti, P. Optimizing a treadmill ramp protocol to evaluate aerobic
      capacity of hemiparetic poststroke patients. J Strength Cond Res 32(3): 876-884,
      2018-A correct assessment of cardiopulmonary capacity is important for aerobic
      training within motor rehabilitation of poststroke hemiparetic patients (PSHPs).
      However, specific cardiopulmonary exercise testing (CPET) for these patients are
      scarce. We proposed adaptations in a protocol originally developed for PSHPs by
      Ovando et al. (CPET1). We hypothesized that our adapted protocol (CPET2) would
      improve the original test, by preventing early fatigue and increasing patients'
      peak performance. Eleven PSHPs (52 +/- 14 years, 10 men) performed both
      protocols. CPET2 integrated changes in final speed (100-120% vs. 140% maximal
      speed in 10-m walking test), treadmill inclination (final inclination of 5 vs.
      10%), and estimated test duration (10 vs. 8 minutes) to smooth the rate of
      workload increment of CPET1. Peak oxygen uptake (V[Combining Dot Above]O2peak)
      (20.3 +/- 6.1 vs. 18.6 +/- 5.0 ml.kg.min; p = 0.04), V[Combining Dot Above]O2 at
      gas exchange transition (V[Combining Dot Above]O2-GET) (11.5 +/- 2.9 vs. 9.8 +/-
      2.0 ml.kg.min; p = 0.04), and time to exhaustion (10 +/- 3 vs. 6 +/- 2 minutes; p
      < 0.001) were higher in CPET2 than in CPET1. Slopes and intercepts of regressions
      describing relationships between V[Combining Dot Above]O2 vs. workload, heart
      rate vs. workload, and V[Combining Dot Above]O2 vs. heart rate were similar
      between CPETs. However, standard errors of estimates obtained for regressions
      between heart rate vs. workload (3.0 +/- 1.3 vs. 3.8 +/- 1.0 b.min; p = 0.004)
      and V[Combining Dot Above]O2 vs. heart rate (6.0 +/- 2.1 vs. 4.8 +/- 2.4
      ml.kg.min; p = 0.05) were lower in CPET2 than in CPET1. In conclusion, the
      present adaptations in Ovando's CPET protocol increased exercise tolerance of
      PSHPs, eliciting higher V[Combining Dot Above]O2peak and V[Combining Dot Above]O2
      GET, preventing earlier fatigue, and providing better physiological relationships
      along submaximal workloads.

PMID- 29466278
TI  - Interlocking K Wires Followed by Immediate Mobilization for Fractures of the
      Hand.
AB  - We describe a technique of interlocking Kirschner wires to improve stability
      after fixation of fractures of the hand. This enables immediate mobilization of
      the injured fingers thus reducing the need for prolonged postoperative physical
      therapy and consequently diminishing chances of posttraumatic stiffness. This
      study analyzes outcomes in 83 fractures in 70 patients including 26 metacarpal
      and 57 phalangeal fractures. The technique has proven to be simple, versatile,
      and cost-effective. Patient compliance and satisfaction has been high and results
      have been gratifying.

PMID- 29466279
TI  - Examination of Behavioral, Social, and Environmental Contextual Influences on
      Sexually Transmitted Infections in At Risk, Urban, Adolescents, and Young Adults.
AB  - BACKGROUND: Despite the large body of extant literature on sexually transmitted
      infections (STIs) in adolescents and young adults (AYAs), more research on social
      and environmental contextual factors is needed. Also, further examination of STI
      indicators by gender remains a critical area of research focus. METHODS:
      Anonymous survey data were collected using audio computer-assisted self
      interviews in community venues in urban, low-income, STI prevalent, US
      neighborhoods to reach AYAs, aged 12 to 24 years. Conventional descriptive
      statistics, bivariate analysis, and multiple logistical regression models were
      used to assess indicators of a self-reported lifetime prevalence of STIs.
      RESULTS: Participants (N = 1540) were on average 20.6 years; 57.2% were women,
      the majority were racial and ethnic minorities (92%), and almost half (49.2%)
      identified as sexual minorities. Nearly one third (32.%) had 1 or more STIs. As
      expected, gender differences were identified. For AYA men, being African
      American/Black, moving residences more than 4 times since kindergarten, and
      having a history of human immunodeficiency virus testing were each positively
      associated with STIs. Also, those who strongly disagreed that many young people
      in their community exchanged sex for money had a significantly lower likelihood
      of having an STI. For AYA women, exchanging sex for drugs or money, lacking
      money, which prevented activities, and using marijuana were each associated with
      STIs. CONCLUSIONS: This research extends our understanding of social and
      environmental contextual influences on AYAs' risk for STIs. It highlights
      differences in risk exposures that are distinctly different for AYA women and
      men, suggesting the need for tailored interventions to address their unique
      economic needs and social challenges.

PMID- 29466280
TI  - Persistent injury-associated anemia and aging: Novel insights.
AB  - BACKGROUND: Hypercatecholaminemia and bone marrow dysfunction have been
      implicated in the pathophysiology of persistent injury-associated anemia. The
      elderly may be more vulnerable to bone marrow dysfunction due to high basal and
      peak catecholamine levels and impaired hematopoietic progenitor growth. We
      hypothesized that aging would adversely affect persistent injury-associated
      anemia. METHODS: Male Sprague-Dawley rats aged 8 to 9 weeks and F344-BN rats aged
      25 months were randomized to naive controls, lung contusion plus hemorrhagic
      shock (LCHS), and LCHS plus daily chronic restraint stress (LCHS/CS). Urine
      norepinephrine was measured on Days 1 and 7. Mobilization of hematopoietic
      progenitor cells (HPCs), bone marrow colony-forming units-erythroid growth, and
      peripheral blood hemoglobin, mean corpuscular volume (MCV), and red cell
      distribution width (RDW) were assessed on Day 7 (*p < 0.05 young vs. aged
      counterpart by one-way analysis of variance). RESULTS: Aged rats had higher
      norepinephrine levels at naive baseline (97* vs. 27 ng/mL) and 7 days following
      LCHS/CS when compared with young (359* vs. 127 ng/mL). Following LCHS/CS, HPC
      mobilization was greater among young rats when compared with aged (5.4 vs. 2.5%).
      Colony-forming units-erythroid growth was lower among aged animals for each group
      (naive: 47* vs. 65; LCHS: 40* vs. 50; LCHS/CS: 38* vs. 44 cells/plate). Aged
      naive rats had higher initial hemoglobin (15.2* vs. 14.3 g/dL) but lower MCV (48*
      vs. 59 fL/cell) and larger RDW at baseline and greater differences 7 days after
      LCHS/CS (MCV: 46* vs. 60 fL/cell; RDW: 17.4* vs. 16.3%). CONCLUSIONS: Compared
      with young rats, aged rats had less HPC mobilization despite elevated basal and
      peak norepinephrine. Aged rats were disproportionately affected by impaired
      hematopoietic progenitor growth and an iron-restricted red blood cell phenotype
      at baseline, which persisted 7 days after injury. Further research is needed to
      assess how the clinical approach to persistent injury-associated anemia should
      differ for elderly trauma patients.

PMID- 29466281
TI  - Managing Risk Aversion for Low-Carbon Supply Chains with Emission Abatement
      Outsourcing.
AB  - Reducing carbon emissions, including emission abatement outsourcing at the supply
      chain level, is becoming a significant but challenging problem in practice.
      Confronting this challenge, we therefore break down the practice to focus on a
      low-carbon supply chain consisting of one supplier, one manufacturer and one
      third-party emission-reducing contractor. The contractor offers a carbon
      reduction service to the manufacturer. In view of the increasing proportion of
      Greenhouse Gases (GHG) emissions and absence of carbon reduction policies in
      developing countries, we adopt the prospect of consumers' low-carbon preferences
      to capture the demand sensitivity on carbon emission. By exploiting the Mean
      Variance (MV) model, we develop a supply chain game model considering risk
      aversion. Comparing the supply chain performances of the cases under risk
      neutrality and risk aversion, we investigate the impact of the risk aversion of
      the supplier and the manufacturer on the low-carbon supply chain performances,
      respectively. We show that the risk aversion of chain members will not influence
      the relationship underlain by the profit-sharing contract between the
      manufacturer and contractor, whereas they may extend the supplier's concerning
      range. Although the manufacturer's risk aversion has a positive impact on the
      wholesale price, interestingly, the supplier's impact on the wholesale price is
      negative. Furthermore, we propose a contract to coordinate the risk-averse low
      carbon supply chain by tuning the aversion levels of the supplier and the
      manufacturer, respectively. Through numerical study, we draw on managerial
      insights for industrial practitioners to adopt a low carbon strategy potentially
      by managing the risk attitudes along the supply chain channel.

PMID- 29466282
TI  - Sea Buckthorn Pomace Supplementation in the Diet of Growing Pigs-Effects on Fatty
      Acid Metabolism, HPA Activity and Immune Status.
AB  - There is evidence that sea buckthorn, as a source of n-3 polyunsaturated fatty
      acids (n-3 PUFA), possesses health-enhancing properties and may modulate
      neuroendocrine and immune functions. In the present study, we investigated the
      effect of sea buckthorn pomace (SBP) supplementation in the diet of growing
      German Landrace pigs on fatty acids in the blood and hypothalamus, peripheral
      immune parameters and mRNA expression of corticotropin-releasing hormone (CRH),
      mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the
      hypothalamus and spleen. Pigs were fed diets supplemented with 12% of dried SBP
      or 0% SBP (control group) over an intervention period of eight weeks. The fatty
      acid profiles in blood plasma were significantly affected by SBP supplementation
      only for C18:2n-6 and n-6/n-3 PUFA ratio compared with the control group. SBP
      supplementation did not significantly affect the fatty acid concentrations in the
      hypothalamus. Furthermore, there were no significant differences in mRNA
      expression of CRH, MR and GR in the hypothalamus or of GR mRNA expression in the
      spleen. Concerning the immune status, the plasma IgG levels tended to be higher
      in SBP pigs, whereas the leukocyte distribution, mitogen-stimulated lymphocyte
      proliferation, and serum IgM levels remained unchanged. In conclusion, the SBP
      supplementation of the diet only caused moderate effects on fatty acid
      metabolism, but no significant effects on hypothalamic-pituitary-adrenal (HPA)
      activity and immunity in growing pigs. It seems that a beneficial effect of
      dietary n-3 PUFA on health and welfare is more likely to be expected during
      stressful situations.

PMID- 29466284
TI  - An Estimate of the Burden of Fungal Disease in Norway.
AB  - The aim of this study was to examine the burden of fungal disease in Norway,
      contributing to a worldwide effort to improve awareness of the needs for better
      diagnosis and treatment of such infections. We used national registers and actual
      data from the Departments of Microbiology from 2015 and estimated the incidence
      and/or prevalence of superficial, allergic and invasive fungal disease using
      published reports on specific populations at risk. One in 6 Norwegians suffered
      from fungal disease: Superficial skin infections (14.3%: 745,600) and recurrent
      vulvovaginal candidiasis in fertile women (6%: 43,123) were estimated to be the
      most frequent infections. Allergic fungal lung disease was estimated in 17,755
      patients (341/100,000). Pneumocystis jirovecii was diagnosed in 262 patients
      (5/100,000), invasive candidiasis in 400 patients (7.7/100,000), invasive
      aspergillosis in 278 patients (5.3/100,000) and mucormycosis in 7 patients
      (0.1/100,000). Particular fungal infections from certain geographic areas were
      not observed. Overall, 1.79% of the population was estimated to be affected by
      serious fungal infections in Norway in 2015. Even though estimates for invasive
      infections are small, the gravity of such infections combined with expected
      demographic changes in the future emphasizes the need for better epidemiological
      data.

PMID- 29466283
TI  - The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney
      Structure and Function in Humans: A Systematic Review.
AB  - The intrauterine environment is critical for fetal growth and organ development.
      Evidence from animal models indicates that the developing kidney is vulnerable to
      suboptimal maternal nutrition and changes in health status. However, evidence
      from human studies are yet to be synthesised. Therefore, the aim of the current
      study was to systematically review current research on the relationship between
      maternal nutrition during pregnancy and offspring kidney structure and function
      in humans. A search of five databases identified 9501 articles, of which three
      experimental and seven observational studies met the inclusion criteria.
      Nutrients reviewed to date included vitamin A (n = 3), folate and vitamin B12 (n
      = 2), iron (n = 1), vitamin D (n = 1), total energy (n = 2) and protein (n = 1).
      Seven studies were assessed as being of "positive" and three of "neutral"
      quality. A variety of populations were studied, with limited studies
      investigating maternal nutrition during pregnancy, while measurements of
      offspring kidney outcomes were diverse across studies. There was a lack of
      consistency in the timing of follow-up for offspring kidney structure and/or
      function assessments, thus limiting comparability between studies. Deficiencies
      in maternal folate, vitamin A, and total energy during pregnancy were associated
      with detrimental impacts on kidney structure and function, measured by kidney
      volume, proteinuria, eGFRcystC and mean creatinine clearance in the offspring.
      Additional experimental and longitudinal prospective studies are warranted to
      confirm this relationship, especially in Indigenous populations where the risk of
      renal disease is greater.

PMID- 29466285
TI  - The Impact of Brain Breaks Classroom-Based Physical Activities on Attitudes
      toward Physical Activity in Polish School Children in Third to Fifth Grade.
AB  - The purpose of this study was to examine the effectiveness of the Brain Breaks(r)
      Physical Activity Solutions in changing attitudes toward physical activity of
      school children in a community in Poland. In 2015, a sample of 326 pupils aged 9
      11 years old from 19 classes at three selected primary schools were randomly
      assigned to control and experimental groups within the study. During the classes,
      children in the experimental group performed physical activities two times per
      day in three to five minutes using Brain Breaks(r) videos for four months, while
      the control group did not use the videos during the test period. Students'
      attitudes toward physical activities were assessed before and after the
      intervention using the "Attitudes toward Physical Activity Scale". Repeated
      measures of ANOVA were used to examine the change from pre- to post-intervention.
      Overall, a repeated measures ANOVA indicated time-by-group interaction effects in
      'Self-efficacy on learning with video exercises', F(1.32) = 75.28, p = 0.00, eta2
      = 0.19. Although the changes are minor, there were benefits of the intervention.
      It may be concluded that HOPSports Brain Breaks(r) Physical Activity Program
      contributes to better self-efficacy on learning while using video exercise of
      primary school children.

PMID- 29466286
TI  - Free Monoterpene Isomer Profiles of Vitis Vinifera L. cv. White Wines.
AB  - Monoterpene compounds contribute floral and fruity characters to wine and are
      desired by grape growers and winemakers for many white wines. However,
      monoterpene isomers, especially monoterpene enantiomers, have been little
      explored. It is possible to identify and quantitate 17 monoterpene isomers in 148
      varietal wines from eight grape varieties; Chardonnay, Gewurztraminer, Muscat,
      Pinot gris, Riesling, Sauvignon blanc, Torrontes, and Viognier in two vintages by
      Headspace solidphase microextraction multidimensional gas chromatography mass
      spectrometry (HS-SPME-MDGC-MS). Results obtained from general linear models and
      discriminant analysis showed significant differences for the isomer profiles and
      enantiomer fractions among the eight grape varieties and four wine styles. The
      high R2 values from the fitted line show low variation in enantiomeric
      differences based on variety. These results provide an overview of the
      monoterpene isomers of wide varietal wines, and support that isomer profiles and
      enantiomer fractions could differentiate our wines by varietal and wine style.

PMID- 29466288
TI  - Research on the Transmission Characteristics of Air-Coupled Ultrasound in Double
      Layered Bonded Structures.
AB  - The ultrasonic transmission spectrum in a double-layered bonded structure is
      related closely to its interfacial stiffness. Consequently, researching the
      regularity of the transmission spectrum is of significant interest in evaluating
      the integrity of the bonded structure. Based on the spring model and the
      potential function theory, a theoretical model is developed by the transfer
      matrix method to predict the transmission spectrum in a double-layered bonded
      structure. Some shift rules of the transmission peaks are obtained by numerical
      calculation of this model with different substrates. The results show that the
      resonant transmission peaks move towards a higher frequency with the increase of
      the normal interfacial stiffness, and each of them has different movement
      distances with the increasing interfacial stiffness. Indeed, it is also observed
      that the movement starting points of these peaks are at the specific frequency at
      which the thickness of either substrate plate equals an integral multiple of half
      a wavelength. The results from measuring the bonding specimens, which have
      different interfacial properties and different substrates in this experiment, are
      utilized to verify the theoretical analysis. Though the theory of "starting
      points" is not demonstrated effectively, the shift direction and distance exactly
      match with the result from the theoretical algorithm.

PMID- 29466287
TI  - Comparison of Inhibitory Capacities of 6-, 8- and 10-Gingerols/Shogaols on the
      Canonical NLRP3 Inflammasome-Mediated IL-1beta Secretion.
AB  - Endogenous noninfectious substances that mediate the nucleotide oligomerization
      domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome
      activation and interleukin (IL)-1beta secretion causes inappropriate sterile
      inflammation and is implicated in the pathogenesis of several chronic diseases,
      such as type 2 diabetes mellitus, gout, atherosclerosis and Alzheimer's disease.
      Consequently, dietary phytochemicals exhibiting capacities to suppress canonical
      NLRP3 inflammasome-mediated IL-1beta secretion can be a reliable supplement to
      prevent such diseases. The purpose of this study was to investigate and compare
      the inhibitory effects of ginger phytochemicals, including 6-, 8- and 10
      gingerols/shogaols on the canonical NLRP3 inflammasome-mediated IL-1beta
      secretion in THP-1 macrophages with ordered stimulations of lipopolysaccharide
      (LPS) and adenosine 5'-triphosphate (ATP). At 20 MUM, the 10-gingerol and all the
      shogaols significantly inhibited canonical IL-1beta secretion. The shogaols had a
      more potent inhibitory capacity than that of corresponding gingerols. Increase of
      alkyl chain length impacted negatively the inhibitory activity of shogaols.
      Additionally, these effective ginger phytochemicals not only inhibited the LPS
      primed expression of pro-IL-1beta and NLRP3, but also decreased ATP-activated
      caspase-1. The results demonstrated that ginger phytochemicals, especially the
      most potent, 6-shogaol, might be promising for developing as an inhibitor of the
      canonical NLRP3 inflammasome-mediated IL-1beta secretion and further applied in
      prevention of NLRP3 inflammasome-associated diseases.

PMID- 29466289
TI  - Effects of Sterilization Cycles on PEEK for Medical Device Application.
AB  - The effects of the sterilization process have been studied on medical grade
      thermoplastic polyetheretherketone (PEEK). For a reusable medical device,
      material reliability is an important parameter to decide its lifetime, as it will
      be subjected to the continuous steam sterilization process. A spring nature, clip
      component was selected out of a newly designed medical device (patented) to
      perform this reliability study. This clip component was sterilized for a
      predetermined number of cycles (2, 4, 6, 8, 10, 20...100) at 121  degrees C for
      30 min. A significant decrease of ~20% in the compression force of the spring was
      observed after 30 cycles, and a ~6% decrease in the lateral dimension of the clip
      was observed after 50 cycles. No further significant change in the compression
      force or dimension was observed for the subsequent sterilization cycles. Vickers
      hardness and differential scanning calorimetry (DSC) techniques were used to
      characterize the effects of sterilization. DSC results exhibited no significant
      change in the degree of cure and melting behavior of PEEK before and after the
      sterilization. Hardness measurement exhibited an increase of ~49% in hardness
      after just 20 cycles. When an unsterilized sample was heated for repetitive
      cycles without the presence of moisture (121  degrees C, 10 and 20 cycles), only
      ~7% of the maximum change in hardness was observed.

PMID- 29466290
TI  - Different Risk Factors for Very Low Birth Weight, Term-Small-for-Gestational-Age,
      or Preterm Birth in Japan.
AB  - From 1985 to 2013, the mean birth weight of infants in Japan decreased from 3120
      g to 3000 g, and the low-birth-weight rate among live births increased from 6.3%
      to 9.6%. No prospective study has elucidated the risk factors for poor fetal
      growth and preterm birth in recent Japanese parents, such as increased parental
      age, maternal body figure, assisted reproductive technology (ART), and
      socioeconomic status. Participants were mother-infant pairs (n = 18,059) enrolled
      in a prospective birth cohort in Hokkaido, Japan from 2002 to 2013. Parental
      characteristics were obtained via self-reported questionnaires during pregnancy.
      Medical records helped identify very-low-birth-weight (VLBW; <1500g), term-small
      for-gestational-age (term-SGA), and preterm-birth (PTB; <37 weeks) infants. We
      calculated relative risks (RRs) for PTB, VLBW, and term-SGA birth based on
      parental characteristics. The prevalence of PTB, VLBW, and term-SGA was 4.5%,
      0.4%, and 6.5%, respectively. Aged parents and ART were risk factors for PTB and
      VLBW. Maternal alcohol drinking during pregnancy increased the risk; a parental
      educational level of >=16 years reduced risk of term-SGA. Maternal pre-pregnancy
      BMI of <18.5 kg/m2 increased the risk of PTB and term-SGA. The RR for low BMI was
      highest among mothers who have low educational level. Among various factors,
      appropriate nutritional education to maintain normal BMI is important to prevent
      PTB and term-SGA in Japan.

PMID- 29466291
TI  - Recommendations and Choices for BRCA Mutation Carriers at Risk for Ovarian
      Cancer: A Complicated Decision.
AB  - Current ovarian cancer screening guidelines in high-risk women vary according to
      different organizations. Risk reducing surgery remains the gold standard for
      definitive treatment in BRCA mutation carriers, but research advancements have
      created more short-term options for patients to consider. The decisions involved
      in how a woman manages her BRCA mutation status can cause a great deal of stress
      and worry due to the imperfect therapy options. The goal of this review was to
      critically analyze the screening recommendations and alternative options for high
      risk ovarian cancer patients and evaluate how these discrepancies and choices
      affect a woman's management decisions.

PMID- 29466293
TI  - Comparison of SF6 and CF4 Plasma Treatment for Surface Hydrophobization of PET
      Polymer.
AB  - The fluorination of the polymer polyethylene terephthalate in plasma created from
      SF6 or CF4 gas at various pressures was investigated. The surface was analysed by
      X-ray photoelectron spectroscopy and water contact angle measurements, whereas
      the plasma was characterized by optical emission spectroscopy. The extent of the
      polymer surface fluorination was dependent on the pressure. Up to a threshold
      pressure, the amount of fluorine on the polymer surface and the surface
      hydrophobicity were similar, which was explained by the full dissociation of the
      SF6 and CF4 gases, leading to high concentrations of fluorine radicals in the
      plasma and thus causing the saturation of the polymer surface with fluorine
      functional groups. Above the threshold pressure, the amount of fluorine on the
      polymer surface significantly decreased, whereas the oxygen concentration
      increased, leading to the formation of the hydrophilic surface. This effect,
      which was more pronounced for the SF6 plasma, was explained by the
      electronegativity of both gases.

PMID- 29466292
TI  - Targeting Leukemia Stem Cells in the Bone Marrow Niche.
AB  - Abstract: The bone marrow (BM) niche encompasses multiple cells of mesenchymal
      and hematopoietic origin and represents a unique microenvironment that is poised
      to maintain hematopoietic stem cells. In addition to its role as a primary
      lymphoid organ through the support of lymphoid development, the BM hosts various
      mature lymphoid cell types, including naive T cells, memory T cells and plasma
      cells, as well as mature myeloid elements such as monocyte/macrophages and
      neutrophils, all of which are crucially important to control leukemia initiation
      and progression. The BM niche provides an attractive milieu for tumor cell
      colonization given its ability to provide signals which accelerate tumor cell
      proliferation and facilitate tumor cell survival. Cancer stem cells (CSCs) share
      phenotypic and functional features with normal counterparts from the tissue of
      origin of the tumor and can self-renew, differentiate and initiate tumor
      formation. CSCs possess a distinct immunological profile compared with the bulk
      population of tumor cells and have evolved complex strategies to suppress immune
      responses through multiple mechanisms, including the release of soluble factors
      and the over-expression of molecules implicated in cancer immune evasion. This
      chapter discusses the latest advancements in understanding of the immunological
      BM niche and highlights current and future immunotherapeutic strategies to target
      leukemia CSCs and overcome therapeutic resistance in the clinic.

PMID- 29466294
TI  - Respiratory-gated Proton Beam Therapy for Hepatocellular Carcinoma Adjacent to
      the Gastrointestinal Tract without Fiducial Markers.
AB  - The efficacy of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) has
      been reported, but insertion of fiducial markers in the liver is usually
      required. We evaluated the efficacy and toxicity of respiratory-gated PBT without
      fiducial markers for HCC located within 2 cm of the gastrointestinal tract. From
      March 2011 to December 2015 at our institution, 40 patients were evaluated
      (median age, 72 years; range, 38-87 years). All patients underwent PBT at a dose
      of 60 to 80 cobalt gray equivalents (CGE) in 20 to 38 fractions. The median
      follow-up period was 19.9 months (range, 1.2-72.3 months). The median tumor size
      was 36.5 mm (range, 11-124 mm). Kaplan-Meier estimates of the 2-year overall
      survival, progression-free survival, and local tumor control rates were 76%, 60%,
      and 94%, respectively. One patient (2.5%) developed a grade 3 gastric ulcer and
      one (2.5%) developed grade 3 ascites retention; none of the remaining patients
      developed grade >3 toxicities (National Cancer Institute Common Terminology
      Criteria for Adverse Events ver. 4.0.). This study indicates that PBT without
      fiducial markers achieves good local control without severe treatment-related
      toxicity of the gastrointestinal tract for HCC located within 2 cm of the
      gastrointestinal tract.

PMID- 29466295
TI  - Can Plant Defence Mechanisms Provide New Approaches for the Sustainable Control
      of the Two-Spotted Spider Mite Tetranychus urticae?
AB  - Tetranychus urticae (T. urticae) Koch is a cosmopolitan, polyphagous mite which
      causes economic losses in both agricultural and ornamental plants. Some traits of
      T. urticae hamper its management, including a short life cycle, arrhenotokous
      parthenogenesis, its haplodiploid sex determination system, and its extraordinary
      ability to adapt to different hosts and environmental conditions. Currently, the
      use of chemical and biological control are the major control methods used against
      this mite. In recent years, some studies have focused on plant defence mechanisms
      against herbivores. Various families of plant compounds (such as flavonoids,
      glucosinolates, or acyl sugars) have been shown to behave as acaricides. Plants
      can be induced upon appropriate stimuli to increase their resistance against
      spider mites. This knowledge, together with the understanding of mechanisms by
      which T. urticae detoxifies and adapts to pesticides, may complement the control
      of this pest. Herein, we describe plant volatile compounds (VOCs) with repellent
      activity, and new findings about defence priming against spider mites, which
      interfere with the T. urticae performance. The use of VOCs and defence priming
      can be integrated into current management practices and reduce the damage caused
      by T. urticae in the field by implementing new, more sustainable crop management
      tools.

PMID- 29466296
TI  - Sarcoma Spheroids and Organoids-Promising Tools in the Era of Personalized
      Medicine.
AB  - Cancer treatment is rapidly evolving toward personalized medicine, which takes
      into account the individual molecular and genetic variability of tumors.
      Sophisticated new in vitro disease models, such as three-dimensional cell
      cultures, may provide a tool for genetic, epigenetic, biomedical, and
      pharmacological research, and help determine the most promising individual
      treatment. Sarcomas, malignant neoplasms originating from mesenchymal cells, may
      have a multitude of genomic aberrations that give rise to more than 70 different
      histopathological subtypes. Their low incidence and high level of
      histopathological heterogeneity have greatly limited progress in their treatment,
      and trials of clinical sarcoma are less frequent than trials of other carcinomas.
      The main advantage of 3D cultures from tumor cells or biopsy is that they provide
      patient-specific models of solid tumors, and they overcome some limitations of
      traditional 2D monolayer cultures by reflecting cell heterogeneity, native
      histologic architectures, and cell-extracellular matrix interactions. Recent
      advances promise that these models can help bridge the gap between preclinical
      and clinical research by providing a relevant in vitro model of human cancer
      useful for drug testing and studying metastatic and dormancy mechanisms. However,
      additional improvements of 3D models are expected in the future, specifically the
      inclusion of tumor vasculature and the immune system, to enhance their full
      ability to capture the biological features of native tumors in high-throughput
      screening. Here, we summarize recent advances and future perspectives of spheroid
      and organoid in vitro models of rare sarcomas that can be used to investigate
      individual molecular biology and predict clinical responses. We also highlight
      how spheroid and organoid culture models could facilitate the personalization of
      sarcoma treatment, provide specific clinical scenarios, and discuss the relative
      strengths and limitations of these models.

PMID- 29466297
TI  - A Metabolomic Approach to Predict Breast Cancer Behavior and Chemotherapy
      Response.
AB  - Although the classification of breast carcinomas into molecular or
      immunohistochemical subtypes has contributed to a better categorization of women
      into different therapeutic regimens, breast cancer nevertheless still progresses
      or recurs in a remarkable number of patients. Identifying women who would benefit
      from chemotherapy could potentially increase treatment effectiveness, which has
      important implications for long-term survival. Metabolomic analyses of fluids and
      tissues from cancer patients improve our knowledge of the reprogramming of
      metabolic pathways involved in resistance to chemotherapy. This review evaluates
      how recent metabolomic approaches have contributed to understanding the
      relationship between breast cancer and the acquisition of resistance. We focus on
      the advantages and challenges of cancer treatment and the use of new strategies
      in clinical care, which helps us comprehend drug resistance and predict responses
      to treatment.

PMID- 29466298
TI  - Expression of Lectins in Heterologous Systems.
AB  - Lectins are proteins that have the ability to recognize and bind in a reversible
      and specific way to free carbohydrates or glycoconjugates of cell membranes. For
      these reasons, they have been extensively used in a wide range of industrial and
      pharmacological applications. Currently, there is great interest in their
      production on a large scale. Unfortunately, conventional techniques do not
      provide the appropriate platform for this purpose and therefore, the heterologous
      production of lectins in different organisms has become the preferred method in
      many cases. Such systems have the advantage of providing better yields as well as
      more homogeneous and better-defined properties for the resultant products.
      However, an inappropriate choice of the expression system can cause important
      structural alterations that have repercussions on their biological activity since
      the specificity may lay in their post-translational processing, which depends
      largely on the producing organism. The present review aims to examine the most
      representative studies in the area, exposing the four most frequently used
      systems (bacteria, yeasts, plants and animal cells), with the intention of
      providing the necessary information to determine the strategy to follow in each
      case as well as their respective advantages and disadvantages.

PMID- 29466299
TI  - Further Theoretical Insight into the Mechanical Properties of Polycaprolactone
      Loaded with Organic-Inorganic Hybrid Fillers.
AB  - Experimental/theoretical analyses have already been performed on poly(epsilon
      caprolactone) (PCL) loaded with organic-inorganic fillers (PCL/TiO2 and PCL/ZrO2)
      to find a correlation between the results from the small punch test and Young's
      modulus of the materials. PCL loaded with Ti2 (PCL = 12, TiO2 = 88 wt %) and Zr2
      (PCL = 12, ZrO2 = 88 wt %) hybrid fillers showed better performances than those
      obtained for the other particle composition. In this context, the aim of current
      research is to provide further insight into the mechanical properties of PCL
      loaded with sol-gel-synthesized organic-inorganic hybrid fillers for bone tissue
      engineering. For this reason, theoretical analyses were performed by the finite
      element method. The results from the small punch test and Young's modulus of the
      materials were newly correlated. The obtained values of Young's modulus (193 MPa
      for PCL, 378 MPa for PCL/Ti2 and 415 MPa for PCL/Zr2) were higher than those
      obtained from a previous theoretical modelling (144 MPa for PCL, 282 MPa for
      PCL/Ti2 and 310 MPa for PCL/Zr2). This correlation will be an important step for
      the evaluation of Young's modulus, starting from the small punch test data.

PMID- 29466300
TI  - Active Prior Tactile Knowledge Transfer for Learning Tactual Properties of New
      Objects.
AB  - Reusing the tactile knowledge of some previously-explored objects (prior objects)
      helps us to easily recognize the tactual properties of new objects. In this
      paper, we enable a robotic arm equipped with multi-modal artificial skin, like
      humans, to actively transfer the prior tactile exploratory action experiences
      when it learns the detailed physical properties of new objects. These
      experiences, or prior tactile knowledge, are built by the feature observations
      that the robot perceives from multiple sensory modalities, when it applies the
      pressing, sliding, and static contact movements on objects with different action
      parameters. We call our method Active Prior Tactile Knowledge Transfer (APTKT),
      and systematically evaluated its performance by several experiments. Results show
      that the robot improved the discrimination accuracy by around 10 % when it used
      only one training sample with the feature observations of prior objects. By
      further incorporating the predictions from the observation models of prior
      objects as auxiliary features, our method improved the discrimination accuracy by
      over 20 % . The results also show that the proposed method is robust against
      transferring irrelevant prior tactile knowledge (negative knowledge transfer).

PMID- 29466301
TI  - Lactomycins A-C, Dephosphorylated Phoslactomycin Derivatives that Inhibit
      Cathepsin B, from the Marine-derived Streptomyces sp. ACT232.
AB  - Three new polyketides, lactomycins A (1)-C (3), were isolated from the culture
      broth of a marine-derived Streptomyces sp. ACT232 as cathepsin B inhibitors.
      Their structures were determined by a combination of NMR and MS data analyses to
      be the dephosphorylated derivatives of a phoslactomycin class of metabolites.
      Lactomycins exhibited cathepsin B inhibitory activity (IC50 0.8 to 4.5 MUg/mL).
      Even though the biosynthetic gene clusters found in the genome of the current
      strain have high similarity to those of phoslactomycin, neither phoslactomycins
      nor leustroducsins were detected by LC-MS analyses of the crude extract.

PMID- 29466302
TI  - A Hexahomotrioxacalix[3]arene-Based Ditopic Receptor for Alkylammonium Ions
      Controlled by Ag+ Ions.
AB  - A receptor cone-1 based on a hexahomotrioxacalix[3]arene bearing three pyridyl
      groups was successfully synthesized, which has a C3-symmetric conformation and is
      capable of binding alkylammonium and metal ions simultaneously in a cooperative
      fashion. It can bind alkylammonium ions through the ?-cavity formed by three aryl
      rings. This behaviour is consistent with the cone-in/cone-out conformational
      rearrangement needed to reorganize the cavity for endo-complexation. As a C3
      symmetrical pyridyl-substituted calixarene, receptor cone-1 can also bind an Ag+
      ion, and the nitrogen atoms are turned towards the inside of the cavity and
      interact with Ag+. After complexation of tris(2-pyridylamide) derivative receptor
      cone-1 with Ag+, the original C3-symmetry was retained and higher complexation
      selectivity for n-BuNH3+ versus t-BuNH3+ was observed. Thus, it is believed that
      this receptor will have a role to play in the sensing, detection, and recognition
      of Ag+ and n-BuNH3+ ions.

PMID- 29466303
TI  - Visualization of MMP-2 Activity Using Dual-Probe Nanoparticles to Detect
      Potential Metastatic Cancer Cells.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes capable
      of degrading extracellular matrix components. Previous studies have shown that
      the upregulation of MMP-2 is closely related to metastatic cancers. While Western
      blotting, zymography, and Enzyme-Linked Immunosorbent Assays (ELISA) can be used
      to measure the amount of MMP-2 activity, it is not possible to visualize the
      dynamic MMP-2 activities of cancer cells using these techniques. In this study,
      MMP-2-activated poly(lactic-co-glycolic acid) with polyethylenimine (MMP-2-PLGA
      PEI) nanoparticles were developed to visualize time-dependent MMP-2 activities.
      The MMP-2-PLGA-PEI nanoparticles contain MMP-2-activated probes that were
      detectable via fluorescence microscopy only in the presence of MMP-2 activity,
      while the Rhodamine-based probes in the nanoparticles were used to continuously
      visualize the location of the nanoparticles. This approach allowed us to
      visualize MMP-2 activities in cancer cells and their microenvironment. Our
      results showed that the MMP-2-PLGA-PEI nanoparticles were able to distinguish
      between MMP-2-positive (HaCat) and MMP-2-negative (MCF-7) cells. While the MMP-2
      PLGA-PEI nanoparticles gave fluorescent signals recovered by active recombinant
      MMP-2, there was no signal recovery in the presence of an MMP-2 inhibitor. In
      conclusion, MMP-2-PLGA-PEI nanoparticles are an effective tool to visualize
      dynamic MMP-2 activities of potential metastatic cancer cells.

PMID- 29466304
TI  - Tandem Lewis Pair Polymerization and Organocatalytic Ring-Opening Polymerization
      for Synthesizing Block and Brush Copolymers.
AB  - Lewis pair polymerization is a powerful method for preparing soluble polymers
      bearing pendant active vinyl groups by directly polymerizing dissymmetric divinyl
      polar monomers. Herein, we present a strategy for synthesizing block and brush
      copolymers via tandem Lewis pair polymerization of methacrylates, "thiol-ene"
      click reaction and organocatalytic ring-opening polymerization of lactide.

PMID- 29466305
TI  - Identification and Characterization of Phenylpropanoid Biosynthetic Genes and
      Their Accumulation in Bitter Melon (Momordica charantia).
AB  - Phenylpropanoids and flavonoids belong to a large group of secondary metabolites,
      and are considered to have antioxidant activity, which protects the cells against
      biotic and abiotic stresses. However, the accumulation of phenylpropanoids and
      flavonoids in bitter melon has rarely been studied. Here, we identify ten
      putative phenylpropanoid and flavonoid biosynthetic genes in bitter melon. Most
      genes were highly expressed in leaves and/or flowers. HPLC analysis showed that
      rutin and epicatechin were the most abundant compounds in bitter melon. Rutin
      content was the highest in leaves, whereas epicatechin was highly accumulated in
      flowers and fruits. The accumulation patterns of trans-cinnamic acid, p-coumaric
      acid, ferulic acid, kaempferol, and rutin coincide with the expression patterns
      of McPAL, McC4H, McCOMT, McFLS, and Mc3GT, respectively, suggesting that these
      genes play important roles in phenylpropanoid and flavonoid biosynthesis in
      bitter melon. In addition, we also investigated the optimum light conditions for
      enhancing phenylpropanoid and flavonoid biosynthesis and found that blue light
      was the most effective wavelength for enhanced accumulation of phenylpropanoids
      and flavonoids in bitter melon.

PMID- 29466306
TI  - Effect of the New Plant Growth Biostimulants Based on Amino Acids on Yield and
      Grain Quality of Winter Wheat.
AB  - Field and laboratory experiments were carried out in 2012-2013, aimed at
      evaluating the influence of new products stimulating plant growth based on amino
      acids on crop yield, characteristics of grain and content of macro- and
      micronutrients in winter wheat (Triticum aestivum L.). The tests included two
      formulations produced in cooperation with INTERMAG Co. (Olkusz, Poland)-AminoPrim
      and AminoHort, containing 15% and 20% amino acids, respectively, and 0.27% and
      2.1% microelements, respectively. Field experiments showed that the application
      of products based on amino acids influenced the increase of grain yield of winter
      wheat (5.4% and 11%, respectively, for the application of AminoPrim at a dose 1.0
      L/ha and AminoHort at dose 1.25 L/ha) when compared to the control group without
      biostimulant. Laboratory tests showed an increase of technological
      characteristics of grain such as ash content, Zeleny sedimentation index and
      content of protein. The use of the tested preparations at different doses also
      contributed to the increase of the nutrients content in grains, in particular
      copper (ranging 31-50%), as well as sodium (35-43%), calcium (4.3-7.9%) and
      molybdenum (3.9-16%). Biostimulants based on amino acids, tested in the present
      study, can be recommended for an efficient agricultural production.

PMID- 29466307
TI  - Distress Responses in a Routine Vaccination Context: Relationships to Early
      Childhood Mental Health.
AB  - Social and emotional competencies, such as distress regulation, are established
      in early childhood and are critical for the development of children's mental
      health and wellbeing. Routine vaccinations in primary care provide a unique
      opportunity to relate responses to a universal, relatively standardized, distress
      regulation paradigm (i.e., pain-related distress) to key developmental outcomes.
      The current study sought to examine distress regulation during routine
      vaccination in infancy and preschool as predictors of outcomes related to
      socioemotional competence in preschool. It was hypothesized that children with
      poorer distress regulation abilities post-vaccination would have lower
      socioemotional development. Furthermore, it was hypothesized that insensitive
      parenting would exacerbate this relationship for children with poor distress
      regulation abilities. As part of an ongoing longitudinal cohort, 172 parent-child
      dyads were videotaped during vaccinations in infancy and preschool, and
      subsequently participated in a full-day psychological assessment in a university
      lab. Videotapes were coded for child pre-needle distress (baseline distress),
      immediate post-needle pain-related distress reactivity (immediate distress
      reactivity), and pain-related distress regulation (distress regulation). Parent
      sensitivity during the preschool vaccination was also coded. Baseline distress
      prior to vaccination predicted greater externalizing problems and behavioral
      symptoms. Parent sensitivity did not moderate the association between any child
      distress behaviors and socioemotional development indicators. Child distress
      behaviors prior to injection, regardless of parent behavior, during the
      vaccination context may provide valuable information to health care professionals
      about child socioemotional functioning in the behavioral and emotional domains.

PMID- 29466308
TI  - The Use of Manual Vacuum Aspiration in the Treatment of Incomplete Abortions: A
      Descriptive Study from Three Public Hospitals in Malawi.
AB  - Malawi has a high maternal mortality rate, of which unsafe abortion is a major
      cause. About 140,000 induced abortions are estimated every year, despite there
      being a restrictive abortion law in place. This leads to complications, such as
      incomplete abortions, which need to be treated to avoid further harm. Although
      manual vacuum aspiration (MVA) is a safe and cheap method of evacuating the
      uterus, the most commonly used method in Malawi is curettage. Medical treatment
      is used sparingly in the country, and the Ministry of Health has been trying to
      increase the use of MVA. The aim of this study was to investigate the treatment
      of incomplete abortions in three public hospitals in Southern Malawi during a
      three-year period. All medical files from the female/gynecological wards from
      2013 to 2015 were reviewed. In total, information on obstetric history,
      demographics, and treatment were collected from 7270 women who had been treated
      for incomplete abortions. The overall use of MVA at the three hospitals during
      the study period was 11.4% (95% CI, 10.7-12.1). However, there was a major
      increase in MVA application at one District Hospital. Why there was only one
      successful hospital in this study is unclear, but may be due to more training and
      dedicated leadership at this particular hospital. Either way, the use of MVA in
      the treatment of incomplete abortions continues to be low in Malawi, despite
      recommendations from the World Health Organization (WHO) and the Malawi Ministry
      of Health.

PMID- 29466309
TI  - The Interrelationship between Family Violence, Adolescent Violence, and
      Adolescent Violent Victimization: An Application and Extension of the Cultural
      Spillover Theory in China.
AB  - The current study is the first study to emphasize family systems, violent norms,
      and violent peer association as three domains of the social environment that
      influence both adolescent violent offending and victimization among Chinese
      adolescents using a longitudinal sample. Under the framework of cultural
      spillover theory, the purpose of the current study was to explore how these three
      factors influenced adolescent violent offending and victimization. A total of
      1192 middle and high school students were randomly selected from one of the
      largest cities in Southwest China. Structural equation model analysis was applied
      to investigate the direct and indirect effect of violence in the family system on
      violent offending and victimization. The results indicated that violent offending
      and victimization overlapped among Chinese adolescents. Violent peer association
      and acceptance of the violence norm fully mediated the effect of violence in the
      family system on violent offending, and partially mediated the effect of violence
      in the family system on violent victimization. In conclusion, adolescents who had
      experienced violence in their family system were more likely to be exposed to
      violent peer influences and to accept violent norms, which increased the
      likelihood of violence perpetration and victimization later in their life.

PMID- 29466310
TI  - An Optimal Image-Based Method for Identification of Acoustic Emission (AE)
      Sources in Plate-Like Structures Using a Lead Zirconium Titanate (PZT) Sensor
      Array.
AB  - This paper proposes an innovative method for identifying the locations of
      multiple simultaneous acoustic emission (AE) events in plate-like structures from
      the view of image processing. By using a linear lead zirconium titanate (PZT)
      sensor array to record the AE wave signals, a reverse-time frequency-wavenumber
      (f-k) migration is employed to produce images displaying the locations of AE
      sources by back-propagating the AE waves. Lamb wave theory is included in the f-k
      migration to consider the dispersive property of the AE waves. Since the exact
      occurrence time of the AE events is usually unknown when recording the AE wave
      signals, a heuristic artificial bee colony (ABC) algorithm combined with an
      optimal criterion using minimum Shannon entropy is used to find the image with
      the identified AE source locations and occurrence time that mostly approximate
      the actual ones. Experimental studies on an aluminum plate with AE events
      simulated by PZT actuators are performed to validate the applicability and
      effectiveness of the proposed optimal image-based AE source identification
      method.

PMID- 29466311
TI  - mIoT Slice for 5G Systems: Design and Performance Evaluation.
AB  - Network slicing is a key feature of the upcoming 5G networks allowing the design
      and deployment of customized communication systems to integrate services provided
      by vertical industries. In this context, massive Internet of Things (mIoT) is
      regarded as a compelling use case, both for its relevance from business
      perspective, and for the technical challenges it poses to network design. With
      their envisaged massive deployment of devices requiring sporadic connectivity and
      small data transmission, yet Quality of Service (QoS) constrained, mIoT services
      will need an ad-hoc end-to-end (E2E) slice, i.e., both access and core network
      with enhanced Control and User planes (CP/UP). After revising the key
      requirements of mIoT and identifying major shortcomings of previous generation
      networks, this paper presents and evaluates an E2E mIoT network slicing solution,
      featuring a new connectivity model overcoming the load limitations of legacy
      systems. Unique in its kind, this paper addresses mIoT requirements from an end
      to-end perspective highlighting and solving, unlike most prior related work, the
      connectivity challenges posed to the core network. Results demonstrate that the
      proposed solution, reducing CP signaling and optimizing UP resource utilization,
      is a suitable candidate for next generation network standards to efficiently
      handle massive device deployment.

PMID- 29466312
TI  - Split-Ring Resonator Sensor Penetration Depth Assessment Using In Vivo Microwave
      Reflectivity and Ultrasound Measurements for Lower Extremity Trauma
      Rehabilitation.
AB  - In recent research, microwave sensors have been used to follow up the recovery of
      lower extremity trauma patients. This is done mainly by monitoring the changes of
      dielectric properties of lower limb tissues such as skin, fat, muscle, and bone.
      As part of the characterization of the microwave sensor, it is crucial to assess
      the signal penetration in in vivo tissues. This work presents a new approach for
      investigating the penetration depth of planar microwave sensors based on the
      Split-Ring Resonator in the in vivo context of the femoral area. This approach is
      based on the optimization of a 3D simulation model using the platform of CST
      Microwave Studio and consisting of a sensor of the considered type and a
      multilayered material representing the femoral area. The geometry of the layered
      material is built based on information from ultrasound images and includes mainly
      the thicknesses of skin, fat, and muscle tissues. The optimization target is the
      measured S11 parameters at the sensor connector and the fitting parameters are
      the permittivity of each layer of the material. Four positions in the femoral
      area (two at distal and two at thigh) in four volunteers are considered for the
      in vivo study. The penetration depths are finally calculated with the help of the
      electric field distribution in simulations of the optimized model for each one of
      the 16 considered positions. The numerical results show that positions at the
      thigh contribute the highest penetration values of up to 17.5 mm. This finding
      has a high significance in planning in vitro penetration depth measurements and
      other tests that are going to be performed in the future.

PMID- 29466313
TI  - Uncertainly Analysis of Two Types of Humidity Sensors by a Humidity Generator
      with a Divided-Flow System.
AB  - Humidity measurement is an important technique for the agricultural, foods,
      pharmaceuticals, and chemical industries. For the sake of convenience, electrical
      relative humidity (RH) sensors have been widely used. These sensors need to be
      calibrated to ensure their accuracy and the uncertainty measurement of these
      sensors has become a major concern. In this study, a self-made divided-flow
      generator was established to calibrate two types of electrical humidity sensors.
      The standard reference humidity was calculated from dew-point temperature and air
      dry-bulb temperature measured by a chilled mirror monitor. This divided-flow
      generator could produce consistent result of RH measurement results. The
      uncertainty of the reference standard increased with the increase of RH values.
      The combined uncertainty with the adequate calibration equations were ranged from
      0.82% to 1.45% RH for resistive humidity sensors and 0.63% to 1.4% for capacitive
      humidity sensors, respectively. This self-made, divided-flow generator, and
      calibration method are cheap, time-saving, and easy to be used. Thus, the
      proposed approach can easily be applied in research laboratories.

PMID- 29466314
TI  - Sensor Compromise Detection in Multiple-Target Tracking Systems.
AB  - Tracking multiple targets using a single estimator is a problem that is commonly
      approached within a trusted framework. There are many weaknesses that an
      adversary can exploit if it gains control over the sensors. Because the number of
      targets that the estimator has to track is not known with anticipation, an
      adversary could cause a loss of information or a degradation in the tracking
      precision. Other concerns include the introduction of false targets, which would
      result in a waste of computational and material resources, depending on the
      application. In this work, we study the problem of detecting compromised or
      faulty sensors in a multiple-target tracker, starting with the single-sensor case
      and then considering the multiple-sensor scenario. We propose an algorithm to
      detect a variety of attacks in the multiple-sensor case, via the application of
      finite set statistics (FISST), one-class classifiers and hypothesis testing using
      nonparametric techniques.

PMID- 29466315
TI  - Robust Rate Maximization for Heterogeneous Wireless Networks under Channel
      Uncertainties.
AB  - Heterogeneous wireless networks are a promising technology in next generation
      wireless communication networks, which has been shown to efficiently reduce the
      blind area of mobile communication and improve network coverage compared with the
      traditional wireless communication networks. In this paper, a robust power
      allocation problem for a two-tier heterogeneous wireless networks is formulated
      based on orthogonal frequency-division multiplexing technology. Under the
      consideration of imperfect channel state information (CSI), the robust sum-rate
      maximization problem is built while avoiding sever cross-tier interference to
      macrocell user and maintaining the minimum rate requirement of each femtocell
      user. To be practical, both of channel estimation errors from the femtocells to
      the macrocell and link uncertainties of each femtocell user are simultaneously
      considered in terms of outage probabilities of users. The optimization problem is
      analyzed under no CSI feedback with some cumulative distribution function and
      partial CSI with Gaussian distribution of channel estimation error. The robust
      optimization problem is converted into the convex optimization problem which is
      solved by using Lagrange dual theory and subgradient algorithm. Simulation
      results demonstrate the effectiveness of the proposed algorithm by the impact of
      channel uncertainties on the system performance.

PMID- 29466316
TI  - Approach for the Development of a Framework for the Identification of Activities
      of Daily Living Using Sensors in Mobile Devices.
AB  - Sensors available on mobile devices allow the automatic identification of
      Activities of Daily Living (ADL). This paper describes an approach for the
      creation of a framework for the identification of ADL, taking into account
      several concepts, including data acquisition, data processing, data fusion, and
      pattern recognition. These concepts can be mapped onto different modules of the
      framework. The proposed framework should perform the identification of ADL
      without Internet connection, performing these tasks locally on the mobile device,
      taking in account the hardware and software limitations of these devices. The
      main purpose of this paper is to present a new approach for the creation of a
      framework for the recognition of ADL, analyzing the allowed sensors available in
      the mobile devices, and the existing methods available in the literature.

PMID- 29466317
TI  - Inhibitory Effects of a Variety of Aldehydes on Amaranthus tricolor L. and
      Echinochloa crus-galli (L.) Beauv.
AB  - Thirty-seven commercial aldehydes containing aliphatic chains and aromatic rings
      as well as heteroaromatic rings were evaluated for their inhibitory activities
      against Chinese amaranth (Amaranthus tricolor L.) and barnyardgrass (Echinochloa
      crus-galli (L.) Beauv). Polysorbate 80 (Tween(r) 80) was used as a surfactant and
      the research was preliminarily conducted at 400 MUM of all aldehydes. Among these
      aldehydes, (E)-cinnamaldehyde (7) showed the greatest inhibitory effect on seed
      germination, shoot and root growth of Chinese amaranth by 54.55%, 75.53%, and
      85.13% respectively. Similarly, (E)-crotonaldehyde (5), a related alpha,beta
      unsaturated aldehyde, inhibited the germination and seedling growth of the tested
      species at a high percentage. Apart from these two unsaturated aldehydes, no
      other aliphatic aldehydes had a harmful effect on Chinese amaranth. In terms of
      benzaldehyde (6), it had no effect on the tested plant; however, many of its
      derivatives displayed some inhibitory activity. Furthermore, for the ten common
      heteroaromatic aldehydes, picolinaldehyde (32) had a high inhibitory effect on
      Chinese amaranth which closely related to the effect of (E)-crotonaldehyde (5)
      and (E)-cinnamaldehyde (7), whereas, other heteroaromatic aldehydes showed lower
      effects. In the case of a monocot plant, barnyardgrass, no tested aldehydes
      reduced seed germination, however, (E)-cinnamaldehyde (7), 2,4,6
      trimethoxybenzaldehyde (16) and 4-(dimethylamino)benzaldehyde (24) could inhibit
      the seedling growth of the plant with low to moderate levels. The herbicidal
      effects of the most active aldehydes were then further investigated in order to
      find the minimum concentration of these aldehydes suppressing the germination and
      growth of the tested plants. At concentrations as low as 50-100 MUM some
      aldehydes could inhibit the seedling growth of the tested species. The structure
      activity relationship (SAR) study reported here demonstrates the chemical clues
      governing the inhibitory activity of aldehydes which could be utilized in the
      development of highly effective herbicides in the near future.

PMID- 29466318
TI  - Biofilm Formation by the Acidophile Bacterium Acidithiobacillus thiooxidans
      Involves c-di-GMP Pathway and Pel exopolysaccharide.
AB  - Acidophile bacteria belonging to the Acidithiobacillus genus are pivotal players
      for the bioleaching of metallic values such as copper. Cell adherence to ores and
      biofilm formation, mediated by the production of extracellular polymeric
      substances, strongly favors bioleaching activity. In recent years, the second
      messenger cyclic diguanylate (c-di-GMP) has emerged as a central regulator for
      biofilm formation in bacteria. C-di-GMP pathways have been reported in different
      Acidithiobacillus species; however, c-di-GMP effectors and signal transduction
      networks are still largely uncharacterized in these extremophile species. Here we
      investigated Pel exopolysaccharide and its role in biofilm formation by sulfur
      oxidizing species Acidithiobacillusthiooxidans. We identified 39 open reading
      frames (ORFs) encoding proteins involved in c-di-GMP metabolism and signal
      transduction, including the c-di-GMP effector protein PelD, a structural
      component of the biosynthesis apparatus for Pel exopolysaccharide production. We
      found that intracellular c-di-GMP concentrations and transcription levels of pel
      genes were higher in At. thiooxidans biofilm cells compared to planktonic ones.
      By developing an At. thiooxidans DeltapelD null-mutant strain we revealed that
      Pel exopolysaccharide is involved in biofilm structure and development. Further
      studies are still necessary to understand how Pel biosynthesis is regulated in
      Acidithiobacillus species, nevertheless these results represent the first
      characterization of a c-di-GMP effector protein involved in biofilm formation by
      acidophile species.

PMID- 29466319
TI  - Skin-on-a-Chip: Transepithelial Electrical Resistance and Extracellular
      Acidification Measurements through an Automated Air-Liquid Interface.
AB  - Skin is a critical organ that plays a crucial role in defending the internal
      organs of the body. For this reason, extensive work has gone into creating
      artificial models of the epidermis for in vitro skin toxicity tests. These tissue
      models, called reconstructed human epidermis (RhE), are used by researchers in
      the pharmaceutical, cosmetic, and environmental arenas to evaluate skin toxicity
      upon exposure to xenobiotics. Here, we present a label-free solution that
      leverages the use of the intelligent mobile lab for in vitro diagnostics (IMOLA
      IVD), a noninvasive, sensor-based platform, to monitor the transepithelial
      electrical resistance (TEER) of RhE models and adherent cells cultured on porous
      membrane inserts. Murine fibroblasts cultured on polycarbonate membranes were
      first used as a test model to optimize procedures using a custom BioChip
      encapsulation design, as well as dual fluidic configurations, for continuous and
      automated perfusion of membrane-bound cultures. Extracellular acidification rate
      (EAR) and TEER of membrane-bound L929 cells were monitored. The developed
      protocol was then used to monitor the TEER of MatTek EpiDermTM RhE models over a
      period of 48 hours. TEER and EAR measurements demonstrated that the designed
      system is capable of maintaining stable cultures on the chip, monitoring
      metabolic parameters, and revealing tissue breakdown over time.

PMID- 29466320
TI  - Dynamin-Related Protein 1 at the Crossroads of Cancer.
AB  - Mitochondrial dynamics are known to have an important role in so-called age
      related diseases, including cancer. Mitochondria is an organelle involved in many
      key cellular functions and responds to physiologic or stress stimuli by adapting
      its structure and function. Perhaps the most important structural changes involve
      mitochondrial dynamics (fission and fusion), which occur in normal cells as well
      as in cells under dysregulation, such as cancer cells. Dynamin-related protein 1
      (DRP1), a member of the dynamin family of guanosine triphosphatases (GTPases), is
      the key component of mitochondrial fission machinery. Dynamin-related protein 1
      is associated with different cell processes such as apoptosis, mitochondrial
      biogenesis, mitophagy, metabolism, and cell proliferation, differentiation, and
      transformation. The role of DRP1 in tumorigenesis may seem to be paradoxical,
      since mitochondrial fission is a key mediator of two very different processes,
      cellular apoptosis and cell mitosis. Dynamin-related protein 1 has been
      associated with the development of distinct human cancers, including changes in
      mitochondrial energetics and cellular metabolism, cell proliferation, and stem
      cell maintenance, invasion, and promotion of metastases. However, the underlying
      mechanism for this association is still being explored. Herein, we review the
      published knowledge on the role of DRP1 in cancer, exploring its interaction with
      different biological processes in the tumorigenesis context.

PMID- 29466322
TI  - Environmental Temperature Controls Accumulation of Transacting siRNAs Involved in
      Heterochromatin Formation.
AB  - Genes or alleles can interact by small RNAs in a homology dependent manner
      meaning that short interfering (siRNAs) can act in trans at the chromatin level
      producing stable and heritable silencing phenotypes. Because of the puzzling data
      on endogenous paramutations, their impact contributing to adaptive evolution in a
      Lamarckian manner remains unknown. An increasing number of studies characterizes
      the underlying siRNA accumulation pathways using transgene experiments. Also in
      the ciliate Paramecium tetraurelia, we induce trans silencing on the chromatin
      level by injection of truncated transgenes. Here, we characterize the efficiency
      of this mechanism at different temperatures showing that silencing of the
      endogenous genes is temperature dependent. Analyzing different transgene
      constructs at different copy numbers, we dissected whether silencing efficiency
      is due to varying precursor RNAs or siRNA accumulation. Our data shows that
      silencing efficiency correlates with more efficient accumulation of primary
      siRNAs at higher temperatures rather than higher expression of precursor RNAs.
      Due to higher primary levels, secondary siRNAs also show temperature dependency
      and interestingly increase their relative proportion to primary siRNAs. Our data
      shows that efficient trans silencing on the chromatin level in P. tetraurelia
      depends on environmental parameters, thus being an important epigenetic factor
      limiting regulatory effects of siRNAs.

PMID- 29466321
TI  - In a quest for engineering acidophiles for biomining applications: challenges and
      opportunities.
AB  - Biomining with acidophilic microorganisms has been used at commercial scale for
      the extraction of metals from various sulfide ores. With metal demand and energy
      prices on the rise and the concurrent decline in quality and availability of
      mineral resources, there is an increasing interest in applying biomining
      technology, in particular for leaching metals from low grade minerals and wastes.
      However, bioprocessing is often hampered by the presence of inhibitory compounds
      that originate from complex ores. Synthetic biology could provide tools to
      improve the tolerance of biomining microbes to various stress factors that are
      present in biomining environments, which would ultimately increase bioleaching
      efficiency. This paper reviews the state-of-the-art tools to genetically modify
      acidophilic biomining microorganisms and the limitations of these tools. The
      first part of this review discusses resilience pathways that can be engineered in
      acidophiles to enhance their robustness and tolerance in harsh environments that
      prevail in bioleaching. The second part of the paper reviews the efforts that
      have been carried out towards engineering robust microorganisms and developing
      metabolic modelling tools. Novel synthetic biology tools have the potential to
      transform the biomining industry and facilitate the extraction of value from ores
      and wastes that cannot be processed with existing biomining microorganisms.

PMID- 29466323
TI  - Transplantation of Recombinant Vascular Endothelial Growth Factor (VEGF)189
      Neural Stem Cells Downregulates Transient Receptor Potential Vanilloid 1 (TRPV1)
      and Improves Motor Outcome in Spinal Cord Injury.
AB  - BACKGROUND Spinal cord injury (SCI) causes a rapid loss of motor neurons, leading
      to weakness and paralysis. Transplantation of neural stem cells is known to
      restore the neuronal activity but is inefficient due to limited regenerative
      capability and low rate of survival. There has been an emphasis on the use of
      growth factors along with neural stem cells (NSCs) to enhance the neuronal
      recovery. Transplantation of recombinant NSCs with vascular endothelial growth
      factor (VEGF) might promote neuronal repair. This effect might be attributed to
      the reduced transient receptor potential vanilloid 1 (TRPV1) expression following
      transplantation. MATERIAL AND METHODS NSCs were cultured from the embryos of
      Sprague-Dawley rats (E12.5). Four group of rats (n=10, each) were subjected to
      SCI and allowed to recover for 1 week. Recombinant VEGF-NSCs, normal NSCs and PBS
      were intrathecally administered to the rats. VEGF and TRPV-1 expression at mRNA
      and protein level was evaluated. ELISA was performed to determine the release of
      neurotrophic factors after the transplantation. Motor neurons and axons were
      counted and the motor behavioral outcome was assessed using the rota-rod test.
      RESULTS VEGF-NSC transgene transplantation resulted in an enhanced neuronal
      repair and motor behavioral outcome compared to the normal NSCs transplanted
      group. VEGF-NSCs increased the release of neurotrophic factors and reduced the
      expression of TRPV1. CONCLUSIONS Recombinant VEGF-NSCs transplantation following
      SCI is more efficacious compared to normal NSC transplantation. This might also
      be related to a reduced pain in the process of recovery due to reduced TRPV1
      expression.

PMID- 29466324
TI  - Sequences enriched in Alu repeats drive nuclear localization of long RNAs in
      human cells.
AB  - Long noncoding RNAs (lncRNAs) are emerging as key parts of multiple cellular
      pathways, but their modes of action and how these are dictated by sequence remain
      unclear. lncRNAs tend to be enriched in the nuclear fraction, whereas most mRNAs
      are overtly cytoplasmic, although several studies have found that hundreds of
      mRNAs in various cell types are retained in the nucleus. It is thus conceivable
      that some mechanisms that promote nuclear enrichment are shared between lncRNAs
      and mRNAs. Here, to identify elements in lncRNAs and mRNAs that can force nuclear
      localization, we screened libraries of short fragments tiled across nuclear RNAs,
      which were cloned into the untranslated regions of an efficiently exported mRNA.
      The screen identified a short sequence derived from Alu elements and bound by
      HNRNPK that increased nuclear accumulation. Binding of HNRNPK to C-rich motifs
      outside Alu elements is also associated with nuclear enrichment in both lncRNAs
      and mRNAs, and this mechanism is conserved across species. Our results thus
      identify a pathway for regulation of RNA accumulation and subcellular
      localization that has been co-opted to regulate the fate of transcripts with
      integrated Alu elements.

PMID- 29466325
TI  - Electromechanical vortex filaments during cardiac fibrillation.
AB  - The self-organized dynamics of vortex-like rotating waves, which are also known
      as scroll waves, are the basis of the formation of complex spatiotemporal
      patterns in many excitable chemical and biological systems. In the heart,
      filament-like phase singularities that are associated with three-dimensional
      scroll waves are considered to be the organizing centres of life-threatening
      cardiac arrhythmias. The mechanisms that underlie the onset, maintenance and
      control of electromechanical turbulence in the heart are inherently three
      dimensional phenomena. However, it has not previously been possible to visualize
      the three-dimensional spatiotemporal dynamics of scroll waves inside cardiac
      tissues. Here we show that three-dimensional mechanical scroll waves and filament
      like phase singularities can be observed deep inside the contracting heart wall
      using high-resolution four-dimensional ultrasound-based strain imaging. We found
      that mechanical phase singularities co-exist with electrical phase singularities
      during cardiac fibrillation. We investigated the dynamics of electrical and
      mechanical phase singularities by simultaneously measuring the membrane
      potential, intracellular calcium concentration and mechanical contractions of the
      heart. We show that cardiac fibrillation can be characterized using the three
      dimensional spatiotemporal dynamics of mechanical phase singularities, which
      arise inside the fibrillating contracting ventricular wall. We demonstrate that
      electrical and mechanical phase singularities show complex interactions and we
      characterize their dynamics in terms of trajectories, topological charge and
      lifetime. We anticipate that our findings will provide novel perspectives for non
      invasive diagnostic imaging and therapeutic applications.

PMID- 29466326
TI  - Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug
      risperidone.
AB  - Dopamine is a neurotransmitter that has been implicated in processes as diverse
      as reward, addiction, control of coordinated movement, metabolism and hormonal
      secretion. Correspondingly, dysregulation of the dopaminergic system has been
      implicated in diseases such as schizophrenia, Parkinson's disease, depression,
      attention deficit hyperactivity disorder, and nausea and vomiting. The actions of
      dopamine are mediated by a family of five G-protein-coupled receptors. The D2
      dopamine receptor (DRD2) is the primary target for both typical and atypical
      antipsychotic drugs, and for drugs used to treat Parkinson's disease.
      Unfortunately, many drugs that target DRD2 cause serious and potentially life
      threatening side effects due to promiscuous activities against related receptors.
      Accordingly, a molecular understanding of the structure and function of DRD2
      could provide a template for the design of safer and more effective medications.
      Here we report the crystal structure of DRD2 in complex with the widely
      prescribed atypical antipsychotic drug risperidone. The DRD2-risperidone
      structure reveals an unexpected mode of antipsychotic drug binding to dopamine
      receptors, and highlights structural determinants that are essential for the
      actions of risperidone and related drugs at DRD2.

PMID- 29466328
TI  - Probing the interatomic potential of solids with strong-field nonlinear
      phononics.
AB  - Nonlinear optical techniques at visible frequencies have long been applied to
      condensed matter spectroscopy. However, because many important excitations of
      solids are found at low energies, much can be gained from the extension of
      nonlinear optics to mid-infrared and terahertz frequencies. For example, the
      nonlinear excitation of lattice vibrations has enabled the dynamic control of
      material functions. So far it has only been possible to exploit second-order
      phonon nonlinearities at terahertz field strengths near one million volts per
      centimetre. Here we achieve an order-of-magnitude increase in field strength and
      explore higher-order phonon nonlinearities. We excite up to five harmonics of the
      A1 (transverse optical) phonon mode in the ferroelectric material lithium
      niobate. By using ultrashort mid-infrared laser pulses to drive the atoms far
      from their equilibrium positions, and measuring the large-amplitude atomic
      trajectories, we can sample the interatomic potential of lithium niobate,
      providing a benchmark for ab initio calculations for the material. Tomography of
      the energy surface by high-order nonlinear phononics could benefit many aspects
      of materials research, including the study of classical and quantum phase
      transitions.

PMID- 29466327
TI  - The atomic structure of a eukaryotic oligosaccharyltransferase complex.
AB  - N-glycosylation is a ubiquitous modification of eukaryotic secretory and membrane
      bound proteins; about 90% of glycoproteins are N-glycosylated. The reaction is
      catalysed by an eight-protein oligosaccharyltransferase (OST) complex that is
      embedded in the endoplasmic reticulum membrane. Our understanding of eukaryotic
      protein N-glycosylation has been limited owing to the lack of high-resolution
      structures. Here we report a 3.5 A resolution cryo-electron microscopy structure
      of the Saccharomyces cerevisiae OST complex, revealing the structures of subunits
      Ost1-Ost5, Stt3, Wbp1 and Swp1. We found that seven phospholipids mediate many of
      the inter-subunit interactions, and an Stt3 N-glycan mediates interactions with
      Wbp1 and Swp1 in the lumen. Ost3 was found to mediate the OST-Sec61 translocon
      interface, funnelling the acceptor peptide towards the OST catalytic site as the
      nascent peptide emerges from the translocon. The structure provides insights into
      co-translational protein N-glycosylation, and may facilitate the development of
      small-molecule inhibitors that target this process.

PMID- 29466329
TI  - Circadian clock neurons constantly monitor environmental temperature to set sleep
      timing.
AB  - Circadian clocks coordinate behaviour, physiology and metabolism with Earth's
      diurnal cycle. These clocks entrain to both light and temperature cycles, and
      daily environmental temperature oscillations probably contribute to human sleep
      patterns. However, the neural mechanisms through which circadian clocks monitor
      environmental temperature and modulate behaviour remain poorly understood. Here
      we elucidate how the circadian clock neuron network of Drosophila melanogaster
      processes changes in environmental temperature. In vivo calcium-imaging
      techniques demonstrate that the posterior dorsal neurons 1 (DN1ps), which are a
      discrete subset of sleep-promoting clock neurons, constantly monitor modest
      changes in environmental temperature. We find that these neurons are acutely
      inhibited by heating and excited by cooling; this is an unexpected result when
      considering the strong correlation between temperature and light, and the fact
      that light excites clock neurons. We demonstrate that the DN1ps rely on
      peripheral thermoreceptors located in the chordotonal organs and the aristae. We
      also show that the DN1ps and their thermosensory inputs are required for the
      normal timing of sleep in the presence of naturalistic temperature cycles. These
      results identify the DN1ps as a major gateway for temperature sensation into the
      circadian neural network, which continuously integrates temperature changes to
      coordinate the timing of sleep and activity.

PMID- 29466331
TI  - Evolutionary history resolves global organization of root functional traits.
AB  - Plant roots have greatly diversified in form and function since the emergence of
      the first land plants, but the global organization of functional traits in roots
      remains poorly understood. Here we analyse a global dataset of 10 functionally
      important root traits in metabolically active first-order roots, collected from
      369 species distributed across the natural plant communities of 7 biomes. Our
      results identify a high degree of organization of root traits across species and
      biomes, and reveal a pattern that differs from expectations based on previous
      studies of leaf traits. Root diameter exerts the strongest influence on root
      trait variation across plant species, growth forms and biomes. Our analysis
      suggests that plants have evolved thinner roots since they first emerged in land
      ecosystems, which has enabled them to markedly improve their efficiency of soil
      exploration per unit of carbon invested and to reduce their dependence on
      symbiotic mycorrhizal fungi. We also found that diversity in root morphological
      traits is greatest in the tropics, where plant diversity is highest and many
      ancestral phylogenetic groups are preserved. Diversity in root morphology
      declines sharply across the sequence of tropical, temperate and desert biomes,
      presumably owing to changes in resource supply caused by seasonally inhospitable
      abiotic conditions. Our results suggest that root traits have evolved along a
      spectrum bounded by two contrasting strategies of root life: an ancestral
      'conservative' strategy in which plants with thick roots depend on symbiosis with
      mycorrhizal fungi for soil resources and a more-derived 'opportunistic' strategy
      in which thin roots enable plants to more efficiently leverage photosynthetic
      carbon for soil exploration. These findings imply that innovations of belowground
      traits have had an important role in preparing plants to colonize new habitats,
      and in generating biodiversity within and across biomes.

PMID- 29466332
TI  - Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs
      complex.
AB  - The class B glucagon-like peptide-1 (GLP-1) G protein-coupled receptor is a major
      target for the treatment of type 2 diabetes and obesity. Endogenous and mimetic
      GLP-1 peptides exhibit biased agonism-a difference in functional selectivity-that
      may provide improved therapeutic outcomes. Here we describe the structure of the
      human GLP-1 receptor in complex with the G protein-biased peptide exendin-P5 and
      a Galphas heterotrimer, determined at a global resolution of 3.3 A. At the
      extracellular surface, the organization of extracellular loop 3 and proximal
      transmembrane segments differs between our exendin-P5-bound structure and
      previous GLP-1-bound GLP-1 receptor structure. At the intracellular face, there
      was a six-degree difference in the angle of the Galphas-alpha5 helix engagement
      between structures, which was propagated across the G protein heterotrimer. In
      addition, the structures differed in the rate and extent of conformational
      reorganization of the Galphas protein. Our structure provides insights into the
      molecular basis of biased agonism.

PMID- 29466330
TI  - The genomic history of southeastern Europe.
AB  - Farming was first introduced to Europe in the mid-seventh millennium bc, and was
      associated with migrants from Anatolia who settled in the southeast before
      spreading throughout Europe. Here, to understand the dynamics of this process, we
      analysed genome-wide ancient DNA data from 225 individuals who lived in
      southeastern Europe and surrounding regions between 12000 and 500 bc. We document
      a west-east cline of ancestry in indigenous hunter-gatherers and, in eastern
      Europe, the early stages in the formation of Bronze Age steppe ancestry. We show
      that the first farmers of northern and western Europe dispersed through
      southeastern Europe with limited hunter-gatherer admixture, but that some early
      groups in the southeast mixed extensively with hunter-gatherers without the sex
      biased admixture that prevailed later in the north and west. We also show that
      southeastern Europe continued to be a nexus between east and west after the
      arrival of farmers, with intermittent genetic contact with steppe populations
      occurring up to 2,000 years earlier than the migrations from the steppe that
      ultimately replaced much of the population of northern Europe.

PMID- 29466333
TI  - The cryo-electron microscopy structure of huntingtin.
AB  - Huntingtin (HTT) is a large (348 kDa) protein that is essential for embryonic
      development and is involved in diverse cellular activities such as vesicular
      transport, endocytosis, autophagy and the regulation of transcription. Although
      an integrative understanding of the biological functions of HTT is lacking, the
      large number of identified HTT interactors suggests that it serves as a protein
      protein interaction hub. Furthermore, Huntington's disease is caused by a
      mutation in the HTT gene, resulting in a pathogenic expansion of a polyglutamine
      repeat at the amino terminus of HTT. However, only limited structural information
      regarding HTT is currently available. Here we use cryo-electron microscopy to
      determine the structure of full-length human HTT in a complex with HTT-associated
      protein 40 (HAP40; encoded by three F8A genes in humans) to an overall resolution
      of 4 A. HTT is largely alpha-helical and consists of three major domains. The
      amino- and carboxy-terminal domains contain multiple HEAT (huntingtin, elongation
      factor 3, protein phosphatase 2A and lipid kinase TOR) repeats arranged in a
      solenoid fashion. These domains are connected by a smaller bridge domain
      containing different types of tandem repeats. HAP40 is also largely alpha-helical
      and has a tetratricopeptide repeat-like organization. HAP40 binds in a cleft and
      contacts the three HTT domains by hydrophobic and electrostatic interactions,
      thereby stabilizing the conformation of HTT. These data rationalize previous
      biochemical results and pave the way for improved understanding of the diverse
      cellular functions of HTT.

PMID- 29466334
TI  - Skin electronics from scalable fabrication of an intrinsically stretchable
      transistor array.
AB  - Skin-like electronics that can adhere seamlessly to human skin or within the body
      are highly desirable for applications such as health monitoring, medical
      treatment, medical implants and biological studies, and for technologies that
      include human-machine interfaces, soft robotics and augmented reality. Rendering
      such electronics soft and stretchable-like human skin-would make them more
      comfortable to wear, and, through increased contact area, would greatly enhance
      the fidelity of signals acquired from the skin. Structural engineering of rigid
      inorganic and organic devices has enabled circuit-level stretchability, but this
      requires sophisticated fabrication techniques and usually suffers from reduced
      densities of devices within an array. We reasoned that the desired parameters,
      such as higher mechanical deformability and robustness, improved skin
      compatibility and higher device density, could be provided by using intrinsically
      stretchable polymer materials instead. However, the production of intrinsically
      stretchable materials and devices is still largely in its infancy: such materials
      have been reported, but functional, intrinsically stretchable electronics have
      yet to be demonstrated owing to the lack of a scalable fabrication technology.
      Here we describe a fabrication process that enables high yield and uniformity
      from a variety of intrinsically stretchable electronic polymers. We demonstrate
      an intrinsically stretchable polymer transistor array with an unprecedented
      device density of 347 transistors per square centimetre. The transistors have an
      average charge-carrier mobility comparable to that of amorphous silicon, varying
      only slightly (within one order of magnitude) when subjected to 100 per cent
      strain for 1,000 cycles, without current-voltage hysteresis. Our transistor
      arrays thus constitute intrinsically stretchable skin electronics, and include an
      active matrix for sensory arrays, as well as analogue and digital circuit
      elements. Our process offers a general platform for incorporating other
      intrinsically stretchable polymer materials, enabling the fabrication of next
      generation stretchable skin electronic devices.

PMID- 29466335
TI  - Global elevational diversity and diversification of birds.
AB  - Mountain ranges harbour exceptionally high biodiversity, which is now under
      threat from rapid environmental change. However, despite decades of effort, the
      limited availability of data and analytical tools has prevented a robust and
      truly global characterization of elevational biodiversity gradients and their
      evolutionary origins. This has hampered a general understanding of the processes
      involved in the assembly and maintenance of montane communities. Here we show
      that a worldwide mid-elevation peak in bird richness is driven by wide-ranging
      species and disappears when we use a subsampling procedure that ensures even
      species representation in space and facilitates evolutionary interpretation.
      Instead, richness corrected for range size declines linearly with increasing
      elevation. We find that the more depauperate assemblages at higher elevations are
      characterized by higher rates of diversification across all mountain regions,
      rejecting the idea that lower recent diversification rates are the general cause
      of less diverse biota. Across all elevations, assemblages on mountains with high
      rates of past temperature change exhibit more rapid diversification, highlighting
      the importance of climatic fluctuations in driving the evolutionary dynamics of
      mountain biodiversity. While different geomorphological and climatic attributes
      of mountain regions have been pivotal in determining the remarkable richness
      gradients observed today, our results underscore the role of ongoing and often
      very recent diversification processes in maintaining the unique and highly
      adapted biodiversity of higher elevations.

PMID- 29466336
TI  - Population snapshots predict early haematopoietic and erythroid hierarchies.
AB  - The formation of red blood cells begins with the differentiation of multipotent
      haematopoietic progenitors. Reconstructing the steps of this differentiation
      represents a general challenge in stem-cell biology. Here we used single-cell
      transcriptomics, fate assays and a theory that allows the prediction of cell
      fates from population snapshots to demonstrate that mouse haematopoietic
      progenitors differentiate through a continuous, hierarchical structure into seven
      blood lineages. We uncovered coupling between the erythroid and the basophil or
      mast cell fates, a global haematopoietic response to erythroid stress and novel
      growth factor receptors that regulate erythropoiesis. We defined a flow cytometry
      sorting strategy to purify early stages of erythroid differentiation, completely
      isolating classically defined burst-forming and colony-forming progenitors. We
      also found that the cell cycle is progressively remodelled during erythroid
      development and during a sharp transcriptional switch that ends the colony
      forming progenitor stage and activates terminal differentiation. Our work
      showcases the utility of linking transcriptomic data to predictive fate models,
      and provides insights into lineage development in vivo.

PMID- 29466340
TI  - Corrigendum: Rare cell variability and drug-induced reprogramming as a mode of
      cancer drug resistance.
AB  - This corrects the article DOI: 10.1038/nature22794.

PMID- 29466339
TI  - Intragenic origins due to short G1 phases underlie oncogene-induced DNA
      replication stress.
AB  - Oncogene-induced DNA replication stress contributes critically to the genomic
      instability that is present in cancer. However, elucidating how oncogenes
      deregulate DNA replication has been impeded by difficulty in mapping replication
      initiation sites on the human genome. Here, using a sensitive assay to monitor
      nascent DNA synthesis in early S phase, we identified thousands of replication
      initiation sites in cells before and after induction of the oncogenes CCNE1 and
      MYC. Remarkably, both oncogenes induced firing of a novel set of DNA replication
      origins that mapped within highly transcribed genes. These ectopic origins were
      normally suppressed by transcription during G1, but precocious entry into S
      phase, before all genic regions had been transcribed, allowed firing of origins
      within genes in cells with activated oncogenes. Forks from oncogene-induced
      origins were prone to collapse, as a result of conflicts between replication and
      transcription, and were associated with DNA double-stranded break formation and
      chromosomal rearrangement breakpoints both in our experimental system and in a
      large cohort of human cancers. Thus, firing of intragenic origins caused by
      premature S phase entry represents a mechanism of oncogene-induced DNA
      replication stress that is relevant for genomic instability in human cancer.

PMID- 29466338
TI  - Extreme disorder in an ultrahigh-affinity protein complex.
AB  - Molecular communication in biology is mediated by protein interactions. According
      to the current paradigm, the specificity and affinity required for these
      interactions are encoded in the precise complementarity of binding interfaces.
      Even proteins that are disordered under physiological conditions or that contain
      large unstructured regions commonly interact with well-structured binding sites
      on other biomolecules. Here we demonstrate the existence of an unexpected
      interaction mechanism: the two intrinsically disordered human proteins histone H1
      and its nuclear chaperone prothymosin-alpha associate in a complex with picomolar
      affinity, but fully retain their structural disorder, long-range flexibility and
      highly dynamic character. On the basis of closely integrated experiments and
      molecular simulations, we show that the interaction can be explained by the large
      opposite net charge of the two proteins, without requiring defined binding sites
      or interactions between specific individual residues. Proteome-wide sequence
      analysis suggests that this interaction mechanism may be abundant in eukaryotes.

PMID- 29466341
TI  - Coming of Age With Cancer: Physical, Social, and Financial Barriers to
      Independence Among Emerging Adult Survivors
AB  - PURPOSE: To explore the transition to self-care among a sample of emerging adult
      cancer survivors after hematopoietic cell transplantation (HCT). ?. PARTICIPANTS
      &AMP; SETTING: 18 HCT survivors who were aged 18-29 years at the time of HCT for
      a primary hematologic malignancy and were 8-60 months post-HCT participated in
      the study. The study took place in the hematology outpatient setting at City of
      Hope National Medical Center.?. METHODOLOGIC APPROACH: The authors conducted in
      depth semistructured interviews and analyzed interview transcripts using grounded
      theory methodology.?. FINDINGS: Health-related setbacks following HCT disrupted
      not only participants' journey toward self-care, but also their overarching
      developmental trajectory toward adulthood. Physically, participants struggled
      with lack of personal space around caregivers, but felt unready to live on their
      own. Socially, they relied on multiple caregivers to avoid relying too much on
      any one person. Financially, participants worried about prolonged dependence and
      increased needs in the future.?. IMPLICATIONS FOR NURSING: Nurses can support the
      transition to self-care among emerging adults after HCT by recognizing the
      broader developmental impact of their cancer experience.

PMID- 29466342
TI  - Early Identification of Intracranial Hemorrhage Using a Predictive Nomogram
AB  - OBJECTIVES: To identify predictive signs and symptoms occurring in hospitalized
      adults with hematologic malignancies with intracranial hemorrhage (IH).?. SAMPLE
      &AMP; SETTING: In a National Cancer Institute (NCI)-designated comprehensive
      cancer center, a retrospective matched case-control design included adult
      inpatients with hematologic malignancies with (n = 39) and without (n = 39) IH.?.
      METHODS &AMP; VARIABLES: Conditional logistic regression, t test, and Fisher's
      exact tests were used to assess increased risks for IH and the development of a
      prognostic nomogram with signs, symptoms, and laboratory values relevant to IH.
      ?. RESULTS: Composite outcomes for signs, symptoms, and laboratory values were
      included in a prognostic nomogram that had good discriminative ability to predict
      IH, with a bootstrap corrected concordance index of 0.766 (95% confidence
      interval [0.657, 0.866]) and good calibration. Prognostic nomogram predicted
      patients with prolonged activated partial thromboplastin time (APTT) (greater
      than 30.6), headache, and systolic blood pressure (SBP) of 140 or greater were
      more likely to have IH. ?. IMPLICATIONS FOR NURSING: Nurses should recognize that
      patients with the combination of prolonged APTT, SBP of 140 or greater, and
      headache are more likely to have IH.

PMID- 29466343
TI  - Addressing Cancer Pain Inequities Through Intervention
AB  - The Power Over Pain-Coaching (POP-C) intervention was developed to improve
      functional status and decrease pain and pain-related distress among ambulatory
      African American patients with cancer. By bypassing the effects of disparities,
      the POP-C intervention may help to decrease suffering among African American
      patients with cancer pain; consequently, it contributes to improving quality of
      life and addressing social and other determinants of health among members of this
      population. ?.

PMID- 29466344
TI  - Censorship, Then and Now
AB  - As I was thinking about a topic for this editorial, news and social media outlets
      exploded with the announcement that employees at the Centers for Disease Control
      and Prevention (CDC) had been instructed to not use any of seven words or phrases
      in budget documents (diversity, transgender, fetus, unborn child, vulnerable,
      evidence-?based, and science-based). To say that this hit a nerve is an
      understatement. My Twitter feed and email inbox filled with messages of outrage
      and concern, and I must admit I was swept up in the outpouring of anger. A call
      went out for editors of nursing journals to write editorials about this, and I
      was ready to do just that. ?.

PMID- 29466337
TI  - The Beaker phenomenon and the genomic transformation of northwest Europe.
AB  - From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western
      and central Europe, before it disappeared between 2200 and 1800 bc. The forces
      that propelled its expansion are a matter of long-standing debate, and there is
      support for both cultural diffusion and migration having a role in this process.
      Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age
      Europeans, including 226 individuals associated with Beaker-complex artefacts. We
      detected limited genetic affinity between Beaker-complex-associated individuals
      from Iberia and central Europe, and thus exclude migration as an important
      mechanism of spread between these two regions. However, migration had a key role
      in the further dissemination of the Beaker complex. We document this phenomenon
      most clearly in Britain, where the spread of the Beaker complex introduced high
      levels of steppe-related ancestry and was associated with the replacement of
      approximately 90% of Britain's gene pool within a few hundred years, continuing
      the east-to-west expansion that had brought steppe-related ancestry into central
      and northern Europe over the previous centuries.

PMID- 29466345
TI  - Symptom Dimensions as Outcomes in Interventions for Patients With Cancer: A
      Systematic Review
AB  - PROBLEM IDENTIFICATION: Symptom experience in patients with cancer consists of
      several dimensions, often measured descriptively within various populations but
      seldom used as intervention outcomes. This review aims at describing symptom
      dimensions as outcomes of interventions designed to alleviate symptoms in
      patients with cancer and to describe these interventions' effects on at least two
      symptom dimensions. ?. LITERATURE SEARCH: The PRISMA statement for reporting
      systematic reviews was used. Searches were undertaken in various indexing
      sites.?. DATA EVALUATION: Extracted data included design, participants,
      intervention and control group treatment, targeted symptom dimension, and summary
      of results.?. SYNTHESIS: 2,041 articles were identified and 15 were included. The
      symptom dimensions were intensity, distress, prevalence, frequency, consequences,
      and quality. Eleven interventions had significant effect on symptom dimensions,
      mostly on intensity and distress.?. IMPLICATIONS FOR PRACTICE: Oncology nurses
      need clinical skills to be able to understand patients' experiences through their
      narratives. Various interventions are targeted at symptoms, and these need to be
      implemented to provide evidence-based symptom management.

PMID- 29466346
TI  - Oncology Nurses' Knowledge, Confidence, and Practice in Addressing Caregiver
      Strain and Burden
AB  - OBJECTIVES: To describe nurses' practices, confidence, and knowledge of evidence
      based interventions for cancer caregiver strain and burden and to identify
      factors that contribute to these aspects. ?. SAMPLE &AMP; SETTING: 2,055 Oncology
      Nursing Society members completed an emailed survey.?. METHODS &AMP; VARIABLES:
      Pooled analysis of survey results. Variables included the baseline nursing
      assessment, intervention, confidence, knowledge, strategies used, and barriers
      encountered. ?. RESULTS: Nurses tend to overestimate the strength of evidence for
      interventions not shown to be effective and have moderate confidence in assessing
      and intervening with caregivers. Having been an informal caregiver and having
      received care from an informal caregiver were associated with higher reported
      practice and confidence. Major strategies used were referral to social workers
      and others. Barriers reported were financial, caregiver emotional responses, and
      distance. ?. IMPLICATIONS FOR NURSING: An opportunity exists to increase nurses'
      knowledge and confidence in assessment and intervention with caregivers. Greater
      use of technology may help nurses overcome some barriers to working with
      caregivers. Findings can be used to plan continuing education, develop clinical
      processes, and identify resources nurses need to address strain and burden among
      informal caregivers.

PMID- 29466347
TI  - Effects of Peer-Led Interventions for Patients With Cancer: A Meta-Analysis
AB  - PROBLEM IDENTIFICATION: To evaluate the effects of peer-led supportive
      interventions for patients with cancer.?. LITERATURE SEARCH: Six electronic
      databases (EMBASE, MEDLINE(r), Google Scholar, Cochrane Library, ProQuest Medical
      Library, and CINAHL(r)) were searched for articles published from 1997 to May
      2017.?. DATA EVALUATION: A total of 159 studies were identified. Eighteen (16
      randomized, controlled trials [RCTs] and 2 non-RCTs) were eligible for systematic
      review and 16 for meta-analysis. The Cochrane risk of bias tool and Comprehensive
      Meta-Analysis software were used for analysis.?. SYNTHESIS: The authors
      synthesized the results of the effect size of each trial according to cancer
      symptoms, coping, emotional health, quality of life, self-efficacy, sexuality,
      social support, and health-related behaviors. ?. IMPLICATIONS FOR RESEARCH: The
      findings from this study suggest that an additional tiered evaluation that has a
      theoretical underpinning and high-quality methodology is required to confirm the
      efficacy of peer-led supportive interventions within cancer care models.

PMID- 29466348
TI  - Perceived Needs, Preparedness, and Emotional Distress of Male Caregivers of
      Postsurgical Women With Gynecologic Cancer
AB  - OBJECTIVES: To describe the perceived needs, preparedness, and emotional distress
      of male caregivers of postsurgical patients with gynecologic cancer during the
      transition from hospital to home. ?. SAMPLE &AMP; SETTING: 50 male caregivers of
      patients with gynecologic cancer on an inpatient unit at University Hospitals
      Seidman Cancer Center in Cleveland, OH.?. METHODS &AMP; VARIABLES: Caregiver
      needs, perceived preparedness, and emotional distress were measured at admission
      and at one week postdischarge. Instruments included the Comprehensive Needs
      Assessment Tool for Cancer Caregivers, Preparedness for Caregiving Scale, and
      National Comprehensive Cancer Network Distress Thermometer. The analysis
      consisted of descriptive statistics, Spearman's correlations, and univariate
      linear regressions.?. RESULTS: At both time points, male caregivers' greatest
      needs were interaction with the healthcare staff and information. Perceived
      preparedness was not associated with emotional distress. Male caregivers who were
      young, were employed, were unmarried, and had a lower income had greater needs.?.
      IMPLICATIONS FOR NURSING: A relational nursing care approach that maintains
      effective communication with male caregivers is essential. Nurses should broaden
      the caregiver assessment beyond the practical care of the patient.

PMID- 29466349
TI  - "It's Like We Don't Exist": Tailoring Education for Young Women Undergoing
      Surgery for Early-Stage Breast Cancer
AB  - PURPOSE: The implications of a diagnosis and consequent surgical treatment for
      breast cancer may be different for young women compared to older women. This
      study investigated the information requirements of young women to support their
      treatment decision making at diagnosis.?. PARTICIPANTS &AMP; SETTING: A
      purposeful sample of 20 women diagnosed with breast cancer aged 40 years or
      younger who had undergone surgery and had participated in a large cohort study in
      the United Kingdom.?. METHODOLOGIC APPROACH: Audio recordings of semistructured
      interviews were used to reveal information received at the time of surgical
      treatment.?. FINDINGS: Themes identified were types of breast cancer, surgical
      treatments, nonsurgical treatments, fertility, and surgery and after surgery.
      Participants felt that information required throughout treatment was influenced
      by individual life circumstances, such as children or plans for children,
      relationships, and career intentions. Participants felt information was lacking
      on the effects of treatment on body image, reconstructive surgery, and genetic
      predisposition to breast cancer.?. IMPLICATIONS FOR NURSING: Knowledge of the
      information requirements of young women diagnosed with breast cancer allows
      nursing staff to provide tailored support at times identified as most useful.

PMID- 29466350
TI  - Heart Rate Variability Markers as Correlates of Survival in Recipients of
      Hematopoietic Cell Transplantation
AB  - OBJECTIVES: To assess pre-/post-transplantation changes in autonomic tone, as
      measured by heart rate variability (HRV), among patients undergoing hematopoietic
      cell transplantation (HCT) and to look at those changes as they relate to post
      transplantation survival rates. ?. SAMPLE &AMP; SETTING: Data were derived from a
      sample of 27 English-speaking patients undergoing allogeneic or autologous HCT at
      Stanford University. ?. METHODS &AMP; VARIABLES: A survival analysis using the
      Kaplan-Meier estimator was employed to explore whether increased HRV would
      enhance survival probabilities over time among patients undergoing HCT.?.
      RESULTS: An increased probability of survival was significantly related to
      increases in two HRV indexes. IMPLICATIONS FOR NURSING: HRV may be a useful
      predictor of mortality among patients undergoing HCT. Interventions deliverable
      by nurses could be used to enhance HRV for patients identified as being at risk
      for early mortality.

PMID- 29466351
TI  - Understanding Distress in the Hospital: A Qualitative Study Examining Adults With
      Cancer
AB  - PURPOSE: To measure the distress of hospitalized adults with cancer and identify
      strategies and behaviors to manage distress.?. PARTICIPANTS &AMP; SETTING: 185
      adults with cancer hospitalized in a large tertiary hospital in the Midwest.?.
      METHODOLOGIC APPROACH: This study involved a one-time assessment using the
      National Comprehensive Cancer Network's (NCCN's) Distress Thermometer and two
      open-ended questions. Demographic data were reviewed, and responses to open-ended
      questions were analyzed by content analysis. A team approach was used to develop
      and validate themes. ?. FINDINGS: Strategies used by patients to manage distress
      were categorized as taking charge and embracing help. Helpful strategies were
      related to quality of life and relationship with care teams. ?. IMPLICATIONS FOR
      NURSING: Understanding of distress in hospitalized adults with cancer is limited,
      which warrants the attention of healthcare professionals. Study results have
      implications to enhance patient care and to address nationally established
      psychosocial care objectives and NCCN distress screening standards.

PMID- 29466352
TI  - Improving Functional Status in African Americans With Cancer Pain: A Randomized
      Clinical Trial
AB  - OBJECTIVES: To determine the efficacy of the Power Over Pain-Coaching (POP-C)
      intervention to improve functional status among African American outpatients with
      cancer pain.?. SAMPLE &AMP; SETTING: 310 African American patients were recruited
      from an urban comprehensive cancer center. The study took place in the patients'
      homes.?. METHODS &AMP; VARIABLES: A two-group randomized design with repeated
      measures was used. Data were analyzed with linear mixed effects regression
      analysis and structural equation change score models. Variables were pain, pain
      related distress, functional status, perceived control over pain, and the
      following antecedents to control. RESULTS: Functional status was improved in POP
      C participants relative to control group participants (p < 0.05). Distress also
      was differentially decreased (p < 0.05). Pain intensity ratings decreased
      significantly in all patients (p < 0.05). The largest intervention effects were
      observed in the living with pain component. ?. IMPLICATIONS FOR NURSING:
      Perceived control over pain was strongly related to functional status and is
      amenable to interventions using the POP-C intervention components described in
      this article.

PMID- 29466353
TI  - Comparing biosignatures in aged basalt glass from North Pond, Mid-Atlantic Ridge
      and the Louisville Seamount Trail, off New Zealand.
AB  - Microbial life can leave various traces (or biosignatures) in rocks, including
      biotic alteration textures, biominerals, enrichments of certain elements, organic
      molecules, or remnants of DNA. In basalt glass from the ocean floor, microbial
      alteration textures as well as chemical and isotopic biosignatures have been used
      to trace microbial activity. However, little is known about the relationship
      between the physical and chemical nature of the habitat and the prevalent types
      of biosignatures. Here, we report and compare strongly variable biosignatures
      from two different oceanic study sites. We analyzed rock samples for their
      textural biosignatures and associated organic molecules. The biosignatures from
      the 8 Ma North Pond Region, which represents young, well-oxygenated, and
      hydrologically active crust, are characterized by little textural diversity. The
      organic matter associated with those textures shows evidence for the occurrence
      of remnants of complex biomolecules like proteins. Comparably the biosignatures
      from the older Louisville Seamount Trail (~70 Ma) are more texturally diverse,
      but associated with organic molecules that are more degraded. The Louisville
      Seamount has less fresh glass left and decreased permeability, which metabolic
      pathways may dominate that only leave molecular biosignatures without textural
      evidence of glass alteration. We propose that diverse biosignatures in oceanic
      crust may form during different stages of crustal evolution.

PMID- 29466354
TI  - Identification of long-term trends and seasonality in high-frequency water
      quality data from the Yangtze River basin, China.
AB  - Comprehensive understanding of the long-term trends and seasonality of water
      quality is important for controlling water pollution. This study focuses on
      spatio-temporal distributions, long-term trends, and seasonality of water quality
      in the Yangtze River basin using a combination of the seasonal Mann-Kendall test
      and time-series decomposition. The used weekly water quality data were from 17
      environmental stations for the period January 2004 to December 2015. Results show
      gradual improvement in water quality during this period in the Yangtze River
      basin and greater improvement in the Uppermost Yangtze River basin. The larger
      cities, with high GDP and population density, experienced relatively higher
      pollution levels due to discharge of industrial and household wastewater. There
      are higher pollution levels in Xiang and Gan River basins, as indicated by higher
      NH4-N and CODMn concentrations measured at the stations within these basins.
      Significant trends in water quality were identified for the 2004-2015 period.
      Operations of the three Gorges Reservoir (TGR) enhanced pH fluctuations and
      possibly attenuated CODMn, and NH4-N transportation. Finally, seasonal cycles of
      varying strength were detected for time-series of pollutants in river discharge.
      Seasonal patterns in pH indicate that maxima appear in winter, and minima in
      summer, with the opposite true for CODMn. Accurate understanding of long-term
      trends and seasonality are necessary goals of water quality monitoring system
      efforts and the analysis methods described here provide essential information for
      effectively controlling water pollution.

PMID- 29466355
TI  - Epigenome comparisons reveal linkage between gene expression and postnatal
      remodeling of chromatin domain topology.
AB  - Substantial evidence has accumulated linking epigenome change to alterations in
      stem cell function during postnatal development and aging. Yet much remains to be
      learned about causal relationships, and large gaps remain in our understanding of
      epigenome-transcriptome interactions. Here we investigate structural features of
      large histone H3K27me3-enriched regions in human stem cell-like monocytes and
      their dendritic cell derivatives, where the H3K27me3 modification is considered
      to demarcate Polycomb (PcG) domains. Both differentiation- and postnatal
      development-related change are explored, initially by confirming expected
      reciprocal relationships between transcript abundance and span of PcG domains
      overlapping transcribed regions. PcG-associated postnatal transcriptome change
      specific to the stem cell-like monocytes is found to be incompletely explained by
      conventional measures of PcG region structure. To address this, we introduce
      algorithms that quantify local nucleosome-scale conservation of PcG-region
      topology. It is shown that topology-based comparisons can reveal broad
      statistical linkage between postnatal gene down-regulation and epigenome
      remodeling; further, such comparisons provide access to a previously unexplored
      dimension of epigenome architecture.

PMID- 29466357
TI  - Bioerosion by pit-forming, temperate-reef sea urchins: History, rates and broader
      implications.
AB  - Sea urchins are dominant members of rocky temperate reefs around the world. They
      often occur in cavities within the rock, and fit so tightly, it is natural to
      assume they sculpted these "pits." However, there are no experimental data
      demonstrating they bore pits. If they do, what are the rates and consequences of
      bioerosion to nearshore systems? We sampled purple sea urchins,
      Strongylocentrotus purpuratus, from sites with four rock types, three sedimentary
      (two sandstones and one mudstone) and one metamorphic (granite). A year-long
      experiment showed urchins excavated depressions on sedimentary rocks in just
      months. The rate of pit formation varied with rock type and ranged from <5 yr for
      medium-grain sandstone to >100 yr for granite. In the field, there were
      differences in pit size and shapes of the urchins (height:diameter ratio). The
      pits were shallow and urchins flatter at the granite site, and the pits were
      deeper and urchins taller at the sedimentary sites. Although overall pit sizes
      were larger on mudstone than on sandstone, urchin size accounted for this
      difference. A second, short-term experiment, showed the primary mechanism for
      bioerosion was ingestion of the substratum. This experiment eliminated potential
      confounding factors of the year-long experiment and yielded higher bioerosion
      rates. Given the high densities of urchins, large amounts of rock can be
      converted to sediment over short time periods. Urchins on sandstone can excavate
      as much as 11.4 kg m-2 yr-1. On a broader geographic scale, sediment production
      can exceed 100 t ha-1 yr-1, and across their range, their combined bioerosion is
      comparable to the sediment load of many rivers. The phase shift between urchin
      barrens and kelp bed habitats in the North Pacific is controlled by the trophic
      cascade of sea otters. By limiting urchin populations, these apex predators also
      may indirectly control a substantial component of coastal rates of bioerosion.

PMID- 29466356
TI  - Emergence of resistance mutations in simian immunodeficiency virus (SIV)-infected
      rhesus macaques receiving non-suppressive antiretroviral therapy (ART).
AB  - Two SIVmac251-infected rhesus macaques received tenofovir/emtricitabine with
      raltegravir intensification. Viral rebound occurred during treatment and
      sequencing of reverse transcriptase and integrase genes identified multiple
      resistance mutations. Similar to HIV infection, antiretroviral-resistance
      mutations may occur in SIV-infected nonhuman primates receiving nonsuppressive
      ART. As ART administration to nonhuman primates is currently dramatically
      expanding, fueled by both cure research and the study of HIV-related
      comorbidities, viral resistance should be factored in the study design and data
      interpretation.

PMID- 29466358
TI  - Cycle-specific female preferences for visual and non-visual cues in the horse
      (Equus caballus).
AB  - Although female preferences are well studied in many mammals, the possible
      effects of the oestrous cycle are not yet sufficiently understood. Here we
      investigate female preferences for visual and non-visual male traits relative to
      the periodically cycling of sexual proceptivity (oestrus) and inactivity
      (dioestrus), respectively, in the polygynous horse (Equus caballus). We
      individually exposed mares to stallions in four experimental situations: (i)
      mares in oestrus and visual contact to stallions allowed, (ii) mares in oestrus,
      with blinds (wooden partitions preventing visual contact but allowing for
      acoustic and olfactory communication), (iii) mares in dioestrus, no blinds, and
      (iv) mares in dioestrus, with blinds. Contact times of the mares with each
      stallion, defined as the cumulative amount of time a mare was in the vicinity of
      an individual stallion and actively searching contact, were used to rank
      stallions according to each mare's preferences. We found that preferences based
      on visual traits differed significantly from preferences based on non-visual
      traits in dioestrous mares. The mares then showed a preference for older and
      larger males, but only if visual cues were available. In contrast, oestrous mares
      showed consistent preferences with or without blinds, i.e. their preferences were
      mainly based on non-visual traits and could not be predicted by male age or size.
      Stallions who were generally preferred displayed a high libido that may have
      positively influenced female interest or may have been a consequence of it. We
      conclude that the oestrous cycle has a significant influence on female
      preferences for visual and non-visual male traits in the horse.

PMID- 29466359
TI  - CDK activity provides temporal and quantitative cues for organizing genome
      duplication.
AB  - In eukaryotes, the spatial and temporal organization of genome duplication gives
      rise to distinctive profiles of replication origin usage along the chromosomes.
      While it has become increasingly clear that these programs are important for
      cellular physiology, the mechanisms by which they are determined and modulated
      remain elusive. Replication initiation requires the function of cyclin-dependent
      kinases (CDKs), which associate with various cyclin partners to drive cell
      proliferation. Surprisingly, although we possess detailed knowledge of the CDK
      regulators and targets that are crucial for origin activation, little is known
      about whether CDKs play a critical role in establishing the genome-wide pattern
      of origin selection. We have addressed this question in the fission yeast, taking
      advantage of a simplified cell cycle network in which cell proliferation is
      driven by a single cyclin-CDK module. This system allows us to precisely control
      CDK activity in vivo using chemical genetics. First, in contrast to previous
      reports, our results clearly show that distinct cyclin-CDK pairs are not
      essential for regulating specific subsets of origins and for establishing a
      normal replication program. Importantly, we then demonstrate that the timing at
      which CDK activity reaches the S phase threshold is critical for the organization
      of replication in distinct efficiency domains, while the level of CDK activity at
      the onset of S phase is a dose-dependent modulator of overall origin
      efficiencies. Our study therefore implicates these different aspects of CDK
      regulation as versatile mechanisms for shaping the architecture of DNA
      replication across the genome.

PMID- 29466360
TI  - Combining metformin and esomeprazole is additive in reducing sFlt-1 secretion and
      decreasing endothelial dysfunction - implications for treating preeclampsia.
AB  - INTRODUCTION: The discovery of new treatments that prevent or treat preeclampsia
      would be a major advance. Antiangiogenic factors soluble fms-like tyrosine kinase
      1 (sFlt-1) and soluble endoglin (sENG) are secreted in excess from the placenta,
      causing hypertension, endothelial dysfunction, and multiorgan injury. We recently
      identified metformin and esomeprazole as potential treatments for preeclampsia.
      Both reduce placental and endothelial secretion of sFlt-1 and soluble endoglin,
      and reduce endothelial dysfunction. OBJECTIVES: We set out to assess whether
      combining metformin and esomeprazole would additively reduce sFlt-1 and soluble
      endoglin secretion and reduce endothelial dysfunction (verses drug alone).
      Metformin and esomeprazole were added to primary placental cells and tissues, and
      endothelial cells and their effects on sFlt-1 and soluble endoglin secretion were
      assessed in vitro. Tumor necrosis factor-alpha (TNF-alpha) was added to
      endothelial cells to induce dysfunction in vitro. We examined the ability of
      metformin + esomeprazole to rescue TNF-alpha induced vascular cell adhesion
      molecule-1 (VCAM-1) and Endothelin-1 (ET-1) expression, leukocyte adhesion
      (markers of endothelial dysfunction). RESULTS: Combining metformin and
      esomeprazole was additive at reducing sFlt-1 secretion and expression of sFlt-1
      e15a mRNA isoform in primary cytotrophoblast, placental explants and endothelial
      cells. In contrast, no additive reduction in sENG was observed with combined
      metformin and esomeprazole. The low-dose combination of metformin + esomeprazole
      additively reduced TNF-alpha-induced VCAM-1 mRNA, but not VCAM-1 protein
      expression. There was no additive reduction when combining metformin and
      esomeprazole on TNF-alpha induced PBMC adhesion to endothelial cells. However,
      combining metformin and esomeprazole additively reduced ET-1 mRNA expression.
      CONCLUSIONS: In conclusion combining metformin and esomeprazole additively
      reduced secretion of sFlt-1, and markers of endothelial dysfunction. The
      combination of metformin and esomeprazole may provide a more effective treatment
      or prevention for preeclampsia compared to either as single agents.

PMID- 29466361
TI  - Is there relationship between epicardial fat and cardiovascular parameters in
      incident kidney transplant patients? A post-hoc analysis.
AB  - BACKGROUND: Epicardial fat (EF) has been related to increased cardiovascular risk
      in chronic kidney disease patients. Kidney transplantation is associated with
      weight gain, especially within the first 12 months. Recently an association
      between EF and left ventricular mass (LVM) has been suggested in kidney
      transplant (KTX) recipients. OBJECTIVE: Evaluate the EF in KTX recipients and its
      association with cardiovascular parameters in a 12-month follow-up study.
      METHODS: EF volume was determined using thoracic computed tomography. The EF
      progressor group (EF gain) was defined by any increment in EF after 12 months.
      LVM and LVM index were calculated by echocardiography. RESULTS: Ninety-eight
      incident KTX patients [57% men, 41.2 +/- 10.1 years, mean dialysis time prior to
      transplant of 24 (11-60) months] were analyzed. At baseline and after 12 months,
      EF was 318.6 (275.2-392.6) ml and 329.5 (271.7-384.8) ml, respectively (p =
      0.03). When compared to patients who EF decreased (n = 33), those with EF gain (n
      = 65) had a greater increase of body mass index, abdominal circumference and
      blood glucose. These patients also had a lower reduction of LVM index. However in
      the multivariate analysis, there was no difference in LVM index change between
      groups (interaction p = 0.565), even after adjustment for hypertension, glucose
      and coronary calcium score (interaction p = 0.538). CONCLUSION: The impact of EF
      gain on ventricular mass after KTX could not be definitely confirmed. Further
      prospective studies in a large sample of KTX patients should be considered to
      address a possible causal relationship between EF gain and cardiac hypertrophy in
      this population.

PMID- 29466363
TI  - Sex-specific metamorphosis of cypris larvae in the androdioecious barnacle
      Scalpellum scalpellum (Crustacea: Cirripedia: Thoracica) and its implications for
      the adaptive evolution of dwarf males.
AB  - Androdioecy (co-existence of hermaphrodites and dwarf males) is a fascinating yet
      poorly understood phenomenon. The pedunculated barnacle Scalpellum scalpellum is
      an emerging model species for the system. In S. scalpellum, dwarf males and
      hermaphrodites are very different in adult morphology (e.g., in feeding
      structures and reproductive organs), but they share the same larval development
      with nauplii followed by cypris larvae. Recently, it was found that S. scalpellum
      cypris larvae display both genetic and environmental sex determination, but no
      detailed morphological study has yet investigated how the settled cypris larvae
      differ subsequent to settlement. This study investigates the morphological
      aspects of the onset of sex determination in the cyprids of S. scalpellum by
      examining their metamorphosis into either dwarf males or hermaphrodites under
      laboratory conditions. This study emphasizes morphological differences, such as
      size and shape of primordial shell plates, development of a flexible peduncle and
      of thoracopods. It was shown that the cypris larvae start to differ already one
      day after settlement on either a hydroid (leading to hermaphrodites) or an adult
      hermaphrodite (leading to dwarf males). Dwarf males gradually developed an ovoid
      body shape and two pairs of circular scutal and tergal primordia. Such cyprids
      developed neither a carina nor any peduncle or cirri for feeding. The study
      concludes that the dwarf males of S. scalpellum are not just hermaphrodites
      arrested early in development. This entails that dwarf males constitute their own
      separate developmental pathways and points to S. scalpellum dwarf males being
      more specialized than previously stated. Finally, the study compares differences
      in dwarf male morphology between S. scalpellum with two other androdioecious
      species with less specialized dwarf males and use this to discuss evolutionary
      implications for the adaptive evolution of dwarf males across the Cirripedia.

PMID- 29466362
TI  - The influence of speed and size on avian terrestrial locomotor biomechanics:
      Predicting locomotion in extinct theropod dinosaurs.
AB  - How extinct, non-avian theropod dinosaurs moved is a subject of considerable
      interest and controversy. A better understanding of non-avian theropod locomotion
      can be achieved by better understanding terrestrial locomotor biomechanics in
      their modern descendants, birds. Despite much research on the subject, avian
      terrestrial locomotion remains little explored in regards to how kinematic and
      kinetic factors vary together with speed and body size. Here, terrestrial
      locomotion was investigated in twelve species of ground-dwelling bird, spanning a
      1,780-fold range in body mass, across almost their entire speed range. Particular
      attention was devoted to the ground reaction force (GRF), the force that the feet
      exert upon the ground. Comparable data for the only other extant obligate,
      striding biped, humans, were also collected and studied. In birds, all kinematic
      and kinetic parameters examined changed continuously with increasing speed, while
      in humans all but one of those same parameters changed abruptly at the walk-run
      transition. This result supports previous studies that show birds to have a
      highly continuous locomotor repertoire compared to humans, where discrete
      'walking' and 'running' gaits are not easily distinguished based on kinematic
      patterns alone. The influences of speed and body size on kinematic and kinetic
      factors in birds are developed into a set of predictive relationships that may be
      applied to extinct, non-avian theropods. The resulting predictive model is able
      to explain 79-93% of the observed variation in kinematics and 69-83% of the
      observed variation in GRFs, and also performs well in extrapolation tests.
      However, this study also found that the location of the whole-body centre of mass
      may exert an important influence on the nature of the GRF, and hence some caution
      is warranted, in lieu of further investigation.

PMID- 29466364
TI  - Abnormalities in gray matter volume in patients with borderline personality
      disorder and their relation to lifetime depression: A VBM study.
AB  - BACKGROUND: Structural imaging studies of borderline personality disorder (BPD)
      have found regions of reduced cortical volume, but these have varied considerably
      across studies. Reduced hippocampus and amygdala volume have also been a regular
      finding in studies using conventional volumetric measurement. How far comorbid
      major depression, which is common in BPD and can also affect in brain structure,
      influences the findings is not clear. METHODS: Seventy-six women with BPD and 76
      matched controls were examined using whole-brain voxel-based morphometry (VBM).
      The hippocampus and amygdala were also measured, using both conventional volume
      measurement and VBM within a mask restricted to these two subcortical structures.
      Lifetime history of major depression was assessed using structured psychiatric
      interview. RESULTS: At a threshold of p = 0.05 corrected, the BPD patients showed
      clusters of volume reduction in the dorsolateral prefrontal cortex bilaterally
      and in the pregenual/subgenual medial frontal cortex. There was no evidence of
      volume reductions in the hippocampus or amygdala, either on conventional
      volumetry or using VBM masked to these regions. Instead there was evidence of
      right-sided enlargement of these structures. No significant structural
      differences were found between patients with and without lifetime major
      depression. CONCLUSIONS: According to this study, BPD is characterized by a
      restricted pattern of cortical volume reduction involving the dorsolateral
      frontal cortex and the medial frontal cortex, both areas of potential relevance
      for the clinical features of the disorder. Previous findings concerning reduced
      hippocampus and amygdala volume in the disorder are not supported. Brain
      structural findings in BPD do not appear to be explainable on the basis of
      history of associated lifetime major depression.

PMID- 29466365
TI  - Cross-reactive microbial peptides can modulate HIV-specific CD8+ T cell
      responses.
AB  - Heterologous immunity is an important aspect of the adaptive immune response. We
      hypothesized that this process could modulate the HIV-1-specific CD8+ T cell
      response, which has been shown to play an important role in HIV-1 immunity and
      control. We found that stimulation of peripheral blood mononuclear cells (PBMCs)
      from HIV-1-positive subjects with microbial peptides that were cross-reactive
      with immunodominant HIV-1 epitopes resulted in dramatic expansion of HIV-1
      specific CD8+ T cells. Interestingly, the TCR repertoire of HIV-1-specific CD8+ T
      cells generated by ex vivo stimulation of PBMCs using HIV-1 peptide was different
      from that of cells stimulated with cross-reactive microbial peptides in some HIV
      1-positive subjects. Despite these differences, CD8+ T cells stimulated with
      either HIV-1 or cross-reactive peptides effectively suppressed HIV-1 replication
      in autologous CD4+ T cells. These data suggest that exposure to cross-reactive
      microbial antigens can modulate HIV-1-specific immunity.

PMID- 29466366
TI  - Meta-analysis of the clinical behavior of posterior direct resin restorations:
      Low polymerization shrinkage resin in comparison to methacrylate composite resin.
AB  - Polymerization shrinkage of resin composite can compromise the longevity of
      restorations. To minimize this problem, the monomeric composition of composites
      have been modified. The objective of this study was to conduct a meta-analysis to
      assess the clinical behavior of restorations performed with low polymerization
      shrinkage resin composite in comparison with traditional methacrylates-based
      resin composite. This systematic review was registered at Prospero data system
      (CRD42015023940). Studies were searched in the electronic databases PubMed, Web
      of Science, Scopus, Lilacs and EMBASE according to a predefined search strategy.
      The inclusion criteria were as follow: (1) randomized controlled clinical trials
      with at least six months of follow-up; (2) studies investigating composites with
      monomers designed to reduce polymerization shrinkage; (3) studies conducted with
      class I or II restorations in the permanent dentition; and (4) studies that
      assessed at least one of the following criteria: marginal integrity/adaptation,
      marginal discoloration, recurent caries, retention of composite restorations, and
      postoperative sensitivity. Two independent reviewers analyzed the articles to
      determine inclusion and risk of bias. The search conducted in the databases
      resulted in a total of 14,217 studies. After reviewing the references and
      citations, 21 articles remained. The longest clinical follow-up time was 60
      months. The meta-analysis of the data in the included studies demonstrated that
      only one variable (marginal adaptation after 12 months) showed statistically
      significant outcomes, in which methacrylates-based composites presented
      significantly better results than resin composites containing modified monomers.
      The good level of the scientific evidence as well as the overall low risk of bias
      of the included studies indicate that composites with silorane, ormocer or bulk
      fill type modified monomers have a clinical performance similar to conventional
      resin composites.

PMID- 29466367
TI  - Differentiated embryo chondrocyte plays a crucial role in DNA damage response via
      transcriptional regulation under hypoxic conditions.
AB  - Tumor hypoxia contributes to a biologically aggressive phenotype and therapeutic
      resistance. Recent studies have revealed that hypoxia reduces expression of
      several DNA damage recognition and repair (DRR) genes via both hypoxia-inducible
      factor (HIF)-independent and -dependent pathways, and this induced genomic
      instability in cancer cells. We show here that one of the HIF-target genes
      differentiated embryo chondrocyte (DEC)-plays a role in DNA damage response via
      transcriptional repression. Comprehensive gene expression and database analyses
      have revealed systemic repression of DNA-DRR genes in cancer and non-cancer cells
      under hypoxic conditions. Hypoxic repression in typical cases was confirmed by
      quantitative RT-PCR and promoter reporter experiments, and knockdown experiments
      indicated the critical role of DEC2 in such repression. Assessment of histone
      H2AX phosphorylation revealed that recognition and repair of DNA double-strand
      breaks (DSBs) induced by bleomycin or gamma-ray irradiation were attenuated;
      moreover, Cleaved Caspase-3 levels were decreased with pre-conditioning under
      hypoxia: opposing phenomena were ascertained by knockdown of DEC2. Finally, pre
      conditioning under hypoxia decreased the sensitivity of cancer cells to DSBs, and
      knockdown of DEC2 increased gamma-ray sensitivity. These data imply that a
      critical reduction of DNA-DRR occurs via DEC-dependent transcriptional repression
      and suggest that DEC is a potential molecular target for anti-cancer strategies.

PMID- 29466368
TI  - Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial
      cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations.
AB  - Tumour angiogenesis is an important hallmark of cancer and the study of its
      metabolic adaptations, downstream to any cellular change, can reveal attractive
      targets for inhibiting cancer growth. In the tumour microenvironment, endothelial
      cells (ECs) interact with heterogeneous tumour cell types that drive angiogenesis
      and metastasis. In this study we aim to characterize the metabolic alterations in
      ECs influenced by the presence of tumour cells with extreme metastatic abilities.
      Human umbilical vein endothelial cells (HUVECs) were subjected to different
      microenvironmental conditions, such as the presence of highly metastatic PC-3M
      and highly invasive PC-3S prostate cancer cell lines, in addition to the
      angiogenic activator vascular endothelial growth factor (VEGF), under normoxia.
      Untargeted high resolution liquid chromatography-mass spectrometry (LC-MS) based
      metabolomics revealed significant metabolite differences among the various
      conditions and a total of 25 significantly altered metabolites were identified
      including acetyl L-carnitine, NAD+, hypoxanthine, guanine and oleamide, with
      profile changes unique to each of the experimental conditions. Biochemical
      pathway analysis revealed the importance of fatty acid oxidation and nucleotide
      salvage pathways. These results provide a global metabolic preview that could
      help in selectively targeting the ECs aiding in either cancer cell invasion or
      metastasis in the heterogeneous tumour microenvironment.

PMID- 29466370
TI  - Joint optimization of green vehicle scheduling and routing problem with time
      varying speeds.
AB  - Based on an analysis of the congestion effect and changes in the speed of vehicle
      flow during morning and evening peaks in a large- or medium-sized city, the
      piecewise function is used to capture the rules of the time-varying speed of
      vehicles, which are very important in modelling their fuel consumption and CO2
      emission. A joint optimization model of the green vehicle scheduling and routing
      problem with time-varying speeds is presented in this study. Extra wages during
      nonworking periods and soft time-window constraints are considered. A heuristic
      algorithm based on the adaptive large neighborhood search algorithm is also
      presented. Finally, a numerical simulation example is provided to illustrate the
      optimization model and its algorithm. Results show that, (1) the shortest route
      is not necessarily the route that consumes the least energy, (2) the departure
      time influences the vehicle fuel consumption and CO2 emissions and the optimal
      departure time saves on fuel consumption and reduces CO2 emissions by up to 5.4%,
      and (3) extra driver wages have significant effects on routing and departure time
      slot decisions.

PMID- 29466369
TI  - Induction of epigenetic variation in Arabidopsis by over-expression of DNA
      METHYLTRANSFERASE1 (MET1).
AB  - Epigenetic marks such as DNA methylation and histone modification can vary among
      plant accessions creating epi-alleles with different levels of expression
      competence. Mutations in epigenetic pathway functions are powerful tools to
      induce epigenetic variation. As an alternative approach, we investigated the
      potential of over-expressing an epigenetic function, using DNA METHYLTRANSFERASE1
      (MET1) for proof-of-concept. In Arabidopsis thaliana, MET1 controls maintenance
      of cytosine methylation at symmetrical CG positions. At some loci, which contain
      dense DNA methylation in CG- and non-CG context, loss of MET1 causes joint loss
      of all cytosines methylation marks. We find that over-expression of both
      catalytically active and inactive versions of MET1 stochastically generates new
      epi-alleles at loci encoding transposable elements, non-coding RNAs and proteins,
      which results for most loci in an increase in expression. Individual
      transformants share some common phenotypes and genes with altered gene
      expression. Altered expression states can be transmitted to the next generation,
      which does not require the continuous presence of the MET1 transgene. Long-term
      stability and epigenetic features differ for individual loci. Our data show that
      over-expression of MET1, and potentially of other genes encoding epigenetic
      factors, offers an alternative strategy to identify epigenetic target genes and
      to create novel epi-alleles.

PMID- 29466371
TI  - Ezh2 is not required for cardiac regeneration in neonatal mice.
AB  - The neonatal mouse heart has the remarkable capacity to regenerate lost
      myocardium within the first week of life. Neonatal cardiomyocytes re-express
      fetal genes that control cell proliferation after injury to promote regeneration.
      The loss of regenerative capacity of the heart one week after birth coincides
      with repression of a fetal transcriptional program coordinated by epigenetic
      regulators. The histone methyltransferase enhancer of zeste homolog 2 (Ezh2) is a
      repressor of fetal cardiac transcriptional programs and suppresses cardiomyocyte
      cell proliferation, suggesting a potential function in heart regeneration.
      However, it was recently demonstrated that Ezh2 is dispensable for heart
      regeneration in the neonatal heart. Here, we provide evidence supporting this
      finding and demonstrate that Ezh2 deficiency does not affect regeneration of the
      neonatal heart. We inactivated Ezh2 in differentiating embryonic cardiomyocytes,
      which led to depletion of histone H3 trimethylated at lysine 27 (H3K27me3). Ezh2
      deficiency in cardiomyocytes did not affect clearance of the fibrotic scar in
      myocardial infarction (MI) and apical resection models of cardiac injury at post
      natal day 1 (P1). Similarly, cardiomyocyte-specific loss of Ezh2 did not affect
      fibrotic scar size after MI or apical resection at P7, suggesting that it does
      not extend the regenerative time window. Our results demonstrate that Ezh2 is not
      required for innate neonatal cardiac regeneration.

PMID- 29466372
TI  - Evaluating the use of stable isotope analysis to infer the feeding ecology of a
      growing US gray seal (Halichoerus grypus) population.
AB  - Gray seals (Halichoerus grypus) have been rapidly recolonizing the Northeast US
      coast, eliciting concern from the fishing industry. However, the ecological
      effect of this recovery is still unknown and as such, research is needed to
      better understand how the diet composition of gray seals in US waters will
      contribute to the ecological impact. While previous research on seal diets has
      focused on the analysis of hard prey remains, stable isotope analysis presents an
      alternative method that can be used to describe marine mammal diets when direct
      observation is impossible. To address this issue, we used stable isotope analysis
      of gray seal pup vibrissae and lanugo from Monomoy Island, Cape Cod, MA during
      the 2015/2016 winter breeding season to estimate adult female diet composition
      during pregnancy. Stable isotope mixing models (SIMM) suggested adult female gray
      seals were consuming greater amounts of cephalopod prey and less sand lance than
      previously indicated from analysis of hard prey remains. However, using SIMMs to
      estimate the diet composition of gray seals remains difficult due to the large
      number of isotopically similar prey species and uncertainty in tissue-specific,
      stable isotope trophic enrichment factors. Even so, by combining prey sources
      into ecologically informative groups and integrating prior information into SIMMs
      it is possible to obtain additional insights into the diet of this generalist
      predator.

PMID- 29466373
TI  - Observations on the symbiotic relationship between the caridean shrimp Odontonia
      sibogae (Bruce, 1972) and its ascidian host Herdmania momus (Savigny, 1816).
AB  - Symbiotic relationships between shrimps and other invertebrates are a very common
      phenomenon in tropical environments. Although the caridean shrimp-ascidian
      association has been known for many years, the nature of this relationship is
      still unclear. The current study investigated the association between the
      caridean shrimp Odontonia sibogae (Bruce, 1972) and solitary ascidians. A
      combination of field work conducted along the Red Sea coast of Israel and
      laboratory experiments, conducted during 2015-2016, revealed a clear preference
      of the shrimps for the ascidian species Herdmania momus (Savigny, 1816), with a
      low survival ability of the shrimp outside their host's body. The shrimps usually
      inhabit their host as pairs of male and female or pair of females, but never as
      pairs of males. Out of the 53 studied females, 51% were observed to bear between
      156-1,146 embryos, throughout the course of the year. As these ascidian hosts are
      known to create large aggregates, we suggest that males may possibly wander among
      the ascidians occupied by females in order to increase their reproductive
      success. To date, this is the first study to record the shrimp Dactylonia
      ascidicola (Borradaile, 1898) inhabiting the ascidian H. momus; and the first
      study to investigate in depth the ascidian-shrimp association in the Red Sea. It
      thus provides a platform for future research into the physiological and
      behavioral adaptations required for such a unique association.

PMID- 29466374
TI  - Storage in high-barrier pouches increases the sulforaphane concentration in
      broccoli florets.
AB  - Sulforaphane is a phytochemical that is usually found in cruciferous vegetables
      and is known to have a depressive effect on gastric cancer. Preliminary
      investigations showed that the sulforaphane concentration in broccoli (Brassica
      oleracea var. italica) florets increased under anoxia. Therefore, in the present
      study, we examined the effect of different atmospheric conditions on the
      sulforaphane concentration in broccoli and also tested whether there are
      concurrent effects on the concentration of ethanol, which is an unfavorable
      byproduct of fermentation. The sulforaphane concentration in broccoli florets was
      significantly elevated by 1.9- to 2.8-fold after 2 d of storage under hypoxia at
      ca. 0% O2 and ca. 24% CO2 at 20 degrees C, whereas no such increase was observed
      following storage under normoxia at ca. 0% O2 without CO2 at 20 degrees C.
      Furthermore, after 2 d, the sulforaphane concentration under hypoxia was 1.6- to
      2.3-fold higher than that under normoxia. These results suggest that storage
      under hypoxia with high CO2 levels can elevate the sulforaphane concentration in
      broccoli florets. However, the elevated sulforaphane concentration could not be
      maintained beyond 2 d. There was no significant difference in the concentration
      of ethanol between florets that were stored under hypoxia with/without CO2 or
      normoxia at 2 d. However, the ethanol concentrations inside the pouches
      significantly increased between 2 d and 7 d. These findings indicate that the
      quality of broccoli florets can be improved through storage under hypoxia with
      high CO2 levels at 20 degrees C for 2 d.

PMID- 29466375
TI  - Effects of resource-dependent cannibalism on population size distribution and
      individual life history in a case-bearing caddisfly.
AB  - Resource availability often determines the intensity of cannibalism, which has a
      considerable effect on population size distribution and individual life history.
      Larvae of the caddisfly Psilotreta kisoensis build portable cases from
      sedimentary sands and often display cannibalism. For this species, the
      availability of preferable case material is a critical factor that affects larval
      fitness, and material is locally variable depending on the underlying geology. In
      this study, we investigated how sand quality as a case material determines
      cannibalism frequency among larvae and, in turn, how the differential cannibalism
      frequency affects the body-size distribution and voltinism. Rearing experiments
      within a cohort revealed that a bimodal size distribution developed regardless of
      material quality. However, as the preferable material became abundant, the
      proportion of larger to smaller individuals increased. Consecutive experiments
      suggested that smaller larvae were more frequently cannibalized by larger ones
      and excluded from the population when preferable smooth material was abundant.
      This frequent cannibalism resulted in a bimodal size distribution with a
      significantly higher proportion of larger compared to smaller individuals. The
      size-dependent cannibalism was significantly suppressed when the larvae were
      raised in an environment with a scarcity of the preferable case material. This is
      probably because larvae cannot enjoy the benefit of rapid growth by cannibalism
      due to the difficulties in enlarging their case. At low cannibalism the growth of
      smaller individuals was stunted, and this was probably due to risk of cannibalism
      by larger individuals. This growth reduction in small individuals led to a
      bimodal size-distribution but with a lower proportion of larger to smaller
      individuals compared to at high cannibalism. A field study in two streams showed
      a similar size distribution of larvae as was found in the rearing experiment. The
      bimodal ratio has consequences for life history, since a size-bimodal population
      causes a cohort splitting: only larvae that were fully grown at 1 year had a
      univoltine life cycle, whereas larvae with a stunted growth continued their
      larval life for another year (semivoltine). This study suggests that availability
      of preferable case building material is an important factor that affects
      cannibalism, which in turn affects larval population size structure and cohort
      splitting.

PMID- 29466376
TI  - Endosymbiont-based immunity in Drosophila melanogaster against parasitic nematode
      infection.
AB  - Associations between endosymbiotic bacteria and their hosts represent a complex
      ecosystem within organisms ranging from humans to protozoa. Drosophila species
      are known to naturally harbor Wolbachia and Spiroplasma endosymbionts, which play
      a protective role against certain microbial infections. Here, we investigated
      whether the presence or absence of endosymbionts affects the immune response of
      Drosophila melanogaster larvae to infection by Steinernema carpocapsae nematodes
      carrying or lacking their mutualistic Gram-negative bacteria Xenorhabdus
      nematophila (symbiotic or axenic nematodes, respectively). We find that the
      presence of Wolbachia alone or together with Spiroplasma promotes the survival of
      larvae in response to infection with S. carpocapsae symbiotic nematodes, but not
      against axenic nematodes. We also find that Wolbachia numbers are reduced in
      Spiroplasma-free larvae infected with axenic compared to symbiotic nematodes, and
      they are also reduced in Spiroplasma-containing compared to Spiroplasma-free
      larvae infected with axenic nematodes. We further show that S. carpocapsae axenic
      nematode infection induces the Toll pathway in the absence of Wolbachia, and that
      symbiotic nematode infection leads to increased phenoloxidase activity in D.
      melanogaster larvae devoid of endosymbionts. Finally, infection with either type
      of nematode alters the metabolic status and the fat body lipid droplet size in D.
      melanogaster larvae containing only Wolbachia or both endosymbionts. Our results
      suggest an interaction between Wolbachia endosymbionts with the immune response
      of D. melanogaster against infection with the entomopathogenic nematodes S.
      carpocapsae. Results from this study indicate a complex interplay between insect
      hosts, endosymbiotic microbes and pathogenic organisms.

PMID- 29466377
TI  - Understanding the psychiatric effects of concussion on constructed identity in
      hockey players: Implications for health professionals.
AB  - OBJECTIVE: The following study was undertaken to investigate the effect of
      concussion and psychiatric illness on athletes and their caregivers. METHODS:
      Semi-structured interviews with 20 ice hockey stakeholders (17 men and 3 women)
      including minor and professional players, coaches, parents, and physicians were
      conducted over two years (2012-2014). These interviews were analyzed using
      grounded theory. RESULTS: From this analysis, a common biographical theme emerged
      whereby the subject's identity as a hockey player, constructed early in life over
      many years, was disrupted by concussion. Furthermore, some players underwent a
      biographical deconstruction when they experienced post-concussive mental illness,
      which was amplified by isolation, stigma from peers, and lack of a clear life
      trajectory. Many players obtained support from family and peers and were able to
      recover, as evidenced by the biographical reconstruction of their identity post
      hockey concussion. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Understanding the
      process of biographical deconstruction and reconstruction has significant
      psychosocial treatment implications for both healthcare professionals and
      caregivers of this population. Specifically, the authors suggest that
      interpersonal psychotherapy (IPT) that focuses on role transitions may create
      opportunities to facilitate the process of biographical reconstruction and life
      transition.

PMID- 29466378
TI  - Crystal structure of a cold-active protease (Pro21717) from the psychrophilic
      bacterium, Pseudoalteromonas arctica PAMC 21717, at 1.4 A resolution: Structural
      adaptations to cold and functional analysis of a laundry detergent enzyme.
AB  - Enzymes isolated from organisms found in cold habitats generally exhibit higher
      catalytic activity at low temperatures than their mesophilic homologs and are
      therefore known as cold-active enzymes. Cold-active proteases are very useful in
      a variety of biotechnological applications, particularly as active ingredients in
      laundry and dishwashing detergents, where they provide strong protein-degrading
      activity in cold water. We identified a cold-active protease (Pro21717) from a
      psychrophilic bacterium, Pseudoalteromonas arctica PAMC 21717, and determined the
      crystal structure of its catalytic domain (CD) at a resolution of 1.4 A. The
      Pro21717-CD structure shows a conserved subtilisin-like fold with a typical
      catalytic triad (Asp185, His244, and Ser425) and contains four calcium ions and
      three disulfide bonds. Interestingly, we observed an unexpected electron density
      at the substrate-binding site from a co-purified peptide. Although the sequence
      of this peptide is unknown, analysis of the peptide-complexed structure
      nonetheless provides some indication of the substrate recognition and binding
      mode of Pro21717. Moreover, various parameters, including a wide substrate pocket
      size, an abundant active-site loop content, and a flexible structure provide
      potential explanations for the cold-adapted properties of Pro21717. In
      conclusion, this is first structural characterization of a cold-adapted
      subtilisin-like protease, and these findings provide a structural and functional
      basis for industrial applications of Pro21717 as a cold-active laundry or
      dishwashing detergent enzyme.

PMID- 29466379
TI  - Activation of retinal glial (Muller) cells by extracellular ATP induces
      pronounced increases in extracellular H+ flux.
AB  - Small alterations in extracellular acidity are potentially important modulators
      of neuronal signaling within the vertebrate retina. Here we report a novel
      extracellular acidification mechanism mediated by glial cells in the retina.
      Using self-referencing H+-selective microelectrodes to measure extracellular H+
      fluxes, we show that activation of retinal Muller (glial) cells of the tiger
      salamander by micromolar concentrations of extracellular ATP induces a pronounced
      extracellular H+ flux independent of bicarbonate transport. ADP, UTP and the non
      hydrolyzable analog ATPgammas at micromolar concentrations were also potent
      stimulators of extracellular H+ fluxes, but adenosine was not. The extracellular
      H+ fluxes induced by ATP were mimicked by the P2Y1 agonist MRS 2365 and were
      significantly reduced by the P2 receptor blockers suramin and PPADS, suggesting
      activation of P2Y receptors. Bath-applied ATP induced an intracellular rise in
      calcium in Muller cells; both the calcium rise and the extracellular H+ fluxes
      were significantly attenuated when calcium re-loading into the endoplasmic
      reticulum was inhibited by thapsigargin and when the PLC-IP3 signaling pathway
      was disrupted with 2-APB and U73122. The anion transport inhibitor DIDS also
      markedly reduced the ATP-induced increase in H+ flux while SITS had no effect.
      ATP-induced H+ fluxes were also observed from Muller cells isolated from human,
      rat, monkey, skate and lamprey retinae, suggesting a highly evolutionarily
      conserved mechanism of potential general importance. Extracellular ATP also
      induced significant increases in extracellular H+ flux at the level of both the
      outer and inner plexiform layers in retinal slices of tiger salamander which was
      significantly reduced by suramin and PPADS. We suggest that the novel H+ flux
      mediated by ATP-activation of Muller cells and of other glia as well may be a key
      mechanism modulating neuronal signaling in the vertebrate retina and throughout
      the brain.

PMID- 29466380
TI  - Q fever in Egypt: Epidemiological survey of Coxiella burnetii specific antibodies
      in cattle, buffaloes, sheep, goats and camels.
AB  - Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. Clinical
      presentation in humans varies from asymptomatic to flu-like illness and severe
      sequelae may be seen. Ruminants are often sub-clinically infected or show
      reproductive disorders such as abortions. In Egypt, only limited data on the
      epidemiology of Q fever in animals are available. Using a stratified two stage
      random sampling approach, we evaluated the prevalence of Coxiella burnetii
      specific antibodies among ruminants and camels in 299 herds. A total of 2,699
      blood samples was investigated using enzyme-linked-immunosorbent assay (ELISA).
      Coxiella burnetii specific antibodies were detected in 40.7% of camels (215/528),
      19.3% of cattle (162/840), 11.2% of buffaloes (34/304), 8.9% of sheep (64/716)
      and 6.8% of goats (21/311), respectively. Odds of seropositivity were
      significantly higher for cattle (aOR: 3.17; 95% CI: 1.96-5.13) and camels (aOR:
      9.75; 95% CI: 6.02-15.78). Significant differences in seropositivity were also
      found between domains (Western Desert, Eastern Desert and Nile Valley and Delta)
      and 25 governorates (p < 0.001), respectively. Animal rearing in the Eastern
      Desert domain was found to be a significant risk factor (aOR: 2.16; 95% CI: 1.62
      2.88). Most seropositive animals were older than four years. No correlation
      between positive titers and husbandry practices or animal origin were found (p >
      0.05). Only 8.7% of the interviewed people living on the farms consumed raw camel
      milk and none reported prior knowledge on Q fever. Findings from this nationwide
      study show that exposure to Coxiella burnetii is common in ruminants and camels.
      Disease awareness among physicians, veterinarians and animal owners has to be
      raised. Future epidemiological investigations have to elucidate the impact of Q
      fever on human health and on the economy of Egypt.

PMID- 29466381
TI  - Transmission of fungal partners to incipient Cecropia-tree ant colonies.
AB  - Ascomycete fungi in the nests of ants inhabiting plants (= myrmecophytes) are
      very often cultivated by the ants in small patches and used as food source. Where
      these fungi come from is not known yet. Two scenarios of fungus recruitment are
      possible: (1) random infection through spores or hyphal fragments from the
      environment, or (2) transmission from mother to daughter colonies by the
      foundress queen. It is also not known at which stage of the colony life cycle
      fungiculture is initiated, and whether the- symbiont fungi serve as food for the
      ant queen. To clarify these questions, we investigated four Azteca ant species
      inhabiting three different Cecropia species (C. insignis, C. obtusifolia, and C.
      peltata). We analysed an rRNA gene fragment from 52 fungal patches produced by
      founding queens and compared them with those from established Azteca colonies (n
      = 54). The infrabuccal pockets of winged queens were dissected to investigate
      whether young queens carry fungi from their mother colony. Additionally, 15N
      labelling experiments were done to verify whether the queen feeds on the patches
      until she is nourished by her first worker offspring. We infer from the results
      that the fungi cultivated in hollow plant structures are transferred from the
      parental colony of the young queen. First, fungal genotypes/OTU diversity was not
      significantly different between foundress queen patches and established colonies,
      and second, hyphal parts were discovered in the infrabuccal pockets of female
      alates. We could show that fungiculture already starts before queens lay their
      eggs, and that the queens do not feed on fungal patch material but feed it to the
      larvae. Our findings suggest that fungiculture may be crucial for successful
      colony founding of arboreal ants in the tropics.

PMID- 29466382
TI  - Mating and aggregative behaviors among basal hexapods in the Early Cretaceous.
AB  - Among the many challenges in paleobiology is the inference and reconstruction of
      behaviors that rarely, if ever, leave a physical trace on the environment that is
      suitable for fossilization. Of particular significance are those behaviors tied
      to mating and courtship, individual interactions critical for species integrity
      and continuance, as well as those for dispersal, permitting the taxon to expand
      its distribution as well as access new habitats in the face of local or long-term
      environmental change. In this context, two recently discovered fossils from the
      Early Cretaceous amber of Spain (ca. 105 mya) give a detailed view of otherwise
      fleeting ethologies in Collembola. These occurrences are phylogenetically spaced
      across the class, and from species representing the two major clades of
      springtails-Symphypleona and Entomobryomorpha. Specifically, we report unique
      evidence from a symphypleonan male (Pseudosminthurides stoechus Sanchez-Garcia &
      Engel, 2016) with modified antennae that may have functioned as a clasping organ
      for securing females during mating on water's surface, and from an aggregation of
      entomobryomorphan individuals (Proisotoma communis Sanchez-Garcia & Engel, 2016)
      purportedly representing a swarming episode on the forest floor. We demonstrate
      that the mating behavioral repertoire in P. stoechus, which is associated with
      considerable morphological adaptations, likely implied elaborate courtship and
      maneuvering for guarantee sperm transfer in an epineustic species. These
      discoveries reveal significant behaviors consistent with modern counterparts and
      a generalized stasis for some ancient hexapod ethologies associated with complex
      mating and courtship and social or pre-social aggregations, so critical to
      specific constancy and dispersal.

PMID- 29466384
TI  - Archaeological application of airborne LiDAR to examine social changes in the
      Ceibal region of the Maya lowlands.
AB  - Although the application of LiDAR has made significant contributions to
      archaeology, LiDAR only provides a synchronic view of the current topography. An
      important challenge for researchers is to extract diachronic information over
      typically extensive LiDAR-surveyed areas in an efficient manner. By applying an
      architectural chronology obtained from intensive excavations at the site center
      and by complementing it with surface collection and test excavations in
      peripheral zones, we analyze LiDAR data over an area of 470 km2 to trace social
      changes through time in the Ceibal region, Guatemala, of the Maya lowlands. We
      refine estimates of structure counts and populations by applying commission and
      omission error rates calculated from the results of ground-truthing. Although the
      results of our study need to be tested and refined with additional research in
      the future, they provide an initial understanding of social processes over a wide
      area. Ceibal appears to have served as the only ceremonial complex in the region
      during the transition to sedentism at the beginning of the Middle Preclassic
      period (c. 1000 BC). As a more sedentary way of life was accepted during the late
      part of the Middle Preclassic period and the initial Late Preclassic period (600
      300 BC), more ceremonial assemblages were constructed outside the Ceibal center,
      possibly symbolizing the local groups' claim to surrounding agricultural lands.
      From the middle Late Preclassic to the initial Early Classic period (300 BC-AD
      300), a significant number of pyramidal complexes were probably built. Their high
      concentration in the Ceibal center probably reflects increasing political
      centralization. After a demographic decline during the rest of the Early Classic
      period, the population in the Ceibal region reached the highest level during the
      Late and Terminal Classic periods, when dynastic rule was well established (AD
      600-950).

PMID- 29466383
TI  - Stroke survivors' and informal caregivers' experiences of primary care and
      community healthcare services - A systematic review and meta-ethnography.
AB  - OBJECTIVE: To describe and explain stroke survivors and informal caregivers'
      experiences of primary care and community healthcare services. To offer potential
      solutions for how negative experiences could be addressed by healthcare services.
      DESIGN: Systematic review and meta-ethnography. DATA SOURCES: Medline, CINAHL,
      Embase and PsycINFO databases (literature searched until May 2015, published
      studies ranged from 1996 to 2015). ELIGIBILITY CRITERIA: Primary qualitative
      studies focused on adult community-dwelling stroke survivors' and/or informal
      caregivers' experiences of primary care and/or community healthcare services.
      DATA SYNTHESIS: A set of common second order constructs (original authors'
      interpretations of participants' experiences) were identified across the studies
      and used to develop a novel integrative account of the data (third order
      constructs). Study quality was assessed using the Critical Appraisal Skills
      Programme checklist. Relevance was assessed using Dixon-Woods' criteria. RESULTS:
      51 studies (including 168 stroke survivors and 328 caregivers) were synthesised.
      We developed three inter-dependent third order constructs: (1) marginalisation of
      stroke survivors and caregivers by healthcare services, (2) passivity versus
      proactivity in the relationship between health services and the patient/caregiver
      dyad, and (3) fluidity of stroke related needs for both patient and caregiver.
      Issues of continuity of care, limitations in access to services and inadequate
      information provision drove perceptions of marginalisation and passivity of
      services for both patients and caregivers. Fluidity was apparent through changing
      information needs and psychological adaptation to living with long-term
      consequences of stroke. LIMITATIONS: Potential limitations of qualitative
      research such as limited generalisability and inability to provide firm answers
      are offset by the consistency of the findings across a range of countries and
      healthcare systems. CONCLUSIONS: Stroke survivors and caregivers feel abandoned
      because they have become marginalised by services and they do not have the
      knowledge or skills to re-engage. This can be addressed by: (1) increasing stroke
      specific health literacy by targeted and timely information provision, and (2)
      improving continuity of care between specialist and generalist services.
      SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO 2015:CRD42015026602.

PMID- 29466385
TI  - Adherence to antiretroviral therapy in a clinical cohort of HIV-infected children
      in East Africa.
AB  - OBJECTIVE: To describe antiretroviral therapy (ART) adherence and associated
      factors for a large HIV-infected pediatric cohort followed by sites of the East
      Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) consortium.
      METHODS: This study utilized prospectively collected clinical data from HIV
      infected children less than 13 years of age who initiated ART within 4 clinical
      care programs (with 26 clinical sites) in Kenya, Uganda, and Tanzania and were
      followed for up to 6 years. Programs used one of 3 adherence measures, including
      7-day quantitative recall, 7-day categorical recall, and clinician pill
      assessments. We fit a hierarchical, three-level, logistic-regression model to
      examine adherence, with observations nested within patient, and patients within
      the 26 sites providing pediatric HIV data to this analysis. RESULTS: In East
      Africa, 3,304 children, 52.0% male, were enrolled in care and were subsequently
      observed for a median of 92 weeks (inter-quartile range [IQR] 50.3-145.0 weeks).
      Median age at ART initiation was 5.5 years ([IQR] 3.0-8.5 years). "Good"
      adherence, as reported by each clinic's measures, was extremely high, remaining
      on average above 90% throughout all years of follow-up. Longer time on ART was
      associated with higher adherence (adjusted Odds Ratio-aOR-per log-transformed
      week on ART: 1.095, 95% Confidence Interval-CI-[1.052-1.150].) Patients enrolled
      in higher-volume programs exhibited higher rates of clinician-assessed adherence
      (aOR per log-500 patients: 1.174, 95% CI [1.108-1.245]). Significant site-level
      variability in reported adherence was observed (0.28), with even higher
      variability among patients (0.71). In a sub-analysis, being an orphan at the
      start of ART was strongly associated with lower ART adherence rates (aOR: 0.919,
      95% CI [0.864-0.976]). CONCLUSIONS: Self-reported adherence remained high over a
      median of 1.8 years in HIV care, but varied according to patient-level and site
      level factors. Consistent adherence monitoring with validated measures and
      attention to vulnerable groups is recommended.

PMID- 29466386
TI  - The Arabidopsis arc5 and arc6 mutations differentially affect plastid morphology
      in pavement and guard cells in the leaf epidermis.
AB  - Chloroplasts, or photosynthetic plastids, multiply by binary fission, forming a
      homogeneous population in plant cells. In Arabidopsis thaliana, the division
      apparatus (or division ring) of mesophyll chloroplasts includes an inner envelope
      transmembrane protein ARC6, a cytoplasmic dynamin-related protein ARC5 (DRP5B),
      and members of the FtsZ1 and FtsZ2 families of proteins, which co-assemble in the
      stromal mid-plastid division ring (FtsZ ring). FtsZ ring placement is controlled
      by several proteins, including a stromal factor MinE (AtMinE1). During leaf
      mesophyll development, ARC6 and AtMinE1 are necessary for FtsZ ring formation and
      thus plastid division initiation, while ARC5 is essential for a later stage of
      plastid division. Here, we examined plastid morphology in leaf epidermal pavement
      cells (PCs) and stomatal guard cells (GCs) in the arc5 and arc6 mutants using
      stroma-targeted fluorescent proteins. The arc5 PC plastids were generally a bit
      larger than those of the wild type, but most had normal shapes and were division
      competent, unlike mutant mesophyll chloroplasts. The arc6 PC plastids were
      heterogeneous in size and shape, including the formation of giant and mini
      plastids, plastids with highly developed stromules, and grape-like plastid
      clusters, which varied on a cell-by-cell basis. Moreover, unique plastid
      phenotypes for stomatal GCs were observed in both mutants. The arc5 GCs rarely
      lacked chlorophyll-bearing plastids (chloroplasts), while they accumulated minute
      chlorophyll-less plastids, whereas most GCs developed wild type-like
      chloroplasts. The arc6 GCs produced large chloroplasts and/or chlorophyll-less
      plastids, as previously observed, but unexpectedly, their chloroplasts/plastids
      exhibited marked morphological variations. We quantitatively analyzed plastid
      morphology and partitioning in paired GCs from wild-type, arc5, arc6, and atminE1
      plants. Collectively, our results support the notion that ARC5 is dispensable in
      the process of equal division of epidermal plastids, and indicate that
      dysfunctions in ARC5 and ARC6 differentially affect plastid replication among
      mesophyll cells, PCs, and GCs within a single leaf.

PMID- 29466387
TI  - Overexpression of the alfalfa WRKY11 gene enhances salt tolerance in soybean.
AB  - The WRKY transcription factors play an important role in the regulation of
      transcriptional reprogramming associated with plant abiotic stress responses. In
      this study, the WRKY transcription factor MsWRKY11, containing the plant-specific
      WRKY zinc finger DNA-binding motif, was isolated from alfalfa. The MsWRKY11 gene
      was detected in all plant tissues (root, stem, leaf, flower, and fruit), with
      high expression in root and leaf tissues. MsWRKY11 was upregulated in response to
      a variety of abiotic stresses, including salinity, alkalinity, cold, abscisic
      acid, and drought. Overexpression of MsWRKY11 in soybean enhanced the salt
      tolerance at the seedling stage. Transgenic soybean had a better salt-tolerant
      phenotype, and the hypocotyls were significantly longer than those of wild-type
      seeds after salt treatment. Furthermore, MsWRKY11 overexpression increased the
      contents of chlorophyll, proline, soluble sugar, superoxide dismutase, and
      catalase, but reduced the relative electrical conductivity and the contents of
      malonaldehyde, H2O2, and O2-. Plant height, pods per plant, seeds per plant, and
      100-seed weight of transgenic MsWRKY11 soybean were higher than those of wild
      type soybean, especially OX2. Results of the salt experiment showed that MsWRKY11
      is involved in salt stress responses, and its overexpression improves salt
      tolerance in soybean.

PMID- 29466388
TI  - Prospecting for viral natural enemies of the fire ant Solenopsis invicta in
      Argentina.
AB  - Metagenomics and next generation sequencing were employed to discover new virus
      natural enemies of the fire ant, Solenopsis invicta Buren in its native range
      (i.e., Formosa, Argentina) with the ultimate goal of testing and releasing new
      viral pathogens into U.S. S. invicta populations to provide natural, sustainable
      control of this ant. RNA was purified from worker ants from 182 S. invicta
      colonies, which was pooled into 4 groups according to location. A library was
      created from each group and sequenced using Illumina Miseq technology. After a
      series of winnowing methods to remove S. invicta genes, known S. invicta virus
      genes, and all other non-virus gene sequences, 61,944 unique singletons were
      identified with virus identity. These were assembled de novo yielding 171
      contiguous sequences with significant identity to non-plant virus genes. Fifteen
      contiguous sequences exhibited very high expression rates and were detected in
      all four gene libraries. One contig (Contig_29) exhibited the highest expression
      level overall and across all four gene libraries. Random amplification of cDNA
      ends analyses expanded this contiguous sequence yielding a complete virus genome,
      which we have provisionally named Solenopsis invicta virus 5 (SINV-5). SINV-5 is
      a positive-sense, single-stranded RNA virus with genome characteristics
      consistent with insect-infecting viruses from the family Dicistroviridae.
      Moreover, the replicative genome strand of SINV-5 was detected in worker ants
      indicating that S. invicta serves as host for the virus. Many additional
      sequences were identified that are likely of viral origin. These sequences await
      further investigation to determine their origins and relationship with S.
      invicta. This study expands knowledge of the RNA virome diversity found within S.
      invicta populations.

PMID- 29466389
TI  - Mapping integration of midwives across the United States: Impact on access,
      equity, and outcomes.
AB  - METHODS: Our multidisciplinary team examined published regulatory data to inform
      a 50-state database describing the environment for midwifery practice and
      interprofessional collaboration. Items (110) detailed differences across
      jurisdictions in scope of practice, autonomy, governance, and prescriptive
      authority; as well as restrictions that can affect patient safety, quality, and
      access to maternity providers across birth settings. A nationwide survey of state
      regulatory experts (n = 92) verified the 'on the ground' relevance, importance,
      and realities of local interpretation of these state laws. Using a modified
      Delphi process, we selected 50/110 key items to include in a weighted, composite
      Midwifery Integration Scoring (MISS) system. Higher scores indicate greater
      integration of midwives across all settings. We ranked states by MISS scores;
      and, using reliable indicators in the CDC-Vital Statistics Database, we
      calculated correlation coefficients between MISS scores and maternal-newborn
      outcomes by state, as well as state density of midwives and place of birth. We
      conducted hierarchical linear regression analysis to control for confounding
      effects of race. RESULTS: MISS scores ranged from lowest at 17 (North Carolina)
      to highest at 61 (Washington), out of 100 points. Higher MISS scores were
      associated with significantly higher rates of spontaneous vaginal delivery,
      vaginal birth after cesarean, and breastfeeding, and significantly lower rates of
      cesarean, preterm birth, low birth weight infants, and neonatal death. MISS
      scores also correlated with density of midwives and access to care across birth
      settings. Significant differences in newborn outcomes accounted for by MISS
      scores persisted after controlling for proportion of African American births in
      each state. CONCLUSION: The MISS scoring system assesses the level of integration
      of midwives and evaluates regional access to high quality maternity care. In the
      United States, higher MISS Scores were associated with significantly higher rates
      of physiologic birth, less obstetric interventions, and fewer adverse neonatal
      outcomes.

PMID- 29466390
TI  - The role of complement activation in rhabdomyolysis-induced acute kidney injury.
AB  - Rhabdomyolysis (RM) may cause kidney damage and results primarily in acute kidney
      injury (AKI). Complement is implicated in the pathogenesis of renal diseases and
      ischemia-reperfusion injury (IRI), but the role of complement, especially its
      activation pathway(s) and its effect in RM-induced AKI, is not clear. This study
      established a rat model of AKI induced by RM via intramuscular treatment with
      glycerol. Cobra venom factor (CVF) was administered via tail vein injection to
      deplete complement 12 h prior to intramuscular injection of glycerol. We found
      that the complement components, including complement 3 (C3), C1q, MBL-A, factor
      B(fB), C5a, C5b-9, and CD59, were significantly increased in rat kidneys after
      intramuscular glycerol administration. However, the levels of serum BUN and Cr,
      renal tubular injury scores, and the number of TUNEL-positive cells decreased
      significantly in the CVF+AKI group. These results suggest that complement plays
      an important role in RM-induced AKI and that complement depletion may improve
      renal function and decrease renal tissue damage by reducing the inflammatory
      response and apoptosis.

PMID- 29466391
TI  - A standardised equine-based welfare assessment tool used for six years in low and
      middle income countries.
AB  - The majority of horses, donkeys and mules (equids) are in low- and middle-income
      countries, where they remain a key source of labour in the construction,
      agriculture and tourism industries, as well as supporting households daily
      through transporting people and staple goods. Globally, approximately 600 million
      people depend on working equids for their livelihood. Safeguarding the welfare of
      these animals is essential for them to work, as well as for the intrinsic value
      of the animal's quality of life. In order to manage animal welfare, it must be
      measured. Over the past decade, welfare assessment methodologies have emerged for
      different species, more recently for equids. We present the Standardised Equine
      Based Welfare Assessment Tool (SEBWAT) for working equids. The tool is unique, in
      that it has been applied in practice by a non-governmental organisation (NGO) for
      six years across Low-Middle-Income Countries (LMICs). We describe the revision of
      the tool from an original to a second version, the tool methodology and user
      training process and how data collection and analysis have been conducted. We
      describe its application at scale, where it has been used more than 71,000 times
      in 11 countries. Case study examples are given from the tool being used for a
      needs assessment in Guatemala and monitoring welfare change in Jordan. We
      conclude by describing the main benefits and limitations for how the tool could
      be applied by others on working equids in LMICs and how it may develop in the
      future.

PMID- 29466392
TI  - Differences between co-cultures and monocultures in testing the toxicity of
      particulate matter derived from log wood and pellet combustion.
AB  - BACKGROUND: In vitro studies with monocultures of human alveolar cells shed
      deeper knowledge on the cellular mechanisms by which particulate matter (PM)
      causes toxicity, but cannot account for mitigating or aggravating effects of cell
      cell interactions on PM toxicity. METHODS: We assessed inflammation, oxidative
      stress as well as cytotoxic and genotoxic effects induced by PM from the
      combustion of different types of wood logs and softwood pellets in three cell
      culture setups: two monocultures of either human macrophage-like cells or human
      alveolar epithelial cells, and a co-culture of these two cell lines. The adverse
      effects of the PM samples were compared between these setups. RESULTS: We
      detected clear differences in the endpoints between the mono- and co-cultures.
      Inflammatory responses were more diverse in the macrophage monoculture and the co
      culture compared to the epithelial cells where only an increase of IL-8 was
      detected. The production of reactive oxygen species was the highest in epithelial
      cells and macrophages seemed to have protective effects against oxidative stress
      from the PM samples. With no metabolically active cells at the highest doses, the
      cytotoxic effects of the PM samples from the wood log combustion were far more
      pronounced in the macrophages and the co-culture than in the epithelial cells.
      All samples caused DNA damage in macrophages, whereas only beech and spruce log
      combustion samples caused DNA damage in epithelial cells. The organic content of
      the samples was mainly associated with cytotoxicity and DNA damage, while the
      metal content of the samples correlated with the induction of inflammatory
      responses. CONCLUSIONS: All of the tested PM samples induce adverse effects and
      the chemical composition of the samples determines which pathway of toxicity is
      induced. In vitro testing of the toxicity of combustion-derived PM in
      monocultures of one cell line, however, is inadequate to account for all the
      possible pathways of toxicity.

PMID- 29466394
TI  - A hybrid intelligent method for three-dimensional short-term prediction of
      dissolved oxygen content in aquaculture.
AB  - A precise predictive model is important for obtaining a clear understanding of
      the changes in dissolved oxygen content in crab ponds. Highly accurate interval
      forecasting of dissolved oxygen content is fundamental to reduce risk, and three
      dimensional prediction can provide more accurate results and overall guidance. In
      this study, a hybrid three-dimensional (3D) dissolved oxygen content prediction
      model based on a radial basis function (RBF) neural network, K-means and
      subtractive clustering was developed and named the subtractive clustering (SC)-K
      means-RBF model. In this modeling process, K-means and subtractive clustering
      methods were employed to enhance the hyperparameters required in the RBF neural
      network model. The comparison of the predicted results of different traditional
      models validated the effectiveness and accuracy of the proposed hybrid SC-K-means
      RBF model for three-dimensional prediction of dissolved oxygen content.
      Consequently, the proposed model can effectively display the three-dimensional
      distribution of dissolved oxygen content and serve as a guide for feeding and
      future studies.

PMID- 29466393
TI  - The effect of low and high-intensity cycling in diesel exhaust on flow-mediated
      dilation, circulating NOx, endothelin-1 and blood pressure.
AB  - INTRODUCTION: Exposure to air pollution impairs aspects of endothelial function
      such as flow-mediated dilation (FMD). Outdoor exercisers are frequently exposed
      to air pollution, but how exercising in air pollution affects endothelial
      function and how these effects are modified by exercise intensity are poorly
      understood. OBJECTIVES: Therefore, the purpose of this study was to determine the
      effects of low-intensity and high-intensity cycling with diesel exhaust (DE)
      exposure on FMD, blood pressure, plasma nitrite and nitrate (NOx) and endothelin
      1. METHODS: Eighteen males performed 30-minute trials of low or high-intensity
      cycling (30% and 60% of power at VO2peak) or a resting control condition. For
      each subject, each trial was performed once while breathing filtered air (FA) and
      once while breathing DE (300ug/m3 of PM2.5, six trials in total). Preceding
      exposure, immediately post-exposure, 1 hour and 2 hours post-exposure, FMD, blood
      pressure and plasma endothelin-1 and NOx concentrations were measured. Data were
      analyzed using repeated-measures ANOVA and linear mixed model. RESULTS: Following
      exercise in DE, plasma NOx significantly increased and was significantly greater
      than FA (p<0.05). Two hours following DE exposure, endothelin-1 was significantly
      less than FA (p = 0.037) but exercise intensity did not modify this response. DE
      exposure did not affect FMD or blood pressure. CONCLUSION: Our results suggest
      that exercising in DE did not adversely affect plasma NOX, endothelin-1, FMD and
      blood pressure. Therefore, recommendations for healthy individuals to moderate or
      avoid exercise during bouts of high pollution appear to have no acute protective
      effect.

PMID- 29466395
TI  - Dynamics of monocytic HLA-DR expression differs between bacterial etiologies
      during the course of bloodstream infection.
AB  - OBJECTIVE: In the pathogenesis of sepsis, activation of both pro- and anti
      inflammatory responses are key components, but knowledge is lacking on the
      association between bacterial etiology and development of dysregulated responses
      with sustained immunosuppression. The aim of this study was to evaluate how the
      immunosupression marker HLA-DR on monocytes (mHLA-DR) is associated with
      bacterial etiology and markers of inflammation during the clinical trajectory of
      bloodstream infection (BSI). METHODS: Ninety-one adults, predominantly non-ICU
      patients, with BSI caused by Streptococcus pneumoniae (n = 27), Staphylococcus
      aureus (n = 22), Escherichia coli/Klebsiella pneumoniae (n = 23), and other
      species (n = 19) were prospectively included, and sampled on admission (day 0)
      and on days 1-2, 3, 7+/-1, 14+/-2, and 28+/-4. RESULTS: The dynamics of mHLA-DR,
      measured by flow cytometry, differed significantly between etiology groups
      (p<0.001). Patients with S. pneumoniae and S. aureus BSI demonstrated low initial
      mHLA-DR, with the S. aureus group showing delayed recovery over time. Eleven
      patients (55% S. aureus) had negative outcome (secondary bacteremia or death) and
      they demonstrated sustained C-reactive protein elevation, neutrophilia,
      lymphocytopenia, and loss of mHLA-DR. CONCLUSIONS: Dynamics of mHLA-DR varied
      according to the bacterial etiology of infection, with delayed recovery in
      patients with S. aureus BSI. Patients with negative outcome showed sustained CRP
      elevation, neutrophilia, lymphocytopenia, and low levels of mHLA-DR, supporting
      the theory of a dysregulated host response with persistent inflammation and
      immunosuppression in late stages of deleterious sepsis.

PMID- 29466396
TI  - Hydrogen sulfide is expressed in the human and the rat cultured nucleus pulposus
      cells and suppresses apoptosis induced by hypoxia.
AB  - Apoptosis plays pivotal role in the pathogenesis of degenerative disc diseases,
      which is the primary contributor to low back pain. Although the role of hydrogen
      sulfide (H2S) in cell apoptosis is well appreciated, the effects and mechanism
      that H2S regulates the program death of intervertebral disc cell are not yet
      elucidated. In this study, we utilized the nucleus pulposus (NP) from patients
      with lumbar disc herniation to investigate the relationship between endogenous
      H2S and NP cells apoptosis in human. Furthermore, we analyzed primary rat NP
      cells to study the effects of exogenous H2S on hypoxia induced cell apoptosis.
      Human NP samples were obtained from patients with lumbar disc herniation and were
      divided into uncontained and contained herniation groups. Using
      immunohistochemistry staining and sulphur-sensitive electrode, we detected the
      expression of cystathionine-beta-synthase (CBS) and cystathionine gamma-lyase
      (CSE), as well as the production of endogenous H2S in human NP. Tunel staining
      showed increased apoptosis in NP from herniated disc; and there was significant
      correlation between H2S generation and apoptosis in human NP. CoCl2 was then used
      to induce hypoxia in cultured primary rat NP cells. Annexin V staining indicated
      that exogenous NaHS attenuated hypoxia induced apoptosis in rat NP cells.
      Furthermore, hypoxia significantly increased the levels of multiple apoptosis
      associated proteins (Fas, Cytochromes C, Caspase 9 and cleaved-Caspase-3) in
      cells, which were eliminated by NaHS. Our study demonstrates the presence of
      endogenous H2S in human intervertebral disc; and the endogenous H2S generation
      rate is associated with NP apoptosis in herniated disc. In vitro study showes
      exogenous H2S donor attenuates hypoxia induced apoptosis in primary rat NP cells.
      Thus, our work provides insights that H2S may have beneficial effects in treating
      degenerative disc diseases.

PMID- 29466397
TI  - A new disclosure index for Non-Governmental Organizations.
AB  - Website of Non-governmental organization (NGO) is a focal medium of sharing
      information in response to transparency demands and addressing trust deficits
      between stakeholders. Many researchers have proposed accountability approaches to
      measure information sharing trends through websites. This article discusses a new
      index to measure online disclosure trends along with the theoretical properties
      of the index and a practical application of data from NGOs working in Pakistan.
      The websites have been coded in 2016. Results show that NGOs with branch offices
      have better disclosure scores than single-office NGOs, and international NGOs
      score better than local NGOs. NGOs that are more often the subject of newspaper
      reports have better disclosure trends.

PMID- 29466398
TI  - Complex genetic patterns in human arise from a simple range-expansion model over
      continental landmasses.
AB  - Although it is generally accepted that geography is a major factor shaping human
      genetic differentiation, it is still disputed how much of this differentiation is
      a result of a simple process of isolation-by-distance, and if there are factors
      generating distinct clusters of genetic similarity. We address this question
      using a geographically explicit simulation framework coupled with an Approximate
      Bayesian Computation approach. Based on six simple summary statistics only, we
      estimated the most probable demographic parameters that shaped modern human
      evolution under an isolation by distance scenario, and found these were the
      following: an initial population in East Africa spread and grew from 4000
      individuals to 5.7 million in about 132 000 years. Subsequent simulations with
      these estimates followed by cluster analyses produced results nearly identical to
      those obtained in real data. Thus, a simple diffusion model from East Africa
      explains a large portion of the genetic diversity patterns observed in modern
      humans. We argue that a model of isolation by distance along the continental
      landmasses might be the relevant null model to use when investigating selective
      effects in humans and probably many other species.

PMID- 29466399
TI  - Acute basilar thrombosis: Recanalization following intravenous thrombolysis is
      dependent on thrombus length.
AB  - INTRODUCTION: We investigated whether thrombus length measured in Computed
      Tomography Angiography (CTA) is predictive of the success rate of intravenous
      thrombolysis (IVT) in acute basilar occlusion and whether recanalization can be
      achieved by additional mechanical endovascular thrombectomy. METHODS: In 51
      patients with acute basilar thrombosis thrombus length was measured on CTA images
      before intravenous thrombolysis (IVT) with rt-PA was started. After 114 minutes
      on average success of IVT was evaluated either by CTA or DSA. Patients with
      persistent basilar occlusion and no major brainstem infarction on CT underwent
      endovascular recanalization. RESULTS: 87% of patients had no recanalization of
      basilar artery after IVT alone. The average thrombus length was 15 mm in patients
      with persistent basilar occlusion after IVT and 7 mm in patients with
      recanalization after IVT. Thrombi longer than 13 mm did not resolve after IVT
      alone and 80% of thrombi shorter than 13 mm did not resolve either. 41 patients
      were transferred to endovascular recanalization; endovascular therapy was
      performed successfully in 90% (37 / 41). CONCLUSIONS: Recanalization rates in
      acute basilar occlusion after IVT alone are low and dependent on thrombus length.
      Additional mechanical endovascular thrombectomy showed to be a very successful
      recanalization therapy.

PMID- 29466400
TI  - Insights into the origin of the high variability of multivalent-meiotic
      associations in holocentric chromosomes of Tityus (Archaeotityus) scorpions.
AB  - Scorpions represent an intriguing group of animals characterized by a high
      incidence of heterozygous chromosomal rearrangements. In this work, we examined
      six species of Tityus (Archaeotityus) from Brazilian fauna with a particular
      focus on elucidating the rearrangements responsible for the intraspecific
      variability of diploid number and the presence of long chromosomal chains in
      meiosis. To access any interpopulation diversity, we also studied individuals
      from four species representing distinct localities. Most species demonstrated
      intraspecific polymorphism in diploid number (2n = 19 and 2n = 20 in T.
      clathratus, T. mattogrossensis, and T. pusillus, 2n = 16, 2n = 17 and 2n = 18 in
      T. paraguayensis, and 2n = 16 and 2n = 24 in T. silvestris) and multi-chromosomal
      associations during meiosis I, which differed even among individuals with the
      same chromosome number. In some species, the heterozygous rearrangements were not
      fixed, resulting such as in Tityus clathatrus, in 11 different chromosomal
      configurations recognized within a same population. Based on meiotic chromosome
      behaviour, we suggested that independent rearrangements (fusion/fission and
      reciprocal translocations), occurring in different combinations, originated the
      multi-chromosomal chains. To evaluate the effects of these chromosome chains on
      meiotic segregation, we applied the chi-square test in metaphase II cells. The
      non-significant occurrence of aneuploid nuclei indicated that non-disjunction was
      negligible in specimens bearing heterozygous rearrangements. Finally, based on
      our analysis of many chromosome characteristics, e.g., holocentricity, achiasmate
      meiosis, endopolyploidy, ability to segregate heterosynaptic or unsynapsed
      chromosomes, (TTAGG)n sequence located in terminal regions of rearranged
      chromosomes, we suggest that the maintenance of multi-chromosomal associations
      may be evolutionarily advantageous for these species.

PMID- 29466401
TI  - Assessing the potential impacts of a changing climate on the distribution of a
      rabies virus vector.
AB  - Common vampire bats (Desmodus rotundus) occur throughout much of South America to
      northern Mexico. Vampire bats have not been documented in recent history in the
      United States, but have been documented within about 50 km of the U.S. state of
      Texas. Vampire bats feed regularly on the blood of mammals and can transmit
      rabies virus to native species and livestock, causing impacts on the health of
      prey. Thus cattle producers, wildlife management agencies, and other stakeholders
      have expressed concerns about whether vampire bats might spread into the southern
      United States. On the other hand, concerns about vampire-borne rabies can also
      result in wanton destruction at bat roosts in areas occupied by vampire bats, but
      also in areas not known to be occupied by this species. This can in turn
      negatively affect some bat roosts, populations, and species that are of
      conservation concern, including vampire bats. To better understand the current
      and possible future distribution of vampire bats in North America and help
      mitigate future cattle management problems, we used 7,094 vampire bat occurrence
      records from North America and species distribution modeling (SDM) to map the
      potential distribution of vampire bats in North America under current and future
      climate change scenarios. We analysed and mapped the potential distribution of
      this species using 5 approaches to species distribution modeling: logistic
      regression, multivariate adaptive regression splines, boosted regression trees,
      random forest, and maximum entropy. We then projected these models into 17 "worst
      case" future climate scenarios for year 2070 to generate hypotheses about how the
      vampire bat distribution in North America might change in the future. Of the
      variables used in this analysis, minimum temperature of the coldest month had the
      highest variable importance using all 5 SDM approaches. These results suggest two
      potential near-future routes of vampire bat dispersal into the U.S., one via
      southern Texas, and a second into southern Florida. Some of our SDM models
      support the hypothesis that suitable habitat for vampire bats may currently exist
      in parts of the Mexico-U.S. borderlands, including extreme southern portions of
      Texas, as well as in southern Florida. However, this analysis also suggests that
      extensive expansion into the south-eastern and south-western U.S. over the coming
      ~60 years appears unlikely.

PMID- 29466402
TI  - The effect of varying levels of vehicle automation on drivers' lane changing
      behaviour.
AB  - Much of the Human Factors research into vehicle automation has focused on driver
      responses to critical scenarios where a crash might occur. However, there is less
      knowledge about the effects of vehicle automation on drivers' behaviour during
      non-critical take-over situations, such as driver-initiated lane-changing or
      overtaking. The current driving simulator study, conducted as part of the EC
      funded AdaptIVe project, addresses this issue. It uses a within-subjects design
      to compare drivers' lane-changing behaviour in conventional manual driving,
      partially automated driving (PAD) and conditionally automated driving (CAD). In
      PAD, drivers were required to re-take control from an automated driving system in
      order to overtake a slow moving vehicle, while in CAD, the driver used the
      indicator lever to initiate a system-performed overtaking manoeuvre. Results
      showed that while drivers' acceptance of both the PAD and CAD systems was high,
      they generally preferred CAD. A comparison of overtaking positions showed that
      drivers initiated overtaking manoeuvres slightly later in PAD than in manual
      driving or CAD. In addition, when compared to conventional driving, drivers had
      higher deviations in lane positioning and speed, along with higher lateral
      accelerations during lane changes following PAD. These results indicate that even
      in situations which are not time-critical, drivers' vehicle control after
      automation is degraded compared to conventional driving.

PMID- 29466403
TI  - Estimating the burden of rabies in Ethiopia by tracing dog bite victims.
AB  - In developing countries where financial resources are limited and numerous
      interests compete, there is a need for quantitative data on the public health
      burden and costs of diseases to support intervention prioritization. This study
      aimed at estimating the health burden and post-exposure treatment (PET) costs of
      canine rabies in Ethiopia by an investigation of exposed human cases. Data on
      registered animal bite victims during the period of one year were collected from
      health centers in three districts, i.e. Bishoftu, Lemuna-bilbilo and Yabelo, to
      account for variation in urban highland and lowland areas. This data collection
      was followed by an extensive case search for unregistered victims in the same
      districts as the registered cases. Victims were visited and questioned on their
      use of PET, incurred treatment costs and the behavioral manifestations of the
      animal that had bitten them. Based on the collected data PET costs were evaluated
      by financial accounting and the health burden was estimated in Disability
      Adjusted Life Years (DALYs). In total 655 animal bite cases were traced of which
      96.5% was caused by dog bites. 73.6% of the biting dogs were suspected to be
      potentially rabid dog. Annual suspected rabid dog exposures were estimated per
      evaluated urban, rural highland and rural lowland district at, respectively, 135,
      101 and 86 bites, which led, respectively, to about 1, 4 and 3 deaths per 100,000
      population. In the same district order average costs per completed PET equaled to
      23, 31 and 40 USD, which was significantly higher in rural districts.
      Extrapolation of the district results to the national level indicated an annual
      estimate of approximately 3,000 human deaths resulting in about 194,000 DALYs per
      year and 97,000 exposed persons requiring on average 2 million USD treatment
      costs per year countrywide. These estimations of the burden of rabies to the
      Ethiopian society provide decision makers insights into the potential benefits of
      implementing effective interventions.

PMID- 29466404
TI  - Antioxidant genes of plants and fungal pathogens are distinctly regulated during
      disease development in different Rhizoctonia solani pathosystems.
AB  - Biotic stress, as a result of plant-pathogen interactions, induces the
      accumulation of reactive oxygen species in the cells, causing severe oxidative
      damage to plants and pathogens. To overcome this damage, both the host and
      pathogen have developed antioxidant systems to quench excess ROS and keep ROS
      production and scavenging systems under control. Data on ROS-scavenging systems
      in the necrotrophic plant pathogen Rhizoctonia solani are just emerging. We
      formerly identified vitamin B6 biosynthetic machinery of R. solani AG3 as a
      powerful antioxidant exhibiting a high ability to quench ROS, similar to CATALASE
      (CAT) and GLUTATHIONE S-TRANSFERASE (GST). Here, we provide evidence on the
      involvement of R. solani vitamin B6 biosynthetic pathway genes; RsolPDX1
      (KF620111.1), RsolPDX2 (KF620112.1), and RsolPLR (KJ395592.1) in vitamin B6 de
      novo biosynthesis by yeast complementation assays. Since gene expression studies
      focusing on oxidative stress responses of both the plant and the pathogen
      following R. solani infection are very limited, this study is the first
      coexpression analysis of genes encoding vitamin B6, CAT and GST in plant and
      fungal tissues of three pathosystems during interaction of different AG groups of
      R. solani with their respective hosts. The findings indicate that distinct
      expression patterns of fungal and host antioxidant genes were correlated in
      necrotic tissues and their surrounding areas in each of the three R. solani
      pathosystems: potato sprout-R. solani AG3; soybean hypocotyl-R. solani AG4 and
      soybean leaves-R. solani AG1-IA interactions. Levels of ROS increased in all
      types of potato and soybean tissues, and in fungal hyphae following infection of
      R. solani AGs as determined by non-fluorescence and fluorescence methods using
      H2DCF-DA and DAB, respectively. Overall, we demonstrate that the co-expression
      and accumulation of certain plant and pathogen ROS-antioxidant related genes in
      each pathosystem are highlighted and might be critical during disease development
      from the plant's point of view, and in pathogenicity and developing of infection
      structures from the fungal point of view.

PMID- 29466405
TI  - Molecular phylogeny of Panicum s. str. (Poaceae, Panicoideae, Paniceae) and
      insights into its biogeography and evolution.
AB  - Panicum sensu stricto is a genus of grasses (Poaceae) with nearly, according to
      this study, 163 species distributed worldwide. This genus is included in the
      subtribe Panicinae together with Louisiella, the latter with 2 species. Panicum
      and subtribe Panicinae are characterized by including annual or perennial taxa
      with open and lax panicles, and spikelets with the lower glume reduced; all taxa
      also share a basic chromosome number of x = 9 and a Kranz leaf blade anatomy
      typical of the NAD-me subtype photosynthetic pathway. Nevertheless, the
      phylogenetic placements of many Panicum species, and the circumscription of the
      genus, remained untested. Therefore, phylogenetic analyses were conducted using
      sequence data from the ndhF plastid region, in an extensive worldwide sampling of
      Panicum and related genera, in order to infer evolutionary relationships and to
      provide a phylogenetic framework to review the classification of the genus.
      Diversification times, historical biogeography and evolutionary patterns of the
      life history (annual vs. perennial) in the subtribe and Panicum were also
      studied. Results obtained provide strong support for a monophyletic Panicum
      including 71 species and 7 sections, of which sections Arthragrostis and Yakirra
      are new in the genus; 7 new combinations are made here. Furthermore, 32 species
      traditionally assigned to Panicum were excluded from the genus, and discussed in
      other subtribes of Paniceae. Our study suggested that early diversification in
      subtribe Panicinae and Panicum occurred through the Early-Mid Miocene in the
      Neotropics, while the subsequent diversification of its sections mainly occurred
      in the Late Miocene-Pleistocene, involving multiple dispersals to all continents.
      Our analyses also showed that transition rates and changes between annual and
      perennial life history in Panicum were quite frequent, suggesting considerable
      lability of this trait. Changes of the life history, together with C4
      photosynthesis, and the multiple dispersal events since the Mid Miocene, seem to
      have facilitated a widespread distribution of the genus. All these findings
      contribute to a better understanding of the systematics and evolution of Panicum.

PMID- 29466406
TI  - Increased fecal calprotectin levels in Crohn's disease correlate with elevated
      serum Th1- and Th17-associated cytokines.
AB  - BACKGROUND: Patient-reported symptoms and endoscopic disease activity do not
      correlate well in Crohn's disease (CD). This warrants the need for reliable
      biomarkers to early detect active intestinal inflammation. Currently, the fecal
      calprotectin level is the most commonly used biomarker for inflammatory activity
      in CD. However, the diagnostic accuracy of the fecal calprotectin level is not
      fully efficacious and diagnosis may be further improved by the identification of
      other biomarkers for active CD. Here, we studied the association of a variety of
      serum disease markers with fecal calprotectin levels in CD patients. METHODS: 39
      CD patients were included and subdivided into 'normal' (defined as < 200 mg/kg
      feces) and 'increased' (defined as > 200 mg/kg feces) fecal calprotectin level
      groups. Serum levels of 37 different cytokines, chemokines and markers for
      angiogenesis and vascular injury were quantified by an electrochemiluminescence
      multiplex assay (V-PLEX Human Biomarker 40-Plex Kit of Meso Scale Discovery (r)).
      Correlations between individual biomarkers and the fecal calprotectin level were
      assessed using Spearman's correlation coefficient (rho). RESULTS: A highly
      significant positive correlation was observed between the pro-inflammatory serum
      cytokines IFN-gamma and CRP and fecal calprotectin levels (P < 0.01). Moreover,
      fecal calprotectin levels showed a significant positive correlation with IL-6,
      TNF-beta, SAA and IL-17A (P < 0.05). CONCLUSION: We show that a positive
      correlation exists between multiple serum Th1- and Th17-associated cytokines and
      the fecal calprotectin level. These cytokines and CRP may serve as additional
      biomarkers for determining disease activity and evaluating treatment response in
      CD. Ultimately, this may result in more efficient treatment of active disease in
      CD patients and prevention of complications.

PMID- 29466407
TI  - A scale assessing doctor-patient communication in a context of acute conditions
      based on a systematic review.
AB  - BACKGROUND: There is no validated generic tool to measure Doctor-Patient
      Communication (DPC) in a context of acute conditions. OBJECTIVE: To create and
      validate such a scale in a real population. MATERIALS AND METHOD: We performed a
      systematic review of validated DPC scales available in English. From these, using
      a theoretical model based on a multidisciplinary approach, we selected pertinent
      items that met the inclusion criteria and included them in a simple
      questionnaire. This tool based on a synthesis of the literature was then
      validated in a prospective study in two hospital emergency departments. RESULTS:
      We found 22 pertinent questionnaires and scoring systems. From these, we
      extracted items and built a scale based on 15 questions with graded responses
      (Likert from 1 to 4). The mean time for questionnaire completion was 3 minutes.
      We included 189 adults and adolescents in the study and analyzed complete
      responses to the questionnaire by 149 patients, gathered over the phone one week
      after their consultation. The scale had high internal consistency (Cronbach's
      alpha = 0.89) and good external validity. Two questions were removed due to
      redundancy giving a scale based on 13 questions. CONCLUSIONS: We have created an
      easy-to-use and validated generic questionnaire to assess DPC in a context of
      acute conditions, usable both in clinical research and in routine practice.

PMID- 29466408
TI  - The clinical characteristics of adults with rheumatic heart disease in Yangon,
      Myanmar: An observational study.
AB  - BACKGROUND: Rheumatic heart disease (RHD) is a major cause of premature death in
      low and middle-income countries. The greatest barrier to RHD control is neglect
      of the disease in national health policies and a lack of prevalence data that
      might inform control efforts. Myanmar is making remarkable progress against many
      infectious diseases, but there are almost no data to define the clinical burden
      of RHD in the country. This prospective audit was performed in an adult medical
      ward of a tertiary-referral hospital in Yangon, to gain an insight into the
      prevalence of RHD in Myanmar. PRINCIPAL FINDINGS: All patients admitted to the
      ward between May 1, 2016 and April 30, 2017 were eligible for enrolment. RHD was
      confirmed in 96 patients who were admitted on 134 occasions, representing 1.1% of
      the 12,172 adult medical admissions during the study period. This compared with
      410 (3.4%) admissions with HIV and 14 (0.1%) with malaria. Patients with RHD had
      a median age of 44 years (interquartile range: 35-59); 70 (73%) were female. Only
      one patient had ever had surgery despite 79 (82%) meeting criteria for
      intervention; 54 (56%) patients were not receiving any regular clinician review.
      Prior to hospitalisation only 18 (19%) patients were receiving regular
      penicillin. Only 8 (19%) of the 42 women <50 years were using contraception. Of
      49 patients who had been hospitalised previously, 22 (45%) were receiving no
      regular therapy. During the study three (3.1%) patients died, and 28 (29%) were
      lost to follow-up. Of the 65 (68%) alive and retained in care, 21 (32%) were
      still experiencing moderate-severe RHD-related symptoms at the study's end.
      CONCLUSIONS: There is a significant and unmet clinical burden of RHD in Myanmar.
      A national RHD programme would improve patient care, reducing morbidity and
      mortality from this preventable disease.

PMID- 29466409
TI  - IL-7 treatment augments and prolongs sepsis-induced expansion of IL-10-producing
      B lymphocytes and myeloid-derived suppressor cells.
AB  - Immunological dysregulation in sepsis is associated with often lethal secondary
      infections. Loss of effector cells and an expansion of immunoregulatory cell
      populations both contribute to sepsis-induced immunosuppression. The extent and
      duration of this immunosuppression are unknown. Interleukin 7 (IL-7) is important
      for the maintenance of lymphocytes and can accelerate the reconstitution of
      effector lymphocytes in sepsis. How IL-7 influences immunosuppressive cell
      populations is unknown. We have used the mouse model of peritoneal contamination
      and infection (PCI) to investigate the expansion of immunoregulatory cells as
      long-term sequelae of sepsis with or without IL-7 treatment. We analysed the
      frequencies and numbers of regulatory T cells (Tregs), double negative T cells,
      IL-10 producing B cells and myeloid-derived suppressor cells (MDSCs) for 3.5
      months after sepsis induction. Sepsis induced an increase in IL-10+ B cells,
      which was enhanced and prolonged by IL-7 treatment. An increased frequency of
      MDSCs in the spleen was still detectable 3.5 months after sepsis induction and
      this was more pronounced in IL-7-treated mice. MDSCs from septic mice were more
      potent at suppressing T cell proliferation than MDSCs from control mice. Our data
      reveal that sepsis induces a long lasting increase in IL-10+ B cells and MDSCs.
      Late-onset IL-7 treatment augments this increase, which should be relevant for
      clinical interventions.

PMID- 29466410
TI  - Familial patterning and prevalence of male androphilia among Istmo Zapotec men
      and muxes.
AB  - Male androphilia (i.e., male sexual attraction to other adult males) is known to
      cluster within families. Some studies demonstrate that male androphilia clusters
      in both the paternal and maternal familial lines, whereas other studies
      demonstrated that it clusters only in the latter. Most of these studies were
      conducted in Euro-American populations where fertility is low and the sexual
      orientation of male relatives can sometimes be difficult to ascertain. These two
      factors can potentially confound the results of such studies. To address these
      limitations, we examined the familial patterning of male androphilia among the
      Istmo Zapotec of Oaxaca, Mexico--a high fertility, non-Euro-American population
      where androphilic males are known locally as muxes, a third gender category. The
      Istmo Zapotec recognize two types of muxes--muxe gunaa and muxe nguiiu--who
      typify the transgender and cisgender forms of male androphilia, respectively. We
      compared the familial patterning of male androphilia between muxe gunaa and muxe
      nguiiu, as well as between gynephilic men and muxes (both cisgender and
      transgender forms combined). Istmo Zapotec muxe gunaa and muxe nguiiu exhibit
      similar familial patterning of male androphilia. Overall, muxes were
      characterized by significantly more muxe relatives than gynephilic men. This
      familial patterning was equivalent in both the paternal and maternal lines of
      muxes. The population prevalence rate of male androphilia was estimated to fall
      between 3.37-6.02% in the Istmo Zapotec. This is the first study that has
      compared cisgender and transgender androphilic males from the same high fertility
      population and demonstrated that the two do not differ with respect to the
      familial patterning of male androphilia.

PMID- 29466411
TI  - Molecular epidemiology of tuberculosis in Tasmania and genomic characterisation
      of its first known multi-drug resistant case.
AB  - BACKGROUND: The origin and spread of tuberculosis (TB) in Tasmania and the types
      of strains of Mycobacterium tuberculosis complex (MTBC) present in the population
      are largely unknown. OBJECTIVE: The aim of this study was to perform the first
      genomic analysis of MTBC isolates from Tasmania to better understand the
      epidemiology of TB in the state. METHODS: Whole-genome sequencing was performed
      on cultured isolates of MTBC collected from 2014-2016. Single-locus variant
      analysis was applied to determine the phylogeny of the isolates and the presence
      of drug-resistance mutations. The genomic data were then cross-referenced against
      public health surveillance records on each of the cases. RESULTS: We determined
      that 83.3% of TB cases in Tasmania from 2014-2016 occurred in non-Australian born
      individuals. Two possible TB clusters were identified based on single locus
      variant analysis, one from November-December 2014 (n = 2), with the second from
      May-August 2015 (n = 4). We report here the first known isolate of multi-drug
      resistant (MDR) M. tuberculosis in Tasmania from 2016 for which we established
      its drug resistance mutations and potential overseas origin. In addition, we
      characterised a case of M. bovis TB in a Tasmanian-born person who presented in
      2014, approximately 40 years after the last confirmed case in the state's bovids.
      CONCLUSIONS: TB in Tasmania is predominantly of overseas origin with
      genotypically-unique drug-susceptible isolates of M. tuberculosis. However, the
      state also exhibits features of TB that are observed in other jurisdictions,
      namely, the clustering of cases, and drug resistance. Early detection of TB and
      contact tracing, particularly of overseas-born cases, coordinated with rapid
      laboratory drug-susceptibility testing and molecular typing, will be essential
      for Tasmania to reach the World Health Organisation's TB eradication goals for
      low-incidence settings.

PMID- 29466412
TI  - Determinants of satisfaction with cosmetic outcome in breast cancer survivors: A
      cross-sectional study.
AB  - Little research has been done into cosmetic outcomes in non-Western breast cancer
      populations. We aimed to study the prevalence and determinants of dissatisfaction
      with cosmetic outcome after breast cancer surgery of Asian breast cancer
      survivors, and its association with patient-reported anxiety, depression, and
      quality of life. In a hospital-based cross-sectional study, 384 breast cancer
      survivors of at least 12 months after diagnosis completed questionnaires on
      satisfaction with cosmetic appearance, quality of life (EORTC-QLQ-C30) and
      anxiety and depression (HADS). Cumulative logit models were used to examine the
      adjusted association between dissatisfaction with cosmetic appearance and
      demographic and clinical characteristics. Kruskal-Wallis test was used to test
      for associations between dissatisfaction with cosmetic appearance and patient
      reported outcomes. Overall, 20% of women reported to be (very) dissatisfied with
      cosmetic appearance. Survivors of Chinese ethnicity were more likely dissatisfied
      with cosmetic appearance compared to Malay survivors (22% and 14% respectively,
      adjusted OR = 2.4, 95%CI: 1.4-3.9). Women with DCIS (adjusted OR = 2.2, 95%CI:
      1.3-3.7) or advanced stage disease (adjusted OR = 2.2, 95%CI: 1.2-3.9) had a
      higher risk of being dissatisfied with their cosmetic appearance. Women treated
      with mastectomy were at a higher risk of dissatisfaction with cosmetic appearance
      (adjusted OR = 1.7, 95%CI: 1.1-2.5). Dissatisfaction with cosmetic appearance was
      associated with increased depression scores. In this South-East Asian population,
      one in five breast cancer patients were (very) dissatisfied with the cosmetic
      outcome of treatment. Chinese women, women with larger tumors and women treated
      with mastectomy were most likely to report dissatisfaction with cosmetic
      appearance.

PMID- 29466413
TI  - Impact of insulin on primary arcuate neurons culture is dependent on early
      postnatal nutritional status and neuronal subpopulation.
AB  - Nutrition plays a critical role in programming and shaping linear growth during
      early postnatal life through direct action on the development of the
      neuroendocrine somatotropic (GH/IGF-1) axis. IGF-1 is a key factor in modulating
      the programming of linear growth during this period. Notably, IGF-1
      preferentially stimulates axonal growth of GHRH neurons in the arcuate nucleus of
      the hypothalamus (Arc), which is crucial for the proliferation of somatotroph
      progenitors in the pituitary, thus influencing later GH secretory capacity.
      However, other nutrition-related hormones may also be involved. Among them,
      insulin shares several structural and functional similarities with IGF-1, as well
      as downstream signaling effectors. We investigated the role of insulin in the
      control of Arc axonal growth using an in vitro model of arcuate explants culture
      and a cell-type specific approach (GHRH-eGFP mice) under both physiological
      conditions (normally fed pups) and those of dietary restriction (underfed pups).
      Our data suggest that insulin failed to directly control axonal growth of Arc
      neurons or influence specific IGF-1-mediated effects on GHRH neurons. Insulin may
      act on neuronal welfare, which appears to be dependent on neuronal sub
      populations and is influenced by the nutritional status of pups in which Arc
      neurons develop.

PMID- 29466414
TI  - Assessing the capability to experience a 'good death': A qualitative study to
      directly elicit expert views on a new supportive care measure grounded in Sen's
      capability approach.
AB  - BACKGROUND: Sen's capability approach is underspecified; one decision left to
      those operationalising the approach is how to identify sets of relevant and
      important capabilities. Sen has suggested that lists be developed for specific
      policy or research objectives through a process of public reasoning and
      discussion. Robeyns offers further guidance in support of Sen's position,
      suggesting that lists should be explicit, discussed and defended; methods be
      openly scrutinised; lists be considered both in terms of what is ideal and what
      is practical ('generality'); and that lists be exhaustive. Here, the principles
      suggested by Robeyns are operationalised to facilitate external scrutiny of a
      list of capabilities identified for use in the evaluation of supportive end of
      life care. METHODS: This work started with an existing list of seven capabilities
      (the ICECAP-SCM), identified as being necessary for a person to experience a good
      death. Semi-structured qualitative interviews were conducted with 20 experts in
      economics, psychology, ethics and palliative care, to facilitate external
      scrutiny of the developed list. Interviews were recorded, transcribed and
      analysed using constant comparison. RESULTS: The seven capabilities were found to
      encompass concepts identified as important by expert stakeholders (to be
      exhaustive) and the measure was considered feasible for use with patients
      receiving care at the end of life. CONCLUSION: The rigorous development of lists
      of capabilities using both initial participatory approaches with affected
      population groups, and subsequent assessment by experts, strengthens their
      democratic basis and may encourage their use in policy contexts.

PMID- 29466415
TI  - Revisiting policy on chronic HCV treatment under the Thai Universal Health
      Coverage: An economic evaluation and budget impact analysis.
AB  - Thailand is encountering challenges to introduce the high-cost sofosbuvir for
      chronic hepatitis C treatment as part of the Universal Health Care's benefit
      package. This study was conducted in respond to policy demand from the Thai
      government to assess the value for money and budget impact of introducing
      sofosbuvir-based regimens in the tax-based health insurance scheme. The Markov
      model was constructed to assess costs and benefits of the four treatment options
      that include: (i) current practice-peginterferon alfa (PEG) and ribavirin (RBV)
      for 24 weeks in genotype 3 and 48 weeks for other genotypes; (ii) Sofosbuvir plus
      peginterferon alfa and ribavirin (SOF+PEG-RBV) for 12 weeks; (iii) Sofosbuvir and
      daclatasvir (SOF+DCV) for 12 weeks; (iv) Sofosbuvir and ledipasvir (SOF+LDV) for
      12 weeks for non-3 genotypes and SOF+PEG-RBV for 12 weeks for genotype 3
      infection. Given that policy options (ii) and (iii) are for pan-genotypic
      infection, the cost of genotype testing was applied only for policy options (i)
      and (iv). Results reveal that all sofosbuvir-based regimens had greater quality
      adjusted life years (QALY) gains compared with the current treatment, therefore
      associated with lower lifetime costs and more favourable health outcomes.
      Additionally, among the three regimens of sofosbuvir, SOF+PEG-RBV for genotype 3
      and SOF+LDV for non-3 genotype are the most cost-effective treatment option with
      the threshold of 160,000 THB per QALY gained. The results of this study had been
      used in policy discussion which resulted in the recent inclusion of SOF+PEG-RBV
      for genotype 3 and SOF+LDV for non-3 genotype in the Thailand's benefit package.

PMID- 29466416
TI  - Elevated visual dependency in young adults after chemotherapy in childhood.
AB  - Chemotherapy in childhood can result in long-term neurophysiological side
      effects, which could extend to visual processing, specifically the degree to
      which a person relies on vision to determine vertical and horizontal (visual
      dependency). We investigated whether adults treated with chemotherapy in
      childhood experience elevated visual dependency compared to controls and whether
      any difference is associated with the age at which subjects were treated. Visual
      dependency was measured in 23 subjects (mean age 25.3 years) treated in childhood
      with chemotherapy (CTS) for malignant, solid, non-CNS tumors. We also stratified
      CTS into two groups: those treated before 12 years of age and those treated from
      12 years of age and older. Results were compared to 25 healthy, age-matched
      controls. The subjective visual horizontal (SVH) and vertical (SVV) orientations
      was recorded by having subjects position an illuminated rod to their perceived
      horizontal and vertical with and without a surrounding frame tilted clockwise and
      counter-clockwise 20 degrees  from vertical. There was no significant difference
      in rod accuracy between any CTS groups and controls without a frame. However,
      when assessing visual dependency using a frame, CTS in general (p = 0.006) and
      especially CTS treated before 12 years of age (p = 0.001) tilted the rod
      significantly further in the direction of the frame compared to controls. Our
      findings suggest that chemotherapy treatment before 12 years of age is associated
      with elevated visual dependency compared to controls, implying a visual bias
      during spatial activities. Clinicians should be aware of symptoms such as visual
      vertigo in adults treated with chemotherapy in childhood.

PMID- 29466417
TI  - Epinephrine modulates Na+/K+ ATPase activity in Caco-2 cells via Src, p38MAPK,
      ERK and PGE2.
AB  - Epinephrine, a key stress hormone, is known to affect ion transport in the colon.
      Stress has been associated with alterations in colonic functions leading to
      changes in water movements manifested as diarrhea or constipation. Colonic water
      movement is driven by the Na+-gradient created by the Na+/K+-ATPase. Whether
      epinephrine acts via an effect on the Na+/K+-ATPase hasn't been studied before.
      The aim of this work was to investigate the effect of epinephrine on the Na+/K+
      ATPase and to elucidate the signaling pathway involved using CaCo-2 cells as a
      model. The activity of the Na+/K+-ATPase was assayed by measuring the amount of
      inorganic phosphate released in presence and absence of ouabain, a specific
      inhibitor of the enzyme. Epinephrine, added for 20 minutes, decreased the
      activity of the Na+/K+-ATPase by around 50%. This effect was found to be mediated
      by alpha2 adrenergic receptors as it was fully abolished in the presence of
      yohimbine an alpha2-blocker, but persisted in presence of other adrenergic
      antagonists. Furthermore, treatment with Rp-cAMP, a PKA inhibitor, mimicked
      epinephrine's negative effect and didn't result in any additional inhibition when
      both were added simultaneously. Treatment with indomethacin, PP2, SB202190, and
      PD98059, respective inhibitors of COX enzymes, Src, p38MAPK, and ERK completely
      abrogated the effect of epinephrine. The effect of epinephrine did not appear
      also in presence of inhibitors of all four different types of PGE2 receptors.
      Western blot analysis revealed an epinephrine-induced increase in the
      phosphorylation of p38 MAPK and ERK that disappeared in presence of respectively
      PP2 and SB2020190. In addition, an inhibitory effect, similar to that of
      epinephrine's, was observed upon incubation with PGE2. It was concluded that
      epinephrine inhibits the Na+/K+-ATPase by the sequential activation of alpha2
      adrenergic receptors, Src, p38MAPK, and ERK leading to PGE2 release.

PMID- 29466418
TI  - Evaluation of the biocontrol efficacy of a Serratia marcescens strain indigenous
      to tea rhizosphere for the management of root rot disease in tea.
AB  - The aim of the present study is to evaluate plant growth promoting and biocontrol
      efficacy of a Serratia marcescens strain ETR17 isolated from tea rhizosphere for
      the effective management of root rot disease in tea. Isolated bacterial culture
      ETR17 showed significant level of in vitro antagonism against nine different
      foliar and root pathogens of tea. The phenotypic and molecular characterization
      of ETR17 revealed the identity of the bacterium as Serratia marcescens. The
      bacterium was found to produce several hydrolytic enzymes like chitinase,
      protease, lipase, cellulase and plant growth promoting metabolites like IAA and
      siderophore. Scanning electron microscopic studies on the interaction zone
      between pathogen and antagonistic bacterial isolate revealed severe deformities
      in the fungal mycelia. Spectral analyses (LC-ESI-MS, UV-VIS spectrophotometry and
      HPLC) and TLC indicated the presence of the antibiotics pyrrolnitrin and
      prodigiosin in the extracellular bacterial culture extracts. Biofilm formation by
      ETR17 on polystyrene surface was also observed. In vivo application of talc-based
      formulations prepared with the isolate ETR17 in tea plantlets under green house
      conditions revealed effective reduction of root-rot disease as well as plant
      growth promotion to a considerable extent. Viability studies with the ETR17 talc
      formulation showed the survivability of the isolate up to six months at room
      temperature. The sustenance of ETR17 (concentration of 8-9x108 cfu g-1) in the
      soil after the application of talc formulation was recorded by ELISA. Safety
      studies revealed that ETR17 did not produce hemolysin as observed in pathogenic
      Serratia strains. The biocontrol strain reported in this study can be used for
      field application in order to minimize the use of chemical fungicides for disease
      control in tea gardens.

PMID- 29466419
TI  - Involvement of an ABI-like protein and a Ca2+-ATPase in drought tolerance as
      revealed by transcript profiling of a sweetpotato somatic hybrid and its parents
      Ipomoea batatas (L.) Lam. and I. triloba L.
AB  - Previously, we obtained the sweetpotato somatic hybrid KT1 from a cross between
      sweetpotato (Ipomoea batatas (L.) Lam.) cv. Kokei No. 14 and its drought-tolerant
      wild relative I. triloba L. KT1 not only inherited the thick storage root
      characteristic of Kokei No. 14 but also the drought-tolerance trait of I. triloba
      L. The aim of this study was to explore the molecular mechanism of the drought
      tolerance of KT1. Four-week-old in vitro-grown plants of KT1, Kokei No. 14, and
      I. triloba L. were subjected to a simulated drought stress treatment (30%
      PEG6000) for 0, 6, 12 and 24 h. Total RNA was extracted from samples at each time
      point, and then used for transcriptome sequencing. The gene transcript profiles
      of KT1 and its parents were compared to identify differentially expressed genes,
      and drought-related modules were screened by a weighted gene co-expression
      network analysis. The functions of ABI-like protein and Ca2+-ATPase, two proteins
      screened from the cyan and light yellow modules, were analyzed in terms of their
      potential roles in drought tolerance in KT1 and its parents. These analyses of
      the drought responses of KT1 and its somatic donors at the transcriptional level
      provide new annotations for the molecular mechanism of drought tolerance in the
      somatic hybrid KT1 and its parents.

PMID- 29466420
TI  - Seeing through rose-colored glasses: How optimistic expectancies guide visual
      attention.
AB  - Optimism bias and positive attention bias have important highly similar
      implications for mental health but have only been examined in isolation.
      Investigating the causal relationships between these biases can improve the
      understanding of their underlying cognitive mechanisms, leading to new directions
      in neurocognitive research and revealing important information about normal
      functioning as well as the development, maintenance, and treatment of
      psychological diseases. In the current project, we hypothesized that optimistic
      expectancies can exert causal influences on attention deployment. To test this
      causal relation, we conducted two experiments in which we manipulated optimistic
      and pessimistic expectancies regarding future rewards and punishments. In a
      subsequent visual search task, we examined participants' attention to positive
      (i.e., rewarding) and negative (i.e., punishing) target stimuli, measuring their
      eye gaze behavior and reaction times. In both experiments, participants'
      attention was guided toward reward compared with punishment when optimistic
      expectancies were induced. Additionally, in Experiment 2, participants' attention
      was guided toward punishment compared with reward when pessimistic expectancies
      were induced. However, the effect of optimistic (rather than pessimistic)
      expectancies on attention deployment was stronger. A key characteristic of
      optimism bias is that people selectively update expectancies in an optimistic
      direction, not in a pessimistic direction, when receiving feedback. As revealed
      in our studies, selective attention to rewarding versus punishing evidence when
      people are optimistic might explain this updating asymmetry. Thus, the current
      data can help clarify why optimistic expectancies are difficult to overcome. Our
      findings elucidate the cognitive mechanisms underlying optimism and attention
      bias, which can yield a better understanding of their benefits for mental health.

PMID- 29466422
TI  - Does mental health staffing level affect antipsychotic prescribing? Analysis of
      Italian national statistics.
AB  - INTRODUCTION: In mental healthcare, one area of major concern identified by
      health information systems is variability in antipsychotic prescribing. While
      most studies have investigated patient- and prescriber-related factors as
      possible reasons for such variability, no studies have investigated facility
      level characteristics. The present study ascertained whether staffing level is
      associated with antipsychotic prescribing in community mental healthcare.
      METHODS: A cross-sectional analysis of data extracted from the Italian national
      mental health information system was carried out. For each Italian region, it
      collects data on the availability and use of mental health facilities. The rate
      of individuals exposed to antipsychotic drugs was tested for evidence of
      association with the rate of mental health staff availability by means of
      univariate and multivariate analyses. RESULTS: In Italy there were on average
      nearly 60 mental health professionals per 100,000 inhabitants, with wide regional
      variations (range 21 to 100). The average rate of individuals prescribed
      antipsychotic drugs was 2.33%, with wide regional variations (1.04% to 4.01%).
      Univariate analysis showed that the rate of individuals prescribed antipsychotic
      drugs was inversely associated with the rate of mental health professionals
      available in Italian regions (Kendall's tau -0.438, p = 0.006), with lower rates
      of antipsychotic prescriptions in regions with higher rates of mental health
      professionals. After adjustment for possible confounders, the total availability
      of mental health professionals was still inversely associated with the rate of
      individuals exposed to antipsychotic drugs. DISCUSSION: The evidence that
      staffing level was inversely associated with antipsychotic prescribing indicates
      that any actions aimed at decreasing variability in antipsychotic prescribing
      need to take into account aspects related to the organization of the mental
      health system.

PMID- 29466421
TI  - Protective effects and immunomodulation on piglets infected with rotavirus
      following resveratrol supplementation.
AB  - Rotavirus (RV), belonging to Reoviridae family, is the leading cause of acute
      severe viral diarrhea in children (under 5 years old) and infant animals
      worldwide. Although vaccines are commonly used to prevent infection, episodes of
      diarrhea caused by RV frequently occur. Thus, this study was conducted to
      determine whether resveratrol had protective effects against RV infection in
      piglets. Following pretreatment with resveratrol dry suspension through adding
      into the basal diet for 3 weeks, the piglets were orally challenged with RV. We
      found that resveratrol could alleviate diarrhea induced by RV infection.
      Resveratrol-treatment inhibited the TNF-alpha production, indicating that the
      anti-RV activity of resveratrol may be achieved by reducing the inflammatory
      response. The IFN-gamma level was elevated in 10mg/kg/d resveratrol-treated group
      and 30mg/kg/d resveratrol-treated group after RV infection. The ratios of
      CD4+/CD8+ in resveratrol-treated groups were the same as that in mock infected
      group, suggesting that resveratrol could maintain the immune function in RV
      infected piglets. It was found that resveratrol could alleviate diarrhea induced
      by RV infection. These results revealed that resveratrol dry suspension could be
      a new control measure for RV infection.

PMID- 29466423
TI  - Proteomic analysis of the human retina reveals region-specific susceptibilities
      to metabolic- and oxidative stress-related diseases.
AB  - Differences in regional protein expression within the human retina may explain
      molecular predisposition of specific regions to ophthalmic diseases like age
      related macular degeneration, cystoid macular edema, retinitis pigmentosa, and
      diabetic retinopathy. To quantify protein levels in the human retina and identify
      patterns of differentially-expressed proteins, we collected foveomacular, juxta
      macular, and peripheral retina punch biopsies from healthy donor eyes and
      analyzed protein content by liquid chromatography-tandem mass spectrometry (LC
      MS/MS). Protein expression was analyzed with 1-way ANOVA, gene ontology, pathway
      representation, and network analysis. We identified a mean of 1,974 proteins in
      the foveomacular retina, 1,999 in the juxta-macular retina, and 1,779 in the
      peripheral retina. Six hundred ninety-seven differentially-expressed proteins
      included those unique to and abundant in each anatomic region. Proteins with
      higher expression in each region include: heat-shock protein 90-alpha (HSP90AA1),
      and pyruvate kinase (PKM) in the foveomacular retina; vimentin (VIM) and fructose
      bisphosphate aldolase C (ALDOC); and guanine nucleotide-binding protein subunit
      beta-1 (GNB1) and guanine nucleotide-binding protein subunit alpha-1 (GNAT1) in
      the peripheral retina. Pathway analysis identified downstream mediators of the
      integrin signaling pathway to be highly represented in the foveomacular region (P
      = 6.48 e-06). Metabolic pathways were differentially expressed among all retinal
      regions. Gene ontology analysis showed that proteins related to antioxidant
      activity were higher in the juxta-macular and the peripheral retina, but present
      in lower amounts in the foveomacular retina. Our proteomic analysis suggests that
      certain retinal regions are susceptible to different forms of metabolic and
      oxidative stress. The findings give mechanistic insight into retina function,
      reveal important molecular processes, and prioritize new pathways for therapeutic
      targeting.

PMID- 29466424
TI  - Anterior segment and external ocular disorders associated with HIV infections in
      the era of HAART in Chiang Mai University Hospital, a prospective descriptive
      cross sectional study.
AB  - Human immunodeficiency virus (HIV) causes impairment to the human immune system
      which leads to immunocompromised conditions, including ocular complications.
      Several important HIV-associated disorders may involve the anterior segment,
      ocular surface, and adnexae organ such as dry eye, blepharitis which reduce
      quality of life of patients. In present, potent antiretroviral therapies HAART
      (highly active antiretroviral therapy) has improved the length and quality of
      life which may lead to an increased prevalence of anterior segment ocular
      disorders. Hence, this study has been undertaken to identify the prevalence and
      associated factors of anterior segment and external ocular disorder in HIV
      infected patients in the era of HAART. A prospective descriptive cross sectional
      study was carried out in HIV positive patients conducted at the Department of
      Ophthalmology, Chiang Mai University Hospital, from February 2014 to October
      2015. Detail history and ocular examination was carried out to examine for
      anterior segment and external ocular disorders. A total number of 363 patients
      were included for this prospective cross-sectional study. From the total of 363
      patients, 123 patients had an anterior segment and external ocular disorder which
      account as the prevalence of 33.9%. The most common anterior segment
      manifestations was dry eye seen in 36 patients (9.9%), followed by posterior
      blepharitis (Meibomian gland dysfunction) seen in 23 patients (6.3%) and anterior
      blepharitis seen in 12 patients (3.3%). Other ocular complications included
      microvasculopathy, immune recovery uveitis, conjunctivitis, papilloma, anterior
      uveitis, corneal ulcer, nevus, trichiasis, molluscum contangiosum, Kaposi
      sarcoma, interstitial keratitis, conjunctival lymphangiectasia, dacryocystitis,
      vernal keratoconjunctivitis and eyelid penicilosis. In this study, the prevalance
      of anterior segment disorders was higher than in the preHAART era. Dry eye,
      blepharitis and uveitis were the top three most common anterior segment disorders
      in the HAART era. The statistical analysis showed no association between age,
      sex, CD4 count, duration of infection or receiving HAART and anterior segment
      disorders. Anterior segment abnormalities reduce the quality of life of patients,
      so ophthalmologists have to be aware and complete ocular examination should be
      performed in all HIV infected patients.

PMID- 29466425
TI  - Institutional transparency improves public perception of lab animal technicians
      and support for animal research.
AB  - The use of animals in research is controversial and often takes place under a
      veil of secrecy. Lab animal technicians responsible for the care of animals at
      research institutions are sometimes described as performing 'dirty work' (i.e.
      professions that are viewed as morally tainted), and may be stigmatized by
      negative perceptions of their job. This study assessed if transparency affects
      public perceptions of lab animal technicians and support for animal research.
      Participants (n = 550) were randomly assigned to one of six scenarios (using a
      3x2 design) that described identical research varying only the transparency of
      the facility (low, high) and the species used (mice, dogs, cows). Participants
      provided Likert-type and open-ended responses to questions about the personal
      characteristics (warmth, competence) of a hypothetical lab technician 'Cathy' and
      their support for the described research. Quantitative analysis showed
      participants in the low-transparency condition perceived Cathy to be less warm
      and were less supportive of the research regardless of animal species.
      Qualitative responses varied greatly, with some participants expressing support
      for both Cathy and the research. These results suggest that increasing
      transparency in lab animal institutions could result in a more positive
      perception of lab animal researchers and the work that they do.

PMID- 29466426
TI  - Archaeological and anthropological studies on the Harappan cemetery of
      Rakhigarhi, India.
AB  - An insufficient number of archaeological surveys has been carried out to date on
      Harappan Civilization cemeteries. One case in point is the necropolis at
      Rakhigarhi site (Haryana, India), one of the largest cities of the Harappan
      Civilization, where most burials within the cemetery remained uninvestigated.
      Over the course of the past three seasons (2013 to 2016), we therefore conducted
      excavations in an attempt to remedy this data shortfall. In brief, we found
      different kinds of graves co-existing within the Rakhigarhi cemetery in varying
      proportions. Primary interment was most common, followed by the use of secondary,
      symbolic, and unused (empty) graves. Within the first category, the atypical
      burials appear to have been elaborately prepared. Prone-positioned internments
      also attracted our attention. Since those individuals are not likely to have been
      social deviants, it is necessary to reconsider our pre-conceptions about such
      prone-position burials in archaeology, at least in the context of the Harappan
      Civilization. The data presented in this report, albeit insufficient to provide a
      complete understanding of Harappan Civilization cemeteries, nevertheless does
      present new and significant information on the mortuary practices and
      anthropological features at that time. Indeed, the range of different kinds of
      burials at the Rakhigarhi cemetery do appear indicative of the differences in
      mortuary rituals seen within Harappan societies, therefore providing a vivid
      glimpse of how these people respected their dead.

PMID- 29466427
TI  - Endothelial mineralocorticoid receptor ablation does not alter blood pressure,
      kidney function or renal vessel contractility.
AB  - Aldosterone blockade confers substantial cardiovascular and renal protection. The
      effects of aldosterone on mineralocorticoid receptors (MR) expressed in
      endothelial cells (EC) within the renal vasculature have not been delineated. We
      hypothesized that lack of MR in EC may be protective in renal vasculature and
      examined this by ablating the Nr3c2 gene in endothelial cells (EC-MR) in mice.
      Blood pressure, heart rate and PAH clearance were measured using indwelling
      catheters in conscious mice. The role of the MR in EC on contraction and
      relaxation was investigated in the renal artery and in perfused afferent
      arterioles. Urinary sodium excretion was determined by use of metabolic cages. EC
      MR transgenics had markedly decreased MR expression in isolated aortic
      endothelial cells as compared to littermates (WT). Blood pressure and effective
      renal plasma flow at baseline and following AngII infusion was similar between
      groups. No differences in contraction and relaxation were observed between WT and
      EC-MR KO in isolated renal arteries during baseline or following 2 or 4 weeks of
      AngII infusion. The constriction or dilatations of afferent arterioles between
      genotypes were not different. No changes were found between the groups with
      respect to urinary excretion of sodium after 4 weeks of AngII infusion, or in
      urinary albumin excretion and kidney morphology. In conclusion, deletion of the
      EC-MR does not confer protection towards the development of hypertension,
      endothelial dysfunction of renal arteries or renal function following prolonged
      AngII-infusion.

PMID- 29466428
TI  - Hemagglutinin-specific neutralization of subacute sclerosing panencephalitis
      viruses.
AB  - Subacute sclerosing panencephalitis (SSPE) is a progressive, lethal complication
      of measles caused by particular mutants of measles virus (MeV) that persist in
      the brain despite high levels of neutralizing antibodies. We addressed the
      hypothesis that antigenic drift is involved in the pathogenetic mechanism of SSPE
      by analyzing antigenic alterations in the MeV envelope hemagglutinin protein (MeV
      H) found in patients with SSPE in relation to major circulating MeV genotypes. To
      this aim, we obtained cDNA for the MeV-H gene from tissue taken at brain autopsy
      from 3 deceased persons with SSPE who had short (3-4 months, SMa79), average (3.5
      years, SMa84), and long (18 years, SMa94) disease courses. Recombinant MeVs with
      a substituted MeV-H gene were generated by a reverse genetic system. Virus
      neutralization assays with a panel of anti-MeV-H murine monoclonal antibodies
      (mAbs) or vaccine-immunized mouse anti-MeV-H polyclonal sera were performed to
      determine the antigenic relatedness. Functional and receptor-binding analysis of
      the SSPE MeV-H showed activity in a SLAM/nectin-4-dependent manner. Similar to
      our panel of wild-type viruses, our SSPE viruses showed an altered antigenic
      profile. Genotypes A, G3, and F (SSPE case SMa79) were the exception, with an
      intact antigenic structure. Genotypes D7 and F (SSPE SMa79) showed enhanced
      neutralization by mAbs targeting antigenic site IIa. Genotypes H1 and the
      recently reported D4.2 were the most antigenically altered genotypes. Epitope
      mapping of neutralizing mAbs BH015 and BH130 reveal a new antigenic site on MeV
      H, which we designated Phi for its intermediate position between previously
      defined antigenic sites Ia and Ib. We conclude that SSPE-causing viruses show
      similar antigenic properties to currently circulating MeV genotypes. The absence
      of a direct correlation between antigenic changes and predisposition of a certain
      genotype to cause SSPE does not lend support to the proposed antigenic drift as a
      pathogenetic mechanism in SSPE.

PMID- 29466429
TI  - Population nutrikinetics of green tea extract.
AB  - : Green tea polyphenols may contribute to the prevention of cancer and other
      diseases. To learn more about the pharmacokinetics and interindividual variation
      of green tea polyphenols after oral intake in humans we performed a population
      nutrikinetic study of standardized green tea extract. 84 healthy participants
      took green tea extract capsules standardized to 150 mg epigallocatechin-gallate
      (EGCG) twice a day for 5 days. On day 5 catechin plasma concentrations were
      analyzed using non-compartmental and population pharmacokinetic methods. A strong
      between-subject variability in catechin pharmacokinetics was found with maximum
      plasma concentrations varying more than 6-fold. The AUCs of EGCG, EGC and ECG
      were 877.9 (360.8-1576.5), 35.1 (8.0-87.4), and 183.6 (55.5-364.6) h*MUg/L
      respectively, and the elimination half lives were 2.6 (1.8-3.8), 3.9 (0.9-10.7)
      and 1.8 (0.8-2.9) h, respectively. Genetic polymorphisms in genes of the drug
      transporters MRP2 and OATP1B1 could at least partly explain the high variability
      in pharmacokinetic parameters. The observed variability in catechin plasma levels
      might contribute to interindividual variation in benefical and adverse effects of
      green tea polyphenols. Our data could help to gain a better understanding of the
      causes of variability of green tea effects and to improve the design of studies
      on the effects of green tea polyphenols in different health conditions. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01360320.

PMID- 29466430
TI  - Cholinergic signaling mediates the effects of xenin-25 on secretion of pancreatic
      polypeptide but not insulin or glucagon in humans with impaired glucose
      tolerance.
AB  - We previously demonstrated that infusion of an intestinal peptide called xenin-25
      (Xen) amplifies the effects of glucose-dependent insulinotropic polypeptide (GIP)
      on insulin secretion rates (ISRs) and plasma glucagon levels in humans. However,
      these effects of Xen, but not GIP, were blunted in humans with type 2 diabetes.
      Thus, Xen rather than GIP signaling to islets fails early during development of
      type 2 diabetes. The current crossover study determines if cholinergic signaling
      relays the effects of Xen on insulin and glucagon release in humans as in mice.
      Fasted subjects with impaired glucose tolerance were studied. On eight separate
      occasions, each person underwent a single graded glucose infusion- two each with
      infusion of albumin, Xen, GIP, and GIP plus Xen. Each infusate was administered
      +/- atropine. Heart rate and plasma glucose, insulin, C-peptide, glucagon, and
      pancreatic polypeptide (PP) levels were measured. ISRs were calculated from C
      peptide levels. All peptides profoundly increased PP responses. From 0 to 40 min,
      peptide(s) infusions had little effect on plasma glucose concentrations. However,
      GIP, but not Xen, rapidly and transiently increased ISRs and glucagon levels.
      Both responses were further amplified when Xen was co-administered with GIP. From
      40 to 240 min, glucose levels and ISRs continually increased while glucagon
      concentrations declined, regardless of infusate. Atropine increased resting heart
      rate and blocked all PP responses but did not affect ISRs or plasma glucagon
      levels during any of the peptide infusions. Thus, cholinergic signaling mediates
      the effects of Xen on insulin and glucagon release in mice but not humans.

PMID- 29466432
TI  - The role of pre-existing comorbidity on the rate of recovery following injury: A
      longitudinal cohort study.
AB  - Understanding the role of comorbidity in recovery following injury is an
      important challenge given the increasing prevalence of multimorbidity (2 or more
      comorbidities) in many countries. The Prospective Outcomes of Injury Study
      recruited 2856 injured 18-64 year olds that had registered for entitlements with
      New Zealand's universal no-fault injury insurer. Recovery, or lack of, in this
      longitudinal cohort was measured using the World Health Organization Disability
      Assessment Schedule at 3, 12 and 24 months post-injury. Twenty-one pre-existing
      chronic conditions were used to identify comorbidity. To investigate whether
      rates of recovery differed by pre-injury comorbidity, the interaction between
      time and comorbidity was modelled using Generalised Estimating Equations. Of
      1,862 participants with complete data, the distribution reporting none, one
      comorbidity, or multimorbidity pre-injury was 51%, 27%, and 21% respectively.
      Longitudinal analysis estimated no difference (log odds per year 0.05, 95%
      Confidence Interval -0.17 to 0.27) between the rate of change of disability for
      those with one pre-injury comorbidity compared to those with none. Those with pre
      injury multimorbidity had significantly slower reduction in disability over time
      than those with no pre-injury comorbidity (log odds per year 0.27, 95% Confidence
      Interval 0.05 to 0.48). In a working age cohort, the rate of recovery in the 24
      months following injury was similar for those with none or one pre-existing
      comorbidity and significantly slower for those with multimorbidity. It is
      important that further research explores mechanisms driving this, and that
      researchers and health providers identify and implement better supports for
      injured people with multimorbidity.

PMID- 29466433
TI  - Novel optimization technique of isolated microgrid with hydrogen energy storage.
AB  - This paper presents a novel optimization technique for energy management studies
      of an isolated microgrid. The system is supplied by various Distributed Energy
      Resources (DERs), Diesel Generator (DG), a Wind Turbine Generator (WTG),
      Photovoltaic (PV) arrays and supported by fuel cell/electrolyzer Hydrogen storage
      system for short term storage. Multi-objective optimization is used through non
      dominated sorting genetic algorithm to suit the load requirements under the given
      constraints. A novel multi-objective flower pollination algorithm is utilized to
      check the results. The Pros and cons of the two optimization techniques are
      compared and evaluated. An isolated microgrid is modelled using MATLAB software
      package, dispatch of active/reactive power, optimal load flow analysis with slack
      bus selection are carried out to be able to minimize fuel cost and line losses
      under realistic constraints. The performance of the system is studied and
      analyzed during both summer and winter conditions and three case studies are
      presented for each condition. The modified IEEE 15 bus system is used to validate
      the proposed algorithm.

PMID- 29466431
TI  - Cryptic genetic diversity in the mottled rabbitfish Siganus fuscescens with
      mitochondrial introgression at a contact zone in the South China Sea.
AB  - The taxonomy of the mottled rabbitfish Siganus fuscescens species complex has
      long been challenging. In this study, we analyzed microsatellite genotypes,
      mitochondrial lineages, and morphometric data from 373 S. fuscescens individuals
      sampled from the northern Philippines and Hong Kong (South China Sea, Philippine
      Sea and Sulu Sea basins), to examine putative species boundaries in samples
      comprising three co-occurring mitochondrial lineages previously reported to
      characterize S. fuscescens (Clade A and Clade B) or S. canaliculatus (Clade C).
      We report the existence of two cryptic species within S. fuscescens in the
      northeast region of the South China Sea and northern Philippine Sea, supported by
      genetic and morphological differences. Individual-based assignment methods
      recovered concordant groupings of individuals into two nuclear genotype clusters
      (Cluster 1, Cluster 2) with (1) limited gene flow, if any, between them (FST =
      0.241; P < 0.001); (2) low frequency of later-generation hybrids; (3) significant
      association with mitochondrial Clade A and Clade B, respectively; and (4) subtle
      yet significant body shape differences as inferred from geometric morphometric
      analysis. The divergence between mitochondrial Clade C and the two other clades
      was not matched by genetic differences at microsatellite marker loci. The
      occurrence of discordant mitonuclear combinations (20.5% of the total number of
      individuals) is thought to result from mitochondrial introgression, consistent
      with a scenario of demographic, and presumably spatial, post-Pleistocene
      expansion of populations from northern regions into a secondary contact zone in
      the South China Sea. Mitonuclear discordance due to introgression obscures
      phylogenetic relationships for recently-diverged lineages, and cautions against
      the use of mitochondrial markers alone for species identification within the
      mottled rabbitfish species complex in the South China Sea region.

PMID- 29466434
TI  - Nutritional intra-amniotic therapy increases survival in a rabbit model of fetal
      growth restriction.
AB  - OBJECTIVE: To evaluate the perinatal effects of a prenatal therapy based on intra
      amniotic nutritional supplementation in a rabbit model of intrauterine growth
      restriction (IUGR). METHODS: IUGR was surgically induced in pregnant rabbits at
      gestational day 25 by ligating 40-50% of uteroplacental vessels of each
      gestational sac. At the same time, modified-parenteral nutrition solution
      (containing glucose, amino acids and electrolytes) was injected into the amniotic
      sac of nearly half of the IUGR fetuses (IUGR-T group n = 106), whereas sham
      injections were performed in the rest of fetuses (IUGR group n = 118). A control
      group without IUGR induction but sham injection was also included (n = 115). Five
      days after the ligation procedure, a cesarean section was performed to evaluate
      fetal cardiac function, survival and birth weight. RESULTS: Survival was
      significantly improved in the IUGR fetuses that were treated with intra-amniotic
      nutritional supplementation as compared to non-treated IUGR animals (survival
      rate: controls 71% vs. IUGR 44% p = 0.003 and IUGR-T 63% vs. IUGR 44% p = 0.02),
      whereas, birth weight (controls mean 43g +/- SD 9 vs. IUGR 36g +/- SD 9 vs. IUGR
      T 35g +/- SD 8, p = 0.001) and fetal cardiac function were similar among the IUGR
      groups. CONCLUSION: Intra-amniotic injection of a modified-parenteral nutrient
      solution appears to be a promising therapy for reducing mortality among IUGR.
      These results provide an opportunity to develop new intra-amniotic nutritional
      strategies to reach the fetus by bypassing the placental insufficiency.

PMID- 29466435
TI  - Separate analysis of human papillomavirus E6 and E7 messenger RNAs to predict
      cervical neoplasia progression.
AB  - A few studies previously suggested that human papillomavirus (HPV) E6 messenger
      RNA (mRNA) may exist uniformly in all grades of cervical intraepithelial
      neoplasia (CIN), whereas the detection rate of E7 mRNA may increase with disease
      progression from low-grade CIN to invasive carcinoma. The aim of this study was
      to clarify the different roles of E6 and E7 mRNAs in cervical carcinogenesis. The
      presence of each E6 and E7 mRNA was analyzed in 171 patients with pathologically
      diagnosed CIN or cervical carcinoma. We utilized a RT-PCR assay based on
      consensus primers which could detect E6 mRNA (full-length E6/E7 transcript) and
      E7 mRNAs (spliced E6*/E7 transcripts) separately for various HPV types. E7 mRNAs
      were detected in 6% of CIN1, 12% of CIN2, 24% of CIN3, and 54% of cervical
      carcinoma. The presence of E7 mRNAs was significantly associated with progression
      from low-grade CIN to invasive carcinoma in contrast with E6 mRNA or high-risk
      HPV (HR-HPV) DNA (p = 0.00011, 0.80 and 0.54). The presence of both E6 and E7
      mRNAs was significantly associated with HPV16/18 DNA but not with HR-HPV DNA (p =
      0.0079 and 0.21), while the presence of E6 mRNA was significantly associated with
      HR-HPV DNA but not with HPV16/18 DNA (p = 0.036 and 0.089). The presence of both
      E6 and E7 mRNAs showed high specificity and low sensitivity (100% and 19%) for
      detecting CIN2+ by contrast with the positivity for HR-HPV DNA showing low
      specificity and high sensitivity (19% and 89%). The positive predictive value for
      detecting CIN2+ was even higher by the presence of both E6 and E7 mRNAs than by
      the positivity for HR-HPV DNA (100% vs. 91%). In 31 patients followed up for CIN1
      2, the presence of both E6 and E7 mRNAs showed significant association with the
      occurrence of upgraded abnormal cytology in contrast with E6 mRNA, HR-HPV DNA, or
      HPV16/18 DNA (p = 0.034, 0.73, 0.53, and 0.72). Our findings support previous
      studies according to which E7 mRNA is more closely involved in cervical
      carcinogenesis than E6 mRNA. Moreover, the separate analysis of E6 and E7 mRNAs
      may be more useful than HR-HPV DNA test for detecting CIN2+ precisely and
      predicting disease progression. Further accumulation of evidence is warranted to
      validate our findings.

PMID- 29466437
TI  - Correction: Metabolomics based predictive biomarker model of ARDS: A systemic
      measure of clinical hypoxemia.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187545.].

PMID- 29466436
TI  - Loss of HCN2 leads to delayed gastrointestinal motility and reduced energy intake
      in mice.
AB  - Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are important
      regulators of excitability in neural, cardiac, and other pacemaking cells, which
      are often altered in disease. In mice, loss of HCN2 leads to cardiac
      dysrhythmias, persistent spike-wave discharges similar to those seen in absence
      epilepsy, ataxia, tremor, reduced neuropathic and inflammatory pain,
      antidepressant-like behavior, infertility, and severely restricted growth. While
      many of these phenotypes have tissue-specific mechanisms, the cause of restricted
      growth in HCN2 knockout animals remains unknown. Here, we characterize a novel,
      3kb insertion mutation of Hcn2 in the Tremor and Reduced Lifespan 2 (TRLS/2J)
      mouse that leads to complete loss of HCN2 protein, and we show that this mutation
      causes many phenotypes similar to other mice lacking HCN2 expression. We then
      demonstrate that while TRLS/2J mice have low blood glucose levels and impaired
      growth, dysfunction in hormonal secretion from the pancreas, pituitary, and
      thyroid are unlikely to lead to this phenotype. Instead, we find that homozygous
      TRLS/2J mice have abnormal gastrointestinal function that is characterized by
      less food consumption and delayed gastrointestinal transit as compared to
      wildtype mice. In summary, a novel mutation in HCN2 likely leads to impaired GI
      motility, causing the severe growth restriction seen in mice with mutations that
      eliminate HCN2 expression.

PMID- 29466438
TI  - Correction: Characteristics of the memory sources of dreams: A new version of the
      content-matching paradigm to take mundane and remote memories into account.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185262.].

PMID- 29466440
TI  - Predictors of activities of daily living outcomes after upper limb robot-assisted
      therapy in subacute stroke patients.
AB  - BACKGROUND: Upper limb recovery is one of the main goals of post-stroke
      rehabilitation due to its importance for autonomy in Activities of Daily Living
      (ADL). Although the efficacy of upper limb Robot-assisted Therapy (RT) is well
      established in literature, the impact of the initial status of the patient on the
      effects of RT is still understudied. This paper aims to identify whether
      demographic, clinical and motor characteristics of stroke patients may influence
      the ability to independently perform ADL after RT. METHODS: A retrospective study
      was conducted on sixty stroke patients who conducted planar upper limb goal
      directed tasks with the InMotion 2.0 robot. The RT was administered 5 days/week
      for 4 weeks and each session lasted 45 minutes. The primary outcome measure was
      the Modified Barthel Index (BI), dichotomized into favourable (BI >=75) and
      unfavourable (BI<75) outcomes. The potential predictors were the demographic and
      clinical records, and the following clinical assessment scores: Modified Ashworth
      Scale-Shoulder (MAS-S); Modified Ashworth Scale-Elbow (MAS-E); Fugl-Meyer
      Assessment Upper Extremity (FMA-UE); upper limb section of the Motricity Index
      (MIul); total passive Range Of Motion (pROM); and Box and Block Test (BBT).
      RESULTS: Statistical analysis showed that the BBT, FMA-UE and MIul scores were
      significant predictors of a favourable outcome in ADL. The cut-off scores of the
      independent variables were calculated (FMA-UE = 32; MIul = 48; BBT = 3) with
      respect to the dichotomic BI outcome. Their robustness was assessed with the
      Fragility Index (FMA-UE = 2; MIul = 3; BBT = 7), showing that BBT is the most
      robust predictor of favourable BI outcome. Moreover, subjects with all predictors
      higher than the cut-off scores had higher probability to increase their
      independence in ADL at the end of the therapy. Demographic records, spasticity
      and pROM were not identified as predictors. CONCLUSION: Stroke patients with
      greater manual dexterity and less impairment appear to have a higher probability
      of achieving clinically significant ADL outcomes after upper limb RT. The
      obtained results can help to optimise the management of RT treatment planning.
      Further studies on a larger number of patients with a long-term follow up are
      recommended in order to evaluate other potential predictors and to validate the
      results.

PMID- 29466441
TI  - Correction: Impact of extensive antibiotic treatment on faecal carriage of
      antibiotic-resistant enterobacteria in children in a low resistance prevalence
      setting.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187618.].

PMID- 29466439
TI  - Liver macrophage-associated inflammation correlates with SIV burden and is
      substantially reduced following cART.
AB  - Liver disease is a leading contributor to morbidity and mortality during HIV
      infection, despite the use of combination antiretroviral therapy (cART). The
      precise mechanisms of liver disease during HIV infection are poorly understood
      partially due to the difficulty in obtaining human liver samples as well as the
      presence of confounding factors (e.g. hepatitis co-infection, alcohol use).
      Utilizing the simian immunodeficiency virus (SIV) macaque model, a controlled
      study was conducted to evaluate the factors associated with liver inflammation
      and the impact of cART. We observed an increase in hepatic macrophages during
      untreated SIV infection that was associated with a number of inflammatory and
      fibrosis mediators (TNFalpha, CCL3, TGFbeta). Moreover, an upregulation in the
      macrophage chemoattractant factor CCL2 was detected in the livers of SIV-infected
      macaques that coincided with an increase in the number of activated CD16+
      monocyte/macrophages and T cells expressing the cognate receptor CCR2. Expression
      of Mac387 on monocyte/macrophages further indicated that these cells recently
      migrated to the liver. The hepatic macrophage and T cell levels strongly
      correlated with liver SIV DNA levels, and were not associated with the levels of
      16S bacterial DNA. Utilizing in situ hybridization, SIV-infected cells were found
      primarily within portal triads, and were identified as T cells. Microarray
      analysis identified a strong antiviral transcriptomic signature in the liver
      during SIV infection. In contrast, macaques treated with cART exhibited lower
      levels of liver macrophages and had a substantial, but not complete, reduction in
      their inflammatory profile. In addition, residual SIV DNA and bacteria 16S DNA
      were detected in the livers during cART, implicating the liver as a site on-going
      immune activation during antiretroviral therapy. These findings provide
      mechanistic insights regarding how SIV infection promotes liver inflammation
      through macrophage recruitment, with implications for in HIV-infected
      individuals.

PMID- 29466442
TI  - Soluble adenylyl cyclase: A novel player in cardiac hypertrophy induced by
      isoprenaline or pressure overload.
AB  - AIMS: In contrast to the membrane bound adenylyl cyclases, the soluble adenylyl
      cyclase (sAC) is activated by bicarbonate and divalent ions including calcium.
      sAC is located in the cytosol, nuclei and mitochondria of several tissues
      including cardiac muscle. However, its role in cardiac pathology is poorly
      understood. Here we investigate whether sAC is involved in hypertrophic growth
      using two different model systems. METHODS AND RESULTS: In isolated adult rat
      cardiomyocytes hypertrophy was induced by 24 h beta1-adrenoceptor stimulation
      using isoprenaline (ISO) and a beta2-adrenoceptor antagonist (ICI118,551). To
      monitor hypertrophy cell size along with RNA/DNA- and protein/DNA ratios as well
      as the expression level of alpha-skeletal actin were analyzed. sAC activity was
      suppressed either by treatment with its specific inhibitor KH7 or by knockdown.
      Both pharmacological inhibition and knockdown blunted hypertrophic growth and
      reduced expression levels of alpha-skeletal actin in ISO/ICI treated rat
      cardiomyocytes. To analyze the underlying cellular mechanism expression levels of
      phosphorylated CREB, B-Raf and Erk1/2 were examined by western blot. The results
      suggest the involvement of B-Raf, but not of Erk or CREB in the pro-hypertrophic
      action of sAC. In wild type and sAC knockout mice pressure overload was induced
      by transverse aortic constriction. Hemodynamics, heart weight and the expression
      level of the atrial natriuretic peptide were analyzed. In accordance, transverse
      aortic constriction failed to induce hypertrophy in sAC knockout mice.
      Mechanistic analysis revealed a potential role of Erk1/2 in TAC-induced
      hypertrophy. CONCLUSION: Soluble adenylyl cyclase might be a new pivotal player
      in the cardiac hypertrophic response either to long-term beta1-adrenoceptor
      stimulation or to pressure overload.

PMID- 29466444
TI  - Analysis of aluminum toxicity in Hordeum vulgare roots with an emphasis on DNA
      integrity and cell cycle.
AB  - Barley is one of the cereals that are most sensitive to aluminum (Al). Al in acid
      soils limits barley growth and development and, as a result, its productivity.
      The inhibition of root growth is a widely accepted indicator of Al stress. Al
      toxicity is affected by many factors including the culture medium, pH, Al
      concentration and the duration of the treatment. However, Al can act differently
      in different species and still Al toxicity in barley deserves study. Since the
      mechanism of Al toxicity is discussed we cytogenetically describe the effects of
      different doses of bioavailable Al on the barley nuclear genome-mitotic activity,
      cell cycle profile and DNA integrity. At the same time, we tested an established
      deep-water culture (DWC) hydroponics system and analyzed the effects of Al on the
      root system parameters using WinRHIZO software. We demonstrated the cytotoxic and
      genotoxic effect of Al in barley root cells. We showed that Al treatment
      significantly reduced the mitotic activity of the root tip cells and it also
      induced micronuclei and damaged nuclei. The DNA-damaging effect of Al was
      observed using the TUNEL test. We define the inhibitory influence of Al on DNA
      replication in barley. Analysis with the labelling and detection of 5-ethynyl-2'
      deoxyuridin (EdU) showed that the treatment with Al significantly decreased the
      frequency of S phase cells. We also demonstrated that Al exposure led to changes
      in the cell cycle profile of barley root tips. The delay of cell divisions
      observed as increased frequency of cells in G2/M phase after Al treatment was
      reported using flow cytometry.

PMID- 29466443
TI  - Burnout and self-reported suboptimal patient care amongst health care workers
      providing HIV care in Malawi.
AB  - BACKGROUND: The well-documented shortages of health care workers (HCWs) in sub
      Saharan Africa are further intensified by the increased human resource needs of
      expanding HIV treatment programs. Burnout is a syndrome of emotional exhaustion
      (EE), depersonalization (DP), and a sense of low personal accomplishment (PA).
      HCWs' burnout can negatively impact the delivery of health services. Our main
      objective was to examine the prevalence of burnout amongst HCWs in Malawi and
      explore its relationship to self-reported suboptimal patient care. METHODS: A
      cross-sectional study among HCWs providing HIV care in 89 facilities, across
      eight districts in Malawi was conducted. Burnout was measured using the Maslach
      Burnout Inventory defined as scores in the mid-high range on the EE or DP
      subscales. Nine questions adapted for this study assessed self-reported
      suboptimal patient care. Surveys were administered anonymously and included socio
      demographic and work-related questions. Validated questionnaires assessed
      depression and at-risk alcohol use. Chi-square test or two-sample t-test was used
      to explore associations between variables and self-reported suboptimal patient
      care. Bivariate analyses identified candidate variables (p < 0.2). Final
      regression models included variables with significant main effects. RESULTS: Of
      520 HCWs, 62% met criteria for burnout. In the three dimensions of burnout, 55%
      reported moderate-high EE, 31% moderate-high DP, and 46% low-moderate PA. The
      majority (89%) reported engaging in suboptimal patient care/attitudes including
      making mistakes in treatment not due to lack of knowledge/experience (52%),
      shouting at patients (45%), and not performing diagnostic tests due to a desire
      to finish quickly (35%). In multivariate analysis, only burnout remained
      associated with self-reported suboptimal patient care (OR 3.22, [CI 2.11 to
      4.90]; p<0.0001). CONCLUSION: Burnout was common among HCWs providing HIV care
      and was associated with self-reported suboptimal patient care
      practices/attitudes. Research is needed to understand factors that contribute to
      and protect against burnout and that inform the development of strategies to
      reduce burnout.

PMID- 29466445
TI  - The BPA-substitute bisphenol S alters the transcription of genes related to
      endocrine, stress response and biotransformation pathways in the aquatic midge
      Chironomus riparius (Diptera, Chironomidae).
AB  - Bisphenol S (BPS) is an industrial alternative to the endocrine disruptor
      bisphenol A (BPA), and can be found in many products labeled "BPA-free". Its use
      has grown in recent years, and presently it is considered a ubiquitous emerging
      pollutant. To date there is a lack of information on the effects of BPS on
      invertebrates, although they represent more than 95% of known species in the
      animal kingdom and are crucial for the structure and proper function of
      ecosystems. In this study, real-time RT-PCR was used to determine the early
      detrimental effects of BPS on the transcriptional rate of genes in the model
      species Chironomus riparius, specifically those related to the ecdysone pathway
      (EcR, ERR, E74, Vtg, cyp18a1) crucial for insect development and metamorphosis,
      stress and biotransformation mechanisms (hsp70, hsp40, cyp4g, GPx, GSTd3) that
      regulate adaptive responses and determine survival, and ribosome biogenesis
      (its2, rpL4, rpL13) which is essential for protein synthesis and homeostasis.
      While 24-hour exposure to 0.5, 5, 50, and 500 MUg/L BPS had no effect on larval
      survival, almost all the studied genes were upregulated following a non-monotonic
      dose-response curve. Genes with the greatest increases in transcriptional
      activity (fold change relative to control) were EcR (3.8), ERR (2), E74 (2.4),
      cyp18a1 (2.5), hsp70 (1.7), hsp40 (2.5), cyp4g (6.4), GPx (1.8), and GST (2.1),
      while others including Vtg, GAPDH, and selected ribosomal genes remained stable.
      We also measured the transcriptional activity of these genes 24 hours after BPS
      withdrawal and a general downregulation compared to controls was observed, though
      not significant in most cases. Our findings showed that BPS exposure altered the
      transcriptional profile of these genes, which may have consequences for the
      hormone system and several metabolic pathways. Although further research is
      needed to elucidate its mode of action, these results raise new concerns about
      the safety of BPA alternatives.

PMID- 29466447
TI  - Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron
      overload assessment.
AB  - BACKGROUND: Iron overload-related heart failure is the principal cause of death
      in transfusion dependent patients, including those with Thalassemia Major.
      Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1
      mapping can also measure iron; preliminary data suggests it may have higher
      sensitivity for iron, particularly for early overload (the conventional cut-point
      for no iron by T2* is 20ms, but this is believed insensitive). We compared T1
      mapping to T2* in cardiac iron overload. METHODS: In a prospectively large single
      centre study of 138 Thalassemia Major patients and 32 healthy controls, we
      compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear
      regression analysis was used to assess the association of T2* and T1. A "moving
      window" approach was taken to understand the strength of the association at
      different levels of iron overload. RESULTS: The relationship between T2* (here
      dark blood) and T1 is described by a log-log linear regression, which can be
      split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms,
      r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1;
      among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2*
      range 20-30ms having a low T1. CONCLUSIONS: In established cardiac iron overload,
      T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears
      to detect iron. These data support previous suggestions that T1 detects missed
      iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary
      to T2*. The clinical significance of a low T1 with normal T2* should be further
      investigated.

PMID- 29466446
TI  - The cannabinoid-1 receptor is abundantly expressed in striatal striosomes and
      striosome-dendron bouquets of the substantia nigra.
AB  - Presynaptic cannabinoid-1 receptors (CB1-R) bind endogenous and exogenous
      cannabinoids to modulate neurotransmitter release. CB1-Rs are expressed
      throughout the basal ganglia, including striatum and substantia nigra, where they
      play a role in learning and control of motivated actions. However, the pattern of
      CB1-R expression across different striatal compartments, microcircuits and
      efferent targets, and the contribution of different CB1-R-expressing neurons to
      this pattern, are unclear. We use a combination of conventional techniques and
      novel genetic models to evaluate CB1-R expression in striosome (patch) and matrix
      compartments of the striatum, and in nigral targets of striatal medium spiny
      projection neurons (MSNs). CB1-R protein and mRNA follow a descending
      dorsolateral-to-ventromedial intensity gradient in the caudal striatum, with
      elevated expression in striosomes relative to the surrounding matrix. The lateral
      predominance of striosome CB1-Rs contrasts with that of the classical striosomal
      marker, the mu opioid receptor (MOR), which is expressed most prominently in
      rostromedial striosomes. The dorsolateral-to-ventromedial CB1-R gradient is
      similar to Drd2 dopamine receptor immunoreactivity and opposite to Substance P.
      This topology of CB1-R expression is maintained downstream in the globus pallidus
      and substantia nigra. Dense CB1-R-expressing striatonigral fibers extend dorsally
      within the substantia nigra pars reticulata, and colocalize with bundles of
      ventrally extending, striosome-targeted, dendrites of dopamine-containing neurons
      in the substantia nigra pars compacta (striosome-dendron bouquets). Within
      striatum, CB1-Rs colocalize with fluorescently labeled MSN collaterals within the
      striosomes. Cre recombinase-mediated deletion of CB1-Rs from cortical projection
      neurons or MSNs, and MSN-selective reintroduction of CB1-Rs in knockout mice,
      demonstrate that the principal source of CB1-Rs in dorsolateral striosomes is
      local MSN collaterals. These data suggest a role for CB1-Rs in caudal
      dorsolateral striosome collaterals and striosome-dendron bouquet projections to
      lateral substantia nigra, where they are anatomically poised to mediate
      presynaptic disinhibition of both striosomal MSNs and midbrain dopamine neurons
      in response to endocannabinoids and cannabinomimetics.

PMID- 29466448
TI  - A dystrophic Duchenne mouse model for testing human antisense oligonucleotides.
AB  - Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease generally
      caused by reading frame disrupting mutations in the DMD gene resulting in loss of
      functional dystrophin protein. The reading frame can be restored by antisense
      oligonucleotide (AON)-mediated exon skipping, allowing production of internally
      deleted, but partially functional dystrophin proteins as found in the less severe
      Becker muscular dystrophy. Due to genetic variation between species, mouse models
      with mutations in the murine genes are of limited use to test and further
      optimize human specific AONs in vivo. To address this we have generated the
      del52hDMD/mdx mouse. This model carries both murine and human DMD genes. However,
      mouse dystrophin expression is abolished due to a stop mutation in exon 23, while
      the expression of human dystrophin is abolished due to a deletion of exon 52. The
      del52hDMD/mdx model, like mdx, shows signs of muscle dystrophy on a histological
      level and phenotypically mild functional impairment. Local administration of
      human specific vivo morpholinos induces exon skipping and dystrophin restoration
      in these mice. Depending on the number of mismatches, occasional skipping of the
      murine Dmd gene, albeit at low levels, could be observed. Unlike previous models,
      the del52hDMD/mdx model enables the in vivo analysis of human specific AONs
      targeting exon 51 or exon 53 on RNA and protein level and muscle quality and
      function. Therefore, it will be a valuable tool for optimizing human specific
      AONs and genome editing approaches for DMD.

PMID- 29466449
TI  - Nitric oxide mediates antimicrobial peptide gene expression by activating
      eicosanoid signaling.
AB  - Nitric oxide (NO) mediates both cellular and humoral immune responses in insects.
      Its mediation of cellular immune responses uses eicosanoids as a downstream
      signal. However, the cross-talk with two immune mediators was not known in
      humoral immune responses. This study focuses on cross-talk between two immune
      mediators in inducing gene expression of anti-microbial peptides (AMPs) of a
      lepidopteran insect, Spodoptera exigua. Up-regulation of eight AMPs was observed
      in S. exigua against bacterial challenge. However, the AMP induction was
      suppressed by injection of an NO synthase inhibitor, L-NAME, while little
      expressional change was observed on injecting its enantiomer, D-NAME. The
      functional association between NO biosynthesis and AMP gene expression was
      further supported by RNA interference (RNAi) against NO synthase (SeNOS), which
      suppressed AMP gene expression under the immune challenge. The AMP induction was
      also mimicked by NO alone because injecting an NO analog, SNAP, without bacterial
      challenge significantly induced the AMP gene expression. Interestingly, an
      eicosanoid biosynthesis inhibitor, dexamethasone (DEX), suppressed the NO
      induction of AMP expression. The inhibitory activity of DEX was reversed by the
      addition of arachidonic acid, a precursor of eicosanoid biosynthesis. AMP
      expression of S. exigua was also controlled by the Toll/IMD signal pathway. The
      RNAi of Toll receptors or Relish suppressed AMP gene expression by suppressing NO
      levels and subsequently reducing PLA2 enzyme activity. These results suggest that
      eicosanoids are a downstream signal of NO mediation of AMP expression against
      bacterial challenge.

PMID- 29466450
TI  - Inclusion of live yeast and mannan-oligosaccharides in high grain-based diets for
      sheep: Ruminal parameters, inflammatory response and rumen morphology.
AB  - The objective of this study was to evaluate the effects of dietary
      supplementation with live yeast (Saccharomyces cerevisiae), mannan
      oligosaccharides and the combination of these additives on the inflammatory
      response, ruminal parameters and rumen morphology of sheep fed a high grain-based
      diet. Thirty-Two Dorper x Santa Ines crossbred lambs with an average weight of
      24+/-2 kg were distributed in a completely randomized design. The animals were
      housed in individual stalls and fed ad libitum. Diet treatments were: Control
      (without additive); LY (2 g/kg DM of live yeast, Saccharomyces cerevisiae), MOS
      (2 g/kg DM of mannan-oligosaccharides) and LY+MOS (2 g/kg DM of LY + 2 g/kg DM of
      MOS). The experiment lasted 42 days. The supplementation with MOS alone and the
      additives combination resulted in increased ruminal pH (P<0.01), while the total
      concentrations of short chain fatty acids (SCFA) in the rumen were higher
      (P<0.05) only in the diets with LY and MOS. Ammonia (NH3) concentration in the
      rumen decreased (P<0.04) with the additives usage. Diets with LY, MOS and with
      additives combination reduced (P<0.01) the levels of lipopolysaccharides (LPS) in
      the plasma with values of 0.46; 0.44 and 0.04 EU/mL, respectively when compared
      to the control (0.93 EU/mL). MOS and LY+MOS treatments had reduced stratum
      corneum thickness (P<0.01) in comparison to the control treatment. The total
      thickness of ruminal epithelium was lower with the addition of MOS in the diet
      (P<0.03) than with LY additive. The incidence and severity of hepatic abscesses
      in animals whose diet was supplemented with LY and LY+MOS was lower (P<0.05) than
      in animals fed the control diet. The use of LY, MOS and LY+MOS in the high
      concentrate diets for sheep reduced NH3 concentrations and LPS translocation into
      the bloodstream. Diets containing MOS and LY+MOS enhanced the health of the
      ruminal epithelium by reducing the thickness of the stratum corneum, and diets
      containing LY and LY+MOS decreased the incidence and severity of hepatic
      abscesses.

PMID- 29466451
TI  - Implementing a novel movement-based approach to inferring parturition and neonate
      caribou calf survival.
AB  - In ungulates, parturition is correlated with a reduction in movement rate. With
      advances in movement-based technologies comes an opportunity to develop new
      techniques to assess reproduction in wild ungulates that are less invasive and
      reduce biases. DeMars et al. (2013, Ecology and Evolution 3:4149-4160) proposed
      two promising new methods (individual- and population-based; the DeMars model)
      that use GPS inter-fix step length of adult female caribou (Rangifer tarandus
      caribou) to infer parturition and neonate survival. Our objective was to apply
      the DeMars model to caribou populations that may violate model assumptions for
      retrospective analysis of parturition and calf survival. We extended the use of
      the DeMars model after assigning parturition and calf mortality status by
      examining herd-wide distributions of parturition date, calf mortality date, and
      survival. We used the DeMars model to estimate parturition and calf mortality
      events and compared them with the known parturition and calf mortality events
      from collared adult females (n = 19). We also used the DeMars model to estimate
      parturition and calf mortality events for collared female caribou with unknown
      parturition and calf mortality events (n = 43) and instead derived herd-wide
      estimates of calf survival as well as distributions of parturition and calf
      mortality dates and compared them to herd-wide estimates generated from calves
      fitted with VHF collars (n = 134). For our data, the individual-based method was
      effective at predicting calf mortality, but was not effective at predicting
      parturition. The population-based method was more effective at predicting
      parturition but was not effective at predicting calf mortality. At the herd
      level, the predicted distributions of parturition date from both methods differed
      from each other and from the distribution derived from the parturition dates of
      VHF-collared calves (log-ranked test: chi2 = 40.5, df = 2, p < 0.01). The
      predicted distributions of calf mortality dates from both methods were similar to
      the observed distribution derived from VHF-collared calves. Both methods
      underestimated herd-wide calf survival based on VHF-collared calves, however, a
      combination of the individual- and population-based methods produced herd-wide
      survival estimates similar to estimates generated from collared calves. The
      limitations we experienced when applying the DeMars model could result from the
      shortcomings in our data violating model assumptions. However despite the
      differences in our caribou systems, with proper validation techniques the
      framework in the DeMars model is sufficient to make inferences on parturition and
      calf mortality.

PMID- 29466452
TI  - Self-compassion moderates the perfectionism and depression link in both
      adolescence and adulthood.
AB  - BACKGROUND: Psychological practitioners often seek to directly change the form or
      frequency of clients' maladaptive perfectionist thoughts, because such thoughts
      predict future depression. Indirect strategies, such as self-compassion
      interventions, that seek to change clients' relationships to difficult thoughts,
      rather than trying to change the thoughts directly could be just as effective.
      This study aimed to investigate whether self-compassion moderated, or weakened,
      the relationship between high perfectionism and high depression symptoms in both
      adolescence and adulthood. METHODS: The present study utilised anonymous self
      report questionnaires to assess maladaptive perfectionism, depression, and self
      compassion across two samples covering much of the lifespan. Questionnaires were
      administered in a high school setting for the adolescent sample (Study 1, Mage =
      14.1 years, n = 541), and advertised through university and widely online to
      attract a convenience sample of adults (Study 2, Mage = 25.22 years, n = 515).
      RESULTS: Moderation analyses revealed that self-compassion reduced the strength
      of relationship between maladaptive perfectionism and depression in our
      adolescent Study 1 (beta = -.15, p < .001, R2 = .021.) and our adult study 2
      (beta = -.14, p < .001, R2 = .020). LIMITATIONS: Cross-sectional self-reported
      data restricts the application of causal conclusions and also relies on accurate
      self-awareness and willingness to respond to questionnaire openly. CONCLUSIONS:
      The replication of this finding in two samples and across different age
      appropriate measures suggests that self-compassion does moderate the link between
      perfectionism and depression. Self-compassion interventions may be a useful way
      to undermine the effects of maladaptive perfectionism, but future experimental or
      intervention research is needed to fully assess this important possibility.

PMID- 29466453
TI  - Palladium nanoparticle-decorated reduced graphene oxide sheets synthesized using
      Ficus carica fruit extract: A catalyst for Suzuki cross-coupling reactions.
AB  - We present a biogenic method for the synthesis of palladium nanoparticle (PdNP)
      modified by reducing graphene oxide sheets (rGO) in a one-pot strategy using
      Ficus carica fruit juice as the reducing agent. The synthesized material was well
      characterized by morphological and structural analyses, including, Ultraviolet
      Visible spectroscopy (UV-Vis), X-ray diffraction (XRD), Fourier transform
      infrared spectroscopy (FT-IR) and Transmission Electron Microscopy (TEM) and
      Raman spectroscopy. The results revealed that the PdNP modified GO are spherical
      in shape and estimated to be a dimension of ~0.16 nm. The PdNP/graphene exhibits
      a great catalytic activity in Suzuki cross-coupling reactions for the synthesis
      of biaryl compounds with various substrates under both aqueous and aerobic
      conditions. The catalyst can be recovered easily and is suitable for repeated use
      because it retains its original catalytic activity. The PdNP/rGO catalyst
      synthesized by an eco-friendly protocol was used for the Suzuki coupling
      reactions. The method offers a mild and effective substitute to the existing
      methods and may significantly contribute to green chemistry.

PMID- 29466454
TI  - Interaction between FKBP5 variability and recent life events in the anxiety
      spectrum: Evidence for the differential susceptibility model.
AB  - BACKGROUND: Gene-environment interaction (GxE) research has highlighted the
      importance of investigating the FK506 binding protein 51 (FKBP5) gene as a
      sensitivity gene. However, previous GxE studies with FKBP5 have not measured the
      full environmental spectrum or applied statistical tests to discern whether the
      GxE interaction fits better with the differential-susceptibility or diathesis
      stress hypotheses. This study examined whether single nucleotide polymorphisms
      (SNPs) on FKBP5 gene moderate the association of positive and negative recent
      life events (LEs) with depressive symptoms, state-anxiety, neuroticism, and
      social anxiety traits. METHODS: A total of 86 nonclinical young adults were
      administered psychological measures and were genotyped for five FKBP5 SNPs
      (rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916). RESULTS: Regression
      analyses indicated significant GxE interactions for social anxiety and
      neuroticism. The interactions predicting neuroticism fit different models for
      different SNPs, although the overall effect indicated by the haplotype was
      consistent with the differential-susceptibility hypothesis: the risk-haplotype
      group presented higher neuroticism in the presence of more negative LEs and lower
      neuroticism in the presence of more positive LEs. The GxE interactions for social
      anxiety were consistent with the diathesis-stress model. The lack of significance
      in the for-better side for social anxiety might be related to the fact that it
      mapped onto low extraversion, which is associated with a lower permeability to
      positive experiences. DISCUSSION: Findings underscore the importance of testing
      the differential-susceptibility model in relation to FKBP5 to adequately
      characterize its role in healthy and pathological developmental processes.

PMID- 29466455
TI  - A pneumatic Bionic Voice prosthesis-Pre-clinical trials of controlling the voice
      onset and offset.
AB  - Despite emergent progress in many fields of bionics, a functional Bionic Voice
      prosthesis for laryngectomy patients (larynx amputees) has not yet been achieved,
      leading to a lifetime of vocal disability for these patients. This study
      introduces a novel framework of Pneumatic Bionic Voice Prostheses as an
      electronic adaptation of the Pneumatic Artificial Larynx (PAL) device. The PAL is
      a non-invasive mechanical voice source, driven exclusively by respiration with an
      exceptionally high voice quality, comparable to the existing gold standard of
      Tracheoesophageal (TE) voice prosthesis. Following PAL design closely as the
      reference, Pneumatic Bionic Voice Prostheses seem to have a strong potential to
      substitute the existing gold standard by generating a similar voice quality while
      remaining non-invasive and non-surgical. This paper designs the first Pneumatic
      Bionic Voice prosthesis and evaluates its onset and offset control against the
      PAL device through pre-clinical trials on one laryngectomy patient. The
      evaluation on a database of more than five hours of continuous/isolated speech
      recordings shows a close match between the onset/offset control of the Pneumatic
      Bionic Voice and the PAL with an accuracy of 98.45 +/-0.54%. When implemented in
      real-time, the Pneumatic Bionic Voice prosthesis controller has an average
      onset/offset delay of 10 milliseconds compared to the PAL. Hence it addresses a
      major disadvantage of previous electronic voice prostheses, including myoelectric
      Bionic Voice, in meeting the short time-frames of controlling the onset/offset of
      the voice in continuous speech.

PMID- 29466456
TI  - HMP-1/alpha-catenin promotes junctional mechanical integrity during
      morphogenesis.
AB  - Adherens junctions (AJs) are key structures regulating tissue integrity and
      maintaining adhesion between cells. During morphogenesis, junctional proteins
      cooperate closely with the actomyosin network to drive cell movement and shape
      changes. How the junctions integrate the mechanical forces in space and in time
      during an in vivo morphogenetic event is still largely unknown, due to a lack of
      quantitative data. To address this issue, we inserted a functional Fluorescence
      Resonance Energy Transfer (FRET)-based force biosensor within HMP-1/alpha-catenin
      of Caenorhabditis elegans. We find that the tension exerted on HMP-1 has a cell
      specific distribution, is actomyosin-dependent, but is regulated differently from
      the tension on the actin cortex during embryonic elongation. By using time-lapse
      analysis of mutants and tissue-specific rescue experiments, we confirm the role
      of VAB-9/Claudin as an actin bundle anchor. Nevertheless, the tension exerted on
      HMP-1 did not increase in the absence of VAB-9/Claudin, suggesting that HMP-1
      activity is not upregulated to compensate for loss of VAB-9. Our data indicate
      that HMP-1 does not modulate HMR-1/E-cadherin turnover, is required to recruit
      junctional actin but not stress fiber-like actin bundles. Altogether, our data
      suggest that HMP-1/alpha-catenin acts to promote the mechanical integrity of
      adherens junctions.

PMID- 29466457
TI  - Far-UVC light prevents MRSA infection of superficial wounds in vivo.
AB  - BACKGROUND: Prevention of superficial surgical wound infections from drug
      resistant bacteria such as methicillin resistant Staphylococcus aureus (MRSA)
      currently present major health care challenges. The majority of surgical site
      infections (SSI) are believed to be caused by airborne transmission of bacteria
      alighting onto the wound during surgical procedures. We have previously shown
      that far-ultraviolet C light in the wavelength range of 207-222 nm is
      significantly harmful to bacteria, but without damaging mammalian cells and
      tissues. It is important that the lamp be fitted with a filter to remove light
      emitted at wavelengths longer than 230 nm which are harmful. AIMS: Using a
      hairless mouse model of infection of superficial wounds, here we tested the
      hypothesis that 222-nm light kills MRSA alighting onto a superficial skin
      incisions as efficiently as typical germicidal light (254 nm), but without
      inducing skin damage. METHODS: To simulate the scenario wherein incisions are
      infected during surgical procedures as pathogens in the room alight on a wound,
      MRSA was spread on a defined area of the mouse dorsal skin; the infected skin was
      then exposed to UVC light (222 nm or 254 nm) followed by a superficial incision
      within the defined area, which was immediately sutured. Two and seven days post
      procedure, bactericidal efficacy was measured as MRSA colony formation unit (CFU)
      per gram of harvested skin whereas fixed samples were used to assess skin damage
      measured in terms of epidermal thickness and DNA photodamage. RESULTS: In the
      circumstance of superficial incisions infected with bacteria alighting onto the
      wound, 222-nm light showed the same bactericidal properties of 254-nm light but
      without the associated skin damage. CONCLUSIONS: Being safe for patient and
      hospital staff, our results suggested that far-UVC light (222 nm) might be a
      convenient approach to prevent transmission of drug-resistant infectious agents
      in the clinical setting.

PMID- 29466458
TI  - Flogging tired horses: Who wants whipping and who would walk away if whipping
      horses were withheld?
AB  - Recent studies have cast doubt on the effectiveness of whipping horses during
      races and this has led to questions concerning its continuing justification.
      Furthermore, it has been argued that whipping tired horses in racing is the most
      televised form of violence to animals. The present study used de-identified data
      from a recent independent Australian poll (n = 1,533) to characterise the 26% of
      respondents (113 females and 271 males) who support the whipping of racehorses
      and the 10% of racing enthusiasts in the sample (44 females and 63 males) who
      would stop watching races and betting on them if whipping were banned. Logistic
      regression models examining associations between age, gender, and income level of
      respondents demonstrated that those who support racehorse whipping are
      significantly more likely to be male. Among racing enthusiasts who would stop
      watching races and betting on them if whipping were banned, those in the lowest
      income bracket were over-represented. The more frequently respondents attended
      races or gambled on them, the more likely they were to agree that horses should
      be hit with a whip during the normal course of a race. These findings align with
      previous studies of violence among men and women but may also be attributed to
      male support of traditional gambling practices. Globally, racing organisations
      may consider the findings of the present study helpful in their deliberations on
      the merits of continuing the practice of whipping tired horses in the name of
      sport. The study might also provide important data for stakeholders who demand
      that it continues.

PMID- 29466459
TI  - Global influenza seasonality to inform country-level vaccine programs: An
      analysis of WHO FluNet influenza surveillance data between 2011 and 2016.
AB  - By analyzing publicly available surveillance data from 2011-2016, we produced
      country-specific estimates of seasonal influenza activity for 118 countries in
      the six World Health Organization regions. Overall, the average country influenza
      activity period was 4.7 months. Our analysis characterized 100 countries (85%)
      with one influenza peak season, 13 (11%) with two influenza peak seasons, and
      five (4%) with year-round influenza activity. Surveillance data were limited for
      many countries. These data provide national estimates of influenza activity,
      which may guide planning for influenza vaccination implementation, program timing
      and duration, and policy development.

PMID- 29466460
TI  - High intra-specific variation in avian body condition responses to climate limits
      generalisation across species.
AB  - It is generally assumed that populations of a species will have similar responses
      to climate change, and thereby that a single value of sensitivity will reflect
      species-specific responses. However, this assumption is rarely systematically
      tested. High intraspecific variation will have consequences for identifying
      species- or population-level traits that can predict differences in sensitivity,
      which in turn can affect the reliability of projections of future climate change
      impacts. We investigate avian body condition responses to changes in six climatic
      variables and how consistent and generalisable these responses are both across
      and within species, using 21 years of data from 46 common passerines across 80
      Dutch sites. We show that body condition decreases with warmer spring/early
      summer temperatures and increases with higher humidity, but other climate
      variables do not show consistent trends across species. In the future, body
      condition is projected to decrease by 2050, mainly driven by temperature effects.
      Strikingly, populations of the same species generally responded just as
      differently as populations of different species implying that a single species
      signal is not meaningful. Consequently, species-level traits did not explain
      interspecific differences in sensitivities, rather population-level traits were
      more important. The absence of a clear species signal in body condition responses
      implies that generalisation and identifying species for conservation
      prioritisation is problematic, which sharply contrasts conclusions of previous
      studies on the climate sensitivity of phenology.

PMID- 29466461
TI  - A new look at the decomposition of agricultural productivity growth incorporating
      weather effects.
AB  - Random fluctuations in temperature and precipitation have substantial impacts on
      agricultural output. However, the contribution of these changing configurations
      in weather to total factor productivity (TFP) growth has not been addressed
      explicitly in econometric analyses. Thus, the key objective of this study is to
      quantify and to investigate the role of changing weather patterns in explaining
      yearly fluctuations in TFP. For this purpose, we define TFP to be a measure of
      total output divided by a measure of total input. We estimate a stochastic
      production frontier model using U.S. state-level agricultural data incorporating
      growing season temperature and precipitation, and intra-annual standard
      deviations of temperature and precipitation for the period 1960-2004. We use the
      estimated parameters of the model to compute a TFP index that has good axiomatic
      properties. We then decompose TFP growth in each state into weather effects,
      technological progress, technical efficiency, and scale-mix efficiency changes.
      This approach improves our understanding of the role of different components of
      TFP in agricultural productivity growth. We find that annual TFP growth averaged
      1.56% between 1960 and 2004. Moreover, we observe substantial heterogeneity in
      weather effects across states and over time.

PMID- 29466462
TI  - Reduced NK cell IFN-gamma secretion and psychological stress are independently
      associated with herpes zoster.
AB  - The pathogenesis of herpes zoster is closely linked to reduced varicella-zoster
      virus-specific cell-mediated immunity. However, little is known about the
      interplay between natural killer cells and psychological stress in the
      pathogenesis of herpes zoster. This study aimed to investigate possible
      associations among natural killer cells, T cells and psychological stress in
      herpes zoster. Interferon-gamma secretion from natural killer cell, psychological
      stress events, stress cognition scale scores and cytomegalovirus-specific cell
      mediated immunity were compared between 44 patients with herpes zoster and 44 age
      and gender-matched control subjects. A significantly lower median level of
      interferon-gamma secreted by natural killer cells was observed in patients with a
      recent diagnosis of herpes zoster than in control subjects (582.7 pg/ml vs. 1783
      pg/ml; P = 0.004), whereas cytomegalovirus-specific cell-mediated immunity was
      not associated with herpes zoster. Psychological stress events and high stress
      cognition scale scores were significantly associated in patients with herpes
      zoster (P<0.001 and P = 0.037, respectively). However, reduced interferon-gamma
      secretion from natural killer cell and psychological stress were not associated.
      In conclusion, patients with a recent diagnosis of herpes zoster display reduced
      interferon-gamma secretion from natural killer cells and frequent previous
      psychological stress events compared with controls. However, reduced natural
      killer cell activity is not an immunological mediator between psychological
      stress and herpes zoster.

PMID- 29466463
TI  - Unmet needs and service satisfaction of victim support for the direct and
      indirect victims of serious violence: Results from a cross-sectional survey in
      Taiwan.
AB  - Victim support services, in mature societies, aim to help victims recover after
      suffering a traumatic event. The effectiveness of victim support has
      traditionally been evaluated through rates of service utilization and incidence
      of psychopathology such as posttraumatic stress disorder. The current study,
      instead, inquires into service users' unmet needs and satisfaction, and
      identifies factors that mediate such subjective measures, using data from a
      national cross-sectional survey on victims and surviving families of violent
      crime in Taiwan in 2011. The results reveal: 1) a gap between available and
      expected services, and 2) a correlation between service utilization and
      satisfaction, both consistent with previous studies. In addition, the current
      study identifies unsatisfied service users: They are homicidally bereaved, live
      with their spouse, suffer from post-crime financial distress and are still
      waiting for a court verdict on the incident. Victim support that helps victims
      heal through tailored services incorporating relationship counseling is proposed.

PMID- 29466464
TI  - Factors that enable or limit the sustained use of improved firewood cookstoves:
      Qualitative findings eight years after an intervention in rural Mexico.
AB  - OBJECTIVE: The aim of this study was to analyze the factors enabling/limiting the
      use of improved cookstoves among rural fuel wood users from one mestizo and two
      indigenous communities eight years after an intervention in the state of
      Michoacan, in Mexico. METHODS: A qualitative study with an ethnographic
      perspective was conducted in 2013/2014 based on 62 interviews with women who had
      participated in an improved firewood cookstove program in 2005. Thematic
      qualitative content analysis was performed. RESULTS: Very few women from the
      indigenous communities were using the improved cookstove at the time of the
      study; the majority had dismantled or had ceased using it; whereas most of those
      from the mestizo community were using it for all of their cooking activities. In
      the indigenous communities, characterized by extended families, uptake of new
      technology was limited by traditional routine practices, rearrangement of rooms
      in the house, attachment to the traditional stove, a low- or non-risk perception
      of woodsmoke; gender relations, insufficient training, non-compliance with
      program recommendations and design-related aspects. Conversely, in the mestizo
      community, the uptake of the improved cookstove was favored by routine cooking
      practices in a nuclear family, a previous use of a raised cookstove and social
      representations on the health-disease-death effects of woodsmoke vs. the health
      benefits of cooking with improved stoves. The sociocultural dimension of
      communities and the cookstove design are aspects that either favor or limit the
      use of improved cookstoves in indigenous and mestizo populations. CONCLUSIONS:
      Effective cookstove programs must take these elements into account from their
      early planning stages, and blend them into implementation and follow-up. Project
      communication, training and differentiated follow-up activities ensuring the
      operation and maintenance of the cookstove, should be designed according to the
      specific needs and traditions of each community; they should be based on the
      preferences and needs of the users.

PMID- 29466465
TI  - Analysis of the genetic basis of plant height-related traits in response to
      ethylene by QTL mapping in maize (Zea mays L.).
AB  - Ethylene (ET) is critical importance in the growth, development, and stress
      responses of plants. Plant hormonal stress responses have been extensively
      studied, however, the role of ET in plant growth, especially plant height (PH)
      remains unclear. Understanding the genetic control for PH in response to ET will
      provide insights into the regulation of maize development. To clarify the genetic
      basis of PH-related traits of maize in response to ET, we mapped QTLs for PH, ear
      height (EH), and internode length above the uppermost ear (ILAU) in two
      recombinant inbred line (RIL) populations of Zea mays after ET treatment and in
      an untreated control (CK) group. Sixty QTLs for the three traits were identified.
      Twenty-two QTLs were simultaneously detected under both ET treatment and
      untreated control, and five QTLs were detected at two geographic locations under
      ET treatment only. Individual QTL can be explained 3.87-17.71% of the phenotypic
      variance. One QTL (q2PH9-1, q1PH9, q1EH9/q1ILAU9-1, q2ILAU9, and q2EH9) for the
      measured traits (PH, EH, ILAU) was consistent across both populations. Two QTLs
      (q2PH2-5, q2ILAU2-2, q1PH2-2, and q1ILAU2-2; q1PH8-1, q1EH8-1, q2PH8-1) were
      identified for up to two traits in both locations and populations under both ET
      treatment and untreated control. These consistent and stable regions are
      important QTLs of potential hot spots for PH, ear height (EH), and internode
      length above the uppermost ear (ILAU) response to ET in maize; therefore, QTL
      fine-mapping and putative candidate genes validation should enable the cloning of
      PH, EH, and ILAU related genes to ET response. These results will be valuable for
      further fine-mapping and quantitative trait nucleotides (QTNs) determination, and
      elucidate the underlying molecular mechanisms of ET responses in maize.

PMID- 29466466
TI  - Family history and obesity in youth, their effect on acylcarnitine/aminoacids
      metabolomics and non-alcoholic fatty liver disease (NAFLD). Structural equation
      modeling approach.
AB  - BACKGROUND: Structural equation modeling (SEM) can help understanding complex
      functional relationships among obesity, non-alcoholic fatty liver disease
      (NAFLD), family history of obesity, targeted metabolomics and pro-inflammatory
      markers. We tested two hypotheses: 1) If obesity precedes an excess of free fatty
      acids that increase oxidative stress and mitochondrial dysfunction, there would
      be an increase of serum acylcarnitines, amino acids and cytokines in obese
      subjects. Acylcarnitines would be related to non-alcoholic fatty disease that
      will induce insulin resistance. 2) If a positive family history of obesity and
      type 2 diabetes are the major determinants of the metabolomic profile, there
      would be higher concentration of amino acids and acylcarnitines in patients with
      this background that will induce obesity and NAFLD which in turn will induce
      insulin resistance. METHODS/RESULTS: 137 normoglycemic subjects, mean age (SD) of
      30.61 (8.6) years divided in three groups: BMI<25 with absence of NAFLD (G1), n =
      82; BMI>30 with absence of NAFLD (G2), n = 24; and BMI>30 with NAFLD (G3), n =
      31. Family history of obesity (any) was present in 53%. Both models were adjusted
      in SEM. Family history of obesity predicted obesity but could not predict
      acylcarnitines and amino acid concentrations (effect size <0.2), but did predict
      obesity phenotype. CONCLUSION: Family history of obesity is the major predictor
      of obesity, and the metabolic abnormalities on amino acids, acylcarnitines,
      inflammation, insulin resistance, and NAFLD.

PMID- 29466467
TI  - Fragments of peer review: A quantitative analysis of the literature (1969-2015).
AB  - This paper examines research on peer review between 1969 and 2015 by looking at
      records indexed from the Scopus database. Although it is often argued that peer
      review has been poorly investigated, we found that the number of publications in
      this field doubled from 2005. A half of this work was indexed as research
      articles, a third as editorial notes and literature reviews and the rest were
      book chapters or letters. We identified the most prolific and influential
      scholars, the most cited publications and the most important journals in the
      field. Co-authorship network analysis showed that research on peer review is
      fragmented, with the largest group of co-authors including only 2.1% of the whole
      community. Co-citation network analysis indicated a fragmented structure also in
      terms of knowledge. This shows that despite its central role in research, peer
      review has been examined only through small-scale research projects. Our findings
      would suggest that there is need to encourage collaboration and knowledge sharing
      across different research communities.

PMID- 29466468
TI  - Fluorescent single-stranded DNA-binding protein from Plasmodium falciparum as a
      biosensor for single-stranded DNA.
AB  - Single-stranded DNA (ssDNA) is a product of many cellular processes that involve
      double-stranded DNA, for example during DNA replication and repair, and is formed
      transiently in many others. Measurement of ssDNA formation is fundamental for
      understanding many such processes. The availability of a fluorescent biosensor
      for the determination of single-stranded DNA provides an important route to
      achieve this. Single-stranded DNA binding proteins (SSBs) protect ssDNA from
      degradation, but can be displaced to allow processing of the ssDNA. Their tight
      binding of ssDNA means that they are very good candidates for the development of
      a biosensor. Previously, the single stranded DNA binding protein from Escherichia
      coli, labeled with a fluorophore, (DCC-EcSSB) was developed and used for this
      purpose. However, the multiple binding modes of this protein meant that
      interpretation of DCC-EcSSB fluorescence was potentially complex in terms of
      determining the amount of ssDNA. Here, we present an improved biosensor,
      developed using the tetrameric SSB from Plasmodium falciparum as a new scaffold
      for fluorophore attachment. Each subunit of this tetrameric SSB was labeled with
      a diethylaminocoumarin fluorophore at a single site on its surface, such that
      there is a very large, 20-fold, fluorescence increase when it binds to ssDNA.
      This adduct can be used as a biosensor to report ssDNA formation. Because SSB
      from this organism has a single mode of binding ssDNA, namely 65-70 bases per
      tetramer, over a wide range of conditions, the fluorescent SSB allows simple
      quantitation of ssDNA. The binding is fast, possibly diffusion controlled, and
      tight (dissociation constant for DCC-PfSSB <5 pM). Its suitability for real-time
      assays of ssDNA formation was demonstrated by measurement of AddAB helicase
      activity, unwinding double-stranded DNA.

PMID- 29466469
TI  - ERP evidence for consumer evaluation of copycat brands.
AB  - Copycat brands mimic brand leaders to free ride on the latter's equity. However,
      little is known regarding if and how consumers confuse copycat as leading brand
      in purchasing. In this study, we applied a word-pair evaluation paradigm in which
      the first word was a brand name (copycat vs. normal brand both similar with a
      leading brand in category), followed by a product name (near vs. far from the
      leading brand's category). Behavioral results showed that, when the product is
      near the leader's category, the copycat strategy (CN) was more preferred compared
      to the normal brand (NN) but not different in the far product condition (CF and
      NF). Event-related potential (ERP) data provided further insight into the
      mechanism. The N400 amplitude elicited by the CN condition was significantly
      smaller than NN. However, when products are far from the leader's category, there
      was no significant difference in N400 amplitudes. For the late positive component
      (LPC), the CN gave rise to a larger amplitude than the CF. The N400 amplitude was
      suggested to reflect the categorization process, and the LPC demonstrated the
      recollection process in long-term memory. These findings imply that the copycat
      brand strategy is generally only effective when products are within the category
      of the leading brand, which offers important implications for marketing
      practices.

PMID- 29466470
TI  - Early intervention for subthreshold panic disorder in the Netherlands: A model
      based economic evaluation from a societal perspective.
AB  - BACKGROUND: Panic disorder (PD) is associated with impaired functioning and
      reduced quality of life. In the Netherlands, almost 2% of the population
      experiences clinically relevant panic symptoms without meeting the diagnostic
      criteria for PD, which is referred to as subthreshold PD (STHPD). Evidence
      suggests that subthreshold mental disorders may have a similar impact on quality
      of life and functioning in comparison with full-blown mental disorders, which
      draws attention to the need for interventions for STHPD. These interventions are
      currently not systematically provided in clinical practice. This study aims to
      investigate the population cost-effectiveness of adding a CBT-based early
      intervention for adults with STHPD to the existing health care for people with PD
      in the Netherlands. METHODS: A health-economic Markov model was constructed in
      order to compare quality adjusted life-years (QALYs) and societal costs of adding
      an early intervention to usual care for PD. The model compares usual care with an
      alternative program in which usual care is supplemented with a CBT-based early
      intervention. Input parameters for the model were derived from national sources
      and published literature where possible, and based on expert opinion otherwise.
      Probabilistic and deterministic sensitivity analyses were conducted to evaluate
      the uncertainty of the model input parameters. RESULTS: On average, the added CBT
      based early intervention was dominant in comparison with usual care, meaning that
      the early intervention yielded more QALYs at lower costs. At a willingness-to-pay
      threshold of ?20,000 per QALY, the cost-effectiveness probability of the added
      early intervention was 98%. Sensitivity analyses showed that the results were
      robust. CONCLUSIONS: This study showed that offering an early intervention in
      addition to usual care for PD is potentially cost-effective, but it should be
      further investigated to what extent trial results can be extrapolated to the
      level of the population before such interventions are implemented on a large
      scale.

PMID- 29466471
TI  - Correction: Characterizing RecA-Independent Induction of Shiga toxin2-Encoding
      Phages by EDTA Treatment.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0032393.].

PMID- 29466472
TI  - When listening to rain sounds boosts arithmetic ability.
AB  - Studies in the literature have provided conflicting evidence about the effects of
      background noise or music on concurrent cognitive tasks. Some studies have shown
      a detrimental effect, while others have shown a beneficial effect of background
      auditory stimuli. The aim of this study was to investigate the influence of
      agitating, happy or touching music, as opposed to environmental sounds or
      silence, on the ability of non-musician subjects to perform arithmetic
      operations. Fifty university students (25 women and 25 men, 25 introverts and 25
      extroverts) volunteered for the study. The participants were administered 180
      easy or difficult arithmetic operations (division, multiplication, subtraction
      and addition) while listening to heavy rain sounds, silence or classical music.
      Silence was detrimental when participants were faced with difficult arithmetic
      operations, as it was associated with significantly worse accuracy and slower RTs
      than music or rain sound conditions. This finding suggests that the benefit of
      background stimulation was not music-specific but possibly due to an enhanced
      cerebral alertness level induced by the auditory stimulation. Introverts were
      always faster than extroverts in solving mathematical problems, except when the
      latter performed calculations accompanied by the sound of heavy rain, a condition
      that made them as fast as introverts. While the background auditory stimuli had
      no effect on the arithmetic ability of either group in the easy condition, it
      strongly affected extroverts in the difficult condition, with RTs being faster
      during agitating or joyful music as well as rain sounds, compared to the silent
      condition. For introverts, agitating music was associated with faster response
      times than the silent condition. This group difference may be explained on the
      basis of the notion that introverts have a generally higher arousal level
      compared to extroverts and would therefore benefit less from the background
      auditory stimuli.

PMID- 29466473
TI  - Combined epidural-general anesthesia was associated with lower risk of
      postoperative complications in patients undergoing open abdominal surgery for
      pheochromocytoma: A retrospective cohort study.
AB  - BACKGROUND: Current evidences show that regional anesthesia is associated with
      decreased risk of complications after major surgery. However, the effects of
      combined regional-general anesthesia remain controversial. The purpose of our
      study was to analyze the impact of anesthesia (combined epidural-general
      anesthesia vs. general anesthesia) on the risk of postoperative complications in
      patients undergoing open surgery for pheochromocytoma. METHODS: This was a
      retrospective cohort study. 146 patients who underwent open surgery for
      pheochromocytoma (100 received combined epidural-general anesthesia and 46
      received general anesthesia) in Peking University First Hospital from January 1,
      2002 to December 31, 2015 were enrolled. The primary outcome was the occurrence
      of postoperative complications during hospital stay after surgery. Multivariate
      Logistic regression models were used to analyze the association between the
      choice of anesthetic method and the risk of postoperative complications. RESULTS:
      17 (11.6%) patients developed complications during postoperative hospital stay.
      The incidence of postoperative complications was lower in patients with combined
      epidural-general anesthesia than in those with general anesthesia (6% [6/100] vs.
      23.9% [11/46], P = 0.006). Multivariate Logistic regression analysis showed that
      use of combined epidural-general anesthesia (OR 0.219, 95% CI 0.065-0.741; P =
      0.015) was associated with lower risk, whereas male gender (OR 5.213, 95% CI
      1.283-21.177; P = 0.021) and perioperative blood transfusion (OR 25.879; 95% CI
      3.130-213.961; P = 0.003) were associated with higher risk of postoperative
      complications. CONCLUSIONS: For patients undergoing open surgery for
      pheochromocytoma, use of combined epidural-general anesthesia may decrease the
      occurrence of postoperative complications.

PMID- 29466475
TI  - Cost Effectiveness of Arthrocentesis Compared to Conservative Therapy for
      Arthralgia of the Temporomandibular Joint: A Randomized Controlled Trial.
AB  - AIMS: To determine the cost effectiveness and cost utility of arthrocentesis as
      an initial treatment for temporomandibular joint (TMJ) arthralgia compared to
      usual care. METHODS: A two-armed, parallel-design, randomized controlled trial
      (RCT) was conducted in the Netherlands from January 2009 to June 2012 that
      included patients with TMJ arthralgia. Patients were randomly allocated to
      arthrocentesis (n = 40) or usual care (n = 40) for initial treatment.
      Arthrocentesis consisted of rinsing the intra-articular space with isotonic
      saline, and usual care included a soft diet, physical therapy, and splint
      therapy. The duration of the usual care program was 6 weeks, and follow-up was
      conducted 3, 12, and 26 weeks after its completion. Generalized estimated
      equation multivariate models were assessed in order to correct for the dependency
      of repeated measurements in the longitudinal data analysis. An independent
      samples t test was used to compare the arthrocentesis group with the usual care
      group for TMJ pain after 26 weeks. Cost effectiveness (total cost from a societal
      view) was related to TMJ pain (as measured on a visual analog scale [0 to 100
      mm]) and to cost utility (quality-adjusted life years). RESULTS: TMJ pain
      declined more quickly in the arthrocentesis group (n = 36) than in the usual care
      group (n = 36) (regression coefficient beta = -10.76; 95% confidence interval
      [CI] = -17.75 to -3.77; P = .003). The estimated mean total (ie, societal) cost
      over 26 weeks was ?589 (US $795) in the arthrocentesis group and ?1,680 (US
      $2,266) in the usual care group. Arthrocentesis was associated with a lower mean
      cost and better health outcomes than usual care in 98% and 95% of the bootstrap
      simulations, respectively. CONCLUSION: The results of this study suggest that,
      from an economical perspective, arthrocentesis may be superior to usual care for
      the initial treatment of TMJ pain, as it had better health outcomes and lower
      costs than usual care.

PMID- 29466474
TI  - Early measurement of interleukin-10 predicts the absence of CT scan lesions in
      mild traumatic brain injury.
AB  - Traumatic brain injury is a common event where 70%-90% will be classified as mild
      TBI (mTBI). Among these, only 10% will have a brain lesion visible via CT scan. A
      triage biomarker would help clinicians to identify patients with mTBI who are at
      risk of developing a brain lesion and require a CT scan. The brain cells damaged
      by the shearing, tearing and stretching of a TBI event set off inflammation
      cascades. These cause altered concentrations of a high number of both pro
      inflammatory and anti-inflammatory proteins. This study aimed to discover a novel
      diagnostic biomarker of mTBI by investigating a broad panel of inflammation
      biomarkers and their capacity to correctly identify CT-positive and CT-negative
      patients. Patients enrolled in this study had been diagnosed with mTBI, had a GCS
      score of 15 and suffered from at least one clinical symptom. There were nine
      patients in the discovery group, 45 for verification, and 133 mTBI patients from
      two different European sites in the validation cohort. All patients gave blood
      samples, underwent a CT scan and were dichotomised into CT-positive and CT
      negative groups for statistical analyses. The ability of each protein to classify
      patients was evaluated with sensitivity set at 100%. Three of the 92 inflammation
      proteins screened-MCP-1, MIP-1alpha and IL-10 -were further investigated in the
      verification group, and at 100% sensitivity their specificities reached 7%, 0%
      and 31%, respectively. IL-10 was validated on a larger cohort in comparison to
      the most studied mTBI diagnostic triage protein to date, S100B. Levels of both
      proteins were significantly higher in CT-positive than in CT-negative patients (p
      < 0.001). S100B's specificity at 100% sensitivity was 18% (95% CI 10.8-25.2),
      whereas IL-10 reached a specificity of 27% (95% CI 18.9-35.1). These results
      showed that IL-10 might be an interesting and clinically useful diagnostic tool,
      capable of differentiating between CT-positive and CT-negative mTBI patients.

PMID- 29466476
TI  - PD-L1 is a positive prognostic factor in squamous cell carcinoma of the nasal
      vestibule.
AB  - BACKGROUND: Aim was to analyse the role of PD-L1 in squamous cell carcinomas of
      the nasal vestibule. Advanced squamous cell carcinoma of the nasal vestibule is a
      highly aggressive tumour. The role of PD-L1 expression is unclear in this tumour
      type. METHODOLOGY: Forty-six patients diagnosed between 1995 and 2014 were
      analyzed. Baseline characteristics and outcome were correlated to
      immunohistochemical staining of PD-L1. PD-L1 positivity of tumour cells and
      tumour infiltrating immune cells (TIIC) was defined by any staining of more than
      1% of the tumour cells. RESULTS: PD-L1 expression was interpretable in 31 of 46
      patients (67.4%). PD-L1 positivity was present in 14 (45.2%) patients tumour
      cells and 17 (54.8%) patients TIIC. PD-L1 positivity of tumour cells was
      associated with a favourable disease free survival (p=0.019). CONCLUSIONS:
      Positivity for PD-L1 in tumour cells is a prognostic factor in squamous cell
      carcinoma of the nasal vestibule and might enable a patient-tailored treatment.

PMID- 29466477
TI  - mySinusitisCoach: patient empowerment in chronic rhinosinusitis using mobile
      technology.
AB  - Mobile health technology is emerging to take a prominent position in the
      management of chronic diseases. These technologies aim at enhancing patient
      empowerment via education and self-management. To date, of all the different apps
      available for patients with sinus disease, none were developed by medical experts
      dealing with chronic rhinosinusitis (CRS). The European Forum for Research and
      Education in Allergy and Airway diseases (EUFOREA) has undertaken a multi
      stakeholder approach for designing, developing and implementing a tool to support
      CRS patients in monitoring their symptoms and to provide patients with a digital
      support platform containing reliable medical information about their disease and
      treatment options. mySinusitisCoach has been developed by medical experts dealing
      with CRS in close collaboration with patients, primary care physicians and
      community pharmacists, meeting the needs of both patients and health care
      providers. From a research perspective, the generation of real life data will
      help to validate clinical studies, patient stratification and improve
      understanding of the socio-economic impact of CRS, thereby paving the way for
      better treatment strategies.

PMID- 29466478
TI  - The Effect of Ferrous Nano-oxide Particles on Physiological Traits and
      Nutritional Compounds of Soybean ( Glycine max L.) Seed.
AB  - Soybean (Glycine max L.) seed contains amounts of protein, lipid, carbohydrate
      and mineral elements, which protein and lipid have been known as a main part for
      soybean's trade value. In this study, in order to investigate the effect of
      ferrous nano-oxide particles on nutritional compounds of soybean seed, an
      experiment with 5 treatments and 3 replications was conducted as a randomized
      complete block design. Treatments were 5 concentrations of ferrous nano-oxide
      particles including 0, 0.25, 0.5, 0.75 and 1 g L-1 which were sprayed 3 times at
      4 and 8 leaves stage and pod initiation. Lipid and protein contents, fatty acids
      profile, some of mineral elements such as Fe, Mg, Ca and P, chlorophyll a, b and
      total chlorophyll content were determined. Results showed that solution
      containing ferrous nano-oxide particles had significant effect on nutritional
      compounds of soybean seed (P<0.01) compared to control. The highest content of
      lipid and protein (25.4 and %33.8, respectively) observed by applying 0.75 g L-1
      of ferrous nano-oxide and the lowest content was also in control. Changes in the
      trends of fatty acids profile (palmitic, oleic, linoleic and linolenic acids),
      some of mineral elements (Fe, Mg, Ca and P) and chlorophyll contents were similar
      to lipid and protein levels which by increasing in concentration of ferrous nano
      oxide from 0 to 0.75 g L-1 all measured parameters also increased, but reduction
      in all parameters was observed in concentration from 0.75 to 1 g L-1. In
      conclusion, application of 0.75 to 1 g L-1 ferrous nano-oxide had the best effect
      on the nutrient composition of soybean seed.

PMID- 29466479
TI  - Tree community variation in a tropical continental island according to slope
      aspect and human interference.
AB  - Associating description of unrecorded tropical tree community structure to
      sampling approaches that can help determine mechanisms behind floristic variation
      is important to further the comprehension of how plant species coexist at
      tropical forests. Thus, this study had the goals of (i) evaluating tree community
      structure on the continental island of Marambaia (23 degrees 4'37.09"S; 43
      degrees 59'2.15"W) and (ii) testing the prediction that there are local scale
      changes in a tropical tree community structure between slopes facing different
      geographic orientation and with distinct human interference history. We
      established 60 (0.6 ha) sampling units in three different slope sites with
      distinct predominant geographic orientation and human interference. We sampled
      all woody trees with diameter at breast height (dbh) >= 5 cm. We found a total of
      1.170 individuals representing 220 species, 120 genera and 50 families. The
      overall tree community structure and structural descriptors (abundance of
      individuals, basal area, species richness and diversity) varied extensively
      between the sites. The evidence presented here supports that local scale
      topography variations and human interference history can be important factors
      contributing to the known floristic heterogeneity of the Atlantic Rainforest.
      Future work on the study area should focus on disentangling effects from distinct
      causal factors over tree community variation and species occurrence.

PMID- 29466480
TI  - Evaluation of growth performance and gastro-intestinal parameters on the response
      of weaned piglets to dietary organic acids.
AB  - Two experiments (E) were carried out to evaluate the effects of fumaric acid and
      an acidifier blend [composed by calcium formate, calcium lactate and medium-chain
      fatty acids (capric and caprylic)] in piglet diets containing colistin (40 ppm)
      or halquinol (120 ppm) on performance, diarrhea incidence (E1), organs relative
      weight, pH values, intestinal morphometry and microbiota (E2). In E1, 192 and E2,
      24 piglets weaned at 21-day-old were randomly assigned to blocks with 2x2
      factorial arrangement of treatments [absence or presence of fumaric acid x
      absence or presence of acidifier blend], six replicates of eight (E1) and one
      piglet per pen (E2). For E1, the treatments were control (CD): no acidifier
      product + 40 ppm of colistin, FA: fumaric acid in absence of acidifier blend, AB:
      acidifier blend in absence of fumaric acid and, AF+AB: presence of fumaric acid
      and acidifier blend. For E2, the pre-starter I diet were used and the same
      treatments as E1 evaluated. No treatment effects (P>0.05) were observed on
      performance, diarrhea incidence (E1), gut pH values and duodenum morphometry of
      piglets (E2). However, the addition of AB increased (P<0.05) large intestine
      relative weight and, FA addition decreased (P<0.05) pancreas relative weight,
      jejunum villi height and, total coliform and E. coli counts in cecum. The
      inclusion of FA and AB in diets containing colistin or halquinol did not improve
      performance, although FA exerted an inhibitory effect on cecum microbiota.

PMID- 29466481
TI  - Morphological Characterization of Diaphragm in Common Squirrel Monkey (Saimiri
      sciureus).
AB  - The wall of the diaphragm can be affected by congenital or acquired alterations
      which allow the passage of viscera between the abdominal and chest cavities,
      allowing the formation of a diaphragmatic hernia. We characterized morphology and
      performed biometrics of the diaphragm in the common squirrel monkey Saimiri
      sciureus. After fixation, muscle fragments were collected and processed for
      optical microscopy. In this species the diaphragm muscle is attached to the lung
      by phrenopericardial ligament. It is also connected to the liver via the coronary
      and falciform ligaments. The muscle is composed of three segments in total: 1)
      sternal; 2) costal, and 3) a segment consisting of right and left diaphragmatic
      pillars. The anatomical structures analyzed were similar to those reported for
      other mammals. Histological analysis revealed stable, organized muscle fibers
      with alternation of light and dark streaks, indicating transverse striation.

PMID- 29466482
TI  - Shoot and root interference of morning glory on the initial growth of sugarcane.
AB  - Among weeds, morning glories comprise a very important group of climbing plants
      that infest sugarcane crops. The objective of this study was to evaluate the
      shoot and root interference of Merremia cissoides on the initial growth of
      sugarcane cultivar RB 966928. The experiment consisted of five treatment groups:
      (i) sugarcane monocropping, (ii) morning glory monocropping, (iii) sugarcane
      intertwined with morning glory but inseparate boxes, (iv) sugarcane intertwined
      with morning glory in attached boxes and (v) sugarcane with morning glory in
      attached boxes with morning glory prevented from intertwining with the sugarcane.
      The experimental design consisted of randomized blocks with four replicates.
      Merremia cissoides adversely affected the initial growth of the RB 966928
      sugarcane starting at 90 days after transplanting (DAT). This effect increased
      with the time of intercropping, reaching at 180 DAT with a reduction of 57.3% in
      height,15.5% in stalk diameter, 90.4% in leaf areas, 86.6 and 75.2% in stalk and
      leaf dry mass, respectively. These reductions primarily due to the weed
      intertwining with the sugarcane plants because the weed had a physical choking
      and shading effect. This negative effect of morning glory on the sugarcane plants
      increased when they shared the substrate (i.e., when they competed for space and
      water), which also adversely affected weed growth, reducing 50.2% leaf areas and
      42.1% shoot dry mass. The leaf area and the stalk and leaf dry mass of sugarcane
      are the characteristics more sensitive to the weed interference. Thus, both the
      shoot and root of M. cissoides interferes negatively in the growth of sugarcane,
      with the effect proportional to the period of coexistence, highlighting the
      detrimental effect on the stem (greater economic interest), and may also
      compromise the mechanical harvesting of the crop.

PMID- 29466483
TI  - Plant growth, nutrients and potentially toxic elements in leaves of yerba mate
      clones in response to phosphorus in acid soils.
AB  - Native to subtropical region of South America, yerba mate is responsive to P
      under some conditions, but the degree of influence of genetic and soil on the
      growth and composition of the leaf is unknown. The aim of study was to evaluate
      plant growth, nutrients and potentially toxic elements in leaves of yerba mate
      clones in response to P application in acid soils. In greenhouse condition, two
      yerba mate clone seedlings were grown (210 days) in pots, each clone in a
      completely randomized design in factorial scheme (with and without P; four acid
      soils). The elemental composition of leaves and the growth of plants were
      determined. Phosphorus promoted plant growth, but this was not accompanied by
      increased P in leaf tissue in all conditions tested. The P effect on the
      elemental composition varied: decrease/null (N, K, Mg, Mn, Cu, Ni, B, Mo, Al,
      Cd); increase/null (C/N, C, Ca, Fe, V); increase/decrease/null (Zn, Ba, Pb) and;
      null (Cr). The soils affect the elemental composition of the leaves, especially
      Mn, with accumulation greater than 1000 mg kg-1. The Ba, Pb, Al and Zn in the
      leaves varied among clones. Yerba mate response to P was affected by edaphic and
      plant factors.

PMID- 29466484
TI  - The predator Coenosia Attenuata Stein (Diptera, Muscidae) on cultivated plants
      from Brazil.
AB  - Coenosia attenuata Stein (1903) is a predatory fly that is commonly found in
      greenhouses and open fields preying on whiteflies, leafminers, psocopterans and
      other insects. The species is widespread in the Old World and its distribution
      has expanded in recent times to Neotropical countries including Chile, Colombia,
      Costa Rica, Ecuador and Peru. We report here for the first time the presence of
      C. attenuata in Brazil, occurring in different sites in the State of Ceara
      (Northeastern Brazil). Expansion of the distribution range of this muscid to the
      eastern parts of South America opens up the possibility of applying the
      beneficial predator as a biological control agent for protected crops of the
      region.

PMID- 29466485
TI  - Autonomic and Vascular Control in Prehypertensive Subjects with a Family History
      of Arterial Hypertension.
AB  - BACKGROUND: Individuals with a family history of systemic arterial hypertension
      (FHSAH) and / or prehypertension have a higher risk of developing this pathology.
      OBJECTIVE: To evaluate the autonomic and vascular functions of prehypertensive
      patients with FHSAH. METHODS: Twenty-five young volunteers with FHSAH, 14
      normotensive and 11 prehypertensive subjects were submitted to vascular function
      evaluation by forearm vascular conductance(VC) during resting and reactive
      hyperemia (Hokanson(r)) and cardiac and peripheral autonomic modulation,
      quantified, respectively, by spectral analysis of heart rate (ECG) and systolic
      blood pressure (SBP) (FinometerPRO(r)). The transfer function analysis was used
      to measure the gain and response time of baroreflex. The statistical significance
      adopted was p <= 0.05. RESULTS: Pre-hypertensive individuals, in relation to
      normotensive individuals, have higher VC both at rest (3.48 +/- 1.26 vs. 2.67 +/-
      0.72 units, p = 0.05) and peak reactive hyperemia (25, 02 +/- 8.18 vs. 18.66 +/-
      6.07 units, p = 0.04). The indices of cardiac autonomic modulation were similar
      between the groups. However, in the peripheral autonomic modulation, greater
      variability was observed in prehypertensive patients compared to normotensive
      individuals (9.4 [4.9-12.7] vs. 18.3 [14.8-26.7] mmHg2; p < 0.01) and higher
      spectral components of very low (6.9 [2.0-11.1] vs. 13.5 [10.7-22.4] mmHg2, p =
      0.01) and low frequencies (1.7 [1.0-3.0] vs. 3.0 [2.0-4.0] mmHg2, p = 0.04) of
      SBP. Additionally, we observed a lower gain of baroreflex control in
      prehypertensive patients compared to normotensive patients (12.16 +/- 4.18 vs.
      18.23 +/- 7.11 ms/mmHg, p = 0.03), but similar delay time (-1.55 +/- 0.66 vs. 
      1.58 +/- 0.72 s, p = 0.90). CONCLUSION: Prehypertensive patients with FHSAH have
      autonomic dysfunction and increased vascular conductance when compared to
      normotensive patients with the same risk factor.

PMID- 29466486
TI  - Sports Practices and Cardiovascular Risk in Teenagers.
AB  - BACKGROUND: Cardiovascular diseases are the leading cause of deaths in the world,
      and many events could be prevented by healthy life habits. OBJECTIVES: To compare
      the occurrence of cardiovascular risk factors in adolescents enrolled at public
      schools in the city of Rio de Janeiro, including a renowned school for sport
      practices. METHODS: Cross-sectional study, convenience sampling of 422 students
      enrolled at the Experimental Olympic Gymnasium (EOG) and at Figueiredo Pimentel
      School (FP). Using descriptive analyses, continuous variables were expressed as
      mean and standard deviation or median and interquartile ranges, and the Student's
      t-test or the chi-square test, respectively, was used for comparisons. The sports
      were classified according to the metabolic equivalent of task (MET) (below or
      above 5). RESULTS: We included 274 students enrolled at the EOG and 148 at FP.
      Mean age was similar between schools -12.5 +/- 1.6 years at FP and 12.6 +/- 0.9
      at the EOG; 65.5% of the students at FP and 43.8% of the students at the EOG were
      female (p < 0.01). Significant differences in the prevalence of hypertension (20%
      vs. 6.3%, p < 0.01) and borderline cholesterol levels (27.7% vs. 17.3%, p = 0.01)
      were found between FP and EOG students, respectively. CONCLUSION: High prevalence
      of hypertension, overweight/obesity and altered blood lipid profile was found in
      this group of adolescents. Regular sports training program combined with little
      influence of their eating habits outside school may contribute to a better
      metabolic profile and reduction in cardiovascular risk factors in students.
      Public health measures are also need.

PMID- 29466487
TI  - High-Intensity Interval Training in Heart Transplant Recipients: A Systematic
      Review with Meta-Analysis.
AB  - Heart transplantation (HTx) is considered an efficient and gold-standard
      procedure for patients with end-stage heart failure. After surgery, patients have
      lower aerobic power (VO2max) and compensatory hemodynamic responses. The aim of
      the present study was to assess through a systematic review with meta-analysis
      whether high-intensity interval training (HIIT) can provide benefits for those
      parameters. This is a systematic review with meta-analysis, which searched the
      databases and data portals PubMed, Web of Science, Scopus, Science Direct and
      Wiley until December 2016 (pairs). The following terms and descriptors were used:
      "heart recipient" OR "heart transplant recipient" OR "heart transplant" OR
      "cardiac transplant" OR "heart graft". Descriptors via DeCS and Mesh were: "heart
      transplantation'' OR "cardiac transplantation". The words used in combination
      (AND) were: "exercise training" OR "interval training" OR "high intensity
      interval training" OR "high intensity training" OR "anaerobic training" OR
      "intermittent training" OR "sprint training". The initial search identified 1064
      studies. Then, only those studies assessing the influence of HIIT on the post-HTx
      period were added, resulting in three studies analyzed. The significance level
      adopted was 0.05. Heart transplant recipients showed significant improvement in
      VO2peak, heart rate and peak blood pressure in 8 to 12 weeks of intervention.

PMID- 29466488
TI  - Uninterrupted Use of Oral Anticoagulants for the Ablation of Atrial Flutter: A
      Single Center Cohort of 154 Patients.
AB  - BACKGROUND: The uninterrupted use of oral anticoagulation (OAC) with vitamin K
      antagonists (VKAs) for electrophysiology procedures has been more and more
      recommended. The clinical practice in our service recommends the continuous use
      of these drugs for atrial flutter ablation. There is little evidence as to the
      uninterrupted use of non-vitamin K antagonist oral anticoagulants (NOACs) in this
      scenario. OBJECTIVE: To compare the rates of complications related with the
      uninterrupted use of different types of oral anticoagulants in patients referred
      to atrial flutter (AFL) ablation. METHODS: Historical, single-center cohort of
      ablation procedures by AFL conducted from November 2012 to April 2016. The
      primary outcome was the occurrence of hemorrhagic or embolic complication during
      the procedure. The secondary outcome was the occurrence of stroke or transient
      ischemic attack (TIA) in follow-up. The statistical significance level was 5%.
      RESULTS: There were 288 ablations per AFL; 154 were carried out with the
      uninterrupted use of OAC (57.8% with VKA and 42.2% with NOAC). Mean age was 57 +/
      13 years. The rate of hemorrhagic complication during the procedure was 3% in
      each group (p = NS). The rate of stroke/TIA was, respectively, of 56/1,000 people
      year in the VKA group against zero/1,000 people-year in the NOAC group (p =
      0.02). CONCLUSION: In our population there were no hemorrhagic complications
      regarding the procedure of OAC use uninterruptedly, including NOACs. There was
      higher occurrence of stroke/TIA in the follow-up of the group of patients
      undergoing VKAs; however, this difference may not only be a result of the type of
      OAC used.

PMID- 29466489
TI  - Moderate Continuous Aerobic Exercise Training Improves Cardiomyocyte
      Contractility in Beta1 Adrenergic Receptor Knockout Mice.
AB  - BACKGROUND: The lack of cardiac beta1-adrenergic receptors (beta1-AR) negatively
      affects the regulation of both cardiac inotropy and lusitropy, leading, in the
      long term, to heart failure (HF). Moderate-intensity aerobic exercise (MCAE) is
      recommended as an adjunctive therapy for patients with HF. OBJECTIVE: We tested
      the effects of MCAE on the contractile properties of left ventricular (LV)
      myocytes from beta1 adrenergic receptor knockout (beta1ARKO) mice. METHODS: Four-
      to five-month-old male wild type (WT) and beta1ARKO mice were divided into
      groups: WT control (WTc) and trained (WTt); and beta1ARKO control (beta1ARKOc)
      and trained (beta1ARKOt). Animals from trained groups were submitted to a MCAE
      regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8
      weeks. P <= 0.05 was considered significant in all comparisons. RESULTS: The
      beta1ARKO and exercised mice exhibited a higher (p < 0.05) running capacity than
      WT and sedentary ones, respectively. The beta1ARKO mice showed higher body (BW),
      heart (HW) and left ventricle (LVW) weights, as well as the HW/BW and LVW/BW than
      WT mice. However, the MCAE did not affect these parameters. Left ventricular
      myocytes from beta1ARKO mice showed increased (p < 0.05) amplitude and velocities
      of contraction and relaxation than those from WT. In addition, MCAE increased (p
      < 0.05) amplitude and velocities of contraction and relaxation in beta1ARKO mice.
      CONCLUSION: MCAE improves myocyte contractility in the left ventricle of
      beta1ARKO mice. This is evidence to support the therapeutic value of this type of
      exercise training in the treatment of heart diseases involving beta1-AR
      desensitization or reduction.

PMID- 29466490
TI  - Heart Transplantation for Peripartum Cardiomyopathy: A Single-Center Experience.
AB  - BACKGROUND: Peripartum cardiomyopathy is an idiopathic disorder defined by the
      occurrence of acute heart failure during late pregnancy or post-partum period in
      the absence of any other definable cause. Its clinical course is variable and
      severe cases might require heart transplantation. OBJECTIVE: To investigate long
      term outcomes after heart transplantation (HT) for peripartum cardiomyopathy
      (PPCM). METHODS: Out of a single-center series of 1938 HT, 14 HT were performed
      for PPCM. We evaluated clinical characteristics, transplant-related
      complications, and long-term outcomes, in comparison with 28 sex-matched
      controls. Primary endpoint was death from any cause; secondary endpoints were
      transplant-related complications (rejection, infection, cardiac allograft
      vasculopathy). A value of p < 0.05 was considered of statistical significance.
      RESULTS: PPCM patients and matched controls were comparable for most variables
      (all p values > 0.05), except for a higher use of inotropes at the time of HT in
      PPCM group (p = 0.03). During a median follow-up of 7.7 years, 16 patients died,
      3 (21.5%) in PPCM group and 13 (46.5%) in control group. Mortality was
      significantly lower in PPCM group (p = 0.03). No significant difference was found
      in terms of transplant-related complications (p > 0.05). CONCLUSIONS: Long-term
      outcomes following HT for PPCM are favorable. Heart transplantation is a valuable
      option for PPCM patients who did not recover significantly under medical
      treatment.

PMID- 29466491
TI  - The Presence and Extension of Myocardial Fibrosis in the Undetermined Form of
      Chagas' Disease: A Study Using Magnetic Resonance.
AB  - BACKGROUND: Previous data has shown that patients in the indeterminate form of
      Chagas disease may present myocardial fibrosis as shown on through magnetic
      resonance imaging (MRI). However, there is little information available regarding
      the degree of severity of myocardial fibrosis in these individuals. This variable
      has the potential to predict the evolution of Chagas' disease into its cardiac
      form. OBJECTIVES: To describe the frequency and extent of myocardial fibrosis
      evaluated using an MRI in patients in the indeterminate form, and to compare it
      with other forms of the disease. METHODS: Patients were admitted one after
      another. Their clinical history was collected and they were submitted to
      laboratory exams and an MRI. RESULTS: Sixty-one patients with Chagas' disease,
      with an average age of 58 +/- 9 years old, 17 patients in the indeterminate form,
      16 in the cardiac form without left ventricular (LV) dysfunction and 28 in the
      cardiac form with LV dysfunction were studied. P <0.05 was considered to be
      statistically significant. Late enhancement was detected in 37 patients (64%).
      Myocardial fibrosis was identified in 6 individuals in indeterminate form (41%;
      95% CI 23-66) in a proportion similar to that observed in cardiac form without LV
      dysfunction (44%); p = 1.0. Among the individuals with fibrosis, the total area
      of the affected myocardium was 4.1% (IIQ: 2.1 - 10.7) in the indeterminate form
      versus 2.3% (IIQ: 1-5) in the cardiac form without LV (p = 0.18). The left
      ventricular fraction ejection in subjects in the indeterminate form was similar
      to that of the individuals in the cardiac form without ventricular dysfunction (p
      = 0.09). CONCLUSION: The presence of fibrosis in the indeterminate form of
      Chagas' disease has a frequency and extension similar to that of in the cardiac
      form without dysfunction, suggesting that the former is part of a subclinical
      disease spectrum, rather than lacking cardiac involvement.

PMID- 29466492
TI  - Urbanization is Associated with Increased Trends in Cardiovascular Mortality
      Among Indigenous Populations: the PAI Study.
AB  - BACKGROUND: The cardiovascular risk burden among diverse indigenous populations
      is not totally known and may be influenced by lifestyle changes related to the
      urbanization process. OBJECTIVES: To investigate the cardiovascular (CV)
      mortality profile of indigenous populations during a rapid urbanization process
      largely influenced by governmental infrastructure interventions in Northeast
      Brazil. METHODS: We assessed the mortality of indigenous populations (>= 30 y/o)
      from 2007 to 2011 in Northeast Brazil (Bahia and Pernambuco states).
      Cardiovascular mortality was considered if the cause of death was in the ICD-10
      CV disease group or if registered as sudden death. The indigenous populations
      were then divided into two groups according to the degree of urbanization based
      on anthropological criteria:9,10 Group 1 - less urbanized tribes (Funi-o,
      Pankararu, Kiriri, and Pankarare); and Group 2 - more urbanized tribes (Tuxa,
      Truka, and Tumbalala). Mortality rates of highly urbanized cities (Petrolina and
      Juazeiro) in the proximity of indigenous areas were also evaluated. The analysis
      explored trends in the percentage of CV mortality for each studied population.
      Statistical significance was established for p value < 0.05. RESULTS: There were
      1,333 indigenous deaths in tribes of Bahia and Pernambuco (2007-2011): 281 in
      Group 1 (1.8% of the 2012 group population) and 73 in Group 2 (3.7% of the 2012
      group population), CV mortality of 24% and 37%, respectively (p = 0.02). In 2007
      2009, there were 133 deaths in Group 1 and 44 in Group 2, CV mortality of 23% and
      34%, respectively. In 2009-2010, there were 148 deaths in Group 1 and 29 in Group
      2, CV mortality of 25% and 41%, respectively. CONCLUSIONS: Urbanization appears
      to influence increases in CV mortality of indigenous peoples living in
      traditional tribes. Lifestyle and environmental changes due to urbanization added
      to suboptimal health care may increase CV risk in this population.

PMID- 29466493
TI  - Preventable adverse drug events in critically ill HIV patients: Is the detection
      of potential drug-drug interactions a useful tool?
AB  - OBJECTIVES: The aim of this study was to develop a strategy to identify adverse
      drug events associated with drug-drug interactions by analyzing the prescriptions
      of critically ill patients. METHODS: This retrospective study included HIV/AIDS
      patients who were admitted to an intensive care unit between November 2006 and
      September 2008. Data were collected in two stages. In the first stage, three
      prescriptions administered throughout the entire duration of these patients'
      hospitalization were reviewed, with the Micromedex database used to search for
      potential drug-drug interactions. In the second stage, a search for adverse drug
      events in all available medical, nursing and laboratory records was performed.
      The probability that a drug-drug interaction caused each adverse drug events was
      assessed using the Naranjo algorithm. RESULTS: A total of 186 drug prescriptions
      of 62 HIV/AIDS patients were analyzed. There were 331 potential drug-drug
      interactions, and 9% of these potential interactions resulted in adverse drug
      events in 16 patients; these adverse drug events included treatment failure
      (16.7%) and adverse reactions (83.3%). Most of the adverse drug reactions were
      classified as possible based on the Naranjo algorithm. CONCLUSIONS: The approach
      used in this study allowed for the detection of adverse drug events related to 9%
      of the potential drug-drug interactions that were identified; these adverse drug
      events affected 26% of the study population. With the monitoring of adverse drug
      events based on prescriptions, a combination of the evaluation of potential drug
      drug interactions by clinical pharmacy services and the monitoring of critically
      ill patients is an effective strategy that can be used as a complementary tool
      for safety assessments and the prevention of adverse drug events.

PMID- 29466494
TI  - Granulocyte Colony-Stimulating Factor Combined with Methylprednisolone Improves
      Functional Outcomes in Rats with Experimental Acute Spinal Cord Injury.
AB  - OBJECTIVES: To evaluate the effects of combined treatment with granulocyte colony
      stimulating factor (G-CSF) and methylprednisolone in rats subjected to
      experimental spinal cord injury. METHODS: Forty Wistar rats received a moderate
      spinal cord injury and were divided into four groups: control (no treatment); G
      CSF (G-CSF at the time of injury and daily over the next five days);
      methylprednisolone (methylprednisolone for 24 h); and G-CSF/Methylprednisolone
      (methylprednisolone for 24 h and G-CSF at the time of injury and daily over the
      next five days). Functional evaluation was performed using the Basso, Beattie and
      Bresnahan score on days 2, 7, 14, 21, 28, 35 and 42 following injury. Motor
      evoked potentials were evaluated. Histological examination of the spinal cord
      lesion was performed immediately after euthanasia on day 42. RESULTS: Eight
      animals were excluded (2 from each group) due to infection, a normal Basso,
      Beattie and Bresnahan score at their first evaluation, or autophagy, and 32 were
      evaluated. The combination of methylprednisolone and G-CSF promoted greater
      functional improvement than methylprednisolone or G-CSF alone (p<0.001). This
      combination also exhibited a synergistic effect, with improvements in hyperemia
      and cellular infiltration at the injury site (p<0.001). The groups displayed no
      neurophysiological differences (latency p=0.85; amplitude p=0.75). CONCLUSION:
      Methylprednisolone plus G-CSF promotes functional and histological improvements
      superior to those achieved by either of these drugs alone when treating spinal
      cord contusion injuries in rats. Combining the two drugs did have a synergistic
      effect.

PMID- 29466495
TI  - Monitoring auditory cortical plasticity in hearing aid users with long latency
      auditory evoked potentials: a longitudinal study.
AB  - OBJECTIVE: The objective of this study was to compare long-latency auditory
      evoked potentials before and after hearing aid fittings in children with
      sensorineural hearing loss compared with age-matched children with normal
      hearing. METHODS: Thirty-two subjects of both genders aged 7 to 12 years
      participated in this study and were divided into two groups as follows: 14
      children with normal hearing were assigned to the control group (mean age 9 years
      and 8 months), and 18 children with mild to moderate symmetrical bilateral
      sensorineural hearing loss were assigned to the study group (mean age 9 years and
      2 months). The children underwent tympanometry, pure tone and speech audiometry
      and long-latency auditory evoked potential testing with speech and tone burst
      stimuli. The groups were assessed at three time points. RESULTS: The study group
      had a lower percentage of positive responses, lower P1-N1 and P2-N2 amplitudes
      (speech and tone burst), and increased latencies for the P1 and P300 components
      following the tone burst stimuli. They also showed improvements in long-latency
      auditory evoked potentials (with regard to both the amplitude and presence of
      responses) after hearing aid use. CONCLUSIONS: Alterations in the central
      auditory pathways can be identified using P1-N1 and P2-N2 amplitude components,
      and the presence of these components increases after a short period of auditory
      stimulation (hearing aid use). These findings emphasize the importance of using
      these amplitude components to monitor the neuroplasticity of the central auditory
      nervous system in hearing aid users.

PMID- 29466503
TI  - Dioctophyme renale (Nematoda: Dioctophymatidae) in Leopardus geoffroyi
      (Carnivora: Felidae) in the Neotropical region.
AB  - Parasitic diseases affecting wild carnivores remain largely unknown or poorly
      described. Dioctophymosis is a parasitosis caused by the nematode Dioctophyme
      renale that is found worldwide. It affects domestic and wild animals and has been
      reported frequently in Brazil. This paper reports dioctophymosis in a wild felid
      for the first time.

PMID- 29466509
TI  - Translation and cross-cultural adaptation of the Detailed Assessment of Speed of
      Handwriting 17+ to Brazilian Portuguese: conceptual, item and semantic
      equivalence.
AB  - PURPOSE: Perform a cross-cultural adaptation of the Detailed Assessment of Speed
      of Handwriting 17+ (DASH 17+) for Brazilians. METHODS: Evaluation of (1)
      conceptual, item and (2) semantic equivalence, with assistance of four
      translators and application of a pilot study to 36 students. RESULTS: (1) The
      concepts and items are equivalent in the British and Brazilian cultures. (2)
      Adaptations were made concerning the English language pangram used in copying
      tasks and selection of the lower-case, cursive handwriting in the alphabet
      writing task. Application of the pilot study verified acceptability and
      understanding of the proposed tasks by the students. CONCLUSION: The Brazilian
      Portuguese version of the DASH 17+ was presented after finalization of the
      conceptual, item and semantic equivalence of the instrument. Further studies on
      psychometric properties should be conducted with the purpose of measuring the
      speed of handwriting in youngsters and adults with greater reliability and
      validity to the procedure.

PMID- 29466510
TI  - Educational intervention assessment aiming the hearing preservation of workers at
      a hospital laundry.
AB  - OBJECTIVE: Evaluate the effectiveness of educational interventions on hearing
      health developed at a hospital laundry. METHODS: Quantitative assessment
      conducted at a hospital laundry. The study sample comprised 80 workers of both
      genders divided into two groups: Study Group (SG) and Control Group (CG). The
      educational interventions in hearing preservation were evaluated based on a
      theoretical approach using the Participatory Problem-based Methodology in five
      workshops. To assess the results of the workshops, an instrument containing 36
      questions on knowledge, attitudes, and practices in hearing preservation at work
      was used. Questionnaires A and B were applied prior to and one month after
      intervention, respectively. The answers to both questionnaires were analyzed by
      group according to gender and schooling. RESULTS: Results of the pre-intervention
      phase showed low scores regarding knowledge about hearing health in the work
      setting for both groups, but significant improvement in knowledge was observed
      after intervention in the SG, with 77.7% of the answers presenting significant
      difference between the groups. There was also an improvement in the mean scores,
      with 35 responses (95.22%) presenting scores >4 (considered adequate). The women
      presented lower knowledge scores than the men; however, these differences were
      not observed in the SG after the workshops. Schooling was not a relevant factor
      in the assessment. CONCLUSION: The educational proposal grounded in the
      Participatory Problem-based Methodology expanded knowledge about hearing health
      at work among the participants.

PMID- 29466511
TI  - Comparison between different methods of breast implant volume choice and degree
      of postoperative satisfaction.
AB  - OBJECTIVES: to assess the degree of patient satisfaction after undergoing breast
      augmentation and compare three different, easy, inexpensive and universal methods
      of preoperative choice of breast implant volume. METHODS: a prospective study was
      carried out at University Hospital Pedro Ernesto of State University of Rio de
      Janeiro, in 94 women from Rio de Janeiro, aged 18 to 49 years, submitted to
      breast augmentation mammaplasty with breast implant due to hypomastia. All
      implants were textured, with a round base and high projection and were introduced
      into the retroglandular space through an inframammary access. The patients were
      divided into three groups: Control, Silicone and MamaSize(r), with 44, 25 and 25
      patients, respectively. Satisfaction questionnaires were applied in the pre and
      postoperative periods by the same evaluator, through the visual analogue scale,
      in which '0' meant very unsatisfied and '100' very satisfied for the four
      variables: shape, size, symmetry and consistency. The degree of satisfaction with
      the surgical scar was also assessed in the postoperative period. RESULTS: when
      the preoperative and postoperative satisfaction levels were compared, there was a
      difference in all variables for the three groups, with statistical significance.
      However, when the postoperative data were compared with each other, there was no
      significant difference. The degree of satisfaction with the surgical scar was
      high. CONCLUSION: the augmentation mammaplasty with breast implant had a high
      index of satisfaction among patients. However, there was no difference in the
      degree of satisfaction in the postoperative period between the three
      methodologies of breast volume measurement.

PMID- 29466512
TI  - The role of computerized tomography in penetrating abdominal trauma.
AB  - OBJECTIVE: to evaluate the role of abdominal computed tomography in the
      management of penetrating abdominal trauma. METHODS: we conducted a historical
      cohort study of patients treated for penetrating trauma in the anterior abdomen,
      dorsum or thoracoabdominal transition, that were submitted to a computed
      tomography carried out on admission. We evaluated the location of the wound and
      the presence of tomographic findings, and the management of these patients as for
      nonoperative treatment or laparotomy. We calculated the sensitivity and
      specificity of computed tomography according to the evolution of the nonoperative
      treatment or the surgical findings. RESULTS: we selected 61 patients, 31 with
      trauma to the anterior abdomen and 30 to the dorsum or thoracoabdominal
      transition. The mortality rate was 6.5% (n=4), all in the late postoperative
      period. Eleven patients with trauma to the anterior abdomen were submitted to
      nonoperative treatment, and 20, to laparotomy. Of the 30 patients with trauma to
      the dorsum or thoracoabdominal transition, 23 underwent nonoperative treatment
      and seven, laparotomy. There were three nonoperative treatment failures. In
      penetrating trauma of the anterior abdomen, the sensitivity of computed
      tomography was 94.1% and the negative predictive value was 93.3%. In dorsal or
      thoracoabdominal transition lesions, the sensitivity was 90% and the negative
      predictive value was 95.5%. In both groups, the specificity and the positive
      predictive value were 100%. CONCLUSION: the accuracy of computed tomography was
      adequate to guide the management of stable patients who could be treated
      conservatively, avoiding mandatory surgery in 34 patients and reducing the
      morbidity and mortality of non-therapeutic laparotomies.

PMID- 29466513
TI  - The experience of an Academic League: the positive impact on knowledge about
      trauma and emergency.
AB  - OBJECTIVE: to evaluate the knowledge growth of the members of the Trauma,
      Resuscitation and Emergency League in comparison with a nonparticipating group,
      with similar characteristics, at the Fluminense Federal University. METHODS: we
      evaluated 50 league members and 50 non-members (control group) through
      questionnaires applied at the beginning and end of a school year. We used a
      generalized linear model, with interaction effect between groups and tests
      (multiple comparisons with Bonferroni correction). We included the following
      control variables: gender, period, age, and attendance to some other course on a
      similar topic. RESULTS: there was an increase of 22 percentage points (p<0.001)
      for the group with more than 75% presence in the League compared with the eight
      points in the control group (p<0.05). There was no statistically significant
      growth for the group with less than 75% presence. CONCLUSION: the growth of
      knowledge was significantly higher in the group that assiduously participated in
      the League, which reinforces its importance in complementing the traditional
      content of medical courses.

PMID- 29466514
TI  - Basic ultrasound training assessment in the initial abdominal trauma screening.
AB  - OBJECTIVE: to verify the efficiency and usefulness of basic ultrasound training
      in trauma (FAST - Focused Assessment with Sonography in Trauma) for emergency
      physicians in the primary evaluation of abdominal trauma. METHODS: a longitudinal
      and observational study was carried out from 2015 to 2017, with 11 emergency
      physicians from Hospital Universitario do Oeste do Parana, submitted to
      ultrasound training in emergency and trauma (USET(r) - SBAIT). FAST results
      started to be collected two months after the course. These were compared with a
      composite score of complementary exams and surgical findings. Information was
      stored in a Microsoft Excel program database and submitted to statistical
      analysis. RESULTS: FAST was performed in 120 patients. In the study, 38.4% of the
      assessed patients had a shock index >=0.9. The composite score detected 40
      patients with free peritoneal fluid, whereas FAST detected 27 cases. The method
      sensitivity was 67.5%, specificity was 98.7%, the positive predictive value was
      96.4%, the negative predictive value was 85.39% and accuracy was 88%. All those
      with a positive FAST had a shock index >=0.9. Fifteen patients with positive FAST
      and signs of instability were immediately submitted to surgery. CONCLUSIONS: the
      basic training of emergency physicians in FAST showed efficiency and usefulness
      in abdominal trauma assessment. Due to its low cost and easy implementation, this
      modality should be considered as a screening strategy for patients with abdominal
      trauma in health systems.

PMID- 29466515
TI  - Individual deprivation, regional deprivation, and risk for oral clefts in
      Argentina.
AB  - OBJECTIVE: The aim of this study was to analyze the effects of individual low
      socioeconomic status (SES) and deprived geographical area (GA) on the occurrence
      of isolated cleft lip with or without cleft palate (CL+/-P) in Argentina.
      METHODS: This case-control study included 577 newborns with isolated CL+/-P and
      13 344 healthy controls, born between 1992 and 2001, from a total population of
      546 129 births in 39 hospitals in Argentina. Census data on unsatisfied basic
      needs were used to establish the degree of geographical area deprivation. An SES
      index for each individual was established, using maternal age, gravidity, low
      paternal and maternal education, and low-level paternal occupation. Logistic
      regression was used to assess the effects of low SES and of deprived GA on CL+/
      P. RESULTS: A slightly increased risk of CL+/-P was observed in mothers with a
      low SES, while a deprived GA showed no effect. Native ancestry, acute maternal
      illnesses, and poor prenatal care were significant risk factors for CL+/-P for
      the mothers with low SES, after using propensity scores to adjust for the
      demographic characteristics in cases and controls. CONCLUSIONS: Low individual
      SES slightly increased the risk for CL+/-P, but a deprived GA did not have that
      effect. There was no interaction between individual SES and deprived GA. Factors
      related to low individual SES-including poor prenatal care, low parental
      education, lack of information, and lifestyle factors-should be primarily
      targeted as risk factors for CL+/-P rather than factors related to a deprived
      place of residence.

PMID- 29466516
TI  - [Infoxication in health. Health information overload on the Internet and the risk
      of important information becoming invisible].
AB  - OBJECTIVE: The objectives of this study were to: 1) raise awareness of the volume
      of quality health information on the Internet; 2) explore perceptions of
      information professionals with regard to the use of qualified sources for health
      decision-making; and 3) make recommendations that facilitate strengthening health
      worker capacities and institutional competencies related to digital literacy.
      METHODS: A non-experimental, descriptive cross-sectional study was conducted with
      a non-probability sample of 32 information professionals from nine countries.
      Internet information was compiled on the volume of content in Internet tools,
      social networks, and health information sources. Searches in English and Spanish
      were carried out using the keywords Ebola, Zika, dengue, chikungunya, safe food,
      health equity, safe sex, and obesity. Finally, information was obtained on
      opportunities for formal education on the subjects of digital literacy,
      information management, and other related topics. RESULTS: Selecting only four
      diseases with a high impact on public health in May 2016 and averaging minimum
      review time for each information product, it would take more than 50 years
      without sleeping to consult everything that is published online about dengue,
      Zika, Ebola, and chikungunya. CONCLUSION: We conclude that public health would
      benefit from: health institutions implementing formal knowledge management
      strategies; academic health sciences institutions incorporating formal digital
      literacy programs; and having health workers who are professionally responsible
      and functional in the information society.

PMID- 29466517
TI  - Potential occurrence of Zika from subtropical to temperate Argentina considering
      the basic reproduction number (R0).
AB  - OBJECTIVE: To assess the potential occurrence of Zika transmission throughout
      Argentina by the mosquito Aedes aegypti considering the basic reproduction number
      (R0). METHODS: A model originally developed for dengue was adapted for Zika. R0
      was estimated as a function of seven parameters, three of them were considered
      temperature-dependent. Seasonal Zika occurrence was evaluated in 9 locations
      representing different climatic suitability for the vector. Data of diary
      temperatures were extracted and included in the model. A threshold of R0 = 1 was
      fixed for Zika occurrence. Sensitivity analyses were performed to evaluate the
      uncertainty around the results. RESULTS: Zika transmission has the potential to
      occur in all studied locations at least in some moment of the year. In the
      northern region, transmission might be possible throughout the whole year or with
      an interruption in winter. The maximum R0 was estimated in 6.9, which means an
      average of 7 secondary cases from a primary case. The probabilistic sensitivity
      analysis showed that during winter the transmission can only be excluded in the
      southern fringe of geographic distribution of the vector and in part of central
      Argentina. CONCLUSION: Zika virus has the potential to be transmitted in
      Argentina throughout the current geographic range of the mosquito vector.
      Although the transmission would be mainly seasonal, the possibility of winter
      transmission cannot be excluded in northern and central Argentina, meaning that
      there is a potential endemic maintenance of the disease.

PMID- 29466518
TI  - Response regarding Colombian regulation of biotherapeutic products.

PMID- 29466519
TI  - A road map for leptospirosis research and health policies based on country needs
      in Latin America.
AB  - This report summarizes the presentations, discussions and the recommendations
      coming from the Oswaldo Cruz Institute/FIOCRUZ International Workshop for
      Leptospirosis Research Based on Country Needs and the 5th Global Leptospirosis
      Environmental Action Network meeting, which was held in the city of Rio de
      Janeiro, Brazil, 10-12 November 2015. The event focused on health policy and
      worked to develop a road map as a consensus document to help guide decision
      making by policymakers, funding bodies, and health care professionals. The
      direction that leptospirosis research should take in the coming years was
      emphasized, taking into account the needs of countries of Latin America, as well
      as experiences from other world regions, as provided by international experts.
      The operational concepts of "One Health" and translational research underlaid the
      discussions and the resulting recommendations. Despite the wide geographic
      distribution of leptospirosis and its impact in terms of incidence, morbidity,
      and mortality, leptospirosis is not yet considered a "tool-ready" disease for
      global initiatives. Surveillance programs need new tools and strategies for early
      detection, prevention, and follow-up. The major recommendations developed at the
      Rio meeting cover both health policy and research. The health policy
      recommendations should be taken into account by decisionmakers, government
      officials, and the Pan American Health Organization. The priorities for research,
      technological development, and innovation should be considered by research
      institutions, universities, and stakeholders.

PMID- 29466520
TI  - ?

PMID- 29466521
TI  - Prolonged Zika virus viremia in a patient with Guillain-Barre syndrome in
      Trinidad and Tobago.
AB  - An emerging mosquito-borne flavivirus, Zika virus (ZIKV) is a significant public
      health concern because of the syndromes associated with the infection. In
      addition, ZIKV is considered a major problem due to large-scale spread of the
      disease and the possible clinical complications for the central nervous system,
      especially Guillain-Barre syndrome (GBS) and microcephaly. Since the introduction
      of ZIKV in the Caribbean, molecular detection of the viral RNA has been utilized
      as a more specific and sensitive approach to demonstrating acute infection.
      However, it is generally accepted that the virus has a short viremic period,
      generally less than 5 days. Serologic testing has the inconvenience of strong
      cross-reactivity among flaviviruses, such as dengue and yellow fever. As part of
      the laboratory surveillance activities for Zika and other arboviruses at the
      Caribbean Public Health Agency, in 2016 a sample from a male who was clinically
      diagnosed with GBS tested positive for Zika virus by real-time polymerase chain
      reaction (rRT-PCR). The serum sample had been taken on day 21 after the onset of
      symptoms. The case had initially been characterized as a typical ZIKV infection
      (mild fever with a generalized maculopapular rash). Later, weakness of limbs and
      other peripheral neurological symptoms appeared. Enzyme-linked immunoassay
      (ELISA) showed that the sample was negative for IgM antibodies against Zika,
      Chikungunya, and dengue viruses. The plaque reduction neutralization test was
      positive for ZIKV. This indicated parallel development of viremia and immune
      response against ZIKV. Recent reports have demonstrated a longer duration of the
      viremia in ZIKV infections. However, our report is the first one that links the
      infection with extended viremia and the development in parallel of a GBS case.

PMID- 29466522
TI  - [Health technology assessment for decision-making in Latin America: good practice
      principles].
AB  - OBJECTIVE: Identify the most relevant, applicable, and priority good practice
      principles in health technology assessment (HTA) in Latin America, and potential
      barriers to implementing them in the region. METHODS: HTA good practice
      principles postulated worldwide were identified and then explored through a
      deliberative process in a forum of evaluators, funders, and technology producers.
      RESULTS: Forty-two representatives from ten Latin American countries participated
      in the forum. The good practice principles postulated at the international level
      were considered valid and potentially applicable in Latin America. Five
      principles were identified as priorities and as having greater potential to be
      expanded at this time: transparency in carrying out HTA; involvement of
      stakeholders in the HTA process; existence of mechanisms to appeal decisions;
      existence of clear mechanisms for HTA priority-setting; and existence of a clear
      link between assessment and decision-making. The main challenge identified was to
      find a balance between application of these principles and available resources,
      to prevent the planned improvements from jeopardizing report production times and
      failing to meet decision-makers' needs. CONCLUSIONS: The main recommendation was
      to gradually advance in improving HTA and its link to decision-making by
      developing appropriate processes for each country, without attempting to impose,
      in the short term, standards taken from examples at the international level
      without adequate adaptation to the local context.

PMID- 29466523
TI  - [Breastfeeding and externalizing behaviors in childhood and adolescence in a
      birth cohort].
AB  - OBJECTIVE: To assess the association between breastfeeding duration and
      externalizing behaviors in childhood and adolescence. METHODS: Data from the 1993
      Pelotas Birth Cohort was used. Information on breastfeeding was assessed at 12
      months of age. Behavior was assessed at 4 years of age using the Child Behavior
      Checklist (CBCL), and at ages 11 and 15 years using the Strengths and
      Difficulties Questionnaire (SDQ), both administered to the mother or caretaker.
      Of 5 249 cohort participants, those with complete data on breastfeeding and
      externalizing behaviors were included: 630 children at 4 years of age, 1 277
      adolescents at 11 years, and 1 199 at 15 years. Poisson regression with robust
      variance was used to assess the association between breastfeeding duration and
      externalizing behaviors. RESULTS: After adjustment for confounders, children who
      were breastfed for least 6 months had lower risk of hyperactivity (RR = 0.54;
      95%CI: 0.32-0.91) at age 11 compared to those breastfed for less than 1 month.
      However, no association was observed between breastfeeding duration and
      externalizing behaviors at ages 4 and 15. CONCLUSIONS: Although breastfeeding for
      at least 6 months was inversely associated with hyperactivity at 11 years of age
      no association was observed at 4 and 15 years of age. Further longitudinal
      studies should focus on other aspects influencing externalizing behaviors, such
      as presence of the father in the family, domestic violence and abuse, and the
      quality of mother-child relationship.

PMID- 29466524
TI  - [Social determinants of intestinal parasitism, malnutrition, and anemia:
      systematic review].
AB  - OBJECTIVE: Characterize the publications on social determinants of intestinal
      parasitism, malnutrition, and anemia at the global level. METHODS: A systematic
      review was conducted of the scientific literature in Pubmed, Science Direct,
      SciELO, LILACS, and Google Scholar with eight search strategies, guaranteeing
      completeness and replicability, following the phases of the PRISMA guidelines.
      RESULTS: The review included 18 studies on malnutrition, three on parasitism,
      three on anemia, and two on both parasitism and malnutrition; 65.4% of the
      studies were from South America and 69.2% were carried out among children. The
      prevalence of intestinal parasitism ranged between 30.6% and 83.3%; anemia, 19.7%
      to 48.0%; and malnutrition, 0.0% to 67.8%. It was found that biological and
      psychosocial determinants were most frequently studied; the most frequently
      studied intermediate determinants were related to housing and income; and
      structural determinants were least investigated. The social determinants common
      to the three conditions include: living in homes with poor sanitary conditions,
      rural areas, inadequate housing, inadequate water supply, access barriers to the
      medical system, young parents with little schooling, precarious employment, and
      low income. CONCLUSION: The majority of publications do not conduct a multilevel
      analysis for individual, intermediate, or structural determinants. Greater
      efforts are needed in health policies that address the social determinants of
      inequality with respect to parasitism, malnutrition, and anemia, mainly in
      categories as macroeconomic policy, social class, labor market, culture, values,
      and territory.

PMID- 29466525
TI  - [Chronic diseases in the population affected by the armed conflict in Colombia,
      2015].
AB  - OBJECTIVE: The purpose of this study was to identify the most frequent non-mental
      chronic illnesses in the Colombian population affected by the armed conflict.
      METHODOLOGY: A cross-sectional study using data from the National Mental Health
      Survey 2015. The study population was stratified by sex and age and other general
      data were extracted, including education and poverty level, measured by the
      Multidimensional Poverty Index. Data analysis was based on information from
      people who reported having been victims of the Colombian armed conflict at some
      time in their lives; the frequency of presentation of non-mental chronic
      illnesses was reported as a measure of indirect relative risk. RESULTS:
      Information on 10,764 people over 18 years of age was described, this being a
      representative sample at the national level. It was found that 10.4% of subjects
      affected by the armed conflict have a high educational level (technical school or
      university), and that 43.6% are living in conditions of poverty or vulnerability.
      The non-mental chronic illnesses identified were: hypertension 20.4% (CI95%: 15.7
      26.1); diabetes 6.7% (CI95%: 4.4-10.3); rheumatologic diseases 10.4% (CI95%: 7.1
      14.9); gastrointestinal diseases 19.1% (CI95%: 14.5-24.7); and chronic pain 6.9%
      (CI95%: 4.2-11). CONCLUSIONS: The population affected by the armed conflict is
      apparently at greater risk of presenting non-mental chronic illnesses such as
      hypertension and diabetes, which shows the vulnerability of these communities.

PMID- 29466526
TI  - [Spatial distribution of hospital discharges of cases of viral infection from
      mosquito bites in Mexico in the period 2004-2014].
AB  - OBJECTIVE: Determine the spatial distribution of hospital discharges of viral
      fever caused by mosquito bites in Mexico and characterize its historical trend in
      the period 2004-2014. METHODS: An exploratory cross-sectional inferential
      analysis was performed. The primary data were obtained from the hospital
      discharge registries of the National Health Information System (SINAIS) for the
      period 2004-2014. In order to identify clusters of reported cases, indicators of
      geographical association were estimated and risk areas established on the basis
      of environmental determinants validated with estimated relative concentration
      measurements. In order to determine the temporal trend and age structure of the
      cases, growth rates were estimated and density curves constructed. RESULTS: The
      geographic distribution of these hospital discharges in Mexico follows a
      focalized pattern. In total, a high concentration was detected in clusters made
      up of 20 municipalities, 9 of which were located in the state of Sinaloa. In 37%
      of states in the country, the concentrations of hospital discharges of viral
      fever cases were higher than those for the country as a whole, and their
      localization indices ranged from 5.79 in Sinaloa to 1.17 in Campeche. CONCLUSION:
      Geographic information, information on the link found between areas at high risk
      for transmission of infection due to the presence of the transmitting vector, and
      information on social conditions such as poverty are useful for designing
      strategies for the prevention and control of emerging arthropod-borne viral
      infections, such as the Zika virus, in Mexico.

PMID- 29466527
TI  - How Colombia's biosimilar regulation departs from international norms.

PMID- 29466528
TI  - [Future type 2 diabetes mellitus scenario estimated with a predictive dynamic
      simulation model].
AB  - OBJECTIVE: Develop a predictive dynamic model to estimate future scenarios for
      the incidence rate of type 2 diabetes mellitus (T2DM). METHODS: A retrospective
      ecological study was conducted in 2013-2015 in the city of San Luis Potosi,
      Mexico. Secondary official data from the 58 municipalities making up the state of
      San Luis Potosi were analyzed. Linear correlation, multiple linear regression,
      and structural equations were carried out, and four predictive dynamic submodels
      were developed: T2DM, urban population, inhabited private dwellings that have
      television, and population aged 45-49 years. A holistic model was also developed.
      RESULTS: The structural model explains 27.2% of total variance in type 2 diabetes
      mellitus. Percentage of inhabited dwellings that have television weighs 4.46 non
      standard units on diabetes; that of urban population, 2.84; and that of
      population aged 45-49 years, 156.69. Estimated scenarios for T2DM per 100 000
      population for the years 2015, 2020, 2025, and 2030 were 1,052.4, 1,413.7,
      1,850.1, and 2,351.1 respectively. CONCLUSION: The T2DM scenario shows
      exponential growth from 2000 to 2030. Risk factors according to the weight they
      represent in occurrence of the disease were: population aged 45-49 years,
      inhabited private dwellings that have television, and urban population.

PMID- 29466529
TI  - ?

PMID- 29466530
TI  - Cardiac Abnormalities in Patients With Hutchinson-Gilford Progeria Syndrome.
AB  - Importance: Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare disorder
      associated with premature death due to cardiovascular events during the second
      decade of life. However, because of its rarity (107 identified living patients),
      the natural history of cardiac disease remains uncharacterized. Therefore,
      meaningful cardiac end points for clinical trials have been difficult to
      establish. Objective: To examine the course of appearance of cardiac
      abnormalities in patients with HGPS to identify meaningful cardiac end points for
      use in future clinical trials. Design, Setting, and Participants: In this
      prospective, cross-sectional, observational study, 27 consecutive patients with
      clinically and genetically confirmed classic HGPS were evaluated at a single
      center for 1 visit from July 1, 2014, through February 29, 2016, before
      initiation of treatment. Exposure: Classic HGPS. Main Outcomes and Measures:
      Echocardiography was used to assess ventricular and valve function using standard
      techniques. Diastolic left ventricular (LV) function was assessed using tissue
      Doppler imaging. Previously published normative data were used to adjust findings
      to age and body size. Results: This study included 27 patients (median age, 5.6
      years; age range, 2-17 years; 15 [56%] male). Among echocardiographic indicators,
      LV diastolic dysfunction, defined as a tissue Doppler septal or lateral early
      velocity z score less than -2, was the most prevalent abnormality, seen in 16
      patients (59%). Diastolic dysfunction was seen in all age groups, and its
      prevalence increased with age, mirroring findings seen during normal aging.
      Indicators of LV diastolic function were more abnormal in older patients. The z
      scores for lateral and septal early velocities were lower (r = -0.77, P < .001;
      and r = -0.66, P < .001, respectively), whereas those for the ratio of early
      mitral inflow velocity to early diastolic tissue Doppler myocardial velocity were
      higher (r = 0.80, P < .001; and r = 0.72, P < .001, respectively) in older
      patients. Other echocardiographic findings, including LV hypertrophy, LV systolic
      dysfunction, and valve disease, were less prevalent in the first decade and were
      seen more frequently in the second decade. Conclusions and Relevance: In this
      largest-to-date cohort of patients with HGPS, LV diastolic dysfunction was the
      most prevalent echocardiographic abnormality and its prevalence increased with
      aging. Echocardiographic indicators of LV diastolic function may be useful end
      points in future clinical trials in this patient population.

PMID- 29466531
TI  - Association of Increased Chronicity of Depression With HIV Appointment
      Attendance, Treatment Failure, and Mortality Among HIV-Infected Adults in the
      United States.
AB  - Importance: Depression commonly affects adults with HIV and complicates the
      management of HIV. Depression among individuals with HIV tends to be chronic and
      cyclical, but the association of this chronicity with HIV outcomes (and the
      related potential for screening and intervention to shorten depressive episodes)
      has received little attention. Objective: To examine the association between
      increased chronicity of depression and multiple HIV care continuum indicators
      (HIV appointment attendance, treatment failure, and mortality). Design, Setting,
      and Participants: The study comprised an observational clinical cohort of 5927
      patients with 2 or more assessments of depressive severity who were receiving HIV
      primary care at 6 geographically dispersed US academic medical centers from
      September 22, 2005, to August 6, 2015. Main Outcomes and Measures: Missing a
      scheduled HIV primary care visit, detectable HIV RNA viral load (>=75 copies/mL),
      and all-cause mortality. Consecutive depressive severity measures were converted
      into a time-updated measure: percentage of days with depression (PDD), following
      established methods for determining depression-free days. Results: During 10 767
      person-years of follow-up, the 5927 participants (5000 men, 926 women, and 1
      intersex individual; median age, 44 years [range, 35-50 years]) had a median PDD
      of 14% (interquartile range, 0%-48%). During follow-up, 10 361 of 55 040
      scheduled visits (18.8%) were missed, 6191 of 28 455 viral loads (21.8%) were
      detectable, and the mortality rate was 1.5 deaths per 100 person-years.
      Percentage of days with depression showed a dose-response relationship with each
      outcome. Each 25% increase in PDD led to an 8% increase in the risk of missing a
      scheduled appointment (risk ratio, 1.08; 95% CI, 1.05-1.11), a 5% increase in the
      risk of a detectable viral load (risk ratio, 1.05; 95% CI, 1.01-1.09), and a 19%
      increase in the mortality hazard (hazard ratio, 1.19; 95% CI, 1.05-1.36). These
      estimates imply that, compared with patients who spent no follow-up time with
      depression (PDD, 0%), those who spent the entire follow-up time with depression
      (PDD, 100%) faced a 37% increased risk of missing appointments (risk ratio, 1.37;
      95% CI, 1.22-1.53), a 23% increased risk of a detectable viral load (risk ratio,
      1.23; 95% CI, 1.06-1.43), and a doubled mortality rate (hazard ratio, 2.02; 95%
      CI, 1.20-3.42). Conclusions and Relevance: Greater chronicity of depression
      increased the likelihood of failure at multiple points along the HIV care
      continuum. Even modest increases in the proportion of time spent with depression
      led to clinically meaningful increases in negative outcomes. Clinic-level trials
      of protocols to promptly identify and appropriately treat depression among adults
      living with HIV should be conducted to understand the effect of such protocols on
      shortening the course and preventing the recurrence of depressive illness and
      improving clinical outcomes.

PMID- 29466532
TI  - Association of Hippocampal Atrophy With Duration of Untreated Psychosis and
      Molecular Biomarkers During Initial Antipsychotic Treatment of First-Episode
      Psychosis.
AB  - Importance: Duration of untreated psychosis (DUP) has been associated with poor
      outcomes in schizophrenia, but the mechanism responsible for this association is
      not known. Objectives: To determine whether hippocampal volume loss occurs during
      the initial 8 weeks of antipsychotic treatment and whether it is associated with
      DUP, and to examine molecular biomarkers in association with hippocampal volume
      loss and DUP. Design, Setting, and Participants: A naturalistic longitudinal
      study with matched healthy controls was conducted at Shanghai Mental Health
      Center. Between March 5, 2013, and October 8, 2014, 71 medication-naive
      individuals with nonaffective first-episode psychosis (FEP) and 73 age- and sex
      matched healthy controls were recruited. After approximately 8 weeks, 31
      participants with FEP and 32 controls were reassessed. Exposures: The
      participants with FEP were treated according to standard clinical practice with
      second-generation antipsychotics. Main Outcomes and Measures: Hippocampal
      volumetric integrity (HVI) (an automated estimate of the parenchymal fraction in
      a standardized hippocampal volume of interest), DUP, 13 peripheral molecular
      biomarkers, and 14 single-nucleotide polymorphisms from 12 candidate genes were
      determined. Results: The full sample consisted of 71 individuals with FEP (39
      women and 32 men; mean [SD] age, 25.2 [7.7] years) and 73 healthy controls (40
      women and 33 men; mean [SD] age, 23.9 [6.4] years). Baseline median left HVI was
      lower in the FEP group (n = 57) compared with the controls (n = 54) (0.9275 vs
      0.9512; difference in point estimate, -0.020 [95% CI, -0.029 to -0.010]; P =
      .001). During approximately 8 weeks of antipsychotic treatment, left HVI
      decreased in 24 participants with FEP at a median annualized rate of -.03791 (
      4.1% annualized change from baseline) compared with an increase of 0.00115 (0.13%
      annualized change from baseline) in 31 controls (difference in point estimate, 
      0.0424 [95% CI, -0.0707 to -0.0164]; P = .001). The change in left HVI was
      inversely associated with DUP (r = -0.61; P = .002). Similar results were found
      for right HVI, although the association between change in right HVI and DUP did
      not achieve statistical significance (r = -0.35; P = .10). Exploratory analyses
      restricted to the left HVI revealed an association between left HVI and markers
      of inflammation, oxidative stress, brain-derived neurotrophic factor, glial
      injury, and markers reflecting dopaminergic and glutamatergic transmission.
      Conclusions and Relevance: An association between longer DUP and accelerated
      hippocampal atrophy during initial treatment suggests that psychosis may have
      persistent, possibly deleterious, effects on brain structure. Additional studies
      are needed to replicate these exploratory findings of molecular mechanisms by
      which untreated psychosis may affect hippocampal volume and to determine whether
      these effects account for the known association between longer DUP and poor
      outcome.

PMID- 29466534
TI  - Cultural Sensitivity in Deployed US Medical Personnel-Reply.

PMID- 29466533
TI  - Effectiveness of the DECIDE Interventions on Shared Decision Making and Perceived
      Quality of Care in Behavioral Health With Multicultural Patients: A Randomized
      Clinical Trial.
AB  - Importance: Few randomized clinical trials have been conducted with ethnic/racial
      minorities to improve shared decision making (SDM) and quality of care.
      Objective: To test the effectiveness of patient and clinician interventions to
      improve SDM and quality of care among an ethnically/racially diverse sample.
      Design, Setting, and Participants: This cross-level 2 * 2 randomized clinical
      trial included clinicians at level 2 and patients (nested within clinicians) at
      level 1 from 13 Massachusetts behavioral health clinics. Clinicians and patients
      were randomly selected at each site in a 1:1 ratio for each 2-person block.
      Clinicians were recruited starting September 1, 2013; patients, starting November
      3, 2013. Final data were collected on September 30, 2016. Data were analyzed
      based on intention to treat. Interventions: The clinician intervention consisted
      of a workshop and as many as 6 coaching telephone calls to promote communication
      and therapeutic alliance to improve SDM. The 3-session patient intervention
      sought to improve SDM and quality of care. Main Outcomes and Measures: The SDM
      was assessed by a blinded coder based on clinical recordings, patient perception
      of SDM and quality of care, and clinician perception of SDM. Results: Of 312
      randomized patients, 212 (67.9%) were female and 100 (32.1%) were male; mean (SD)
      age was 44.0 (15.0) years. Of 74 randomized clinicians, 56 (75.7%) were female
      and 18 (4.3%) were male; mean (SD) age was 39.8 (12.5) years. Patient-clinician
      pairs were assigned to 1 of the following 4 design arms: patient and clinician in
      the control condition (n = 72), patient in intervention and clinician in the
      control condition (n = 68), patient in the control condition and clinician in
      intervention (n = 83), or patient and clinician in intervention (n = 89). All
      pairs underwent analysis. The clinician intervention significantly increased SDM
      as rated by blinded coders using the 12-item Observing Patient Involvement in
      Shared Decision Making instrument (b = 4.52; SE = 2.17; P = .04; Cohen d = 0.29)
      but not as assessed by clinician or patient. More clinician coaching sessions
      (dosage) were significantly associated with increased SDM as rated by blinded
      coders (b = 12.01; SE = 3.72; P = .001; Cohen d = 0.78). The patient intervention
      significantly increased patient-perceived quality of care (b = 2.27; SE = 1.16; P
      = .05; Cohen d = 0.19). There was a significant interaction between patient and
      clinician dosage (b = 7.40; SE = 3.56; P = .04; Cohen d = 0.62), with the
      greatest benefit when both obtained the recommended dosage. Conclusions and
      Relevance: The clinician intervention could improve SDM with minority
      populations, and the patient intervention could augment patient-reported quality
      of care. Trial Registration: clinicaltrials.gov Identifier: NCT01947283.

PMID- 29466537
TI  - Cultural Sensitivity in Deployed US Medical Personnel.

PMID- 29466536
TI  - Association of Time to Attrition in Surgical Residency With Individual Resident
      and Programmatic Factors.
AB  - Importance: Attrition in general surgery residency remains high, and attrition
      that occurs in the later years is the most worrisome. Although several studies
      have retrospectively investigated the timing of attrition, no study to date has
      prospectively evaluated a national cohort of residents to understand which
      residents are at risk for attrition and at what point during residency.
      Objective: To prospectively evaluate individual resident and programmatic factors
      associated with the timing of attrition during general surgery residency. Design,
      Setting, and Participants: This longitudinal, national cohort study administered
      a survey to all categorical general surgery interns from the class of 2007-2008
      during their first 30 days of residency and linked the data with 9-year follow-up
      data assessing program completion. Data were collected from June 1, 2007, through
      June 30, 2016. Main Outcomes and Measures: Kaplan-Meier curves evaluating time to
      attrition during the 9 years after the start of residency. Results: Among our
      sample of 836 residents (306 women [36.6%] and 528 men [63.2%]; gender unknown in
      2), cumulative survival analysis demonstrated overall attrition for the cohort of
      20.8% (n = 164). Attrition was highest in the first postgraduate year (67.6% [n =
      111]; absolute rate, 13.3%) but continued during the next 6 years, albeit at a
      lower rate. Beginning in the first year, survival analysis demonstrated higher
      attrition among Hispanic compared with non-Hispanic residents (21.1% vs 12.4%; P
      = .04) and at military programs compared with academic or community programs
      after year 1 (32.3% vs 11.0% or 13.5%; P = .01). Beginning in year 4 of
      residency, higher attrition was encountered among women compared with men (23.3%
      vs 17.4%; P = .05); at year 5, at large compared with small programs (26.0% vs
      18.4%; P = .04). Race and program location were not associated with attrition.
      Conclusions and Relevance: Although attrition was highest during the internship
      year, late attrition persists, particularly among women and among residents in
      large programs. These results provide a framework for timing of interventions in
      graduate surgical training that target residents most at risk for late attrition.

PMID- 29466535
TI  - Cross-Linguistic Cognate Production in Spanish-English Bilingual Children With
      and Without Specific Language Impairment.
AB  - Purpose: Bilinguals tend to produce cognates (e.g., telephone in English and
      telefono in Spanish) more accurately than they produce noncognates (table/mesa).
      We tested whether the same holds for bilingual children with specific language
      impairment (SLI). Method: Participants included Spanish-English bilingual
      children (aged 5;0 to 9;11 [years;months]), 25 with SLI and 92 without, who had
      comparable language experience. Cognate and noncognate items were taken from
      English and Spanish versions of the Expressive One-Word Picture Vocabulary Test
      (Brownell, 2000, 2001). Results: Although bilingual children with language
      impairment named fewer items correctly overall, they accurately named cognates
      more often than noncognates, as did typically developing children. Independent of
      language ability, accurate naming of a cognate in one language strongly predicted
      accurate naming in the other language. Conclusion: Language impairment appears
      unrelated to the mechanism that produces a cognate advantage in naming accuracy.
      Given that correct performance for a difficult word in one language is associated
      with knowing its cognate in another, cognates may be particularly viable targets
      for language intervention in bilingual children with SLI.

PMID- 29466538
TI  - Progression in a Patient With Previously Treated Atherosclerotic Disease.

PMID- 29466540
TI  - The 2017 American College of Cardiology/American Heart Association Clinical
      Practice Guideline for High Blood Pressure in Adults.

PMID- 29466539
TI  - Management of Recurrent Vestibular Neuritis in a Patient Treated for Rheumatoid
      Arthritis.
AB  - Purpose: This clinical report is presented to describe how results of vestibular
      function testing were considered along with other medical history to develop a
      management plan that was ultimately successful. Method: The patient underwent
      audio-vestibular assessment including comprehensive audiogram,
      videonystagmography, cervical vestibular evoked myogenic potential, and postural
      stability testing. Results: Results from initial testing were most consistent
      with uncompensated peripheral vestibular dysfunction affecting the right superior
      vestibular nerve. These results, considered along with history and symptoms,
      supported vestibular neuritis. After a second vertigo event, we became concerned
      about the potential temporal association between the patient's rheumatoid
      arthritis treatment and symptom onset. It is established that treatment for
      rheumatoid arthritis can exacerbate latent viral issues, but this has not
      specifically been reported for vestibular neuritis. There are reports in the
      literature in which patients successfully used viral suppressant medication to
      decrease viral activity while they were able to continue benefiting from
      immunosuppressive therapy. We hypothesized that, if the current patient's
      vestibular neuritis events were related to her treatment for rheumatoid
      arthritis, she may also benefit from use of viral suppressant medication while
      continuing her otherwise successful immunosuppressive intervention. Conclusions:
      Patients treated with biologic disease-modifying antirheumatic drugs are more
      susceptible to viral issues, and this may include vestibular neuritis. For the
      current case, identifying this possibility and recommending viral suppressant
      medication allowed her to continue with successful treatment of rheumatoid
      arthritis while avoiding additional vertigo events.

PMID- 29466541
TI  - Surgical Training Is a 2-Way Street-The Faculty-Resident Entrustability Dynamic.

PMID- 29466542
TI  - Accuracy of Dermoscopic Criteria for the Diagnosis of Melanoma In Situ.
AB  - Importance: The accuracy of melanoma-specific dermoscopic criteria has been
      tested mainly in studies including invasive tumors. Scarce evidence exists on the
      usefulness of these criteria for the diagnosis of melanoma in situ (MIS).
      Objective: To investigate the diagnostic accuracy of dermoscopic criteria for the
      diagnosis of MIS. Design, Setting, and Participants: A diagnostic accuracy study
      with retrospective patient enrollment was conducted in 3 centers specializing in
      skin cancer diagnosis and management. A total of 1285 individuals with
      histopathologically diagnosed MIS or other flat, pigmented skin tumors that were
      histopathologically diagnosed or monitored for at least 1 year were included.
      Dermoscopic images of MIS and other flat, pigmented skin tumors were evaluated by
      3 independent investigators for the presence of predefined criteria. Evaluators
      were blinded to the clinic dermoscopic and histopathologic diagnosis. Main
      Outcomes and Measures: Frequencies of dermoscopic criteria per diagnosis were
      calculated. Crude odds ratios, adjusted odds ratios, and corresponding 95% CIs
      were calculated by univariate and multivariate logistic regression, respectively.
      Results: A total of 1285 patients were included in the study (642 [50%] male);
      mean age was 45.9 years (range, 9-91 years). Of a total of 1285 lesions obtained
      from these patients, 325 (25.3%) were MIS; 574 (44.7%) were nevi (312 [24.3%]
      excised and 262 [20.4%] not excised); 67 (5.2%) were seborrheic keratoses, solar
      lentigines, or lichen planus-like keratoses; 91 (7.1%) were pigmented superficial
      basal cell carcinomas; 26 (2.0%) were pigmented intraepithelial carcinomas; 100
      (7.8%) were Reed nevi; and 102 (7.9%) were invasive melanomas with a Breslow
      thickness less than 0.75 mm. The most frequent dermoscopic criteria for MIS were
      regression (302 [92.9%]), atypical network (278 [85.5%]), and irregular dots
      and/or globules (163 [50.2%]). The multivariate analysis revealed 5 main positive
      dermoscopic indicators of MIS: atypical network (3.7-fold; 95% CI, 2.5-5.4),
      regression (4.7-fold; 95% CI, 2.8-8.1), irregular hyperpigmented areas (5.4-fold;
      95% CI, 3.7-8.0), prominent skin markings (3.4-fold; 95% CI, 1.9-6.1), and
      angulated lines (2.2-fold; 95% CI, 1.2-4.1). When compared only with excised
      nevi, 2 of these criteria remained potent MIS indicators, namely, irregular
      hyperpigmented areas (4.3-fold; 95% CI, 2.7-6.8) and prominent skin markings (2.7
      fold; 95% CI, 1.3-5.7). Conclusions and Relevance: Clinicians should take into
      consideration the aforementioned dermoscopic indicators for the diagnosis of MIS.

PMID- 29466543
TI  - Ventricular Fibrillation.

PMID- 29466544
TI  - Mepolizumab Treatment of Pediatric Eosinophilic Granulomatosis With Polyangiitis.

PMID- 29466545
TI  - Author Response to Sabour (2018), "Comment on Hall et al. (2017), 'How to Choose
      Between Measures of Tinnitus Loudness for Clinical Research? A Report on the
      Reliability and Validity of an Investigator-Administered Test and a Patient
      Reported Measure Using Baseline Data Collected in a Phase IIa Drug Trial'".
AB  - Purpose: The authors respond to a letter to the editor (Sabour, 2018) concerning
      the interpretation of validity in the context of evaluating treatment-related
      change in tinnitus loudness over time. Method: The authors refer to several
      landmark methodological publications and an international standard concerning the
      validity of patient-reported outcome measurement instruments. Results: The
      tinnitus loudness rating performed better against our reported acceptability
      criteria for (face and convergent) validity than did the tinnitus loudness
      matching test. Conclusion: It is important to distinguish between tests that
      evaluate the validity of measuring treatment-related change over time and tests
      that quantify the accuracy of diagnosing tinnitus as a case and non-case.

PMID- 29466546
TI  - Association of Hidradenitis Suppurativa With Body Image.
AB  - Importance: Hidradenitis suppurativa (HS) leads to disfigurement and painful
      eruptions in terminal hair follicles of the intertriginous skin, mainly of
      axillary, genitofemoral, and perianal sites. It is associated with an excessive
      impairment of quality of life, psychiatric disorders, and sexual distress. Body
      image impairment has been linked to depression and anxiety and has been described
      for some dermatologic disorders but has not yet been investigated in patients
      with HS. Objectives: To investigate whether body image is diminished in patients
      with HS and whether disease severity, age at onset, disease duration, obesity,
      depression, and anxiety are linked to body image impairment. Design, Setting, and
      Participants: This 12-month (August 1, 2009, to August 31, 2010) case-control
      study with a prospective, observational, cross-sectional design recruited 47
      consecutive patients with HS entering a tertiary care center and 45 healthy
      control individuals matched for age, sex, and body mass index (BMI). One patient
      and 4 controls failed to complete the questionnaire and were excluded from the
      evaluation. Data analysis was performed from December 1, 2013, to February 15,
      2014. Main Outcomes and Measures: The Frankfurt Body Concept Scale (FKKS) and the
      Hospital Anxiety and Depression Scale (HADS) were given to patients and controls.
      Correlations among FKKS, HADS, and disease features were calculated. Results: Of
      the 46 patients and 41 controls included in the evaluation (mean [SD] age, 35.6
      [1.6] years; 40 [46%] male and 47 [54%] female), HS significantly reduced body
      image (mean FKKS score, 234.2 [5.4] in patients and 276.9 [5.7] in controls; P <
      .001), even when controlled for BMI. A correlation was found for the extent of
      body image disruption and BMI (r = -0.589; P < .001), HADS-depression score (r = 
      0.619; P < .001), and HADS-anxiety score (r = -0.340; P = .03). No association
      was found for the body image score and the severity of HS, age at onset of
      disease, and duration of disease. The body contact subscale score was the only
      subscale score that was not different between patients with HS and controls.
      Conclusions and Relevance: Patients with HS have major body image impairment,
      which might lead to depression and anxiety, disorders that have been largely
      acknowledged in HS. This study identified another element of the psychosocial
      burden of patients with HS and reveals that body image could potentially be used
      as an outcome measure in future studies of HS.

PMID- 29466547
TI  - Association of Patient Satisfaction With Medical Scribe Use in an Academic
      Dermatology Practice.

PMID- 29466548
TI  - Left Ventricular Diastolic Dysfunction in Hutchinson-Gilford Progeria Syndrome.

PMID- 29466549
TI  - An International Survey of Assessment Practices for Short-Term and Working Memory
      Deficits in Aphasia.
AB  - Purpose: Recent research has highlighted the clinical relevance of understanding
      the nature of short-term memory (STM) and working memory (WM) deficits in persons
      with aphasia and the way these deficits affect linguistic processing and
      functional communication in activities of daily living. The psychometric
      properties of tests commonly used to identify STM/WM problems in individuals with
      aphasia, however, have been questioned. No previous study has sought to
      investigate assessment practices and attitudes by speech-language pathologists
      involved in aphasia management. Accordingly, the aims of this study were (a) to
      investigate both attitudes toward STM/WM assessment in individuals with aphasia,
      as well as the types and frequency of STM/WM tests used with individuals with
      aphasia, and (b) to explore factors (e.g., educational background) that may
      influence STM/WM assessment practices. Method: Respondents recruited via
      professional and aphasia support organizations completed an online survey. The
      survey elicited information about the respondents' demographic and clinical
      backgrounds and STM/WM assessment clinical practices and views, including
      frequency and preferred use of specific STM/WM tests. Results: The majority of
      respondents reported regular use of STM/WM tests as part of aphasia management.
      Positive attitudes toward STM/WM assessments were also reported. The most popular
      rankings of tests were the Cognitive Linguistic Quick Test (Helm-Estabrooks,
      2001), the Comprehensive Aphasia Test (Swinburn, Porter, & Howard, 2005), and the
      Token Test (McNeil & Prescott, 1978). Results suggested limited knowledge about
      measures that assess self-perceptions of functional memory abilities. Regression
      analyses showed that the frequency of reported STM/WM test use was similar
      between clinicians and dual-role researchers/clinicians, but their attitudes
      toward the value of STM/WM differed. U.S. and UK respondents reported similar
      assessment practices. Conclusions: It is reassuring that STM/WM is taken into
      consideration by clinicians when providing aphasia management. Two of the most
      popular tests, however, have poor psychometric properties, and caution should be
      exercised in clinical decision making. The different value placed on STM/WM
      testing by clinicians and researchers/clinicians has implications for continuing
      professional development.

PMID- 29466550
TI  - Treatment of Phonological Disorder: A Feasibility Study With Focus on Outcome
      Measures.
AB  - Purpose: In a feasibility study for a randomized controlled trial of treatments
      for phonological disorders conducted over a period of 8 months, we examined 6
      clinically relevant outcome measures. We took steps to reduce error variance and
      to maximize systematic variance. Method: Six children received traditional
      treatment (Van Riper, 1939), and 7 received expansion points (Smit, 2000), a
      treatment program with both phonological and traditional elements. Outcome
      measures, which were applied to both word list and conversational samples,
      included percentage of consonants correct (PCC; Shriberg & Kwiatkowski, 1982),
      PCC for late and/or difficult (L/D) consonants and number of L/D consonants
      acquired. Results: In repeated-measures analyses of variance, all measures showed
      significant differences from pretreatment to posttreatment, and the word list
      measures were associated with very high power values. In analyses of covariance
      for between-groups contrasts, the adjusted expansion points mean exceeded the
      adjusted traditional treatment mean for every measure; however, no differences
      reached significance. For the L/D PCC (conversation) measure, the contrast
      between groups was associated with a large effect size. Conclusion: We recommend
      that practitioners use outcome measures related to a word list. We recommend that
      researchers consider using L/D PCC on the basis of conversational samples to
      detect differences among treatment groups. Supplemental Materials:
      https://doi.org/10.23641/asha.5872677.

PMID- 29466551
TI  - How Value-Based Medicare Payments Exacerbate Health Care Disparities.

PMID- 29466552
TI  - Statistical Methodology for the Analysis of Repeated Duration Data in Behavioral
      Studies.
AB  - Purpose: Repeated duration data are frequently used in behavioral studies.
      Classical linear or log-linear mixed models are often inadequate to analyze such
      data, because they usually consist of nonnegative and skew-distributed variables.
      Therefore, we recommend use of a statistical methodology specific to duration
      data. Method: We propose a methodology based on Cox mixed models and written
      under the R language. This semiparametric model is indeed flexible enough to fit
      duration data. To compare log-linear and Cox mixed models in terms of goodness-of
      fit on real data sets, we also provide a procedure based on simulations and
      quantile-quantile plots. Results: We present two examples from a data set of
      speech and gesture interactions, which illustrate the limitations of linear and
      log-linear mixed models, as compared to Cox models. The linear models are not
      validated on our data, whereas Cox models are. Moreover, in the second example,
      the Cox model exhibits a significant effect that the linear model does not.
      Conclusions: We provide methods to select the best-fitting models for repeated
      duration data and to compare statistical methodologies. In this study, we show
      that Cox models are best suited to the analysis of our data set.

PMID- 29466553
TI  - The Effects of Varying Directional Bandwidth in Hearing Aid Users' Preference and
      Speech-in-Noise Performance.
AB  - Purpose: Directional microphone systems are typically used to improve hearing aid
      users' understanding of speech in noise. However, directional microphones also
      increase internal hearing aid noise. The purpose of this study was to investigate
      how varying directional microphone bandwidth affected listening preference and
      speech-in-noise performance. Method: Ten participants with normal hearing and 10
      participants with hearing impairment compared internal noise levels between
      hearing aid memories with 4 different microphone modes: omnidirectional, full
      directional, high-frequency directionality with directional processing above 900
      Hz, and high-frequency directionality with directional processing above 2000 Hz.
      Speech-in-noise performance was measured with each memory for the participants
      with hearing impairment. Results: Participants with normal hearing preferred
      memories with less directional bandwidth. Participants with hearing impairment
      also tended to prefer the memories with less directional bandwidth. However, the
      majority of participants with hearing impairment did not indicate a preference
      between omnidirectional and directional above 2000 Hz memories. Average hearing
      in-noise performance improved with increasing directional bandwidth. Conclusions:
      Most participants preferred memories with less directional bandwidth in quiet.
      Participants with hearing impairment indicated no difference in preference
      between directional above 2000 Hz and the omnidirectional memories. Speech
      recognition in noise performance improved with increasing directional bandwidth.

PMID- 29466554
TI  - Trenchlike Ulcer on a Newborn's Scalp.

PMID- 29466555
TI  - Pitch and Time Processing in Speech and Tones: The Effects of Musical Training
      and Attention.
AB  - Purpose: Musical training is often linked to enhanced auditory discrimination,
      but the relative roles of pitch and time in music and speech are unclear.
      Moreover, it is unclear whether pitch and time processing are correlated across
      individuals and how they may be affected by attention. This study aimed to
      examine pitch and time processing in speech and tone sequences, taking musical
      training and attention into account. Method: Musicians (16) and nonmusicians (16)
      were asked to detect pitch or timing changes in speech and tone sequences and
      make a binary response. In some conditions, the participants were focused on 1
      aspect of the stimulus (directed attention), and in others, they had to pay
      attention to all aspects at once (divided attention). Results: As expected,
      musicians performed better overall. Performance scores on pitch and time tasks
      were correlated, as were performance scores for speech and tonal stimuli, but
      most markedly in musicians. All participants performed better on the directed
      versus divided attention task, but again, musicians performed better than
      nonmusicians. Conclusion: In general, this experiment shows that individuals with
      a better sense of pitch discrimination also have a better sense of timing
      discrimination in the auditory domain. In addition, although musicians perform
      better overall, these results do not support the idea that musicians have an
      added advantage for divided attention tasks. These findings serve to better
      understand how musical training and attention affect pitch and time processing in
      the context of speech and tones and may have applications in special populations.
      Supplemental Material: https://doi.org/10.23641/asha.5895997.

PMID- 29466556
TI  - Acoustic Predictors of Pediatric Dysarthria in Cerebral Palsy.
AB  - Purpose: The objectives of this study were to identify acoustic characteristics
      of connected speech that differentiate children with dysarthria secondary to
      cerebral palsy (CP) from typically developing children and to identify acoustic
      measures that best detect dysarthria in children with CP. Method: Twenty 5-year
      old children with dysarthria secondary to CP were compared to 20 age- and sex
      matched typically developing children on 5 acoustic measures of connected speech.
      A logistic regression approach was used to derive an acoustic model that best
      predicted dysarthria status. Results: Results indicated that children with
      dysarthria secondary to CP differed from typically developing children on
      measures of multiple segmental and suprasegmental speech characteristics. An
      acoustic model containing articulation rate and the F2 range of diphthongs
      differentiated children with dysarthria from typically developing children with
      87.5% accuracy. Conclusion: This study serves as a first step toward developing
      an acoustic model that can be used to improve early identification of dysarthria
      in children with CP.

PMID- 29466557
TI  - Bilingualism and Procedural Learning in Typically Developing Children and
      Children With Language Impairment.
AB  - Purpose: The aim of this study was to investigate whether dual language
      experience affects procedural learning ability in typically developing children
      and in children with specific language impairment (SLI). Method: We examined
      procedural learning in monolingual and bilingual school-aged children (ages 8-12
      years) with and without SLI. The typically developing children (35 monolinguals,
      24 bilinguals) and the children with SLI (17 monolinguals, 10 bilinguals)
      completed a serial reaction time task. Results: The typically developing
      monolinguals and bilinguals exhibited equivalent sequential learning effects, but
      neither group with SLI exhibited learning of sequential patterns on the serial
      reaction time task. Conclusion: Procedural learning does not appear to be
      modified by language experience, supporting the notion that it is a child
      intrinsic language learning mechanism that is minimally malleable to experience.

PMID- 29466558
TI  - In-Hospital ST-Segment Elevation Myocardial Infarction: Improving Diagnosis,
      Triage, and Treatment.
AB  - Importance: In-hospital ST-segment elevation myocardial infarction (STEMI) is a
      unique clinical entity with epidemiology, incidence, and outcomes distinct from
      that of out-of-hospital STEMI and has only within the past 10 years begun to
      receive increased attention and research. Patients with in-hospital STEMI are
      older, have more comorbidities, and more frequently have coagulopathies and
      contraindications for anticoagulation and fibrinolytic therapy. A standardized
      clinical definition of in-hospital STEMI is lacking. The objectives of this
      special communication are to (1) summarize the knowledge base regarding in
      hospital STEMI; (2) review the challenges of diagnosis and treatment of patients
      with in-hospital STEMI; (3) present a standardized clinical definition for in
      hospital STEMI; and (4) provide a quality improvement protocol to improve
      diagnosis, triage, and treatment of patients with in-hospital STEMI.
      Observations: Patients with in-hospital STEMI less frequently present with
      typical angina symptoms, and an electrocardiogram is often obtained owing to
      changes in clinical status, changes on telemetry, or a finding of elevated
      cardiac biomarker. The frequent nontypical presentations often lead to
      substantial delays in the diagnosis of STEMI. Only 34% to 71% of patients with in
      hospital STEMI undergo diagnostic catheterization, and only 22% to 56% undergo
      percutaneous coronary intervention. Even in contemporary reports, some studies
      report in-hospital mortality in the range of 31% to 42%. Three areas of delay in
      the treatment of patients with in-hospital STEMI that merit particular attention
      are (1) delays in electrocardiogram acquisition, (2) delays in electrocardiogram
      interpretation, and (3) delays in activation of existing STEMI systems of care.
      Conclusions and Relevance: Treatment of patients with in-hospital STEMI is more
      complex and challenging than treatment of patients who develop out-of-hospital
      STEMI, leading to delays in diagnosis and triage and less frequent use of
      reperfusion therapy. Quality improvement programs targeted at decreasing delays
      and streamlining treatment of such patients may improve treatment and outcome.

PMID- 29466559
TI  - Association of Faculty Entrustment With Resident Autonomy in the Operating Room.
AB  - Importance: A critical balance is sought between faculty supervision, appropriate
      resident autonomy, and patient safety in the operating room. Variability in the
      release of supervision during surgery represents a potential safety hazard to
      patients. A better understanding of intraoperative faculty-resident interactions
      is needed to determine what factors influence entrustment. Objective: To assess
      faculty and resident intraoperative entrustment behaviors and to determine
      whether faculty behaviors drive resident entrustability in the operating room.
      Design, Setting, and Participants: This observational study was conducted from
      September 1, 2015, to August 31, 2016, at Michigan Medicine, the University of
      Michigan's health care system. Two surgical residents, 1 medical student, 2
      behavioral research scientists, and 1 surgical faculty member observed surgical
      intraoperative interactions between faculty and residents in 117 cases involving
      28 faculty and 35 residents and rated entrustment behaviors. Without intervening
      in the interaction, 1 or 2 researchers observed each case and noted behaviors,
      verbal and nonverbal communication, and interaction processes. Immediately after
      the case, observers completed an assessment using OpTrust, a validated tool
      designed to assess progressive entrustment in the operating room. Purposeful
      sampling was used to generate variation in type of operation, case difficulty,
      faculty-resident pairings, faculty experience, and resident training level. Main
      Outcomes and Measures: Observer results in the form of entrustability scores
      (range, 1-4, with 4 indicating full entrustability) were compared with resident-
      and faculty-reported measures. Difficulty of operation was rated on a scale of 1
      to 3 (higher scores indicate greater difficulty). Path analysis was used to
      explore direct and indirect effects of the predictors. Associations between
      resident entrustability and observation duration, observation month, and faculty
      entrustment scores were assessed by pairwise Pearson correlation coefficients.
      Results: Twenty-eight faculty and 35 residents were observed across 117 surgical
      cases from 4 surgical specialties. Cases observed by postgraduate year (PGY) of
      residents were distributed as follows: PGY-1, 21 (18%); 2, 15 (13%); 3, 17 (15%);
      4, 27 (23%); 5, 28 (24%); and 6, 9 (8%). Case difficulty was evenly distributed:
      36 (33%) were rated easy/straightforward; 43 (40%), moderately difficult; and 29
      (27%), very difficult by attending physicians. Path analysis showed that the
      association of PGY with resident entrustability was mediated by faculty
      entrustment (0.23 [.03]; P < .001). At the univariate level, case difficulty
      (mean [SD] resident entrustability score range, 1.97 [0.75] for
      easy/straightforward cases to 2.59 [0.82] for very difficult cases; F = 6.69; P =
      .01), PGY (range, 1.31 [0.28] for PGY-1 to 3.16 [0.54] for PGY-6; F = 22.85; P <
      .001), and faculty entrustment (2.27 [0.79]; R2 = 0.91; P < .001) were
      significantly associated with resident entrustability. Mean (SD) resident
      entrustability scores were highest for very difficult cases (2.59 [0.82]) and PGY
      6 (3.16 [0.54]). Conclusions and Relevance: Faculty entrustment behaviors may be
      the primary drivers of resident entrustability. Faculty entrustment is a feature
      of faculty surgeons' teaching style and could be amenable to faculty development
      efforts.

PMID- 29466560
TI  - Comparison of Military and Civilian Methods for Determining Potentially
      Preventable Deaths: A Systematic Review.
AB  - Importance: Military and civilian trauma experts initiated a collaborative effort
      to develop an integrated learning trauma system to reduce preventable morbidity
      and mortality. Because the Department of Defense does not currently have
      recommended guidelines and standard operating procedures to perform military
      preventable death reviews in a consistent manner, these performance improvement
      processes must be developed. Objectives: To compare military and civilian
      preventable death determination methods to understand the existing best practices
      for evaluating preventable death. Evidence Review: This systematic review
      followed the PRISMA reporting guidelines. English-language articles were searched
      from inception to February 15, 2017, using the following databases: MEDLINE
      (Ovid), Evidence-Based Medicine Reviews (Ovid), PubMed, CINAHL, and Google
      Scholar. Articles were initially screened for eligibility and excluded based on
      predetermined criteria. Articles reviewing only prehospital deaths, only
      inhospital deaths, or both were eligible for inclusion. Information on study
      characteristics was independently abstracted by 2 investigators. Reported are
      methodological factors affecting the reliability of preventable death studies and
      the preventable death rate, defined as the number of potentially preventable
      deaths divided by the total number of deaths within a specific patient
      population. Findings: Fifty studies (8 military and 42 civilian) met the
      inclusion criteria. In total, 1598 of 6500 military deaths reviewed and 3346 of
      19 108 civilian deaths reviewed were classified as potentially preventable. Among
      military studies, the preventable death rate ranged from 3.1% to 51.4%. Among
      civilian studies, the preventable death rate ranged from 2.5% to 85.3%. The high
      level of methodological heterogeneity regarding factors, such as preventable
      death definitions, review process, and determination criteria, hinders a
      meaningful quantitative comparison of preventable death rates. Conclusions and
      Relevance: The reliability of military and civilian preventable death studies is
      hindered by inconsistent definitions, incompatible criteria, and the overall
      heterogeneity in study methods. The complexity, inconsistency, and
      unpredictability of combat require unique considerations to perform a
      methodologically sound combat-related preventable death review. As the Department
      of Defense begins the process of developing recommended guidelines and standard
      operating procedures for performing military preventable death reviews,
      consideration must be given to the factors known to increase the risk of bias and
      poor reliability.

PMID- 29466561
TI  - Comment on Hall et al. (2017), "How to Choose Between Measures of Tinnitus
      Loudness for Clinical Research? A Report on the Reliability and Validity of an
      Investigator-Administered Test and a Patient-Reported Measure Using Baseline Data
      Collected in a Phase IIa Drug Trial".
AB  - Purpose: The purpose of this letter, in response to Hall, Mehta, and Fackrell
      (2017), is to provide important knowledge about methodology and statistical
      issues in assessing the reliability and validity of an audiologist-administered
      tinnitus loudness matching test and a patient-reported tinnitus loudness rating.
      Method: The author uses reference textbooks and published articles regarding
      scientific assessment of the validity and reliability of a clinical test to
      discuss the statistical test and the methodological approach in assessing
      validity and reliability in clinical research. Results: Depending on the type of
      the variable (qualitative or quantitative), well-known statistical tests can be
      applied to assess reliability and validity. The qualitative variables of
      sensitivity, specificity, positive predictive value, negative predictive value,
      false positive and false negative rates, likelihood ratio positive and likelihood
      ratio negative, as well as odds ratio (i.e., ratio of true to false results), are
      the most appropriate estimates to evaluate validity of a test compared to a gold
      standard. In the case of quantitative variables, depending on distribution of the
      variable, Pearson r or Spearman rho can be applied. Conclusion: Diagnostic
      accuracy (validity) and diagnostic precision (reliability or agreement) are two
      completely different methodological issues. Depending on the type of the variable
      (qualitative or quantitative), well-known statistical tests can be applied to
      assess validity.

PMID- 29466564
TI  - Validation of the Chinese Sound Test: Auditory Performance of Hearing Aid Users.
AB  - Purpose: The Chinese Sound Test (Hung, Lin, Tsai, & Lee, 2016) has been recently
      developed as a modified version of the Ling Six-Sound Test (Ling, 2012). By
      incorporating Chinese speech sounds, this test should be able to estimate whether
      the listener can hear across the Chinese speech spectrum. To establish the
      clinical validity of the test, this study examined the relationship between the
      aided audiometric thresholds and the distance thresholds. Method: Sixty children
      with bilateral hearing aids were recruited. The aided sound-field thresholds at
      250, 500, 1000, 2000, 4000, and 6000 Hz were compared with the distance
      thresholds of six sounds, /u, e, a, i, tch, and s/, which encompass the entire
      Chinese speech frequency range from low to high. Results: Partial correlation and
      stepwise regression analyses revealed that the Chinese testing sounds are
      frequency specific and that the audibility of each sound could be predicted by a
      specific frequency threshold. Conclusions: The results confirm the validity of
      the Chinese Sound Test, indicating that the testing sounds can be reliably used
      to assess the perception of frequency-specific information. Crucially, these data
      also demonstrate that the Chinese Sound Test is a useful tool to identify red
      flags of poor auditory access in daily environment to monitor device malfunctions
      and possible hearing fluctuations.

PMID- 29466567
TI  - Dermoscopy and Overdiagnosis of Melanoma In Situ.

PMID- 29466569
TI  - Omitted Conflict of Interest Disclosures.

PMID- 29466568
TI  - Incorrect Data in Tables.

PMID- 29466570
TI  - Error in Figure.

PMID- 29466571
TI  - Disentangling Health Care Billing: For Patients' Physical and Financial Health.

PMID- 29466572
TI  - Time to Rethink the Approach to Treating Acute Respiratory Distress Syndrome.

PMID- 29466574
TI  - Notable Year for Novel Drugs.

PMID- 29466573
TI  - Preventing Delirium in the Intensive Care Unit.

PMID- 29466575
TI  - Diabetic Foot Ulcers Heal With Shock Wave Therapy.

PMID- 29466576
TI  - Crackdown on Stem Cell Product.

PMID- 29466577
TI  - Management of ARDS in Adults.

PMID- 29466579
TI  - The Problem With Work Requirements for Medicaid.

PMID- 29466580
TI  - Medical Research and the Golden Rule: Michael E. De Bakey, MD.

PMID- 29466581
TI  - Prevalence of Housing Problems Among Community Health Center Patients.

PMID- 29466582
TI  - Organ Dysfunction After Surgery in Patients Treated With Individualized or
      Standard Blood Pressure Management.

PMID- 29466583
TI  - Organ Dysfunction After Surgery in Patients Treated With Individualized or
      Standard Blood Pressure Management.

PMID- 29466584
TI  - Organ Dysfunction After Surgery in Patients Treated With Individualized or
      Standard Blood Pressure Management.

PMID- 29466585
TI  - Organ Dysfunction After Surgery in Patients Treated With Individualized or
      Standard Blood Pressure Management.

PMID- 29466586
TI  - Authorship Credit for Large Clinical Trials.

PMID- 29466587
TI  - Organ Dysfunction After Surgery in Patients Treated With Individualized or
      Standard Blood Pressure Management.

PMID- 29466588
TI  - Authorship Credit for Large Clinical Trials-Reply.

PMID- 29466589
TI  - Organ Dysfunction After Surgery in Patients Treated With Individualized or
      Standard Blood Pressure Management-Reply.

PMID- 29466590
TI  - Administrative Costs Associated With Physician Billing and Insurance-Related
      Activities at an Academic Health Care System.
AB  - Importance: Administrative costs in the US health care system are an important
      component of total health care spending, and a substantial proportion of these
      costs are attributable to billing and insurance-related activities. Objective: To
      examine and estimate the administrative costs associated with physician billing
      activities in a large academic health care system with a certified electronic
      health record system. Design, Setting, and Participants: This study used time
      driven activity-based costing. Interviews were conducted with 27 health system
      administrators and 34 physicians in 2016 and 2017 to construct a process map
      charting the path of an insurance claim through the revenue cycle management
      process. These data were used to calculate the cost for each major billing and
      insurance-related activity and were aggregated to estimate the health system's
      total cost of processing an insurance claim. Exposures: Estimated time required
      to perform billing and insurance-related activities, based on interviews with
      management personnel and physicians. Main Outcomes and Measures: Estimated
      billing and insurance-related costs for 5 types of patient encounters: primary
      care visits, discharged emergency department visits, general medicine inpatient
      stays, ambulatory surgical procedures, and inpatient surgical procedures.
      Results: Estimated processing time and total costs for billing and insurance
      related activities were 13 minutes and $20.49 for a primary care visit, 32
      minutes and $61.54 for a discharged emergency department visit, 73 minutes and
      $124.26 for a general inpatient stay, 75 minutes and $170.40 for an ambulatory
      surgical procedure, and 100 minutes and $215.10 for an inpatient surgical
      procedure. Of these totals, time and costs for activities carried out by
      physicians were estimated at a median of 3 minutes or $6.36 for a primary care
      visit, 3 minutes or $10.97 for an emergency department visit, 5 minutes or $13.29
      for a general inpatient stay, 15 minutes or $51.20 for an ambulatory surgical
      procedure, and 15 minutes or $51.20 for an inpatient surgical procedure. Of
      professional revenue, professional billing costs were estimated to represent
      14.5% for primary care visits, 25.2% for emergency department visits, 8.0% for
      general medicine inpatient stays, 13.4% for ambulatory surgical procedures, and
      3.1% for inpatient surgical procedures. Conclusions and Relevance: In a time
      driven activity-based costing study in a large academic health care system with a
      certified electronic health record system, the estimated costs of billing and
      insurance-related activities ranged from $20 for a primary care visit to $215 for
      an inpatient surgical procedure. Knowledge of how specific billing and insurance
      related activities contribute to administrative costs may help inform policy
      solutions to reduce these expenses.

PMID- 29466593
TI  - Acute Respiratory Distress Syndrome.

PMID- 29466591
TI  - Effect of Haloperidol on Survival Among Critically Ill Adults With a High Risk of
      Delirium: The REDUCE Randomized Clinical Trial.
AB  - Importance: Results of studies on use of prophylactic haloperidol in critically
      ill adults are inconclusive, especially in patients at high risk of delirium.
      Objective: To determine whether prophylactic use of haloperidol improves survival
      among critically ill adults at high risk of delirium, which was defined as an
      anticipated intensive care unit (ICU) stay of at least 2 days. Design, Setting,
      and Participants: Randomized, double-blind, placebo-controlled investigator
      driven study involving 1789 critically ill adults treated at 21 ICUs, at which
      nonpharmacological interventions for delirium prevention are routinely used in
      the Netherlands. Patients without delirium whose expected ICU stay was at least a
      day were included. Recruitment was from July 2013 to December 2016 and follow-up
      was conducted at 90 days with the final follow-up on March 1, 2017.
      Interventions: Patients received prophylactic treatment 3 times daily
      intravenously either 1 mg (n = 350) or 2 mg (n = 732) of haloperidol or placebo
      (n = 707), consisting of 0.9% sodium chloride. Main Outcome and Measures: The
      primary outcome was the number of days that patients survived in 28 days. There
      were 15 secondary outcomes, including delirium incidence, 28-day delirium-free
      and coma-free days, duration of mechanical ventilation, and ICU and hospital
      length of stay. Results: All 1789 randomized patients (mean, age 66.6 years [SD,
      12.6]; 1099 men [61.4%]) completed the study. The 1-mg haloperidol group was
      prematurely stopped because of futility. There was no difference in the median
      days patients survived in 28 days, 28 days in the 2-mg haloperidol group vs 28
      days in the placebo group, for a difference of 0 days (95% CI, 0-0; P = .93) and
      a hazard ratio of 1.003 (95% CI, 0.78-1.30, P=.82). All of the 15 secondary
      outcomes were not statistically different. These included delirium incidence
      (mean difference, 1.5%, 95% CI, -3.6% to 6.7%), delirium-free and coma-free days
      (mean difference, 0 days, 95% CI, 0-0 days), and duration of mechanical
      ventilation, ICU, and hospital length of stay (mean difference, 0 days, 95% CI, 0
      0 days for all 3 measures). The number of reported adverse effects did not differ
      between groups (2 [0.3%] for the 2-mg haloperidol group vs 1 [0.1%] for the
      placebo group). Conclusions and Relevance: Among critically ill adults at high
      risk of delirium, the use of prophylactic haloperidol compared with placebo did
      not improve survival at 28 days. These findings do not support the use of
      prophylactic haloperidol for reducing mortality in critically ill adults. Trial
      Registration: clinicaltrials.gov Identifier: NCT01785290.

PMID- 29466592
TI  - Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight
      Adults and the Association With Genotype Pattern or Insulin Secretion: The
      DIETFITS Randomized Clinical Trial.
AB  - Importance: Dietary modification remains key to successful weight loss. Yet, no
      one dietary strategy is consistently superior to others for the general
      population. Previous research suggests genotype or insulin-glucose dynamics may
      modify the effects of diets. Objective: To determine the effect of a healthy low
      fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change and if
      genotype pattern or insulin secretion are related to the dietary effects on
      weight loss. Design, Setting, and Participants: The Diet Intervention Examining
      The Factors Interacting with Treatment Success (DIETFITS) randomized clinical
      trial included 609 adults aged 18 to 50 years without diabetes with a body mass
      index between 28 and 40. The trial enrollment was from January 29, 2013, through
      April 14, 2015; the date of final follow-up was May 16, 2016. Participants were
      randomized to the 12-month HLF or HLC diet. The study also tested whether 3
      single-nucleotide polymorphism multilocus genotype responsiveness patterns or
      insulin secretion (INS-30; blood concentration of insulin 30 minutes after a
      glucose challenge) were associated with weight loss. Interventions: Health
      educators delivered the behavior modification intervention to HLF (n = 305) and
      HLC (n = 304) participants via 22 diet-specific small group sessions administered
      over 12 months. The sessions focused on ways to achieve the lowest fat or
      carbohydrate intake that could be maintained long-term and emphasized diet
      quality. Main Outcomes and Measures: Primary outcome was 12-month weight change
      and determination of whether there were significant interactions among diet type
      and genotype pattern, diet and insulin secretion, and diet and weight loss.
      Results: Among 609 participants randomized (mean age, 40 [SD, 7] years; 57%
      women; mean body mass index, 33 [SD, 3]; 244 [40%] had a low-fat genotype; 180
      [30%] had a low-carbohydrate genotype; mean baseline INS-30, 93 MUIU/mL), 481
      (79%) completed the trial. In the HLF vs HLC diets, respectively, the mean 12
      month macronutrient distributions were 48% vs 30% for carbohydrates, 29% vs 45%
      for fat, and 21% vs 23% for protein. Weight change at 12 months was -5.3 kg for
      the HLF diet vs -6.0 kg for the HLC diet (mean between-group difference, 0.7 kg
      [95% CI, -0.2 to 1.6 kg]). There was no significant diet-genotype pattern
      interaction (P = .20) or diet-insulin secretion (INS-30) interaction (P = .47)
      with 12-month weight loss. There were 18 adverse events or serious adverse events
      that were evenly distributed across the 2 diet groups. Conclusions and Relevance:
      In this 12-month weight loss diet study, there was no significant difference in
      weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet,
      and neither genotype pattern nor baseline insulin secretion was associated with
      the dietary effects on weight loss. In the context of these 2 common weight loss
      diet approaches, neither of the 2 hypothesized predisposing factors was helpful
      in identifying which diet was better for whom. Trial Registration:
      clinicaltrials.gov Identifier: NCT01826591.

PMID- 29466595
TI  - A Teaching Case.

PMID- 29466596
TI  - Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment.
AB  - Importance: Acute respiratory distress syndrome (ARDS) is a life-threatening form
      of respiratory failure that affects approximately 200 000 patients each year in
      the United States, resulting in nearly 75 000 deaths annually. Globally, ARDS
      accounts for 10% of intensive care unit admissions, representing more than 3
      million patients with ARDS annually. Objective: To review advances in diagnosis
      and treatment of ARDS over the last 5 years. Evidence Review: We searched
      MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 2012 to
      2017 focusing on randomized clinical trials, meta-analyses, systematic reviews,
      and clinical practice guidelines. Articles were identified for full text review
      with manual review of bibliographies generating additional references. Findings:
      After screening 1662 citations, 31 articles detailing major advances in the
      diagnosis or treatment of ARDS were selected. The Berlin definition proposed 3
      categories of ARDS based on the severity of hypoxemia: mild (200 mm
      Hg<Pao2/Fio2<=300 mm Hg), moderate (100 mm Hg<Pao2/Fio2<=200 mm Hg), and severe
      (Pao2/Fio2 <=100 mm Hg), along with explicit criteria related to timing of the
      syndrome's onset, origin of edema, and the chest radiograph findings. The Berlin
      definition has significantly greater predictive validity for mortality than the
      prior American-European Consensus Conference definition. Clinician interpretation
      of the origin of edema and chest radiograph criteria may be less reliable in
      making a diagnosis of ARDS. The cornerstone of management remains mechanical
      ventilation, with a goal to minimize ventilator-induced lung injury (VILI).
      Aspirin was not effective in preventing ARDS in patients at high-risk for the
      syndrome. Adjunctive interventions to further minimize VILI, such as prone
      positioning in patients with a Pao2/Fio2 ratio less than 150 mm Hg, were
      associated with a significant mortality benefit whereas others (eg,
      extracorporeal carbon dioxide removal) remain experimental. Pharmacologic
      therapies such as beta2 agonists, statins, and keratinocyte growth factor, which
      targeted pathophysiologic alterations in ARDS, were not beneficial and
      demonstrated possible harm. Recent guidelines on mechanical ventilation in ARDS
      provide evidence-based recommendations related to 6 interventions, including low
      tidal volume and inspiratory pressure ventilation, prone positioning, high
      frequency oscillatory ventilation, higher vs lower positive end-expiratory
      pressure, lung recruitment maneuvers, and extracorporeal membrane oxygenation.
      Conclusions and Relevance: The Berlin definition of acute respiratory distress
      syndrome addressed limitations of the American-European Consensus Conference
      definition, but poor reliability of some criteria may contribute to
      underrecognition by clinicians. No pharmacologic treatments aimed at the
      underlying pathology have been shown to be effective, and management remains
      supportive with lung-protective mechanical ventilation. Guidelines on mechanical
      ventilation in patients with acute respiratory distress syndrome can assist
      clinicians in delivering evidence-based interventions that may lead to improved
      outcomes.

PMID- 29466598
TI  - Inflammatory Bowel Disease Goes Global.

PMID- 29466599
TI  - High Rates of Violent Death Among Rohingya Refugees.

PMID- 29466600
TI  - Air Pollutants Undermine Infant Brain Development.

PMID- 29466601
TI  - Delayed cone-opponent signals in the luminance pathway.
AB  - Cone signals in the luminance or achromatic pathway were investigated by
      measuring how the perceptual timing of M- or L-cone-detected flicker depended on
      temporal frequency and chromatic adaptation. Relative timings were measured, as a
      function of temporal frequency, by superimposing M- or L-cone-isolating flicker
      on "equichromatic" flicker (flicker of the same wavelength as the background) and
      asking observers to vary contrast and phase to cancel the perception of flicker.
      Measurements were made in four observers on up to 35 different backgrounds
      varying in wavelength and radiance. Observers showed substantial perceptual
      delays or advances of L- and M-cone flicker that varied systematically with cone
      class, background wavelength, and radiance. Delays were largest for M-cone
      isolating flicker. Although complex, the results can be characterised by a
      surprisingly simple model in which the representations of L- and M-cone flicker
      are comprised not only of a fast copy of the flicker signal, but also of a slow
      copy that is delayed by roughly 30 ms and varies in strength and sign with both
      background wavelength and radiance. The delays, which are too large to be due to
      selective cone adaptation by the chromatic backgrounds, must arise
      postreceptorally. Clear evidence for the slow signals can also be found in
      physiological measurements of horizontal and magnocellular ganglion cells, thus
      placing the origin of the slow signals in the retina-most likely in an extended
      horizontal cell network. Luminance-equated stimuli chosen to isolate chromatic
      channels may inadvertently generate slow signals in the luminance channel.

PMID- 29466602
TI  - Flavonoids from Trollius europaeus flowers and evaluation of their biological
      activity.
AB  - OBJECTIVES: This article describes the flavonoid composition of the flowers of
      Trollius europaeus and the method of isolation thereof and provides an attempt at
      investigating the antioxidant activity of the isolated flavonoids and the
      antityrosinase activity of the extracts from the investigated material. METHODS:
      The compositional data were acquired by combining results of nuclear magnetic
      resonance, ultraviolet spectroscopy, electrospray ionisation-tandem mass
      spectrometry (ESI-MS/MS) analyses and those of an analysis of the products of
      acid hydrolysis of the compounds. The antioxidant activity of the extracts was
      studied using the 2,2'-diphenyl-1-picrylhydrazyl assay and the tyrosinase
      inhibitory activity - with the use of mushroom tyrosinase. KEY FINDINGS: Ten
      flavonoid derivatives of luteolin and apigenin were isolated from the flowers of
      T. europaeus and identified. The investigation into the antioxidant activity
      revealed that orientin 2"-O-alpha-arabinopyranoside (4) and orientin 2"-O-beta
      glucopyranoside (5) had a significant antioxidant effect. CONCLUSIONS: The
      studies conducted led to the development of a method of isolating flavonoid,
      potentially antioxidant, compounds from T. europaeus. They allowed to determine
      which of the investigated flavonoids demonstrated significant antioxidant
      activity and could be used as natural antioxidants.

PMID- 29466603
TI  - Temperature-dependent oxygen limitation and the rise of Bergmann's rule in
      species with aquatic respiration.
AB  - Bergmann's rule is the propensity for species-mean body size to decrease with
      increasing temperature. Temperature-dependent oxygen limitation has been
      hypothesized to help drive temperature-size relationships among ectotherms,
      including Bergmann's rule, where organisms reduce body size under warm oxygen
      limited conditions, thereby maintaining aerobic scope. Temperature-dependent
      oxygen limitation should be most pronounced among aquatic ectotherms that cannot
      breathe aerially, as oxygen solubility in water decreases with increasing
      temperature. We use phylogenetically explicit analyses to show that species-mean
      adult size of aquatic salamanders with branchial or cutaneous oxygen uptake
      becomes small in warm environments and large in cool environments, whereas body
      size of aquatic species with lungs (i.e., that respire aerially), as well as size
      of semiaquatic and terrestrial species do not decrease with temperature. We argue
      that oxygen limitation drives the evolution of small size in warm aquatic
      environments for species with aquatic respiration. More broadly, the stronger
      decline in size with temperature observed in aquatic versus terrestrial
      salamander species mirrors the relatively strong plastic declines in size
      observed previously among aquatic versus terrestrial invertebrates, suggesting
      that temperature-dependent oxygen availability can help drive patterns of
      plasticity, micro- and macroevolution.

PMID- 29466604
TI  - Combined AC-electrokinetic effects: Theoretical considerations on a three-axial
      ellipsoidal model.
AB  - AC fields induce charges at the structural interfaces of particles or biological
      cells. The interaction of these charges with the field generates frequency
      dependent forces that are the basis for AC-electrokinetic effects such as
      dielectrophoresis (DEP), electrorotation (ROT), electro-orientation, and electro
      deformation. The effects can be used for the manipulation or dielectric single
      particle spectroscopy. The observation of a particular effect depends on the
      spatial and temporal field distributions, as well as on the shape and the
      dielectric and viscoelastic properties of the object. Because the effects are not
      mutually independent, combined frequency spectra are obtained, for example,
      discontinuous DEP and ROT spectra with ranges separated by the reorientation of
      nonspherical objects in the linearly and circularly polarized DEP and ROT fields,
      respectively. As an example, the AC electrokinetic behavior of a three-axial
      ellipsoidal single-shell model with the geometry of chicken-red blood cells is
      considered. The geometric and electric problems were separated using the
      influential-radius approach. The obtained finite-element model can be
      electrically interpreted by an RC model leading to an expression for the Clausius
      Mossotti factor, which permits the derivation of force, torque, and orientation
      spectra, as well as of equations for the critical frequencies and force plateaus
      in DEP and of the characteristic frequencies and peak heights in ROT. Expressions
      for the orientation in linearly and circularly polarized fields, as well as for
      the reorientation frequencies were also derived. The considerations suggested
      that the simultaneous registration of various AC-electrokinetic spectra is a step
      towards the dielectric fingerprinting of single objects.

PMID- 29466605
TI  - Continuous sheath-free separation of drug-treated human fungal pathogen
      Cryptococcus neoformans by morphology in biocompatible polymer solutions.
AB  - Cryptococcal meningitis caused by Cryptococcus neoformans is the leading cause of
      fungal central nervous system infections. Current antifungal treatments for
      cryptococcal infections are inadequate partly due to the occurrence of drug
      resistance. Recent studies indicate that the treatment of the azole drug
      fluconazole changes the morphology of C. neoformans to form enlarged "multimeras"
      that consist of three or more connected cells/buds. To analyze if these
      multimeric cells are a prerequisite for C. neoformans to acquire drug resistance,
      a tool capable of separating them from normal cells is critical. We extend our
      recently demonstrated sheath-free elasto-inertial particle separation technique
      to fractionate drug-treated C. neoformans cells by morphology in biocompatible
      polymer solutions. The separation performance is evaluated for both multimeric
      and normal cells in terms of three dimensionless metrics: efficiency, purity, and
      enrichment ratio. The effects of flow rate, polymer concentration, and
      microchannel height on cell separation are studied.

PMID- 29466606
TI  - Using Attachment to Better Understand the Therapy Alliance: The Attachment Based
      Alliance Questionnaire.
AB  - Questionnaires on the therapeutic alliance are available, but most show inflated
      scores, limited variability, and few significant findings on the bonds domain.
      Results of a study of 251 clinical couples, on the development of an Attachment
      Based Alliance Questionnaire (ABAQ), are presented. Factor analysis (EFA and
      CFA), show that a one-factor or two-factor structure fit the data, with more
      support for a one-factor model. Both models map closely with attachment
      constructs. Results also show that the ABAQ is predictive of changes couples make
      early in therapy and demonstrated adequate reliability and validity. The ABAQ
      provides a tool for clinicians as they learn how to attune to relationships in
      couple therapy and is helpful to researchers in understanding the alliance.

PMID- 29466607
TI  - (Multi-)Metallic Cluster Growth.
AB  - This review article provides a survey of contemporary investigations on main
      group metal cluster formation, addressing homo- and heterometallic clusters
      (including small numbers of transition metal atoms), with or without an external
      ligand shell, thereby excluding clusters with non-metal atoms as bridging
      ligands. Most of the studies reflected herein represent insights into the
      formation of intermediates from the starting material, or the final cluster
      formation from established intermediates. In rare cases, the entire process was
      suggested as a result of comprehensive, multi-method elucidations. The article is
      to be understood as a state-of-the-art report, as the subject matter is currently
      a rising field of research, which is still in its infancy, despite some early
      activities that date back to the 1980s. At the same time, the article intends to
      point toward both the importance and the feasibility of according studies, in
      order to encourage researchers to gain even more knowledge in this field. Only
      deep understanding of cluster formation will allow for design, and ultimately
      control, of their syntheses, with the long-term goal of their optimization and
      purposeful application in catalysis or novel material synthesis.

PMID- 29466608
TI  - Blood pressure variability and neurocognitive functioning.

PMID- 29466609
TI  - A comparison of metacognitive factors among patients with cancer and the control
      group.
AB  - OBJECTIVE: Research examining the relationship between metacognitions and cancer
      has only recently begun to emerge. This study attempted to compare the
      metacognitions of the patients with and without cancer. The effects of stage of
      cancer, type of cancer, and treatment modality (chemotherapy, radiotherapy,
      operation) on metacognitions were investigated. Patients with cancer were
      hypothesized to have higher levels of negative metacognitions. METHODS:
      Participants were patients with cancer (N = 279) and patients without cancer
      (control group, N = 212). The Metacognition Questionnaire-30 was administered to
      all participants. Results were analyzed according to demographic and
      histopathological characteristics of the patients. RESULTS: The results showed
      that patients with different cancer diagnoses scored higher than the controls on
      all subscales of the MCQ-30. Those who received chemotherapy scored the highest
      on the MCQ-30. The patients who were in early stages of cancer had higher levels
      of negative metacognitions. Patients who did not have operation but had
      chemotherapy had the highest levels of negative metacognitions. Patients who were
      in locally advanced stage, did not have operation but had received or was
      receiving chemotherapy had the highest levels of negative metacognitions.
      CONCLUSIONS: Patients who were in early stages of cancer appeared to be in
      greater need for psychological help and access to services. Findings indicated a
      need for psychological support for patients who undergo chemotherapy.

PMID- 29466610
TI  - Preparation of bio-based keratin-derived magnetic molecularly imprinted polymer
      nanoparticles for the facile and selective separation of bisphenol A from water.
AB  - In this study, new bio-based magnetic molecularly imprinted polymer nanoparticles
      (~23 nm) were synthesized from keratin extracted from chicken feathers and
      methacrylate-functionalized Fe3 O4 nanoparticles for its potential application in
      separation and removal of bisphenol A from water. The prepared magnetic
      molecularly imprinted polymer was characterized by Fourier-transform infrared
      spectroscopy, field-emission scanning electron microscopy, thermogravimetric
      analysis, alternative gradient field magnetometry, and energy-dispersive X-ray
      spectroscopy. The sorption of bisphenol A was investigated by changing the
      influencing factors such as pH, immersion time, Fe3 O4 nanoparticles dosage, and
      the initial concentration of bisphenol A. Results illustrated that sorption was
      very fast and efficient (Qm  = 600 mg/g) having a removal efficiency of ~98% in
      40 min of immersion. The adsorption process showed better conformity with the
      Weber-Morris kinetics and the Freundlich isotherm model. The selectivity of
      bisphenol A by adsorbent was checked in the presence of hydroquinone, phenol,
      tetrabromobisphenol, and 4,4'-biphenol as interferences.

PMID- 29466612
TI  - Bayesian enhancement two-stage design for single-arm phase II clinical trials
      with binary and time-to-event endpoints.
AB  - Simon's two-stage design is one of the most commonly used methods in phase II
      clinical trials with binary endpoints. The design tests the null hypothesis that
      the response rate is less than an uninteresting level, versus the alternative
      hypothesis that the response rate is greater than a desirable target level. From
      a Bayesian perspective, we compute the posterior probabilities of the null and
      alternative hypotheses given that a promising result is declared in Simon's
      design. Our study reveals that because the frequentist hypothesis testing
      framework places its focus on the null hypothesis, a potentially efficacious
      treatment identified by rejecting the null under Simon's design could have only
      less than 10% posterior probability of attaining the desirable target level. Due
      to the indifference region between the null and alternative, rejecting the null
      does not necessarily mean that the drug achieves the desirable response level. To
      clarify such ambiguity, we propose a Bayesian enhancement two-stage (BET) design,
      which guarantees a high posterior probability of the response rate reaching the
      target level, while allowing for early termination and sample size saving in case
      that the drug's response rate is smaller than the clinically uninteresting level.
      Moreover, the BET design can be naturally adapted to accommodate survival
      endpoints. We conduct extensive simulation studies to examine the empirical
      performance of our design and present two trial examples as applications.

PMID- 29466613
TI  - On-Demand Production of Flow-Reactor Cartridges by 3D Printing of Thermostable
      Enzymes.
AB  - The compartmentalization of chemical reactions is an essential principle of life
      that provides a major source of innovation for the development of novel
      approaches in biocatalysis. To implement spatially controlled biotransformations,
      rapid manufacturing methods are needed for the production of biocatalysts that
      can be applied in flow systems. Whereas three-dimensional (3D) printing
      techniques offer high-throughput manufacturing capability, they are usually not
      compatible with the delicate nature of enzymes, which call for physiological
      processing parameters. We herein demonstrate the utility of thermostable enzymes
      in the generation of biocatalytic agarose-based inks for a simple temperature
      controlled 3D printing process. As examples we utilized an esterase and an
      alcohol dehydrogenase from thermophilic organisms as well as a decarboxylase that
      was thermostabilized by directed protein evolution. We used the resulting 3D
      printed parts for a continuous, two-step sequential biotransformation in a
      fluidic setup.

PMID- 29466614
TI  - Cognitive computing, paired with Genomics, may benefit cancer treatment.

PMID- 29466616
TI  - More municipalities and states raise tobacco purchase age to 21 years: Tobacco
      control advocates begin to see progress.

PMID- 29466615
TI  - Patients with advanced cancer prefer that physicians do not use computers in the
      examination room.

PMID- 29466617
TI  - Synthesis and Characterization of the R27S Genetic Variant of Insulin-like
      Peptide 5.
AB  - We report the synthesis and in vitro bioactivity assessment for an insulin-like
      peptide 5 (INSL5) analogue that was recently discovered as a genetic mutation in
      an Amish population. The mutation was associated with improved metabolic status,
      and receptor-based antagonism was proposed as a potential mechanism for the
      altered phenotype. We determined the specific peptide analogue to be fully potent
      and of maximal efficacy at the human relaxin family peptide receptor 4 (RXFP4),
      suggesting an alternative basis for the observed effect. In preparation of this
      synthetically challenging hormone, we have introduced several improvements such
      as implementation of isoacyl chemistry for high-efficiency preparation of INSL5 B
      chain and selective intramolecular A6-11 disulfide formation as a first step in
      sequential disulfide assembly.

PMID- 29466618
TI  - Exaggerated blood pressure variability is associated with memory impairment in
      very elderly patients.
AB  - We investigated the association between working memory (WM) impairment and blood
      pressure variability (BPV) in very elderly patients. Japanese outpatients >=80
      years who engaged in normal activities of daily living were the study cohort. WM
      function was evaluated by a simple visual WM test consisting of 3 figures. We
      considered the number of figures recalled by the patient his/her test score. We
      defined the patients with a score of 0 or 1 as those with WM impairment and those
      with scores of 2 or 3 as those without. To investigate the relative risk of WM
      impairment, we evaluated each patient's 24 hour ambulatory systolic blood
      pressure (SBP) and its weighted standard deviation (SDSBP ), office SBP, and the
      visit-to-visit SDSBP during the 1 year period from the patient's enrollment. A
      total of 66 patients (mean 84 +/- 3.6 years) showed WM impairment, and 431
      patients (mean 83 +/- 3.1 years) showed no WM impairment. There were no
      significant differences in 24 hour ambulatory SBP or office SBP between these two
      groups. However, the WM impairment patients showed significantly higher weighted
      SDSBP and visit-to-visit SDSBP values compared to the no-impairment group even
      after adjusting for age. Among these >=80-year-old patients, those with the
      highest quartile of both weighted SDSBP (>=21.4 mm Hg) and visit-to-visit SDSBP
      (>=14.5 mm Hg) showed the highest relative risk (odds ratio 3.52, 95% confidence
      interval 1.42-8.72) for WM impairment. Exaggerated blood pressure variability
      parameters were significantly associated with working memory impairment in very
      elderly individuals.

PMID- 29466611
TI  - Roles of UVA radiation and DNA damage responses in melanoma pathogenesis.
AB  - The growing incidence of melanoma is a serious public health issue that merits a
      thorough understanding of potential causative risk factors, which includes
      exposure to ultraviolet radiation (UVR). Though UVR has been classified as a
      complete carcinogen and has long been recognized for its ability to damage
      genomic DNA through both direct and indirect means, the precise mechanisms by
      which the UVA and UVB components of UVR contribute to the pathogenesis of
      melanoma have not been clearly defined. In this review, we therefore highlight
      recent studies that have addressed roles for UVA radiation in the generation of
      DNA damage and in modulating the subsequent cellular responses to DNA damage in
      melanocytes, which are the cell type that gives rise to melanoma. Recent research
      suggests that UVA not only contributes to the direct formation of DNA lesions but
      also impairs the removal of UV photoproducts from genomic DNA through oxidation
      and damage to DNA repair proteins. Moreover, the melanocyte microenvironment
      within the epidermis of the skin is also expected to impact melanomagenesis, and
      we therefore discuss several paracrine signaling pathways that have been shown to
      impact the DNA damage response in UV-irradiated melanocytes. Lastly, we examine
      how alterations to the immune microenvironment by UVA-associated DNA damage
      responses may contribute to melanoma development. Thus, there appear to be
      multiple avenues by which UVA may elevate the risk of melanoma. Protective
      strategies against excess exposure to UVA wavelengths of light therefore have the
      potential to decrease the incidence of melanoma. Environ. Mol. Mutagen. 59:438
      460, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29466619
TI  - Efficient synthesis of molecularly imprinted polymers with bio-recognition sites
      for the selective separation of bovine hemoglobin.
AB  - We developed a facile approach to the construction of bio-recognition sites in
      silica nanoparticles for efficient separation of bovine hemoglobin based on amino
      functionalized silica nanoparticles grafting by 3-aminopropyltriethoxylsilane
      providing hydrogen bonds with bovine hemoglobin through surface molecularly
      imprinting technology. The resulting amino-functionalized silica surface
      molecularly imprinted polymers were characterized using scanning electron
      microscope, transmission electronic microscopy, Fourier transform infrared
      spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis.
      Results showed that the as-synthesized imprinted polymers exhibited spherical
      morphology and favorable thermal stability. The binding adsorption experiments
      showed that the imprinted polymers can reach equilibrium within 1 h. The Langmuir
      isotherm and pseudo-second-order kinetic model fitted the adsorption data well.
      Meanwhile, the imprinted polymers possessed a maximum binding capacity up to 90.3
      mg/g and highly selectivity for the recognition of bovine hemoglobin. Moreover,
      such high binding capacity and selectivity retained after eight cycles,
      indicating the good stability and reusability of the imprinted polymers. Finally,
      successful application in the selective recognition of bovine hemoglobin from a
      real bovine blood sample indicated that the imprinted polymers displayed great
      potentials in efficient purification and separation of target proteins.

PMID- 29466620
TI  - Secretome Analysis of Hypoxia-Induced 3T3-L1 Adipocytes Uncovers Novel Proteins
      Potentially Involved in Obesity.
AB  - In the obese state, as adipose tissue expands, adipocytes become hypoxic and
      dysfunctional, leading to changes in the pattern of adipocyte-secreted proteins.
      To better understand the role of hypoxia in the mechanisms linked to obesity, we
      comparatively analyzed the secretome of murine differentiated 3T3-L1 adipocytes
      exposed to normoxia or hypoxia for 24 h. Proteins secreted into the culture media
      were precipitated by trichloroacetic acid and then digested with trypsin. The
      peptides were labeled with dimethyl labeling and analyzed by reversed phase
      nanoscale liquid chromatography coupled to a quadrupole Orbitrap mass
      spectrometer. From a total of 1508 identified proteins, 109 were differentially
      regulated, of which 108 were genuinely secreted. Factors significantly
      downregulated in hypoxic conditions included adiponectin, a known adipokine
      implicated in metabolic processes, as well as thrombospondin-1 and -2, and matrix
      metalloproteinase-11, all multifunctional proteins involved in extracellular
      matrix (ECM) homeostasis. Findings were validated by Western blot analysis.
      Expression studies of the relative genes were performed in parallel experiments
      in vitro, in differentiated 3T3-L1 adipocytes, and in vivo, in fat tissues from
      obese versus lean mice. Our observations are compatible with the concept that
      hypoxia may be an early trigger for both adipose cell dysfunction and ECM
      remodeling.

PMID- 29466621
TI  - Assessment of Arabidopsis thaliana CENH3 promoter in Brassica juncea for
      development of haploid inducer lines.
AB  - Centromeres are epigenetically specified by the centromeric histone H3 protein
      (CENH3). The timing and level of expression of CENH3 is tightly regulated to
      match the demands of the host cell. So far in plants, only CENH3 promoter of
      Arabidopsis thaliana (L.) Heynh. has been characterized. However, whether CENH3
      promoters retain their characteristic mode of regulation in other species remains
      to be established. In the present study, activity of AtCENH3 promoter was
      investigated using reporter gene assay in Brassica juncea (L.) Czem. A 1156 bp
      promoter fragment of AtCENH3 gene (At1g01370) including the first 111 nucleotides
      of the coding sequence was amplified and cloned into the pORE-R2 binary vector to
      ensure translation fusion with the uidA coding sequences. The Agrobacteriun
      tiunefaciens strain GV3101 harbouring the recombinant construct was used to
      transform B. juncea cv. RLM198 hypocotyl explants. Histochemical assay of To and
      T, transgenics showed GUS expression in shoot apical meristem, leaf, sepal,
      flower pedicel and root tip. Intense GUS expression was observed in meristematic
      tissues, particularly at shoot and root apices. However, mature leaves, flowers,
      pollen and ovules exhibited very low or no GUS expression. Our results showed
      that AtCENH3 promoter regulates cognate gene expression in Brassica juncea as it
      does in A. thaliana, and hence a suitable candidate for developing haploid
      inducer line in B. juncea.

PMID- 29466622
TI  - Isolation and characterization of Lepidoptera specific Bacillus thuringiensis
      strains predominantly from north-eastern states of India.
AB  - Both, the tobacco caterpillar Spodoptera litura (Fabricius) and the cotton
      bollworm Helicoverpa armigera (Hibner), are serious polyphagous pests causing
      considerable loss to crops. Indiscriminate use of chemical pesticides for
      controlling them has rather resulted in their resistance development. Microbial
      pesticides, Bacillus thuringiensis in particular, play an important role in pest
      management. Here, we isolated Bacillus thuringiensis-like bacteria from the soil
      samples primarily collected from North East region of India along with some
      states viz., Haryana, Punjab, Maharashtra, West Bengal and Uttarakhand and
      studied their toxicity against the above two insect pests at 10 gg/g along with
      standard strain B. thuringiensis subsp. kurstaki HD-I and at 1 pg/g
      Pseudomonasfluorescens based MVPII expressing CrylAc toxin and AUG-5. Isolates
      AUG-5 and GTG-7 proved toxic to more than 75% larvae on the 4h as well as 7h day
      of the treatment of the neonates of H. armigera. The AUG-5 isolate was also
      effective against S. litura. Ten effective isolates (AUG-5, GTG-4, GTG-7, GTG-9,
      GTG-42, GTG-64, GTG-70, GTG-3S, GTG-4S and GTG-6S) were characterized using
      biochemical and 16S rDNA analysis. Nearly, all the isolates tested positive for
      utilizing monosaccharides. All selected B. thuringiensis isolates showed
      resistance to ampicillin and co-trimoxazole except AUG-5 to- co-trimoxazole. AUG
      5 and GTG-7 were highly toxic to both insects, and possessed cryl, cry1A and cry2
      genes. These isolates AUG-5 and GTG-7 also contained high CrylAc (104.8 and 88.32
      ng/mg) and Cry2Ab (3792 and 1305.9 ng/mg), respectively in their spore-crystal
      complex. Both, AUG-5 and GTG-7 isolates, could be considered for further
      development as bioinsecticides. The present study has established the diversity
      and richness of B. thuringiensis-like isolates in soils collected from north
      eastern region of India.

PMID- 29466623
TI  - Differential antibrucella activity of bovine and murine macrophages.
AB  - Brucella abortus is. an intracellular pathogen affecting macrophages. Macrophages
      release some antibrucella componen such as lysozymes (LZ), reactive-oxygen
      species (ROS) and reactive nitrite intermediates (RNI) which prevent intracellul
      survival of Brucella. The present study compared the antibrucella activity of
      bovine and murine macrophages followir stimulation with B. abortus
      lipopolysaccharides. Our results revealed increased production of these
      antibrucella substanci in murine macrophages as compared to bovine macrophages.
      The differential production of these antibrucella componen explained the
      differential B. abortus killing ability of these species (bovine and mice) that
      was measured in terms intramacrophagic survival of Brucellae in murine and bovine
      macrophages.

PMID- 29466624
TI  - Effect of flavonoid rich fraction of Tephrosiapurpurea (Linn.) Pers. on
      complications associated with streptozotocin-induced type I diabetes mellitus.
AB  - Globally, diabetes is a serious health issue affecting one in 11 adults and
      consumes 12% of global health expenditure. Prevalence of dyslipidemia in diabetes
      is not uncommon since decades. Further, patients with type II diabetes have 2-4
      folds more risk for cardiovascular disease (CVD). Plants with antioxidant
      potential are known to have beneficial effects in diabetes and its complications:
      Natural compounds, flavonoids particularly, ameliorate hyperglycemia as well as
      CVD. Here, we evaluated common wasteland weed Tephrosia purpurea, used
      traditionally as folk medicine to treat many disorders including diabetes. We
      studied the effect of 8-wk treatment of flavonoid-rich fraction of T. purpurea
      (FFTp) (40 mg/kg/day/p.o.) on various biochemical, cardiovascular and lenticular
      parameters on streptozotocin (STZ) (45 mg/kg, i.v.) induced type I diabetic rats.
      STZ administration produced significant hyperglycemia, dyslipidemia, and altered
      cardiac biomarkers like lactate dehydrogenase, creatinine kinase and reduced
      antioxidants in lenticular tissues of rats. Treatment with FFTp significantly
      prevented STZ-induced hyperglycemia, dyslipidemia as well as cardiovascular
      markers. We observed decreased rate of pressure development (+dp/dt) and decay (
      dp/dt) in STZ diabetic hearts which was prevented by FFTp. Further, the soluble
      protein levels and the antioxidants were also elevated in the diabetic rats by
      the treatment. In conclusion, our data suggest that FFTp produces beneficial
      effects on diabetes induced cardiovascular complications and cataract. Such
      beneficial actions may be attributed to the antioxidant property of flavonoids,
      quercetin or rutin, present in T. purpurea.

PMID- 29466625
TI  - Antioxidant activity of Wattakaka volubilis (Linn. f.) leaf extract in carbon
      tetrachioride induced mice.
AB  - Plants are natural source of antioxidants which ameliorate a variety of diseases.
      In this study, we determined the in vitro and in vivo antioxidant activity of
      methanolic, polyphenolic and sapogenin mixture leaf extracts of Wattakaka
      volubilis (Linn.f.) Stapf, an ayurvedic medicinal plant. The in vitro antioxidant
      activity was tested spectrophotometrically by measuring ferric reducing power,
      DPPH and hydroxyl radical scavenging activity. Whereas the in vivo antioxidant
      activity was determined by estimation of enzymes catalase, superoxide dismutase
      (SOD), peroxidase and lipid peroxidation. In vitro study results showed that the
      tested extracts were capable of reducing ferric ion and scavenging free radical
      as well as hydroxyl radical. Treatment of mice with single dose of CCd4 resulted
      in decreased level of catalase, superoxide dismutase (SOD) and peroxidase, hut
      with 3-fold increase in lipid peroxidation. However, pretreatment of mice with
      methanolic and polyphenolic sample extracts caused prevention of catalase, and
      peroxidase when compared with control, where as lipid peroxidation was brought
      back to normal. NOS activity was also found significantly decreased.

PMID- 29466626
TI  - Validation of PCR based detection system for aflatoxin producing molds.
AB  - Aflatoxins are polyketide secondary metabolites that are produced by certain
      fungal species in the Aspergillus section Flavi, particularly Aspergillus flavus
      and Aspergillus parasiticus which contaminate human food as well as animal feed.
      These are among the most carcinogenic substances known. Due to the toxic and
      carcinogenic properties of aflatoxins, there is a need to develop reliable
      methods to detect the presence of aflatoxigenic Aspergilli in contaminated food
      and feed. Not all Aspergillus strains are able to produce aflatoxins. It requires
      a detection methodology which can specifically distinguish between the aflatoxin
      producing and nonproducing strains of Aspergillus. Present communication reports
      validation of a PCR based detection system based on three genes viz., nor-1, apa
      2 and omt-1 involved in aflatoxin biosynthesis, that can specifically distinguish
      the two aflatoxin producing species viz. Aspergillus flavus ,and Aspergillus
      parasiticus from non-producers i.e., A. niger, A. fumigates and A. oryzae.

PMID- 29466627
TI  - A rapid and efficient protocol for in vitro multiplication of genetically uniform
      Stevia rebaudiana (Bertoni).
AB  - Stevia rebaudiana (Bertoni), commonly called candy leaf or sweet leaf, endemic to
      South America, is an important medicinal plant. As a source of low calorie
      natural sweetener 'stevoside', it is used in obesity, diabetes, treatment of
      heartburn and tooth decay, and also serves as a food supplement. Large scale
      commercial propagation of S. rebaudiana demands a suitable protocol. Here, we
      propose an improved protocol for in vitro multiplication of S. rebaudiana from
      nodal explants. In this protocol, the effect of laboratory grade urea on multiple
      shoot induction from nodal explants was studied. The nodal explants were
      initially cultured on Murashige and Skoog (MS) basal media for 2 weeks which
      facilitated the axillary bud break. Further, culturing of these explants on MS
      medium fortified with 6 benzyl amninopurine (BAP) (2 mg/L) and Naphthalene acetic
      acid (NAA) (1 mg/L) with and .without urea (5 mg/L) for a period of 40 days
      revealed maximum shoot production of 44.56 from a single nodal explant in media
      supplemented with urea as compared to 22.44 without urea. The differences in the
      number of shoots produced were significant and these shoots readily rooted in MS
      media with NAA (4 mg/L). Primary and secondary hardening was successful in these
      plants. There were no visible morphological abnormalities observed in the
      micropropagated plantlets. Genetic analysis from random samples also revealed
      that these plants are genetically uniform. The advantage of the present protocol
      is that the complete process of multiple shoot induction, rooting and hardening
      could be completed within a period of 6 months as compared to the existing
      protocols.

PMID- 29466628
TI  - Influence of light intensity, temperature and CO2 concentration on growth and
      lipids in green algae and cyanobacteria.
AB  - Effects of the environmental variables such as light intensity (Vmol photons m-2
      S-1), temperature (*C) and CO2 concentration (ppm) on chlorophyll, total soluble
      proteins and lipids were studied in selected microalgal strains from
      Chlorophyceae (Chlamydomonas sp., Scenedesmus sp., Chlorella sp., Kirchneriella
      sp.) and cyanobacteria (Nostoc sp.1, Anabaena sp., Nostoc sp. 2, Cylindrospermum
      sp.). Cultures were grown under controlled conditions at the National Phytotron
      Facility, Indian Agricultural Research Institute (IARI), New Delhi. Our results
      showed that chlorophyll concentration enhanced with increased C02. Chlorella
      exhibited the highest chlorophyll at 850 ppm CO2 and 28*C; for Chlamydomonas it
      was at 78 MUmol photons m-2 S-1 light intensity. In Cylindrospernum, total
      soluble proteins decreased with enhanced C02, and were highest at 18*C. In
      Anabaena, a light intensity of 65 MUmol photons m-2 S-1 was best for maximum
      total soluble proteins. In Chlorella, CO2 @ 850 ppm was most suited for maximum
      lipid accumulation. In Kirchneriella, increase in temperature, from 18*C up to
      370C, increased total lipids; the highest was at 28'C. In Chlamydomonas, the
      light intensity of 78 MUmol photons m-2 S-1 was optimum for lipid accumulation
      and the maximum total lipids was 30.8 (% dry wt.).

PMID- 29466629
TI  - Diel variation in the catch of the shrimp Farfantepenaeus duorarum (Decapoda,
      Penaeidae) and length-weight relationship, in a nursery area of the Terminos
      Lagoon, Mexico.
AB  - The pink shrimp, Farfantepenaeus duorarum is an important commercial species in
      the Gulf of Mexico, which supports significant commercial fisheries near Dry
      Tortugas, in Southern Florida and in Campeche Sound, Southern Gulf of Mexico.
      There is information about the nictemeral behavior of the pink shrimp related to
      sunset, what is crucial to more accurate estimation of shrimp population biomass,
      and to assess the potential of this resource and its proper management. To
      contribute to the knowledge and the population dynamics of the species, shrimp
      surveys were conducted in a nursery area near "El Cayo" in the Northeastern part
      of Terminos Lagoon, Mexico during October 2010. Three sampling sites with
      substrate covered by submerged vegetation were chosen; two set of samples were
      collected at each site, one in the morning and the other just after sunset. Three
      trawls were performed per sampling site using a small otter trawl. A total of 1
      418 shrimp (between 5.5 to 28.8 mm Carapace Length (CL)) were collected during
      the study; 1 416 F. duorarum and only two individuals of Litopenaeus setiferus.
      Shrimps CL and Total Length (TL) were measured in mm and individuals were
      weighted to the nearest 0.01 g. In general, shrimp biomass and density were
      significantly higher in all sites during dusk (biomass = 46.36 g.100 m-2, n = 1
      344), than daylight samples (biomass = 2.78 g.100 m-2, n = 72). The One-way ANOVA
      and the Tukey test performed to evaluate variability in CL found significant
      differences between sites (CL = 14.12 mm, 12.46 mm and 15.13 mm, for site 1, 2
      and 3 respectively, F = 64.92, P < 0.001) which might be related to the substrate
      type. The length-weight relationships reflected positive allometric growth for
      juveniles but isometric for subadults and two nonlinear power functions were
      estimated (W = 0.0004CL3.157 for juveniles, and W = 0.0009CL2.902 for subadults).
      The results of the analysis of covariance (ANCOVA) test indicated that the Total
      Length - Carapace Length (TL-CL) relationships were significantly different
      between juveniles and subadults, and two linear equations (TL = 2.615 + 4.476CL
      and TL = 8.931 + 4.062CL for juveniles and subadults respectively) were fitted.
      It is important that population assessment takes into account the day or night
      period as a bias factor when sampling the abundance of the juveniles of F.
      duorarum in this important nursery ground of the Campeche Sound.

PMID- 29466630
TI  - [Spawning aggregations of Tylosurus pacificus (Beloniformes: Belonidae) and their
      fishery in Utria Park, Colombian Pacific].
AB  - Some species of marine fish have complex relationships with coastal ecosystems
      during their reproductive periods, as the needle fish Tylosurus pacificus that
      forms spawning aggregations in gravel beaches in Utria Park. We described fishery
      and some aspects of the reproductive biology of T. pacificus and proposed some
      strategies to mitigate the impact of this event and associated ecological
      processes. Fisheries monitoring were conducted between April 2008 and February
      2009 in the Utria National Park, Colombian Pacific. Catch volumes, length
      structure, sex ratio and fecundity (n= 84) were analyzed. The total length ranged
      among 60.5 and 104 cm with a mean and standard deviation of 85.35 +/- 9.09 cm.
      The average fertility of oocytes per gonad was 189 685.56, with a mode of 8 mm
      diameter and an asynchronous gonadal development. This species spawns
      collectively on the beach when the tide reaches the highest level during full and
      new moon, usually in the evening. Fishermen of a near town take advantage of the
      spawning aggregation of this species. The reproduction study of T. pacificus and
      ecological processes associated with their spawning, should be expanded to give
      adequate use, and ensure the sustainability of their fishery over the long term.

PMID- 29466631
TI  - Distribution of the deep-sea genus Bathypterois (Pisces: Ipnopidae) in the
      Eastern Central Pacific.
AB  - The genus Bathypterois (tripod fish) comprises 19 species of deep-sea fishes
      distributed worldwide. The biology and distribution of the species of this genus
      are relatively poorly known throughout the Eastern Central Pacific (ECP). This
      work aims to update the geographic and bathymetric distribution of species of
      Bathypterois throughout the ECP. To describe the influence of depth, temperature
      and dissolved oxygen concentrations (DO) on latitudinal and depth distribution of
      members of the genus throughout the Mexican Pacific, 51 specimens of B. atricolor
      (12 trawls) and 112 of B. ventralis (18 trawls), collected during TALUD project,
      were analyzed. Bathypterois atricolor had broader environmental niches (depth:
      0.47, temperature: 0.46, DO: 0.39), and inhabits deeper and colder sites
      (Electivity positives: > 1 000 m, < 3.2  degrees C, 1.0-1.62 mL/L) than B.
      ventralis, which had narrow environmental niches (depth: 0.34, temperature: 0.32,
      DO: 0.28), with high affinity to warmer sites and lower DO concentrations
      (Electivity positives: 778-1 400 m, 3.3-5.8  degrees C, < 1.0 mL/L). Both species
      used different environmental strata (niche overlap; depth: 0.34, temperature:
      0.32, DO: 0.28). The adaptation of B. atricolor to live in a broad range of DO
      concentrations explains its almost circumglobal distribution, while B. ventralis
      lives almost permanently in the Oxygen Minimum Zone (< 0.05 mL/L), so the DO
      could be a limiting factor, reducing its potential geographic and bathymetric
      distributions. None of these species had been previously recorded in the central
      Gulf of California, and B. ventralis had not been recorded along the West coast
      of Baja California. This study confirms that both species have a continuous
      distribution within the ECP, our new records extended the known northernmost
      range for B. atricolor by 886 km (from 22 degrees 46' N to 30 degrees 45' N) and
      for B. ventralis by 645 km (from 21 degrees 18' N to 27 degrees 07' N).

PMID- 29466632
TI  - The influence of habitat structure on fish assemblages in Amazonian streams of
      Machado river basin.
AB  - Igarapes are Amazonian streams that are extremely susceptible to environmental
      changes. Due to the rapidly occurring riparian land use changes, and the several
      impacts these may have on fish assemblages, it is highly valuable to describe and
      understand the current relationships between these assemblages and the local
      environmental conditions, especially in barely know areas. In this research, we
      studied the taxonomic composition and fish assemblage attributes variation in
      three streams with different riparian conservation conditions: forest,
      intermediate and pasture. Samplings were performed every two months from October
      2011 to September 2012, in three 1st order streams in the Machado River Basin,
      Rondonia. Fish were collected using trawls (seine net with a mesh size of 2 mm)
      and dip nets (2 mm mesh) along the entire stretch; the obtained samples were
      preserved and identified per site type. A total of 2 141 fish specimens belonging
      to 59 species, 17 families and five orders were recorded. Unlike the intermediate
      and pasture streams, the forest stream showed a high richness and low abundance.
      The forested stream exhibited the highest diversity and evenness value, and had
      low dominance, unlike the other streams. The variance partitioning and partial
      Redundancy Analysis (pRDA) indicated that assemblage composition was
      significantly explained by the environmental variables such as: depth, water
      velocity, pteridophytes and grasses, but not by spatial predictors. The non
      metric multidimensional scaling (NMDS) analysis showed that intermediate and
      pasture streams separated from the forested stream. We concluded that both, the
      stream environmental variables and fish assemblage attributes were influenced by
      the different conservation status and land cover. Given the influence of regional
      processes, which have a pervasive role in local fish assemblages, land use at the
      watershed scale is important, especially to explain the higher richness and
      diversity found in forested streams.

PMID- 29466633
TI  - [Distribution and abundance of the lionfish Pterois volitans (Scorpaeniformes:
      Scorpaenidae) and associated native species in Parque Marino Cayos de San Felipe,
      Cuba].
AB  - The first lionfish sighting at the National Park "Cayos de San Felipe" was in
      2009 and could be a threat to its marine ecosystem diversity and their capacity
      to generate services. To analyze the incidence of the lionfish invasion in the
      area, an annual sampling was conducted between 2013 and 2015. Lionfish abundance
      and size was investigated on mangroves through visual census on ten transects of
      30x2 m/station, and on coral reefs (15 and 25 m deep) with stereo video on six
      transects of 50x2 m/station. Additionally, incidence of potential native
      competitors and predators on coral reefs were also estimated. Over the three
      years, the average density of lionfish varied between 0.0-1.3 indiv./100 m2 per
      sample stations and it was not significantly different among habitats (mangroves
      with 0.6 indiv./100 m2, reefs at 15 m - 0.4 indiv./100 m2 and reef at 25 m with
      0.3 indiv./100 m2). Lionfish's density was equal to or lower than competitors'
      density, and was equal to or higher than predator's density in both depths. While
      lionfish density on mangroves and on reefs at 25 m remained temporally stable, it
      decreased on reefs at 15 m. Temporary increase in the competitor's density was
      observed and the predator's density did not change during the monitored time.
      Lionfish size varied between 5 and 39 cm; the average fish size from mangroves
      (12.6 cm) was consistently lower than from reefs (25.2 cm) and showed no
      variations among years. Lionfish size in reefs was higher than competitor's size
      and lower than that of predator. Results showed that in the park: 1) mangroves
      represent lionfish nursery areas; 2) incidence of reef lionfish was not as high
      as in other areas of Cuba and the Caribbean; and 3) lionfish abundance in reefs
      tended to decrease over the years, without the intervention of extractive
      activities or high abundance of large size native groupers. In this sense,
      recommendations are made to continue monitoring and to investigate lionfish
      effects and factors that are regulating its incidence in the park.

PMID- 29466634
TI  - Some intertidal and shallow water polychaetes of the Caribbean coast of Costa
      Rica.
AB  - The polychaete fauna of the Caribbean coast of Costa Rica has been inadequately
      characterized with only nine species previously reported. Collections of
      polychaetes from intertidal coralline rocks and several shallow sub-tidal sites
      on the Caribbean coast of Costa Rica have been examined and 68 species were
      identified. Of these, 66 are new records for Costa Rica.

PMID- 29466635
TI  - [Viability and germination of Hechtia perotensis (Bromeliaceae) seed].
AB  - Endemic populations of Hechtia perotensis have been described in Puebla and
      Veracruz, Mexico. Good quality seed collections can be used in conservation,
      research and ecological restoration. To evaluate seed quality of wild and endemic
      species, some compounds are used as effective promoters of germination, such as
      potassium nitrate (KNO3) and gibberellic acid (AG3), because they increase seed
      germination capacity and reduce latency. The triphenyl tetrazolium chloride
      (tetrazolium) test correlates seed viability because it is based on the activity
      of dehydrogenases in live tissues that catalyze mitochondrial respiration. The
      objective of this study was to obtain information on size and weight of capsules
      and seeds and seed germination and viability of H. perotensis, collected in
      Veracruz in the year 2012 and 2015. The hypotheses were 1) that seed germination
      and viability are independent of the year of collection, 2) that there is a
      tetrazolium concentration that can identify seed viability better than others,
      and 3) that pretreatment with KNO3 or AG3 improves seed germination. Seed
      germination was assessed using a completely randomized design with three
      treatments (control and the germination promoters 0.2 % KNO3 and 500 mg/L AG3),
      four treatments for the viability test (control, 0.2, 0.5 and 1.0 % of
      tetrazolium) and six replicates for each treatment. A total of one hundred seeds
      for germination experiments, and 25 seeds for the viability test were used. The
      results between and within years were analyzed with ANOVA and multiple comparison
      with the Tukey test. The proportion of non-germinated seeds was quantified along
      with the number of normal and abnormal seedlings, seeds with viable embryo, seeds
      without embryo, and seeds with low or no viability. On average, for the 2012
      collected sample, 36 % had viable embryos, 7 % had low viability, 24 % were not
      viable and 33 % had no embryo. This result was significantly different from the
      2015 sample, for which 87 % of seed showed viable embryos, 10 % had low
      viability, 0 % was not viable and 3 % had no embryo. Seed germination was also
      significantly different between years (22 and 92 %) Pregerminative treatments did
      not improve germination. Seed germination and viability of H. perotensis
      significantly varied between years of seed collection.

PMID- 29466636
TI  - [Spatial and temporal abundance and distribution of Stomolophus meleagris
      (Rhizostomae: Stomolophidae) in a lagoon system southern Gulf of Mexico].
AB  - The scyphomedusae feed mainly on microscopic crustaceans, eggs and fish larvae,
      molluscs and some other jellyfishes. The distribution and abundance of the
      scyphomedusae has an economic and ecological impact as they are predators that
      have an influence on the population dynamics of other fisheries. This
      investigation took place in the lagoon system 'Arrastradero-Redonda', Tabasco,
      from September 2013 to August 2014, with the purpose to provide information on
      the distribution, and spatial and temporal abundance of Stomolophus meleagris;
      along with its relation to environmental parameters. A total of 10 stations were
      defined and biological samples were taken on a monthly basis during this annual
      cycle. For this purpose, three pulls with a beach seine monofilament (20m long by
      3m height, mesh opening 1.5 cm, 5 to 10 minutes) per station were made within a 1
      km2 area. Information obtained was used to calculate the fishing efficiency
      analysis (CPUE con org./Evaluated Area Unit) and to determine the relationship
      with the environmental parameters. Our results showed that the abundance in the
      stations 1 to 3 was from 7 to 19 org./km2 from April to August 2014; less
      organisms were observed in stations 6 to 10 (an average of 1 org./km2) from
      October 2013 to March 2014. The multiple correlation steps analysis indicated
      that there is a strong association between the CPUE and some environmental
      investigated variables, and a 70.9 % variability of the data was observed. The
      salinity resulted the most important variable because it determined a 64.3 % of
      variation; it was followed by the temperature with a 3.6 %; meanwhile, dissolved
      oxygen explained only the 2.9 %, this was mainly because within the area there
      are several geological, oceanographic and biological factors that favor the
      distribution of this species due to seawater contribution through the Tupilco
      bar. With the provided data with this investigation we were able to determine the
      fishery potential of this resource for Tabasco state. However, additional
      research is required to allow an extended quantification of this resource, to
      determine the commercial exploitation areas, and drive studies about reproductive
      and feeding habits, that may provide the necessary information to establish plans
      for sustainable use.

PMID- 29466637
TI  - [Reproduction of Centropomus undecimalis and C. ensiferus (Perciformes:
      Centropomidae) in a tropical coastal lagoon].
AB  - Snooks C. undecimalis and C. ensiferus are important fishery resources in their
      distribution area. In Venezuela they are caught by artisanal fisheries along the
      entire coast. However, studies on their biology that would help establish fishing
      regulations are scarce. To study reproduction aspects of these species, we
      analyzed 1 325 individuals of C. undecimalis and 2 025 of C. ensiferus caught by
      artisanal fishing in the Laguna de Tacarigua in Northern Venezuela, from July
      2009 to September 2010. Total length, total weight, sex and stage of gonadal
      development were recorded. The sex ratio varied throughout the year: there was a
      significant difference in favor of C. undecimalis males (1.5:1), and C. ensiferus
      females (1:3.3). Differences were also evident in the sexual proportion at each
      size group. For both species, males dominated in the lower size ranges while
      females dominated in the larger size ranges. These results suggested sequential
      hermaphroditism (protrandry) in both species. Size at sexual maturity (Lm50) for
      C. undecimalis was ?= 73.6 and ?= 59.3 cm, and ?= 26 and ?= 21.5 cm for C.
      ensiferus. C. ensiferus reproduced throughout the year with two periods of higher
      intensity (August to September and February to April). Although we found very few
      mature individuals for C. undecimalis, February showed an important reproduction
      peak. Growth differences were found between males and females of C. undecimalis:
      positive allometry for females (P= 0.0022*L3.353) and negative allometry for
      males (P= 0.0108*L2.945). Both males and females of C. ensiferus showed a
      positive allometric relationship (P= 0.0049*L3.235). Lack of fishing regulations
      and controls, evidenced in this study by significant volumes of immature
      individuals in the catches, and the particular reproductive biology of these
      species, strongly indicates the need to establish regulations to ensure their
      responsible use. We recommend establishing a closed season during the first
      quarter of the year and minimum catch sizes for both species.

PMID- 29466638
TI  - [Economic potential of ornamental fish catching under federal protection in
      Mexico.].
AB  - Ornamental fisheries are economically viable activities in developing countries
      due to the fact that aquaria have become a worldwide hobby. In Mexico, the
      fishery has been conducted since the 1980s, especially in the Baja California
      Peninsula, but nevertheless, there are no adequate records of commercial
      production, or about the economic gain due to the exploitation of the resource.
      The objective of this paper was to calculate the maximum allowable catch for the
      five ornamental fishes included in the NOM-059-SEMARNAT (protected by federal
      mandate), and the net monetary gain that the resource might generate. Censuses
      (N=1 610) were conducted in 21 reef sites of the Mexican Pacific and Gulf of
      California in order to estimate population density of each taxon; also, natural
      mortality rate (M) was calculated from maximum size (Linfinity), individual
      growth rate (k) and temperature (C), and the total allowable catch was estimated
      on the basis of M. Finally, considering the prices of the species paid to
      fishermen at the beach, an estimation of the economic value of a single fishing
      season for an area of 220 hectares (representative of the catch area assigned in
      average to a cooperative in Mexico) was produced.  The results indicated that the
      areas with the best economic potential were Encantadas Islands, Los Angeles Bay,
      and San Lorenzo Archipelago (all in the state of Baja California). Outside of the
      gulf (where no legal ornamental fisheries exist) the potentially more rentable
      locations were Marietas Islands (Jalisco), and the Revillagigedo Islands.
      Aquarium fisheries may be a viable activity in several of the analyzed areas of
      the country, however, the potential gain that harvest represents is not enough to
      fully sustain an organized group that would perform it; for that reason the
      ornamental fishery should be seen as an alternative commercial activity. Finally,
      to guarantee this activity to be a rentable and sustainable fishery, we
      recommended that, the existing rules defined by the Mexican federal government
      should be applied to control the catch quotas.

PMID- 29466639
TI  - [Nesting ecology of Crocodylus acutus (Reptilia: Crocodylidae) in Bahia Portete,
      La Guajira, Colombia].
AB  - C. acutus is cataloged in critical danger in Colombia. We studied its population
      at Bahia Portete, in order to survey the nesting activities and to obtain
      valuable information for a conservation management program. This study was
      undertaken with the participation of the Wayuu community using the Agreement
      Conservation Model, and took place during July 2007, August 2008, June and August
      2009, and March to August 2010 and 2011. Sampling surveys were made by the use of
      transects along the coast, in order to find nests. For each nesting area found,
      we recorded the nests biometrics, eggs and hatchlings, fertility of the eggs and
      reproductive events. We explored a total of 55.12 km, and determined four nesting
      areas. Colonial nesting and the environmental variables were factors that
      affected the hatchling success. From the total of nests found, 37 % were oriented
      towards North, and 48 % were built next to Stenocereus griseus. Juyi island
      substrate was mostly constituted by sand (71.9 %, 71.44 %). The average number of
      eggs by nest was 28.42 +/- 6.63, the largest egg diameter was 71.84 +/- 3.54 mm,
      the average nest weight was 81.54 +/- 9.99 g, and the hatchlings presented an
      average length of 25.47 +/- 1.16 cm. For this specific site in Colombia, the
      reproductive period begins in March and ends in August. The few areas of nesting
      and the 95 % fertility suggest the performance of a conservation management
      program for this species at Bahia Portete.

PMID- 29466640
TI  - Trypanosoma evansi (Kinetoplastida: Trypanosomatidae) in capybaras (Hydrochoerus
      hydrochaeris, Rodentia: Hydrochoeridae): prevalence, effect and sexual selection.
AB  - Parasites play a crucial role in the ecology of animals. They also appear to be
      important in mechanisms underlying sexual selection processes. In this article we
      study the prevalence, effect and potential role in sexual selection of the
      protozoon Trypanosoma evansi in capybaras, Hydrochoerus hydrochaeris. We
      collected our samples from the annual capybara cull of a ranch in Venezuela,
      using the volume of the snout scent gland as an indicator of dominance; the
      residuals of body weight as indicators of condition; and the residuals of the
      spleen mass as indicators of immune function. Overall prevalence was 30.9% (N=97)
      with no difference between males and females and no relation between infection
      with T. evansi and condition. However, we found that infected animals had larger
      spleens (residuals), indicating an immunological cost of the infection. Further,
      males with larger snout scent glands (more dominant) were less likely to be
      infected than males with smaller glands (less dominant) suggesting that by
      choosing males with a large gland, females may be using the gland as an indicator
      of health, which is consistent with the "good genes" view of sexual selection.

PMID- 29466641
TI  - [Basic biological parameters for Pseudocurimata lineopunctata (Characiformes,
      Curimatidae) conservation in the Anchicaya River of the Cauca Valley, Colombia].
AB  - Pseudocurimata lineopunctata represents an important nutritional source for local
      human communities in Colombia and Ecuador. Although the yearly catch of this fish
      is low (590 kg/year), there are no restrictions on minimum size, and this species
      is categorized as vulnerable with moderate extinction risk by the Regional
      Autonomous Corporation of the Cauca Valley (Colombia). To support conservation
      programs, biological data of the target species are required. Therefore, the aims
      of this study were to describe the sex ratio, distribution, size to weight ratio,
      macroscopic stages of reproductive maturity, fecundity, and size at first sexual
      maturity for P. lineopunctata. For this, fish samples were captured with nets
      over nine months (February-October) in 2007. The total length (Lt) of the
      captured fish ranged between 10.7 and 16.5 cm, with total weight (Pt) between
      25.0 and 67.5 g. Females represented 52.6 % of the sample group while males
      represented 47.4 %, and differences in sex ratio were observed in relation to
      fish size. For all sampled months, the fish captured showed an advanced maturity
      state. Based on analyses of the gonadosomatic index (IGS), gonadic index (IG),
      and Fulton's condition factor (K), and two spawning peaks were determined, one in
      June-July, and the other in September-October. The size at first sexual maturity
      was 9.2 cm for females and 10.1 cm for males. Absolute fecundity was estimated as
      3 598 oocytes/g?. It is necessary to carry out additional investigations on the
      reproduction of this species, to support future repopulation programs.

PMID- 29466642
TI  - Reproductive cycle of the endemic and threatened fish Puntius shalynius
      (Cypriniformes: Cyprinidae) in Meghalaya, India.
AB  - Puntius shalynius is a highly endemic freshwater minor carp that is economically
      important and isthreatened because of its ornamental value. The present
      investigation evaluated this barb gonadal maturation,based on morphology and
      spawning of this species in the Umiam river, Meghalaya, India. The population
      ofthis indigenous fish has declined due to its fragmented distribution and
      exploitation as an ornamental fish. Thereproductive cycle of P. shalynius was
      studied for the first time. A total of 609 fish samples were randomly
      collectedfrom the river for a period of two years during January 2010 and
      December 2011. Five maturity phases(rest, primary growth, secondary growth, ripe
      and spent) were observed on the basis of ovarian and testicularmacroscopic
      evaluation throughout the annual cycle. Peak spawning activity was observed in
      the month of June/July and it coincided with the start of the monsoon season. The
      study showed that the fish spawns once in a yearwith single spawning peak and
      that the species is a low fecund fish. It is important to conserve this species
      forits unique ecological value and urgent management policies should promote its
      sustainable utilization.

PMID- 29466643
TI  - Divergent predation environment between two sister species of livebearing fishes
      (Cyprinodontiformes: Poeciliidae) predicts boldness, activity, and exploration
      behavior.
AB  - Predators can influence a variety of prey traits, including behavior. Traits such
      as boldness, activity rate, and tendency to explore can all be shaped by
      predation risk. Our study examines the effects of predation on these behaviors by
      considering a natural system in which two sister species of livebearing fishes,
      Brachyrhaphis roseni and B. terrabensis, experience divergent predation
      environments. In February of 2013, we collected fish in the Rio Chiriqui Nuevo
      drainage, Chiriqui, Panama, and conducted behavioral assays. Using open-field
      behavioral assays, we evaluated both juveniles and adults, and males and females,
      to determine if there were differences in behavior between ontogenetic stages or
      between sexes. We assessed boldness as 'time to emerge' from a shelter into a
      novel environment, and subsequently measured activity and exploration within that
      novel environment. We predicted that B. roseni (a species that co-occurs with
      predators) would be more bold, more active, and more prone to explore, than B.
      terrabensis (a species that does not co-occur with predators). In total, we
      tested 17 juveniles, 21 adult males, and 20 adult females of B. roseni, and 19
      juveniles, 19 adult males, and 18 adult females of B. terrabensis. We collected
      all animals from streams in Chiriqui, Panama in February 2013, and tested them
      following a short acclimation period to laboratory conditions. As predicted, we
      found that predation environment was associated with several differences in
      behavior. Both adult and juvenile B. roseni were more active and more prone to
      explore than B. terrabensis. However, we found no differences in boldness in
      either adults or juveniles. We also found a significant interaction between 'sex'
      and 'species' as predictors of boldness and exploration, indicating that
      predation environment can affect behaviors of males and females differently in
      each species. Our work demonstrates the importance of considering sex and life
      history stage when evaluating the evolution of behavior.

PMID- 29466644
TI  - [Ants' higher taxa as surrogates of species richness in a chronosequence of
      fallows, old-grown forests and agroforestry systems in the Eastern Amazon,
      Brazil].
AB  - Deforestation in Amazon forests is one of the main causes for biodiversity loss
      worldwide. Ants are key into the ecosystem because act like engineers; hence, the
      loss of ants' biodiversity may be a guide to measure the loss of essential
      functions into the ecosystems. The aim of this study was to evaluate soil ant's
      richness and to estimate whether higher taxa levels (Subfamily and Genus) can be
      used as surrogates of species richness in different vegetation types (fallows,
      old-growth forests and agroforestry systems) in Eastern Amazon. The samples were
      taken in 65 areas in the Maranhao and Para States in the period 2011-2014. The
      sampling scheme followed the procedure of Tropical Soil Biology and Fertility
      (TSBF). Initially, the vegetation types were characterized according to their age
      and estimated species richness. Linear and exponential functions were applied to
      evaluate if higher taxa can be used as surrogates and correlated with the Pearson
      coefficient. In total, 180 species distributed in 60 genera were identified. The
      results showed that ant species richness was higher in intermediate fallows (88)
      and old secondary forest (76), and was lower in agroforestry systems (38) and
      mature riparian forest (35). The genus level was the best surrogate to estimate
      the ant's species richness across the different vegetation types, and explained
      72-97 % (P < 0.001) of the total species variability. The results confirmed that
      the genus level is an excellent surrogate to estimate the ant's species richness
      in the region and that both fallows and agroforestry systems may contribute in
      the conservation of Eastern Amazon ant community.

PMID- 29466645
TI  - Oocyte distribution within and between ovary lobes is largely homogeneous in
      Lachnolaimus maximus (Perciformes: Labridae).
AB  - Studies of fish reproductive biology often involve quantitative estimates based
      on histological sections of the ovaries. Prior characterization of gonad oocyte
      distribution patterns in females is fundamental to these studies. Heterogeneous
      distribution requires a standardized sampling protocol to prevent bias in data
      such as fecundity estimations. In contrast, homogeneous distribution allows
      sampling of any portion of the gonads with no risk of bias. A preliminary study
      was done of gonad oocyte distribution mode in a hogfish Lachnolaimus maximus
      population in the southern Gulf of Mexico. A total of 23 sexually-active females
      were selected and classified by reproductive stage. Six histological sections
      were taken from the anterior, middle and posterior regions of the left and right
      ovary lobes of each individual. Digital image processing (AxioVision and Image
      ProPlus programs) was used to estimate oocyte density per unit area in different
      development stages. Contingency tables were used to analyze oocyte distribution
      frequencies between the regions of each lobe and between the lobes of each ovary.
      This was supported with a Pearson's chi2 test for goodness-of-fit and a
      replicated G test to confirm distribution heterogeneity. Oocyte type distribution
      was homogeneous in almost all the females regardless of ovary region or lobe.
      This was particularly the case for females in the actively spawning reproductive
      subphase. Females in this subphase are normally used to estimate batch fecundity
      in fish species such as L. maximus, which have asynchronous oocyte development
      and batch spawning. However, heterogeneity was present in tertiary vitellogenesis
      oocytes in the right lobe of females in the spawning capable reproductive phase.
      In these cases, it is preferable to take histological sections from any region of
      the left ovary lobe to ensure unbiased estimation of fecundity and adequate
      characterization of this species' sexual cycle.

PMID- 29466646
TI  - Estimation of genetic variation in closely related cycad species in Ceratozamia
      (Zamiaceae: Cycadales) using RAPDs markers.
AB  - The Ceratozamia norstogii complex from Southern Mexico is made up of four closely
      related taxa and occurs in similar habitats (Quercus forest). All have linear
      lanceolate leaflets with great similarity between them, especially in juvenile
      stages, but differentiate with age. There has been debate regarding delimitation
      of species due to character loss in herbarium specimens. The aim of this study
      was to determine the genetic variation, and to measure genetic similarity between
      the four taxa. We studied populations in Cintalapa (Chiapas) for C. alvarezii and
      C. norstogii; the Sierra Atravesada (Oaxaca) for C. chimalapensis, and Villa
      Flores (Chiapas) for C. mirandae. One population for each taxon was sampled (only
      one population is known for C. alvarezii) 11-15 randomly chosen adult individuals
      were sampled. Twenty-eight primers were tested of which five were polymorphic
      using the RAPD'S technique. The data were analyzed using Bayesian methods.
      Results revealed low genetic diversity, and a differentiation was found between
      species, suggesting a recent divergence. A previous morphological and anatomical
      study on the complex has found the taxa to be distinct. However, the results of
      this study have shown that the C. norstogii species complex is in a divergence
      process, probably through genetic drift and founder effects.

PMID- 29466647
TI  - [Leaf-litter breakdown as a tool to assess the functional integrity of high
      Andean streams of Southern Ecuador].
AB  - The ecological condition of tropical Andean rivers are threatened by many human
      activities including changes in land use and cover in watersheds. Current
      protocols diagnose the structural condition of streams but not their function. In
      this study we proposed an assessment tool using the leaf-litter breakdown as a
      measure of the functional condition and health of high Andean streams in Southern
      Ecuador, including methodology and threshold values adapted to local conditions.
      We selected 15 streams in three micro-basins (Mazan, Llaviuco and Matadero)
      within or in the vicinity of Cajas National Park where we deployed litterbags for
      15, 28 and 64 days. We used two types of mesh (coarse and fine) for the
      litterbags in order to separate the contribution of macro-invertebrates and
      microorganisms in the decomposition process and also tested two different leaf
      substrates: Alder (Alnus acuminata) and Miconia (Miconia bracteolata). In each
      collection period we determined physical and chemical parameters, applied the
      riparian quality index (QBR-And) and river habitat index (IHF). Decomposition
      rates (-k) were determined from the time period at which approximately 50 % ash
      free mass would have been lost. We used Ktotal and the ratio of the rate of
      decomposition between coarse and fine mesh (Kg/Kf) to define the functional
      condition thresholds. To test the metrics sensitivity we used graphical methods,
      one-way ANOVA and discriminative efficiency (ED). The analysis of watershed land
      use and cover showed a gradient of intervention: Matadero >= Llaviuco > Mazan.
      The composition of the environmental variables of Mazan streams were different
      with respect to Llaviuco and Matadero, whose values were similar to each other.
      The QBR-And index showed a significant gradient from very low levels in Matadero
      (27.5), moderately high values in Llaviuco (66.5) to high values in Mazan (87).
      Alder leaf-litter breakdown rates were significantly faster in Mazan than in
      Matadero and Llaviuco streams, while breakdown rates of Miconia were not
      significantly different among watersheds. The Kg/Kf ratio was significantly
      higher in Mazan compared to Llaviuco and Matadero, which did not differ. We
      consider the Kg/Kf metric sensitive enough to discriminate impacts in the studied
      areas. Our results support the use of the leaf-litter breakdown as an appropriate
      tool to assess functional ecological condition, complementing the structural
      assessments of these Andean rivers.

PMID- 29466648
TI  - Reproductive pattern of the large fruit-eating bat, Artibeus amplus (Chiroptera:
      Phyllostomidae) in the Venezuelan Andes.
AB  - Bimodal polyestry is the most common reproductive pattern in tropical bats, and
      it consists in producing one offspring per female twice a year. Reproductive
      patterns are closely related to rainfall regimes, frequently occurring twice a
      year in tropical regions. The goal of our study was to determine the reproductive
      pattern of the large fruit-eating bat, Artibeus amplus Handley, 1987 in a cave in
      the Venezuelan Andes inhabited by a large, stable colony. Thus, in this study we
      describe for the first time this important biological aspect of this unknown
      Neotropical bat species through the examination of external reproductive
      characteristics of males (inguinal or scrotal testes) and females (pregnant,
      lactating, post-lactating), based on 211 individuals (120 males and 91 females)
      captured between September 2008 and August 2009, in Cueva del Parque Las
      Escaleras, Estado Tachira, Venezuela. During this period of monthly sampling for
      a full year, most males displayed large scrotal testes, averaging 10 mm maximum
      length. The examination of females indicated that although pregnancy was first
      observed in November 2008, it reached a maximum during January and February 2009.
      Although adult males with scrotal testes throughout the year could imply that
      females have more than one pregnancy, our results suggested a seasonally
      monoestrous reproductive pattern for A. amplus. This study represents the first
      report of reproductive pattern for this poorly-known Neotropical frugivorous
      species. The observed monoestrous reproductive pattern supports the existence of
      synchronization between precipitation and reproduction. This synchronization has
      been frequently observed in most species of fruit bats. In this study, Artibeus
      amplus presumably adjust the parturition to anticipate the rainy season, as a
      strategy that allows maintenance of offspring during high availability of fruits.

PMID- 29466649
TI  - Preclinical efficacy against toxic activities of medically relevant Bothrops sp.
      (Serpentes: Viperidae) snake venoms by a polyspecific antivenom produced in
      Mexico.
AB  - The assessment of the preclinical neutralizing ability of antivenoms in Latin
      America is necessary to determine their scope of efficacy. This study was aimed
      at analyzing the neutralizing efficacy of a polyspecific bothropic-crotalic
      antivenom manufactured by BIRMEX in Mexico against lethal, hemorrhagic,
      defibrinogenating and in vitro coagulant activities of the venoms of Bothrops
      jararaca (Brazil), B. atrox (Peru and Colombia), B. diporus (Argentina), B.
      mattogrossensis (Bolivia), and B. asper (Costa Rica). Standard laboratory tests
      to determine these activities were used. In agreement with previous studies with
      bothropic antivenoms in Latin America, a pattern of cross-neutralization of
      heterologous venoms was observed. However, the antivenom had low neutralizing
      potency against defibrinogenating effect of the venoms of B. atrox (Colombia) and
      B. asper (Costa Rica), and failed to neutralize the in vitro coagulant activity
      of the venom of B. asper (Costa Rica) at the highest antivenom/venom ratio
      tested. It is concluded that, with the exception of coagulant and
      defibrinogenating activities of B. asper (Costa Rica) venom, this antivenom
      neutralizes toxic effects of various Bothrops sp venoms. Future studies are
      necessary to assess the efficacy of this antivenom against other viperid venoms.

PMID- 29466650
TI  - [Comparison between Phyllophaga (Coleoptera: Melolonthidae) assemblages in
      Western Cuba].
AB  - The Cuban archipelago has 79 Phyllophaga species with a 98.6 % of endemism, which
      makes the group ecologically and economically important, as some species are
      classified as crop pests. The aim of this study was to determine the relationship
      between the composition and structure of the Phyllophaga assemblages with their
      habitat type, considering both plant structure and level of human habitat
      disturbance. A total of 17 locations were sampled in Western Cuba during the
      rainy seasons of the period from 2011 to 2015; these differed in habitat types
      (forests and agroecosystems). Samplings followed standard methods and were made
      once with a light trap screen in each locality. A total of 1153 individuals of 24
      Phyllophaga species were collected. The total abundance of collected individuals
      varied between 10 and 306, and species richness between two and nine species. The
      most abundant species was Phyllophaga dissimilis (Chevrolat) which also had the
      highest frequency of occurrence. Generally, less anthropized sites reflected
      richer and equitative communities; although these characteristics appeared in two
      sites that showed intermediate degree of disturbance. The non-metric
      multidimensional scaling showed that the most similar samples were those of the
      very anthropized sites; this similarity was given mainly by the abundance of
      Phyllophaga dissimilis, P. insualepinorum and P. puberula. Besides, the
      geographical distance was not related to the similarity of these assemblages.

PMID- 29466651
TI  - Reproductive biology of Sodhiana iranica (Brachyura: Gecarcinucidae) from
      Southern Iran.
AB  - Freshwater crab, Sodhiana iranica, is an endemic gecarcinucid crab that has been
      recently reported from Southern Iran. This research examined some reproductive
      aspects of S. iranica from Eelood freshwater spring, Southern Iran. Crabs were
      haphazardly sampled from April 2012 to April 2013, on a bimonthly basis.
      Measurements of Gonado-Somatic Index (GSI), Hepato-Somatic Index (HSI), oocyte
      diameter, and other aspects such as carapace width (CW) and total body weight
      (TW) were made in the captured specimens. Results showed a single seasonal
      reproductive cycle. Maturation and spawning occurred from December 2012 to April
      2013 during the study period. The peaks of HSI were observed in April 2012 and
      February 2013. The oocyte diameter showed its most significant increase between
      August 2012 and February 2013. Considering the single seasonal breeding of S.
      iranica, a correct management, during the reproductive cycle, is necessary to
      support a healthy stock of this crab.

PMID- 29466652
TI  - Galapagos macroalgae: A review of the state of ecological knowledge.
AB  - Previous work has highlighted the critical role of macroalgal productivity and
      dynamics in supporting and structuring marine food webs. Spatio-temporal
      variability in macroalgae can alter coastal ecosystems, a relationship
      particularly visible along upwelling-influenced coastlines. As a result of its
      equatorial location and nutrient rich, upwelling-influenced waters, the Galapagos
      Archipelago in the East Pacific, hosts a productive and biodiverse marine
      ecosystem. Reports and collections of macroalgae date back to the Beagle voyage,
      and since then, more than three hundred species have been reported. However,
      their ecology and functional role in the ecosystem is not well understood.
      According to various disparate and in part anecdotal sources of information,
      abundant and diverse communities exist in the Western regions of the archipelago,
      the North is essentially barren, and in the central/South abundance and
      distribution is variable and less well defined. Both oceanographic conditions and
      herbivore influence have been theorized to cause this pattern. Extensive changes
      in macroalgal productivity and community composition have occurred during strong
      ENSO events, and subsequent declines in marine iguana (an endemic and iconic
      grazer) populations have been linked to these changes. Iguanas are only one
      species of a diverse and abundant group of marine grazers in the system,
      highlighting the potentially important role of macroalgal productivity in the
      marine food web. This review represents a first compilation and discussion of the
      available literature and presents topics for future research.

PMID- 29466653
TI  - [Soil seed bank formation during early revegetation of areas affected by mining
      in a tropical rain forest of Choco, Colombia].
AB  - Mining is one of the main economic activities in many tropical regions and is the
      cause of devastation of large areas of natural tropical forests. The knowledge of
      the regenerative potential of mining disturbed areas provides valuable
      information for their ecological restoration. The aim of this study was to
      evaluate the effect of age of abandonment of mines and their distance from the
      adjacent forest, on the formation of soil seed bank in abandoned mines in the San
      Juan, Choco, Colombia. To do this, we determined the abundance and species
      composition of the soil seed bank, and the dynamics of seed rain in mines of
      different cessation period of mining activity (6 and 15 years), and at different
      distances from the adjacent forest matrix (50 and 100 m). Seed rain was composed
      by five species of plants with anemocorous dispersion, and was more abundant in
      the mine of 6 years than in the mine of 15 years. There were no significant
      differences in the number of seeds collected at 50 m and 100 m from the adjacent
      forest. The soil seed bank was represented by eight species: two with anemocorous
      dispersion (common among the seed rain species) and the rest with zoochorous
      dispersion. The abundance of seeds in the soil did not vary with the age of the
      mine, but was higher at close distances to the forest edge than far away. During
      the early revegetation, the formation of the soil seed bank in the mines seems to
      be related to their proximity to other disturbed areas, rather than their
      proximity to the adjacent forest or the cessation activity period of mines.
      Therefore, the establishment of artificial perches or the maintenance of isolated
      trees in the abandoned mines could favour the arrival of bird-dispersed seeds at
      mines. However, since the soil seed bank can be significantly affected by the
      high rainfall in the study area, more studies are needed to evaluate management
      actions to encourage soil seed bank formation in mines of high-rainfall
      environments in the Choco region.

PMID- 29466654
TI  - [Genotoxic evaluation of Rio Grande (Antioquia, Colombia) water using
      micronucleus frequency in erythrocytes of Brycon henni (Characiformes:
      Characidae)].
AB  - The permanent monoculture of bananas and plantains farming in the middle of Rio
      Grande (Turbo - Antioquia) requires the application of a variety of pesticides.
      Inappropriate banana production practices in this region, have often led to
      waterbody pollution by agrochemicals from leachate and runoff processes.
      Currently, fish are the most common vertebrates used as bioindicators of water
      quality, because they are very sensitive to the presence of contaminants. Our
      main goal with this study was to compare the frequency of micronucleated
      erythrocytes (MNE) in peripheral blood specimens of fish Brycon henni, from two
      locations (polluted and unpolluted) in the Rio Grande. We evaluated the frequency
      of MNE in peripheral blood samples of fish B. henni from each location during two
      rainy seasons in 2010 and two dry seasons in 2011. Blood samples were collected,
      fixed for 24 h, and then were stained with Giemsa. Among results, we found that
      the median frequency of MNE was higher in the polluted site by agrochemical
      discharges (0.15+/-0.18), than in the unimpacted site (0.06+/-0.08). Furthermore,
      the frequency of MNE in B. henni during the dry season was highly significant for
      both locations. The results of this study indicated that the analysis of MNE in
      B. henni could be recommended as a suitable method for in situ detection of
      environmental genotoxins.

PMID- 29466655
TI  - 2018 Congress Podium Abstracts
AB  - Each abstract has been indexed according to first author. Abstracts appear as
      they were submitted and have not undergone editing or the Oncology Nursing
      Forum's review process. Only abstracts that will be presented appear here. For
      Congress scheduling information, visit congress.ons.org or check the Congress
      guide. Data published in abstracts presented at the ONS 43rd Annual Congress are
      embargoed until the conclusion of the presentation. Coverage and/or distribution
      of an abstract, poster, or any of its supplemental material to or by the news
      media, any commercial entity, or individuals, including the authors of said
      abstract, is strictly prohibited until the embargo is lifted. Promotion of
      general topics and speakers is encouraged within these guidelines.

PMID- 29466656
TI  - 2018 Congress Poster Abstracts
AB  - Each abstract has been indexed according to the first author. Abstracts appear as
      they were submitted and have not undergone editing or the Oncology Nursing
      Forum's review process. Only abstracts that will be presented appear here. Poster
      numbers are subject to change. For updated poster numbers, visit congress.ons.org
      or check the Congress guide. Data published in abstracts presented at the ONS
      43rd Annual Congress are embargoed until the conclusion of the presentation.
      Coverage and/or distribution of an abstract, poster, or any of its supplemental
      material to or by the news media, any commercial entity, or individuals,
      including the authors of said abstract, is strictly prohibited until the embargo
      is lifted. Promotion of general topics and speakers is encouraged within these
      guidelines.

PMID- 29466657
TI  - Chemiluminescent Biosensors for Detection of Second Messenger Cyclic di-GMP.
AB  - Bacteria colonize highly diverse and complex environments, from gastrointestinal
      tracts to soil and plant surfaces. This colonization process is controlled in
      part by the intracellular signal cyclic di-GMP, which regulates bacterial
      motility and biofilm formation. To interrogate cyclic di-GMP signaling networks,
      a variety of fluorescent biosensors for live cell imaging of cyclic di-GMP have
      been developed. However, the need for external illumination precludes the use of
      these tools for imaging bacteria in their natural environments, including in deep
      tissues of whole organisms and in samples that are highly autofluorescent or
      photosensitive. The need for genetic encoding also complicates the analysis of
      clinical isolates and environmental samples. Toward expanding the study of
      bacterial signaling to these systems, we have developed the first
      chemiluminescent biosensors for cyclic di-GMP. The biosensor design combines the
      complementation of split luciferase (CSL) and bioluminescence resonance energy
      transfer (BRET) approaches. Furthermore, we developed a lysate-based assay for
      biosensor activity that enabled reliable high-throughput screening of a
      phylogenetic library of 92 biosensor variants. The screen identified biosensors
      with very large signal changes (~40- and 90-fold) as well as biosensors with high
      affinities for cyclic di-GMP ( KD < 50 nM). These chemiluminescent biosensors
      then were applied to measure cyclic di-GMP levels in E. coli. The cellular
      experiments revealed an unexpected challenge for chemiluminescent imaging in Gram
      negative bacteria but showed promising application in lysates. Taken together,
      this work establishes the first chemiluminescent biosensors for studying cyclic
      di-GMP signaling and provides a foundation for using these biosensors in more
      complex systems.

PMID- 29466658
TI  - Variability in Disinfection Resistance between Currently Circulating Enterovirus
      B Serotypes and Strains.
AB  - The susceptibility of waterborne viruses to disinfection is known to vary between
      viruses and even between closely related strains, yet the extent of this
      variation is not known. Here, different enteroviruses (six strains of
      coxsackievirus B5, two strains of coxsackievirus B4 and one strain of
      coxackievirus B1) were isolated from wastewater and inactivated by UV254,
      sunlight, free chlorine (FC), chlorine dioxide (ClO2), and heat. Inactivation
      kinetics of these isolates were compared with those of laboratory enterovirus
      strains (CVB5 Faulkner and echovirus 11 Gregory) and MS2 bacteriophage. FC
      exhibited the greatest (10-fold) variability in inactivation kinetics between
      different strains, whereas inactivation by UV254 differed only subtly. The
      variability in inactivation kinetics was greater between serotypes than it was
      among the seven strains of the CVB5 serotype. MS2 was a conservative surrogate of
      enterovirus inactivation by UV254, sunlight, or heat but frequently
      underestimated the disinfection requirements for FC and ClO2. Similarly,
      laboratory strains did not always reflect the inactivation behavior of the
      environmental isolates. Overall, there was considerable variability in
      inactivation kinetics among and within enteroviruses serotypes, as well as
      between laboratory and environmental isolates. We therefore recommend that future
      disinfection studies include a variety of serotypes and environmental isolates.

PMID- 29466659
TI  - Soil Bacteria Override Speciation Effects on Zinc Phytotoxicity in Zinc
      Contaminated Soils.
AB  - The effects of zinc (Zn) speciation on plant growth in Zn-contaminated soil in
      the presence of bacteria are unknown but are critical to our understanding of
      metal biodynamics in the rhizosphere where bacteria are abundant. A 6-week pot
      experiment investigated the effects of two plant growth promoting bacteria
      (PGPB), Rhizobium leguminosarum and Pseudomonas brassicacearum, on Zn
      accumulation and speciation in Brassica juncea grown in soil amended with 600 mg
      kg-1 elemental Zn as three Zn species: soluble ZnSO4 and nanoparticles of ZnO and
      ZnS. Measures of plant growth were higher across all Zn treatments inoculated
      with PGPB compared to uninoculated controls, but Zn species effects were not
      significant. Transmission electron microscopy identified dense particles in the
      epidermis and intracellular spaces in roots, suggesting Zn uptake in both
      dissolved and particulate forms. X-ray absorption near-edge structure (XANES)
      analysis of roots revealed differences in Zn speciation between treatments.
      Uninoculated plants exposed to ZnSO4 contained Zn predominantly in the form of Zn
      phytate (35%) and Zn polygalacturonate (30%), whereas Zn cysteine (57%) and Zn
      polygalacturonate (37%) dominated in roots exposed to ZnO nanoparticles.
      Inoculation with PGPB increased (>50%) the proportion of Zn cysteine under all Zn
      treatments, suggesting Zn coordination with cysteine as the predominant mechanism
      of Zn toxicity reduction by PGPB. Using this approach, we show, for the first
      time, that although speciation is important, the presence of rhizospheric
      bacteria completely overrides speciation effects such that most of the Zn in
      plant tissue exists as complexes other than the original form.

PMID- 29466661
TI  - Heterogeneity in Nitrogen Sources Enhances Productivity and Nutrient Use
      Efficiency in Algal Polycultures.
AB  - Algae hold much promise as a potential feedstock for biofuels and other products,
      but scaling up biomass production remains challenging. We hypothesized that
      multispecies assemblages, or polycultures, could improve crop yield when grown in
      media with mixed nitrogen sources, as found in wastewater. We grew mono- and poly
      cultures of algae in four distinct growth media that differed in the form (i.e.,
      nitrate, ammonium, urea, plus a mixture of all three) but not the concentration
      of nitrogen. We found that mean biomass productivity was positively correlated
      with algal species richness, and that this relationship was strongest in mixed
      nitrogen media (on average 88% greater biomass production in 5-species
      polycultures than in monocultures in mixed nitrogen treatment). We also found
      that the relationship between nutrient use efficiency and species richness was
      positive across nitrogen treatments, but greatest in mixed nitrogen media. While
      polycultures outperformed the most productive monoculture only 0-14% of the time
      in this experiment, they outperformed the average monoculture 26-52% of the time.
      Our results suggest that algal polycultures have the potential to be highly
      productive, and can be effective in recycling nutrients and treating wastewater,
      offering a sustainable and cost-effective solution for biofuel production.

PMID- 29466660
TI  - A Versatile Approach to Noncanonical, Dynamic Covalent Single- and Multi-Loop
      Peptide Macrocycles for Enhancing Antimicrobial Activity.
AB  - Peptide oligomers offer versatile scaffolds for the formation of potent
      antimicrobial agents due to their high sequence versatility, inherent
      biocompatibility, and chemical tunability. Though many methods exist for the
      formation of peptide-based macrocycles (MCs), increasingly pervasive in
      commercial antimicrobial therapeutics, the introduction of multiple looped
      structures into a single peptide oligomer remains a significant challenge.
      Herein, we report the utilization of dynamic hydrazone condensation for the
      versatile formation of single-, double-, and triple-loop peptide MCs using simple
      dialdehyde or dihydrazide small-molecule cross-linkers, as confirmed by MALDI-TOF
      MS, HPLC, and SDS-PAGE. Furthermore, incorporation of aldehyde-containing side
      chains onto peptides synthesized from hydrazide C-terminal resins resulted in
      tunable peptide MC assemblies formed directly upon resin cleavage post solid
      phase peptide synthesis. Both of these types of dynamic covalent assemblies
      produced significant enhancements to overall antimicrobial properties when
      introduced into a known antimicrobial peptide, buforin II, when compared to the
      original unassembled sequence.

PMID- 29466662
TI  - Tracing the Uptake, Transport, and Fate of Mercury in Sawgrass ( Cladium
      jamaicense) in the Florida Everglades Using a Multi-isotope Technique.
AB  - The role of macrophytes in the biogeochemical cycle of mercury (Hg) in the
      Florida Everglades is poorly understood. Stable isotope tracer techniques were
      employed to investigate Hg uptake by sawgrass ( Cladium jamaicense) from soil and
      atmospheric pathways and the fate of Hg after absorption. Our results suggest
      that soil spiked 201Hg2+ was rapidly taken up by roots and transported to
      aboveground parts. The spiked 201Hg that was transported to the aboveground parts
      was trapped; no release of the spiked 201Hg from the leaf to the air was
      detected. Atmospheric 199Hg0 exposure experiments revealed that the majority of
      the previously deposited 199Hg0 taken into the leaf was fixed, with a very
      limited proportion (1.6%) available for re-emission to the atmosphere. The
      percentage of 199Hg0 fixed in the leaf will help reduce the model uncertainty in
      estimating the Hg0 exchange over the air-vegetation surface. We propose that
      sawgrass needs to be viewed as an important sink for atmospheric Hg0 in the
      regional Hg mass balance; this would have important implications for the critical
      loads of Hg to the Everglades. The multi-isotope tracer technique could be an
      effective tool to identify the role of plants in biogeochemical cycling of Hg in
      other ecosystems.

PMID- 29466663
TI  - Cis-to- Trans Isomerization of Azobenzene Derivatives Studied with Transition
      Path Sampling and Quantum Mechanical/Molecular Mechanical Molecular Dynamics.
AB  - Azobenzene-based molecular photoswitches are becoming increasingly important for
      the development of photoresponsive, functional soft-matter material systems. Upon
      illumination with light, fast interconversion between a more stable trans and a
      metastable cis configuration can be established resulting in pronounced changes
      in conformation, dipole moment or hydrophobicity. A rational design of functional
      photosensitive molecules with embedded azo moieties requires a thorough
      understanding of isomerization mechanisms and rates, especially the thermally
      activated relaxation. For small azo derivatives considered in the gas phase or
      simple solvents, Eyring's classical transition state theory (TST) approach yields
      useful predictions for trends in activation energies or corresponding half-life
      times of the cis isomer. However, TST or improved theories cannot easily be
      applied when the azo moiety is part of a larger molecular complex or embedded
      into a heterogeneous environment, where a multitude of possible reaction pathways
      may exist. In these cases, only the sampling of an ensemble of dynamic reactive
      trajectories (transition path sampling, TPS) with explicit models of the
      environment may reveal the nature of the processes involved. In the present work
      we show how a TPS approach can conveniently be implemented for the phenomenon of
      relaxation-isomerization of azobenzenes starting with the simple examples of pure
      azobenzene and a push-pull derivative immersed in a polar (DMSO) and apolar
      (toluene) solvent. The latter are represented explicitly at a molecular
      mechanical (MM) and the azo moiety at a quantum mechanical (QM) level. We
      demonstrate for the push-pull azobenzene that path sampling in combination with
      the chosen QM/MM scheme produces the expected change in isomerization pathway
      from inversion to rotation in going from a low to a high permittivity (explicit)
      solvent model. We discuss the potential of the simulation procedure presented for
      comparative calculation of reaction rates and an improved understanding of
      activated states.

PMID- 29466664
TI  - Fixed-Node, Importance-Sampling Diffusion Monte Carlo for Vibrational Structure
      with Accurate and Compact Trial States.
AB  - We present a new approach to importance sampling in diffusion Monte-Carlo (DMC)
      simulations of vibrational excited states whereby the trial wave functions for
      low-energy states are incorporated into the diffusion equations so as to enforce
      their orthogonality. For the model systems examined here, simple variational wave
      functions based on the vibrational self-consistent field (VSCF) and the simplest
      vibrational configuration interaction (VCI) are effective in importance sampling
      provided that internal coordinates used in the underlying one-particle functions
      have been variationally optimized. The resulting model yields results comparable
      in accuracy to the best unguided DMC calculations without requiring an a priori
      choice of coordinates to specify nodal hyperplanes.

PMID- 29466665
TI  - Detecting and Visualizing Reaction Intermediates of Anisotropic Nanoparticle
      Growth.
AB  - This paper describes a correlative approach to detect, visualize, and
      characterize intermediate species during a seedless, anisotropic nanoparticle
      synthesis. Changes in radical concentration as a function of time were correlated
      in situ to the optical properties and morphology of the particles. Depending on
      type and concentration of reaction precursors, either one or two increases in
      radical production occurred, corresponding to initial particle formation and
      increased branch length, respectively. Thus, changes in radical intensity can be
      considered as an indicator of nanoparticle structure and properties.

PMID- 29466666
TI  - Snapshots of the Catalytic Cycle of an O2, Pyridoxal Phosphate-Dependent
      Hydroxylase.
AB  - Enzymes that catalyze hydroxylation of unactivated carbons normally contain heme
      and nonheme iron cofactors. By contrast, how a pyridoxal phosphate (PLP)
      dependent enzyme could catalyze such a hydroxylation was unknown. Here, we
      investigate RohP, a PLP-dependent enzyme that converts l-arginine to ( S)-4
      hydroxy-2-ketoarginine. We determine that the RohP reaction consumes oxygen with
      stoichiometric release of H2O2. To understand this unusual chemistry, we obtain
      ~1.5 A resolution structures that capture intermediates along the catalytic
      cycle. Our data suggest that RohP carries out a four-electron oxidation and a
      stereospecific alkene hydration to give the ( S)-configured product. Together
      with our earlier studies on an O2, PLP-dependent l-arginine oxidase, our work
      suggests that there is a shared pathway leading to both oxidized and hydroxylated
      products from l-arginine.

PMID- 29466667
TI  - Boron Carbonyl Analogues of Hydrocarbons: An Infrared Photodissociation
      Spectroscopic Study of B3(CO) n+ ( n = 4-6).
AB  - The boron carbonyl cluster cations in the form of B3(CO) n+ ( n = 4-6) are
      produced and studied by infrared photodissociation spectroscopy in the carbonyl
      stretching frequency region in the gas phase. Their geometric structures are
      determined with the aid of density functional theory calculations. The B3(CO)4+
      cation is characterized to have a D2 d (OC)2B?B?B(CO)2 structure and 1A1
      electronic ground state with a linear boron skeleton. The B3(CO)5+ cation is
      determined to have a chain boron framework with C2 v symmetry. The B3(CO)6+
      cation is a weakly bound CO-tagged complex involving a B3(CO)5+ ion core. Bonding
      analysis reveals that B3(CO)4+ has a chemical bonding pattern similar to allene,
      while bonding in B3(CO)5+ is similar to that in allyl anion.

PMID- 29466668
TI  - Quantitative Analysis of Glucose Metabolic Cleavage in Glucose Transporters
      Overexpressed Cancer Cells by Target-Specific Fluorescent Gold Nanoclusters.
AB  - The glucose metabolism rate in cancer cells is a crucial piece of information for
      the cancer aggressiveness. A feasible method to monitor processes of oncogenic
      mutations has been demonstrated in this work. The fluorescent gold nanoclusters
      conjugated with glucose (glucose-AuNCs) were successfully synthesized as a cancer
      targeting probe for glucose transporters (Gluts) overexpressed by U-87 MG cancer
      cells, which can be observed under confocal microscopy. The structural and
      optical characterizations of fluorescent glucose-AuNCs were confirmed by
      transmission electron microscope (TEM) and Fourier transform infrared
      spectroscopy (FTIR). The MTT assay exhibited the high biocompatibility of water
      soluble glucose-AuNCs for further biomedical applications. The glucose metabolic
      cleavage of glucose-AuNCs by glycolytic enzymes from U-87 MG cancer cell was
      measured by fluorescence change of glucose-AuNCs. The fluorescence change based
      on the integrated area under fluorescence spectra ( A t) of glucose-AuNCs was
      plotted as a function of different reaction time ( t) with glycolytic enzymes.
      The fitted curve of A t versus t showed the first-order kinetics to explain the
      mechanism of glucose metabolic cleavage rate of glucose-AuNCs by glycolytic
      enzymes. The rate constant k could be utilized to determine the glucose
      metabolism rate of glucose-AuNCs for the quantitative analysis of cancer
      aggressiveness. Our work provides a practical application of target-specific
      glucose-AuNCs as a fluorescence probe to analyze the glucose metabolism in Gluts
      overexpressed cancer cells.

PMID- 29466669
TI  - A Model of Uranium Uptake by Plant Roots Allowing for Root-Induced Changes in the
      soil.
AB  - We develop a model with which to study the poorly understood mechanisms of
      uranium (U) uptake by plants. The model is based on equations for transport and
      reaction of U and acids and bases in the rhizosphere around cylindrical plant
      roots. It allows for the speciation of U with hydroxyl, carbonate, and organic
      ligands in the soil solution; the nature and kinetics of sorption reactions with
      the soil solid; and the effects of root-induced changes in rhizosphere pH. A
      sensitivity analysis showed the importance of soil sorption and speciation
      parameters as influenced by pH and CO2 pressure; and of root geometry and root
      induced acid-base changes linked to the form of nitrogen taken up by the root.
      The root absorbing coefficient for U, relating influx to the concentration of U
      species in solution at the root surface, was also important. Simplified empirical
      models of U uptake by different plant species and soil types need to account for
      these effects.

PMID- 29466670
TI  - Long noncoding RNA HOTAIR mediates the estrogen-induced metastasis of endometrial
      cancer cells via the miR-646/NPM1 axis.
AB  - LncRNA homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) has been
      confirmed to be involved in the tumorigenic progression of endometrial carcinoma
      (EC). However, the molecular mechanisms of HOTAIR in EC are not fully elucidated.
      The expression of HOTAIR and miR-646 in human EC tissues was determined by qRT
      PCR. The effect of miR-646 on EC cells was assessed by the cell viability,
      migration, and invasion using CCK-8 assays and transwell assays. RNA-binding
      protein immunoprecipitation assays and RNA pull-down assays were performed to
      explore the interaction between HOTAIR and miR-646. The regulation of miR-646 on
      nucleophosmin 1 (NPM1) was tested using luciferase reporter assays. MiR-646
      expression was significantly decreased both in human EC tissues ( n = 23) and
      cell lines (Ishikawa and HEC-1-A) compared with the control. Moreover, miR-646
      expression was negatively related to HOTAIR in human EC tissues ( n = 23). Our
      results also showed that miR-646 overexpression considerably attenuated the E2
      promoted viability, migration, and invasion of Ishikawa and HEC-1-A cells in
      vitro. In addition, HOTAIR was confirmed to regulate the viability, migration,
      and invasion of EC cells through negative regulating miR-646. More importantly,
      we also demonstrated that NPM1 was the target of miR-646, and HOTAIR promoted
      NPM1 expression through interacting with miR-646 in EC cells. Taken together, our
      findings presented that HOTAIR could regulate NPM1 via interacting with miR-646,
      thereby governing the viability, migration, and invasion of EC cells.

PMID- 29466671
TI  - Lipopolysaccharide stimulates BK channel activity in bladder umbrella cells.
AB  - Bladder urothelium plays an active role in response to bacterial infection. There
      is little known about the electrophysiological activity in urothelial cells in
      this process. We used a nonenzymatic method to isolate bladder urothelial tissue
      and to patch clamp umbrella cells in situ. A 200 pS conductance potassium (K+)
      channel was detected from female C57BL6 mice. Of 58 total patches, 17.2% patches
      displayed the 200 pS K+ conductance channel. This K+ conductance channel showed
      Ca2+ sensitivity and voltage dependence. Specific big-conductance potassium
      channel (BK) inhibitors (paxilline, iberiotoxin) blocked the 200 pS K+
      conductance channel activity. RT-PCR and immunoblot confirmed BK channel pore
      forming alpha-subunit (BK-alpha) mRNA and protein in urothelium.
      Immunohistochemistry also showed the BK-alpha located in urothelium. The above
      data provided evidence that the 200 pS K+ conductance channel was a BK channel.
      Lipopolysaccharide (LPS), a component of uropathogenic Escherichia coli, was used
      to investigate the role of BK channel in the pathogenesis of urinary tract
      infection. BK channel activity as NPo increased threefold within 30 min of
      exposure to LPS. mRNAs for LPS receptors (TLR4, CD14, MD-2) were expressed in the
      urothelium but not in lamina propria or detrusor. Blockade of the receptors by an
      antagonist (polymyxin B) abrogated LPS's effect on BK channel. The involvement of
      protein kinase A (PKA) on BK channel activity was demonstrated by applying PKA
      blockers (H89 and PKI). Both PKA inhibitors abolished the BK channel activity
      induced by LPS. In conclusion, BK channel was identified in bladder umbrella
      cells, and its activity was significantly increased by LPS.

PMID- 29466672
TI  - The long noncoding RNA SNHG1 promotes nucleus pulposus cell proliferation through
      regulating miR-326 and CCND1.
AB  - Aberrant nucleus pulposus cell proliferation is implicated in the development of
      intervertebral disk degeneration (IDD). Recent studies have suggested that long
      noncoding RNAs (lncRNAs) can modulate cell proliferation in several pathological
      conditions. Here, we indicate that expression of SNHG1 was upregulated in IDD
      tissues compared with control tissues and that higher SNHG1 expression was
      associated with disk degeneration grade. In addition, we show that ectopic
      expression of SNHG1 promoted nucleus pulposus (NP) cell proliferation and
      increased the PCNA and cyclin D1 expression in NP cells. Ectopic expression of
      SNHG1 inhibited miR-326 expression in nucleus pulposus cells and promoted CCND1
      expression, which is a direct target gene of SNHG1. Moreover, we demonstrate that
      expression of miR-326 was downregulated in IDD tissues compared with control
      tissues and that lower SNHG1 expression was associated with disk degeneration
      grade. Expression of miR-326 was negatively associated with SNHG1 expression in
      disk degeneration tissues. Overexpression of miR-326 inhibited NP cell growth and
      inhibited PCNA and cyclin D1 expression in NP cells. Furthermore, we show that
      overexpression of SNHG1 promoted nucleus pulposus cell proliferation through
      inhibiting miR-326 expression. These data shed novel light on the role of SNHG1
      in the pathogenesis of IDD.

PMID- 29466674
TI  - Expiratory Flow Limitation Assessment in Patients with Acute Respiratory Distress
      Syndrome. A Reappraisal.

PMID- 29466673
TI  - Advancing Quality Improvement with Regression Discontinuity Designs.

PMID- 29466675
TI  - Emerging drugs for alopecia areata: JAK inhibitors.
AB  - INTRODUCTION: Alopecia Areata is a common form of non-scarring hair loss that
      usually starts abruptly with a very high psychological impact. Due to the still
      not completely understood etiopathogenesis, at present there is no treatment that
      can induce a permanent remission and there is no drug approved for the treatment
      of this disorder. Areas covered: Leading existing treatment are briefly
      overviewed and then ongoing research on Janus Kinases Inhibitors is discussed,
      reviewing trials with oral and topical formulations so as new opportunities for
      other forms of alopecia, such as cicatricial alopecia. Expert opinion: JAK
      inhibitors represent a promise among alopecia treatments, but further studies are
      needed on long term safety. There is still no validated dosage for alopecia
      areata and the vehicles used for topical formulations seem not yet ideal in terms
      of skin penetration and reduced systemic absorption. Hopefully several studies
      are ongoing and we hope, in the near future, that JAK inhibitors will become part
      of the armamentarium to treat alopecia areata patients in terms of safety and
      costs.

PMID- 29466676
TI  - Establishing MALDI-TOF as Versatile Drug Discovery Readout to Dissect the PTP1B
      Enzymatic Reaction.
AB  - Label-free, mass spectrometric (MS) detection is an emerging technology in the
      field of drug discovery. Unbiased deciphering of enzymatic reactions is a
      proficient advantage over conventional label-based readouts suffering from
      compound interference and intricate generation of tailored signal mediators.
      Significant evolvements of matrix-assisted laser desorption/ionization time-of
      flight (MALDI-TOF) MS, as well as associated liquid handling instrumentation,
      triggered extensive efforts in the drug discovery community to integrate the
      comprehensive MS readout into the high-throughput screening (HTS) portfolio.
      Providing speed, sensitivity, and accuracy comparable to those of conventional,
      label-based readouts, combined with merits of MS-based technologies, such as
      label-free parallelized measurement of multiple physiological components,
      emphasizes the advantages of MALDI-TOF for HTS approaches. Here we describe the
      assay development for the identification of protein tyrosine phosphatase 1B
      (PTP1B) inhibitors. In the context of this precious drug target, MALDI-TOF was
      integrated into the HTS environment and cross-compared with the well-established
      AlphaScreen technology. We demonstrate robust and accurate IC50 determination
      with high accordance to data generated by AlphaScreen. Additionally, a tailored
      MALDI-TOF assay was developed to monitor compound-dependent, irreversible
      modification of the active cysteine of PTP1B. Overall, the presented data proves
      the promising perspective for the integration of MALDI-TOF into drug discovery
      campaigns.

PMID- 29466677
TI  - Analysis of Graft Length Change Patterns in Medial Patellofemoral Ligament
      Reconstruction via a Fluoroscopic Guidance Method.
AB  - BACKGROUND: A fluoroscopic guidance method for medial patellofemoral ligament
      (MPFL) reconstruction has been widely used to determine the anatomic femoral
      attachment site. PURPOSE: To examine the graft length change patterns in MPFL
      reconstruction with a fluoroscopic guidance method. STUDY DESIGN: Cross-sectional
      study; Level of evidence, 3. METHODS: Forty-four knees of 42 patients who
      underwent MPFL reconstruction for the treatment of recurrent patellar dislocation
      were examined prospectively. During surgery, suture anchors were inserted into
      the proximal one-third and center of the patella. A guide pin for the femoral
      tunnel was inserted into the position reported by Schottle et al based on the
      true lateral view of the knee under fluoroscopic control. Changes in graft length
      patterns of the proximal and center anchors were examined through 0 degrees  to
      120 degrees  of knee flexion. Favorable changes in length patterns were defined
      as meeting 2 of 3 criteria: (1) not long during flexion (<=3 mm between 30
      degrees  and 120 degrees  of flexion) and either (2) nearly isometric during
      flexion between 0 degrees  and 90 degrees  or (3) slightly long during maximum
      extension (<=3 mm). Other patterns were considered unfavorable. If the change in
      length pattern was unfavorable, then the pin for the femoral tunnel was moved to
      different positions until it was favorable. Knees were separated into the
      favorable group and the unfavorable group. Differences between the groups
      regarding radiographic parameters were assessed. Student t test or chi-square
      test was used for statistical analysis. RESULTS: Of the 44 knees, 31 (70.5%)
      showed favorable patterns. However, 13 knees (29.5%) showed unfavorable patterns;
      therefore, the position of the pin was changed. The mean +/- SD distance from the
      original position to the final position was 5.3 +/- 1.1 mm distal for 7 patients
      and 5.2 +/- 0.4 mm posterodistal for 6 patients. Technical errors, including a
      nontrue lateral view and the tip of the wire not being in the determined area,
      were found for 4 of 13 knees in the unfavorable group. There was no statistical
      difference in radiographic parameters between the groups. CONCLUSION: The graft
      length change pattern could be nonphysiologic at the position determined through
      the fluoroscopic guidance method; thus, caution may be necessary. The change in
      length pattern should be checked before graft fixation. If the length change
      pattern is unfavorable, then it is advisable to move it approximately 5 to 7 mm
      distally or posterodistally from the first position.

PMID- 29466678
TI  - Update in Asthma 2017.

PMID- 29466679
TI  - A Biomechanical Comparison of Fifth Metatarsal Jones Fracture Fixation Methods.
AB  - BACKGROUND: Fifth metatarsal base fractures of the metaphyseal-diaphyseal
      watershed junction (Jones fracture) are commonly treated with surgical fixation
      in athletes. Intramedullary screw fixation remains the most utilized construct,
      although plantar-lateral plating is an alternative. Purpose/Hypothesis: The
      purpose was to compare the mechanical strength of fracture fixation between an
      intramedullary screw and plantar-lateral plating. The hypothesis was that plantar
      lateral plate fixation would allow for more cycles and higher peak loads before
      failure, as well as less fracture gapping, than would an intramedullary screw in
      cadaveric foot specimens with simulated Jones fractures exposed to cantilever
      bending. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve pairs of male
      cadaver feet were separated into 2 groups (plate or screw) to conduct
      contralateral comparative testing of 2 devices with equally numbered right and
      left feet. For each fifth metatarsal, an osteotomy with a microsagittal saw was
      created to simulate a Jones fracture. The plate group underwent fixation with a
      3.0-mm 4-hole low-profile titanium plate placed plantar-laterally with 3 locking
      screws and 1 nonlocking screw. The screw group underwent fixation with a 40- or
      45-mm * 5.5-mm partially threaded solid titanium intramedullary screw. After
      fixation, the metatarsals were excised for biomechanical testing. Cyclic
      cantilever failure testing was conducted with a gradient-cycle method. Sinusoidal
      loading forces were applied, increasing by 5.0-pound-force increments per 10
      cycles, until each specimen experienced mechanical failure of implant or bone.
      Failure mode, number of cycles to failure, peak failure load, gap width at the
      last mutual prefailure loading, and video data were recorded. Paired 2-tailed t
      test (alpha = 0.05) was used to compare groups ( P < .05 set for significance).
      RESULTS: Failure mode in both groups occurred predominantly at the bone-implant
      interface. Plate fixation resulted in significantly higher mean +/- SD values for
      cycles to failure (63.9 +/- 27.0 vs 37.3 +/- 36.9, P = .01) and peak failure load
      (159.2 +/- 60.5 N vs 96.5 +/- 45.8 N, P = .01), with a significantly lower mean
      gap width (0.0 +/- 0.0 mm vs 3.2 +/- 2.4 mm, P < .01). CONCLUSION: As compared
      with intramedullary screw fixation, plantar-lateral plating allowed for greater
      cycles to failure and peak load before failure, as well as less gap width, when
      applied to cadaver foot specimens with simulated Jones fractures exposed to
      cantilever bending in a load frame. CLINICAL RELEVANCE: Early return to play
      among athletes before Jones fracture union is associated with increased risk of
      failure. This study introduces a plantar-lateral plating construct that performed
      more favorably than intramedullary screw fixation when applied to simulated Jones
      fractures in cadaveric foot specimens. Further clinical comparative studies are
      needed to assess the clinical use of this construct.

PMID- 29466681
TI  - Cookstove Trials and Tribulations: What Is Needed to Decrease the Burden of
      Household Air Pollution?

PMID- 29466680
TI  - Cytokine Responses to Rhinovirus and Development of Asthma, Allergic
      Sensitization, and Respiratory Infections during Childhood.
AB  - RATIONALE: Immunophenotypes of antiviral responses, and their relationship with
      asthma, allergy, and lower respiratory tract infections, are poorly understood.
      OBJECTIVES: We characterized multiple cytokine responses of peripheral blood
      mononuclear cells to rhinovirus stimulation, and their relationship with clinical
      outcomes. METHODS: In a population-based birth cohort, we measured 28 cytokines
      after stimulation with rhinovirus-16 in 307 children aged 11 years. We used
      machine learning to identify patterns of cytokine responses, and related these
      patterns to clinical outcomes, using longitudinal models. We also ascertained
      phytohemagglutinin-induced T-helper cell type 2 (Th2)-cytokine responses (PHA
      Th2). MEASUREMENTS AND MAIN RESULTS: We identified six clusters of children based
      on their rhinovirus-16 responses, which were differentiated by the expression of
      four cytokine/chemokine groups: interferon-related (IFN), proinflammatory
      (Inflam), Th2-chemokine (Th2-chem), and regulatory (Reg). Clusters differed in
      their clinical characteristics. Children with an IFNmodInflamhighestTh2
      chemhighestReghighest rhinovirus-16-induced pattern had a PHA-Th2low response,
      and a very low asthma risk (odds ratio [OR], 0.08; 95% confidence interval [CI],
      0.01-0.81; P = 0.03). Two clusters had a high risk of asthma and allergic
      sensitization, but with different trajectories from infancy to adolescence. The
      IFNlowestInflamhighTh2-chemlowRegmod cluster exhibited a PHA-Th2lowest response
      and was associated with early-onset asthma and sensitization, and the highest
      risk of asthma exacerbations (OR, 1.37; 95% CI, 1.07-1.76; P = 0.014) and lower
      respiratory tract infection hospitalizations (OR, 2.40; 95% CI, 1.26-4.58; P =
      0.008) throughout childhood. In contrast, the IFNhighestInflammodTh2
      chemmodReghigh cluster with a rhinovirus-16-cytokine pattern was characterized by
      a PHA-Th2highest response, and a low prevalence of asthma/sensitization in
      infancy that increased sharply to become the highest among all clusters by
      adolescence (but with a low risk of asthma exacerbations). CONCLUSIONS: Early
      onset troublesome asthma with early-life sensitization, later-onset milder
      allergic asthma, and disease protection are each associated with different
      patterns of rhinovirus-induced immune responses.

PMID- 29466682
TI  - No effect of acute normobaric hypoxia on plasma triglyceride levels in fasting
      healthy men.
AB  - Circulating fatty acids are a major systemic energy source in the fasting state
      as well as a determinant of hepatic triglycerides (TG)-rich very-low-density
      lipoprotein production. Upon acute hypoxia, sympathetic arousal induces adipose
      tissue lipolysis, resulting in an increase in circulating nonesterified fatty
      acids (NEFA). Animal studies suggest that TG clearance may also be strongly
      reduced under hypoxia, though this effect has been shown to be dependent on
      temperature. Whether the hypoxia-induced rise in blood fatty acid concentrations
      affects fasting TG levels in humans under thermoneutral conditions remains
      unknown. TG, NEFA, and glycerol levels were measured in fasted healthy young men
      (n = 10) exposed for 6 h to either normoxia (ambient air) or acute hypoxia
      (fraction of inspired oxygen = 0.12) in a randomized, crossover design.
      Participants were casually clothed and rested in front of a fan in an
      environmental chamber maintained at 28  degrees C during each trial. Under
      hypoxia, a significantly greater increase in NEFA occurred (condition * time
      interaction, p = 0.049) and glycerol levels tended to be higher (condition *
      time, p = 0.104), suggesting an increase in adipose tissue lipolysis. However,
      plasma TG levels did not change over time and did not differ between the normoxia
      and hypoxia conditions. In conclusion, acute exposure to normobaric hypoxia under
      thermoneutral condition in healthy men during fasting state increased lipolysis
      without affecting circulating TG.

PMID- 29466683
TI  - Mechanical testing of a steel-reinforced epoxy resin bar and clamp for external
      skeletal fixation of long-bone fractures in cats.
AB  - AIMS: To provide veterinarians with confidence when using a commercially
      available epoxy resin in external skeletal fixators (ESF), testing was conducted
      to determine exothermia during curing of the epoxy resin compared to
      polymethylmethacrylate (PMMA), the hardness of the epoxy resin as a bar over 16
      weeks, and the strength of the epoxy resin bar compared with metal clamps in
      similarly constructed Type 1a ESF constructs simulating the repair of feline long
      bone fractures. METHODS: Exothermia of the epoxy resin during curing was tested
      against PMMA with surface temperatures recorded over the first 15 minutes of
      curing, using four samples of each product. The hardness of 90 identical epoxy
      resin bars was tested by subjecting them to cyclic loads (1,000 cycles of 20.5 N,
      every 7 days) over a 16-week period and impact testing 10 bars every 2 weeks. Ten
      bars that were not subjected to cyclic loads were impact tested at 0 weeks and
      another 10 at 16 weeks. Strength of the epoxy resin product, as a bar and clamp
      composite, was tested against metal SK and Kirschner-Ehmer (KE) clamps and bars
      in Type 1a, tied-in intramedullary pin, ESF constructs with either 90 degrees  or
      75 degrees  pin placement, subjected to compressive and bending loads to 75 N.
      RESULTS: The maximum temperature during curing of the epoxy resin (min 39.8, max
      43.0) degrees C was less than the PMMA (min 85.2, max 98.5) degrees C (p<0.001).
      There was no change in hardness of the epoxy resin bars over the 16 weeks of
      cyclic loading (p=0.58). There were no differences between the median strength of
      the epoxy resin, SK or KE ESF constructs in compression or bending when tested to
      75 N (p>0.05). Stiffness of constructs with 75 degrees  pin placement was greater
      for SK than epoxy resin constructs in compression (p=0.046), and was greater for
      KE than epoxy resin constructs in bending (p=0.033). CONCLUSIONS: The epoxy resin
      tested was found to be less exothermic than PMMA; bars made from the epoxy resin
      showed durability over an expected fracture healing timeframe and had mechanical
      strength characteristics comparable to metal bar and clamp ESF constructs.
      CLINICAL RELEVANCE: The epoxy resin ESF construct tested in this study can be
      considered a suitable replacement for SK or KE ESF constructs in the treatment of
      feline long-bone fractures, in terms of mechanical strength.

PMID- 29466684
TI  - Cardiovascular response to trigeminal nerve stimulation at rest and during
      exercise in humans: does sex matter?
AB  - We sought to investigate the possibility that there are sex differences in the
      cardiovascular responses to trigeminal nerve stimulation (TGS) with cold exposure
      to the face at rest and during dynamic exercise. In 9 healthy men (age: 28 +/- 3
      yr; height: 178 +/- 1 cm; weight: 77 +/- 8 kg) and 13 women (age 26 +/- 5 yr;
      height 164 +/- 3 cm; weight 63 +/- 7 kg) beat-to-beat heart rate (HR) and blood
      pressure were recorded. Mean arterial pressure (MAP), stroke volume (SV), cardiac
      index (CI), and total vascular resistance index (TVRI) were calculated. TGS was
      applied for 3 min at rest and in-between 10-min steady-state cycling exercise at
      a HR of 110 beats/min, the measurements were obtained during the last minute of
      each period. At rest, TGS increased MAP (men: Delta18 +/- 8 mmHg; women: Delta23
      +/- 8 mmHg; means +/- SD), TVRI (men: Delta1.1 +/- 0.6 mmHg.l-1.min.m-2; women:
      Delta1.2 +/- 1.2 mmHg.l-1.min.m-2) and SV (men: Delta19 +/- 15 ml; women: Delta16
      +/- 11 ml) in both groups. CI increased with TGS in women but not in men.
      However, men presented a bradycardic response to TGS (Delta-11 +/- 8 beats/min)
      that was not significant in women compared with baseline. Cycling exercise
      increased HR, MAP, SV, and CI and decreased TVRI in men and women. TGS during
      exercise further increased MAP in men and women and did not change CI in either
      group. SV and TVRI increased with TGS during exercise only in women. TGS during
      exercise evoked bradycardia in men (Delta-7 +/- 9 beats/min), whereas HR was
      unchanged in women. Our findings indicate sex differences in TGS-related
      cardiovascular responses at rest and during exercise.

PMID- 29466685
TI  - Prolactin regulates liver growth during postnatal development in mice.
AB  - The liver grows during the early postnatal period first at slower and then at
      faster rates than the body to achieve the adult liver-to-body weight ratio (LBW),
      a constant reflecting liver health. The hormone prolactin (PRL) stimulates adult
      liver growth and regeneration, and its levels are high in the circulation of
      newborn infants, but whether PRL plays a role in neonatal liver growth is
      unknown. Here, we show that the liver produces PRL and upregulates the PRL
      receptor in mice during the first 2 wk after birth, when liver growth lags behind
      body growth. At postnatal week 4, the production of PRL by the liver ceases
      coinciding with the elevation of circulating PRL and the faster liver growth that
      catches up with body growth. PRL receptor null mice ( Prlr-/-) show a significant
      decrease in the LBW at 1, 4, 6, and 10 postnatal weeks and reduced liver
      expression of proliferation [cyclin D1 ( Ccnd1)] and angiogenesis
      [platelet/endothelial cell adhesion molecule 1 ( Pecam1)] markers relative to
      Prlr+/+ mice. However, the LBW increases in Prlr-/- mice at postnatal week 2
      concurring with the enhanced liver expression of Igf-1 and the liver upregulation
      and downregulation of suppressor of cytokine signaling 2 ( Socs2) and Socs3,
      respectively. These findings indicate that PRL acts locally and systemically to
      restrict and stimulate postnatal liver growth. PRL inhibits liver and body growth
      by attenuating growth hormone-induced Igf-1 liver expression via Socs2 and Socs3
      related mechanisms.

PMID- 29466686
TI  - Divergent effects of cold water immersion versus active recovery on skeletal
      muscle fiber type and angiogenesis in young men.
AB  - Resistance training (RT) increases muscle fiber size and induces angiogenesis to
      maintain capillary density. Cold water immersion (CWI), a common postexercise
      recovery modality, may improve acute recovery, but it attenuates muscle
      hypertrophy compared with active recovery (ACT). It is unknown if CWI following
      RT alters muscle fiber type expression or angiogenesis. Twenty-one men strength
      trained for 12 wk, with either 10 min of CWI ( n = 11) or ACT ( n = 10) performed
      following each session. Vastus lateralis biopsies were collected at rest before
      and after training. Type IIx myofiber percent decreased ( P = 0.013) and type IIa
      myofiber percent increased with training ( P = 0.012), with no difference between
      groups. The number of capillaries per fiber increased from pretraining in the CWI
      group ( P = 0.004) but not the ACT group ( P = 0.955). Expression of myosin heavy
      chain genes ( MYH1 and MYH2), encoding type IIx and IIa fibers, respectively,
      decreased in the ACT group, whereas MYH7 (encoding type I fibers) increased in
      the ACT group versus CWI ( P = 0.004). Myosin heavy chain IIa protein increased
      with training ( P = 0.012) with no difference between groups. The proangiogenic
      vascular endothelial growth factor protein decreased posttraining in the ACT
      group versus CWI ( P < 0.001), whereas antiangiogenic Sprouty-related, EVH1
      domain-containing protein 1 protein increased with training in both groups ( P =
      0.015). Expression of microRNAs that regulate muscle fiber type (miR-208b and 
      499a) and angiogenesis (miR-15a, -16, and -126) increased only in the ACT group (
      P < 0.05). CWI recovery after each training session altered the angiogenic and
      fiber type-specific response to RT through regulation at the levels of microRNA,
      gene, and protein expression.

PMID- 29466687
TI  - The 2018 New Investigator Review Awards.

PMID- 29466688
TI  - The Efficacy of Platelet-Rich Plasma and Platelet-Rich Fibrin in Arthroscopic
      Rotator Cuff Repair: A Meta-analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Basic science studies suggest that platelet-rich therapies have a
      positive effect on tendon repair. However, the clinical evidence is conflicted on
      whether this translates to increased tendon healing and improved functional
      outcomes. PURPOSE: To perform a systematic review of randomized controlled trials
      (RCTs) in the literature to ascertain whether platelet-rich plasma (PRP) or
      platelet-rich fibrin (PRF) improved patient outcomes in arthroscopic rotator cuff
      repair. STUDY DESIGN: Meta-analysis. METHODS: Two independent reviewers performed
      the literature search based on the PRISMA (Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses) guidelines, with a third author resolving
      any discrepancies. RCTs comparing PRP or PRF to a control in rotator cuff repair
      were included. Quality of evidence was assessed using the Jadad score. Clinical
      outcomes were compared using the risk ratio for dichotomous variables and the
      mean difference for continuous variables. A P value <.05 was deemed statistically
      significant. RESULTS: Eighteen RCTs with 1147 patients were included in this
      review. PRP resulted in significantly decreased rates of incomplete tendon
      healing for all tears combined (17.2% vs 30.5%, respectively; P < .05),
      incomplete tendon healing in small-medium tears (22.4% vs 38.3%, respectively; P
      < .05), and incomplete tendon healing in medium-large tears (12.3% vs 30.5%,
      respectively; P < .05) compared to the control. There was a significant result in
      favor of PRP for the Constant score (85.6 vs 83.1, respectively; P < .05) and the
      visual analog scale score for pain at 30 days postoperatively (2.9 vs 4.3,
      respectively; P < .05) and at final follow-up (1.2 vs 1.4, respectively; P < .05)
      compared to the control. PRF did not result in a significantly decreased rate of
      incomplete tendon healing for all tears combined (23.0% vs 24.6%, respectively; P
      = .74) or an improved Constant score (80.8 vs 79.8, respectively; P = .27)
      compared to the control. PRF resulted in a significantly longer operation time
      (99.1 vs 83.3 minutes, respectively; P< .05) compared to the control. CONCLUSION:
      The current evidence indicates that the use of PRP in rotator cuff repair results
      in improved healing rates, pain levels, and functional outcomes. In contrast, PRF
      has been shown to have no benefit in improving tendon healing rates or functional
      outcomes.

PMID- 29466689
TI  - The protective effects of gonadotropin-releasing hormone agonist on ovarian
      functions in breast Cancer patients receiving chemotherapy.
AB  - In recent decades, the incidence rate of breast cancer has increased dramatically
      worldwide and has become one of the most prevalent cancers in women. According to
      the global data provided by the WHO, there were more than 1.7 million new cases
      of breast cancer in 2012, accounting for 25% of all reported cancer cases and 15%
      of all reported deaths among females. To most young patients, especially those
      younger than 40 years of age, chemotherapy should be taken into consideration as
      a treatment modality, even if the tumor size is small or without lymphatic
      metastasis. A significant portion of the patients will suffer from the side
      effects that result from long-term chemotherapy regimens, such as
      myelosuppression, heart failure, and development of a second primary malignancy.
      Ovarian suppression and premature ovarian failure (POF) are the most common side
      effects reported as they have notable clinical symptoms; the incidence rates have
      been reported to be in a range of 10-90%. Gonadotropin-releasing hormone agonists
      (GnRH-a), also termed luteinizing hormone release hormone agonists (LHRH-a), may
      very well offer a solution to treating these side effects. This article aims to
      summarize advanced studies concerning protective effects of GnRH-a on ovarian
      functions in the setting of breast cancer under chemotherapy.

PMID- 29466690
TI  - Safety and efficacy of etanercept-methotrexate combination therapy in patients
      with rhupus: an observational study of non-glucocorticoid treatment for rheumatic
      diseases.
AB  - OBJECTIVES: To evaluate the safety and efficacy of etanercept (ETN) plus
      methotrexate (MTX) in patients with rhupus without using corticosteroids.
      METHODS: Twenty rhupus patients [meeting the criteria for both rheumatoid
      arthritis (RA) and systemic lupus erythematosus (SLE)] who had never been treated
      with corticosteroids, DMARDs, or biological agents with a 28-joint Disease
      Activity Score (DAS28) >3.2 and lupus nephritis determined from histopathological
      specimens were enrolled. All patients were treated with MTX plus ETN, and
      monitored for 24 weeks of treatment. Clinical efficacy was evaluated using the
      DAS28 and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K).
      Demographic characteristics, clinical parameters, and treatment data were
      analyzed at baseline (BL) and after 4, 8, 16, and 24 weeks of treatment. The
      incidence of adverse events (AEs) was evaluated. RESULTS: The 20 patients had a
      mean age of 44.3+/-8 years and a disease duration of 5.4+/-3.1 years. At week 24,
      treatment with ETN plus MTX resulted in a significant improvement in DAS28 (3.3+/
      0.1 vs. 6.0+/-0.1 /BL; p<0.001), tender joint count (2.9+/-0.2 vs. 10.75+/
      0.8/BL; p<0.001), swollen joint count (2.7+/-0.2 vs. 8.5+/-0.5/BL; p<0.001),
      Visual Analog Scale for pain (27.0+/-2.6 mm vs. 66.5+/-3.1 mm/BL; p<0.001), and
      SLEDAI-2K (6.30+/-0.36 vs. 13.7+/-0.48/BL; p<0.001). During the study, the most
      frequent AEs were upper respiratory tract infections (10%), injection site
      reactions (10%), and cutaneous rashes (5%); there were no serious AEs. No deaths,
      malignancies, or tuberculosis or other serious infections were reported.
      CONCLUSION: Without corticosteroids, combination therapy of ETN plus MTX was
      relatively safe and effective in rhupus patients, which indicates efficacy of non
      corticosteroid treatment for rhupus.

PMID- 29466691
TI  - Role of production of type I interferons by B cells in the mechanisms and
      pathogenesis of systemic lupus erythematosus.
AB  - Type I interferons (IFNs) have a prominent role in many aspects of normal innate
      and adaptive immunity and autoimmunity. However, cell-type specific information
      about type I IFN expression and autocrine/paracrine signaling is sparse and
      mostly focused on non-lymphocyte and non-immune cell populations. A major
      function of B cells is cytokine production, but surprisingly, type I IFN
      production by B cells in systemic lupus erythematosus (SLE) has not been
      thoroughly investigated. This is due, in part, to the established view that
      plasmacytoid dendritic cells (pDCs) are the primary source of pathogenic type I
      IFN in lupus. Recent studies, however, have provided evidence to challenge this
      paradigm. Here, we discuss data supporting a new concept that the production of
      type I IFN, especially IFNbeta, by early stage transitional B cells may be an
      important source of type I IFN to support autoreactive B cell development in
      lupus. These findings, if confirmed, may provide a new paradigm in designing and
      developing more effective therapies for preventing the formation of autoreactive
      B cells.

PMID- 29466692
TI  - Anti-programmed cell death-1 (PD-1) monoclonal antibodies in treating advanced
      melanoma -- a clinical update.
AB  - Since their approval by regulatory agencies worldwide, the anti-PD-1 monoclonal
      antibodies (mAbs), as monotherapy or in combination with ipilimumab, have become
      the standard frontline therapy for advanced BRAF-wild-type melanoma and an
      eminent rival to targeted therapy in the first-line setting for unresectable BRAF
      mutated melanoma. Mature survival data from randomized phase 3 trials have
      emerged, confirming their position in the current treatment schema for advanced
      melanoma. Recently, the clinical utility of anti-PD-1 agents has extended into
      other disease settings, such as resected high-risk melanomas, non-cutaneous
      subtypes, and brain metastases. How to best combat resistance to anti-PD-1 mAbs
      remains the major focus of clinical investigations. This review aims to provide
      an update on the recent progress and current challenges relating to the clinical
      application of anti-PD-1 agents in the treatment of advanced melanoma.

PMID- 29466693
TI  - Acute extracellular matrix, inflammatory and MAPK response to lengthening
      contractions in elderly human skeletal muscle.
AB  - To uncover potential factors that may be involved in the impaired regenerative
      capacity of aged skeletal muscle, we comprehensively assessed the molecular
      stress response following muscle damage in old and young individuals. 10 young
      (22.7 +/- 2.25 yrs) and 8 physically active old (70.9 +/- 7.5 yrs) subjects
      completed a bout of 300 lengthening contractions (LC), and muscle biopsies were
      taken pre-exercise and at 3, 24, and 72 h post-LC. Both age groups performed the
      same amount of work during LC, with the old group displaying a resistance to LC
      induced fatigue during the exercise. Muscle damage was evident by soreness and
      losses in isokinetic force and power production, though older subjects
      experienced reduced force and power losses relative to the young group. The acute
      extracellular matrix (ECM) response was characterized by substantial increases in
      the glycoproteins tenascin C and fibronectin in the young, which were blunted in
      the old muscle following damage. Old muscle displayed a generally heightened and
      asynchronous inflammatory response compared to young muscle, with higher
      expression of MCP-1 that appeared at later time points, and increased NF-kappab
      activity. Expression of the stress-related MAPKs P38 and JNK increased only in
      the old groups following muscle damage. In summary, aberrations appear in the
      inflammatory, ECM and MAPK responses of aged skeletal muscle following damaging
      LC, each of which may individually or collectively contribute to the
      deterioration of muscle repair mechanisms that accompanies aging.

PMID- 29466694
TI  - Lipid pathway deregulation in advanced prostate cancer.
AB  - The link between prostate cancer (PC) development and lipid metabolism is well
      established, with AR intimately involved in a number of lipogenic processes
      involving SREBP1, PPARG, FASN, ACC, ACLY and SCD1. Recently, there is growing
      evidence implicating the role of obesity and peri-prostatic adipose tissue (PPAT)
      in PC aggressiveness and related mortality, suggesting the importance of lipid
      pathways in both localised and disseminated disease. A number of promising agents
      are in development to target the lipogenic axis in PC, and the likelihood is that
      these agents will form part of combination drug strategies, with targeting of
      multiple metabolic pathways (e.g. FASN and CPT1), or in combination with AR
      pathway inhibitors (SCD1 and AR).

PMID- 29466695
TI  - Molecular mechanisms and therapeutic targets in neuroblastoma.
AB  - Neuroblastoma is the most common extracranical tumor of childhood and the most
      deadly tumor of infancy. It is characterized by early age onset and high
      frequencies of metastatic disease but also the capacity to spontaneously regress.
      Despite intensive therapy, the survival for patients with high-risk neuroblastoma
      and those with recurrent or relapsed disease is low. Hence, there is an urgent
      need to develop new therapies for these patient groups. The molecular
      pathogenesis based on high-throughput omics technologies of neuroblastoma is
      beginning to be resolved which have given the opportunity to develop personalized
      therapies for high-risk patients. Here we discuss the potential of developing
      targeted therapies against aberrantly expressed molecules detected in sub
      populations of neuroblastoma patients and how these selected targets can be
      drugged in order to overcome treatment resistance, improve survival and quality
      of life for these patients and also the possibilities to transfer preclinical
      research into clinical testing.

PMID- 29466696
TI  - UHRF1 regulates CDH1 via promoter associated non-coding RNAs in prostate cancer
      cells.
AB  - Non-coding RNAs (ncRNAs) transcribed from the promoter and the downstream region
      can affect the expression of the corresponding coding genes. It has been shown
      that sense-directed ncRNAs arising from the promoter region of the E-cadherin
      gene (CDH1) mediate its repression. Here, we show that an antisense-directed
      ncRNA (paRCDH1-AS) transcribed from the CDH1 promoter is necessary for its
      expression. paRCDH1-AS acts as a hooking scaffold by recruiting the epigenetic
      regulators, UHRF1, DNMT3A, SUV39H1 and SUZ12, involved in CDH1 repression. The
      binding of epigenetic regulators to paCRDH1-AS, indeed, prevents their
      localization to the chromatin on CDH1 promoter. Moreover, paRCDH1-AS silencing
      induces CDH1 repression and a switch of the epigenetic profile on the promoter
      towards a more closed chromatin. Using bioinformatic and experimental approaches
      we defined that the promoter of the paRCDH1-AS is shared with the E-cadherin
      gene, showing a bidirectional promoter activity. We found that UHRF1 controls
      both CDH1 and paRCDH1-AS by directly binding this bidirectional promoter region.
      Our study provides evidences, for the first time, that UHRF1 recruitment can be
      affected by promoter-associated non-coding RNAs, opening new perspective
      regarding the role of UHRF1 in these complex regulatory networks.

PMID- 29466697
TI  - Cdk-related kinase 9 regulates RNA polymerase II mediated transcription in
      Toxoplasma gondii.
AB  - Cyclin-dependent kinases are an essential part of eukaryotic transcriptional
      machinery. In Apicomplexan parasites, the role and relevance of the kinases in
      the multistep process of transcription seeks more attention given the absence of
      full repertoire of canonical Cdks and cognate cyclin partners. In this study, we
      functionally characterize T. gondii Cdk-related kinase 9 (TgCrk9) showing maximal
      homology to eukaryotic Cdk9. An uncanonical cyclin, TgCyclin L, colocalizes with
      TgCrk9 in the parasite nucleus and co-immunoprecipitate, could activate the
      kinase in-vitro. We identify two threonines in conserved T-loop domain of TgCrk9
      that are important for its activity. The activated TgCrk9 phosphorylates C
      terminal domain (CTD) of TgRpb1, the largest subunit of RNA polymerase II
      highlighting its role in transcription. Selective chemical inhibition of TgCrk9
      affected serine 2 phosphorylation in the heptapeptide repeats of TgRpb1-CTD
      towards 3' end of genes consistent with a possible role in transcription
      elongation. Interestingly, TgCrk9 kinase activity is regulated by the upstream
      TgCrk7 based CAK complex. TgCrk9 was found to functionally complement the role of
      its yeast counterpart Bur1 establishing its role as an important transcriptional
      kinase. In this study, we provide robust evidence that TgCrk9 is an important
      part of transcription machinery regulating gene expression in T. gondii.

PMID- 29466699
TI  - Unveiling network-based functional features through integration of gene
      expression into protein networks.
AB  - Decoding health and disease phenotypes is one of the fundamental objectives in
      biomedicine. Whereas high-throughput omics approaches are available, it is
      evident that any single omics approach might not be adequate to capture the
      complexity of phenotypes. Therefore, integrated multi-omics approaches have been
      used to unravel genotype-phenotype relationships such as global regulatory
      mechanisms and complex metabolic networks in different eukaryotic organisms. Some
      of the progress and challenges associated with integrated omics studies have been
      reviewed previously in comprehensive studies. In this work, we highlight and
      review the progress, challenges and advantages associated with emerging
      approaches, integrating gene expression and protein-protein interaction networks
      to unravel network-based functional features. This includes identifying disease
      related genes, gene prioritization, clustering protein interactions, developing
      the modules, extract active subnetworks and static protein complexes or
      dynamic/temporal protein complexes. We also discuss how these approaches
      contribute to our understanding of the biology of complex traits and diseases.
      This article is part of a Special Issue entitled: Cardiac adaptations to obesity,
      diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B.
      Dyck and Christine Des Rosiers.

PMID- 29466698
TI  - ERK1/2/mTOR/Stat3 pathway-mediated autophagy alleviates traumatic brain injury
      induced acute lung injury.
AB  - Acute lung injury (ALI) is one of several complications in patients with
      traumatic brain injury (TBI). Autophagy is a primary homeostatic process that
      promotes cell survival under stress. Accumulating evidence implicates autophagy
      in the pathogenesis of ALI under various conditions. However, the role of
      autophagy in TBI-induced ALI remains unknown. The aim of this study was to adjust
      autophagy with pharmacological agents to determine its functional significance in
      TBI-induced ALI. Rats were preconditioned with autophagy promoter rapamycin or
      inhibitor 3-methyladenine before they were challenged with TBI. Extracellular
      signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126, mechanistic target of
      rapamycin (mTOR) inhibitor rapamycin, and signal transducer and activator of
      transcription 3 (Stat3) inhibitor S31-201 were used to test the role of
      ERK1/2/mTOR/Stat3 signaling pathway in regulating autophagy. Autophagy is
      activated in lung tissues after TBI. Enhancement of autophagy suppressed
      apoptosis, inflammation and oxidative stress in lung tissues, which were
      activated after TBI, whereas inhibition of autophagy aggravated these critical
      pathological changes. Autophagy also improved TBI-induced impairment in pulmonary
      barrier function, oxygenation function and static compliance. Furthermore, TBI
      induced autophagy was mediated by ERK1/2/mTOR/Stat3 pathway, which may serve to
      reduce ALI and improve pulmonary barrier function, oxygenation function and
      static compliance. These findings are important for the prevention and treatment
      of TBI-induced ALI.

PMID- 29466700
TI  - Engineering of new-to-nature halogenated indigo precursors in plants.
AB  - Plants are versatile chemists producing a tremendous variety of specialized
      compounds. Here, we describe the engineering of entirely novel metabolic pathways
      in planta enabling generation of halogenated indigo precursors as non-natural
      plant products. Indican (indolyl-beta-D-glucopyranoside) is a secondary
      metabolite characteristic of a number of dyers plants. Its deglucosylation and
      subsequent oxidative dimerization leads to the blue dye, indigo. Halogenated
      indican derivatives are commonly used as detection reagents in histochemical and
      molecular biology applications; their production, however, relies largely on
      chemical synthesis. To attain the de novo biosynthesis in a plant-based system
      devoid of indican, we employed a sequence of enzymes from diverse sources,
      including three microbial tryptophan halogenases substituting the amino acid at
      either C5, C6, or C7 of the indole moiety. Subsequent processing of the
      halotryptophan by bacterial tryptophanase TnaA in concert with a mutant of the
      human cytochrome P450 monooxygenase 2A6 and glycosylation of the resulting
      indoxyl derivatives by an endogenous tobacco glucosyltransferase yielded
      corresponding haloindican variants in transiently transformed Nicotiana
      benthamiana plants. Accumulation levels were highest when the 5-halogenase PyrH
      was utilized, reaching 0.93 +/- 0.089 mg/g dry weight of 5-chloroindican. The
      identity of the latter was unambiguously confirmed by NMR analysis. Moreover, our
      combinatorial approach, facilitated by the modular assembly capabilities of the
      GoldenBraid cloning system and inspired by the unique compartmentation of plant
      cells, afforded testing a number of alternative subcellular localizations for
      pathway design. In consequence, chloroplasts were validated as functional
      biosynthetic venues for haloindican, with the requisite reducing augmentation of
      the halogenases as well as the cytochrome P450 monooxygenase fulfilled by
      catalytic systems native to the organelle. Thus, our study puts forward a viable
      alternative production platform for halogenated fine chemicals, eschewing
      reliance on fossil fuel resources and toxic chemicals. We further contend that in
      planta generation of halogenated indigoid precursors previously unknown to nature
      offers an extended view on and, indeed, pushes forward the established frontiers
      of biosynthetic capacity of plants.

PMID- 29466701
TI  - Interaction between amyloidogenic proteins and biomembranes in protein misfolding
      diseases: Mechanisms, contributors, and therapy.
AB  - The toxic deposition of misfolded amyloidogenic proteins is associated with more
      than fifty protein misfolding diseases (PMDs), including Alzheimer's disease,
      Parkinson's disease and type 2 diabetes mellitus. Protein deposition is a multi
      step process modulated by a variety of factors, in particular by membrane-protein
      interaction. The interaction results in permeabilization of biomembranes
      contributing to the cytotoxicity that leads to PMDs. Different biological and
      physiochemical factors, such as protein sequence, lipid composition, and
      chaperones, are known to affect the membrane-protein interaction. Here, we
      provide a comprehensive review of the mechanisms and contributing factors of the
      interaction between biomembranes and amyloidogenic proteins, and a summary of the
      therapeutic approaches to PMDs that target this interaction. This article is part
      of a Special Issue entitled: Protein Aggregation and Misfolding at the Cell
      Membrane Interface edited by Ayyalusamy Ramamoorthy.

PMID- 29466702
TI  - Inflammasome biology, molecular pathology and therapeutic implications.
AB  - Inflammasomes are intracellular multiprotein signaling complexes, mainly present
      in myeloid cells. They commonly assemble around a cytoplasmic receptor of the
      nucleotide-binding leucine-rich repeat containing receptor (NLR) family, although
      other cytoplasmic receptors like pyrin have been shown to form inflammasomes. The
      nucleation of the multiprotein scaffolding platform occurs upon detection of a
      microbial, a danger or a homeostasis pattern by the receptor that will, most
      commonly, associate with the adaptor protein ASC (apoptosis-associated speck-like
      protein containing a CARD) through homotypic domain interactions resulting in
      recruitment of procaspase-1. This will lead to the autoproteolytic activation of
      caspase-1, which regulates the secretion of proinflammatory IL1beta and IL18
      cytokines and pyroptosis, a caspase-1-mediated form of cell death. Pyroptosis
      occurs through cleavage of Gasdermin D, a membrane pore forming protein.
      Recently, non-canonical inflammasomes have been described, which directly sense
      intracellular pathogens through caspase-4 and -5 in humans, leading to
      pyroptosis. Inflammasomes are important in host defense; however, a deregulated
      activity is associated with a number of inflammatory, immune and metabolic
      disorders. Furthermore, mutations in inflammasome receptor coding genes are
      causal for an increasing number of rare autoinflammatory diseases. Biotherapies
      targeting the products of inflammasome activation as well as molecules that
      directly or indirectly inhibit inflammasome nucleation and activation are
      promising therapeutic areas. This review discusses recent advances in
      inflammasome biology, the molecular pathology of several inflammasomes, and
      current therapeutic approaches in autoinflammatory diseases and in selected
      common multifactorial inflammasome-mediated disorders.

PMID- 29466703
TI  - sAPPbeta and sAPPalpha increase structural complexity and E/I input ratio in
      primary hippocampal neurons and alter Ca2+ homeostasis and CREB1-signaling.
AB  - One major pathophysiological hallmark of Alzheimer's disease (AD) is senile
      plaques composed of amyloid beta (Abeta). In the amyloidogenic pathway, cleavage
      of the amyloid precursor protein (APP) is shifted towards Abeta production and
      soluble APPbeta (sAPPbeta) levels. Abeta is known to impair synaptic function;
      however, much less is known about the physiological functions of sAPPbeta. The
      neurotrophic properties of sAPPalpha, derived from the non-amyloidogenic pathway
      of APP cleavage, are well-established, whereas only a few, conflicting studies on
      sAPPbeta exist. The intracellular pathways of sAPPbeta are largely unknown. Since
      sAPPbeta is generated alongside Abeta by beta-secretase (BACE1) cleavage, we
      tested the hypothesis that sAPPbeta effects differ from sAPPalpha effects as a
      neurotrophic factor. We therefore performed a head-to-head comparison of both
      mammalian recombinant peptides in developing primary hippocampal neurons (PHN).
      We found that sAPPalpha significantly increases axon length (p = 0.0002) and that
      both sAPPalpha and sAPPbeta increase neurite number (p < 0.0001) of PHN at 7 days
      in culture (DIV7) but not at DIV4. Moreover, both sAPPalpha- and sAPPbeta-treated
      neurons showed a higher neuritic complexity in Sholl analysis. The number of
      glutamatergic synapses (p < 0.0001), as well as layer thickness of postsynaptic
      densities (PSDs), were significantly increased, and GABAergic synapses decreased
      upon sAPP overexpression in PHN. Furthermore, we showed that sAPPalpha enhances
      ERK and CREB1 phosphorylation upon glutamate stimulation at DIV7, but not DIV4 or
      DIV14. These neurotrophic effects are further associated with increased glutamate
      sensitivity and CREB1-signaling. Finally, we found that sAPPalpha levels are
      significantly reduced in brain homogenates of AD patients compared to control
      subjects. Taken together, our data indicate critical stage-dependent roles of
      sAPPs in the developing glutamatergic system in vitro, which might help to
      understand deleterious consequences of altered APP shedding in AD patients,
      beyond Abeta pathophysiology.

PMID- 29466704
TI  - A robust SSFP technique for fMRI at ultra-high field strengths.
AB  - A non-balanced (nb) SSFP-based fMRI method based on CE-FAST is presented to
      alleviate some shortcomings of high spatial-specificity techniques commonly used
      in high static magnetic fields. The proposed sequence does not suffer from the
      banding artifacts inherent to balanced (b) SSFP, has low geometrical distortions
      and SAR compared to spin-echo EPI, and in contrast to previous nbSSFP
      implementations, is applied at a TR, theoretically prescribed for the optimum
      contrast. Its non-balanced gradient was chosen to just dephase the unwanted
      signal component (2pi dephasing per TR per voxel). 3D data were acquired from
      nine healthy subjects, who performed a visual-motor task on a 7 Tesla scanner.
      For comparison, experiments were accompanied by similar bSSFP and spin-echo
      acquisitions. Consistent activation was achieved in all subjects with
      theoretically optimal TR, in contrast to previous nbSSFP techniques. The signal
      stability as well as relative and absolute functional signal changes, were found
      to be comparable with bSSFP and spin-echo techniques. The results suggest that
      with suitable modifications, CE-FAST can be regarded as a robust SSFP-based
      method for high spatial specificity fMRI techniques.

PMID- 29466705
TI  - Synonymous Mutations at the Beginning of the Influenza A Virus Hemagglutinin Gene
      Impact Experimental Fitness.
AB  - The fitness effects of synonymous mutations can provide insights into biological
      and evolutionary mechanisms. We analyzed the experimental fitness effects of all
      single-nucleotide mutations, including synonymous substitutions, at the beginning
      of the influenza A virus hemagglutinin (HA) gene. Many synonymous substitutions
      were deleterious both in bulk competition and for individually isolated clones.
      Investigating protein and RNA levels of a subset of individually expressed HA
      variants revealed that multiple biochemical properties contribute to the observed
      experimental fitness effects. Our results indicate that a structural element in
      the HA segment viral RNA may influence fitness. Examination of naturally evolved
      sequences in human hosts indicates a preference for the unfolded state of this
      structural element compared to that found in swine hosts. Our overall results
      reveal that synonymous mutations may have greater fitness consequences than
      indicated by simple models of sequence conservation, and we discuss the
      implications of this finding for commonly used evolutionary tests and analyses.

PMID- 29466706
TI  - Identification and characterization of Taenia solium enolase as a plasminogen
      binding protein.
AB  - The larval stage of Taenia solium (cysticerci) is the causal agent of human and
      swine cysticercosis. When ingested by the host, T. solium eggs are activated and
      hatch in the intestine, releasing oncospheres that migrate to various tissues and
      evolve into cysticerci. Plasminogen (Plg) receptor proteins have been reported to
      play a role in migration processes for several pathogens. This work is aimed to
      identify Plg-binding proteins in T. solium cysticerci and determine whether T.
      solium recombinant enolase (rTsEnoA) is capable of specifically binding and
      activating human Plg. To identify Plg-binding proteins, a 2D-SDS-PAGE ligand
      blotting was performed, and recognized spots were identified by MS/MS. Seven
      proteins from T. solium cysticerci were found capable of binding Plg: fascicilin
      1, fasciclin-2, enolase, MAPK, annexin, actin, and cytosolic malate
      dehydrogenase. To determine whether rTsEnoA binds human Plg, a ligand blotting
      was performed and the results were confirmed by ELISA both in the presence and
      absence of epsilonACA, a competitive Plg inhibitor. Finally, rTsEnoA-bound Plg
      was activated to plasmin in the presence of tPA. To better understand the
      evolution of enolase isoforms in T. solium, a phylogenetic inference analysis
      including 75 enolase amino acid sequences was conducted. The origin of flatworm
      enolase isoforms, except for Eno4, is independent of their vertebrate
      counterparts. Therefore, herein we propose to designate tapeworm protein isoforms
      as A, B, C, and 4. In conclusion, recombinant enolase showed a strong plasminogen
      binding and activating activity in vitro. T. solium enolase could play a role in
      parasite invasion along with other plasminogen-binding proteins.

PMID- 29466708
TI  - GNIP1 E3 ubiquitin ligase is a novel player in regulating glycogen metabolism in
      skeletal muscle.
AB  - BACKGROUND: Glycogenin-interacting protein 1 (GNIP1) is a tripartite motif (TRIM)
      protein with E3 ubiquitin ligase activity that interacts with glycogenin. These
      data suggest that GNIP1 could play a major role in the control of glycogen
      metabolism. However, direct evidence based on functional analysis remains to be
      obtained. OBJECTIVES: The aim of this study was 1) to define the expression
      pattern of glycogenin-interacting protein/Tripartite motif containing protein 7
      (GNIP/TRIM7) isoforms in humans, 2) to test their ubiquitin E3 ligase activity,
      and 3) to analyze the functional effects of GNIP1 on muscle glucose/glycogen
      metabolism both in human cultured cells and in vivo in mice. RESULTS: We show
      that GNIP1 was the most abundant GNIP/TRIM7 isoform in human skeletal muscle,
      whereas in cardiac muscle only TRIM7 was expressed. GNIP1 and TRIM7 had
      autoubiquitination activity in vitro and were localized in the Golgi apparatus
      and cytosol respectively in LHCN-M2 myoblasts. GNIP1 overexpression increased
      glucose uptake in LHCN-M2 myotubes. Overexpression of GNIP1 in mouse muscle in
      vivo increased glycogen content, glycogen synthase (GS) activity and phospho-GSK
      3alpha/beta (Ser21/9) and phospho-Akt (Ser473) content, whereas decreased GS
      phosphorylation in Ser640. These modifications led to decreased blood glucose
      levels, lactate levels and body weight, without changing whole-body insulin or
      glucose tolerance in mouse. CONCLUSION: GNIP1 is an ubiquitin ligase with a
      markedly glycogenic effect in skeletal muscle.

PMID- 29466707
TI  - Iron transport kinetics through blood-brain barrier endothelial cells.
AB  - BACKGROUND: Transferrin and its receptors play an important role during the
      uptake and transcytosis of iron through blood-brain barrier (BBB) endothelial
      cells (ECs) to maintain iron homeostasis in BBB endothelium and brain. Any
      disruptions in the cell environment may change the distribution of transferrin
      receptors on the cell surface, which eventually alter the homeostasis and
      initiate neurodegenerative disorders. In this paper, we developed a comprehensive
      mathematical model that considers the necessary kinetics for holo-transferrin
      internalization and acidification, apo-transferrin recycling, and exocytosis of
      free iron and transferrin-bound iron through basolateral side of BBB ECs.
      METHODS: Ordinary differential equations are formulated based on the first order
      reaction kinetics to model the iron transport considering their interactions with
      transferrin and transferrin receptors. Unknown kinetics rate constants are
      determined from experimental data by applying a non-linear optimization
      technique. RESULTS: Using the estimated kinetic rate constants, the presented
      model can effectively reproduce the experimental data of iron transports through
      BBB ECs for many in-vitro studies. Model results also suggest that the BBB ECs
      can regulate the extent of the two possible iron transport pathways (free and
      transferrin-bound iron) by controlling the receptor expression, internalization
      of holo-transferrin-receptor complexes and acidification of holo-transferrin
      inside the cell endosomes. CONCLUSION: The comprehensive mathematical model
      described here can predict the iron transport through BBB ECs considering various
      possible routes from blood side to brain side. The model can also predict the
      transferrin and iron transport behavior in iron-enriched and iron-depleted cells,
      which has not been addressed in previous work.

PMID- 29466709
TI  - Gastrointestinal hormones in regulation of memory.
AB  - The connection between the gastrointestinal hormones and the brain has been
      established many years ago. This relation is termed the gut-brain axis (GBA). The
      GBA is a bidirectional communication which not only regulates gastrointestinal
      homeostasis but is also linked with higher emotional and cognitive functions.
      Hypothalamus plays a critical role in the regulation of energy metabolism,
      nutrient partitioning and control of feeding behaviors. Various gut hormones are
      released inside the gastrointestinal tract on food intake. These hormones act
      peripherally and influence the different responses of the tissues to the food
      intake, but do also have effects on the brain. The hypothalamus, in turn,
      integrates visceral function with limbic system structures such as hippocampus,
      amygdala, and cerebral cortex. The hippocampus has been known for its involvement
      in the cognitive function and the modulation of synaptic plasticity. This review
      aims to establish the role of various gut hormones in learning and memory,
      through the interaction of various receptors in the hippocampus. Understanding
      their role in memory can also aid in finding novel therapeutic strategies for the
      treatment of the neurological disorders associated with memory dysfunctions.

PMID- 29466710
TI  - Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS
      phosphorylation.
AB  - Uncoupled endothelial nitric oxide synthase (eNOS) produces O2- instead of nitric
      oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of
      cellular proliferation, attenuated low shear stress (SS) induced O2- production.
      Nevertheless, it is unclear whether autophagy plays a critical role in the
      regulation of eNOS uncoupling. Therefore, this study aimed to investigate the
      modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found
      that low SS induced endothelial O2- burst, which was accompanied by reduced NO
      release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low
      SS-induced O2- releasing, indicating eNOS uncoupling. Autophagy markers such as
      LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low
      SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced,
      implying impaired autophagic flux. Interestingly, low SS-induced NO reduction
      could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via
      restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS
      uncoupling might be ascribed to autophagic flux blockade because phosphorylation
      of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In
      contrast, eNOS acetylation was not found to be regulated by low SS and autophagy.
      Notably, although low SS had no influence on eNOS Ser1177 phosphorylation,
      whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the
      eNOS recoupling through restoration of autophagic flux. Taken together, we
      reported a novel mechanism for regulation of eNOS uncoupling by low SS via
      autophagy-mediated eNOS phosphorylation, which is implicated in geometrical
      nature of atherogenesis.

PMID- 29466711
TI  - Colorimetric detection of 1,5-anhydroglucitol based on graphene quantum dots and
      enzyme-catalyzed reaction.
AB  - Early diagnosis of diabetes yields significant clinical benefits. The serum level
      of 1,5-anhydroglucitol (1,5-AG) has been a new biochemical marker for
      postprandial hyperglycemia. In this study, a simple colorimetric method for 1,5
      AG detection has been designed based on highly efficient peroxidase mimetic
      activity of GQDs and enzyme-catalyzed reaction. By the catalytic action of
      pyranose oxidase (PROD), the 1,5-AG was oxidized to 1,5-anhydrofuctose and H2O2.
      The GQDs in the presence of H2O2 exhibited highly efficient catalytic activity
      toward the oxidation of 3, 3', 5, 5'-tetramethylbenzidine (TMB) to a blue colored
      product. The influence of relevant experimental variables was optimized. A linear
      relationship of optical signal with the concentration of 1,5-AG in the range of
      20.0-100.0MUg/mL with the regression correlation coefficient of 0.9985 was
      obtained which could be monitored by colorimetry detection. The limit of
      detection (LOD) for 1,5-AG detection was approximately 0.144MUg/mL. All in all,
      the proposed 1,5-AG detection system based on GQDs and PROD-catalyzed reaction
      showed better performances with simple operation, low-cost, higher selectivity.

PMID- 29466712
TI  - Dihydrolipoamide dehydrogenase from Leishmania donovani: New insights through
      biochemical characterization.
AB  - Dihydrolipoamide dehydrogenase (DLDH) regulates many crucial metabolic pathways
      as a multi-enzyme complex. Leishmania donovani dihydrolipoamide dehydrogenase
      (LdDLDH) has two variants present on two different chromosomes with very less
      sequence similarities. In the current study, we cloned both the variants in
      pET28a (+) vector and expressed in Rosetta-gami (DE3) E. coli strain. Expressed
      proteins were finally purified from pellets using Ni-NTA affinity chromatography.
      Purified enzymes were biochemically characterized and different kinetic
      parameters were studied. Both the variants showed maximum activity in pH range of
      7.0-8.0 and temperature 50+/-5 degrees C in the physiological direction. The
      estimated Km for dihydrolipoamide (DLA) and NAD+ were 2.7+/-0.48mM and 171.23+/
      11.59MUM respectively for variant 1 (LdBPK291950.1). In the case of variant 2
      (LdBPK323510.1), Km values for DLA and NAD+ were found to be 829.85+/-37MUM and
      226+/-1.56MUM respectively. The variant 2 was more efficient in terms of
      activity. While both the forms of the enzymes showed diaphorase activity, variant
      1 was found to be better. Sequence dissimilarities of both forms were analyzed
      for biological insights.

PMID- 29466713
TI  - Daily maternal separations during stress hyporesponsive period decrease the
      thresholds of panic-like behaviors to electrical stimulation of the dorsal
      periaqueductal gray of the adult rat.
AB  - The present study examined whether early life maternal separation (MS), a model
      of childhood separation anxiety, predisposes to panic at adulthood. For this
      purpose, male pups were submitted to 3-h daily maternal separations along
      postnatal (PN) days of either the 'stress hyporesponsive period' (SHRP) from PN4
      to PN14 (MS11) or throughout lactation from PN2 to PN21 (MS20). Pups were further
      reunited to conscious (CM) or anesthetized (AM) mothers to assess the effect of
      mother-pup interaction upon reunion. Controls were subjected to brief handling
      (15 s) once a day throughout lactation (BH20). As adults (PN60), rats were tested
      for the thresholds to evoke panic-like behaviors upon electrical stimulation of
      dorsal periaqueductal gray matter and exposed to an elevated plus-maze, an open
      field, a forced swim and a sucrose preference test. A factor analysis was also
      performed to gain insight into the meaning of behavioral tests. MS11-CM rather
      than MS20-CM rats showed enhanced panic responses and reductions in both swimming
      and sucrose preference. Panic facilitations were less intense in mother-neglected
      rats. Although MS did not affect anxiety, MS11-AM showed robust reductions of
      defecation in an open-field. Factor analysis singled out anxiety, hedonia,
      exploration, coping and gut activity. Although sucrose preference and coping
      loaded on separate factors, appetite (adult weight) correlated with active coping
      in both forced swim and open-field (central area exploration). Concluding,
      whereas 3h-daily maternal separations during SHRP increased rat's susceptibility
      to experimental panic attacks, separations throughout lactation had no effects on
      panic and enhanced active coping.

PMID- 29466714
TI  - Cell wall enrichment unveils proteomic changes in the cell wall during treatment
      of Mycobacterium smegmatis with sub-lethal concentrations of rifampicin.
AB  - : Understanding the cell wall of mycobacteria is crucial for improving drug
      design or identifying new antigens suitable to vaccination. Yet this remains
      problematic due to the complexity of the cell wall composition. In this study, we
      successfully developed gel-free approaches to study cell wall proteins in
      Mycobacterium smegmatis. The cell wall was subjected to differential
      centrifugation, differential detergent solubilisation and phase separation to
      yield the genuine cell wall proteome. Next, protein extracts were digested by
      filter-assisted sample preparation for LC-MS/MS analysis on a Q Exactive mass
      spectrometer, and identified proteins filtered through a stringent bioinformatics
      pipeline. This yielded the unprecedented coverage of 96 lipoproteins, 475
      membrane proteins and 73 secreted proteins. Employing this approach, we next
      quantified changes in the cell wall proteome during exposure of M. smegmatis to
      sub-lethal concentration of rifampicin. This facilitated detailed
      characterisation of the dysregulation of ABC transporters, virulence factors such
      as Mce proteins and PknG, and proteins involved in cell wall and lipid synthesis.
      Crucially, these cell wall proteins are under-represented in previous proteome
      analysis of M. smegmatis. This approach enables further quantitative proteomic
      studies of the role of the cell wall proteome of mycobacteria in virulence or
      during drug exposure. SIGNIFICANCE: We developed novel gel-free sample
      preparation workflows for the cell wall fraction of mycobacteria that
      significantly increase the coverage of the cell wall proteome compared to
      previous studies. We then provide a data analysis workflow that enables the
      removal of likely cytosolic contaminants in the cell wall fraction post
      measurement. Combined, these approaches increase the coverage of the cell wall
      proteome while ensuring that the identified proteins are true cell wall proteins
      and not carry-over of high-abundance contaminants from the cytosol. We have
      applied these approaches to quantify the dysregulation of cell wall proteins
      during exposure of M. smegmatis to rifampicin, which has shed new light on the
      coordinated down-regulation of ABC transporters as well as virulence factors
      present in the cell wall proteome.

PMID- 29466715
TI  - Ovine liver proteome: Assessing mechanisms of seasonal weight loss tolerance
      between Merino and Damara sheep.
AB  - : The effect of feed restriction on the liver protein profiles of two different
      breeds of sheep was studied. We compared Merino with the Damara, breeds with
      respectively low and high tolerance to nutritional stress. Each breed was grouped
      into two nutritional treatments: restricted (12-14% loss of live weight) and
      control (maintenance). The trial lasted 42 days. Animals were sacrificed and
      liver samples subjected to label free shotgun proteomics. The resultant proteins
      had both their fold change and statistical significance in an unpaired t-test
      calculated to identify differential protein abundance. The tool WebGestalt was
      utilized to perform an Overrepresentation Enrichment Analysis (ORA) for gene
      ontology terms associated with the significant proteins. We further validated
      shotgun proteomics findings using a selected reaction monitoring (SRM)-based
      targeted proteomics approach, where similar trends in regulation were obtained
      for a subset of relevant proteins across an independent cohort of animals.
      Results confirm that Damara has adapted to nutritional stress by mobilizing
      stored fatty acids within adipose tissue and converting them to energy more
      efficiently than Merino. Finally, Merino had an overabundance pattern primarily
      directed to protein synthesis pathways. Regulated proteins identified may be used
      as a basis for marker selection towards tolerance to nutritional stress.
      BIOLOGICAL SIGNIFICANCE: Sheep are one of the most important livestock animals.
      They remain however poorly understudied and described. Seasonal weight loss (SWL)
      due to pasture scarcity during the dry season is one of the most limiting
      conditions to ruminant production in the tropics. To counter SWL, farmers may use
      supplementation, expensive or difficult to implement. A more suitable long-term
      solution would be to use breeds that are naturally adapted to nutritional stress.
      This work contrasts two breeds with different levels of tolerance to SWL, the
      Damara and the Merino, respectively well and poorly adapted. Comparison is
      conducted at the level of the hepatic tissue and using label free proteomics.
      This work identifies a series of pathways in the liver of the Damara via label
      free proteomics that suggest a unique fatty acid metabolic process within this
      breed. Proteins that have increased abundance in the Damara in association with
      fatty acid metabolism may be used as potential markers of tolerance to
      nutritional stress. This research will pave the way for more viable, long-term
      solutions for farmers facing annual production problems due to drought in the
      tropics and the Mediterranean region.

PMID- 29466716
TI  - Characterization and risk assessment of seasonal and weather dynamics in organic
      pollutant mixtures from discharge of a separate sewer system.
AB  - Sites of wastewater discharge are hotspots for pollution of freshwaters with
      organic micropollutants and are often associated with adverse effects to aquatic
      organisms. The assessment, monitoring and managment of these hotspots is
      challenged by variations in the pollutant mixture composition due to season,
      weather conditions and random spills. In this study, we unraveled temporal
      exposure patterns in organic micropollutant mixtures from wastewater discharge
      and analyzed respective acute and sublethal risks for aquatic organisms. Samples
      were taken from two components of a separate sewer system i) a wastewater
      treatment plant (WWTP) and ii) a rain sewer of a medium size town as well as from
      the receiving river in different seasons. Rain sewer samples were separately
      collected for rain and dry - weather conditions. We analyzed 149 compounds by
      liquid chromatography-tandem mass spectrometry (LC-MS/MS). By considering the
      pollution dynamics in the point sources, we reduced the complexity of pollutant
      mixtures by k-means clustering to a few emission groups representing temporal and
      weather-related pollution patterns. From these groups, we derived biological
      quality element (BQE) - specific risk patterns. In most cases, one main risk
      driving emission group and a few individual risk driving compounds were
      identified for each BQE. While acute risk for fish was quite low, algae were
      exposed to seasonally emitted herbicides (terbuthylazine, spiroxamine) and
      crustaceans to randomly spilled insecticides (diazinon, dimethoate). Sublethal
      risks for all BQE were strongly influenced by constantly emitted pollutants,
      above all, pharmaceuticals. Variability of risks in the river was mainly driven
      by water discharge of the river rather than by season or peak events. Overall,
      the studied WWTP represented the major pollution source with a specific emission
      of agricultural compounds. However, the investigated rain sewer showed to be a
      constant pollution source due to illicit connections and was an important entry
      route for high loads of insecticides and biocides due to spills or incorrect
      disposal. By considering these pollution and risk dynamics, monitoring strategies
      may be optimized with a special focus on times of low flow conditions in the
      river, rain events and seasonally emitted risk drivers.

PMID- 29466717
TI  - Is bigger better? Driving factors of POTW performance in New York.
AB  - Like many regions around the world, New York State, USA, faces challenges in
      meeting wastewater treatment quality standards because of aging infrastructure,
      limited funding, shifting demographics and increasingly stringent environmental
      regulations. In recent decades construction of new wastewater treatment and
      distribution infrastructure in NY has most often occurred in exurban communities
      and suburban developments that are less dense than traditional urban cores. Here,
      we examine the role of size and capacity utilization on wastewater treatment
      effectiveness with respect to critical effluent parameters, and additionally
      explore which common facility engineering controls influence water quality
      treatment using a unique dataset of descriptive information. Our results
      challenge conventional wisdom, suggesting that the largest facilities (>30,000
      m3/d), not the smallest (<300 m3/d), discharge TSS, BOD, and coliform at
      significantly higher relative effluent concentrations (i.e., the ratio of
      discharged concentrations to allowable limits). Capacity utilization was also
      positively correlated to higher concentrations of TSS, BOD, and coliform effluent
      concentrations in larger facilities, though those concentrations were often
      within regulated limits. This implies that smaller-sized facilities may perform
      better in terms of environmental quality, but that the largest facilities
      demonstrate efficiency in the sense that they are not "over-treating" wastewater
      while avoiding violations. Results from NY suggest that medium sized facilities
      (300-30,000 m3/d) are sophisticated enough to incorporate appropriate unit
      processes, and employ operators with sufficient training and oversight, to reach
      treatment outcomes that are both reliable and of high quality.

PMID- 29466718
TI  - The impact of dissolved oxygen on sulfate radical-induced oxidation of organic
      micro-pollutants: A theoretical study.
AB  - Sulfate radical (SO4.-)-induced oxidation is an important technology in advanced
      oxidation processes (AOPs) for the removal of pollutants. To date, few studies
      have assessed the effects of dissolved oxygen (DO) on the SO4.--induced oxidation
      of organic micro-pollutants. In the present work, a quantum chemical calculation
      was used to investigate the influence of the external oxygen molecule on the
      Gibbs free energy (Gpollutant) and HOMO-LUMO gap (DeltaE) of 15 organic micro
      pollutants representing four chemical categories. Several thermodynamic and
      statistical models were combined with the data from the quantum chemical
      calculation to illustrate the impact of DO on the oxidation of organic micro
      pollutants by SO4.-. Results indicated that the external oxygen molecule
      increased Gpollutant of all studied chemicals, which implies DO has the potential
      to decrease the energy barrier of the SO4.--induced oxidation and shift the
      chemical equilibrium of the reaction towards the side of products. From the
      perspective of kinetics, DO can accelerate the oxidation by decreasing DeltaE of
      organic micro-pollutants. In addition, changes of Gpollutant and DeltaE of the
      SO4.--induced oxidation were both significantly different between open-chain and
      aromatic chemicals, and these differences were partially attributed to the
      difference of polarizability of these two types of chemicals. Furthermore, we
      revealed that all changes of Gpollutant and DeltaE induced by DO were dependent
      on the DO content. Our study emphasizes the significance of DO on the oxidation
      of organic micro-pollutants by SO4.-, and also provides a theoretical method to
      study the effect of components in wastewater on removal of organic pollutants in
      AOPs.

PMID- 29466719
TI  - Simultaneous odour-face presentation strengthens hedonic evaluations and event
      related potential responses influenced by unpleasant odour.
AB  - Odours alter evaluations of concurrently presented visual stimuli, such as faces.
      Stimulus onset asynchrony (SOA) is known to affect evaluative priming in various
      sensory modalities. However, effects of SOA on odour priming of visual stimuli
      are not known. The present study aimed to analyse whether subjective and cortical
      activation changes during odour priming would vary as a function of SOA between
      odours and faces. Twenty-eight participants rated faces under pleasant,
      unpleasant, and no-odour conditions using visual analogue scales. In half of
      trials, faces appeared one-second after odour offset (SOA 1). In the other half
      of trials, faces appeared during the odour pulse (SOA 2). EEG was recorded
      continuously using a 128-channel system, and event-related potentials (ERPs) to
      face stimuli were evaluated using statistical parametric mapping (SPM). Faces
      presented during unpleasant-odour stimulation were rated significantly less
      pleasant than the same faces presented one-second after offset of the unpleasant
      odour. Scalp-time clusters in the late-positive-potential (LPP) time-range showed
      an interaction between odour and SOA effects, whereby activation was stronger for
      faces presented simultaneously with the unpleasant odour, compared to the same
      faces presented after odour offset. Our results highlight stronger unpleasant
      odour priming with simultaneous, compared to delayed, odour-face presentation.
      Such effects were represented in both behavioural and neural data. A greater
      cortical and subjective response during simultaneous presentation of faces and
      unpleasant odour may have an adaptive role, allowing for a prompt and focused
      behavioural reaction to a concurrent stimulus if an aversive odour would signal
      danger, or unwanted social interaction.

PMID- 29466720
TI  - Modulation of corticospinal excitability during positive and negative motor
      imageries.
AB  - We investigated corticospinal excitability during positive (execution) and
      negative (suppression) imageries for the right and left upper and lower limbs. In
      the Positive Imagery tasks, sixteen subjects were instructed to repeatedly
      imagine rotation of the index finger of the right or left hand, or the ankle of
      the right or left foot. In the Negative Imagery tasks, they were asked to imagine
      the suppression of movements for the index finger of the right or left hand, or
      the ankle of the right or left foot. A single-pulse transcranial magnetic
      stimulation was delivered over the left hand primary motor cortex, and motor
      evoked potentials (MEPs) were recorded from the right first dorsal interosseous
      (FDI) muscle under all conditions. The MEP amplitudes of the FDI were
      significantly larger in the Positive and Negative Imagery tasks than in the
      resting control task during motor imagery of the right hand, left hand, and left
      foot, but not during that of right foot. Our results indicate that imageries of
      suppressing hand and foot movements enhanced corticospinal excitability.

PMID- 29466721
TI  - Insights from molecular dynamics simulations to exploit new trends for the
      development of improved opioid drugs.
AB  - Having accidental deaths from opioid overdoses almost quadrupled over the past
      fifteen years, there is a strong need to develop new, non-addictive medications
      for chronic pain to stop one of the deadliest epidemics in American history.
      Given their potentially fewer on-target overdosing risks and other adverse
      effects compared to classical opioid drugs, attention has recently shifted to
      opioid allosteric modulators and G protein-biased opioid agonists as likely drug
      candidates to prevent and/or reverse opioid overdoses. Understanding how these
      molecules bind and activate their receptors at an atomistic level is key to
      developing them into effective new therapeutics, and molecular dynamics-based
      strategies are contributing tremendously to this understanding.

PMID- 29466722
TI  - Shared and distinct regional homogeneity changes in bipolar and unipolar
      depression.
AB  - BACKGROUND: Bipolar depression (BD) is easily misdiagnosed as unipolar depression
      (UD) or major depressive disorder (MDD) because the depressive symptoms can
      overlap. Regional homogeneity (ReHo), a measure commonly used for analyzing
      resting-state fMRI data, has been applied to the study of various
      neuropsychiatric disorders. However, to date, studies directly comparing BD and
      UD using ReHo have been relatively scarce. Further investigation is needed to
      study the latent pathophysiological mechanisms of BD and UD. METHODS: Fifty-five
      patients with BD and 76 patients with UD, as well as 113 healthy controls (HC),
      underwent resting-state functional magnetic resonance imaging (fMRI). We compared
      the voxel-wise ReHo across the whole brain for subjects in each of the three
      groups. RESULTS: Significant differences were found in the left frontal cluster
      (LFC) across the three groups. There were differences between BD and UD in the
      LFC and left temporal cluster (LTC). In addition, differences between UD and HC
      existed in the LFC and the occipital cluster (OC). When comparing BD subjects
      with HC subjects, significant differences were found in all three clusters. No
      correlations were observed between the 17-item Hamilton Depression Rating Scale
      (HDRS-17) scores or sub-scores and the ReHo values of BD or UD patients.
      CONCLUSION: ReHo values in the LFC differed significantly among BD, UD, and HC
      subjects. ReHo in the LTC showed significant differences between BD and UD that
      might serve as neuroimaging markers of BD. Further, BD and UD shared ReHo changes
      in the cuneus, suggesting that the cuneus might provide a depressive state
      neuroimaging marker of BD and UD patients.

PMID- 29466723
TI  - Small-Molecule Screen Identifies De Novo Nucleotide Synthesis as a Vulnerability
      of Cells Lacking SIRT3.
AB  - Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase downregulated in aging and age
      associated diseases such as cancer and neurodegeneration and in high-fat diet
      (HFD)-induced metabolic disorders. Here, we performed a small-molecule screen and
      identified an unexpected metabolic vulnerability associated with SIRT3 loss.
      Azaserine, a glutamine analog, was the top compound that inhibited growth and
      proliferation of cells lacking SIRT3. Using stable isotope tracing of glutamine,
      we observed its increased incorporation into de novo nucleotide synthesis in
      SIRT3 knockout (KO) cells. Furthermore, we found that SIRT3 KO cells upregulated
      the diversion of glutamine into de novo nucleotide synthesis through hyperactive
      mTORC1 signaling. Overexpression of SIRT3 suppressed mTORC1 and growth in vivo in
      a xenograft tumor model of breast cancer. Thus, we have uncovered a metabolic
      vulnerability of cells with SIRT3 loss by using an unbiased small-molecule
      screen.

PMID- 29466724
TI  - BK Potassium Channels Suppress Cavalpha2delta Subunit Function to Reduce
      Inflammatory and Neuropathic Pain.
AB  - Cavalpha2delta subunits contribute to the cell-surface expression of Cav2 calcium
      channels. Upregulation of Cavalpha2delta-1 in dorsal root ganglion neurons occurs
      after nerve injury and results in an increased synaptic abundance of Cav2.2
      channels in the spinal dorsal horn, thus enhancing the transmission of pain
      signals. Here, we report that large conductance calcium-activated potassium (BK)
      channels interact with the Cavalpha2delta subunit. Coexpression of BK channels
      with the Cav2 calcium channels reduces their cell-surface expression and whole
      cell current density by competing the Cavalpha2delta subunit away from the Cav2
      complex. Biochemical analysis reveals that the extracellular N terminus region of
      the BK channel is the key molecular determinant of this effect. Intrathecally
      delivered virus constructs encoding a membrane-anchored BK channel N terminus
      peptide produces long-lasting analgesia in mouse models of inflammatory and
      neuropathic pain. Collectively, our data reveal an endogenous ligand of the
      Cavalpha2delta subunit with analgesic properties.

PMID- 29466725
TI  - Munc13-3 Is Required for the Developmental Localization of Ca2+ Channels to
      Active Zones and the Nanopositioning of Cav2.1 Near Release Sensors.
AB  - Spatial relationships between Cav channels and release sensors at active zones
      (AZs) are a major determinant of synaptic fidelity. They are regulated
      developmentally, but the underlying molecular mechanisms are largely unclear.
      Here, we show that Munc13-3 regulates the density of Cav2.1 and Cav2.2 channels,
      alters the localization of Cav2.1, and is required for the development of tight,
      nanodomain coupling at parallel-fiber AZs. We combined EGTA application and Ca2+
      channel pharmacology in electrophysiological and two-photon Ca2+ imaging
      experiments with quantitative freeze-fracture immunoelectron microscopy and
      mathematical modeling. We found that a normally occurring developmental shift
      from release being dominated by Ca2+ influx through Cav2.1 and Cav2.2 channels
      with domain overlap and loose coupling (microdomains) to a nanodomain Cav2.1 to
      sensor coupling is impaired in Munc13-3-deficient synapses. Thus, at AZs lacking
      Munc13-3, release remained triggered by Cav2.1 and Cav2.2 microdomains,
      suggesting a critical role of Munc13-3 in the formation of release sites with
      calcium channel nanodomains.

PMID- 29466726
TI  - Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in
      the Adult Mouse Brain.
AB  - Restoring adult stem cell function provides an exciting approach for rejuvenating
      the aging brain. However, molecular mechanisms mediating neurogenic rejuvenation
      remain elusive. Here we report that the enzyme ten eleven translocation
      methylcytosine dioxygenase 2 (Tet2), which catalyzes the production of 5
      hydroxymethylcytosine (5hmC), rescues age-related decline in adult neurogenesis
      and enhances cognition in mice. We detected a decrease in Tet2 expression and
      5hmC levels in the aged hippocampus associated with adult neurogenesis. Mimicking
      an aged condition in young adults by abrogating Tet2 expression within the
      hippocampal neurogenic niche, or adult neural stem cells, decreased neurogenesis
      and impaired learning and memory. In a heterochronic parabiosis rejuvenation
      model, hippocampal Tet2 expression was restored. Overexpressing Tet2 in the
      hippocampal neurogenic niche of mature adults increased 5hmC associated with
      neurogenic processes, offset the precipitous age-related decline in neurogenesis,
      and enhanced learning and memory. Our data identify Tet2 as a key molecular
      mediator of neurogenic rejuvenation.

PMID- 29466727
TI  - In Vivo Analysis of Centromeric Proteins Reveals a Stem Cell-Specific Asymmetry
      and an Essential Role in Differentiated, Non-proliferating Cells.
AB  - Stem cells of the Drosophila midgut (ISCs) are the only mitotically dividing
      cells of the epithelium and, therefore, presumably the only epithelial cells that
      require functional kinetochores for microtubule spindle attachment during
      mitosis. The histone variant CENP-A marks centromeric chromatin as the site of
      kinetochore formation and spindle attachment during mitotic chromosome
      segregation. Here, we show that centromeric proteins distribute asymmetrically
      during ISC division. Whereas newly synthesized CENP-A is enriched in
      differentiating progeny, CENP-C is undetectable in these cells. Remarkably, CENP
      A persists in ISCs for weeks without being replaced, consistent with it being an
      epigenetic mark responsible for maintaining stem cell properties. Furthermore,
      CENP-A and its loading factor CAL1 were found to be essential for post-mitotic,
      differentiating cells; removal of any of these factors interferes with
      endoreduplication. Taken together, we propose two additional roles of CENP-A: to
      maintain stem cell-unique properties and to regulate post-mitotic cells.

PMID- 29466728
TI  - LKB1 as a Gatekeeper of Hepatocyte Proliferation and Genomic Integrity during
      Liver Regeneration.
AB  - Liver kinase B1 (LKB1) is involved in several biological processes and is a key
      regulator of hepatic metabolism and polarity. Here, we demonstrate that the
      master kinase LKB1 plays a dual role in liver regeneration, independently of its
      major target, AMP-activated protein kinase (AMPK). We found that the loss of
      hepatic Lkb1 expression promoted hepatocyte proliferation acceleration
      independently of metabolic/energetic balance. LKB1 regulates G0/G1 progression,
      specifically by controlling epidermal growth factor receptor (EGFR) signaling.
      Furthermore, later in regeneration, LKB1 controls mitotic fidelity. The deletion
      of Lkb1 results in major alterations to mitotic spindle formation along the
      polarity axis. Thus, LKB1 deficiency alters ploidy profile at late stages of
      regeneration. Our findings highlight the dual role of LKB1 in liver regeneration,
      as a guardian of hepatocyte proliferation and genomic integrity.

PMID- 29466729
TI  - A Cell-Intrinsic Interferon-like Response Links Replication Stress to Cellular
      Aging Caused by Progerin.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused
      by a truncated lamin A protein (progerin) that drives cellular and organismal
      decline. HGPS patient-derived fibroblasts accumulate genomic instability, but its
      underlying mechanisms and contribution to disease remain poorly understood. Here,
      we show that progerin-induced replication stress (RS) drives genomic instability
      by eliciting replication fork (RF) stalling and nuclease-mediated degradation.
      Rampant RS is accompanied by upregulation of the cGAS/STING cytosolic DNA sensing
      pathway and activation of a robust STAT1-regulated interferon (IFN)-like
      response. Reducing RS and the IFN-like response, especially with calcitriol,
      improves the fitness of progeria cells and increases the efficiency of cellular
      reprogramming. Importantly, other compounds that improve HGPS phenotypes reduce
      RS and the IFN-like response. Our study reveals mechanisms underlying progerin
      toxicity, including RS-induced genomic instability and activation of IFN-like
      responses, and their relevance for cellular decline in HGPS.

PMID- 29466730
TI  - A LIN28B Tumor-Specific Transcript in Cancer.
AB  - The diversity and complexity of the cancer transcriptome may contain transcripts
      unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST,
      which is specifically expressed in hepatocellular carcinoma (HCC) and many other
      cancer types. Expression of LIN28B-TST is associated with significantly poor
      prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative
      transcription initiation site that harbors a strong promoter regulated by NFYA
      but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite
      for its transcription and transcriptional regulation. LIN28B-TST encodes a
      protein isoform with additional N-terminal amino acids and is critical for cancer
      cell proliferation and tumorigenesis. Our findings reveal a mechanism of LIN28B
      activation in cancer and the potential utility of LIN28B-TST for clinical
      purposes.

PMID- 29466731
TI  - Spine Patterning Is Guided by Segmentation of the Notochord Sheath.
AB  - The spine is a segmented axial structure made of alternating vertebral bodies
      (centra) and intervertebral discs (IVDs) assembled around the notochord. Here, we
      show that, prior to centra formation, the outer epithelial cell layer of the
      zebrafish notochord, the sheath, segments into alternating domains corresponding
      to the prospective centra and IVD areas. This process occurs sequentially in an
      anteroposterior direction via the activation of Notch signaling in alternating
      segments of the sheath, which transition from cartilaginous to mineralizing
      domains. Subsequently, osteoblasts are recruited to the mineralized domains of
      the notochord sheath to form mature centra. Tissue-specific manipulation of Notch
      signaling in sheath cells produces notochord segmentation defects that are
      mirrored in the spine. Together, our findings demonstrate that notochord sheath
      segmentation provides a template for vertebral patterning in the zebrafish spine.

PMID- 29466733
TI  - Abeta Facilitates LTD at Schaffer Collateral Synapses Preferentially in the Left
      Hippocampus.
AB  - Promotion of long-term depression (LTD) mechanisms by synaptotoxic soluble
      oligomers of amyloid-beta (Abeta) has been proposed to underlie synaptic
      dysfunction in Alzheimer's disease (AD). Previously, LTD was induced by
      relatively non-specific electrical stimulation. Exploiting optogenetics, we
      studied LTD using a more physiologically diffuse spatial pattern of selective
      pathway activation in the rat hippocampus in vivo. This relatively sparse
      synaptic LTD requires both the ion channel function and GluN2B subunit of the
      NMDA receptor but, in contrast to electrically induced LTD, is not facilitated by
      boosting endogenous muscarinic acetylcholine or metabotropic glutamate 5 receptor
      activation. Although in the absence of Abeta, there is no evidence of hippocampal
      LTD asymmetry, in the presence of Abeta, the induction of LTD is preferentially
      enhanced in the left hippocampus in an mGluR5-dependent manner. This circuit
      selective disruption of synaptic plasticity by Abeta provides a route to
      understanding the development of aberrant brain lateralization in AD.

PMID- 29466732
TI  - Dissonant Representations of Visual Space in Prefrontal Cortex during Eye
      Movements.
AB  - We used local field potentials (LFPs) and spikes to investigate representations
      of visual space in prefrontal cortex and the dynamics of those representations
      during eye movements. Spatial information contained in LFPs of the frontal eye
      field (FEF) was differentially distributed across frequencies, with a majority of
      that information being carried in alpha and high-gamma bands and minimal signal
      in the low-gamma band. During fixation, spatial information from alpha and high
      gamma bands and spiking activity was robust across cortical layers. Receptive
      fields (RFs) derived from alpha and high-gamma bands were retinocentrically
      organized, and they were spatially correlated both with each other and with
      spiking RFs. However, alpha and high-gamma RFs probed before eye movements were
      dissociated. Whereas high-gamma and spiking RFs immediately converged toward the
      movement goal, alpha RFs remained largely unchanged during the initial probe
      response, but they converged later. These observations reveal possible mechanisms
      of dynamic spatial representations that underlie visual perception during eye
      movements.

PMID- 29466734
TI  - Pharmacological Inhibition of Necroptosis Protects from Dopaminergic Neuronal
      Cell Death in Parkinson's Disease Models.
AB  - Dysfunctions in mitochondrial dynamics and metabolism are common pathological
      processes associated with Parkinson's disease (PD). It was recently shown that an
      inherited form of PD and dementia is caused by mutations in the OPA1 gene, which
      encodes for a key player in mitochondrial fusion and structure. iPSC-derived
      neural cells from these patients exhibited severe mitochondrial fragmentation,
      respiration impairment, ATP deficits, and heightened oxidative stress.
      Reconstitution of normal levels of OPA1 in PD-derived neural cells normalized
      mitochondria morphology and function. OPA1-mutated neuronal cultures showed
      reduced survival in vitro. Intriguingly, selective inhibition of necroptosis
      effectively rescued this survival deficit. Additionally, dampening necroptosis in
      MPTP-treated mice protected from DA neuronal cell loss. This human iPSC-based
      model captures both early pathological events in OPA1 mutant neural cells and the
      beneficial effects of blocking necroptosis, highlighting this cell death process
      as a potential therapeutic target for PD.

PMID- 29466735
TI  - Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy.
AB  - Microglia are well known to play a critical role in maintaining brain
      homeostasis. However, their role in epileptogenesis has yet to be determined.
      Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to
      phenotypic changes, including an amoeboid-like morphology, increased
      proliferation, and robust phagocytosis activity, but without a significant
      induction of pro-inflammatory cytokines. We further provide evidence that these
      noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to
      reduced synapse density, marked microglial infiltration into hippocampal
      pyramidal layers, moderate neuronal degeneration, and massive proliferation of
      astrocytes. Moreover, the mice thus affected develop severe early-onset
      spontaneous recurrent seizures (SRSs). Therefore, we have revealed an
      epileptogenic mechanism that is independent of the microglial inflammatory
      response. Our data suggest that microglia could be an opportune target for
      epilepsy prevention.

PMID- 29466737
TI  - Suppression of Tcf1 by Inflammatory Cytokines Facilitates Effector CD8 T Cell
      Differentiation.
AB  - The formation of central CD8 T cell memory in response to infection depends on
      the transcription factor Tcf1 (Tcf7). Tcf1 is expressed at high levels in naive
      CD8 T cells but downregulated in most CD8 T cells during effector
      differentiation. The relevance of Tcf1 downregulation for effector
      differentiation and the signals controlling Tcf1 expression have not been
      elucidated. Here, we show that systemic inflammatory signals downregulated Tcf1
      in CD8 T cells during dendritic cell vaccination and bacterial infections. The
      suppressive effect was mediated by the inflammatory cytokine interleukin 12 (IL
      12), which acted via STAT4 in CD8 T cells. IL-12-induced Tcf1 downregulation
      required cell cycling, occurred at the transcriptional level, and was prevented
      in part by inhibiting DNA methyltransferases. Absence of Tcf1 during T cell
      priming circumvented the need of systemic inflammation for effector
      differentiation. We conclude that silencing of Tcf1 by systemic inflammation
      facilitates effector CD8 T cell differentiation.

PMID- 29466736
TI  - Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human
      Induced Regulatory T Cells.
AB  - Regulatory T (Treg) cells are critical in regulating the immune response. In
      vitro induced Treg (iTreg) cells have significant potential in clinical medicine.
      However, applying iTreg cells as therapeutics is complicated by the poor
      stability of human iTreg cells and their variable suppressive activity.
      Therefore, it is important to understand the molecular mechanisms of human iTreg
      cell specification. We identified hypermethylated in cancer 1 (HIC1) as a
      transcription factor upregulated early during the differentiation of human iTreg
      cells. Although FOXP3 expression was unaffected, HIC1 deficiency led to a
      considerable loss of suppression by iTreg cells with a concomitant increase in
      the expression of effector T cell associated genes. SNPs linked to several immune
      mediated disorders were enriched around HIC1 binding sites, and in vitro binding
      assays indicated that these SNPs may alter the binding of HIC1. Our results
      suggest that HIC1 is an important contributor to iTreg cell development and
      function.

PMID- 29466738
TI  - Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1
      Mediated mRNA Stabilization of Cyclin D1 and Tmem176b.
AB  - Circadian rhythms regulate cell proliferation and differentiation; however,
      little is known about their roles in myogenic differentiation. Our synchronized
      differentiation studies demonstrate that myoblast proliferation and subsequent
      myotube formation by cell fusion occur in circadian manners. We found that one of
      the core regulators of circadian rhythms, Cry2, but not Cry1, is critical for the
      circadian patterns of these two critical steps in myogenic differentiation. This
      is achieved through the specific interaction between Cry2 and Bclaf1, which
      stabilizes mRNAs encoding cyclin D1, a G1/S phase transition regulator, and
      Tmem176b, a transmembrane regulator for myogenic cell fusion. Myoblasts lacking
      Cry2 display premature cell cycle exit and form short myotubes because of
      inefficient cell fusion. Consistently, muscle regeneration is impaired in Cry2-/-
      mice. Bclaf1 knockdown recapitulated the phenotypes of Cry2 knockdown: early cell
      cycle exit and inefficient cell fusion. This study uncovers a post
      transcriptional regulation of myogenic differentiation by circadian rhythms.

PMID- 29466740
TI  - TALEN-Induced Double-Strand Break Repair of CTG Trinucleotide Repeats.
AB  - Trinucleotide repeat expansions involving CTG/CAG triplets are responsible for
      several neurodegenerative disorders, including myotonic dystrophy and
      Huntington's disease. Because expansions trigger the disease, contracting repeat
      length could be a possible approach to gene therapy for these disorders. Here, we
      show that a TALEN-induced double-strand break was very efficient at contracting
      expanded CTG repeats in yeast. We show that RAD51, POL32, and DNL4 are
      dispensable for double-strand break repair within CTG repeats, the only required
      genes being RAD50, SAE2, and RAD52. Resection was totally abolished in the
      absence of RAD50 on both sides of the break, whereas it was reduced in a
      sae2Delta mutant on the side of the break containing the longest repeat tract,
      suggesting that secondary structures at double-strand break ends must be removed
      by the Mre11-Rad50 complex and Sae2. Following the TALEN double-strand break,
      single-strand annealing occurred between both sides of the repeat tract, leading
      to repeat contraction.

PMID- 29466739
TI  - Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue
      Expansion, and Promotes Obesity and Insulin Resistance.
AB  - While therapeutic modulation of miRNAs provides a promising approach for numerous
      diseases, the promiscuous nature of miRNAs raises concern over detrimental off
      target effects. miR-33 has emerged as a likely target for treatment of
      cardiovascular diseases. However, the deleterious effects of long-term anti-miR
      33 therapies and predisposition of miR-33-/- mice to obesity and metabolic
      dysfunction exemplify the possible pitfalls of miRNA-based therapies. Our work
      provides an in-depth characterization of miR-33-/- mice and explores the
      mechanisms by which loss of miR-33 promotes insulin resistance in key metabolic
      tissues. Contrary to previous reports, our data do not support a direct role for
      SREBP-1-mediated lipid synthesis in promoting these effects. Alternatively, in
      adipose tissue of miR-33-/- mice, we observe increased pre-adipocyte
      proliferation, enhanced lipid uptake, and impaired lipolysis. Moreover, we
      demonstrate that the driving force behind these abnormalities is increased food
      intake, which can be prevented by pair feeding with wild-type animals.

PMID- 29466741
TI  - Rap1 Negatively Regulates the Hippo Pathway to Polarize Directional Protrusions
      in Collective Cell Migration.
AB  - In collective cell migration, directional protrusions orient cells in response to
      external cues, which requires coordinated polarity among the migrating cohort.
      However, the molecular mechanism has not been well defined. Drosophila border
      cells (BCs) migrate collectively and invade via the confined space between nurse
      cells, offering an in vivo model to examine how group polarity is organized.
      Here, we show that the front/back polarity of BCs requires Rap1, hyperactivation
      of which disrupts cluster polarity and induces misoriented protrusions and loss
      of asymmetry in the actin network. Conversely, hypoactive Rap1 causes fewer
      protrusions and cluster spinning during migration. A forward genetic screen
      revealed that downregulation of the Hippo (Hpo) pathway core components hpo or
      mats enhances the Rap1V12-induced migration defect and misdirected protrusions.
      Mechanistically, association of Rap1V12 with the kinase domain of Hpo suppresses
      its activity, which releases Hpo signaling-mediated suppression of F-actin
      elongation, promoting cellular protrusions in collective cell migration.

PMID- 29466742
TI  - Compartment-Specific Biosensors Reveal a Complementary Subcellular Distribution
      of Bioactive Furin and PC7.
AB  - Furin trafficking, and that of related proprotein convertases (PCs), may regulate
      which substrates are accessible for endoproteolysis, but tools to directly test
      this hypothesis have been lacking. Here, we develop targeted biosensors that
      indicate Furin activity in endosomes is 10-fold less inhibited by decanoyl-RVKR
      chloromethylketone and enriched >3-fold in endosomes compared to the trans-Golgi
      network (TGN). Endogenous PC7, which resists this inhibitor, was active in
      distinct vesicles. Only overexpressed PC7 activity reached the cell surface,
      endosomes, and the TGN. A PLC motif in the cytosolic tail of PC7 was dispensable
      for endosomal activity, but it was specifically required for TGN recycling and to
      rescue proActivin-A cleavage in Furin-depleted B16F1 melanoma cells. In sharp
      contrast, PC7 complemented Furin in cleaving Notch1 independently of PLC-mediated
      TGN access. Our study provides a proof in principle that compartment-specific
      biosensors can be used to gain insight into the regulation of PC trafficking and
      to map the tropism of PC-specific inhibitors.

PMID- 29466744
TI  - Single-Cell Droplet Microfluidic Screening for Antibodies Specifically Binding to
      Target Cells.
AB  - Monoclonal antibodies are a main player in modern drug discovery. Many antibody
      screening formats exist, each with specific advantages and limitations.
      Nonetheless, it remains challenging to screen antibodies for the binding of cell
      surface receptors (the most important class of all drug targets) or for the
      binding to target cells rather than purified proteins. Here, we present a high
      throughput droplet microfluidics approach employing dual-color normalized
      fluorescence readout to detect antibody binding. This enables us to obtain
      quantitative data on target cell recognition, using as little as 33 fg of IgG per
      assay. Starting with an excess of hybridoma cells releasing unspecific
      antibodies, individual clones secreting specific binders (of target cells co
      encapsulated into droplets) could be enriched 220-fold after sorting 80,000
      clones in a single experiment. This opens the way for therapeutic antibody
      discovery, especially since the single-cell approach is in principle also
      applicable to primary human plasma cells.

PMID- 29466743
TI  - A Roadmap for Human Liver Differentiation from Pluripotent Stem Cells.
AB  - How are closely related lineages, including liver, pancreas, and intestines,
      diversified from a common endodermal origin? Here, we apply principles learned
      from developmental biology to rapidly reconstitute liver progenitors from human
      pluripotent stem cells (hPSCs). Mapping the formation of multiple endodermal
      lineages revealed how alternate endodermal fates (e.g., pancreas and intestines)
      are restricted during liver commitment. Human liver fate was encoded by
      combinations of inductive and repressive extracellular signals at different
      doses. However, these signaling combinations were temporally re-interpreted:
      cellular competence to respond to retinoid, WNT, TGF-beta, and other signals
      sharply changed within 24 hr. Consequently, temporally dynamic manipulation of
      extracellular signals was imperative to suppress the production of unwanted cell
      fates across six consecutive developmental junctures. This efficiently generated
      94.1% +/- 7.35% TBX3+HNF4A+ human liver bud progenitors and 81.5% +/- 3.2% FAH+
      hepatocyte-like cells by days 6 and 18 of hPSC differentiation, respectively; the
      latter improved short-term survival in the Fah-/-Rag2-/-Il2rg-/- mouse model of
      liver failure.

PMID- 29466746
TI  - T Cell LEGO: Identifying the Master Builders and What They Do.
AB  - Understanding how cell fate decisions are made during cellular differentiation
      and the mechanisms that drive them is a holy grail of cell biology. In this issue
      of Immunity, Hu et al. (2018) and Johnson et al. (2018) demonstrate that key
      transcriptional regulators and global changes in nuclear architecture underlie
      differentiation decisions during T cell development.

PMID- 29466745
TI  - Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord
      Neurons and Their Activity during Behavior.
AB  - To understand the cellular basis of behavior, it is necessary to know the cell
      types that exist in the nervous system and their contributions to function.
      Spinal networks are essential for sensory processing and motor behavior and
      provide a powerful system for identifying the cellular correlates of behavior.
      Here, we used massively parallel single nucleus RNA sequencing (snRNA-seq) to
      create an atlas of the adult mouse lumbar spinal cord. We identified and
      molecularly characterized 43 neuronal populations. Next, we leveraged the snRNA
      seq approach to provide unbiased identification of neuronal populations that were
      active following a sensory and a motor behavior, using a transcriptional
      signature of neuronal activity. This approach can be used in the future to link
      single nucleus gene expression data with dynamic biological responses to
      behavior, injury, and disease.

PMID- 29466747
TI  - Stem Cells Cycle toward Immune Surveillance.
AB  - Immune surveillance is an established regulatory mechanism that spares tissues
      from malignant transformation. Agudo et al. (2018) find that the chief cell type
      to generate tissues in the body-somatic stem cells-is subject to immune
      surveillance only during proliferation.

PMID- 29466748
TI  - Infants Harness the Germline against RSV.
AB  - In this issue of Immunity, Goodwin et al. (2018) offer hope for an RSV vaccine
      for young infants by demonstrating that RSV infection in very young infants
      induces neutralizing antibodies that are close to the germline and have unusual
      epitope specificity.

PMID- 29466749
TI  - A New Link between gammadelta T Cells and Myeloid Cells in Malaria?
AB  - In malaria, the immune responses leading to protective immunity versus
      immunopathology are unclear. Mamedov et al. (2018) identify a subset of clonally
      expanded gammadelta T cells in late-stage infection that produce M-CSF and may
      interact with myeloid cells to control recrudescent infection.

PMID- 29466750
TI  - Microglia: You'll Never Walk Alone!
AB  - In this issue of Immunity, Mrdjen et al. (2018) use high-dimensional single-cell
      proteomics and high parametric mass cytometry to provide insight into the long
      lasting issue of how to identify and characterize both resident and recruited
      leukocyte populations in healthy, aged, and diseased CNS.

PMID- 29466751
TI  - NKTeeing Up B Cell Responses to Viral Infection.
AB  - Activated B cells mature in germinal centers (GCs), but GC initiation during
      infection is poorly understood. Gaya et al. (2018) show that NKT cells, activated
      by CD169+ macrophages, produce an early wave of interleukin-4 (IL-4) that
      promotes GC formation during viral infection.

PMID- 29466752
TI  - Have Cytokines, Will Travel.
AB  - In many contexts, innate lymphoid cells (ILCs) are primarily tissue resident. By
      contrast, in a recent issue of Science, Huang et al. (2018) show that
      inflammatory type 2 ILCs migrate from the intestine to the lungs and that this
      movement is guided by sphingosine-1-phosphate receptors.

PMID- 29466753
TI  - Human T Cell Development, Localization, and Function throughout Life.
AB  - Throughout life, T cells coordinate multiple aspects of adaptive immunity,
      including responses to pathogens, allergens, and tumors. In mouse models, the
      role of T cells is studied in the context of a specific type of pathogen,
      antigen, or disease condition over a limited time frame, whereas in humans, T
      cells control multiple insults simultaneously throughout the body and maintain
      immune homeostasis over decades. In this review, we discuss how human T cells
      develop and provide essential immune protection at different life stages and
      highlight tissue localization and subset delineation as key determinants of the T
      cell functional role in immune responses. We also discuss how anatomic
      compartments undergo distinct age-associated changes in T cell subset composition
      and function over a lifetime. It is important to consider age and tissue
      influences on human T cells when developing targeted strategies to modulate T
      cell-mediated immunity in vaccines and immunotherapies.

PMID- 29466754
TI  - Understanding Subset Diversity in T Cell Memory.
AB  - Considerable advances have been made in recent years in understanding the
      generation and function of memory T cells. Memory T cells are typically parsed
      into discreet subsets based on phenotypic definitions that connote distinct roles
      in immunity. Here we consider new developments in the field and focus on how
      emerging differences between memory cells with respect to their trafficking,
      metabolism, epigenetic regulation, and longevity may fail to fit into small
      groups of "memory subsets." Rather, the properties of individual memory T cells
      fall on a continuum within each of these and other parameters. We discuss how
      this continuum influences the way that the efficacy of vaccination is assessed,
      as well as the suitability of a memory population for protective immunity.

PMID- 29466755
TI  - Transformation of Accessible Chromatin and 3D Nucleome Underlies Lineage
      Commitment of Early T Cells.
AB  - How chromatin reorganization coordinates differentiation and lineage commitment
      from hematopoietic stem and progenitor cells (HSPCs) to mature immune cells has
      not been well understood. Here, we carried out an integrative analysis of
      chromatin accessibility, topologically associating domains, AB compartments, and
      gene expression from HSPCs to CD4+CD8+ T cells. We found that abrupt genome-wide
      changes at all three levels of chromatin organization occur during the transition
      from double-negative stage 2 (DN2) to DN3, accompanying the T lineage commitment.
      The transcription factor BCL11B, a critical regulator of T cell commitment, is
      associated with increased chromatin interaction, and Bcl11b deletion compromised
      chromatin interaction at its target genes. We propose that these large-scale and
      concerted changes in chromatin organization present an energy barrier to prevent
      the cell from reversing its fate to earlier stages or redirecting to alternatives
      and thus lock the cell fate into the T lineages.

PMID- 29466756
TI  - Lineage-Determining Transcription Factor TCF-1 Initiates the Epigenetic Identity
      of T Cells.
AB  - T cell development is orchestrated by transcription factors that regulate the
      expression of genes initially buried within inaccessible chromatin, but the
      transcription factors that establish the regulatory landscape of the T cell
      lineage remain unknown. Profiling chromatin accessibility at eight stages of T
      cell development revealed the selective enrichment of TCF-1 at genomic regions
      that became accessible at the earliest stages of development. TCF-1 was further
      required for the accessibility of these regulatory elements and at the single
      cell level, it dictated a coordinate opening of chromatin in T cells. TCF-1
      expression in fibroblasts generated de novo chromatin accessibility even at
      chromatin regions with repressive marks, inducing the expression of T cell
      restricted genes. These results indicate that a mechanism by which TCF-1 controls
      T cell fate is through its widespread ability to target silent chromatin and
      establish the epigenetic identity of T cells.

PMID- 29466757
TI  - Quiescent Tissue Stem Cells Evade Immune Surveillance.
AB  - Stem cells are critical for the maintenance of many tissues, but whether their
      integrity is maintained in the face of immunity is unclear. Here we found that
      cycling epithelial stem cells, including Lgr5+ intestinal stem cells, as well as
      ovary and mammary stem cells, were eliminated by activated T cells, but quiescent
      stem cells in the hair follicle and muscle were resistant to T cell killing.
      Immune evasion was an intrinsic property of the quiescent stem cells resulting
      from systemic downregulation of the antigen presentation machinery, including MHC
      class I and TAP proteins, and is mediated by the transactivator NLRC5. This
      process was reversed upon stem cell entry into the cell cycle. These studies
      identify a link between stem cell quiescence, antigen presentation, and immune
      evasion. As cancer-initiating cells can derive from stem cells, these findings
      may help explain how the earliest cancer cells evade immune surveillance.

PMID- 29466758
TI  - T Cells in Nonlymphoid Tissues Give Rise to Lymph-Node-Resident Memory T Cells.
AB  - Immunosurveillance of secondary lymphoid organs (SLO) is performed by central
      memory T cells that recirculate through blood. Resident memory T (Trm) cells
      remain parked in nonlymphoid tissues and often stably express CD69. We recently
      identified Trm cells within SLO, but the origin and phenotype of these cells
      remains unclear. Using parabiosis of "dirty" mice, we found that CD69 expression
      is insufficient to infer stable residence of SLO Trm cells. Restimulation of
      nonlymphoid memory CD8+ T cells within the skin or mucosa resulted in a
      substantial increase in bona fide Trm cells specifically within draining lymph
      nodes. SLO Trm cells derived from emigrants from nonlymphoid tissues and shared
      some transcriptional and phenotypic signatures associated with nonlymphoid Trm
      cells. These data indicate that nonlymphoid cells can give rise to SLO Trm cells
      and suggest vaccination strategies by which memory CD8+ T cell immunosurveillance
      can be regionalized to specific lymph nodes.

PMID- 29466760
TI  - Recent Advances in Type-2-Cell-Mediated Immunity: Insights from Helminth
      Infection.

PMID- 29466759
TI  - Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized
      in Expansion, Trafficking, and Effector Functions.
AB  - Neutrophils are specialized innate cells that require constant replenishment from
      proliferative bone marrow (BM) precursors as a result of their short half-life.
      Although it is established that neutrophils are derived from the granulocyte
      macrophage progenitor (GMP), the differentiation pathways from GMP to functional
      mature neutrophils are poorly defined. Using mass cytometry (CyTOF) and cell
      cycle-based analysis, we identified three neutrophil subsets within the BM: a
      committed proliferative neutrophil precursor (preNeu) which differentiates into
      non-proliferating immature neutrophils and mature neutrophils. Transcriptomic
      profiling and functional analysis revealed that preNeu require the C/EBPepsilon
      transcription factor for their generation from the GMP, and their proliferative
      program is substituted by a gain of migratory and effector function as they
      mature. preNeus expand under microbial and tumoral stress, and immature
      neutrophils are recruited to the periphery of tumor-bearing mice. In summary, our
      study identifies specialized BM granulocytic populations that ensure supply under
      homeostasis and stress responses.

PMID- 29466761
TI  - NKp46 Receptor-Mediated Interferon-gamma Production by Natural Killer Cells
      Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis.

PMID- 29466762
TI  - Preparation and functional analysis of gossypols having two carbohydrate
      appendages with enaminooxy linkages.
AB  - We developed new gossypol (Gos)-based glycoconjugates through dehydration
      condensation of native Gos and chemically modified glycosides having aminooxy
      groups. The resultant glycoconjugates (glycoGos) were resistant to hydrolysis,
      although they were light-sensitive and slowly decomposed even under indoor
      lighting. The glycoGos also exhibited improved water solubility compared with
      native Gos, but their saturated concentrations in water were still low (6.4-17
      MUM), due to their hydrophobic naphthyl rings. We also carried out WST-8 assays
      to assess the anticancer activity of the glycoGos on DLD-1 and HepG2 cells and
      found that the glycoGos having beta-lactosides and having beta-galactosides
      (specific ligands for asialoglycoprotein receptors) showed enhanced anticancer
      activity on HepG2 cells.

PMID- 29466763
TI  - Discovery and characterization of conserved and novel microRNAs from blunt snout
      bream (Megalobrama amblycephala) by deep sequencing.
AB  - MicroRNAs (miRNAs) are short, single stranded RNA molecules with approximately 22
      nts in length, which regulate the stability and translation of messenger RNAs in
      several organisms. To increase the repertoire of miRNAs characterized in M.
      amblycephala, we used the deep sequencing technology to sequence a small RNA
      library using pooled RNA sample isolated from the 4 different tissues of M.
      amblycephala. A total of 309 conserved miRNAs that originated from 131 miRNA
      families were detected. 15 novel candidates miRNA were identified. Randomly
      selected 6 miRNAs were analyzed by stem-loop qRT-PCR and differential expression
      patterns were observed in 6 different tissues of M. amblycephala. Furthermore,
      the potential targets were predicted. GO analysis showed that most of the targets
      were involved in a broad range of physiological functions including fish growth,
      development, metabolism, stress responses and so on. Overall, our results
      significantly increased the number of novel miRNAs in M. amblycephala, which
      should be useful for further investigation into the role of miRNAs in regulating
      diverse biological processes.

PMID- 29466764
TI  - Molecular characterization of a CONSTANS gene from Sapium sebiferum (L.) Rxob.
AB  - Sapium sebiferum (L.) Roxb [S. sebiferum L.] is not only one of the most
      important economic woody oil trees, but is also a significant traditional herbal
      medicine in China. The CONSTANS (CO) gene is a key regulator of the long day
      dependent flowering pathway in Arabidopsis and other plants. To gain insight into
      the role of CO in woody oil trees, SsCO from S. sebiferum L. was isolated and
      characterized in this study. The corresponding SsCO protein, with 340 amino acid
      residues, included two putative zinc finger motifs B-Box1 and B-Box2 in the N
      terminal region and a conserved CCT domain in the C-terminal region. SsCO
      expression was high in flowers and exhibited distinct circadian regulation. In
      addition, SsCO had a transcriptional activation effect in yeast strains.
      Moreover, heterologous expression of SsCO complemented the late-flowering
      phenotype of the Arabidopsis CO mutant co-1. These results indicate that SsCO is
      a transcription factor and may regulate the photoperiodic flowering time and SsCO
      is regulated by circadian rhythms in Sapium sebiferum L.

PMID- 29466765
TI  - Genetic or pharmacological superoxide-hydrogen peroxide imbalances modulate the
      in vitro effects of lithium on glycogen synthase kinase-3beta.
AB  - INTRODUCTION: Lithium (Li), a mood stabilizer used to treat bipolar disorder (BP)
      symptoms has important anti-inflammatory effects by downregulation of glycogen
      synthase kinase-3 beta (GSK-3beta). However, sometime Li effect is not efficient
      in some patients suggesting genetic interference. Previous investigations
      described association between a genetic superoxide-hydrogen (S-HP) imbalance
      caused by a superoxide dismutase manganese dependent gene polymorphism (Val16Ala
      SOD2 SNP, rs4880) and differential anti-inflammatory response of some drugs and
      bioactive molecules. Therefore, we postulated here that S-HP imbalance could
      present some effect on GSK-3beta modulation by Li. METHODS: to test this
      hypothesis, a genetic and a pharmacological S-HP imbalance protocols were
      performed. In the two protocols, immune cells were activated by phythohemaglutin
      (PHA). The first one, used peripheral blood mononuclear cells (PBMCs) cultures
      carrying different Val16Ala-SOD2 genotypes, and the second used a commercial
      macrophage cell line RAW 264.7. Macrophages were exposed to paraquat to induce
      high S levels (VV-like cells) or porphyrin, that is a SOD2-like molecule that
      increase dismutation of S into HP (AA-like cells). In both protocols the Li
      effects on GSK-3beta gene and protein modulation as evaluated in 24 h cultures.
      The inflammatory activation was also analyzed by cellular proliferation in 72 h
      cell cultures. RESULTS: as expected PHA exposure triggered a strong upregulation
      of GSK-3beta gene expression (p <= 0.001), and Li exposure showed GSK-3beta gene
      downregulation from 0.7 mEq/L concentrations. However, Li modulatory effects on
      GSk-3beta gene and protein expression was directly influenced by basal S-HP
      balance. Presence of high S-basal levels (VV genotype and VV-like cells) induced
      attenuated Li anti-inflammatory effects in comparison with balanced and AA and AA
      like cells (p < 0.001). Despite methodological limitations related to in vitro
      assays, the whole of results suggested that Li anti-inflammatory effects is
      influenced by S-HP basal state and is plausible that its influence could
      contributes to resistance of some patients to Li treatment or to increase of
      intensity of some side effects Li-associated.

PMID- 29466766
TI  - Recent advances in the genomics and therapy of BCR/ABL1-positive and -negative
      chronic myeloproliferative neoplasms.
AB  - This review is based on the presentations and deliberations at the 7th John
      Goldman Chronic Myeloid Leukemia (CML) and Myeloproliferative Neoplasms (MPN)
      Colloquium which took place in Estoril, Portugal on the 15th October 2017, and
      the 11th post-ASH International Workshop on CML and MPN which took place on the
      6th-7th December 2016, immediately after the 58th American Society of Hematology
      Annual Meeting. Rather than present a resume of the proceedings, we have elected
      to address some of the topical translational research and clinically relevant
      topics in greater detail. We address recent updates in the genetics and
      epigenetics of MPN, the mechanisms of transformation by mutant calreticulin,
      advances in the biology and therapy of systemic mastocytosis, clinical updates on
      JAK2 inhibitors and other therapeutic approaches for patients with MPNs,
      cardiovascular toxicity related to tyrosine kinase inhibitors and the concept of
      treatment-free remission for patients with CML.

PMID- 29466767
TI  - 18F-labeled estradiol derivative for targeting estrogen receptor-expressing
      breast cancer.
AB  - INTRODUCTION: A novel radiotracer 1-(2-(2-(2-[18F]fluoroethoxy)ethoxy)ethyl)-1H
      1,2,3-triazole-estradiol ([18F]FETE) was successfully synthesized, characterized
      and evaluated in mice for estrogen receptor (ER)-positive breast cancer targeting
      with positron emission tomography (PET) imaging. METHODS: The tosylate precursor
      3 was radiolabeled with 18F and then reacted with 17alpha-ethinyl-estradiol to
      produce the final [18F]FETE. The physicochemical properties of [18F]FETE were
      tested in vitro, including determination of the octanol/water partition
      coefficient, stability and cellular uptake in MCF-7 (ER-positive) and MDA-MB-231
      (ER-negative) cells. An ex vivo biodistribution study was performed in normal
      Sprague Dawley rats, and in vivo microPET imaging was performed on MCF-7 and MDA
      MB-231 tumor-bearing mice. The results of biodistribution and PET imaging of
      [18F]FETE were compared with that of known 16alpha-[18F]fuoro-17beta-estradiol
      ([18F]FES). Radiation dose estimates for [18F]FETE were also analyzed. RESULTS:
      [18F]FETE was obtained in high radiochemical yield (46.59 +/- 8.06%) with high
      radiochemical purity (>99%) after HPLC purification and high molar activity
      (15.45 +/- 3.15 GBq/MUmol). [18F]FETE is a moderate lipophilic compound with good
      in vitro stability and the total synthesis time was 55 to 65 min. In
      biodistribution studies, [18F]FETE showed high uptake in the ER-abundant uterine
      tissue of normal immature SD rats (8.55 +/- 1.21 and 6.83 +/- 1.70%ID/g at 1 h
      after intravenous and intraperitoneal injection, respectively), and could be
      blocked with estradiol effectively (the uterus uptake was decreased to 0.63 +/-
      0.35%ID/g at 1 h after iv injection). MicroPET imaging of tumor-bearing mice with
      [18F]FETE at 1 h after iv injection revealed considerable uptake in ER-positive
      MCF-7 tumors (4.63 +/- 0.73%ID/g) that could be inhibited (1.47 +/- 0.29%ID/g)
      and low uptake in ER-negative MDA-MB-231 tumors (1.97 +/- 0.36%ID/g). [18F]FES
      has relatively low uptake in ER-positive tumor (0.24 +/- 0.19%ID/g) when compared
      with [18F]FETE. The adult female effective radiation dose of [18F]FETE in mice
      was estimated as 0.0022 mSv/MBq. CONCLUSIONS: A novel 17alpha-ethinyl-estradiol
      based ER probe [18F]FETE was developed with high molar activity and good in vitro
      stability. Based on the results of bio-evaluation in normal immature rats and
      tumor-bearing mice, it might be a promising candidate for specific PET imaging of
      ER-positive breast cancer.

PMID- 29466769
TI  - Insight into the local source of polybrominated diphenyl ethers in the developing
      Tibetan Plateau: The composition and transport around the Lhasa landfill.
AB  - In the background region of the Tibetan Plateau (TP), the rapid urbanization
      probably results in the massive generation of persistent organic pollutants
      (POPs), which lacks monitoring and evaluation. Since landfill could serve as an
      important sink of the locally used POPs, the analysis of POPs in the Tibetan
      landfill area might help us to understand the source composition and their
      transport in the TP. In this study, the concentration variations of
      polybrominated diphenyl ethers (PBDEs) in five soil profiles and seven surficial
      sediments around the largest Tibetan landfill were investigated. The total
      concentrations of PBDEs ranged from 128 to 1219 ng/kg in soils, and from 447 to
      7295 ng/kg in sediments. The dominance of nona- and deca-BDEs possibly indicated
      the wide usage of deca-BDE as flame retardant in the TP. The vertical and spatial
      distribution patterns of PBDEs within soils plausibly revealed their main
      transport pathways by atmospheric dispersion and leachate seepage from landfill.
      Based on principal components analysis and multiple linear regression, these two
      pathways were estimated to account for 61% and 39% of the total concentrations,
      respectively. Additionally, the spatial and vertical distributions of octa-to
      deca-BDEs within soils were significantly influenced by soil particle size.
      Although the PBDEs inventory in the study area was comparatively low, the rapid
      urbanization in the TP might dramatically accelerate the PBDE emissions in the
      future. This study firstly introduced the presence of local PBDEs in the TP, and
      the inventory already influenced the surrounding environment. Once involved in
      the regional cycle of the TP, the local source of PBDEs from waste might
      significantly serve to raise background level resulting otherwise primarily from
      long-range atmospheric transport.

PMID- 29466768
TI  - Dynamics of the Intratumoral Immune Response during Progression of High-Grade
      Serous Ovarian Cancer.
AB  - PURPOSE: Tumor-infiltrating lymphocytes (TILs) have an established impact on the
      prognosis of high-grade serous ovarian carcinoma (HGSOC), however, their role in
      recurrent ovarian cancer is largely unknown. We therefore systematically
      investigated TIL densities and MHC class I and II (MHC1, 2) expression in the
      progression of HGSOC. EXPERIMENTAL DESIGN: CD3+, CD4+, CD8+ TILs and MHC1, 2
      expression were evaluated by immunohistochemistry on tissue microarrays in 113
      paired primary and recurrent HGSOC. TILs were quantified by image analysis. All
      patients had been included to the EU-funded OCTIPS FP7 project. RESULTS: CD3+,
      CD4+, CD8+ TILs and MHC1 and MHC2 expression showed significant correlations
      between primary and recurrent tumor levels (Spearman rho 0.427, 0.533, 0.361,
      0.456, 0.526 respectively; P<.0001 each). Paired testing revealed higher CD4+
      densities and MHC1 expression in recurrent tumors (Wilcoxon P=.034 and P=.018).
      There was also a shift towards higher CD3+ TILs levels in recurrent carcinomas
      when analyzing platinum-sensitive tumors only (Wilcoxon P=.026) and in pairs with
      recurrent tumor tissue from first relapse only (Wilcoxon P=.031). High MHC2
      expression was the only parameter to be significantly linked to prolonged
      progression-free survival after first relapse (PFS2, log-rank P=.012).
      CONCLUSIONS: This is the first study that analyzed the development of TILs
      density and MHC expression in paired primary and recurrent HGSOC. The level of
      the antitumoral immune response in recurrent tumors was clearly dependent on the
      one in the primary tumor. Our data contribute to the understanding of temporal
      heterogeneity of HGSOC immune microenvironment and have implications for
      selection of samples for biomarker testing in the setting of immune-targeting
      therapeutics.

PMID- 29466770
TI  - Neonatal triphenyl phosphate and its metabolite diphenyl phosphate exposure
      induce sex- and dose-dependent metabolic disruptions in adult mice.
AB  - The widespread application of organophosphorous flame retardants (OPFRs) has led
      to considerable human exposure, with major concerns regarding their health risks.
      Herein, we investigate the effects of triphenyl phosphate (TPP), one of the most
      widely used OPFRs, and one of its main metabolite diphenyl phosphate (DPP) on the
      endocrine systems and metabolic profiles after neonatal exposure from postnatal
      days 1-10 at two dosages (2 and 200 MUg per day). Both TPP and DPP had no
      negative effect on uterine weight, glucose tolerance, and estradiol. 1H-NMR-based
      metabolomics revealed a sex-specific metabolic disturbance of TPP. Specifically,
      low dose of TPP altered the metabolic profiles of male mice while exerting no
      significant effects on female ones. Furthermore, a dose-dependent effect of TPP
      in male mice was observed, where a low toxicity dose up-regulated lipid-related
      metabolites, while a high toxicity dose down-regulated the pyruvate metabolism
      and TCA cycles. These results highlight the importance of carefully assessing the
      health impact of TPP on infants.

PMID- 29466771
TI  - Effects of prenatal exposure to air pollution on preeclampsia in Shenzhen, China.
AB  - The impact of ambient air pollution on pregnant women is a concern in China.
      However, little is known about the association between air pollution and
      preeclampsia and the potential modifying effects of meteorological conditions
      have not been assessed. This study aimed to assess the effects of prenatal
      exposure to air pollution on preeclampsia, and to explore whether temperature and
      humidity modify the effects. We performed a retrospective cohort study based on
      1.21 million singleton births from the birth registration system in Shenzhen,
      China, between 2005 and 2012. Daily average measurements of particulate matter
      <10 MUm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), air temperature
      (T), and dew point (Td) were collected. Logistic regression models were performed
      to estimate associations between air pollution and preeclampsia during the first
      and second trimesters, and during the entire pregnancy. In each time window, we
      observed a positive gradient of increasing preeclampsia risk with increasing
      quartiles of PM10 and SO2 exposure. When stratified by T and Td in three
      categories (<5th, 5th -95th, and >95th percentile), we found a significant
      interaction between PM10 and Td on preeclampsia; the adverse effects of PM10
      increased with Td. During the entire pregnancy, there was a null association
      between PM10 and preeclampsia under Td < 5th percentile. Preeclampsia risk
      increased by 23% (95% CI: 19-26%) when 5th < Td < 95th percentile, and by 34% (16
      55%) when Td > 95th percentile. We also found that air pollution effects on
      preeclampsia in autumn/winter seasons were stronger than those in the
      spring/summer. This is the first study to address modifying effects of
      meteorological factors on the association between air pollution and preeclampsia.
      Findings indicate that prenatal exposure to PM10 and SO2 increase preeclampsia
      risk in Shenzhen, China, and the effects could be modified by humidity. Pregnant
      women should limit air pollution exposure, particularly during humid periods.

PMID- 29466772
TI  - Effects of Fe-S-As coupled redox processes on arsenic mobilization in shallow
      aquifers of Datong Basin, northern China.
AB  - High arsenic groundwater generally coexists with elevated Fe2+ concentrations (mg
      L-1 levels) under reducing conditions, but an explanation for the extremely high
      arsenic (up to ~2690) concentrations at very low Fe2+ (i.e., MUg L-1 levels) in
      groundwater of Datong Basin remains elusive. Field groundwater investigation and
      laboratory microcosm experiments were implemented in this study. The field
      groundwater was characterized by weakly alkaline (pH 7.69 to 8.34) and reducing
      conditions (Eh -221.7 to -31.9 mV) and arsenic concentration averages at 697 MUg
      L-1. Acinetobacter (5.9-51.3%), Desulfosporosinus (4.6-30.2%), Brevundimonas (3.9
      19%) and Pseudomonas (3.2-14.6%) were identified as the dominant genera in the
      bacterial communities. Bacterially mediated arsenate reduction, Fe(III)
      reduction, and sulfate reduction are processes occurring (or having previously
      occurred) in the groundwater. Results from incubation experiment (27 d) revealed
      that nitrate, arsenate, and Fe(III)/sulfate reduced sequentially with time under
      anoxic conditions, while Fe(III) and sulfate reduction processes had no obvious
      differences, occurring almost simultaneously. Moreover, low Fe2+ concentrations
      were attributed to initially high pH conditions, which relatively retarded
      Fe(III) reduction. In addition, arsenic behavior in relation to groundwater redox
      conditions, matrices, and solution chemistry were elaborated. Bacterial arsenate
      reduction process proceeded before Fe(III) and sulfate reduction in the
      incubation experiment, and the total arsenic concentration (dominated by
      arsenite) gradually increased from ~7 to 115 MUg L-1 as arsenate was reduced.
      Accordingly, bacterially mediated reductive desorption of arsenate is identified
      as the main process controlling arsenic mobility, while Fe(III) reduction coupled
      with sulfate reduction are secondary processes that have also contributed to
      arsenic enrichment in the study site. Overall, this study provide important
      insights into the mechanism controlling arsenic mobility under weakly alkaline
      and reducing conditions, and furnishes that arsenate reduction by bacteria play a
      major role leading to high accumulation of desorbed arsenite in groundwater.

PMID- 29466773
TI  - Discovery of 2,4,6-trisubstitued pyrido[3,4-d]pyrimidine derivatives as new EGFR
      TKIs.
AB  - Targeting acquired drug resistance is the major challenge in the treatment of
      EGFR-driven non-small cell lung cancer (NSCLC). In this study, a novel class of
      compounds containing pyrido[3,4-d]pyrimidine scaffold was designed as new
      generation EGFR-TKIs to overcome this challenge. The most promising compound B30
      inhibited HCC827 and H1975 cells growth with the IC50 values of 0.044 MUM and
      0.40 MUM, respectively. Meanwhile, B30 displayed potent inhibitory activity
      against the EGFRL858R (IC50 = 1.1 nM) and EGFRL858R/T790M/C797S (IC50 = 7.2 nM).
      B30 could suppress EGFR phosphorylation in a dose-dependent manner in HCC827 cell
      line and significantly induce the apoptosis of HCC827 cells. Molecular docking
      indicated that the hydroxyl in B30 could form additional hydrogen bond with
      mutant Ser797. These findings strongly support our assumption that 2,4,6
      trisubstitued pyrido[3,4-d] pyrimidine derivatives can serve as EGFR-TKIs. The
      predicted hydrogen bond interaction formed by a small molecule inhibitor with
      mutant Ser797 is available to design the fourth-generation EGFR-TKIs.

PMID- 29466774
TI  - Synthesis and activity towards Alzheimer's disease in vitro: Tacrine, phenolic
      acid and ligustrazine hybrids.
AB  - A series of novel tacrine-phenolic acid dihybrids and tacrine-phenolic acid
      ligustrazine trihybrids were synthesized, characterized and screened as novel
      potential anti-Alzheimer drug candidates. These compounds showed potent
      inhibition activity towards cholinesterases (ChEs), among of them, 9i was the
      most potent one towards acetylcholinesterase (eeAChE, IC50 = 3.9 nM; hAChE, IC50
      = 65.2 nM). 9i could also effectively block beta-amyloid (Abeta) self-aggregation
      with an inhibition ratio of 47% at 20 MUM. In addition, its strong anti-oxidation
      activity could protect PC12 cells from CoCl2-damage in the experimental condition
      while no neurotoxicity. Furthermore, its hepatotoxicity was lower than tacrine in
      vitro and in vivo. Kinetic and molecular modeling studies revealed that 9i worked
      in a mixed-type way, could interact simultaneously with catalytic active site
      (CAS) and peripheral anionic site (PAS) of AChE. Therefore, 9i was a promising
      multifunctional candidate for the treatment of AD.

PMID- 29466775
TI  - Novel Tacrine-Hydroxyphenylbenzimidazole hybrids as potential multitarget drug
      candidates for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a severe age-dependent neurodegenerative disorder
      affecting millions of people, with no cure so far. The current treatments only
      achieve some temporary amelioration of the cognition symptoms. The main
      characteristics of the patient brains include the accumulation of amyloid plaques
      and neurofibrillary tangles (outside and inside the neurons) but also cholinergic
      deficit, increased oxidative stress and dyshomeostasis of transition metal ions.
      Considering the multi-factorial nature of AD, we report herein the development of
      a novel series of potential multi-target directed drugs which, besides the
      capacity to recover the cholinergic neurons, can also target other AD hallmarks.
      The novel series of tacrine-hydroxyphenylbenzimidazole (TAC-BIM) hybrid molecules
      has been designed, synthesized and studied for their multiple biological
      activities. These agents showed improved AChE inhibitory activity (IC50 in
      nanomolar range), as compared with the single drug tacrine (TAC), and also a high
      inhibition of self-induced- and Cu-induced-Abeta aggregation (up to 75%). They
      also present moderate radical scavenging activity and metal chelating ability. In
      addition, neuroprotective studies revealed that all these tested compounds are
      able to inhibit the neurotoxicity induced by Abeta and Fe/AscH(-) in neuronal
      cells. Hence, for this set of hybrids, structure-activity relationships are
      discussed and finally it is highlighted their real promising interest as
      potential anti-AD drugs.

PMID- 29466776
TI  - Structure-based discovery of cytotoxic dimeric tetrahydroxanthones as potential
      topoisomerase I inhibitors from a marine-derived fungus.
AB  - DNA topoisomerase I (Topo I) is an important anticancer drug target, and xanthone
      dimers are considered to be a new kind of Topo I inhibitor chemotypes. Based on
      the characteristics of dimeric xanthone structures, five new dimeric xanthones (1
      5) and two known SAD isomers (6 and 7) were isolated from the mangrove-derived
      fungus Aspergillus vericolor. The absolute configurations of compounds 1-7,
      entailing both central and axial chirality elements, were established by a
      combination of ECD comparison, chemical conversions, and biogenetic
      considerations. Compounds 1-7 possessed high structural diversity and exhibited
      cytotoxicity at different levels. The selected new compounds 1, 2, and 5 showed
      Topo I inhibition properties and the most potent compound 1, an atropisomer of
      compound 2, was confirmed to inhibit Topo I-mediated DNA relaxation by targeting
      Topo I, thereby, arresting the cell cycle process and inducing necrosis in cancer
      cells. Molecular docking studies showed that compound 1 could bind DNA by pi-pi
      interaction and DNA Topo I by hydrogen bonds to form a ternary complex.

PMID- 29466777
TI  - Synthesis and biological evaluation of 20-epi-amino-20-deoxysalinomycin
      derivatives.
AB  - To improve the druggability of salinomycin, a 20-epi-amino-20-deoxysalinomycin
      derivatives library was synthesized with high efficacy from which a few
      salinomycin derivatives with high potency and selectivity were identified through
      comprehensive cytotoxicity assay, including a fluorine-19 magnetic resonance
      sensitive tool molecule. Using a K-ras cellular model, salinomycin and its
      derivatives showed different molecular mode of action from literature reports.
      These results would be valuable for developing salinomycin-based cancer therapy.

PMID- 29466778
TI  - New MD2 inhibitors derived from curcumin with improved anti-inflammatory
      activity.
AB  - An overactive Toll-like receptor (TLR) signaling complex is a significant
      pathogenic factor of acute and chronic inflammatory diseases. The natural product
      curcumin is reported to inhibit the TLR4 co-receptor, MD2 (myeloid
      differentiation protein 2), but its low in vivo bioavailability limits its
      therapeutic potential. We developed new curcumin analogs (MACs) with removal of
      the beta-diketone moiety and substituted residues in benzene rings, and identify
      these as potential MD2 inhibitors with improved inhibition potency and stability
      over that of curcumin. Specifically, MAC 17 and 28 showed the highest anti
      inflammatory activity, with >90% inhibition of LPS-stimulated cytokine secretion
      from macrophages, and protected against LPS-induced acute lung injury and sepsis.
      The MACs inhibited the TLR4-MD2 signaling complex through competition with LPS
      for binding on MD2, likely at Arg90. Our findings indicated that MAC 17 and 28
      are promising candidates for future development as therapeutic drugs for
      inflammatory diseases with an endotoxin etiology.

PMID- 29466779
TI  - Simultaneous decomplexation in blended Cu(II)/Ni(II)-EDTA systems by electro
      Fenton process using iron sacrificing electrodes.
AB  - This research explored the application of electro-Fenton (E-Fenton) technique for
      the simultaneous decomplexation in blended Cu(II)/Ni(II)-EDTA systems by using
      iron sacrificing electrodes. Standard discharge (0.3 mg L-1 for Cu and 0.1 mg L-1
      for Ni in China) could be achieved after 30 min reaction under the optimum
      conditions (i.e. initial solution pH of 2.0, H2O2 dosage of 6 mL L-1 h-1, current
      density of 20 mA/cm2, inter-electrode distance of 2 cm, and sulfate electrolyte
      concentration of 2000 mg L-1). The distinct differences in apparent kinetic rate
      constants (kapp) and intermediate removal efficiencies corresponding to mere and
      blended systems indicated the mutual promotion effect toward the decomplexation
      between Cu(II) and Ni(II). Massive accumulation of Fe(III) favored the further
      removal of Cu(II) and Ni(II) by metal ion substitution. Species distribution
      results demonstrated that the decomplexation of metal-EDTA in E-Fenton process
      was mainly contributed to the combination of various reactions, including Fenton
      reaction together with the anodic oxidation, electro-coagulation (E-coagulation)
      and electrodeposition. Unlike hypophosphite and citrate, the presence of chlorine
      ion displayed favorable effects on the removal efficiencies of Cu(II) and Ni(II)
      at low dosage, but facilitated the ammonia nitrogen (NH4+-N) removal only at high
      dosage.

PMID- 29466780
TI  - A novel polymer probe for Zn(II) detection with ratiometric fluorescence signal.
AB  - A conjugated polymer probe comprised of fluorene, quinolone and benzothiazole
      units was designed and synthesized by the Suzuki coupling reaction. Through the
      studies of photophysical and thermal properties, the polymer displays blue
      emitting feature and good thermal stability. A ratiometric fluorescence signal of
      the probe for Zn(II) was observed in ethanol with a new emission peak at 555 nm.
      The probe possesses a high selectivity and sensitivity for Zn(II) during familiar
      metal ions in ethanol. The detection limit of the probe for Zn (II) is up to 10-8
      mol/L. The electron distributions of the polymer before and after bonding with Zn
      (II) were investigated by the Gaussian 09 software, which agreed with the
      experimental results. Noticeably, based on the color property of the probe with
      Zn(II), a series of color test paper were developed for visual detecting Zn(II)
      ions. This work helps to provide a platform or pattern for the development of
      polymer fluorescence probe in the chemosensor field.

PMID- 29466781
TI  - An active learning representative subset selection method using net analyte
      signal.
AB  - To guarantee accurate predictions, representative samples are needed when
      building a calibration model for spectroscopic measurements. However, in general,
      it is not known whether a sample is representative prior to measuring its
      concentration, which is both time-consuming and expensive. In this paper, a
      method to determine whether a sample should be selected into a calibration set is
      presented. The selection is based on the difference of Euclidean norm of net
      analyte signal (NAS) vector between the candidate and existing samples. First,
      the concentrations and spectra of a group of samples are used to compute the
      projection matrix, NAS vector, and scalar values. Next, the NAS vectors of
      candidate samples are computed by multiplying projection matrix with spectra of
      samples. Scalar value of NAS is obtained by norm computation. The distance
      between the candidate set and the selected set is computed, and samples with the
      largest distance are added to selected set sequentially. Last, the concentration
      of the analyte is measured such that the sample can be used as a calibration
      sample. Using a validation test, it is shown that the presented method is more
      efficient than random selection. As a result, the amount of time and money spent
      on reference measurements is greatly reduced.

PMID- 29466782
TI  - Estimation of light source colours for light pollution assessment.
AB  - The concept of the smart city raised several technological and scientific issues
      including light pollution. There are various negative impacts of light pollution
      on economy, ecology, and heath. This paper deals with the census of the colour of
      light emitted by lamps used in a city environment. To this end, we derive a light
      bulb colour estimator based on Bayesian reasoning, directional data, and image
      formation model in which the usual concept of reflectance is not used. All
      choices we made are devoted to designing an algorithm which can be run almost in
      real-time. Experimental results show the effectiveness of the proposed approach.

PMID- 29466783
TI  - Knockout of Low Molecular Weight FGF2 Attenuates Atherosclerosis by Reducing
      Macrophage Infiltration and Oxidative Stress in Mice.
AB  - BACKGROUND/AIMS: Fibroblast growth factor 2 (FGF2) plays a predominant role
      during angiogenesis in the adventitia and in atherosclerotic plaque. A dilemma
      exists, however, as to whether angiogenic stimulation by FGF2 for the prevention
      and treatment of atherogenesis is feasible. The aim of this study is to
      investigate the effect of the 18-kDa FGF-2 isoform on atherosclerosis progression
      in high-fat diet-fed apolipoprotein E knockout (ApoE-/-) mice. METHODS: We
      established a model of atherosclerosis using ApoE and 18-kDa FGF-2 gene double
      knockout mice. They were randomly divided into three groups depending on the
      duration of diet: 8 weeks, 12 weeks and 16 weeks. Then, we studied the morphology
      and inflammatory factor staining in the atherosclerosis plaque of these mice.
      RESULTS: Knockout of the 18-kDa FGF-2 isoform did not change the metabolic
      characteristics of the mice. Compared to the control group, knockout of the 18
      kDa FGF-2 isoform significantly attenuated atherogenesis, reduced aortic plaques,
      reduced macrophage infiltration and suppressed oxidative stress in mice fed with
      a high fat diet at all-time points. CONCLUSIONS: 18-kDa FGF-2 aggravated the
      inflammatory reaction of atherosclerosis.

PMID- 29466784
TI  - Clinical, Hormonal, and Genetic Evaluation of Idiopathic Nonobstructive
      Azoospermia and Klinefelter Syndrome Patients.
AB  - To investigate the clinical, hormonal, and genetic factors in infertile men with
      idiopathic nonobstructive azoospermia (NOA) or azoospermic Klinefelter syndrome
      (KFS), a total of 556 and 96 patients, respectively, were included in this study.
      All patient samples were analyzed cytogenetically. Serum reproductive hormone
      levels were measured. Microdeletions in the azoospermia factor (AZF) region of
      the Y chromosome were detected by multiplex PCR using 16 specific sequence-tagged
      sites. FSH and LH levels in both NOA and KFS patients were significantly higher
      than the normal range, and the testosterone level in KFS patients was
      significantly lower. Ninety-two (95.8%) of the KFS patients showed non-mosaic
      47,XXY karyotypes and 47,XXY,inv(9)(p11.1q13); the other KFS patients had mosaic
      karyotypes of 47,XXY/46,XY, 47,XXY/46,XX, and 47,XXY/48,XXXY/46,XX. Among the 556
      idiopathic NOA patients with normal karyotypes, 67 (12.05%) had microdeletions in
      the AZF region of the Y chromosome. Microdeletions were most frequently detected
      in the AZFc region, followed by AZFa, AZFb, AZFbc, and partial AZFc deletions.
      However, Y chromosome microdeletions were not found in any of the azoospermic KFS
      patients. In view of the hormonal and genetic abnormalities in infertile men with
      idiopathic NOA and with azoospermic KFS, genetic testing for karyotype, Y
      chromosome microdeletions, and hormonal parameters is advocated.

PMID- 29466785
TI  - Down-Regulation of H3K4me3 by MM-102 Facilitates Epigenetic Reprogramming of
      Porcine Somatic Cell Nuclear Transfer Embryos.
AB  - BACKGROUND/AIMS: Aberrantly high levels of H3K4me3, caused by incomplete
      epigenetic reprogramming, likely cause a low efficiency of somatic cell nuclear
      transfer (SCNT). Smal molecule inhibitors aimed at epigenetic modification can be
      used to improve porcine SCNT embryo development. In this study, we examined the
      effects of MM-102, an H3K4 histone methyltransferase inhibitor, on porcine SCNT
      preimplantation embryos to investigate the mechanism by which H3K4 methylation
      regulated global epigenetic reprograming during SCNT. METHODS: MM-102 was added
      to the SCNT embryos culture system and the global levels of various epigenetic
      modifications were measured by immunofluorescence (IF) staining and were
      quantified by Image J software. Relative genes expression levels were detected by
      quantitative real-time PCR. RESULTS: MM-102 (75 MUM) treatment reduced global
      H3K4, H3K9 methylation and 5mC levels especially at the zygotic gene activation
      (ZGA) and blastocyst stages. MM-102 treatment mainly down-regulated a series of
      DNA and histone methyltransferases, and up-regulated a number of hitone
      acetyltransferases and transcriptional activators. Furthermore, MM-102 treatment
      positively regulated the mRNA expression of genes related to pluripotency (OCT4,
      NANOG, CDX2) and apoptosis (BCL2). CONCLUSION: Down-regulation of H3K4me3 with MM
      102 rescued aberrant gene expression patterns of a series of epigenetic chromatin
      modification enzymes, pluripotent and apoptotic genes at the ZGA and blastocyst
      stages, thereby greatly improving porcine SCNT efficiency and blastocyst quality,
      making them more similar to in vivo embryos (IVV).

PMID- 29466786
TI  - Long-Term Vitamin D Supplementation and the Effects on Recurrence and Metabolic
      Status of Cervical Intraepithelial Neoplasia Grade 2 or 3: A Randomized, Double
      Blind, Placebo-Controlled Trial.
AB  - OBJECTIVE: This study was conducted to evaluate the effects of vitamin D
      supplementation on the recurrence and metabolic status of patients with cervical
      intraepithelial neoplasia grade 2 or 3 (CIN2/3). METHODS: This randomized, double
      blind, placebo-controlled trial was carried out among 58 women diagnosed with
      CIN2/3. Participants were randomly assigned into 2 groups to receive either
      50,000 IU vitamin D3 (n = 29) or placebo (n = 29) every 2 weeks for 6 months.
      RESULTS: The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and
      placebo groups respectively (p = 0.02). When we excluded CIN1, the recurrence
      rate of CIN2/3 became nonsignificant. Vitamin D supplementation significantly
      decreased fasting plasma glucose (-7.8 +/- 9.2 vs. -1.1 +/- 8.6 mg/dL, p = 0.006)
      and insulin levels (-3.2 +/- 4.8 vs. -0.9 +/- 3.4 uIU/mL, p = 0.03), and
      significantly increased quantitative insulin sensitivity check index (0.01 +/-
      0.02 vs. 0.002 +/- 0.01, p = 0.02) compared with the placebo. Additionally, there
      was a significant decrease in high-sensitivity C-reactive protein (-815.3 +/-
      1,786.2 vs. 717.5 +/- 1,827.3 ng/mL, p = 0.002) and a significant increase in
      total antioxidant capacity (113.4 +/- 137.4 vs. -53.7 +/- 186.7 mmol/L, p <
      0.001) following the supplementation of vitamin D compared with the placebo.
      CONCLUSIONS: Vitamin D3 supplementation for 6 months among women with CIN2/3 had
      beneficial effects on CIN1/2/3 recurrence and metabolic status; however, it did
      not affect CIN2/3 recurrence.

PMID- 29466787
TI  - A Strategy for Optimizing the Combination of Active Components Based on Chinese
      Medicinal Formula Sheng-Mai-San for Myocardial Ischemia.
AB  - BACKGROUND/AIMS: Traditional Chinese medicine (TCM) has been used in clinical
      practice for thousands of years and has accumulated considerable knowledge
      concerning the in vivo efficacy of targeting complicated diseases. TCM formulae
      are a mixture of hundreds of chemical components with multiple potential targets,
      essentially acting as a combination therapy of multi-component drugs. However,
      the obscure substances and the unclear molecular mechanisms are obstacles to
      their further development and internationalization. Therefore, it is necessary to
      develop new modern drugs based on the combination of effective components in TCM
      with exact clinical efficacy. In present study, we aimed to detect optimal ratio
      of the combination of effective components based on Sheng-Mai-San for myocardial
      ischemia. METHODS: On the basis of preliminary studies and references of relevant
      literature about Sheng-Mai-San for myocardial ischemia, we chose three
      representative components (ginsenoside Rb1 (G), ruscogenin (R) and schisandrin
      (S)) for the optimization design studies. First, the proper proportion of the
      combination was explored in different myocardial ischemia mice induced by
      isoproterenol and pituitrin based on orthogonal design. Then, the different
      proportion combinations were further optimized through uniform design in a multi
      model and multi-index mode. Finally, the protective effect of combination was
      verified in three models of myocardial ischemia injured by ischemia/reperfusion,
      chronic intermittent hypoxia and acute infarction. RESULTS: The optimized
      combination GRS (G: 6 mg/kg, R: 0.75 mg/kg, S: 6 mg/kg) obtained by experimental
      screening exhibited a significant protective effect on myocardial ischemia
      injury, as evidenced by decreased myocardium infarct size, ameliorated
      histological features, decreased myocardial myeloperoxidase (MPO) and
      malondiadehyde (MDA), calcium overload, and decreased serum lactate dehydrogenase
      (LDH), creatine kinase MB isoenzyme (CK-MB), cardiac troponin I (cTn-I) activity.
      In addition, the interactions of three components in combination GRS were also
      investigated. The combination, compared to G, R and S, could significantly reduce
      the concentration of serum CK-MB and cTn-I, and decrease myocardial infarct size,
      which demonstrated the advantages of this combination for myocardial ischemia.
      CONCLUSION: Our results demonstrated that the optimized combination GRS could
      exert significant cardioprotection against myocardial ischemia injury with
      similar effect compared to Sheng Mai preparations, which might provide some
      pharmacological evidences for further development of new modern Chinese drug for
      cardiovascular diseases basing on traditional Chinese formula with affirmative
      therapeutic effect.

PMID- 29466788
TI  - Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the
      Livers of Non-Alcoholic Fatty Liver Disease Mice.
AB  - BACKGROUND/AIMS: Recent studies have suggested that changes in non-coding mRNA
      play a key role in the progression of non-alcoholic fatty liver disease (NAFLD).
      Metformin is now recommended and effective for the treatment of NAFLD. We hope
      the current analyses of the non-coding mRNA transcriptome will provide a better
      presentation of the potential roles of mRNAs and long non-coding RNAs (lncRNAs)
      that underlie NAFLD and metformin intervention. METHODS: The present study mainly
      analysed changes in the coding transcriptome and non-coding RNAs after the
      application of a five-week metformin intervention. Liver samples from three
      groups of mice were harvested for transcriptome profiling, which covered mRNA,
      lncRNA, microRNA (miRNA) and circular RNA (circRNA), using a microarray
      technique. RESULTS: A systematic alleviation of high-fat diet (HFD)-induced
      transcriptome alterations by metformin was observed. The metformin treatment
      largely reversed the correlations with diabetes-related pathways. Our analysis
      also suggested interaction networks between differentially expressed lncRNAs and
      known hepatic disease genes and interactions between circRNA and their disease
      related miRNA partners. Eight HFD-responsive lncRNAs and three metformin
      responsive lncRNAs were noted due to their widespread associations with disease
      genes. Moreover, seven miRNAs that interacted with multiple differentially
      expressed circRNAs were highlighted because they were likely to be associated
      with metabolic or liver diseases. CONCLUSIONS: The present study identified novel
      changes in the coding transcriptome and non-coding RNAs in the livers of NAFLD
      mice after metformin treatment that might shed light on the underlying mechanism
      by which metformin impedes the progression of NAFLD.

PMID- 29466789
TI  - Two-Port Fetoscopic Repair of Myelomeningocele in Fetal Lambs.
AB  - OBJECTIVE: The aim of this study was to assess the feasibility and the
      effectiveness of a fetoscopic myelomeningocele (MMC) repair with a running single
      suture using a 2-port access in the sheep model. METHODS: Eighteen fetuses
      underwent surgical creation of a MMC defect at day 75. Fetuses were then
      randomized into 3 groups. Four fetuses remained untreated (control group). In the
      other 14 fetuses, a prenatal repair was performed at day 90: 7 fetuses had an
      open repair (oMMC), and 7 fetuses had a fetoscopic repair (fMMC) using a single
      layer running suture through a 2-port access. Lambs were sacrificed at term, and
      histological examinations were performed. RESULTS: Hindbrain herniation was
      observed in all live lambs in the control group. A complete closure of the defect
      was achieved in all the lambs of the fMMC group. A complete healing of the defect
      and no hindbrain herniation were observed in all live lambs of the oMMC and fMMC
      groups. The durations of surgeries were not statistically different between the
      oMMC and the fMMC groups (60 vs. 53 min, p = 0.40), as was the risk of fetal loss
      (fMMC: 1/7, oMMC: 3/7, p = 0.56). DISCUSSION: Fetoscopic repair of MMC can be
      performed using a single-layer running suture through a 2-port access and may be
      promising to reduce the risk of premature rupture of membranes.

PMID- 29466790
TI  - Elevated Faecal Calprotectin Levels are a Reliable Non-Invasive Screening Tool
      for Small Bowel Crohn's Disease in Patients Undergoing Capsule Endoscopy.
AB  - BACKGROUND: Approximately 10% of Crohn's disease (CD) patients have this disease
      affecting the small bowel (SB) beyond the reach of Ileo-colonoscopy. Capsule
      endoscopy (SBCE) is the recommended investigation for SB disease. An accurate and
      inexpensive biomarker would help identify at-risk patients. AIM: To examine the
      efficacy of faecal calprotectin (FC) and C-reactive protein (CRP) as predictors
      of SBCE findings in suspected and known CD. METHODS: A prospective observational
      study. Consecutive patients referred for SBCE gave FC and CRP samples. The
      diagnostic accuracy for SB CD based on SBCE result was calculated for both FC and
      CRP. RESULTS: Of 100 invitees, FC and SBCE results were available in 64 cases.
      Correlation between FC >50 ug/g and SBCE result was poor K = 0.163; sensitivity,
      specificity, positive predictive value (PPV) and negative predictive values for
      ileitis were 60, 61, 32 and 83% respectively. PPV and specificity improved at FC
      >100 ug/g, 76 and 40%, correlation remained fair, K = 0.259. Receiver operating
      characteristic analysis had a sensitivity of 47% and specificity of 90% for FC
      >194 ug/g. CRP alone or in combination was an inaccurate predictor of ileitis.
      CONCLUSION: Our study suggests that FC level >194 ug/g may be a useful SBCE
      filter test, identifying patients at risk of SB CD.

PMID- 29466792
TI  - A New Chance for Hyperimmunized Patients in Renal Transplant Waiting List from
      Tolerance Induction: The Emerging Link between Human Leukocyte Antigen G, T
      Regulatory Cells, and Neutrophil Gelatinase-Associated Lipocalin.

PMID- 29466791
TI  - Lysophosphatidic Acid Induces Ligamentum Flavum Hypertrophy Through the LPAR1/Akt
      Pathway.
AB  - BACKGROUND/AIMS: Hypertrophic ligamentum flavum (LF) is a major cause of lumbar
      spinal stenosis. Our previous work showed that high levels of lysophosphatidic
      acid (LPA) expression are positively correlated with LF hypertrophy. This study
      aimed to further unveil how LPA regulates LF hypertrophy Methods: We studied
      LPAR1 expression in human LF cells using PCR and western blotting. Cell viability
      cell cycle, apoptosis rate and molecular mechanisms were assayed in LPAR1
      knockdown or overexpression LF cells. LF hypertrophy and the molecular mechanism
      was confirmed in human samples and in in vivo studies. RESULTS: The expression of
      LPA and its receptor LPAR1 is significantly higher in tissues or cells harvested
      from hypertrophic LF compared to healthy controls. Moreover, LPA promoted LF cell
      proliferation by interacting with LPAR1. This conclusion is supported by the fact
      that depletion or overexpression of LPAR1 changed the effect of LPA on LF cell
      proliferation. LPA also inhibits apoptosis in LF cells through the receptor
      LPAR1. Importantly, we demonstrated that the LPA-LPAR1 interaction initiated Akt
      phosphorylation and determined cell proliferation and apoptosis. Our in vitro
      findings were supported by our in vivo evidence that lyophilized LPA
      significantly induced LF hypertrophy via the LPAR1-Akt signaling pathway. More
      importantly, targeted inhibition of LPAR1 by Ki16425 with a gel sponge implant
      effectively reduced LPA-associated LF hypertrophy. Taken together, these data
      indicate that LPA binds to the receptor LPAR1 to induce LF cell proliferation and
      inhibit apoptosis by activating AKT signaling cascades. Targeting this signaling
      cascade with Ki16425 is a potential therapeutic strategy for preventing LF
      hypertrophy. CONCLUSION: LPA-LPAR1-Akt activation is positively correlated with
      the proliferation and survival of LF cells. LPAR1 could be a target for new drugs
      and the development of new therapeutic methods for treating LF hypertrophy.

PMID- 29466793
TI  - A Novel Method to Detect Early Colorectal Cancer Based on Chromosome Copy Number
      Variation in Plasma.
AB  - BACKGROUND/AIMS: Colonoscopy screening has been accepted broadly to evaluate the
      risk and incidence of colorectal cancer (CRC) during health examination in
      outpatients. However, the intrusiveness, complexity and discomfort of colonoscopy
      may limit its application and the compliance of patients. Thus, more reliable and
      convenient diagnostic methods are necessary for CRC screening. Genome
      instability, especially copy-number variation (CNV), is a hallmark of cancer and
      has been proved to have potential in clinical application. METHODS: We determined
      the diagnostic potential of chromosomal CNV at the arm level by whole-genome
      sequencing of CRC plasma samples (n = 32) and healthy controls (n = 38). Arm
      level CNV was determined and the consistence of arm-level CNV between plasma and
      tissue was further analyzed. Two methods including regular z score and trained
      Support Vector Machine (SVM) classifier were applied for detection of colorectal
      cancer. RESULTS: In plasma samples of CRC patients, the most frequent deletions
      were detected on chromosomes 6, 8p, 14q and 1p, and the most frequent
      amplifications occurred on chromosome 19, 5, 2, 9p and 20p. These arm-level
      alterations detected in plasma were also observed in tumor tissues. We showed
      that the specificity of regular z score analysis for the detection of colorectal
      cancer was 86.8% (33/38), whereas its sensitivity was only 56.3% (18/32).
      Applying a trained SVM classifier (n = 40 in trained group) as the standard to
      detect colorectal cancer relevance ratio in the test samples (n = 30), a
      sensitivity of 91.7% (11/12) and a specificity 88.9% (16/18) were finally
      reached. Furthermore, all five early CRC patients in stages I and II were
      successfully detected. CONCLUSION: Trained SVM classifier based on arm-level CNVs
      can be used as a promising method to screen early-stage CRC.

PMID- 29466794
TI  - FOXO1, a Potential Therapeutic Target, Regulates Autophagic Flux, Oxidative
      Stress, Mitochondrial Dysfunction, and Apoptosis in Human Cholangiocarcinoma
      QBC939 Cells.
AB  - BACKGROUND/AIMS: Autophagy is an evolutionarily conserved catabolic mechanism to
      maintain energy homeostasis and to remove damaged cellular components, which
      plays an important role in the survival of various cells. Inhibiting autophagy is
      often applied as a new strategy to halt the growth of cancer cells. METHODS: The
      effect of FOXO1 gene on cellular function and apoptosis and its underlying
      mechanisms were investigated in cultured QBC939 cells by the
      methylthiazoletetrazolium (MTT) assay, western blot, DCFDA mitochondrial membrane
      potential, and ATP content measurement. FOXO1 siRNA was applied to down-regulate
      FOXO1 expression in QBC939 cells. RESULTS: Here we reported that FOXO1,
      acetylation of FOXO1 (Ac-FOXO1) and the following interaction between Ac-FOXO1
      and Atg7 regulated the basal and serum starvation (SS)-induced autophagy as
      evidenced by light chain 3 (LC3) accumulation and p62 degration. Either treatment
      with FOXO1 siRNA or resveratrol, a sirt1 agonist, inhibited autophagic flux,
      resulting in oxidative stress, mitochondrial dysfunction (MtD) and apoptosis in
      QBC939 cells, which were attenuated by enhancing autophagy with rapamycin. On the
      contrary, inhibiting autophagic flux with 3-MA worsened all these effects in
      QBC939 cells. CONCLUSIONS: Taken together, our study for the first time
      identified FOXO1 as a potential therapeutic target to cure against human
      cholangiocarcinoma via regulation of autophagy, oxidative stress and MtD.

PMID- 29466795
TI  - Dialysate Creatinine Response Patterns During Peritoneal Equilibration Test and
      the Association Between Cardiovascular Mortality: Findings from a Prospective
      Cohort Study.
AB  - BACKGROUND/AIMS: During peritoneal equilibrium test (PET), intermediate measures
      of Dt/P (dialysate/plasma creatinine ratio), D0/P, D2/P and D4/P ratios might
      provide additional information regarding a patient's cardiovascular mortality. We
      aimed to characterise heterogeneity of dialysate creatinine response patterns
      based on three ratios and compare cardiovascular mortality risks by response
      patterns. METHODS: 3,477 patients initialising peritoneal dialysis (PD) between
      2007-2015 were measured D0/P, D2/P and D4/P at baseline and 2-year cardiovascular
      mortality was defined as the primary outcome. Latent class mixed-effect models
      were fitted to identify distinct patterns of dialysate creatinine response.
      Multivariable Logistic regression model with adjustment of cardiometabolic
      factors were used to compare cardiovascular mortality by latent classes. RESULTS:
      The 1st latent class including 36% of participants was characterised by
      consistently increasing and high Dt/P ratios both at 2-hour and 4-hour. The 2nd
      class including 61% of participants characterised by sharply increased ratio at 2
      hour and slightly increased ratio at 4-hour. The 3rd class included 3% of
      participants with decreased ratio at 2-hour and increased ratio at 4-hour.
      Comparing the 1st class, the lower cardiovascular mortality risk was identified
      in the 2nd and 3rd class with adjusted odds ratio 0.65 (95% confidence interval:
      0.62-0.69) and 0.48 (0.41-0.57), respectively. CONCLUSION: Patients with
      decreased Dt/P ratio between 0-hour and 2-hour and low ratios at 2-hour and 4
      hour tend to have low cardiovascular mortality. Latent class analysis seems to be
      a promising method to reveal unidentified subgroups that do not fit into the risk
      category defined by Dt/P ratio at 4-hour.

PMID- 29466796
TI  - Changes in Dietary Patterns and the Nutritional Status in Men in the
      Metallurgical Industry in Poland Over A 21-Year Period.
AB  - BACKGROUND/AIMS: The study was carried out to evaluate the changes in the eating
      habits and lipid parameters in a 21-year follow-up on a group of 435 men living
      in Poland. METHODS: The studied population was composed of the same subjects: a
      group of men who were first studied in the years 1987-1989 and in 2008-2010. The
      following data was gathered: body mass, body mass index (BMI), total cholesterol,
      high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and
      triglyceride concentration in blood serum. RESULTS: The changes in the eating
      habits among the studied men registered throughout the 21-year period were
      positive since they showed a reduction in the caloric content of their diet (p <
      0.001), lower total fat content (p < 0.001), total amount of carbohydrates (p <
      0.001), sucrose (p < 0.001), iron (p < 0.001), and featured more vitamins: A (p <
      0.002), B1 (p < 0.001), and C (p < 0.001). An adverse trend was observed in terms
      of constant calcium shortages in their food portions (ns). A 21-year follow-up of
      the studied group showed significant differences in terms of weight (p < 0.001),
      BMI (p < 0.001), and all cholesterol fractions (p < 0.001) in their blood serum,
      except cholesterol alone (ns). CONCLUSION: It is important to continue observing
      the dietary trends in the studied group, with the focus on the occurrence of
      potential changes in their bodies.

PMID- 29466797
TI  - A Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for
      Validation of Biomarkers (PROVALID) - Study Design and Baseline Characteristics.
AB  - BACKGROUND/AIMS: The prevalence of diabetes mellitus type 2 and kidney disease in
      these patients varies widely between European countries. METHODS: In addition to
      store bio-samples the "Prospective cohort study in patients with type 2 diabetes
      mellitus for validation of biomarkers" collects information on history, physical
      status, laboratory measurements and medication in 4000 patients with diabetes
      mellitus type 2, being taken care of at the primary level of healthcare in 5
      European countries (Austria, Hungary, Netherlands, Poland and Scotland). Next to
      comparing the rate of loss of eGFR between the countries, a further objective of
      the PROVALID study is to determine the 5-year cumulative incidence of renal and
      cardiovascular outcomes. RESULTS: The mean age of the population recruited is
      62.9+/-10 years, 54.6% are male and the mean BMI is 30.9+/-5.4 kg/m2. Metabolic
      control (median HBA1c 6.8 % (6.2; 7.5)) is achieved via administration of
      metformin in 67.4% of the patients and insulin in 30.3%. Median systolic and
      diastolic blood pressure at recruitment is 135 (125; 146) and 80 (72; 85) mmHg,
      65.4% of subjects received RAAS blocking agents. Mean eGFR is 80.7+/-29.2
      ml/min/1.73m2 and median baseline albumin/creatinine ratio 8.3 mg (IQR: 3.8 and
      25.1). CONCLUSION: PROVALID will provide information on incidence and progression
      of renal and cardiovascular disease and therapy in patients with type 2 diabetes
      mellitus in different European countries. Thus, in contrast to many other cohort
      studies we will be able to associate national clinical practise pattern with
      outcome in this highly vulnerable patient population.

PMID- 29466798
TI  - Antithrombin III is a Novel Predictor for Contrast Induced Nephropathy After
      Coronary Angiography.
AB  - BACKGROUND/AIMS: Antithrombin III (AT III) is an important endogenous
      anticoagulant and has strong anti-inflammatory properties. Low ATIII activity is
      considered to be a predictor of poor outcomes in several conditions, including
      acute kidney injury after cardiac surgery. However, the association between the
      ATIII level and the occurrence of contrast induced nephropathy (CIN) has not been
      elucidated. In this study, our aim was to identify the potential predictive value
      of ATIII for CIN. METHODS: We enrolled a total of 460 patients who underwent
      coronary angiography (CAG) from January 2015 to December 2016 in coronary care
      units (CCU). ATIII activity in plasma collected before CAG was measured and <75%
      was considered low activity according to reference values. A cross-sectional
      study on CIN after CAG was conducted and the risk factors were analyzed. CIN was
      diagnosed according to the KDIGO guideline. RESULTS: Of these 460 patients
      undergoing CAG, 125 (27.17%) progressed to CIN. The incidence of CIN was
      significantly higher in patients with low ATIII activity compared to patients
      with normal ATIII activity (Pearson's chi-squared test P=0.002). As ATIII
      activity declined, the prevalence of CIN progressively increased, with the
      highest value (58.8%) in patients with an ATIII activity <60%. Moreover, the
      ATIII activity was significantly lower in CIN patients than in non-CIN patients
      (84.43+/-16.3% vs. 92.14+/-13.94%, P<0.001). After multivariable analysis, ATIII
      activity <75% remained a significant independent predictor of CIN (OR 2.207,95%CI
      [1.29-3.777]; P=0.004) as well as baseline serum creatinine (OR 1.009,95%CI
      [1.001-1.016]; P=0.026). CONCLUSIONS: Patients with low ATIII activity had a
      higher risk of developing CIN after CAG. The initial ATIII activity may be a
      novel independent predictor for CIN.

PMID- 29466799
TI  - Exogenous beta-Hydroxybutyrate Treatment and Neuroprotection in a Suckling Rat
      Model of Hypoxic-Ischemic Encephalopathy.
AB  - beta-Hydroxybutyrate (BHB) is a representative ketone body that may play a role
      in the mitigation of neonatal hypoxic-ischemic encephalopathy by altering energy
      metabolism. This study aimed to investigate the neuroprotective efficacy of
      exogenous BHB administration in a suckling rat model after hypoxia-ischemia (HI).
      Thirteen-day-old (P13) rat pups were subjected to 120 min of hypoxia according to
      the Rice-Vannucci model. BHB (5.0 mmol/kg, HI-BHB) or vehicle (0.9% saline, HI
      Veh) was administered 0, 2, 4, and 6 h after HI induction. Pathologic injury
      scores and the number of TUNEL-positive cells were evaluated on P15. Residual
      hemispheric volume was measured with T2-weighted MRI (on P27) and functional
      tests, such as the negative geotaxis test, rope suspension test, rotarod test,
      novel object recognition test, and cylinder test, were performed. Systemic
      ketosis (approx. 2.0-3.0 mM/L) was well tolerated by the rat pups with no
      difference in the mortality rate between both groups. Compared with the HI-Veh
      group, the HI-BHB group demonstrated significantly lower pathological scores as
      well as fewer TUNEL-positive cells. The intact residual hemispheric and
      hippocampal volumes were greater in the HI-BHB group than the HI-Veh group.
      However, the results of functional tests did not differ between both groups.
      Postischemic BHB administration reduced brain injury in suckling rats after HI.
      The safe clinical application of our animal model to human infants with HI
      requires further investigation.

PMID- 29466800
TI  - The Association Between Oxidative Stress Alleviation via Sulforaphane-Induced
      Nrf2-HO-1/NQO-1 Signaling Pathway Activation and Chronic Renal Allograft
      Dysfunction Improvement.
AB  - BACKGROUND/AIMS: Chronic renal allograft dysfunction (CRAD) is a leading cause of
      long-term renal allograft loss. Oxidative stress may account for the nonspecific
      interstitial fibrosis and tubular atrophy that occur in CRAD. An antioxidant
      intervention via Nrf2 signaling pathway activation might be a promising therapy
      for some kidney diseases. The present paper investigates whether there is an
      association between oxidative stress alleviation via sulforaphane-induced Nrf2-HO
      1/NQO-1 signaling pathway activation and CRAD improvement. METHODS: F344 rat
      kidneys were orthotopically transplanted into Lewis rat recipients to establish
      CRAD models. Sulforaphane was administered at 1.5 mg/kg intraperitoneally once
      daily. Renal function and 24-hour urinary protein were monitored for variations
      for 24 weeks after transplantation. After 24 weeks, renal histopathology was
      evaluated according to the Banff criteria after hematoxylin and eosin, Masson's
      trichrome and periodic acid-Schiff stainings. Additionally, intrarenal oxidative
      stress was assessed by the indicators malondialdehyde, 8-isoprostane, oxidized
      low density lipoprotein and 8-hydroxy-2'-deoxyguanosine, as well as the activity
      levels of the antioxidant enzymes total superoxide dismutase, catalase,
      glutathione peroxidase, glutathione reductase and gamma-glutamylcysteine
      synthetase. Nrf2, HO-1 and NQO-1 expression levels were determined via
      immunohistochemical and Western blot analyses. RESULTS: The sulforaphane-induced
      Nrf2-HO-1/NQO-1 signaling pathway activation, as demonstrated by
      immunohistochemical and Western blot analyses, delayed the progression of serum
      creatinine and blood urea nitrogen, particularly lowering the 24-hour urinary
      protein levels of CRAD. The semi-quantified histopathological changes were also
      alleviated. Evidence of oxidative stress alleviation, as indicated by a
      concurrent decrease in the indicators and sustained levels of antioxidant enzymes
      activity, was found in the renal allografts after sulforaphane intervention.
      CONCLUSION: Oxidative stress alleviation caused by continuous sulforaphane
      induced Nrf2-HO-1/NQO-1 signaling pathway activation is associated with
      functional and morphological improvements of CRAD.

PMID- 29466801
TI  - Benzodiazepines as a Monotherapy in Depressive Disorders: A Systematic Review.
AB  - BACKGROUND: The aim of this paper was to perform a systematic review and, when
      feasible, a meta-analysis of randomized controlled trials (RCT) which used
      benzodiazepines (BZD) as a monotherapy versus placebo, antidepressant drugs (AD),
      or both. METHODS: Keyword searches were conducted for identifying RCT comparing
      BZD and AD, and/or placebo in the treatment of depression, using electronic
      databases from their inception up to April 2017. We selected reports of RCT in
      which BZD were compared to AD and/or placebo in the treatment of adult patients
      with a primary diagnosis of depressive disorder or anxious depression. When
      feasible, data were subjected to meta-analysis. RESULTS: A total of 38 studies
      met the criteria for inclusion and were then included in the systematic review.
      Only 1 study concerned a newer AD, fluvoxamine. For the meta-analysis, we
      submitted data on response rate from 22 RCT, considering BZD versus placebo (8
      comparisons) and BZD versus tricyclic antidepressants (TCA) (20 comparisons).
      There was a lack of significant differences as to response rate between BZD and
      placebo, as well as between BZD and TCA. Analysis of individual studies disclosed
      that, in more than half of the studies comparing BZD to TCA and/or placebo, BZD
      were significantly more effective than placebo and as effective as TCA.
      CONCLUSIONS: BZD are a therapeutic option in anxious depression and there are no
      indications that AD are preferable. There is a pressing need for RCT of adequate
      methodological quality and follow-up comparing BZD to second-generation AD and
      placebo in anxious depression.

PMID- 29466802
TI  - Healthy and Pathological Brain Aging: From the Perspective of Oscillations,
      Functional Connectivity, and Signal Complexity.
AB  - Healthy aging is associated with impairment in cognitive information processing.
      Several neuroimaging methods such as functional magnetic resonance imaging,
      positron emission tomography and near-infrared spectroscopy have been used to
      explore healthy and pathological aging by relying on hemodynamic or metabolic
      changes that occur in response to brain activity. Since electroencephalography
      (EEG) and magnetoencephalography (MEG) are able to measure neural activity
      directly with a high temporal resolution of milliseconds, these
      neurophysiological techniques are particularly important to investigate the
      dynamics of brain activity underlying neurocognitive aging. It is well known that
      age is a major risk factor for Alzheimer's disease (AD), and that synaptic
      dysfunction represents an early sign of this disease associated with hallmark
      neuropathological findings. However, the neurophysiological mechanisms underlying
      AD are not fully elucidated. This review addresses healthy and pathological brain
      aging from a neurophysiological perspective, focusing on oscillatory activity
      changes during the resting state, event-related potentials and stimulus-induced
      oscillatory responses during cognitive or motor tasks, functional connectivity
      between brain regions, and changes in signal complexity. We also highlight the
      accumulating evidence on age-related EEG/MEG changes and biological markers of
      brain neurodegeneration, including genetic factors, structural abnormalities on
      magnetic resonance images, and the biochemical changes associated with Abeta
      deposition and tau pathology.

PMID- 29466803
TI  - Grandiose and Vulnerable Narcissism in Borderline Personality Disorder.
AB  - BACKGROUND: Little is known about narcissistic traits in borderline personality
      disorder (BPD). This exploratory study aimed to illustrate the associations
      between total, grandiose, and vulnerable narcissism and gender, diagnostic
      features of BPD and narcissistic personality disorder (NPD), and psychopathology
      in BPD patients. SAMPLING AND METHODS: The Pathological Narcissism Inventory and
      psychometric measures for impulsivity, anger, borderline symptom severity,
      personality organization, depression, and rejection sensitivity were completed by
      65 BPD patients. Statistical analyses were conducted using the t test, Pearson
      correlation, and multivariate regression analyses. RESULTS: Male BPD patients
      displayed higher narcissistic scores than females (p < 0.01). Grandiose
      narcissism showed a stronger association with NPD than with BPD (p < 0.01) while
      vulnerable narcissism was only associated with BPD (p < 0.01). Rejection
      sensitivity (p < 0.01) and depression (p < 0.001) predicted vulnerable
      narcissism. CONCLUSION: Vulnerable narcissism is closely associated with BPD and
      appears to be more dysfunctional than grandiose narcissism. A comprehensive
      consideration of both traits is recommended. Our results might help to generate
      hypotheses for further research on pathological narcissism in the spectrum of
      personality disorders. Future studies are advised to apply complementary measures
      and take new diagnostic approaches of DSM-5 and ICD-11 into account.

PMID- 29466804
TI  - Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to
      the S170F Mutation of Presenilin-1.
AB  - BACKGROUND: In rare cases, patients with Alzheimer disease (AD) present at an
      early age and with a family history suggestive of an autosomal dominant mode of
      inheritance. Mutations of the presenilin-1 (PSEN1) gene are the most common
      causes of dementia in these patients. Early-onset and particularly familial AD
      patients frequently present with variable non-amnestic cognitive symptoms such as
      visual, language or behavioural changes as well as non-cognitive, e.g. motor,
      symptoms. OBJECTIVE: To investigate the phenotypic variability in carriers of the
      PSEN1 S170F mutation. METHODS: We report a family with 4 patients carrying the
      S170F mutation of whom 2 underwent detailed clinical examinations. We discuss our
      current findings in the context of previously reported S170F cases. RESULTS: The
      clinical phenotype was consistent regarding initial memory impairment and early
      onset in the late twenties found in all S170F patients. There were frequent non
      amnestic cognitive changes and, at early stages of the disease, indications of a
      more pronounced disturbance of visuospatial abilities as compared to face and
      object recognition. Non-cognitive symptoms most often included myoclonus and
      cerebellar ataxia. A review of the available case reports indicates some
      phenotypic variability associated with the S170F mutation including different
      constellations of symptoms such as parkinsonism and delusions. CONCLUSION: The
      variable clinical findings associated with the S170F mutation highlight the
      relevance of atypical phenotypes in the context of research and under a clinical
      perspective. CSF sampling and detection of Abeta species may be essential to
      indicate AD pathology in unclear cases presenting with cognitive and motor
      symptoms at a younger age.

PMID- 29466805
TI  - Personality Disorder and Alcohol Use Disorder: An Overview.
AB  - BACKGROUND: Clinically, personality disorder (PD) commonly coexists with alcohol
      use disorder (AUD), although within mainstream mental health services both of
      these mental disorders are routinely overlooked. Despite a rich literature
      examining the interactions between AUD and personality functioning, personality
      traits, and PD, there remains conflicting evidence as to the degree of
      association and impact of one on the other. METHODS: A narrative review and a
      synthesis of the literature were done. RESULTS: The lifetime prevalence of AUD
      approaches 50% in some PD populations. The rates of PD in AUD populations are
      less clear but likely similar. Personality influences outcomes in AUD regardless
      of whether a categorical personality diagnosis or dimensional trait domain
      approach is taken. There are, however, no good data to inform clinicians on the
      impact of AUD on the outcomes of PD. Understanding the extent of this impact is
      complicated by the multiple tools used for diagnosis (of both PD and AUD) and the
      statistical methods used. Overall, caution is required in interpreting the data
      due to the quality of the current literature; however, comorbidity between the
      two disorders is likely significant and the impact of PD on AUD outcomes is
      sufficient to require consideration. CONCLUSIONS: From a research perspective,
      better agreement on both diagnoses and outcomes is urgently needed to improve the
      overall quality of the evidence. Clinically, despite the limitations in the
      literature, it is unacceptable for PD services to ignore AUD and for AUD services
      not to screen for PD. Both are likely to have an impact on health and functioning
      and should be considered in routine reviews. A better conceptualization of the
      putative mechanisms of this interaction, as well as an understanding of the
      neurobiology and reasons for the impact on treatment outcomes, will help to move
      the field forward.

PMID- 29466806
TI  - Vitamin D and Its Role in Neonatal Hypoxic-Ischemic Brain Injury.
AB  - Emerging evidence has demonstrated that vitamin D plays an important role in many
      adult neurologic disorders, but is also critical in neuronal development and
      pruning in the neonatal and pediatric populations. Neonates are at a particularly
      high risk of vitamin D deficiency, in part due to the high prevalence of maternal
      deficiency during pregnancy. Several preclinical studies have demonstrated that
      infants born to vitamin D-deficient mothers are at a high risk of developing
      neonatal brain injury, and recent clinical studies have shown that neonates with
      hypoxic-ischemic encephalopathy (HIE) tend to be vitamin D-deficient. There are
      limited data, however, on whether additional prenatal or postnatal
      supplementation may alter the prevalence or severity of neonatal HIE. This review
      examines the current data supporting the neuroprotective role of vitamin D, with
      a focus on how these findings may be translated to neonates with HIE.

PMID- 29466807
TI  - Sutureless Belt Loops versus Sutured Buckle Technique in Combination with
      Vitrectomy for Retinal Detachment Repair: A Comparative Analysis.
AB  - OBJECTIVE: To compare the anatomic and visual outcomes in primary rhegmatogenous
      retinal detachment repair involving combined pars plana vitrectomy (PPV)/scleral
      buckle (SB) using a sutureless belt loops technique versus a conventional sutured
      buckle technique. METHODS: This is a retrospective, consecutive, interventional,
      comparative case series study using patients treated for primary retinal
      detachment who underwent the SB procedure in combination with PPV. Details
      regarding anatomic and visual outcome were analyzed. RESULTS: Thirty-five eyes
      were included in this study: 18 eyes (18 patients) treated with combined PPV and
      SB performed using a sutureless belt loops technique (group A) and 17 eyes (17
      patients) treated with combined PPV and SB sutured to the sclera (group B).
      Successful anatomic attachment and appropriate buckle height were achieved in all
      35 cases. There was 1 case of redetachment in each group during the follow-up:
      1/17 (5.9%) in group A and 1/18 (5.6%) in group B (p = 0.97). No cases of buckle
      infection, extrusion, or intrusion were noted during the follow-up period.
      CONCLUSION: SBs installed using a belt loops sutureless technique appear to be as
      safe and effective as those applied using conventional suturing for repair of
      retinal detachment, with similar anatomic and functional outcomes.

PMID- 29466808
TI  - Impact of Green Tea Catechin ECG and Its Synthesized Fluorinated Analogue on
      Prostate Cancer Cells and Stimulated Immunocompetent Cells.
AB  - Among the known or suspected risk factors, inflammation plays an important role
      in infectious and non-infectious pathways leading to cancer. Green tea
      polyphenols have been associated with reducing inflammation and protection
      against carcinogenesis, especially in prostate cancer. While most of the research
      in this field, so far, has focussed on epigallocatechin-3-O-gallate only, we
      studied epicatechin-3-O-gallate, the second most abundant green tea polyphenol
      with essential therapeutic potential, to obtain a more detailed understanding of
      its anti-tumor and anti-inflammatory action. Furthermore, to improve the
      bioactivity of (-)-epicatechin-3-O-gallate, we synthesized a difluoro analogue,
      called (-)-5,7-difluoro-epicatechin-3-O-gallate. Both compounds reduced cell
      proliferation of human primary inflammatory lymphocytes in an apoptosis-specific
      fashion, while (-)-5,7-difluoro-epicatechin-3-O-gallate had a significantly
      higher activity compared to the natural product (-)-epicatechin-3-O-gallate.
      Treatment of low-metastatic LNCaP and high-metastatic PC-3 prostate cancer cells
      with (-)-epicatechin-3-O-gallate and (-)-5,7-difluoro-epicatechin-3-O-gallate
      demonstrated a dose-dependent inhibition of cell viability in the low micromolar
      range. These effects suggest that (-)-epicatechin-3-O-gallate and the more
      effective (-)-5,7-difluoro-epicatechin-3-O-gallate could be therapeutically used
      to inhibit tumorigenesis during initiation, promotion, and progression by
      diminishing the amount of inflammation due to a reduction of inflammatory
      lymphocytes. Further studies are needed to prove this in in vivo experiments.

PMID- 29466809
TI  - An Update on the Biological Activities of Euterpe edulis (Jucara).
AB  - The palm tree Euterpe edulis, known as jucara, produces spherical and purple
      fruits, similar to those of the Euterpe oleracea and Euterpe precatoria palm
      trees, from which the common name acai originates. Jucara fruit has been gaining
      prominence in the scientific world for its interesting nutritional composition,
      which is rich in antioxidants, and for its sustainable production model.
      Recently, relevant biological activities have been associated with the jucara
      fruit, and its use in alimentation has become an important nutritional,
      environmental, and economic alternative. The aim of this review is to compile
      recent scientific data about the phytochemical characterization and biological
      activities of E. edulis. A review of the literature was conducted in two
      electronic databases, Medline and Science Direct. The eligibility criteria were
      as follows: phytochemicals characterize of the E. edulis fruits and evaluate
      biological effects in vitro or in vivo with pulp, extract, juice, or product of
      jucara fruits. Investigations were excluded if they used other parts of the plant
      (seeds), did not assess biological activities, or have tested methodologies for
      compound extraction. From the identified reports, 25 articles were eligible for
      this study. The promotion of health benefits related to jucara fruits seems to
      have improved antioxidant activity in vivo, benefits to lipid and glycemic
      profiles, and modulation of inflammatory status in experimental studies in
      animals.

PMID- 29466810
TI  - Three-Dimensional Printed Facial Models in Rhinoplasty.
AB  - Digital patient photography and morphing software have become an important part
      of rhinoplasty over the past few decades. Presented is a novel technology
      incorporating 3D photography and printing to produce life-size models for use in
      patient evaluation and treatment. Surveys were conducted to assess patient
      response and were universally positive. Early surgeon experience also indicates
      benefit for intraoperative use. Three-dimensional printing and modeling is a new
      technology that has exciting applications for rhinoplasty and facial plastic
      surgery.

PMID- 29466811
TI  - Facial Asymmetry: Brow and Ear Position.
AB  - The purpose of the current study was to analyze brow and ear position, and
      examine the relationship between these structures in patients presenting for
      blepharoplasty evaluation. A retrospective chart review was performed, which
      included all patients presenting to one oculoplastic physician for a
      blepharoplasty evaluation from November, 2012 to March, 2014. The prevalence of
      brow ptosis and brow and ear asymmetry was calculated; the proportional
      distribution was determined, and chi-square analysis and the z-test of
      proportions were used to calculate the significance. Institutional Review Board
      approval was obtained for this study. A total of 133 patients met the inclusion
      criteria. Some degree of brow ptosis was noted in 83% of patients. Brow asymmetry
      was found in 88% of patients, and ear asymmetry in 77%. Of those patients who had
      asymmetry, 61% had the right brow lower and 75% had the right ear lower; 73% of
      all patients had the brow and ear lower on the same side (p < 0.001). In this
      study, brow ptosis and asymmetry were quite common. In addition, the side of the
      lower brow correlated strongly with the side of the lower ear, and the right side
      structures were lower more often than the left. Patients presenting for
      blepharoplasty evaluation may have an element of generalized facial asymmetry
      which includes the brows and ears. These observations can be important for
      preoperative planning and patient counseling.

PMID- 29466812
TI  - [Non-Small Cell Lung Cancer - Development of Parallel Mechanisms of Resistance].
AB  - Acquired resistances to tyrosine kinase inhibitors in non-small cell lung cancer
      develop after 9 - 12 month. In 60 % of the cases these resistances arise because
      of a secondary EGFR-T790 M resistance mutation. This report is describing the
      case of a patient who developed parallel two different mechanisms of resistance:
      A T790 M resistance mutation and a transformation into a small cell
      neuroendocrine cancer. Under therapy with Osimertinib and chemotherapy with
      carboplatin and etoposide the tumor responsed partially.

PMID- 29466813
TI  - [Grand Duchess Alexandra Nikolajewna Romanowa].

PMID- 29466815
TI  - Clip-fixed endoloop: an efficacious new method for mucosal defect closure.

PMID- 29466814
TI  - [DGP Interstitial Lung Disease Patient Questionnaire].
AB  - BACKGROUND:  Interstitial lung diseases (ILD) encompass different heterogeneous,
      mainly chronic diseases of the pulmonary interstitium and/or alveoli with known
      and unknown reasons. The diagnostic of ILD is challenging and should be performed
      interdisciplinary. The medical history is of major importance and therefore, in
      German-speaking countries the Frankfurter Bogen (published in 1985) was utilised
      to scrutinise the medical history of the patient. This by now more than 30-years
      old questionnaire requires a revision with regard to content and language.
      METHOD:  Under the auspices of the clinical section of the DGP the new
      Interstitial Lung Disease Patient Questionnaire was developed in collaboration
      amongst pulmonologist, occupational medicine physicians and psychologists and
      supported by patient support groups. The questionnaire was finally optimised
      linguistically with the help of patients. RESULTS:  The newly developed patient
      questionnaire for interstitial and rare lung diseases encompasses different
      domains: initial and current symptoms, medical history questions including prior
      drug treatments, previous pulmonary and extrapulmonary diseases, potential
      exposition at home, work and leisure time as well as family history and
      travelling. CONCLUSION:  The newly developed questionnaire can facilitate the
      diagnosis in patients with suspicion on interstitial lung disease in clinical
      routine.

PMID- 29466816
TI  - Endoscopic transmural hydro-dissection as a rescue therapy for rectal fibrotic
      adenoma.

PMID- 29466817
TI  - Endoscopic removal of two magnets impacted in the lower esophagus and gastric
      fundus.

PMID- 29466818
TI  - Development and Validation of a Natural Language Processing Tool to Identify
      Patients Treated for Pneumonia across VA Emergency Departments.
AB  - BACKGROUND: Identifying pneumonia using diagnosis codes alone may be insufficient
      for research on clinical decision making. Natural language processing (NLP) may
      enable the inclusion of cases missed by diagnosis codes. OBJECTIVES: This article
      (1) develops a NLP tool that identifies the clinical assertion of pneumonia from
      physician emergency department (ED) notes, and (2) compares classification
      methods using diagnosis codes versus NLP against a gold standard of manual chart
      review to identify patients initially treated for pneumonia. METHODS: Among a
      national population of ED visits occurring between 2006 and 2012 across the
      Veterans Affairs health system, we extracted 811 physician documents containing
      search terms for pneumonia for training, and 100 random documents for validation.
      Two reviewers annotated span- and document-level classifications of the clinical
      assertion of pneumonia. An NLP tool using a support vector machine was trained on
      the enriched documents. We extracted diagnosis codes assigned in the ED and upon
      hospital discharge and calculated performance characteristics for diagnosis
      codes, NLP, and NLP plus diagnosis codes against manual review in training and
      validation sets. RESULTS: Among the training documents, 51% contained clinical
      assertions of pneumonia; in the validation set, 9% were classified with
      pneumonia, of which 100% contained pneumonia search terms. After enriching with
      search terms, the NLP system alone demonstrated a recall/sensitivity of 0.72
      (training) and 0.55 (validation), and a precision/positive predictive value (PPV)
      of 0.89 (training) and 0.71 (validation). ED-assigned diagnostic codes
      demonstrated lower recall/sensitivity (0.48 and 0.44) but higher precision/PPV
      (0.95 in training, 1.0 in validation); the NLP system identified more "possible
      treated" cases than diagnostic coding. An approach combining NLP and ED-assigned
      diagnostic coding classification achieved the best performance (sensitivity 0.89
      and PPV 0.80). CONCLUSION: System-wide application of NLP to clinical text can
      increase capture of initial diagnostic hypotheses, an important inclusion when
      studying diagnosis and clinical decision-making under uncertainty.

PMID- 29466820
TI  - [Not Available].

PMID- 29466819
TI  - Feasibility Testing of a Wearable Behavioral Aid for Social Learning in Children
      with Autism.
AB  - BACKGROUND: Recent advances in computer vision and wearable technology have
      created an opportunity to introduce mobile therapy systems for autism spectrum
      disorders (ASD) that can respond to the increasing demand for therapeutic
      interventions; however, feasibility questions must be answered first. OBJECTIVE:
      We studied the feasibility of a prototype therapeutic tool for children with ASD
      using Google Glass, examining whether children with ASD would wear such a device,
      if providing the emotion classification will improve emotion recognition, and how
      emotion recognition differs between ASD participants and neurotypical controls
      (NC). METHODS: We ran a controlled laboratory experiment with 43 children: 23
      with ASD and 20 NC. Children identified static facial images on a computer screen
      with one of 7 emotions in 3 successive batches: the first with no information
      about emotion provided to the child, the second with the correct classification
      from the Glass labeling the emotion, and the third again without emotion
      information. We then trained a logistic regression classifier on the emotion
      confusion matrices generated by the two information-free batches to predict ASD
      versus NC. RESULTS: All 43 children were comfortable wearing the Glass. ASD and
      NC participants who completed the computer task with Glass providing audible
      emotion labeling (n = 33) showed increased accuracies in emotion labeling, and
      the logistic regression classifier achieved an accuracy of 72.7%. Further
      analysis suggests that the ability to recognize surprise, fear, and neutrality
      may distinguish ASD cases from NC. CONCLUSION: This feasibility study supports
      the utility of a wearable device for social affective learning in ASD children
      and demonstrates subtle differences in how ASD and NC children perform on an
      emotion recognition task.

PMID- 29466821
TI  - [The Update of the Rehabilitation Therapy Standards of the German Pension
      Assurance].
AB  - OBJECTIVES: To report on the process of updating the German Pension Insurers'
      rehabilitation therapy standards (RTS) from 2013 to 2015. METHODS: Four
      methodical approaches were taken to gather evidence: a) systematic literature
      searches, b) the formation of expert groups, expert workshops, and online
      discussion forums to bring together the experiences from clinicians and patients,
      c) an analysis of the latest KTL data to understand the extent to which the RTS
      are currently being fulfilled, and d) conceptual consideration of the
      significance of current developments in rehabilitation in light of the RTS
      revision. RESULTS: There are now updated versions of all 9 RTS. Over half of the
      therapy modules are based on scientific evidence. Other modules are based on
      clinical experience with good clinical-practice standards. The scientific
      evidence has not changed much overall in the last few years, although there are
      some indications of higher evidence levels. CONCLUSION: The revised RTS can make
      a positive contribution to ensuring that rehabilitation is of high quality.
      Further research is needed to increase the level of evidence - especially
      regarding the intensity of therapy.

PMID- 29466823
TI  - Analytical and Pharmacological Challenges in Cannabis Research.

PMID- 29466822
TI  - ?
AB  - Alternative diets (AD) differ from the current common mixed diet; AD are
      recommended as a permanent diet. These diets are based on ethical, philosophical
      and health promoting principles and lead to very different recommendations for
      food selection. Even within a particular AD there is usually a broad spectrum of
      versions, so that a general evaluation is only possible to a limited extent. This
      is also true for single AD. Vegetarian diets and partly paleo-diets have been
      investigated to a reasonable extent. Plant based diets are appropriate as
      permanent diets and offer health benefits as compared with currently practiced
      diets (risk reduction of cancers by 10-18% and of heart diseases by 30%;
      favorable effect on blood pressure and lipid profile; no risk reduction on cancer
      and total mortality). Vegan diets have to be critically assessed: they are linked
      to an increased risk of deficits for single nutrients (vitamin B12, iodine and as
      the case may be. calcium and long chain omega-3 fatty acids), if suitable
      supplements or fortified foods are not consumed.

PMID- 29466824
TI  - QTc Time Correlates with Amitriptyline and Venlafaxine Serum Levels in Elderly
      Psychiatric Inpatients.
AB  - INTRODUCTION: Many antidepressants cause QT prolongation but the classification
      of cardiac risk of these drugs varies markedly in different published lists. This
      retrospective study analyzed the correlation of QTc time with amitriptyline and
      venlafaxine serum level in elderly psychiatric inpatients. METHODS: Elderly
      inpatients aged>=65 years for whom venlafaxine or amitriptyline serum level had
      been measured were selected retrospectively from a therapeutic drug monitoring
      database and screened for an electrocardiogram measurement at the time of blood
      withdrawal. The correlation of amitriptyline or venlafaxine serum levels with QTc
      time was examined by using Pearson's correlation analysis. RESULTS: Amitriptyline
      serum levels (n=11) correlated significantly with QTc time (r=0.918, p<0.001, CI
      95%). Venlafaxine serum levels (n=27) also correlated significantly with QTc time
      (r=0.382, p<0.05, CI 95%). DISCUSSION: Amitriptyline and venlafaxine induce QT
      prolongation depending on drug concentrations in blood. Its extent, however, is
      very low when drug serum levels are within the therapeutic range. Future
      pharmacokinetic studies that correlate drug serum level and QT time should
      classify the cardiac risk of drugs based on the grade of the regression line in
      relation to the therapeutic range.

PMID- 29466825
TI  - Responses to warnings about the impact of eating disorders on fertility: a
      qualitative study.
AB  - Eating disorders (EDs) have often been discussed as a risk to reproductive
      health. But existing research is quantitative in nature, paying no attention to
      issues of patient experience. In discussing data from 24 semi-structured
      interviews, this article draws on sociological approaches to medical 'risk' and
      feminist approaches to EDs to explore how women with experience of an ED
      responded to fertility warnings within treatment contexts. In doing so, it is
      suggested that responses to fertility warnings offer unique insight into the
      potentially damaging limitations of biomedical approaches to eating problems and
      their focus on EDs as individual 'pathologies' (rather than culturally embedded
      expressions of gendered embodiment). At best warnings are seen as making
      problematic assumptions about the aspirations of female patients, which may
      curtail feelings of agency and choice. At worst, they may push women further into
      destructive bodily and eating practices, and silence the distress that may be
      articulated by an ED.

PMID- 29466826
TI  - Therapeutic effect of microcurrent on calf muscle atrophy in immobilized rabbit.
AB  - INTRODUCTION: Immobilization causes significant muscle loss. In this study we
      assessed the regenerative effect of microcurrent electrical stimulation (MES) on
      gastrocnemius muscle (GCM) atrophy induced by immobilization by cast (IC) in
      rabbits. METHODS: Fifteen rabbits were divided into 3 groups: IC (group 1); IC
      and free re-ambulation for 2 weeks after cast removal (CR) (group 2); and IC and
      MES for 2 weeks after CR (group 3). We evaluated clinical parameters (calf
      circumference, compound muscle action potential of tibial nerve, and thickness of
      GCM by ultrasound), histomorphometric data (muscle composition and cross
      sectional area), and immunohistochemistry. RESULTS: Mean atrophic changes in
      clinical parameters in group 3 were significantly less than those in groups 1 and
      2 (P < 0.05). Histomophometric and immunohistochemical parameters in group 3 were
      significantly greater than those in groups 1 and 2, respectively (P < 0.05).
      DISCUSSION: MES prevents muscle atrophy and facilitates regeneration of muscle.
      Muscle Nerve 58: 270-276, 2018.

PMID- 29466828
TI  - Nerve conduction study of the three supraclavicular nerve branches.
AB  - INTRODUCTION: We describe a new nerve conduction study technique with reference
      values for the 3 branches of the supraclavicular nerve (SCN) in young healthy
      subjects and application of it in 2 patients. METHODS: The recording electrode
      was placed on the posterior border of the sternocleidomastoid muscle, 6-7 cm from
      the sternoclavicular joint. SCN branches were stimulated below the clavicle, 2.5,
      7, and 10.5 cm lateral to the sternoclavicular joint. RESULTS: Twenty healthy
      volunteers (10 men), 19-38 years, mean 25.9 years (SD 6.3), and 2 patients with
      SCN lesions were studied. The mean conduction velocities of the SCN branches were
      70-78 m/s (SD 8-10 m/s), and amplitudes 3-4 uV (SD 0.9-2.0 uV). There were no
      side-to-side or gender differences. DISCUSSION: The 3 SCN branches could be
      studied in all subjects. We provide reference values for young subjects. This new
      method was useful in verifying SCN lesions in 2 patients. Muscle Nerve 58: 300
      303, 2018.

PMID- 29466827
TI  - Psychometric analysis of the pediatric quality of life inventory 3.0
      neuromuscular module administered to patients with duchenne muscular dystrophy: A
      rasch analysis.
AB  - INTRODUCTION: Our objective in this study was to assess the psychometric
      properties of the English (UK and USA) version of the Pediatric Quality of Life
      Inventory 3.0 Neuromuscular Module (PedsQL NMM) administered to patients with
      Duchenne muscular dystrophy (DMD). METHODS: Patients with DMD from the UK and the
      US completed the PedsQL NMM online. The psychometric properties of the instrument
      were examined using Rasch analysis. RESULTS: A total of 278 patients completed
      the PedsQL NMM. Model misfit was identified for 6 of 25 items (item fit residual:
      mean 0.162, standard deviation [SD] 2.333), 22 of 25 items displayed disordered
      thresholds, and item dependency was high. The mean person fit residual was
      estimated at -0.183 (SD 1.475). The Person Separation Index and Cronbach's alpha
      were estimated at 0.904 and 0.915, respectively. DISCUSSION: The English version
      of the PedsQL NMM may not be a valid measure of health-related quality of life in
      patients with DMD. Muscle Nerve 58: 367-373, 2018.

PMID- 29466829
TI  - Gender and quality of life in myasthenia gravis patients from the myasthenia
      gravis foundation of America registry.
AB  - INTRODUCTION: Quality of life (QOL) has been poorly characterized among patients
      with myasthenia gravis (MG) other than assessments performed within the clinical
      setting. METHODS: Patients age >= 18 years who were diagnosed with MG and
      registered with the MG patient registry between July 1, 2013, and June 30, 2016,
      were included. Demographic information, disease related history, and QOL were
      compared between men and women using multivariable analysis. RESULTS: A total of
      1,315 subjects (827 women) were included. Women were significantly younger, had a
      younger age at symptom onset, and were more likely to have thymoma and
      thymectomy. The 15-item Myasthenia Gravis Quality of Life scale (MG-QOL15) was
      significantly worse in women. MG-QOL15 score was comparable between women who had
      thymectomy and men with or without thymectomy. DISCUSSION: QOL among MG patients
      is worse in women compared with men, but this disparity is eliminated in women
      who have undergone thymectomy. Muscle Nerve, 2018.

PMID- 29466831
TI  - The diminishing role of liver biopsy in living donor liver transplantation.

PMID- 29466830
TI  - Correlating serum micrornas and clinical parameters in amyotrophic lateral
      sclerosis.
AB  - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a debilitating neurologic
      disorder with poor survival rates and no clear biomarkers for disease diagnosis
      and prognosis. METHODS: We compared serum microRNA (miRNA) expression from
      patients with ALS with healthy controls and patients with multiple sclerosis and
      Alzheimer disease. We also correlated miRNA expression in cross-sectional and
      longitudinal cohorts of ALS patients with clinical parameters. RESULTS: We
      identified 7 miRNAs (miR-192-5p, miR-192-3p, miR-1, miR-133a-3p, miR-133b, miR
      144-5p, miR-19a-3p) that were upregulated and 6 miRNAs (miR-320c, miR-320a, let
      7d-3p, miR-425-5p, miR-320b, miR-139-5p) that were downregulated in patients with
      ALS compared with healthy controls, patients with Alzheimer disease, and patients
      with multiple sclerosis. Changes in 4 miRNAs (miR-136-3p, miR-30b-5p, miR-331-3p,
      miR-496) correlated positively and change in 1 miRNA (miR-2110) correlated
      negatively with changes in clinical parameters in longitudinal analysis.
      DISCUSSION: Our findings identified serum miRNAs that can serve as biomarkers for
      ALS diagnosis and progression. Muscle Nerve 58: 261-269, 2018.

PMID- 29466832
TI  - Pathogen spillover during land conversion.
AB  - Pathogen spillover from wildlife to domestic animals and humans, and the reverse,
      has caused significant epidemics and pandemics worldwide. Although pathogen
      emergence has been linked to anthropogenic land conversion, a general framework
      to disentangle underlying processes is lacking. We develop a multi-host model for
      pathogen transmission between species inhabiting intact and converted habitat.
      Interspecies contacts and host populations vary with the proportion of land
      converted; enabling us to quantify infection risk across a changing landscape. In
      a range of scenarios, the highest spillover risk occurs at intermediate levels of
      habitat loss, whereas the largest, but rarest, epidemics occur at extremes of
      land conversion. This framework provides insights into the mechanisms driving
      disease emergence and spillover during land conversion. The finding that the risk
      of spillover is highest at intermediate levels of habitat loss provides important
      guidance for conservation and public health policy.

PMID- 29466833
TI  - Valve-sparing reimplantation for neoaortic root dilatation and regurgitation with
      an unbalanced cusp after the arterial switch operation.
AB  - A 13-year-old male presented with neoaortic root dilatation and severe aortic
      valve regurgitation 13 years following an arterial switch operation. The valve
      cusps were unbalanced due to an enlarged non-coronary cusp. A valve-sparing
      reimplantation with a cusp plication was performed which resulted in a competent
      valve with trivial regurgitation. Thus, even in an unbalanced cusp, valve-sparing
      reimplantation can be used for neoaortic root dilatation and valve regurgitation
      after an arterial switch operation.

PMID- 29466834
TI  - Central and Peripheral Expression of DNA Double-Strand Breaks in Human and Mouse
      Tissues.
AB  - Mammalian cells accumulate DNA lesions when they undergo phases of the cell cycle
      or during normal cellular activity. In this regard, several DNA repair signaling
      pathways have evolved to maintain genome stability and avoid the potential
      acquisition of mutations. To define and further characterize the expression of
      DNA double-strand breaks in humans and mice, we used immunocytochemistry to
      localize a DNA damage signal within the spatial confines of the cell nucleus. We
      show that DNA double-strand breaks are abundantly expressed in postmitotic
      neurons of the human and mouse brain. Notably, DNA double-strand breaks are
      present in human hypothalamic and mouse striatal and hippocampal cells, with
      stable expression of the nuclear signal detected throughout the mammalian brain.
      Analysis of the mouse tongue, heart, and testis shows that expression of DNA
      double-strand breaks is only demonstrated in circumscribed populations of
      peripheral cells. These data suggest that levels of DNA double-strand breaks are
      tissue-specific with the tongue, heart and testicular tissue having different
      thresholds of DNA repair and DNA damage from those outlined at the brain level.
      Anat Rec, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29466835
TI  - Aortic retrograde type A aortic dissection following repair of a thoraco
      abdominal aortic aneurysm.

PMID- 29466836
TI  - TGFbeta1-induced expression of caldesmon mediates epithelial-mesenchymal
      transition.
AB  - Epithelial-mesenchymal transition (EMT) is an important process that mediates
      organ development and wound healing, and in pathological contexts, it can
      contribute to the progression of fibrosis and cancer. During EMT, cells exhibit
      marked changes in cytoskeletal organization and increased expression of a variety
      of actin associated proteins. Here, we sought to determine the role of caldesmon
      in mediating EMT in response to transforming growth factor (TGF)-beta1. We find
      that the expression level and phosphorylation state of caldesmon increase as a
      function of time following induction of EMT by TGFbeta1 and these changes in
      caldesmon correlate with increased focal adhesion number and size and increased
      cell contractility. Knockdown and forced expression of caldesmon in epithelial
      cells reveals that caldesmon expression plays an important role in regulating the
      expression of the myofibroblast marker alpha smooth muscle actin. Results from
      these studies provide insight into the role of cytoskeletal associated proteins
      in the regulation of EMT and may suggest ways to target the cell cytoskeleton for
      regulating EMT processes.

PMID- 29466838
TI  - Updated Hepatitis B Guidance: Implications for liver transplant patients.

PMID- 29466837
TI  - Mutations in SCN3A cause early infantile epileptic encephalopathy.
AB  - OBJECTIVE: Voltage-gated sodium (Na+ ) channels underlie action potential
      generation and propagation and hence are central to the regulation of
      excitability in the nervous system. Mutations in the genes SCN1A, SCN2A, and
      SCN8A, encoding the Na+ channel pore-forming (alpha) subunits Nav1.1, 1.2, and
      1.6, respectively, and SCN1B, encoding the accessory subunit beta1 , are
      established causes of genetic epilepsies. SCN3A, encoding Nav1.3, is known to be
      highly expressed in brain, but has not previously been linked to early infantile
      epileptic encephalopathy. Here, we describe a cohort of 4 patients with epileptic
      encephalopathy and heterozygous de novo missense variants in SCN3A (p.Ile875Thr
      in 2 cases, p.Pro1333Leu, and p.Val1769Ala). METHODS: All patients presented with
      treatment-resistant epilepsy in the first year of life, severe to profound
      intellectual disability, and in 2 cases (both with the variant p.Ile875Thr),
      diffuse polymicrogyria. RESULTS: Electrophysiological recordings of mutant
      channels revealed prominent gain of channel function, with a markedly increased
      amplitude of the slowly inactivating current component, and for 2 of 3 mutants
      (p.Ile875Thr and p.Pro1333Leu), a leftward shift in the voltage dependence of
      activation to more hyperpolarized potentials. Gain of function was not observed
      for Nav1.3 variants known or presumed to be inherited (p.Arg1642Cys and
      p.Lys1799Gln). The antiseizure medications phenytoin and lacosamide selectively
      blocked slowly inactivating over transient current in wild-type and mutant Nav1.3
      channels. INTERPRETATION: These findings establish SCN3A as a new gene for
      infantile epileptic encephalopathy and suggest a potential pharmacologic
      intervention. These findings also reinforce the role of Nav1.3 as an important
      regulator of neuronal excitability in the developing brain, while providing
      additional insight into mechanisms of slow inactivation of Nav1.3. Ann Neurol
      2018;83:703-717.

PMID- 29466840
TI  - Latitudinal patterns of herbivore pressure in a temperate herb support the biotic
      interactions hypothesis.
AB  - The longstanding biotic interactions hypothesis predicts that herbivore pressure
      declines with latitude, but the evidence is mixed. To address gaps in previous
      studies, we measured herbivory and defence in the same system, quantified defence
      with bioassays, and considered effects of leaf age. We quantified herbivory and
      defence of young and mature leaves along a continental gradient in eastern North
      America in the native herb Phytolacca americana L. Herbivory in the field
      declined with latitude and was strongly correlated with lepidopteran abundance.
      Laboratory bioassays revealed that leaf palatability was positively correlated
      with latitude of origin. Young leaves were more damaged than mature leaves at
      lower latitudes in the field, but less palatable in bioassays. Both defence and
      palatability displayed non-linear latitudinal patterns, suggesting potential
      mechanisms based on biological or climatic thresholds. In sum, observational and
      experimental studies find patterns consistent with high herbivore pressure and
      stronger plant defences at lower latitudes.

PMID- 29466839
TI  - Memory complaints, dementia, and neuropathology in older blacks and whites.
AB  - OBJECTIVE: To determine relationships of memory complaints to cognitive function
      and decline, incident dementia, and neurodegenerative and other neuropathologies,
      as well as the population-attributable risk for dementia in older black and white
      persons. METHODS: A total of 4,015 community-based persons (28% black; 74% women;
      mean baseline age = 78 years) were enrolled in 1 of 4 longitudinal cohort
      studies, and another 2,937 in a population-based cohort. Memory scores, assessed
      using 2 questions (5-point Likert scales) were categorized as complaints present
      or absent. Global cognition and 5 cognitive domains were derived from annual
      neuropsychological tests. Dementia was assessed from these tests and additional
      data. Neuropathologic data were available for 1,350 deceased subjects with brain
      autopsies. Regression and mixed effects models were used to examine relationships
      of memory complaints to cognition and neuropathology. RESULTS: Baseline memory
      complaints (n = 1,310; 33% of 4,015) were associated with lower cognition and
      faster decline in all domains (global score estimate = -0.032, standard error =
      0.004, p < 0.0001), during a mean follow-up of 6 (standard deviation = 2) years.
      Persons with memory complaints had higher dementia risk (hazard ratio = 1.64, 95%
      confidence interval [CI] = 1.42-1.89) and odds of pathologic Alzheimer disease
      (odds ratio [OR] = 1.96, 95% CI = 1.51-2.54), neocortical Lewy bodies (OR = 2.47,
      95% CI = 1.54-3.96), and other neurodegenerative pathologies. Results for
      dementia risk were similar among blacks and whites. Among 2,937 older persons in
      a population-based cohort with similar data, the population-attributable risk for
      incident dementia due to memory complaints was 14.0% (95% CI = 2.6-23.0), and did
      not vary between the black and white groups. INTERPRETATION: Memory complaints
      are common in older black and white persons, and relate to cognitive decline,
      dementia risk, and neurodegenerative pathologies. Ann Neurol 2018;83:718-729.

PMID- 29466842
TI  - Introducing Ronald J. Sokol, M.D.-our 2018 AASLD president.

PMID- 29466841
TI  - Seizures and disturbed brain potassium dynamics in the leukodystrophy
      megalencephalic leukoencephalopathy with subcortical cysts.
AB  - OBJECTIVE: Loss of function of the astrocyte-specific protein MLC1 leads to the
      childhood-onset leukodystrophy "megalencephalic leukoencephalopathy with
      subcortical cysts" (MLC). Studies on isolated cells show a role for MLC1 in
      astrocyte volume regulation and suggest that disturbed brain ion and water
      homeostasis is central to the disease. Excitability of neuronal networks is
      particularly sensitive to ion and water homeostasis. In line with this, reports
      of seizures and epilepsy in MLC patients exist. However, systematic assessment
      and mechanistic understanding of seizures in MLC are lacking. METHODS: We
      analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used
      two distinct genetic mouse models of MLC to further study epileptiform activity
      and seizure threshold through wireless extracellular field potential recordings.
      Whole-cell patch-clamp recordings and K+ -sensitive electrode recordings in mouse
      brain slices were used to explore the underlying mechanisms of epilepsy in MLC.
      RESULTS: An early onset of seizures is common in MLC. Similarly, in MLC mice, we
      uncovered spontaneous epileptiform brain activity and a lowered threshold for
      induced seizures. At the cellular level, we found that although passive and
      active properties of individual pyramidal neurons are unchanged, extracellular K+
      dynamics and neuronal network activity are abnormal in MLC mice. INTERPRETATION:
      Disturbed astrocyte regulation of ion and water homeostasis in MLC causes
      hyperexcitability of neuronal networks and seizures. These findings suggest a
      role for defective astrocyte volume regulation in epilepsy. Ann Neurol
      2018;83:636-649.

PMID- 29466843
TI  - Novel short curved sphincterotome for wire-guided cannulation and endoscopic
      sphincterotomy.

PMID- 29466844
TI  - An Unusual Case of Ovarian Carcinomatosis with Microscopic Tumor Embolism Leading
      to Rectal Ischemia and Perforation.
AB  - We present an unusual case of advanced ovarian carcinoma with postoperative
      complications of ischemia and perforation of the rectum as a result of tumor
      embolism. The interval progression from ischemia to infarction of the rectum was
      captured in repeated sigmoidoscopies. A brief discussion on tumor embolism and
      management of this case is also included.

PMID- 29466845
TI  - Duodenal Niemann-Pick C1-like 1 expression was negatively correlated with liver X
      receptor expression in nonalcoholic fatty liver disease.
AB  - Background/Aims: Intestinal cholesterol absorption includes intestinal Niemann
      Pick C1-like 1 (NPC1L1) and is an important target pathway in nonalcoholic fatty
      liver disease (NAFLD). We investigated the expression of NPC1L1 and its
      correlation with liver X receptor (LXR) expression in peripheral mononuclear
      (PMN) cells in patients with NAFLD. Methods: We evaluated intestinal expression
      of NPC1L1 in 25 NAFLD patients and 28 healthy controls. We calculated the mRNA
      expression levels of LXR and farnesoid X receptor (FXR), which are master players
      of cholesterol metabolism in PMN cells. The protein expression of ABCA1, ABCG5/8,
      NPC1L1, SREBP, LXR, FXR, and CD36 was measured on tissue samples from the
      duodenum and ileum. Results: The expression of LXR (p = 0.01) and FXR (p = 0.03)
      in PMN cells was increased in the NAFLD group compared to the control group.
      Duodenal NPC1L1 decreased in the NAFLD group compared to the healthy controls
      (3.38 +/- 1.4 vs. 2.42 +/- 1.2, p = 0.05). NPC1L1 expression in the duodenum was
      negatively correlated with LXR expression in PMN cells. Expression of LXR and FXR
      in the ileum was also negatively correlated with the expression of LXR in PMN
      cells. Conclusions: Duodenal NPC1L1 expression was decreased in NAFLD and was
      negatively correlated with LXR expression in PMN cells.

PMID- 29466846
TI  - Utility of shear wave elastography to detect papillary thyroid carcinoma in
      thyroid nodules: efficacy of the standard deviation elasticity.
AB  - Background/Aims: The aim of this study was to address the role of the elasticity
      index as a possible predictive marker for detecting papillary thyroid carcinoma
      (PTC) and quantitatively assess shear wave elastography (SWE) as a tool for
      differentiating PTC from benign thyroid nodules. Methods: One hundred and
      nineteen patients with thyroid nodules undergoing SWE before ultrasound-guided
      fine needle aspiration and core needle biopsy were analyzed. The mean (EMean),
      minimum (EMin), maximum (EMax), and standard deviation (ESD) of SWE elasticity
      indices were measured. Results: Among 105 nodules, 14 were PTC and 91 were
      benign. The EMean, EMin, and EMax values were significantly higher in PTCs than
      benign nodules (EMean 37.4 in PTC vs. 23.7 in benign nodules, p = 0.005; EMin
      27.9 vs. 17.8, p = 0.034; EMax 46.7 vs. 31.5, p < 0.001). The EMean, EMin, and
      EMax were significantly associated with PTC with diagnostic odds ratios varying
      from 6.74 to 9.91, high specificities (86.4%, 86.4%, and 88.1%, respectively),
      and positive likelihood ratios (4.21, 3.69, and 4.82, respectively). The ESD
      values were significantly higher in PTC than in benign nodules (6.3 vs. 2.6, p <
      0.001). ESD had the highest specificity (96.6%) when applied with a cut-off value
      of 6.5 kPa. It had a positive likelihood ratio of 14.75 and a diagnostic odds
      ratio of 28.50. Conclusions: The shear elasticity index of ESD, with higher
      likelihood ratios for PTC, will probably identify nodules that have a high
      potential for malignancy. It may help to identify and select malignant nodules,
      while reducing unnecessary fine needle aspiration and core needle biopsies of
      benign nodules.

PMID- 29466847
TI  - Costs and clinical outcomes of patients with diffuse large B-cell lymphoma in
      first remission: role of PET/CT surveillance.
AB  - Background/Aims: The role of [18F]-f luorodeoxyglucose positron emission
      tomography-computed tomography (PET/CT) in patients with diffuse large B-cell
      lymphoma (DLBCL) in first remission is unclear. Methods: Medical costs within the
      first 3 years of treatment completion and clinical outcomes of 118 patients with
      DLBCL in first remission with and without surveillance PET/CT (PET/CT [+] group
      [n = 76] and PET/CT [-] group [n = 42], respectively) were retrospectively
      analyzed. Results: In a propensity matched cohort with adjustment for
      International Prognostic Index risk and relapse, the PET/CT (+) group was shown
      to have similar medical costs as the PET/CT (-) group. Relapse-free survival
      (RFS) and overall survival (OS) were comparable between the two groups (median
      RFS not reached [NR] for both groups, p = 0.133; median OS NR, p = 0.542). Among
      76 patients with surveillance PET/CT, 31 (40.8%) had findings suggestive of
      recurrence and 16 of these (51.6%) were later confirmed to have recurrent
      disease. Fifteen patients (48.4%) were confirmed to not have recurrence after
      follow-up CT or PET/CT evaluation (n = 10) and biopsy (n = 4). None of the
      patients with negative PET/CT findings had disease recurrence. Sensitivity,
      specificity, positive predictive value, and negative predictive value of PET/CT
      for detection of recurrence were 1, 0.75, 0.52, and 1, respectively. Conclusions:
      Surveillance PET/CT resulted in similar clinical outcomes and medical costs
      compared to no surveillance PET/CT. Approximately half of patients with PET/CT
      findings of recurrence had no recurrence after follow-up imaging and biopsy,
      which would not have been carried out if PET/CT had not been performed in the
      first place.

PMID- 29466848
TI  - Factors associated with treatment interruption in elderly patients with cancer.
AB  - Background/Aims: This study was conducted to identify risk factors that predict
      vulnerability to cancer therapy on the basis of the clinical, geriatric, and
      quality of life assessment before starting treatment in elderly patients.
      Methods: Seventy-five patients aged 65 years and over with newly diagnosed stage
      IV solid cancer receiving chemotherapy were analyzed. Clinical and laboratory
      data were collected. The geriatric assessment was performed using the Korean
      versions of the Modified Barthel Index, Instrumental Activities of Daily Living,
      Mini-Mental State Examination, and Geriatric Depression Scale. The European
      Organisation for Research and Treatment of Cancer Quality-of-Life Core
      Questionnaire (EORTC-QLQ-C30) was also performed. Results: Forty-one patients
      stopped cancer treatment during or after the end of first-line therapy and were
      classified as the treatment interruption group. By univariate analysis, treatment
      interruption was associated with metastases to >= 2 distant sites, lower albumin
      level, lower EORTC-QLQ-C30 physical and role functioning scores, and higher EORTC
      QLQ-C30 fatigue and appetite loss symptom scores. By multivariate analysis,
      treatment interruption was significantly associated with low score for the EORTC
      QLQ-C30 physical functioning scale (odds ratio [OR], 1.020; 95% confidence
      interval [CI], 1.002 to 1.039; p = 0.030), and >= 2 sites of distant metastases
      (OR, 2.965; 95% CI, 1.012 to 8.681; p = 0.047). Conclusions: The EORTC-QLQ-C30
      physical functioning score and metastases to >= 2 organs, which indicate a poor
      physical functional status and metastatic high tumor burden, were significantly
      associated with interruption of first-line treatment in elderly patients with
      cancer.

PMID- 29466849
TI  - Predictors of postoperative infectious complications in liver transplant
      recipients: experience of 185 consecutive cases.
AB  - Background/Aims: Infections following liver transplant (LT) remain a major cause
      of mortality. This study was conducted to evaluate risk factors for infection and
      to review clinical characteristics. METHODS: Medical records of patients who
      underwent LT from 2010 to 2014 were retrospectively analyzed. Binary logistic
      regression analysis was used to investigate risk factors of infection. Kaplan
      Meier analysis was used to predict prognosis of infected and non-infected groups.
      RESULTS: Of 185 recipients, 89 patients experienced infectious complications. The
      median follow-up period was 911 days (range, 9 to 2,031). The infected group had
      higher 1-year mortality (n = 22 [24.7%] vs. n = 8, [8.3%], p = 0.002), and longer
      postoperative admission days (mean: 53.7 +/- 35.8 days vs. 28.3 +/- 13.0 days, p
      < 0.001), compared to the non-infected group. High preoperative Model for End
      Stage Liver Disease (MELD) score (odds ratio [OR], 1.057; 95% confidence interval
      [CI], 1.010 to 1.105; p = 0.016), deceased-donor type (OR, 5.475; 95% CI, 2.442
      to 12.279; p < 0.001), and acute rejection (OR, 3.042; 95% CI, 1.241 to 7.454; p
      = 0.015) were independent risk factors associated with infection. Intra-abdominal
      infection (n = 35, 20.8%) was the major infectious complication. Among identified
      bacteria, Enterococcus species (28.4%) were major pathogens, followed by
      Escherichia coli and Klebsiella species. Conclusions: High preoperative MELD
      score, deceased-donor type, and acute rejection were risk factors associated with
      infection. To prevent infections following surgery, it is important to determine
      the appropriate time of operation before the recipient has a high MELD score.

PMID- 29466850
TI  - Direct costs of severe cutaneous adverse reactions in a tertiary hospital in
      Korea.
AB  - Background/Aims: There are only a few reports on the direct costs of severe
      cutaneous adverse reactions (SCARs), including drug reaction with eosinophilia
      and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic
      epidermal necrolysis (TEN), despite the tremendous negative impact these
      reactions can have on patients. We estimated the direct costs of treating SCARs.
      Methods: Patients admitted to a tertiary teaching hospital for the treatment of
      SCARs from January 1, 2005 to December 31, 2010 were included. Patients who had
      experienced SCARs during their admission for other medical conditions were
      excluded. The direct costs of hospitalization and outpatient department visits
      were collected. Inpatient and outpatient care costs were calculated, and factors
      affecting inpatient care costs were analyzed. Results: The total healthcare cost
      for the management of 73 SCAR patients (36 with DRESS, 21 with SJS, and 16 with
      TEN) was 752,067 US dollars (USD). Most of the costs were spent on inpatient care
      (703,832 USD). The median inpatient care cost per person was 3,720 (range, 1,133
      to 107,490) USD for DRESS, 4,457 (range, 1,224 to 21,428) USD for SJS, and 8,061
      (range, 1,127 to 52,220) USD for TEN. Longer hospitalization significantly
      increased the inpatient care costs of the patients with DRESS (by 428 USD [range,
      395 to 461] per day). Longer hospitalization and death significantly increased
      the inpatient care costs of the patients with SJS/TEN (179 USD [range, 148 to
      210] per day and an additional 14,425 USD [range, 9,513 to 19,337] for the
      deceased). Conclusions: The management of SCARs required considerable direct
      medical costs. SCARs are not only a health problem but also a significant
      financial burden for the affected individuals.

PMID- 29466851
TI  - Seropositive rate of the anti-hepatitis A immunoglobulin G antibody in
      maintenance hemodialysis subjects from two hospitals in Korea.
AB  - Background/Aims: Hepatitis A virus (HAV) is a self-limiting infectious disease,
      but 1% of subjects develop fulminant hepatitis. The prevalence of the anti-HAV
      immunoglobulin G (IgG) antibody in hemodialysis subjects in Korea remains
      unknown. The purpose of this study was to describe and compare the seropositive
      rate of anti-HAV antibody among hemodialysis subjects in two hospitals according
      to age group. Methods: A total of 170 hemodialysis subjects were evaluated for
      the seropositive rate of the anti-HAV IgG antibody and its titer. Results: Of the
      170 maintenance hemodialysis subjects in two hospitals (Kangnam 92 vs. Chuncheon
      78), 79 (46.5%) were male. The mean age was 53.2 years old, and 94.1% of the
      subjects were over 40 years old. The median vintage of hemodialysis was 29.0
      months. Anti-HAV antibody was found in 163 subjects (95.9%), with no significant
      difference between the two areas (Kangnam 97.8% [n = 90] vs. Chuncheon 93.6% [n =
      73]). Subjects younger than 40 years old showed a seropositive rate of 50%, while
      the seropositive rate increased with age for subjects aged 40 or older (p for
      trend < 0.001). Seropositive subjects from Kangnam showed a higher anti-HAV
      antibody titer than those from Chuncheon (median: Kangnam 14.2 vs. Chuncheon
      11.7). Only age influenced seropositivity. The only factor that influenced the
      antibody level was the location of hospital (p < 0.001). Conclusions: The
      seropositive rate of the anti-HAV antibody in hemodialysis subjects was 95%,
      which is similar to findings in the general population. Active immunization
      against hepatitis A is strongly recommended for hemodialysis subjects under 40
      years of age after anti-HAV testing.

PMID- 29466852
TI  - Primary large cell neuroendocrine carcinoma of the common hepatic duct mimicking
      a Klatskin tumor.

PMID- 29466853
TI  - Synthesis and Evaluation of a Novel 64Cu- and 67Ga-Labeled Neurokinin 1 Receptor
      Antagonist for in Vivo Targeting of NK1R-Positive Tumor Xenografts.
AB  - Neurokinin 1 receptor (NK1R) is expressed in gliomas and neuroendocrine
      malignancies and represents a promising target for molecular imaging and targeted
      radionuclide therapy. The goal of this study was to synthesize and evaluate a
      novel NK1R ligand (NK1R-NOTA) for targeting NK1R-expressing tumors. Using a
      carboxymethyl moiety linked to L-733060 as a starting reagent, NK1R-NOTA was
      synthesized in a three-step reaction and then labeled with 64Cu (or 67Ga for in
      vitro studies) in the presence of CH3COONH4 buffer. The radioligand affinity and
      cellular uptake were evaluated with NK1R-transduced HEK293 cells (HEK293-NK1R)
      and NK1R nontransduced HEK293 cells (HEK293-WT) and their xenografts.
      Radiolabeled NK1R-NOTA was obtained with a radiochemical purity of >95% and
      specific activities of >7.0 GBq/MUmol for 64Cu and >5.0 GBq/MUmol for 67Ga. Both
      64Cu- and 67Ga-labeled NK1R-NOTA demonstrated high levels of uptake in HEK293
      NK1R cells, whereas co-incubation with an excess of NK1R ligand L-733060 reduced
      the level of uptake by 90%. Positron emission tomography (PET) imaging showed
      that [64Cu]NK1R-NOTA had a accumulated rapidly in HEK293-NK1R xenografts and a 10
      fold lower level of uptake in HEK293-WT xenografts. Radioactivity was cleared by
      gastrointestinal tract and urinary systems. Biodistribution studies confirmed
      that the tumor-to-organ ratios were >=5 for all studied organs at 1 h p.i.,
      except kidneys, liver, and intestine, and that the tumor-to-intestine and tumor
      to-kidney ratios were also improved 4 and 20 h post-injection. [64Cu]NK1R-NOTA is
      a promising ligand for PET imaging of NK1R-expressing tumor xenografts. Delayed
      imaging with [64Cu]NK1R-NOTA improves image contrast because of the continuous
      clearance of radioactivity from normal organs.

PMID- 29466854
TI  - Long Spin-Relaxation Times in a Transition-Metal Atom in Direct Contact to a
      Metal Substrate.
AB  - Long spin-relaxation times are a prerequisite for the use of spins in data
      storage or nanospintronics technologies. An atomic-scale solid-state realization
      of such a system is the spin of a transition-metal atom adsorbed on a suitable
      substrate. For the case of a metallic substrate, which enables the direct
      addressing of the spin by conduction electrons, the experimentally measured
      lifetimes reported to date are on the order of only hundreds of femtoseconds.
      Here, we show that the spin states of iron atoms adsorbed directly on a
      conductive platinum substrate have a surprisingly long spin-relaxation time in
      the nanosecond regime, which is comparable to that of a transition metal atom
      decoupled from the substrate electrons by a thin decoupling layer. The
      combination of long spin-relaxation times and strong coupling to conduction
      electrons implies the possibility to use flexible coupling schemes to process the
      spin information.

PMID- 29466855
TI  - Nano-Assembly of Pamitoyl-Bioconjugated Coenzyme-A for Combinatorial Chemo
      Biologics in Transcriptional Therapy.
AB  - Pathogenesis, the biological mechanism that leads to the diseased state, of many
      cancers is driven by interruptions to the role of Myc oncoprotein, a regulator
      protein that codes for a transcription factor. One of the most significant
      biological interruptions to Myc protein is noted as its dimerization with Max
      protein, another important factor of family of transcription factors. Binding of
      this heterodimer to E-Boxes, enhancer boxes as DNA response element found in some
      eukaryotes that act as a protein-binding site and have been found to regulate
      gene expression, are interrupted to regulate cancer pathogenesis. The systemic
      effectiveness of potent small molecule inhibitors of Myc-Max dimerization has
      been limited by poor bioavailability, rapid metabolism, and inadequate target
      site penetration. The potential of gene therapy for targeting Myc can be fully
      realized by successful synthesis of a smart cargo. We developed a "nuclein" type
      nanoparticle "siNozyme" (45 +/- 5 nm) from nanoassembly of pamitoyl-bioconjugated
      acetyl coenzyme-A for stable incorporation of chemotherapeutics and biologics to
      achieve remarkable growth inhibition of human melanoma. Results indicated that
      targeting transcriptional gene cMyc with siRNA with codelivery of a topoisomerase
      inhibitor, amonafide caused ~90% growth inhibition and 95% protein inhibition.

PMID- 29466856
TI  - Enhanced Cellular Ablation by Attenuating Hypoxia Status and Reprogramming Tumor
      Associated Macrophages via NIR Light-Responsive Upconversion Nanocrystals.
AB  - Near-infrared (NIR) light-mediated photodynamic therapy (PDT), especially based
      on lanthanide-doped upconversion nanocrystals (UCNs), have been extensively
      investigated as a promising strategy for effective cellular ablation owing to
      their unique optical properties to convert NIR light excitation into multiple
      short-wavelength emissions. Despite the deep tissue penetration of NIR light in
      living systems, the therapeutic efficiency is greatly restricted by insufficient
      oxygen supply in hypoxic tumor microenvironment. Moreover, the coexistent tumor
      associated macrophages (TAMs) play critical roles in tumor recurrence during the
      post-PDT period. Herein, we developed a unique photosensitizer-loaded UCNs
      nanoconjugate (PUN) by integrating manganese dioxide (MnO2) nanosheets and
      hyaluronic acid (HA) biopolymer to improve NIR light-mediated PDT efficacy
      through attenuating hypoxia status and synergistically reprogramming TAMs
      populations. After the reaction with overproduced H2O2 in acidic tumor
      microenvironment, the MnO2 nanosheets were degraded for the production of massive
      oxygen to greatly enhance the oxygen-dependent PDT efficiency upon 808 nm NIR
      light irradiation. More importantly, the bioinspired polymer HA could effectively
      reprogram the polarization of pro-tumor M2-type TAMs to anti-tumor M1-type
      macrophages to prevent tumor relapse after PDT treatment. Such promising results
      provided the great opportunities to achieve enhanced cellular ablation upon NIR
      light-mediated PDT treatment by attenuating hypoxic tumor microenvironment, and
      thus facilitated the rational design of new generations of nanoplatforms toward
      immunotherapy to inhibit tumor recurrence during post-PDT period.

PMID- 29466857
TI  - Sensitive and Selective Fluorescent Probe for Selenol in Living Cells Designed
      via a p Ka Shift Strategy.
AB  - Selenocysteine (Sec) is a primary kind of reactive selenium species in cells, and
      its vital roles in physiological processes have been featured. Thus, the
      development of highly sensitive and selective methods for the sensing of Sec is
      of great significance. This work reports a turn-on fluorescent probe for selenol
      based on the unique fluorescence OFF-ON switching between the Schiff base (SB)
      and its complementary protonated Schiff base (PSB) form of merocyanine dyes. The
      probe consists of a merocyanine Schiff base fluorophore and a 2,4
      dinitrobenzenesulfonamide moiety that reacts especially with selenol. The
      fluorescence turn-on response of MC-Sec is realized via the selective removal of
      the strongly electron withdrawing 2,4-dinitrobenzenesulfonyl group by Sec,
      leading to a shift in the p Ka of the imine nitrogen of the probe from 6.40 to
      9.04 and thus significantly increasing the population of the fluorescent PSB form
      of the dye at physiological pH. MC-Sec shows good selectivity and sensitivity for
      Sec and has been applied in the imaging of exogenous and endogenous selenol in
      living cells by confocal fluorescence microscopy. The proposed mechanism should
      be useful for developing future probes directed to other target molecules by
      employing this simple but effective p Ka shift strategy.

PMID- 29466858
TI  - Release of Terminal Alkynes via Tandem Photodeprotection and Decarboxylation of o
      Nitrobenzyl Arylpropiolates in a Flow Microchannel Reactor.
AB  - Photocleavable protecting groups (PPGs) offer a complementary protection paradigm
      compared to traditional protection groups. Herein, an o-nitrobenzyl (NB) PPG was
      employed to protect a variety of arylpropiolic acids. Upon a cascade of light
      triggered photodeprotection in a microchannel reactor (residence times of 100-500
      s), followed by Cu-catalyzed decarboxylation at 60  degrees C, the NB-protected
      arylpropiolic acid afforded a terminal alkyne. This terminal alkyne was further
      reacted in situ with an azide via click chemistry to yield a 1,2,3-triazole in a
      one-pot reaction. Furthermore, the effect of different substituents (methyl,
      vinyl, allyl, and phenyl) at the benzylic position on the rate of
      photodeprotection was studied. The quantum yields of photolysis for the benzylic
      substituted esters were determined to be as high as 0.45 compared to the
      unsubstituted ester with a 0.08 quantum yield of photolysis.

PMID- 29466859
TI  - Transferable Coarse-Grained Models of Liquid-Liquid Equilibrium Using Local
      Density Potentials Optimized with the Relative Entropy.
AB  - Bottom-up coarse-grained (CG) models are now regularly pursued to enable large
      length and time scale molecular simulations of complex, often macromolecular
      systems. However, predicting fluid phase equilibria using such models remains
      fundamentally challenging. A major problem stems from the typically low
      transferability of CG models beyond the densities and/or compositions at which
      they are parametrized, which is necessary if they are to describe distinct
      structural and thermodynamic properties unique to each phase. CG model
      transferability is compounded by the representation of the inherently multibody
      coarse interactions using pair potentials that neglect higher order effects.
      Here, we propose to construct transferable single site CG models of liquid
      mixtures by supplementing traditional CG pair interactions with local density
      potentials, which constitute a computationally inexpensive mean-field approach to
      describe many-body effects, in that site energies are modulated by the local
      solution environment. To illustrate the approach, we use intra- and interspecies
      local density potentials to develop CG models of benzene-water solutions that
      show impressive transferability in structural metrics (pair correlation
      functions, density profiles) throughout composition space, in contrast to pair
      only CG representations. While further refinement may be necessary to represent
      more complex thermodynamic properties, like the liquid-liquid interfacial
      tension, the generality and improvement offered by the local density approach are
      highly encouraging for enabling complex phase equilibrium modeling using CG
      models.

PMID- 29466860
TI  - Simulations of Pure Ceramide and Ternary Lipid Mixtures as Simple Interior
      Stratum Corneum Models.
AB  - The barrier function of the stratum corneum (SC) is intimately related to the
      structure of the lipid matrix, which is composed of ceramides (Cer), cholesterol
      (Chol), and free fatty acid (FFA). In this study, the all-atom CHARMM36 (C36)
      force field is used to simulate bilayers of N-palmitoylsphingosine (Cer16), N
      lignoceroylsphingosine (Cer24), Chol, and lignoceric acid (LA) as simple models
      of the SC. Equimolar mixtures of Cer, Chol, and LA are replicated from experiment
      for comparison and validation of the C36 force field, and the effects of lipid
      diversity and temperature are studied. The presence of Chol and LA have effects
      on nearly all membrane properties including surface area per lipid, area
      compressibility moduli, chain order, Chol tilt, bilayer thickness,
      interdigitation, hydrogen bonding, and lipid clustering, while temperature has a
      more moderate effect. In systems containing Cer16, there is a profound difference
      in interdigitation between pure Cer and mixed systems, while systems containing
      Cer24 are relatively unaffected. Increasing temperature has the potential to
      shift hydrogen bonding pairs rather than uniformly decrease bonding, which can
      lead to greater Cer-Cer bonding at higher temperatures. Comparison with deuterium
      order parameter experiments demonstrates good agreement, which supports further
      use of this class of lipids and fatty acids for development of more complex SC
      models.

PMID- 29466862
TI  - CD4+ T Cell Recovery and Hepatitis B Virus Coinfection in HIV-Infected Patients
      from Cote d'Ivoire Initiating Antiretroviral Therapy.
AB  - Immunorecovery could be attenuated in HIV-hepatitis B virus (HBV) coinfection
      versus HIV monoinfection during antiretroviral therapy (ART), yet, whether it
      also occurs in individuals from sub-Saharan Africa without severe comorbidities
      is unknown. In this study, 808 HIV-infected patients in Cote d'Ivoire initiating
      continuous ART were included. Six-month CD4+ count trajectories and the
      proportion reaching CD4+ T cell counts >350/mm3, HIV-RNA <300 copies/mL, still
      alive and not lost to follow-up within 18 months ("optimal immunorecovery") were
      compared between coinfected groups. At inclusion, 80 (9.9%) patients were HIV-HBV
      coinfected, 40 (50.0%) of whom had high HBV-DNA viral load (VL) (>104 copies/mL).
      Coinfected patients with high HBV-DNA replication initiated ART with
      significantly lower median CD4+ T cell counts [216/mm3, interquartile range (IQR)
      = 150-286] compared to coinfection with low HBV-DNA replication (268/mm3, IQR =
      178-375) or HIV monoinfection (257/mm3, IQR = 194-329) (p = .003). These patients
      had significantly faster rates of CD4+ cell count increase from baseline after
      adjusting for baseline age, World Health Organization stage III/IV, and CD4+ cell
      counts (p = .04), yet, were not more likely to exhibit optimal immunorecovery
      (82.5% vs. 80.0% and 77.9%, respectively) (p = .8). In conclusion, change in CD4+
      cell counts after ART-initiation was accelerated in coinfected patients with high
      HBV DNA VLs, but this did not lead to increased rates of optimal immunorecovery.

PMID- 29466861
TI  - Flexibility-Not just for yoga anymore!
AB  - Over the past few years, nucleosides have maintained a prominent role as one of
      the cornerstones of antiviral and anticancer therapeutics, and many approaches to
      nucleoside drug design have been pursued. One such approach involves flexibility
      in the sugar moiety of nucleosides, for example, in the highly successful anti
      HIV and HBV drug tenofovir. In contrast, introduction of flexibility to the
      nucleobase scaffold has only more recently gained significance with the invention
      of our fleximers. The history, development, and some biological relevance for
      this innovative class of nucleosides are detailed herein.

PMID- 29466863
TI  - OBSERVE-5: Comparison of Etanercept-Treated Psoriasis Patients From Canada and
      the United States.
AB  - BACKGROUND: OBSERVE-5 surveillance registry results evaluating etanercept safety
      and effectiveness in patients with moderate to severe psoriasis from Canada and
      the United States have been reported from data collected between May 2006 and
      December 2012. Although both countries have an identical indicated starting dose,
      the maintenance dose can differ and thus affect management strategies and
      outcomes. OBJECTIVE: To compare the long-term safety and effectiveness outcomes
      of etanercept in the Canadian and US cohorts. METHODS: Primary end points
      included exposure-adjusted event incidence rates of serious adverse events and
      serious infectious events. Secondary end points included exposure-adjusted event
      incidence rates of events of medical interest and efficacy outcomes. RESULTS:
      Over 5 years, Canadian patients received a higher maintenance dose of etanercept
      (50 mg twice/week) more frequently than those from the United States. Safety
      outcome comparisons revealed that Canadian patients had a significantly lower
      occurrence of serious adverse events than patients from the United States, with
      an overall exposure-adjusted event incidence rate per 100 patient-years of 4.46
      (95% confidence interval [CI], 3.05-6.29) vs 7.76 (95% CI 7.04-8.54),
      respectively. Serious infectious event rates were not significantly different
      between the 2 countries. Secondary outcomes of events of medical interest and
      effectiveness also did not reveal significant differences between the 2 cohorts.
      CONCLUSION: After 5 years of etanercept use, safety and effectiveness outcomes
      were similar between patients from Canada and the United States, with the
      exception of a significantly lower rate of serious adverse events in the Canadian
      population.

PMID- 29466864
TI  - Quality of Life in a Hospice: A Validation of the Croatian Version of the EORTC
      QLQ-C15-PAL.
AB  - PURPOSE: Quality of life is the cornerstone of palliative care, and assessing it
      requires validated and standardized questionnaires. However, the majority of
      questionnaires are not tested in a hospice setting. The purpose of this study is
      to evaluate the quality of life in a hospice using the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for
      Palliative Care (PAL) (EORTC QLQ-C15-PAL) questionnaire and validating it in
      Croatian language. METHODS: The study was conducted prospectively on 151
      consecutive patients who were evaluated at the admittance to the hospice and
      after 7 days. Along with the EORTC QLQ-C15-PAL, both evaluations included the
      Edmonton Symptom Assessment System (ESAS) and the Palliative Performance Score
      (PPS) version 2. Cronbach alpha coefficient was used to test the reliability of
      multi-item scales, while construct and concurrent validity was tested using the
      Pearson correlation coefficients. Known-group validity was evaluated using the
      Student t test. RESULTS: Physical functioning, pain, and emotional functioning
      scales all exhibited high reliability on both assessments and met the criteria of
      Cronbach alpha >=.70, while fatigue scale met the predetermined criteria in the
      follow-up assessment (alpha = .90). Adequate validity was also displayed, with
      the highest correlation coefficients between the EORTC QLQ-C15-PAL and ESAS
      scales recorded for the corresponding items. The EORTC QLQ-C15-PAL was also able
      to distinguish patients with different PPS scores, exhibiting excellent clinical
      validity. CONCLUSIONS: The EORTC QLQ-C15-PAL can be used successfully in Croatian
      palliative care. However, inevitable issues such as low retest percentage due to
      short survival and low physical functioning scores need to be acknowledged in
      further formulations of quality of life questionnaires specific to hospice care.

PMID- 29466865
TI  - Regulation of NADPH Oxidases by G Protein-Coupled Receptors.
AB  - SIGNIFICANCE: G protein-coupled receptors (GPCR) are the largest group of cell
      surface receptors, which link cells to their environment. Reactive oxygen species
      (ROS) can act as important cellular signaling molecules. The family of NADPH
      oxidases generates ROS in response to activated cell surface receptors. Recent
      Advances: Various signaling pathways linking GPCRs and activation of NADPH
      oxidases have been characterized. CRITICAL ISSUES: Still, a more detailed
      analysis of G proteins involved in the GPCR-mediated activation of NADPH oxidases
      is needed. In addition, a more precise discrimination of NADPH oxidase activation
      due to either upregulation of subunit expression or post-translational subunit
      modifications is needed. Also, the role of noncanonical modulators of NADPH
      oxidase activation in the response to GPCRs awaits further analyses. FUTURE
      DIRECTIONS: As GPCRs are one of the most popular classes of investigational drug
      targets, further detailing of G protein-coupled mechanisms in the activation
      mechanism of NADPH oxidases as well as better understanding of the link between
      newly identified NADPH oxidase interaction partners and GPCR signaling will
      provide new opportunities for improved efficiency and decreased off target
      effects of therapies targeting GPCRs.

PMID- 29466866
TI  - Chromosome 7q11.23 duplication syndrome presenting as neuropsychiatric regression
      in late adolescence: A new manifestation of a new syndrome?

PMID- 29466867
TI  - Response: Anorexia nervosa, more than a body image disorder.

PMID- 29466868
TI  - Finding the optimal treatment model: A systematic review of treatment for co
      occurring alcohol misuse and depression.
AB  - OBJECTIVES: Alcohol misuse and depression are commonly co-occurring conditions.
      To date, no review has examined the most efficacious treatment model for
      psychosocial treatment of co-occurring alcohol misuse and depression. This
      systematic review determined the: (i) methodological quality of publications
      examining psychosocial treatment of co-occurring alcohol misuse and depression
      using a sequential, parallel or integrated treatment model; and (ii)
      effectiveness of each dual treatment model compared to single treatment for those
      with co-occurring alcohol misuse and depression. METHODS: PubMed, Medline and
      PsycInfo databases were searched for studies which were included if they involved
      treatment for alcohol misuse and depression and could be classified into one of
      the three treatment models. Included studies were assessed using the Cochrane's
      Effective Practice and Organisation of Care risk of bias criteria. Relevant study
      characteristics and outcomes were extracted and are presented in a narrative
      review format. RESULTS: Seven studies met inclusion criteria. None were
      categorised as low risk on the risk of bias criteria. No studies examined a
      sequential model of treatment, three examined a parallel model and four examined
      an integrated model of dual-focussed treatment. The studies examining the
      parallel model and two out of four studies examining the effectiveness of an
      integrated model demonstrated greater improvement for alcohol or depression
      outcomes compared to control conditions. CONCLUSION: Evidence for the
      psychosocial treatment of co-occurring alcohol misuse and depression is limited
      to a handful of studies. The evidence has several methodological limitations,
      which impact the interpretation of the findings. Therefore, while international
      guidelines recommend integrated dual-focussed treatment for co-occurring
      conditions, there is little evidence supporting the superiority of this treatment
      format for co-occurring alcohol misuse and depression. High-quality research
      demonstrating improvements in patient outcomes is required to ensure
      recommendations for clinical practice are based on strong empirical evidence.

PMID- 29466869
TI  - Patient-specific CT-based 3D passive FSI model for left ventricle in hypertrophic
      obstructive cardiomyopathy.
AB  - Left ventricular outflow tract obstruction is observed in 70% of patients with
      hypertrophic cardiomyopathy, which occurs in about 1 of every 500 adults in the
      general population. It has been widely believed that the motion of the mitral
      valve, in particular, its systolic anterior motion (SAM), attributes
      significantly to such obstruction. For a better understanding of the mitral valve
      motion, a 3D patient-specific fluid-structure interaction model of the left
      ventricle from a patient with hypertrophic obstructive cardiomyopathy based on
      computed tomography (CT) scan images was proposed in this study. Displacement,
      structural stress, pressure, flow velocity and shear stress within the left
      ventricle and mitral valve were extracted to characterize their behavior. The
      maximum shear stress on mitral valve was 9.68 [Formula: see text]. The pressure
      on its posterior leaflet was higher than that on the anterior leaflet and the
      peak pressure on the mitral valve was 93.5 mm Hg which occurred at pre-SAM time.
      High angles of attack (54.3 +/- 22.4 degrees ) were found in this patient. The
      methodology established in this study may have the potential to clarify the
      mechanisms of SAM and ultimately optimize surgical planning by comparing the
      mechanical results obtained from preoperative and postoperative models.

PMID- 29466870
TI  - How Reliable Is the Intraoperative Assessment of Residual Fragments During
      Percutaneous Nephrolithotomy? A Prospective Study.
AB  - OBJECTIVES: To determine the accuracy of the surgeon's impression as to the stone
      free rate at the end of percutaneous nephrolithotomy (PCNL), and to evaluate
      predictors for inaccurate estimation. MATERIALS AND METHODS: A prospective study
      conducted between 2010 and 2015. Surgeon's impression, categorized as
      "insignificant residual fragments (RFs)" (<4 mm) or "significant RF" (>4 mm), was
      recorded at the end of PCNL, and was compared with postoperative imaging results,
      using CT or a combination of US and kidney, ureter, and bladder radiograph for
      radiolucent and radio-opaque stones, respectively. The association between missed
      significant RF and the patient and operative variables was evaluated with
      univariable and multivariable logistic regression analysis. RESULTS: The study
      cohort included 312 patients. Significant RFs were found in 75 (24%) patients,
      comprising all 22 patients in whom RFs were suspected (100%) and 53 patients who
      were considered stone free (18.6%). The sensitivity, specificity, and positive
      and negative predictive value of the surgeon's estimation for the absence of
      significant RFs were 100%, 39%, 0.83, and 1 for radiopaque stones, and 100%,
      12.5%, 0.75, and 1 for radiolucent stones. On multivariate analysis, multiple
      stones (OR = 4, 95% CI: 1.85-8.7, p < 0.001) and cumulative stone size (OR =
      1.04, 95% CI: 1.02-1.1, p = 0.005) were independent predictors for missed RFs.
      CONCLUSION: In approximately fifth of the patients undergoing PCNL, the surgeon's
      impression of "insignificant RF" may be inaccurate. Stone size and number were
      independently associated with higher miss rate. These data should be shared with
      the patients when the postoperative drainage method and the option for an
      auxiliary procedure are discussed.

PMID- 29466871
TI  - Design of a Novel Gene Therapy Construct to Achieve Sustained Brain-Derived
      Neurotrophic Factor Signaling in Neurons.
AB  - Brain-derived neurotrophic factor (BDNF) acting through the tropomyosin-related
      receptor-B (TrkB) is an important signaling system for the maintenance and
      survival of neurons. Gene therapy using either recombinant adeno-associated virus
      (AAV) or lentiviral vectors can provide sustained delivery of BDNF to tissues
      where reduced BDNF signaling is hypothesized to contribute to disease
      pathophysiology. However, elevation in BDNF at target sites has been shown to
      lead to a downregulation of TrkB receptors, thereby reducing the effect of
      chronic BDNF delivery over time. A novel gene sequence has been designed coding
      both the ligand (BDNF) and the TrkB receptor in a single transgene separated by a
      short viral-2A sequence. The single transgene is efficiently processed
      intracellularly in vitro and in vivo to yield the two mature proteins, which are
      then independently transported to their final cellular locations: TrkB receptors
      to the cell surface, and BDNF contained within secretory vesicles. To accommodate
      the coding sequences of both BDNF and TrkB receptors within the narrow confines
      of the AAV vectors (4.7 kb pairs), the coding region for the pro-domain of BDNF
      was removed and the signal peptide sequence modified to improve production,
      intracellular transport, and secretion of mature BDNF (mBDNF). Intracellular
      processing and efficacy was shown in HEK293 cells and SH-SY5Y neuroblastoma cells
      using plasmid DNA and after incorporating the TrkB-2A-mBDNF into an AAV2 vector.
      Increased BDNF/TrkB-mediated intracellular signaling pathways were observed after
      AAV2 vector transfection while increased TrkB phosphorylation could be detected
      in combination with neuroprotection from hydrogen peroxide-induced oxidative
      stress. Correct processing was also shown in vivo in mouse retinal ganglion cells
      after AAV2 vector administration to the eye. This novel construct is currently
      being investigated for its efficacy in animal models to determine its potential
      to progress to human clinical studies in the future.

PMID- 29466872
TI  - Attenuation of EGFL7 Expression Inhibits Growth Hormone-Producing Pituitary
      Adenomas Growth and Invasion.
AB  - Invasiveness of growth hormone-producing pituitary adenomas (GHPAs) causes
      difficulties in safe and complete adenoma removal during surgery and often leads
      to high recurrence. Epidermal growth factor-like domain 7 (EGFL7) has been shown
      to be able to promote tumor angiogenesis, growth, invasiveness, and metastasis
      through the Notch signaling pathway. It was previously demonstrated that EGFL7
      was overexpressed in GHPAs. This study reports that EGFL7 and Notch2 (positive
      correlation with EGFL7) are overexpressed in invasive GHPA. A long-rank test
      (Kaplan-Meier method) shows that invasive GHPAs with EGFL7 strong expression
      results in reduced recurrence-free survival. Multivariate Cox regression analysis
      reveals that weak EGFL7 expression is an independent prognostic factor for
      recurrence-free survival. In addition, knockdown of EGFL7 expression suppresses
      proliferation and invasion of GH3 and GT1-1 cells in vitro. Moreover, attenuation
      of EGFL7 inhibits human GHPA growth in vivo. The data suggest that as a Notch
      agonist, EGFL7 may potentially be an appropriate novel molecular target for
      future development of GHPA medical therapy.

PMID- 29466873
TI  - The relationship between Pittsburgh Sleep Quality Index subscales and diabetes
      control.
AB  - Objectives Data suggest that poor sleep quality as measured by the Pittsburgh
      Sleep Quality Index (PSQI) contributes to suboptimal diabetes control. How the
      subscales comprising the PSQI individually relate to diabetes control is poorly
      understood. Methods In order to explore how PSQI subscales relate to diabetes
      control, we analyzed baseline data from a trial of a telemedicine intervention
      for diabetes. We used multivariable modeling to examine: (1) the relationship
      between the global PSQI and hemoglobin A1c (HbA1c); (2) the relationships between
      the 7 PSQI subscales and HbA1c; and (3) medication nonadherence as a possible
      mediating factor. Results Global PSQI was not associated with HbA1c ( n = 279).
      Only one PSQI subscale, sleep disturbances, was associated with HbA1c after
      covariate adjustment; HbA1c increased by 0.4 points for each additional sleep
      disturbances subscale point (95%CI 0.1 to 0.8). Although the sleep disturbances
      subscale was associated with medication nonadherence (OR 2.04, 95%CI 1.27 to
      3.30), a mediation analysis indicated nonadherence does not mediate the sleep
      disturbances-HbA1c relationship. Discussion The sleep disturbances subscale may
      drive the previously observed relationship between PSQI and HbA1c. The mechanism
      for the relationship between sleep disturbances and HbA1c remains unclear, as
      does the impact on HbA1c of addressing sleep disturbances.

PMID- 29466874
TI  - Patient expertise: Contested territory in the realm of long-term condition care.
AB  - Objectives The aim of this study was to describe the experience of people with
      multiple long-term conditions with particular reference to the notion of the
      'expert patient' in the context of self-management. Methods A multiple case study
      of 16 people with several long-term conditions, included interviews and contacts
      over an 18-month period and an interview with their primary care clinicians.
      Analysis included both case-by-case and some cross-case analysis. Results The
      findings reveal the patient participants had little capacity to exercise the
      agency necessary be an expert patient as premised. Weariness, shame, expertise,
      issues of compliance and control and collaboration are contested areas
      underpinning clinician encounters. Discussion Patient expertise is at the heart
      of self-management approaches but the findings surfaced several inherent
      contradictions between the idealised expert patient and their position within a
      health care system that is entrenched in biomedicine. Conclusion There is a
      mismatch between how the self-management approach has been operationalised and
      what the participants who have multiple LTCs reveal as what they want and need.
      The research concludes that the self-management approach is inappropriate for
      people with multiple LTCs and that other ways of offering care should be
      considered.

PMID- 29466876
TI  - SREBP2 contributes to cisplatin resistance in ovarian cancer cells.
AB  - This study is to investigate transcription factors involved in cisplatin
      resistance in ovarian cancer cells. The transcriptome of cisplatin resistant and
      sensitive A2780 epithelial ovarian cancer cells was obtained from GSE15372.
      Ovarian transcriptome data GSE62944 was downloaded from TCGA and applied for
      transcription regulatory network analysis. The analysis results were confirmed
      using quantitative polymerase chain reaction. The roles of SREBP2 in cisplatin
      resistant cells were investigated by RNA inference and cell viability analysis.
      Transcription regulatory network analysis found that 12 transcription factors and
      their targets were involved in cisplatin resistant in A2780 cells. Among these
      factors, the targets of EZH2 and SREBP2 revealed by Transcriptional Regulatory
      Relationships Unraveled by Sentence-based Text mining were also enriched in
      differentially expressed genes between cisplatin resistant and cisplatin
      sensitive cells. Their targets were enriched mainly in cell cycle and cholesterol
      metabolic process, respectively. Bioinformatic analysis illustrated three known
      targets of SREBP2, namely LDLR, FDFT1, and HMGCR were increased in A2780
      resistant cell lines. Additionally, the three genes and SREBP2 were also elevated
      in live cells after cisplatin treatment via quantitative polymerase chain
      reaction. Importantly, RNA inference of SREBP2 in A2780 cell line resulted in a
      decrease of cell viability after cisplatin treatment. SREBP2 played important
      roles in cisplatin resistance and cholesterol metabolic process might be a novel
      target for cancer therapy. Impact statement Transcriptome of cisplatin resistant
      and sensitive A2780 epithelial ovarian cancer cells was obtained from GSE15372
      and TCGA. Twelve transcription factors and their targets were involved in
      cisplatin resistant. Among these factors, the targets of EZH2 and SREBP2 revealed
      by Transcriptional Regulatory Relationships Unraveled by Sentence-based Text
      mining were also enriched in differentially expressed genes. Their targets were
      enriched mainly in cell cycle and cholesterol metabolic process. Three targets of
      SREBP2, namely LDLR, FDFT1, and HMGCR were increased in A2780-resistant cell
      lines and were found elevated in live cells after cisplatin treatment via qPCR.
      RNAi of SREBP2 in A2780 cell line resulted in a decrease of cell viability after
      cisplatin treatment. SREBP2 played important roles in cisplatin resistance and
      might be a novel target for cancer therapy.

PMID- 29466875
TI  - Impacts of maternal dietary protein intake on fetal survival, growth, and
      development.
AB  - Maternal nutrition during gestation, especially dietary protein intake, is a key
      determinant in embryonic survival, growth, and development. Low maternal dietary
      protein intake can cause embryonic losses, intra-uterine growth restriction, and
      reduced postnatal growth due to a deficiency in specific amino acids that are
      important for cell metabolism and function. Of note, high maternal dietary
      protein intake can also result in intra-uterine growth restriction and embryonic
      death, due to amino acid excesses, as well as the toxicity of ammonia,
      homocysteine, and H2S that are generated from amino acid catabolism. Maternal
      protein nutrition has a pronounced impact on fetal programming and alters the
      expression of genes in the fetal genome. As a precursor to the synthesis of
      molecules (e.g. nitric oxide, polyamines, and creatine) with cell signaling and
      metabolic functions, L-arginine (Arg) is essential during pregnancy for growth
      and development of the conceptus. With inadequate maternal dietary protein
      intake, Arg and other important amino acids are deficient in mother and fetus.
      Dietary supplementation of Arg during gestation has been effective in improving
      embryonic survival and development of the conceptus in many species, including
      humans, pigs, sheep, mice, and rats. Both the balance among amino acids and their
      quantity are critical for healthy pregnancies and offspring. Impact statement
      This review aims at: highlighting adverse effects of elevated levels of ammonia
      in mother or fetus on embryonic/fetal survival, growth, and development; helping
      nutritionists and practitioners to understand the mechanisms whereby elevated
      levels of ammonia in mother or fetus results in embryonic/fetal death, growth
      restriction, and developmental abnormalities; and bringing, into the attention of
      nutritionists and practitioners, the problems of excess or inadequate dietary
      intake of protein or amino acids on pregnancy outcomes in animals and humans. The
      article provides new, effective means to improve embryonic/fetal survival and
      growth in mammals.

PMID- 29466877
TI  - Behavior and health beliefs as predictors of HIV testing among women: a
      prospective study of observed HIV testing.
AB  - : Much of the research examining predictors of HIV testing has used retrospective
      self-report to assess HIV testing. FINDINGS: therefore, may be subject to recall
      bias and to difficulties determining the direction of associations. In this
      prospective study, we administered surveys to women in community clinics to
      identify predictors of subsequent observed HIV testing, overcoming these
      limitations. Eighty-three percent were tested. In the adjusted multivariable
      model, being born in the U.S., perceived benefits of testing, worries about being
      infected with HIV, having had more than 15 lifetime sexual partners, and having
      had one or more casual sexual partners in the previous three months predicted
      acceptance of testing. Perceived obstacles to testing predicted non-acceptance.
      Those who had never been tested for HIV and those tested two to five years
      previously had greater odds of test acceptance than those who had been tested
      within the last year. The findings from this study with observed testing as the
      outcome, confirm some of the results from retrospective, self-report studies.
      Participants made largely rational decisions about testing, reflecting
      assessments of their risk and their history of HIV testing. Health beliefs are
      potentially modifiable through behavioral intervention, and such interventions
      might result in greater acceptance of testing. ABBREVIATIONS: HIV: human
      immunodeficiency virus; AIDS: acquired immune deficiency syndrome; CDC: Centers
      for Disease Control and Prevention; ACASI: audio computer-assisted self
      interview; TRA: theory of reasoned action; HBM: Health Belief Model; STI:
      sexually transmitted infection; STD: Sexually Transmitted Disease; AOR: adjusted
      odds ratio; CI: confidence interval.

PMID- 29466878
TI  - Automated Computer Software Compared with Manual Measurements for CT-Based
      Urinary Stone Metrics: An Evaluation Study.
AB  - INTRODUCTION AND OBJECTIVE: Stone size guides treatment decisions, yet there is
      no standard method for measuring stone size. Prior work has shown significant
      variability in manual stone measurements. We tested a novel stone software
      program designed to provide an automated and objective comprehensive CT-based
      stone profile. METHODS: Urinary stones identified on CT imaging were manually
      measured to obtain linear size and maximal stone density (in Hounsfield unit
      [HU]). Manual stone volume was calculated using the formula 0.52 * length * width
      * height. The same stones were assessed with computer software capable of
      automatically providing stone length, density, and volume. Computer measurements
      were compared with manual measurements. RESULTS: Eighty-five stones were
      identified on 42 CT scans from 17 patients. Manual measurements showed an average
      length of 8 mm (range 1.9-21 mm), average maximal density of 686 HU (126-1492
      HU), and average stone volume of 192 mm3 (2.9-2555 mm3). Automated computer
      measurements did not differ from manual measurements for density (755 HU vs 686
      HU, p = 0.18) and volume (183 mm3 vs 192 mm3, p = 0.86. Automated length was
      slightly longer then manual length (10 mm vs 8 mm, p < 0.003). The mean percent
      differences between manual and automated metrics were 14.3% for density, 21.0%
      for volume, and 25.2% for length. CONCLUSION: Automated stone measurements can be
      accomplished quickly and precisely with dedicated software that can assess stones
      of varying size as well as stones with complex geometry. This software eliminates
      interobserver variability and offers a comprehensive stone profile with which to
      make clinical decisions.

PMID- 29466879
TI  - Pituitary adenylate cyclase-activating polypeptide ameliorates vascular
      dysfunction induced by hyperglycaemia.
AB  - BACKGROUND: Short-lasting hyperglycaemia occurs frequently in prediabetes and
      poorly controlled diabetes mellitus leading to vascular damage. Pituitary
      adenylate cyclase-activating polypeptide (PACAP) has been shown to play a
      protective role in vascular complications of diabetes; moreover, antioxidant
      effects of PACAP were also described. Therefore, we hypothesized that PACAP
      exerts protective effects in short-term hyperglycaemia-induced vascular
      dysfunctions. METHODS: After short-term hyperglycaemia, acetylcholine-induced and
      sodium nitroprusside-induced vascular relaxation of mouse carotid arteries were
      tested with a myograph with or without the presence of PACAP or superoxide
      dismutase. Potential direct antioxidant superoxide-scavenging action of pituitary
      adenylate cyclase-activating peptide was tested with pyrogallol autoxidation
      assay; furthermore, the effect of pituitary adenylate cyclase-activating peptide
      or superoxide dismutase was investigated on hyperglycaemia-associated vascular
      markers. RESULTS: PACAP administration resulted in reduced endothelial
      dysfunction after a 1-h hyperglycaemic episode. PACAP was able to restore
      acetylcholine-induced relaxation of the vessels and improved sodium nitroprusside
      induced relaxation. This effect was comparable to the protective effect of
      superoxide dismutase, but PACAP was unable to directly scavenge superoxide
      produced by autoxidation of pyrogallol. Endothelial dysfunction was associated
      with elevated levels of fibroblast growth factor basic, matrix metalloproteinase
      9 and nephroblastoma overexpressed gene proteins. Their release was reduced by
      PACAP administration. CONCLUSION: These results suggest a strong protective role
      of PACAP in the vascular complications of diabetes.

PMID- 29466881
TI  - A Comparison of Responses to Substantive Transition Prompts in Interviews With
      Children.
AB  - This study examined children's responses to two alternate prompts used to
      transition to the substantive phase of an interview. Children ( N = 401)
      experienced four scripted events and were later interviewed. After rapport
      building, half of the children were asked, "Tell me what you're here to talk to
      me about today," whereas the other half were asked, "Tell me why you're here to
      talk to me today." Children's responses were coded as informative (e.g., nouns)
      or uninformative (e.g., "don't know"). The what prompt elicited more informative
      responses than the why prompt, and 7- to 9-year-olds were more informative than 5
      to 6-year-olds regardless of the type of prompt they received. Given that the
      what prompt elicited more informative responses, the present study provides
      initial support for this phrasing when forensic interviewers transition to the
      substantive phase.

PMID- 29466880
TI  - Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin
      resistance in vitro.
AB  - BACKGROUND: Antiretroviral therapy in HIV-positive patients leads to insulin
      resistance which is central to the pathogenesis of various metabolic
      abnormalities and cardiovascular disease seen in this patient group. We have
      investigated the dose-response relationship of telmisartan, an antihypertensive,
      on adipocytes in vitro in order to determine whether it may have metabolic
      beneficial effects. METHODS: Using in vitro chronic toxicity models (3T3-F442A
      murine and primary human adipocytes), we evaluated the effects of different
      concentrations of telmisartan on adipocyte differentiation and adipogenic gene
      expression using lipid accumulation assays and real-time polymerase chain
      reaction, respectively. Adipokine secretion and expression of insulin signalling
      mediators were evaluated using enzyme-linked immunosorbent assays. RESULTS:
      Telmisartan partially reversed the deleterious effects of antiretrovirals on
      adipocyte lipid accumulation, expression of adipogenic regulators (peroxisome
      proliferator receptor-gamma and lipin 1), adipokine secretion and expression of
      the insulin signalling mediator pAktSer473. The metabolic effects of telmisartan
      followed a non-monotonic response with the maximal effect observed at 5 uM in the
      primary human adipocyte model. CONCLUSION: Telmisartan has beneficial metabolic
      effects in adipocytes in vitro, but its potential to reduce antiretroviral
      induced cardiometabolic disease in HIV-infected individuals needs to be evaluated
      in a well-designed adequately powered clinical trial.

PMID- 29466882
TI  - Emulsifying conditions and processing parameters optimisation of kenaf seed oil
      in-water nanoemulsions stabilised by ternary emulsifier mixtures.
AB  - Kenaf ( Hibiscus cannabinus L.) seed oil has been proven for its multi
      pharmacological benefits; however, its poor water solubility and stability have
      limited its industrial applications. This study was aimed to further improve the
      stability of pre-developed kenaf seed oil-in-water nanoemulsions by using food
      grade ternary emulsifiers. The effects of emulsifier concentration (1, 5, 10, 15%
      w/w), homogenisation pressure (16,000, 22,000, 28,000 psi), and homogenisation
      cycles (three, four, five cycles) were studied to produce high stability of kenaf
      seed oil-in-water nanoemulsions using high pressure homogeniser. Generally,
      results showed that the emulsifier concentration and homogenisation conditions
      had great effect ( p < 0.05) on the particle sizes, polydispersity index and
      hence the physical stability of nanoemulsions. Homogenisation parameters at
      28,000 psi for three cycles produced the most stable homogeneous nanoemulsions
      that were below 130 nm, below 0.16, and above -40 mV of particle size,
      polydispersity index, and zeta potential, respectively. Field emission scanning
      electron microscopy micrograph showed that the optimised nanoemulsions had a good
      distribution within nano-range. The optimised nanoemulsions were proved to be
      physically stable for up to six weeks of storage at room temperature. The results
      from this study also provided valuable information in producing stable kenaf seed
      oil nanoemulsions for the future application in food and nutraceutical
      industries.

PMID- 29466883
TI  - Inequality and poverty: Toxic issues that impact on children's health and
      opportunities.

PMID- 29466884
TI  - Fertility 2018 4-6th JANUARY 2018 ACC Liverpool British Fertility Society Society
      for Reproduction and Fertility Association of Clinical Embryologists.

PMID- 29466885
TI  - Intralesional therapy as a treatment for locoregionally metastatic melanoma.
AB  - INTRODUCTION: The emergence of novel intralesional therapies have dramatically
      changed the treatment landscape for melanoma. The heterogeneous presentation of
      melanoma continues to pose challenges for clinicians, especially when dealing
      with advanced locoregional disease. Intralesional therapies have the benefit of
      causing local tumor destruction, while minimizing systemic toxicity. Moreover,
      the integration of immunotherapeutic agents into intralesional compounds has
      resulted in the additional benefit of a bystander effect, whereby untreated
      distant lesions also derive a benefit from treatment. Intralesional therapy has
      assumed an important role in the management of unresectable, locoregional disease
      for melanoma. Areas covered: Multiple intralesional agents have been studied over
      the years, with only a few demonstrating promising results. This review will
      provide an overview of the different intralesional agents for melanoma.
      Mechanisms of action, clinical efficacy, and side effects will be the primary
      focus. Expert commentary: Treatment options for advanced melanoma continue to
      evolve. Attractive new therapies delivered by an intralesional route has
      demonstrated promising results, with minimal side effects. The ideal treatment
      strategy for melanoma will remain a multimodal approach; intralesional therapy
      provides an additional tool in the treatment armamentarium for melanoma.

PMID- 29466886
TI  - Proteomic approaches to identify blood-based biomarkers for depression and
      bipolar disorders.
AB  - INTRODUCTION: Major depressive disorder (MDD) and bipolar disorder (BD) are
      leading causes of disability worldwide, yet many people remain undiagnosed, are
      misdiagnosed, and/or ineffectively treated. Diagnosis relies on the clinical
      assessment of symptoms, and there is currently no molecular or brain-imaging
      diagnostic test available. Identifying and validating protein biomarkers could
      provide a more accurate and objective means of diagnosis. Areas covered:
      Proteomics is a powerful tool that enables the identification and quantification
      of novel candidate biomarkers of disease. In this review, we discuss the role of
      proteomic technologies in biomarker discovery and validation, peripheral blood as
      a source of protein biomarkers, statistical methods for analyzing proteomic data,
      and some existing challenges in the field. We also review a selection of
      previously published studies focused on identifying blood-based diagnostic
      protein biomarkers of MDD and BD within a ten-year period. Expert commentary:
      Proteomic studies have led to the identification of numerous potential biomarkers
      of MDD and BD. However, clinical validation and translation into clinical
      practice have not yet been achieved. Conducting large-scale validation studies
      and addressing various factors that limit the reproducibility of the proteomic
      findings are key to ensure that robust and reliable biomarker tests are developed
      and clinically validated.

PMID- 29466887
TI  - Access to anti-cancer drugs in India: is there a need to revise reimbursement
      policies?
AB  - BACKGROUND: The aim of this study was to examine the access of Indian cancer
      patients to optimum cancer care under selected government schemes by reviewing
      reimbursement schemes for cancer care in India. METHODS: All cancer care
      reimbursement schemes in India were identified and three highly utilized schemes
      (VAS, RAS, CMCHS) were selected. Quality of breast, colorectal, lung, head &
      neck, and gastric cancer care was reviewed with respect to NCCN guidelines.
      Direct medical costs and shortage of budget in reimbursed amounts were calculated
      for each listed chemotherapy regimen. RESULTS: Medical oncology practice
      following the schemes' formularies is inferior to recommendations by the NCCN
      guidelines. Innovative treatment (targeted therapies) like trastuzumab,
      pertuzumab (breast), bevacizumab, cetuximab, panitumumab (colorectal), erlotinib,
      gefitinib, crizotinib, and nivolumab (lung) are either not reimbursed (VAS,
      CMCHS) or partially reimbursed (RAS). Average shortage of budget was found to be
      43% (breast), 55% (colorectal), 74% (lung), 7% (head & neck), and 51% (gastric
      cancer). CONCLUSIONS: Policy makers should consider addition of newer treatments,
      exclusion of sub-optimal treatments, increments in per patient budget and
      optimization of supportive care, which may contribute to improvements in survival
      and quality of life for Indian cancer patients.

PMID- 29466888
TI  - Increased incidence or recurrence of hepatocellular carcinoma in hepatitis C
      virus cirrhotic patients treated with direct-acting antivirals: myth or fact?

PMID- 29466889
TI  - Downregulated N-acetylglucosaminyltransferase III is involved in attenuating
      trophoblast migration and invasion under hypoxia-reoxygenation condition.
AB  - OBJECTIVE: Many studies have confirmed that N-acetylglucosaminyltransferase III
      (GnT-III) is correlated with tumor invasion and metastasis. However, the
      expression of GnT-III and its role in normal pregnancy and preeclampsia (PE) has
      not been reached. So the primary objective of this study is to determine GnT-III
      expression in normal pregnancy and whether its expression is vulnerable to
      oxidative stress in the trophoblast cells. METHODS: Human first trimester villous
      tissues from normal pregnancies and third trimester placentas from pregnancies
      with or without preeclampsia (PE) were used for the detection of GnT-III
      expression. Human first trimester extravillous trophoblast cell line (HTR8/SVneo)
      exposed to hypoxia/reoxygenation (H/R) condition was employed as an oxidative
      stress model in vitro to investigate the expression of GnT-III. RESULTS: GnT-III
      was strongly expressed in cytotrophoblast (CTBs), syncytiotrophoblast (STBs) and
      the trophoblast columns (TCs) of human placental villi, and decidual cells in the
      maternal decidua. The expression of GnT-III was decreased in PE placentas
      compared with the normal control placentas. In addition, GnT-III was found to
      have decreased expression in H/R-exposed HTR8/SVneo cells, and the invasive and
      migratory abilities of HTR8/SVneo cells were attenuated, too. CONCLUSIONS: These
      findings suggest that GnT-III is an important regulator at the maternal-fetal
      interface during early pregnancy. Excessive oxidative stress can decrease GnT-III
      expression in trophoblast and the decreased expression of GnT-III may be involved
      in the development of preeclampsia.

PMID- 29466890
TI  - Selective drug delivery approaches to lesioned brain through blood brain barrier
      disruption.
AB  - INTRODUCTION: The development of therapeutics for central nervous system (CNS)
      disorders is still considered a challenging area in drug development due to
      insufficient translocation through the blood-brain barrier (BBB). Under normal
      conditions, BBB restrict the penetration of more than 98% of blood-borne
      molecules including drugs to the CNS. However, recent research findings have
      proven that the nature of the BBB is altered in several neurological conditions.
      This complexity encourages revisiting drug delivery strategies to the CNS as this
      can give a wide range of opportunities for CNS drug development. Areas covered:
      This review focuses on nanotechnology-based drug delivery platforms designed for
      selective recruitment into the lesioned brain by taking advantages of BBB
      disruption that is associated with certain neurological conditions. Expert
      opinion: Current CNS therapeutic strategies do not fully address the
      pathophysiological adaptation of BBB in their design. The lack of selective
      delivery to the brain lesions has been the culprit behind the failure of many CNS
      therapeutics. This highlighted the need for smart designs of advanced drug
      delivery systems that take advantage of BBB structural changes in CNS diseases.
      Recently, promising examples have been reported in this area, however, more work
      is still required beyond the preclinical testing.

PMID- 29466891
TI  - Proenkephalin and risk of developing chronic kidney disease: the Prevention of
      Renal and Vascular End-stage Disease study.
AB  - BACKGROUND: Proenkephalin (pro-ENK) was recently found to be associated with low
      estimated glomerular filtration rate (eGFR). The association of pro-ENK with
      urinary albumin excretion (UAE), another marker for chronic kidney disease (CKD),
      has not been investigated. We examined the association of pro-ENK with eGFR and
      UAE as markers of CKD. METHODS: We included 4375 subjects of the Prevention of
      Renal and Vascular End-Stage Disease (PREVEND) study. CKDeGFR was defined as
      development of eGFR <60 ml/min/1.73 m2 and CKDUAE as albuminuria >30 mg/24 h.
      RESULTS: Baseline median pro-ENK was 52.2 (IQR: 44.9-60.5) pmol/L. After a median
      follow-up of 8.4 (IQR: 7.9-8.9) years, 183 subjects developed CKDeGFR and 371
      developed CKDUAE. The association of pro-ENK with CKDeGFR was modified by sex
      (Pinteraction < 0.1), in such a way that after adjustment, the association only
      remained significant in men (adjusted hazard ratio per SD increase in 10log
      transformed pro-ENK, 1.65; 95% CI: 1.15-2.36) and not in women (0.83; 0.58-1.20).
      No significant association was observed between pro-ENK and CKDUAE risk (0.83;
      0.58-1.20). CONCLUSIONS: High pro-ENK is associated with increased risk of
      CKDeGFR in men, but not in women. No association of pro-ENK with CKDUAE was
      observed. These results should be interpreted with caution, since residual
      confounding and potential overfitting of models could have influenced the
      results.

PMID- 29466892
TI  - Can etanercept treatment failure in moderate-to-severe psoriasis be overcome by
      addition of low-dose methotrexate? A single-center experience.
AB  - BACKGROUND: Loss of efficacy is a major anticipated shortcoming of utilizing
      etanercept and other biologic agents for treating moderate-to-severe psoriasis.
      PURPOSE: To investigate the addition of low-dose methotrexate as a means to
      increase etanercept drug survival. METHODS: Eleven patients with severe psoriasis
      were switched to a combination of etanercept with low-dose methotrexate therapy,
      after a primary or secondary failure with etanercept treatment as a monotherapy.
      Time period for cessation of combined treatment and side effects were documented.
      The effect of previous methotrexate treatment was investigated. RESULTS: Six men
      and five women were included in the study. The patients had moderate-to-severe
      psoriasis with a mean baseline Psoriasis Area and Severity Index (PASI) of 29
      (median 25). Median duration of etanercept monotherapy was 12 months. Median
      duration of combined treatment was 13 months. Combined treatment was discontinued
      in three patients due to side effects. Previous failure of methotrexate
      monotherapy did not alter the duration of the combined treatment. CONCLUSION:
      Addition of low-dose methotrexate may rescue etanercept therapy after failure of
      etanercept monotherapy in patients with moderate-to-severe psoriasis.

PMID- 29466893
TI  - Physical Function in U.S. Older Adults Compared With Other Populations: A
      Multinational Study.
AB  - OBJECTIVE: We compare physical performance from three U.S. national surveys and
      nationally representative surveys in England, Taiwan, and Costa Rica. METHOD: For
      each performance test, we use local mean smoothing to plot the age profiles by
      sex and survey wave and then fit a linear regression model to the pooled data,
      separately by sex, to test for significant differences across surveys controlling
      for age and height. RESULTS: Age profiles of performance vary across U.S.
      surveys, but levels of lung function (peak expiratory flow) and handgrip strength
      in the United States are as high as they are in the other three countries.
      Americans also perform as well on the chair stand test as the English and Costa
      Ricans, if not better, but exhibit slower gait speed than the English at most
      ages. DISCUSSION: With the exception of walking speed, we find little evidence
      that older Americans have worse physical performance than their peers.

PMID- 29466894
TI  - A preliminary study on topical ozonated oil in the therapeutic management of
      atopic dermatitis in murine.
AB  - OBJECTIVE: To explore whether ozonated oil recovery atopic dermatitis (AD) via
      immunoregulation. METHODS: Mice were repeatedly challenged with the triplex
      allergens of staphylococcal enterotoxin B, ovalbumin and calcipotriol ointment on
      the back to develop AD lesions, and were treated with ozonated oil. The lesional
      skins were scanned by reflectance confocal microscopy to measure the thickness of
      epidermis. The skin tissues were stained. Th1-type and Th2-type cytokines in
      serum and in tissues were detected by ELISA and real-time PCR, respectively.
      RESULTS: Ozonated oil significantly inhibited inflammation and healed the lesions
      in 7 d. Ozonated oil inhibited NGF expression as compared to the groups treated
      with vehicle or PBS (p < .01).The serum proteins and lesional transcripts of Th2
      cytokines including IL-4 and IL-31 were lower in the ozonated oil treated group
      than the groups treated with vehicle or PBS (p < .05). The IL-10 level was
      increased with treatment of ozonated oil (p < .01). On the other hand, the
      expressions of Th1 cytokines including IL-2, TNF-alpha, and IFN-gamma in the
      serum were not regulated by ozonated oil. CONCLUSIONS: Our results showed that
      ozonated oil could suppress inflammation in an AD murine via decreasing Th2
      dominant cytokines response and increasing IL-10 expression. These suggest that
      ozonated oil may be a potential remedy for AD.

PMID- 29466895
TI  - Altered plasma-type gelsolin and amyloid-beta in neonates with hypoxic-ischaemic
      encephalopathy under therapeutic hypothermia.
AB  - Hypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication
      responsible for ~23% of all neonatal deaths. Also, 30-70% of these patients will
      suffer lifetime disabilities, including learning impairment, epilepsy or cerebral
      palsy. However, biomarkers for HIE screening, or monitoring disease progression
      are limited. Herein, we sought to evaluate the clinical usefulness of plasma-type
      gelsolin (pGSN) and amyloid-beta (Abeta) 40 and 42 as prognostic biomarkers for
      HIE. pGSN has been previously suggested as a feasible marker in other brain
      injuries and amyloid-beta 40 and 42 are classically assessed in neurodegenerative
      diseases. However, to our knowledge, they have not been previously assessed in
      HIE patients. We have analyzed plasma pGSN and Abeta 40 and 42 levels in 55
      newborns (16 controls, 16 mild and 23 moderate-severe HIE) at birth, during 72 h
      of therapeutic hypothermia, a gold-standard treatment for HIE, and 24 h after
      hypothermia. Abeta levels were lower in HIE patients, and pGSN levels were
      progressively reduced in mild and moderate-severe HIE patients. The fact that
      pGSN reductions could predict the severity of HIE and significantly correlated
      with the time to undergo hypothermia supports the prognostic value of plasmatic
      pGSN. Further studies are warranted to investigate the role of pGSN in neonatal
      HIE.

PMID- 29466896
TI  - Reentry Devices for Lamella Neofenestration During Endovascular Aortic Repair of
      Chronic Type B Aortic Dissection.
AB  - PURPOSE: To present a technique that creates a neofenestration in the dissecting
      lamella of chronic aortic dissections using standard or intravenous ultrasound
      (IVUS)-guided reentry devices. TECHNIQUE: To create a neofenestration, a standard
      or IVUS-guided reentry device is deployed in either the true or false aortic
      lumen while a balloon is simultaneously inflated in the opposite lumen to
      stabilize the lamella, provide needle counterforce, and prevent displacement of
      the lamella away from the reentry needle. Once the lamella is perforated and a
      guidewire passed across the 2 lumens, progressive dilation of the neofenestration
      is performed to establish persistent communication. CONCLUSION: The balloon
      supported lamella neofenestration technique involving off-label application of
      two currently available reentry devices can be applied to endovascular treatment
      chronic aortic dissections. While the technique will definitely not become a
      standard of practice, it provides a safe, effective, and readily available option
      for endovascular management of those patients with complex chronic aortic
      dissections requiring bailout maneuvers or elective treatment.

PMID- 29466897
TI  - Patients Older Than 80 Years Can Reach Their Normal Life Expectancy After
      Abdominal Aortic Aneurysm Repair: A Comparison Between Endovascular Aneurysm
      Repair and Open Surgery.
AB  - PURPOSE: To investigate the long-term outcomes of endovascular aneurysm repair
      (EVAR) and open surgical repair (OSR) of infrarenal abdominal aortic aneurysm in
      octogenarian patients and to compare them with the overall expected survival
      based on a sex- and age-matched German population. METHODS: A total of 177
      patients (median age 82 years; 149 men) >=80 years old (range 80-92) who
      underwent primary elective repair of an infrarenal aortic aneurysm (>=5 cm)
      between 1998 and 2015 were identified in a database search. Two groups of
      patients were formed based on the type of procedure: 131 EVAR patients (median
      age 83 years; 114 men) and 46 OSR patients (median age 82 years; 35 men).
      RESULTS: The median follow-up was 5 years for the OSR group and 4.5 years for the
      EVAR group. Kaplan-Meier analysis showed no significant difference in survival
      between the EVAR and OSR groups at 78 months. The observed survival of all study
      patients was not statistically different from the expected survival of a sex- and
      age-matched German population, which was true separately for women and men.
      CONCLUSION: The patients in this study seemed to reach normal life expectancy in
      comparison to the age- and sex-matched general population with a similar
      cumulative survival in both study groups over 5 years of follow-up.

PMID- 29466898
TI  - The antiepileptic and neuroprotective effect of the Buxus hyrcana Pojark
      hydroethanolic extract against the pentylentetrazol induced model of the seizures
      in the male rats.
AB  - AIMS: The genus Buxus grows up widespread in Europe and Western Asia. It is an
      important traditional plant that has been used in the treatment of many
      illnesses. In the present study, the effect of hydroethanolic extract of Buxus
      hyrcana Pojark (BHP) on the animal model of seizure was studied. MATERIALS AND
      METHODS: In this experimental study, 42 male Wistar rats weighing 220-250 g were
      randomly selected and were divided into experimental and control groups (six rats
      per group). The experimental groups were treated by the intraperitoneal (i.p.)
      single injection of 150, 300, 450, 600 and 750 mg kg-1 of hydroalcoholic extracts
      of BHP. The control negative group received normal saline (0.9%) and the control
      positive group received phenobarbital (30 mg kg-1, i.p.) pre-treatment. Thirty
      minutes after the treatments, the seizure behaviors were evaluated by the
      pentylenetetrazole (PTZ) (70 mg kg-1, i.p.) challenge. In addition, after the
      experiment, the rats were put to death and their brains were removed for the
      histological study. RESULTS: The ANOVA demonstrated that compared to the control
      group, all the BHP doses delayed the initiation and duration of the tonic,
      colonic and tonic-colonic seizures and significantly reduced the tonic and
      colonic seizures (p < 0.001). Furthermore, the administration of all five doses
      of the extract significantly prevented the production of the dark neurons (p <
      0.001) in different areas of the hippocampus compared to PTZ group. CONCLUSION:
      We can conclude that the BHP extract has beneficial effects for the prevention of
      the PTZ induced seizure.

PMID- 29466899
TI  - Kristeller maneuvers or fundal pressure and maternal/neonatal morbidity:
      obstetric and judicial literature review.
AB  - AIM: A significant amount of data concerning maternal-fetal damage arising from
      the exertion of Kristeller maneuvers (KMs) or fundal pressure (FP) go unreleased
      due to medicolegal implications. MATERIALS AND METHODS: For this reason, the
      paper gathers information as to the real magnitude of litigation related to FP
      induced damages and injuries. The authors have undertaken a research in order to
      include general search engines (PubMed-Medline, Cochrane, Embase, Google,
      GyneWeb) and legal databases (De Jure, Italian database of jurisprudence daily
      update; Westlaw, Thomson Reuters, American ruling database and Bailii, UK Court
      Ruling Database). RESULTS: Results confirm said phenomenon to be more wide
      ranging than it appears through official channels. Several courts of law, both in
      the United States of America (USA) and in European Union (EU) Member States as
      well, have ruled against the use of the maneuver itself, assuming a stance
      conducive to a presumption of guilt against those doctors and healthcare
      providers who resorted to KMs or FP during deliveries. Given how rife FP is in
      mainstream obstetric practice, it is as if there were a wide gap between
      obstetric real-life and what official jurisprudence and healthcare institutions
      sanctioned official practices are. CONCLUSION: The authors think that it would be
      desirable to draft specifically targeted guidelines or recommendations on
      maneuvers during vaginal delivery, in which to point out exactly what kinds of
      maneuvering techniques are to be absolutely banned and what maneuvers are to be
      allowed, and under what conditions their application can be considered
      appropriate.

PMID- 29466900
TI  - Influence of MMP inhibitor GM6001 loading of fibre coated polypropylene meshes on
      wound healing: Implications for hernia repair.
AB  - Polypropylene meshes are standard for hernia repair. Matrix metalloproteinases
      play a central role in inflammation. To reduce the inflammatory response and
      improve remodelling with an associated reduction of hernia recurrence, we
      modified polypropylene meshes by nanofibre coating and saturation with the broad
      spectrum matrix metalloproteinase inhibitor GM6001. The aim was to modulate the
      inflammatory reaction, increase collagen deposition and improve mesh
      biointegration. Polypropylene meshes were surface-modified with star-configured
      NCO-sP(EO -stat-PO) and covered with electrospun nanofibres (polypropylene-nano)
      and GM6001 (polypropylene-nano-GM). In a hernia model, defects were reconstructed
      with one of the meshes. Inflammation, neovascularization, bio-integration,
      proliferation and apoptosis were assessed histologically, collagen content and
      gelatinases biochemically. Mesh surface modification resulted in higher
      inflammatory response compared to polypropylene. Pro-inflammatory matrix
      metalloproteinase-9 paralleled findings while GM6001 reduced matrix
      metalloproteinase-9 significantly. Significantly increased matrix
      metalloproteinase-2 beneficial for remodelling was noted with polypropylene-nano
      meshes. Increased vascular endothelial growth factor, neo-vascularization and
      collagen content were measured in polypropylene-nano-meshes compared to
      polypropylene. GM6001 significantly reduced myofibroblasts. This effect ended
      after d14 due to engineering limitations with release of maximal GM6001 loading.
      Nanofibre-coating of polypropylene-meshes confers better tissue vascularization
      to the cost of increased inflammation. This phenomenon can be only partially
      compensated by GM6001. Future research will enable higher GM6001 uptake in nano
      coated meshes and may alter mesh biointegration in a more pronounced way.

PMID- 29466901
TI  - Modified ISTH pregnancy-specific DIC score in parturients with liver rupture:
      population-based case series.
AB  - OBJECTIVES: Liver rupture and hematoma are rare life-threatening complications of
      pregnancy. The aims of the current study are to: (1) characterize in a population
      based study all cases of liver hematoma and/or rupture; and (2) validate the
      utility of the International Society on Thrombosis and Haemostasis (ISTH)
      modified pregnancy specific disseminated intravascular coagulation (DIC) score in
      those cases. STUDY DESIGN: A retrospective cohort study including all patients
      with liver subcapsular hematoma or rupture between the years 1996 and 2012 was
      conducted. Information on maternal characteristics, clinical presentation,
      diagnostic studies, therapeutic modalities, as well as maternal and fetal
      outcomes was collected. The pregnancy-specific modified ISTH DIC scores were
      calculated from admission to discharge, a score >26 is suggestive of DIC.
      RESULTS: Out of 175,000 births in our database, seven patients were identified
      with liver rupture or subcapsular hematoma, representing a prevalence of
      4:100,000 deliveries. Of those, six had liver rupture and one had subcapsular
      liver hematoma. One patient died of hemorrhagic shock. Four patients underwent
      surgical liver packing and one also underwent hepatic artery ligation. Four out
      of seven patients were diagnosed during the immediate postpartum period with
      severe features of preeclampsia or with hemolysis, elevated liver enzymes, and
      low platelet count (HELLP) syndrome. Modified ISTH pregnancy-specific DIC scores
      were calculated for five out of seven patients, and three (60%) had a score
      higher than 26. Patients with higher scores received more blood product
      transfusions, had longer hospitalizations, and their neonates had lower 1 and 5
      minutes Apgar scores. CONCLUSIONS: Elevated pregnancy-specific modified ISTH DIC
      score (>26) in patients with liver hematoma or rupture was associated with
      adverse maternal and neonatal outcomes and appeared to perform well in
      distinguishing high and low-risk cases. Postpartum preeclampsia may be associated
      with severe features and a more complicated disease course.

PMID- 29466902
TI  - Aberrant left subclavian artery occlusion in right-sided aortic artery associated
      with left cerebral infarction: A case report.
AB  - Purpose Right-sided aortic arch is a rare vessel anomaly with an incidence of
      0.1% worldwide. Supra-aortic branches form a mirror image of the left-sided
      aortic arch or an aberrant left subclavian artery associated with Kommerell
      diverticulum. Most patients are diagnosed by a difference in blood pressure in
      each upper extremity or by the presence of left subclavian steal syndrome in
      their younger age. The diagnosis of onset of ischemic stroke in middle age is
      rare. Methods We present the case of a female patient who presented with an
      ischemic stroke in the left posterior circulation area. She had no history of
      congenital heart malformation. We performed head magnetic resonance imaging,
      cerebral angiography, and enhanced computed tomography of the aortic arch and
      major branches. Results The patient had a right-sided aortic arch and an aberrant
      left subclavian artery. The left subclavian artery was occluded at the proximal
      portion with a fibrous string. Collateral flow in the anterior cervical
      subcutaneous area supported left limb perfusion. Conclusion An atheromatous
      change reduced shunt flow via collateral networks at the anterior cervical
      region. Congenital subclavian steal supported the ischemic stroke.

PMID- 29466905
TI  - Corrigendum.
AB  - Quantitative assessment of demyelination in ischemic stroke in vivo using
      macromolecular proton fraction mapping. Khodanovich MY, Kisel AA, Akulov AE et
      al. J Cereb Blood Flow Metab. Epub ahead of print 26 January 2018. DOI:
      10.1177/0271678X18755203 . An error appears in Figure 6 of the above article. The
      blue point with the label "1 day" should not appear in the figure. The correct
      Figure 6 is shown below.

PMID- 29466903
TI  - Complications of endovascular treatment for intracranial aneurysms: Management
      and prevention.
AB  - Endovascular coiling for intracranial aneurysms has become an accepted treatment
      with good clinical results and provides adequate protection against rebleeding
      and rupture of aneurysms. However, despite the experience, preparation, or skill
      of the physician, complications during endovascular treatment still occur. The
      main complications of endovascular coiling are: procedural aneurysmal
      perforations by the microcatheter, micro-guidewire, or coil, and thromboembolic
      events. Such situations are unexpected, complex, and can have devastating
      consequences. In this article, we present a comprehensive review of the two most
      common complications, aneurysmal perforation and thromboembolism during
      endovascular coiling, and how we can prevent or overcome these complications to
      achieve a satisfactory outcome. In addition, as the flow diverter has been become
      an important tool for management of large, wide necked, and other anatomically
      challenging aneurysms, we also describe complications stemming from the use of
      the tool, which remains a novel treatment option for complex aneurysms.

PMID- 29466904
TI  - Effect of metal artifact reduction software on image quality of C-arm cone-beam
      computed tomography during intracranial aneurysm treatment.
AB  - Background and purpose C-arm cone-beam computed tomography (CBCT) has the
      drawback that image quality is degraded by artifacts caused by implanted metal
      objects. We evaluated whether metal artifact reduction (MAR) prototype software
      can improve the subjective image quality of CBCT images of patients with
      intracranial aneurysms treated with coils or clips. Materials and methods Forty
      four patients with intracranial aneurysms implanted with coils (40 patients) or
      clips (four patients) underwent one CBCT scan from which uncorrected and MAR
      corrected CBCT image datasets were reconstructed. Three blinded readers evaluated
      the image quality of the image sets using a four-point scale (1: Excellent, 2:
      Good, 3: Poor, 4: Bad). The median scores of the three readers of uncorrected and
      MAR-corrected images were compared with the paired Wilcoxon signed-rank and inter
      reader agreement of change scores was assessed by weighted kappa statistics. The
      readers also recorded new clinical findings, such as intracranial hemorrhage,
      air, or surrounding anatomical structures on MAR-corrected images. Results The
      image quality of MAR-corrected CBCT images was significantly improved compared
      with the uncorrected CBCT image ( p < 0.001). Additional clinical findings were
      seen on CBCT images of 70.4% of patients after MAR correction. Conclusion MAR
      software improved image quality of CBCT images degraded by metal artifacts.

PMID- 29466906
TI  - Melanin Bleaching With Warm Hydrogen Peroxide and Integrated Immunohistochemical
      Analysis: An Automated Platform.
AB  - OBJECTIVE: Diagnosing melanocytic lesions is among the most challenging problems
      in the practice of pathology. The difficulty of physically masking melanin
      pigment and the similarity of its color to commonly used chromogens often
      complicate examination of the cytomorphology and immunohistochemical staining
      results for tumor cells. Melanin bleach can be very helpful for histopathological
      diagnosis of heavily pigmented melanocytic lesions. Although various
      depigmentation methods have been reported, no standardized methods have been
      developed. This study developed a fully automated platform that incorporates
      hydrogen peroxide-based melanin depigmentation in an automated
      immunohistochemical analysis. METHODS AND MATERIALS: The utility of the method
      was tested in 1 cell block of malignant melanoma cells in pleural effusion, 10
      ocular melanoma tissue samples, and 10 cutaneous melanoma tissue samples. Our
      results demonstrated that the proposed method, which can be performed in only 3
      hours, effectively preserves cell cytomorphology and immunoreactivity. RESULTS:
      The method is particularly effective for removing melanin pigment to facilitate
      histopathological examination of cytomorphology and for obtaining an unmasked
      tissue section for immunohistochemical analysis.

PMID- 29466907
TI  - Teaching forensic pathology to undergraduates at Zhongshan School of Medicine.
AB  - Producing qualified forensic pathological practitioners is a common difficulty
      around the world. In China, forensic pathology is one of the required major
      subspecialties for undergraduates majoring in forensic medicine, in contrast to
      forensic education in Western countries where forensic pathology is often
      optional. The enduring predicament is that the professional qualities and
      abilities of forensic students from different institutions vary due to the lack
      of an efficient forensic pedagogical model. The purpose of this article is to
      describe the new pedagogical model of forensic pathology at Zhongshan School of
      Medicine, Sun Yat-sen University, which is characterised by: (a) imparting a
      broad view of forensic pathology and basic knowledge of duties and tasks in
      future careers to students; (b) educating students in primary skills on legal and
      medical issues, as well as advanced forensic pathological techniques; (c)
      providing students with resources to broaden their professional minds, and
      opportunities to improve their professional qualities and abilities; and (d)
      mentoring students on occupational preparation and further forensic education. In
      the past few years, this model has resulted in numerous notable forensic students
      accomplishing achievements in forensic practice and forensic scientific research.
      We therefore expect this pedagogical model to establish the foundation for
      forensic pathological education and other subspecialties of forensic medicine in
      China and abroad.

PMID- 29466908
TI  - Double suicide in modern Japan (in Kanagawa prefecture): Comparison with those in
      post-war Japan and other countries.
AB  - Double-suicide cases have long been common in Japan, particularly among lovers.
      Classical studies conducted in the 1950s are well known. According to a report by
      Ohara, the double-suicide rate in Japan was recorded as 3.1% in 1954.
      Nevertheless, recent tendencies have not been reported. To assess the latest
      trends of double suicide, extensive studies were conducted in a populous area of
      Kanagawa, Japan, during 1999-2011. Suicides during the period in the domestic
      area claimed 23,195 victims. In all, 82 cases of double suicide were extracted,
      with 170 victims, meaning that double suicides occurred with incidence of 0.73%
      among all suicides. The mean age and standard deviation were 51.6+/-16.1 years,
      with 83 men and 87 women. The suicide-partner relationships included 40 cases
      (48.8%) of married couples, 13 (15.9%) of unmarried lovers, and 10 (12.2%) of
      elderly woman and her son/daughter dyads. No significant difference was found
      from Western countries in the incidence of double-suicide cases in Japan, except
      for a higher incidence of suicide involving elderly people and their
      sons/daughters. The traditional style of double suicide by lovers has become less
      frequent in modern Japanese society, presumably because of changing marriage
      styles and values.

PMID- 29466909
TI  - Skin Conductance Responses to Masked Emotional Faces Are Modulated by Hit Rate
      but Not Signal Detection Theory Adjustments for Subjective Differences in the
      Detection Threshold.
AB  - The biological preparedness model suggests that survival-related visual cues
      elicit physiological changes without awareness to enable us to respond to our
      environment. Previous studies have reported some evidence for this effect. In the
      current article, we argue that this evidence is subject to methodological
      confounds. These include the use of a universal masked presentation threshold,
      the employment of hit rates (HRs) to measure meta-awareness, and the assertion of
      overall guess-level target detection using nonsignificance. In the current
      report, we address these issues and test whether masked emotional faces can
      elicit changes in physiology. We present participants with subjectively adjusted
      masked angry, fearful, happy, and neutral faces using HRs and signal detection
      theory. We assess detection performance using a strict Bayesian criterion for
      meta-awareness. Our findings reveal that HR adjustments in the detection
      threshold allow higher skin conductance responses to happy, fearful, and angry
      faces, but that this effect could not be reported by the same participants when
      the adjustments were made using signal detection measures. Combined these
      findings suggest that very brief biologically relevant stimuli can elicit
      physiological changes but cast doubt to the extent that this effect can occur in
      response to truly unconscious emotional faces.

PMID- 29466910
TI  - The Role of Ventral Tegmental Area Gamma-Aminobutyric Acid in Chronic Neuropathic
      Pain after Spinal Cord Injury in Rats.
AB  - Spinal cord injury (SCI) frequently results in chronic neuropathic pain (CNP).
      However, the understanding of brain neural circuits in CNP modulation is unclear.
      The present study examined the changes of ventral tegmental area (VTA) putative
      GABAergic and dopaminergic neuronal activity with CNP attenuation in rats. SCI
      was established by T10 clip compression injury (35 g, 1 min) in rats, and
      neuropathic pain behaviors, in vivo extracellular single-cell recording of
      putative VTA gamma-aminobutyric acid (GABA)/dopamine neurons, extracellular GABA
      level, glutamic acid decarboxylase (GAD), and vesicular GABA transporters (VGATs)
      were measured in the VTA, respectively. The results revealed that extracellular
      GABA level was significantly increased in the CNP group (50.5 +/- 18.9 nM)
      compared to the sham control group (10.2 +/- 1.7 nM). In addition, expression of
      GAD65/67, c-Fos, and VGAT exhibited significant increases in the SCI groups
      compared to the sham control group. With regard to neuropathic pain behaviors,
      spontaneous pain measured by ultrasound vocalizations (USVs) and evoked pain
      measured by paw withdrawal thresholds showed significant alteration, which was
      reversed by intravenous (i.v.) administration of morphine (0.5-5.0 mg/kg). With
      regard to in vivo electrophysiology, VTA putative GABAergic neuronal activity
      (13.6 +/- 1.7 spikes/sec) and putative dopaminergic neuronal activity (2.4 +/-
      0.8 spikes/sec) were increased and decreased, respectively, in the SCI group
      compared to the sham control group. These neuronal activities were reversed by
      i.v. administration of morphine. The present study suggests that chronic increase
      of GABAergic neuronal activity suppresses dopaminergic neuronal activity in the
      VTA and is responsible for negative emotion and motivation for attenuation of SCI
      induced CNP.

PMID- 29466911
TI  - Goal setting for weight-related behavior change in children: An exploratory
      study.
AB  - BACKGROUND: There is an absence of studies exploring different goal-setting
      appraches and none which have examined the use of proxy goal-setting by parents
      for their children. AIM: To explore how proficient parents are in setting health
      behaviour goals for their children according to SMART (specific, measurable,
      achievable, realistic and time-framed) goal principles. A secondary aim was to
      examine associations between goal setting and change in health behaviors.
      METHODS: Participants were parents and children taking part in one of two trials
      incorporating goal setting. Study 1 ( Time2bHealthy) was an online program for
      parents of preschoolers ( n = 36) and Study 2 ( HIKCUPS) was a three-arm face-to
      face trial examining a parent-centered dietary intervention, (Study2Diet); a
      child-centered physical activity intervention, (Study2PA); or combination of both
      (Study2Combo) ( n = 83). Goals were coded on five 'SMART' principles. Goals were
      scored 1 or 0 for each principle (1 indicated the principle was met and 0, not
      met). The total maximum score for each goal was 5. Mean total goal-score and
      means for each SMART principle were calculated. RESULTS: Mean (and standard
      deviation) goal setting scores for Study 1 were 3.84 (0.61), Study2Diet 2.17
      (1.33), Study2PA 3.18 (1.45) and Study2Combo 2.24 (1.30). Goal-scores were
      significantly higher for Study 1 than Study 2 ( p < 0.001). In Study2Diet, goal
      setting was significantly associated with greater reduction in energy intake ( p
      = 0.019). CONCLUSIONS: Goal-scores were highest in Study 1, which used a
      supported online format for setting goals. Parents were better at setting
      physical activity goals, but these goals did not translate into improvements in
      physical activity behavior. Goals set by parents may be useful in energy intake
      reduction, however further research is required to determine benefits for weight
      status or physical activity.

PMID- 29466912
TI  - Radial shaft fracture obliquity as a predictor of distal radioulnar joint
      instability.
AB  - : We assessed whether radial shaft fracture obliquity measurements on radiographs
      could predict intra-operative distal radioulnar joint instability. We also
      clinically validated previously described predictors of distal radioulnar joint
      instability, which included a fracture line within 7.5 cm of the lunate fossa,
      radial shortening >5 mm, and ulna styloid fracture. We retrospectively analysed
      the radiographs of all surgically managed patients in our unit with radial shaft
      fractures from 2006 through 2016. The degree of obliquity was analysed on the
      basis of the maximum fracture-line angle in either the coronal or the sagittal
      plane. A radial shaft fracture obliquity >30 degrees  is predictive of distal
      radioulnar joint instability ( P = 0.001). Radial fracture shaft obliquity >30
      degrees  was the most sensitive radiological parameter (76%) for predicting
      distal radioulnar joint instability. Oblique radial shaft fractures appear to be
      associated with increased incidence of distal radioulnar joint instability. This
      radiologic parameter may be used together with established parameters in
      predicting distal radioulnar joint instability for surgical treatment. LEVEL OF
      EVIDENCE: III.

PMID- 29466913
TI  - Screening for cognitive impairment in SLE using the Self-Administered
      Gerocognitive Exam.
AB  - Objective Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease
      that can affect the central nervous system in multiple ways, including causing
      cognitive dysfunction. Cognitive dysfunction is a common complaint of SLE
      patients yet diagnosis is challenging, time consuming, and costly. This study
      evaluated the Self-Administered Gerocognitive Exam (SAGE) as a screening test for
      cognitive impairment in a cohort of SLE patients. Methods A total of 118 SLE
      patients completed the SAGE. Providers completed the Systemic Lupus Erythematosus
      Disease Activity Index (SLEDAI) and the Systemic Lupus International
      Collaborative Clinics Damage Index (SLICC-DI). SAGE scores were grouped into
      normal (>16) and abnormal (<=16) categories. Univariate and multivariate analyses
      were performed. Results Of the 118 participants, 21(18%) scored <=16 on the SAGE
      instrument. In univariate analysis, race, ethnicity, household income, and SLICC
      DI scores were associated with the SAGE ( p < 0.05). In multivariable analysis,
      abnormal SAGE score was independently associated with higher SLICC-DI score (odds
      ratio (OR) = 1.44, 95% confidence intervals 1.04-1.99, p = 0.03)), Hispanic
      ethnicity (OR = 43.4, 95% CI 3.1-601, p = 0.005), and lower household income (OR
      = 11.9 for <=$15,000 vs >$50,000, 95% CI 2.45-57, p = 0.002). Conclusions In SLE
      patients, this study demonstrates an independent relationship between
      neurocognitive impairment (as measured by the SAGE) and higher lupus-related
      damage, as measured by the SLICC-DI, and lower household income. Abnormal SAGE
      scores were also associated with Hispanic ethnicity. A language barrier could
      explain this because the SAGE instrument was conducted in English only. The SAGE
      was feasible to measure in the clinic setting.

PMID- 29466915
TI  - Effects of Sexual Media Literacy Education for School Nurses in South Korea.
AB  - This study aimed to examine the effects of a sexual education program (SEP)
      focused on sexual media literacy (SML) for school nurses. A quasi-experimental,
      pre-/posttest design was used to examine SML knowledge, awareness,
      reinterpretation skill, and self-efficacy. A total of 66 school nurses
      participated. The experimental group ( n = 35) participated in an 18-hr SEP that
      focused on SML, while the control group ( n = 31) did not. The experimental group
      showed significant improvement in knowledge ( t = 6.47, d = 1.62, p < .001),
      awareness ( t = 5.08, d = 1.19, p < .001), reinterpretation skill ( t = 4.81, d =
      2.28, p < .001), and self-efficacy ( t = 8.29, d = 1.38, p < .001) as compared to
      the control group. The SEP developed in this study may be an effective
      educational intervention for school nurses.

PMID- 29466914
TI  - Inducible CRISPR genome editing platform in naive human embryonic stem cells
      reveals JARID2 function in self-renewal.
AB  - To easily edit the genome of naive human embryonic stem cells (hESC), we
      introduced a dual cassette encoding an inducible Cas9 into the AAVS1 site of
      naive hESC (iCas9). The iCas9 line retained karyotypic stability, expression of
      pluripotency markers, differentiation potential, and stability in 5iLA and EPS
      pluripotency conditions. The iCas9 line induced efficient homology-directed
      repair (HDR) and non-homologous end joining (NHEJ) based mutations through CRISPR
      Cas9 system. We utilized the iCas9 line to study the epigenetic regulator, PRC2
      in early human pluripotency. The PRC2 requirement distinguishes between early
      pluripotency stages, however, what regulates PRC2 activity in these stages is not
      understood. We show reduced H3K27me3 and pluripotency markers in JARID2 2iL-I-F
      hESC mutants, indicating JARID2 requirement in maintenance of hESC 2iL-I-F state.
      These data suggest that JARID2 regulates PRC2 in 2iL-I-F state and the lack of
      PRC2 function in 5iLA state may be due to lack of sufficient JARID2 protein.

PMID- 29466916
TI  - Augmented migration of mesenchymal stem cells correlates with the subsidiary
      CXCR4 variant.
AB  - Use of mesenchymal stem cells (MSCs) has been introduced as a promising tool, for
      structural and functional recovery of damaged tissues/organs. Studies have
      indicated that interactions between chemokine receptors and their ligands have a
      critical role in homing of MSCs to the site of injury. Although CXCR4 variants
      have been characterized, the exact role of each transcript in homing has remained
      unclear. In this study, cells were pretreated with various hypoxia-mimicking
      compounds (valproic acid, cobalt-chloride, and deferoxamine mesylate). Results
      indicated that both variants of CXCR4 were overexpressed after 24 hours of
      treatments and their expression could cooperatively induce and promote the cell
      migration. Moreover, deferoxamine mesylate was more effective in overexpression
      of variant A (lo), which resulted in higher level of CXCR4 protein and the
      highest rate of migration of the cells. In conclusion, our findings may have
      important potential implications in clinical applications, reinforcing the
      concept that manipulating the expression of specific CXCR4 variants may increase
      migration of MSCs.

PMID- 29466917
TI  - Cure of chronic hepatitis C virus infection in an HIV-coinfected patient with
      multiple comorbidities and drug interaction challenges.
AB  - Curing hepatitis C virus (HCV) infection in patients harbouring multiple severe
      comorbidities is a medical challenge. Evidence-based data are lacking regarding
      HCV treatment with direct-acting antiviral regimens in particular populations of
      HCV/HIV-coinfected patients with cirrhosis and chronic kidney disease on
      haemodialysis. Here, we present the HCV treatment challenges facing a patient
      with HIV coinfection, prior failure of both HIV-1 and HCV therapy, cirrhosis, end
      stage renal failure on haemodialysis, as well as management of drug-drug
      interactions, especially given the need to receive long-term amiodarone therapy.

PMID- 29466918
TI  - Multiple sclerosis and HIV: a case of multiple sclerosis-immune reconstitution
      inflammatory syndrome associated with antiretroviral therapy initiation.
AB  - Studies have suggested that the incidence of multiple sclerosis (MS) in HIV
      infected (HIV+) patients is lower than that of the general population. Here, we
      present a case of MS in an HIV+ patient with a relatively suppressed CD4 cell
      count who developed clinical and radiographic disease worsening in the setting of
      antiretroviral therapy (ART) initiation. A 47-year-old HIV+ woman (CD4 cell count
      216 cells/ul) presented with decreased vision in her right eye. Magnetic
      resonance imaging (MRI) revealed optic nerve enhancement and open ring-enhancing
      lesions in the brain concerning for demyelinating disease. Cerebrospinal fluid
      was tested extensively for infection and malignancy with no abnormal findings.
      She received five days of intravenous methylprednisolone. Nine days later, she
      was restarted on ART. Three weeks later, she was readmitted with left eye vision
      loss and left hemiplegia (CD4 cell count 342 cells/ul). Repeat imaging showed
      multiple new enhancing lesions. Several cases have described severe MS relapses
      and unusually widespread demyelinating lesions on MRI after withdrawal of
      immunosuppressive drugs. We posit that the clinical and radiographic progression
      that occurred in our patient after initiation of ART represented an immune
      reconstitution response to ART. Caution may be warranted when initiating ART in
      HIV+ patients with suppressed CD4 cell count and active MS.

PMID- 29466919
TI  - What qualities in a potential HIV pre-exposure prophylaxis service are valued by
      black men who have sex with men in London? A qualitative acceptability study.
AB  - Black men who have sex with men (BMSM) have higher HIV incidence and prevalence
      when compared to other MSM, despite similar levels of condom use and testing. Pre
      exposure prophylaxis (PrEP) could be a useful intervention to reduce these
      inequalities. This research therefore aims to understand the dimensions of
      acceptability of a potential PrEP service for BMSM aged 18-45 years in London. In
      depth semi-structured interviews were conducted with 25 PrEP-eligible BMSM
      between April and August 2016. Interviews were recorded and transcribed verbatim,
      then subject to a thematic framework analysis, informed by intersectionality
      theory. BMSM had distinct preferences for sexual health services, which have
      implications for PrEP service development. Three primary domains emerged in our
      analysis: proximity and anonymity; quality, efficiency and reassurance; and
      understanding, empathy and identity. These relate, respectively, to preferences
      regarding clinic location and divisions from community, features of service
      delivery and staff characteristics. Due to concerns about confidentiality,
      community-based services may not be useful for this group. Careful consideration
      in regards to components used in service development will facilitate ongoing
      engagement. Interpersonal skills of staff are central to service acceptability,
      particularly when staff are perceived to be from similar cultural backgrounds as
      their patients.

PMID- 29466920
TI  - Trajectory of Functional Independent Measurements during First Five Years after
      Moderate and Severe Traumatic Brain Injury.
AB  - A better understanding of long-term functional recovery process for patients with
      traumatic brain injury (TBI) facilitates effective rehabilitations. The aim of
      this study was to classify and characterize patients with moderate-to-severe TBI
      based on their functional trajectories up to 5 years post-injury. The study
      included 121 patients with moderate-to-severe TBIs (International Classification
      of Diseases, Tenth Revision [ICD-10], S06.0-S06.9), 16-55 years of age, and
      admitted at Trauma Referral Hospital within 24 h of injury between 2005 and 2007.
      Demographics and injury characteristics were documented at the admission, and
      functional status was recorded at 3 months and 1 and 5 years post-injury using
      Functional Independence Measure motor (FIM-M) and cognitive (FIM-C) subscales. We
      used group-based trajectory models to classify patients' functional trajectories
      over a 5-year period. For FIM-M, three trajectories were identified: 8.2% of
      patients showed stable low recovery (13.6 +/- 1.5, 17.9 +/- 8.8, and 21.0 +/-
      17.9), 9.2% elevated good recovery (35.8 +/- 14.5, 75.5 +/- 12.4, and 85.5 +/-
      8.1), and 82.6% stable good recovery (89.0 +/- 3.6, 90.3 +/- 1.9, and 90.8 +/-
      1.0) at the three follow-up points, respectively. For FIM-C, four trajectories
      were revealed: 4.1% of patients showed stable low recovery (5.0 +/- 0, 5.0 +/- 0,
      and 5.0 +/- 0), 12.6% delayed moderate recovery (8.9 +/- 3.5, 20.6 +/- 4.6, and
      28.3 +/- 3.8), 28.7% elevated good recovery (27.0 +/- 3.8, 30.4 +/- 7.3, and 31.1
      +/- 2.3), and 54.6% stable good recovery (32.8 +/- 2.3, 34.6 +/- 1.0, and 34.7 +/
      1.0). The results suggest that three FIM-M and four FIM-C trajectories described
      various patterns of functional recovery 5 years after moderate-to-severe TBI,
      with stable good recovery being the most common trajectory. Identifying and
      characterizing the trajectory memberships should enable targeted rehabilitation
      programs, inform patient-centered care, and improve long-term outcomes.

PMID- 29466921
TI  - The confabulation battery: Instructions and international data from normal
      participants.
AB  - Confabulation is an unusual sign in neurological and in neuropsychological
      pathologies. In this article we present an objective neuropsychological
      instrument, the Confabulation Battery (CB), which allows the quantifying and
      qualifying of different types of confabulations. The CB was administered to
      French and Italian normal participants. Data from the present study will allow
      clinicians and researchers, using the CB, to know how much and in which memory
      domains their confabulating patients confabulate compared to normal participants.
      We present international data, instructions and guidelines for the CB, a tool
      used in different ways worldwide. Not quantifying confabulations, namely not
      reporting how much and in which domain patients confabulate, can hardly lead to
      conclusions on the neurocognitive bases of this phenomenon. Following the
      instructions in this article, versions of the CB can be adapted in different
      languages and cultures. Quantification and qualification of confabulation is
      necessary and demanded in order to compare sensibly data from different research
      and clinical groups.

PMID- 29466922
TI  - Rabbit Calvarial Defect Model for Customized 3D-Printed Bone Grafts.
AB  - Bone graft materials are commonly used to regenerate various bone defects, but
      their application is often limited because of the complex defect shape in various
      clinical conditions. Hence, customized bone grafts using three-dimensional (3D)
      printing techniques have been developed. However, conventional simple bone defect
      models are limited for evaluating the benefits and manufacturing accuracy of 3D
      printed customized bone grafts. Thus, the aim of the present study was to develop
      a complex-shaped bone defect model. We designed an 8-shaped bony defect that
      consists of two simple circles attached to the rabbit calvarium. To determine the
      critical-sized defect (CSD) of the 8-shaped defects, 5.6- and 7-mm-diameter
      trephine burs were tested, and the 7-mm-diameter bur could successfully create a
      CSD, which was easily reproducible on the rabbit calvarium. The rate of new bone
      formation was 28.65% +/- 8.63% at 16 weeks following creation of the defect. To
      confirm its efficacy for clinical use, the 8-shaped defect was created on a
      rabbit calvarium and 3D computed tomography (CT) was performed. A
      stereolithography file was produced using the CT data, and a 3D-printed
      polycaprolactone graft was fabricated. Using our 8-shaped defect model, we were
      able to modify the tolerances of the bone graft and calvarial defect to fabricate
      a more precise bone graft. Customized characteristics of the bone graft were then
      used to improve the accuracy of the bone graft. In addition, we confirmed the
      fitting ability of the 3D-printed graft during implantation of the graft. Our 8
      shaped defect model on the rabbit calvarium using a 7.0-mm trephine bur may be a
      useful CSD model for evaluating 3D-printed graft materials.

PMID- 29466923
TI  - Impact of a Standardized Beta-Lactam Allergy Questionnaire on Aztreonam Use.
AB  - METHODS: This quasi-experimental study compared the aztreonam utilization in
      patients with self-reported beta-lactam allergies admitted to an inpatient
      service between two study periods (pre- and post-implementation). Post
      implementation followed the initiation of a standardized beta-lactam allergy
      questionnaire, a student pharmacist-driven performance improvement project for
      beta-lactam allergy documentation. Interviews clarified the allergy, reaction
      history, and any previous tolerance of beta-lactams. If receiving aztreonam at
      the time of the questionnaire, recommendations were made for changes in therapy
      if deemed appropriate by the pharmacist. RESULTS: A total of 95 patients were
      included in the pre-implementation group versus 65 patients in the post
      implementation group. Baseline characteristics were similar. The average number
      of aztreonam doses per 1000 patient-days in the post-implementation group was
      decreased (21.23 vs 9.05, P = .003). The average number of days of therapy per
      1000 patient-days in the post-implementation group was decreased (8.79-4.24, P =
      .016). An increase in the number of aztreonam de-escalations was observed post
      implementation ( P = .003). A total of 122 questionnaires were completed with 114
      allergy documentation updates. There were no reported instances of adverse
      events. CONCLUSION: Utilization of a standardized beta-lactam allergy
      questionnaire as a pharmacy education tool resulted in a statistically
      significant decrease in aztreonam utilization, based on doses, days of therapy,
      and de-escalations.

PMID- 29466924
TI  - Ventriculoatrial synchrony induced heart failure.
AB  - OBJECTIVE AND IMPORTANCE: Endless loop tachycardia or pacemaker-mediated
      tachycardia, and atrioventricular desynchronization arrhythmia or repetitive non
      reentrant ventriculoatrial synchrony (RNRVAS) are two forms of reverse impulse
      conduction - ventriculoatrial (VA) synchrony. Although VA synchrony can
      theoretically cause aggravation of heart failure, clinical cases describing
      severe consequential heart failure are lacking. CLINICAL PRESENTATION AND
      INTERVENTION: We describe a case of a 60-year-old patient who underwent primary
      percutaneous coronary intervention and mitral valve surgery. Implantation of a
      two-chamber pacemaker was also performed during the same hospitalization due to
      development of third-degree atrioventricular block. Ten months later, he
      presented with a severe form of heart failure with a significant reduction of
      left ventricular ejection fraction (LVEF). The atrial lead was displaced and VA
      synchrony was registered (RNRVAS-like condition). The pacemaker was reprogrammed
      and VA synchrony induced heart failure was successfully resolved.
      Echocardiographic follow-up showed improvement in LVEF. CONCLUSION:
      Ventriculoatrial conduction can be present even when the patient has a complete
      atrioventricular block. Atrial lead displacement and consequently loss of atrial
      capture with preserved sensing can be a predisposing factor for initiation of
      ventriculoatrial synchrony. Permanent ventriculoatrial synchrony may provoke
      aggravation of heart failure.

PMID- 29466925
TI  - Peripheral VA-ECMO with direct biventricular decompression for refractory
      cardiogenic shock.
AB  - Cardiogenic shock and cardiac arrest are life-threatening emergencies that result
      in high mortality rates. Veno-arterial extracorporeal membrane oxygenation (VA
      ECMO) via peripheral cannulation is an option for patients who do not respond to
      conventional therapies. Left ventricular (LV) distention is a major limitation
      with peripheral VA-ECMO and is thought to contribute to poor recovery and the
      inability to wean off VA-ECMO. We report on a novel technique that combines
      peripheral VA-ECMO with off-pump insertion of a trans-apical LV venting cannula
      and a right ventricular decompression cannula.

PMID- 29466926
TI  - Pulling force prediction using neural networks.
AB  - PURPOSE: In ergonomics and human factors investigations, pulling force (PF)
      estimation has usually been achieved using various types of biomechanical models,
      and independent approximation of PF was done with the help of upper extremity
      joints. Recently, multiple regression methods have gained importance for task
      relevant inputs in predicting PF. Artificial neural networks (ANNs) also play a
      vital role in fitting the data; however, their use in work-related biomechanics
      and ergonomics is inadequate. Therefore, the current research aimed to accomplish
      comparative investigation of ANN and regression models by assessing their
      capacity to predict PF values. METHODS: Multipositional PF data were acquired
      from 200 subjects at three different handle heights and body locations. ANN and
      regression models were formed using a random sample of three subsets (75%
      training, 15% selection, 10% validation) for proving the outcomes. RESULTS: The
      comparison of ANN and regression models shows that the predictions of ANN models
      had a profoundly explained variance and lower root mean square difference values
      for the PF data at three handle heights. CONCLUSIONS: These outcomes advise that
      ANNs offer a precise and robust substitute for regression methods, and should be
      considered a useful method in biomechanics and ergonomics task assessments.

PMID- 29466927
TI  - "We own the illness": a qualitative study of networks in two communities with
      mixed ethnicity in Northern Norway.
AB  - BACKGROUND: When people in Northern Norway get ill, they often use traditional
      medicine. The global aim of this study was to examine the extended family
      networks' function and responsibility in cases of illness in the family, in two
      Northern Norwegian communities with a population of mixed ethnicity. METHODS:
      Semi-structured individual interviews with 13 participants and 4 focus group
      interviews with total 11 participants were conducted. The text data was
      transcribed verbatim and analysed based on the criteria for content analysis.
      RESULTS: The participants grew up in areas where it was common to seek help from
      traditional healers. They were organized in networks and shared responsibility
      for the patient and they provided practical help and support for the family.
      According to the networks, health-care personnel should make room for the entire
      network to visit the patient in severe and life-threatening situations.
      CONCLUSION: Traditional networks are an extra resource for people in these
      communities. The networks seem to be essential in handling and disseminating hope
      and manageability on an individual as well as a collective level. Health
      personnel working in communities with mixed ethnicity should have thorough
      knowledge of the mixed culture, including the importance of traditional network
      to the patients.

PMID- 29466928
TI  - Mapping patterns of change in emotion-focused psychotherapy: Implications for
      theory, research, practice, and training.
AB  - An important objective in humanistic-experiential psychotherapies and
      particularly emotion-focused psychotherapy (EFT) is to map patterns of change.
      Effective mapping of the processes and pathways of change requires that in
      session processes be linked to in-session resolutions, immediate post-session
      changes, intermediate outcome, final therapy outcome, and longer-term change.
      This is a challenging and long-term endeavour. Fine-grained descriptions of in
      session processes that lead to resolution of specific interpersonal and
      intrapersonal issues linked with longer-term outcomes are the foundation of EFT,
      the process-experiential approach. In this paper, evidence in support of EFT as a
      treatment approach will be reviewed along with research on two mechanisms of
      change, viewed as central to EFT, clients' emotional processing and the
      therapeutic relationship conditions. The implications for psychotherapy research
      are discussed. Given the methodological constraints, there is a need for more
      innovative methodologies and strategies to investigate specific psychotherapy
      processes within and across different approaches to map patterns and mechanisms
      of change to enhance theory, research, practice, and training.

PMID- 29466929
TI  - Histological Scoring Method to Assess Bone Healing in Critical Size Bone Defect
      Models.
AB  - Large bone defects are a major problem in trauma and orthopedic surgery. Tissue
      engineering based treatments have emerged as promising alternatives to
      traditional bone grafting techniques. Critical size bone defect animal models
      have been developed and widely used to evaluate and compare therapeutic
      effectiveness in bone tissue engineering treatments. To measure healing in a
      given defect after treatment, histological assessment methods are commonly used.
      These histological methods are typically qualitative and only measure the amount
      of newly formed bone. In this study, we introduce a new histological scoring
      method that in addition to new bone formation also measures newly formed
      "cartilage," "fibrous tissue," and "remnant bone defect size." Using Kappa
      analysis and interclass correlation analysis, we verified the reliability of our
      new scoring method. These additional parameters make it possible to differentiate
      between the hard callus and soft callus phases of healing and, thus, derive more
      valuable information about the effect different tissue-engineering treatments
      have on the healing process.

PMID- 29466930
TI  - Mechanism of MicroRNA-708 Targeting BAMBI in Cell Proliferation, Migration, and
      Apoptosis in Mice With Melanoma via the Wnt and TGF-beta Signaling Pathways.
AB  - OBJECTIVE: The aim of this study was to evaluate the mechanisms involved with
      miRNA-708 and its targeting of bone morphogenetic protein and activin membrane
      bound inhibitor in cell proliferation, migration, and apoptosis in mice with
      melanoma via the Wnt and transforming growth factor beta signaling pathways.
      METHODS: Sixty mice were recruited of which 40 were subsequently assigned into
      the experimental group (22 mice were successfully established as melanoma model
      and 18 mice used in tumor xenograft), and the normal control group consisted of
      20 mice. B16 cells were assigned to the normal, blank, and negative control, miR
      708 mimics, miR-708 inhibitors, si-BAMBI, and miR-708 inhibitors + si-bone
      morphogenetic protein and activin membrane-bound inhibitor groups. Western
      blotting and reverse transcription quantitative polymerase chain reaction were
      employed to detect the expression levels within the tissues and cell lines. TCF
      luciferase reporter (TOP-FLASH) or a control vector (FOP-FLASH) was applied to
      detect the activity of the Wnt signaling pathway. MTT3-(4,5-Dimethylthiazol-2-yl)
      2,5 diphenyltetrazolium bromide assay, flow cytometry, scratch test, and
      Transwell assay were conducted, respectively, for cell proliferation, apoptosis,
      migration, and invasion, while tumor xenograft procedures were performed on the
      nude mice recruited for the study. RESULTS: Compared to the normal control group,
      the model group displayed increased expressions of bone morphogenetic protein and
      activin membrane-bound inhibitor, Wnt10B, P53, and Bcl-2; TOPflash activity; beta
      catenin expression; cell proliferation; migration; and invasion capabilities
      while decreased expressions of miR-708, vascular endothelial growth factor, Fas,
      Bax, Caspase-3, and cleaved Caspase-3 and apoptosis rate. Compared to the blank
      and negative control groups, the miR-708 mimics and small-interfering RNA-bone
      morphogenetic protein and activin membrane-bound inhibitor groups exhibited
      decreases expressions of bone morphogenetic protein and activin membrane-bound
      inhibitor, Wnt10B, P53, and Bcl-2 and decreased proliferation, migration, and
      invasion capabilities, while increases in the apoptosis rate, expressions of
      vascular endothelial growth factor, Fas, Bax, Caspase-3, and cleaved Caspase-3;
      however, downregulated levels of TOPflash activity and beta-catenin expression
      were recorded. The miR-708 inhibitors group displayed an opposite trend.
      CONCLUSION: Downregulation of miR-708-targeted bone morphogenetic protein and
      activin membrane-bound inhibitor inhibits the proliferation and migration of
      melanoma cells through the activation of the transforming growth factor beta
      pathway and the suppression of Wnt pathway.

PMID- 29466931
TI  - Comparative in vitro activity of ceftaroline and comparator agents against
      nosocomial Gram-negative and Gram-positive clinically significant bacterial
      isolates from patients in a teaching hospital in Kuwait.
AB  - The objective was to test the in vitro activities of ceftaroline and comparator
      agents against clinical isolates of Gram-negative and Gram-positive bacteria.
      Isolates were identified with VITEK II. Susceptibility testing was with E test. A
      total of 1264 isolates were tested. Compared to other cephalosporins, ceftaroline
      demonstrated excellent in vitro activities (MIC90, <=0.5 mg/L) against
      Escherichia coli, Salmonella spp. and Haemophilus influenzae. When matched with
      the comparator cephalosporins, ceftaroline demonstrated the greatest activity
      against methicillin-susceptible Staphylococcus aureus (MSSA), with MIC90 of 0.25
      mg/L. Ceftaroline's MIC90s against both community-associated methicillin
      resistant S. aureus (MRSA) and hospital-acquired MRSA were 0.5 and 1 mg/L,
      respectively. Major discrepancies were noted between E test and disc diffusion
      tests for ceftaroline only against 16 Gram-negative and 16 Gram-positive
      isolates. Ceftaroline demonstrated an excellent in vitro activity against the
      majority of clinically significant Gram-negative and Gram-positive isolates
      obtained from proven cases of bacterial infections.

PMID- 29466932
TI  - A Single Radioactive Iodine Treatment Has a Deleterious Effect on Ovarian Reserve
      in Women with Thyroid Cancer: Results of a Prospective Pilot Study.
AB  - BACKGROUND: Women of reproductive age with differentiated thyroid cancer (DTC)
      often need radioactive iodine (RAI) treatment after surgery. In contrast to the
      well-documented effect of RAI on testicular function, the potential negative
      effects of this treatment on ovarian reserve have been largely dismissed. The
      objective of this pilot study was to examine the possibility that RAI treatment
      is deleterious to the ovarian reserve by prospectively measuring the
      concentration of anti-Mullerian hormone (AMH) after RAI treatment. METHODS:
      Thirty premenopausal women (Mage = 34 years; range 20-45 years) with a new
      diagnosis of DTC scheduled to undergo RAI ablation were recruited for this study.
      All of them had TNM stage 1 disease (T1-3, N0, or N1, M0), and were scheduled to
      receive RAI activities ranging from 30 to 150 mCi. AMH was measured at baseline
      and at 3, 6, 9, and 12 months after the administration of RAI. RESULTS: Of the 30
      women, only 24 returned after the baseline assessment. RAI treatment resulted in
      a significant decrease in AMH concentrations at three months, from 3.25 +/- 2.75
      to 1.9 +/- 1.74 ng/mL (p < 0.0001). Only partial recovery was subsequently
      documented. Eighty-two percent of subjects had final values below baseline
      levels, such that at one year, serum AMH was still 32% lower than prior to
      treatment (2.36 +/- 1.88 ng/mL; p < 0.005). The only two continuous variables
      that correlated with the extent of AMH reduction at three months were the woman's
      age (r = 0.51; p = 0.02) and the age at menarche (r = 0.48; p = 0.03).
      Importantly, the RAI dose was not associated with the extent of AMH reduction and
      neither were smoking or the use of birth control pills. Older subjects (>=35
      years) were significantly more likely to experience a marked AMH reduction at
      three months (63.7 +/- 18.5% vs. 33.1 +/- 29.2%; p = 0.01). The only predictor of
      recovery after one year was the extent of AMH decrease at three months: the lower
      the decline, the higher the chances for recovery. CONCLUSIONS: RAI in DTC has a
      rapid and profound effect on ovarian reserve, with only a partial recovery
      potential. In an era of declining human fertility, it is of relevance to
      recognize the potentially adverse effect of RAI in women of reproductive age. AMH
      measurement may be useful as a tool in this decision-making process.

PMID- 29466933
TI  - Efficiency of Nannochloropsis oculata and Bacillus polymyxa symbiotic composite
      at ammonium and phosphate removal from synthetic wastewater.
AB  - Many issues, such as, DO accumulation, N2 fixation obstacle, and carbon dioxide
      diffusion, hamper the application of microalgae-alginate immobilization in
      wastewater treatment. The objective of this study was to evaluate the effect of
      the microalgae Nannochloropsis oculata immobilized with the bacterium Bacillus
      polymyxa in alginate on ammonium and phosphate removal from synthetic wastewater.
      Results show that the co-immobilized Bacillus-Nannochloropsis can exploit
      ammonium and phosphate from wastewater more effectively than the immobilized
      Nannochloropsis, and immobilized Bacillus alone. A significantly higher ammonium
      and phosphate removal efficiency was found in co-immobilized Bacillus
      Nannochloropsis (59.85%, 90.44%) than of that in immobilized Nannochloropsis
      (49.56%, 77.36%), and Bacillus immobilized (31.46%, 29.66%) alone. Additionally,
      the most effective co-immobilization mixture ratio for wastewater treatment was
      found to contain equal suspension (108 cell/ml) volume of the Nannochloropsis and
      Bacillus. Nannochloris and Bacillus can coexist harmoniously with the symbiotic
      and synergistic relationship, and the Nannochloropsis oculata- Bacillus polymyxa
      combination can be useful as a potential method to develop novel wastewater
      treatment.

PMID- 29466934
TI  - Thirty-six-month outcomes of drug-eluting balloon angioplasty in the
      infrapopliteal arteries.
AB  - Objectives To evaluate 36-month outcomes of drug-eluting balloons in
      infrapopliteal (=below-the-knee) arterial segments, we made a prospective
      registry enrolling patients (Rutherford class 2 to 5, ankle-brachial index 0.4
      0.7) who were revascularized with drug-eluting balloon from August 2011 to
      December 2014. Methods Three hundred and seven infrapopliteal arteries were
      revascularized only with drug-eluting balloon. Endpoints included target lesion
      revascularization, primary patency rate, and changes in ankle-brachial index and
      Rutherford class. Results Both ankle-brachial index improvement and Rutherford
      reduction were statistically significant (p < 0.001). At 36 months control, ankle
      brachial index improvement was 59.3% (p = 0.032). The clinically driven target
      lesion revascularization rate was 28% at 36 months. Limb salvage was accomplished
      in 73.6% of the critical limb ischemia cases, and complete wound healing was
      detected in 67.8% of cases with Rutherford category 5. Overall, the 1-year
      primary patency rate was 32.5%. Conclusions Drug-eluting balloons have shown
      successful performance in infrapopliteal arteries in mid-term, and evidence
      regarding clinical effectiveness and safety supports drug-eluting balloon
      angioplasty as the first line therapy in this segment.

PMID- 29466935
TI  - Endovascular approach in isolated abdominal aortic dissections.
AB  - Background Here, we report the mid-term results of endovascular treatment of
      isolated dissection of the abdominal aorta, which is a very rare pathology.
      Materials and methods A total of 11 patients (4 males (36.3%) and 7 females
      (63.6%)) aged 42-72 (mean, 60.3 +/- 10.45) years with isolated dissection of the
      abdominal aorta underwent endovascular stent-graft treatment at our institution
      between August 2010 and September 2015. Eight patients were symptomatic, and the
      remaining three were asymptomatic. The asymptomatic patients had aortic aneurysms
      coexisting with dissection. Eight patients without aneurysm had spontaneous
      dissections, and the most common symptom was unresponsive abdominal pain. Results
      The mean abdominal aorta diameter was 46.7 +/- 20.6 (range, 31.2-100.9) mm and
      the mean dissection length was 71.1 +/- 47.3 (range, 17-162) mm. Aorto-bi-iliac
      stent grafts were used in all patients, and were placed successfully under spinal
      anesthesia in all but one (90.9%) patient. Occlusion developed in one patient due
      to compression of the aorto-bi-iliac graft. Right-left femoral-femoral bypass was
      performed in this patient, who could not be placed on the opposite side. In
      addition, the graft was placed in one patient using the left renal artery chimney
      technique. No intraoperative mortality occurred, and open surgery was not
      required. In addition, no death occurred and no additional intervention was
      required during the mean follow-up period of 25.5 +/- 17.1 (range, 6-60) months.
      Conclusion Limited data regarding endovascular treatment of isolated dissection
      of the abdominal aorta are available in the literature. Based on data obtained in
      a limited number of patients, we consider endovascular aortic repair to be a good
      alternative to surgery due to its low morbidity and mortality rates.

PMID- 29466936
TI  - Utilization and in-hospital outcomes associated with atherectomy in the treatment
      of peripheral vascular disease: An observational analysis from the National
      Inpatient Sample.
AB  - Objective Percutaneous revascularization for patients with peripheral arterial
      disease has become a treatment of choice for many symptomatic patients. The
      presence of severe arterial calcification presents many challenges for successful
      revascularization. Atherectomy is an adjunctive treatment option for patients
      with severe calcification undergoing percutaneous intervention. We sought to
      analyze the impact of atherectomy on in-hospital outcomes, length of stay, and
      cost in the percutaneous treatment of peripheral arterial disease. Methods
      Patients with lower extremity peripheral arterial disease undergoing percutaneous
      revascularization were assessed, utilizing the National Inpatient Sample (2012
      2014) and appropriate International Classification of Diseases, 9th Revision,
      Clinical Modification diagnostic and procedural codes. Patients who were not
      treated with atherectomy ( n = 51,037) were compared to those treated with
      atherectomy ( n = 11,408). Propensity score-matched analysis was performed to
      address baseline differences. Results After performing propensity score-matched
      analysis, 11,037 patients were included in each group. Utilization of atherectomy
      was associated with lower in-hospital mortality (2% vs. 1.4% p = 0.0006). All
      secondary outcomes were lower when using atherectomy except acute renal failure.
      Length of stay was slightly lower when using atherectomy (7.2 vs. 7.0 days, p =
      0.0494). However, median cost was higher in patients treated with atherectomy
      ($21,589 vs. $24,060, p = <0.0001). Conclusion The use of atherectomy was
      associated with significantly decreased in-hospital mortality, adverse events,
      and length of stay. Though, cost associated with atherectomy use is increased,
      this is offset by decreased in-hospital adverse outcomes. Appropriate use of
      atherectomy devices is an important tool in revascularization of peripheral
      arterial disease in select patients.

PMID- 29466937
TI  - Hybrid approach with endovascular and open surgical techniques for challenging
      aneurysms.
AB  - This study is a case series describing the management of complex aneurysmal
      disease using the principles of both open and endovascular techniques.

PMID- 29466938
TI  - Application of Nanotechnology for waste management: Challenges and limitations.

PMID- 29466939
TI  - Interatrial block and atrial remodeling assessed using speckle tracking
      echocardiography.
AB  - BACKGROUND: To evaluate the possibility of left atrial (LA) remodeling using
      speckle tracking echocardiography (STE) in patients with interatrial block (IAB).
      METHODS: We performed a cross-sectional study with three groups of patients: 56
      without IAB, 21 with partial IAB (pIAB), and 22 with advanced IAB (aIAB).
      Transthoracic echocardiographic (TTE) STE was performed and clinical and
      echocardiographic findings were analyzed. RESULTS: TTE showed higher LA
      volume/body surface area in the patients with IAB. With STE, the absolute value
      of strain rate during atrial booster pump function (SRa) and early reservoir
      period (SRs) decreased in the pIAB group and even more in the aIAB group,
      compared to the group without IAB. The independent variables were the
      echocardiographic measures of LA size and function. After adjusting for
      confounders, both multiple linear regression and multivariate multinomial
      regression showed good correlation with dependent variables: longer P-wave
      duration on electrocardiography and with the type of IAB, respectively. SRa (p <
      0.001), SRs (p < 0.001), and maximal peak LA longitudinal strain in the reservoir
      period (p = 0.009) were independently associated with P-wave duration. SRa was
      also associated with the presence of pIAB (OR = 11.5; 95% confidence interval
      (CI): 2.7-49.0; p = 0.001) and aIAB, (OR = 98.2; 95% CI: 16-120.4; p < 0.001) and
      SRs was associated with pIAB (OR: 0.03; CI: 0.003-0.29; p = 0.003) and with aIAB
      (OR: 0.008; CI: 0.001-0.12; p = 0.004). CONCLUSIONS: IAB correlates directly with
      structural remodeling and a decrease in the absolute value of LA SRa and SRs
      determined using STE.

PMID- 29466940
TI  - Analytical parameters and validation of homopolymer detection in a pyrosequencing
      based next generation sequencing system.
AB  - BACKGROUND: Current technologies in next-generation sequencing are offering high
      throughput reads at low costs, but still suffer from various sequencing errors.
      Although pyro- and ion semiconductor sequencing both have the advantage of
      delivering long and high quality reads, problems might occur when sequencing
      homopolymer-containing regions, since the repeating identical bases are going to
      incorporate during the same synthesis cycle, which leads to uncertainty in base
      calling. The aim of this study was to evaluate the analytical performance of a
      pyrosequencing-based next-generation sequencing system in detecting homopolymer
      sequences using homopolymer-preintegrated plasmid constructs and human DNA
      samples originating from patients with cystic fibrosis. RESULTS: In the plasmid
      system average correct genotyping was 95.8% in 4-mers, 87.4% in 5-mers and 72.1%
      in 6-mers. Despite the experienced low genotyping accuracy in 5- and 6-mers, it
      was possible to generate amplicons with more than a 90% adequate detection rate
      in every homopolymer tract. When homopolymers in the CFTR gene were sequenced
      average accuracy was 89.3%, but varied in a wide range (52.2 - 99.1%). In all but
      one case, an optimal amplicon-sequencing primer combination could be identified.
      In that single case (7A tract in exon 14 (c.2046_2052)), none of the tested
      primer sets produced the required analytical performance. CONCLUSIONS: Our
      results show that pyrosequencing is the most reliable in case of 4-mers and as
      homopolymer length gradually increases, accuracy deteriorates. With careful
      primer selection, the NGS system was able to correctly genotype all but one of
      the homopolymers in the CFTR gene. In conclusion, we configured a plasmid test
      system that can be used to assess genotyping accuracy of NGS devices and
      developed an accurate NGS assay for the molecular diagnosis of CF using self
      designed primers for amplification and sequencing.

PMID- 29466941
TI  - Transcription start site profiling uncovers divergent transcription and enhancer
      associated RNAs in Drosophila melanogaster.
AB  - BACKGROUND: High-resolution transcription start site (TSS) mapping in D.
      melanogaster embryos and cell lines has revealed a rich and detailed landscape of
      both cis- and trans-regulatory elements and factors. However, TSS profiling has
      not been investigated in an orthogonal in vivo setting. Here, we present a
      comprehensive dataset that links TSS dynamics with nucleosome occupancy and gene
      expression in the wandering third instar larva, a developmental stage
      characterized by large-scale shifts in transcriptional programs in preparation
      for metamorphosis. RESULTS: The data recapitulate major regulatory classes of
      TSSs, based on peak width, promoter-proximal polymerase pausing, and cis
      regulatory element density. We confirm the paucity of divergent transcription
      units in D. melanogaster, but also identify notable exceptions. Furthermore, we
      identify thousands of novel initiation events occurring at unannotated TSSs that
      can be classified into functional categories by their local density of histone
      modifications. Interestingly, a sub-class of these unannotated TSSs overlaps with
      functionally validated enhancer elements, consistent with a regulatory role for
      "enhancer RNAs" (eRNAs) in defining developmental transcription programs.
      CONCLUSIONS: High-depth TSS mapping is a powerful strategy for identifying and
      characterizing low-abundance and/or low-stability RNAs. Global analysis of
      transcription initiation patterns in a developing organism reveals a vast number
      of novel initiation events that identify potential eRNAs as well as other non
      coding transcripts critical for animal development.

PMID- 29466942
TI  - Identification of novel genes in the carotenogenic and oleaginous yeast
      Rhodotorula toruloides through genome-wide insertional mutagenesis.
AB  - BACKGROUND: Rhodotorula toruloides is an outstanding producer of lipids and
      carotenoids. Currently, information on the key metabolic pathways and their
      molecular basis of regulation remains scarce, severely limiting efforts to
      engineer it as an industrial host. RESULTS: We have adapted Agrobacterium
      tumefaciens-mediated transformation (ATMT) as a gene-tagging tool for the
      identification of novel genes in R. toruloides. Multiple factors affecting
      transformation efficiency in several species in the Pucciniomycotina subphylum
      were optimized. The Agrobacterium transfer DNA (T-DNA) showed predominantly
      single-copy chromosomal integrations in R. toruloides, which were trackable by
      high efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR). To demonstrate
      the application of random T-DNA insertions for strain improvement and gene
      hunting, 3 T-DNA insertional libraries were screened against cerulenin, nile red
      and tetrazolium violet respectively, resulting in the identification of 22
      mutants with obvious phenotypes in fatty acid or lipid metabolism. Similarly, 5
      carotenoid biosynthetic mutants were obtained through visual screening of the
      transformants. To further validate the gene tagging strategy, one of the
      carotenoid production mutants, RAM5, was analyzed in detail. The mutant had a T
      DNA inserted at the putative phytoene desaturase gene CAR1. Deletion of CAR1 by
      homologous recombination led to a phenotype similar to RAM5 and it could be
      genetically complemented by re-introduction of the wild-type CAR1 genome
      sequence. CONCLUSIONS: T-DNA insertional mutagenesis is an efficient forward
      genetic tool for gene discovery in R. toruloides and related oleaginous yeast
      species. It is also valuable for metabolic engineering in these hosts. Further
      analysis of the 27 mutants identified in this study should augment our knowledge
      of the lipid and carotenoid biosynthesis, which may be exploited for oil and
      isoprenoid metabolic engineering.

PMID- 29466943
TI  - Correction to: Jasmonate-mediated defence responses, unlike salicylate-mediated
      responses, are involved in the recovery of grapevine from bois noir disease.
AB  - CORRECTION: Following publication of the original article [1], it came to the
      attention of the authors that they had omitted to acknowledge the University of
      Parma. The Acknowledgement section should read as follows: "The authors kindly
      acknowledge the University of Parma (Department of Chemistry, Life Sciences and
      Environmental Sustainability; formerly Department of Life Sciences/Evolutionary
      and Functional Biology) for the transfer of funds obtained from the Ager project:
      GIALLUMI DELLA VITE: TECNOLOGIE INNOVATIVE PER LA DIAGNOSI E LO STUDIO DELLE
      INTERAZIONI PIANTA/PATOGENO, BANDO AGER VITICOLTURA DA VINO".

PMID- 29466944
TI  - Risk variants of the alpha-synuclein locus and REM sleep behavior disorder in
      Parkinson's disease: a genetic association study.
AB  - BACKGROUND: Parkinson's disease is a heterogeneous disorder where genetic factors
      may underlie clinical variability. Rapid eye movement sleep behavior disorder
      (RBD) is a parasomnia strongly linked to synucleinopathies, including Parkinson's
      disease. We hypothesized that SNCA variants conferring risk of Parkinson's
      disease would also predispose to an RBD phenotype. METHODS: We assessed possible
      RBD (pRBD) status using the RBD screening questionnaire and investigated known
      susceptibility variants for Parkinson's disease located in the alpha-synuclein
      (SNCA) and tau (MAPT) gene loci in 325 Parkinson's disease patients. Associations
      between genetic risk variants and RBD were investigated by logistic regression,
      and an independent dataset of 382 patients from the Parkinson's Progression
      Marker Initiative (PPMI) study was used for replication. RESULTS: pRBD was
      associated with rs3756063 located in the 5' region of SNCA (two-sided p = 0.018,
      odds ratio 1.44). We replicated this finding in the PPMI dataset (one-sided p =
      0.036, odds ratio 1.35) and meta-analyzed the results (two-sided p = 0.0032, odds
      ratio 1.40). The Parkinson's disease risk variant in the 3' region of SNCA and
      the MAPT variant showed no association with pRBD. CONCLUSIONS: Our findings
      provide proof of principle that a largely stable, dichotomous clinical feature of
      Parkinson's disease can be linked to a specific genetic susceptibility profile.
      Indirectly, it also supports the hypothesis of RBD as relevant marker for a
      distinct subtype of the disorder.

PMID- 29466945
TI  - Diversity and evolution of the repetitive genomic content in Cannabis sativa.
AB  - BACKGROUND: The repetitive content of the genome, once considered to be "junk
      DNA", is in fact an essential component of genomic architecture and evolution. In
      this study, we used the genomes of three varieties of Cannabis sativa, three
      varieties of Humulus lupulus and one genotype of Morus notabilis to explore their
      repetitive content using a graph-based clustering method, designed to explore and
      compare repeat content in genomes that have not been fully assembled. RESULTS:
      The repetitive content in the C. sativa genome is mainly composed of the
      retrotransposons LTR/Copia and LTR/Gypsy (14% and 14.8%, respectively), ribosomal
      DNA (2%), and low-complexity sequences (29%). We observed a recent copy number
      expansion in some transposable element families. Simple repeats and low
      complexity regions of the genome show higher intra and inter species variation.
      CONCLUSIONS: As with other sequenced genomes, the repetitive content of C.
      sativa's genome exhibits a wide range of evolutionary patterns. Some repeat types
      have patterns of diversity consistent with expansions followed by losses in copy
      number, while others may have expanded more slowly and reached a steady state.
      Still, other repetitive sequences, particularly ribosomal DNA (rDNA), show signs
      of concerted evolution playing a major role in homogenizing sequence variation.

PMID- 29466946
TI  - Performance of loop-mediated isothermal amplification assay in the diagnosis of
      pulmonary tuberculosis in a high prevalence TB/HIV rural setting in Uganda.
AB  - BACKGROUND: Smear microscopy lacks sensitivity especially in HIV co-infection,
      resulting in undiagnosed tuberculosis (TB) and high mortality. The loop-mediated
      isothermal amplification (TB-LAMP) assay can be staged with minimal
      infrastructure, is rapid, low cost and detection can be with the naked eye. We
      assessed feasibility and performance of Eiken TB-LAMP test at point-of-need in TB
      diagnosis in a high prevalence TB/HIV rural setting in Uganda. METHODS: From
      October 2013-February 2014, TB-LAMP testing was performed on sputum specimens
      from outpatient presumptive TB adults at a district hospital and two low-level
      health centers in Kiboga District where smear microscopy is the available routine
      diagnostic option. TB-LAMP was performed by a technician after a week of training
      in the district hospital. The technician had no prior experience in the
      technology. Samples from the low-level health centers were transported to the
      district hospital for TB-LAMP. RESULTS: Of the 233 presumptive TB (126 at
      hospital); 113 (48.5%) were HIV-infected; 129 (55%) male; median age 40 (IQR 30
      53). Compared to MTB culture, overall sensitivity and specificity of TB-LAMP were
      55.4% (95 CI 44.1-66.3) and 98.0% (95 CI 94.3-99.6) respectively. Among HIV
      infected participants, TB-LAMP sensitivity and specificity were 52.3% (95 CI 36.7
      67.5%) and 97.1% (95 CI 89.9-99.6) respectively; and 24.4% (95% CI 12.9-39.5) and
      98.6% (95% CI 95.1-99.8) respectively among smear-negatives. TB-LAMP sensitivity
      and specificity were 62.2% (95% CI 44.8-77.5) and 97.8% (95% CI 92.1-99.7) in the
      hospital setting where central testing occurred compared to 50.0% (95% CI 34.9
      65.1) and 98.4% (95% CI 91.2-100) respectively in low-level health centers where
      specimens were transported centrally. CONCLUSIONS: In this high prevalence TB/HIV
      rural setting, TB-LAMP performs better than conventional smear microscopy in
      diagnosis of MTB among presumptive TB patients although the sensitivity is lower
      than that reported by the World Health Organization. TB-LAMP can easily be
      performed following a short training period and in absence of sophisticated
      infrastructure and expertise.

PMID- 29466947
TI  - Stroke as an atypical initial presentation of giant cell arteritis.
AB  - BACKGROUND: Giant cell arteritis (GCA) is an immune mediated inflammatory disease
      of medium and large arteries which afflicts older people. The classical
      presentation features include: headache, visual disturbances, and jaw
      claudication. Patients diagnosed with GCA have also been observed to be at higher
      risk for the subsequent development of strokes. CASE PRESENTATION: We describe a
      case of an 84-year old right-handed man who presented to hospital with
      dysarthria, dysphagia, right-sided facial drop, a history of generalized weakness
      and multiple falls. He was admitted to geriatric medicine with the working
      diagnosis of a posterior circulation stroke syndrome. He was also started on
      antibiotic treatment for a possible community-acquired pneumonia because of the
      presence of a low-grade fever and a chest radiograph showing ill-defined left
      lower lobe airspace disease. Initial lab results were remarkable for an
      erythrocyte sedimentation rate (ESR) of 112 mm/h and a C-reactive protein (CRP)
      level of 110 mg/L consistent with an active inflammatory state. Neurovascular
      imaging showed mild atherosclerotic changes of the aortic arch and proximal great
      vessels without significant stenosis. The patient was started on daily high-dose
      prednisone because of the possibility of a cerebral vasculitis. Bilateral biopsy
      of temporal arteries showed giant cell arteritis. The patient's neurologic status
      and inflammatory markers significantly improved (ESR 52 mm/h, CRP 7.0 mg/L) and
      he was eventually discharged to a seniors home with services. CONCLUSION: The
      initial presentation of giant cell arteritis as a stroke syndrome, especially in
      the posterior circulation territory, is exceedingly rare. Other atypical
      presenting symptoms may include chronic cough and fever of unknown origin. The
      elevated ESR and CRP levels were clues to the diagnosis and clinical decision
      making should be driven by a high index of suspicion since no single test (ESR,
      CRP, temporal artery biopsy) has perfect sensitivity. Elevated CRP may have a
      role in increasing stroke risk. This case report illustrates that in older people
      clinicians must consider atypical presentations of disease more often since
      timely diagnosis and initiation of treatment can result in optimal outcomes.

PMID- 29466948
TI  - High inter-observer agreement of observer-perceived pain assessment in the
      emergency department.
AB  - BACKGROUND: Triage is used to prioritize the patients in the emergency
      department. The majority of the triage systems include the patients' pain score
      to assess their level of acuity by using a combination of patient reported pain
      and observer-perceived pain; the latter therefore requires a certain degree of
      inter-observer agreement. The aim of the present study was to assess the inter
      observer agreement of perceived pain among emergency department nurses and to
      evaluate if it was influenced by predetermined factors like age and gender.
      METHOD: A project assistant randomly recruited two nurses, who were not allowed
      to interact with each other, to assess patient pain intensity on the numeric
      ranking scale. The project assistant afterwards entered the pain scores in a
      predesigned electronic questionnaire. We used weighted Fleiss-Cohen (quadratic)
      kappa statistics, Bland-Altman statistics and logistic regression analysis to
      assess the inter-observer agreement. RESULTS: One hundred and sixty-two patients
      were included. They had a median age of 38 years and 45% were females. 30% of the
      patients were acute surgical patients and 70% acute orthopedic patients. The
      average time between the pain assessments were 1,7 min. The Bland Altman analysis
      found a mean difference in pain score of 0.2 and 95% limits of agreement of +/- 3
      point. When the NRS scores were translated to commonly used pain categories (no,
      mild, moderate or severe pain) we found a 70% agreement with a mean difference in
      categories of 0.05 and 95% limits of agreement of +/- 1 category. Patient age,
      gender, localization of pain, examination room or presence of a significant other
      did not affect the inter-observer agreement. CONCLUSION: We found 70% agreement
      on pain category between the nurses and it is justified that nurse-perceived pain
      assessment is used for triage in the emergency department.

PMID- 29466949
TI  - The association between pre pregnancy body mass index and risk of preeclampsia: a
      registry based study from Tanzania.
AB  - BACKGROUND: Preeclampsia is among the leading causes of maternal mortality and
      morbidity worldwide, occurs in 2-8% of all pregnancies, and is estimated to
      account for at least 9 % of maternal deaths in Africa. Studies from developed
      countries show that high pre pregnancy body mass index (BMI) increases the risk
      of preeclampsia. We examined the association between pre pregnancy BMI and the
      risk of preeclampsia in Tanzania, a low income country. METHODS: Data from the
      Kilimanjaro Christian Medical Center (KCMC) Medical Birth Registry recorded
      between July 2000 and May 2013 were used. We restricted the study population to
      singleton deliveries among women with no or one previous pregnancy. Pre pregnancy
      BMI (kg/m2) was categorized according to the WHO categories of underweight (less
      than 18.5), normal (18.5 - 24.9), overweight (25.0 - 29.9) and obese (30 or
      more). Potential confounders were adjusted for in multivariable analyses.
      RESULTS: Among the 17,738 singleton births, 6.6% of the mothers were underweight,
      62.1% were of normal BMI, 24.0% were overweight, and 7.3% were obese. Five
      hundred and eighty-two pregnancies (3.3%) were affected by preeclampsia. Compared
      to those with normal BMI, overweight and obese women had a higher risk of
      preeclampsia (aOR (95% CI) 1.4 (1.2 - 1.8) and 1.8 (1.3 - 2.4)), respectively,
      while underweight women had a lower risk (0.7 (0.4-1.1)). CONCLUSIONS: Pre
      pregnancy maternal overweight and obesity were associated with an increased risk
      of preeclampsia in Tanzania. Risks were similar to those reported in high income
      countries.

PMID- 29466950
TI  - HPV positive, wild type TP53, and p16 overexpression correlate with the absence
      of residual tumors after chemoradiotherapy in anal squamous cell carcinoma.
AB  - BACKGROUND: Anal residual tumors are consensually identified within six months of
      chemoradiotherapy and represent a persistent lesion that may have prognostic
      value for overall survival. The aim of this study was to evaluate the association
      of HPV and HIV status, p16 expression level and TP53 mutations with the absence
      of residual tumors (local response) in Squamous Cell Carcinoma (SCC) of the anal
      canal after chemoradiotherapy. METHODS: We performed a study on 78 patients with
      SCC of the anal canal who submitted to chemoradiotherapy and were followed for a
      six-month period to identify the absence or presence of residual tumors. HPV DNA
      was identified by polymerase chain reaction and direct sequencing, HIV RNA was
      detected by TaqMan amplification, p16 expression was detected by western
      blotting, and the mutational analysis of TP53 was performed by direct sequencing;
      additionally, samples carrying mutations underwent fluorescent in sit
      hybridization. The evaluation of the tumor response to treatment was conducted
      six months after the conclusion of chemoradiotherapy. The following
      classifications were used to evaluate the outcomes: a) no response (presence of
      residual tumor) and b) complete response (absence of residual tumor). RESULTS:
      The significant variables associated with the absence of residual tumors were HPV
      positive, p16 overexpressed, wild-type TP53, female gender, and stages I and II.
      Only the presence of HPV was independently correlated with the clinical response;
      this variable increased the chances of a response within six months by 31-fold.
      CONCLUSIONS: The presence of HPV in tumor cells was correlated with the absence
      of a residual tumor. This correlation is valuable and can direct future
      therapeutic approaches in the anal canal.

PMID- 29466952
TI  - Socio-economic, Knowledge Attitude Practices (KAP), household related and
      demographic based appearance of non-dengue infected individuals in high dengue
      risk areas of Kandy District, Sri Lanka.
AB  - BACKGROUND: Socio-economic, demographic factors and Knowledge Attitude Practices
      (KAPs) have been recognized as critical factors that influence the incidence and
      transmission of dengue epidemics. However, studies that characterize above
      features of a risk free or low risk population are rare. Therefore, the present
      study was conducted to characterize the household related, demographic, socio
      economic factors and KAPs status of five selected dengue free communities.
      METHOD: An analytical cross-sectional survey was conducted on selected
      demographic, socio-economic, household related and KAPs in five selected dengue
      free communities living in dengue risk areas within Kandy District, Central
      Province, Sri Lanka. Household heads of 1000 randomly selected houses were
      interviewed in this study. Chi-square test for independence, cluster analysis and
      Principal Coordinates (PCO) analysis were used for data analysis. RESULTS:
      Knowledge and awareness regarding dengue, (prevention of the vector breeding,
      bites of mosquitoes, disease symptoms and waste management) and attitudes of the
      community (towards home gardening, composting, waste management and maintenance
      of a clean and dengue free environment) are associated with the dengue free
      status of the study populations. CONCLUSIONS: The vector controlling authorities
      should focus on socio-economic, demographic and KAPs in stimulating the community
      to cooperate in the integrated vector management strategies to improve vector
      control and reduce transmission of dengue within Kandy District.

PMID- 29466951
TI  - A methodology review on the incremental prognostic value of computed tomography
      biomarkers in addition to Framingham risk score in predicting cardiovascular
      disease: the use of association, discrimination and reclassification.
AB  - BACKGROUND: Computed tomography (CT) biomarkers claim to improve cardiovascular
      risk stratification. This review focuses on significant differences in
      incremental measures between adequate and inadequate reporting practise. METHODS:
      Studies included were those that used Framingham Risk Score as a baseline and
      described the incremental value of adding calcium score or CT coronary angiogram
      in predicting cardiovascular risk. Searches of MEDLINE, EMBASE, Web of Science
      and Cochrane Central were performed with no language restriction. RESULTS: Thirty
      five studies consisting of 206,663 patients (men = 118,114, 55.1%) were included.
      The baseline Framingham Risk Score included the 1998, 2002 and 2008 iterations.
      Selective reporting, inconsistent reference groupings and thresholds were found.
      Twelve studies (34.3%) had major and 23 (65.7%) had minor alterations and the
      respective Delta AUC were significantly different (p = 0.015). When the baseline
      model performed well, the Delta AUC was relatively lower with the addition of a
      CT biomarker (Spearman coefficient = - 0.46, p < 0.0001; n = 33; 76 pairs of
      data). Other factors that influenced AUC performance included exploration of data
      analysis, calibration, validation, multivariable and AUC documentation (all p <
      0.05). Most studies (68.7%) that reported categorical NRI (n = 16; 46 pairs of
      data) subjectively drew strong conclusions along with other poor reporting
      practices. However, no significant difference in values of NRI was found between
      adequate and inadequate reporting. CONCLUSIONS: The widespread practice of poor
      reporting particularly association, discrimination, reclassification, calibration
      and validation undermines the claimed incremental value of CT biomarkers over the
      Framingham Risk Score alone. Inadequate reporting of discrimination inflates
      effect estimate, however, that is not necessarily the case for reclassification.

PMID- 29466953
TI  - The association between community-associated Staphylococcus aureus colonization
      and disease: a meta-analysis.
AB  - BACKGROUND: Colonization with Staphylococcus aureus is a well-defined risk factor
      for disease in hospitals, which can range from minor skin infections to severe,
      systemic diseases. However, the generalizability of this finding has not been
      thoroughly investigated outside of the hospital environment. We aimed to assess
      the role of S. aureus colonization as a risk factor for disease in the community.
      METHODS: We performed a meta-analysis of observational studies and searched
      PubMed for articles published between December 1979 and May 23, 2016. We included
      cohort, cross-sectional, and case-control studies that reported quantitative
      estimates of both S. aureus colonization and disease statuses of all study
      subjects. We excluded studies on recently hospitalized subjects, long-term care
      facilities, surgery patients, dialysis patients, hospital staff, S. aureus
      outbreaks, and livestock-associated infections. Our meta-analysis was performed
      using random-effects analysis to obtain pooled odds ratios (ORs) to compare the
      odds of S. aureus disease with respect to S. aureus colonization status. RESULTS:
      We identified 3477 citations, of which 12 articles on 6998 subjects met the
      eligibility criteria. Overall, subjects colonized with S. aureus were more likely
      to progress to disease than those who were non-colonized: (OR 1.87, 95% CI 1.21
      2.88, n = 7 studies). We observed a larger effect with methicillin-resistant S.
      aureus colonization (7.06, 4.60-10.84, n = 7 studies). However, the methicillin
      sensitive S. aureus colonization was not associated with greater odds of disease
      (1.20, 0.69-2.06, n = 4 studies). Heterogeneity was present across studies in all
      of the subgroups: S. aureus (I2 = 95.0%, chi2 = 120.3, p < 0.001), MRSA (I2 =
      92.8%, chi2 = 82.8, p = p < 0.001), and MSSA (I2 = 86.3%, chi2 = 21.8, p <
      0.001). CONCLUSIONS: While the majority of papers individually support the
      assumption that colonization is a risk factor for S. aureus disease in the
      general population, there is marked heterogeneity between studies and further
      investigation is needed to identify the major sources of this variance. There is
      a shortage of literature addressing this topic in the community setting and a
      need for further research on colonization as a focus for disease prevention.

PMID- 29466954
TI  - Cognitive function and the agreement between self-reported and accelerometer
      accessed physical activity.
AB  - BACKGROUND: Numerous studies have reported weak or moderate correlations between
      self-reported and accelerometer-assessed physical activity. One explanation is
      that self-reported physical activity might be biased by demographic, cognitive or
      other factors. Cognitive function is one factor that could be associated with
      either overreporting or underreporting of daily physical activity. Difficulties
      in remembering past physical activities might result in recall bias. Thus, the
      current study examines whether the cognitive function is associated with
      differences between self-reported and accelerometer-assessed physical activity.
      METHODS: Cross-sectional data from the population-based Activity and Function in
      the Elderly in Ulm study (ActiFE) were used. A total of 1172 community-dwelling
      older adults (aged 65-90 years) wore a uniaxial accelerometer (activPAL unit) for
      a week. Additionally, self-reported physical activity was assessed using the LASA
      Physical Activity Questionnaire (LAPAQ). Cognitive function was measured with
      four items (immediate memory, delayed memory, recognition memory, and semantic
      fluency) from the Consortium to Establish a Registry for Alzheimer's Disease
      Total Score (CERAD-TS). RESULTS: Mean differences of self-reported and
      accelerometer-assessed physical activity (MPA) were associated with cognitive
      function in men (rs = -.12, p = .002) but not in women. Sex-stratified multiple
      linear regression analyses showed that MPA declined with high cognitive function
      in men (beta = -.13; p = .015). CONCLUSION: Results suggest that self-reported
      physical activity should be interpreted with caution in older populations, as
      cognitive function was one factor that explained the differences between
      objective and subjective physical activity measurements.

PMID- 29466955
TI  - The effects of prehabilitation versus usual care to reduce postoperative
      complications in high-risk patients with colorectal cancer or dysplasia scheduled
      for elective colorectal resection: study protocol of a randomized controlled
      trial.

PMID- 29466956
TI  - Outcome and prognostic factors of patients with right-sided infective
      endocarditis requiring intensive care unit admission.
AB  - BACKGROUND: Right-sided infective endocarditis (RSIE) is an uncommon diagnosis
      accounting for less than 10% of cases of infective endocarditis. Optimal
      management for severely ill patients with RSIE remains challenging because few
      studies reported on management and outcome. The goal of our study was to
      determine outcome and associated prognostic factors in a population of ICU
      patients with a diagnosis of definite, active and severe RSIE. METHODS: We
      performed a retrospective study in 10 French ICUs between January 2002 and
      December 2012. Main outcome was mortality at 30 days after ICU admission.
      Significant variables associated with 30-days mortality in the bivariate analysis
      were included in a logistic regression analysis. RESULTS: A total of 37 patients
      were studied. Mean age was 47.9 +/- 18.4 years. Mean SAPS II, SOFA score and
      Charlson comorbidity index were 32.4 +/- 17.4, 6.3 +/- 4.4 and 3.1 +/- 3.4,
      respectively. Causative pathogens, identified in 34 patients, were mainly
      staphylococci (n = 29). The source of endocarditis was a catheter related
      infection in 10 patients, intravenous drug abuse in 8 patients, cutaneous in 7
      patients, urinary tract related in one patient and has an unknown origin in 7
      patients. Vegetation size was higher than 20 mm for 14 patients. Valve tricuspid
      regurgitation was classified as severe in 11 patients. All patients received
      initial appropriate antimicrobial therapy. Aminoglycosides were delivered in
      combination with beta-lactam antibiotics or vancomycin in 22 patients. Surgical
      procedure was performed in 14 patients. Eight patients (21.6%) died within 30
      days following ICU admission. One independent prognostic factor was identified:
      use of aminoglycosides was associated with improved outcome (OR = 0.1; 95%CI =
      0.0017-0.650; p = 0.007). CONCLUSION: Mortality of patients with RSIE needing ICU
      admission is high. Aminoglycosides used in combination with beta-lactam or
      vancomycin could reduce 30 days mortality.

PMID- 29466957
TI  - Altered DNA methylation in liver and adipose tissues derived from individuals
      with obesity and type 2 diabetes.
AB  - BACKGROUND: Obesity is a well-recognized risk factor for insulin resistance and
      type 2 diabetes (T2D), although the precise mechanisms underlying the
      relationship remain unknown. In this study we identified alterations of DNA
      methylation influencing T2D pathogenesis, in subcutaneous and visceral adipose
      tissues, liver, and blood from individuals with obesity. METHODS: The study
      included individuals with obesity, with and without T2D. From these patients, we
      obtained samples of liver tissue (n = 16), visceral and subcutaneous adipose
      tissues (n = 30), and peripheral blood (n = 38). We analyzed DNA methylation
      using Illumina Infinium Human Methylation arrays, and gene expression profiles
      using HumanHT-12 Expression BeadChip Arrays. RESULTS: Analysis of DNA methylation
      profiles revealed several loci with differential methylation between individuals
      with and without T2D, in all tissues. Aberrant DNA methylation was mainly found
      in the liver and visceral adipose tissue. Gene ontology analysis of genes with
      altered DNA methylation revealed enriched terms related to glucose metabolism,
      lipid metabolism, cell cycle regulation, and response to wounding. An inverse
      correlation between altered methylation and gene expression in the four tissues
      was found in a subset of genes, which were related to insulin resistance,
      adipogenesis, fat storage, and inflammation. CONCLUSIONS: Our present findings
      provide additional evidence that aberrant DNA methylation may be a relevant
      mechanism involved in T2D pathogenesis among individuals with obesity.

PMID- 29466958
TI  - Case presentation: implantation of cardiac resynchronization therapy pacemaker
      via the coronary sinus in a patient with triple valve replacement.
AB  - BACKGROUND: In patients with triple valve replacement developing third-degree
      atrioventricular block (AVB), the most appropriate approach for permanent
      pacemaker implantation remains questionable. CASE PRESENTATION: In this case
      presentation, we first described the approach of implantation of the cardiac
      resynchronization therapy pacemaker (CRT-P) via one bipolar pacing lead in middle
      cardiac vein (MCV) and one quadripolar pacing lead in anterior interventricular
      vein (AIV) in a patient developing complete AVB, who had been previously
      diagnosed with rheumatic valvular heart disease with triple valve replaced. After
      the CRT-P implantation, the two pacing leads in coronary sinus (CS) provided a
      dual-site ventricular pacing from the anterior septum and posterior septum, which
      resulted in a narrow QRS complex and an increased ventricular synchrony. During
      the long-term follow-up, no deterioration of heart function was documented and
      pacing parameters remained good. CONCLUSION: In this patient developing complete
      AVB with triple valve replaced, our approach of CRT-P implantation provides an
      effective and reliable ventricular pacing, and is an alternative option when
      transvenous right ventricular pacing, transseptal left ventricular pacing and
      transpericardial epicardium pacing are not possible. Further prospective
      randomized trials are required to confirm the efficiency of our approach of dual
      site ventricular pacing by CRT-P in this kind patients.

PMID- 29466959
TI  - "Self-development matters" - Perception of Sakhis (CHWs) assessing self
      development outcomes of their participation in the HBNC Program.
AB  - BACKGROUND: Community Health Workers (CHWs) play an instrumental role in
      promoting socio-behavioural change at the community level, which results in
      changed indicators of community health. While outcomes are mostly reviewed for
      achieving program objectives, it is pertinent to understand the process of
      program implementation mainly from the perception of participating CHWs. METHODS:
      A qualitative study to understand the perception of Sakhi's (CHWs) regarding the
      outcomes of their participation in Home-Based Neonatal Care (HBNC) Program
      implemented by a non-governmental organization (NGO). Data consisted of 3 FGDs
      and 20 in-depth unstructured interviews with participating Sakhis. RESULTS:
      Sakhis perceived their ability to take decisions at critical phases of the
      program as an important factor influencing their performance. The opportunity to
      participate as a Sakhi in the health programme initiated a process of change at
      the personal level. The changes perceived by Sakhis were enhancement in
      knowledge, skills and capabilities of Sakhis. The combination of improved skills,
      knowledge and attitude had culminated in the process of experiencing self
      empowerment for the participating Sakhis. Their ability to positively influence
      the individuals and community with their initiatives to improve women and child
      health and save lives in critical situations facilitated development of a new
      identity and improved societal status in their communities. Changed power
      relations at the family and community level promoted the involvement of Sakhis in
      the broader development agenda. Sakhis' ability to strategize goals, evaluate
      their own abilities, their willingness to upgrade knowledge and take others along
      in bringing social change, was an evident movement towards self-development.
      CONCLUSION: An opportunity for local women to participate in development programs
      creates potential for self-development as a cascading effect in addition to the
      accomplishment of planned program objective.

PMID- 29466960
TI  - High-dose of intravenous immunoglobulin modulates immune tolerance in premature
      infants.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) is commonly used to improve the
      immunomodulatory effects, although its regulatory effect on premature Treg cells
      is unclear. The purpose of this study is to study the effect of high dose of IVIG
      (HD-IVIG) on Treg cells expression and cytokine profile in premature birth.
      METHODS: Fifty-two premature infants were enrolled in this study and thirty-one
      premature infants who were suspected to have intrauterine infection received HD
      IVIG (1-2 g/kg) at the first day of birth; the remaining 21 premature infants
      were assigned as the control group. The peripheral blood CD4 + T and foxp3+ Treg
      cells were checked by flow cytometry, and cytokine concentrations were detected
      by cytometric bead array. RESULTS: With the gestational age growth, peripheral
      blood CD4 + T and foxp3+ Treg cells of prematurity gradually declined from 50% to
      35% and from 8% to 6%, respectively. Meanwhile, HD-IVIG increased the percentage
      of CD4 + T and foxp3+ Treg cells compared with their baseline levels (p < 0.001).
      HD-IVIG demonstrated different regulating effects on cytokines secretion,
      increased IL-17 and TGF-beta, and inhibited IL-6 secretion. CONCLUSION: Our
      results demonstrated that HD-IVIG not only enhanced the premature immune
      tolerance, but also suppressed the excessive inflammation response mediated by IL
      6. TRIAL REGISTRATION: This study was under the clinical study registration
      (ChiCTR-ORC-16008872, date of registration, 2016-07-21).

PMID- 29466961
TI  - A randomised trial to compare cognitive outcome after gamma knife radiosurgery
      versus whole brain radiation therapy in patients with multiple brain metastases:
      research protocol CAR-study B.
AB  - BACKGROUND: Gamma Knife radiosurgery (GKRS) is increasingly applied in patients
      with multiple brain metastases and is expected to have less adverse effects in
      cognitive functioning than whole brain radiation therapy (WBRT). Effective
      treatment with the least negative cognitive side effects is increasingly becoming
      important, as more patients with brain metastases live longer due to more and
      better systemic treatment options. There are no published randomized trials yet
      directly comparing GKRS to WBRT in patients with multiple brain metastases that
      include objective neuropsychological testing. METHODS: CAR-Study B is a
      prospective randomised trial comparing cognitive outcome after GKRS or WBRT in
      adult patients with 11-20 newly diagnosed brain metastases on a contrast-enhanced
      MRI-scan, KPS >=70 and life expectancy of at least 3 months. Randomisation by the
      method of minimization, is stratified by the cumulative tumour volume in the
      brain, systemic treatment, KPS, histology, baseline cognitive functioning and
      age. The primary endpoint is the between-group difference in the percentage of
      patients with significant memory decline at 3 months. Secondary endpoints include
      overall survival, local control, development of new brain metastases, cognitive
      functioning over time, quality of life, depression, anxiety and fatigue.
      Cognitive functioning is assessed by a standardised neuropsychological test
      battery. Assessments (cognitive testing, questionnaires and MRI-scans) are
      scheduled at baseline and at 3, 6, 9, 12 and 15 months after treatment.
      DISCUSSION: Knowledge gained from this trial may be used to inform individual
      patients with BM more precisely about the cognitive effects they can expect from
      treatment, and to assist both doctors and patients in making (shared) individual
      treatment decisions. This trial is currently recruiting. Target accrual: 23
      patients at 3-months follow-up in both groups. TRIAL REGISTRATION: The
      Netherlands Trials Register number NTR5463. ClinicalTrials.gov registration
      number NCT02953717 , first received October 27, 2016, 8 patients were enrolled in
      this study on 31 July 2017.

PMID- 29466962
TI  - The long non-coding RNA MYCNOS-01 regulates MYCN protein levels and affects
      growth of MYCN-amplified rhabdomyosarcoma and neuroblastoma cells.
AB  - BACKGROUND: MYCN is amplified in small cell lung cancers and several pediatric
      tumors, including alveolar rhabdomyosarcomas and neuroblastomas. MYCN protein is
      known to play a key oncogenic role in both alveolar rhabdomyosarcomas and
      neuroblastomas. MYCN opposite strand (MYCNOS) is a gene located on the antisense
      strand to MYCN that encodes alternatively spliced transcripts, two of which
      (MYCNOS-01 and MYCNOS-02) are known to be expressed in neuroblastoma and small
      cell lung cancer with reciprocal regulation between MYCNOS-02 and MYCN reported
      for neuroblastomas. We sought to determine a functional role for MYCNOS-01 in
      alveolar rhabdomyosarcoma and neuroblastoma cells and identify any associated
      regulatory effects between MYCN and MYCNOS-01. METHODS: MYCNOS-01, MYCNOS-02 and
      MYCN expression levels were assessed in alveolar rhabdomyosarcoma and
      neuroblastoma cell lines and tumor samples from patients using Affymetrix
      microarray data and quantitative RT-PCR. Following MYCNOS-01 or MYCN siRNA
      knockdown and MYCNOS-01 overexpression, transcript levels were assayed by
      quantitative RT-PCR and MYCN protein expression assessed by Western blot and
      immunofluorescence. Additionally, effects on cell growth, apoptosis and cell
      cycle profiles were determined by a metabolic assay, caspase activity and flow
      cytometry, respectively. RESULTS: MYCNOS-01 transcript levels were generally
      higher in NB and RMS tumor samples and cell lines with MYCN genomic
      amplification. RNA interference of MYCNOS-01 expression did not alter MYCN
      transcript levels but decreased MYCN protein levels. Conversely, MYCN reduction
      increased MYCNOS-01 transcript levels, creating a negative feedback loop on MYCN
      protein levels. Reduction of MYCNOS-01 or MYCN expression decreased cell growth
      in MYCN-amplified alveolar rhabdomyosarcoma and neuroblastoma cell lines. This is
      consistent with MYCNOS-01-mediated regulation of MYCN contributing to the
      phenotype observed. CONCLUSIONS: An alternative transcript of MYCNOS, MYCNOS-01,
      post-transcriptionally regulates MYCN levels and affects growth in MYCN-amplified
      rhabdomyosarcoma and neuroblastoma cells.

PMID- 29466963
TI  - Pediatric severe asthma: a case series report and perspectives on anti-IgE
      treatment.
AB  - BACKGROUND: The primary goal of asthma management is to achieve disease control
      for reducing the risk of future exacerbations and progressive loss of lung
      function. Asthma not responding to treatment may result in significant morbidity.
      In many children with uncontrolled symptoms, the diagnosis of asthma may be wrong
      or adherence to treatment may be poor. It is then crucial to distinguish these
      cases from the truly "severe therapy-resistant" asthmatics by a proper filtering
      process. Herein we report on four cases diagnosed as difficult asthma, detail the
      workup that resulted in the ultimate diagnosis, and provide the process that led
      to the prescription of omalizumab. CASE PRESENTATION: All children had been
      initially referred because of asthma not responding to long-term treatment with
      high-dose inhaled steroids, long-acting beta2-agonists and leukotriene receptor
      antagonists. Definitive diagnosis was severe asthma. Three out four patients were
      treated with omalizumab, which improved asthma control and patients' quality of
      life. We reviewed the current literature on the diagnostic approach to the
      disease and on the comorbidities associated with difficult asthma and presented
      the perspectives on omalizumab treatment in children and adolescents. Based on
      the evidence from the literature review, we also proposed an algorithm for the
      diagnosis of pediatric difficult-to-treat and severe asthma. CONCLUSIONS: The
      management of asthma is becoming much more patient-specific, as more and more is
      learned about the biology behind the development and progression of asthma. The
      addition of omalizumab, the first targeted biological treatment approved for
      asthma, has led to renewed optimism in the management of children and adolescents
      with atopic severe asthma.

PMID- 29466964
TI  - Successful treatment with pazopanib plus PD-1 inhibitor and RAK cells for
      advanced primary hepatic angiosarcoma: a case report.
AB  - BACKGROUND: Primary hepatic angiosarcoma (PHA) is a rare and aggressive solid
      tumor, with high rates of local recurrence and distant metastasis, and poor
      prognosis. There are no established treatment guidelines for PHA. CASE
      PRESENTATION: A 78-year-old asymptomatic man with PHA that was successfully
      treated with pazopanib plus PD-1 inhibitor and RetroNectin-activated killer cells
      (RAK cells). After one month of treatment, there was a clear reduction in the
      size and number of the liver metastases; and after nearly 15 months, most of the
      lesions were stable, no new lesions had developed, and the side effect of
      treatment was minor. CONCLUSION: Pazopanib, PD-1 inhibitor and RAK cells could
      serve as a potential option for the treatment of advanced PHA.

PMID- 29466965
TI  - Neutropenia after intravenous immunoglobulin therapy is associated with coronary
      artery lesions in children with Kawasaki disease: a case control study.
AB  - BACKGROUND: To evaluate differences in laboratory parameters, clinical
      presentation, and incidence of coronary artery lesions (CAL) between children
      with neutropenic and non-neutropenic Kawasaki disease (KD). METHODS: All
      consecutive KD patients that presented to the Second Affiliated Hospital and
      Yuying Children's Hospital of Wenzhou Medical University in Wenzhou, China
      between January 2005 and December 2015 were included in this study. Patients were
      divided into two groups (KD with neutropenia (NKD) and KD without neutropenia
      (NNKD)) based on whether or not they developed neutropenia during the course of
      treatment. We compared differences in clinical manifestations, laboratory
      parameters, and treatment protocols between groups. We also evaluated the
      relationship between neutropenia with immunoglobulin dosage and incidence of CAL.
      RESULTS: An IVIG treatment regimen of 2 g/kg*1d was associated with a lower
      incidence of neutropenia compared to the 1 g/kg*2d protocol. The incidence of CAL
      was higher in KD patients with neutropenia than in those without. Subgroup
      analysis showed no difference in the incidence of CAL among the different age
      groups between KD patients with and without neutropenia. CONCLUSIONS: Follow up
      ultrasonic echocardiography should be performed in KD patients with neutropenia
      in order to allow for early detection of CAL and timely intervention.

PMID- 29466966
TI  - Real life patterns of care and progression free survival in metastatic renal cell
      carcinoma patients: retrospective analysis of cross-sectional data.
AB  - BACKGROUND: Patient characteristics and survival outcomes in randomized trials
      may be different from those in real-life clinical practice. The objective of this
      study was to describe treatment pathways, safety, drug costs and survival in
      patients with metastatic Renal Cell Carcinoma (mRCC) in a real world setting.
      METHODS: A retrospective analysis was performed using IQVIA real world oncology
      cross-sectional survey data, a retrospective treatment database collecting
      anonymized patient-level data in Europe. Data on treatment naive patients with
      mRCC who received a first-line targeted therapy in France were extracted for the
      period 2005-2015. Descriptive analyses were performed on treatment patterns,
      patient characteristics and safety profiles. Progression Free Survival (PFS) was
      determined using Kaplan-Meier survival analysis. RESULTS: One thousand three
      hundred thirty-one patients with mRCC who received a first-line targeted therapy
      were included. The male/female sex ratio was 2.5 and 66% of patients were aged >
      60 years. 83% of patients had clear cell adenocarcinoma. 83% of patients
      underwent a surgical procedure, 10% had radiotherapy. In patients who received a
      first-line targeted therapy, 73% received sunitinib. The mean time from diagnosis
      to first-line treatment by targeted therapies in patients initially diagnosed
      with metastatic disease was 3.3 months [95% CI:2.5-4.1]. In patients who received
      second-line targeted therapy n = 257 (19%), the most frequently observed
      treatment sequences were sunitinib-everolimus (33%) and sunitinib-sorafenib
      (27%). Adverse events data were available for 501 patients and adverse events
      were documented in 70% of patients, most frequently diarrhoea. The overall median
      PFS was 13 months [95% CI:11.5-16]. CONCLUSION: Patient characteristics were
      consistent with the literature. Treatment patterns appeared to follow current
      practice guidelines. Despite some variations, PFS in our study seems to be
      consistent with findings from other real world studies. Nevertheless, PFS results
      were higher than those observed in clinical trials. Due to the use of cross
      sectional data, PFS in our study should be interpreted with caution.

PMID- 29466967
TI  - A pediatric death audit in a large referral hospital in Malawi.
AB  - BACKGROUND: Death audits have been used to describe pediatric mortality in under
      resourced settings, where record keeping is often a challenge. This information
      provides the cornerstone for the foundation of quality improvement initiatives.
      Malawi, located in sub-Saharan Africa, currently has an Under-5 mortality rate of
      64/1000. Kamuzu Central Hospital, in the capital city Lilongwe, is a busy
      government referral hospital, which admits up to 3000 children per month. A study
      published in 2013 reported mortality rates as high as 9%. This is the first known
      audit of pediatric death files conducted at this hospital. METHODS: A
      retrospective chart review on all pediatric deaths that occurred at Kamuzu
      Central Hospital (excluding deaths in the neonatal nursery) during a 13-month
      period was done using a standardized death audit form. A descriptive analysis was
      completed, including patient demographics, HIV and nutritional status, and cause
      of death. Modifiable factors were identified that may have contributed to
      mortality, including a lack of vital sign collection, poor documentation, and
      delays in the procurement or results of tests, studies, and specialist review.
      RESULTS: Seven hundred forty three total pediatric deaths were recorded and 700
      deceased patient files were reviewed. The mortality rate by month ranged from a
      low of 2.2% to a high of 4.4%. Forty-four percent of deaths occurred within the
      first 24 h of admission, and 59% occurred within the first 48 h. The most common
      causes of death were malaria, malnutrition, HIV-related illnesses, and sepsis.
      CONCLUSIONS: The mortality rate for this pediatric referral center has
      dramatically decreased in the 6 years since the last published mortality data,
      but remains high. Areas identified for continued development include improved
      record keeping, improved patient assessment and monitoring, and more timely and
      reliable provision of testing and treatment. This study demonstrates that in low
      resource settings, where reliable record keeping is often difficult, death audits
      are useful tools to describe the sickest patient population and determine factors
      possibly contributing to mortality that may be amenable to quality improvement
      interventions.

PMID- 29466968
TI  - Palliative care specialists' perceptions concerning referral of haematology
      patients to their services: findings from a qualitative study.
AB  - BACKGROUND: Haematological malignancies (leukaemias, lymphomas and myeloma) are
      complex cancers that are relatively common, affect all ages and have divergent
      outcomes. Although the symptom burden of these diseases is comparable to other
      cancers, patients do not access specialist palliative care (SPC) services as
      often as those with other cancers. To determine the reasons for this, we asked
      SPC practitioners about their perspectives regarding the barriers and
      facilitators influencing haematology patient referrals. METHODS: We conducted a
      qualitative study, set within the United Kingdom's (UK's) Haematological
      Malignancy Research Network (HMRN: www.hmrn.org ), a population-based cohort in
      the North of England. In-depth, semi-structured interviews were conducted with 20
      SPC doctors and nurses working in hospital, community and hospice settings
      between 2012 and 2014. Interviews were digitally audio-recorded, transcribed and
      analysed for thematic content using the 'Framework' method. RESULTS: Study
      participants identified a range of barriers and facilitators influencing the
      referral of patients with haematological malignancies to SPC services. Barriers
      included: the characteristics and pathways of haematological malignancies; the
      close patient/haematology team relationship; lack of role clarity; late end of
      life discussions and SPC referrals; policy issues; and organisational issues. The
      main facilitators identified were: establishment of inter-disciplinary working
      patterns (co-working) and enhanced understanding of roles; timely discussions
      with patients and early SPC referral; access to information platforms able to
      support information sharing; and use of indicators to 'flag' patients' needs for
      SPC. Collaboration between haematology and SPC was perceived as beneficial and
      desirable, and was said to be increasing over time. CONCLUSIONS: This is the
      first UK study to explore SPC practitioners' perceptions concerning haematology
      patient referrals. Numerous factors were found to influence the likelihood of
      referral, some of which related to the organisation and delivery of SPC services,
      so were amenable to change, and others relating to the complex and unique
      characteristics and pathways of haematological cancers. Further research is
      needed to assess the extent to which palliative care is provided by haematology
      doctors and nurses and other generalists and ways in which clinical uncertainty
      could be used as a trigger, rather than a barrier, to referral.

PMID- 29466969
TI  - Reliability and validity of measuring scale for postoperative complications in
      third molar surgery.
AB  - BACKGROUND: Third molar removal surgery is the most frequently performed surgery
      in the oral and maxillofacial field with a wide range of items in the
      quantification of postoperative complications. For their measure, in 2014 a
      previous scale design was presented. The aim of this study was to determine the
      reliability and validity of a scale designed to measure and quantify
      postoperative complications in third molar surgery (TMS). METHODS: A cross
      sectional study of a measurement model was designed. Sixty-two patients (mean age
      20.5 +/- 6.6 years; 36 women) underwent TMS in three Chilean hospitals. In the
      postoperative check-up on the 7th day, a maxillofacial surgeon and a surgical
      resident performed independent postoperative assessments, applying the scale. A
      confirmatory factor analysis was conducted to obtain validity, internal
      consistency, interobserver reliability and a score to categorize the severity of
      complications using structural equation model analysis. RESULTS: Nine patients
      (14.5%) had complications. The scale was defined by two components: "Secondary
      complication" and "Infection" (Cronbach's alpha 0.71; Interobserver reliability
      87.7%) and three categories of postoperative complication: "without or mild",
      "moderate" and "severe". CONCLUSION: This study presents a reliability and
      validity scale called "Surgical complication assessment scale in TMS".

PMID- 29466970
TI  - A novel combined systemic inflammation-based score can predict survival of
      intermediate-to-advanced hepatocellular carcinoma patients undergoing
      transarterial chemoembolization.
AB  - BACKGROUND: There is currently limited information regarding the prognostic
      ability of the dNLR-PNI (the combination of the derived neutrophil-to-lymphocyte
      ratio [dNLR] and prognostic nutritional index [PNI]) for hepatocellular carcinoma
      (HCC). This study aimed to assess the predictive ability of the dNLR-PNI in
      patients with intermediate-to-advanced HCC after transarterial chemoembolization
      (TACE). METHODS: A total of 761 HCC patients were enrolled in the study. The dNLR
      PNI was retrospectively calculated in these patients, as follows: patients with
      both an elevated dNLR and a decreased PNI, as determined using the cutoffs
      obtained from receiver operating characteristic curve analysis, were allocated a
      score of 2, while patients showing one or neither of these alterations were
      allocated a score of 1 or 0, respectively. RESULTS: During the follow-up period,
      562 patients died. Multivariate analysis suggested that elevated total bilirubin,
      Barcelona Clinic Liver Cancer C stage, repeated TACE, and dNLR-PNI were
      independently associated with unsatisfactory overall survival. The median
      survival times of patients with a dNLR-PNI of 0, 1, and 2 were 31.0 (95%
      confidence interval [CI] 22.5-39.5), 16.0 (95% CI 12.2-19.7) and 6.0 (95% CI 4.8
      7.2) months, respectively (P < 0.001). CONCLUSIONS: The dNLR-PNI can predict the
      survival outcomes of intermediate-to-advanced HCC patients undergoing TACE, and
      should be further evaluated as a prognostic marker for who are to undergo TACE
      treatment.

PMID- 29466971
TI  - Perioperative dynamics and significance of plasma-free amino acid profiles in
      colorectal cancer.
AB  - BACKGROUND: For early detection of cancer, we have previously developed the
      AminoIndex Cancer Screening (AICS) system, which quantifies 6 plasma-free amino
      acids (PFAAs) in blood samples. Herein, we examined the usefulness of the AICS in
      patients with colorectal cancer (CRC) by comparing the preoperative and
      postoperative PFAA profiles. METHODS: Our study cohort consisted of 62 patients
      who had undergone curative resection for CRC at our cancer center, with no
      recurrence at the time of the study. Blood samples were collected from fasted
      patients within 1 week before the resection and at 0.5-6.5 years post-resection.
      Following plasmapheresis, the PFAA levels were measured via liquid
      chromatography/mass spectrometry, and the AICS values were computed (the higher
      the value, the greater the probability of cancer). Risk was calculated from the
      AICS value and ranked as A, B, or C, with rank C representing the highest risk.
      All patients in our study were rank B + C. RESULTS: The postoperative AICS value
      was lower than the preoperative value in 57 of the 62 patients; the rank was also
      lower postoperatively (49 patients, p < 0.001). The decline in both was stage
      independent, even occurring in patients with right-sided tumors or poorly
      differentiated adenocarcinomas. For comparative purposes, the levels of 2 tumor
      markers (carbohydrate antigen 19-9 and carcinoembryonic antigen) were also
      examined; these were within the reference ranges in 70-80% of patients
      preoperatively and in 80-90% postoperatively. CONCLUSION: We suggest that tumor
      bearing conditions alter the PFAA profiles, which may be used to predict
      prognosis and monitor for recurrence in CRC patients after tumor resection. TRIAL
      REGISTRATION: This trial has been retrospectively registered at UMIN-CTR
      R000028005 , Oct 06, 2016.

PMID- 29466972
TI  - Is there a causal effect of parity on body composition: a birth cohort study.
AB  - BACKGROUND: Non-communicable diseases are the leading cause of death, worldwide.
      Obesity is one of the factors that is associated with the development of such
      diseases. The role of reproductive factors on women body composition has been
      evaluated, but the findings are controversial. This study was aimed at assessing
      the association of parity with body composition among women. METHODS: In 1982,
      the maternity hospital of Pelotas, a southern Brazilian city, were visited daily
      and all deliveries were identified. Those livebirths whose family lived in the
      urban area of the city have been prospectively followed (n = 5914). In 2012-13,
      we tried to follow the whole cohort, the subjects were interviewed and examined.
      We evaluated the association of parity with the following body composition
      variables: body mass index, waist circumference and fat mass %. Estimates were
      adjusted for family income, skin color, maternal schooling, occupational status,
      alcohol, smoking, physical activity, and consumption of processed and
      ultraprocessed foods. All these analyses were replicated among the cohort men as
      a comparison. We also assessed whether duration of breastfeeding moderated the
      association. RESULTS: In the 2012-13 visit, 3701 subjects were evaluated (mean
      age of 30.2 years). In the present analysis, we included 1620 women and 1653 men.
      33% of women were nulliparous and 48% of men were without children. Even after
      controlling for confounding, parous women had a BMI 0.96 kg/m2 (95% CI: 0.30;
      1.62) higher than nulliparous and for men the regression coefficient was 0.79
      kg/m2 (95% CI: 0.29; 1.29). Waist circumference was also higher among parous
      women. Among men, the association was not linear and the regression coefficients
      were lower than that observed among women [3.41 cm (95% CI: -0.91; 7.73) among
      men and 4.83 cm (95% CI: 2.43; 7.24) among women with more than 3 children when
      compared with those without children], but this difference was not statistically
      significant (interaction p value = 0.58). Fat mass % was not associated with
      parity. Breastfeeding did not modify the association between parity and body
      composition. CONCLUSIONS: Parity was positively associated with body mass index
      and waist circumference among women. However, similar results among men suggest
      that there is no causal effect of parity.

PMID- 29466973
TI  - Occurrence of colorectal aberrant crypt foci depending on age and dietary
      patterns of patients.
AB  - BACKGROUND: Aberrant crypt foci (ACF) are commonly considered the early pre
      cancerous lesions that can progress to colorectal cancer (CRC). The available
      literature data reveal that age, dietary factors and lifestyle can affect the
      development of several dozen percentages of malignant tumours, including CRC. In
      the present study, an attempt was made to assess the incidence and growth
      dynamics of ACF and to determine whether the type of diet affected the
      development and number of AFC. METHODS: Colonoscopy combined with rectal mucosa
      staining with 0.25% methylene blue was performed in 131 patients. On the day of
      examination, each patient completed a questionnaire regarding epidemiological
      data. According to their numbers, colorectal ACF were divided into three groups.
      The findings were analysed statistically. The Student's t test and the U test
      were applied in order to determine the significance of differences of means and
      frequency of events in both groups. Statistica 7.1 and Excel 2010 were used.
      RESULTS: The single ACF occur in the youngest individuals (ACF < 5). Since the
      age of 38 years, the number of ACF gradually increases to show a decreasing
      tendency since the age of 60 years. The number of 5 < ACF < 10 occurs slightly
      later, since the age of 50 years, and dynamically increases reaching the maximum
      at the age of 62 years, subsequently the increase is proportional. ACF > 10 occur
      at a more advanced age (55 years) and their number gradually increases with age.
      The maximum number is observed at the age of 77 years. In individuals not using
      high-fibre diets and with high intake of red meat, the probability of higher
      numbers of ACF increases. The probability of higher numbers of ACF (5 < ACF10)
      was observed in patients with colon diverticula. In patients with higher BMI, the
      number of ACF is higher. CONCLUSION: Age significantly affects the number of
      colorectal ACF. The types of foods consumed can considerably increase the risk of
      colorectal ACF, which is particularly visible in individuals who do not regularly
      use high-fibre diets, those obese and with colon diverticula.

PMID- 29466974
TI  - Temporary employment and tooth loss: a cross-sectional study from the J-SHINE
      study.
AB  - BACKGROUND: Temporary employment leads to psychological distress and higher
      mortality, but data on its associations with oral health is limited. We examined
      whether having the experience of temporary employment was associated with tooth
      loss among working adults in Japan. METHODS: We conducted a cross-sectional study
      from the 2010-2011 Japanese Study on Stratification, Health, Income, and
      Neighborhood study that analyzed 2652 participants aged 25-50 years (men = 1394;
      women = 1258). Independent variable was changes in employment status (continuous
      regular employment and the experience of temporary employment). Dependent
      variable was self-reported tooth loss (none, 1 tooth, 2 teeth, 3 teeth, 4 teeth,
      and more than 4 teeth). Covariates were sex, age, years of education, self-rated
      household economic status in early life at 5 years old, marital status, number of
      family members in the household, history of diabetes, and body mass index. We
      conducted a negative binomial regression analysis to estimate prevalence rate
      ratios (PRRs) and 95% confidence intervals (95%CIs) for tooth loss. We also
      confirmed the interaction term between changes in employment status and sex.
      RESULTS: The median age of the participants was 37 years. The percentages of men
      and women who experienced temporary employment were 14.5% and 61.3%,
      respectively. Compared with continuous regular employment, the experience of
      temporary employment was significantly associated with tooth loss in both sexes
      after adjusting for the covariates (men: PRR = 1.50 [95%CI = 1.13, 2.00]; women:
      PRR = 1.42 [95%CI = 1.14, 1.76]). The interaction term between employment status
      and sex was not significant (p = 0.71). CONCLUSIONS: Temporary employment is
      adversely associated with oral health.

PMID- 29466975
TI  - The impact of alcohol among injury patients in Moshi, Tanzania: a nested case
      crossover study.
AB  - BACKGROUND: Globally, alcohol is responsible for 3.3 million deaths annually and
      contributes to 5.9% of the overall global burden of disease. In Sub-Saharan
      Africa, alcohol is the leading avoidable risk factor accounting for a substantial
      portion of death and disability. This project aimed to determine the proportion
      of injuries related to alcohol and the increased risk of injury due to alcohol
      among injury patients seeking care at the emergency department (ED) of
      Kilimanjaro Christian Medical Centre (KCMC) in Moshi, Tanzania. METHODS: A
      representative cross-sectional sample of adult patients presenting to the KCMC ED
      with acute injury were enrolled in this study with a nested case-crossover
      design. Patient demographics, injury characteristics, and severity as well as
      alcohol use behaviors were collected. Alcohol breathalyzers were administered to
      the enrolled patients. Data on activities and alcohol use were collected for the
      time period 6 h prior to injury and two control periods: 24-30 h prior to injury
      and 1 week prior to injury. RESULTS: During 47 weeks of data collection, 24,070
      patients were screened, of which 2164 suffered injuries, and 516 met the
      inclusion and exclusion criteria, consented to participate, and had complete
      data. Of the study participants, 76% were male, and 30% tested positive for
      alcohol on arrival to the ED. Alcohol use was associated with being male and
      being employed. Alcohol use was associated with an increased risk of injury (OR
      5.71; 95% CI 3.84-8.50), and specifically road traffic injuries were associated
      with the highest odds of injury with alcohol use (OR 6.53, 95% CI 3.98-10.71).
      For all injuries and road traffic injuries specifically, we found an increase in
      the odds of injury with an incremental increase in the dose of alcohol.
      CONCLUSIONS: At KCMC in Moshi, Tanzania, 3 of 10 injury patients tested positive
      for alcohol on presentation for care. Similarly, alcohol use conveys an increased
      risk for injury in this setting. Evidence-based prevention strategies for alcohol
      related injuries need to be implemented to reduce alcohol misuse and alcohol
      related injuries.

PMID- 29466976
TI  - Predicting the distribution of Stipa purpurea across the Tibetan Plateau via the
      MaxEnt model.
AB  - BACKGROUND: The ecosystems across Tibetan Plateau are changing rapidly under the
      influence of climate warming, which has caused substantial changes in spatial and
      temporal environmental patterns. Stipa purpurea, as a dominant herbsage resource
      in alpine steppe, has a great influence on animal husbandry in the Tibetan
      Plateau. Global warming has been forecasted to continue in the future (2050s,
      2070s), questioning the future distribution of S. purpurea and its response to
      climate change. The maximum entropy (MaxEnt) modeling, due to its multiple
      advantages (e.g. uses presence-only data, performs well with incomplete data, and
      requires small sample sizes and gaps), has been used to understand species
      environment relationships and predict species distributions across locations that
      have not been sampled. RESULTS: Annual mean temperature, annual precipitation,
      temperature seasonality, altitude, and precipitation during the driest month,
      significantly affected the distribution of S. purpurea. Only 0.70% of the Tibetan
      Plateau area included a very highly suitable habitat (habitat suitability [HS] =
      0.8-1.0). Highly suitable habitat (HS = 0.6-0.8), moderately suitable habitat (HS
      = 0.4-0.6), and unsuitable habitat (HS = 0.2-0.4) occupied 6.20, 14.30 and 22.40%
      of the Tibetan Plateau area, respectively, and the majority (56.40%) of the
      Tibetan Plateau area constituted a highly unsuitable habitat (HS = 0-0.2). In
      addition, the response curves of species ecological suitability simulated by
      generalized additive model nearly corresponded with the response curves generated
      by the MaxEnt model. CONCLUSIONS: At a temporal scale, the habitat suitability of
      S. purpurea tends to increase from the 1990s to 2050s, but decline from the 2050s
      to 2070s. At a spatial scale, the future distribution of S. purpurea will not
      exhibit sweeping changes and will remain in the central and southeastern regions
      of the Tibetan Plateau. These results benefit the local animal husbandry and
      provide evidence for establishing reasonable management practices.

PMID- 29466977
TI  - The Rotterdam Elderly Pain Observation Scale (REPOS) is reliable and valid for
      non-communicative end-of-life patients.
AB  - BACKGROUND: In palliative care, administration of opioids is often indispensable
      for pain treatment. Pain assessment may help recognize pain and guide treatment
      in non-communicative patients. In the Netherlands the Rotterdam Elderly Pain
      Observation Scale (REPOS) is recommended to this aim, but not yet validated.
      Therefore the objective of this study was to validate the REPOS in non
      communicative or unconscious end-of-life patients. METHODS: In this observational
      study, the primary researcher applied the REPOS, while both the researcher and a
      nurse applied the Numeric Rating Scale (NRS). If possible, the patient in
      question applied the NRS as well. The NRS scores were compared with the REPOS
      scores to determine concurrent validity. REPOS scores obtained before and after a
      pain-reducing intervention were analysed to establish the scale's sensitivity to
      change. RESULTS: A total of 183 REPOS observations in 100 patients were analysed.
      Almost 90% of patients had an advanced malignancy; observations were done a
      median of 3 days (IQR 1 to 13) before death. Internal consistency of the REPOS
      was 0.73. The Pearson product moment correlation coefficient ranged from 0.64 to
      0.80 between REPOS and NRS scores. REPOS scores declined with median 2 points
      (IQR 1 to 4) after a pain-reducing intervention (p < 0.001). Optimal sensitivity
      (0.81) and specificity (0.62) were found at cut-off score 3. CONCLUSIONS: This
      study demonstrates that the REPOS has promising psychometric properties for pain
      assessment in non-communicative end-of-life patients. Its application may be of
      additional value to relieve suffering, including pain, in palliative care.

PMID- 29466978
TI  - Repeated electroacupuncture treatment attenuated hyperalgesia through suppression
      of spinal glial activation in chronic neuropathic pain rats.
AB  - BACKGROUND: Cumulated evidence reveals that glial cells in the spinal cord play
      an important role in the development of chronic neuropathic pain and are also
      complicated in the analgesic effect of EA intervention. But the roles of
      microgliacytes and astrocytes of spinal cord in the process of EA analgesia
      remain unknown. METHODS: A total of 120 male Wistar rats were used in the present
      study. The neuropathic pain model was established by chronic constrictive injury
      (CCI) of the sciatic nerve. The rats were randomly divided into sham group, CCI
      group, and sham CCI + EA group, and CCI + EA group. EA was applied to bilateral
      Zusanli (ST36)-Yanlingquan (GB34). The mechanical (both time and force responses)
      and thermal pain thresholds (PTs) of the bilateral hind-paws were measured. The
      number of microgliacytes and activity of astrocytes in the dorsal horns (DHs) of
      lumbar spinal cord (L4-5) were examined by immunofluorescence staining, and the
      expression of glial fibrillary acidic protein (GFAP) protein was detected by
      western blot. RESULTS: Following CCI, both mechanical and thermal PTs of the
      ipsilateral hind-paw were significantly decreased beginning from the 3rd day
      after surgery (P < 0.05), and the mechanical PT of the contralateral hind-paw was
      considerably decreased from the 6th day on after surgery (P < 0.05). CCI also
      significantly upregulated the number of Iba-1 labeled microgliacytes and the
      fluorescence intensity of glial fibrillary acidic protein (GFAP) -labeled
      astrocyte in the superficial laminae of DHs on bilateral sides (P < 0.05). After
      repeated EA, the mechanical and thermal PTs at bilateral hind-paws were
      significantly relieved (P < 0.05). The increased of number of microgliacytes was
      markedly suppressed by 2 days' EA intervention, and the average fluorescence
      intensity was suppressed by 2 weeks' EA. The expression of GFAP protein were down
      regulated by 1 and 2 weeks' EA treatment, respectively (P < 0.05). CONCLUSIONS:
      Repeated EA can relieve neuropathic pain and mirror-image pain in chronic
      neuropathic pain rats, which is probably associated with its effect in
      downregulating glial cell activation of the lumbar spinal cord, the microgliacyte
      first and astrocyte later.

PMID- 29466979
TI  - The high need for trials assessing functional outcome after stroke rather than
      stroke prevention with GLP-1 agonists and DPP-4 inhibitors.

PMID- 29466980
TI  - The benefits of co-location in primary care practices: the perspectives of
      general practitioners and patients in 34 countries.
AB  - BACKGROUND: There is no clear evidence as to whether the co-location of primary
      care professionals in the same facility positively influences their way of
      working and the quality of healthcare as perceived by patients. The aim of this
      study was to identify the relationships between general practitioner (GP) co
      location with other GPs and/or other professionals and the GP outcomes and
      patients' experiences. METHODS: We wanted to test whether GP co-location is
      related to a broader range of services provided, the use of clinical governance
      tools and inter-professional collaboration, and whether the patients of co
      located GPs perceive a better quality of care in terms of accessibility,
      comprehensiveness and continuity of care with their GPs. The source of data was
      the QUALICOPC study (Quality and Costs of Primary Care in Europe), which involved
      surveys of GPs and their patients in 34 countries, mostly in Europe. In order to
      study the relationships between GP co-location and both GPs' outcomes and
      patients' experience, multilevel linear regression analysis was carried out.
      RESULTS: The GP questionnaire was filled in by 7183 GPs and the patient
      experience questionnaire by 61,931 patients. Being co-located with at least one
      other professional is the most common situation of the GPs involved in the study.
      Compared with single-handed GP practices, GP co-location are positively
      associated with the GP outcomes. Considering the patients' perspective,
      comprehensiveness of care has the strongest negative relationship of GP co
      location of all the dimensions of patient experiences analysed. CONCLUSIONS: The
      paper highlights that GP mono- and multi-disciplinary co-location is related to
      positive outcomes at a GP level, such as a broader provision of technical
      procedures, increased collaboration among different providers and wider
      coordination with secondary care. However, GP co-location, particularly in a
      multidisciplinary setting, is related to less positive patient experiences,
      especially in countries with health systems characterised by a weak primary care
      structure.

PMID- 29466981
TI  - A novel purified Lactobacillus acidophilus 20079 exopolysaccharide, LA-EPS-20079,
      molecularly regulates both apoptotic and NF-kappaB inflammatory pathways in human
      colon cancer.
AB  - BACKGROUND: The direct link between inflammatory bowel diseases and colorectal
      cancer is well documented. Previous studies have reported that some lactic acid
      bacterial strains could inhibit colon cancer progression however; the exact
      molecules involved have not yet been identified. So, in the current study, we
      illustrated the tumor suppressive effects of the newly identified Lactobacillus
      acidophilus DSMZ 20079 cell-free pentasaccharide against colon cancer cells. The
      chemical structure of the purified pentasaccharide was investigated by MALDI-TOF
      mass spectrum, 1D and 2D Nuclear Magnetic Resonance (NMR). The anticancer
      potentiality of the purified pentasaccharide against both Human colon cancer
      (CaCo-2) and Human breast cancer (MCF7) cell lines with its safety usage pattern
      were evaluated using cytotoxicity, annexin V quantification and BrdU
      incorporation assays. Also, the immunomodulatory effects of the identified
      compound were quantified on both LPS-induced PBMC cell model and cancer cells
      with monitoring the immunophenotyping of T and dendritic cell surface marker. At
      molecular level, the alteration in gene expression of both inflammatory and
      apoptotic pathways were quantified upon pentasaccharide-cellular treatment by
      RTqPCR. RESULTS: The obtained data of the spectroscopic analysis, confirmed the
      structure of the newly extracted pentasaccharide; (LA-EPS-20079) to be: alpha-D
      Glc (1->2)][alpha-L-Fuc(1->4)] alpha-D-GlcA(1->2) alpha-D-GlcA(1->2) alpha-D
      GlcA. This pentasaccharide, recorded safe dose on normal mammalian cells ranged
      from 2 to 5 mg/ml with cancer cells selectivity index, ranged of 1.96-51.3. Upon
      CaCo-2 cell treatment with the non-toxic dose of LA-EPS-20079, the inhibition
      percentage in CaCo-2 cellular viability, reached 80.65 with an increase in the
      ratio of the apoptotic cells in sub-G0/G1 cell cycle phase. Also, this
      pentasaccharide showed potentialities to up-regulate the expression of IKbalpha,
      P53 and TGF genes. CONCLUSION: The anticancer potentialities of LA-EPS-20079
      oligosaccharides against human colon cancer represented through its regulatory
      effects on both apoptotic and NF-kappaB inflammatory pathways.

PMID- 29466982
TI  - Early-life exposure to PM2.5 and risk of acute asthma clinical encounters among
      children in Massachusetts: a case-crossover analysis.
AB  - BACKGROUND: Associations between ambient particulate matter < 2.5 MUm (PM2.5) and
      asthma morbidity have been suggested in previous epidemiologic studies but
      results are inconsistent for areas with lower PM2.5 levels. We estimated the
      associations between early-life short-term PM2.5 exposure and the risk of asthma
      or wheeze clinical encounters among Massachusetts children in the innovative
      Pregnancy to Early Life Longitudinal (PELL) cohort data linkage system. METHODS:
      We used a semi-bidirectional case-crossover study design with short-term exposure
      lags for asthma exacerbation using data from the PELL system. Cases included
      children up to 9 years of age who had a hospitalization, observational stay, or
      emergency department visit for asthma or wheeze between January 2001 and
      September 2009 (n = 33,387). Daily PM2.5 concentrations were estimated at a 4-km
      resolution using satellite remote sensing, land use, and meteorological data. We
      applied conditional logistic regression models to estimate adjusted odds ratios
      (ORs) and 95% confidence intervals (CI). We also stratified by potential effect
      modifiers. RESULTS: The median PM2.5 concentration among participants was 7.8
      MUg/m3 with an interquartile range of 5.9 MUg/m3. Overall, associations between
      PM2.5 exposure and asthma clinical encounters among children at lags 0, 1 and 2
      were close to the null value of OR = 1.0. Evidence of effect modification was
      observed by birthweight for lags 0, 1 and 2 (p < 0.05), and season of clinical
      encounter for lags 0 and 1 (p < 0.05). Children with low birthweight (LBW) (<
      2500 g) had increased odds of having an asthma clinical encounter due to higher
      PM2.5 exposure for lag 1 (OR: 1.08 per interquartile range (IQR) increase in
      PM2.5; 95% CI: 1.01, 1.15). CONCLUSION: Asthma or wheeze exacerbations among LBW
      children were associated with short-term increases in PM2.5 concentrations at low
      levels in Massachusetts.

PMID- 29466984
TI  - Correction to: Inhibition of autophagy enhances synergistic effects of
      Salidroside and anti-tumor agents against colorectal cancer.
AB  - CORRECTION: The authors of this article [1] would like the funding and
      acknowledgements to be disregarded.

PMID- 29466983
TI  - Multidrug-resistant tuberculosis treatment adherence in migrants: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a growing concern in
      meeting global targets for TB control. In high-income low-TB-incidence countries,
      a disproportionate number of MDR-TB cases occur in migrant (foreign-born)
      populations, with concerns about low adherence rates in these patients compared
      to the host non-migrant population. Tackling MDR-TB in this context may,
      therefore, require unique approaches. We conducted a systematic review and meta
      analysis to identify and synthesise data on MDR-TB treatment adherence in migrant
      patients to inform evidence-based strategies to improve care pathways and health
      outcomes in this group. METHODS: This systematic review and meta-analysis was
      conducted in line with PRISMA guidelines (PROSPERO 42017070756). The databases
      Embase, MEDLINE, Global Health and PubMed were searched to 24 May 2017 for
      primary research reporting MDR-TB treatment adherence and outcomes in migrant
      populations, with no restrictions on dates or language. A meta-analysis was
      conducted using random-effects models. RESULTS: From 413 papers identified in the
      database search, 15 studies reporting on MDR-TB treatment outcomes for 258
      migrants and 174 non-migrants were included in the systematic review and meta
      analysis. The estimated rate of adherence to MDR-TB treatment across migrant
      patients was 71% [95% confidence interval (CI) = 58-84%], with non-adherence
      reported among 20% (95% CI = 4-37%) of migrant patients. A key finding was that
      there were no differences in estimated rates of adherence [risk ratio (RR) =
      1.05; 95% CI = 0.82-1.34] or non-adherence (RR = 0.97; 95% CI = 0.79-1.36)
      between migrants and non-migrants. CONCLUSIONS: MDR-TB treatment adherence rates
      among migrants in high-income low-TB-incidence countries are approaching global
      targets for treatment success (75%), and are comparable to rates in non-migrants.
      The findings highlight that only just over 70% of migrant and non-migrant
      patients adhere to MDR-TB treatment. The results point to the importance of
      increasing adherence in all patient groups, including migrants, with an emphasis
      on tailoring care based on social risk factors for poor adherence. We believe
      that MDR-TB treatment targets are not ambitious enough.

PMID- 29466985
TI  - Association between plasma fatty acids and inflammatory markers in patients with
      and without insulin resistance and in secondary prevention of cardiovascular
      disease, a cross-sectional study.
AB  - BACKGROUND: Proinflammatory biomarkers levels are increased among patients with
      cardiovascular disease, and it is known that both the presence of insulin
      resistance and diet may influence those levels. However, these associations are
      not well studied among patients with established cardiovascular disease. Our
      objective is to compare inflammatory biomarker levels among cardiovascular
      disease secondary prevention patients with and without insulin resistance, and to
      evaluate if there is any association between plasma fatty acid levels and
      inflammatory biomarker levels among them. METHODS: In this cross-sectional sub
      study from the BALANCE Program Trial, we collected data from 359 patients with
      established cardiovascular disease. Plasma fatty acids and inflammatory
      biomarkers (interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, high sensitive C
      reactive protein (hs-CRP), adiponectin, and tumor necrosis factor (TNF)-alpha)
      were measured. Biomarkers and plasma fatty acid levels of subjects across insulin
      resistant and not insulin resistant groups were compared, and general linear
      models were used to examine the association between plasma fatty acids and
      inflammatory biomarkers. RESULTS: Subjects with insulin resistance had a higher
      concentration of hs-CRP (p = 0.002) and IL-6 (p = 0.002) than subjects without
      insulin resistance. Among subjects without insulin resistance there was a
      positive association between stearic fatty acid and IL-6 (p = 0.032), and a
      negative association between alpha-linolenic fatty acid and pro-inflammatory
      biomarkers (p < 0.05). Among those with insulin resistance there was a positive
      association between monounsaturated fatty acids and arachidonic fatty acid and
      adiponectin (p < 0.05), and a negative association between monounsaturated and
      polyunsaturated fatty acids and pro-inflammatory biomarkers (p < 0.05), as well
      as a negative association between polyunsaturated fatty acids and adiponectin (p
      < 0.05). Our study has not found any association between hs-CRP and plasma fatty
      acids. CONCLUSIONS: Subjects in secondary prevention for cardiovascular disease
      with insulin resistance have a higher concentration of hs-CRP and IL-6 than
      individuals without insulin resistance, and these inflammatory biomarkers are
      positively associated with saturated fatty acids and negatively associated with
      unsaturated fatty acids.

PMID- 29466986
TI  - The role of kinesin KIF18A in the invasion and metastasis of hepatocellular
      carcinoma.
AB  - BACKGROUND: KIF18A is associated with a variety of tumours; however, the specific
      mechanism of action of KIF18A in hepatocellular carcinoma (HCC) remains unclear.
      In this study, in vitro and in vivo experiments were performed with the aim of
      exploring the potential function and molecular mechanism of kinesin KIF18A in the
      occurrence and development of HCC. METHODS: We detected the expression of KIF18A
      in tumour and adjacent tissues as well as cell proliferation, cell invasion and
      migration in hepatoma cells after silencing KIF18A. KIF18A-silenced hepatoma
      cells were subcutaneously injected into nude mice to verify the tumorigenicity of
      KIF18A. We also detected the expression of signal pathway-related proteins in
      hepatoma cells after KIF18A knockdown with the aim of exploring the association
      between KIF18A and related signalling pathways. RESULTS: The level of KIF18A
      protein was higher in liver cancer tissues than adjacent tissues. After silencing
      KIF18A in SMMC-7721 and HepG2 cells, cell growth was obviously inhibited; the
      migration and invasion abilities were significantly decreased and the in vivo
      tumour weight was decreased compared to the control group (0.201 +/- 0.088 g vs
      0.476 +/- 0.126 g, p = 0.009). The expression of cell cycle-related protein
      (cyclin B1), invasion and metastasis-related proteins (MMP-7 and MMP-9) and Akt
      related proteins in hepatoma cells was also decreased after knocking down KIF18A.
      CONCLUSIONS: KIF18A may promote proliferation, invasion and metastasis of HCC
      cells by promoting the cell cycle signalling pathway as well as the Akt and MMP
      7/MMP-9-related signalling pathways and may serve as a new target for the
      diagnosis and treatment of HCC.

PMID- 29466987
TI  - Antioxidant capacities and total phenolic contents of 20 polyherbal remedies used
      as tonics by folk healers in Phatthalung and Songkhla provinces, Thailand.
AB  - BACKGROUND: Uses of polyherbal formulations have played a major role in
      traditional medicine. The present study is focused on the formulations used in
      traditional Thai folkloric medicine as tonics or bracers. Twenty documented
      polyherbal mixtures, used as nourishing tonics by the folk healers in Phatthalung
      and Songkhla provinces in southern Thailand, are targeted. Despite traditional
      health claims, there is no scientific evidence to support the utilization of
      polyherbal formulations. METHODS: The phenolic and flavonoid contents of the
      polyherbal formulations and a series of antioxidant tests were applied to measure
      their capability as preventive or chain-breaking antioxidants. In addition, the
      cytotoxic activity of effective formulations was assayed in Vero cells. RESULTS:
      Ninety-eight plant species belonging to 45 families were used to prepare the
      tested formulation. The preliminary results revealed that water extracts of THP
      R016 and THP-R019 contain a high level of total phenolic and flavonoid contents
      and exhibit remarkable antioxidant activities, as tested by DPPH, ABTS, and FRAP
      assays. The extract of THP-R019 also showed the strongest metal chelating
      activities, whereas THP-R016 extract possessed notable superoxide anion and
      peroxyl radical scavenging abilities. CONCLUSIONS: The data provide evidence that
      the water extracts of folkloric polyherbal formulations, particularly THP-R016,
      are a potential source of natural antioxidants, which will be valuable in the
      pharmaceutical and nutraceutical industries. The free radical scavenging of THP
      R016 may be due to the contribution of phenolic and flavonoid contents. Useful
      characteristics for the consumer, such as the phytochemical profiles of active
      ingredients, cellular based antioxidant properties and beneficial effects in
      vivo, are under further investigation.

PMID- 29466988
TI  - Blood flow characteristics of diabetic patients with complications detected by
      optical measurement.
AB  - BACKGROUND: Diabetes mellitus (DM) is one of the most common diseases worldwide.
      Uncontrolled and prolonged hyperglycemia can cause diabetic complications, which
      reduce the quality of life of patients. Diabetic complications are common in DM
      patients. Because it is impossible to completely recover from diabetic
      complications, it is important for early detection. In this study, we suggest a
      novel method of determining blood flow characteristics based on fluorescence
      image analysis with indocyanine green and report that diabetic complications have
      unique blood flow characteristics. METHODS: We analyzed time-series fluorescence
      images obtained from controls, DM patients, and DM patients with complications.
      The images were segmented into the digits and the dorsum of the feet and hands,
      and each part has been considered as arterial and capillary flow. We compared the
      blood flow parameters in each region among the three groups. RESULTS: The DM
      patients with complications showed similar blood flow parameters to the controls,
      except the area under the curve and the maximum intensity, which indicate the
      blood flow volume. These parameters were significantly decreased in DM patients
      with complications. Although some blood flow parameters in the feet of DM
      patients with complications were close to normal blood flow, the vascular
      response of the macrovessels and microvessels to stimulation of the hands was
      significantly reduced, which indicates less reactivity in DM patients with
      complications. CONCLUSIONS: Our results suggest that DM patients, and DM patients
      with complications, have unique peripheral blood flow characteristics.

PMID- 29466989
TI  - Sweet attraction: sugarcane pollen-associated volatiles attract gravid Anopheles
      arabiensis.
AB  - BACKGROUND: Anopheles arabiensis is a key vector for the transmission of human
      malaria in sub-Saharan Africa. Over the past 10,000 years, humans have
      successfully cultivated grasses and altered the landscape, creating An.
      arabiensis favourable environments that contain excellent habitats for both
      larvae and adults. Sugarcane is the most expanding agricultural system in sub
      Saharan Africa, and is linked to the increased threat of malaria in rural
      communities. The prolific production and wind dispersal of sugarcane pollen,
      together with standing pools of water, often provide, as a result of irrigation,
      a nutrient-rich environment for the offspring of gravid malaria mosquitoes.
      RESULTS: In the present study, sugarcane pollen-associated volatiles from two
      cultivars are shown to attract gravid An. arabiensis in a still air two-port
      olfactometer and stimulate egg laying in an oviposition bioassay. Through
      combined gas chromatography and electroantennographic detection, as well as
      combined gas chromatography and mass spectrometric analyses, we identified the
      bioactive volatiles and generated a synthetic blend that reproduced the full
      behavioural repertoire of gravid mosquitoes in the Y-tube assay. Two subtractive
      odour blends, when compared with the full blend, were significantly more
      attractive. These three and four-component subtractive blends share the compounds
      (1R)-(+)-alpha-pinene, nonanal and benzaldehyde, of which, (1R)-(+)-alpha-pinene
      and nonanal are found in the attractive odour blends from rice plants and maize
      pollen. In pairwise comparisons, the rice synthetic odour blend was more
      attractive to gravid mosquitoes than either of the pollen blends, whereas the
      pollen blends did not differ in attraction. CONCLUSIONS: The attraction of gravid
      females to sugarcane pollen volatiles demonstrated in this study, together with
      the previously found grass-associated volatiles, raise the potential of
      developing a bioactive chimeric blend to attract gravid malaria mosquitoes. This
      is discussed in relation to the development of novel and cost-effective vector
      control measures.

PMID- 29466990
TI  - Targeting HER2-breast tumors with scFv-decorated bimodal nanoprobes.
AB  - BACKGROUND: Recent advances in nanomedicine have shown the great interest of
      active targeting associated to nanoparticles. Single chain variable fragments
      (scFv) of disease-specific antibodies are very promising targeting entities
      because they are small, not immunogenic and able to bind their specific antigens.
      The present paper is devoted to biological properties in vitro and in vivo of
      fluorescent and pegylated iron oxide nanoparticles (SPIONs-Cy-PEG-scFv)
      functionalized with scFv targeting Human Epithelial growth Receptor 2 (HER2).
      RESULTS: Thanks to a site-selective scFv conjugation, the resultant nanoprobes
      demonstrated high affinity and specific binding to HER2 breast cancer cells. The
      cellular uptake of SPIONs-Cy-PEG-scFv was threefold higher than that for
      untargeted PEGylated iron oxide nanoparticles (SPIONs-Cy-PEG) and is correlated
      to the expression of HER2 on cells. In vivo, the decrease of MR signals in HER2+
      xenograft tumor is about 30% at 24 h after the injection. CONCLUSIONS: These
      results all indicate that SPIONs-Cy-PEG-scFv are relevant tumor-targeting
      magnetic resonance imaging agents, suitable for diagnosis of HER2 overexpressing
      breast tumor.

PMID- 29466991
TI  - Asymptomatic Plasmodium vivax parasitaemia in the low-transmission setting: the
      role for a population-based transmission-blocking vaccine for malaria
      elimination.
AB  - Plasmodium vivax remains an important cause of morbidity and mortality across the
      Americas, Horn of Africa, East and South East Asia. Control of transmission has
      been hampered by emergence of chloroquine resistance and several intrinsic
      characteristics of infection including asymptomatic carriage, challenges with
      diagnosis, difficulty eradicating the carrier state and early gametocyte
      appearance. Complex human-parasite-vector immunological interactions may
      facilitate onward infection of mosquitoes. Given these challenges, new therapies
      are being explored including the development of transmission to mosquito blocking
      vaccines. Herein, the case supporting the need for transmission-blocking vaccines
      to augment control of P. vivax parasite transmission and explore factors that are
      limiting eradication efforts is discussed.

PMID- 29466992
TI  - The HNF1alpha-regulated lncRNA HNF1A-AS1 reverses the malignancy of
      hepatocellular carcinoma by enhancing the phosphatase activity of SHP-1.
AB  - BACKGROUND: Our previous study has demonstrated that hepatocyte nuclear factor
      1alpha (HNF1alpha) exerts potent therapeutic effects on hepatocellular carcinoma
      (HCC). However, the molecular mechanisms by which HNF1alpha reverses HCC
      malignancy need to be further elucidated. METHODS: lncRNA microarray was
      performed to identify the long noncoding RNAs (lncRNAs) regulated by HNF1alpha.
      Chromatin immunoprecipitation and luciferase reporter assays were applied to
      clarify the mechanism of the transcriptional regulation of HNF1alpha to HNF1A
      antisense RNA 1 (HNF1A-AS1). The effect of HNF1A-AS1 on HCC malignancy was
      evaluated in vitro and in vivo. RNA pulldown, RNA-binding protein
      immunoprecipitation and the Bio-Layer Interferometry assay were used to validate
      the interaction of HNF1A-AS1 and Src homology region 2 domain-containing
      phosphatase 1 (SHP-1). RESULTS: HNF1alpha regulated the expression of a subset of
      lncRNAs in HCC cells. Among these lncRNAs, the expression levels of HNF1A-AS1
      were notably correlated with HNF1alpha levels in HCC cells and human HCC tissues.
      HNF1alpha activated the transcription of HNF1A-AS1 by directly binding to its
      promoter region. HNF1A-AS1 inhibited the growth and the metastasis of HCC cells
      in vitro and in vivo. Moreover, knockdown of HNF1A-AS1 reversed the suppressive
      effects of HNF1alpha on the migration and invasion of HCC cells. Importantly,
      HNF1A-AS1 directly bound to the C-terminal of SHP-1 with a high binding affinity
      (KD = 59.57 +/- 14.29 nM) and increased the phosphatase activity of SHP-1.
      Inhibition of SHP-1 enzymatic activity substantially reversed the HNF1alpha- or
      HNF1A-AS1-induced reduction on the metastatic property of HCC cells. CONCLUSIONS:
      Our data revealed that HNF1A-AS1 is a direct transactivation target of HNF1alpha
      in HCC cells and involved in the anti-HCC effect of HNF1alpha. HNF1A-AS1
      functions as phosphatase activator through the direct interaction with SHP-1.
      These findings suggest that regulation of the HNF1alpha/HNF1A-AS1/SHP-1 axis may
      have beneficial effects in the treatment of HCC.

PMID- 29466993
TI  - Greenhouse gas emissions of self-selected diets in the UK and their association
      with diet quality: is energy under-reporting a problem?
AB  - BACKGROUND: While the admittedly limited number of epidemiological findings on
      the association between diet-related greenhouse gas emissions (GHGE) and diet
      quality are not always consistent, potential influence of bias in the estimation
      of diet-related GHGE caused by misreporting of energy intake (EI) has not been
      investigated. This cross-sectional study evaluated diet-related GHGE in the UK
      and their association with diet quality, taking account of EI under-reporting.
      METHODS: Dietary data used were from the National Diet and Nutrition Survey
      rolling programme 2008/2009-2013/2014, in which 4-day food diaries were collected
      from 3502 adults aged >=19 years. Diet-related GHGE were estimated based on 133
      food groups, using GHGE values from various secondary sources. Diet quality was
      assessed by the healthy diet indicator (HDI), Mediterranean diet score (MDS) and
      Dietary Approaches to Stop Hypertension (DASH) score. EI misreporting was
      assessed as reported EI divided by estimated energy requirement (EI:EER).
      RESULTS: Mean value of daily GHGE was 5.7 kg carbon dioxide equivalents (CO2eq),
      which is consistent with those reported from a number of national representative
      samples in other European countries. Mean EI:EER was 0.74. Assuming that all the
      dietary variables were misreported in proportion to the misreporting of EI, the
      mean value of the misreporting-adjusted diet-related GHGE was 8.2 kg CO2eq/d. In
      the entire population, after adjustment for potential confounders (i.e., age,
      sex, ethnicity, socioeconomic classification, smoking status and physical
      activity), diet-related GHGE were inversely associated with HDI and DASH score
      but not with MDS. However, with further adjustment for EI:EER, diet-related GHGE
      showed inverse associations with all three measures of diet quality. Similar
      associations were observed when only under-reporters (EI:EER < 0.70; n = 1578)
      were analysed. Conversely, in the analysis including only plausible reporters
      (EI:EER 0.70-1.43; n = 1895), diet-related GHGE showed inverse associations with
      all diet quality measures irrespective of adjustment. CONCLUSIONS: With taking
      account of EI under-reporting, this study showed inverse associations between
      diet-related GHGE and diet quality not only in the entire sample but also in the
      separate analyses of plausible reporters and under-reporters, as well as
      potential underreporting of diet-related GHGE.

PMID- 29466994
TI  - Developing a framework to evaluate knowledge into action interventions.
AB  - BACKGROUND: There are many challenges in delivering and evaluating knowledge for
      healthcare, but the lack of clear routes from knowledge to practice is a root
      cause of failures in safety within healthcare. Various types and sources of
      knowledge are relevant at different levels within the healthcare system. These
      need to be delivered in a timely way that is useful and actionable for those
      providing services or developing policies. How knowledge is taken up and used
      through networks and relationships, and the difficulties in attributing change to
      knowledge-based interventions, present challenges to understanding how knowledge
      into action (K2A) work influences healthcare outcomes. This makes it difficult to
      demonstrate the importance of K2A work, and harness support for its development
      and resourcing. This paper presents the results from a project commissioned by
      NHS Education for Scotland (NES) and Healthcare Improvement Scotland (HIS) to
      create an evaluation framework to help understand the NHS Scotland Knowledge into
      Action model. METHODS: The team took a developmental approach to creating an
      evaluation framework that would be useful and practical. This included a
      literature review to ensure the evaluation was evidence-based; adaptation of
      contribution analysis for K2A project; action research with K2A project leads to
      refine the work and develop suitable measures. RESULTS: Principles for evaluation
      and an evaluation framework based on contribution analysis were developed and
      implemented on a trial project. An outcomes chain was developed for the K2A
      programme and specific projects. This was used to design, collect and collate
      evidence of the K2A intervention. Data collected routinely by the intervention
      was supplemented with specific feedback measures from K2A project users.
      CONCLUSIONS: The evaluation approach allowed for scrutiny of both processes and
      outcomes and was adaptable to projects on different scales. This framework has
      proved useful as a planning, reflecting and evaluation tool for K2A, and could be
      more widely used to evidence the ways in which knowledge to action work helps
      improve healthcare outcomes.

PMID- 29466995
TI  - Nothing in cancer makes sense except....
AB  - Paraphrasing Dobzhansky's famous dictum, I discuss how interrogating cancer
      through the lens of evolution has transformed our understanding of its
      development, causality and treatment resistance. The emerging picture of cancer
      captures its extensive diversity and therapeutic resilience, highlighting the
      need for more innovative approaches to control.

PMID- 29466996
TI  - 'Just because she's young, it doesn't mean she has to die': exploring the
      contributing factors to high maternal mortality in adolescents in Eastern
      Freetown; a qualitative study.
AB  - BACKGROUND: In Sierra Leone, 34% of pregnancies and 40% of maternal deaths are in
      the adolescent population. Risks are known to be higher for younger adolescents,
      this being borne out by a household survey in Eastern Freetown in 2015. This
      current qualitative study, funded by Wellbeing of Women's international midwifery
      fellowship, was conducted to explore the causes of this high incidence of
      maternal death for younger teenagers, and to identify possible interventions to
      improve outcomes. METHODS: This qualitative study used semi-structured interviews
      (n = 19) and focus groups (n = 6), with a wide range of professional and lay
      participants, recorded with consent. Recordings were transcribed by the first
      author and a Krio-speaking colleague where necessary, and Nvivo software was used
      to assist with theming of the data around the three main research questions.
      RESULTS: Themes from discussions on vulnerability to teenage pregnancy focused on
      transactional sex, especially for girls living outside of their birth family.
      They included sex for school fees, sex with teachers for grades, sex for food and
      clothes, and sex to lessen the impact of the time-consuming duties of water
      collection and petty trading. In addition, the criminal justice system and the
      availability and accessibility of contraception and abortion were included within
      this major theme. Within the major theme of vulnerability to death once pregnant,
      abandonment, delayed care seeking, and being cared for by a non-parental adult
      were identified. Several obstetric risks were discussed by midwives, but were
      explicitly related to the socio-economic factors already mentioned. A cross
      cutting theme throughout the data was of gendered social norms for sexual
      behaviour, for both boys and girls, being reinforced by significant adults such
      as parents and teachers. CONCLUSION: Findings challenge the notion that
      adolescent girls have the necessary agency to make straightforward choices about
      their sexual behaviour and contraceptive use. For girls who do become pregnant,
      risks are believed to be related more to stigma and abandonment than to physical
      maturity, leading to lack of family-based support and delayed care-seeking for
      antenatal and delivery care. Two potential interventions identified within the
      research are a mentoring scheme for the most vulnerable pregnant girls and a
      locally managed blood donation register. A feasibility study of a pilot mentoring
      scheme is currently underway, run by the first author and a local partner.

PMID- 29466997
TI  - Hearing impairment in MELAS: new prospective in clinical use of microRNA, a
      systematic review.
AB  - AIM: To evaluate the feasibility of microRNAs (miR) in clinical use to fill in
      the gap of current methodology commonly used to test hearing impairment in MELAS
      patients. MATERIAL AND METHOD: A literature review was performed using the
      following keywords, i.e., MELAS, Hearing Loss, Hearing Impairment, Temporal Bone,
      Otoacustic Emission (OTOAE), Auditory Brain Response (ABR), and microRNA. We
      reviewed the literature and focused on the aspect of the temporal bone, the
      results of electrophysiological tests in human clinical studies, and the use of
      miR for detecting lesions in the cochlea in patients with MELAS. RESULTS: In
      patients with MELAS, Spiral Ganglions (SG), stria vascularis (SV), and hair cells
      are damaged, and these damages affect in different ways various structures of the
      temporal bone. The function of these cells is typically investigated using OTOAE
      and ABR, but in patients with MELAS these tests provide inconsistent results,
      since OTOAE response is absent and ABR is normal. The normal ABR responses are
      unexpected given the SG loss in the temporal bone. Recent studies in humans and
      animals have shown that miRs, and in particular miRs 34a, 29b, 76, 96, and 431,
      can detect damage in the cells of the cochlea with high sensitivity. Studies that
      focus on the temporal bone aspects have reported that miRs increase is correlated
      with the death of specific cells of the inner ear. MiR - 9/9* was identified as a
      biomarker of human brain damage, miRs levels increase might be related to damage
      in the central auditory pathways and these increased levels could identify the
      damage with higher sensitivity and several months before than
      electrophysiological testing. CONCLUSION: We suggest that due to their accuracy
      and sensitivity, miRs might help monitor the progression of SNHL in patients with
      MELAS.

PMID- 29466998
TI  - Contextually tailored interventions can increase evidence-informed policy-making
      on health-enhancing physical activity: the experiences of two Danish
      municipalities.
AB  - BACKGROUND: The present study aims to test out contextually tailored
      interventions to increase evidence-informed health-enhancing physical activity
      policy-making in two Danish municipalities. METHODS: The study was performed as
      experiments in natural settings. Based on results from a pre-intervention study
      defining the needs and contexts of the two settings, the interventions were
      developed based on logical models. The interventions aimed at increasing the use
      of knowledge in policy-making, primarily via strengthening intersectoral
      collaboration. The interventions were evaluated via pre-, post- and 12-month
      follow-up questionnaires and qualitative interviews were carried out prior to the
      intervention start. RESULTS: The use of knowledge changed in several ways. In one
      municipality, the use of stakeholder and target group knowledge increased
      whereas, in the other municipality, the use of research knowledge increased. In
      both municipalities, the ability to translate knowledge to local context, the
      political request and the organisational procedures for use of knowledge
      increased during the interventions. There was some variation between the two
      settings, which shows the importance of tailoring to context. Most of the changes
      were diminished at the 12-month follow-up. CONCLUSION: Contextually tailored
      interventions have the potential to increase evidence-informed policy-making on
      health-enhancing physical activity. However, this finding needs to be tested in
      larger samples and its sustainability must be strengthened.

PMID- 29466999
TI  - A probiotic complex, rosavin, zinc, and prebiotics ameliorate intestinal
      inflammation in an acute colitis mouse model.
AB  - BACKGROUND: An altered gut microbiota balance is involved in the pathogenesis of
      inflammatory bowel disease (IBD), and several probiotic strains are used as
      dietary supplements to improve intestinal health. We evaluated the therapeutic
      effect of 12 probiotics in combination with prebiotics, rosavin, and zinc in the
      dextran sodium sulfate (DSS)-induced colitis mouse model. METHODS: The probiotic
      complex or the combination drug was administered orally to mice with DSS-induced
      colitis, and the body weight, disease activity index, colon length, and
      histopathological parameters were evaluated. Also, the combination drug was
      applied to HT-29 epithelial cells, and the expression of monocyte chemoattractant
      protein 1 (MCP-1) was evaluated by real-time polymerase chain reaction. RESULTS:
      Administration of the combination drug attenuated the severity of DSS-induced
      colitis. Moreover, the combination drug significantly reduced the levels of the
      proinflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-6, IL
      1beta, and IL-17, and significantly increased the levels of Foxp3 and IL-10 in
      colon sections. Additionally, treatment with the combination drug reduced MCP-1
      expression in HT-29 cells. Treatment with the combination drug decreased the
      levels of alpha-smooth muscle actin and type I collagen compared with vehicle
      treatment in mice with DSS-induced colitis. CONCLUSION: These results suggest
      that the combination of a probiotic complex with rosavin, zinc, and prebiotics
      exerts a therapeutic effect on IBD by modulating production of pro- and anti
      inflammatory cytokines and the development of fibrosis.

PMID- 29467000
TI  - Ginsenoside Re protects methamphetamine-induced dopaminergic neurotoxicity in
      mice via upregulation of dynorphin-mediated kappa-opioid receptor and
      downregulation of substance P-mediated neurokinin 1 receptor.
AB  - BACKGROUND: We previously reported that ginsenoside Re (GRe) attenuated against
      methamphetamine (MA)-induced neurotoxicity via anti-inflammatory and antioxidant
      potentials. We also demonstrated that dynorphin possesses anti-inflammatory and
      antioxidant potentials against dopaminergic loss, and that balance between
      dynorphin and substance P is important for dopaminergic neuroprotection. Thus, we
      examined whether GRe positively affects interactive modulation between dynorphin
      and substance P against MA neurotoxicity in mice. METHODS: We examined changes in
      dynorphin peptide level, prodynorphin mRNA, and substance P mRNA, substance P
      immunoreactivity, homeostasis in enzymatic antioxidant system, oxidative
      parameter, microglial activation, and pro-apoptotic parameter after a neurotoxic
      dose of MA to clarify the effects of GRe, prodynorphin knockout, pharmacological
      inhibition of kappa-opioid receptor (i.e., nor-binaltorphimine), or neurokinin 1
      (NK1) receptor (i.e., L-733,060) against MA insult in mice. RESULTS: GRe
      attenuated MA-induced decreases in dynorphin level, prodynorphin mRNA expression
      in the striatum of wild-type (WT) mice. Prodynorphin knockout potentiated MA
      induced dopaminergic toxicity in mice. The imbalance of enzymatic antioxidant
      system, oxidative burdens, microgliosis, and pro-apoptotic changes led to the
      dopaminergic neurotoxicity. Neuroprotective effects of GRe were more pronounced
      in prodynorphin knockout than in WT mice. Nor-binaltorphimine, a kappa-opioid
      receptor antagonist, counteracted against protective effects of GRe. In addition,
      we found that GRe significantly attenuated MA-induced increases in substance P
      immunoreactivity and substance P mRNA expression in the substantia nigra. These
      increases were more evident in prodynorphin knockout than in WT mice. Although,
      we observed that substance P-immunoreactivity was co-localized in NeuN
      immunreactive neurons, GFAP-immunoreactive astrocytes, and Iba-1-immunoreactive
      microglia. NK1 receptor antagonist L-733,060 or GRe selectively inhibited
      microgliosis induced by MA. Furthermore, L-733,060 did not show any additive
      effects against GRe-mediated protective activity (i.e., antioxidant,
      antimicroglial, and antiapoptotic effects), indicating that NK1 receptor is one
      of the molecular targets of GRe. CONCLUSIONS: Our results suggest that GRe
      protects MA-induced dopaminergic neurotoxicity via upregulatgion of dynorphin
      mediated kappa-opioid receptor and downregulation of substance P-mediated NK1 R.

PMID- 29467001
TI  - Neuregulin-1 elicits a regulatory immune response following traumatic spinal cord
      injury.
AB  - BACKGROUND: Spinal cord injury (SCI) triggers a robust neuroinflammatory response
      that governs secondary injury mechanisms with both degenerative and pro
      regenerative effects. Identifying new immunomodulatory therapies to promote the
      supportive aspect of immune response is critically needed for the treatment of
      SCI. We previously demonstrated that SCI results in acute and permanent depletion
      of the neuronally derived Neuregulin-1 (Nrg-1) in the spinal cord. Increasing the
      dysregulated level of Nrg-1 through acute intrathecal Nrg-1 treatment enhanced
      endogenous cell replacement and promoted white matter preservation and functional
      recovery in rat SCI. Moreover, we identified a neuroprotective role for Nrg-1 in
      moderating the activity of resident astrocytes and microglia following injury. To
      date, the impact of Nrg-1 on immune response in SCI has not yet been
      investigated. In this study, we elucidated the effect of systemic Nrg-1 therapy
      on the recruitment and function of macrophages, T cells, and B cells, three major
      leukocyte populations involved in neuroinflammatory processes following SCI.
      METHODS: We utilized a clinically relevant model of moderately severe compressive
      SCI in female Sprague-Dawley rats. Nrg-1 (2 MUg/day) or saline was delivered
      subcutaneously through osmotic mini-pumps starting 30 min after SCI. We conducted
      flow cytometry, quantitative real-time PCR, and immunohistochemistry at acute,
      subacute, and chronic stages of SCI to investigate the effects of Nrg-1 treatment
      on systemic and spinal cord immune response as well as cytokine, chemokine, and
      antibody production. RESULTS: We provide novel evidence that Nrg-1 promotes a pro
      regenerative immune response after SCI. Bioavailability of Nrg-1 stimulated a
      regulatory phenotype in T and B cells and augmented the population of M2
      macrophages in the spinal cord and blood during the acute and chronic stages of
      SCI. Importantly, Nrg-1 fostered a more balanced microenvironment in the injured
      spinal cord by attenuating antibody deposition and expression of pro-inflammatory
      cytokines and chemokines while upregulating pro-regenerative mediators.
      CONCLUSION: We provide the first evidence of a significant regulatory role for
      Nrg-1 in neuroinflammation after SCI. Importantly, the present study establishes
      the promise of systemic Nrg-1 treatment as a candidate immunotherapy for
      traumatic SCI and other CNS neuroinflammatory conditions.

PMID- 29467002
TI  - Intraocular DHODH-inhibitor PP-001 suppresses relapsing experimental uveitis and
      cytokine production of human lymphocytes, but not of RPE cells.
AB  - BACKGROUND: Uveitis is a potentially blinding inflammatory disease of the inner
      eye with a high unmet need for new therapeutic interventions. Here, we wanted to
      investigate the suppressive effect of the intraocular application of the small
      molecule dihydroorotate dehydrogenase (DHODH)-inhibitor PP-001 on experimental
      relapsing rat uveitis and furthermore determine its effect on proliferation and
      cytokine secretion of human peripheral blood lymphocytes (PBL) and human retinal
      pigment epithelial (RPE) cells in vitro. METHODS: Spontaneously relapsing uveitis
      was induced in rats by immunization with interphotoreceptor retinoid-binding
      protein (IRBP) peptide R14. PP-001 was injected intravitreally after resolution
      of the primary disease to investigate further relapses. Proliferation and
      metabolic activity of phytohemagglutinin (PHA)-stimulated human peripheral
      lymphocytes with and without PP-001 and cytokine secretion were determined by XTT
      assay and bioplex bead assay. The RPE cell line ARPE-19 as well as primary human
      RPE cells treated with PP-001 or anti-vascular endothelial growth factor (VEGF)
      antibody bevacizumab were also investigated for metabolic activity and
      cytokine/chemokine secretion. RESULTS: Injection of PP-001 into rat eyes reduced
      the number of relapses by 70%, from 20 relapses (57% of the rats affected) in the
      control group to 6 relapses (33% of the rats) in the treatment group. In human
      PBL cultures, PP-001 reduced the proliferation in a dose-dependent manner. The
      secretion of several cytokines such as IL-17, IFN-gamma, and VEGF was suppressed
      by PP-001, as previously observed with rat T cells in the experimental autoimmune
      uveitis (EAU) model. In contrast, human RPE cells were not affected by PP-001,
      while the anti-VEGF antibody bevacizumab severely impaired the secretion of
      various cytokines including VEGF. CONCLUSIONS: For the first time, intravitreal
      injection of PP-001 demonstrated an effective, but transient reduction of
      relapses in the rat EAU model. In vitro PP-001 suppressed proliferation and
      cytokine/chemokine secretion of human lymphocytes, while neither human RPE cell
      line ARPE-19 nor primary RPE cells were affected.

PMID- 29467003
TI  - Extracellular alpha-synuclein levels are regulated by neuronal activity.
AB  - BACKGROUND: alpha-Synuclein is a presynaptic protein abundant in the cytoplasmic
      compartment of neurons, whereas its presence in the extracellular space has also
      been observed under physiological conditions. Extracellular alpha-synuclein has
      pathological significance, exhibiting cellular toxicity and impairment of
      synaptic transmission. Notably, misfolded alpha-synuclein drives the cell-to-cell
      propagation of pathology via the extracellular space. However, the primary
      mechanism that regulates the extracellular levels of alpha-synuclein remains to
      be determined. METHODS: Using several mechanistically distinct methods to
      modulate neuronal/synaptic activities in primary neuronal culture and in vivo
      microdialysis, we examined the involvement of neuronal/synaptic activities on
      alpha-synuclein release. RESULTS: We demonstrate here that physiological release
      of endogenous alpha-synuclein highly depends on intrinsic neuronal activities.
      Elevating neuronal activity rapidly increased, while blocking activity decreased,
      alpha-synuclein release. In vivo microdialysis experiments in freely moving mice
      revealed that ~ 70% of extracellular alpha-synuclein arises from neuronal
      activity-dependent pathway. Selective modulation of glutamatergic
      neurotransmission altered extracellular alpha-synuclein levels, implicating this
      specific neuronal network in the mechanism of activity-dependent release of alpha
      synuclein. While neuronal activity tightly regulated alpha-synuclein release,
      elevated synaptic vesicle exocytosis per se was capable to elicit alpha-synuclein
      release. We also found that extracellular alpha-synuclein exists as high
      molecular weight species. CONCLUSIONS: The present study uncovers a novel
      regulatory pathway associated with alpha-synuclein release, whose dysregulation
      might affect various pathological actions of extracellular alpha-synuclein
      including its trans-synaptic propagation.

PMID- 29467004
TI  - Orf virus infection in Alaskan mountain goats, Dall's sheep, muskoxen, caribou
      and Sitka black-tailed deer.
AB  - BACKGROUND: The zoonotic Orf virus (ORFV; genus Parapoxvirus, Poxviridae family)
      occurs worldwide and is transmitted between sheep and goats, wildlife and man.
      Archived tissue samples from 16 Alaskan wildlife cases, representing mountain
      goat (Oreamnos americanus, n = 8), Dall's sheep (Ovis dalli dalli, n = 3), muskox
      (Ovibos moschatus, n = 3), Sitka black-tailed deer (Odocoileus hemionus
      sitkensis, n = 1) and caribou (Rangifer tarandus granti, n = 1), were analyzed.
      RESULTS: Clinical signs and pathology were most severe in mountain goats,
      affecting most mucocutaneous regions, including palpebrae, nares, lips, anus,
      prepuce or vulva, as well as coronary bands. The proliferative masses were solid
      and nodular, covered by dark friable crusts. For Dall's sheep lambs and
      juveniles, the gross lesions were similar to those of mountain goats, but not as
      extensive. The muskoxen displayed ulcerative lesions on the legs. The caribou had
      two ulcerative lesions on the upper lip, as well as lesions on the distal part of
      the legs, around the main and dew claws. A large hairless spherical mass, with
      the characteristics of a fibroma, was sampled from a Sitka black-tailed deer,
      which did not show proliferative lesions typical of an ORFV infection. Polymerase
      chain reaction analyses for B2L, GIF, vIL-10 and ATI demonstrated ORFV specific
      DNA in all cases. Sequences from Dall's sheep formed a separate cluster,
      comparable to ORFV from domestic sheep. Sequences from the other species were
      different from the Dall's sheep sequences, but almost identical to each other.
      CONCLUSIONS: This is the first major investigation of parapoxvirus infections in
      large Alaskan game species, and the first report of parapoxvirus infection in
      caribou and Sitka black-tailed deer. This study shows that most of the wild
      ruminant species in Alaska and from most parts of Alaska, can carry and be
      affected by ORFV. These findings call for attention to transmission of ORFV from
      wildlife to livestock and to hunters, subsistence harvesters, and wildlife
      biologists.

PMID- 29467005
TI  - Traditional knowledge on herbal drinks among indigenous communities in Azad Jammu
      and Kashmir, Pakistan.
AB  - BACKGROUND: Traditional knowledge about the use of medicinal plants for herbal
      drinks (HDs) is not well documented in the Azad Kashmir region despite their
      widespread use. This study highlights the taxonomic diversity and traditional
      knowledge on medicinal plants used for HDs while examining the diversity of
      diseases treated with HDs in the study area. METHODS: Individual discussions were
      conducted with 255 informants (84 women and 171 men). Data gathered included (i)
      informant age and gender, (ii) HD species and respective plant parts used, (iii)
      health disorders treated, and (iv) mode of preparation and utilizations.
      Quantitative ethnobotanical indices including relative frequency of citation
      (RFC), informant consensus factor (ICF), and use value (UV) were used for data
      analyses. RESULTS: Altogether, 73 medicinal plants belonging to 40 families and
      66 genera were reported to be used in HD preparations, with Asteraceae being the
      richest family. The average number of HD species cited was 9.09 +/- 0.17 per
      informant and did not vary either by age or gender. In addition, men and women,
      and adults and the young used the same pool of species (dissimilarity nearly
      zero). The most used plant parts were leaves (20.00%), roots (17.25%), and fruits
      (16.47%). Based on UV, the top five most used species were Valeriana jatamansi,
      Isodon rugosus, Onopordum acanthium, Acacia nilotica, and Viola canescens; and
      the UV was similar among gender and age categories too. The most utilized herbal
      preparation forms included decoctions, infusions, and tea. One hundred and eleven
      diseases grouped into 13 ailment categories were reported to be cured using HDs.
      The main category of disease treated with HDs was gastrointestinal (GIT)
      disorders (RFC = 17.43%). Relatively few species were used by a large proportion
      of informants for each category of ailment (ICF >= 0.60). Only one species was
      used for "glandular disorders" and "eye diseases" (ICF = 1). A novelty of about
      22% (16 species) was recorded for HD species in the present work. CONCLUSION: The
      diversity of medicinal plant species used as HDs and the associated traditional
      knowledge are of considerable value to the indigenous communities of the Azad
      Kashmir region. Therefore, there is a need for conservation and preservation of
      medicinal HD species as well as the wealth of indigenous knowledge. The
      conservation effort should be high for species in the ailments categories
      glandular disorders and eye diseases. The therapeutic uses of HDs have provided
      basic data for further research focused on phytochemical and pharmacological
      studies and conservation of the most important species.

PMID- 29467006
TI  - Associations within school-based same-sex friendship networks of children's
      physical activity and sedentary behaviours: a cross-sectional social network
      analysis.
AB  - BACKGROUND: Physical activity in children is associated with better physical and
      mental health but many children do not meet physical activity guidelines.
      Friendship groups are potentially an important influence on children's physical
      activity and sedentary time. This paper examines the association between children
      of physical activity and sedentary time in school-based same-sex friendship
      networks, for both moderate-to-vigorous intensity physical activity (MVPA) and
      sedentary time. Moreover, considering the methodological challenges of conducting
      and interpreting these analyses, we provide examples of how to analyse these data
      and interpret results to encourage further work in the area. METHODS:
      Accelerometer data for 1223 children, aged 8-9 years, were collected in 2015-2016
      and analysed in 2017. Mean accelerometer minutes of MVPA and sedentary time were
      calculated. Children named up to four school friends and same-sex school-based
      friendship networks were constructed. Network models, which include correlation
      between friends, were fitted by sex. RESULTS: Both MVPA and sedentary time were
      found to be associated via the friendship networks, for both boys and girls. The
      network autocorrelation was 0.21 (95% CI: 0.15 to 0.26) for boys' MVPA, and 0.14
      (95% CI: 0.07 to 0.21) for sedentary time. Network autocorrelation between girls
      was weaker, with 0.13 (95% CI: 0.06 to 0.19) for MVPA and 0.11 (95% CI: 0.05 to
      0.17) for sedentary time. CONCLUSIONS: Physical activity and sedentary time of
      boys and girls are associated with the physical activity and sedentary time
      respectively of others within same-sex friendship networks, and these
      associations are comparable to other known factors. In this study, the
      correlation between friends was stronger for boys than girls, and stronger for
      MVPA than for sedentary time. These findings suggest that friendship networks
      play a part in understanding children's physical activity and sedentary time and
      could play a valuable role in developing effective interventions.

PMID- 29467007
TI  - Enhanced glycolysis contributes to the pathogenesis of experimental autoimmune
      neuritis.
AB  - BACKGROUND: With the recognition of the key roles of cellular metabolism in
      immunity, targeting metabolic pathway becomes a new strategy for autoimmune
      disease treatment. Guillain-Barre syndrome (GBS) is an acute immune-mediated
      inflammatory demyelinating disease of the peripheral nervous system,
      characterized by inflammatory cell infiltration. These inflammatory cells,
      including activated macrophages, Th1 cells, and Th17 cells, generally undergo
      metabolic reprogramming and rely mainly on glycolysis to exert functions. This
      study aimed to explore whether enhanced glycolysis contributed to the
      pathogenesis of experimental autoimmune neuritis (EAN), a classic model of GBS.
      METHODS: Preventive and therapeutic treatments with glycolysis inhibitor, 2-deoxy
      D-glucose (2-DG), were applied to EAN rats. The effects of treatments were
      determined by clinical scoring, weighting, and tissue examination. Flow cytometry
      and ELISA were used to evaluate T cell differentiation, autoantibody level, and
      macrophage functions in vivo and in vitro. RESULTS: Glycolysis inhibition with 2
      DG not only inhibited the initiation, but also prevented the progression of EAN,
      evidenced by the improved clinical scores, weight loss, inflammatory cell
      infiltration, and demyelination of sciatic nerves. 2-DG inhibited the
      differentiation of Th1, Th17, and Tfh cells but enhanced Treg cell development,
      accompanied with reduced autoantibody secretion. Further experiments in vitro
      proved glycolysis inhibition decreased the nitric oxide production and
      phagocytosis of macrophages and suppressed the maturation of dendritic cells
      (DC). CONCLUSION: The effects of glycolysis inhibition on both innate and
      adaptive immune responses and the alleviation of animal clinical symptoms
      indicated that enhanced glycolysis contributed to the pathogenesis of EAN.
      Glycolysis inhibition may be a new therapy for GBS.

PMID- 29467009
TI  - Mesalazine-induced myocarditis: a case report.
AB  - BACKGROUND: Myocarditis is a rare complication of therapy with mesalazine, a drug
      widely prescribed in the treatment of inflammatory bowel disease. CASE
      PRESENTATION: We report a case of myocarditis occurring in a 49-year-old British
      man 10 days following initiation of mesalazine therapy for treatment of
      ulcerative colitis. He presented with troponin-positive chest pain, and the
      diagnosis of myocarditis was confirmed on the basis of cardiac magnetic resonance
      imaging, which showed subepicardial delayed gadolinium enhancement in the basal
      to middle inferior and inferolateral segments of the heart. The patient's
      symptoms and condition improved upon stopping mesalazine, and he made a full
      recovery. CONCLUSIONS: Mesalazine-induced myocarditis may be more common than
      first appreciated and is potentially fatal. Therefore, it is imperative that
      clinicians be aware of this potentially life-threatening adverse effect of
      mesalazine therapy and warn patients to seek urgent medical attention if cardiac
      symptoms arise.

PMID- 29467008
TI  - Interventions to prevent hemodynamic instability during renal replacement therapy
      in critically ill patients: a systematic review.
AB  - BACKGROUND: Hemodynamic instability related to renal replacement therapy (HIRRT)
      may increase the risk of death and limit renal recovery. Studies in end-stage
      renal disease populations on maintenance hemodialysis suggest that some renal
      replacement therapy (RRT)-related interventions (e.g., cool dialysate) may reduce
      the occurrence of HIRRT, but less is known about interventions to prevent HIRRT
      in critically ill patients receiving RRT for acute kidney injury (AKI). We sought
      to evaluate the effectiveness of RRT-related interventions for reducing HIRRT in
      such patients across RRT modalities. METHODS: A systematic review of publications
      was undertaken using MEDLINE, MEDLINE in Process, EMBASE, and Cochrane's Central
      Registry for Randomized Controlled Trials (RCTs). Studies that assessed any
      intervention's effect on HIRRT (the primary outcome) in critically ill patients
      with AKI were included. HIRRT was variably defined according to each study's
      definition. Two reviewers independently screened abstracts, identified articles
      for inclusion, extracted data, and evaluated study quality using validated
      assessment tools. RESULTS: Five RCTs and four observational studies were included
      (n = 9; 623 patients in total). Studies were small, and the quality was mostly
      low. Interventions included dialysate sodium modeling (n = 3), ultrafiltration
      profiling (n = 2), blood volume (n = 2) and temperature control (n = 3), duration
      of RRT (n = 1), and slow blood flow rate at initiation (n = 1). Some studies
      applied more than one strategy simultaneously (n = 5). Interventions shown to
      reduce HIRRT from three studies (two RCTs and one observational study) included
      higher dialysate sodium concentration, lower dialysate temperature, variable
      ultrafiltration rates, or a combination of strategies. Interventions not found to
      have an effect included blood volume and temperature control, extended duration
      of intermittent RRT, and slower blood flow rates during continuous RRT
      initiation. How HIRRT was defined and its frequency of occurrence varied widely
      across studies, including those involving the same RRT modality. Pooled analysis
      was not possible due to study heterogeneity. CONCLUSIONS: Small clinical studies
      suggest that higher dialysate sodium, lower temperature, individualized
      ultrafiltration rates, or a combination of these strategies may reduce the risk
      of HIRRT. Overall, for all RRT modalities, there is a paucity of high-quality
      data regarding interventions to reduce the occurrence of HIRRT in critically ill
      patients.

PMID- 29467010
TI  - Human adipose-derived stem cells inhibit bioactivity of keloid fibroblasts.
AB  - BACKGROUND: A keloid is a fibroproliferative disorder occurring in wounds
      characterized by an exaggerated response to injury. To date, no effective cure
      has been identified. As multipotent stem cells, human adipose-derived stem cells
      (ADSCs) may show the possibility for curing diseases such as fibrosis. This study
      sought to explore the potential role of human ADSCs in curing keloids. METHODS:
      After culture in conditioned medium, gene and protein expression of keloid
      fibroblasts was examined using real-time polymerase chain reaction (RT-PCR) and
      Western blotting, while analysis of the cell cycle was used to measure the
      proliferative properties of the cells. Furthermore, ex vivo explant cultures were
      used to test the effects of ADSC-conditioned medium (ADSC-CM) on CD31+ and CD34+
      expression in keloid tissue. RESULTS: Our experimental results show that ADSC-CM
      was able to attenuate extracellular matrix-related gene expression as well as
      decrease protein expression. Cell proliferation was significantly suppressed in
      our study. CD31+ and CD34+ vessels in ex vivo explants were reduced by 55% and
      57% in treatment groups compared with control groups. CONCLUSIONS: Human ADSC-CM
      significantly inhibited keloid fibroblast-related bioactivities.

PMID- 29467011
TI  - Genes sharing the protein family domain decrease the performance of
      classification with RNA-seq genomic signatures.
AB  - BACKGROUND: The experience with running various types of classification on the
      CAMDA neuroblastoma dataset have led us to the conclusion that the results are
      not always obvious and may differ depending on type of analysis and selection of
      genes used for classification. This paper aims in pointing out several factors
      that may influence the downstream machine learning analysis. In particular those
      factors are: type of the primary analysis, type of the classifier and increased
      correlation between the genes sharing a protein domain. They influence the
      analysis directly, but also interplay between them may be important. We have
      compiled the gene-domain database and used it for analysis to see the differences
      between the genes that share a domain versus the rest of the genes in the
      datasets. RESULTS: The major findings are: pairs of genes that share a domain
      have an increased Spearman's correlation coefficients of counts; genes sharing a
      domain are expected to have a lower predictive power due to increased
      correlation. For most of the cases it can be seen with the higher number of
      misclassified samples; classifiers performance may vary depending on a method,
      still in most cases using genes sharing a domain in the training set results in a
      higher misclassification rate; increased correlation in genes sharing a domain
      results most often in worse performance of the classifiers regardless of the
      primary analysis tools used, even if the primary analysis alignment yield varies.
      CONCLUSIONS: The effect of sharing a domain is likely more a results of real
      biological co-expression than just sequence similarity and artifacts of mapping
      and counting. Still, this is more difficult to conclude and needs further
      research. The effect is interesting itself, but we also point out some practical
      aspects in which it may influence the RNA sequencing analysis and RNA biomarker
      use. In particular it means that a gene signature biomarker set build out of RNA
      sequencing results should be depleted for genes sharing common domains. It may
      cause to perform better when applying classification. REVIEWERS: This article was
      reviewed by Dimitar Vassiliev and Susmita Datta.

PMID- 29467012
TI  - Structural and advanced imaging in predicting MGMT promoter methylation of
      primary glioblastoma: a region of interest based analysis.
AB  - BACKGROUND: The methylation status of oxygen 6-methylguanine-DNA
      methyltransferase (MGMT) promoter has been associated with treatment response in
      glioblastoma(GBM). Using pre-operative MRI techniques to predict MGMT promoter
      methylation status remains inconclusive. In this study, we investigated the value
      of features from structural and advanced imagings in predicting the methylation
      of MGMT promoter in primary glioblastoma patients. METHODS: Ninety-two
      pathologically confirmed primary glioblastoma patients underwent preoperative
      structural MR imagings and the efficacy of structural image features were
      qualitatively analyzed using Fisher's exact test. In addition, 77 of the 92
      patients underwent additional advanced MRI scans including diffusion-weighted
      (DWI) and 3-diminsional pseudo-continuous arterial spin labeling (3D pCASL)
      imaging. Apparent diffusion coefficient (ADC) and relative cerebral blood flow
      (rCBF) values within the manually drawn region-of-interest (ROI) were calculated
      and compared using independent sample t test for their efficacies in predicting
      MGMT promoter methylation. Receiver operating characteristic curve (ROC) analysis
      was used to investigate the predicting efficacy with the area under the curve
      (AUC) and cross validations. Multiple-variable logistic regression model was
      employed to evaluate the predicting performance of multiple variables. RESULTS:
      MGMT promoter methylation was associated with tumor location and necrosis (P < 
      0.05). Significantly increased ADC value (P <  0.001) and decreased rCBF (P < 
      0.001) were associated with MGMT promoter methylation in primary glioblastoma.
      The ADC achieved the better predicting efficacy than rCBF (ADC: AUC, 0.860;
      sensitivity, 81.1%; specificity, 82.5%; vs rCBF: AUC, 0.835; sensitivity, 75.0%;
      specificity, 78.4%; P = 0.032). The combination of tumor location, necrosis, ADC
      and rCBF resulted in the highest AUC of 0.914. CONCLUSION: ADC and rCBF are
      promising imaging biomarkers in clinical routine to predict the MGMT promoter
      methylation in primary glioblastoma patients.

PMID- 29467013
TI  - Description of complex interventions: analysis of changes in reporting in
      randomised trials since 2002.
AB  - BACKGROUND: Inadequate description of non-pharmacological complex interventions
      in trial publications means that they cannot be replicated or assessed for
      generalisability. There are published guidelines on how to describe an
      intervention, such as those from the CONSORT Group. However, there have been few
      evaluations of whether intervention reporting is improving. METHODS: We aimed to
      assess whether descriptions of multicomponent, non-pharmacological interventions
      evaluated in randomised trials are improving. To do so, we chose trials of
      educational and psychotherapeutic interventions to promote adherence to therapy,
      and compared those published between 2002 and 2007 (Time-1) with those between
      2010 and 2015 (Time-2). These time periods were chosen to concord with the
      publication in 2008 of the CONSORT extension statement of reporting guidelines
      for non-pharmacological treatment which included items on intervention
      description. We assessed 19 items, based on the CONSORT Statement and the more
      recent Template for Intervention Description and Replication Checklist (TIDieR).
      Two reviewers independently extracted data. We created a quality score of the
      eight items we considered key information for replication and assessment of
      generalisability (setting, provider, recipient, comparator, intervention
      intensity, how it was conducted, existence of a manual or protocol, and detail of
      whether there was an assessment of fidelity). Score per item was '1' if reported
      adequately and '0' if not. RESULTS: Of the eligible trials, 42 were published in
      Time-1 and 134 published in Time-2. The trials included were published in 112
      peer-reviewed journals, 52 of these journals currently require authors to follow
      the CONSORT Statements, while only one recommended adherence to the TIDieR. Most
      items of CONSORT and TIDieR were reported by more than half of the trials at both
      time points. Few trials reported fidelity. A large proportion of the trials did
      not report the existence of a manual or protocol, or what the comparator group
      received. We found no statistically significant improvement in the eight-item
      quality score (Time-1: mean 5.71 (standard deviation (SD) 1.09), Time-2: 5.87 (SD
      1.28), p = 0.49). CONCLUSIONS: We found no overall evidence that reporting the
      specifics of multicomponent, non-pharmacological interventions is improving.
      Details to replicate interventions remain lacking, impairing best implementation
      or meaningful further research. Editorial endorsement of reporting checklists
      needs to be more extensive.

PMID- 29467014
TI  - A biomaterials approach to influence stem cell fate in injectable cell-based
      therapies.
AB  - BACKGROUND: Numerous stem cell therapies use injection-based administration to
      deliver high-density cell preparations. However, cell retention rates as low as
      1% have been observed within days of transplantation. This study investigated the
      effects of varying administration and formulation parameters of injection-based
      administration on cell dose recovery and differentiation fate choice of human
      mesenchymal stem cells. METHODS: The impact of ejection rate via clinically
      relevant Hamilton micro-syringes and biomaterial-assisted delivery was
      investigated. Cell viability, the percentage of cell dose delivered as viable
      cells, proliferation capacity as well as differentiation behaviour in bipotential
      media were assessed. Characterisation of the biomaterial-based cell carriers was
      also carried out. RESULTS: A significant improvement of in-vitro dose recovery in
      cells co-ejected with natural biomaterials was observed, with ejections within 2%
      (w/v) gelatin resulting in 87.5 +/- 14% of the cell dose being delivered as
      viable cells, compared to 32.2 +/- 19% of the dose ejected in the commonly used
      saline vehicle at 10 MUl/min. Improvement in cell recovery was not associated
      with the rheological properties of biomaterials utilised, as suggested by
      previous studies. The extent of osteogenic differentiation was shown to be
      substantially altered by choice of ejection rate and cell carrier, despite
      limited contact time with cells during ejection. Collagen type I and bone-derived
      extracellular matrix cell carriers yielded significant increases in mineralised
      matrix deposited at day 21 relative to PBS. CONCLUSIONS: An enhanced
      understanding of how administration protocols and biomaterials influence cell
      recovery, differentiation capacity and choice of fate will facilitate the
      development of improved administration and formulation approaches to achieve
      higher efficacy in stem cell transplantation.

PMID- 29467015
TI  - Prevention of disease progression in Leishmania infantum-infected dogs with
      dietary nucleotides and active hexose correlated compound.
AB  - BACKGROUND: The prevalence of Leishmania infantum infection in clinically healthy
      dogs can be several times higher than that of clinical disease in endemic areas.
      Although treatment is not recommended in dogs with subclinical infection, these
      animals should be managed to prevent disease progression and parasite
      transmission to human beings or to other dogs. Dietary nucleotides and active
      hexose correlated compound (AHCC) have been shown to modulate the immune
      response. A recent study in dogs with clinical leishmaniosis receiving an initial
      28-day course of methylglucamine antimoniate showed that six-month administration
      of a dietary supplement containing nucleotides plus AHCC achieves similar
      efficacy to allopurinol. Since the type of immune response plays a key role in
      the evolution of patients with leishmaniosis, the present study was aimed at
      evaluating the preventive effect of this supplement in avoiding or delaying
      disease progression in clinically healthy Leishmania-infected dogs. METHODS:
      Forty-six dogs were included in this multicenter, randomized, double-blind,
      placebo-controlled trial. Dogs received once-daily oral administration of a
      placebo or a dietary supplement containing nucleotides plus AHCC. Disease
      progression was monitored throughout the study in both groups. At 0, 60, 180 and
      365 days of treatment, clinical signs were evaluated using a validated clinical
      scoring system, and several analytes were measured from blood, urine, and bone
      marrow samples. RESULTS: During the study, a significantly lower (P = 0.047)
      proportion of dogs changed their clinical status and became sick in the
      supplement group (3/20; 15%), compared to the placebo group (10/22; 45.5%). ELISA
      determined antibody titers were significantly reduced compared to baseline at all
      time points with the supplement (P < 0.01), but not with the placebo. The mean
      clinical score of disease severity was significantly lower in the supplement
      group after 180 days (P = 0.014). No significant differences were observed for
      the other parameters. The dietary supplement was well tolerated. CONCLUSIONS:
      Oral administration of nucleotides plus AHCC for 365 days in clinically healthy
      L. infantum-infected dogs is safe, allows a significant reduction in anti
      Leishmania antibodies, and leads to a lower disease progression rate, hence
      exerting a preventive effect.

PMID- 29467016
TI  - Advancing osteochondral tissue engineering: bone morphogenetic protein,
      transforming growth factor, and fibroblast growth factor signaling drive ordered
      differentiation of periosteal cells resulting in stable cartilage and bone
      formation in vivo.
AB  - BACKGROUND: Chondrogenic mesenchymal stem cells (MSCs) have not yet been used to
      address the clinical demands of large osteochondral joint surface defects. In
      this study, self-assembling tissue intermediates (TIs) derived from human
      periosteum-derived stem/progenitor cells (hPDCs) were generated and validated for
      stable cartilage formation in vivo using two different animal models. METHODS:
      hPDCs were aggregated and cultured in the presence of a novel growth factor (GF)
      cocktail comprising of transforming growth factor (TGF)-beta1, bone morphogenetic
      protein (BMP)2, growth differentiation factor (GDF)5, BMP6, and fibroblast growth
      factor (FGF)2. Quantitative polymerase chain reaction (PCR) and
      immunohistochemistry were used to study in vitro differentiation. Aggregates were
      then implanted ectopically in nude mice and orthotopically in critical-size
      osteochondral defects in nude rats and evaluated by microcomputed tomography
      (uCT) and immunohistochemistry. RESULTS: Gene expression analysis after 28 days
      of in vitro culture revealed the expression of early and late chondrogenic
      markers and a significant upregulation of NOGGIN as compared to human articular
      chondrocytes (hACs). Histological examination revealed a bilayered structure
      comprising of chondrocytes at different stages of maturity. Ectopically, TIs
      generated both bone and mineralized cartilage at 8 weeks after implantation.
      Osteochondral defects treated with TIs displayed glycosaminoglycan (GAG)
      production, type-II collagen, and lubricin expression. Immunostaining for human
      nuclei protein suggested that hPDCs contributed to both subchondral bone and
      articular cartilage repair. CONCLUSION: Our data indicate that in vitro derived
      osteochondral-like tissues can be generated from hPDCs, which are capable of
      producing bone and cartilage ectopically and behave orthotopically as
      osteochondral units.

PMID- 29467017
TI  - ADJunctive Ulinastatin in Sepsis Treatment in China (ADJUST study): study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Sepsis is a major challenge in critical care and is associated with
      high mortality. Current management of sepsis and septic shock remains mainly
      supportive. Both basic and clinical research has shown that ulinastatin can
      improve the prognosis of sepsis. The aim of this trial is to evaluate the
      efficacy and safety profiles of ulinastatin compared with placebo.
      METHODS/DESIGN: In this multi-center, double-blind, randomized placebo-controlled
      trial we are recruiting a total of 348 subjects meeting "The Third International
      Consensus Definitions for Sepsis and Septic Shock" (Sepsis-3). Subjects will be
      randomized (1:1) to receive ulinastatin 400,000 IU three times a day for 10 days
      or matching placebo and usual care simultaneously. The primary outcome is 28-day
      all-cause mortality. Adverse events and serious adverse events will be monitored
      closely. DISCUSSION: ADJUST is a large, multi-center, double-blind, randomized,
      parallel-group, placebo-controlled trial of ulinastatin in mainland China and is
      well-designed on the basis of previous studies. The results of this trial may
      help to provide evidence-based recommendations for treatment of sepsis. TRIAL
      REGISTRATION: ClinicalTrials.gov, ID: NCT02647554 . First registered on 27
      December 2015, and last verified in December of 2016. Protocol version: 2.1,
      verified on 19 July 2016.

PMID- 29467018
TI  - Efficacy of different DNA and MVA prime-boost vaccination regimens against a Rift
      Valley fever virus (RVFV) challenge in sheep 12 weeks following vaccination.
AB  - The aim of this work was to evaluate the immunogenicity and efficacy of DNA and
      MVA vaccines encoding the RVFV glycoproteins Gn and Gc in an ovine model of RVFV
      infection. Adult sheep of both sexes were challenged 12 weeks after the last
      immunization and clinical, virological, biochemical and immunological
      consequences, were analyzed. Strategies based on immunization with homologous DNA
      or heterologous DNA/MVA prime-boost were able to induce a rapid in vitro
      neutralizing antibody response as well as IFNgamma production after in vitro
      virus specific re-stimulation. In these animals we observed reduced viremia
      levels and less clinical signs when compared with mock-immunized controls. In
      contrast, sheep inoculated with a homologous MVA prime-boost showed increased
      viremia correlating with the absence of detectable neutralizing antibody
      responses, despite of inducing cellular responses after the last immunization.
      However, faster induction of neutralizing antibodies and IFNgamma production
      after challenge were found in this group when compared to the mock vaccinated
      group, indicative of a primed immune response. In conclusion, these results
      suggest that vaccination strategies based on DNA priming were able to mount and
      maintain specific anti-RVFV glycoprotein immune responses upon homologous or
      heterologous booster doses, warranting further optimization in large animal
      models of infection.

PMID- 29467020
TI  - Insulin-like growth factor-1-mediated regulation of miR-193a expression promotes
      the migration and proliferation of c-kit-positive mouse cardiac stem cells.
AB  - BACKGROUND: C-kit-positive cardiac stem cells (CSCs) have been shown to be a
      promising candidate treatment for myocardial infarction and heart failure.
      Insulin-like growth factor (IGF)-1 is an anabolic growth hormone that regulates
      cellular proliferation, differentiation, senescence, and death in various
      tissues. Although IGF-1 promotes the migration and proliferation of c-kit
      positive mouse CSCs, the underlying mechanism remains unclear. METHODS: Cells
      were isolated from adult mouse hearts, and c-kit-positive CSCs were separated
      using magnetic beads. The cells were cultured with or without IGF-1, and c-kit
      expression was measured by Western blotting. IGF-1 induced CSC proliferation and
      migration, as measured through Cell Counting Kit-8 (CCK-8) and Transwell assays,
      respectively. The miR-193a expression was measured by quantitative real-time PCR
      (qPCR) assays. RESULTS: IGF-1 enhanced c-kit expression in c-kit-positive CSCs.
      The activities of the phosphoinositol 3-kinase (PI3K)/AKT signaling pathway and
      DNA methyltransferases (DNMTs) were enhanced, and their respective inhibitors
      LY294002 and 5-azacytidine (5-AZA) blunted c-kit expression. Based on the results
      of quantitative real-time PCR (qPCR) assays, the expression of miR-193a, which is
      embedded in a CpG island, was down-regulated in the IGF-1-stimulated group and
      negatively correlated with c-kit expression, whereas c-kit-positive CSCs infected
      with lentivirus carrying micro-RNA193a displayed reduced c-kit expression,
      migration and proliferation. CONCLUSIONS: IGF-1 upregulated c-kit expression in c
      kit-positive CSCs resulting in enhanced CSC proliferation and migration by
      activating the PI3K/AKT/DNMT signaling pathway to epigenetically silence miR
      193a, which negatively modifies the c-kit expression level.

PMID- 29467019
TI  - Clinical- and cost-effectiveness of the STAR care pathway compared to usual care
      for patients with chronic pain after total knee replacement: study protocol for a
      UK randomised controlled trial.
AB  - BACKGROUND: Approximately 20% of patients experience chronic pain after total
      knee replacement. There is little evidence for effective interventions for the
      management of this pain, and current healthcare provision is patchy and
      inconsistent. Given the complexity of this condition, multimodal and
      individualised interventions matched to pain characteristics are needed. We have
      undertaken a comprehensive programme of work to develop a care pathway for
      patients with chronic pain after total knee replacement. This protocol describes
      the design of a randomised controlled trial to evaluate the clinical- and cost
      effectiveness of a complex intervention care pathway compared with usual care.
      METHODS: This is a pragmatic two-armed, open, multi-centred randomised controlled
      trial conducted within secondary care in the UK. Patients will be screened at 2
      months after total knee replacement and 381 patients with chronic pain at 3
      months postoperatively will be recruited. Recruitment processes will be optimised
      through qualitative research during a 6-month internal pilot phase. Patients are
      randomised using a 2:1 intervention:control allocation ratio. All participants
      receive usual care as provided by their hospital. The intervention comprises an
      assessment clinic appointment at 3 months postoperatively with an Extended Scope
      Practitioner and up to six telephone follow-up calls over 12 months. In the
      assessment clinic, a standardised protocol is followed to identify potential
      underlying causes for the chronic pain and enable appropriate onward referrals to
      existing services for targeted and individualised treatment. Outcomes are
      assessed by questionnaires at 6 and 12 months after randomisation. The co-primary
      outcomes are pain severity and pain interference assessed using the Brief Pain
      Inventory at 12 months after randomisation. Secondary outcomes relate to resource
      use, function, neuropathic pain, mental well-being, use of pain medications,
      satisfaction with pain relief, pain frequency, capability, health-related quality
      of life and bodily pain. After trial completion, up to 30 patients in the
      intervention group will be interviewed about their experiences of the care
      pathway. DISCUSSION: If shown to be clinically and cost-effective, this care
      pathway intervention could improve the management of chronic pain after total
      knee replacement. TRIAL REGISTRATION: ISRCTN registry ( ISRCTN92545361 ),
      prospectively registered on 30 August 2016.

PMID- 29467021
TI  - Conjunctival transcriptome profiling of Solomon Islanders with active trachoma in
      the absence of Chlamydia trachomatis infection.
AB  - BACKGROUND: Clinical signs of active (inflammatory) trachoma are found in many
      children in the Solomon Islands, but the majority of these individuals have no
      serological evidence of previous infection with Chlamydia trachomatis. In Temotu
      and Rennell and Bellona provinces, ocular infections with C. trachomatis were
      seldom detected among children with active trachoma; a similar lack of
      association was seen between active trachoma and other common bacterial and viral
      causes of follicular conjunctivitis. Here, we set out to characterise patterns of
      gene expression at the conjunctivae of children in these provinces with and
      without clinical signs of trachomatous inflammation-follicular (TF) and C.
      trachomatis infection. METHODS: Purified RNA from children with and without
      active trachoma was run on Affymetrix GeneChip Human Transcriptome Array 2.0
      microarrays. Profiles were compared between individuals with ocular C.
      trachomatis infection and TF (group DI; n = 6), individuals with TF but no C.
      trachomatis infection (group D; n = 7), and individuals without TF or C.
      trachomatis infection (group N; n = 7). Differential gene expression and gene set
      enrichment for pathway membership were assessed. RESULTS: Conjunctival gene
      expression profiles were more similar within-group than between-group. Principal
      components analysis indicated that the first and second principal components
      combined explained almost 50% of the variance in the dataset. When comparing the
      DI group to the N group, genes involved in T-cell proliferation, B-cell
      signalling and CD8+ T cell signalling pathways were differentially regulated.
      When comparing the DI group to the D group, CD8+ T-cell regulation, interferon
      gamma and IL17 production pathways were enriched. Genes involved in RNA
      transcription and translation pathways were upregulated when comparing the D
      group to the N group. CONCLUSIONS: Gene expression profiles in children in the
      Solomon Islands indicate immune responses consistent with bacterial infection
      when TF and C. trachomatis infection are concurrent. The transcriptomes of
      children with TF but without identified infection were not consistent with
      allergic or viral conjunctivitis.

PMID- 29467022
TI  - Recovery of muscle function after deep neuromuscular block by means of diaphragm
      ultrasonography and adductor of pollicis acceleromyography with comparison of
      neostigmine vs. sugammadex as reversal drugs: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: The extensive use of neuromuscular blocking agents (NMBAs) during
      surgical procedures still leads to potential residual paralyzing effects in the
      postoperative period. Indeed, neuromuscular monitoring in an intra-operative
      setting is strongly advocated. Acetylcholinesterase inhibitors can reverse muscle
      block, but their short half-life may lead to residual curarization in the ward,
      especially when intermediate or long-acting NMBAs have been administered.
      Sugammadex is the first selective reversal drug for steroidal NMBAs; it has been
      shown to give full and rapid recovery of muscle strength, thus minimizing the
      occurrence of residual curarization. Acceleromyography of the adductor pollicis
      is the gold standard for detecting residual curarization, but it cannot be
      carried out on conscious patients. Ultrasonography of diaphragm thickness may
      reveal residual effects of NMBAs in conscious patients. METHODS/DESIGN: This
      prospective, double-blind, single-center randomized controlled study will enroll
      patients (of American Society of Anesthesiologists physical status I-II, aged 18
      80 years) who will be scheduled to undergo deep neuromuscular block with
      rocuronium for ear, nose, or throat surgery. The study's primary objective will
      be to compare the effects of neostigmine and sugammadex on postoperative residual
      curarization using two different tools: diaphragm ultrasonography and
      acceleromyography of the adductor pollicis. Patients will be extubated when the
      train-of-four ratio is > 0.9. Diaphragm ultrasonography will be used to evaluate
      the thickening fraction, which is the difference between the end expiratory
      thickness and the end inspiratory thickness, normalized to the end expiratory
      thickness. Ultrasonography will be performed before the initiation of general
      anesthesia, before extubation, and 10 and 30 min after discharging patients from
      the operating room. The secondary objective will be to compare the incidence of
      postoperative complications due to residual neuromuscular block between patients
      who receive neostigmine and those who receive sugammadex. DISCUSSION:
      Postoperative residual curarization is a topic of paramount importance, because
      its occurrence can cause complications and increase the length of stay in
      hospital and the related costs. Diaphragm ultrasound assessment may become a
      bedside integrative tool in the neuromuscular monitoring field to detect
      concealed residual curarization in surgical patients who have received paralyzing
      agents. TRIAL REGISTRATION: EudraCT, 2013-004787-62. Registered on 18 June 2014,
      as "Evaluation of muscle function recovery after deep neuromuscular blockade by
      acceleromyography of the adductor pollicis or diaphragmatic echography:
      comparison between sugammadex and neostigmine." ClinicalTrials.gov, NCT02698969 .
      Registered on 15 February 2016, as "Recovery of Muscle Function After Deep
      Neuromuscular Block by Means of Diaphragm Ultrasonography and Adductor Pollicis
      Acceleromyography: Comparison of Neostigmine vs. Sugammadex as Reversal Drugs."

PMID- 29467023
TI  - Protracted immune disorders at one year after ICU discharge in patients with
      septic shock.
AB  - BACKGROUND: Sepsis is a leading cause of mortality and critical illness worldwide
      and is associated with an increased mortality rate in the months following
      hospital discharge. The occurrence of persistent or new organ dysfunction(s)
      after septic shock raises questions about the mechanisms involved in the post
      sepsis status. The present study aimed to explore the immune profiles of patients
      one year after being discharged from the intensive care unit (ICU) following
      treatment for abdominal septic shock. METHODS: We conducted a prospective, single
      center, observational study in the surgical ICU of a university hospital. Eighty
      six consecutive patients admitted for septic shock of abdominal origin were
      included in this study. Fifteen different plasma biomarkers were measured at ICU
      admission, at ICU discharge and at one year after ICU discharge. Three different
      clusters of biomarkers were distinguished according to their functions, namely:
      (1) inflammatory response, (2) cell damage and apoptosis, (3) immunosuppression
      and resolution of inflammation. The primary objective was to characterize
      variations in the immune status of septic shock patients admitted to ICU up to
      one year after ICU discharge. The secondary objective was to evaluate the
      relationship between these biomarker variations and patient outcomes. RESULTS: At
      the onset of septic shock, we observed a cohesive pro-inflammatory profile and
      low levels of inflammation resolution markers. At ICU discharge, the immune
      status demonstrated decreased but persistent inflammation and increased
      immunosuppression, with elevated programmed cell death protein-1 (PD-1) levels,
      and a counterbalanced resolution process, with elevated levels of interleukin-10
      (IL-10), resolvin D5 (RvD5), and IL-7. One year after hospital discharge,
      homeostasis was not completely restored with several markers of inflammation
      remaining elevated. Remarkably, IL-7 was persistently elevated, with levels
      comparable to those observed after ICU discharge, and PD-1, while lower, remained
      in the elevated abnormal range. CONCLUSIONS: In this study, protracted immune
      disturbances were observed one year after ICU discharge. The study results
      suggested the presence of long-lasting immune illness disorders following a long
      term septic insult, indicating the need for long-term patient follow up after ICU
      discharge and questioning the use of immune intervention to restore immune
      homeostasis after abdominal septic shock.

PMID- 29467024
TI  - Male synthetic sling versus artificial urinary sphincter trial for men with
      urodynamic stress incontinence after prostate surgery (MASTER): study protocol
      for a randomised controlled trial.
AB  - BACKGROUND: Stress urinary incontinence (SUI) is a frequent adverse effect for
      men undergoing prostate surgery. A large proportion (around 8% after radical
      prostatectomy and 2% after transurethral resection of prostate (TURP)) are left
      with severe disabling incontinence which adversely effects their quality of life
      and many are reliant on containment measures such as pads (27% and 6%
      respectively). Surgery is currently the only option for active management of the
      problem. The overwhelming majority of surgeries for persistent bothersome SUI
      involve artificial urinary sphincter (AUS) insertion. However, this is expensive,
      and necessitates manipulation of a pump to enable voiding. More recently, an
      alternative to AUS has been developed - a synthetic sling for men which elevates
      the urethra, thus treating SUI. This is thought, by some, to be less invasive,
      more acceptable and less expensive than AUS but clear evidence for this is
      lacking. The MASTER trial aims to determine whether the male synthetic sling is
      non-inferior to implantation of the AUS for men who have SUI after prostate
      surgery (for cancer or benign disease), judged primarily on clinical
      effectiveness but also considering relative harms and cost-effectiveness.
      METHODS/DESIGN: Men with urodynamic stress incontinence (USI) after prostate
      surgery, for whom surgery is judged appropriate, are the target population. We
      aim to recruit men from secondary care urological centres in the UK NHS who carry
      out surgery for post-prostatectomy incontinence. Outcomes will be assessed by
      participant-completed questionnaires and 3-day urinary bladder diaries at
      baseline, 6, 12 and 24 months. The 24-h urinary pad test will be used at baseline
      as an objective assessment of urine loss. Clinical data will be completed at the
      time of surgery to provide details of the operative procedures, complications and
      resource use in hospital. At 12 months, men will also have a clinical review to
      evaluate the results of surgery (including another 24-h pad test) and to identify
      problems or need for further treatment. DISCUSSION: A robust examination of the
      comparative effectiveness of the male synthetic sling will provide high-quality
      evidence to determine whether or not it should be adopted widely in the NHS.
      TRIAL REGISTRATION: International Standard Randomised Controlled Trial Registry:
      Number ISRCTN49212975 . Registered on 22 July 2013. First patient randomised on
      29 January 2014.

PMID- 29467025
TI  - Controlling Hypertension After Severe Cerebrovascular Event (CHASE): study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: No ideal blood pressure (BP) range has been scientifically determined
      for acute stroke, and no studies on BP management have been carried out for
      patients with severe stroke. This trial aims to investigate whether
      individualized lowering of elevated BP would improve the outcome in patients with
      severe stroke. METHODS/DESIGN: The CHASE trial is a multicenter, randomized,
      controlled study. A total of 500 adult patients with acute severe stroke will be
      enrolled in 18 study sites in China and randomized to individualized BP lowering
      (10-15% reduction from admission level) or guideline-recommended BP lowering. The
      primary outcome measurement is the proportion of participants with a poor outcome
      (modified Rankin Scale >= 3) at day 90 of enrollment. Secondary outcomes include
      disability at hospital discharge and the ability of activities of daily living at
      day 90 of enrollment. The relationship between intervention and the primary
      outcome will be analyzed using multivariate logistic regression adjusted for
      study site, demographics, and baseline characteristics. DISCUSSION: The CHASE
      trial will be the first study to explore the optimum BP management for acute
      severe stroke. This trial potentially offers a strong argument for individualized
      target for lowering elevated BP in patients with severe stroke. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT02982655 . Registered on 30 November 2016.

PMID- 29467026
TI  - What is new in critical care echocardiography?

PMID- 29467027
TI  - Quality of reporting of outcomes in phase III studies of pulmonary tuberculosis:
      a systematic review.
AB  - BACKGROUND: Despite more than 60 years of clinical trials, tuberculosis (TB)
      still causes a high global burden of mortality and morbidity. Treatment currently
      requires multiple drugs in combination, taken over a prolonged period. New drugs
      are needed to shorten treatment duration, prevent resistance and reduce adverse
      events. However, to improve on current methodology in drug development, a more
      complete understanding of the existing clinical evidence base is required.
      METHODS: A systematic review was undertaken to summarise outcomes reported in
      phase III trials of patients with newly diagnosed pulmonary TB. A systematic
      search of databases (PubMed, MEDLINE, EMBASE, CENTRAL and LILACs) was conducted
      on 30 November 2017 to retrieve relevant peer-reviewed articles. Reference lists
      of included studies were also searched. This systematic review considered all
      reported outcomes. RESULTS: Of 248 included studies, 229 considered "on
      treatment" outcomes whilst 148 reported "off-treatment" outcomes. There was wide
      variation and ambiguity in the definition of reported outcomes, including their
      relationship to treatment and in the time points evaluated. Additional challenges
      were observed regarding the analysis approach taken (per protocol versus
      intention to treat) and the varying durations of "intensive" and "continuation"
      phases of treatment. Bacteriological outcomes were most frequently reported but
      radiological and clinical data were often included as an implicit or explicit
      component of the overall definition of outcome. CONCLUSIONS: Terminology used to
      define long-term outcomes in phase III trials is inconsistent, reflecting
      evolving differences in protocols and practices. For successful future cumulative
      meta-analysis, the findings of this review suggest that greater availability of
      individual patient data and the development of a core outcome set would be
      desirable. In the meantime, we propose a simple and logical approach which should
      facilitate combination of key evidence and inform improvements in the methodology
      of TB drug development and clinical trials.

PMID- 29467028
TI  - Diurnal variation of NMDA receptor expression in the rat cerebral cortex is
      associated with traumatic brain injury damage.
AB  - OBJECTIVE: Data from our laboratory suggest that recovery from a traumatic brain
      injury depends on the time of day at which it occurred. In this study, we
      examined whether traumatic brain injury -induced damage is related to circadian
      variation in N-methyl-D-aspartate receptor expression in rat cortex. RESULTS: We
      confirmed that traumatic brain injury recovery depended on the time of day at
      which the damage occurred. We also found that motor cortex N-methyl-D-aspartate
      receptor subunit NR1 expression exhibited diurnal variation in both control and
      traumatic brain injury-subjected rats. However, this rhythm is more pronounced in
      traumatic brain injury-subjected rats, with minimum expression in those injured
      during nighttime hours. These findings suggest that traumatic brain injury
      occurrence times should be considered in future clinical studies and when
      designing neuroprotective strategies for patients.

PMID- 29467029
TI  - A newly developed oxime K203 is the most effective reactivator of tabun-inhibited
      acetylcholinesterase.
AB  - BACKGROUND: Based on in vitro and in vivo rat experiments, the newly developed
      acetylcholinesterase (AChE) reactivator, K203, appears to be much more effective
      in the treatment of tabun poisonings than currently fielded oximes. METHODS: To
      determine if this reactivating efficacy would extend to humans, studies were
      conducted in vitro using human brain homogenate as the source of AChE. The
      efficacy of K203 was compared with commercially available oximes; pralidoxime,
      obidoxime and asoxime (HI-6). RESULTS: Reactivation studies showed that K203 was
      the most effective reactivator with a second order kinetic constant (kr) of 2142
      min- 1. M- 1, which was 51 times higher than that obtained for obidoxime (kr = 42
      min- 1. M- 1). Both pralidoxime and asoxime (HI-6) failed to significantly
      reactivate tabun-inhibited human AChE. DISCUSSION: According to these results and
      previous studies, using K203, it appears that oxime K203 is the most effective
      reactivator of tabun-inhibited cholinesterase in several species including humans
      and should be considered as a possible medical countermeasure to tabun exposure.

PMID- 29467030
TI  - Drug discontinuation before contrast procedures and the effect on acute kidney
      injury and other clinical outcomes: a systematic review protocol.
AB  - BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is defined as worsening
      of renal function after the administration of iodinated contrast material. In
      patients with cardiovascular disease, kidney disease, and/or diabetes, renin
      angiotensin system blockers, non-steroidal anti-inflammatory drugs, diuretics,
      and metformin can increase the risk of CI-AKI when undergoing contrast imaging.
      Despite CI-AKI being the leading iatrogenic cause of acute kidney injury, there
      is a lack of sufficient scientific evidence supporting which drugs should be
      stopped, when they should be stopped, and when they should be resumed. The
      purpose of this systematic review is to assess (1) the effect of withholding
      medication before contrast procedures on the risk of CI-AKI and other clinical
      outcomes and (2) the incidence of adverse events occurring after withholding
      these drugs prior to contrast procedures. This protocol has been registered with
      PROSPERO,
      https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016033178 .
      METHODS: An information specialist will assist in searching MEDLINE, Embase, and
      the Cochrane Library databases to identify randomized controlled trials,
      observational studies, case reports, and case series. Relevant abstracts from
      professional society meetings and web-based registries of clinical trials will
      also be included. Studies included will compare patients aged >= 18 years
      instructed to continue taking the drugs of interest and those advised to stop
      taking them before undergoing contrast procedures. If these drugs are not
      withheld prior to contrast procedures, the studies must compare patients who are
      administered these drugs and those who are not before undergoing contrast
      procedures. Two reviewers will independently screen the titles and abstracts of
      the studies obtained from the search using pre-defined inclusion criteria and
      will then extract data from the full texts of selected studies. The quality of
      the studies will be assessed by two independent reviewers using the Cochrane Risk
      of Bias 2.0 tool for randomized trials and the Newcastle-Ottawa Scale for
      observational studies. DISCUSSION: This systematic review will provide a
      synthesis of current evidence on the discontinuation of drugs prior to contrast
      procedures and its effect on CI-AKI and other clinical outcomes. These findings
      will provide clinicians with guidelines and serve as a strong research base for
      future studies in this field. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42016033178.

PMID- 29467031
TI  - Assessment of communication technology and post-operative telephone surveillance
      during global urology mission.
AB  - OBJECTIVE: Compliance with post-operative follow-up in the context of
      international surgical trips is often poor. The etiology of this problem is
      multifactorial and includes lack of local physician involvement, transportation
      costs, and work responsibilities. We aimed to better understand availability of
      communication technologies within Belize and use this information to improve
      follow-up after visiting surgical trips to a public hospital in Belize City.
      Accordingly, a 6-item questionnaire assessing access to communication
      technologies was completed by all patients undergoing evaluation by a visiting
      surgical team in 2014. Based on this data, a pilot program for patients
      undergoing surgery was instituted for subsequent missions (2015-2016) that
      included a 6-week post-operative telephone interview with a visiting physician
      located in the United States. RESULTS: Fifty-four (n = 54) patients were assessed
      via survey with 89% responding that they had a mobile phone. Patients reported
      less access to home internet (59%), local internet (52%), and email (48%). Of 35
      surgical patients undergoing surgery during 2 subsequent surgical trips, 18 (51%)
      were compliant with telephone interview at 6-week follow-up. Issues were
      identified in 3 (17%) patients that allowed for physician assistance. The cost
      per patient interview was $10 USD.

PMID- 29467032
TI  - Pegylated and liposomal doxorubicin is associated with high mortality and causes
      limited cardiotoxicity in mice.
AB  - OBJECTIVE: We wanted to determine the impact of different doses of a pegylated
      and liposomal formulation of the cardiotoxic drug doxorubicin on cardiac
      function, fibrosis and survival in mice. The drug causes myocardial damage by
      producing reactive oxygen species, mitochondrial damage and lipid peroxidation.
      Thymosin beta 4 is a peptide with cardioprotective, anti-oxidant and anti
      fibrotic properties and we further investigated whether the peptide could
      attenuate this drug-induced injury by measuring cardiac function and fibrosis.
      RESULTS: Mice receiving high doses of doxorubicin died early during follow-up.
      Lowering the dose improved survival but did not markedly impair cardiac function
      on echocardiography and caused only limited fibrosis on histology. Thymosin beta
      4 had only a mild protective effect on early cardiac function and did not
      significantly influence myocardial fibrosis. In conclusion, the use of pegylated
      and liposomal doxorubicin was not appropriate for inducing experimental
      cardiomyopathy. Thymosin beta 4 therapy was not beneficial in this setting.

PMID- 29467033
TI  - Correction to: Testing the effectiveness of a motivational interviewing-based
      brief intervention for substance use as an adjunct to usual care in community
      based AIDS service organizations: study protocol for a multisite randomized
      controlled trial.
AB  - Upon publication of the original article.

PMID- 29467034
TI  - Seasonal differences in brown adipose tissue density and pulse rate variability
      in a thermoneutral environment.
AB  - BACKGROUND: Brown adipose tissue (BAT) is sympathetically activated and induces
      thermogenesis during cold exposure, thereby influencing energy expenditure and
      body fat levels. The very low frequency (VLF) components of pulse rate
      variability could be a form of thermogenic sympathetic nervous activity, but no
      clear relationship has yet been reported between VLF activity and BAT density. We
      therefore aimed to evaluate the association between them. METHODS: We enrolled 20
      adults in winter and 20 matched adults in summer. We assessed BAT densities based
      on total hemoglobin concentrations ([total-Hb]) measured with near-infrared time
      resolved spectroscopy. We calculated VLF activity from pulse rate variability
      measurements. RESULTS: BAT density ([total-Hb]; winter 70.5 +/- 17.0 MUM, summer
      57.8 +/- 18.3 MUM) and VLF activity (winter 6.7 +/- 0.8, summer 6.1 +/- 0.9) were
      significantly higher in winter than in summer (P < 0.05). However, there was no
      significant correlation between VLF activity and BAT density in either season.
      CONCLUSION: Each parameter exhibited seasonal variation, but we failed to observe
      any significant correlations.

PMID- 29467035
TI  - Prevalence and psychometric screening for the detection of major depressive
      disorder and post-traumatic stress disorder in adults injured in a motor vehicle
      crash who are engaged in compensation.
AB  - BACKGROUND: Physical injury and psychological disorder following a motor vehicle
      crash (MVC) is a public health concern. The objective of this research was to
      determine rates of major depressive disorder (MDD) and post-traumatic stress
      disorder (PTSD) in adults with MVC-related injury engaged in compensation, and to
      determine the capacity (e.g. sensitivity and specificity) of two psychometric
      scales for estimating the presence of MDD and PTSD. METHODS: Participants
      included 109 adults with MVC-related injury engaged in compensation during 2015
      to 2017, in Sydney, Australia. The mean time from MVC to baseline assessment was
      11 weeks. Comprehensive assessment was conducted at baseline, and the Depression
      Anxiety Stress Scales (DASS-21) and the Impact of Event Scale-Revised (IES-R)
      were administered to determine probable MDD and PTSD. An online psychiatric
      interview, based on Diagnostic and Statistical Manual for Mental Disorders (DSM
      5), was used to diagnose actual MDD and PTSD, acknowledged as gold standard
      diagnostic criteria. One-way multivariate analyses of variance established
      criterion validity of the DASS-21 and IES-R, and sensitivity and specificity
      analyses were conducted to determine the most sensitive cut-off points for
      detecting probable MDD and PTSD. RESULTS: Substantial rates of MDD (53.2%) and
      PTSD (19.3%) were found. The DASS-21 and IES-R were shown to have excellent
      criterion validity for detecting MDD and PTSD in injured participants. A range of
      cut-off points were investigated and shown to have acceptable sensitivity and
      specificity for detecting MDD and PTSD in an injured population engaged in
      compensation. The preferred cut-off points based on this study are: to detect
      MDD, a DASS-21 total score of 30 and/or a DASS-21 depression score of 10; to
      detect PTSD, IES-R scores of 33-40 and/or a DASS-21 anxiety score of 7-8.
      CONCLUSIONS: Major psychological disorder is prevalent following a MVC. Results
      suggest the DASS-21 and IES-R are suitable for use in clinical/compensation
      settings to detect probable MDD and PTSD soon after a MVC in physically injured
      people engaged in compensation. These results provide positive direction in the
      public health arena for improving mental health outcomes. TRIAL REGISTRATION:
      Clinical Trials registration number: ANZCTR - ACTRN12615000326594 (9th April
      2015).

PMID- 29467037
TI  - Strategies for successful trauma registry implementation in low- and middle
      income countries-protocol for a systematic review.
AB  - BACKGROUND: The benefits of trauma registries have been well described. The
      crucial data they provide may guide injury prevention strategies, inform resource
      allocation, and support advocacy and policy. This has been shown to reduce trauma
      related mortality in various settings. Trauma remains a leading cause of
      mortality in low- and middle-income countries (LMICs). However, the
      implementation of trauma registries in LMICs can be challenging due to lack of
      funding, specialized personnel, and infrastructure. This study explores
      strategies for successful trauma registry implementation in LMICs. METHODS: The
      protocol was registered a priori (CRD42017058586). A peer-reviewed search
      strategy of multiple databases will be developed with a senior librarian. As per
      PRISMA guidelines, first screen of references based on abstract and title and
      subsequent full-text review will be conducted by two independent reviewers.
      Disagreements that cannot be resolved by discussion between reviewers shall be
      arbitrated by the principal investigator. Data extraction will be performed using
      a pre-defined data extraction sheet. Finally, bibliographies of included articles
      will be hand-searched. Studies of any design will be included if they describe or
      review development and implementation of a trauma registry in LMICs. No language
      or period restrictions will be applied. Summary statistics and qualitative meta
      narrative analyses will be performed. DISCUSSION: The significant burden of
      trauma in LMIC environments presents unique challenges and limitations. Adapted
      strategies for deployment and maintenance of sustainable trauma registries are
      needed. Our methodology will systematically identify recommendations and
      strategies for successful trauma registry implementation in LMICs and describe
      threats and barriers to this endeavor. SYSTEMATIC REVIEW REGISTRATION: The
      protocol was registered on the PROSPERO international prospective register of
      systematic reviews ( CRD42017058586 ).

PMID- 29467036
TI  - The living dead? Perception of persons in the unresponsive wakefulness syndrome
      in Germany compared to the USA.
AB  - BACKGROUND: The extent to which people ascribe mind to others has been shown to
      predict the extent to which human rights are conferred. Therefore, in the context
      of disorders of consciousness (DOC), mind ascription can influence end of life
      decisions. A previous US-American study indicated that participants ascribed even
      less mind to patients with unresponsive-wakefulness-syndrome (UWS) than to the
      dead. Results were explained in terms of implicit dualism and religious beliefs,
      as highly religious people ascribed least mind to UWS. Here, we addresses mind
      ascription to UWS patients in Germany. METHODS: We investigate the perception of
      UWS patients in a large German sample (N = 910) and compare the results to the
      previous US data, addressing possible cultural differences. We further assess
      effects of medical expertise, age, gender, socio-economic status and subjective
      knowledge about UWS in the German sample. RESULTS: Unlike the US sample, German
      participants did not perceive UWS patients as "more dead than dead", ascribing
      either equal (on 3 of 5 items) or more (on 2 items) mental abilities to UWS
      patients than to the dead. Likewise, an effect of implicit dualism was not
      replicated and German medically trained participants ascribed more capabilities
      to UWS patients than did a non-medical sample. Within the German sample, age,
      gender, religiosity and socio-economic status explained about 15% of the
      variability of mind ascription. Age and religiosity were individually significant
      predictors, younger and more religious people ascribing more mind. Gender had no
      effect. CONCLUSION: Results are consistent with cross-cultural differences in the
      perception of UWS between Germany and the USA, Germans ascribing more mind to UWS
      patients. The German sample ascribed as much or more but not less mind to a UWS
      patient than to a deceased, although within group variance was large, calling for
      further research. Mind ascription is vital, because, in times of declining
      resources for healthcare systems, and an increasing legalization of euthanasia,
      public opinion will influence UWS patients' rights and whether 'the right to die'
      will be the only right conceded to them.

PMID- 29467038
TI  - Clinical predictors of proteinuric remission following an LN flare - evidence
      from the UK JSLE cohort study.
AB  - BACKGROUND: Proteinuria is a well-known risk factor for progression of renal
      dysfunction in a variety of chronic kidney diseases. In adult-onset Systemic
      Lupus Erytematosus (SLE) patients with lupus nephritis (LN), proteinuria takes a
      significant period of time to normalise, with proteinuric remission being
      associated with improved renal survival and reductions in mortality. The length
      of time required to attain proteinuric remission has not previously been
      investigated in Juvenile-onset SLE (JSLE). The aim of this study was to elucidate
      when proteinuric remission occurs, and whether clinical/demographic factors at LN
      onset bear influence on the time to proteinuric remission. METHODS: Participants
      of the UK JSLE Cohort Study and Repository were included if they had active LN
      (renal biopsy and/or renal British Isles Lupus Assessment Grade (BILAG) score
      defined active LN) and proteinuria. Univariate Cox proportional hazard regression
      modelling was used to explore factors associated with time to proteinuric
      recovery. Covariates with p-value < 0.2 were included in a multivariable Cox
      regression model, and backward stepwise variable selection applied. RESULT:
      64/350 (18%) of UK JSLE Cohort Study patients fulfilled the study inclusion
      criteria. 25 (39%) achieved proteinuric remission within a median of 17 months
      (min 2.4, max 78). Within a multivariate Cox proportional hazard regression
      model, age at time of LN flare (p = 0.007, HR 1.384, CI 1.095-1.750), eGFR (p =
      0.035, HR 1.016, CI 1.001-1.030) and haematological involvement (p = 0.016, HR
      0.324, CI 0.129-0.812) at the time of LN onset were found to be significantly
      associated with time to proteinuric recovery. CONCLUSIONS: A significant
      proportion of children with LN have on-going proteinuria approximately two years
      after their initial flare. Poor prognostic factors all at time of LN onset
      include younger age, low eGFR, and concomitant haematological involvement.

PMID- 29467040
TI  - Knowledge sharing between general and pediatric emergency departments:
      connections, barriers, and opportunities.
AB  - CLINICIAN'S CAPSULE What is known about this topic? Evidence-based pediatric
      emergency care is variably applied across general and pediatric emergency
      departments. What did this study ask? What are the information-seeking patterns
      of pediatric emergency medicine network members? What did this study find? There
      remains a need to share successful methods of local dissemination and
      implementation across the network, and to leverage local professional champions
      such as clinical nurse liaisons. Why does this study matter to clinicians?
      Tailoring knowledge mobilization efforts to end-user priorities is essential to
      ensure impact and spread of outreach efforts.

PMID- 29467039
TI  - Influence of lifestyle characteristics and VDR polymorphisms as risk factors for
      intervertebral disc degeneration: a case-control study.
AB  - BACKGROUND: Intervertebral disc degeneration (DD) is an important cause of low
      back pain and its precise aetiology is not fully understood, being attributed to
      cumulative environmental, biomechanical and genetic effects. The vitamin D plays
      a key role in regulation of calcium homeostasis and bone mineralization, exerting
      its biological activities by binding to a high-affinity receptor (VDR).
      Polymorphisms in VDR gene were previously associated with DD process, however
      with conflicting results. Here, we aimed to investigate the influence of
      lifestyle characteristics and VDR TaqI, BsmI, ApaI and FokI polymorphisms as risk
      factors for DD process. METHODS: Retrospective case-control study involving 231
      participants: 119 with confirmed DD and 112 healthy controls. Genotyping of VDR
      polymorphisms was performed by PCR-RFLP and real-time PCR using TaqMan
      methodology. All patients answered a questionnaire regarding lifestyle
      characteristics, such as educational level, pain localization, smoking habits,
      engagement of physical activity, postural and load weight at work and familial
      history of disc degeneration. The variables were compared between groups and
      adjusted by age and gender. RESULTS: The case group was composed by 52% female
      and 48% male and the mean age was 40.0 years old, while in the control group 79%
      was female and 21% male and the mean age was 32.0 years old. Although gender
      distribution and mean age were different between groups, in the control group all
      participants were less than 45 years old and there was a prevalence of women in
      both groups. The factors that could be possibly associated to DD in the Brazilian
      population studied included smoking habits (26% in cases and 9% in controls, p =
      0.003), lack of engagement in physical activity (observed in 77% of cases and 62%
      of controls, p = 0.018), and loading weight during work routine (58% in cases and
      24% in controls, p <= 0.001). However, after adjusting by age and gender, only
      smoking habits remained associated to disc degeneration (p = 0.027). Considering
      the educational level, 35.2% of cases and 15.6% of controls had only the
      Elementary School, and 5.5% of DD group and 28.6% of control group had completed
      College (p = 0.025). In addition, educational level was directly associated to
      load weight at work (p = 0.012). Regarding VDR polymorphisms, no significant
      difference in genotype and allele frequencies between groups was observed. The
      haplotype analysis revealed that the combined wild-type alleles of TaqI, ApaI and
      FokI polymorphisms-TGT-was observed in a higher frequency in control group (p =
      0.039). CONCLUSION: The findings suggested that smoking habits was a risk factor
      for disc degeneration in the population studied. Single analysis revealed no
      significant effects of VDR polymorphisms in disc degeneration process, while the
      combination of wild-type alleles of TaqI, ApaI and FokI polymorphisms, TGT
      haplotype, decreased the risk of the disease.

PMID- 29467041
TI  - Interviewer effects in food acquisition surveys.
AB  - OBJECTIVE: To understand the effects of interviewers on the responses they
      collect for measures of food security, income and selected survey quality
      measures (i.e. discrepancy between reported Supplemental Nutrition Assistance
      Program (SNAP) status and administrative data, length of time between initial and
      final interview, and missing income data) in the US Department of Agriculture's
      National Household Food Acquisition and Purchase Survey (FoodAPS). DESIGN: Using
      data from FoodAPS, multilevel models with random interviewer effects were fitted
      to estimate the variance in each outcome measure arising from effects of the
      interviewers. Covariates describing each household's socio-economic status,
      demographics and experience in taking the survey, and interviewer-level
      experience were included as fixed effects. The variance components in the
      outcomes due to interviewers were estimated. Outlier interviewers were profiled.
      SETTING: Non-institutionalized households in the continental USA (April 2012
      January 2013). SUBJECTS: Individuals (n 14 317) in 4826 households who responded
      to FoodAPS. RESULTS: There was a substantial amount of variability in the
      distributions of the outcomes examined (i.e. time between initial and final
      interview, reported values for food security, individual income, missing income)
      among the FoodAPS interviewers, even after accounting for the fixed effects of
      the household- and interviewer-level covariates and removing extreme outlier
      interviewers. CONCLUSIONS: Interviewers may introduce error in food acquisition
      survey data when they are asked to interact with the respondents. Managers of
      future surveys with similarly complex data collection procedures could consider
      using multilevel models to adaptively identify and retrain interviewers who have
      extreme effects on data collection outcomes.

PMID- 29467042
TI  - Effect of selected plant species within biodiverse pasture on in vitro fatty acid
      biohydrogenation and tissue fatty acid composition of lamb.
AB  - The effect of botanical diversity on supply of polyunsaturated fatty acids (PUFA)
      to ruminants in vitro, and the fatty acid (FA) composition of muscle in lambs was
      investigated. Six plant species, commonly grown as part of UK herbal ley mixtures
      (Trifolium pratense, Lotus corniculatus, Achillea millefolium, Centaurea nigra,
      Plantago lanceolata and Prunella vulgaris), were assessed for FA profile, and in
      vitro biohydrogenation of constituent PUFA, to estimate intestinal supply of PUFA
      available for absorption by ruminants. Modelling the in vitro data suggested that
      L. corniculatus and P. vulgaris had the greatest potential to increase 18:3n-3
      supply to ruminants, having the highest amounts escaping in vitro
      biohydrogenation. Biodiverse pastures were established using the six selected
      species, under-sown in a perennial ryegrass-based sward. Lambs were grazed (~50
      days) on biodiverse or control pastures and the effects on the FA composition of
      musculus longissimus thoracis (lean and subcutaneous fat) and musculus
      semimembranosus (lean) were determined. Biodiverse pasture increased 18:2n-6 and
      18:3n-3 contents of m. semimembranosus (+14.8 and +7.2 mg/100 g tissue,
      respectively) and the subcutaneous fat of m. longissimus thoracis (+158 and +166
      mg/100 g tissue, respectively) relative to feeding a perennial ryegrass pasture.
      However, there was no effect on total concentrations of saturated FA in the
      tissues studied. It was concluded that enhancing biodiversity had a positive
      impact on muscle FA profile reflected by increased levels of total PUFA.

PMID- 29467043
TI  - Three-dimensional spheroid culture of adipose stromal vascular cells for studying
      adipogenesis in beef cattle.
AB  - Protocols designed for the adipogenic differentiation of human and mouse cells
      are commonly used for inducing the adipogenesis of bovine stromal vascular cells.
      However, likely due to metabolic differences between ruminant and non-ruminant
      animals, these methods result in only few cells undergoing complete adipogenesis
      with minimal lipid droplet accumulation. Here, we discuss the development of an
      adipogenic differentiation protocol for bovine primary cells through a three
      dimensional spheroid culture. Stromal vascular cells derived from bovine
      intramuscular fat were isolated and stored in liquid nitrogen before culturing.
      Cells were cultured in hanging drops for 3 days to allow for the formation of
      spherical structures. The spheroids were then transferred to cell culture plates
      with endothelial basal medium-2 for 3 days and in Dulbecco's Modified Eagle's
      Medium (DMEM) supplemented with a standard adipogenic cocktail for 3 additional
      days, which were then allowed to fully differentiate for 3 days in DMEM
      supplemented with insulin. Compared with conventional two-dimensional culture,
      cells in a three-dimensional spheroid culture system had higher adipogenic gene
      expression and consequently contained more adipocytes with larger lipid droplets.
      In addition, endothelial induction of spheroids prior to adipogenic
      differentiation is essential for efficient induction of adipogenesis of bovine
      stromal vascular cells, mimicking in vivo adipose development. In summary, the
      newly developed three-dimensional spheroid culture method is an efficient way to
      induce adipogenic differentiation and study adipose development of cells derived
      from ruminant animals, which also can be used for studying the role of
      angiogenesis in adipose development.

PMID- 29467044
TI  - Pedigree analysis and inbreeding effects over morphological traits in Campolina
      horse population.
AB  - Genetic improvement, without control of inbreeding, can go to loss of genetic
      variability, reducing the potential for genetic gains in the domestic
      populations. The aim of this study was to analyze the population structure and
      the inbreeding depression in Campolina horses. Phenotype information from 43 465
      individuals was analyzed, data provided by the Campolina Breeders Association. A
      pedigree file containing 107 951 horses was used to connected the phenotyped
      individuals. The inbreeding coefficient was performed by use of the diagonal of
      the relationship matrix and the genealogical parameters were computed using
      proper softwares. The effective population size was estimated based on the rate
      of inbreeding and census information, and the stratification of the population
      was verified by the average relationship coefficient between animals born in
      different regions of Brazil. The effects of inbreeding on morphological traits
      were made by the use of inbreeding coefficient as a covariate in the model of
      random regression. The inbreeding coefficient increased from 1990 on, impacting
      effective population size and, consequently, shrinking genetic variability. The
      paternal inbreeding was greater than maternal, which may be attributed to the
      preference for inbred animals in reproduction. The average genetic relationship
      coefficient of animals born in different states was lower than individuals born
      within the same state. The increase in the inbreeding coefficient was negatively
      associated with all studied traits, showing the importance to avoid genetic
      losses in the long term. Although results do not indicate a severe narrowing of
      the population until the present date, the average relationship coefficient shows
      signs of increase, which could cause a drastic reduction in genetic variability
      if inbred mating is not successfully controlled in the Campolina horse
      population.

PMID- 29467045
TI  - SYSTEMATIC REVIEW WITH NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS OF
      ROTATOR CUFF TEAR TREATMENT.
AB  - OBJECTIVES: Rotator cuff tear is the leading cause of the decline in quality of
      life for older adults, but comparative evidence on treatment effectiveness is
      lacking. This study systematically reviewed the effects of various rotator cuff
      tear treatments through a Bayesian meta-analysis of the related randomized
      clinical trials (RCTs). METHODS: We searched nine electronic databases for RCTs
      evaluating rotator cuff tear treatments from their inception through June 2017. A
      systematic review was performed following the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) and the National Institute for
      Health and Care Excellence-Decision Support Unit guidelines (Supplementary Table
      1). Outcomes included functional improvement, pain one year after surgical
      treatment, and tendon structural integrity. The Bayesian network meta-analysis
      was applied for functional improvement and pain, based on an assumption of
      consistency and similarity. Tendon integrity was reported descriptively. RESULTS:
      Fifteen RCTs were selected. Patients undergoing physiotherapy after open surgery
      showed statistically significant functional improvements compared with those
      undergoing physiotherapy only (mean differences, 9.1 [credible interval, 0.9
      17.4]). Open surgery with physiotherapy was associated with a decrease in pain 1
      year after treatment compared with when physiotherapy was combined with
      arthroscopic rotator cuff surgery, mini open surgery, platelet-rich plasma
      therapy, or physiotherapy alone (absolute value of mean difference 1.2 to 1.4).
      The tendon integrity results were inconsistent. CONCLUSIONS: Some surgical
      treatments were associated with significant improvement in function and pain, but
      evidence regarding their comparative effectiveness is still lacking. A well
      designed RCT discussing functional and structural treatment outcomes is needed in
      future.

PMID- 29467046
TI  - The interaction between monoamine oxidase A (MAOA) and childhood maltreatment as
      a predictor of personality pathology in females: Emotional reactivity as a
      potential mediating mechanism.
AB  - Research consistently demonstrates that common polymorphic variation in monoamine
      oxidase A (MAOA) moderates the influence of childhood maltreatment on later
      antisocial behavior, with growing evidence that the "risk" allele (high vs. low
      activity) differs for females. However, little is known about how this Gene *
      Environment interaction functions to increase risk, or if this risk pathway is
      specific to antisocial behavior. Using a prospectively assessed, longitudinal
      sample of females (n = 2,004), we examined whether changes in emotional
      reactivity (ER) during adolescence mediated associations between this Gene *
      Environment and antisocial personality disorder in early adulthood. In addition,
      we assessed whether this putative risk pathway also conferred risk for borderline
      personality disorder, a related disorder characterized by high ER. While direct
      associations between early maltreatment and later personality pathology did not
      vary by genotype, there was a significant difference in the indirect path via ER
      during adolescence. Consistent with hypotheses, females with high-activity MAOA
      genotype who experienced early maltreatment had greater increases in ER during
      adolescence, and higher levels of ER predicted both antisocial personality
      disorder and borderline personality disorder symptom severity. Taken together,
      findings suggest that the interaction between MAOA and early maltreatment places
      women at risk for a broader range of personality pathology via effects on ER.

PMID- 29467047
TI  - Myocardial stress perfusion magnetic resonance in children with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Microvascular dysfunction in hypertrophic cardiomyopathy has been
      associated with poor clinical outcome. Several studies have demonstrated a
      reduced perfusion reserve proportional to the magnitude of the hypertrophy. We
      investigated the utility of stress perfusion cardiac MRI to detect microvascular
      dysfunction in children with hypertrophic cardiomyopathy. METHODS: From January
      2016 to January 2017, 13 patients, with a mean age of 15.3 years, with
      hypertrophic cardiomyopathy underwent regadenoson stress perfusion cardiac MRI
      (1.5-T Siemens Aera). A single-shot, T1-weighted saturation recovery gradient
      echo was used for first-pass perfusion in a multiple-slices group, including
      three short-axis slices and one four-chamber slice. Coronary vasodilatory stress
      was achieved using bolus injection of regadenoson (lexiscan 0.4 mg/5 ml) and
      dynamic perfusion during rest and stress performed by administering 0.05 mmol/kg
      of gadolinium contrast agent (gadoteridol) injected at a rate of 3.5 ml/s,
      followed by assessment of viability using two-dimensional phase-sensitive
      inversion recovery of the entire myocardium. RESULTS: All patients completed
      protocols with no interruptions. In all, seven patients developed perfusion
      defects after the administration of regadenoson. Asymmetric septal hypertrophy
      was the most common pattern of hypertrophic cardiomyopathy (n=4) in those with
      abnormal perfusion. A total of four patients with perfusion defects had a maximum
      wall thickness <30 mm. The finding of perfusion defects in areas without late
      gadolinium enhancement in some of our patients indicates that gadolinium
      enhancement by itself could underestimate the true extension of microvascular
      disease. Out of seven patients, five patients with positive stress cardiac MRI
      have undergone implantable cardioverter defibrillator placement based on current
      guidelines. CONCLUSIONS: Regadenoson stress cardiac MRI is feasible and
      clinically valuable in paediatric patients. It is particularly effective in
      unmasking abnormal myocardial perfusion in the presence of microvascular
      dysfunction in children with hypertrophic cardiomyopathy.

PMID- 29467048
TI  - Pregnancy-associated spontaneous coronary artery dissection (PASCAD): An etiology
      for chest pain in the young peripartum patient.
AB  - Cardiac emergencies in pregnancy and the postpartum period are rare but often
      life-threatening. An emergency physician's differential diagnosis for chest pain
      in the peripartum patient often includes serious etiologies such as pulmonary
      embolism or myocardial infarction (MI). A lesser-known but important
      consideration on the differential for MI is that of a spontaneous coronary artery
      dissection (SCAD). SCAD is defined as an intramural hematoma within the coronary
      artery that compresses the true lumen. Expansion by increased pressures may lead
      to subsequent myocardial ischemia and infarction. This condition is the most
      common cause of pregnancy-associated MI and is reported as the cause of MI in 24%
      to 35% of all women younger than 50 years. This condition is predominately seen
      in young healthy females with no traditional risk factors for coronary artery or
      cardiac disease, and typically in the postpartum period. SCAD in the peripartum
      period is defined as pregnancy-associated spontaneous coronary artery dissection
      (PASCAD). Abnormal ECG changes, elevated troponins, and regional wall motional
      abnormalities on echocardiography are all diagnostic findings of SCAD, which can
      be ultimately confirmed with coronary angiography. Failure to immediately address
      this condition can lead to acute heart failure, cardiogenic shock, and death.
      Thrombolytic treatment may be harmful and is not recommended, and percutaneous
      coronary intervention can result in the iatrogenic propagation of further
      coronary dissection. As a result, the management for suspected SCAD involves
      emphasis on urgent transfer and urgent coronary artery angiography to determine
      appropriate treatment modalities.

PMID- 29467049
TI  - Developmental competence of cat (Felis domesticus) oocytes and embryos after
      parthenogenetic stimulation using different methods.
AB  - The aim of this study was to compare the effects of various activating factors on
      feline oocytes. The study included activation within the ovary (natural),
      activation during in vitro maturation (spontaneous activation), chemical
      activation (ionomycin + 6-DMAP), activation by spermatozoa and injection (ICSI)
      and mechanical activation (sham ICSI). According to our results, parthenogenetic
      embryos could emerge at every step of in vitro embryo production (IVP)
      procedures. After oocyte collection, 6% of parthenogenetic embryos were observed,
      mainly at the 2-4-blastomere stages. After 24 h of in vitro maturation,
      parthenogenetic activation was observed in 7% of oocytes. Using ionomycin and 6
      DMAP to artificially activate oocytes, 53% of cleaved embryos were obtained. The
      results after ICSI (54% cleaved embryos) were not significantly different from
      the results in Group III using chemical activation (53% cleaved embryos). But
      only after ICSI were blastocysts obtained (5/73.7%) as a result of in vitro
      culture. Moreover, embryos after ICSI were of the best morphological quality with
      minor levels of fragmentation evident in the embryos. After sham mechanical
      activation, 'sham ICSI', 8% of cleaved embryos were noted. Therefore, it is
      advised to maintain a negative control in parallel with each step of IVP
      techniques, to avoid misleading results. Chemical methods for artificial
      activation of feline oocytes are the most promising for application to the
      cloning and production of parthenogenetic embryos for experimental studies.

PMID- 29467050
TI  - Does the diurnal pattern of enteric methane emissions from dairy cows change over
      time?
AB  - Diet manipulation and genetic selection are two important mitigation strategies
      for reducing enteric methane (CH4) emissions from ruminant livestock. The aim of
      this study was to assess whether the diurnal pattern of CH4 emissions from
      individual dairy cows changes over time when cows are fed on diets varying in
      forage composition. Emissions of CH4 from 36 cows were measured during milking in
      an automatic (robotic) milking station in three consecutive feeding periods, for
      a total of 84 days. In Periods 1 and 2, the 36 cows were fed a high-forage
      partial mixed ration (PMR) containing 75% forage, with either a high grass silage
      or high maize silage content. In Period 3, cows were fed a commercial PMR
      containing 69% forage. Cows were offered PMR ad libitum plus concentrates during
      milking and CH4 emitted by individual cows was sampled during 8662 milkings. A
      linear mixed model was used to assess differences among cows, feeding periods and
      time of day. Considerable variation was observed among cows in daily mean and
      diurnal patterns of CH4 emissions. On average, cows produced less CH4 when fed on
      the commercial PMR in feeding Period 3 than when the same cows were fed on high
      forage diets in feeding Periods 1 and 2. The average diurnal pattern for CH4
      emissions did not significantly change between feeding periods and as lactation
      progressed. Emissions of CH4 were positively associated with dry matter (DM)
      intake and forage DM intake. It is concluded that if the management of feed
      allocation remains constant then the diurnal pattern of CH4 emissions from dairy
      cows will not necessarily alter over time. A change in diet composition may bring
      about an increase or decrease in absolute emissions over a 24-h period without
      significantly changing the diurnal pattern unless management of feed allocation
      changes. These findings are important for CH4 monitoring techniques that involve
      taking measurements over short periods within a day rather than complete 24-h
      observations.

PMID- 29467051
TI  - Primary Care Medical Practices: Are Community Health Care Providers Ready for
      Disasters?
AB  - OBJECTIVE: This study seeks to determine the capacity of community primary care
      practices to meet the needs of patients during public health emergencies and to
      identify the barriers and resources necessary to participate in a coordinated
      response with public safety agencies. METHODS: The self-administered web-based
      survey was distributed in January 2014 via e-mail to primary care providers in
      Pennsylvania using the listservs of several professional societies. RESULTS: A
      total of 179 primary care providers participated in the survey. In total, 38% had
      practice continuity of operations plan in place and 26% reported that they had a
      plan for patient surge in the outpatient setting. Thirty percent reported that
      they were registered on the state Health Alert Network and 41% said they were
      able to communicate with patients during disasters. Only 8% of providers reported
      that they believed that their patients with special health care needs were
      prepared for a disaster, although over two-thirds of responding practices felt
      they could assist these patients with disaster preparedness. Providers indicated
      that more information regarding government agency plans and community resources,
      patient education materials, and more time to devote to counseling during patient
      encounters would improve their ability to prepare their patients with special
      health care needs for disasters. Providers also reported that they would benefit
      from partnerships to help the practice during emergencies and communications
      technology to reach large numbers of patients quickly. CONCLUSIONS: Community
      based primary care practices can be useful partners during public health
      emergencies. Efforts to promote continuity of operations planning, improved
      coordination with government and community partners, as well as preparedness for
      patients with special health care needs, would augment their capabilities and
      contribute to community resilience. (Disaster Med Public Health Preparedness.
      2018;page 1 of 5).

PMID- 29467052
TI  - A systematic review and meta-analysis of the incidence of psychotic disorders:
      the distribution of rates and the influence of gender, urbanicity, immigration
      and socio-economic level.
AB  - BACKGROUND: Considering existing knowledge on the relationship between certain
      environmental factors and incidence rates of psychosis, we carried out a
      systematic review to provide a broad and updated picture of the incidences of
      different psychotic disorder subgroups worldwide and how some environmental
      factors influence these rates. METHODS: Studies with original data related to the
      incidence of psychosis (published between 2000 and 2015) were identified via
      searching electronic databases (CINAHL, MEDLINE, PSYCINFO, PUBMED, and SCOPUS).
      Data on the following risk factors were extracted: gender, urbanicity,
      immigration and socio-economic level. Descriptive appraisals of variation in
      incidence rates (IR) and incidence rate ratios (IRR), with a 95% confidence
      interval were calculated. In addition, a meta-analysis was performed to calculate
      IR pooled by diagnosis group and IRR pooled by diagnosis and gender, urbanity,
      immigration and socio-economic level, using a random effects model. RESULTS: We
      identified 33 reports to analyse. Overall IR per 100 000 persons for non
      affective psychoses (IR pooled = 22.53 (16.51-28.54)) were higher than affective
      psychoses (IR pooled = 7.12 (5.03-9.22)). There was an increase in rates of
      psychosis in men v. women (IRR pooled = 1.54 (1.37-1.72)), in urban v. rural
      areas (IRR pooled = 1.64 (1.38-1.95)), in immigrants v. natives (IRR pooled =
      3.09 (2.74-3.49)), and in lower socio-economic level areas (IRR pooled = 1.78
      (1.43-2.22)). CONCLUSIONS: IR among different psychotic disorders was found to
      vary depending on gender, urbanicity, and immigration (as most of the previous
      literature focuses on non-affective psychosis or schizophrenia).

PMID- 29467053
TI  - Randomized control trials demonstrate that nutrition-sensitive social protection
      interventions increase the use of multiple-micronutrient powders and iron
      supplements in rural pre-school Bangladeshi children.
AB  - OBJECTIVE: To examine the impact of a nutrition-sensitive social protection
      intervention on mothers' knowledge of Fe deficiency, awareness of multiple
      micronutrient powders (MMP) and the consumption of MMP and other Fe supplements
      by their children aged 6-59 months. DESIGN: Two randomized controlled trials with
      treatment arms including cash transfers, food transfers, cash and food transfers,
      cash and nutrition behaviour change communication (BCC), and food and nutrition
      BCC were implemented over two years. Both included a control group that received
      no transfer or BCC. Transfer recipients were mothers living in poor households
      with at least one child aged less than 2 years at baseline. Probit models were
      used to analyse endline data. SETTING: Rural areas in north-west and south
      Bangladesh. SUBJECTS: Mothers (n 4840) and children 6-59 months (n 4840).
      RESULTS: A transfer accompanied by nutrition BCC increased the share of mothers
      with knowledge of Fe deficiency (11.9 and 9.2 percentage points for North and
      South, respectively, P<=0.01), maternal awareness of MMP (29.0 and 22.2
      percentage points, P<=0.01), the likelihood that their children 6-59 months had
      ever consumed MMP (32 and 11.9 percentage points, P<=0.01), consumed MMP in the
      preceding week (16.9 and 3.9 percentage points, P<=0.01) and consumed either MMP
      or an Fe supplement in the preceding week (22.3 and 7.1 percentage points,
      P<=0.01). Improvements were statistically significant relative to groups that
      received a transfer only. CONCLUSIONS: Nutrition-sensitive social protection
      (transfers with BCC added) may be a promising way to advance progress on
      micronutrient deficiencies.

PMID- 29467054
TI  - A new surgical procedure for type II total anomalous pulmonary venous drainage.
AB  - We report two cases of successful surgical repair of total anomalous pulmonary
      venous drainage. Our new surgical procedure for type IIa and IIb total anomalous
      pulmonary venous drainage has more advantages than the conventional rerouting
      method using an artificial or native pericardial patch.

PMID- 29467055
TI  - Molecular serogrouping of Escherichia coli.
AB  - O-antigens present on the surface of Escherichia coli provide antigenic
      specificity for the strain and are the main components for O-serogroup
      designation. Serotyping using O-group-specific antisera for the identification of
      E. coli O-serogroups has been traditionally the gold-standard for distinguishing
      E. coli strains. Knowledge of the O-group is important for determining pathogenic
      lineage, classifying E. coli for epidemiological studies, for determining
      virulence, and for tracing outbreaks of diseases and sources of infection.
      However, serotyping has limitations, as the antisera generated against each
      specific O-group may cross-react, many strains are non-typeable, and others can
      autoagglutinate or be rough (lacking an O-antigen). Currently, the nucleotide
      sequences are available for most of the 187 designated E. coli O-groups. Public
      health and other laboratories are considering whole genome sequencing to develop
      genotypic methods to determine O-groups. These procedures require instrumentation
      and analysis that may not be accessible and may be cost-prohibitive at this time.
      In this review, we have identified unique gene sequences within the O-antigen
      gene clusters and have targeted these genes for identification of O-groups using
      the polymerase chain reaction. This information can be used to distinguish O
      groups by developing other platforms for E. coli diagnostics in the future.

PMID- 29467056
TI  - Review: Integrating a semen quality control program and sire fertility at a large
      artificial insemination organization.
AB  - The technology available to assess sperm population characteristics has advanced
      greatly in recent years. Large artificial insemination (AI) organizations that
      sell bovine semen utilize many of these technologies not only for novel research
      purposes, but also to make decisions regarding whether to sell or discard the
      product. Within an AI organization, the acquisition, interpretation and
      utilization of semen quality data is often performed by a quality control
      department. In general, quality control decisions regarding semen sales are often
      founded on the linkages established between semen quality and field fertility.
      Although no one individual sperm bioassay has been successful in predicting sire
      fertility, many correlations to various in vivo fertility measures have been
      reported. The most powerful techniques currently available to evaluate semen are
      high-throughput and include computer-assisted sperm analysis and various flow
      cytometric analyses that quantify attributes of fluorescently stained cells.
      However, all techniques measuring biological parameters are subject to the
      principles of precision, accuracy and repeatability. Understanding the
      limitations of repeatability in laboratory analyses is important in a quality
      control and quality assurance program. Hence, AI organizations that acquire
      sizeable data sets pertaining to sperm quality and sire fertility are well
      positioned to examine and comment on data collection and interpretation. This is
      especially true for sire fertility, where the population of AI sires has been
      highly selected for fertility. In the December 2017 sire conception rate report
      by the Council on Dairy Cattle Breeding, 93% of all Holstein sires (n=2062)
      possessed fertility deviations within 3% of the breed average. Regardless of the
      reporting system, estimates of sire fertility should be based on an appropriate
      number of services per sire. Many users impose unrealistic expectations of the
      predictive value of these assessments due to a lack of understanding for the
      inherent lack of precision in binomial data gathered from field sources. Basic
      statistical principles warn us of the importance of experimental design, balanced
      treatments, sampling bias, appropriate models and appropriate interpretation of
      results with consideration for sample size and statistical power. Overall, this
      review seeks to describe and connect the use of sperm in vitro bioassays, the
      reporting of AI sire fertility, and the management decisions surrounding the
      implementation of a semen quality control program.

PMID- 29467057
TI  - Prevalence and predictors of involuntary psychiatric hospital admissions in
      Ontario, Canada: a population-based linked administrative database study.
AB  - BACKGROUND: Involuntary admissions to psychiatric hospitals are common; however,
      research examining the trends in prevalence over time and predictors is limited.
      Aims To examine trends in prevalence and risk factors for involuntary admissions
      in Ontario, Canada. METHOD: We conducted an analysis of all mental health bed
      admissions from 2009 to 2013 and assessed the association between patient
      sociodemographics, service utilisation, pathway to care and severity
      characteristics for involuntary admissions using a modified Poisson regression.
      RESULTS: We found a high and increasing prevalence of involuntary admissions
      (70.7% in 2009, 77.1% in 2013, 74.1% overall). Individuals with police contact in
      the prior week (risk ratio (RR) = 1.20) and immigrants both experienced greater
      likelihood of being involuntarily admitted, regardless of control for other
      characteristics (RR = 1.07) (both P < 0.0001). CONCLUSIONS: We identified
      numerous modifiable and non-modifiable risk factors for involuntary admissions.
      The prevalence of involuntary admissions was high, linearly increasing over time.
      Declaration of interest The authors have completed the ICMJE Form for Disclosure
      of Potential Conflicts of Interest and none were reported. This study was
      conducted using funding entirely from public sources. P.K. has received
      operational support via an Ontario Ministry of Health and Long-Term Care (MOHLTC)
      Health Services Research Fund Capacity Award to support this project. The
      Institute for Clinical Evaluative Sciences (ICES) is funded by the Ontario
      MOHLTC. The study results and conclusions are those of the authors, and should
      not be attributed to any of the funding agencies or sponsoring agencies. No
      endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. All
      decisions regarding study design, publication, and data analysis were made
      independent of the funding agencies.

PMID- 29467058
TI  - Trends in female authorship in research papers on eating disorders: 20-year
      bibliometric study.
AB  - BACKGROUND: There is a clear gender gap in scientific authorship. Although the
      proportions of female authors in medicine and psychiatry have increased over the
      past decades, women are still underrepresented. Aims To analyse authorship gender
      trends in eating disorder research. METHOD: First and last author gender in
      research articles on eating disorders during the period 1997-2016 were assessed
      in eating disorder specialty journals, high-impact psychiatry journals and high
      impact clinical psychology journals. RESULTS: The total number of papers on
      eating disorders increased substantially over the observation period, although a
      decrease was observed in high-impact psychiatry journals. Female authorship
      increased in both specialty journals and high-impact psychiatry journals. Authors
      were significantly less likely to be female in high-impact psychiatry and
      clinical psychology journals than in speciality journals. CONCLUSIONS: Eating
      disorder research has been increasingly allocated to specialty journals over the
      past 20 years. A consistent gender gap between specialty and high-impact journals
      exists. Declaration of interest C.M.B is a grant recipient from Shire
      Pharmaceuticals, Inc. and has participated as a member of their scientific
      advisory board. These positions are unrelated to the content of this article.

PMID- 29467059
TI  - Creation of a Collaborative Disaster Preparedness Video for Daycare Providers:
      Use of the Delphi Model for the Creation of a Comprehensive Disaster Preparedness
      Video for Daycare Providers.
AB  - OBJECTIVE: Eight million American children under the age of 5 attend daycare and
      more than another 50 million American children are in school or daycare settings.
      Emergency planning requirements for daycare licensing vary by state. Expert
      opinions were used to create a disaster preparedness video designed for daycare
      providers to cover a broad spectrum of scenarios. METHODS: Various stakeholders
      (17) devised the outline for an educational pre-disaster video for child daycare
      providers using the Delphi technique. Fleiss kappa values were obtained for
      consensus data. A 20-minute video was created, addressing the physical,
      psychological, and legal needs of children during and after a disaster. Viewers
      completed an anonymous survey to evaluate topic comprehension. RESULTS: A
      consensus was attempted on all topics, ranging from elements for inclusion to
      presentation format. The Fleiss kappa value of 0.07 was obtained. Fifty-seven of
      the total 168 video viewers completed the 10-question survey, with comprehension
      scores ranging from 72% to 100%. CONCLUSION: Evaluation of caregivers that viewed
      our video supports understanding of video contents. Ultimately, the technique
      used to create and disseminate the resources may serve as a template for others
      providing pre-disaster planning education. (Disaster Med Public Health
      Preparedness. 2018;page 1 of 5).

PMID- 29467060
TI  - Roman concrete for durable, eco-friendly construction - applications for tidal
      power generation, and protection against sea level rise.

PMID- 29467061
TI  - Doing away with variables.

PMID- 29467062
TI  - Global restriction of using antibiotic growth promoters and alternative
      strategies in poultry production.
AB  - A growing global concern of antibiotic use in poultry diets due to its potential
      adverse effects on birds and human health, food safety and the environment has
      led to a complete ban or restricted use in some countries, and, at the same time,
      expanding options for the use of alternative feed additives. Multiple, rather
      than a single additive may replace antibiotic growth promoters (AGPs) in poultry.
      Blending of feeding additives and hygienic farm management, vaccination and
      biosecurity may help achieve good intestinal health, stabilise enteric ecosystems
      and result in sustainable and cost effective production performance of birds.
      Moreover, controlling unsolicited ingredients at the production level must have
      the support of different markets responsible for the supply of safe and quality
      poultry products for consumers. This requires the further increase and
      diversification of value added poultry products and the expansion of their
      markets through strategic planning and gradual limitation of live bird markets.
      More research is warranted in order to explore suitable, reliable and cost
      effective alternatives to AGPs for commercial use, and strategic poultry value
      chain development.

PMID- 29467063
TI  - Time to Reset and Recharge.

PMID- 29467064
TI  - Don Bastain: Becoming a Consultant Pharmacist.

PMID- 29467065
TI  - Medication Refusal: Resident Rights, Administration Dilemma.
AB  - Occasionally, residents actively or passively refuse to take medications.
      Residents may refuse medication for a number of reasons, including religious
      beliefs, dietary restrictions, misunderstandings, cognitive impairment, desire to
      self-harm, or simple inconvenience. This action creates a unique situation for
      pharmacists and long-term facility staff, especially if patients have dementia.
      Residents have the legal right to refuse medications, and long-term care
      facilities need to employ a process to resolve disagreement between the health
      care team that recommends the medication and the resident who refuses it. In some
      cases, simple interventions like selecting a different medication or scheduling
      medications in a different time can address and resolve the resident's objection.
      If the medical team and the resident cannot resolve their disagreement, often an
      ethics consultation is helpful. Documenting the resident's refusal to take any or
      all medications, the health care team's actions and any other outcomes are
      important. Residents' beliefs may change over time, and the health care team
      needs to be prepared to revisit the issue as necessary.

PMID- 29467066
TI  - Balanitis: A Unique Presentation of Diabetes in an Elderly Male.
AB  - While diabetes is a common medical condition, the initial presentation of
      patients with diabetes may vary. In some cases, different types of infections or
      inflammatory conditions may prompt a patient to seek medical attention. Males may
      present to their primary care provider with a bothersome inflammation of the
      penis that may be the first recognition of previously undiagnosed diabetes.
      Balanitis is an inflammation of the glans of the penis that may prompt a patient
      to seek medical care. While there are several different causes of balanitis,
      underlying medical conditions such as uncontrolled diabetes have been associated
      with balanitis. The genital irritation prompts patients to seek medical
      evaluation, and at that point diabetes is diagnosed. It is important for
      pharmacists to recognize that balanitis is a potential though uncommon type of
      diabetes presentation. It is also important for pharmacists to review other
      aspects of diabetes care once a patient is diagnosed with diabetes.

PMID- 29467067
TI  - A Brief Review of Caprylidene (Axona) and Coconut Oil as Alternative Fuels in the
      Fight Against Alzheimer's Disease.
AB  - Type 3 diabetes mellitus has been coined to describe an alternative pathologic
      pathway of Alzheimer's disease (AD). The insulin resistance and impaired insulin
      signaling seen on positron-emission tomography scans in the brain of those
      affected by AD support this disease hypothesis. Two products-the medical food
      caprylidene (Axona) and coconut oil-seek to target the underlying pathology of
      type 3 diabetes mellitus by providing an alternative fuel source in the brain.
      Rather than improving glucose utilization, these two products seek to supply
      ketone bodies in sufficient quantities to pass through the blood-brain barrier
      and provide an alternative energy source to glucose. This review will provide an
      overview of the research behind these two modalities, as well as information
      necessary to ensure the safe use of these supplements.

PMID- 29467068
TI  - Comparison of Two Versions of the Beers Criteria and Adverse Outcomes in Older
      Hospitalized Patients.
AB  - OBJECTIVE: To compare the performance of the 2003 and 2012 Beers criteria (BC) to
      predict negative clinical outcomes associated with potentially inappropriate
      medications in hospitalized older adults. DESIGN: Retrospective cohort study.
      SETTING: Acute Care of Elders (ACE) unit in a community-based teaching hospital.
      PARTICIPANTS: All patients admitted to an ACE unit who were older than 65 years
      of age and prescribed at least one medication upon hospital admission. MAIN
      OUTCOME MEASURE(S): The primary outcome was hospital length of stay (LOS).
      Secondary outcomes included likelihood of experiencing adverse drug events (ADEs)
      and in-hospital mortality. RESULTS: A total of 340 patients were included in this
      study. Inpatients prescribed a BC drug at any time had a longer hospital LOS than
      those not prescribed a BC drug (2003 BC: adjusted geometric mean, 5.93 vs. 5.50
      days, P = 0.003; 2012 BC: adjusted geometric mean, 5.87 vs. 4.21 days, P <
      0.001). Patients prescribed a 2003 BC drug had an increased risk of experiencing
      an ADE compared with those not prescribed a BC drug (odds ratio [OR] = 1.86, 95%
      confidence interval [CI] 1.11-3.11); however, this outcome was not statistically
      significant after adjusting for confounders (OR = 1.51, 95% CI 0.870-2.63). There
      was no statistically significant difference in ADEs when using the 2012 BC
      (adjusted OR = 1.27, 95% CI 0.689-2.33). There was no difference in hospital
      mortality regardless of the BC version used. CONCLUSION: Prescription of BC drugs
      in an acute care setting is associated with an increased hospital LOS; however,
      there is no difference in the risk of ADEs or in-hospital mortality.

PMID- 29467069
TI  - Determination of Anticholinergic Medication Use in Patients Prescribed
      Medications for the Treatment of Dementia.
AB  - OBJECTIVE: The primary endpoint of the study is to determine the variations in
      the use of medications to treat dementia in patients concomitantly or not
      prescribed anticholinergics. DESIGN: The study is a case series of patients at a
      single community pharmacy over one year based on prescription claims data.
      SETTING: The setting is an independent community pharmacy in the South. MAIN
      OUTCOME MEASURE(S): The main outcome is the variations associated in treatment
      plans for patients either receiving anticholinergics or not receiving medications
      with anticholinergic properties. RESULTS: The community pharmacy had 33 patients
      on medications to treat dementia, and 17 patients (51.5%) were prescribed
      anticholinergic medications. Only patients on anticholinergic medications were
      prescribed memantine immediate-release. Fifteen patients (93%) not prescribed
      anticholinergic medications were on a single medication to treat dementia,
      whereas 9 patients (52%) prescribed anticholinergic medications were on a single
      medication to treat dementia. CONCLUSION: Further research should be conducted in
      this area to better ascertain the impact anticholinergic medications have on
      patients. This study noted differences from previous data regarding the
      prevalence of concomitant prescribing of medications for the treatment of
      dementia and anticholinergics.

PMID- 29467070
TI  - Congress Quiet on Long-Term Care, but Agencies Continue to Work.

PMID- 29467071
TI  - Relative contribution of overweight and obesity to rising public hospital in
      patient expenditure in South Australia.
AB  - Objective Arguments to fund obesity prevention have often focused on the growing
      hospital costs of associated diseases. However, the relative contribution of
      overweight and obesity to public hospital expenditure growth is not well
      understood. This paper examines the effect of overweight and obesity on acute
      public hospital in-patient expenditure in South Australia over time compared with
      other expenditure drivers.Methods Annual inflation-adjusted acute public admitted
      expenditure attributable to a high body mass index was estimated for 2007-08 and
      2011-12 and compared with other expenditure drivers.Results Expenditure
      attributable to overweight and obesity increased by A$45million, from 4.7% to
      5.4% of total acute public in-patient expenditure. This increase accounted for
      7.8% of the A$583million total expenditure growth, whereas the largest component
      of total growth (62.4%) was a real increase in the average cost per
      separation.Conclusions The relatively minor contribution of overweight and
      obesity to expenditure growth over the time period examined invites reflection on
      arguments to boost preventive spending that centre upon reducing hospital costs.
      These arguments may inadvertently detract attention from the considerable health
      and social burdens of overweight and obesity and from unrelated sources of
      expenditure growth that reduce opportunities for state governments to fund
      obesity prevention programs despite their comparative benefits to population
      health.What is known about the topic? Stand-alone estimates suggest that
      overweight and obesity are placing a considerable financial burden on the
      Australian public healthcare system.What does this paper add? Our findings
      challenge common perceptions about the relative importance of overweight and
      obesity in the context of rising public in-patient expenditure in Australia.What
      are the implications for practitioners? Consistent serial estimates of overweight
      and obesity-attributable expenditure enable its tracking and comparison with
      other potentially controllable expenditure drivers that may also warrant
      attention. Explicit consideration of population health trade-offs in expenditure
      related decisions, including in enterprise bargaining, would enhance transparency
      in priority setting.

PMID- 29467072
TI  - Social Gradients in Myocardial Infarction and Stroke Diagnoses in Emergency
      Medicine.
AB  - BACKGROUND: Persons of lower socio-economic status are at higher risk of disease,
      especially with respect to severe and chronic illnesses. To date, there have not
      been any studies with large case numbers regarding acute medical emergencies in
      this population. METHODS: In a retrospective study, data were obtained on all
      cases treated by emergency physicians in Bochum, Germany, in 2014/2015, including
      the diagnoses that were made by the emergency physicians. There were a total of
      16 767 cases. The local unemployment rate was taken as an indicator of the
      socioeconomic situation of a neighborhood; it was defined as the percentage of
      registered unemployed persons among persons aged 15 to 64 with their domicile in
      the neighborhood. 12 168 cases were grouped by emergency medical diagnosis and
      analyzed with respect to the three most heavily represented diagnostic categories
      (cardiovascular, neurological, and pulmonary emergencies), which accounted for
      nearly two-thirds of all diagnoses. RESULTS: The overall rates of deployment
      involving emergency physicians were found to be positively correlated with the
      unemployment rate. After adjustment for age, sex, and possible confounders, this
      correlation was statistically significant (p<0.01). The indirectly standardized
      rate ratio (IRR) for the overall case-activity rate ranged from 0.841 (95%
      confidence interval: [0.808; 0.875]) with less than 5% unemployment to 1.212
      [1.168; 1.256] with 9.5% unemployment or higher. The same finding was obtained
      with respect to diagnosis-specific case activity in each of the three main
      diagnostic categories (cardiovascular, neurological, and pulmonary emergencies),
      as well as for the respective commonest individual diagnoses (acute coronary
      syndrome/circulatory arrest [1498 cases], transient ischemic attack/ischemic
      stroke/intracerebral hemorrhage [1274 cases], and asthma/chronic obstructive
      pulmonary disease [663 cases]). CONCLUSION: This study shows that the case
      activity rate of the emergency medical services is significantly higher in
      socially disadvantaged neighborhoods, both with respect to total numbers and with
      respect to individual diseases. It demonstrates a problem affecting society as a
      whole, which should be taken into account in the organization of medical rescue
      services.

PMID- 29467073
TI  - The Consumption of New Psychoactive Substances and Methamphetamine.
AB  - BACKGROUND: The abuse of new psychoactive substances (NPS) and methamphetamine
      has severe adverse effects. Here we provide the first report of regional patterns
      in NPS and methamphetamine consumption in Germany, on the basis of epidemiologic
      data from six federal states (Bavaria, Hamburg, Hesse, North Rhine-Westphalia,
      Saxony, and Thuringia). METHODS: Data were derived from the 2015 Epidemiological
      Survey of Substance Abuse (Epidemiologischer Suchtsurvey) and supplemented with
      additional cases from the federal states that were studied. The numbers of
      persons included in the representative samples of persons aged 18 to 64 in each
      state were 1916 (Bavaria), 1125 (Hamburg), 1151 (Hesse), 2008 (North Rhine
      Westphalia), 1897 (Saxony), and 1543 (Thuringia). Potential risk factors for the
      lifetime prevalence of consumption were studied by logistic regression. RESULTS:
      The lifetime prevalence of methamphetamine consumption in the individual states
      ranged from 0.3% (North Rhine-Westphalia) to 2.0% (Saxony). Thuringia and Saxony
      displayed values that were significantly higher than average. For NPS, the
      figures ranged from 2.2% (Bavaria) to 3.9% (Hamburg), but multivariate analysis
      revealed no statistically significant differences between the states. Higher age
      and higher educational level were associated with lower consumption of NPS and
      methamphetamine, while smoking and cannabis use were each associated with higher
      consumption. CONCLUSION: NPS consumption is equally widespread in all of the
      federal states studied. Methamphetamine is rarely consumed; its consumption
      appears to be higher in Saxony and Thuringia. The risk factor analysis reported
      here should be interpreted cautiously in view of the low case numbers with
      respect to consumption.

PMID- 29467074
TI  - The Interventional Effect Cannot Be Interpreted.

PMID- 29467075
TI  - PFO Closure and Stroke.

PMID- 29467076
TI  - In Reply.

PMID- 29467077
TI  - Septic Nonunion in the Left Femoral Shaft of a 22-Year-Old Asylum-Seeker.

PMID- 29467078
TI  - Acute Pulmonary Hemorrhage in a Patient With Disseminated Pulmonary Nodules.

PMID- 29467079
TI  - Narrowband UV-B Phototherapy in the Treatment of Generalized Hailey-Hailey
      Disease.

PMID- 29467080
TI  - Intraductal papillary neoplasm of the bile duct: A diagnostic challenge for
      optimal treatment.

PMID- 29467081
TI  - Fecal incontinence in older patients. A narrative review.
AB  - Fecal incontinence is one of the leading causes for the institutionalization of
      people in the last decades of life, associated with a great psychosocial and
      economic burden. The literature is scarce in this population group, due to the
      absence of universally accepted criteria to define "elderly patients" and
      difficulties in detection and diagnostic. The aim of this article was to conduct
      a narrative review of the main aspects related to fecal incontinence in older
      patients, providing management support. Toileting assistance, dietary change,
      controlling stool consistency and medical treatment can be used to treat these
      patients. Nevertheless, other therapies, such as biofeedback, neuromodulation or
      surgical treatment, can be considered in selected patients.

PMID- 29467082
TI  - National survey on airway and difficult airway management in intensive care
      units.
AB  - OBJECTIVE: To know organization, management and training in airway (AW) in
      Spanish Intensive Care Units (ICUs), with special interest in difficult airway
      (DAW). DESIGN: Descriptive cross-sectional study and chi2 subanalysis, conducted
      through a national survey from november 1th to december 15th, 2016. With the
      SEMICYUC's support, an online questionnaire of 27 items was sent to 179 ICUs.
      SETTING: ICUs of public, private centers, and consortia. RESULTS: In total, 101
      units responded (56.4%), corresponding to 1,827 beds and almost 95,000
      incomes/year. The 85.1% are public hospitals, and 83.2% had residents. Of the
      responders, 22.8% don't use routinely AW assessment scales, being the most
      frequently used the Cormack-Mallampati association (35.6%). There's not
      intubation (IOT) protocol in 77.2%, nor DAW protocol in 75.2%. An 82.2% have a
      DAW cart. The 48.5% have training in IOT, and in VAD 53.5%. Having a DAW expert
      is significantly associated with greater training in IOT (60% vs. 39.3%; P=.03),
      DAW (64.4% vs. 44.6%; P=.04), and more AW protocols (73.4% vs. 37.5%; P=.000).
      Having an specific guideline for DAW management in UCI is considered necessary in
      99%. CONCLUSIONS: There is room for improvement in AW management. It's necessary
      to identify an expert in DAW in each Unit, and the development of an specific
      guideline for DAW management in critical care.

PMID- 29467083
TI  - Bilateral hydrosalpinx in patients with Hirschsprung's disease.
AB  - PURPOSE: Hirschsprung's disease (HD) is uncommon in females. There are very few
      reports on the patients' obstetric and gynecological outcome. Hydrosalpinx causes
      pain and infertility. It is rare in nonsexually active teenagers. It may be
      because of an intrinsic disease of the fallopian tubes or secondary to surgery.
      AIM: to describe the relationship between hydrosalpinx and HD or its surgical
      approach; to report the impact of bilateral hydrosalpinx on fertility in HD.
      METHODS: The records of all females with HD since 1980 were reviewed. Only
      patients who reached menarche were included. Prevalence of hydrosalpinx and
      hydrosalpinx-free survival were compared after abdominoperineal (A) or transanal
      (T) surgery. Treatment for hydrosalpinx was reviewed. RESULTS: Seventeen out of
      27 patients had reached menarche (Group A: 13 patients; Group T: 4 patients).
      Five patients in group A and none in group T presented bilateral hydrosalpinx
      (p=0.261). There were no statistical differences in hydrosalpinx-free survival
      between groups (p=0.344). Hydrosalpinx treatment: two bilateral and one
      unilateral salpingectomy, one pyosalpinx evacuation and one untreated. Three
      patients had conception desire: one has children; two are on IVF program.
      CONCLUSION: An association between hydrosalpinx and HD was observed. The
      development of hydrosalpinx was not associated with surgical approach in our
      study. Females with HD should have a gynecological follow-up for the development
      of hydrosalpinx, which can impair fertility. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 29467084
TI  - [Social determinants of health at distinct levels by gender: education and
      household in Spain].
AB  - OBJECTIVE: To explore from a gender perspective the association with subjective
      health of the interaction between education and household arrangements within the
      framework of social determinants of health placed at the micro and mezzo levels.
      METHODS: The data comes from the Spanish sample of the European Union Statistics
      on Income and Living Conditions for 2014. Independent logistic regression models
      for men and women were run to analyze the association with subjective health of
      the interaction between education and household arrangements. An additive model
      was run to assess possible advantages over the interaction approach. RESULTS: The
      interaction models show a lower or even no significant effect on health of
      household arrangements usually negatively associated with health among
      individuals with high education, displaying specific patterns according to sex.
      CONCLUSIONS: Health profiles of women and men are more precisely drawn if both
      social determinants of health are combined. Among the women, the important role
      was confirmed of both social determinants of health in understanding their health
      inequalities. Among the men, mainly those with low educational achievement, the
      interaction revealed that the household was a more meaningful social determinant
      of health. This could enable the definition of more efficient public policies to
      reduce health and gender inequalities.

PMID- 29467085
TI  - Persistence of bacterial DNA in orthopedic infections.
AB  - Polymerase chain reaction (PCR) has been proposed as a method to identify
      bacteria in clinical samples because it is more sensitive than culture techniques
      and can produce results rapidly. However, PCR can detect DNA from dead cells and
      thus cannot distinguish between live and dead cells in a tissue sample. Killed
      Staphylococcus aureus cells were implanted into the femurs and knee joints of
      rats to determine the length of time that DNA from dead cells is detectable in a
      living animal under conditions similar to common orthopedic infections. In the
      joint infection model studied here, the DNA from the dead planktonic bacteria was
      detected using PCR immediately after injection or 24 h later, but was
      undetectable 48 and 72 h after injection. In the biofilm implanted-device model
      studied, the DNA from these dead biofilm cells was detected by PCR immediately
      after implantation and at 24 h, but not at 48 or 72 h. Thus, our results indicate
      that DNA from dead cells does not persist in these animal model systems for more
      than 2 days, which should reduce concerns about possible false positive results
      using molecular DNA-based techniques for the detection of pathogens.

PMID- 29467086
TI  - The application of moving bed bio-reactor (MBBR) in commercial laundry wastewater
      treatment.
AB  - Large, laboratory scale biological treatment tests of real industrial wastewater,
      generated in a large industrial laundry facility, was conducted from October 2014
      to January 2015. This research sought to develop laundry wastewater treatment
      technology which included tests of a two-stage Moving Bed Bio Reactor (MBBR);
      this had two reactors, was filled with carriers Kaldnes K5 (specific area - 800
      m2/m3) and were realized in aerobic condition. Operating on site, in the laundry,
      reactors were fed actual wastewater from the laundry retention tank. The laundry
      wastewater contained mainly surfactants and impurities originating from washed
      fabrics; a solution of urea to supplement nitrogen content and a solution of acid
      to correct pH were added. The daily flow of raw wastewater Qd varied from 0.6-1.0
      m3/d. Wastewater quality indicators showed that the reduction of pollutants was
      obtained: BOD5 by 95-98%, COD by 89-94%, the sum of anionic and nonionic
      surfactants by 85-96%. The quality of the purified wastewater after the start-up
      period met legal requirements regarding the standards for wastewater discharged
      into the environment.

PMID- 29467087
TI  - Simulated internal jugular vein cannulation using a needle-guiding device.
AB  - BACKGROUND: Using a two-dimensional ultrasound-guided approach does not guarantee
      success during the first attempt at internal jugular vein cannulation. Our
      randomized, parallel simulation study examined whether a new disposable device
      could improve the success rate of the first attempt at ultrasound-guided internal
      jugular vein cannulation of a simulated internal jugular vein. METHODS: Eighty
      eight participants were randomized to perform needle insertion for internal
      jugular vein cannulation of a phantom using the ultrasound-guided approach with
      (case group) or without (control group) this new device. The primary outcome was
      the success rate of the first attempt. The secondary outcome was the frequency of
      mechanical complications such as arterial puncture and posterior wall puncture,
      procedure time, and level of difficulty. RESULTS: Among 44 participants using the
      device, 33 (75.0%) achieved successful cannulation on the first attempt. However,
      only 12 (27.3%) of the 44 participants not using the device recorded success
      during the first attempt (risk difference, 0.477; 95% confidence interval [CI]
      0.294-0.661; P<0.001). The number of attempts was significantly lower (risk
      difference, -3.955; 95% CI, -5.014 to -3.712; P<0.001) when participants
      performed cannulation with the device (1.63+/-1.71) than without the device
      (5.59+/-5.78). Our study also showed that participants were comfortable when
      performing the ultrasound-guided approach with the new device (risk difference, 
      1.955; 95% CI, -2.016 to -1.493; P<0.0001). CONCLUSIONS: The new disposable
      device was effective for successful first attempts at needle insertion during
      ultrasound-guided internal jugular vein cannulation. Future clinical trials are
      needed to assess the effectiveness of this device.

PMID- 29467088
TI  - Do Reduced Copayments Affect Mortality after Surgery due to Stroke? An
      Interrupted Time Series Analysis of a National Cohort Sampled in 2003-2012.
AB  - BACKGROUND: The South Korean government introduced a policy in 2 phases, in
      September 2005 and in January 2010, for reducing copayments for patients with
      critical diseases, including stroke, to prevent excessive medical expenditures
      and to ease economic barriers. Previous studies of the effect of this policy were
      focused primarily on cancer. Therefore, we investigated the relationship between
      this policy and 1-year mortality after surgery among patients with stroke.
      METHODS: We used data from the Korean National Health Insurance sampling cohort
      (n = 2173 in 2003-2012) and performed an interrupted time series analysis.
      RESULTS: Approximately 26% of the patients died within 1 year after surgery. The
      time trends after reducing copayments from 10% to 5% (phase 2) were inversely
      associated with risk of 1-year mortality (relative risk = .855, 95% confidence
      interval: .749-.975; P = .0196). In addition, this inverse association was
      greater in patients with low incomes, of older ages, and with higher Charlson
      comorbidity indices. CONCLUSIONS: The introduction of a policy for reducing
      copayments to ease excessive cost burdens for patients with stroke was positively
      associated with a reduced risk of 1-year mortality after surgical treatment due
      to stroke. On the basis of our results, health policy makers should make an
      effort to identify vulnerable populations and to overcome economic barriers for
      providing effective alternatives to ensure patients receive optimal health care.

PMID- 29467089
TI  - ?

PMID- 29467090
TI  - Chin Position: to treat or not to treat.
AB  - This study was conducted to compare the mean preference scores for orthodontic
      treatment need, considering the chin position, amongst orthodontists, orthodontic
      patients and their parents. Male and female profile silhouettes were prepared by
      changing their chin prominence using Adobe Photoshop 7 with zero degree meridian
      as line of reference. Rating of these silhouettes was done by the three groups of
      raters (orthodontists, orthodontic patients and their parents) on a scale of four
      with one being no need of treatment and four being severe need of treatment.
      There was a statistically significant difference seen amongst orthodontists and
      the orthodontic patients and also amongst the orthodontist and the orthodontic
      patient's parents for the 2mm and 4mm chin position with orthodontists scoring a
      higher need of treatment as compared to the patients and parents.

PMID- 29467091
TI  - Errata.

PMID- 29467092
TI  - The Effect of Computer-Assisted Reporting on Interreader Variability of Lumbar
      Spine MRI Degenerative Findings: Five Readers With 30 Disc Levels.
AB  - PURPOSE: The aim of this study was to assess differences in interreader
      variability among radiologists after the implementation of a computer-assisted
      reporting (CAR) tool for the interpretation of degenerative disc disease on
      lumbar spine MRI. METHODS: Thirty lumbar spine MRI examinations were selected
      from the radiology database. Five fellowship-trained musculoskeletal radiologists
      evaluated each L4-L5 disc in a blinded fashion and reported the findings using a
      traditional free dictation approach. One month later, they reinterpreted the same
      discs using a web browser-based CAR tool in the same blinded fashion. The degrees
      of central canal stenosis, neural foraminal stenosis, and facet joint
      osteoarthritis; presence or absence of lateral recess stenosis; types of disc
      bulge or herniation; and herniation location using both methods were recorded.
      Percentage disagreement among the radiologists for each variable was calculated
      and compared using the Wilcoxon signed rank test. RESULTS: There was a
      statistically significant decrease among the five radiologists in percentage
      disagreement for neural foraminal stenosis (46% versus 35%, P = .0146) and facet
      joint osteoarthritis (45% and 22%, P < .0001) for reports created by free
      dictation compared with those created using the CAR tool. There was no
      statistically significant difference in interreader variability for the
      assessment of central canal stenosis, lateral recess effacement, disc herniation,
      disc bulge, or herniation location. CONCLUSIONS: Implementation of a CAR tool for
      the interpretation of degenerative changes on lumbar spine MRI decreases
      interreader variability in the assessment of neural foraminal stenosis and facet
      joint osteoarthritis.

PMID- 29467093
TI  - Objective Evaluation of CT Time Efficiency in Acute Stroke Response.

PMID- 29467094
TI  - Motor fluctuations and levodopa-induced dyskinesias in dopa-responsive dystonia.

PMID- 29467095
TI  - Diabetes status is linked to low health literacy: Implications for health system.

PMID- 29467096
TI  - Predictive effect of hyperuricemia on left atrial stasis in non-valvular atrial
      fibrillation patients.
AB  - OBJECTIVES: To investigate the relationship between hyperuricemia and left atrial
      thrombus (LAT)/spontaneous echo contrast (SEC) and to determine the predictive
      value of hyperuricemia in non-valvular (NV) atrial fibrillation (AF) patients.
      METHODS: The study retrospectively reviewed 1198 consecutive patients (male 801,
      female 397, and mean age of 56.84 +/- 12.22) who were diagnosed with AF and
      accepted transesophageal echocardiography (TEE) prior to catheter ablation,
      appendage occlusion and electrical cardioversion using a single-center database.
      The clinical baseline characteristics were collected from medical record review
      and analyzed. Patients were categorized into an LAT/SEC group and a normal group.
      RESULTS: According to the TEE examination, there were 97 (8.1%) patients with
      abnormality; of these, 49 were with LAT and 48 with SEC. The mean serum uric acid
      (SUA) level and hyperuricemia proportion were markedly higher in patients with
      LAT/SEC. The significant predictive effect was observed in the SUA level (OR =
      1.006) and hyperuricemia (OR = 2.04). After adjustment for persistent/permanent
      AF, age, gender, LA dimension > 40 mm, previous stroke, hypertension and
      diabetes, the SUA level (OR = 1.004) and hyperuricemia (OR = 1.69) were
      independent predictors for LAT/SEC. The SUA level (OR = 1.004) and hyperuricemia
      (OR = 1.69) were independent predictors for LAT/SEC, Further subgroup analysis in
      different CHA2DS2-VASc categories, it might be helpful to refine the LAT/SEC risk
      via combination area CHA2DS2-VASc score and hyperuricemia, especially in those
      with CHA2DS2-VASc score < 2. CONCLUSIONS: The SUA level and hyperuricemia
      proportion are closely associated with LA stasis. Hyperuricemia might
      independently predict and refine LA stasis risk among NVAF patients, especially
      in those with CHA2DS2-VASc score < 2.

PMID- 29467097
TI  - Vasovagal responses during cryoballoon pulmonary vein isolation in paroxysmal
      atrial fibrillation predict favorable mid-term outcomes.
AB  - BACKGROUND: Vasovagal responses (VR) encountered during radiofrequency pulmonary
      vein isolation (PVI) in paroxysmal atrial fibrillation (PAF) suggest ablation of
      the atrial tissue subjacent to the ganglionic plexi (GP) and confer durability of
      PVI. OBJECTIVE: We hypothesized that VR during cryoballoon PVI (CB-PVI) in PAF
      can predict mid-term AF recurrence. METHODS: We enrolled 39 patients who
      underwent PVI using 2nd generation cryoballoon for PAF from November 2014 to July
      2016. We evaluated the long term outcomes for those who had VR during index
      procedure. RESULTS: A total of 39 patients (76% male, mean age 57 +/- 9 years)
      underwent CB-PVI for PAF and 66.67% (26/39) had VR. VR was frequently observed in
      the LSPV (100%), followed by RSPV (64%), LIPV (60%), and less frequently, RIPV
      (28%). Overall, the mean difference in the HR and SBP, and the relative
      differences in the HR and SBP were observed during CB-PVI in the LSPV (mean
      difference in HR, p < 0.001; mean difference in SBP, p < 0.001; relative
      difference in HR, p < 0.001); relative difference in SBP, p < 0.001). After PVI,
      22/26 (84.62%) and 5/13 (38.46%) of patients in the VR and NVR group,
      respectively, maintained SR at 14 +/- 6 months follow-up. The Kaplan-Meier
      analysis showed statistical difference in favor of patients with VR during CB-PVI
      (log rank p < 0.01) with a better mid-term outcome. CONCLUSION: In a small cohort
      of patients, VR during CB-PVI in PAF is a surrogate marker for ablation of atrial
      tissue subjacent to the GP and predicts a favorable mid-term outcome for AF
      recurrence.

PMID- 29467099
TI  - !PrEP Ya! Latin America wants PrEP, and Brazil leads the way.

PMID- 29467098
TI  - Retention, engagement, and adherence to pre-exposure prophylaxis for men who have
      sex with men and transgender women in PrEP Brasil: 48 week results of a
      demonstration study.
AB  - BACKGROUND: PrEP Brasil was a demonstration study to assess feasibility of daily
      oral tenofovir diphosphate disoproxil fumarate plus emtricitabine provided at no
      cost to men who have sex with men (MSM) and transgender women at high risk for
      HIV within the Brazilian public health system. We report week 48 pre-exposure
      prophylaxis (PrEP) retention, engagement, and adherence, trends in sexual
      behaviour, and incidence of HIV and sexually transmitted infections in this study
      cohort. METHODS: PrEP Brasil was a 48 week, open-label, demonstration study that
      assessed PrEP delivery at three referral centres for HIV prevention and care in
      Rio de Janeiro, Brazil (Fundacao Oswaldo Cruz), and Sao Paulo, Brazil
      (Universidade de Sao Paulo and Centro de Referencia e Treinamento em DST e AIDS).
      Eligible participants were MSM and transgender women who were HIV negative, aged
      at least 18 years, resident in Rio de Janeiro or Sao Paulo, and reported one or
      more sexual risk criteria in the previous 12 months (eg, condomless anal sex with
      two or more partners, two or more episodes of anal sex with an HIV-infected
      partner, or history of sexually transmitted infection [STI] diagnosis).
      Participants were seen at weeks 4, 12, 24, 36, and 48 for PrEP provision,
      clinical and laboratory evaluation, and HIV testing. Computer-assisted self
      interviews were also done at study visits 12, 24, 36, and 48, and assessed sexual
      behaviour and drug use. PrEP retention was defined by attendance at the week 48
      visit, PrEP engagement was an ordinal five-level variable combining presence at
      the study visit and drug concentrations, and PrEP adherence was evaluated by
      measuring tenofovir diphosphate concentrations in dried blood spots. Logistic
      regression models were used to quantify the association of variables with high
      adherence (>=4 doses per week). The study is registered with ClinicalTrials.gov,
      number NCT01989611. FINDINGS: Between April 1, 2014, and July 8, 2016, 450
      participants initiated PrEP, 375 (83%) of whom were retained until week 48. At
      week 48, 277 (74%) of 375 participants had protective drug concentrations
      consistent with at least four doses per week: 183 (82%) of 222 participants from
      Sao Paulo compared with 94 (63%) of 150 participants from Rio de Janeiro
      (adjusted odds ratio 1.88, 95% CI 1.06-3.34); 119 (80%) of 148 participants who
      reported sex with HIV-infected partners compared with 158 (70%) of 227
      participants who did not (1.78, 1.03-3.08); 67 (87%) of 77 participants who used
      stimulants compared with 210 (71%) of 298 participants who did not (2.23, 1.02
      4.92); and 232 (80%) of 289 participants who had protective concentrations of
      tenofovir disphosphate at week 4 compared with 42 (54%) of 78 participants who
      did not (3.28, 1.85-5.80). Overall, receptive anal sex with the last three
      partners increased from 45% at enrolment to 49% at week 48 (p=0.17), and the mean
      number of sexual partners in the previous 3 months decreased from 11.4 (SD 28.94)
      at enrolment to 8.3 (19.55) at week 48 (p<0.0013). Two individuals seroconverted
      during follow-up (HIV incidence 0.51 per 100 person-years, 95% CI 0.13-2.06);
      both of these patients had undetectable tenofovir concentrations at
      seroconversion. INTERPRETATION: Our results support the effectiveness and
      feasibility of PrEP in a real-world setting. Offering PrEP at public health-care
      clinics in a middle-income setting can retain high numbers of participants and
      achieve high levels of adherence without risk compensation in the investigated
      populations. FUNDING: Brazilian Ministry of Health, Conselho Nacional de
      Desenvolvimento Cientifico e Tecnologico, Secretaria de Vigilancia em Saude,
      Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro,
      and Fundacao de Amparo a Pesquisa do Estado de Sao Paulo.

PMID- 29467101
TI  - Ultrasound screening for complications in twin pregnancy.
AB  - In the decades since the introduction of ultrasound into routine obstetric
      practice, the advantages of ultrasound have moved beyond the simple ability to
      identify multiple pregnancies antenatally to the possibility of screening them
      for fetal anomalies, pre-eclampsia, preterm birth, and the complications specific
      to monochorionic pregnancies. Screening studies have often excluded twins because
      physiological differences impact on the validity and sensitivity of the screening
      tests in routine use in singletons, and therefore, the evidence of screening
      performance in multiple pregnancy lags behind the evidence from singleton
      pregnancies. In general, most pregnancy complications are more common in twin
      pregnancy, but screening tests are less accurate or well validated. In this
      review article we present the current state of the evidence and avenues for
      future research relating to the use of ultrasound and screening for complications
      in twin pregnancies, including the monochorionicity-related pathologies, such as
      twin-twin transfusion syndrome, selective growth restriction, twin anaemia
      polycythaemia sequence and twin reversed arterial perfusion sequence.

PMID- 29467100
TI  - Epileptogenesis in neonatal brain.
AB  - Epilepsy is a chronic neurological disorder affecting 65 million people
      worldwide. The etiologies of seizures can often be identified as genetic,
      metabolic, structural, immunologic or infectious, but in many cases the cause is
      unknown with the current diagnostic tools. Epileptogenesis is a process during
      which genetic or other acquired etiologies/insults lead to functional,
      structural, or network reorganization changes in the brain that may lead to the
      development of, or progression of, spontaneous seizures. During development,
      there are continuous changes in the structure, function, and network operation
      that also show sex specificity, which may alter the mechanisms underlying the
      generation of seizures (ictogenesis) and epileptogenesis. Understanding the
      mechanisms of early life epileptogenesis will enable the development of
      rationally designed age- and sex-appropriate therapies that would improve the
      overall quality of patients' lives. Here, we discuss some of these processes that
      may affect seizure generation and epileptogenesis in the neonatal brain.

PMID- 29467102
TI  - Acute symptomatic neonatal seizures in preterm neonates: etiologies and
      treatments.
AB  - Acute symptomatic neonatal seizures in preterm newborns are a relevant clinical
      challenge due to the presence of many knowledge gaps. Etiology-wise, acute
      symptomatic seizures have an age-specific epidemiology, with intraventricular
      hemorrhage and its complications representing the first cause in extremely and
      very preterm neonates, whereas other etiologies have similar occurrence rates as
      in full-term infants. Specific treatment strategies for the premature neonates
      are not yet available. Studies suggest a similarly low response rate with even
      more unfavorable prognosis than in full-term infants. Pharmacodynamic and
      pharmacokinetic changes are likely under way during the preterm period, with the
      potential to affect both effectiveness and safety of antiepileptic drugs in these
      patients. However, due to the lack of clear evidence to guide prioritization of
      second-line drugs, off-label medications are frequently indicated by review
      papers and flow-charts, and are prescribed in clinical practice. We therefore
      conclude by exploring potential future lines of research.

PMID- 29467103
TI  - Designing a trial for neonatal seizure treatment.
AB  - Neonatal seizures are widely considered a neurological emergency with a need for
      prompt treatment, yet they are known to present a highly elusive target for
      bedside clinicians. Recent studies have suggested that the design of a neonatal
      seizure treatment trial will profoundly influence the sample size, which may
      readily increase to hundreds or even thousands as the achieved effect size
      diminishes to clinical irrelevance. The self-limiting and rapidly resolving
      nature of neonatal seizures diminishes the measurable treatment effect every hour
      after seizure onset and any effect may potentially be confused with spontaneous
      resolution, precluding the value of many observational studies. The large
      individual variability in seizure occurrence over time and between etiologies
      challenges group comparisons, while the absence of clinical signs mandates
      quantification of seizure occurrence with continuous multi-channel EEG
      monitoring. A biologically sound approach that views neonatal seizures as a
      functional cot-side biomarker rather than an object to treat can overcome these
      challenges.

PMID- 29467104
TI  - Estimating Acute Cardiovascular Effects of Ambient PM2.5 Metals.
AB  - BACKGROUND: Few epidemiologic studies have investigated health effects of water
      soluble fractions of PM2.5 metals, the more biologically accessible fractions of
      metals, in their attempt to identify health-relevant components of ambient PM2.5.
      OBJECTIVES: In this study, we estimated acute cardiovascular effects of PM2.5
      components in an urban population, including a suite of water-soluble metals that
      are not routinely measured at the ambient level. METHODS: Ambient concentrations
      of criteria gases, PM2.5, and PM2.5 components were measured at a central monitor
      in Atlanta, Georgia, during 1998-2013, with some PM2.5 components only measured
      during 2008-2013. In a time-series framework using Poisson regression, we
      estimated associations between these pollutants and daily counts of emergency
      department (ED) visits for cardiovascular diseases in the five-county Atlanta
      area. RESULTS: Among the PM2.5 components we examined during 1998-2013, water
      soluble iron had the strongest estimated effect on cardiovascular outcomes
      [RR=1.012 (95% CI: 1.005, 1.019), per interquartile range increase (20.46ng/m3)].
      The associations for PM2.5 and other PM2.5 components were consistent with the
      null when controlling for water-soluble iron. Among PM2.5 components that were
      only measured during 2008-2013, water-soluble vanadium was associated with
      cardiovascular ED visits [RR=1.012 (95% CI: 1.000, 1.025), per interquartile
      range increase (0.19ng/m3)]. CONCLUSIONS: Our study suggests cardiovascular
      effects of certain water-soluble metals, particularly water-soluble iron. The
      observed associations with water-soluble iron may also point to certain aspects
      of traffic pollution, when processed by acidifying sulfate, as a mixture harmful
      for cardiovascular health. https://doi.org/10.1289/EHP2182.

PMID- 29467105
TI  - Metal Concentrations in e-Cigarette Liquid and Aerosol Samples: The Contribution
      of Metallic Coils.
AB  - BACKGROUND: Electronic cigarettes (e-cigarettes) generate an aerosol by heating a
      solution (e-liquid) with a metallic coil. Whether metals are transferred from the
      coil to the aerosol is unknown. OBJECTIVE: Our goal was to investigate the
      transfer of metals from the heating coil to the e-liquid in the e-cigarette tank
      and the generated aerosol. METHODS: We sampled 56 e-cigarette devices from daily
      e-cigarette users and obtained samples from the refilling dispenser, aerosol, and
      remaining e-liquid in the tank. Aerosol liquid was collected via deposition of
      aerosol droplets in a series of conical pipette tips. Metals were reported as
      mass fractions (MUg/kg) in liquids and converted to mass concentrations (mg/m3)
      for aerosols. RESULTS: Median metal concentrations (MUg/kg) were higher in
      samples from the aerosol and tank vs. the dispenser (all p<0.001): 16.3 and 31.2
      vs. 10.9 for Al; 8.38 and 55.4 vs. <0.5 for Cr; 68.4 and 233 vs. 2.03 for Ni;
      14.8 and 40.2 vs. 0.476 for Pb; and 515 and 426 vs. 13.1 for Zn. Mn, Fe, Cu, Sb,
      and Sn were detectable in most samples. Cd was detected in 0.0, 30.4, and 55.1%
      of the dispenser, aerosol, and tank samples respectively. Arsenic was detected in
      10.7% of dispenser samples (median 26.7MUg/kg) and these concentrations were
      similar in aerosol and tank samples. Aerosol mass concentrations (mg/m3) for the
      detected metals spanned several orders of magnitude and exceeded current health
      based limits in close to 50% or more of the samples for Cr, Mn, Ni, and Pb.
      CONCLUSIONS: Our findings indicate that e-cigarettes are a potential source of
      exposure to toxic metals (Cr, Ni, and Pb), and to metals that are toxic when
      inhaled (Mn and Zn). Markedly higher concentrations in the aerosol and tank
      samples versus the dispenser demonstrate that coil contact induced e-liquid
      contamination. https://doi.org/10.1289/EHP2175.

PMID- 29467106
TI  - Ultrafine and Fine Particle Number and Surface Area Concentrations and Daily
      Cause-Specific Mortality in the Ruhr Area, Germany, 2009-2014.
AB  - BACKGROUND: Although epidemiologic studies have shown associations between
      particle mass and daily mortality, evidence on other particle metrics is weak.
      OBJECTIVES: We investigated associations of size-specific particle number
      concentration (PNC) and lung-deposited particle surface area concentration (PSC)
      with cause-specific daily mortality in contrast to PM10. METHODS: We used time
      series data (March 2009-December 2014) on daily natural, cardiovascular, and
      respiratory mortality (NM, CVM, RM) of three adjacent cities in the Ruhr Area,
      Germany. Size-specific PNC (electric mobility diameter of 13.3-750 nm), PSC, and
      PM10 were measured at an urban background monitoring site. In single- and
      multipollutant Poisson regression models, we estimated percentage change (95%
      confidence interval) [% (95% CI)] in mortality per interquartile range (IQR) in
      exposure at single-day (0-7) and aggregated lags (0-1, 2-3, 4-7), accounting for
      time trend, temperature, humidity, day of week, holidays, period of seasonal
      population decrease, and influenza. RESULTS: PNC100-750 and PSC were highly
      correlated and had similar immediate (lag0-1) and delayed (lag4-7) associations
      with NM and CVM, for example, 1.12% (95% CI: 0.09, 2.33) and 1.56% (95% CI: 0.22,
      2.92) higher NM with IQR increases in PNC100-750 at lag0-1 and lag4-7,
      respectfully, which were slightly stronger then associations with IQR increases
      in PM10. Positive associations between PNC and NM were strongest for accumulation
      mode particles (PNC 100-500 nm), and for larger UFPs (PNC 50-100 nm).
      Associations between NM and PNC<100 changed little after adjustment for O3 or
      PM10, but were more sensitive to adjustment for NO2. CONCLUSION: Size-specific
      PNC (50-500 nm) and lung-deposited PSC were associated with natural and
      cardiovascular mortality in the Ruhr Area. Although associations were similar to
      those estimated for an IQR increase in PM10, particle number size distributions
      can be linked to emission sources, and thus may be more informative for potential
      public health interventions. Moreover, PSC could be used as an alternative metric
      that integrates particle size distribution as well as deposition efficiency.
      https://doi.org/10.1289/EHP2054.

PMID- 29467107
TI  - Associations between Personal Care Product Use Patterns and Breast Cancer Risk
      among White and Black Women in the Sister Study.
AB  - BACKGROUND: Many personal care products include chemicals that might act as
      endocrine disruptors and thus increase the risk of breast cancer. OBJECTIVE: We
      examined the association between usage patterns of beauty, hair, and skin-related
      personal care products and breast cancer incidence in the Sister Study, a
      national prospective cohort study (enrollment 2003-2009). METHODS: Non-Hispanic
      black (4,452) and white women (n=42,453) were examined separately using latent
      class analysis (LCA) to identify groups of individuals with similar patterns of
      self-reported product use in three categories (beauty, skin, hair). Multivariable
      Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95%
      confidence intervals (CIs) for associations between product use and breast cancer
      incidence. RESULTS: A total of 2,326 women developed breast cancer during follow
      up (average follow-up=5.4y). Among black women, none of the latent class hazard
      ratios was elevated, but there were <100 cases in any category, limiting power.
      Among white women, those classified as "moderate" and "frequent" users of beauty
      products had increased risk of breast cancer relative to "infrequent" users
      [HR=1.13 (95% CI: 1.00, 1.27) and HR=1.15 (95% CI: 1.02, 1.30), respectively].
      Frequent users of skincare products also had increased risk of breast cancer
      relative to infrequent users [HR=1.13 (95% CI: 1.00, 1.29)]. None of the hair
      product classes was associated with increased breast cancer risk. The
      associations with beauty and skin products were stronger in postmenopausal women
      than in premenopausal women, but not significantly so. CONCLUSIONS: This work
      generates novel hypotheses about personal care product use and breast cancer
      risk. Whether these results are due to specific chemicals or to other correlated
      behaviors needs to be evaluated. https://doi.org/10.1289/EHP1480.

PMID- 29467109
TI  - What's in the Mix? Improving Risk Assessment of Food Contact Materials.

PMID- 29467108
TI  - The Association of Long-Term Exposure to Particulate Matter Air Pollution with
      Brain MRI Findings: The ARIC Study.
AB  - BACKGROUND: Increasing evidence links higher particulate matter (PM) air
      pollution exposure to late-life cognitive impairment. However, few studies have
      considered associations between direct estimates of long-term past exposures and
      brain MRI findings indicative of neurodegeneration or cerebrovascular disease.
      OBJECTIVE: Our objective was to quantify the association between brain MRI
      findings and PM exposures approximately 5 to 20 y prior to MRI in the
      Atherosclerosis Risk in Communities (ARIC) study. METHODS: ARIC is based in four
      U.S. sites: Washington County, Maryland; Minneapolis suburbs, Minnesota; Forsyth
      County, North Carolina; and Jackson, Mississippi. A subset of ARIC participants
      underwent 3T brain MRI in 2011-2013 (n=1,753). We estimated mean exposures to PM
      with an aerodynamic diameter less than 10 or 2.5MUm (PM10 and PM2.5) in 1990
      1998, 1999-2007, and 1990-2007 at the residential addresses of eligible
      participants with MRI data. We estimated site-specific associations between PM
      and brain MRI findings and used random-effect, inverse variance-weighted meta
      analysis to combine them. RESULTS: In pooled analyses, higher mean PM2.5 and PM10
      exposure in all time periods were associated with smaller deep-gray brain
      volumes, but not other MRI markers. Higher PM2.5 exposures were consistently
      associated with smaller total and regional brain volumes in Minnesota, but not
      elsewhere. CONCLUSIONS: Long-term past PM exposure in was not associated with
      markers of cerebrovascular disease. Higher long-term past PM exposures were
      associated with smaller deep-gray volumes overall, and higher PM2.5 exposures
      were associated with smaller brain volumes in the Minnesota site. Further work is
      needed to understand the sources of heterogeneity across sites.
      https://doi.org/10.1289/EHP2152.

PMID- 29467110
TI  - Erratum: "Estimated Changes in Life Expectancy and Adult Mortality Resulting from
      Declining PM2.5 Exposures in the Contiguous United States: 1980-2010".
AB  - [This corrects the article DOI: https://doi.org/10.1289/EHP507.].

PMID- 29467111
TI  - Erratum: "Traditional Ecological Knowledge: A Different Perspective on
      Environmental Health".
AB  - [This corrects the article DOI: https://doi.org/10.1289/EHP2391.].

PMID- 29467112
TI  - Interobserver agreement between senior radiology resident, neuroradiology fellow,
      and experienced neuroradiologist in the rating of Alberta Stroke Program Early
      Computed Tomography Score (ASPECTS).
AB  - PURPOSE: The distribution of ischemic changes caused by infarction of the middle
      cerebral artery (MCA) territories is usually measured using the Alberta Stroke
      Program Early Computed Tomography Score (ASPECTS). The first interpreter of the
      brain computed tomography (CT) in the emergency department is the on-call
      radiology resident. The primary objective of this study was to describe the
      agreement of the ASPECTS performed retrospectively by the resident compared with
      expert raters. The second objective was to ascertain the appropriate window
      setting for early detection of acute ischemic stroke and good interobserver
      agreement between the interpreters. METHODS: We identified consecutive patients
      presenting with hemiparesis or aphasia at the emergency department who underwent
      brain CT and CT angiography. Each scan was rated using ASPECTS by senior
      radiology resident, neuroradiology fellow, and later by consensus between two
      expert raters. Statistical analysis included determination of Cohen's kappa
      (kappa) coefficient and intraclass correlation coefficient (ICC). RESULTS: A
      total of 43 patients met our study criteria. Interobserver agreements for ASPECTS
      varied from 0.486 to 0.678 in Cohen's kappa coefficient between consensus of two
      neuroradiologists and a neuroradiology fellow, and from 0.198 to 0.491 for
      consensus between two neuroradiologists and a senior radiology resident. ICC
      among three raters (expert consensus, neuroradiology fellow, and senior radiology
      resident), was very good when 8 HU window width and 32 HU center level setting
      was used. CONCLUSION: ASPECTS varied among raters. However, when using a narrowed
      window setting for interpretation, interobserver agreement improved.

PMID- 29467113
TI  - Accuracy of the ADNEX MR scoring system based on a simplified MRI protocol for
      the assessment of adnexal masses.
AB  - PURPOSE: We aimed to evaluate the ADNEX MR scoring system for the prediction of
      adnexal mass malignancy, using a simplified magnetic resonance imaging (MRI)
      protocol. METHODS: In this prospective study, 200 patients with 237 adnexal
      masses underwent MRI between February 2014 and February 2016 and were followed
      until February 2017. Two radiologists calculated ADNEX MR scores using an MRI
      protocol with a simplified dynamic study, not a high temporal resolution study,
      as originally proposed. Sensitivity, specificity, positive and negative
      predictive values, likelihood ratios, and the area under the receiver operating
      characteristic curve were calculated (cutoff for malignancy, score >= 4). The
      reference standard was histopathologic diagnosis or imaging findings during >12
      months of follow-up. RESULTS: Of 237 lesions, 79 (33.3%) were malignant. The
      ADNEX MR scoring system, using a simplified MRI protocol, showed 94.9% (95%
      confidence interval [CI], 87.5%-98.6%) sensitivity and 97.5% (95% CI, 93.6%
      99.3%) specificity in malignancy prediction; it was thus highly accurate, like
      the original system. The level of interobserver agreement on simplified scoring
      was high (kappa = 0.91). CONCLUSION: In a tertiary cancer center, the ADNEX MR
      scoring system, even based on a simplified MRI protocol, performed well in the
      prediction of malignant adnexal masses. This scoring system may enable the
      standardization of MRI reporting on adnexal masses, thereby improving
      communication between radiologists and gynecologists.

PMID- 29467114
TI  - Adrenal venous sampling: the learning curve of a single interventionalist with
      282 consecutive procedures.
AB  - PURPOSE: Primary aldosteronism (PA) is a common cause of secondary hypertension.
      Adrenal venous sampling (AVS) is the gold standard for assessing laterality of
      PA, which is of paramount importance to decide adequate treatment. AVS is a
      technically complicated procedure with success rates ranging between 30% and 96%.
      The aim of this study was to investigate the success rate of AVS over time,
      performed by a single interventionalist. METHODS: This was a retrospective study
      based on consecutive AVS procedures performed by a single operator between
      September 2005 and June 2016. Data on serum concentrations of aldosterone and
      cortisol from right and left adrenal vein, inferior vena cava, and peripheral
      vein were collected and selectivity index (SI) calculated. Successful AVS was
      defined as SI > 5. RESULTS: In total, 282 AVS procedures were performed on 269
      patients, 168 men (62%) and 101 women (38%), with a mean age of 55+/-11 years
      (range, 26-78 years). Out of 282 AVS procedures, 259 were successful, giving an
      overall success rate of 92%. The most common reason for failure was inability to
      localize the right adrenal vein (n=16; 76%). The success rates were 63%, 82%, and
      94% during the first, second, and third years, respectively. During the last 8
      years the success rate was 95%, and on average 27 procedures were performed
      annually. CONCLUSION: Satisfactory AVS success rate was achieved after
      approximately 36 procedures and satisfactory success rate was maintained by
      performing approximately 27 procedures annually. AVS should be limited to few
      operators that perform sufficiently large number of procedures to achieve, and
      maintain, satisfactory AVS success rate.

PMID- 29467115
TI  - The pancreatic and extrapancreatic manifestations of IgG4-related disease.
AB  - The association between immunoglobulin IgG4 and autoimmune pancreatitis was first
      shown in 2001. Since then many previously established fibrosclerotic diseases
      demonstrating synchronous or metachronous multiorgan involvement have been
      included within the ambit of IgG4-related disease. Diagnostic criteria have been
      proposed involving 1) serum IgG4 level elevated beyond 135 mg/dL, 2) IgG4+ to
      IgG+ plasma cell ratio > 40% and >10 IgG4+ cells per high power field of biopsy
      sample and 3) a constellation of imaging features which involve a variety of
      organ systems. We present a pictorial essay demonstrating the spectrum of imaging
      findings for IgG4-related disease, including dacryosialadenitis, variety of renal
      lesions, tumefactive thickening of the extraocular muscles and orbital nerve,
      sclerosing cholangitis, and type I pancreatitis. Imaging plays an important role
      in diagnosis, screening for multiorgan involvement, and follow-up of the disease.

PMID- 29467116
TI  - N-butyl cyanoacrylate embolotherapy: techniques, complications, and management.
AB  - The purpose of this article is to describe acute complications associated with
      adhesive cyanoacrylate deposition in the peripheral circulation and their
      management. Despite best efforts, n-butyl cyanoacrylate glue embolization is
      inherently unpredictable and complications do occur. An understanding of
      preparation techniques that minimize adverse event rates and the technical
      skillset required to manage complications are necessary for the safe and
      efficient use of liquid embolic agents.

PMID- 29467117
TI  - The Effects of Bougie Diameters on Tissue Oxygen Levels After Sleeve Gastrectomy:
      A Randomized Experimental Trial
AB  - Background: Staple-line leak is the most frightening complication of laparoscopic
      sleeve gastrectomy and several predisposing factors such as using improper staple
      sizes regardless of gastric wall thickness, narrower bougie diameter and ischemia
      of the staple line are asserted. Aims: To evaluate the effects of different
      bougie diameters on tissue oxygen partial pressure at the esophagogastric
      junction after sleeve gastrectomy. Study Design: A randomized and controlled
      animal experiment with 1:1:1:1 allocation ratio. Methods: Thirty-two male Wistar
      Albino rats were randomly divided into 4 groups of 8 each. While 12-Fr bougies
      were used in groups 1 and 3, 8-Fr bougies were used in groups 2 and 4. Fibrin
      sealant application was also carried out around the gastrectomy line after sleeve
      gastrectomy in groups 3 and 4. Burst pressure of gastrectomy line, tissue oxygen
      partial pressure and hydroxyproline levels at the esophagogastric junction were
      measured and compared among groups. Results: Mortality was detected in 2 out of
      32 rats (6.25%) and one of them was in group 2 and the cause of this mortality
      was gastric leak. Gastric leak was detected in 2 out of 32 rats (6.25%). There
      was no significant difference in terms of burst pressures, tissue oxygen partial
      pressure and tissue hydroxyproline levels among the 4 groups. Conclusion: The use
      of narrower bougie along with fibrin sealant has not had a negative effect on
      tissue perfusion and wound healing.

PMID- 29467118
TI  - Type 2 Diabetes Education and Support in a Virtual Environment: A Secondary
      Analysis of Synchronously Exchanged Social Interaction and Support.
AB  - BACKGROUND: Virtual environments (VEs) facilitate interaction and support among
      individuals with chronic illness, yet the characteristics of these VE
      interactions remain unknown. OBJECTIVE: The objective of this study was to
      describe social interaction and support among individuals with type 2 diabetes
      (T2D) who interacted in a VE. METHODS: Data included VE-mediated synchronous
      conversations and text-chat and asynchronous emails and discussion board posts
      from a study that facilitated interaction among individuals with T2D and diabetes
      educators (N=24) in 2 types of sessions: education and support. RESULTS: VE
      interactions consisted of communication techniques (how individuals interact in
      the VE), expressions of self-management (T2D-related topics), depth
      (personalization of topics), and breadth (number of topics discussed).
      Individuals exchanged support more often in the education (723/1170, 61.79%) than
      in the support (406/1170, 34.70%) sessions or outside session time (41/1170,
      3.50%). Of all support exchanges, 535/1170 (45.73%) were informational, 377/1170
      (32.22%) were emotional, 217/1170 (18.55%) were appraisal, and 41/1170 (3.50%)
      were instrumental. When comparing session types, education sessions predominately
      provided informational support (357/723, 49.4%), and the support sessions
      predominately provided emotional (159/406, 39.2%) and informational (159/406,
      39.2%) support. CONCLUSIONS: VE-mediated interactions resemble those in face-to
      face environments, as individuals in VEs engage in bidirectional exchanges with
      others to obtain self-management education and support. Similar to face-to-face
      environments, individuals in the VE revealed personal information, sought
      information, and exchanged support during the moderated education sessions and
      unstructured support sessions. With this versatility, VEs are able to contribute
      substantially to support for those with diabetes and, very likely, other chronic
      diseases.

PMID- 29467119
TI  - Pre-Exposure Prophylaxis YouTube Videos: Content Evaluation.
AB  - BACKGROUND: Antiretroviral (ARV) medicines reduce the risk of transmitting the
      HIV virus and are recommended as daily pre-exposure prophylaxis (PrEP) in
      combination with safer sex practices for HIV-negative individuals at a high risk
      for infection, but are underused in HIV prevention. Previous literature suggests
      that YouTube is extensively used to share health information. While pre-exposure
      prophylaxis (PrEP) is a novel and promising approach to HIV prevention, there is
      limited understanding of YouTube videos as a source of information on PrEP.
      OBJECTIVE: The objective of this study was to describe the sources,
      characteristics, and content of the most widely viewed PrEP YouTube videos
      published up to October 1, 2016. METHODS: The keywords "pre-exposure prophylaxis"
      and "Truvada" were used to find 217 videos with a view count >100. Videos were
      coded for source, view count, length, number of comments, and selected aspects of
      content. Videos were also assessed for the most likely target audience. RESULTS:
      The total cumulative number of views was >2.3 million, however, a single Centers
      for Disease Control and Prevention video accounted for >1.2 million of the total
      cumulative views. A great majority (181/217, 83.4%) of the videos promoted the
      use of PrEP, whereas 60.8% (132/217) identified the specific target audience. In
      contrast, only 35.9% (78/217) of the videos mentioned how to obtain PrEP, whereas
      less than one third addressed the costs, side effects, and safety aspects
      relating to PrEP. Medical and academic institutions were the sources of the
      largest number of videos (66/217, 30.4%), followed by consumers (63/217, 29.0%),
      community-based organizations (CBO; 48/217, 22.1%), and media (40/217, 18.4%).
      Videos uploaded by the media sources were more likely to discuss the cost of PrEP
      (P<.001), whereas the use of PrEP was less likely to be promoted in videos
      uploaded by individual consumers (P=.002) and more likely to be promoted in
      videos originated by CBOs (P=.009). The most common target audience for the
      videos was gay and bisexual men. CONCLUSIONS: YouTube videos can be used to share
      reliable PrEP information with individuals. Further research is needed to
      identify the best practices for using this medium to promote and increase PrEP
      uptake.

PMID- 29467120
TI  - Medicaid Becomes the First Third-Party Payer to Cover Passive Remote Monitoring
      for Home Care: Policy Analysis.
AB  - BACKGROUND: Recent years have seen an influx of location-tracking, activity
      monitoring sensors, and Web-cameras to remotely monitor the safety of older
      adults in their homes and to reduce reliance on in-person assistance. The state
      of research on these monitoring technologies leaves open crucial financial,
      social, and ethical cost-benefit questions, which have prevented widespread use.
      Medicaid is now the first large third-party payer in the United States to pay for
      these technologies, and their use is likely to increase as states transition to
      managed long-term services and supports (MLTSS). OBJECTIVES: This is the first
      study to examine how state Medicaid programs are treating passive remote
      monitoring technologies. This study identifies (1) which states allow location
      tracking, sensor systems, and cameras; (2) what policies are in place to track
      their use; (3) what implementation processes and program monitoring mechanisms
      are in place; and (4) what related insights Medicaid program stakeholders would
      like to learn from researchers. METHODS: Interviews were conducted with 43 state,
      federal, and managed care organization (MCO) Medicaid program stakeholders about
      how these technologies are used in state waivers serving community-dwelling older
      adults in 15 states, and what policies are in place to regulate them. The
      interviews were analyzed by the research team using the framework analysis method
      for applied policy research. RESULTS: Two-thirds of the states cover location
      tracking and activity-monitoring sensors and one-third cover cameras, but only 3
      states have specific service categories that allow them to track when they are
      paying for any of these technologies, impeding regulation and understanding of
      their use at the state and federal level. Consideration of ethical and social
      risks is limited, and states struggle to understand which circumstances warrant
      use. They are further challenged by extreme resource restrictions and transitions
      to MLTSS by MCOs inexperienced in serving this growing "high-need, high-cost"
      population. CONCLUSIONS: Decisions about Medicaid reimbursement of technologies
      that have the potential to dramatically alter the way older adults receive
      supportive services are being made without research on their use, social and
      ethical implications, or outcomes. At a minimum, new service categories are
      needed to enable oversight. Participants prioritized 3 research aims to inform
      practice: (1) determine cost-effectiveness; (2) identify what type of information
      beneficiaries want to be generated and whom they want it to be shared with; and
      (3) understand how to support ethical decision making for beneficiaries with
      cognitive impairment. These findings provide direction for future research and
      reveal that greater interaction between policy makers and researchers in this
      field is needed.

PMID- 29467121
TI  - Clinical Feasibility of Continuously Monitored Data for Heart Rate, Physical
      Activity, and Sleeping by Wearable Activity Trackers in Patients with
      Thyrotoxicosis: Protocol for a Prospective Longitudinal Observational Study.
AB  - BACKGROUND: Thyrotoxicosis is a common disease caused by an excess of thyroid
      hormones. The prevalence of thyrotoxicosis about 2% and 70-90% of thyrotoxicosis
      cases are caused by Graves' disease, an autoimmune disease, which has a high
      recurrence rate when treated with antithyroid drugs such as methimazole or
      propylthiouracil. The clinical symptoms and signs of thyrotoxicosis include
      palpitation, weight loss, restlessness, and difficulty sleeping. Although these
      clinical changes in thyrotoxicosis can be detected by currently available
      wearable activity trackers, there have been few trials of the clinical
      application of wearable devices in patients with thyrotoxicosis. OBJECTIVE: The
      aim of this study is to investigate the clinical applicability of wearable device
      generated data to the management of thyrotoxicosis. We are analyzing continuously
      monitored data for heart rate, physical activity, and sleep in patients with
      thyrotoxicosis during their clinical course after treatment. METHODS: Thirty
      thyrotoxic patients and 10 control subjects were enrolled in this study at Seoul
      National University Bundang Hospital. Heart rate, physical activity, and sleep
      are being monitored using a Fitbit Charge HR or Fitbit Charge 2. Clinical data
      including anthropometric measures, thyroid function test, and hyperthyroidism
      symptom scale are recorded. RESULTS: Study enrollment began in December 2016, and
      the intervention and follow-up phases are ongoing. The results of the data
      analysis are expected to be available by September 2017. CONCLUSIONS: This study
      will provide a foundational feasibility trial of the clinical applications of
      biosignal measurements to the differential diagnosis, prediction of clinical
      course, early detection of recurrence, and treatment in patients with
      thyrotoxicosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03009357;
      https://clinicaltrials.gov/ct2/show/NCT03009357 (Archived by WebCite at
      http://www.webcitation.org/6wh4MWPm2).

PMID- 29467122
TI  - Systemic lupus erythematosus presenting to haematology with pancytopenia and
      features of macrophage activation syndrome.

PMID- 29467123
TI  - Successful perioperative management in a patient with factor XI deficiency.
AB  - Factor XI (FXI) deficiency is an autosomal disorder which manifests as bleeding
      of varying severity. While homozygotes typically experience more dramatic
      bleeding symptoms, heterozygotes may experience clinically significant bleeding
      following surgical procedures or trauma, and therefore the condition is not
      purely recessive. The clinical significance of FXI deficiency is complicated in
      that FXI levels do not correlate well with bleeding severity, and in fact the
      bleeding risk is variable even for an individual in response to different
      haemostatic challenges. We present the case of a 74-year-old man of Ashkenazi
      Jewish heritage with a family and personal history of bleeding during surgical
      procedures, who presented with excessive bleeding following total thyroidectomy.
      He was found to have a FXI level of 52% (low normal). Genetic testing revealed
      that he was heterozygous for the c.403G>T mutation. This case demonstrates
      successful work-up and perioperative management of a patient with FXI deficiency.

PMID- 29467124
TI  - Gastric and duodenal ischaemia after transarterial chemoembolisation for
      hepatocellular carcinoma: an unexpected but significant complication.
AB  - Transarterial chemoembolisation (TACE) is commonly used for unresectable
      intermediate-stage hepatocellular carcinoma (HCC). TACE is usually well
      tolerated. We report a case of a patient who presented with a gastrointestinal
      bleed from TACE. A 64-year-old man presented with chronic hepatitis C cirrhosis
      and multifocal bilobar HCC. He had previously undergone multiple TACE sessions,
      radiofrequency ablation and stereotactic body radiation therapy. In the evening
      of his TACE procedure, he developed abdominal pain and haematemesis. An
      oesophagogastroduodenoscopy (OGD) showed non-bleeding oesophageal varices and
      ulcerations in the stomach and duodenum, with pathology demonstrating mucosal
      necrosis. The patient recovered and was discharged on omeprazole. While TACE is
      considered safe with most patients only experiencing postembolisation syndrome,
      vascular complications have been reported. In our patient, OGD revealed
      ulcerations, with biopsies confirming ischaemic ulceration. The likely aetiology
      was seepage of the embolic particles into neighbouring arteries. Patients should
      be carefully selected for TACE and monitored post procedure.

PMID- 29467125
TI  - Cefepime-induced encephalopathy.

PMID- 29467126
TI  - Misunderstanding the goals of animal research.

PMID- 29467127
TI  - Quantitative Analysis of Immune Infiltrates in Primary Melanoma.
AB  - Novel methods to analyze the tumor microenvironment (TME) are urgently needed to
      stratify melanoma patients for adjuvant immunotherapy. Tumor-infiltrating
      lymphocyte (TIL) analysis, by conventional pathologic methods, is predictive but
      is insufficiently precise for clinical application. Quantitative multiplex
      immunofluorescence (qmIF) allows for evaluation of the TME using multiparameter
      phenotyping, tissue segmentation, and quantitative spatial analysis (qSA). Given
      that CD3+CD8+ cytotoxic lymphocytes (CTLs) promote antitumor immunity, whereas
      CD68+ macrophages impair immunity, we hypothesized that quantification and
      spatial analysis of macrophages and CTLs would correlate with clinical outcome.
      We applied qmIF to 104 primary stage II to III melanoma tumors and found that
      CTLs were closer in proximity to activated (CD68+HLA-DR+) macrophages than
      nonactivated (CD68+HLA-DR-) macrophages (P < 0.0001). CTLs were further in
      proximity from proliferating SOX10+ melanoma cells than nonproliferating ones (P
      < 0.0001). In 64 patients with known cause of death, we found that high CTL and
      low macrophage density in the stroma (P = 0.0038 and P = 0.0006, respectively)
      correlated with disease-specific survival (DSS), but the correlation was less
      significant for CTL and macrophage density in the tumor (P = 0.0147 and P =
      0.0426, respectively). DSS correlation was strongest for stromal HLA-DR+ CTLs (P
      = 0.0005). CTL distance to HLA-DR- macrophages associated with poor DSS (P =
      0.0016), whereas distance to Ki67- tumor cells associated inversely with DSS (P =
      0.0006). A low CTL/macrophage ratio in the stroma conferred a hazard ratio (HR)
      of 3.719 for death from melanoma and correlated with shortened overall survival
      (OS) in the complete 104 patient cohort by Cox analysis (P = 0.009) and merits
      further development as a biomarker for clinical application. Cancer Immunol Res;
      6(4); 481-93. (c)2018 AACR.

PMID- 29467128
TI  - Macrophages and CD8+ T Cells Mediate the Antitumor Efficacy of Combined CD40
      Ligation and Imatinib Therapy in Gastrointestinal Stromal Tumors.
AB  - Tyrosine kinase inhibition of gastrointestinal stromal tumors (GIST) is effective
      but typically culminates in resistance and is rarely curative. Immunotherapy has
      potential application to GIST, as we previously showed that T-cell checkpoint
      blockade increases the antitumor effects of imatinib. Here, we showed that
      ligation of CD40 using an agonistic antibody (anti-CD40) activated tumor
      associated macrophages (TAMs) in vivo in a knock-in mouse model of GIST harboring
      a germline mutation in Kit exon 11. Activated TAMs had greater TNFalpha
      production and NFkappaB signaling and directly inhibited tumor cells in vitro
      Anti-CD40 required concomitant therapy with imatinib for efficacy and depended on
      TAMs, and to a lesser extent CD8+ T cells, but not on CD4+ T cells or B cells. In
      an analysis of 50 human GIST specimens by flow cytometry, we found that CD40 was
      expressed on human TAMs and tumor cells yet was downregulated after response to
      imatinib. CD40 ligation did not have a direct inhibitory effect on human GIST
      cells. Our findings provide the rationale for combining anti-CD40 and tyrosine
      kinase inhibition to treat human GIST. Cancer Immunol Res; 6(4); 434-47. (c)2018
      AACR.

PMID- 29467129
TI  - Antiretroviral treatment Long-Term (ALT) cohort: a prospective cohort of 10 years
      of ART-experienced patients in Uganda.
AB  - PURPOSE: Little information is available on patients on antiretroviral treatment
      (ART) after a long-term period from sub-Saharan Africa, with the longest follow
      up and related outcomes being after 10 years on ART. At the Infectious Diseases
      Institute (IDI) (Kampala, Uganda), we set up a cohort of patients already on ART
      for 10 years at the time of enrolment, who will be followed up for additional 10
      years. PARTICIPANTS: A prospective observational cohort of 1000 adult patients
      previously on ART for 10 years was enrolled between May 2014 and September 2015.
      Patients were eligible for enrolment if they were in their consecutive 10th year
      of ART regardless of the combination of drugs for both first- and second-line
      ART. Data were collected at enrolment and all annual study visits. Follow-up
      visits are scheduled once a year for 10 years. Biological samples (packed cells,
      plasma and serum) are stored at enrolment and follow-up visits. FINDINGS TO DATE:
      Out of 1000 patients enrolled, 345 (34.5%) originate from a pre-existing research
      cohort at IDI, while 655 (65.5%) were enrolled from the routine clinic. Overall,
      81% of the patients were on first line at the time of the enrolment in the ART
      long-term cohort, with the more frequent regimen being zidovudine plus lamivudine
      plus nevirapine (44% of the cohort), followed by zidovudine plus lamivudine plus
      efavirenz (22%) and tenofovir plus lamivudine or emtricitabine plus efavirenz
      (10%). At cohort enrolment, viral suppression was defined as HIV-RNA <400
      copies/mL was 95.8%. FUTURE PLANS: Through collaboration with other institutions,
      we are planning several substudies, including the evaluation of the risk for
      cardiovascular diseases, the assessment of bone mineral density, screening for
      liver cirrhosis using fibroscan technology and investigation of drug-drug
      interactions between ART and common drugs used for non-communicable diseases.

PMID- 29467130
TI  - How do time trends in inhospital mortality compare? A retrospective study of
      England and Scotland over 17 years using administrative data.
AB  - OBJECTIVES: To examine the trends in inhospital mortality for England and
      Scotland over a 17-year period to determine whether and if so to what extent the
      time trends differ after controlling for differences in the patients treated.
      DESIGN: Analysis of retrospective administrative hospital data using descriptive
      aggregate statistics of trends in inhospital mortality and estimates of a
      logistic regression model of individual patient-level inhospital mortality
      accounting for patient characteristics, case-mix, and country-specific and year
      specific intercepts. SETTING: Secondary care across all hospitals in England and
      Scotland from 1997 to 2013. POPULATION: Over 190 million inpatient admissions,
      either electively or emergency, in England or Scotland from 1997 to 2013. DATA:
      Hospital Episode Statistics for England and the Scottish Morbidity Record 01 for
      Scotland. MAIN OUTCOME MEASURES: Separately for two admission pathways (elective
      and emergency), we examine aggregate time trends of the proportion of patients
      who die in hospital and a binary variable indicating whether an individual
      patient died in hospital or survived, and how that indicator is influenced by the
      patient's characteristics, the year and the country (England or Scotland) in
      which they were admitted. RESULTS: Inhospital mortality has declined in both
      countries over the period studied, for both elective and emergency admissions,
      but has declined more in England than Scotland. The difference in trend reduction
      is greater for elective admissions. These differences persist after controlling
      for patient characteristics and case-mix. CONCLUSIONS: Comparing data at country
      level suggests questions about the roles performed by or functioning of their
      healthcare systems. We found substantial differences between Scotland and England
      in regard to the trend reductions in inhospital mortality. Hospital resources are
      therefore being deployed increasingly differently over time in these two
      countries for reasons that have yet to be explained.

PMID- 29467131
TI  - HIV/AIDS mortality attributable to alcohol use in South Africa: a comparative
      risk assessment by socioeconomic status.
AB  - OBJECTIVES: To quantify HIV/AIDS mortality attributable to alcohol use in the
      adult general population of South Africa in 2012 by socioeconomic status (SES).
      DESIGN: Comparative risk assessment based on secondary individual data, aggregate
      data and risk relations reported in the literature. SETTING: South African adult
      general population. PARTICIPANTS: For metrics of alcohol use by SES, sex and age:
      27 070 adults that participated in a nationally representative survey in 2012.
      For HRs of dying from HIV/AIDS by SES: 87 029 adults that participated in a
      cohort study (years 2000 to 2014) based out of the Umkhanyakude district, KwaZulu
      Natal. MAIN OUTCOME MEASURES: Alcohol-attributable fractions for HIV/AIDS
      mortality by SES, age and sex were calculated based on the risk of engaging in
      condom-unprotected sex under the influence of alcohol and interactions between
      SES and alcohol use. Age-standardised HIV/AIDS mortality rates attributable to
      alcohol by SES and sex were estimated using alcohol-attributable fractions and
      SES-specific and sex-specific death counts. Rate ratios were calculated comparing
      age-standardised rates in low versus high SES by sex. RESULTS: The age
      standardised HIV/AIDS mortality rate attributable to alcohol was 31.0 (95%
      uncertainty interval (UI) 21.6 to 41.3) and 229.6 (95% UI 108.8 to 351.6) deaths
      per 100 000 adults for men of high and low SES, respectively. For women the
      respective rates were 10.8 (95% UI 5.5 to 16.1) and 75.5 (95% UI 31.2 to 144.9).
      The rate ratio was 7.4 (95% UI 3.4 to 13.2) for men and 7.0 (95% UI 2.8 to 18.2)
      for women. Sensitivity analyses corroborated marked differences in alcohol
      attributable HIV/AIDS mortality, with rate ratios between 2.7 (95% UI 0.8 to 7.6;
      women) and 15.1 (95% UI 6.8 to 27.7; men). CONCLUSIONS: The present study showed
      that alcohol use contributed considerably to the socioeconomic differences in
      HIV/AIDS mortality. Targeting HIV infection under the influence of alcohol is a
      promising strategy for interventions to reduce the HIV/AIDS burden and related
      socioeconomic differences in South Africa.

PMID- 29467132
TI  - Rapid diagnostic test for antenatal syphilis screening in low-income and middle
      income countries: a systematic review and meta-analysis.
AB  - OBJECTIVES: To undertake a systematic review and meta-analysis to evaluate the
      test performance including sensitivity and specificity of rapid
      immunochromatographic syphilis (ICS) point-of-care (POC) tests at antenatal
      clinics compared with reference standard tests (non-treponemal (TP) and TP tests)
      for active syphilis in pregnant women. METHODS: Five electronic databases were
      searched (PubMed, EMBASE, CRD, Cochrane Library and LILACS) to March 2016 for
      diagnostic accuracy studies of ICS test and standard reference tests for syphilis
      in pregnant women. Methodological quality was assessed using QUADAS-2 (Quality
      Assessment of Diagnostic Accuracy Studies). A bivariate meta-analysis was
      undertaken to generate pooled estimates of diagnostic parameters. Results were
      presented using a coupled forest plot of sensitivity and specificity and a
      scatter plot. RESULTS: The methodological quality of the five included studies
      with regards to risk of bias and applicability concern judgements was either low
      or unclear. One study was judged as high risk of bias for patient selection due
      to exclusion of pregnant women with a previous history of syphilis, and one study
      was judged at high risk of bias for study flow and timing as not all patients
      were included in the analysis. Five studies contributed to the meta-analysis,
      providing a pooled sensitivity and specificity for ICS of 0.85 (95% CrI: 0.73 to
      0.92) and 0.98 (95% CrI: 0.95 to 0.99), respectively. CONCLUSIONS: This review
      and meta-analysis observed that rapid ICS POC tests have a high sensitivity and
      specificity when performed in pregnant women at antenatal clinics. However, the
      methodological quality of the existing evidence base should be taken into
      consideration when interpreting these results. PROSPERO REGISTRATION NUMBER:
      CRD42016036335.

PMID- 29467133
TI  - Time-dependent risks of cancer clustering among couples: a nationwide population
      based cohort study in Taiwan.
AB  - OBJECTIVES: Spousal clustering of cancer warrants attention. Whether the common
      environment or high-age vulnerability determines cancer clustering is unclear.
      The risk of clustering in couples versus non-couples is undetermined. The time to
      cancer clustering after the first cancer diagnosis is yet to be reported. This
      study investigated cancer clustering over time among couples by using nationwide
      data. METHODS: A cohort of 5643 married couples in the 2002-2013 Taiwan National
      Health Insurance Research Database was identified and randomly matched with 5643
      non-couple pairs through dual propensity score matching. Factors associated with
      clustering (both spouses with tumours) were analysed by using the Cox
      proportional hazard model. RESULTS: Propensity-matched analysis revealed that the
      risk of clustering of all tumours among couples (13.70%) was significantly higher
      than that among non-couples (11.84%) (OR=1.182, 95% CI 1.058 to 1.321, P=0.0031).
      The median time to clustering of all tumours and of malignant tumours was 2.92
      and 2.32 years, respectively. Risk characteristics associated with clustering
      included high age and comorbidity. CONCLUSIONS: Shared environmental factors
      among spouses might be linked to a high incidence of cancer clustering. Cancer
      incidence in one spouse may signal cancer vulnerability in the other spouse.
      Promoting family-oriented cancer care in vulnerable families and preventing
      shared lifestyle risk factors for cancer are suggested.

PMID- 29467134
TI  - NHS Diabetes Prevention Programme in England: formative evaluation of the
      programme in early phase implementation.
AB  - OBJECTIVES: Evaluation of the demonstrator phase and first wave roll-out of the
      National Health Service (NHS) Diabetes Prevention Programme (DPP) in England. To
      examine: (1) intervention design, provision and fidelity assessment procedures;
      (2) risk assessment and recruitment pathways and (3) data collection for
      monitoring and evaluation. To provide recommendations informing decision makers
      on programme quality, improvements and future evaluation. DESIGN: We reviewed
      programme documents, mapping against the NHS DPP specification and National
      Institute for Health and Care Excellence (NICE) public health guideline: Type 2
      diabetes (T2D) prevention in people at high risk (PH38), conducted qualitative
      research using individual interviews and focus group discussions with
      stakeholders and examined recruitment, fidelity and data collection procedures.
      SETTING: Seven NHS DPP demonstrator sites and, subsequently, 27 first wave areas
      across England. INTERVENTIONS: Intensive behavioural intervention with weight
      loss, diet and physical activity goals. The national programme specifies at least
      13 sessions over 9 months, delivered face to face to groups of 15-20 adults with
      non-diabetic hyperglycaemia, mainly recruited from primary care and NHS Health
      Checks. PARTICIPANTS: Participants for qualitative research were purposively
      sampled to provide a spread of stakeholder experience. Documents for review were
      provided via the NHS DPP Management Group. FINDINGS: The NHS DPP specification
      reflected current evidence with a clear framework for service provision.
      Providers, with national capacity to deliver, supplied intervention plans
      compliant with this framework. Stakeholders highlighted limitations in fidelity
      assessment and recruitment and retention challenges, especially in reach and
      equity, that could adversely impact on implementation. Risk assessment for first
      wave eligibility differed from NICE guidance. CONCLUSIONS: The NHS DPP provides
      an evidence-based behavioural intervention for prevention of T2D in adults at
      high risk, with capacity to deliver nationally. Framework specification allows
      for balance between consistency and contextual variation in intervention
      delivery, with session details devolved to providers. Limitations in fidelity
      assurance, data collection procedures and recruitment issues could adversely
      impact on intervention effectiveness and restrict evaluation.

PMID- 29467135
TI  - Physiological responses to arm versus leg activity in patients with chronic
      obstructive pulmonary disease: a systematic review protocol.
AB  - INTRODUCTION: Compared with healthy older adults, people with chronic obstructive
      pulmonary disease (COPD) have reduced capacity and increased symptoms during leg
      and arm activities. While the mechanisms underlying limitations and symptoms
      during leg activities have been investigated in detail, limitations and symptoms
      during arm activities are not well understood, and the potential differences
      between physiological responses of leg and arm activities have not been
      systematically synthesised. Determining physiological responses and symptoms of
      arm activities compared with physiological responses and symptoms of leg
      activities will help us understand the mechanisms behind the difficulties that
      people with COPD experience when performing physical activities, and determine
      how exercise training should be prescribed. Thus, the aim of this systematic
      review is to compare the physiological responses and symptoms during activities
      involving the arms relative to activities involving the legs in people diagnosed
      with COPD. METHODS AND ANALYSES: This protocol is reported in line with the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols.
      Potentially relevant studies will be identified from CINAHL, EMBASE, PEDro,
      Cochrane Central Register of Controlled Trials and PubMed databases. The
      Population, Exposure, Comparator, Outcomes, and Study characteristics framework
      will be used to systematise the process of selecting and extracting data from
      relevant studies. Assessment of the methodological quality of the studies will be
      done by using the 14 most relevant components from the checklist by Downs and
      Black. The result will be presented with a narrative synthesis, and if
      appropriate with meta-analyses. ETHICS AND DISSEMINATION: Ethical approval is not
      required as this study is a systematic review. It is our intention to submit the
      results of our review for peer-reviewed publication. PROSPERO REGISTRATION
      NUMBER: CRD42017074476.

PMID- 29467137
TI  - Health state utility values among children and adolescents with disabilities:
      protocol for a systematic review.
AB  - INTRODUCTION: Increasingly, assessment of healthcare technologies and
      interventions requires the assessment of both costs and utilities. Health state
      utility values (HSUVs) are measured using a range of generic and condition
      specific measures. While reviews have identified that generic measures of HSUVs
      may lack validity in adults with conditions that result in physical disability,
      there is little information available on the methods used to obtain HSUVs in
      children and adolescents with disabilities. The objectives of this systematic
      review are to describe the methods used to obtain HSUVs, including mode of
      administration and psychometric properties, and provide summary statistics for
      HSUVs among children and adolescents with disabilities. METHODS AND ANALYSIS: The
      following databases will be searched from inception for English-language studies
      of any design: PubMed, PsychInfo, Medline, Scopus, CINAHL Plus, Econlit and
      EMBASE databases. Two reviewers will independently screen titles, abstracts and
      full text articles for studies reporting HSUVs and/or data on the psychometric
      properties of preference-based measures for children and adolescents with
      disabilities aged up to 19 years. Two reviewers will independently extract data
      items including descriptors of the study methods and sample, instruments used to
      capture HSUVs, summary statistics for HSUVs and items relating to the quality of
      reporting. A descriptive summary of results from included studies and summary
      statistics for HSUVs will be presented. If sufficient data is identified, we will
      pool summary statistics for HSUVs according to the method used to obtain the HSUV
      using a random effects model. In addition, we will explore the determinants of
      the HSUVs using a meta-regression. ETHICS AND DISSEMINATION: Ethical approval
      will not be required as no original data will be collected as part of this
      review. The completed review will be submitted for publication in a peer-reviewed
      journal and presentation at conferences. PROSPERO REGISTRATION NUMBER:
      CRD42018086574.

PMID- 29467136
TI  - Attitudes and perceptions of health professionals towards management of
      hypothyroidism in general practice: a qualitative interview study.
AB  - OBJECTIVE: To explore the attitudes and perceptions of health professionals
      towards management of hypothyroidism that contributes to the suboptimal treatment
      of hypothyroidism in general practice. DESIGN: A qualitative interview study
      using semistructured interviews. PARTICIPANTS: Sixteen participants were
      interviewed between March and August 2016 comprising nine general practitioners
      (GPs), four pharmacists, two practice nurses and one nurse practitioner. SETTING:
      General practice and community pharmacies in the counties of Northumberland, Tyne
      and Wear, Stockton-on-Tees and North Cumbria, North of England, UK. METHOD: A
      grounded-theory approach was used to generate themes from interviews, which were
      underpinned by the theory of planned behaviour to give explanation to the data.
      RESULTS: Although health professionals felt that hypothyroidism was easy to
      manage, GPs and nurses generally revealed inadequate knowledge of medication
      interactions and levothyroxine pharmacokinetics. Pharmacists felt limited in the
      advice that they provide to patients due to lack of access to patient records.
      Most GPs and nurses followed local guidelines, and relied on blood tests over
      clinical symptoms to adjust levothyroxine dose. The information exchanged between
      professional and patient was usually restricted by time and often centred on
      symptoms rather than patient education. Health professionals felt that incorrect
      levothyroxine adherence was the main reason behind suboptimal treatment, although
      other factors such as comorbidity and concomitant medication were mentioned.
      Enablers perceived by health professionals to improve the management of
      hypothyroidism included continuity of care, blood test reminders, system alerts
      for interfering medications and prescription renewal, and accessible blood tests
      and levothyroxine prescriptions for patients. CONCLUSION: There is a significant
      health professional behavioural component to the management of hypothyroidism.
      Addressing the differences in patient and professional knowledge and perceptions
      could reduce the barriers to optimal treatment, while continuity of care and
      increased involvement of pharmacists and practice nurses would help to promote
      optimal thyroid replacement.

PMID- 29467139
TI  - SULFATION PATHWAYS: Formation and hydrolysis of sulfonated estrogens in the
      porcine testis and epididymis.
AB  - Boars exhibit high concentrations of sulfonated estrogens (SE) mainly originating
      from the testicular-epididymal compartment. Intriguingly, in porcine Leydig
      cells, sulfonation of estrogens is colocalized with aromatase and steroid
      sulfatase (STS), indicating that de novo synthesis of unconjugated estrogens
      (UE), their sulfonation and hydrolysis of SE occur within the same cell type. So
      far in boars no plausible concept concerning the role of SE has been put forward.
      To obtain new information on SE formation and hydrolysis, the porcine testicular
      epididymal compartment was screened for the expression of the estrogen-specific
      sulfotransferase SULT1E1 and STS applying real-time RT-qPCR, Western blot and
      immunohistochemistry. The epididymal head was identified as the major site of
      SULT1E1 expression, whereas in the testis, it was virtually undetectable.
      However, SE tissue concentrations are clearly consistent with the testis as the
      predominant site of estrogen sulfonation. Results from measurements of estrogen
      sulfotransferase activity indicate that in the epididymis, SULT1E1 is the
      relevant enzyme, whereas in the testis, estrogens are sulfonated by a different
      sulfotransferase with a considerably lower affinity. STS expression and activity
      was high in the testis (Leydig cells, rete testis epithelium) but also present
      throughout the epididymis. In the epididymis, SULT1E1 and STS were colocalized in
      the ductal epithelium, and there was evidence for their apocrine secretion into
      the ductal lumen. The results suggest that in porcine Leydig cells, SE may be
      produced as a reservoir to support the levels of bioactive UE via the sulfatase
      pathway during periods of low activity of the pulsatile testicular
      steroidogenesis.

PMID- 29467140
TI  - Central regulation of food intake in fish: an evolutionary perspective.
AB  - Evidence indicates that central regulation of food intake is well conserved along
      the vertebrate lineage, at least between teleost fish and mammals. However,
      several differences arise in the comparison between both groups. In this review,
      we describe similarities and differences between teleost fish and mammals on an
      evolutionary perspective. We focussed on the existing knowledge of specific fish
      features conditioning food intake, anatomical homologies and analogies between
      both groups as well as the main signalling pathways of neuroendocrine and
      metabolic nature involved in the homeostatic and hedonic central regulation of
      food intake.

PMID- 29467138
TI  - Pathways: patient-centred decision counselling for women at risk of cancer
      related infertility: a protocol for a comparative effectiveness cluster
      randomised trial.
AB  - INTRODUCTION: National guidelines recommend that all reproductive-age women with
      cancer be informed of their fertility risks and offered referral to fertility
      specialists to discuss fertility preservation options. However, reports indicate
      that only 5% of patients have consultations, and rates of long-term infertility
      related distress remain high. Previous studies report several barriers to
      fertility preservation; however, initial success has been reported using provider
      education, patient decision aids and navigation support. This protocol will test
      effects of a multicomponent intervention compared with usual care on women's
      fertility preservation knowledge and decision-making outcomes. METHODS AND
      ANALYSIS: This cluster-randomised trial will compare the multicomponent
      intervention (provider education, patient decision aid and navigation support)
      with usual care (consultation and referral, if requested). One hundred newly
      diagnosed English-speaking women of reproductive age who are at risk of cancer
      related infertility will be recruited from four regional oncology clinics.The
      Pathways patient decision aid website provides (1) up-to-date evidence and
      descriptions of fertility preservation and other family-building options,
      tailored to cancer type; (2) structured guidance to support personalising the
      information and informed decision-making; and (3) a printable summary to help
      women prepare for discussions with their oncologist and/or fertility specialist.
      Four sites will be randomly assigned to intervention or control groups.
      Participants will be recruited after their oncology consultation and asked to
      complete online questionnaires at baseline, 1 week and 2 months to assess their
      demographics, fertility preservation knowledge, and decision-making process and
      quality. The primary outcome (decisional conflict) will be tested using Fisher's
      exact test. Secondary outcomes will be assessed using generalised linear mixed
      models, and sensitivity analyses will be conducted, as appropriate. ETHICS AND
      DISSEMINATION: The University of Texas MD Anderson Cancer Center provided
      approval and ongoing review of this protocol. Results will be presented at
      relevant scientific meetings and submitted for publication in a peer-reviewed
      journal. TRIAL REGISTRATION NUMBER: NCT03141437; Pre-results.

PMID- 29467141
TI  - The role of Sirtuin1-PPARgamma axis in placental development and function.
AB  - Placental development is important for proper in utero growth and development of
      the fetus, as well as maternal well-being during pregnancy. Abnormal
      differentiation of placental epithelial cells, called trophoblast, is at the root
      of multiple pregnancy complications, including miscarriage, the maternal
      hypertensive disorder preeclampsia and intrauterine growth restriction. The
      ligand-activated nuclear receptor, PPARgamma, and nutrient sensor, Sirtuin-1,
      both play a role in numerous pathways important to cell survival and
      differentiation, metabolism and inflammation. However, each has also been
      identified as a key player in trophoblast differentiation and placental
      development. This review details these studies, and also describes how various
      stressors, including hypoxia and inflammation, alter the expression or activity
      of PPARgamma and Sirtuin-1, thereby contributing to placenta-based pregnancy
      complications.

PMID- 29467142
TI  - The Authors Reply.

PMID- 29467143
TI  - Antibodies Can Extenuate Polyomavirus Infections.

PMID- 29467144
TI  - Correction: A Fusion Protein Encoding the Second Extracellular Domain of CCR5
      Arrests Chemokine-Induced Cosignaling and Effectively Suppresses Ongoing
      Experimental Autoimmune Encephalomyelitis.

PMID- 29467146
TI  - The Development of Neuronal Polarity: A Retrospective View.
AB  - In 1988, Carlos Dotti, Chris Sullivan, and I published a paper on the
      establishment of polarity by hippocampal neurons in culture, which continues to
      be frequently cited 30 years later (Dotti et al., 1988). By following individual
      neurons from the time of plating until they had formed well developed axonal and
      dendritic arbors, we identified the five stages of development that lead to the
      mature expression of neuronal polarity. We were surprised to find that, before
      axon formation, the cells pass through a multipolar phase, in which several,
      apparently identical short neurites undergo periods of extension and retraction.
      Then one of these neurites begins a period of prolonged growth, becoming the
      definitive axon; the remaining neurites subsequently become dendrites. This
      observation suggested that any of the initial neurites were capable of becoming
      axons, a hypothesis confirmed by later work. In this Progressions article, I will
      try to recall the circumstances that led to this work, recapture some of the
      challenges we faced in conducting these experiments, and consider why some of
      today's neuroscientists still find this paper relevant.

PMID- 29467147
TI  - Alectinib for advanced ALK-positive non-small-cell lung cancer.
AB  - PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety and
      tolerability, dosage and administration, and place in therapy of alectinib for
      treatment of patients with non-small-cell lung cancer (NSCLC) are reviewed.
      SUMMARY: In patients with NSCLC driven by mutations of ALK, the gene coding for
      anaplastic lymphoma kinase (ALK), treatment with the ALK inhibitor crizotinib has
      been found to provide median progression-free survival (PFS) of 10.9 months;
      however, therapeutic failures and tumor progression to brain metastases are
      common with crizotinib use, prompting research to find more potent and tolerable
      ALK inhibitors that target major oncogenic drivers of NSCLC. Alectinib is a next
      generation ALK inhibitor initially approved by the Food and Drug Administration
      for use in patients with metastatic ALK-positive NSCLC who are intolerant of or
      have disease progression during crizotinib therapy. In clinical trials, alectinib
      was found effective for delaying disease progression and, more importantly,
      reducing brain metastases in patients with NSCLC who developed resistance or
      intolerance to previous crizotinib therapy. Published data from clinical trials
      indicate that the most common grade 1 and 2 adverse effects associated with
      alectinib use are fatigue, constipation, peripheral edema, and myalgia; the most
      common grade 3 or 4 reactions include increases in creatine phosphokinase,
      alanine aminotransferase, and aspartate aminotransferase levels. CONCLUSION:
      Alectinib appears to be effective and safe for use in patients with metastatic
      ALK-positive NSCLC, with demonstrated superiority over crizotinib in terms of PFS
      rates. Research to better define ALK inhibitor resistance mechanisms and
      alectinib's place in therapy is ongoing.

PMID- 29467145
TI  - Electrophysiological Signatures of Spatial Boundaries in the Human Subiculum.
AB  - Environmental boundaries play a crucial role in spatial navigation and memory
      across a wide range of distantly related species. In rodents, boundary
      representations have been identified at the single-cell level in the subiculum
      and entorhinal cortex of the hippocampal formation. Although studies of
      hippocampal function and spatial behavior suggest that similar representations
      might exist in humans, boundary-related neural activity has not been identified
      electrophysiologically in humans until now. To address this gap in the
      literature, we analyzed intracranial recordings from the hippocampal formation of
      surgical epilepsy patients (of both sexes) while they performed a virtual spatial
      navigation task and compared the power in three frequency bands (1-4, 4-10, and
      30-90 Hz) for target locations near and far from the environmental boundaries.
      Our results suggest that encoding locations near boundaries elicited stronger
      theta oscillations than for target locations near the center of the environment
      and that this difference cannot be explained by variables such as trial length,
      speed, movement, or performance. These findings provide direct evidence of
      boundary-dependent neural activity localized in humans to the subiculum, the
      homolog of the hippocampal subregion in which most boundary cells are found in
      rodents, and indicate that this system can represent attended locations that
      rather than the position of one's own body.SIGNIFICANCE STATEMENT Spatial
      computations using environmental boundaries are an integral part of the brain's
      spatial mapping system. In rodents, border/boundary cells in the subiculum and
      entorhinal cortex reveal boundary coding at the single-neuron level. Although
      there is good reason to believe that such representations also exist in humans,
      the evidence has thus far been limited to functional neuroimaging studies that
      broadly implicate the hippocampus in boundary-based navigation. By combining
      intracranial recordings with high-resolution imaging of hippocampal subregions,
      we identified a neural marker of boundary representation in the human subiculum.

PMID- 29467148
TI  - Controlling postoperative use of i.v. acetaminophen at an academic medical
      center.
AB  - PURPOSE: Results of an interprofessional formulary initiative to decrease
      postoperative prescribing of i.v. acetaminophen are reported. SUMMARY: After a
      medical center added i.v. acetaminophen to its formulary, increased prescribing
      of the i.v. formulation and a 3-fold price increase resulted in monthly spending
      of more than $40,000, prompting an organizationwide effort to curtail that cost
      while maintaining effective pain management. The surgery, anesthesia, and
      pharmacy departments applied the Institute for Healthcare Improvement's Model for
      Improvement to implement (1) pharmacist-led enforcement of prescribing
      restrictions, (2) retrospective evaluation of i.v. acetaminophen's impact on
      rates of opioid-related adverse effects, (3) restriction of prescribing of the
      drug to 1 postoperative dose on select patient care services, and (4) guideline
      driven pain management according to an enhanced recovery after surgery (ERAS)
      protocol. Monitored metrics included the monthly i.v. acetaminophen prescribing
      rate, the proportion of i.v. acetaminophen orders requiring pharmacist
      intervention to enforce prescribing restrictions, and prescribing rates for
      select adjunctive analgesics. Within a year of project implementation, the mean
      monthly i.v. acetaminophen prescribing rate decreased by 83% from baseline to
      about 6 doses per 100 patient-days, with a decline in the monthly drug cost to
      about $4,000. Documented pharmacist interventions increased 2.7-fold, and use of
      oral acetaminophen, ketorolac, and gabapentin in ERAS areas increased by 18%
      overall. CONCLUSION: An interprofessional initiative at a large medical center
      reduced postoperative use of i.v. acetaminophen by more than 80% and yielded over
      $400,000 in annual cost savings.

PMID- 29467149
TI  - Zulfiqar Bhutta: A better world for children.

PMID- 29467151
TI  - Junior doctors take trust to court for denying them breaks every four hours.

PMID- 29467152
TI  - David Oliver: Getting serious about prevention.

PMID- 29467150
TI  - High-Sensitivity Troponin I Levels and Coronary Artery Disease Severity,
      Progression, and Long-Term Outcomes.
AB  - BACKGROUND: The associations between high-sensitivity troponin I (hsTnI) levels
      and coronary artery disease (CAD) severity and progression remain unclear. We
      investigated whether there is an association between hsTnI and angiographic
      severity and progression of CAD and whether the predictive value of hsTnI level
      for incident cardiovascular outcomes is independent of CAD severity. METHODS AND
      RESULTS: In 3087 patients (aged 63+/-12 years, 64% men) undergoing cardiac
      catheterization without evidence of acute myocardial infarction, the severity of
      CAD was calculated by the number of major coronary arteries with >=50% stenosis
      and the Gensini score. CAD progression was assessed in a subset of 717 patients
      who had undergone >=2 coronary angiograms >3 months before enrollment. Patients
      were followed up for incident all-cause mortality and incident cardiovascular
      events. Of the total population, 11% had normal angiograms, 23% had
      nonobstructive CAD, 20% had 1-vessel CAD, 20% had 2-vessel CAD, and 26% had 3
      vessel CAD. After adjusting for age, sex, race, body mass index, smoking,
      hypertension, diabetes mellitus history, and renal function, hsTnI levels were
      independently associated with the severity of CAD measured by the Gensini score
      (log 2 beta=0.31; 95% confidence interval, 0.18-0.44; P<0.001) and with CAD
      progression (log 2 beta=0.36; 95% confidence interval, 0.14-0.58; P=0.001). hsTnI
      level was also a significant predictor of incident death, cardiovascular death,
      myocardial infarction, revascularization, and cardiac hospitalizations,
      independent of the aforementioned covariates and CAD severity. CONCLUSIONS:
      Higher hsTnI levels are associated with the underlying burden of coronary
      atherosclerosis, more rapid progression of CAD, and higher risk of all-cause
      mortality and incident cardiovascular events. Whether more aggressive treatment
      aimed at reducing hsTnI levels can modulate disease progression requires further
      investigation.

PMID- 29467153
TI  - Idalopirdine: another disappointment for people with dementia.

PMID- 29467154
TI  - Doctors can withdraw treatment from child on life support, says judge.

PMID- 29467155
TI  - Australian exam "shambles" forces registrars into resits.

PMID- 29467156
TI  - The art of giving life.

PMID- 29467157
TI  - Improving the reporting of tennis injuries: the use of workload data as the
      denominator?

PMID- 29467158
TI  - Neglected or abused children still receive little help, causing problems in
      adulthood.

PMID- 29467160
TI  - Vaccine development might be handled more effectively in biotech companies than
      in academia.

PMID- 29467162
TI  - Septic Arthritis Versus Lyme Arthritis: A Case of Diagnostic Difficulty.

PMID- 29467161
TI  - Outcomes of non-invasive diagnostic modalities for the detection of coronary
      artery disease: network meta-analysis of diagnostic randomised controlled trials.
AB  - OBJECTIVE: To evaluate differences in downstream testing, coronary
      revascularisation, and clinical outcomes following non-invasive diagnostic
      modalities used to detect coronary artery disease. DESIGN: Systematic review and
      network meta-analysis. DATA SOURCES: Medline, Medline in process, Embase,
      Cochrane Library for clinical trials, PubMed, Web of Science, SCOPUS, WHO
      International Clinical Trials Registry Platform, and Clinicaltrials.gov.
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Diagnostic randomised controlled
      trials comparing non-invasive diagnostic modalities in patients presenting with
      symptoms suggestive of low risk acute coronary syndrome or stable coronary artery
      disease. DATA SYNTHESIS: A random effects network meta-analysis synthesised
      available evidence from trials evaluating the effect of non-invasive diagnostic
      modalities on downstream testing and patient oriented outcomes in patients with
      suspected coronary artery disease. Modalities included exercise
      electrocardiograms, stress echocardiography, single photon emission computed
      tomography-myocardial perfusion imaging, real time myocardial contrast
      echocardiography, coronary computed tomographic angiography, and cardiovascular
      magnetic resonance. Unpublished outcome data were obtained from 11 trials.
      RESULTS: 18 trials of patients with low risk acute coronary syndrome (n=11 329)
      and 12 trials of those with suspected stable coronary artery disease (n=22 062)
      were included. Among patients with low risk acute coronary syndrome, stress
      echocardiography, cardiovascular magnetic resonance, and exercise
      electrocardiograms resulted in fewer invasive referrals for coronary angiography
      than coronary computed tomographic angiography (odds ratio 0.28 (95% confidence
      interval 0.14 to 0.57), 0.32 (0.15 to 0.71), and 0.53 (0.28 to 1.00),
      respectively). There was no effect on the subsequent risk of myocardial
      infarction, but estimates were imprecise. Heterogeneity and inconsistency were
      low. In patients with suspected stable coronary artery disease, an initial
      diagnostic strategy of stress echocardiography or single photon emission computed
      tomography-myocardial perfusion imaging resulted in fewer downstream tests than
      coronary computed tomographic angiography (0.24 (0.08 to 0.74) and 0.57 (0.37 to
      0.87), respectively). However, exercise electrocardiograms yielded the highest
      downstream testing rate. Estimates for death and myocardial infarction were
      imprecise without clear discrimination between strategies. CONCLUSIONS: For
      patients with low risk acute coronary syndrome, an initial diagnostic strategy of
      stress echocardiography or cardiovascular magnetic resonance is associated with
      fewer referrals for invasive coronary angiography and revascularisation
      procedures than non-invasive anatomical testing, without apparent impact on the
      future risk of myocardial infarction. For suspected stable coronary artery
      disease, there was no clear discrimination between diagnostic strategies
      regarding the subsequent need for invasive coronary angiography, and differences
      in the risk of myocardial infarction cannot be ruled out. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO registry no CRD42016049442.

PMID- 29467163
TI  - Stac proteins associate with the critical domain for excitation-contraction
      coupling in the II-III loop of CaV1.1.
AB  - In skeletal muscle, residues 720-764/5 within the CaV1.1 II-III loop form a
      critical domain that plays an essential role in transmitting the excitation
      contraction (EC) coupling Ca2+ release signal to the type 1 ryanodine receptor
      (RyR1) in the sarcoplasmic reticulum. However, the identities of proteins that
      interact with the loop and its critical domain and the mechanism by which the II
      III loop regulates RyR1 gating remain unknown. Recent work has shown that EC
      coupling in skeletal muscle of fish and mice depends on the presence of Stac3, an
      adaptor protein that is highly expressed only in skeletal muscle. Here, by using
      colocalization as an indicator of molecular interactions, we show that Stac3, as
      well as Stac1 and Stac2 (predominantly neuronal Stac isoforms), interact with the
      II-III loop of CaV1.1. Further, we find that these Stac proteins promote the
      functional expression of CaV1.1 in tsA201 cells and support EC coupling in Stac3
      null myotubes and that Stac3 is the most effective. Coexpression in tsA201 cells
      reveals that Stac3 interacts only with II-III loop constructs containing the
      majority of the CaV1.1 critical domain residues. By coexpressing Stac3 in
      dysgenic (CaV1.1-null) myotubes together with CaV1 constructs whose chimeric II
      III loops had previously been tested for functionality, we reveal that the
      ability of Stac3 to interact with them parallels the ability of these constructs
      to mediate skeletal type EC coupling. Based on coexpression in tsA201 cells, the
      interaction of Stac3 with the II-III loop critical domain does not require the
      presence of the PKC C1 domain in Stac3, but it does require the first of the two
      SH3 domains. Collectively, our results indicate that activation of RyR1 Ca2+
      release by CaV1.1 depends on Stac3 being bound to critical domain residues in the
      II-III loop.

PMID- 29467164
TI  - The discovery of the ability of rod photoreceptors to signal single photons.
AB  - Vertebrate rod photoreceptors evolved the astonishing ability to respond reliably
      to single photons. In parallel, the proximate neurons of the visual system
      evolved the ability to reliably encode information from a few single-photon
      responses (SPRs) as arising from the presence of an object of interest in the
      visual environment. These amazing capabilities were first inferred from
      measurements of human visual threshold by Hecht et al. (1942), whose paper has
      since been cited over 1,000 times. Subsequent research, in part inspired by Hecht
      et al.'s discovery, has directly measured rod SPRs, characterized the molecular
      mechanism responsible for their generation, and uncovered much about the
      specializations in the retina that enable the reliable transmission of SPRs in
      the teeth of intrinsic neuronal noise.

PMID- 29467165
TI  - Improving the characterization of calcium channel gating pore currents with
      Stac3.

PMID- 29467166
TI  - Polarised epithelial monolayers of the gastric mucosa reveal insights into
      mucosal homeostasis and defence against infection.
AB  - OBJECTIVE: Helicobacter pylori causes life-long colonisation of the gastric
      mucosa, leading to chronic inflammation with increased risk of gastric cancer.
      Research on the pathogenesis of this infection would strongly benefit from an
      authentic human in vitro model. DESIGN: Antrum-derived gastric glands from
      surgery specimens served to establish polarised epithelial monolayers via a
      transient air-liquid interface culture stage to study cross-talk with H. pylori
      and the adjacent stroma. RESULTS: The resulting 'mucosoid cultures', so named
      because they recapitulate key characteristics of the gastric mucosa, represent
      normal stem cell-driven cultures that can be passaged for months. These highly
      polarised columnar epithelial layers encompass the various gastric antral cell
      types and secrete mucus at the apical surface. By default, they differentiate
      towards a foveolar, MUC5AC-producing phenotype, whereas Wnt signalling stimulates
      proliferation of MUC6-producing cells and preserves stemness-reminiscent of the
      gland base. Stromal cells from the lamina propria secrete Wnt inhibitors,
      antagonising stem-cell niche signalling and inducing differentiation. On
      infection with H. pylori, a strong inflammatory response is induced
      preferentially in the undifferentiated basal cell phenotype. Infection of
      cultures for several weeks produces foci of viable bacteria and a persistent
      inflammatory condition, while the secreted mucus establishes a barrier that only
      few bacteria manage to overcome. CONCLUSION: Gastric mucosoid cultures faithfully
      reproduce the features of normal human gastric epithelium, enabling new
      approaches for investigating the interaction of H. pylori with the epithelial
      surface and the cross-talk with the basolateral stromal compartment. Our
      observations provide striking insights in the regulatory circuits of inflammation
      and defence.

PMID- 29467167
TI  - Can Family Planning Service Statistics Be Used to Track Population-Level
      Outcomes?
AB  - The need for annual family planning program tracking data under the Family
      Planning 2020 (FP2020) initiative has contributed to renewed interest in family
      planning service statistics as a potential data source for annual estimates of
      the modern contraceptive prevalence rate (mCPR). We sought to assess (1) how well
      a set of commonly recorded data elements in routine service statistics systems
      could, with some fairly simple adjustments, track key population-level outcome
      indicators, and (2) whether some data elements performed better than others. We
      used data from 22 countries in Africa and Asia to analyze 3 data elements
      collected from service statistics: (1) number of contraceptive commodities
      distributed to clients, (2) number of family planning service visits, and (3)
      number of current contraceptive users. Data quality was assessed via analysis of
      mean square errors, using the United Nations Population Division World
      Contraceptive Use annual mCPR estimates as the "gold standard." We also examined
      the magnitude of several components of measurement error: (1) variance, (2) level
      bias, and (3) slope (or trend) bias. Our results indicate modest levels of
      tracking error for data on commodities to clients (7%) and service visits (10%),
      and somewhat higher error rates for data on current users (19%). Variance and
      slope bias were relatively small for all data elements. Level bias was by far the
      largest contributor to tracking error. Paired comparisons of data elements in
      countries that collected at least 2 of the 3 data elements indicated a modest
      advantage of data on commodities to clients. None of the data elements considered
      was sufficiently accurate to be used to produce reliable stand-alone annual
      estimates of mCPR. However, the relatively low levels of variance and slope bias
      indicate that trends calculated from these 3 data elements can be productively
      used in conjunction with the Family Planning Estimation Tool (FPET) currently
      used to produce annual mCPR tracking estimates for FP2020.

PMID- 29467168
TI  - Whole-Genome Analysis Illustrates Global Clonal Population Structure of the
      Ubiquitous Dermatophyte Pathogen Trichophyton rubrum.
AB  - Dermatophytes include fungal species that infect humans, as well as those that
      also infect other animals or only grow in the environment. The dermatophyte
      species Trichophyton rubrum is a frequent cause of skin infection in
      immunocompetent individuals. While members of the T. rubrum species complex have
      been further categorized based on various morphologies, their population
      structure and ability to undergo sexual reproduction are not well understood. In
      this study, we analyze a large set of T. rubrum and T. interdigitale isolates to
      examine mating types, evidence of mating, and genetic variation. We find that
      nearly all isolates of T. rubrum are of a single mating type, and that incubation
      with T. rubrum "morphotype" megninii isolates of the other mating type failed to
      induce sexual development. While the region around the mating type locus is
      characterized by a higher frequency of SNPs compared to other genomic regions, we
      find that the population is remarkably clonal, with highly conserved gene
      content, low levels of variation, and little evidence of recombination. These
      results support a model of recent transition to asexual growth when this species
      specialized to growth on human hosts.

PMID- 29467169
TI  - Functional Redundancy of DICER Cofactors TARBP2 and PRKRA During Murine
      Embryogenesis Does Not Involve miRNA Biogenesis.
AB  - Several in vitro studies have suggested that canonical microRNA (miRNA)
      biogenesis requires the DICER cofactors TARBP2 and PRKRA for processing of pre
      miRNAs to mature miRNAs. To investigate the roles of TARBP2 and PRKRA in miRNA
      biogenesis in vivo, and to determine possible functional redundancy, we first
      compared the phenotypes of Tarbp2 and Prkra single and double mutants. In
      contrast to Dicer -/- embryos, which die by embryonic day 7.5 (E7.5), single
      Tarbp2 -/- and Prkra -/- mice survive beyond E7.5 and either die perinatally or
      survive and exhibit cranial/facial abnormalities, respectively. In contrast, only
      a few Tarbp2 -/- ; Prkra -/- double mutants survived beyond E12.5, suggesting
      genetic redundancy between Tarbp2 and Prkra during embryonic development.
      Sequencing of miRNAs from single-mutant embryos at E15.5 revealed changes in
      abundance and isomiR type in Tarbp2 -/- , but not Prkra -/- , embryos,
      demonstrating that TARBP2, but not PRKRA, functions in miRNA biogenesis of a
      subclass of miRNAs, and suggesting that functional redundancy between TARBP2 and
      PRKRA does not involve miRNA biogenesis.

PMID- 29467171
TI  - Atrialized right ventricular myxoma in a patient with Ebstein's anomaly.
AB  - Ebstein's anomaly is a rare entity affecting around 1 in 200,000 live births and
      accounts for less than 1% of congenital heart diseases. Ebstein's anomaly with an
      associated right-sided myxoma is extremely rare, with only one other case report
      found in the literature. Previous reports have also noted cases of Ebstein's
      anomaly associated with left-sided myxomas. We describe a female patient with, to
      our knowledge, the first case of a histopathologically confirmed right
      ventricular myxoma in the setting of Ebstein's anomaly.

PMID- 29467170
TI  - Rethinking the National Diabetes Prevention Program for Low-Income Whites.

PMID- 29467172
TI  - Amylin Selectively Signals Onto POMC Neurons in the Arcuate Nucleus of the
      Hypothalamus.
AB  - Amylin phosphorylates ERK (p-ERK) in the area postrema to reduce eating and
      synergizes with leptin to phosphorylate STAT3 in the arcuate (ARC) and
      ventromedial (VMN) hypothalamic nuclei to reduce food intake and body weight. The
      current studies assessed potential amylin and amylin-leptin ARC/VMN interactions
      on ERK signaling and their roles in postnatal hypothalamic pathway development.
      In amylin knockout mice, the density of agouti-related protein (AgRP)
      immunoreactive (IR) fibers in the hypothalamic paraventricular nucleus (PVN) was
      increased, while the density of alpha-melanocyte-stimulating hormone (alphaMSH)
      fibers was decreased. In mice deficient of the amylin receptor components
      RAMP1/3, both AgRP and alphaMSH-IR fiber densities were decreased, while only
      alphaMSH-IR fiber density was decreased in rats injected neonatally in the
      ARC/VMN with an adeno-associated virus short hairpin RNA against the amylin core
      receptor. Amylin induced p-ERK in ARC neurons, 60% of which was present in POMC
      expressing neurons, with none in NPY neurons. An amylin-leptin interaction was
      shown by an additive effect on ARC ERK signaling in neonatal rats and a 44%
      decrease in amylin-induced p-ERK in the ARC of leptin receptor-deficient and of
      ob/ob mice. Together, these results suggest that amylin directly acts, through a
      p-ERK-mediated process, on POMC neurons to enhance ARC-PVN alphaMSH pathway
      development.

PMID- 29467173
TI  - qSOFA, SIRS and NEWS for predicting inhospital mortality and ICU admission in
      emergency admissions treated as sepsis.
AB  - BACKGROUND: The third international consensus definition for sepsis recommended
      use of a new prognostic tool, the quick Sequential Organ Failure Assessment
      (qSOFA), based on its ability to predict inhospital mortality and prolonged
      intensive care unit (ICU) stay in patients with suspected infection. While
      several studies have compared the prognostic accuracy of qSOFA to the Systemic
      Inflammatory Response Syndrome (SIRS) criteria in suspected sepsis, few have
      compared qSOFA and SIRS to the widely used National Early Warning Score (NEWS).
      METHODS: This was a retrospective cohort study carried out in a UK tertiary
      centre. The study population comprised emergency admissions in whom sepsis was
      suspected and treated. The accuracy for predicting inhospital mortality and ICU
      admission was calculated and compared for qSOFA, SIRS and NEWS. RESULTS: Among
      1818 patients, 53 were admitted to ICU (3%) and 265 died in hospital (15%). For
      predicting inhospital mortality, the area under the receiver operating
      characteristics curve for NEWS (0.65, 95% CI 0.61 to 0.68) was similar to qSOFA
      (0.62, 95% CI 0.59 to 0.66) (test for difference, P=0.18) and superior to SIRS
      (P<0.001), which was not predictive. The sensitivity of NEWS>=5 (74%, 95% CI 68%
      to 79%) was similar to SIRS>=2 (80%, 95% CI 74% to 84%) and higher than qSOFA>=2
      (37%, 95% CI 31% to 43%). The specificity of NEWS>=5 (43%, 95% CI 41% to 46%) was
      higher than SIRS>=2 (21%, 95% CI 19% to 23%) and lower than qSOFA>=2 (79%, 95% CI
      77% to 81%). The negative predictive value was 88% (86%-90%) for qSOFA, 86% (82%
      89%) for SIRS and 91% (88%-93%) for NEWS. Results were similar for the secondary
      outcome of ICU admission. CONCLUSION: NEWS has equivalent or superior value for
      most test characteristics relative to SIRS and qSOFA, calling into question the
      rationale of adopting qSOFA in institutions where NEWS is already in use.

PMID- 29467175
TI  - Growth affects dispersal success in social mole-rats, but not the duration of
      philopatry.
AB  - In naked mole-rats (Heterocephalus glaber), some non-breeding males show faster
      growth and are more likely to disperse than others. These differences have been
      suggested to be the result of a specialized developmental strategy leading to
      shorter philopatry and independent breeding, as opposed to extended philopatry as
      non-reproductive helpers. However, it is unclear whether fast-growing males
      disperse sooner than slow-growing males. An alternative explanation is that
      variation in quality between individuals causes high-quality individuals to grow
      quickly and maximize dispersal success without reducing philopatry. Here we show
      that in Damaraland mole-rats (Fukomys damarensis), males that subsequently
      disperse successfully grow faster than other non-reproductive males. This pattern
      is predicted by both hypotheses and does not discriminate between them. However,
      contrary to the suggestion that faster growth represents a developmental
      specialization for early dispersal, fast-growing and slow-growing males remained
      equally long in their natal groups. Our study provides no evidence for adaptive
      divergence in male development leading either to early dispersal or extended
      philopatry. Instead of representing specialized dispersers, fast-growing males of
      this species may be high-quality individuals.

PMID- 29467176
TI  - Correction to 'Phenotypic plasticity in an ant with strong caste-genotype
      association'.

PMID- 29467174
TI  - Mechanotransduction in tumor progression: The dark side of the force.
AB  - Cancer has been characterized as a genetic disease, associated with mutations
      that cause pathological alterations of the cell cycle, adhesion, or invasive
      motility. Recently, the importance of the anomalous mechanical properties of
      tumor tissues, which activate tumorigenic biochemical pathways, has become
      apparent. This mechanical induction in tumors appears to consist of the
      destabilization of adult tissue homeostasis as a result of the reactivation of
      embryonic developmental mechanosensitive pathways in response to pathological
      mechanical strains. These strains occur in many forms, for example,
      hypervascularization in late tumors leads to high static hydrodynamic pressure
      that can promote malignant progression through hypoxia or anomalous interstitial
      liquid and blood flow. The high stiffness of tumors directly induces the
      mechanical activation of biochemical pathways enhancing the cell cycle,
      epithelial-mesenchymal transition, and cell motility. Furthermore, increases in
      solid-stress pressure associated with cell hyperproliferation activate
      tumorigenic pathways in the healthy epithelial cells compressed by the
      neighboring tumor. The underlying molecular mechanisms of the translation of a
      mechanical signal into a tumor inducing biochemical signal are based on
      mechanically induced protein conformational changes that activate classical
      tumorigenic signaling pathways. Understanding these mechanisms will be important
      for the development of innovative treatments to target such mechanical anomalies
      in cancer.

PMID- 29467177
TI  - Extended Vernalization Regulates Inflorescence Fate in Arabis alpina by Stably
      Silencing PERPETUAL FLOWERING1.
AB  - The alpine perennial Arabis alpina initiates flower buds during prolonged
      exposure to cold. In the accession Pajares, we demonstrate that the length of
      vernalization influences flowering time and inflorescence fate but does not
      affect the axillary branches that maintain vegetative growth. The expression of
      floral organ identity genes gradually increases in the main shoot apex during
      vernalization, correlating with an increase in floral commitment. In northern
      Arabidopsis (Arabidopsis thaliana) accessions, the length of vernalization
      modulates the stable silencing of the floral repressor FLOWERING LOCUS C (FLC).
      We demonstrate that expression of PERPETUAL FLOWERING1 (PEP1), the ortholog of
      FLC in A. alpina, is similarly influenced by the duration of the exposure to
      cold. Extended vernalization results in stable silencing of PEP1 in the
      inflorescence. In contrast, insufficient vernalization leads to PEP1 reactivation
      after cold treatment, which correlates with delayed flowering and the appearance
      of floral reversion phenotypes such as bracts and vegetative inflorescence
      branches. Floral reversion phenotypes are reduced in the pep1-1 mutant,
      suggesting that PEP1 regulates the fate of the inflorescence after vernalization.
      The effect of vernalization duration on stable silencing of PEP1 is specific to
      meristems that initiate flowering during cold treatment. Extended vernalization
      fails to silence PEP1 in young seedlings and axillary branches that arise from
      buds initiated during cold treatment, which remain vegetative. We conclude that
      the duration of vernalization in A. alpina differentially regulates PEP1 in the
      inflorescence and axillary branches. PEP1 has a dual role regulating meristem
      fate; it prevents meristems from flowering and antagonizes inflorescence
      development after vernalization.

PMID- 29467178
TI  - A Putative Protein O-Fucosyltransferase Facilitates Pollen Tube Penetration
      through the Stigma-Style Interface.
AB  - During pollen-pistil interactions in angiosperms, the male gametophyte (pollen)
      germinates to produce a pollen tube. To fertilize ovules located within the
      female pistil, the pollen tube must physically penetrate specialized tissues.
      Whereas the process of pollen tube penetration through the pistil has been
      anatomically well described, the genetic regulation remains poorly understood. In
      this study, we identify a novel Arabidopsis (Arabidopsis thaliana) gene, O
      FUCOSYLTRANSFERASE1 (AtOFT1), which plays a key role in pollen tube penetration
      through the stigma-style interface. Semi-in vivo growth assays demonstrate that
      oft1 mutant pollen tubes have a reduced ability to penetrate the stigma-style
      interface, leading to a nearly 2,000-fold decrease in oft1 pollen transmission
      efficiency and a 5- to 10-fold decreased seed set. We also demonstrate that
      AtOFT1 is localized to the Golgi apparatus, indicating its potential role in
      cellular glycosylation events. Finally, we demonstrate that AtOFT1 and other
      similar Arabidopsis genes represent a novel clade of sequences related to
      metazoan protein O-fucosyltransferases and that mutation of residues that are
      important for O-fucosyltransferase activity compromises AtOFT1 function in vivo.
      The results of this study elucidate a physiological function for AtOFT1 in pollen
      tube penetration through the stigma-style interface and highlight the potential
      importance of protein O-glycosylation events in pollen-pistil interactions.

PMID- 29467180
TI  - Ocular neuromyotonia.
AB  - Ocular neuromyotonia is a rare, albeit treatable, ocular motor disorder,
      characterised by recurrent brief episodes of diplopia due to tonic extraocular
      muscle contraction. Ephaptic transmission in a chronically damaged ocular motor
      nerve is the possible underlying mechanism. It usually improves with
      carbamazepine. A 53-year-old woman presented with a 4-month history of recurrent
      episodes of binocular vertical diplopia (up to 40/day), either spontaneously or
      after sustained downward gaze. Between episodes she had a mild left fourth nerve
      palsy. Sustained downward gaze consistently triggered downward left eye tonic
      deviation, lasting around 1 min. MR scan of the brain was normal. She improved on
      starting carbamazepine but developed a rash that necessitated stopping the drug.
      Switching to lacosamide controlled her symptoms.

PMID- 29467181
TI  - In vivo thrombin generation and subsequent APC formation are increased in factor
      V Leiden carriers.

PMID- 29467179
TI  - Toward an integrated map of genetic interactions in cancer cells.
AB  - Cancer genomes often harbor hundreds of molecular aberrations. Such genetic
      variants can be drivers or passengers of tumorigenesis and create vulnerabilities
      for potential therapeutic exploitation. To identify genotype-dependent
      vulnerabilities, forward genetic screens in different genetic backgrounds have
      been conducted. We devised MINGLE, a computational framework to integrate
      CRISPR/Cas9 screens originating from different libraries building on approaches
      pioneered for genetic network discovery in model organisms. We applied this
      method to integrate and analyze data from 85 CRISPR/Cas9 screens in human cancer
      cells combining functional data with information on genetic variants to explore
      more than 2.1 million gene-background relationships. In addition to known
      dependencies, we identified new genotype-specific vulnerabilities of cancer
      cells. Experimental validation of predicted vulnerabilities identified GANAB and
      PRKCSH as new positive regulators of Wnt/beta-catenin signaling. By clustering
      genes with similar genetic interaction profiles, we drew the largest genetic
      network in cancer cells to date. Our scalable approach highlights how diverse
      genetic screens can be integrated to systematically build informative maps of
      genetic interactions in cancer, which can grow dynamically as more data are
      included.

PMID- 29467182
TI  - Somatic IL4R mutations in primary mediastinal large B-cell lymphoma lead to
      constitutive JAK-STAT signaling activation.
AB  - Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct subtype of
      diffuse large B-cell lymphoma thought to arise from thymic medullary B cells.
      Gene mutations underlying the molecular pathogenesis of the disease are
      incompletely characterized. Here, we describe novel somatic IL4R mutations in 15
      of 62 primary cases of PMBCL (24.2%) and in all PMBCL-derived cell lines tested.
      The majority of mutations (11/21; 52%) were hotspot single nucleotide variants in
      exon 8, leading to an I242N amino acid change in the transmembrane domain.
      Functional analyses establish this mutation as gain of function leading to
      constitutive activation of the JAK-STAT pathway and upregulation of downstream
      cytokine expression profiles and B cell-specific antigens. Moreover, expression
      of I242N mutant IL4R in a mouse xenotransplantation model conferred growth
      advantage in vivo. The pattern of concurrent mutations within the JAK-STAT
      signaling pathway suggests additive/synergistic effects of these gene mutations
      contributing to lymphomagenesis. Our data establish IL4R mutations as novel
      driver alterations and provide a strong preclinical rationale for therapeutic
      targeting of JAK-STAT signaling in PMBCL.

PMID- 29467183
TI  - The search for new antithrombotic mechanisms and therapies that may spare
      hemostasis.
AB  - Current antithrombotic drugs, including widely used antiplatelet agents and
      anticoagulants, are associated with significant bleeding risk. Emerging
      experimental evidence suggests that the molecular and cellular mechanisms of
      hemostasis and thrombosis can be separated, thereby increasing the possibility of
      new antithrombotic therapeutic targets with reduced bleeding risk. We review new
      coagulation and platelet targets and highlight the interaction between integrin
      alphaMbeta2 (Mac-1, CD11b/CD18) on leukocytes and GPIbalpha on platelets that
      seems to distinguish thrombosis from hemostasis.

PMID- 29467184
TI  - Low catalase expression confers redox hypersensitivity and identifies an indolent
      clinical behavior in CLL.
AB  - B-cell receptor (BCR) signaling is a key determinant of variable clinical
      behavior and a target for therapeutic interventions in chronic lymphocytic
      leukemia (CLL). Endogenously produced H2O2 is thought to fine-tune the BCR
      signaling by reversibly inhibiting phosphatases. However, little is known about
      how CLL cells sense and respond to such redox cues and what effect they have on
      CLL. We characterized the response of BCR signaling proteins to exogenous H2O2 in
      cells from patients with CLL, using phosphospecific flow cytometry. Exogenous
      H2O2 in the absence of BCR engagement induced a signaling response of BCR
      proteins that was higher in CLL with favorable prognostic parameters and an
      indolent clinical course. We identified low catalase expression as a possible
      mechanism accounting for redox signaling hypersensitivity. Decreased catalase
      could cause an escalated accumulation of exogenous H2O2 in leukemic cells with a
      consequent greater inhibition of phosphatases and an increase of redox signaling
      sensitivity. Moreover, lower levels of catalase were significantly associated
      with a slower progression of the disease. In leukemic cells characterized by
      redox hypersensitivity, we also documented an elevated accumulation of ROS and an
      increased mitochondrial amount. Taken together, our data identified redox
      sensitivity and metabolic profiles that are linked to differential clinical
      behavior in CLL. This study advances our understanding of the redox and signaling
      heterogeneity of CLL and provides the rationale for the development of therapies
      targeting redox pathways in CLL.

PMID- 29467185
TI  - No red blood cell damage and no hemolysis in G6PD-deficient subjects after
      ingestion of low vicine/convicine Vicia faba seeds.

PMID- 29467186
TI  - A pilot study of a Medication Rationalization (MERA) intervention.
AB  - BACKGROUND: Many seriously ill and frail inpatients receive potentially
      inappropriate or harmful medications and do not receive medications for symptoms
      of advanced illness. We developed and piloted an interprofessional Medication
      Rationalization (MERA) approach to deprescribing inappropriate medications and
      prescribing appropriate comfort medications. METHODS: We conducted a single
      centre pilot study of inpatients at risk of 6-month mortality from advanced age
      or morbidity. The MERA team reviewed the patients' medications and made
      recommendations on the basis of guidelines. We measured end points for
      feasibility, acceptability, efficiency and effectiveness. RESULTS: We enrolled 61
      of 115 (53%) eligible patients with a mean age of 79.6 years (standard deviation
      [SD] 11.7 yr). Patients were taking an average of 11.5 (SD 5.2) medications
      before admission and had an average of 2.1 symptoms with greater than 6/10
      severity on the revised Edmonton Symptom Assessment System. The MERA team
      recommended 263 medication changes, of which 223 (85%) were accepted by both the
      medical team and the patient. MERA team's recommendations resulted in the
      discontinuation of 162 medications (mean 3.1 per patient), dose changes for 48
      medications (mean 0.9 per patient) and the addition of 13 medications (mean 0.2
      per patient). Patients who received the MERA intervention stopped significantly
      more inappropriate medications than similar non-MERA comparison patients for whom
      data were collected retrospectively (3.1 v. 0.9 medications per patient, p <
      0.01). The MERA approach was highly acceptable to patients and medical team
      members. INTERPRETATION: The MERA intervention is feasible, acceptable, efficient
      and possibly effective for changing medication use among seriously ill and frail
      elderly inpatients. Scalability and effectiveness may be improved through
      automation and integration with medication reconciliation programs.

PMID- 29467187
TI  - Drosophila Larval Brain Neoplasms Present Tumour-Type Dependent Genome
      Instability.
AB  - Single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) are found
      at different rates in human cancer. To determine if these genetic lesions appear
      in Drosophila tumors we have sequenced the genomes of 17 malignant neoplasms
      caused by mutations in l(3)mbt, brat, aurA, or lgl We have found CNVs and SNPs in
      all the tumors. Tumor-linked CNVs range between 11 and 80 per sample, affecting
      between 92 and 1546 coding sequences. CNVs are in average less frequent in
      l(3)mbt than in brat lines. Nearly half of the CNVs fall within the 10 to 100Kb
      range, all tumor samples contain CNVs larger that 100 Kb and some have CNVs
      larger than 1Mb. The rates of tumor-linked SNPs change more than 20-fold
      depending on the tumor type: at late time points brat, l(3)mbt, and aurA and lgl
      lines present median values of SNPs/Mb of exome of 0.16, 0.48, and 3.6,
      respectively. Higher SNP rates are mostly accounted for by C > A transversions,
      which likely reflect enhanced oxidative stress conditions in the affected tumors.
      Both CNVs and SNPs turn over rapidly. We found no evidence for selection of a
      gene signature affected by CNVs or SNPs in the cohort. Altogether, our results
      show that the rates of CNVs and SNPs, as well as the distribution of CNV sizes in
      this cohort of Drosophila tumors are well within the range of those reported for
      human cancer. Genome instability is therefore inherent to Drosophila malignant
      neoplastic growth at a variable extent that is tumor type dependent.

PMID- 29467188
TI  - Mapping and Predicting Non-Linear Brassica rapa Growth Phenotypes Based on
      Bayesian and Frequentist Complex Trait Estimation.
AB  - Predicting phenotypes based on genotypes and understanding the effects of complex
      multi-locus traits on plant performance requires a description of the underlying
      developmental processes, growth trajectories, and their genomic architecture.
      Using data from Brassica rapa genotypes grown in multiple density settings and
      seasons, we applied a hierarchical Bayesian Function-Valued Trait (FVT) approach
      to fit logistic growth curves to leaf phenotypic data (length and width) and
      characterize leaf development. We found evidence of genetic variation in
      phenotypic plasticity of rate and duration of leaf growth to growing season. In
      contrast, the magnitude of the plastic response for maximum leaf size was
      relatively small, suggesting that growth dynamics vs. final leaf sizes have
      distinct patterns of environmental sensitivity. Consistent with patterns of
      phenotypic plasticity, several QTL-by-year interactions were significant for
      parameters describing leaf growth rates and durations but not leaf size. In
      comparison to frequentist approaches for estimating leaf FVT, Bayesian trait
      estimation resulted in more mapped QTL that tended to have greater average LOD
      scores and to explain a greater proportion of trait variance. We then constructed
      QTL-based predictive models for leaf growth rate and final size using data from
      one treatment (uncrowded plants in one growing season). Models successfully
      predicted non-linear developmental phenotypes for genotypes not used in model
      construction and, due to a lack of QTL-by-treatment interactions, predicted
      phenotypes across sites differing in plant density.

PMID- 29467189
TI  - Synopsis of the SOFL Plant-Specific Gene Family.
AB  - SUPPRESSOR OF PHYB-4#5DOMINANT (sob5-D) was previously identified as a suppressor
      of the phyB-4 long-hypocotyl phenotype in Arabidopsis thaliana Overexpression of
      SOB5 conferred dwarf phenotypes similar to those observed in plants containing
      elevated levels of cytokinin (CK) nucleotides and nucleosides. Two SOB-FIVE- LIKE
      (SOFL) proteins, AtSOFL1 and AtSOFL2, which are more similar at the protein level
      to each other than they are to SOB5, conferred similar phenotypes to the sob5-D
      mutant when overexpressed. We used protein sequences of founding SOFL gene family
      members to perform database searches and identified a total of 289 SOFL homologs
      in genomes of 89 angiosperm species. Phylogenetic analysis results implied that
      the SOFL gene family emerged during the expansion of angiosperms and later
      evolved into four distinct clades. Among the newly identified gene family members
      are four previously unreported Arabidopsis SOFLs Multiple sequence alignment of
      the 289 SOFL protein sequences revealed two highly conserved domains; SOFL-A and
      SOFL-B. We used overexpression and site-directed mutagenesis studies to
      demonstrate that SOFL domains are necessary for SOB5 and AtSOFL1's overexpression
      phenotypes. Examination of the subcellular localization patterns of founding
      Arabidopsis thaliana SOFLs suggested they may be localized in the cytoplasm
      and/or the nucleus. Overall, we report that SOFLs are a plant-specific gene
      family characterized by two conserved domains that are important for function.

PMID- 29467190
TI  - Examination of Signatures of Recent Positive Selection on Genes Involved in Human
      Sialic Acid Biology.
AB  - Sialic acids are nine carbon sugars ubiquitously found on the surfaces of
      vertebrate cells and are involved in various immune response-related processes.
      In humans, at least 58 genes spanning diverse functions, from biosynthesis and
      activation to recycling and degradation, are involved in sialic acid biology.
      Because of their role in immunity, sialic acid biology genes have been
      hypothesized to exhibit elevated rates of evolutionary change. Consistent with
      this hypothesis, several genes involved in sialic acid biology have experienced
      higher rates of non-synonymous substitutions in the human lineage than their
      counterparts in other great apes, perhaps in response to ancient pathogens that
      infected hominins millions of years ago (paleopathogens). To test whether sialic
      acid biology genes have also experienced more recent positive selection during
      the evolution of the modern human lineage, reflecting adaptation to contemporary
      cosmopolitan or geographically-restricted pathogens, we examined whether their
      protein-coding regions showed evidence of recent hard and soft selective sweeps.
      This examination involved the calculation of four measures that quantify changes
      in allele frequency spectra, extent of population differentiation, and haplotype
      homozygosity caused by recent hard and soft selective sweeps for 55 sialic acid
      biology genes using publicly available whole genome sequencing data from 1,668
      humans from three ethnic groups. To disentangle evidence for selection from
      confounding demographic effects, we compared the observed patterns in sialic acid
      biology genes to simulated sequences of the same length under a model of neutral
      evolution that takes into account human demographic history. We found that the
      patterns of genetic variation of most sialic acid biology genes did not
      significantly deviate from neutral expectations and were not significantly
      different among genes belonging to different functional categories. Those few
      sialic acid biology genes that significantly deviated from neutrality either
      experienced soft sweeps or population-specific hard sweeps. Interestingly, while
      most hard sweeps occurred on genes involved in sialic acid recognition, most soft
      sweeps involved genes associated with recycling, degradation and activation,
      transport, and transfer functions. We propose that the lack of signatures of
      recent positive selection for the majority of the sialic acid biology genes is
      consistent with the view that these genes regulate immune responses against
      ancient rather than contemporary cosmopolitan or geographically restricted
      pathogens.

PMID- 29467191
TI  - Targeted next-generation sequencing in blast phase myeloproliferative neoplasms.
AB  - Among 248 consecutive patients with blast phase myeloproliferative neoplasm (MPN
      BP), DNA collected at the time of blast transformation was available in 75
      patients (median age, 66 years; 64% men). MPN-BP followed primary myelofibrosis
      in 39 patients, essential thrombocythemia in 20 patients, and polycythemia vera
      in 16 patients. A myeloid neoplasm-relevant 33-gene panel was used for next
      generation sequencing. Driver mutation distribution was JAK2 57%, CALR 20%, MPL
      9%, and triple-negative 13%. Sixty-four patients (85%) harbored other
      mutations/variants, including 37% with >=3 mutations; most frequent were ASXL1
      47%, TET2 19%, RUNX1 17%, TP53 16%, EZH2 15%, and SRSF2 13%; relative mutual
      exclusivity was expressed by TP53, EZH2, LNK, RUNX1, SRSF2, and NRAS/KRAS
      mutations. Paired chronic-blast phase sample analysis was possible in 19 patients
      and revealed more frequent blast phase acquisition of ASXL1, EZH2, LNK, TET2,
      TP53, and PTPN11 mutations/variants. In multivariable analysis, RUNX1 and PTPN11
      mutations/variants were associated with shorter survival duration; respective
      hazard ratios (HRs) (95% confidence interval [CI]) were 2.1 (95% CI, 1.1-3.8) and
      3.0 (95% CI, 1.1-6.6). An all-inclusive multivariable analysis confirmed the
      prognostic relevance of RUNX1 mutations (HR, 1.9; 95% CI, 1.5-5.5) and also
      showed additional contribution from a treatment strategy that includes transplant
      or induction of complete or near-complete remission (HR, 0.3; 95% CI, 0.2-0.5).
      The current study points to specific mutations that might bear pathogenetic
      relevance for leukemic transformation in MPN and also suggest an adverse survival
      effect of RUNX1 mutations.

PMID- 29467192
TI  - Combination of the low anticoagulant heparin CX-01 with chemotherapy for the
      treatment of acute myeloid leukemia.
AB  - Relapses in acute myelogenous leukemia (AML) are a result of quiescent leukemic
      stem cells (LSCs) in marrow stromal niches, where they resist chemotherapy. LSCs
      employ CXCL12/CXCR4 to home toward protective marrow niches. Heparin disrupts
      CXCL12-mediated sequestration of cells in the marrow. CX-01 is a low
      anticoagulant heparin derivative. In this pilot study, we combined CX-01 with
      chemotherapy for the treatment of AML. Induction consisted of cytarabine and
      idarubicin (7 + 3) with CX-01. Twelve patients were enrolled (median age, 56
      years; 3 women). Three, 5, and 4 patients had good-, intermediate-, and poor-risk
      disease, respectively. Day 14 bone marrows were available on 11 patients and were
      aplastic in all without detectable leukemia. Eleven patients (92%) had
      morphologic complete remission after 1 induction (CR1). Eight patients were alive
      at a median follow-up of 24 months (4 patients in CR1). Three patients received
      an allogeneic stem cell transplant in CR1. Median disease-free survival was 14.8
      months. Median overall survival was not attained at the maximum follow-up time of
      29.4 months. No CX-01-associated serious adverse events occurred. Median day to
      an untransfused platelet count of at least 20 * 109/L was 21. CX-01 is well
      tolerated when combined with intensive therapy for AML and appears associated
      with enhanced count recovery and treatment efficacy.

PMID- 29467193
TI  - Adaptation of Amoeba Plate Test To Recover Legionella Strains from Clinical
      Samples.
AB  - The isolation of Legionella from respiratory samples is the gold standard for
      diagnosis of Legionnaires' disease (LD) and enables epidemiological studies and
      outbreak investigations. The purpose of this work was to adapt and to evaluate
      the performance of an amoebic coculture procedure (the amoeba plate test [APT])
      for the recovery of Legionella strains from respiratory samples, in comparison
      with axenic culture and liquid-based amoebic coculture (LAC). Axenic culture,
      LAC, and APT were prospectively performed with 133 respiratory samples from
      patients with LD. The sensitivities and times to results for the three techniques
      were compared. Using the three techniques, Legionella strains were isolated in
      46.6% (n = 62) of the 133 respiratory samples. The sensitivity of axenic culture
      was 42.9% (n = 57), that of LAC was 30.1% (n = 40), and that of APT was 36.1% (n
      = 48). Seven samples were positive by axenic culture only; for those samples,
      there were <10 colonies in total. Five samples, all sputum samples, were positive
      by an amoebic procedure only (5/5 samples by APT and 2/5 samples by LAC); all had
      overgrowth by oropharyngeal flora with axenic culture. The combination of axenic
      culture with APT yielded a maximal isolation rate (i.e., 46.6%). Overall, the APT
      significantly reduced the median time for Legionella identification to 4 days,
      compared with 7 days for LAC (P < 0.0001). The results of this study support the
      substitution of LAC by APT, which could be implemented as a second-line technique
      for culture-negative samples and samples with microbial overgrowth, especially
      sputum samples. The findings provide a logical basis for further studies in both
      clinical and environmental settings.

PMID- 29467194
TI  - Identification and Characterization of Clostridium difficile Sequence Type 37
      Genotype by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass
      Spectrometry.
AB  - Clostridium difficile multilocus sequence type 37 (ST37), which mainly
      corresponds to ribotype 017, has been a dominant genotype circulating in China.
      In this study, we report the use of matrix-assisted laser desorption ionization
      time of flight mass spectrometry (MALDI-TOF MS) to analyze and characterize 204
      C. difficile clinical isolates, including 49 ST37 and 155 non-ST37 isolates
      collected in China and other countries. The distributions of two major protein
      peaks (m/z 3,242 and 3,286) were significantly different between ST37 and non
      ST37 prototype strains and clinical isolates. This difference was reproducible
      when analysis was performed on different colonies in different runs. This finding
      was repeated and confirmed by both bioMerieux Vitek MS and Bruker Microflex LT
      systems on isolates recovered from a variety of geographic regions worldwide. The
      combination of the two peaks was present in 47 of 49 ST37 isolates, resulting in
      a sensitivity of 95.9%. In contrast, the peak combination was absent in 153 of
      155 non-ST37 isolates, resulting in a specificity of 98.7%. Our results suggest
      that MALDI-TOF MS is a rapid and reliable tool to identify C. difficile genotype
      ST37. Work is in progress to characterize the two molecules having peaks at m/z
      3,242 and 3,286, which appear to be specific to C. difficile genotype ST37.

PMID- 29467195
TI  - Direct Molecular Detection and Genotyping of Borrelia burgdorferi Sensu Lato in
      Cerebrospinal Fluid of Children with Lyme Neuroborreliosis.
AB  - The current diagnostic marker of Lyme neuroborreliosis (LNB), the Borrelia
      burgdorferisensu lato antibody index (AI) in the cerebrospinal fluid (CSF), has
      insufficient sensitivity in the early phase of LNB. We aimed to elucidate the
      diagnostic value of PCR for B. burgdorferisensu lato in CSF from children with
      symptoms suggestive of LNB and to explore B. burgdorferisensu lato genotypes
      associated with LNB in children. Children were prospectively included in
      predefined groups with a high or low likelihood of LNB based on diagnostic
      guidelines (LNB symptoms, CSF pleocytosis, and B. burgdorferisensu lato
      antibodies) or the detection of other causative agents. CSF samples were analyzed
      by two B. burgdorferisensu lato-specific real-time PCR assays and, if B.
      burgdorferisensu lato DNA was detected, were further analyzed by five singleplex
      real-time PCR assays for genotype determination. For children diagnosed as LNB
      patients (58 confirmed and 18 probable) (n = 76) or non-LNB controls (n = 28),
      the sensitivity and specificity of PCR for B. burgdorferisensu lato in CSF were
      46% and 100%, respectively. B. burgdorferisensu lato DNA was detected in 26/58
      (45%) children with AI-positive LNB and in 7/12 (58%) children with AI-negative
      LNB and symptoms of short duration. Among 36 children with detectable B.
      burgdorferisensu lato DNA, genotyping indicated Borrelia garinii (n = 27) and non
      B. garinii (n = 1) genotypes, while 8 samples remained untyped. Children with LNB
      caused by B. garinii did not have a distinct clinical picture. The rate of
      detection of B. burgdorferisensu lato DNA in the CSF of children with LNB was
      higher than that reported previously. PCR for B. burgdorferisensu lato could be a
      useful supplemental diagnostic tool in unconfirmed LNB cases with symptoms of
      short duration. B. garinii was the predominant genotype in children with LNB.

PMID- 29467196
TI  - Specific Activation of the Alternative Cardiac Promoter of Cacna1c by the
      Mineralocorticoid Receptor.
AB  - RATIONALE: The MR (mineralocorticoid receptor) antagonists belong to the current
      therapeutic armamentarium for the management of cardiovascular diseases, but the
      mechanisms conferring their beneficial effects are poorly understood. Part of the
      cardiovascular effects of MR is because of the regulation of L-type Cav1.2 Ca2+
      channel expression, which is generated by tissue-specific alternative promoters
      as a long cardiac or short vascular N-terminal transcripts. OBJECTIVE: To analyze
      the molecular mechanisms by which aldosterone, through MR, modulates Cav1.2
      expression and function in a tissue-specific manner. METHODS AND RESULTS: In
      primary cultures of neonatal rat ventricular myocytes, aldosterone exposure for
      24 hours increased in a concentration-dependent manner long cardiac Cav1.2 N
      terminal transcripts expression at both mRNA and protein levels, correlating with
      enhanced concentration-, time-, and MR-dependent P1-promoter activity. In silico
      analysis and mutagenesis identified MR interaction with both specific activating
      and repressing DNA-binding elements on the P1-promoter. The relevance of this
      regulation is confirmed both ex and in vivo in transgenic mice harboring the
      luciferase reporter gene under the control of the cardiac P1-promoter. Moreover,
      we show that this cis-regulatory mechanism is not limited to the heart. Indeed,
      in smooth muscle cells from different vascular beds, in which the short vascular
      Cav1.2 N-terminal transcripts is normally the major isoform, we found that MR
      signaling activates long cardiac Cav1.2 N-terminal transcripts expression through
      P1-promoter activation, leading to vascular contractile dysfunction. These
      results were further corroborated in hypertensive aldosterone/salt rodent models,
      showing notably a positive correlation between blood pressure and cardiac P1
      promoter activity in aorta. This new vascular long cardiac Cav1.2 N-terminal
      transcripts molecular signature reduced sensitivity to the Ca2+ channel blocker,
      nifedipine, in aldosterone-treated vessels. CONCLUSIONS: Our results reveal that
      MR acts as a transcription factor to translate aldosterone signal into specific
      cardiac P1-promoter activation that might influence the therapeutic outcome of
      cardiovascular diseases.

PMID- 29467197
TI  - Reflection of Cardioprotection by Remote Ischemic Perconditioning in Attenuated
      ST-Segment Elevation During Ongoing Coronary Occlusion in Pigs: Evidence for
      Cardioprotection From Ischemic Injury.
AB  - RATIONALE: Reduction of infarct size by remote ischemic perconditioning (perRIC)
      is evident only after several hours reperfusion. OBJECTIVE: To develop a
      potential real-time estimate of cardioprotection by perRIC, we have analyzed the
      time course of ST-segment elevation. METHODS AND RESULTS: Anesthetized open-chest
      pigs were subjected to 60-minute coronary occlusion and 180-minute reperfusion
      (placebo; n=19). PerRIC (n=18; 4*5 min/5 min hindlimb occlusion/reperfusion) was
      induced 20 minutes after coronary occlusion. Regional myocardial blood flow was
      measured with microspheres, areas of no-reflow with thioflavin-S, area at risk
      with blue dye, and infarct size with triphenyl tetrazolium chloride staining.
      Phosphorylation of protein kinase B alpha/beta/gamma, extracellular signal
      regulated kinase 1/2, and signal transducer and activator of transcription 3 was
      determined by Western blot. ST-segment elevation was analyzed in a V2-like ECG
      lead at baseline, 5- and 55-minute coronary occlusion, and 10-, 30-, 60-, and 120
      minute reperfusion. Transmural blood flow at 5-minute coronary occlusion was not
      different between perRIC (0.029+/-0.015 mL/min per gram; mean+/-SD) and placebo
      (0.024+/-0.018 mL/min per gram) as was area at risk (perRIC: 24+/-6% of the left
      ventricle; placebo: 21+/-4%). Areas of no-reflow tended to be smaller with perRIC
      (9+/-12% of area at risk versus 15+/-14% with placebo; P=0.13). Infarct size with
      perRIC was 23+/-12% of area at risk versus 40+/-11% with placebo (P<0.001).
      PerRIC increased phosphorylation of signal transducer and activator of
      transcription 3 at 120-minute reperfusion by 196+/-142% versus 109+/-120% with
      placebo (P=0.047). The time courses of ST-segment elevation in perRIC and placebo
      protocols, respectively, were different (P=0.017). With similar ST-segment
      elevation at 5-minute coronary occlusion (perRIC 282+/-34 uV; placebo 259+/-28
      uV), partial recovery of ST-segment elevation between 5- and 55-minute coronary
      occlusion was more pronounced with perRIC than placebo (by 111+/-84 versus 15+/
      94 uV; P=0.028). CONCLUSION: Infarct size reduction by perRIC is reflected in the
      ST-segment elevation during coronary occlusion in pigs, supporting the notion of
      protection from ischemic injury.

PMID- 29467199
TI  - Living with breathlessness: a systematic literature review and qualitative
      synthesis.
AB  - What is the experience of people living with breathlessness due to medical
      conditions, those caring for them and those treating them, with regard to quality
      of life and the nature of clinical interactions?Electronic databases (Ovid
      MEDLINE, Embase, CINAHL Plus and PsycINFO) were searched (January 1987 to October
      2017; English language), for qualitative studies exploring the experience of
      chronic breathlessness (patients, carers and clinicians). Two independent
      reviewers screened titles, abstracts and papers retrieved against inclusion
      criteria. Disagreements were resolved with a third reviewer. Primary qualitative
      data were extracted and synthesised using thematic synthesis.Inclusion and
      synthesis of 101 out of 2303 international papers produced four descriptive
      themes: 1) widespread effects of breathlessness; 2) coping; 3) help-seeking
      behaviour; and 4) clinicians' responsiveness to the symptom of breathlessness.
      The themes were combined to form the concept of "breathing space", to show how
      engaged coping and appropriate help-seeking (patient) and attention to symptom
      (clinician) helps maximise the patient's quality of living with
      breathlessness.Breathlessness has widespread impact on both patient and carer and
      affects breathing space. The degree of breathing space is influenced by
      interaction between the patient's coping style, their help-seeking behaviour and
      their clinician's responsiveness to breathlessness itself, in addition to
      managing the underlying disease.

PMID- 29467198
TI  - Endothelial TFEB (Transcription Factor EB) Positively Regulates Postischemic
      Angiogenesis.
AB  - RATIONALE: Postischemic angiogenesis is critical to limit the ischemic tissue
      damage and improve the blood flow recovery. The regulation and the underlying
      molecular mechanisms of postischemic angiogenesis are not fully unraveled. TFEB
      (transcription factor EB) is emerging as a master gene for autophagy and lysosome
      biogenesis. However, the role of TFEB in vascular disease is less understood.
      OBJECTIVE: We aimed to determine the role of endothelial TFEB in postischemic
      angiogenesis and its underlying molecular mechanism. METHODS AND RESULTS: In
      primary human endothelial cells (ECs), serum starvation induced TFEB nuclear
      translocation. VEGF (vascular endothelial growth factor) increased TFEB
      expression level and nuclear translocation. Utilizing genetically engineered EC
      specific TFEB transgenic and KO (knockout) mice, we investigated the role of TFEB
      in postischemic angiogenesis in the mouse hindlimb ischemia model. We observed
      improved blood perfusion and increased capillary density in the EC-specific TFEB
      transgenic mice compared with the wild-type littermates. Furthermore, blood flow
      recovery was attenuated in EC-TFEB KO mice compared with control mice. In aortic
      ring cultures, the TFEB transgene significantly increased vessel sprouting,
      whereas TFEB deficiency impaired the vessel sprouting. In vitro, adenovirus
      mediated TFEB overexpression promoted EC tube formation, migration, and survival,
      whereas siRNA-mediated TFEB knockdown had the opposite effect. Mechanistically,
      TFEB activated AMPK (AMP-activated protein kinase)-alpha signaling and
      upregulated autophagy. Through inactivation of AMPKalpha or inhibition of
      autophagy, we demonstrated that the AMPKalpha and autophagy are necessary for
      TFEB to regulate angiogenesis in ECs. Finally, the positive effect of TFEB on
      AMPKalpha activation and EC tube formation was mediated by TFEB-dependent
      transcriptional upregulation of MCOLN1 (mucolipin-1). CONCLUSIONS: In summary,
      our data demonstrate that TFEB is a positive regulator of angiogenesis through
      activation of AMPKalpha and autophagy, suggesting that TFEB constitutes a novel
      molecular target for ischemic vascular disease.

PMID- 29467200
TI  - Effectiveness versus efficacy trials in COPD: how study design influences
      outcomes and applicability.
AB  - Guidelines for chronic obstructive pulmonary disease (COPD) management are based
      largely on results from double-blind randomised controlled trials (RCTs) of
      efficacy. These trials have high internal validity and test whether a drug is
      efficacious, but they are conducted in highly selected populations that may
      differ significantly from patients with COPD seen in routine practice.We compared
      the baseline characteristics, healthcare use and outcomes between the Salford
      Lung Study (SLS), an open-label effectiveness RCT, with six recent large-scale
      efficacy RCTs. We also calculated the proportion of SLS patients who would have
      been eligible for inclusion in an efficacy RCT by applying the inclusion criteria
      used in efficacy trials of combination treatments.SLS patients were older,
      included more females and more current smokers, had more comorbidities (including
      asthma), and had more often experienced exacerbations prior to inclusion. In the
      SLS, rates of moderate or severe exacerbations, incidence of overall serious
      adverse events (SAEs), and SAEs of pneumonia were more frequent. A maximum of 30%
      of patients enrolled in the SLS would have been eligible for a phase IIIa
      regulatory exacerbation study.Patients in large COPD efficacy RCTs have limited
      representativeness compared with an effectiveness trial. This should be
      considered when interpreting efficacy RCT outcomes and their inclusion into
      guidelines.

PMID- 29467201
TI  - Small airways dysfunction: the link between allergic rhinitis and allergic
      asthma.
AB  - Abnormal airway reactivity and overproduction of nitric oxide (NO) occurring in
      small airways have been found in asthma. If the "one airway, one disease" concept
      is consistent, such dysfunctions should also be detected in the peripheral
      airways of patients suffering from allergic rhinitis.We investigated whether
      peripheral airway reactivity and NO overproduction could be documented in distal
      airways in patients with allergic rhinitis. Exhaled NO fraction (FeNO) and the
      slope (S) of phase III of the single-breath washout test (SBWT) of helium (He)
      and sulfur hexafluoride (SF6) were measured in 31 patients with allergic asthma,
      23 allergic rhinitis patients and 24 controls, before and after sputum induction.
      SBWT is sensitive to airway calibre change occurring in the lung periphery.The
      FeNO decrease was more significant in asthma and rhinitis than in controls (
      55.1% and -50.0%, respectively, versus -40.8%) (p=0.007 and p=0.029,
      respectively). SSF6 and SHe increased in all groups. Change in SHe (DeltaSHe) >
      DeltaSSF6 was observed in rhinitis (p=0.004) and asthma (p<0.001), whereas
      DeltaSSF6 = DeltaSHe in controls (p=0.431).This study provides evidence of
      peripheral airway dysfunction in patients with allergic rhinitis quite similar to
      that described in asthma. Furthermore, a large proportion of the increased NO
      production reported in allergic rhinitis appears to originate in the peripheral
      airways.

PMID- 29467203
TI  - Sarcoidosis mortality in Sweden: a population-based cohort study.
AB  - We aimed to investigate sarcoidosis mortality in a large, population-based
      cohort, taking into account disease heterogeneity.Individuals with incident
      sarcoidosis (n=8207) were identified from the Swedish National Patient Register
      using International Classification of Disease codes (2003-2013). In a subset,
      cases receiving treatment +/-3 months from diagnosis were identified from the
      Prescribed Drug Register. Nonsarcoidosis comparators from the general population
      were matched to cases 10:1 on birth year, sex and county. Individuals were
      followed for all-cause death in the Cause of Death Register. Adjusted mortality
      rates, rate differences and hazard ratios (HRs) were estimated, stratifying by
      age, sex and treatment status.The mortality rate was 11.0 per 1000 person-years
      in sarcoidosis versus 6.7 in comparators (rate difference 2.7 per 1000 person
      years). The HR for death was 1.61 (95% CI 1.47-1.76), with no large variation by
      age or sex. For cases not receiving treatment within the first 3 months, the HR
      was 1.13 (95% CI 0.94-1.35). The HR was 2.34 (95% CI 1.99-2.75) for those
      receiving treatment.Individuals with sarcoidosis are at a higher risk of death
      compared to the general population. For the majority, the increased risk is
      small. However, patients whose disease leads to treatment around diagnosis have a
      two-fold increased risk of death. Future interventions should focus on this
      vulnerable group.

PMID- 29467204
TI  - The role of air pollution and lung function in cognitive impairment.
AB  - Air pollution has been associated with impaired lung and cognitive function,
      especially impairment in visuo-construction performance (VCP). In this article,
      we evaluate whether the effect of air pollution on VCP is mediated by lung
      function.We used data from the SALIA cohort (baseline 1985-1994 and follow-up
      2007-2010) including 587 women aged 55 years at baseline. Particulate matter (PM)
      and nitrogen dioxide (NO2) exposures at baseline were estimated via land-use
      regression models. Lung function was characterised by averages between baseline
      and follow-up. We used age- and height-controlled Global Lung Initiative (GLI) z
      scores of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and
      FEV1/FVC. VCP was assessed at follow-up with the CERAD-Plus neuropsychological
      test battery and causal mediation analysis was conducted.An increase of one
      interquartile range in FEV1 and FVC was positively associated with VCP (beta=0.18
      (95% CI 0.02-0.34) and beta=0.23 (95% CI 0.07-0.39), respectively). The
      proportion of the association between NO2 on VCP mediated by FEV1 was 6.2% and
      this was higher in never smokers (7.2%) and non-carriers of the APOE-epsilon4
      allele (11.2%). However, none of the mediations were statistically significant.In
      conclusion, air pollution associated VCP was partially mediated by lung function.
      Further studies on the mechanisms underlying this pathway are required to develop
      new strategies to prevent air pollution induced cognitive impairment.

PMID- 29467202
TI  - Primary ciliary dyskinesia with normal ultrastructure: three-dimensional
      tomography detects absence of DNAH11.
AB  - In primary ciliary dyskinesia (PCD), motile ciliary dysfunction arises from
      ciliary defects usually confirmed by transmission electron microscopy (TEM). In
      30% of patients, such as those with DNAH11 mutations, apparently normal
      ultrastructure makes diagnosis difficult. Genetic analysis supports diagnosis,
      but may not identify definitive causal variants. Electron tomography, an
      extension of TEM, produces three-dimensional ultrastructural ciliary models with
      superior resolution to TEM. Our hypothesis is that tomography using existing
      patient samples will enable visualisation of DNAH11-associated ultrastructural
      defects. Dual axis tomograms from araldite-embedded nasal cilia were collected in
      13 PCD patients with normal ultrastructure (DNAH11 n=7, HYDIN n=2, CCDC65 n=3 and
      DRC1 n=1) and six healthy controls, then analysed using IMOD and Chimera
      software.DNAH11 protein is localised to the proximal ciliary region. Within this
      region, electron tomography indicated a deficiency of >25% of proximal outer
      dynein arm volume in all patients with DNAH11 mutations (n=7) compared to other
      patients with PCD and normal ultrastructure (n=6) and healthy controls (n=6).
      DNAH11 mutations cause a shared abnormality in ciliary ultrastructure previously
      undetectable by TEM. Advantageously, electron tomography can be used on existing
      diagnostic samples and establishes a structural abnormality where ultrastructural
      studies were previously normal.

PMID- 29467205
TI  - Relapse-free cure from multidrug-resistant tuberculosis in Germany.

PMID- 29467206
TI  - The incidence of tuberculosis among adolescents and young adults: a global
      estimate.
AB  - Historical data show that the risk of tuberculosis increases dramatically during
      adolescence, and young people face unique challenges in terms of case detection
      and effective treatment. However, little is known about the burden of
      tuberculosis among young people in the modern era. This study aimed to provide
      the first estimates of the global and regional incidence of tuberculosis among
      young people aged 10-24 years.Using the World Health Organization (WHO) database
      of tuberculosis notifications for 2012, we estimated the burden of tuberculosis
      among young people by WHO region. Adjustments were made for incomplete age
      disaggregation and underreporting, using supplementary data from several
      countries representing diverse tuberculosis epidemics.We estimate that 1.78
      million (uncertainty interval (UI) 1.23-3.00 million) young people developed
      tuberculosis in 2012, accounting for 17% of all new tuberculosis cases globally.
      Young people in the WHO South East Asian Region (721 000, UI 473 000-1.35
      million) and the WHO African Region (534 000, UI 359 000-912 000) experienced the
      greatest number of tuberculosis episodes.Young people suffer a considerable
      burden of tuberculosis. Age-specific burden of disease estimation for this age
      group is complicated by incomplete age disaggregation of tuberculosis data,
      highlighting the importance of continued surveillance system strengthening.

PMID- 29467207
TI  - Sex differences and factors influencing the duration of the QT interval in
      patients on anti-tuberculosis therapy.

PMID- 29467208
TI  - Progress in the management of IPF-related acute exacerbations: a goal for
      patients, respirologists and intensivists.

PMID- 29467209
TI  - Revising our approach to conducting therapeutic clinical research in COPD.

PMID- 29467210
TI  - Progress in the management of IPF-related acute exacerbations: a goal for
      patients, respirologists and intensivists.

PMID- 29467211
TI  - Adolescents and young adults: a neglected population group for tuberculosis
      surveillance.

PMID- 29467212
TI  - Intravital Multiphoton Microscopy with Fluorescent Bile Salts in Rats as an In
      Vivo Biomarker for Hepatobiliary Transport Inhibition.
AB  - The bile salt export pump (BSEP) is expressed at the canalicular domain of
      hepatocytes, where it mediates the elimination of monovalent bile salts into the
      bile. Inhibition of BSEP is considered a susceptibility factor for drug-induced
      liver injury that often goes undetected during nonclinical testing. Although in
      vitro assays exist for screening BSEP inhibition, a reliable and specific method
      for confirming Bsep inhibition in vivo would be a valuable follow up to a BSEP
      screening strategy, helping to put a translatable context around in vitro
      inhibition data, incorporating processes such as metabolism, protein binding, and
      other exposure properties that are lacking in most in vitro BSEP models. Here, we
      describe studies in which methods of quantitative intravital microscopy were used
      to identify dose-dependent effects of two known BSEP/Bsep inhibitors, 2-[4-[4
      (butylcarbamoyl)-2-[(2,4-dichlorophenyl)sulfonylamino]phenoxy]-3
      methoxyphenyl]acetic acid (AMG-009) and bosentan, on hepatocellular transport of
      the fluorescent bile salts cholylglycyl amidofluorescein and cholyl-lysyl
      fluorescein in rats. Results of these studies demonstrate that the intravital
      microscopy approach is capable of detecting Bsep inhibition at drug doses well
      below those found to increase serum bile acid levels, and also indicate that
      basolateral efflux transporters play a significant role in preventing cytosolic
      accumulation of bile acids under conditions of Bsep inhibition in rats. Studies
      of this kind can both improve our understanding of exposures needed to inhibit
      Bsep in vivo and provide unique insights into drug effects in ways that can
      improve our ability interpret animal studies for the prediction of human drug
      hepatotoxicity.

PMID- 29467213
TI  - Rare Variants in the ABCG2 Promoter Modulate In Vivo Activity.
AB  - ABCG2 encodes the breast cancer resistance protein (BCRP), an efflux membrane
      transporter important in the detoxification of xenobiotics. In the present study,
      the basal activity of the ABCG2 promoter in liver, kidney, intestine, and breast
      cell lines was examined using luciferase reporter assays. The promoter activities
      of reference and variant ABCG2 sequences were compared in human hepatocellular
      carcinoma cell (HepG2), human embryonic kidney cell (HEK293T), human colorectal
      carcinoma cell (HCT116), and human breast adenocarcinoma cell (MCF-7) lines. The
      ABCG2 promoter activity was strongest in the kidney and intestine cell lines.
      Four variants in the basal ABCG2 promoter (rs76656413, rs66664036, rs139256004,
      and rs59370292) decreased the promoter activity by 25%-50% in at least three of
      the four cell lines. The activity of these four variants was also examined in
      vivo using the hydrodynamic tail vein assay, and two single nucleotide
      polymorphisms (rs76656413 and rs59370292) significantly decreased in vivo liver
      promoter activity by 50%-80%. Electrophoretic mobility shift assays confirmed a
      reduction in nuclear protein binding to the rs59370292 variant probe, whereas the
      rs76656413 probe had a shift in transcription factor binding specificity.
      Although both rs59370292 and rs76656413 are rare variants in all populations,
      they could contribute to patient-level variation in ABCG2 expression in the
      kidney, liver, and intestine.

PMID- 29467214
TI  - Hepatic Transport of 25-Hydroxyvitamin D3 Conjugates: A Mechanism of 25
      Hydroxyvitamin D3 Delivery to the Intestinal Tract.
AB  - Vitamin D3 is an important prohormone critical for maintaining calcium and
      phosphate homeostasis in the body and regulating drug-metabolizing enzymes and
      transporters. 25-Hydroxyvitamin D3 (25OHD3), the most abundant circulating
      metabolite of vitamin D3, is further transformed to the biologically active
      metabolite 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) by CYP27B1 in the
      kidney and extrarenal tissues, and to nonactive metabolites by other cytochrome
      P450 enzymes. In addition, 25OHD3 undergoes sulfation and glucuronidation in the
      liver, forming two major conjugative metabolites, 25OHD3-3-O-sulfate (25OHD3-S)
      and 25OHD3-3-O-glucuronide (25OHD3-G), both of which were detected in human blood
      and bile. Considering that the conjugates excreted into the bile may be
      circulated to and reabsorbed from the intestinal lumen, deconjugated to 25OHD3,
      and then converted to 1alpha,25-(OH)2D3, exerting local intestinal cellular
      effects, it is crucial to characterize enterohepatic transport mechanisms of
      25OHD3-S and 25OHD3-G, and thereby understand and predict mechanisms of
      interindividual variability in mineral homeostasis. In the present study, with
      plasma membrane vesicle and cell-based transport studies, we showed that 25OHD3-G
      is a substrate of multidrug resistance proteins 2 and 3, OATP1B1, and OATP1B3,
      and that 25OHD3-S is probably a substrate of breast cancer resistance protein,
      OATP2B1, and OATP1B3. We also demonstrated sinusoidal and canalicular efflux of
      both conjugates using sandwich-cultured human hepatocytes. Given substantial
      expression of these transporters in liver hepatocytes and intestinal enterocytes,
      this study demonstrates for the first time that transporters could play important
      roles in the enterohepatic circulation of 25OHD3 conjugates, providing an
      alternative pathway of 25OHD3 delivery to the intestinal tract, which could be
      critical for vitamin D receptor-dependent gene regulation in enterocytes.

PMID- 29467215
TI  - Identification of Intestinal UDP-Glucuronosyltransferase Inhibitors in Green Tea
      (Camellia sinensis) Using a Biochemometric Approach: Application to Raloxifene as
      a Test Drug via In Vitro to In Vivo Extrapolation.
AB  - Green tea (Camellia sinensis) is a popular beverage worldwide, raising concern
      for adverse interactions when co-consumed with conventional drugs. Like many
      botanical natural products, green tea contains numerous polyphenolic constituents
      that undergo extensive glucuronidation. As such, the UDP-glucuronosyltransferases
      (UGTs), particularly intestinal UGTs, represent potential first-pass targets for
      green tea-drug interactions. Candidate intestinal UGT inhibitors were identified
      using a biochemometrics approach, which combines bioassay and chemometric data.
      Extracts and fractions prepared from four widely consumed teas were screened (20
      180 MUg/ml) as inhibitors of UGT activity (4-methylumbelliferone glucuronidation)
      in human intestinal microsomes; all demonstrated concentration-dependent
      inhibition. A biochemometrics-identified fraction rich in UGT inhibitors from a
      representative tea was purified further and subjected to second-stage
      biochemometric analysis. Five catechins were identified as major constituents in
      the bioactive subfractions and prioritized for further evaluation. Of these
      catechins, (-)-epicatechin gallate and (-)-epigallocatechin gallate showed
      concentration-dependent inhibition, with IC50 values (105 and 59 MUM,
      respectively) near or below concentrations measured in a cup (240 ml) of tea (66
      and 240 MUM, respectively). Using the clinical intestinal UGT substrate
      raloxifene, the Ki values were ~1.0 and 2.0 MUM, respectively. Using estimated
      intestinal lumen and enterocyte inhibitor concentrations, a mechanistic static
      model predicted green tea to increase the raloxifene plasma area under the curve
      up to 6.1- and 1.3-fold, respectively. Application of this novel approach, which
      combines biochemometrics with in vitro-in vivo extrapolation, to other natural
      product-drug combinations will refine these procedures, informing the need for
      further evaluation via dynamic modeling and clinical testing.

PMID- 29467216
TI  - Molecular basis for sterol transport by StART-like lipid transfer domains.
AB  - Lipid transport proteins at membrane contact sites, where two organelles are
      closely apposed, play key roles in trafficking lipids between cellular
      compartments while distinct membrane compositions for each organelle are
      maintained. Understanding the mechanisms underlying non-vesicular lipid
      trafficking requires characterization of the lipid transporters residing at
      contact sites. Here, we show that the mammalian proteins in the lipid transfer
      proteins anchored at a membrane contact site (LAM) family, called GRAMD1a-c,
      transfer sterols with similar efficiency as the yeast orthologues, which have
      known roles in sterol transport. Moreover, we have determined the structure of a
      lipid transfer domain of the yeast LAM protein Ysp2p, both in its apo-bound and
      sterol-bound forms, at 2.0 A resolution. It folds into a truncated version of the
      steroidogenic acute regulatory protein-related lipid transfer (StART) domain,
      resembling a lidded cup in overall shape. Ergosterol binds within the cup, with
      its 3-hydroxy group interacting with protein indirectly via a water network at
      the cup bottom. This ligand binding mode likely is conserved for the other LAM
      proteins and for StART domains transferring sterols.

PMID- 29467219
TI  - Expression of LDLRs (Low-Density Lipoprotein Receptors), Dyslipidemia Severity,
      and Response to PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Inhibition
      in Homozygous Familial Hypercholesterolemia: Connecting the Dots.

PMID- 29467217
TI  - HP1alpha targets the chromosomal passenger complex for activation at
      heterochromatin before mitotic entry.
AB  - The chromosomal passenger complex (CPC) is directed to centromeres during mitosis
      via binding to H3T3ph and Sgo1. Whether and how heterochromatin protein 1alpha
      (HP1alpha) influences CPC localisation and function during mitotic entry is less
      clear. Here, we alter HP1alpha dynamics by fusing it to a CENP-B DNA-binding
      domain. Tethered HP1 strongly recruits the CPC, destabilising kinetochore
      microtubule interactions and activating the spindle assembly checkpoint. During
      mitotic exit, the tethered HP1 traps active CPC at centromeres. These HP1-CPC
      clusters remain catalytically active throughout the subsequent cell cycle. We
      also detect interactions between endogenous HP1 and the CPC during G2 HP1alpha
      and HP1gamma cooperate to recruit the CPC to active foci in a CDK1-independent
      process. Live cell tracking with Fab fragments reveals that H3S10ph appears well
      before H3T3 is phosphorylated by Haspin kinase. Our results suggest that HP1 may
      concentrate and activate the CPC at centromeric heterochromatin in G2 before
      Aurora B-mediated phosphorylation of H3S10 releases HP1 from chromatin and allows
      pathways dependent on H3T3ph and Sgo1 to redirect the CPC to mitotic centromeres.

PMID- 29467220
TI  - Is It Time for New Thinking About High-Density Lipoprotein?

PMID- 29467218
TI  - Regenerative proliferation of differentiated cells by mTORC1-dependent
      paligenosis.
AB  - In 1900, Adami speculated that a sequence of context-independent energetic and
      structural changes governed the reversion of differentiated cells to a
      proliferative, regenerative state. Accordingly, we show here that differentiated
      cells in diverse organs become proliferative via a shared program. Metaplasia
      inducing injury caused both gastric chief and pancreatic acinar cells to decrease
      mTORC1 activity and massively upregulate lysosomes/autophagosomes; then increase
      damage associated metaplastic genes such as Sox9; and finally reactivate mTORC1
      and re-enter the cell cycle. Blocking mTORC1 permitted autophagy and metaplastic
      gene induction but blocked cell cycle re-entry at S-phase. In kidney and liver
      regeneration and in human gastric metaplasia, mTORC1 also correlated with
      proliferation. In lysosome-defective Gnptab-/- mice, both metaplasia-associated
      gene expression changes and mTORC1-mediated proliferation were deficient in
      pancreas and stomach. Our findings indicate differentiated cells become
      proliferative using a sequential program with intervening checkpoints: (i)
      differentiated cell structure degradation; (ii) metaplasia- or progenitor
      associated gene induction; (iii) cell cycle re-entry. We propose this program,
      which we term "paligenosis", is a fundamental process, like apoptosis, available
      to differentiated cells to fuel regeneration following injury.

PMID- 29467222
TI  - Letter by Sonkar et al Regarding Article, "Class III PI3K Positively Regulates
      Platelet Activation and Thrombosis via PI(3)P-Directed Function of NADPH
      Oxidase".

PMID- 29467221
TI  - Vascular Development.
AB  - The vascular system forms as a branching network of endothelial cells that
      acquire identity as arterial, venous, hemogenic, or lymphatic. Endothelial
      specification depends on gene targets transcribed by Ets domain-containing
      factors, including Ets variant gene 2 (Etv2), together with the activity of
      chromatin-remodeling complexes containing Brahma-related gene-1 (Brg1). Once
      specified and assembled into vessels, mechanisms regulating lumen diameter and
      axial growth ensure that the structure of the branching vascular network matches
      the need for perfusion of target tissues. In addition, blood vessels provide
      important morphogenic cues that guide or direct the development of organs forming
      around them. As the embryo grows and lumen diameters increase, smooth muscle
      cells wrap around the nascent vessel walls to provide mechanical strength and
      vasomotor control of the circulation. Increasing mechanical stretch and wall
      strain promote smooth muscle cell differentiation via coupling of actin
      cytoskeletal remodeling to myocardin and serum response factor-dependent
      transcription. Remodeling of artery walls by developmental signaling pathways
      reappears in postnatal blood vessels during physiological and pathological
      adaptation to vessel wall injury, inflammation, or chronic hypoxia. Recent
      reports providing insights into major steps in vascular development are reviewed
      here with a particular emphasis on studies that have been recently published in
      Arteriosclerosis, Thrombosis, and Vascular Biology.

PMID- 29467223
TI  - Response by Liu and Hu to Letter Regarding Article, "Class III PI3K Positively
      Regulates Platelet Activation and Thrombosis via PI(3)P-Directed Function of
      NADPH Oxidase".

PMID- 29467224
TI  - Introduction to the Thematic Minireview Series: Autophagy.
AB  - Autophagy is a highly conserved, tightly regulated cellular process that degrades
      intracellular constituents via lysosomes. Autophagy mediates many normal cellular
      functions and is dysregulated in numerous diseases. This Thematic Series consists
      of five Minireviews that highlight selected topics of current autophagy research
      ranging from the molecular mechanisms and regulation of autophagy to the roles of
      autophagy in health and disease.

PMID- 29467225
TI  - The transmembrane protein TMEPAI induces myeloma cell apoptosis by promoting
      degradation of the c-Maf transcription factor.
AB  - TMEPAI (transmembrane prostate androgen-induced protein, also called prostate
      transmembrane protein, androgen-induced 1 (PMEPA1)) is a type I transmembrane
      (TM) protein, but its cellular function is largely unknown. Here, studying
      factors influencing the stability of c-Maf, a critical transcription factor in
      multiple myeloma (MM), we found that TMEPAI induced c-Maf degradation. We
      observed that TMEPAI recruited NEDD4 (neural precursor cell expressed,
      developmentally down-regulated 4), a WW domain-containing ubiquitin ligase, to c
      Maf, leading to its degradation through the proteasomal pathway. Further
      investigation revealed that TMEPAI interacts with NEDD4 via its conserved PY
      motifs. Alanine substitution or deletion of these motifs abrogated the TMEPAI
      complex formation with NEDD4, resulting in failed c-Maf degradation.
      Functionally, TMEPAI suppressed the transcriptional activity of c-Maf. Of note,
      increased TMEPAI expression was positively associated with the overall survival
      of MM patients. Moreover, TMEPAI was down-regulated in MM cells, and re
      expression of TMEPAI induced MM cell apoptosis. In conclusion, this study
      highlights that TMEPAI decreases c-Maf stability by recruiting the ubiquitin
      ligase NEDD4 to c-Maf for proteasomal degradation. Our findings suggest that the
      restoration of functional TMEPA1 expression may represent a promising
      complementary therapeutic strategy for treating patients with MM.

PMID- 29467226
TI  - E4BP4/NFIL3 modulates the epigenetically repressed RAS effector RASSF8 function
      through histone methyltransferases.
AB  - RAS proteins are major human oncogenes, and most of the studies are focused on
      enzymatic RAS effectors. Recently, nonenzymatic RAS effectors (RASSF, RAS
      association domain family) have garnered special attention because of their tumor
      suppressive properties in contrast to the oncogenic potential of the classical
      enzymatic RAS effectors. Whereas most members of RASSF family are deregulated by
      promoter hypermethylation, RASSF8 promoter remains unmethylated in many cancers
      but the mechanism(s) of its down-regulation remains unknown. Here, we unveil
      E4BP4 as a critical transcriptional modulator repressing RASSF8 expression
      through histone methyltransferases, G9a and SUV39H1. In line with these
      observations, we noticed a negative correlation of RASSF8 and E4BP4 expression in
      primary breast tumor samples. In addition, our data provide evidence that E4BP4
      attenuates RASSF8-mediated anti-proliferation and apoptosis, shedding mechanistic
      insights into RASSF8 down-regulation in breast cancers. Collectively, our study
      provides a better understanding on the epigenetic regulation of RASSF8 function
      and implicates the development of better treatment strategies.

PMID- 29467228
TI  - Brain cytoplasmic RNA 1 suppresses smooth muscle differentiation and vascular
      development in mice.
AB  - The cardiovascular system develops during the early stages of embryogenesis, and
      differentiation of smooth muscle cells (SMCs) is essential for that process. SMC
      differentiation is critically regulated by transforming growth factor (TGF)
      beta/SMAD family member 3 (SMAD3) signaling, but other regulators may also play a
      role. For example, long noncoding RNAs (lncRNAs) regulate various cellular
      activities and events, such as proliferation, differentiation, and apoptosis.
      However, whether long noncoding RNAs also regulate SMC differentiation remains
      largely unknown. Here, using the murine cell line C3H10T1/2, we found that brain
      cytoplasmic RNA 1 (BC1) is an important regulator of SMC differentiation. BC1
      overexpression suppressed, whereas BC1 knockdown promoted, TGF-beta-induced SMC
      differentiation, as indicated by altered cell morphology and expression of
      multiple SMC markers, including smooth muscle alpha-actin (alphaSMA), calponin,
      and smooth muscle 22alpha (SM22alpha). BC1 appeared to block SMAD3 activity and
      inhibit SMC marker gene transcription. Mechanistically, BC1 bound to SMAD3 via
      RNA SMAD-binding elements (rSBEs) and thus impeded TGF-beta-induced SMAD3
      translocation to the nucleus. This prevented SMAD3 from binding to SBEs in SMC
      marker gene promoters, an essential event in SMC marker transcription. In vivo,
      BC1 overexpression in mouse embryos impaired vascular SMC differentiation,
      leading to structural defects in the artery wall, such as random breaks in the
      elastic lamina, abnormal collagen deposition on SM fibers, and disorganized
      extracellular matrix proteins in the media of the neonatal aorta. Our results
      suggest that BC1 is a suppressor of SMC differentiation during vascular
      development.

PMID- 29467229
TI  - MANAGEMENT OF ENDOCRINE DISEASE: Can we cure Cushing's disease? A personal view.
AB  - One of today's challenges in endocrinology is the treatment of Cushing's disease:
      Although pituitary surgery has the potential to 'cure' the patient and restore a
      completely normal pituitary adrenal axis, there are immediate failures and late
      recurrences that will ultimately require alternate therapeutic approaches. Their
      high number is in direct correlation with their serious limitations and they all
      appear to be 'default options'. This 'personal view' tries to shed some light on
      the inescapable difficulties of the current treatments of Cushing's disease and
      to provide some optimistic view for the future where the pituitary adenoma should
      be the 'reasonable obsession' of a successful therapeutist.

PMID- 29467227
TI  - Phosphorylation of CDC25C by AMP-activated protein kinase mediates a metabolic
      checkpoint during cell-cycle G2/M-phase transition.
AB  - From unicellular to multicellular organisms, cell-cycle progression is tightly
      coupled to biosynthetic and bioenergetic demands. Accumulating evidence has
      demonstrated the G1/S-phase transition as a key checkpoint where cells respond to
      their metabolic status and commit to replicating the genome. However, the
      mechanism underlying the coordination of metabolism and the G2/M-phase transition
      in mammalian cells remains unclear. Here, we show that the activation of AMP
      activated protein kinase (AMPK), a highly conserved cellular energy sensor,
      significantly delays mitosis entry. The cell-cycle G2/M-phase transition is
      controlled by mitotic cyclin-dependent kinase complex (CDC2-cyclin B), which is
      inactivated by WEE1 family protein kinases and activated by the opposing
      phosphatase CDC25C. AMPK directly phosphorylates CDC25C on serine 216, a well
      conserved inhibitory phosphorylation event, which has been shown to mediate DNA
      damage-induced G2-phase arrest. The acute induction of CDC25C or suppression of
      WEE1 partially restores mitosis entry in the context of AMPK activation. These
      findings suggest that AMPK-dependent phosphorylation of CDC25C orchestrates a
      metabolic checkpoint for the cell-cycle G2/M-phase transition.

PMID- 29467230
TI  - Unenhanced CT imaging is highly sensitive to exclude pheochromocytoma: a
      multicenter study.
AB  - BACKGROUND: A substantial proportion of all pheochromocytomas is currently
      detected during the evaluation of an adrenal incidentaloma. Recently, it has been
      suggested that biochemical testing to rule out pheochromocytoma is unnecessary in
      case of an adrenal incidentaloma with an unenhanced attenuation value <=10
      Hounsfield Units (HU) at computed tomography (CT). OBJECTIVES: We aimed to
      determine the sensitivity of the 10 HU threshold value to exclude a
      pheochromocytoma. METHODS: Retrospective multicenter study with systematic
      reassessment of preoperative unenhanced CT scans performed in patients in whom a
      histopathologically proven pheochromocytoma had been diagnosed. Unenhanced
      attenuation values were determined independently by two experienced radiologists.
      Sensitivity of the 10 HU threshold was calculated, and interobserver consistency
      was assessed using the intraclass correlation coefficient (ICC). RESULTS: 214
      patients were identified harboring a total number of 222 pheochromocytomas.
      Maximum tumor diameter was 51 (39-74) mm. The mean attenuation value within the
      region of interest was 36 +/- 10 HU. Only one pheochromocytoma demonstrated an
      attenuation value <=10 HU, resulting in a sensitivity of 99.6% (95% CI: 97.5
      99.9). ICC was 0.81 (95% CI: 0.75-0.86) with a standard error of measurement of
      7.3 HU between observers. CONCLUSION: The likelihood of a pheochromocytoma with
      an unenhanced attenuation value <=10 HU on CT is very low. The interobserver
      consistency in attenuation measurement is excellent. Our study supports the
      recommendation that in patients with an adrenal incidentaloma biochemical testing
      for ruling out pheochromocytoma is only indicated in adrenal tumors with an
      unenhanced attenuation value >10 HU.

PMID- 29467231
TI  - Diagnostic accuracy of computed tomography to identify adenomas among adrenal
      incidentalomas in an endocrinological population.
AB  - CONTEXT: The recent recommendations of the European Endocrine Society states that
      the performance of computed tomography (CT) to characterize 'true' adrenal
      incidentalomas (AIs) remains debatable. OBJECTIVE: To determine relevant
      thresholds for usual CT parameters for the diagnosis of benign tumors using
      robust reference standard among a large series of 'true' AIs recruited in an
      endocrinological setting. DESIGN: Retrospective study of 253 AIs in 233
      consecutive patients explored in a single university hospital: 183 adenomas, 33
      pheochromocytomas, 23 adrenocortical carcinomas, 5 other malignant tumors and 9
      other benign tumors. Reference standard was histopathology in 118 AIs, biological
      diagnosis of pheochromocytoma in 2 AIs and size stability after at least 1 year
      of follow-up in 133 AIs. METHODS: Sensitivity, specificity and positive and
      negative predictive values were estimated for various thresholds of size,
      unenhanced attenuation (UA), relative and absolute wash-out (RPW, APW) of
      contrast media. 197 scans were reviewed independently in a blinded fashion by two
      expert radiologists to assess inter-observer reproducibility of measurements.
      RESULTS: Criteria associated with a 100% positive predictive value for the
      diagnosis of benign AI were: a combination of size and UA: 30 mm and 20 HU or 40
      mm and 15 HU, respectively; RPW >53%; and APW >78%. Non-adenomatous AIs with
      rapid contrast wash-out were exclusively benign pseudocysts and
      pheochromocytomas, suggesting that classical thresholds of 60% and 40% for APW
      and RPW, respectively, can be safely used for patients with normal metanephrine
      values. Inter-observer reproducibility of all parameters was excellent (intra
      class correlation coefficients: 0.96-0.99). CONCLUSIONS: Our study, the largest
      conducted in AIs recruited in an endocrinological setting, suggests safe
      thresholds for quantitative CT parameters to avoid false diagnoses of benignity.

PMID- 29467232
TI  - Deletion in the uridine diphosphate glucuronyltransferase 2B17 gene is associated
      with delayed pubarche in healthy boys.
AB  - OBJECTIVE: Only a few genetic loci are known to be associated with male pubertal
      events. The ability of excreting testosterone (T) and other steroids in the urine
      depends on sulfation and glucuronidation. One of several essential glucuronidases
      is encoded by the UGT2B17 gene. In a preliminary report, we found that homozygous
      deletion of UGT2B17 in boys was associated with lower urinary excretion of T. We
      hypothesized that boys with a lower glucuronidation capacity may have altered
      androgen action and excretion affecting pubarche, as this represents a T
      dependent event. DESIGN, PARTICIPANTS AND MEASURES: 668 healthy boys (cross
      sectional) aged 6.1-21.9 years (COPENHAGEN puberty study conducted from 2005 to
      2006) were included. 65 of the boys where followed longitudinally every 6 months.
      Participants were genotyped for UGT2B17 copy number variation (CNV). Clinical
      pubertal staging including orchidometry, anthropometry and serum reproductive
      hormone levels. RESULTS: 59 of the 668 boys (8.8%) presented with a homozygous
      deletion of UGT2B17 (del/del). These boys experienced pubarche at a mean age of
      12.73 years (12.00-13.46) vs 12.40 years (12.11-12.68) in boys heterozygous for
      deletion of UGT2B17 (del/ins) vs 12.06 years (11.79-12.33) in boys with the wild
      type genotype (ins/ins) (P = 0.029, corrected for BMI z-score). The effect
      accounted for 0.34 years delay per allele (95% CI: 0.03-0.64). A comparable trend
      was observed for onset of testicular enlargement >3 mL but did not reach
      significance. CONCLUSION: CNV of UGT2B17 is a factor contributing to the timing
      of male pubarche.

PMID- 29467234
TI  - Correction: CIP2A acts as a scaffold for CEP192-mediated microtubule organizing
      center assembly by recruiting Plk1 and aurora A during meiotic maturation
      (doi:10.1242/dev.158584).

PMID- 29467233
TI  - Validating upstream regulators of Yorkie activity in Hippo signaling through
      scalloped-based genetic epistasis.
AB  - Genetic studies in Drosophila have been instrumental in characterizing the Hippo
      pathway, which converges on the co-activator Yorkie to regulate target gene
      transcription. A routinely used strategy to interrogate upstream regulators of
      Yorkie involves the examination of selected Hippo target genes upon loss or gain
      of function of a suspected pathway regulator. A caveat with this strategy is that
      aberrant expression of a given Hippo target per se does not distinguish whether
      it is caused by changes in Yorkie or Yorkie-independent inputs converging on the
      same target gene. Building on previous findings that the DNA-binding
      transcription factor Scalloped mediates both Yorkie overexpression and loss-of
      function phenotypes yet is itself dispensable for normal eye development, we
      describe a simple strategy to distinguish these possibilities by analyzing double
      mutant clones of scalloped and a suspected Yorkie regulator. We provide proof of
      principle that this strategy can be used effectively to validate canonical Yorkie
      regulators and to exclude proteins that impact target expression independent of
      Yorkie. The described methodology and reagents should facilitate efforts to
      assess the expanding repertoire of proteins implicated in regulation of Yorkie
      activity.

PMID- 29467235
TI  - Explanation and elaboration of the Standards for UNiversal reporting of patient
      Decision Aid Evaluations (SUNDAE) guidelines: examples of reporting SUNDAE items
      from patient decision aid evaluation literature.
AB  - This Explanation and Elaboration (E&E) article expands on the 26 items in the
      Standards for UNiversal reporting of Decision Aid Evaluations guidelines. The E&E
      provides a rationale for each item and includes examples for how each item has
      been reported in published papers evaluating patient decision aids. The E&E
      focuses on items key to reporting studies evaluating patient decision aids and is
      intended to be illustrative rather than restrictive. Authors and reviewers may
      wish to use the E&E broadly to inform structuring of patient decision aid
      evaluation reports, or use it as a reference to obtain details about how to
      report individual checklist items.

PMID- 29467236
TI  - Hematopoietic stem cells from induced pluripotent stem cells - considering the
      role of microRNA as a cell differentiation regulator.
AB  - Although hematopoietic stem cell (HSC) therapy for hematological diseases can
      lead to a good outcome from the clinical point of view, the limited number of
      ideal donors, the comorbidity of patients and the increasing number of elderly
      patients may limit the application of this therapy. HSCs can be generated from
      induced pluripotent stem cells (iPSCs), which requires the understanding of the
      bone marrow and liver niches components and function in vivo iPSCs have been
      extensively applied in several studies involving disease models, drug screening
      and cellular replacement therapies. However, the somatic reprogramming by
      transcription factors is a low-efficiency process. Moreover, the reprogramming
      process is also regulated by microRNAs (miRNAs), which modulate the expression of
      the transcription factors OCT-4 (also known as POU5F1), SOX-2, KLF-4 and MYC,
      leading somatic cells to a pluripotent state. In this Review, we present an
      overview of the challenges of cell reprogramming protocols with regard to HSC
      generation from iPSCs, and highlight the potential role of miRNAs in cell
      reprogramming and in the differentiation of induced pluripotent stem cells.

PMID- 29467237
TI  - Implications of Recent Clinical Trials and Hypertension Guidelines on Stroke and
      Future Cerebrovascular Research.

PMID- 29467238
TI  - Ethanol Reversal of Oxycodone Tolerance in Dorsal Root Ganglia Neurons.
AB  - Oxycodone is a semisynthetic opioid compound that is widely prescribed, used, and
      abused today, and has a well-established role in shaping the current opioid
      epidemic. Previously, we have shown that tolerance develops to the
      antinociceptive and respiratory depressive effects of oxycodone in mice, and that
      a moderate dose of acute ethanol or a protein kinase C (PKC) inhibitor reversed
      that tolerance. To investigate further if tolerance was occurring through
      neuronal mechanisms, our aims for this study were to assess the effects of acute
      and prolonged oxycodone in isolated dorsal root ganglia (DRG) neurons and to
      determine if this tolerance was reversed by either ethanol or a PKC inhibitor. We
      found that an acute exposure to 3 MUM oxycodone reduced neuronal excitability, as
      measured by increased threshold potentials and reduced action potential
      amplitude, without eliciting measurable changes in resting membrane potential.
      Exposure to 10 MUM oxycodone for 18-24 hours prevented oxycodone's effect on
      neuronal excitability, indicative of tolerance development. The development of
      opioid tolerance was mitigated in DRG neurons from beta-arrestin 2 knockout mice.
      Oxycodone tolerance was reversed in isolated DRG neurons by the acute application
      of either ethanol (20 mM) or the PKC inhibitor, bisindolylmaleimide XI
      hydrochloride (Bis XI), when a challenge of 3 uM oxycodone significantly reduced
      neuronal excitability following prolonged exposure. Through these studies, we
      concluded that oxycodone acutely reduced neuronal excitability, tolerance
      developed to this effect, and reversal of that tolerance occurred at the level of
      a single neuron, suggesting that reversal of oxycodone tolerance by either
      ethanol or Bis XI involves cellular mechanisms.

PMID- 29467239
TI  - Frequency and consequence of the recurrent YY1 p.T372R mutation in sporadic
      insulinomas.

PMID- 29467241
TI  - Polar cell fate stimulates Wolbachia intracellular growth.
AB  - Bacteria are crucial partners in the development and evolution of vertebrates and
      invertebrates. A large fraction of insects harbor Wolbachia, bacterial
      endosymbionts that manipulate host reproduction to favor their spreading. Because
      they are maternally inherited, Wolbachia are under selective pressure to reach
      the female germline and infect the offspring. However, Wolbachia infection is not
      limited to the germline. Somatic cell types, including stem cell niches, have
      higher Wolbachia loads compared with the surrounding tissue. Here, we show a
      novel Wolbachia tropism to polar cells (PCs), specialized somatic cells in the
      Drosophila ovary. During oogenesis, all stages of PC development are easily
      visualized, facilitating the investigation of the kinetics of Wolbachia
      intracellular growth. Wolbachia accumulation is triggered by particular events of
      PC morphogenesis, including differentiation from progenitors and between stages 8
      and 9 of oogenesis. Moreover, induction of ectopic PC fate is sufficient to
      promote Wolbachia accumulation. We found that Wolbachia PC tropism is
      evolutionarily conserved across most Drosophila species, but not in Culex
      mosquitos. These findings highlight the coordination of endosymbiont tropism with
      host development and cell differentiation.

PMID- 29467240
TI  - Identification, isolation and characterization of human LGR5-positive colon
      adenoma cells.
AB  - The intestine is maintained by stem cells located at the base of crypts and
      distinguished by the expression of LGR5. Genetically engineered mouse models have
      provided a wealth of information about intestinal stem cells, whereas less is
      known about human intestinal stem cells owing to difficulty detecting and
      isolating these cells. We established an organoid repository from patient-derived
      adenomas, adenocarcinomas and normal colon, which we analyzed for variants in 71
      colorectal cancer (CRC)-associated genes. Normal and neoplastic colon tissue
      organoids were analyzed by immunohistochemistry and fluorescent-activated cell
      sorting for LGR5. LGR5-positive cells were isolated from four adenoma organoid
      lines and were subjected to RNA sequencing. We found that LGR5 expression in the
      epithelium and stroma was associated with tumor stage, and by integrating
      functional experiments with LGR5-sorted cell RNA sequencing data from adenoma and
      normal organoids, we found correlations between LGR5 and CRC-specific genes,
      including dickkopf WNT signaling pathway inhibitor 4 (DKK4) and SPARC-related
      modular calcium binding 2 (SMOC2). Collectively, this work provides resources,
      methods and new markers to isolate and study stem cells in human tissue
      homeostasis and carcinogenesis.

PMID- 29467243
TI  - Hormonal control of growth in the wing imaginal disks of Junonia coenia: the
      relative contributions of insulin and ecdysone.
AB  - The wing imaginal disks of Lepidoptera can be grown in tissue culture, but
      require both insulin and ecdysone to grow normally. Here, we investigate the
      contributions the two hormones make to growth. Ecdysone is required to maintain
      mitoses, whereas in the presence of insulin alone mitoses stop. Both ecdysone and
      insulin stimulate protein synthesis, but only ecdysone stimulates DNA synthesis.
      Insulin stimulates primarily cytoplasmic growth and an increase in cell size,
      whereas ecdysone, by virtue of its stimulation of DNA synthesis and mitosis,
      stimulates growth by an increase in cell number. Although both hormones stimulate
      protein synthesis, they do so in different spatial patterns. Both hormones
      stimulate protein synthesis in the inter-vein regions, but ecdysone stimulates
      synthesis more strongly in the veins and in the margin of the wing disk. We
      propose that the balance of insulin and ecdysone signaling must be regulated to
      maintain normal growth, and when growth appears to be due primarily to an
      increase in cell number, or an increase in cell size, this may indicate growth
      occurred under conditions that favored a stronger role for ecdysone, or insulin,
      respectively.

PMID- 29467242
TI  - Prothoracicotropic hormone modulates environmental adaptive plasticity through
      the control of developmental timing.
AB  - Adult size and fitness are controlled by a combination of genetics and
      environmental cues. In Drosophila, growth is confined to the larval phase and
      final body size is impacted by the duration of this phase, which is under
      neuroendocrine control. The neuropeptide prothoracicotropic hormone (PTTH) has
      been proposed to play a central role in controlling the length of the larval
      phase through regulation of ecdysone production, a steroid hormone that initiates
      larval molting and metamorphosis. Here, we test this by examining the
      consequences of null mutations in the Ptth gene for Drosophila development. Loss
      of Ptth causes several developmental defects, including a delay in developmental
      timing, increase in critical weight, loss of coordination between body and
      imaginal disc growth, and reduced adult survival in suboptimal environmental
      conditions such as nutritional deprivation or high population density. These
      defects are caused by a decrease in ecdysone production associated with altered
      transcription of ecdysone biosynthetic genes. Therefore, the PTTH signal
      contributes to coordination between environmental cues and the developmental
      program to ensure individual fitness and survival.

PMID- 29467244
TI  - Precise spatial restriction of BMP signaling in developing joints is perturbed
      upon loss of embryo movement.
AB  - Dynamic mechanical loading of synovial joints is necessary for normal joint
      development, as evidenced in certain clinical conditions, congenital disorders
      and animal models where dynamic muscle contractions are reduced or absent.
      Although the importance of mechanical forces on joint development is unequivocal,
      little is known about the molecular mechanisms involved. Here, using chick and
      mouse embryos, we observed that molecular changes in expression of multiple genes
      analyzed in the absence of mechanical stimulation are consistent across species.
      Our results suggest that abnormal joint development in immobilized embryos
      involves inappropriate regulation of Wnt and BMP signaling during definition of
      the emerging joint territories, i.e. reduced beta-catenin activation and
      concomitant upregulation of pSMAD1/5/8 signaling. Moreover, dynamic mechanical
      loading of the developing knee joint activates Smurf1 expression; our data
      suggest that Smurf1 insulates the joint region from pSMAD1/5/8 signaling and is
      essential for maintenance of joint progenitor cell fate.

PMID- 29467245
TI  - Lineage- and stage-specific expressed CYCD7;1 coordinates the single symmetric
      division that creates stomatal guard cells.
AB  - Plants, with cells fixed in place by rigid walls, often utilize spatial and
      temporally distinct cell division programs to organize and maintain organs. This
      leads to the question of how developmental regulators interact with the cell
      cycle machinery to link cell division events with particular developmental
      trajectories. In Arabidopsis leaves, the development of stomata, two-celled
      epidermal valves that mediate plant-atmosphere gas exchange, relies on a series
      of oriented stem cell-like asymmetric divisions followed by a single symmetric
      division. The stomatal lineage is embedded in a tissue in which other cells
      transition from proliferation to postmitotic differentiation earlier,
      necessitating stomatal lineage-specific factors to prolong competence to divide.
      We show that the D-type cyclin, CYCD7;1, is specifically expressed just prior to
      the symmetric guard cell-forming division, and that it is limiting for this
      division. Further, we find that CYCD7;1 is capable of promoting divisions in
      multiple contexts, likely through RBR1-dependent promotion of the G1/S
      transition, but that CYCD7;1 is regulated at the transcriptional level by cell
      type-specific transcription factors that confine its expression to the
      appropriate developmental window.

PMID- 29467246
TI  - The transcriptome of early chicken embryos reveals signaling pathways governing
      rapid asymmetric cellularization and lineage segregation.
AB  - The phylogenomics and comparative functional genomics of avian species were
      investigated in the Bird 10,000 Genomes (B10K) project because of the important
      evolutionary position of birds and their value as a research model. However, the
      systematic profiling of transcriptional changes prior to oviposition has not been
      investigated in avian species because of the practical difficulties in obtaining
      pre-oviposited eggs. In this study, a total of 137 pre-oviposited embryos were
      collected from hen ovaries and oviducts and subjected to RNA-sequencing analyses.
      Two waves of chicken zygotic genome activation (ZGA) were observed. Functionally
      distinct developmental programs involving Notch, MAPK, Wnt and TGFbeta signaling
      were separately detected during cleavage and area pellucida formation.
      Furthermore, the early stages of chicken development were compared with the human
      and mouse counterparts, highlighting chicken-specific signaling pathways and
      gradually analogous gene expression via ZGA. These findings provide a genome-wide
      understanding of avian embryogenesis and comparisons among amniotes.

PMID- 29467247
TI  - Fat body glycogen serves as a metabolic safeguard for the maintenance of sugar
      levels in Drosophila.
AB  - Adapting to changes in food availability is a central challenge for survival.
      Glucose is an important resource for energy production, and therefore many
      organisms synthesize and retain sugar storage molecules. In insects, glucose is
      stored in two different forms: the disaccharide trehalose and the branched
      polymer glycogen. Glycogen is synthesized and stored in several tissues,
      including in muscle and the fat body. Despite the major role of the fat body as a
      center for energy metabolism, the importance of its glycogen content remains
      unclear. Here, we show that glycogen metabolism is regulated in a tissue-specific
      manner under starvation conditions in the fruit fly Drosophila The mobilization
      of fat body glycogen in larvae is independent of Adipokinetic hormone (Akh, the
      glucagon homolog) but is regulated by sugar availability in a tissue-autonomous
      manner. Fat body glycogen plays a crucial role in the maintenance of circulating
      sugars, including trehalose, under fasting conditions. These results demonstrate
      the importance of fat body glycogen as a metabolic safeguard in Drosophila.

PMID- 29467249
TI  - RNA tales - how embryos read and discard messages from mom.
AB  - Following fertilization, embryos develop for a substantial amount of time with a
      transcriptionally silent genome. Thus, early development is maternally
      programmed, as it solely relies on RNAs and proteins that are provided by the
      female gamete. However, these maternal instructions are not sufficient to support
      later steps of embryogenesis and are therefore gradually replaced by novel
      products synthesized from the zygotic genome. This switch in the origin of
      molecular players that drive early development is known as the maternal-to
      zygotic transition (MZT). MZT is a universal phenomenon among all metazoans and
      comprises two interconnected processes: maternal mRNA degradation and the
      transcriptional awakening of the zygotic genome. The recent adaptation of high
      throughput methods for use in embryos has deepened our knowledge of the molecular
      principles underlying MZT. These mechanisms comprise conserved strategies for RNA
      regulation that operate in many well-studied cellular contexts but that have
      adapted differently to early development. In this Review, we will discuss
      advances in our understanding of post-transcriptional regulatory pathways that
      drive maternal mRNA clearance during MZT, with an emphasis on recent data in
      zebrafish embryos on codon-mediated mRNA decay, the contributions of microRNAs
      (miRNAs) and RNA-binding proteins to this process, and the roles of RNA
      modifications in the stability control of maternal mRNAs.

PMID- 29467248
TI  - alpha-Catenin-dependent cytoskeletal tension controls Yap activity in the heart.
AB  - Shortly after birth, muscle cells of the mammalian heart lose their ability to
      divide. At the same time, the N-cadherin/catenin cell adhesion complex
      accumulates at the cell termini, creating a specialized type of cell-cell contact
      called the intercalated disc (ICD). To investigate the relationship between ICD
      maturation and proliferation, alphaE-catenin (Ctnna1) and alphaT-catenin (Ctnna3)
      genes were deleted to generate cardiac-specific alpha-catenin double knockout
      (DKO) mice. DKO mice exhibited aberrant N-cadherin expression, mislocalized
      actomyosin activity and increased cardiomyocyte proliferation that was dependent
      on Yap activity. To assess effects on tension, cardiomyocytes were cultured on
      deformable polyacrylamide hydrogels of varying stiffness. When grown on a stiff
      substrate, DKO cardiomyocytes exhibited increased cell spreading, nuclear Yap and
      proliferation. A low dose of either a myosin or RhoA inhibitor was sufficient to
      block Yap accumulation in the nucleus. Finally, activation of RhoA was sufficient
      to increase nuclear Yap in wild-type cardiomyocytes. These data demonstrate that
      alpha-catenins regulate ICD maturation and actomyosin contractility, which, in
      turn, control Yap subcellular localization, thus providing an explanation for the
      loss of proliferative capacity in the newborn mammalian heart.

PMID- 29467250
TI  - Different contributions of nonmuscle myosin IIA and IIB to the organization of
      stress fiber subtypes in fibroblasts.
AB  - We demonstrated that myosin IIA and IIB are essential for the formation of
      transverse arcs and ventral stress fibers, respectively. Furthermore, we
      illustrated the roles of both isoforms in lamellar flattening and also raised the
      possibility that actin filaments in ventral stress fibers are in a stretched
      conformation.

PMID- 29467251
TI  - The IDA3 adapter, required for intraflagellar transport of I1 dynein, is
      regulated by ciliary length.
AB  - We determined how the ciliary motor I1 dynein is transported. A specialized
      adapter, IDA3, facilitates I1 dynein attachment to the ciliary transporter called
      intraflagellar transport (IFT). Loading of IDA3 and I1 dynein on IFT is regulated
      by ciliary length.

PMID- 29467252
TI  - Yeast Aim21/Tda2 both regulates free actin by reducing barbed end assembly and
      forms a complex with Cap1/Cap2 to balance actin assembly between patches and
      cables.
AB  - Yeast Aim21 is recruited by the SH3-containing proteins Bbc1 and Abp1 to patches
      and, with Tda2, reduces barbed end assembly to balance the distribution of actin
      between patches and cables. Aim21/Tda2 also interacts with Cap1/Cap2, revealing a
      complex interplay between actin assembly regulators.

PMID- 29467253
TI  - Membrane detachment is not essential for COG complex function.
AB  - COG is a multisubunit vesicle tethering complex in the Golgi. We demonstrate that
      both COG subcomplexes can be permanently attached to Golgi membranes and that
      major COG functions do not require cycling between the membrane and cytosol.

PMID- 29467254
TI  - BDNF activates an NFI-dependent neurodevelopmental timing program by sequestering
      NFATc4.
AB  - We show that BDNF regulates the timing of neurodevelopment via a novel mechanism
      of extranuclear sequestration of NFATc4 in Golgi. This leads to accelerated
      derepression of an NFI temporal occupancy gene program in cerebellar granule
      cells that includes Bdnf itself, revealing an autoregulatory loop within the
      program driven by BDNF and NFATc4.

PMID- 29467255
TI  - Altered translation initiation of Gja1 limits gap junction formation during
      epithelial-mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) is activated during development, wound
      healing, and pathologies including fibrosis and cancer metastasis. Hallmarks of
      EMT are remodeling of intercellular junctions and adhesion proteins, including
      gap junctions. The GJA1 mRNA transcript encoding the gap junction protein
      connexin43 (Cx43) has been demonstrated to undergo internal translation
      initiation, yielding truncated isoforms that modulate gap junctions. The
      PI3K/Akt/mTOR pathway is central to translation regulation and is activated
      during EMT, leading us to hypothesize that altered translation initiation would
      contribute to gap junction loss. Using TGF-beta-induced EMT as a model, we find
      reductions in Cx43 gap junctions despite increased transcription and
      stabilization of Cx43 protein. Biochemical experiments reveal suppression of the
      internally translated Cx43 isoform, GJA1-20k in a Smad3 and ERK-dependent manner.
      Ectopic expression of GJA1-20k does not halt EMT, but is sufficient to rescue gap
      junction formation. GJA1-20k localizes to the Golgi apparatus, and using super
      resolution localization we find retention of GJA1-43k at the Golgi in mesenchymal
      cells lacking GJA1-20k. NativePAGE reveals that levels of GJA1-20k regulate GJA1
      43k hexamer oligomerization, a limiting step in Cx43 trafficking. These findings
      reveal alterations in translation initiation as an unexplored mechanism by which
      the cell regulates Cx43 gap junction formation during EMT.

PMID- 29467256
TI  - Commonly used trafficking blocks disrupt ARF1 activation and the localization and
      function of specific Golgi proteins.
AB  - Cold temperature blocks used to synchronize protein trafficking inhibit GBF1
      function, leading to a decrease in ARF1-GTP levels and mislocalization of the
      ARF1 effector golgin-160. Several other, but not all, Golgi proteins including
      ARL1 also mislocalize. ARF1 activity and golgin-160 localization require more
      than 30 min to recover from these blocks.

PMID- 29467257
TI  - Product diffusion through on-demand information-seeking behaviour.
AB  - Most models of product adoption predict S-shaped adoption curves. Here we report
      results from two country-scale experiments in which we find linear adoption
      curves. We show evidence that the observed linear pattern is the result of active
      information-seeking behaviour: individuals actively pulling information from
      several central sources facilitated by modern Internet searches. Thus, a constant
      baseline rate of interest sustains product diffusion, resulting in a linear
      diffusion process instead of the S-shaped curve of adoption predicted by many
      diffusion models. The main experiment seeded 70 000 (48 000 in Experiment 2)
      unique voucher codes for the same product with randomly sampled nodes in a social
      network of approximately 43 million individuals with about 567 million ties. We
      find that the experiment reached over 800 000 individuals with 80% of adopters
      adopting the same product-a winner-take-all dynamic consistent with search engine
      driven rankings that would not have emerged had the products spread only through
      a network of social contacts. We provide evidence for (and characterization of)
      this diffusion process driven by active information-seeking behaviour through
      analyses investigating (a) patterns of geographical spreading; (b) the branching
      process; and (c) diffusion heterogeneity. Using data on adopters' geolocation we
      show that social spreading is highly localized, while on-demand diffusion is
      geographically independent. We also show that cascades started by individuals who
      actively pull information from central sources are more effective at spreading
      the product among their peers.

PMID- 29467258
TI  - Tendon healing affects the multiscale mechanical, structural and compositional
      response of tendon to quasi-static tensile loading.
AB  - Tendon experiences a variety of multiscale changes to its extracellular matrix
      during mechanical loading at the fascicle, fibre and fibril levels. For example,
      tensile loading of tendon increases its stiffness, with organization of collagen
      fibres, and increases cell strain in the direction of loading. Although applied
      macroscale strains correlate to cell and nuclear strains in uninjured tendon, the
      multiscale response during tendon healing remains unknown and may affect cell
      mechanosensing and response. Therefore, this study evaluated multiscale structure
      function mechanisms in response to quasi-static tensile loading in uninjured and
      healing tendons. We found that tendon healing affected the macroscale mechanical
      and structural response to mechanical loading, evidenced by decreases in strain
      stiffening and collagen fibre realignment. At the micro- and nanoscales, healing
      resulted in increased collagen fibre disorganization, nuclear disorganization,
      decreased change in nuclear aspect ratio with loading, and decreased indentation
      modulus compared to uninjured tendons. Taken together, this work supports a new
      concept of nuclear strain transfer attenuation during tendon healing and
      identifies several multiscale properties that may contribute. Our work also
      provides benchmarks for the biomechanical microenvironments that tendon cells may
      experience following cell delivery therapies.

PMID- 29467259
TI  - Structural origins of coloration in the spider Phoroncidia rubroargentea Berland,
      1913 (Araneae: Theridiidae) from Madagascar.
AB  - This study investigates the structural basis for the red, silver and black
      coloration of the theridiid spider, Phoroncidia rubroargentea (Berland, 1913)
      from Madagascar. Specimens of this species can retain their colour after storage
      in ethanol for decades, whereas most other brightly pigmented spider specimens
      fade under identical preservation conditions. Using correlative optical,
      structural and chemical analysis, we identify the colour-generating structural
      elements and characterize their optical properties. The prominent silvery
      appearance of the spider's abdomen results from regularly arranged guanine
      microplatelets, similar to those found in other spiders and fish. The
      microplatelets are composed of a doublet structure twinned about the [[Formula:
      see text]] axis, as suggested by electron diffraction. The red coloration
      originates from chambered microspheres (approx. 1 um in diameter), which contain
      structured fluorescent material. Co-localization of the red microparticles on top
      of the reflective guanine microplatelets appears to enhance the red coloration.
      The spider's thick cuticular layer, which encases its abdomen, varies in its
      optical properties, being transparent in regions where only guanine reflectors
      are present, and tanned, exhibiting light absorption where the red microspheres
      are found. Moreover, colour degradation in some preserved spider specimens that
      had suffered damage to the cuticular layer suggests that this region of the
      exoskeleton may play an important role in the stabilization of the red
      coloration.

PMID- 29467260
TI  - Clownfishes evolution below and above the species level.
AB  - The difference between rapid morphological evolutionary changes observed in
      populations and the long periods of stasis detected in the fossil record has
      raised a decade-long debate about the exact role played by intraspecific
      mechanisms at the interspecific level. Although they represent different scales
      of the same evolutionary process, micro- and macroevolution are rarely studied
      together and few empirical studies have compared the rates of evolution and the
      selective pressures between both scales. Here, we analyse morphological, genetic
      and ecological traits in clownfishes at different evolutionary scales and
      demonstrate that the tempo of molecular and morphological evolution at the
      species level can be, to some extent, predicted from parameters estimated below
      the species level, such as the effective population size or the rate of evolution
      within populations. We also show that similar codons in the gene of the rhodopsin
      RH1, a light-sensitive receptor protein, are under positive selection at the
      intra and interspecific scales, suggesting that similar selective pressures are
      acting at both levels.

PMID- 29467261
TI  - Estimating encounter rates as the first step of sexual selection in the lizard
      Anolis sagrei.
AB  - How individuals move through their environment dictates which other individuals
      they encounter, determining their social and reproductive interactions and the
      extent to which they experience sexual selection. Specifically, females rarely
      have the option of mating with all males in a population-they can only choose
      among the males they encounter. Further, quantifying phenotypic differences
      between the males that females encounter and those that sire females' offspring
      lends insight into how social and reproductive interactions shape male
      phenotypes. We used an explicitly spatio-temporal Markov chain model to estimate
      the number of potential mates of Anolis sagrei lizards from their movement
      behaviour, and used genetic paternity assignments to quantify sexual selection on
      males. Females frequently encountered and mated with multiple males, offering
      ample opportunity for female mate choice. Sexual selection favoured males that
      were bigger and moved over larger areas, though the effect of body size cannot be
      disentangled from last-male precedence. Our approach corroborates some patterns
      of sexual selection previously hypothesized in anoles based on describing them as
      territorial, whereas other results, including female multiple mating itself, are
      at odds with territorial polygyny, offering insight into discrepancies in other
      taxa between behavioural and genetic descriptions of mating systems.

PMID- 29467262
TI  - Flight range, fuel load and the impact of climate change on the journeys of
      migrant birds.
AB  - Climate change is predicted to increase migration distances for many migratory
      species, but the physiological and temporal implications of longer migratory
      journeys have not been explored. Here, we combine information about species'
      flight range potential and migratory refuelling requirements to simulate the
      number of stopovers required and the duration of current migratory journeys for
      77 bird species breeding in Europe. Using tracking data, we show that our
      estimates accord with recorded journey times and stopovers for most species. We
      then combine projections of altered migratory distances under climate change with
      models of avian flight to predict future migratory journeys. We find that 37% of
      migratory journeys undertaken by long-distance migrants will necessitate an
      additional stopover in future. These greater distances and the increased number
      of stops will substantially increase overall journey durations of many long
      distance migratory species, a factor not currently considered in climate impact
      studies.

PMID- 29467263
TI  - Mutation accumulation is still potentially problematic, despite declining
      paternal age: a comment on Arslan et al. (2017).

PMID- 29467264
TI  - Macroevolutionary patterning of woodpecker drums reveals how sexual selection
      elaborates signals under constraint.
AB  - Sexual selection drives elaboration in animal displays used for competition and
      courtship, but this process is opposed by morphological constraints on signal
      design. How do interactions between selection and constraint shape display
      evolution? One possibility is that sexual selection continues exaggeration under
      constraint by operating differentially on each signal component in complex,
      modular displays. This is seldom studied on a phylogenetic scale, but we address
      the issue herein by studying macroevolutionary patterning of woodpecker drum
      displays. These territorial displays are produced when an individual rapidly hits
      its bill on a hard surface, and drums vary across species in the number of beats
      included (length) and the rate of drumbeat production (speed). We report that
      species body size limits drum speed, but not drum length. As a result of this
      biomechanical constraint, there is less standing variation in speed than length.
      We also uncover a positive relationship between sexual size dimorphism and the
      unconstrained trait (length), but with no effect on speed. This suggests that
      when morphology limits the exaggeration of one component, sexual selection
      instead exaggerates the unconstrained trait. Modular displays therefore provide
      the basis for selection to find novel routes to phenotypic elaboration after
      previous ones are closed.

PMID- 29467265
TI  - apterous A specifies dorsal wing patterns and sexual traits in butterflies.
AB  - Butterflies have evolved different colour patterns on their dorsal and ventral
      wing surfaces to serve different signalling functions, yet the developmental
      mechanisms controlling surface-specific patterning are still unknown. Here, we
      mutate both copies of the transcription factor apterous in Bicyclus anynana
      butterflies using CRISPR/Cas9 and show that apterous A, expressed dorsally,
      functions both as a repressor and modifier of ventral wing colour patterns, as
      well as a promoter of dorsal sexual ornaments in males. We propose that the
      surface-specific diversification of wing patterns in butterflies proceeded via
      the co-option of apterous A or its downstream effectors into various gene
      regulatory networks involved in the differentiation of discrete wing traits.
      Further, interactions between apterous and sex-specific factors such as doublesex
      may have contributed to the origin of sexually dimorphic surface-specific
      patterns. Finally, we discuss the evolution of eyespot number diversity in the
      family Nymphalidae within the context of developmental constraints due to
      apterous regulation.

PMID- 29467266
TI  - Oldest known multituberculate stapes suggests an asymmetric bicrural pattern as
      ancestral for Multituberculata.
AB  - Middle ear ossicles (malleus, incus, stapes) are known for few multituberculate
      taxa, and three different stapedial morphotypes have been suggested: (i) slender,
      columelliform and microperforate, (ii) robust and rod-like, and (iii) bicrural.
      Reinvestigation of Upper Jurassic (Kimmeridgian) mammalian petrosals from the
      Guimarota coal mine in central Portugal (Western Europe) revealed an asymmetric
      bicrural stapes (ABS) in the paulchoffatiid Pseudobolodon oreas The middle ear
      ossicles displaced inside the osseous vestibule were detected by a uCT analysis.
      The Kimmeridgian age of the Guimarota stapes exceeds the stapes from the Early
      Cretaceous (Barremian) of Asia (about 122-124 Ma) by approximately 30 Myr, and is
      only slightly younger than the stapes of the recently described Oxfordian
      euharamiyidan Arboroharamiya allinhopsoni The Guimarota stapes indicates that the
      stapes of Lambdopsalis, described as columelliform and microperforate (small
      stapedial foramen), does not represent a general condition for multituberculates.
      The stapes of Pseudobolodon is bicrural, the anterior crus sits centrally on the
      oval footplate, and the stapedial head is simple and smaller than the footplate.
      We hypothesize that the ABS evolved from the symmetric bicrural stapes (SBS) of
      non-mammaliaform cynodonts. The ABS appears to be the ancestral morphotype of the
      mammalian SBS, and the mammalian columelliform imperforate stapes.

PMID- 29467267
TI  - Pattern and process in hominin brain size evolution are scale-dependent.
AB  - A large brain is a defining feature of modern humans, yet there is no consensus
      regarding the patterns, rates and processes involved in hominin brain size
      evolution. We use a reliable proxy for brain size in fossils, endocranial volume
      (ECV), to better understand how brain size evolved at both clade- and lineage
      level scales. For the hominin clade overall, the dominant signal is consistent
      with a gradual increase in brain size. This gradual trend appears to have been
      generated primarily by processes operating within hypothesized lineages-64% or
      88% depending on whether one uses a more or less speciose taxonomy, respectively.
      These processes were supplemented by the appearance in the fossil record of
      larger-brained Homo species and the subsequent disappearance of smaller-brained
      Australopithecus and Paranthropus taxa. When the estimated rate of within-lineage
      ECV increase is compared to an exponential model that operationalizes generation
      scale evolutionary processes, it suggests that the observed data were the result
      of episodes of directional selection interspersed with periods of stasis and/or
      drift; all of this occurs on too fine a timescale to be resolved by the current
      human fossil record, thus producing apparent gradual trends within lineages. Our
      findings provide a quantitative basis for developing and testing scale-explicit
      hypotheses about the factors that led brain size to increase during hominin
      evolution.

PMID- 29467268
TI  - Relaxed selection and mutation accumulation are best studied empirically: reply
      to Woodley of Menie et al.

PMID- 29467269
TI  - Polygamy or subdioecy? The impact of diallelic self-incompatibility on the sexual
      system in Fraxinus excelsior (Oleaceae).
AB  - How flowering plants have recurrently evolved from hermaphroditism to separate
      sexes (dioecy) is a central question in evolutionary biology. Here, we
      investigate whether diallelic self-incompatibility (DSI) is associated with
      sexual specialization in the polygamous common ash (Fraxinus excelsior), which
      would ultimately facilitate the evolution towards dioecy. Using interspecific
      crosses, we provide evidence of strong relationships between the DSI system and
      sexual phenotype. The reproductive system in F. excelsior that was previously
      viewed as polygamy (co-occurrence of unisexuals and hermaphrodites with varying
      degrees of allocation to the male and female functions) and thus appears to
      actually behave as a subdioecious system. Hermaphrodites and females belong to
      one SI group and functionally reproduce as females, whereas males and male-biased
      hermaphrodites belong to the other SI group and are functionally males. Our
      results offer an alternative mechanism for the evolution of sexual specialization
      in flowering plants.

PMID- 29467270
TI  - Correction to 'Species delimitation for the molecular taxonomy and ecology of the
      widely distributed microbial eukaryote genus Euplotes'.

PMID- 29467271
TI  - Correction to 'Imitation of novel conspecific and human speech sounds in the
      killer whale (Orcinus orca)'.

PMID- 29467272
TI  - Cyclic Mechanical Stretch Up-regulates Hepatoma-Derived Growth Factor Expression
      in Cultured Rat Aortic Smooth Muscle Cells.
AB  - Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth
      muscle cells (SMCs) during embryogenesis and injury repair of vessel walls.
      Whether mechanical stimuli modulate HDGF expression remains unknown. This study
      aimed at investigating whether cyclic mechanical stretch plays a regulatory role
      in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC
      cell line was grown on a silicone-based elastomer chamber with extracellular
      matrix coatings (either type I collagen or fibronectin) and received cyclic and
      uni-axial mechanical stretches with 10% deformation at frequency 1 Hz.
      Morphological observation showed that fibronectin coating provided better cell
      adhesion and spreading and that consecutive 6 hours of cyclic mechanical stretch
      remarkably induced reorientation and realignment of SMCs. Western blotting
      detection demonstrated that continuous mechanical stimuli elicited up-regulation
      of HDGF and PCNA, a cell proliferative marker. Signal kinetic profiling study
      indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK
      and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of
      PI3K activity suppressed the stretch-induced TNF-a, whereas RhoA/ROCK inhibition
      significantly blunted the IL-6 production and HDGF over-expression. Moreover,
      siRNA-mediated HDGF gene silencing significantly suppressed constitutive
      expression of IL-6, but not TNF-alpha, in SMCs. These findings support the role
      of HDGF in maintaining vascular expression of IL-6, which has been regarded a
      crucial regenerative factor for acute vascular injury. In conclusion, cyclic
      mechanical stretch may maintain constitutive expression of HDGF in vascular walls
      and be regarded an important biophysical regulator in vascular regeneration.

PMID- 29467273
TI  - Cholesterol Depletion by TASIN-1 Induces Apoptotic Cell Death through the ER
      Stress/ROS/JNK Signaling in Colon Cancer Cells.
AB  - Truncated APC selective inhibitor-1 (TASIN-1) is a recently identified small
      molecule that selectively kills colorectal cancer cells that express truncated
      adenomatous polyposis coli (APC) by reducing cellular cholesterol levels.
      However, the downstream mechanism responsible for its cytotoxicity is not well
      understood. In this study, we show that TASIN-1 leads to apoptotic cell death via
      inducing ER stress-dependent JNK activation in human truncated APC colon cancer
      cells, accompanied by production of reactive oxygen species (ROS). In addition,
      TASIN-1 inhibits AKT activity through a cholesterol-dependent manner. Human colon
      tumor xenografts in immunodeficient mice also show the same TASIN-1 induced
      molecular mechanisms of tumor cell death as observed in vitro Taken together,
      cholesterol depletion by TASIN-1 treatment induces apoptotic cell death through
      activating ER stress/ROS/JNK axis and inhibiting AKT pro-survival signaling in
      colon cancer cells with truncated APC both in vitro and in vivoMol Cancer Ther;
      17(5); 943-51. (c)2018 AACR.

PMID- 29467274
TI  - JAK2 Inhibitor SAR302503 Abrogates PD-L1 Expression and Targets Therapy-Resistant
      Non-small Cell Lung Cancers.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide.
      Approximately 85% of all lung cancers are non-small cell histology [non-small
      cell lung cancer (NSCLC)]. Modern treatment strategies for NSCLC target driver
      oncogenes and immune checkpoints. However, less than 15% of patients survive
      beyond 5 years. Here, we investigated the effects of SAR302503 (SAR), a selective
      JAK2 inhibitor, on NSCLC cell lines and tumors. We show that SAR is cytotoxic to
      NSCLC cells, which exhibit resistance to genotoxic therapies, such as ionizing
      radiation, cisplatin, and etoposide. We demonstrate that constitutive IFN
      stimulated gene expression, including an IFN-related DNA damage resistance
      signature, predicts for sensitivity to SAR. Importantly, tumor cell-intrinsic
      expression of PD-L1 is IFN-inducible and abrogated by SAR. Taken together, these
      findings suggest potential dual roles for JAK2 inhibitors, both as a novel
      monotherapy in NSCLCs resistant to genotoxic therapies, and in tandem with immune
      checkpoint inhibition. Mol Cancer Ther; 17(4); 732-9. (c)2018 AACR.

PMID- 29467275
TI  - Pharmacological and Structural Characterizations of Naquotinib, a Novel Third
      Generation EGFR Tyrosine Kinase Inhibitor, in EGFR-Mutated Non-Small Cell Lung
      Cancer.
AB  - Multiple epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR
      TKI) have been developed to effectively inhibit EGFR-derived signals in non-small
      cell lung cancer (NSCLC). In this study, we assessed the efficacy of EGFR-TKIs,
      including a novel third-generation inhibitor naquotinib (ASP8273), in clinically
      relevant EGFR mutations, including L858R, exon 19 deletion, L858R+T790M, exon 19
      deletion+T790M with or without a C797S mutation, and several exon 20 insertion
      mutations. Using structural analyses, we also elucidated the mechanism of
      activation and sensitivity/resistance to EGFR-TKIs in EGFR exon 20 insertion
      mutations. The efficacy of naquotinib in cells with L858R, exon 19 deletion and
      exon 19 deletion+T790M was comparable with that of osimertinib. Interestingly,
      naquotinib was more potent than osimertinib for L858R+T790M. Additionally,
      naquotinib and osimertinib had comparable efficacy and a wide therapeutic window
      for cells with EGFR exon 20 insertions. Structural modeling partly elucidated the
      mechanism of activation and sensitivity/resistance to EGFR-TKIs in two EGFR exon
      20 insertion mutants, A767_V769dupASV and Y764_V765insHH. In summary, we have
      characterized the efficacy of EGFR-TKIs for NSCLC using in vitro and structural
      analyses and suggested the mechanism of activation and resistance to EGFR-TKIs of
      EGFR exon 20 insertion mutations. Our findings should guide the selection of
      appropriate EGFR-TKIs for the treatment of NSCLC with EGFR mutations and help
      clarify the biology of EGFR exon 20 insertion mutations. Mol Cancer Ther; 17(4);
      740-50. (c)2018 AACR.

PMID- 29467276
TI  - Neonatal Jaundice: Improved Quality and Cost Savings After Implementation of a
      Standard Pathway.
AB  - OBJECTIVES: Seattle Children's Hospital sought to optimize the value equation for
      neonatal jaundice patients by creating a standard care pathway. METHODS: An
      evidence-based pathway for management of neonatal jaundice was created. This
      included multidisciplinary team assembly, comprehensive literature review,
      creation of a treatment algorithm and computer order sets, formulation of goals
      and metrics, roll-out of an education program for end users, and ongoing pathway
      improvement. The pathway was implemented on May 31, 2012. Quality metrics before
      and after implementation were compared. External data were used to analyze cost
      impacts. RESULTS: Significant improvements were achieved across multiple quality
      dimensions. Time to recovery decreased: mean length of stay was 1.30 days for 117
      prepathway patients compared with 0.87 days for 69 postpathway patients (P <
      .001). Efficiency was enhanced: mean time to phototherapy initiation was 101.26
      minutes for 14 prepathway patients compared with 54.67 minutes for 67 postpathway
      patients (P = .03). Care was less invasive: intravenous fluid orders were reduced
      from 80% to 44% (P < .001). Inpatient use was reduced: 66% of prepathway patients
      were admitted from the emergency department to inpatient care, compared with 50%
      of postpathway patients (P = .01). There was no increase in the readmission rate.
      These achievements translated to statistically significant cost reductions in
      total charges, as well as in the following categories: intravenous fluids,
      laboratory, room cost, and emergency department charges. CONCLUSIONS: An evidence
      based standard care pathway for neonatal jaundice can significantly improve
      multiple dimensions of value, including reductions in cost and length of stay.

PMID- 29467277
TI  - Reducing Youth Firearm Suicide Risk: Evidence for Opportunities.

PMID- 29467278
TI  - Television Format and Children's Executive Function.

PMID- 29467279
TI  - Firearm Storage in Homes With Children With Self-Harm Risk Factors.
AB  - OBJECTIVES: To describe firearm storage practices in homes with children who have
      versus do not have self-harm risk factors. METHODS: A cross-sectional analysis of
      a nationally representative probability-based online survey of US adults
      conducted in 2015 (n = 3949; response rate 55%). Respondents self-reported
      whether they lived with children and were a caretaker/health care decision-maker
      for a child. Household firearm ownership was ascertained for all respondents; how
      firearms were stored in homes with guns was asked of gun owning respondents only;
      all respondents were asked whether their child had a history of the following
      self-harm risk factors: depression, mental health conditions other than
      depression, or attention-deficit/hyperactivity disorder. RESULTS: Household
      firearms were present in 43.5% (95% confidence interval [CI]: 34.4-64.7) of homes
      with children who had a history of self-harm risk factors (n = 52), compared with
      42.3% (95% CI: 35.2-49.7) of homes in which no child had self-harm risk factors
      (n = 411). Among parents or caretakers with firearms, 34.9% (95 % CI: 20.2-53.2)
      stored all guns locked and unloaded when they had a child with a history self
      harm risk factors, compared with 31.8% (95% CI: 25.9-38.3) when none of their
      children had such a history. CONCLUSIONS: Millions of US children live in homes
      in which firearms are left loaded or unlocked or both. A child's history of
      depression, mental health conditions other than depression, or attention
      deficit/hyperactivity disorder does not appear to appreciably influence caretaker
      decisions about whether to (1) have firearms in the home, or (2) store all
      household firearms in accordance with American Academy of Pediatrics
      recommendations (ie, locked and unloaded).

PMID- 29467280
TI  - Monkey see, Humans Won't Do-the misguided reaction to the first cloning of
      primates.

PMID- 29467281
TI  - The MYO6 interactome reveals adaptor complexes coordinating early endosome and
      cytoskeletal dynamics.
AB  - The intracellular functions of myosin motors requires a number of adaptor
      molecules, which control cargo attachment, but also fine-tune motor activity in
      time and space. These motor-adaptor-cargo interactions are often weak, transient
      or highly regulated. To overcome these problems, we use a proximity labelling
      based proteomics strategy to map the interactome of the unique minus end-directed
      actin motor MYO6. Detailed biochemical and functional analysis identified several
      distinct MYO6-adaptor modules including two complexes containing RhoGEFs: the
      LIFT (LARG-Induced F-actin for Tethering) complex that controls endosome
      positioning and motility through RHO-driven actin polymerisation; and the DISP
      (DOCK7-Induced Septin disPlacement) complex, a novel regulator of the septin
      cytoskeleton. These complexes emphasise the role of MYO6 in coordinating endosome
      dynamics and cytoskeletal architecture. This study provides the first in vivo
      interactome of a myosin motor protein and highlights the power of this approach
      in uncovering dynamic and functionally diverse myosin motor complexes.

PMID- 29467282
TI  - Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c
      Myc function.
AB  - Valosin-containing protein (VCP) is an evolutionarily conserved ubiquitin
      dependent ATPase that mediates the degradation of proteins through the ubiquitin
      proteasome pathway. Despite the central role of VCP in the regulation of protein
      homeostasis, identity and nature of its cellular substrates remain poorly
      defined. Here, we combined chemical inhibition of VCP and quantitative ubiquitin
      remnant profiling to assess the effect of VCP inhibition on the ubiquitin
      modified proteome and to probe the substrate spectrum of VCP in human cells. We
      demonstrate that inhibition of VCP perturbs cellular ubiquitylation and increases
      ubiquitylation of a different subset of proteins compared to proteasome
      inhibition. VCP inhibition globally upregulates K6-linked ubiquitylation that is
      dependent on the HECT-type ubiquitin E3 ligase HUWE1. We report ~450 putative VCP
      substrates, many of which function in nuclear processes, including gene
      expression, DNA repair and cell cycle. Moreover, we identify that VCP regulates
      the level and activity of the transcription factor c-Myc.

PMID- 29467283
TI  - Activation of hypothalamic RIP-Cre neurons promotes beiging of WAT via
      sympathetic nervous system.
AB  - Activation of brown adipose tissue (BAT) and beige fat by cold increases energy
      expenditure. Although their activation is known to be differentially regulated in
      part by hypothalamus, the underlying neural pathways and populations remain
      poorly characterized. Here, we show that activation of rat-insulin-promoter-Cre
      (RIP-Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes
      recruitment of beige fat via a selective control of sympathetic nervous system
      (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on
      BAT Genetic ablation of APPL2 in RIP-Cre neurons diminishes beiging in sWAT
      without affecting BAT, leading to cold intolerance and obesity in mice. Such
      defects are reversed by activation of RIP-Cre neurons, inactivation of VMH AMPK,
      or treatment with a beta3-adrenergic receptor agonist. Hypothalamic APPL2
      enhances neuronal activation in VMH RIP-Cre neurons and raphe pallidus, thereby
      eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that
      beige fat can be selectively activated by VMH RIP-Cre neurons, in which the APPL2
      AMPK signaling axis is crucial for this defending mechanism to cold and obesity.

PMID- 29467284
TI  - Adult-born neurons boost odor-reward association.
AB  - Olfaction is an important sensory modality driving fundamental behaviors. During
      odor-dependent learning, a positive value is commonly assigned to an odorant, and
      multiple forms of plasticity are involved when such odor-reward associations are
      formed. In rodents, one of the mechanisms underlying plasticity in the olfactory
      bulb consists in recruiting new neurons daily throughout life. However, it is
      still unknown whether adult-born neurons might participate in encoding odor
      value. Here, we demonstrate that exposure to reward-associated odors specifically
      increases activity of adult-born neurons but not preexisting neurons. Remarkably,
      adult-born neuron activation during rewarded odor presentation heightens
      discrimination learning and enhances the ability to update the odor value during
      reversal association. Moreover, in some cases, activation of this interneuron
      population can trigger olfactory learning without sensory stimulation. Taken
      together, our results show a specific involvement of adult-born neurons in
      facilitating odor-reward association during adaptive learning.

PMID- 29467285
TI  - Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA.
AB  - Endothelial cell (EC)-enriched protein coding genes, such as endothelial nitric
      oxide synthase (eNOS), define quintessential EC-specific physiologic functions.
      It is not clear whether long noncoding RNAs (lncRNAs) also define cardiovascular
      cell type-specific phenotypes, especially in the vascular endothelium. Here, we
      report the existence of a set of EC-enriched lncRNAs and define a role for
      spliced-transcript endothelial-enriched lncRNA (STEEL) in angiogenic potential,
      macrovascular/microvascular identity, and shear stress responsiveness. STEEL is
      expressed from the terminus of the HOXD locus and is transcribed antisense to
      HOXD transcription factors. STEEL RNA increases the number and integrity of de
      novo perfused microvessels in an in vivo model and augments angiogenesis in
      vitro. The STEEL RNA is polyadenylated, nuclear enriched, and has microvascular
      predominance. Functionally, STEEL regulates a number of genes in diverse ECs. Of
      interest, STEEL up-regulates both eNOS and the transcription factor Kruppel-like
      factor 2 (KLF2), and is subject to feedback inhibition by both eNOS and shear
      augmented KLF2. Mechanistically, STEEL up-regulation of eNOS and KLF2 is
      transcriptionally mediated, in part, via interaction of chromatin-associated
      STEEL with the poly-ADP ribosylase, PARP1. For instance, STEEL recruits PARP1 to
      the KLF2 promoter. This work identifies a role for EC-enriched lncRNAs in the
      phenotypic adaptation of ECs to both body position and hemodynamic forces and
      establishes a newer role for lncRNAs in the transcriptional regulation of EC
      identity.

PMID- 29467286
TI  - Viral insulin-like peptides activate human insulin and IGF-1 receptor signaling:
      A paradigm shift for host-microbe interactions.
AB  - Viruses are the most abundant biological entities and carry a wide variety of
      genetic material, including the ability to encode host-like proteins. Here we
      show that viruses carry sequences with significant homology to several human
      peptide hormones including insulin, insulin-like growth factors (IGF)-1 and -2,
      FGF-19 and -21, endothelin-1, inhibin, adiponectin, and resistin. Among the
      strongest homologies were those for four viral insulin/IGF-1-like peptides
      (VILPs), each encoded by a different member of the family Iridoviridae VILPs show
      up to 50% homology to human insulin/IGF-1, contain all critical cysteine
      residues, and are predicted to form similar 3D structures. Chemically synthesized
      VILPs can bind to human and murine IGF-1/insulin receptors and stimulate receptor
      autophosphorylation and downstream signaling. VILPs can also increase glucose
      uptake in adipocytes and stimulate the proliferation of fibroblasts, and
      injection of VILPs into mice significantly lowers blood glucose. Transfection of
      mouse hepatocytes with DNA encoding a VILP also stimulates insulin/IGF-1
      signaling and DNA synthesis. Human microbiome studies reveal the presence of
      these Iridoviridae in blood and fecal samples. Thus, VILPs are members of the
      insulin/IGF superfamily with the ability to be active on human and rodent cells,
      raising the possibility for a potential role of VILPs in human disease.
      Furthermore, since only 2% of viruses have been sequenced, this study raises the
      potential for discovery of other viral hormones which, along with known virally
      encoded growth factors, may modify human health and disease.

PMID- 29467287
TI  - Revealing nascent proteomics in signaling pathways and cell differentiation.
AB  - Regulation of gene expression at the level of protein synthesis is a crucial
      element in driving how the genetic landscape is expressed. However, we are still
      limited in technologies that can quantitatively capture the immediate proteomic
      changes that allow cells to respond to specific stimuli. Here, we present a
      method to capture and identify nascent proteomes in situ across different cell
      types without disturbing normal growth conditions, using O-propargyl-puromycin
      (OPP). Cell-permeable OPP rapidly labels nascent elongating polypeptides, which
      are subsequently conjugated to biotin-azide, using click chemistry, and captured
      with streptavidin beads, followed by digestion and analysis, using liquid
      chromatography-tandem mass spectrometry. Our technique of OPP-mediated
      identification (OPP-ID) allows detection of widespread proteomic changes within a
      short 2-hour pulse of OPP. We illustrate our technique by recapitulating
      alterations of proteomic networks induced by a potent mammalian target of
      rapamycin inhibitor, MLN128. In addition, by employing OPP-ID, we identify more
      than 2,100 proteins and uncover distinct protein networks underlying early
      erythroid progenitor and differentiation states not amenable to alternative
      approaches such as amino acid analog labeling. We present OPP-ID as a method to
      quantitatively identify nascent proteomes across an array of biological contexts
      while preserving the subtleties directing signaling in the native cellular
      environment.

PMID- 29467288
TI  - Molecular basis for diversification of yeast prion strain conformation.
AB  - Self-propagating beta-sheet-rich fibrillar protein aggregates, amyloid fibers,
      are often associated with cellular dysfunction and disease. Distinct amyloid
      conformations dictate different physiological consequences, such as cellular
      toxicity. However, the origin of the diversity of amyloid conformation remains
      unknown. Here, we suggest that altered conformational equilibrium in natively
      disordered monomeric proteins leads to the adaptation of alternate amyloid
      conformations that have different phenotypic effects. We performed a
      comprehensive high-resolution structural analysis of Sup35NM, an N-terminal
      fragment of the Sup35 yeast prion protein, and found that monomeric Sup35NM
      harbored latent local compact structures despite its overall disordered
      conformation. When the hidden local microstructures were relaxed by genetic
      mutations or solvent conditions, Sup35NM adopted a strikingly different amyloid
      conformation, which redirected chaperone-mediated fiber fragmentation and
      modulated prion strain phenotypes. Thus, dynamic conformational fluctuations in
      natively disordered monomeric proteins represent a posttranslational mechanism
      for diversification of aggregate structures and cellular phenotypes.

PMID- 29467290
TI  - New sources for the emergence of new invaders.

PMID- 29467289
TI  - Protonation state of inhibitors determines interaction sites within voltage-gated
      sodium channels.
AB  - Voltage-gated sodium channels are essential for carrying electrical signals
      throughout the body, and mutations in these proteins are responsible for a
      variety of disorders, including epilepsy and pain syndromes. As such, they are
      the target of a number of drugs used for reducing pain or combatting arrhythmias
      and seizures. However, these drugs affect all sodium channel subtypes found in
      the body. Designing compounds to target select sodium channel subtypes will
      provide a new therapeutic pathway and would maximize treatment efficacy while
      minimizing side effects. Here, we examine the binding preferences of nine
      compounds known to be sodium channel pore blockers in molecular dynamics
      simulations. We use the approach of replica exchange solute tempering (REST) to
      gain a more complete understanding of the inhibitors' behavior inside the pore of
      NavMs, a bacterial sodium channel, and NavPas, a eukaryotic sodium channel. Using
      these simulations, we are able to show that both charged and neutral compounds
      partition into the bilayer, but neutral forms more readily cross it. We show that
      there are two possible binding sites for the compounds: (i) a site on helix 6,
      which has been previously determined by many experimental and computational
      studies, and (ii) an additional site, occupied by protonated compounds in which
      the positively charged part of the drug is attracted into the selectivity filter.
      Distinguishing distinct binding poses for neutral and charged compounds is
      essential for understanding the nature of pore block and will aid the design of
      subtype-selective sodium channel inhibitors.

PMID- 29467292
TI  - Trophic redundancy reduces vulnerability to extinction cascades.
AB  - Current species extinction rates are at unprecedentedly high levels. While human
      activities can be the direct cause of some extinctions, it is becoming
      increasingly clear that species extinctions themselves can be the cause of
      further extinctions, since species affect each other through the network of
      ecological interactions among them. There is concern that the simplification of
      ecosystems, due to the loss of species and ecological interactions, increases
      their vulnerability to such secondary extinctions. It is predicted that more
      complex food webs will be less vulnerable to secondary extinctions due to greater
      trophic redundancy that can buffer against the effects of species loss. Here, we
      demonstrate in a field experiment with replicated plant-insect communities, that
      the probability of secondary extinctions is indeed smaller in food webs that
      include trophic redundancy. Harvesting one species of parasitoid wasp led to
      secondary extinctions of other, indirectly linked, species at the same trophic
      level. This effect was markedly stronger in simple communities than for the same
      species within a more complex food web. We show that this is due to functional
      redundancy in the more complex food webs and confirm this mechanism with a food
      web simulation model by highlighting the importance of the presence and strength
      of trophic links providing redundancy to those links that were lost. Our results
      demonstrate that biodiversity loss, leading to a reduction in redundant
      interactions, can increase the vulnerability of ecosystems to secondary
      extinctions, which, when they occur, can then lead to further simplification and
      run-away extinction cascades.

PMID- 29467291
TI  - Epigenetic alterations in longevity regulators, reduced life span, and
      exacerbated aging-related pathology in old father offspring mice.
AB  - Advanced age is not only a major risk factor for a range of disorders within an
      aging individual but may also enhance susceptibility for disease in the next
      generation. In humans, advanced paternal age has been associated with increased
      risk for a number of diseases. Experiments in rodent models have provided initial
      evidence that paternal age can influence behavioral traits in offspring animals,
      but the overall scope and extent of paternal age effects on health and disease
      across the life span remain underexplored. Here, we report that old father
      offspring mice showed a reduced life span and an exacerbated development of aging
      traits compared with young father offspring mice. Genome-wide epigenetic analyses
      of sperm from aging males and old father offspring tissue identified
      differentially methylated promoters, enriched for genes involved in the
      regulation of evolutionarily conserved longevity pathways. Gene expression
      analyses, biochemical experiments, and functional studies revealed evidence for
      an overactive mTORC1 signaling pathway in old father offspring mice.
      Pharmacological mTOR inhibition during the course of normal aging ameliorated
      many of the aging traits that were exacerbated in old father offspring mice.
      These findings raise the possibility that inherited alterations in longevity
      pathways contribute to intergenerational effects of aging in old father offspring
      mice.

PMID- 29467293
TI  - Reply to Kardos et al.: Estimation of inbreeding depression from SNP data.

PMID- 29467294
TI  - How should we compare different genomic estimates of the strength of inbreeding
      depression?

PMID- 29467295
TI  - Reply to Masin et al: To be or not to be a phospholipase A.

PMID- 29467296
TI  - Phospholipase A activity of adenylate cyclase toxin?

PMID- 29467297
TI  - Eosinophil depletion suppresses radiation-induced small intestinal fibrosis.
AB  - Radiation-induced intestinal fibrosis (RIF) is a serious complication after
      abdominal radiotherapy for pelvic tumor or peritoneal metastasis. Herein, we show
      that RIF is mediated by eosinophil interactions with alpha-smooth muscle actin
      positive (alpha-SMA+) stromal cells. Abdominal irradiation caused RIF especially
      in the submucosa (SM) of the small intestine, which was associated with the
      excessive accumulation of eosinophils in both human and mouse. Eosinophil
      deficient mice showed markedly ameliorated RIF, suggesting the importance of
      eosinophils. After abdominal irradiation, chronic crypt cell death caused
      elevation of extracellular adenosine triphosphate, which in turn activated
      expression of C-C motif chemokine 11 (CCL11) by pericryptal alpha-SMA+ cells in
      the SM to attract eosinophils in mice. Inhibition of C-C chemokine receptor 3
      (CCR3) by genetic deficiency or neutralizing antibody (Ab) treatment suppressed
      eosinophil accumulation in the SM after irradiation in mice, suggesting a
      critical role of the CCL11/CCR3 axis in the eosinophil recruitment. Activated
      alpha-SMA+ cells also expressed granulocyte-macrophage colony-stimulating factor
      (GM-CSF) to activate eosinophils. Transforming growth factor-beta1 from GM-CSF
      stimulated eosinophils promoted collagen expression by alpha-SMA+ cells. In
      translational studies, treatment with a newly developed interleukin-5 receptor
      alpha-targeting Ab, analogous to the human agent benralizumab, depleted
      intestinal eosinophils and suppressed RIF in mice. Collectively, we identified
      eosinophils as a crucial factor in the pathogenesis of RIF and showed potential
      therapeutic strategies for RIF by targeting eosinophils.

PMID- 29467299
TI  - In situ formed reactive oxygen species-responsive scaffold with gemcitabine and
      checkpoint inhibitor for combination therapy.
AB  - Patients with low-immunogenic tumors respond poorly to immune checkpoint blockade
      (ICB) targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)
      pathway. Conversely, patients responding to ICB can experience various side
      effects. We have thus engineered a therapeutic scaffold that, when formed in
      situ, allows the local release of gemcitabine (GEM) and an anti-PD-L1 blocking
      antibody (aPDL1) with distinct release kinetics. The scaffold consists of
      reactive oxygen species (ROS)-degradable hydrogel that releases therapeutics in a
      programmed manner within the tumor microenvironment (TME), which contains
      abundant ROS. We found that the aPDL1-GEM scaffold elicits an immunogenic tumor
      phenotype and promotes an immune-mediated tumor regression in the tumor-bearing
      mice, with prevention of tumor recurrence after primary resection.

PMID- 29467298
TI  - Microhemorrhage-associated tissue iron enhances the risk for Aspergillus
      fumigatus invasion in a mouse model of airway transplantation.
AB  - Invasive pulmonary disease due to the mold Aspergillus fumigatus can be life
      threatening in lung transplant recipients, but the risk factors remain poorly
      understood. To study this process, we used a tracheal allograft mouse model that
      recapitulates large airway changes observed in patients undergoing lung
      transplantation. We report that microhemorrhage-related iron content may be a
      major determinant of A. fumigatus invasion and, consequently, its virulence.
      Invasive growth was increased during progressive alloimmune-mediated graft
      rejection associated with high concentrations of ferric iron in the graft. The
      role of iron in A. fumigatus invasive growth was further confirmed by showing
      that this invasive phenotype was increased in tracheal transplants from donor
      mice lacking the hemochromatosis gene (Hfe-/- ). The invasive phenotype was also
      increased in mouse syngrafts treated with topical iron solution and in allograft
      recipients receiving deferoxamine, a chelator that increases iron bioavailability
      to the mold. The invasive growth of the iron-intolerant A. fumigatus double
      knockout mutant (DeltasreA/DeltacccA) was lower than that of the wild-type mold.
      Alloimmune-mediated microvascular damage and iron overload did not appear to
      impair the host's immune response. In human lung transplant recipients, positive
      staining for iron in lung transplant tissue was more commonly seen in
      endobronchial biopsy sections from transplanted airways than in biopsies from the
      patients' own airways. Collectively, these data identify iron as a major
      determinant of A. fumigatus invasive growth and a potential target to treat or
      prevent A. fumigatus infections in lung transplant patients.

PMID- 29467300
TI  - High-throughput metabolomic analysis predicts mode of action of uncharacterized
      antimicrobial compounds.
AB  - Rapidly spreading antibiotic resistance and the low discovery rate of new
      antimicrobial compounds demand more effective strategies for early drug
      discovery. One bottleneck in the drug discovery pipeline is the identification of
      the modes of action (MoAs) of new compounds. We have developed a rapid systematic
      metabolome profiling strategy to classify the MoAs of bioactive compounds. The
      method predicted MoA-specific metabolic responses in the nonpathogenic bacterium
      Mycobacterium smegmatis after treatment with 62 reference compounds with known
      MoAs and different metabolic and nonmetabolic targets. We then analyzed a library
      of 212 new antimycobacterial compounds with unknown MoAs from a drug discovery
      effort by the pharmaceutical company GlaxoSmithKline (GSK). More than 70% of
      these new compounds induced metabolic responses in M. smegmatis indicative of
      known MoAs, seven of which were experimentally validated. Only 8% (16) of the
      compounds appeared to target unconventional cellular processes, illustrating the
      difficulty in discovering new antibiotics with different MoAs among compounds
      used as monotherapies. For six of the GSK compounds with potentially new MoAs,
      the metabolome profiles suggested their ability to interfere with trehalose and
      lipid metabolism. This was supported by whole-genome sequencing of spontaneous
      drug-resistant mutants of the pathogen Mycobacterium tuberculosis and in vitro
      compound-proteome interaction analysis for one of these compounds. Our compendium
      of drug-metabolome profiles can be used to rapidly query the MoAs of
      uncharacterized antimicrobial compounds and should be a useful resource for the
      drug discovery community.

PMID- 29467302
TI  - Alzheimer disease biomarkers and synucleinopathy.

PMID- 29467303
TI  - Focal myositis: New insights on diagnosis and pathology.
AB  - OBJECTIVE: To better define in a cohort study the clinical and pathologic
      features of focal myositis (FM). METHODS: With the use of the usual
      clinicopathologic definition, each confirmed case of FM in the Lyon University
      Hospital's myopathologic database between 2000 and 2016 was retrieved. Clinical,
      pathologic, imaging, serologic, and therapeutic data were collected. When data
      were missing but feasible, appropriate pathologic analyses were performed.
      RESULTS: Of the 924 patients included in the database, 37 (4%) had confirmed FM
      (14 female, 23 male patients). The main symptoms were pain (n = 30, 81%),
      muscular mass (n = 16, 43%), erythema at the site of FM (n = 12, 32%), and fever
      (n = 9, 24%). Serum creatine kinase was normal in most patients (81%); serum
      immune abnormalities were frequent (inflammatory syndrome in sera [39%],
      dysglobulinemia [52%], and anti-nuclear antibody positivity [29%]). In addition
      to confirming previously reported findings, pathologic analyses found significant
      rates of vasculitis (68%) and fasciitis (73%). Here, FM appeared frequently to be
      associated with other diseases such as immune-mediated inflammatory disease
      (IMID; 32%), neoplasia (24%), and radiculopathy (11%). Regarding outcomes, 64% of
      the cases had received immunosuppressive drugs, and the relapse rate was 41%.
      CONCLUSION: The present study suggests that FM is not as innocuous as previously
      believed, particularly considering the associated disorders. Notably, patients
      with FM should receive careful IMID and neoplasia screening.

PMID- 29467304
TI  - Association between implementation of a code stroke system and poststroke
      epilepsy.
AB  - OBJECTIVE: We aimed to investigate the effect of a code stroke system on the
      development of poststroke epilepsy. METHODS: We retrospectively analyzed
      consecutive patients treated with IV thrombolysis under or outside the code
      stroke system between 2003 and 2012. Patients were followed up for at least 2
      years or until death. Factors with p < 0.1 in univariate comparisons were
      selected for multivariable logistic and Cox regression. RESULTS: A total of 409
      patients met the eligibility criteria. Their median age at stroke onset was 75
      years (interquartile range 64-83 years); 220 (53.8%) were male. The median follow
      up duration was 1,074 days (interquartile range 119-1,671 days). Thirty-two
      patients (7.8%) had poststroke seizures during follow-up, comprising 7 (1.7%)
      with acute symptomatic seizures and 25 (6.1%) with late-onset seizures. Twenty
      six patients (6.4%) fulfilled the definition of poststroke epilepsy. Three
      hundred eighteen patients (77.8%) were treated with the code stroke system while
      91 (22.2%) were not. After adjustment for age and stroke etiology, use of the
      code stroke system was associated with decreased odds of poststroke epilepsy
      (odds ratio = 0.36, 95% confidence interval 0.14-0.87, p = 0.024). Cox regression
      showed lower adjusted hazard rates for poststroke epilepsy within 5 years for
      patients managed under the code stroke system (hazard ratio = 0.60, 95%
      confidence interval 0.47-0.79, p < 0.001). CONCLUSION: The code stroke system was
      associated with reduced odds and instantaneous risk of poststroke epilepsy.
      Further studies are required to identify the contribution of the individual
      components and mechanisms against epileptogenesis after stroke. CLASSIFICATION OF
      EVIDENCE: This study provides Class III evidence that for people with acute
      ischemic stroke, implementation of a code stroke system reduces the risk of
      poststroke epilepsy.

PMID- 29467301
TI  - Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in
      myeloproliferative neoplasms.
AB  - Recent evidence has revealed that oncogenic mutations may confer immune escape. A
      better understanding of how an oncogenic mutation affects immunosuppressive
      programmed death ligand 1 (PD-L1) expression may help in developing new
      therapeutic strategies. We show that oncogenic JAK2 (Janus kinase 2) activity
      caused STAT3 (signal transducer and activator of transcription 3) and STAT5
      phosphorylation, which enhanced PD-L1 promoter activity and PD-L1 protein
      expression in JAK2V617F-mutant cells, whereas blockade of JAK2 reduced PD-L1
      expression in myeloid JAK2V617F-mutant cells. PD-L1 expression was higher on
      primary cells isolated from patients with JAK2V617F-myeloproliferative neoplasms
      (MPNs) compared to healthy individuals and declined upon JAK2 inhibition.
      JAK2V617F mutational burden, pSTAT3, and PD-L1 expression were highest in primary
      MPN patient-derived monocytes, megakaryocytes, and platelets. PD-1 (programmed
      death receptor 1) inhibition prolonged survival in human MPN xenograft and
      primary murine MPN models. This effect was dependent on T cells. Mechanistically,
      PD-L1 surface expression in JAK2V617F-mutant cells affected metabolism and cell
      cycle progression of T cells. In summary, we report that in MPN, constitutive
      JAK2/STAT3/STAT5 activation, mainly in monocytes, megakaryocytes, and platelets,
      caused PD-L1-mediated immune escape by reducing T cell activation, metabolic
      activity, and cell cycle progression. The susceptibility of JAK2V617F-mutant MPN
      to PD-1 targeting paves the way for immunomodulatory approaches relying on PD-1
      inhibition.

PMID- 29467306
TI  - Gait analysis in PSP and NPH: Dual-task conditions make the difference.
AB  - OBJECTIVE: To test whether quantitative gait analysis of gait under single- and
      dual-task conditions can be used for a differential diagnosis of progressive
      supranuclear palsy (PSP) and idiopathic normal-pressure hydrocephalus (iNPH).
      METHODS: In this cross-sectional study, temporal and spatial gait parameters were
      analyzed in 38 patients with PSP (Neurological Disorders and Stroke and Society
      for Progressive Supranuclear Palsy diagnostic criteria), 27 patients with iNPH
      (international iNPH guidelines), and 38 healthy controls. A pressure-sensitive
      carpet was used to examine gait under 5 conditions: single task (preferred, slow,
      and maximal speed), cognitive dual task (walking with serial 7 subtractions), and
      motor dual task (walking while carrying a tray). RESULTS: The main results were
      as follows. First, both patients with PSP and those with iNPH exhibited
      significant gait dysfunction, which was worse in patients with iNPH with a more
      broad-based gait (p < 0.001). Second, stride time variability was increased in
      both patient groups, more pronounced in PSP (p = 0.009). Third, cognitive dual
      task led to a greater reduction of gait velocity in PSP (PSP 34.4% vs iNPH 16.9%,
      p = 0.002). Motor dual task revealed a dissociation of gait performance: patients
      with PSP considerably worsened, but patients with iNPH tended to improve.
      CONCLUSION: Patients with PSP seem to be more sensitive to dual-task
      perturbations than patients with iNPH. An increased step width and anisotropy of
      the effect of dual-task conditions (cognitive vs motor) seem to be good
      diagnostic tools for iNPH.

PMID- 29467305
TI  - CSF tau and beta-amyloid predict cerebral synucleinopathy in autopsied Lewy body
      disorders.
AB  - OBJECTIVE: To test the association of antemortem CSF biomarkers with postmortem
      pathology in Lewy body disorders (LBD). METHODS: Patients with autopsy-confirmed
      LBD (n = 24) and autopsy-confirmed Alzheimer disease (AD) (n = 23) and
      cognitively normal (n = 36) controls were studied. In LBD, neuropathologic
      criteria defined Lewy body alpha-synuclein (SYN) stages with medium/high AD
      copathology (SYN + AD = 10) and low/no AD copathology (SYN - AD = 14). Ordinal
      pathology scores for tau, beta-amyloid (Abeta), and SYN pathology were averaged
      across 7 cortical regions to obtain a global cerebral score for each pathology.
      CSF total tau (t-tau), phosphorylated tau at threonine181, and Abeta1-42 levels
      were compared between LBD and control groups and correlated with global cerebral
      pathology scores in LBD with linear regression. Diagnostic accuracy for
      postmortem categorization of LBD into SYN + AD vs SYN - AD or neocortical vs
      brainstem/limbic SYN stage was tested with receiver operating curves. RESULTS:
      SYN + AD had higher CSF t-tau (mean difference 27.0 +/- 8.6 pg/mL) and lower
      Abeta1-42 (mean difference -84.0 +/- 22.9 g/mL) compared to SYN - AD (p < 0.01,
      both). Increasing global cerebral tau and plaque scores were associated with
      higher CSF t-tau (R2 = 0.15-0.16, p < 0.05, both) and lower Abeta1-42 (R2 = 0.43
      0.49, p < 0.001, both), while increasing cerebral SYN scores were associated with
      lower CSF Abeta1-42 (R2 = 0.31, p < 0.001) and higher CSF t-tau/Abeta1-42 ratio
      (R2 = 0.27, p = 0.01). CSF t-tau/Abeta1-42 ratio had 100% specificity and 90%
      sensitivity for SYN + AD, and CSF Abeta1-42 had 77% specificity and 82%
      sensitivity for neocortical SYN stage. CONCLUSIONS: Higher antemortem CSF t
      tau/Abeta1-42 and lower Abeta1-42 levels are predictive of increasing cerebral AD
      and SYN pathology. These biomarkers may identify patients with LBD vulnerable to
      cortical SYN pathology who may benefit from both SYN and AD-targeted disease
      modifying therapies.

PMID- 29467307
TI  - Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple
      sclerosis.
AB  - OBJECTIVE: To assess safety, tolerability, and efficacy of the antigen-specific
      immunotherapy ATX-MS-1467 in participants with relapsing multiple sclerosis using
      different treatment protocols to induce tolerance. METHODS: Two open-label trials
      in adult participants with relapsing multiple sclerosis were conducted. Study 1
      was a multicenter, phase 1b safety evaluation comparing intradermal (i.d.)
      (cohort 1) with subcutaneous (cohort 2) administration in 43 participants. Both
      cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 MUg at 14-day
      intervals over 8 weeks, followed by 8 weeks with 4 additional 800-MUg doses at 14
      day intervals and 32 weeks off study medication. Study 2 was a phase 2a,
      multicenter, single-arm trial enrolling 37 participants. ATX-MS-1467 was titrated
      from 50 MUg i.d. on day 1 to 200 MUg on day 15 and 800 MUg on day 29 followed by
      biweekly administration of 800 MUg for 16 weeks and 16 weeks off study
      medication. Efficacy was evaluated on MRI parameters and clinical variables.
      Safety endpoints included treatment-emergent adverse events and injection-site
      reactions. RESULTS: In study 1, there was a significant decrease in
      new/persisting T1 gadolinium-enhanced (GdE) lesions in cohort 1 from baseline to
      week 16, returning to baseline values at week 48. In study 2, the number of T1
      GdE lesions were significantly reduced on treatment and remained reduced at study
      completion. Safety results were unremarkable in both studies. CONCLUSION:
      Relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment
      period is associated with reduction in GdE lesions and a sustained effect post
      treatment. Further trials of ATX-MS-1467 are warranted. CLASSIFICATION OF
      EVIDENCE: This work provides Class IV evidence that for patients with relapsing
      multiple sclerosis, slow ATX-MS-1467 titration and a longer full-dose i.d.
      treatment period is associated with reduction in GdE lesions.

PMID- 29467309
TI  - Higher CYP2E1 Activity Correlates with Hepatocarcinogenesis Induced by
      Diethylnitrosamine.
AB  - Hepatocellular carcinoma (HCC) is one of the most common types of primary liver
      cancer and the third most frequent cause of cancer death worldwide.
      Diethylnitrosamine (DEN) is one of the recognized risk factors for
      hepatocarcinogenesis likely due to CYP2E1-mediated metabolic activation. However,
      CYP2E1-mediated DEN metabolic activity in non-neoplastic liver tissue from HCC
      patients has not been determined; the role of CYP2E1 activity, in particular
      CYP2E1 constitutive activity and CYP2E1 inhibited activity, with respect to the
      hepatocarcinogenesis induced by DEN is not yet clear. Herein, we determined
      CYP2E1-mediated DEN metabolic activity in non-neoplastic liver tissue from HCC
      patients and found that CYP2E1-mediated DEN metabolic activity was significantly
      elevated with a 43.3% positive rate, and clinicopathologic parameters did not
      affect the activity. Then, using a Sprague-Dawley rat liver tumor model induced
      by DEN, the relationship between CYP2E1 constitutive/inhibited activity and
      hepatocarcinogenesis was explored. The results showed that the CYP2E1
      constitutive activity was strongly correlated with tumor incidence and severity
      of liver tumorigenesis (nodule numbers and size), whereas inhibition of CYP2E1
      activity decreased hepatocyte proliferation, liver injury, and liver
      carcinogenesis in the presence of DEN. In conclusion, the higher CYP2E1 activity
      would lead to an increased incidence of HCC as a result of CYP2E1-mediated DEN
      activation. Therefore, higher CYP2E1 activity might be a risk factor for HCC
      induced by DEN.

PMID- 29467308
TI  - Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam,
      Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model
      Relevant to the Pediatric Population.
AB  - The currently Food and Drug Administration-approved anticonvulsant for the
      treatment of status epilepticus (SE) induced by nerve agents is the
      benzodiazepine diazepam; however, diazepam does not appear to offer
      neuroprotective benefits. This is of particular concern with respect to the
      protection of children because, in the developing brain, synaptic transmission
      mediated via GABAA receptors, the target of diazepam, is weak. In the present
      study, we exposed 21-day-old male rats to 1.2 * LD50 soman and compared the
      antiseizure, antilethality, and neuroprotective efficacy of diazepam (10 mg/kg),
      LY293558 (an AMPA/GluK1 receptor antagonist; 15 mg/kg), caramiphen (CRM, an
      antimuscarinic with NMDA receptor-antagonistic properties; 50 mg/kg), and
      LY293558 (15 mg/kg) + CRM (50 mg/kg), administered 1 hour after exposure.
      Diazepam, LY293558, and LY293558 + CRM, but not CRM alone, terminated SE;
      LY293558 + CRM treatment acted significantly faster and produced a survival rate
      greater than 85%. Thirty days after soman exposure, neurodegeneration in limbic
      regions was most severe in the CRM-treated group, minimal to severe-depending on
      the region-in the diazepam group, absent to moderate in the LY293558-treated
      group, and totally absent in the LY293558 + CRM group. Amygdala and hippocampal
      atrophy, a severe reduction in spontaneous inhibitory activity in the basolateral
      amygdala, and increased anxiety-like behavior in the open-field and acoustic
      startle response tests were present in the diazepam and CRM groups, whereas the
      LY293558 and LY293558 + CRM groups did not differ from controls. The combined
      administration of LY293558 and CRM, by blocking mainly AMPA, GluK1, and NMDA
      receptors, is a very effective anticonvulsant and neuroprotective therapy against
      soman in young rats.

PMID- 29467310
TI  - Whole-Body but Not Hepatic Knockdown of Chemerin by Antisense Oligonucleotide
      Decreases Blood Pressure in Rats.
AB  - Chemerin is an inflammatory adipokine positively associated with hypertension and
      obesity. The majority of chemerin derives from the liver and adipose tissue,
      however, their individual contributions to blood pressure are unknown. We began
      studying chemerin in the normal rat using antisense oligonucleotides (ASO) with
      whole-body activity (Gen 2.5 chemerin ASO) or liver-restricted activity (GalNAc
      chemerin ASO). We hypothesized that in normotensive male Sprague-Dawley rats,
      circulating chemerin is predominately liver-derived and regulates blood pressure.
      A dosing study of the Gen 2.5 chemerin ASO (with a scrambled control ASO)
      supported 25 mg/kg as the appropriate dose. GalNAc chemerin ASO was also assessed
      and used at 10 mg/kg. Radiotelemetry monitored mean arterial pressure (MAP) for a
      1-week baseline and weekly subcutaneous ASO injections for 4 weeks. Two days
      after the final injection, animals were euthanized for tissue reverse
      transcription-polymerase chain reaction and chemerin Western analysis. Gen 2.5
      chemerin ASO treatments reduced chemerin mRNA and protein in liver,
      retroperitoneal fat (RP), and mesenteric perivascular adipose tissue (mPVAT), as
      well as reducing protein in plasma. GalNAc chemerin ASO treatments reduced
      chemerin mRNA and protein in liver and chemerin protein in plasma but had no
      effect on expression in RP fat or mPVAT. Gen 2.5 chemerin ASO treatment reduced
      MAP compared with control ASO but was unchanged in animals receiving the GalNAc
      chemerin ASO. Although circulating chemerin is liver-derived, it does not play a
      major role in blood pressure regulation. Local effects of chemerin from fat may
      explain this discrepancy and support chemerin's association with hypertension and
      obesity.

PMID- 29467311
TI  - Epstein-Barr Virus Nuclear Antigen Leader Protein Coactivates EP300.
AB  - Epstein-Barr virus nuclear antigen (EBNA) leader protein (EBNALP) is one of the
      first viral genes expressed upon B-cell infection. EBNALP is essential for EBV
      mediated B-cell immortalization. EBNALP is thought to function primarily by
      coactivating EBNA2-mediated transcription. Chromatin immune precipitation
      followed by deep sequencing (ChIP-seq) studies highlight that EBNALP frequently
      cooccupies DNA sites with host cell transcription factors (TFs), in particular,
      EP300, implicating a broader role in transcription regulation. In this study, we
      investigated the mechanisms of EBNALP transcription coactivation through EP300.
      EBNALP greatly enhanced EP300 transcription activation when EP300 was tethered to
      a promoter. EBNALP coimmunoprecipitated endogenous EP300 from lymphoblastoid cell
      lines (LCLs). EBNALP W repeat serine residues 34, 36, and 63 were required for
      EP300 association and coactivation. Deletion of the EP300 histone
      acetyltransferase (HAT) domain greatly reduced EBNALP coactivation and abolished
      the EBNALP association. An EP300 bromodomain inhibitor also abolished EBNALP
      coactivation and blocked the EP300 association with EBNALP. EBNALP sites
      cooccupied by EP300 had significantly higher ChIP-seq signals for sequence
      specific TFs, including SPI1, RelA, EBF1, IRF4, BATF, and PAX5. EBNALP- and EP300
      cooccurring sites also had much higher H3K4me1 and H3K27ac signals, indicative of
      activated enhancers. EBNALP-only sites had much higher signals for DNA looping
      factors, including CTCF and RAD21. EBNALP coactivated reporters under the control
      of NF-kappaB or SPI1. EP300 inhibition abolished EBNALP coactivation of these
      reporters. Clustered regularly interspaced short palindromic repeat interference
      targeting of EBNALP enhancer sites significantly reduced target gene expression,
      including that of EP300 itself. These data suggest a previously unrecognized
      mechanism by which EBNALP coactivates transcription through subverting of EP300
      and thus affects the expression of LCL genes regulated by a broad range of host
      TFs.IMPORTANCE Epstein-Barr virus was the first human DNA tumor virus discovered
      over 50 years ago. EBV is causally linked to ~200,000 human malignancies
      annually. These cancers include endemic Burkitt lymphoma, Hodgkin lymphoma,
      lymphoma/lymphoproliferative disease in transplant recipients or HIV-infected
      people, nasopharyngeal carcinoma, and ~10% of gastric carcinoma cases. EBV
      immortalized human B cells faithfully model key aspects of EBV
      lymphoproliferative diseases and are useful models of EBV oncogenesis. EBNALP is
      essential for EBV to transform B cells and transcriptionally coactivates EBNA2 by
      removing repressors from EBNA2-bound DNA sites. Here, we found that EBNALP can
      also modulate the activity of the key transcription activator EP300, an
      acetyltransferase that activates a broad range of transcription factors. Our data
      suggest that EBNALP regulates a much broader range of host genes than was
      previously appreciated. A small-molecule inhibitor of EP300 abolished EBNALP
      coactivation of multiple target genes. These findings suggest novel therapeutic
      approaches to control EBV-associated lymphoproliferative diseases.

PMID- 29467312
TI  - Fibronectin Facilitates Enterovirus 71 Infection by Mediating Viral Entry.
AB  - Fibronectin (FN) is a high-molecular-weight extracellular matrix protein that
      contains the RGDS motif, which is required to bind to integrins. Synthetic RGDS
      peptides have been reported to compete with FN to bind to the cell surface and
      inhibit the function of FN. Here, we identified that synthetic RGDS peptides
      significantly inhibit human enterovirus 71 (EV71) infection in cell cultures. In
      addition, mice treated with RGDS peptides and infected with EV71 had a
      significantly higher survival rate and a lower viral load than the control group.
      Because RGDS peptides affect the function of FN, we questioned whether FN may
      play a role in virus infection. Our study indicates that overexpression of FN
      enhanced EV71 infection. In contrast, knockout of FN significantly reduced viral
      yield and decreased the viral binding to host cells. Furthermore, EV71 entry,
      rather than intracellular viral replication, was blocked by FN inhibitor
      pretreatment. Next, we found that FN could interact with the EV71 capsid protein
      VP1, and further truncated-mutation assays indicated that the D2 domain of FN
      could interact with the N-terminal fragment of VP1. Taken together, our results
      demonstrate that the host factor FN binds to EV71 particles and facilitates EV71
      entry, providing a potential therapy target for EV71 infection.IMPORTANCE Hand,
      foot, and mouth disease outbreaks have occurred frequently in recent years,
      sometimes causing severe neurological complications and even death in infants and
      young children worldwide. Unfortunately, no effective antiviral drugs are
      available for human enterovirus 71 (EV71), one of the viruses that cause hand,
      foot, and mouth disease. The infection process and the host factors involved
      remain unknown, although several receptors have been identified. In this study,
      we found that the host factor fibronectin (FN) facilitated EV71 replication by
      interacting with EV71 particles and further mediated their entry. The RGDS
      peptide, an FN inhibitor, significantly inhibited EV71 replication in both RD
      cells and mice. In conclusion, our research identified a new host factor involved
      in EV71 infection, providing a new potential antiviral target for EV71 treatment.

PMID- 29467313
TI  - Reduced Chronic Lymphocyte Activation following Interferon Alpha Blockade during
      the Acute Phase of Simian Immunodeficiency Virus Infection in Rhesus Macaques.
AB  - Pathogenic human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV)
      infection of humans and rhesus macaques (RMs) induces persistently high
      production of type I interferon (IFN-I), which is thought to contribute to
      disease progression. To elucidate the specific role of interferon alpha (IFN
      alpha) in SIV pathogenesis, 12 RMs were treated prior to intravenous (i.v.)
      SIVmac239 infection with a high or a low dose of an antibody (AGS-009) that
      neutralizes most IFN-alpha subtypes and were compared with six mock-infused, SIV
      infected controls. Plasma viremia was measured postinfection to assess the effect
      of IFN-alpha blockade on virus replication, and peripheral blood and lymphoid
      tissue samples were analyzed by immunophenotypic staining. Consistent with the
      known antiviral effect of IFN-I, high-dose AGS-009 treatment induced a modest
      increase in acute-phase viral loads versus controls. Four out of 6 RMs receiving
      a high dose of AGS-009 also experienced an early decline in CD4+ T cell counts
      that was associated with progression to AIDS. Interestingly, 50% of the animals
      treated with AGS-009 (6/12) developed AIDS within 1 year of infection compared
      with 17% (1/6) of untreated controls. Finally, blockade of IFN-alpha decreased
      the levels of activated CD4+ and CD8+ T cells, as well as B cells, as measured by
      PD-1 and/or Ki67 expression. The lower levels of activated lymphocytes in IFN
      alpha-blockaded animals supports the hypothesis that IFN-alpha signaling
      contributes to lymphocyte activation during SIV infection and suggests that this
      signaling pathway is involved in controlling virus replication during acute
      infection. The potential anti-inflammatory effect of IFN-alpha blockade should be
      explored as a strategy to reduce immune activation in HIV-infected
      individuals.IMPORTANCE Interferon alpha (IFN-alpha) is a member of a family of
      molecules (type I interferons) that prevent or limit virus infections in mammals.
      However, IFN-alpha production may contribute to the chronic immune activation
      that is thought to be the primary cause of immune decline and AIDS in HIV
      infected patients. The study presented here attempts to understand the
      contribution of IFN-alpha to the natural history and progression of SIV infection
      of rhesus macaques, the primary nonhuman primate model system for testing
      hypotheses about HIV infection in humans. Here, we show that blockade of IFN
      alpha action promotes lower chronic immune activation but higher early viral
      loads, with a trend toward faster disease progression. This study has significant
      implications for new treatments designed to impact the type I interferon system.

PMID- 29467314
TI  - A prominent role of the human cytomegalovirus UL8 glycoprotein restraining pro
      inflammatory cytokine production by myeloid cells at late times during infection.
AB  - Human cytomegalovirus (HCMV) persistence in infected individuals relies on a
      plethora of mechanisms to efficiently reduce host immune responses. To that end,
      HCMV commits a variety of gene products, some of which have not been identified
      yet. Here we characterized the UL8 gene, which consists of two exons, sharing the
      first with the HCMV RL11 family member UL7 UL8 is a transmembrane protein with an
      N-terminal immunoglobulin (Ig)-like domain in common with UL7 but with an
      extended stalk and a distinctive cytoplasmic tail. The UL8 open reading frame
      gives rise to a heavily glycosylated protein, predominantly expressed on the cell
      surface, from where it can be partially endocytosed and subsequently degraded.
      Infections with UL8-tagged viruses indicated that UL8 was synthesized with late
      phase kinetics. By virtue of its highly conserved Ig-like domain, this viral
      protein interacted with a surface molecule present on activated neutrophils.
      Notably, when ectopically expressed in THP-1 myeloid cells, UL8 was able to
      significantly reduce the production of a variety of pro-inflammatory cytokines.
      Mutations in UL8 indicated that this functional effect was mediated by the cell
      surface expression of its Ig-like domain. To investigate the impact of the viral
      protein in the infection context, we engineered HCMVs lacking the UL8 gene, and
      demonstrated that UL8 decreases the release of a large number of pro-inflammatory
      factors at late times after infection of THP-1 cells. Our data indicate that UL8
      may exert an immunosuppressive role key for HCMV survival in the host.IMPORTANCE
      Human cytomegalovirus (HCMV) is a major pathogen that causes life-threatening
      diseases and disabilities in infected newborns and immunocompromised individuals.
      Containing one of the largest genomes among all reported human viruses, HCMV
      encodes an impressive repertoire of gene products. However, the functions of a
      large proportion of them remain still unknown, a fact that complicates the design
      of new therapeutic approaches to prevent or treat HCMV associated diseases. In
      this report, we have conducted an extensive study of UL8, one of the previously
      uncharacterized HCMV open reading frames. We found that the UL8 protein is
      expressed at late times post infection and utilized by HCMV to reduce the
      production of pro-inflammatory factors by infected myeloid cells. Thus, the work
      presented here points to a key role of UL8 as a novel HCMV immune modulator
      capable to restrain host antiviral defenses.

PMID- 29467315
TI  - Plasmid Partitioning by Human Tumor Viruses.
AB  - The human tumor viruses that replicate as plasmids (we use the term plasmid to
      avoid any confusion in the term episome, which was coined to mean DNA elements
      that occur both extrachromosomally and as integrated forms during their life
      cycles, as does phage lambda) share many features in their DNA synthesis. We know
      less about their mechanisms of maintenance in proliferating cells, but these
      mechanisms must underlie their partitioning to daughter cells. One amazing
      implication of how these viruses are thought to maintain themselves is that while
      host chromosomes commit themselves to partitioning in mitosis, these tumor
      viruses would commit themselves to partitioning before mitosis and probably in S
      phase shortly after their synthesis.

PMID- 29467316
TI  - Formation of RNA Granule-Derived Capsid Assembly Intermediates Appears To Be
      Conserved between Human Immunodeficiency Virus Type 1 and the Nonprimate
      Lentivirus Feline Immunodeficiency Virus.
AB  - During immature capsid assembly in cells, human immunodeficiency virus type 1
      (HIV-1) Gag co-opts a host RNA granule, forming a pathway of intracellular
      assembly intermediates containing host components, including two cellular
      facilitators of assembly, ABCE1 and DDX6. A similar assembly pathway has been
      observed for other primate lentiviruses. Here we asked whether feline
      immunodeficiency virus (FIV), a nonprimate lentivirus, also forms RNA granule
      derived capsid assembly intermediates. First, we showed that the released FIV
      immature capsid and a large FIV Gag-containing intracellular complex are unstable
      during analysis, unlike for HIV-1. We identified harvest conditions, including in
      situ cross-linking, that overcame this problem, revealing a series of FIV Gag
      containing complexes corresponding in size to HIV-1 assembly intermediates.
      Previously, we showed that assembly-defective HIV-1 Gag mutants are arrested at
      specific assembly intermediates; here we identified four assembly-defective FIV
      Gag mutants, including three not previously studied, and demonstrated that they
      appear to be arrested at the same intermediate as the cognate HIV-1 mutants.
      Further evidence that these FIV Gag-containing complexes correspond to assembly
      intermediates came from coimmunoprecipitations demonstrating that endogenous
      ABCE1 and the RNA granule protein DDX6 are associated with FIV Gag, as shown
      previously for HIV-1 Gag, but are not associated with a ribosomal protein, at
      steady state. Additionally, we showed that FIV Gag associates with another RNA
      granule protein, DCP2. Finally, we validated the FIV Gag-ABCE1 and FIV Gag-DCP2
      interactions with proximity ligation assays demonstrating colocalization in situ
      Together, these data support a model in which primate and nonprimate lentiviruses
      form intracellular capsid assembly intermediates derived from nontranslating host
      RNA granules.IMPORTANCE Like HIV-1 Gag, FIV Gag assembles into immature capsids;
      however, it is not known whether FIV Gag progresses through a pathway of immature
      capsid assembly intermediates derived from host RNA granules, as shown for HIV-1
      Gag. Here we showed that FIV Gag forms complexes that resemble HIV-1 capsid
      assembly intermediates in size and in their association with ABCE1 and DDX6, two
      host facilitators of HIV-1 immature capsid assembly that are found in HIV-1
      assembly intermediates. Our studies also showed that known and novel assembly
      defective FIV Gag mutants fail to progress past putative intermediates in a
      pattern resembling that observed for HIV-1 Gag mutants. Finally, we used imaging
      to demonstrate colocalization of FIV Gag with ABCE1 and with the RNA granule
      protein DCP2. Thus, we conclude that formation of assembly intermediates derived
      from host RNA granules is likely conserved between primate and nonprimate
      lentiviruses and could provide targets for future antiviral strategies.

PMID- 29467318
TI  - Adenovirus infection of human enteroids reveals interferon sensitivity and
      preferential infection of goblet cells.
AB  - Human adenoviruses (HAdV) are significant human pathogens. Although only a subset
      of HAdV serotypes commonly cause gastroenteritis in humans, most HAdV species
      replicate in the gastrointestinal tract. Knowledge of the complex interaction
      between HAdVs and the human intestinal epithelium has been limited by the lack of
      a suitable cell culture system containing relevant cell types. Recently, this
      need has been met by the stable and prolonged cultivation of primary intestinal
      epithelial cells as enteroids. Human enteroids have been used to reveal novel and
      interesting aspects of rotavirus, norovirus, and enterovirus replication,
      prompting us to explore their suitability for HAdV culture. We found that both
      prototype strains and clinical isolates of enteric and non-enteric HAdVs
      productively replicate in human enteroids. HAdV-5p, a respiratory pathogen, and
      HAdV-41p, an enteric pathogen, are both sensitive to type I and III interferons
      in human enteroid monolayers but not A549 cells. Interestingly, HAdV-5p, but not
      HAdV-41p, preferentially infected goblet cells. And, HAdV-5p but not HAdV-41p was
      potently neutralized by the enteric human alpha-defensin HD5. These studies
      highlight new facets of HAdV biology that are uniquely revealed by primary
      intestinal epithelial cell culture.IMPORTANCE Enteric adenoviruses are a
      significant cause of childhood gastroenteritis worldwide, yet our understanding
      of their unique biology is limited. Here we report robust replication of both
      prototype and clinical isolates of enteric and respiratory human adenoviruses in
      enteroids, a primary intestinal cell culture system. Recent studies have shown
      that other fastidious enteric viruses replicate in human enteroids. Therefore,
      human enteroids may provide a unified platform for culturing enteric viruses,
      potentially enabling isolation of a greater diversity of viruses from patients.
      Moreover, both the ability of interferon to restrict respiratory and enteric
      adenoviruses and a surprising preference of a respiratory serotype for goblet
      cells demonstrates the power of this culture system to uncover aspects of
      adenovirus biology that were previously unattainable with standard cell lines.

PMID- 29467317
TI  - Bovine Nebovirus Interacts with a Wide Spectrum of Histo-Blood Group Antigens.
AB  - Some viruses within the Caliciviridae family initiate their replication cycle by
      attachment to cell surface carbohydrate moieties, histo-blood group antigens
      (HBGAs), and/or terminal sialic acids (SAs). Although bovine nebovirus (BNeV),
      one of the enteric caliciviruses, is an important causative agent of acute
      gastroenteritis in cattle, its attachment factors and possibly other cellular
      receptors remain unknown. Using a comprehensive series of protein-ligand
      biochemical assays, we sought to determine whether BNeV recognizes cell surface
      HBGAs and/or SAs as attachment factors. It was found that BNeV virus-like
      particles (VLPs) bound to A type/H type 2/Ley HBGAs expressed in the bovine
      digestive tract and are related to HBGAs expressed in humans and other host
      species, suggesting a wide spectrum of HBGA recognition by BNeV. BNeV VLPs also
      bound to a large variety of different bovine and human saliva samples of all ABH
      and Lewis types, supporting previously obtained results and suggesting a zoonotic
      potential of BNeV transmission. Removal of alpha1,2-linked fucose and alpha1,3/4
      linked fucose epitopes of target HBGAs by confirmation-specific enzymes reduced
      the binding of BNeV VLPs to synthetic HBGAs, bovine and human saliva, cultured
      cell lines, and bovine small intestine mucosa, further supporting a wide HBGA
      binding spectrum of BNeV through recognition of alpha1,2-linked fucose and
      alpha1,3/4-linked fucose epitopes of targeted HBGAs. However, removal of terminal
      alpha2,3- and alpha2,6-linked SAs by their specific enzyme had no inhibitory
      effects on binding of BNeV VLPs, indicating that BNeV does not use terminal SAs
      as attachment factors. Further details of the binding specificity of BNeV remain
      to be explored.IMPORTANCE Enteric caliciviruses such as noroviruses, sapoviruses,
      and recoviruses are the most important etiological agents of severe acute
      gastroenteritis in humans and many other mammalian host species. They initiate
      infection by attachment to cell surface carbohydrate moieties, HBGAs, and/or
      terminal SAs. However, the attachment factor(s) for BNeV, a recently classified
      enteric calicivirus genus/type species, remains unexplored. Here, we demonstrate
      that BNeV VLPs have a wide spectrum of binding to synthetic HBGAs, bovine and
      human saliva samples, and bovine duodenal sections. We further discovered that
      alpha1,2-linked fucose and alpha1,3/4-linked fucose epitopes are essential for
      binding of BNeV VLPs. However, BNeV VLPs do not bind to terminal SAs on cell
      carbohydrates. Continued investigation regarding the proteinaceous receptor(s)
      will be necessary for better understanding of the tropism, pathogenesis, and host
      range of this important viral genus.

PMID- 29467320
TI  - Whatever happened to silence?

PMID- 29467319
TI  - Escape of Hepatitis C Virus from Epitope I Neutralization Increases Sensitivity
      of Other Neutralization Epitopes.
AB  - The hepatitis C virus (HCV) E2 glycoprotein is a major target of the neutralizing
      antibody (nAb) response, with multiple type-specific and broadly neutralizing
      antibody (bnAb) epitopes identified. The 412-to-423 region can generate bnAbs
      that block interaction with the cell surface receptor CD81, with activity toward
      multiple HCV genotypes. In this study, we reveal the structure of rodent
      monoclonal antibody 24 (MAb24) with an extensive contact area toward a peptide
      spanning the 412-to-423 region. The crystal structure of the MAb24-peptide 412-to
      423 complex reveals the paratope bound to a peptide hairpin highly similar to
      that observed with human MAb HCV1 and rodent MAb AP33, but with a different angle
      of approach. In viral outgrowth experiments, we demonstrated three distinct
      genotype 2a viral populations that acquired resistance to MAb24 via N415D, N417S,
      and N415D/H386R mutations. Importantly, the MAb24-resistant viruses exhibited
      significant increases in sensitivity to the majority of bnAbs directed to
      epitopes within the 412-to-423 region and in additional antigenic determinants
      located within E2 and the E1E2 complex. This study suggests that modification of
      N415 causes a global change in glycoprotein structure that increases its
      vulnerability to neutralization by other antibodies. This finding suggests that
      in the context of an antibody response to viral infection, acquisition of escape
      mutations in the 412-to-423 region renders the virus more susceptible to
      neutralization by other specificities of nAbs, effectively reducing the
      immunological fitness of the virus. A vaccine for HCV that generates polyspecific
      humoral immunity with specificity for the 412-to-423 region and at least one
      other region of E2 is desirable.IMPORTANCE Understanding how antibodies
      neutralize hepatitis C virus (HCV) is essential for vaccine development. This
      study reveals for the first time that when HCV develops resistance to a major
      class of bnAbs targeting the 412-to-423 region of E2, this results in a
      concomitant increase in sensitivity to neutralization by a majority of other bnAb
      specificities. Vaccines for the prevention of HCV infection should therefore
      generate bnAbs directed toward the 412-to-423 region of E2 and additional bnAb
      epitopes within the viral glycoproteins.

PMID- 29467321
TI  - Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with
      advanced solid tumors.
AB  - BACKGROUND: Constitutive activation of ERK1/2 occurs in various cancers, and its
      reactivation is a well-described resistance mechanism to MAPK inhibitors. ERK
      inhibitors may overcome the limitations of MAPK inhibitor blockade. The dual
      mechanism inhibitor SCH772984 has shown promising preclinical activity across
      various BRAFV600/RAS-mutant cancer cell lines and human cancer xenografts.
      METHODS: We have developed an orally bioavailable ERK inhibitor, MK-8353;
      conducted preclinical studies to demonstrate activity, pharmacodynamic endpoints,
      dosing, and schedule; completed a study in healthy volunteers (P07652); and
      subsequently performed a phase I clinical trial in patients with advanced solid
      tumors (MK-8353-001). In the P07652 study, MK-8353 was administered as a single
      dose in 10- to 400-mg dose cohorts, whereas in the MK-8353-001 study, MK-8353 was
      administered in 100- to 800-mg dose cohorts orally twice daily. Safety,
      tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity were
      analyzed. RESULTS: MK-8353 exhibited comparable potency with SCH772984 across
      various preclinical cancer models. Forty-eight patients were enrolled in the
      P07652 study, and twenty-six patients were enrolled in the MK-8353-001 study.
      Adverse events included diarrhea (44%), fatigue (40%), nausea (32%), and rash
      (28%). Dose-limiting toxicity was observed in the 400-mg and 800-mg dose cohorts.
      Sufficient exposure to MK-8353 was noted that correlated with biological activity
      in preclinical data. Three of fifteen patients evaluable for treatment response
      in the MK-8353-001 study had partial response, all with BRAFV600-mutant
      melanomas. CONCLUSION: MK-8353 was well tolerated up to 400 mg twice daily and
      exhibited antitumor activity in patients with BRAFV600-mutant melanoma. However,
      antitumor activity was not particularly correlated with pharmacodynamic
      parameters. TRIAL REGISTRATION: ClinicalTrials.gov NCT01358331. FUNDING: Merck
      Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., and NIH (P01 CA168585 and
      R35 CA197633).

PMID- 29467322
TI  - Gut microbiota modulates adoptive cell therapy via CD8alpha dendritic cells and
      IL-12.
AB  - Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here,
      we report that adoptive T cell efficacy in tumor-bearing mice is significantly
      affected by differences in the native composition of the gut microbiome or
      treatment with antibiotics, or by heterologous fecal transfer. Depletion of
      bacteria with vancomycin decreased the rate of tumor growth in mice from The
      Jackson Laboratory receiving ACT, whereas treatment with neomycin and
      metronidazole had no effect, indicating the role of specific bacteria in host
      response. Vancomycin treatment induced an increase in systemic CD8alpha+ DCs,
      which sustained systemic adoptively transferred antitumor T cells in an IL-12
      dependent manner. In subjects undergoing allogeneic hematopoietic cell
      transplantation, we found that oral vancomycin also increased IL-12 levels.
      Collectively, our findings demonstrate an important role played by the gut
      microbiota in the antitumor effectiveness of ACT and suggest potentially new
      avenues to improve response to ACT by altering the gut microbiota.

PMID- 29467323
TI  - Von Hippel-Lindau mutations disrupt vascular patterning and maturation via Notch.
AB  - Von Hippel-Lindau (VHL) gene mutations induce neural tissue hemangioblastomas, as
      well as highly vascularized clear cell renal cell carcinomas (ccRCCs).
      Pathological vessel remodeling arises from misregulation of HIFs and VEGF, among
      other genes. Variation in disease penetrance has long been recognized in relation
      to genotype. We show Vhl mutations also disrupt Notch signaling, causing mutation
      specific vascular abnormalities, e.g., type 1 (null) vs. type 2B (murine G518A
      representing human R167Q). In conditional mutation retina vasculature, Vhl-null
      mutation (i.e., UBCCreER/+Vhlfl/fl) had little effect on initial vessel
      branching, but it severely reduced arterial and venous branching at later stages.
      Interestingly, this mutation accelerated arterial maturation, as observed in
      retina vessel morphology and aberrant alpha-smooth muscle actin localization,
      particularly in vascular pericytes. RNA sequencing analysis identified gene
      expression changes within several key pathways, including Notch and smooth muscle
      cell contractility. Notch inhibition failed to reverse later-stage branching
      defects but rescued the accelerated arterialization. Retinal vessels harboring
      the type 2B Vhl mutation (i.e., UBCCreER/+Vhlfl/2B) displayed stage-specific
      changes in vessel branching and an advanced progression toward an arterial
      phenotype. Disrupting Notch signaling in type 2B mutants increased both artery
      and vein branching and restored arterial maturation toward nonmutant levels. By
      revealing differential effects of the null and type 2B Vhl mutations on vessel
      branching and maturation, these data may provide insight into the variability of
      VHL-associated vascular changes - particularly the heterogeneity and
      aggressiveness in ccRCC vessel growth - and also suggest Notch pathway targets
      for treating VHL syndrome.

PMID- 29467324
TI  - Angiokine Wisp-1 is increased in myocardial infarction and regulates cardiac
      endothelial signaling.
AB  - Myocardial infarctions (MIs) cause the loss of myocytes due to lack of sufficient
      oxygenation and latent revascularization. Although the administration of histone
      deacetylase (HDAC) inhibitors reduces the size of infarctions and improves
      cardiac physiology in small-animal models of MI injury, the cellular targets of
      the HDACs, which the drugs inhibit, are largely unspecified. Here, we show that
      WNT-inducible secreted protein-1 (Wisp-1), a matricellular protein that promotes
      angiogenesis in cancers as well as cell survival in isolated cardiac myocytes and
      neurons, is a target of HDACs. Further, Wisp-1 transcription is regulated by
      HDACs and can be modified by the HDAC inhibitor, suberanilohydroxamic acid
      (SAHA/vorinostat), after MI injury. We observe that, at 7 days after MI, Wisp-1
      is elevated 3-fold greater in the border zone of infarction in mice that
      experience an MI injury and are injected daily with SAHA, relative to MI alone.
      Additionally, human coronary artery endothelial cells (HCAECs) produce WISP-1 and
      are responsive to autocrine WISP-1-mediated signaling, which functionally
      promotes their proangiogenic behavior. Altering endogenous expression of WISP-1
      in HCAECs directly impacts their network density in vitro. Therapeutic
      interventions after a heart attack define the extent of infarct injury, cell
      survival, and overall prognosis. Our studies shown here identify a potentially
      novel cardiac angiokine, Wisp-1, that may contribute to beneficial post-MI
      treatment modalities.

PMID- 29467325
TI  - Lipid abnormalities in atopic skin are driven by type 2 cytokines.
AB  - Lipids in the stratum corneum of atopic dermatitis (AD) patients differ
      substantially in composition from healthy subjects. We hypothesized that
      hyperactivated type 2 immune response alters AD skin lipid metabolism. We have
      analyzed stratum corneum lipids from nonlesional and lesional skin of AD subjects
      and IL-13 skin-specific Tg mice. We also directly examined the effects of IL-4/IL
      13 on human keratinocytes in vitro. Mass spectrometric analysis of lesional
      stratum corneum from AD subjects and IL-13 Tg mice revealed an increased
      proportion of short-chain (N-14:0 to N-24:0) NS ceramides, sphingomyelins, and
      14:0-22:0 lysophosphatidylcholines (14:0-22:0 LPC) with a simultaneous decline in
      the proportion of corresponding long-chain species (N-26:0 to N-32:0
      sphingolipids and 24:0-30:0 LPC) when compared with healthy controls. An increase
      in short-chain LPC species was also observed in nonlesional AD skin. Similar
      changes were observed in IL-4/IL-13-driven responses in Ca2+-differentiated human
      keratinocytes in vitro, all being blocked by STAT6 silencing with siRNA. RNA
      sequencing analysis performed on stratum corneum of AD as compared with healthy
      subjects identified decreased expression of fatty acid elongases ELOVL3 and
      ELOVL6 that contributed to observed changes in atopic skin lipids. IL-4/IL-13
      also inhibited ELOVL3 and ELOVL6 expression in keratinocyte cultures in a STAT6
      dependent manner. Downregulation of ELOVL3/ELOVL6 expression in keratinocytes by
      siRNA decreased the proportion of long-chain fatty acids globally and in
      sphingolipids. Thus, our data strongly support the pathogenic role of type 2
      immune activation in AD skin lipid metabolism.

PMID- 29467327
TI  - Talking TOR: a conversation with Joe Heitman and Rao Movva.

PMID- 29467326
TI  - Loss of epigenetic regulator TET2 and oncogenic KIT regulate myeloid cell
      transformation via PI3K pathway.
AB  - Mutations in KIT and TET2 are associated with myeloid malignancies. We show that
      loss of TET2-induced PI3K activation and -increased proliferation is rescued by
      targeting the p110alpha/delta subunits of PI3K. RNA-Seq revealed a hyperactive c
      Myc signature in Tet2-/- cells, which is normalized by inhibiting PI3K signaling.
      Loss of TET2 impairs the maturation of myeloid lineage-derived mast cells by
      dysregulating the expression of Mitf and Cebpa, which is restored by low-dose
      ascorbic acid and 5-azacytidine. Utilizing a mouse model in which the loss of
      TET2 precedes the expression of oncogenic Kit, similar to the human disease,
      results in the development of a non-mast cell lineage neoplasm (AHNMD), which is
      responsive to PI3K inhibition. Thus, therapeutic approaches involving
      hypomethylating agents, ascorbic acid, and isoform-specific PI3K inhibitors are
      likely to be useful for treating patients with TET2 and KIT mutations.

PMID- 29467328
TI  - Allograft dendritic cell p40 homodimers activate donor-reactive memory CD8+ T
      cells.
AB  - Recipient endogenous memory T cells with donor reactivity pose an important
      barrier to successful transplantation and costimulatory blockade-induced graft
      tolerance. Longer ischemic storage times prior to organ transplantation increase
      early posttransplant inflammation and negatively impact early graft function and
      long-term graft outcome. Little is known about the mechanisms enhancing
      endogenous memory T cell activation to mediate tissue injury within the increased
      inflammatory environment of allografts subjected to prolonged cold ischemic
      storage (CIS). Endogenous memory CD4+ and CD8+ T cell activation is markedly
      increased within complete MHC-mismatched cardiac allografts subjected to
      prolonged versus minimal CIS, and the memory CD8+ T cells directly mediate CTLA
      4Ig-resistant allograft rejection. Memory CD8+ T cell activation within
      allografts subjected to prolonged CIS requires memory CD4+ T cell stimulation of
      graft DCs to produce p40 homodimers, but not IL-12 p40/p35 heterodimers.
      Targeting p40 abrogates memory CD8+ T cell proliferation within the allografts
      and their ability to mediate CTLA-4Ig-resistant allograft rejection. These
      findings indicate a critical role for memory CD4+ T cell-graft DC interactions to
      increase the intensity of endogenous memory CD8+ T cell activation needed to
      mediate rejection of higher-risk allografts subjected to increased CIS.

PMID- 29467329
TI  - T cell developmental arrest in former premature infants increases risk of
      respiratory morbidity later in infancy.
AB  - The inverse relationship between gestational age at birth and postviral
      respiratory morbidity suggests that infants born preterm (PT) may miss a critical
      developmental window of T cell maturation. Despite a continued increase in
      younger PT survivors with respiratory complications, we have limited
      understanding of normal human fetal T cell maturation, how ex utero development
      in premature infants may interrupt normal T cell development, and whether T cell
      development has an effect on infant outcomes. In our longitudinal cohort of 157
      infants born between 23 and 42 weeks of gestation, we identified differences in T
      cells present at birth that were dependent on gestational age and differences in
      postnatal T cell development that predicted respiratory outcome at 1 year of age.
      We show that naive CD4+ T cells shift from a CD31-TNF-alpha+ bias in mid
      gestation to a CD31+IL-8+ predominance by term gestation. Former PT infants
      discharged with CD31+IL8+CD4+ T cells below a range similar to that of full-term
      born infants were at an over 3.5-fold higher risk for respiratory complications
      after NICU discharge. This study is the first to our knowledge to identify a
      pattern of normal functional T cell development in later gestation and to
      associate abnormal T cell development with health outcomes in infants.

PMID- 29467330
TI  - Inducible podocyte-specific deletion of CTCF drives progressive kidney disease
      and bone abnormalities.
AB  - Progressive chronic kidney diseases (CKDs) are on the rise worldwide. However,
      the sequence of events resulting in CKD progression remain poorly understood.
      Animal models of CKD exploring these issues are confounded by systemic toxicities
      or surgical interventions to acutely induce kidney injury. Here we report the
      generation of a CKD mouse model through the inducible podocyte-specific ablation
      of an essential endogenous molecule, the chromatin structure regulator CCCTC
      binding factor (CTCF), which leads to rapid podocyte loss (iCTCFpod-/-). As a
      consequence, iCTCFpod-/- mice develop severe progressive albuminuria,
      hyperlipidemia, hypoalbuminemia, and impairment of renal function, and die within
      8-10 weeks. CKD progression in iCTCFpod-/- mice leads to high serum phosphate and
      elevations in fibroblast growth factor 23 (FGF23) and parathyroid hormone that
      rapidly cause bone mineralization defects, increased bone resorption, and bone
      loss. Dissection of the timeline leading to glomerular pathology in this CKD
      model led to the surprising observation that podocyte ablation and the resulting
      glomerular filter destruction is sufficient to drive progressive CKD and
      osteodystrophy in the absence of interstitial fibrosis. This work introduces an
      animal model with significant advantages for the study of CKD progression, and it
      highlights the need for podocyte-protective strategies for future kidney
      therapeutics.

PMID- 29467331
TI  - PTEN deficiency promotes pathological vascular remodeling of human coronary
      arteries.
AB  - Phosphatase and tensin homolog (PTEN) is an essential regulator of the
      differentiated vascular smooth muscle cell (SMC) phenotype. Our goal was to
      establish that PTEN loss promotes SMC dedifferentiation and pathological vascular
      remodeling in human atherosclerotic coronary arteries and nonatherosclerotic
      coronary arteries exposed to continuous-flow left ventricular assist devices (CF
      LVADs). Arteries were categorized as nonatherosclerotic hyperplasia (NAH),
      atherosclerotic hyperplasia (AH), or complex plaque (CP). NAH coronary arteries
      from CF-LVAD patients were compared to NAH coronaries from non-LVAD patients.
      Intimal PTEN and SMC contractile protein expression was reduced compared with the
      media in arteries with NAH, AH, or CP. Compared with NAH, PTEN and SMC
      contractile protein expression was reduced in the media and intima of arteries
      with AH and CP. NAH arteries from CF-LVAD patients showed marked vascular
      remodeling and reduced PTEN and alpha-smooth muscle actin (alphaSMA) in medial
      SMCs compared with arteries from non-LVAD patients; this correlated with
      increased medial collagen deposition. Mechanistically, compared with ApoE-/-
      mice, SMC-specific PTEN-null/ApoE-/- double-knockout mice exhibited accelerated
      atherosclerosis progression and increased vascular fibrosis. By microarray and
      validated quantitative RT-PCR analysis, SMC PTEN deficiency promotes a global
      upregulation of proinflammatory and profibrotic genes. We propose that PTEN is an
      antiinflammatory, antifibrotic target that functions to maintain SMC
      differentiation. SMC loss of PTEN results in pathological vascular remodeling of
      human arteries.

PMID- 29467332
TI  - Chronic beta2AR stimulation limits CFTR activation in human airway epithelia.
AB  - Traditional pulmonary therapies for cystic fibrosis (CF) target the downstream
      effects of CF transmembrane conductance regulator (CFTR) dysfunction (the cause
      of CF). Use of one such therapy, beta-adrenergic bronchodilators (such as
      albuterol), is nearly universal for airway clearance. Conversely, novel modulator
      therapies restore function to select mutant CFTR proteins, offering a disease
      modifying treatment. Recent trials of modulators targeting F508del-CFTR, the most
      common CFTR mutation, suggest that chronic beta-agonist use may undermine
      clinical modulator benefits. We therefore sought to understand the impact of
      chronic or excess beta-agonist exposure on CFTR activation in human airway
      epithelium. The present studies demonstrate a greater than 60% reduction in both
      wild-type and modulator-corrected F508del-CFTR activation following chronic
      exposure to short- and long-acting beta-agonists. This reduction was due to
      reduced cellular generation of cAMP downstream of the beta-2 adrenergic receptor
      G protein complex. Our results point towards a posttranscriptional reduction in
      adenylyl cyclase function as the mechanism of impaired CFTR activation produced
      by prolonged beta-agonist exposure. beta-Agonist-induced CFTR dysfunction was
      sufficient to abrogate VX809/VX770 modulation of F508del-CFTR in vitro.
      Understanding the clinical relevance of our observations is critical for CF
      patients using these drugs, and for investigators to inform future CFTR modulator
      drug trials.

PMID- 29467333
TI  - CHD7 represses the retinoic acid synthesis enzyme ALDH1A3 during inner ear
      development.
AB  - CHD7, an ATP-dependent chromatin remodeler, is disrupted in CHARGE syndrome, an
      autosomal dominant disorder characterized by variably penetrant abnormalities in
      craniofacial, cardiac, and nervous system tissues. The inner ear is uniquely
      sensitive to CHD7 levels and is the most commonly affected organ in individuals
      with CHARGE. Interestingly, upregulation or downregulation of retinoic acid (RA)
      signaling during embryogenesis also leads to developmental defects similar to
      those in CHARGE syndrome, suggesting that CHD7 and RA may have common target
      genes or signaling pathways. Here, we tested three separate potential mechanisms
      for CHD7 and RA interaction: (a) direct binding of CHD7 with RA receptors, (b)
      regulation of CHD7 levels by RA, and (c) CHD7 binding and regulation of RA
      related genes. We show that CHD7 directly regulates expression of Aldh1a3, the
      gene encoding the RA synthetic enzyme ALDH1A3 and that loss of Aldh1a3 partially
      rescues Chd7 mutant mouse inner ear defects. Together, these studies indicate
      that ALDH1A3 acts with CHD7 in a common genetic pathway to regulate inner ear
      development, providing insights into how CHD7 and RA regulate gene expression and
      morphogenesis in the developing embryo.

PMID- 29467334
TI  - A specific phosphorylation regulates the protective role of alphaA-crystallin in
      diabetes.
AB  - Neurodegeneration is a central aspect of the early stages of diabetic
      retinopathy, the primary ocular complication associated with diabetes. While
      progress has been made to improve the vascular perturbations associated with
      diabetic retinopathy, there are still no treatment options to counteract the
      neuroretinal degeneration associated with diabetes. Our previous work suggested
      that the molecular chaperones alpha-crystallins could be involved in the
      pathophysiology of diabetic retinopathy; however, the role and regulation of
      alpha-crystallins remained unknown. In the present study, we demonstrated the
      neuroprotective role of alphaA-crystallin during diabetes and its regulation by
      its phosphorylation on residue 148. We further characterized the dual role of
      alphaA-crystallin in neurons and glia, its essential role for neuronal survival,
      and its direct dependence on phosphorylation on this residue. These findings
      support further evaluation of alphaA-crystallin as a treatment option to promote
      neuron survival in diabetic retinopathy and neurodegenerative diseases in
      general.

PMID- 29467335
TI  - Apolipoproteins E and CIII interact to regulate HDL metabolism and coronary heart
      disease risk.
AB  - BACKGROUND: Subspecies of HDL contain apolipoprotein E (apoE) and/or apoCIII.
      Both proteins have properties that could affect HDL metabolism. The relation
      between HDL metabolism and risk of coronary heart disease (CHD) is not well
      understood. METHODS: Eighteen participants were given a bolus infusion of [D3]L
      leucine to label endogenous proteins on HDL. HDL was separated into subspecies
      containing apoE and/or apoCIII and then into 4 sizes. Metabolic rates for apoA-I
      in HDL subspecies and sizes were determined by interactive modeling. The
      concentrations of apoE in HDL that contain or lack apoCIII were measured in a
      prospective study in Denmark including 1,949 incident CHD cases during 9 years.
      RESULTS: HDL containing apoE but not apoCIII is disproportionately secreted into
      the circulation, actively expands while circulating, and is quickly cleared.
      These are key metabolic steps in reverse cholesterol transport, which may protect
      against atherosclerosis. ApoCIII on HDL strongly attenuates these metabolic
      actions of HDL apoE. In the epidemiological study, the relation between HDL apoE
      concentration and CHD significantly differed depending on whether apoCIII was
      present. HDL apoE was associated significantly with lower risk of CHD only in the
      HDL subspecies lacking apoCIII. CONCLUSIONS: ApoE and apoCIII on HDL interact to
      affect metabolism and CHD. ApoE promotes metabolic steps in reverse cholesterol
      transport and is associated with lower risk of CHD. ApoCIII, when coexisting with
      apoE on HDL, abolishes these benefits. Therefore, differences in metabolism of
      HDL subspecies pertaining to reverse cholesterol transport are reflected in
      differences in association with CHD. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01399632. FUNDING: This work was supported by NIH grant R01HL095964 to FMS and
      by a grant to the Harvard Clinical and Translational Science Center
      (8UL1TR0001750) from the National Center for Advancing Translational Science.

PMID- 29467336
TI  - Frameshift events predict anti-PD-1/L1 response in head and neck cancer.
AB  - Programmed cell death protein 1 (PD-1) inhibitors have efficacy in treating
      squamous cell carcinoma of the head and neck (SCCHN), but objective response
      rates are low. PD-1 ligand (PD-L1) expression alone is not considered a robust
      predictor of response and additional biomarkers are needed. This 3-year
      observational cohort followed 126 SCCHN patients treated with anti-PD-1/L1
      therapy. Prior to treatment, 81 (64%) had targeted massively parallel tumor
      sequencing. Of these, 42 (52%) underwent fluorescence-activated cell sorting and
      PD-L1 immunohistochemistry for tumor immunoprofiling. Six (5%) complete responses
      (CRs) and 11 (9%) partial responses (PRs) were observed. Those treated with prior
      chemotherapy (98, 78%) versus only surgery and/or radiation had longer overall
      survival (OS) (10 vs. 3 months, P = 0.02). Smokers had a higher total mutational
      burden (TMB) (P = 0.01). Virus-positive patients had a lower TMB (P < 0.01) and
      improved OS (P = 0.02). Among virus-negative responders, NOTCH1 and SMARCA4 were
      more frequently mutated and frameshift events in tumor suppressor genes occurred
      more frequently (P = 0.03). Higher TMB and CD8+ T cell infiltrates predicted anti
      PD-1/L1 benefit (P < 0.01, P < 0.01, respectively) among virus-negative tumors.
      TIM-3/LAG-3 coexpression with PD-1 was higher on T cells among nonresponders (P =
      0.03 and 0.02, respectively). Somatic frameshift events in tumor suppressor genes
      and higher TMB among virus-negative SCCHN tumors predict anti-PD-1/L1 response.

PMID- 29467337
TI  - Nitric oxide-sensitive guanylyl cyclase stimulation improves experimental heart
      failure with preserved ejection fraction.
AB  - Heart failure with preserved ejection fraction (HFpEF) can arise from cardiac and
      vascular remodeling processes following long-lasting hypertension. Efficacy of
      common HF therapeutics is unsatisfactory in HFpEF. Evidence suggests that
      stimulators of the nitric oxide-sensitive soluble guanylyl cyclase (NOsGC) could
      be of use here. We aimed to characterize the complex cardiovascular effects of
      NOsGC stimulation using NO-independent stimulator BAY 41-8543 in a double
      transgenic rat (dTGR) model of HFpEF. We show a drastically improved survival
      rate of treated dTGR. We observed less cardiac fibrosis, macrophage infiltration,
      and gap junction remodeling in treated dTGR. Microarray analysis revealed that
      treatment of dTGR corrected the dysregulateion of cardiac genes associated with
      fibrosis, inflammation, apoptosis, oxidative stress, and ion channel function
      toward an expression profile similar to healthy controls. Treatment reduced
      systemic blood pressure levels and improved endothelium-dependent vasorelaxation
      of resistance vessels. Further comprehensive in vivo phenotyping showed an
      improved diastolic cardiac function, improved hemodynamics, and less
      susceptibility to ventricular arrhythmias. Short-term BAY 41-8543 application in
      isolated untreated transgenic hearts with structural remodeling significantly
      reduced the occurrence of ventricular arrhythmias, suggesting a direct nongenomic
      role of NOsGC stimulation on excitation. Thus, NOsGC stimulation was highly
      effective in improving several HFpEF facets in this animal model, underscoring
      its potential value for patients.

PMID- 29467339
TI  - Photoreactivities of the Antiseptics Dehydroacetic Acid and Sodium Dehydroacetate
      Used in Cosmetics.
AB  - Dehydroacetic acid (1) was found to induce photoisomerization, converting aldrin
      (3) and dieldrin (4) into photoaldrin (5) and photodieldrin (6), respectively,
      not only when irradiated with artificial light at wavelengths longer than 290 nm
      in air but also when exposed to sunlight in air. By contrast, sodium
      dehydroacetate (2) induced both photoisomerization, primarily converting 3 to 5
      and photoepoxidation, partially forming 6. Thus, because 2 is usually used as a
      water-soluble antiseptic, photo-erethism might occur due to the isomerization and
      epoxidation properties of this compound. The difference between the
      photoreactivity of 1 and that of 2 might be attributed to the spin density of the
      odd electron on the carbon atom in the respective radicals that were formed after
      photo-excited 1 and 2 caused H-abstraction.

PMID- 29467338
TI  - TCR-mimic bispecific antibodies targeting LMP2A show potent activity against EBV
      malignancies.
AB  - EBV infection is associated with a number of malignancies of clinical unmet need,
      including Hodgkin lymphoma, nasopharyngeal carcinoma, gastric cancer, and
      posttransplant lymphoproliferative disease (PTLD), all of which express the EBV
      protein latent membrane protein 2A (LMP2A), an antigen that is difficult to
      target by conventional antibody approaches. To overcome this, we utilized phage
      display technology and a structure-guided selection strategy to generate human T
      cell receptor-like (TCR-like) monoclonal antibodies with exquisite specificity
      for the LMP2A-derived nonamer peptide, C426LGGLLTMV434 (CLG), as presented on HLA
      A*02:01. Our lead construct, clone 38, closely mimics the native binding mode of
      a TCR, recognizing residues at position P3-P8 of the CLG peptide. To enhance
      antitumor potency, we constructed dimeric T cell engaging bispecific antibodies
      (DiBsAb) of clone 38 and an affinity-matured version clone 38-2. Both DiBsAb
      showed potent antitumor properties in vitro and in immunodeficient mice implanted
      with EBV transformed B lymphoblastoid cell lines and human T cell effectors.
      Clone 38 DiBsAb showed a stronger safety profile compared with its affinity
      matured variant, with no activity against EBV- tumor cell lines and a panel of
      normal tissues, and was less cross-reactive against HLA-A*02:01 cells pulsed with
      a panel of CLG-like peptides predicted from a proteomic analysis. Clone 38 was
      also shown to recognize the CLG peptide on other HLA-A*02 suballeles, including
      HLA-A*02:02, HLA-A*02:04, and HLA-A*02:06, allowing for its potential use in
      additional populations. Clone 38 DiBsAb is a lead candidate to treat EBV
      malignancies with one of the strongest safety profiles documented for TCR-like
      mAbs.

PMID- 29467340
TI  - Saltatory Conduction as an Electrostatic Compressional Wave in the Axoplasm.
AB  - Saltatory conduction is an essential phenomenon to facilitate the fast conduction
      in myelinated nerves. The conventional conductive models assumed electric
      circuits with local current along the axonal membrane to explain the nerve
      conduction in unmyelinated nerves. However, whether such models with local
      current can be also applied to the saltatory conduction in myelinated nerves is
      unknown. In this report, I propose a new model of saltatory conduction by
      focusing on the behavior of electric charges in the axoplasm, not limited to the
      membrane. In myelinated nerves, because of the large internodal length and the
      low ion channel density in the internodal segment, the whole cross-section of the
      internodal axoplasm would contribute to the signal conduction. Because the
      conducted signals originate from the sodium ion influx through the voltage-gated
      sodium (NaV) channel at the Ranvier's nodes, an individual conducted signal can
      be described as a single electrostatic compressional wave of positive charges in
      the internodal axoplasm. Based on this model, the total number of NaV channels in
      one Ranvier's node would regulate the strength of the wave. Also, the internodal
      length would be important for the faster conduction in larger myelinated axons.
      Based on the linear relationships between axonal diameter, internodal length, and
      conduction velocity, the internodal length would be inversely proportional to the
      ratio of the transmitted overall wave strength at a Ranvier's node to the
      original strength at the proximal adjacent node. This new mathematical model may
      have wide applicability and usability for the conduction in myelinated nerves.

PMID- 29467341
TI  - Retraction: Nucleophagy in Human Disease: Beyond the Physiological Role. [Tohoku
      J. Exp. Med., 2018, 244 (1), 75-81. doi: 10.1620/tjem.244.75. Review.].
AB  - Retracted Review article: Nucleophagy in Human Disease: Beyond the Physiological
      Role. [Tohoku J. Exp. Med., 2018, 244 (1), 75-81. doi: 10.1620/tjem.244.75.]The
      above Review article was published online on January 27, 2018. Soon after its
      publication (on February 1, 2018), Dr. Nian Fu and Prof. Linxi Chen informed the
      Editor-in-Chief, The Tohoku Journal of Experimental Medicine (TJEM), about
      serious violation of publication ethics. Indeed, Dr. Nian Fu and Prof. Linxi Chen
      were astonished to find their names as coauthors of this Review article, because
      they were not involved in the submission process of this Review article and they
      do not know any of other coauthors. In addition, the Review article is similar to
      their unpublished manuscript.After a thorough investigation in accordance with
      the recommendations of the Committee on Publication Ethics (COPE), the Editor-in
      Chief of TJEM decided to retract this Review article. The reasons for Retraction
      are summarized below: forged authors and an unexpected case of plagiarism.Forged
      authors: Dr. Nian Fu and Prof. Linxi Chen were added as co-authors of the Review
      article without their knowledge. In fact, the signature provided by Prof. Linxi
      Chen is apparently different from the signature of a coauthor, named Linxi Chen,
      on the AUTHORS' RESPONSIBILITY FORM, provided by the corresponding author of the
      Review article. More critically, the signature provided by Dr. Nian Fu is
      completely different from the signature of Nian Fu, because the Chinese
      characters are different between the two signatures. In addition, the replies
      from three authors (Ming Zhou, Hongwen Ji and Yong Xia) clearly indicate that
      they misunderstand the identity of Dr. Nina Fu. We also attempted to contact two
      authors, named Nian Fu and Linxi Chen, via e-mail. As expected, the forged
      authors did not respond to our inquiries, despite that their e-mail addresses
      appear to be active.An unexpected case of plagiarism: This Review article is
      similar to the unpublished manuscript prepared by Dr. Nian Fu and Prof. Linxi
      Chen. Moreover, two figures used in the Review article are identical to the
      preliminary figures of their unpublished manuscript. According to Dr. Nian Fu, a
      local agency for language editing had transferred their unpublished manuscript to
      a third party. Unfortunately, the check system of TJEM is not effective for
      plagiarism of unpublished materials. We believe that the corresponding author of
      the Review article included the names of the original two authors to avoid the
      criticism of plagiarism. Eventually, the corresponding author agreed to retract
      the Review article.We apologize for any inconvenience caused by this retraction
      to readers. We also hope that the publication of the plagiarized Review article
      will not trouble Dr. Nian Fu and Prof. Linxi Chen too much.

PMID- 29467342
TI  - Specific Health Guidance, the Nationwide Lifestyle Intervention Program Targeting
      Metabolic Syndrome, Seems to be Successful in Japan.

PMID- 29467343
TI  - How Should We Effectively Support Smoking Cessation at Health Checkup Opportunity
      and Induce More Quitters.

PMID- 29467344
TI  - Berberine inhibits glucose oxidation and insulin secretion in rat islets.
AB  - Glucose promotes insulin secretion primarily via its metabolism and the
      production of metabolic coupling factors in beta-cells. The activation of AMP
      activated protein kinase (AMPK), an energy sensor, results in a decrease in
      insulin secretion from beta-cells, but its mechanism remains largely unknown.
      Berberine, an oral anti-diabetic drug, has been shown to activate AMPK in
      multiple peripheral tissues. Here, we examined the effects of berberine and AMPK
      activation on insulin secretion and glucose oxidation in rat islets. Our results
      showed that berberine inhibited glucose-stimulated insulin secretion from rat
      islets with AMPK activation. When glucose concentration was elevated to 25
      mmol/L, the inhibitory action of berberine on insulin secretion disappeared.
      Furthermore, berberine significantly decreased oxygen consumption rate (OCR) and
      ATP production induced by high glucose in rat islets. Although adenovirus
      mediated overexpression of constituent-activated AMPK markedly decreased GSIS and
      OCR in rat islets, the inhibition of AMPK by compound C did not reverse berberine
      suppressed OCR. In addition, berberine attenuated glucose-stimulated expression
      of fatty acid synthase. These results indicate that berberine-mediated
      deceleration of glucose oxidation is tightly link to the decreased insulin
      secretion in islets independent of AMPK activation and inhibition of fatty acid
      synthesis may also contribute to the effect of berberine on insulin secretion.

PMID- 29467345
TI  - Ligustrazine Enhances the Hypnotic and Analgesic Effect of Ketamine in Mice.
AB  - The purpose of this study was to determine the effects of different
      concentrations of ligustrazine, an extract from Chinese herb, on ketamine
      requirement for hypnosis and analgesia in mice. In the hypnotic response study,
      mice were randomly allocated to receive saline or ligustrazine at 10, 20, 40, 80
      or 160 mg.kg-1 by intraperitoneal injection. Ketamine was administrated 15 min
      after ligustrazine injection. The hypnotic response was determined by assessing
      loss of the righting reflex (LORR) after ketamine injection. The dose of ketamine
      was determined by modified Dixon's up-and-down method in each group. In the
      analgesia study, different doses of ligustrazine were administrated 15 min before
      50 mg.kg-1 ketamine injection. The analgesia effects (pain threshold) were
      determined by heat radiation-induced tail-flick latency and evaluated before
      ligustrazine administration or 5, 15, 30 and 60 min after ketamine
      administration. The ED50 [95% confidence interval (CI)] for hypnosis induced by
      ketamine was 54.1 (44.8, 65.3) mg.kg-1. Ligustrazine dose-dependently decreased
      the ED50 for ketamine to induce hypnosis, which was [31.6 (26.2, 38.1)] mg.kg-1
      with the addition of 80 mg.kg-1 ligustrazine and [27.7 (22.6, 33.7)] mg.kg-1 with
      the addition of 160 mg.kg-1 ligustrazine, respectively (p<0.05). Ligustrazine at
      160 mg.kg-1 also increased pain threshold in the presence of ketamine.
      Ligustrazine enhanced the hypnotic effect of ketamine in a dose-dependent manner.
      Ligustrazine at a large dose also increased the analgesic effect of ketamine.

PMID- 29467346
TI  - Absorption and metabolism of orally administered collagen hydrolysates evaluated
      by the vascularly perfused rat intestine and liver in situ.
AB  - A number of studies have shown that oral administration of collagen hydrolysate
      (CH) results in the absorption of di- and tri-peptides. In order to understand
      the dynamics of CH absorption and metabolism, molecular profiles of
      hydroxyproline (Hyp) and Hyp-containing peptides (HCPs) were analyzed by in situ
      perfusion of rat intestine and liver. The total amount of absorbed HCPs during 1
      h of perfusion was 16.6 MUmol, which was significantly higher than that of free
      Hyp (6.6 MUmol). In addition, HCPs were also reliably detected in hepatic
      perfusate at the level higher than free Hyp. Thus, the results demonstrated that
      CH is absorbed predominantly as peptides, which subsequently enter systemic
      circulation. Size exclusion chromatography showed that perfusates include
      significant amount of HCPs larger than tripeptides, leading us to analyze these
      peptides in detail. Mass spectrometric analysis of intestinal perfusate finally
      identified three CH-derived peptides, which are surprisingly large as food
      derived circulating peptides. Peptide quantitation by liquid chromatography
      tandem mass spectrometry (LC-MS/MS) revealed that di- and tri-peptides, which are
      previously identified as major peptides in circulating blood, comprise only a
      part of HCPs in intestinal and liver perfusate. Finally, analysis of portal vein
      blood revealed that the larger peptides, such as pentadecapeptide identified in
      this study, could be absorbed in vivo. Taken all together, this study showed that
      peptides which are larger than tripeptide could reach to the circulation system
      after administration of CH, revealing previously unknown dynamics of absorption
      of CH.

PMID- 29467347
TI  - A cell-based interferon-tau assay with an interferon-stimulated gene 15 promoter.
AB  - Interferon-tau (IFNT) is known as an early pregnancy recognition signal in
      ruminants. An accurate and convenient IFNT detection system is desirable for the
      diagnosis of endometrial and trophoblastic functions, including gestation status,
      in cows. The aim of this study was to develop a new cell-based assay, which
      involved the stable introduction of an interferon-stimulated gene promoter to a
      luciferase reporter system. The reactivity of four interferon-stimulated genes to
      IFNT in Madin-Darby bovine kidney (MDBK) cells was confirmed using reverse
      transcription-quantitative PCR. The upstream region of the interferon-stimulated
      gene 15 ubiquitin-like modifier (ISG15) gene as the promoter of the reporter
      gene, which is more responsive to IFNT and other IFNs, was determined using the
      luciferase assay. The reporter gene with the ISG15 upstream region was stably
      transfected into MDBK cells using the PiggyBac vector system; this cell line
      responded to type I IFNs in a dose-dependent manner. Because of its convenience,
      this cell line is suitable for the quantification of IFNT as well as other type I
      IFNs activities.

PMID- 29467348
TI  - Combination of a cryosectioning method and section scanning electron microscopy
      for immuno-scanning electron microscopy.
AB  - We describe a novel immuno-scanning electron microscopy (SEM) technique that
      combines both Tokuyasu's cryosectioning and section SEM methods. In this
      technique, semithin cryosections, cut according to the Tokuyasu method, were
      adhered to glass microscope slides, immunostained for bio-molecules of interest
      and observed by confocal laser scanning microscopy. The same sections were
      subsequently embedded in epoxy resin and ultrathin sections were cut on an
      ultramicrotome. These were then observed by SEM using a backscattered electron
      detector. Correlation between immunofluorescence and SEM images was performed in
      the same area of the cryosection. Immuno-SEM was also performed using a
      FluoroNanogold-labeled secondary antibody. This novel immuno-SEM method can
      provide ultrastructural information of cell organelles in relation to associated
      molecules, such as Golgi- and ER-associated proteins. This novel immuno-SEM
      technique has the potential to be widely used.

PMID- 29467349
TI  - Targeting of severe fever with thrombocytopenia syndrome virus structural
      proteins to the ERGIC (endoplasmic reticulum Golgi intermediate compartment) and
      Golgi complex.
AB  - Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) is a newly
      emerged phlebovirus identified in China, Japan, and South Korea. Phlebovirus
      glycoproteins (GP) play a key role in targeting viral structural components to
      the budding compartments in the ER-Golgi intermediate compartment (ERGIC) and
      Golgi complex. However, the role of SFTSV GP in targeting structural proteins to
      the ERGIC and Golgi complex remains unresolved. In this study, we show that SFTSV
      GP plays a significant role in targeting RNA-dependent RNA polymerase (L) and
      nucleocapsid protein (NP) to the budding sites. Confocal microscopy was used to
      investigate the subcellular localization of SFTSV structural proteins. In SFTSV
      infected cells, GP and L localized to the ER, ERGIC and Golgi complex, whereas NP
      localized to the ERGIC and Golgi complex. In addition, GP colocalized with L and
      NP in infected cells. In cells singly transfected with GP, L or NP, GP localized
      to the same subcellular compartments as in infected cells. However, L or NP alone
      did not localize to the ER, ERGIC, or Golgi complex. Cotransfection experiments
      showed that GP altered the localization of L to the ERGIC and Golgi complex but
      not that of NP. Interestingly, plasmid-expressed NP fused with a hemagglutinin
      tag localized to the ERGIC and Golgi complex when expressed in SFTSV-infected
      cells and colocalised with GP, suggesting that GP plays a role in the subcellular
      localization of L and NP in infected cells. Thus, the SFTSV structural components
      start to assemble at the ERGIC to Golgi complex. GP is required for transporting
      L and NP to the ERGIC and Golgi complex. In addition, targeting of NP requires
      interaction with other factors besides GP.

PMID- 29467350
TI  - Influence of nitrous oxide on granule cell migration in the dentate gyrus of the
      neonatal rat.
AB  - For several decades, the neurotoxicities of anesthetics to the developing brain
      have been reported by many researchers focusing on various phenomena such as
      apoptosis, neurodegeneration, electrophysiological aberrations, and behavioral
      abnormalities. According to these reports, signals via N-methyl-D-aspartate
      receptors (NMDA-r) and/or gamma-aminobutyric acid type A receptors (GABAA-r) are
      implicated in the anesthetic neurotoxicity. On the other hand, during brain
      development, NMDA-r and GABAA-r are also recognized to play primary roles in
      neural cell migration. Therefore, anesthetics exposed in this period may
      influence the neural cell migration of neonates, and increase the number of hilar
      ectopic granule cells, which are reported to be a cause of continuous
      neurological deficits. To examine this hypothesis, we investigated
      immunohistochemically granule cell distribution in the hippocampal dentate gyrus
      of Wistar/ST rats after nitrous oxide (N2O) exposure. At postnatal day (P) 6, 5
      bromo-2'-deoxyuridine (BrdU) was administered to label newly generated cells.
      Then, rats were divided into groups (n = 6 each group), exposed to 50% N2O at P7,
      and evaluated at P21. As a result, we found that ectopic ratios (ratio of
      hilar/total granule cells generated at P6) were decreased in rats at P21 compared
      with those at P7, and increased in N2O exposed rats for over 120 min compared
      with the other groups. These results suggest that 50% N2O exposure for over 120
      min increases the ratios of ectopic granule cells in the rat dentate gyrus.

PMID- 29467351
TI  - Short and long photoperiods differentially exacerbate corticosterone-induced
      physical and psychological symptoms in mice.
AB  - Circadian disruption affects the pathogenesis and development of various
      diseases. Depression is one of the most common diseases that relate to circadian
      rhythm. In this study, we analyzed the effects of daily light/dark (LD)
      conditions on depression and other symptoms, and also analyzed the mixed effects
      of LD conditions and corticosterone treatment. Male adult C57BL/6 mice were
      treated with corticosterone in a normal LD cycle of 12 hours light and 12 hours
      dark (LD12 : 12), short day conditions of 6 hours light and 18 hours dark (LD6 :
      18), or long day conditions of 21 hours light and 3 hours dark (LD21 : 3). The
      activity rhythms of mice in aberrant LD conditions were entrained within 2 weeks.
      After 6 weeks of exposure, several behavioral tests were conducted.
      Corticosterone induced body weight gain and depression-like symptoms. The short
      or long LD conditions had little effect on vehicle-treated mice behavior.
      However, the aberrant LD conditions exacerbated the corticosterone-induced
      symptoms. Mice treated with corticosterone in LD6 : 18 showed exacerbated
      depression-like symptoms in a novelty suppressed feeding test. On the other hand,
      LD21 : 3 did not show any effects on mood, but enhanced corticosterone-induced
      body weight gain. These results indicated that aberrant LD conditions could act
      as an exacerbating factor for corticosterone-induced symptoms, and that short and
      long photoperiods induce different psychological and physiological changes. This
      corticosterone + aberrant LD model could be a useful animal model for
      investigating the effect of LD conditions on depression, obesity, and other
      symptoms in stressful circumstances.

PMID- 29467353
TI  - Can Tolvaptan Protect Renal Function in the Early Postoperative Period of Cardiac
      Surgery? - Results of a Single-Center Randomized Controlled Study.
AB  - BACKGROUND: Oral administration of tolvaptan, a vasopressin V2receptor
      antagonist, significantly reduces deterioration of renal function, which has
      recently been highlighted as an exacerbating factor for adverse events in
      patients with acute heart failure. In the present study we tested the hypothesis
      that concomitant administration of tolvaptan with a conventional diuretic is
      beneficial for perioperative body fluid management in patients who have undergone
      cardiac surgery.Methods and Results:In all, 280 patients who underwent cardiac
      surgery were prospectively randomized to concomitant treatment with tolvaptan and
      a conventional diuretic (tolvaptan group; 147 patients) or treatment with a
      conventional diuretic alone (control group; 133 patients). Groups were compared
      in terms of the time required to restore preoperative body weight and the
      incidence of worsening renal function (WRF), defined as an increase in the serum
      creatinine level >=0.3 mg/dL. The time required to restore preoperative body
      weight was significantly shorter in the tolvaptan than control group (mean [+/
      SD] 3.97+/-1.95 vs. 5.02+/-2.83 days, respectively; P<0.001). The incidence of
      WRF was significantly lower in the tolvaptan than control group (n=11 [7.5%] vs.
      n=25 [18.8%], respectively; P=0.011). CONCLUSIONS: Administration of tolvaptan
      with conventional diuretics in the early postoperative period after cardiac
      surgery could be beneficial in maintaining urine output without affecting renal
      function and may thus help avoid WRF.

PMID- 29467354
TI  - High Signal Intensity on T2-Weighted Cardiovascular Magnetic Resonance Imaging
      Predicts Life-Threatening Arrhythmic Events in Hypertrophic Cardiomyopathy
      Patients.
AB  - BACKGROUND: The prognostic value of high signal intensity on T2-weighted
      cardiovascular magnetic resonance imaging (T2 high signal) in hypertrophic
      cardiomyopathy (HCM) patients in a single-center cohort was investigated.Methods
      and Results:A total of 237 HCM patients (median age, 62 years; 143 male)
      underwent T2-weighted, cine and late gadolinium enhancement (LGE) imaging, and
      were followed (median duration, 3.4 years) for life-threatening arrhythmic
      events. The clinical and magnetic resonance imaging characteristics were
      extracted, and predictors of life-threatening arrhythmic events were assessed on
      multivariate analysis. LGE was present in 180 patients (75.9%). Median LGE score
      was 3 in a left ventricle 17-segment model. T2 high signal was present in 49
      patients (20.7%). The annual events rate was significantly higher in patients
      with extensive LGE (score >=4) than in those without (3.0%/year vs. 0.5%/year,
      P=0.011). On multivariate analysis, extensive LGE (hazard ratio, 5.650; 95% CI:
      1.263-25.000, P=0.024) as an independent predictor for life-threatening
      arrhythmic events. In patients with extensive LGE, the annual events rate was
      significantly higher in patients with T2 high signal than in those without
      (5.8%/year vs. 0.9%/year, P=0.008). CONCLUSIONS: Extensive LGE was an independent
      predictor of life-threatening arrhythmic events in HCM patients. Furthermore, T2
      high signal is useful for the risk stratification of serious arrhythmic events in
      patients with extensive LGE.

PMID- 29467352
TI  - Thioacetamide-induced hepatic fibrosis in the common marmoset.
AB  - The common marmoset (Callithrix jacchus) is a nonhuman primate that is used for
      preclinical research on stem cell transplantation therapies due to its similarity
      to human beings as well as its small size, enabling researchers to perform
      experiments without preparing a large number of cells. In this study, we
      developed a marmoset hepatic fibrosis model for regenerative medicine research.
      Six female marmosets aged 4-6 years were administered thioacetamide (TAA) at a
      dose of 2.5-40 mg/kg two or three times a week. Hepatic fibrosis was assessed by
      liver biopsy when blood chemistry indicated liver damage. Administration of TAA
      increased total bile acid, aspartate aminotransferase, and total bilirubin and
      decreased serum albumin levels. Following more than 11 weeks of continuous
      injection of TAA, histological analyses detected hepatic fibrosis in all animals.
      Type IV collagen 7S serum levels in animals with hepatic fibrosis were
      significantly higher than in normal animals as a possible marker of hepatic
      fibrosis in marmosets. Serial liver biopsies following the last administration of
      TAA revealed that induced fibrosis remained up to 11 weeks. The results suggest
      that continuous TAA administration induces persistent hepatic fibrosis in the
      common marmoset and this nonhuman primate hepatic fibrosis model have the
      possibility to evaluate the therapeutic effects of test samples to ameliorate
      hepatic fibrosis.

PMID- 29467355
TI  - Serial Change in Serum Chloride During Hospitalization Could Predict Heart
      Failure Death in Acute Decompensated Heart Failure Patients.
AB  - BACKGROUND: Although hyponatremia predicts morbidity and mortality in acute
      decompensated heart failure (ADHF), hypochloremia is also independently
      associated with poor prognosis in ADHF. Little is known, however, about the
      prognostic value of serial change in serum chloride during hospitalization in
      ADHF patients.Methods and Results:We prospectively studied 208 ADHF survivors
      after discharge and divided them into 4 groups according to serum chloride on
      admission and at discharge: (1) persistent hypochloremia group (n=12),
      hypochloremia both on admission and at discharge; (2) progressive hypochloremia
      group (n=42), development of hypochloremia after admission; (3) improved
      hypochloremia group (n=14), hypochloremia only on admission; and (4) no
      hypochloremia group, no hypochloremia during hospitalization (n=140). During a
      mean follow-up period of 1.86+/-0.76 years, 20 of 208 patients had heart failure
      death (HFD). In a model adjusted for hyponatremia, hypochloremia both on
      admission and at discharge was still significantly associated with HFD.
      Hyponatremia, however, was not significantly associated with HFD after adjustment
      for hypochloremia. Patients with persistent hypochloremia (HR, 9.13; 95% CI: 2.56
      32.55) and with progressive hypochloremia (HR, 4.65; 95% CI: 1.61-13.4) had a
      significantly greater risk of HFD than those without hypochloremia during
      hospitalization. CONCLUSIONS: Both persistent hypochloremia and progressive
      hypochloremia during hospitalization are associated with HFD in ADHF patients.

PMID- 29467356
TI  - Endogenous Interleukin-1beta Is Implicated in Intraplaque Hemorrhage in
      Apolipoprotein E Gene Null Mice.
AB  - BACKGROUND: Intraplaque hemorrhage (IPH) has been implicated in plaque
      instability and rupture in atherosclerotic lesions, although the mechanisms by
      which IPH progresses remain largely unknown. In this study, apolipoprotein E
      deficient mice with carotid artery ligation and cuff placement around the artery
      were used, and pro-inflammatory cytokines that are implicated in IPH were
      analyzed.Methods and Results:The expression of interleukin-1beta (IL-1beta)
      increased significantly following cuff placement compared with mice with carotid
      artery ligation alone. IPH occurred in the cuff-placed carotid artery following
      treatment with the negative control (NC) small interfering RNA (siRNA). However,
      the occurrence was significantly reduced in the cuff-placed carotid artery
      following treatment with an IL-1beta siRNA. Neovessel formation was significantly
      reduced in the carotid artery treated with the NC siRNA compared with that
      treated with IL-1beta siRNA. IL-1beta significantly inhibited the tube formation
      and wound healing capacities of vascular endothelial cells in vitro. Furthermore,
      immunostaining of matrix metalloproteinase-9 (MMP-9) significantly increased in
      the carotid artery treated with the NC siRNA compared with that treated with IL
      1beta siRNA. CONCLUSIONS: These results suggest that endogenous IL-1beta is
      implicated in the progression of IPH via the inhibition of physiological
      angiogenesis in the atherosclerotic plaque, leading to the formation of leaky
      neovessels. Furthermore, the stimulation of MMP-9 expression may also contribute
      to the formation of leaky neovessels.

PMID- 29467357
TI  - Improvement of Libman-Sacks Endocarditis With Combined Hydroxychloroquine-Vitamin
      K Antagonist Therapy in a Primary Antiphospholipid Syndrome Patient.

PMID- 29467358
TI  - [Chinese Journal of Nuclear Medicine and Molecular Imaging Volume 38, Number 1,
      January 25, 2018].

PMID- 29467359
TI  - Evaluation of a Portable Doppler Ultrasound Gating Device for Fetal Cardiac MR
      Imaging: Initial Results at 1.5T and 3T.
AB  - PURPOSE: Fetal cardiac MRI has the potential to play an important role in the
      assessment of fetal cardiac pathologies, but it is up to now not feasible due to
      a missing gating method. The purpose of this work was the evaluation of Doppler
      ultrasound (DUS) for external fetal cardiac gating with regard to compatibility,
      functionality, and reliability. Preliminary results were assessed performing
      fetal cardiac MRI. METHODS: An MRI conditional DUS device was developed to obtain
      a gating signal from the fetal heart. The MRI compatibility was evaluated at 1.5T
      and 3T using B1 field maps and gradient echo images. The quality and sensitivity
      of the DUS device to detect the fetal heart motion for cardiac gating were
      evaluated outside the MRI room in 15 fetuses. A dynamic fetal cardiac phantom was
      employed to evaluate distortions of the DUS device and gating signal due to
      electromagnetic interferences at 1.5T and 3T. In the first in vivo experience,
      dynamic fetal cardiac images were acquired in four-chamber view at 1.5T and 3T in
      two fetuses. RESULTS: The maximum change in the B1 field and signal intensity
      with and without the DUS device was <6.5% for 1.5T and 3T. The sensitivity of the
      DUS device to detect the fetal heartbeat was 99.1%. Validation of the DUS device
      using the fetal cardiac phantom revealed no electromagnetic interferences at 1.5T
      or 3T and a high correlation to the simulated heart frequencies. Fetal cardiac
      cine images were successfully applied and showed good image quality. CONCLUSION:
      An MR conditional DUS gating device was developed and evaluated revealing safety,
      compatibility, and reliability for different field strengths. In a preliminary
      experience, the DUS device was successfully applied for in vivo fetal cardiac
      imaging at 1.5T and 3T.

PMID- 29467360
TI  - Atypical Presentation of Acute Coronary Syndrome and Importance of Wellens'
      Syndrome.
AB  - BACKGROUND Acute coronary syndrome (ACS) is a common and potentially life
      threatening condition encountered in emergency departments. Despite its dreaded
      nature, nearly one-third of ACS present without chest pain and may mislead
      clinicians. Additionally, Wellens' syndrome is a pre-infarction stage of
      significant proximal left anterior descending (LAD) artery stenosis, which can
      lead to extensive anterior wall myocardial infarction without timely
      intervention.  CASE REPORT We report the case of a 74-year-old woman presenting
      with isolated throat pain and Wellens' pattern in the initial EKG, which prompted
      the proper workup and management. Subsequently, coronary angiogram revealed more
      than 90% occlusion of the proximal LAD artery, and a drug-eluting stent was
      deployed. The patient did well after the procedure and the follow-up at 2 weeks
      after discharge was uneventful.   CONCLUSIONS This case highlights the importance
      of awareness of atypical presentation of ACS and importance of Wellens' syndrome.
      We also discuss the incidence of craniofacial symptoms of ACS, and the
      epidemiology, pathophysiology, management, and prognosis of Wellens' syndrome.

PMID- 29467361
TI  - Resveratrol Attenuates Cognitive Deficits of Traumatic Brain Injury by Activating
      p38 Signaling in the Brain.
AB  - BACKGROUND Traumatic brain injury (TBI) is characterized by cognitive deficits,
      which was associated with brain oxidative stress and apoptosis. Resveratrol (RSV)
      is an anti-apoptotic and anti-oxidative. This study aimed to investigate
      neuroprotective effects and involved molecular mechanisms in TBI. MATERIAL AND
      METHODS RSV and p38 inhibitor were administrated to TBI rats. Cognitive deficits
      were evaluated by Morris water maze assay. Reactive oxygen species (ROS) and
      apoptosis were detected in rat brains by fluorescent staining. Western blotting
      was used to assess the phosphorylation of p38 and the expression levels of Nrf2,
      HO1, and activated caspase-3. RESULTS RSV administration attenuated cognitive
      deficits of TBI rats. The ROS generation and apoptosis in the brain of TBI rats
      were suppressed by RSV treatment. Moreover, RSV treatment recovered activation of
      p38/Nrf2/HO1 signaling pathway. The co-administration of p38 inhibitor impaired
      RSV's attenuating effects on cognitive deficits, brain apoptosis, and ROS
      generation. CONCLUSIONS RSV attenuated cognitive deficits of TBI by inhibiting
      oxidative stress-mediated apoptosis via targeting p38/Nrf2 signaling.

PMID- 29467362
TI  - Media use and brain development during adolescence.
AB  - The current generation of adolescents grows up in a media-saturated world.
      However, it is unclear how media influences the maturational trajectories of
      brain regions involved in social interactions. Here we review the neural
      development in adolescence and show how neuroscience can provide a deeper
      understanding of developmental sensitivities related to adolescents' media use.
      We argue that adolescents are highly sensitive to acceptance and rejection
      through social media, and that their heightened emotional sensitivity and
      protracted development of reflective processing and cognitive control may make
      them specifically reactive to emotion-arousing media. This review illustrates how
      neuroscience may help understand the mutual influence of media and peers on
      adolescents' well-being and opinion formation.

PMID- 29467363
TI  - Enhancing Hi-C data resolution with deep convolutional neural network HiCPlus.
AB  - Although Hi-C technology is one of the most popular tools for studying 3D genome
      organization, due to sequencing cost, the resolution of most Hi-C datasets are
      coarse and cannot be used to link distal regulatory elements to their target
      genes. Here we develop HiCPlus, a computational approach based on deep
      convolutional neural network, to infer high-resolution Hi-C interaction matrices
      from low-resolution Hi-C data. We demonstrate that HiCPlus can impute interaction
      matrices highly similar to the original ones, while only using 1/16 of the
      original sequencing reads. We show that the models learned from one cell type can
      be applied to make predictions in other cell or tissue types. Our work not only
      provides a computational framework to enhance Hi-C data resolution but also
      reveals features underlying the formation of 3D chromatin interactions.

PMID- 29467364
TI  - Nanoscale kinetic segregation of TCR and CD45 in engaged microvilli facilitates
      early T cell activation.
AB  - T cells have a central function in mounting immune responses. However, mechanisms
      of their early activation by cognate antigens remain incompletely understood.
      Here we use live-cell multi-colour single-molecule localization microscopy to
      study the dynamic separation between TCRs and CD45 glycoprotein phosphatases in
      early cell contacts under TCR-activating and non-activating conditions. Using
      atomic force microscopy, we identify these cell contacts with engaged microvilli
      and characterize their morphology, rigidity and dynamics. Physical modelling and
      simulations of the imaged cell interfaces quantitatively capture the TCR-CD45
      separation. Surprisingly, TCR phosphorylation negatively correlates with TCR-CD45
      separation. These data support a refined kinetic-segregation model. First,
      kinetic-segregation occurs within seconds from TCR activation in engaged
      microvilli. Second, TCRs should be segregated, yet not removed too far, from CD45
      for their optimal and localized activation within clusters. Our combined imaging
      and computational approach prove an important tool in the study of dynamic
      protein organization in cell interfaces.

PMID- 29467365
TI  - High-performance graphdiyne-based electrochemical actuators.
AB  - Electrochemical actuators directly converting electrical energy to mechanical
      energy are critically important for artificial intelligence. However, their
      energy transduction efficiency is always lower than 1.0% because electrode
      materials lack active units in microstructure, and their assembly systems can
      hardly express the intrinsic properties. Here, we report a molecular-scale active
      graphdiyne-based electrochemical actuator with a high electro-mechanical
      transduction efficiency of up to 6.03%, exceeding that of the best-known
      piezoelectric ceramic, shape memory alloy and electroactive polymer reported
      before, and its energy density (11.5 kJ m-3) is comparable to that of mammalian
      skeletal muscle (~8 kJ m-3). Meanwhile, the actuator remains responsive at
      frequencies from 0.1 to 30 Hz with excellent cycling stability over 100,000
      cycles. Furthermore, we verify the alkene-alkyne complex transition effect
      responsible for the high performance through in situ sum frequency generation
      spectroscopy. This discovery sheds light on our understanding of actuation
      mechanisms and will accelerate development of smart actuators.

PMID- 29467366
TI  - Human Semaphorin-4A drives Th2 responses by binding to receptor ILT-4.
AB  - Semaphorin-4A (Sema4A) has been implicated in the co-stimulation of T cells and
      drives Th1 immune responses by binding to the receptor T-cell immunoglobulin and
      mucin domain protein 2 (Tim-2) in mice. Here we show that human, but not murine,
      Sema4A is preferentially expressed on antigen-presenting cells, and co-stimulates
      CD4+ T-cell proliferation and drives Th2 responses. By employing two independent
      cloning strategies, we demonstrate that Immunoglobulin-like transcript 4 (ILT-4)
      is a receptor for human SEMA4A (hSEMA4A) on activated CD4+ T cells. We also find
      hSEMA4A to be highly expressed in human asthmatic lung tissue, implying its
      potential function in disease pathogenesis. Our study defines a different
      biological function of hSEMA4A from its murine homolog through its binding to the
      receptor of ILT-4 to co-stimulate CD4+T cells and regulate Th2 cells
      differentiation.

PMID- 29467367
TI  - Removal of artificial sweeteners and their effects on microbial communities in
      sequencing batch reactors.
AB  - Concern is growing over contamination of the environment with artificial
      sweeteners (ASWs) because of their widespread existence in wastewater treatment
      plants (WWTPs). To evaluate ASWs removal and the effect on activated sludge,
      acesulfame (ACE), sucralose (SUC), cyclamate (CYC) and saccharin (SAC) were
      introduced individually or in mixture to sequencing batch reactors (SBRs) in
      environmentally relevant concentrations (100 ppb) for 100 days. Comparisons
      between ACE removal in a full-scale WWTP and in lab-scale SBRs were conducted.
      Results showed that CYC and SAC were completely removed, whereas SUC was
      persistent. However, ACE removal in lab-scale SBRs was significantly greater than
      in the full-scale WWTP. In SBRs, chemical oxygen demand (COD), ammonia nitrogen
      (NH4+-N) and total nitrogen (TN) removal appeared unchanged after adding ASWs (p
      > 0.05). Adenosine triphosphate (ATP) concentrations and triphenyl tetrazolium
      chloride-dehydrogenase activity (TTC-DHA) declined significantly (p < 0.05). The
      mixed ASWs had more evident effects than the individual ASWs. Microbial community
      analyses revealed that Proteobacteria decreased obviously, while Bacteroidetes,
      Chloroflexi and Actinobacteria were enriched with the addition of ASWs.
      Redundancy Analysis (RDA) indicated ACE had a greater impact on activated sludge
      than the other ASWs.

PMID- 29467368
TI  - Culture-free bacterial detection and identification from blood with rapid,
      phenotypic, antibiotic susceptibility testing.
AB  - The current culture-based approach for the diagnosis of bloodstreams infection is
      incommensurate with timely treatment and curbing the prevalence of multi-drug
      resistant organisms (MDROs) due to its long time-to-result. Bloodstream
      infections typically involve extremely low (e.g., <10 colony-forming unit
      (CFU)/mL) bacterial concentrations that require a labor-intensive process and as
      much as 72 hours to yield a diagnosis. Here, we demonstrate a culture-free
      approach to achieve rapid diagnosis of bloodstream infections. An immuno
      detection platform with intrinsic signal current amplification was developed for
      the ultrasensitive, rapid detection, identification (ID) and antibiotic
      susceptibility testing (AST) of infections. With its capability of monitoring
      short-term (1-2 hours) bacterial growth in blood, the platform is able to provide
      84-minute simultaneous detection and ID in blood samples below the 10 CFU/mL
      level and 204-minute AST. The susceptible-intermediate-resistant AST capacity was
      demonstrated.

PMID- 29467370
TI  - The impact of computed high b-value images on the diagnostic accuracy of DWI for
      prostate cancer: A receiver operating characteristics analysis.
AB  - To evaluate the performance of computed high b value diffusion-weighted images
      (DWI) in prostate cancer detection. 97 consecutive patients who had undergone
      multiparametric MRI of the prostate followed by biopsy were reviewed. Five
      radiologists independently scored 138 lesions on native high b-value images (b =
      1200 s/mm2), apparent diffusion coefficient (ADC) maps, and computed high b-value
      images (contrast equivalent to b = 2000 s/mm2) to compare their diagnostic
      accuracy. Receiver operating characteristic (ROC) analysis and McNemar's test
      were performed to assess the relative performance of computed high b value DWI,
      native high b-value DWI and ADC maps. No significant difference existed in the
      area under the curve (AUC) for ROCs comparing B1200 (b = 1200 s/mm2) to computed
      B2000 (c-B2000) in 5 readers. In 4 of 5 readers c-B2000 had significantly
      increased sensitivity and/or decreased specificity compared to B1200 (McNemar's p
      < 0.05), at selected thresholds of interpretation. ADC maps were less accurate
      than B1200 or c-B2000 for 2 of 5 readers (P < 0.05). This study detected no
      consistent improvement in overall diagnostic accuracy using c-B2000, compared
      with B1200 images. Readers detected more cancer with c-B2000 images (increased
      sensitivity) but also more false positive findings (decreased specificity).

PMID- 29467369
TI  - Transcriptomic signature of drought response in pearl millet (Pennisetum glaucum
      (L.) and development of web-genomic resources.
AB  - Pearl millet, (Pennisetum glaucum L.), an efficient (C4) crop of arid/semi-arid
      regions is known for hardiness. Crop is valuable for bio-fortification combating
      malnutrition and diabetes, higher caloric value and wider climatic resilience.
      Limited studies are done in pot-based experiments for drought response at gene
      expression level, but field-based experiment mimicking drought by withdrawal of
      irrigation is still warranted. We report de novo assembly-based transcriptomic
      signature of drought response induced by irrigation withdrawal in pearl millet.
      We found 19983 differentially expressed genes, 7595 transcription factors, gene
      regulatory network having 45 hub genes controlling drought response. We report
      34652 putative markers (4192 simple sequence repeats, 12111 SNPs and 6249
      InDels). Study reveals role of purine and tryptophan metabolism in ABA
      accumulation mediating abiotic response in which MAPK acts as major intracellular
      signal sensing drought. Results were validated by qPCR of 13 randomly selected
      genes. We report the first web-based genomic resource (
      http://webtom.cabgrid.res.in/pmdtdb/ ) which can be used for candidate genes
      based SNP discovery programs and trait-based association studies. Looking at
      climatic change, nutritional and pharmaceutical importance of this crop, present
      investigation has immense value in understanding drought response in field
      condition. This is important in germplasm management and improvement in endeavour
      of pearl millet productivity.

PMID- 29467371
TI  - Predatory flying squids are detritivores during their early planktonic life.
AB  - Cephalopods are primarily active predators throughout life. Flying squids (family
      Ommastrephidae) represents the most widely distributed and ecologically important
      family of cephalopods. While the diets of adult flying squids have been
      extensively studied, the first feeding diet of early paralarvae remains a
      mystery. The morphology of this ontogenetic stage notably differs from other
      cephalopod paralarvae, suggesting a different feeding strategy. Here, a
      combination of Laser Capture Microdissection (LCM) and DNA metabarcoding of wild
      collected paralarvae gut contents for eukaryotic 18S v9 and prokaryotic 16S rRNA
      was applied, covering almost every life domain. The gut contents were mainly
      composed by fungus, plants, algae and animals of marine and terrestrial origin,
      as well as eukaryotic and prokaryotic microorganisms commonly found in fecal
      pellets and particulate organic matter. This assemblage of gut contents is
      consistent with a diet based on detritus. The ontogenetic shift of diet from
      detritivore suspension feeding to active predation represents a unique life
      strategy among cephalopods and allows ommastrephid squids to take advantage of an
      almost ubiquitous and accessible food resource during their early stages. LCM was
      successfully applied for the first time to tiny, wild-collected marine organisms,
      proving its utility in combination with DNA metabarcoding for dietary studies.

PMID- 29467372
TI  - Chiral Ag23 nanocluster with open shell electronic structure and helical face
      centered cubic framework.
AB  - We report the synthesis and crystal structure of a nanocluster composed of 23
      silver atoms capped by 8 phosphine and 18 phenylethanethiolate ligands. X-ray
      crystallographic analysis reveals that the kernel of the Ag nanocluster adopts a
      helical face-centered cubic structure with C2 symmetry. The thiolate ligands show
      two binding patterns with the surface Ag atoms: tri- and tetra-podal types. The
      tetra-coordination mode of thiolate has not been found in previous Ag
      nanoclusters. No counter ion (e.g., Na+ and NO3-) is found in the single-crystal
      and the absence of such ions is also confirmed by X-ray photoelectron
      spectroscopy analysis, indicating electrical neutrality of the nanocluster.
      Interestingly, the nanocluster has an open shell electronic structure (i.e.,
      23(Ag 5s1)-18(SR) = 5e), as confirmed by electron paramagnetic resonance
      spectroscopy. Time-dependent density functional theory calculations are performed
      to correlate the structure and optical absorption/emission spectra of the Ag
      nanocluster.

PMID- 29467373
TI  - Deep learning based tissue analysis predicts outcome in colorectal cancer.
AB  - Image-based machine learning and deep learning in particular has recently shown
      expert-level accuracy in medical image classification. In this study, we combine
      convolutional and recurrent architectures to train a deep network to predict
      colorectal cancer outcome based on images of tumour tissue samples. The novelty
      of our approach is that we directly predict patient outcome, without any
      intermediate tissue classification. We evaluate a set of digitized haematoxylin
      eosin-stained tumour tissue microarray (TMA) samples from 420 colorectal cancer
      patients with clinicopathological and outcome data available. The results show
      that deep learning-based outcome prediction with only small tissue areas as input
      outperforms (hazard ratio 2.3; CI 95% 1.79-3.03; AUC 0.69) visual histological
      assessment performed by human experts on both TMA spot (HR 1.67; CI 95% 1.28
      2.19; AUC 0.58) and whole-slide level (HR 1.65; CI 95% 1.30-2.15; AUC 0.57) in
      the stratification into low- and high-risk patients. Our results suggest that
      state-of-the-art deep learning techniques can extract more prognostic information
      from the tissue morphology of colorectal cancer than an experienced human
      observer.

PMID- 29467374
TI  - Multi-terminal spin valve in a strong Rashba channel exhibiting three resistance
      states.
AB  - In a strong spin-orbit interaction system, the existence of three resistance
      states were observed when two ferromagnetic (FM) contacts were used as current
      terminals while a separate normal metal contact pair was used as voltage
      terminals. This result is strikingly different from ordinary spin valve or
      magnetic tunnel junction devices, which have only two resistance states
      corresponding to parallel (RP) and antiparallel (RAP) alignments of the FM
      contacts. Our experimental results on a quantum well layer with a strong Rashba
      effect clearly exhibit unequal antiparallel states, i.e., RAP(1) > RP > RAP(2),
      up to room temperature. The three-states are observed without any degradation
      when the distance between the non-magnetic voltage probe and the ferromagnetic
      current probe was increased up to 1.6 mm.

PMID- 29467375
TI  - Phosphorus addition changes belowground biomass and C:N:P stoichiometry of two
      desert steppe plants under simulated N deposition.
AB  - Many studies have reported that increasing atmospheric nitrogen (N) deposition
      broadens N:phosphorus (P) in both soils and plant leaves and potentially
      intensifies P limitation for plants. However, few studies have tested whether P
      addition alleviates N-induced P limitation for plant belowground growth. It is
      also less known how changed N:P in soils and leaves affect plant belowground
      stoichiometry, which is significant for maintaining key belowground ecological
      processes. We conducted a multi-level N:P supply experiment (varied P levels
      combined with constant N amount) for Glycyrrhiza uralensis (a N fixing species)
      and Pennisetum centrasiaticum (a grass) from a desert steppe in Northwest China
      during 2011-2013. Results showed that increasing P addition increased the
      belowground biomass and P concentrations of both species, resulting in the
      decreases in belowground carbon (C):P and N:P. These results indicate that P
      inputs alleviated N-induced P limitation and hence stimulated belowground growth.
      Belowground C:N:P stoichiometry of both species, especially P. centrasiaticum,
      tightly linked to soil and green leaf C:N:P stoichiometry. Thus, the decoupling
      of C:N:P ratios in both soils and leaves under a changing climate could directly
      alter plant belowground stoichiometry, which will in turn have important
      feedbacks to primary productivity and C sequestration.

PMID- 29467376
TI  - Changes in functional brain network topology after successful and unsuccessful
      corpus callosotomy for Lennox-Gastaut Syndrome.
AB  - Corpus callosotomy (CC) is an effective palliative surgical treatment for
      patients with Lennox-Gastaut Syndrome (LGS). However, research on the long-term
      functional effects of CC is sparse. We aimed to investigate these effects and
      their associated clinical conditions over the two years after CC. Long-term
      clinical EEG recordings of 30 patients with LGS who had good and bad seizure
      outcome after CC were collected and retrospectively studied. It was found that CC
      caused brain network 'hubs' to shift from paramedian to lateral regions in the
      good-recovery group, which reorganized the brain network into a more homogeneous
      state. We also found increased local clustering coefficients in patients with bad
      outcomes and decreases, implying enhanced network integration, in patients with
      good outcomes. The small worldness of brain networks in patients with good
      outcomes increased in the two years after CC, whereas it decreased in patients
      with bad outcomes. The covariation of small-worldness with the rate of reduction
      in seizure frequency suggests that this can be used as an indicator of CC
      outcome. Local and global network changes during the long-term state might be
      associated with the postoperative recovery process and could serve as indicators
      for CC outcome and long-term LGS recovery.

PMID- 29467377
TI  - Evolution of extrema features reveals optimal stimuli for biological state
      transitions.
AB  - The ability to define the unique features of an input stimulus needed to control
      switch-like behavior in biological systems is an important problem in
      computational biology and medicine. We show in this study how highly complex and
      intractable optimization problems can be simplified by restricting the search to
      the signal's extrema as key feature points, and evolving the extrema features
      towards optimal solutions that closely match solutions derived from gradient
      based methods. Our results suggest a model-independent approach for solving a
      class of optimization problems related to controlling switch-like state
      transitions.

PMID- 29467378
TI  - InForm software: a semi-automated research tool to identify presumptive human
      hepatic progenitor cells, and other histological features of pathological
      significance.
AB  - Hepatic progenitor cells (HPCs) play an important regenerative role in acute and
      chronic liver pathologies. Liver disease research often necessitates the grading
      of disease severity, and pathologists' reports are the current gold-standard for
      assessment. However, it is often impractical to recruit pathologists in large
      cohort studies. In this study we utilise PerkinElmer's "InForm" software package
      to semi-automate the scoring of patient liver biopsies, and compare outputs to a
      pathologist's assessment. We examined a cohort of eleven acute hepatitis samples
      and three non-alcoholic fatty liver disease (NAFLD) samples, stained with HPC
      markers (GCTM-5 and Pan Cytokeratin), an inflammatory marker (CD45), Sirius Red
      to detect collagen and haematoxylin/eosin for general histology. InForm was
      configured to identify presumptive HPCs, CD45+ve inflammatory cells, areas of
      necrosis, fat and collagen deposition (p < 0.0001). Hepatitis samples were then
      evaluated both by a pathologist using the Ishak-Knodell scoring system, and by
      InForm through customised algorithms. Necroinflammation as evaluated by a
      pathologist, correlated with InForm outputs (r2 = 0.8192, p < 0.05). This study
      demonstrates that the InForm software package provides a useful tool for liver
      disease research, allowing rapid, and objective quantification of the presumptive
      HPCs and identifies histological features that assist with assessing liver
      disease severity, and potentially can facilitate diagnosis.

PMID- 29467379
TI  - Fluvirucin B6, a new macrolactam isolated from a marine-derived actinomycete of
      the genus Nocardiopsis.
AB  - A new 14-membered macrolactam natural product, fluvirucin B6 (1), was isolated
      from a marine-derived actinomycete, Nocardiopsis sp. CNQ-115, via HPLC-UV guided
      isolation. The chemical structure of 1 was elucidated by 1D and 2D NMR
      spectroscopic data analysis. Compound 1 showed a weak activity against Gram
      positive bacteria, whereas it was inactive against Gram-negative bacteria.

PMID- 29467380
TI  - Planctopirus hydrillae sp. nov., an antibiotic producing Planctomycete isolated
      from the aquatic plant Hydrilla and its whole genome shotgun sequence analysis.
AB  - An antibiotic producing novel Planctomycete strain, designated JC280T, was
      isolated from the surface of the plant Hydrilla verticillata collected from an
      alkaline lake (Buffalo lake), University of Hyderabad, Hyderabad, India. The
      morphological and chemotaxonomic properties of strain JC280T were in agreement
      with the characteristics of the genus Planctopirus. The cell shape was spherical
      to ovoid and some were tear drop shaped. The cells were Gram-stain-negative
      divided by budding presenting stalks and rosette formation and were non
      sporulating. Crateriform structures with a sub-polar flagellum were observed.
      Characteristic polyamines were putrescine and spermidine. Diagnostic polar lipids
      were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, an
      unidentified phospholipid (PL1), unidentified glycolipids (GL1-2), an
      unidentified aminophospholipid (APL), and an unidentified lipid (L3). Major
      (>10%) fatty acids were C16:0, C17:1omega8c, C18:1omega9c, and summed feature-3.
      Major (88%) respiratory quinone was MK-6 with minor amount (12%) of MK-7. Strain
      JC280T showed 99.7% 16S rRNA gene sequence similarity with Planctopirus
      limnophila DSM 3776T. To resolve their full taxonomic position, the genome
      sequence was obtained and compared with the available P. limnophila DSM 3776T
      genome. The genome sequence of strain JC280T was 5,750,243 bp in size with a
      total of 4490 protein-coding genes, 66 RNA genes, and 2 CRISPR repeats. Based on
      whole-genome statistics, ANI value, in silico DDH, diversity of secondary
      metabolite biosynthetic gene clusters, distinct physiological, biochemical and
      chemotaxonomic differences, strain JC280T represents a new species in the genus
      Planctopirus, for which the name Planctopirus hydrillae sp. nov. is proposed. The
      type strain is JC280T (=KCTC 42880T = LMG 29153T).

PMID- 29467381
TI  - TMCO1 is essential for ovarian follicle development by regulating ER Ca2+ store
      of granulosa cells.
AB  - TMCO1 (transmembrane and coiled-coil domains 1) is an endoplasmic reticulum (ER)
      transmembrane protein that actively prevents Ca2+ stores from overfilling. To
      characterize its physiological function(s), we generated Tmco1-/- knockout (KO)
      mice. In addition to the main clinical features of human cerebrofaciothoracic
      (CFT) dysplasia spectrum, Tmco1-/- females manifest gradual loss of ovarian
      follicles, impaired ovarian follicle development, and subfertility with a
      phenotype analogous to the premature ovarian failure (POF) in women. In line with
      the role of TMCO1 as a Ca2+ load-activated Ca2+ channel, we have detected a
      supernormal Ca2+ signaling in Tmco1-/- granulosa cells (GCs). Interestingly,
      although spontaneous Ca2+ oscillation pattern was altered, ER Ca2+ stores of
      germinal vesicle (GV) stage oocytes and metaphase II (MII) arrested eggs were
      normal upon Tmco1 ablation. Combined with RNA-sequencing analysis, we also
      detected increased ER stress-mediated apoptosis and enhanced reactive oxygen
      species (ROS) level in Tmco1-/- GCs, indicating the dysfunctions of GCs upon
      TMCO1 deficiency. Taken together, these results reveal that TMCO1 is essential
      for ovarian follicle development and female fertility by maintaining ER Ca2+
      homeostasis of GCs, disruption of which causes ER stress-mediated apoptosis and
      increased cellular ROS level in GCs and thus leads to impaired ovarian follicle
      development.

PMID- 29467382
TI  - KRAB-type zinc-finger proteins PITA and PISA specifically regulate p53-dependent
      glycolysis and mitochondrial respiration.
AB  - Few p53 regulators participate in selective control of p53-mediated cellular
      metabolism. How p53-mediated aerobic and glycolytic pathways are negatively
      regulated remains largely unclear. Here, we identified two KRAB-type zinc-finger
      proteins, PITA (p53 inhibitor of TIGAR activation) and PISA (p53 inhibitor of
      SCO2 activation), as selective regulators of p53 in metabolic control. PITA and
      PISA interact with p53 and specifically suppress transcription of the glycolysis
      regulator TIGAR and the oxidation phosphorylation regulator SCO2, respectively.
      Importantly, PITA transgenic mice exhibited increased 6-phosphofructokinase 1
      (PFK1) activity and an elevated glycolytic rate, whereas PISA transgenic mice had
      decreased cytochrome c oxidase activity and reduced mitochondrial respiration. In
      response to glucose starvation, PITA dissociates from p53, resulting in
      activation of p53 and induction of TIGAR, which inhibited aerobic glycolysis.
      Prolonged starvation leads to PISA dissociation from p53 and induction of SCO2
      and p53-promoted mitochondrial respiration. The dynamic regulation of PITA and
      PISA upon metabolic stress is dependent on ATM kinase-mediated phosphorylation of
      PITA and PISA. Furthermore, in human colorectal cancers, the elevated expression
      of PITA and PISA correlates with cancer progression. Depletion of PITA or PISA in
      colorectal cancer cells reduced the cell proliferation, migration and invasion.
      These results identify PITA and PISA as selective regulators of p53-mediated
      glycolysis and mitochondrial respiration and provide novel insights into the role
      of p53 network in cell metabolic control.

PMID- 29467383
TI  - Circulating tumor DNA 5-hydroxymethylcytosine as a novel diagnostic biomarker for
      esophageal cancer.

PMID- 29467384
TI  - Structural insight into the Zika virus capsid encapsulating the viral genome.

PMID- 29467385
TI  - The novel dithiocarbamate, DpdtC suppresses HER2-overexpressed cancer cells by up
      regulating NDRG1 via inactivation of HER2-ERK 1/2 signaling.
AB  - Dithiocarbamate has been tested for its effective anti-tumor activity, but the
      underlying mechanism remains unclear. We previously prepared a novel
      diththiocarbamate derivative, DpdtC with an ability of catalase inhibition. Here,
      we for the first time investigated the growth inhibition effects of DpdtC on HER2
      amplified cancer cells and elucidated its mechanism of action. Results showed
      that DpdtC exerted the potent anti-tumor effects against HER2-overexpressed SK-OV
      3 and SK-BR-3 cells, especially on SK-OV-3 cells with a higher NDRG1 level, which
      was also confirmed in the SK-OV-3 xenograft model. Interestingly, we observed
      that NDRG1 was up-regulated, while membrane expression of HER2 was regressed in
      SK-OV-3 cells upon DpdtC treatment. In agreement, silencing endogenous NDRG1 also
      increased the expression of HER2 in SK-OV-3 cells, while overexpressing NDRG1
      decreased HER2 expression in SK-BR-3 cells. Furthermore, our results showed the
      formation of the EGFR/HER2 heterodimer was attenuated and phosphorylation of
      ERK1/2 was inhibited in SK-OV-3 cells when treated with DpdtC. Collectively,
      these observations demonstrated that NDRG1 plays an important role in mediating
      the inhibition effects of DpdtC in HER2-overexpressed cancer cells via selective
      targeting of the HER2-ERK1/2 pathway. Hence, our investigation suggests that up
      regulation of NDRG1 by DpdtC is a promising therapeutic approach in HER2
      overexpressed cancers.

PMID- 29467386
TI  - BMI reduction and vitamin D insufficiency mediated osteoporosis and fragility
      fractures in patients at nutritional risk: a cross-sectional study.
AB  - It seemed to be common sense that malnutrition was associated with osteoporosis,
      but there were few studies with detailed data proving that. Additionally, the
      association between BMI and osteoporosis was still under discussion. In our study
      of 138 patients, we first confirmed the association between nutrition and
      osteoporosis with propensity score matching method reducing the confounding bias,
      then discovered that body mass index (BMI) and 25OHD level acted as two crucial
      factors of nutrition risk-mediated osteoporosis. Moreover, a new BMI
      classification was proposed in our article to do more help for nutrition
      management and anti-osteoporosis treatment for the old in China. Consequently,
      nutrition is important to bone health, with BMI and 25OHD level playing key
      roles.

PMID- 29467387
TI  - Clinical Utility Gene Card for: Becker muscular dystrophy.

PMID- 29467388
TI  - A novel MAP3K7 splice mutation causes cardiospondylocarpofacial syndrome with
      features of hereditary connective tissue disorder.
AB  - Heterozygous variants in MAP3K7, encoding the transforming growth factor-beta
      activated kinase 1 (TAK1), are associated with the ultrarare
      cardiospondylocarpofacial syndrome (CSCFS). Specific gain-of-function variants in
      the same gene cause the allelic frontometaphyseal dysplasia type 2. Phenotypic
      series of frontometaphyseal dysplasia also comprise variants in FLNA (type 1) and
      two patients with a heterozygous variant in TAB2 (type 3). We report on a 7-year
      old girl with CSCFS due to the novel heterozygous c.737-7A>G variant in MAP3K7.
      The identified variant generates a new splice acceptor site causing an in-frame
      insertion of 2 amino acid residues (p.Asn245_Gly246insValVal), as demonstrated by
      RNA study. The patient was originally ascertained for a presumed hereditary
      connective tissue disorder due to soft/dystrophic skin, extreme joint
      hypermobility, polyvalvular heart disease, and upper gastrointestinal
      dismotility. Our study confirms locus homogeneity for CSCFS, expands the
      mutational spectrum of MAP3K7, and adds data on the existence of a community of
      connective tissue disorders caused by abnormalities of the TAK1-dependent
      signaling pathway.

PMID- 29467389
TI  - Long glucocorticoid-induced leucine zipper regulates human thyroid cancer cell
      proliferation.
AB  - Long glucocorticoid-induced leucine zipper (L-GILZ) has recently been implicated
      in cancer cell proliferation. Here, we investigated its role in human thyroid
      cancer cells. L-GILZ protein was highly expressed in well-differentiated cancer
      cells from thyroid cancer patients and differentiated thyroid cancer cell lines,
      but poorly expressed in anaplastic tumors. A fusion protein containing L-GILZ,
      when overexpressed in an L-GILZ-deficient 8505C cell line derived from
      undifferentiated human thyroid cancer tissue, inhibited cellular proliferation in
      vitro. In addition, when this protein was injected into nude mice, in which cells
      from line 8505C had been transplanted, xenograft growth was reduced. Since the
      mitogen-activated protein kinase (MAPK) pathway is frequently hyperactivated in
      thyroid cancer cells as a result of the BRAFV600E or Ras mutation, we sought to
      further investigate the role of L-GILZ in the MAPK pathway. To this end, we
      analyzed L-GILZ expression and function in cells treated with MAPK inhibitors. We
      used 8505C cells, which have the BRAFV600E mutation, or the CAL-62 cell line,
      which harbors a Ras mutation. The cells were treated with the BRAF-specific drug
      vemurafenib (PLX4032) or the MEK1/2 inhibitor, U0126, respectively. Treatment
      with these agents inhibited MAPK activation, reduced cell proliferation, and
      upregulated L-GILZ expression. L-GILZ silencing reversed the antiproliferative
      activity of the MAPK inhibitors, consistent with an antiproliferative role.
      Treatment with MAPK inhibitors led to the phosphorylation of the cAMP/response
      element-binding protein (CREB), and active CREB bound to the L-GILZ promoter,
      contributing to its transcription. We suggest that the CREB signaling pathway,
      frequently deregulated in thyroid tumors, is involved in L-GILZ upregulation and
      that L-GILZ regulates thyroid cancer cell proliferation, which may have potential
      in cancer treatment.

PMID- 29467390
TI  - FGF1 induces resistance to chemotherapy in ovarian granulosa tumor cells through
      regulation of p53 mitochondrial localization.
AB  - Ovarian cancer remains associated with a high mortality rate and relapse is too
      frequently seen after chemotherapeutic treatment of granulosa cell tumors (GCTs)
      or epithelial ovarian cancers (EOCs). It is thus of major importance to progress
      in the knowledge of the molecular mechanisms underlying chemoresistance of
      ovarian tumors. Overexpression of Fibroblast Growth Factor 1 (FGF1) is observed
      in various cancers, correlates with poor survival and could be responsible for
      resistance to platinum-based chemotherapy of serous ovarian cancers. How FGF1
      promotes escape to chemotherapy remains unknown. In previous studies, we showed
      that FGF1 inhibits p53 transcriptional activities, leading to increased cell
      survival of neuronal or fibroblast cell lines. In this study, we show that FGF1
      favors survival of COV434 cells upon treatment with etoposide and cisplatin, two
      common chemotherapeutic molecules used for ovarian cancer. Etoposide and
      cisplatin induced mitochondrial depolarization, cytochrome c release and caspase
      activation in COV434 cells. Overexpression of FGF1 counteracts these events and
      thus allows increased survival of ovarian cells. In this study, FGF1 had little
      effect on p53 stability and transcriptional activities. Etoposide induced p21
      expression as expected, but p21 protein levels were even increased in the
      presence of FGF1. Using RNA interference, we showed that p21 exerts an anti
      apoptotic activity in COV434 cells. However abrogating this activity was not
      sufficient to restore cell death of FGF1-overexpressing cells. We also show for
      the first time that p53 mitochondrial pathway is involved in the cell death of
      COV434 cells. Indeed, p53 accumulates at mitochondria upon etoposide treatment
      and inhibition of p53 mitochondrial localization using pifithrin-u inhibits
      apoptosis of COV434 cells. FGF1 also decreases mitochondrial accumulation of p53
      induced by etoposide. This constitutes a novel mechanism of action for FGF1 to
      promote cell survival in response to chemotherapy.

PMID- 29467391
TI  - Bio-inspired counter-current multiplier for enrichment of solutes.
AB  - Improving the efficiency of gas separation technology is a challenge facing
      modern industry, since existing methods for gas separation, including hollow
      fiber membrane contactors, vacuum swing adsorption, and cryogenic distillation,
      represents a significant portion of the world's energy consumption. Here, we
      report an enhancement in the release rate of carbon dioxide and oxygen of a
      thermal swing gas desorption unit using a counter-current amplification method
      inspired by fish. Differing from a conventional counter-current extraction
      system, counter-current amplification makes use of parallel capture fluid
      channels separated by a semipermeable membrane in addition to the semipermeable
      membrane separating the capture fluid channel and the gas release channel. The
      membrane separating the incoming and outgoing fluid channels allows gas that
      would normally exit the system to remain in the desorption unit. We demonstrate
      the system using both resistive heating and photothermal heating. With resistive
      heating, an increase in release rate of 240% was observed compared to an
      equivalent counter-current extraction system.

PMID- 29467392
TI  - Alcohol Impairs N100 Response to Dorsolateral Prefrontal Cortex Stimulation.
AB  - Alcohol is thought to exert its effect by acting on gamma-aminobutyric (GABA)
      inhibitory neurotransmission. The N100, the negative peak on
      electroencephalography (EEG) that occurs approximately 100 ms following the
      transcranial magnetic stimulation (TMS) pulse, is believed to represent GABAB
      receptor mediated neurotransmission. However, no studies have examined the effect
      of alcohol on the N100 response to TMS stimulation of the dorsolateral prefrontal
      cortex (DLPFC). In the present study, we aimed to explore the effect of alcohol
      on the DLPFC TMS-evoked N100 response. The study was a within-subject cross-over
      design study. Fifteen healthy alcohol drinkers were administered TMS to the DLPFC
      before (PreBev) and after consumption (PostBev) of an alcohol or placebo
      beverage. The amplitude of the N100 before and after beverage was compared for
      both the alcohol and placebo beverage. Alcohol produced a significant decrease in
      N100 amplitude (t = 4.316, df = 14, p = 0.001). The placebo beverage had no
      effect on the N100 amplitude (t = -1.856, df = 14, p = 0.085). Acute alcohol
      consumption produces a decrease in N100 amplitude to TMS stimulation of the
      DLPFC, suggesting a decrease in GABAB receptor mediated neurotransmission.
      Findings suggest that the N100 may represent a marker of alcohol's effects on
      inhibitory neurotransmission.

PMID- 29467393
TI  - A low cost and high performance polymer donor material for polymer solar cells.
AB  - The application of polymer solar cells requires the realization of high
      efficiency, high stability, and low cost devices. Here we demonstrate a low-cost
      polymer donor poly[(thiophene)-alt-(6,7-difluoro-2-(2-hexyldecyloxy)quinoxaline)]
      (PTQ10), which is synthesized with high overall yield of 87.4% via only two-step
      reactions from cheap raw materials. More importantly, an impressive efficiency of
      12.70% is obtained for the devices with PTQ10 as donor, and the efficiency of the
      inverted structured PTQ10-based device also reaches 12.13% (certificated to be
      12.0%). Furthermore, the as-cast devices also demonstrate a high efficiency of
      10.41% and the devices exhibit insensitivity of active layer thickness from 100
      nm to 300 nm, which is conductive to the large area fabrication of the devices.
      In considering the advantages of low cost and high efficiency with thickness
      insensitivity, we believe that PTQ10 will be a promising polymer donor for
      commercial application of polymer solar cells.

PMID- 29467394
TI  - Development of a high-throughput assay for rapid screening of butanologenic
      strains.
AB  - We report a Thermotoga hypogea (Th) alcohol dehydrogenase (ADH)-dependent
      spectrophotometric assay for quantifying the amount of butanol in growth media,
      an advance that will facilitate rapid high-throughput screening of hypo- and
      hyper-butanol-producing strains of solventogenic Clostridium species. While a
      colorimetric nitroblue tetrazolium chloride-based assay for quantitating butanol
      in acetone-butanol-ethanol (ABE) fermentation broth has been described
      previously, we determined that Saccharomyces cerevisiae (Sc) ADH used in this
      earlier study exhibits approximately 13-fold lower catalytic efficiency towards
      butanol than ethanol. Any Sc ADH-dependent assay for primary quantitation of
      butanol in an ethanol-butanol mixture is therefore subject to "ethanol
      interference". To circumvent this limitation and better facilitate identification
      of hyper-butanol-producing Clostridia, we searched the literature for native ADHs
      that preferentially utilize butanol over ethanol and identified Th ADH as a
      candidate. Indeed, recombinant Th ADH exhibited a 6-fold higher catalytic
      efficiency with butanol than ethanol, as measured using the reduction of NADP+ to
      NADPH that accompanies alcohol oxidation. Moreover, the assay sensitivity was not
      affected by the presence of acetone, acetic acid or butyric acid (typical ABE
      fermentation products). We broadened the utility of our assay by adapting it to a
      high-throughput microtiter plate-based format, and piloted it successfully in an
      ongoing metabolic engineering initiative.

PMID- 29467395
TI  - Spatial geometry of stem cell proliferation in the adult hippocampus.
AB  - The modes of stem cell divisions (e.g., symmetric vs. asymmetric) can have a
      profound impact on the number of progeny and tissue growth, repair, and function.
      This is particularly relevant for adult neural stem cells, since stem cell
      derived neurons affect cognitive and mental states, resistance to stress and
      disease, and response to therapies. Here we show that although dividing stem
      cells in the adult hippocampus display a certain bias towards paired distribution
      (which could imply the prevalence of symmetric divisions), this bias already
      exists in the distribution of the general population of stem cells and may be
      responsible for the perceived occurrence of symmetric stem cell divisions.
      Remarkably, the bias in the distribution of stem cells decreases with age. Our
      results argue that the preexisting bias in stem cell distribution may affect
      current assumptions regarding stem cell division and fate as well as conjectures
      on the prospects of brain repair and rejuvenation.

PMID- 29467396
TI  - Trace metals from historical mining sites and past metallurgical activity remain
      bioavailable to wildlife today.
AB  - Throughout history, ancient human societies exploited mineral resources all over
      the world, even in areas that are now protected and considered to be relatively
      pristine. Here, we show that past mining still has an impact on wildlife in some
      French protected areas. We measured cadmium, copper, lead, and zinc
      concentrations in topsoils and wood mouse kidneys from sites located in the
      Cevennes and the Morvan. The maximum levels of metals in these topsoils are one
      or two orders of magnitude greater than their commonly reported mean values in
      European topsoils. The transfer to biota was effective, as the lead concentration
      (and to a lesser extent, cadmium) in wood mouse kidneys increased with soil
      concentration, unlike copper and zinc, providing direct evidence that lead
      emitted in the environment several centuries ago is still bioavailable to free
      ranging mammals. The negative correlation between kidney lead concentration and
      animal body condition suggests that historical mining activity may continue to
      play a role in the complex relationships between trace metal pollution and body
      indices. Ancient mining sites could therefore be used to assess the long-term
      fate of trace metals in soils and the subsequent risks to human health and the
      environment.

PMID- 29467397
TI  - Expanded diversity of microbial groups that shape the dissimilatory sulfur cycle.
AB  - A critical step in the biogeochemical cycle of sulfur on Earth is microbial
      sulfate reduction, yet organisms from relatively few lineages have been
      implicated in this process. Previous studies using functional marker genes have
      detected abundant, novel dissimilatory sulfite reductases (DsrAB) that could
      confer the capacity for microbial sulfite/sulfate reduction but were not
      affiliated with known organisms. Thus, the identity of a significant fraction of
      sulfate/sulfite-reducing microbes has remained elusive. Here we report the
      discovery of the capacity for sulfate/sulfite reduction in the genomes of
      organisms from 13 bacterial and archaeal phyla, thereby more than doubling the
      number of microbial phyla associated with this process. Eight of the 13 newly
      identified groups are candidate phyla that lack isolated representatives, a
      finding only possible given genomes from metagenomes. Organisms from
      Verrucomicrobia and two candidate phyla, Candidatus Rokubacteria and Candidatus
      Hydrothermarchaeota, contain some of the earliest evolved dsrAB genes. The
      capacity for sulfite reduction has been laterally transferred in multiple events
      within some phyla, and a key gene potentially capable of modulating sulfur
      metabolism in associated cells has been acquired by putatively symbiotic
      bacteria. We conclude that current functional predictions based on phylogeny
      significantly underestimate the extent of sulfate/sulfite reduction across
      Earth's ecosystems. Understanding the prevalence of this capacity is integral to
      interpreting the carbon cycle because sulfate reduction is often coupled to
      turnover of buried organic carbon. Our findings expand the diversity of microbial
      groups associated with sulfur transformations in the environment and motivate
      revision of biogeochemical process models based on microbial community
      composition.

PMID- 29467398
TI  - A virus or more in (nearly) every cell: ubiquitous networks of virus-host
      interactions in extreme environments.
AB  - The application of viral and cellular metagenomics to natural environments has
      expanded our understanding of the structure, functioning, and diversity of
      microbial and viral communities. The high diversity of many communities, e.g.,
      soils, surface ocean waters, and animal-associated microbiomes, make it difficult
      to establish virus-host associations at the single cell (rather than population)
      level, assign cellular hosts, or determine the extent of viral host range from
      metagenomics studies alone. Here, we combine single-cell sequencing with
      environmental metagenomics to characterize the structure of virus-host
      associations in a Yellowstone National Park (YNP) hot spring microbial community.
      Leveraging the relatively low diversity of the YNP environment, we are able to
      overlay evidence at the single-cell level with contextualized viral and cellular
      community structure. Combining evidence from hexanucelotide analysis, single cell
      read mapping, network-based analytics, and CRISPR-based inference, we
      conservatively estimate that >60% of cells contain at least one virus type and a
      majority of these cells contain two or more virus types. Of the detected virus
      types, nearly 50% were found in more than 2 cellular clades, indicative of a
      broad host range. The new lens provided by the combination of metaviromics and
      single-cell genomics reveals a network of virus-host interactions in extreme
      environments, provides evidence that extensive virus-host associations are
      common, and further expands the unseen impact of viruses on cellular life.

PMID- 29467399
TI  - Assessment of novel vaccination regimens using viral vectored liver stage malaria
      vaccines encoding ME-TRAP.
AB  - Heterologous prime-boost vaccination with viral vectors simian adenovirus 63
      (ChAd63) and Modified Vaccinia Ankara (MVA) induces potent T cell and antibody
      responses in humans. The 8-week regimen demonstrates significant efficacy against
      malaria when expressing the pre-erythrocytic malaria antigen Thrombospondin
      Related Adhesion Protein fused to a multiple epitope string (ME-TRAP). We tested
      these vaccines in 7 new 4- and 8- week interval schedules to evaluate safety and
      immunogenicity of multiple ChAd63 ME-TRAP priming vaccinations (denoted A),
      multiple MVA ME-TRAP boosts (denoted M) and alternating vectors. All regimens
      exhibited acceptable reactogenicity and CD8+ T cell immunogenicity was enhanced
      with a 4-week interval (AM) and with incorporation of additional ChAd63 ME-TRAP
      vaccination at 4- or 8-weeks (AAM or A_A_M). Induction of TRAP antibodies was
      comparable between schedules. T cell immunity against the ChAd63 hexon did not
      affect T cell responses to the vaccine insert, however pre-vaccination ChAd63
      specific T cells correlated with reduced TRAP antibodies. Vaccine-induced
      antibodies against MVA did not affect TRAP antibody induction, and correlated
      positively with ME-TRAP-specific T cells. This study identifies potentially more
      effective immunisation regimens to assess in Phase IIa trials and demonstrates a
      degree of flexibility with the timing of vectored vaccine administration, aiding
      incorporation into existing vaccination programmes.

PMID- 29467400
TI  - A Saliva Protein of Varroa Mites Contributes to the Toxicity toward Apis cerana
      and the DWV Elevation in A. mellifera.
AB  - Varroa destructor mites express strong avoidance of the Apis cerana worker brood
      in the field. The molecular mechanism for this phenomenon remains unknown. We
      identified a Varroa toxic protein (VTP), which exhibited toxic activity toward A.
      cerana worker larvae, in the saliva of these mites, and expressed VTP in an
      Escherichia coli system. We further demonstrated that recombinant VTP killed A.
      cerana worker larvae and pupae in the absence of deformed-wing virus (DWV) but
      was not toxic to A. cerana worker adults and drones. The recombinant VTP was safe
      for A. mellifera individuals, but resulted in elevated DWV titers and the
      subsequent development of deformed-wing adults. RNAi-mediated suppression of vtp
      gene expression in the mites partially protected A. cerana larvae. We propose a
      modified mechanism for Varroa mite avoidance of worker brood, due to mutual
      destruction stress, including the worker larvae blocking Varroa mite reproduction
      and Varroa mites killing worker larvae by the saliva toxin. The discovery of VTP
      should provide a better understanding of Varroa pathogenesis, facilitate host
      parasite mechanism research and allow the development of effective methods to
      control these harmful mites.

PMID- 29467401
TI  - dynGENIE3: dynamical GENIE3 for the inference of gene networks from time series
      expression data.
AB  - The elucidation of gene regulatory networks is one of the major challenges of
      systems biology. Measurements about genes that are exploited by network inference
      methods are typically available either in the form of steady-state expression
      vectors or time series expression data. In our previous work, we proposed the
      GENIE3 method that exploits variable importance scores derived from Random
      forests to identify the regulators of each target gene. This method provided
      state-of-the-art performance on several benchmark datasets, but it could however
      not specifically be applied to time series expression data. We propose here an
      adaptation of the GENIE3 method, called dynamical GENIE3 (dynGENIE3), for
      handling both time series and steady-state expression data. The proposed method
      is evaluated extensively on the artificial DREAM4 benchmarks and on three real
      time series expression datasets. Although dynGENIE3 does not systematically yield
      the best performance on each and every network, it is competitive with diverse
      methods from the literature, while preserving the main advantages of GENIE3 in
      terms of scalability.

PMID- 29467402
TI  - Development of a model predicting non-satisfaction 1 year after primary total
      knee replacement in the UK and transportation to Switzerland.
AB  - We aimed to develop a predictive model for non-satisfaction following primary
      total knee replacement (TKR) and to assess its transportability to another health
      care system. Data for model development were obtained from two UK tertiary
      hospitals. Model transportation data were collected from Geneva University
      Hospitals in Switzerland. Participants were individuals undergoing primary TKR
      with non-satisfaction with surgery after one year the outcome of interest.
      Multiple imputation and logistic regression modelling with bootstrap backward
      selection were used to identify predictors of outcome. Model performance was
      assessed by discrimination and calibration. 64 (14.2%) patients in the UK and 157
      (19.9%) in Geneva were non-satisfied with their TKR. Predictors in the UK cohort
      were worse pre-operative pain and function, current smoking, treatment for
      anxiety and not having been treated with injected corticosteroids (corrected AUC
      = 0.65). Transportation to the Geneva cohort showed an AUC of 0.55. Importantly,
      two UK predictors (treated for anxiety, injected corticosteroids) were not
      predictive in Geneva. A better model fit was obtained when coefficients were re
      estimated in the Geneva sample (AUC = 0.64). The model did not perform well when
      transported to a different country, but improved when it was re-estimated. This
      emphasises the need to re-validate the model for each setting/country.

PMID- 29467403
TI  - Proteome analysis of Aspergillus flavus isolate-specific responses to oxidative
      stress in relationship to aflatoxin production capability.
AB  - Aspergillus flavus is an opportunistic pathogen of plants such as maize and
      peanut under conducive conditions such as drought stress resulting in significant
      aflatoxin production. Drought-associated oxidative stress also exacerbates
      aflatoxin production by A. flavus. The objectives of this study were to use
      proteomics to provide insights into the pathogen responses to H2O2-derived
      oxidative stress, and to identify potential biomarkers and targets for host
      resistance breeding. Three isolates, AF13, NRRL3357, and K54A with high,
      moderate, and no aflatoxin production, were cultured in medium supplemented with
      varying levels of H2O2, and examined using an iTRAQ (Isobaric Tags for Relative
      and Absolute Quantification) approach. Overall, 1,173 proteins were identified
      and 220 were differentially expressed (DEPs). Observed DEPs encompassed metabolic
      pathways including antioxidants, carbohydrates, pathogenicity, and secondary
      metabolism. Increased lytic enzyme, secondary metabolite, and developmental
      pathway expression in AF13 was correlated with oxidative stress tolerance, likely
      assisting in plant infection and microbial competition. Elevated expression of
      energy and cellular component production in NRRL3357 and K54A implies a focus on
      oxidative damage remediation. These trends explain isolate-to-isolate variation
      in oxidative stress tolerance and provide insights into mechanisms relevant to
      host plant interactions under drought stress allowing for more targeted efforts
      in host resistance research.

PMID- 29467405
TI  - MUC13 contributes to rewiring of glucose metabolism in pancreatic cancer.
AB  - Pancreatic tumors are rewired for high-glucose metabolism and typically present
      with exceptionally poor prognosis. Recently, we have shown that MUC13, which is
      highly expressed in pancreatic tumors, promotes tumor progression via modulation
      of HER2 receptor tyrosine kinase activity. Herein, we investigate a novel, MUC13
      mediated molecular mechanism responsible for higher glucose metabolism in
      pancreatic tumors. Our results demonstrate that MUC13 expression leads to the
      activation/nuclear translocation of NF-kappaB p65 and phosphorylation of IkappaB,
      which in turn upregulates the expression of important proteins (Glut-1, c-Myc,
      and Bcl-2) that are involved in glucose metabolism. MUC13 functionally interacts
      and stabilizes Glut-1 to instigate downstream events responsible for higher
      glucose uptake in pancreatic cancer cells. Altered MUC13 expression by
      overexpression and knockdown techniques effectively modulated glucose uptake,
      lactate secretion, and metastatic phenotypes in pancreatic cancer cells. NF
      kappaB inhibitor, Sulfasalazine, abrogates the MUC13 and Glut-1 interaction, and
      attenuates events associated with MUC13-induced glucose metabolism. Pancreatic
      ductal adenocarcinoma (PDAC) patient tissue samples also show a positive
      correlation between the expression of these two proteins. These results delineate
      how MUC13 rewire aberrant glucose metabolism to enhance aggressiveness of
      pancreatic cancer and revealed a novel mechanism to develop newer therapeutic
      strategies for this exceptionally difficult cancer.

PMID- 29467404
TI  - Basal condensation of Numb and Pon complex via phase transition during Drosophila
      neuroblast asymmetric division.
AB  - Uneven distribution and local concentration of protein complexes on distinct
      membrane cortices is a fundamental property in numerous biological processes,
      including Drosophila neuroblast (NB) asymmetric cell divisions and cell polarity
      in general. In NBs, the cell fate determinant Numb forms a basal crescent
      together with Pon and is segregated into the basal daughter cell to initiate its
      differentiation. Here we discover that Numb PTB domain, using two distinct
      binding surfaces, recognizes repeating motifs within Pon in a previously
      unrecognized mode. The multivalent Numb-Pon interaction leads to high binding
      specificity and liquid-liquid phase separation of the complex. Perturbations of
      the Numb/Pon complex phase transition impair the basal localization of Numb and
      its subsequent suppression of Notch signaling during NB asymmetric divisions.
      Such phase-transition-mediated protein condensations on distinct membrane
      cortices may be a general mechanism for various cell polarity regulatory
      complexes.

PMID- 29467406
TI  - Genetic variations in ARE1 mediate grain yield by modulating nitrogen utilization
      in rice.
AB  - In crops, nitrogen directly determines productivity and biomass. However, the
      improvement of nitrogen utilization efficiency (NUE) is still a major challenge
      in modern agriculture. Here, we report the characterization of are1, a genetic
      suppressor of a rice fd-gogat mutant defective in nitrogen assimilation. ARE1 is
      a highly conserved gene, encoding a chloroplast-localized protein. Loss-of
      function mutations in ARE1 cause delayed senescence and result in 10-20% grain
      yield increases, hence enhance NUE under nitrogen-limiting conditions. Analysis
      of a panel of 2155 rice varieties reveals that 18% indica and 48% aus accessions
      carry small insertions in the ARE1 promoter, which result in a reduction in ARE1
      expression and an increase in grain yield under nitrogen-limiting conditions. We
      propose that ARE1 is a key mediator of NUE and represents a promising target for
      breeding high-yield cultivars under nitrogen-limiting condition.

PMID- 29467407
TI  - Maternal obesity-induced decreases in plasma, hepatic and uterine polyunsaturated
      fatty acids during labour is reversed through improved nutrition at conception.
AB  - Maternal obesity is associated with prolonged and dysfunctional labour,
      potentially through decreased synthesis of prostaglandins that stimulate
      myometrial contractions. We assessed the impact of maternal obesity on
      concentrations of precursor fatty acids (FA) for prostaglandin synthesis and
      whether any changes could be reversed by improved nutrition post-conception.
      Wistar rats were fed control (CON) or High-Fat, High-cholesterol (HFHC) diets 6
      weeks before mating. At conception half the dams switched diets providing 4
      dietary groups: (1) CON, (2) HFHC, (3) CON-HFHC or (4) HFHC-CON. During
      parturition rats were euthanized and FA composition of plasma, liver and uterus
      determined. Visceral fat was doubled in rats exposed to the HFHC diet prior to
      and/or during pregnancy compared to CON. HFHC diet increased MUFAs but decreased
      omega-3 and omega-6 PUFAs in plasma and liver. Uterine omega-3 FA concentrations
      were halved in HFHC versus CON rats, but all other FAs were similar. Switching
      from HFHC to CON diet at conception restored all FA profiles to those seen in CON
      rats. The increased MUFA and decreased PUFA concentrations in obese HFHC dams may
      contribute to aberrant prostaglandin synthesis and dysfunctional myometrial
      activity and it may be possible to reverse these changes, and potentially improve
      labour outcomes, by improving nutrition at conception.

PMID- 29467409
TI  - Combined use of CEMIP and CA 19-9 enhances diagnostic accuracy for pancreatic
      cancer.
AB  - Carbohydrate antigen (CA) 19-9 is the only diagnostic marker used in pancreatic
      cancer despite its limitations. Here, we aimed to identify the diagnostic role of
      CEMIP (also called KIAA1199) combined with CA 19-9 in patients with pancreatic
      cancer. A retrospective analysis of prospectively collected patient samples was
      performed to determine the benefit of diagnostic markers in the diagnosis of
      pancreatic cancer. We investigated CEMIP and CA 19-9 levels in 324 patients with
      pancreatic cancer and 49 normal controls using serum enzyme-linked immunosorbent
      assay. Median CA 19-9 and CEMIP levels were 410.5 U/ml (40.8-3342.5) and 0.67
      ng/ml (0.40-1.08), respectively, in patients with pancreatic cancer. The AUROC
      for CA 19-9 and CEMIP were 0.847 (95% confidence interval [CI]: 0.806-0.888) and
      0.760 (95% CI: 0.689-0.831), respectively. Combination of CA 19-9 with CEMIP
      showed markedly improved AUROC over CA 19-9 alone in pancreatic cancer diagnosis
      (0.94 vs. 0.89; P < 0.0001). CEMIP showed a diagnostic yield of 86.1% (68/79) in
      CA 19-9 negative pancreatic cancer. Combined use with CEMIP showed significantly
      improved diagnostic value compared with CA 19-9 alone in pancreatic cancer.
      Especially, CEMIP may be a complementary marker in pancreatic cancer patients
      with normal CA 19-9 levels.

PMID- 29467408
TI  - Prediction complements explanation in understanding the developing brain.
AB  - A central aim of human neuroscience is understanding the neurobiology of
      cognition and behavior. Although we have made significant progress towards this
      goal, reliance on group-level studies of the developed adult brain has limited
      our ability to explain population variability and developmental changes in neural
      circuitry and behavior. In this review, we suggest that predictive modeling, a
      method for predicting individual differences in behavior from brain features, can
      complement descriptive approaches and provide new ways to account for this
      variability. Highlighting the outsized scientific and clinical benefits of
      prediction in developmental populations including adolescence, we show that
      predictive brain-based models are already providing new insights on adolescent
      specific risk-related behaviors. Together with large-scale developmental
      neuroimaging datasets and complementary analytic approaches, predictive modeling
      affords us the opportunity and obligation to identify novel treatment targets and
      individually tailor the course of interventions for developmental
      psychopathologies that impact so many young people today.

PMID- 29467410
TI  - Analysis of cardiomyocyte clonal expansion during mouse heart development and
      injury.
AB  - The cellular mechanisms driving cardiac tissue formation remain poorly
      understood, largely due to the structural and functional complexity of the heart.
      It is unclear whether newly generated myocytes originate from cardiac
      stem/progenitor cells or from pre-existing cardiomyocytes that re-enter the cell
      cycle. Here, we identify the source of new cardiomyocytes during mouse
      development and after injury. Our findings suggest that cardiac progenitors
      maintain proliferative potential and are the main source of cardiomyocytes during
      development; however, the onset of alphaMHC expression leads to reduced cycling
      capacity. Single-cell RNA sequencing reveals a proliferative, "progenitor-like"
      population abundant in early embryonic stages that decreases to minimal levels
      postnatally. Furthermore, cardiac injury by ligation of the left anterior
      descending artery was found to activate cardiomyocyte proliferation in neonatal
      but not adult mice. Our data suggest that clonal dominance of differentiating
      progenitors mediates cardiac development, while a distinct subpopulation of
      cardiomyocytes may have the potential for limited proliferation during late
      embryonic development and shortly after birth.

PMID- 29467411
TI  - The impact of unrecorded readings on the precision and diagnostic performance of
      home blood pressure monitoring: a statistical study.
AB  - Hypertension is a major cardiovascular risk factor. To address the disease
      adequately, most clinicians rely on home blood pressure monitoring (HBPM).
      However, the impact of unrecorded BP values on the precision and diagnostic
      performance of BP schedules is unknown. We obtained 103 HBP patients schedules
      from a previous study. Then, readings were randomly removed from each schedule in
      order to create new incomplete schedules using a resampling technique. We
      obtained 10,000 new incomplete schedules. For each number of randomly removed
      readings, the percentages of incomplete schedules outside a systolic/diastolic
      blood pressure (SBP/DBP) range of 5/3 mmHg were calculated from the same complete
      patient's schedule. The sensitivity and specificity of incomplete HBPM schedules
      regarding BP control were also assessed. One hundred three HBPM schedules were
      analyzed. Mean patients' age was 67.9 +/- 9.9 years. In non-diabetic patients,
      the mean BP of complete schedules' means was 131.9 +/- 12.4/75.5 +/- 10.5. In
      diabetic patients, the mean BP of complete schedules' means was 135.5 +/-
      14.0/73.4 +/- 8.2 mmHg. When schedules were composed of 14 and 21 random
      measures, differences over 5 mmHg were seen in 2.6% and 0.1% of non-diabetic
      patients' schedule and 3.7% and 0.1% of diabetic patients' schedule,
      respectively. At 21 measurements, sensitivity and specificity were approximately
      95% and 98% in non-diabetic patients and 90% and 99% in non-diabetic patients,
      respectively. HBPM precision and diagnostic performance improve rapidly with
      accumulation of readings. Incomplete schedules composed of 21 readings can
      provide an almost perfect diagnostic tool compared with the complete schedule
      reference.

PMID- 29467412
TI  - IL-32 gamma reduces lung tumor development through upregulation of TIMP-3
      overexpression and hypomethylation.
AB  - The low expression of tissue inhibitor of metalloproteinase 3 (TIMP-3) is
      important in inflammatory responses. Therefore, inhibition of TIMP-3 may promote
      tumor development. Our study showed that expression of TIMP-3 was elevated in lL
      32gamma mice lung tissues. In this study, we investigated whether IL-32gamma mice
      inhibited lung tumor development through overexpression of TIMP-3 and its
      methylation. To explore the possible underlying mechanism, lung cancer cells were
      transfected with IL-32gamma cDNA plasmid. A marked increase in TIMP-3 expression
      was caused by promoter methylation. Mechanistic studies indicated that TIMP-3
      overexpression reduced NF-kappaB activity, which led to cell growth inhibition in
      IL-32gamma transfected lung cancer cells. We also showed that IL-32gamma inhibits
      expression of DNA (cytosine-5-)-methyltransferase 1 (DNMT1). Moreover, IL-32gamma
      inhibits the binding of DNMT1 to TIMP-3 promoter, but this effect was reversed by
      the treatment of DNA methyltransferase inhibitor (5-Aza-CdR) and NF-kappaB
      inhibitor (PS1145), suggesting that a marked increase in TIMP-3 expression was
      caused by inhibition of promoter hypermethylation via decreased DNMT1 expression
      through the NF-kappaB pathway. In an in vivo carcinogen induced lung tumor model,
      tumor growth was inhibited in IL-32gamma overexpressed mice with elevated TIMP-3
      expression and hypomethylation accompanied with reduced NF-kappaB activity.
      Moreover, in the lung cancer patient tissue, the expression of IL-32 and TIMP-3
      was dramatically decreased at a grade-dependent manner compared to normal lung
      tissue. In summary, IL-32gamma may increase TIMP-3 expression via hypomethylation
      through inactivation of NF-kappaB activity, and thereby reduce lung tumor growth.

PMID- 29467413
TI  - Tunable Mechanical Metamaterials through Hybrid Kirigami Structures.
AB  - Inspired by the art of paper cutting, kirigami provides intriguing tools to
      create materials with unconventional mechanical and morphological responses. This
      behavior is appealing in multiple applications such as stretchable electronics
      and soft robotics and presents a tractable platform to study structure-property
      relationships in material systems. However, mechanical response is typically
      controlled through a single or fractal cut type patterned across an entire
      kirigami sheet, limiting deformation modes and tunability. Here we show how
      hybrid patterns of major and minor cuts creates new opportunities to introduce
      boundary conditions and non-prismatic beams to enable highly tunable mechanical
      responses. This hybrid approach reduces stiffness by a factor of ~30 while
      increasing ultimate strain by a factor of 2 (up to 750% strain) relative to
      single incision patterns. We present analytical models and generate general
      design criteria that is in excellent agreement with experimental data from
      nanoscopic to macroscopic systems. These hybrid kirigami materials create new
      opportunities for multifunctional materials and structures, which we demonstrate
      with stretchable kirigami conductors with nearly constant electrical resistance
      up to >400% strain and magnetoactive actuators with extremely rapid response
      (>10,000% strain s-1) and high, repeatable elongation (>300% strain).

PMID- 29467414
TI  - Induction of long-lived room temperature phosphorescence of carbon dots by water
      in hydrogen-bonded matrices.
AB  - Phosphorescence shows great potential for application in bioimaging and ion
      detection because of its long-lived luminescence and high signal-to-noise ratio,
      but establishing phosphorescence emission in aqueous environments remains a
      challenge. Herein, we present a general design strategy that effectively promotes
      phosphorescence by utilising water molecules to construct hydrogen-bonded
      networks between carbon dots (CDs) and cyanuric acid (CA). Interestingly, water
      molecules not only cause no phosphorescence quenching but also greatly enhance
      the phosphorescence emission. This enhancement behaviour can be explained by the
      fact that the highly ordered bound water on the CA particle surface can construct
      robust bridge-like hydrogen-bonded networks between the CDs and CA, which not
      only effectively rigidifies the C=O bonds of the CDs but also greatly enhances
      the rigidity of the entire system. In addition, the CD-CA suspension exhibits a
      high phosphorescence lifetime (687 ms) and is successfully applied in ion
      detection based on its visible phosphorescence.

PMID- 29467415
TI  - PARP1 and PARP2 stabilise replication forks at base excision repair intermediates
      through Fbh1-dependent Rad51 regulation.
AB  - PARP1 regulates the repair of DNA single-strand breaks generated directly, or
      during base excision repair (BER). However, the role of PARP2 in these and other
      repair mechanisms is unknown. Here, we report a requirement for PARP2 in
      stabilising replication forks that encounter BER intermediates through Fbh1
      dependent regulation of Rad51. Whereas PARP2 is dispensable for tolerance of
      cells to SSBs or homologous recombination dysfunction, it is redundant with PARP1
      in BER. Therefore, combined disruption of PARP1 and PARP2 leads to defective BER,
      resulting in elevated levels of replication-associated DNA damage owing to an
      inability to stabilise Rad51 at damaged replication forks and prevent
      uncontrolled DNA resection. Together, our results demonstrate how PARP1 and PARP2
      regulate two independent, but intrinsically linked aspects of DNA base damage
      tolerance by promoting BER directly, and by stabilising replication forks that
      encounter BER intermediates.

PMID- 29467416
TI  - Long-distance propagation of short-wavelength spin waves.
AB  - Recent years have witnessed a rapidly growing interest in exploring the use of
      spin waves for information transmission and computation toward establishing a
      spin-wave-based technology that is not only significantly more energy efficient
      than the CMOS technology, but may also cause a major departure from the von
      Neumann architecture by enabling memory-in-logic and logic-in-memory
      architectures. A major bottleneck of advancing this technology is the excitation
      of spin waves with short wavelengths, which is a must because the wavelength
      dictates device scalability. Here, we report the discovery of an approach for the
      excitation of nm-wavelength spin waves. The demonstration uses ferromagnetic
      nanowires grown on a 20-nm-thick Y3Fe5O12 film strip. The propagation of spin
      waves with a wavelength down to 50 nm over a distance of 60,000 nm is measured.
      The measurements yield a spin-wave group velocity as high as 2600 m s-1, which is
      faster than both domain wall and skyrmion motions.

PMID- 29467417
TI  - Searching for an exotic spin-dependent interaction with a single electron-spin
      quantum sensor.
AB  - Searching for new particles beyond the standard model is crucial for
      understanding several fundamental conundrums in physics and astrophysics. Several
      hypothetical particles can mediate exotic spin-dependent interactions between
      ordinary fermions, which enable laboratory searches via the detection of the
      interactions. Most laboratory searches utilize a macroscopic source and detector,
      thus allowing the detection of interactions with submillimeter force range and
      above. It remains a challenge to detect the interactions at shorter force ranges.
      Here we propose and demonstrate that a near-surface nitrogen-vacancy center in
      diamond can be utilized as a quantum sensor to detect the monopole-dipole
      interaction between an electron spin and nucleons. Our result sets a constraint
      for the electron-nucleon coupling, [Formula: see text], with the force range 0.1
      23 MUm. The obtained upper bound of the coupling at 20 MUm is [Formula: see text]
      < 6.24 * 10-15.

PMID- 29467418
TI  - Exogenous nitric oxide stimulates the odontogenic differentiation of rat dental
      pulp stem cells.
AB  - Nitric oxide (NO) is thought to play a pivotal regulatory role in dental pulp
      tissues under both physiological and pathological conditions. However, little is
      known about the NO functions in dental pulp stem cells (DPSCs). We examined the
      direct actions of a spontaneous NO gas-releasing donor, NOC-18, on the
      odontogenic capacity of rat DPSCs (rDPSCs). In the presence of NOC-18, rDPSCs
      were transformed into odontoblast-like cells with long cytoplasmic processes and
      a polarized nucleus. NOC-18 treatment increased alkaline phosphatase activity and
      enhanced dentin-like mineralized tissue formation and the expression levels of
      several odontoblast-specific genes, such as runt related factor 2, dentin matrix
      protein 1 and dentin sialophosphoprotein, in rDPSCs. In contrast, carboxy-PTIO, a
      NO scavenger, completely suppressed the odontogenic capacity of rDPSCs. This NO
      promoted odontogenic differentiation was activated by tumor necrosis factor-NF
      kappaB axis in rDPSCs. Further in vivo study demonstrated that NOC-18-application
      in a tooth cavity accelerated tertiary dentin formation, which was associated
      with early nitrotyrosine expression in the dental pulp tissues beneath the
      cavity. Taken together, the present findings indicate that exogenous NO directly
      induces the odontogenic capacity of rDPSCs, suggesting that NO donors might offer
      a novel host DPSC-targeting alternative to current pulp capping agents in
      endodontics.

PMID- 29467420
TI  - Direct DNA and RNA detection from large volumes of whole human blood.
AB  - PCR inhibitors in clinical specimens negatively affect the sensitivity of
      diagnostic PCR and RT-PCR or may even cause false-negative results. To overcome
      PCR inhibition, increase the sensitivity of the assays and simplify the detection
      protocols, simple methods based on quantitative nested real-time PCR and RT-PCR
      were developed to detect exogenous DNA and RNA directly from large volumes of
      whole human blood (WHB). Thermus thermophilus (Tth) polymerase is resistant to
      several common PCR inhibitors and exhibits reverse transcriptase activity in the
      presence of manganese ions. In combination with optimized concentrations of
      magnesium ions and manganese ions, Tth polymerase enabled efficient detection of
      DNA and RNA from large volumes of WHB treated with various anticoagulants. The
      applicability of these methods was further demonstrated by examining WHB
      specimens collected from different healthy individuals and those stored under a
      variety of conditions. The detection limit of these methods was determined by
      detecting exogenous DNA, RNA, and bacteria spiked in WHB. To the best of our
      knowledge, direct RNA detection from large volumes of WHB has not been reported.
      The results of the developed methods can be obtained within 4 hours, making them
      possible for rapid and accurate detection of disease-causing agents from WHB.

PMID- 29467419
TI  - A neuronal mechanism underlying decision-making deficits during hyperdopaminergic
      states.
AB  - Hyperdopaminergic states in mental disorders are associated with disruptive
      deficits in decision making. However, the precise contribution of topographically
      distinct mesencephalic dopamine pathways to decision-making processes remains
      elusive. Here we show, using a multidisciplinary approach, how hyperactivity of
      ascending projections from the ventral tegmental area (VTA) contributes to
      impaired flexible decision making in rats. Activation of the VTA-nucleus
      accumbens pathway leads to insensitivity to loss and punishment due to impaired
      processing of negative reward prediction errors. In contrast, activation of the
      VTA-prefrontal cortex pathway promotes risky decision making without affecting
      the ability to choose the economically most beneficial option. Together, these
      findings show how malfunction of ascending VTA projections affects value-based
      decision making, suggesting a potential mechanism through which increased
      forebrain dopamine signaling leads to aberrant behavior, as is seen in substance
      abuse, mania, and after dopamine replacement therapy in Parkinson's disease.

PMID- 29467421
TI  - Application of kernel principal component analysis and computational machine
      learning to exploration of metabolites strongly associated with diet.
AB  - Computer-based technological innovation provides advancements in sophisticated
      and diverse analytical instruments, enabling massive amounts of data collection
      with relative ease. This is accompanied by a fast-growing demand for
      technological progress in data mining methods for analysis of big data derived
      from chemical and biological systems. From this perspective, use of a general
      "linear" multivariate analysis alone limits interpretations due to "non-linear"
      variations in metabolic data from living organisms. Here we describe a kernel
      principal component analysis (KPCA)-incorporated analytical approach for
      extracting useful information from metabolic profiling data. To overcome the
      limitation of important variable (metabolite) determinations, we incorporated a
      random forest conditional variable importance measure into our KPCA-based
      analytical approach to demonstrate the relative importance of metabolites. Using
      a market basket analysis, hippurate, the most important variable detected in the
      importance measure, was associated with high levels of some vitamins and minerals
      present in foods eaten the previous day, suggesting a relationship between
      increased hippurate and intake of a wide variety of vegetables and fruits.
      Therefore, the KPCA-incorporated analytical approach described herein enabled us
      to capture input-output responses, and should be useful not only for metabolic
      profiling but also for profiling in other areas of biological and environmental
      systems.

PMID- 29467422
TI  - Luminescent and paramagnetic properties of nanoparticles shed light on their
      interactions with proteins.
AB  - Nanoparticles have been recognized as promising tools for targeted drug-delivery
      and protein therapeutics. However, the mechanisms of protein-nanoparticle
      interaction and the dynamics underlying the binding process are poorly
      understood. Here, we present a general methodology for the characterization of
      protein-nanoparticle interaction on a molecular level. To this end we combined
      biophysical techniques including nuclear magnetic resonance (NMR), circular
      dichroism (CD), resonance energy transfer (RET) and surface plasmon resonance
      (SPR). Particularly, we analyzed molecular mechanisms and dynamics of the
      interaction of CaF2 nanoparticles with the prototypical calcium sensor calmodulin
      (CaM). We observed the transient formation of an intermediate encounter complex
      involving the structural region linking the two domains. Specific interaction of
      CaM with CaF2 NPs is driven by the N-terminal EF-hands, which seem to recognize
      Ca2+ on the surface of the nanoparticle. We conclude that CaF2 NP-CaM interaction
      is fully compatible with potential applications in nanomedicine. Overall, the
      methods presented in this work can be extended to other systems and may be useful
      to quantitatively characterize structural and dynamic features of protein-NP
      interactions with important implications for nanomedicine and nano-biotechnology.

PMID- 29467423
TI  - Transcriptome changes induced by abiotic stresses in Artemisia annua.
AB  - Artemisia annua is known to be the source of artemisinin worldwide which is an
      antimalarial compound but is synthesised in very limited amount in the plant.
      Most research laid emphasis on the methods of enhancing artemisinin but our study
      has been planned in a way that it may simultaneously address two problems
      encountered by the plant. Firstly, to know the effect on the artemisinin content
      in the era of climate change because the secondary metabolites tend to increase
      under stress. Secondly, to identify some of the stress responsive genes that
      could help in stress tolerance of the plant under abiotic stress. Hence, the A.
      annua plants were subjected to four abiotic stresses (salt, cold, drought and
      water-logging) and it was observed that the artemisinin content increased in all
      the stress conditions except drought. Next, in order to identify the stress
      responsive genes, the transcriptome sequencing of the plants under stress was
      carried out resulting in 89,362 transcripts for control and 81,328, 76,337,
      90,470 and 96,493 transcripts for salt, cold, drought, and water logging
      stresses. This investigation provides new insights for functional studies of
      genes involved in multiple abiotic stresses and potential candidate genes for
      multiple stress tolerance in A. annua.

PMID- 29467424
TI  - Spin canting across core/shell Fe3O4/MnxFe3-xO4 nanoparticles.
AB  - Magnetic nanoparticles (MNPs) have become increasingly important in biomedical
      applications like magnetic imaging and hyperthermia based cancer treatment.
      Understanding their magnetic spin configurations is important for optimizing
      these applications. The measured magnetization of MNPs can be significantly lower
      than bulk counterparts, often due to canted spins. This has previously been
      presumed to be a surface effect, where reduced exchange allows spins closest to
      the nanoparticle surface to deviate locally from collinear structures. We
      demonstrate that intraparticle effects can induce spin canting throughout a MNP
      via the Dzyaloshinskii-Moriya interaction (DMI). We study ~7.4 nm diameter,
      core/shell Fe3O4/MnxFe3-xO4 MNPs with a 0.5 nm Mn-ferrite shell. Mossbauer
      spectroscopy, x-ray absorption spectroscopy and x-ray magnetic circular dichroism
      are used to determine chemical structure of core and shell. Polarized small angle
      neutron scattering shows parallel and perpendicular magnetic correlations,
      suggesting multiparticle coherent spin canting in an applied field. Atomistic
      simulations reveal the underlying mechanism of the observed spin canting. These
      show that strong DMI can lead to magnetic frustration within the shell and cause
      canting of the net particle moment. These results illuminate how core/shell
      nanoparticle systems can be engineered for spin canting across the whole of the
      particle, rather than solely at the surface.

PMID- 29467425
TI  - Genome-scale examination of NBS-encoding genes in blueberry.
AB  - Blueberry is an important crop worldwide. It is, however, susceptible to a
      variety of diseases, which can lead to losses in yield and fruit quality.
      Although screening studies have identified resistant germplasm for some important
      diseases, still little is known about the molecular basis underlying that
      resistance. The most predominant type of resistance (R) genes contains nucleotide
      binding site and leucine rich repeat (NBS-LRR) domains. The identification and
      characterization of such a gene family in blueberry would enhance the foundation
      of knowledge needed for its genetic improvement. In this study, we searched for
      and found a total of 106 NBS-encoding genes (including 97 NBS-LRR) in the current
      blueberry genome. The NBS genes were grouped into eleven distinct classes based
      on their domain architecture. More than 22% of the NBS genes are present in
      clusters. Ten genes were mapped onto seven linkage groups. Phylogenetic analysis
      grouped these genes into two major clusters based on their structural variation,
      the first cluster having toll and interleukin-1 like receptor (TIR) domains and
      most of the second cluster containing a coiled-coil domain. Our study provides
      new insight into the NBS gene family in blueberry and is an important resource
      for the identification of functional R-genes.

PMID- 29467426
TI  - Neuronal avalanche dynamics indicates different universality classes in neuronal
      cultures.
AB  - Neuronal avalanches have become an ubiquitous tool to describe the activity of
      large neuronal assemblies. The emergence of scale-free statistics with well
      defined exponents has led to the belief that the brain might operate near a
      critical point. Yet not much is known in terms of how the different exponents
      arise or how robust they are. Using calcium imaging recordings of dissociated
      neuronal cultures we show that the exponents are not universal, and that
      significantly different exponents arise with different culture preparations,
      leading to the existence of different universality classes. Naturally developing
      cultures show avalanche statistics consistent with those of a mean-field
      branching process, however, cultures grown in the presence of folic acid
      metabolites appear to be in a distinct universality class with significantly
      different critical exponents. Given the increased synaptic density and number of
      feedback loops in folate reared cultures, our results suggest that network
      topology plays a leading role in shaping the avalanche dynamics. We also show
      that for both types of cultures pronounced correlations exist in the sizes of
      neuronal avalanches indicating size clustering, being much stronger in folate
      reared cultures.

PMID- 29467428
TI  - Dynamic air/liquid pockets for guiding microscale flow.
AB  - Microscale flows of fluids are mainly guided either by solid matrices or by
      liquid-liquid interfaces. However, the solid matrices are plagued with persistent
      fouling problems, while liquid-liquid interfaces are limited to low-pressure
      applications. Here we report a dynamic liquid/solid/gas material containing both
      air and liquid pockets, which are formed by partially infiltrating a porous
      matrix with a functional liquid. Using detailed theoretical and experimental
      data, we show that the distribution of the air- and liquid-filled pores is
      responsive to pressure and enables the formation and instantaneous recovery of
      stable liquid-liquid interfaces that sustain a wide range of pressures and
      prevent channel contamination. This adaptive design is demonstrated for polymeric
      materials and extended to metal-based systems that can achieve unmatched
      mechanical and thermal stability. Our platform with its unique adaptive pressure
      and antifouling capabilities may offer potential solutions to flow control in
      microfluidics, medical devices, microscale synthesis, and biological assays.

PMID- 29467427
TI  - High-efficiency RNA-based reprogramming of human primary fibroblasts.
AB  - Induced pluripotent stem cells (iPSCs) hold great promise for regenerative
      medicine; however, their potential clinical application is hampered by the low
      efficiency of somatic cell reprogramming. Here, we show that the synergistic
      activity of synthetic modified mRNAs encoding reprogramming factors and miRNA
      367/302s delivered as mature miRNA mimics greatly enhances the reprogramming of
      human primary fibroblasts into iPSCs. This synergistic activity is dependent upon
      an optimal RNA transfection regimen and culturing conditions tailored
      specifically to human primary fibroblasts. As a result, we can now generate up to
      4,019 iPSC colonies from only 500 starting human primary neonatal fibroblasts and
      reprogram up to 90.7% of individually plated cells, producing multiple sister
      colonies. This methodology consistently generates clinically relevant,
      integration-free iPSCs from a variety of human patient's fibroblasts under feeder
      free conditions and can be applicable for the clinical translation of iPSCs and
      studying the biology of reprogramming.

PMID- 29467429
TI  - A Genetic Screen for Investigating the Human Lysosomal CystineTransporter,
      Cystinosin.
AB  - Cystinosin, a lysosomal transporter is involved in the efflux of cystine from the
      lysosome to the cytosol. Mutations in the human cystinosin gene (CTNS) cause
      cystinosis, a recessive autosomal disorder. Studies on cystinosin have been
      limited by the absence of a robust genetic screen. In the present study we have
      developed a dual strategy for evaluating cystinosin function that is amenable to
      rapid genetic analysis. We show that human cystinosin expressed in this yeast
      confers growth on cystine when the protein is mistargeted to the plasma membrane
      by the deletion of the C-terminal targeting signal, GYQDL. We also screened a
      vacuolar protein sorting deletion library, and subsequently created multiple vps
      deletion mutants for kinetic studies. The double deletion, vps1Deltavps17Delta,
      greatly enhanced uptake. This enabled validation by kinetic studies, including
      first studies on the WT CTNS protein (that contained the GYQDL motif). Using this
      screen we isolated several gain of function mutants, G131S/D, G309S/D, A137V,
      G197R, S270T, L274F and S312N showing enhanced growth on low concentrations of
      cystine. Kinetic analysis yielded insights into the role of the residues
      (including one of the patient mutations, G197R). The results indicate that the
      screen could be effectively used for interrogating and understanding the CTNS
      protein.

PMID- 29467430
TI  - Evaluation of Macaca radiata as a non-human primate model of Dengue virus
      infection.
AB  - Dengue virus (DENV) causes a wide range of illnesses in humans, including dengue
      fever and dengue haemorrhagic fever. Current animal models of DENV infection are
      limited for understanding infectious diseases in humans. Bonnet monkeys (Macaca
      radiata), a type of Old World monkey, have been used to study experimental and
      natural infections by flaviviruses, but Old World monkeys have not yet been used
      as DENV infection models. In this study, the replication levels of several DENV
      strains were evaluated using peripheral blood mononuclear cells. Our findings
      indicated that DENV-4 09-48 strain, isolated from a traveller returning from
      India in 2009, was a highly replicative virus. Three bonnet monkeys were infected
      with 09-48 strain and antibody responses were assessed. DENV nonstructural
      protein 1 antigen was detected and high viraemia was observed. These results
      indicated that bonnet monkeys and 09-48 strain could be used as a reliable
      primate model for the study of DENV.

PMID- 29467431
TI  - Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal
      ischemia/reperfusion-injury.
AB  - Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury
      (AKI). Non-coding RNAs are crucially involved in its pathophysiology. We
      identified hypoxia-induced long non-coding RNA Malat1 (Metastasis Associated Lung
      Adenocarcinoma Transcript 1) to be upregulated in renal I/R injury. We here
      elucidated the functional role of Malat1 in vitro and its potential contribution
      to kidney injury in vivo. Malat1 was upregulated in kidney biopsies and plasma of
      patients with AKI, in murine hypoxic kidney tissue as well as in cultured and ex
      vivo sorted hypoxic endothelial cells and tubular epithelial cells. Malat1 was
      transcriptionally activated by hypoxia-inducible factor 1-alpha. In vitro, Malat1
      inhibition reduced proliferation and the number of endothelial cells in the S
      phase of the cell cycle. In vivo, Malat1 knockout and wildtype mice showed
      similar degrees of outer medullary tubular epithelial injury, proliferation,
      capillary rarefaction, inflammation and fibrosis, survival and kidney function.
      Small-RNA sequencing and whole genome expression analysis revealed only minor
      changes between ischemic Malat1 knockout and wildtype mice. Contrary to previous
      studies, which suggested a prominent role of Malat1 in the induction of disease,
      we did not confirm an in vivo role of Malat1 concerning renal I/R-injury.

PMID- 29467432
TI  - Printed Receive Coils with High Acoustic Transparency for Magnetic Resonance
      Guided Focused Ultrasound.
AB  - In magnetic resonance guided focused ultrasound (MRgFUS) therapy sound waves are
      focused through the body to selectively ablate difficult to access lesions and
      tissues. A magnetic resonance imaging (MRI) scanner non-invasively tracks the
      temperature increase throughout the tissue to guide the therapy. In clinical MRI,
      tightly fitted hardware comprised of multichannel coil arrays are required to
      capture high quality images at high spatiotemporal resolution. Ablating tissue
      requires a clear path for acoustic energy to travel but current array materials
      scatter and attenuate acoustic energy. As a result coil arrays are placed outside
      of the transducer, clear of the beam path, compromising imaging speed,
      resolution, and temperature accuracy of the scan. Here we show that when coil
      arrays are fabricated by additive manufacturing (i.e., printing), they exhibit
      acoustic transparency as high as 89.5%. This allows the coils to be placed in the
      beam path increasing the image signal to noise ratio (SNR) five-fold in phantoms
      and volunteers. We also characterize printed coil materials properties over time
      when submerged in the water required for acoustic coupling. These arrays offer
      high SNR and acceleration capabilities, which can address current challenges in
      treating head and abdominal tumors allowing MRgFUS to give patients better
      outcomes.

PMID- 29467433
TI  - Trend and risk factors of low birth weight and macrosomia in south China, 2005
      2017: a retrospective observational study.
AB  - The percentages of low birth weight (LBW) increased from 7.7% in 2005 to 11.3% in
      2011 and declined to 8.1% in 2017. For very low birth weight (VLBW) individuals,
      the proportion declined -1.0% annually, from 2.5% in 2005 to 1.4% in 2017. Among
      moderately low birth weight (MLBW) individuals, the proportion first increased
      12.8% annually, from 5.0% in 2005 to 9.3% in 2011, and then declined -3.8%
      annually, from 9.4% in 2011 to 7.0% in 2017. The percentages of macrosomia
      monotone decreased from 4.0% in 2005 to 2.5% in 2017, an annual decline of -4.0%.
      Multiple regression analyses showed that boys, maternal age, hypertensive
      disorders complicating pregnancy (HDCP), and diabetes were significant risk
      factors for LBW. Boys, maternal age, gestational age, HDCP, diabetes, and
      maternal BMI were significant risk factors for macrosomia. Although the relevant
      figures declined slightly in our study, it is likely that LBW and macrosomia will
      remain a major public health issue over the next few years in China. More
      research aimed at control and prevention of these risk factors for LBW and
      macrosomia and their detrimental outcome in the mother and perinatal child should
      be performed in China.

PMID- 29467434
TI  - Conformational IgE Epitope Mapping of Der p 2 and the Evaluations of Two
      Candidate Hypoallergens for Immunotherapy.
AB  - Epitope mapping of Der p 2, a clinically important dust-mite allergen is the
      first step in designing immunotherapy hypoallergen vaccine candidates. Twenty-one
      single alanine mutants of Der p 2 were generated and their secondary structure
      was analysed using circular dichroism spectra. Only one mutant, K96A resulted in
      a misfolded protein. All mutants were tested for serum IgE reactivity using serum
      from dust mite allergic individuals by immuno dot-blots. Mutations to five
      residues, N10, E25, K77, K96 and E102 consistently showed reduced IgE reactions
      compared to wild-type Der p 2, and therefore these residues constitute the major
      IgE epitopes of Der p 2. Two mutants with consistent low IgE binding, K96A and
      E102A, were subsequently evaluated as hypoallergen candidates. IgG antibodies
      raised in mice against both mutants could inhibit human IgE-binding to WT Der p
      2. Both mutants had intact T-cell epitopes as they were able to stimulate
      peripheral blood mononuclear cell proliferation similar to WT Der p 2. However, a
      switch in Th1:Th2 cytokine profile was not observed. In summary, we have
      identified the major conformational epitopes of Der p 2, and evaluated two Der p
      2 hypoallergen vaccine candidates for immunotherapy.

PMID- 29467435
TI  - Visualisation of DCP, a nerve agent mimic, in Catfish brain by a simple
      chemosensor.
AB  - A chemosensor, 3-aminophenol-based rhodamine conjugate (ARC) has been developed
      for visualisation of diethylchlorophosphate (DCP), mimic of a chemical warfare
      agent, in Catfish brain. The simple detection of DCP by "turn-on" fluorescence
      property of the chemosensor makes it unique for easy and rapid in vivo and in
      vitro detection of DCP with the detection limit of 5.6 nM.

PMID- 29467436
TI  - Fabrication of transparent hemispherical 3D nanofibrous scaffolds with radially
      aligned patterns via a novel electrospinning method.
AB  - Tissue engineering has significantly contributed to the development of optimal
      treatments for individual injury sites based on their unique functional and
      histologic properties. Human organs and tissue have three-dimensional (3D)
      morphologies; for example, the morphology of the eye is a spherical shape.
      However, most conventional electrospinning equipment is only capable of
      fabricating a two-dimensional (2D) structured fibrous scaffold and no report is
      available on a 3D electrospinning method to fabricate a hemispherical scaffold to
      mimic the native properties of the cornea, including microscopic to macroscopic
      morphology and transparency. We proposed a novel electrospinning method using a
      single nonconductive hemispherical device and a metal pin. A designed peg-top
      shaped collector, a hemispherical nonconductive device with a metal pin in the
      center and copper wire forming a circle around at the edge was attached to a
      conventional conductive collector. A 3D hemispherical transparent scaffold with
      radially aligned nanofibers was successfully fabricated with the designed peg-top
      collector. In summary, our fabricated 3D electrospun scaffold is expected to be
      suitable for the treatment of injuries of ocular tissues owing to the
      hemispherical shape and radially aligned nanofibers which can guide the direction
      of the main collagen and cellular actin filament in the extracellular matrix.

PMID- 29467437
TI  - Accelerated repetitive transcranial magnetic stimulation in the treatment of
      depression.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is increasingly used
      clinically in the treatment of patients with major depressive disorder (MDD).
      However, rTMS treatment response can be slow. Early research suggests that
      accelerated forms of rTMS may be effective but no research has directly evaluated
      a schedule of accelerated rTMS compared to standard rTMS. To assess the efficacy
      of accelerated rTMS compared to standard daily rTMS., 115 outpatients with MDD
      received either accelerated rTMS (n = 58) (i.e., 63,000 high frequency rTMS
      pulses delivered as 3 treatments per day over 3 days in week 1, 3 treatments over
      2 days in week 2 and 3 treatments on a single day in week 3) or standard rTMS (n
      = 57) (i.e., 63,000 total high frequency rTMS pulses delivered over 5 days per
      week for 4 weeks) following randomization. There were no significant differences
      in remission or response rates (p > 0.05 for all analyses) or reduction in
      depression scores (Time by group interaction (F (5, 489.452) = 1.711, p = 0.130)
      between the accelerated and standard rTMS treatment groups. Accelerated treatment
      was associated with a higher rate of reported treatment discomfort. It is
      feasible to provide accelerated rTMS treatment for outpatients with depression
      and this is likely to produce meaningful antidepressant effects.

PMID- 29467438
TI  - Lifetime of racetrack skyrmions.
AB  - The skyrmion racetrack is a promising concept for future information technology.
      There, binary bits are carried by nanoscale spin swirls-skyrmions-driven along
      magnetic strips. Stability of the skyrmions is a critical issue for realising
      this technology. Here we demonstrate that the racetrack skyrmion lifetime can be
      calculated from first principles as a function of temperature, magnetic field and
      track width. Our method combines harmonic transition state theory extended to
      include Goldstone modes, with an atomistic spin Hamiltonian parametrized from
      density functional theory calculations. We demonstrate that two annihilation
      mechanisms contribute to the skyrmion stability: At low external magnetic field,
      escape through the track boundary prevails, but a crossover field exists, above
      which the collapse in the interior becomes dominant. Considering a Pd/Fe bilayer
      on an Ir(111) substrate as a well-established model system, the calculated
      skyrmion lifetime is found to be consistent with reported experimental
      measurements. Our simulations also show that the Arrhenius pre-exponential factor
      of escape depends only weakly on the external magnetic field, whereas the pre
      exponential factor for collapse is strongly field dependent. Our results open the
      door for predictive simulations, free from empirical parameters, to aid the
      design of skyrmion-based information technology.

PMID- 29467439
TI  - Optimized Bone Regeneration in Calvarial Bone Defect Based on Biodegradation
      Tailoring Dual-shell Biphasic Bioactive Ceramic Microspheres.
AB  - Bioceramic particulates capable of filling bone defects have gained considerable
      interest over the last decade. Herein, dual-shell bioceramic microspheres
      (CaP@CaSi@CaP, CaSi@CaP@CaSi) with adjustable beta-tricalcium phosphate (CaP) and
      beta-calcium silicate (CaSi) distribution were fabricated using a co-concentric
      capillary system enabling bone repair via a tailorable biodegradation process.
      The in vitro results showed the optimal concentration (1/16 of 200 mg/ml) of
      extracts of dual-shell microspheres could promote bone marrow mesenchymal cell
      (BMSC) proliferation and enhance the level of ALP activity and Alizarin Red
      staining. The in vivo bone repair and microsphere biodegradation in calvarial
      bone defects were compared using micro-computed tomography and histological
      evaluations. The results indicated the pure CaP microspheres were minimally
      resorbed at 18 weeks post-operatively and new bone tissue was limited; however,
      the dual-shell microspheres were appreciably biodegraded with time in accordance
      with the priority from CaSi to CaP in specific layers. The CaSi@CaP@CaSi group
      showed a significantly higher ability to promote bone regeneration than the
      CaP@CaSi@CaP group. This study indicates that the biphasic microspheres with
      adjustable composition distribution are promising for tailoring material
      degradation and bone regeneration rate, and such versatile design strategy is
      thought to fabricate various advanced biomaterials with tailorable biological
      performances for bone reconstruction.

PMID- 29467440
TI  - Metabolic profile associated with distinct behavioral coping strategies of 129Sv
      and Bl6 mice in repeated motility test.
AB  - We investigated the metabolic outcome of different coping strategies in
      129S6/SvEvTac (129Sv) and C57BL/6Ntac (Bl6) strains. Two different batches of
      male 129Sv and Bl6 mice were used. One batch was not subjected to any behavioral
      manipulations (home cage control; HCC), whereas the other batch was treated with
      saline for 11 days and exposed after every treatment to the motor activity
      measurement (repeated motility tested; RMT). Bl6 RMT mice displayed a robust
      increase in number of rearings during repeated testing. 129Sv RMT mice
      experienced significant loss of body weight, but showed enhanced weight gain in
      HCC batch compared to Bl6. Serum metabolites (acylcarnitines, amino acids,
      biogenic amines, hexoses, glycerophospholipids and sphingolipids) were determined
      with AbsoluteIDQ p180 kit. Results of the metabolomic study revealed prominent
      peculiarities between strains in two different conditions. Comparison of both
      batches of mice demonstrated that in Bl6 biogenic amines (acetyl-ornithine, alpha
      amionadipic acid, carnosine) and lysophosphatidylcholine PC(16:1/0:0) dominated.
      However in 129Sv acylcarnitine C5 clearly dominated, indicating shift towards
      short-chain acylcarnitines. Stable strain-specific ratios also emerged for both
      lines, ratio of glycine/PC ae C38:2 for Bl6 and ratios of C5/C0 as well as
      PC(16:0/0:0)/PC(16:1/0:0) for 129Sv. The described metabolic changes probably
      reflect different behavioral coping strategies of 129Sv and Bl6 mice.

PMID- 29467441
TI  - LINC01016 promotes the malignant phenotype of endometrial cancer cells by
      regulating the miR-302a-3p/miR-3130-3p/NFYA/SATB1 axis.
AB  - Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis and cancer
      progression and are tightly associated with the phenotypes of numerous cancers.
      However, the functional roles underlying these effects are unknown. The
      expression levels of LINC01016, miR-302a-3p, miR-3130-3p, NFYA, and SATB1 were
      evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in 33
      endometrial cancer tissues and 20 normal tissues. Bioinformatics analyses,
      luciferase reporter analyses, chromatin immunoprecipitation (ChIP) assays, and
      qRT-PCR assays were performed to verify potential binding sites. The qRT-PCR and
      western blot were used to identify the regulatory mechanisms of LINC01016 in cell
      biological behavior, which were also examined by cell counting kit -8 (CCK-8), 5
      ethynyl-2'-deoxyuridine (EdU) assays, flow cytometry, wound healing assays, and
      transwell assays. LINC01016 was substantially upregulated in endometrial cancer
      tissues, and LINC01016 silencing abolished the malignant behavior of endometrial
      cancer cells. LINC01016 positively rescued the downstream gene nuclear factor YA
      (NFYA) by competitively "sponging" miR-302a-3p and miR-3130-3p. In turn, these
      two miRNAs could inhibit LINC01016 transcription, thus forming two reciprocal
      repression cycles, which influenced the biological behavior of endometrial cancer
      cells. MiR-302a-3p and miR-3130-3p could specifically bind with the 3'-UTR
      regions of NFYA, and NFYA could upregulate the expression of special AT-rich
      sequence-binding protein 1 (SATB1) as a transcriptional factor. This study was
      the first to show that the LINC01016-miR-302a-3p/miR-3130-3p/NFYA/SATB1 axis
      played a crucial role in the occurrence of endometrial cancer. These findings may
      provide relevant insights into the diagnosis and therapy of endometrial cancer.

PMID- 29467442
TI  - The influence of riverine barriers, climate, and topography on the biogeographic
      regionalization of Amazonian anurans.
AB  - We evaluated five non-mutually exclusive hypotheses driving the biogeographic
      regions of anuran species in the Amazonia. We overlaid extent-of-occurrence maps
      for anurans 50 * 50 km cells to generate a presence-absence matrix. This matrix
      was subjected to a cluster analysis to identify the pattern and number of
      biogeographic regions for the dataset. Then, we used multinomial logistic
      regression models and deviance partitioning to explore the relative importance of
      contemporary and historical climate variables, topographic complexity, riverine
      barriers and vegetation structure in explaining the biogeographic regions
      identified. We found seven biogeographic regions for anurans in the Amazonia. The
      major rivers in the Amazonia made the largest contribution to explaining the
      variability in anuran biogeographic regions, followed by climate variables and
      topography. The barrier effect seems to be strong for some rivers, such as the
      Amazon and Madeira, but other Amazonia rivers appear to not be effective
      barriers. Furthermore, climate and topographical variables provide an
      environmental gradient driving the species richness and anuran range-size
      distributions. Therefore, our results provide a spatially explicit framework that
      could be used to address conservation and management issues of anuran diversity
      for the largest tropical forests in the world.

PMID- 29467443
TI  - Emerging views of the nucleus as a cellular mechanosensor.
AB  - The ability of cells to respond to mechanical forces is critical for numerous
      biological processes. Emerging evidence indicates that external mechanical forces
      trigger changes in nuclear envelope structure and composition, chromatin
      organization and gene expression. However, it remains unclear if these processes
      originate in the nucleus or are downstream of cytoplasmic signals. Here we
      discuss recent findings that support a direct role of the nucleus in cellular
      mechanosensing and highlight novel tools to study nuclear mechanotransduction.

PMID- 29467444
TI  - Evaluation of digital real-time PCR assay as a molecular diagnostic tool for
      single-cell analysis.
AB  - In a single-cell study, isolating and identifying single cells are essential, but
      these processes often require a large investment of time or money. The aim of
      this study was to isolate and analyse single cells using a novel platform, the
      PanelChipTM Analysis System, which includes 2500 microwells chip and a digital
      real-time polymerase chain reaction (dqPCR) assay, in comparison with a standard
      PCR (qPCR) assay. Through the serial dilution of a known concentration standard,
      namely pUC19, the accuracy and sensitivity levels of two methodologies were
      compared. The two systems were tested on the basis of expression levels of the
      genetic markers vimentin, E-cadherin, N-cadherin and GAPDH in A549 lung carcinoma
      cells at two known concentrations. Furthermore, the influence of a known PCR
      inhibitor commonly found in blood samples, heparin, was evaluated in both
      methodologies. Finally, mathematical models were proposed and separation method
      of single cells was verified; moreover, gene expression levels during epithelial
      mesenchymal transition in single cells under TGFbeta1 treatment were measured.
      The drawn conclusion is that dqPCR performed using PanelChipTM is superior to the
      standard qPCR in terms of sensitivity, precision, and heparin tolerance. The
      dqPCR assay is a potential tool for clinical diagnosis and single-cell
      applications.

PMID- 29467445
TI  - Vaccine-induced antigen-specific regulatory T cells attenuate the antiviral
      immunity against acute influenza virus infection.
AB  - Peptide-based T cell vaccines targeting the conserved epitopes of influenza virus
      can provide cross-protection against distantly related strains, but they are
      generally not immunogenic. Foreign antigen-specific regulatory T (Treg) cells are
      induced under subimmunogenic conditions peripherally, although their development
      and role in vaccine-mediated antiviral immunity is unclear. Here, we demonstrated
      primary vaccination with peptides alone significantly induced antigen-specific
      Foxp3+ Treg cells, which were further expanded by repeated vaccination with
      unadjuvanted peptides. Certain adjuvants, including CpG, suppressed the induction
      and expansion of antigen-specific Treg cells by peptide vaccination.
      Interestingly, secondary influenza virus infection significantly increased the
      frequency of preexisting antigen-specific Treg cells, although primary infection
      barely induced them. Importantly, specific depletion of vaccine-induced antigen
      specific Treg cells promoted influenza viral clearance, indicating their
      inhibitory role in vivo. Immunization with CpG-adjuvanted peptides by the
      subcutaneous prime-intranasal-boost strategy restricted the recruitment and
      accumulation of antigen-specific Treg cells in lung, and stimulated robust T cell
      immunity. Finally, subcutaneous prime-intranasal-boost immunization with CpG
      adjuvanted peptides or whole-inactivated influenza vaccines protected mice from
      heterosubtypic influenza virus infection. In conclusion, antigen-specific Treg
      cells induced by peptide vaccines attenuate the antiviral immunity against
      influenza virus infection. CpG-adjuvanted peptide vaccines provide heterosubtypic
      influenza protection probably by inhibiting Treg development and enhancing T cell
      immunity.

PMID- 29467446
TI  - Oral cholera vaccination promotes homing of IgA+ memory B cells to the large
      intestine and the respiratory tract.
AB  - Oral cholera vaccination is used to induce immune responses in the intestines to
      protect against cholera infection. However, oral vaccination may also affect
      immune responses in other mucosal tissues. To study this, tissue-specific homing
      potential and kinetics of B-cell responses were characterized after oral cholera
      vaccination. Healthy adult volunteers received two doses of Dukoral(r) and blood,
      saliva, nasal wash, and fecal samples were collected over time to detect vaccine
      specific antibodies. Additionally, homing potential of lymphocytes to small
      intestine, colon, airways, skin, and periphery was measured by expression of
      Integrin beta1 and beta7, CCR9, CCR10, CCR7, and CLA. After vaccination, antibody
      responses to cholera toxin B (CTB) and Dukoral(r) were detected in serum and
      nasal wash. CTB-specific memory B cells in peripheral blood and tissue homing
      profiles of memory B cells peaked at day 18. IgA+ memory B cells expressed
      markers that enable homing to the airways and colon, while IgA- memory B cells
      primarily expressed small-intestine-homing markers. These data show that oral
      cholera vaccination has a differential effect on immune responses in various
      mucosal sites, including the respiratory tract.

PMID- 29467447
TI  - Notch signaling represents an important checkpoint between follicular T-helper
      and canonical T-helper 2 cell fate.
AB  - Type-2 immunity is regulated by two distinct CD4+ T-cell subsets. T follicular
      helper (Tfh) cells are required for humoral hallmarks of type-2 inflammation. T
      helper type-2 (Th2) cells orchestrate type-2 inflammation in peripheral tissues,
      such as the lung and intestine. Given the importance of Notch signaling in the
      establishment of other CD4+ T-helper cell subsets, we investigated whether
      canonical Notch activation could differentially impact Tfh and Th2 cell fate
      during the induction of type-2 immunity. These studies show that Tfh cell, but
      not Th2 cell, generation and function is reliant on Notch signaling. While early
      Tfh cell specification is influenced by functional Notch ligands on classical
      dendritic cells, functional Notch ligands on cells other than dendritic cells, T
      cells, B cells, and follicular dendritic cells are sufficient to achieve full Tfh
      cell commitment. These findings identify Notch signaling as an early lineage
      determining factor between Tfh and Th2 cell fate.

PMID- 29467449
TI  - Systemic lupus erythematosus: Antihypertensive drug has dual effects.

PMID- 29467448
TI  - Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell
      killing of Cryptococcus and Candida.
AB  - Natural killer (NK) cells use the activating receptor NKp30 as a microbial
      pattern-recognition receptor to recognize, activate cytolytic pathways, and
      directly kill the fungi Cryptococcus neoformans and Candida albicans. However,
      the fungal pathogen-associated molecular pattern (PAMP) that triggers NKp30
      mediated killing remains to be identified. Here we show that beta-1,3-glucan, a
      component of the fungal cell wall, binds to NKp30. We further demonstrate that
      beta-1,3-glucan stimulates granule convergence and polarization, as shown by live
      cell imaging. Through Src Family Kinase signaling, beta-1,3-glucan increases
      expression and clustering of NKp30 at the microbial and NK cell synapse to induce
      perforin release for fungal cytotoxicity. Rather than blocking the interaction
      between fungi and NK cells, soluble beta-1,3-glucan enhances fungal killing and
      restores defective cryptococcal killing by NK cells from HIV-positive
      individuals, implicating beta-1,3-glucan to be both an activating ligand and a
      soluble PAMP that shapes NK cell host immunity.

PMID- 29467450
TI  - Vasculitis syndromes: A closer look at skin involvement in vasculitis.

PMID- 29467451
TI  - Bone: Direct contact between mature osteoblasts and osteoclasts.

PMID- 29467452
TI  - Bone: ER stress causes osteoclastogenesis.

PMID- 29467453
TI  - Osteoarthritis: Bisphosphonates and OA - is there a bone and joint connection?

PMID- 29467454
TI  - Autoimmunity: TLR7 evades silencing in human immune cells.

PMID- 29467456
TI  - Genome-wide CRISPR screen reveals SGOL1 as a druggable target of sorafenib
      treated hepatocellular carcinoma.
AB  - The genome-wide clustered regularly interspaced short palindromic repeats
      (CRISPR) screen is a powerful tool used to identify therapeutic targets that can
      be harnessed for cancer treatment. This study aimed to assess the efficacy of
      genome-wide CRISPR screening to identify druggable genes associated with
      sorafenib-treated hepatocellular carcinoma (HCC). A genome-scale CRISPR knockout
      (GeCKO v2) library containing 123,411 single guide RNAs (sgRNAs) was used to
      identify loss-of-function mutations conferring sorafenib resistance upon HCC
      cells. Resistance gene screens identified SGOL1 as an indicator of prognosis of
      patients treated with sorafenib. Of the 19,050 genes tested, the knockout screen
      identified inhibition of SGOL1 expression as the most-effective genetic
      suppressor of sorafenib activity. Analysis of the survival of 210 patients with
      HCC after hepatic resection revealed that high SGOL1 expression shortened overall
      survival (P = 0.021). Further, matched pairs analysis of the TCGA database
      revealed that SGOL1 is differentially expressed. When we used a lentivirus Cas9
      vector to determine the effect of targeting SGOL1 with a specific sgRNA in HCC
      cells, we found that SGOL1 expression was efficiently inhibited and that loss of
      SGOL1 was associated with sorafenib resistance. Further, loss of SGOL1 from HCC
      cell decreased the cytotoxicity of sorafenib in vivo. We conclude that the CRISPR
      screen is a powerful tool for therapeutic target analysis of sorafenib treatment
      and that SGOL1 serves as a druggable target for HCC treated with sorafenib and an
      indicator of prognosis.

PMID- 29467455
TI  - Lack of cystic fibrosis transmembrane conductance regulator disrupts fetal airway
      development in pigs.
AB  - Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function
      causes cystic fibrosis (CF), predisposing the lungs to chronic infection and
      inflammation. In young infants with CF, structural airway defects are
      increasingly recognized before the onset of significant lung disease, which
      suggests a developmental origin and a possible role in lung disease pathogenesis.
      The role(s) of CFTR in lung development is unclear and developmental studies in
      humans with CF are not feasible. Young CF pigs have structural airway changes and
      develop spontaneous postnatal lung disease similar to humans; therefore, we
      studied lung development in the pig model (non-CF and CF). CF trachea and
      proximal airways had structural lesions detectable as early as pseudoglandular
      development. At this early developmental stage, budding CF airways had smaller,
      hypo-distended lumens compared to non-CF airways. Non-CF lung explants exhibited
      airway lumen distension in response to forskolin/IBMX as well as to fibroblast
      growth factor (FGF)-10, consistent with CFTR-dependent anion transport/secretion,
      but this was lacking in CF airways. We studied primary pig airway epithelial cell
      cultures and found that FGF10 increased cellular proliferation (non-CF and CF)
      and CFTR expression/function (in non-CF only). In pseudoglandular stage lung
      tissue, CFTR protein was exclusively localized to the leading edges of budding
      airways in non-CF (but not CF) lungs. This discreet microanatomic localization of
      CFTR is consistent with the site, during branching morphogenesis, where airway
      epithelia are responsive to FGF10 regulation. In summary, our results suggest
      that the CF proximal airway defects originate during branching morphogenesis and
      that the lack of CFTR-dependent anion transport/liquid secretion likely
      contributes to these hypo-distended airways.

PMID- 29467457
TI  - Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by
      increasing killer cell lectin-like receptor C3 expression by fumarate.
AB  - Adenylosuccinate lyase (ADSL) is an enzyme that plays important roles in de novo
      purine synthesis. Although ADSL was reported to be upregulated in various
      malignancies, such as colorectal, breast, and prostate cancer, as well as
      gliomas, the mechanism by which elevated ADSL expression contributes to cancer
      has not been elucidated. We previously performed a shotgun proteomics analysis to
      characterize specific proteins associated with the properties of the aldehyde
      dehydrogenase (ALDH)-high cell population, which was reported to be involved in
      tumorigenic potential, and showed that ADSL expression is upregulated in the ALDH
      high population of endometrial cancer. Here, we showed that ADSL is involved in
      endometrial cancer aggressiveness by regulating expression of killer cell lectin
      like receptor C3 (KLRC3), which is a receptor expressed on natural killer cells.
      Immunohistochemical analysis indicated that ADSL expression increased as
      endometrioid carcinoma specimens became more poorly differentiated and higher
      degree of primary tumor progression. Knockdown of ADSL in endometrial cancer
      cells decreased cell proliferation, migration, and invasive capability, and
      caused the cells to adopt a more rounded shape. DNA microarray analysis and
      quantitative real-time PCR showed that KLRC3 expression was decreased in ADSL
      knockdown cells. Knockdown of KLRC3 in endometrial cancer cells resulted in the
      same phenotype as knockdown of ADSL. Moreover, fumarate, which could be produced
      by ADSL and was recently shown to be an oncometabolite, recovered KLRC3
      expression in ADSL knockdown cells, suggesting that fumarate produced by ADSL
      could regulate KLRC3 expression. Our findings indicate that ADSL enhances cell
      proliferation, migration, and invasive capability through regulation of KLRC3
      expression by fumarate.

PMID- 29467458
TI  - Maresin 1 attenuates mitochondrial dysfunction through the ALX/cAMP/ROS pathway
      in the cecal ligation and puncture mouse model and sepsis patients.
AB  - Inflammation always accompanies infection during sepsis. Mitochondrial
      dysfunction and the role of reactive oxygen species (ROS) produced by
      mitochondria have been proposed in the pathogenesis of sepsis. Maresins have
      protective and resolving effects in experimental models of infection. In the
      present study, we investigated the effects of maresin 1 (MaR1) on mitochondrial
      function in cecal ligation and puncture (CLP)-induced sepsis and sepsis patients
      to identify mechanisms underlying maresin 1-mediated stimulation of ROS in
      mitochondria. We found that treatment with MaR1 significantly inhibited
      production of cytokines, decreased bacterial load in the peritoneal lavage fluid,
      reduced the number of neutrophils, decreased lactic acid level and upregulated
      cyclic AMP (cAMP) concentration, with the outcome of decreased lung injury in CLP
      induced sepsis in mice. The effects of MaR1 on downregulation nitric oxide (NOX)
      activity, improvement CAT and SOD activity to inhibit ROS production in
      mitochondria was dependent on lipoxin receptor (ALX) and cAMP. Survival rates
      were significantly increased after the treatment of mice with MaR1. In BMDM
      stimulated with LPS, MaR1 inhibited the ROS production, downregulated enzyme
      activity, reduced mtO2 production, increased mitochondrial membrane potential,
      improved adenosine triphosphate (ATP) content and mitochondrial DNA (mtDNA) copy
      number. Finally, the effects of MaR1 on ROS production in the blood of healthy
      volunteers stimulated with LPS or sepsis patients were associated with ALX and
      cAMP. Taken together, these data suggest that treatment with MaR1 could attenuate
      mitochondrial dysfunction during sepsis through regulating ROS production.

PMID- 29467459
TI  - Gate Modulation of the Spin-orbit Interaction in Bilayer Graphene Encapsulated by
      WS2 films.
AB  - Graphene has gigantic potential in the development of advanced spintronic
      devices. The interfacial interactions of graphene with semiconducting transition
      metal dichalcogenides improve the electronic properties drastically, making it an
      intriguing candidate for spintronic applications. Here, we fabricated bilayer
      graphene encapsulated by WS2 layers to exploit the interface-induced spin-orbit
      interaction (SOI). We designed a dual gated device, where the SOI is tuned by
      gate voltages. The strength of induced SOI in the bilayer graphene is
      dramatically elevated, which leads to a strong weak antilocalization (WAL) effect
      at low temperature. The quantitative analysis of WAL demonstrates that the spin
      relaxation time is 10 times smaller than in bilayer graphene on conventional
      substrates. To support these results, we also examined Shubnikov-de Haas (SdH)
      oscillations, which give unambiguous evidence of the zero-field spin-splitting in
      our bilayer graphene. The spin-orbit coupling constants estimated by two
      different measurements (i.e., the WAL effect and SdH oscillations) show close
      values as a function of gate voltage, supporting the self-consistency of this
      study's experimental results. The gate modulation of the SOI in bilayer graphene
      encapsulated by WS2 films establishes a novel way to explore the manipulation of
      spin-dependent transport through an electric field.

PMID- 29467460
TI  - Early antiretroviral therapy on reducing HIV transmission in China: strengths,
      weaknesses and next focus of the program.
AB  - Early antiretroviral therapy (ART) initiation is a recommended public health
      approach for the prevention of HIV-1 transmission. In this cohort study, we
      included 13132 serodiscordant couples. ART was initiated for patients with CD4+ T
      cell counts less than 200 cells/uL, 350 cells/uL, and 500 cells/uL respectively.
      This divided the ART treated couples into three groups. Univariate and
      multivariate intention-to-treat analyses were performed to examine the
      association between the study groups. Early-ART initiation was associated with a
      45% lower risk of partner infection than was late-ART initiation (AHR 0.55, 95%
      CI, 0.37-0.81). Mid-ART initiation was associated with a 39% lower risk of
      partner infection than was late-ART initiation (AHR 0.61, 95% CI, 0.48-0.78).
      However, the risk reduction between the early and mid-ART groups was not
      significant. Drug compliance (AHR 1.55, 95% CI 1.03-2.35) and increased baseline
      viral load (AHR 1.41, 95% CI 1.33-1.51) were associated with an increased risk of
      infections among partners in the treatment. Prevention of HIV transmission as a
      result of early ART initiation was feasible on national and regional scales;
      however, many factors, such as the motivation to commence ART, adherence, and
      attrition, may affect the impact of this strategy in programmatic settings.

PMID- 29467461
TI  - The association of aspirin use with severity of acute exacerbation of chronic
      obstructive pulmonary disease: a retrospective cohort study.
AB  - Little is known about the effect of long-term aspirin use on acute severity of
      COPD. We hypothesized that, in patients hospitalized for acute exacerbation of
      COPD (AECOPD), long-term aspirin use is associated with lower risks of disease
      severity (in-hospital death, mechanical ventilation use, and hospital length-of
      stay). We conducted a retrospective cohort study using large population-based
      data from 2012 through 2013. Among 206,686 patients (aged >=40 years)
      hospitalized for AECOPD, aspirin users had lower in-hospital mortality (1.0 vs.
      1.4%; OR 0.60 [95% CI 0.50-0.72]; P < 0.001) and lower risk of invasive
      mechanical ventilation use (1.7 vs. 2.6%; OR 0.64 [95% CI 0.55-0.73]; P < 0.001)
      compared to non-users, while there was no significant difference in risks of non
      invasive positive pressure ventilation use. Length-of-stay was shorter in aspirin
      users compared to non-users (P < 0.001). In sum, in patients with AECOPD, aspirin
      use was associated with lower rates of in-hospital mortality and invasive
      mechanical ventilation use, and shorter length-of-stay.

PMID- 29467462
TI  - hiPSC-derived neural stem cells from patients with schizophrenia induce an
      impaired angiogenesis.
AB  - Schizophrenia is a neurodevelopmental disease characterized by cerebral
      connectivity impairment and loss of gray matter. It was described in adult
      schizophrenia patients (SZP) that concentration of VEGFA, a master angiogenic
      factor, is decreased. Recent evidence suggests cerebral hypoperfusion related to
      a dysfunctional Blood Brain Barrier (BBB) in SZP. Since neurogenesis and blood
      vessel formation occur in a coincident and coordinated fashion, a defect in
      neurovascular development could result in increased vascular permeability and,
      therefore, in poor functionality of the SZP's neurons. Here, we characterized the
      conditioned media (CM) of human induced Pluripotent Stem Cells (hiPSC)-derived
      Neural Stem Cells of SZP (SZP NSC) versus healthy subjects (Ctrl NSC), and its
      impact on angiogenesis. Our results reveal that SZP NSC have an imbalance in the
      secretion and expression of several angiogenic factors, among them non-canonical
      neuro-angiogenic guidance factors. SZP NSC migrated less and their CM was less
      effective in inducing migration and angiogenesis both in vitro and in vivo. Since
      SZP originates during embryonic brain development, our findings suggest a
      defective crosstalk between NSC and endothelial cells (EC) during the formation
      of the neuro-angiogenic niche.

PMID- 29467464
TI  - Loss of the Drosophila m-AAA mitochondrial protease paraplegin results in
      mitochondrial dysfunction, shortened lifespan, and neuronal and muscular
      degeneration.
AB  - The progressive accumulation of dysfunctional mitochondria is implicated in aging
      and in common diseases of the elderly. To oppose this occurrence, organisms
      employ a variety of strategies, including the selective degradation of
      oxidatively damaged and misfolded mitochondrial proteins. Genetic studies in
      yeast indicate that the ATPase Associated with diverse cellular Activities (AAA+)
      family of mitochondrial proteases account for a substantial fraction of this
      protein degradation, but their metazoan counterparts have been little studied,
      despite the fact that mutations in the genes encoding these proteases cause a
      variety of human diseases. To begin to explore the biological roles of the
      metazoan mitochondrial AAA+ protease family, we have created a CRISPR/Cas9 allele
      of the Drosophila homolog of SPG7, which encodes an inner membrane-localized AAA+
      protease known as paraplegin. Drosophila SPG7 mutants exhibited shortened
      lifespan, progressive locomotor defects, sensitivity to chemical and
      environmental stress, and muscular and neuronal degeneration. Ultrastructural
      examination of photoreceptor neurons indicated that the neurodegenerative
      phenotype of SPG7 mutants initiates at the synaptic terminal. A variety of
      mitochondrial defects accompanied the degenerative phenotypes of SPG7 mutants,
      including altered axonal transport of mitochondria, accumulation of electron
      dense material in the matrix of flight muscle mitochondria, reduced activities of
      respiratory chain complexes I and II, and severely swollen and dysmorphic
      mitochondria in the synaptic terminals of photoreceptors. Drosophila SPG7 mutants
      recapitulate key features of human diseases caused by mutations in SPG7, and thus
      provide a foundation for the identification of Drosophila paraplegin substrates
      and strategies that could be used to ameliorate the symptoms of these diseases.

PMID- 29467463
TI  - Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously
      disable TGFbeta enhance the efficacy of cancer immunotherapy.
AB  - A majority of cancers fail to respond to immunotherapy with antibodies targeting
      immune checkpoints, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) or
      programmed death-1 (PD-1)/PD-1 ligand (PD-L1). Cancers frequently express
      transforming growth factor-beta (TGFbeta), which drives immune dysfunction in the
      tumor microenvironment by inducing regulatory T cells (Tregs) and inhibiting CD8+
      and TH1 cells. To address this therapeutic challenge, we invent bifunctional
      antibody-ligand traps (Y-traps) comprising an antibody targeting CTLA-4 or PD-L1
      fused to a TGFbeta receptor II ectodomain sequence that simultaneously disables
      autocrine/paracrine TGFbeta in the target cell microenvironment (a-CTLA4
      TGFbetaRIIecd and a-PDL1-TGFbetaRIIecd). a-CTLA4-TGFbetaRIIecd is more effective
      in reducing tumor-infiltrating Tregs and inhibiting tumor progression compared
      with CTLA-4 antibody (Ipilimumab). Likewise, a-PDL1-TGFbetaRIIecd exhibits
      superior antitumor efficacy compared with PD-L1 antibodies (Atezolizumab or
      Avelumab). Our data demonstrate that Y-traps counteract TGFbeta-mediated
      differentiation of Tregs and immune tolerance, thereby providing a potentially
      more effective immunotherapeutic strategy against cancers that are resistant to
      current immune checkpoint inhibitors.

PMID- 29467465
TI  - Development and validation of a clinical prediction model for patient-reported
      pain and function after primary total knee replacement surgery.
AB  - To develop and validate a clinical prediction model of patient-reported pain and
      function after undergoing total knee replacement (TKR). We used data of 1,649
      patients from the Knee Arthroplasty Trial who received primary TKR across 34
      centres in the UK. The external validation included 595 patients from Southampton
      University Hospital, and Nuffield Orthopaedic Centre (Oxford). The outcome was
      the Oxford Knee Score (OKS) 12-month after TKR. Pre-operative predictors
      including patient characteristics and clinical factors were considered. Bootstrap
      backward linear regression analysis was used. Low pre-operative OKS, living in
      poor areas, high body mass index, and patient-reported anxiety or depression were
      associated with worse outcome. The clinical factors associated with worse outcome
      were worse pre-operative physical status, presence of other conditions affecting
      mobility and previous knee arthroscopy. Presence of fixed flexion deformity and
      an absent or damaged pre-operative anterior cruciate ligament (compared with
      intact) were associated with better outcome. Discrimination and calibration
      statistics were satisfactory. External validation predicted 21.1% of the variance
      of outcome. This is the first clinical prediction model for predicting self
      reported pain and function 12 months after TKR to be externally validated. It
      will help to inform to patients regarding expectations of the outcome after knee
      replacement surgery.

PMID- 29467467
TI  - Synaptic transmission: A hare as well as a tortoise.

PMID- 29467466
TI  - Distinguishing Human Peripheral Blood NK Cells from CD56dimCD16dimCD69+CD103+
      Resident Nasal Mucosal Lavage Fluid Cells.
AB  - Natural killer (NK) cells are members of the innate lymphoid cells group 1
      (ILC1s), which play a critical role in innate host defense against viruses and
      malignancies. While many studies have examined the role of circulating peripheral
      blood (PB) CD56+ NK cells, little is known about the resident CD56+ cell
      population. Therefore, matched CD56+ cells from nasal lavage fluid (NLF) and PB
      of smokers and non-smokers were compared phenotypically, via flow cytometry, and
      functionally, via NK-cell specific gene expression. NLF and PB CD56+ cells had
      similar expression of CD56, but differentially expressed tissue residency (CD69
      and CD103) and cytotoxicity (CD16) markers. In addition, NLF CD56dim cells
      expressed lower levels of cytotoxicity-associated genes, perforin (PRF1) and
      granzyme B (GZMB), and increased levels of cytokines and cell signaling
      molecules, TRAIL, IFNGR2, and IL8, as compared to PB CD56dim cells. In smokers,
      ITGA2 was downregulated in NLF CD56dim cells, while markers of cytotoxic function
      were primarily downregulated in PB CD56dim NK cells. Overall, NLF CD56dim cells
      are a unique cell population that likely play a role in orchestrating innate
      immune responses in the nasal cavity, which is distinct from their role as a non
      antigen-restricted cytotoxic CD56dim lymphocytes in the PB.

PMID- 29467468
TI  - Signalling from the periphery to the brain that regulates energy homeostasis.
AB  - The CNS regulates body weight; however, we still lack a clear understanding of
      what drives decisions about when, how much and what to eat. A vast array of
      peripheral signals provides information to the CNS regarding fluctuations in
      energy status. The CNS then integrates this information to influence acute
      feeding behaviour and long-term energy homeostasis. Previous paradigms have
      delegated the control of long-term energy homeostasis to the hypothalamus and
      short-term changes in feeding behaviour to the hindbrain. However, recent studies
      have identified target hindbrain neurocircuitry that integrates the orchestration
      of individual bouts of ingestion with the long-term regulation of energy balance.

PMID- 29467470
TI  - Emotion: 'Anxiety cells' drive avoidance.

PMID- 29467469
TI  - Effects of adolescent alcohol consumption on the brain and behaviour.
AB  - Per occasion, alcohol consumption is higher in adolescents than in adults in both
      humans and laboratory animals, with changes in the adolescent brain probably
      contributing to this elevated drinking. This Review examines the contributors to
      and consequences of the use of alcohol in adolescents. Human adolescents with a
      history of alcohol use differ neurally and cognitively from other adolescents;
      some of these differences predate the commencement of alcohol consumption and
      serve as potential risk factors for later alcohol use, whereas others emerge from
      its use. The consequences of alcohol use in human adolescents include alterations
      in attention, verbal learning, visuospatial processing and memory, along with
      altered development of grey and white matter volumes and disrupted white matter
      integrity. The functional consequences of adolescent alcohol use emerging from
      studies of rodent models of adolescence include decreased cognitive flexibility,
      behavioural inefficiencies and elevations in anxiety, disinhibition, impulsivity
      and risk-taking. Rodent studies have also showed that adolescent alcohol use can
      impair neurogenesis, induce neuroinflammation and epigenetic alterations, and
      lead to the persistence of adolescent-like neurobehavioural phenotypes into
      adulthood. Although only a limited number of studies have examined comparable
      measures in humans and laboratory animals, the available data provide evidence
      for notable across-species similarities in the neural consequences of adolescent
      alcohol exposure, providing support for further translational efforts in this
      context.

PMID- 29467471
TI  - Network analysis of coronary artery disease risk genes elucidates disease
      mechanisms and druggable targets.
AB  - Genome-wide association studies (GWAS) have identified over two hundred
      chromosomal loci that modulate risk of coronary artery disease (CAD). The genes
      affected by variants at these loci are largely unknown and an untapped resource
      to improve our understanding of CAD pathophysiology and identify potential
      therapeutic targets. Here, we prioritized 68 genes as the most likely causal
      genes at genome-wide significant loci identified by GWAS of CAD and examined
      their regulatory roles in 286 metabolic and vascular tissue gene-protein sub
      networks ("modules"). The modules and genes within were scored for CAD
      druggability potential. The scoring enriched for targets of cardiometabolic drugs
      currently in clinical use and in-depth analysis of the top-scoring modules
      validated established and revealed novel target tissues, biological processes,
      and druggable targets. This study provides an unprecedented resource of tissue
      defined gene-protein interactions directly affected by genetic variance in CAD
      risk loci.

PMID- 29467472
TI  - Effector CD4+ T cells recognize intravascular antigen presented by patrolling
      monocytes.
AB  - Although effector CD4+ T cells readily respond to antigen outside the
      vasculature, how they respond to intravascular antigens is unknown. Here we show
      the process of intravascular antigen recognition using intravital multiphoton
      microscopy of glomeruli. CD4+ T cells undergo intravascular migration within
      uninflamed glomeruli. Similarly, while MHCII is not expressed by intrinsic
      glomerular cells, intravascular MHCII-expressing immune cells patrol glomerular
      capillaries, interacting with CD4+ T cells. Following intravascular deposition of
      antigen in glomeruli, effector CD4+ T-cell responses, including NFAT1 nuclear
      translocation and decreased migration, are consistent with antigen recognition.
      Of the MHCII+ immune cells adherent in glomerular capillaries, only monocytes are
      retained for prolonged durations. These cells can also induce T-cell
      proliferation in vitro. Moreover, monocyte depletion reduces CD4+ T-cell
      dependent glomerular inflammation. These findings indicate that MHCII+ monocytes
      patrolling the glomerular microvasculature can present intravascular antigen to
      CD4+ T cells within glomerular capillaries, leading to antigen-dependent
      inflammation.

PMID- 29467473
TI  - Embryonic lethality in mice lacking Trim59 due to impaired gastrulation
      development.
AB  - TRIM family members have been implicated in a variety of biological processes
      such as differentiation and development. We here found that Trim59 plays a
      critical role in early embryo development from blastocyst stage to gastrula.
      There existed delayed development and empty yolk sacs from embryonic day (E) 8.5
      in Trim59-/- embryos. No viable Trim59-/- embryos were observed beyond E9.5.
      Trim59 deficiency affected primary germ layer formation at the beginning of
      gastrulation. At E6.5 and E7.5, the expression of primary germ layer formation
      associated genes including Brachyury, lefty2, Cer1, Otx2, Wnt3, and BMP4 was
      reduced in Trim59-/- embryos. Homozygous mutant embryonic epiblasts were
      contracted and the mesoderm was absent. Trim59 could interact with actin- and
      myosin-associated proteins. Its deficiency disturbed F-actin polymerization
      during inner cell mass differentiation. Trim59-mediated polymerization of F-actin
      was via WASH K63-linked ubiquitination. Thus, Trim59 may be a critical regulator
      for early embryo development from blastocyst stage to gastrula through modulating
      F-actin assembly.

PMID- 29467475
TI  - Publisher Correction: Evolutionary adaptations to new environments generally
      reverse plastic phenotypic changes.
AB  - The originally published HTML version of this Article contained errors in the
      three equations in the Methods sub-section 'Metabolic network analysis', whereby
      the Greek letter eta (eta) was inadvertently used in place of beta (beta) during
      the production process. These errors have now been corrected in the HTML version
      of the Article; the PDF was correct at the time of publication.

PMID- 29467474
TI  - An in vitro proof-of-principle study of sonobactericide.
AB  - Infective endocarditis (IE) is associated with high morbidity and mortality
      rates. The predominant bacteria causing IE is Staphylococcus aureus (S. aureus),
      which can bind to existing thrombi on heart valves and generate vegetations
      (biofilms). In this in vitro flow study, we evaluated sonobactericide as a novel
      strategy to treat IE, using ultrasound and an ultrasound contrast agent with or
      without other therapeutics. We developed a model of IE biofilm using human whole
      blood clots infected with patient-derived S. aureus (infected clots). Histology
      and live-cell imaging revealed a biofilm layer of fibrin-embedded living
      Staphylococci around a dense erythrocyte core. Infected clots were treated under
      flow for 30 minutes and degradation was assessed by time-lapse microscopy
      imaging. Treatments consisted of either continuous plasma flow alone or with
      different combinations of therapeutics: oxacillin (antibiotic), recombinant
      tissue plasminogen activator (rt-PA; thrombolytic), intermittent continuous-wave
      low-frequency ultrasound (120-kHz, 0.44 MPa peak-to-peak pressure), and an
      ultrasound contrast agent (Definity). Infected clots exposed to the combination
      of oxacillin, rt-PA, ultrasound, and Definity achieved 99.3 +/- 1.7% loss, which
      was greater than the other treatment arms. Effluent size measurements suggested
      low likelihood of emboli formation. These results support the continued
      investigation of sonobactericide as a therapeutic strategy for IE.

PMID- 29467476
TI  - A Simple 3-Parameter Model for Cancer Incidences.
AB  - We propose a simple 3-parameter model that provides very good fits for incidence
      curves of 18 common solid cancers even when variations due to different
      locations, races, or periods are taken into account. From a data perspective, we
      use model selection (Akaike information criterion) to show that this model, which
      is based on the Weibull distribution, outperforms other simple models like the
      Gamma distribution. From a modeling perspective, the Weibull distribution can be
      justified as modeling the accumulation of driver events, which establishes a link
      to stem cell division based cancer development models and a connection to a
      recursion formula for intrinsic cancer risk published by Wu et al. For the
      recursion formula a closed form solution is given, which will help to simplify
      future analyses. Additionally, we perform a sensitivity analysis for the
      parameters, showing that two of the three parameters can vary over several orders
      of magnitude. However, the shape parameter of the Weibull distribution, which
      corresponds to the number of driver mutations required for cancer onset, can be
      robustly estimated from epidemiological data.

PMID- 29467477
TI  - Microsecond dark-exciton valley polarization memory in two-dimensional
      heterostructures.
AB  - Transition metal dichalcogenides have valley degree of freedom, which features
      optical selection rule and spin-valley locking, making them promising for
      valleytronics devices and quantum computation. For either application, a long
      valley polarization lifetime is crucial. Previous results showed that it is
      around picosecond in monolayer excitons, nanosecond for local excitons and tens
      of nanosecond for interlayer excitons. Here we show that the dark excitons in two
      dimensional heterostructures provide a microsecond valley polarization memory
      thanks to the magnetic field induced suppression of valley mixing. The lifetime
      of the dark excitons shows magnetic field and temperature dependence. The long
      lifetime and valley polarization lifetime of the dark exciton in two-dimensional
      heterostructures make them promising for long-distance exciton transport and
      macroscopic quantum state generations.

PMID- 29467479
TI  - Flat epithelial atypia in directional vacuum-assisted biopsy of breast
      microcalcifications: surgical excision may not be necessary.
AB  - The aim of this study was to analyze the clinicopathological features of patients
      with flat epithelial atypia, diagnosed in directional vacuum-assisted biopsy
      targeting microcalcifications, to identify upgrade rate to in situ ductal or
      invasive breast carcinoma, and determine factors predicting carcinoma in the
      subsequent excision. We retrospectively evaluated the histological, clinical, and
      mammographic features of 69 cases from 65 women, with directional vacuum-assisted
      biopsy-diagnosed flat epithelial atypia with or without atypical ductal
      hyperplasia or atypical lobular hyperplasia, which underwent subsequent surgical
      excision. The extent and percentage of microcalcifications sampled by directional
      vacuum-assisted biopsy were evaluated by mammography. All biopsy and surgical
      excision slides were reviewed. The age of the women ranged from 40 to 85 years
      (mean 57 years). All patients presented with mammographically detected
      microcalcifications only, except in one case that had associated architectural
      distortion. Extent of calcifications ranged from <1 cm (n = 47), 1-3 cm (n = 15)
      to > 3 cm (n = 6), and no measurement (n = 1). A mean of 11 cores (range 6-25)
      was obtained from each lesion. Post-biopsy mammogram revealed >90% removal of
      calcifications in 81% of cases. Pure flat epithelial atypia represented nearly
      two-thirds of directional vacuum-assisted biopsy specimens (n = 43, 62%), while
      flat epithelial atypia coexisted with atypical ductal hyperplasia (18 cases,
      26%), or atypical lobular hyperplasia (8 cases, 12%). Upon excision, none of the
      cases were upgraded to in situ ductal or invasive breast cancer. In one case,
      however, an incidental, tubular carcinoma (4 mm) was found away from biopsy site.
      Excluding this case, the upgrade rate was 0%. Our study adds to the growing
      evidence that diagnosis of flat epithelial atypia on directional vacuum-assisted
      biopsy for microcalcifications as the only imaging finding is not associated with
      a significant upgrade to carcinoma on excision, and therefore, excision may not
      be necessary. Additionally, excision may not be necessary for flat epithelial
      atypia with atypical ductal hyperplasia limited to <=2 terminal duct-lobular
      units, if at least 90% of calcifications have been removed on biopsy.

PMID- 29467478
TI  - Reappraisal of HER2 status in the spectrum of advanced urothelial carcinoma: a
      need of guidelines for treatment eligibility.
AB  - Although human epidermal growth factor receptor 2 (HER2) may represent a
      therapeutic target, its evaluation in urothelial carcinoma of the bladder does
      not rely on a standardized scoring system by immunohistochemistry or fluorescent
      in situ hybridization (FISH), as reflected by various methodology in the
      literature and clinical trials. Our aim was to improve and standardize HER2
      amplification detection in bladder cancer. We assessed immunohistochemical
      criteria derived from 2013 American Society of Clinical Oncology (ASCO)/College
      of American Pathologists (CAPs) guidelines for breast cancer and investigated
      intratumoral heterogeneity in a retrospective multicentric cohort of 188 patients
      with locally advanced urothelial carcinoma of the bladder. Immunohistochemistry
      was performed on 178 primary tumors and 126 lymph node metastases, eligible cases
      (moderate/strong, complete/incomplete membrane staining) were assessed by FISH.
      HER2 overexpression was more frequent with 2013 ASCO/CAP than 2007 ASCO/CAP
      guidelines (p < 0.0001). The rate of positive HER2 FISH was similar between
      primary tumor and lymph node metastases (8%). Among positive FISH cases, 48% were
      associated with moderate/strong incomplete membrane staining that were not scored
      eligible for FISH by 2007 ASCO/CAP criteria. Among 3+ immunohistochemistry score
      cases, 67% were associated with HER2-positive FISH. Concordance between primary
      tumors and matched lymph node metastases was moderate for immunohistochemistry
      (kappa = 0.54 (CI 95%, 0.41-0.67)) and FISH (kappa = 0.50 (CI 95%, 0.20-0.79)).
      HER2-positive FISH was more frequent in micropapillary carcinomas (12%) and
      carcinoma with squamous differentiation (11%) than in pure conventional carcinoma
      (6%). Intratumoral heterogeneity for HER2 immunohistochemistry was observed in 7%
      primary tumor and 6% lymph node metastases; 24% positive HER2 FISH presented
      intratumoral heterogeneity. Our study suggests that HER2 evaluation should
      include an immunohistochemistry screening step with eligibility for FISH
      including incomplete/complete and moderate/strong membrane staining. Spatial or
      temporal intratumoral heterogeneity prompts to perform evaluation on both tumor
      and lymph node, and for each histological variant observed.

PMID- 29467480
TI  - Adenoid cystic carcinomas of the salivary gland, lacrimal gland, and breast are
      morphologically and genetically similar but have distinct microRNA expression
      profiles.
AB  - Adenoid cystic carcinoma is among the most frequent malignancies in the salivary
      and lacrimal glands and has a grave prognosis characterized by frequent local
      recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid
      cystic carcinoma of the breast is a rare type of triple-negative (estrogen and
      progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other
      triple-negative and basal-like breast carcinomas has a very favorable prognosis.
      Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions
      involving MYB, MYBL1, and NFIB, and the reason for the different clinical
      outcomes is unknown. In order to identify the molecular mechanisms underlying the
      discrepancy in clinical outcome, we characterized the phenotypic profiles,
      pattern of gene rearrangements, and global microRNA expression profiles of 64
      salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All
      breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal
      like phenotypes, while salivary gland tumors were indeterminate in 13% of cases.
      Aberrations in MYB and/or NFIB were found in the majority of cases in all three
      locations, whereas MYBL1 involvement was restricted to tumors in the salivary
      gland. Global microRNA expression profiling separated salivary and lacrimal gland
      adenoid cystic carcinoma from their respective normal glands but could not
      distinguish normal breast adenoid cystic carcinoma from normal breast tissue.
      Hierarchical clustering separated adenoid cystic carcinomas of salivary gland
      origin from those of the breast and placed lacrimal gland carcinomas in between
      these. Functional annotation of the microRNAs differentially expressed between
      salivary gland and breast adenoid cystic carcinoma showed these as regulating
      genes involved in metabolism, signal transduction, and genes involved in other
      cancers. In conclusion, microRNA dysregulation is the first class of molecules
      separating adenoid cystic carcinoma according to the site of origin. This
      highlights a novel venue for exploring the biology of adenoid cystic carcinoma.

PMID- 29467481
TI  - The mechanistic causes of peripheral intravenous catheter failure based on a
      parametric computational study.
AB  - Peripheral intravenous catheters (PIVCs) are the most commonly used invasive
      medical device, yet up to 50% fail. Many pathways to failure are mechanistic and
      related to fluid mechanics, thus can be investigated using computational fluid
      dynamics (CFD). Here we used CFD to investigate typical PIVC parameters (infusion
      rate, catheter size, insertion angle and tip position) and report the hemodynamic
      environment (wall shear stress (WSS), blood damage, particle residence time and
      venous stasis volumes) within the vein and catheter, and show the effect of each
      PIVC parameter on each hemodynamic measure. Catheter infusion rate has the
      greatest impact on our measures, with catheter orientation also playing a
      significant role. In some PIVC configurations WSS was 3254 times higher than the
      patent vein, and blood damage was 512 times greater, when compared to control
      conditions. Residence time is geometry-dependent and decreases exponentially with
      increasing insertion angle. Stasis volume decreased with increasing infusion rate
      and, to a lesser degree, insertion angle. Even without infusion, the presence of
      the catheter changes the flow field, causing low velocity recirculation at the
      catheter tip. This research demonstrates how several controllable factors impact
      important mechanisms of PIVC failure. These data, the first of their kind,
      suggest limiting excessive infusion rates in PIVC.

PMID- 29467482
TI  - Synthetic dimensions in ultracold polar molecules.
AB  - Synthetic dimensions alter one of the most fundamental properties in nature, the
      dimension of space. They allow, for example, a real three-dimensional system to
      act as effectively four-dimensional. Driven by such possibilities, synthetic
      dimensions have been engineered in ongoing experiments with ultracold matter. We
      show that rotational states of ultracold molecules can be used as synthetic
      dimensions extending to many - potentially hundreds of - synthetic lattice sites.
      Microwaves coupling rotational states drive fully controllable synthetic inter
      site tunnelings, enabling, for example, topological band structures. Interactions
      leads to even richer behavior: when molecules are frozen in a real space lattice
      with uniform synthetic tunnelings, dipole interactions cause the molecules to
      aggregate to a narrow strip in the synthetic direction beyond a critical
      interaction strength, resulting in a quantum string or a membrane, with an
      emergent condensate that lives on this string or membrane. All these phases can
      be detected using local measurements of rotational state populations.

PMID- 29467483
TI  - Clove Bud Oil Modulates Pathogenicity Phenotypes of the Opportunistic Human
      Pathogen Pseudomonas aeruginosa.
AB  - Earlier studies from our laboratory have demonstrated that clove bud oil (CBO)
      attenuates expression of certain virulence factors of Pseudomonas aeruginosa
      PAO1. Here, we probe more deeply into the effect of CBO on four pseudomonal
      proteases - elastase A, elastase B, protease IV and alkaline protease - each
      known to play key roles in disease pathogenesis. CBO inhibited the activity of
      these proteases present in the bacterial culture supernatant. Zymography studies
      indicated that these proteases can activate host matrix metalloproteases (MMPs)
      to establish infection, through conversion of pro-MMP-2 to active MMP-2. PAO1 is
      a predominant pathogen in burn wound infections and we show the modulatory effect
      of CBO on MMPs in an in vitro model of burn injury. Furthermore, CBO induced dose
      dependent neutrophil extracellular trap formation in human neutrophils. CBO also
      increased the survival of C. elegans infected with PAO1, establishing an anti
      infective role in a whole animal model of pathogenesis. LC-MS/MS analysis
      indicated that CBO treatment elicited a significant reduction of signalling
      molecules (Acyl-Homoserine-Lactone) involved in quorum sensing regulation. Our
      observations demonstrate that CBO attenuates key virulence mechanisms of this
      important human pathogen, while concomitantly enhancing host innate
      immunomodulatory functions, with potential implications for topical therapy
      against antibiotic-resistant infections.

PMID- 29467484
TI  - We skip to work: alternative splicing in normal and malignant myelopoiesis.
AB  - Alternative splicing expands the transcriptome thereby promoting protein
      diversity. It governs critical cellular processes such as differentiation,
      proliferation and apoptosis in a tissue-specific manner. Aberrant splicing
      consequent to mutations in splicing factors and disruption of isoform ratios in
      key regulatory genes provides an important contribution to the pathogenesis of
      the myelodysplastic syndromes and myeloid leukemia. We review here the central
      role of alternative splicing in regulating myelopoiesis, and provide clear
      examples of how global splicing disruption or specific aberrant splicing events
      might promote leukemogenesis. We discuss the growing number of mechanistic links
      between epigenetic factors and alternative splicing. Finally, we address the
      potential utility of alternatively spliced isoforms as biomarkers and the
      development of novel therapies that modulate alternative splicing in myeloid and
      other malignancies.

PMID- 29467485
TI  - The cell fate determinant Scribble is required for maintenance of hematopoietic
      stem cell function.
AB  - Cell fate determinants influence self-renewal potential of hematopoietic stem
      cells. Scribble and Llgl1 belong to the Scribble polarity complex and reveal
      tumor-suppressor function in drosophila. In hematopoietic cells, genetic
      inactivation of Llgl1 leads to expansion of the stem cell pool and increases self
      renewal capacity without conferring malignant transformation. Here we show that
      genetic inactivation of its putative complex partner Scribble results in
      functional impairment of hematopoietic stem cells (HSC) over serial
      transplantation and during stress. Although loss of Scribble deregulates
      transcriptional downstream effectors involved in stem cell proliferation, cell
      signaling, and cell motility, these effectors do not overlap with transcriptional
      targets of Llgl1. Binding partner analysis of Scribble in hematopoietic cells
      using affinity purification followed by mass spectometry confirms its role in
      cell signaling and motility but not for binding to polarity modules described in
      drosophila. Finally, requirement of Scribble for self-renewal capacity also
      affects leukemia stem cell function. Thus, Scribble is a regulator of adult HSCs,
      essential for maintenance of HSCs during phases of cell stress.

PMID- 29467486
TI  - ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia
      update on methodological approaches and results interpretation.
AB  - In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the
      17p13 locus and/or mutation(s) within the TP53 gene, are associated with
      resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On
      these grounds, analysis of TP53 aberrations has been incorporated into routine
      clinical diagnostics to improve patient stratification and optimize therapeutic
      decisions. The predictive implications of TP53 aberrations have increasing
      significance in the era of novel targeted therapies, i.e., inhibitors of B-cell
      receptor (BcR) signaling and anti-apoptotic BCL2 family members, owing to their
      efficacy in patients with TP53 defects. In this report, the TP53 Network of the
      European Research Initiative on Chronic Lymphocytic Leukemia (ERIC) presents
      updated recommendations on the methodological approaches for TP53 mutation
      analysis. Moreover, it provides guidance to ensure that the analysis is performed
      in a timely manner for all patients requiring treatment and that the data is
      interpreted and reported in a consistent, standardized, and accurate way. Since
      next-generation sequencing technologies are gaining prominence within diagnostic
      laboratories, this report also offers advice and recommendations for the
      interpretation of TP53 mutation data generated by this methodology.

PMID- 29467487
TI  - Loss of heterozygosity as a marker of homologous repair deficiency in multiple
      myeloma: a role for PARP inhibition?
AB  - PARP inhibitors can induce synthetic lethality in tumors characterized by
      homologous recombination deficiency (HRD), which can be detected by evaluating
      genome-wide loss of heterozygosity (LOH). Multiple myeloma (MM) is a genetically
      unstable tumor and we hypothesized that HRD-related LOH (HRD-LOH) could be
      detected in patient samples, supporting a potential role for PARP inhibition in
      MM. Using results from targeted next-generation sequencing studies
      (FoundationOne(r) Heme), we analyzed HRD-LOH in patients at all disease stages
      (MGUS (n = 7), smoldering MM (SMM, n = 30), newly diagnosed MM (NDMM, n = 71),
      treated MM (TRMM, n = 64), and relapsed MM (RLMM, n = 234)) using an algorithm to
      identify HRD-LOH segments. We demonstrated HRD-LOH in MM samples, increasing as
      disease progresses. The extent of genomic HRD-LOH correlated with high-risk
      disease markers. Outcome of RLMM patients, the biggest clinical group, was
      analyzed and patients with HRD-LOH above the third quartile (>=5% HRD-LOH) had
      significantly worse progression-free and overall survival than those with lower
      levels (p < 0.001). Mutations in key homologous recombination genes account for
      some, but not all, of the cases with an excess of HRD-LOH. These data support the
      further evaluation of PARP inhibitors in MM patients, particularly in the
      relapsed setting with a high unmet need for new treatments.

PMID- 29467488
TI  - ANP32A regulates histone H3 acetylation and promotes leukemogenesis.
AB  - Deregulation of key regulators of histone modification is important in the
      initiation and progression of human leukemia. Acidic leucine-rich nuclear
      phosphoprotein-32A (ANP32A) participates in histone acetylation and its role in
      acute myeloid leukemia remains unclear. Here we observed significant upregulation
      of ANP32A in primary AML cells, which was essential for AML cell proliferation,
      survival, and colony formation. Integrative analysis of the genome-wide histone
      H3 acetylation and gene expression demonstrated that ANP32A deficiency reduced
      histone H3 acetylation, in accordance with changes in gene expression. Notably,
      significant histone H3 acetylation enrichment was associated with mRNA changes in
      lipid-related genes, including APOC1, PCSK9, P2RX1, and LPPR3. Indeed, over
      expression of APOC1 partially compensated the proliferation-defect phenotype in
      ANP32A deficient AML cells while APOC1 knockdown alone mimicked the effect of
      ANP32A deficiency. Collectively, our data indicate that ANP32A is a novel
      regulator of histone H3 acetylation and promotes leukemogenesis.

PMID- 29467489
TI  - A human bone marrow mesodermal-derived cell population with hemogenic potential.
AB  - The presence, within the human bone marrow, of cells with both endothelial and
      hemogenic potential has been controversial. Herein, we identify, within the human
      fetal bone marrow, prior to establishment of hematopoiesis, a unique APLNR+, Stro
      1+ cell population, co-expressing markers of early mesodermal precursors and/or
      hemogenic endothelium. In adult marrow, cells expressing similar markers are also
      found, but at very low frequency. These adult-derived cells can be extensively
      culture expanded in vitro without loss of potential, they preserve a biased
      hemogenic transcriptional profile, and, upon in vitro induction with OCT4, assume
      a hematopoietic phenotype. In vivo, these cells, upon transplantation into a
      fetal microenvironment, contribute to the vasculature, and generate hematopoietic
      cells that provide multilineage repopulation upon serial transplantation. The
      identification of this human somatic cell population provides novel insights into
      human ontogenetic hematovascular potential, which could lead to a better
      understanding of, and new target therapies for, malignant and nonmalignant
      hematologic disorders.

PMID- 29467490
TI  - Targeting MYC in multiple myeloma.
AB  - Multiple myeloma (MM) is a plasma cell tumor marked by clonal evolution and
      preceded by a premalignant stage, which progresses via molecular pathway
      deregulation, including MYC activation. This activation relates to translocation
      or gain of the MYC locus and deregulation of upstream pathways such as IRF4,
      DIS3/LIN28B/let-7, or MAPK. Precision medicine is an approach to predict more
      accurately which treatment strategies for a particular disease will work in which
      groups of patients, in contrast to a "one-size-fits-all" approach. The knowledge
      of mechanisms responsible for MYC deregulation in MM enables identification of
      vulnerabilities and therapeutic targets in MYC-driven tumors. MYC can be targeted
      directly or indirectly, by interacting with several of its functions in cancer.
      Several such therapeutic strategies are evaluated in clinical trials in MM. In
      this review, we describe the mechanism of MYC activation in MM, the role of MYC
      in cancer progression, and the therapeutic options to targeting MYC.

PMID- 29467491
TI  - MYC-containing amplicons in acute myeloid leukemia: genomic structures,
      evolution, and transcriptional consequences.
AB  - Double minutes (dmin), homogeneously staining regions, and ring chromosomes are
      vehicles of gene amplification in cancer. The underlying mechanism leading to
      their formation as well as their structure and function in acute myeloid leukemia
      (AML) remain mysterious. We combined a range of high-resolution genomic methods
      to investigate the architecture and expression pattern of amplicons involving
      chromosome band 8q24 in 23 cases of AML (AML-amp). This revealed that different
      MYC-dmin architectures can coexist within the same leukemic cell population,
      indicating a step-wise evolution rather than a single event origin, such as
      through chromothripsis. This was supported also by the analysis of the
      chromothripsis criteria, that poorly matched the model in our samples.
      Furthermore, we found that dmin could evolve toward ring chromosomes stabilized
      by neocentromeres. Surprisingly, amplified genes (mainly PVT1) frequently
      participated in fusion transcripts lacking a corresponding DNA template. We also
      detected a significant overexpression of the circular RNA of PVT1 (circPVT1) in
      AML-amp cases versus AML with a normal karyotype. Our results show that 8q24
      amplicons in AML are surprisingly plastic DNA structures with an unexpected
      association to novel fusion transcripts and circular RNAs.

PMID- 29467492
TI  - The HDAC inhibitor SAHA regulates CBX2 stability via a SUMO-triggered ubiquitin
      mediated pathway in leukemia.
AB  - Polycomb group (PcG) proteins regulate transcription, playing a key role in
      stemness and differentiation. Deregulation of PcG members is known to be involved
      in cancer pathogenesis. Emerging evidence suggests that CBX2, a member of the PcG
      protein family, is overexpressed in several human tumors, correlating with lower
      overall survival. Unraveling the mechanisms regulating CBX2 expression may thus
      provide a promising new target for anticancer strategies. Here we show that the
      HDAC inhibitor SAHA regulates CBX2 stability via a SUMO-triggered ubiquitin
      mediated pathway in leukemia. We identify CBX4 and RNF4 as the E3 SUMO and E3
      ubiquitin ligase, respectively, and describe the specific molecular mechanism
      regulating CBX2 protein stability. Finally, we show that CBX2-depleted leukemic
      cells display impaired proliferation, underscoring its critical role in
      regulating leukemia cell tumorogenicity. Our results show that SAHA affects CBX2
      stability, revealing a potential SAHA-mediated anti-leukemic activity though
      SUMO2/3 pathway.

PMID- 29467493
TI  - c-Jun/AP-1 overexpression reprograms ERalpha signaling related to tamoxifen
      response in ERalpha-positive breast cancer.
AB  - A critical mechanism that has been proposed for transcription regulation by
      estrogen receptor alpha (ER) is the tethering of ER to DNA via other
      transcription factors, such as AP-1. However, genome-wide assessment of the
      overlap in chromatin binding repertoires of these two transcription factors has
      not been reported. Here, we show that the AP-1 transcription factor c-Jun
      interacts with ER and that c-Jun chromatin binding shows extensive overlap with
      ER binding at the global level. Further, we show that c-Jun overexpression
      reprograms ER chromatin binding and modulates ER-mediated gene regulation. Our
      data are consistent with a mechanism where estrogen/ER-dependent crosstalk with
      AP-1 at the transcriptional level is mediated through the tethering of ER to DNA
      bound AP-1. Additionally, in our system c-Jun overexpression causes reduced
      sensitivity to tamoxifen in ER+ breast cancer cells. Integrated cistrome,
      transcriptome, and clinical data reveal TGFBI as a candidate gene which may
      confer tamoxifen resistance by ER and AP-1 crosstalk. Further, we show that TGFBI
      expression is elevated in breast cancer compared to normal breast. Together, our
      data provide a novel genome-wide footprint of ER and AP-1 crosstalk and suggest
      AP-1 and TGFBI signaling as potential therapeutic targets in AP-1-overexpressing
      ER-positive breast tumors.

PMID- 29467494
TI  - Alternative transcription of a shorter, non-anti-angiogenic thrombospondin-2
      variant in cancer-associated blood vessels.
AB  - Thrombospondin-2 (TSP2) is an anti-angiogenic matricellular protein that inhibits
      tumor growth and angiogenesis. Tumor-associated blood vascular endothelial cells
      (BECs) were isolated from human invasive bladder cancers and from matched normal
      bladder tissue by immuno-laser capture microdissection. Exon expression profiling
      analyses revealed a particularly high expression of a short TSP2 transcript
      containing only the last 9 (3') exons of the full-length TSP2 transcript. Using
      5' and 3' RACE (rapid amplification of cDNA ends) and Sanger sequencing, we
      confirmed the existence of the shorter transcript of TSP2 (sTSP2) and determined
      its sequence which completely lacked the anti-angiogenic thrombospondin type 1
      repeats domain. The largest open reading frame predicted within the transcript
      comprises 209 amino acids and matches almost completely the C-terminal lectin
      domain of full-length TSP2. We produced recombinant sTSP2 and found that unlike
      the full-length TSP2, sTSP2 did not inhibit vascular endothelial growth factor-A
      induced proliferation of cultured human BECs, but in contrast when combined with
      TSP2 blocked the inhibitory effects of TSP2 on BEC proliferation. In vivo studies
      with stably transfected A431 squamous cell carcinoma cells revealed that full
      length TSP2, but not sTSP2, inhibited tumor growth and angiogenesis. This study
      reveals that the transcriptional program of tumor stromal cells can change to
      transcribe a new version of an endogenous angiogenesis inhibitor that has lost
      its anti-angiogenic activity.

PMID- 29467495
TI  - Representations of naturalistic stimulus complexity in early and associative
      visual and auditory cortices.
AB  - The complexity of sensory stimuli has an important role in perception and
      cognition. However, its neural representation is not well understood. Here, we
      characterize the representations of naturalistic visual and auditory stimulus
      complexity in early and associative visual and auditory cortices. This is
      realized by means of encoding and decoding analyses of two fMRI datasets in the
      visual and auditory modalities. Our results implicate most early and some
      associative sensory areas in representing the complexity of naturalistic sensory
      stimuli. For example, parahippocampal place area, which was previously shown to
      represent scene features, is shown to also represent scene complexity. Similarly,
      posterior regions of superior temporal gyrus and superior temporal sulcus, which
      were previously shown to represent syntactic (language) complexity, are shown to
      also represent music (auditory) complexity. Furthermore, our results suggest the
      existence of gradients in sensitivity to naturalistic sensory stimulus complexity
      in these areas.

PMID- 29467496
TI  - Trends in seasonal warm anomalies across the contiguous United States:
      Contributions from natural climate variability.
AB  - Many studies have shown the importance of anthropogenic greenhouse gas emissions
      in contributing to observed upward trends in the occurrences of temperature
      extremes over the U.S. However, few studies have investigated the contributions
      of internal variability in the climate system to these observed trends. Here we
      use daily maximum temperature time series from the North American Land Data
      Assimilation System Phase 2 (NLDAS-2) dataset to identify trends in seasonal warm
      anomalies over the contiguous U.S. in the three most recent decades and explore
      their relationships to low-frequency modes of internal climate variability. The
      results reveal substantial upward trends in the frequency of warm anomalies in
      all seasons and in all regions of the U.S., except for portions of the
      Intermountain West in winter where significant downward trends occur. The
      strengths and regional coverage of the trends, however, differ considerably by
      season. These trends can be explained, in part, by the large-scale anomalous
      atmospheric circulations associated with low-frequency sea-surface temperature
      oscillations characterized by the Pacific Decadal Oscillation (PDO) and the
      Atlantic Multidecadal Oscillation (AMO). The association between the upward
      trends in the seasonal warm anomalies and PDO and AMO is further confirmed by the
      century-long (1871-2012) Twentieth Century Reanalysis dataset.

PMID- 29467497
TI  - Altered TAOK2 activity causes autism-related neurodevelopmental and cognitive
      abnormalities through RhoA signaling.
AB  - Atypical brain connectivity is a major contributor to the pathophysiology of
      neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs).
      TAOK2 is one of several genes in the 16p11.2 microdeletion region, but whether it
      contributes to NDDs is unknown. We performed behavioral analysis on Taok2
      heterozygous (Het) and knockout (KO) mice and found gene dosage-dependent
      impairments in cognition, anxiety, and social interaction. Taok2 Het and KO mice
      also have dosage-dependent abnormalities in brain size and neural connectivity in
      multiple regions, deficits in cortical layering, dendrite and synapse formation,
      and reduced excitatory neurotransmission. Whole-genome and -exome sequencing of
      ASD families identified three de novo mutations in TAOK2 and functional analysis
      in mice and human cells revealed that all the mutations impair protein stability,
      but they differentially impact kinase activity, dendrite growth, and
      spine/synapse development. Mechanistically, loss of Taok2 activity causes a
      reduction in RhoA activation, and pharmacological enhancement of RhoA activity
      rescues synaptic phenotypes. Together, these data provide evidence that TAOK2 is
      a neurodevelopmental disorder risk gene and identify RhoA signaling as a mediator
      of TAOK2-dependent synaptic development.

PMID- 29467498
TI  - Early Detection of Preeclampsia Using Circulating Small non-coding RNA.
AB  - Preeclampsia is one of the most dangerous pregnancy complications, and the
      leading cause of maternal and perinatal mortality and morbidity. Although the
      clinical symptoms appear late, its origin is early, and hence detection is
      feasible already at the first trimester. In the current study, we investigated
      the abundance of circulating small non-coding RNAs in the plasma of pregnant
      women in their first trimester, seeking transcripts that best separate the
      preeclampsia samples from those of healthy pregnant women. To this end, we
      performed small non-coding RNAs sequencing of 75 preeclampsia and control
      samples, and identified 25 transcripts that were differentially expressed between
      preeclampsia and the control groups. Furthermore, we utilized those transcripts
      and created a pipeline for a supervised classification of preeclampsia. Our
      pipeline generates a logistic regression model using a 5-fold cross validation on
      numerous random partitions into training and blind test sets. Using this
      classification procedure, we achieved an average AUC value of 0.86. These
      findings suggest the predictive value of circulating small non-coding RNA in the
      first trimester, warranting further examination, and lay the foundation for
      producing a novel early non-invasive diagnostic tool for preeclampsia, which
      could reduce the life-threatening risk for both the mother and fetus.

PMID- 29467499
TI  - Coupling a single solid-state quantum emitter to an array of resonant plasmonic
      antennas.
AB  - Plasmon resonant arrays or meta-surfaces shape both the incoming optical field
      and the local density of states for emission processes. They provide large
      regions of enhanced emission from emitters and greater design flexibility than
      single nanoantennas. This makes them of great interest for engineering optical
      absorption and emission. Here we study the coupling of a single quantum emitter,
      a self-assembled semiconductor quantum dot, to a plasmonic meta-surface. We
      investigate the influence of the spectral properties of the nanoantennas and the
      position of the emitter in the unit cell of the structure. We observe a resonant
      enhancement due to emitter-array coupling in the far-field regime and find a
      clear difference from the interaction of an emitter with a single antenna.

PMID- 29467500
TI  - A tomato MADS-box protein, SlCMB1, regulates ethylene biosynthesis and carotenoid
      accumulation during fruit ripening.
AB  - The MADS-box transcription factors play essential roles in many physiological and
      biochemical processes of plants, especially in fruit ripening. Here, a tomato
      MADS-box gene, SlCMB1, was isolated. SlCMB1 expression declined with the fruit
      ripening from immature green to B + 7 (7 days after Breaker) fruits in the wild
      type (WT) and was lower in Nr and rin mutants fruits. Tomato plants with reduced
      SlCMB1 mRNA displayed delayed fruit ripening, reduced ethylene production and
      carotenoid accumulation. The ethylene production in SlCMB1-RNAi fruits decreased
      by approximately 50% as compared to WT. The transcripts of ethylene biosynthesis
      genes (ACS2, ACS4, ACO1 and ACO3), ethylene-responsive genes (E4, E8 and ERF1)
      and fruit ripening-related genes (RIN, TAGL1, FUL1, FUL2, LoxC and PE) were
      inhibited in SlCMB1-RNAi fruits. The carotenoid accumulation was decreased and
      two carotenoid synthesis-related genes (PSY1 and PDS) were down-regulated while
      three lycopene cyclase genes (CYCB, LCYB and LCYE) were up-regulated in
      transgenic fruits. Furthermore, yeast two-hybrid assay showed that SlCMB1 could
      interact with SlMADS-RIN, SlMADS1, SlAP2a and TAGL1, respectively. Collectively,
      these results indicate that SlCMB1 is a new component to the current model of
      regulatory network that regulates ethylene biosynthesis and carotenoid
      accumulation during fruit ripening.

PMID- 29467501
TI  - Parents' considerable underestimation of sugar and their child's risk of
      overweight.
AB  - High sugar intake is associated with an increased risk of overweight. For
      parents, as their children's nutritional gatekeepers, knowledge about sugar is a
      prerequisite for regulating sugar consumption. Yet little is known about parental
      ability to estimate the sugar content of foods and beverages and how this ability
      is associated with children's body mass index (BMI). In 305 parent-child pairs,
      we investigated to what extent parents systematically under- or overestimate the
      sugar content of foods and beverages commonly found in children's diets as well
      as potential associations with children's z-BMI. Parents considerably
      underestimated the sugar content of most foods and beverages (e.g., 92% of
      parents underestimated the sugar content of yogurt by, on average, seven sugar
      cubes). After controlling for parental education and BMI, parental sugar
      underestimation was significantly associated with a higher risk of their child
      being overweight or obese (odds ratio = 2.01). There was a small dose-response
      relationship between the degree of underestimation and the child's z-BMI. These
      findings suggest that providing easily accessible and practicable knowledge about
      sugar content through, for instance, nutritional labeling may improve parents'
      intuition about sugar. This could help curtail sugar intake in children and thus
      be a preventive measure for overweight.

PMID- 29467503
TI  - Optimism for Africa.

PMID- 29467502
TI  - CDH13 abundance interferes with adipocyte differentiation and is a novel
      biomarker for adipose tissue health.
AB  - BACKGROUND: CDH13, an atypical member of the cadherin superfamily, has been
      identified in adipocyte secretomes of lean mouse models. CDH13 abundance differs
      in mouse models according to their susceptibility to develop metabolic disorders,
      but the role of CDH13 in adipose tissue is unknown. METHODS: Secreted CDH13
      protein levels and mRNA levels in visceral adipose tissue were determined in lean
      and obese mouse models. In vitro studies were performed in 3T3-L1 adipocytes to
      determine the role of CDH13 in adipocyte differentiation. The pathophysiological
      impact of visceral adipose tissue CDH13 mRNA and circulating CDH13 levels were
      determined in humans (normal-weight men n = 37, obese men n = 109 including n =
      51 type 2 diabetes patients) and in obese patients (n = 14) pre- and post
      metabolic surgery. RESULTS: This study shows that in visceral adipose tissue
      CDH13 protein secretion and mRNA levels were decreased in obese mouse models.
      Mechanistically, CDH13 affects lipid metabolism during adipogenesis but not in
      mature adipocytes. CDH13 knockdown during adipogenesis reduced fatty acid uptake
      and lipid content in developing adipocytes. Furthermore, CDH13 depletion during
      adipogenesis lowered the induction of PPARgamma and C/EBPalpha expression. These
      observations are of pathophysiological impact since visceral adipose tissue CDH13
      mRNA and circulating CDH13 levels were decreased in obese men compared to normal
      weight controls. Weight loss induced by bariatric surgery restored circulating
      CDH13 to levels found in normal-weight controls. CONCLUSIONS: CDH13 levels in
      adipose tissue and the circulation are affected by obesity in mouse models and
      humans and are restored by weight loss in humans. CDH13 interferes with the
      differentiation potential of adipocytes and therefore is a marker for plasticity
      of fat tissue that might reflect the health status of adipose tissue.

PMID- 29467505
TI  - Still seeking coherence.

PMID- 29467504
TI  - Imaging the atomic structure and local chemistry of platelets in natural type Ia
      diamond.
AB  - In the past decades, many efforts have been devoted to characterizing {001}
      platelet defects in type Ia diamond. It is known that N is concentrated at the
      defect core. However, an accurate description of the atomic structure of the
      defect and the role that N plays in it is still unknown. Here, by using
      aberration-corrected transmission electron microscopy and electron energy-loss
      spectroscopy we have determined the atomic arrangement within platelet defects in
      a natural type Ia diamond and matched it to a prevalent theoretical model. The
      platelet has an anisotropic atomic structure with a zigzag ordering of defect
      pairs along the defect line. The electron energy-loss near-edge fine structure of
      both carbon K- and nitrogen K-edges obtained from the platelet core is consistent
      with a trigonal bonding arrangement at interstitial sites. The experimental
      observations support an interstitial aggregate mode of formation for platelet
      defects in natural diamond.

PMID- 29467506
TI  - A thirst for advancement.

PMID- 29467507
TI  - Resolving the controversy.

PMID- 29467508
TI  - Effect of the environment microbiota on the flavour of light-flavour Baijiu
      during spontaneous fermentation.
AB  - Light-flavour Baijiu is a type of Chinese liquor with a pure and mild flavour
      produced by traditional spontaneous solid-state fermentation. The flavour of this
      liquor has been found to vary in the different periods of annual production. To
      explore the factors affecting flavour, the microbiota of the surrounding
      environment, starter and fermentation process in different periods were
      investigated. Results showed that the ester content and acidity of light-flavour
      Baijiu were significantly lower when annual production was resumed after a summer
      break. HCA plot of volatile flavour profile and bacterial PCoA results indicated
      that the differences occurred at later stages, mainly due to different structures
      of Lactobacillus. Correlation analysis by O2PLS indicated that Lactobacillus
      positively correlated with esters. Species-level analysis showed that the lack of
      L. acetotolerans on the surface of the jar might cause a lag in fermentation and
      lower ester content. Thereafter, L. acetotolerans was revived during fermentation
      and enriched on the surface of the jar, which promoted ester formation. As
      important sources of L. acetotolerans, the air and fermentation jars played a
      critical role during fermentation. Therefore, this systematic study on
      environmental microbial ecology is valuable for quality control and to explore
      environmental microbiota functions during spontaneous fermentation.

PMID- 29467509
TI  - Magnesium enhances the chondrogenic differentiation of mesenchymal stem cells by
      inhibiting activated macrophage-induced inflammation.
AB  - Magnesium deficiency increases the generation of pro-inflammatory cytokines,
      which is consistently accompanied by the sensitization of cells such as
      neutrophils, macrophages and endothelial cells. We investigated the potential of
      magnesium to regulate macrophage polarization and macrophage-induced inflammation
      with or without lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)
      activation and further elucidated whether these effects impact the inhibitory
      functions of activated macrophage-induced inflammation on cartilage regeneration.
      The results showed that magnesium inhibited the activation of macrophages, as
      indicated by a significant reduction in the percentage of CCR7-positive cells,
      while the percentage of CD206-positive cells decreased to a lesser degree. After
      activation, both pro-inflammatory and anti-inflammatory cytokines were down
      regulated at the mRNA level and certain cytokines (IL-1beta, IL-6 and IL-10) were
      decreased in the cell supernatant with the addition of magnesium. Moreover,
      magnesium decreased the nuclear translocation and phosphorylation of nuclear
      factor-kappaB (NF-kappaB) to impede its activation. A modified micromass culture
      system was applied to assess the effects of activated macrophage-conditioned
      medium with or without magnesium treatment on the chondrogenic differentiation of
      human bone marrow mesenchymal stem cells (hBMSCs). Magnesium enhanced the
      chondrogenic differentiation of hBMSCs by reversing the adverse effects of
      activated macrophage-induced inflammation.

PMID- 29467510
TI  - Three dimensional metal/N-doped nanoplate carbon catalysts for oxygen reduction,
      the reason for using a layered nanoreactor.
AB  - A layered nanoreactor (zinc hydroxide gallate/nitrate nanohybrid) has been
      designed as a nano-vessel to confine the gallate/nitrate reaction inside zinc
      hydroxide layers for production of metal/nitrogen-doped carbon catalysts. Metals
      (Fe2+, Co2+ and Ni2+) doped and bare zinc hydroxide nitrates (ZHN) were
      synthesized as the alpha-phase hydroxide hosts. By an incomplete ion-exchange
      process, nitrate anions between the layers of the hosts were then partially
      replaced by the gallate anions to produce the layered nanoreactors. Under heat
      treatment, the reaction between the remaining un-exchanged nitrate anions and the
      organic moiety inside the basal spacing of each nanohybrid plate resulted in
      obtaining highly porous 3D metal/nitrogen-doped carbon nanosheets. These
      catalysts were then used as extremely efficient electrocatalysts for catalyzing
      oxygen reduction reaction (ORR). This study is intended to show the way to get
      maximum electrocatalytic activity of the metal/N-doped carbon catalysts toward
      the ORR. This exceptionally high ORR performance originates from the increased
      available surface, the best pore size range and the uniform distribution of the
      active sites in the produced catalysts, all provided by the use of new idea of
      the layered nanoreactor.

PMID- 29467511
TI  - Difference in anisotropic etching characteristics of alkaline and copper based
      acid solutions for single-crystalline Si.
AB  - The so called inverted pyramid arrays, outperforming conventional upright pyramid
      textures, have been successfully achieved by one-step Cu assisted chemical
      etching (CACE) for light reflection minimization in silicon solar cells. Due to
      the lower reduction potential of Cu2+/Cu and different electronic properties of
      different Si planes, the etching of Si substrate shows orientation-dependent.
      Different from the upright pyramid obtained by alkaline solutions, the formation
      of inverted pyramid results from the coexistence of anisotropic etching and
      localized etching process. The obtained structure is bounded by Si {111} planes
      which have the lowest etching rate, no matter what orientation of Si substrate
      is. The Si etching rate and (100)/(111) etching ratio are quantitatively
      analyzed. The different behaviors of anisotropic etching of Si by alkaline and Cu
      based acid etchant have been systematically investigated.

PMID- 29467512
TI  - Energy storage in structural composites by introducing CNT fiber/polymer
      electrolyte interleaves.
AB  - This work presents a method to produce structural composites capable of energy
      storage. They are produced by integrating thin sandwich structures of CNT fiber
      veils and an ionic liquid-based polymer electrolyte between carbon fiber plies,
      followed by infusion and curing of an epoxy resin. The resulting structure
      behaves simultaneously as an electric double-layer capacitor and a structural
      composite, with flexural modulus of 60 GPa and flexural strength of 153 MPa,
      combined with 88 mF/g of specific capacitance and the highest power (30 W/kg) and
      energy (37.5 mWh/kg) densities reported so far for structural supercapacitors. In
      situ electrochemical measurements during 4-point bending show that
      electrochemical performance is retained up to fracture, with minor changes in
      equivalent series resistance for interleaves under compressive stress. En route
      to improving interlaminar properties we produce grid-shaped interleaves that
      enable mechanical interconnection of plies by the stiff epoxy. Synchrotron 3D X
      ray tomography analysis of the resulting hierarchical structure confirms the
      formation of interlaminar epoxy joints. The manuscript discusses encapsulation
      role of epoxy, demonstrated by charge-discharge measurements of composites
      immersed in water, a deleterious agent for ionic liquids. Finally, we show
      different architectures free of current collector and electrical insulators, in
      which both CNT fiber and CF act as active electrodes.

PMID- 29467513
TI  - Basic research: RNA deadenylation by CCR4-NOT controls heart function.

PMID- 29467514
TI  - Could electrohysterography be the solution for external uterine monitoring in
      obese women?
AB  - OBJECTIVE: To evaluate the influence of maternal obesity on the performance of
      external tocodynamometry and electrohysterography. STUDY DESIGN: In a 2-hour
      measurement during term labor, uterine contractions were simultaneously measured
      by electrohysterography, external tocodynamometry, and intra-uterine pressure
      catheter. The sensitivity was compared between groups based on obesity (non
      obese/obese/morbidly obese) or uterine palpation (good/moderate/poor), and was
      correlated to maternal BMI and abdominal circumference. RESULT: We included 14
      morbidly obese, 18 obese, and 20 non-obese women. In morbidly obese women, the
      median sensitivity was 87.2% (IQR 74-93) by electrohysterography and 45.0% (IQR
      36-66) by external tocodynamometry (p < 0.001). The sensitivity of
      electrohysterography appeared to be non-influenced by obesity category (p =
      0.279) and uterine palpation (p = 0.451), while the sensitivity of
      tocodynamometry decreased significantly (p = 0.005 and p < 0.001, respectively).
      Furthermore, the sensitivity of both external methods was negatively correlated
      with obesity parameters, being non-significant for electrohysterography (range p
      values 0.057-0.088) and significant for external tocodynamometry (all p-values <
      0.001). CONCLUSIONS: Electrohysterography performs significantly better than
      external tocodynamometry in case of maternal obesity.

PMID- 29467515
TI  - Infant size and the association between maternal circulating angiogenic factors
      and preeclampsia.
AB  - OBJECTIVE: To assess the effect of infant size as a marker of placental function
      on the association between preeclampsia and the ratio of soluble fms-like
      tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF). STUDY DESIGN: The
      angiogenic factors sFlt-1 and PlGF were measured prospectively at 26 weeks
      gestation in 2322 women. Pregnancies were stratified by whether or not they were
      complicated by preeclampsia, the timing of delivery, and birthweight Z-score.
      RESULT: Independent of preeclampsia status, women with small infants (Z < -1.0)
      have an increased sFlt-1/PlGF ratio, and women with large infants (Z > 1.0) have
      a decreased ratio. Among pregnancies yielding small infants, the sFlt-1/PlGF
      ratio is markedly elevated in preeclamptic pregnancies requiring delivery before
      37 weeks (110.0 vs. 17.9, p < 0.0001) but not in preeclamptic pregnancies
      delivered at term. The strength of the association between preeclampsia and the
      sFlt-1/PlGF ratio is increased for small infants compared to normal-sized or
      large infants. CONCLUSION: The sFlt-1/PlGF ratio in the late second trimester is
      similarly elevated in women with preeclampsia and in women with small infant size
      and more markedly elevated in a syndrome of placental dysfunction characterized
      by preeclampsia, preterm delivery, and growth restriction.

PMID- 29467516
TI  - Packed red blood cells transfusion in neonates: effect on FiO2 and PaO2/SaO2
      ratio, and implications for neonatal saturation targeting.
AB  - OBJECTIVE: To assess the effect of blood transfusions in neonates on partial
      pressure of oxygen in arterial blood (PaO2), arterial hemoglobin oxygen
      saturation (SaO2) and arterial hemoglobin oxygen saturation as measured by pulse
      oximetry (SpO2). STUDY DESIGN: Retrospective study of neonates that received a
      first blood transfusion while having an indwelling arterial line. We compared
      PaO2, SaO2, SpO2, SaO2/PaO2 ratio and fraction of inspired oxygen (FiO2) 12 h
      before and after blood transfusion. RESULTS: Post-transfusion neonates had higher
      PaO2 and SaO2, had lower SaO2/PaO2 ratio, and received higher FiO2 with no change
      in SpO2. CONCLUSIONS: Post-transfusion, neonates had lower hemoglobin oxygen
      affinity. They received higher FiO2 and had higher PaO2 at the same SpO2. We
      speculate that FiO2 was increased in order to maintain SpO2. Larger prospective
      trials are needed to confirm our findings.

PMID- 29467517
TI  - The death knell of inhaled nitric oxide to prevent bronchopulmonary dysplasia?

PMID- 29467518
TI  - Is umbilical coiling genetically determined?
AB  - OBJECTIVE: Abnormal umbilical cord coiling is associated with adverse perinatal
      outcomes; however, the etiology of the umbilical coiling pattern is poorly
      understood. STUDY DESIGN: Retrospective cohort of all twin deliveries >20 weeks
      in 2014. Pregnancies were dichotomized by chorionicity and the umbilical coiling
      index (UCI) and placental cord insertion location were compared. In cases with
      one or both cords hypercoiled, the direction and pattern of coiling were compared
      by chorionicity. A similar analysis was performed stratified by zygosity.
      RESULTS: Three hundred sisty two twin pairs were included; 26 (7.2%)
      monochorionic and 174 (87.0%) definitively dizygotic. Concordance in the UCI and
      coiling category were similar between dichorionic and monochorionic as well as
      dizygous and monozygous gestations, (73.2% vs 80.8%, p = 0.399 and 71.4% vs
      80.8%, p = 0.399, respectively). Analyses of the coiling direction and pattern
      also demonstrated no difference by chorionicity or zygosity. CONCLUSION: These
      data do not support a genetic basis for umbilical cord coiling.

PMID- 29467519
TI  - Letter to the editor.

PMID- 29467520
TI  - Premedication with paralysis improves intubation success and decreases adverse
      events in very low birth weight infants: a prospective cohort study.
AB  - OBJECTIVE: To characterize the impact of premedication with and without a
      paralytic agent on the safety of tracheal intubation (TI) in infants <=1500 g.
      STUDY DESIGN: A prospective observational cohort study between February 2015 and
      June 2017. The primary outcomes were associations between the use of different
      premedication regimens with number of TI attempts, TI adverse events (TIAEs), and
      changes in heart rate. RESULTS: Data were collected on 237 TIs. Median
      postmenstrual age at intubation was 28 completed weeks and weight was 953 g.
      Premedication with a paralytic was associated with fewer intubation attempts
      compared to premedication without a paralytic (p = 0.037). Premedication with a
      paralytic was associated with fewer TIAEs (p < 0.001) and less bradycardia
      compared to the other two regimens (p = 0.003) compared to premedication without
      a paralytic. CONCLUSIONS: Premedication with a paralytic was associated with
      fewer intubation attempts, fewer TIAEs, and less bradycardia. Premedication with
      a paralytic may improve intubation safety in VLBWs.

PMID- 29467522
TI  - Is early-onset sepsis risk calculator safe for the management of neonates born to
      mothers with chorioamnionitis?

PMID- 29467521
TI  - Rapid resolution of hyperammonemia in neonates using extracorporeal membrane
      oxygenation as a platform to drive hemodialysis.
AB  - OBJECTIVE: We aimed to clarify the impact of extracorporeal membrane oxygenation
      (ECMO) as a platform to drive hemodialysis (HD) for ammonia clearance on outcomes
      of neonates with severe hyperammonemia. STUDY DESIGN: All neonates treated for
      hyperammonemia at a single children's hospital between 1992 and 2016 were
      identified. Patient characteristics and outcomes were compared between those
      receiving medical management or ECMO/HD. RESULT: Twenty-five neonates were
      treated for hyperammonemia, of which 13 (52%) received ECMO/HD. Peak ammonia
      levels among neonates treated with ECMO/HD were significantly higher than those
      medically managed (1041 [IQR 902-1581] MUmol/L versus 212 [IQR 110-410] MUmol/L;
      p = 0.009). Serum ammonia levels in the ECMO/HD cohort declined to the median of
      medically managed within 4.5 (IQR 2.9-7.0) hours and normalized within 7.3 (IQR
      3.6-13.5) hours. All neonates survived ECMO/HD, and nine (69.2%) survived to
      discharge. CONCLUSION: ECMO/HD is an effective adjunct to rapidly clear severe
      hyperammonemia in newborns, reducing potential neurodevelopmental morbidity.

PMID- 29467523
TI  - Early low-dose hydrocortisone: is the neurodevelopment affected?
AB  - TYPE OF INVESTIGATION: Prognosis; exploratory secondary analysis of an
      interventional randomized controlled trial. QUESTION: In extremely preterm infant
      (<28 weeks), is early low-dose hydrocortisone compared to placebo associated with
      neurodevelopmental impairment at 2 years of age? METHODS: Patients: Surviving
      infants enrolled in the PREMILOC trial conducted in France between 2008 and 2014.
      INTERVENTION: Double-blind, multicenter, randomized, placebo-controlled trial of
      infants born between 24 0/7 weeks and 27 6/7 weeks of gestation and before 24 h
      of postnatal age, assigned to receive either placebo or low-dose hydrocortisone
      (0.5 mg/kg twice per day for 7 days, followed by 0.5 mg/kg per day for 3 days).
      MAIN RESULTS: For the pre-specified exploratory outcome, the distribution of
      patients without neurodevelopmental impairment (73% in the hydrocortisone group
      vs. 70% in the placebo group), with mild neurodevelopmental impairment (20% in
      the hydrocortisone group vs. 18% in the placebo group), or with moderate to
      severe neurodevelopmental impairment (7% in the hydrocortisone group vs. 11% in
      the placebo group) was not found to be statistically significantly different
      between the two groups (p = 0.33). Qualitative assessment of patients using
      standardized neurological examination also was not statistically significantly
      different between groups (p = 0.87). STUDY CONCLUSION: In this follow-up study of
      premature infants who were randomly assigned at birth to receive low-dose
      hydrocortisone or placebo for 10 days, hydrocortisone treatment was not
      associated with any adverse effects on neurodevelopmental outcome at 22 months of
      corrected age.

PMID- 29467524
TI  - Breast cancer: Staying silent.

PMID- 29467525
TI  - Genomic instability: The sting of metastasis.

PMID- 29467526
TI  - Tumour microenvironment: Fibroblast subtype provides niche for cancer stem cells.

PMID- 29467527
TI  - Removal of Knotted Percutaneous Endoscopic Jejunostomy Tube.

PMID- 29467528
TI  - Severe Colitis After an Alcohol Enema.

PMID- 29467529
TI  - Editorial: Assessing Esophageal Function in Achalasia: The Old and the New.
AB  - Achalasia is currently diagnosed according to the Chicago Classification v3.0
      using high-resolution manometry and treatment focuses on disruption of the
      esophagogastric junction. A paper in this issue examines the utility of a timed
      barium esophagram with a 13 mm tablet challenge in differentiating achalasia from
      other diagnoses, finding 100% sensitivity. However, a large proportion of
      patients with non-achalasia dysphagia are also identified. Another paper in this
      issue proposes utilizing intraprocedure functional luminal imaging probe
      measurement during pneumatic dilation as a guide for upsizing dilations. This
      appears promising, but prospective validation is necessary before this becomes
      standard of care.

PMID- 29467531
TI  - Continuing Medical Education Questions: February 2018: ACG Clinical Guideline:
      Alcoholic Liver Disease.

PMID- 29467530
TI  - A Case of Panenteritis With Massive IgG4-Positive Plasma Cell Infiltration
      Developed 26 Years After Total Proctocolectomy for Ulcerative Colitis.

PMID- 29467533
TI  - Continuing Medical Education Questions: February 2018: Timed Barium Swallow:
      Diagnostic Role and Predictive Value in Untreated Achalasia, Esophagogastric
      Junction Outflow Obstruction and Non-Achalasia Dysphagia.

PMID- 29467532
TI  - A Completely Occluded Colorectal Anastomotic Stenosis Treated Using an Endoscopic
      Incision Method.

PMID- 29467534
TI  - The Hibernating Bear-A Good Analogy to Explain Why Acute Fatty Liver of Pregnancy
      Manifests in Late Pregnancy.

PMID- 29467535
TI  - An Additional Case of Aortoesophageal Fistula.

PMID- 29467536
TI  - 2017 ACG Presidential Address: Challenges in the Practice of Gastroenterology:
      Engaging with ACG for Positive Impact.

PMID- 29467537
TI  - Acid Control in Barrett's Esophagus: A Plea for Documentation.

PMID- 29467539
TI  - Editorial: Increasing Incidence of Pediatric Inflammatory Bowel Disease in
      France: Implications for Etiology, Diagnosis, Prognosis, and Treatment.
AB  - The significant increase in pediatric-onset inflammatory bowel disease in recent
      decades appears to be a global phenomenon, with studies from multiple geographic
      areas noting an increase in Crohn's disease (CD) and ulcerative colitis (UC). In
      this large, population-based cohort from northern France, the rapid increase in
      pediatric CD and UC from 1988-2011 may be due to multiple potential etiologies
      including environmental factors and advancements in diagnostic capabilities. We
      should consider the clinical implications of this rise in incidence, including
      potential risk stratification approaches that may offer the ability to modify the
      disease course of patients with earlier diagnosis.

PMID- 29467540
TI  - Identification of a novel microRNA-mRNA regulatory biomodule in human prostate
      cancer.
AB  - Our recent study identified a list of differentially expressed microRNAs (miRNAs)
      in human prostate cancer (PCa) tissues compared to adjacent benign prostate
      tissues. In the current study, to identify the crucial miRNA-mRNA regulatory
      biomodule involved into prostate carcinogenesis based on the previous miRNA
      expression profile in PCa, we proposed an integrated systematic approach which
      combined miRNA-mediated gene expression regulatory network analysis, experimental
      validations in vitro and in vivo, as well as clinical significance evaluation. As
      a result, the CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I axis was identified as a
      bottleneck in the miRNA-mediated gene expression regulatory network of PCa
      according to network topological analysis. The direct binding relationship
      between TP73 and PCa downregulated miR-193a-5p, and the direct binding
      relationship between UBE2I and PCa upregulated miR-188-5p were both
      experimentally validated. In addition, miR-193a-5p had a more significant
      regulatory effect on the tumor promoter isoform of TP73-deltaNp73 than on the
      tumor suppressive isoform of TP73-TAp73. Importantly, the deregulation of either
      the miR-193a-5p-TP73 or miR-188-5p-UBE2I axes was significantly associated with
      aggressive progression and poor prognosis in PCa patients. Gain- and loss-of
      function experiments showed that miR-193a-5p efficiently inhibited in vitro PCa
      cell proliferation, migration, and invasion, and in vivo tumor growth, and
      markedly induced PCa cell apoptosis via regulating TP73 with a corresponding
      suppression of the CCND1-RNASEL-CDKN1A-MDM2 axis. In contrast, miR-188-5p exerted
      its tumor promoter roles through targeting UBE2I with a subsequent activation of
      the CCND1-RNASEL-CDKN1A-MDM2 axis. Taken together, this integrated analysis
      revealed the potential roles of the miR-193a-5p/TP73 and miR-188-5p/UBE2i
      negative regulation pairs in PCa. In addition to the significant clinical
      relevance, miR-193a-5p- and miR-188-5p-regulated CCND1-RNASEL-CDKN1A-TP73-MDM2
      UBE2I signaling may be a novel regulatory biomodule in prostate carcinogenesis.

PMID- 29467541
TI  - Inhibition of endo-lysosomal function exacerbates vascular calcification.
AB  - Vascular calcification is a pathologic response to mineral imbalances and is
      prevalent in atherosclerosis, diabetes mellitus, and chronic kidney disease. When
      located in the media, it is highly associated with increased cardiovascular
      morbidity and mortality, particularly in patients on dialysis. Vascular
      calcification is tightly regulated and controlled by a series of endogenous
      factors. In the present study, we assess the effects of lysosomal and endosomal
      inhibition on calcification in vascular smooth muscle cells (VSMCs) and aortic
      rings. We observed that lysosomal function was increased in VSMCs cultured in
      calcification medium containing 3.5 mM inorganic phosphate (Pi) and 3 mM calcium
      (Ca2+) for 7 days. We also found that the lysosomal marker lysosome-associated
      membrane protein 2 was markedly increased and colocalized with osteogenic markers
      in calcified aortas from vitamin D3-treated rats. Interestingly, both the
      lysosomal inhibitor chloroquine and the endosomal inhibitor dynasore dose
      dependently enhanced Pi + Ca2+-mediated VSMC calcification. Inhibition of
      lysosomal and endosomal function also promoted osteogenic transformation of
      VSMCs. Additionally, lysosome inhibition increased Pi-induced medial
      calcification of aortic rings ex vivo. These data suggest that the endosome
      lysosome system may play a protective role in VSMC and medial artery
      calcification.

PMID- 29467542
TI  - Tubulation repair mitigates misdirection of regenerating motor axons across a
      sciatic nerve gap in rats.
AB  - The repair of peripheral nerve laceration injury to obtain optimal function
      recovery remains a big challenge in the clinic. Misdirection of regenerating
      axons to inappropriate target, as a result of forced mismatch of endoneurial
      sheaths in the case of end-to-end nerve anastomosis or nerve autografting,
      represents one major drawback that limits nerve function recovery. Here we tested
      whether tubulation repair of a nerve defect could be beneficial in terms of nerve
      regeneration accuracy and nerve function. We employed sequential retrograde
      neuronal tracing to assess the accuracy of motor axon regeneration into the
      tibial nerve after sciatic nerve laceration and entubulation in adult Sprague
      Dawley rats. In a separate cohort of rats with the same sciatic nerve
      injury/repair protocols, we evaluated nerve function recovery behaviorally and
      electrophysiologically. The results showed that tubulation repair of the
      lacerated sciatic nerve using a 3-6-mm-long bioabsorbable guidance conduit
      significantly reduced the misdirection of motor axons into the tibial nerve as
      compared to nerve autografting. In addition, tubulation repair ameliorated
      chronic flexion contracture. This study suggests that tubulation repair of a
      nerve laceration injury by utilizing a bioresorbable nerve guidance conduit
      represents a potential substitute for end-to-end epineurial suturing and nerve
      autografting.

PMID- 29467543
TI  - AP-2epsilon Expression in Developing Retina: Contributing to the Molecular
      Diversity of Amacrine Cells.
AB  - AP-2 transcription factors play important roles in the regulation of gene
      expression during development. Four of the five members of the AP-2 family (AP
      2alpha, AP-2beta, AP-2gamma and AP-2delta) have previously been shown to be
      expressed in developing retina. Mouse knockouts have revealed roles for AP
      2alpha, AP-2beta and AP-2delta in retinal cell specification and function. Here,
      we show that the fifth member of the AP-2 family, AP-2epsilon, is also expressed
      in amacrine cells in developing mammalian and chicken retina. Our data indicate
      that there are considerably fewer AP-2epsilon-positive cells in the developing
      mouse retina compared to AP-2alpha, AP-2beta and AP-2gamma-positive cells,
      suggesting a specialized role for AP-2epsilon in a subset of amacrine cells. AP
      2epsilon, which is restricted to the GABAergic amacrine lineage, is most commonly
      co-expressed with AP-2alpha and AP-2beta, especially at early stages of retinal
      development. Co-expression of AP-2epsilon and AP-2gamma increases with
      differentiation. Analysis of previously published Drop-seq data from single
      retinal cells supports co-expression of multiple AP-2s in the same cell. Since AP
      2s bind to their target sequences as either homodimers or heterodimers, our work
      suggests spatially- and temporally-coordinated roles for combinations of AP-2
      transcription factors in amacrine cells during retinal development.

PMID- 29467544
TI  - Ultrasound detection of diaphragm position in the region for lung monitoring by
      electrical impedance tomography during laparoscopy.
AB  - BACKGROUND AND AIMS: During laparoscopic surgery, a capnoperitoneum is created to
      optimize the operating space for surgeons. One effect of this is abdominal
      pressure which alters the physiological thoraco-abdominal configuration and
      pushes the diaphragm and lungs cranially. Since the lung image acquired by
      electrical impedance tomography (EIT) depends on the conditions within the thorax
      and abdomen, it is crucial to know the diaphragm position to determine the effect
      of diaphragm shift on EIT thorax image. METHODS: The presence of diaphragm in the
      region of EIT measurement was determined by ultrasound in 20 patients undergoing
      laparoscopic surgery. Data were obtained in the supine position during
      spontaneous breathing in a mechanically ventilated patient under general
      anesthesia with muscle relaxation and in a mechanically ventilated patient under
      general anesthesia with muscle relaxation during capnoperitoneum. RESULTS: The
      diaphragm was shifted cranially during capnoperitoneum. The diaphragm detection
      rate rose by 10% during capnoperitoneum at the fifth intercostal space, from 55%
      to 65% and by 10% from 0% at mid-sternal level compared to mechanical ventilation
      without capnoperitoneum. CONCLUSION: The diaphragm was detected in the area
      contributing to the creation of the thoracic EIT image. Considering the cranial
      shift of diaphragm caused by excessive intra-abdominal pressure, the impedance
      changes in the abdomen and the principle of EIT, we assume there could be a
      significant impact on EIT image of the thorax acquired during capnoperitoneum.
      For this reason, for lung monitoring using EIT during capnoperitoneum, the
      manufacturer's recommendation for electrode belt position is not appropriate. The
      study was registered in ClinicalTrials.gov with an identifier NCT03038061.

PMID- 29467545
TI  - Vulnerable atherosclerotic plaque - a review of current concepts and advanced
      imaging.
AB  - Atherosclerosis is the most common cause of both carotid and coronary steno
      occlusive disease. Rupture of an atherosclerotic plaque may lead to the formation
      of an overlying thrombosis resulting in complete arterial occlusion or downstream
      embolism. Clinically, this may manifest as a stroke or acute myocardial
      infarction, the overall leading causes of mortality and disability in developed
      countries. In this article, we summarize current concepts of the development of
      vulnerable plaque and provide an overview of commonly used imaging methods that
      may suggest/indicate atherosclerotic plaque vulnerability.

PMID- 29467546
TI  - Chemiluminescent detection of oligoclonal immunoglobulins after isoelectric
      focusing and affinity-mediated immunoblotting.
AB  - BACKGROUND AND AIMS: Detection of oligoclonal IgG (o-IgG) in the cerebrospinal
      fluid (CSF) not found in serum is the principal laboratory test to support a
      diagnosis of multiple sclerosis. The aim of this study was to compare
      chemiluminescent and chromogenic detection of oligoclonal immunoglobulins in the
      cerebrospinal fluid and serum after their separation by means of isoelectric
      focusing followed by immunoblotting. METHODS: A set of experiments was designed
      to detect oligoclonal immunoglobulins by means of alkaline phosphatase BCIP/NBT
      substrate and chemiluminescent peroxidase substrate. RESULTS: Based on visual
      evaluation of signals, chemiluminescent detection requires about a 4 times lower
      amount of applied protein than very sensitive BCIP/NBT chromogenic detection.
      Very good correlation between methods has been shown for oligoclonal IgG. Antigen
      specific oligoclonal IgG could be demonstrated by both methods although the
      pattern was clearer using chemiluminescence. In one patient, oligoclonal IgD
      bands barely visible by BCIP/NBT were convincingly demonstrated by
      chemiluminescence. CONCLUSION: Chemiluminescent detection is a feasible option
      for oligoclonal immunoglobulin detection and could be used in cases when the
      sensitivity needs to be improved. Further studies and method optimisation are
      warranted.

PMID- 29467547
TI  - Prescriptive or Interpretive Regulation at the Frontlines of Care Work in the
      "Three Worlds" of Canada, Germany and Norway.
AB  - This paper examines the tension between macro level regulation and the rule
      breaking and rule following that happens at the workplace level. Using a
      comparative study of Canada, Norway, and Germany, the paper documents how long
      term residential care work is regulated and organized differently depending on
      country, regional, and organizational contexts. We ask where each jurisdiction's
      staffing regulations fall on a prescription-interpretation continuum; we define
      prescription as a regulatory tendency to identify what to do and when and how to
      do it, and interpretation as a tendency to delineate what to do but not when and
      how to do it. In examining frontline care workers' strategies for accomplishing
      everyday social, health, and dining care tasks we explore how a policy-level
      prescriptive or interpretive regulatory approach affects the potential for
      promising practices to emerge on the frontlines of care work. Overall, we note
      the following associations: prescriptive regulatory environments tend to be
      accompanied by a lower ratio of professional to non-professional staff, a higher
      concentration of for-profit providers, a lower ratio of staff to residents and a
      sharper division of labour. Interpretive regulatory environments tend to have
      higher numbers of professionals relative to non-professionals, more limited for
      profit provision, a higher ratio of staff to residents, and a more relational
      division of labour that enables the work to be more fluid and responsive. The
      implication of a prescriptive environment, such as is found in Ontario, Canada,
      is that frontline care workers possess less autonomy to be creative in meeting
      residents' needs, a tendency towards more task-oriented care and less job
      autonomy. The paper reveals that what matters is the type of regulation as well
      as the regulatory tendency towards controlling frontline care workers decision
      making and decision-latitude.

PMID- 29467548
TI  - Epidemiology, determinants, and management of AIDS cholangiopathy: A review.
AB  - Diseases of the liver and biliary tree have been described with significant
      frequency among patients with human immunodeficiency virus (HIV), and its
      advanced state, acquired immunodeficiency syndrome (AIDS). Through a variety of
      mechanisms, HIV/AIDS has been shown to affect the hepatic parenchyma and biliary
      tree, leading to liver inflammation and biliary strictures. One of the potential
      hepatobiliary complications of this viral infection is AIDS cholangiopathy, a
      syndrome of biliary obstruction and liver damage due to infection-related
      strictures of the biliary tract. AIDS cholangiopathy is highly associated with
      opportunistic infections and advanced immunosuppression in AIDS patients, and due
      to the increased availability of highly active antiretroviral therapy, is now
      primarily seen in instances of poor access to anti-retroviral therapy and
      medication non-compliance. While current published literature describes well the
      clinical, biochemical, and endoscopic management of AIDS-related cholangiopathy,
      information on its epidemiology, natural history, and pathology are not as well
      defined. The objective of this review is to summarize the available literature on
      AIDS cholangiopathy, emphasizing its epidemiology, course of disease, and
      determinants, while also revealing an updated approach for its evaluation and
      management.

PMID- 29467549
TI  - Glucose transporter expression in the human colon.
AB  - AIM: To investigate by immunostaining glucose transporter expression in human
      colorectal mucosa in controls and patients with inflammatory bowel disease (IBD).
      METHODS: Colorectal samples were obtained from patients undergoing lower
      endoscopic colonoscopy or recto-sigmoidoscopy. Patients diagnosed with ulcerative
      colitis (n = 18) or Crohn's disease (n = 10) and scheduled for diagnostic
      colonoscopy were enrolled. Patients who underwent colonoscopy for prevention
      screening of colorectal cancer or were followed-up after polypectomy or had a
      history of lower gastrointestinal symptoms were designated as the control group
      (CTRL, n = 16). Inflammatory status of the mucosa at the sampling site was
      evaluated histologically and/or endoscopically. A total of 147 biopsies of
      colorectal mucosa were collected and processed for immunohistochemistry analysis.
      The expression of GLUT2, SGLT1, and GLUT5 glucose transporters was investigated
      using immunoperoxidase labeling. To compare immunoreactivity of GLUT5 and LYVE-1,
      which is a marker for lymphatic vessel endothelium, double-labeled confocal
      microscopy was used. RESULTS: Immunohistochemical analysis revealed that GLUT2,
      SGLT1, and GLUT5 were expressed only in short epithelial portions of the large
      intestinal mucosa. No important differences were observed in glucose transporter
      expression between the samples obtained from the different portions of the
      colorectal tract and between the different patient groups. Unexpectedly, GLUT5
      expression was also identified in vessels, mainly concentrated in specific areas
      where the vessels were clustered. Immunostaining with LYVE-1 and GLUT5 antibodies
      revealed that GLUT5-immunoreactive (-IR) clusters of vessels were concentrated in
      areas internal to those that were LYVE-1 positive. GLUT5 and LYVE-1 did not
      appear to be colocalized but rather showed a close topographical relationship on
      the endothelium. Based on their LYVE-1 expression, GLUT5-IR vessels were
      identified as lymphatic. Both inflamed and non-inflamed mucosal colorectal tissue
      biopsies from the IBD and CTRL patients showed GLUT5-IR clusters of lymphatic
      vessels. CONCLUSION: Glucose transporter immunoreactivity is present in
      colorectal mucosa in controls and IBD patients. GLUT5 expression is also
      associated with lymphatic vessels. This novel finding aids in the
      characterization of lymphatic vasculature in IBD patients.

PMID- 29467550
TI  - Translational pancreatic cancer research: A comparative study on patient-derived
      xenograft models.
AB  - AIM: To assess the viability of orthotopic and heterotopic patient-derived
      pancreatic cancer xenografts implanted into nude mice. METHODS: This study
      presents a prospective experimental analytical follow-up of the development of
      tumours in mice upon implantation of human pancreatic adenocarcinoma samples.
      Specimens were obtained surgically from patients with a pathological diagnosis of
      pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were
      transplanted into nude mice in three different locations (intraperitoneal,
      subcutaneous and pancreatic). Histological analysis (haematoxylin-eosin and
      Masson's trichrome staining) and immunohistochemical assessment of apoptosis
      (TUNEL), proliferation (Ki-67), angiogenesis (CD31) and fibrogenesis (alpha-SMA)
      were performed. When a tumour xenograft reached the target size, it was re
      implanted in a new nude mouse. Three sequential tumour xenograft generations were
      generated (F1, F2 and F3). RESULTS: The overall tumour engraftment rate was
      61.1%. The subcutaneous model was most effective in terms of tissue growth
      (69.9%), followed by intraperitoneal (57.6%) and pancreatic (55%) models. Tumour
      development was faster in the subcutaneous model (17.7 +/- 2.6 wk) compared with
      the pancreatic (23.1 +/- 2.3 wk) and intraperitoneal (25.0 +/- 2.7 wk) models (P
      = 0.064). There was a progressive increase in the tumour engraftment rate over
      successive generations for all three models (F1 28.1% vs F2 71.4% vs F3 80.9%, P
      < 0.001). There were no significant differences in tumour xenograft
      differentiation and cell proliferation between human samples and the three
      experimental models among the sequential generations of tumour xenografts.
      However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation
      and apoptosis was observed in the three experimental models compared with the
      human samples. All three pancreatic patient-derived xenograft models presented
      similar histological and immunohistochemical characteristics. CONCLUSION: In our
      experience, the faster development and greatest number of viable xenografts could
      make the subcutaneous model the best option for experimentation in pancreatic
      cancer.

PMID- 29467551
TI  - Cryopreservation for delayed circulating tumor cell isolation is a valid strategy
      for prognostic association of circulating tumor cells in gastroesophageal cancer.
AB  - AIM: To demonstrate the feasibility of cryopreservation of peripheral blood
      mononuclear cells (PBMCs) for prognostic circulating tumor cell (CTC) detection
      in gastroesophageal cancer. METHODS: Using 7.5 mL blood samples collected in EDTA
      tubes from patients with gastroesopheagal adenocarcinoma, CTCs were isolated by
      epithelial cell adhesion molecule based immunomagnetic capture using the IsoFlux
      platform. Paired specimens taken during the same blood draw (n = 15) were used to
      compare number of CTCs isolated from fresh and cryopreserved PBMCs. Blood samples
      were processed within 24 h to recover the PBMC fraction, with PBMCs used for
      fresh analysis immediately processed for CTC isolation. Cryopreservation of PBMCs
      lasted from 2 wk to 25.2 mo (median 14.6 mo). CTCs isolated from pre-treatment
      cryopreserved PBMCs (n = 43) were examined for associations with
      clinicopathological variables and survival outcomes. RESULTS: While there was a
      significant trend to a decrease in CTC numbers associated with cryopreserved
      specimens (mean number of CTCs 34.4 vs 51.5, P = 0.04), this was predominately in
      samples with a total CTC count of > 50, with low CTC count samples less affected
      (P = 0.06). There was no significant association between the duration of
      cryopreservation and number of CTCs. In cryopreserved PBMCs from patient samples
      prior to treatment, a high CTC count (> 17) was associated with poorer overall
      survival (OS) (n = 43, HR = 4.4, 95%CI: 1.7-11.7, P = 0.0013). In multivariate
      analysis, after controlling for sex, age, stage, ECOG performance status, and
      primary tumor location, a high CTC count remained significantly associated with a
      poorer OS (HR = 3.7, 95%CI: 1.2-12.4, P = 0.03). CONCLUSION: PBMC
      cryopreservation for delayed CTC isolation is a valid strategy to assist with
      sample collection, transporting and processing.

PMID- 29467552
TI  - Metformin attenuates motility, contraction, and fibrogenic response of hepatic
      stellate cells in vivo and in vitro by activating AMP-activated protein kinase.
AB  - AIM: To investigate the effect of metformin on activated hepatic stellate cells
      (HSCs) and the possible signaling pathways involved. METHODS: A fibrotic mouse
      model was generated by intraperitoneal injection of carbon tetrachloride (CCl4)
      and subsequent treatment with or without metformin. The level of fibrosis was
      detected by hematoxylin-eosin staining, Sirius Red staining, and
      immunohistochemistry. The HSC cell line LX-2 was used for in vitro studies. The
      effect of metformin on cell proliferation (CCK8 assay), motility (scratch test
      and Transwell assay), contraction (collagen gel contraction assay), extracellular
      matrix (ECM) secretion (Western blot), and angiogenesis (ELISA and tube formation
      assay) was investigated. We also analyzed the possible signaling pathways
      involved by Western blot analysis. RESULTS: Mice developed marked liver fibrosis
      after intraperitoneal injection with CCl4 for 6 wk. Metformin decreased the
      activation of HSCs, reduced the deposition of ECM, and inhibited angiogenesis in
      CCl4-treated mice. Platelet-derived growth factor (PDGF) promoted the fibrogenic
      response of HSCs in vitro, while metformin inhibited the activation,
      proliferation, migration, and contraction of HSCs, and reduced the secretion of
      ECM. Metformin decreased the expression of vascular endothelial growth factor
      (VEGF) in HSCs through inhibition of hypoxia inducible factor (HIF)-1alpha in
      both PDGF-BB treatment and hypoxic conditions, and it down-regulated VEGF
      secretion by HSCs and inhibited HSC-based angiogenesis in hypoxic conditions in
      vitro. The inhibitory effects of metformin on activated HSCs were mediated by
      inhibiting the Akt/mammalian target of rapamycin (mTOR) and extracellular signal
      regulated kinase (ERK) pathways via the activation of adenosine monophosphate
      activated protein kinase (AMPK). CONCLUSION: Metformin attenuates the fibrogenic
      response of HSCs in vivo and in vitro, and may therefore be useful for the
      treatment of chronic liver diseases.

PMID- 29467553
TI  - Fish oil alleviates liver injury induced by intestinal ischemia/reperfusion via
      AMPK/SIRT-1/autophagy pathway.
AB  - AIM: To evaluate whether fish oil (FO) can protect liver injury induced by
      intestinal ischemia/reperfusion (I/R) via the AMPK/SIRT-1/autophagy pathway.
      METHODS: Ischemia in Wistar rats was induced by superior mesenteric artery
      occlusion for 60 min and reperfusion for 240 min. One milliliter per day of FO
      emulsion or normal saline was administered by intraperitoneal injection for 5
      consecutive days to each animal. Animals were sacrificed at the end of
      reperfusion. Blood and tissue samples were collected for analyses. AMPK, SIRT-1,
      and Beclin-1 expression was determined in lipopolysaccharide (LPS)-stimulated
      HepG2 cells with or without FO emulsion treatment. RESULTS: Intestinal I/R
      induced significant liver morphological changes and increased serum alanine
      aminotransferase and aspartate aminotransferase levels. Expression of p
      AMPK/AMPK, SIRT-1, and autophagy markers was decreased whereas tumor necrosis
      factor-alpha (TNF-alpha) and malonaldehyde (MDA) were increased. FO emulsion
      blocked the changes of the above indicators effectively. Besides, in LPS
      stimulated HepG2 cells, small interfering RNA (siRNA) targeting AMPK impaired the
      FO induced increase of p-AMPK, SIRT-1, and Beclin-1 and decrease of TNF-alpha and
      MDA. SIRT-1 siRNA impaired the increase of SIRT-1 and Beclin-1 and the decrease
      of TNF-alpha and MDA. CONCLUSION: Our study indicates that FO may protect the
      liver against intestinal I/R induced injury through the AMPK/SIRT-1/autophagy
      pathway.

PMID- 29467554
TI  - Elderly patients had more severe postoperative complications after pancreatic
      resection: A retrospective analysis of 727 patients.
AB  - AIM: To examine the impact of aging on the short-term outcomes following
      pancreatic resection (PR) in elderly patients. METHODS: A retrospective cohort
      study using prospectively collected data was conducted at the China National
      Cancer Center. Consecutive patients who underwent PR from January 2004 to
      December 2015 were identified and included. 'Elderly patient' was defined as ones
      age 65 and above. Comorbidities, clinicopathology, perioperative variables, and
      postoperative morbidity and mortality were compared between the elderly and young
      patients. Univariate and multivariate analyses were performed using the Cox
      proportional hazard model for severe postoperative complications (grades IIIb-V).
      RESULTS: A total of 454 (63.4%) patients were < 65-years-old and 273 (36.6%)
      patients were >= 65-years-old, respectively. Compared to patients < 65-years-old,
      elderly patients had worse American Society of Anesthesiologists scores (P =
      0.007) and more comorbidities (62.6% vs 32.4%, P < 0.001). Elderly patients had
      more severe postoperative complications (16.8% vs 9.0%, P = 0.002) and higher
      postoperative mortality rates (5.5% vs 0.9%, P < 0.001). In the multivariate Cox
      proportional hazards model for severe postoperative complications, age >= 65
      years [hazard ratio (HR) = 1.63; 95% confidence interval (CI): 1.18-6.30], body
      mass index >= 24 kg/m2 (HR = 1.20, 95%CI: 1.07-5.89), pancreaticoduodenectomy (HR
      = 4.86, 95%CI: 1.20-8.31) and length of operation >= 241 min (HR = 2.97; 95%CI:
      1.04-6.14) were significant (P = 0.010, P = 0.041, P = 0.017 and P = 0.012,
      respectively). CONCLUSION: We found that aging is an independent risk factor for
      severe postoperative complications after PR. Our results might contribute to more
      informed decision-making for elderly patients.

PMID- 29467555
TI  - Predictors of functional benefit of hepatitis C therapy in a 'real-life' cohort.
AB  - AIM: To define predictors of functional benefit of direct-acting antivirals
      (DAAs) in patients with chronic hepatitis C virus (HCV) infection and liver
      cirrhosis. METHODS: We analysed a cohort of 199 patients with chronic HCV
      genotype 1, 2, 3 and 4 infection involving previously treated and untreated
      patients with compensated (76%) and decompensated (24%) liver cirrhosis at two
      tertiary centres in Germany. Patients were included with treatment initiation
      between February 2014 and August 2016. All patients received a combination
      regimen of one or more DAAs for either 12 or 24 wk. Predictors of functional
      benefit were assessed in a univariable as well as multivariable model by binary
      logistic regression analysis. RESULTS: Viral clearance was achieved in 88%
      (175/199) of patients. Sustained virological response (SVR) 12 rates were as
      follows: among 156 patients with genotype 1 infection the SVR 12 rate was 90% (n
      = 141); among 7 patients with genotype 2 infection the SVR 12 rate was 57% (n =
      4); among 30 patients with genotype 3 infection the SVR 12 rate was 87% (n = 26);
      and among 6 patients with genotype 4 infection the SVR 12 rate was 67% (n = 4).
      Follow-up MELD scores were available for 179 patients. A MELD score improvement
      was observed in 37% (65/179) of patients, no change of MELD score in 41% (74/179)
      of patients, and an aggravation was observed in 22% (40/179) of patients. We
      analysed predictors of functional benefit from antiviral therapy in our patients
      beyond viral eradication. We identified the Child-Pugh score, the MELD score, the
      number of platelets and the levels of albumin and bilirubin as significant
      factors for functional benefit. CONCLUSION: Our data may contribute to the
      discussion of potential risks and benefits of antiviral therapy with individual
      patients infected with HCV and with advanced liver disease.

PMID- 29467556
TI  - Predictors of post-treatment stenosis in cervical esophageal cancer undergoing
      high-dose radiotherapy.
AB  - AIM: To evaluate toxicity and treatment outcome of high-dose radiotherapy (RT)
      for cervical esophageal cancer (CEC). METHODS: We reviewed a total of 62
      consecutive patients who received definitive RT for stage I to III cervical
      esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated
      for lesions below sternal notch, treated with palliative aim, treated with
      subsequent surgical resection, or diagnosed with synchronous hypopharyngeal
      cancer were excluded. Treatment failures were divided into local (occurring
      within the RT field), outfield-esophageal, and regional [occurring in regional
      lymph node(s)] failures. Factors predictive of esophageal stenosis requiring
      endoscopic dilation were analyzed. RESULTS: Grade 1, 2, and 3 esophagitis
      occurred in 19 (30.6%), 39 (62.9%), and 4 patients (6.5%), respectively, without
      grade >= 4 toxicities. Sixteen patients (25.8%) developed post-RT stenosis, of
      which 7 cases (43.8%) were malignant. Four patients (6.5%) developed
      tracheoesophageal fistula (TEF), of which 3 (75%) cases were malignant. Factors
      significantly correlated with post-RT stenosis were stage T3/4 (P = 0.001),
      complete circumference involvement (P < 0.0001), stenosis at diagnosis (P =
      0.024), and endoscopic complete response (P = 0.017) in univariate analysis,
      while complete circumference involvement was significant in multivariate analysis
      (P = 0.003). A higher dose (>= 60 Gy) was not associated with occurrence of post
      RT stenosis or TEF. With a median follow-up of 24.3 (range, 3.4-152) mo, the 2 y
      local control, outfield esophageal control, progression-free survival, and
      overall survival (OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively.
      Factors significantly correlated with OS were complete circumference involvement
      (P = 0.023), stenosis at diagnosis (P < 0.0001), and occurrence of post-RT
      stenosis or TEF (P < 0.001) in univariate analysis, while stenosis at diagnosis
      (P = 0.004) and occurrence of post-RT stenosis or TEF (P = 0.023) were
      significant in multivariate analysis. CONCLUSION: Chemoradiation for CEC was well
      tolerated, and a higher dose was not associated with stenosis. Patients with
      complete circumferential involvement require close follow-up.

PMID- 29467557
TI  - Esophageal metastasis of stem cell-subtype hepatocholangiocarcinoma: Rare
      presentation of a rare tumor.
AB  - Hepatocholangiocarcinoma (cHCC-ICC) is a rare primary hepatic tumor defined by
      the presence of histological features of both hepatocellular carcinoma (HCC) and
      intrahepatic cholangiocarcinoma (ICC). Its prevalence ranges from 1%-5% of all
      primary liver cancers. We report the case of a 55-year-old cirrhotic male patient
      admitted to our university hospital for dysphagia, revealing a 10 cm lower-third
      esophageal metastasis of an unresectable cHCC-ICC with stem-cell features.
      Computed tomography and abdominal magnetic resonance imaging scans revealed
      multiple hepatic lesions combining features of both HCC and ICC, associated with
      synchronous bone metastasis. Histological and immunohistochemical analyses of
      biopsies from the esophageal lesion and the hepatic tumor confirmed the diagnosis
      of cHCC-ICC with a stem cell-subtype, according to the World Health Organization
      classification. After a multidisciplinary meeting, the patient was treated with
      chemotherapy. He received two cycles of a gemcitabine plus cisplatin regimen
      before bone progression, and he died 3 mo after the initial diagnosis.

PMID- 29467558
TI  - Correction for "Evaluation of a multiplex PCR assay for detection of
      cytomegalovirus in stool samples from patients with ulcerative colitis" (World J
      Gastroenterol 2015; 21: 12667-12675).
AB  - [This corrects the article on p. 12667 in vol. 21, PMID: 26640344.].

PMID- 29467559
TI  - Perspective: Person-Environment Congruence: A Call for Increased Precision in
      Matching Research Mentors and Mentees.

PMID- 29467560
TI  - Implementation of The Steps Toward Academic Research (STAR) Fellowship Program to
      Promote Underrepresented Minority Faculty into Health Disparity Research.
AB  - Eliminating disparities in health can benefit from the inclusion of diverse
      populations pursuing health disparity research careers. A goal of the Texas
      Center for Health Disparities (TCHD) is to provide opportunities for
      underrepresented minority faculty to become successful health disparity
      researchers. The TCHD created the Steps Toward Academic Research (STAR)
      fellowship program to provide faculty and community partners a yearlong face-to
      face and online hybrid curriculum focused on acquiring fundamental concepts in
      biomedical and behavioral health disparity research, basics in grantsmanship as
      well as professional development skills. In total, this training approach is
      envisioned to provide mutually beneficial co-learning experiences that will
      increase the number of under-represented minorities (URMs) entering translational
      research focused on the elimination of health disparities.

PMID- 29467561
TI  - Development of a Participatory Capacity-Building Program for Congregational
      Health Leaders in African American Churches in the US South.
AB  - African Americans are disproportionately affected by diabetes and colorectal
      cancer. Although studies have shown the effectiveness of spiritually based health
      interventions delivered by community health workers to African Americans, few
      have described the development of the capacity-building component. This article
      describes this process. The development of the Healthy Congregations Healthy
      Communities Program (HCHC) was guided through a community-based participatory
      research lens and included: 1) establishment of a community coalition; 2)
      identification by coalition members of churches as the best venues for health
      promotion strategies among African Americans; 3) recruitment of churches; 4)
      development of a training manual; 5) recruitment and training of congregational
      health leaders (CHLs); and 6) "Passing of the torch" from the coalition to the
      CHLs who implemented the intervention in their congregations. We trained 35 CHLs
      to promote awareness about diabetes and colorectal cancer using a culturally
      relevant, spiritually based curriculum. Pre- and post-test paired t-tests showed
      significant increases in CHLs' knowledge of wellness (P<.001), colorectal cancer
      (P<.002), nutrition (P<.004), and lifestyle changes (P<.005). The community
      academic partnership was successful in developing a culturally relevant,
      spiritually based capacity-building program for African American CHLs to
      implement health promotion strategies in their congregations and communities.

PMID- 29467562
TI  - Fasting Plasma Glucose and the HbA1c Are Not Optimal Screening Modalities for the
      Diagnosis of New Diabetes in Previously Undiagnosed Asian Indian Community
      Participants.
AB  - Objectives: There is no definitive consensus on the screening algorithm in high
      risk communities for diabetes. The aims of our study were to determine the
      prevalence of undiagnosed diabetes in a high-risk community using the oral
      glucose tolerance test (OGTT), as well as determine the value of anthropometric
      measurements and other measures of glycemia in the detection of diabetes. Method:
      All participants from the Phoenix Lifestyle project without known diabetes, and
      who had undergone an OGTT were selected for study. Anthropometric measurements
      were collected according to accepted guidelines. Diabetes was diagnosed if
      fasting plasma glucose (FPG) >=7.0 mmol/l, if 2-hour plasma glucose level during
      OGTT was >= 11.0 mmol/l, or if HbA1c >= 6.5%. Results: The prevalence of newly
      diagnosed diabetes was 14.3% (11.7 % age standardized) (women=15.4%; men=11.8%).
      The prevalence rates were underestimated using FPG criteria, but overestimated
      when using the HbA1c. The AUC (area under the receiver-operator characteristics
      curve) was highest for FPG (.879), HbA1c (.855), then anthropometry measures
      (BMI=.621; waist circumference=.627). For diabetes, at levels >6.3, the
      discriminant ability (DA) of HbA1c was highest (79%), while a cut-point of
      >=5.5mmol/l for FPG yielded a DA= 81.5% (82% sensitivity; 81%; specificity of
      81%). There was a low level of agreement between the FPG (Kappa = .506), HbA1c
      (Kappa = .537), and the OGTT. Age- and sex-adjusted independent determinants of
      diabetes using stepwise backward logistic regression were age, triglyceride
      levels and a positive family history for diabetes. Conclusion: Neither the HbA1c
      nor the FPG approached adequate predictive accuracy in the diagnosis of diabetes.
      In view of the high prevalence of undiagnosed diabetes, this study underscores
      the need for ongoing national surveillance data.

PMID- 29467563
TI  - Sociocultural Influences on African Americans' Representations of Type 2
      Diabetes: A Qualitative Study.
AB  - Objective: Illness representations, known as patients' beliefs and expectations
      about an illness, may be influenced by cultural beliefs and personal experiences.
      This study explored African Americans' perceptions of the sociocultural factors
      that influence their representations of diabetes. Design: Six semi-structured
      focus groups. Setting: Private space at a convenient site. Participants: Forty
      African Americans, aged 45-60 years with type 2 diabetes for at least one year
      prior. Results: Participants perceived that there was a race-mediated effect of
      how they developed diabetes because of poverty due to past slavery, racial
      discrimination by health care providers, and the stigma associated with diabetes
      within the African American community. Participants perceived that poverty
      influenced African Americans' unhealthy eating habits, which led to diabetes
      diagnosis among their ancestors and their development of the disease since it was
      hereditary. Participants also perceived that there was provider ill intention,
      ie, providers were purposefully making people sick, and their lack of education
      on diabetes from providers was done on purpose, as information on diabetes was
      withheld and not shared due to racial discrimination. Perceived stigma by the
      community led to African Americans' avoidance and denial of the disease, and
      subsequently the development of diabetes. Conclusions: To enhance disease
      management for African Americans with diabetes, it is important to focus on the
      sociocultural context of how African Americans view their world that may be
      influenced by their knowledge of negative historical circumstances and their
      current provider relationship, which, in turn, may be reflected in their
      perceptions of diabetes.

PMID- 29467564
TI  - Determinants of Obesity in Two Urban Communities: Perceptions and Community
      Driven Solutions.
AB  - Objective: In the search of solutions to the rising rates of obesity, community
      perspectives are important because they highlight areas of need and help
      determine the level of community support for potential interventions. This study
      aimed to identify community perceptions of factors associated with obesity in two
      urban municipalities - one racially mixed and one predominantly African American 
      and to explore community-driven solutions to the problem of obesity. Methods:
      The study used Photovoice methodology to understand what community members
      perceived as obesity-promoting factors in their residential environments.
      Results: A total of 96 photographs of factors relevant to obesity were discussed.
      Most commonly depicted were restaurants, grocery stores, fast food, and fitness
      centers. In 10 race-stratified focus groups, participants made 592 comments on 12
      themes, the most common being restaurants, physical activity, food stores, and
      proposed solutions. The top three themes - restaurants, physical activity, and
      food stores - accounted for 58% of all barriers to healthy weight. Proposed
      solutions ranged from personal efforts and peer support, to educating adults and
      children, to community action. Conclusions: Interventions addressing the
      immediate food and physical activity environment - restaurants, grocery stores,
      and resources for physical activity - may have high likelihood of success as they
      align with community needs and understanding of priorities. Health education and
      promotion programs that increase food-related knowledge and skills are also
      needed and likely to receive strong community support.

PMID- 29467565
TI  - Racial Differences in Weight Loss Mediated by Engagement and Behavior Change.
AB  - Objective: We set out to determine if a primarily Internet-delivered behavioral
      weight loss intervention produced differential weight loss in African American
      and non-Hispanic White women, and to identify possible mediators. Design: Data
      for this analysis were from a randomized controlled trial, collected at baseline
      and 4-months. Setting: The intervention included monthly face-to-face group
      sessions and an Internet component that participants were recommended to use at
      least once weekly. Participants: We included overweight or obese African American
      and non-Hispanic White women (n=170), with at least weekly Internet access, who
      were able to attend group sessions. Intervention: Monthly face-to-face group
      sessions were delivered in large or small groups. The Internet component included
      automated tailored feedback, self-monitoring tools, written lessons, video
      resources, problem solving, exercise action planning tools, and social support
      through message boards. Main Outcome Measure: Multiple linear regression was used
      to evaluate race group differences in weight change. Results: Non-Hispanic White
      women lost more weight than African American women (-5.03% vs.-2.39%, P=.0002).
      Greater website log-ins and higher change in Eating Behavior Inventory score in
      non-Hispanic White women partially mediated the race-weight loss relationship.
      Conclusions: The weight loss disparity may be addressed through improved website
      engagement and adoption of weight control behaviors.

PMID- 29467566
TI  - Prevalence of Self-Reported Chronic Diseases and Health Services Utilization by
      Ethnic Minorities in Manaus Metropolitan Region.
AB  - Objectives: To assess the prevalence of, and associated factors to, self-reported
      chronic diseases and health care utilization by ethnicity in the Manaus
      Metropolitan Region. Methods: We conducted a cross-sectional, population-based
      survey from May through August 2015. Using probabilistic sampling in three
      stages, we recruited adults aged >=18 years. Ethnicity was self-identified as
      White, Black, Yellow, Brown (Brazilian mixed-race), and Indigenous. We calculated
      adjusted prevalence ratios (PR) and 95% CI of chronic diseases and health service
      utilization for each ethnic minority and compared the data using Poisson
      regression with data from White respondents. Results: In this study, we
      interviewed 4,001 people. Of these, 15.9% were White, 7.5% Black, 3.4% Yellow,
      72.1% Brown, and 1.0% Indigenous. Indigenous respondents had the highest
      prevalence of self-reported hypertension (29.4%), diabetes (12.3%) and
      hypercholesterolemia (17.0%) among the ethnic respondent groups. Compared with
      the White population, Browns had less health insurance coverage (PR=.76; 95% CI:
      .62-.93) and reported hypertension (PR=.84; 95% CI: .72-0.98) and diabetes
      (PR=.69; 95% CI: .51-.94) less frequently. Yellows visited the doctor more
      frequently than Whites (PR=1.13; 95% CI: 1.04-1.22), with no significant
      difference in prevalence of diseases. Conclusions: Indigenous respondents had
      higher prevalence rates of the investigated diseases. Compared with Whites, Brown
      respondents had lower rates of self-reported arterial hypertension and diabetes,
      as well as lower rates of private health insurance coverage.

PMID- 29467567
TI  - Acculturation, Mental Health, and Quality of Life among Hispanic Childhood Cancer
      Survivors: A Latent Class Analysis.
AB  - Objective: Acculturation appears to be an important aspect of the association
      between ethnicity and disease, but it has not been explored in depth among
      childhood cancer survivors (CCS). The purpose of our study was to identify
      distinct acculturative profiles among Hispanic CCS and to assess differences in
      quality of life and depressive symptoms. Design: Latent class analysis was used
      to identify distinct acculturative profiles using 9 indicator items reflecting
      Hispanic and Anglo cultural orientation. Multinomial logistic regression was
      performed to explore differences in depressive symptoms and quality of life
      between acculturation classes. Setting and Participants: Participants were
      diagnosed in Los Angeles County, California, USA between 2000-2007 and were
      recruited for the study in 2009. Main Outcome Measures: Center for Epidemiologic
      Studies depression scale and the PedsQL 4.0 quality of life scale. Results: Three
      distinct acculturation classes emerged. All classes displayed a high probability
      of endorsing all Anglo orientation items. One class additionally demonstrated a
      high probability of endorsing all Hispanic orientation items and was labeled
      bicultural 40%); another demonstrated low probability of endorsing the Hispanic
      items so was labeled assimilated (32%); and the last demonstrated a high
      probability of endorsing only the Hispanic items related to language use and was
      labeled linguistically Hispanic/culturally Anglo (LH) (28%). Conclusions: The
      assimilated group had significantly more depressive symptoms and lower quality of
      life than the other two groups. This may indicate that loss of the Hispanic
      culture may be associated with poorer psychosocial health among CCS.

PMID- 29467568
TI  - Commentary: Addressing Racial Disparities in Stroke: The Wide Spectrum
      Investigation of Stroke Outcome Disparities on Multiple Levels (WISSDOM).
AB  - Racial-ethnic disparities in stroke recovery are well-established in the United
      States but the underlying causes are not well-understood. The typical assumption
      that racial-ethnic disparities in stroke recovery are explained by health care
      access inequities may be simplistic as access to stroke-related rehabilitation,
      for example, does not adequately explain the observed disparities. To approach
      the problem in a more comprehensive fashion, the Wide Spectrum Investigation of
      Stroke Outcome Disparities on Multiple Levels (WISSDOM) was developed to bring
      together scientists from Regenerative Medicine, Neurology, Rehabilitation, and
      Nursing to examine disparities in stroke "recovery." As a result, three related
      projects (basic science, clinical science and population science) were designed
      utilizing animal modeling, mapping of brain connections, and community-based
      interventions. In this article we describe: 1) the goals and objectives of the
      individual projects; and 2) how these projects could provide critical evidence to
      explain why racial-ethnic minorities traditionally experience recovery
      trajectories that are worse than Whites.

PMID- 29467569
TI  - Ten Basic Rules of Antibody Validation.
AB  - The quality of research antibodies is an issue for decades. Although several
      papers have been published to improve the situation, their impact seems to be
      limited. This publication makes the effort to simplify the description of
      validation criteria in a way that the occasional antibody user is able to assess
      the validation level of an immunochemical reagent. A simple, 1-page checklist is
      supplied for the practical application of these criteria.

PMID- 29467570
TI  - Reference ranges for antiepileptic drugs revisited: a practical approach to
      establish national guidelines.
AB  - Background and objective: Laboratories sometimes use different reference ranges
      for the same antiepileptic drug (AED), particularly for new and poorly
      investigated drugs. This may contribute to misunderstandings, concerns or
      inappropriate dose changes, which in turn may affect therapeutic effect, drug
      safety or treatment adherence. Therefore, the Norwegian Association of Clinical
      Pharmacology wished to update and harmonize the reference ranges for AEDs and
      establish national guidelines for Norway. Methods: A working group collected
      information on the reference ranges used by Norwegian laboratories for all
      commonly used AEDs. These reference ranges were compared to recent
      recommendations by the International League Against Epilepsy, current literature,
      applicable clinical studies, reference ranges used by leading Northern European
      epilepsy centers outside of Norway, and routine data derived from Norwegian
      laboratory databases. Results: Reference ranges varied between laboratories for
      four of 23 available AEDs (lamotrigine, valproate, eslicarbazepine and
      oxcarbazepine). For four AEDs (brivaracetam, perampanel, stiripentol and
      sulthiame), reference ranges had not previously been established. In total, 13
      reference ranges were either harmonized, updated or newly established. No changes
      were applied to the remaining 10 AEDs. Conclusion: Updated and harmonized
      reference ranges are now available for 22 of the 23 AEDs available in Norway. The
      exception is vigabatrin (reference range not applicable). Revision of reference
      ranges is an important part of pharmacovigilance of AEDs and must be a continuous
      process based on current literature and clinical experience.

PMID- 29467571
TI  - Vitrectomy in patients 85 years of age and older: surgical outcomes and visual
      prognosis.
AB  - Purpose: To evaluate visual and surgical outcomes in very elderly patients (above
      85 years of age) undergoing pars plana vitrectomy (PPV). Patients and methods: A
      single-center, retrospective study was carried out on the medical records of 82
      patients aged 85 years and older who had undergone PPV from 2006 to 2013.
      Patients ranged in age from 86 to 99 years, with a mean age of 88.9 years (+/
      2.88). Visual results and intraoperative and postoperative complications were the
      main outcome measures. Visual improvement/worsening was defined as at least +/
      0.1 logMAR change. Results: Mean follow-up was 7.25 months (+/-5.35), with a
      range of 1-28 months. General anesthesia was used in 63% of the operations. The
      most common indication was retinal detachment (27%). The ocular condition
      necessitating PPV was secondary to trauma (most commonly after a fall) in 10 eyes
      (12%). Mean visual acuity (VA) improved from 1/58 preoperatively to 1/29 at the
      final evaluation (p=0.014). Mean improvement in VA in eyes of patients with the
      comorbidity of age-related macular degeneration (n=34) was 41% lower compared to
      eyes of patients without the disease (n=48, p=0.013). In the subgroup of patients
      operated on for retinal detachment, 45.4% did not reach primary anatomic success
      and 45.4% needed additional retina-affecting surgery. One or more major ocular
      complications were reported in 24 eyes (29%), while 19 eyes (23%) had minor
      ocular complications. Conclusion: Improved VA was documented in more than half of
      the older adults aged 85-99 undergoing vitrectomy. Despite the rate of
      complications in the very elderly, the possibility of optimizing visual function
      may positively affect quality of life in this subgroup.

PMID- 29467572
TI  - Prevalence of geriatric syndromes among people aged 65 years and older at four
      community clinics in Moscow.
AB  - Background: Geriatric syndromes (GSs) are common in older adults and have a
      significant effect on their quality of life, disability, and use of health care
      resources. Few studies have assessed the prevalence of GSs in Russia. The aim of
      this study is to assess the prevalence of GSs among older adults living in the
      community in Moscow. Methods: A cross-sectional study was conducted in four
      community clinics in Moscow. A total of 1,220 patients completed a screening
      questionnaire, and 356 of them also underwent a comprehensive geriatric
      assessment (CGA). Results: The mean age of the 1,220 participants was 74.9+/-6.1
      years; 75.5% were women. Based on the questionnaire, 58.3% reported visual or
      hearing impairment, 58.2% cognitive impairment, 46% mood disorder, 42% difficulty
      walking, 28.3% urinary incontinence, 21.3% traumatic falls (over the previous
      year), and 12.2% weight loss. The mean number of GSs per patient was 2.9+/-1.5.
      Based on CGA, a decline in Instrumental Activity of Daily Living score was
      identified in 34.8% of the patients, a risk of malnutrition (Mini-Nutritional
      Assessment score, 17-23.5) in 25.8%, probable cognitive impairment (Mini-Mental
      State Examination score <25) in 8.6%, and symptoms of depression (15-item
      Geriatric Depression Scale score >5) in 36.2%. On the whole, patients
      demonstrated good mobility (average walking speed, 1+/-0.2 m/s) and hand grip
      strength (23.9+/-6.4 kg in women and 39.1+/-8.3 kg in men), but poor balance
      (only 39.4% were able to maintain their balance on one leg for 10 s or more).
      Conclusion: The results of this study demonstrate a high prevalence of GSs among
      community-dwelling people aged 65 years and older in Moscow. The results provide
      a better understanding of the needs of older adults in Russia and can facilitate
      planning for medical and social assistance for this population.

PMID- 29467573
TI  - Increased skin permeation efficiency of imperatorin via charged ultradeformable
      lipid vesicles for transdermal delivery.
AB  - Aim: The aim of this work was to develop a novel vesicular carrier,
      ultradeformable liposomes (UDLs), to expand the applications of the Chinese
      herbal medicine, imperatorin (IMP), and increase its transdermal delivery.
      Methods: In this study, we prepared IMP-loaded UDLs using the thin-film hydration
      method and evaluated their encapsulation efficiency, vesicle deformability, skin
      permeation, and the amounts accumulated in different depths of the skin in vitro.
      The influence of different charged surfactants on the properties of the UDLs was
      also investigated. Results: The results showed that the UDLs containing cationic
      surfactants had high entrapment efficiency (60.32%+/-2.82%), an acceptable
      particle size (82.4+/-0.65 nm), high elasticity, and prolonged drug release. The
      penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP
      suspension, which was the highest value among the vesicular carriers. UDLs
      modified with cationic surfactant also showed higher fluorescence intensity in
      deeper regions of the epidermis. Conclusion: The results of our study suggest
      that cationic surfactant-modified UDLs could increase the transdermal flux,
      prolong the release of the drug, and serve as an effective dermal delivery system
      for IMP.

PMID- 29467574
TI  - A hydrogel biosensor for high selective and sensitive detection of amyloid-beta
      oligomers.
AB  - Background: Alzheimer's disease (AD) is a neurodegenerative disorder
      characterized by progressive cognitive and memory impairment. It is the most
      common neurological disease that causes dementia. Soluble amyloid-beta oligomers
      (AbetaO) in blood or cerebrospinal fluid (CSF) are the pathogenic biomarker
      correlated with AD. Methods: A simple electrochemical biosensor using graphene
      oxide/gold nanoparticles (GNPs) hydrogel electrode was developed in this study.
      Thiolated cellular prion protein (PrPC) peptide probe was immobilized on GNPs of
      the hydrogel electrode to construct an AbetaO biosensor. Electrochemical
      impedance spectroscopy was utilized for AbetaO analysis. Results: The specific
      binding between AbetaO and PrPC probes on the hydrogel electrode resulted in an
      increase in the electron-transfer resistance. The biosensor showed high
      specificity and sensitivity for AbetaO detection. It could selectively
      differentiate AbetaO from amyloid-beta (Abeta) monomers or fibrils. Meanwhile, it
      was highly sensitive to detect as low as 0.1 pM AbetaO in artificial CSF or blood
      plasma. The linear range for AbetaO detection is from 0.1 pM to 10 nM.
      Conclusion: This biosensor could be used as a cost-effective tool for early
      diagnosis of AD due to its high electrochemical performance and bionic structure.

PMID- 29467575
TI  - Nanoscale polysaccharide derivative as an AEG-1 siRNA carrier for effective
      osteosarcoma therapy.
AB  - Background: Nanomedicine, which is the application of nanotechnology in medicine
      to make medical diagnosis and treatment more accurate, has great potential for
      precision medicine. Despite some improvements in nanomedicine, the lack of
      efficient and low-toxic vectors remains a major obstacle. Objective: The aim of
      this study was to prepare an efficient and low-toxic vector which could deliver
      astrocyte elevated gene-1 (AEG-1) small interfering RNA (siRNA; siAEG-1) into
      osteosarcoma cells effectively and silence the targeted gene both in vitro and in
      vivo. Materials and methods: We prepared a novel polysaccharide derivative by
      click conjugation of azidized chitosan with propargyl focal point poly (L-lysine)
      dendrons (PLLD) and subsequent coupling with folic acid (FA; Cs-g-PLLD-FA). We
      confirmed the complexation of siAEG-1and Cs-g-PLLD or Cs-g-PLLD-FA by gel
      retardation assay. We examined the cell cytotoxicity, cell uptake, cell
      proliferation and invasion abilities of Cs-g-PLLD-FA/siAEG-1 in osteosarcoma
      cells. In osteosarcoma 143B cells tumor-bearing mice models, we established the
      therapeutic efficacy and safety of Cs-g-PLLD-FA/siAEG-1. Results: Cs-g-PLLD-FA
      could completely encapsulate siAEG-1 and showed low cytotoxicity in osteosarcoma
      cells and tumour-bearing mice. The Cs-g-PLLD-FA/siAEG-1 nanocomplexes were
      capable of transferring siAEG-1 into osteosarcoma cells efficiently, and the
      knockdown of AEG-1 resulted in the inhibition of tumour cell proliferation and
      invasion. In addition, caudal vein injecting of Cs-g-PLLD-FA/siAEG-1 complexes
      inhibited tumor growth and lung metastasis in tumor-bearing mice by silencing AEG
      1 and regulating MMP-2/9. Conclusion: In summary, Cs-g-PLLD-FA nanoparticles are
      a promising system for the effective delivery of AEG-1 siRNA for treating
      osteosarcoma.

PMID- 29467576
TI  - Mitochondrial genome variability: the effect on cellular functional activity.
AB  - Mitochondria are the key players in cell metabolism, calcium homeostasis, and
      reactive oxygen species (ROS) production. Mitochondrial genome alterations are
      reported to be associated with numerous human disorders affecting nearly all
      tissues. In this review, we discuss the available information on the involvement
      of mitochondrial DNA (mtDNA) mutations in cell dysfunction.

PMID- 29467578
TI  - Cholesterol-Binding Sites in GIRK Channels: The Devil is in the Details.
AB  - In recent years, it has become evident that cholesterol plays a direct role in
      the modulation of a variety of ion channels. In most cases, cholesterol
      downregulates channel activity. In contrast, our earlier studies have
      demonstrated that atrial G protein inwardly rectifying potassium (GIRK) channels
      are upregulated by cholesterol. Recently, we have shown that hippocampal GIRK
      currents are also upregulated by cholesterol. A combined computational
      experimental approach pointed to putative cholesterol-binding sites in the
      transmembrane domain of the GIRK2 channel, the primary subunit in hippocampal
      GIRK channels. In particular, the principal cholesterol-binding site was located
      in the center of the transmembrane domain in between the inner and outer alpha
      helices of 2 adjacent subunits. Further studies pointed to a similar cholesterol
      binding site in GIRK4, a major subunit in atrial GIRK channels. However, a close
      look at a sequence alignment of the transmembrane helices of the 2 channels
      reveals surprising differences among the residues that interact with the
      cholesterol molecule in these 2 channels. Here, we compare the residues that form
      putative cholesterol-binding sites in GIRK2 and GIRK4 and discuss the
      similarities and differences among them.

PMID- 29467577
TI  - Human Immunodeficiency Virus in the Brain-Culprit or Facilitator?
AB  - Introduction: Human immunodeficiency virus (HIV) enters the brain early, where it
      can persist, evolve, and become compartmentalized. Central nervous system (CNS)
      disease can be attributed to HIV alone or to the complex interplay between the
      virus and other neurotropic pathogens. Aim: The current review aims to describe
      the direct impact of HIV on the brain as well as its relationship with other
      pathogens from a practitioner's perspective, to provide a general clinical
      overview, brief workup, and, whenever possible, treatment guidance. Methods: A
      review of PubMed was conducted to identify studies on neuropathogenesis of HIV in
      relation to host responses. Furthermore, the interaction between the CNS
      pathogens and the host damage responses were revised in the setting of advanced
      and also well-controlled HIV infection. Results: Similar to other pathogens, HIV
      leads to CNS immune activation, inflammation, and viral persistence. Therefore,
      almost half of the infected individuals present with neurocognitive disorders,
      albeit mild. Compartmentalized HIV in the CNS can be responsible in a minority of
      cases for the dramatic presentation of symptomatic HIV escape. Disruption of the
      immune system secondary to HIV may reactivate latent infections or allow new
      pathogens to enter the CNS. Opportunistic infections with an inflammatory
      component are associated with elevated HIV loads in the cerebrospinal fluid and
      also with greater cognitive impairment. The inflammatory immune reconstitution
      syndrome associated with CNS opportunistic infections can be a life-threatening
      condition, which needs to be recognized and managed by efficiently controlling
      the pathogen burden and timely balanced combination antiretroviral therapy.
      Latent neurotropic pathogens can reactivate in the brain and mimic HIV-associated
      severe neurological diseases or contribute to neurocognitive impairment in the
      setting of stable HIV infection. Conclusions: As HIV can be responsible for
      considerable brain damage directly or by facilitating other pathogens, more
      effort is needed to recognize and manage HIV-associated CNS disorders and to
      eventually target HIV eradication from the brain.

PMID- 29467579
TI  - Viral and Bacterial Etiologies of Acute Respiratory Infections Among Children
      Under 5 Years in Senegal.
AB  - Acute respiratory infections (ARIs) are the leading cause of infectious disease
      related morbidity, hospitalization, and morbidity among children worldwide. This
      study aimed to assess the viral and bacterial causes of ARI morbidity and
      mortality in children under 5 years in Senegal. Nasopharyngeal samples were
      collected from children under 5 years who had ARI. Viruses and bacteria were
      identified using multiplex real-time reverse transcription-polymerase chain
      reaction and conventional biochemical techniques, respectively. Adenovirus was
      the most prevalent virus (50%; n = 81), followed by influenza virus (45.68%, n =
      74), rhinovirus (40.12%; n = 65), enterovirus (25.31%; n = 41), and respiratory
      syncytial virus (16.05%; n = 26), whereas Streptococcus pneumoniae (17%; n = 29),
      Moraxella catarrhalis (15.43%; n = 25), and Haemophilus influenzae (8.02%; n =
      13) were the most commonly isolated bacteria. Virus pathogens seem more likely to
      be more prevalent in our settings and were often associated with bacteria and S.
      pneumoniae (6%; 16) coinfection.

PMID- 29467581
TI  - Tetrasomy 18p: case report and review of literature.
AB  - Tetrasomy 18p syndrome (Online Mendelian Inheritance in Man 614290) is a very
      rare chromosomal disorder that is caused by the presence of isochromosome 18p,
      which is a supernumerary marker composed of two copies of the p arm of chromosome
      18. Most tetrasomy 18p cases are de novo cases; however, familial cases have also
      been reported. It is characterized mainly by developmental delays, cognitive
      impairment, hypotonia, typical dysmorphic features, and other anomalies. Herein,
      we report de novo tetrasomy 18p in a 9-month-old boy with dysmorphic features,
      microcephaly, growth delay, hypotonia, and cerebellar and renal malformations. We
      compared our case with previously reported ones in the literature. Clinicians
      should consider tetrasomy 18p in any individual with dysmorphic features and
      cardiac, skeletal, and renal abnormalities. To the best of our knowledge, we
      report for the first time an association of this syndrome with partial agenesis
      of cerebellar vermis.

PMID- 29467580
TI  - History of Morgellons disease: from delusion to definition.
AB  - Morgellons disease (MD) is a skin condition characterized by the presence of
      multicolored filaments that lie under, are embedded in, or project from skin.
      Although the condition may have a longer history, disease matching the above
      description was first reported in the US in 2002. Since that time, the condition
      that we know as MD has become a polemic topic. Because individuals afflicted with
      the disease may have crawling or stinging sensations and sometimes believe they
      have an insect or parasite infestation, most medical practitioners consider MD a
      purely delusional disorder. Clinical studies supporting the hypothesis that MD is
      exclusively delusional in origin have considerable methodological flaws and often
      neglect the fact that mental disorders can result from underlying somatic
      illness. In contrast, rigorous experimental investigations show that this skin
      affliction results from a physiological response to the presence of an infectious
      agent. Recent studies from that point of view show an association between MD and
      spirochetal infection in humans, cattle, and dogs. These investigations have
      determined that the cutaneous filaments are not implanted textile fibers, but are
      composed of the cellular proteins keratin and collagen and result from
      overproduction of these filaments in response to spirochetal infection. Further
      studies of the genetics, pathogenesis, and treatment of MD are warranted.

PMID- 29467582
TI  - Neoadjuvant chemotherapy among patients treated for nonmetastatic breast cancer
      in a population with a high HIV prevalence in Johannesburg, South Africa.
AB  - Background: Neoadjuvant (primary) chemotherapy (NACT) is the standard of care for
      locally advanced breast cancer. It also allows for the short-term assessment of
      chemotherapy response; a pathological complete responses correspond to improved
      long-term breast cancer outcomes. In sub-Saharan Africa, many patients are
      diagnosed with large nonresectable tumors. We examined NACT use in breast cancer
      patients who visited public hospitals in Johannesburg, South Africa. Methods: We
      assessed demographic characteristics, tumor stage and grade, hormone receptor
      status, and human immunodeficiency virus (HIV) status of female patients
      diagnosed with nonmetastatic invasive carcinoma of the breast at Chris Hani
      Baragwanath Academic Hospital between January 1, 2009, and December 31, 2011. The
      patients received neoadjuvant, adjuvant, or no chemotherapy. Trastuzumab was
      unavailable. We developed logistic regression models to analyze the factors
      associated with NACT receipt in these patients. Results: Of 554 women with
      nonmetastatic breast cancer, the median age at diagnosis was 52 years (range: 28
      88 years). Only 5.8% of patients were diagnosed with stage I disease; 49.3% and
      44.9% were diagnosed with stages II and III, respectively. Most patients had
      hormone-responsive tumors: luminal A, 38.1%; luminal B1 (human epidermal growth
      factor receptor 2 [HER2]-negative and high grade), 12.5%, and luminal B2 (HER2
      positive any grade), 11.6%; 11.6% had a HER2-enriched tumor and 20.6% a triple
      negative tumor. Eighty (14.4%) patients were HIV-positive. In total, 195 patients
      (35.2%) received NACT, 264 (47.7%) patients received adjuvant chemotherapy, and
      95 patients (17.1%) received no chemotherapy, including 62 (11.2%) patients who
      received only hormonal therapy. Of patients receiving NACT, 125 (64.1%) were
      evaluable for clinical response. Eighty (64.0%) patients had a clinically
      significant response; 19 (15.2%) patients had a stable disease, and 26 (20.8%)
      patients had a progressive disease. Multivariate analysis showed age <40 years
      and disease stage to be independently associated with the receipt of NACT.
      Conclusion: Most women receiving NACT with available response data showed a
      clinical benefit. Stage III disease at diagnosis and age <40 years were
      predictors of neoadjuvant versus adjuvant chemotherapy treatment.

PMID- 29467583
TI  - Bone metastasis pattern in initial metastatic breast cancer: a population-based
      study.
AB  - Purpose: Bone is one of the most common sites of breast cancer metastasis, and
      population-based studies of patients with bone metastasis in initial metastatic
      breast cancer (MBC) are lacking. Materials and methods: From 2010 to 2013,
      245,707 breast cancer patients and 8901 patients diagnosed with initial bone
      metastasis were identified by Surveillance, Epidemiology, and End Results
      database of the National Cancer Institute. Multivariate logistic and Cox
      regression were used to identify predictive factors for the presence of bone
      metastasis and prognosis factors. Kaplan-Meier method and log-rank test were used
      for survival analysis. Results: Eight thousand nine hundred one patients with
      initial MBC had bone involvement, accounting for 3.6% of the entire cohort and
      62.5% of the patients with initial MBC. Also, 70.5% of patients with bone
      metastasis were hormone receptor (HR) positive (HR+/human epidermal growth factor
      receptor 2 [HER2]-: 57.6%; HR+/HER2+: 12.9%). Patients with initial bone
      metastasis had a better 5-year survival rate compared to those with initial
      brain, liver, or lung metastasis. HR+/HER2- and HR+/HER2+ breast cancer had a
      propensity of bone metastasis in the entire cohort and were correlated with
      better prognosis in patients with initial bone metastasis. Local surgery had
      significantly improved overall survival in initial MBC patients with bone
      metastasis. Conclusion: Our study has provided population-based estimates of
      epidemiologic characteristics and prognosis in patients with bone metastasis at
      the time of breast cancer diagnosis. These findings would lend support to optimal
      surveillance and treatment of bone metastasis in breast cancer.

PMID- 29467584
TI  - PCORnet's Collaborative Research Groups.
AB  - The Patient-Centered Outcomes Research Institute (PCORI) launched a multi
      institutional "network of networks" in 2013 - Patient-Centered Clinical Research
      Network (PCORnet) - that is designed to conduct clinical research that is faster,
      less expensive, and more responsive to the information needs of patients and
      clinicians. To enhance cross-network and cross-institutional collaboration and
      catalyze the use of PCORnet, PCORI has supported formation of 11 Collaborative
      Research Groups focusing on specific disease types (e.g., cardiovascular health
      and cancer) or particular patient populations (e.g., pediatrics and health
      disparities). PCORnet's Collaborative Research Groups are establishing research
      priorities within these focus areas, establishing relationships with potential
      funders, and supporting development of specific research projects that will use
      PCORnet resources. PCORnet remains a complex, multilevel, and heterogeneous
      network that is still maturing and building a diverse portfolio of observational
      and interventional people-centered research; engaging with PCORnet can be
      daunting, particularly for outside investigators. We believe the Collaborative
      Research Groups are stimulating interest and helping investigators navigate the
      complexity, but only time will tell if these efforts will bear fruit in terms of
      funded multicenter PCORnet projects.

PMID- 29467585
TI  - Integrating Circulating Immunological and Sputum Biomarkers for the Early
      Detection of Lung Cancer.
AB  - We have demonstrated that assessments of microRNA (miRNA) expressions in
      circulating peripheral blood mononucleated cell (PBMC) and sputum specimens,
      respectively, may help diagnose lung cancer. To assess the individual and
      combined analysis of the miRNAs across the different body fluids for lung cancer
      early detection, we analyse a panel of 3 sputum miRNAs (miRs-21, 31, and 210) and
      a panel of 2 PBMC miRNAs (miRs-19b-3p and 29b-3p) in a discovery cohort of 68
      patients with lung cancer and 66 cancer-free smokers. We find that integrating 2
      sputum miRNAs (miRs-31 and 210) and 1 PBMC miRNA (miR-19b-3p) has higher
      sensitivity (86.8%) and specificity (92.4%) compared with the individual panels.
      The synergistic value of the integrated panel of 3 biomarkers is confirmed in a
      validation cohort, independent of stage and histological type of lung cancer, and
      patients' age, sex, and ethnicity. Integrating circulating immunological and
      sputum biomarkers could improve the early detection of lung cancer.

PMID- 29467586
TI  - An Observational 1-Month Trial on the Efficacy and Safety of Promerim for
      Improving Knee Joint.
AB  - Objective: This study was conducted to evaluate the efficacy and tolerability of
      the oral intake of promerim in the elimination of acute pain and discomfort
      associated with knee osteoarthritis (OA). Methods: Single-center, 1-month,
      prospective, observational clinical trial. A total of 92 patients not older than
      70 years were included. Patients were offered to use 720-mg promerim for the
      first 15 days after admission after breakfast and then 360 mg for the second 15
      days. All patients were analyzed with the visual analog scale (VAS) for pain,
      which ranges from 0 to 10, and the Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) score before the start of treatment and 1 month
      after the start. Statistical analysis was performed by SPSS 15.0 software. An
      alpha level of P < .05 was assumed to be statistically significant. Results: This
      study comprised 92 patients (69 women and 23 men) with a mean age of 51.5 (range:
      40-69) years. Before treatment, the mean VAS score was 5.6 +/- 1.1, and after
      treatment, the mean VAS score was 2.6 +/- 1.7. Treatment with promerim
      consistently showed a significant decrease in the VAS score (P < .001). The mean
      WOMAC score of the patients was 46.4 +/- 8.2 before treatment. After treatment,
      the mean WOMAC score was 72.1 +/- 14.4. Treatment with promerim consistently
      showed a significant increase in the WOMAC score (P < .001). Conclusions: The
      results of this single-center, open-label clinical study demonstrate that
      promerim is a viable natural treatment option for treating knee OA. We recommend
      that 720-mg promerim taken once daily for the first 15 days after admission and
      360 mg taken once daily for the next 15 days significantly and rapidly reduced
      composite pain and stiffness in the knee OA within 1 month.

PMID- 29467587
TI  - Management of Tizanidine Withdrawal Syndrome: A Case Report.
AB  - Most drugs that act on the central nervous system (CNS) require dose titration to
      avoid withdrawal syndrome. Tizanidine withdrawal syndrome is caused by adrenergic
      discharge due to its alpha2-agonist mechanism and is characterized by
      hypertension, reflex tachycardia, hypertonicity, and anxiety. Although tizanidine
      withdrawal syndrome is mentioned as a potential side effect of cessation, it is
      not common and there have been few reports. We present the case of a 31-year-old
      woman with tizanidine withdrawal syndrome after discontinuing medication
      prescribed for a muscle contracture (tizanidine). She showed high adrenergic
      activity with nausea, vomiting, generalized tremor, dysthermia, hypertension, and
      tachycardia. Symptoms were reversed and successful reweaning was achieved by
      restarting tizanidine followed by slow downward titration. Withdrawal syndrome
      should be considered when drugs targeting the CNS are suddenly stopped. Weaning
      regimens should be closely monitored for acute withdrawal reactions.

PMID- 29467588
TI  - Pulmonary Arterial Enlargement is Associated With Acute Chest Pain in Patients
      Without Obstructive Coronary Artery Disease.
AB  - Background: Pulmonary hypertension (PH) is an underdiagnosed cause for chest pain
      in patients without significant coronary artery disease (CAD). Studies showed
      that enlarged pulmonary arterial (PA) and right ventricular chamber sizes
      correlate with the severity of PH. Therefore, we studied the association between
      chest pain, right ventricular dimensions (RVDs), and PA size on coronary coronary
      tomographic angiography (CCTA). Methods: The CCTA of 87 patients presenting with
      chest pain without evidence of obstructive CAD was examined. The PA diameter
      (PAD), right atrial dimension (RAD), and RVD were measured. A comparative control
      cohort included 31 patients who presented without cardiopulmonary complaints and
      underwent thoracic CT. The risk for obstructive sleep apnea (OSA) was assessed
      using STOP-BANG questionnaires. Results: Patients with chest pain without
      obstructive CAD showed markedly dilated right atrial and ventricular chambers
      compared with standard parameters (right atrium: 48 +/- 6.4 mm; right ventricle
      long axis: 61 +/- 9.5 mm). When comparing chest pain vs non-chest pain group,
      respectively, the mean PAD measured 25.92 +/- 0.43 mm vs 22.89 +/- 0.38 mm (P <
      .001), RAD2 measured 40.1423 +/- 0.7108 mm vs 34.8800 +/- 1.0245 mm (P = .0048),
      and RVD2 measured 31.7729 +/- 0.7299 mm vs 27.6379 +/- 1.6178 mm (P = .034).
      Chest pain was associated with higher PAD (odds ratio [OR]: 11.11, P < .05) after
      adjusting for age, sex, body mass index, history of hypertension, hyperlipidemia,
      congestive heart failure, chronic obstructive pulmonary disease, OSA, and
      smoking. The chest pain group had a mean STOP-BANG score of 3.9 +/- 1.8 in all
      patients, and 3.62 +/- 0.20 in patients without known history of OSA,
      representing an elevated risk index for the disease. Conclusions: In patients
      presenting with chest pain without obstructive CAD on CCTA, there is a strong
      association between the presence of chest pain and enlarged PAD. They also
      represent a high-risk group for OSA.

PMID- 29467589
TI  - Cabergoline-Induced Pneumocephalus Following Treatment for Giant Invasive
      Macroprolactinoma Presenting With Spontaneous Cerebrospinal Fluid Rhinorrhea.
AB  - Cerebrospinal fluid (CSF) rhinorrhea is rarely reported as the first presenting
      feature of giant invasive macroprolactinomas. Cerebrospinal fluid rhinorrhea is
      usually reported as a complication of trauma, neurosurgical, and skull-based
      procedures (such as pituitary surgery or radiations), and less frequently after
      medical treatment with dopamine agonists (DAs) for macroprolactinomas. This
      phenomenon results from fistula creation that communicates between the
      subarachnoid space and the nasal cavity. Meanwhile, pneumocephalus is another
      well-recognized complication after transsphenoidal surgery for pituitary
      macroadenomas. This entity may present with nausea, vomiting, headache,
      dizziness, and more seriously with seizures and/or a decreased level of
      consciousness if tension pneumocephalus develops. Case reports about the
      occurrence of spontaneous pneumocephalus after medical treatment with DAs without
      prior surgical interventions are scarce in the literature. Our index case is a
      young man who was recently diagnosed with a giant invasive prolactin-secreting
      pituitary macroadenoma with skull base destruction. A few months before this
      diagnosis, he presented with spontaneous CSF rhinorrhea with no history of
      previous medical or surgical treatment. In this case report, we report an
      uncommon presentation for giant invasive macroprolactinoma with a CSF leak
      treated with cabergoline that was subsequently complicated by meningitis and
      pneumocephalus. This is a very rare complication of cabergoline therapy, which
      occurred approximately 1 month after treatment initiation.

PMID- 29467590
TI  - PAUSE: A Patient-Centric Tool to Support Patient-Provider Engagement on
      Menopause.
AB  - There are powerful demographic, political, and environmental trends shaping
      women's health. Increases in life expectancy, literacy, and empowerment are
      fueling expansions in education and advocacy. Research and development focuses on
      women's health and fertility across an expanded age spectrum. There is also a
      cultural emphasis on antiaging and aesthetics. In parallel, the digital
      revolution is changing how health care is accessed by and delivered to women. A
      women's journey through menopause is at the crossroads of these transformations.
      Medical and social platforms encourage women to embrace menopause as a pivotal
      life stage. Yet, many women are reticent to discuss "the transition" due to
      embarrassment about its symptoms, lack of awareness of its physical
      manifestations, or fear of aging. We introduce a patient-centric framework to
      support patient-provider engagement on menopause: prevention, anxiety, urogenital
      symptoms, vasomotor symptoms, and education. Although not comprehensive, PAUSE
      represents an acronym and reminder to focus a portion of the medical interaction
      on menopause.

PMID- 29467591
TI  - Whole exome sequencing reveals novel somatic alterations in neuroblastoma
      patients with chemotherapy.
AB  - Background: We ought to explore the acquired somatic alterations, shedding light
      on genetic basis of somatic alterations in NB patients with chemotherapy.
      Methods: Marrow blood samples from NB patients were collected before treatment,
      after the 2nd and 4th chemotherapy for baseline research and continuous
      monitoring by whole exome sequencing. Plasma cell free DNA (cfDNA) was prepared
      for baseline research. Finger nail cells were extracted as self control. The
      clinical data was analyzed. Results: From December 2014 to February 2016, 27
      cases of children with stage IV NB were diagnosed. The follow up time ranged from
      5 to 25 months, with a median follow up time of 17 months, 20 patients were
      stable, one patient died of pulmonary embolism during surgery, six patients died
      of disease progression. Marrow blood whole exome sequencing demonstrated that
      several novel somatic mutations were identified in all three trios comply or
      against the trendy of tumor size variation. Of note, six recurrent mutations in
      bromodomain PHD finger transcription factor (BPTF) were identified in nine NB
      patients under the continuous monitoring. The mutation rates variation was
      positively correlated to tumor size (CC = 0.428, P = 0.021), and patients with
      BPTF mutation may have a worse prognosis compared with wild type. Meanwhile,
      CGREF1, CUX2, GP1BA, SLC45A1 and TRA2A were mutated with the trendy oppose as
      therapeutic effects. The baseline research in three NB patients demonstrated that
      mutation rate of BPTF, TMCO3, GPRIN2 and C20orf96 in plasma cfDNA were in
      positive correlation with bone marrow genomic DNA (P = 0.001). Conclusions: Our
      study showed that BPTF along with other mutations may function as a biomarker for
      evaluating to effects of chemotherapy to this refractory tumor, and patients with
      BPTF mutation might have a worse prognosis.

PMID- 29467592
TI  - Loss of PIM1 correlates with progression and prognosis of salivary adenoid cystic
      carcinoma (SACC).
AB  - Background: Increasing evidence indicates that PIM1 is a potential prognostic
      marker and target for cancer treatment but its precise mechanisms of action
      remain to be determined in salivary adenoid cystic carcinoma (SACC). This study
      aims to decipher the prognostic and mechanistic role of PIM1 in progression of
      SACC cells and tumor tissues. Methods: A SACC cell line (ACC-M) was transfected
      with shRNA plasmids targeting the PIM1 gene. The expression levels of PIM1, RUNX3
      and p21 were measured by quantitative real-time PCR and western blot. Subcellular
      translocalization of RUNX3 and p21 proteins was assessed using
      immunofluorescence, and cell cycle phase was quantified using flow cytometry. A
      total of 97 SACC patients were retrospectively analyzed by clinicopathologic
      characteristics and survival outcomes. Results: After down-regulation of PIM1 in
      ACC-M cells, RUNX3 and p21 proteins were translocated from cytoplasm to nucleus,
      with a decrease of p21 expression and increase of G0/G1 phase cells. PIM1 and
      RUNX3 levels show a distinct covariance. PIM1 is associated with T-status, lymph
      node involvement, nerve invasion, and distant metastasis in SACC tissues.
      Patients with low PIM1 level had a better outcome than those with higher PIM1
      level. Conclusions: PIM1 is multifunctional in ACC-M cells and it serves as a
      neoteric therapeutic target and potential prognostic marker for SACC patients.

PMID- 29467593
TI  - Depletion of membrane cholesterol compromised caspase-8 imparts in autophagy
      induction and inhibition of cell migration in cancer cells.
AB  - Background: Cholesterol in lipid raft plays crucial role on cancer cell survival
      during metastasis of cancer cells. Cancer cells are reported to enrich
      cholesterol in lipid raft which make them more susceptible to cell death after
      cholesterol depletion than normal cells. Methyl-beta-cyclodextrin (MbetaCD), an
      amphipathic polysaccharide known to deplete the membrane cholesterol, induces
      cell death selectively in cancer cells. Present work was designed to identify the
      major form of programmed cell death in membrane cholesterol depleted cancer cells
      (MDA-MB 231 and 4T1) and its impact on migration efficiency of cancer cells.
      Methods: Membrane cholesterol alteration and morphological changes in 4T1 and MDA
      MB 231 cancer cells by MbetaCD were measured by fluorescent microscopy. Cell
      death and cell proliferation were observed by PI, AO/EB and MTT assay
      respectively. Programme cell death was confirmed by flow cytometer. Caspase
      activation was assessed by MTT and PI after treatments with Z-VAD [OME]-FMK,
      mitomycin c and cycloheximide. Necroptosis, autophagy, pyroptosis and paraptosis
      were examined by cell proliferation assay and flow cytometry. Relative
      quantitation of mRNA of caspase-8, necroptosis and autophagy genes were
      performed. Migration efficiency of cancer cells were determined by wound healing
      assay. Results: We found caspase independent cell death in cholesterol depleted
      MDA-MB 231 cells which was reduced by (3-MA) an autophagy inhibitor. Membrane
      cholesterol depletion neither induces necroptosis, paraptosis nor pyroptosis in
      MDA-MB 231 cells. Subsequent activation of caspase-8 after co-incubation of
      mitomycin c and cycloheximide separately, restored the cell viability in
      cholesterol depleted MDA-MB 231 cells. Down regulation of caspase-8 mRNA in
      cholesterol depleted cancer cells ensures that caspase-8 indirectly promotes the
      induction of autophagy. In another experiment we have demonstrated that membrane
      cholesterol depletion reduces the migration efficiency in cancer cells.
      Conclusion: Together our experimental data suggests that membrane cholesterol is
      the crucial for the recruitment and activation of caspase-8 as well as its non
      apoptotic functions in cancer cells. Enriched cholesterol in lipid raft of cancer
      cells may be regulating the cross talk between caspase-8 and autophagy
      machineries to promote their survival and migration. Therefore it can be explored
      to understand and address the issues of chemotherapeutic and drugs resistance.

PMID- 29467594
TI  - Catalase down-regulation in cancer cells exposed to arsenic trioxide is involved
      in their increased sensitivity to a pro-oxidant treatment.
AB  - Background: Pro-oxidant drugs have been proposed for treating certain cancers but
      the resistance developed by cancer cells to oxidative stress limits its potential
      use in clinics. To understand the mechanisms underlying resistance to oxidative
      stress, we found that the chronic exposure to an H2O2-generating system
      (ascorbate/menadione, Asc/Men) or catalase overexpression (CAT3 cells) increased
      the resistance of cancer cells to oxidative stress, likely by increasing the
      antioxidant status of cancer cells. Methods: Modulation of catalase expression
      was performed by either protein overexpression or protein down-regulation using
      siRNA against catalase and aminotriazole as pharmacological inhibitor. The former
      approach was done by transfecting cells with a plasmid construct containing human
      catalase cDNA (CAT3 cells, derived from MCF-7 breast cancer cell line) or by
      generating resistant cells through chronic exposure to an oxidant injury (Resox
      cells). Cell survival was monitored by using the MTT reduction assay and further
      calculation of IC50 values. Protein expression was done by Western blots
      procedures. The formation of reactive oxygen species was performed by flow
      cytometry. The transcriptional activity of human catalase promoter was assessed
      by using transfected cells with a plasmid containing the - 1518/+ 16 promoter
      domain. Results: Using Resox and CAT3 cells (derived from MCF-7 breast cancer
      cell line) as models for cancer resistance to pro-oxidative treatment, we found
      that arsenic trioxide (ATO) remarkably sensitized Resox and CAT3 cells to Asc/Men
      treatment. Since catalase is a key antioxidant enzyme involved in detoxifying
      Asc/Men (as shown by siRNA-mediated catalase knockdown) that is overexpressed in
      resistant cells, we hypothesized that ATO might regulate the expression levels of
      catalase. Consistently, catalase protein level is decreased in Resox cells when
      incubated with ATO likely by a decreased transcriptional activity of the catalase
      promoter. Conclusions: Our findings support the proposal that ATO should be
      administered in combination with pro-oxidant drugs to enhance cancer cell death
      in solid tumors.

PMID- 29467595
TI  - Increased ETV4 expression correlates with estrogen-enhanced proliferation and
      invasiveness of cholangiocarcinoma cells.
AB  - Background: Cholangiocarcinoma (CCA) is one of the worst prognosis cancer. The
      survival time of CCA patients is related to serum estrogen levels and estrogen
      has been found to enhance the proliferation and invasiveness of CCA cells in
      vitro. This has led to the suggestion that estrogen may play an important role in
      the progression of CCA. This study tests the relevance of the previous in vitro
      findings in vivo using a mouse xenograft model of CCA, and investigates possible
      signaling mechanisms involved. Methods: KKU-213 and KKU-139 CCA cell lines were
      used in the experiments, xenografted to nude mice and treated with a potent
      estrogenic agent, 17beta-estradiol (E2), and/or with tamoxifen (TAM), an estrogen
      antagonist. Results: The results demonstrated that E2 could accelerate growth of
      the xenograft-tumor and the effect was inhibited by TAM. PCR array screening of
      E2 responsive genes suggested ETV4 as a promising candidate intracellular
      mediator. ETV4-knockdown CCA cells were generated and these showed a diminished
      responsiveness to E2 in both cell and spheroid proliferation assays, and in
      invasion tests. These results point to ETV4 as a possible mediator of E2
      activated CCA progression and as a potential target of TAM-mediated inhibition.
      Conclusions: Finally, TAM may be suggested as an adjunctive treatment of CCA to
      improve the conventional cytotoxic method with more patient toleration.

PMID- 29467596
TI  - Cost-effectiveness of antiviral prophylaxis during pregnancy for the prevention
      of perinatal hepatitis B infection in South Korea.
AB  - Background: In Korea, hepatitis B virus (HBV) infection accounts for
      approximately 65-75% of HBV-related diseases, such as chronic hepatitis and liver
      cancer, and mother-to-child transmission is presumed to be a major source of the
      infection. To tackle this issue, the Korean government launched the national
      Perinatal Hepatitis B Prevention Program (PHBPP) in 2002. This study analyzed the
      cost-effectiveness of the PHBPP with antiviral prophylaxis compared with the
      current PHBPP and/or universal vaccination, as well as identified the optimal
      strategy to eliminate mother-to-child transmission of HBV in Korea. Methods: A
      decision tree model with the Markov process was developed and simulated over the
      lifetime of a birth cohort in Korea during the year 2014. The current PHBPP
      providing HBV vaccine and hepatitis B immune globulin to neonates born to HBV
      positive mothers was compared against two other strategies, universal vaccination
      of HBV and PHBPP with antiviral prophylaxis, with respect to their costs and
      health outcomes. The Korean National Health Insurance database was investigated
      to estimate the costs of HBV-related diseases and utilization of health
      resources. Costs were assessed from the health care system perspective and
      converted to 2014 US dollars. Health outcome measures were quality-adjusted life
      years (QALYs) and number of HBV-related diseases and deaths. Both costs and QALYs
      were discounted at 5%, following the recommendation of the Health Insurance
      Review & Assessment Service in Korea. The incremental cost-effectiveness ratio
      (ICER) obtained from the analysis was evaluated using the willingness-to-pay
      (WTP) in the Korean society. Results: PHBPP with antiviral prophylaxis in Korea
      was cost-effective compared with the current PHBPP. An introduction of antiviral
      prophylaxis to pregnant women with a high viral load of HBV averted 13 HBV
      related deaths per 100,000 people and saved 82 QALYs in total (ICER:
      $16,159/QALY). Conclusions: Considering that WTP in Korea is $29,000, PHBPP with
      antiviral prophylaxis appears to be a cost-effective strategy. To further
      decrease the burden of perinatal hepatitis B in Korea, adding antiviral
      prophylaxis to PHBPP is recommended.

PMID- 29467597
TI  - [? If it's not documented, it's not done ?: Management indicators of workload can
      leave women's work invisible].
AB  - Historically, eldercare was usually furnished by unpaid women at home. Now that
      women are in paid work, much of this care is given by personal support workers
      (PSWs), usually female. With the massive introduction of management indicators in
      public organisations, a form of organisational silence appears: work is rendered
      invisible. To examine the mechanism involved, we have observed the work of 37
      PSWs in six Ontario residences, and performed interviews. Contrary to the way
      tasks are assigned, PSW work is often done collectively and documentation
      requirements are demanding; documenting can even conflict with direct health
      care. PSWs have insufficient time, so they are sometimes forced to omit data
      showing the challenges of their work. They thus contribute to a vicious circle
      where, unable to document the work they do, they lack resources and must skimp
      even more on documentation.

PMID- 29467599
TI  - Enstrom's Expose of Air Pollution Epidemiology Problems.

PMID- 29467598
TI  - An attempt to induce an immunomodulatory effect in rowers with spirulina extract.
AB  - Background: The aim of this study was to analyze the response of selected
      components of the immune system in rowers to maximal physical exercise, and to
      verify if this response can be modulated by supplementation with spirulina
      (cyanobacterium Spirulina platensis). Method: The double-blind study included 19
      members of the Polish Rowing Team. The subjects were randomly assigned to the
      supplemented group (n = 10), receiving 1500 mg of spirulina extract for 6 weeks,
      or to the placebo group (n = 9). The participants performed a 2000-m test on a
      rowing ergometer at the beginning (1st examination) and at the end of the
      supplementation period (2nd examination). Blood samples were obtained from the
      antecubital vein prior to each exercise test, 1 min after completing the test,
      and after a 24-h recovery period. Subpopulations of T regulatory lymphocytes
      (Tregs) [CD4+/CD25+/CD127-], cytotoxic lymphocytes (CTLs) [CD8+/TCRalphabeta+],
      natural killer (NK) cells [CD3-/CD16+/CD56+] and TCRdeltagamma-positive
      (Tdeltagamma) cells were determined by means of flow cytometry. Results: On the
      2nd examination, athletes from the supplemented group showed neither a post
      exercise increase in Treg count nor a post-recovery decrease in Tdeltagamma cell
      count (both observed in the placebo group), and presented with significantly
      lower values of Treg/CTL prior to and after the exercise. During the same
      examination, rowers from the placebo group showed a significant post-recovery
      increase in Treg/(NK + Tdeltagamma + CTL) ratio, which was absent in the
      supplemented group. Conclusion: The results of this study imply that
      supplementation with spirulina extract may protect athletes against a deficit in
      immune function (especially, anti-infectious function) associated with strenuous
      exercise, and may cause a beneficial shift in "overtraining threshold" preventing
      a radical deterioration of immunity.

PMID- 29467600
TI  - White Matter Tract Segmentation as Multiple Linear Assignment Problems.
AB  - Diffusion magnetic resonance imaging (dMRI) allows to reconstruct the main
      pathways of axons within the white matter of the brain as a set of polylines,
      called streamlines. The set of streamlines of the whole brain is called the
      tractogram. Organizing tractograms into anatomically meaningful structures,
      called tracts, is known as the tract segmentation problem, with important
      applications to neurosurgical planning and tractometry. Automatic tract
      segmentation techniques can be unsupervised or supervised. A common criticism of
      unsupervised methods, like clustering, is that there is no guarantee to obtain
      anatomically meaningful tracts. In this work, we focus on supervised tract
      segmentation, which is driven by prior knowledge from anatomical atlases or from
      examples, i.e., segmented tracts from different subjects. We present a supervised
      tract segmentation method that segments a given tract of interest in the
      tractogram of a new subject using multiple examples as prior information. Our
      proposed tract segmentation method is based on the idea of streamline
      correspondence i.e., on finding corresponding streamlines across different
      tractograms. In the literature, streamline correspondence has been addressed with
      the nearest neighbor (NN) strategy. Differently, here we formulate the problem of
      streamline correspondence as a linear assignment problem (LAP), which is a
      cornerstone of combinatorial optimization. With respect to the NN, the LAP
      introduces a constraint of one-to-one correspondence between streamlines, that
      forces the correspondences to follow the local anatomical differences between the
      example and the target tract, neglected by the NN. In the proposed solution, we
      combined the Jonker-Volgenant algorithm (LAPJV) for solving the LAP together with
      an efficient way of computing the nearest neighbors of a streamline, which
      massively reduces the total amount of computations needed to segment a tract.
      Moreover, we propose a ranking strategy to merge correspondences coming from
      different examples. We validate the proposed method on tractograms generated from
      the human connectome project (HCP) dataset and compare the segmentations with the
      NN method and the ROI-based method. The results show that LAP-based segmentation
      is vastly more accurate than ROI-based segmentation and substantially more
      accurate than the NN strategy. We provide a Free/OpenSource implementation of the
      proposed method.

PMID- 29467601
TI  - The Evolution of Musicality: What Can Be Learned from Language Evolution
      Research?
AB  - Language and music share many commonalities, both as natural phenomena and as
      subjects of intellectual inquiry. Rather than exhaustively reviewing these
      connections, we focus on potential cross-pollination of methodological inquiries
      and attitudes. We highlight areas in which scholarship on the evolution of
      language may inform the evolution of music. We focus on the value of coupled
      empirical and formal methodologies, and on the futility of mysterianism, the
      declining view that the nature, origins and evolution of language cannot be
      addressed empirically. We identify key areas in which the evolution of language
      as a discipline has flourished historically, and suggest ways in which these
      advances can be integrated into the study of the evolution of music.

PMID- 29467602
TI  - Feature Selection Methods for Robust Decoding of Finger Movements in a Non-human
      Primate.
AB  - Objective: The performance of machine learning algorithms used for neural
      decoding of dexterous tasks may be impeded due to problems arising when dealing
      with high-dimensional data. The objective of feature selection algorithms is to
      choose a near-optimal subset of features from the original feature space to
      improve the performance of the decoding algorithm. The aim of our study was to
      compare the effects of four feature selection techniques, Wilcoxon signed-rank
      test, Relative Importance, Principal Component Analysis (PCA), and Mutual
      Information Maximization on SVM classification performance for a dexterous
      decoding task. Approach: A nonhuman primate (NHP) was trained to perform small
      coordinated movements-similar to typing. An array of microelectrodes was
      implanted in the hand area of the motor cortex of the NHP and used to record
      action potentials (AP) during finger movements. A Support Vector Machine (SVM)
      was used to classify which finger movement the NHP was making based upon AP
      firing rates. We used the SVM classification to examine the functional parameters
      of (i) robustness to simulated failure and (ii) longevity of classification. We
      also compared the effect of using isolated-neuron and multi-unit firing rates as
      the feature vector supplied to the SVM. Main results: The average decoding
      accuracy for multi-unit features and single-unit features using Mutual
      Information Maximization (MIM) across 47 sessions was 96.74 +/- 3.5% and 97.65 +/
      3.36% respectively. The reduction in decoding accuracy between using 100% of the
      features and 10% of features based on MIM was 45.56% (from 93.7 to 51.09%) and
      4.75% (from 95.32 to 90.79%) for multi-unit and single-unit features
      respectively. MIM had best performance compared to other feature selection
      methods. Significance: These results suggest improved decoding performance can be
      achieved by using optimally selected features. The results based on clinically
      relevant performance metrics also suggest that the decoding algorithm can be made
      robust by using optimal features and feature selection algorithms. We believe
      that even a few percent increase in performance is important and improves the
      decoding accuracy of the machine learning algorithm potentially increasing the
      ease of use of a brain machine interface.

PMID- 29467603
TI  - Cognitive Functions and Neurodevelopmental Disorders Involving the Prefrontal
      Cortex and Mediodorsal Thalamus.
AB  - The mediodorsal nucleus of the thalamus (MD) has been implicated in executive
      functions (such as planning, cognitive control, working memory, and decision
      making) because of its significant interconnectivity with the prefrontal cortex
      (PFC). Yet, whilst the roles of the PFC have been extensively studied, how the MD
      contributes to these cognitive functions remains relatively unclear. Recently,
      causal evidence in monkeys has demonstrated that in everyday tasks involving
      rapid updating (e.g., while learning something new, making decisions, or planning
      the next move), the MD and frontal cortex are working in close partnership.
      Furthermore, researchers studying the MD in rodents have been able to probe the
      underlying mechanisms of this relationship to give greater insights into how the
      frontal cortex and MD might interact during the performance of these essential
      tasks. This review summarizes the circuitry and known neuromodulators of the MD,
      and considers the most recent behavioral, cognitive, and neurophysiological
      studies conducted in monkeys and rodents; in total, this evidence demonstrates
      that MD makes a critical contribution to cognitive functions. We propose that
      communication occurs between the MD and the frontal cortex in an ongoing, fluid
      manner during rapid cognitive operations, via the means of efference copies of
      messages passed through transthalamic routes; the conductance of these messages
      may be modulated by other brain structures interconnected to the MD. This is
      similar to the way in which other thalamic structures have been suggested to
      carry out forward modeling associated with rapid motor responding and visual
      processing. Given this, and the marked thalamic pathophysiology now identified in
      many neuropsychiatric disorders, we suggest that changes in the different
      subdivisions of the MD and their interconnections with the cortex could plausibly
      give rise to a number of the otherwise disparate symptoms (including changes to
      olfaction and cognitive functioning) that are associated with many different
      neuropsychiatric disorders. In particular, we will focus here on the cognitive
      symptoms of schizophrenia and suggest testable hypotheses about how changes to MD
      frontal cortex interactions may affect cognitive processes in this disorder.

PMID- 29467604
TI  - Investigating Misophonia: A Review of the Empirical Literature, Clinical
      Implications, and a Research Agenda.
AB  - Misophonia is a neurobehavioral syndrome phenotypically characterized by
      heightened autonomic nervous system arousal and negative emotional reactivity (e.
      g., irritation, anger, anxiety) in response to a decreased tolerance for specific
      sounds. The aims of this review are to (a) characterize the current state of the
      field of research on misophonia, (b) highlight what can be inferred from the
      small research literature to inform treatment of individuals with misophonia, and
      (c) outline an agenda for research on this topic. We extend previous reviews on
      this topic by critically reviewing the research investigating mechanisms of
      misophonia and differences between misophonia and other conditions. In addition,
      we integrate this small but growing literature with basic and applied research
      from other literatures in a cross-disciplinary manner.

PMID- 29467607
TI  - Understanding the Generation of Network Bursts by Adaptive Oscillatory Neurons.
AB  - Experimental and numerical studies have revealed that isolated populations of
      oscillatory neurons can spontaneously synchronize and generate periodic bursts
      involving the whole network. Such a behavior has notably been observed for
      cultured neurons in rodent's cortex or hippocampus. We show here that a
      sufficient condition for this network bursting is the presence of an excitatory
      population of oscillatory neurons which displays spike-driven adaptation. We
      provide an analytic model to analyze network bursts generated by coupled adaptive
      exponential integrate-and-fire neurons. We show that, for strong synaptic
      coupling, intrinsically tonic spiking neurons evolve to reach a synchronized
      intermittent bursting state. The presence of inhibitory neurons or plastic
      synapses can then modulate this dynamics in many ways but is not necessary for
      its appearance. Thanks to a simple self-consistent equation, our model gives an
      intuitive and semi-quantitative tool to understand the bursting behavior.
      Furthermore, it suggests that after-hyperpolarization currents are sufficient to
      explain bursting termination. Through a thorough mapping between the theoretical
      parameters and ion-channel properties, we discuss the biological mechanisms that
      could be involved and the relevance of the explored parameter-space. Such an
      insight enables us to propose experimentally-testable predictions regarding how
      blocking fast, medium or slow after-hyperpolarization channels would affect the
      firing rate and burst duration, as well as the interburst interval.

PMID- 29467605
TI  - Challenges for Alzheimer's Disease Therapy: Insights from Novel Mechanisms Beyond
      Memory Defects.
AB  - Alzheimer's disease (AD), the most common form of dementia in late life, will
      become even more prevalent by midcentury, constituting a major global health
      concern with huge implications for individuals and society. Despite scientific
      breakthroughs during the past decades that have expanded our knowledge on the
      cellular and molecular bases of AD, therapies that effectively halt disease
      progression are still lacking, and focused efforts are needed to address this
      public health challenge. Because AD is classically recognized as a disease of
      memory, studies have mainly focused on investigating memory-associated brain
      defects. However, compelling evidence has indicated that additional brain
      regions, not classically linked to memory, are also affected in the course of
      disease. In this review, we outline the current understanding of key
      pathophysiological mechanisms in AD and their clinical manifestation. We also
      highlight how considering the complex nature of AD pathogenesis, and exploring
      repurposed drug approaches can pave the road toward the development of novel
      therapeutics for AD.

PMID- 29467606
TI  - Integrating Brain and Biomechanical Models-A New Paradigm for Understanding Neuro
      muscular Control.
AB  - To date, realistic models of how the central nervous system governs behavior have
      been restricted in scope to the brain, brainstem or spinal column, as if these
      existed as disembodied organs. Further, the model is often exercised in relation
      to an in vivo physiological experiment with input comprising an impulse, a
      periodic signal or constant activation, and output as a pattern of neural
      activity in one or more neural populations. Any link to behavior is inferred only
      indirectly via these activity patterns. We argue that to discover the principles
      of operation of neural systems, it is necessary to express their behavior in
      terms of physical movements of a realistic motor system, and to supply inputs
      that mimic sensory experience. To do this with confidence, we must connect our
      brain models to neuro-muscular models and provide relevant visual and
      proprioceptive feedback signals, thereby closing the loop of the simulation. This
      paper describes an effort to develop just such an integrated brain and
      biomechanical system using a number of pre-existing models. It describes a model
      of the saccadic oculomotor system incorporating a neuromuscular model of the eye
      and its six extraocular muscles. The position of the eye determines how
      illumination of a retinotopic input population projects information about the
      location of a saccade target into the system. A pre-existing saccadic burst
      generator model was incorporated into the system, which generated motoneuron
      activity patterns suitable for driving the biomechanical eye. The model was
      demonstrated to make accurate saccades to a target luminance under a set of
      environmental constraints. Challenges encountered in the development of this
      model showed the importance of this integrated modeling approach. Thus, we
      exposed shortcomings in individual model components which were only apparent when
      these were supplied with the more plausible inputs available in a closed loop
      design. Consequently we were able to suggest missing functionality which the
      system would require to reproduce more realistic behavior. The construction of
      such closed-loop animal models constitutes a new paradigm of computational
      neurobehavior and promises a more thoroughgoing approach to our understanding of
      the brain's function as a controller for movement and behavior.

PMID- 29467608
TI  - Understanding the Role of Adenosine A2AR Heteroreceptor Complexes in
      Neurodegeneration and Neuroinflammation.
AB  - Adenosine is a nucleoside mainly formed by degradation of ATP, located
      intracellularly or extracellularly, and acts as a neuromodulator. It operates as
      a volume transmission signal through diffusion and flow in the extracellular
      space to modulate the activity of both glial cells and neurons. The effects of
      adenosine are mediated via four adenosine receptor subtypes: A1R, A2AR, A2BR,
      A3R. The A2AR has a wide-spread distribution but it is especially enriched in the
      ventral and dorsal striatum where it is mainly located in the striato-pallidal
      GABA neurons at a synaptic and extrasynaptic location. A number of A2AR
      heteroreceptor complexes exist in the striatum. The existence of A2AR-D2R
      heteroreceptor complexes with antagonistic A2AR-D2R interactions in the striato
      pallidal GABA neurons is well-known with A2AR activation inhibiting Gi/o mediated
      signaling of D2Rs. A2AR-mGluR5 heteroreceptor complexes were also found in with
      synergistic receptor-receptor interactions enhancing the inhibition of the D2R
      protomer signaling. They are located mainly in extrasynaptic regions of the
      striato-pallidal GABA neurons. Results recently demonstrated the existence of
      brain A2AR-A2BR heteroreceptor complexes, in which A2BR protomer constitutively
      inhibited the function of the A2AR protomer. These adenosine A2AR heteroreceptor
      complexes may modulate alpha-synuclein aggregation and toxicity through
      postulated bidirectional direct interactions leading to marked increases in A2AR
      signaling both in nerve cells and microglia. It is of high interest that
      formation of A2AR-A2ABR heteroreceptor complexes provides a brake on A2AR
      recognition and signaling opening up a novel strategy for treatment of A2AR
      mediated neurodegeneration.

PMID- 29467609
TI  - Phospho-Tau Bar Code: Analysis of Phosphoisotypes of Tau and Its Application to
      Tauopathy.
AB  - Tau is a microtubule-associated protein which regulates the assembly and
      stability of microtubules in the axons of neurons. Tau is also a major component
      of neurofibrillary tangles (NFTs), a pathological hallmark in Alzheimer's disease
      (AD). A characteristic of AD tau is hyperphosphorylation with more than 40
      phosphorylation sites. Aggregates of hyperphosphorylated tau are also found in
      other neurodegenerative diseases which are collectively called tauopathies.
      Although a large number of studies have been performed on the phosphorylation of
      AD tau, it is not known if there is disease-specific phosphorylation among
      tauopathies. This is due to the lack of a proper method for analyzing tau
      phosphorylation in vivo. Most previous phosphorylation studies were conducted
      using a range of phosphorylation site-specific antibodies. These studies describe
      relative changes of different phosphorylation sites, however, it is hard to
      estimate total, absolute and collective changes in phosphorylation. To overcome
      these problems, we have recently applied the Phos-Tag technique to the analysis
      of tau phosphorylation in vitro and in vivo. This method separates tau into many
      bands during SDS-PAGE depending on its phosphorylation states, creating a bar
      code appearance. We propose calling this banding pattern of tau the "phospho-tau
      bar code." In this review article, we describe what is newly discovered regarding
      tau phosphorylation through the use of the Phos-Tag. We would like to propose its
      use for the postmortem diagnosis of tauopathy which is presently done by
      immunostaining diseased brains with anti-phospho-antibodies. While Phos-tag SDS
      PAGE, like other biochemical assays, will lose morphological information, it
      could provide other types of valuable information such as disease-specific
      phosphorylation.

PMID- 29467610
TI  - Open Science Meets Stem Cells: A New Drug Discovery Approach for
      Neurodegenerative Disorders.
AB  - Neurodegenerative diseases are a challenge for drug discovery, as the biological
      mechanisms are complex and poorly understood, with a paucity of models that
      faithfully recapitulate these disorders. Recent advances in stem cell technology
      have provided a paradigm shift, providing researchers with tools to generate
      human induced pluripotent stem cells (iPSCs) from patient cells. With the
      potential to generate any human cell type, we can now generate human neurons and
      develop "first-of-their-kind" disease-relevant assays for small molecule
      screening. Now that the tools are in place, it is imperative that we accelerate
      discoveries from the bench to the clinic. Using traditional closed-door research
      systems raises barriers to discovery, by restricting access to cells, data and
      other research findings. Thus, a new strategy is required, and the Montreal
      Neurological Institute (MNI) and its partners are piloting an "Open Science"
      model. One signature initiative will be that the MNI biorepository will curate
      and disseminate patient samples in a more accessible manner through open transfer
      agreements. This feeds into the MNI open drug discovery platform, focused on
      developing industry-standard assays with iPSC-derived neurons. All cell lines,
      reagents and assay findings developed in this open fashion will be made available
      to academia and industry. By removing the obstacles many universities and
      companies face in distributing patient samples and assay results, our goal is to
      accelerate translational medical research and the development of new therapies
      for devastating neurodegenerative disorders.

PMID- 29467612
TI  - Commentary: Sound-making actions lead to immediate plastic changes of
      neuromagnetic evoked responses and induced beta-band oscillations during
      perception.

PMID- 29467611
TI  - The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis.
AB  - The microbiota, the gut, and the brain communicate through the microbiota-gut
      brain axis in a bidirectional way that involves the autonomic nervous system. The
      vagus nerve (VN), the principal component of the parasympathetic nervous system,
      is a mixed nerve composed of 80% afferent and 20% efferent fibers. The VN,
      because of its role in interoceptive awareness, is able to sense the microbiota
      metabolites through its afferents, to transfer this gut information to the
      central nervous system where it is integrated in the central autonomic network,
      and then to generate an adapted or inappropriate response. A cholinergic anti
      inflammatory pathway has been described through VN's fibers, which is able to
      dampen peripheral inflammation and to decrease intestinal permeability, thus very
      probably modulating microbiota composition. Stress inhibits the VN and has
      deleterious effects on the gastrointestinal tract and on the microbiota, and is
      involved in the pathophysiology of gastrointestinal disorders such as irritable
      bowel syndrome (IBS) and inflammatory bowel disease (IBD) which are both
      characterized by a dysbiosis. A low vagal tone has been described in IBD and IBS
      patients thus favoring peripheral inflammation. Targeting the VN, for example
      through VN stimulation which has anti-inflammatory properties, would be of
      interest to restore homeostasis in the microbiota-gut-brain axis.

PMID- 29467613
TI  - Exercise-Mediated Neurogenesis in the Hippocampus via BDNF.
AB  - Exercise is known to have numerous neuroprotective and cognitive benefits,
      especially pertaining to memory and learning related processes. One potential
      link connecting them is exercise-mediated hippocampal neurogenesis, in which new
      neurons are generated and incorporated into hippocampal circuits. The present
      review synthesizes the extant literature detailing the relationship between
      exercise and hippocampal neurogenesis, and identifies a key molecule mediating
      this process, brain-derived neurotrophic factor (BDNF). As a member of the
      neurotrophin family, BDNF regulates many of the processes within neurogenesis,
      such as differentiation and survival. Although much more is known about the
      direct role that exercise and BDNF have on hippocampal neurogenesis in rodents,
      their corresponding cognitive benefits in humans will also be discussed.
      Specifically, what is known about exercise-mediated hippocampal neurogenesis will
      be presented as it relates to BDNF to highlight the critical role that it plays.
      Due to the inaccessibility of the human brain, much less is known about the role
      BDNF plays in human hippocampal neurogenesis. Limitations and future areas of
      research with regards to human neurogenesis will thus be discussed, including
      indirect measures of neurogenesis and single nucleotide polymorphisms within the
      BDNF gene.

PMID- 29467614
TI  - Safety and Efficacy of Scanning Ultrasound Treatment of Aged APP23 Mice.
AB  - Deposition of amyloid-beta (Abeta) peptide leads to amyloid plaques that together
      with tau deposits characterize the brains of patients with Alzheimer's disease
      (AD). In modeling this pathology, transgenic animals such as the APP23 strain,
      that expresses a mutant form of the amyloid precursor protein found in familial
      cases of AD, have been instrumental. In previous studies, we have shown that
      repeated treatments with ultrasound in a scanning mode (termed scanning
      ultrasound or SUS) were effective in removing Abeta and restoring memory
      functions, without the need for a therapeutic agent such as an Abeta antibody.
      Considering that age is the most important risk factor for AD, we extended this
      study in which the mice were only 12 months old at the time of treatment by
      assessing a cohort of 2 year-old mice. Interestingly, at this age, APP23 mice are
      characterized by cerebral amyloid angiopathy (CAA) and the presence of occasional
      microbleeds. We found that SUS in aged mice that have been exposed to four SUS
      sessions that were spread out over 8 weeks and analyzed 4 weeks later did not
      show evidence of increased CAA or microbleeds. Furthermore, amyloid was reduced
      as assessed by methoxy-XO4 fluorescence. In addition, plaque-associated microglia
      were more numerous in SUS treated mice. Together this adds to the notion that SUS
      may be a treatment modality for human neurodegenerative diseases.

PMID- 29467615
TI  - Decoding English Alphabet Letters Using EEG Phase Information.
AB  - Increasing evidence indicates that the phase pattern and power of the low
      frequency oscillations of brain electroencephalograms (EEG) contain significant
      information during the human cognition of sensory signals such as auditory and
      visual stimuli. Here, we investigate whether and how the letters of the alphabet
      can be directly decoded from EEG phase and power data. In addition, we
      investigate how different band oscillations contribute to the classification and
      determine the critical time periods. An English letter recognition task was
      assigned, and statistical analyses were conducted to decode the EEG signal
      corresponding to each letter visualized on a computer screen. We applied support
      vector machine (SVM) with gradient descent method to learn the potential features
      for classification. It was observed that the EEG phase signals have a higher
      decoding accuracy than the oscillation power information. Low-frequency theta and
      alpha oscillations have phase information with higher accuracy than do other
      bands. The decoding performance was best when the analysis period began from 180
      to 380 ms after stimulus presentation, especially in the lateral occipital and
      posterior temporal scalp regions (PO7 and PO8). These results may provide a new
      approach for brain-computer interface techniques (BCI) and may deepen our
      understanding of EEG oscillations in cognition.

PMID- 29467616
TI  - Molecular Characterization of GABA-A Receptor Subunit Diversity within Major
      Peripheral Organs and Their Plasticity in Response to Early Life Psychosocial
      Stress.
AB  - Gamma aminobutyric acid (GABA) subtype A receptors (GABAARs) are integral
      membrane ion channels composed of five individual proteins or subunits. Up to 19
      different GABAAR subunits (alpha1-6, beta1-3, gamma1-3, delta, epsilon, theta,
      pi, and rho1-3) have been identified, resulting in anatomically, physiologically,
      and pharmacologically distinct multiple receptor subtypes, and therefore GABA
      mediated inhibition, across the central nervous system (CNS). Additionally,
      GABAAR-modulating drugs are important tools in clinical medicine, although their
      use is limited by adverse effects. While significant advances have been made in
      terms of characterizing the GABAAR system within the brain, relatively less is
      known about the molecular phenotypes within the peripheral nervous system of
      major organ systems. This represents a potentially missed therapeutic opportunity
      in terms of utilizing or repurposing clinically available GABAAR drugs, as well
      as promising research compounds discarded due to their poor CNS penetrance, for
      the treatment of peripheral disorders. In addition, a broader understanding of
      the peripheral GABAAR subtype repertoires will contribute to the design of
      therapies which minimize peripheral side-effects when treating CNS disorders. We
      have recently provided a high resolution molecular and function characterization
      of the GABAARs within the enteric nervous system of the mouse colon. In this
      study, the aim was to determine the constituent GABAAR subunit expression
      profiles of the mouse bladder, heart, liver, kidney, lung, and stomach, using
      reverse transcription polymerase chain reaction and western blotting with brain
      as control. The data indicate that while some subunits are expressed widely
      across various organs (alpha3-5), others are restricted to individual organs
      (gamma2, only stomach). Furthermore, we demonstrate complex organ-specific
      developmental expression plasticity of the transporters which determine the
      chloride gradient within cells, and therefore whether GABAAR activation has a
      depolarizing or hyperpolarizing effect. Finally, we demonstrate that prior
      exposure to early life psychosocial stress induces significant changes in
      peripheral GABAAR subunit expression and chloride transporters, in an organ- and
      subunit-specific manner. Collectively, the data demonstrate the molecular
      diversity of the peripheral GABAAR system and how this changes dynamically in
      response to life experience. This provides a molecular platform for functional
      analyses of the GABA-GABAAR system in health, and in diseases affecting various
      peripheral organs.

PMID- 29467617
TI  - Quantitative Proteomics of Synaptosomal Fractions in a Rat Overexpressing Human
      DISC1 Gene Indicates Profound Synaptic Dysregulation in the Dorsal Striatum.
AB  - Disrupted-in-schizophrenia 1 (DISC1) is a key protein involved in behavioral
      processes and various mental disorders, including schizophrenia and major
      depression. A transgenic rat overexpressing non-mutant human DISC1, modeling
      aberrant proteostasis of the DISC1 protein, displays behavioral, biochemical and
      anatomical deficits consistent with aspects of mental disorders, including
      changes in the dorsal striatum, an anatomical region critical in the development
      of behavioral disorders. Herein, dorsal striatum of 10 transgenic DISC1 (tgDISC1)
      and 10 wild type (WT) littermate control rats was used for synaptosomal
      preparations and for performing liquid chromatography-tandem mass spectrometry
      (LC-MS)-based quantitative proteomics, using isobaric labeling (TMT10plex).
      Functional enrichment analysis was generated from proteins with level changes.
      The increase in DISC1 expression leads to changes in proteins and synaptic
      associated processes including membrane trafficking, ion transport, synaptic
      organization and neurodevelopment. Canonical pathway analysis assigned proteins
      with level changes to actin cytoskeleton, Galphaq, Rho family GTPase and Rho GDI,
      axonal guidance, ephrin receptor and dopamine-DARPP32 feedback in cAMP signaling.
      DISC1-regulated proteins proposed in the current study are also highly associated
      with neurodevelopmental and mental disorders. Bioinformatics analyses from the
      current study predicted that the following biological processes may be activated
      by overexpression of DISC1, i.e., regulation of cell quantities, neuronal and
      axonal extension and long term potentiation. Our findings demonstrate that the
      effects of overexpression of non-mutant DISC1 or its misassembly has profound
      consequences on protein networks essential for behavioral control. These results
      are also relevant for the interpretation of previous as well as for the design of
      future studies on DISC1.

PMID- 29467618
TI  - Reevaluation of FMR1 Hypermethylation Timing in Fragile X Syndrome.
AB  - Fragile X syndrome (FXS) is one of the most common heritable forms of cognitive
      impairment. It results from a fragile X mental retardation protein (FMRP) protein
      deficiency caused by a CGG repeat expansion in the 5'-UTR of the X-linked FMR1
      gene. Whereas in most individuals the number of CGGs is steady and ranges between
      5 and 44 units, in patients it becomes extensively unstable and expands to a
      length exceeding 200 repeats (full mutation). Interestingly, this disease is
      exclusively transmitted by mothers who carry a premutation allele (55-200 CGG
      repeats). When the CGGs reach the FM range, they trigger the spread of abnormal
      DNA methylation, which coincides with a switch from active to repressive histone
      modifications. This results in epigenetic gene silencing of FMR1 presumably by a
      multi-stage, developmentally regulated process. The timing of FMR1
      hypermethylation and transcription silencing is still hotly debated. There is
      evidence that hypermethylation varies considerably between and within the tissues
      of patients as well as during fetal development, thus supporting the view that
      FMR1 silencing is a post-zygotic event that is developmentally structured. On the
      other hand, it may be established in the female germ line and transmitted to the
      fetus as an integral part of the mutation. This short review summarizes the data
      collected to date concerning the timing of FMR1 epigenetic gene silencing and
      reassess the evidence in favor of the theory that gene inactivation takes place
      by a developmentally regulated process around the 10th week of gestation.

PMID- 29467619
TI  - Cannabidiol Regulates Long Term Potentiation Following Status Epilepticus:
      Mediation by Calcium Stores and Serotonin.
AB  - Epilepsy is a devastating disease, with cognitive and emotional consequences that
      are not curable. In recent years, it became apparent that cannabinoids help
      patients to cope with epilepsy. We have studied the effects of cannabidiol (CBD)
      on the ability to produce long term potentiation (LTP) in stratum radiatum of CA1
      region of the mouse hippocampus. Exposure to seizure-producing pilocarpine
      reduced the ability to generate LTP in the slice. Pre-exposure to CBD prevented
      this effect of pilocarpine. Furthermore, CBD caused a marked increase in ability
      to generate LTP, an effect that was blocked by calcium store antagonists as well
      as by a reduction in serotonin tone. Serotonin, possibly acting at a 5HT1A
      receptor, or fenfluramine (FFA), which causes release of serotonin from its
      native terminals, mimicked the effect of CBD. It is proposed that CBD enhances
      non-NMDA LTP in the slice by facilitating release of serotonin from terminals,
      consequently ameliorating the detrimental effects of pilocarpine.

PMID- 29467620
TI  - MiR-429 Regulated by Endothelial Monocyte Activating Polypeptide-II (EMAP-II)
      Influences Blood-Tumor Barrier Permeability by Inhibiting the Expressions of ZO
      1, Occludin and Claudin-5.
AB  - The blood-tumor barrier (BTB) hinders delivery of chemotherapeutic drugs to
      tumors in the brain; previous studies have shown that the BTB can be selectively
      opened by endothelial monocyte activating polypeptide-II (EMAP-II), but the
      specific mechanism involved remains elusive. In this study, we found that
      microRNA-429 (miR-429) expression in glioma vascular endothelial cells (GECs) was
      far lower than in human brain microvascular endothelial cells (ECs). miR-429 had
      lower expression in GECs and glioma tissues compared to ECs or normal tissues of
      the brain. Furthermore, miR-429 had lower expression in high grade glioma (HGG)
      than in low grade glioma (LGG). In in vitro BTB models, we also found that EMAP
      II significantly increased BTB permeability, decreased expression of ZO-1,
      occludin and claudin-5 in GECs, in a time- and dose-dependent manner. EMAP-II
      greatly increased miR-429 expression in GECs of the BTB models in vitro.
      Overexpression of miR-429 in GECs significantly decreased the transepithelial
      electric resistance (TEER) values in BTB models, and led to enhanced horseradish
      peroxidase (HRP) flux. Overexpression of miR-429 in GECs significantly decreased
      the expression of tight junction (TJ)-associated proteins (ZO-1, occludin and
      claudin-5), and decreased the distribution continuity. Silencing of miR-429 in
      GECs increased the expression of TJ-associated proteins and the distribution
      continuity. The dual-luciferase reporter assay revealed that ZO-1 and occludin
      were target genes of miR-429, and we demonstrated that miR-429 overexpression
      markedly down-regulated protein expression of p70S6K, as well as its
      phosphorylation levels. The dual-luciferase reporter assay also showed that
      p70S6K was a target gene of miR-429; miR-429 overexpression down-regulated
      expression and phosphorylation levels of p70S6K, and also decreased
      phosphorylation levels of S6 and increased BTB permeability. Conversely,
      silencing of miR-429 increased the expression and phosphorylation levels of
      p70S6K, and increased phosphorylation levels of S6, while decreasing BTB
      permeability. In conclusion, the results indicated that EMAP-II caused an
      increase in miR-429 expression that directly targeted TJ-associated proteins,
      which were negatively regulated; on the other hand, miR-429 down-regulated the
      expression of TJ-associated proteins by targeting p70S6K, also negatively
      regulated. As a result, the BTB permeability increased.

PMID- 29467621
TI  - Immunosignals of Oligodendrocyte Markers and Myelin-Associated Proteins Are
      Critically Affected after Experimental Stroke in Wild-Type and Alzheimer Modeling
      Mice of Different Ages.
AB  - Because stroke therapies are still limited and patients are often concerned by
      long-term sequelae with significant impairment of daily living, elaborated
      neuroprotective strategies are needed. During the last decades, research
      substantially improved the knowledge on cellular pathologies responsible for
      stroke-related tissue damage. In this context, the neurovascular unit (NVU)
      concept has been established, summarizing the affections of neurons, associated
      astrocytes and the vasculature. Although oligodendrocytes were already identified
      to play a major role in other brain pathologies, their role during stroke
      evolution and long-lasting tissue damage is poorly understood. This study aims to
      explore oligodendrocyte structures, i.e., oligodendrocytes and their myelin
      associated proteins, after experimental focal cerebral ischemia. For
      translational issues, different ages and genotypes including an Alzheimer-like
      background were considered to mimic potential co-morbidities. Three- and 12-month
      old wild-type and triple-transgenic mice were subjected to unilateral middle
      cerebral artery occlusion. Immunofluorescence labeling was performed on forebrain
      tissues affected by 24 h of ischemia to visualize the oligodendrocyte-specific
      protein (OSP), the myelin basic protein (MBP), and the neuron-glia antigen 2
      (NG2) with reference to the ischemic lesion. Subsequent analyses concomitantly
      detected the vasculature and the 2', 3'-cyclic nucleotide-3'-phosphodiesterase
      (CNPase) to consider the NVU concept and to explore the functional relevance of
      histochemical data on applied oligodendrocyte markers. While the immunosignal of
      NG2 was found to be nearly absent 24 h after ischemia onset, enhanced
      immunoreactivities for OSP and especially MBP were observed in close regional
      association to the vasculature. Added quantitative analyses based on inter
      hemispheric differences of MBP-immunoreactivity revealed a shell-like pattern
      with a significant increase directly in the ischemic core, followed by a gradual
      decline toward the striatum, the ischemic border zone and the lateral neocortex.
      This observation was consistent in subsequent analyses on the potential impact of
      age and genetic background. Furthermore, immunoreactivities for CNPase, MBP, and
      OSP were found to be simultaneously enhanced. In conclusion, this study provides
      evidence for a critical role of oligodendrocyte structures in the early phase
      after experimental stroke, strengthening their involvement in the ischemia
      affected NVU. Consequently, oligodendrocytes and their myelin-associated proteins
      may qualify as potential targets for neuroprotective and regenerative approaches
      in stroke.

PMID- 29467623
TI  - eIF4E Phosphorylation Influences Bdnf mRNA Translation in Mouse Dorsal Root
      Ganglion Neurons.
AB  - Plasticity in dorsal root ganglion (DRG) neurons that promotes pain requires
      activity-dependent mRNA translation. Protein synthesis inhibitors block the
      ability of many pain-promoting molecules to enhance excitability in DRG neurons
      and attenuate behavioral signs of pain plasticity. In line with this, we have
      recently shown that phosphorylation of the 5' cap-binding protein, eIF4E, plays a
      pivotal role in plasticity of DRG nociceptors in models of hyperalgesic priming.
      However, mRNA targets of eIF4E phosphorylation have not been elucidated in the
      DRG. Brain-derived neurotrophic factor (BDNF) signaling from nociceptors in the
      DRG to spinal dorsal horn neurons is an important mediator of hyperalgesic
      priming. Regulatory mechanisms that promote pain plasticity via controlling BDNF
      expression that is involved in promoting pain plasticity have not been
      identified. We show that phosphorylation of eIF4E is paramount for Bdnf mRNA
      translation in the DRG. Bdnf mRNA translation is reduced in mice lacking eIF4E
      phosphorylation (eIF4ES209A ) and pro-nociceptive factors fail to increase BDNF
      protein levels in the DRGs of these mice despite robust upregulation of Bdnf-201
      mRNA levels. Importantly, bypassing the DRG by giving intrathecal injection of
      BDNF in eIF4ES209A mice creates a strong hyperalgesic priming response that is
      normally absent or reduced in these mice. We conclude that eIF4E phosphorylation
      mediated translational control of BDNF expression is a key mechanism for
      nociceptor plasticity leading to hyperalgesic priming.

PMID- 29467624
TI  - Procedure for the Isolation of Endothelial Cells from Human Cerebral
      Arteriovenous Malformation (cAVM) Tissues.
AB  - In this study, we successfully established a stable method for the isolation of
      endothelial cells (ECs) from human cerebral arteriovenous malformation (cAVM)
      tissues. Despite human cAVM tissues having a minor population of ECs, they play
      an important role in the manifestation and development of cAVM as well as in
      hemorrhagic stroke and thrombogenesis. To characterize and understand the biology
      of ECs in human cAVM (cAVM-ECs), methods for the isolation and purification of
      these cells are necessary. We have developed this method to reliably obtain pure
      populations of ECs from cAVMs. To obtain pure cell populations, cAVM tissues were
      mechanically and enzymatically digested and the resulting single cAVM-ECs
      suspensions were then labeled with antibodies of specific cell antigens and
      selected by flow cytometry. Purified ECs were detected using specific makers of
      ECs by immunostaining and used to study different cellular mechanisms. Compared
      to the different methods of isolating ECs from tissues, we could isolate ECs from
      cAVMs confidently, and the numbers of cAVM-ECs harvested were almost similar to
      the amounts present in vessel components. In addition to optimizing the protocol
      for isolation of ECs from human cAVM tissues, the protocol could also be applied
      to isolate ECs from other human neurovascular-diseased tissues. Depending on the
      tissues, the whole procedure could be completed in about 20 days.

PMID- 29467622
TI  - Revisiting the Role of Clathrin-Mediated Endoytosis in Synaptic Vesicle
      Recycling.
AB  - Without robust mechanisms to efficiently form new synaptic vesicles (SVs), the
      tens to hundreds of SVs typically present at the neuronal synapse would be
      rapidly used up, even at modest levels of neuronal activity. SV recycling is thus
      critical for synaptic physiology and proper function of sensory and nervous
      systems. Yet, more than four decades after it was originally proposed that the
      SVs are formed and recycled locally at the presynaptic terminals, the mechanisms
      of endocytic processes at the synapse are heavily debated. Clathrin-mediated
      endocytosis, a type of endocytosis that capitalizes on the clathrin coat, a
      number of adaptor and accessory proteins, and the GTPase dynamin, is well
      understood, while the contributions of clathrin-independent fast endocytosis,
      kiss-and-run, bulk endocytosis and ultrafast endocytosis are still being
      evaluated. This review article revisits and summarizes the current knowledge on
      the SV reformation with a focus on clathrin-mediated endocytosis, and it
      discusses the modes of SV formation from endosome-like structures at the synapse.
      Given the importance of this topic, future advances in this active field are
      expected to contribute to better comprehension of neurotransmission, and to have
      general implications for neuroscience and medicine.

PMID- 29467626
TI  - The Fly Sensitizing Pigment Enhances UV Spectral Sensitivity While Preventing
      Polarization-Induced Artifacts.
AB  - Microvillar photoreceptors are intrinsically capable of detecting the orientation
      of e-vector of linearly polarized light. They provide most invertebrates with an
      additional sensory channel to detect important features of their visual
      environment. However, polarization sensitivity (PS) of photoreceptors may lead to
      the detection of polarization-induced false colors and intensity contrasts. Most
      insect photoreceptors are thus adapted to have minimal PS. Flies have twisted
      rhabdomeres with microvilli rotated along the length of the ommatidia to reduce
      PS. The additional UV-absorbing sensitizing pigment on their opsin minimizes PS
      in the ultraviolet. We recorded voltage from Drosophila photoreceptors R1-6 to
      measure the spectral dependence of PS and found that PS in the UV is invariably
      negligible but can be substantial above 400 nm. Using modeling, we demonstrate
      that in R1-6 without the sensitizing pigment, PS in the UV (PS UV ) would exceed
      PS in the visible part of the spectrum (PS VIS ) by a factor PS UV /PS VIS = 1.2
      1.8, as lower absorption of Rh1 rhodopsin reduces self-screening. We use
      polarimetric imaging of objects relevant to fly polarization vision to show that
      their degree of polarization outdoors is highest in the short-wavelength part of
      the spectrum. Thus, under natural illumination, the sensitizing pigment in R1-6
      renders even those cells with high PS in the visible part unsuitable for proper
      polarization vision. We assume that fly ventral polarization vision can be
      mediated by R7 alone, with R1-6 serving as an unpolarized reference channel.

PMID- 29467625
TI  - Effect of Vitamin D in HN9.10e Embryonic Hippocampal Cells and in Hippocampus
      from MPTP-Induced Parkinson's Disease Mouse Model.
AB  - It has long been proven that neurogenesis continues in the adult brains of
      mammals in the dentatus gyrus of the hippocampus due to the presence of neural
      stem cells. Although a large number of studies have been carried out to highlight
      the localization of vitamin D receptor in hippocampus, the expression of vitamin
      D receptor in neurogenic dentatus gyrus of hippocampus in Parkinson's disease
      (PD) and the molecular mechanisms triggered by vitamin D underlying the
      production of differentiated neurons from embryonic cells remain unknown. Thus,
      we performed a preclinical in vivo study by inducing PD in mice with MPTP and
      showed a reduction of glial fibrillary acidic protein (GFAP) and vitamin D
      receptor in the dentatus gyrus of hippocampus. Then, we performed an in vitro
      study by inducing embryonic hippocampal cell differentiation with vitamin D.
      Interestingly, vitamin D stimulates the expression of its receptor. Vitamin D
      receptor is a transcription factor that probably is responsible for the
      upregulation of microtubule associated protein 2 and neurofilament heavy
      polypeptide genes. The latter increases heavy neurofilament protein expression,
      essential for neurofilament growth. Notably N-cadherin, implicated in activity
      for dendritic outgrowth, is upregulated by vitamin D.

PMID- 29467628
TI  - Anatomical Evidence for a Direct Projection from Purkinje Cells in the Mouse
      Cerebellar Vermis to Medial Parabrachial Nucleus.
AB  - Cerebellar malformations cause changes to the sleep-wake cycle, resulting in
      sleep disturbance. However, it is unclear how the cerebellum contributes to the
      sleep-wake cycle. To examine the neural connections between the cerebellum and
      the nuclei involved in the sleep-wake cycle, we investigated the axonal
      projections of Purkinje cells in the mouse posterior vermis by using an adeno
      associated virus (AAV) vector (serotype rh10) as an anterograde tracer. When an
      AAV vector expressing humanized renilla green fluorescent protein was injected
      into the cerebellar lobule IX, hrGFP and synaptophysin double-positive axonal
      terminals were observed in the region of medial parabrachial nucleus (MPB). The
      MPB is involved in the phase transition from rapid eye movement (REM) sleep to
      Non-REM sleep and vice versa, and the cardiovascular and respiratory responses.
      The hrGFP-positive axons from lobule IX went through the ventral spinocerebellar
      tract and finally reached the MPB. By contrast, when the AAV vector was injected
      into cerebellar lobule VI, no hrGFP-positive axons were observed in the MPB. To
      examine neurons projecting to the MPB, we unilaterally injected Fast Blue and AAV
      vector (retrograde serotype, rAAV2-retro) as retrograde tracers into the MPB. The
      cerebellar Purkinje cells in lobules VIII-X on the ipsilateral side of the Fast
      Blue-injected MPB were retrogradely labeled by Fast Blue and AAV vector
      (retrograde serotype), but no retrograde-labeled Purkinje cells were observed in
      lobules VI-VII and the cerebellar hemispheres. These results indicated that
      Purkinje cells in lobules VIII-X directly project their axons to the ipsilateral
      MPB but not lobules VI-VII. The direct connection between lobules VIII-X and the
      MPB suggests that the cerebellum participates in the neural network controlling
      the sleep-wake cycle, and cardiovascular and respiratory responses, by modulating
      the physiological function of the MPB.

PMID- 29467627
TI  - Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales
      Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic
      Effects and Predict the Role of Kv4.2.
AB  - The basal ganglia are involved in the motivational and habitual control of motor
      and cognitive behaviors. Striatum, the largest basal ganglia input stage,
      integrates cortical and thalamic inputs in functionally segregated cortico-basal
      ganglia-thalamic loops, and in addition the basal ganglia output nuclei control
      targets in the brainstem. Striatal function depends on the balance between the
      direct pathway medium spiny neurons (D1-MSNs) that express D1 dopamine receptors
      and the indirect pathway MSNs that express D2 dopamine receptors. The striatal
      microstructure is also divided into striosomes and matrix compartments, based on
      the differential expression of several proteins. Dopaminergic afferents from the
      midbrain and local cholinergic interneurons play crucial roles for basal ganglia
      function, and striatal signaling via the striosomes in turn regulates the
      midbrain dopaminergic system directly and via the lateral habenula. Consequently,
      abnormal functions of the basal ganglia neuromodulatory system underlie many
      neurological and psychiatric disorders. Neuromodulation acts on multiple
      structural levels, ranging from the subcellular level to behavior, both in health
      and disease. For example, neuromodulation affects membrane excitability and
      controls synaptic plasticity and thus learning in the basal ganglia. However, it
      is not clear on what time scales these different effects are implemented.
      Phosphorylation of ion channels and the resulting membrane effects are typically
      studied over minutes while it has been shown that neuromodulation can affect
      behavior within a few hundred milliseconds. So how do these seemingly
      contradictory effects fit together? Here we first briefly review neuromodulation
      of the basal ganglia, with a focus on dopamine. We furthermore use biophysically
      detailed multi-compartmental models to integrate experimental data regarding
      dopaminergic effects on individual membrane conductances with the aim to explain
      the resulting cellular level dopaminergic effects. In particular we predict
      dopaminergic effects on Kv4.2 in D1-MSNs. Finally, we also explore dynamical
      aspects of the onset of neuromodulation effects in multi-scale computational
      models combining biochemical signaling cascades and multi-compartmental neuron
      models.

PMID- 29467629
TI  - Orientation-Selective Retinal Circuits in Vertebrates.
AB  - Visual information is already processed in the retina before it is transmitted to
      higher visual centers in the brain. This includes the extraction of salient
      features from visual scenes, such as motion directionality or contrast, through
      neurons belonging to distinct neural circuits. Some retinal neurons are tuned to
      the orientation of elongated visual stimuli. Such 'orientation-selective' neurons
      are present in the retinae of most, if not all, vertebrate species analyzed to
      date, with species-specific differences in frequency and degree of tuning. In
      some cases, orientation-selective neurons have very stereotyped functional and
      morphological properties suggesting that they represent distinct cell types. In
      this review, we describe the retinal cell types underlying orientation
      selectivity found in various vertebrate species, and highlight their
      commonalities and differences. In addition, we discuss recent studies that
      revealed the cellular, synaptic and circuit mechanisms at the basis of retinal
      orientation selectivity. Finally, we outline the significance of these findings
      in shaping our current understanding of how this fundamental neural computation
      is implemented in the visual systems of vertebrates.

PMID- 29467630
TI  - Neural, Cellular and Molecular Mechanisms of Active Forgetting.
AB  - The neurobiology of memory formation attracts much attention in the last five
      decades. Conversely, the rules that govern and the mechanisms underlying
      forgetting are less understood. In addition to retroactive interference,
      retrieval-induced forgetting and passive decay of time, it has been recently
      demonstrated that the nervous system has a diversity of active and inherent
      processes involved in forgetting. In Drosophila, some operate mainly at an early
      stage of memory formation and involves dopamine (DA) neurons, specific
      postsynaptic DA receptor subtypes, Rac1 activation and induces rapid active
      forgetting. In mammals, others regulate forgetting and persistence of seemingly
      consolidated memories and implicate the activity of DA receptor subtypes and AMPA
      receptors in the hippocampus (HP) and related structures to activate parallel
      signaling pathways controlling active time-dependent forgetting. Most of them may
      involve plastic changes in synaptic and extrasynaptic receptors including
      specific removal of GluA2 AMPA receptors. Forgetting at longer timescales might
      also include changes in adult neurogenesis in the dentate gyrus (DG) of the HP.
      Therefore, based on relevance or value considerations neuronal circuits may
      regulate in a time-dependent manner what is formed, stored, and maintained and
      what is forgotten.

PMID- 29467631
TI  - Neural Temporal Dynamics of Social Exclusion Elicited by Averted Gaze: An Event
      Related Potentials Study.
AB  - Eye gaze plays a fundamental role in social communication. The averted eye gaze
      during social interaction, as the most common form of silent treatment, conveys a
      signal of social exclusion. In the present study, we examined the time course of
      brain response to social exclusion by using a modified version of Eye-gaze
      paradigm. The event-related potentials (ERPs) data and the subjective rating data
      showed that the frontocentral P200 was positively correlated with negative mood
      of excluded events, whereas, the centroparietal late positive potential (LPP) was
      positively correlated with the perceived ostracism intensity. Both the P200 and
      LPP were more positive-going for excluded events than for included events. These
      findings suggest that brain responses sensitive to social exclusion can be
      divided into the early affective processing stage, linking to the early pre
      cognitive warning system; and the late higher-order processes stage, demanding
      attentional resources for elaborate stimuli evaluation and categorization
      generally not under specific situation.

PMID- 29467632
TI  - Dissociating Explicit and Implicit Timing in Parkinson's Disease Patients:
      Evidence from Bisection and Foreperiod Tasks.
AB  - A consistent body of literature reported that Parkinson's disease (PD) is marked
      by severe deficits in temporal processing. However, the exact nature of timing
      problems in PD patients is still elusive. In particular, what remains unclear is
      whether the temporal dysfunction observed in PD patients regards explicit and/or
      implicit timing. Explicit timing tasks require participants to attend to the
      duration of the stimulus, whereas in implicit timing tasks no explicit
      instruction to process time is received but time still affects performance. In
      the present study, we investigated temporal ability in PD by comparing 20 PD
      participants and 20 control participants in both explicit and implicit timing
      tasks. Specifically, we used a time bisection task to investigate explicit timing
      and a foreperiod task for implicit timing. Moreover, this is the first study
      investigating sequential effects in PD participants. Results showed preserved
      temporal ability in PD participants in the implicit timing task only (i.e.,
      normal foreperiod and sequential effects). By contrast, PD participants failed in
      the explicit timing task as they displayed shorter perceived durations and higher
      variability compared to controls. Overall, the dissociation reported here
      supports the idea that timing can be differentiated according to whether it is
      explicitly or implicitly processed, and that PD participants are selectively
      impaired in the explicit processing of time.

PMID- 29467633
TI  - Closed-Loop Targeted Memory Reactivation during Sleep Improves Spatial
      Navigation.
AB  - Sounds associated with newly learned information that are replayed during non
      rapid eye movement (NREM) sleep can improve recall in simple tasks. The mechanism
      for this improvement is presumed to be reactivation of the newly learned memory
      during sleep when consolidation takes place. We have developed an EEG-based
      closed-loop system to precisely deliver sensory stimulation at the time of down
      state to up-state transitions during NREM sleep. Here, we demonstrate that
      applying this technology to participants performing a realistic navigation task
      in virtual reality results in a significant improvement in navigation efficiency
      after sleep that is accompanied by increases in the spectral power especially in
      the fast (12-15 Hz) sleep spindle band. Our results show promise for the
      application of sleep-based interventions to drive improvement in real-world
      tasks.

PMID- 29467635
TI  - Oscillatory Brain Responses Reflect Anticipation during Comprehension of Speech
      Acts in Spoken Dialog.
AB  - Everyday conversation requires listeners to quickly recognize verbal actions, so
      called speech acts, from the underspecified linguistic code and prepare a
      relevant response within the tight time constraints of turn-taking. The goal of
      this study was to determine the time-course of speech act recognition by
      investigating oscillatory EEG activity during comprehension of spoken dialog.
      Participants listened to short, spoken dialogs with target utterances that
      delivered three distinct speech acts (Answers, Declinations, Pre-offers). The
      targets were identical across conditions at lexico-syntactic and
      phonetic/prosodic levels but differed in the pragmatic interpretation of the
      speech act performed. Speech act comprehension was associated with reduced power
      in the alpha/beta bands just prior to Declination speech acts, relative to
      Answers and Pre-offers. In addition, we observed reduced power in the theta band
      during the beginning of Declinations, relative to Answers. Based on the role of
      alpha and beta desynchronization in anticipatory processes, the results are taken
      to indicate that anticipation plays a role in speech act recognition.
      Anticipation of speech acts could be critical for efficient turn-taking, allowing
      interactants to quickly recognize speech acts and respond within the tight time
      frame characteristic of conversation. The results show that anticipatory
      processes can be triggered by the characteristics of the interaction, including
      the speech act type.

PMID- 29467636
TI  - Increased Posterior Insula-Sensorimotor Connectivity Is Associated with Cognitive
      Function in Healthy Participants with Sleep Complaints.
AB  - Insomnia is characterized by sensory hypersensitivity and cognitive impairments.
      Recent work has identified the insula as a central brain region involved in both
      bottom-up gating of sensory information and top-down cognitive control. However,
      the specific relationships between insular subregion connectivity and emotional
      and cognitive functions remain unclear. In this study, resting-state functional
      magnetic resonance imaging data were obtained from 25 healthy participants with
      sleep complaints (HPS) and 25 age-, gender- and educational level-matched healthy
      participants without insomnia complaints (HP). We performed insular subregion
      (ventral anterior, dorsal anterior and posterior) functional connectivity (FC)
      analyses, and cognitive function was measured with several validated test
      procedures (e.g., the Wisconsin Card Sorting Test [WCST], Continuous Performance
      Test [CPT] and Trail making Test [TMT]). There were no significant differences
      between the two groups for WCST, CPT and TMT scores. The HPS group showed
      enhanced connectivity from the right posterior insula (R-PI) to the left
      postcentral gyrus (L-postCG) compared to HP group. WCST random errors (RE), sleep
      disturbance scores and HAMA scores correlated with this connectivity measurement
      in both HP and HPS groups. Our results provide direct evidence that the posterior
      insula (PI) synchronizes with sensorimotor areas to detect homeostatic changes
      and suggest that alteration of the latter is related to executive dysfunction in
      subjects with insomnia.

PMID- 29467634
TI  - EEG-Informed fMRI: A Review of Data Analysis Methods.
AB  - The simultaneous acquisition of electroencephalography (EEG) with functional
      magnetic resonance imaging (fMRI) is a very promising non-invasive technique for
      the study of human brain function. Despite continuous improvements, it remains a
      challenging technique, and a standard methodology for data analysis is yet to be
      established. Here we review the methodologies that are currently available to
      address the challenges at each step of the data analysis pipeline. We start by
      surveying methods for pre-processing both EEG and fMRI data. On the EEG side, we
      focus on the correction for several MR-induced artifacts, particularly the
      gradient and pulse artifacts, as well as other sources of EEG artifacts. On the
      fMRI side, we consider image artifacts induced by the presence of EEG hardware
      inside the MR scanner, and the contamination of the fMRI signal by physiological
      noise of non-neuronal origin, including a review of several approaches to model
      and remove it. We then provide an overview of the approaches specifically
      employed for the integration of EEG and fMRI when using EEG to predict the blood
      oxygenation level dependent (BOLD) fMRI signal, the so-called EEG-informed fMRI
      integration strategy, the most commonly used strategy in EEG-fMRI research.
      Finally, we systematically review methods used for the extraction of EEG features
      reflecting neuronal phenomena of interest.

PMID- 29467638
TI  - A Reinforcement-Based Learning Paradigm Increases Anatomical Learning and
      Retention-A Neuroeducation Study.
AB  - In anatomy education, a key hurdle to engaging in higher-level discussion in the
      classroom is recognizing and understanding the extensive terminology used to
      identify and describe anatomical structures. Given the time-limited classroom
      environment, seeking methods to impart this foundational knowledge to students in
      an efficient manner is essential. Just-in-Time Teaching (JiTT) methods
      incorporate pre-class exercises (typically online) meant to establish
      foundational knowledge in novice learners so subsequent instructor-led sessions
      can focus on deeper, more complex concepts. Determining how best do we design and
      assess pre-class exercises requires a detailed examination of learning and
      retention in an applied educational context. Here we used electroencephalography
      (EEG) as a quantitative dependent variable to track learning and examine the
      efficacy of JiTT activities to teach anatomy. Specifically, we examined changes
      in the amplitude of the N250 and reward positivity event-related brain potential
      (ERP) components alongside behavioral performance as novice students participated
      in a series of computerized reinforcement-based learning modules to teach
      neuroanatomical structures. We found that as students learned to identify
      anatomical structures, the amplitude of the N250 increased and reward positivity
      amplitude decreased in response to positive feedback. Both on a retention and
      transfer exercise when learners successfully remembered and translated their
      knowledge to novel images, the amplitude of the reward positivity remained
      decreased compared to early learning. Our findings suggest ERPs can be used as a
      tool to track learning, retention, and transfer of knowledge and that employing
      the reinforcement learning paradigm is an effective educational approach for
      developing anatomical expertise.

PMID- 29467637
TI  - Anterior Temporal Lobe Morphometry Predicts Categorization Ability.
AB  - Categorization is the mental operation by which the brain classifies objects and
      events. It is classically assessed using semantic and non-semantic matching or
      sorting tasks. These tasks show a high variability in performance across healthy
      controls and the cerebral bases supporting this variability remain unknown. In
      this study we performed a voxel-based morphometry study to explore the
      relationships between semantic and shape categorization tasks and brain
      morphometric differences in 50 controls. We found significant correlation between
      categorization performance and the volume of the gray matter in the right
      anterior middle and inferior temporal gyri. Semantic categorization tasks were
      associated with more rostral temporal regions than shape categorization tasks. A
      significant relationship was also shown between white matter volume in the right
      temporal lobe and performance in the semantic tasks. Tractography revealed that
      this white matter region involved several projection and association fibers,
      including the arcuate fasciculus, inferior fronto-occipital fasciculus, uncinate
      fasciculus, and inferior longitudinal fasciculus. These results suggest that
      categorization abilities are supported by the anterior portion of the right
      temporal lobe and its interaction with other areas.

PMID- 29467639
TI  - Editorial: Brain Oscillations in Human Communication.

PMID- 29467640
TI  - Alterations of Resting-State Static and Dynamic Functional Connectivity of the
      Dorsolateral Prefrontal Cortex in Subjects with Internet Gaming Disorder.
AB  - Internet gaming disorder (IGD), a major behavior disorder, has gained increasing
      attention. Recent studies indicate altered resting-state static functional
      connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC) in subjects with
      IGD. Whereas static FC often provides information on functional changes in
      subjects with IGD, investigations of temporal changes in FC between the DLPFC and
      the other brain regions may shed light on the dynamic characteristics of brain
      function associated with IGD. Thirty subjects with IGD and 30 healthy controls
      (HCs) matched for age, gender and education status were recruited. Using the
      bilateral DLPFC as seeds, static FC and dynamic FC maps were calculated and
      compared between groups. Correlations between alterations in static FC and
      dynamic FC and clinical variables were also investigated within the IGD group.
      The IGD group showed significantly lower static FC between the right DLPFC and
      the left rolandic operculum while higher static FC between the right DLPFC and
      the left pars triangularis when compared to HCs. The IGD group also had
      significantly decreased dynamic FC between the right DLPFC and the left insula,
      right putamen and left precentral gyrus, and increased dynamic FC in the left
      precuneus. Moreover, the dynamic FC between the right DLPFC and the left insula
      was negatively correlated with the severity of IGD. Dynamic FC can be used as a
      powerful supplement to static FC, helping us obtain a more comprehensive
      understanding of large-scale brain network activity in IGD and put forward new
      ideas for behavioral intervention therapy for it.

PMID- 29467641
TI  - Propensity for Bistability of Bursting and Silence in the Leech Heart
      Interneuron.
AB  - The coexistence of neuronal activity regimes has been reported under normal and
      pathological conditions. Such multistability could enhance the flexibility of the
      nervous system and has many implications for motor control, memory, and decision
      making. Multistability is commonly promoted by neuromodulation targeting specific
      membrane ionic currents. Here, we investigated how modulation of different ionic
      currents could affect the neuronal propensity for bistability. We considered a
      leech heart interneuron model. It exhibits bistability of bursting and silence in
      a narrow range of the leak current parameters, conductance (gleak ) and reversal
      potential (Eleak ). We assessed the propensity for bistability of the model by
      using bifurcation diagrams. On the diagram (gleak , Eleak ), we mapped bursting
      and silent regimes. For the canonical value of Eleak we determined the range of
      gleak which supported the bistability. We use this range as an index of
      propensity for bistability. We investigated how this index was affected by
      alterations of ionic currents. We systematically changed their conductances, one
      at a time, and built corresponding bifurcation diagrams in parameter planes of
      the maximal conductance of a given current and the leak conductance. We found
      that conductance of only one current substantially affected the index of
      propensity; the increase of the maximal conductance of the hyperpolarization
      activated cationic current increased the propensity index. The second conductance
      with the strongest effect was the conductance of the low-threshold fast Ca2+
      current; its reduction increased the propensity index although the effect was
      about two times smaller in magnitude. Analyzing the model with both changes
      applied simultaneously, we found that the diagram (gleak , Eleak ) showed a
      progressively expanded area of bistability of bursting and silence.

PMID- 29467642
TI  - Subcritical Hopf Bifurcation and Stochastic Resonance of Electrical Activities in
      Neuron under Electromagnetic Induction.
AB  - The FitzHugh-Nagumo model is improved to consider the effect of the
      electromagnetic induction on single neuron. On the basis of investigating the
      Hopf bifurcation behavior of the improved model, stochastic resonance in the
      stochastic version is captured near the bifurcation point. It is revealed that a
      weak harmonic oscillation in the electromagnetic disturbance can be amplified
      through stochastic resonance, and it is the cooperative effect of random
      transition between the resting state and the large amplitude oscillating state
      that results in the resonant phenomenon. Using the noise dependence of the mean
      of interburst intervals, we essentially suggest a biologically feasible clue for
      detecting weak signal by means of neuron model with subcritical Hopf bifurcation.
      These observations should be helpful in understanding the influence of the
      magnetic field to neural electrical activity.

PMID- 29467643
TI  - Simultaneous Estimation of Low- and High-Order Functional Connectivity for
      Identifying Mild Cognitive Impairment.
AB  - Functional connectivity (FC) network has been becoming an increasingly useful
      tool for understanding the cerebral working mechanism and mining sensitive
      biomarkers for neural/mental disease diagnosis. Currently, Pearson's Correlation
      (PC) is the simplest and most commonly used scheme in FC estimation. Despite its
      empirical effectiveness, PC only encodes the low-order (i.e., second-order)
      statistics by calculating the pairwise correlations between network nodes (brain
      regions), which fails to capture the high-order information involved in FC (e.g.,
      the correlations among different edges in a network). To address this issue, we
      propose a novel FC estimation method based on Matrix Variate Normal Distribution
      (MVND), which can capture both low- and high-order correlations simultaneously
      with a clear mathematical interpretability. Specifically, we first generate a set
      of BOLD subseries by the sliding window scheme, and for each subseries we
      construct a temporal FC network by PC. Then, we employ the constructed FC
      networks as samples to estimate the final low- and high-order FC networks by
      maximizing the likelihood of MVND. To illustrate the effectiveness of the
      proposed method, we conduct experiments to identify subjects with Mild Cognitive
      Impairment (MCI) from Normal Controls (NCs). Experimental results show that the
      fusion of low- and high-order FCs can generally help to improve the final
      classification performance, even though the high-order FC may contain less
      discriminative information than its low-order counterpart. Importantly, the
      proposed method for simultaneous estimation of low- and high-order FCs can
      achieve better classification performance than the two baseline methods, i.e.,
      the original PC method and a recent high-order FC estimation method.

PMID- 29467644
TI  - Use of Peptides for the Management of Alzheimer's Disease: Diagnosis and
      Inhibition.
AB  - Alzheimer's disease (AD) is a form of dementia and the most common progressive
      neurodegenerative disease (ND). The targeting of amyloid-beta (Abeta) aggregation
      is one of the most widely used strategies to manage AD, and efforts are being
      made globally to develop peptide-based compounds for the early diagnosis and
      treatment of AD. Here, we briefly discuss the use of peptide-based compounds for
      the early diagnosis and treatment of AD and the use of peptide-based inhibitors
      targeting various Abeta aggregation checkpoints. In addition, we briefly discuss
      recent applications of peptide-based inhibitors against various AD targets
      including amyloid beta, beta-site amyloid precursor protein cleaving enzyme 1
      (BACE1), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), tyrosine phosphatase
      (TP) and potassium channel KV1.3.

PMID- 29467645
TI  - Plasma Exosomal miRNA-122-5p and miR-300-3p as Potential Markers for Transient
      Ischaemic Attack in Rats.
AB  - Background: Differentiation of transient ischaemic attack (TIA) from ischaemic
      stroke within the thrombolysis time window is difficult. Although TIA may be
      diagnosed within this window, the latest imaging technologies are complex and
      costly. Serum markers, which are non-invasive, rapid and economic, are used for
      diagnosis and prognosis of various diseases. Exosome-derived miRNA markers for
      TIA are unknown. Methods: We examined focal brain ischaemia produced by occlusion
      of the middle cerebral artery (MCAo) for 5 min, 10 min, and 2 h in rats. Exosomal
      miRNAs with consistent trends in cerebrospinal fluid (CSF) and plasma were
      identified by deep sequencing and quantitative real-time polymerase chain
      reaction (qRT-PCR). The areas under the curve (AUC) of the receiver operating
      characteristic (ROC) curve were used to evaluate the diagnostic accuracy of these
      miRNAs for TIA in rats. Results: Rno-miR-122-5p and rno-miR-300-3p were selected.
      Plasma exosomal rno-miR-122-5p was significantly downregulated in 10 min
      ischaemic rats compared with control and 5 min plasma. Plasma exosomal rno-miR
      300-3p was significantly upregulated in 5 min ischaemic rats compared with
      control, 10 min and 2 h rats. Plasma and CSF levels of these miRNAs were
      correlated. ROC analysis showed high AUC values for rno-miR-122-5p (0.960) and
      rno-miR-300-3p (0.970) in the 10 and 5 min rats, respectively, compared with
      controls. Conclusions: Plasma exosomal rno-miR-122-5p and rno-miR-300-3p may be
      blood-based TIA biomarkers.

PMID- 29467647
TI  - Identification of a Novel Hemizygous SQSTM1 Nonsense Mutation in Atypical
      Behavioral Variant Frontotemporal Dementia.
AB  - Frontotemporal dementia includes a large spectrum of neurodegenerative disorders.
      SQSTM1, coding for p62 protein, plays a vital role in the pathogenesis of FTD.
      Here, we report a case of a female patient with SQSTM1 mutation S224X, who was 59
      years old when she initially exhibited memory decline, mild personality changes,
      and subtle atrophy of frontal/temporal lobes in magnetic resonance imaging (MRI).
      Genetic testing revealed a nonsense mutation of the SQSTM1 gene (S224X),
      resulting in premature termination of protein synthesis and a predicted truncated
      protein 217 amino acids shorter than the normal protein. Moreover, neither intact
      nor truncated SQSTM1 proteins was detectable in SQSTM1 S224X mutant
      overexpressing HEK-293T cells. We assayed for SQSTM1 cDNA in samples from the
      patient's peripheral leucocytes, and did not detect its mutation. The test of
      quantitative PCR showed significant decreased level of SQSTM1 mRNA from
      peripheral leucocytes of the patient compared to five dementia controls. Our
      results identify a novel pathogenic SQSTM1 S224X mutation in an atypical FTD
      patient accompanied with loss of SQSTM1/p62 protein expression probably due to
      SQSTM1 gene haploinsufficiency.

PMID- 29467646
TI  - Age-Dependent Modulations of Resting State Connectivity Following Motor Practice.
AB  - Recent work in young adults has demonstrated that motor learning can modulate
      resting state functional connectivity. However, evidence for older adults is
      scarce. Here, we investigated whether learning a bimanual tracking task modulates
      resting state functional connectivity of both inter- and intra-hemispheric
      regions differentially in young and older individuals, and whether this has
      behavioral relevance. Both age groups learned a set of complex bimanual tracking
      task variants over a 2-week training period. Resting-state and task-related
      functional magnetic resonance imaging scans were collected before and after
      training. Our analyses revealed that both young and older adults reached
      considerable performance gains. Older adults even obtained larger training
      induced improvements relative to baseline, but their overall performance levels
      were lower than in young adults. Short-term practice resulted in a modulation of
      resting state functional connectivity, leading to connectivity increases in young
      adults, but connectivity decreases in older adults. This pattern of age
      differences occurred for both inter- and intra-hemispheric connections related to
      the motor network. Additionally, long-term training-induced increases were
      observed in intra-hemispheric connectivity in the right hemisphere across both
      age groups. Overall, at the individual level, the long-term changes in inter
      hemispheric connectivity correlated with training-induced motor improvement. Our
      findings confirm that short-term task practice shapes spontaneous brain activity
      differentially in young and older individuals. Importantly, the association
      between changes in resting state functional connectivity and improvements in
      motor performance at the individual level may be indicative of how training
      shapes the short-term functional reorganization of the resting state motor
      network for improvement of behavioral performance.

PMID- 29467649
TI  - Tolerance and Tachyphylaxis to Head Twitches Induced by the 5-HT2A Agonist 25CN
      NBOH in Mice.
AB  - The serotonin (5-HT) 2A receptor is the primary molecular target of serotonergic
      hallucinogens, which trigger large-scale perturbations of the cortex. Our
      understanding of how 5-HT2A activation may cause the effects of hallucinogens has
      been hampered by the receptor unselectivity of most of the drugs of this class.
      Here we used 25CN-NBOH (N-(2-hydroxybenzyl)-2,5-dimethoxy-4
      cyanophenylethylamine), a newly developed selective 5-HT2A agonist, and tested it
      with regard to the head-twitch-response (HTR) model of 5-HT2A activity and
      effects on locomotion. 25CN-NBOH evoked HTRs with an inverted u-shape-like dose
      response curve and highest efficacy at 1.5 mg/kg, i.p. HTR occurrence peaked
      within 5 min after agonist injection, and exponentially decreased to half-maximal
      frequency at ~11 min. Thorough habituation to the experimental procedures
      (including handling, saline injection, and exposure to the observational boxes 1
      day before the experiment) facilitated the animals' response to 25CN-NBOH. 25CN
      NBOH (1.5 mg/kg, i.p.) induced HTRs were blocked by the 5-HT2A antagonist
      ketanserin (0.75 mg/kg, 30 min pre), but not by the 5-HT2C antagonist SB-242084
      (0.5 mg/kg, i.p., 30 min pre). SB-242084 instead slightly increased the number of
      HTRs occurring at a 3.0-mg/kg dose of the agonist. Apart from HTR induction, 25CN
      NBOH also modestly increased locomotor activity of the mice. Repeated once-per
      day injections (1.5 mg/kg, i.p.) led to reduced occurrence of 25CN-NBOH induced
      HTRs. This intermediate tolerance was augmented when a second (higher) dose of
      the drug (3.0 mg/kg) was interspersed. Short-interval tolerance (i.e.,
      tachyphylaxis) was observed when the drug was injected twice at intervals of 1.0
      and 1.5 h at either dose tested (1.5 mg/kg and 0.75 mg/kg, respectively).
      Inducing ketanserin-sensitive HTRs, which are dependent on environmental valences
      and which show signs of tachyphylaxis and tolerance, 25CN-NBOH shares striking
      features common to serotonergic hallucinogens. Given its distinct in vitro
      selectivity for 5-HT2A over non5-HT2 receptors and its behavioral dynamics, 25CN
      NBOH appears to be a powerful tool for dissection of receptor-specific cortical
      circuit dynamics, including 5-HT2A related psychoactivity.

PMID- 29467650
TI  - Additive Dose Response Models: Explicit Formulation and the Loewe Additivity
      Consistency Condition.
AB  - High-throughput techniques allow for massive screening of drug combinations. To
      find combinations that exhibit an interaction effect, one filters for promising
      compound combinations by comparing to a response without interaction. A common
      principle for no interaction is Loewe Additivity which is based on the assumption
      that no compound interacts with itself and that two doses from different
      compounds having the same effect are equivalent. It then should not matter
      whether a component is replaced by the other or vice versa. We call this
      assumption the Loewe Additivity Consistency Condition (LACC). We derive explicit
      and implicit null reference models from the Loewe Additivity principle that are
      equivalent when the LACC holds. Of these two formulations, the implicit
      formulation is the known General Isobole Equation (Loewe, 1928), whereas the
      explicit one is the novel contribution. The LACC is violated in a significant
      number of cases. In this scenario the models make different predictions. We
      analyze two data sets of drug screening that are non-interactive (Cokol et al.,
      2011; Yadav et al., 2015) and show that the LACC is mostly violated and Loewe
      Additivity not defined. Further, we compare the measurements of the non
      interactive cases of both data sets to the theoretical null reference models in
      terms of bias and mean squared error. We demonstrate that the explicit
      formulation of the null reference model leads to smaller mean squared errors than
      the implicit one and is much faster to compute.

PMID- 29467648
TI  - Dissecting Endoplasmic Reticulum Unfolded Protein Response (UPRER) in Managing
      Clandestine Modus Operandi of Alzheimer's Disease.
AB  - Alzheimer's disease (AD), a neurodegenerative disorder, is most common cause of
      dementia witnessed among aged people. The pathophysiology of AD develops as a
      consequence of neurofibrillary tangle formation which consists of
      hyperphosphorylated microtubule associated tau protein and senile plaques of
      amyloid-beta (Abeta) peptide in specific brain regions that result in synaptic
      loss and neuronal death. The feeble buffering capacity of endoplasmic reticulum
      (ER) proteostasis in AD is evident through alteration in unfolded protein
      response (UPR), where UPR markers express invariably in AD patient's brain
      samples. Aging weakens UPRER causing neuropathology and memory loss in AD. This
      review highlights molecular signatures of UPRER and its key molecular alliance
      that are affected in aging leading to the development of intriguing
      neuropathologies in AD. We present a summary of recent studies reporting usage of
      small molecules as inhibitors or activators of UPRER sensors/effectors in AD that
      showcase avenues for therapeutic interventions.

PMID- 29467651
TI  - Functional G-Protein-Coupled Receptor (GPCR) Synthesis: The Pharmacological
      Analysis of Human Histamine H1 Receptor (HRH1) Synthesized by a Wheat Germ Cell
      Free Protein Synthesis System Combined with Asolectin Glycerosomes.
AB  - G-protein-coupled receptors (GPCRs) are membrane proteins distributed on the cell
      surface, and they may be potential drug targets. However, synthesizing GPCRs in
      vitro can be challenging. Recently, some cell-free protein synthesis systems have
      been shown to produce a large amount of membrane protein combined with chemical
      chaperones that include liposomes and glycerol. Liposomes containing high
      concentrations of glycerol are known as glycerosomes, which are used in new drug
      delivery systems. Glycerosomes have greater morphological stability than
      liposomes. Proteoglycerosomes are defined as glycerosomes that contain membrane
      proteins. Human histamine H1 receptor (HRH1) is one of the most studied GPCRs. In
      this study, we synthesized wild-type HRH1 (WT-HRH1) proteoglycerosomes and D107A
      HRH1, (in which Asp107 was replaced by Ala) in a wheat germ cell-free protein
      synthesis system combined with asolectin glycerosomes. The mutant HRH1 has been
      reported to have low affinity for the H1 antagonist. In this study, the amount of
      synthesized WT-HRH1 in one synthesis reaction was 434 +/- 66.6 MUg (7.75 +/- 1.19
      * 103pmol). The specific binding of [3H]pyrilamine to the WT-HRH1
      proteoglycerosomes became saturated as the concentration of the radioligand
      increased. The dissociation constant (Kd) and maximum density (Bmax) of the
      synthesized WT-HRH1 were 9.76 +/- 1.25 nM and 21.4 +/- 0.936 pmol/mg protein,
      respectively. However, specific binding to D107A-HRH1 was reduced compared with
      WT-HRH1 and the binding did not become saturated. The findings of this study
      highlight that HRH1 synthesized using a wheat germ cell-free protein synthesis
      system combined with glycerosomes has the ability to bind to H1 antagonists.

PMID- 29467652
TI  - Quantitative Ethnobotany of Medicinal Plants Used by Indigenous Communities in
      the Bandarban District of Bangladesh.
AB  - This study documents information on significant ethnomedicinal plants, which was
      collected from the traditional healers of three indigenous communities of
      Bangladesh. The documented data were quantitatively analyzed for the first time
      in this area. The information was obtained through open-ended, semi-structured
      questionnaires. The benefits, importance and coverage of ethnomedicine were
      expressed through several quantitative indices including Informant Consensus
      Factor (ICF), Use Value (UV), Frequency of Citation (FC), Relative Frequency of
      Citation (RFC) and Relative Importance Index (RI). The agreement of homogeneity
      between the present and previous studies and among the indigenous communities was
      evaluated using the Jaccard Index (JI). A total of 159 ethnomedicinal plant
      species, which were distributed in 132 genera under 62 families, were documented
      from 174 informants. Of these, 128 plants were native and 31 were exotic. Of a
      majority of documented species, herbs and leaves were the most utilized plant
      parts for the preparation of ethnomedicines (45.28%) whereas pastes (63.03%) were
      the most popular formulations. Among the documented species, the dominant
      families were the Asteraceae (14 species) and the Lamiaceae (12 species). The
      highest ICF value was 0.77 for digestive system disorders. Based on UVs, the five
      most commonly used ethnomedicinal plant species in the study area were Duabanga
      grandiflora (0.43), Zingiber officinale (0.41), Congea tomentosa (0.40),
      Matricaria chamomilla (0.33) and Engelhardtia spicata (0.28). The highest RFC was
      recorded for Rauvolfia serpentina (0.25). The highest RI value was calculated for
      both Scoparia dulcis and Leucas aspera (0.83). Importantly, 16 species were
      reported with new therapeutic uses and to our knowledge, 7 species described
      herein have never been ethnobotanically and pharmacologically studied, viz:
      Agastache urticifolia, Asarum cordifolium, C. tomentosa, E. spicata, Hypserpa
      nitida, Merremia vitifolia and Smilax odoratissima. The present study showed that
      traditional treatment using medicinal plants is still widespread in the study
      area. Documentation of new ethnomedicinal species with their therapeutic uses
      shall promote further phytochemical and pharmacological investigations and
      possibly, lead to the development of new drugs.

PMID- 29467653
TI  - The Antioxidant Activity of Pistachios Reduces Cardiac Tissue Injury of Acute
      Ischemia/Reperfusion (I/R) in Diabetic Streptozotocin (STZ)-Induced
      Hyperglycaemic Rats.
AB  - Diabetes mellitus is an important risk factor for the development of heart
      pathology. Myocardial infarction is the cause of death occurring after prolonged
      ischemia of the coronary arteries. Restoration of blood flow is the first
      intervention against heart attack, although the process of restoring blood flow
      to the ischemic myocardium could cause additional injury. This phenomenon, termed
      myocardial ischemia-reperfusion (MI-R) injury, is characterized by the formation
      of oxygen radicals. Pistachios have significant glucose- and insulin-lowering
      effects and can improve the inflammatory contest by downregulating both the
      expression and the circulating levels of several metabolic risk markers. The
      monocyte/macrophage cell line J774 was used to assess the extent of protection by
      natural raw (NP) and roasted salted (RP) pistachios against lipopolysaccharide
      (LPS)-induced inflammation. Moreover, antioxidant activity of NP and RP was
      assessed in an in vivo model of paw edema in rats induced by carrageenan (CAR)
      injection in the paw. This study evaluates the antioxidant properties of
      pistachios on the inflammatory process associated with myocardial
      ischemia/reperfusion injury (I/R) in diabetic rats. Rats were pre-treated with
      either NP or RP pistachios (30 mg/kg) 18 h prior to the experimental procedure.
      Results: Here, we demonstrated that treatment with NP reduced myocardial tissue
      injury, neutrophil infiltration, adhesion molecules (ICAM-1, P-selectin)
      expression, proinflammatory cytokines (TNF-alpha, IL-1beta) production,
      nitrotyrosine and PAR formation, NF-kappaB expression and apoptosis (Bax, Bcl-2)
      activation. This data clearly showes modulation of the inflammatory process,
      associated with MI-R injury, following administration of pistachios.

PMID- 29467655
TI  - Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory
      Therapy: How Human Genetics Can Help to This Issue. A Narrative Review.
AB  - Atherosclerosis is a multifactorial disease triggered and sustained by different
      risk factors such as dyslipidemia, arterial hypertension, diabetes mellitus,
      smoke, etc. Since a couple of decades, a pivotal role for inflammation in its
      pathogenesis has been recognized and proved at molecular levels, and already
      described in many animal models. Despite all this knowledge, due to the
      complexity of the specific inflammatory process subtending atherosclerosis and to
      the fact that inflammation is also a protective response against microorganisms,
      no anti-inflammatory therapy has been rendered available in the therapeutic
      armamentarium against atherosclerosis and vascular events till 2017 when
      canakinumab in the first ad-hoc randomized clinical trial (RCT) proved for the
      first time that targeting specifically inflammation lowers cardiovascular (CV)
      events. From the genetic side, in the 90's and early 2000, several genetic
      markers in inflammatory pathway have been explored searching for an association
      with athero-thrombosis which gave seldom consistent results. Then, in the genomic
      era, plenty of genetic markers covering most of the genome have been analyzed at
      once without a priori information. The results coming from genome wide
      association studies (GWAS) have pinpointed some loci closed to inflammatory
      molecules consistently associated with atherosclerosis and CV consequences
      revamping the strict link between inflammation and atherosclerosis and suggesting
      some tailored target therapy. Whole-exome and whole-genome sequencing will come
      soon showing new and old loci associated with atherosclerosis suggesting new
      molecular targets or underlying which inflammatory pathway could be most
      attractive to target for blocking atherosclerosis even in its early stages.

PMID- 29467656
TI  - Sublingual Administration of Sildenafil Oro-dispersible Film: New Profiles of
      Drug Tolerability and Pharmacokinetics for PDE5 Inhibitors.
AB  - Objective: Type 5 phosphodiesterase inhibitors (PDE5i) are efficient drugs used
      for treatment of erectile dysfunction (ED); however, a large discontinuation rate
      due to major side effects is reported. The aim of this study was to evaluate the
      possible improvement of sildenafil (Sild) pharmacokinetics associated to the
      sublingual administration of the new available oro-dispersible film (ODF),
      compared to both the oro-dispersible tablet (ODT) and the film-coated tablet
      (FCT) as original per os formulation. Methods:In vitro disaggregation test,
      dissolution test, and permeation test in specific devices to estimate the trans
      mucosal absorption. In vivo analysis of serum Sild levels, by high performance
      liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), was performed in 20
      patients with psychogenic ED receiving alternatively per os FCT or sublingual ODT
      or ODF, at an equal dosage (50 mg). Pharmacokinetic parameters of Sild and
      adverse drug reactions experienced after the dosing of each formulation were
      compared. Results:In vitro, ODF showed the highest time to disaggregation and an
      increased rate of permeation compared to both ODT and FCT (P = 0.017 and P =
      0.008, respectively). In vivo, compared to both FCT and ODT, ODF showed a faster
      increase of serum Sild levels (serum levels at 15 min from dosing, respectively:
      2.24 +/- 1.4 ng/ml FCT, 0.5 +/- 0.3 ng/ml ODT, and 13.5 +/- 9.1 ng/ml ODF; P <
      0.01 and P < 0.05 vs. ODF) together with a higher drug bioavailability within 60
      min from dosing (relative AUC60min vs. FCT, respectively: 100.0 +/- 44.9% FCT,
      183.8 +/- 75.4% ODT, and 304.2 +/- 156.0% ODF). A trend toward lower peak serum
      levels was observed for ODF. Finally, ODF showed a lower prevalence of headache
      compared to FCT (1 vs. 35%; P < 0.05) and improved pattern of flushing and nasal
      congestion. Conclusion: Sublingual Sild ODF improves the drug tolerability
      through a likely modified pharmacokinetic, suggesting a possible implication also
      in the clinical efficacy profile. Sublingual administration of oro-dispersible
      formulations may represent a strategy to ameliorate the adherence to therapy with
      PDE5i, particularly in patients discouraged by side effects.

PMID- 29467657
TI  - Effects of Sodium and Amino Acid Substrate Availability upon the Expression and
      Stability of the SNAT2 (SLC38A2) Amino Acid Transporter.
AB  - The SNAT2 (SLC38A2) System A amino acid transporter mediates Na+-coupled cellular
      uptake of small neutral alpha-amino acids (AAs) and is extensively regulated in
      response to humoral and nutritional cues. Understanding the basis of such
      regulation is important given that AA uptake via SNAT2 has been linked to
      activation of mTORC1; a major controller of many important cellular processes
      including, for example, mRNA translation, lipid synthesis, and autophagy and
      whose dysregulation has been implicated in the development of cancer and
      conditions such as obesity and type 2 diabetes. Extracellular AA withdrawal
      induces an adaptive upregulation of SNAT2 gene transcription and SNAT2 protein
      stability but, as yet, the sensing mechanism(s) that initiate this response
      remain poorly understood although interactions between SNAT2 and its substrates
      may play a vital role. Herein, we have explored how changes in substrate (AA and
      Na+) availability impact upon the adaptive regulation of SNAT2 in HeLa cells. We
      show that while AA deprivation induces SNAT2 gene expression, this induction was
      not apparent if extracellular Na+ was removed during the AA withdrawal period.
      Furthermore, we show that the increase in SNAT2 protein stability associated with
      AA withdrawal is selectively repressed by provision of SNAT2 AA substrates (N
      methylaminoisobutyric acid and glutamine), but not non-substrates. This
      stabilization and substrate-induced repression were critically dependent upon the
      cytoplasmic N-terminal tail of SNAT2 (containing lysyl residues which are
      putative targets of the ubiquitin-proteasome system), because "grafting" this
      tail onto SNAT5, a related SLC38 family member that does not exhibit adaptive
      regulation, confers substrate-induced changes in stability of the SNAT2-5
      chimeric transporter. In contrast, expression of SNAT2 in which the N-terminal
      lysyl residues were mutated to alanine rendered the transporter stable and
      insensitive to substrate-induced changes in protein stability. Intriguingly,
      SNAT2 protein stability was dramatically reduced in the absence of extracellular
      Na+ irrespective of whether substrate AAs were present or absent. Our findings
      indicate that the presence of extracellular Na+ (and potentially its binding to
      SNAT2) may be crucial for not only sensing SNAT2 AA occupancy and consequently
      for initiating the adaptive response under AA insufficient conditions, but for
      enabling substrate-induced changes in SNAT2 protein stability.

PMID- 29467658
TI  - How Do Structurally Distinct Compounds Exert Functionally Identical Effects in
      Combating Obesity?
AB  - Although the concept of inflammatory obesity remains to be widely accepted, a
      plethora of antibiotics, anti-inflammatory agents, mitochondrial uncouplers, and
      other structurally distinct compounds with unknown mechanisms have been
      demonstrated to exert functionally identical effects on weight reduction. Here we
      summarize a universal mechanism in which weight loss is modulated by
      mitochondrial biogenesis, which is correlated with conversion from the
      mitochondria-insufficient white adipose tissue to the mitochondria-abundant brown
      adipose tissue. This mechanistic description of inflammatory obesity may prove
      useful in the future for guiding pathology-based drug discovery for weight
      reduction.

PMID- 29467659
TI  - Transfer and Multi-task Learning in QSAR Modeling: Advances and Challenges.
AB  - Medicinal chemistry projects involve some steps aiming to develop a new drug,
      such as the analysis of biological targets related to a given disease, the
      discovery and the development of drug candidates for these targets, performing
      parallel biological tests to validate the drug effectiveness and side effects.
      Approaches as quantitative study of activity-structure relationships (QSAR)
      involve the construction of predictive models that relate a set of descriptors of
      a chemical compound series and its biological activities with respect to one or
      more targets in the human body. Datasets used to perform QSAR analyses are
      generally characterized by a small number of samples and this makes them more
      complex to build accurate predictive models. In this context, transfer and multi
      task learning techniques are very suitable since they take information from other
      QSAR models to the same biological target, reducing efforts and costs for
      generating new chemical compounds. Therefore, this review will present the main
      features of transfer and multi-task learning studies, as well as some
      applications and its potentiality in drug design projects.

PMID- 29467654
TI  - The P2X7 Receptor in Inflammatory Diseases: Angel or Demon?
AB  - Under physiological conditions, adenosine triphosphate (ATP) is present at low
      levels in the extracellular milieu, being massively released by stressed or dying
      cells. Once outside the cells, ATP and related nucleotides/nucleoside generated
      by ectonucleotidases mediate a high evolutionary conserved signaling system: the
      purinergic signaling, which is involved in a variety of pathological conditions,
      including inflammatory diseases. Extracellular ATP has been considered an
      endogenous adjuvant that can initiate inflammation by acting as a danger signal
      through the activation of purinergic type 2 receptors-P2 receptors (P2Y G-protein
      coupled receptors and P2X ligand-gated ion channels). Among the P2 receptors, the
      P2X7 receptor is the most extensively studied from an immunological perspective,
      being involved in both innate and adaptive immune responses. P2X7 receptor
      activation induces large-scale ATP release via its intrinsic ability to form a
      membrane pore or in association with pannexin hemichannels, boosting purinergic
      signaling. ATP acting via P2X7 receptor is the second signal to the inflammasome
      activation, inducing both maturation and release of pro-inflammatory cytokines,
      such as IL-1beta and IL-18, and the production of reactive nitrogen and oxygen
      species. Furthermore, the P2X7 receptor is involved in caspases activation, as
      well as in apoptosis induction. During adaptive immune response, P2X7 receptor
      modulates the balance between the generation of T helper type 17 (Th17) and T
      regulatory (Treg) lymphocytes. Therefore, this receptor is involved in several
      inflammatory pathological conditions. In infectious diseases and cancer, P2X7
      receptor can have different and contrasting effects, being an angel or a demon
      depending on its level of activation, cell studied, type of pathogen, and
      severity of infection. In neuroinflammatory and neurodegenerative diseases, P2X7
      upregulation and function appears to contribute to disease progression. In this
      review, we deeply discuss P2X7 receptor dual function and its pharmacological
      modulation in the context of different pathologies, and we also highlight the
      P2X7 receptor as a potential target to treat inflammatory related diseases.

PMID- 29467660
TI  - Advantages and Limitations of Current Imaging Techniques for Characterizing
      Liposome Morphology.
AB  - There are currently a number of imaging techniques available for evaluating the
      morphology of liposomes and other nanoparticles, with each having its own
      advantages and disadvantages that should be considered when interpreting data.
      Controlling and validating the morphology of nanoparticles is of key importance
      for the effective clinical translation of liposomal formulations. There are a
      number of physical characteristics of liposomes that determine their in vivo
      behavior, including size, surface characteristics, lamellarity, and homogeneity.
      Despite the great importance of the morphology of nanoparticles, it is generally
      not well-characterized and is difficult to control. Appropriate imaging
      techniques provide important details regarding the morphological characteristics
      of nanoparticles, and should be used in conjunction with other methods to assess
      physicochemical parameters. In this review, we will discuss the advantages and
      limitations of available imaging techniques used to evaluate liposomal
      formulations.

PMID- 29467661
TI  - Functionalized Surface Geometries Induce: "Bone: Formation by Autoinduction".
AB  - The induction of tissue formation, and the allied disciplines of tissue
      engineering and regenerative medicine, have flooded the twenty-first century
      tissue biology scenario and morphed into high expectations of a fulfilling
      regenerative dream of molecularly generated tissues and organs in assembling
      human tissue factories. The grand conceptualization of deploying soluble
      molecular signals, first defined by Turing as forms generating substances, or
      morphogens, stemmed from classic last century studies that hypothesized the
      presence of morphogens in several mineralized and non-mineralized mammalian
      matrices. The realization of morphogens within mammalian matrices devised
      dissociative extractions and chromatographic procedures to isolate, purify, and
      finally reconstitute the cloned morphogens, found to be members of the
      transforming growth factor-beta (TGF-beta) supergene family, with insoluble
      signals or substrata to induce de novo tissue induction and morphogenesis. Can we
      however construct macroporous bioreactors per se capable of inducing bone
      formation even without the exogenous applications of the osteogenic soluble
      molecular signals of the TGF-beta supergene family? This review describes
      original research on coral-derived calcium phosphate-based macroporous constructs
      showing that the formation of bone is independent of the exogenous application of
      the osteogenic soluble signals of the TGF-beta supergene family. Such signals are
      the molecular bases of the induction of bone formation. The aim of this review is
      to primarily describe today's hottest topic of biomaterials' science, i.e., to
      construct and define osteogenetic biomaterials' surfaces that per se, in its own
      right, do initiate the induction of bone formation. Biomaterials are often used
      to reconstruct osseous defects particularly in the craniofacial skeleton.
      Edentulism did spring titanium implants as tooth replacement strategies. No were
      else that titanium surfaces require functionalized geometric nanotopographic cues
      to set into motion osteogenesis independently of the exogenous application of the
      osteogenic soluble molecular signals. Inductive morphogenetic surfaces are the
      way ahead of biomaterials' science: the connubium of stem cells on primed
      functionalized surfaces precisely regulates gene expression and the induction of
      the osteogenic phenotype.

PMID- 29467663
TI  - Ranolazine Attenuates Trastuzumab-Induced Heart Dysfunction by Modulating ROS
      Production.
AB  - The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can
      cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to
      counter experimental HF, including doxorubicin cardiotoxicity (a condition
      characterized by derangements in redox balance), by lowering the levels of
      reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested
      whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox
      mediated mechanisms. Trastuzumab decreased fractional shortening and ejection
      fraction in mice, but ranolazine prevented heart dysfunction when co-administered
      with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in
      natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not
      elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage
      of caspase-3, indicating activation of the proapoptotic machinery. Again,
      ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular
      Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab,
      showed only a small increase in ROS compared to baseline conditions. We then
      stressed trastuzumab-treated cells with the beta-agonist isoproterenol to
      increase workload, and we observed a significant increase of probe fluorescence,
      compared with cells treated with isoproterenol alone, reflecting induction of
      oxidative stress. These effects were blunted by ranolazine, supporting a role for
      INa inhibition in the regulation of redox balance also in trastuzumab
      cardiotoxicity.

PMID- 29467662
TI  - Purinergic Signaling in Neuron-Astrocyte Interactions, Circadian Rhythms, and
      Alcohol Use Disorder.
AB  - Alcohol use disorder (AUD) is a debilitating condition marked by cyclic patterns
      of craving, use, and withdrawal. These pathological behaviors are mediated by
      multiple neurotransmitter systems utilizing glutamate, GABA, dopamine, ATP, and
      adenosine. In particular, purines such as ATP and adenosine have been
      demonstrated to alter the phase and function of the circadian clock and are
      reciprocally regulated by the clock itself. Importantly, chronic ethanol intake
      has been demonstrated to disrupt the molecular circadian clock and is associated
      with altered circadian patterns of activity and sleep. Moreover, ethanol has been
      demonstrated to disrupt purinergic signaling, while dysfunction of the purinergic
      system has been implicated in conditions of drug abuse such as AUD. In this
      review, we summarize our current knowledge regarding circadian disruption by
      ethanol, focusing on the reciprocal relationship that exists between oscillatory
      neurotransmission and the molecular circadian clock. In particular, we offer
      detailed explanations and hypotheses regarding the concerted regulation of
      purinergic signaling and circadian oscillations by neurons and astrocytes, and
      review the diverse mechanisms by which purinergic dysfuction may contribute to
      circadian disruption or alcohol abuse. Finally, we describe the mechanisms by
      which ethanol may disrupt or hijack endogenous circadian rhythms to induce the
      maladaptive behavioral patterns associated with AUD.

PMID- 29467664
TI  - Peak Velocity as an Alternative Method for Training Prescription in Mice.
AB  - Purpose: To compare the efficiency of an aerobic physical training program
      prescribed according to either velocity associated with maximum oxygen uptake
      (vVO2max) or peak running speed obtained during an incremental treadmill test
      (Vpeak_K) in mice. Methods: Twenty male Swiss mice, 60 days old, were randomly
      divided into two groups with 10 animals each: 1. group trained by vVO2max (GVO2),
      2. group trained by Vpeak_K (GVP). After the adaptation training period, an
      incremental test was performed at the beginning of each week to adjust training
      load and to determine the amount of VO2 and VCO2 fluxes consumed, energy
      expenditure (EE) and run distance during the incremental test. Mice were
      submitted to 4 weeks of aerobic exercise training of moderate intensity (velocity
      referring to 70% of vVO2max and Vpeak_K) in a programmable treadmill. The
      sessions lasted from 30 to 40 min in the first week, to reach 60 min in the
      fourth week, in order to provide the mice with a moderate intensity exercise,
      totaling 20 training sessions. Results: Mice demonstrated increases in VO2max
      (ml.kg-1.min-1) (GVO2 = 49.1% and GVP = 56.2%), Vpeak_K (cm.s-1) (GVO2 = 50.9%
      and GVP = 22.3%), EE (ml.kg-0,75.min-1) (GVO2 = 39.9% and GVP = 51.5%), and run
      distance (cm) (GVO2 = 43.5% and GVP = 33.4%), after 4 weeks of aerobic training
      (time effect, P < 0.05); there were no differences between the groups.
      Conclusions: Vpeak_K, as well as vVO2max, can be adopted as an alternative test
      to determine the performance and correct prescription of systemized aerobic
      protocol training to mice.

PMID- 29467665
TI  - Analysis of microRNA Expression Profiles Induced by Yiqifumai Injection in Rats
      with Chronic Heart Failure.
AB  - Background: Yiqifumai Injection (YQFM) is clinically used to treat various
      cardiovascular diseases including chronic heart failure (CHF). The efficacy of
      YQFM for treating heart failure has been suggested, but the mechanism of action
      for pharmacological effects of YQFM is unclear. Methods: Echocardiography
      detection, left ventricular intubation evaluation, histopathology and
      immunohistochemical examination were performed in CHF rats to evaluate the
      cardioprotective effect of YQFM. Rat miRNA microarray and bioinformatics analysis
      were employed to investigate the differentially expressed microRNAs. In vitro
      models of AngII-induced hypertrophy and t-BHP induced oxidative stress in H9c2
      myocardial cells were used to validate the anti-hypertrophy and anti-apoptosis
      effects of YQFM. Measurement of cell surface area, ATP content and cell
      viability, Real-time PCR and Western blot were performed. Results: YQFM
      significantly improved the cardiac function of CHF rats by increasing left
      ventricular ejection fraction and fractional shortening, decreasing left
      ventricular internal diameter and enhancing cardiac output. Seven microRNAs which
      have a reversible regulation by YQFM treatment were found. Among them, miR-21-3p
      and miR-542-3p are related to myocardial hypertrophy and cell proliferation,
      respectively and were further verified by RT-PCR. Target gene network was
      established and potential related signaling pathways were predicted. YQFM could
      significantly alleviate AngII induced hypertrophy in cellular model. It also
      significantly increased cell viabilities and ATP content in t-BHP induced
      apoptotic cell model. Western blot analysis showed that YQFM could increase the
      phosphorylation of Akt. Conclusion: Our findings provided scientific evidence to
      uncover the mechanism of action of YQFM on miRNAs regulation against CHF by miRNA
      expression profile technology. The results indicated that YQFM has a potential
      effect on alleviate cardiac hypertrophy and apoptosis in chronic heart failure.

PMID- 29467666
TI  - Time Course and Association of Functional and Biochemical Markers in Severe
      Semitendinosus Damage Following Intensive Eccentric Leg Curls: Differences
      between and within Subjects.
AB  - Purpose: To investigate the extent and evolution of hamstring muscle damage
      caused by an intensive bout of eccentric leg curls (ELCs) by (1) assessing the
      time course and association of different indirect markers of muscle damage such
      as changes in the force-generating capacity (FGC), functional magnetic resonance
      (fMRI), and serum muscle enzyme levels and (2) analyzing differences in the
      degree of hamstring muscle damage between and within subjects (limb-to-limb
      comparison). Methods: Thirteen male participants performed six sets of 10
      repetitions of an ELC with each leg. Before and at regular intervals over 7 days
      after the exercise, FGC was measured with maximal isometric voluntary contraction
      (MVC). Serum enzyme levels, fMRI transverse relaxation time (T2) and perceived
      muscle soreness were also assessed and compared against the FGC. Results: Two
      groups of subjects were identified according to the extent of hamstring muscle
      damage based on decreased FGC and increased serum enzyme levels: high responders
      (n = 10, severe muscle damage) and moderate responders (n = 3, moderate muscle
      damage). In the high responders, fMRI T2 analysis revealed that the
      semitendinosus (ST) muscle suffered severe damage in the three regions measured
      (proximal, middle, and distal). The biceps femoris short head (BFsh) muscle was
      also damaged and there were significant differences in the FGC within subjects in
      the high responders. Conclusion: FGC and serum enzyme levels measured in 10 of
      the subjects from the sample were consistent with severe muscle damage. However,
      the results showed a wide range of peak MVC reductions, reflecting different
      degrees of damage between subjects (high and moderate responders). fMRI analysis
      confirmed that the ST was the hamstring muscle most damaged by ELCs, with uniform
      T2 changes across all the measured sections of this muscle. During intensive
      ELCs, the ST muscle could suffer an anomalous recruitment pattern due to fatigue
      and damage, placing an excessive load on the BFsh and causing it to perform a
      synergistic compensation that leads to structural damage. Finally, T2 and MVC
      values did not correlate for the leg with the smaller FGC decrease in the
      hamstring muscles, suggesting that long-lasting increases in T2 signals after FGC
      markers have returned to baseline values might indicate an adaptive process
      rather than damage.

PMID- 29467667
TI  - Absence of Rapid Propagation through the Purkinje Network as a Potential Cause of
      Line Block in the Human Heart with Left Bundle Branch Block.
AB  - Background: Cardiac resynchronization therapy is an effective device therapy for
      heart failure patients with conduction block. However, a problem with this
      invasive technique is the nearly 30% of non-responders. A number of studies have
      reported a functional line of block of cardiac excitation propagation in
      responders. However, this can only be detected using non-contact endocardial
      mapping. Further, although the line of block is considered a sign of responders
      to therapy, the mechanism remains unclear. Methods: Herein, we created two
      patient-specific heart models with conduction block and simulated the propagation
      of excitation based on a cellmodel of electrophysiology. In one model with a
      relatively narrow QRS width (176 ms), we modeled the Purkinje network using a
      thin endocardial layer with rapid conduction. To reproduce a wider QRS complex
      (200 ms) in the second model, we eliminated the Purkinje network, and we
      simulated the endocardial mapping by solving the inverse problem according to the
      actual mapping system. Results: We successfully observed the line of block using
      non-contact mapping in the model without the rapid propagation of excitation
      through the Purkinje network, although the excitation in the wall propagated
      smoothly. This model of slow conduction also reproduced the characteristic
      properties of the line of block, including dense isochronal lines and
      fractionated local electrocardiograms. Further, simulation of ventricular pacing
      from the lateral wall shifted the location of the line of block. By contrast, in
      the model with the Purkinje network, propagation of excitation in the endocardial
      map faithfully followed the actual propagation in the wall, without showing the
      line of block. Finally, switching the mode of propagation between the two models
      completely reversed these findings. Conclusions: Our simulation data suggest that
      the absence of rapid propagation of excitation through the Purkinje network is
      the major cause of the functional line of block recorded by non-contact
      endocardial mapping. The line of block can be used to identify responders as
      these patients loose rapid propagation through the Purkinje network.

PMID- 29467668
TI  - Identification and Functional Analysis of the First Aquaporin from Striped Stem
      Borer, Chilo suppressalis.
AB  - Aquaporins are integral membrane proteins some of which form high capacity water
      selective channels, promoting water permeation across cell membranes. In this
      study, we isolated the aquaporin transcript (CsDrip1) of Chilo suppressalis, one
      of the important rice pests. CsDrip1 included two variants, CsDrip1_v1 and
      CsDrip1_v2. Although CsDrip1_v2 sequence (>409 bp) was longer than CsDrip1_v1,
      they possessed the same open reading frame (ORF). Protein structure and topology
      of CsDrip1 was analyzed using a predicted model, and the results demonstrated the
      conserved properties of insect water-specific aquaporins, including 6
      transmembrane domains, 2 NPA motifs, ar/R constriction region (Phe69, His194,
      Ser203, and Arg209) and the C-terminal peptide sequence ending in "SYDF." Our
      data revealed that the Xenopus oocytes expressing CsDrip1 indicated CsDrip1 could
      transport water instead of glycerol, trehalose and urea. Further, the transcript
      of CsDrip1 expressed ubiquitously but differentially in different tissues or
      organs and developmental stages of C. suppressalis. CsDrip1 mRNA exhibited the
      highest level of expression within hindgut and the third instar larvae.
      Regardless of pupae and adults, there were significantly different expression
      levels of CsDrip1 gene between male and female. Different from at low
      temperature, the transcript of CsDrip1 in larvae exposed to high temperature was
      increased significantly. Moreover, the mRNA levels of CsDrip1 in the third instar
      larvae, the fifth instar larvae, pupae (male and female), and adults (male and
      female) under different humidities were investigated. However, the mRNA levels of
      CsDrip1 of only female and male adults were changed remarkably. In conclusions,
      CsDrip1 plays important roles in maintaining water homeostasis in this important
      rice pest.

PMID- 29467669
TI  - Establishment and Evaluation of a Rat Model of Sidestream Cigarette Smoke-Induced
      Chronic Obstructive Pulmonary Disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a common cause of mortality
      worldwide. The current lack of an animal model that can be established within a
      certain time frame and imitate the unique features of the disease is a major
      limiting factor in its study. The present study established and evaluated an
      animal model of COPD that represents the early and advanced stage features using
      short-, middle-, and long-term sidestream cigarette smoke (CS) exposure. One
      hundred and nine Sprague-Dawley rats were randomly divided into 10 groups for
      different periods of sidestream CS exposure or no exposure (i.e., normal groups).
      The rats were exposed to CS from 3R4F cigarettes in an exposure chamber.
      Histological analysis was performed to determine pathological changes. We also
      conducted open-field tests, lung function evaluations, and cytokine analysis of
      the blood serum, bronchoalveolar lavage fluid, and lung tissue. The lung tissue
      protein levels, blood gases, and were also analyzed. As the CS exposure time
      increased, the indicators associated with oxidative stress, inflammatory
      responses, and airway remodeling were greater in the CS exposure groups than in
      the normal group. At 24 and 36 weeks, the COPD model rats displayed the middle-
      and advanced-stage features of COPD, respectively. In the 8-week CS exposure
      group, after the CS exposure was stopped for 4 weeks, inflammatory responses and
      oxidative responses were ameliorated and lung function exacerbation was reduced
      compared with the 12-week CS exposure group. Therefore, we established a more
      adequate rat model of sidestream CS induced COPD, which will have great
      significance for a better understanding of the pathogenesis of COPD and drug
      effectiveness evaluation.

PMID- 29467670
TI  - Zinc-alpha2-Glycoprotein Is Associated with Obesity in Chinese People and HFD
      Induced Obese Mice.
AB  - Zinc-alpha2-glycoprotein (ZAG) plays an important role in the regulation of body
      weight, body fat, and glucose metabolism. In this study, we first measured ZAG
      levels in serum and ZAG mRNA levels in subcutaneous white adipose tissue (sWAT)
      among overweight/obese patients and lean control subjects. Second, we
      investigated the effects of ZAG administration on the body weight, body fat and
      glucose metabolism of high-fat diet (HFD)-induced obese ICR mice and the possible
      mechanisms involved. The results showed that serum ZAG and mRNA levels in sWAT
      were significantly decreased in overweight/obese patients and that both showed a
      negative association with body mass index (BMI) and body weight after adjustment
      for age and sex. Further partial correlation analysis found that ZAG mRNA
      expression was positively related with several WAT browning-related genes,
      including uncoupling protein 1 (UCP1) (r = 0.67) and peroxisome proliferator
      activated receptor gamma coactivator 1 alpha (PGC1a) (r = 0.60), in the sWAT of
      all subjects. Additionally, intraperitoneal injection of a ZAG expression plasmid
      (5 MUg/injection, four times a week) in HFD-induced obese mice for 8 weeks
      demonstrated that ZAG overexpression significantly decreased body weight and WAT
      mass, and greatly increased the glucose tolerance of obese mice, as shown by the
      intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin
      tolerance test (IPITT). The staining of UCP1-positive adipocytes was
      significantly stronger in the sWAT of ZAG-treated obese mice than in that of
      obese control mice. The mRNA and protein levels of PGC1alpha in sWAT were
      significantly increased to 2.2- and 5.3-fold, respectively, compared with HFD
      obese mice, and there was a strong positive correlation between the expression
      levels of Zag and Pgc1alpha in mouse sWAT (r = 0.74). A similar phenomenon was
      also observed in visceral white adipose tissue (vWAT): the mRNA and protein
      levels of PGC1alpha were increased to 1.9- and 3.6-fold, respectively, when obese
      mice were treated with ZAG. In conclusion, ZAG levels in both sWAT and serum are
      inversely related with BMI and body weight in Chinese subjects. The action of ZAG
      on body weight, fat mass and glucose metabolism may be realized through
      activating PGC1alpha expression in sWAT and vWAT, then promoting WAT browning in
      obese mice.

PMID- 29467671
TI  - TNF-alpha Increases Production of Reactive Oxygen Species through Cdk5 Activation
      in Nociceptive Neurons.
AB  - The participation of reactive oxygen species (ROS) generated by NOX1 and
      NOX2/NADPH oxidase has been documented during inflammatory pain. However, the
      molecular mechanism involved in their activation is not fully understood. We
      reported earlier a key role of Cyclin-dependent kinase 5 (Cdk5) during
      inflammatory pain. In particular, we demonstrated that TNF-alpha increased p35
      expression, a Cdk5 activator, causing Cdk5-mediated TRPV1 phosphorylation
      followed by an increment in Ca2+ influx in nociceptive neurons and increased pain
      sensation. Here we evaluated if Cdk5 activation mediated by p35 transfection in
      HEK293 cells or by TNF-alpha treatment in primary culture of nociceptive neurons
      could increase ROS production. By immunofluorescence we detected the expression
      of catalytic subunit (Nox1 and Nox2) and their cytosolic regulators (NOXO1 and
      p47phox) of NOX1 and NOX2/NADPH oxidase complexes, and their co-localization with
      Cdk5/p35 in HEK293 cells and in nociceptive neurons. By using a hydrogen peroxide
      sensor, we detected a significant increase of ROS production in p35 transfected
      HEK293 cells as compared with control cells. This effect was significantly
      blocked by VAS2870 (NADPH oxidase inhibitor) or by roscovitine (Cdk5 activity
      inhibitor). Also by using another ROS probe named DCFH-DA, we found a significant
      increase of ROS production in nociceptive neurons treated with TNF-alpha and this
      effect was also blocked by VAS2870 or by roscovitine treatment. Interestingly,
      TNF-alpha increased immunodetection of p35 protein and NOX1 and NOX2/NADPH
      oxidase complexes in primary culture of trigeminal ganglia neurons. Finally, the
      cytosolic regulator NOXO1 was significantly translocated to plasma membrane after
      TNF-alpha treatment and roscovitine blocked this effect. Altogether these results
      suggest that Cdk5 activation is implicated in the ROS production by NOX1 and
      NOX2/NADPH oxidase complexes during inflammatory pain.

PMID- 29467672
TI  - Serum Iron Levels Decreased in Patients with HBV-Related Hepatocellular
      Carcinoma, as a Risk Factor for the Prognosis of HBV-Related HCC.
AB  - Background: Hepatocellular carcinoma (HCC) is common and the second leading
      causes of cancer-related deaths. HCC usually occurs on the basis of chronic liver
      diseases. At present, the study of iron metabolism in chronic liver diseases was
      limited to chronic HCV infection, nonalcoholic fatty liver disease, and alcoholic
      liver disease. This study aimed to investigate the effect of serum iron levels on
      the progression of chronic HBV infection and the relationship with the prognosis
      of HBV-related HCC. Methods: A respective study involving 277 healthy individuals
      as controls (HC), 295 patients with chronic hepatitis B (CHB), 224 patients with
      HBV-related liver cirrhosis (HBV-related LC), and 586 patients with HBV- related
      HCC were enrolled in this study. Hematological parameters, HBVDNA and liver
      biochemistry were analyzed. Child-Pugh grade and BCLC stage of the HBV-related
      HCC patients were calculated. Results: The serum iron levels were lowest in the
      HBV- related HCC group as compared with HC, CHB, and HBV-related LC groups (35.07
      +/- 6.97, 27.37 +/- 10.26, 24.53 +/- 10.36 vs. 17.90 +/- 0.14, P < 0.001).
      Strikingly, serum iron levels were lowest in HBV- related HCC patients with tumor
      size more than 10 cm as compared with HBV- related HCC patients with tumor size
      smaller than 3, 3-5, and 5-10 cm by subgroup analysis (22.12 +/- 0.94, 21.44 +/-
      1.41, 15.65 +/- 0.98 vs. 13.36 +/- 1.15, P < 0.001). Serum iron levels
      significantly decreased with worsening Child-Pugh grades and BCLC stages in HBV
      related HCC group. In addition, serum iron levels was positively correlated with
      Retinol-Binding Protein, total bile acid, hemoglobin, and lymphocyte and
      negatively correlated with white blood cell (WBC) and platelet in HBV- related
      HCC group. ROC curve analysis showed serum iron levels at 15.1 MUmol/L as the
      optimal cut-off point for determining the survival of HBV-related HCC. By the Cox
      regression model analysis, serum iron levels <15.1 MUmol/l together with higher
      AFP levels, worse BCLC stages, and larger tumor size showed higher mortality of
      HBV-related HCC patients (hazard ratio = 2.280, 95% confidence interval, 1.815
      2.865; P < 0.001). Conclusions: Serum iron levels affected the progression of
      chronic HBV infection. The prognosis of HBV- related HCC patients with serum iron
      levels <15.1 MUmol/l together with higher AFP levels, worse BCLC stages, and
      larger tumor lesion were poor.

PMID- 29467673
TI  - Gait Complexity and Regularity Are Differently Modulated by Treadmill Walking in
      Parkinson's Disease and Healthy Population.
AB  - Variability raises considerable interest as a promising and sensitive marker of
      dysfunction in physiology, in particular in neurosciences. Both internally (e.g.,
      pathology) and/or externally (e.g., environment) generated perturbations and the
      neuro-mechanical responses to them contribute to the fluctuating dynamics of
      locomotion. Defective internal gait control in Parkinson's disease (PD),
      resulting in typical timing gait disorders, is characterized by the breakdown of
      the temporal organization of stride duration variability. Influence of external
      cue on gait pattern could be detrimental or advantageous depending on situations
      (healthy or pathological gait pattern, respectively). As well as being an
      interesting rehabilitative approach in PD, treadmills are usually implemented in
      laboratory settings to perform instrumented gait analysis including gait
      variability assessment. However, possibly acting as an external pacemaker,
      treadmill could modulate the temporal organization of gait variability of PD
      patients which could invalidate any gait variability assessment. This study aimed
      to investigate the immediate influence of treadmill walking (TW) on the temporal
      organization of stride duration variability in PD and healthy population. Here,
      we analyzed the gait pattern of 20 PD patients and 15 healthy age-matched
      subjects walking on overground and on a motorized-treadmill (randomized order) at
      a self-selected speed. The temporal organization and regularity of time series of
      walking were assessed on 512 consecutive strides and assessed by the application
      of non-linear mathematical methods (i.e., the detrended fluctuation analysis and
      power spectral density; and sample entropy, for the temporal organization and
      regularity of gait variability, respectively). A more temporally organized and
      regular gait pattern seems to emerge from TW in PD while no influence was
      observed on healthy gait pattern. Treadmill could afford the necessary framework
      to regulate gait rhythmicity in PD. Overall, the results support the hypothesis
      of a greater dependence to regulatory inputs as an explanatory factor of
      treadmill influence observed in PD. Also, since treadmill misrepresents the gait
      as more healthy than it is, the present findings underline that gait analysis
      using treadmill devices should be cautiously considered in PD and especially for
      gait variability assessment in gait lab.

PMID- 29467674
TI  - An Improved Dynamic Model for the Respiratory Response to Exercise.
AB  - Respiratory system modeling has been extensively studied in steady-state
      conditions to simulate sleep disorders, to predict its behavior under ventilatory
      diseases or stimuli and to simulate its interaction with mechanical ventilation.
      Nevertheless, the studies focused on the instantaneous response are limited,
      which restricts its application in clinical practice. The aim of this study is
      double: firstly, to analyze both dynamic and static responses of two known
      respiratory models under exercise stimuli by using an incremental exercise
      stimulus sequence (to analyze the model responses when step inputs are applied)
      and experimental data (to assess prediction capability of each model). Secondly,
      to propose changes in the models' structures to improve their transient and
      stationary responses. The versatility of the resulting model vs. the other two is
      shown according to the ability to simulate ventilatory stimuli, like exercise,
      with a proper regulation of the arterial blood gases, suitable constant times and
      a better adjustment to experimental data. The proposed model adjusts the
      breathing pattern every respiratory cycle using an optimization criterion based
      on minimization of work of breathing through regulation of respiratory frequency.

PMID- 29467676
TI  - Effect of Heart rate on Basketball Three-Point Shot Accuracy.
AB  - The three-point shot (3S) is a fundamental basketball skill used frequently
      during a game, and is often a main determinant of the final result. The aim of
      the study was to investigate the effect of different metabolic conditions, in
      terms of heart rates, on 3S accuracy (3S%) in 24 male (Under 17) basketball
      players (age 16.3 +/- 0.6 yrs). 3S performance was specifically investigated at
      different heart rates. All sessions consisted of 10 consecutive 3Ss from five
      different significant field spots just beyond the FIBA three-point line, i.e.,
      about 7 m from the basket (two counter-clockwise "laps") at different heart
      rates: rest (0HR), after warm-up (50%HRMAX [50HR]), and heart rate corresponding
      to 80% of its maximum value (80%HRMAX [80HR]). We found that 50HR does not
      significantly decrease 3S% (-15%, P = 0.255), while 80HR significantly does when
      compared to 0HR (-28%, P = 0.007). Given that 50HR does not decrease 3S% compared
      to 0HR, we believe that no preliminary warm-up is needed before entering a game
      in order to specifically achieve a high 3S%. Furthermore, 3S training should be
      performed in conditions of moderate-to-high fatigued state so that a high 3S% can
      be maintained during game-play.

PMID- 29467675
TI  - PVAT and Its Relation to Brown, Beige, and White Adipose Tissue in Development
      and Function.
AB  - Adipose tissue is commonly categorized into three types with distinct functions,
      phenotypes, and anatomical localizations. White adipose tissue (WAT) is the major
      energy store; the largest depots of WAT are found in subcutaneous or
      intravisceral sites. Brown adipose tissue (BAT) is responsible for energy
      dissipation during cold-exposure (i.e., non-shivering thermogenesis) and is
      primarily located in the interscapular region. Beige or brite (brown-in-white)
      adipose tissue can be found interspersed in WAT and can attain a brown-like
      phenotype. These three types of tissues also have endocrine functions and play
      major roles in whole body metabolism especially in obesity and its co
      morbidities, such as cardiovascular disease. Over the last years, perivascular
      adipose tissue (PVAT) has emerged as an adipose organ with endocrine and
      paracrine functions. Pro and anti-inflammatory agents released by PVAT affect
      vascular health, and are implicated in the inflammatory aspects of
      atherosclerosis. PVAT shares several of the defining characteristics of brown
      adipose tissue, including its cellular morphology and expression of thermogenic
      genes characteristic for brown adipocytes. However, PVATs from different vessels
      are phenotypically different, and significant developmental differences exist
      between PVAT and other adipose tissues. Whether PVAT represents classical BAT,
      beige adipose tissue, or WAT with changing characteristics, is unclear. In this
      review, we summarize the current knowledge on how PVAT relates to other types of
      adipose tissue, both in terms of functionality, developmental origins, and its
      role in obesity-related cardiovascular disease and inflammation.

PMID- 29467677
TI  - Ginsenoside Rg1 Ameliorates Rat Myocardial Ischemia-Reperfusion Injury by
      Modulating Energy Metabolism Pathways.
AB  - As a major ingredient of Radix ginseng, ginsenoside Rg1 (Rg1) has been
      increasingly recognized to benefit the heart condition, however, the rationale
      behind the role is not fully understood. In vitro study in H9c2 cardiomyocytes
      has shown the potential of Rg1 to increase ATP content in the cells. We thus
      speculated that the protective effect of Rg1 on heart ischemia and reperfusion
      (I/R) injury implicates energy metabolism regulation. The present study was
      designed to verify this speculation. Male Sprague-Dawley rats were subjected to
      30 min of occlusion of left coronary anterior descending artery followed by
      reperfusion for 90 min. Rg1 (5 mg/kg/h) was continuously administrated
      intravenously 30 min before occlusion until the end of reperfusion. Myocradial
      blood flow and heart function were monitored over the period of I/R. Myocardial
      infarct size, structure and apoptosis, energy metabolism, and change in RhoA
      signaling pathway were evaluated 90 min after reperfusion. Binding of Rg1 to RhoA
      was assessed using Surface Plasmon Resonance (SPR). Rg1 prevented I/R-elicited
      insults in myocardium, including myocardial infarction and apoptosis, decreased
      myocardial blood flow (MBF) and heart function, and alteration in myocardium
      structure. Rg1 restored the production of ATP in myocardium after I/R. Rg1 was
      able to bind to RhoA and down-regulate the activity of RhoA signaling pathway.
      These results indicated that Rg1 had protective potential against I/R-induced
      myocardial injury, which may be related to inhibiting myocardial apoptosis and
      modulating energy metabolism through binding to RhoA.

PMID- 29467678
TI  - Structural Immaturity of Human iPSC-Derived Cardiomyocytes: In Silico
      Investigation of Effects on Function and Disease Modeling.
AB  - Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC
      CMs) have emerged as a promising experimental tool for translational heart
      research and drug development. However, their usability as a human adult
      cardiomyocyte model is limited by their functional immaturity. Our aim is to
      analyse quantitatively those characteristics and how they differ from adult CMs.
      Methods and Results: We have developed a novel in silico model with all essential
      functional electrophysiology and calcium handling features of hiPSC-CMs.
      Importantly, the virtual cell recapitulates the immature intracellular ion
      dynamics that are characteristic for hiPSC-CMs, as quantified based our in vitro
      imaging data. The strong "calcium clock" is a source for a dual function of
      excitation-contraction coupling in hiPSC-CMs: action potential and calcium
      transient morphology vary substantially depending on the activation sequence of
      underlying ionic currents and fluxes that is altered in spontaneous vs. paced
      mode. Furthermore, parallel simulations with hiPSC-CM and adult cardiomyocyte
      models demonstrate the central differences. Results indicate that hiPSC-CMs
      translate poorly the disease specific phenotypes of Brugada syndrome, long QT
      Syndrome and catecholaminergic polymorphic ventricular tachycardia, showing less
      robustness and greater tendency for arrhythmic events than adult CMs. Based on a
      comparative sensitivity analysis, hiPSC-CMs share some features with adult CMs,
      but are still functionally closer to prenatal CMs than adult CMs. A database
      analysis of 3000 hiPSC-CM model variants suggests that hiPSC-CMs recapitulate
      poorly fundamental physiological properties of adult CMs. Single modifications do
      not appear to solve this problem, which is mostly contributed by the immaturity
      of intracellular calcium handling. Conclusion: Our data indicates that
      translation of findings from hiPSC-CMs to human disease should be made with great
      caution. Furthermore, we established a mathematical platform that can be used to
      improve the translation from hiPSC-CMs to human, and to quantitatively evaluate
      hiPSC-CMs development toward more general and valuable model for human cardiac
      diseases.

PMID- 29467679
TI  - The Endocannabinoid System across Postnatal Development in Transmembrane Domain
      Neuregulin 1 Mutant Mice.
AB  - The use of cannabis is a well-established component risk factor for
      schizophrenia, particularly in adolescent individuals with genetic predisposition
      for the disorder. Alterations to the endocannabinoid system have been found in
      the prefrontal cortex of patients with schizophrenia. Thus, we assessed whether
      molecular alterations exist in the endocannabinoid signalling pathway during
      brain development in a mouse model for the schizophrenia risk gene neuregulin 1
      (Nrg1). We analysed transcripts encoding key molecules of the endocannabinoid
      system in heterozygous transmembrane domain Nrg1 mutant mice (Nrg1 TM HET), which
      is known to have increased sensitivity to cannabis exposure. Tissue from the
      prelimbic cortex and hippocampus of male and female Nrg1 TM HET mice and wild
      type-like littermates was collected at postnatal days (PNDs) 7, 10, 14, 21, 28,
      35, 49, and 161. Quantitative polymerase chain reaction was conducted to assess
      mRNA levels of cannabinoid receptor 1 (CB1R) and enzymes for the synthesis and
      breakdown of the endocannabinoid 2-arachidonoylglycerol [i.e., diacylglycerol
      lipase alpha (DAGLalpha), monoglyceride lipase (MGLL), and alpha/beta-hydrolase
      domain-containing 6 (ABHD6)]. No sex differences were found for any transcripts
      in either brain region; thus, male and female data were pooled. Hippocampal and
      cortical mRNA expression of DAGLalpha, MGLL, and ABHD6 increased until PND 21-35
      and then decreased and stabilised for the rest of postnatal development.
      Hippocampal CB1R mRNA expression increased until PND 21 and decreased after this
      age. Expression levels of these endocannabinoid markers did not differ in Nrg1 TM
      HET compared to control mice at any time point. Here, we demonstrate dynamic
      changes in the developmental trajectory of several key endocannabinoid system
      transcripts in the mouse brain, which may correspond with periods of
      endocannabinoid system maturation. Nrg1 TM HET mutation did not alter the
      developmental trajectory of the endocannabinoid markers assessed, suggesting that
      other mechanisms may be responsible for the exaggerated cannabinoid
      susceptibility in these mice.

PMID- 29467680
TI  - Defining a Brief Intervention for the Promotion of Psychological Well-being among
      Unemployed Individuals through Expert Consensus.
AB  - Background: Epidemiologic evidence highlights the harmful consequences of
      unemployment on health and well-being. This emphasizes the need to design low
      cost interventions to prevent the adverse mental health effects of unemployment.
      The main aim of this study was to create expert-consensus regarding development
      and implementation of a brief, sustainable, and effective intervention program
      for promoting mental health among unemployed. Methods: The Delphi technique
      entailed a selected panel of 75 experts from various relevant professional
      backgrounds. Panel members were asked to state their level of agreement (5-point
      Likert scale) regarding (a) required characteristics for an effective mental
      health intervention for unemployed people and (b) key variables for assessing the
      effectiveness of that intervention. Consensus was obtained throughout two rounds
      of data collection through e-mail contact, with structured questionnaires. Items
      of the questionnaire were based on literature reviews about community-based
      interventions for unemployed individuals. Results: Overall, 46 experts
      collaborated with the Delphi process (final participation rate: 61.3%). Based on
      a review of the literature, 185 items were identified and grouped into two broad
      categories (set of characteristics of the intervention and set of variables for
      effectiveness assessment), aggregating a total of 11 dimensions. The two Delphi
      rounds resulted in the selection of 35 characteristic items for the intervention
      program and 54 variables for its effectiveness assessment. Brief group
      interventions were considered to be effective and sustainable for mental health
      promotion in unemployment conditions if targeting mental health literacy,
      training interpersonal skills, and job-search skills. Conclusion: As agreed by
      the panel of experts, a brief, sustainable and effective intervention can be
      developed and implemented by accounting for unemployed capacity-building for
      mental health self-care and adequate job-searching attitudes and skills. These
      results should be further implemented in community and multisector-based
      standardized interventions, targeting mental health among unemployed people,
      ensuring adequate conditions for its effectiveness assessment.

PMID- 29467682
TI  - Promoting Personal Growth through Experiential Learning: The Case of Expressive
      Arts Therapy for Lecturers in Thailand.
AB  - The aim of the paper is to assess academic experiential learning in relation to
      academic lectures' perceived personal and professional growth. Sixteen PhD
      students (age ranged between 23 and 46, 10 male, 6 females) participated in an
      introduction to expressive art therapy. Qualitative methods according to
      phenomenological methodology was used. At the beginning and end of the 48-h
      course they were asked to draw themselves, and explain the differences between
      the two drawings. In addition participants were semi-structured interviewed about
      the course and its personal and professional aspects at the end of the course.
      The main themes were the carousal of emotional experience, the use of art means
      for growth, and, professional growth. Findings revealed a perceived growth in
      terms of family relationships, inter-personal skills, and professional role
      performance.

PMID- 29467681
TI  - Glutamate Levels and Resting Cerebral Blood Flow in Anterior Cingulate Cortex Are
      Associated at Rest and Immediately Following Infusion of S-Ketamine in Healthy
      Volunteers.
AB  - Progressive loss of brain tissue is seen in some patients with schizophrenia and
      might be caused by increased levels of glutamate and resting cerebral blood flow
      (rCBF) alterations. Animal studies suggest that the normalisation of glutamate
      levels decreases rCBF and prevents structural changes in hippocampus. However,
      the relationship between glutamate and rCBF in anterior cingulate cortex (ACC) of
      humans has not been studied in the absence of antipsychotics and illness
      chronicity. Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist
      that transiently induces schizophrenia-like symptoms and neurobiological
      disturbances in healthy volunteers (HVs). Here, we used S-ketamine challenge to
      assess if glutamate levels were associated with rCBF in ACC in 25 male HVs.
      Second, we explored if S-ketamine changed the neural activity as reflected by
      rCBF alterations in thalamus (Thal) and accumbens that are connected with ACC.
      Glutamatergic metabolites were measured in ACC with magnetic resonance (MR)
      spectroscopy and whole-brain rCBF with pseudo-continuous arterial spin labelling
      on a 3-T MR scanner before, during, and after infusion of S-ketamine (total dose
      0.375 mg/kg). In ACC, glutamate levels were associated with rCBF before (p <
      0.05) and immediately following S-ketamine infusion (p = 0.03), but not during
      and after. S-Ketamine increased rCBF in ACC (p < 0.001) but not the levels of
      glutamate (p = 0.96). In subcortical regions, S-ketamine altered rCBF in left
      Thal (p = 0.03). Our results suggest that glutamate levels in ACC are associated
      with rCBF at rest and in the initial phase of an increase. Furthermore, S
      ketamine challenge transiently induces abnormal activation of ACC and left Thal
      that both are implicated in the pathophysiology of schizophrenia. Future
      longitudinal studies should investigate if increased glutamate and rCBF are
      related to the progressive loss of brain tissue in initially first-episode
      patients.

PMID- 29467683
TI  - Lacan and Adolescence: The Contemporary Clinic of the "Sexual Non-rapport" and
      Pornography.
AB  - This article explores two clinical phenomena-pornography and conspiracy thinking
      that are highly relevant today and can be observed specifically among adolescent
      boys in the early stages of post-puberty: conspiracy thinking and the viewing of
      pornographic videos. It shows that the Lacanian concepts of the Real (of puberty)
      and the sexual non-rapport help us understand the psychopathological aspects of
      these two phenomena. Watching pornographic material becomes equivalent to a
      conspiracy theory about the sexual non-rapport; both in fact deny the effect of
      what puberty introduces as radically new.

PMID- 29467684
TI  - Cognitive Remediation in Middle-Aged or Older Inpatients with Chronic
      Schizophrenia: A Randomized Controlled Trial in Korea.
AB  - Background: Accumulating evidence indicates that cognitive remediation (CR) is
      effective for improving various cognitive deficits in adult patients with
      schizophrenia. Although reports of brain plasticity in older adults and the
      service needs for chronic patients with schizophrenia are increasing, very few
      randomized controlled trials of CR have been conducted in middle-aged or older
      inpatients with chronic schizophrenia. We investigated the efficacy of
      individualized CR on the cognitive impairments of middle-aged or older inpatients
      with chronic schizophrenia within the context of comprehensive psychiatric
      rehabilitation (PR) by comparing the results obtained with PR only and treatment
      as usual (TAU). Method: Fifty-seven middle-aged and older individuals with
      chronic schizophrenia and mild to moderate cognitive deficits were enrolled.
      Thirty-eight who were undergoing PR were randomly assigned to CR + PR (N = 19) or
      PR-only (N = 19) groups. Nineteen participants who were undergoing TAU without CR
      or PR were evaluated pre- and post-treatment. Results: CR was easily provided and
      well received (drop-out rates = 5.3%) by middle-aged or older psychiatric
      inpatients. Compared to the PR-Only or TAU patients, patients in the CR + PR
      group showed greater improvement in executive functioning. Compared to TAU
      patients, CR + PR and PR-only patients showed greater improvement in logical
      memory. More patients in the CR + PR group improved clinically significantly in
      executive functioning and logical memory, compared with the PR-only and TAU
      patients. Conclusions: These results suggested that CR improved some cognitive
      deficits in middle-aged or older inpatients with chronic schizophrenia and that
      it was effective as an adjunctive treatment to the usual PR services provided in
      inpatient settings. Clinical Registration: KCT0002609.

PMID- 29467685
TI  - How Executive Functions Are Evaluated in Children and Adolescents with Cerebral
      Palsy? A Systematic Review.
AB  - Aims: The aim of the present study was to examine how executive functions are
      assessed in children and adolescents with Cerebral Palsy. Method: A systematic
      literature review was conducted using four bibliographic databases (WebScience,
      Scopus, PubMed, and Psycinfo), and only studies that evaluated at least one
      executive function were selected. Both the research and reporting of results were
      based on Cochrane's recommendations and PRISMA (Preferred Reporting Items for
      Systematic Reviews and Meta-Analysis) guidelines. Results: The instrument most
      frequently used was the D-KEFS. All studies point to the existence of impairments
      in the executive functions among children and adolescents with Cerebral Palsy
      with an impact on several cognitive and life domains. Interpretation: There is a
      need to further systematize the research protocols to study the executive
      functions and their assessment in the intervention context. Findings of this
      review presented a diversity of tests (e.g., D-KEFS) or tasks (e.g., The
      inhibitory ability task) used with children with Cerebral Palsy. However, no
      information was given about adaptations performed to the test/task to meet
      Cerebral Palsy's specificities. Future research could consider including this
      information, which is key both to researchers and practitioners. The results of
      this study have important implications and suggestions for future avenues and
      guidelines for research and practice.

PMID- 29467686
TI  - The Role of Personality in Daily Food Allergy Experiences.
AB  - Food allergies present numerous challenges to coping in everyday life. Even
      simple things like planning a lunch with a friend can be stressful for people
      with food allergies. But are some people more adversely impacted by having a food
      allergy than other people? This paper addressed this question by investigating
      whether individual differences in the Big Five personality traits (neuroticism,
      extraversion, openness, agreeableness, and conscientiousness) are related to food
      allergy-related problems in everyday life among adults with food allergies.
      Participants were 108 adults (85% female; mean age = 40.2; age range 18-87) with
      a physician-diagnosed food allergy [most commonly to gluten (54.6%), peanuts
      (21.3%), cow's milk (16.7%), and shellfish/seafood (16.7%)]. Participants
      completed an initial online survey that measured demographics, food allergy
      information, and personality traits using the Big Five Inventory (John et al.,
      1991). For 2 weeks, participants completed a daily online survey that queried the
      occurrence of 25 food allergy issues that day and participants' overall stress
      and mood that day. Neuroticism did not predict more frequent allergy issues or
      greater stress/poorer mood on days with more allergy issues. Instead, higher
      openness to experience predicted a range of issues including going hungry because
      there is no safe food available, problems finding suitable foods when grocery
      shopping, feeling anxious at social occasions involving food, being excluded, and
      feeling embarrassed and poorly understood about their food allergy. Conscientious
      people were less embarrassed or self-conscious about their food allergy, but they
      had more problems eating out, and their positive mood was more impaired by
      allergy issues than their less conscientious peers. Extraversion and
      agreeableness played minor roles. Personality testing can identify people that
      may have difficulty living with food allergies-such as those higher in openness
      to experience.

PMID- 29467687
TI  - "Homework Feedback Is...": Elementary and Middle School Teachers' Conceptions of
      Homework Feedback.
AB  - This study explored mathematics teachers' conceptions of the homework feedback
      focusing on four key aspects: definition, purpose, types, and perceived impact.
      Forty-seven teachers from elementary and middle schools participated in six focus
      groups. Data were analyzed using content analysis. To enhance the trustworthiness
      of findings, classroom observations were used for triangulation of data.
      Participants conceptualized homework feedback in three directions (i.e.,
      teachers' feedback provided to students, students' feedback provided to teachers,
      and homework self-feedback), being teachers' monitoring of students' learning the
      purpose reported by most teachers. Participants also reported the types of
      homework feedback more frequently used in class (e.g., checking homework
      completion, checking homework on the board), and their perceived impact on
      students. Findings provide valuable information to deepen the understanding of
      the homework feedback process, which may help develop new avenues for future
      research.

PMID- 29467688
TI  - Editorial: Post-traumatic Stress in the Family.

PMID- 29467689
TI  - Sociality Mental Modes Modulate the Processing of Advice-Giving: An Event-Related
      Potentials Study.
AB  - People have different motivations to get along with others in different sociality
      mental modes (i.e., communal mode and market mode), which might affect social
      decision-making. The present study examined how these two types of sociality
      mental modes affect the processing of advice-giving using the event-related
      potentials (ERPs). After primed with the communal mode and market mode,
      participants were instructed to decide whether or not give an advice (profitable
      or damnous) to a stranger without any feedback. The behavioral results showed
      that participants preferred to give the profitable advice to the stranger more
      slowly compared with the damnous advice, but this difference was only observed in
      the market mode condition. The ERP results indicated that participants
      demonstrated more negative N1 amplitude for the damnous advice compared with the
      profitable advice, and larger P300 was elicited in the market mode relative to
      both the communal mode and the control group. More importantly, participants in
      the market mode demonstrated larger P300 for the profitable advice than the
      damnous advice, whereas this difference was not observed at the communal mode and
      the control group. These findings are consistent with the dual-process system
      during decision-making and suggest that market mode may lead to deliberate
      calculation for costs and benefits when giving the profitable advice to others.

PMID- 29467690
TI  - The Role of Book Features in Young Children's Transfer of Information from
      Picture Books to Real-World Contexts.
AB  - Picture books are an important source of new language, concepts, and lessons for
      young children. A large body of research has documented the nature of parent
      child interactions during shared book reading. A new body of research has begun
      to investigate the features of picture books that support children's learning and
      transfer of that information to the real world. In this paper, we discuss how
      children's symbolic development, analogical reasoning, and reasoning about
      fantasy may constrain their ability to take away content information from picture
      books. We then review the nascent body of findings that has focused on the impact
      of picture book features on children's learning and transfer of words and
      letters, science concepts, problem solutions, and morals from picture books. In
      each domain of learning we discuss how children's development may interact with
      book features to impact their learning. We conclude that children's ability to
      learn and transfer content from picture books can be disrupted by some book
      features and research should directly examine the interaction between children's
      developing abilities and book characteristics on children's learning.

PMID- 29467692
TI  - Actively Coping with Violation: Exploring Upward Dissent Patterns in Functional,
      Dysfunctional, and Deserted Psychological Contract End States.
AB  - Recently, scholars have emphasized the importance of examining how employees cope
      with psychological contract violation and how the coping process contributes to
      psychological contract violation resolution and post-violation psychological
      contracts. Recent work points to the important role of problem-focused coping.
      Yet, to date, problem-focused coping strategies have not been conceptualized on a
      continuum from constructive to destructive strategies. Consequently, potential
      differences in the use of specific types of problem-focused coping strategies and
      the role these different strategies play in the violation resolution process has
      not been explored. In this study, we stress the importance of focusing on
      different types of problem-focused coping strategies. We explore how employee
      upward dissent strategies, conceptualized as different forms of problem-focused
      coping, contribute to violation resolution and post-violation psychological
      contracts. Two sources of data were used. In-depth interviews with supervisors of
      a Dutch car lease company provided 23 case descriptions of employee-supervisor
      interactions after a psychological contract violation. Moreover, a database with
      descriptions of Dutch court sentences provided eight case descriptions of
      employee-organization interactions following a perceived violation. Based on
      these data sources, we explored the pattern of upward dissent strategies
      employees used over time following a perceived violation. We distinguished
      between functional (thriving and reactivation), dysfunctional (impairment and
      dissolution) and deserted psychological contract end states and explored whether
      different dissent patterns over time differentially contributed to the dissent
      outcome (i.e., psychological contract end state). The results of our study showed
      that the use of problem-focused coping is not as straightforward as suggested by
      the post-violation model. While the post-violation model suggests that problem
      focused coping will most likely contribute positively to violation resolution, we
      found that this also depends on the type of problem-focused coping strategy used.
      That is, more threatening forms of problem-focused coping (i.e., threatening
      resignation as a way to trigger one's manager/organization to resolve the
      violation) mainly contributed to dysfunctional and deserted PC end states. Yet,
      in some instances the use of these types of active coping strategies also
      contributed to functional violation resolution. These findings have important
      implications for the literature on upward dissent strategies and psychological
      contract violation repair.

PMID- 29467691
TI  - Neural Correlates of Facial Mimicry: Simultaneous Measurements of EMG and BOLD
      Responses during Perception of Dynamic Compared to Static Facial Expressions.
AB  - Facial mimicry (FM) is an automatic response to imitate the facial expressions of
      others. However, neural correlates of the phenomenon are as yet not well
      established. We investigated this issue using simultaneously recorded EMG and
      BOLD signals during perception of dynamic and static emotional facial expressions
      of happiness and anger. During display presentations, BOLD signals and
      zygomaticus major (ZM), corrugator supercilii (CS) and orbicularis oculi (OO) EMG
      responses were recorded simultaneously from 46 healthy individuals. Subjects
      reacted spontaneously to happy facial expressions with increased EMG activity in
      ZM and OO muscles and decreased CS activity, which was interpreted as FM. Facial
      muscle responses correlated with BOLD activity in regions associated with motor
      simulation of facial expressions [i.e., inferior frontal gyrus, a classical
      Mirror Neuron System (MNS)]. Further, we also found correlations for regions
      associated with emotional processing (i.e., insula, part of the extended MNS). It
      is concluded that FM involves both motor and emotional brain structures,
      especially during perception of natural emotional expressions.

PMID- 29467693
TI  - Sensorimotor Learning during a Marksmanship Task in Immersive Virtual Reality.
AB  - Sensorimotor learning refers to improvements that occur through practice in the
      performance of sensory-guided motor behaviors. Leveraging novel technical
      capabilities of an immersive virtual environment, we probed the component
      kinematic processes that mediate sensorimotor learning. Twenty naive subjects
      performed a simulated marksmanship task modeled after Olympic Trap Shooting
      standards. We measured movement kinematics and shooting performance as
      participants practiced 350 trials while receiving trial-by-trial feedback about
      shooting success. Spatiotemporal analysis of motion tracking elucidated the
      ballistic and refinement phases of hand movements. We found systematic changes in
      movement kinematics that accompanied improvements in shot accuracy during
      training, though reaction and response times did not change over blocks. In
      particular, we observed longer, slower, and more precise ballistic movements that
      replaced effort spent on corrections and refinement. Collectively, these results
      leverage developments in immersive virtual reality technology to quantify and
      compare the kinematics of movement during early learning of full-body
      sensorimotor orienting.

PMID- 29467694
TI  - A New Look at the Impact of Maximizing on Unhappiness: Two Competing Mediating
      Effects.
AB  - The current study aims to explore how the decision-making style of maximizing
      affects subjective well-being (SWB), which mainly focuses on the confirmation of
      the mediator role of regret and suppressing role of achievement motivation. A
      total of 402 Chinese undergraduate students participated in this study, in which
      they responded to the maximization, regret, and achievement motivation scales and
      SWB measures. Results suggested that maximizing significantly predicted SWB.
      Moreover, regret and achievement motivation (hope for success dimension) could
      completely mediate and suppress this effect. That is, two competing indirect
      pathways exist between maximizing and SWB. One pathway is through regret.
      Maximizing typically leads one to regret, which could negatively predict SWB.
      Alternatively, maximizing could lead to high levels of hope for success, which
      were positively correlated with SWB. Findings offered a complex method of
      thinking about the relationship between maximizing and SWB.

PMID- 29467695
TI  - Returning to Work after Childbirth in Europe: Well-Being, Work-Life Balance, and
      the Interplay of Supervisor Support.
AB  - Parents returning to work after the arrival of a new son or daughter is an
      important question for understanding the trajectory of people's lives and
      professional careers amid current debates about gender equality and work-life
      balance (WLB). Interestingly, current research concludes that general WLB
      practices at the workplace may be necessary in the specific case of women
      returning to work after childbirth because of the particular maternal and infant
      factors involved. However, WLB practices as a flexible arrangement may work
      against women because they may be viewed as a lack of organizational commitment.
      Therefore, research on this topic could benefit from considering supervisor
      support as a complement of such practices, but previous research has analyzed WLB
      and supervisor support separately and scarcely. To fill this gap in the
      literature, we use two sub-samples of 664 female employees and 749 male employees
      with children under the age of one from 27 European countries participating in
      the 6th European Working Conditions Survey (EWCS-2015) to study the impact of
      perceived WLB on European women's perceived well-being after childbirth, in
      contrast with previous literature. We also analyze the impact of perceived
      supervisor support (SS) and its interaction with perceived WLB on women's well
      being after childbirth, and explore differences with men after childbirth, a
      collective underexplored by the literature. We find significant gender
      differences on the relative impact of WLB, SS, and their interaction on perceived
      job well-being. Our results have important implications for human resource
      practices in organizations. In particular, they suggest that gendered WLB
      practices should be encouraged, and stress the relevance of the human factor over
      human resource practices in addressing the difficulties that women returning to
      work face after childbirth.

PMID- 29467696
TI  - Attentional Bias to Beauty with Evolutionary Benefits: Evidence from Aesthetic
      Appraisal of Landscape Architecture.
AB  - Substantial evidence suggests that beauty is associated with the survival and
      reproduction of organisms. Landscape architecture is composed of a series of
      natural elements that have significant evolutionary implications. The present
      study used one pilot material ratings and three experiments to examine the
      mechanisms of aesthetic appraisals of landscape architecture. The results
      confirmed that landscape architecture elicited a sense of beauty and captured
      visual attention more easily than other types of architecture during explicit
      aesthetic rating task (Experiment 1) and implicit aesthetic perception task (dot
      probe paradigm, Experiment 2). Furthermore, the spatial cueing paradigm revealed
      that response latencies were significantly faster for landscape architecture than
      non-landscape architecture on valid trials, but there was no significant
      difference in this contrast on invalid trials at 150-ms stimulus onset asynchrony
      (SOA, Experiment 3a). At 500-ms SOA (Experiment 3b), participants responded
      significantly faster for landscape architecture on valid trials, but reacted
      significantly slower for landscape architecture on invalid trials. The findings
      indicated that the beauty of landscape architecture can be perceived implicitly,
      and only faster orienting of attention, but not delayed disengagement of
      attention was generated at early stages of the processing of landscape
      architecture. However, the attentional bias at later stages of attentional
      processes may be resulted from both faster orienting of attention and delayed
      disengagement of attention from landscape architecture photographs.

PMID- 29467697
TI  - Disgust, Sadness, and Appraisal: Disgusted Consumers Dislike Food More Than Sad
      Ones.
AB  - According to the affect-as-information framework, consumers base judgments on
      their feelings. Disgust is associated with two kinds of appraisal: one in which
      the consumer avoids and distances him/herself immediately from the object
      concerned, and another in which the consumer is disgusted due to contamination
      and impurities within the environment. The first instance indicates that disgust
      can decrease a consumer's preference for a product, regardless of its category.
      In contrast, the second case suggests that a product's degree of depreciation is
      greater in products vulnerable to contamination, such as foods. However, it
      remains largely unknown how incidental disgust affects product preferences in
      accordance with the two appraisal-related goals. The present research
      investigates how incidental disgust (as opposed to sadness, an equally valenced
      but distinct emotion of appraisal) influences consumer preferences for products
      with or without a risk of contamination. Twenty-four participants repeatedly
      judged foods or household products after seeing an emotional image (conveying
      disgust, sadness, or neutrality). Foods and household products are the two
      representative product categories in grocery stores, but only foods are
      associated with a risk of contamination. The results showed that incidental
      disgust led to negative evaluations of both types of products; however, compared
      to sadness, incidental disgust demonstrated a stronger negative effect on
      preference for foods than household products. These findings elucidate that
      disgust and the appraisal of contamination specifically devalue foods, and
      broaden the application of the appraisal-information framework in consumer
      settings.

PMID- 29467698
TI  - Dual Systems for Spatial Updating in Immediate and Retrieved Environments:
      Evidence from Bias Analysis.
AB  - The spatial updating and memory systems are employed during updating in both the
      immediate and retrieved environments. However, these dual systems seem to work
      differently, as the difference of pointing latency and absolute error between the
      two systems vary across environments. To verify this issue, the present study
      employed the bias analysis of signed errors based on the hypothesis that the
      transformed representation will bias toward the original one. Participants
      learned a spatial layout and then either stayed in the learning location or were
      transferred to a neighboring room directly or after being disoriented. After
      that, they performed spatial judgments from perspectives aligned with the
      learning direction, aligned with the direction they faced during the test, or a
      novel direction misaligned with the two above-mentioned directions. The patterns
      of signed error bias were consistent across environments. Responses for memory
      aligned perspectives were unbiased, whereas responses for sensorimotor aligned
      perspectives were biased away from the memory aligned perspective, and responses
      for misaligned perspectives were biased toward sensorimotor aligned perspectives.
      These findings indicate that the spatial updating system is consistently
      independent of the spatial memory system regardless of the environments, but the
      updating system becomes less accessible as the environment changes from immediate
      to a retrieved one.

PMID- 29467699
TI  - When Project Commitment Leads to Learning from Failure: The Roles of Perceived
      Shame and Personal Control.
AB  - Facing a remarkably changing world, researchers have gradually shifted emphasis
      from successful experiences to failures. In the current study, we build a model
      to explore the relationship between project commitment and learning from failure,
      and test how emotion (i.e., perceived shame after failure) and cognition (i.e.,
      attribution for failure) affect this process. After randomly selecting 400 firms
      from the list of high-tech firms reported by the Beijing Municipal Science and
      Technology Commission, we use a two-wave investigation of the employees, and the
      final sample consists of 140 teams from 58 companies in the technology industry
      in mainland China. The results provide evidence for the positive role of personal
      control attribution in the relationship between project commitment and learning
      from failure. However, in contrast to previous studies, perceived shame, as the
      negative emotion after failed events, could bring desirable outcomes during this
      process. Based on the results, we further expand a model to explain the
      behavioral responses after failure, and the implications of our findings for
      research and practice are discussed. The failures and reverses which await men -
      and one after another sadden the brow of youth - add a dignity to the prospect of
      human life, which no Arcadian success would do. -Henry David Thoreau.

PMID- 29467700
TI  - Development and Preliminary Validation of the Salzburg Emotional Eating Scale.
AB  - Existing self-report questionnaires for the assessment of emotional eating do not
      differentiate between specific types of emotions and between increased or
      decreased food intake in response to these emotions. Therefore, we developed a
      new measure of emotional eating-the Salzburg Emotional Eating Scale (SEES)-for
      which higher scores indicate eating more than usual in response to emotions and
      lower scores indicate eating less than usual in response to emotions. In study 1,
      a pool of items describing 40 emotional states was used. Factor analysis yielded
      four factors, which represented both positive (happiness subscale) and negative
      emotions (sadness, anger, and anxiety subscales). Subsequently, the scale was
      reduced to 20 items (5 items for each subscale) and its four-factor structure was
      replicated in studies 2 and 3. In all three studies, internal consistencies of
      each subscale were alpha > 0.70 and mean subscale scores significantly differed
      from each other such that individuals reported the strongest tendency to eat more
      than usual when being sad and the strongest tendency to eat less than usual when
      being anxious (sadness > happiness > anger > anxiety). Higher scores on the
      happiness subscale related to lower scores on the negative emotions subscales,
      lower body mass index (BMI), and lower eating pathology. In contrast, higher
      scores on the negative emotions subscales related to lower scores on the
      happiness subscale, higher BMI, and higher eating pathology. The SEES represents
      a useful measure for the investigation of emotional eating by increasing both
      specificity (differentiation between specific emotional states) and breadth
      (differentiation between increase and decrease of food intake) in the assessment
      of the emotion-eating relationship.

PMID- 29467701
TI  - Are Expectations the Missing Link between Life History Strategies and
      Psychopathology?
AB  - Despite advances in knowledge and thinking about using life history theory to
      explain psychopathology there is still a missing link. That is, we all have a
      life history strategy, but not all of us develop mental health problems. We
      propose that the missing link is expectations - a mismatch between expected
      environmental conditions (including social) set by variations in life history
      strategies and the current environmental conditions. The mismatch hypothesis has
      been applied at the biological level in terms of health and disease and we
      believe that it can also be applied more broadly at the psychological level in
      terms of perceived expectations in the social environment and the resulting
      distress-psychopathology-that manifests when our expectations are not met.

PMID- 29467702
TI  - Are Leadership Fairness, Psychological Distress, and Role Stressors Interrelated?
      A Two-Wave Prospective Study of Forward and Reverse Relationships.
AB  - While previous research has mainly considered leadership as an antecedent to
      psychological distress and role stressors (i.e., role ambiguity and role
      conflict) among subordinates, a reverse relationship where these variables
      influence reports of leadership is also possible. To determine the directionality
      of the associations this two-wave prospective study assesses bidirectional
      relationships between fair leadership and role stressors and examines whether
      psychological distress mediates the reciprocal associations between fair
      leadership and the role stressors. Analyses were conducted in a sample of 6,790
      Norwegian employees with a 2-year time-lag between measurement points. Fair
      leadership was associated with lower stability adjusted role ambiguity, but not
      role conflict, over time. Role conflict, but not role ambiguity, was related to
      subsequent reports of the immediate leader as less fair. Psychological distress
      did neither mediate the relationship between fair leadership and subsequent
      reports of role stressors, nor the association between role stressors and
      subsequent reports of fair leadership. The findings suggest that the fair
      leadership - role stressor association is not a one-directional process, but that
      exposure to role stressors also influence subordinates' perceptions of
      leadership. An implication of the findings is that theoretical models of
      organizational leadership should include this reverse impact of role stressors.
      To reduce the effects of role stressors, organizations could set consistent,
      clear and attractive goals and provide employees with necessary information for
      conducting their work tasks in order to help workers understand and master their
      roles at the workplace.

PMID- 29467703
TI  - The Effect of Eye Contact Is Contingent on Visual Awareness.
AB  - The present study explored how eye contact at different levels of visual
      awareness influences gaze-induced joint attention. We adopted a spatial-cueing
      paradigm, in which an averted gaze was used as an uninformative central cue for a
      joint-attention task. Prior to the onset of the averted-gaze cue, either
      supraliminal (Experiment 1) or subliminal (Experiment 2) eye contact was
      presented. The results revealed a larger subsequent gaze-cueing effect following
      supraliminal eye contact compared to a no-contact condition. In contrast, the
      gaze-cueing effect was smaller in the subliminal eye-contact condition than in
      the no-contact condition. These findings suggest that the facilitation effect of
      eye contact on coordinating social attention depends on visual awareness.
      Furthermore, subliminal eye contact might have an impact on subsequent social
      attention processes that differ from supraliminal eye contact. This study
      highlights the need to further investigate the role of eye contact in implicit
      social cognition.

PMID- 29467704
TI  - Father-Child Longitudinal Relationship: Parental Monitoring and Internet Gaming
      Disorder in Chinese Adolescents.
AB  - Although empirical studies have indicated that parents have an important role in
      preventing Internet gaming disorder in adolescents, longitudinal research on the
      parental predictors of Internet gaming disorder is lacking. We used a three-wave
      cross-lagged panel model to explore the reciprocal association between parental
      monitoring and Internet gaming disorder, and examined the different impacts of
      mother- and father-child relationships on this association. A sample of 1490
      adolescents aged 10-15 years (M = 12.03, SD = 1.59; 45.4% female) completed
      assessments at all three points. The cross-lagged model revealed that (a)
      parental monitoring at T1 predicted lower Internet gaming disorder at T2, and
      greater Internet gaming disorder at T2 predicted lower parental monitoring at T3;
      (b) father-child relationship had a reciprocal, indirect effect on the
      relationship between parental monitoring and Internet gaming disorder, while
      mother-child relationship did not. These findings suggest that the parental
      effects (e.g., higher parental monitoring and better father-child relationship)
      might play a vital role in preventing Internet gaming disorder in adolescents.

PMID- 29467705
TI  - Development and Validation of a Spanish Version of the Grit-S Scale.
AB  - This paper describes the development and initial validation of a Spanish version
      of the Short Grit (Grit-S) Scale. The Grit-S Scale was adapted and translated
      into Spanish using the Translation, Review, Adjudication, Pre-testing, and
      Documentation model and responses to a preliminary set of items from a large
      sample of university students (N = 1,129). The resultant measure was validated
      using data from a large stratified random sample of young adults (N = 1,826).
      Initial validation involved evaluating the internal consistency of the adapted
      scale and its subscales and comparing the factor structure of the adapted version
      to that of the original scale. The results were comparable to results from
      similar analyses of the English version of the scale. Although the internal
      consistency of the subscales was low, the internal consistency of the full scale
      was well-within the acceptable range. A two-factor model offered an acceptable
      account of the data; however, when a single correlated error involving two highly
      similar items was included, a single factor model fit the data very well. The
      results support the use of overall scores from the Spanish Grit-S Scale in future
      research.

PMID- 29467706
TI  - Opening the Implicit Leadership Theories' Black Box: An Experimental Approach
      with Conjoint Analysis.
AB  - Although research on implicit leadership theories (ILTs) has concentrated on
      determining which attributes define a leadership prototype, little attention has
      been paid to testing the relative importance of each of these attributes for
      individuals' leadership perceptions. Building on socio-cognitive theories of
      impression processes, we experimentally explore the formation of leadership
      perceptions based on the recognition of six key attributes in a series of three
      experimental studies comprising 566 US-based participants recruited online via
      Amazon Mechanical Turk. Our results show that while certain attributes play an
      important role in the leader categorization process, others are less relevant. We
      also demonstrate that some attributes' importance is contingent on the presence
      of other attributes and on the leadership schema type activated in respondents'
      minds. Consistent with the Leadership Categorization Theory, our findings support
      the premise that individuals cognitively hold a superordinate leadership
      prototype, which imposes constraints on their more basic level prototypes. We
      discuss the implications of these results for leadership theory and practice.

PMID- 29467707
TI  - Commentary: From the Phenomenology to the Mechanisms of Consciousness: Integrated
      Information Theory 3.0.

PMID- 29467708
TI  - Musical Scales in Tone Sequences Improve Temporal Accuracy.
AB  - Predicting the time of stimulus onset is a key component in perception. Previous
      investigations of perceived timing have focused on the effect of stimulus
      properties such as rhythm and temporal irregularity, but the influence of non
      temporal properties and their role in predicting stimulus timing has not been
      exhaustively considered. The present study aims to understand how a non-temporal
      pattern in a sequence of regularly timed stimuli could improve or bias the
      detection of temporal deviations. We presented interspersed sequences of 3, 4, 5,
      and 6 auditory tones where only the timing of the last stimulus could slightly
      deviate from isochrony. Participants reported whether the last tone was 'earlier'
      or 'later' relative to the expected regular timing. In two conditions, the tones
      composing the sequence were either organized into musical scales or they were
      random tones. In one experiment, all sequences ended with the same tone; in the
      other experiment, each sequence ended with a different tone. Results indicate
      higher discriminability of anisochrony with musical scales and with longer
      sequences, irrespective of the knowledge of the final tone. Such an outcome
      suggests that the predictability of non-temporal properties, as enabled by the
      musical scale pattern, can be a factor in determining the sensitivity of time
      judgments.

PMID- 29467710
TI  - Structural Covariance Network of Cortical Gyrification in Benign Childhood
      Epilepsy with Centrotemporal Spikes.
AB  - Benign childhood epilepsy with centrotemporal spikes (BECTS) is associated with
      cognitive and language problems. According to recent studies, disruptions in
      brain structure and function in children with BECTS are beyond a Rolandic focus,
      suggesting atypical cortical development. However, previous studies utilizing
      surface-based metrics (e.g., cortical gyrification) and their structural
      covariance networks at high resolution in children with BECTS are limited. Twenty
      six children with BECTS (15 males/11 females; 10.35 +/- 2.91 years) and 26
      demographically matched controls (15 males/11 females; 11.35 +/- 2.51 years) were
      included in this study and subjected to high-resolution structural brain MRI
      scans. The gyrification index was calculated, and structural brain networks were
      reconstructed based on the covariance of the cortical folding. In the BECTS
      group, significantly increased gyrification was observed in the bilateral Sylvain
      fissures and the left pars triangularis, temporal, rostral middle frontal,
      lateral orbitofrontal, and supramarginal areas (cluster-corrected p < 0.05).
      Global brain network measures were not significantly different between the
      groups; however, the nodal alterations were most pronounced in the insular,
      frontal, temporal, and occipital lobes (FDR corrected, p < 0.05). In children
      with BECTS, brain hubs increased in number and tended to shift to sensorimotor
      and temporal areas. Furthermore, we observed significantly positive relationships
      between the gyrification index and age (vertex p < 0.001, cluster-level
      correction) as well as duration of epilepsy (vertex p < 0.001, cluster-level
      correction). Our results suggest that BECTS may be a condition that features
      abnormal over-folding of the Sylvian fissures and uncoordinated development of
      structural wiring, disrupted nodal profiles of centrality, and shifted hub
      distribution, which potentially represents a neuroanatomical hallmark of BECTS in
      the developing brain.

PMID- 29467709
TI  - Delayed Latency of Postural Muscles of Individuals with Intellectual
      Disabilities.
AB  - Individuals with intellectual disabilities (ID) (50 < IQ < 79) show impaired
      motor and postural control, these impairments are highly related to falls and
      injuries. Recent studies demonstrated these impairments are related with fine and
      gross motor development, which are more strongly associated with cognition, and
      consequently language for individuals with ID than for without ID. Despite these
      studies, little is known about the structure and functioning of this population's
      spinal cord, which is highly involved in postural control. The aim of our study
      was to assess the latency of the reflex responses in postural muscles after
      unexpected lateral external perturbations, in individuals with intellectual
      disabilities compared to typically developed participants. We assessed 16
      participants with intellectual disabilities, 9 males and 7 females (aged 24.06 +/
      8.66 years) and 20 typical developed participants (CG), 11 females, 9 males,
      (aged 21.20+/-1.96 years). While the participants were in an upright standing
      position electromyography was used to collect data from M. obliquus externus
      abdominis (OE) muscles, which were activated by unpredictable perturbations
      applied by a servomotor on a hand-held grip, following the lateral external
      perturbation to the trunk. The intellectual disabilities group presented
      contralateral OE muscles latency of 85.71+/-27.24 ms, and CG group presented
      68.62+/-10.25 ms, no differences was found. Ipsilateral OE muscles latency also
      did not differs between the groups, ID group showed 96.60+/-30.20 ms and CG group
      showed 95.57+/-33.53 ms. Our study furthers the knowledge about the muscular
      activity of individuals with intellectual disabilities. The present experimental
      results may suggest unique spinal cord processing of individuals with
      intellectual disabilities when they are faced with unexpected lateral external
      perturbations.

PMID- 29467711
TI  - Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and
      Treatment.
AB  - Multiple sclerosis (MS) commonly causes eye movement abnormalities that may have
      a significant impact on patients' disability. Inflammatory demyelinating lesions,
      especially occurring in the posterior fossa, result in a wide range of disorders,
      spanning from acquired pendular nystagmus (APN) to internuclear ophthalmoplegia
      (INO), among the most common. As the control of eye movements is well understood
      in terms of anatomical substrate and underlying physiological network, studying
      ocular motor abnormalities in MS provides a unique opportunity to gain insights
      into mechanisms of disease. Quantitative measurement and modeling of eye movement
      disorders, such as INO, may lead to a better understanding of common symptoms
      encountered in MS, such as Uhthoff's phenomenon and fatigue. In turn, the
      pathophysiology of a range of eye movement abnormalities, such as APN, has been
      clarified based on correlation of experimental model with lesion localization by
      neuroimaging in MS. Eye movement disorders have the potential of being utilized
      as structural and functional biomarkers of early cognitive deficit, and possibly
      help in assessing disease status and progression, and to serve as platform and
      functional outcome to test novel therapeutic agents for MS. Knowledge of
      neuropharmacology applied to eye movement dysfunction has guided testing and use
      of a number of pharmacological agents to treat some eye movement disorders found
      in MS, such as APN and other forms of central nystagmus.

PMID- 29467712
TI  - Structured Reporting in Neuroradiology: Intracranial Tumors.
AB  - Purpose: The aim of this pilot study was to assess the clinical feasibility,
      diagnostic yield, advantages, and disadvantages of structured reporting for
      routine MRI-reading in patients with primary diagnosis of intracranial tumors as
      compared to traditional neuroradiological free text reporting. Methods: A
      structured MRI reporting template was developed covering pathological,
      anatomical, and functional aspects in an itemized fashion. Retrospectively, 60
      consecutive patients with first diagnosis of an intracranial tumor were selected
      from the radiology information system/PACS system. Structured reporting was
      performed by a senior neuroradiologist, blinded to clinical and radiological
      data. Reporting times were measured per patient. The diagnostic content was
      compared to free text reporting which was independently performed on the same MRI
      exams by two other neuroradiologists. The comparisons were categorized per item
      as: "congruent," "partially congruent," "incongruent," or "not mentioned in free
      style report." Results: Tumor-related items: congruent findings were found for
      all items (17/17) with congruence rates ranging between 98 and 39% per item. Four
      items achieved congruence rates >=90%, 5 items >80%, and 9 items >=70%. Partially
      congruent findings were found for all items in up to 50% per item. Incongruent
      findings were present in 7/17 items in up to 5% per item. Free text reports did
      not mention 12 of 17 items (range 7-43% per item). Non-tumor-related items,
      including brain atrophy, microangiopathy, vascular pathologies, and various
      extracranial pathologies, which were not mentioned in free-text reports between
      18 and 85% per item. Mean reporting time for structured reporting was 7:49 min
      (3:12-17:06 min). Conclusion: First results showed that expert structured
      reporting ensured reliable detection of all relevant brain pathologies along with
      reproducible documentation of all predefined diagnostic items, which was not
      always the case for free text reporting. A mean reporting time of 8 min per
      patient seems clinically feasible.

PMID- 29467713
TI  - Potential of Stem Cell-Based Therapy for Ischemic Stroke.
AB  - Ischemic stroke is one of the major health problems worldwide. The only FDA
      approved anti-thrombotic drug for acute ischemic stroke is the tissue plasminogen
      activator. Several studies have been devoted to assessing the therapeutic
      potential of different types of stem cells such as neural stem cells (NSCs),
      mesenchymal stem cells, embryonic stem cells, and human induced pluripotent stem
      cell-derived NSCs as treatments for ischemic stroke. The results of these studies
      are intriguing but many of them have presented conflicting results. Additionally,
      the mechanism(s) by which engrafted stem/progenitor cells exert their actions are
      to a large extent unknown. In this review, we will provide a synopsis of
      different preclinical and clinical studies related to the use of stem cell-based
      stroke therapy, and explore possible beneficial/detrimental outcomes associated
      with the use of different types of stem cells. Due to limited/short time window
      implemented in most of the recorded clinical trials about the use of stem cells
      as potential therapeutic intervention for stroke, further clinical trials
      evaluating the efficacy of the intervention in a longer time window after
      cellular engraftments are still needed.

PMID- 29467714
TI  - Brivaracetam in the Treatment of Patients with Epilepsy-First Clinical
      Experiences.
AB  - Objectives: To assess first clinical experiences with brivaracetam (BRV) in the
      treatment of epilepsies. Methods: Data on patients treated with BRV from February
      to December 2016 and with at least one clinical follow-up were collected from
      electronic patient records. Data on safety and efficacy were evaluated
      retrospectively. Results: In total, 93 patients were analyzed; 12 (12.9%)
      received BRV in monotherapy. The mean duration to follow-up was 4.85 months (MD =
      4 months; SD = 3.63). Fifty-seven patients had more than one seizure per month at
      baseline and had a follow-up of more than 4 weeks; the rate of >=50% responders
      was 35.1% (n = 20) in this group, of which five (8.8%) patients were newly
      seizure-free. In 50.5% (47/93), patients were switched from levetiracetam (LEV)
      to BRV, of which 43 (46.2%) were switched immediately. Adverse events (AE)
      occurred in 39.8%, with 22.6% experiencing behavioral and 25.8% experiencing non
      behavioral AE. LEV-related AE (LEV-AE) were significantly reduced by switching to
      BRV. The discontinuation of BRV was reported in 26/93 patients (28%); 10 of those
      were switched back to LEV with an observed reduction of AE in 70%. For clinical
      reasons, 12 patients received BRV in monotherapy, 75% were seizure-free, and
      previous LEV-AE improved in 6/9 patients. BRV-related AE occurred in 5/12 cases,
      and five patients discontinued BRV. Conclusion: BRV seems to be a safe, easy, and
      effective option in the treatment of patients with epilepsy, especially in the
      treatment of patients who have psychiatric comorbidities and might not be good
      candidates for LEV treatment. BRV broadens the therapeutic spectrum and
      facilitates personalized treatment.

PMID- 29467716
TI  - Tissue Is More Important than Time in Stroke Patients Being Assessed for
      Thrombolysis.
AB  - Aim: The relative prognostic importance of modern imaging profiles compared with
      standard clinical characteristics is uncertain in acute stroke patients. In this
      study, we aimed to compare baseline multimodal CT imaging measures with known
      clinical predictors of patient outcome at 3 months [modified Rankin scale (mRS)].
      Methods: We collected baseline, 24 h, and day 90 clinical and imaging data from
      acute ischemic stroke patients being assessed for thrombolytic therapy between
      2010 and 2015 at a single center as part of a retrospective analysis. Results:
      561 patients presenting within 4.5 h of ischemic stroke onset who were eligible
      for thrombolysis based on standard clinical criteria were assessed. Acute infarct
      core volume on CTP was the strongest univariate predictor of patient outcome (mRS
      0-2, R2 0.497, p < 0.001), followed by collateral grade (mRS 0-2, R2 0.281, p <
      0.001). The strongest baseline clinical predictor of outcome was National
      Institutes of Health Stroke Scale (NIHSS) (mRS 0-2, R2 = 0.203, p < 0.001). Time
      to treatment (mRS 0-2, R2 0.096, p = 0.01) and age (mRS 0-2, R2 0.027, p = 0.013)
      were relatively weak univariate baseline clinical predictors of 3-month outcome.
      In multivariate analysis, acute infarct core volume and collateral grade were the
      only significant baseline predictors of 3-month disability (both p < 0.001).
      Conclusion: In patients assessed for thrombolysis by combined clinical and
      multimodal CT criteria within 4.5 h of onset, the size of the CTP infarct core
      and collateral grade on multimodal CT were highly predictive of patient outcome.
      Standard clinical variables, including time to treatment and NIHSS, were not as
      strongly predictive as multimodal CT variables.

PMID- 29467715
TI  - Limb Remote Ischemic Conditioning: Mechanisms, Anesthetics, and the Potential for
      Expanding Therapeutic Options.
AB  - Novel and innovative approaches are essential in developing new treatments and
      improving clinical outcomes in patients with ischemic stroke. Remote ischemic
      conditioning (RIC) is a series of mechanical interruptions in blood flow of a
      distal organ, following end organ reperfusion, shown to significantly reduce
      infarct size through inhibition of oxidation and inflammation.
      Ischemia/reperfusion (I/R) is what ultimately leads to the irreversible brain
      damage and clinical picture seen in stroke patients. There have been several
      reports and reviews about the potential of RIC in acute ischemic stroke; however,
      the focus here is a comprehensive look at the differences in the three types of
      RIC (remote pre-, per-, and postconditioning). There are some limited uses of
      preconditioning in acute ischemic stroke due to the unpredictability of the
      ischemic event; however, it does provide the identification of biomarkers for
      clinical studies. Remote limb per- and postconditioning offer a more promising
      treatment during patient care as they can be harnessed during or after the
      initial ischemic insult. Though further research is needed, it is imperative to
      discuss the importance of preclinical data in understanding the methods and
      mechanisms involved in RIC. This understanding will facilitate translation to a
      clinically feasible paradigm for use in the hospital setting.

PMID- 29467717
TI  - Thioredoxin-1 Protects Spinal Cord from Demyelination Induced by Methamphetamine
      through Suppressing Endoplasmic Reticulum Stress and Inflammation.
AB  - Methamphetamine (METH) is a psychostimulant abused around the world. Emerging
      evidence indicates that METH causes brain damage. However, there are very few
      reports on METH-induced demyelination. Thioredoxin-1 (Trx-1) is a redox
      regulating protein and plays the roles in protecting neurons from various
      stresses. However, whether Trx-1 resists demyelination induced by METH has not
      been reported. In this study, we found that METH-induced thin myelin sheaths in
      spinal cord, whereas Trx-1 overexpression transgenic (TG) mice restored the
      myelin sheaths thickness. The expressions of myelin-associated glycoprotein,
      myelin basic protein, and cyclin-dependent kinase 5 were decreased by METH,
      whereas these alterations were blocked in Trx-1 TG mice. The expressions of
      procaspase-12 and procaspase-3 were decreased by METH, the expression of calpain1
      was increased by METH, whereas the alterations were suppressed in Trx-1 TG mice.
      As same as, the expressions of the extracellular signal-regulated kinase, nuclear
      factor kappaB, tumor necrosis factor-alpha, and interleukin-1beta were induced by
      METH, which were suppressed in Trx-1 TG mice. These data suggest that Trx-1 may
      play a critical role in resisting the METH-mediated demyelination in spinal cord
      through regulating endoplasmic reticulum stress and inflammation pathways.

PMID- 29467718
TI  - On the Accurate Determination of Shock Wave Time-Pressure Profile in the
      Experimental Models of Blast-Induced Neurotrauma.
AB  - Measurement issues leading to the acquisition of artifact-free shock wave
      pressure-time profiles are discussed. We address the importance of in-house
      sensor calibration and data acquisition sampling rate. Sensor calibration takes
      into account possible differences between calibration methodology in a
      manufacturing facility, and those used in the specific laboratory. We found in
      house calibration factors of brand new sensors differ by less than 10% from their
      manufacturer supplied data. Larger differences were noticeable for sensors that
      have been used for hundreds of experiments and were as high as 30% for sensors
      close to the end of their useful lifetime. These observations were despite the
      fact that typical overpressures in our experiments do not exceed 50 psi for
      sensors that are rated at 1,000 psi maximum pressure. We demonstrate that
      sampling rate of 1,000 kHz is necessary to capture the correct rise time values,
      but there were no statistically significant differences between peak overpressure
      and impulse values for low-intensity shock waves (Mach number <2) at lower rates.
      We discuss two sources of experimental errors originating from mechanical
      vibration and electromagnetic interference on the quality of a waveform recorded
      using state-of-the-art high-frequency pressure sensors. The implementation of
      preventive measures, pressure acquisition artifacts, and data interpretation with
      examples, are provided in this paper that will help the community at large to
      avoid these mistakes. In order to facilitate inter-laboratory data comparison,
      common reporting standards should be developed by the blast TBI research
      community. We noticed the majority of published literature on the subject limits
      reporting to peak overpressure; with much less attention directed toward other
      important parameters, i.e., duration, impulse, and dynamic pressure. These
      parameters should be included as a mandatory requirement in publications so the
      results can be properly compared with others.

PMID- 29467720
TI  - The Steroid Hormone 20-Hydroxyecdysone Regulates the Conjugation of Autophagy
      Related Proteins 12 and 5 in a Concentration and Time-Dependent Manner to Promote
      Insect Midgut Programmed Cell Death.
AB  - Autophagy requires the conjugation of autophagy-related protein 12 (ATG12) to
      autophagy-related protein 5 (ATG5) through covalent attachment. However, the
      signals regulating ATG12-ATG5 conjugation are unclear. The larval midgut of
      lepidopteran insects performs autophagy and apoptosis sequentially during the
      transition of larvae to pupae under regulation by the steroid hormone 20
      hydroxyecdysone (20E), thus representing a model to study steroid hormone
      regulation of ATG12-ATG5 conjugation. In the present study, using the
      lepidopteran insect Helicoverpa armigera as a model, we report that 20E regulates
      the conjugation of ATG12-ATG5 in a concentration and time-dependent manner. The
      ATG12-ATG5 conjugate was abundant in the epidermis, midgut, and fat body during
      metamorphosis from the larvae to the pupae; however, the ATG12-ATG5 conjugate
      level decreased at the time of pupation. At low concentrations (2-5 uM) over a
      short time course (1-48 h), 20E promoted the conjugation of ATG12-ATG5; however,
      at 10 uM and 72 h, 20E repressed the conjugation of ATG12-ATG5. ATG12 was
      localized in the larval midgut during metamorphosis. Knockdown of ATG12 in larvae
      caused death with delayed pupation, postponed the process of midgut programmed
      cell death (PCD), and repressed ATG8 (also called LC3-I) transformation to LC3-II
      and the cleavage of caspase-3; therefore, knockdown of ATG12 in larvae blocked
      both autophagy and apoptosis. Knockdown of ATG12 in H. armigera epidermis cell
      line cells also repressed 20E-induced autophagosome formation and caspase-3
      activation. The results suggested that 20E plays key role in the regulation of
      ATG12-ATG5 conjugation in a concentration and time-dependent manner for autophagy
      or apoptosis, and that ATG12 is necessary by both autophagy and apoptosis during
      insect midgut PCD.

PMID- 29467719
TI  - Physical Exercise Enhanced Heat Shock Protein 60 Expression and Attenuated
      Inflammation in the Adipose Tissue of Human Diabetic Obese.
AB  - Heat shock protein 60 (HSP60) is a key protein in the crosstalk between cellular
      stress and inflammation. However, the status of HSP60 in diabetes and obesity is
      unclear. In the present study, we investigated the hypothesis that HSP60
      expression levels in the adipose tissue of human obese adults with and without
      diabetes are different and physical exercise might affect these levels.
      Subcutaneous adipose tissue (SAT) and blood samples were collected from obese
      adults with and without diabetes (n = 138 and n = 92, respectively, at baseline;
      n = 43 for both groups after 3 months of physical exercise). Conventional RT-PCR,
      immunohistochemistry, immunofluorescence, and ELISA were used to assess the
      expression and secretion of HSP60. Compared with obese adults without diabetes,
      HSP60 mRNA and protein levels were decreased in SAT in diabetic obese together
      with increased inflammatory marker expression and glycemic levels but lower VO2
      Max. More interestingly, a 3-month physical exercise differentially affected
      HSP60 expression and the heat shock response but attenuated inflammation in both
      groups, as reflected by decreased endogenous levels of IL-6 and TNF-alpha.
      Indeed, HSP60 expression levels in SAT were significantly increased by exercise
      in the diabetes group, whereas they were decreased in the non-diabetes group.
      These results were further confirmed using immunofluorescence microscopy and anti
      HSP60 antibody in SAT. Exercise had only marginal effects on HSP60 secretion and
      HSP60 autoantibody levels in plasma in both obese with and without diabetes.
      Physical exercise differentially alleviates cellular stress in obese adults with
      and without diabetes despite concomitant attenuation of the inflammatory
      response.

PMID- 29467721
TI  - A Microfluidics and Agent-Based Modeling Framework for Investigating Spatial
      Organization in Bacterial Colonies: The Case of Pseudomonas Aeruginosa and H1
      Type VI Secretion Interactions.
AB  - The factors leading to changes in the organization of microbial assemblages at
      fine spatial scales are not well characterized or understood. However, they are
      expected to guide the succession of community development and function toward
      specific outcomes that could impact human health and the environment. In this
      study, we put forward a combined experimental and agent-based modeling framework
      and use it to interpret unique spatial organization patterns of H1-Type VI
      secretion system (T6SS) mutants of P. aeruginosa under spatial confinement. We
      find that key parameters, such as T6SS-mediated cell contact and lysis, spatial
      localization, relative species abundance, cell density and local concentrations
      of growth substrates and metabolites are influenced by spatial confinement. The
      model, written in the accessible programming language NetLogo, can be adapted to
      a variety of biological systems of interest and used to simulate experiments
      across a broad parameter space. It was implemented and run in a high-throughput
      mode by deploying it across multiple CPUs, with each simulation representing an
      individual well within a high-throughput microwell array experimental platform.
      The microfluidics and agent-based modeling framework we present in this paper
      provides an effective means by which to connect experimental studies in
      microbiology to model development. The work demonstrates progress in coupling
      experimental results to simulation while also highlighting potential sources of
      discrepancies between real-world experiments and idealized models.

PMID- 29467723
TI  - Impact of Chemical and Biological Fungicides Applied to Grapevine on Grape
      Biofilm, Must, and Wine Microbial Diversity.
AB  - This study was aimed to measure the impact of the application of a bio-fungicide
      against Botrytis cinerea on the microbiota involved in the alcoholic fermentation
      (AF) of Tempranillo Rioja wines. For this purpose, a bio-fungicide composed of
      the biological control bacterium Bacillus subtilis QST713 was applied to the
      vineyard. The microbial diversity was analyzed from grape biofilm to wine. Impact
      on microbial diversity was measured employing indexes assessed with the software
      PAST 3.10 P.D. Results were compared to non-treated samples and to samples
      treated with a chemical fungicide mainly composed by fenhexamid. Overall, the
      impact of the biological-fungicide (bio-fungicide) on the microbial diversity
      assessed for grape biofilm and for musts was not remarkable. Neither of the
      tested fungicides enhanced the growth of any species or acted against the
      development of any microbial groups. The bio-fungicide had no significant impact
      on the wine microbiota whereas the chemical fungicide caused a reduction of
      microbial community richness and diversity. Although environmental threats might
      generate a detriment of the microbial species richness, in this study the tested
      bio-fungicide did not modify the structure of the microbial community. Indeed,
      some of the Bacillus applied at the grape surface, were detected at the end of
      the AF showing its resilience to the harsh environment of the winemaking; in
      contrast, its impact on wine quality during aging is yet unknown.

PMID- 29467722
TI  - High Incidence of Pathogenic Streptococcus agalactiae ST485 Strain in
      Pregnant/Puerperal Women and Isolation of Hyper-Virulent Human CC67 Strain.
AB  - Group B streptococcus (GBS) is the major pathogen causing diseases in neonates,
      pregnant/puerperal women, cows and fish. Recent studies have shown that GBS may
      be infectious across hosts and some fish GBS strain might originate from human.
      The purpose of this study is to investigate the genetic relationship of CC103
      strains that recently emerged in cows and humans, and explore the pathogenicity
      of clinical GBS isolates from human to tilapia. Ninety-two pathogenic GBS
      isolates were identified from 19 patients with different diseases and their
      evolution and pathogenicity to tilapia were analyzed. The multilocus sequence
      typing revealed that clonal complex (CC) 103 strain was isolated from 21.74%
      (20/92) of patients and ST485 strain was from 14.13% (13/92) patients with
      multiple diseases including neonates. Genomic evolution analysis showed that both
      bovine and human CC103 strains alternately form independent evolutionary
      branches. Three CC67 isolates carried gbs2018-C gene and formed one evolutionary
      branch with ST61 and ST67 strains that specifically infect dairy cows. Studies of
      interspecies transmission to tilapia found that 21/92 (22.83%) isolates including
      all ST23 isolates were highly pathogenic to tilapia and demonstrated that
      streptococci could break through the blood-brain barrier into brain tissue. In
      conclusions, CC103 strains are highly prevalent among pathogenic GBS from humans
      and have evolved into the highly pathogenic ST485 strains specifically infecting
      humans. The CC67 strains isolated from cows are able to infect humans through
      evolutionary events of acquiring CC17-specific type C gbs2018 gene and others.
      Human-derived ST23 pathogenic GBS strains are highly pathogenic to tilapia.

PMID- 29467724
TI  - Anodic and Cathodic Extracellular Electron Transfer by the Filamentous Bacterium
      Ardenticatena maritima 110S.
AB  - Ardenticatena maritima strain 110S is a filamentous bacterium isolated from an
      iron-rich coastal hydrothermal field, and it is a unique isolate capable of
      dissimilatory iron or nitrate reduction among the members of the bacterial phylum
      Chloroflexi. Here, we report the ability of A. maritima strain 110S to utilize
      electrodes as a sole electron acceptor and donor when coupled with the oxidation
      of organic compounds and nitrate reduction, respectively. In addition,
      multicellular filaments with hundreds of cells arranged end-to-end increased the
      extracellular electron transfer (EET) ability to electrodes by organizing
      filaments into bundled structures, with the aid of microbially reduced iron oxide
      minerals on the cell surface of strain 110S. Based on these findings, together
      with the attempt to detect surface-localized cytochromes in the genome sequence
      and the demonstration of redox-dependent staining and immunostaining of the cell
      surface, we propose a model of bidirectional electron transport by A. maritima
      strain 110S, in which surface-localized multiheme cytochromes and surface
      associated iron minerals serve as a conduit of bidirectional EET in multicellular
      filaments.

PMID- 29467725
TI  - Quantitative Viral Community DNA Analysis Reveals the Dominance of Single
      Stranded DNA Viruses in Offshore Upper Bathyal Sediment from Tohoku, Japan.
AB  - Previous studies on marine environmental virology have primarily focused on
      double-stranded DNA (dsDNA) viruses; however, it has recently been suggested that
      single-stranded DNA (ssDNA) viruses are more abundant in marine ecosystems. In
      this study, we performed a quantitative viral community DNA analysis to estimate
      the relative abundance and composition of both ssDNA and dsDNA viruses in
      offshore upper bathyal sediment from Tohoku, Japan (water depth = 500 m). The
      estimated dsDNA viral abundance ranged from 3 * 106 to 5 * 106 genome copies per
      cm3 sediment, showing values similar to the range of fluorescence-based direct
      virus counts. In contrast, the estimated ssDNA viral abundance ranged from 1 *
      108 to 3 * 109 genome copies per cm3 sediment, thus providing an estimation that
      the ssDNA viral populations represent 96.3-99.8% of the benthic total DNA viral
      assemblages. In the ssDNA viral metagenome, most of the identified viral
      sequences were associated with ssDNA viral families such as Circoviridae and
      Microviridae. The principle components analysis of the ssDNA viral sequence
      components from the sedimentary ssDNA viral metagenomic libraries found that the
      different depth viral communities at the study site all exhibited similar
      profiles compared with deep-sea sediment ones at other reference sites. Our
      results suggested that deep-sea benthic ssDNA viruses have been significantly
      underestimated by conventional direct virus counts and that their contributions
      to deep-sea benthic microbial mortality and geochemical cycles should be further
      addressed by such a new quantitative approach.

PMID- 29467727
TI  - Phase Variable Expression of a Single Phage Receptor in Campylobacter jejuni
      NCTC12662 Influences Sensitivity Toward Several Diverse CPS-Dependent Phages.
AB  - Campylobacter jejuni NCTC12662 is sensitive to infection by many Campylobacter
      bacteriophages. Here we used this strain to investigate the molecular mechanism
      behind phage resistance development when exposed to a single phage and
      demonstrate how phase variable expression of one surface component influences
      phage sensitivity against many diverse C. jejuni phages. When C. jejuni NCTC12662
      was exposed to phage F207 overnight, 25% of the bacterial cells were able to grow
      on a lawn of phage F207, suggesting that resistance develops at a high frequency.
      One resistant variant, 12662R, was further characterized and shown to be an
      adsorption mutant. Plaque assays using our large phage collection showed that
      seven out of 36 diverse capsular polysaccharide (CPS)-dependent phages could not
      infect 12662R, whereas the remaining phages formed plaques on 12662R with reduced
      efficiencies. Analysis of the CPS composition of 12662R by high-resolution magic
      angle spinning nuclear magnetic resonance (HR-MAS NMR) showed a diminished signal
      for O-methyl phosphoramidate (MeOPN), a phase variable modification of the CPS.
      This suggested that the majority of the 12662R population did not express this
      phase variable modification in the CPS, indicating that MeOPN serves as a phage
      receptor in NCTC12662. Whole genome analysis of 12662R showed a switch in the
      length of the phase variable homopolymeric G tract of gene 06810, encoding a
      putative MeOPN-transferase located in the CPS locus, resulting in a non
      functional protein. To confirm the role of 06810 in phage resistance development
      of NCTC12662, a 06810 knockout mutant in NCTC12662 was constructed and analyzed
      by HR-MAS NMR demonstrating the absence of MeOPN in the CPS of the mutant. Plaque
      assays using NCTC12662Delta06810 demonstrated that seven of our CPS-dependent
      Campylobacter phages are dependent on the presence of MeOPN for successful
      infection of C. jejuni, whereas the remaining 29 phages infect independently of
      MeOPN, although with reduced efficiencies. Our data indicate that CPS-dependent
      phages uses diverse mechanisms for their initial interaction with their C. jejuni
      host.

PMID- 29467728
TI  - Urbanization Reduces Transfer of Diverse Environmental Microbiota Indoors.
AB  - Expanding urbanization is a major factor behind rapidly declining biodiversity.
      It has been proposed that in urbanized societies, the rarity of contact with
      diverse environmental microbiota negatively impacts immune function and
      ultimately increases the risk for allergies and other immune-mediated disorders.
      Surprisingly, the basic assumption that urbanization reduces exposure to
      environmental microbiota and its transfer indoors has rarely been examined. We
      investigated if the land use type around Finnish homes affects the diversity,
      richness, and abundance of bacterial communities indoors. Debris deposited on
      standardized doormats was collected in 30 rural and 26 urban households in and
      near the city of Lahti, Finland, in August 2015. Debris was weighed, bacterial
      community composition determined by high throughput sequencing of bacterial 16S
      ribosomal RNA (rRNA) gene on the Illumina MiSeq platform, and the percentage of
      four different land use types (i.e., built area, forest, transitional, and open
      area) within 200 m and 2000 m radiuses from each household was characterized. The
      quantity of doormat debris was inversely correlated with coverage of built area.
      The diversity of total bacterial, Proteobacterial, Actinobacterial,
      Bacteroidetes, and Firmicutes communities decreased as the percentage of built
      area increased. Their richness followed the same pattern except for Firmicutes
      for which no association was observed. The relative abundance of Proteobacteria
      and particularly Gammaproteobacteria increased, whereas that of Actinobacteria
      decreased with increasing built area. Neither Phylum Firmicutes nor Bacteroidetes
      varied with coverage of built area. Additionally, the relative abundance of
      potentially pathogenic bacterial families and genera increased as the percentage
      of built area increased. Interestingly, having domestic animals (including pets)
      only altered the association between the richness of Gammaproteobacteria and
      diversity of Firmicutes with the built area coverage suggesting that animal
      ownership minimally affects transfer of environmental microbiota indoors from the
      living environment. These results support the hypothesis that people living in
      densely built areas are less exposed to diverse environmental microbiota than
      people living in more sparsely built areas.

PMID- 29467726
TI  - Mitochondrial Proteins Coded by Human Tumor Viruses.
AB  - Viruses must exploit the cellular biosynthetic machinery and evade cellular
      defense systems to complete their life cycles. Due to their crucial roles in
      cellular bioenergetics, apoptosis, innate immunity and redox balance,
      mitochondria are important functional targets of many viruses, including tumor
      viruses. The present review describes the interactions between mitochondria and
      proteins coded by the human tumor viruses human T-cell leukemia virus type 1,
      Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus, human hepatitis
      viruses B and C, and human papillomavirus, and highlights how these interactions
      contribute to viral replication, persistence and transformation.

PMID- 29467729
TI  - Polymorphism in Mitochondrial Group I Introns among Cryptococcus neoformans and
      Cryptococcus gattii Genotypes and Its Association with Drug Susceptibility.
AB  - Cryptococcosis, one of the most important systemic mycosis in the world, is
      caused by different genotypes of Cryptococcus neoformans and Cryptococcus gattii,
      which differ in their ecology, epidemiology, and antifungal susceptibility.
      Therefore, the search for new molecular markers for genotyping, pathogenicity and
      drug susceptibility is necessary. Group I introns fulfill the requisites for such
      task because (i) they are polymorphic sequences; (ii) their self-splicing is
      inhibited by some drugs; and (iii) their correct splicing under parasitic
      conditions is indispensable for pathogen survival. Here, we investigated the
      presence of group I introns in the mitochondrial LSU rRNA gene in 77 Cryptococcus
      isolates and its possible relation to drug susceptibility. Sequencing revealed
      two new introns in the LSU rRNA gene. All the introns showed high sequence
      similarity to other mitochondrial introns from distinct fungi, supporting the
      hypothesis of an ancient non-allelic invasion. Intron presence was statistically
      associated with those genotypes reported to be less pathogenic (p < 0.001).
      Further virulence assays are needed to confirm this finding. In addition, in
      vitro antifungal tests indicated that the presence of LSU rRNA introns may
      influence the minimum inhibitory concentration (MIC) of amphotericin B and 5
      fluorocytosine. These findings point to group I introns in the mitochondrial
      genome of Cryptococcus as potential molecular markers for antifungal resistance,
      as well as therapeutic targets.

PMID- 29467730
TI  - Detection of Shigella in Milk and Clinical Samples by Magnetic Immunocaptured
      Loop-Mediated Isothermal Amplification Assay.
AB  - Shigella is an important human food-borne zoonosis bacterial pathogen, and can
      cause clinically severe diarrhea. There is an urgent need to develop a specific,
      sensitive, and rapid methodology for detection of this pathogen. In this study,
      loop-mediated isothermal amplification (LAMP) combined with magnetic
      immunocapture assay (IC-LAMP) was first developed for the detection of Shigella
      in pure culture, artificial milk, and clinical stool samples. This method
      exhibited a detection limit of 8.7 CFU/mL. Compared with polymerase chain
      reaction, IC-LAMP is sensitive, specific, and reliable for monitoring Shigella.
      Additionally, IC-LAMP is more convenient, efficient, and rapid than ordinary
      LAMP, as it is more efficiently enriches pathogen cells without extraction of
      genomic DNA. Under isothermal conditions, the amplification curves and the green
      fluorescence were detected within 30 min in the presence of genomic DNA template.
      The overall analysis time was approximately 1 h, including the enrichment and
      lysis of the bacterial cells, a significantly short detection time. Therefore,
      the IC-LAMP methodology described here is potentially useful for the efficient
      detection of Shigella in various samples.

PMID- 29467731
TI  - Functional Analysis of the FZF1 Genes of Saccharomyces uvarum.
AB  - Being a sister species of Saccharomyces cerevisiae, Saccharomyces uvarum shows
      great potential regarding the future of the wine industry. The sulfite tolerance
      of most S. uvarum strains is poor, however. This is a major flaw that limits its
      utility in the wine industry. In S. cerevisiae, FZF1 plays a positive role in the
      transcription of SSU1, which encodes a sulfite efflux transport protein that is
      critical for sulfite tolerance. Although FZF1 has previously been shown to play a
      role in sulfite tolerance in S. uvarum, there is little information about its
      action mechanism. To assess the function of FZF1, two over-expression vectors
      that contained different FZF1 genes, and one FZF1 silencing vector, were
      constructed and introduced into a sulfite-tolerant S. uvarum strain using
      electroporation. In addition, an FZF1-deletion strain was constructed. Both of
      the FZF1-over-expressing strains showed an elevated tolerance to sulfite, and the
      FZF1-deletion strain showed the opposite effect. Repression of FZF1 transcription
      failed, however, presumably due to the lack of alleles of DCR1 and AGO. The qRT
      PCR analysis was used to examine changes in transcription in the strains.
      Surprisingly, neither over-expressing strain promoted SSU1 transcription,
      although MET4 and HAL4 transcripts significantly increased in both sulfite
      tolerance increased strains. We conclude that FZF1 plays a different role in the
      sulfite tolerance of S. uvarum compared to its role in S. cerevisiae.

PMID- 29467732
TI  - iTRAQ-Based Comparative Proteomic Analysis of Adult Schistosoma japonicum from
      Water Buffalo and Yellow Cattle.
AB  - Schistosomiasis japonicum is one of the most severe zoonotic diseases in China.
      Water buffalo and yellow cattle are important reservoir hosts and the main
      transmission sources of Schistosoma japonicum in endemic areas. The
      susceptibility of these two hosts to schistosome infection is different, as water
      buffaloes are less susceptible to S. japonicum than yellow cattle. In this study,
      iTRAQ-coupled LC-MS/MS was applied to compare the protein expression profiles of
      adult schistosomes recovered from water buffalo with those of yellow cattle. A
      total of 131 differentially expressed proteins (DEPs) were identified, including
      46 upregulated proteins and 85 downregulated proteins. The iTRAQ results were
      confirmed by Western blotting and quantitative real-time PCR. Further analysis
      indicated that these DEPs were primarily involved in protein synthesis,
      transcriptional regulation, protein proteolysis, cytoskeletal structure and
      oxidative stress response processes. The results revealed that some of the
      differential expression molecules may affect the development and survival of
      schistosomes in these two natural hosts. Of note, this study provides useful
      information for understanding the interplay between schistosomes and their final
      hosts.

PMID- 29467733
TI  - Diversity of Rare and Abundant Prokaryotic Phylotypes in the Prony Hydrothermal
      Field and Comparison with Other Serpentinite-Hosted Ecosystems.
AB  - The Bay of Prony, South of New Caledonia, represents a unique serpentinite-hosted
      hydrothermal field due to its coastal situation. It harbors both submarine and
      intertidal active sites, discharging hydrogen- and methane-rich alkaline fluids
      of low salinity and mild temperature through porous carbonate edifices. In this
      study, we have extensively investigated the bacterial and archaeal communities
      inhabiting the hydrothermal chimneys from one intertidal and three submarine
      sites by 16S rRNA gene amplicon sequencing. We show that the bacterial community
      of the intertidal site is clearly distinct from that of the submarine sites with
      species distribution patterns driven by only a few abundant populations,
      affiliated to the Chloroflexi and Proteobacteria phyla. In contrast, the
      distribution of archaeal taxa seems less site-dependent, as exemplified by the co
      occurrence, in both submarine and intertidal sites, of two dominant phylotypes of
      Methanosarcinales previously thought to be restricted to serpentinizing systems,
      either marine (Lost City Hydrothermal Field) or terrestrial (The Cedars
      ultrabasic springs). Over 70% of the phylotypes were rare and included, among
      others, all those affiliated to candidate divisions. We finally compared the
      distribution of bacterial and archaeal phylotypes of Prony Hydrothermal Field
      with those of five previously studied serpentinizing systems of geographically
      distant sites. Although sensu stricto no core microbial community was identified,
      a few uncultivated lineages, notably within the archaeal order Methanosarcinales
      and the bacterial class Dehalococcoidia (the candidate division MSBL5) were
      exclusively found in a few serpentinizing systems while other operational
      taxonomic units belonging to the orders Clostridiales, Thermoanaerobacterales, or
      the genus Hydrogenophaga, were abundantly distributed in several sites. These
      lineages may represent taxonomic signatures of serpentinizing ecosystems. These
      findings extend our current knowledge of the microbial diversity inhabiting
      serpentinizing systems and their biogeography.

PMID- 29467734
TI  - Closing the Loop on Phosphorus Loss from Intensive Agricultural Soil: A Microbial
      Immobilization Solution?

PMID- 29467735
TI  - Genome-Based Characterization of Biological Processes That Differentiate Closely
      Related Bacteria.
AB  - Bacteriologists have strived toward attaining a natural classification system
      based on evolutionary relationships for nearly 100 years. In the early twentieth
      century it was accepted that a phylogeny-based system would be the most
      appropriate, but in the absence of molecular data, this approach proved
      exceedingly difficult. Subsequent technical advances and the increasing
      availability of genome sequencing have allowed for the generation of robust
      phylogenies at all taxonomic levels. In this study, we explored the possibility
      of linking biological characters to higher-level taxonomic groups in bacteria by
      making use of whole genome sequence information. For this purpose, we
      specifically targeted the genus Pantoea and its four main lineages. The shared
      gene sets were determined for Pantoea, the four lineages within the genus, as
      well as its sister-genus Tatumella. This was followed by functional
      characterization of the gene sets using the Kyoto Encyclopedia of Genes and
      Genomes (KEGG) database. In comparison to Tatumella, various traits involved in
      nutrient cycling were identified within Pantoea, providing evidence for increased
      efficacy in recycling of metabolites within the genus. Additionally, a number of
      traits associated with pathogenicity were identified within species often
      associated with opportunistic infections, with some support for adaptation toward
      overcoming host defenses. Some traits were also only conserved within specific
      lineages, potentially acquired in an ancestor to the lineage and subsequently
      maintained. It was also observed that the species isolated from the most diverse
      sources were generally the most versatile in their carbon metabolism. By
      investigating evolution, based on the more variable genomic regions, it may be
      possible to detect biologically relevant differences associated with the course
      of evolution and speciation.

PMID- 29467736
TI  - The Listeria monocytogenes Bile Stimulon under Acidic Conditions Is Characterized
      by Strain-Specific Patterns and the Upregulation of Motility, Cell Wall
      Modification Functions, and the PrfA Regulon.
AB  - Listeria monocytogenes uses a variety of transcriptional regulation strategies to
      adapt to the extra-host environment, the gastrointestinal tract, and the
      intracellular host environment. While the alternative sigma factor SigB has been
      proposed to be a key transcriptional regulator that facilitates L. monocytogenes
      adaptation to the gastrointestinal environment, the L. monocytogenes'
      transcriptional response to bile exposure is not well-understood. RNA-seq
      characterization of the bile stimulon was performed in two L. monocytogenes
      strains representing lineages I and II. Exposure to bile at pH 5.5 elicited a
      large transcriptomic response with ~16 and 23% of genes showing differential
      transcription in 10403S and H7858, respectively. The bile stimulon includes genes
      involved in motility and cell wall modification mechanisms, as well as genes in
      the PrfA regulon, which likely facilitate survival during the gastrointestinal
      stages of infection that follow bile exposure. The fact that bile exposure
      induced the PrfA regulon, but did not induce further upregulation of the SigB
      regulon (beyond that expected by exposure to pH 5.5), suggests a model where at
      the earlier stages of gastrointestinal infection (e.g., acid exposure in the
      stomach), SigB-dependent gene expression plays an important role. Subsequent
      exposure to bile induces the PrfA regulon, potentially priming L. monocytogenes
      for subsequent intracellular infection stages. Some members of the bile stimulon
      showed lineage- or strain-specific distribution when 27 Listeria genomes were
      analyzed. Even though sigB null mutants showed increased sensitivity to bile, the
      SigB regulon was not found to be upregulated in response to bile beyond levels
      expected by exposure to pH 5.5. Comparison of wildtype and corresponding
      DeltasigB strains newly identified 26 SigB-dependent genes, all with upstream
      putative SigB-dependent promoters.

PMID- 29467738
TI  - Worlds Apart - Transcriptome Profiles of Key Oral Microbes in the Periodontal
      Pocket Compared to Single Laboratory Culture Reflect Synergistic Interactions.
AB  - Periodontitis is a worldwide prevalent oral disease which results from dysbiosis
      of the periodontal microbiome. Some of the most active microbial players, e.g.,
      Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum, have
      extensively been studied in the laboratory, but it is unclear to which extend
      these findings can be transferred to in vivo conditions. Here we show that the
      transcriptional profiles of P. gingivalis, T. denticola, and F. nucleatum in the
      periodontal niche are distinct from those in single laboratory culture and
      exhibit functional similarities. GO (gene ontology) term enrichment analysis
      showed up-regulation of transporters, pathogenicity related traits and hemin/heme
      uptake mechanisms for all three species in vivo. Differential gene expression
      analysis revealed that cysteine proteases, transporters and hemin/heme-binding
      proteins were highly up-regulated in the periodontal niche, while genes involved
      in DNA modification were down-regulated. The data suggest strong interactions
      between those three species regarding protein degradation, iron up-take, and
      mobility in vivo, explaining their enhanced synergistic pathogenicity. We
      discovered a strikingly high frequency of Single Nucleotide Polymorphisms (SNPs)
      in vivo. For F. nucleatum we discovered a total of 127,729 SNPs in periodontal
      niche transcripts, which were found in similar frequency in health and disease
      and covered the entire genome, suggesting continuous evolution in the host. We
      conclude that metabolic interactions shape gene expression in vivo. Great caution
      is required when inferring pathogenicity of microbes from laboratory data, and
      microdiversity is an important adaptive trait of natural communities.

PMID- 29467737
TI  - Universal Vaccines and Vaccine Platforms to Protect against Influenza Viruses in
      Humans and Agriculture.
AB  - Influenza virus infections pose a significant threat to public health due to
      annual seasonal epidemics and occasional pandemics. Influenza is also associated
      with significant economic losses in animal production. The most effective way to
      prevent influenza infections is through vaccination. Current vaccine programs
      rely heavily on the vaccine's ability to stimulate neutralizing antibody
      responses to the hemagglutinin (HA) protein. One of the biggest challenges to an
      effective vaccination program lies on the fact that influenza viruses are ever
      changing, leading to antigenic drift that results in escape from earlier immune
      responses. Efforts toward overcoming these challenges aim at improving the
      strength and/or breadth of the immune response. Novel vaccine technologies, the
      so-called universal vaccines, focus on stimulating better cross-protection
      against many or all influenza strains. However, vaccine platforms or
      manufacturing technologies being tested to improve vaccine efficacy are
      heterogeneous between different species and/or either tailored for epidemic or
      pandemic influenza. Here, we discuss current vaccines to protect humans and
      animals against influenza, highlighting challenges faced to effective and uniform
      novel vaccination strategies and approaches.

PMID- 29467739
TI  - Epitope Mapping of Streptococcus agalactiae Elongation Factor Tu Protein
      Recognized by Human Sera.
AB  - The elongation factor Tu has been identified as one of the most immunoreactive
      proteins that was recognized by human sera of GBS (group B streptococcus)
      positive patients. In this paper, we present the polypeptide-specific epitopes of
      the bacterial protein that are recognized by human antibodies: 28LTAAITTVLARRLP41
      (peptide no. 3) and 294GQVLAKPGSINPHTKF309 (peptide no. 21). To determine the
      shortest amino acid sequence recognized by antibodies, truncation peptide
      libraries were prepared using the PEPSCAN method. The analysis of
      immunoreactivity of peptides with sera of GBS positive and negative women
      revealed that the most immunoreactive sequence was 306HTKF309. Moreover, we
      observed that this sequence also showed the highest specificity which was based
      on ratio of reactivity with sera of GBS positive relative to sera of GBS negative
      patients. Epitope was synthetized on Wang resin with the Fmoc strategy. Our
      results open the possibility to use 306HTKF309 peptide in diagnostic assays to
      determine Streptococcus agalactiae infection in humans.

PMID- 29467740
TI  - Genome-Wide Identification and Classification of Soybean C2H2 Zinc Finger
      Proteins and Their Expression Analysis in Legume-Rhizobium Symbiosis.
AB  - Root nodule symbiosis (RNS) is one of the most productive and economical systems
      for nitrogen fixation, and previous studies have shown that several nodule
      specific C2H2-zinc finger proteins (ZFPs) play important roles in symbiosis
      establishment and nodule function. However, C2H2-ZFPs are the most widespread
      ZFPs in eukaryotes, and a great variation of structure and function exist among
      the family members. It remains largely unclear whether or not special types of
      C2H2-ZF genes participate in symbiosis, especially in soybean. In the present
      study, we performed a genome-wide survey of soybean C2H2-ZF genes, and 321
      soybean C2H2-ZF genes were identified and classified into 11 clearly
      distinguishable subsets (Gm-t1-SF, Gm-t2-SF, Gm-1i-Q-SF, Gm-1i-M-SF, Gm-1i-Z-SF,
      Gm-1i-D-SF, Gm-2i-Q-SF, Gm-2i-M-SF, Gm-2i-Mix-SF, Gm-3i-SF, and Gm-4i-SF) based
      on the arrangements, numbers, and types of C2H2-ZF domains. Phylogenetic and gene
      ontology analyses were carried out to assess the conserved sequence and GO
      function among these subsets, and the results showed that the classification of
      soybean C2H2-ZFPs was reasonable. The expression profile of soybean C2H2-ZFPs in
      multiple tissues showed that nearly half of soybean C2H2-ZFPs within different
      subsets had expressions in nodules, including a clustering branch consisting of
      11 Gm-1i-Q-SF genes specifically expressed in symbiotic-relative tissues. RNA-Seq
      was used to identify symbiosis-related soybean C2H2-ZFPs, and the expression
      pattern of the soybean C2H2-ZFPs in roots and nodules at different development
      stages showed that soybean C2H2-ZFPs mainly played roles in nodule development or
      nodule function rather than nodulation signal transduction, and nearly half of
      these genes had high expressions and/or different expression patterns during
      soybean nodule development, especially for the six clustering branches of genes
      consisting of different subsets of C2H2-ZFPs. Furthermore, the selected symbiosis
      related soybean C2H2-ZFPs might function in legume-rhizobium symbiosis through
      regulating or interacting with other key proteins. Taken together, our findings
      provided useful information for the study on classification and conservative
      function of C2H2-ZFPs, and offered solid evidence for investigation of rhizobium
      symbiosis-related C2H2-ZFPs in soybean or other legumes.

PMID- 29467741
TI  - Interspecific Plant Interactions Reflected in Soil Bacterial Community Structure
      and Nitrogen Cycling in Primary Succession.
AB  - Past research demonstrating the importance plant-microbe interactions as drivers
      of ecosystem succession has focused on how plants condition soil microbial
      communities, impacting subsequent plant performance and plant community assembly.
      These studies, however, largely treat microbial communities as a black box. In
      this study, we sought to examine how emblematic shifts from early successional
      Alnus viridus ssp. sinuata (Sitka alder) to late successional Picea sitchensis
      (Sitka spruce) in primary succession may be reflected in specific belowground
      changes in bacterial community structure and nitrogen cycling related to the
      interaction of these two plants. We examined early successional alder-conditioned
      soils in a glacial forefield to delineate how alders alter the soil microbial
      community with increasing dominance. Further, we assessed the impact of late
      successional spruce plants on these early successional alder-conditioned
      microbiomes and related nitrogen cycling through a leachate addition microcosm
      experiment. We show how increasingly abundant alder select for particular
      bacterial taxa. Additionally, we found that spruce leachate significantly alters
      the composition of these microbial communities in large part by driving declines
      in taxa that are enriched by alder, including bacterial symbionts. We found these
      effects to be spruce specific, beyond a general leachate effect. Our work also
      demonstrates a unique influence of spruce on ammonium availability. Such insights
      bolster theory relating the importance of plant-microbe interactions with late
      successional plants and interspecific plant interactions more generally.

PMID- 29467742
TI  - Genetic Diversity and Phylogenetic Relationships of Coevolving Symbiont-Harboring
      Insect Trypanosomatids, and Their Neotropical Dispersal by Invader African
      Blowflies (Calliphoridae).
AB  - This study is about the inter- and intra-specific genetic diversity of
      trypanosomatids of the genus Angomonas, and their association with Calliphoridae
      (blowflies) in Neotropical and Afrotropical regions. Microscopic examination of
      3,900 flies of various families, mostly Calliphoridae, revealed that 31% of them
      harbored trypanosomatids. Small subunit rRNA (SSU rRNA) barcoding showed that
      Angomonas predominated (46%) over the other common trypanosomatids of blowflies
      of genera Herpetomonas and Wallacemonas. Among Angomonas spp., A. deanei was much
      more common than the two-other species, A. desouzai and A. ambiguus. Phylogenetic
      analyses based on SSU rRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase
      (gGAPDH) and internal transcribed spacer rDNA (ITS rDNA) sequences revealed a
      marked genetic diversity within A. deanei, which comprised four infraspecific
      genotypes (Dea1-Dea4), and four corresponding symbiont genotypes (Kcr1-Kcr4).
      Host and symbiont phylogenies were highly congruent corroborating their co
      divergence, consistent with host-symbiont interdependent metabolism and symbiont
      reduced genomes shaped by a long coevolutionary history. We compared the
      diversity of Angomonas/symbionts from three genera of blowflies, Lucilia,
      Chrysomya and Cochliomyia. A. deanei, A. desouzai, and A. ambiguus were found in
      the three genera of blowflies in South America. In Africa, A. deanei and A.
      ambiguus were identified in Chrysomya. The absence of A. desouzai in Africa and
      its presence in Neotropical Cochliomyia and Lucilia suggests parasite spillback
      of A. desouzai into Chrysomya, which was most likely introduced four decades ago
      from Africa into the Neotropic. The absence of correlation between parasite
      diversity and geographic and genetic distances, with identical genotypes of A.
      deanei found in the Neotropic and Afrotropic, is consistent with disjunct
      distribution due to the recent human-mediated transoceanic dispersal of Angomonas
      by Chrysomya. This study provides the most comprehensive data gathered so far on
      the genetic repertoires of a genus of trypanosomatids found in flies from a wide
      geographical range.

PMID- 29467743
TI  - Genotypic and Phenotypic Diversity of Cryptococcus gattii VGII Clinical Isolates
      and Its Impact on Virulence.
AB  - The Cryptococcus gattii species complex harbors the main etiological agents of
      cryptococcosis in immunocompetent patients. C. gattii molecular type VGII
      predominates in the north and northeastern regions of Brazil, leading to high
      morbidity and mortality rates. C. gattii VGII isolates have a strong clinical
      relevance and phenotypic variations. These phenotypic variations among C. gattii
      species complex isolates suggest that some strains are more virulent than others,
      but little information is available related to the pathogenic properties of those
      strains. In this study, we analyzed some virulence determinants of C. gattii VGII
      strains (CG01, CG02, and CG03) isolated from patients in the state of Piaui,
      Brazil. The C. gattii R265 VGIIa strain, which was isolated from the Vancouver
      outbreak, differed from C. gattii CG01, CG02 and CG03 isolates (also classified
      as VGII) when analyzed the capsular dimensions, melanin production, urease
      activity, as well as the glucuronoxylomannan (GXM) secretion. Those differences
      directly reflected in their virulence potential. In addition, CG02 displayed
      higher virulence compared to R265 (VGIIa) strain in a cryptococcal murine model
      of infection. Lastly, we examined the genotypic diversity of these strains
      through Multilocus Sequence Type (MLST) and one new subtype was described for the
      CG02 isolate. This study confirms the presence and the phenotypic and genotypic
      diversity of highly virulent strains in the Northeast region of Brazil.

PMID- 29467744
TI  - Depth-Resolved Variations of Cultivable Bacteria and Their Extracellular Enzymes
      in the Water Column of the New Britain Trench.
AB  - Marine microorganisms and their extracellular enzymes (ECEs) play an important
      role in the remineralization of organic material by hydrolyzing high-molecular
      weight substrates to sizes sufficiently small to be transported through cell
      membrane, yet the diversity of the enzyme-producing bacteria and the types of
      ECEs involved in the degradation process are largely unknown. In this work, we
      investigated the diversity of cultivable bacteria and their ECEs and the
      potential activities of aminopeptidase in the water column at eight different
      depths of the New Britain Trench. There was a great diversity of cultivable
      bacteria and ECEs, and depth appears an important driver of the diversity. The
      16S rRNA sequence analysis revealed that the cultivable bacteria were affiliated
      mostly with the phyla Proteobacteria and Actinobacteria, and the predominant
      genera were Pseudoalteromonas (62.7%) and Halomonas (17.3%). Moreover, 70.7% of
      the isolates were found to produce hydrolytic zone on casein and gelatin plates,
      in which Pseudoalteromonas was the predominant group, exhibiting relatively high
      protease production. Inhibitor analysis showed that the extracellular proteases
      from the isolated bacteria were serine proteases in the surface water and
      metalloproteases in the deep water. Meanwhile, the Vmax and Km of aminopeptidase
      exhibited a maximum in the surface water and low values in the deep bathy- and
      abyssopelagic water, indicating lower rates of hydrolysis and higher substrate
      affinity in the deeper waters. These results shed new insights into the diversity
      of the cultivable bacteria and bacterial ECEs and their likely biogeochemical
      functions in the trench environment.

PMID- 29467745
TI  - Small Non-coding RNA RyhB Mediates Persistence to Multiple Antibiotics and
      Stresses in Uropathogenic Escherichia coli by Reducing Cellular Metabolism.
AB  - As dormant phenotypic variants of bacteria, persisters account for many chronic
      infections affecting human health. Despite numerous studies, the role of small
      non-coding RNA (sRNA) in bacterial persistence has not been reported. To
      investigate the role of Hfq-interacting sRNA in persistence, we constructed the
      deletion mutants of 20 Hfq-interacting sRNAs (RyhB, GcvB, MgrR, RybB, MicF, SgrS,
      RprA, DicF, SsrS, FnrS, GadY, DsrA, OmrB, ArcZ, RyeB, RydC, OmrA, MicA, MicC, and
      ChiX) to assess their persistence capacity in uropathogenic Escherichia coli
      strain UTI89 and identified a new sRNA RyhB being involved in persister
      formation. The ryhB-knockout mutant had significant defect in persistence to a
      diverse range of antibiotics (levofloxacin, cefotaxime, gentamicin) and stresses
      (hyperosmosis, acid, and heat) in both exponential phase and stationary phase. In
      addition, the effect of RyhB on persistence was synergistic with ppGpp and Fur
      protein. RNA-Seq analysis indicated that the ryhB-knockout mutant had a
      hyperactive metabolic state compared with the parent strain. Interestingly,
      increased adenosine triphosphate (ATP) levels and altered NAD+/NADH ratios were
      observed in the ryhB-knockout mutant. Our findings represent a new level of
      persistence regulation via sRNA and may provide novel therapeutic targets for
      interventions.

PMID- 29467746
TI  - Genomic Diversity and Evolution of the Fish Pathogen Flavobacterium
      psychrophilum.
AB  - Flavobacterium psychrophilum, the etiological agent of rainbow trout fry syndrome
      and bacterial cold-water disease in salmonid fish, is currently one of the main
      bacterial pathogens hampering the productivity of salmonid farming worldwide. In
      this study, the genomic diversity of the F. psychrophilum species is analyzed
      using a set of 41 genomes, including 30 newly sequenced isolates. These were
      selected on the basis of available MLST data with the two-fold objective of
      maximizing the coverage of the species diversity and of allowing a focus on the
      main clonal complex (CC-ST10) infecting farmed rainbow trout (Oncorhynchus
      mykiss) worldwide. The results reveal a bacterial species harboring a limited
      genomic diversity both in terms of nucleotide diversity, with ~0.3% nucleotide
      divergence inside CDSs in pairwise genome comparisons, and in terms of gene
      repertoire, with the core genome accounting for ~80% of the genes in each genome.
      The pan-genome seems nevertheless "open" according to the scaling exponent of a
      power-law fitted on the rate of new gene discovery when genomes are added one-by
      one. Recombination is a key component of the evolutionary process of the species
      as seen in the high level of apparent homoplasy in the core genome. Using a
      Hidden Markov Model to delineate recombination tracts in pairs of closely related
      genomes, the average recombination tract length was estimated to ~4.0 Kbp and the
      typical ratio of the contributions of recombination and mutations to nucleotide
      level differentiation (r/m) was estimated to ~13. Within CC-ST10, evolutionary
      distances computed on non-recombined regions and comparisons between 22 isolates
      sampled up to 27 years apart suggest a most recent common ancestor in the second
      half of the nineteenth century in North America with subsequent diversification
      and transmission of this clonal complex coinciding with the worldwide expansion
      of rainbow trout farming. With the goal to promote the development of tools for
      the genetic manipulation of F. psychrophilum, a particular attention was also
      paid to plasmids. Their extraction and sequencing to completion revealed plasmid
      diversity that remained hidden to classical plasmid profiling due to size
      similarities.

PMID- 29467747
TI  - Metabolic Engineering for Enhanced Medium Chain Omega Hydroxy Fatty Acid
      Production in Escherichia coli.
AB  - Medium chain hydroxy fatty acids (HFAs) at omega-1, 2, or 3 positions (omega
      1/2/3) are rare in nature but are attractive due to their potential applications
      in industry. They can be metabolically engineered in Escherichia coli, however,
      the current yield is low. In this study, metabolic engineering with P450BM3
      monooxygenase was applied to regulate both the chain length and sub-terminal
      position of HFA products in E. coli, leading to increased yield. Five acyl-acyl
      carrier protein thioesterases from plants and bacteria were first evaluated for
      regulating the chain length of fatty acids. Co-expression of the selected
      thioesterase gene CcFatB1 with a fatty acid metabolism regulator fadR and
      monooxygenase P450BM3 boosted the production of HFAs especially omega-3-OH-C14:1,
      in both the wild type and fadD deficient strain. Supplementing renewable glycerol
      to reduce the usage of glucose as a carbon source further increased the HFAs
      production to 144 mg/L, representing the highest titer of such HFAs obtained in
      E. coli under the comparable conditions. This study illustrated an improved
      metabolic strategy for medium chain omega-1/2/3 HFAs production in E. coli. In
      addition, the produced HFAs were mostly secreted into culture media, which eased
      its recovery.

PMID- 29467748
TI  - Trace Metal Requirements and Interactions in Symbiodinium kawagutii.
AB  - Photosynthetic organisms need trace metals for various biological processes and
      different groups of microalgae have distinctive obligate necessities due to their
      respective biochemical requirements and ecological niches. We have previously
      shown that the dinoflagellate Symbiodinium kawagutii requires high concentrations
      of bioavailable Fe to achieve optimum growth. Here, we further explored the trace
      metal requirements of S. kawagutii with intensive focus on the effect of
      individual metal and its interaction with other divalent metals. We found that
      low Zn availability significantly decreases growth rates and results in elevated
      intracellular Mn, Co, Ni, and Fe quotas in the dinoflagellate. The results
      highlight the complex interaction among trace metals in S. kawagutii and suggest
      either metal replacement strategy to counter low Zn availability or enhanced
      uptake of other metals by non-specific divalent metal transporters. In this work,
      we also examined the Fe requirement of S. kawagutii using continuous cultures. We
      validated that 500 pM of Fe' was sufficient to support maximum cell density
      during steady state growth period either at 26 or 28 degrees C. This study shows
      that growth of S. kawagutii was limited by metal availability in the following
      order, Fe > Zn > Mn > Cu > Ni > Co. The fundamental information obtained for the
      free-living Symbiodinium shall provide insights into how trace metal
      availability, either from ambient seawater or hosts, affects growth and
      proliferation of symbiotic dinoflagellates and the interaction between symbiont
      and their hosts.

PMID- 29467749
TI  - Peptide Epimerization Machineries Found in Microorganisms.
AB  - D-Amino acid residues have been identified in peptides from a variety of
      eukaryotes and prokaryotes. In microorganisms, UDP-N-acetylmuramic acid
      pentapeptide (UDP-MurNAc-L-Ala-D-Glu-meso-diaminopimelate-D-Ala-D-Ala), a unit of
      peptidoglycan, is a representative. During its biosynthesis, D-Ala and D-Glu are
      generally supplied by racemases from the corresponding isomers. However, we
      recently identified a unique unidirectional L-Glu epimerase catalyzing the
      epimerization of the terminal L-Glu of UDP-MurNAc-L-Ala-L-Glu. Several such
      enzymes, introducing D-amino acid resides into peptides via epimerization, have
      been reported to date. This includes a L-Ala-D/L-Glu epimerase, which is possibly
      used during peptidoglycan degradation. In bacterial primary metabolisms, to the
      best of our knowledge, these two machineries are the only examples of peptide
      epimerization. However, a variety of peptides containing D-amino acid residues
      have been isolated from microorganisms as secondary metabolites. Their
      biosynthetic mechanisms have been studied and three different peptide
      epimerization machineries have been reported. The first is non-ribosomal peptide
      synthetase (NRPS). Excellent studies with dissected modules of gramicidin
      synthetase and tyrocidine synthetase revealed the reactions of the epimerization
      domains embedded in the enzymes. The obtained information is still utilized to
      predict epimerization domains in uncharacterized NRPSs. The second includes the
      biosynthetic enzymes of lantibiotics, which are ribosome-dependently supplied
      peptide antibiotics containing polycyclic thioether amino acids (lanthionines). A
      mechanism for the formation of the D-Ala moiety in lanthionine by two enzymes,
      dehydratases catalyzing the conversion of L-Ser into dehydroalanine and enzymes
      catalyzing nucleophilic attack of the thiol of cysteine into dehydroalanine, was
      clarified. Similarly, the formation of a D-Ala residue by reduction of the
      dehydroalanine residue was also reported. The last type of machinery includes
      radical-S-adenosylmethionine (rSAM)-dependent enzymes, which catalyze a variety
      of radical-mediated chemical transformations. In the biosynthesis of
      polytheonamide, a marine sponge-derived and ribosome-dependently supplied peptide
      composed of 48 amino acids, a rSAM enzyme (PoyD) is responsible for
      unidirectional epimerizations of multiple different amino acids in the precursor
      peptide. In this review, we briefly summarize the discovery and current
      mechanistic understanding of these peptide epimerization enzymes.

PMID- 29467750
TI  - The Peroxygenase Activity of the Aspergillus flavus Caleosin, AfPXG, Modulates
      the Biosynthesis of Aflatoxins and Their Trafficking and Extracellular Secretion
      via Lipid Droplets.
AB  - Aflatoxins (AF) are highly detrimental to human and animal health. We recently
      demonstrated that the Aspergillus flavus caleosin, AfPXG, had peroxygenase
      activity and mediated fungal development and AF accumulation. We now report the
      characterization of an AfPXG-deficient line using reference strain NRRL3357. The
      resulting fungal phenotype included a severe decrease in mycelium growth, failure
      to sporulate, and reduced AF production. Increasing cellular oxidative status by
      administration of hydrogen peroxide and cumene hydroperoxide did not restore the
      AfPXG-deficient phenotype, which suggests that AfPXG-deficiency is not directly
      related to oxidative stress. To investigate possible alternative roles of AfPXG,
      a gain of function approach was used to overexpress AfPXG, with the reporter gene
      Gfp, in an AfPXG-deficient line, termed AfPXG+ . The resulting phenotype included
      elevated numbers of stable lipid droplets (LDs) plus enhanced AF production.
      Highly purified LDs from AfPXG+ cultures sequestered AF and this ability was
      positively correlated with overall LD number. Site-specific mutagenesis of AfPXG
      to delete Histidine 85 (AfPXGHis85), a residue essential for its catalytic
      activity, or deletion of the putative LD targeting domain (AfPXGD126-140), showed
      that AfPXG-peroxygenase activity was required for AF biosynthesis and that
      integration of AF into LDs was required for their export via a LD-dependent
      pathway. Ectopic expression in fungal cells of the plant LD-associated protein,
      oleosin, also resulted in both additional LD accumulation and enhanced AF
      secretion. These results suggest that both fungal LDs and their associated
      caleosin proteins are intimately involved in the biosynthesis, trafficking, and
      secretion of AF.

PMID- 29467751
TI  - Photodynamic Vaccination of BALB/c Mice for Prophylaxis of Cutaneous
      Leishmaniasis Caused by Leishmania amazonensis.
AB  - Background: Photosensitizers (PS), like porphyrins and phthalocyanines (PC) are
      excitable by light to generate cytotoxic singlet oxygen and other reactive oxygen
      species in the presence of atmospheric O2. Photodynamic inactivation of
      Leishmania by this means renders them non-viable, but preserves their effective
      use as vaccines. Leishmania can be photo-inactivated after PS-sensitization by
      loading via their endocytic uptake of PC or endogenous induction of transgenic
      mutants with delta-aminolevulinate (ALA) to accumulate cytosolic uroporphyrin I
      (URO). Here, PS-sensitization and photo-inactivation of Leishmaniaamazonensis was
      further examined in vitro and in vivo for vaccination against cutaneous
      leishmaniasis (CL). Methods and Results:Leishmania amazonensis promastigotes were
      photodynamically inactivated in vitro by PC-loading followed by exposure to red
      light (1-2 J/cm2) or ALA-induction of uroporphyrinogenic transfectants to
      accumulate cytosolic URO followed by longwave UV exposure. When applied
      individually, both strategies of photodynamic inactivation were found to
      significantly, albeit incompletely abolish the MTT reduction activities of the
      promastigotes, their uptake by mouse bone marrow-derived macrophages in vitro and
      their infectivity to mouse ear dermis in vivo. Inactivation of Leishmania to
      completion by using a combination of both strategies was thus used for the sake
      of safety as whole-cell vaccines for immunization of BALB/c mice. Different
      cutaneous sites were assessed for the efficacy of such photodynamic vaccination
      in vivo. Each site was inoculated first with in vitro doubly PS-sensitized
      promastigotes and then spot-illuminated with white light (50 J/cm2) for their
      photo-inactivation in situ. Only in ear dermis parasites were photo-inactivated
      beyond detection. Mice were thus immunized once in the ear and challenged 3 weeks
      later at the tail base with virulent L. amazonensis. Prophylaxis was noted in
      mice photodynamically vaccinated with doubly photo-inactivated parasites, as
      indicated by a significant delay in the onset of lesion development and a
      substantial decrease in the parasite loads. Conclusion: Leishmania doubly PS
      sensitized and in situ photo-inactivated as described proved to be safe and
      effective when used for one-time immunization of ear dermis, as indicated by its
      significant protection of the inherently very susceptible BALB/c mice against CL.

PMID- 29467752
TI  - Compost Addition Enhanced Hyphal Growth and Sporulation of Arbuscular Mycorrhizal
      Fungi without Affecting Their Community Composition in the Soil.
AB  - Arbuscular mycorrhizal (AM) fungi form symbiotic associations with most crop
      plant species in agricultural ecosystems, and are conspicuously influenced by
      various agricultural practices. To understand the impact of compost addition on
      AM fungi, we examined effect of four compost rates (0, 11.25, 22.5, and 45 Mg/ha)
      on the abundance and community composition of AM fungi in seedling, flowering,
      and mature stage of soybean in a 1-year compost addition experiment system in
      Northeast China. Soybean [Glycine max (L.) Merrill] was used as test plant.
      Moderate (22.5 Mg/ha) and high (45 Mg/ha) levels of compost addition
      significantly increased AM root colonization and extraradical hyphal (ERH)
      density compared with control, whereas low (11.5 Mg/ha) level of compost addition
      did not cause significant increase in AM root colonization and ERH density. AM
      fungal spore density was significantly enhanced by all the compost rates compared
      with control. The temporal variations analysis revealed that, AM root
      colonization in seedling stage was significantly lower than in flowering and
      mature stage. Although AM fungal operational taxonomic unit richness and
      community composition was unaffected by compost addition, some abundant AM fungal
      species showed significantly different response to compost addition. In mature
      stage, Rhizophagus fasciculatum showed increasing trend along with compost
      addition gradient, whereas the opposite was observed with Paraglomus sp. In
      addition, AM fungal community composition exhibited significant temporal
      variation during growing season. Further analysis indicated that the temporal
      variation in AM fungal community only occurred in control treatment, but not in
      low, moderate, and high level of compost addition treatments. Our findings
      highlighted the significant effects of compost addition on AM growth and
      sporulation, and emphasized that growth stage is a stronger determinant than 1
      year compost addition in shaping AM fungal community in black soil of Northeast
      China.

PMID- 29467753
TI  - The Plasma Kallikrein-Kininogen Pathway Is Critical in the Pathogenesis of
      Colitis in Mice.
AB  - The kallikrein-kinin system (KKS) consists of two serine proteases, prekallikrein
      (pKal) and factor XII (FXII), and a cofactor, high-molecular-weight kininogen
      (HK). Upon activation of the KKS, HK is cleaved to release bradykinin. Although
      the KKS is activated in humans and animals with inflammatory bowel disease (IBD),
      its role in the pathogenesis of IBD has not been characterized. In the present
      study, we determined the role of the KKS in the pathogenesis of IBD using mice
      that lack proteins involved in the KKS. In two colitis models, induced by dextran
      sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS), mice
      deficient in HK, pKal, or bradykinin receptors displayed attenuated phenotypes,
      including body weight loss, disease activity index, colon length shortening,
      histological scoring, and colonic production of cytokines. Infiltration of
      neutrophils and inflammatory monocytes in the colonic lamina propria was reduced
      in HK-deficient mice. Reconstitution of HK-deficient mice through intravenous
      injection of HK recovered their susceptibility to DSS-induced colitis, increased
      IL-1beta levels in the colon tissue and bradykinin concentrations in plasma. In
      contrast to the phenotypes of other mice lacking other proteins involved in the
      KKS, mice lacking FXII had comparable colonic inflammation to that observed in
      wild-type mice. The concentration of bradykinin was significantly increased in
      the plasma of wild-type mice after DSS-induced colitis. In vitro analysis
      revealed that DSS-induced pKal activation, HK cleavage, and bradykinin plasma
      release were prevented by the absence of pKal or the inhibition of Kal. Unlike
      DSS, TNBS-induced colitis did not trigger HK cleavage. Collectively, our data
      strongly suggest that Kal, acting independently of FXII, contributes to
      experimental colitis by promoting bradykinin release from HK.

PMID- 29467754
TI  - Immune Repertoire Sequencing Using Molecular Identifiers Enables Accurate
      Clonality Discovery and Clone Size Quantification.
AB  - Unique molecular identifiers (MIDs) have been demonstrated to effectively improve
      immune repertoire sequencing (IR-seq) accuracy, especially to identify somatic
      hypermutations in antibody repertoire sequencing. However, evaluating the
      sensitivity to detect rare T cells and the degree of clonal expansion in IR-seq
      has been difficult due to the lack of knowledge of T cell receptor (TCR) RNA
      molecule copy number and a generalized approach to estimate T cell clone size
      from TCR RNA molecule quantification. This limited the application of TCR
      repertoire sequencing (TCR-seq) in clinical settings, such as detecting minimal
      residual disease in lymphoid malignancies after treatment, evaluating
      effectiveness of vaccination and assessing degree of infection. Here, we describe
      using an MID Clustering-based IR-Seq (MIDCIRS) method to quantitatively study TCR
      RNA molecule copy number and clonality in T cells. First, we demonstrated the
      necessity of performing MID sub-clustering to eliminate erroneous sequences.
      Further, we showed that MIDCIRS enables a sensitive detection of a single cell in
      as many as one million naive T cells and an accurate estimation of the degree of
      T cell clonal expression. The demonstrated accuracy, sensitivity, and wide
      dynamic range of MIDCIRS TCR-seq provide foundations for future applications in
      both basic research and clinical settings.

PMID- 29467755
TI  - Leptin Mediates In Vivo Neutrophil Migration: Involvement of Tumor Necrosis
      Factor-Alpha and CXCL1.
AB  - Leptin directly activates macrophages and lymphocytes, but the role of leptin in
      neutrophil activation and migration is still controversial. Here, we investigate
      the in vivo mechanisms of neutrophil migration induced by leptin. The
      intraperitoneal injection of leptin (1 mg/kg) induces a time- and concentration
      dependent neutrophil influx. We did not observe the enhancement of lipid
      bodies/droplets in neutrophils, after leptin treatment, as we had observed
      previously in peritoneal macrophages. The participation of leukotriene B4 (LTB4)
      in neutrophil recruitment triggered by leptin was investigated using different
      strategies. Leptin-induced neutrophil recruitment occurs both in the absence of 5
      lipoxygenase activity in 5-lipoxygenase (5-LO)-/- mice and after the
      administration of either 5-LO inhibitor (Zileuton) or the LTB4 receptor
      antagonist (U-75302). Moreover, no direct induction of LTB4 by leptin could be
      observed. Neutrophil influx could not be prevented by the mammalian target of
      rapamycin (mTOR) inhibitor, rapamycin, contrasting with the leptin-induced
      signaling for lipid body formation in macrophage that is mTOR-dependent. Leptin
      administration led to tumor necrosis factor-alpha (TNFalpha) production by the
      peritoneal cells both in vivo and in vitro. In addition, neutrophil recruitment
      was inhibited in tumor necrosis factor receptor 1 (TNFR1-/-) mice, indicating a
      role for TNF in leptin-induced neutrophil recruitment to the peritoneal cavity.
      Leptin-induced neutrophil influx was PI3Kgamma-dependent, as it was absent in
      PI3Kgamma-/- mice. Accordingly, leptin induced the peritoneal cells to produce
      CXCL1, both in vivo and in vitro, and the neutrophil influx was ablated after
      using an antibody against CXCL1. Our results establish TNFalpha/TNFR1- and CXCL1
      dependent signaling as important pathways for leptin-induced neutrophil migration
      in vivo.

PMID- 29467756
TI  - The Macrophage Mannose Receptor Regulate Mannan-Induced Psoriasis, Psoriatic
      Arthritis, and Rheumatoid Arthritis-Like Disease Models.
AB  - The injection of mannan into mice can result in the development of psoriasis (Ps)
      and psoriatic arthritis (PsA), whereas co-injection with antibodies toward
      collagen type II leads to a chronic rheumatoid-like arthritis. The critical event
      in all these diseases is mannan-mediated activation of macrophages, causing more
      severe disease if the macrophages are deficient in neutrophil cytosolic factor 1
      (Ncf1), i.e., lack the capacity to make a reactive oxygen species (ROS) burst. In
      this study, we investigated the role of one of the receptors binding mannan; the
      macrophage mannose receptor (MR, CD206). MR is a C-type lectin present on myeloid
      cells and lymphatics. We found that mice deficient in MR expression had more
      severe mannan-induced Ps, PsA as well as rheumatoid-like arthritis.
      Interestingly, the MR-mediated protection was partly lost in Ncf1 mutated mice
      and was associated with an type 2 macrophage expansion. In conclusion, these
      results show that MR protects against a pathogenic inflammatory macrophage
      response induced by mannan and is associated with induction of ROS.

PMID- 29467757
TI  - Genetic Regulation of Guanylate-Binding Proteins 2b and 5 during Leishmaniasis in
      Mice.
AB  - Interferon-induced GTPases [guanylate-binding proteins (GBPs)] play an important
      role in inflammasome activation and mediate innate resistance to many
      intracellular pathogens, but little is known about their role in leishmaniasis.
      We therefore studied expression of Gbp2b/Gbp1 and Gbp5 mRNA in skin, inguinal
      lymph nodes, spleen, and liver after Leishmania major infection and in uninfected
      controls. We used two different groups of related mouse strains: BALB/c, STS, and
      CcS-5, CcS-16, and CcS-20 that carry different combinations of BALB/c and STS
      genomes, and strains O20, C57BL/10 (B10) and B10.O20, OcB-9, and OcB-43 carrying
      different combinations of O20 and B10 genomes. The strains were classified on the
      basis of size and number of infection-induced skin lesions as highly susceptible
      (BALB/c, CcS-16), susceptible (B10.O20), intermediate (CcS-20), and resistant
      (STS, O20, B10, OcB-9, OcB-43). Some uninfected strains differed in expression of
      Gbp2b/Gbp1 and Gbp5, especially of Gbp2b/Gbp1 in skin. Uninfected BALB/c and STS
      did not differ in their expression, but in CcS-5, CcS-16, and CcS-20, which all
      carry BALB/c-derived Gbp gene-cluster, expression of Gbp2b/Gbp1 exceeds that of
      both parents. These data indicate trans-regulation of Gbps. Infection resulted in
      approximately 10* upregulation of Gbp2b/Gbp1 and Gbp5 mRNAs in organs of both
      susceptible and resistant strains, which was most pronounced in skin. CcS-20
      expressed higher level of Gbp2b/Gbp1 than both parental strains in skin, whereas
      CcS-16 expressed higher level of Gbp2b/Gbp1 than both parental strains in skin
      and liver. This indicates a trans-regulation present in infected mice CcS-16 and
      CcS-20. Immunostaining of skin of five strains revealed in resistant and
      intermediate strains STS, CcS-5, O20, and CcS-20 tight co-localization of
      Gbp2b/Gbp1 protein with most L. major parasites, whereas in the highly
      susceptible strain, BALB/c most parasites did not associate with Gbp2b/Gbp1. In
      conclusion, expression of Gbp2b/Gbp1 and Gbp5 was increased even in organs of
      clinically asymptomatic resistant mice. It suggests a hidden inflammation, which
      might contribute to control of persisting parasites. This is supported by the co
      localization of Gbpb2/Gbp1 protein and L. major parasites in skin of resistant
      and intermediate but not highly susceptible mice.

PMID- 29467758
TI  - Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic
      Hepatitis C Virus Using Pretreatment Immunological Markers.
AB  - Recent introduction of all-oral direct-acting antiviral (DAA) treatment has
      revolutionized care of patients with chronic hepatitis C virus (HCV) infection.
      Regrettably, the high cost of DAA treatment is burdensome for healthcare systems
      and may be prohibitive for some patients who would otherwise benefit.
      Understanding how patient-related factors influence individual responses to DAA
      treatment may lead to more efficient prescribing. In this observational study,
      patients with chronic HCV infection were comprehensively monitored by flow
      cytometry to identify pretreatment immunological variables that predicted HCV RNA
      negativity within 4 weeks of commencing DAA treatment. Twenty-three patients
      [genotype 1a (n = 10), 1b (n = 9), and 3 (n = 4)] were treated with daclatasvir
      plus sofosbuvir (SOF) (n = 15), ledipasvir plus SOF (n = 4), or ritonavir-boosted
      paritaprevir, ombitasvir, and dasabuvir (n = 4). DAA treatment most prominently
      altered the distribution of CD8+ memory T cell subsets. Knowing only pretreatment
      frequencies of CD3+ and naive CD8+ T cells allowed correct classification of 83%
      of patients as "fast" (HCV RNA-negative by 4 weeks) or "slow" responders. In a
      prospective cohort, these parameters correctly classified 90% of patients. Slow
      responders exhibited higher frequencies of CD3+ T cells, CD8+ TEM cells, and
      CD5high CD27- CD57+ CD8+ chronically activated T cells, which is attributed to
      bystander hyperactivation of virus-non-specific CD8+ T cells. Taken together, non
      specific, systemic CD8+ T cell activation predicted a longer time to viral
      clearance. This discovery allows pretreatment identification of individuals who
      may not require a full 12-week course of DAA therapy; in turn, this could lead to
      individualized prescribing and more efficient resource allocation.

PMID- 29467759
TI  - Magnolol Alleviates Inflammatory Responses and Lipid Accumulation by AMP
      Activated Protein Kinase-Dependent Peroxisome Proliferator-Activated Receptor
      alpha Activation.
AB  - Magnolol (MG) is a kind of lignin isolated from Magnolia officinalis, which
      serves several different biological functions, such as antifungal, anticancer,
      antioxidant, and hepatoprotective functions. This study aimed to evaluate the
      protective effect of MG against oleic acid (OA)-induced hepatic steatosis and
      inflammatory damage in HepG2 cells and in a tyloxapol (Ty)-induced hyperlipidemia
      mouse model. Our findings indicated that MG can effectively inhibit OA-stimulated
      tumor necrosis factor alpha (TNF-alpha) secretion, reactive oxygen species
      generation, and triglyceride (TG) accumulation. Further study manifested that MG
      significantly suppressed OA-activated mitogen-activated protein kinase (MAPK) and
      nuclear factor-kappa B (NF-kappaB) signaling pathways and that these inflammatory
      responses can be negated by pretreatment with inhibitors of extracellular
      regulated protein kinase and c-Jun N-terminal kinase (U0126 and SP600125,
      respectively). In addition, MG dramatically upregulated peroxisome proliferator
      activated receptor alpha (PPARalpha) translocation and reduced sterol regulatory
      element-binding protein 1c (SREBP-1c) protein synthesis and excretion, both of
      which are dependent upon the phosphorylation of adenosine monophosphate (AMP)
      activated protein kinase (AMPK), acetyl-CoA carboxylase, and AKT kinase (AKT).
      However, MG suspended the activation of PPARalpha expression and was thus blocked
      by pretreatment with LY294002 and compound c (specific inhibitors of AKT and
      AMPK). Furthermore, MG clearly alleviated serum TG and total cholesterol release;
      upregulated AKT, AMPK, and PPARalpha expression; suppressed SREBP-1c generation;
      and alleviated hepatic steatosis and dyslipidemia in Ty-induced hyperlipidemia
      mice. Taken together, these results suggest that MG exerts protective effects
      against steatosis, hyperlipidemia, and the underlying mechanism, which may be
      closely associated with AKT/AMPK/PPARalpha activation and MAPK/NF-kappaB/SREBP-1c
      inhibition.

PMID- 29467761
TI  - Establishment of the Reference Intervals of Lymphocyte Function in Healthy Adults
      Based on IFN-gamma Secretion Assay upon Phorbol-12-Myristate-13-Acetate/Ionomycin
      Stimulation.
AB  - The function of lymphocytes is the key to reflect the immune status of hosts.
      Evaluation of lymphocyte function is a useful tool to monitor the effect of
      immunosuppressive treatment and predict the prognosis of immune-mediated diseases
      (e.g., cancer, autoimmune diseases, and infectious diseases). As the lymphocytes
      have various activities, such as activation, cytotoxicity, and cytokine
      secretion, it is a challenge to evaluate the function of lymphocytes in clinical
      practice and the reference intervals (RIs) of lymphocyte function are rarely
      reported. The present study showed that the secretion of IFN-gamma was well
      correlated with the activation, chemotaxis, and cytotoxicity of CD4+, CD8+ T
      cells, and NK cells, which suggests that IFN-gamma production can be used as a
      symbol of lymphocyte function. We therefore created a simple method to detect the
      function of CD4+, CD8+ T cells, and NK cells simultaneously according to IFN
      gamma secretion by using whole blood instead of peripheral blood mononuclear
      cells. We further established the RIs of lymphocyte function (CD4+ T cells: 15.31
      34.98%; CD8+ T cells: 26.11-66.59%; NK cells: 39.43-70.79%) in healthy adults.
      This method showed good reproducibility for the evaluation of lymphocyte
      function. The established RIs were suitable for use in other centers based on the
      validation data. We also validated the RIs in individuals with different immune
      status, and the results showed that kidney transplant recipients and infants (0-1
      year) had a decreased lymphocyte function, whereas T cells in systemic lupus
      erythematosus patients exhibited an opposite trend. Overall, we have successfully
      established the RIs of lymphocyte function in healthy adults in a simple way,
      which might be of important clinical value in the diagnosis, monitoring, and
      prognosis of immune-related diseases.

PMID- 29467760
TI  - MicroRNA Regulation of Host Immune Responses following Fungal Exposure.
AB  - Fungal bioaerosols are ubiquitous in the environment and human exposure can
      result in a variety of health effects ranging from systemic, subcutaneous, and
      cutaneous infections to respiratory morbidity including allergy, asthma, and
      hypersensitivity pneumonitis. Recent research has focused on the role of
      microRNAs (miRNAs) following fungal exposure and is overlooked, yet important,
      group of regulators capable of influencing fungal immune responses through a
      variety of cellular mechanisms. These small non-coding ribose nucleic acids
      function to regulate gene expression at the post-transcriptional level and have
      been shown to participate in multiple disease pathways including cancer, heart
      disease, apoptosis, as well as immune responses to microbial hazards and
      occupational allergens. Recent animal model studies have characterized miRNAs
      following the exposure to inflammatory stimuli. Studies focused on microbial
      exposure, including bacterial infections, as well as exposure to different
      allergens have shown miRNAs, such as miR-21, miR-146, miR-132, miR-155, and the
      let-7 family members, to be involved in immune and inflammatory responses.
      Interestingly, the few studies have assessed that the miRNA profiles following
      fungal exposure have identified the same critical miRNAs that have been
      characterized in other inflammatory-mediated and allergy-induced experimental
      models. Review of available in vitro, animal and human studies of exposures to
      Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans,
      Paracoccidioides brasiliensis, and Stachybotrys chartarum identified several
      miRNAs that were shared between responses to these species including miR-125 a/b
      (macrophage polarization/activation), miR-132 [toll-like receptor (TLR)2-mediated
      signaling], miR-146a (TLR mediated signaling, alternative macrophage activation),
      and miR-29a/b (natural killer cell function, C-leptin signaling, inhibition of
      Th1 immune response). Although these datasets provide preliminary insight into
      the role of miRNAs in fungal exposed models, interpretation of miRNA datasets can
      be challenging for researchers. To assist in navigating this rapidly evolving
      field, the aim of this review is to describe miRNAs in the framework of host
      recognition mechanisms and provide initial insight into the regulatory pathways
      in response to fungal exposure.

PMID- 29467762
TI  - Inositol-Requiring Enzyme 1-Mediated Downregulation of MicroRNA (miR)-146a and
      miR-155 in Primary Dermal Fibroblasts across Three TNFRSF1A Mutations Results in
      Hyperresponsiveness to Lipopolysaccharide.
AB  - Tumor necrosis factor (TNF)-receptor-associated periodic fever syndrome (TRAPS)
      is a rare monogenic autoinflammatory disorder characterized by mutations in the
      TNFRSF1A gene, causing TNF-receptor 1 (TNFR1) misfolding, increased cellular
      stress, activation of the unfolded protein response (UPR), and
      hyperresponsiveness to lipopolysaccharide (LPS). Both microRNA (miR)-146a and miR
      155 provide negative feedback for LPS-toll-like receptor 2/4 signaling and
      cytokine production, through regulation of nuclear factor kappa B (NF-kappaB). In
      this study, we hypothesized that proinflammatory cytokine signaling in TRAPS
      downregulates these two miRs, resulting in LPS-induced hyperresponsiveness in
      TRAPS dermal fibroblasts (DFs), irrespective of the underlying genetic mutation.
      Primary DF were isolated from skin biopsies of TRAPS patients and healthy
      controls (HC). TNFR1 cell surface expression was measured using
      immunofluorescence. DF were stimulated with LPS, interleukin (IL)-1beta,
      thapsigargin, or TNF, with and without inositol-requiring enzyme 1 (IRE1)
      inhibitor (4u8C), following which miR-146a and miR-155 expression was measured by
      RT-qPCR. IL-1beta, IL-6, and TNF secretion was measured by enzyme-linked
      immunosorbent assays, and baseline expression of 384 different miRs was assessed
      using microfluidics assays. TNFR1 was found to be expressed on the surface of HC
      DF but expression was deficient in all samples with TRAPS-associated mutations.
      HC DF showed significant dose-dependent increases in both miR-146a and miR-155
      expression levels in response to LPS; however, TRAPS DF failed to upregulate
      either miR-146a or miR-155 under the same conditions. This lack of miR-146a and
      miR-155 upregulation was associated with increased proinflammatory cytokine
      production in TRAPS DF in response to LPS challenge, which was abrogated by 4u8C.
      Incubation of HC DF with IL-1beta led to downregulation of miR-146a and miR-155
      expression, which was dependent on IRE1 enzyme. We observed global dysregulation
      of hundreds of other miRs at baseline in the TRAPS DF. In summary, these data
      suggest a mechanism whereby IL-1beta, produced in response to activation of the
      UPR in TRAPS DF, downregulates miR-146a and miR-155, by inducing IRE1-dependent
      cleavage of both these miRs, thereby impairing negative regulation of NF-kappaB
      and increasing proinflammatory cytokine production.

PMID- 29467763
TI  - Functional Role of Transient Receptor Potential Channels in Immune Cells and
      Epithelia.
AB  - Transient receptor potential (TRP) ion channels are widely expressed in several
      tissues throughout the mammalian organism. Originally, TRP channel physiology was
      focusing on its fundamental meaning in sensory neuronal function. Today, it is
      known that activation of several TRP ion channels in peptidergic neurons does not
      only result in neuropeptide release and consecutive neurogenic inflammation.
      Growing evidence demonstrates functional extra-neuronal TRP channel expression in
      immune and epithelial cells with important implications for mucosal immunology.
      TRP channels maintain intracellular calcium homeostasis to regulate various
      functions in the respective cells such as nociception, production and release of
      inflammatory mediators, phagocytosis, and cell migration. In this review, we
      provide an overview about TRP-mediated effects in immune and epithelial cells
      with an emphasis on mucosal immunology of the gut. Crosstalk between neurons,
      epithelial cells, and immune cells induced by activation of TRP channels
      orchestrates the immunologic response. Understanding of its molecular mechanisms
      paves the way to novel clinical approaches for the treatment of various
      inflammatory disorders including IBD.

PMID- 29467764
TI  - Propionibacterium acnes Enhances the Immunogenicity of HIVBr18 Human
      Immunodeficiency Virus-1 Vaccine.
AB  - Immunization of BALB/c mice with HIVBr18, a DNA vaccine containing 18 CD4+ T cell
      epitopes from human immunodeficiency virus (HIV), induced specific CD4+ and CD8+
      T cell responses in a broad, polyfunctional and persistent manner. With the aim
      of increasing the immunogenicity of this vaccine, the effect of Propionibacterium
      acnes as an adjuvant was evaluated. The adjuvant effects of this bacterium have
      been extensively demonstrated in both experimental and clinical settings. Herein,
      administration of two doses of HIVBr18, in the presence of P. acnes, increased
      the proliferation of HIV-1-specific CD4+ and CD8+ T lymphocytes, the
      polyfunctional profile of CD4+ T cells, the production of IFN-gamma, and the
      number of recognized vaccine-encoded peptides. One of the bacterial components
      responsible for most of the adjuvant effects observed was a soluble
      polysaccharide extracted from the P. acnes cell wall. Furthermore, within 10
      weeks after immunization, the proliferation of specific T cells and production of
      IFN-gamma were maintained when the whole bacterium was administered,
      demonstrating a greater effect on the longevity of the immune response by P.
      acnes. Even with fewer immunization doses, P. acnes was found to be a potent
      adjuvant capable of potentiating the effects of the HIVBr18 vaccine. Therefore,
      P. acnes may be a potential adjuvant to aid this vaccine in inducing immunity or
      for therapeutic use.

PMID- 29467765
TI  - Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil
      Extracellular Traps by Suppressing Neutrophil Adhesion.
AB  - Hospital-acquired infections caused by Acinetobacter baumannii have become
      problematic because of high rates of drug resistance. A. baumannii is usually
      harmless, but it may cause infectious diseases in an immunocompromised host.
      Although neutrophils are the key players of the initial immune response against
      bacterial infection, their interactions with A. baumannii remain largely unknown.
      A new biological defense mechanism, termed neutrophil extracellular traps (NETs),
      has been attracting attention. NETs play a critical role in bacterial killing by
      bacterial trapping and inactivation. Many pathogenic bacteria have been reported
      to induce NET formation, while an inhibitory effect on NET formation is rarely
      reported. In the present study, to assess the inhibition of NET formation by A.
      baumannii, bacteria and human neutrophils were cocultured in the presence of
      phorbol 12-myristate 13-acetate (PMA), and NET formation was evaluated. NETs were
      rarely observed during the coculture despite neutrophil PMA stimulation.
      Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET
      formation. The inhibition of NET formation by other bacteria was also
      investigated. The inhibitory effect was only apparent with live A. baumannii
      cells. Finally, to elucidate the mechanism of this inhibition, neutrophil
      adhesion was examined. A. baumannii suppressed the adhesion ability of
      neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of
      cell adhesion was partly due to suppression of the surface expression of CD11a in
      neutrophils. The current study constitutes the first report on the inhibition of
      NET formation by a pathogenic bacterium, A. baumannii, and prolonging the
      neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby
      escaping host immune responses might contribute to a development of new treatment
      strategies for A. baumannii infections.

PMID- 29467766
TI  - Editorial: Reassessing Twenty Years of Vaccine Development against Tuberculosis.

PMID- 29467767
TI  - Identification of Casz1 as a Regulatory Protein Controlling T Helper Cell
      Differentiation, Inflammation, and Immunity.
AB  - While T helper (Th) cells play a crucial role in host defense, an imbalance in Th
      effector subsets due to dysregulation in their differentiation and expansion
      contribute to inflammatory disorders. Here, we show that Casz1, whose function is
      previously unknown in CD4+ T cells, coordinates Th differentiation in vitro and
      in vivo. Casz1 deficiency in CD4+ T cells lowers susceptibility to experimental
      autoimmune encephalomyelitis, consistent with the reduced frequency of Th17
      cells, despite an increase in Th1 cells in mice. Loss of Casz1 in the context of
      mucosal Candida infection severely impairs Th17 and Treg responses, and lowers
      the ability of the mice to clear the secondary infection. Importantly, in both
      the models, absence of Casz1 causes a significant diminution in IFN-gamma+IL-17A+
      double-positive inflammatory Th17 cells (Th1* cells) in tissues in vivo.
      Transcriptome analyses of CD4+ T cells lacking Casz1 show a signature consistent
      with defective Th17 differentiation. With regards to Th17 differentiation, Casz1
      limits repressive histone marks and enables acquisition of permissive histone
      marks at Rorc, Il17a, Ahr, and Runx1 loci. Taken together, these data identify
      Casz1 as a new Th plasticity regulator having important clinical implications for
      autoimmune inflammation and mucosal immunity.

PMID- 29467768
TI  - Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells.
AB  - Innate lymphoid cells (ILCs) are an essential component of the innate immune
      system in vertebrates. They are developmentally rooted in the lymphoid lineage
      and can diverge into at least three transcriptionally distinct lineages. ILCs
      seed both lymphoid and non-lymphoid tissues and are locally self-maintained in
      tissue-resident pools. Tissue-resident ILCs execute important effector functions
      making them key regulator in tissue homeostasis, repair, remodeling, microbial
      defense, and anti-tumor immunity. Similar to T lymphocytes, ILCs possess only few
      sensory elements for the recognition of non-self and thus depend on extrinsic
      cellular sensory elements residing within the tissue. Myeloid cells, including
      mononuclear phagocytes (MNPs), are key sentinels of the tissue and are able to
      translate environmental cues into an effector profile that instructs lymphocyte
      responses. The adaptation of myeloid cells to the tissue state thus influences
      the effector program of ILCs and serves as an example of how environmental
      signals are integrated into the function of ILCs via a tissue-resident immune
      cell cross talks. This review summarizes our current knowledge on the role of
      myeloid cells in regulating ILC functions and discusses how feedback
      communication between ILCs and myeloid cells contribute to stabilize immune
      homeostasis in order to maintain the healthy state of an organ.

PMID- 29467770
TI  - Cytokines Stimulate the Release of Microvesicles from Myeloid Cells Independently
      from the P2X7 Receptor/Acid Sphingomyelinase Pathway.
AB  - Microvesicles (MVs) are membrane particles of 200-500 nm released by all cell
      types constitutively. MVs of myeloid origin are found increased in the
      cerebrospinal fluid (CSF) of patients suffering from neuroinflammatory disorders,
      although the factors triggering their production have never been defined. Here,
      we report that both pro- and anti-inflammatory cytokines, specifically interferon
      gamma and interleukin-4, are equally able to stimulate the production of MVs from
      microglia cells and monocytes. Additionally, we found this process to be
      independent from the best characterized molecular pathway so far described for
      membrane shedding, which is centered on the purinergic receptor P2X7, whose
      activation by high concentrations of extracellular ATP (exATP) results in
      membrane blebbing operated by the secreted enzyme acid sphingomyelinase (ASMase).
      Moreover, a potent inhibitor of ASMase, injected in a mouse model of multiple
      sclerosis, failed to reduce the number of MVs in their CSF. This suggests that
      cytokines, rather than exATP, may exert a long-term control of MV production in
      the context of chronic inflammation, where both pro- and anti-inflammatory
      factors play coordinated roles.

PMID- 29467769
TI  - CD137+CD154- Expression As a Regulatory T Cell (Treg)-Specific Activation
      Signature for Identification and Sorting of Stable Human Tregs from In Vitro
      Expansion Cultures.
AB  - Regulatory T cells (Tregs) are an attractive therapeutic tool for several
      different immune pathologies. Therapeutic Treg application often requires
      prolonged in vitro culture to generate sufficient Treg numbers or to optimize
      their functionality, e.g., via genetic engineering of their antigen receptors.
      However, purity of clinical Treg expansion cultures is highly variable, and
      currently, it is impossible to identify and separate stable Tregs from
      contaminating effector T cells, either ex vivo or after prior expansion. This
      represents a major obstacle for quality assurance of expanded Tregs and raises
      significant safety concerns. Here, we describe a Treg activation signature that
      allows identification and sorting of epigenetically imprinted Tregs even after
      prolonged in vitro culture. We show that short-term reactivation resulted in
      expression of CD137 but not CD154 on stable FoxP3+ Tregs that displayed a
      demethylated Treg-specific demethylated region, high suppressive potential, and
      lack of inflammatory cytokine expression. We also applied this Treg activation
      signature for rapid testing of chimeric antigen receptor functionality in human
      Tregs and identified major differences in the signaling requirements regarding
      CD137 versus CD28 costimulation. Taken together, CD137+CD154- expression emerges
      as a universal Treg activation signature ex vivo and upon in vitro expansion
      allowing the identification and isolation of epigenetically stable antigen
      activated Tregs and providing a means for their rapid functional testing in
      vitro.

PMID- 29467771
TI  - Association of microRNAs with Types of Leaf Curvature in Brassica rapa.
AB  - Many vegetable crops of Brassica rapa are characterized by their typical types of
      leaf curvature. Leaf curvature in the right direction and to the proper degree is
      important for the yield and quality of green vegetable products, when cultivated
      under stress conditions. Recent research has unveiled some of the roles of miRNAs
      in Brassica crops such as how they regulate the timing of leafy head initiation
      and shape of the leafy head. However, the molecular mechanism underlying the
      variability in leaf curvature in B. rapa remains unclear. We tested the
      hypothesis that the leaf curvature of B. rapa is affected by miRNA levels. On the
      basis of leaf phenotyping, 56 B. rapa accessions were classified into five leaf
      curvature types, some of which were comparable to miRNA mutants of Arabidopsis
      thaliana in phenotype. Higher levels of miR166 and miR319a expression were
      associated with downward curvature and wavy margins, respectively. Overexpression
      of the Brp-MIR166g-1 gene caused rosette leaves to change from flat to downward
      curving and folding leaves to change from upward curving to flat, leading to the
      decrease in the number of incurved leaves and size of the leafy head. Our results
      reveal that miRNAs affect the types of leaf curvature in B. rapa. These findings
      provide insight into the relationship between miRNAs and variation in leaf
      curvature.

PMID- 29467772
TI  - Genetic and Genomic Tools to Asssist Sugar Beet Improvement: The Value of the
      Crop Wild Relatives.
AB  - Sugar beet (Beta vulgaris L. ssp. vulgaris) is one of the most important European
      crops for both food and sugar production. Crop improvement has been developed to
      enhance productivity, sugar content or other breeder's desirable traits. The
      introgression of traits from Crop Wild Relatives (CWR) has been done essentially
      for lessening biotic stresses constraints, namely using Beta and Patellifolia
      species which exhibit disease resistance characteristics. Several studies have
      addressed crop-to-wild gene flow, yet, for breeding programs genetic variability
      associated with agronomically important traits remains unexplored regarding
      abiotic factors. To accomplish such association from phenotype-to-genotype,
      screening for wild relatives occurring in habitats where selective pressures are
      in play (i.e., populations in salt marshes for salinity tolerance; populations
      subjected to pathogen attacks and likely evolved resistance to pathogens) are the
      most appropriate streamline to identify causal genetic information. By selecting
      sugar beet CWR species based on genomic tools, rather than random variations, is
      a promising but still seldom explored route toward the development of improved
      crops. In this perspective, a viable streamline for sugar beet improvement is
      proposed through the use of different genomic tools by recurring to sugar beet
      CWRs and focusing on agronomic traits associated with abiotic stress tolerance.
      Overall, identification of genomic and epigenomic landscapes associated to
      adaptive ecotypes, along with the cytogenetic and habitat characterization of
      sugar beet CWR, will enable to identify potential hotspots for agrobiodiversity
      of sugar beet crop improvement toward abiotic stress tolerance.

PMID- 29467773
TI  - Characterization of Novel Plant Symbiosis Mutants Using a New Multiple Gene
      Expression Reporter Sinorhizobium meliloti Strain.
AB  - The formation of nitrogen fixing root nodules by Medicago truncatula and
      Sinorhizobium meliloti requires communication between both organisms and
      coordinated differentiation of plant and bacterial cells. After an initial signal
      exchange, the bacteria invade the tissue of the growing nodule via plant-derived
      tubular structures, called infection threads. The bacteria are released from the
      infection threads into invasion-competent plant cells, where they differentiate
      into nitrogen-fixing bacteroids. Both organisms undergo dramatic transcriptional,
      metabolic and morphological changes during nodule development. To identify plant
      processes that are essential for the formation of nitrogen fixing nodules after
      nodule development has been initiated, large scale mutageneses have been
      conducted to discover underlying plant symbiosis genes. Such screens yield
      numerous uncharacterized plant lines with nitrogen fixation deficient nodules. In
      this study, we report construction of a S. meliloti strain carrying four distinct
      reporter constructs to reveal stages of root nodule development. The strain
      contains a constitutively expressed lacZ reporter construct; a PexoY-mTFP fusion
      that is expressed in infection threads but not in differentiated bacteroids; a
      PbacA-mcherry construct that is expressed in infection threads and during
      bacteroid differentiation; and a PnifH-uidA construct that is expressed during
      nitrogen fixation. We used this strain together with fluorescence microscopy to
      study nodule development over time in wild type nodules and to characterize eight
      plant mutants from a fast neutron bombardment screen. Based on the signal
      intensity and the localization patterns of the reporter genes, we grouped mutants
      with similar phenotypes and placed them in a developmental context.

PMID- 29467774
TI  - Genome-Based Prediction of Time to Curd Induction in Cauliflower.
AB  - The development of cauliflower (Brassica oleracea var. botrytis) is highly
      dependent on temperature due to vernalization requirements, which often causes
      delay and unevenness in maturity during months with warm temperatures.
      Integrating quantitative genetic analyses with phenology modeling was suggested
      to accelerate breeding strategies toward wide-adaptation cauliflower. The present
      study aims at establishing a genome-based model simulating the development of
      doubled haploid (DH) cauliflower lines to predict time to curd induction of DH
      lines not used for model parameterization and test hybrids derived from the bi
      parental cross. Leaf appearance rate and the relation between temperature and
      thermal time to curd induction were examined in greenhouse trials on 180 DH lines
      at seven temperatures. Quantitative trait loci (QTL) analyses carried out on
      model parameters revealed ten QTL for leaf appearance rate (LAR), five for the
      slope and two for the intercept of linear temperature-response functions. Results
      of the QTL-based phenology model were compared to a genomic selection (GS) model.
      Model validation was carried out on data comprising four field trials with 72
      independent DH lines, 160 hybrids derived from the parameterization set, and 34
      hybrids derived from independent lines of the population. The QTL model resulted
      in a moderately accurate prediction of time to curd induction (R2 = 0.42-0.51)
      while the GS model generated slightly better results (R2 = 0.52-0.61).
      Predictions of time to curd induction of test hybrids from independent DH lines
      were less precise with R2 = 0.40 for the QTL and R2 = 0.48 for the GS model.
      Implementation of juvenile-to-adult phase transition is proposed for model
      improvement.

PMID- 29467775
TI  - Intra-annual Dynamics of Xylem Formation in Liquidambar formosana Subjected to
      Canopy and Understory N Addition.
AB  - Increasing N deposition caused by intensive anthropogenic activities is expected
      to affect forest growth. However, the effects of N deposition on trees are still
      controversial due to the wide variability in results and experimental methods
      used. We conducted an experiment involving both canopy and understory N addition
      to investigate the effects of N-addition on intra-annual xylem formation of
      Chinese sweetgum (Liquidambar formosana) in a warm-temperate forest of Central
      China. Since 2013, 50 kg N ha-1 year-1 (2.5 times the current natural N
      deposition) was applied monthly from April to December. In 2014 and 2015, the
      timing and dynamics of xylem formation were monitored weekly during March
      December by microcoring the stems of control and treated trees. Similar dynamics
      of wood formation were observed between canopy and understory N addition. Xylem
      formation of all the experimental trees started in March and lasted for 119-292
      days. Compared to the control, no change was observed in the timing and dynamics
      of wood formation in N-treated trees. Tree ring-width ranged between 1701 and
      4774 MUm, with a rate of xylem production of 10.52-26.64 MUm day-1. The radial
      growth of trees was not modified by the treatments. Our findings suggest that
      short-term N addition is unable to affect the dynamics of xylem formation in
      Chinese sweetgum in Central China. The effects of N on tree growth observed in
      previous studies might be related to the duration of the experiment or the
      imbalance between the amount of natural deposition and N added during treatments.

PMID- 29467777
TI  - Interannual Change Detection of Mediterranean Seagrasses Using RapidEye Image
      Time Series.
AB  - Recent research studies have highlighted the decrease in the coverage of
      Mediterranean seagrasses due to mainly anthropogenic activities. The lack of data
      on the distribution of these significant aquatic plants complicates the
      quantification of their decreasing tendency. While Mediterranean seagrasses are
      declining, satellite remote sensing technology is growing at an unprecedented
      pace, resulting in a wealth of spaceborne image time series. Here, we exploit
      recent advances in high spatial resolution sensors and machine learning to study
      Mediterranean seagrasses. We process a multispectral RapidEye time series between
      2011 and 2016 to detect interannual seagrass dynamics in 888 submerged hectares
      of the Thermaikos Gulf, NW Aegean Sea, Greece (eastern Mediterranean Sea). We
      assess the extent change of two Mediterranean seagrass species, the dominant
      Posidonia oceanica and Cymodocea nodosa, following atmospheric and analytical
      water column correction, as well as machine learning classification, using Random
      Forests, of the RapidEye time series. Prior corrections are necessary to untangle
      the initially weak signal of the submerged seagrass habitats from satellite
      imagery. The central results of this study show that P. oceanica seagrass area
      has declined by 4.1%, with a trend of -11.2 ha/yr, while C. nodosa seagrass area
      has increased by 17.7% with a trend of +18 ha/yr throughout the 5-year study
      period. Trends of change in spatial distribution of seagrasses in the Thermaikos
      Gulf site are in line with reported trends in the Mediterranean. Our presented
      methodology could be a time- and cost-effective method toward the quantitative
      ecological assessment of seagrass dynamics elsewhere in the future. From small
      meadows to whole coastlines, knowledge of aquatic plant dynamics could resolve
      decline or growth trends and accurately highlight key units for future
      restoration, management, and conservation.

PMID- 29467776
TI  - Genome-Wide Association Analyses Identify QTL Hotspots for Yield and Component
      Traits in Durum Wheat Grown under Yield Potential, Drought, and Heat Stress
      Environments.
AB  - Understanding the genetic bases of economically important traits is fundamentally
      important in enhancing genetic gains in durum wheat. In this study, a durum panel
      of 208 lines (comprised of elite materials and exotics from the International
      Maize and Wheat Improvement Center gene bank) were subjected to genome wide
      association study (GWAS) using 6,211 DArTseq single nucleotide polymorphisms
      (SNPs). The panel was phenotyped under yield potential (YP), drought stress (DT),
      and heat stress (HT) conditions for 2 years. Mean yield of the panel was reduced
      by 72% (to 1.64 t/ha) under HT and by 60% (to 2.33 t/ha) under DT, compared to YP
      (5.79 t/ha). Whereas, the mean yield of the panel under HT was 30% less than
      under DT. GWAS identified the largest number of significant marker-trait
      associations on chromosomes 2A and 2B with p-values 10-06 to 10-03 and the
      markers from the whole study explained 7-25% variation in the traits. Common
      markers were identified for stress tolerance indices: stress susceptibility
      index, stress tolerance, and stress tolerance index estimated for the traits
      under DT (82 cM on 2B) and HT (68 and 83 cM on 3B; 25 cM on 7A). GWAS of
      irrigated (YP and HT combined), stressed (DT and HT combined), combined analysis
      of three environments (YP + DT + HT), and its comparison with trait per se and
      stress indices identified QTL hotspots on chromosomes 2A (54-70 cM) and 2B (75-82
      cM). This study enhances our knowledge about the molecular markers associated
      with grain yield and its components under different stress conditions. It
      identifies several marker-trait associations for further exploration and
      validation for marker-assisted breeding.

PMID- 29467778
TI  - Effects of Inundation, Nutrient Availability and Plant Species Diversity on Fine
      Root Mass and Morphology Across a Saltmarsh Flooding Gradient.
AB  - Saltmarsh plants are exposed to multiple stresses including tidal inundation,
      salinity, wave action and sediment anoxia, which require specific root system
      adaptations to secure sufficient resource capture and firm anchorage in a
      temporary toxic environment. It is well known that many saltmarsh species develop
      large below-ground biomass (roots and rhizomes) but relations between fine roots,
      in particular, and the abiotic conditions in salt marshes are widely unknown. We
      studied fine root mass (<2 mm in diameter), fine root depth distribution and fine
      root morphology in three typical communities (Spartina anglica-dominated pioneer
      zone, Atriplex portulacoides-dominated lower marsh, Elytrigia atherica-dominated
      upper marsh) across elevational gradients in two tidal salt marshes of the German
      North Sea coast [a mostly sandy marsh on a barrier island (Spiekeroog), and a
      silty-clayey marsh on the mainland coast (Westerhever)]. Fine root mass in the 0
      40 cm profile ranged between 750 and 2,500 g m-2 in all plots with maxima at both
      sites in the lower marsh with intermediate inundation frequency and highest plant
      species richness indicating an effect of biodiversity on fine root mass. Fine
      root mass and, even more, total fine root surface area (maximum 340 m2 m-2) were
      high compared to terrestrial grasslands, and were greater in the nutrient-poorer
      Spiekeroog marsh. Fine root density showed only a slight or no decrease toward 40
      cm depth. We conclude that the standing fine root mass and morphology of these
      salt marshes is mainly under control of species identity and nutrient
      availability, but species richness is especially influential. The plants of the
      pioneer zone and lower marsh possess well adapted fine roots and large standing
      root masses despite the often water-saturated sediment.

PMID- 29467779
TI  - OsVIL2 Regulates Spikelet Development by Controlling Regulatory Genes in Oryza
      sativa.
AB  - Flower organ patterning is accomplished by spatial and temporal functioning of
      various regulatory genes. We previously reported that Oryza sativa VIN3-LIKE 2
      (OsVIL2) induces flowering by mediating the trimethylation of Histone H3 on LFL1
      chromatin. In this study, we report that OsVIL2 also plays crucial roles during
      spikelet development. Two independent lines of T-DNA insertional mutants in the
      gene displayed altered organ numbers and abnormal morphology in all spikelet
      organs. Scanning electron microscopy showed that osvil2 affected organ primordia
      formation during early spikelet development. Expression analysis revealed that
      OsVIL2 is expressed in all stages of the spikelet developmental. Transcriptome
      analysis of developing spikelets revealed that several regulatory genes involved
      in that process and the formation of floral organs were down-regulated in osvil2.
      These results suggest that OsVIL2 is required for proper expression of the
      regulatory genes that control floral organ number and morphology.

PMID- 29467780
TI  - Development and Applications of a High Throughput Genotyping Tool for Polyploid
      Crops: Single Nucleotide Polymorphism (SNP) Array.
AB  - Polypoid species play significant roles in agriculture and food production. Many
      crop species are polyploid, such as potato, wheat, strawberry, and sugarcane.
      Genotyping has been a daunting task for genetic studies of polyploid crops, which
      lags far behind the diploid crop species. Single nucleotide polymorphism (SNP)
      array is considered to be one of, high-throughput, relatively cost-efficient and
      automated genotyping approaches. However, there are significant challenges for
      SNP identification in complex, polyploid genomes, which has seriously slowed SNP
      discovery and array development in polyploid species. Ploidy is a significant
      factor impacting SNP qualities and validation rates of SNP markers in SNP arrays,
      which has been proven to be a very important tool for genetic studies and
      molecular breeding. In this review, we (1) discussed the pros and cons of SNP
      array in general for high throughput genotyping, (2) presented the challenges of
      and solutions to SNP calling in polyploid species, (3) summarized the SNP
      selection criteria and considerations of SNP array design for polyploid species,
      (4) illustrated SNP array applications in several different polyploid crop
      species, then (5) discussed challenges, available software, and their accuracy
      comparisons for genotype calling based on SNP array data in polyploids, and
      finally (6) provided a series of SNP array design and genotype calling
      recommendations. This review presents a complete overview of SNP array
      development and applications in polypoid crops, which will benefit the research
      in molecular breeding and genetics of crops with complex genomes.

PMID- 29467781
TI  - Overexpression of a Functional Vicia sativa PCS1 Homolog Increases Cadmium
      Tolerance and Phytochelatins Synthesis in Arabidopsis.
AB  - Phytochelatins (PCs) catalyzed by phytochelatin synthases (PCS) are important for
      the detoxification of metals in plants and other living organisms. In this study,
      we isolated a PCS gene (VsPCS1) from Vicia sativa and investigated its role in
      regulating cadmium (Cd) tolerance. Expression of VsPCS1 was induced in roots of
      V. sativa under Cd stress. Analysis of subcellular localization showed that
      VsPCS1 was localized in the cytoplasm of mesophyll protoplasts of V. sativa.
      Overexpression of VsPCS1 (35S::VsPCS1, in wild-type background) in Arabidopsis
      thaliana could complement the defects of Cd tolerance of AtPCS1-deficent mutant
      (atpcs1). Compared with atpcs1 mutants, 35S::VsPCS1/atpcs1 (in AtPCS1-deficent
      mutant background) transgenic plants significantly lowered Cd-fluorescence
      intensity in mesophyll cytoplasm, accompanied with enhanced Cd-fluorescence
      intensity in the vacuoles, demonstrating that the increased Cd tolerance may be
      attributed to the increased PC-based sequestration of Cd into the vacuole.
      Furthermore, overexpressing VsPCS1 could enhance the Cd tolerance in 35S::VsPCS1,
      but have no effect on Cd accumulation and distribution, showing the same level of
      Cd-fluorescence intensity between 35S::VsPCS1 and wild-type (WT) plants. Further
      analysis indicated this increased tolerance in 35S::VsPCS1 was possibly due to
      the increased PCs-chelated Cd in cytosol. Taken together, a functional PCS1
      homolog from V. sativa was identified, which hold a strong catalyzed property for
      the synthesis of high-order PCs that retained Cd in the cytosol rather the
      vacuole. These findings enrich the original model of Cd detoxification mediated
      by PCS in higher plants.

PMID- 29467782
TI  - LasDelta5315 Effector Induces Extreme Starch Accumulation and Chlorosis as Ca.
      Liberibacter asiaticus Infection in Nicotiana benthamiana.
AB  - Huanglongbing (HLB), a destructive plant bacterial disease, severely impedes
      worldwide citrus production. HLB is associated with a phloem-limited alpha
      proteobacterium, Candidatus Liberibacter asiaticus (Las). Las infection causes
      yellow shoots and blotchy mottle on leaves and is associated with excessive
      starch accumulation. However, the mechanisms underlying the starch accumulation
      remain unknown. We previously showed that the Las5315mp effector induced callose
      deposition and cell death in Nicotiana benthamiana. In this study, we
      demonstrated that Las can experimentally infect N. benthamiana via dodder
      transmission. Furthermore, we revealed another key function of the Las5315
      effector by demonstrating that transient expression of the truncated form of the
      effector, LasDelta5315, induced excessive starch accumulation by 6 fold after 8
      dpi in N. benthamiana after removal of the chloroplast transit peptide from the
      Las5315mp. The induction mechanisms of LasDelta5315 in N. benthamiana were
      attributed to the up-regulation of ADP-glucose pyrophosphorylase, granule-bound
      starch synthase, soluble starch synthase, and starch branching enzyme for
      increasing starch production, and to the significant down-regulation of the
      starch degradation enzymes: alpha-glucosidase, alpha-amylase, and glycosyl
      hydrolase for decreasing starch degradation. This is the first report that Las
      can infect the model plant N. benthamiana. Using this model plant, we
      demonstrated that the LasDelta5315 effector caused the most prominent HLB
      symptoms, starch accumulation and chlorosis as Las infection in N. benthamiana.
      Altogether the Las 5315 effector is critical for Las pathogenesis, and therefore,
      an important target for interference.

PMID- 29467783
TI  - A Genomic View of Alternative Splicing of Long Non-coding RNAs during Rice Seed
      Development Reveals Extensive Splicing and lncRNA Gene Families.
AB  - Alternative splicing (AS) is a key modulator of development in many eukaryotic
      organisms. In plants, alternative splice forms of non-coding RNAs (ncRNAs) are
      known to modulate flowering time in Arabidopsis and fertility in rice. Here we
      demonstrate that alternative splicing of coding and long non-coding RNAs occurs
      during rice seed development by comparing AS in immature seeds vs. embryo and
      endosperm of mature seeds. Based on computational predictions of AS events
      determined from a Bayesian analysis of junction counts of RNA-seq datasets,
      differential splicing of protein-coding, and non-coding RNAs was determined. In
      contrast to roots, leaves, flowers, buds, and reproductive meristems, developing
      seeds had 5.8-57 times more predicted AS. Primers designed to span introns and
      exons were used to detect AS events predicted by rMATs in cDNA derived from early
      (milk) seed, embryo, and endosperm. Comparing milk seed vs. mature embryo and
      endosperm, AS of MORC7 (a gene implicated in epigenetic gene silencing), was
      markedly different. Long non-coding RNAs (lncRNAs) also underwent AS during the
      transition from milk seed to mature embryo and endosperm, with a complex gene
      structure, and were more extensively processed than predicted by current genome
      annotation. Exon retention of lncRNAs was enhanced in embryos. Searching all
      5,515 lncRNAs in the NCBI genome annotation uncovered gene families based on
      highly conserved regions shared by groups of 3-35 lncRNAs. The homologies to
      other lncRNAs, as well as homologies to coding sequences, and the genomic context
      of lncRNAs provide inroads for functional analysis of multi-exonic lncRNAs that
      can be extensively processed during seed development.

PMID- 29467784
TI  - Heterologous Expression of the Cotton NBS-LRR Gene GbaNA1 Enhances Verticillium
      Wilt Resistance in Arabidopsis.
AB  - Verticillium wilt caused by Verticillium dahliae results in severe losses in
      cotton, and is economically the most destructive disease of this crop. Improving
      genetic resistance is the cleanest and least expensive option to manage
      Verticillium wilt. Previously, we identified the island cotton NBS-LRR-encoding
      gene GbaNA1 that confers resistance to the highly virulent V. dahliae isolate
      Vd991. In this study, we expressed cotton GbaNA1 in the heterologous system of
      Arabidopsis thaliana and investigated the defense response mediated by GbaNA1
      following inoculations with V. dahliae. Heterologous expression of GbaNA1
      conferred Verticillium wilt resistance in A. thaliana. Moreover, overexpression
      of GbaNA1 enabled recovery of the resistance phenotype of A. thaliana mutants
      that had lost the function of GbaNA1 ortholog gene. Investigations of the defense
      response in A. thaliana showed that the reactive oxygen species (ROS) production
      and the expression of genes associated with the ethylene signaling pathway were
      enhanced significantly following overexpression of GbaNA1. Intriguingly,
      overexpression of the GbaNA1 ortholog from Gossypium hirsutum (GhNA1) in A.
      thaliana did not induce the defense response of ROS production due to the
      premature termination of GhNA1, which lacks the encoded NB-ARC and LRR motifs.
      GbaNA1 therefore confers Verticillium wilt resistance in A. thaliana by the
      activation of ROS production and ethylene signaling. These results demonstrate
      the functional conservation of the NBS-LRR-encoding GbaNA1 in a heterologous
      system, and the mechanism of this resistance, both of which may prove valuable in
      incorporating GbaNA1-mediated resistance into other plant species.

PMID- 29467785
TI  - Morphological and Molecular Data Reveal Three Distinct Populations of Indian Wild
      Rice Oryza rufipogon Griff. Species Complex.
AB  - Wild relatives of crops possess adaptive mutations for agronomically important
      traits, which could play significant role in crop improvement for sustainable
      agriculture. However, global climate change and human activities pose serious
      threats to the natural habitats leading to erosion of genetic diversity of wild
      rice populations. The purpose of this study was to explore and characterize
      India's huge untapped wild rice diversity in Oryza rufipogon Griff. species
      complex from a wide range of ecological niches. We made strategic expeditions
      around diversity hot spots in 64 districts of nine different agro-climatic zones
      of the country and collected 418 wild rice accessions. Significant variation was
      observed among the accessions for 46 morphological descriptors, allowing
      classification into O. nivara, O. rufipogon, and O. sativa f. spontanea morpho
      taxonomic groups. Genome-specific pSINE1 markers confirmed all the accessions
      having AA genome, which were further classified using ecotype-specific pSINE1
      markers into annual, perennial, intermediate, and an unknown type. Principal
      component analysis revealed continuous variation for the morphological traits in
      each ecotype group. Genetic diversity analysis based on multi-allelic SSR markers
      clustered these accessions into three major groups and analysis of molecular
      variance for nine agro-climatic zones showed that 68% of the genetic variation
      was inherent amongst individuals while only 11% of the variation separated the
      zones, though there was significant correlation between genetic and spatial
      distances of the accessions. Model based population structure analysis using
      genome wide bi-allelic SNP markers revealed three sub-populations designated 'Pro
      Indica,' 'Pro-Aus,' and 'Mid-Gangetic,' which showed poor correspondence with the
      morpho-taxonomic classification or pSINE1 ecotypes. There was Pan-India
      distribution of the 'Pro-Indica' and 'Pro-Aus' sub-populations across agro
      climatic zones, indicating a more fundamental grouping based on the ancestry
      closely related to 'Indica' and 'Aus' groups of rice cultivars. The Pro-Indica
      population has substantial presence in the Eastern Himalayan Region and Lower
      Gangetic Plains, whereas 'Pro-Aus' sub-population was predominant in the Upper
      Gangetic Plains, Western Himalayan Region, Gujarat Plains and Hills, and Western
      Coastal Plains. In contrast 'Mid-Gangetic' population was largely concentrated in
      the Mid Gangetic Plains. The information presented here will be useful in the
      utilization of wild rice resources for varietal improvement.

PMID- 29467787
TI  - The Effect of Grain Position on Genetic Improvement of Grain Number and Thousand
      Grain Weight in Winter Wheat in North China.
AB  - Genetic improvements have significantly contributed to wheat production. Five
      wheat cultivars-widely grown in north China in the 1950s, 1990s, or 2010s-were
      grown in field experiments conducted in the 2014-2015 and 2015-2016 growing
      seasons. This study evaluated the genetic progress in wheat grain yield and its
      related traits in north China and explored how breeding and selection have
      influenced grain numbers and weights within spikelets in the past 60 years. The
      results showed that the significant increases in grain yield in the past 60 years
      were mainly due to increases in grain number per spike and grain weight, while
      spike number per m2 has not changed significantly. Improvements in thousand grain
      weight (TGW) from the 1950s to 2010s have occurred at four grain positions (G1 to
      G4). The relative contribution of G4 to TGW increased over time, but was much
      less than the contributions of G1, G2, and G3. Indeed, the average grain weight
      at G4 was much less than that of 1000 grains. The increase in grain number per
      spike since the 1950s was mainly due to an increase in grain number at G1, G2 and
      G3, with the relative contribution of grain position to grain number being G1 >
      G2 > G3 > G4. Dwarfing genes increased grain number per spike and grain number at
      G3 and G4, but not TGW. In future, yields could be boosted by enhancing grain
      weight at G4 and grain number at G3 and G4, while maintaining those at G1 and G2.

PMID- 29467786
TI  - Auxin and Gibberellins Are Required for the Receptor-Like Kinase ERECTA Regulated
      Hypocotyl Elongation in Shade Avoidance in Arabidopsis.
AB  - Plants use shade avoidance strategy to escape the canopy shade when grown under
      natural conditions. Previous studies showed that the Arabidopsis receptor-like
      kinase ERECTA (ER) is involved in shade avoidance syndrome. However, the
      mechanisms of ER in modulating SAR by promoting hypocotyl elongation are unknown
      yet. Here, we report that ER regulated hypocotyl elongation in shade avoidance
      requires auxin and gibberellins (GAs). The T-DNA insertional ER mutant er-3 shows
      a less hypocotyl length than that in Col-0 wild type. Promoter::GUS staining
      analysis shows that ER and its paralogous genes ERECTA-LIKE1 (ERL1) and ERECTA
      LIKE2 (ERL2) are differentially expressed in the seedlings, of which only ER is
      most obviously upregulated in the hypocotyl by shade treatment. Exogenous feeding
      assay by using media-application with vertical-grown of Arabidopsis seedlings
      showed that the hypocotyl length of er-3 is partially promoted by indol-3-acetic
      acid (IAA), while it is relatively insensitive of er-3 to various concentrations
      of IAA than that of Col-0. Hypocotyl elongation of er-3 is promoted similar to
      that of Col-0 by high temperature in the white light condition, but the
      elongation was not significantly affected by the treatment of the auxin transport
      inhibitor 1-N-naphthylphthalamic acid (NPA). Exogenous GA3 increased the
      hypocotyl elongation of both er-3 and the wild type in the shade condition, and
      the GA3 biosynthesis inhibitor paclobutrazol (PAC) severely inhibits the
      hypocotyl elongation of Col-0 and er-3. Further analysis showed that auxin
      biosynthesis inhibitors yucasin and L-kynurenine remarkably inhibited the
      hypocotyl elongation of er-3 while yucasin shows a more severe inhibition to er-3
      than Col-0. Relative expression of genes regulating auxin homeostasis and
      signaling, and GA homeostasis is less in er-3 than that in Col-0. Furthermore,
      genetic evidences show that ER regulated hypocotyl elongation is dependent of
      PHYTOCHROME B (PHYB). Overall, we propose that ER regulated shade avoidance by
      promoting hypocotyl elongation is PHYB-dependent and requires auxin and GAs.

PMID- 29467788
TI  - Toxicological and Biochemical Analyses Demonstrate the Absence of Lethal or
      Sublethal Effects of cry1C- or cry2A-Expressing Bt Rice on the Collembolan
      Folsomia candida.
AB  - Assessing the potential effects of insect-resistant genetically engineered (GE)
      plants on collembolans is important because these common soil arthropods may be
      exposed to insecticidal proteins produced in GE plants by ingestion of plant
      residues, crop pollen, or root exudates. Laboratory studies were conducted to
      evaluate the potential effects of two Bacillus thuringiensis (Bt)-rice lines
      expressing Cry1C and Cry2A in pollen and leaves and of their non-Bt conventional
      isolines on the fitness of the collembolan Folsomia candida and on the activities
      of its antioxidant-related enzymes, superoxide dismutase and peroxidase, and of
      its detoxification-related enzymes, glutathione reductase and glutathione S
      transferase. Survival, development, reproduction, and the intrinsic rate of
      increase (rm) were not significantly reduced when F. candida fed on the Bt rice
      pollen or leaf powder than on the non-Bt rice materials; these parameters,
      however, were significantly reduced when F. candida fed on non-Bt rice pollen or
      non-Bt leaf-based diets containing the protease inhibitor E-64 at 75 MUg/g. The
      activities of the antioxidant-related and detoxification-related enzymes in F.
      candida were not significantly affected when F. candida fed on the Bt rice
      materials, but were significantly increased when F. candida fed on the non-Bt
      rice materials containing E-64. The results demonstrate that Cry1C and Cry2A are
      not toxic to F. candida, and also indicate the absence of unintended effects on
      the collembolan caused by any change in plant tissue nutritional composition due
      to foreign gene transformation.

PMID- 29467789
TI  - Tracking Nitrogen Source Using delta15N Reveals Human and Agricultural Drivers of
      Seagrass Degradation across the British Isles.
AB  - Excess nutrients shift the ecological balance of coastal ecosystems, and this
      eutrophication is an increasing problem across the globe. Nutrient levels may be
      routinely measured, but monitoring rarely attempts to determine the source of
      these nutrients, even though bio-indicators are available. Nitrogen stable
      isotope analysis in biota is one such bio-indicator, but across the British
      Isles, this is rarely used. In this study, we provide the first quantitative
      evidence of the anthropogenic drivers of reduced water quality surrounding
      seagrass meadows throughout the British Isles using the stable nitrogen isotope
      delta15N. The values of delta15N ranged from 3.15 to 20.160/00 (Mean +/- SD =
      8.69 +/- 3.500/00), and were high within the Thames Basin suggesting a
      significant influx of urban sewage and livestock effluent into the system. Our
      study provides a rapid 'snapshot' indicating that many seagrass meadows in the
      British Isles are under anthropogenic stress given the widespread inefficiencies
      of current sewage treatment and farming practices. Ten of the 11 seagrass meadows
      sampled are within European marine protected sites. The 10 sites all contained
      seagrass contaminated by nutrients of a human and livestock waste origin leading
      us to question whether generic blanket protection is working for seagrasses in
      the United Kingdom. Infrastructure changes will be required if we are to develop
      strategic wastewater management plans that are effective in the long-term at
      protecting our designated Special Areas of Conservation. Currently, sewage
      pollution is a concealed issue; little information exists and is not readily
      accessible to members of the public.

PMID- 29467790
TI  - Classification of Autism Spectrum Disorder Using Random Support Vector Machine
      Cluster.
AB  - Autism spectrum disorder (ASD) is mainly reflected in the communication and
      language barriers, difficulties in social communication, and it is a kind of
      neurological developmental disorder. Most researches have used the machine
      learning method to classify patients and normal controls, among which support
      vector machines (SVM) are widely employed. But the classification accuracy of SVM
      is usually low, due to the usage of a single SVM as classifier. Thus, we used
      multiple SVMs to classify ASD patients and typical controls (TC). Resting-state
      functional magnetic resonance imaging (fMRI) data of 46 TC and 61 ASD patients
      were obtained from the Autism Brain Imaging Data Exchange (ABIDE) database. Only
      84 of 107 subjects are utilized in experiments because the translation or
      rotation of 7 TC and 16 ASD patients has surpassed +/-2 mm or +/-2 degrees . Then
      the random SVM cluster was proposed to distinguish TC and ASD. The results show
      that this method has an excellent classification performance based on all the
      features. Furthermore, the accuracy based on the optimal feature set could reach
      to 96.15%. Abnormal brain regions could also be found, such as inferior frontal
      gyrus (IFG) (orbital and opercula part), hippocampus, and precuneus. It is
      indicated that the method of random SVM cluster may apply to the auxiliary
      diagnosis of ASD.

PMID- 29467792
TI  - Evaluation of Bioinformatics Approaches for Next-Generation Sequencing Analysis
      of microRNAs with a Toxicogenomics Study Design.
AB  - MicroRNAs (miRNAs) are key post-transcriptional regulators that affect protein
      translation by targeting mRNAs. Their role in disease etiology and toxicity are
      well recognized. Given the rapid advancement of next-generation sequencing
      techniques, miRNA profiling has been increasingly conducted with RNA-seq, namely
      miRNA-seq. Analysis of miRNA-seq data requires several steps: (1) mapping the
      reads to miRBase, (2) considering mismatches during the hairpin alignment
      (windowing), and (3) counting the reads (quantification). The choice made in each
      step with respect to the parameter settings could affect miRNA quantification,
      differentially expressed miRNAs (DEMs) detection and novel miRNA identification.
      Furthermore, these parameters do not act in isolation and their joint effects
      impact miRNA-seq results and interpretation. In toxicogenomics, the variation
      associated with parameter setting should not overpower the treatment effect (such
      as the dose/time-dependent effect). In this study, four commonly used miRNA-seq
      analysis tools (i.e., miRDeep2, miRExpress, miRNAkey, sRNAbench) were
      comparatively evaluated with a standard toxicogenomics study design. We tested 30
      different parameter settings on miRNA-seq data generated from thioacetamide
      treated rat liver samples for three dose levels across four time points, followed
      by four normalization options. Because both miRExpress and miRNAkey yielded
      larger variation than that of the treatment effects across multiple parameter
      settings, our analyses mainly focused on the side-by-side comparison between
      miRDeep2 and sRNAbench. While the number of miRNAs detected by miRDeep2 was
      almost the subset of those detected by sRNAbench, the number of DEMs identified
      by both tools was comparable under the same parameter settings and normalization
      method. Change in the number of nucleotides out of the mature sequence in the
      hairpin alignment (window option) yielded the largest variation for miRNA
      quantification and DEMs detection. However, such a variation is relatively small
      compared to the treatment effect when the study focused on DEMs that are more
      critical to interpret the toxicological effect. While the normalization methods
      introduced a large variation in DEMs, toxic behavior of thioacetamide showed
      consistency in the trend of time-dose responses. Overall, miRDeep2 was found to
      be preferable over other choices when the window option allowed up to three
      nucleotides from both ends.

PMID- 29467791
TI  - Next Generation Sequencing Methods for Diagnosis of Epilepsy Syndromes.
AB  - Epilepsy is a neurological disorder characterized by an increased predisposition
      for seizures. Although this definition suggests that it is a single disorder,
      epilepsy encompasses a group of disorders with diverse aetiologies and outcomes.
      A genetic basis for epilepsy syndromes has been postulated for several decades,
      with several mutations in specific genes identified that have increased our
      understanding of the genetic influence on epilepsies. With 70-80% of epilepsy
      cases identified to have a genetic cause, there are now hundreds of genes
      identified to be associated with epilepsy syndromes which can be analyzed using
      next generation sequencing (NGS) techniques such as targeted gene panels, whole
      exome sequencing (WES) and whole genome sequencing (WGS). For effective use of
      these methodologies, diagnostic laboratories and clinicians require information
      on the relevant workflows including analysis and sequencing depth to understand
      the specific clinical application and diagnostic capabilities of these gene
      sequencing techniques. As epilepsy is a complex disorder, the differences
      associated with each technique influence the ability to form a diagnosis along
      with an accurate detection of the genetic etiology of the disorder. In addition,
      for diagnostic testing, an important parameter is the cost-effectiveness and the
      specific diagnostic outcome of each technique. Here, we review these commonly
      used NGS techniques to determine their suitability for application to epilepsy
      genetic diagnostic testing.

PMID- 29467793
TI  - Decomposing Additive Genetic Variance Revealed Novel Insights into Trait
      Evolution in Synthetic Hexaploid Wheat.
AB  - Whole genome duplication (WGD) is an evolutionary phenomenon, which causes
      significant changes to genomic structure and trait architecture. In recent years,
      a number of studies decomposed the additive genetic variance explained by
      different sets of variants. However, they investigated diploid populations only
      and none of the studies examined any polyploid organism. In this research, we
      extended the application of this approach to polyploids, to differentiate the
      additive variance explained by the three subgenomes and seven sets of
      homoeologous chromosomes in synthetic allohexaploid wheat (SHW) to gain a better
      understanding of trait evolution after WGD. Our SHW population was generated by
      crossing improved durum parents (Triticum turgidum; 2n = 4x = 28, AABB
      subgenomes) with the progenitor species Aegilops tauschii (syn Ae. squarrosa, T.
      tauschii; 2n = 2x = 14, DD subgenome). The population was phenotyped for 10
      fungal/nematode resistance traits as well as two abiotic stresses. We showed that
      the wild D subgenome dominated the additive effect and this dominance affected
      the A more than the B subgenome. We provide evidence that this dominance was not
      inflated by population structure, relatedness among individuals or by longer
      linkage disequilibrium blocks observed in the D subgenome within the population
      used for this study. The cumulative size of the three homoeologs of the seven
      chromosomal groups showed a weak but significant positive correlation with their
      cumulative explained additive variance. Furthermore, an average of 69% for each
      chromosomal group's cumulative additive variance came from one homoeolog that had
      the highest explained variance within the group across all 12 traits. We
      hypothesize that structural and functional changes during diploidization may
      explain chromosomal group relations as allopolyploids keep balanced dosage for
      many genes. Our results contribute to a better understanding of trait evolution
      mechanisms in polyploidy, which will facilitate the effective utilization of
      wheat wild relatives in breeding.

PMID- 29467794
TI  - Detection of Potential Problematic Cytb Gene Sequences of Fishes in GenBank.
AB  - Fishes are, by far, the most diverse group of vertebrates. Their classification
      relies heavily on morphology. In practice, the correct morphological
      identification of species often depends on personal experience because many
      species vary in their body shape, color and other external characters. Thus, the
      identification of a species may be prone to errors. Due to the rapid development
      of molecular biology, the number of sequences of fishes deposited in GenBank has
      grown explosively. These published data likely contain errors owing to invalid or
      incorrectly identified species. The erroneous data can lead to downstream
      problems. Thus, it is critical that such errors get identified and corrected. A
      strategy based on DNA barcoding can detect potentially erroneous data, especially
      when intraspecific K2P variation exceeds interspecific K2P divergence. Analyses
      of the most used DNA marker for fishes (mitochondrial Cytb) discovers that
      intraspecific differences of fishes are generally less than 1%, while
      interspecific differences are generally higher than 10%. Based on this ruler, our
      analyses identify 1,303 potential problematic Cytb sequences of fishes in GenBank
      and point to taxonomic problems, errors in identification, genetic introgression
      and other concerns. Care must be taken to avoid the perpetuation of errors when
      using these available data.

PMID- 29467795
TI  - Genome-Wide Study of YABBY Genes in Upland Cotton and Their Expression Patterns
      under Different Stresses.
AB  - Members of the YABBY gene family, a small plant-specific family of genes, have
      been proposed to function in specifying abaxial cell fate. Although to date
      little has been learned about cotton YABBY genes, completion of the cotton genome
      enables a comprehensive genome-wide analysis of YABBY genes in cotton. Here, a
      total of 12, 12, and 23 YABBY genes were identified in Gossypium arboreum (2n =
      26, A2), G. raimondii (2n = 26, D5), and G. hirsutum (2n = 4x = 52, [AD]t),
      respectively. Sequence analysis showed that the N-terminal zinc-finger and C
      terminal YABBY domains in YABBY proteins are highly conserved among cotton,
      Arabidopsis, and rice. Eighty-five genes from eight sequenced species naturally
      clustered into five groups, and the YAB2-like group could be divided into three
      sub-groups, indicating that YABBYs are highly conserved among the examined
      species. Orthologs from the At and Dt sub-genomes (where "t" indicates
      tetraploid) showed good collinearity, indicating that YABBY loci are highly
      conserved between these two sub-genomes. Whole-genome duplication was the primary
      cause of upland cotton YABBY gene expansion, segmental duplication played
      important roles in YABBY gene expansion within the At and Dt sub-genomes, and the
      YAB5-like group was mainly generated by segmental duplication. The long-terminal
      repeat retroelements Copia and Gypsy were identified as major transposable
      elements accompanying the appearance of duplicated YABBY genes, suggesting that
      transposable element expansion might be involved in gene duplication. Selection
      pressure analyses using PAML revealed that relaxed purifying selection might be
      the main impetus during evolution of YABBY genes in the examined species.
      Furthermore, exon/intron pattern and motif analyses indicated that genes within
      the same group were significantly conserved between Arabidopsis and cotton. In
      addition, the expression patterns in different tissues suggest that YABBY
      proteins may play roles in ovule development because YABBYs are highly expressed
      in ovules. The expression pattern of YABBY genes showed that approximately half
      of the YABBYs were down-regulated under different stress treatments.
      Collectively, our results represent a comprehensive genome-wide study of the
      YABBY gene family, which should be helpful in further detailed studies on the
      gene function and evolution of YABBY genes in cotton.

PMID- 29467796
TI  - Biochemical characterization of a phospholipase A2 homologue from the venom of
      the social wasp Polybia occidentalis.
AB  - Background: Wasp venoms constitute a molecular reservoir of new pharmacological
      substances such as peptides and proteins, biological property holders, many of
      which are yet to be identified. Exploring these sources may lead to the discovery
      of molecules hitherto unknown. This study describes, for the first time in
      hymenopteran venoms, the identification of an enzymatically inactive
      phospholipase A2 (PLA2) from the venom of the social wasp Polybia occidentalis.
      Methods: P. occidentalis venom was fractioned by molecular exclusion and reverse
      phase chromatography. For the biochemical characterization of the protein, 1D and
      2D SDS-PAGE were performed, along with phospholipase activity assays on synthetic
      substrates, MALDI-TOF mass spectrometry and sequencing by Edman degradation.
      Results: The protein, called PocTX, was isolated using two chromatographic steps.
      Based on the phospholipase activity assay, electrophoresis and mass spectrometry,
      the protein presented a high degree of purity, with a mass of 13,896.47 Da and a
      basic pI. After sequencing by the Edman degradation method, it was found that the
      protein showed a high identity with snake venom PLA2 homologues. Conclusion: This
      is the first report of an enzymatically inactive PLA2 isolated from wasp venom,
      similar to snake PLA2 homologues.

PMID- 29467797
TI  - Peptidomic investigation of Neoponera villosa venom by high-resolution mass
      spectrometry: seasonal and nesting habitat variations.
AB  - Background: Advancements in proteomics, including the technological improvement
      in instrumentation, have turned mass spectrometry into an indispensable tool in
      the study of venoms and toxins. In addition, the advance of nanoscale liquid
      chromatography coupled to nanoelectrospray mass spectrometry allows, due to its
      high sensitivity, the study of venoms from species previously left aside, such as
      ants. Ant venoms are a complex mixture of compounds used for defense, predation
      or communication purposes. The venom from Neoponera ants, a genus restricted to
      Neotropical regions, is known to have cytolytic, hemolytic, antimicrobial and
      insecticidal activities. Moreover, venoms from several Neoponera species have
      been compared and differences in their toxicity related to nesting habitat
      variation were reported. Therefore, the present study aimed to perform a deep
      peptidomic analysis of Neoponera villosa venom and a comparison of seasonal and
      nesting habitat variations using high-resolution mass spectrometry. Methods:
      Specimens of N. villosa ants were captured in Panga Natural Reserve (Uberlandia,
      MG, Brazil) from arboreal and ground-dwelling nests during summer and winter
      time. The venom glands were dissected, pooled and disrupted by ultra-sonic waves.
      The venom collected from different habitats (arboreal and ground-dwelling) and
      different seasons (summer and winter) was injected into a nanoACQUITY ULPC
      hyphened to a Q-Exactive Orbitrap mass spectrometer. The raw data were analyzed
      using PEAKS 7. Results: The results showed a molecular diversity of more than 500
      peptides among these venoms, mostly in the mass range of 800-4000 Da. Mutations
      and post-translational modifications were described and differences among the
      venoms were observed. Part of the peptides matched with ponericins, a well-known
      antimicrobial peptide family. In addition, smaller fragments related to
      ponericins were also identified, suggesting that this class of antimicrobial
      peptide might undergo enzymatic cleavages. Conclusion: There are substantial
      differences among the venom of N. villosa ants collected in different seasons and
      from different nest habitats. The venom composition is affected by climate
      changes that influence prey availability and predator presence. Clearly, nano-LC
      MS boosted the knowledge about ant venom, a rich source of unexplored and
      promising bioactive compounds.

PMID- 29467798
TI  - Female nursing partner choice in a population of wild house mice (Mus musculus
      domesticus).
AB  - Abstract:  Background: Communal nursing in house mice is an example of
      cooperation where females pool litters in the same nest and indiscriminately
      nurse own and other offspring despite potential exploitation. The direct fitness
      benefits associated with communal nursing shown in laboratory studies suggest it
      to be a selected component of female house mice reproductive behaviour. However,
      past studies on communal nursing in free-living populations have debated whether
      it is a consequence of sharing the same nest or an active choice. Here using data
      from a long-term study of free-living, wild house mice we investigated individual
      nursing decisions and determined what factors influenced a female's decision to
      nurse communally. Results: Females chose to nurse solitarily more often than
      expected by chance, but the likelihood of nursing solitarily decreased when
      females had more partners available. While finding no influence of pairwise
      relatedness on partner choice, we observed that females shared their social
      environment with genetically similar individuals, suggesting a female's home area
      consisted of related females, possibly facilitating the evolution of cooperation.
      Within such a home area females were more likely to nest communally when the
      general relatedness of her available options was relatively high. Females formed
      communal nests with females that were familiar through previous associations and
      had young pups of usually less than 5 days old. Conclusions: Our findings suggest
      that communal nursing was not a by-product of sharing the same nesting sites, but
      females choose communal nursing partners from a group of genetically similar
      females, and ultimately the decision may then depend on the pool of options
      available. Social partner choice proved to be an integrated part of cooperation
      among females, and might allow females to reduce the conflict over number of
      offspring in a communal nest and milk investment towards own and other offspring.
      We suggest that social partner choice may be a general mechanism to stabilize
      costly cooperation.

PMID- 29467799
TI  - Exposure to maternal cafeteria diets during the suckling period has greater
      effects on fat deposition and Sterol Regulatory Element Binding Protein-1c (SREBP
      1c) gene expression in rodent offspring compared to exposure before birth.
AB  - Background: While the adverse metabolic effects of exposure to obesogenic diets
      during both the prenatal and early postnatal period are well established, the
      relative impact of exposure during these separate developmental windows remains
      unclear. This study aimed to assess the relative contribution of exposure to a
      maternal cafeteria diet during pregnancy and lactation on body weight, fat mass
      and expression of lipogenic and adipokine genes in the offspring. Methods: Wistar
      rats were fed either a control chow (Control, n = 14) or obesogenic cafeteria
      diet (CAF, n = 12) during pregnancy and lactation. Pups were cross-fostered to
      another dam in either the same or different dietary group within 24 h of birth.
      Body weight, body fat mass and expression of lipogenic and adipokine genes in
      subcutaneous and visceral adipose tissues were determined in offspring at weaning
      and 3 weeks post-weaning. Results: Offspring suckled by CAF dams had a lower body
      weight (P < 0.05), but ~ 2-fold higher percentage body fat at weaning than
      offspring suckled by Control dams (P < 0.01), independent of whether they were
      born to a Control or CAF dam. At 6 weeks of age, after all offspring were weaned
      onto standard chow, males and females suckled by CAF dams remained lighter (P <
      0.05) than offspring suckled by Control dams, but the percentage fat mass was no
      longer different between groups. Sterol Regulatory Element Binding Protein-1c
      (SREBP-1c) mRNA expression was ~ 25% lower in offspring suckled by cafeteria dams
      in males at weaning (P < 0.05) and in females at 6 weeks of age (P < 0.05).
      Exposure to a cafeteria diet during the suckling period alone also resulted in
      increased adipocyte Peroxisome Proliferator Activated Receptor-gamma (PPAR-gamma)
      mRNA expression in females, and adiponectin and leptin mRNA expression in both
      sexes at weaning. Conclusions: The findings from this study point to the critical
      role of the suckling period for deposition of adipose tissue in rodents, and the
      potential role of altered adipocyte gene expression in mediating these effects.

PMID- 29467801
TI  - Neuro-Ophthalmology and EUNOS are reunited.

PMID- 29467802
TI  - Amiodarone-associated Optic Neuropathy-A Clinical Criteria-based Diagnosis?
AB  - Amiodarone-associated optic neuropathy (AAON) is a controversial diagnosis with
      possible impact on vital cardiac therapy decisions. This retrospective case
      series aims for application of distinguishing features of AAON versus non
      arteritic ischaemic optic neuropathy (NAION): Bilaterality, mode of onset, degree
      of optic nerve dysfunction, structure of uninvolved disc (unilateral cases), and
      systemic toxic effects. Applying these criteria to patients with disc swelling
      under amiodarone, the authors identified four unilateral disc swellings, one with
      NAION-typical features only and three with one or more NAION-atypical features.
      All three sequential and six bilateral cases showed one or more NAION-atypical
      features. The 12 cases highlight the persisting diagnostic dilemma arising from
      diversity of presentation, lack of plausible pathomechanism, and controversial
      existence of the entity itself.

PMID- 29467800
TI  - Resting metabolic rate of obese patients under very low calorie ketogenic diet.
AB  - Background: The resting metabolic rate (RMR) decrease, observed after an obesity
      reduction therapy is a determinant of a short-time weight regain. Thus, the
      objective of this study was to evaluate changes in RMR, and the associated
      hormonal alterations in obese patients with a very low-calorie ketogenic (VLCK)
      diet induced severe body weight (BW) loss. Method: From 20 obese patients who
      lost 20.2 kg of BW after a 4-months VLCK-diet, blood samples and body composition
      analysis, determined by DXA and MF-Bioimpedance, and RMR by indirect calorimetry,
      were obtained on four subsequent visits: visit C-1, basal, initial fat mass (FM)
      and free fat mass (FFM); visit C-2, - 7.2 kg in FM, - 4.3 kg in FFM, maximal
      ketosis; visit C-3, - 14.4 kg FM, - 4.5 kg FFM, low ketosis; visit C-4, - 16.5 kg
      FM, - 3.8 kg FFM, no ketosis. Each subject acted as his own control. Results:
      Despite the large BW reduction, measured RMR varied from basal visit C-1 to visit
      C-2, - 1.0%; visit C-3, - 2.4% and visit C-4, - 8.0%, without statistical
      significance. No metabolic adaptation was observed. The absent reduction in RMR
      was not due to increased sympathetic tone, as thyroid hormones, catecholamines,
      and leptin were reduced at any visit from baseline. Under regression analysis
      FFM, adjusted by levels of ketonic bodies, was the only predictor of the RMR
      changes (R2 = 0.36; p < 0.001). Conclusion: The rapid and sustained weight and FM
      loss induced by VLCK-diet in obese subjects did not induce the expected reduction
      in RMR, probably due to the preservation of lean mass. Trial registration: This
      is a follow up study on a published clinical trial.

PMID- 29467803
TI  - Vogt-Koyanagi-Harada Disease Presenting as Unilateral Neuroretinits.
AB  - A 42-year-old female presented with unilateral visual loss associated with
      systemic symptoms of fever and headache. Although initial ophthalmic examination
      revealed a unilateral neuroretinitis, investigation for infectious and non
      infectious causes of neuroretinitis were negative. At our examination, retinal
      imaging (suggestive of bilateral involvement) along with the results of lumbar
      puncture (pleocytosis) and clinical findings was consistent with a diagnosis of
      Vogt-Koyanagi-Harada disease. The patient was treated with intravenous steroids
      with prompt resolution of her symptoms. Vogt-Koyanagi-Harada disease may present
      atypically and should be considered in the differential diagnosis of
      neuroretinitis.

PMID- 29467804
TI  - Clinical Evaluation and Treatment Outcome of Traumatic Optic Neuropathy in Nepal:
      A Retrospective Case Series.
AB  - This study aims to report the clinical features and role of different treatment
      modalities in final visual outcome in traumatic optic neuropathy (TON). The
      authors retrospectively reviewed the records of patients with TON over 4 years.
      There were 37 patients of unilateral TON. Mean age was 28.70 +/- 15.20 years
      (range: 8-90) and 89% (n = 33) were males. Road traffic accident was the common
      cause (43.2%), followed by fall injury (35.1%). There was improvement of visual
      acuity in 51.4% (n = 19) cases. Out of different treatment modalities, high-dose
      intravenous methylprednisolone (1 g/day) led to significant improvement in final
      visual acuity (p = 0.013). There was no significant improvement in final visual
      outcome in patients with poor initial visual acuity and those with intracranial
      injuries.

PMID- 29467805
TI  - Reduction of Optic Disc Oedema by Bortezomib and Dexamethasone Followed by
      Autologous Peripheral Blood Stem Cell Transplantation in Patient with POEMS
      Syndrome.
AB  - The authors present findings in a 39-year-old man with polyneuropathy,
      organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS)
      syndrome with bilateral optic disc oedema. He was successfully treated with
      bortezomib and dexamethasone followed by autologous peripheral blood stem cell
      transplantation. The peripapillary retinal thickness was reduced in the optical
      coherence tomographic (OCT) images along with a decrease of the serum vascular
      endothelial growth factor (VEGF) levels. The authors recommend OCT to monitor the
      changes in the signs of POEMS syndrome after treatments.

PMID- 29467806
TI  - Isolated Abducens Palsy Heralding Occult Human Immunodeficiency Virus-Related
      Lymphoma.
AB  - A 40-year-old African American man with recently diagnosed Human Immunodeficiency
      Virus (HIV) presented with isolated left abducens palsy. Initial neuro-imaging
      and laboratory evaluation, including cerebrospinal fluid (CSF) analysis, were
      unremarkable. Continued search for causative aetiology revealed systemic lymphoma
      diagnosed ultimately by bone marrow biopsy. Systemic lymphoma is commonly
      encountered in the HIV patient population, but presentation can be unusual and
      has been seen, albeit rarely, in the setting of isolated cranial neuropathy. This
      case demonstrates the often diligent investigation required in the setting of
      isolated cranial neuropathies in patients with HIV.

PMID- 29467807
TI  - Temporary Visual Loss Due to Posterior Reversible Encephalopathy Syndrome in the
      Case of an End-Stage Renal Disease Patient.
AB  - Posterior reversible encephalopathy syndrome is a clinical phenomenon associated
      with headache, altered mental status, seizures, and visual disturbances along
      with radiographic acute cerebral oedema. Several conditions are correlated with
      posterior reversible encephalopathy syndrome, with acute hypertension, eclampsia,
      and cytotoxic agents being the most common. This report presents a case of
      posterior reversible encephalopathy syndrome in a 45-year-old male with multiple
      underlying conditions, including hypertension, diabetes, and end-stage renal
      disease. Sudden onset of bilateral visual loss with mild systemic feature of
      dizziness was noted on presentation. Radiologic findings showed characteristic
      findings of posterior reversible encephalopathy syndrome. Following prompt
      control of hypertension and haemodialysis, resolution of symptoms was noted.

PMID- 29467808
TI  - Sibling Ethambutol Optic Chiasmopathy.
AB  - Ethambutol is utilised in the treatment of Mycobacterium avium and Mycobacterium
      tuberculosis infection. The authors report two siblings who developed the adverse
      effect of ethambutol-induced optic chiasmopathy, with recovery following
      cessation of ethambutol. Discussion explores potential genetic predisposition to
      development of this condition and its resolution. Ethambutol optic neuropathy
      (EON), Leber's hereditary optic neuropathy (LHON), and other optic neuropathies
      of mitochondrial origin share a common pathophysiology. Consequently, the authors
      postulate treatments utilised in LHON, including vitamin B supplementation and
      idebenone, may have benefit in EON. This article presents concepts for further
      research, suggesting a potential genetic susceptibility to EON and its treatment.

PMID- 29467809
TI  - Intermittent Ocular Microflutter in a Patient with Acute-Onset Oscillopsia.
AB  - Saccadic intrusions are small involuntary saccadic movements that disrupt visual
      fixation. Among saccadic intrusions without intersaccadic intervals, ocular
      flutter and opsoclonus are prominent. The saccade amplitude can occasionally be
      very small, which is referred to as ocular microflutter. The authors present a
      patient with acute-onset oscillopsia following a non-specific viral condition. An
      ocular microflutter was subsequently detected using video-oculography. After
      extensive investigation, a diagnosis of isolated idiopathic or post-viral ocular
      microflutter was made. The evolution of the condition was favourable, and the
      progressive improvement of oscillopsia occurred during the following months;
      however, complete resolution was not achieved. Ocular microflutter is a saccadic
      intrusion that is rarely described in the literature and is likely go clinically
      unnoticed because of its small amplitude and the rare use of video-oculography in
      daily practice. In patients in whom this condition is suspected, the use of video
      oculography is essential for a correct diagnosis.

PMID- 29467810
TI  - Brown Syndrome Following Upper Eyelid Ptosis Repair.
AB  - Brown syndrome is characterised by impaired supraduction worse in adduction due
      to a restricted superior oblique tendon passing through the trochlea. A few
      reports have previously described Brown syndrome after upper eyelid surgery,
      including blepharoplasty and ptosis repair. The authors describe two additional
      cases of Brown syndrome following ptosis repair. The first case is a 65-year-old
      woman with new-onset vertical binocular diplopia following bilateral levator
      advancement surgery. Ocular motility examination demonstrated moderate impairment
      of elevation in adduction. The second case is a 35-year-old woman who presented
      with new-onset intermittent binocular diplopia following right upper lid ptosis
      repair. Examination revealed large vertical fusional amplitudes and a large left
      intermittent hyperphoria in an alignment pattern consistent with Brown syndrome.
      Despite presenting after surgery, these cases differ in mechanism. The first case
      likely occurred due to intraoperative impairment of the superior oblique tendon
      sheath or trochlea, whereas the second case represented an unmasking of a long
      standing, previous vertical strabismus that was consistent with a Brown syndrome
      pattern.

PMID- 29467811
TI  - Report on the 13th European Neuro-Ophthalmology Society Meeting by the Congress
      Chair.

PMID- 29467812
TI  - Prelacteal feeding and associated factors among newborns in rural Sidama, south
      Ethiopia: a community based cross-sectional survey.
AB  - Background: The practice of giving prelacteal feeds deprive a newborn of valuable
      nutrients and expose the newborn to risks of infection. Despite its negative
      health outcomes, prelacteal feeding prevails in Ethiopia. Therefore, the current
      study was undertaken to assess the prevalence of prelacteal feeding practices and
      its associated factors in a rural community in south Ethiopia. Methods: We
      conducted a community based cross-sectional study of 597 mothers of children aged
      less than six months. Mothers were selected using a multistage cluster sampling
      technique from Hawela Tula, a rural catchment under Hawassa City Administration.
      Newborns exposed to any foods, substances or drinks other than human milk before
      the initiation of breastfeeding or during the first three days of birth were
      regarded as receiving prelacteal feeds. Descriptive summaries were done to
      present the main findings; bivariate and multivariate logistic regression
      analyses were undertaken to identify variables associated with prelacteal feeding
      practices. Results: Among the total infants, 25.5% (95% confidence interval [CI]
      23.5%, 27.5%) were found to be exposed to prelacteal feeds. Boiled water (36.8%)
      and fresh butter (32.2%) were the top two prelacteal foods. The prevalence of
      prelacteal feeding was higher among infants whose mothers are housewives, and
      among infants born to mothers aged between 21 and 34 years. Almost two-third
      (64.3%) of mothers who exposed their newborn to prelacteal feeds did so with
      advice from their parents. Mothers who had poor knowledge on breastfeeding were
      nine times more likely to practice prelacteal feeding compared to those with good
      knowledge (adjusted odds ratio [AOR] 8.9, 95% CI 4.2, 18.7). Lack of knowledge on
      the risks associated with prelacteal feeding (AOR 6.8; 95% CI 2.6, 17.8) and
      misconceptions about breastfeeding (AOR 8.1; 95% CI 3.9, 16.6) were associated
      with prelacteal feeding. However, mothers' place of delivery and attendance at
      breastfeeding counseling sessions showed no association with the practice of
      prelacteal feeding. Conclusions: Prelacteal feeding is commonly practiced in the
      study area. Raising women's awareness on the consequences of prelacteal feeding
      is warranted. Involving parents of women when promoting optimal infant feeding
      practices should be emphasized.

PMID- 29467814
TI  - Fast phylogenetic inference from typing data.
AB  - Background: Microbial typing methods are commonly used to study the relatedness
      of bacterial strains. Sequence-based typing methods are a gold standard for
      epidemiological surveillance due to the inherent portability of sequence and
      allelic profile data, fast analysis times and their capacity to create common
      nomenclatures for strains or clones. This led to development of several novel
      methods and several databases being made available for many microbial species.
      With the mainstream use of High Throughput Sequencing, the amount of data being
      accumulated in these databases is huge, storing thousands of different profiles.
      On the other hand, computing genetic evolutionary distances among a set of typing
      profiles or taxa dominates the running time of many phylogenetic inference
      methods. It is important also to note that most of genetic evolution distance
      definitions rely, even if indirectly, on computing the pairwise Hamming distance
      among sequences or profiles. Results: We propose here an average-case linear-time
      algorithm to compute pairwise Hamming distances among a set of taxa under a given
      Hamming distance threshold. This article includes both a theoretical analysis and
      extensive experimental results concerning the proposed algorithm. We further show
      how this algorithm can be successfully integrated into a well known phylogenetic
      inference method, and how it can be used to speedup querying local phylogenetic
      patterns over large typing databases.

PMID- 29467813
TI  - Subunits of human condensins are potential therapeutic targets for cancers.
AB  - The main role of condensins is to regulate chromosome condensation and
      segregation during cell cycles. Recently, it has been suggested in the
      literatures that subunits of condensin I and condensin II are involved in some
      human cancers. This paper will first briefly discuss discoveries of human
      condensins, their components and structures, and their multiple cellular
      functions. This will be followed by reviews of most recent studies on subunits of
      human condensins and their dysregulations or mutations in human cancers. It can
      be concluded that many of these subunits have potentials to be novel targets for
      cancer therapies. However, hCAP-D2, a subunit of human condensin I, has not been
      directly documented to be associated with any human cancers to date. This review
      hypothesizes that hCAP-D2 can also be a potential therapeutic target for human
      cancers, and therefore that all subunits of human condensins are potential
      therapeutic targets for human cancers.

PMID- 29467815
TI  - Derivative-free neural network for optimizing the scoring functions associated
      with dynamic programming of pairwise-profile alignment.
AB  - Background: A profile-comparison method with position-specific scoring matrix
      (PSSM) is among the most accurate alignment methods. Currently, cosine similarity
      and correlation coefficients are used as scoring functions of dynamic programming
      to calculate similarity between PSSMs. However, it is unclear whether these
      functions are optimal for profile alignment methods. By definition, these
      functions cannot capture nonlinear relationships between profiles. Therefore, we
      attempted to discover a novel scoring function, which was more suitable for the
      profile-comparison method than existing functions, using neural networks.
      Results: Although neural networks required derivative-of-cost functions, the
      problem being addressed in this study lacked them. Therefore, we implemented a
      novel derivative-free neural network by combining a conventional neural network
      with an evolutionary strategy optimization method used as a solver. Using this
      novel neural network system, we optimized the scoring function to align remote
      sequence pairs. Our results showed that the pairwise-profile aligner using the
      novel scoring function significantly improved both alignment sensitivity and
      precision relative to aligners using existing functions. Conclusions: We
      developed and implemented a novel derivative-free neural network and aligner
      (Nepal) for optimizing sequence alignments. Nepal improved alignment quality by
      adapting to remote sequence alignments and increasing the expressiveness of
      similarity scores. Additionally, this novel scoring function can be realized
      using a simple matrix operation and easily incorporated into other aligners.
      Moreover our scoring function could potentially improve the performance of
      homology detection and/or multiple-sequence alignment of remote homologous
      sequences. The goal of the study was to provide a novel scoring function for
      profile alignment method and develop a novel learning system capable of
      addressing derivative-free problems. Our system is capable of optimizing the
      performance of other sophisticated methods and solving problems without
      derivative-of-cost functions, which do not always exist in practical problems.
      Our results demonstrated the usefulness of this optimization method for
      derivative-free problems.

PMID- 29467817
TI  - Mental health literacy: what do Nigerian adolescents know about depression?
AB  - Background: Depression is a leading cause of disability and has been projected to
      become the 2nd most burdensome disease by the year 2020; depression has also been
      found to be the strongest single risk factor for attempted or completed suicides.
      Adolescent-onset mood disorders are frequently unrecognized or misdiagnosed and
      often go untreated. While there is a growing literature on the mental health
      literacy of adults, there has not been a parallel interest in the mental health
      literacy of young people in Nigeria. Methods: The study was a cross-sectional
      descriptive survey conducted among students of a Federal Government College (high
      school) in south-east Nigeria. All consenting students in the senior secondary
      classes (grades 10-12) were recruited, making a total of 285 participants. The
      participants were presented with the 'friend in need' questionnaire designed to
      elicit the participants' recognition of the disorder depicted in two vignettes
      and their recommendation about the appropriate source of help-seeking. One
      vignette was of a clinically depressed case while the other vignette was about a
      girl undergoing normal life crisis. Results: Out of the 285 students recruited
      into the study, 277 questionnaires were adequately completed indicating a
      response rate of 97.2%. A total of 4.8% (n = 13) participants correctly
      identified and labelled the depression vignette. Only four respondents (1.5%)
      recommended professional help from a Psychiatrist or Psychologist. Insomnia was
      the most identified symptom of distress for depression (17.1%). Females
      demonstrated higher mental health literacy, in terms of their ability to
      correctly label the depression vignettes, their expression of greater concern
      over a depressed peer than males, their expectation that depression requires a
      longer recovery than normal teenage problems and in their ability to identify
      individual symptoms of depression. Family and friends were the most recommended
      source of help. Conclusion: Mental health literacy was abysmally low amongst the
      adolescents surveyed. There's an urgent need to increase mental health awareness
      in Nigeria.

PMID- 29467816
TI  - Advanced gallbladder inflammation is a risk factor for gallbladder perforation in
      patients with acute cholecystitis.
AB  - Background: Acute perforated cholecystitis (APC) is probably the most severe
      benign gallbladder pathology with high rates of morbidity and mortality. The
      cause of APC has not been fully understood. We postulated that APC is a
      complication of advanced gallbladder inflammation. The aim of this study was to
      investigate the extent of gallbladder inflammation in patients with APC. Methods:
      Patients with intraoperative and histopathologic diagnosis of APC were compared
      with cases with acute cholecystitis without perforation with respect to the
      extent of inflammation on histopathology as well as surgical outcomes. Results:
      Fifty patients with APC were compared to 150 cases without perforation. Advanced
      age > 65 years and elevated CRP were confirmed on multivariate analysis as
      independent risk factors for APC. Advanced gallbladder inflammation was seen
      significantly more often in patients with APC (84.0 vs. 18.7%). Surgery lasted
      significantly longer 131.3 +/- 55.2 min vs. 100.4 +/- 47.9 min; the rates of
      conversion (22 vs. 4%), morbidity (24 vs. 7%), and mortality (8 vs. 1%) were
      significantly higher in patients with APC. ICU management following surgery was
      needed significantly more often in the APC group (56 vs. 15%), and the overall
      length of stay (11.2 +/- 12.0 days vs. 5.8 +/- 6.5 days) was significantly longer
      compared to the group without perforation. Conclusion: Acute gallbladder
      perforation in patients with acute cholecystitis represents the most severe
      complication of cholecystitis. Acute perforated cholecystitis is a sequela of
      advanced gallbladder inflammation like empyematous and gangrenous cholecystitis
      and is associated with poor outcome compared to non-perforated cases.

PMID- 29467818
TI  - Knowledge transfer: a worldwide challenge in child mental health: a
      recommendation to the readership of CAPMH concerning the revised version of the
      IACAPAP Textbook of Child and Adolescent Mental Health.
AB  - Background: Transfer of knowledge is an important issue throughout all scientific
      disciplines, especially in the medical and psycho-social field. The issue of
      worldwide knowledge transfer in child mental health is one of the aims and goals
      of the journal Child and Adolescent Psychiatry and Mental Health (CAPMH). The
      demand for mental health training is high worldwide, and especially in low- to
      lower-middle income countries, where inadequate access to knowledge resources in
      the field of child and adolescent mental health (CAMH) is prevalent. At the same
      time, many of these countries are showing an increased risk for mental health
      issues in children and adolescents. The International Association for Child and
      Adolescent Psychiatry and Allied Professions (IACAPAP) Textbook of Child and
      Adolescent Mental Health counters this problem. It is an open-access e-textbook
      aiming to provide an overview of current and established treatment and practical
      approaches for child and adolescent psychiatrists, psychotherapists and allied
      (mental health) professionals worldwide. First published in 2012, the updated and
      revised version was launched in 2015. The aim of this commentary is to review and
      disseminate the usefulness and practicability of content and further material
      included in the new version of the textbook. Review: Overall, the textbook
      contains ten sections divided into 59 chapters, with a total of 1435 pages. The
      original version of the textbook was written in English. The revised version
      contains translations of 49 chapters into different languages (to date French,
      Spanish, Hebrew, Arabic, Portuguese, Russian, Norwegian and/or Japanese), with
      additional material for knowledge dissemination and self-directed learning (e.g.
      videos and quizzes) for several chapters. The textbook and the add-on materials
      for dissemination are of high quality and convey a great introduction to
      important topics concerning mental health. Apart from knowledge transfer, there
      is a pragmatic focus on clinical practice and on regional and cultural
      differences. Conclusion: The textbook is a new and unique opportunity for
      professionals all over the world to improve their knowledge, skills and expertise
      in CAMH. High-quality, up-to-date and freely accessible materials in the field of
      CAMH are combined with the opportunity to share insights with colleagues.

PMID- 29467819
TI  - Real-time imaging reveals that lytic polysaccharide monooxygenase promotes
      cellulase activity by increasing cellulose accessibility.
AB  - Background: The high cost of enzymes is one of the key technical barriers that
      must be overcome to realize the economical production of biofuels and
      biomaterials from biomass. Supplementation of enzyme cocktails with lytic
      polysaccharide monooxygenase (LPMO) can increase the efficiency of these
      cellulase mixtures for biomass conversion. The previous studies have revealed
      that LPMOs cleave polysaccharide chains by oxidization of the C1 and/or C4
      carbons of the monomeric units. However, how LPMOs enhance enzymatic degradation
      of lignocellulose is still poorly understood. Results: In this study, we combined
      enzymatic assays and real-time imaging using atomic force microscopy (AFM) to
      study the molecular interactions of an LPMO [TrAA9A, formerly known as TrCel61A)
      from Trichoderma reesei] and a cellobiohydrolase I (TlCel7A from T.
      longibrachiatum) with bacterial microcrystalline cellulose (BMCC) as a substrate.
      Cellulose conversion by TlCel7A alone was enhanced from 46 to 54% by the addition
      of TrAA9A. Conversion by a mixture of TlCel7A, endoglucanase, and beta
      glucosidase was increased from 79 to 87% using pretreated BMCC with TrAA9A for 72
      h. AFM imaging demonstrated that individual TrAA9A molecules exhibited
      intermittent random movement along, across, and penetrating into the ribbon-like
      microfibril structure of BMCC, which was concomitant with the release of a small
      amount of oxidized sugars and the splitting of large cellulose ribbons into
      fibrils with smaller diameters. The dividing effect of the cellulose microfibril
      occurred more rapidly when TrAA9A and TlCel7A were added together compared to
      TrAA9A alone; TlCel7A alone caused no separation. Conclusions: TrAA9A increases
      the accessible surface area of BMCC by separating large cellulose ribbons, and
      thereby enhances cellulose hydrolysis yield. By providing the first direct
      observation of LPMO action on a cellulosic substrate, this study sheds new light
      on the mechanisms by which LPMO enhances biomass conversion.

PMID- 29467821
TI  - Function analysis of 5'-UTR of the cellulosomal xyl-doc cluster in Clostridium
      papyrosolvens.
AB  - Background: Anaerobic, mesophilic, and cellulolytic Clostridium papyrosolvens
      produces an efficient cellulolytic extracellular complex named cellulosome that
      hydrolyzes plant cell wall polysaccharides into simple sugars. Its genome harbors
      two long cellulosomal clusters: cip-cel operon encoding major cellulosome
      components (including scaffolding) and xyl-doc gene cluster encoding
      hemicellulases. Compared with works on cip-cel operon, there are much fewer
      studies on xyl-doc mainly due to its rare location in cellulolytic clostridia.
      Sequence analysis of xyl-doc revealed that it harbors a 5' untranslated region
      (5'-UTR) which potentially plays a role in the regulation of downstream gene
      expression. Here, we analyzed the function of 5'-UTR of xyl-doc cluster in C.
      papyrosolvens in vivo via transformation technology developed in this study.
      Results: In this study, we firstly developed an electrotransformation method for
      C. papyrosolvens DSM 2782 before the analysis of 5'-UTR of xyl-doc cluster. In
      the optimized condition, a field with an intensity of 7.5-9.0 kV/cm was applied
      to a cuvette (0.2 cm gap) containing a mixture of plasmid and late cell suspended
      in exponential phase to form a 5 ms pulse in a sucrose-containing buffer.
      Afterwards, the putative promoter and the 5'-UTR of xyl-doc cluster were
      determined by sequence alignment. It is indicated that xyl-doc possesses a long
      conservative 5'-UTR with a complex secondary structure encompassing at least two
      perfect stem-loops which are potential candidates for controlling the
      transcriptional termination. In the last step, we employed an oxygen-independent
      flavin-based fluorescent protein (FbFP) as a quantitative reporter to analyze
      promoter activity and 5'-UTR function in vivo. It revealed that 5'-UTR
      significantly blocked transcription of downstream genes, but corn stover can
      relieve its suppression. Conclusions: In the present study, our results
      demonstrated that 5'-UTR of the cellulosomal xyl-doc cluster blocks the
      transcriptional activity of promoter. However, some substrates, such as corn
      stover, can relieve the effect of depression of 5'-UTR. Thus, it is speculated
      that 5'-UTR of xyl-doc was a putative riboswitch to regulate the expression of
      downstream cellulosomal genes, which is helpful to understand the complex
      regulation of cellulosome.

PMID- 29467820
TI  - Genomic comparison of Clostridium species with the potential of utilizing red
      algal biomass for biobutanol production.
AB  - Background: Sustainable biofuels, which are widely considered as an attractive
      alternative to fossil fuels, can be generated by utilizing various biomass from
      the environment. Marine biomass, such as red algal biomass, is regarded as one
      potential renewable substrate source for biofuels conversion due to its abundance
      of fermentable sugars (e.g., galactose). Previous studies focused on the
      enhancement of biofuels production from different Clostridium species; however,
      there has been limited investigation into their metabolic pathways, especially on
      the conversion of biofuels from galactose, via whole genomic comparison and
      evolutionary analysis. Results: Two galactose-utilizing Clostridial strains were
      examined and identified as Clostridium acetobutylicum strain WA and C.
      beijerinckii strain WB. Via the genomic sequencing of both strains, the
      comparison of the whole genome together with the relevant protein prediction of
      33 other Clostridium species was established to reveal a clear genome profile
      based upon various genomic features. Among them, five representative strains,
      including C. beijerinckii NCIMB14988, C. diolis DSM 15410, C. pasteurianum BC1,
      strain WA and WB, were further discussed to demonstrate the main differences
      among their respective metabolic pathways, especially in their carbohydrate
      metabolism. The metabolic pathways involved in the generation of biofuels and
      other potential products (e.g., riboflavin) were also reconstructed based on the
      utilization of marine biomass. Finally, a batch fermentation process was
      performed to verify the fermentative products from strains WA and WB using 60 g/L
      of galactose, which is the main hydrolysate from algal biomass. It was observed
      that strain WA and WB could produce up to 16.98 and 12.47 g/L of biobutanol,
      together with 21,560 and 10,140 mL/L biohydrogen, respectively. Conclusions: The
      determination of the production of various biofuels by both strains WA and WB and
      their genomic comparisons with other typical Clostridium species on the analysis
      of various metabolic pathways was presented. Through the identification of their
      metabolic pathways, which are involved in the conversion of galactose into
      various potential products, such as biobutanol, the obtained results extend the
      current insight into the potential capability of utilizing marine red algal
      biomass and provide a systematic investigation into the relationship between this
      genus and the generation of sustainable bioenergy.

PMID- 29467822
TI  - Tension wood structure and morphology conducive for better enzymatic digestion.
AB  - Background: Tension wood is a type of reaction wood in response to bending or
      leaning stem as a corrective growth process. Tension wood is formed by both
      natural and man-made processes. Most attractively, tension wood contains higher
      glucan content and undergoes higher enzymatic conversion to fermentable sugars.
      Here, we have employed structural techniques, small-angle neutron scattering
      (SANS) and wide-angle X-ray diffraction (WAXD) to elucidate structural and
      morphological aspects of tension wood conducive to higher sugar yields. Results:
      Small-angle neutron scattering data exhibited a tri-modal distribution of the
      fibril cross-sectional dimension. The smallest size, 22 A observed in all samples
      concurred with the WAXD results of the control and opposite side samples. This
      smallest and the most abundant occurring size was interpreted as the cellulose
      elementary microfibril diameter. The intermediate size of 45 A, which is most
      pronounced in the tension side sample and consistent with WAXD results for
      tension side sample, indicates association of neighboring elementary microfibrils
      to form larger crystallite bundles. The largest size 61 A observed by SANS was
      however not observed by WAXD and therefore associated to mesopores. Conclusions:
      Structure and morphology of tension wood is different from control wood.
      Cellulose crystallinity increases, lignin content is lower and the appearance of
      mesopores with 61 A diameter is observed. Despite the presence of higher
      crystalline cellulose content in tension side, the lower lignin content and may
      be combined with the abundance of mesopores, substantially improves enzyme
      accessibility leading to higher yields in cellulose digestion.

PMID- 29467824
TI  - Familial intellectual disability as a result of a derivative chromosome 22
      originating from a balanced translocation (3;22) in a four generation family.
AB  - Background: Balanced reciprocal translocation is usually an exchange of two
      terminal segments from different chromosomes without phenotypic effect on the
      carrier while leading to increased risk of generating unbalanced gametes. Here we
      describe a four-generation family in Shandong province of China with at least
      three patients sharing severe intellectual disability and developmental delay
      resulting from a derivative chromosome 22 originating from a balanced
      translocation (3;22) involving chromosomes 3q28q29 and 22q13.3. Methods: The
      proband and his relatives were detected by using karyotyping, chromosome
      microarray analysis, fluorescent in situ hybridization and real-time qPCR.
      Results: The proband, a 17 month-old boy, presented with severe intellectual
      disability, developmental delay, specific facial features and special posture of
      hands. Pedigree analysis showed that there were at least three affected patients.
      The proband and other two living patients manifested similar phenotypes and were
      identified to have identically abnormal cytogenetic result with an unbalanced
      translocation of 9.0 Mb duplication at 3q28q29 and a 1.7Mb microdeletion at
      22q13.3 by karyotyping and chromosome microarray analysis. His father and other
      five relatives had a balanced translocation of 3q and 22q. Fluorescence in situ
      hybridization and real-time qPCR definitely validated the results. Conclusions:
      The abnormal phenotypes of the proband and his two living members in four
      generations of the family confirmed the 3q duplication and 22q13.3 deletion
      inherited from familial balanced translocation. This is the first report of
      familial balanced reciprocal translocation involving chromosomes 3q28q29 and
      22q13.3 segregating through four generations.

PMID- 29467823
TI  - In vitro and in vivo characterization of three Cellvibrio japonicus glycoside
      hydrolase family 5 members reveals potent xyloglucan backbone-cleaving functions.
AB  - Background: Xyloglucan (XyG) is a ubiquitous and fundamental polysaccharide of
      plant cell walls. Due to its structural complexity, XyG requires a combination of
      backbone-cleaving and sidechain-debranching enzymes for complete deconstruction
      into its component monosaccharides. The soil saprophyte Cellvibrio japonicus has
      emerged as a genetically tractable model system to study biomass
      saccharification, in part due to its innate capacity to utilize a wide range of
      plant polysaccharides for growth. Whereas the downstream debranching enzymes of
      the xyloglucan utilization system of C. japonicus have been functionally
      characterized, the requisite backbone-cleaving endo-xyloglucanases were
      unresolved. Results: Combined bioinformatic and transcriptomic analyses
      implicated three glycoside hydrolase family 5 subfamily 4 (GH5_4) members, with
      distinct modular organization, as potential keystone endo-xyloglucanases in C.
      japonicus. Detailed biochemical and enzymatic characterization of the GH5_4
      modules of all three recombinant proteins confirmed particularly high
      specificities for the XyG polysaccharide versus a panel of other cell wall
      glycans, including mixed-linkage beta-glucan and cellulose. Moreover, product
      analysis demonstrated that all three enzymes generated XyG oligosaccharides
      required for subsequent saccharification by known exo-glycosidases.
      Crystallographic analysis of GH5D, which was the only GH5_4 member specifically
      and highly upregulated during growth on XyG, in free, product-complex, and active
      site affinity-labelled forms revealed the molecular basis for the exquisite XyG
      specificity among these GH5_4 enzymes. Strikingly, exhaustive reverse-genetic
      analysis of all three GH5_4 members and a previously biochemically characterized
      GH74 member failed to reveal a growth defect, thereby indicating functional
      compensation in vivo, both among members of this cohort and by other, yet
      unidentified, xyloglucanases in C. japonicus. Our systems-based analysis
      indicates distinct substrate-sensing (GH74, GH5E, GH5F) and attack-mounting
      (GH5D) functions for the endo-xyloglucanases characterized here. Conclusions:
      Through a multi-faceted, molecular systems-based approach, this study provides a
      new insight into the saccharification pathway of xyloglucan utilization system of
      C. japonicus. The detailed structural-functional characterization of three
      distinct GH5_4 endo-xyloglucanases will inform future bioinformatic predictions
      across species, and provides new CAZymes with defined specificity that may be
      harnessed in industrial and other biotechnological applications.

PMID- 29467825
TI  - Investigating the parameter space of evolutionary algorithms.
AB  - Evolutionary computation (EC) has been widely applied to biological and
      biomedical data. The practice of EC involves the tuning of many parameters, such
      as population size, generation count, selection size, and crossover and mutation
      rates. Through an extensive series of experiments over multiple evolutionary
      algorithm implementations and 25 problems we show that parameter space tends to
      be rife with viable parameters, at least for the problems studied herein. We
      discuss the implications of this finding in practice for the researcher employing
      EC.

PMID- 29467826
TI  - A novel joint analysis framework improves identification of differentially
      expressed genes in cross disease transcriptomic analysis.
AB  - Motivation: Detecting differentially expressed (DE) genes between disease and
      normal control group is one of the most common analyses in genome-wide
      transcriptomic data. Since most studies don't have a lot of samples, researchers
      have used meta-analysis to group different datasets for the same disease. Even
      then, in many cases the statistical power is still not enough. Taking into
      account the fact that many diseases share the same disease genes, it is desirable
      to design a statistical framework that can identify diseases' common and specific
      DE genes simultaneously to improve the identification power. Results: We
      developed a novel empirical Bayes based mixture model to identify DE genes in
      specific study by leveraging the shared information across multiple different
      disease expression data sets. The effectiveness of joint analysis was
      demonstrated through comprehensive simulation studies and two real data
      applications. The simulation results showed that our method consistently
      outperformed single data set analysis and two other meta-analysis methods in
      identification power. In real data analysis, overall our method demonstrated
      better identification power in detecting DE genes and prioritized more disease
      related genes and disease related pathways than single data set analysis. Over
      150% more disease related genes are identified by our method in application to
      Huntington's disease. We expect that our method would provide researchers a new
      way of utilizing available data sets from different diseases when sample size of
      the focused disease is limited.

PMID- 29467827
TI  - Advanced imaging techniques for small bowel Crohn's disease: what does the future
      hold?
AB  - Treatment of Crohn's disease (CD) is intrinsically reliant on imaging techniques,
      due to the preponderance of small bowel disease and its transmural pattern of
      inflammation. Ultrasound (US), computed tomography (CT) and magnetic resonance
      imaging (MRI) are the most widely employed imaging methods and have excellent
      diagnostic accuracy in most instances. Some limitations persist, perhaps the most
      clinically relevant being the distinction between inflammatory and fibrotic
      strictures. In this regard, several methodologies have recently been tested in
      animal models and human patients, namely US strain elastography, shear wave
      elastography, contrast-enhanced US, magnetization transfer MRI and contrast
      dynamics in standard MRI. Technical advances in each of the imaging methods may
      expand their indications. The addition of oral contrast to abdominal US appears
      to substantially improve its diagnostic capabilities compared to standard US.
      Ionizing dose-reduction methods in CT can decrease concern about cumulative
      radiation exposure in CD patients and diffusion-weighted MRI may reduce the need
      for gadolinium contrast. Clinical indexes of disease activity and severity are
      also increasingly relying on imaging scores, such as the recently developed
      Lemann Index. In this review we summarize some of the recent advances in small
      bowel CD imaging and how they might affect clinical practice in the near future.

PMID- 29467828
TI  - Age-related differences in foot mobility in individuals with patellofemoral pain.
AB  - Background: Age-related changes in midfoot mobility have the potential to
      influence success with foot orthoses intervention in people with patellofemoral
      pain (PFP). The aim of this study was to determine whether older people with PFP
      demonstrate less foot mobility than younger adults with PFP. Methods: One hundred
      ninety four participants (113 (58%) women, age 32 +/- 7 years, BMI 25 +/- 4.9
      kg/m2) with PFP (>= 6 weeks duration) were included, with foot mobility
      quantified using reliable and valid methods. K-means cluster analysis classified
      participants into three homogenous groups based on age. After cluster formation,
      univariate analyses of co-variance (covariates: sex, weight) were used to compare
      midfoot height mobility, midfoot width mobility, and foot mobility magnitude
      between age groups (significance level 0.05). Results: Cluster analysis revealed
      three distinct age groups: 18-29 years (n = 70); 30-39 years (n = 101); and 40-50
      years (n = 23). There was a significant main effect for age for midfoot height
      mobility (p < 0.001) and foot mobility magnitude (p = 0.006). Post-hoc analyses
      revealed that midfoot height mobility differed across all three groups (moderate
      to large effect sizes), and that foot mobility magnitude was significantly less
      in those aged 40-50 years compared to those aged 18-25 years (moderate effect
      size). There were no significant main effects for age for midfoot width mobility
      (p > 0.05). Conclusion: Individuals with PFP aged 40-50 years have less foot
      mobility than younger adults with PFP. These findings may have implications for
      evaluation and treatment of older individuals with PFP.

PMID- 29467829
TI  - Surgical offloading procedures for diabetic foot ulcers compared to best non
      surgical treatment: a study protocol for a randomized controlled trial.
AB  - Background: Diabetic foot ulcers are frequently related to elevated pressure
      under a bony prominence. Conservative treatment includes offloading with
      orthopaedic shoes and custom made orthotics or plaster casts. While casting in
      plaster is usually effective in achieving primary closure of foot ulcers,
      recurrence rates are high. Minimally invasive surgical offloading that includes
      correction of foot deformities has good short and long term results. The surgery
      alleviates the pressure under the bony prominence, thus enabling prompt ulcer
      healing, negating the patient's dependence on expensive shoes and orthotics, with
      a lower chance of recurrence. The purpose of this protocol is to compare
      offloading surgery (percutaneous flexor tenotomy, mini-invasive floating
      metatarsal osteotomy or Keller arthroplasty) to non-surgical treatment for
      patients with diabetic foot ulcers in a semi-crossover designed RCT. Methods: One
      hundred patients with diabetic neuropathy related foot ulcers (tip of toe ulcers,
      ulcers under metatarsal heads and ulcers under the hallux interphalangeal joint)
      will be randomized (2:3) to a surgical offloading procedure or best available non
      surgical treatment. Group 1 (surgery) will have surgery within 1 week. Group 2
      (controls) will be prescribed an offloading cast applied for up to 12 weeks
      (based on clinical considerations). Following successful offloading treatment
      (ulcer closure with complete epithelization) patients will be prescribed
      orthopaedic shoes and custom made orthotics. If offloading by cast for at least 6
      weeks fails, or the ulcer recurs, patients will be offered surgical offloading.
      Follow-up will take place till 2 years following randomization. Outcome criteria
      will be time to healing of the primary ulcer (complete epithelization), time to
      healing of surgical wound, recurrence of ulcer, time to recurrence and
      complications. Discussion: The high recurrence rate of foot ulcers and their dire
      consequences justify attempts to find better solutions than the non-surgical
      options available at present. To promote surgery, RCT level evidence of efficacy
      is necessary. Trial registration: Israel MOH_2017-08-10_000719. NIH: NCT03414216.

PMID- 29467830
TI  - Risk perception of cardiovascular diseases among individuals with hypertension in
      rural Malaysia.
AB  - Objective: Despite various efforts, hypertension remains poorly controlled, thus
      allowing cardiovascular disease (CVD) to impact the health burden worldwide.
      Patients' perception of risk may contribute to this scenario. The present study
      aims to assess the level of risk perception among individuals with hypertension
      in rural Malaysia. Methods: This is a community-based study conducted among
      adults between 2010 and 2011 among a rural population in Raub, Pahang, Malaysia.
      Blood pressure was measured after 5 min of rest. Measurement was done twice and
      the average was recorded. Cardiovascular risk perception score (CvRPS) was
      derived using the Modified Risk and Health Behavior Questionnaire. Higher CvRPS
      indicates the respondent perceives a poorer prognostic outlook. Results: A total
      of 383 respondents who have hypertension participated in this study. The mean age
      of respondents was 62+/-10.6 years; men 63.1+/-9.6 years, women 61.2+/-11.1 years
      (p>0.05). Among hypertensives, those who were not on medication had significantly
      lower CvRPS compared with those who were on medications (115.9+/-22.1vs 120.9+/
      23.5, p=0.036); those who were not aware of their hypertensive status had
      significantly lower CvRPS compared with respondents who were aware about their
      hypertension (116.7+/-22.5vs 121.7+/-21.3, p=0.029) and those with uncontrolled
      hypertension had significantly lower CvRPS compared with those whose blood
      pressure was controlled (118.2+/-22.2vs 128.8+/-25.8, p=0.009). Conclusions: Our
      study shows that respondents who were not on medications, unaware of their
      hypertension status and those who had uncontrolled hypertension tended to
      underestimate (lower CvRPS) their risk for CVD. Improving their CvPRS through a
      concerted health education may lead to better therapeutic behaviour and outcomes.

PMID- 29467831
TI  - Non-compaction of left ventricular myocardium in sub-Saharan African adults.
AB  - Background: Non-compaction of the left ventricle (NCLV) is an unclassified
      cardiomyopathy due to intrauterine arrest of compaction of the loose interwoven
      meshwork. Only a few studies involving sub-Saharan Africans insmall numbers have
      been published. The aim of our study was to determine the diagnostic, therapeutic
      and prognostic aspects as well as the clinical course of NCLV in a black African
      population. Methodology: A multicentre retrospective study was carried out
      between November 2007 and June 2012 in two cardiology departments in Dakar.
      Patients who met the echocardiographic criteria for NCLV were included in the
      study. Results: 35patients with the diagnosis of NCLV were evaluated in the
      study. Their mean age was 47+/-18.4 years. Heart failure was found in 77.1% of
      the patients. The most frequent electrocardiographic abnormalities were left
      ventricular hypertrophy (LVH) (46%) and sinus tachycardia (43%). Mean non
      compaction/compaction ratio was 2.84+/-0.68 with preferential localization in the
      apex of the left ventricle. The main complications observed were cardiogenic
      shock (23.5%), pulmonary embolism (6.3%) and ventricular tachycardia (5.9%).
      Diuretics and ACE inhibitors were the medications most often prescribed. Age >60
      years (p=0.04), male gender (p=0.03) and the occurrence of complications during
      follow-up (p=0.04) were noted to be predictors of poor prognosis. Conclusion:
      Contrary to previous beliefs, NCLV may not be less common in black Africans than
      in other ethnic subgroups. Clinicians in Africa should be made aware of NCLV so
      that it can be diagnosed at earlier stages.

PMID- 29467832
TI  - Implications of prescribing a fixed-dose combination in clinical cardiology
      practice: a retrospective observational study using a single medical centre
      database in Korea.
AB  - Objective: Fixed-dose combination (FDC) prescribing enhances adherence to
      medication. However, there are limited data regarding the usefulness of FDC drugs
      across different risk groups. The aim of this study was to explore the
      relationship between FDC discontinuation and clinical outcomes. Methods: From
      January 2008 to December 2014, patients with FDC prescriptions who visited a
      cardiology outpatient clinic at a tertiary university hospital in Daegu, Republic
      of Korea were retrospectively identified. The 10-year atherosclerotic
      cardiovascular disease (ASCVD) risk score and 20 conventional cardiovascular (CV)
      risk factors were assessed. Patients were classified according to FDC
      continuation, together with a tertile of 20 risks. CV events were defined as the
      composite of admission for worsening heart failure or diabetes, stroke, ischaemic
      heart disease, and CV death. Results: 502 patients were prescribed with one of
      the following FDC products: calcium channel blocker (CCB) plus angiotensin
      receptor blockers (ARB), CCB plus statins, and ARB plus diuretics. During follow
      up (mean 2.8+/-2.4 years), 203 discontinuations (40.4%) occurred. FDC
      discontinued patients had lower ASCVD risk scores (24.8% vs. 28.8%, p<0.001), and
      patients with <6 risk factors discontinued FDC frequently. During follow-up, 57
      events (11.4%) were reported: 30 (14.8%) in FDC-discontinued patients and 27
      (9.1%) in FDC-continued patients (p=0.062). In multivariate models accounting for
      events, FDC discontinuation (p<0.001) and high ASCVD risk score (p=0.017) were
      associated with CV events. Conclusions: FDC discontinuation was common among
      patients attending the cardiology outpatient clinic. Our analyses suggest that
      FDC discontinuation in patients at high ASCVD risk may have an impact on CV event
      rates.

PMID- 29467833
TI  - Cardiovascular risk in an HIV-infected population in India.
AB  - Objective: To characterise prevalence of traditional cardiovascular disease (CVD)
      risk factors, assess CVD risk and examine the effect of simulated interventions
      on CVD risk among HIV-infected Asian Indians. Methods: Cross-sectional data
      between September 2015 and July 2016 wer used to describe the prevalence of CVD
      risk factors. Five risk scores (Framingham, Data Collection on Adverse Effects of
      Anti-HIV Drugs Study (D:A:D), Atherosclerotic Cardiovascular, QRISK2 and
      Ramathibodi-Electricity Generating Authority of Thailand were used to estimate
      CVD risk. The effect of seven sensitivity analyses: smoking prevention; diabetes
      prevention; optimal blood pressure and dyslipidaemia control (total cholesterol,
      high-density lipoprotein (HDL)); CD4 augmentation and a combination of the
      scenarios on the median cumulative D:A:D CVD scores were assessed. Results: Of
      402 enrolled, 56% were women, median age was 40 years (IQR: 35-45 years) and
      median time-updated CD4 counts were 378 cells/MUL (IQR: 246-622). Fifty-five and
      28% had ever been screened for hypertension and diabetes, respectively prior to
      enrolment. The prevalence of diabetes, hypertension, hypercholesterolaemia, low
      HDL, previous and current smokers were 9%, 22%, 20%, 39%, 14% and 4%,
      respectively. Thirty-six per cent had intermediate-to-high 5-year CVD risk by
      D:A:D estimates. Thirty-two per cent were eligible for statin therapy by American
      College of Cardiology/American Heart Association guidelines; 2% were currently on
      statins. In sensitivity analyses, diabetes prevention was associated with the
      highest reduction of CVD risk. Conclusion: CVD at younger ages among Asian Indian
      people living with HIV appear to be an imminent risk for morbidity. Stepping up
      of preventive services including screening services and prescription of statins
      are important strategies that must be considered.

PMID- 29467834
TI  - Rheumatic heart disease with a mitral blood cyst: three-dimensional
      echocardiographic imaging.

PMID- 29467835
TI  - Development of local clinical practice guidelines in the real world: an evolving
      scene in China.

PMID- 29467836
TI  - An evaluation of the 25 by 25 goal for premature cardiovascular disease mortality
      in Taiwan: an age-period-cohort analysis, population attributable fraction and
      national population-based study.
AB  - Objectives: The aim of the 25 by 25 goal is to reduce mortality from premature
      non-communicable diseases by 25% before 2025. Studies have evaluated the 25 by 25
      goal in many countries, but not in Taiwan. The aim of this study was to estimate
      the 25 by 25 goal for premature mortality from cardiovascular diseases in Taiwan.
      Methods: We applied the age-period-cohort model to project the incidence of
      premature death from cardiovascular disease from 2015 to 2024 and used the
      population attributable fraction to estimate the contributions of targeted risk
      factors. The probability of death was used to estimate the percent change.
      Results: The percent change in business-as-usual trend during 2010-2024 was only
      a 6% (range 1.7-10.7%) lower risk of premature mortality from cardiovascular
      disease among men. The greatest reduction in the risk of mortality occurred with
      a 30% reduction in the prevalence of smoking; however, there was only a 14.5%
      (10.6-18.3%) decrease in percent change and in the corresponding number of men
      (3706: range 3543-3868) who were prevented from dying. More than a 25% reduction
      in the percent change of premature cardiovascular disease mortality among women
      was achieved without control of any risk factor. To reach a 25% reduction in men
      before 2025, there needs to be a 70% reduction in the prevalence of smoking to
      reduce mortality by 26.2% (22.9-29.3%). Conclusions: Cigarette smoking is the
      primary target in the prevention of cardiovascular disease. Through the stringent
      control of smoking, the goal of a 25% reduction in premature mortality from
      cardiovascular disease may be achieved before 2025 in Taiwan.

PMID- 29467837
TI  - Is white rice consumption a risk for metabolic and cardiovascular outcomes? A
      systematic review and meta-analysis.
AB  - Objective: The main objective of this systematic review and meta-analysis was to
      investigate the association between white rice consumption and risk of metabolic
      and cardiovascular outcomes. Methods: We conducted a comprehensive search of
      Medline, Embase, Scopus, and the Cochrane Central Register of Controlled Trials
      from database inception through March 2016. Original studies that reported
      associations between white rice consumption and cardiovascular outcomes
      regardless of study design were selected. We extracted study characteristics and
      outcome data. Conflicts were resolved through consensus. Using the DerSimonian
      and Laird random effects models, we calculated pooled relative risks with 95% CI.
      Results: Our search identified 721 citations. 18 studies were included with a
      total of 1 777 059 individuals: 14 348 had type 2 diabetes mellitus (T2DM); 5612
      had metabolic syndrome (MetS); 10 839 had coronary heart disease (CHD); and 11
      698 had stroke. Compared with the lowest category, the highest category of white
      rice consumption was only associated with 30% higher risk of MetS (pooled OR
      1.30, 95% CI 1.03 to 1.65; p<0.001; I2=65.5%). Conclusions: Higher white rice
      consumption has not been shown to be associated with increased risk of CHD,
      stroke and T2DM. However, white rice consumption may be associated with increased
      risk of MetS in certain populations.

PMID- 29467838
TI  - Pulmonary and right ventricular dysfunction are frequently present in heart
      failure irrespective of left ventricular ejection fraction.
AB  - Background: Heart failure (HF) may influence the lungs and vice versa. However,
      this interaction and the influence on right ventricular function (RVF) are
      insufficiently described in patients with HF divided into the recent groups based
      on left ventricular ejection fraction (LVEF): HF with reduced, midrange and
      preserved ejection fraction (HFrEF, HFmrEF and HFpEF, respectively). Methods:
      Overall, 186 consecutive stable patients with HF seen in our outpatient clinic
      were retrospectively divided into HFrEF (n=70), HFmrEF (n=55) and HFpEF (n=61).
      Airflow limitation and gas exchange disturbance were measured by spirometry
      (forced expiratory volume in the first second/forced vital capacity (FEV1/FVC)
      (%)) and diffusion capacity of the lungs for carbon monoxide (DLCO). Standard
      echocardiography was performed to measure RV structure (RV diameter) and function
      (tricuspid annular plane systolic excursion/pulmonary artery systolic pressure
      (TAPSE/PASP)). Correlations were used to assess possible relations between
      pulmonary dysfunction and measurements of the RV. Results: None of the
      investigated parameters differed significantly between the three groups (all
      p>0.1); FEV1/FVC was 70%+/-12%, 70%+/-13% and 74%+/-10% in patients with HFrEF,
      HFmrEF and HFpEF (p=0.12) and DLCO was 5.7+/-1.6, 5.7+/-1.8 and 5.6+/-1.6
      mmol/min/kPa, respectively (p=0.95). RV structure and function did not differ
      either (TAPSE/PASP 0.58, 0.60 and 0.57, respectively (p=0.84)). There was a
      correlation of DLCO with RV function (r=0.34, p<0.001). Conclusion: The
      investigated cardiopulmonary parameters were comparable in the three HF groups.
      Diffusion capacity was impaired in more than half of the stable HF population
      independently of the LVEF and showed a correlation with RV function.

PMID- 29467839
TI  - Outcomes after mitral valve surgery for rheumatic heart disease.
AB  - Objective: To further the understanding of the factors influencing outcome
      following rheumatic heart disease (RHD) related mitral valve surgery, which
      globally remains an important cause of heart disease and a particular problem in
      Indigenous Australians. Methods: The Australian Cardiac Surgery Database was
      utilised to assess outcomes following mitral valve repair and replacement for RHD
      and non-RHD valve disease. The association with aetiology, demographics,
      comorbidities, preoperative status and operative procedure was evaluated.
      Results: Mitral valve repairs and replacements undertaken in Australia were
      analysed from 119 and 1078 RHD surgical procedures and 3279 and 2400 non-RHD
      procedures, respectively. RHD mitral valve repair, compared with replacement,
      resulted in a slightly shorter hospital stay and more reoperation for valve
      dysfunction, but no difference in 30-day survival. In unadjusted survival
      analysis to 5 years, RHD mitral valve repair and replacement were no different
      (HR 0.86, 95% CI 0.4 to 1.7), non-RHD repair was superior to replacement (HR 1.7,
      95% CI 1.4 to 2.0), RHD and non-RHD repair were no different (HR 0.9, 95% CI 0.5
      to 1.7), and RHD replacement was superior to non-RHD (HR 1.5, 95% CI 1.2 to 1.9).
      None of these differences persisted in adjusted analyses and there was no
      difference in long-term survival for Indigenous Australians. Conclusion: In this
      large prospective cohort study we have demonstrated that adjusted long-term
      survival following RHD mitral valve repair surgery in Australia is no different
      to replacement and no different to non-RHD. Interpretation of valve surgery
      outcome requires careful consideration of patient factors that may also influence
      survival.

PMID- 29467840
TI  - Prevalence of randomised controlled trials in Japanese cardiovascular journals: a
      descriptive study.
AB  - Background: Little is known about the recent proportion and trends of randomised
      controlled trials (RCTs) published in Japanese cardiovascular journals. Methods
      and results: This study retrospectively reviewed all original research articles
      published between 2006 and 2015 in six English-language journals issued by
      societies related to cardiovascular medicine in Japan. All these journals had
      been indexed in PubMed for more than 5 years until 2015. We examined the 2-year
      trends in the prevalence of RCTs, as well as the types of study subjects and
      interventions investigated. In addition, we applied a multivariable logistic
      regression analysis to assess the factors related to the publication of RCTs. A
      total of 7117 articles were eligible for our analyses. The proportion of RCTs
      among Japanese journals was 3.5% (252/7117). No significant change in the
      prevalence of RCTs among all included journals was noted (3.8% vs 3.1%, p=0.751).
      RCTs related to ischaemic heart disease were the most frequently published
      (85/252, 33.7%). In the multivariable analysis, a male first author (adjusted OR
      (AOR) 1.97; 95% CI 1.30 to 2.99) and reports from Asia (AOR 1.62; 95% CI 1.19 to
      2.21) were significantly associated with the publication of RCTs. Conclusions: In
      Japanese cardiovascular journals, RCTs accounted for 3.5% of all original
      research articles published, and there was no change in the prevalence of RCTs
      during the study period.

PMID- 29467841
TI  - Hepatoprotective effect of methyl ferulic acid against carbon tetrachloride
      induced acute liver injury in rats.
AB  - The present study aimed to investigate the hepatoprotective effects of methyl
      ferulic acid (MFA) against oxidative stress and apoptosis in acute liver injury
      induced by carbon tetrachloride (CCl4) in rats, as well as the underlying
      mechanisms. Sprague Dawley rats were treated with CCl4 after oral administration
      of MFA (25, 50, and 100 mg/kg) or dimethyl diphenyl bicarboxylate (200 mg/kg) for
      7 days. The hepatoprotective effects of MFA were determined by analyzing serum
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as
      well as changes of oxidant parameters. Histopathological analysis was performed
      to determine the degree of hepatic injury. The mechanisms were investigated by
      detecting the levels of NADPH oxidase (NOX) trans-membrane subunit NOX4, its
      ligand p22phox, as well as caspase3, cleaved caspase3, B-cell lymphoma (Bcl)-2,
      Bcl-2-associated X protein (Bax), tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-1, reactive oxygen species (ROS), thiobarbituric acid-reactive substances
      (TBARS), total anti-oxidant capacity (TAC), phosphorylated J-Jun N-terminal
      kinase (p-JNK) and p-p38 mitogen-activated protein kinase (MAPK) using semi
      quantitative polymerase chain reaction, western blot analysis and colorimetric
      assays. MFA treatment significantly decreased serum enzymatic activities of ALT
      and AST. MFA markedly increased activities of liver superoxide dismutase,
      catalase and glutathione peroxidase, and reduced the malondialdehyde
      concentration. Histopathological examination demonstrated that MFA reduced lipid
      degeneration, cytoplasmic vacuolization, necrosis and inflammatory cell
      infiltration in the liversof CCl4-treated rats. MFA treatment markedly inhibited
      the expression of inflammatory factors TNF-alpha and IL-1beta. Mechanistic study
      revealed that MFA decreased the TAC and the levels of ROS and TBARS. Furthermore,
      MFA treatment led to a reduction of the mRNA and protein expression of NOX4 and
      p22phox, as well as the protein levels of caspase3, cleaved caspase-3 and Bax,
      and an upregulation of p-JNK, p-p38 MAPK and Bcl-2 proteins in the liver. The
      present study demonstrated that MFA has hepatoprotective effects against CCl4
      induced acute liver damage. MFA has anti-oxidant, anti-inflammatory and anti
      apoptotic activities and was able to modulate the NOX4/p22phox/ROS-JNK/p38 MAPK
      signaling pathway.

PMID- 29467842
TI  - Hypoxia-inducible factor-1alpha regulates epithelial-to-mesenchymal transition in
      paraquat-induced pulmonary fibrosis by activating lysyl oxidase.
AB  - Pulmonary fibrosis (PF) is one of the most prevalent causes of death following
      paraquat (PQ) poisoning. As demonstrated in previous studies by the present
      authors, epithelial-to-mesenchymal transition (EMT) is associated with PQ-induced
      PF. In addition, hypoxia-inducible factor-1alpha (HIF-1alpha) and lysyl oxidase
      (LOX) promote EMT following PQ poisoning. However, the association between HIF
      1alpha- and LOX-mediated regulation of EMT remains unclear. The present study
      investigated the association between HIF-1alpha and LOX with regard to PQ-induced
      EMT. A549 and RLE-6TN cells were treated with PQ, and HIF-1alpha and LOX
      expression was silenced with short interfering RNAs. Changes in the expression of
      HIF-1alpha, LOX, beta-catenin and EMT-related makers were detected using real
      time quantitative polymerase chain reaction, immunofluorescence, and western
      blotting. HIF-1alpha and LOX were associated with PQ-induced EMT, and their
      expression levels were significantly increased (P<0.05). LOX expression was
      significantly decreased following PQ poisoning when HIF-1alpha expression was
      inhibited (P<0.05). However, the level of HIF-1alpha did not change significantly
      when LOX was silenced. The expression level of beta-catenin and the degree of EMT
      were significantly decreased following HIF-1alpha and LOX silencing in both cell
      lines (P<0.05). The association between HIF-1alpha and LOX in regulating EMT
      during PQ-induced PF may be unidirectional. HIF-1alpha may regulate PQ-induced
      EMT through the LOX/beta-catenin pathway.

PMID- 29467843
TI  - Sirtuin 7 promotes colorectal carcinoma proliferation and invasion through the
      inhibition of E-cadherin.
AB  - Sirtuin 7 (Sirt7) is a member of the sirtuin protein family and is implicated in
      various carcinomas; however, the function of Sirt7 in colorectal carcinoma (CRC)
      remains unclear. The present study aimed to explore the biological function of
      Sirt7 in CRC tissues and cell lines, and to investigate the potential underlying
      mechanism by performing reverse transcription-quantitative polymerase chain
      reaction analyses, western blot analyses, luciferase reporter assays, cell
      proliferation and invasion assays. It was demonstrated that Sirt7 presented a
      higher expression in CRC tissues and cell lines compared with that in normal
      tissues and cells, and this higher expression was correlated with the tumor size,
      the tumor, node and metastasis stage and distant metastasis. Knockdown of Sirt7
      repressed the proliferation ability of SW620 and HCT116 cells in vitro, while
      ectopic expression of Sirt7 increased the epithelial-mesenchymal transition and
      invasion in HT29 and SW480 cells. Notably, these functional effects of Sirt7 were
      exerted through the repression of E-cadherin. Thus, the data of the present study
      indicated a novel mechanistic role for Sirt7 as an oncogene in CRC malignancy,
      and Sirt7 may be a potential therapeutic target.

PMID- 29467844
TI  - Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the
      nuclear factor-kappaB signaling pathway.
AB  - Osteosarcoma is the most common cause of cancer-associated mortality and the
      prognosis is yet to be fully elucidated due to the paucity of effective
      therapeutic targets that significantly influence the quality of life and mean
      survival rates of patients with osteosarcoma. Studies have showed that tripartite
      motif-containing (TRIM)-14 is a member of the TRIM protein family that has a
      vital role in tumor progression and metastasis and promotes angiogenesis,
      invasion and apoptotic resistance of bone cancer. In this study, a chimeric
      antibody targeting TRIM-14 (Chanti-TRIM) was constructed and the molecular
      mechanism of target therapy for TRIM-14 was investigated in osteosarcoma cells
      and xenograft mice. The growth, migration and invasion properties of U-2OS cells
      were analyzed following incubation with 10-160 mg/ml Chanti-TRIM. Apoptosis of U
      2OS cells was detected after Chanti-TRIM treatment. Matrix metalloproteinase
      (MMP)-9-mediated nuclear factor-kappaB (NF-kappaB) signal pathway was analyzed in
      U-2OS cells treated with Chanti-TRIM. The inhibitory efficacy of Chanti-TRIM was
      studied in U-2OS-bearing xenograft mice. Our results demonstrated that
      neutralizing TRIM-14 expression markedly inhibited the growth, migration and
      invasion of osteosarcoma cells, in vitro and in vivo. We found that TRIM-14
      depletion decreased cell viability and induced cells apoptosis in vitro. In
      addition, we identified Chanti-TRIM inhibited growth and promoted apoptosis
      induced by cisplatin through MMP-9-mediated NF-kappaB signal pathway.
      Furthermore, we observed that Chanti-TRIM treatment inhibited osteosarcoma growth
      in vivo. Histological analysis indicated that apoptotic bodies were increased and
      NF-kappaB nuclear translocation factors, including Ikkbeta, p65 and IkBalpha,
      were decreased in tumors treated by Chanti-TRIM. In conclusion, these results
      showed that Chanti-TRIM markedly inhibited the progression of osteosarcoma,
      suggesting Chanti-TRIM may be a potential anti-cancer agent that functions via
      the activation of the NF-kappaB pathway for osteosarcoma.

PMID- 29467845
TI  - 14-3-3beta exerts glioma-promoting effects and is associated with malignant
      progression and poor prognosis in patients with glioma.
AB  - Glioma is a type of tumor that affects the central nervous system. It has been
      demonstrated that 14-3-3beta, a protein that is mainly concentrated in the brain,
      serves an important role in tumor regulation. However, the mechanism of action of
      14-3-3beta that underlies the pathogenesis of glioma remains to be elucidated. In
      the present study, 14-3-3beta was silenced by RNA interference in the human
      glioma cell line U373-MG. Following knockdown of 14-3-3beta, the proliferation,
      colony formation, cell cycle progression, migration and invasion of U373-MG cells
      were significantly decreased (P<0.01), whereas cell apoptosis was increased
      (P<0.01). Furthermore, in a tumor xenograft experiment, silencing 14-3-3beta
      significantly inhibited the in vivo tumor growth of U373-MG cells (P<0.01). The
      results demonstrated that 14-3-3beta levels were significantly higher in human
      glioma tissues compared with normal brain tissues (P<0.01) and high 14-3-3beta
      expression was significantly associated with advanced pathological grade (P<0.03)
      and low Karnofsky performance scale (P<0.003). Patients with glioma who had high
      14-3-3beta levels had a significantly shorter survival time compared with those
      with low expression of 14-3-3beta (P=0.031), suggesting that 14-3-3beta may be an
      effective predictor of the prognosis of patients with glioma. The results of the
      present study indicate that 14-3-3beta serves an oncogenic role in glioma,
      suggesting that 14-3-3beta may have potential as a promising therapeutic target
      for glioma.

PMID- 29467846
TI  - Asiatic acid attenuates high-fat diet-induced impaired spermatogenesis.
AB  - Testicular cell apoptosis is associated with impaired spermatogenesis. It has
      been reported that Asiatic acid (AA) may suppress apoptosis. However, little is
      known about the effect of AA on high-fat diet (HFD)-induced impairment of
      spermatogenesis. The aim of the present study was to determine whether AA
      protects against HFD-induced impairment of spermatogenesis. Sprague-Dawley rats
      were randomly divided into three groups: Control group, HFD group and AA (50
      mg/kg) + HFD group. Rats fed an HFD were orally administered with AA (50 mg/kg)
      daily for 12 weeks, and blood samples, testis and epididymis were harvested for
      further analysis. Sex hormones were detected and hematoxylin and eosin staining
      was performed to examine the morphological changes of the testis. Semen samples
      were collected to evaluate sperm quality and apoptosis was determined. The
      results indicate that AA treatment significantly increased testis weight,
      testis/body weight, spermatogonia, Leydig cells and Sertoli cells in the testis
      of obese mice (P<0.05). AA treatment also attenuated HFD-induced histological
      change. AA treatment prevented HFD-induced decrease of sex hormones and the
      quality of semen samples (P<0.05). Furthermore, HFD-induced apoptosis was
      significantly attenuated by AA treatment (P<0.05). In conclusion, the results
      suggest that AA is able to ameliorate HFD-induced impaired spermatogenesis via
      inhibiting apoptosis in Sprague-Dawley rats. AA may have therapeutic value in the
      treatment of obesity-related impairment of spermatogenesis.

PMID- 29467847
TI  - miRNA-223-3p regulates NLRP3 to promote apoptosis and inhibit proliferation of
      hep3B cells.
AB  - Hepatocellular carcinoma (HCC) is a major malignant tumor type with a high
      incidence and mortality. Infection with hepatitis virus is a high-risk factor.
      Previous studies have demonstrated that microRNA (miR)-223 was downregulated in
      HCC tissues. NOD-like receptor family, pyrin domain containing 3 (NLRP3)-is a
      potential target of miR-223 and has a vital role in hepatitis infection. The
      present study was performed to investigate the role of miR-223 in the
      proliferation and apoptosis of HCC cells through regulating NLRP3. A dual
      luciferase reporter assay was performed to confirm the direct interaction between
      miR-223-3p and the 3' untranslated region of NLRP3 mRNA. Hep3B cells were then
      transfected with miR-223 mimics and the proliferation and apoptosis were
      determined by an MTT and a flow cytometric assay, respectively. The expression of
      NLRP3 and caspase-1 was analyzed at the mRNA as well as at the protein level by
      reverse transcription-quantitative polymerase chain reaction and western blot
      analysis, respectively. The secretion of interleukin (IL)-1beta and IL-18 in the
      culture supernatants was measured by ELISA. The dual luciferase assay confirmed
      NLRP3 as a direct target of miR-223. Overexpression of miR-223 in hep3B cells
      significantly suppressed cell proliferation and promoted apoptosis. Furthermore,
      the expression of NLRP3 was downregulated by miR-223 transfection. Certain
      downstream factors of the NLRP3 pathway were also downregulated following
      overexpression of miR-223. Caspase-1 was decreased at the transcriptional level
      and the cleaved caspase-1 was decreased at the protein level. Secretion of IL
      1beta and IL-18 into the culture medium by cells transfected with miR-223 was
      lower than that by the control cells. In conclusion, the tumor suppressor role of
      miR-223 was associated with the regulation of NLRP3 inflammasome components. miR
      223 inhibited HCC cell proliferation and promoted apoptosis by directly targeting
      NLRP3. Downstream production of caspase-1, IL-1beta and IL-18 were also repressed
      by miR-223. These results provided insight into the association between the
      innate immune system and the genesis of HCC.

PMID- 29467848
TI  - Differential microRNA expression in the prefrontal cortex of mouse offspring
      induced by glyphosate exposure during pregnancy and lactation.
AB  - Glyphosate is the active ingredient in numerous herbicide formulations. The role
      of glyphosate in neurotoxicity has been reported in human and animal models.
      However, the detailed mechanism of the role of glyphosate in neuronal development
      remains unknown. Recently, several studies have reported evidence linking
      neurodevelopmental disorders (NDDs) with gestational glyphosate exposure. The
      current group previously identified microRNAs (miRNAs) that are associated with
      the etiology of NDDs, but their expression levels in the developing brain
      following glyphosate exposure have not been characterized. In the present study,
      miRNA expression patterns were evaluated in the prefrontal cortex (PFC) of 28
      postnatal day mouse offspring following glyphosate exposure during pregnancy and
      lactation. An miRNA microarray detected 55 upregulated and 19 downregulated
      miRNAs in the PFC of mouse offspring, and 20 selected deregulated miRNAs were
      further evaluated by quantitative polymerase chain reaction (PCR). A total of 11
      targets of these selected deregulated miRNAs were analyzed using bioinformatics.
      Gene Ontology (GO) terms associated with the relevant miRNAs included
      neurogenesis (GO:0050769), neuron differentiation (GO:0030182) and brain
      development (GO:0007420). The genes Cdkn1a, Numbl, Notch1, Fosl1 and Lef1 are
      involved in the Wnt and Notch signaling pathways, which are closely associated
      with neural development. PCR arrays for the mouse Wnt and Notch signaling
      pathways were used to validate the effects of glyphosate on the expression
      pattern of genes involved in the Wnt and Notch pathways. Nr4a2 and Wnt7b were
      downregulated, while Dkk1, Dixdc1, Runx1, Shh, Lef-1 and Axin2 were upregulated
      in the PFC of mice offspring following glyphosate exposure during pregnancy and
      lactation. These results indicated abnormalities of the Wnt/beta-catenin and
      Notch pathways. These findings may be of particular interest for understanding
      the mechanism of glyphosate-induced neurotoxicity, as well as helping to clarify
      the association between glyphosate and NDDs.

PMID- 29467849
TI  - Efficacy and survival rate of intensity-modulated radiotherapy combined with
      chemotherapy for elderly patients with locally advanced oropharyngeal cancer.
AB  - The efficacy of intensity-modulated radiotherapy (IMRT) combined with
      chemotherapy in the treatment of elderly patients with locally advanced
      oropharyngeal cancer and its effect on survival rate were studied. Elderly
      patients (n=150) diagnosed with locally advanced oropharyngeal cancer by
      histopathology were selected and randomly divided into the observation group
      (n=75) and the control group (n=75). Patients in the observation group were
      treated with IMRT combined with chemotherapy, while those in the control group
      were treated with conventional radiotherapy and chemotherapy. The two groups were
      treated with docetaxel + cisplatin (TP regimen). All patients received 1 to 2
      cycles of docetaxel + cisplatin-induced chemotherapy, and after the radiotherapy
      began, the chemotherapy with docetaxel was synchronously conducted. The recent
      efficacy (tumor regression condition was observed at 3 months after the
      treatment), 1-year, 3-year and 5-year overall survival (OS), local-regional
      control (LRC), progression-free survival (PFS), disease-free survival (DFS) and
      the incidence rate of adverse reactions of patients in the two groups were
      compared. In the observation group, 73 patients completed the radiotherapy and
      chemotherapy, while all the patients in the control group completed the
      treatments. The 1-year OS of the observation group and the control group was 97.3
      and 85.3%, respectively. In the observation group, the 3-year LRC, OS, PFS and
      DFS of the observation group was 94.5, 91.8, 90.4 and 87.7%, respectively; the 5
      year LRC, OS, PFS and DFS was 64.4, 56.2, 56.2 and 54.8%, respectively. In the
      control group, the 3-year LRC, OS, PFS and DFS was 86.7, 73.3, 82.7 and 68.0%,
      respectively; the 5-year LRC, OS, PFS and DFS were 54.7, 45.3, 44.0 and 56.7%,
      respectively. The differences were statistically significant (P<0.05). In the
      observation group, the number of leukocytes was decreased, and the incidence
      rates of acute oropharyngeal mucosa reaction and radiation dermatitis were
      significantly lower than those in the control group. The differences were
      statistically significant (P<0.05). In conclusion, IMRT combined with
      chemotherapy can improve the OS and the 3-year and 5-year LRC, PFS and DFS of
      elderly patients with locally advanced oropharyngeal cancer, reduce toxic and
      side effects, and improve patients' quality of life.

PMID- 29467850
TI  - Decrease of gamma-aminobutyric acid and zinc ions in the islet periportal
      circulation stimulates glucagon secretion during hypoglycemia.
AB  - The present study assessed the effects of gamma-aminobutyric acid (GABA) from
      beta-cells on glucose levels and glucagon secretion, and identified channels via
      which glucagon secretion is initiated. An in vivo experiment was performed
      containing three groups: Intrapancreatic artery infusion of GABA alone, GABA plus
      insulin or insulin alone in rats with diabetes. Rats infused with GABA and
      insulin were also subdivided in groups receiving additional infusion of K+
      channel activator diazoxide (DIA), K+-channel blocker tolbutamide (TLB) and
      calcium channel blocker nifedipine (NIF). In the hypoglycemic state, termination
      of infusion of insulin and insulin plus GABA resulted in signaling to the alpha
      cells to secrete glycogen, while that of GABA alone did not. However,
      intrapancreatic artery infusion of K+-channel activator DIA, K+-channel blocker
      TLB or calcium channel blocker NIF in addition to GABA and insulin had no effect
      on glucagon secretion. In conclusion, if the delivery of insulin or GABA plus
      insulin in rats with hypoglycemia is terminated, beta-cells are stimulated and
      signal the alpha-cells to secrete glucagon. Thus, the detection of a sudden
      decrease in zinc levels by beta-cells as well as a decrease in GABA in the
      periportal circulation induces signaling to alpha-cells to stimulate them to
      secrete glucagon.

PMID- 29467851
TI  - Proteinase 3 expression on the neutrophils of patients with paroxysmal nocturnal
      hemoglobinuria.
AB  - Proteinase 3 (PR3) is released from neutrophils and regulates platelet activity,
      which is associated with cluster of differentiation (CD)177 antigen (NB1), a
      glycosylphosphatidylinositol-linked protein. In the present study, the effect of
      PR3 on thrombosis in paroxysmal nocturnal hemoglobinuria (PNH) and PNH-aplastic
      anemia (AA) syndrome was explored. The expression of PR3 and NB1 on CD59-
      neutrophils was detected by flow cytometry, immunofluorescence (IF), reverse
      transcription-quantitative polymerase chain reaction analysis and western
      blotting. Serum levels of PR3, proteinase-activated receptor 1 (PAR1) and D-Dimer
      were measured using ELISAs. The expression of PR3 and NB1 on the plasma membrane
      of CD59- neutrophils in patients with PNH/PNH-AA was significantly lower compared
      with their expression on CD59+ neutrophils in patients and controls (P=0.001).
      However, no correlation between PR3 and NB1 expression was identified. IF
      staining further demonstrated partially positive PR3 expression on CD59-
      neutrophils. The serum level of PR3 in patients was identified to be
      significantly decreased compared with healthy controls (P<0.0001), and
      significantly negatively correlated with PAR1 (r=-0.456; P=0.043) and D-Dimer (r=
      0.503; P=0.028) levels. The mRNA and protein levels of PR3 on PNH clones did not
      change significantly compared with the control group. In conclusion, PR3
      expression on the plasma membrane of neutrophils and in the serum of patients
      with PNH/PNH-AA decreased, which may result in increased PAR1 expression and
      increased clotting. The present study provides the basis for further study on
      platelets in PNH.

PMID- 29467852
TI  - In vitro and in vivo cytotoxic effect of AntiGan against tumor cells.
AB  - Novel effective chemopreventive agents against cancer are required to improve
      current therapeutic rates. The aim of the present study was to investigate the
      anti-carcinogenesis effect of AntiGan, an extract obtained from the European
      conger eel, Conger conger, in vitro (human tumor cell lines) and in vivo (murine
      model of colitis) models. The potential apoptogenic activity after 24 h of
      incubation with 10, 25 and 50 ul/ml AntiGan was reported using growth inhibition
      and apoptosis activity assays. In vivo studies were performed in mice by inducing
      colitis with oral administration of 2% dextran sulphate sodium (DSS) for 5 weeks.
      Apoptosis was observed in HL-60, Hs 313.T, SW-480, Caco-2 and HT-29 cell lines.
      The highest level of growth inhibition was observed in Caco-2 (66, 75.8 and
      88.1%), HT-29 (56, 73 and 87.6%) and SW-480 (38.5, 61.6, 78.6%) for AntiGan doses
      of 10, 25 and 50 ul/ml, respectively, compared to untreated cells, while the
      results of the expression of genes associated with apoptosis indicated a
      downregulation of B-cell lymphoma 2 (Bcl-2) in all cell lines studied. In vivo,
      morphopathological alterations in the colon were analyzed by immunohistochemical
      and staining methods. Tumoral markers, including beta-catenin, cyclooxygenase 2
      and Bcl-2 were expressed in cryptal cells of the dysplastic colonic mucosa,
      whereas the levels of interferon-gamma expression were also increased when no
      treatment was applied. In the experimental murine model, the optimal
      concentration of AntiGan for an effective dose-response was 10% in diet. These
      results suggested that AntiGan displays a powerful anti-inflammatory effect in
      DSS-induced colitis, acting as a chemopreventive agent against colon
      carcinogenesis, most likely due to its apoptogenic peptides that contribute to
      the induction of apoptosis.

PMID- 29467853
TI  - 640-slice DVCT multi-dimensionally and dynamically presents changes in bladder
      volume and urine flow rate.
AB  - The present study aimed to explore the application of 640-slice dynamic volume
      computed tomography (DVCT) to excretory cystography and urethrography. A total of
      70 healthy subjects were included in the study. Excretory cystography and
      urethrography using 640-slice DVCT was conducted to continuously record the
      motions of the bladder and the proximal female and male urethra. The patients'
      voiding process was divided into early, early to middle, middle, middle to late,
      and late voiding phases. The subjects were analyzed using DVCT and conventional
      CT. The cross-sectional areas of various sections of the male and female urethra
      were evaluated, and the average urine flow rate was calculated. The 640-slice
      DVCT technique was used to dynamically observe the urine flow rate and changes in
      bladder volume at all voiding phases. The urine volume detected by 640-slice DVCT
      exhibited no significant difference compared with the actual volume, and no
      significant difference compared with that determined using conventional CT.
      Furthermore, no significant difference in the volume of the bladder at each phase
      of the voiding process was detected between 640-slice DVCT and conventional CT.
      The results indicate that 640-slice DVCT can accurately evaluate the status of
      the male posterior urethra and female urethra. In conclusion, 640-slice DVCT is
      able to multi-dimensionally and dynamically present changes in bladder volume and
      urine flow rate, and could obtain similar results to conventional CT in detecting
      urine volume, as well as the status of the male posterior urethra and female
      urethra.

PMID- 29467854
TI  - Cholecystokinin octapeptide inhibits the inflammatory response and improves
      neurological outcome in a porcine model of cardiopulmonary resuscitation.
AB  - Previous studies have demonstrated that cholecystokinin octapeptide (CCK8)
      induces hypothermia and inhibits the systemic inflammatory response in septic
      shock in rat and murine models. The present study aimed to ascertain whether CCK8
      induced hypothermia and improved the neurological outcomes in a porcine model of
      cardiopulmonary resuscitation (CPR). Ventricular fibrillation was induced and
      left untreated for 10 min in 12 male Bama miniature pigs. Defibrillation was
      attempted after 5 min of CPR. At 5 min following resuscitation, the pigs were
      randomized and equally assigned into the CCK8 or the control group. CCK8 was
      continuously infused for 1 h at a dose of 44.4 ug/kg/h and a rate of 20 ml/h in
      the CCK8 group. Body temperature, hemodynamic measurements and post-resuscitation
      myocardial function were monitored in the first 4 h following CPR. Neuron
      specific enzyme (NSE), S100B protein, tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-6 were measured at baseline and 4, 12 and 24 h following
      resuscitation. The neurological deficient score (NDS) was recorded and cerebral
      samples were collected for terminal deoxynucleotidyl-transferase-mediated dUTP
      nick end labelling assay and integrated optical density (IOD) analysis at 24 h
      following CPR. The results revealed that hypothermia was not induced by CCK8;
      however, post-resuscitation NSE, S100B, IL-6 and TNF-alpha were significantly
      decreased, and NDS and IOD were significantly improved in the CCK8 group compared
      with the control group (P<0.05). The present study revealed that in a porcine
      model of CPR, CCK8 does not induce hypothermia, but inhibits the inflammatory
      response and significantly improves neurological outcomes.

PMID- 29467855
TI  - Clinical characteristics and value in early reperfusion therapy for new onset
      right bundle branch block in patients with acute myocardial infarction.
AB  - The value of the right bundle branch block (RBBB) in the treatment of acute
      myocardial infarction remains unclear. Studies on the RBBB may significantly
      influence the treatment of acute myocardial infarction. A total of 845 patients
      with acute myocardial infarction who underwent primary coronary angiography at
      Henan Provincial People's Hospital were analyzed. Higher peak enzyme levels, a
      higher ratio of Killip >=II and closer proximal occlusion of infarct-related
      artery (IRA) were observed in patients with RBBB compared with those without. The
      ratio of TIMI flow 0/1 of IRA and ratio of received primary percutaneous coronary
      intervention (PCI) to IRA in the RBBB group were significantly higher compared
      with those in the left (L) BBB or no BBB groups. The in-hospital major adverse
      cardiac events (MACE) incidence in the RBBB group was higher compared with that
      in the no BBB group, but there was no significant difference between the RBBB and
      LBBB groups. Logistic regression revealed that proximal occlusion and TIMI flow
      0/1 of IRA were predictive factors of RBBB. Cox regression analysis identified
      RBBB [risk ratio (RR), 4.682; P<0.001] and LBBB (RR, 3.687; P<0.001) as
      independent predictors of in-hospital MACE. The cumulative one-year survival rate
      in the RBBB group was significantly lower than those in the no BBB group (P<0.05)
      and the LBBB group (P<0.05). Similar to the guidelines regarding new onset of
      LBBB, new onset RBBB should be considered as a standard indicator for reperfusion
      therapy; as RBBB is associated with more severe symptoms, and higher incidents of
      complete occlusion of IRA and primary PCI treatment compared with LBBB.

PMID- 29467856
TI  - Smoking and female sex as key risk factors associated with severe arthralgia in
      acute and chronic phases of Chikungunya virus infection.
AB  - Arthralgia is a potentially incapacitating condition and a persistent symptom in
      chronic or acute episodes of Chikungunya fever caused by infection with the
      Chikungunya virus (CHIKV). To the best of our knowledge, there are no reports on
      risk factors associated with the intensity of arthralgias in typical acute
      episodes of the disease. Although a number of studies have reported on risk
      factors associated with the development of the chronic stage of the disease,
      smoking habits have not been analyzed. Smoking is an interesting factor to
      consider since it is the main environmental risk factor for the development of
      rheumatoid arthritis (RA), a similar disease to CHIKV in many aspects. In the
      present study, 140 patients infected with CHIKV were assessed for risk factors
      associated with severe arthralgia intensity in the acute phase (pain of 9/10 on
      the visual analog scale of 0-10) and moderate to severe intensity (according to
      the Routine Assessment of Patient Index Data 3) 3.5 months after infection in
      patients that experienced the chronic phase of the disease. Women and smokers
      were 2- to 3-times more likely to experience severe pain in the acute and chronic
      stages. Likewise, the presence of severe arthralgia during the acute disease
      phase resulted in a 4-fold increased risk for entering the chronic phase. Smoking
      was a more important risk factor in males compared with females. Smoking resulted
      in a 20-fold increased risk for severe arthralgia during the acute phase in men,
      as well as a 10-fold increased risk for developing chronic disease with moderate
      to-severe pain 3.5 months after the acute stage. The presence of rash, headache,
      muscular weakness or conjunctivitis in the acute phase, the presence of diabetes
      and age >40 years were considered significant risk factors due to their influence
      on illness progression. In conclusion, smoking and female sex were the main risk
      factors associated with development of severe joint pain in the acute and chronic
      phases of Chikungunya fever. These risk factors are similar to those associated
      with the development and severity of RA, possibly because the two diseases share
      pathophysiological mechanisms, including elevated interleukin-6 levels.

PMID- 29467857
TI  - Overexpression of microRNA-15 increases the chemosensitivity of colon cancer
      cells to 5-fluorouracil and oxaliplatin by inhibiting the nuclear factor-kappaB
      signalling pathway and inducing apoptosis.
AB  - Overcoming chemoresistance is a challenge in clinical treatment. It has been
      reported that microRNAs (miRNAs) are involved in regulating chemosensitivity.
      Therefore, the present study aimed to identify the effect and mechanism of miR-15
      on colon cancer chemotherapy. Reverse transcription-quantitative polymerase chain
      reaction was performed to measure miR-15 level sin62-paired colon cancer and para
      cancerous colon tissues. The overexpression of miR-15 in HCT116 cells was induced
      by transfection. The effect of miR-15 on the chemosensitivity of colon cancer
      cells to 5-fluorouracil (5-FU) and Oxaliplatin (OX) was determined using a
      luminescent cell viability assay. Flow cytometry, dual-luciferase assay and
      western blot analysis were used to determine the potential mechanism of miR-15.
      The results suggested that the expression of miR-15 was decreased in tumour
      tissues and that overexpression of miR-15 increased the chemosensitivity of colon
      cancer cells to 5-Fu and OX. miR-15 promoted apoptosis in colon cancer cells
      treated with 5-Fu and OX by inhibiting the expression of p50, which repressed the
      expression of B cell lymphoma-2 and B cell lymphoma-extra large; two direct
      target genes of nuclear factor-kappaB with anti-apoptotic functions. Thus, the
      current study demonstrated that miR-15 increased the chemosensitivity of colon
      cancer cells to 5-FU and OX by inhibiting the NF-kappaB signalling pathway and
      inducing apoptosis.

PMID- 29467858
TI  - Effects of iodine-131 radiotherapy on Th17/Tc17 and Treg/Th17 cells of patients
      with differentiated thyroid carcinoma.
AB  - T helper 17 (Th17), T cytotoxic 17 (Tc17) and regulatory T (Treg) cells serve
      important roles in a number of inflammatory and autoimmune diseases. The aim of
      the present study was to examine the distribution of Th17, Tc17 and Treg cells in
      patients with differentiated thyroid cancer (DTC) prior to as well as 7, 30 and
      90 days following radioactive iodine-131 (131I) therapy, and to elucidate the
      probable effects of 131I therapy on Th17/Tc17 and Treg/Th17 cells in patients
      with DTC. A total of 40 patients with DTC (26 female; 14 male) between the ages
      of 24 and 72 years, as well as 13 age- and sex-matched healthy subjects were
      included in this study. The number of Th17, Tc17 and Treg cells in the peripheral
      blood of patients with DTC and of healthy Controls were assessed by flow
      cytometry. Th17 and Tc17 cells were counted as percentages of the number of CD3+
      T cells; Treg cells were counted as a percentage of the number of CD4+T cells. In
      addition, the serum levels of interleukin (IL)-17, IL-23, IL-10 and transforming
      growth factor (TGF)-beta1 were examined by ELISA. The frequencies of Th17, Tc17
      and Treg cells, as well as the serum levels of IL-17, IL-23, IL-10 and TGF-beta1
      were significantly elevated in patients with DTC compared with healthy Controls,
      whereas 131I therapy significantly decreased them. In addition, elevated
      Th17/Tc17 ratio and reduced Treg/Th17 ratio were observed in patients with DTC at
      day 0, however, these ratios returned to normal levels following 131I therapy for
      90 days as compared with healthy Controls. Notably, Th17/Tc17 and Treg/Th17
      ratios varied following 131I therapy for 7 and 30 days. In addition, a strong
      positive correlation between Th17 and Tc17 cells was observed in the healthy
      Controls and patients with DTC that received 131I treatment for 90 days, whereas
      a weak positive correlation between Th17 and Treg cell levels was identified in
      the healthy Controls and no obvious correlation between Th17 and Treg cells was
      observed in all patients with DTC pre- and post-131I therapy during the entire
      treatment period. These data suggested a significant involvement of Th17, Tc17
      and Treg cells in the pathology of DTC. Restoring the balance of these cells may
      contribute to the recovery of patients with DTC following 131I therapy.

PMID- 29467859
TI  - Fisetin inhibits the growth and migration in the A549 human lung cancer cell line
      via the ERK1/2 pathway.
AB  - Lung cancer is the most prevalent malignant tumor type in the developed world and
      the discovery of novel anti-tumor drugs is a research hotspot. Fisetin, a
      naturally occurring flavonoid, has been reported to have anti-cancer effects in
      multiple tumor types. The present study found that fisetin inhibited the growth
      and migration of non-small cell lung cancer in vitro. MTT, wound-healing, cell
      matrix adhesion and Transwell assays were performed and demonstrated that fisetin
      suppressed proliferation, migration, adhesion and invasion, respectively. Flow
      cytometric analysis indicated that fisetin induced apoptosis in the A549 cell
      line by decreasing the expression of c-myc, cyclin-D1, cyclooxygenase-2, B cell
      lymphoma-2, CXC chemokine receptor type 4, cluster of differentiation 44 and
      metalloproteinase-2/9, increasing the expression of cyclin dependent kinase
      inhibitor (CDKN) 1A/B, CDKN2D and E-cadherin and increasing the activity of
      caspase-3/9 via targeting the extracellular signal-regulated kinase signaling
      pathway. The results provided comprehensive evidence for the anti-tumor effects
      of fisetin in non-small cell lung cancer in vitro, which may provide a novel
      approach for clinical treatment.

PMID- 29467860
TI  - Roles of microRNA-539 and osteopontin in rheumatoid arthritis.
AB  - The present study aimed to investigate the role and mechanism of microRNA-539
      (miR-539) in rheumatoid arthritis (RA). A total of 68 RA patients and 46
      osteoarthritis patients were enrolled into the current study. Peripheral blood
      and joint fluid were collected prior to treatment. Reverse transcription
      quantitative polymerase chain reaction was performed to detect osteopontin (OPN)
      mRNA and miR-539 expression levels, while ELISA and western blot analysis were
      applied to detect OPN protein expression. In addition, bioinformatics analysis
      predicted that miR-539 directly targeted OPN, while dual-luciferase assay was
      used to validate this finding. Furthermore, agomiR-539 transfection and OPN
      knockdown by siRNA were conducted in MH7A cells, and MTT assay was used to detect
      MH7A cell proliferation. The results indicated that OPN was significantly
      increased in the blood and joint fluid of RA patients, while miR-539 expression
      was significantly decreased in the two types of specimens (P<0.05). Subsequent to
      silencing OPN by siRNA, the proliferation of MH7A cells was decreased (P<0.05).
      Following upregulation of miR-539, OPN expression was significantly decreased and
      cell proliferation was inhibited. Dual-luciferase assay revealed that miR-539
      regulated OPN expression through complementary binding to 3'-untranslated region.
      OPN was also significantly increased in the blood and joint fluid of RA patients,
      which may be associated with the downregulation of miR-539. Thus, miR-539 may
      promote the development and progression of RA through regulating OPN.

PMID- 29467861
TI  - Induction of apoptosis by an oleanolic acid derivative in SMMC-7721 human
      hepatocellular carcinoma cells is associated with mitochondrial dysfunction.
AB  - The aim of the present study was to investigate the effects of an oleanolic acid
      derivative, a novel antitumor drug, on the growth of SMMC-7721 human
      hepatocellular carcinoma cells and the underlying mechanism. An MTT assay was
      performed to determine the cytotoxicity of the oleanolic acid derivative. Cell
      membrane integrity was assessed using fluorescence microscopy to assess the
      uptake of annexin V-FITC/propidium iodide (PI). Western blotting was used to
      detect the apoptosis-associated proteins B cell lymphoma-2 (Bcl-2), Bax, caspase
      9 and caspase-3. A spectrophotometer was used to analyze the intracellular
      adenosine triphosphate (ATP) expression level. The loss of mitochondrial membrane
      potential was detected by performing the JC-1 assay. ELISA was used to evaluate
      the content of cytochrome c (Cyt-C). The oleanolic acid derivative reduced the
      cell viability of SMMC-7721 cells in a dose- and time-dependent manner. The half
      maximal inhibitory concentration values of the oleanolic acid derivative in SMMC
      7721 cells at 24, 48 and 72 h were 26.80, 11.85, and 6.66 uM, respectively. The
      antiapoptotic-protein Bcl-2 was downregulated, and the proapoptotic protein Bax
      was upregulated following treatment with the oleanolic acid derivative for 48 h.
      The oleanolic acid derivative induced the cleavage of caspase-9 and caspase-3 as
      well as promoted annexin V-FITC/PI uptake in SMMC-7721 cells. Furthermore,
      treatment of SMMC-7721 cells with the oleanolic acid derivative induced a
      reduction of the intracellular ATP expression level, loss of DeltaPsim and Cyt-C
      release from the mitochondria. The oleanolic acid derivative induced apoptosis in
      SMMC-7721 human cells. Mitochondrial dysfunction was involved in the anticancer
      effects of this derivative on SMMC-7721 human cells.

PMID- 29467862
TI  - Lentivirus-mediated silencing of HOTAIR lncRNA restores gefitinib sensitivity by
      activating Bax/Caspase-3 and suppressing TGF-alpha/EGFR signaling in lung
      adenocarcinoma.
AB  - Secondary resistance is a major limitation in the efficacy of epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitor treatment of lung cancer.
      Previous studies have shown that expression of the long non-coding RNA HOX
      transcript antisense RNA (HOTAIR) is upregulated in lung cancer, which is
      correlated with metastasis and poor prognosis. However, the precise role of
      HOTAIR and its effects on gefitinib resistance in human lung adenocarcinoma are
      not known. To address this issue, in the present study we established a gefitinib
      resistant (R)PC-9 human lung adenocarcinoma cell line and examined cell viability
      with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium assay. We found that gefitinib concentrations <10 uM
      inhibited the viability of PC-9 but not RPC-9 cells in a dose-dependent manner.
      Lentivirus-mediated HOTAIR RNA interference induced cell apoptosis and S-phase
      arrest, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling and flow cytometry. Consistent with these observations, HOTAIR
      suppression was associated with tumor shrinkage and restoration of gefitinib
      sensitivity in RPC-9 xenograft mice. Immunohistochemical analyses and western
      blot revealed that HOTAIR silencing resulted in the upregulation of B cell
      lymphoma 2-associated X protein (Bax), Caspase-3 and transforming growth factor
      alpha (TGF-alpha) and downregulation of EGFR and B cell lymphoma 2 (Bcl-2)
      levels. These results indicate that HOTAIR normally prevents the activation of
      Bax/Caspase-3 while inducing TGF-alpha/EGFR signaling. Thus, targeting HOTAIR may
      be a novel therapeutic strategy for treating gefitinib-resistant lung
      adenocarcinoma.

PMID- 29467863
TI  - Detection of EGFR and BRAF mutations by competitive allele-specific TaqMan
      polymerase chain reaction in lung adenocarcinoma.
AB  - Epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitors are the
      standard first-line treatment for patients with metastatic non-small cell lung
      cancer (NSCLC) expressing sensitive EGFR-mutants. Other drugs target different
      driver mutants, including the serine/threonine-protein kinase B-raf (BRAF)
      inhibitor dabrafenib, which has exhibited promising efficacy for treating
      patients with metastatic BRAF-mutated NSCLC. Therefore, identifying patients
      carrying mutations that may be treated using targeted therapies is important.
      However, the methods of molecular detection presently applied in clinical
      practice, particularly detection of BRAF in NSCLC patients, require further
      investigation. Therefore, more sensitive and economic methods are required. The
      present study applied the competitive allele-specific TaqMan polymerase chain
      reaction (CastPCR) technology to the molecular detection of EGFR (del2235-2249,
      del2236-2250, T790M, L858R) and BRAF (V600E, G469A, D594G) mutations in 144
      treatment-naive patients with lung adenocarcinoma, and analyzed the association
      between the mutation rates and patients' clinicopathological features. 51.4%
      (74/144) cases were identified harboring EGFR mutations. A total of 40.3%
      (58/144) patients carried sensitizing mutations (exon 19 deletion or L858R) and
      14.6% (21/144) carried T790M mutations. 6.9% (10/144) mutation-positive patients
      were double-mutated. Total EGFR mutation rate was significantly increased in
      female compared with that of males (60.9 vs. 43.8%, P<0.05), in non-smokers
      compared with that of smokers (62.8 vs. 34.5%, P<0.05). In total, 8.3% (12/144)
      patients were identified with BRAF mutations. 16.7% were V600E (2/12) and 83.3%
      (10/12) were non-V600E mutants. Among the 10 non-V600E mutations, D594G accounted
      for 90.0% (9/10) and G469A accounted for 10.0% (1/10). Statistical analysis
      demonstrated that the BRAF mutation rate was not associated with any of the
      following clinicopathological features: Sex, age, smoking history, clinical
      stages, distant metastasis, differentiation degree, tumor size and regional lymph
      node metastasis (P>=0.05). CastPCR technology is a robust method with high
      sensitivity for the molecular detection of EGFR and BRAF mutations in clinical
      formalin-fixed paraffin-embedded samples.

PMID- 29467864
TI  - Therapeutic targeting of noncoding RNAs in hepatocellular carcinoma: Recent
      progress and future prospects.
AB  - Due to the high mortality rate and unsatisfactory treatment options available,
      hepatocellular carcinoma (HCC) remains one of the most common malignancies and a
      leading cause of cancer-associated mortality. Novel therapeutic targets for HCC
      are urgently required. Advanced RNA sequencing technology enables the
      identification of considerable amounts of noncoding RNAs (ncRNAs), including
      small noncoding RNAs and long noncoding RNAs, which exhibit no protein-coding
      activities. In this respect, ncRNAs and their regulatory processes are important
      factors in liver tumorigenesis. The present review focuses on the characteristics
      and biological roles of ncRNAs in HCC. Potential therapeutic applications of
      ncRNAs in HCC are also evaluated.

PMID- 29467865
TI  - Discoidin domain receptor 1: New star in cancer-targeted therapy and its complex
      role in breast carcinoma.
AB  - Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by
      various types of collagens that performs a critical role in cell attachment,
      migration, survival and proliferation. The functions of DDR1 in various types of
      tumor have been studied extensively. However, in breast carcinoma, the roles of
      collagen-evoked DDR1 remain ill defined. Although a number of studies have
      reported that DDR1 promotes apoptosis and inhibits migration in breast carcinoma,
      it has also been reported to be associated with tumor cell survival,
      chemoresistance to genotoxic drugs and the facilitation of invasion. The present
      review summarizes current progress and the complex effects of DDR1 in the field
      of breast carcinoma, and presents DDR1 as a promising therapeutic target.

PMID- 29467866
TI  - Notch signaling and non-small cell lung cancer.
AB  - Lung cancer is the leading cause of cancer-associated mortality worldwide.
      Elucidation of the pathogenesis and biology of lung cancer is critical for the
      design of an effective treatment for patients. Non-small cell lung cancer (NSCLC)
      accounts for 80-85% of lung cancer cases. The abnormal expression of Notch
      signaling pathway members is a relatively frequent event in NSCLC. The Notch
      signaling pathway serves important roles in cell fate determination,
      proliferation, differentiation and apoptosis. Increasing evidence supports the
      association of Notch signaling dysregulation with various types of malignant
      tumor, including NSCLC. Several studies have demonstrated that members of the
      Notch signaling pathway may be potential biomarkers for predicting the
      progression and prognosis of patients with NSCLC. Furthermore, Notch signaling
      serves critical roles in the tumorigenesis and treatment resistance of NSCLC
      cells by promoting the proliferation or inhibiting the apoptosis of NSCLC cells.
      The present review provides a detailed summary of the roles of Notch signaling in
      NSCLC.

PMID- 29467867
TI  - Low-molecular-weight polysaccharides from Agaricus blazei Murrill modulate the
      Th1 response in cancer immunity.
AB  - To assess the effect of low-molecular-weight polysaccharides from Agaricus blazei
      Murrill (ABP-AW1) as an immunoadjuvant therapy for type 1 T-helper (Th1)
      responses in tumorigenesis, C57BL/6 mice were inoculated subcutaneously with
      ovalbumin (E.G7-OVA). After 3, 10 and 17 days, the mice were immunized with PBS,
      OVA alone, or OVA and ABP-AW1, at low (50 ug), intermediate (100 ug) or high (200
      ug) doses. Tumor growth was examined and compared among the groups, as were the
      following parameters: Splenocyte viability/proliferation, peripheral blood
      CD4+/CD8+ T cell ratio, serum OVA-specific IgG1 and IgG2b, secretion of
      interleukin (IL)-2 and interferon (IFN)-gamma, and IFN-gamma production on a
      single cell level from cultured splenocytes. Tumor growth in mice treated with
      OVA and ABP-AW1 (100 or 200 ug) was significantly slower, compared with in the
      other groups at the same time-points. OVA with 100 or 200 ug ABP-AW1 was
      associated with a higher number of total splenocytes, a higher ratio of
      peripheral blood CD4+/CD8+ T-lymphocytes, higher serum levels of OVA-specific Th1
      type antibody IgG2b and greater secretion of the Th1 cytokines IL-1 and IFN-gamma
      from splenocytes. ABP-AW1 is a promising immunoadjuvant therapy candidate, due to
      its ability to boost the Th1 immune response when co-administered with a cancer
      vaccine intended to inhibit cancer progression.

PMID- 29467868
TI  - Angiogenesis for tumor vascular normalization of Endostar on hepatoma 22 tumor
      bearing mice is involved in the immune response.
AB  - Tumor vascular normalization involved in immune response is beneficial to the
      chemotherapy of tumors. Recombinant human endostatin (Endostar), an angiogenesis
      inhibitor, has been demonstrated to be effective in hepatocellular cancer (HCC).
      However, its vascular normalization in HCC and the role of the immune response in
      angiogenesis were unclear. In the present study, effects of Endostar on tumor
      vascular normalization were evaluated in hepatoma 22 (H22) tumor-bearing mice.
      Endostar was able to inhibit the proliferation and infiltration of tumor cells
      and improve alpha-fetoprotein, tumor necrosis factor-alpha and cyclic adenosine
      5'-phosphate levels in the serum of H22-bearing mice, as well as the protein
      expression levels of the immune factors interferon-gamma and cluster of
      differentiation (CD)86 in liver tissue. Endostar also exhibited more marked
      downregulation of the levels of vascular endothelial growth factor, CD31, matrix
      metalloproteinase (MMP)-2, MMP-9 and interleukin-17 during day 3-9 treatment,
      resulting in short-term normalization of tumor blood vessels. The period of
      vascular normalization was 3-9 days. The results of the present study
      demonstrated that Endostar was able to induce the period of vascular
      normalization, contributing to a more efficacious means of HCC treatment combined
      with other chemotherapy, and this effect was associated with the immune response.
      It may be concluded that Endostar inhibited immunity-associated angiogenesis
      behaviors of vascular endothelial cells in response to HCC. The results of the
      present study provided more reasonable possibility for the combination therapy of
      Endostar for the treatment of HCC.

PMID- 29467869
TI  - Role of epithelial-mesenchymal transition markers E-cadherin, N-cadherin, beta
      catenin and ZEB2 in laryngeal squamous cell carcinoma.
AB  - Epithelial-mesenchymal transition (EMT) allows neoplastic cells to gain the
      invasive phenotype and become migratory, which is required for cancer progression
      and metastasis. In the present study, the expression of EMT-associated biomarkers
      and their association with clinicopathological parameters in laryngeal squamous
      cell carcinoma (LSCC) was investigated. E-cadherin, N-cadherin, beta-catenin and
      zinc finger E-box binding homeobox 2 (ZEB2) protein expression was evaluated with
      immunohistochemistry in a cohort of 76 patients with operable LSCC. The
      association between these transition markers, clinicopathological parameters and
      their prognostic impact in LSCC was analyzed. Immunohistochemical analysis
      revealed that EMT-associated proteins were differentially expressed between LSCC
      and adjacent non-neoplastic laryngeal tissue. Negative E-cadherin expression and
      positive N-cadherin, beta-catenin and ZEB2 expression were associated with a
      later tumor (T) stage, decreasing tumor differentiation and a reduced overall
      survival (OS) time (OS: E-cadherin, P=0.016; N-cadherin, P=0.003; beta-catenin,
      P=0.002; ZEB2, P=0.0003). E-cadherin/beta-catenin co-expression was significantly
      associated with the majority of clinicopathological parameters assessed,
      including lymph node metastases, T stage and tumor cell differentiation (P=0.004,
      P=0.005, and P<0.001, respectively). Multivariate analysis indicated that T stage
      and the positive expression of beta-catenin and ZEB2 were independent risk
      factors for OS in LSCC (P=0.014, P=0.025 and P=0.003, respectively). It was
      concluded that EMT mediates tumor progression, and reduces OS time in patients
      with LSCC. E-cadherin/beta-catenin co-expression may be associated with
      clinicopathological parameters. T stage, and the positive co-expression of beta
      catenin and ZEB2 may be independent predictors of prognosis in LSCC.

PMID- 29467870
TI  - HIF-1alpha promotes ZEB1 expression and EMT in a human bladder cancer lung
      metastasis animal model.
AB  - Lung is one of the most common sites for bladder cancer to metastasize. Although
      the involvement of the epithelial-to-mesenchymal transition (EMT) in bladder
      cancer progression has been established, the mechanism of EMT induction remains
      unclear. In order to investigate this, T24-parental (P) and T24-lung (L) bladder
      cancer cells were obtained from primary tumors and lung metastatic sites of an
      animal model with orthotopic spontaneous metastatic bladder cancer, according to
      a protocol previously described. Compared with T24-P cells, mesenchymal-like T24
      L cells exhibited an increased ability in tumor invasion and metastasis, as well
      as an increased expression of hypoxia-inducible factor (HIF)-1alpha, zinc finger
      E-box-binding homeobox 1 (ZEB1), vimentin and N-cadherin and lower level of
      cytokeratin 18 were observed. Mechanistically, it was identified that HIF-1alpha
      increases ZEB1 expression and subsequently regulates the expression of EMT
      related genes in both HIF-1alpha knocking down by siRNA and gain-in HIF-1alpha by
      hypoxia culture cell models. In addition, the expression of HIF-1alpha and ZEB1
      in bladder cancer tissues were increased compared with normal bladder epithelial
      tissues, as well as significantly increased in the high-grade, invasive and
      metastatic bladder cancer tissues compared with low-grade, superficial and non
      metastatic bladder cancer tissues by using immune-histochemical staining assay.
      Notably, the protein level of HIF-1alpha was positively associated with that of
      ZEB1 in bladder cancer tissues. Results from the present study indicate that HIF
      1alpha promotes ZEB1 expression and EMT in the T24-L human bladder cancer lung
      metastasis animal model, suggesting that HIF-1alpha serves an important function
      in the metastasis of bladder cancer, and HIF-1alpha and ZEB1 may be potential
      targets for inhibiting bladder metastasis in the future.

PMID- 29467871
TI  - Abnormal expression of circulating and tumor-infiltrating carcinoembryonic
      antigen-related cell adhesion molecule 1 in patients with glioma.
AB  - Glioma, the most prevalent primary tumor of the central nervous system, is known
      to evade immune surveillance and escape immune attacks by inducing
      immunosuppression. The homophilic interactions of the carcinoembryonic antigen
      related cell adhesion molecule 1 (CEACAM1) serve a critical function in
      immunoregulation. In the present study, the expression levels of CEACAM1 in
      peripheral blood mononuclear cells and tumor-infiltrating lymphocytes (TILs) from
      patients with gliomas were assessed. Furthermore, associations between CEACAM1
      expression and multiple clinicopathological characteristics in patients with
      gliomas were analyzed. The results of the present study suggested that the
      expression of CEACAM1 in circulating T cells was markedly increased in patients
      with gliomas compared with control subjects, and was further increased in TILs.
      Patients with high-grade gliomas [World Health Organization (WHO) grade III-IV]
      demonstrated a significantly increased expression of CEACAM1 on T cells compared
      with those with low-grade gliomas (WHO grade I-II). Furthermore, the expression
      of CEACAM1 on T cells was negatively correlated with the Karnofsky score and the
      plasma level of interferon-gamma in patients with gliomas. Immunohistochemical
      analysis revealed that the expression levels of CEACAM1 in high-grade glioma
      tissues (WHO grade III-IV) were increased compared with the expression levels in
      the controls, and were associated with the expression of CEACAM1 in TILs. In
      summary, the results of the present study indicate that homophilic interactions
      of CEACAM1 may participate in the progression and development of gliomas through
      their negative regulatory effects on T cells. Thus, CEACAM1 may be a promising
      candidate for targeted glioma immunotherapy.

PMID- 29467872
TI  - Differential microRNA expression profiles in tamoxifen-resistant human breast
      cancer cell lines induced by two methods.
AB  - Tamoxifen (TAM) resistance has become a severe problem for endocrine therapy of
      breast cancer. The present study investigated the association between microRNA
      (miRNA) expression and TAM resistance in breast cancer. The TAM-resistant breast
      cancer MCF-7C and MCF-7T cell lines were established using the human breast
      cancer cell line MCF-7 as the parental cell line and 4-hydroxytamoxifen (OHT) as
      the screening drug in vitro. The MCF-7C cell line was established by dose
      stepwise induction beginning with a low concentration of OHT; the MCF-7T cell
      line was established by temporal stepwise induction beginning with a high
      concentration of OHT. Differential miRNA expression profiles between TAM
      sensitive (MCF-7) and TAM-resistant (MCF-7C and MCF-7T) breast cancer cell lines
      were detected and analyzed using RNA sequencing technology. The results of
      western blot analysis indicated that the level of ERalpha protein expression in
      drug-resistant cells was significantly increased. A total of 1,646 miRNAs were
      detected in all samples, including 1,376 known miRNAs and 270 predicted miRNAs.
      There were 118 miRNAs expressed at significantly different levels between MCF-7C
      and MCF-7 cells (P<0.05); among them, 67 miRNAs were upregulated (P<0.05) and 51
      miRNA were downregulated (P<0.05). There were 42 miRNAs expressed at
      significantly different levels between MCF-7T and MCF-7 (P<0.05); among them, 23
      miRNAs were upregulated (P<0.05) and 19 miRNAs were downregulated (P<0.05). There
      were 126 miRNAs with significant differences between MCF-7C and MCF-7T (P<0.05);
      among them, 76 miRNAs were upregulated (P<0.05) and 50 miRNAs were downregulated.
      On the basis of the results of the present study, we hypothesize that miR-21, miR
      146a, miR-148a, miR-34a and miR-27a may serve important roles in mediating TAM
      resistance in breast cancer, and have potential as therapeutic targets for TAM
      resistant breast cancer.

PMID- 29467873
TI  - Utility of Survivin, BAP1, and Ki-67 immunohistochemistry in distinguishing
      epithelioid mesothelioma from reactive mesothelial hyperplasia.
AB  - Histological distinction between epithelioid mesothelioma (EM) and reactive
      mesothelial hyperplasia (RMH) can be challenging. The aim of this study was to
      assess the diagnostic utility of Survivin, Ki-67, and loss of BRCA1-associated
      protein 1 (BAP1) expressions in distinguishing EM from RMH using
      immunohistochemistry. Formalin-fixed, paraffin-embedded specimens from 78 cases
      of EM and 80 cases of RMH were immunohistochemically examined for Survivin, BAP1,
      and Ki-67. In addition, receiver operating characteristic curve analyses were
      performed to establish the cut-off values for Survivin and Ki-67 labelling
      indices. Survivin (cut-off value: 5%) had 67.7% sensitivity and 100% specificity,
      while Ki-67 (cut-off value: 10%) had 85.1% sensitivity and 87.5% specificity, and
      BAP1 had 66.2% sensitivity and 100% specificity for the differentiation of EM
      from RMH. Among the combinations of two markers, the combination of Survivin and
      BAP1 (Survivin-positive and/or BAP1-loss finding) had the highest diagnostic
      accuracy (sensitivity: 89.8%; specificity: 100%; accuracy: 95.3%). We recommend
      using the combination of Survivin and BAP1 to distinguish EM from RMH.

PMID- 29467874
TI  - Effects of NOB1 on the pathogenesis of osteosarcoma and its expression on the
      chemosensitivity to cisplatin.
AB  - The effects of NIN1/RPN12 binding protein 1 homolog (NOB1) on the pathogenesis of
      osteosarcoma and its expression on the chemosensitivity to cisplatin were
      investigated. Seventy-four patients with osteosarcoma who received surgical
      resection in The Affiliated Hospital of Southwest Medical University (Sichuan,
      China) from September 2013 to September 2016 were enrolled in this study. The
      expression of NOB1 in cancer and cancer-adjacent tissues of patients was detected
      by reverse transcription-polymerase chain reaction, and the relationship between
      NOB1 expression and the pathogenesis of osteosarcoma was analyzed. The expression
      of NOB1 in osteosarcoma MG-63 cells was interfered with using small interfering
      ribonucleic acid (siRNA). Western blotting was used to detect the transfection
      efficiency and changes in apoptosis indicators. Cell Counting Kit-8 (CCK-8) assay
      was used to examine changes in the sensitivity of cells to cisplatin. The effect
      of NOB1 knockout on cell apoptosis was examined by flow cytometry. In patients
      with osteosarcoma, the level of NOB1 mRNA in cancer tissues was significantly
      higher than that in cancer-adjacent tissues (p<0.05), and the expression of NOB1
      was correlated with Ennecking staging and tumor size (p<0.05). The expression
      level of the apoptotic indicator caspase-3 was activated after siRNA interfered
      with NOB1 expression, thus reducing the expression level of anti-apoptotic
      indicator B-cell lymphoma 2. CCK-8 results showed that the downregulation of NOB1
      increased the sensitivity of MG-63 cells to cisplatin (p<0.05). In addition, flow
      cytometry showed that the downregulation of NOB1 significantly promoted the
      apoptosis of MG-63 cells. NOB1 is significantly upregulated in patients with
      osteosarcoma, thus reducing the curative effect of cisplatin chemotherapy, which
      indicates that the prognosis is poor.

PMID- 29467875
TI  - Potential prognostic biomarkers identified by DNA methylation profiling analysis
      for patients with lung adenocarcinoma.
AB  - Lung adenocarcinoma is frequently occurring type of lung cancer with high
      metastatic risk. We performed a DNA methylation profiling analysis to identify
      possible prognostic markers involved in lung adenocarcinoma. DNA methylation
      profiling data (GSE66386) were downloaded from the Gene Expression Omnibus (GEO)
      database. Differentially methylated genes were identified using a limma package.
      GO enrichment analysis was performed to identify vital functions related to
      differential gene methylation, and pathway analysis was performed to assess the
      associations between different proteins with regard to regulation of cell
      function and metabolism. The screening results showed a total of 112,662
      differentially methylated genes in lung adenocarcinoma patients compared with
      those of the normal controls. These CpGs were involved in 16,705 genes. The
      skeletal system development (P=9.46E-27) and embryonic organ morphogenesis
      (P=8.67E-24) were found to be involved in lung adenocarcinoma. The cancer
      (P=3.64E-07), Rap1 signaling (P=9.21E-05) and calcium signaling (P=9.21E-05)
      pathways constituted the important pathways associated with lung adenocarcinoma.
      In conclusion, methylated PTPRF, HOXD3, HOXD13 and CACNA1A are potential markers
      and may be utilized for the diagnosis and therapy of lung adenocarcinoma.

PMID- 29467876
TI  - Comparison of the safety of the application of painless gastroscopy and ordinary
      gastroscopy in chronic hypertension patients combined with early gastric cancer.
AB  - The aim of the present study was to compare the safety of the application of
      painless gastroscopy and ordinary gastroscopy for chronic hypertension patients
      combined with early gastric cancer. A total of 123 patients with early gastric
      cancer were selected at the Dongying People's Hospital from June, 2014 to August,
      2016. The patients were randomly divided into the painless (n=63) and ordinary
      (n=60) gastroscopy groups. Proper pretreatment was performed according to whether
      anesthesia was performed or not. Arterial pressure, heart rate, and blood oxygen
      saturation were detected and compared before anesthesia, when gastroscope passed
      through the esophageal entrance plane, and after recovery from anesthesia. The
      incidence of nausea and vomiting, cough, dysphoria, throat discomfort and other
      adverse reactions during and after surgery were recorded and compared. Compared
      with the levels before anesthesia, the mean arterial pressure, heart rate and
      blood oxygen saturation were significantly reduced in painless gastroscopy when
      the gastroscope passed through the esophageal entrance plane (P<0.05). In the
      ordinary gastroscopy group, the mean arterial pressure, heart rate and blood
      oxygen saturation were significantly increased when the gastroscope passed
      through the esophageal entrance plane compared with the levels before anesthesia
      (P<0.05). Blood pressure decreased in the painless gastroscopy group whereas it
      increased in the ordinary gastroscopy group after anesthesia. The decrease in the
      painless gastroscopy group was lower than in the ordinary group. The incidence of
      intraoperative and postoperative adverse reactions including nausea, vomiting,
      cough, dysphoria, pharyngeal discomfort and other adverse reactions was
      significantly decreased in the painless gastroscopy group than in the ordinary
      gastroscopy group (P<0.05). The results suggest that the application of painless
      gastroscopy in chronic hypertension patients can significantly reduce the
      incidence of intraoperative and postoperative adverse reactions compared with
      that of the Gastric cancer ordinary gastroscopy. Thus, painless gastroscopy is
      safer than ordinary gastroscopy.

PMID- 29467877
TI  - Rapid detection of quantum dot immune chromatography nasopharyngeal carcinoma
      EBNA1 antibody.
AB  - This study explored the 605 nm carboxyl of water-soluble quantum dots to assess
      the practicability of the nasopharyngeal carcinoma marker EBNA1 antibody. We used
      605 nm carboxyl water-soluble quantum dots and nasopharyngeal carcinoma EBNA1
      antigen in 1-(3-dimethylaminopropyl-3-2-ethylcarbonimine hydrochloride to
      generate quantum dot-labeled antigen. Gel imaging system showed that serum group
      and 60 patients with nasopharyngeal carcinoma had significant differences in 30
      cases of normal adult serogroup brightness, Levene test in the two groups ELISA
      absorbance value was P<0.001, namely the nasopharyngeal carcinoma group and the
      normal adult serum group measured absorbance value difference was obvious. The
      statistical significance, and the detection technology were of high specificity
      and sensitivity. In conclusion, this study adopted double antigen clip combining
      immune chromatography test EBNA1 antibody in serum, compared with the traditional
      enzyme-linked immunoassays this method is more rapid, with simpler operation,
      rapid detection for developing quantum dot immune chromatography technology the
      EBNA1 antibody kit provides a theoretical basis.

PMID- 29467878
TI  - Parthenolide facilitates apoptosis and reverses drug-resistance of human gastric
      carcinoma cells by inhibiting the STAT3 signaling pathway.
AB  - In the present study, SGC-7901/DDP cells were treated with different
      concentrations of parthenolide (PN) (2.5-15 umol/l), cisplatin (DDP) (1.25-15
      ug/ml) and PN+DDP. The proliferation inhibition rates were measured using an MTT
      assay, and the synergies of PN and DDP were analyzed. The effect of PN and DDP on
      SGC-7901/DDP cell proliferation demonstrated a time- and concentration-dependent
      association, and a synergy between PN and DDP was identified. DAPI staining and
      flow cytometry results indicated that 15 umol/l PN significantly induced SGC
      7901/DDP apoptosis and G1 phase arrest compared with the untreated control group.
      Western blotting analysis results indicated that among the apoptosis-associated
      proteins, there were dose-dependent increases in the protein expression of
      apoptosis regulator BAX, cellular tumor antigen p53, cleaved caspase-3 and
      cleaved capase-9, and decreases in apoptosis regulator Bcl-2 and Bcl-xL protein
      expression levels. Among the cell cycle-associated proteins, cyclin D1 expression
      was significantly decreased, cyclin-dependent kinase inhibitor 1 expression was
      significantly increased, and signal transducer and activator of transcription 3
      (STAT3) activation was inhibited. Scratch and Transwell assay results revealed
      that PN significantly inhibited SGC-7901/DDP cell migration, and invasion. The
      present study demonstrated that PN induces SGC-7901/DDP apoptosis, inhibits SGC
      7901/DDP proliferation, migration and invasion, and enhances the drug sensitivity
      of the cells to DDP. The underlying mechanisms may be associated with inhibition
      of the STAT3 signaling pathway and regulation of the downstream apoptotic protein
      and cyclin expression levels.

PMID- 29467879
TI  - Loss of CDX2 gene expression is associated with DNA repair proteins and is a
      crucial member of the Wnt signaling pathway in liver metastasis of colorectal
      cancer.
AB  - Caudal type homeobox 2 (CDX2) has been well-established as a diagnostic marker
      for colorectal cancer (CRC); however, less is known about its regulation,
      particularly its potential interactions with the DNA repair proteins, adenomatous
      polyposis coli (APC) and beta-catenin, in a non-transcriptional manner. In the
      present study, the protein expression of CDX2 was analyzed, depending on the
      expression of the DNA repair proteins, mismatch repair (MMR), O6-methylguanine
      DNA methyltransferase (MGMT) and excision repair cross-complementing 1 (ERCC1),
      and its importance in Wnt signaling was also determined. A total of 101 liver
      metastases were punched into tissue microarray (TMA) blocks and serial sections
      were cut for immunohistochemistry. For each protein, an immunoreactive score was
      generated according to literature data and the scores were fitted to TMA.
      Subsequently, statistical analysis was performed to compare the levels of
      expression with each other and with clinical data. CDX2 loss of expression was
      observed in 38.5% of the CRC liver metastasis cases. A statistically significant
      association between CDX2 and each of the investigated MMRs was observed: MutL
      Homolog 1 (P<0.01), MutS protein Homolog (MSH) 2 (P<0.01), MSH6 (P<0.01), and
      postmeiotic segregation increased 2 (P=0.040). Furthermore, loss of MGMT and
      ERCC1 was also associated with CDX2 loss (P=0.039 and P<0.01, respectively). In
      addition, CDX2 and ERCC1 were inversely associated with metastatic tumor size
      (P=0.038 and P=0.027, respectively). Sustained CDX2 expression was associated
      with a higher expression of cytoplasmic/membranous beta-catenin and with nuclear
      APC expression (P=0.042 and P<0.01, respectively). In conclusion, CDX2 loss of
      expression was not a rare event in liver metastasis of CRC and the results
      suggested that CDX2 may be involved in mechanisms resulting in the loss of DNA
      repair protein expression, and in turn methylation; however, its exact function
      in this context remains to be elucidated.

PMID- 29467880
TI  - The role of immune cell subpopulations in the growth and rejection of TC-1/A9
      tumors in novel mouse strains differing in the H2-D haplotype and NKC domain.
AB  - The present study aimed to elucidate the role of cluster of differentiation
      (CD)8+, CD4+, natural killer (NK), and myeloid (CD11b+) cells in the course of
      the growth and rejection of experimental major histocompatibility complex (MHC)
      class I-deficient, HPV16 E6/E7-associated TC-1/A9 tumors in mice. Stable mouse
      lines (F30) generated by inbreeding of Balb/c and C57BL/6 strains, which were
      characterized by H-2Db+d-NK1.1neg (B6-neg) and H-2Db-d+NK1.1high (Balb-high)
      phenotypes, were used for the present study. The novel strains spontaneously
      regressed tumors in 70-90% of cases. Ex vivo histological analysis of the tumor
      microenvironment in cryosections showed an indirect correlation between the
      growth of the transplanted tumor (progressor vs. regressor mice) and the
      proportion of immunocompetent cell infiltration in the tumors. The regressor mice
      exhibited a higher infiltration of tumors with CD4+ and CD8+ cells, and in Balb
      high with NK cells as well, compared with the progressors. All tumor transplants
      also indicated a huge infiltration of CD11b+ cells, but this infiltration was not
      dependent on the stage of the TC-1/A9 tumor development. Depletion of individual
      cell subpopulations in vivo exhibited different effects on the tumor development
      in the two strains. Elimination of CD8-positive cells enhanced growth of TC-1/A9
      tumor transplants in both hybrid stains, whereas CD4+ cell depletion affected
      rejection of TC-1/A9 tumors in the B6-neg mice only. Depletion of NK cells with
      anti-asialo GM1 antibody in the Balb-high strain led to enhancement of tumor
      growth, which was more pronounced after depletion of the NK1.1+ subpopulation. On
      the other hand, depletion of NK cells with anti-asialo GM1 in B6-neg mice did not
      affect the regression of TC-1/A9 tumor transplants, but increased the CD11b+ cell
      infiltration. In summary, these results indicate that co-operation of particular
      subsets of immunocompetent cells is essential for the rejection of TC-1/A9 tumor
      transplants. In B6-neg mice, the co-operative action of CD8+ and CD4+ cells is
      required, whereas in Balb-high mice, the synergy of CD8+ and NK1.1+ cells is of
      major importance.

PMID- 29467881
TI  - Diffuse large B-cell lymphoma: 10 years' real-world clinical experience with
      rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone.
AB  - Treatment with rituximab plus a regimen of cyclophosphamide, doxorubicin,
      vincristine and prednisolone (CHOP) for patients with diffuse large B-cell
      lymphoma (DLBCL) has proven efficacy in clinical trials. The present study
      investigated its application in clinical practice. This single-center,
      retrospective database analysis included patients with DLBCL treated at the
      Slovenian Institute of Oncology Ljubljana between 2004 and 2013. Overall survival
      (OS) and progression-free survival (PFS) were assessed according to International
      Prognostic Index (IPI) and revised IPI (R-IPI) categories. Overall, 573 patients
      with DLBCL were included in the study (median follow-up, 45.3 months; range, 0.1
      143.0). Patients were categorized as IPI 'low' (n=170; 30%), 'low-intermediate'
      (n=134; 23%), 'high-intermediate' (n=129; 23%) and 'high' (n=140; 24%) risk. R
      IPI groups were indicated with 'very good' (n=59; 10%), 'good' (n=245; 43%) and
      'poor' (n=269; 47%) prognosis. Ten-year OS and PFS rates were 51 and 72%,
      respectively; median OS was 124 months and median PFS was not reached. Ten-year
      OS rates were 80 and 87% in low-risk and 'very good' prognosis groups,
      respectively, and 30 and 37% in high-risk and poor prognosis patients,
      respectively. This analysis of patients with DLBCL indicated that many patients
      treated with R-CHOP and R-CHOP-like regimens in the real-world setting have
      excellent outcomes.

PMID- 29467882
TI  - Primary pulmonary intravascular large B-cell lymphoma: A report of three cases
      and literature review.
AB  - The present study aimed to investigate the clinicopathological features of
      primary intravascular large B-cell lymphoma (IVLBCL) of the lung. The clinical
      and histopathological data of three patients, and the literature was reviewed.
      The Ethics Committees of Drum Tower Hospital approved the current study based on
      the three cases. Fever and respiratory symptoms were the main presenting
      symptoms. Serum lactate dehydrogenase and C-reactive protein were significantly
      increased. Diffuse ground glass opacities or nodular consolidations were seen on
      high resolution computed tomography. Lung biopsy revealed lymphoma cells in the
      lumen of small blood vessels. Tumor cells expressed cluster of differentiation 20
      and melanoma associated antigen (mutated) 1. Primary pulmonary IVLBCL is
      extremely rare and its prognosis is poor. Full recognition of its clinical
      character and improvement of the diagnostic awareness may help to reduce missed
      diagnosis, and facilitate appropriate treatment.

PMID- 29467883
TI  - Effects of Yangzheng Sanjie Decoction-containing serum mediated by microRNA-7 on
      cell proliferation and apoptosis in gastric cancer.
AB  - Gastric cancer (GC) is one of the most common types of cancer and a leading cause
      of cancer-associated mortality. MicroRNAs (miRNAs/miRs) are demonstrated to
      function as oncomiRs or tumor-suppressor-miRs in GC. miR-7 has been identified to
      be a tumor suppressor of GC by targeting epidermal growth factor receptor (EGFR).
      In our previous study, Yangzheng Sanjie Decoction (YZSJD), a traditional Chinese
      formula, was identified to be effective in alleviating the symptoms and even
      postponing turnover of precancerous lesions. To elucidate the mechanism of YZSJD,
      the present study evaluated the effects of YZSJD of the GC MKN-45 cell line and
      investigated the underlying molecular mechanisms using YZSJD-containing serum
      (YCS). The expression of miR-7 in GC, normal and adjacent tissue samples was
      examined. The results demonstrated that YCS inhibited proliferation by inducing
      cell cycle arrest at the S phase, and significantly induced apoptosis compared
      with the control group. miR-7 was significantly downregulated in GC tissues
      compared with the matched ones. Using reverse transcription-quantitative
      polymerase chain reaction and western blot analysis, the expression of miR-7 was
      inversely associated with EGFR. This indicates that YCS inhibits proliferation
      and induces apoptosis of GC cells mediated by miR-7 targeting EGFR, which may be
      one of the mechanisms whereby YZSJD exerts its effects on GC.

PMID- 29467884
TI  - Etaypoxia-inducible factor 1-alpha promotes colon cell proliferation and
      migration by upregulating AMPK-related protein kinase 5 under hypoxic conditions.
AB  - Hypoxia is a common characteristic of solid tumors. Previous studies have
      reported that the tumor invasion-associated factor, AMPK-related protein kinase 5
      (ARK5), is associated with a poor prognosis in colon cancer. However, whether or
      not ARK5 is involved in hypoxia is unclear. The aim of present study was to
      investigate the association between the expression of ARK5 and that of hypoxia
      inducible factor 1-alpha (HIF1-alpha). Samples from 60 patients with colon cancer
      were collected and immunohistochemistry was used to detect the expression of ARK5
      and HIF1-alpha within them. Western blot analysis and reverse transcription
      polymerase chain reaction were used to detect the expression of ARK5 in an SW480
      cell line under hypoxic conditions. Cell Counting kit-8 and Transwell assays were
      used to study the function of ARK5 under hypoxic conditions. According to the
      immunohistochemistry results, ARK5 and HIF1-alpha staining was significantly
      associated with Tumor-Node-Metastasis stage, tumor grade, lymph node metastasis
      and liver metastasis. Spearman's correlation analysis revealed a correlation
      between the expression of ARK5 and that of HIF1-alpha. This finding was also
      verified under hypoxic conditions in the SW480 cell line, in which the expression
      of ARK5 increased over time. Further cellular function experiments revealed that
      suppression of ARK5 inhibited cell viability and migration under hypoxic
      conditions. The present study has suggested that ARK5 expression in colon cancer
      cells is upregulated by HIF1-alpha under hypoxic conditions and that ARK5 serves
      an important role in cell proliferation and migration under hypoxic stress.

PMID- 29467885
TI  - Paclitaxel plus nedaplatin vs. paclitaxel plus carboplatin in women with
      epithelial ovarian cancer: A multi-center, randomized, open-label, phase III
      trial.
AB  - The multi-center, randomized, open-label, phase III trial discussed in the
      present study was performed to compare the clinical outcomes of nedaplatin (NDP)
      plus paclitaxel, and carboplatin (CBP) plus paclitaxel for the treatment of
      epithelial ovarian cancer (EOC). In the current study, 182 patients with
      International Federation of Gynecology and Obstetrics (FIGO) stage II-IV EOC were
      randomly assigned to receive NDP plus paclitaxel or CBP plus paclitaxel at 3-week
      intervals for a total of six courses. The primary endpoints were progression-free
      survival rate (PFS) and overall survival rate (OS). The secondary endpoints were
      toxicity profiles. The median follow-up was 44.63 months [95% confidence interval
      (CI) 33.67-46.47 months] for the NDP group and 47.63 months (95% CI 45.13-49.07
      months) for the CBP group. Overall, there was no significant difference in PFS or
      OS between the two groups (P=0.09 for PFS, and P=0.65 for OS). For the patients
      with FIGO stage III-IV EOC, the NDP plus paclitaxel regimen significantly
      prolonged PFS (P=0.02) but did not result in improved OS (P=0.53) when compared
      with the CBP group. The patients in the NDP plus paclitaxel group also exhibited
      a lower incidence rate of grade 3 or 4 leucopenia (P=0.03). Other hematological
      and non-hematological toxicity profiles were similar between the two groups.
      Compared with CBP plus paclitaxel regimens, NDP plus paclitaxel regimens achieved
      comparable survival outcomes and similar toxicity profiles. However, patients of
      FIGO stage III-IV EOC may experience more clinical benefits from NDP plus
      paclitaxel treatment, including a prolonged PFS and a lower incidence rate of
      leucopenia. Therefore, an NDP-based regimen may be an alternative choice when
      using platinum-based agents to treat EOC.

PMID- 29467886
TI  - Primary intrapulmonary solitary fibrous tumours.
AB  - Due to the extreme rarity of primary intrapulmonary solitary fibrous tumours
      (SFTs), their clinical course, imaging characteristics, diagnosis, treatment and
      prognosis are poorly understood. The present study therefore assessed the
      diagnosis and management of primary intrapulmonary SFTs and systematically
      reviewed previously reported cases in the literature. A total of 5 patients who
      underwent resection for primary intrapulmonary SFTs were enrolled in the present
      study and their clinical course, tumour characteristics, management and survival
      were assessed in this retrospective study. Relevant studies regarding primary
      intrapulmonary SFTs were searched using PubMed and tumour characteristics,
      clinicopathologic features, therapeutic strategy and survival outcomes were
      reviewed. Of the 5 cases, all were males, with a mean age of 57.6 years (range,
      37-68 years). All patients were asymptomatic and were identified incidentally on
      routine computed tomography examination. A total of 3 patients underwent
      thoracotomy and 2 patients underwent video-assisted thoracoscopic surgery. All
      tumours were completely resected. Postoperative haemorrhage occurred in 1 patient
      and he received surgical intervention for haemostasis. The average hospital stay
      was 15 (4-22) days, and no mortality occurred. The mean length of the
      postoperative follow-up was 37.6 (1-67) months. One patient was lost to follow
      up, and 4 patients were asymptomatic. A total of 19 studies were identified from
      database searches. They included a total of 45 patients: Twenty-three males and
      22 females (mean age, 59.4 years; range, 7-81 years). A total of 12 patients were
      asymptomatic, and pain and coughing were the major symptoms. Five, one, two,
      four, and 17 tumours occurred in the right upper lobe, right middle lobe, right
      lower lobe, left upper lobe and left lower lobe, respectively. A total of 39
      patients underwent surgery, 1 patient underwent radiotherapy, and 1 patient
      underwent radiofrequency ablation. A total of 22 patients were followed up and
      the mean length of the postoperative follow-up was 48 (1-168) months. One patient
      was diagnosed with chest wall metastases, and 5 patients succumbed to mortality.
      To conclude, primary intrapulmonary SFTs are extremely rare and typically
      identified incidentally. The present findings indicated that the left lower lobe
      was the most common site location and complete surgical resection is a safe and
      effective treatment.

PMID- 29467887
TI  - Role and underlying mechanism of SPATA12 in oxidative damage.
AB  - Spermatogenesis-associated gene 12 (SPATA12) functions as an inhibitor in
      spermatogenesis and tumorigenesis. Our previous study demonstrated that SPATA12
      may be induced in tumor cells by ultraviolet (UV) C-mediated DNA damage,
      suggesting its importance in maintaining genomic integrity. In order to
      understand whether and how SPATA12 responds to oxidative damage, the present
      study established a cellular model of oxidative stress by detecting the effect of
      H2O2 on cell viability and intracellular superoxide dismutase activity, and the
      levels of glutathione and malondialdehyde (MDA). Quantitative polymerase chain
      reaction results demonstrated that H2O2 upregulated the expression of SPATA12,
      and a dual luciferase reporter gene assay indicated that transcription factor
      activator protein-1 (AP-1) was involved in the response of SPATA12 to oxidative
      stress. Through the exogenous expression of SPATA12, it was identified that
      SPATA12 decreased the level of reactive oxygen species and MDA, and also may
      reduce the degree of cellular oxidative damage and apoptosis induced by H2O2. In
      addition, resveratrol was demonstrated to increase the expression of SPATA12 by
      activating AP-1, and it may be used as a nontoxic activator of the SPATA12 gene.
      In conclusion, these results suggest that SPATA12 is upregulated by oxidative
      stress via AP-1, and that the exogenous expression of SPATA12 protects against
      H2O2-induced oxidative damage and apoptosis.

PMID- 29467888
TI  - Characteristics of breast metastases from non-breast solid tumors in 22 patients
      from a southern Chinese population.
AB  - Breast metastases from solid non-breast tumor types are rare; however, they
      should be always considered in the differential diagnosis of a breast lesion
      owing to the associated poor patient prognosis and the requirement of different
      therapeutic strategies compared with those used to treat primary breast cancer.
      The aim of the current study was to summarize the characteristics of metastases
      to the breast in a southern Chinese population. The medical records and
      pathological sections of 22 patients with pathologically confirmed extra-mammary
      metastases to the breast that presented to Sun Yat-sen University Cancer Center
      between January 2000 and December 2015 were retrospectively reviewed. The median
      age of onset for breast metastasis was 43 years (range, 10-62 years) and 19
      (86.4%) patients had a known history of a primary tumor. The mean interval from
      diagnosis of the primary tumor to breast metastasis was 16.5 months (range, 6-56
      months). A unilateral (45.5% left, 36.4% right), upper outer quadrant (15/22,
      68.2%) lesion of the breast was most frequently initially detected by self
      checking (63.6%). The most common origin of the primary tumor was the lung
      (22.7%). Nasopharyngeal carcinoma accounted for a high proportion of the
      metastases (18.2%). The median duration of survival from the time of diagnosis of
      a breast metastasis was 14 months (range, 2-74 months). A total of 10 patients
      (45.5%) succumbed to the disease. The results also indicated that overall
      survival in patients that underwent surgery was improved compared with patients
      who did not undergo surgery. The results of the present study demonstrated that
      clinical history, imaging findings, pathology from the primary tumor and
      immunostaining were required in combination to establish an accurate diagnosis.
      Further investigation into the improvement of the prognosis of patients with
      metastases to the breast following surgery is required.

PMID- 29467889
TI  - Serum immunoglobulin E response as a marker for unfavorable prognosis following
      cholesteryl pullulan-MAGE A4 vaccination.
AB  - Since 2009, a cancer vaccine clinical trial was conducted with melanoma antigen
      gene-A4 as an immunogenic agent. The levels of IgG1, IgG2 and IgG3, which are
      known to be Type 1 T helper cell-associated antibodies, and the levels of IgG4
      and IgE, which are known to be Type 2 T helper cell-associated antibodies, were
      measured and used as biomarkers for predicting therapeutic effect. The results of
      the present study indicated a strong positive correlation between IgG2 and IgG4,
      with a correlation coefficient of R=0.808 (P<0.0001). The survival time of
      patients in which IgE responses were induced was significantly shorter compared
      with the survival time of patients with no IgE induction. The results of the
      present study suggest that caution is required when antigen-specific IgE
      responses are induced during cancer vaccination therapy.

PMID- 29467890
TI  - Dosimetric comparison between IMRT and VMAT in irradiation for peripheral and
      central lung cancer.
AB  - The aim of the present study was to compare intensity-modulated radiation therapy
      (IMRT) and volumetric modulated arc therapy (VMAT) in irradiation of lung cancer.
      Plans of 14 patients were compared. The results demonstrated that in peripheral
      lung cancer, V5 (%) of the lung in partial-arc (PA)-VMAT was decreased compared
      with IMRT, single-arc (SA)-, and double partial-arc (2PA)-VMAT. V30 (%) of the
      lung in IMRT was decreased compared with SA-, PA- and 2PA-VMAT. In the case of
      planning target volume (PTV) not encompassing the mediastinum in central lung
      cancer, the conformality index (CI) and heterogeneity index (HI) of SA-VMAT was
      improved compared with IMRT, PA-, and 2PA-VMAT. The received dose of heart in SA
      VMAT was higher compared with IMRT, PA- and 2PA-VMAT. V30 (%) and V5 (%) of the
      lung in IMRT was higher compared with SA-, PA- and 2PA-VMAT; V10 (%) of the lung
      in 2PA was decreased compared with IMRT, SA- and PA. In the case of PTV
      encompassing the mediastinum in central lung cancer, the HI and CI of 2PA was
      improved compared with IMRT, SA- and PA-VMAT. The received dose of heart in 2PA
      was higher compared with IMRT, SA- and PA-VMAT. V30 (%) and V5 (%) of the lung in
      2PA-VMAT was higher compared with IMRT, SA- and PA-VMAT. V20 (%) of the lung in
      2PA was decreased compared with IMRT, SA- and PA-VMAT. In conclusion, it may be
      necessary to classify the radiotherapy plans of lung cancer into three categories
      including peripheral lung cancer, PTV not encompassing the mediastinum of central
      lung cancer, and PTV encompassing the mediastinum of central lung cancer. Each of
      IMRT, SA-VMAT, PA-VMAT, 2PA-VMAT strategy had individual advantages, and
      therefore it may be crucial to employ different planning techniques for different
      disease classifications and OAR requirements.

PMID- 29467891
TI  - Prognostic analysis of hepatocellular carcinoma on the background of liver
      cirrhosis via contrast-enhanced ultrasound and pathology.
AB  - The aim of this study was to analyze the correlation between the quantitative
      parameters of contrast-enhancement ultrasound for primary hepatocellular
      carcinoma (HCC) and biological manifestations of tumor (Ki-67), and to explore
      the related risk factors of primary hepatocellular carcinoma, so as to provide
      the theoretical basis for the further study on contrast-enhancement ultrasound
      manifestations, clinical features and prognosis of HCC. The patients with HCC
      confirmed by operation or puncture were collected, and those with the background
      of liver cirrhosis and immunohistochemical staining for tumor sample sections
      were selected. H&E staining sections of pathological tissues of tumor samples
      were observed, whether there was any microvessel invasion (MVI) was recorded, the
      microvessel density (MVD) was counted and the recurrence situations after liver
      cancer operation was followed up. The change in size of tumor at arterial phase
      in contrast-enhancement ultrasound, enhancement mode and form at arterial phase,
      and whether there were tortuous vessels inside or not, and the enhancement
      intensity, extinction time and extinction intensity at portal phase were
      observed. The relationship between the parameters of contrast-enhancement
      ultrasound and Ki-67, AFP, MVD, MVI, tissue differentiation degree of tumor
      samples and recurrence was analyzed. Under the background of liver cirrhosis,
      there were significant differences in different enhancement modes and
      quantification parameters of contrast-enhancement ultrasound for HCC with
      different expression of Ki-67. Those with obvious tumor enlargement,
      inhomogeneous enhancement at arterial phase and irregular enhancement form at
      arterial phase after contrast-enhancement ultrasound had a high incidence of
      positive Ki-67 and a high early recurrence rate. The inhomogeneous enhancement at
      arterial phase might predict the proliferative activity and recurrence time of
      tumor cells; irregular enhancement form at arterial phase might indicate tumor
      MVI; and the low enhancement of tumor at portal phase may predict a lower degree
      of tissue differentiation, a higher tumor malignancy and poor prognosis. The
      incidence of positive Ki-67 under the background of liver cirrhosis is high,
      indicating poor prognosis. The enhancement mode and parameters of contrast
      enhancement ultrasound for HCC may help evaluate the clinical biological
      manifestations of HCC and predict the postoperative recurrence of HCC.

PMID- 29467892
TI  - Transcription factor PU.1 is involved in the progression of glioma.
AB  - Glioma is a severe disease of the central nervous system. Although previous
      studies have identified the important role of the immune response in association
      with tumor intervention, it is still unknown whether PU.1, a transcription factor
      known for its role in myeloid differentiation and immune responses, is involved
      in the progression of glioma. In the present study, we found a significant
      increase in SPI1, the gene that encodes PU.1, in samples from patients with
      glioma. Through genotype-phenotype association analysis several candidate factors
      that may mediate the role of PU.1 in glioma were identified. To further validate
      the association between PU.1 and glioma we found that the expression of BTK, a
      potential target of PU.1, was also upregulated in patients with glioma. We also
      demonstrated that various biological pathways could be involved in PU.1
      associated glioma by analyzing these potential targets in the Reactome database.
      These results provide evidence that PU.1 could serve a role in the progress of
      glioma through its transcriptional targets in multiple signaling pathways.
      Therefore, in addition to its role in hematopoietic linage development and
      leukemia, PU.1 appears to be involved in the regulation of glioma and potentially
      in other malignant cancers.

PMID- 29467893
TI  - IFN-gamma induces the upregulation of RFXAP via inhibition of miR-212-3p in
      pancreatic cancer cells: A novel mechanism for IFN-gamma response.
AB  - Previous studies have demonstrated that pancreatic cancer-derived microRNA (miR)
      212-3p can inhibit the expression of regulatory factor X-associated protein
      (RFXAP), an important transcription factor for major histocompatibility complex
      (MHC) class II, and thereby lead to downregulation of MHC class II in dendritic
      cells. It has also been established that interferon (IFN)-gamma can increase the
      expression of MHC class II in immune cells. It was therefore hypothesized that
      IFN-gamma can inhibit miR-212-3p expression in pancreatic cancer, leading to the
      upregulation of RFXAP and MHC class II expression. This may represent a novel
      molecular mechanism underlying the use of IFN-gamma in immunotherapy. Data from
      the present study revealed that miR-212-3p was inhibited by IFN-gamma in a dose
      and time-dependent manner in the pancreatic ductal adenocarcinoma cell line PANC
      1. RFXAP and MHC class II expression were increased following IFN-gamma
      stimulation. A luciferase assay was performed to validate RFXAP as a target gene
      of miR-212-3p. The expression levels of RFXAP and MHC class II were decreased by
      miR-212-3p mimics and increased by miR-212-3p inhibitors. In PANC-1 cells
      transfected with miR-212-3p mimics, IFN-gamma stimulation could not increase the
      RFXAP and MHC class II. The results from the present study suggest that IFN-gamma
      increases RFXAP and MHC class II expression by inhibiting miR-212-3p. To the best
      of our knowledge, this is the first report of this novel molecular mechanism
      underlying the effects of IFN-gamma on pancreatic cancer, which may aid with the
      development of immunotherapies for patients with pancreatic cancer.

PMID- 29467894
TI  - Association between receptor interacting serine/threonine kinase 2 polymorphisms
      and gastric cancer susceptibility.
AB  - The present study aimed to investigate whether single nucleotide polymorphisms in
      receptor interacting serine/threonine kinase 2 (RIPK2), which encodes a component
      of the nucleotide binding oligomerization domain containing 2-RIP2 pathway, may
      compromise the innate immune response to Helicobacter pylori infection, leading
      to increased susceptibility to gastric cancer in the Japanese population. The
      present case control study investigated the associations between RIPK2 single
      nucleotide polymorphisms and gastric mucosal inflammation, atrophy and cancer
      susceptibility in 528 patients with gastric cancer and 697 patients without
      gastric malignancies on upper gastro-duodenal endoscopy. Overall, the RIPK2
      rs16900627 minor allele was significantly associated with the susceptibility to
      gastric cancer [OR, 1.37; 95% confidence interval (CI), 1.06-1.77; P=0.016],
      particularly of the intestinal type (OR, 1.53; 95% CI, 1.13-2.07; P=0.0062). It
      was also significantly associated with gastric mucosal atrophy (OR, 1.83; 95% CI,
      1.14-2.93; P=0.011). When assessing the severity of chronic gastritis using the
      updated Sydney system, the activity and inflammation scores, as well as atrophy
      and metaplasia scores, were significantly higher in rs16900627 minor allele
      carriers compared with wild-type homozygotes. In patients younger than 60 years
      old, the pepsinogen I/II ratio was significantly lower in rs16900627 minor allele
      carriers compared with wild-type homozygotes (P=0.037). The rs16900627 minor
      allele is associated with the severity of gastric mucosal inflammation and the
      development of gastric mucosal atrophy. Carriers of this allele may have an
      increased risk for the development of gastric cancer, particularly of the
      intestinal type.

PMID- 29467895
TI  - Clinicopathological and functional implications of the inhibitor of apoptosis
      proteins survivin and XIAP in esophageal cancer.
AB  - Based on their overexpression and important roles in progression and therapy
      resistance in malignant diseases, the inhibitor of apoptosis protein family (IAP)
      members, survivin and X-linked inhibitor of apoptosis protein (XIAP), represent
      attractive candidates for targeted therapy. The present study investigated the
      prognostic and biological relevance of survivin and XIAP in esophageal squamous
      cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Survivin and XIAP
      expression was analyzed by immunohistochemistry using tissue microarrays
      containing 120 ESCC and 90 EAC samples as well as the corresponding non
      neoplastic esophageal mucosa samples. IAP expression levels were then correlated
      to clinicopathological parameters and overall survival to identify any
      associations. In addition, esophageal cancer cell lines were treated with the
      survivin inhibitor YM155, and the XIAP inhibitors Birinapant and GDC-0152 in
      vitro. Survivin and XIAP expression were significantly increased in EAC and ESCC
      when compared with tumor-adjacent mucosa. In patients with ESCC XIAP expression
      was associated with female gender and advanced tumor stages, and nuclear survivin
      expression was associated with poor grading. High XIAP expression was identified
      as an independent negative prognostic marker in ESCC. By contrast, XIAP
      inhibitors did not affect cancer cell viability in vitro, and the small molecule
      survivin inhibitor YM155 significantly reduced cell viability and proliferation
      in esophageal cancer cell lines. Western blot analysis revealed a dose dependent
      decrease of survivin accompanied by an increased poly (adenosine diphosphate
      ribose) polymerase cleavage following YM155 treatment. These findings underline
      the potential role of survivin and XIAP in the oncogenesis of esophageal cancer
      and provide a rationale for future clinical studies investigating the therapeutic
      efficacy of IAP directed therapies in patients with esophageal cancer.

PMID- 29467896
TI  - 17beta-estradiol regulates the malignancy of cancer stem-like cells derived from
      the MCF7 cell line partially through Sox2.
AB  - As a major common malignant tumor in women, the malignant behavior of breast
      cancer, which includes tumorigenesis and metastasis, is associated with estrogen,
      particularly 17beta-estradiol (E2). With accumulating evidence demonstrating that
      cancer stem-like cells (CSCs) serve a function in the malignant behavior of
      breast cancer, including metastasis, recurrence and chemoresistance, the effects
      of E2 on the physiological processes of CSCs have been attracting more attention.
      In the present study, in order to investigate the effects of E2 on CSCs, CSCs
      from the MCF7 breast cancer cell line were isolated and treated with 1, 10 and 50
      nM E2. Detection of cell proliferation following E2 treatment revealed that 10 nM
      E2 treatment inhibited cell proliferation, whereas 50 nM E2 treatment resulted in
      the induction of apoptosis on CSCs. In order to further investigate the effects
      of E2 treatment on migration, colony formation and the self-renewal capacity of
      CSCs in vitro, cells were treated with 1 and 10 nM E2. As expected, compared with
      mock group, the self-renewal capacity of the CSCs was slightly increased by 10 nM
      E2 treatment, while 1 nM exhibited no observable effect. E2 treatment
      demonstrated different effects on the proliferation, migration, colony formation
      and self-renewal capacity of CSCs in a dose-dependent manner.

PMID- 29467897
TI  - Prognostic significance of c-Met, beta-catenin and FAK in patients with
      hepatocellular carcinoma following surgery.
AB  - The present study aimed to investigate the prognostic value of specific molecular
      markers in patients with hepatocellular carcinoma (HCC) who had received surgery.
      Immunohistochemical analysis was used to measure the expression of hepatocyte
      growth factor receptor (c-Met), beta-catenin and focal adhesion kinase (FAK) in
      patients with HCC. c-Met expression was identified to be high in patients with
      larger tumors, higher alpha-fetoprotein (AFP) levels, higher Edmondson grades,
      portal vein invasion and higher tumor-node-metastasis (TNM) stages. FAK
      expression was high in patients with portal vein invasion, higher Edmondson
      grades and higher TNM stages. beta-catenin expression was high in patients with
      larger tumors, hepatitis B virus (HBV) infection, portal vein invasion, higher
      Edmondson grades and higher TNM stages. Following multivariate analysis, FAK
      (P=0.002) and beta-catenin (P=0.006) expression levels were demonstrated to be
      significantly associated with Edmondson grade. Additionally, the tumor size
      (P=0.009) and HBV infection status (P=0.002) were revealed to be associated with
      beta-catenin expression. Kaplan-Meier survival curve analysis demonstrated that
      patients with HCC with higher FAK expression, higher beta-catenin expression,
      portal vein invasion, higher Edmondson grades, higher TNM stages, younger ages
      and higher AFP levels had significantly poorer prognoses. Cox's regression
      analysis revealed that the survival period was correlated with the Edmondson
      grade, age, AFP level, and FAK and beta-catenin expression. Univariate analysis
      of c-Met, beta-catenin and FAK identified a significant correlation between FAK
      and beta-catenin (P=0.015). Correlation analysis revealed no significant
      correlation between the three molecular markers, but beta-catenin and c-Met were
      markedly correlated (P=0.052). No significant correlation between FAK, c-Met or
      beta-catenin expression was identified. FAK and beta-catenin expression
      demonstrated a correlation with a range of clinicopathological factors, and high
      FAK and beta-catenin expression levels were identified to be correlated with a
      poor survival rate of patients with HCC. Thus, patients with higher FAK and beta
      catenin expression may require more aggressive therapy. The results of the
      present study suggest that FAK and beta-catenin expression possess more
      prognostic value than c-Met expression in patients with HCC.

PMID- 29467898
TI  - Anticancer effect of miR-96 inhibitor in bladder cancer cell lines.
AB  - The present study aimed to investigate the role of microRNA-96 (miR-96) in the
      proliferation, invasion and apoptosis of bladder cancer cell lines, and the
      associated mechanisms. The expression of miR-96 and human ether-a-go-go-related
      (HERG1) potassium channel in the normal uroepithelium SV-HUC-1 cell line, and
      bladder cancer T24 and 5637 cell lines were examined using reverse transcription
      polymerase chain reaction or/and western blotting. Transfection with miR-96
      inhibitor or scrambled control (SC) was used to study the biological activities
      of miR-96 in bladder cancer cell lines. MTT, flow cytometric and Transwell assays
      were applied to detect cell viability, apoptosis and invasion, respectively. A
      dual-luciferase reporter assay was applied to determine the association between
      miR-96 and HERG1 expression. As demonstrated, miR-96 was highly expressed in the
      two bladder cancer cell lines, particularly in T24 cells. Following transfection
      with miR-96 inhibitor, miR-96 expression was significantly reduced in the T24
      cell line, compared with SC. The miR-96 inhibitor suppressed cell proliferation
      and invasion, promoted apoptosis and arrested the cell cycle at the G1 phase.
      Consistently, HERG1 was also highly expressed in the two bladder cancer cell
      lines at the mRNA and protein level, but not in the normal uroepithelium cell
      line. The miR-96 inhibitor also significantly decreased HERG1 expression compared
      with SC. The results of the dual-luciferase reporter assay indicated that miR-96
      directly targeted wild-type HERG1. In conclusion, miR-96 inhibitor exhibited
      anticancer effects on bladder cancer cells by inhibiting proliferation and
      invasion of cells, and promoting their apoptosis. HERG1 was an important target
      of miR-96. These results provided experimental evidence supporting miR-96 as a
      therapeutic target for patients with bladder cancer.

PMID- 29467899
TI  - TNF-alpha promotes colon cancer cell migration and invasion by upregulating TROP
      2.
AB  - High levels of tumor-associated calcium signal transduction protein (TROP)-2 have
      been demonstrated to be strongly associated with tumor necrosis factor (TNF)
      alpha levels in colon cancer. In the present study, the effect of TNF-alpha on
      the regulation of TROP-2 expression and its effect in colon cancer cell migration
      and invasion were investigated in vitro. TROP-2 protein levels were evaluated in
      HCT-116 human colon cancer cells cultured with various concentrations of TNF
      alpha using western blot analysis. Changes in the migratory and invasive
      potential of the cells were evaluated using a wound healing and transwell assay,
      respectively. Then, TROP-2 expression was downregulated in cells by use of siRNA,
      and TROP-2 knockdown was confirmed at the mRNA and protein level by reverse
      transcription-quantitative polymerase chain reaction and western blotting,
      respectively. The migration and invasion potential of cells transfected with TROP
      2 siRNA was also evaluated. Levels of several mitogen-activated protein kinase
      proteins, namely p38, c-Jun N-terminal kinase (JNK) and extracellular signal
      regulated kinase (ERK), were detected in cells treated with TNF-alpha using
      western blot analysis. The results demonstrated that TROP-2 protein levels
      increased in cells treated with lower concentrations of TNF-alpha, but decreased
      in cells treated with higher concentrations of TNF-alpha, compared with untreated
      control. Maximum TROP-2 levels were observed in cells treated with 20 ug/l TNF
      alpha. Migration and invasion were enhanced in cells treated with 20 ug/l TNF
      alpha. When TROP-2 was silenced in colon cancer cells by siRNA, migration and
      invasion were significantly decreased compared with control cells. TNF-alpha
      stimulation activated the ERK1/2 pathway, but did not significantly affect p38
      and JNK phosphorylation levels. Treatment with a specific ERK1/2 inhibitor
      suppressed the TNF-alpha-induced upregulation of TROP-2 and the TNF-alpha-induced
      colon cancer cell migration and invasion. In conclusion, the present results
      demonstrated that low concentrations of TNF-alpha significantly enhanced colon
      cancer cell migration and invasion by upregulating TROP-2 via the ERK1/2
      signaling pathway.

PMID- 29467900
TI  - Overexpression of RHEB is associated with metastasis and poor prognosis in
      hepatocellular carcinoma.
AB  - Aberrant expression of Ras homolog enriched in brain (RHEB) has been observed in
      a variety of cancer tissues and is closely associated with clinicopathological
      features. However, the expression profile of RHEB in patients with hepatocellular
      carcinoma (HCC) and its clinical signature with underlying mechanisms have not
      been explored thus far. To analyze the association between RHEB expression and
      clinicopathological features, the RHEB expression levels were determined in the
      present study using gene microarrays, immunohistochemistry and western blotting
      in 60 liver cancer tissues and 35 normal liver tissues. Downregulation of RHEB
      expression in liver cancer cell lines was achieved by RNA interfering technology
      to explore its biological function in HCC. RHEB expression was high in liver
      cancer tissues, with an increase of 2.00+/-0.19-fold compared with normal tissues
      and of 2.00+/-0.27-fold compared with adjacent non-cancer tissues. RHEB
      expression increased along with the clinical staging of HCC, and the overall
      survival and mortality of patients were closely correlated to RHEB levels, micro
      vascular invasion, hepatitis B virus-DNA titer, tumor differentiation and
      pathological satellites (P<0.05). After knocking down RHEB in SMMC-7721 cells,
      the growth of liver cancer cells was significantly reduced. The majority of cells
      were blocked in S-phase, and their colony-forming and proliferating abilities
      significantly decreased (P<0.05). In vivo, upon downregulation of RHEB
      expression, the tumorigenic ability of HCC significantly decreased (P<0.05).
      These data suggest that RHEB expression is a significant prognostic factor and
      may be important in HCC cell growth. The present study highlights the importance
      of RHEB as a novel prognostic marker of HCC.

PMID- 29467902
TI  - Remodeling and spacing factor 1 overexpression is associated with poor prognosis
      in renal cell carcinoma.
AB  - The present study aimed to assess the expression and prognostic significance of
      remodeling and spacing factor 1 (RSF1; HBXAP) in renal cell carcinoma (RCC). RSF1
      expression was analyzed using immunohistochemistry on tissue samples from a
      consecutive series of 137 patients with RCC who underwent tumor resection between
      November 2000 and March 2004. The associations between RSF1 expression,
      clinicopathological factors and patient survival were investigated.
      Immunohistochemistry revealed that RSF1 was highly expressed in 43.1% (59/137) of
      the RCC samples. RSF1 expression levels were associated with the T stage of the
      Tumor-Node-Metastasis grading system. Kaplan-Meier survival analysis indicated
      that high RSF1 expression in RCC was significantly associated with a poor
      prognosis. Multivariate analysis revealed that RSF1 expression is an independent
      prognostic parameter for the duration of overall survival of patients with RCC.
      The results demonstrated that a high expression level of RSF1 in RCC is
      associated with advanced tumor stages and a poor prognosis. To the best of our
      knowledge, the present study provides novel evidence of the biological
      significance of RSF1 expression in RCC.

PMID- 29467901
TI  - Ubiquitin-specific protease 15 promotes tumor cell invasion and proliferation in
      glioblastoma.
AB  - Glioblastoma multiforme (GBM) is one of the most aggressive types of brain tumor
      worldwide. Despite the advances made in treatment and research, the median
      survival time for GBM patients remains <1.5 years, providing impetus for the
      identification of potential novel therapeutic target genes to improve GBM
      treatment. The deubiquitinating enzyme ubiquitin specific peptidase 15 (USP15)
      has emerged as a pro-oncogenic factor; however, its function in GBM has yet to be
      fully elucidated. The present study sought to determine whether or not USP15 is
      implicated in GBM cell invasion and proliferation. Following the depletion of
      USP15 in U87-MG and U251-MG cells by lentivirus-mediated USP15 short hairpin RNA
      (shRNA), the invasiveness of glioma cells was investigated. The results of the
      present study demonstrated that glioma cells expressing USP15 shRNA exhibited
      significantly lower invasiveness than cells that did not express USP15 shRNA.
      Additionally, USP15 depletion led to the upregulation of E-cadherin and
      downregulation of the mesenchymal markers, N-cadherin and vimentin. Furthermore,
      the influence of USP15 on glioma cell proliferation was investigated and
      depletion of USP15 resulted in a marked reduction in cell proliferation. Taken
      together, the findings of the present study clearly support the hypothesis that
      USP15 renders GBM cells capable of invasion and proliferation.

PMID- 29467903
TI  - Effect of selective inhibition of aquaporin 1 on chemotherapy sensitivity of J82
      human bladder cancer cells.
AB  - The occurrence of resistance to mitomycin C (MMC) often limits its clinical
      effectiveness. Combination therapy thus is employed to overcome this treatment
      resistance. The present study aimed to establish a novel J82 bladder cancer cell
      line so as to study the effect of inhibition of aquaporin 1 (AQP-1) on
      chemotherapy sensitivity of J82 bladder cancer cells. A novel J82 bladder cancer
      cell line whose expression of AQP-1 is inhibited was established through
      transfection of J82 cells with newly constructed recombinant plasmid. The
      resulting cell line was designated J82-short hairpin (sh)AQP1 and was subjected
      to further analyses together with J82 cell line. Reverse transcription-polymerase
      chain reaction was used to quantify the expression of AQP-1mRNA in the cells;
      cell viability was analyzed with MTT assay and apoptosis was measured by flow
      cytometry. The expression of cell proliferation and cell apoptosis-associated
      proteins, proliferating cell nuclear antigen (PCNA), B cell lymphoma 2 (Bcl-2),
      Bcl-2 associated X protein (Bax) and caspase-3, were detected by Western blot. A
      statistically significant decrease in the transcription and expression of AQP1
      was observed in the J82-shAQP1 cells as compared with J82 cells. J82-shAQP1 cells
      treated by MMC, also had a lower cell viability than J82 cells treated by MMC and
      showed enhanced apoptosis. Western blot analysis revealed J82-shAQP1 cells
      treated by MMC had less expression of PCNA, lower bcl-2/Bax ratio and more
      expression of caspase-3 as compared with the J82 cells treated by MMC. Selective
      inhibition of AQP-1 enhanced MMC chemotherapy sensitivity of J82 bladder cancer
      cells, suggesting combination of AQP-1 inhibition with MMC treatment as a
      promising treatment strategy to overcome bladder cancer treatment resistance.

PMID- 29467904
TI  - Human sodium iodide transporter gene-mediated imaging and therapy of mouse
      glioma, comparison between 188Re and 131I.
AB  - Novel treatment options are urgently required for patients with glioma who are
      not effectively treated through standard therapy. Human sodium iodide symporter
      (hNIS) is a molecular target of certain tumors types. Compared with 131I, 188Re
      possesses a higher energy and shorter half-life; therefore, the effects of 188Re
      and 131I were compared in hNIS-mediated gene imaging and therapy in the present
      study. Recombinant human brain glioma cell line U87 was transfected with a
      recombinant lentiviral vector containing hNIS (U87-hNIS). U87-0 cell line
      transfected with blank lentivirus was prepared as a control. In vitro, the 188Re
      and 131I uptake of U87-hNIS cells were 21.3-times and 25.9-times that of the
      control groups, however the excretion rate of the two nuclides was very rapid,
      and the half-life was only ~4 min. Sodium perchlorate inhibited hNIS-mediated
      188Re and 131I uptake to levels observed in the control groups. 188Re and 131I
      were able to kill U87-hNIS cells selectively, with a survival of only 21.6 and
      36.2%, respectively. U87-hNIS nude mice appeared to accumulate 188Re, with a
      ratio of radioactivity counts between tumor and non-tumor sites of ~13.5 compared
      with 10.3 of 131I 1 h after radionuclide injection. In contrast with in vitro
      studies, U87-hNIS cells demonstrated a notable increase in 188Re retention in
      vivo, even 24 h after 188Re injection. U87-hNIS cells also exhibited increased
      131I retention in vivo; however, as the time increased, 131I was rapidly released
      with the tumor no longer able to be imaged 24 h after 131I injection. Following
      treatment, U87-hNIS tumors experienced a volume reduction of 24.1%, whereas U87-0
      cells demonstrated an increase of 28.8%. 188Re and 131I were revealed to be
      effective at decreasing tumor volume compared with the control. However, 188Re
      was significantly more potent compared with 131I (P<0.01). The present study
      indicated that the U87-hNIS cell line is sufficient to induce specific 188Re and
      131I uptake, which may kill cells in vitro and in vivo. 188Re exhibited an
      increased retention time in vivo compared with 131I, which facilitates the
      imaging and therapy of U87-hNIS tumors.

PMID- 29467905
TI  - [18F]FDG-PET/CT and MRI for initial pelvic lymph node staging in patients with
      cervical carcinoma: The potential usefulness of [18F]FDG-PET/MRI.
AB  - The current study aimed to determine the optimum diagnostic imaging technique out
      of magnetic resonance imaging (MRI), 18F-fludeoxyglucose positron emission
      tomography/computed tomography ([18F]FDG-PET/CT, otherwise known as PET/CT) and
      [18F]FDG-PET/MRI (otherwise known as PET/MRI) for the pelvic lymph node staging
      (N-staging) of untreated cervical carcinoma (CC). A total of 27 patients were
      included in the present study. All patients had undergone pre-treatment with
      PET/CT and MRI <=45 days prior to undergoing a lymphadenectomy. The results from
      PET (separated from PET/CT), MRI and the statistically combined results of
      (virtual) PET/MRI were compared to those from histological analyses (the gold
      standard). A per-patient-based analysis of the detection of pelvic lymph node
      metastases indicated that PET/MRI had a sensitivity of 64%. The specificity of
      PET/CT and MRI were 69 and 62%, respectively. The positive predictive value (PPV)
      was 69 and 64% for PET/CT and MRI, respectively. The negative predictive value
      (NPV) was 64 and 62% for PET/CT and MRI, respectively. The sensitivity of the PET
      guided PET/MRI and the MRI-guided PET/MRI was 64% for both. The specificity of
      the PET-guided PET/MRI and the MRI-guided PET/MRI was 77 and 62%, respectively.
      The PPV was 75% for PET-guided PET/MRI and 64% for MRI-guided PET/MRI, and the
      NPV was 67 and 62%, respectively. PET/CT and the virtual PET/MRI exhibited the
      same low sensitivity (64%). PET/MRI exhibited slightly better results than PET/CT
      regarding specificity (77 vs. 69%, respectively), PPV (75 vs. 69%, respectively)
      and NPV (67 vs. 64%, respectively). The results of the present study suggested
      that PET/CT and MRI are not optimal diagnostic modalities, and that PET/MRI does
      not necessarily lead to better results than PET/CT, in the pelvic N-staging of
      CC.

PMID- 29467906
TI  - beta-elemene enhances anticancer and anti-metastatic effects of osteosarcoma of
      ligustrazine in vitro and in vivo.
AB  - The present study aimed to determine the anticancer effects of the combination of
      beta-elemene and ligustrazine in vitro as well as in in vivo. Following
      evaluation using an MTT assay, beta-elemene, ligustrazine and the beta-elemene
      ligustrazine combination treatments all exhibited the capacity to inhibit the
      growth of OS-732 cells, with inhibitory rates of 43.3, 54.4, and 75.0%,
      respectively. Using a flow cytometry assay, it was determined that the beta
      elemene-ligustrazine combination possessed the highest apoptotic rate (30.6%).
      Furthermore, beta-elemene-ligustrazine combination treatment resulted in the
      highest downregulation of G protein-coupled receptor 124, vascular endothelial
      growth factor, matrix metallopeptidase (MMP)-2 and MMP-9 mRNA, and protein
      expression levels. In addition, the combined treatment led to an increase in the
      mRNA and protein expression of endostatin, TIMP metallopeptidase inhibitor (TIMP)
      1 and TIMP-2 in OS-732 cells. Additionally, beta-elemene-ligustrazine caused a
      decrease in nuclear factor-kappaB, interleukin-8, C-X-C motif chemokine receptor
      4 and urokinase-type plasminogen activator mRNA expression, as well as an
      increase in caspase-3, caspase-8, and caspase-9 mRNA expression. In vivo, the
      beta-elemene-ligustrazine combination was able to reduce the weight and the bulk
      of the tumor in BALB/c-nu/nu nude mice compared with any other group. All the
      results described above regarding changes to mRNA and protein expression were
      further confirmed in vivo in the tumor tissue of mice. The results of the present
      study have suggested that the combination of beta-elemene-ligustrazine exhibits
      greater anticancer effects compared with beta-elemene- or ligustrazine-alone
      treatment.

PMID- 29467907
TI  - TGFBR1*6A is a potential modifier of migration and invasion in colorectal cancer
      cells.
AB  - Type 1 transforming growth factor beta receptor (TGFBR1)*6A, a common hypomorphic
      variant of TGFBR1, may act as a susceptibility allele in colorectal cancer.
      However, the contribution of TGFBR1*6A to colorectal cancer development is
      largely unknown. To test the hypothesis that TGFBR1*6A promotes colorectal cancer
      invasion and metastasis via Smad-independent transforming growth factor-beta (TGF
      beta) signaling, the effect of TGFBR1*6A on the invasion of colorectal cancer
      cells was assessed. pCMV5-TGFBR1*6A-HA plasmids were transfected into SW48 and
      DLD-1 cells by Lipofectamine-mediated DNA transfection. The effect of TGF-beta1
      on the proliferation of SW48 and DLD-1 cells transfected with TGFBR1*6A was
      determined by MTT assay. The effects of the TGF-beta1 on the invasion of the
      transfected SW48 and DLD-1 cells were determined using Matrigel-coated plates.
      Transforming migrating chambers were used to determine the effects of TGF-beta1
      on the migration of the transfected SW48 and DLD-1 cells. Western blot analysis
      was used to determine the expression of phosphorylated (p-) extracellular-signal
      regulated kinase (ERK), p-P38 and p-SMAD family member 2 in SW48 cells. Using
      transfected TGFBR1*6A SW48 and DLD-1 cell lines our group demonstrated that, in
      comparison with TGFBR1*9A, TGFBR1*6A is capable of switching TGF-beta1 growth
      inhibitory signals into growth-stimulatory signals which significantly increased
      the invasion of SW48 and DLD-1 cells. Functional assays indicated that TGFBR1*6A
      weakened Smad-signaling but increased ERK and p38 signaling, which are crucial
      mediators of cell migration and invasion. From this, it was possible to conclude
      that TGFBR1*6A enhanced SW48 cell migration and invasion through the mitogen
      activated protein kinase pathway and that it may contribute to colorectal cancer
      progression in a TGF-beta1/Smad signaling-independent manner. This suggests that
      TGFBR1*6A may possess oncogenic properties and that it may affect the migration
      and invasion of colorectal cancer cells.

PMID- 29467908
TI  - Long non-coding RNA SPRY4-IT1 promotes the proliferation and invasion of U251
      cells through upregulation of SKA2.
AB  - The long non-coding RNA SPRY4-intronic transcript 1 (SPRY4-IT1) has been shown to
      promote the progression of cancer; however, the role of SPRY4-IT1 in glioma
      remains unclear. The present study demonstrated that SPRY4-IT1 expression was
      markedly increased in glioma tissues and cells compared with normal brain
      tissues, whereas knockdown of SPRY4-IT1 inhibited cell proliferation, migration,
      and invasion in U251 cells. Spindle and kinetochore associated complex subunit 2
      (SKA2) was found to be a target of SPRY4-IT1 and was downregulated by SPRY4-IT1
      knockdown. Additionally, SPRY4-IT1 expression was positively correlated with SKA2
      in glioma tissues. To the best of our knowledge, the present study provides the
      first demonstration that SKA2 may have an oncogenic role in U251 cells. These
      results indicate that SPRY4-IT1 may serve a notable role in the molecular
      etiology of glioma and represents a potential target in glioma therapy.

PMID- 29467909
TI  - Apoptosis-sensitizing activity of birinapant in head and neck squamous cell
      carcinoma cell lines.
AB  - Inhibitor of apoptosis proteins, which are overexpressed in head and neck
      squamous cell carcinoma (HNSCC), may cause therapeutic resistance. Using SMAC
      mimetic compounds, including birinapant, to degrade and/or inhibit these proteins
      and sensitize apoptosis may enhance therapies in HNSCC. Fas expression was
      analyzed in nine HNSCC cell lines and one keratinocyte cell line via flow
      cytometry. These cell lines were treated with Fas ligand-Fc (FasL) and
      birinapant, a bivalent SMAC mimetic, in mono and combination therapies.
      Cytotoxicity was measured using a crystal violet assay. Annexin V assay was
      performed for detection of apoptosis. The treatment efficacy of mono and
      combination therapies was statistically analyzed. Nonlinear regression analysis
      was performed to determine the inhibitory concentration (IC10) of birinapant. Fas
      expression was detected in each cell line tested. Mono treatment with FasL
      revealed minor to no apoptotic effects in the majority of the cell lines. Crystal
      violet and Annexin V staining revealed increased apoptosis rates for all cell
      lines following incubation with birinapant in mono treatment. Combination
      treatment with FasL and birinapant (IC10) revealed additional and synergistic
      effects in eight out of the ten cell lines. To the best of our knowledge, the
      present study provided the first evidence of the apoptosis-sensitizing activity
      of combination treatment with FasL and birinapant in HNSCC cell lines.

PMID- 29467910
TI  - Predictive value of inflammatory indexes on the chemotherapeutic response in
      patients with unresectable lung cancer: A retrospective study.
AB  - Chemotherapy is widely administered to patients with advanced lung cancer;
      however, data regarding chemotherapeutic sensitivity are limited. The present
      study aimed to investigate the predictive value of inflammatory indexes for
      chemotherapeutic efficacy in advanced lung cancer. Patients with stage III and IV
      unresectable lung cancer that were treated with first-line chemotherapy between
      January 2007 and December 2011 were retrospectively identified, and
      chemotherapeutic response was evaluated following 2 or 3 chemotherapy cycles.
      Prior to chemotherapy, hematologic data and clinicopathological parameters were
      collected using electronic medical records. The associations between the main
      inflammatory indexes [which included the pretreatment neutrophil count (PNC),
      neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR)] and the
      chemotherapeutic efficacy, as well as the prognostic value of the indexes, were
      analyzed. According to the receiver operating characteristic curve, PLR failed to
      reach diagnostic accuracy for overall chemotherapeutic response. PNC and NLR were
      each classified into two groups according to the cut-off values (4.635*109/l for
      PNC and 2.443 *109/l for NLR). The overall response rate was significantly higher
      in the low PNC [odds ratio, 3.261; 95% confidence interval (CI), 2.102-5.060;
      P<0.001, vs. high PNC] and low NLR groups (odds ratio, 1.596; 95% CI, 1.037
      2.454; P=0.033, vs. high NLR). Univariate analyses showed that the high PNC (HR,
      1.487) and high NLR groups (HR, 1.288) were associated with poor progression-free
      survival (PFS); however, NLR was considered statistically insignificant in
      multivariate analysis. In summary, high PNC and NLR values are associated with
      chemoresistance and an unfavorable prognosis, with the present study
      demonstrating that PNC has increased sensitivity when compared with other
      inflammatory indexes in predicting chemotherapeutic efficacy. Therefore, PNC has
      the potential to be used as a reliable and suitable predictor to stratify a high
      risk of chemoresistance in patients with stage III and IV unresectable lung
      cancer.

PMID- 29467911
TI  - Downregulation of the long non-coding RNA taurine-upregulated gene 1 inhibits
      glioma cell proliferation and invasion and promotes apoptosis.
AB  - Expression of the long non-coding RNA taurine-upregulated gene 1 (TUG1) is
      associated with various aggressive tumors. The present study aimed to investigate
      the biological function of TUG1 in regulating apoptosis, proliferation, invasion
      and cell cycle distribution in human glioma U251 cells. Lentivirus-mediated TUG1
      specific microRNA was transfected into U251 cells to abrogate the expression of
      TUG1. Flow cytometry analysis was used to examine the cell cycle distribution and
      apoptosis of U251 cells. Cellular proliferation was examined using Cell Counting
      Kit-8 (CCK-8) assays and invasion was examined by Transwell assays. The apoptotic
      rate of cells in the TUG1-knockdown group was significantly higher than in the
      negative control (NC) group (11.58 vs. 9.14%, P<0.01). CCK-8 assay data
      demonstrated that the proliferative ability of cells within the TUG1-knockdown
      group was lower compared with that of the NC group. A Transwell invasion assay
      was performed, which revealed that the number of invaded cells from the TUG1
      knockdown group was the less compared with that of the NC group. In addition, the
      G0/G1 phase population was significantly increased within the treated group
      (44.85 vs. 38.45%, P<0.01), as measured by flow cytometry. The present study
      demonstrated that the downregulation of TUG1 may inhibit proliferation and
      invasion, and promote glioma U251 cell apoptosis. In addition, knockdown of TUG1
      may have an effect on cell cycle arrest. The data presented in the current study
      indicated that TUG1 may be a novel therapeutic target for glioma.

PMID- 29467912
TI  - pi-Electron systems containing Si=Si double bonds.
AB  - Sterically large substituents can provide kinetic stabilization to various types
      of low-coordinate compounds. For example, regarding the chemistry of the group 14
      elements, since West et al. introduced the concept of kinetic protection of the
      otherwise highly reactive Si=Si double bond by bulky mesityl (2,4,6
      trimethylphenyl) groups in 1981, a number of unsaturated compounds of silicon and
      its group homologs have been successfully isolated by steric effects using the
      appropriate large substituents. However, the functions and applications of the Si
      Si pi-bonds consisting of the 3ppi electrons on the formally sp2-hybridized
      silicon atoms have rarely been explored until 10 years ago, when Scheschkewitz
      and Tamao independently reported the model systems of the oligo(p
      phenylenedisilenylene)s (Si-OPVs) in 2007. This review focuses on the recent
      advances in the chemistry of pi-electron systems containing Si=Si double bonds,
      mainly published in the last decade. The synthesis, characterization, and
      potential application of a variety of donor-free pi-conjugated disilene compounds
      are described.

PMID- 29467913
TI  - Oncoplastic Reduction Pattern Technique Following Removal of Giant Fibroadenoma.
AB  - Objective: Oncoplastic surgery was developed to allow for large tumor excision
      and immediate breast reconstruction with the goal of optimal breast shape and
      symmetry. Although initially used in women who underwent lumpectomy for breast
      malignancy, these techniques can be useful for cosmetic issues caused by benign
      breast disease. We describe a modification of an inferior pedicle with Wise
      pattern reduction mammoplasty for oncoplastic reconstruction of a giant
      fibroadenoma. Methods: A 30-year-old woman with size 32 DD breasts was referred
      by the surgical oncologist with a biopsy-proven fibroadenoma of the right breast.
      Surgical oncology excised the mass, and immediate reconstruction was performed
      with an inferolateral pedicle Wise-pattern reduction technique. Results:
      Immediately postoperatively, the patient showed excellent symmetry. Follow-up
      postoperatively showed good wound healing, preserved symmetry, and a viable,
      sensate nipple. Conclusions: Oncoplastic breast reconstruction in a reduction
      pattern technique after giant fibroadenoma removal provides an excellent outcome,
      allowing for improved symmetry.

PMID- 29467914
TI  - Comprehensive Review and Case Study on the Management of Buried Penis Syndrome
      and Related Panniculectomy.
AB  - Objective: This paper discusses the various surgical techniques and outcomes
      associated with management of buried penis syndrome. Methods: Presented is the
      case of a 49-year-old man with morbid obesity, leading to massive panniculus and
      buried penis. We review our technique for reconstruction of the buried penis and
      treatment of the overlying large panniculus. Literature search was conducted to
      review current techniques in correcting buried penis syndrome. Results: The
      patient underwent a successful panniculectomy with removal of all excess skin and
      tissue. Thoughtful planning and coordination between plastic surgery and urology
      were paramount to externalize the penis for an excellent functional and cosmetic
      result. Conclusions: Management of a buried, hidden penis is complex and
      difficult. Patients are often obese and have poor hygiene due to the inability to
      cleanse areas that are entrapped by excessive fat. Following removal of the
      overhanging panniculus, satisfactory reconstruction of a hidden penis is possible
      when proper care is taken to adhere the base of the penis to the pubis. Split
      thickness skin grafts are often necessary but depend on the viability of the
      penile skin and whether it is restricting penile length. Complications with wound
      dehiscence and infection are not uncommon; however, patients generally recover
      well, are satisfied with results, and are reported to have fully regained urinary
      and sexual functions following surgical correction of the buried penis.

PMID- 29467915
TI  - Correction to: Neisseria lactamica Y92-1009 complete genome sequence.
AB  - [This corrects the article DOI: 10.1186/s40793-017-0250-6.].

PMID- 29467916
TI  - Utility of endoscopic ultrasound and endoscopy in diagnosis and management of
      hepatocellular carcinoma and its complications: What does endoscopic
      ultrasonography offer above and beyond conventional cross-sectional imaging?
AB  - Hepatocellular carcinoma constitutes over 90% of the primary liver tumors, the
      rest being cholangiocarcinoma. It has an insidious presentation, which is
      responsible for the delayed presentation. Hence, the management strategy relies
      on screening to diagnose it an early stage for curative resection and/or
      treatment with local ablative techniques or chemotherapy. However, even with
      different screening programs, more than 60% of tumors are still detected at an
      advanced stage, leading to an unchanged mortality rate, thereby implying a room
      for improvement in the screening and diagnostic process. In the last few years,
      there has been evolution of utility of endoscopy, specifically endoscopic
      ultrasonography along with Fine needle aspiration, for this purpose, which we
      comprehensively review in this article.

PMID- 29467917
TI  - Preliminary study of automatic gastric cancer risk classification from
      photofluorography.
AB  - AIM: To perform automatic gastric cancer risk classification using
      photofluorography for realizing effective mass screening as a preliminary study.
      METHODS: We used data for 2100 subjects including X-ray images, pepsinogen I and
      II levels, PGI/PGII ratio, Helicobacter pylori (H. pylori) antibody, H. pylori
      eradication history and interview sheets. We performed two-stage classification
      with our system. In the first stage, H. pylori infection status classification
      was performed, and H. pylori-infected subjects were automatically detected. In
      the second stage, we performed atrophic level classification to validate the
      effectiveness of our system. RESULTS: Sensitivity, specificity and Youden index
      (YI) of H. pylori infection status classification were 0.884, 0.895 and 0.779,
      respectively, in the first stage. In the second stage, sensitivity, specificity
      and YI of atrophic level classification for H. pylori-infected subjects were
      0.777, 0.824 and 0.601, respectively. CONCLUSION: Although further improvements
      of the system are needed, experimental results indicated the effectiveness of
      machine learning techniques for estimation of gastric cancer risk.

PMID- 29467918
TI  - Preclinical assessment of galunisertib (LY2157299 monohydrate), a first-in-class
      transforming growth factor-beta receptor type I inhibitor.
AB  - Transforming growth factor-beta (TGFbeta) is an important driver of tumor growth
      via intrinsic and extrinsic mechanisms, and is therefore an attractive target for
      developing cancer therapeutics. Using preclinical models, we characterized the
      anti-tumor activity of a small molecule inhibitor of TGFbeta receptor I
      (TGFbetaRI), galunisertib (LY2157299 monohydrate). Galunisertib demonstrated
      potent and selective inhibition of TGFbetaRI with corresponding inhibition of
      downstream signaling via inhibition of SMAD phosphorylation (pSMAD). Galunisertib
      also inhibited TGFbeta-induced pSMAD in vivo, which enabled a
      pharmacokinetic/pharmacodynamic profile in Calu6 and EMT6-LM2 tumors.
      Galunisertib demonstrated anti-tumor activity including inhibition of tumor cell
      migration and mesenchymal phenotype, reversal of TGFbeta-mediated immune
      suppression, and tumor growth delay. A concentration-effect relationship was
      established with a dosing schedule to achieve the optimal level of target
      modulation. Finally, a rat model demonstrated a correlation between galunisertib
      dependent inhibition of pSMAD in tumor tissues and in PBMCs, supporting the use
      of PBMCs for assessing pharmacodynamic effects. Galunisertib has been tested in
      several clinical studies with evidence of anti-tumor activity observed in subsets
      of patients. Here, we demonstrate that galunisertib inhibits a number of TGFbeta
      dependent functions leading to anti-tumor activity. The enhanced understanding of
      galunisertib provides rationale for further informed clinical development of
      TGFbeta pathway inhibitors.

PMID- 29467919
TI  - Interleukin-13 peptide vaccine induces protective humoral immunity in murine
      asthma models.
AB  - This study presents a rational design approach to discovery synthetic peptide
      vaccine candidates from endogenous proteins for chronic non-infectious diseases
      immunological therapeutics. The approach described the screening of key antigenic
      amino acid residues of the interleukine-13, which is up-regulated expression in
      asthma, followed by the development of immunological helper epitope peptides via
      an integrative computational and experimental method. Notably, this totally
      synthetic peptide vaccine was capable of stimulating humoral immune responses
      much stronger than those of parental antigenic peptides by enhancing the
      efficiency of antigen presentation, and had effective treatment in mouse asthma
      models. Our approach offers new possibilities to discovery therapeutic peptide
      vaccine candidates for chronic non-infectious diseases, with highly consolidated
      in silico and animal disease models for fast iterative screening.

PMID- 29467920
TI  - Idiopathic multicentric Castleman's disease: a clinicopathologic study in
      comparison with IgG4-related disease.
AB  - The present study aimed to compare clinicopathologic features between idiopathic
      multicentric Castleman's disease (n=22) and IgG4-related disease (n=26).
      Histology was analyzed using lymph node and lung biopsies. The expression of IL-6
      mRNA in tissue was also examined by in situ hybridization and real-time PCR.
      Patients with idiopathic multicentric Castleman's disease were significantly
      younger than those with IgG4-related disease (p<0.001). Splenomegaly was observed
      in only idiopathic multicentric Castleman's disease (p=0.002), while pancreatitis
      and sialo-dacryoadenitis were restricted to IgG4-related disease (both p<0.001).
      Serum IgG4 concentrations were commonly elevated at >135 mg/dL in both groups
      (p=0.270). However, the IgG4/IgG ratio in IgG4-related disease was significantly
      higher than that in Castleman's disease (p<0.001). Histologically, sheet-like
      plasmacytosis was highly characteristic of idiopathic multicentric Castleman's
      disease (p<0.001), while plasmacytic infiltration in IgG4-related disease was
      always associated with intervening lymphocytes. Similar to laboratory findings,
      the IgG4/IgG-positive plasma cell ratio, but not the IgG4-positive cell count,
      was significantly higher in IgG4-related disease (p=0.002). Amyloid-like
      hyalinized fibrosis was found in 6/8 lung biopsies (75%) of Castleman's disease.
      The over-expression of IL-6 mRNA was not confirmed in tissue samples of
      Castleman's disease by either in situ hybridization or quantitative real-time
      PCR. In conclusion, useful data for a differential diagnosis appear to be age,
      affected organs, the serum IgG4/IgG ratio, sheet-like plasmacytosis in biopsies,
      and the IgG4/IgG-positive cell ratio on immunostaining. Since IL-6 was not over
      expressed in tissue of idiopathic multicentric Castleman's disease, IL-6 may be
      produced outside the affected organs, and circulating IL-6 may lead to
      lymphoplasmacytosis at nodal and extranodal sites.

PMID- 29467921
TI  - Endoplasmic reticulum stress stimulates the release of extracellular vesicles
      carrying danger-associated molecular pattern (DAMP) molecules.
AB  - Disturbances in endoplasmic reticulum (ER) function lead to ER stress which, when
      severe or prolonged, may result in apoptosis. Severe ER stress has been
      implicated in several pathological conditions including pre-eclampsia, a
      multisystem disorder of pregnancy associated with the release of pro-inflammatory
      factors from the placenta into the maternal circulation. Here, we show that
      severe ER stress induced by two distinct mechanisms in BeWo choriocarcinoma cells
      leads to the release of extracellular vesicles (EVs) carrying pro-inflammatory
      damage-associated molecular pattern (DAMP) molecules. Co-treatment with the
      antioxidant pyrrolidine dithiocarbamate results in a reduction in ER stress
      induced EV-associated DAMP release. We further demonstrate that severe ER stress
      is associated with changes in the expression of several stress-related proteins,
      notably Cited-2 and phosphorylated JNK. Together, these data indicate that severe
      ER stress-mediated release of EV-associated DAMPs may contribute to the
      heightened systemic maternal inflammatory response characteristic of pre
      eclampsia and may also be relevant to other chronic inflammatory diseases which
      display elevated ER stress.

PMID- 29467922
TI  - Type 2 diabetes epidemic in East Asia: a 35-year systematic trend analysis.
AB  - Facing the challenge of effective prevention type 2 diabetes (T2DM) in China (as
      part of global health) requires knowledge about both the temporal trend and risk
      factors variation in T2DM. We searched the PubMed, CNKI, WANFANG, and
      International Diabetes Federation (IDF) databases for data on the prevalence of
      T2DM/ IGT (impaired glucose tolerance) published from January 1, 1980 to December
      31, 2014 in China, Japan and Korea. The prevalence of T2DM was estimated with 95%
      confidence intervals (CIs) using random-effects meta-analysis. T2DM prevalence
      trend in the next 10 years was estimated by using a time series regression model
      based on the 35 years of data. The 621 articles covered 11.8 million Chinese
      people, 1.64 million Japanese, and 37.69 million Koreans. The aggregate
      prevalence of T2DM in China has increased sharply from 1.3% in 1980-1989 to 4.5%
      in 1990-1999, 6.8% 2000-2009, and 8.7% in 2010-2014. We estimated that by 2025,
      T2DM prevalence will have grown to 12.5%. Central obesity is the largest
      preventable cause of T2DM. We also found that female having a very high BMI (body
      mass index, >=28 kg/m2) and being an older (>=50 years old) female are next
      highest risk factors for T2DM compared with male. Consistent with the patterns
      characterized for China, T2DM prevalence in Japan increased with aging, and men
      were more likely to develop T2DM. It was the same as Korea. In the Far East,
      especially in China, T2DM prevalence will continue to increase until 2025.
      Statistical analyses were conducted using Stata 12.0 and SPSS 19.0.

PMID- 29467923
TI  - Synthetic analysis of associations between IL-10 polymorphisms and skin cancer
      risk.
AB  - The current study was designed to quantitatively summarize the evidence for the
      strength of the associations between common IL-10 functional polymorphisms and
      skin cancer risk. Relevant publications concerning the associations between
      common IL-10 functional polymorphisms(-1082G>A, -819C>T and -592C>A) and skin
      cancer were retrieved by a comprehensive electronic literature search in PubMed,
      Web of Science, EBSCO, Embase, China National Knowledge Infrastructure, Wanfang,
      Chinese Biomedical Database (CBM). The odds ratio (OR) and 95% confidence
      interval (CI) were utilized to assess the strength of the relationship. A total
      of 26 studies including 4090 cases and 4133 controls (-1082G>A, 10 studies with
      1809 cases and 1830 controls; -819C>T, 7 studies with 862 cases and 957 controls;
      -592C>A, 9 studies with 1419 cases and 1346 controls) were enrolled in the meta
      analysis. Overall, the results revealed a borderline decreased risk of skin
      cancer in heterozygote model (OR = 0.82, 95CI = 0.67-1.00, p = 0.05). The
      subgroup analysis also presented similar association for non-melanoma skin cancer
      in heterozygote model (OR = 0.67, 95CI = 0.50-0.91, p = 0.01). Moreover, the
      further analysis based on the histological type of non-melanoma skin cancer
      indicated a significantly decreased risk of BCC in allele model (OR = 0.67, 95%
      CI = 0.50-0.91, p = 0.02) and dominant model (OR = 0.68, 95% CI = 0.48-0.98, p =
      0.04). However, neither overall analysis nor subgroup analysis based on cancer
      subtype revealed a significant association of -1082G>A or -592C>A polymorphisms
      with skin cancer. The present study suggested a potential association between IL
      10 -819C>T polymorphism and decreased risk of skin cancer, but a lack of
      association for -1082G>A and -592C>A polymorphisms. Further invalidation is
      urgently needed.

PMID- 29467924
TI  - Prognostic significance of Cytokeratin 20-positive lymph node vascular
      endothelial growth factor A mRNA and chromodomain helicase DNA binding protein 4
      in pN0 colorectal cancer patients.
AB  - BACKGROUND: Cytokeratin 20-positive cells in lymph nodes from pN0 colorectal
      cancer (CRC) patients were detected previously by us. The aims of this study were
      to investigate which tumor metastasis-related genes were involved and their
      potential clinical significance. RESULTS: Fourteen of 84 (17%) genes were
      differentially expressed by at least 2-fold. Among them, 10 genes were up
      regulated whereas 4 genes were down-regulated. Those differential expressed genes
      were validated in the second cohort of specimens. Follow-up analysis for 60
      months showed that patients with lymph node vascular endothelial growth factor A
      (VEGF-A) mRNA and chromodomain helicase DNA binding protein 4 (CHD4) mRNA
      expression higher than the median copies had significantly shorter time to
      recurrence than those with lower than the median copies. Multivariate analysis
      showed that VEGF-A mRNA, CHD4 mRNA and lymphatic vessel involvement were
      independent prognostic factors for disease recurrence. CONCLUSIONS: VEGF-A mRNA
      and CHD4 mRNA were up-regulated in CK20-positive pN0 lymph nodes and they may
      have prognostic significance in pN0 CRC patients. METHODS: Two cohorts of lymph
      node specimens from pN0 CRC patients of each with and without CK20-positive cells
      were recruited. In the first cohort, tumor metastasis genes were profiled using
      gene expression arrays. Differential expressed genes were validated in the second
      cohort. Moreover, their prognostic significance was examined by following-up the
      second cohort of patients with CK20-positive cells for 60 months and all
      histopathological findings were correlated to recurrence.

PMID- 29467925
TI  - Plasma YKL-40 as a biomarker for bevacizumab efficacy in patients with newly
      diagnosed glioblastoma in the phase 3 randomized AVAglio trial.
AB  - YKL-40 is a glycoprotein with pro-angiogenic functions. We hypothesized that
      patients with newly diagnosed glioblastoma and low baseline plasma YKL-40 levels
      derive greater benefit from first-line bevacizumab. Plasma samples were collected
      from 563 patients in the randomized, phase 3 AVAglio trial who received
      bevacizumab or placebo plus radiotherapy/temozolomide. Raw plasma YKL-40
      concentrations were converted to age-corrected percentiles of normal healthy YKL
      40 levels and divided into quartiles (Q). The impact of baseline plasma YKL-40
      level on survival was investigated using Cox regression analyses. Patients with
      low baseline plasma YKL-40 (<=Q1) had an improved progression-free survival
      hazard ratio (HR) for bevacizumab versus placebo (0.37, 95% confidence interval
      [CI]: 0.25-0.55) compared with high plasma YKL-40 (> Q1) (0.71, 95% CI: 0.57
      0.87). Overall survival HRs were comparable between the subgroups (<= Q1: 0.69,
      95% CI: 0.44-1.09; (> Q1: 0.88, 95% CI: 0.68-1.13). A trend for improved
      progression-free survival HR with low versus high YKL-40 was observed in
      proneural glioblastoma (0.41, 95% CI: 0.13-1.28 vs 0.80, 95% CI: 0.45-1.40,
      respectively), but not for proliferative/mesenchymal subtypes. Elevated plasma
      YKL-40 (> 90th percentile of normal) was an independent negative prognostic
      factor. In conclusion, the predictive value of baseline plasma YKL-40 level as a
      biomarker for bevacizumab efficacy in glioblastoma may be limited to patients
      with proneural tumors. Independent validation studies are required to confirm
      these results.

PMID- 29467926
TI  - Distinct pattern of cerebral blood flow alterations specific to schizophrenics
      experiencing auditory verbal hallucinations with and without insight: a pilot
      study.
AB  - Schizophrenia is associated with widespread and complex cerebral blood flow (CBF)
      disturbance. Auditory verbal hallucinations (AVH) and insight are the core
      symptoms of schizophrenia. However, to the best of our knowledge, very few
      studies have assessed the CBF characteristics of the AVH suffered by
      schizophrenic patients with and without insight. Based on our previous findings,
      Using a 3D pseudo-continuous ASL (pcASL) technique, we investigated the
      differences in AVH-related CBF alterations in schizophrenia patients with and
      without insight. We used statistical parametric mapping (SPM8) and statistical
      non-parametric mapping (SnPM13) to perform the fMRI analysis. We found that AVH
      schizophrenia patients without insight showed an increased CBF in the left
      temporal pole and a decreased CBF in the right middle frontal gyrus when compared
      to AVH-schizophrenia patients with insight. Our novel findings suggest that AVH
      schizophrenia patients without insight possess a more complex CBF disturbance.
      Simultaneously, our findings also incline to support the idea that the CBF
      aberrant in some specific brain regions may be the common neural basis of insight
      and AVH. Our findings support the mostly current hypotheses regarding AVH to some
      extent. Although our findings come from a small sample, it provide the evidence
      that indicate us to conduct a larger study to thoroughly explore the mechanisms
      of schizophrenia, especially the core symptoms of AVHs and insight.

PMID- 29467927
TI  - Kanglaite inhibits EMT caused by TNF-alpha via NF-kappaBeta inhibition in
      colorectal cancer cells.
AB  - Tumor necrosis factor-alpha is a critical pro-inflammatory cytokine produced by
      macrophages and was once considered an anti-tumor agent. However, a low dose of
      tumor necrosis factor-alpha can cause epithelial mesenchymal transition,
      angiogenesis and metastasis. NF-kappaBeta contributes to epithelial mesenchymal
      transition induced by tumor necrosis factor-alpha. Kanglaite, an extract from the
      Coix lacryma-jobi (adlay) seed, is an NF-kappaBeta inhibitor. The aim of this
      study was to investigate whether Kanglaite could inhibit epithelial mesenchymal
      transition caused by tumor necrosis factor-alpha using four colorectal cancer
      cell lines, HCT106, HCT116, LoVo and CT26. Our results showed that tumor necrosis
      factor-alpha -mediated activation of NF-kappaBeta, caused changes in epithelial
      mesenchymal transition -related protein expression, and increased migration and
      invasion in all four cell lines. However, these effects were inhibited by
      Kanglaite when used in combination with tumor necrosis factor-alpha. In a
      subcutaneous tumor model of CT26, tumor necrosis factor-alpha enhanced the
      tumorigenic ability of the cells, and again this was inhibited by Kanglaite.
      However, treatment with Kanglaite alone caused almost no inhibition of epithelial
      mesenchymal transition -mediated tumor growth, when cells were pretreated with
      tumor necrosis factor-alpha prior to injection. These results suggest that
      Kanglaite inhibits tumor necrosis factor-alpha -mediated epithelial mesenchymal
      transition in colorectal cancer cell lines via inhibition of NF-kappaBeta.

PMID- 29467928
TI  - Inferring modes of evolution from colorectal cancer with residual polyp of
      origin.
AB  - Besides the classical evolutionary model of colorectal cancer (CRC) defined by
      the stepwise accumulation of mutations in which normal epithelium transforms
      through an intermediary polyp stage to cancer, a few studies have proposed
      alternative modes of evolution (MOE): early eruptive subclonal expansion,
      branching of the subclones in parallel evolution, and neutral evolution. However,
      frequencies of MOEs and their connection to mutational characteristics of cancer
      remain elusive. In this study, we analyzed patterns of somatic single nucleotide
      variations (SNVs) and copy number aberrations (CNAs) in CRC with residual polyp
      of origin from 13 patients in order to determine this relationship. For each MOE
      we defined an expected pattern with characteristic features of allele frequency
      distributions for SNVs in cancers and their matching adenomas. From these
      distinct patterns, we then assigned an MOE to each CRC case and found that
      stepwise progression was the most common (70% of cases). We found that CRC with
      the same MOE may exhibit different mutational spectra, suggesting that different
      mutational mechanisms can result in the same MOE. Inversely, cancers with
      different MOEs can have the same mutational spectrum, suggesting that the same
      mutational mechanism can lead to different MOEs. The types of somatic
      substitutions, distribution of CNAs across genome, and mutated pathways did not
      correlate with MOEs. As this could be due to small sample size, these relations
      warrant further investigation. Our study paves the way to connect MOE with
      clinical and mutational characteristics not only in CRC but also to neoplastic
      transformation in other cancers.

PMID- 29467929
TI  - The SNPs in pre-miRNA are related to the response of capecitabine-based therapy
      in advanced colon cancer patients.
AB  - The single nucleotide polymorphisms (SNPs) in the microRNA precursor (pre-miRNA)
      may modulate the posttranscriptional regulation of gene expression and explain
      individual sensitivity to chemotherapy. Here we investigated the correlation
      between 23 SNPs in the pre-miRNA and the efficacy of capecitabine-based
      chemotherapy in 274 advanced colon cancer patients. Statistical analysis
      indicated that much more patients with rs744591 A/C(48.03%), C/C (53.45%) or C
      allele (49.73%) responded to the chemotherapy than those with the A/A genotype
      (33.71%). The response rates of rs745666 G/C heterozygous patients (35.25%) and C
      allele carriers (39.69%) were apparently less than that of the G/G homozygous
      patients (56.25%). Moreover, three SNPs rs2114358, rs35770269, and rs73239138
      were significantly associated with the occurrence of side effects of
      chemotherapy. The patients with rs2114358 C allele (OR = 2.016) or rs35770269 T
      allele (OR = 2.299) were much more prone to endure adverse events. However, the
      incidence of side effect was lower in the patients carrying rs73239138 A allele
      than those with G/G genotype (OR = 0.500). Our findings demonstrate that genetic
      variations in pre-miRNA may influence the efficacy of capecitabine-based
      chemotherapy in advanced colon cancer patients.

PMID- 29467930
TI  - Identification of the potential crucial genes in invasive ductal carcinoma using
      bioinformatics analysis.
AB  - Invasive ductal carcinoma (IDC) is a common histological type of breast cancer.
      The aim of this study was to identify the potential crucial genes associated with
      IDC and to provide valid biological information for further investigations. The
      gene expression profiles of GSE10780 which contained 42 histologically normal
      breast tissues and 143 IDC tissues were downloaded from the GEO database.
      Functional and pathway enrichment analysis of differentially expressed genes
      (DEGs) were performed and protein-protein interaction (PPI) network was analyzed
      using Cytoscape. In total, 999 DEGs were identified, including 667 up-regulated
      and 332 down-regulated DEGs. Gene ontology analysis demonstrated that most DEGs
      were significantly enriched in mitotic cell cycle, adhesion and protein binding
      process. Through PPI network analysis, a significant module was screened out, and
      the top 10 hub genes, CDK1, CCNB1, CENPE, CENPA, PLK1, CDC20, MAD2L1, HIST1H2BK,
      KIF2C and CCNA2 were identified from the PPI network. The expression levels of
      the 10 genes were validated in Oncomine database. KIF2C, MAD2L1 and PLK1 were
      associated with the overall survival. And we used cBioPortal to explore the
      genetic alterations of hub genes and potential drugs. In conclusion, the present
      study identified DEGs between normal and IDC samples, which could improve our
      understanding of the molecular mechanisms in the development of IDC, and these
      candidate genes might be used as therapeutic targets for IDC.

PMID- 29467931
TI  - Toll-like receptor 2 induces adenosine receptor A2a and promotes human squamous
      carcinoma cell growth via extracellular signal regulated kinases 1/2.
AB  - Patient treatment for oral squamous cell carcinoma (OSCC) not associated with
      Human papillomavirus remains problematic. OSCC microenvironment is typically
      inflamed and colonized by microorganisms, providing ligands for toll-like
      receptors (TLR). In immune cells TLR2 and TLR4 activate NF-kB and extracellular
      signal regulated kinase (ERK)1/2 pathways, leading to upregulation of inhibitory
      adenosine receptors A2a and A2b, and reduction in stimulatory A1 and A3. How TLR
      and adenosine receptors function in SCC cells is not understood. To address this
      gap, we evaluated TLR and adenosine receptor expression and function in human
      OSCC cells and keratinocytes. TLR2 and A2a were co-expressed in pre-cancer and
      SCC cells of 17 oral specimens. In vitro, 5/6 OSCC lines expressed more TLR2 than
      TLR1, 4 or 6 mRNA. TLR2 ligands stimulated A2a expression in TLR2-high cell
      lines, but no A1 or A3 was detected with or without stimuli. In TLR2-high OSCC,
      TLR2/1, 2/6 and adenosine receptor agonists activated ERK1/2. TLR2-mediated
      ERK1/2 phosphorylation resulted in accumulation of c-FOS, ERK-dependent cell
      proliferation and reduced caspase-3 activity. Similar ERK1/2-dependent
      proliferation and decreased caspase-3 activity were caused by combined TLR2 and
      adenosine receptor stimuli. We conclude that TLR2 and adenosine receptor
      agonists, known to be present in the tumor microenvironment, may contribute to
      OSCC progression in part via direct effects on the ERK1/2 pathway in squamous
      carcinoma cells.

PMID- 29467932
TI  - Characterization of aptamer-mediated gene delivery system for liver cancer
      therapy.
AB  - Liver cancer is a fatal disease with limited therapy options. The recombinant
      adenovirus expressing tumor-suppressor gene of PTEN (Ad5-PTEN) showed effective
      antitumor activity against liver cancer. However, its disadvantages produced
      great limitation on its application, especially its nonspecific and toxicity to
      normal cells and tissues. The epithelial cell adhesion molecule (EpCAM) is over
      expressed in some liver cancer cells and an RNA aptamer EpDT3 could specially
      target to EpCAM-positive cells. Based on this founding, we aimed to design a kind
      of gene delivery system of EpDT3-mediated Ad5-PTEN (EpDT3-PEG-Ad5-PTEN, EPAP) in
      which polyethylene glycol was used to be a linker to conjugate EpDT3 with Ad5
      PTEN. This strategy may overcome the disadvantages of naked Ad5-PTEN and enhance
      the antitumor effect on liver cancer. The SDS-PAGE electrophoresis, TBE-PAGE
      electrophoresis and fluorescence detection were conducted to confirm the
      successful preparation of EPAP. Compared with the naked Ad5-PTEN, EPAP showed
      significant anti-proliferative and anti-migratory activities against HepG2 cells.
      EPAP also showed selective and precise target ability to EpCAM-positive HepG2
      cells in vivo. Therefore, EPAP may be further explored as a novel effective
      anticancer drug for malignant liver cancer.

PMID- 29467933
TI  - Determinants of variability of five programmed death ligand-1
      immunohistochemistry assays in non-small cell lung cancer samples.
AB  - Programmed death ligand-1 (PD-L1) expression as determined by
      immunohistochemistry (IHC) is potentially predictive of clinical outcome. The aim
      of this study was to assess the concordance of reported PD-L1 IHC assays and
      investigate factors influencing variability. Consecutive sections from 20 non
      small cell lung cancers (NSCLCs) comprising resection, core biopsy, cytology and
      pleural fluid samples underwent IHC with 5 different antibody/autostainer
      combinations: 22C3/Link48, 28-8/BOND-MAX, E1L3N/BOND-MAX, SP142/BenchMark and
      SP263/BenchMark. PD-L1 RNA levels were assessed using RNAscope. The frequency of
      positive cases using scoring thresholds from clinical trials was 72%, 33%, 61%,
      56%, and 33% for the 5 IHC protocols respectively, and 33% for RNAscope. Pairwise
      agreement on the classification of cases as positive or negative for PD-L1
      expression ranged from 61%-94%. On a continuous scale, the lowest correlation was
      between 28-8/BOND-MAX and SP142/BenchMark (R2=0.25) and highest was between
      22C3/Link48 and E1L3N/BOND-MAX (R2=0.71). When cases were ordered according to
      tumor cell (TC)%, a similar ranking of cases across IHC protocols could be
      observed, albeit with different quanta and limits of detection. Single-slide OPAL
      7-color fluorescence IHC analysis revealed a high degree of co-localization of
      staining from the 5 PD-L1 antibodies. Using SP142 antibody in a BOND-MAX protocol
      led to increased TC% quanta, while retaining a similar ranking of samples
      according to TC%. The results of this study highlight tumor PD-L1 status can vary
      significantly according to IHC protocol. Protocol-dependent staining intensities
      and nominated thresholds for positivity contribute to this variability, while the
      antibody used appears to be less of a factor.

PMID- 29467934
TI  - Effects of STC1 overexpression on tumorigenicity and metabolism of hepatocellular
      carcinoma.
AB  - Stanniocalcin-1 (STC1) is a paracrine factor associated with inflammation and
      carcinogenesis. Using clinicopathological data, we previously reported that a
      greater expression of STC1 in hepatocellular carcinoma (HCC) was significantly
      correlated with smaller tumor size. The underlying mechanism on the correlation
      is not known. In this study, using a metastatic HCC cell-line (MHCC-97L, P) and
      lentiviral vector mediated-STC1 overexpression, the inoculation of STC1
      overexpressing MHCC-97L (S1) cells in a nude mice xenograft model demonstrated
      reductions in tumor mass and volume. As compared with P cells, S1 cells exhibited
      epithelial phenotype with significantly lower plating efficiency and reduced
      migratory and proliferative potential. Using coulter counter for cell-sizing, S1
      cells (17.6 MUm) were significantly smaller than P cells (19.6 MUm). Western blot
      analysis revealed that S1 cells exhibited reduced expression level of
      phosphorylated ribosomal protein S6 (p-rpS6). Moreover, an inhibition of the
      upstream kinase p70S6K was evident with the dephosphorylation of Thr389 in the
      linker domain of the kinase. The inhibition of p70S6K/p-rpS6 pathway was
      accompanied with reduced cellular ATP level and increase of p-AMPK in S1 cells.
      Significantly lower rates of glycolysis and extracellular O2 consumption in S1
      cells exhibited a lower cellular energy status. Since a faster rate of ATP
      production is essential to support cancer growth and metastasis, the present
      study identified the effect of STC1-overexpression on reducing energy metabolism,
      leading to an activation of AMPK pathway but an inhibition of p70S6K/p-rpS6
      signaling to reduce tumor growth.

PMID- 29467935
TI  - A robust gene expression-based prognostic risk score predicts overall survival of
      lung adenocarcinoma patients.
AB  - Identification of reliable predictive biomarkers and new therapeutic targets is a
      critical step for significant improvement in patient outcomes. Here, we developed
      a multi-step bioinformatics analytic strategy to mine large omics and clinical
      data to build a prognostic scoring system for predicting the overall survival
      (OS) of lung adenocarcinoma (LuADC) patients. In latter we first identified 1327
      significantly and robustly deregulated genes, 600 of which were significantly
      associated with the OS of LuADC patients. Gene co-expression network analysis
      revealed the biological functions of these 600 genes in normal lung and LuADCs,
      which were found to be enriched for cell cycle-related processes, blood vessel
      development, cell-matrix adhesion and metabolic processes. Finally, we
      implemented a multiple resampling method combined with Cox regression analysis to
      identify a 27-gene signature associated with OS, and then created a prognostic
      scoring system based on this signature. This scoring system robustly predicted OS
      of LuADC patients in 100 sampling test sets and was further validated in four
      independent LuADC cohorts. In addition, in comparison to other existing
      prognostic gene signatures published in the literature, our signature was
      significantly superior in predicting OS of LuADC patients. In summary, our multi
      omics and clinical data integration study created a 27-gene prognostic risk score
      that can predict OS of LuADC patients independent of age, gender and clinical
      stage. This score could guide therapeutic selection and allow stratification in
      clinical trials.

PMID- 29467936
TI  - Dynamic changes in CD44v-positive cells after preoperative anti-HER2 therapy and
      its correlation with pathologic complete response in HER2-positive breast cancer.
AB  - Chemotherapy has been reported to increase the proportion of cancer stem cells
      (CSCs) and to promote epithelial-mesenchymal transition (EMT) phenotype changes.
      Anti-HER2 therapy may provide a strategy for eliminating CSC and EMT, which
      contribute to therapeutic resistance. No study has determined the changes in the
      quantity or characteristics of CSCs or circulating tumor cells (CTCs) with EMT
      phenotype during preoperative anti-HER2 therapy, and whether these changes
      correlate to response to dual anti-HER2 therapy. In a prospective clinical trial
      to evaluate pharmacodynamic biomarkers, 18 patients with operable primary HER2
      positive breast cancer received dual anti-Her2 preoperative therapy with
      trastuzumab and lapatinib with paclitaxel. Proportions of tumor cells with CSC
      characteristics and EMT markers in CTC's were estimated at baseline, after 6 and
      18 weeks of preoperative therapy to determine the quantitative cutoff value to
      predict pathologic complete response (pCR). Out of 18 patients, 8 (44%) had a
      pCR; 5 of these 8 patients (62%) were positive for CD44v at baseline and none
      were positive on the 6-week biopsy. In contrast, 6 of the 10 patients without pCR
      exhibited persistent levels, or enrichment of CD44v proportion and expression at
      6 and 18 weeks (p=0.0128). Other biomarkers were not statistically significant
      predictors of pCR. Enrichment of CD44v-positive tumor cells after dual anti-HER2
      therapy alone may predict poor response to dual anti-HER2 therapy plus
      chemotherapy.

PMID- 29467937
TI  - Temozolomide, sirolimus and chloroquine is a new therapeutic combination that
      synergizes to disrupt lysosomal function and cholesterol homeostasis in GBM
      cells.
AB  - Glioblastoma (GBM) cells are characterized by high phagocytosis, lipogenesis,
      exocytosis activities, low autophagy capacity and high lysosomal demand are
      necessary for survival and invasion. The lysosome stands at the cross roads of
      lipid biosynthesis, transporting, sorting between exogenous and endogenous
      cholesterol. We hypothesized that three already approved drugs, the autophagy
      inducer, sirolimus (rapamycin, Rapa), the autophagy inhibitor, chloroquine (CQ),
      and DNA alkylating chemotherapy, temozolomide (TMZ) could synergize against GBM.
      This repurposed triple therapy combination induced GBM apoptosis in vitro and
      inhibited GBM xenograft growth in vivo. Cytotoxicity is caused by induction of
      lysosomal membrane permeabilization and release of hydrolases, and may be rescued
      by cholesterol supplementation. Triple treatment inhibits lysosomal function,
      prevents cholesterol extraction from low density lipoprotein (LDL), and causes
      clumping of lysosome associated membrane protein-1 (LAMP-1) and lipid droplets
      (LD) accumulation. Co-treatment of the cell lines with inhibitor of caspases and
      cathepsin B only partially reverse of cytotoxicities, while N-acetyl cysteine
      (NAC) can be more effective. A combination of reactive oxygen species (ROS)
      generation from cholesterol depletion are the early event of underling mechanism.
      Cholesterol repletion abolished the ROS production and reversed the cytotoxicity
      from QRT treatment. The shortage of free cholesterol destabilizes lysosomal
      membranes converting aborted autophagy to apoptosis through either direct
      mitochondria damage or cathepsin B release. This promising anti-GBM triple
      therapy combination severely decreases mitochondrial function, induces lysosome
      dependent apoptotic cell death, and is now poised for further clinical testing
      and validation.

PMID- 29467938
TI  - SMAD4-independent activation of TGF-beta signaling by MUC1 in a human pancreatic
      cancer cell line.
AB  - Pancreatic Ductal Adenocarcinoma (PDA) has a mortality rate that nearly matches
      its incidence rate. Transforming Growth Factor Beta (TGF-beta) is a cytokine with
      a dual role in tumor development switching from a tumor suppressor to a tumor
      promoter. There is limited knowledge of how TGF-beta function switches during
      tumorigenesis. Mucin 1 (MUC1) is an aberrantly glycosylated, membrane-bound,
      glycoprotein that is overexpressed in >80% of PDA cases and is associated with
      poor prognosis. In PDA, MUC1 promotes tumor progression and metastasis via
      signaling through its cytoplasmic tail (MUC1-CT) and interacting with other
      oncogenic signaling molecules. We hypothesize that high levels of MUC1 in PDA may
      be partly responsible for the TGF-beta functional switch during oncogenesis. We
      report that overexpression of MUC1 in BxPC3 human PDA cells (BxPC3.MUC1) enhances
      the induction of epithelial to mesenchymal transition leading to increased
      invasiveness in response to exogenous TGF-beta1. Simultaneously, these cells
      resist TGF-beta induced apoptosis by downregulating levels of cleaved caspases.
      We show that mutating the tyrosines in MUC1-CT to phenylalanine reverses the TGF
      beta induced invasiveness. This suggests that the tyrosine residues in MUC1-CT
      are required for TGF-beta induced invasion. Some of these tyrosines are
      phosphorylated by the tyrosine kinase c-Src. Thus, treatment of BxPC3.MUC1 cells
      with a c-Src inhibitor (PP2) significantly reduces TGF-beta induced invasiveness.
      Similar observations were confirmed in the Chinese hamster ovarian (CHO) cell
      line. Data strongly suggests that MUC1 may regulate TGF-beta function in PDA
      cells and thus have potential clinical relevance in the use of TGF-beta
      inhibitors in clinical trials.

PMID- 29467939
TI  - Socioeconomic status is inversely associated with esophageal squamous cell
      carcinoma risk: results from a population-based case-control study in China.
AB  - Socioeconomic status (SES) is suspected to influence the risk of esophageal
      squamous-cell carcinoma (ESCC) in China, however, the evidence is still
      inconclusive and the selection of SES indicators remains inconsistent. In current
      study, we examined the association between SES and risk of ESCC based on a
      population-based case-control study in Taixing, China, with 1298 histopathology
      confirmed cases and 1900 controls recruited between October 2010 and September
      2013. Data on SES indicators was collected using a structured questionnaire. We
      constructed a composite wealth score based on the ownership of a series of
      household appliances and other variables by using multiple correspondence
      analysis (MCA). We used unconditional logistic regression to estimate odds ratios
      (ORs) with 95% confidence intervals (CIs) of ESCC in association with SES
      indicators. SES was inversely associated with ESCC risk in current study. Higher
      education (secondary high school or above vs illiteracy, OR=0.60, 95%CI, 0.41
      0.87), larger house area per person (>70 vs <45 square meters, OR=0.71, 95%CI,
      0.59-0.86) and higher wealth score (5th quintile (high) vs 1st quintile (low),
      OR=0.43, 95%CI, 0.32-0.57) were associated with a decreased risk of ESCC.
      Subjects possessing several household appliances >5 years also had a lower ESCC
      risk. Whereas physical labor (very active vs sedentary, OR=1.69, 95%CI, 1.27
      2.26) and larger families (>=6 vs <3 in household, OR=1.63, 95%CI, 1.30-2.03)
      increased the risk of ESCC. These findings confirm the strong inverse association
      between SES and ESCC risk. Future studies are needed to verify these findings and
      identify contributing factors underlying the observed associations.

PMID- 29467940
TI  - ZB716, a steroidal selective estrogen receptor degrader (SERD), is orally
      efficacious in blocking tumor growth in mouse xenograft models.
AB  - Advances in oral SERDs development so far have been confined to nonsteroidal
      molecules such as those containing a cinnamic acid moiety, which are in
      earlystage clinical evaluation. ZB716 was previously reported as an orally
      bioavailable SERD structurally analogous to fulvestrant. In this study, we
      examined the binding details of ZB716 to the estrogen receptor alpha (ERalpha) by
      computer modeling to reveal its interactions with the ligand binding domain as a
      steroidal molecule. We also found that ZB716 modulates ERalpha-coregulator
      interactions in nearly identical manner to fulvestrant. The ability of ZB716 to
      inhibit cell growth and downregulate ER expression in endocrine resistant,
      ERalpha mutant breast cancer cells was demonstrated. Moreover, in both the MCF-7
      xenograft and a patient derived xenograft model, orally administered ZB716 showed
      superior efficacy in blocking tumor growth when compared to fulvestrant.
      Importantly, such enhanced efficacy of ZB716 was shown to be attributable to its
      markedly higher bioavailability, as evidenced in the final plasma and tumor
      tissue concentrations of ZB716 in mice where drug concentrations were found
      significantly higher than in the fulvestrant treatment group.

PMID- 29467941
TI  - Spiclomazine displays a preferential anti-tumor activity in mutant KRas-driven
      pancreatic cancer.
AB  - Ras-targeted therapy represents a 'holy grail' in oncology. Based on our model
      prediction, Spiclomazine freezing the intermediate conformation of activated Ras
      is central to cancer therapeutics. We show here that Spiclomazine leads to an
      effective suppression in Ras-mediated signaling through abrogating the KRas-GTP
      level in the KRas-driven pancreatic cancer. The Ras-mediated signaling inhibition
      leads to dramatically reduced survivals of five KRas-driven pancreatic cancer
      cell lines with IC50 ranging 19.7~74.2 MUM after 48 hours of treatment. However,
      no significant changes have been observed for normal cell lines. It is worth
      mentioning that the mutant KRas-driven cancer cells are more sensitive towards
      Spiclomazine than the wild-type KRas cancer cells. Subsequent cellular thermal
      shift and RNA interference assays show that Spiclomazine efficiently binds with
      and stabilizes KRas to a certain extent within the cells. This validates the
      effect of target engagement on drug efficacy. Furthermore, Spiclomazine arrests
      cell cycle at G2 phase in the cancer cells, without obvious cell-cycle arrest in
      the normal cells. This further demonstrates its selectively biological response
      to cancer cells involved in Ras-GTP-mediated target engagement. Spiclomazine
      completely inhibits the growth of MIA PaCa-2 tumors on renal capsule xenograft
      models in BALB/c mice administered 68 mg kg-1 for 2 weeks via intra-peritoneal
      route. Immunohistochemical analyses reveal the reduced c-Raf and p-ERK and the
      increase in TUNEL staining. These observations further confirm the in vitro
      findings. Taken together, Spiclomazine is a selective inhibitor for mutant KRas
      driven pancreatic cancer.

PMID- 29467942
TI  - In vitro, in vivo and ex vivo demonstration of the antitumoral role of hypocretin
      1/orexin-A and almorexant in pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is still the poorest prognostic tumor of
      the digestive system. We investigated the antitumoral role of orexin-A and
      almorexant in PDAC. We analyzed the orexin receptor type 1 (OX1R) expression by
      immunohistochemistry in human normal pancreas, PDAC and its precursor dysplastic
      intraepithelial lesions. We used PDAC-derived cell lines and fresh tissue slices
      to study the apoptotic role of hypocretin-1/orexin-A and almorexant in vitro and
      ex vivo. We analyzed in vivo the hypocretin-1/orexin-A and almorexant effect on
      tumor growth in mice xenografted with PDAC cell lines expressing, or not, OX1R.
      Ninety-six percent of PDAC expressed OX1R, while adjacent normal exocrine
      pancreas did not. OX1R was expressed in pre-cancerous lesions. In vitro, under
      hypocretin-1/orexin-A and almorexant, the OX1R-positive AsPC-1 cells underwent
      apoptosis, abolished by the tyrosine phosphatase SHP2 inhibitor, NSC-87877,
      whereas the OX1R-negative HPAF-II cell line did not. These effects were mediated
      by phosphorylation of OX1R and recruitment of SHP2. Ex vivo, caspase-3 positive
      tumor cells were significantly higher in fresh tumour slices treated 48h with
      hypocretin-1/orexin-A, as compared to control, whereas cellular proliferation,
      assessed by Ki-67 index, was not modified. In vivo, when AsPC-1 cells or patient
      derived cells were xenografted in nude mice, hypocretin-1/orexin-A or almorexant,
      administrated both starting the day of cell line inoculation or after tumoral
      development, strongly slowed tumor growth. Hypocretin-1/orexin-A and almorexant
      induce, through OX1R, the inhibition of PDAC cellular growth by apoptosis.
      Hypocretins/orexins and almorexant might be powerful candidates for the treatment
      of PDAC.

PMID- 29467943
TI  - The modified glasgow prognostic score is an independent prognostic indicator in
      neoadjuvantly treated adenocarcinoma of the esophagogastric junction.
AB  - The modified Glasgow Prognostic Score (mGPS) combines the indicators of decreased
      plasma albumin and elevated CRP. In a number of malignancies, elevated mGPS is
      associated with poor survival. Aim of this study was to investigate the
      prognostic role of mGPS in patients with neoadjuvantly treated adenocarcinomas of
      the esophagogastric junction 256 patients from a prospective database undergoing
      surgical resection after neoadjuvant treatment between 2003 and 2014 were
      evaluated. mGPS was scored as 0, 1, or 2 based on CRP (>1.0 mg/dl) and albumin
      (<35 g/L) from blood samples taken prior (preNT-mGPS) and after (postNT-mGPS)
      neoadjuvant therapy. Scores were correlated with clinicopathological patients'
      characteristics. From 155 Patients, sufficient data was available. Median follow
      up was 63.8 months (33.3-89.5 months). In univariate analysis, Cox proportional
      hazard model shows significant shorter patients OS (p = 0.04) and DFS (p = 0.02)
      for increased postNT-mGPS, preNT-hypoalbuminemia (OS: p = 0.003; DFS: p = 0.002)
      and post-NT-CRP (OS: p = 0.03; DFS: p = 0.04). Elevated postNT-mGPS and preNT
      hypoalbuminemia remained significant prognostic factors in multivariate analysis
      for OS (p = 0.02; p = 0.005,) and DFS (p = 0.02, p = 0.004) with tumor
      differentiation and tumor staging as significant covariates. PostNT-mGPS and
      preNT-hypoalbuminemia are independent prognostic indicators in patients with
      neoadjuvantly treated adenocarcinomas of the esophagogastric junction and
      significantly associated with diminished OS and DFS.

PMID- 29467944
TI  - Distinct expression of CDCA3, CDCA5, and CDCA8 leads to shorter relapse free
      survival in breast cancer patient.
AB  - Breast cancer is a dangerous disease that results in high mortality rates for
      cancer patients. Many methods have been developed for the treatment and
      prevention of this disease. Determining the expression patterns of certain target
      genes in specific subtypes of breast cancer is important for developing new
      therapies for breast cancer. In the present study, we performed a holistic
      approach to screening the mRNA expression of six members of the cell division
      cycle-associated gene family (CDCA) with a focus on breast cancer using the
      Oncomine and The Cancer Cell Line Encyclopedia (CCLE) databases. Furthermore,
      Gene Expression-Based Outcome for Breast Cancer Online (GOBO) was also used to
      deeply mine the expression of each CDCA gene in clinical breast cancer tissue and
      breast cancer cell lines. Finally, the mRNA expression of the CDCA genes as
      related to breast cancer patient survival were analyzed using a Kaplan-Meier
      plot. CDCA3, CDCA5, and CDCA8 mRNA expression levels were significantly higher
      than the control sample in both clinical tumor sample and cancer cell lines.
      These highly expressed genes in the tumors of breast cancer patients dramatically
      reduced patient survival. The interaction network of CDCA3, CDCA5, and CDCA8 with
      their co-expressed genes also revealed that CDCA3 expression was highly
      correlated with cell cycle related genes such as CCNB2, CDC20, CDKN3, and CCNB1.
      CDCA5 expression was correlated with BUB1 and TRIP13, while CDCA8 expression was
      correlated with BUB1 and CCNB1. Altogether, these findings suggested CDCA3,
      CDCA5, and CDCA8 could have a high potency as targeted breast cancer therapies.

PMID- 29467946
TI  - The prognostic efficacy of cell-free DNA hypermethylation in colorectal cancer.
AB  - Epigenetic alterations in colorectal cancer (CRC) cause important differences in
      the underlying tumor biology and aggressiveness. DNA hypermethylation is central
      for the development of CRC but the prognostic impact remains elusive. We aimed to
      assess the association between cell-free hypermethylated DNA and stage and
      survival in colorectal cancer (CRC). We analyzed pre-treatment plasma samples
      from 193 patients with CRC. Thirty gene-promoter regions were analyzed using
      methylation specific PCR. We compared the median number (range) of
      hypermethylated promoter regions with CRC stage, and constructed a multivariable
      Cox-regression model adjusted for stage, to evaluate the added prognostic
      information. The median number of hypermethylated promoter regions was nine (0
      28) in patients with distant metastasis compared to five (0-19) in patients
      without metastatic disease (p < 0.0001). The majority of the hypermethylated
      promoter regions inferred a poor prognosis. Cox-regression analysis adjusted for
      patient age, sex, pre-treatment CEA-levels, and disease stage, showed that RARB
      (HR = 1.99, 95% CI [1.07, 3.72]) and RASSF1A (HR = 3.35, 95% CI [1.76, 6.38])
      hypermethylation inferred a significant effect on survival. The risk of
      metastasis increase with the number of cell-free hypermethylated promoter
      regions. The presence of RARB and RASSF1A hypermethylation indicated aggressive
      disease, regardless of stage at the time of diagnosis.

PMID- 29467945
TI  - A comparative study of PD-L1 immunohistochemical assays with four reliable
      antibodies in thymic carcinoma.
AB  - Currently, four immunohistochemical assays are registered with the US Food and
      Drug Administration to detect the expression of PD-L1. We investigated the PD-L1
      expression in thymic carcinomas using these four diagnostic assays. The cases of
      53 patients were reviewed and their specimens were subjected to four PD-L1 assays
      with different antibodies (SP142, SP263, 22C3, and 28-8). The PD-L1 expression in
      tumor cells (TCs) and immune cells (ICs) was evaluated. In TCs, the four assays
      showed similar scores in each case. Histopathologically, high TC scores were
      observed in squamous cell carcinomas (SqCCs). Meanwhile, there were no
      significant relationships among the IC scores in the four assays. In SqCCs, the
      high expression of PD-L1 (defined as >=50% TC score) in TCs tended to be
      associated with early stage cancer. The patients with high expression levels of
      PD-L1 tended to show longer overall survival in the 22C3 assays (p=0.0200). In
      thymic carcinomas, the staining pattern showed high concordance among the four
      assays when TCs - rather than ICs - were stained. High PD-L1 positivity in TCs,
      especially in SqCCs, indicated that PD-1/PD-L1 targeted therapy may be a
      promising therapeutic approach.

PMID- 29467947
TI  - Metformin inhibits TGF-beta1-induced epithelial-to-mesenchymal transition-like
      process and stem-like properties in GBM via AKT/mTOR/ZEB1 pathway.
AB  - Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults. In
      spite of advances in diagnosis and therapy, the prognosis is still relatively
      poor. The invasive property of GBM is the major cause of death in patients.
      Epithelial-to-mesenchymal transition-like process (EMT-like process) is
      considered to play an important role in the invasive property. Metformin has been
      reported as a regulator of EMT-like process. In this study, we confirmed that
      metformin inhibited TGF-beta1-induced EMT-like process and EMT-associated
      migration and invasion in LN18 and U87 GBM cells. Our results also showed that
      metformin significantly suppressed self-renewal capacity of glioblastoma stem
      cells (GSCs), and expression of stem cell markers Bmi1, Sox2 and Musashi1,
      indicating that metformin can inhibit cancer stem-like properties of GBM cells.
      We further clarified that metformin specifically inhibited TGF-beta1 activated
      AKT, the downstream molecular mTOR and the leading transcription factor ZEB1.
      Taken together, our data demonstrate that metformin inhibits TGF-beta1-induced
      EMT-like process and cancer stem-like properties in GBM cells via AKT/mTOR/ZEB1
      pathway and provide evidence of metformin for further clinical investigation
      targeted GBM.

PMID- 29467948
TI  - Challenges in using liquid biopsies for gene expression profiling.
AB  - Circulating tumor cells (CTCs) have potential utility as a surrogate biomarker of
      tumor biology via a liquid biopsy. The aim of this study was to evaluate if the
      nCounter NanoString assay could be used for accurate gene expression profiling of
      CTCs using the PAM50 research-use-only CodeSet. Analysis was performed on CTCs
      isolated by the ANGLE Parsortix system from healthy blood spiked with the breast
      cancer cell lines Hs578T, SkBr3, MDA-MB-231 or MCF7. Using cell lines as gold
      standard positive controls and Parsortix processed blood without spiking
      (unspiked) as negative controls, we found an average of 12 significantly
      differentially expressed genes among spiked samples versus unspiked controls. We
      validated our findings with the NanoStringDiff differential expression
      statistical method. The NanoString recommended targeted pre-amplification
      introduced false positive results due to pre-amplification bias, and the
      amplification of non-cancer genes from normal leukocytes confounded gene
      expression profiling of CTCs. Pre-amplification bias is a concern for other
      similar assays that may be used as discovery tools or target validation of
      transcripts of interest in gene expression profiling of CTCs. We recommend the
      use of an unspiked negative control when evaluating CTC technologies regarding
      gene expression profiling. Given that the molecular profiling of CTCs as a liquid
      biopsy may have clinical ramifications for potential treatment selection in
      future clinical trials, our study emphasizes cautious consideration of pre
      analytical variables such as amplification bias in the context of liquid biopsy
      studies.

PMID- 29467949
TI  - Identification and characterisation of NANOG+/ OCT-4high/SOX2+ doxorubicin
      resistant stem-like cells from transformed trophoblastic cell lines.
AB  - Treatment of gestational trophoblastic diseases (GTD) involves surgery,
      radiotherapy and chemotherapy. Although, these therapeutic approaches are highly
      successful, drug resistance and toxicity remain a concern for high risk patients.
      This Chemoresistance has also been observed in the presence of cancer stem cells
      that are thought to be responsible for cases of cancer recurrence. In this study,
      we report the presence of previously unknown populations of trophoblastic stem
      like cells (SLCs) that are resistant to the chemotherapeutic drug doxorubicin. We
      demonstrate that these populations express the stem cell markers NANOG and Sox2
      and higher levels of OCT-4 (NANOG+/OCT-4high/SOX2+). Although chemoresistant, we
      show that the invasive capacity of these trophoblastic SLCs is significantly
      inhibited by doxorubicin treatment. To better characterise these populations, we
      also identified cellular pathways that are involved in SLCs-chemoresistance to
      doxorubicin. In summary, we provide evidence of the presence of NANOG+/OCT
      4+/SOX2+ trophoblastic SLCs that are capable to contribute to the susceptibility
      to GTD and that may be involved in Chemoresistance associated with drug
      resistance and recurrence in high risk GTDs' patients. We propose that targeting
      these populations could be therapeutically exploited for clinical benefit.

PMID- 29467950
TI  - Genetic polymorphisms in HLA-DP and STAT4 are associated with IgA nephropathy in
      a Southwest Chinese population.
AB  - IgA nephropathy (IgAN) is the most common chronic glomerular disease worldwide.
      Genetic factors are thought to be crucial in the pathogenesis of IgAN. However,
      few data are available on the relationship between human leucocyte antigen (HLA)
      and signal transducer and activator of transcription 4 (STAT4) polymorphisms and
      IgAN susceptibility in the Chinese population. Therefore, we examined HLA-DP/DQ
      and STAT4 polymorphisms (rs3077, rs9277535, rs7453920 and rs7574865) in a total
      of 630 subjects including 140 IgAN and 490 healthy controls in Chinese. There
      were significant associations between IgAN patients and healthy controls in the
      allele frequency of rs3077, rs9277535 and rs7574865. In addition, the genotypes
      of rs3077, rs9277535 and rs7574865 were also significantly associated with IgAN
      under recessive models. Moreover, the haplotypes block AAG, AGG, GAG and GGA in
      the HLA gene significantly correlated with the risk of IgAN. This is the first
      study demonstrating the significant associations of SNP rs3077, rs9277535 and
      rs7574865 and the haplotypes in the HLA gene with the risk of IgAN in a Southwest
      Chinese population. This research provides a new insight into the significant
      relationship between HLA-DP and STAT4 polymorphisms and the susceptibility to
      IgAN.

PMID- 29467951
TI  - Reverting iodine avidity of radioactive-iodine refractory thyroid cancer with a
      new tyrosine kinase inhibitor (K905-0266) excavated by high-throughput NIS
      (sodium iodide symporter) enhancer screening platform using dual reporter gene
      system.
AB  - Radioactive-iodine (RAI) therapy is typically unprevailing as anaplastic thyroid
      cancer (ATC) management, owing to the decrease in the endogenous sodium iodide
      symporter (NIS) expression. Therefore, new strategies for NIS re-induction are
      required to improve the efficacy of RAI therapy in ATC. In this study, we
      developed a novel high-throughput NIS enhancer screening platform using a dual
      reporter gene system to identify a potent tyrosine kinase inhibitor (TKI) and
      selected a new hit compound, K905-0266 TKI. The effects of K905-0266 TKI
      treatment was validated as RAI accumulation, changes in signalling pathway
      related to thyroid pathogenesis, and cytotoxicity of RAI depending on re
      induction of endogenous NIS expression in ATC. Furthermore, we evaluated
      enhancement of NIS promoter and therapeutic efficacy of RAI in ATC tumour
      xenograft mice. After K905-0266 TKI treatment, the expression of endogenous NIS
      was significantly increased, while phosphorylated-ERK was decreased. In addition,
      the thyroid-metabolising protein expressions were upregulated and increased of
      RAI accumulation and its therapeutic effects in ATC. Moreover, K905-0266 TKI
      increased therapeutic efficacy of RAI in ATC tumour in vivo. In conclusion, we
      successfully established a novel high-throughput NIS enhancer screening platform
      to excavate a NIS enhancer and identified K905-0266 TKI among TKI candidates and
      it's proven to increase the endogenous NIS expression and therapeutic efficacy of
      RAI in ATC. These findings suggest that a novel high-throughput NIS enhancer
      screening platform is useful for selecting of NIS promoter enhancers. In
      addition, K905-0266 TKI can be used to re-induce endogenous NIS expression and
      recover RAI therapy in ATC.

PMID- 29467952
TI  - Diffusion-weighted imaging in identifying breast cancer pathological response to
      neoadjuvant chemotherapy: A meta-analysis.
AB  - Background: Diffusion-weighted imaging (DWI) is increasingly used to identify
      pathological complete responses (pCRs) to neoadjuvant chemotherapy (NAC) in
      breast cancer. The aim of the present study was to assess the utility of DWI
      using a pooled analysis. Materials and Methods: Literature databases were
      searched prior to July 2017. Fifteen studies with a total of 1181 patients were
      included. The data were extracted to perform pooled analysis, heterogeneity
      testing, threshold effect testing, sensitivity analysis, publication bias
      analysis and subgroup analyses. Result: The methodological quality was moderate.
      Remarkable heterogeneity was detected, primarily due to a threshold effect. The
      pooled weighted values were a sensitivity of 0.88 (95% confidence interval (CI):
      0.81, 0.92), a specificity of 0.79 (95% CI: 0.70, 0.86), a positive likelihood
      ratio of 4.1 (95% CI: 2.9, 5.9), a negative likelihood ratio of 0.16 (95% CI:
      0.10, 0.24), and a diagnostic odds ratio of 26 (95% CI: 15, 46). The area under
      the receiver operator characteristic curve was 0.91 (95% CI: 0.88, 0.93). In the
      subgroup analysis, the pooled specificity of change in the apparent diffusion
      coefficient (ADC) subgroup was higher than that in the pre-treatment ADC subgroup
      (0.80 [95% CI: 0.71, 087] vs. 0.63 [95% CI: 0.52, 0.73], P = 0.027). Conclusions:
      DWI may be an accurate and nonradioactive imaging technique for identifying pCRs
      to NAC in breast cancer. Nonetheless, there are a variety of issues when
      assessing DWI techniques for estimating breast cancer responses to NAC, and large
      scale and well-designed clinical trials are needed to assess the technique's
      diagnostic value.

PMID- 29467953
TI  - Meta-analysis of a 10-plex urine-based biomarker assay for the detection of
      bladder cancer.
AB  - A 10-plex urine-based bladder cancer (BCa) diagnostic signature has the potential
      to non-invasively predict the presence of BCa in at-risk patients, as reported in
      various case-control studies. The present meta-analysis was performed to re
      evaluate and demonstrate the robustness and consistency of the diagnostic utility
      of the 10-plex urine-based diagnostic assay. We re-analyzed primary data
      collected in five previously published case-control studies on the 10-plex
      diagnostic assay. Studies reported the sensitivity and specificity of ten urinary
      protein biomarkers for the detection of BCa, including interleukin 8, matrix
      metalloproteinases 9 and 10, angiogenin, apolipoprotein E, syndecan 1, alpha-1
      antitrypsin, plasminogen activator inhibitor-1, carbonic anhydrase 9, and
      vascular endothelial growth factor A. Data were extracted and reviewed
      independently by two investigators. Log odds ratios (ORs) were calculated to
      determine how strongly the 10-plex biomarker panel and individual biomarkers are
      associated with the presence of BCa. Data pooled from 1,173 patients were
      analyzed. The log OR for each biomarker was improved by 1.5 or greater with
      smaller 95% CI in our meta-analysis of the overall cohort compared with each
      analysis of an individual cohort. The combination of the ten biomarkers showed a
      higher log OR (log OR: 3.46, 95% CI: 2.60-4.31) than did any single biomarker
      irrespective of histological grade or disease stage of tumors. We concluded that
      the 10-plex BCa-associated diagnostic signature demonstrated a higher potential
      to identify BCa when compared to any single biomarker. Our results justify
      further advancement of the 10-plex protein-based diagnostic signature toward
      clinical application.

PMID- 29467954
TI  - Efficacy and safety of thrombopoietin receptor agonists in children with chronic
      immune thrombocytopenia: a meta-analysis.
AB  - Background and Aim: Thrombopoietin receptor agonists (TPO-RAs) have been shown to
      be safe and effective for adults with chronic immune thrombocytopenia (ITP). The
      aim of this meta-analysis is to assess the efficacy and safety of thrombopoietin
      receptor agonists for children with chronic ITP. Materials and Methods: Clinical
      randomized controlled trials (RCTs) evaluating the efficacy and safety of TPO-RAs
      in pediatric ITP patients published up to June 2017 were retrieved from PubMed,
      Cochrane Library, and Embase databases. Relevant data were extracted, and the
      Physiotherapy Evidence Database scale was used to assess the methodological
      quality. Stata/SE 12.0 was used to perform a meta-analysis. Results: Seven RCTs
      were included, with 238 patients and 107 patients in the TPO-RA group and the
      control group, respectively. Assessing efficacy, better results were found in the
      TPO-RA group for the rate of overall platelet response, durable response, and
      rescue medication needed. Furthermore, the TPO-RA group yielded superior results
      in the incidence of clinically significant bleeding events but had a comparable
      result in the incidence of any bleeding events and severe bleeding events. No
      significant difference was found between the two groups in health-related quality
      of life and parental burden. Assessing safety, no significant difference was
      found between the two groups in the incidence of any adverse events and severe
      adverse events. Conclusions: TPO-RAs are effective and safe agents for the
      treatment of chronic ITP in pediatric patients. Eltrombopag appears to be better
      than romiplostim in terms of the rate of rescue medication needed and clinically
      significant bleeding events.

PMID- 29467955
TI  - Milk/dairy products consumption and gastric cancer: an update meta-analysis of
      epidemiological studies.
AB  - The relationship between dairy consumption and gastric cancer risk has not been
      well studied. We therefore performed a update meta-analysis to evaluate the
      relationship. Published cohort and case-control studies were identified via
      computer searches and reviewing the reference lists of the key articles. Random
      effects meta-analysis was used to pool effects from 5 cohort and 29 case-control
      studies. The odds ratio for the overall association between dairy consumption and
      gastric cancer was 1.20 (95%confidence interval: 1.04-1.39). The combined risk
      estimate was similar for population-based case-control studies (odds ratio =
      1.27, 95%confidence interval: 1.00-1.61), but was reduced for hospital-based
      studies (odds ratio = 1.22; 95%confidence interval: 0.95-1.57) and cohort studies
      (odds ratio = 0.99; 95%confidence interval: 0.77-1.28). There was high
      heterogeneity in overall analyses. In the population-based subgroup analyses, the
      odds ratio was 0.96 (95%confidence interval: 0.69-1.34) when considering five
      studies assessing exposure two or more years before interview, and the
      association strengthened (odds ratio = 1.91, 95%confidence interval: 1.60-2.28)
      when dairy consumption was evaluated one year or less prior to interview. In
      conclusion, we found adverse effect of dairy consumption associated with gastric
      cancer.

PMID- 29467956
TI  - Vitamin D receptor Taq I polymorphism and the risk of prostate cancer: a meta
      analysis.
AB  - Numerous previous studies reported the association of Vitamin D receptor gene Taq
      Ipolymorphism with prostate cancer risk, however these results were
      controversial. In order to provide a relatively comprehensive description of this
      relationship, we conducted this meta-analysis by searching PubMed, Embase, and
      China National Knowledge Infrastructure. Finally, 36 studies with 8,423 cases and
      8,887 controls were included. Taq I polymorphism was found to marginally increase
      the prostate cancer risk in recessive genetic model (tt/Tt vs. TT: Odds Ratio
      (OR) = 0.89, 95% Confidence Interval (CI) = 0.80-1.00, p = 0.05) and allele
      genetic model (t vs. T allele: OR = 0.91, 95% CI = 0.84-0.99, p = 0.003) in the
      overall analysis. Subgroup analyses showed that significant increased risk was
      found in Asians in homozygote model (tt vs. TT: OR = 0.63, 95% CI = 0.41-0.95, p
      = 0.029) and allele genetic model (t vs. T: OR = 0.78, 95% CI = 0.67-0.90, p =
      0.002), and in the subgroup of population-based controls in all the genetic
      models. These results suggest that Taq Ipolymorphism might be a risk factor of
      prostate cancer risk, especially in Asians. It could be considered as a promising
      target to predict the prostate cancer risk for clinical practice.

PMID- 29467957
TI  - Gemcitabine-based chemotherapy as a viable option for treatment of advanced
      breast cancer patients: a meta-analysis and literature review.
AB  - This meta-analysis was designed to compare the efficacy and safety of gemcitabine
      based regimens for the treatment advanced breast cancer (ABC). Altogether 15
      studies involving 8195 ABC patients were retrieved for analysis. Compared with
      non-gemcitabine-based chemotherapies, patients receiving gemcitabine-based
      therapy exhibited better overall survival (OS), progression free survival (PFS),
      and objective response rate (ORR) (HR = 1.12, 95% CI 1.05 to 1.19; HR = 1.16, 95%
      CI 1.03 to 1.30; HR = 1.14, 95% CI 1.04 to 1.24). Grade 3/4 hematologic toxicity
      was significantly high but manageable in gemcitabine-based groups. Subgroup
      analysis revealed that patients with first-line gemcitabine-based chemotherapy
      had better OS (HR = 1.19, 95% CI 1.07 to 1.32), PFS (HR = 1.17, 95% CI 1.08 to
      1.27), and ORR (RR = 1.16, 95% CI 1.02 to 1.32). In addition, additional
      gemcitabine chemotherapy also showed better OS (HR = 1.17, 95% CI 1.06 to 1.30),
      PFS (HR = 1.20, 95% CI 1.11 to 1.30) and ORR (RR = 1.23, 95% CI 1.06 to 1.42)
      than gemcitabine replacement therapy. Furthermore, patients receiving gemcitabine
      taxanes-based regimens had better OS (HR = 1.17, 95% CI 1.06 to 1.28), PFS (HR =
      1.12, 95% CI 1.04 to 1.20) and ORR (RR = 1.17, 95% CI 1.01 to 1.35) than patients
      with non-gemcitabine-taxanes-based chemotherapy. These findings indicate that
      gemcitabine combination regimens could serve as a promising regimen for ABC
      patients, though increased hematologic toxicity should be considered with
      caution.

PMID- 29467958
TI  - Pharmacokinetic properties of radiolabeled mutant Interleukin-2v: a PET imaging
      study.
AB  - Interleukin-2 (IL2) is a cytokine that can stimulate cytotoxic immune cells to
      attack infected and malignant cells. Unfortunately, IL2 can also cause serious
      immune-related toxicity. Recently, a mutant of IL2 (IL2v) with abolished CD25
      binding, increased plasma half-life and less toxicity was engineered. Unlike wild
      type IL2 (wt-IL2), mutant IL2v does not bind to the alpha-subunit (CD25) of the
      high affinity IL2alphabetagamma receptor, but only to its beta and gamma subunit.
      Here, we investigated the biological properties of IL2v and compared with the wt
      IL2 using fluorine-18 and PET. [18F]FB-IL2v binds specifically to IL2 receptors
      (IL2R) on activated human peripheral blood monocytes (hPBMCs) and is cleared
      mainly by the kidneys (Balb/c mice). [18F]FB-IL2v PET studies in SCID mice
      injected with hPBMCs revealed high uptake in the implant (0.85 +/- 0.15 SUV),
      which was significantly reduced after pretreatment with wt-IL2 or mutant IL2v
      (SUV 0.26 +/- 0.1 and 0.46 +/- 0.1, p < 0.01). Compartment modeling and Logan
      graphical analysis in wistar rats inoculated with hPBMCs indicated that the
      binding of [18F]FB-IL2v to IL2R was reversible. The volume of distribution (VT)
      and the non-displaceable binding potential (BPnd) of mutant [18F]FB-IL2v in the
      implant were approximately 3 times lower than those of wild-type [18F]FB-IL2 (p <
      0.01). Pretreatment with wt-IL2 significantly reduced the VT and BPnd of mutant
      [18F]FB-IL2v in the implant (p < 0.001). This demonstrates that wild-type [18F]FB
      IL2 binds stronger to IL2R and has faster kinetics than [18F]FB-IL2v, which makes
      it less suitable as a therapeutic drug. [18F]FB-IL2v, on the other hand, seems to
      have better properties for use as a therapeutic drug.

PMID- 29467959
TI  - Apatinib as a third- or further- line treatment in patients with advanced NSCLC
      harboring wild-type EGFR.
AB  - Objectives: This study was conducted to evaluate the efficacy and safety of
      apatinib in advanced NSCLC patients with EGFR wild-type who have failed more than
      second-line chemotherapy. Materials and Methods: We retrospectively analyzed
      patients with EGFR wild-type advanced NSCLC who were treated with apatinib from
      January 2014 to August 2016. Objective response rate (ORR), disease control rate
      (DCR), progression free survival (PFS), overall survival (OS), and adverse events
      (AEs) were reveiwed and evaluated. Univariate and multivariate analyses were
      performed to determine the prognostic factors. Results: 36 patients were
      evaluable for safety and efficacy. 6 patients obtained partial response, and 21
      showed stable disease. The ORR and DCR were 16.7% and 75%, respectively. The
      median PFS and OS were 4.5 months and 8.2 months, respectively. Prognostic
      variable for a longer OS was good performance status (p = 0.015). Most adverse
      reactions were mild or moderate. Conclusions: Apatinib should be recommended as a
      third- or further- line therapy in advanced NSCLC patients with EGFR wild-type
      due to its better efficacy and tolerable toxicity.

PMID- 29467960
TI  - A liquid biopsy for bronchopulmonary/lung carcinoid diagnosis.
AB  - No effective blood biomarker exists to detect and clinically manage
      bronchopulmonary (BP) neuroendocrine tumors (NET). We developed a blood-based 51
      NET-specific transcript set for diagnosis and monitoring and evaluated clinical
      performance metrics. It accurately diagnosed the tumor and differentiated stable
      from progressive disease as determined by RECIST criteria. Gene expression was
      evaluated in: a) publicly available BPNET transcriptomes (GSE35679); b) two BPNET
      cell-lines; and c) BPNET tissue with paired blood (n = 7). Blood gene expression
      was assessed in 194 samples including controls, benign lung diseases, malignant
      lung diseases and small bowel NETs. A separate validation study in 25 age- and
      gender-matched BPNETs/controls was performed. Gene expression measured by real
      time PCR was scored (0-100%; normal: < 14%). Regression analyses, Principal
      Component Analysis (PCA), hierarchical clustering, Fisher's and non-parametric
      evaluations were undertaken. All 51 genes were identified in BPNET
      transcriptomes, tumor samples and cell-lines. Significant correlations were
      evident between paired tumor and blood (R2:0.63-0.91, p < 0.001). PCA and
      hierarchical clustering identified blood gene expression was significantly
      different between lung cancers and benign diseases, including BPNETs. Gene
      expression was highly correlated (R2: 0.91, p = 1.7 * 10-15) between small bowel
      and BPNET. For validation, all 25 BPNETs were positive compared to 20% controls
      (p < 0.0001). Scores were significantly elevated (p < 0.0001) in BPNETs (57 +/-
      28%) compared to controls (4 +/- 5%). BPNETs with progressive disease (85 +/-
      11%) exhibited higher scores than stable disease (32 +/- 7%, p < 0.0001). Blood
      measurements accurately diagnosed bronchopulmonary carcinoids, distinguishing
      stable from progressive disease. This marker panel will have clinical utility as
      a diagnostic liquid biopsy able to define disease activity and progression in
      real-time.

PMID- 29467961
TI  - The outcomes and prognostic factors of acute respiratory failure in the patients
      90 years old and over.
AB  - This retrospective cohort study investigated the outcomes and prognostic factors
      in nonagenarians (patients 90 years old or older) with acute respiratory failure.
      Between 2006 and 2016, all nonagenarians with acute respiratory failure requiring
      invasive mechanical ventilation (MV) were enrolled. Outcomes including in
      hospital mortality and ventilator dependency were measured. A total of 173
      nonagenarians with acute respiratory failure were admitted to the intensive care
      unit (ICU). A total of 56 patients died during the hospital stay and the rate of
      in-hospital mortality was 32.4%. Patients with higher APACHE (Acute Physiology
      and Chronic Health Evaluation) II scores (adjusted odds ratio [OR], 5.91; 95 %
      CI, 1.55-22.45; p = 0.009, APACHE II scores >= 25 vs APACHE II scores < 15), use
      of vasoactive agent (adjust OR, 2.67; 95% CI, 1.12-6.37; p = 0.03) and more organ
      dysfunction (adjusted OR, 11.13; 95% CI, 3.38-36.36, p < 0.001; >= 3 organ
      dysfunction vs <= 1 organ dysfunction) were more likely to die. Among the 117
      survivors, 25 (21.4%) patients became dependent on MV. Female gender (adjusted
      OR, 3.53; 95% CI, 1.16-10.76, p = 0.027) and poor consciousness level (adjusted
      OR, 4.98; 95% CI, 1.41-17.58, p = 0.013) were associated with MV dependency. In
      conclusion, the mortality rate of nonagenarians with acute respiratory failure
      was high, especially for those with higher APACHE II scores or more organ
      dysfunction.

PMID- 29467962
TI  - Inflammatory responses and inflammation-associated diseases in organs.
AB  - Inflammation is a biological response of the immune system that can be triggered
      by a variety of factors, including pathogens, damaged cells and toxic compounds.
      These factors may induce acute and/or chronic inflammatory responses in the
      heart, pancreas, liver, kidney, lung, brain, intestinal tract and reproductive
      system, potentially leading to tissue damage or disease. Both infectious and non
      infectious agents and cell damage activate inflammatory cells and trigger
      inflammatory signaling pathways, most commonly the NF-kappaB, MAPK, and JAK-STAT
      pathways. Here, we review inflammatory responses within organs, focusing on the
      etiology of inflammation, inflammatory response mechanisms, resolution of
      inflammation, and organ-specific inflammatory responses.

PMID- 29467964
TI  - Correction: Co-targeting translation and proteasome rapidly kills colon cancer
      cells with mutant RAS/RAF via ER stress.
AB  - [This corrects the article DOI: 10.18632/oncotarget.14063.].

PMID- 29467965
TI  - A Toolkit for Medical Education Scholarship.

PMID- 29467966
TI  - Addressing a Gender Identity Crisis in Medicine.

PMID- 29467967
TI  - What Should I Do With My Student Loans? A Proposed Strategy for Educational Debt
      Management.

PMID- 29467968
TI  - Continuity of Care in Resident Outpatient Clinics: A Scoping Review of the
      Literature.
AB  - Background : Continuity between patients and physicians is a core principle of
      primary care and an accreditation requirement. Resident continuity clinics face
      challenges in nurturing continuity for their patients and trainees. Objective :
      We undertook a scoping review of the literature to better understand published
      benchmarks for resident continuity; the effectiveness of interventions to improve
      continuity; and the impact of continuity on resident and patient satisfaction,
      patient outcomes, and resident career choice. Methods : We developed a MEDLINE
      search strategy to identify articles that defined continuity in residency
      programs in internal medicine, family medicine, and pediatrics published prior to
      December 31, 2015, and used a quality evaluation tool to assess included studies.
      Results : The review includes 34 articles describing 12 different measures of
      continuity. The usual provider of care and continuity for physician formulas were
      most commonly utilized, and mean baseline continuity was 56 and 55, respectively
      (out of a total possible score of 100). Clinic and residency program redesign
      innovations (eg, advanced access scheduling, team-based care, and block
      scheduling) were studied and had mixed impact on continuity. Continuity in
      resident clinics is lower than published continuity rates for independently
      practicing physicians. Conclusions : Interventions to enhance continuity in
      resident clinics have mixed effects. More research is needed to understand how
      changes in continuity affect resident and patient satisfaction, patient outcomes,
      and resident career choice. A major challenge to research in this area is the
      lack of empanelment of residents' patients, creating difficulties in scheduling
      and measuring continuity visits.

PMID- 29467970
TI  - Recovery From the Burnout Epidemic: How the Academic Community Can Help
      (Commentary).

PMID- 29467969
TI  - "It's Not Just Time Off": A Framework for Understanding Factors Promoting
      Recovery From Burnout Among Internal Medicine Residents.
AB  - Background : Burnout rates for internal medicine residents are among the highest
      of all specialties, yet little is known about how residents recover from burnout.
      Objective : We identified factors promoting recovery from burnout and factors
      that assist with the subsequent avoidance of burnout among internal medicine
      residents. Methods : A purposive sample of postgraduate year 2 (PGY-2), PGY-3,
      and recent graduates who experienced and recovered from burnout during residency
      participated in semistructured, 60-minute interviews from June to August 2016.
      Using qualitative methods derived from grounded theory, saturation of themes
      occurred after 25 interviews. Coding was performed in an iterative fashion and
      consensus was reached on major themes. Results : Coding revealed 2 different
      categories of resident burnout-circumstantial and existential-with differing
      recovery and avoidance methods. Circumstantial burnout stemmed from self-limited
      circumstances and environmental triggers. Recovery from, and subsequent avoidance
      of, circumstantial burnout arose from (1) resolving workplace challenges; (2)
      nurturing personal lives; and (3) taking time off. In contrast, existential
      burnout stemmed from a loss of meaning in medicine and an uncertain professional
      role. These themes were identified around recovery: (1) recognizing burnout and
      feeling validated; (2) connecting with patients and colleagues; (3) finding
      meaning in medicine; and (4) redefining a professional identity and role.
      Conclusions : Our study suggests that residents experience different types of
      burnout and have variable methods by which they recover from and avoid further
      burnout. Categorizing residents' burnout into circumstantial versus existential
      experiences may serve as a helpful framework for formulating interventions.

PMID- 29467971
TI  - JGME-ALiEM Hot Topics in Medical Education: An Analysis of a Virtual Discussion
      on Resident Well-Being.
AB  - Background : Physician well-being is garnering increasing attention. In 2016, the
      Journal of Graduate Medical Education (JGME) published a review by Kristin Raj,
      MD, entitled "Well-Being in Residency: A Systematic Review." There is benefit in
      contextualizing the literature on resident well-being through an academic journal
      club. Objective : We summarized an asynchronous, online journal club discussion
      about this systematic review and highlighted themes that were identified in the
      review. Methods : In January 2017, JGME and the Academic Life in Emergency
      Medicine (ALiEM) blog facilitated an open-access, online, weeklong journal club
      on the featured JGME article. Online discussions and interactions were
      facilitated via blog posts and comments, a video discussion on Google Hangouts on
      Air, and Twitter. We performed a thematic analysis of the discussion and captured
      web analytics. Results : Over the first 14 days, the blog post was viewed 1070
      unique times across 52 different countries. A total of 130 unique participants on
      Twitter posted 480 tweets using the hashtag #JGMEscholar. Thematic analysis
      revealed 5 major domains: the multidimensional nature of well-being, measurement
      of well-being, description of wellness programs and interventions, creation of a
      culture of wellness, and critique of the methodology of the review. Conclusions :
      Our online journal club highlighted several gaps in the current understanding of
      resident well-being, including the need for consensus on the operational
      definition, the need for effective instruments to evaluate wellness programs and
      identify residents in distress, and a national research collaboration to assess
      wellness programs and their impact on resident well-being.

PMID- 29467972
TI  - A Qualitative Analysis of Attending Physicians' Use of Shared Decision-Making:
      Implications for Resident Education.
AB  - Background : Physicians need to rapidly and effectively facilitate patient
      centered, shared decision-making (SDM) conversations, but little is known about
      how residents or attending physicians acquire this skill. Objective : We explored
      emergency medicine (EM) attending physicians' use of SDM in the context of their
      experience as former residents and current educators and assessed the
      implications of these findings on learning opportunities for residents. Methods :
      We used semistructured interviews with a purposeful sample of EM physicians.
      Interviews were transcribed verbatim, and 3 research team members performed
      iterative, open coding of transcripts, building a provisional codebook as work
      progressed. We analyzed the data with a focus on participants' acquisition and
      use of skills required for SDM and their use of SDM in the context of resident
      education. Results : Fifteen EM physicians from academic and community practices
      were interviewed. All reported using SDM techniques to some degree. Multiple
      themes noted had negative implications for resident acquisition of this skill:
      (1) the complex relationships among patients, residents, and attending
      physicians; (2) residents' skill levels; (3) the setting of busy emergency
      departments; and (4) individual attending factors. One theme was noted to
      facilitate resident education: the changing culture-with a cultural shift toward
      patient-centered care. Conclusions : A constellation of factors may diminish
      opportunities for residents to acquire and practice SDM skills. Further research
      should explore residents' perspectives, address the modifiable obstacles
      identified, and examine whether these issues generalize to other specialties.

PMID- 29467973
TI  - A Descriptive Analysis of the Use of Twitter by Emergency Medicine Residency
      Programs.
AB  - Background : Twitter is increasingly recognized as an instructional tool by the
      emergency medicine (EM) community. In 2012, the Council of Residency Directors in
      Emergency Medicine (CORD) recommended that EM residency programs' Twitter
      accounts be managed solely by faculty. To date, little has been published
      regarding the patterns of Twitter use by EM residency programs. Objective : We
      analyzed current patterns in Twitter use among EM residency programs with
      accounts and assessed conformance with CORD recommendations. Methods : In this
      mixed methods study, a 6-question, anonymous survey was distributed via e-mail
      using SurveyMonkey. In addition, a Twitter-based search was conducted, and the
      public profiles of EM residency programs' Twitter accounts were analyzed. We
      calculated descriptive statistics and performed a qualitative analysis on the
      data. Results : Of 168 Accreditation Council for Graduate Medical Education
      accredited EM programs, 88 programs (52%) responded. Of those programs, 58% (51
      of 88) reported having a program-level Twitter account. Residents served as
      content managers for those accounts in the majority of survey respondents (61%,
      28 of 46). Most programs did not publicly disclose the identity or position of
      their Twitter content manager. We found a wide variety of applications for
      Twitter, with EM programs most frequently using Twitter for educational and
      promotional purposes. There is significant variability in the numbers of
      followers for EM programs' Twitter accounts. Conclusions : Applications and usage
      among EM residency programs are varied, and are frequently not consistent with
      current CORD recommendations.

PMID- 29467963
TI  - New extracellular factors in glioblastoma multiforme development: neurotensin,
      growth differentiation factor-15, sphingosine-1-phosphate and cytomegalovirus
      infection.
AB  - Recent years have seen considerable progress in understanding the biochemistry of
      cancer. For example, more significance is now assigned to the tumor
      microenvironment, especially with regard to intercellular signaling in the tumor
      niche which depends on many factors secreted by tumor cells. In addition, great
      progress has been made in understanding the influence of factors such as
      neurotensin, growth differentiation factor-15 (GDF-15), sphingosine-1-phosphate
      (S1P), and infection with cytomegalovirus (CMV) on the 'hallmarks of cancer' in
      glioblastoma multiforme. Therefore, in the present work we describe the influence
      of these factors on the proliferation and apoptosis of neoplastic cells, cancer
      stem cells, angiogenesis, migration and invasion, and cancer immune evasion in a
      glioblastoma multiforme tumor. In particular, we discuss the effect of
      neurotensin, GDF-15, S1P (including the drug FTY720), and infection with CMV on
      tumor-associated macrophages (TAM), microglial cells, neutrophil and regulatory T
      cells (Treg), on the tumor microenvironment. In order to better understand the
      role of the aforementioned factors in tumoral processes, we outline the latest
      models of intratumoral heterogeneity in glioblastoma multiforme. Based on the
      most recent reports, we discuss the problems of multi-drug therapy in treating
      glioblastoma multiforme.

PMID- 29467974
TI  - Stroke Simulation Improves Acute Stroke Management: A Systems-Based Practice
      Experience.
AB  - Background : Literature on the effectiveness of simulation-based medical
      education programs for caring for acute ischemic stroke (AIS) patients is
      limited. Objective : To improve coordination and door-to-needle (DTN) time for
      AIS care, we implemented a stroke simulation training program for neurology
      residents and nursing staff in a comprehensive stroke center. Methods : Acute
      stroke simulation training was implemented for first-year neurology residents in
      July 2011. Simulations were standardized using trained live actors, who portrayed
      stroke vignettes in the presence of a board-certified vascular neurologist. A
      debriefing of each resident's performance followed the training. The hospital
      stroke registry was also used for retrospective analysis. The study population
      was defined as all patients treated with intravenous tissue plasminogen activator
      for AIS between October 2008 and September 2014. Results : We identified 448
      patients meeting inclusion criteria. Simulation training independently predicted
      reduction in DTN time by 9.64 minutes (95% confidence interval [CI] -15.28 to 
      4.01, P = .001) after controlling for age, night/day shift, work week versus
      weekend, and blood pressure at presentation (> 185/110). Systolic blood pressure
      higher than 185 was associated with a 14.28-minute increase in DTN time (95% CI
      3.36-25.19, P = .011). Other covariates were not associated with any significant
      change in DTN time. Conclusions : Integration of simulation based-medical
      education for AIS was associated with a 9.64-minute reduction in DTN time.

PMID- 29467975
TI  - Implementing a Universal Well-Being Assessment to Mitigate Barriers to Resident
      Utilization of Mental Health Resources.
AB  - Background : Physician utilization of well-being resources remains low despite
      efforts to promote use of these resources. Objective : We implemented a well
      being assessment for internal medicine residents to improve access and use of
      mental health services. Methods : We scheduled all postgraduate year 1 (PGY-1)
      and PGY-2 residents at West Virginia University for the assessment at our faculty
      and staff assistance program (FSAP). While the assessment was intended to be
      universal (all residents), we allowed residents to "opt out." The assessment
      visit consisted of an evaluation by a licensed therapist, who assisted residents
      with a wellness plan. Anonymous surveys were distributed to all residents, and
      means were compared by Student's t test. Results : Thirty-eight of 41 PGY-1 and
      PGY-2 residents (93%) attended the scheduled appointments. Forty-two of 58
      residents (72%, including PGY-3s) completed the survey. Of 42 respondents, 28
      (67%) attended the assessment sessions, and 14 (33%) did not. Residents who
      attended the sessions gave mean ratings of 7.8 for convenience (1, not
      convenient, to 9, very convenient), and 7.9 for feeling embarrassed if colleagues
      knew they attended (1, very embarrassed, to 9, not embarrassed). Residents who
      attended the assessment sessions reported they were more likely to use FSAP
      services in the future, compared with those who did not attend (P < .001).
      Conclusions : Offering residents a well-being assessment may have mitigated
      barriers to using counseling resources. The majority of residents who
      participated had a positive view of the program and indicated they would return
      to FSAP if they felt they needed counseling.

PMID- 29467976
TI  - Improving Resident Use of Mental Health Resources: It's Time for an Opt-Out
      Strategy to Address Physician Burnout and Depression (Commentary).

PMID- 29467977
TI  - myTIPreport and Training for Independent Practice: A Tool for Real-Time Workplace
      Feedback for Milestones and Procedural Skills.
AB  - Background : Few tools currently exist for effective, accessible delivery of real
      time, workplace feedback in the clinical setting. Objective : We developed and
      implemented a real-time, web-based tool for performance-based feedback in the
      clinical environment. Methods : The tool (myTIPreport) was designed for
      performance-based feedback to learners on the Accreditation Council for Graduate
      Medical Education (ACGME) Milestones and procedural skills. "TIP" stands for
      "Training for Independent Practice." We implemented myTIPreport in obstetrics and
      gynecology (Ob-Gyn) and female pelvic medicine and reconstructive surgery (FPMRS)
      programs between November 2014 and May 2015. Residents, fellows, teachers, and
      program directors completed preimplementation and postimplementation surveys on
      their perceptions of feedback. Results : Preimplementation surveys were completed
      by 656 participants of a total of 980 learners and teachers in 19 programs (12 Ob
      Gyn and 7 FPMRS). This represented 72% (273 of 378) of learners and 64% (383 of
      602) of teachers. Seventy percent of participants (381 of 546) reported having
      their own individual processes for real-time feedback; the majority (79%, 340 of
      430) described these processes as informal discussions. Over 6 months, one-third
      of teachers and two-thirds of learners used the myTIPreport tool a total of 4311
      times. Milestone feedback was recorded 944 times, and procedural feedback was
      recorded 3367 times. Feedback addressed all ACGME Milestones and procedures
      programmed into myTIPreport. Most program directors reported that tool
      implementation was successful. Conclusions : The majority of learners
      successfully received workplace feedback using myTIPreport. This web-based tool,
      incorporating procedures and ACGME Milestones, may be an important transition
      from other feedback formats.

PMID- 29467979
TI  - Programmatic Assessment in Emergency Medicine: Implementation of Best Practices.
AB  - Background : Programmatic assessment is the intentional collection of key data
      from multiple sources for both assessment of learning and assessment for
      learning. Objective : We developed a system of programmatic assessment (PA) to
      identify competency progression (summative) and assessment for learning to assist
      residents in their formative development. Methods : The programmatic assessment
      was designed iteratively from 2014 through 2016. All assessments were first
      categorized by competency domain and source of assessment. The number of
      assessment modalities for each competency domain was collected. These multisource
      assessments were then mapped by program leadership to the milestones to develop a
      master PA blueprint. A resident learning management system provided the platform
      for aggregating formative and summative data, allowing residents and faculty
      ongoing access to guide learning and assessment. A key component of programmatic
      assessment was to support resident integration of assessment information through
      feedback by faculty after shifts and during monthly formal assessments,
      semiannual resident reviews, and summative judgments by the Clinical Competency
      Committee. Results : Through the PA, the 6 competency domains are assessed
      through multiple modalities: patient care (22 different assessments),
      professionalism (18), systems-based practice (17), interprofessional and
      communication skills (16), medical knowledge (11), and practice-based learning
      and improvement (6). Each assessment provides feedback to the resident in various
      formats. Our programmatic assessment has been utilized for more than 2 years with
      iterative improvements. Conclusions : The implementation of programmatic
      assessment allowed our program to organize diverse, multisourced feedback to
      drive both formative and summative assessments.

PMID- 29467978
TI  - Feasibility of a Comprehensive Medical Knowledge Curriculum in Internal Medicine
      Using Team-Based Learning.
AB  - Background : Team-based learning (TBL) is an active learning strategy with
      descriptions of its use in resident education limited to pilot studies. Objective
      : We developed a comprehensive medical knowledge TBL curriculum for an internal
      medicine residency, and assessed feasibility. Methods : We developed a 135-topic
      TBL curriculum to replace a noon conference lecture series, and implemented it
      over a 3-year period (2013-2016). In this article we describe the planning,
      curricular design, faculty recruitment and development, and lesson structure. We
      assessed feasibility in terms of faculty participation, resident preparedness,
      resident and faculty satisfaction, and costs. Results : Most faculty initially
      were unfamiliar with TBL. Through faculty resource materials and flexible faculty
      development, participating faculty increased from 3 to 74. In a 2015 faculty
      survey (N = 64, 69% response rate), 73% (32 of 44) reported faculty development
      was adequate, 70% (31 of 44) indicated lesson preparation time reasonable, and
      95% (42 of 44) reported preparation materials were helpful. A 2016 resident
      survey (N = 89, 72% response rate) revealed that most residents completed reading
      assignments in advance, 78% (50 of 64) found readings manageable, and 77% (49 of
      64) felt they learned better from TBL compared to lectures. Costs included
      compensated time for 1 faculty TBL "champion" and an assistant. Conclusions :
      Implementing a comprehensive medical knowledge curriculum using TBL in an
      internal medicine residency was feasible, and resulted in high faculty acceptance
      and learner satisfaction. Departmental support of a TBL champion, flexible
      faculty development, and well-designed resource materials were determinants of
      success.

PMID- 29467980
TI  - A Prospective Multicenter Evaluation of the Value of the On-Call Orthopedic
      Resident.
AB  - Background : Funding for graduate medical education is at risk despite the
      services provided by residents. Objective : We quantified the potential monetary
      value of services provided by on-call orthopedic surgery residents. Methods : We
      conducted a prospective, cross-sectional, multicenter cohort study design. Over a
      90-day period in 2014, we collected data on consults by on-call orthopedic
      surgery residents at 4 tertiary academic medical centers in the United States.
      All inpatient and emergency department consults evaluated by first-call residents
      during the study period were eligible for inclusion. Based on their current
      procedural terminology codes, procedures and evaluations for each consult were
      assigned a relative value unit and converted into a monetary value to determine
      the value of services provided by residents. The primary outcome measures were
      the total dollar value of each consult and the percentage of resident salaries
      that could be funded by the generated value of the resident consult services.
      Results : In total, 2644 consults seen by 33 residents from the 4 institutions
      were included for analysis. These yielded an average value of $81,868 per center
      for the 90-day study period, that is, $327,471 annually. With a median resident
      stipend of $53,992, the extrapolated average percentage of resident stipends that
      could be funded by these consult revenues was 73% of the stipends of the
      residents who took call or 36% of the stipends of the overall resident cohort.
      Conclusions : The potential monetary value generated by on-call orthopedic
      surgery residents is substantial.

PMID- 29467981
TI  - Using Chart Review and Chart-Stimulated Recall for Resident Assessment.

PMID- 29467982
TI  - My 3 Rules.

PMID- 29467984
TI  - Top Reviewers 2017.

PMID- 29467983
TI  - Burnout and Wellness: Another Answer.

PMID- 29467985
TI  - Response to "The Dawn of Quantified Humanism".

PMID- 29467986
TI  - Redirecting the Focus of Resident Mentorship.

PMID- 29467987
TI  - Applying Feedback Lessons to Online Medical Question Banks.

PMID- 29467988
TI  - The Montefiore 10: A Pilot Curriculum in Point-of-Care Ultrasound for Internal
      Medicine Residency Training.

PMID- 29467989
TI  - Making the Case for an X + Y Scheduling Model in Preliminary Internal Medicine
      Residency Training.

PMID- 29467990
TI  - Improving the Improvement Process: 5 Dimensions of Effective Program Evaluation
      and Improvement.

PMID- 29467991
TI  - Understanding Iron Metabolism: Lessons from Transfusion-dependent Thalassemia.

PMID- 29467992
TI  - Obesity, An Enemy of Male Fertility: A Mini Review.
AB  - Obesity is a highly prevalent non-communicable disease worldwide and is commonly
      associated with male infertility. Several etiopathological theories have been
      mentioned in the literature by which obesity affects spermatogenesis, thus
      affecting the male fertility potential. Mechanisms for explaining the effect of
      obesity on male infertility include endocrinopathy, increased aromatization
      activity, associated erectile dysfunction, psychological and thermal effects,
      obstructive sleep apnea, increased leptin and oxygen free radicals, and
      associated inflammatory and obstructive elements of epididymitis. Treatment of
      such a complex problem includes weight reduction (by lifestyle modification and
      increased physical activity), optimization of altered testosterone-to-estradiol
      ratio using aromatase inhibitors and/or gonadotropins, treatment of associated
      comorbidities by phosphodiesterase inhibitors for erectile dysfunction, and
      insulin-sensitizing agents for the management of diabetes. The aim of this mini
      review is to highlight the pathological basis of this problem and to focus on
      obesity as an etiology of male infertility.

PMID- 29467993
TI  - Pediatric Renal Transplantation in Oman: A Single-center Experience.
AB  - Objectives: This study sought to report 22 years experience in pediatric kidney
      transplantation in Oman. Methods: Electronic charts of all Omani children below
      13 years of age who received a kidney transplant from January 1994 to December
      2015 were reviewed. Data collected included patient demographics, etiology of end
      stage kidney disease, modality and duration of dialysis, donor type, complication
      of kidney transplantation (including surgical complications, infections, graft
      rejection) graft and patient survival, and duration of follow-up. Results: During
      the study period transplantation from 27 living related donors (LRDs), 42 living
      unrelated donors (LURDs), also referred to as commercial transplant, and one
      deceased donor were performed. The median age at transplantation was nine years
      for both groups. The most common primary diagnosis was congenital anomalies of
      the kidney and urinary tract in 32.8% of patients followed by familial nephrotic
      syndrome in 20.0% and polycystic kidney disease in 18.5%. Almost half the
      patients were on hemodialysis before transplantation, 35.7% were on peritoneal
      dialysis, and 14.2% received preemptive renal transplantation. Children who
      received LURD kidneys had high surgical complications (42.8%) compared to the
      LRDs group (17.8%). Five patients from LURDs group had early graft nephrectomy
      and four patients developed non-graft function or delayed graft function. In
      addition, patients in the LURDs group had a higher incidence of hypertension and
      acute rejection. Graft and patient survival were both better in the LRDs than the
      LURDs group. Conclusions: Although our pediatric kidney transplant program is a
      young program it has had successful patient outcomes comparable to international
      programs. Our study provides evidence that in addition to legal and ethical
      issues with commercial transplant, it also carries significantly higher morbidity
      and reduced graft and patient survival.

PMID- 29467994
TI  - Neonatal and Obstetrical Outcomes of Pregnancies in Systemic Lupus Erythematosus.
AB  - Objectives: Systemic lupus erythematous (SLE) is a chronic autoimmune disease
      that affects women primarily of childbearing age. The objective of this study was
      to determine the neonatal and maternal outcomes of pregnancies in SLE patients
      compared to pregnancies in healthy controls. Methods: We conducted a
      retrospective cohort study in a tertiary care hospital in Oman between January
      2007 and December 2013. We analyzed 147 pregnancies and compared 56 (38.0%)
      pregnancies in women with SLE with 91 (61.9%) pregnancies in healthy control
      women. Disease activity was determined using the Systemic Lupus Erythematosus
      Disease Activity Index (SLEDAI). Results: The mean age of the cohort was 30.0+/
      5.0 years ranging from 19 to 44 years old. Patients with SLE were treated with
      hydroxychloroquine (n = 41; 73.2%), prednisolone (n = 38; 67.8%), and
      azathioprine (n = 17; 30.3%). There was no disease activity in 39.2% (n = 22) of
      patients while 41.0% (n = 23), 12.5% (n = 7), and 7.1% (n = 4) had mild (SLEDAI 1
      5), moderate (SLEDAI 6-10), and severe (SLEDAI 3 11) disease activity,
      respectively, at onset of pregnancy. Pregnancies in patients with SLE were
      associated with higher abortions (42.8% vs. 15.3%; p < 0.001), gestational
      diabetes (28.3% vs. 10.2%; p = 0.004), polyhydramnios (7.1% vs. 0.0%; p = 0.020),
      previous preterm pregnancies (8.9% vs. 1.0%; p = 0.030), and intrauterine growth
      retardation (21.4% vs. 0.0%; p < 0.001) when compared to pregnancies in healthy
      control women. Furthermore, the neonates born to mothers with SLE were more
      likely to be preterm (28.5% vs. 1.0%; p < 0.001), have a low birth weight (< 2
      500 g) (32.1% vs. 1.0%; p < 0.001), and were associated with stillbirth (7.1% vs.
      0.0%; p = 0.010) when compared to neonates born to healthy control mothers.
      Conclusions: Pregnancies in women with SLE were associated with higher neonatal
      and maternal complications. Therefore, pregnant women with SLE should have their
      pregnancy accurately planned, monitored, and managed according to a
      multidisciplinary treatment schedule.

PMID- 29467995
TI  - Transitional Female Sacrum: Dimensions, Alterations in Dorsal Pelvic Structure,
      and Potential Obstetric Implications.
AB  - Objectives: The space available within the female pelvis is determined by the
      morphology of all bony components constituting the pelvic skeleton. Although
      several studies have investigated the impact of hip-bone structural variations in
      on parturition, the potential effects of commonly occurring lumbosacral
      transitional vertebrae (LSTV) variations have been underreported. This
      descriptive morphometric study reports dimensions of the female sacrum associated
      LSTV variations and suggests their probable mechanistic effects on normal labor.
      Methods: One hundred and twelve female osteological sacral specimens with LSTV
      were examined for the type of transitional anomaly. Position, height, and surface
      areas of the auricular surfaces, interauricular distances, sacral heights, S1
      body width and upper surface areas, and articulating areas of S1 facets were
      measured and compared with data from non-transitional samples. Results: Female
      LSTV predominantly presented as accessory L5-S1 articulations (unilateral and
      bilateral) and degrees of lumbarization (separation of the first sacral segment).
      Since some of these alterations were found to be significantly associated with
      changes in sacral size, these features, in conjunction with cranial shift of the
      auricular surfaces, may be associated with overall in dorsal pelvic dimensions.
      Conclusions: Structural alterations identified in female LSTV sacrum may change
      dorsal pelvic dimensions and thus, the availability of dorsal pelvic space,
      potentially altering the biomechanics of normal labor.

PMID- 29467996
TI  - Strategic Approaches Towards Pertussis Control in Oman.
AB  - Objectives: Pertussis is a highly contagious disease that causes severe and
      serious symptoms among infants and young children with fatalities observed in
      early infancy. The disease is milder among adolescents and adults. In this paper,
      we describe the progress made towards pertussis control in Oman and the
      challenges ahead to achieve control and maintain it. Methods: Pertussis data were
      collected between 1981 and 2015 from various sources including Annual Health
      Reports, annual Ministry of Health progress reports, and Community Health and
      Diseases Surveillance Newsletter, which provided information for the calculation
      of different pertussis indicators. Results: Diphtheria-tetanus-whole cell
      pertussis 3 (DTwP3) vaccination coverage rose from 19% in 1981 to 97% in 1992 and
      has been at 3 97% until 2015. The overall incidence of pertussis dropped
      dramatically from an average of 771 cases per 100 000 population from 1981
      through 1985, to 21 cases per 100 000 population between 2011 and 2015 (p <
      0.001). Since 1987, pertussis cases were cyclical, with peaks every three to five
      years with three major outbreaks reported in some parts of the country. Between
      2011 and 2015, 831 cases were notified of which 785 (94.4%) met the pertussis
      case definition. Of these 785 cases, 625 (79.7%) were in children aged < 12
      months (average rate 185 per 100 000 population), and almost all were
      hospitalized. Of the 625, 357 (57.1%) were aged < 2 months (average incidence of
      600/100 000 population), 129 (20.6%) were 2-3 months old (average incidence of
      202/100 000 population), 80 (12.8%) were 4-6 months (average incidence of 119/100
      000 population), and 59 (9.4%) were 6-12 months old (average incidence is 22/100
      000 population). There were 160/785 (20.3%) cases reported in children 3 12
      months old (average rate 4/100 000 population). Downward trend rates were
      reported in the 5-14 year age group and a very low disease rate was observed in
      the > 15 years group. Since 2007, no deaths recorded were attributed to
      pertussis. Conclusions: Oman has a high coverage of DTP3; however, pertussis
      control remains a challenge among infants < 12 months old. Therefore, tetanus,
      diphtheria, and acellular pertussis (Tdap) vaccination of pregnant women is
      likely to be the best strategy for preventing the disease in infants.

PMID- 29467997
TI  - Investigation of Class I, II, and III Integrons Among Acinetobacter Baumannii
      Isolates from Hospitalized Patients in Isfahan, Iran.
AB  - Objectives: This study aimed to determine the prevalence of class I, II, and III
      integrons among clinical Acinetobacter baumannii isolates collected from
      hospitalized patients. Methods: This cross-sectional study was conducted at two
      teaching hospitals in Isfahan, Iran, from October 2015 to October 2016. A total
      of 147 non-duplicate A. baumannii isolates were collected from clinical specimens
      and identified as A. baumannii using standard microbiological methods and
      confirmed by genotyping. Antimicrobial susceptibility was determined using disc
      diffusion method, and the presence of integron genes was performed using the
      polymerase chain reaction. Results: Out of 147 confirmed A. baumannii isolates,
      97.3% of isolates were extensive drug-resistant (XDR) and 2.7% were multidrug
      resistant (MDR). Class I and II integrons were detected in 63.9% and 78.2% of the
      A. baumannii, respectively. Class III integron was not detected in any of the
      isolates. Conclusion: Our results show a high prevalence of classes I and II
      integrons which may play a key role in the acquisition of MDR and XDR phenotype
      among A. baumannii isolates in our region. Therefore, use of appropriate
      infection control in clinical settings and implementation of treatment strategies
      is necessary for our hospitals.

PMID- 29467998
TI  - Immunophenotypic Characteristics of T-Acute Lymphoblastic Leukemia in Omani
      Patients: A Correlation with Demographic Factors.
AB  - Objectives: To study and classify the immunophenotypic characteristics of Omani
      patients diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) and to
      correlate the results with age and gender as well as biological factors
      (peripheral and bone marrow blast cells percentage). Methods: Fifty cases from
      both genders and of all ages who fulfilled the inclusion criteria with a
      diagnosis of T-ALL were included in the study. Correlation of T-ALL subtypes with
      age, gender, and initial bone marrow and peripheral blood blast cells percentage
      was assessed using ANOVA. Results: Among the 50 T-ALL patients analyzed, 44 were
      male and six were female giving a male-to-female ratio of 7:1 (p = 0.007). The
      average age of patients was 19.2 years with no significant differences in the
      three disease subtypes. No significant association was seen between the
      peripheral or bone marrow blast cell percentage and the differentiation stages of
      the neoplastic clone of T-ALL. All female patients were found to express an
      immature T-ALL phenotype. Conclusions: This study reports the subtypes of T-ALL
      in Oman for the first time. It is hoped that this will lead to a better
      understanding of the disease outcomes.

PMID- 29467999
TI  - The Correlation of Cardiac and Hepatic Hemosiderosis as Measured by T2*MRI
      Technique with Ferritin Levels and Hemochromatosis Gene Mutations in Iranian
      Patients with Beta Thalassemia Major.
AB  - Objectives: Organ-specific hemosiderosis and iron overload complications are more
      serious and more frequent in some patients with beta thalassemia major (BTM)
      compared with others. We investigated whether coinheritance of HFE H63D or C282Y
      gene mutations in patients with BTM contributes to the phenotypic variation of
      iron overload complications and assessed the correlation of cardiac and hepatic
      hemosiderosis with plasma ferritin levels. Methods: We studied 60 patients with
      BTM with a mean age of 17.5+/-9.1 years from the Northwest of Iran. HFE gene
      mutations were analyzed using the polymerase chain reaction-restriction fragment
      length polymorphism method. Cardiac and hepatic hemosiderosis was assessed using
      T2*magnetic resonance imaging (MRI). Ferritin levels were measured using the
      enzyme immunoassay method. Results: Ferritin levels showed a strong inverse
      correlation with hepatic T2*MRI values (r = -0.631, p = 0.001) but a poor
      correlation with cardiac T2*MRI values (r = -0.297, p = 0.044). The correlation
      between cardiac T2*MRI values and hepatic T2*MRI values was poor and
      insignificant (r = 0.287, p = 0.058). Genotype and allele distribution of HFE
      H63D and C282Y mutation did not differ significantly between patients with and
      without hepatic or cardiac hemosiderosis (p > 0.050). However, carriers of HFE
      63D allele had significantly higher ferritin levels compared with non-carriers (1
      903+/-993 vs. 992+/-683, p < 0.001). Conclusions: Cardiac T2*MRI values showed a
      poor correlation with hepatic T2*MRI values and ferritin levels. Accurate
      assessment of cardiac iron overload in patients with BTM can only be done using
      the T2*MRI technique. Additionally, HFE H63D is a significant determinant factor
      for elevated ferritin levels in BTM patients.

PMID- 29468000
TI  - An Accurate Diagnostic Pathway Helps to Correctly Distinguish Between the
      Possible Causes of Acute Scrotum.
AB  - Objectives: We sought to identify a simplified approach for the rapid
      differential diagnosis of patients presenting with acute scrotum. Methods: A
      total of 440 patients referred to the emergency department of the University
      Hospital of Bern, Switzerland, with acute scrotum between 2003 and 2013 were
      retrospectively analyzed. Simple and multiple binary logistic regression analyses
      were used to evaluate clinical and laboratory parameters that may help to
      distinguish between genital/paragenital infection and acute testicular torsion.
      Results: Over half (58.4%; 257/440) of the patients were diagnosed with
      genital/paragenital infection, 11.8% (52/440) with chronic testicular pain, 9.5%
      (42/440) with acute testicular torsion, 4.3% (19/440) with a testicular cancer,
      and 2.5% (11/440) with symptomatic distal ureterolithiasis. In multivariate
      analysis, a positive Prehn's sign was predictive of testicular torsion, whereas
      fever, dysuria, high leucocyte counts in blood and/or urine, high blood C
      reactive protein, and burning pain were predictive of genital/paragenital
      infection. Color Doppler ultrasound did not help to distinguish between torsion
      and infection. Conclusions: An accurate diagnostic pathway helps to correctly
      distinguish between the possible causes of acute scrotum. However, none of the
      examinations performed could reliably distinguish between acute torsion and other
      causes of acute scrotum. Therefore, immediate surgical exploration of the testis
      is mandatory if torsion cannot be ruled out.

PMID- 29468001
TI  - Cerebral Venous Sinus Thrombosis in a Patient with Meningococcal Meningitis.
AB  - Meningococcal meningitis has a wide range of neurological complications. However,
      cerebral venous sinus thrombosis (CVST) following infection with Neisseria
      meningitidis is uncommon. We report a case of CVST in a 42-year-old male admitted
      with meningococcal meningitis. The patient was managed with antibiotics. Due to
      altered coagulation parameters observed in fulminant cases of meningococcemia,
      deployment of anticoagulation therapy, which would otherwise be the treatment of
      choice for CVST, is a dilemma.

PMID- 29468002
TI  - Idiopathic Non-traumatic Facial Nerve Palsy (Bell's Palsy) in Neonates; An
      Atypical Age and Management Dilemma.
AB  - Idiopathic (Bell's) palsy is the commonest cause of unilateral facial paralysis
      in children. Although being idiopathic by definition, possible infectious,
      inflammatory, and ischemic triggers have been suggested. Bell's palsy is thought
      to be responsible for up to three-fourths of cases of acute unilateral facial
      paralysis worldwide. The diagnosis has to be reached after other causes of acute
      peripheral palsy have been excluded. However, it is rarely described in neonates
      and young infants. Steroids may have some role in treatment, but antiviral
      therapies have doubtful evidence of benefit. Prognosis is good, though residual
      dysfunction is occasionally encountered. We report the case of a two-week-old
      neonate with no prior illnesses who presented with acute left facial palsy.
      Clinical findings and normal brain imaging were consistent with the diagnosis of
      Bell's palsy. The patient had a good response to oral steroids.

PMID- 29468003
TI  - Obstructed Hemivagina and Ipsilateral Renal Anomaly (OHVIRA) Syndrome.
AB  - Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome is a rare
      congenital abnormality of the female urogenital tract. We reported OHVIRA
      syndrome in a 15-year-old girl, who was referred to King Faisal Specialist
      Hospital and Research Centre, due to hematocolpos and an imperforate hymen. The
      patient was diagnosed as having an absent right kidney since childhood. She
      presented with progressive development of lower abdominal discomfort and an
      abdominopelvic mass. She had no history of urinary complaints. Here, we describe
      our findings from the abdominal ultrasound and magnetic resonance imaging.

PMID- 29468004
TI  - Fine-needle Aspiration Cytology of Abdominal Wall Endometriosis: ?A Meaningful
      Adjunct to Diagnosis.
AB  - Fine-needle aspiration cytology (FNAC) is a simple, non-invasive diagnostic
      modality which can be performed with ease on any superficially palpable lesion.
      Surgical scar endometriosis is a rare entity which presents as an abdominal lump
      in women of reproductive age. It is often a diagnostic pitfall for clinicians due
      to its nonspecific symptoms. It displays characteristic morphology, which needs
      to be identified and recognized by a cytopathologist for accurate diagnosis. FNAC
      can be used as a key diagnostic tool in cases of abdominal wall mass for
      appropriate patient management, thereby avoiding unnecessary diagnostic
      procedures. Here, we report the case of a 35-year-old woman who presented with an
      abdominal lump where FNAC played a vital role in the patient's management.

PMID- 29468005
TI  - Assessment of Trained Hand Hygiene Observers Using Parallel Observations.
AB  - Objectives: To validate hand hygiene (HH) observers following training and
      determine the concordance between the observers and the Kappa index. Methods:
      This study was conducted during June 2017. HH observers from 15 hospital units
      received eight-hours training including a two-hour workshop conducted by the
      infection control practitioner and hospital epidemiologist. After its completion,
      parallel observations were conducted by trained nurses from each respective unit
      for a maximum of 20 minutes per session at any time or day. Results: A total of
      789 parallel observations were performed. In observed HH actions, the percentage
      of agreement between trained and experienced observers was 75.4%, with a Kappa
      index of agreement of 0.61 (95% confidence interval (CI): 0.57-0.66). For the
      observed HH moments, the agreement among observers was 83.8% with a Kappa index
      of 0.71 (95% CI: 0.66-0.75). Conclusions: HH observers were validated after a
      dedicated training in correspondence with the recommendation to improve HH
      monitoring. Additional studies should focus on evaluating the sustainability of
      the agreement, the requirement of retraining, and other alternatives for
      observers' validation.

PMID- 29468006
TI  - Desquamative Lesion of the Nose and Lip.

PMID- 29468007
TI  - Which Exercise Performance is More Important for Cognition? Incremental or
      Protective Effects.

PMID- 29468008
TI  - Tactile Stimulation During Newborn Resuscitation: The Good, the Bad, and ?the
      Ugly.

PMID- 29468010
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1177/2041669517726797.].

PMID- 29468009
TI  - Is Red Heavier Than Yellow Even for Blind?
AB  - Across cultures and languages, people find similarities between the products of
      different senses in mysterious ways. By studying what is called cross-modal
      correspondences, cognitive psychologists discovered that lemons are fast rather
      than slow, boulders are sour, and red is heavier than yellow. Are these cross
      modal correspondences established via sensory perception or can they be learned
      merely through language? We contribute to this debate by demonstrating that early
      blind people who lack the perceptual experience of color also think that red is
      heavier than yellow but to a lesser extent than sighted do.

PMID- 29468011
TI  - Ligase IV inhibitor SCR7 enhances gene editing directed by CRISPR-Cas9 and ssODN
      in human cancer cells.
AB  - Background: Precise genome editing is essential for both basic and translational
      research. The recently developed CRISPR/Cas9 system can specifically cleave a
      designated site of target gene to create a DNA double-strand break, which
      triggers cellular DNA repair mechanism of either inaccurate non-homologous end
      joining, or site-specific homologous recombination. Unfortunately, homology
      directed repair (HDR) is challenging due to its very low efficiency. Herein, we
      focused on improving the efficiency of HDR using a combination of CRISPR/Cas9,
      eGFP, DNA ligase IV inhibitor SCR7, and single-stranded oligodeoxynucleotides
      (ssODN) in human cancer cells. Results: When Cas9, gRNA and eGFP were assembled
      into a co-expression vector, the disruption rate more than doubled following GFP
      positive cell sorting in transfected cells compared to those unsorted cells.
      Using ssODNs as templates, SCR7 treatment increased targeted insertion efficiency
      threefold in transfected cells compared to those without SCR7 treatment.
      Moreover, this combinatorial approach greatly improved the efficiency of HDR and
      targeted gene mutation correction at both the GFP-silent mutation and the beta
      catenin Ser45 deletion mutation cells. Conclusion: The data of this study
      suggests that a combination of co-expression vector, ssODN, and ligase IV
      inhibitor can markedly improve the CRISPR/Cas9-directed gene editing, which
      should have significant application in targeted gene editing and genetic disease
      therapy.

PMID- 29468012
TI  - The use of nutritional guidance within chiropractic patient management: a survey
      of 333 chiropractors from the ACORN practice-based research network.
AB  - Background: Food consumption and nutritional status affect an individual's health
      throughout their life-course and an unhealthy diet is a major risk factor for the
      current global burden of chronic disease. The promotion of health and good
      nutrition through healthy eating requires the active involvement of all health
      professionals including chiropractors. This paper reports findings from the first
      nationally representative examination of the use of nutritional guidance within
      chiropractic patient management in Australia. Methods: A sample of 1000
      practising chiropractors was randomly selected from the Australian Chiropractic
      Research Network (ACORN) practice-based research network database for a cross
      sectional study and 33% participated in the online survey in November 2016. The
      questionnaire, based on previous designs used in similar surveys and nutrition
      resources developed by the National Health and Medical Research Council, was
      pretested prior to the survey. Pearson's Chi square and bivariate logistic
      regression were undertaken to explore relationships with variables of interest.
      Results: The demographic details of the respondents are similar to those of the
      chiropractic workforce registered in Australia. Most chiropractors provided
      nutritional advice as part of their patient care and around a quarter provided
      specific dietary advice to their patients, including the use of nutrition
      supplements. Nutrition-related conditions most commonly encountered by the
      chiropractors were musculoskeletal, usually inflammatory in origin. Common
      nutritional assessment methods used included questioning patients to assess their
      nutritional and health status and physical appearance. Most of the participants
      provided nutritional resources to their patients in their clinics. However, the
      Australian Dietary Guidelines and the accompanying Australian Guide to Healthy
      Eating were not well utilised by the respondents. Australian chiropractors often
      referred patients with nutrition issues to qualified dietitians and other health
      professionals when deemed necessary. Conclusions: Australian chiropractors
      regularly provide nutritional advice and appear to acknowledge the importance of
      nutrition in their clinical practice especially for patients presenting with
      chronic disease. If chiropractors are to fulfil their potential in providing such
      wider public health and preventative health advice to patients, further research
      examining the utilisation of evidence-based nutrition resources within
      chiropractic patient management is recommended.

PMID- 29468013
TI  - Infrared heater system for warming tropical forest understory plants and soils.
AB  - The response of tropical forests to global warming is one of the largest
      uncertainties in predicting the future carbon balance of Earth. To determine the
      likely effects of elevated temperatures on tropical forest understory plants and
      soils, as well as other ecosystems, an infrared (IR) heater system was developed
      to provide in situ warming for the Tropical Responses to Altered Climate
      Experiment (TRACE) in the Luquillo Experimental Forest in Puerto Rico. Three
      replicate heated 4-m-diameter plots were warmed to maintain a 4 degrees C
      increase in understory vegetation compared to three unheated control plots, as
      sensed by IR thermometers. The equipment was larger than any used previously and
      was subjected to challenges different from those of many temperate ecosystem
      warming systems, including frequent power surges and outages, high humidity,
      heavy rains, hurricanes, saturated clayey soils, and steep slopes. The system was
      able to maintain the target 4.0 degrees C increase in hourly average vegetation
      temperatures to within +/- 0.1 degrees C. The vegetation was heterogeneous and on
      a 21 degrees  slope, which decreased uniformity of the warming treatment on the
      plots; yet, the green leaves were fairly uniformly warmed, and there was little
      difference among 0-10 cm depth soil temperatures at the plot centers, edges, and
      midway between. Soil temperatures at the 40-50 cm depth increased about 3 degrees
      C compared to the controls after a month of warming. As expected, the soil in the
      heated plots dried faster than that of the control plots, but the average soil
      moisture remained adequate for the plants. The TRACE heating system produced an
      adequately uniform warming precisely controlled down to at least 50-cm soil
      depth, thereby creating a treatment that allows for assessing mechanistic
      responses of tropical plants and soil to warming, with applicability to other
      ecosystems. No physical obstacles to scaling the approach to taller vegetation
      (i.e., trees) and larger plots were observed.

PMID- 29468014
TI  - A comparative analysis of Wolbachia-induced host reproductive phenotypes reveals
      transition rate heterogeneity.
AB  - The endosymbiotic bacterium Wolbachia infects a wide range of arthropods and
      their relatives. It is an intracellular parasite transmitted through the egg from
      mother to offspring. Wolbachia can spread and persist through various means of
      host reproductive manipulation. How these different mechanisms of host
      manipulation evolved in Wolbachia is unclear. Which host reproductive phenotype
      is most likely to be ancestral and whether evolutionary transitions between some
      host phenotypes are more common than others remain unanswered questions. Recent
      studies have revealed multiple cases where the same Wolbachia strain can induce
      different reproductive phenotypes in different hosts, raising the question to
      what degree the induced host phenotype should be regarded as a trait of
      Wolbachia. In this study, we constructed a phylogenetic tree of Wolbachia and
      analyzed the patterns of host phenotypes along that tree. We were able to detect
      a phylogenetic signal of host phenotypes on the Wolbachia tree, indicating that
      the induced host phenotype can be regarded as a Wolbachia trait. However, we
      found no clear support for the previously stated hypothesis that cytoplasmic
      incompatibility is ancestral to Wolbachia in arthropods. Our analysis provides
      evidence for heterogeneous transition rates between host phenotypes.

PMID- 29468015
TI  - You stay, but I Hop: Host shifting near and far co-dominated the evolution of
      Enchenopa treehoppers.
AB  - The importance and prevalence of phylogenetic tracking between hosts and
      dependent organisms caused by co-evolution and shifting between closely related
      host species have been debated for decades. Most studies of phylogenetic tracking
      among phytophagous insects and their host plants have been limited to insects
      feeding on a narrow range of host species. However, narrow host ranges can
      confound phylogenetic tracking (phylogenetic tracking hypothesis) with host
      shifting between hosts of intermediate relationship (intermediate hypothesis).
      Here, we investigated the evolutionary history of the Enchenopa binotata complex
      of treehoppers. Each species in this complex has high host fidelity, but the
      entire complex uses hosts across eight plant orders. The phylogenies of E.
      binotata were reconstructed to evaluate whether (1) tracking host phylogeny; or
      (2) shifting between intermediately related host plants better explains the
      evolutionary history of E. binotata. Our results suggest that E. binotata
      primarily shifted between both distant and intermediate host plants regardless of
      host phylogeny and less frequently tracked the phylogeny of their hosts. These
      findings indicate that phytophagous insects with high host fidelity, such as E.
      binotata, are capable of adaptation not only to closely related host plants but
      also to novel hosts, likely with diverse phenology and defense mechanisms.

PMID- 29468016
TI  - Are Hong Kong and Taiwan stepping-stones for invasive species to the mainland of
      China?
AB  - Understanding the origins and introduction pathways of invasive species is a
      fundamental issue for invasion biology, which is necessary for predicting and
      preventing future invasion. Once an invasive species is established in a new
      location, this location could serve as a stepping-stone for further invasions.
      However, such "stepping-stone" effect has not been widely investigated. Using the
      published literature and records, we compiled the first found locations of 127
      top invasive species in China. Our study showed that the most common landing
      spots of these invasive species were Hong Kong (22 species) and Taiwan (20
      species), which accounted for one-third of the invasive species in China. Our
      analysis revealed that the invasive species in mainland China were more likely to
      transport from Hong Kong than Macau, a neighboring region with a similar area and
      colonial history. Similarly, more invasive species were also first landed on
      Taiwan than Hainan, a nearby island sharing similar climate conditions. Together,
      our findings indicate that Hong Kong and Taiwan are the most important stepping
      stones for invasive species to the mainland of China and suggesting that the
      increasing trade exchange of China's coastal ports constitutes a potential risk
      for the spread of more invasive species. We suppose that they would be the future
      stepping-stones for invasive species to the mainland of China and these coastal
      ports regions where improved biosecurity is needed now.

PMID- 29468017
TI  - Useful surrogates of soil texture for plant ecologists from airborne gamma-ray
      detection.
AB  - Plant ecologists require spatial information on functional soil properties but
      are often faced with soil classifications that are not directly interpretable or
      useful for statistical models. Sand and clay content are important soil
      properties because they indicate soil water-holding capacity and nutrient
      content, yet these data are not available for much of the landscape. Remotely
      sensed soil radiometric data offer promise for developing statistical models of
      functional soil properties applicable over large areas. Here, we build models
      linking radiometric data for an area of 40,000 km2 with soil physicochemical data
      collected over a period of 30 years and demonstrate a strong relationship between
      gamma radiometric potassium (40K), thorium (232Th), and soil sand and clay
      content. Our models showed predictive performance of 43% with internal cross
      validation (to held-out data) and ~30% for external validation to an independent
      test dataset. This work contributes to broader availability and uptake of remote
      sensing products for explaining patterns in plant distribution and performance
      across landscapes.

PMID- 29468018
TI  - Does governance play a role in the distribution of invasive alien species?
AB  - Invasive alien species (IAS) constitute a major threat to global biological
      diversity. In order to control their spread, a detailed understanding of the
      factors influencing their distribution is essential. Although international trade
      is regarded as a major force structuring spatial patterns of IAS, the role of
      other social factors remains unclear. Despite studies highlighting the importance
      of strong governance in slowing drivers of biodiversity loss such as logging,
      deforestation, and agricultural intensification, no study has yet analyzed its
      contribution to the issue of IAS. Using estimates of governance quality and
      comprehensive spatiotemporal IAS data, we performed multiple linear regressions
      to investigate the effect of governance quality upon the distribution of species
      listed under "100 of the worst" IAS in 38 Eurasian countries as defined by DASIE.
      Our model suggested that for countries with higher GDP, stronger governance was
      associated with a greater number of the worst IAS; in contrast, for the lowest
      GDP countries under analysis, stronger governance was associated with fewer of
      these IAS. We elucidate how the quality of governance within a country has
      implications for trade, tourism, transport, legislation, and economic
      development, all of which influence the spread of IAS. While our findings support
      the common assumption that strengthening governance benefits conservation
      interventions in countries of smaller economy, we find that this effect is not
      universal. Stronger governance alone cannot adequately address the problem of
      IAS, and targeted action is required in relatively high-GDP countries in order to
      stem the influx of IAS associated with high volumes of trade.

PMID- 29468019
TI  - Disentangling population strategies of two cladocerans adapted to different
      ultraviolet regimes.
AB  - Zooplankton have evolved several mechanisms to deal with environmental threats,
      such as ultraviolet radiation (UVR), and in order to identify strategies inherent
      to organisms exposed to different UVR environments, we here examine life-history
      traits of two lineages of Daphnia pulex. The lineages differed in the UVR dose
      they had received at their place of origin from extremely high UVR stress at high
      altitude Bolivian lakes to low UVR stress near the sea level in temperate Sweden.
      Nine life-history variables of each lineage were analyzed in laboratory
      experiments in the presence and the absence of sub-lethal doses of UVR (UV-A
      band), and we identified trade-offs among variables through structural equation
      modeling (SEM). The UVR treatment was detrimental to almost all life-history
      variables of both lineages; however, the Daphnia historically exposed to higher
      doses of UVR (HighUV) showed a higher overall fecundity than those historically
      exposed to lower doses of UVR (LowUV). The total offspring and ephippia
      production, as well as the number of clutches and number of offspring at first
      reproduction, was directly affected by UVR in both lineages. Main differences
      between lineages involved indirect effects that affected offspring production as
      the age at first reproduction. We here show that organisms within the same
      species have developed different strategies as responses to UVR, although no
      increased physiological tolerance or plasticity was shown by the HighUV lineage.
      In addition to known tolerance strategies to UVR, including avoidance,
      prevention, or repairing of damages, we here propose a population strategy that
      includes early reproduction and high fertility, which we show compensated for the
      fitness loss imposed by UVR stress.

PMID- 29468020
TI  - Life-history traits and physiological limits of the alpine fly Drosophila
      nigrosparsa (Diptera: Drosophilidae): A comparative study.
AB  - Interspecific variation in life-history traits and physiological limits can be
      linked to the environmental conditions species experience, including climatic
      conditions. As alpine environments are particularly vulnerable under climate
      change, we focus on the montane-alpine fly Drosophila nigrosparsa. Here, we
      characterized some of its life-history traits and physiological limits and
      compared these with those of other drosophilids, namely Drosophila hydei,
      Drosophila melanogaster, and Drosophila obscura. We assayed oviposition rate,
      longevity, productivity, development time, larval competitiveness, starvation
      resistance, and heat and cold tolerance. Compared with the other species assayed,
      D. nigrosparsa is less fecund, relatively long-living, starvation susceptible,
      cold adapted, and surprisingly well heat adapted. These life-history
      characteristics provide insights into invertebrate adaptations to alpine
      conditions which may evolve under ongoing climate change.

PMID- 29468021
TI  - Aberrant clones: Birth order generates life history diversity in Greater
      Duckweed, Spirodela polyrhiza.
AB  - Environmental unpredictability is known to result in the evolution of bet-hedging
      traits. Variable dormancy enhances survival through harsh conditions, and is
      widely cited as a diversification bet-hedging trait. The floating aquatic plant,
      Spirodela polyrhiza (Greater Duckweed), provides an opportunity to study
      diversification because although partially reliable seasonal cues exist, its
      growing season is subject to an unpredictable and literally "hard" termination
      when the surface water freezes, and overwinter survival depends on a switch from
      production of normal daughter fronds to production of dense, sinking "turions"
      prior to freeze-over. The problem for S. polyrhiza is that diversified dormancy
      behavior must be generated among clonally produced, genetically identical
      offspring. Variation in phenology has been observed in the field, but its sources
      are unknown. Here, we investigate sources of phenological variation in turion
      production, and test the hypothesis that diversification in turion phenology is
      generated within genetic lineages through effects of parental birth order. As
      expected, phenotypic plasticity to temperature is expressed along a thermal
      gradient; more interestingly, parental birth order was found to have a
      significant and strong effect on turion phenology: Turions are produced earlier
      by late birth-order parents. These results hold regardless of whether turion
      phenology is measured as first turion birth order, time to first turion, or
      turion frequency. This study addresses a question of current interest on
      potential mechanisms generating diversification, and suggests that consistent
      phenotypic differences across birth orders generate life history variation.

PMID- 29468022
TI  - How to tackle chemical communication? Relative proportions versus
      semiquantitative determination of compounds in lizard chemical secretions.
AB  - Knowledge about chemical communication in some vertebrates is still relatively
      limited. Squamates are a glaring example of this, even when recent evidences
      indicate that scents are involved in social and sexual interactions. In lizards,
      where our understanding of chemical communication has considerably progressed in
      the last few years, many questions about chemical interactions remain unanswered.
      A potential reason for this is the inherent complexity and technical limitations
      that some methodologies embody when analyzing the compounds used to convey
      information. We provide here a straightforward procedure to analyze lizard
      chemical secretions based on gas chromatography coupled to mass spectrometry that
      uses an internal standard for the semiquantification of compounds. We compare the
      results of this method with those obtained by the traditional procedure of
      calculating relative proportions of compounds. For such purpose, we designed two
      experiments to investigate if these procedures allowed revealing changes in
      chemical secretions 1) when lizards received previously a vitamin dietary
      supplementation or 2) when the chemical secretions were exposed to high
      temperatures. Our results show that the procedure based on relative proportions
      is useful to describe the overall chemical profile, or changes in it, at
      population or species levels. On the other hand, the use of the procedure based
      on semiquantitative determination can be applied when the target of study is the
      variation in one or more particular compounds of the sample, as it has proved
      more accurate detecting quantitative variations in the secretions. This method
      would reveal new aspects produced by, for example, the effects of different
      physiological and climatic factors that the traditional method does not show.

PMID- 29468023
TI  - Community-level plant-soil feedbacks explain landscape distribution of native and
      non-native plants.
AB  - Plant-soil feedbacks (PSFs) have gained attention for their potential role in
      explaining plant growth and invasion. While promising, most PSF research has
      measured plant monoculture growth on different soils in short-term, greenhouse
      experiments. Here, five soil types were conditioned by growing one native
      species, three non-native species, or a mixed plant community in different plots
      in a common-garden experiment. After 4 years, plants were removed and one native
      and one non-native plant community were planted into replicate plots of each soil
      type. After three additional years, the percentage cover of each of the three
      target species in each community was measured. These data were used to
      parameterize a plant community growth model. Model predictions were compared to
      native and non-native abundance on the landscape. Native community cover was
      lowest on soil conditioned by the dominant non-native, Centaurea diffusa, and non
      native community cover was lowest on soil cultivated by the dominant native,
      Pseudoroegneria spicata. Consistent with plant growth on the landscape, the plant
      growth model predicted that the positive PSFs observed in the common-garden
      experiment would result in two distinct communities on the landscape: a native
      plant community on native soils and a non-native plant community on non-native
      soils. In contrast, when PSF effects were removed, the model predicted that non
      native plants would dominate all soils, which was not consistent with plant
      growth on the landscape. Results provide an example where PSF effects were large
      enough to change the rank-order abundance of native and non-native plant
      communities and to explain plant distributions on the landscape. The positive
      PSFs that contributed to this effect reflected the ability of the two dominant
      plant species to suppress each other's growth. Results suggest that plant
      dominance, at least in this system, reflects the ability of a species to suppress
      the growth of dominant competitors through soil-mediated effects.

PMID- 29468024
TI  - Age, state, environment, and season dependence of senescence in body mass.
AB  - Senescence is a highly variable process that comprises both age-dependent and
      state-dependent components and can be greatly affected by environmental
      conditions. However, few studies have quantified the magnitude of age-dependent
      and state-dependent senescence in key life-history traits across individuals
      inhabiting different spatially structured and seasonal environments. We used
      longitudinal data from wild female yellow-bellied marmots (Marmota flaviventer),
      living in two adjacent environments that differ in elevation and associated
      phenology, to quantify how age and individual state, measured as "time to death,"
      affect body mass senescence in different environments. Further, we quantified how
      patterns of senescence differed between two biologically distinct seasons,
      spring, and late summer. Body mass senescence had an age-dependent component,
      expressed as a decrease in mass in old age. Overall, estimated age-dependent
      senescence was greater in females living in the more favorable lower elevation
      environment, than in the harsher higher elevation environment, and greater in
      late summer than in spring. Body mass senescence also had a state-dependent
      component, captured by effects of time to death, but only in the more favorable
      lower elevation environment. In spring, body mass gradually decreased from 2
      years before death, whereas in late summer, state-dependent effects were
      expressed as a terminal decrease in body mass in the last year of life. Contrary
      to expectations, we found that senescence was more likely to be observed under
      more favorable environmental conditions, rather than under harsher conditions. By
      further demonstrating that senescence patterns differ among seasons, our results
      imply that within-year temporal environmental variation must be considered
      alongside spatial environmental variation in order to characterize and understand
      the pattern and magnitude of senescence in wild populations.

PMID- 29468025
TI  - Range contraction and increasing isolation of a polar bear subpopulation in an
      era of sea-ice loss.
AB  - Climate change is expected to result in range shifts and habitat fragmentation
      for many species. In the Arctic, loss of sea ice will reduce barriers to
      dispersal or eliminate movement corridors, resulting in increased connectivity or
      geographic isolation with sweeping implications for conservation. We used
      satellite telemetry, data from individually marked animals (research and
      harvest), and microsatellite genetic data to examine changes in geographic range,
      emigration, and interpopulation connectivity of the Baffin Bay (BB) polar bear
      (Ursus maritimus) subpopulation over a 25-year period of sea-ice loss. Satellite
      telemetry collected from n = 43 (1991-1995) and 38 (2009-2015) adult females
      revealed a significant contraction in subpopulation range size (95% bivariate
      normal kernel range) in most months and seasons, with the most marked reduction
      being a 70% decline in summer from 716,000 km2 (SE 58,000) to 211,000 km2 (SE
      23,000) (p < .001). Between the 1990s and 2000s, there was a significant shift
      northward during the on-ice seasons (2.6 degrees  shift in winter median
      latitude, 1.1 degrees  shift in spring median latitude) and a significant range
      contraction in the ice-free summers. Bears in the 2000s were less likely to leave
      BB, with significant reductions in the numbers of bears moving into Davis Strait
      (DS) in winter and Lancaster Sound (LS) in summer. Harvest recoveries suggested
      both short and long-term fidelity to BB remained high over both periods (83-99%
      of marked bears remained in BB). Genetic analyses using eight polymorphic
      microsatellites confirmed a previously documented differentiation between BB, DS,
      and LS; yet weakly differentiated BB from Kane Basin (KB) for the first time. Our
      results provide the first multiple lines of evidence for an increasingly
      geographically and functionally isolated subpopulation of polar bears in the
      context of long-term sea-ice loss. This may be indicative of future patterns for
      other polar bear subpopulations under climate change.

PMID- 29468026
TI  - The effect of isolation, fragmentation, and population bottlenecks on song
      structure of a Hawaiian honeycreeper.
AB  - Little is known about how important social behaviors such as song vary within and
      among populations for any of the endemic Hawaiian honeycreepers. Habitat loss and
      non-native diseases (e.g., avian malaria) have resulted in isolation and
      fragmentation of Hawaiian honeycreepers within primarily high elevation forests.
      In this study, we examined how isolation of Hawai'i 'amakihi (Chlorodrepanis
      virens) populations within a fragmented landscape influences acoustic variability
      in song. In the last decade, small, isolated populations of disease tolerant
      'amakihi have been found within low elevation forests, allowing us to record
      'amakihi songs across a large elevational gradient (10-1800 m) that parallels
      disease susceptibility on Hawai'i island. To understand underlying differences
      among populations, we examined the role of geographic distance, elevation, and
      habitat structure on acoustic characteristics of 'amakihi songs. We found that
      the acoustic characteristics of 'amakihi songs and song-type repertoires varied
      most strongly across an elevational gradient. Differences in 'amakihi song types
      were primarily driven by less complex songs (e.g., fewer frequency changes,
      shorter songs) of individuals recorded at low elevation sites compared to mid and
      high elevation populations. The reduced complexity of 'amakihi songs at low
      elevation sites is most likely shaped by the effects of habitat fragmentation and
      a disease-driven population bottleneck associated with avian malaria, and
      maintained through isolation, localized song learning and sharing, and cultural
      drift. These results highlight how a non-native disease through its influence on
      population demographics may have also indirectly played a role in shaping the
      acoustic characteristics of a species.

PMID- 29468027
TI  - Age-dependent, negative heterozygosity-fitness correlations and local effects in
      an endangered Caribbean reptile, Iguana delicatissima.
AB  - Inbreeding depression can have alarming impacts on threatened species with small
      population sizes. Assessing inbreeding has therefore become an important focus of
      conservation research. In this study, heterozygosity-fitness correlations (HFCs)
      were measured by genotyping 7 loci in 83 adult and 184 hatchling Lesser Antillean
      Iguanas, Iguana delicatissima, at a communal nesting site in Dominica to assess
      the role of inbreeding depression on hatchling fitness and recruitment to the
      adult population in this endangered species. We found insignificant correlations
      between multilocus heterozygosity and multiple fitness proxies in hatchlings and
      adults. Further, multilocus heterozygosity did not differ significantly between
      hatchlings and adults, which suggests that the survivorship of homozygous
      hatchlings does not differ markedly from that of their heterozygous counterparts.
      However, genotypes at two individual loci were correlated with hatching date, a
      finding consistent with the linkage between specific marker loci and segregating
      deleterious recessive alleles. These results provide only modest evidence that
      inbreeding depression influences the population dynamics of I. delicatissima on
      Dominica.

PMID- 29468028
TI  - Paleoecological evidence for decadal increase in phytoplankton biomass off
      northwestern Australia in response to climate change.
AB  - Ocean warming can modify the phytoplankton biomass on decadal scales. Significant
      increases in sea surface temperature (SST) and rainfall in the northwest of
      Australia over recent decades are attributed to climate change. Here, we used
      four biomarker proxies (TEX86 index, long-chain n-alkanes, brassicasterol, and
      dinosterol) to reconstruct approximately 60-year variations of SST, terrestrial
      input, and diatom and dinoflagellate biomass in the coastal waters of the remote
      Kimberley region. The results showed that the most significant increases in SST
      and terrestrial input occurred since 1997, accompanied by an abrupt increase in
      diatom and dinoflagellate biomasses. Compared with the results before 1997, the
      average TEX86H temperature during 1997-2011 increased approximately 1 degrees C,
      rainfall increased 248.2 mm, brassicasterol and dinosterol contents increased 8.5
      and 1.7 times. Principal component analysis indicated that the warming SST played
      a more important role in the phytoplankton increase than increased rainfall and
      river discharge.

PMID- 29468029
TI  - Patterns of activity and body temperature of Aldabra giant tortoises in relation
      to environmental temperature.
AB  - We studied the temperature relations of wild and zoo Aldabra giant tortoises
      (Aldabrachelys gigantea) focusing on (1) the relationship between environmental
      temperature and tortoise activity patterns (n = 8 wild individuals) and (2) on
      tortoise body temperature fluctuations, including how their core and external
      body temperatures vary in relation to different environmental temperature ranges
      (seasons; n = 4 wild and n = 5 zoo individuals). In addition, we surveyed the
      literature to review the effect of body mass on core body temperature range in
      relation to environmental temperature in the Testudinidae. Diurnal activity of
      tortoises was bimodally distributed and influenced by environmental temperature
      and season. The mean air temperature at which activity is maximized was 27.9
      degrees C, with a range of 25.8-31.7 degrees C. Furthermore, air temperature
      explained changes in the core body temperature better than did mass, and only
      during the coldest trial, did tortoises with higher mass show more stable
      temperatures. Our results, together with the overall Testudinidae overview,
      suggest that, once variation in environmental temperature has been taken into
      account, there is little effect of mass on the temperature stability of
      tortoises. Moreover, the presence of thermal inertia in an individual tortoise
      depends on the environmental temperatures, and we found no evidence for inertial
      homeothermy. Finally, patterns of core and external body temperatures in
      comparison with environmental temperatures suggest that Aldabra giant tortoises
      act as mixed conformer-regulators. Our study provides a baseline to manage the
      thermal environment of wild and rewilded populations of an important island
      ecosystem engineer species in an era of climate change.

PMID- 29468030
TI  - Introgression of exotic Cervus (nippon and canadensis) into red deer (Cervus
      elaphus) populations in Scotland and the English Lake District.
AB  - Since the mid-19th century, multiple introductions of Japanese sika deer (Cervus
      nippon nippon) and North American wapiti (C. canadensis) have taken place in the
      British Isles. While wapiti have generally been unsuccessful, sika have been very
      successful, especially in Scotland where they now overlap at least 40% of the
      range of native red deer (C. elaphus). Hybridization between these two species
      and red deer has been demonstrated in captivity and in the wild. Using a panel of
      22 microsatellite loci that are highly diagnostic between red deer and sika, and
      moderately diagnostic between red deer and wapiti, we investigated the extent of
      introgression between these species in 2,943 deer sampled from around Scotland
      and from the English Lake District using the Bayesian clustering software
      STRUCTURE. We also used a diagnostic mitochondrial marker for red deer and sika.
      Our survey extends previous studies indicating little introgression of wapiti
      nuclear alleles into red deer, in particular in Northern Scotland, Kintyre, and
      the Lake District. We found a new area of extensive sika introgression in South
      Kintyre. In the North Highlands, we show for the first time geographically
      scattered evidence of past hybridization followed by extensive backcrossing,
      including one red-like individual with sika introgression, two sika-like
      individuals with red deer introgression, and six individuals that were apparently
      pure sika at the nuclear markers assessed but which carried red deer
      mitochondria. However, there has not been a collapse of assortative mating in
      this region. Similarly, in the English Lake District red deer, we found only
      traces of past sika introgression. No sika alleles were detected in the Central
      Highlands or the Hebridean red deer refugia. We make suggestions for management
      to prevent further spread of sika alleles into red deer and vice versa.

PMID- 29468031
TI  - Reproduction of parasitic mites Varroa destructor in original and new honeybee
      hosts.
AB  - The ectoparasitic mite, Varroa destructor, shifted host from the eastern
      honeybee, Apis cerana, to the western honeybee, Apis mellifera. Whereas the
      original host survives infestations by this parasite, they are lethal to colonies
      of its new host. Here, we investigated a population of A. cerana naturally
      infested by the V. destructor Korea haplotype that gave rise to the globally
      invasive mite lineage. Our aim was to better characterize traits that allow for
      the survival of the original host to infestations by this particular mite
      haplotype. A known major trait of resistance is the lack of mite reproduction on
      worker brood in A. cerana. We show that this trait is neither due to a lack of
      host attractiveness nor of reproduction initiation by the parasite. However,
      successful mite reproduction was prevented by abnormal host development. Adult A.
      cerana workers recognized this state and removed hosts and parasites, which
      greatly affected the fitness of the parasite. These results confirm and complete
      previous observations of brood susceptibility to infestation in other honeybee
      host populations, provide new insights into the coevolution between hosts and
      parasites in this system, and may contribute to mitigating the large-scale colony
      losses of A. mellifera due to V. destructor.

PMID- 29468032
TI  - Female mate choice of male signals is unlikely to promote ecological adaptation
      in Enchenopa treehoppers (Hemiptera: Membracidae).
AB  - A key question in speciation research is how ecological and sexual divergence
      arise and interact. We tested the hypothesis that mate choice causes local
      adaptation and ecological divergence using the rationale that the
      performance~signal trait relationship should parallel the attractiveness~signal
      trait relationship. We used female fecundity as a measure of ecological
      performance. We used a species in the Enchenopa binotata treehopper complex,
      wherein speciation involves adaptation to novel environments and divergence in
      sexual communication. We used a full-sibling, split-family rearing design to
      estimate genetic correlations (rG) between fecundity and signal traits, and
      compared those relationships against population-level mate preferences for the
      signal traits. Animal model estimates for rG between female fecundity and male
      signal traits overlapped zero-rejecting the hypothesis-but could reflect sample
      size limitations. The magnitude of rG correlated with the strength of the mate
      preferences for the corresponding signal traits, especially for signal frequency,
      which has the strongest mate preference and the most divergence in the complex.
      However, signal frequencies favored by the population-level mate preference are
      not associated with high fecundity. Therefore, mate preferences do not appear to
      have been selected to favor high-performance genotypes. Our findings suggest that
      ecological and sexual divergence may arise separately, but reinforce each other,
      during speciation.

PMID- 29468033
TI  - Recolonizing gray wolves increase parasite infection risk in their prey.
AB  - The recent recolonization of Central Europe by the European gray wolf (Canis
      lupus) provides an opportunity to study the dynamics of parasite transmission for
      cases when a definitive host returns after a phase of local extinction. We
      investigated whether a newly established wolf population increased the prevalence
      of those parasites in ungulate intermediate hosts representing wolf prey, whether
      some parasite species are particularly well adapted to wolves, and the potential
      basis for such adaptations. We recorded Sarcocystis species richness in wolves
      and Sarcocystis prevalence in ungulates harvested in study sites with and without
      permanent wolf presence in Germany using microscopy and DNA metabarcoding.
      Sarcocystis prevalence in red deer (Cervus elaphus) was significantly higher in
      wolf areas (79.7%) than in control areas (26.3%) but not in roe deer (Capreolus
      capreolus) (97.2% vs. 90.4%) or wild boar (Sus scrofa) (82.8% vs. 64.9%). Of 11
      Sarcocystis species, Sarcocystis taeniata and Sarcocystis grueneri occurred more
      often in wolves than expected from the Sarcocystis infection patterns of ungulate
      prey. Both Sarcocystis species showed a higher increase in prevalence in
      ungulates in wolf areas than other Sarcocystis species, suggesting that they are
      particularly well adapted to wolves, and are examples of "wolf specialists".
      Sarcocystis species richness in wolves was significantly higher in pups than in
      adults. "Wolf specialists" persisted during wolf maturation. The results of this
      study demonstrate that (1) predator-prey interactions influence parasite
      prevalence, if both predator and prey are part of the parasite life cycle, (2)
      mesopredators do not necessarily replace the apex predator in parasite
      transmission dynamics for particular parasites of which the apex predator is the
      definitive host, even if meso- and apex predators were from the same taxonomic
      family (here: Canidae, e.g., red foxes Vulpes vulpes), and (3) age-dependent
      immune maturation contributes to the control of protozoan infection in wolves.

PMID- 29468034
TI  - Frequency and intensity of facilitation reveal opposing patterns along a stress
      gradient.
AB  - Disentangling the different processes structuring ecological communities is a
      long-standing challenge. In species-rich ecosystems, most emphasis has so far
      been given to environmental filtering and competition processes, while
      facilitative interactions between species remain insufficiently studied. Here, we
      propose an analysis framework that not only allows for identifying pairs of
      facilitating and facilitated species, but also estimates the strength of
      facilitation and its variation along environmental gradients. Our framework
      combines the analysis of both co-occurrence and co-abundance patterns using a
      moving window approach along environmental gradients to control for potentially
      confounding effects of environmental filtering in the co-abundance analysis. We
      first validate our new approach against community assembly simulations, and
      exemplify its potential on a large 1,134 plant community plots dataset. Our
      results generally show that facilitation intensity was strongest under cold
      stress, whereas the proportion of facilitating and facilitated species was higher
      under drought stress. Moreover, the functional distance between individual
      facilitated species and their facilitating species significantly changed along
      the temperature-moisture gradient, and seemed to influence facilitation
      intensity, although no general positive or general negative trend was discernible
      among species. The main advantages of our robust framework are as follows: It
      enables detecting facilitating and facilitated species in species-rich systems,
      and it allows identifying the directionality and intensity of facilitation in
      species pairs as well as its variation across long environmental gradients. It
      thus opens numerous opportunities for incorporating functional (and phylogenetic)
      information in the analysis of facilitation patterns. Our case study indicated
      high complexity in facilitative interactions across the stress gradient and
      revealed new evidence that facilitation, similarly to competition, can operate
      between functionally similar and dissimilar species. Extending the analyses to
      other taxa and ecosystems will foster our understanding how complex interspecific
      interactions promote biodiversity.

PMID- 29468035
TI  - Cryptic species and parallel genetic structuring in Lethrinid fish: Implications
      for conservation and management in the southwest Indian Ocean.
AB  - Analysis of genetic variation can provide insights into ecological and
      evolutionary diversification which, for commercially harvested species, can also
      be relevant to the implementation of spatial management strategies and
      sustainability. In comparison with other marine biodiversity hot spots, there has
      been less genetic research on the fauna of the southwest Indian Ocean (SWIO).
      This is epitomized by the lack of information for lethrinid fish, which support
      socioeconomically important fisheries in the region. This study combines
      comparative phylogeographic and population genetic analyses with ecological niche
      modeling to investigate historical and contemporary population dynamics of two
      species of emperor fish (Lethrinus mahsena and Lethrinus harak) across the SWIO.
      Both species shared similarly shallow phylogeographic patterns and modeled
      historical (LGM) habitat occupancies. For both species, allele frequency and
      kinship analyses of microsatellite variation revealed highly significant
      structure with no clear geographical pattern and nonrandom genetic relatedness
      among individuals within samples. The genetic patterns for both species indicate
      recurrent processes within the region that prevent genetic mixing, at least on
      timescales of interest to fishery managers, and the potential roles of
      recruitment variability and population isolation are discussed in light of
      biological and environmental information. This consistency in both historical and
      recurrent population processes indicates that the use of model species may be
      valuable in management initiatives with finite resources to predict population
      structure, at least in cases wherein biogeographic and ecological differences
      between taxa are minimized. Paradoxically, mtDNA sequencing and microsatellite
      analysis of samples from the Seychelles revealed a potential cryptic species
      occurring in sympatry with, and seemingly morphologically identical to, L.
      mahsena. BLAST results point to the likely misidentification of species and
      incongruence between voucher specimens, DNA barcodes, and taxonomy within the
      group, which highlights the utility and necessity of genetic approaches to
      characterize baseline biodiversity in the region before such model-based methods
      are employed.

PMID- 29468036
TI  - Wrong, but useful: regional species distribution models may not be improved by
      range-wide data under biased sampling.
AB  - Species distribution modeling (SDM) is an essential method in ecology and
      conservation. SDMs are often calibrated within one country's borders, typically
      along a limited environmental gradient with biased and incomplete data, making
      the quality of these models questionable. In this study, we evaluated how
      adequate are national presence-only data for calibrating regional SDMs. We
      trained SDMs for Egyptian bat species at two different scales: only within Egypt
      and at a species-specific global extent. We used two modeling algorithms: Maxent
      and elastic net, both under the point-process modeling framework. For each
      modeling algorithm, we measured the congruence of the predictions of global and
      regional models for Egypt, assuming that the lower the congruence, the lower the
      appropriateness of the Egyptian dataset to describe the species' niche. We
      inspected the effect of incorporating predictions from global models as
      additional predictor ("prior") to regional models, and quantified the improvement
      in terms of AUC and the congruence between regional models run with and without
      priors. Moreover, we analyzed predictive performance improvements after
      correction for sampling bias at both scales. On average, predictions from global
      and regional models in Egypt only weakly concur. Collectively, the use of priors
      did not lead to much improvement: similar AUC and high congruence between
      regional models calibrated with and without priors. Correction for sampling bias
      led to higher model performance, whatever prior used, making the use of priors
      less pronounced. Under biased and incomplete sampling, the use of global bats
      data did not improve regional model performance. Without enough bias-free
      regional data, we cannot objectively identify the actual improvement of regional
      models after incorporating information from the global niche. However, we still
      believe in great potential for global model predictions to guide future surveys
      and improve regional sampling in data-poor regions.

PMID- 29468037
TI  - Single-nucleotide polymorphism discovery and panel characterization in the
      African forest elephant.
AB  - The continuing decline in forest elephant (Loxodonta cyclotis) numbers due to
      poaching and habitat reduction is driving the search for new tools to inform
      management and conservation. For dense rainforest species, basic ecological data
      on populations and threats can be challenging and expensive to collect, impeding
      conservation action in the field. As such, genetic monitoring is being
      increasingly implemented to complement or replace more burdensome field
      techniques. Single-nucleotide polymorphisms (SNPs) are particularly cost
      effective and informative markers that can be used for a range of practical
      applications, including population census, assessment of human impact on social
      and genetic structure, and investigation of the illegal wildlife trade. SNP
      resources for elephants are scarce, but next-generation sequencing provides the
      opportunity for rapid, inexpensive generation of SNP markers in nonmodel species.
      Here, we sourced forest elephant DNA from 23 samples collected from 10 locations
      within Gabon, Central Africa, and applied double-digest restriction-site
      associated DNA (ddRAD) sequencing to discover 31,851 tags containing SNPs that
      were reduced to a set of 1,365 high-quality candidate SNP markers. A subset of
      115 candidate SNPs was then selected for assay design and validation using 56
      additional samples. Genotyping resulted in a high conversion rate (93%) and a low
      per allele error rate (0.07%). This study provides the first panel of 107
      validated SNP markers for forest elephants. This resource presents great
      potential for new genetic tools to produce reliable data and underpin a step
      change in conservation policies for this elusive species.

PMID- 29468038
TI  - Functional trade-offs and the phylogenetic dispersion of seed traits in a
      biodiversity hotspot of the Mountains of Southwest China.
AB  - The diversity of traits associated with plant regeneration is often shaped by
      functional trade-offs where plants typically do not excel at every function
      because resources allocated to one function cannot be allocated to another. By
      analyzing correlations among seed traits, empirical studies have shown that there
      is a trade-off between seedling development and the occupation of new habitats,
      although only a small range of taxa have been tested; whether such trade-off
      exists in a biodiverse and complex landscape remains unclear. Here, we amassed
      seed trait data of 1,119 species from a biodiversity hotspot of the Mountains of
      Southwest China and analyzed the relationship between seed mass and the number of
      seeds and between seed mass and time to germination. Our results showed that seed
      mass was negatively correlated with seed number but positively correlated with
      time to germination. The same trend was found regardless of variation in life
      form and phylogenetic conservatism. Furthermore, the relation between seed mass
      and other seed traits was randomly dispersed across the phylogeny at both the
      order and family levels. Collectively, results suggest that there is a functional
      trade-off between seedling development and new habitat occupation for seed plants
      in this region. Larger seeds tend to produce fewer seedlings but with greater
      fitness compared to those produced by smaller seeds, whereas smaller seeds tend
      to have a larger number of seeds that germinate faster compared to large-seeded
      species. Apart from genetic constraints, species that produce large seeds will
      succeed in sites where resource availability is low, whereas species with high
      colonization ability (those that produce a high number of seeds per fruit) will
      succeed in new niches. This study provides a mechanistic explanation for the
      relatively high levels of plant diversity currently found in a heterogeneous
      region of the Mountains of Southwest China.

PMID- 29468039
TI  - Differences among six woody perennials native to Northern Europe in their level
      of genetic differentiation and adaptive potential at fine local scale.
AB  - The ability of perennial species to adapt their phenology to present and future
      temperature conditions is important for their ability to retain high fitness
      compared to other competing plant species, pests, and pathogens. Many
      transplanting studies with forest tree species have previously reported
      substantial genetic differentiation among populations within their native range.
      However, the question of "how local is local" is still highly debated in
      conservation biology because studies on genetic patterns of variation within and
      among populations at the local scale are limited and scattered. In this study, we
      compare the level of genetic differentiation among populations of six different
      perennial plant species based on their variation in spring flushing. We assess
      the level of additive genetic variation present within the local population. For
      all six species, we find significant differentiation among populations from sites
      with mean annual temperature ranging between 7.4 degrees C and 8.4 degrees C. The
      observed variation can only be partly explained by the climate at the site of
      origin. Most clear relationship between early flushing and higher average spring
      temperature is observed for the three wind-pollinated species in the study, while
      the relations are much less clear for the three insect-pollinated species. This
      supports that pollination system can influence the balance between genetic drift
      and natural selection and thereby influence the level of local adaptation in long
      lived species. On the positive side, we find that the native populations of woody
      plant species have maintained high levels of additive genetic variation in spring
      phenology, although this also differs substantially among the six studied
      species.

PMID- 29468040
TI  - Dominance of Endozoicomonas bacteria throughout coral bleaching and mortality
      suggests structural inflexibility of the Pocillopora verrucosa microbiome.
AB  - The importance of Symbiodinium algal endosymbionts and a diverse suite of
      bacteria for coral holobiont health and functioning are widely acknowledged. Yet,
      we know surprisingly little about microbial community dynamics and the stability
      of host-microbe associations under adverse environmental conditions. To gain
      insight into the stability of coral host-microbe associations and holobiont
      structure, we assessed changes in the community structure of Symbiodinium and
      bacteria associated with the coral Pocillopora verrucosa under excess organic
      nutrient conditions. Pocillopora-associated microbial communities were monitored
      over 14 days in two independent experiments. We assessed the effect of excess
      dissolved organic nitrogen (DON) and excess dissolved organic carbon (DOC).
      Exposure to excess nutrients rapidly affected coral health, resulting in two
      distinct stress phenotypes: coral bleaching under excess DOC and severe tissue
      sloughing (>90% tissue loss resulting in host mortality) under excess DON. These
      phenotypes were accompanied by structural changes in the Symbiodinium community.
      In contrast, the associated bacterial community remained remarkably stable and
      was dominated by two Endozoicomonas phylotypes, comprising on average 90% of 16S
      rRNA gene sequences. This dominance of Endozoicomonas even under conditions of
      coral bleaching and mortality suggests the bacterial community of P. verrucosa
      may be rather inflexible and thereby unable to respond or acclimatize to rapid
      changes in the environment, contrary to what was previously observed in other
      corals. In this light, our results suggest that coral holobionts might occupy
      structural landscapes ranging from a highly flexible to a rather inflexible
      composition with consequences for their ability to respond to environmental
      change.

PMID- 29468041
TI  - Genome-wide comparisons reveal a clinal species pattern within a holobenthic
      octopod-the Australian Southern blue-ringed octopus, Hapalochlaena maculosa
      (Cephalopoda: Octopodidae).
AB  - The southern blue-ringed octopus, Hapalochlaena maculosa (Hoyle, 1883) lacks a
      planktonic dispersal phase, yet ranges across Australia's southern coastline.
      This species' brief and holobenthic life history suggests gene flow might be
      limited, leaving distant populations prone to strong genetic divergence. This
      study used 17,523 genome-wide SNP loci to investigate genetic structuring and
      local adaptation patterns of H. maculosa among eight sampling sites along its
      reported range. Within sites, interrelatedness was very high, consistent with the
      limited dispersal of this taxon. However, inbreeding coefficients were
      proportionally lower among sites where substructuring was not detected,
      suggesting H. maculosa might possess a mechanism for inbreeding avoidance.
      Genetic divergence was extremely high among all sites, with the greatest
      divergence observed between both ends of the distribution, Fremantle, WA, and
      Stanley, TAS. Genetic distances closely followed an isolation by geographic
      distance pattern. Outlier analyses revealed distinct selection signatures at all
      sites, with the strongest divergence reported between Fremantle and the other
      Western Australian sites. Phylogenetic reconstructions using the described sister
      taxon H. fasciata (Hoyle, 1886) further supported that the genetic divergence
      between distal H. maculosa sites in this study was equivalent to that of between
      established heterospecifics within this genus. However, it is advocated that
      taxonomic delineations within this species should be made with caution. These
      data indicate that H. maculosa forms a clinal species pattern across its
      geographic range, with gene flow present through allele sharing between adjacent
      populations. Morphological investigations are recommended for a robust resolution
      of the taxonomic identity and ecotype boundaries of this species.

PMID- 29468042
TI  - Influence of damming on anuran species richness in riparian areas: A test of the
      serial discontinuity concept.
AB  - Almost all large rivers worldwide are fragmented by dams, and their impacts have
      been modeled using the serial discontinuity concept (SDC), a series of
      predictions regarding responses of key biotic and abiotic variables. We evaluated
      the effects of damming on anuran communities along a 245-km river corridor by
      conducting repeated, time-constrained anuran calling surveys at 42 locations
      along the Broad and Pacolet Rivers in South Carolina, USA. Using a hierarchical
      Bayesian analysis, we test the biodiversity prediction of the SDC (modified for
      floodplain rivers) by evaluating anuran occupancy and species diversity relative
      to dams and degree of urbanized land use. The mean response of the anuran
      community indicated that occupancy and species richness were maximized when sites
      were farther downstream from dams. Sites at the farthest distances downstream of
      dams (47.5 km) had an estimated ~3 more species than those just below dams.
      Similarly, species-specific occupancy estimates showed a trend of higher
      occupancy downstream from dams. Therefore, using empirical estimation within the
      context of a 245-km river riparian landscape, our study supports SDC predictions
      for a meandering river. We demonstrate that with increasing distance downstream
      from dams, riparian anuran communities have higher species richness. Reduced
      species richness immediately downstream of dams is likely driven by alterations
      in flow regime that reduce or eliminate flows which sustain riparian wetlands
      that serve as anuran breeding habitat. Therefore, to maintain anuran
      biodiversity, we suggest that flow regulation should be managed to ensure water
      releases inundate riparian wetlands during amphibian breeding seasons and
      aseasonal releases, which can displace adults, larvae, and eggs, are avoided.
      These outcomes could be achieved by emulating pre-dam seasonal discharge data,
      mirroring discharge of an undammed tributary within the focal watershed, or by
      basing real-time flow releases on current environmental conditions.

PMID- 29468043
TI  - The strength of negative plant-soil feedback increases from the intraspecific to
      the interspecific and the functional group level.
AB  - One of the processes that may play a key role in plant species coexistence and
      ecosystem functioning is plant-soil feedback, the effect of plants on associated
      soil communities and the resulting feedback on plant performance. Plant-soil
      feedback at the interspecific level (comparing growth on own soil with growth on
      soil from different species) has been studied extensively, while plant-soil
      feedback at the intraspecific level (comparing growth on own soil with growth on
      soil from different accessions within a species) has only recently gained
      attention. Very few studies have investigated the direction and strength of
      feedback among different taxonomic levels, and initial results have been
      inconclusive, discussing phylogeny, and morphology as possible determinants. To
      test our hypotheses that the strength of negative feedback on plant performance
      increases with increasing taxonomic level and that this relationship is explained
      by morphological similarities, we conducted a greenhouse experiment using species
      assigned to three taxonomic levels (intraspecific, interspecific, and functional
      group level). We measured certain fitness-related aboveground traits and used
      them along literature-derived traits to determine the influence of morphological
      similarities on the strength and direction of the feedback. We found that the
      average strength of negative feedback increased from the intraspecific over the
      interspecific to the functional group level. However, individual accessions and
      species differed in the direction and strength of the feedback. None of our
      results could be explained by morphological dissimilarities or individual traits.
      Synthesis. Our results indicate that negative plant-soil feedback is stronger if
      the involved plants belong to more distantly related species. We conclude that
      the taxonomic level is an important factor in the maintenance of plant
      coexistence with plant-soil feedback as a potential stabilizing mechanism and
      should be addressed explicitly in coexistence research, while the traits
      considered here seem to play a minor role.

PMID- 29468044
TI  - Low rates of hybridization between European wildcats and domestic cats in a human
      dominated landscape.
AB  - Hybridization between wild species and their domestic congeners is considered a
      major threat for wildlife conservation. Genetic integrity of the European
      wildcat, for instance, is a concern as they are outnumbered by domestic cats by
      several orders of magnitude throughout its range. We genotyped 1,071 individual
      wildcat samples obtained from hair traps and roadkills collected across the
      highly fragmented forests of western Central Europe, in Germany and Luxembourg,
      to assess domestic cat introgression in wildcats in human-dominated landscapes.
      Analyses using a panel of 75 autosomal SNPs suggested a low hybridization rate,
      with 3.5% of wildcat individuals being categorized as F1, F2, or backcrosses to
      either parental taxon. We report that results based on a set of SNPs were more
      consistent than on a set of 14 microsatellite markers, showed higher accuracy to
      detect hybrids and their class in simulation analyses, and were less affected by
      underlying population structure. Our results strongly suggest that very high
      hybridization rates previously reported for Central Europe may be partly due to
      inadequate choice of markers and/or sampling design. Our study documents that an
      adequately selected SNP panel for hybrid detection may be used as an alternative
      to commonly applied microsatellite markers, including studies relying on
      noninvasively collected samples. In addition, our finding of overall low
      hybridization rates in Central European wildcats provides an example of
      successful wildlife coexistence in human-dominated, fragmented landscapes.

PMID- 29468045
TI  - An interaction-driven cannibalistic reaction norm.
AB  - Cannibalism is induced in larval-stage populations of the Hokkaido salamander,
      Hynobius retardatus, under the control of a cannibalism reaction norm. Here, I
      examined phenotypic expression under the cannibalism reaction norm, and how the
      induction of a cannibalistic morph under the norm leads to populational
      morphological diversification. I conducted a set of experiments in which density
      was manipulated to be either low or high. In the high-density treatment, the
      populations become dimorphic with some individuals developing into the cannibal
      morph type. I performed an exploratory analysis based on geometric morphometrics
      and showed that shape characteristics differed between not only cannibal and
      noncannibal morph types in the high-density treatment but also between those
      morph types and the solitary morph type in the low-density treatment. Size and
      shape of cannibal and noncannibal individuals were found to be located at either
      end of a continuum of expression following a unique size-shape integration rule
      that was different from the rule governing the size and shape variations of the
      solitary morph type. This result implies that the high-density-driven inducible
      morphology of an individual is governed by a common integration rule during the
      development of dimorphism under the control of the cannibalism reaction norm.
      Phenotypic expression under the cannibalism reaction norm is driven not only by
      population density but also by social interactions among the members of a
      population: variation in the populational expression of dimorphism is associated
      with contingent social interaction events among population members. The induced
      cannibalistic morph thus reflects not only by contest-type exploitative
      competition but also interference competition.

PMID- 29468046
TI  - Rapid identification of the Asian gypsy moth and its related species based on
      mitochondrial DNA.
AB  - The gypsy moth-Lymantria dispar (Linnaeus)-is a worldwide forest defoliator and
      is of two types: the European gypsy moth and the Asian gypsy moth. Because of
      multiple invasions of the Asian gypsy moth, the North American Plant Protection
      Organization officially approved Regional Standards for Phytosanitary Measures
      No. 33. Accordingly, special quarantine measures have been implemented for 30
      special focused ports in the epidemic areas of the Asian gypsy moth, including
      China, which has imposed great inconvenience on export trade. The Asian gypsy
      moth and its related species (i.e., Lymantria monocha and Lymantria xylina)
      intercepted at ports are usually at different life stages, making their
      identification difficult. Furthermore, Port quarantine requires speedy clearance.
      As such, it is difficult to identify the Asian gypsy moth and its related species
      only by their morphological characteristics in a speedy measure. Therefore, this
      study aimed to use molecular biology technology to rapidly identify the Asian
      gypsy moth and its related species based on the consistency of mitochondrial DNA
      in different life stages. We designed 10 pairs of specific primers from different
      fragments of the Asian gypsy moth and its related species, and their detection
      sensitivity met the need for rapid identification. In addition, we determined the
      optimal polymerase chain reaction amplification temperature of the 10 pairs of
      specific primers, including three pairs of specific primers for the Asian gypsy
      moth (L. dispar asiatic), four pairs of specific primers for the nun moth (L.
      monocha), and three pairs of specific primers for the casuarina moth (L. xylina).
      In conclusion, using our designed primers, direct rapid identification of the
      Asian gypsy moth and its related species is possible, and this advancement can
      help improve export trade in China.

PMID- 29468047
TI  - Exploring the phylogeography of a hexaploid freshwater fish by RAD sequencing.
AB  - The KwaZulu-Natal yellowfish (Labeobarbus natalensis) is an abundant cyprinid,
      endemic to KwaZulu-Natal Province, South Africa. In this study, we developed a
      single-nucleotide polymorphism (SNP) dataset from double-digest restriction site
      associated DNA (ddRAD) sequencing of samples across the distribution. We
      addressed several hidden challenges, primarily focusing on proper filtering of
      RAD data and selecting optimal parameters for data processing in polyploid
      lineages. We used the resulting high-quality SNP dataset to investigate the
      population genetic structure of L. natalensis. A small number of mitochondrial
      markers present in these data had disproportionate influence on the recovered
      genetic structure. The presence of singleton SNPs also confounded genetic
      structure. We found a well-supported division into northern and southern
      lineages, with further subdivision into five populations, one of which reflects
      north-south admixture. Approximate Bayesian Computation scenario testing
      supported a scenario where an ancestral population diverged into northern and
      southern lineages, which then diverged to yield the current five populations. All
      river systems showed similar levels of genetic diversity, which appears unrelated
      to drainage system size. Nucleotide diversity was highest in the smallest river
      system, the Mbokodweni, which, together with adjacent small coastal systems,
      should be considered as a key catchment for conservation.

PMID- 29468048
TI  - A novel sperm adaptation to evolutionary constraints on reproduction: Pre
      ejaculatory sperm activation in the beach spawning capelin (Osmeridae).
AB  - Reproduction of external fertilizing vertebrates is typically constrained to
      either fresh or salt water, not both. For all studied amphibians and fishes, this
      constraint includes immotile sperm that are activated after ejaculation only by
      the specific chemistry of the fertilizing medium in which the species evolved
      (fresh, brackish, or salt water). No amphibians can reproduce in the sea.
      Although diadromous fishes may migrate between salt and fresh water, they are
      shackled to their natal environment for spawning in part because of sperm
      activation. Here, we report for the first time among all documented external
      fertilizing vertebrates, that in the absence of any external media, sperm are
      motile at ejaculation in a marine spawning fish (Osmeridae, capelin, Mallotus
      villosus). To illuminate why, we evaluated sperm behavior at different salinities
      in M. villosus as well as the related freshwater spawning anadromous rainbow
      smelt (Osmerus mordax). Surprisingly, sperm performance was superior in fresh
      water for both species. M. villosus spend their entire life at sea but our
      results show that their sperm are deactivated by sea water, suggesting a
      freshwater ancestry. By circumventing constraining water chemistry, we interpret
      the unique pre-ejaculatory sperm activation in this species as a novel adaptation
      that enables fertilization in the marine environment. These findings also
      contribute to understanding the persistence of anadromy, despite great energetic
      costs to adult fishes.

PMID- 29468049
TI  - Sea ice meiofauna distribution on local to pan-Arctic scales.
AB  - Arctic sea ice provides microhabitats for biota that inhabit the liquid-filled
      network of brine channels and the ice-water interface. We used meta-analysis of
      23 published and unpublished datasets comprising 721 ice cores to synthesize the
      variability in composition and abundance of sea ice meiofauna at spatial scales
      ranging from within a single ice core to pan-Arctic and seasonal scales. Two
      thirds of meiofauna individuals occurred in the bottom 10 cm of the ice. Locally,
      replicate cores taken within meters of each other were broadly similar in
      meiofauna composition and abundance, while those a few km apart varied more; 75%
      of variation was explained by station. At the regional scale (Bering Sea first
      year ice), meiofauna abundance varied over two orders of magnitude. At the pan
      Arctic scale, the same phyla were found across the region, with taxa that have
      resting stages or tolerance to extreme conditions (e.g., nematodes and rotifers)
      dominating abundances. Meroplankton, however, was restricted to nearshore
      locations and landfast sea ice. Light availability, ice thickness, and distance
      from land were significant predictor variables for community composition on
      different scales. On a seasonal scale, abundances varied broadly for all taxa and
      in relation to the annual ice algal bloom cycle in both landfast and pack ice.
      Documentation of ice biota composition, abundance, and natural variability is
      critical for evaluating responses to decline in Arctic sea ice. Consistent
      methodology and protocols must be established for comparability of meiofauna
      monitoring across the Arctic. We recommend to (1) increase taxonomic resolution
      of sea ice meiofauna, (2) focus sampling on times of peak abundance when seasonal
      sampling is impossible, (3) include the bottom 30 cm of ice cores rather than
      only bottom 10 cm, (4) preserve specimens for molecular analysis to improve
      taxonomic resolution, and (5) formulate a trait-based framework that relates to
      ecosystem functioning.

PMID- 29468050
TI  - Functional macronutritional generalism in a large omnivore, the brown bear.
AB  - We combine a recently developed framework for describing dietary generalism with
      compositional data analysis to examine patterns of omnivory in a large widely
      distributed mammal. Using the brown bear (Ursus arctos) as a model species, we
      collected and analyzed data from the literature to estimate the proportions of
      macronutrients (protein, carbohydrate, and lipid) in the diets of bear
      populations. Across their range, bears consumed a diversity of foods that
      resulted in annual population diets that varied in macronutrient proportions,
      suggesting a wide fundamental macronutrient niche. The variance matrix of
      pairwise macronutrient log-ratios indicated that the most variable macronutrient
      among diets was carbohydrate, while protein and lipid were more proportional or
      codependent (i.e., relatively more constant log-ratios). Populations that
      consumed anthropogenic foods, such agricultural crops and supplementary feed
      (e.g., corn), had a higher geometric mean proportion of carbohydrate, and lower
      proportion of protein, in annual diets. Seasonally, mean diets were lower in
      protein and higher in carbohydrate, during autumn compared to spring. Populations
      with anthropogenic subsidies, however, had higher mean proportions of
      carbohydrate and lower protein, across seasons compared to populations with
      natural diets. Proportions of macronutrients similar to those selected in
      experiments by captive brown bears, and which optimized primarily fat mass gain,
      were observed among hyperphagic prehibernation autumn diets. However, the
      majority of these were from populations consuming anthropogenic foods, while
      diets of natural populations were more variable and typically higher in protein.
      Some anthropogenic diets were close to the proportions selected by captive bears
      during summer. Our results suggest that omnivory in brown bears is a functional
      adaptation enabling them to occupy a diverse range of habitats and tolerate
      variation in the nutritional composition and availability of food resources.
      Furthermore, we show that populations consuming human-sourced foods have
      different dietary macronutrient proportions relative to populations with natural
      diets.

PMID- 29468051
TI  - The knowledge, attitudes and practices of doctors regarding antibiotic resistance
      at a tertiary care institution in the Caribbean.
AB  - Background: Antibiotic resistance (ABR) is a serious threat that requires
      coordinated global intervention to prevent its spread. There is limited data from
      the English-speaking Caribbean. Methods: As part of a national programme to
      address antibiotic resistance in Jamaica, a survey of the knowledge, attitudes
      and antibiotic prescribing practices of Jamaican physicians was conducted using a
      32-item self-administered questionnaire. Results: Of the eight hundred physicians
      targeted, 87% responded. The majority thought the problem of resistance very
      important globally (82%), less nationally (73%) and even less (53%) in personal
      practices. Hospital physicians were more likely to consider antibiotic resistance
      important in their practice compared to those in outpatient practice or both (p <
      0.001). Composite knowledge scores were generated and considered good if scored >
      80%, average if 60-79% and poor if < 60%. Most had good knowledge of factors
      preventing resistance (83%) and resistance inducing potential of specific
      antibiotics (59%), but only average knowledge of factors contributing to
      resistance (57%). Knowledge of preventative factors was highest in females (p =
      0.004), those with postgraduate training (p = 0.001) and those > four years post
      graduation (p = 0.03). Empiric therapy was often directed by international
      guidelines and cultures were not routinely done. Limited laboratory and human
      resources were identified as challenges. Conclusion: Physicians in this study
      were aware of the problem of ABR, but downplayed its significance nationally and
      personally. These results will guide a national antibiotic stewardship programme.

PMID- 29468052
TI  - Prevalence of Staphylococcus spp. nasal colonization among doctors of podiatric
      medicine and associated risk factors in Spain.
AB  - Background: This study aimed to estimate the prevalence of methicillin
      susceptible and -resistant Staphylococcus aureus (MSSA and MRSA) and methicillin
      resistant Staphylococcus epidermidis (MRSE) nasopharyngeal carriage among Doctors
      of Podiatric Medicine (Podiatrists) and to determine the potential risk factors.
      Methods: A cross-sectional study was carried out in 2016-2017 among 239
      podiatrists in Spain. The presence of MSSA, MRSA, and MRSE was determined by
      microbiological analysis of nasal exudate and antimicrobial susceptibility was
      determined. Each podiatrist completed a questionnaire. The questionnaire
      comprised various parameters such as sex, age, podiatry experience duration,
      underlying diseases, prior antibiotic treatment, hospitalization during the last
      year, and use of a protective mask, an aspiration system, or gloves. Results: The
      prevalence of MSSA, MRSA, and MRSE was 23.0%, 1.3%, and 23.8%, respectively. The
      MSSA prevalence was higher among podiatrists who did not use an aspiration system
      (32.3%) compared to those who did (19.3%; p = 0.0305), and among podiatrists with
      respiratory diseases (36.8%) compared to those without (20.8%; p = 0.0272). The
      MRSE prevalence was higher among men (33.7%) compared to women (8.6%; p =
      0.0089), podiatrists aged >=50 (38.5%) compared to <=35 (17.8%; p = 0.0101), and
      podiatrists with >=15 (39.3%) compared to <=5 years of podiatry experience
      (12.5%; p = 0.0015). Among the S. aureus strains, 84.5% were resistant to
      penicillin, 22.4% to erythromycin, 20.7% to clindamycin, and 12.7% to mupirocin.
      The MRSE strains were resistant to penicillin (93.0%), erythromycin (78.9%), and
      mupirocin (73.7%). Conclusions: The prevalence of S. aureus and S. epidermidis
      nasal carriage is low among Spanish podiatrists compared to other health
      professionals.

PMID- 29468053
TI  - APSIC guidelines for disinfection and sterilization of instruments in health care
      facilities.
AB  - Background: The Asia Pacific Society of Infection Control launched its revised
      Guidelines for Disinfection and Sterilization of Instruments in Health Care
      Facilities in February 2017. This document describes the guidelines and
      recommendations for the reprocessing of instruments in healthcare setting. It
      aims to highlight practical recommendations in a concise format designed to
      assist healthcare facilities at Asia Pacific region in achieving high standards
      in sterilization and disinfection. Method: The guidelines were revised by an
      appointed workgroup comprising experts in the Asia Pacific region, following
      reviews of previously published guidelines and recommendations relevant to each
      section. Results: It recommends the centralization of reprocessing, training of
      all staff with annual competency assessment, verification of cleaning, continual
      monitoring of reprocessing procedures to ensure their quality and a corporate
      strategy for dealing with single-use and single-patient use medical
      equipment/devices. Detailed recommendations are also given with respect to
      reprocessing of endoscopes. Close working with the Infection Prevention & Control
      department is also recommended where decisions related to reprocessing medical
      equipment/devices are to be made. Conclusions: Sterilization facilities should
      aim for excellence in practices as this is part of patient safety. The guidelines
      that come with a checklist help service providers identify gaps for improvement
      to reach this goal.

PMID- 29468054
TI  - In vitro activity of ivermectin against Staphylococcus aureus clinical isolates.
AB  - Background: Ivermectin is an endectocide against many parasites. Though being a
      macrocyclic lactone, its activity against bacteria has been less known, possibly
      due to the fact that micromolar concentrations at tissue levels are required to
      achieve a therapeutic effect. Among pathogenic bacteria of major medical
      significance, Staphylococcus aureus cause a number of diseases in a wide variety
      of hosts including humans and animals. It has been attributed as one of the most
      pathogenic organisms. The emergence of methicillin resistance has made the
      treatment of S. aureus even more difficult as it is now resistant to most of the
      available antibiotics. Thus, search for alternate anti-staphylococcal agents
      requires immediate attention. Methods: Twenty-one clinical isolates of S. aureus
      were isolated from bovine milk collected from Lahore and Faisalabad Pakistan.
      Different anthelmintics including levamisole, albendazole and ivermectin were
      tested against S. aureus to determine their minimum inhibitory concentrations.
      This was followed-up by growth curve analysis, spot assay and time-kill kinetics.
      Results: The results showed that ivermectin but not levamisole or albendazole
      exhibited a potent anti-staphylococcal activity at the concentrations of 6.25 and
      12.5 MUg/ml against two isolates. Interestingly, one of the isolate was sensitive
      while the other was resistant to methicillin/cefoxitin. Conclusions: Our novel
      findings indicate that ivermectin has an anti-bacterial effect against certain S.
      aureus isolates. However, to comprehend why ivermectin did not inhibit the growth
      of all Staphylococci needs further investigation. Nevertheless, we have extended
      the broad range of known pharmacological effects of ivermectin. As pharmacology
      and toxicology of ivermectin are well known, its further development as an anti
      staphylococcal agent is potentially appealing.

PMID- 29468055
TI  - Comparison of governance approaches for the control of antimicrobial resistance:
      Analysis of three European countries.
AB  - Policy makers and governments are calling for coordination to address the crisis
      emerging from the ineffectiveness of current antibiotics and stagnated pipe-line
      of new ones - antimicrobial resistance (AMR). Wider contextual drivers and
      mechanisms are contributing to shifts in governance strategies in health care,
      but are national health system approaches aligned with strategies required to
      tackle antimicrobial resistance? This article provides an analysis of governance
      approaches within healthcare systems including: priority setting, performance
      monitoring and accountability for AMR prevention in three European countries:
      England, France and Germany. Advantages and unresolved issues from these
      different experiences are reported, concluding that mechanisms are needed to
      support partnerships between healthcare professionals and patients with
      democratized decision-making and accountability via collaboration. But along with
      this multi-stakeholder approach to governance, a balance between regulation and
      persuasion is needed.

PMID- 29468056
TI  - Implementation of universal rapid human immunodeficiency virus screening on labor
      and delivery.
AB  - Background: A case of mother to child transmission (MTCT) of HIV at a medical
      center in Washington, DC, resulted in the implementation of universal opt-out
      rapid testing of patients admitted for delivery. This article evaluates the
      policy's efficacy and implementation. Methods: We evaluated the implementation
      using the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM)
      framework. Results: We could not evaluate decrease in MTCT rate secondary to low
      sample size (n = 3324) and no true-positive results. Patients not tested (n =
      458) were predominately secondary to physician omission (93.7%) and were more
      likely to be White (p < 0.01) and older (p < 0.01). There was a negative
      relationship with physician omission over time. Conclusion: The policy was
      successfully implemented with decreasing proportions of patients not tested.
      Earlier inclusion of testing into standard admission orders and nurse-based
      approach may have expedited adoption. Given the low incidence of new HIV
      diagnosis in labor, we were unable to assess decrease in MTCT.

PMID- 29468057
TI  - Utility of convex EUS for preoperative vascular evaluation of malignant biliary
      tract neoplasm.
AB  - The aim of the present study was to examine the utility of convex endoscopic
      ultrasonography (EUS) for the preoperative vascular evaluation of malignant
      biliary tract neoplasm, by comparing EUS findings with histological findings from
      resected specimens. Between January 2008 and January 2016, the present study
      retrospectively retrieved 82 cases diagnosed with malignant biliary tract
      neoplasm to compare findings from convex EUS with histological findings from
      resected specimens. A total of four groups were defined according to the results
      of EUS of the hepatic artery (HA) and portal vein (PV): Group 1, hyperechoic
      tissue between tumor and vessel; group 2, close proximity between tumor and
      vessel without loss of hyperechoic tissue; group 3, tumor and vessel contiguity,
      with loss of hyperechoic tissue; and group 4, encasement >180 degrees . Regarding
      the HA, all 17 cases in groups 2 and 3 in which the tumor was close to the HA
      however no obvious encasement was evident, demonstrated no histological invasion,
      or the HA could be separated from the tumor intraoperatively. However, this was
      not the case for the portal vein. Of the six cases in group 3, 4 cases (66.7%)
      demonstrated PV invasion. Overall, convex EUS is useful for the preoperative
      evaluation of malignant biliary tract neoplasms, and surgery may be considered
      when the tumor is close to the HA on computed tomography scans, however there is
      no obvious encasement visualized by convex EUS.

PMID- 29468058
TI  - A patient with MEN1 and end-stage chronic kidney disease due to Alport syndrome:
      Decision making on the eligibility of transplantation.
AB  - Absence of neoplastic disease in the organ-recipient is required in order to
      allow organ transplantation. Due to its rarity, no data regarding management of
      patients with Multiple endocrine neoplasia type 1 (MEN1) and end-stage renal
      failure candidates for kidney transplantation are available. A 36 year-old man
      was referred to the present hospital with MEN1, with a neuroendocrine pancreatic
      tumor and primary hyperparathyroidism and associated Alport syndrome with end
      stage renal failure. The present study aimed to establish the eligibility of the
      patient for a kidney transplantation. The neuroendocrine tumor had been treated
      with duodenopancreatectomy two years earlier and hyperparathyroidism by
      parathyroidectomy. The review of the literature did not provide data regarding
      the eligibility for kidney transplantation of patients harboring a neuroendocrine
      pancreatic tumor in the context of MEN1. Due to the end-stage renal failure,
      neuroendocrine markers were unreliable and the investigation therefore relied on
      imaging studies, which were unremarkable. Young age, low-grade tumor, low
      expression of Ki67, absence of metastatic lymph nodes, onset in the setting of a
      MEN1 were all positive prognostic factors of the neuroendocrine tumor. Normal
      serum calcium ruled out persistent primary hyperparathyroidism. Overall,
      hemodyalisis is known to significantly reduce life expectancy. Benefits of kidney
      transplantation overcome the risk of neuroendocrine tumor recurrence in a young
      patient bearing MEN1.

PMID- 29468059
TI  - Oxaliplatin-induced hepatic sinusoidal obstruction syndrome in a patient with
      gastric cancer: A case report.
AB  - Oxaliplatin is a platinum-based antineoplastic agent used in cancer chemotherapy.
      Oxaliplatin-induced hepatic sinusoidal obstruction syndrome (HSOS) has been
      reported in the context of chemotherapy for liver metastasis of colorectal
      cancer. However, to the best of our knowledge, there is no report of oxaliplatin
      associated HSOS in patients with gastric cancer. The present study reported a
      patient with gastric cancer who received proximal gastrectomy and oxaliplatin
      containing chemotherapy. Contrast-enhanced computed tomography revealed that
      liver parenchyma appeared heterogeneous and demonstrated hypoattenuation in the
      portal phase. In dynamic contrast-enhanced magnetic resonance imaging,
      hypointense heterogeneity was demonstrated in the portal-venous phase.
      Pathological examination indicated distinctive multifocal sinusoidal dilatation.
      In conclusion, the present report indicated a case of oxaliplatin-induced HSOS in
      a patient with gastric cancer who received oxaliplatin-contained chemotherapy.

PMID- 29468060
TI  - Identification of i(X)(p10) as the sole molecular abnormality in atypical chronic
      myeloid leukemia evolved into acute myeloid leukemia.
AB  - The World Health Organization classifies atypical chronic myeloid leukemia (aCML)
      as a myeloproliferative/myelodisplastic hematological disorder. The primary
      manifestations are leukocytosis with disgranulopoiesis, absence of basophilia
      and/or monocytosis, splenomegaly and absence of Philadelphia chromosome or
      BCR/ABL fusion. Overall 50-65% of patients demonstrate karyotypic abnormalities,
      although no specific cytogenetic alterations have been associated with this
      disease. X chromosome alterations have been rarely reported in myeloid
      malignancies. Although Isodicentric X, idic(X)(q13) is well known in females with
      myelodysplastic syndromes (MDS), little data are available on X isochromosome and
      its pathogenetic potential in these disorders. i(X)(p10) is observed in a variety
      of hematologic malignancies, both myeloid and lymphoid, as a unique abnormality,
      as well as part of a more complex karyotype, in females and less frequently in
      male patients. The present report describes the first patient with aCML, with
      documented isolated i(X)(p10), who developed a secondary acute myeloid leukemia
      (sAML).

PMID- 29468061
TI  - Plasma interleukin-8 levels are persistently elevated for 1 month after minimally
      invasive colorectal resection for colorectal cancer.
AB  - Minimally invasive colorectal resection (MICR) for colorectal cancer (CRC) is
      associated with elevated levels of seven proangiogenic proteins that persist for
      2-4 weeks after surgery. The proangiogenic plasma may promote tumor growth
      postoperatively in patients with residual cancer. To the best of our knowledge,
      the impact of surgery on interleukin 8 (IL-8) levels is unknown. The aim of the
      present study was to evaluate plasma IL-8 levels after MICR for CRC. Patients
      with CRC enrolled in an institutional review board-approved plasma/data bank who
      underwent MICR were eligible. Blood samples were taken preoperatively (preop) and
      at multiple postoperative (postop) time points, and were stored at -80 degrees C.
      Only patients for whom preop, postop day (POD) 1, POD 3 and at least 1 late
      postop plasma samples (POD7-34) available were enrolled. Clinical, demographical
      and pathological data were collected. IL-8 levels were determined via ELISA and
      results were reported as the mean and +/- standard deviation. The Wilcoxon signed
      rank test was used for analysis with P<0.05 used as the significance threshold. A
      total of 73 CRC patients (colon, 62%; rectal, 38%) who underwent MICR
      (laparoscopic-assisted, 60%; hand-assisted, 40%) were studied. The mean preop IL
      8 level was 20.4+/-10.6 pg/ml. Significant elevations in plasma IL-8 levels were
      noted compared with preop levels on POD1 (43.1+/-38.6; n=72; P<0.0001), POD 3
      (33.0+/-30.1; n=71; P<0.0001), POD7-13 (29.9+/-21.9; n=50; P<0.0001), POD14-20
      (33.1+/-18.3; n=24; P=0.002), and for the POD21-27 time point (24.0+/-9.2; n=16;
      P=0.002). In conclusion, plasma IL-8 levels were significantly elevated from
      baseline for 4 weeks after MICR for CRC. In conjunction with the other
      proangiogenic MICR-associated blood compositional changes, increased IL-8 levels
      may promote tumor angiogenesis and growth postop.

PMID- 29468062
TI  - Characterization of oncogene suppressor marker expression in patients with
      submucosal gastric carcinoma.
AB  - The aim of the present study was to determine the clinical significance of p53
      and p21ras p21wafl, p27kip1 and p16ink4a expression in cases of early gastric
      cancer. A total of 81 patients who had undergone gastrectomy with D2
      lymphadenectomy between 1971 and 2004 were retrospectively investigated. The
      immunohistochemical expression of p21ras, p53, p21waf1/cip1, p27kip1 and p16ink4a
      in the tissues was evaluated. In normal, metaplastic and tumoral mucosa, p53 was
      positive in 53, 87.3, and 87.1% of the cases, respectively. In the same tissues,
      p21ras was positivE in 85.3, 86 and 96.8%, respectively. Positivity FOR p16ink4a
      was DETECTED IN 46.3, 91.1 and 86% OF THE CASES, respectively, WHEREAS p27kip1
      WAS positiVE IN 60, 94.7 and 95.3%, and p21wafl/cip1 WAS positivE IN 32.4, 72.7
      and 71.4% OF THE CASES, respectively. All THE tumors WERE positive for p53.
      Tumors with lymph node invasion presented WITH OVERexpression (+4) of p53 in 47%
      of the cases VS. 17% OF patients who DID not HAVE lymph node involvement.
      THEREFORE, higher expression of p53, p21ras and p21wafl/cip1 IN the tumor
      exhibited a statistically significant association with lymph node involvement.

PMID- 29468063
TI  - Effects of metformin on survival outcomes of pancreatic cancer patients with
      diabetes: A meta-analysis.
AB  - Pancreatic cancer risk is reduced by metformin treatment in patients with
      diabetes. However, the effect of metformin on pancreatic cancer overall survival
      is unclear. The aim of the present study was to determine the association between
      metformin and clinical outcomes of pancreatic cancer patients with diabetes. An
      electronic and manual search was conducted using PubMed, Web of Science, Medline
      Ovid and Cochrane Library databases between the beginning and March 31, 2017. A
      total of 8 studies consisting of 4,293 patients with pancreatic cancer with
      diabetes were included, comprising 2,033 patients who had received metformin and
      2,260 patients who had not. The meta-analysis showed that metformin was
      associated with a relative survival benefit in pancreatic cancer patients [hazard
      ratio (HR), 0.81; 95% confidence interval (CI), 0.70-0.93]. These associations
      were also observed in subgroups of Asian countries 0.64 (95% CI, 0.52-0.80) and
      Western countries 0.88 (95% CI, 0.82-0.95), as well as diabetes (no indication of
      diabetes type). Excluding the studies considered as be prone to immortal time
      bias resulted in HRs (95% CIs) of 0.86 (0.69-1.07). The results of this study
      support the notion that the use of metformin may improve the overall survival of
      patients with pancreatic cancer with concurrent diabetes. However, the proposed
      beneficial effect of metformin on pancreatic cancer survival may be based on
      immortal time bias. Further carefully designed studies with high quality are
      warranted to confirm this efficacy.

PMID- 29468064
TI  - The multiple faces of Langerhans cell histiocytosis in childhood: A gentle
      reminder.
AB  - Langerhans cell histiocytosis (LCH) is a rare hematologic disorder that results
      from the clonal multiplication and accumulation of immature dendritic Langerhans
      cells. Its reported incidence rate varies, but is considered to be 2.6-8.9 per
      million children who are <15 years of age each year. It may affect any system or
      organ. The present study reported 4 pediatric LCH cases in order to highlight the
      heterogeneity of the initial presentation, and the pitfalls that may mislead
      clinicians and delay diagnosis. The clinical features, as well as the
      pathognomonic imaging, pathology findings and treatment options were presented.
      LCH may be rare, but it should always be included in the differential diagnosis
      of persistent eczema, unexplained skin lesions, diabetes insipidus and persistent
      bone pain, among others. While the debate on pathogenesis and treatment is
      ongoing, high index of suspicion among pediatricians, pediatric oncologists and
      other specialists (pathologists, dermatologists, orthopaedic surgeons, general
      practitioners or family physicians) is essential for early diagnosis, and optimal
      outcome.

PMID- 29468065
TI  - Neuroimaging in bulimia nervosa and binge eating disorder: a systematic review.
AB  - Objective: In recent decades there has been growing interest in the use of
      neuroimaging techniques to explore the structural and functional brain changes
      that take place in those with eating disorders. However, to date, the majority of
      research has focused on patients with anorexia nervosa. This systematic review
      addresses a gap in the literature by providing an examination of the published
      literature on the neurobiology of individuals who binge eat; specifically,
      individuals with bulimia nervosa (BN) and binge eating disorder (BED). Methods: A
      systematic review was conducted in accordance with PRISMA guidelines using
      PubMed, PsycInfo, Medline and Web of Science, and additional hand searches
      through reference lists. 1,003 papers were identified in the database search.
      Published studies were included if they were an original research paper written
      in English; studied humans only; used samples of participants with a diagnosed
      eating disorder characterised by recurrent binge eating; included a healthy
      control sample; and reported group comparisons between clinical groups and
      healthy control groups. Results: Thirty-two papers were included in the
      systematic review. Significant heterogeneity in the methods used in the included
      papers coupled with small sample sizes impeded the interpretation of results.
      Twenty-one papers utilised functional Magnetic Resonance Imaging (fMRI); seven
      papers utilized Magnetic Resonance Imaging (MRI) with one of these using both MRI
      and Positron Emission Technology (PET); three studies used Single-Photon Emission
      Computed Tomography (SPECT) and one study used PET only. A small number of
      consistent findings emerged in individuals in the acute phase of illness with BN
      or BED including: volume reduction and increases across a range of areas;
      hypoactivity in the frontostriatal circuits; and aberrant responses in the
      insula, amygdala, middle frontal gyrus and occipital cortex to a range of
      different stimuli or tasks; a link between illness severity in BN and neural
      changes; diminished attentional capacity and early learning; and in SPECT
      studies, increased rCBF in relation to disorder-related stimuli. Conclusions:
      Studies included in this review are heterogenous, preventing many robust
      conclusions from being drawn. The precise neurobiology of BN and BED remains
      unclear and ongoing, large-scale investigations are required. One clear finding
      is that illness severity, exclusively defined as the frequency of binge eating or
      bulimic episodes, is related to greater neural changes. The results of this
      review indicate additional research is required, particularly extending findings
      of reduced cortical volumes and diminished activity in regions associated with
      self-regulation (frontostriatal circuits) and further exploring responses to
      disorder-related stimuli in people with BN and BED.

PMID- 29468066
TI  - Evaluation of lipid profiles and hematological parameters in hypertensive
      patients: Laboratory-based cross-sectional study.
AB  - Introduction: Hypertension and dyslipidemia are the two coexisting and
      synergizing major risk factors for cardiovascular diseases. The cellular
      constituents of blood affect the volume and viscosity of blood, thus playing a
      key role in regulating blood pressure. Overweight and obesity are key
      determinants of adverse metabolic changes including an increase in blood
      pressure. The aim of this study was to evaluate lipid profiles and hematological
      parameters in hypertensive patients at Debre Markos Referral Hospital, Northwest
      Ethiopia. Methods: Laboratory-based cross-sectional study was conducted in 100
      eligible hypertensive patients at the hospital. The required amount of blood was
      withdrawn from the patients by healthcare professionals for immediate automated
      laboratory analyses. Data were collected on socio-demographic factors,
      anthropometric measurements, blood pressure, lipid profiles, and hematological
      parameters. Result: The mean serum levels of triglyceride, total cholesterol, and
      low-density lipoprotein were significantly higher than their respective cut-off
      values in the hypertensive patients. Besides, 54%, 52%, 35%, and 11% of the
      hypertensive patients had abnormal low-density lipoprotein, total cholesterol,
      triglyceride, and high-density lipoprotein levels, respectively. Higher levels of
      low-density lipoprotein, hemoglobin, and red blood cell count were observed in
      the hypertensive patients whose blood pressure had been poorly controlled than
      the controlled ones (p < 0.05). Waist circumference had a significant positive
      association with the serum levels of total cholesterol and white blood cell count
      (p < 0.05). Conclusion: Hypertensive patients had a high prevalence of lipid
      profile abnormalities and poorly controlled blood pressure which synergize in
      accelerating other cardiovascular diseases. Some hematological parameters such as
      red blood cell count are also increased as do the severity of hypertension.

PMID- 29468067
TI  - Pharyngeal dysphagia due to Varicella zoster virus meningoradiculitis and full
      recovery: Case report and endoscopic findings.
AB  - Varicella zoster virus reactivation is a rare cause of pharyngeal dysphagia with
      long-term sequelae persisting in most cases. A 76-year-old immunocompetent woman
      presented with a 4-week history of dysphagia and dysphonia. Brain magnetic
      resonance imaging displayed a negative finding. Fiberoptic endoscopic evaluation
      of swallowing showed a severe dysphagia leading to a percutaneous gastrostomy
      eventually. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis and
      polymerase chain reaction amplified Varicella zoster virus DNA. Eight months
      after Acyclovir treatment and despite a persisting impairment of the recurrent
      laryngeal nerve, regular swallowing function was regained and percutaneous
      gastrostomy could be removed.

PMID- 29468068
TI  - A case report of thrombosed varicosities of pubic collateral veins: Ideal
      treatment strategy and contribution of era imaging technologies in diagnosis.
AB  - Collateral circulation is an alternative path occurring in case of venous or
      artery obstruction. This path may usually develop after primary recanalization.
      In our case, a 62-year-old woman presented to our Emergency Department
      complaining about a suprapubic swelling with a cyanotic discoloration of the
      overlying skin for the past 10 days for which she had been previously prescribed
      antibiotics. Investigation with ultrasound and contrast-enhanced computed
      tomography was performed. An imaging study revealed thrombosed pubic varicose
      collateral veins due to deep vein obstruction and occlusion of the left external
      iliac vein. The patient was treated with low-molecular-weight heparin, and
      swelling subsided gradually. Collateral veins of the abdominal wall and over the
      pubic tubercle are highly predictive of deep venous obstructive disease proximal
      to the groin level. These collaterals should never be removed, and the patient
      should be subjected to a diligent laboratory and imaging investigation.

PMID- 29468069
TI  - Utility of SOFA score, management and outcomes of sepsis in Southeast Asia: a
      multinational multicenter prospective observational study.
AB  - Background: Sepsis is a global threat but insufficiently studied in Southeast
      Asia. The objective was to evaluate management, outcomes, adherence to sepsis
      bundles, and mortality prediction of maximum Sequential Organ Failure Assessment
      (SOFA) scores in patients with community-acquired sepsis in Southeast Asia.
      Methods: We prospectively recruited hospitalized adults within 24 h of admission
      with community-acquired infection at nine public hospitals in Indonesia (n = 3),
      Thailand (n = 3), and Vietnam (n = 3). In patients with organ dysfunction (total
      SOFA score >= 2), we analyzed sepsis management and outcomes and evaluated
      mortality prediction of the SOFA scores. Organ failure was defined as the maximum
      SOFA score >= 3 for an individual organ system. Results: From December 2013 to
      December 2015, 454 adult patients presenting with community-acquired sepsis due
      to diverse etiologies were enrolled. Compliance with sepsis bundles within 24 h
      of admission was low: broad-spectrum antibiotics in 76% (344/454), >= 1500 mL
      fluid in 50% of patients with hypotension or lactate >= 4 mmol/L (115/231), and
      adrenergic agents in 71% of patients with hypotension (135/191). Three hundred
      and fifty-five patients (78%) were managed outside of ICUs. Ninety-nine patients
      (22%) died. Total SOFA score on admission of those who subsequently died was
      significantly higher than that of those who survived (6.7 vs. 4.6, p < 0.001).
      The number of organ failures showed a significant correlation with 28-day
      mortality, which ranged from 7% in patients without any organ failure to 47% in
      those with failure of at least four organs (p < 0.001). The area under the
      receiver operating characteristic curve of the total SOFA score for
      discrimination of mortality was 0.68 (95% CI 0.62-0.74). Conclusions: Community
      acquired sepsis in Southeast Asia due to a variety of pathogens is usually
      managed outside the ICU and with poor compliance to sepsis bundles. In this
      population, calculation of SOFA scores is feasible and SOFA scores are associated
      with mortality. Trial registration: ClinicalTrials.gov, NCT02157259. Registered 5
      June 2014, retrospectively registered.

PMID- 29468070
TI  - Reduced alcohol-seeking in male offspring of sires exposed to alcohol self
      administration followed by punishment-imposed abstinence.
AB  - Emerging evidence has demonstrated that paternal alcohol use can modify the
      behavior of offspring, particularly male offspring. However, preclinical studies
      to date have not used voluntary self-administration of alcohol to examine alcohol
      related behaviors in offspring. Here, we tested the hypothesis that paternal
      alcohol self-administration followed by punishment-imposed abstinence alters
      alcohol consumption and seeking in male offspring. Male inbred alcohol preferring
      iP rats were trained to self-administer alcohol in one context followed by
      punishment-imposed suppression of alcohol-seeking in a different context using
      contingent footshock. Following this, all rats were bred with alcohol naive
      female iP rats. F1 offspring were then trained to self-administer alcohol in an
      identical operant paradigm as sires. Alcohol intake and self-administration
      behaviors of alcohol-sired offspring were compared to control-sired offspring
      whose fathers had not been exposed to the alcohol operant conditioning
      experience. We found that paternal alcohol self-administration reduced context
      induced relapse to alcohol-seeking in male offspring. These findings indicate
      that voluntary paternal alcohol experience, operant conditioning, and punishment
      can result in intergenerational changes in offspring behavior, and that this
      effect may protect against the vulnerability to relapse after alcohol use. We
      also noted reduced alcohol responding in the punishment-associated context in
      alcohol-sired offspring, suggesting altered perception of punishment sensitivity
      or the anxiogenic response to footshock. Collectively, these findings provide
      evidence that paternal alcohol abuse can impact alcohol-related behaviors in male
      offspring.

PMID- 29468071
TI  - Dietary tetrahydrocurcumin reduces renal fibrosis and cardiac hypertrophy in 5/6
      nephrectomized rats.
AB  - Tetrahydrocurcumin (THC) is the principal metabolite of curcumin and has
      antioxidant properties. In the present investigation, the effect of THC on renal
      and cardiovascular outcomes was studied in rats with chronic kidney disease
      (CKD). CKD rats were randomized following 5/6 nephrectomy to a special diet for 9
      weeks which contained 1% THC (CKD+THC group). Low-dose
      polyenylphosphatidylcholine was used as a lipid carrier to increase
      bioavailability. Endpoints included tail blood pressure, normalized heart weight,
      plasma and urine biochemical data, and kidney tissue analyses. CKD animals
      demonstrated increased proteinuria, decreased creatinine clearance, hypertension,
      and cardiac hypertrophy. The antioxidant proteins CuZn SOD and glutathione
      peroxidase were decreased in the remnant kidney, while apoptosis (caspase-3) and
      fibrosis (alpha-SM actin) were increased. Renal fibrosis was confirmed
      histologically on trichrome staining. These pathologic changes were ameliorated
      in the CKD+THC group with significant decrease in proteinuria, hypertension, and
      kidney fibrosis. THC therapy restored levels of CuZn SOD and glutathione
      peroxidase. Consistent with prior reports, dietary THC did not improve nuclear
      Nrf2 levels. In summary, dietary THC therapy improved expression of antioxidant
      proteins in the remnant kidney, decreased renal fibrosis and proteinuria, and
      ameliorated hypertension in 5/6 nephrectomized rats.

PMID- 29468072
TI  - Investigation of cardiopulmonary exercise testing using a dynamic leg press and
      comparison with a cycle ergometer.
AB  - Background: Leg-press machines are widely employed for musculoskeletal
      conditioning of the lower-limbs and they provide cardiovascular benefits for
      resistance training in cardiac patients. The aim of this study was to assess the
      feasibility of a dynamic leg press (DLP) for incremental cardiopulmonary exercise
      testing (CPET) and to compare the results with those obtained using a cycle
      ergometer (CE). Methods: Twelve healthy participants aged 27+/-4 years (mean +/-
      standard deviation) performed incremental cardiopulmonary exercise tests on a DLP
      and on a CE. To facilitate CPET, the DLP was augmented with force and angle
      sensors, a work rate estimation algorithm, and a visual feedback system. Gas
      exchange variables and heart rate were recorded breath-by-breath using a
      cardiopulmonary monitoring system. Results: Peak oxygen uptake and peak heart
      rate were significantly lower for the DLP than for the CE: peak oxygen uptake was
      3.2+/-0.5 vs. 4.1+/-0.5 L/min (DLP vs. CE, p=6.7*10-6); peak heart rate was 174+/
      14 vs. 182+/-13 bpm (DLP vs. CE, p=0.0016). Likewise, the sub-maximal
      cardiopulmonary parameters, viz. the first and second ventilatory thresholds, and
      ramp duration were significantly lower for the DLP. Conclusions: The dynamic leg
      press was found to be feasible for CPET: the approach was technically
      implementable and all peak and sub-maximal cardiopulmonary parameters were able
      to be identified. The lower outcome values observed with the DLP can be
      attributed to a peripheral factor, namely the earlier onset of muscular fatigue.

PMID- 29468073
TI  - Survival prediction in mesothelioma using a scalable Lasso regression model:
      instructions for use and initial performance using clinical predictors.
AB  - Introduction: Accurate prognostication is difficult in malignant pleural
      mesothelioma (MPM). We developed a set of robust computational models to quantify
      the prognostic value of routinely available clinical data, which form the basis
      of published MPM prognostic models. Methods: Data regarding 269 patients with MPM
      were allocated to balanced training (n=169) and validation sets (n=100).
      Prognostic signatures (minimal length best performing multivariate trained
      models) were generated by least absolute shrinkage and selection operator
      regression for overall survival (OS), OS <6 months and OS <12 months. OS
      prediction was quantified using Somers DXY statistic, which varies from 0 to 1,
      with increasing concordance between observed and predicted outcomes. 6-month
      survival and 12-month survival were described by area under the curve (AUC)
      scores. Results: Median OS was 270 (IQR 140-450) days. The primary OS model
      assigned high weights to four predictors: age, performance status, white cell
      count and serum albumin, and after cross-validation performed significantly
      better than would be expected by chance (mean DXY0.332 (+/-0.019)). However,
      validation set DXY was only 0.221 (0.0935-0.346), equating to a 22% improvement
      in survival prediction than would be expected by chance. The 6-month and 12-month
      OS signatures included the same four predictors, in addition to epithelioid
      histology plus platelets and epithelioid histology plus C-reactive protein (mean
      AUC 0.758 (+/-0.022) and 0.737 (+/-0.012), respectively). The <6-month OS model
      demonstrated 74% sensitivity and 68% specificity. The <12-month OS model
      demonstrated 63% sensitivity and 79% specificity. Model content and performance
      were generally comparable with previous studies. Conclusions: The prognostic
      value of the basic clinical information contained in these, and previously
      published models, is fundamentally of limited value in accurately predicting MPM
      prognosis. The methods described are suitable for expansion using emerging
      predictors, including tumour genomics and volumetric staging.

PMID- 29468074
TI  - Development of a patient-centred, evidence-based and consensus-based discharge
      care bundle for patients with acute exacerbation of chronic obstructive pulmonary
      disease.
AB  - Introduction: Hospital and emergency department discharge for patients with
      chronic obstructive pulmonary disease (COPD) is often poorly organised. We
      developed a patient-centred, evidence-based and consensus-based discharge care
      bundle for patients with acute exacerbations of COPD. Methods: A purposeful
      sample of clinicians and patients were invited to participate in a two-round
      Delphi study (July-November 2015). In round 1, participants rated on a seven
      point Likert scale (1=not at all important; 7=extremely important) the importance
      of 29 unique COPD care actions. Round 2 comprised items selected from round 1
      based on consensus (>80% endorsement for Likert values 5-7). A list of 18 care
      items from round 2 was discussed in a face-to-face nominal group meeting.
      Results: Seven care items were included in the COPD discharge bundle based on
      clinician and patient input: (1) ensure adequate inhaler technique is
      demonstrated; (2) send discharge summary to family physician and arrange follow
      up; (3) optimise and reconcile prescription of respiratory medications; (4)
      provide a written discharge management plan and assess patient's and caregiver's
      comprehension of discharge instructions; (5) refer to pulmonary rehabilitation;
      (6) screen for frailty and comorbidities; and (7) assess smoking status, provide
      counselling and refer to smoking cessation programme. Conclusion: We present a
      seven-item, patient-centred, evidence-based and consensus-based discharge bundle
      for patients with acute exacerbations of COPD. Alignment with clinical practice
      guidelines and feasibility of local adaptations of the bundle should be explored
      to facilitate wide applicability and evaluation of the effectiveness of the COPD
      discharge bundle.

PMID- 29468075
TI  - Television exposure and overweight/obesity among women in Ghana.
AB  - Background: Although the public health importance of the association between
      television (TV) viewing and obesity and/or related outcomes have been
      demonstrated in both cross-sectional and prospective studies elsewhere, similar
      studies are lacking within the African region. With the view to fill this gap in
      the literature, the current study explored the association between TV exposure
      and overweight/obesity among Ghanaian women. Methods: Based on a sample of 4158
      women, descriptive statistics and binary logistic regression were applied to data
      on TV ownership, TV viewing frequency, and body mass index (BMI) measures from
      the 2014 Ghana Demographic and Health Survey (GDHS) to explore the association
      between TV exposure and overweight/obesity among Ghanaian women. Results: Despite
      controlling for other factors (age educational level, marital status, wealth
      quintile, occupation, type of locality, and parity), the results show that women
      with TV in their households, and with high TV exposure were significantly (P <
      0.05) more likely (OR = 1.39, 95% CI = 1.002, 1.923) to be overweight/obese
      compared to those with no TV in their households, and no TV exposure. Conclusion:
      The study demonstrates that increased TV exposure is significantly associated
      with overweight/obesity among women in Ghana even after adjusting for other
      factors. Interventions aimed at tackling obesity in Ghana should focus on
      encouraging the uptake of more physically demanding pastime activities in place
      of TV "sit time".

PMID- 29468076
TI  - Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of
      appetite in dogs.
AB  - Ghrelin is a hormone, secreted from cells in the stomach, which is important in
      the regulation of appetite and food intake in mammals. It exerts its action by
      binding to a specific G-protein-coupled receptor, the growth hormone secretagogue
      receptor 1a (GHS-R1a) which is found in areas of the brain associated with the
      regulation of food intake. Ghrelin causes a release of growth hormone (GH)
      through binding to GHS-R1a in the hypothalamus and pituitary gland. A class of
      compounds known as growth hormone secretagogues, or ghrelin receptor agonists,
      were developed for therapeutic use in humans for the stimulation of GH in the
      frail elderly, and have subsequently been studied for their effects on increasing
      appetite and food intake, increasing body weight, building lean muscle mass, and
      treating cachexia. Subsequent research has shown that ghrelin has anti
      inflammatory and immunomodulatory effects. This article reviews the basic
      physiology of ghrelin and the ghrelin receptor agonists, including the available
      evidence of these effects in vitro and in vivo in rodent models, humans, dogs and
      cats. One of these compounds, capromorelin, has been FDA-approved for the
      stimulation of appetite in dogs (ENTYCE (r)). The data available on the safety
      and effectiveness of capromorelin is reviewed, along with a discussion of the
      potential clinical applications for ghrelin receptor agonists in both human and
      veterinary medicine.

PMID- 29468077
TI  - Molecular prevalence and phylogenetic analysis of Theileria annulata and
      Trypanosoma evansi in cattle in Northern Tunisia.
AB  - The present study aimed to estimate the molecular prevalence of Theileria
      annulata and Trypanosoma evansi infection in cattle in Northern Tunisia. A total
      number of 96 cattle from five farms were evaluated. T. annulata and T. evansi
      prevalences were 61% [56/66] and 10% [7/13], respectively, at a confidence
      interval (CI) of 95%, while co-infection was present in 6% [4/8] of the tested
      animals at a CI of 95%. There was a significant correlation between age and the
      prevalence of T. annulata infection, whereas, there was no significant
      association shown with the age of cattle and T. evansi infection. Sequence and
      phylogenetic analyses showed that the T. annulata Tams1 gene and T. evansi ITS1
      rDNA gene were highly conserved with 97.1-100% and 98.3-100% sequence identity,
      respectively.

PMID- 29468078
TI  - Serovars and antimicrobial resistance of non-typhoidal Salmonella isolated from
      non-diarrhoeic dogs in Grenada, West Indies.
AB  - Non-typhoidal salmonellosis remains an important public health problem worldwide.
      Dogs may harbour Salmonella in their intestines and can easily shed Salmonella in
      the environment with the possibility of transmission to humans. Thus, monitoring
      is essential to understand the role of dogs in zoonotic transmission. The
      objectives of this study were to determine the shedding of Salmonella by owned,
      apparently healthy dogs in Grenada, West Indies, to identify the serovars, and to
      examine their antimicrobial susceptibility profiles. Faecal samples collected
      during August to October, 2016 from 144 non-diarrhoeic owned dogs were examined
      by enrichment and selective culture for the presence of Salmonella spp. Eight
      (5.6%) of the tested animals were culture positive, yielding 35 Salmonella
      isolates that belonged to six serovars of Salmonella enterica subspecies
      enterica. These were serovars Arechavaleta from two dogs, Arechavaleta and
      Montevideo from one dog, and Javiana, Rubislaw, Braenderup and Kiambu from one
      dog each. All these serovars have been reported as causes of human salmonellosis
      globally. Antimicrobial susceptibility tests on 35 isolates showed absence of
      resistance to the currently used drugs for cases of human salmonellosis,
      including ciprofloxacin and cefotaxime. One isolate (2.9%) was resistant to
      neomycin, two isolates (5.7%) showed intermediate susceptibility to neomycin, and
      another (2.9%) had intermediate susceptibility to tetracycline. This is the first
      report of isolation and antimicrobial susceptibilities of non-typhoidal
      Salmonella serovars from dogs in Grenada. This study shows that dogs in Grenada
      may be involved in the epidemiology of salmonellosis.

PMID- 29468079
TI  - Effect of vaccine storage temperatures and dose rate on antibody responses to
      foot and mouth disease vaccination in Cambodia.
AB  - A field study investigated the effects of foot and mouth disease vaccine storage
      temperature for 7 days (frozen, refrigerated or held at ambient temperature) and
      dose (half or full dose) on the serological response to vaccination. It utilised
      a complete factorial design replicated on 18 smallholder cattle farms in three
      villages in Pursat province, Cambodia. Antibody responses from the 108 cattle
      involved were assessed by serological examination of blood samples collected at
      primary vaccination (day 0), at booster vaccination (day 30) and finally at 60
      days post primary vaccination. Vaccination responses to the inactivated vaccine
      were assessed by testing for antibodies directed against FMD structural proteins
      in a liquid-phase blocking ELISA (LPBE test) and differentiated from responses to
      natural infection by examining antibody titres against non-structural viral
      proteins (NSPE test). LPBE results indicated that the mean log10 LPBE antibody
      titres of all experimental cattle increased from below protective levels at day 0
      to protective levels at 30 days post primary vaccination, and increased further
      at 60 days post primary vaccination. Storage at ambient temperature for 1 week
      had no effect on antibody response to vaccination. However, freezing the vaccine
      for a week or use of a half dose resulted in significant reduction in titres at
      day 60 (P = 0.04 and P = 0.02, respectively). The results of this study reinforce
      the need to store FMD vaccines within the range recommended by the manufacturers
      and to adhere to the specified dosage instructions.

PMID- 29468080
TI  - An outbreak of classical swine fever in pigs in Bangladesh, 2015.
AB  - In a group of 22 healthy pigs aged between 4 and 6 months, 2 pigs became ill with
      high fever, complete anorexia, cough and abnormal swaying movements on 22 June
      2015. One of them died on June 24 and the second died on July 3. Shortly after,
      the remaining pigs also fell ill and died from the same illness by 10 August
      2015. We investigated the aetiology, epidemiological and clinical features of the
      outbreak. We recorded the clinical signs and symptoms for each pig with the date
      of onset of illness. Veterinarians conducted post-mortem examinations on the 12
      dead pigs, they collected tissue samples from the dead pigs and placed them in a
      tube containing 1 mL of nucleic acid extraction buffer (lysis buffer). We tested
      all the tissue samples by real-time reverse transcription polymerase chain
      reaction (rRT-PCR) to detect classical swine fever virus (CSFV) because the
      animals' symptoms matched those of this disease. We also conducted a phylogentic
      analysis of the nucleotide sequence of the E2 gene segment of CSFV detected in a
      lung tissue sample. The attack rate (22/22) and the case fatality were 100%. The
      predominant symptoms of the disease included high fever, cough, diarrhoea and
      swaying movements of the hind legs prior to death. Of the 12 pigs tissue samples
      tested, all had evidence of the presence of CSFV RNA by rRT-PCR. The phylogenetic
      analysis indicated that the virus belongs to genotype 2.2, which is closely
      related to CSFV genotype 2.2 reported in India. Our investigation suggests that
      CSF is circulating in pigs, posing a risk for communities in Bangladesh that rely
      on pigs for economic income and dietary protein. Future research could focus on
      estimating the disease and economic burden of CSFV in pig rearing areas to
      determine if interventions might be warranted or cost-effective.

PMID- 29468081
TI  - Progressive cutaneous viral pigmented plaques in three Hungarian Vizslas and the
      response of lesions to topical tigilanol tiglate gel.
AB  - Cutaneous pigmented viral plaques is a disorder of epidermal growth caused by
      canine papillomavirus type 4 (CPV-4). There is currently no standard of care for
      managing this condition and it has not been reported in the Hungarian Vizsla.
      This case series documents the clinical features of canine pigmented viral
      plaques in Hungarian Vizsla dogs and the treatment of a severe case using a novel
      topical agent tigilanol tiglate (EBC-46). A 4-year-old spayed Hungarian Vizsla in
      Australia was presented for multiple cutaneous pigmented plaques extending from
      the ventral cervical region. Lesions were neither painful nor pruritic. The
      number and size of these sessile plaques increased over time, with the largest
      lesions eventually taking on an exophytic (wart-like) appearance. These lesions
      did not affect the dog's wellbeing. Two much less severe cases in a 5-year-old
      Vizsla from the UK and a 7-year-old Vizsla from New Zealand were also diagnosed.
      Histology was consistent with papillomavirus-induced pigmented plaques and CPV-4
      DNA sequences were amplified from paraffin-embedded formalin-fixed tissue using
      the polymerase chain reaction from the most severely affected patient. Topical
      imiquimod was ineffective although used for only a short time. Two topical
      applications of novel anti-neoplastic diterpene ester tigilanol tiglate as a gel,
      9 days apart, greatly reduced the size and number of lesions in a limited portion
      of skin treated, over the lateral hock. While CPV-4 has been previously reported
      to cause pigmented plaques, most commonly on pug dogs, but sporadically on other
      breeds, this is the first report of this virus causing plaques in Hungarian
      Vizslas. The cases illustrate some of the difficulties in diagnosing
      papillomavirus-induced disease in dogs, especially in its early stages. Topical
      tigilanol tiglate is a potentially useful topical therapy for this viral-induced
      disorder of cell growth and represents a treatment deserving of further
      investigation.

PMID- 29468082
TI  - Concurrent thoracic mesothelioma and thyroid C-cell adenoma with amyloid
      deposition in an aged horse.
AB  - A 21-year-old American Saddlebred mare died with a history of weight loss and
      breathing difficulties of 1 month duration. Post-mortem examination revealed a
      copious pleural effusion with multifocal to coalescing numerous white to grey
      nodular masses on the serosal surface of the pericardium, lungs and thoracic
      cavity. In addition, the left thyroid gland was markedly enlarged. A thoracic
      mesothelioma and C-cell adenoma with amyloid deposits of the left thyroid gland
      were diagnosed by histopathology and confirmed by immunohistochemistry employing
      antibodies against cytokeratin (CK), vimentin and calcitonin. Amyloid deposits in
      the thyroid tumour were confirmed by Congo red staining with apple-green
      birefringence under polarized light. Mesothelioma remains an uncommon neoplasm
      encountered in aged horses. Discussion includes the diagnostic challenge of
      differentiating carcinomatosis from mesothelioma by histology and differentiating
      reactive and neoplastic mesothelial cells by cytology.

PMID- 29468083
TI  - Research note: a resting-state, cerebello-amygdaloid intrinsically connected
      network.
AB  - Background: Previous ROI-based functional connectivity studies found functional
      coherence between cerebellum and cerebral amygdale, at rest. Moreover, some
      neurospychiatric symptoms were accompanied by abnormal activations of these two
      brain areas. Therefore, the aim of the study was to identify a putative, resting
      state intrinsically connected cerebello-amygdaloid network. Methods: ICA-based
      analysis was performed on brain resting-state functional images of 15 volunteers.
      Results: The first ICA spatial component corresponded to a circuit including:
      dentate nuclei, lobules VI and VIII, the basolateral amygdala, the substantia
      nigra, the posterior insula, claustrum and the parietal opercule. Conclusion: A
      new intrinsically connected network linking cerebellum and amygdala is described,
      which could be in charge of sensorimotor, emotional and motivational integration
      of somesthesic stimuli before recruiting more specialized circuits such as
      ventral striatum or attentional and salience networks.

PMID- 29468085
TI  - Feasibility of a combined aerobic and cognitive training intervention on
      cognitive function in cancer survivors: a pilot investigation.
AB  - Background: Cancer-related cognitive impairment (CRCI) may negatively affect
      upwards of 75% of cancer patients. Exercise and cognitive training,
      independently, may increase functional capacity and aspects of cognitive
      function. Yet, combined training protocols have not been evaluated in cancer
      survivor populations. Therefore, the aim of this study was to explore the
      feasibility of a quasi-randomized, controlled, exploratory, repeated-measures
      aerobic and cognitive training intervention on cognitive function in participants
      undergoing treatment for cancer (N = 28). Methods: Pre- and post-physical and
      cognitive assessments were administered. A 36-session (approximately 12 weeks)
      computer-based cognitive (COG), aerobic (AER), cognitive and aerobic (AER + COG),
      and flexibility (CON) training intervention was completed. Dependent measures t
      tests and pre- to post percentages were then calculated to address within-group
      changes for each dependent variable. Results: Within-group measures revealed that
      the AER logical memory scores (pre- to post mean difference [2.3], 95.0% CI [0.9,
      3.7], percentage change [32.7%]), delayed recall scores (pre- to post mean
      difference [2.1], 95.0% CI [0.3, 3.9], percentage change [27.2%]), block design
      scores (pre- to post mean difference [1.7], 95.0% CI [0.2, 3.2], percentage
      change [19.0%]), and letter-number sequencing scores (pre- to post mean
      difference [1.0], 95.0% CI [0.2, 1.8], percentage change [12.3%]) all increased.
      Aspects of verbal fluidity scores increased in the CON group. However, all
      cognitive scores (AER + COG and COG groups) failed to increase. Conclusions:
      Aerobic training for CRCI may positively impact cognitive function. Individually,
      these methods may appropriately address CRCI, but combined training of this
      nature may be too demanding for patients undergoing treatment for cancer.
      However, larger randomized trials are needed to substantiate this protocol in
      large-scale cancer rehabilitation centers.

PMID- 29468084
TI  - A development study and randomised feasibility trial of a tailored intervention
      to improve activity and reduce falls in older adults with mild cognitive
      impairment and mild dementia.
AB  - Background: People with dementia progressively lose abilities and are prone to
      falling. Exercise- and activity-based interventions hold the prospect of
      increasing abilities, reducing falls, and slowing decline in cognition. Current
      falls prevention approaches are poorly suited to people with dementia, however,
      and are of uncertain effectiveness. We used multiple sources, and a co-production
      approach, to develop a new intervention, which we will evaluate in a feasibility
      randomised controlled trial (RCT), with embedded adherence, process and economic
      analyses. Methods: We will recruit people with mild cognitive impairment or mild
      dementia from memory assessment clinics, and a family member or carer. We will
      randomise participants between a therapy programme with high intensity
      supervision over 12 months, a therapy programme with moderate intensity
      supervision over 3 months, and brief falls assessment and advice as a control
      intervention. The therapy programmes will be delivered at home by mental health
      specialist therapists and therapy assistants. We will measure activities of daily
      living, falls and a battery of intermediate and distal health status outcomes,
      including activity, balance, cognition, mood and quality of life. The main aim is
      to test recruitment and retention, intervention delivery, data collection and
      other trial processes in advance of a planned definitive RCT. We will also study
      motivation and adherence, and conduct a process evaluation to help understand why
      results occurred using mixed methods, including a qualitative interview study and
      scales measuring psychological, motivation and communication variables. We will
      undertake an economic study, including modelling of future impact and cost to end
      of-life, and a social return on investment analysis. Discussion: In this study,
      we aim to better understand the practicalities of both intervention and research
      delivery, and to generate substantial new knowledge on motivation, adherence and
      the approach to economic analysis. This will enable us to refine a novel
      intervention to promote activity and safety after a diagnosis of dementia, which
      will be evaluated in a definitive randomised controlled trial. Trial
      registration: ClinicalTrials.gov: NCT02874300; ISRCTN 10550694.

PMID- 29468086
TI  - DNA metabarcoding of spiders, insects, and springtails for exploring potential
      linkage between above- and below-ground food webs.
AB  - Background: Understanding feedback between above- and below-ground processes of
      biological communities is a key to the effective management of natural and
      agricultural ecosystems. However, as above- and below-ground food webs are often
      studied separately, our knowledge of material flow and community dynamics in
      terrestrial ecosystems remains limited. Results: We developed a high-throughput
      sequencing method for examining how spiders link above- and below-ground food
      webs as generalist predators. To overcome problems related to DNA-barcoding-based
      analyses of arthropod-arthropod interactions, we designed spider-specific
      blocking primers and Hexapoda-specific primers for the selective PCR
      amplification of Hexapoda prey sequences from spider samples. By applying the new
      DNA metabarcoding framework to spider samples collected in a temperate secondary
      forest in Japan, we explored the structure of a food web involving 15 spider
      species and various taxonomic groups of Hexapoda prey. These results support the
      hypothesis that multiple spider species in a community can prey on both above-
      and below-ground prey species, potentially coupling above- and below-ground food
      web dynamics. Conclusions: The PCR primers and metabarcoding pipeline described
      in this study are expected to accelerate nuclear marker-based analyses of food
      webs, illuminating poorly understood trophic interactions in ecosystems.

PMID- 29468087
TI  - Development of hypobranchial muscles with special reference to the evolution of
      the vertebrate neck.
AB  - Background: The extant vertebrates include cyclostomes (lamprey and hagfish) and
      crown gnathostomes (jawed vertebrates), but there are various anatomical
      disparities between these two groups. Conspicuous in the gnathostomes is the
      neck, which occupies the interfacial domain between the head and trunk, including
      the occipital part of the cranium, the shoulder girdle, and the cucullaris and
      hypobranchial muscles (HBMs). Of these, HBMs originate from occipital somites to
      form the ventral pharyngeal and neck musculature in gnathostomes. Cyclostomes
      also have HBMs on the ventral pharynx, but lack the other neck elements,
      including the occipital region, the pectoral girdle, and cucullaris muscles.
      These anatomical differences raise questions about the evolution of the neck in
      vertebrates. Results: In this study, we observed developing HBMs as a basis for
      comparison between the two groups and show that the arrangement of the head-trunk
      interface in gnathostomes is distinct from that of lampreys. Our comparative
      analyses reveal that, although HBM precursors initially pass through the lateral
      side of the pericardium in both groups, the relative positions of the pericardium
      withrespect to the pharyngeal arches differ between the two, resulting in diverse
      trajectories of HBMs in gnathostomes and lampreys. Conclusions: We suggest that a
      heterotopic rearrangement of early embryonic components, including the
      pericardium and pharyngeal arches, may have played a fundamental role in
      establishing the gnathostome HBMs, which would also have served as the basis for
      neck formation in the jawed vertebrate lineage.

PMID- 29468088
TI  - Neck circumference is independently associated with relative systemic
      hypertension in young adults with sickle cell anaemia.
AB  - Background: A seemingly interesting observation in patients with sickle cell
      anaemia (SCA) is that they usually have lower systemic blood pressures (BP) and
      insulin resistance than persons in the general population in spite of chronic
      inflammation and vasculopathy. However, relative systemic hypertension (rHTN) has
      been linked to pulmonary hypertension, increased blood viscosity and renal
      insufficiency, which could indicate a risk of developing cardiometabolic disorder
      (CMD) in SCA.We therefore hypothesized that neck circumference (NC) and CMD
      marker; triglyceride glucose (TyG) index would independently predict rHTN in
      young adults with SCA in steady state. Methods: We compared the anthropometrical,
      hematological, hemorheological and CMD markers between SCA patients with normal
      BP < 120/70 mmHg; nHTN, n = 65) and those with rHTN (BP >= 120/70 mmHg, n = 32).
      Results: Our results showed that SCA with rHTN had significantly higher body
      weight, waist circumference, NC, plasma viscosity, systolic and diastolic BP.
      Results also indicated that NC (OR: 2.98; 95% CI 1.46 to 6.10, p < 0.01) was a
      predictor of rHTN in SCA independent of gender, age, weight, waist circumference,
      BMI, blood viscosity, triglyceride or TyG. A receiver operating characteristic
      curve analysis also showed that NC was the most efficient predictor of rHTN than
      other CMD markers. Conclusion: The present study demonstrates that increased NC
      is a salient risk factors that is independently associated with rHTN in SCA. The
      finding therefore underscores the utility of NC in early detection and
      stratification of systemic hypertension, particularly in individuals with SCA.

PMID- 29468089
TI  - The necessary conditions of engagement for the therapeutic relationship in
      physiotherapy: an interpretive description study.
AB  - Background: The therapeutic relationship between patient and physiotherapist is a
      central component of patient-centred care and has been positively associated with
      better physiotherapy clinical outcomes. Despite its influence, we do not know
      what conditions enable a physiotherapist and patient to establish and maintain a
      therapeutic relationship. This knowledge has implications for how clinicians
      approach their interactions with patients and for the development of an
      assessment tool that accurately reflects the nature of the therapeutic
      relationship. Therefore, this study's aim was to identify and provide in-depth
      descriptions of the necessary conditions of engagement of the therapeutic
      relationship between physiotherapists and patients. Methods: Interpretive
      description was the qualitative methodological orientation used to identify and
      describe the conditions that reflect and are practically relevant to clinical
      practice. Eleven physiotherapists with a minimum 5 years of clinical experience
      and seven adult patients with musculoskeletal disorders were purposively sampled
      from private practice clinics in Edmonton, Canada. The in-person, semi-structured
      interviews were completed in a location of the participant's choice and were
      audio recorded and transcribed. Qualitative content analysis was used to analyze
      the textual data and constant comparison techniques were integrated to refine the
      categories and sub-categories. Rigour strategies used throughout the study were
      peer debrief, interview notes, reflexive journaling, memoing, member reflections,
      audit trail, and external audit. Results: Four conditions were identified as
      necessary for establishing a therapeutic relationship: present, receptive,
      genuine, and committed. These conditions represent the intentions and attitudes
      of physiotherapists and patients engaging in the clinical interaction. Although
      distinct, the conditions appear related as being present and receptive create a
      foundation for being genuine and committed. Conclusions: These conditions of
      engagement are needed for physiotherapist and patient to "be" in a therapeutic
      relationship. Although communication skills are important for advancing
      therapists' relational abilities, awareness and integration of intentions and
      attitudes are essential for shaping behaviors that develop the therapeutic
      relationship. These findings also suggest there are characteristics of the
      therapeutic relationship specific to physiotherapy. Therefore, theories from
      other contexts (e.g., psychotherapy) should be used judiciously to guide
      physiotherapy practice and research.

PMID- 29468090
TI  - The Role of BMI in Hip Fracture Surgery.
AB  - Introduction: Obesity is an oft-cited cause of surgical morbidity and many
      institutions require extensive supplementary screening for obese patients prior
      to surgical intervention. However, in the elderly patients, obesity has been
      described as a protective factor. This article set out to examine the effect of
      body mass index (BMI) on outcomes and morbidity after hip fracture surgery.
      Methods: The National Surgical Quality Improvement Program database was queried
      for all patients undergoing 1 of 4 surgical procedures to manage hip fracture
      between 2008 and 2012. Patient demographics, BMI, and known factors that lead to
      poor surgical outcomes were included as putative predictors for complications
      that included infectious, cardiac, pulmonary, renal, and neurovascular events.
      Using chi2 tests, 30-day postoperative complication rates were compared between 4
      patient groups stratified by BMI as low weight (BMI < 20), normal (BMI = 20-30),
      obese (BMI = 30-40), and morbidly obese (BMI > 40). Results: A total of 15 108
      patients underwent surgery for hip fracture over the examined 5-year period. Of
      these, 18% were low weight (BMI < 20), 67% were normal weight (BMI = 20-30), 13%
      were obese (BMI = 30-40), and 2% were morbidly obese (BMI > 40). The low-weight
      and morbidly obese patients had both the highest mortality rates and the lowest
      superficial infection rates. There was a significant increase in blood
      transfusion rates that decreased linearly with increasing BMI. Deep surgical site
      infection and renal failure increased linearly with increasing BMI, however,
      these outcomes were confounded by comorbidities. Conclusion: This study
      demonstrates that patients at either extreme of the BMI spectrum, rather than
      solely the obese, are at greatest risk of major adverse events following hip
      fracture surgery. This runs contrary to the notion that obese hip fracture
      patients automatically require additional preoperative screening and
      perioperative services, as currently implemented in many institutions.

PMID- 29468092
TI  - Effectiveness of Culturally Appropriate Adaptations to Juvenile Justice Services.
AB  - Despite efforts to increase cultural competence of services within juvenile
      justice systems, disproportional minority contact (DMC) persists throughout
      Canada and the United States. Commonly cited approaches to decreasing DMC include
      large-scale systemic changes as well as enhancement of the cultural relevance and
      responsiveness of services delivered. Cultural adaptations to service delivery
      focus on prevention, decision-making, and treatment services to reduce initial
      contact, minimize unnecessary restraint, and reduce recidivism. Though locating
      rigorous testing of these approaches compared to standard interventions is
      difficult, this paper identifies and reports on such research. The Cochrane
      guidelines for systematic literature reviews and meta-analyses served as a
      foundation for study methodology. Databases such as Legal Periodicals and Books
      were searched through June 2015. Three studies were sufficiently rigorous to
      identify the effect of the cultural adaptations, and three studies that are
      making potentially important contributions to the field were also reviewed.

PMID- 29468093
TI  - Integration of Health Coaching Concepts and Skills into Clinical Practice Among
      VHA Providers: A Qualitative Study.
AB  - Background: Although studies of health coaching for behavior change in chronic
      disease prevention and management are increasing, to date no studies have
      reported on what concepts and skills providers integrate into their clinical
      practice following participation in health coaching courses. The purpose of this
      qualitative study was to assess Veterans Health Administration (VHA) providers'
      perceptions of the individual-level and system-level changes they observed after
      participating with colleagues in a 6-day Whole Health Coaching course held in 8
      VHA medical centers nationwide. Methods: Data for this study were from the follow
      up survey conducted with participants 2 to 3 months after completing the
      training. A total of 142 responses about individual-level changes and 99
      responses about system-level changes were analyzed using content analysis.
      Results: Eight primary themes emerged regarding individual changes, including
      increased emphasis on Veterans' values, increased use of listening and other
      specific health coaching skills in their clinical role, and adding health
      coaching to their clinical practice.Four primary themes emerged regarding system
      level changes, including leadership support, increased staff
      awareness/support/learning and sharing, increased use of health coaching skills
      or tools within the facility, and organizational changes demonstrating a more
      engaged workforce, such as new work groups being formed or existing groups
      becoming more active. Conclusions: Findings suggest that VHA providers who
      participate in health coaching trainings do perceive positive changes within
      themselves and their organizations. Health coaching courses that emphasize
      patient-centered care and promote patient-provider partnerships likely have
      positive effects beyond the individual participants that can be used to promote
      desired organizational change.

PMID- 29468091
TI  - Surgical Technical Evidence Review for Elective Total Joint Replacement Conducted
      for the AHRQ Safety Program for Improving Surgical Care and Recovery.
AB  - Background: Use of enhanced recovery pathways (ERPs) can improve patient
      outcomes, yet national implementation of these pathways remains low. The Agency
      for Healthcare Research and Quality (AHRQ; funder), the American College of
      Surgeons, and the Johns Hopkins Medicine Armstrong Institute for Patent Safety
      and Quality have developed the Safety Program for Improving Surgical Care and
      Recovery-a national effort to catalyze implementation of practices to improve
      perioperative care and enhance recovery of surgical patients. This review
      synthesizes evidence that can be used to develop a protocol for elective total
      knee arthroplasty (TKA) and total hip arthroplasty (THA). Study Design: This
      review focuses on potential components of the protocol relevant to surgeons;
      anesthesia components are reported separately. Components were identified through
      review of existing pathways and from consultation with technical experts. For
      each, a structured review of MEDLINE identified systematic reviews, randomized
      trials, and observational studies that reported on these components in patients
      undergoing elective TKA/THA. This primary evidence review was combined with
      existing clinical guidelines in a narrative format. Results: Sixteen components
      were reviewed. Of the 10 preoperative components, most were focused on risk
      factor assessment including anemia, diabetes mellitus, tobacco use, obesity,
      nutrition, immune-modulating therapy, and opiates. Preoperative education, venous
      thromboembolism (VTE) prophylaxis, and bathing/Staphylococcus aureus
      decolonization were also included. The routine use of drains was the only
      intraoperative component evaluated. The 5 postoperative components included early
      mobilization, continuous passive motion, extended duration VTE prophylaxis, early
      oral alimentation, and discharge planning. Conclusion: This review synthesizes
      the evidence supporting potential surgical components of an ERP for elective
      TKA/THA. The AHRQ Safety Program for Improving Surgical Care and Recovery aims to
      guide hospitals and surgeons in identifying the best practices to implement in
      the surgical care of TKA and THA patients.

PMID- 29468094
TI  - CHOBS: Color Histogram of Block Statistics for Automatic Bleeding Detection in
      Wireless Capsule Endoscopy Video.
AB  - Wireless capsule endoscopy (WCE) is the most advanced technology to visualize
      whole gastrointestinal (GI) tract in a non-invasive way. But the major
      disadvantage here, it takes long reviewing time, which is very laborious as
      continuous manual intervention is necessary. In order to reduce the burden of the
      clinician, in this paper, an automatic bleeding detection method for WCE video is
      proposed based on the color histogram of block statistics, namely CHOBS. A single
      pixel in WCE image may be distorted due to the capsule motion in the GI tract.
      Instead of considering individual pixel values, a block surrounding to that
      individual pixel is chosen for extracting local statistical features. By
      combining local block features of three different color planes of RGB color
      space, an index value is defined. A color histogram, which is extracted from
      those index values, provides distinguishable color texture feature. A feature
      reduction technique utilizing color histogram pattern and principal component
      analysis is proposed, which can drastically reduce the feature dimension. For
      bleeding zone detection, blocks are classified using extracted local features
      that do not incorporate any computational burden for feature extraction. From
      extensive experimentation on several WCE videos and 2300 images, which are
      collected from a publicly available database, a very satisfactory bleeding frame
      and zone detection performance is achieved in comparison to that obtained by some
      of the existing methods. In the case of bleeding frame detection, the accuracy,
      sensitivity, and specificity obtained from proposed method are 97.85%, 99.47%,
      and 99.15%, respectively, and in the case of bleeding zone detection, 95.75% of
      precision is achieved. The proposed method offers not only low feature dimension
      but also highly satisfactory bleeding detection performance, which even can
      effectively detect bleeding frame and zone in a continuous WCE video data.

PMID- 29468095
TI  - Intraoral Dissection of the Mimetic Muscles: Application to Dentistry and Oral
      Surgery.
AB  - Mimetic muscles contract and pull the overlying skin toward the muscle's bony
      attachment. Numerous books and articles have shown the mimetic muscles via
      cadaveric dissection. However, for dentistry and oral surgery, the mimetic
      muscles have not been detailed from intraoral dissection. Recently, several
      papers have addressed various mimetic muscles in relation to intraoral
      dissection. However, to our knowledge, there has been no overview of these
      muscles beneath the oral mucosa. Here, we review the literature concerning the
      mimetic muscles as revealed during intraoral dissection, create novel
      illustrations, and discuss the relationship of these muscles with general
      dentistry and oral surgery. The mimetic muscles, which constitute the surface of
      the oral mucosa, the relationship of the labial and buccal frenulum and mimetic
      muscles, the relationship of the mucogingival junction and mimetic muscles, and
      other surgical procedures are discussed. A better understanding of the mimetic
      muscles from an intraoral perspective is important for those performing oral
      surgery and dentistry.

PMID- 29468096
TI  - Omental Infarction: The Great Impersonator.
AB  - A 58-year-old female presented to the emergency department with intermittent
      right upper quadrant pain and nausea. On examination, the patient was tender and
      Murphy's sign was elicited. A presumptive diagnosis of acute cholecystitis was
      made but an ultrasound of the abdomen revealed a thin-walled gallbladder without
      calculi. A computed tomography (CT) scan of the abdomen and pelvis demonstrated
      fat stranding involving the greater omentum and the right paracolic gutter. The
      patient was diagnosed with a focal omental infarction and underwent emergency
      laparoscopic surgery. Intraoperatively, the thickened and infarcted omental
      segment was dissected off the abdominal wall, liver, and mesocolon and removed
      through the umbilical port site using an Endo CatchTM (Covidien Ltd, Dublin,
      Republic of Ireland). This paper presents a rare case of omental infarction and
      illustrates how it can mimic the classic presentation of acute cholecystitis. The
      literature around the incidence, pathogenesis, and management of omental
      infarction is reviewed and presented to the reader.

PMID- 29468097
TI  - An Uncommon Case of Renal Metastasis from Cervical Cancer.
AB  - Metastases to the kidney are a rare entity. Among solid tumors, it is known that
      lung and colorectal cancers can metastasize to the kidney. Renal metastases from
      cervical cancer are exceptional; only 12 cases were previously reported. We
      report a case of a right renal metastasis from a cervical squamous cell
      carcinoma, occurring in the context of a metastatic relapse two years after
      completing primary treatment.

PMID- 29468098
TI  - Dengue Maculopathy with Foveolitis in a Postpartum Female.
AB  - Dengue fever is common in the tropics and its clinical manifestations and
      complications are well-known. However, dengue-related ocular complications are
      rare. Here we present a postpartum female who complained of bilateral central
      scotoma, at five days after the clinical diagnosis of dengue fever. The ocular
      examination was suggestive of dengue maculopathy and foveolitis. She was treated
      with a combination of intravenous methylprednisolone and immunoglobulin. The
      final visual recovery was good.

PMID- 29468099
TI  - Effect of Gamma Knife Radiosurgery and Programmed Cell Death 1 Receptor
      Antagonists on Metastatic Melanoma.
AB  - Learning objectives To evaluate radiation-induced changes in patients with brain
      metastasis secondary to malignant melanoma who received treatment with Gamma
      Knife radiosurgery (GKRS) and programmed cell death 1 (PD-1) receptor
      antagonists. Introduction  Stereotactic radiosurgery and chemotherapeutics are
      used together for treatment of metastatic melanoma and have been linked to
      delayed radiation-induced vasculitic leukoencephalopathy (DRIVL). There have been
      reports of more intense interactions with new immunotherapeutics targeting PD-1
      receptors, but their interactions have not been well described and may result in
      an accelerated response to GKRS. Here we present data on subjects treated with
      this combination from a single institution. Methods Records from patients who
      underwent treatment for metastatic melanoma to the brain with GKRS from 2011 to
      2016 were reviewed. Demographics, date of brain metastasis diagnosis, cause of
      death when applicable, immunotherapeutics, and imaging findings were recorded.
      The timing of radiation therapy and medications were also documented.  Results A
      total of 79 subjects were treated with GKRS, and 66 underwent treatment with both
      GKRS and immunotherapy. Regarding the 30 patients treated with anti-PD-1
      immunotherapy, 21 patients received pembrolizumab, seven patients received
      nivolumab, and two patients received pembrolizumab and nivolumab. Serial imaging
      was available for interpretation in 25 patients, with 13 subjects who received
      GKRS and anti-PD-1 immunotherapy less than six weeks of each other. While four
      subjects had indeterminate/mixed findings on subsequent magnetic resonance
      imaging (MRI), nine subjects were noted to have progression. Two of these
      patients showed progression but subsequent imaging revealed a decrease in
      progression or improvement on MRI to previously targeted lesions by GKRS. None of
      the 13 subjects had surgery following their combined therapies. Conclusions This
      data suggests that there is need for further investigation of the role for
      concurrent treatment with PD-1 inhibitors and GKRS to enhance the treatment of
      metastatic melanoma. We present data on 13 patients who appear to have some
      radiologic benefit to this treatment combination, two of whom had radiographic
      pseudoprogression.

PMID- 29468100
TI  - Bursal Synovial Chondromatosis Secondary to Underlying Osteochondroma in a Child.
AB  - Osteochondroma and synovial chondromatosis are frequently reported benign bony
      and cartilaginous lesions. Osteochondroma is distinguished by a cartilage-capped
      bony exostosis on the exterior surface of the bone, whereas synovial
      chondromatosis is secondary to metaplasia and is characterized by multiple
      cartilaginous loose bodies within the synovium. We present an atypical case of
      synovial chondromatosis developing in a bursa sec-ondary to an underlying
      osteochondroma of the proximal medial tibia in a child. It is extremely rare to
      see both these conditions occurring in one location simultaneously. Moreover,
      this association is an unusual occurrence in the pediatric age group. The patient
      underwent surgical excision of the lesions and the final diagnosis was confirmed
      on histology. Simulation to malignant degeneration is often observed and vigilant
      assessment of both lesions is essential to exclude the possibility of sarcomatous
      transformation in those who present with these conditions since clinical,
      radiological, and histopathological features may overlap. However, a proper
      preoperative distinction may prevent an unnecessary aggressive therapeutic
      approach, which stood true for our case.

PMID- 29468101
TI  - Idiopathic Sudden Sensorineural Hearing Loss: Average Time Elapsed Before
      Presentation to the Otolaryngologist and Effectiveness of Oral and/or
      Intratympanic Steroids in Late Presentations.
AB  - Objectives To determine how long after symptom onset that the average patient
      with an idiopathic sudden sensorineural hearing loss (ISSNHL) presents to the
      otolaryngology clinic.  In late presentations, to determine the time to
      presentation cutoff after which intervention may not be effective.  To evaluate
      the effectiveness of oral steroids versus a combination of oral and intratympanic
      steroid therapy in late presentations of ISSNHL.  Methods and procedures Sixty
      four patients met inclusion criteria after chart review of 2,037 patients seen at
      Metro Health Hospital from 2006 to 2016 for sensorineural hearing loss. All sixty
      four patients were used to calculate the average time to presentation, but only
      40 were included to evaluate treatment efficacy because 24 were lost to follow-up
      or declined treatment. Audiograms were analyzed for baseline status and response
      to treatment. Therapy was either oral steroids or intratympanic (IT) steroids.
      Thirty-nine of the 40 treated patients received oral steroid therapy. Eighteen of
      these 39 patients received both oral and IT steroids. One patient received IT
      steroids only.  Results For all 64 patients in the study, the average time to
      presentation was 55 days, ranging from one day to 240 days. Data for 32 of the 40
      treated patients were analyzed. These patients were further divided into smaller
      groups: Group 1 (N = 11) - treatment within seven days of symptom onset, Group 2
      (N = 17) - time to treatment greater than seven days but less than 90 days of
      symptom onset, and Group 3 (N = 4) - greater than 90 days of symptom onset. In
      Group 2, there was a significant improvement in pure tone average (P-value:
      0.005). Forty-seven percent of patients in this group had objective treatment
      response utilizing Wilson's criteria. Two patients had a complete recovery and
      six had a partial recovery. Hearing gains ranged from 10 dB (decibels) to 23 dB.
      Sixty-three percent of patients with objective improvement also had subjective
      improvement. In Group 3, none of the patients met Wilson's criteria for recovery.
      There was no statistically significant difference in response between patients
      treated with oral steroids only versus a combination of oral and IT steroids.
      Conclusion Patients with ISSNHL present to an otolaryngologist on average 55 days
      after symptom onset. There is statistically and clinically significant response
      to treatment in late presenters. Improvement can be seen up to three months from
      symptom onset. Oral steroid therapy is effective. IT steroid therapy may have an
      added benefit.

PMID- 29468102
TI  - Role of Stereotactic Radiosurgery in the Management of Multiple Metastases in the
      Region of the Motor Cortex: Long-term Survival in Three Cases.
AB  - The management of patients with multiple brain metastases, in contrast to those
      with solitary metastases, continues to evolve. Recent evidence suggests that
      aggressive microsurgical and radiosurgical management of patients with multiple
      brain metastases may lead to improved survival and quality of life. The three
      cases discussed in this report are examples of patients with multiple brain
      metastases who had excellent outcomes following treatment with microsurgical and
      radiosurgical approaches. A common feature of each patient is the presence of
      multiple metastases in the region of the motor cortex. The rationale for this
      selection is to demonstrate that aggressive management can have a favorable
      outcome despite the presence of multiple metastases in eloquent regions of the
      brain.

PMID- 29468103
TI  - Atypical Location of Intracerebral Hemorrhage in Moyamoya Disease.
AB  - Moyamoya disease is a chronic, progressive bilateral occlusion or stenosis of
      terminal internal carotid arteries as well as the proximal anterior and middle
      cerebral arteries. Hemorrhage of the splenium of the corpus callosum rarely
      occurs with moyamoya disease. In this article, we report a case of a 53-year-old
      woman diagnosed with moyamoya disease by cerebral angiography. She presented to
      the emergency department complaining of unsteadiness and a tendency to fall
      forward for one week. The patient was investigated with head computed tomography
      (CT) scan upon presentation revealing atypical location of hemorrhage in the
      corpus callosum, mainly in the splenium.

PMID- 29468104
TI  - Cerebellar Stroke Occupational Therapy and Physical Therapy Management from
      Intensive Care Unit to Outpatient: A Case Report.
AB  - Cerebellar stroke increases the risk of extensive physical disability and long
      term institutionalization. The purpose of this case report is to describe the 14
      month longitudinal rehabilitation management and outcomes from the intensive care
      unit, inpatient rehabilitation unit and outpatient care of a patient after
      cerebellar stroke. A goal of this case report is to provide rehabilitation
      clinicians with a long-term perspective and understanding of the course of
      recovery for a patient after cerebellar cerebrovascular accident or related
      injury. A 51-year-old healthy athletic female experienced acute bilateral
      cerebellar infarcts with subsequent craniotomy to remove infarcted areas. The
      patient had postoperative hemorrhages and hydrocephalus and was deemed to have a
      poor prognosis. Multimodal sensory stimulation and early mobility was performed
      until conventional neuromuscular reeducation interventions could be tolerated.
      Primary deficits included decreased proximal strength, whole body ataxia,
      vertical diplopia, dysphagia, difficulty communicating, and emotional lability.
      Fourteen months after the initial infarcts, the patient was able to reside in her
      own home with her husband, ambulate, and stand with assistance and perform most
      activities of daily living with standby or set-up assistance. This patient made
      significant progress toward safety and mobility and was able to return home
      despite the early discussion about a poor prognosis and a palliative care
      consultation. The complex, intensive course of rehabilitation elicited slow,
      steady, consistent gains. The patient's motivation and family involvement likely
      facilitated optimum outcomes.

PMID- 29468105
TI  - Smaller Radius Width in Women With Distal Radius Fractures Compared to Women
      Without Fractures.
AB  - Introduction Bone mineral density (BMD) measured using dual-energy x-ray
      absorptiometry (DXA) is typically used to assess fracture risk. However, other
      factors such as bone size and the forward momentum of a fall (a function of body
      size) can also potentially influence fracture risk, but are understudied. This
      report describes the characteristics of a cohort of Caucasian pre- and
      postmenopausal women with distal radius fractures (DRF) after falling onto an
      outstretched hand. Methods The fracture cohort comprised entries in an
      institutional review board-approved registry of study patients who had had DXA
      scans. For patients with DRF, the contralateral radius was scanned and BMD, T
      scores (used to define bone status as normal, osteopenic, or osteoporotic), and
      radius width were recorded. Generally, side-to-side (left-right) differences in
      bone size and BMD are small and, hence, the contralateral radius was considered a
      surrogate for bone status of the fractured radius. Apparently healthy women
      without fractures were used as race-, age-, and BMI-matched controls.   Results
      Premenopausal women < 49 years of age (mean age, 38 years) with DRF had
      significanty smaller radii width compared to matched controls. Mean radius BMD
      was in the normal range. As a group, the cohort was overweight based on mean BMI.
      Postmenopausal women > 50 years (mean age, 64 years) with DRF also had low radius
      width, but in contrast to the first group, this group had low peripheral and
      central BMD. Conclusions Women with DRF had contralateral and presumably
      fractured radii of bone width smaller than matched controls. As a group, these
      women were also overweight based on BMI. The smaller radius width may increase
      the risk for fracture irrespective of BMD, especially since larger body size
      would result in greater inertial force when falling while ambulating.

PMID- 29468106
TI  - A Case of Acute Left Main Coronary Obstruction Following Transcatheter Aortic
      Valve Implantation.
AB  - Transcatheter aortic valve implantation (TAVI) is a highly effective procedure in
      selected patients with severe degenerative aortic valve stenosis at high risk for
      conventional surgery. Coronary occlusion is a periprocedural life-threatening
      complication that despite its low frequency (?1%) is poorly predictable and
      requires immediate diagnosis and treatment. Herein, we report a coronary
      obstruction after transcatheter implantation of valve prosthesis, followed by
      coronary intervention with successful recanalization.

PMID- 29468107
TI  - Contrast-Enhanced Ultrasound-Guided Radiofrequency Ablation of Renal Tumors.
AB  - Although only limited long-term studies evaluating thermal ablation of renal
      masses have been performed, it appears that thermal ablation has a comparable 5
      year success rate to that of partial or total nephrectomy. This technique is
      often used in patients who are not good candidates for partial or total
      nephrectomy. Contrast-enhanced ultrasound (CEUS) has been recently approved by
      the Food and Drug Administration for characterization of focal liver lesions in
      adults and pediatric patients. CEUS can be used off label for renal applications
      and has been used for years in Europe and Asia. It has several advantages over
      contrast-enhanced computed tomography for use as the technique to guide and
      evaluate efficacy of thermal ablation of renal masses. These include the ability
      to visualize small amounts of enhancement, repeat dosing to evaluate efficacy of
      an ablation during a procedure, thin slice thickness, and real-time
      visualization. Ultrasound contrast is also non-nephrotoxic and non-hepatotoxic,
      allowing evaluation of patients with renal insufficiency. This article reviews
      the use of CEUS for the guidance and follow-up of thermal ablative procedures of
      renal masses.

PMID- 29468108
TI  - Nivolumab in Renal Cell Carcinoma: Current Trends and Future Perspectives.
AB  - Targeted agents form the backbone of most therapeutic strategies in advanced
      renal cell carcinoma (aRCC) but ultimately resistance develops and toxicity often
      leads to discontinuation of treatment, limiting the clinical benefits of these
      treatments. Nivolumab, a fully human IgG4 anti-PD-1 antibody, selectively blocks
      the interaction between PD-1 and its ligands PD-L1 and PD-L2 and provides a novel
      therapy option for patients with aRCC. In 2015, the pivotal phase III study
      CheckMate 025 led to the Food and Drug Administration approval of nivolumab in
      patients with aRCC who had received prior anti-angiogenic therapy, and in 2017,
      the phase III study CheckMate 214 showed that combined immunotherapy with
      nivolumab plus ipilimumab resulted in greater objective response rate and
      prolonged progression-free survival when compared with sunitinib in intermediate-
      and poor-risk patients with previously untreated aRCC. Early studies of nivolumab
      in association with anti-angiogenic therapy have generated enthusiasm and
      multiple combination trials are ongoing.

PMID- 29468109
TI  - Metabolic engineering of Escherichia coli for the biosynthesis of 2-pyrrolidone.
AB  - 2-Pyrrolidone is a valuable bulk chemical with myriad applications as a solvent,
      polymer precursor and active pharmaceutical intermediate. A novel 2-pyrrolidone
      synthase, ORF27, from Streptomyces aizunensis was identified to catalyze the ring
      closing dehydration of gamma-aminobutyrate. ORF27's tendency to aggregate was
      resolved by expression at low temperature and fusion to the maltose binding
      protein (MBP). Recombinant Escherichia coli was metabolically engineered for the
      production of 2-pyrrolidone from glutamate by expressing both the genes encoding
      GadB, a glutamate decarboxylase, and ORF27. Incorporation of a GadB mutant
      lacking H465 and T466, GadB_DeltaHT, improved the efficiency of one-pot 2
      pyrrolidone biosynthesis in vivo. When the recombinant E. coli strain expressing
      the E. coli GadB_DeltaHT mutant and the ORF27-MBP fusion was cultured in ZYM-5052
      medium containing 9 g/L of l-glutamate, 7.7 g/L of l-glutamate was converted to
      1.1 g/L of 2-pyrrolidone within 31 h, achieving 25% molar yield from the consumed
      substrate.

PMID- 29468110
TI  - Hyaluronan production and molecular weight is enhanced in pathway-engineered
      strains of lactate dehydrogenase-deficient Lactococcus lactis.
AB  - The potential advantages of hyaluronic acid (HA) production by metabolically
      engineered Lactococcus lactis is constrained by the lower molecular weight and
      yield of HA obtained in these strains, compared to natural producers. Earlier
      studies have correlated lower HA yield with excessive lactate production in L.
      lactis cultures (Chauhan et al., 2014). In the present study, a three-fold
      increase was observed in the amount as well as molecular weight of HA produced by
      recombinant ldh-mutant L. lactis strains. The diversion from lactate production
      in the ldh-mutant strains resulted in excess ethanol and acetoin production and
      higher NAD+/NADH ratio in these cultures. The initial NAD+/NADH ratio showed a
      positive correlation with HA molecular weight as well as with the HA-precursor
      ratio (UDP-GlcUA/UDP-GlcNAc). The influence of NAD+/NADH ratio on regulation of
      the concerned metabolic pathways was assessed by transcriptional analysis of key
      genes having putative binding sites of the NADH-binding transcriptional factor,
      Rex.

PMID- 29468111
TI  - Conversion of levoglucosan and cellobiosan by Pseudomonas putida KT2440.
AB  - Pyrolysis offers a straightforward approach for the deconstruction of plant cell
      wall polymers into bio-oil. Recently, there has been substantial interest in bio
      oil fractionation and subsequent use of biological approaches to selectively
      upgrade some of the resulting fractions. A fraction of particular interest for
      biological upgrading consists of polysaccharide-derived substrates including
      sugars and sugar dehydration products such as levoglucosan and cellobiosan, which
      are two of the most abundant pyrolysis products of cellulose. Levoglucosan can be
      converted to glucose-6-phosphate through the use of a levoglucosan kinase (LGK),
      but to date, the mechanism for cellobiosan utilization has not been demonstrated.
      Here, we engineer the microbe Pseudomonas putida KT2440 to use levoglucosan as a
      sole carbon and energy source through LGK integration. Moreover, we demonstrate
      that cellobiosan can be enzymatically converted to levoglucosan and glucose with
      beta-glucosidase enzymes from both Glycoside Hydrolase Family 1 and Family 3.
      beta-glucosidases are commonly used in both natural and industrial cellulase
      cocktails to convert cellobiose to glucose to relieve cellulase product
      inhibition and to facilitate microbial uptake of glucose. Using an exogenous beta
      glucosidase, we demonstrate that the engineered strain of P. putida can grow on
      levoglucosan up to 60 g/L and can also utilize cellobiosan. Overall, this study
      elucidates the biological pathway to co-utilize levoglucosan and cellobiosan,
      which will be a key transformation for the biological upgrading of pyrolysis
      derived substrates.

PMID- 29468112
TI  - Promiscuous plasmid replication in thermophiles: Use of a novel hyperthermophilic
      replicon for genetic manipulation of Clostridium thermocellum at its optimum
      growth temperature.
AB  - Clostridium thermocellum is a leading candidate for the consolidated
      bioprocessing of lignocellulosic biomass for the production of fuels and
      chemicals. A limitation to the engineering of this strain is the availability of
      stable replicating plasmid vectors for homologous and heterologous expression of
      genes that provide improved and/or novel pathways for fuel production. Current
      vectors relay on replicons from mesophilic bacteria and are not stable at the
      optimum growth temperature of C. thermocellum. To develop more thermostable
      genetic tools for C. thermocellum, we constructed vectors based on the
      hyperthermophilic Caldicellulosiruptor bescii replicon pBAS2. Autonomously
      replicating shuttle vectors based on pBAS2 reproducibly transformed C.
      thermocellum at 60  degrees C and were maintained in multiple copy. Promoters,
      selectable markers and plasmid replication proteins from C. bescii were
      functional in C. thermocellum. Phylogenetic analyses of the proteins contained on
      pBAS2 revealed that the replication initiation protein RepL is unique among
      thermophiles. These results suggest that pBAS2 may be a broadly useful replicon
      for other thermophilic Firmicutes.

PMID- 29468114
TI  - Mitochondrial targeting increases specific activity of a heterologous valine
      assimilation pathway in Saccharomyces cerevisiae.
AB  - Bio-based isobutantol is a sustainable 'drop in' substitute for petroleum-based
      fuels. However, well-studied production routes, such as the Ehrlich pathway, have
      yet to be commercialized despite more than a century of research. The more
      versatile bacterial valine catabolism may be a competitive alternate route
      producing not only an isobutanol precursor but several carboxylic acids with
      applications as biomonomers, and building blocks for other advanced biofuels.
      Here, we transfer the first two committed steps of the pathway from pathogenic
      Pseudomonas aeruginosa PAO1 to yeast to evaluate their activity in a safer model
      organism. Genes encoding the heteroligomeric branched chain keto-acid
      dehydrogenase (BCKAD; bkdA1, bkdA2, bkdB, lpdV), and the homooligomeric acyl-CoA
      dehydrogenase (ACD; acd1) were tagged with fluorescence epitopes and targeted for
      expression in either the mitochondria or cytoplasm of S. cerevisiae. We verified
      the localization of our constructs with confocal fluorescence microscopy before
      measuring the activity of tag-free constructs. Despite reduced heterologous
      expression of mitochondria-targeted enzymes, their specific activities were
      significantly improved with total enzyme activities up to 138% greater than those
      of enzymes expressed in the cytoplasm. In total, our results demonstrate that the
      choice of protein localization in yeast has significant impact on heterologous
      activity, and suggests a new path forward for isobutanol production.

PMID- 29468113
TI  - Interaction of storage carbohydrates and other cyclic fluxes with central
      metabolism: A quantitative approach by non-stationary 13C metabolic flux
      analysis.
AB  - 13C labeling experiments in aerobic glucose limited cultures of Saccharomyces
      cerevisiae at four different growth rates (0.054; 0.101, 0.207, 0.307 h-1) are
      used for calculating fluxes that include intracellular cycles (e.g., storage
      carbohydrate cycles, exchange fluxes with amino acids), which are rearranged
      depending on the growth rate. At low growth rates the impact of the storage
      carbohydrate recycle is relatively more significant than at high growth rates due
      to a higher concentration of these materials in the cell (up to 560-fold) and
      higher fluxes relative to the glucose uptake rate (up to 16%). Experimental
      observations suggest that glucose can be exported to the extracellular space, and
      that its source is related to storage carbohydrates, most likely via the export
      and subsequent extracellular breakdown of trehalose. This hypothesis is strongly
      supported by 13C-labeling experimental data, measured extracellular trehalose,
      and the corresponding flux estimations.

PMID- 29468115
TI  - An optimized method for accurate quantification of cell migration using human
      small intestine cells.
AB  - Quantifying the ability of a compound to modulate cell migration rate is a
      crucial part of many studies including those on chemotaxis, wound healing and
      cancer metastasis. Existing migration assays all have their strengths and
      weaknesses. The "scratch" assay is the most widely used because it seems
      appealingly simple and inexpensive. However, the scratch assay has some important
      limitations, as the tool introducing the "wound" might injure/stress the boundary
      cells and/or harm underlying matrix coatings, which in both cases will affect
      cell migration. This described method is a Cell Exclusion Zone Assay, in which
      cell-free areas are created by growing cells around removable silicone stoppers.
      Upon appropriate staining with fluorescent dyes and microscopically visualizing
      the monolayers, the migration rate is then quantified by counting the cells
      (nuclei) intruding the void area left by the silicone insert. In the current
      study human small intestine epithelial cells were seeded on a physiological
      substrate matrix to produce collectively migrating monolayers. Different
      substrates were tested to determine the optimal surface for enterocyte adherence
      and migration and morphological changes monitored. Recombinant human epidermal
      growth factor and osteopontin purified from urine were tested to see if the
      established migration assay produces accurate and reliable migration data with
      human small intestine cells. The obtained data accurately confirmed that the two
      bioactive proteins modulate cellular migration in a dose-dependent manner. The
      presented assay can likely be converted for use with other adherent cell lines or
      substrate matrices and allows for high throughput, while cost is kept low and
      versatility high. Co-staining can be applied in order to assay for cell death,
      different cell types, cell stress and others allowing intricate analysis of
      migration rate of mixed populations and correction for cell viability.

PMID- 29468116
TI  - Acidithiobacillus ferrooxidans's comprehensive model driven analysis of the
      electron transfer metabolism and synthetic strain design for biomining
      applications.
AB  - Acidithiobacillus ferrooxidans is a gram-negative chemolithoautotrophic gamma
      proteobacterium. It typically grows at an external pH of 2 using the oxidation of
      ferrous ions by oxygen, producing ferric ions and water, while fixing carbon
      dioxide from the environment. A. ferrooxidans is of great interest for biomining
      and environmental applications, as it can process mineral ores and alleviate the
      negative environmental consequences derived from the mining processes. In this
      study, the first genome-scale metabolic reconstruction of A. ferrooxidans ATCC
      23270 was generated (iMC507). A total of 587 metabolic and transport/exchange
      reactions, 507 genes and 573 metabolites organized in over 42 subsystems were
      incorporated into the model. Based on a new genetic algorithm approach, that
      integrates flux balance analysis, chemiosmotic theory, and physiological data,
      the proton translocation stoichiometry for a number of enzymes and maintenance
      parameters under aerobic chemolithoautotrophic conditions using three different
      electron donors were estimated. Furthermore, a detailed electron transfer and
      carbon flux distributions during chemolithoautotrophic growth using ferrous ion,
      tetrathionate and thiosulfate were determined and reported. Finally, 134 growth
      coupled designs were calculated that enables Extracellular Polysaccharide
      production. iMC507 serves as a knowledgebase for summarizing and categorizing the
      information currently available for A. ferrooxidans and enables the understanding
      and engineering of Acidithiobacillus and similar species from a comprehensive
      model-driven perspective for biomining applications.

PMID- 29468117
TI  - Dynamics of benzoate metabolism in Pseudomonas putida KT2440.
AB  - Soil microorganisms mineralize lignin-derived aromatic carbon sources using
      oxidative catabolic pathways, such as the beta-ketoadipate pathway. Although this
      aromatic pathway is one of the best-studied pathways in biochemistry, the
      complete pathway, including its regulation by aromatic carbon sources, has not
      been integrated into the metabolic network. In particular, information about the
      in vivo operation (e.g., kinetics and flux capacity) of the pathway is lacking.
      In this contribution, we use kinetic modeling and thermodynamic analysis to
      evaluate the in vivo operation of this key aromatic multi-step pathway. The
      resulting ab initio deterministic model of benzoate degradation via the beta
      ketoadipate (ortho-cleavage) pathway in Pseudomonas putida KT2440 is presented.
      The kinetic model includes mechanistic rate expressions for the enzymes and
      transport processes. The design and experimental validation of the model are
      driven by data generated from short-term perturbation experiments in a benzoate
      limited continuous culture. The results of rigorous modeling of the in vivo
      dynamics provide strong support for flux regulation by the benzoate transporter
      and the enzymes forming and cleaving catechol. Revisiting the beta-ketoadipate
      pathway might be valuable for applications in different fields, such as
      biochemistry and metabolic engineering, that use lignin monomers as a carbon
      source.

PMID- 29468118
TI  - Enhancing muconic acid production from glucose and lignin-derived aromatic
      compounds via increased protocatechuate decarboxylase activity.
AB  - The conversion of biomass-derived sugars and aromatic molecules to cis,cis
      muconic acid (referred to hereafter as muconic acid or muconate) has been of
      recent interest owing to its facile conversion to adipic acid, an important
      commodity chemical. Metabolic routes to produce muconate from both sugars and
      many lignin-derived aromatic compounds require the use of a decarboxylase to
      convert protocatechuate (PCA, 3,4-dihydroxybenzoate) to catechol (1,2
      dihydroxybenzene), two central aromatic intermediates in this pathway. Several
      studies have identified the PCA decarboxylase as a metabolic bottleneck, causing
      an accumulation of PCA that subsequently reduces muconate production. A recent
      study showed that activity of the PCA decarboxylase is enhanced by co-expression
      of two genetically associated proteins, one of which likely produces a flavin
      derived cofactor utilized by the decarboxylase. Using entirely genome-integrated
      gene expression, we have engineered Pseudomonas putida KT2440-derived strains to
      produce muconate from either aromatic molecules or sugars and demonstrate in both
      cases that co-expression of these decarboxylase associated proteins reduces PCA
      accumulation and enhances muconate production relative to strains expressing the
      PCA decarboxylase alone. In bioreactor experiments, co-expression increased the
      specific productivity (mg/g cells/h) of muconate from the aromatic lignin monomer
      p-coumarate by 50% and resulted in a titer of >15 g/L. In strains engineered to
      produce muconate from glucose, co-expression more than tripled the titer, yield,
      productivity, and specific productivity, with the best strain producing 4.92+/
      0.48 g/L muconate. This study demonstrates that overcoming the PCA decarboxylase
      bottleneck can increase muconate yields from biomass-derived sugars and aromatic
      molecules in industrially relevant strains and cultivation conditions.

PMID- 29468119
TI  - Improved sugar-free succinate production by Synechocystis sp. PCC 6803 following
      identification of the limiting steps in glycogen catabolism.
AB  - Succinate produced by microorganisms can replace currently used petroleum-based
      succinate but typically requires mono- or poly-saccharides as a feedstock. The
      cyanobacterium Synechocystis sp. PCC6803 can produce organic acids such as
      succinate from CO2 not supplemented with sugars under dark anoxic conditions
      using an unknown metabolic pathway. The TCA cycle in cyanobacteria branches into
      oxidative and reductive routes. Time-course analyses of the metabolome,
      transcriptome and metabolic turnover described here revealed dynamic changes in
      the metabolism of Synechocystis sp. PCC6803 cultivated under dark anoxic
      conditions, allowing identification of the carbon flow and rate-limiting steps in
      glycogen catabolism. Glycogen biosynthesized from CO2 assimilated during periods
      of light exposure is catabolized to succinate via glycolysis, the anaplerotic
      pathway, and the reductive TCA cycle under dark anoxic conditions. Expression of
      the phosphoenolpyruvate (PEP) carboxylase gene (ppc) was identified as a rate
      limiting step in succinate biosynthesis and this rate limitation was alleviated
      by ppc overexpression, resulting in improved succinate excretion. The sugar-free
      succinate production was further enhanced by the addition of bicarbonate. In vivo
      labeling with NaH13CO3 clearly showed carbon incorporation into succinate via the
      anaplerotic pathway. Bicarbonate is in equilibrium with CO2. Succinate production
      by Synechocystis sp. PCC6803 therefore holds significant promise for CO2 capture
      and utilization.

PMID- 29468120
TI  - The Saccharomyces cerevisiae pheromone-response is a metabolically active
      stationary phase for bio-production.
AB  - The growth characteristics and underlying metabolism of microbial production
      hosts are critical to the productivity of metabolically engineered pathways.
      Production in parallel with growth often leads to biomass/bio-product competition
      for carbon. The growth arrest phenotype associated with the Saccharomyces
      cerevisiae pheromone-response is potentially an attractive production phase
      because it offers the possibility of decoupling production from population
      growth. However, little is known about the metabolic phenotype associated with
      the pheromone-response, which has not been tested for suitability as a production
      phase. Analysis of extracellular metabolite fluxes, available transcriptomic
      data, and heterologous compound production (para-hydroxybenzoic acid) demonstrate
      that a highly active and distinct metabolism underlies the pheromone-response.
      These results indicate that the pheromone-response is a suitable production
      phase, and that it may be useful for informing synthetic biology design
      principles for engineering productive stationary phase phenotypes.

PMID- 29468121
TI  - Improving the flux distributions simulated with genome-scale metabolic models of
      Saccharomyces cerevisiae.
AB  - Genome-scale metabolic models (GEMs) can be used to evaluate genotype-phenotype
      relationships and their application to microbial strain engineering is increasing
      in popularity. Some of the algorithms used to simulate the phenotypes of mutant
      strains require the determination of a wild-type flux distribution. However, the
      accuracy of this reference, when calculated with flux balance analysis, has not
      been studied in detail before. Here, the wild-type simulations of selected GEMs
      for Saccharomyces cerevisiae have been analysed and most of the models tested
      predicted erroneous fluxes in central pathways, especially in the pentose
      phosphate pathway. Since the problematic fluxes were mostly related to areas of
      the metabolism consuming or producing NADPH/NADH, we have manually curated all
      reactions including these cofactors by forcing the use of NADPH/NADP+ in anabolic
      reactions and NADH/NAD+ for catabolic reactions. The curated models predicted
      more accurate flux distributions and performed better in the simulation of mutant
      phenotypes.

PMID- 29468122
TI  - A genetic screen for increasing metabolic flux in the isoprenoid pathway of
      Saccharomyces cerevisiae: Isolation of SPT15 mutants using the screen.
AB  - A genetic screen to identify mutants that can increase flux in the isoprenoid
      pathway of yeast has been lacking. We describe a carotenoid-based visual screen
      built with the core carotenogenic enzymes from the red yeast Rhodosporidium
      toruloides. Enzymes from this yeast displayed the required, higher capacity in
      the carotenoid pathway. The development also included the identification of the
      metabolic bottlenecks, primarily phytoene dehydrogenase, that was subjected to a
      directed evolution strategy to yield more active mutants. To further limit
      phytoene pools, a less efficient version of GGPP synthase was employed. The
      screen was validated with a known flux increasing gene, tHMG1. New mutants in the
      TATA binding protein SPT15 were isolated using this screen that increased the
      yield of carotenoids, and an alternate isoprenoid, alpha-Farnesene confirming
      increase in overall flux. The findings indicate the presence of previously
      unknown links to the isoprenoid pathway that can be uncovered using this screen.

PMID- 29468123
TI  - Molecular Cloning Designer Simulator (MCDS): All-in-one molecular cloning and
      genetic engineering design, simulation and management software for complex
      synthetic biology and metabolic engineering projects.
AB  - Molecular Cloning Designer Simulator (MCDS) is a powerful new all-in-one cloning
      and genetic engineering design, simulation and management software platform
      developed for complex synthetic biology and metabolic engineering projects. In
      addition to standard functions, it has a number of features that are either
      unique, or are not found in combination in any one software package: (1) it has a
      novel interactive flow-chart user interface for complex multi-step processes,
      allowing an integrated overview of the whole project; (2) it can perform a user
      defined workflow of cloning steps in a single execution of the software; (3) it
      can handle multiple types of genetic recombineering, a technique that is rapidly
      replacing classical cloning for many applications; (4) it includes experimental
      information to conveniently guide wet lab work; and (5) it can store results and
      comments to allow the tracking and management of the whole project in one
      platform. MCDS is freely available from https://mcds.codeplex.com.

PMID- 29468124
TI  - The impact of respiration and oxidative stress response on recombinant alpha
      amylase production by Saccharomyces cerevisiae.
AB  - Studying protein production is important for fundamental research on cell biology
      and applied research for biotechnology. Yeast Saccharomyces cerevisiae is an
      attractive workhorse for production of recombinant proteins as it does not
      secrete many endogenous proteins and it is therefore easy to purify a secreted
      product. However, recombinant production at high rates represents a significant
      metabolic burden for the yeast cells, which results in oxidative stress and
      ultimately affects the protein production capacity. Here we describe a method to
      reduce the overall oxidative stress by overexpressing the endogenous HAP1 gene in
      a S. cerevisiae strain overproducing recombinant alpha-amylase. We demonstrate
      how Hap1p can activate a set of oxidative stress response genes and meanwhile
      contribute to increase the metabolic rate of the yeast strains, therefore
      mitigating the negative effect of the ROS accumulation associated to protein
      folding and hence increasing the production capacity during batch fermentations.

PMID- 29468125
TI  - Enhanced fatty acid production in engineered chemolithoautotrophic bacteria using
      reduced sulfur compounds as energy sources.
AB  - Chemolithoautotrophic bacteria that oxidize reduced sulfur compounds, such as
      H2S, while fixing CO2 are an untapped source of renewable bioproducts from
      sulfide-laden waste, such as municipal wastewater. In this study, we report
      engineering of the chemolithoautotrophic bacterium Thiobacillus denitrificans to
      produce up to 52-fold more fatty acids than the wild-type strain when grown with
      thiosulfate and CO2. A modified thioesterase gene from E. coli ('tesA) was
      integrated into the T. denitrificans chromosome under the control of Pkan or one
      of two native T. denitrificans promoters. The relative strength of the two native
      promoters as assessed by fatty acid production in engineered strains was very
      similar to that assessed by expression of the cognate genes in the wild-type
      strain. This proof-of-principle study suggests that engineering sulfide-oxidizing
      chemolithoautotrophic bacteria to overproduce fatty acid-derived products merits
      consideration as a technology that could simultaneously produce renewable
      fuels/chemicals as well as cost-effectively remediate sulfide-contaminated
      wastewater.

PMID- 29468127
TI  - Quantifying complexity in metabolic engineering using the LASER database.
AB  - We previously introduced the LASER database (Learning Assisted Strain
      EngineeRing, https://bitbucket.org/jdwinkler/laser_release) (Winkler et al. 2015)
      to serve as a platform for understanding past and present metabolic engineering
      practices. Over the past year, LASER has been expanded by 50% to include over 600
      engineered strains from 450 papers, including their growth conditions, genetic
      modifications, and other information in an easily searchable format. Here, we
      present the results of our efforts to use LASER as a means for defining the
      complexity of a metabolic engineering "design". We evaluate two complexity
      metrics based on the concepts of construction difficulty and novelty. No
      correlation is observed between expected product yield and complexity, allowing
      minimization of complexity without a performance trade-off. We envision the use
      of such complexity metrics to filter and prioritize designs prior to
      implementation of metabolic engineering efforts, thereby potentially reducing the
      time, labor, and expenses of large-scale projects. Possible future developments
      based on an expanding LASER database are then discussed.

PMID- 29468126
TI  - Computational metabolic engineering strategies for growth-coupled biofuel
      production by Synechocystis.
AB  - Chemical and fuel production by photosynthetic cyanobacteria is a promising
      technology but to date has not reached competitive rates and titers. Genome-scale
      metabolic modeling can reveal limitations in cyanobacteria metabolism and guide
      genetic engineering strategies to increase chemical production. Here, we used
      constraint-based modeling and optimization algorithms on a genome-scale model of
      Synechocystis PCC6803 to find ways to improve productivity of fermentative, fatty
      acid, and terpene-derived fuels. OptGene and MOMA were used to find heuristics
      for knockout strategies that could increase biofuel productivity. OptKnock was
      used to find a set of knockouts that led to coupling between biofuel and growth.
      Our results show that high productivity of fermentation or reversed beta
      oxidation derived alcohols such as 1-butanol requires elimination of NADH sinks,
      while terpenes and fatty-acid based fuels require creating imbalances in
      intracellular ATP and NADPH production and consumption. The FBA-predicted
      productivities of these fuels are at least 10-fold higher than those reported so
      far in the literature. We also discuss the physiological and practical
      feasibility of implementing these knockouts. This work gives insight into how
      cyanobacteria could be engineered to reach competitive biofuel productivities.

PMID- 29468128
TI  - The expression of glycerol facilitators from various yeast species improves
      growth on glycerol of Saccharomyces cerevisiae.
AB  - Glycerol is an abundant by-product during biodiesel production and additionally
      has several assets compared to sugars when used as a carbon source for growing
      microorganisms in the context of biotechnological applications. However, most
      strains of the platform production organism Saccharomyces cerevisiae grow poorly
      in synthetic glycerol medium. It has been hypothesized that the uptake of
      glycerol could be a major bottleneck for the utilization of glycerol in S.
      cerevisiae. This species exclusively relies on an active transport system for
      glycerol uptake. This work demonstrates that the expression of predicted glycerol
      facilitators (Fps1 homologues) from superior glycerol-utilizing yeast species
      such as Pachysolen tannophilus, Komagataella pastoris, Yarrowia lipolytica and
      Cyberlindnera jadinii significantly improves the growth performance on glycerol
      of the previously selected glycerol-consuming S. cerevisiae wild-type strain (CBS
      6412-13A). The maximum specific growth rate increased from 0.13 up to 0.18 h-1
      and a biomass yield coefficient of 0.56 gDW/gglycerol was observed. These results
      pave the way for exploiting the assets of glycerol in the production of fuels,
      chemicals and pharmaceuticals based on baker's yeast.

PMID- 29468129
TI  - Conversion and assimilation of furfural and 5-(hydroxymethyl)furfural by
      Pseudomonas putida KT2440.
AB  - The sugar dehydration products, furfural and 5-(hydroxymethyl)furfural (HMF), are
      commonly formed during high-temperature processing of lignocellulose, most often
      in thermochemical pretreatment, liquefaction, or pyrolysis. Typically, these two
      aldehydes are considered major inhibitors in microbial conversion processes. Many
      microbes can convert these compounds to their less toxic, dead-end alcohol
      counterparts, furfuryl alcohol and 5-(hydroxymethyl)furfuryl alcohol. Recently,
      the genes responsible for aerobic catabolism of furfural and HMF were discovered
      in Cupriavidus basilensis HMF14 to enable complete conversion of these compounds
      to the TCA cycle intermediate, 2-oxo-glutarate. In this work, we engineer the
      robust soil microbe, Pseudomonas putida KT2440, to utilize furfural and HMF as
      sole carbon and energy sources via complete genomic integration of the 12 kB hmf
      gene cluster previously reported from Burkholderia phytofirmans. The common
      intermediate, 2-furoic acid, is shown to be a bottleneck for both furfural and
      HMF metabolism. When cultured on biomass hydrolysate containing representative
      amounts of furfural and HMF from dilute-acid pretreatment, the engineered strain
      outperforms the wild type microbe in terms of reduced lag time and enhanced
      growth rates due to catabolism of furfural and HMF. Overall, this study
      demonstrates that an approach for biological conversion of furfural and HMF,
      relative to the typical production of dead-end alcohols, enables both enhanced
      carbon conversion and substantially improves tolerance to hydrolysate inhibitors.
      This approach should find general utility both in emerging aerobic processes for
      the production of fuels and chemicals from biomass-derived sugars and in the
      biological conversion of high-temperature biomass streams from liquefaction or
      pyrolysis where furfural and HMF are much more abundant than in biomass
      hydrolysates from pretreatment.

PMID- 29468130
TI  - Synechocystis PCC 6803 overexpressing RuBisCO grow faster with increased
      photosynthesis.
AB  - The ribulose-1,5-bisphosphate (RuBP) oxygenation reaction catalyzed by Ribulose
      1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is competing with carboxylation,
      being negative for both energy and carbon balances in photoautotrophic organisms.
      This makes RuBisCO one of the bottlenecks for oxygenic photosynthesis and carbon
      fixation. In this study, RuBisCO was overexpressed in the unicellular
      cyanobacterium Synechocystis PCC 6803. Relative RuBisCO levels in the engineered
      strains FL50 and FL52 increased 2.1 times and 1.4 times, respectively, and both
      strains showed increased growth, photosynthesis and in vitro RuBisCO activity.
      The oxygen evolution rate increased by 54% and 42% on per chlorophyll basis,
      while the in vitro RuBisCO activity increased by 52% and 8.6%, respectively. The
      overexpressed RuBisCO were tagged with a FLAG tag, in strain FL50 on the N
      terminus of the large subunit while in strain FL52 on the C terminus of the small
      subunit. The presence of a FLAG tag enhanced transcription of the genes encoding
      RuBisCO, and, with high possibility, also enhanced the initiation of translation
      or stability of the enzyme. However, when using a streptavidin-binding tag II
      (strep-tag II), we did not observe a similar effect. Tagged RuBisCO offers an
      opportunity for further studying RuBisCO expression and stability. Increased
      levels of RuBisCO can further improve photosynthesis and growth in the
      cyanobacterium Synechocystis PCC 6803 under certain growth conditions.

PMID- 29468131
TI  - Selection Finder (SelFi): A computational metabolic engineering tool to enable
      directed evolution of enzymes.
AB  - Directed evolution of enzymes consists of an iterative process of creating mutant
      libraries and choosing desired phenotypes through screening or selection until
      the enzymatic activity reaches a desired goal. The biggest challenge in directed
      enzyme evolution is identifying high-throughput screens or selections to isolate
      the variant(s) with the desired property. We present in this paper a
      computational metabolic engineering framework, Selection Finder (SelFi), to
      construct a selection pathway from a desired enzymatic product to a cellular host
      and to couple the pathway with cell survival. We applied SelFi to construct
      selection pathways for four enzymes and their desired enzymatic products xylitol,
      D-ribulose-1,5-bisphosphate, methanol, and aniline. Two of the selection pathways
      identified by SelFi were previously experimentally validated for engineering
      Xylose Reductase and RuBisCO. Importantly, SelFi advances directed evolution of
      enzymes as there is currently no known generalized strategies or computational
      techniques for identifying high-throughput selections for engineering enzymes.

PMID- 29468133
TI  - Palliative surgery for Krukenberg tumors - 12-year experience and review of the
      literature.
AB  - AIM: To determine the clinical characteristics of patients undergoing palliative
      surgery for Krukenberg tumors, including disease presentation, outcomes, and
      prognostic factors. METHODS: This was a retrospective clinical study of all
      patients who underwent palliative surgery for Krukenberg tumors between January
      2004 and December 2015. Patient information was obtained from inpatient and
      outpatient case notes as well as the hospital electronic records. Patients who
      underwent potentially curative resection, and patients with Krukenberg tumors who
      did not undergo surgery were also excluded from the study. Palliative surgery was
      defined as those performed for either alleviation of symptoms or for asymptomatic
      patients for whom surgical removal of the tumors were deemed necessary following
      a multidisciplinary consensus. Tumors were diagnosed pre-operatively by computed
      tomography scans and all had histologic confirmation of the surgical specimens.
      RESULTS: Over the study duration, 38 female patients underwent palliative surgery
      for Krukenberg tumors at our institution. Mean age was 54.2 +/- 11.7 years. The
      colon was the most frequent primary source of metastases (n = 21) followed by the
      stomach (n = 4). Prophylactic palliative surgery was performed for eight (21.1%)
      asymptomatic patients. Median post-operative length of stay was 8 d (IQR 6-12 d).
      Five patients (13.2%) experienced post-operative complications, although high
      grade morbidity was only seen in one patient (2.6%). Median overall survival from
      surgery was 17 mo (95%CI: 12.1-21.9) at a median follow-up duration of 12 mo (IQR
      8-17 mo). The median survival was shorter for patients who underwent emergency
      surgery, younger patients, those with a colorectal primary, larger tumors, or
      synchronous peritoneal or hepatic metastases. CONCLUSION: Palliative surgery for
      Krukenberg tumors can be performed safely with acceptable complication rates.
      Bilateral oophorectomy should be performed to prevent the risk of symptomatic
      contralateral tumors.

PMID- 29468132
TI  - Does low volume high-intensity interval training elicit superior benefits to
      continuous low to moderate-intensity training in cancer survivors?
AB  - AIM: To determine the impact of low volume high-intensity interval training
      (LVHIIT) and continuous low to moderate-intensity exercise training (CLMIT) on
      cardiovascular disease (CVD) risk and health outcomes in cancer survivors.
      METHODS: Sedentary cancer survivors (n = 75, aged 51 +/- 12 year) within 24
      months of diagnosis, were randomised into three groups for 12 wk of LVHIIT (n =
      25), CLMIT (n = 25) or control group (n = 25). The exercise intervention involved
      36 sessions (three sessions per week). The LVHIIT group performed 7 x 30 s
      intervals (>= 85% predicted maximal heart rate) with a 60 s rest between
      intervals, and the CLMIT group performed continuous aerobic training for 20 min
      (<= 55% predicted maximal heart rate) on a stationary bike. Outcome variables
      were measured at baseline and at 12 weeks and analysed using a 3 x 2 (group x
      time) repeated measures ANCOVA to evaluate main and interaction effects. RESULTS:
      Significant improvements (time) were observed for seven of the 22 variables (ES
      0.35-0.97, P <= 0.05). There was an interaction effect (P < 0.01) after 12 wk in
      the LVHIIT group for six-minute walk test (P < 0.01; d = 0.97; 95%CI: 0.36, 1.56;
      large), sit to stand test (P < 0.01; d = -0.83; 95%CI: -1.40, -0.22; large ) and
      waist circumference reduction (P = 0.01; d = -0.48; 95%CI: -1.10, 0.10; medium).
      An interaction effect (P < 0.01) was also observed for quality of life in both
      the LVHIIT (d = 1.11; 95%CI: 0.50, 1.72; large) and CLMIT (d = 0.57; 95%CI: 
      0.00, 1.20; moderate) compared with the control group (d = -0.15; 95%CI: -0.95,
      0.65; trivial). CONCLUSION: Low-volume high-intensity training shows promise as
      an effective exercise prescription within the cancer population, showing greater
      improvements in cardio-respiratory fitness, lower body strength and waist
      circumference compared with traditional CLMIT and control groups. Both LVHIIT and
      CLMIT improved quality of life. A proposed benefit of LVHIIT is the short
      duration (3 min) of exercise required, which may entice more cancer survivors to
      participate in exercise, improving health outcomes and lowing the risk of CVD.

PMID- 29468134
TI  - Yttrium-90 microsphere selective internal radiation therapy for liver metastases
      following systemic chemotherapy and surgical resection for metastatic
      adrenocortical carcinoma.
AB  - Adrenocortical carcinoma (ACC) is a rare malignancy with generally poor outcomes
      and limited treatment options. While surgical resection can be curative for early
      local disease, most patients present with advanced ACC owing to nonspecific
      symptoms. For those patients, treatment options include systemic chemotherapy and
      locoregional therapies including radiofrequency ablation and transarterial
      chemoembolization. We present the first reported case of utilizing yttrium-90
      microsphere selective internal radiation therapy (SIRT) in combination with first
      line EDP-M (Etoposide, Doxorubicin, Cisplatin, Mitotane) chemotherapy and
      debulking surgical primary tumor resection for treatment of metastatic ACC.
      Stable complete radiologic response has been maintained after twelve months with
      resolution of clinical symptoms. These findings prompt the need for further
      consideration and studies to elucidate the role of SIRT in combination with
      systemic and surgical treatment for metastatic ACC.

PMID- 29468135
TI  - Optimal surgical approach for the treatment of Quervains disease: A surgical
      anatomical study.
AB  - AIM: To determine which of the common used incision techniques has the lowest
      chance of iatrogenic damage to the nerves which at risk are the superficial
      branch of the radial nerve (SBRN) and the Lateral Antebrachial Cutaneous Nerve
      (LABCN). METHODS: Twenty embalmed arms were dissected and the course of the SBRN
      and the LABCN in each individual arm was marked and the distance between the two
      branches of the SBRN at the location of the First Extensor Compartment (FEC) was
      measured. This data was used as input in a visualization tool called Computer
      Assisted Anatomy Mapping (CASAM) to map the course of the nerves in each
      individual arm. RESULTS: This image visualizes that in 90% of the arms, one
      branch of the SBRN crosses the FEC and one branch runs volar to the compartment.
      The distance between the two branches was 7.8 mm at the beginning of the FEC and
      10.2 mm at the end. Finally the angle of incision at which the chance of damage
      to the nerves is lowest, is 19.4 degrees volar to the radius. CONCLUSION: CASAM
      shows the complexity of the course of the SBRN over the FEC. None of the four
      widely used incision techniques has a significantly lower chance of iatrogenic
      nerve damage. Surgical skills are paramount to prevent iatrogenic nerve damage.

PMID- 29468136
TI  - Retinoic acid receptor beta promoter methylation and risk of cervical cancer.
AB  - Cervical cancer is one of the leading causes of death in women worldwide,
      particularly in developing countries. Human papillomavirus has been reported as
      one of the key etiologic factors in cervical carcinoma. Likewise, epigenetic
      aberrations have ability to regulate cancer pathogenesis and progression. Recent
      research suggested that methylation has been detected already at precancerous
      stages, which methylation markers may have significant value in cervical cancer
      screening. The retinoic acid receptor beta (RARbeta) gene, a potential tumor
      suppressor gene, is usually expressed in normal epithelial tissue. Methylation of
      CpG islands in the promoter region of the RARbeta gene has been found to be
      associated with the development of cervical cancer. To investigate whether
      RARbeta methylation is a potential biomarker that predicts the progression of
      invasive cancer, we reviewed 14 previously published articles related to RARbeta
      methylation. The majority of them demonstrated that the frequency of RARbeta
      promoter methylation was significantly correlated with the severity of cervical
      epithelium abnormalities. However, methylation of a single gene may not represent
      the best approach for predicting disease prognosis. Analyzing combinations of
      aberrant methylation of multiple genes may increase the sensitivity, and thus
      this approach may serve as a better tool for predicting disease prognosis.

PMID- 29468137
TI  - Identification of various cell culture models for the study of Zika virus.
AB  - AIM: To identify cell culture models supportive for Zika virus (ZIKV)
      replication. METHODS: Various human and non-human cell lines were infected with a
      defined amount of ZIKV Polynesia strain. Cells were analyzed 48 h post infection
      for the amount of intracellular and extracellular viral genomes and infectious
      viral particles by quantitative real-time PCR and virus titration assay. The
      extent of replication was monitored by immunofluorescence and western blot
      analysis by using Env and NS1 specific antibodies. Innate immunity was assayed by
      luciferase reporter assay and immunofluorescence analysis. RESULTS: All
      investigated cell lines except CHO cells supported infection, replication and
      release of ZIKV. While in infected A549 and Vero cells a pronounced cytopathic
      effect was observed COS7, 293T and Huh7.5 cells were most resistant. Although the
      analyzed cell lines released comparable amounts of viral genomes to the
      supernatant significant differences were found for the number of infectious viral
      particles. The neuronal cell lines N29.1 and SH-SY5Y released 100 times less
      infectious viral particles than Vero-, A549- or 293T-cells. However there is no
      strict correlation between the amount of produced viral particles and the
      induction of an interferon response in the analyzed cell lines. CONCLUSION: The
      investigated cell lines with their different tissue origins and diverging ZIKV
      susceptibility display a toolbox for ZIKV research.

PMID- 29468138
TI  - Editorial: Inter-Organelle Calcium Communication in Cancer.

PMID- 29468139
TI  - Hyperspectral Imaging and K-Means Classification for Histologic Evaluation of
      Ductal Carcinoma In Situ.
AB  - Hyperspectral imaging (HSI) is a non-invasive optical imaging modality that shows
      the potential to aid pathologists in breast cancer diagnoses cases. In this
      study, breast cancer tissues from different patients were imaged by a
      hyperspectral system to detect spectral differences between normal and breast
      cancer tissues. Tissue samples mounted on slides were identified from 10
      different patients. Samples from each patient included both normal and ductal
      carcinoma tissue, both stained with hematoxylin and eosin stain and unstained.
      Slides were imaged using a snapshot HSI system, and the spectral reflectance
      differences were evaluated. Analysis of the spectral reflectance values indicated
      that wavelengths near 550 nm showed the best differentiation between tissue
      types. This information was used to train image processing algorithms using
      supervised and unsupervised data. The K-means method was applied to the
      hyperspectral data cubes, and successfully detected spectral tissue differences
      with sensitivity of 85.45%, and specificity of 94.64% with true negative rate of
      95.8%, and false positive rate of 4.2%. These results were verified by ground
      truth marking of the tissue samples by a pathologist. In the hyperspectral image
      analysis, the image processing algorithm, K-means, shows the greatest potential
      for building a semi-automated system that could identify and sort between normal
      and ductal carcinoma in situ tissues.

PMID- 29468140
TI  - Posttranslational Modifications of Pyruvate Kinase M2: Tweaks that Benefit
      Cancer.
AB  - Cancer cells rewire metabolism to meet biosynthetic and energetic demands. The
      characteristic increase in glycolysis, i.e., Warburg effect, now considered as a
      hallmark, supports cancer in various ways. To attain such metabolic reshuffle,
      cancer cells preferentially re-express the M2 isoform of pyruvate kinase (PKM2,
      M2-PK) and alter its quaternary structure to generate less-active PKM2 dimers.
      The relatively inactive dimers cause the accumulation of glycolytic intermediates
      that are redirected into anabolic pathways. In addition, dimeric PKM2 also
      benefits cancer cells through various non-glycolytic moonlight functions, such as
      gene transcription, protein kinase activity, and redox balance. A large body of
      data have shown that several distinct posttranslation modifications (PTMs)
      regulate PKM2 in a way that benefits cancer growth, e.g., formation of PKM2
      dimers. This review discusses the recent advancements in our understanding of
      various PTMs and the benefits they impart to the sustenance of cancer.
      Understanding the PTMs in PKM2 is crucial to assess their therapeutic potential
      and to design novel anticancer strategies.

PMID- 29468142
TI  - Helicobacter pylori Type IV Secretion System and Its Adhesin Subunit, CagL,
      Mediate Potent Inflammatory Responses in Primary Human Endothelial Cells.
AB  - The Gram-negative bacterium, Helicobacter pylori, causes chronic gastritis,
      peptic ulcers, and gastric cancer in humans. Although the gastric epithelium is
      the primary site of H. pylori colonization, H. pylori can gain access to deeper
      tissues. Concurring with this notion, H. pylori has been found in the vicinity of
      endothelial cells in gastric submucosa. Endothelial cells play crucial roles in
      innate immune response, wound healing and tumorigenesis. This study examines the
      molecular mechanisms by which H. pylori interacts with and triggers inflammatory
      responses in endothelial cells. We observed that H. pylori infection of primary
      human endothelial cells stimulated secretion of the key inflammatory cytokines,
      interleukin-6 (IL-6) and interleukin-8 (IL-8). In particular, IL-8, a potent
      chemokine and angiogenic factor, was secreted by H. pylori-infected endothelial
      cells to levels ~10- to 20-fold higher than that typically observed in H. pylori
      infected gastric epithelial cells. These inflammatory responses were triggered by
      the H. pylori type IV secretion system (T4SS) and the T4SS-associated adhesin
      CagL, but not the translocation substrate CagA. Moreover, in contrast to integrin
      alpha5beta1 playing an essential role in IL-8 induction by H. pylori upon
      infection of gastric epithelial cells, both integrin alpha5beta1 and integrin
      alphavbeta3 were dispensable for IL-8 induction in H. pylori-infected endothelial
      cells. However, epidermal growth factor receptor (EGFR) is crucial for mediating
      the potent H. pylori-induced IL-8 response in endothelial cells. This study
      reveals a novel mechanism by which the H. pylori T4SS and its adhesin subunit,
      CagL, may contribute to H. pylori pathogenesis by stimulating the endothelial
      innate immune responses, while highlighting EGFR as a potential therapeutic
      target for controlling H. pylori-induced inflammation.

PMID- 29468143
TI  - Metagenomic Characterization of the Human Intestinal Microbiota in Fecal Samples
      from STEC-Infected Patients.
AB  - The human intestinal microbiota is a homeostatic ecosystem with a remarkable
      impact on human health and the disruption of this equilibrium leads to an
      increased susceptibility to infection by numerous pathogens. In this study, we
      used shotgun metagenomic sequencing and two different bioinformatic approaches,
      based on mapping of the reads onto databases and on the reconstruction of
      putative draft genomes, to investigate possible changes in the composition of the
      intestinal microbiota in samples from patients with Shiga Toxin-producing E. coli
      (STEC) infection compared to healthy and healed controls, collected during an
      outbreak caused by a STEC O26:H11 infection. Both the bioinformatic procedures
      used, produced similar result with a good resolution of the taxonomic profiles of
      the specimens. The stool samples collected from the STEC infected patients showed
      a lower abundance of the members of Bifidobacteriales and Clostridiales orders in
      comparison to controls where those microorganisms predominated. These differences
      seemed to correlate with the STEC infection although a flexion in the relative
      abundance of the Bifidobacterium genus, part of the Bifidobacteriales order, was
      observed also in samples from Crohn's disease patients, displaying a STEC
      unrelated dysbiosis. The metagenomics also allowed to identify in the STEC
      positive samples, all the virulence traits present in the genomes of the STEC O26
      that caused the outbreak as assessed through isolation of the epidemic strain and
      whole genome sequencing. The results shown represent a first evidence of the
      changes occurring in the intestinal microbiota of children in the course of STEC
      infection and indicate that metagenomics may be a promising tool for the culture
      independent clinical diagnosis of the infection.

PMID- 29468144
TI  - Vaccine-Mediated Mechanisms Controlling Replication of Francisella tularensis in
      Human Peripheral Blood Mononuclear Cells Using a Co-culture System.
AB  - Cell-mediated immunity (CMI) is normally required for efficient protection
      against intracellular infections, however, identification of correlates is
      challenging and they are generally lacking. Francisella tularensis is a highly
      virulent, facultative intracellular bacterium and CMI is critically required for
      protection against the pathogen, but how this is effectuated in humans is poorly
      understood. To understand the protective mechanisms, we established an in vitro
      co-culture assay to identify how control of infection of F. tularensis is
      accomplished by human cells and hypothesized that the model will mimic in vivo
      immune mechanisms. Non-adherent peripheral blood mononuclear cells (PBMCs) were
      expanded with antigen and added to cultures with adherent PBMC infected with the
      human vaccine strain, LVS, or the highly virulent SCHU S4 strain. Intracellular
      numbers of F. tularensis was followed for 72 h and secreted and intracellular
      cytokines were analyzed. Addition of PBMC expanded from naive individuals, i.e.,
      those with no record of immunization to F. tularensis, generally resulted in
      little or no control of intracellular bacterial growth, whereas addition of PBMC
      from a majority of F. tularensis-immune individuals executed static and sometimes
      cidal effects on intracellular bacteria. Regardless of infecting strain,
      statistical differences between the two groups were significant, P < 0.05.
      Secretion of 11 cytokines was analyzed after 72 h of infection and significant
      differences with regard to secretion of IFN-gamma, TNF, and MIP-1beta was
      observed between immune and naive individuals for LVS-infected cultures. Also, in
      LVS-infected cultures, CD4 T cells from vaccinees, but not CD8 T cells, showed
      significantly higher expression of IFN-gamma, MIP-1beta, TNF, and CD107a than
      cells from naive individuals. The co-culture system appears to identify
      correlates of immunity that are relevant for the understanding of mechanisms of
      the protective host immunity to F. tularensis.

PMID- 29468145
TI  - Editorial: International Partnerships for Strengthening Health Care Workforce
      Capacity: Models of Collaborative Education.

PMID- 29468141
TI  - Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan
      Metabolism.
AB  - The gut microbiota influences the health of the host, especially with regard to
      gut immune homeostasis and the intestinal immune response. In addition to serving
      as a nutrient enhancer, L-tryptophan (Trp) plays crucial roles in the balance
      between intestinal immune tolerance and gut microbiota maintenance. Recent
      discoveries have underscored that changes in the microbiota modulate the host
      immune system by modulating Trp metabolism. Moreover, Trp, endogenous Trp
      metabolites (kynurenines, serotonin, and melatonin), and bacterial Trp
      metabolites (indole, indolic acid, skatole, and tryptamine) have profound effects
      on gut microbial composition, microbial metabolism, the host's immune system, the
      host-microbiome interface, and host immune system-intestinal microbiota
      interactions. The aryl hydrocarbon receptor (AhR) mediates the regulation of
      intestinal immunity by Trp metabolites (as ligands of AhR), which is beneficial
      for immune homeostasis. Among Trp metabolites, AhR ligands consist of endogenous
      metabolites, including kynurenine, kynurenic acid, xanthurenic acid, and
      cinnabarinic acid, and bacterial metabolites, including indole, indole propionic
      acid, indole acetic acid, skatole, and tryptamine. Additional factors, such as
      aging, stress, probiotics, and diseases (spondyloarthritis, irritable bowel
      syndrome, inflammatory bowel disease, colorectal cancer), which are associated
      with variability in Trp metabolism, can influence Trp-microbiome-immune system
      interactions in the gut and also play roles in regulating gut immunity. This
      review clarifies how the gut microbiota regulates Trp metabolism and identifies
      the underlying molecular mechanisms of these interactions. Increased mechanistic
      insight into how the microbiota modulates the intestinal immune system through
      Trp metabolism may allow for the identification of innovative microbiota-based
      diagnostics, as well as appropriate nutritional supplementation of Trp to prevent
      or alleviate intestinal inflammation. Moreover, this review provides new insight
      regarding the influence of the gut microbiota on Trp metabolism. Additional
      comprehensive analyses of targeted Trp metabolites (including endogenous and
      bacterial metabolites) are essential for experimental preciseness, as the
      influence of the gut microbiota cannot be neglected, and may explain
      contradictory results in the literature.

PMID- 29468146
TI  - Antioxidant Phytochemicals in Fresh Produce: Exploitation of Genotype Variation
      and Advancements in Analytical Protocols.
AB  - Horticultural commodities (fruit and vegetables) are the major dietary source of
      several bioactive compounds of high nutraceutical value for humans, including
      polyphenols, carotenoids and vitamins. The aim of the current review was dual.
      Firstly, toward the eventual enhancement of horticultural crops with bio
      functional compounds, the natural genetic variation in antioxidants found in
      different species and cultivars/genotypes is underlined. Notably, some landraces
      and/or traditional cultivars have been characterized by substantially higher
      phytochemical content, i.e., small tomato of Santorini island (cv. "Tomataki
      Santorinis") possesses appreciably high amounts of ascorbic acid (AsA). The
      systematic screening of key bioactive compounds in a wide range of germplasm for
      the identification of promising genotypes and the restoration of key gene
      fractions from wild species and landraces may help in reducing the loss of agro
      biodiversity, creating a healthier "gene pool" as the basis of future adaptation.
      Toward this direction, large scale comparative studies in different
      cultivars/genotypes of a given species provide useful insights about the ones of
      higher nutritional value. Secondly, the advancements in the employment of
      analytical techniques to determine the antioxidant potential through a
      convenient, easy and fast way are outlined. Such analytical techniques include
      electron paramagnetic resonance (EPR) and infrared (IR) spectroscopy,
      electrochemical, and chemometric methods, flow injection analysis (FIA), optical
      sensors, and high resolution screening (HRS). Taking into consideration that
      fruits and vegetables are complex mixtures of water- and lipid-soluble
      antioxidants, the exploitation of chemometrics to develop "omics" platforms
      (i.e., metabolomics, foodomics) is a promising tool for researchers to decode
      and/or predict antioxidant activity of fresh produce. For industry, the use of
      optical sensors and IR spectroscopy is recommended to estimate the antioxidant
      activity rapidly and at low cost, although legislation does not allow its
      correlation with health claims.

PMID- 29468147
TI  - Systematic Chemical Analysis Approach Reveals Superior Antioxidant Capacity via
      the Synergistic Effect of Flavonoid Compounds in Red Vegetative Tissues.
AB  - The flavonoid system comprises an abundance of compounds with multiple functions;
      however, their potential synergism in antioxidant function remains unclear. We
      established an approach using ever-red (RL) and ever-green leaves (GL) of
      crabapple cultivars during their development to determine interrelationships
      among flavonoid compounds. RL scored significantly better than GL in terms of the
      type, composition, and diversity of flavonoids than GL. Principal component
      analysis predicted flavonoids in RL to have positive interaction effects, and the
      total antioxidant capacity was significantly higher than the sum of antioxidant
      capacities of the individual compounds. This synergy was verified by the high
      antioxidant capacity in rat serum after feeding on red leaves. Our findings
      suggest that the synergistic effect is a result of the high transcription levels
      regulated by McMYBs in RL. In summary, individual flavonoids cooperate in a
      flavonoid system, thus producing a synergistic antioxidant effect, and the
      approach used herein can provide insights into the roles of flavonoids and other
      compounds in future studies.

PMID- 29468149
TI  - Improved Stable Isotope Dilution Assay for Dietary Folates Using LC-MS/MS and Its
      Application to Strawberries.
AB  - Folates play an important role in the human body and a deficiency of this vitamin
      can cause several diseases. Therefore, a reliable analytical method is crucial
      for the determination of folate vitamers in strawberries and other dietary folate
      sources. A stable isotope dilution LC-MS/MS method for analyzing folates in food
      was developed and validated. The folate vitamers Pteroylmonoglutamic acid,
      tetrahydrofolate, 5-methyltetrahydrofolate, and 5-formyltetrahydrofolate were
      quantified using 13C-labeled internal standards. Validation of the assay was
      accomplished by determining linearity, precision, recovery, limit of detection,
      and limit of quantification and revealed to be a precise, sensitive, and accurate
      method to determine folate vitamers. Strawberries are worldwide consumed and
      known to be a good dietary source of nutritive compounds. Using this method,
      folate concentrations in selected commercial strawberry cultivars and
      experimental breeding lines grown in Germany and Australia were investigated.
      Total folates varied from 59 to 153 MUg/100 g on fresh weight basis. Furthermore,
      folate content after lyophilizing or freezing did not show any significant
      differences compared to fresh strawberries. However, significant losses of total
      folates in pureed strawberries could be observed after 5 days of storage with
      only 16% of the original concentration retained. In summary, some of the
      investigated strawberry cultivars/breeding lines can be considered as rich
      dietary sources of natural folates.

PMID- 29468150
TI  - Editorial: Antimicrobial and Anticancer Peptides.

PMID- 29468148
TI  - Polyamines: Bio-Molecules with Diverse Functions in Plant and Human Health and
      Disease.
AB  - Biogenic amines-polyamines (PAs), particularly putrescine, spermidine and
      spermine are ubiquitous in all living cells. Their indispensable roles in many
      biochemical and physiological processes are becoming commonly known, including
      promoters of plant life and differential roles in human health and disease. PAs
      positively impact cellular functions in plants-exemplified by increasing
      longevity, reviving physiological memory, enhancing carbon and nitrogen resource
      allocation/signaling, as well as in plant development and responses to extreme
      environments. Thus, one or more PAs are commonly found in genomic and
      metabolomics studies using plants, particulary during different abiotic stresses.
      In humans, a general decline in PA levels with aging occurs parallel with some
      human health disorders. Also, high PA dose is detrimental to patients suffering
      from cancer, aging, innate immunity and cognitive impairment during Alzheimer and
      Parkinson diseases. A dichotomy exists in that while PAs may increase longevity
      and reduce some age-associated cardiovascular diseases, in disease conditions
      involving higher cellular proliferation, their intake has negative consequences.
      Thus, it is essential that PA levels be rigorously quantified in edible plant
      sources as well as in dietary meats. Such a database can be a guide for medical
      experts in order to recommend which foods/meats a patient may consume and which
      ones to avoid. Accordingly, designing both high and low polyamine diets for human
      consumption are in vogue, particularly in medical conditions where PA intake may
      be detrimental, for instance, cancer patients. In this review, literature data
      has been collated for the levels of the three main PAs, putrescine, spermidine
      and spermine, in different edible sources-vegetables, fruits, cereals, nuts,
      meat, sea food, cheese, milk, and eggs. Based on our analysis of vast literature,
      the effects of PAs in human/animal health fall into two broad, Yang and Yin,
      categories: beneficial for the physiological processes in healthy cells and
      detrimental under pathological conditions.

PMID- 29468151
TI  - Combination of Virtual Screening Protocol by in Silico toward the Discovery of
      Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.
AB  - 4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is a potent new
      bleaching herbicide target. Therefore, in silico structure-based virtual
      screening was performed in order to speed up the identification of promising HPPD
      inhibitors. In this study, an integrated virtual screening protocol by combining
      3D-pharmacophore model, molecular docking and molecular dynamics (MD) simulation
      was established to find novel HPPD inhibitors from four commercial databases. 3D
      pharmacophore Hypo1 model was applied to efficiently narrow potential hits. The
      hit compounds were subsequently submitted to molecular docking studies, showing
      four compounds as potent inhibitor with the mechanism of the Fe(II) coordination
      and interaction with Phe360, Phe403, and Phe398. MD result demonstrated that
      nonpolar term of compound 3881 made great contributions to binding affinities. It
      showed an IC50 being 2.49 MUM against AtHPPD in vitro. The results provided
      useful information for developing novel HPPD inhibitors, leading to further
      understanding of the interaction mechanism of HPPD inhibitors.

PMID- 29468152
TI  - Negative Thermal Expansion over a Wide Temperature Range in Fe-Doped MnNiGe
      Composites.
AB  - Fe-doped MnNiGe alloys were successfully synthesized by solid-state reaction.
      Giant negative thermal expansion (NTE) behaviors with the coefficients of thermal
      expansion (CTE) of -285.23 * 10-6 K-1 (192-305 K) and -1167.09 * 10-6 K-1 (246
      305 K) have been obtained in Mn0.90Fe0.10NiGe and MnNi0.90Fe0.10Ge, respectively.
      Furthermore, these materials were combined with Cu in order to control the NTE
      properties. The results indicate that the absolute value of CTE gradually
      decreases with increasing Cu contents. In Mn0.92Fe0.08NiGe/x%Cu, the CTE
      gradually changes from -64.92 * 10-6 K-1 (125-274 K) to -4.73 * 10-6 K-1 (173-229
      K) with increasing value of x from 15 to 70. The magnetic measurements reveal
      that the NTE behaviors in this work are strongly correlated with the process of
      the magnetic phase transition and the introduction of Fe atoms could also change
      the spiral anti-ferromagnetic (s-AFM) state into ferromagnetic (FM) state at low
      temperature. Our study launches a new candidate for controlling thermal expansion
      properties of metal matrix materials which could have potential application in
      variable temperature environment.

PMID- 29468153
TI  - The Correlation of Adsorption Behavior between Ciprofloxacin Hydrochloride and
      the Active Sites of Fe-doped MCM-41.
AB  - HIGHLIGHTS Fe incorporation significantly accelerated the adsorption of CPX on
      MCM-41.Fe leaching can be ignored when pH was higher than 4.0.pH played an
      important role in CPX adsorption on Fe-MCM-41.Co-effect of CPX and metal cations
      on Fe-MCM-41 was investigated. Fe-MCM-41s with various molar ratios of silicon to
      iron (20, 40, 80, and 160) were prepared to investigate adsorption properties of
      ciprofloxacin hydrochloride (CPX) in aqueous solutions. Fe-MCM-41s were
      characterized by transmission electron microscope (TEM), X-ray diffraction (XRD),
      X-ray photoelectron spectroscopy (XPS), nitrogen adsorption/desorption isotherms,
      and infrared spectroscopy (FT-IR). Effects of silicon-iron ratio, adsorbent
      dosage, pH, and temperature were conducted to explore the adsorption mechanism of
      CPX on Fe-MCM-41. The results showed that the introduction of iron facilitated
      the absorption quantity for CPX from 20.04 to 83.33 mg g-1 at 120 min of reaction
      time, which was mainly attributed to surface complexation. The promotion of
      hydrophobic effect, electrostatic interactions, and pi-pi electron donor-acceptor
      interaction also played coordinate roles in the adsorption process. The
      experimental kinetic data followed both the pseudo-second-order and intra
      particle diffusion models, while the adsorption isotherm data fit well to
      Freundlich model at high temperature. Thermodynamic study showed that the
      adsorption was spontaneous. Under the effect of electrostatic interaction, pH of
      the solution strongly affected CPX adsorption. Five representative metal cations
      (Ca, Cu, Ni, Pb, and Cd) were chosen to study the effects on CPX adsorption and
      their complexation. The inhibiting effect of metal cations on CPX adsorption was
      sequenced in the order of Cu > Ni > Pb > Cd > Ca, which followed the same order
      as the complexation stability constants between CPX and cations. The Fe-MCM-41
      adsorbent possessed excellent reusability for 4 cycles use, suggesting a
      potential applicability of Fe-MCM-41 to remove CPX in water.

PMID- 29468154
TI  - Synthesis of Samarium-Cobalt Sub-micron Fibers and Their Excellent Hard Magnetic
      Properties.
AB  - High-throughput synthesis of Samarium-Cobalt sub-micron fibers with controlled
      composition and dimension was demonstrated by combining electrospinning and
      reduction-diffusion processes. The composition of fibers was readily varied (8 <
      Sm < 20 at.%) by adjusting precursor composition whereas the diameter of fibers
      was precisely controlled by varying electrospinning parameters (e.g., applied
      voltage, solution feed rate, temperature, and humidity) to reach single-domain
      size. X-ray diffraction patterns confirmed that single phase Sm2Co17 fibers were
      synthesized when the metal precursor ratio (Sm3+/(Sm3++Co2+)) was precisely
      controlled at 10.6%, whereas mixed phases (i.e., Co-Sm2Co17 or Sm2Co17-Sm2Co7)
      were observed when the ratio is deviated from the stoichiometric. Magnetic
      saturation (Ms ) of the synthesized fibers monotonically decreased with an
      increased in Sm content. In contrast, coercivity (Hci) monotonically increased
      with an increase in Sm content.

PMID- 29468155
TI  - A Low Cost Implantation Model in the Rat That Allows a Spatial Assessment of
      Angiogenesis.
AB  - There is continual demand for animal models that allow a quantitative assessment
      of angiogenic properties of biomaterials, therapies, and pharmaceuticals. In its
      simplest form, this is done by subcutaneous material implantation and subsequent
      vessel counting which usually omits spatial data. We have refined an implantation
      model and paired it with a computational analytic routine which outputs not only
      vessel count but also vessel density, distribution, and vessel penetration depth,
      that relies on a centric vessel as a reference point. We have successfully
      validated our model by characterizing the angiogenic potential of a fibrin matrix
      in conjunction with recombinant human vascular endothelial growth factor
      (rhVEGF165). The inferior epigastric vascular pedicles of rats were sheathed with
      silicone tubes, which were subsequently filled with 0.2 ml of fibrin and
      different doses of rhVEGF165, centrically embedding the vessels. Over 4 weeks,
      tissue samples were harvested and subsequently immunohistologically stained and
      computationally analyzed. The model was able to detect variations over the
      angiogenic potentials of growth factor spiked fibrin matrices. Adding 20 ng of
      rhVEGF165 resulted in a significant increase in vasculature while 200 ng of
      rhVEGF165 did not improve vascular growth. Vascularized tissue volume increased
      during the first week and vascular density increased during the second week.
      Total vessel count increased significantly and exhibited a peak after 2 weeks
      which was followed by a resorption of vasculature by week 4. In summary, a simple
      implantation model to study in vivo vascularization with only a minimal workload
      attached was enhanced to include morphologic data of the emerging vascular tree.

PMID- 29468156
TI  - Adherent vs. Free-Floating Neural Induction by Dual SMAD Inhibition for
      Neurosphere Cultures Derived from Human Induced Pluripotent Stem Cells.
AB  - Keeping neural stem cells under proliferation, followed by terminal
      differentiation, can substantially increase the number of neurons generated. With
      regard to the usability of proliferating neurospheres (NSPHs) cultures, adherent
      induction protocols have not yet been studied in comparison to embryoid body (EB)
      based protocols. To compare these proctocols, neural induction of human induced
      pluripotent stem cells was performed by dual SMAD inhibition under both adherent
      and free-floating EB culture conditions. After 10 days, we transferred cells to
      low-attachment culture plates and proliferated them as free-floating
      neurospheres. RNA was collected, transcribed to cDNA and analyzed for sonic
      hedgehog expression that plays an important role during proliferation process.
      NSPHs were analyzed by immunofluorescence imaging directly and upon continued
      differentiation. The EB-based approach yielded in higher numbers of cells
      expressing the neural stem cell marker Nestin, and showed in contrast to the
      adherent induction protocol increased expression levels of sonic hedgehog.
      Although improvements to culture consistency and reliability are desirable, the
      EB-based protocol appears to be superior to the adherent protocol for both, the
      proliferation and differentiation capacity.

PMID- 29468157
TI  - Dancing Styles of Collective Cell Migration: Image-Based Computational Analysis
      of JRAB/MICAL-L2.
AB  - Collective cell migration is observed during morphogenesis, angiogenesis, and
      wound healing, and this type of cell migration also contributes to efficient
      metastasis in some kinds of cancers. Because collectively migrating cells are
      much better organized than a random assemblage of individual cells, there seems
      to be a kind of order in migrating clusters. Extensive research has identified a
      large number of molecules involved in collective cell migration, and these
      factors have been analyzed using dramatic advances in imaging technology. To
      date, however, it remains unclear how myriad cells are integrated as a single
      unit. Recently, we observed unbalanced collective cell migrations that can be
      likened to either precision dancing or awa-odori, Japanese traditional dancing
      similar to the style at Rio Carnival, caused by the impairment of the
      conformational change of JRAB/MICAL-L2. This review begins with a brief history
      of image-based computational analyses on cell migration, explains why
      quantitative analysis of the stylization of collective cell behavior is
      difficult, and finally introduces our recent work on JRAB/MICAL-L2 as a
      successful example of the multidisciplinary approach combining cell biology, live
      imaging, and computational biology. In combination, these methods have enabled
      quantitative evaluations of the "dancing style" of collective cell migration.

PMID- 29468158
TI  - Central and Peripheral Nervous System Progenitors Derived from Human Pluripotent
      Stem Cells Reveal a Unique Temporal and Cell-Type Specific Expression of PMCAs.
AB  - The P-type ATPases family consists of ion and lipid transporters. Their unique
      diversity in function and expression is critical for normal development. In this
      study we investigated human pluripotent stem cells (hPSC) and different neural
      progenitor states to characterize the expression of the plasma membrane calcium
      ATPases (PMCAs) during human neural development and in mature mesencephalic
      dopaminergic (mesDA) neurons. Our RNA sequencing data identified a dynamic change
      in ATPase expression correlating with the differentiation time of the neural
      progenitors, which was independent of the neuronal progenitor type. Expression of
      ATP2B1 and ATP2B4 were the most abundantly expressed, in accordance with their
      main role in Ca2+ regulation and we observed all of the PMCAs to have a
      subcellular punctate localization. Interestingly in hPSCs ATP2B1 and ATP2B3 were
      highly expressed in a cell cycle specific manner and ATP2B2 and ATP2B4 were
      highly expressed in a hPSC sub-population. In neural rosettes a strong apical
      PMCA expression was identified in the luminal region. Lastly, we confirmed all
      PMCAs to be expressed in mesDA neurons, however at varying levels. Our results
      reveal that PMCA expression dynamically changes during stem cell differentiation
      and highlights the diverging needs of cell populations to regulate and properly
      integrate Ca2+ changes, which can ultimately correspond to changes in specific
      stem cell transcription states.

PMID- 29468159
TI  - IL-1beta Promotes a New Function of DNase I as a Transcription Factor for the Fas
      Receptor Gene.
AB  - Recently we described that endonuclease inactive DNase I translocated into the
      nucleus in response to increased endogenous IL-1beta expression. Here, we
      demonstrate impact and function of translocated DNase I in tubular cells. Effect
      of cytokines on expression level and nuclear localisation of DNase I and
      corresponding levels of Fas receptor (FasR) and IL-1beta were determined by
      confocal microscopy, qPCR and western blot analyses, in presence or absence of
      siRNA against IL-1beta and DNase I mRNA. Nuclear DNase I bound to the FAS
      promotor region as determined by chromatin immuno-precipitation analysis. Data
      demonstrate that; (i) translocation of DNase I depended on endogenous de novo
      expressed IL-1beta, (ii) nuclear DNase I bound FAS DNA, (iii) FasR expression
      increased after translocation of DNase I, (iv) interaction of exogenous Fas
      ligand (FasL) with upregulated FasR induced apoptosis in human tubular cells
      stimulated with TNFalpha. Thus, translocated DNase I most probably binds the
      promoter region of the FAS gene and function as a transcription factor for FasR.
      In conclusion, DNase I not only executes chromatin degradation during apoptosis
      and necrosis, but also primes the cells for apoptosis by enhancing FasR
      expression.

PMID- 29468161
TI  - Big Data and Dementia: Charting the Route Ahead for Research, Ethics, and Policy.
AB  - Emerging trends in pervasive computing and medical informatics are creating the
      possibility for large-scale collection, sharing, aggregation and analysis of
      unprecedented volumes of data, a phenomenon commonly known as big data. In this
      contribution, we review the existing scientific literature on big data approaches
      to dementia, as well as commercially available mobile-based applications in this
      domain. Our analysis suggests that big data approaches to dementia research and
      care hold promise for improving current preventive and predictive models, casting
      light on the etiology of the disease, enabling earlier diagnosis, optimizing
      resource allocation, and delivering more tailored treatments to patients with
      specific disease trajectories. Such promissory outlook, however, has not
      materialized yet, and raises a number of technical, scientific, ethical, and
      regulatory challenges. This paper provides an assessment of these challenges and
      charts the route ahead for research, ethics, and policy.

PMID- 29468160
TI  - Adhesion GPCRs in Kidney Development and Disease.
AB  - Chronic kidney disease (CKD) represents the fastest growing pathology worldwide
      with a prevalence of >10% in many countries. In addition, kidney cancer
      represents 5% of all new diagnosed cancers. As currently no effective therapies
      exist to restore kidney function after CKD- as well as cancer-induced renal
      damage, it is important to elucidate new regulators of kidney development and
      disease as new therapeutic targets. G protein-coupled receptors (GPCRs) represent
      the most successful class of pharmaceutical targets. In recent years adhesion
      GPCRs (aGPCRs), the second largest GPCR family, gained significant attention as
      they are present on almost all mammalian cells, are associated to a plethora of
      diseases and regulate important cellular processes. aGPCRs regulate for example
      cell polarity, mitotic spindle orientation, cell migration, and cell aggregation;
      all processes that play important roles in kidney development and/or disease.
      Moreover, polycystin-1, a major regulator of kidney development and disease,
      contains a GAIN domain, which is otherwise only found in aGPCRs. In this review,
      we assess the potential of aGPCRs as therapeutic targets for kidney disease. For
      this purpose we have summarized the available literature and analyzed data from
      the databases The Human Protein Atlas, EURExpress, Nephroseq, FireBrowse,
      cBioPortal for Cancer Genomics and the National Cancer Institute Genomic Data
      Commons data portal (NCIGDC). Our data indicate that most aGPCRs are expressed in
      different spatio-temporal patterns during kidney development and that altered
      aGPCR expression is associated with a variety of kidney diseases including CKD,
      diabetic nephropathy, lupus nephritis as well as renal cell carcinoma. We
      conclude that aGPCRs present a promising new class of therapeutic targets and/or
      might be useful as diagnostic markers in kidney disease.

PMID- 29468162
TI  - Short-term Oral Antibiotics Treatment Promotes Inflammatory Activation of Colonic
      Invariant Natural Killer T and Conventional CD4+ T Cells.
AB  - The gut mucosa is continuously exposed to a vast community of microorganisms,
      collectively defined as microbiota, establishing a mutualistic relationship with
      the host and contributing to shape the immune system. Gut microbiota is acquired
      at birth, and its composition is relatively stable during the entire adult life.
      Intestinal dysbiosis, defined as a microbial imbalance of gut bacterial
      communities, can be caused by several factors, including bacterial infections and
      antibiotic use, and has been associated with an increased risk to develop or
      exacerbate immune-mediated pathologies, such as allergic reactions, asthma, and
      inflammatory bowel diseases. Still, the mechanisms by which antibiotic-induced
      gut dysbiosis may lead to development of mucosal inflammation are still matter of
      debate. To this end, we aimed to evaluate the impact of antibiotic treatment on
      phenotype and functions of intestinal immune cell populations, including
      invariant natural killer T (iNKT) cells, a subset of lipid-specific T cells
      profoundly influenced by alterations on the commensal microbiota. To this aim, a
      cocktail of broad-spectrum antibiotics was administered for 2 weeks to otherwise
      healthy mice before re-colonization of the intestinal microbial community with
      oral gavage of eubiotic or dysbiotic mucosa-associated bacteria and luminal
      colonic content, followed or not by intestinal inflammation induction. Here. we
      showed that short-term antibiotic treatment alters frequency and functions of
      intestinal iNKT cells, even in the absence of intestinal inflammation. The
      presence of a dysbiotic microbiota after antibiotic treatment imprints colonic
      iNKT and CD4+ T cells toward a pro-inflammatory phenotype that collectively
      contributes to aggravate intestinal inflammation. Nonetheless, the inflammatory
      potential of the dysbiotic microbiota decreases over time opening the possibility
      to temporally intervene on the microbial composition to re-equilibrate dysbiosis,
      thus controlling concomitantly mucosal immune T cell activations.

PMID- 29468163
TI  - The Effect of Flaxseed in Breast Cancer: A Literature Review.
AB  - Breast cancer is one of the most common cancers and the second most responsible
      for cancer mortality worldwide. In 2014, in Portugal approximately 27,200 people
      died of cancer, of which 1,791 were women with breast cancer. Flaxseed has been
      one of the most studied foods, regarding possible relations to breast cancer,
      though mainly in experimental studies in animals, yet in few clinical trials. It
      is rich in omega-3 fatty acids, alpha-linolenic acid, lignan, and fibers. One of
      the main components of flaxseed is the lignans, of which 95% are made of the
      predominant secoisolariciresinol diglucoside (SDG). SDG is converted into
      enterolactone and enterodiol, both with antiestrogen activity and structurally
      similar to estrogen; they can bind to cell receptors, decreasing cell growth.
      Some studies have shown that the intake of omega-3 fatty acids is related to the
      reduction of breast cancer risk. In animal studies, alpha-linolenic acids have
      been shown to be able to suppress growth, size, and proliferation of cancer cells
      and also to promote breast cancer cell death. Other animal studies found that the
      intake of flaxseed combined with tamoxifen can reduce tumor size to a greater
      extent than taking tamoxifen alone. Additionally, some clinical trials showed
      that flaxseed can have an important role in decreasing breast cancer risk, mainly
      in postmenopausal women. Further studies are needed, specifically clinical trials
      that may demonstrate the potential benefits of flaxseed in breast cancer.

PMID- 29468164
TI  - Glutamine Hydrolysis by Imidazole Glycerol Phosphate Synthase Displays
      Temperature Dependent Allosteric Activation.
AB  - The enzyme imidazole glycerol phosphate synthase (IGPS) is a model for studies of
      long-range allosteric regulation in enzymes. Binding of the allosteric effector
      ligand N'-[5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamide
      ribonucleotide (PRFAR) stimulates millisecond (ms) timescale motions in IGPS that
      enhance its catalytic function. We studied the effect of temperature on these
      critical conformational motions and the catalytic mechanism of IGPS from the
      hyperthermophile Thermatoga maritima in an effort to understand temperature
      dependent allostery. Enzyme kinetic and NMR dynamics measurements show that apo
      and PRFAR-activated IGPS respond differently to changes in temperature. Multiple
      quantum Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments
      performed at 303, 323, and 343 K (30, 50, and 70 degrees C) reveal that
      millisecond flexibility is enhanced to a higher degree in apo IGPS than in the
      PRFAR-bound enzyme as the sample temperature is raised. We find that the
      flexibility of the apo enzyme is nearly identical to that of its PRFAR activated
      state at 343 K, whereas conformational motions are considerably different between
      these two forms of the enzyme at room temperature. Arrhenius analyses of these
      flexible sites show a varied range of activation energies that loosely correlate
      to allosteric communities identified by computational methods and reflect local
      changes in dynamics that may facilitate conformational sampling of the active
      conformation. In addition, kinetic assays indicate that allosteric activation by
      PRFAR decreases to 65-fold at 343 K, compared to 4,200-fold at 303 K, which
      mirrors the decreased effect of PRFAR on ms motions relative to the unactivated
      enzyme. These studies indicate that at the growth temperature of T. maritima,
      PFRAR is a weaker allosteric activator than it is at room temperature and
      illustrate that the allosteric mechanism of IGPS is temperature dependent.

PMID- 29468165
TI  - A Review of African Swine Fever and the Potential for Introduction into the
      United States and the Possibility of Subsequent Establishment in Feral Swine and
      Native Ticks.
AB  - African swine fever (ASF) is caused by African swine fever virus (ASFV), which
      can cause substantial morbidity and mortality events in swine. The virus can be
      transmitted via direct and indirect contacts with infected swine, their products,
      or competent vector species, especially Ornithodoros ticks. Africa and much of
      Eastern Europe are endemic for ASF; a viral introduction to countries that are
      currently ASF free could have severe economic consequences due to the loss of
      production from infected animals and the trade restrictions that would likely be
      imposed as a result of an outbreak. We identified vulnerabilities that could lead
      to ASFV introduction or persistence in the United States or other ASF-free
      regions. Both legal and illegal movements of live animals, as well as the
      importation of animal products, byproducts, and animal feed, pose a risk of virus
      introduction. Each route is described, and current regulations designed to
      prevent ASFV and other pathogens from entering the United States are outlined.
      Furthermore, existing ASFV research gaps are highlighted. Laboratory experiments
      to evaluate multiple species of Ornithodoros ticks that have yet to be
      characterized would be useful to understand vector competence, host preferences,
      and distribution of competent soft tick vectors in relation to high pig
      production areas as well as regions with high feral swine (wild boar or similar)
      densities. Knowledge relative to antigenic viral proteins that contribute to host
      response and determination of immune mechanisms that lead to protection are
      foundational in the quest for a vaccine. Finally, sampling of illegally imported
      and confiscated wild suid products for ASFV could shed light on the types of
      products being imported and provide a more informed perspective relative to the
      risk of ASFV importation.

PMID- 29468166
TI  - Suspicion of Postanesthetic Femoral Paralysis of the Non-Dependent Limb in a
      Horse.
AB  - A 15-year-old Selle Francais gelding was presented to the equine referral
      hospital for treatment of a left guttural pouch mycosis previously diagnosed.
      After induction, the horse was shortly hoisted by all four feet, moved on a
      padded surgical table, and positioned in right lateral recumbency. In order to
      reduce the risk of bleeding during surgical manipulation of the carotid and
      maxillary arteries, a mean arterial pressure between 60 and 70 mmHg was targeted.
      After surgery, the horse was moved in a padded recovery box keeping the same
      lateral recumbency. Four unsuccessful attempts were performed, with the horse
      always returning to sternal recumbency keeping the left hind limb up. At the
      fifth attempt, performed 120 min after the end of the general anesthesia, the
      horse stood up correctly but moderate ataxia and absence of weight bearing on the
      left hind limb were shown. Both the stifle and the fetlock joint were held in a
      flexed position and could not be extended properly in order to set the foot on
      the ground, resulting in a very short step. The horse was calm, not sweating, and
      willing to move; the muscles of the affected limb were relaxed, and the limb was
      neither warm nor painful at palpation. Occasionally, the horse flexed the
      affected hind limb in an exaggerated motion with marked abduction. No additional
      laboratory analyses were performed. Due to a strong suspicion of neuropathy, a
      sling support was initiated and a supportive bandage associated with flunixine
      administration was performed until resolution of the symptoms. The horse fully
      recovered after 3 days. This case report does not clarify the pathogenesis of the
      possible postanesthetic neuropathy accounted on the non-dependent limb,
      highlighting the need for future research in this field. Non-dependent limb
      neuropathy should be an expected problem even after having ruled out the most
      commonly known causes predisposing to postanesthetic lameness.

PMID- 29468167
TI  - Fatal fulminant herpes simplex hepatitis following surgery in an adult.
AB  - We present a case of a healthy 72-year-old man with herpes simplex hepatitis
      (HSVH) development soon after ordinary surgery for biliary stones. A sudden onset
      of hepatitis associated with high fever and leukopenia emerged on postoperative
      day 5, followed by a rapid and lethal course (died on day 9), despite an
      acyclovir therapy on day 8. Postmortem liver biopsy revealed positive
      immunostaining for herpes simplex virus (HSV) type-1. The serum tests (available
      after the death) were negative for anti-HSV immunogloblulins, but positive for
      HSV DNA. A review of 15 cases of postsurgical HSVH along with 42 cases of non
      surgical HSH showed that (1): A wide spectrum of surgical procedures was
      involved; and (2): High mortality (87%) associated with lower rates of ante
      mortem diagnosis (20%) and acyclovir treatment (20%). Due to the difficulty in
      diagnosis and lethal nature, an early clinical suspension and prompt empirical
      anti-viral intervention are imperative for postsurgical hepatitis with
      undetermined etiology, characterized by fever and leucopenia.

PMID- 29468168
TI  - Severe Pulmonary Hypertension Due to Adult-Onset Still's Disease.
AB  - A 29-year-old female with adult-onset Still's disease (AOSD) presented with
      progressive shortness of breath both on rest and on exertion, increased abdominal
      girth, and swelling in both legs. She was on oral prednisone and was recently
      started on canakinumab (interleukin-1 antagonist) for joint pain and rash of
      AOSD. Echocardiogram showed severely dilated right ventricle, dilated pulmonary
      artery, moderately reduced right ventricular systolic function, but with normal
      left ventricular systolic function. Computed tomography with contrast ruled out
      pulmonary embolism. Blood tests ruled out other rheumatologic diseases. The
      patient was diagnosed with right-sided heart failure likely secondary to AOSD.
      Right heart catheterization was needed but could not be performed because of
      severely dilated pulmonary artery. The patient was transferred to a higher center
      for further management and possible cardiopulmonary transplant.

PMID- 29468169
TI  - Severe Human Granulocytic Anaplasmosis With Significantly Elevated Ferritin
      Levels in an Immunocompetent Host in Pennsylvania: A Case Report.
AB  - Human granulocytic anaplasmosis (HGA) is a tick-borne, infectious disease caused
      by Anaplasma phagocytophilum that generally presents with nonspecific symptoms
      such as fever, chills, headache, malaise, and myalgia. If not treated
      immediately, HGA can cause hemophagocytic lymphohistiocytosis (HLH), a well
      documented but underrecognized sequela of severe HGA. In this article, we report
      a case of severe HGA with hyperferritinemia in a 74-year-old male from Central
      Pennsylvania who initially presented with recurrent fevers, nausea, and malaise
      to our emergency department and was subsequently discharged home that same day.
      Ten days later, the patient returned with acute kidney injury, elevated liver
      transaminases, and profound hyperferritinemia to 5130 ng/mL. Empiric doxycycline
      was administered for suspected tick-borne disease and serologies eventually came
      back positive for anti-Anaplasma phagocytophilum antibodies. The patient returned
      to baseline status 15 days after discharge. Our case shows the challenges in the
      timely diagnosis of HGA and highlights the role of serum ferritin in aiding this
      diagnosis. Although our patient did not fulfill the HLH diagnostic criteria, our
      report demonstrates the importance of recognizing HGA as a reversible cause of
      HLH.

PMID- 29468170
TI  - Hyoid Dislocation Following Subacute Fracture in an American High School Football
      Athlete.

PMID- 29468171
TI  - Influence of Meniscal and Chondral Lesions on Patient-Reported Outcomes After
      Primary Anterior Cruciate Ligament Reconstruction at 2-Year Follow-up.
AB  - Background: Meniscal and chondral lesions are commonly associated with anterior
      cruciate ligament (ACL) tears, and these lesions may play a role in patient
      outcomes after ACL reconstruction. Purpose: To determine the effects of the
      presence and location of meniscal and chondral lesions at the time of ACL
      reconstruction on patient-reported outcomes at a minimum 2-year follow-up. Study
      Design: Cohort study; Level of evidence, 3. Methods: Patients with no prior knee
      surgery who underwent primary ACL reconstruction by a single surgeon between 2010
      and 2014 were included in this study. Those meeting inclusion criteria were
      divided into the following groups based on the arthroscopic diagnosis: patients
      without concomitant meniscal or chondral lesions, patients with isolated meniscal
      lesions, patients with isolated chondral lesions, and patients with both chondral
      and meniscal lesions. Patient-reported outcomes (Short Form-12 [SF-12] physical
      component summary [PCS] and mental component summary [MCS], Western Ontario and
      McMaster Universities Osteoarthritis Index [WOMAC], and Lysholm scale) were
      assessed at a minimum of 2 years from the index surgery. Results: A total of 151
      patients met the inclusion criteria and were included in the study. The mean age
      at the time of surgery was 36.2 years (range, 14-73 years), and the mean follow
      up was 3.2 years (range, 2.0-5.6 years). At the time of surgery, 33 (22%)
      patients had no concomitant lesions and served as the control group, 63 (42%)
      patients had isolated meniscal lesions, 21 (14%) patients had isolated chondral
      lesions, and 34 (22%) patients had both chondral and meniscal lesions. There was
      significant improvement in all outcome scores postoperatively for the 3 groups (P
      < .05 for all outcome scores). The presence of a meniscal tear and laterality of
      the meniscal lesion did not have a negative effect on any postoperative outcome
      scores. Patients with isolated chondral lesions had significantly lower
      postoperative WOMAC scores compared with patients without chondral lesions (P <
      .05). No significant differences were found for all other scores. Patients with
      patellofemoral chondral lesions had significantly lower postoperative SF-12 PCS
      and Lysholm scores than patients with tibiofemoral chondral lesions (P < .05).
      Conclusion: Patients with ACL tears achieved improved functional scores at a mean
      3.2 years after ACL reconstruction. While meniscal lesions did not affect
      postoperative outcomes in the short term, chondral lesions were identified as a
      predictor for worse outcomes.

PMID- 29468172
TI  - Hip Arthroscopic Surgery for Femoroacetabular Impingement: A Prospective Analysis
      of the Relationship Between Surgeon Experience and Patient Outcomes.
AB  - Background: Hip arthroscopic surgery is a rapidly growing procedure, but it may
      be associated with a steep learning curve. Few studies have used patient-reported
      outcome (PRO) surveys to investigate the relationship between surgeon experience
      and patient outcomes after the arthroscopic treatment of femoroacetabular
      impingement (FAI). Hypothesis: Patients undergoing hip arthroscopic surgery for
      the treatment of FAI in the early stages of a surgeon's career will have
      significantly worse outcomes and longer procedure times compared with patients
      treated after the surgeon has gained experience. Study Design: Cohort study;
      Level of evidence, 2. Methods: Patients undergoing hip arthroscopic surgery for
      FAI and labral injuries were prospectively enrolled during a sports medicine
      fellowship-trained surgeon's first 15 months of practice. Patients were
      stratified into an early group, consisting of the first 30 consecutive cases
      performed by the surgeon, and a late group, consisting of the second 30
      consecutive cases. Radiographic and physical examinations were performed
      preoperatively and postoperatively. PRO surveys, including the 12-item Short Form
      Health Survey (SF-12), the modified Harris Hip Score (mHHS), and the Hip
      disability and Osteoarthritis Outcome Score (HOOS), were administered
      preoperatively and at a minimum of 1 year postoperatively. Results: There was no
      difference between the early and late groups for patient age (37.2 +/- 11.5 vs
      35.3 +/- 10.8 years, respectively; P = .489), body mass index (25.6 +/- 4.0 vs
      25.1 +/- 4.5 kg/m2, respectively; P = .615), or sex (P = .465). There was a
      significantly increased procedure time (119.3 +/- 21.0 vs 99.0 +/- 28.6 minutes,
      respectively; P = .002) and traction time (72.7 +/- 21.4 vs 59.0 +/- 16.7
      minutes, respectively; P = .007) in the early group compared with the late group.
      Mean postoperative PRO scores significantly improved in both groups compared with
      preoperative values for all surveys except for the SF-12 mental component
      summary. No differences were found in PRO score improvements or complication
      rates between the early and late groups. Conclusion: The total procedure time and
      traction time decrease after a surgeon's first 30 hip arthroscopic surgery cases
      for FAI and labral tears, but patient outcomes can similarly improve regardless
      of surgeon experience in the early part of his or her career.

PMID- 29468173
TI  - Effect of desipramine on patients with breathing disorders in RETT syndrome.
AB  - Objective: Rett Syndrome (RTT) is a severe neurodevelopmental condition with
      breathing disorders, affecting around one in 10,000 female births. Desipramine, a
      noradrenaline reuptake inhibitor, reduced the number of apneas in Mecp2-deficient
      mice, a model of RTT. We planned a phase 2 trial to test its efficacy and its
      safety on breathing patterns in 36 girls with RTT. Methods: The trial was a 6
      month, multicenter, randomized, double-blind, placebo-controlled study registered
      with ClinicalTrials.gov, number NCT00990691. Girls diagnosed according to
      clinical examination and confirmed by genotyping were randomly assigned in a
      1:1:1 ratio to receive 2-3 mg/kg Desipramine per day (high Desipramine), 1-2
      mg/kg Desipramine per day (low Desipramine), or a placebo. The primary outcome
      was the change of apnea hypopnea index (AHI), defined by the number of apnea and
      hypopnea events per hour, assessed at 6 months from baseline. Intention-to-treat
      analysis was applied. Results: The median change in AHI from baseline to 6 months
      was -31 (IQR: -37 to -11) for the high Desipramine, -17.5 (IQR: -31 to 13) for
      the low Desipramine, and -13 (IQR:-31 to 0) for the placebo group. We did not
      find any significant difference in these changes between the groups (P = 0.781).
      A significant inverse correlation between Desipramine plasma concentration and
      AHI (r = -0.44; P = 0.0002) was underlined. Interpretation: This first clinical
      trial of desipramine did not show clinical efficacy. Although required further
      studies, the significant correlation between Desipramine concentrations and
      improvement of AHI provided additional and relevant reasons to test the
      noradrenergic pathway in RTT.

PMID- 29468174
TI  - Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2.
AB  - Objective: Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly
      inherited neurodegenerative disease mainly affecting the cerebellum and
      brainstem. In this Cuban-German research collaboration, we aimed to characterize
      atrophy patterns and associations with clinical measures in preclinical and
      manifest SCA2. Methods: In this study, 16 nonmanifest SCA2 mutation carriers, 26
      manifest patients with SCA2, and 18 healthy control subjects underwent magnetic
      resonance imaging, as well as genetic and clinical characterization including
      assessment of ataxia (Scale for the Assessment and Rating of Ataxia) and saccade
      velocity in Cuba were enrolled. Semiautomated quantitative volumetry of the
      cerebellum and brainstem, subdivided into the medulla oblongata, the pontine
      brainstem, and mesencephalon was performed. Additionally, the anteroposterior
      diameter of the pontine brainstem was measured. Results: Analysis of volumetric
      data revealed degeneration of the cerebellum and brainstem, in particular of
      pontine volumes and the anteroposterior diameter of the pons, in both manifest
      SCA2 patients and individuals at risk for SCA2 compared to controls. Comparing
      patients with nonataxic preclinical SCA2 mutation carriers, we found more
      pronounced reductions of the pontine brainstem and cerebellum in manifest SCA2.
      Volumetric data further showed associations with CAG repeat length and predicted
      age of onset in preclinical SCA2 individuals, and by trend with ataxia signs in
      patients. Although saccade velocity was associated with reduction in the pontine
      brainstem in preclinical and manifest SCA2, reduced ability to suppress
      interfering stimuli measured by the Stroop task was related to cerebellar volume
      loss in patients. Interpretation: Preclinical SCA2 mutation carriers exhibit
      brain abnormalities, which could be targeted as surrogate parameters for disease
      progression and in future preventive trials.

PMID- 29468175
TI  - Rapamycin prevents cerebral stroke by modulating apoptosis and autophagy in
      penumbra in rats.
AB  - Objective: Whether activation or inhibition of the mTOR pathway is beneficial to
      ischemic injury remains controversial. It may result from the different reaction
      of ischemic penumbra and core to modulation of mTOR pathway after cerebral
      ischemia-reperfusion injury in rats. Methods: Longa's middle cerebral artery
      occlusion (MCAO) method was conducted to induce the focal cerebral ischemia
      reperfusion. Western blot analysis was used to examine the protein expression
      involving mTOR pathway, apoptosis, and autophagy-related proteins. TTC staining
      and Fluoro-Jade B staining was conducted to detect the infarct volume and cell
      apoptosis, respectively. Neurological function was measured by modified
      neurological severity score and left-biased swing. Results: mTOR signaling
      pathway was activated in ischemic penumbra and decreased in ischemic core after
      ischemia and ischemia-reperfusion. Ischemia-reperfusion injury induced the
      increase in cleaved caspase 9 and caspase 3 both in ischemic penumbra and in
      ischemic core, whereas the expression of phosphorylated ULK1, Beclin 1 and LC3-II
      was decreased. Rapamycin pre or postadministration inhibited the overactivation
      of mTOR pathway in ischemic penumbra. Ameliorated neurological function and
      reduced infarct volume were observed after pre or postrapamycin treatment.
      Rapamycin markedly decreased the number of FJB-positive cells and the expression
      of cleaved caspase-3 and cleaved caspase-9 proteins as well as increased the
      activation of autophagy reflected by ULK1, Beclin-1 and LC3. Interpretation: mTOR
      signaling pathway was activated in ischemic penumbra after cerebral ischemia
      reperfusion injury in rats. mTOR inhibitor rapamycin significantly decreased the
      mTOR activation and infarct volume and subsequently improved neurological
      function. These results may relate to inhibition of neuron apoptosis and
      activation of autophagy.

PMID- 29468176
TI  - Inhibition of the potassium channel Kv1.3 reduces infarction and inflammation in
      ischemic stroke.
AB  - Objective: Inhibitors of the voltage-gated K+ channel Kv1.3 are currently in
      development as immunomodulators for the treatment of autoimmune diseases. As
      Kv1.3 is also expressed on microglia and has been shown to be specifically up
      regulated on "M1-like" microglia, we here tested the therapeutic hypothesis that
      the brain-penetrant small-molecule Kv1.3-inhibitor PAP-1 reduces secondary
      inflammatory damage after ischemia/reperfusion. Methods: We studied microglial
      Kv1.3 expression using electrophysiology and immunohistochemistry, and evaluated
      PAP-1 in hypoxia-exposed organotypic hippocampal slices and in middle cerebral
      artery occlusion (MCAO) with 8 days of reperfusion in both adult male C57BL/6J
      mice (60 min MCAO) and adult male Wistar rats (90 min MCAO). In both models, PAP
      1 administration was started 12 h after reperfusion. Results: We observed Kv1.3
      staining on activated microglia in ischemic infarcts in mice, rats, and humans
      and found higher Kv1.3 current densities in acutely isolated microglia from the
      infarcted hemisphere than in microglia isolated from the contralateral hemisphere
      of MCAO mice. PAP-1 reduced microglia activation and increased neuronal survival
      in hypoxia-exposed hippocampal slices as effectively as minocycline. In mouse
      MCAO, PAP-1 dose-dependently reduced infarct area, improved neurological deficit
      score, and reduced brain levels of IL-1beta and IFN-gamma without affecting IL-10
      and brain-derived nerve growth factor (BDNF) levels or inhibiting ongoing
      phagocytosis. The beneficial effects on infarct area and neurological deficit
      score were reproduced in rats providing confirmation in a second species.
      Interpretation: Our findings suggest that Kv1.3 constitutes a promising
      therapeutic target for preferentially inhibiting "M1-like" inflammatory
      microglia/macrophage functions in ischemic stroke.

PMID- 29468177
TI  - CSF neurogranin or tau distinguish typical and atypical Alzheimer disease.
AB  - Objective: To assess whether high levels of cerebrospinal fluid neurogranin are
      found in atypical as well as typical Alzheimer's disease. Methods: Immunoassays
      were used to measure cerebrospinal fluid neurogranin in 114 participants
      including healthy controls (n = 27), biomarker-proven amnestic Alzheimer's
      disease (n = 68), and the atypical visual variant of Alzheimer's (n = 19)
      according to international criteria. CSF total-tau, Abeta42, and neurofilament
      light concentrations were investigated using commercially available assays. All
      affected individuals had T1-weighted volumetric MR images available for analysis
      of whole and regional brain volumes. Associations between neurogranin, brain
      volumes, total-tau, Abeta42, and neurofilament light were assessed. Results:
      Median cerebrospinal fluid neurogranin concentrations were higher in typical and
      atypical Alzheimer's compared to controls (P < 0.001 and P = 0.005). Both
      neurogranin and total-tau concentrations, but not neurofilament light and
      Abeta42, were higher in typical Alzheimer's compared to atypical patients (P =
      0.004 and P = 0.03). There were significant differences in the left hippocampus
      and right and left superior parietal lobules in atypical patients, which were
      larger (P = 0.03) and smaller (P = 0.001 and P < 0.001), respectively, compared
      to typical patients. We found no evidence of associations between neurogranin and
      brain volumes but a strong association with total-tau (P < 0.001) and a weaker
      association with neurofilament light (P = 0.005). Interpretation: These results
      show significant differences in neurogranin and total-tau between typical and
      atypical patients, which may relate to factors other than disease topography. The
      differential relationships between neurogranin, total-tau and neurofilament light
      in the Alzheimer's variants, provide evidence for mechanistically distinct and
      coupled markers of neurodegeneration.

PMID- 29468178
TI  - Retrograde interferon-gamma signaling induces major histocompatibility class I
      expression in human-induced pluripotent stem cell-derived neurons.
AB  - Objective: Injury-associated axon-intrinsic signals are thought to underlie
      pathogenesis and progression in many neuroinflammatory and neurodegenerative
      diseases, including multiple sclerosis (MS). Retrograde interferon gamma (IFN
      gamma) signals are known to induce expression of major histocompatibility class I
      (MHC I) genes in murine axons, thereby increasing the susceptibility of these
      axons to attack by antigen-specific CD8+ T cells. We sought to determine whether
      the same is true in human neurons. Methods: A novel microisolation chamber design
      was used to physically isolate and manipulate axons from human skin fibroblast
      derived induced pluripotent stem cell (iPSC)-derived neuron-enriched neural
      aggregates. Fluorescent retrobeads were used to assess the fraction of neurons
      with projections to the distal chamber. Axons were treated with IFN gamma for 72
      h and expression of MHC class I and antigen presentation genes were evaluated by
      RT-PCR and immunofluorescence. Results: Human iPSC-derived neural stem cells
      maintained as 3D aggregate cultures in the cell body chamber of polymer
      microisolation chambers extended dense axonal projections into the fluidically
      isolated distal chamber. Treatment of these axons with IFN gamma resulted in
      upregulation of MHC class I and antigen processing genes in the neuron cell
      bodies. IFN gamma-induced MHC class I molecules were also anterogradely
      transported into the distal axon. Interpretation: These results provide
      conclusive evidence that human axons are competent to express MHC class I
      molecules, suggesting that inflammatory factors enriched in demyelinated lesions
      may render axons vulnerable to attack by autoreactive CD8+ T cells in patients
      with MS. Future work will be aimed at identifying pathogenic anti-axonal T cells
      in these patients.

PMID- 29468179
TI  - Cell transplantation strategies for acquired and inherited disorders of
      peripheral myelin.
AB  - Objective: To investigate transplantation of rat Schwann cells or human iPSC
      derived neural crest cells and derivatives into models of acquired and inherited
      peripheral myelin damage. Methods: Primary cultured rat Schwann cells labeled
      with a fluorescent protein for monitoring at various times after transplantation.
      Human-induced pluripotent stem cells (iPSCs) were differentiated into neural
      crest stem cells, and subsequently toward a Schwann cell lineage via two
      different protocols. Cell types were characterized using flow cytometry,
      immunocytochemistry, and transcriptomics. Rat Schwann cells and human iPSC
      derivatives were transplanted into (1) nude rats pretreated with lysolecithin to
      induce demyelination or (2) a transgenic rat model of dysmyelination due to PMP22
      overexpression. Results: Rat Schwann cells transplanted into sciatic nerves with
      either toxic demyelination or genetic dysmyelination engrafted successfully, and
      migrated longitudinally for relatively long distances, with more limited axial
      migration. Transplanted Schwann cells engaged existing axons and displaced
      dysfunctional Schwann cells to form normal-appearing myelin. Human iPSC-derived
      neural crest stem cells and their derivatives shared similar engraftment and
      migration characteristics to rat Schwann cells after transplantation, but did not
      further differentiate into Schwann cells or form myelin. Interpretation: These
      results indicate that cultured Schwann cells surgically delivered to peripheral
      nerve can engraft and form myelin in either acquired or inherited myelin injury,
      as proof of concept for pursuing cell therapy for diseases of peripheral nerve.
      However, lack of reliable technology for generating human iPSC-derived Schwann
      cells for transplantation therapy remains a barrier in the field.

PMID- 29468180
TI  - Is seizure frequency variance a predictable quantity?
AB  - Background: There is currently no formal method for predicting the range expected
      in an individual's seizure counts. Having access to such a prediction would be of
      benefit for developing more efficient clinical trials, but also for improving
      clinical care in the outpatient setting. Methods: Using three independently
      collected patient diary datasets, we explored the predictability of seizure
      frequency. Three independent seizure diary databases were explored:
      SeizureTracker (n = 3016), Human Epilepsy Project (n = 93), and NeuroVista (n =
      15). First, the relationship between mean and standard deviation in seizure
      frequency was assessed. Using that relationship, a prediction for the range of
      possible seizure frequencies was compared with a traditional prediction scheme
      commonly used in clinical trials. A validation dataset was obtained from a
      separate data export of SeizureTracker to further verify the predictions.
      Results: A consistent mathematical relationship was observed across datasets. The
      logarithm of the average seizure count was linearly related to the logarithm of
      the standard deviation with a high correlation (R2 > 0.83). The three datasets
      showed high predictive accuracy for this log-log relationship of 94%, compared
      with a predictive accuracy of 77% for a traditional prediction scheme. The
      independent validation set showed that the log-log predicted 94% of the correct
      ranges while the RR50 predicted 77%. Conclusion: Reliably predicting seizure
      frequency variability is straightforward based on knowledge of mean seizure
      frequency, across several datasets. With further study, this may help to increase
      the power of RCTs, and guide clinical practice.

PMID- 29468181
TI  - Seizure semiology: an important clinical clue to the diagnosis of autoimmune
      epilepsy.
AB  - Objective: The purpose of this study is to analyze the seizure semiologic
      characteristics of patients with autoimmune epilepsy (AE) and describe the
      investigation characteristics of AE using a larger sample size. Methods: This
      observational retrospective case series study was conducted from a tertiary
      epilepsy center between May 2014 and March 2017. Cases of new-onset seizures were
      selected based on laboratory evidence of autoimmunity. At the same time, typical
      mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS)
      were recruited as the control group from the subjects who underwent presurgical
      evaluation during the same period. Results: A total of 61 patients with AE were
      identified. Specific autoimmune antibodies were detected in 39 patients (63.93%),
      including anti-VGKC in 23 patients (37.70%), anti-NMDA-R in 9 patients (14.75%),
      anti-GABAB-R in 6 patients (9.84%), and anti-amphiphysin in 1 patient (1.64%).
      Regarding the seizure semiology, no significant differences were noted between AE
      patients with autoantibody and patients with suspected AE without antibody.
      Compared to typical MTLE patients with HS, both AE patients with autoantibody and
      patients with suspected AE without antibody had the same seizure semiologic
      characteristics, including more frequent SPS or CPS, shorter seizure duration,
      rare postictal confusion, and common sleeping SGTC seizures. Significance: This
      study highlights important seizure semiologic characteristics of AE. Patients
      with autoimmune epilepsy had special seizure semiologic characteristics. For
      patients with autoimmune epilepsy presenting with new-onset seizures in isolation
      or with a seizure-predominant neurological disorder, the special seizure
      semiologic characteristics may remind us to test neuronal nuclear/cytoplasmic
      antibodies early and initiate immunomodulatory therapies as soon as possible.
      Furthermore, the absence of neural-specific autoantibodies does not rule out AE.

PMID- 29468182
TI  - GLS loss of function causes autosomal recessive spastic ataxia and optic atrophy.
AB  - We describe a consanguineous family in which two brothers were affected by
      childhood onset spastic ataxia with optic atrophy and loss of motor and language
      skills. Through a combination of homozygosity mapping and whole-genome
      sequencing, we identified a homozygous copy number variant in GLS as the cause.
      The duplication leads to complete knockout of GLS expression. GLS encodes the
      brain- and kidney-specific enzyme glutaminase, which hydrolyzes glutamine for the
      production of glutamate, the most abundant central nervous system
      neurotransmitter. This is the first report implicating GLS loss of function in
      human disease.

PMID- 29468183
TI  - Charcot Marie Tooth disease type 4J with complex central nervous system features.
AB  - We describe a family with Charcot Marie Tooth disease type 4J presenting with
      features of Charcot Marie Tooth disease plus parkinsonism and aphemia. Genetic
      testing found two variants in the FIG4 gene: c.122T>C (p.I41T) - the most common
      Charcot Marie Tooth disease type 4J variant - and c.1949-10T>G (intronic).
      Proband fibroblasts showed absent FIG4 protein on western blot, and skipping of
      exon 18 by RT-PCR. As most patients with Charcot Marie Tooth disease type 4J do
      not have central nervous system deficits, we postulate the intronic variant and
      I41T mutation together are causing loss of FIG4 protein and subsequently the
      central nervous system findings in our family.

PMID- 29468185
TI  - In vitro and in vivo Limiting Dilution Assay for Colorectal Cancer.
AB  - The in vitro limiting dilution assay is used to determine the colorectal cancer
      initiating cell (CC-IC) frequency of a CC-IC enriched suspension culture, grown
      in growth factor enriched serum free media. The in vivo limiting dilution assay
      is used to determine the colorectal cancer initiating cell frequency of a primary
      colorectal cancer sample or an established suspension cell line using
      immunocompromised murine xenograft models. In vitro and vivo limiting dilution
      assays (LDAs) can be used to determine the effect of a specific treatment or
      genetic knockdown strategy on the initiating cell frequency of a population of CC
      ICs or colorectal cancer sample, respectively.

PMID- 29468184
TI  - Translational potential of human brain organoids.
AB  - The recent technology of 3D cultures of cellular aggregates derived from human
      stem cells have led to the emergence of tissue-like structures of various organs
      including the brain. Brain organoids bear molecular and structural resemblance
      with developing human brains, and have been demonstrated to recapitulate several
      physiological and pathological functions of the brain. Here we provide an
      overview of the development of brain organoids for the clinical community,
      focusing on the current status of the field with an critical evaluation of its
      translational value.

PMID- 29468186
TI  - Repetitive Questioning II.
AB  - Repetitive questioning is a major problem for caregivers, particularly taxing if
      they are unable to recognize and understand the reasons why their loved one keeps
      asking the same question over and over again. Caregivers may be tempted to
      believe that the patient does not even try to remember the answer given or is
      just getting obnoxious. This is incorrect. Repetitive questioning is due to the
      underlying disease: The patient's short term memory is impaired and he is unable
      to register, encode, retain and retrieve the answer. If he is concerned about a
      particular topic, he will keep asking the same question over and over again. To
      the patient each time she asks the question, it is as if she asked it for the
      first time. Just answering repetitive questioning by providing repeatedly the
      same answer is not sufficient. Caregivers should try to identify the underlying
      cause for this repetitive questioning. In an earlier case study, the patient was
      concerned about her and her family's safety and kept asking whether the doors are
      locked. In this present case study, the patient does not know how to handle the
      awkward situation he finds himself in. He just does not know what to do. He is
      not able to adjust to the new unexpected situation. So he repeatedly wants to
      reassure himself that he is not intruding by asking the same question over and
      over again. We discuss how the patient's son-in-law could have avoided this
      situation and averted the catastrophic ending.

PMID- 29468187
TI  - Sociodemographic Factors and Health-Related Characteristics That Influence the
      Quality of Life of Grandparent Caregivers in Zimbabwe.
AB  - Very few studies have examined quality of life (QOL) in elderly carers of
      orphaned children in African settings. This study explored sociodemographic
      factors and health-related characteristics that influence QOL of grandparent
      carers in Zimbabwe. A cross-sectional study stratified by district was done to
      collect information on socioeconomic factors, health-related characteristics, and
      QOL of grandparent carers (N = 327; age: M = 62.4, SD = 11.2). Data were
      collected on socioeconomic factors, self-perceived health, health care access,
      chronic disease condition, health insurance status, types of health care
      services, and medications taken using the World Health Organization Quality of
      Life Questionnaire (WHOQOL-BREF). Bivariate and multivariate analyses were used
      to investigate the associations between QOL and the predictor variables.
      Caregivers' level of education (odds ratio [OR] = 3.0; confidence interval [95%
      CI] = [1.0, 27]), fostering orphans only (OR = 0.4; 95% CI = [0.2, 0.7]), self
      perceived health (OR = 10.2; 95% CI = [4.5, 25]), medical insurance (OR = 9.8;
      95% CI = [1.9, 54]), and satisfaction with health care services (OR = 2.2; 95% CI
      = [1.2, 4.4]) were associated with QOL, after adjusting for all influencing
      factors. The results confirm that QOL is compromised by specific demographic and
      self-rated health characteristics. Thus, eradicating poverty and providing
      services and changing caregiver's perceptions about self-rated health may enhance
      QOL among grandparent caregivers.

PMID- 29468188
TI  - The association between non-standard employment, job insecurity and health among
      British adults with and without intellectual impairments: Cohort study.
AB  - We sought to investigate the association between employment conditions and health
      among working age British adults with and without intellectual impairments. Using
      data from the 1970 British Cohort Study, we undertook a series of cross sectional
      analyses of the association between employment conditions and health (self
      reported general health, mental health) among British adults with and without
      intellectual impairments at ages 30, 34 and 42. Our results indicated that: (1)
      British adults with intellectual impairments were more likely than their peers to
      be exposed to non-standard employment conditions and experience job insecurity;
      (2) in both groups exposure was typically associated with poorer health; (3)
      British adults with intellectual impairments in non-standard employment
      conditions were more likely than their peers to transition to economic
      inactivity; (4) among both groups, transitioning into employment was associated
      with positive health status and transitioning out of employment was associated
      with poorer health status. British adults with intellectual impairments are
      significantly more likely than their peers to be exposed to non-standard and more
      precarious working conditions. The association between employment conditions and
      health was similar for British adults with and without intellectual impairments.
      As such, the study found no evidence to suggest that research on causal pathways
      between employment and health derived from studies of the general population
      should not generalize to the population of people with intellectual impairments.

PMID- 29468189
TI  - Cytosolic ATP Relieves Voltage-Dependent Inactivation of T-Type Calcium Channels
      and Facilitates Excitability of Neurons in the Rat Central Medial Thalamus.
AB  - The central medial nucleus (CeM) is a part of the intralaminar thalamus, which is
      involved in the control of arousal and sensory processing. However, ionic
      conductances and mechanisms that regulate the activity of the CeM are not well
      studied. Here, we used in vitro electrophysiology in acute brain slices from
      adolescent rats to demonstrate that T-type calcium currents (T-currents) are
      prominent in the majority of the studied CeM neurons and are critical
      determinants of low-threshold calcium spikes (LTSs), which in turn regulate
      excitability of these neurons. Using an ATP-free internal solution decreased T
      current density and induced a profound hyperpolarizing shift in steady-state
      inactivation curves while voltage-dependent activation kinetics were spared.
      Furthermore, selective pharmacological blockade of T-channels or use of an ATP
      free solution reduced both tonic action potential (AP) frequency and rebound
      burst firing in CeM neurons. Our results indicate that T-channels are critical
      regulators of a thalamocortical circuit output and suggest that cytosolic ATP
      could be an endogenous regulatory mechanism in which T-channels may functionally
      gate sensory transmission and arousal in vivo.

PMID- 29468190
TI  - Optogenetic Activation of Non-Nociceptive Abeta Fibers Induces Neuropathic Pain
      Like Sensory and Emotional Behaviors after Nerve Injury in Rats.
AB  - Neuropathic pain is caused by peripheral nerve injury (PNI). One hallmark symptom
      is allodynia (pain caused by normally innocuous stimuli), but its mechanistic
      underpinning remains elusive. Notably, whether selective stimulation of non
      nociceptive primary afferent Abeta fibers indeed evokes neuropathic pain-like
      sensory and emotional behaviors after PNI is unknown, because of the lack of
      tools to manipulate Abeta fiber function in awake, freely moving animals. In this
      study, we used a transgenic rat line that enables stimulation of non-nociceptive
      Abeta fibers by a light-activated channel (channelrhodopsin-2; ChR2). We found
      that illuminating light to the plantar skin of these rats with PNI elicited pain
      like withdrawal behaviors that were resistant to morphine. Light illumination to
      the skin of PNI rats increased the number of spinal dorsal horn (SDH) Lamina I
      neurons positive to activity markers (c-Fos and phosphorylated extracellular
      signal-regulated protein kinase; pERK). Whole-cell recording revealed that
      optogenetic Abeta fiber stimulation after PNI caused excitation of Lamina I
      neurons, which were normally silent by this stimulation. Moreover, illuminating
      the hindpaw of PNI rats resulted in activation of central amygdaloid neurons and
      produced an aversion to illumination. Thus, these findings provide the first
      evidence that optogenetic activation of primary afferent Abeta fibers in PNI rats
      produces excitation of Lamina I neurons and neuropathic pain-like behaviors that
      were resistant to morphine treatment. This approach may provide a new path for
      investigating circuits and behaviors of Abeta fiber-mediated neuropathic
      allodynia with sensory and emotional aspects after PNI and for discovering novel
      drugs to treat neuropathic pain.

PMID- 29468191
TI  - A Neural Circuit Mechanism for the Involvements of Dopamine in Effort-Related
      Choices: Decay of Learned Values, Secondary Effects of Depletion, and Calculation
      of Temporal Difference Error.
AB  - Dopamine has been suggested to be crucially involved in effort-related choices.
      Key findings are that dopamine depletion (i) changed preference for a high-cost,
      large-reward option to a low-cost, small-reward option, (ii) but not when the
      large-reward option was also low-cost or the small-reward option gave no reward,
      (iii) while increasing the latency in all the cases but only transiently, and
      (iv) that antagonism of either dopamine D1 or D2 receptors also specifically
      impaired selection of the high-cost, large-reward option. The underlying neural
      circuit mechanisms remain unclear. Here we show that findings i-iii can be
      explained by the dopaminergic representation of temporal-difference reward
      prediction error (TD-RPE), whose mechanisms have now become clarified, if (1) the
      synaptic strengths storing the values of actions mildly decay in time and (2) the
      obtained-reward-representing excitatory input to dopamine neurons increases after
      dopamine depletion. The former is potentially caused by background neural
      activity-induced weak synaptic plasticity, and the latter is assumed to occur
      through post-depletion increase of neural activity in the pedunculopontine
      nucleus, where neurons representing obtained reward exist and presumably send
      excitatory projections to dopamine neurons. We further show that finding iv,
      which is nontrivial given the suggested distinct functions of the D1 and D2
      corticostriatal pathways, can also be explained if we additionally assume a
      proposed mechanism of TD-RPE calculation, in which the D1 and D2 pathways encode
      the values of actions with a temporal difference. These results suggest a
      possible circuit mechanism for the involvements of dopamine in effort-related
      choices and, simultaneously, provide implications for the mechanisms of TD-RPE
      calculation.

PMID- 29468192
TI  - Short-Term Depression of Axonal Spikes at the Mouse Hippocampal Mossy Fibers and
      Sodium Channel-Dependent Modulation.
AB  - Axonal spike is an important upstream process of transmitter release, which
      directly impacts on release probability from the presynaptic terminals. Despite
      the functional significance, possible activity-dependent modulation of axonal
      spikes has not been studied extensively, partly due to inaccessibility of the
      small structures of axons for electrophysiological recordings. In this study, we
      tested the possibility of use-dependent changes in axonal spikes at the
      hippocampal mossy fibers, where direct recordings from the axon terminals are
      readily feasible. Hippocampal slices were made from mice of either sex, and loose
      patch clamp recordings were obtained from the visually identified giant mossy
      fiber boutons located in the stratum lucidum of the CA3 region. Stimulation of
      the granule cell layer of the dentate gyrus elicited axonal spikes at the single
      bouton which occurred in all or none fashion. Unexpected from the digital nature
      of spike signaling, the peak amplitude of the second spikes in response to paired
      stimuli at a 50-ms interval was slightly but reproducibly smaller than the first
      spikes. Repetitive stimuli at 20 or 100 Hz also caused progressive use-dependent
      depression during the train. Notably, veratridine, an inhibitor of inactivation
      of sodium channels, significantly accelerated the depression with minimal effect
      on the initial spikes. These results suggest that sodium channels contribute to
      use-dependent depression of axonal spikes at the hippocampal mossy fibers,
      possibly by shaping the afterdepolarization (ADP) following axonal spikes.
      Prolonged depolarization during ADP may inactivate a fraction of sodium channels
      and thereby suppresses the subsequent spikes at the hippocampal mossy fibers.

PMID- 29468193
TI  - SCCmecFinder, a Web-Based Tool for Typing of Staphylococcal Cassette Chromosome
      mec in Staphylococcus aureus Using Whole-Genome Sequence Data.
AB  - Typing of methicillin-resistant Staphylococcus aureus (MRSA) is important in
      infection control and surveillance. The current nomenclature of MRSA includes the
      genetic background of the S. aureus strain determined by multilocus sequence
      typing (MLST) or equivalent methods like spa typing and typing of the mobile
      genetic element staphylococcal cassette chromosome mec (SCCmec), which carries
      the mecA or mecC gene. Whereas MLST and spa typing are relatively simple, typing
      of SCCmec is less trivial because of its heterogeneity. Whole-genome sequencing
      (WGS) provides the essential data for typing of the genetic background and
      SCCmec, but so far, no bioinformatic tools for SCCmec typing have been available.
      Here, we report the development and evaluation of SCCmecFinder for
      characterization of the SCCmec element from S. aureus WGS data. SCCmecFinder is
      able to identify all SCCmec element types, designated I to XIII, with subtyping
      of SCCmec types IV (2B) and V (5C2). SCCmec elements are characterized by two
      different gene prediction approaches to achieve correct annotation, a Basic Local
      Alignment Search Tool (BLAST)-based approach and a k-mer-based approach.
      Evaluation of SCCmecFinder by using a diverse collection of clinical isolates (n
      = 93) showed a high typeability level of 96.7%, which increased to 98.9% upon
      modification of the default settings. In conclusion, SCCmecFinder can be an
      alternative to more laborious SCCmec typing methods and is freely available at
      https://cge.cbs.dtu.dk/services/SCCmecFinder. IMPORTANCE SCCmec in MRSA is
      acknowledged to be of importance not only because it contains the mecA or mecC
      gene but also for staphylococcal adaptation to different environments, e.g., in
      hospitals, the community, and livestock. Typing of SCCmec by PCR techniques has,
      because of its heterogeneity, been challenging, and whole-genome sequencing has
      only partially solved this since no good bioinformatic tools have been available.
      In this article, we describe the development of a new bioinformatic tool,
      SCCmecFinder, that includes most of the needs for infection control professionals
      and researchers regarding the interpretation of SCCmec elements. The software
      detects all of the SCCmec elements accepted by the International Working Group on
      the Classification of Staphylococcal Cassette Chromosome Elements, and users will
      be prompted if diverging and potential new elements are uploaded. Furthermore,
      SCCmecFinder will be curated and updated as new elements are found and it is easy
      to use and freely accessible.

PMID- 29468194
TI  - Treatment of HIV-Infected Individuals with the Histone Deacetylase Inhibitor
      Panobinostat Results in Increased Numbers of Regulatory T Cells and Limits Ex
      Vivo Lipopolysaccharide-Induced Inflammatory Responses.
AB  - Histone deacetylase inhibitors (HDACi) modulate the transcriptional activity of
      all cells, including innate and adaptive immune cells. Therefore, we aimed to
      evaluate immunological effects of treatment with the HDACi panobinostat in HIV
      infected patients during a clinical phase IIa latency reversal trial. Using flow
      cytometry, we investigated changes in T cell activation (CD69, CD38, HLA-DR) and
      the expression of CD39 and CTLA4 on regulatory T cells (Tregs). Whole-blood
      stimulations were performed and cytokine responses measured using Luminex. Gene
      expression in purified peripheral blood mononuclear cells (PBMCs) was evaluated
      using an Affymetrix HTA 2.0 gene chip. We found that proportions of CD4+ and CD8+
      T cells expressing CD69 increased 24 h after initial panobinostat administration
      (P < 0.01), followed by an increase in the proportions of CD38+ HLA-DR+
      coexpressing CD4+ T cells on day 4 (P = 0.02). Concurrently, proportions of Tregs
      increased by 40% (P = 0.003). Treg CTLA4 median fluorescent intensity (MFI)
      increased by 25% (P = 0.007), and CD39 MFI on CD39+ Treg increased by 12% (P =
      0.02). Lipopolysaccharide (LPS)-induced inflammatory responses (interleukin-1beta
      [IL-1beta], IL-6, IL-12p40, and tumor necrosis factor alpha [TNF-alpha]) in whole
      blood were significantly downregulated 4 days after initial dosing. Lastly,
      panobinostat induced significant changes in the overall gene expression pattern
      (fold change, >1.5; false-discovery-rate [FDR]-corrected P, <0.05). Importantly,
      measures of immune function returned to baseline after panobinostat treatment and
      follow-up revealed no sustained effect on overall gene expression. IMPORTANCE The
      effect of treatment with histone deacetylase inhibitors on the immune system in
      HIV-infected individuals is not clear. Analysis of results from a clinical trial
      in which 15 HIV-infected individuals received 12 doses of panobinostat identified
      a significant impact on both T cell activation status and regulatory T cell
      suppressive marker expression and a reduced level of monocytic responsiveness to
      inflammatory stimuli. These changes were substantiated by global gene expression
      analysis. Collectively, the results suggest that panobinostat has multiple
      effects on innate and adaptive immune responses. Importantly, all the effects
      were transient, and further panobinostat treatment did not cause persistent long
      term changes in gene expression patterns in HIV-infected individuals.

PMID- 29468195
TI  - Transcriptome Profiling Reveals Interplay of Multifaceted Stress Response in
      Escherichia coli on Exposure to Glutathione and Ciprofloxacin.
AB  - We have previously reported that supplementation of exogenous glutathione (GSH)
      promotes ciprofloxacin resistance in Escherichia coli by neutralizing antibiotic
      induced oxidative stress and by enhancing the efflux of antibiotic. In the
      present study, we used a whole-genome microarray as a tool to analyze the system
      level transcriptomic changes of E. coli on exposure to GSH and/or ciprofloxacin.
      The microarray data revealed that GSH supplementation affects redox function,
      transport, acid shock, and virulence genes of E. coli. The data further
      highlighted the interplay of multiple underlying stress response pathways
      (including those associated with the genes mentioned above and DNA damage repair
      genes) at the core of GSH, offsetting the effect of ciprofloxacin in E. coli. The
      results of a large-scale validation of the transcriptomic data using reverse
      transcription-quantitative PCR (RT-qPCR) analysis for 40 different genes were
      mostly in agreement with the microarray results. The altered growth profiles of
      12 different E. coli strains carrying deletions in the specific genes mentioned
      above with GSH and/or ciprofloxacin supplementation implicate these genes in the
      GSH-mediated phenotype not only at the molecular level but also at the functional
      level. We further associated GSH supplementation with increased acid shock
      survival of E. coli on the basis of our transcriptomic data. Taking the data
      together, it can be concluded that GSH supplementation influences the expression
      of genes of multiple stress response pathways apart from its effect(s) at the
      physiological level to counter the action of ciprofloxacin in E. coli. IMPORTANCE
      The emergence and spread of multidrug-resistant bacterial strains have serious
      medical and clinical consequences. In addition, the rate of discovery of new
      therapeutic antibiotics has been inadequate in last few decades. Fluoroquinolone
      antibiotics such as ciprofloxacin represent a precious therapeutic resource in
      the fight against bacterial pathogens. However, these antibiotics have been
      gradually losing their appeal due to the emergence and buildup of resistance to
      them. In this report, we shed light on the genome-level expression changes in
      bacteria with respect to glutathione (GSH) exposure which act as a trigger for
      fluoroquinolone antibiotic resistance. The knowledge about different bacterial
      stress response pathways under conditions of exposure to the conditions described
      above and potential points of cross talk between them could help us in
      understanding and formulating the conditions under which buildup and spread of
      antibiotic resistance could be minimized. Our findings are also relevant because
      GSH-induced genome-level expression changes have not been reported previously for
      E. coli.

PMID- 29468198
TI  - Paraganglioma of Urinary Bladder Managed by Laparoscopic Partial Cystectomy in
      Conjunction with Flexible Cystoscopy: A Case Report.
AB  - Background: Paraganglioma of the urinary bladder (PUB) is exceedingly rare,
      accounting for <0.1% of all urinary bladder tumors. Various challenging treatment
      options are available. Case Presentation: A 67-year-old female presented with
      malignant hypertension on four medications for which investigation was done. An
      observation of having functioning PUB was noted. She was admitted and
      laparoscopic partial cystectomy was done with the guidance of flexible
      cystoscopy. She had a smooth postoperative course and was discharged home, then
      catheter was removed after cystogram. Histopathology confirmed the diagnosis of a
      bladder paraganglioma. Finally, during the last follow-up, the patient was
      asymptomatic with controlled blood pressure and normalized catecholamine levels
      with no evidence of recurrence. Conclusion: PUB is an exceedingly rare tumor that
      can be managed with minimally invasive techniques such as laparoscopic partial
      cystectomy with cystoscopy guidance.

PMID- 29468196
TI  - Altered Distribution of RNA Polymerase Lacking the Omega Subunit within the
      Prophages along the Escherichia coli K-12 Genome.
AB  - The RNA polymerase (RNAP) of Escherichia coli K-12 is a complex enzyme consisting
      of the core enzyme with the subunit structure alpha2betabeta'omega and one of the
      sigma subunits with promoter recognition properties. The smallest subunit, omega
      (the rpoZ gene product), participates in subunit assembly by supporting the
      folding of the largest subunit, beta', but its functional role remains unsolved
      except for its involvement in ppGpp binding and stringent response. As an initial
      approach for elucidation of its functional role, we performed in this study ChIP
      chip (chromatin immunoprecipitation with microarray technology) analysis of wild
      type and rpoZ-defective mutant strains. The altered distribution of RpoZ
      defective RNAP was identified mostly within open reading frames, in particular,
      of the genes inside prophages. For the genes that exhibited increased or
      decreased distribution of RpoZ-defective RNAP, the level of transcripts increased
      or decreased, respectively, as detected by reverse transcription-quantitative PCR
      (qRT-PCR). In parallel, we analyzed, using genomic SELEX (systemic evolution of
      ligands by exponential enrichment), the distribution of constitutive promoters
      that are recognized by RNAP RpoD holoenzyme alone and of general silencer H-NS
      within prophages. Since all 10 prophages in E. coli K-12 carry only a small
      number of promoters, the altered occupancy of RpoZ-defective RNAP and of
      transcripts might represent transcription initiated from as-yet-unidentified host
      promoters. The genes that exhibited transcription enhanced by RpoZ-defective RNAP
      are located in the regions of low-level H-NS binding. By using phenotype
      microarray (PM) assay, alterations of some phenotypes were detected for the rpoZ
      deleted mutant, indicating the involvement of RpoZ in regulation of some genes.
      Possible mechanisms of altered distribution of RNAP inside prophages are
      discussed. IMPORTANCE The 91-amino-acid-residue small-subunit omega (the rpoZ
      gene product) of Escherichia coli RNA polymerase plays a structural role in the
      formation of RNA polymerase (RNAP) as a chaperone in folding the largest subunit
      (beta', of 1,407 residues in length), but except for binding of the stringent
      signal ppGpp, little is known of its role in the control of RNAP function. After
      analysis of genomewide distribution of wild-type and RpoZ-defective RNAP by the
      ChIP-chip method, we found alteration of the RpoZ-defective RNAP inside open
      reading frames, in particular, of the genes within prophages. For a set of the
      genes that exhibited altered occupancy of the RpoZ-defective RNAP, transcription
      was found to be altered as observed by qRT-PCR assay. All the observations here
      described indicate the involvement of RpoZ in recognition of some of the prophage
      genes. This study advances understanding of not only the regulatory role of omega
      subunit in the functions of RNAP but also the regulatory interplay between
      prophages and the host E. coli for adjustment of cellular physiology to a variety
      of environments in nature.

PMID- 29468199
TI  - A Large Stone Within a Ureteroceles: A Diagnostic Pitfall and the Utility of
      Holmium Laser Deroofing as a Viable Surgical Option.
AB  - We describe a case of a partial unilateral duplex system and ureterocele
      containing a 4 cm stone in a 66-year-old woman who presented with renal colic.
      Cystoscopic stone removal and deroofing of the ureterocele were performed and a
      ureteral stent was placed for a total of 6 weeks. Our case is unique as it
      highlighted the diagnostic pitfalls of ureteroceles, especially when obscured by
      a large calculus. We also described the use of a Holmium laser to simultaneously
      incise the ureterocele and fragment the calculus.

PMID- 29468197
TI  - Genomewide Transcriptional Responses of Iron-Starved Chlamydia trachomatis Reveal
      Prioritization of Metabolic Precursor Synthesis over Protein Translation.
AB  - Iron is essential for growth and development of Chlamydia. Its long-term
      starvation in cultured mammalian cells leads to production of aberrant
      noninfectious chlamydial forms, also known as persistence. Immediate
      transcriptional responses to iron limitation have not been characterized, leaving
      a knowledge gap of how Chlamydia regulates its response to changes in iron
      availability. We used the fast-chelating agent 2,2'-bipyridyl (BPDL) to
      homogeneously starve Chlamydia trachomatis serovar L2 of iron, starting at 6 or
      12 h postinfection. Immediate transcriptional responses were monitored after only
      3 or 6 h of BPDL treatment, well before formation of aberrant Chlamydia. The
      first genomewide transcriptional response of C. trachomatis to iron starvation
      was subsequently determined utilizing RNA sequencing. Only 7% and 8% of the
      genome were differentially expressed in response to iron starvation at the early
      and middle stages of development, respectively. Biological pathway analysis
      revealed an overarching theme. Synthesis of macromolecular precursors
      (deoxynucleotides, amino acids, charged tRNAs, and acetyl coenzyme A [acetyl
      CoA]) was upregulated, while energy-expensive processes (ABC transport and
      translation) were downregulated. A large fraction of differentially downregulated
      genes are involved in translation, including those encoding ribosome assembly and
      initiation and termination factors, which could be analogous to the translation
      downregulation triggered by stress in other prokaryotes during stringent
      responses. Additionally, transcriptional upregulation of DNA repair, oxidative
      stress, and tryptophan salvage genes reveals a possible coordination of responses
      to multiple antimicrobial and immunological insults. These responses of
      replicative-phase Chlamydia to iron starvation indicate a prioritization of
      survival over replication, enabling the pathogen to "stock the pantry" with
      ingredients needed for rapid growth once optimal iron levels are restored.
      IMPORTANCE By utilizing an experimental approach that monitors the immediate
      global response of Chlamydia trachomatis to iron starvation, clues to long
      standing issues in Chlamydia biology are revealed, including how Chlamydia adapts
      to this stress. We determined that this pathogen initiates a transcriptional
      program that prioritizes replenishment of nutrient stores over replication,
      possibly in preparation for rapid growth once optimal iron levels are restored.
      Transcription of genes for biosynthesis of metabolic precursors was generally
      upregulated, while those involved in multiple steps of translation were
      downregulated. We also observed an increase in transcription of genes involved in
      DNA repair and neutralizing oxidative stress, indicating that Chlamydia employs
      an "all-or-nothing" strategy. Its small genome limits its ability to tailor a
      specific response to a particular stress. Therefore, the "all-or-nothing"
      strategy may be the most efficient way of surviving within the host, where the
      pathogen likely encounters multiple simultaneous immunological and nutritional
      insults.

PMID- 29468200
TI  - Robot-Assisted Perineal Radical Prostatectomy in a Post-Kidney Transplant
      Recipient.
AB  - Background: After almost two decades, transabdominal robotic radical
      prostatectomy techniques have been fully developed and are widely practiced by
      many robotic urologists. Recently, a transperineal robotic radical prostatectomy,
      a technique not yet popular to many, was introduced as an alternative approach in
      patients with previous abdominal surgery. Here, we present our unique experience
      with robotic perineal radical prostatectomy (r-PRP) on a kidney transplant
      recipient. Case Presentation: A 71-year-old man who had a kidney transplant 4
      months previously was diagnosed with prostate cancer (PCa) and underwent r-PRP
      using the da Vinci Xi robotic system. The operative time was 110 minutes and
      blood loss was minimal. After the perineal drain was removed on postoperative day
      3, the patient was discharged. The urethral catheter was subsequently removed on
      postoperative day 8. Pathologic analysis revealed localized PCa with negative
      surgical margins. Conclusion: The r-PRP offers all the advantages of minimally
      invasive surgery. Moreover, in a kidney transplant recipient, it provides
      additional benefits, such as avoidance of allograft vascular and ureteral
      injuries, while maintaining an equivalent oncologic efficacy and surgical safety
      compared with its transabdominal counterpart.

PMID- 29468201
TI  - Toward a More Humanistic American Medical Profession: An Analysis of Premedical
      Web Sites From Ohio's Undergraduate Institutions.
AB  - In response to changes in health care, American medical schools are transforming
      their curricula to cultivate empathy, promote professionalism, and increase
      cultural competency. Many scholars argue that an infusion of the humanities in
      premedical and medical training may help achieve these ends. This study analyzes
      Web-based messaging of Ohio's undergraduate institutions to assess premedical
      advising attitudes toward humanities-based coursework and majors. Results suggest
      that although many institutions acknowledge the humanities, most steer students
      toward science majors; strong advocates of the humanities tend to have religious
      or other special commitments, and instead of acknowledging the intrinsic value
      that the humanities might have for future physicians, most institutions promote
      the humanities because entrance exams now contain related material.

PMID- 29468202
TI  - Pramipexole-induced antecollis in patients with Parkinson's disease: Two cases
      and literature review.
AB  - Antecollis is considered to be relatively rare in Parkinson's disease (PD). Few
      cases of dopamine agonist-induce antecollis in PD have been reported. We
      described literature review of 12 PD patients including our 2 cases with
      pramipexole (PPX)-induced antecollis. The patients were predominantly Japanese,
      women and above 3 of Hoehn and Yahr stage. PPX-induced antecollis in PD was
      considered a type of dystonia of flexor neck muscle, and was improved soon after
      cessation or reduction of PPX. Our two cases improved their antecollis by
      overnight changing from PPX to ropinirole without deteriorating motor functions.
      Overnight switching of DA was considered useful as one option in the treatment of
      antecollis.

PMID- 29468203
TI  - Inner retinal vasculopathy in Zika virus disease.
AB  - Purpose: Zika virus infection is associated with vision-threatening ocular
      complications including uveitis and outer retinopathy. The aim of this report is
      to describe a case of an adult patient with serologically confirmed Zika
      infection who presented with retinal vascular abnormalities that coincided with
      systemic post-viral neurological manifestations of the disease. Observations: A
      34-year-old white female presented with symptoms of peripheral neuropathy
      following serologically confirmed Zika virus infection that was acquired in
      Puerto Rico four months prior to presentation. Ocular evaluation revealed
      perifoveal microaneurysms which were not associated with visual symptoms.
      Conclusions and importance: These data potentially expand the phenotypic spectrum
      of Zika virus retinopathy. In addition to outer retinal abnormalities which are
      well-described in infants and adults, inner retinal vascular abnormalities may
      also occur and may be temporally associated with post-viral neurological sequelae
      of Zika virus infection. Clinicians should be aware of potential retinal
      involvement in affected patients who present with neurological symptoms after
      recovery from acute Zika virus infection.

PMID- 29468204
TI  - Orbital apex syndrome from bacterial sinusitis without orbital cellulitis.
AB  - Purpose: To describe a case of orbital apex syndrome as a result of isolated
      bacterial sinusitis. Observations: A 63-year-old woman presented with an orbital
      apex syndrome from isolated bacterial sinusitis with rapidly declining visual
      acuity to no light perception. We compared our case with 6 similar cases of
      severe vision loss from isolated bacterial sinusitis. In contrast to previously
      published cases, our patient presented with good vision yet deteriorated to no
      light perception despite appropriate treatment. Conclusions and importance:
      Orbital apex syndrome can present as a constellation of cranial neuropathies
      including optic neuropathy from conditions affecting the orbital apex. Although
      vision loss remained permanent, prompt initiation of broad-spectrum antibiotics
      and antifungals and surgical intervention prevented further extension of
      infection into intracranial structures.

PMID- 29468205
TI  - Late-onset bleb-associated endophthalmitis and continuous positive airway
      pressure.
AB  - Purpose: To raise awareness of a possible association between continuous positive
      airway pressure (CPAP) devices and postoperative bleb-related infection.
      Observations: A 57-year old patient on CPAP presented with unilateral bleb
      associated endophthalmitis 32 months after routine ExPress Trabeculectomy with
      mitomycin C. The offending organism, Streptococcus mitis, is a nonmotile and
      generally non-virulent pathogen which predominates in the normal human
      respiratory flora. Conclusions and importance: This conceptual report underscores
      a potential relationship between CPAP use and bleb-associated endophthalmitis.
      Streptococcal species are the most commonly reported causative organisms in bleb
      associated endophthalmitis, and S. mitis is of particular concern as the most
      abundant microbe among all human oral flora. A logical risk factor for infection,
      the CPAP device may inadvertently deliver such organisms to the vulnerable
      conjunctival filtering bleb.

PMID- 29468206
TI  - Severe visual loss and recovery post trabeculectomy- A case report.
AB  - Purpose: Glaucoma is a progressive optic neuropathy and a leading cause of
      blindness. Neural losses from glaucoma are irreversible, and so the aim of
      glaucoma treatment is to slow progression and minimize the risk of further
      damage. Visual loss post filtration surgery in patients with advanced
      glaucomatous optic nerve damage is a rare but dreaded complication. Functional
      improvement is not expected. We report the case of a patient who experienced a
      significant loss of vision following glaucoma surgery that was followed by late
      visual recovery. We will also review the literature regarding this phenomenon.
      Case presentation/Observations: A 60-year old male presented with a history of
      right pseudoexfoliative glaucoma and uncontrolled intraocular pressure(IOP) on
      medical and laser treatment. He underwent a successful right Mitomycin C
      augmented trabeculectomy combined with phacoemulsification. Unexpectedly, he
      experienced a marked decrease in vision from 0.3 to hand motion with no
      identifiable explanation. The loss of vision continued for almost 4 months before
      a significant improvement in vision occurred and his visual acuity came up to
      0.6. Although the mechanism of loss or improved vision cannot be proven, it is
      likely that post operative IOP spikes which were repeatedly above 30 mmHg in the
      first week, resulted in ganglion cell dysfunction rather than apoptosis which can
      explain the improvement in vision in the later months when pressure was
      maintained at target. Conclusion: and Importance: Although rare, Wipe out
      phenomenon is possible in the setting of advanced glaucomatous optic neuropathy.
      However, functional improvements may occur following IOP control. Glaucoma
      surgery should be offered early to those with advanced disease.

PMID- 29468207
TI  - Bull's eye maculopathy and subfoveal deposition in two mucopolysaccharidosis type
      I patients on long-term enzyme replacement therapy.
AB  - Purpose: To report retinal findings in two patients with mucopolysaccharidosis
      type I (MPS I) receiving human recombinant alpha-l-iduronidase (Laronidase) as
      enzyme replacement therapy. Observations: Patient 1 had visual acuity 20/20 right
      eye, 20/25 left eye and unremarkable anterior segment and retinal examination.
      Optical coherence tomography (OCT) scanning demonstrated parafoveal thinning and
      subfoveal hyperreflectant material. Patient 2 had visual acuity 20/20 both eyes,
      with dense nuclear cataract both eyes. Retinal examination demonstrated bull's
      eye maculopathy both eyes. OCT scanning confirmed parafoveal atrophy and
      demonstrated similar appearing subfoveal hyperreflectant material, more prominent
      than in case 1. Conclusions and importance: These two patients with MPS I
      receiving Laronidase treatment have developed bull's eye maculopathy changes and
      subfoveal deposition of hyperreflectant material despite excellent compliance and
      good tolerance of the standard dose of enzyme therapy for this disorder. Further
      studies are required to determine the nature of the material, the incidence and
      the effect of enzyme replacement therapy on these findings in patients with MPS
      I.

PMID- 29468208
TI  - Novel use of fibrin sealant for scleral suture free placement of a glaucoma
      drainage device in advanced scleral thinning.
AB  - Purpose: This reports a case using fibrin glue to secure a glaucoma drainage
      device plate to the sclera where there is a concern with the use of suture.
      Observations: A 13-year-old patient with congenital aniridia and associated
      glaucoma refractory to topical medications underwent implantation of a glaucoma
      drainage device (GDD) for improved intraocular pressure (IOP) control. The
      patient had substantial scleral thinning with staphyloma formation, potentially
      making the use of traditional suturing techniques problematic. Fibrin glue was
      used to attach the GDD plate, as well the tube and patch graft which has been
      previously described, without sutures. The patient tolerated the procedure well
      with a 41% reduction in IOP at six months follow-up with no migration of the GDD
      from its original position. Conclusions and importance: The use of fibrin glue in
      ophthalmology can be expanded to include attachment of the GDD plate to the
      sclera in patients with suturing contraindications.

PMID- 29468209
TI  - Juvenile xanthogranuloma involving concurrent iris and skin: Clinical,
      pathological and molecular pathological evaluations.
AB  - Purpose: To report a case of juvenile xanthogranuloma involving the iris and skin
      that clincally was diagnosed with an obvious cutaneous lesion. Observations: A
      four month-old girl with hyphema and increased intraocular pressure of the left
      eye persisting for 2 weeks. A suspicious yellow-brown mass with nodular surface
      and traversed by irregular vascularization was noted on the inferior iris
      surface. Ultrasound biomicroscopy (UBM; 35 MHz) of the mass revealed multiple
      nodular irregular hyperreflective lesions in the peripheral iris. Using a biopsy
      of an obvious cutaneous abdominal skin lesion a diagnosis was made based on
      histopathological analyses. The biopsy showed dense dermal infiltrate consisting
      of foamy histiocytes. Additional stains revealed CD68 positivity and CD1a and
      S100 negativity. This mass revealed histopathologic features identical to
      juvenile xanthogranuloma and was concurrent with the iris lesion. Next-generation
      sequencing using Ion AmpliSeqTM Cancer Hotspot Panel revealed a missense mutation
      of FGFR3 (p.F386L). Conclusion and importance: The diagnosis of a xanthogranuloma
      of the iris with hyphema can be made easier in patients with obvious cutaneous
      lesions as described in our case. The significance of FGFR3 mutation in
      association with JXG is unknown and should be further investigated.

PMID- 29468210
TI  - Removal of choroidal neovascular membrane in a case of macular hole after anti
      VEGF therapy for age-related macular degeneration.
AB  - Purpose: The formation of macular hole after receiving anti-vascular endothelial
      growth factor (anti-VEGF) therapy is rare. We report a case of macular hole that
      occurred after intravitreal injection of an anti-VEGF agent for age-related
      macular degeneration (AMD) in a patient, who underwent vitrectomy combined with
      choroidal neovascularization (CNV) removal. Observations: A 64-year-old female
      with AMD affecting her right eye received an intravitreal injection of an anti
      VEGF agent. After treatment, we identified a full thickness macular hole (MH)
      that was associated with the rapid resolution of the macular edema and
      contraction of the CNV. After performing vitrectomy combined with CNV removal,
      the MH closed and her visual acuity improved. Examination of the removed CNV
      revealed a network of microvessels devoid of pericytes. Conclusions: and
      Importance: The present findings suggest that rapid resolution of macular edema
      and contraction of the CNV and/or mild increase in the vitreous traction after
      anti-VEGF therapy could potentially cause MH. CNV removal via the MH may be an
      acceptable procedure, if the MH remains open, the CNV is of the classic type, and
      it spares a central portion of the fovea.

PMID- 29468211
TI  - Treatment of retinal pigment epithelial detachment secondary to exudative age
      related macular degeneration.
AB  - Purpose: This pilot study evaluated the combination of photodynamic therapy (PDT)
      and anti-vascular endothelial growth factor (anti-VEGF) as a treatment in
      patients with a pigment epithelial detachment (PED) due to exudative age-related
      degeneration (AMD). Methods: We analyzed seven consecutive patients between
      September 1, 2015 and September 1, 2017 with a PED secondary to exudative AMD who
      were treated with full fluence standard PDT and a series of monthly intravitreal
      anti-VEGF injections. Follow-up ranged between 3 and 24 months. Variables
      collected for the purpose of this study included baseline best-corrected visual
      acuity converted to logMAR (logarithm of minimum angle of resolution), central
      macular thickness, and maximum PED height. This information was then reviewed at
      subsequent follow-ups. Results: The PED completely resolved in 4/7 eyes while
      three patients had a significant improvement in PED size with a corresponding
      improvement in visual acuity. Initial PED heights ranged from 147 to 423 MUm and
      was reduced by an average of 255.7 MUm (83.2% average reduction, range -143 to -
      405 MUm). Initial CMT ranged from 223 to 719 MUm and was reduced by an average of
      225.7 MUm (54.4% average reduction, range -88 to - 529 MUm). Mean logMAR VA
      improved from 0.669 (Snellen equivalent 20/93, [20/40 to 20/200]) to 0.269
      (Snellen equivalent 20/37, [20/25 to 20/80]) at last follow-up. No complications
      were observed in our patients. Conclusions and Importance: PED in the setting of
      exudative AMD showed an excellent response to a combined multimodal approach that
      includes PDT with intravitreal anti-VEGF injection followed by a monthly anti
      VEGF schedule. Most importantly, visual acuity showed a significant improvement
      from baseline. If confirmed by future studies, this would offer another treatment
      avenue for this difficult-to-treat consequence of exudative AMD.

PMID- 29468212
TI  - Retinal pigment epithelium changes in pediatric patients with glaucoma drainage
      devices.
AB  - Purpose: Retinal changes secondary to hypotony are usually described as wrinkling
      or folding of the inner portion of the choroid, the retinal pigment epithelium
      (RPE), and the outer retinal layers in the macular area due to scleral wall
      collapse. We describe a new retinal finding in children with suspected hypotony
      after implantation of Baerveldt Glaucoma Implant (BGI). Observations: Four
      patients in our series developed significant RPE defects after BGI implant. The
      RPE defects appeared as elongated white lines observed solely in the posterior
      pole, in no particular pattern, and seemed to be worse in infants with anterior
      segment dysgenesis and with collagen disorders. Conclusion and importance:
      Children have thinner and more elastic scleral walls than adults. This
      characteristic may cause the inward scleral wall to collapse when the eye is
      hypotonic. The resulting redundancy of the retina leads to wrinkling and RPE
      defects characterized by hypopigmented lines predominantly in the macular area.
      Such findings, to our knowledge, have not been previously reported in pediatric
      patients.

PMID- 29468213
TI  - Acute-onset endophthalmitis caused by Staphylococcus lugdunensis.
AB  - Purpose: To report a series of patients with acute-onset bacterial
      endophthalmitis caused by culture proven Staphylococcus lugdunensis, and to
      characterize clinical outcomes and microbiologic susceptibilities of this
      organism. Observations: The study included six eyes of 6 patients. The etiologies
      included cataract surgery (3), open globe injury (2), and intravitreal injection
      (1). Isolates of S. lugdunensis demonstrated sensitivity to vancomycin in all
      cases reported. Three of 6 isolates of S. lugdunensis demonstrated resistance to
      oxacillin and 1 isolate demonstrated resistance to ciprofloxacin. Best-corrected
      visual acuity was >=20/400 in 6/6 (100%) of eyes and >=20/40 in 3/6 (50%) of
      cases. Conclusion and importance: Acute-onset endophthalmitis caused by S.
      lugdunensis is associated with variable visual outcomes. Vancomycin provides
      consistent coverage of acute-onset endophthalmitis cause by S. lugdunensis.

PMID- 29468214
TI  - Optical coherence tomography angiography showing perifoveal capillary stability
      30 years after fluorescein angiography.
AB  - Purpose: To report the Optical Coherence Tomography Angiography (OCTA) results as
      a novel non-invasive diagnostic modality which provides useful information
      regarding the status of blood flow in diabetic retinopathy. The current study is
      a long-term follow-up of eyes of patients with proliferative diabetic retinopathy
      managed with panretinal photocoagulation. Observations: Two patients with
      proliferative diabetic retinopathy (PDR) were treated with panretinal
      photocoagulation (PRP) in both eyes in the early 1980s. Fluorescein angiography
      performed at the baseline visit and follow-up Optical Coherence Tomography
      Angiography performed at 30 years after initial PRP treatment showed remarkable
      stability of the perifoveal capillary network. Visual acuity initially and at
      last follow-up remained 20/25 or better in these patients. Conclusions and
      importance: Fluorescein angiography and Optical Coherence Tomography Angiography
      demonstrated that the integrity of the perifoveal capillary network remained
      remarkably stable at 30 years. Similarly, the visual outcomes were stable inspite
      of advanced PDR at baseline.

PMID- 29468215
TI  - Descemet membrane endothelial keratoplasty for corneal decompensation due to
      iridoschisis.
AB  - Purpose: To report a case of bilateral iridoschisis with cataracts and corneal
      decompensation in a patient who underwent cataract extraction and superficial
      iridectomy followed by Descemet membrane endothelial keratoplasty (DMEK).
      Observations: A 58-year-old man with previously diagnosed iridoschisis,
      cataracts, and diabetes mellitus experienced progressive vision loss bilaterally
      due to corneal decompensation. Slit lamp examination revealed iridoschisis with
      iris fibrils contacting the corneal endothelium, stromal edema, and mild guttate
      changes bilaterally. Corneal findings were more severe in the right eye,
      including the presence of bullous keratopathy at the time of presentation.
      Cataract extraction with intraocular lens implantation and superficial iridectomy
      were performed in the right eye, followed by DMEK. These same procedures were
      performed subsequently in the left eye. Postoperatively, the patient had
      significant improvement in visual acuity and corneal edema. Conclusions and
      importance: DMEK can be performed safely and successfully after staged cataract
      surgery with superficial iridectomy in eyes with endothelial decompensation
      caused by iridoschisis.

PMID- 29468216
TI  - Central retinal artery occlusion during vitrectomy: Immediate retinal
      revascularization following induction of posterior vitreous detachment.
AB  - Purpose: To describe a patient with acute central retinal artery occlusion (CRAO)
      during vitrectomy surgery and the possible role of vitrectomy in acute CRAO
      management. Observations: An 84-year-old man presented with broad vitreomacular
      traction and epiretinal membrane in the right eye. Preoperative assessment
      clearly showed normal retinal vasculature. On starting vitrectomy, complete CRAO
      with marked segmentation of all retinal vessels was noted. Vitrectomy was
      performed in the usual manner and once the posterior hyaloid detached from the
      disc, immediate complete revascularization of the retinal vessels was noted. The
      patient had a complete visual recovery. Conclusions and importance: Immediate
      vitrectomy with induction of posterior vitreous detachment may have a role in
      selected cases of acute CRAO, particularly if performed within a short window.

PMID- 29468217
TI  - Ranibizumab-induced retinal reperfusion and regression of neovascularization in
      diabetic retinopathy: An angiographic illustration.
AB  - Purpose: To report regression of neovascularization and reperfusion of ischemic
      areas of the retina on Wide-field Digital Fluorescein Angiography following anti
      vascular endothelial growth factor injections in a patient with active
      Proliferative Diabetic Retinopathy. Observations: Case report of sixty-one-year
      old male patient with proliferative diabetic retinopathy and diabetic macular
      edema documented on wide field digital fluorescein angiography. The patient was
      treated with three intravitreal injections of ranibizumab given at monthly
      intervals. Repeat angiography after third intravitreal injection revealed
      complete regression of new vessels. Moreover, there was evident improvement in
      perfusion in the previously noted ischemic areas of the retina. Conclusion and
      importance: Intravitreal anti-vascular endothelial growth factor (anti-VEGF)
      injections are a valuable treatment option for reversing neovascularization in
      eyes with proliferative diabetic retinopathy with fewer side effects when
      compared to standard pan-retinal photocoagulation. Additionally, we also
      illustrate restoration of retinal perfusion post anti-VEGF therapy indicative of
      pre-existingsalvageableischemic retina tissue.

PMID- 29468218
TI  - Intravitreal bevacizumab as therapy for refractory neovascular glaucoma secondary
      to iris metastasis of breast carcinoma.
AB  - Purpose: To report a case of refractory glaucoma secondary to iris metastasis
      from breast cancer which was successfully treated with intravitreal bevacizumab.
      Observations: A 72-year-old woman presented with left ocular pain, vision loss
      and neovascular glaucoma secondary to iris metastasis from breast cancer. A
      single intravitreal injection of bevacizumab resulted in prolonged resolution of
      iris neovascularization, reduction of intraocular pressure and ocular pain
      relief. Iris tumor regression was later noted following the reinstatement of
      systemic chemotherapy. Conclusions & importance: A single intravitreal
      bevacizumab injection may be sufficient to achieve palliative control of
      neovascular glaucoma secondary to iris breast cancer metastasis. To our
      knowledge, this is the first case report in which a single intravitreal
      bevacizumab injection was used for the effective management of this condition.

PMID- 29468219
TI  - Retinal vasproliferative tumor in a case of X-linked retinoschisis detachment.
AB  - Purpose: To describe the first published case of X-linked retinoschisis (XLRS)
      detachment with retinal vasoproliferative tumor (RVPT) and provide a literature
      review of the subject. Observations: The authors describe a case of a 17 year old
      male with X-linked retinoschisis who presented with a retinal detachment and a
      retinal vasoproliferative tumor. The patient was treated with pars plana
      vitrectomy, endolaser, subtenon's kenalog and anti-VEGF (vascular endothelial
      growth factor) intravitreal injections. He regained 20/60 vision with a flat
      macula and had significant resolution of the associated vasoproliferative leakage
      seen on fluorescein angiography. Conclusions and importance: This case adds XLRS
      to the conditions associated with RVPT and gives support for treatment with laser
      photocoagulation and anti-VEGF therapy with bevacizumab to control the exudative
      process.

PMID- 29468220
TI  - Optical coherence tomography angiography changes in radial peripapillary
      capillaries in Leber hereditary optic neuropathy.
AB  - Purpose: To present a report of longitudinal changes in radial peripapillary
      capillaries (RPC) and changes in retinal full thickness (RFT) and peripapillary
      retinal nerve fiber layer (RNFL) in a patient with Leber hereditary optic
      neuropathy (LHON). Observations: A 42-year-old man presented with acute- and
      presymptomatic-stage LHON in the left (OS) and right (OD) eyes, respectively, at
      the initial visit. Onset of LHON in the OD was observed 2 months after the
      initial visit. Once the temporal RNFL started to decrease in thickness, the areas
      of temporal RPC defects and RFT thinning gradually increased, indicating that
      these factors might be correlated. Conclusions and importance: Optical coherence
      tomography angiography showed LHON from the presymptomatic stage. The results
      indicate that temporal RPC defects and RFT thinning start to spread once the
      pseudoedema begins to resolve.

PMID- 29468221
TI  - Spectral optical coherence tomography findings in an elderly patient with
      syphilitic bilateral chronic panuveitis.
AB  - Purpose: To report the spectral domain optical coherence tomography (SD-OCT)
      features of a focal retinitis in an elderly male patient with bilateral
      syphilitic panuveitis. Observations: In the left eye (LE), spectral domain SD-OCT
      images during the active period revealed hyperreflectivity extending through the
      full thickness of the retina with no individualization of the layers, except for
      the retinal pigment epithelium. Once the lesion healed, SD-OCT imaging revealed
      an inner retinal atrophy and a mild disruption of the retinal pigment epithelium.
      Conclusions and importance: In our patient, treponemal infection seemed to
      produce full-thickness retinal damage with partial involvement of the retinal
      pigment epithelium. The severe retinal damage, in this case, led to a poorer
      visual outcome than in other forms of syphilitic retinal involvement.

PMID- 29468222
TI  - Clinical features, antimicrobial susceptibilities, and treatment outcomes of
      patients with culture positive endophthalmitis after penetrating keratoplasty.
AB  - Purpose: To report the clinical features organisms and treatment outcomes in
      patients with endophthalmitis after penetrating keratoplasty (PK). Methods:
      Retrospective noncomparative case series. Results: Eleven eyes of 11 patients
      with culture positive endophthalmitis after PK were included. The time to
      diagnosis of endophthalmitis from last PK was less than 1 week in 3/11 (27%),
      between 1 and 4 weeks in 3/11 (27%), and greater than one month in 5/11 (46%)
      (range 2-924 days). The distribution of isolates included gram positive (GP) 9/11
      (82%), gram negative (GN) 1/11 (9%), and fungal 1/11 (9%) species, respectively.
      Of GP bacteria tested, 9/9 (100%) were sensitive to Vancomycin. Of fungal
      isolates tested, none (0/1) were sensitive to Amphoteracin, Fluconazole, and/or
      Voriconazole. Among patients with rim culture data available, 1/7 (14%) donor
      rims were culture positive for Candida glabrata and 6/7 (86%) were culture
      negative. Patients were treated with primary tap and inject in 10/11 (91%) and
      primary vitrectomy in 1/11 (9%). VA of >=5/200 was present in 2/11 (18%) at time
      of endophthalmitis diagnosis, and was recorded in 6/11 (55%) at last follow-up.
      Conclusions and Importance: Patients with endophthalmitis after PK presented at
      variable time points after surgery. Gram positive organisms were the most common
      isolate. VA outcomes after treatment were generally poor.

PMID- 29468223
TI  - A case of hypertrophic herpes simplex virus affecting the eyelid and cornea
      masquerading as IgG4-related disease.
AB  - Purpose: To report a case of hypertrophic herpes simplex virus (HSV) of the
      eyelid and cornea masquerading as IgG4-related disease. Observations: A 37-year
      old African American female with a past medical history of human immunodeficiency
      virus (HIV) on highly active antiretroviral therapy (HAART) and a recent history
      of treated genital herpes, presented with an ulcerative lesion of the left upper
      and lower eyelids, and severe ocular inflammation with symblepharon. Initially,
      eyelid biopsy revealed findings consistent with IgG4-related disease, and the
      patient was treated with high dose oral prednisone. After one week of therapy,
      there was no improvement in the patient's symptoms, and she subsequently
      developed a corneal epithelial defect which progressed to chronic ulceration.
      Repeat biopsy and corneal cultures revealed herpes simplex virus type 2. The
      patient was treated with high dose acyclovir, and the lid lesion improved. The
      conjunctival inflammation and corneal epithelial defect resolved but symblepharon
      restricting her eye movement remained. She also developed corneal vascularization
      and opacification causing severe vision loss. Conclusions and importance: Chronic
      hypertrophic herpes simplex virus infection is a rare condition reported in
      patients with HIV. While there have been few reports of hypertrophic HSV
      affecting the eyelid, this is the first reported case of hypertrophic HSV
      affecting the eye, resulting in severe vision loss.

PMID- 29468224
TI  - Optical coherence tomography angiography of a pigmented Fuchs' adenoma (age
      related hyperplasia of the nonpigmented ciliary body epithelium) masquerading as
      a ciliary body melanoma.
AB  - Purpose: To report a case of age-related hypertrophy of the nonpigmented ciliary
      epithelium (ARH-NPCE) clinically resembling a ciliary body melanoma and report
      the optical coherence tomography angiography (OCTA) findings associated with this
      lesion. Observations: A 51-year-old male was referred for evaluation of a deeply
      pigmented ciliary body mass with extension through the iris root. Iridocyclectomy
      was performed due to concern for ciliary body melanoma. Histopathologic analysis
      was instead consistent with ARH-NPCE, also known as Fuchs' adenoma. Prior to
      surgery, OCTA images revealed abnormal vasculature in the area of the lesion.
      Vessels in the peripheral iris approaching the lesion appeared more tortuous and
      were non-radial as compared with normal iris vessels. The ciliary body mass
      itself could not be penetrated using an OCTA system operating at 1050 nm.
      Conclusions and importance: ARH-NPCE may clinically resemble a pigmented ciliary
      body melanoma. This is the second case describing this clinical scenario, which
      may be more common than previously thought. Non-invasive imaging with OCTA
      revealed an abnormal peripheral iris vasculature pattern in the area of the
      iridociliary mass characterized by disorganized, tortuous, and non-radial
      vessels. Despite advances in longer wavelength OCTA systems, poor penetration of
      the ciliary body lesion precluded imaging of the intratumoral vessels in this
      location.

PMID- 29468225
TI  - Multimodal imaging of macular subretinal deposits following intravitreal
      ocriplasmin injection.
AB  - Purpose: Ocriplasmin is effective in closing macular holes due to vitreomacular
      traction. We present a case of macular subretinal material deposition observed
      with spectral-domain optical coherence tomography (SD-OCT) and multimodal
      imaging, following successful closure of a macular hole following intravitreal
      ocriplasmin injection. Observations: An 81-year-old male presented with decreased
      vision in the left eye due to a full-thickness macular hole secondary to
      vitreomacular traction. Ocriplasmin (Jetrea) was injected into the vitreous and
      hole closure was observed after one week. Macular subretinal material deposition
      developed along the outer surface of the resultant serous detachment on OCT one
      week post-injection. Fluorescein angiography demonstrated no expanding
      hyperfluorescence due to retinal or choroidal leak, or staining of the lesion.
      The material was mildly autofluorescent. The macular subretinal material complex
      spontaneously decreased with no significant effect on vision over 60 weeks.
      Conclusions and importance: Macular subretinal material deposition has not
      previously been reported following intravitreal ocriplasmin injection. This
      material is likely composed of photoreceptor outer segments. It is important to
      recognize that macular subretinal deposits can occur following intravitreal
      ocriplasmin injection as it may cause diagnostic confusion and potentially
      influence the visual and anatomical outcomes following successful hole closure.

PMID- 29468226
TI  - Immunoglobulin G4-related dacyroadenitis presenting as bilateral chorioretinal
      folds from severely enlarged lacrimal glands.
AB  - Purpose: To describe a case of immunoglobulin G4 (IgG4)-related dacyroadenitis
      presenting as bilateral chorioretinal folds from eyeball compression by massively
      enlarged lacrimal glands. Observations: A 51-year-old woman with severely
      enlarged bilateral lacrimal glands was diagnosed as having IgG4-related
      dacryoadenitis. The glands strongly compressed the globes, forming chorioretinal
      folds resembling those found in orbital malignancy. Eventual treatment with oral
      prednisolone dramatically reduced the volume of the lacrimal glands and released
      globe compression on magnetic resonance imaging. However, the chorioretinal folds
      remained in the right fundus and symptoms of blurred vision improved but
      persisted. Conclusions and importance: This is the first account of chorioretinal
      fold formation by severely enlarged lacrimal glands appearing in IgG4-related
      dacryoadenitis. Chorioretinal fold formation by an enlarged lacrimal gland
      occurring bilaterally may represent a basis for suspecting IgG4-related
      dacryoadenitis. Prompt treatment is recommended for patients presenting with very
      large lacrimal glands to avoid visual impairment.

PMID- 29468227
TI  - Solitary mastocytoma in the eyelid of an adult.
AB  - Purpose: To describe the ophthalmic symptoms and histopathological findings in a
      rare case of an eyelid mastocytoma in an adult. Observations: A man in his early
      60s developed a painless, non-tender, non-pruritic, mobile nodule on the right
      lower eyelid beneath the inferior orbital rim. The lesion grew to 15 * 9 mm over
      eleven months. Biopsy revealed a diffuse infiltrate of histiocytoid and spindle
      shaped mast cells forming cords and small nests between collagen fibers in the
      superficial and deep dermis. Mast cell lineage was confirmed by
      immunohistochemistry. Physical examination revealed no other cutaneous lesions
      and no evidence of systemic disease. Serum tryptase level was normal. Annual full
      body examination by a dermatologist for 4.5 years has revealed neither recurrence
      in the eyelid nor cutaneous involvement at other sites. Conclusions and
      importance: Mast cell tumors limited to the human eyelid are extremely uncommon
      with only four previously reported cases, including one in an adult. This case
      highlights the rare possibility of a solitary mastocytoma presenting in the
      eyelid of an adult.

PMID- 29468229
TI  - Penetrating probability and cross section of the Li+-C60 encapsulation process
      through an ab initio molecular dynamics investigation.
AB  - The endohedral complex system of Li+-C60 has been shown to possess interesting
      applications in photovoltaics, supramolecular chemistry, and functionalized
      materials. In this study, we perform a theoretical investigation of Li+
      encapsulation within a C60 cage by employing an ab initio molecular dynamics
      approach. The Li+ cation is positioned 9 A away from the C60 center of mass, and
      fired towards a randomized spot in a six-membered ring with a certain level of
      inletting energy, which is 7.5 eV, 9 eV, 12 eV, or 15 eV. In total, 2000 samples
      of MD trajectories are investigated. Our statistical results yielded a
      penetrating probability in the range of 0.8% to 15.6% with respect to the above
      inletting energy, while the cross section ranges from 0.006 A2 to 0.123 A2.
      Moreover, we observed that the penetrating probability exhibited direct
      proportionality to the inletting energy. Hence, we can determine that the minimum
      required inletting energy for reaction occurrence is 6.6 eV. Overall, it seems
      difficult for Li+ to penetrate through the sp2-carbon wall, because a very high
      inletting energy is required to open the entrance. At the same time, Li+ must
      approach closely to the center of a six-membered ring to enhance the penetration
      probability.

PMID- 29468228
TI  - Two cases of differentiation syndrome with ocular manifestations in patients with
      acute promyelocytic leukaemia treated with all-trans retinoic acid and arsenic
      trioxide.
AB  - Purpose: To describe two cases of differentiation syndrome presenting with ocular
      manifestations including bilateral chorioretinopathy in patients with acute
      promyelocytic leukaemia treated with all-trans retinoic acid and arsenic trioxide
      differentiation therapy. Observations: This observational case series identifies
      two patients at a single tertiary institution diagnosed with differentiation
      syndrome with associated ophthalmic involvement. Both patients reported bilateral
      reduction in visual acuity at days fourteen and ten respectively following
      initiation of differentiation therapy in addition to developing other systemic
      manifestations of differentiation syndrome. Both patients received the same
      chemotherapeutic regimen including both all-trans retinoic acid and arsenic
      trioxide as well as ten days of routine differentiation syndrome prophylaxis with
      oral prednisolone. Case 1 presented with bilateral pale yellow sub-retinal
      lesions concentrated at the posterior poles with ocular coherence tomography
      (OCT) evidence of bilateral multifocal areas of focal RPE elevation and adhesion
      to the thickened outer retina with interspersed sub-retinal fluid. Fluorescein
      angiography revealed areas of early hyperflouresence corresponding to the yellow
      chorioretinal lesions with late diffuse leakage of fluid into the subretinal
      space. Case 2 presented with a similar characteristic retinal findings on
      fundoscopy and optical coherence tomography. Both patients experienced rapid
      improvement in the visual symptoms and marked resolution of the sub-retinal fluid
      within seven to fourteen days of onset with excellent long-term visual outcome.
      Both patients achieved molecular remission after induction and received standard
      consolidation and maintenance therapy without visual disturbance. Conclusion and
      importance: Ocular manifestations of differentiation syndrome have been only
      recently recognised. We present a case series of two patients with
      differentiation syndrome with ocular involvement. Common to both presentations
      was the presence of bilateral reduction in visual acuity with multifocal serous
      retinal detachment secondary to chorioretinopathy. The visual outcome from both
      presentations was excellent with rapid normalisation of visual acuity and
      resolution of the sub-retinal fluid with only the first case having their
      differentiation therapy temporarily withheld during the acute phase of illness.

PMID- 29468230
TI  - Simulation of colony pattern formation under differential adhesion and cell
      proliferation.
AB  - Proliferation of individual cells is one of the hallmarks of living systems, and
      collectively the cells within a colony or tissue form highly structured patterns,
      influencing the properties at the population level. We investigate the joint
      effect of proliferation in the form of cell division and cell sorting due to
      differential adhesion using a cellular automaton model. Through simulations and
      theoretical analysis akin to interface growth, we show that this model gives rise
      to slower than exponential growth in the case of a single cell type as well as
      novel colony patterns in the case of two cell types. In particular, engulfment of
      one cell type by the other is strongly enhanced compared to the prediction from
      the differential adhesion hypothesis in the absence of proliferation. These
      observations provide new insights in predicting and characterizing colony
      morphology using experimentally accessible information such as single cell growth
      rate and cell adhesion strength.

PMID- 29468231
TI  - Copper-catalyzed decarboxylative regioselective synthesis of 1,5-disubstituted
      1,2,3-triazoles.
AB  - A copper-catalyzed decarboxylative regioselective protocol for the synthesis of
      1,5-disubstituted 1,2,3-triazoles through direct annulation of cinnamic acids
      with aryl azides has been developed. This is the first example of 1,5
      disubstituted 1,2,3-triazoles, under aerobic conditions using Cu(ii) as the
      catalyst, which were generally synthesized using a ruthenium(ii) catalyst. The
      simplicity and regioselectivity of this methodology, complementing to the
      classical CuAAC catalyzed the synthesis of 1,4-disubstituted 1,2,3-triazoles.

PMID- 29468232
TI  - The (photo)chemistry of Stenhouse photoswitches: guiding principles and system
      design.
AB  - Molecular photoswitches comprise chromophores that can be interconverted
      reversibly with light between two states with different photochemical and
      physicochemical properties. This feature renders them useful for diverse
      applications, ranging from materials science, biology (specifically
      photopharmacology) to supramolecular chemistry. With new and more challenging
      systems to control, especially extending towards biomedical applications, using
      visible or near-infrared light for photoswitch activation becomes vital. Donor
      acceptor Stenhouse adducts are a novel class of visible light-responsive negative
      photochromes that provide a possible answer to current limitations of other
      photoswitch classes in the visible and NIR window. Their rapid development since
      their discovery in 2014, together with first successful examples of applications,
      demonstrate both their potential and areas where improvements are needed. A
      better understanding of DASA characteristics and its photoswitching mechanism has
      revealed that they are in fact a subset of a more general structural class of
      photochromes, namely Stenhouse photoswitches. This tutorial review aims at
      providing an introduction and practical guide on DASAs: it focuses on their
      structure and synthesis, provides fundamental insights for understanding their
      photoswitching behavior and demonstrates guiding principles for tailoring these
      switches for given applications.

PMID- 29468233
TI  - Two-dimensional Fe3O4/MoS2 nanocomposites for a magnetorheological fluid with
      enhanced sedimentation stability.
AB  - Superparamagnetic Fe3O4 nanoparticles were successfully deposited on the surface
      of MoS2 nanosheets (Fe3O4/MoS2) by a sonochemical method and the obtained
      Fe3O4/MoS2 nanocomposites were used as a promising candidate for a
      magnetorheological (MR) fluid. This MR fluid was prepared from the Fe3O4/MoS2
      nanocomposites and its corresponding MR performances were examined using a
      rotational rheometer. The MR fluid based on Fe3O4/MoS2 showed typical MR effects
      with increasing viscosity, shear stress, yield stress and dynamic shear modulus
      depending on the applied magnetic fields. Compared with commercial carbonyl iron
      (CI) particles, the sedimentation stability of the Fe3O4/MoS2-MR fluid was
      greatly improved because of its unique two-dimensional structure and the reduced
      fluid-particle density mismatch. Therefore, the prepared Fe3O4/MoS2-based MR
      fluid with typical MR effects and good sedimentation stability would have great
      potential in practical applications.

PMID- 29468238
TI  - Carbodiphosphorane-based nickel pincer complexes and their (de)protonated
      analogues: dimerisation, ligand tautomers and proton affinities.
AB  - The reactivity patterns of carbodiphosphoranes (CDPs) as ligands are much less
      explored than those of isoelectronic analogues. In the current manuscript, we
      investigate the reactivity of the carbodiphosphorane-based PCP nickel(ii) pincer
      complex [({dppm}2C)NiCl]Cl (1) towards acids and bases, calculate proton
      affinities, analyse the bonding situation and tautomeric forms with the aim to
      evaluate whether CDPs can potentially act as cooperative ligands in catalysis
      (dppm = 1,1-bis(diphenylphosphino)methane). Our investigations show that
      different tautomeric forms are stable for the coordinated and the uncoordinated
      ligand. The protonated CDP-based complex 2 represents a rare example of a
      cationic donor group binding to a cationic metal centre. The continuous arm
      deprotonation of 1 leads to the formation of remarkably stable dimers with Ni-C-P
      C-metallacycles. In comparison to corresponding boron and amine-based ligands,
      the coordinated CDP-group exhibits the lowest proton affinity according to DFT
      calculations, indicating that coordinated CDP ligands can potentially serve as
      proton relay in cooperative catalysis.

PMID- 29468239
TI  - Living ring-opening polymerization of epsilon-caprolactone catalyzed by beta
      quinolyl-enamino aluminium complexes: ligand electronic effects.
AB  - A series of beta-quinolyl-enamino aluminium complexes [AlLMe2] 1-7 {L = [(2
      C9H6N)-CH[double bond, length as m-dash]C(4-MeC6H4)-N(Ar)-], Ar = C6H5 (1), 4
      FC6H4 (2), 3,4,5-F3C6H2 (3), C6F5 (4), 5-tBuC6H4 (5), 2,6-Me2C6H3 (6), and 2,6
      iPr2C6H3 (7)} were synthesized by the reaction of AlMe3 with the corresponding
      beta-quinolyl-enamine ligands. All the complexes were characterized by 1H and 13C
      NMR spectroscopy and elemental analysis. The molecular structures of complexes 1
      3 and 7 were confirmed by single-crystal X-ray diffraction, which revealed that
      all the Al atoms adopt a distorted tetrahedral geometry. These Al complexes were
      tested as the initiators for the ring-opening polymerization (ROP) of epsilon
      caprolactone (epsilon-CL). The polymerization results showed that 1-5 in the
      presence of BnOH proceeded efficiently and their catalytic behaviors toward the
      ROP of epsilon-CL were significantly affected by the substituents of the aryl
      ring (Ar) on the end of the enamino framework, where the placement of electron
      withdrawing substituents caused higher catalytic activity. However 6 and 7
      displayed poor activity under the same conditions, suggesting that ortho
      substituents on the Ar moieties hamper the coordination-insertion of the epsilon
      CL monomer. The ROP of epsilon-CL by efficient binary catalytic systems proceeded
      in a living manner evidenced by the narrow PDIs and the linear nature of Mnversus
      conversion plots and monomer/catalyst ratios.

PMID- 29468240
TI  - Water structure and dynamics in the hydration layer of a type III anti-freeze
      protein.
AB  - We report on a molecular dynamics study on the relation between the structure and
      the orientational (and hydrogen bond) dynamics of hydration water around the
      ocean pout AFP III anti-freeze protein. We find evidence for an increasing
      tetrahedral structure from the area opposite to the ice binding site (IBS)
      towards the protein IBS, with the strongest signal of tetrahedral structure
      around the THR-18 residue of the IBS. The tetrahedral structural parameter mostly
      positively correlates with increased reorientation decay times. Interestingly,
      for several key (polar) residues that are not part of the IBS but are in its
      vicinity, we observe a decrease of the reorientation time with increasing
      tetrahedral structure. A similar anti-correlation is observed for the hydrogen
      bonded water molecules. These effects are enhanced at a lower temperature. We
      interpret these results in terms of the structure-making and structure-breaking
      residues. Moreover, we investigate the tetrahedral structure and dynamics of
      waters at a partially dehydrated IBS, and for the protein adsorbed at the air
      water interface. We find that the mutation changes the preferred protein
      orientation upon adsorption at an air-water interface. These results are in
      agreement with the water-air Vibration Sum Frequency Generation spectroscopic
      experiments showing a strongly reduced tetrahedral signal upon mutation at the
      IBS.

PMID- 29468241
TI  - Polymer brushes in solid-state nanopores form an impenetrable entropic barrier
      for proteins.
AB  - Polymer brushes are widely used to prevent the adsorption of proteins, but the
      mechanisms by which they operate have remained heavily debated for many decades.
      We show conclusive evidence that a polymer brush can be a remarkably strong
      kinetic barrier towards proteins by using poly(ethylene glycol) grafted to the
      sidewalls of pores in 30 nm thin gold films. Despite consisting of about 90%
      water, the free coils seal apertures up to 100 nm entirely with respect to serum
      protein translocation, as monitored label-free through the plasmonic activity of
      the nanopores. The conclusions are further supported by atomic force microscopy
      and fluorescence microscopy. A theoretical model indicates that the brush
      undergoes a morphology transition to a sealing state when the ratio between the
      extension and the radius of curvature is approximately 0.8. The brush-sealed
      pores represent a new type of ultrathin filter with potential applications in
      bioanalytical systems.

PMID- 29468242
TI  - Electronic structure of dipeptides in the gas-phase and as an adsorbed monolayer.
AB  - Peptide-based molecular electronic devices are promising due to the large
      diversity and unique electronic properties of biomolecules. These electronic
      properties can change considerably with peptide structure, allowing diverse
      design possibilities. In this work, we explore the effect of the side-chain of
      the peptide on its electronic properties, by using both experimental and
      computational tools to detect the electronic energy levels of two model peptides.
      The peptides include 2Ala and 2Trp as well as their 3-mercaptopropionic acid
      linker which is used to form monolayers on an Au surface. Specifically, we
      compare experimental ultraviolet photoemission spectroscopy measurements with
      density functional theory based computational results. By analyzing differences
      in frontier energy levels and molecular orbitals between peptides in gas-phase
      and in a monolayer on gold, we find that the electronic properties of the peptide
      side-chain are maintained during binding of the peptide to the gold substrate.
      This indicates that the energy barrier for the peptide electron transport can be
      tuned by the amino acid compositions, which suggests a route for structural
      design of peptide-based electronic devices.

PMID- 29468243
TI  - Improved mass spectrometric detection of acidic peptides by variations in the
      functional group pKa values of reverse micelle extraction agents.
AB  - Polymeric reverse micelles can be used to selectively extract peptides from
      complex mixtures via a two-phase extraction approach. In previous work, we have
      shown that the charge polarity of the hydrophilic functional group that is in the
      interior of the reverse micelle dictates the extraction selectivity. To
      investigate how the extraction is influenced by the inherent pKa of the
      functional group, we designed and tested a series of polymeric reverse micelles
      with variations in the hydrophilic functional group. From this series of
      polymers, we find that the extraction capability of the reverse micelles in an
      apolar phase is directly related to the aqueous phase pKa of the interior
      functional group, suggesting that the functional groups maintain their inherent
      chemistry even in the confined environment of the reverse micelle interior.
      Because these functional groups maintain their inherent pKa in the reverse
      micelle interior, they provide predictable extraction selectivity upon changes in
      aqueous phase pH. We exploit this finding to demonstrate that sulfonate
      containing polymers can be used to remove basic peptides from complex mixtures,
      thereby allowing the improved detection of acidic peptides. Using these new
      materials, we also demonstrate a new means of isoelectric point (pI) bracketing
      that allows the mass spectrometric detection of peptides with a defined and
      narrow range of pI values.

PMID- 29468244
TI  - A self-template synthesis of defect-rich WS2 as a highly efficient
      electrocatalyst for the hydrogen evolution reaction.
AB  - Defect-rich tungsten disulfide (WS2) nanosheets are synthesized via a self
      template method, in which tungsten oxide is partially sulfurized to form WS2/WO3
      nanosheets. The defect-rich WS2 nanosheets only require an overpotential of 145
      mV to achieve a current density of 10 mA cm-2 with a Tafel slope of 58.5 mV dec-1
      and exhibit excellent stability in 0.5 M H2SO4 electrolyte.

PMID- 29468245
TI  - Protonation-induced ultrafast torsional dynamics in 9-anthrylbenzimidazole: a pH
      activated molecular rotor.
AB  - We report the photophysical properties and excited state dynamics of 9
      anthrylbenzimidazole (ANBI) which exhibits protonation-induced molecular rotor
      properties. In contrast to the highly emissive behavior of neutral ANBI,
      protonation of the benzimidazole group of ANBI induces efficient nonradiative
      deactivation by ultrafast torsional motion around the bond connecting the
      anthracene and benzimidazole units, as revealed by ultrafast transient absorption
      and fluorescence spectroscopy. Contrary to viscosity-independent fluorescence of
      neutral dyes, protonated ANBI is shown to display linear variation of emission
      yield and lifetime with solvent viscosity. The protonation-induced molecular
      rotor properties in the studied system are shown to be driven by enhanced charge
      transfer and are corroborated by quantum chemical calculations. Potential
      application as a microviscosity sensor of acidic regions in a heterogeneous
      environment by these proton-activated molecular rotor properties of ANBI is
      discussed.

PMID- 29468255
TI  - Letter to the editor.

PMID- 29468256
TI  - Intestinal Barrier Impairment and Immune Activation in HIV-Infected Advanced Late
      Presenters are Not Dependent on CD4 Recovery.
AB  - Damage of the mucosal barrier in HIV infection, microbial translocation, and
      immune activation can persist even in patients on successful antiretroviral
      therapy (ART) especially advanced late presenters. The aim of this study was to
      find factors that determine immune activation and bacterial translocation in HIV
      infected advanced late presenters on suppressive ART. Forty-three late presenters
      (CD4 < 200 cells/ul prior to ART) on successful ART (more than 2 years of ART)
      with optimal and suboptimal CD4 recovery were enrolled into this study. The serum
      concentrations of intestinal fatty acid-binding peptide (I-FABP), zonulin-1,
      programmed cell death-1 protein (PCDP-1), and soluble (s)CD14 were measured using
      the ELISA test. We found higher serum levels of I-FABP and sCD14 in successfully
      antiretroviral-treated advanced late presenters compared to healthy subjects (p <
      0.0001 and p = 0.0004). The serum concentration of PCDP-1 and zonulin-1 in HIV
      infected patients did not differ from healthy controls. The levels of microbial
      translocation and immune activation markers were not associated with the degree
      of CD4 recovery. A serum concentration of I-FABP above 2.03 ng/ml was
      independently associated with a shorter ART (OR 0.78; p = 0.03). Older age was
      related to serum levels of sCD14 above 2.35 ug/ml (OR 1.1; p = 0.01). Higher
      serum levels of I-FABP and sCD14 in successfully antiretroviral-treated advanced
      late presenters compared to healthy subjects suggest an incomplete reconstruction
      of the intestinal barrier and sustained immune activation despite good CD4
      recovery. It was not the CD4 level, but the length of the suppressive ART that
      was found to be associated with the restoration of the intestinal barrier.

PMID- 29468258
TI  - Intermuscular implantation technique for subcutaneous cardioverter
      defibrillators.
AB  - BACKGROUND: The conventional technique for subcutaneous implantable cardioverter
      defibrillator (S-ICD) implantation has been associated with pocket complications.
      The aim of this study was to evaluate the efficacy and safety of an alternative
      intermuscular technique for S-ICD implantation. METHODS: S-ICDs were implanted in
      ten consecutive patients (ten males, mean age: 46.8 +/- 14.7 years). The pocket
      for the pulse generator was made above the serratus anterior muscular fascia and
      beneath the latissimus dorsi muscle by detaching the fibrous tissue between the
      muscles. Electrode implantation was performed using the three- (n = 4) or the two
      incision technique (n = 6). RESULTS: All S-ICDs were successfully implanted in
      the absence of any procedure-related complications with a successful 65-J
      standard polarity defibrillation threshold testing, apart from one patient with
      Brugada syndrome who needed device repositioning more dorsally. During a mean
      follow-up of 16.5 +/- 7.3 months, no major complications requiring surgical
      repair were encountered, while patients demonstrated high levels of comfort and
      satisfaction with the cosmetic result. One patient experienced an inappropriate
      shock due to noise detection, which was resolved after reprogramming to a
      different sensing vector. CONCLUSION: The intermuscular technique is a safe and
      efficacious approach for S-ICD implantation. This technique could lead to fewer
      pocket-related complications and better cosmetic results.

PMID- 29468259
TI  - Palliative care in heart failure : A meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Palliative care can play an important role in the management of heart
      failure. We conducted a systematic review and meta-analysis to compare the
      efficacy and safety of palliative care in patients with heart failure. METHODS:
      PubMed, Embase, Web of Science, EBSCO, and the Cochrane Library databases were
      systematically searched. Randomized controlled trials (RCTs) on the impact of
      palliative care on heart failure were included. Two investigators independently
      searched the articles, extracted data, and assessed the quality of included
      studies. The primary outcome was mortality. RESULTS: Seven RCTs were included in
      the meta-analysis. Compared with usual care for heart failure, palliative care
      was associated with a significantly increased quality of life (standardized mean
      difference = 1.46; 95% confidence interval [CI] = 0.12 to 2.79; p = 0.03) and
      reduced depression scores (standardized mean difference = -0.62; 95% CI = -0.99
      to -0.25; p = 0.03), but demonstrated no impact on mortality (risk ratio [RR] =
      1.28; 95% CI = 0.86 to 1.92; p = 0.22) and rehospitalization (RR = 0.84; 95% CI =
      0.66 to 1.07; p = 0.16). CONCLUSION: Palliative care can improve the quality of
      life and reduce the occurrence of depression in patients with heart failure.

PMID- 29468257
TI  - Aurora kinase B regulates axonal outgrowth and regeneration in the spinal motor
      neurons of developing zebrafish.
AB  - Aurora kinase B (AurkB) is a serine/threonine protein kinase with a well
      characterised role in orchestrating cell division and cytokinesis, and is
      prominently expressed in healthy proliferating and cancerous cells. However, the
      role of AurkB in differentiated and non-dividing cells has not been extensively
      explored. Previously, we have described a significant upregulation of AurkB
      expression in cultured cortical neurons following an experimental axonal
      transection. This is somewhat surprising, as AurkB expression is generally
      associated only with dividing cells Frangini et al. (Mol Cell 51:647-661, 2013);
      Hegarat et al. (J Cell Biol 195:1103-1113, 2011); Lu et al. (J Biol Chem
      283:31785-31790, 2008); Trakala et al. (Cell Cycle 12:1030-1041, 2014). Herein,
      we present the first description of a role for AurkB in terminally differentiated
      neurons. AurkB was prominently expressed within post-mitotic neurons of the
      zebrafish brain and spinal cord. The expression of AurkB varied during the
      development of the zebrafish spinal motor neurons. Utilising pharmacological and
      genetic manipulation to impair AurkB activity resulted in truncation and aberrant
      motor axon morphology, while overexpression of AurkB resulted in extended axonal
      outgrowth. Further pharmacological inhibition of AurkB activity in regenerating
      axons delayed their recovery following UV laser-mediated injury. Collectively,
      these results suggest a hitherto unreported role of AurkB in regulating neuronal
      development and axonal outgrowth.

PMID- 29468260
TI  - Superficial Siderosis and Dural Ectasia in a Patient with Marfan Syndrome.

PMID- 29468261
TI  - In Vivo Molecular Profiling of Human Glioma : Cross-Sectional Observational Study
      Using Dynamic Susceptibility Contrast Magnetic Resonance Perfusion Imaging.
AB  - PURPOSE: To assess the diagnostic performance of dynamic susceptibility contrast
      perfusion magnetic resonance perfusion imaging (DSC-MRI) for in vivo human glioma
      molecular profiling. METHODS: In this study 100 patients with histopathologically
      confirmed glioma who provided written informed consent were retrospectively
      assessed between January 2016 and February 2017 in two prospective trials that
      were approved by the local institutional review board. Cerebral blood volume
      (CBV) measurements from DSC-MRI were assessed, and histogram parameters of
      relative CBV (rCBV) results were compared among World Health Organization (WHO)
      2016 based histological findings and molecular characteristics. A classification
      and regression tree (CART) algorithm with 10-fold cross-validation was used to
      calculate the diagnostic accuracy. RESULTS: The 90th percentile (C90) of rCBV was
      significantly lower in patients with the isocitrate dehydrogenase 1/2 (IDH1/2)
      mutation (2.86 +/- 1.21; p < 0.001) and loss of alpha-thalassemia mental
      retardation syndrome X-linked (ATRX) expression (2.23 +/- 0.91; p < 0.001) than
      in those with the IDH1/2 wild type (4.78 +/- 2.34) and maintained ATRX expression
      (4.30 +/- 2.02). The standard deviation (SD) of rCBV was significantly higher in
      glioblastoma (GBM) with methylated O6-methylguanine DNA methyltransferase (MGMT;
      1.99 +/- 0.73; p = 0.001) than in those with unmethylated MGMT (1.20 +/- 0.45).
      In CART analysis, rCBV predicted the molecular subgroup in 76.3% of astroglial
      tumors; however, the diagnostic performance was reduced to 48.1% by including
      oligodendrogliomas with chromosome 1p/19q co-deletion in the analysis due to
      substantial overlap of rCBV values between OD1p/19q-LOH and IDHwt GBM.
      CONCLUSION: The DSC-MRI procedure may provide insight into the IDH1/2 mutation
      and ATRX expression status and MGMT methylation profile of diffuse glioma;
      however, taking integrated oligodendroglioma into account limits the diagnostic
      performance of rCBV in non-invasively predicting the molecular subtype.

PMID- 29468263
TI  - Assessment of Detection Methods and Vegetation Associations for Introduced
      Finlayson's Squirrels (Callosciurus finlaysonii) in Italy.
AB  - Managing biological invasions requires rapid, cost-effective assessments of
      introduced species' occurrence, and a good understanding of the species'
      vegetation associations. This is particularly true for species that are elusive
      or may spread rapidly. Finlayson's squirrel (Callosciurus finlaysonii) is native
      to Thailand and southeastern Asia, and two introduced populations occur in
      peninsular Italy. One of the two introduced populations is rapidly expanding, but
      neither effective monitoring protocols nor reliable information on vegetation
      associations are available. To fill this gap, we conducted visual surveys and
      hair tube sampling in a periurban landscape of southern Italy to compare the
      effectiveness of these two methods in assessing presence of Finlayson's squirrel.
      We also determined the species' association with vegetation types at detection
      locations and nesting sites. Both visual and hair tube sampling effectively
      assessed the species' presence, but hair tubes resulted in fewer false absences.
      Moreover, when we controlled for the costs of labor and equipment, hair tubes
      were 33.1% less expensive than visual sampling. Presence of squirrels and their
      nests was positively correlated with shrub species richness, indicating that the
      occurrence of forests with well-developed understory may inhibit the spread of
      the species.

PMID- 29468262
TI  - A Consensus-Based Criterion Standard for the Requirement of a Trauma Team.
AB  - BACKGROUND: Trauma team activation (TTA) represents a considerable expenditure of
      trauma centre resources. It is mainly triggered by field triage criteria. The
      overall quality of the criteria may be evaluated based on the rate of over- and
      undertriage. However, there is no gold standard that defines which adult patients
      truly require a trauma team. The objective of this study was to develop consensus
      based criteria defining the necessity for a trauma team. METHODS: A consensus
      group was formed by trauma specialists experienced in emergency and trauma care
      with a specific interest in field triage and having previously participated in
      guideline development. A literature search was conducted to identify criteria
      that have already been used or suggested. The initial list of criteria was
      discussed in two Delphi round and two consensus conferences. The entire process
      of discussion and voting was highly standardized and extensively documented,
      resulting in a final list of criteria. RESULTS: Initially 95 criteria were
      identified. This was subsequently reduced to 20 final criteria to appropriately
      indicate the requirement for attendance of a trauma team. The criteria address
      aspects related to injury severity, admission to an intensive care unit, death
      within 24 h, need for specified invasive procedures, need for surgical and/or
      interventional radiological procedures, and abnormal vital signs within a defined
      time period. CONCLUSIONS: The selected criteria may be applied as a tool for
      research and quality control concerning TTA. However, future studies are
      necessary to further evaluate for possible redundancy in criteria that may allow
      for further reduction in criteria.

PMID- 29468264
TI  - The accuracy of free hand resection in limb salvage surgery of bone tumours.
AB  - PURPOSE: Resection length should be designed before limb salvage surgery of bone
      tumours. The aim of this study was to evaluate the accuracy of free hand
      resections. METHODS: Two hundred forty-eight cases were enrolled, including 173
      osteosarcomas, 24 giant cell tumours, 16 chondrosarcomas, seven spindle cell
      sarcomas, 14 bone metastases, three undifferentiated pleomorphic sarcomas, three
      Ewing sarcomas, two angiosarcomas, and six other bone and soft tissue tumours.
      One hundred forty-six were located in the femur, 75 in the tibia, 19 in the
      humerus, six in the radius, one in the ulna, and one in the fibula. The resection
      length was included in the pre-operative plan. After surgery, we measure the
      length of specimens. Both lengths were compared. The patients were classified by
      tumour location. RESULTS: The range of length difference was from - 21 to 29 mm.
      The mean absolute value of the differences was 8.0 +/- 6.3 mm. Altogether, 173
      cases (69.8%) had an absolute difference value of <= 10 mm, 66 cases (26.6%) of
      10-20 mm, and only 9 cases (3.6%) of > 20 mm. The average length of gross
      specimens (164.1 +/- 43.3 mm) was longer than planned lengths (160.7 +/- 44.2
      mm); p < 0.001. CONCLUSIONS: The differences were significant in the distal femur
      and proximal tibia. Even though, the accuracy of free hand resection is
      acceptable in this method.

PMID- 29468265
TI  - The tridimensional geometry of the proximal femur should determine the design of
      cementless femoral stem in total hip arthroplasty.
AB  - PURPOSE: Using a cementless femoral stem in total hip arthroplasty (THA), optimal
      filling of the proximal femoral metaphyseal volume (PFMV) and restoration of the
      extramedullary proximal femoral (PF) parameters (i.e., femoral offset (FO), neck
      length (FNL), and head height (FHH)) constitute key goals for optimal hip
      biomechanics, functional outcome, and THA survivorship. However, almost 30% of
      mismatch between the PF anatomy and implant geometry of the most widely implanted
      non-modular cementless femoral stem has been demonstrated in a computed
      tomography scan (CT scan) study. Therefore, this anatomic study aimed to evaluate
      the relationship between the intra- and extramedullary PF parameters using
      tridimensional CT scan reconstructions. METHODS: One hundred fifty-one CT scans
      of adult healthy hips were obtained from 151 male Caucasian patients (mean age =
      66 +/- 11 years) undergoing lower limb CT scan arteriography. Tridimensional PF
      reconstructions and parameter measurements were performed using a corrected PF
      coronal plane-defined by the femoral neck and diaphyseal canal longitudinal axes
      to avoid influence of PF helitorsion and femoral neck version on extramedullary
      PF parameters. RESULTS: Independently of the femoral neck-shaft angle, the PFMV
      was significantly and positively correlated with the FO, FNL, and FHH (r = 0.407
      to 0.420; p < 0.0001). CONCLUSION: This study emphasized that the tridimensional
      PF geometry measurement in the corrected coronal plane of the femoral neck can be
      useful to determine and optimize the design of a non-modular cementless femoral
      stem. Particularly, continuous homothetic size progression of the intra- and
      extramedullary PF parameters should be achieved to assure stem fixation and
      restore anatomic hip biomechanics.

PMID- 29468266
TI  - Bilateral patterns and motor function of the extralaryngeal branching of the
      recurrent laryngeal nerve.
AB  - PURPOSE: To evaluate the bilateral patterns and motor function of the
      extralaryngeal branches (ELB) of the recurrent laryngeal nerve(RLN). METHODS:
      This study included 500 consecutive patients who underwent total thyroidectomy.
      Intraoperative nerve monitoring (IONM) was used in 230 patients. Demographic
      data, indications for surgery, the bilateral patterns of ELB of the RLN,
      electromyographic activity of the ELB, distance between the branching point to
      the entrance into the larynx, and the rate of postoperative morbidity were
      analyzed. RESULTS: The overall rate of ELB was 27.6% (276/1000). A single trunk
      of the RLN on both sides was found in 269 (54%) patients, whereas ELB on both
      sides was observed in 45 (9%) patients. The rates of ELB on the left and right
      sides were 26.6 and 28.6%, respectively. Of the 89 branched nerves which were
      dissected using IONM, an evoked motor response was present in 100% of the
      anterior branches and 5.6% of the posterior branches. The mean branching distance
      of the RLN was significantly greater in female patients than in male patients on
      the left side (p = 0.031). The patterns of ELB showed no significant difference
      in male and female patients. The rates of postoperative transient and permanent
      hypoparathyroidism and unilateral RLN palsy were 21.6 and 2.8%, and 3.2 and 0.8%,
      respectively. The rate of RLN palsy was higher in branched nerves compared to
      those with a single trunk (0.75 vs 0.3%; p = 0.2). CONCLUSION: Unilateral ELB of
      the RLN might be observed in approximately 1/4 of the patients, while bilateral
      branching is rare. A few number of posterior branches of the RLN can have motor
      function. The RLN's with ELB might have a higher risk of injury compared to those
      with a single trunk.

PMID- 29468268
TI  - ?

PMID- 29468267
TI  - A congenital accessory skin appendage of the nasal columella and nostril sill: a
      rare anatomical variation.
AB  - PURPOSE: An accessory skin appendage of the nasal columella and nostril sill is
      an extremely rare congenital anatomical malformation; only a single case has been
      reported in the literature. However, no pathophysiology has been proposed. The
      purpose of this study is to present a review of the anatomical distribution of
      accessory skin appendages and provide a comprehensive review of their
      pathophysiology based on embryological development. METHODS: We present four
      cases of a protruding skin appendage of the nasal columella or nostril sill. All
      lesions were present from birth with no family history of skin appendages. Three
      patients underwent surgical excision under local anesthesia. RESULTS: The lesions
      were located at the upper and lower lateral borders of the nasal columella and
      the medial and lateral borders of the nostril sill. There has been no sign of
      recurrence over a mean follow-up of 11 months. CONCLUSIONS: Any obstacle or
      injury during the migration process of embryonic development may result in
      maldevelopment. If an obstacle or injury occurs during the medial migration of
      the medial nasal process, congenital polypoid remnant tissue may remain along the
      migration route, resulting in an accessory skin appendage of the nasal columella.
      The location of the accessory columellas ranged from the nostril sill to the soft
      triangle along the anterior border of the medial crus of the alar cartilage.
      These anatomical distributions correspond exactly to the migration route of the
      medial nasal process during embryonic development. We believe that it supports
      our suggested pathophysiology.

PMID- 29468269
TI  - Race Differences in Gastrostomy Tube Placement After Stroke in Majority-White,
      Minority-Serving, and Racially Integrated US Hospitals.
AB  - We sought to determine individual and system contributions to race disparities in
      percutaneous endoscopic gastrostomy (PEG) tube placement after stroke. Ischemic
      stroke admissions were identified from the Nationwide Inpatient Sample between
      2007 and 2011. Hospitals were categorized based on the percentage of
      ethnic/racial minority stroke patients (< 25% ethnic/racial minorities ["majority
      white hospitals"], 25-50% ethnic/racial minorities ["racially integrated
      hospitals"], or > 50% ethnic/racial minorities ["minority-serving hospitals"]).
      Logistic regression was used to evaluate the association between ethnicity/race
      and PEG utilization within and between the different hospital strata. Among
      246,825 stroke admissions, patients receiving care in minority-serving hospitals
      had higher odds of PEG compared to patients in majority-white hospitals,
      regardless of individual patient race (adjusted odds ratio [OR] 1.24, 95% CI 1.12
      1.38). Ethnic/racial minorities had higher odds of PEG than whites in any
      hospital strata; however, this discrepancy was largest in majority-white
      hospitals (OR 1.62, 95% CI 1.48-1.76), and smallest in minority-serving hospitals
      (OR 1.22, 95% CI 1.11-1.33; p for interaction < 0.001). Ethnic/racial minority
      patients had similar odds of PEG in any hospital strata, while white patients had
      increasing odds of PEG in racially integrated and minority-serving compared to
      majority-white hospitals (OR 1.28, 95% CI 1.15-1.43 in racially integrated, and
      OR 1.39, 95% CI 1.23-1.57 in minority-serving, compared to majority-white
      hospitals, p for trend < 0.001). The likelihood of PEG after ischemic stroke was
      increased in minority-serving compared to majority-white hospitals. White
      patients had higher odds of PEG in minority-serving compared to majority-white
      hospitals, indicating a systemic difference in PEG placement across hospitals.

PMID- 29468270
TI  - Unplanned readmission after hospital discharge in burn patients in Iran.
AB  - INTRODUCTION: Burns are considered as one of the most serious health problems
      throughout the world. They may lead to adverse consequences and outcomes. One of
      these outcomes is unplanned readmission. Unplanned readmission has been commonly
      used as a quality indicator by hospitals and governments. This study aimed to
      determine the predictors of unplanned readmission in patients with burns
      hospitalized in a burn center in the North of Iran (Guilan province, Rasht).
      METHODS: This retrospective analytic study has been done on the medical records
      of hospitalized patients with burns in Velayat Sub-Specialty Burn and Plastic
      Surgery Center, Rasht, Iran during 2008-2013. In general, 703 medical records
      have been reviewed but statistical analysis was performed on 626 medical records.
      All data were entered in SPSS (version 16) and analyzed by descriptive and
      inferential statistics. RESULTS: Among 626 patients with burns, the overall
      readmission rate was 5.1%. Predictors of readmission included total body surface
      area (OR 1.030, CI 1.011-1.049), hypertension (OR 2.923, CI 1.089-7.845) and skin
      graft (OR 7.045, CI 2.718-18.258). CONCLUSION: Considering the outcome,
      predictors following burn have a crucial role in the allocation of treatment cost
      for patients with burns and they can be used as one of the quality indicators for
      health care providers and governments.

PMID- 29468271
TI  - Administrating docetaxel, doxorubicin, and cyclophosphamide as a neoadjuvant
      treatment may decrease lymphedema risk in breast cancer patients.

PMID- 29468272
TI  - Correction to: Endoscopic and surgical management of nonampullary duodenal
      neoplasms.
AB  - This article was updated to correct the author listing for Carlos Roberto Simons
      Linares.

PMID- 29468273
TI  - Evolution, functional differentiation, and co-expression of the RLK gene family
      revealed in Jilin ginseng, Panax ginseng C.A. Meyer.
AB  - Most genes in a genome exist in the form of a gene family; therefore, it is
      necessary to have knowledge of how a gene family functions to comprehensively
      understand organismal biology. The receptor-like kinase (RLK)-encoding gene
      family is one of the most important gene families in plants. It plays important
      roles in biotic and abiotic stress tolerances, and growth and development.
      However, little is known about the functional differentiation and relationships
      among the gene members within a gene family in plants. This study has isolated
      563 RLK genes (designated as PgRLK genes) expressed in Jilin ginseng (Panax
      ginseng C.A. Meyer), investigated their evolution, and deciphered their
      functional diversification and relationships. The PgRLK gene family is highly
      diverged and formed into eight types. The LRR type is the earliest and most
      prevalent, while only the Lec type originated after P. ginseng evolved.
      Furthermore, although the members of the PgRLK gene family all encode receptor
      like protein kinases and share conservative domains, they are functionally very
      diverse, participating in numerous biological processes. The expressions of
      different members of the PgRLK gene family are extremely variable within a
      tissue, at a developmental stage and in the same cultivar, but most of the genes
      tend to express correlatively, forming a co-expression network. These results not
      only provide a deeper and comprehensive understanding of the evolution,
      functional differentiation and correlation of a gene family in plants, but also
      an RLK genic resource useful for enhanced ginseng genetic improvement.

PMID- 29468274
TI  - [Selected otorhinolaryngological symptoms in functional disorders of the upper
      cervical spine and temporomandibular joints].
AB  - This paper discusses otorhinolaryngological symptoms associated with functional
      disorders of the upper cervical spine. Hints aimed to avoid misdiagnoses of cross
      organ otorhinolaryngological symptoms as phobic or psychogenic disorders are
      presented. Clinically relevant neuroanatomical convergence of the upper cervical
      spine (occiput to C3) is fundamental for the interpretation of functional
      otorhinolaryngological symptoms. Based thereon, evidence for the most common
      cervical differential diagnoses of dizziness, tinnitus, dysphagia, and
      craniomandibular dysfunction is presented separately. The corresponding
      therapeutic options and their contraindications are discussed in the concluding
      chapter. The importance of interdisciplinary cooperation in related fields is
      emphasized.

PMID- 29468275
TI  - [The innate immune system in oropharyngeal squamous cell carcinoma : Immune
      modulation by HPV].
AB  - Based on clinical and experimental data, oropharyngeal squamous cell carcinomas
      (OPSCC) associated with human papillomavirus (HPV) have been recognized as a
      distinct entity of head and neck cancers. However, outside of clinical trials,
      HPV status currently has no impact on treatment. The natural replication cycle of
      HPV takes place in epithelial cells, and is thus spatially separated from
      cytotoxic immune cells in the epidermis. Dendritic cells (Langerhans cells, LC),
      however, are frequent in this upper dermal layer. The ability of LC to process
      antigens, migrate, and, ultimately activate T cells is inhibited by the activity
      of the viral oncoproteins (E5-E7). Downregulation of functional human leukocyte
      antigen I (HLA-I) epithelial cell surface expression contributes to LC
      inhibition. However, due to their absence in upper skin layers, corresponding
      activation of natural killer (NK) cells via missing-self recognition is not
      relevant. Genome-wide analyses have revealed specific expression signatures for
      HPV-associated OPSCC that are distinct from HPV-negative cancers. Interestingly,
      aberrations in HLA-I genes were common in HPV-associated OPSCC. Our own findings
      indicate more frequent infiltration of HPV-associated OPSCC by CD56-positive
      (CD56+) NK cells, which might be related to HLA-I downregulation during HPV
      associated carcinogenesis. In patients with OPSCC, CD56 positivity correlates
      with improved prognosis after conventional therapy. This could be evidence for
      HPV-associated OPSCC being especially eligible for novel immune-based therapies
      and an indication that immunological data should be included in the design of
      clinical trials.

PMID- 29468276
TI  - Identification and assessment of frailty in older patients with chronic myeloid
      leukemia and myelofibrosis, and indications for tyrosine kinase inhibitor
      treatment.
AB  - The incidence of cancer, including myeloproliferative neoplasms (MPNs), is
      projected to increase significantly due to the growing proportion of people aged
      > 65 years. These older individuals are a heterogeneous population in terms of
      fitness, comorbidity, and psychological reserve. Therefore, age per se does not
      always provide an accurate indication of condition in patients with cancer.
      Frailty has been proposed as an alternative measure of vulnerability that might
      better indicate which patients can tolerate standard cancer treatment and those
      who may benefit from treatment adjustment. A number of methods can be used to
      assess frailty in older patients with hematological malignancies, including the
      Cardiovascular Health Study Frailty Screening Measure, the FRAIL (Fatigue,
      Resistance, Ambulation, Illnesses, and Loss of weight) questionnaire, the
      Clinical Frailty Scale (CFS), and the Gerontopole Frailty Screening Tool. In
      addition to physical frailty, comorbidity and quality of life should also be
      included in the assessment. Prior to the introduction of tyrosine kinase
      inhibitors (TKIs), age was considered a marker of poor prognosis in patients with
      MPNs. In contrast, data show that age is not necessarily a contraindication for
      TKI use. In CML, the efficacy of TKIs has been shown to be independent of age.
      The JAK1/2 inhibitor ruxolitinib also seems to be effective across a range of
      patient ages. Available data suggest that chronological age itself should not
      necessarily be a contraindication for many new therapies in patients with MPNs,
      and that frailty does provide a better measure of vulnerability. There is a need
      for specific methods to assess frailty in patients with MPNs, particularly the
      context of effective new treatment options, such as TKIs and ruxolitinib.

PMID- 29468277
TI  - [Tinea faciei caused by Nannizzia persicolor : An underdiagnosed dermatophyte?]
AB  - We report on a tinea faciei caused by Nannizzia (N.) persicolor. The 4-year-old
      boy had probably been infected by a guinea pig. Unambiguous infections caused by
      N. persicolor are rarely seen in Germany; however, this zoophilic and geophilic
      dermatophyte may only be rarely identified due to its resemblance to Trichophyton
      (T.) mentagrophytes. Therefore, the diagnostic attributes of N. persicolor and
      its differentiation from T. mentagrophytes are described. Particularly in case of
      contact with rodents, N. persicolor should be kept in mind.

PMID- 29468278
TI  - [Bullosis diabeticorum : Two case studies].
AB  - We report two cases of patients with diabetes mellitus who developed bullae
      measuring 2 cm in diameter on the fingers or toes, which could be classified as
      bullosis diabeticorum after excluding several differential diagnoses that are
      discussed. Bullosis diabeticorum is a rare blister formation located on the
      palmoplantar region, which is mainly observed in the case of diabetic patients.
      The clinical picture is characterized by tense bullae measuring up to 10 cm in
      diameter, containing clear to hemorrhagic fluid. Generally, lesions heal without
      residual scarring, less frequently with residual postinflammatory pigmentation or
      tender scars. On histopathological examination, both intraepidermal and
      subepidermal bullae are found without any significant inflammatory infiltrate.
      The etiopathogenesis of bullosis diabeticorum has not yet been clarified.

PMID- 29468279
TI  - [Epidemiology of penile cancer].
AB  - BACKGROUND: Penile cancer represents a rarity in daily clinical practice.
      OBJECTIVES: The aim is to identify global differences concerning the incidence,
      social and risk factors. METHODS: The past and current epidemiologic literature
      is analyzed concerning incidence rates and risk factors. The latter are discussed
      concerning their potential with regard to disease prevention. RESULTS: Globally,
      incidence rates of penile cancer range from low to nonexistent. Distinct
      differences are found when comparing industrialized countries with emerging and
      developing countries. Phimosis seems to be a crucial risk factor in the formation
      of penile cancer. Additionally, chronic inflammatory diseases of the penis were
      found to be associated with a higher risk. CONCLUSIONS: Preventive measures
      should be considered in relation to the rarity of the disease, especially in the
      valuation of circumcision during early childhood. Regular clinical examination of
      the penis is a sensible measure of early detection.

PMID- 29468280
TI  - [Pathology and histopathological evaluation of penile cancer].
AB  - BACKGROUND: Penile cancer is rare in Germany and in western European countries.
      Our understanding of the pathogenesis and pathology of this malignancy has
      increased considerably in recent years. OBJECTIVES: Clinical management has
      become more complex, with organ-preserving strategies being increasingly favored.
      Associated with these developments, the demands on the pathology reports of
      biopsies and surgical specimens from the penis have also increased. MATERIALS AND
      METHODS: According to guidelines and the relevant literature, this review
      outlines the most important aspects that must be considered in the classification
      and pathological reporting of penile cancer. RESULTS: Correct histological
      subtyping of penile cancer is important for prognostic and therapeutic
      considerations. There are also some peculiarities with the current TNM
      classification system of this tumor compared to other entities. CONCLUSION:
      Handling of specimens and histopathological typing must be performed by
      experienced pathologists according to recent developments in the pathogenesis,
      classification, and therapeutic strategies of penile cancer.

PMID- 29468281
TI  - [Current guideline-oriented follow-up of small renal masses : Applied risk scores
      and future outlook].
AB  - After surgical resection of renal cell carcinoma by laparoscopic or open partial
      or complete nephrectomy, medical aftercare based on the current guidelines should
      be provided. This seems desirable, especially because one third of patients after
      initial curative tumor resection develop recurrence over time. In this article,
      the current recommendations for follow-up will be systematically presented based
      on the accepted German S3 guideline and the European Association of Urology (EAU)
      guideline. Another point of this article will be the presentation of the
      currently applied risk scores to predict prognosis with a focus on molecular
      markers. The goal is to improve the prediction of survival and to facilitate risk
      adjusted aftercare.

PMID- 29468282
TI  - [Standard surgery for small renal masses (<4 cm)].
AB  - BACKGROUND: Several new treatment strategies have emerged in the treatment of
      small renal masses (<4 cm in diameter). Active surveillance and ablative
      techniques have been introduced but it remains unclear which patients will
      benefit the most from these new treatment options. A surgical approach remains
      standard of care. In recent decades, radical nephrectomy has been replaced by
      nephron-sparing surgery for the management of small renal masses. RESULTS: In
      addition to the open partial nephrectomy, which is considered the standard
      approach, the number of surgeries performed using minimally invasive techniques
      is increasing. Recent data show that there might be some benefits such as less
      blood loss. The disadvantages shown by laparoscopic partial nephrectomy such as
      prolonged warm ischemia, longer operation times, and postoperative renal
      impairment might be negligible for the robotic approach. Therefore, current
      guidelines allow these approaches in addition to open partial nephrectomy if
      sufficient surgical expertise is given.

PMID- 29468283
TI  - Activation of Wnt/beta-catenin signaling is involved in hair growth-promoting
      effect of 655-nm red light and LED in in vitro culture model.
AB  - Activation of the Wnt/beta-catenin signaling pathway plays an important role in
      hair follicle morphogenesis and hair growth. Recently, low-level laser therapy
      (LLLT) was evaluated for stimulating hair growth in numerous clinical studies, in
      which 655-nm red light was found to be most effective and practical for
      stimulating hair growth. We evaluated whether 655-nm red light + light-emitting
      diode (LED) could promote human hair growth by activating Wnt/beta-catenin
      signaling. An in vitro culture of human hair follicles (HFs) was irradiated with
      different intensities of 655-nm red light + LED, 21 h7 (an inhibitor of beta
      catenin), or both. Immunofluorescence staining was performed to assess the
      expression of beta-catenin, GSK3beta, p-GSK3beta, and Lef1 in the Wnt/beta
      catenin signaling. The 655-nm red light + LED not only enhanced hair shaft
      elongation, but also reduced catagen transition in human hair follicle organ
      culture, with the greatest effectiveness observed at 5 min (0.839 J/cm2).
      Additionally, 655-nm red light + LED enhanced the expression of beta-catenin, p
      GSK3beta, and Lef1, signaling molecules of the Wnt/beta-catenin pathway, in the
      hair matrix. Activation of Wnt/beta-catenin signaling is involved in hair growth
      promoting effect of 655-nm red light and LED in vitro and therefore may serve as
      an alternative therapeutic option for alopecia.

PMID- 29468284
TI  - Is neutrophil-to-lymphocytes ratio a clinical relevant preoperative biomarker in
      upper tract urothelial carcinoma? A meta-analysis of 4385 patients.
AB  - BACKGROUND: Preoperative blood-based inflammatory biomarkers have been suggested
      to improve staging and prognostication in patients with upper-tract urothelial
      carcinoma (UTUC). Neutrophil-to-lymphocyte ratio (NLR) is the most studied blood
      based biomarker. NLR is an indicator of systemic inflammation and has been shown
      to be associated with a poor prognosis in various malignancies. The aim of this
      study was to analyze the current evidence regarding the prognostic significance
      of preoperative NLR in patients undergoing radical nephroureterectomy (RNU) for
      UTUC to assess its prognostic potential. MATERIALS AND METHODS: A systematic
      search of Web of Science, Medline/PubMed and Cochrane library was performed on
      the 1st of October, 2017. Studies were deemed eligible if they compared patients
      with high NLR before surgical treatment for UTUC to patients with low NLR to
      determine its predictive value for survival using multivariable logistic
      regression analysis. We performed a formal meta-analysis for cancer-specific
      survival (CSS), recurrence-free survival (RFS) and overall survival (OS).
      RESULTS: Nine studies including a total of 4385 patients assessing the importance
      of NLR were included in this meta-analysis. The cut-off NLR varied in the
      eligible studies ranging from 2 to 3. Increased pretreatment NLR predicted OS
      (pooled HR 1.64 95% CI; 1.23-2.17), RFS (pooled HR 1.60 95% CI; 1.16-2.20) and
      CSS (pooled HR 1.73 95% CI; 1.23-2.44) in multivariable analyses. CONCLUSION: In
      this meta-analysis, preoperative blood-based NLR is associated with worse
      prognosis in patients who underwent RNU for UTUC. NLR could be used to improve
      clinical decision making regarding RNU vs. kidney-sparing surgery, extent of
      lymphadenectomy, perioperative systemic therapy and follow-up schedule.

PMID- 29468285
TI  - Thirty years of great ape gestures.
AB  - We and our colleagues have been doing studies of great ape gestural communication
      for more than 30 years. Here we attempt to spell out what we have learned. Some
      aspects of the process have been reliably established by multiple researchers,
      for example, its intentional structure and its sensitivity to the attentional
      state of the recipient. Other aspects are more controversial. We argue here that
      it is a mistake to assimilate great ape gestures to the species-typical displays
      of other mammals by claiming that they are fixed action patterns, as there are
      many differences, including the use of attention-getters. It is also a mistake,
      we argue, to assimilate great ape gestures to human gestures by claiming that
      they are used referentially and declaratively in a human-like manner, as apes'
      "pointing" gesture has many limitations and they do not gesture iconically. Great
      ape gestures constitute a unique form of primate communication with their own
      unique qualities.

PMID- 29468286
TI  - Fibrolamellar Hepatocellular Carcinoma: Treatment with Yttrium-90 and Subsequent
      Surgical Resection.
AB  - We describe a 52-year-old female patient who presented with a 9.5-cm
      fibrolamellar hepatocellular carcinoma (FL-HCC). The patient was initially
      unsuitable for surgical resection and therefore underwent transarterial
      chemoembolization followed by selective internal radiation therapy (SIRT) with
      Yttrium-90 to downsize the tumour. Following SIRT, the tumour decreased in volume
      from 350 to 20 cm3 allowing curative (R0) resection with an extended left
      hepatectomy and reconstruction of IVC. This is the first reported case of FL-HCC
      treated with SIRT in which, due to the good SIRT response, the patient was
      downsized to allow curative resection.

PMID- 29468287
TI  - Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin.
AB  - PURPOSE: Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles can
      adsorb at the water/oil interface to stabilize the emulsion (forming Pickering
      emulsion). The purpose of this study was to compare the release profiles of
      oxaliplatin from Pickering-emulsion and Lipiodol-emulsion. MATERIALS/METHODS:
      Pickering-emulsions and Lipiodol-emulsions were both formulated with oxaliplatin
      (5 mg/mL) and Lipiodol (water/oil ratio: 1/3). For Pickering-emulsion only, PLGA
      nanoparticles (15 mg/mL) were dissolved into oxaliplatin before formulation. In
      vitro release of oxaliplatin from both emulsions was evaluated. Then, oxaliplatin
      was selectively injected into left hepatic arteries of 18 rabbits bearing VX2
      liver tumors using either 0.5 mL Pickering-emulsion (n = 10) or 0.5 mL Lipiodol
      emulsion (n = 8). In each group, half of the rabbits were killed at 1 h and half
      at 24 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood
      and resulting tissue (tumors, right, and left livers) oxaliplatin concentrations.
      RESULTS: Pickering-emulsion demonstrated a slow oxaliplatin release compared to
      Lipiodol-emulsion (1.5 +/- 0.2 vs. 12.0 +/- 6% at 1 h and 15.8 +/- 3.0 vs. 85.3
      +/- 3.3% at 24 h) during in vitro comparison studies. For animal model studies,
      the plasmatic peak (Cmax) and the area under the curve (AUC) were significantly
      lower with Pickering-emulsion compared to Lipiodol-emulsion (Cmax = 0.49 +/- 0.14
      vs. 1.08 +/- 0.41 ng/mL, p = 0.01 and AUC = 19.8 +/- 5.9 vs. 31.8 +/- 14.9, p =
      0.03). This resulted in significantly lower oxaliplatin concentrations in tissues
      at 1 h with Pickering-emulsion but higher ratio between tumor and left liver at
      24 h (43.4 vs. 14.5, p = 0.04). CONCLUSION: Slow release of oxaliplatin from
      Pickering-emulsion results in a significant decrease in systemic drug exposure
      and higher ratio between tumor and left liver oxaliplatin concentration at 24 h.

PMID- 29468288
TI  - Efficacy of Mechanical Thrombectomy Using Stent Retriever and Balloon-Guiding
      Catheter.
AB  - PURPOSE: Intra-arterial therapy of acute ischemic stroke has developed rapidly in
      recent years. Due to proven efficacy in randomized trials, stent retrievers were
      replacing first-generation thrombectomy devices and have been defined as method
      of choice. However, aspiration catheters or a combination of several techniques
      have shown promising rates of successful recanalizations. To create a basis for
      comparison of the new approaches according to real-world data, we determined the
      first pass recanalization rate of an evidence-based standard technique with the
      use of a stent retriever in combination with a balloon-guiding catheter. The
      assessment was based on the number of required passages and reperfusion rate, but
      not on clinical results. METHODS: Patients from our institution with anterior
      circulation occlusions and mechanical thrombectomy by using stent retrievers in
      combination with balloon-guiding catheters were analyzed retrospectively.
      Reperfusion was graded with the "thrombolysis in cerebral infarction" (TICI)
      classification on post-interventional angiograms. Additionally, the number of
      passes and the duration of the recanalization procedure were recorded. RESULTS:
      Between 2014 and July 2017, 201 patients met the inclusion criteria. Successful
      recanalization, defined as a TICI scale 2b/3, was 91% (TICI 2b was achieved in
      44% and TICI 3 in 47%) after the procedure. After the first passage, successful
      recanalization was achieved in 65% of the patients. Mean number of passes was 1.4
      (1-5 passes) for all patients. Median duration of the procedure was 49 min (0:11
      2:35 h). CONCLUSIONS: Even a standard thrombectomy technique with the use of a
      stent retriever together with a balloon-guiding catheter provides reasonable
      recanalization rates with only one passage. The results can be taken as benchmark
      for alternative and more complex techniques.

PMID- 29468289
TI  - Effect of Cryopreservation on Enzyme and Transporter Activities in Suspended and
      Sandwich Cultured Rat Hepatocytes.
AB  - Freshly-isolated rat hepatocytes are commonly used as tools for hepatic drug
      disposition. From an ethical point of view, it is important to maximize the use
      of isolated hepatocytes by cryopreservation. The present study compared overall
      hepatocyte functionality as well as activity of the organic anion transporting
      polypeptide (Oatp), multidrug resistance-associated protein 2 (Mrp2), and UDP
      glucuronosyltransferase 1 (Ugt1), in in vitro models established with
      cryopreserved and freshly-isolated hepatocytes. A similar culture time-dependent
      decline in cellular functionality, as assessed by urea production, was observed
      in sandwich-cultured hepatocytes (SCH) obtained from freshly-isolated and
      cryopreserved cells. Concentration-dependent uptake kinetics of the Oatp
      substrate sodium fluorescein in suspended hepatocytes (SH) or SCH were not
      significantly affected by cryopreservation. Mrp2-mediated biliary excretion of 5
      (and 6)-carboxy-2',7'-dichlorofluorescein by SCH was assessed with semi
      quantitative fluorescence imaging: biliary excretion index values increased
      between day 3 and day 4, but did not differ significantly between cryopreserved
      and freshly-isolated hepatocytes. Finally, telmisartan disposition was evaluated
      in SCH to simultaneously explore Oatp, Ugt1, and Mrp2 activity. In order to
      distinguish between the susceptibilities of the individual disposition pathways
      to cryopreservation, a mechanistic cellular disposition model was developed.
      Basolateral and canalicular efflux as well as glucuronidation of telmisartan were
      affected by cryopreservation. In contrast, the disposition parameters of
      telmisartan-glucuronide were not impacted by cryopreservation. Overall, the
      relative contribution of the rate-determining processes (uptake, metabolism,
      efflux) remained unaltered between cryopreserved and freshly-isolated
      hepatocytes, indicating that cryopreserved hepatocytes are a suitable alternative
      for freshly-isolated hepatocytes when studying these cellular disposition
      pathways.

PMID- 29468290
TI  - [Early undifferentiated arthritis].
AB  - Early recognition and treatment of inflammatory arthritis is imperative for the
      further course of the disease. Patients with inflammatory arthritis should be
      referred as early as possible to a rheumatologist for further management. A
      combination of anamnesis, clinical examination, imaging and laboratory
      measurements enable a differential diagnosis. If a specific diagnosis is not
      possible, the disease is called early undifferentiated arthritis. Early effective
      treatment should be instituted for those at risk of developing persistent and/or
      erosive arthritis. Treatment includes both pharmacological and non
      pharmacological options. In the management of early arthritis a combination of
      regular monitoring and optimal treatment interventions are paramount to achieve
      remission and improve outcome of the disease (treat-to-target).

PMID- 29468291
TI  - Lymphangiomatosis: a rare entity presenting with involvement of the sacral
      plexus.
AB  - Lymphangiomatosis is an uncommon disease process characterized by multisystem
      lymphatic malformations that can involve numerous body systems, including organs,
      muscles, soft tissues, and bones. Involvement of the nervous system is rare and
      has even been previously described as a site of sparing. We present a case of a
      24-year-old female with known lymphangiomatosis, presenting with acute onset of
      lower extremity paresthesias, weakness, and new urinary retention. MRI of the
      pelvis revealed lymphangiomatosis of the sacral plexus, which has not been
      previously reported. We will review the clinical and imaging manifestations of
      lymphangiomatosis and provide a differential diagnosis for masses of the
      lumbosacral plexus. Although lower extremity pain and weakness encountered in the
      emergency department or outpatient setting is most frequently caused by lumbar
      spine pathology, occasionally, abnormalities of the lumbosacral plexus may prove
      to be the cause. While peripheral nerve sheath tumors lead the differential
      diagnosis of tumor or tumor-like entities involving the lumbosacral plexus,
      lymphangiomatosis is a rare differential consideration.

PMID- 29468292
TI  - Compact devices for generation of reference trace VOC mixtures: a new concept in
      assuring quality at chemical and biochemical laboratories.
AB  - Volatile organic compounds (VOCs) in gas mixtures at trace level (nmol/mol) are
      routinely measured by chemical and biochemical laboratories as climate
      indicators, indoor air quality pollutants from building materials emissions,
      contaminants in food and beverages, and biomarkers in body fluids (blood, urine,
      breath) of occupational exposure or human diseases. Current analytical
      instruments used for measurements are gas chromatographs equipped with various
      injector and detector configurations. The assurance of measurement quality is
      done by using a huge amount of certified liquid VOC standard solutions (or
      gaseous VOC standard cylinders) with multiple dilutions to reach the required
      trace level. This causes high standard uncertainty in instrument calibrations,
      high cost, and high consumption of analysis and laboratory personal time. In this
      paper, we present the implementation of portable generators producing VOC gas
      standards at trace level for automatic and direct calibration of VOC detectors
      employed in various contexts, removing the need for preparation of matrix
      calibration standards in cylinders. Two compact devices in-house developed by two
      national metrology institutes-the Istituto Nazionale di Ricerca Metrologica
      (INRIM) and the Federal Institute of Metrology (METAS)-are here used to
      dynamically generate reference gas mixtures in an SI traceable way. The two
      devices are based on different technologies: diffusion and permeation, for INRIM
      and METAS, respectively. A metrological characterization is given and the
      practical implementation at chemical and biochemical laboratories is discussed.
      Graphical abstract Onsite calibration with transportable generation system with
      similar performances to primary laboratory devices.

PMID- 29468293
TI  - Salt-induced ionic liquid-based microextraction using a low cytotoxic guanidinium
      ionic liquid and liquid chromatography with fluorescence detection to determine
      monohydroxylated polycyclic aromatic hydrocarbons in urine.
AB  - A novel ionic liquid (IL)-based microextraction method has been developed for the
      determination of four hydroxylated polycyclic aromatic hydrocarbons (OHPAHs) in
      urine samples. The water soluble IL-based surfactant selected as extraction
      solvent is decylguanidinium chloride (C10Gu-Cl), the cytotoxicity and micellar
      behavior of which were evaluated. The proposed salt-induced IL-based
      preconcentration method simply consists in adding NaClO4 to the aqueous medium
      containing the IL to promote its water insolubility. The entire method was
      optimized, requiring the use of only 20 MUL of C10Gu-Cl for 10 mL of diluted
      urine sample (1:10) without any pH adjustment, followed by the addition of NaClO4
      to ensure a 5% (w/v) content. A cloudy solution was observed immediately, and
      after the application of 4 min of vortex and 8 min of centrifugation, the droplet
      was diluted up to 60 MUL with a mixture of acetonitrile:water (30:70) and
      injected into the liquid chromatograph with fluorescence detection. The method
      was validated using both synthetic urine and human urine as matrix for the
      determination of the four OHPAHs. The following analytical features were
      obtained: detection limits down to 1 ng.L-1 in real urine; inter-day
      reproducibility (as RSD in %) always lower than 17% when dealing with real urine
      samples spiked at 80 ng.L-1; and average relative recoveries of 102% in real
      urine samples at such low spiked levels. Despite the simplicity of the proposed
      method, it performed successfully with complex urine samples. Graphical abstract
      Salt-induced IL-based microextraction using a low cytotoxic IL for mono-OHPAHs in
      urine.

PMID- 29468294
TI  - Behavioral phenotyping and dopamine dynamics in mice with conditional deletion of
      the glutamate transporter GLT-1 in neurons: resistance to the acute locomotor
      effects of amphetamine.
AB  - RATIONALE: GLT-1 is the major glutamate transporter in the brain and is expressed
      predominantly in astrocytes but is also present in excitatory axon terminals. To
      understand the functional significance of GLT-1 expressed in neurons, we
      generated a conditional GLT-1 knockout mouse and inactivated GLT-1 in neurons
      using Cre-recombinase expressed under the synapsin 1 promoter, (synGLT-1 KO).
      OBJECTIVES: Abnormalities of glutamate homeostasis have been shown to affect
      hippocampal-related behaviors including learning and memory as well as responses
      to drugs of abuse. Here, we asked whether deletion of GLT-1 specifically from
      neurons would affect behaviors that assessed locomotor activity, cognitive
      function, sensorimotor gating, social interaction, as well as amphetamine
      stimulated locomotor activity. METHODS/RESULTS: We found that the neuronal GLT-1
      KO mice performed similarly to littermate controls in the behavioral tests we
      studied. Although performance in open field testing was normal, the acute
      locomotor response to amphetamine was significantly blunted in the synGLT-1 KO
      (40% of control). We found no change in amphetamine-stimulated extracellular
      dopamine in the medial shell of the nucleus accumbens, no change in electrically
      stimulated or amphetamine-induced dopamine release, and no change in dopamine
      tissue content. CONCLUSIONS: These results support the view that GLT-1 expression
      in neurons is required for amphetamine-induced behavioral activation, and suggest
      that this phenotype is not produced through a change in dopamine uptake or
      release. Although GLT-1 is highly expressed in neurons in the CA3 region of the
      hippocampus, the tests used in this study were not able to detect a behavioral
      phenotype referable to hippocampal dysfunction.

PMID- 29468295
TI  - [Conjunctival melanoma : Standard operating procedures in diagnosis, treatment
      and follow-up care].
AB  - BACKGROUND: In cases of rare cancer entities, such as malignant melanoma of the
      conjunctiva, there are often no evidence-based national guidelines available.
      Standard operating procedures (SOP) are an alternative in these cases. OBJECTIVE:
      The aim of this project was to develop a consensus SOP for diagnosis, treatment,
      and follow-up care of conjunctival melanomas between the 14 Centers of Excellence
      in Germany supported by German Cancer Aid. METHODS: The SOP was prepared
      according to a defined process including timelines, flow of information, and
      roles. RESULTS AND CONCLUSION: This is the first consensus SOP of the Centers of
      Excellence in Germany (certified by the German Cancer Aid) regarding diagnosis,
      treatment, and follow-up for malignant melanomas of the conjunctiva.

PMID- 29468296
TI  - [Corneal densitometry : Value for keratoconus diagnostics].
AB  - BACKGROUND: Corneal densitometry, based on the Scheimpflug principle, is a useful
      noninvasive tool for quantitative evaluation of the optical quality of the
      cornea. It enables us to evaluate corneal transparency in the different corneal
      layers and different annuli. In this article, we discuss the basis of application
      of corneal densitometry measurements and summarize findings in patients with
      keratoconus. METHODS: This article is based on a selective literature review and
      analysis of own data. RESULTS: Patients with keratoconus have significant higher
      corneal densitometry values compared to healthy controls. Densitometry values
      also correlate with the extent of the disease. In the first months after corneal
      cross-linking (CXL), haze formation occurs and leads to a decrease in corneal
      transparency, thus densitometry peaks. Long-term analysis of densitometric data
      have shown that corneal transparency then starts to decrease after 3 to 6 months,
      and improves further with time. At 24 to 36 months after CXL, corneal
      transparency levels might achieve physiological values. CONCLUSION: Corneal
      transparency is reduced in patients with keratoconus. In the first months after
      CXL, haze formation and a reduction in corneal transparency can be observed,
      which subsequently improve with time.

PMID- 29468297
TI  - Aldopentoses as new substrates for the membrane-bound, pyrroloquinoline quinone
      dependent glycerol (polyol) dehydrogenase of Gluconobacter sp.
AB  - Membrane-bound, pyrroloquinoline quinone (PQQ)-dependent glycerol dehydrogenase
      (GLDH, or polyol dehydrogenase) of Gluconobacter sp. oxidizes various secondary
      alcohols to produce the corresponding ketones, such as oxidation of D-sorbitol to
      L-sorbose in vitamin C production. Substrate specificity of GLDH is considered
      limited to secondary alcohols in the D-erythro configuration at the next to the
      last carbon. Here, we suggest that L-ribose, D- and L-lyxoses, and L-tagatose are
      also substrates of GLDH, but these sugars do not meet the substrate specificity
      rule of GLDH. The oxygen consumption activity of wild-type Gluconobacter
      frateurii cell membranes depends on several kinds of sugars as compared with that
      of the membranes of a GLDH-negative variant. Biotransformation of those sugars
      with the membranes was examined to determine the reaction products. A time course
      measuring the pH in the reaction mixture and the increase or decrease in
      substrates and products on TLC suggested that oxidation products of L-lyxose and
      L-tagatose were ketones with unknown structures, but those of L-ribose and D
      lyxose were acids. The oxidation product of L-ribose was purified and revealed to
      be L-ribonate by HRMS and NMR analysis. Biotransformation of L-ribose with the
      membranes and also with the whole cells produced L-ribonate in nearly
      stoichiometric amounts, indicating that the specific oxidation site in L-ribose
      is recognized by GLDH. Since purified GLDH produced L-ribonate without any
      intermediate-like compounds, we propose here a reaction model where the first
      carbon in the pyranose form of L-ribose is oxidized by GLDH to L-ribonolactone,
      which is further hydrolyzed spontaneously to produce L-ribonate.

PMID- 29468298
TI  - Endoscopy, histology and electron microscopy analysis of foetal membranes in
      pregnant South American plains vizcacha reveal unusual excrescences on the yolk
      sac.
AB  - The South American hystricognathe Lagostomus maximus is a fossorial rodent whose
      females show unique reproductive characteristics. They have a 155-day long
      gestation, show massive polyovulation and a selective process of embryonic
      resorption in the first half of gestation. In order to explore and perform an in
      situ characterization of the reproductive tract, we visualized internal
      structures through ultrasonography and video-endoscopy in pregnant and non
      pregnant females. We describe the finding of protruding structures that lie on
      the yolk sac and their histological and ultrastructural characterization. The
      placenta was covered with whitish, small pearl-shaped structures. These
      structures were also seen on the extra-embryonic space, being the amnion and the
      umbilical cord free of them. Pearl-shaped structures were composed with loose
      connective tissue, lacked blood vessels, and showed collagen fibers organized in
      a spiral form. They were anchored by pedicles to the villous surface of the
      extraembryonic membrane. We discuss the biological and evolutionary meaning of
      the pearl-shaped structures that relate L. maximus to the African origin of the
      South American hystricognathe fauna.

PMID- 29468299
TI  - Smad4 and epithelial-mesenchymal transition proteins in colorectal carcinoma: an
      immunohistochemical study.
AB  - Epithelial-mesenchymal transition (EMT) plays an important role in cancer
      metastasis. During EMT, tumor cells acquire the capacity to migrate and invade
      the stroma. Activation of the transforming growth factor-b (TGF-b) signaling
      pathway is of major importance for the initiation of EMT. Smad4, an essential
      protein of this pathway, is known to complex with multiple transcription factors
      (e.g. Snail-1, Slug, Twist-1), in various types of cancer, promoting the
      repression or activation of target genes. The role of Smad4 in colorectal cancer
      (CRC) is not straightforward so far. In the present study forty eight resected
      CRC tumor specimens were immunohistochemically examined in order to assess the
      expression of Smad4 and its association with E-cadherin, Snail-1, Slug, Twist-1
      protein expression and with various pathological parameters. Smad4 was found to
      be positively correlated with Snail-1, Slug and Twist-1 expression (p < 0.001).
      On the other hand it was negatively correlated with the expression of E-cadherin
      (p < 0.001). Furthermore, lymphatic invasion could be clearly associated with
      Smad4 expression, a finding complying with the metastatic ability of EMT cells.
      In conclusion, Smad4 could be considered as a central component of EMT transition
      in human colorectal cancer that combines with transcriptional factors to reduce E
      cadherin and alter the expression of the epithelial phenotype.

PMID- 29468300
TI  - Chromosomes selectively detach at one pole and quickly move towards the opposite
      pole when kinetochore microtubules are depolymerized in Mesostoma ehrenbergii
      spermatocytes.
AB  - In a typical cell division, chromosomes align at the metaphase plate before
      anaphase commences. This is not the case in Mesostoma spermatocytes. Throughout
      prometaphase, the three bivalents persistently oscillate towards and away from
      either pole, at average speeds of 5-6 MUm/min, without ever aligning at a
      metaphase plate. In our experiments, nocodazole (NOC) was added to prometaphase
      spermatocytes to depolymerize the microtubules. Traditional theories state that
      microtubules are the producers of force in the spindle, either by tubulin
      depolymerizing at the kinetochore (PacMan) or at the pole (Flux). Accordingly, if
      microtubules are quickly depolymerized, the chromosomes should arrest at the
      metaphase plate and not move. However, in 57/59 cells, at least one chromosome
      moved to a pole after NOC treatment, and in 52 of these cells, all three
      bivalents moved to the same pole. Thus, the movements are not random to one pole
      or other. After treatment with NOC, chromosome movement followed a consistent
      pattern. Bivalents stretched out towards both poles, paused, detached at one
      pole, and then the detached kinetochores quickly moved towards the other pole,
      reaching initial speeds up to more than 200 MUm/min, much greater than anything
      previously recorded in this cell. As the NOC concentration increased, the average
      speeds increased and the microtubules disappeared faster. As the kinetochores
      approached the pole, they slowed down and eventually stopped. Similar results
      were obtained with colcemid treatment. Confocal immunofluorescence microscopy
      confirms that microtubules are not associated with moving chromosomes. Thus,
      these rapid chromosome movements may be due to non-microtubule spindle components
      such as actin-myosin or the spindle matrix.

PMID- 29468301
TI  - Rapid Detection of Escherichia coli in Water Using Sample Concentration and
      Optimized Enzymatic Hydrolysis of Chromogenic Substrates.
AB  - Methods for rapid detection of fecal indicator bacteria in water are important to
      ensure that water is safe for drinking, bathing, recreation, fishing and
      shellfish harvesting. In this study, we tested experimental conditions for
      bacterial hydrolysis of two promising enzymatic substrates, 5-Bromo-4-chloro-3
      indolyl beta-D-glucuronide (X-Gluc) and Resorufin beta-D-glucuronide (REG), and
      optimized parameters such as temperature and pH to determine conditions for rapid
      reactions. We then innovated a membrane filter-based approach to facilitate more
      rapid enzyme-based detection of Escherichia coli in water based on the
      combination of an initial concentration step and optimized test conditions. For
      this approach, a water sample (10-100 mL) is filtered through a 0.45-um pore size
      filter with a diameter of 4 or 13 mm. After filtration, a newly designed rapid
      detection broth is added containing the enzymatic inducer Methyl-beta-D
      Glucuronide sodium (MetGlu) and the substrate REG or X-Gluc. After a few (1-7)
      hours of incubation at 35  degrees C, the filter shows pink color (for REG
      containing broth) or green color (for X-Gluc containing broth) if E. coli is
      present. The study provides insights and approaches towards developing a simple,
      fast, and low-cost method to detect fecal indicator bacteria in water.

PMID- 29468302
TI  - Identification of Major Enzymes Involved in the Synthesis of Diadenosine
      Tetraphosphate and/or Adenosine Tetraphosphate in Myxococcus xanthus.
AB  - Myxococcus xanthus generates diadenosine tetraphosphates (Ap4A) and diadenosine
      pentaphosphates (Ap5A) under various stress conditions. M. xanthus lysyl-tRNA
      synthetase (LysS) efficiently synthesizes Ap4A from ATP, Ap5A from ATP and
      adenosine tetraphosphate (Ap4), and Ap4 from ATP and triphosphate. To identify
      other M. xanthus enzymes that can catalyze Ap4A and Ap4 synthesis, 15 M. xanthus
      aminoacyl-tRNA synthetases (aaRSs), four acyl-CoA synthetases (Acys), three
      acetyl-CoA synthetases (Aces), phosphoglycerate kinase (Pgk), and adenylate
      kinase (Adk) were expressed in Escherichia coli and examined for Ap4A or Ap4
      synthetase activity using ATP or ATP and triphosphate as substrates. Among the
      tested enzymes, LysS had the highest Ap4A synthetase activity. AlaRS, SerRS, and
      LeuRS1 showed high ADP synthetase activity with ATP as a substrate in the
      presence of pyrophosphatase, and also demonstrated the ability to produce Ap4
      from ATP and triphosphate in the absence of pyrophosphatase. Ap4 formation by
      AlaRS, SerRS, and LeuRS1 was approximately 4- to 13-fold higher compared with
      that of Ap4A, suggesting that these enzymes prefer triphosphate over ATP as a
      substrate in the second reaction. Some of the recombinant M. xanthus Acys and
      Aces also synthesized Ap4 from ATP and triphosphate. However, Pgk was capable of
      catalyzing the production of Ap4 from ATP and 3-phosphoglycerate in the presence
      of Mg2+ and did not require triphosphate, suggesting that this enzyme is mainly
      responsible for Ap4 synthesis in M. xanthus.

PMID- 29468303
TI  - The Extracellular Polymeric Substances of Legionella pneumophila Biofilms Contain
      Amyloid Structures.
AB  - Human infection by bacteria of the genus Legionella most often result in the
      pneumonia known as Legionnaires Disease. Legionella is found as a resident of
      adherent biofilms in man-made water systems. Disinfection efforts to prevent
      Legionella infections require a better understanding of the structures that
      promote Legionella surface attachment and biofilm colonization. Various enzymatic
      treatments, including multiple carbohydrate-targeting mixtures, failed to disrupt
      Legionella biofilms, despite the presence of carbohydrates in the biofilms as
      shown by biochemical methods and concanavalin-A lectin staining. Moreover,
      Legionella biofilms contained amyloids as detected by three microscopic staining
      methods (congo red, thioflavin T, and the amyloid-specific antibody WO2). Amyloid
      structures were seen in biofilms of both L. pneumophila and L. longbeachae, the
      two Legionella species most associated with human infection. Inhibition of
      amyloid assembly by congo red and thioflavin T limited both self-aggregation and
      surface attachment of L. pneumophila, indicating that functional amyloid
      structures have a key role in initial biofilm formation by these pathogenic
      bacteria.

PMID- 29468304
TI  - Genetic Analysis of the Listeria Pathogenicity Island 1 of Listeria monocytogenes
      1/2a and 4b Isolates.
AB  - The aim of the present study was to apply descriptive, phylogenetic,
      recombination, and selection analyses on alignments of the Listeria Pathogenicity
      Island 1 (LIPI-1) of 1/2a and 4b Listeria monocytogenes isolates of different
      origin in order to gain insights into the evolution of this virulence gene
      cluster. For that purpose, a total of 19 L. monocytogenes isolates (9 meat
      isolates, serotype 1/2a; 5 meat isolates, serotype 4b; 5 strawberry isolates,
      serotype 4b) that have been previously separated at strain level were subjected
      to sequencing of their LIPI-1. Descriptive analysis revealed extensive nucleotide
      diversity mostly in the intragenic regions. The actA gene of 1/2a and 4b meat
      isolates and the hly gene of the 4b strawberry isolates exhibited the higher
      diversity; limited diversity was observed in prfA and plcA genes of the 4b
      isolates and mpl gene of the 1/2a isolates. Phylogenetic analysis of the complete
      island resulted in two major clusters that were consistent with serotype
      assignment of the isolates. Moreover, effective discrimination between serotypes
      was obtained by plcA, plcB, mpl, actA and the intergenic regions plcA-prfA and
      plcA-hly. In all cases but plcB and plcA-prfA 4b isolates were also
      differentiated according to their source of isolation as well. Selection analysis
      revealed that the island consisted of randomly evolving DNA with the exception of
      prfA gene of 1/2a isolates and actA gene of 4b meat isolates for which purifying
      selection or population expansion was indicated. Finally, no statistically
      significant evidence for recombination has been observed.

PMID- 29468305
TI  - Transovarian Transmission of Blochmannia and Wolbachia Endosymbionts in the
      Neotropical Weaver Ant Camponotus textor (Hymenoptera, Formicidae).
AB  - Camponotus is a hyper-diverse ant genus that is associated with the obligate
      endosymbiont Blochmannia, and often also with Wolbachia, but morphological
      studies on the location of these bacteria in the queen's ovaries during oogenesis
      remain limited. In the present study, we used the Neotropical weaver ant
      Camponotus textor to characterize the ovary using histology (HE) techniques, and
      to document the location of Blochmannia and Wolbachia during oogenesis through
      fluorescence in situ hybridization (FISH). This is the first morphological report
      of these two bacteria in the same host with polytrophic meroistic ovaries and
      reveals that Blochmannia is found inside late-stage oocytes and Wolbachia is
      associated with the nuclei of the nurse cells. Our results provide insights into
      the developmental sequence of when these bacteria reach the egg, with Blochmannia
      establishing itself in the egg first, and Wolbachia only reaching the egg shortly
      before completing egg development. Studies such as this provide understanding
      about the mechanisms and timing of the establishment of these endosymbionts in
      the host.

PMID- 29468306
TI  - Paratesticular alveolar rhabdomyosarcomas do not harbor typical translocations: a
      distinct entity with favorable prognosis?
AB  - The alveolar subtype of rhabdomyosarcoma (RMA) is a strong risk factor. Cases of
      RMA located in paratesticular sites have however been reported to have similar
      outcomes to those of embryonal rhabdomyosarcoma (RME). We wanted to re-evaluate
      the impact of subtype in paratesticular rhabdomyosarcoma (PT-RMS). Patients from
      a population-based cohort diagnosed with paratesticular RMA in 1990-2013 were
      analyzed. All tumor samples were re-reviewed using conventional morphology,
      immunohistochemistry, and molecular testing. Seven patients were eligible. Four
      tumors showed focal areas morphologically compatible with RMA (mixed RMA/RME).
      One case was undifferentiated, with a solid round-cell morphology which had to be
      reclassified as poorly differentiated RME. Two cases had a "microalveolar"
      morphology which is today regarded as sclerosing RME. No tumor showed the
      characteristic gene fusion of RMA. Five children had localized disease, one bone
      metastases, and another lymph-node involvement. All primaries were grossly
      resected. One locoregional relapse occurred. At a median follow-up of 7 years,
      all patients were alive disease-free. PT-RMS can show a focal alveolar histology
      combined with typical features of RME. In current morphological classifications,
      all rhabdomyosarcomas qualify for the alveolar subtype if typical features of RMA
      are realized at least focally. Rhabdomyosarcomas consisting of pure RMA
      morphology were however not found in our patients with PT-RMS. The mixed RMA/RMEs
      identified in our population-based study did not show a translocation typical for
      RMA and had a good prognosis. Further prospective studies need to evaluate if
      mixed RMA/RMEs have a similar favorable outcome in non-paratesticular sites as
      well.

PMID- 29468307
TI  - Understanding the antimicrobial properties/activity of an 11-residue Lys
      homopeptide by alanine and proline scan.
AB  - Previous work demonstrated that lysine homopeptides adopt a polyproline II (PPII)
      structure. Lysine homopeptides with odd number of residues, especially with 11
      residues (K11), were capable of inhibiting the growth of a broader spectrum of
      bacteria than those with an even number. Confocal studies also determined that
      K11 was able to localize exclusively in the bacterial membrane, leading to cell
      death. In this work, the mechanism of action of this peptide was further analyzed
      focused on examining the structural changes in bacterial membrane induced by K11,
      and in K11 itself when interacting with bacterial membrane lipids. Moreover,
      alanine and proline scans were performed for K11 to identify relevant positions
      in structure conformation and antibacterial activity. To do so, circular
      dichroism spectroscopy (CD) was conducted in saline phosphate buffer (PBS) and in
      lipidic vesicles, using large unilamellar vesicles (LUV), composed of 2
      dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) or bacterial membrane lipid.
      Antimicrobial activity of K11 and their analogs was evaluated in Gram-positive
      and Gram-negative bacterial strains. The scanning electron microscopy (SEM)
      micrographs of Staphylococcus aureus ATCC 25923 exposed to the Lys homopeptide at
      MIC concentration showed blisters and bubbles formed on the bacterial surface,
      suggesting that K11 exerts its action by destabilizing the bacterial membrane. CD
      analysis revealed a remarkably enhanced PPII structure of K11 when replacing some
      of its central residues by proline in PBS. However, when such peptide analogs
      were confronted with either DMPG-LUV or membrane lipid extract-LUV, the tendency
      to form PPII structure was severely weakened. On the contrary, K11 peptide showed
      a remarkably enhanced PPII structure in the presence of DMPG-LUV. Antibacterial
      tests revealed that K11 was able to inhibit all tested bacteria with an MIC value
      of 5 uM, while proline and alanine analogs have a reduced activity on Listeria
      monocytogenes. Besides, the activity against Vibrio parahaemolyticus was affected
      in most of the alanine-substituted analogs. However, lysine substitutions by
      alanine or proline at position 7 did not alter the activity against all tested
      bacterial strains, suggesting that this position can be screened to find a
      substitute amino acid yielding a peptide with increased antibacterial activity.
      These results also indicate that the PPII secondary structure of K11 is
      stabilized by the interaction of the peptide with negatively charged
      phospholipids in the bacterial membrane, though not being the sole determinant
      for its antimicrobial activity.

PMID- 29468308
TI  - Cross-sectional study of contraceptive use among Chinese women of reproductive
      age: results based on a mobile application (APP)-derived data.
AB  - PURPOSE: To evaluate the contraceptive status among Chinese women of reproductive
      age and factors associated with contraceptive methods. METHODS: A cross-sectional
      study from November 2015 to January 2016 was conducted. We used APP to collect
      demographics and contraceptive use information of women aged 14-44 years in
      China. RESULTS: A total of 23,669 women completed the study. After data cleaning,
      19,768 (83.5%) women were included in the final analysis. The prevalence of
      contraceptive use was 78.9%; while 21.05% of women did not use any method,
      condoms (40.10%), rhythm, or withdrawal (31.03%) were the most commonly used
      methods. When contraceptive methods were divided into four categories-long-acting
      contraceptives (LAC), short-acting contraceptive (SAC), Others, and "No use"-the
      prevalence was 6.1% (601/19,678), 40.8% (8022/19,678), 35.1% (6912/19,678), and
      21.1% (4143/19,678), respectively. Women with a high level of education, being
      unmarried, and sexually active women tended to choose SAC; married women were
      associated with LAC usage. Women with irregular menstrual cycle used a high
      proportion of emergency contraception. CONCLUSIONS: The prevalence of
      contraceptive use was 78.9%, with condom use being most prominent. Young women of
      reproductive age have low awareness of contraception. Relevant departments should
      take necessary measures to improve this situation.

PMID- 29468309
TI  - Factors associated with late fetal mortality.
AB  - PURPOSE: Perinatal mortality has been decreasing in Europe thanks to a reduction
      in neonatal mortality. The causes of fetal mortality remain poorly studied. The
      objective was to determine the late fetal mortality rate in Spain in 2015 and the
      associated factors. METHODS: A cross-sectional study was performed using data
      regarding births in 2015 in Spain extracted from the National Institute of
      Statistics. Single births at 28 or more weeks of pregnancy were included. The
      sample comprised 340,371 births. Sociodemographic, obstetrical and neonatal
      variables were analyzed using univariate and multivariate logistic regression
      (MLR), with the fetal mortality from 28 weeks of pregnancy as the dependent
      variable. RESULTS: The total number of late fetal deaths was 884 (2.6 * 1000).
      The MLR model showed that the following factors were associated with late fetal
      mortality: birth before 37 weeks of pregnancy (OR 13.1); weight of the newborn <
      2500 g (OR 3.22) and >= 4000 g (OR 3.36); low training level (OR 2.28); and
      others, such as African origin, maternal age >= 35 years, primiparity and mothers
      who were single. CONCLUSIONS: The rate of late fetal mortality in Spain has not
      decreased and has remained at the same level as in 2010. This result is related
      to prematurity, low birth weight, macrosomia and sociodemographic factors, such
      as low maternal preparation, mothers of African origin, age >= 35 years and
      mothers who are single. It is necessary to improve the quality and accessibility
      of prenatal care and the early detection of risk factors.

PMID- 29468310
TI  - Cancer metastasizes to the bone marrow and not to the bone: time for a paradigm
      shift!

PMID- 29468311
TI  - 68Ga-PSMA-PET/CT imaging of localized primary prostate cancer patients for
      intensity modulated radiation therapy treatment planning with integrated boost.
AB  - PURPOSE: The purpose of our study was to show the feasibility and potential
      benefits of using 68Ga-PSMA-PET/CT imaging for radiation therapy treatment
      planning of patients with primary prostate cancer using either integrated boost
      on the PET-positive volume or localized treatment of the PET-positive volume. The
      potential gain of such an approach, the improvement of tumor control, and
      reduction of the dose to organs-at-risk at the same time was analyzed using the
      QUANTEC biological model. METHODS: Twenty-one prostate cancer patients (70 years
      average) without previous local therapy received 68Ga-PSMA-PET/CT imaging. Organs
      at-risk and standard prostate target volumes were manually defined on the
      obtained datasets. A PET active volume (PTV_PET) was segmented with a 40% of the
      maximum activity uptake in the lesion as threshold followed by manual adaption.
      Five different treatment plan variations were calculated for each patient.
      Analysis of derived treatment plans was done according to QUANTEC with in-house
      developed software. Tumor control probability (TCP) and normal tissue
      complication probability (NTCP) was calculated for all plan variations. RESULTS:
      Comparing the conventional plans to the plans with integrated boost and plans
      just treating the PET-positive tumor volume, we found that TCP increased to (95.2
      +/- 0.5%) for an integrated boost with 75.6 Gy, (98.1 +/- 0.3%) for an integrated
      boost with 80 Gy, (94.7 +/- 0.8%) for treatment of PET-positive volume with 75
      Gy, and to (99.4 +/- 0.1%) for treating PET-positive volume with 95 Gy (all p <
      0.0001). For the integrated boost with 80 Gy, a significant increase of the
      median NTCP of the rectum was found, for all other plans no statistical
      significant increase in the NTCP neither of the rectum nor the bladder was found.
      CONCLUSIONS: Our study demonstrates that the use of 68Ga-PSMA-PET/CT image
      information allows for more individualized prostate treatment planning. TCP
      values of identified active tumor volumes were increased, while rectum and
      bladder NTCP values either remained the same or were even lower. However, further
      studies need to clarify the clinical benefit for the patients applying these
      techniques.

PMID- 29468312
TI  - Evaluation on the reliability of the permeability coefficient (Kp) to assess the
      percutaneous penetration property of chemicals on the basis of Flynn's dataset.
AB  - PURPOSE: The permeability coefficient (Kp) is often used for prediction of the
      dermal penetration of chemicals. Mathematical models have mostly been derived on
      Kp data basis. However, confusing Kp values are reported, questioning the general
      reliability of this parameter. In this study, we tested the plausibility of Kp
      values expressing the dermal penetration velocity (cm h-1) of chemicals on a
      larger dataset from literature. METHODS: Kp was applied for the calculation of
      the time for penetration through skin membranes of defined thickness
      (tCrossSkin). Kp values were obtained from Flynn's dataset (1990), containing
      data determined mostly under similar experimental conditions using diffusion
      cells. Further skin penetration parameters, e.g., times at which the chemicals
      were firstly measured in the receptor phase, lag times, steady-state times, and
      exposure duration, where available, were related to Kp values. The data
      congruence was tested comparing Kp values from Flynn's dataset with those
      reported in the EDETOX database. Variables, which could bias the results, such as
      different experimental protocols and research groups were also considered.
      RESULTS: Kp data for 94 chemicals matched the inclusion criteria were evaluated.
      According to the Kp values, 21 (22%) compounds would require longer than 100 h,
      and 20 (21%) further compounds longer than 10 h of exposure to penetrate skin
      membranes of ~ 0.01-2.5 mm thickness. Obviously, erroneous Kp were found in
      studies of almost all research groups in Flynn's database, indicating that
      neither the observer nor the experimental conditions alone biased the values.
      CONCLUSIONS: Our evaluation demonstrates high implausibility of Kp values to
      represent the dermal penetration velocity and supports general invalidity of the
      parameter for implementation in studies using skin membranes. The Kp should not
      be used to characterize the percutaneous penetration of chemicals or in risk
      assessment without verification.

PMID- 29468313
TI  - Correction to: Tram system related cycling injuries.
AB  - The author would like to correct the errors in the publication of the original
      article. The corrected details are given below for your reading.

PMID- 29468314
TI  - Recent Advances and Trends in Pediatric Cardiac Imaging.
AB  - Cardiac imaging is central to today's pediatric cardiology practice not only to
      diagnose structural congenital defects and delineate cardiac and extracardiac
      anatomy but also for determining the hemodynamic impact of the structural defects
      and acquired pediatric diseases. Not so long ago, clinicians had to heavily rely
      on angiography as the main cardiac imaging modality to visualize the heart.
      Particularly, the development of echocardiography in the 1970s and 1980s together
      with the development of magnetic resonance imaging (MRI) and computed tomography
      (CT) resulted in a non-invasive diagnostic revolution with diagnostic
      catheterization becoming obsolete apart for very specific indications. The
      continuous improvements in non-invasive imaging modalities allow an unprecedented
      level of understanding of cardiac morphology and function. Over the last few
      years, the specific roles of the three imaging modalities and their complementary
      roles in diagnosis and treatment have become well established resulting in a
      multimodality approach to specific congenital lesions. Recently, multimodality
      guidelines were published for postoperative tetralogy of Fallot and patients with
      transposition of the great arteries (Cohen et al. J Am Soc Echocardiogr.
      2016;29(7):571-621, Valente et al. J Am Soc Echocardiogr. 2014;27(2):111-41). In
      this paper, we aim to highlight some of the most significant advances and
      highlight some emerging trends in pediatric cardiac imaging.

PMID- 29468315
TI  - Comparative study of two spinous process (SP) osteotomy techniques for posterior
      decompression surgery in lumbar spinal stenosis: SP base versus splitting
      osteotomy.
AB  - PURPOSE: To compare the postoperative clinical and radiological outcomes of the
      SP base osteotomy versus SP splitting techniques for PD for treating LSS.
      METHODS: Of 139 patients who underwent PD surgery for LSS, 97 who met the study
      criteria were enrolled in the study. Group A comprised 53 patients who underwent
      SP base osteotomy, and group B included 44 patients who underwent SP splitting
      osteotomy. The primary study endpoint was intensity of lower back pain (LBP) and
      pain radiation to the lower extremities measured with the visual analogue scale
      (VAS). Secondary endpoints included (1) clinical outcomes assessed using Oswestry
      disability index and 12-short health form questionnaire; (2) surgical outcomes;
      and (3) procedure-related complications. RESULTS: LBP was more or less greater in
      SP base osteotomy group than in SP splitting osteotomy group at postoperative 1
      week and 1 year (P = 0.04 and 0.03), but radiating pain was no significant
      difference between the groups throughout the 1-year follow-up period. One year
      after the surgery, the fusion rate at the osteotomized site was significantly
      greater in SP splitting osteotomy group (77%) than in SP base osteotomy group
      (55%) (P = 0.03). Clinical outcomes, surgical outcomes, and complications did not
      differ significantly between groups during follow-up times. CONCLUSIONS: The two
      SP osteotomy techniques offer excellent clinical and radiological outcomes at
      least for the first year after the surgery. In fusion rate at the osteotomized SP
      site, the SP splitting technique was superior to the SP base osteotomy technique.
      These slides can be retrieved under Electronic Supplementary Material.

PMID- 29468316
TI  - Delivery of Methotrexate and Characterization of Skin Treated by Fabricated PLGA
      Microneedles and Fractional Ablative Laser.
AB  - PURPOSE: This study investigated in vitro transdermal delivery of methotrexate
      through dermatomed porcine ear and cadaver human skin treated with poly (D,L
      lactide-co-glycolide) acid microneedles or fractional ablative laser. METHODS:
      PLGA microneedles were fabricated and characterized using scanning electron
      microscopy and mechanical assessment techniques. The integrity of treated skin
      was evaluated by rheometer, transepidermal water loss, and skin electrical
      resistance measurements. Successful skin microporation was demonstrated by dye
      binding, histology, pore uniformity, confocal laser microscopy, and DermaScan
      studies. In vitro permeation experiment was performed on Franz diffusion cells to
      determine drug delivery into and across the skin. RESULTS: Both physical
      treatments resulted in a considerable decrease in skin resistance and an increase
      in transepidermal water loss value. The laser-created microchannels were
      significantly larger than those formed by microneedles (p < 0.05). An effective
      force of 41.04 +/- 18.33 N was required to achieve 100% penetration efficiency of
      the microneedles. For both porcine ear and human skin, laser ablation provided a
      significantly higher methotrexate permeability into the receptor chamber and skin
      layers compared to microneedle poration and untreated skin (p < 0.05).
      CONCLUSIONS: Both fractional ablative laser and polymeric microneedles markedly
      enhanced in vitro transdermal delivery of methotrexate into and across skin.
      Graphical Abstract ?.

PMID- 29468317
TI  - Paucibacter aquatile sp. nov. isolated from freshwater of the Nakdong River,
      Republic of Korea.
AB  - A Gram-negative, aerobic, motile, and rod-shaped bacterial strain designated
      CR182T was isolated from freshwater of the Nakdong River, Republic of Korea.
      Optimal growth conditions for this novel strain were found to be: 25-30  degrees
      C, pH 6.5-8.5, and 3% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene
      sequence indicates that the strain CR182T belongs to type strains of genus
      Paucibacter. Strain CR182T showed 98.0% 16S rRNA gene sequence similarity with
      Paucibacter oligotrophus CHU3T and formed a robust phylogenetic clade with this
      species. The average nucleotide identity value between strain CR182T and P.
      oligotrophus CHU3T was 78.4% and the genome-to-genome distance was 22.2% on
      average. The genomic DNA G+C content calculated from the genome sequence was 66.3
      mol%. Predominant cellular fatty acids of strain CR182T were summed feature 3
      (C16:1 omega7c and/or C16:1 omega6c) (31.2%) and C16:0 (16.0%). Its major
      respiratory quinine was ubiquinone Q-8. Its polar lipids consisted of
      diphosphatidylglycerol, phosphatidylethanolamine, and two unidentified
      phospholipids. Its genomic DNA G+C content was 66.3%. Based on data obtained from
      this polyphasic taxonomic study, strain CR182T represents a novel species
      belonging to genus Paucibacter, for which a name of P. aquatile sp. nov. is
      proposed. The type strain is CR182T (= KCCM 90284T = NBRC 113032T).

PMID- 29468318
TI  - How grazing affects soil quality of soils formed in the glaciated northeastern
      United States.
AB  - Historically, much of the New England landscape was converted to pasture for
      grazing animals and harvesting hay. Both consumer demand for local sustainably
      produced food, and the number of small farms is increasing in RI, highlighting
      the importance of characterizing the effects livestock have on the quality of
      pasture soils. To assess how livestock affect pasture on Charlton and Canton
      soils series in RI, we examined soil quality in farms raising beef cattle (Bos
      taurus), sheep (Ovis aries), and horses (Equus ferus caballus), using hayed
      pastures as a control. We sampled three pastures per livestock type and three
      control hayed pastures in May, August, and October 2012. Hay fields and pastures
      grazed by sheep had statistically significant (P < 0.001) better soil quality
      than pastures grazed by beef cattle or horses. This was driven by parameters
      including penetration resistance, bulk density, aggregate stability, and
      infiltration rate. Hayfields also showed higher soil quality measures than grazed
      pastures for organic matter content and active C. In addition, significant
      differences in nitrate and phosphate concentrations were observed among livestock
      types. Respiration and infiltration rates, pH, and ammonium concentrations, on
      the other hand, did not differ significantly among pasture types. When all soil
      quality indicators in this study were weighed equally, soil quality scores
      followed the order: hay > sheep > beef cattle > horses. The results of our study
      provide baseline data on the effect different types of livestock have on pasture
      soil quality in RI, which may be useful in making sound land use and agricultural
      management decisions.

PMID- 29468319
TI  - First-principles study of the structural, elastic and electronic properties of
      SbXI (X=S, Se, Te) crystals.
AB  - The structural, elastic, elastic anisotropy and electronic properties of
      ferroelectric SbSI and paraelectric SbSI, SbSeI and SbTeI crystals were computed
      using the local density approximation with first-principle calculations, based on
      density functional theory. The independent elastic constants of SbXI compounds
      were computed and the results reveal that they are mechanically stable. Some
      polycrystalline quantities such as bulk modulus, shear modulus, acoustic
      velocities, Young's modulus, Poisson's ratio, elastic anisotropy and elastic
      Debye temperatures of these compounds were derived from computed elastic
      constants. Energy band structures show that these compounds have an indirect band
      gap. The electronic charge distribution and partial density of states of SbXI
      compounds indicate that the Sb-X bond is typically covalent with a strong
      hybridization as well as Sb-I compounds that have strong ionic character. The
      results obtained were compared with experimentally measured values and other
      theoretical data.

PMID- 29468321
TI  - Correction to: Metabolism of L-arabinose in plants.
AB  - The article "Metabolism of L-arabinose in plants", written by "Toshihisa Kotake,
      Yukiko Yamanashi, Chiemi Imaizumi, Yoichi Tsumuraya", was originally published
      Online First without open access. After publication in volume129, issue 5, page
      781-792 the Botanical Society of Japan decided to opt for Open Choice and to make
      the article an open access publication.

PMID- 29468320
TI  - Effect of Permeation Enhancers on the Buccal Permeability of Nicotine: Ex vivo
      Transport Studies Complemented by MALDI MS Imaging.
AB  - PURPOSE: The purpose of this study was to assess the effect of several chemical
      permeation enhancers on the buccal permeability of nicotine and to image the
      spatial distribution of nicotine in buccal mucosa with and without buccal
      permeation enhancers. METHODS: The impact of sodium taurodeoxycholate (STDC),
      sodium dodecyl sulphate (SDS), dimethyl sulfoxide (DMSO) and Azone(r) on the
      permeability of [3H]-nicotine and [14C]-mannitol (a paracellular marker) across
      porcine buccal mucosa was studied ex vivo in modified Ussing chambers. The
      distribution of nicotine, mannitol and permeation enhancers was imaged using
      using matrix-assisted laser desorption ionization mass spectrometry imaging
      (MALDI MSI). RESULTS: Despite STDC significantly increasing permeability of [14C]
      mannitol, no enhancing effect was seen on [3H]-nicotine permeability with any of
      the permeation enhancers. Rather, SDS and DMSO retarded nicotine permeability,
      likely due to nicotine being retained in the donor compartment. The permeability
      results were complemented by the spatial distribution of nicotine and mannitol
      determined with MALDI MSI. CONCLUSIONS: The buccal permeability of nicotine was
      affected in an enhancer specific manner, suggesting that nicotine primarily
      diffuses via the transcellular pathway. MALDI MSI was shown to complement ex vivo
      permeability studies and to be a useful qualitative tool for visualizing drug and
      penetration enhancer distribution in buccal mucosa.

PMID- 29468322
TI  - Correction to: Plant actin depolymerizing factor: actin microfilament disassembly
      and more.
AB  - The article "Plant actin depolymerizing factor: actin microfilament disassembly
      and more", written by "Noriko Inada", was originally published Online First
      without open access. After publication in volume 130, issue 2, page 227-238 the
      Botanical Society of Japan decided to opt for Open Choice and to make the article
      an open access publication. Therefore, the copyright of the article has been
      changed to

PMID- 29468323
TI  - Correction to: Circadian clock during plant development.
AB  - The article" Circadian clock during plant development".

PMID- 29468324
TI  - Correction to: Importance of the green color, absorption gradient, and spectral
      absorption of chloroplasts for the radiative energy balance of leaves.
AB  - The article "Importance of the green color, absorption gradient, and spectral
      absorption of chloroplasts for the radiative energy balance of leaves", written
      by Atsushi Kume, was originally published Online First without open access.

PMID- 29468325
TI  - Correction to: Role of membrane glycerolipids in photosynthesis, thylakoid
      biogenesis and chloroplast development.
AB  - The article "Role of membrane glycerolipids in photosynthesis, thylakoid
      biogenesis and chloroplast development", written by "Koichi Kobayashi", was
      originally published Online First without open access. After publication in
      volume 129, issue 4, page 565-580 the Botanical Society of Japan decided to opt
      for Open Choice and to make the article an open access publication. Therefore,
      the copyright of the article has been changed to

PMID- 29468326
TI  - Skewed male reproductive success and pollen transfer in a small fragmented
      population of the heterodichogamous tree Machilus thunbergii.
AB  - Heterodichogamy is defined as the presence of two flower morphs that exhibit the
      male and female functions at different times among individuals within a
      population. Heterodichogamy is regarded as an adaptation to promote outcrossing
      through enhanced inter-morph mating, together with a 1:1 morph ratio. However, in
      highly fragmented populations, the morph ratio may be more likely to be biased by
      stochastic events. In such a situation, individuals of a minority morph within a
      population are expected to have higher reproductive success than those of a
      majority morph, which may suffer from pollen shortages of the minority morph. In
      this paper, we evaluated mating patterns and male reproductive success in a
      highly fragmented population of Machilus thunbergii, a putative heterodichogamous
      evergreen laurel tree. Results of paternity analysis indicated that the selfing
      rate was not clearly different between the two morphs. In contrast, the
      proportion of intra-morph mating was higher in the majority-morph (MM) mother
      trees than in the minority-morph (MF) mother trees. Bayesian estimated male
      reproductive success indicated that male reproductive success was higher in
      minority-morph (MF) than in majority-morph (MM) mother trees. These findings
      indicate that (1) the majority morph mothers, suffering a shortage of the
      opposite morph pollen, could partly compensate for the reduced reproductive
      success by intra-morph mating rather than by selfing, and (2) negative-frequency
      dependent selection may be involved in the maintenance of the two morphs.

PMID- 29468327
TI  - [Video-assisted thoracic surgery : A global development].
AB  - More than 200 years ago the first attempts at thoracoscopy were made but only
      after its introduction 25 years ago has video-assisted thoracoscopic surgery
      (VATS) experienced rapid progress. Due to worldwide cooperation and international
      networking tremendous progress of the technique was made by thoracic surgeons on
      all continents developing the technique into a less invasive operating procedure
      on the thorax. For patients this meant improvement in the quality of life and
      ultimately better survival rates following lung cancer surgery. The VATS
      procedures are nowadays the preferred method unless the size and extent of the
      tumor prohibits a minimally invasive procedure. New trends in VATS are
      ambulatory, drainless or uniportal VATS, the latter being possible because
      insufflation of carbon dioxide is not necessary, allowing manipulation with
      multiple instruments through one small incision. The other trend is robotic
      assisted thoracic surgery. The benefits of the robotics are higher degrees of
      freedom for movement of the instruments. The development of VATS is nowadays a
      global one with North America and Asian countries being the most active
      protagonists, but European countries also play an important role in shaping the
      future of minimally invasive surgery. Modern media help to further promote the
      technique.

PMID- 29468328
TI  - [Metastasized intestinal neuroendocrine tumors: Surgery for ileus prophylaxis].

PMID- 29468329
TI  - On the "bubble" of burnout's prevalence estimates : Discussion on: Psychological
      burnout and critical care medicine: big threat, big opportunity.

PMID- 29468330
TI  - Potential confounders affecting the reintubation rate : Discussion on
      "Reconnection to mechanical ventilation for 1 h after a successful spontaneous
      breathing trial reduces reintubation in critically ill patients: a multicenter
      randomized controlled trial".

PMID- 29468331
TI  - Pubovesical sling for residual incontinence after successful vesicovaginal
      fistula closure: a new approach to an old procedure.
AB  - INTRODUCTION AND HYPOTHESIS: For decades, the pubovesical (PV) sling has been in
      the armamentarium of the fistula surgeon for treating persistent urinary
      incontinence after successful fistula closure. We report our early experience
      with slings, and then also introduce a new "tight" PV sling technique for
      management of post-fistula urethral leak. Our hypothesis is that performance of
      tight slings might result in improved continence for women with persistent
      urinary incontinence after obstetric fistula closure. METHODS: Data from 120
      patients in whom some type of sling procedure had been performed between 1996 and
      2012 were extracted and labeled as "early slings." Beginning in October 2014,
      more complete data were recorded and a more uniform approach was undertaken in 40
      patients. Data were extracted from their charts and recorded as "tight slings."
      This information was analyzed using Chi-squared analysis. RESULTS: Tight slings
      were more successful in patients who had less severe fibrosis and who had a
      shorter time since initial injury. Thirty percent of women who underwent tight
      slings had improved continence at follow-up. CONCLUSION: Persistent urinary
      incontinence despite successful surgical closure of obstetrical fistula remains a
      difficult problem. Tight slings may be warranted in an attempt to avoid urinary
      diversion.

PMID- 29468332
TI  - Evaluation of tongue volume and oral cavity capacity using cone-beam computed
      tomography.
AB  - The aims of this study were to reveal the usefulness of a newly developed method
      for measuring tongue volume (TV) and oral cavity capacity (OCC) and to assess the
      relationship between them. The tongue was coated with a contrast agent, and the
      TV and OCC were determined using cone-beam computed tomography (CBCT). We
      enrolled 20 adults who were scheduled to undergo CBCT to evaluate the
      relationship of the third molar roots to the alveolar nerve before molar
      extraction. Each participant's tongue was coated with a contrast agent, and CBCT
      of the tongue and oral cavity was performed. Using computer software, we
      evaluated reconstructed 3D images of the TV, oral cavity proper volume (OCPV),
      and OCC. The mean TV was 47.07 +/- 7.08 cm3. The mean OCPV and OCC were 4.40 +/-
      2.78 cm3 and 51.47 +/- 6.46 cm3, respectively. There was a significant
      correlation between TV and OCC (r = 0.920; p < 0.01) but not between TV and OCPV.
      The mean TV/OCC ratio was 91 +/- 5%. The proposed method produced CBCT images
      that enabled effective measurement of TV and OCC. This simple method of measuring
      TV and OCC will be useful in the diagnosis on the tongues with abnormal size.

PMID- 29468333
TI  - Synthesis of multifunctional activated carbon nanocomposite comprising
      biocompatible flake nano hydroxyapatite and natural turmeric extract for the
      removal of bacteria and lead ions from aqueous solution.
AB  - Clean water, which is free from pathogens and toxic chemicals, is vital to human
      health. The blue planet is encountering remarkable challenges in meeting the ever
      increasing demands of clean water. The intention of this research study was to
      develop a water filter material that is capable of removing bacterial
      contaminants and heavy metals from fresh water using cost effective and easily
      fabricated biocompatible filter material. For this purpose, granular activated
      carbon (GAC) was coated with both hydroxyapatite (HAP) nanoflakes and turmeric
      extract (TE) (HAP/TE/GAC) which had been extracted from natural turmeric powder.
      In addition, GAC was coated only with HAP nanoflakes to synthesize HAP coated GAC
      (HAP/GAC) composite. Prepared HAP/GAC and HAP/TE/GAC were characterized using
      Fourier-transform infrared spectroscopy, X-ray diffractometry, scanning electron
      microscopy and UV-visible spectrophotometry. Antibacterial effect of the prepared
      nanocomposites, HAP/GAC and HAP/TE/GAC was compared with neat GAC using Gram
      negative bacteria Escherichia coli. Results showed that antibacterial studies of
      the synthesized nanocomposites exhibit effective antibacterial activity against
      E. coli compared with neat GAC alone. However, the composite HAP/TE/GAC revealed
      better activity than HAP/GAC. Heavy metal adsorption ability of the synthesized
      composites was carried out using Pb2+ ions at room temperature at different time
      intervals and different pH levels. The equilibrium adsorption data were assessed
      via Langmuir and Freundlich adsorption isotherm models for neat GAC, HAP/GAC and
      HAP/TE/GAC at pH 6. The equilibrium adsorption data for GAC, HAP/GAC and
      HAP/TE/GAC were well fitted with both Freundlich and Langmuir isotherm models in
      the given Pb2+ concentrations. The HAP/TE/GAC composite is capable of maintaining
      the natural function of GAC in addition to removal of bacterial contaminants and
      heavy metals, which can be used as a point-of-use water filter material.

PMID- 29468334
TI  - Characterizing the phosphorus forms extracted from soil by the Mehlich III soil
      test.
AB  - Phosphorus (P) can limit crop production in many soils, and soil testing is used
      to guide fertilizer recommendations. The Mehlich III (M3) soil test is widely
      used in North America, followed by colorimetric analysis for P, or by inductively
      coupled plasma-based spectrometry (ICP) for P and cations. However, differences
      have been observed in M3 P concentrations measured by these methods. Using 31P
      nuclear magnetic resonance (P-NMR) and mass spectrometry (MS), we characterized P
      forms in M3 extracts. In addition to the orthophosphate that would be detected
      during colorimetric analysis, several organic P forms were present in M3 extracts
      that would be unreactive colorimetrically but measured by ICP (molybdate
      unreactive P, MUP). Extraction of these P forms by M3 was confirmed by P-NMR and
      MS in NaOH-ethylenediaminetetraacetic acid extracts of whole soils and residues
      after M3 extraction. The most abundant P form in M3 extracts was myo-inositol
      hexaphosphate (myo-IHP, phytate), a compound that may not contribute to plant
      available P if tightly sorbed in soil. Concentrations of myo-IHP and other
      organic P forms varied among soils, and even among treatment plots on the same
      soil. Extraction of myo-IHP in M3 appeared to be linked to cations, with
      substantially more myo-IHP extracted from soils fertilized with alum-treated
      poultry litter than untreated litter. These results suggest that ICP analysis may
      substantially over-estimate plant-available P in samples with high MUP
      concentrations, but there is no way at present to determine MUP concentrations
      without analysis by both colorimetry and ICP. This study also tested procedures
      that will improve future soil P-NMR studies, such as treatment of acid extracts,
      and demonstrated that techniques such as P-NMR and MS are complimentary, each
      yielding additional information that analysis by a single technique may not
      provide.

PMID- 29468335
TI  - Use of speckle-tracking strain in preload-dependent patients, need for cautious
      interpretation!
AB  - BACKGROUND: In critical patients, left ventricular ejection fraction and
      fractional shortening are used to reflect left ventricular systolic function. An
      emerging technique, two-dimensional-strain echocardiography, allows assessment of
      the left ventricle systolic longitudinal deformation (global longitudinal strain)
      and the speed at which this deformation occurs (systolic strain rate). This
      technique is of increasing use in critical patients in intensive care units and
      in the peri-operative period where preload constantly varies. Our objective, in
      this prospective single-center observational study, was to evaluate the effect of
      fluid resuscitation on two-dimensional-strain echocardiography measurements in
      preload-dependent critically ill patients. We included 49 patients with preload
      dependence attested by an increase of at least 10% in the left ventricular
      outflow track velocity-time integral measured by echocardiography during a
      passive leg raising maneuver. Echocardiography was performed before fluid
      resuscitation (echocardiography 1) and after preload independency achievement
      (echocardiography 2). RESULTS: Two-dimensional-strain echocardiography was
      feasible in 40 (82%) among the 49 patients. With preload dependence correction,
      the absolute value of global longitudinal strain and systolic strain rate was
      significantly increased from, respectively, - 13.3 +/- 3.5 to - 18.4% +/- 4.5 (p
      < 0.01) and - 1.11 s-1 +/- 0.29 to - 1.55 s-1 +/- 0.55 (p < 0.001). The fluid
      resuscitation affects GLS and SSR in preload-dependent patients, with a shift,
      for GLS, from pathological to normal values. CONCLUSION: In critically ill
      patients, the assessment of the systolic function by two-dimensional-strain
      echocardiography needs prior evaluation of preload dependency, in order to
      adequately interpret this variable. Future studies should assess the ability of
      global longitudinal strain to guide fluid management in the critically ill
      patients.

PMID- 29468337
TI  - Psychosocial Impact of a Positive Gene Result for Asymptomatic Relatives at Risk
      of Hypertrophic Cardiomyopathy.
AB  - Families with a history of hypertrophic cardiomyopathy (HCM) may be offered
      genetic testing in addition to clinical surveillance. Asymptomatic family members
      who are gene positive (silent gene carriers) represent a new group of "patients"
      who may not develop HCM, with little evidence available to assist clinical
      management. This study explored experiences of HCM genetic testing to identify
      potential benefits and harms. Thirty-two individuals previously offered genetic
      testing for HCM were recruited. Semi-structured interviews were conducted face-to
      face or by phone, and transcribed audio-recordings were coded using framework
      analysis. Key themes were as follows: (1) helping the next generation, (2)
      misunderstanding risk, (3) discrepancy between actual/perceived impact.
      Participants described multiple psychological (shock, worry, uncertainty) and
      behavioural (career, sport, insurance, family planning) consequences, depending
      on perceived risk. Most considered only the benefits of genetic testing for
      children or grandchildren, but there were some cases of significant adverse
      impact. The interpretation of the HCM genetic test result is variable for silent
      gene carriers and can lead to psychological and behavioural changes. The impact
      of a positive gene result may be mitigated by increased clarity of the clinical
      consequences and efforts to ensure informed decision-making, highlighting even
      further the important role of cardiac genetic counselling.

PMID- 29468336
TI  - Parenting a Child with Phenylketonuria (PKU): an Interpretative Phenomenological
      Analysis (IPA) of the Experience of Parents.
AB  - Phenylketonuria (PKU) is a rare inherited metabolic disorder which can cause
      neurological damage if left untreated. PKU is identified through newborn
      screening in developed countries, and treatment begins immediately to prevent
      these severe consequences. When a child is diagnosed, parents must assume
      immediate responsibility for the management of PKU and prevention of neurological
      damage. Quantitative studies have identified significant psychosocial stressors
      for parents, but little is known about how the parents experience this process.
      This study aimed to explore the experiences of parents of children with PKU under
      the age of two. It is the first study to examine these experiences in this way.
      Seven parents were interviewed about their experiences, and interpretative
      phenomenological analysis was used to analyse the data. Three main themes were
      identified: control, striving for normality and acceptance of PKU as a continuum.
      Links between the themes and processes underpinning the results were explored
      with relation to existing literature and theories from a clinical psychology
      perspective. The role of acceptance of PKU was central to the parent's
      experiences. Clinical implications and suggestions for further research are
      discussed.

PMID- 29468338
TI  - Vitamin D receptor FokI, TaqI, and ApaI polymorphisms and susceptibility to
      systemic lupus erythematosus: an updated meta-analysis.
AB  - This study aimed to explore whether vitamin D receptor (VDR) polymorphisms are
      associated with susceptibility to systemic lupus erythematosus (SLE). Meta
      analyses were conducted to determine the associations between the VDR FokI, TaqI,
      and ApaI polymorphisms and SLE in all subjects and each ethnic group. A total of
      12 studies were considered in the meta-analysis, which involved 1974 patients and
      2506 controls. Meta-analysis of the VDR FokI polymorphism showed no association
      between SLE and the FokI F allele in all study subjects (OR = 1.047, 95% CI =
      0.781-1.403, p = 0.758). However, the meta-analysis showed a significant
      association between SLE and the VDR FokI F allele in the Arab population (OR =
      1.721, 95% CI = 1.417-2.088, p < 0.001). Analysis using the recessive and
      dominant models and homozygote contrast showed the same pattern for the VDR FokI
      F allele in Europeans, Asians, and Arabs. This meta-analysis showed that
      polymorphisms in VDR FokI, TaqI, and ApaI are not associated with SLE
      susceptibility in overall, European and Asian populations. However, the VDR FokI
      polymorphism is associated with SLE susceptibility in the Arab population.

PMID- 29468339
TI  - Residual disease activity in rheumatoid arthritis patients treated with
      subcutaneous biologic drugs that achieved remission or low disease activity: a
      longitudinal observational study.
AB  - The aim of this study was to evaluate the residual disease activity (RDA) and
      function in rheumatoid arthritis (RA) patients treated with subcutaneous biologic
      drugs that achieved a status of remission and low disease activity (LDA)
      according to the various indices validated for RA and to explore the factors
      associated with RDA. We consecutively enrolled RA patients that started a new
      subcutaneous biologic treatment. At baseline and after 3 and 6 months of
      treatment, we assessed the rate of patients that achieved remission or LDA using
      the Disease Activity Score on 28 joints, Clinical Disease Activity Index,
      Simplified Disease Activity Index, and American College of Rheumatology/European
      League Against Rheumatism remission criteria. The presence of RDA was evaluated
      as the rate of patients with at least tender joint count > 1, swollen joint count
      > 1, pain on VAS > 10 mm, general health (VAS) > 10, patient's disease activity
      (VAS) > 10, physician disease activity (VAS) > 10, and C reactive protein > 1
      mg/dl. We also evaluated the impaired function defined as HAQ score > 0.5.
      Factors associated to RDA were also investigated. Ninety-three adult patients
      with RA were enrolled. At 6 months, RDA occurred mostly at the level of Patient's
      reported outcome items and less frequently in tender and swollen joints and acute
      phase reactants. Interestingly, about one fourth of patients in LDA and up to one
      fifth of patients in remission had residual functional impairment with an HAQ
      score greater than 0.5. RDA in RA was present even in patients with remission or
      LDA, especially for the patient's reported outcome. Impaired function was also
      present in a significantly rate of patients.

PMID- 29468340
TI  - Phrasing of the patient global assessment in the rheumatoid arthritis ACR/EULAR
      remission criteria: an analysis of 967 patients from two databases of early and
      established rheumatoid arthritis patients.
AB  - The ACR/EULAR Boolean remission criteria for rheumatoid arthritis (RA) include a
      strict cutoff for patient global assessment (PGA, value <= 1/10). Near-remission
      corresponds to remission for joint counts and C-reactive protein but with PGA >
      1. The objective was to explore whether the contribution of PGA to remission and
      near-remission varied according to the wording of the PGA and in relation to
      disease duration. In patients with early arthritis (N = 731, French ESPOIR
      cohort) or established RA (N = 236 patients from across Europe), frequency of
      remission versus near-remission was assessed according to the phrasing used for
      PGA (global health versus disease activity). In 967 patients (mean [standard
      deviation] age 49.7 [12.7] years, 76.7% women), remission was infrequent: range
      12.9-16.7% (according to wording of PGA) in early RA and 6.8-7.2% in established
      RA. Near-remission was more frequent: 13.0-16.8% in early RA and 13.1-13.6% in
      established RA. The ratio of remission to near-remission was higher in the early
      arthritis cohort (0.8-1.3 versus 0.5-0.5 in established RA). Using the disease
      activity PGA led to more remission and less near-remission than the global health
      PGA in the early arthritis cohort (12.9 vs 16.7% near-remission, respectively, p
      = 0.047) but not in established RA. The proportion of patients who can be
      classified as remission or near-remission differs in early RA compared to
      establish RA and depends upon the formulation of the PGA question. PGA referring
      to disease activity and not global health may be preferred in early disease, if
      the objective is more alignment with inflammation assessment.

PMID- 29468341
TI  - MRI-based detection of renal artery abnormalities related to renal denervation by
      catheter-based radiofrequency ablation in drug resistant hypertensive patients.
AB  - OBJECTIVES: Endovascular renal denervation (RDN) using catheter-based
      radiofrequency (RF) ablation has emerged as a potential treatment option for drug
      resistant hypertension. Its efficacy is currently under debate. We aimed to
      evaluate the capability of contrast-enhanced magnetic resonance imaging (MRI) to
      assess the effects of RDN on the renal arterial wall in patients presenting with
      drug-resistant hypertension. METHODS: Patients were included prospectively
      following institutional review board approval and written informed consent. Renal
      arteries were imaged using a two-dimensional T1-weighted TSE sequence pre- and
      post-administration of a gadolinium-based contrast agent, before (D0), 2 days
      (D2) and 6 months (M6) after RDN. Mean enhancement of the wall (mENH) and mean
      wall thickness (mWT) were compared across time using an ANOVA with repeated
      measures and post-hoc paired t-test. RESULTS: Follow-up was completed for 23
      patients (median age, 57 years; 16 men). The mENH at D2 (96.3 +/- 36.0 %) was
      significantly higher than at D0 (61.1 +/- 26.3%, p < 0.001) and M6 (66.1+/-22.7%,
      p < 0.001). Similarly, mWT was significantly higher at D2 (3.1 +/- 0.4 m) than at
      D0 (2.7 +/- 0.4mm, p < 0.001) and M6 (2.9 +/- 0. 5 mm, p = 0.002). CONCLUSIONS:
      MRI demonstrated abnormalities of the arterial wall 2 days after RDN that had
      resolved at 6 months. KEY POINTS: * Contrast-enhanced MRI provides anatomic
      evidence of renal artery RF ablation * Temperature increase related to RF
      ablation induces transient arterial wall inflammation * Morphological effects
      observed 2 days post RF ablation are not visible after 6 months.

PMID- 29468342
TI  - Unobserved heterogeneity in work absence.
AB  - Labour absenteeism may be detrimental to firms and society because of the
      economic costs, organizational problems and production cuts that it involves.
      Although involuntary absenteeism due to accident or illness that prevents workers
      from performing their work is unavoidable, avoidable voluntary absenteeism may
      also emerge due to asymmetric information given that neither employers nor
      doctors have perfect information about workers' health status. Assuming that
      there is heterogeneity in individual's behaviour and thus some workers are more
      likely to take sick leave than others due to differences in observable and
      unobservable characteristics, we specify a Finite Mixture Model to analyse sick
      leave days per year using a sample of employees from the 2014 European Health
      Survey in Spain. This specification accounts for unobserved heterogeneity in a
      discrete way assuming that there are two types of workers even though the data do
      not allow us to identify which group any individual belongs to. Our results
      reveal that, although health indicators have the greatest impact on the
      proportional change in days of absenteeism, there is heterogeneity in sick leave
      decisions and individual and job characteristics have different effect on the
      absenteeism of each group.

PMID- 29468343
TI  - Authors' reply to Gandjour: "Modeling the cost-effectiveness of infant
      vaccination with pneumococcal conjugate vaccines in Germany".

PMID- 29468344
TI  - Co-development of Problem Gambling and Depression Symptoms in Emerging Adults: A
      Parallel-Process Latent Class Growth Model.
AB  - This study examines whether there are multiple joint trajectories of depression
      and problem gambling co-development in a sample of emerging adults. Data were
      from the Manitoba Longitudinal Study of Young Adults (n = 679), which was
      collected in 4 waves across 5 years (age 18-20 at baseline). Parallel process
      latent class growth modeling was used to identified 5 joint trajectory classes:
      low decreasing gambling, low increasing depression (81%); low stable gambling,
      moderate decreasing depression (9%); low stable gambling, high decreasing
      depression (5%); low stable gambling, moderate stable depression (3%); moderate
      stable problem gambling, no depression (2%). There was no evidence of reciprocal
      growth in problem gambling and depression in any of the joint classes.
      Multinomial logistic regression analyses of baseline risk and protective factors
      found that only neuroticism, escape-avoidance coping, and perceived level of
      family social support were significant predictors of joint trajectory class
      membership. Consistent with the pathways model framework, we observed that
      individuals in the problem gambling only class were more likely using gambling as
      a stable way to cope with negative emotions. Similarly, high levels of
      neuroticism and low levels of family support were associated with increased odds
      of being in a class with moderate to high levels of depressive symptoms (but low
      gambling problems). The results suggest that interventions for problem gambling
      and/or depression need to focus on promoting more adaptive coping skills among
      more "at-risk" young adults, and such interventions should be tailored in
      relation to specific subtypes of comorbid mental illness.

PMID- 29468345
TI  - Social Explanations of Lottery Play: New Evidence Based on National Survey Data.
AB  - This study examines the social contexts of gambling and analyzes social
      motivations for playing the lottery. We test three sociological approaches
      simultaneously: network effects, consumption theory, and strain theory. The data
      used (SOEP-IS, N = 5868 individuals) has several advantages beyond being a large
      scale representative sample of the German population. With information on
      households, we can analyze social network effects while avoiding the problems of
      egocentric network data. Another benefit of the SOEP-IS is the panel structure.
      We use the panel structure to improve measurements of strain theory by using the
      decline in income over time as a measure for it. Our results suggest that the
      three theories explain different aspects of lottery play. Networks seem to have
      an influence on lottery play. Having another person in the household playing the
      lottery is positively associated with both the probability of playing (regularly)
      and expenditures on lottery tickets. Daydreams and the belief in good luck are
      positively associated with lottery play as well. Strain theory is confirmed
      insofar as we find that a decline in income is significantly related to
      expenditures but not to the probability of playing the lottery. Overall, this
      study suggests that people play the lottery depending on their social
      surroundings, their desire to participate in a world normally out of their reach,
      and the tensions they feel from the distance between their aspirations and their
      actual social position.

PMID- 29468346
TI  - Drivers of Sexual Inactivity Among Women Living with HIV and AIDS: Findings of
      the GENIH Study in Sao Paulo, Brazil.
AB  - The advances on HIV/AIDS diagnosis and treatment have enabled people living with
      HIV/AIDS (PLHA) better quality of life. However, the persistence of HIV-related
      stigma and discrimination, and the risks triggered by HIV disclosure, may be a
      barrier to the sexual exercise of PLHA. We investigated the prevalence of sexual
      inactivity and the reasons given for it among a representative sample of women of
      reproductive age living with HIV/AIDS (WLWHA) in the municipality of Sao Paulo,
      Brazil. We surveyed 918 WLWHA with probability proportional to average number of
      visits in each of the 18 referral HIV/AIDS services. Sexual inactivity was
      defined as not having had vaginal sexual intercourse in the year prior to
      research. Statistical modeling of the factors associated with sexual inactivity
      was carried out by way of bivariate and multivariate analysis. In all, 22.2% (n =
      200) of the women did not have sexual relations in the year prior to the
      interview. The majority reported a reduction in desire (64.5%) and sexual
      activity (68%). Among the women not in a relationship, the predictors of sexual
      inactivity were: being older (35-49) (ORa = 2.25); not being Catholic (ORa =
      2.91); having kept the diagnosis secret from their partner (ORa = 2.45); having
      had up to five sexual partners throughout life (ORa = 3.81). The diagnosis of HIV
      seems to have more of an effect on the desire for and frequency of sexual
      activity than on its interruption. Sexual inactivity was influenced by the stigma
      of HIV/AIDS, by age, and by moral-religious values.

PMID- 29468347
TI  - Suitability of edaphic arthropods as prey for Proctolaelaps bickleyi and
      Cosmolaelaps brevistilis (Acari: Mesostigmata: Melicharidae, Laelapidae) under
      laboratory conditions.
AB  - Soils are often complex habitats inhabited by a wide range of organisms, some
      harmful to plants and others beneficial, for example by attacking harmful
      organisms. Beneficial organisms include predatory mites, some of which have been
      commercialized for biological control of pest insects and mites. The objective of
      this work was to evaluate under laboratory condition the suitability of
      representative soil insect and mite pests, especially Aceria tulipae (Keifer), as
      prey to the soil-inhabiting predatory mites Proctolaelaps bickleyi (Bram) and
      Cosmolaelaps brevistilis (Karg). Predation, oviposition and survivorship of
      recently molted adult females of the predators were assessed in the dark in
      rearing chambers at 25 +/- 1  degrees C and 75 +/- 3% RH. Predation rate by P.
      bickleyi on A. tulipae was significantly higher than that by C. brevistilis
      (196.3 vs. 71.0 specimens/day). About 482 A. tulipae were preyed by each P.
      bickleyi at each day, when 500 A. tulipae were made available daily to the
      predator. Oviposition rate on that prey was also higher for P. bickleyi (4.2
      eggs/day). For C. brevistilis, the highest level of oviposition was on
      Caliothrips phaseoli (Hood) (1.2 eggs/day). Survivorship was always higher for C.
      brevistilis (>= 70%), given its ability to remain alive relatively long even in
      the absence of prey. High rates of survivorship of P. bickleyi were observed on
      A. tulipae, Bradysia matogrossensis (Lane) and Protorhabditis sp. Promising
      results were obtained for P. bickleyi on A. tulipae and even on other prey,
      justifying the conduction of complementary studies under field condition.

PMID- 29468348
TI  - Effects of a mulch layer on the assemblage and abundance of mesostigmatan mites
      and other arthropods in the soil of a sugarcane agro-ecosystem in Australia.
AB  - Sugarcane farmers can utilise a soil conservation technique called green cane
      trash blanketing, a form of mulching that can increase plant productivity through
      a number of channels, e.g., via altering soil physical, chemical and biological
      characteristics, and influence soil arthropod assemblages. Predatory mites
      (Mesostigmata) are important components of soil communities because they can
      control populations of other soil-dwelling pest species. Our aim was to
      characterise mulch-influenced predatory Mesostigmata community assemblages in
      sugarcane soils in Queensland, Australia. We found that application of a mulch
      layer significantly increased the abundance of Mesostigmata, and oribatid mites
      and collembolans, in soils. Furthermore, we observed that the assemblages of
      Mesostigmata in soil covered by mulch were significantly different to those in
      bare soil; and the assemblages of Mesostigmata changed over time. The assemblages
      of Mesostigmata, but not Oribatida or collembolans, were significantly different
      in soil under mulch depending on whether the mulch was freshly laid, or
      decomposing. Our results show that the use of mulch, specifically the green cane
      trash blanket, can increase overall microarthropod abundance including
      Mesostigmata. This is likely due to increased habitat complexity and changing
      resource availability.

PMID- 29468349
TI  - Prediction of Therapeutic Response to Cyclooxygenase Inhibitors in Preterm
      Infants with Patent Ductus Arteriosus.
AB  - Patent ductus arteriosus (PDA) is a morbid condition commonly seen in premature
      infants. Cyclooxygenase (COX) inhibitors, such as indomethacin and ibuprofen, are
      often used for the treatment of PDA in preterm infants, and they work by reducing
      the production of prostaglandin. However, as observed in clinical practice, not
      all PDAs in preterm infants can be closed using COX inhibitors. Some studies have
      demonstrated that gestational age, birth weight, B-type natriuretic peptide
      (BNP), and ductal diameter can predict the therapeutic responsiveness to COX
      inhibitors. This paper reviews the factors that can predict successful closure of
      the PDA in preterm infants using indomethacin or ibuprofen and presents new
      opinions and recent findings on this topic, including the predictive roles of
      intrauterine growth restriction, timing of the treatment, and the importance of
      platelet count and arterial pH. We also discuss the prospects for future studies
      to improve the individualized therapy of PDA in premature neonates.

PMID- 29468351
TI  - Large Calibre Self-Expanding Stents for Pulmonary Stenosis After the Arterial
      Switch, a Low-Risk Solution to a Low-Flow Situation.
AB  - Branch pulmonary artery stenosis is one of the most common complications late
      after the arterial switch operation. The pathophysiology of stenosis in these
      circumstances is very different to that encountered in with normally related
      great vessels. The LeCompte manoeuvre leaves the pulmonary arteries straddled and
      stretched over the aortic root which contributing significantly to the degree of
      stenosis encountered. Unilateral branch pulmonary artery stenosis rarely leads to
      significant symptoms in young patients with biventricular repairs; however,
      significant discrepancies in the split flows between right and left lung may
      place the patient in an unfavourable physiological position as they move in to
      middle age. Balloon expandable stent implantation distorts the anatomical
      arrangement of the LeCompte and is associated with negative interactions with the
      often dilated aortic root. We present three cases of the use of flexible self
      expanding stents to improve the physiological flow distributions to each lung
      whilst hopefully decreasing the risk of erosion and perforation or fistula
      formation related to the pulmonary artery. All three patients had uncomplicated
      procedures with significant improvements in vessel diameter and flow distribution
      noted on follow-up MRI scans. This is the first report of the use of self
      expanding stents in the context of branch pulmonary artery stenosis after the
      LeCompte manoeuvre. Theoretically and based on our early experience, this
      technique provides potential safety advantages over the use of more traditional
      balloon expandable stents.

PMID- 29468350
TI  - A Novel MEF2C Loss-of-Function Mutation Associated with Congenital Double Outlet
      Right Ventricle.
AB  - Congenital heart defect (CHD) represents the most prevalent birth defect, and
      accounts for substantial morbidity and mortality in humans. Aggregating evidence
      demonstrates the genetic basis for CHD. However, CHD is a heterogeneous disease,
      and the genetic determinants underlying CHD in most patients remain unknown. In
      the present study, a cohort of 186 unrelated cases with CHD and 300 unrelated
      control individuals were recruited. The coding exons and flanking introns of the
      MEF2C gene, which encodes a transcription factor crucial for proper
      cardiovascular development, were sequenced in all study participants. The
      functional effect of an identified MEF2C mutation was characterized using a dual
      luciferase reporter assay system. As a result, a novel heterozygous MEF2C
      mutation, p.R15C, was detected in an index patient with congenital double outlet
      right ventricle (DORV) as well as ventricular septal defect. Analysis of the
      proband's pedigree showed that the mutation co-segregated with CHD with complete
      penetrance. The missense mutation, which changed the evolutionarily conserved
      amino acid, was absent in 300 control individuals. Functional deciphers revealed
      that the mutant MEF2C protein had a significantly decreased transcriptional
      activity. Furthermore, the mutation significantly reduced the synergistic
      activation between MEF2C and GATA4, another transcription factor linked to CHD.
      This study firstly associates MEF2C loss-of-function mutation with DORV in
      humans, which provides novel insight into the molecular pathogenesis of CHD,
      suggesting potential implications for genetic counseling and personalized
      treatment of CHD patients.

PMID- 29468352
TI  - Local excision for ypT2 rectal cancer following preoperative chemoradiation
      therapy: it should not be justified.
AB  - PURPOSE: Among individuals who respond well to preoperative chemoradiation
      therapy (CRT) for ypT0-1, local excision (LE) could provide acceptable
      oncological outcomes. However, in ypT2 cases, the oncological safety of LE has
      not been determined. This study aimed to compare oncological outcomes between LE
      and total mesorectal excision of ypT2-stage rectal cancer after chemoradiation
      therapy and investigate the oncological safety of LE in these patients. METHODS:
      We included 351 patients who exhibited ypT2-stage rectal cancer after CRT
      followed by LE (n = 16 [5%]) or total mesorectal excision (TME) (n = 335 [95%])
      after preoperative CRT between January 2007 and December 2013. After propensity
      matching, oncological outcomes between LE group and TME group were compared.
      RESULTS: The median follow-up period was 57 months (range, 12-113 months). In the
      LE group, local recurrence occurred more frequently (18 vs. 4%; p = 0.034) but
      not distant metastases (12 vs. 11%; p = 0.690). The 5-year local recurrence-free
      (76 vs. 96%; p = 0.006), disease-free (64 vs. 84%; p = 0.075), and overall
      survival (79 vs. 93%; p = 0.045) rates of the LE group were significantly lower
      than those of the TME group. After propensity matching, 5-year local recurrence
      free survival of the LE group was significantly lower than that of the TME group
      (76 vs. 97%, p = 0.029). CONCLUSION: The high local failure rate and poor
      oncological outcomes for ypT2-stage rectal cancer patients who undergo CRT
      followed by LE cannot be justified as an indication for LE. Salvage surgery
      should be recommended in these patients.

PMID- 29468353
TI  - Is the obesity a risk factor for delayed colonic post-polypectomy bleeding?
      authors' reply.

PMID- 29468354
TI  - Outcomes and prognostic factors of multimodality treatment for locally recurrent
      rectal cancer with curative intent.
AB  - PURPOSE: Radical management of locally recurrent rectal cancer (LRRC) can lead to
      prolonged survival. This study aims to assess outcomes and identify prognostic
      factors for patients with LRRC treated using a multimodality treatment protocol.
      METHODS: An analysis of a prospectively maintained institutional database of
      consecutive patients who underwent radical surgical resection for LRRC was
      performed. Potential prognostic factors were investigated using a Cox
      proportional hazards model. RESULTS: Ninety-eight patients were included in this
      study. A multimodality approach was taken in the majority, including preoperative
      chemoradiation (78%), intraoperative radiation therapy (47%) and adjuvant
      chemotherapy (41%). Extended resection was performed where required: bone
      resection (34%) and lateral pelvic sidewall dissection (31%). The rate of R0
      resection was 66%. Estimated rates of 5-year overall survival (OS) and
      progression-free survival (PFS) were 41.8% (95% CI 32.5-53.7) and 22.5% (95% CI
      15.3-33.1). On multivariate analysis, stage III disease at initial primary
      surgery, a positive margin at initial primary surgery, synchronous or previously
      resected oligometastases, a lateral or sacral invasive-type pelvic recurrence and
      the requirement for IORT all predicted for inferior PFS (p < 0.05). Eleven
      percent of patients subsequently underwent further pelvic surgery for pelvic re
      recurrence and had an estimated 5-year OS rate of 54.5% (95% CI 29.0-100.0) from
      repeat surgery. CONCLUSIONS: Radical multimodality management of LRRC leads to
      prolonged survival in approximately 40% of patients. Those with sacral or lateral
      invasive-type recurrence or oligometastatic disease have inferior outcomes and
      further research is needed to optimise treatment for these groups.

PMID- 29468355
TI  - Incidental findings in multislice computed tomography prior to transcatheter
      aortic valve implantation: frequency, clinical relevance and outcome.
AB  - Multislice computed tomography (MSCT) has emerged as the mainstay in patients
      planned for transcatheter aortic valve implantation (TAVI). Incidental findings
      (IF) in MSCT are common. However, the exact incidence, clinical relevance and
      further consequences of IF are unclear and it is controversial whether IF
      adversely affect patients' outcome. We analyzed MSCT data of 1050 patients
      screened for TAVI between January 2011 and December 2014. Median follow-up of
      patients was 20 months. In total, 3194 IF were identified, which were classified
      into clinically non-relevant IF (2872, 90%) and clinically relevant IF (322,
      10%). In 25% of patients (258/1050) at least one clinically relevant IF was
      present. Age (80 +/- 7 vs. 80 +/- 7 years; p = 0.198) and EuroSCORE II (3.6% [2.1
      5.7] vs. 3.6% [2.1-5.9]; p = 0.874) was similar between patients with and without
      a clinically relevant IF. TAVI was performed less frequently in patients with a
      clinically relevant IF (76% vs. 85%; p < 0.001), with more patients receiving
      surgical aortic valve replacement in that group (14% vs. 11%; p = 0.042),
      possibly due to the high rate of incidental aneurysms of the ascending aorta (n =
      48). If TAVI was performed mortality did not differ (30-days: 4% vs. 3%; p =
      0.339, 1-year: 11% vs. 14%; p = 0.226) between patients with and without a
      clinically relevant IF. Our study is the largest study to analyze prevalence,
      clinical relevance and therapeutic consequences of IF during screening for TAVI.
      IF in pre-procedural MSCT are common and clinically relevant in one-quarter of
      patients. However, these findings had no impact on overall mortality.

PMID- 29468356
TI  - Reciprocal Relations Between Parenting Behaviors and Conduct Disorder Symptoms in
      Preschool Children.
AB  - Reciprocal relations between children's conduct disorder (CD) symptoms and
      parenting behaviors were examined across the preschool years. Participants were
      199 children (M = 44.26 months, SD = 3.37; 92 girls) and their 199 mothers and
      158 fathers. CD symptoms were assessed via structured interviews; parenting was
      assessed via observational and self-report measures. Fixed effects models were
      used to assess within-individual changes and traditional cross-lagged models were
      used to assess between-individual changes; comparisons by sex were also carried
      out. Increases in maternal overreactivity predicted increases in CD symptoms.
      During the later preschool years, decreases in maternal warmth predicted
      increases in CD symptoms and increases in CD symptoms predicted increases in
      paternal overreactivity. Reciprocal effects were found between girls' CD symptoms
      and paternal negative affect. Findings suggest maternal and paternal influence on
      the development of CD symptoms and suggest that CD symptoms influence fathers'
      parenting during the preschool years.

PMID- 29468357
TI  - Sensitive Fathering Buffers the Effects of Chronic Maternal Depression on Child
      Psychopathology.
AB  - Maternal depression across the first years of life carries long-term negative
      consequences for children's well-being; yet, few studies focused on fathers as
      potential source of resilience in the context of chronic maternal depression.
      Utilizing an extreme-case design, a community birth cohort of
      married/cohabitating mothers (N = 1983) with no comorbid risk was repeatedly
      tested for maternal depression across the first year and again at 6 years,
      leading to two matched cohorts; 46 mothers with chronic depression and 103 non
      depressed controls. At 6 years, mother and child underwent psychiatric diagnosis
      and mother-child and father-child interactions observed. Partners of depressed
      mothers exhibited reduced sensitivity, lower reciprocity, and higher tension
      during interactions, particularly among children with psychopathology. Maternal
      depression increased child propensity to display Axis-I disorder upon school
      entry by fourfold. Sensitive fathering reduced this risk by half. Findings
      underscore the father's resilience-promoting role in cases of maternal depression
      and emphasize the need for father-focused interventions.

PMID- 29468359
TI  - ?

PMID- 29468358
TI  - ?

PMID- 29468360
TI  - Bariatric Surgery Coverage: a Comprehensive Budget Impact Analysis from a Payer
      Perspective.
AB  - OBJECTIVE: The objective of this study was to estimate a payer's budget impact of
      bariatric surgery coverage under (1) unrestricted, (2) budget-restricted
      ($500,000/year), and (3) quantity-restricted (100/year) medical benefit plan
      scenarios versus non-coverage in general and type 2 diabetes mellitus (T2DM)
      populations over a 10-year period. METHODS: Using recently published literature
      and health technology assessment reports, the model evaluated a hypothetical
      payer population of 100,000 members under current real-world trends: BMI-defined
      obesity groups (31.3% normal/underweight, 33% overweight, 20.4% obese, 9%
      severely obese and 6.3% morbidly obese), T2DM prevalence (6.7-27.5%; 100% for the
      T2DM model), surgery type (LAGB, BPD/DS, VSG, and RYGB), and differential
      outcomes (T2DM resolution, costs, and reoperation and complications rates).
      Assuming a surgery election rate of 1.42% among eligible candidates with a 3%
      discount rate and 10% annual surgery turnover rate, the model calculated the
      incremental cost per-member-per-month (PMPM) by estimating the difference in
      total non-T2DM and T2DM-related expected costs and savings. One-way (+/- 25%)
      sensitivity analysis was performed. RESULTS: The impact of covering bariatric
      surgery under multiple scenarios for a general (or T2DM) population ranged from
      an additional $0.3 to $3.6 (T2DM: $0.3 to $10.5) PMPM in year 1. Incremental
      costs diminished over time, breaking even between years 5 and 9 (T2DM: 5-6), and
      by year 10, cost savings were estimated to be between $1.5 and $4.8 (T2DM: $1.2
      and $31.8). CONCLUSION: Providing bariatric surgery coverage may have a modest
      short-term budget impact increase but would lead to long-term net cost savings in
      a general population model. The cost savings were much more pronounced in the
      T2DM model.

PMID- 29468361
TI  - Establishment of a multiplex real-time RT-PCR assay for rapid identification of
      H6 subtype avian influenza viruses.
AB  - The H6 subtype avian influenza viruses (AIVs) possess the capacity for zoonotic
      transmission from avian species to humans. Establishment of a specific, rapid and
      sensitive method to screen H6 AIVs is necessary. Based on the conserved domain of
      the matrix and H6 AIV hemagglutinin genes, two TaqMan minor-groove-binder probes
      and multiplex real-time RT-PCR primers were designed in this study. The multiplex
      real-time RT-PCR assay developed in this study had high specificity and
      repeatability and a detection limit of 30 copies per reaction. This rapid
      diagnostic method will be useful for clinical detection and surveillance of H6
      AIVs in China.

PMID- 29468362
TI  - Development of a nanogold slot blot inhibition assay for the detection of
      antibodies against bovine herpesvirus type 1.
AB  - Bovine herpesvirus type 1 (BoHV-1) is recognized as an important pathogen causing
      respiratory, reproductive, and neurological disorders in cattle and is associated
      with economic losses to animal industry. Accurate diagnostic methods are needed
      for prevention of disease transmission. While the virus neutralization test is
      considered the gold standard method, it requires maintenance of the virus and
      cell cultures, which is time consuming and expensive. Serological techniques such
      as enzyme-linked immunosorbent assay (ELISA) are widely applied, as these are
      easy to perform and provide quick results. In the present study, a nanogold slot
      blot inhibition assay was developed for the serological diagnosis of BoHV-1 and
      compared with standard ELISA and horseradish peroxidase (HRP) slot blot assays.
      Of 42 serum samples tested by ELISA, 32 (76.2%) were positive and 10 (23.8%),
      were negative. The sensitivity and specificity of the nanogold slot blot
      inhibition assay was similar to that observed for ELISA and HRP slot blot assays,
      and a strong correlation was observed between the tests. Thus, the nanogold slot
      blot inhibition assay may serve as an efficient and rapid alternative to ELISA in
      settings, where plate-reading equipment is lacking.

PMID- 29468363
TI  - The BCR-ABL inhibitor nilotinib influences phenotype and function of monocyte
      derived human dendritic cells.
AB  - In chronic myeloid leukemia (CML), the translocation t(9;22) results in the
      fusion protein BCR-ABL (breakpoint cluster region-abelson murine leukemia), a
      tyrosine kinase mediating oncogenic signaling which is successfully targeted by
      treatment with BCR-ABL inhibitors like imatinib. However, BCR-ABL inhibitors may
      also affect antitumor immunity. For instance, it was reported that imatinib
      impairs the function of dendritic cells (DCs) that play a central role in
      initiating and sustaining T cell responses. Meanwhile, second generation BCR-ABL
      inhibitors like nilotinib, which inhibits BCR-ABL with enhanced potency have
      become standard of treatment, at least in patients with BCR-ABL kinase domain
      mutations. In this study we analyzed the influence of therapeutic concentrations
      of nilotinib on human monocyte-derived DCs and compared its effects to imatinib.
      We found that both tyrosine kinase inhibitors (TKI) comparably and significantly
      impaired differentiation of monocytes to DCs as revealed by curtated
      downregulation of CD14 and reduced upregulation of CD1a and CD83. This was only
      partially restored after withdrawal of the TKI. Moreover, both TKI significantly
      reduced activation-induced IL-12p70 and C-C motif chemokine ligand (CCL) 3
      secretion, while divergent TKI effects for CCL2 and CCL5 were observed. In
      contrast, only nilotinib significantly impaired the migratory capacity of DCs and
      their capacity to induce T-cell immune responses in MLRs. Our results indicate
      that imatinib and nilotinib may differ significantly with regard to their
      influence on antitumor immunity. Thus, for future combinatory approaches and
      particularly stop studies in CML treatment, choice of the most suitable BCR-ABL
      inhibitor requires careful consideration.

PMID- 29468364
TI  - Antitumor in situ vaccination effect of TNFalpha and IL-12 plasmid DNA
      electrotransfer in a murine melanoma model.
AB  - Gene electrotransfer (GET) is one of the most efficient non-viral gene therapy
      approaches for the localized transfer of multiple genes into tumors in vivo;
      therefore, it is especially promising for delivering different cytokines that are
      toxic if administered systemically. In this study, we used concomitant
      intratumoral GET of two cytokines: tumor necrosis factor alpha (TNFalpha), a
      potent cytotoxic cytokine to induce in situ vaccination, and interleukin 12 (IL
      12), an immunostimulatory cytokine to boost the primed local immune response into
      a systemic one. After performing GET in murine melanoma tumors, both TNFalpha and
      IL-12 mRNA levels were significantly increased, which resulted in a pronounced
      delay in tumor growth of 27 days and a prolonged survival time of mice. An
      antitumor immune response was confirmed by extensive infiltration of immune cells
      in the tumor site, and expansion of the effector immune cells in the sentinel
      lymph nodes. Furthermore, the effect of in situ vaccination was indicated by the
      presence of vitiligo localized to the treatment area and resistance of the mice
      to secondary challenge with tumor cells. Intratumoral GET of two cytokines, one
      for in situ vaccination and one for an immune boost, proved feasible and
      effective in eliciting a potent and durable antitumor response; therefore,
      further studies of this approach are warranted.

PMID- 29468365
TI  - Testicular torsion with preserved flow: key sonographic features and value-added
      approach to diagnosis.
AB  - Testicular sonography has contributed greatly to the preoperative diagnosis of
      testicular torsion in the pediatric patient and is the mainstay for evaluation of
      acute scrotal pain. Despite its high sensitivity and specificity, both false
      negative and false-positive findings occur. Presence of documented Doppler flow
      within the testis might be a dissuading factor for surgical exploration with
      resultant testicular loss in the false-negative cases. Our goal is to illustrate
      key sonographic features in the spectrum of testicular torsion with preserved
      testicular flow, and to describe how to differentiate testicular torsion from
      epididymitis in order to avoid the under-diagnosis of testicular torsion. We
      simplify the anatomy of the bell clapper testis. We also describe our sonographic
      protocol for testicular torsion and share valuable tips from our approach to
      challenging cases.

PMID- 29468366
TI  - Utility of CT classifications to predict unfavorable outcomes in children with
      acute pancreatitis.
AB  - BACKGROUND: Computed tomography (CT) is useful for the diagnosis of local
      complications in children with acute pancreatitis but its role as a prognostic
      tool remains controversial. OBJECTIVE: To establish the correlation between the
      CT Severity Index and the Revised Atlanta Classification regarding unfavorable
      outcomes such as severe acute pancreatitis and need for Pediatric Special Care
      Unit attention in children with acute pancreatitis. MATERIALS AND METHODS: We
      conducted a retrospective and concordance cohort study in which we obtained
      abdominal CT scans from 30 patients ages 0 to 18 years with acute pancreatitis.
      Two pediatric radiologists interpreted the results using the CT Severity Index
      and the Revised Atlanta Classification. The kappa coefficient was determined for
      each scale. The association among severe acute pancreatitis, need for admission
      to the Pediatric Special Care Unit and CT systems were established using chi
      square or Mann-Whitney U tests. The best CT Severity Index value to predict the
      need for admission to the Pediatric Special Care Unit was estimated through a
      receiver operating characteristic (ROC) curve. RESULTS: Mean CT Severity Index
      was 5.1+/-2.8 (mean +/- standard deviation on a scale of 0 to 10) for the severe
      acute pancreatitis group vs. 3.8+/-2.7 for the mild acute pancreatitis group
      (P=0.230). The CT Severity Index for the children who were not hospitalized at
      the Pediatric Special Care Unit was 2.2+/-2.2 vs. 5.6+/-2.4 for the group
      hospitalized at the Pediatric Special Care Unit (P=0.001). Only parenchymal
      necrosis >30% was associated with severe acute pancreatitis (P=0.021). A CT
      Severity Index >=3 has a sensitivity of 89% and specificity of 72% to predict
      need for admission to the Pediatric Special Care Unit. None of the Revised
      Atlanta Classification categories was associated with severe acute pancreatitis
      or admission to the Pediatric Special Care Unit. CONCLUSION: A CT Severity Index
      >=3 in children with acute pancreatitis who require CT assessment based on
      clinical criteria is associated with the need for admission to the Pediatric
      Special Care Unit. We found that pancreatic necrosis greater than 30% is the only
      tomographic parameter related to severe acute pancreatitis. New studies with a
      greater sample size are necessary to confirm this result.

PMID- 29468367
TI  - Diagnosis, treatment and outcome of hepatic venous outflow obstruction in
      paediatric liver transplantation: 24-year experience at a single centre.
AB  - BACKGROUND: Hepatic venous outflow obstruction after paediatric liver
      transplantation is an unusual but critical complication. OBJECTIVES: To review
      the incidence, diagnosis and therapeutic modalities of hepatic venous outflow
      obstruction from a large national liver transplant unit. MATERIALS AND METHODS:
      During the period from October 1992 to March 2016, 917 liver transplant
      procedures were performed with all types of grafts in 792 children. Transplants
      suspected to have early or delayed venous outflow obstruction were confirmed by
      percutaneous venography or surgical revision findings. Therapeutic intervention,
      recurrence and outcome were evaluated. RESULTS: Twenty-six of 792 children (3.3%)
      experienced post-transplant hepatic venous outflow obstruction. These patients
      had been diagnosed from 1 day to 8.75 years after transplantation. Six occurred
      during the early post-transplant period; in three of them, the graft was lost.
      Seventeen patients were initially treated by balloon angioplasty with success; 11
      of these experienced recurrences. Four stents were implanted; one was complicated
      by definitive occlusion. Three of the five surgical revisions were successful.
      The initial stenosis involved the inferior vena cava in 10 grafts, in isolation
      or associated with hepatic vein involvement. Mean follow-up was 79 months after
      transplantation. Eight grafts were lost. CONCLUSION: Acute postoperative hepatic
      venous outflow obstruction was associated with poor prognosis. Diagnostic
      venography should be performed if there is any suspicion of venous outflow
      obstruction, even if first-line examinations are normal. Stenosis frequently
      involved the inferior vena cava. Angioplasty was a safe and efficient treatment
      for venous outflow obstruction despite frequent recurrence.

PMID- 29468368
TI  - Transitions of Developmental Trajectories of Depressive Symptoms Between Junior
      and Senior High School Among Youths in Taiwan: Linkages to Symptoms in Young
      Adulthood.
AB  - We investigated the heterogeneous developmental trajectories of depressive
      symptoms in junior and senior high school, the transitions to different
      trajectories after entering senior high school, and the linkages to the
      development of depressive symptoms in early adulthood among Taiwanese
      adolescents. An eight-wave longitudinal data set was analyzed, including 2687
      Taiwanese adolescents (51.2% boys, M age = 14.3 at first wave). Using a manual
      three-step latent transition growth mixture model, we found that a three-class
      solution fit the data for both junior high school (termed high-improving,
      cumulative, and JS-low-stable) and senior high school period (termed heightening,
      moderate-stable, and HS-low-stable). The depressive symptoms of most individuals
      maintained at a low level (i.e., low-stable) from adolescence to early adulthood;
      however, nearly a quarter of the adolescents reported depressive symptoms that
      were moderately or highly severe in senior high school and beyond. More than 30%
      of the participants experienced transitioning into a different developmental
      trajectory between junior and senior high school. When perceiving a higher level
      of paternal behavioral control, adolescents categorized in the high-improving
      class in junior high school would have a higher chance to transition to the
      moderate-stable class than to HS-low-stable class in senior high school.
      Adolescent boys and girls did not differ in the probability of transitioning
      between trajectories across junior and senior high school. However, a clear and
      consistent pattern of symptoms between late adolescence and early adulthood was
      not observed. These results help elucidate the heterogeneity and fluidity
      associated with the development of depressive symptoms between early adolescence
      and early adulthood in light of school transition among youths in Taiwan.

PMID- 29468370
TI  - A letter of reply to: Can the gastrointestinal microbiota be modulated by dietary
      fibre to treat obesity? Davis, H.C. Ir J Med Sci (2017).
      https://doi.org/10.1007/s11845-017-1686-9.

PMID- 29468371
TI  - Prenatal parental designing of children and the problem of acceptance.
AB  - Seemingly ever improving medical technology and techniques portend the
      possibility of prenatally enhancing otherwise healthy, normal children-seamlessly
      enhancing or adding to a child's natural abilities and characteristics. Though
      parents normally engage in enhancing children, i.e., child rearing, these
      technologies present radically new possibilities. This sort of enhancement, I
      argue, is morally problematic for the parent: the expectations of the enhancing
      parent necessarily conflict with attitudes of acceptance that moral parenting
      requires. Attitudes of acceptance necessitate that parents are open to the
      essentially-individual choices of the child that will determine the kind of
      person he or she becomes. However, the intentional act of enhancing contradicts
      this openness by setting expectations on who the child becomes. Because of this,
      there is strong moral weight against parents' prenatally enhancing their
      children.

PMID- 29468369
TI  - Role of endoplasmic reticulum stress in 12/15-lipoxygenase-induced retinal
      microvascular dysfunction in a mouse model of diabetic retinopathy.
AB  - AIMS/HYPOTHESIS: Our earlier studies have established the role of 12/15
      lipoxygenase (LO) in mediating the inflammatory reaction in diabetic retinopathy.
      However, the exact mechanism is still unclear. The goal of the current study was
      to identify the potential role of endoplasmic reticulum (ER) stress as a major
      cellular stress response in the 12/15-LO-induced retinal changes in diabetic
      retinopathy. METHODS: We used in vivo and in vitro approaches. For in vivo
      studies, experimental diabetes was induced in wild-type (WT) mice and 12/15-Lo
      (also known as Alox15) knockout mice (12/15-Lo-/-); ER stress was then evaluated
      after 12-14 weeks of diabetes. We also tested the effect of intravitreal
      injection of 12-hydroxyeicosatetraenoic acid (HETE) on retinal ER stress in WT
      mice and in mice lacking the catalytic subunit of NADPH oxidase, encoded by Nox2
      (also known as Cybb) (Nox2-/- mice). In vitro studies were performed using human
      retinal endothelial cells (HRECs) treated with 15-HETE (0.1 MUmol/l) or vehicle,
      with or without ER stress or NADPH oxidase inhibitors. This was followed by
      evaluation of ER stress response, NADPH oxidase expression/activity and the
      levels of phosphorylated vascular endothelial growth factor receptor-2 (p-VEGFR2)
      by western blotting and immunoprecipitation assays. Moreover, real-time imaging
      of intracellular calcium (Ca2+) release in HRECs treated with or without 15-HETE
      was performed using confocal microscopy. RESULTS: Deletion of 12/15-Lo
      significantly attenuated diabetes-induced ER stress in mouse retina. In vitro, 15
      HETE upregulated ER stress markers such as phosphorylated RNA-dependent protein
      kinase-like ER-regulated kinase (p-PERK), activating transcription factor 6
      (ATF6) and protein disulfide isomerase (PDI) in HRECs. Inhibition of ER stress
      reduced 15-HETE-induced-leucocyte adhesion, VEGFR2 phosphorylation and NADPH
      oxidase expression/activity. However, inhibition of NADPH oxidase or deletion of
      Nox2 had no effect on ER stress induced by the 12/15-LO-derived metabolites both
      in vitro and in vivo. We also found that 15-HETE increases the intracellular
      calcium in HRECs. CONCLUSIONS/INTERPRETATION: ER stress contributes to 12/15-LO
      induced retinal inflammation in diabetic retinopathy via activation of NADPH
      oxidase and VEGFR2. Perturbation of calcium homeostasis in the retina might also
      play a role in linking 12/15-LO to retinal ER stress and subsequent microvascular
      dysfunction in diabetic retinopathy.

PMID- 29468372
TI  - Potential Impact of Helicobacter Pylori on Hepatic Encephalopathy
      Pathophysiology.

PMID- 29468373
TI  - Exploring Symptom Severity, Illness Perceptions, Coping Styles, and Well-Being in
      Gastroparesis Patients Using the Common Sense Model.
AB  - AIMS: This study aimed to examine the relationships between gastroparesis symptom
      severity, illness perceptions, coping styles, quality of life (QoL), and
      psychological distress in patients with gastroparesis, guided by the common sense
      model. METHODS: One hundred and seventy-nine adults with gastroparesis (165
      females, 14 males; mean age 41.82 years) completed an online questionnaire. The
      Gastroparesis Cardinal Symptom Index was used to measure gastroparesis symptom
      severity, QoL was explored using the PAGI-QOL, illness perceptions were measured
      using the Brief Illness Perception Questionnaire, the Carver Brief COPE scale
      assessed coping styles, and psychological distress was investigated using the
      DASS21. RESULTS: Structural equation modeling resulted in a final model with
      excellent fit. Gastroparesis symptom severity directly influenced illness
      perceptions (beta = .52, p < .001) and QoL (beta = .30, p < .001). Illness
      perceptions directly influenced maladaptive coping (beta = - .64, p < .001),
      psychological distress (beta = - .32, p < .001), and QoL (beta = .30, p = .01).
      Maladaptive coping directly influenced psychological distress (beta = .62, p <
      .001), which in turn had a direct influence on QoL (beta = - .38, p < .001).
      CONCLUSIONS: The final model showed that the influence of gastroparesis symptom
      severity on psychological distress was fully mediated by illness perceptions,
      while the influence on QoL was partially mediated by illness perceptions. The
      study provides guidance for the development of psychological interventions
      targeted toward improving mediating psychological factors.

PMID- 29468374
TI  - Fecal Calprotectin in Assessing Endoscopic and Histological Remission in Patients
      with Ulcerative Colitis.
AB  - BACKGROUND: Persistent active endoscopic and histological inflammation is
      associated with poorer outcomes in ulcerative colitis (UC). Fecal calprotectin is
      a surrogate marker of endoscopic and histological remission. AIMS: To confirm the
      correlation between fecal calprotectin and endoscopic or histological disease
      activity and to define the optimal cutoff value to detect endoscopic and
      histological remission. METHODS: From a prospectively maintained database, we
      analyzed 61 UC patients who had fecal calprotectin measurement and endoscopy
      performed within 1 month. Endoscopic activity was graded using the Mayo
      endoscopic subscore (MES). Histological remission was defined as normal histology
      or quiescent histological activity. RESULTS: Eighteen patients (29.5%) and five
      patients (8.1%) had endoscopic remission defined as MES <= 1 or MES = 0,
      respectively. We observed a significantly lower median level of fecal
      calprotectin in patients with endoscopic remission than those with endoscopic
      activity for both definition of endoscopic remission, i.e., MES <= 1 (158 vs 490
      ug/g, p = 0.0005) or MES = 0 (94 vs 414 ug/g, p = 0.013). Seven patients (11.5%)
      were in histological remission. They had a lower median level of fecal
      calprotectin than those with active histological inflammation (107 vs 416 ug/g, p
      = 0.016). Using a ROC curve, fecal calprotectin < 250 ug/g predicted endoscopic
      remission (MES <= 1) with a sensitivity of 67% and specificity of 77%, while
      fecal calprotectin < 200 ug/g predicted histological remission with a sensitivity
      of 71% and specificity of 76%. CONCLUSION: Fecal calprotectin level correlated
      with both endoscopic activity and histological activity and is a reliable
      biomarker in assessing mucosal healing in UC.

PMID- 29468375
TI  - Heterotopic Pancreas: A Rare Cause of Gastrointestinal Bleeding in Children.

PMID- 29468376
TI  - Gastric Per Oral Endoscopic Myotomy (G-POEM) for the Treatment of Refractory
      Gastroparesis: Early Experience.
AB  - BACKGROUND: Gastric per oral endoscopic myotomy (G-POEM) of the pylorus is a
      technique that is recently being used to treat gastroparesis. Our aim was to
      report our experience in performing G-POEM for refractory gastroparesis of
      different etiologies and determine symptom improvement. METHODS: Thirteen
      patients undergoing G-POEM are reported. Pre- and post-procedure gastric emptying
      study (GES) and PAGI-SYM for symptom severity were obtained. Patients underwent G
      POEM by creating a submucosal tunnel starting in the greater curvature of the
      distal antrum and extending it to the beginning of the duodenal bulb, followed by
      a full thickness pyloromyotomy. RESULTS: All 13 gastroparesis patients
      successfully underwent G-POEM (one diabetic [DGp], four idiopathic [IGp], eight
      postsurgical [PSGp]). Postsurgical patients included 4 s/p esophagectomy for
      esophageal cancer, 3 s/p Nissen fundoplication, and 1 s/p esophagectomy for
      achalasia. There were no procedure-related side effects. Of 11 patients
      completing follow-up questionnaires, eight were improved subjectively (four
      patients reported considerably better, four patients somewhat better, one
      unchanged, and two worse). Individual symptom severity scores tended to improve,
      particularly vomiting, retching, and loss of appetite. Of six patients that had
      post-G-POEM GES; GES improved in four, unchanged in one, and worsened in one).
      CONCLUSIONS: G-POEM for treatment of refractory gastroparesis appears to be a
      feasible and safe technique that can be successfully performed in patients with a
      variety of etiologies including different types of postsurgical gastroparesis.
      Our initial experience suggests that the majority of patients report some
      improvement in symptoms, particularly symptoms of vomiting, retching, and loss of
      appetite. Further experience is needed to determine the efficacy and safety of G
      POEM and predict those who best respond to this treatment.

PMID- 29468378
TI  - Achalasia Patients Are at Nutritional Risk Regardless of Presenting Weight
      Category.
AB  - BACKGROUND: Achalasia is an esophageal motor disorder that leads to swallowing
      dysfunction and weight loss. Nutritional risk in achalasia patients is not well
      defined. AIMS: The aims of this study were to define baseline body mass index
      (BMI), changes in weight, and nutritional risk over time in a large cohort of
      achalasia patients. METHODS: This was a retrospective cohort study of achalasia
      patients at a tertiary care center with documented BMI, symptom severity as per
      Eckardt score, and nutritional risk assessment as per the Malnutrition Universal
      Screening Tool, which considers BMI, degree of recent weight loss, and acuity of
      disease. RESULTS: Among the 337 patients presenting for achalasia management, 179
      had confirmed disease. Upon presentation 69.8% of patients were classified as
      overweight or obese. Using the Malnutrition Universal Screening Tool, we found
      50% of patients to be at moderate or high risk for malnutrition at presentation.
      Eckardt score (OR 1.15, 95% CI 1.05-1.26), duration of disease (OR for each
      additional month 1.04, 95% CI 1.01-1.08), and female gender (OR 1.76, 95% CI 1.02
      3.03) were independent predictors of increased risk for malnutrition. Nutrition
      risk score decreased after therapy in 93.3% of patients. CONCLUSIONS: Despite a
      high prevalence of overweight and obese status in achalasia patients, many are at
      risk of developing nutritional complications secondary to rapid weight loss. This
      risk frequently resolves post-treatment. Regardless of baseline BMI, we recommend
      all patients undergo nutritional assessment to identify high-risk patients who
      may benefit from dietary intervention and expedited therapy.

PMID- 29468377
TI  - Adenoma Detection Rate in Asymptomatic Patients with Positive Fecal
      Immunochemical Tests.
AB  - BACKGROUND AND AIMS: The adenoma detection rate (ADR) is a powerful measure of
      screening colonoscopy quality. Patients who undergo colonoscopy for the
      evaluation of a positive fecal immunochemical test (FIT) have increased
      prevalence of colorectal neoplasia, but it is not known whether separate quality
      benchmarks are required. The aim of this study was to compare the conventional
      ADR to the ADR of colonoscopies performed for the evaluation of positive FIT, in
      asymptomatic average-risk patients. METHODS: Patients >= 50 years old who
      underwent colonoscopy for the evaluation of a positive FIT between January 1,
      2013, and July 31, 2014, at a tertiary Veterans Affairs Medical Center were
      identified. FIT performed for any indication other than average-risk screening
      was excluded. The comparison group included average-risk patients >= 50 years old
      undergoing screening colonoscopy during the same time frame. The two groups were
      compared for ADR, advanced neoplasm [adenoma >= 10 mm, tubulovillous, high-grade
      dysplasia, CRC, sessile serrated polyp (SSP) >= 10 mm], CRC, and SSP detection
      after propensity score adjustment using a logistic regression model adjusted for
      endoscopist. RESULTS: There were 207 patients in the FIT group and 601 in the
      screening colonoscopy comparison group. After propensity score adjustment, ADR
      (72.9 vs. 50.0%, p = 0.003), number of adenomas per colonoscopy (3.3 +/- 3.6 vs.
      1.4 +/- 2.3, p = 0.033), and advanced neoplasm detection rate (32.4 vs. 11.0%, p
      < 0.0001) were significantly higher in the FIT group. There were no significant
      differences in the number of CRC and the SSP detection rate. CONCLUSIONS: In this
      cohort of average-risk Veterans, the ADR of colonoscopies performed for the
      evaluation of a positive FIT was higher than the ADR of screening colonoscopies.
      Patients with a positive FIT also had significantly more adenomas per colonoscopy
      and advanced neoplasms. These findings suggest that the quality of colonoscopies
      performed for a positive FIT is insufficiently assessed by the conventional ADR
      and requires additional quality metrics.

PMID- 29468379
TI  - Letter to the editors regarding the article entitled: "Cardiothoracic injuries
      after CardioPump CPR: a report of two cases and review of the literature" by
      Kolopp et al.

PMID- 29468380
TI  - Guidelines examination of victims of sexual assault harmonization of forensic and
      medico-legal examination of persons.
AB  - Sexual assault is a complex situation with medical, psychological, and legal
      aspects. Forensic experts play a major role in terms of forensic and
      gynecological medical examination and evidence collection in order to maintain
      the chain of custody. Victims should be examined by a specially trained medico
      legal examiner in order to avoid multiple examinations in the surroundings that
      do not meet minimum health standards. The evolution and treatment of sexual
      assault victims are time-intensive and should optimally be provided by a team
      that includes a forensic medical doctor. These guidelines will be of interest to
      forensic medical doctors who will have responsibility for the examination and
      assessment of victims of sexual violence and can be used as a day-to-day service
      document and/or a guide to develop health service for victims of sexual violence.

PMID- 29468382
TI  - Immunohistochemistry for transcription factor T-Pit as a tool in diagnostics of
      corticotroph pituitary tumours.

PMID- 29468381
TI  - Massively parallel sequencing-enabled mixture analysis of mitochondrial DNA
      samples.
AB  - The mitochondrial genome has a number of characteristics that provide useful
      information to forensic investigations. Massively parallel sequencing (MPS)
      technologies offer improvements to the quantitative analysis of the mitochondrial
      genome, specifically the interpretation of mixed mitochondrial samples. Two
      person mixtures with nuclear DNA ratios of 1:1, 5:1, 10:1, and 20:1 of
      individuals from different and similar phylogenetic backgrounds and three-person
      mixtures with nuclear DNA ratios of 1:1:1 and 5:1:1 were prepared using the
      Precision ID mtDNA Whole Genome Panel and Ion Chef, and sequenced on the Ion PGM
      or Ion S5 sequencer (Thermo Fisher Scientific, Waltham, MA, USA). These data were
      used to evaluate whether and to what degree MPS mixtures could be deconvolved.
      Analysis was effective in identifying the major contributor in each instance,
      while SNPs from the minor contributor's haplotype only were identified in the
      1:1, 5:1, and 10:1 two-person mixtures. While the major contributor was
      identified from the 5:1:1 mixture, analysis of the three-person mixtures was more
      complex, and the mixed haplotypes could not be completely parsed. These results
      indicate that mixed mitochondrial DNA samples may be interpreted with the use of
      MPS technologies.

PMID- 29468383
TI  - Effect of Levocarnitine on the Therapeutic Efficacy of Conventional Therapy in
      Children with Dilated Cardiomyopathy: Results of a Randomized Trial in 29
      Children.
AB  - BACKGROUND: The effect of levocarnitine supplementation has not been evaluated in
      children with dilated cardiomyopathy (DCM). OBJECTIVE: The aim of this study was
      to explore the effect of oral levocarnitine supplementation in pediatric patients
      with DCM. METHODS: Twenty-nine children with DCM (17 male, 12 female, aged 1
      month to 13 years) were divided into two groups according to a simple
      randomization: control group (n = 10) and experimental group (n = 19). All
      children were given oral hydrochlorothiazide, enalapril, and spironolactone;
      additionally, patients with cardiac function of NYHA grade IV were given oral
      digoxin, and patients with intractable heart failure were given intravenous
      dopamine and dobutamine. When cardiac function was restored to NYHA grade II-III,
      patients were given oral metoprolol. Patients in the experimental group received
      add-on treatment with oral levocarnitine solution (50-100 mg/kg/day). Patients
      were followed up at 1, 3, 6 and 12 months. Left ventricular ejection fraction
      (EF), short axis shortening (FS), and left atrium (LA) and left ventricle (LV)
      diameters were measured at different times during the follow-up. RESULTS: The
      children with DCM were followed up for 1 year. Cardiac function was significantly
      improved in the experimental group compared with the control group. Specifically,
      the EF and FS were increased (p < 0.05), the LA and LV diameters were reduced (p
      < 0.05), and the EF was increased more significantly in the experimental group
      than in the control group (p < 0.05). CONCLUSIONS: Oral levocarnitine solution
      appeared to enhance the therapeutic efficacy of conventional therapy in children
      with DCM.

PMID- 29468384
TI  - Redirection of neuroblast migration from the rostral migratory stream into a
      lesion in the prefrontal cortex of adult rats.
AB  - Clinical treatment of structural brain damage today is largely limited to
      symptomatic approaches and the avoidance of secondary injury. However, neuronal
      precursor cells are constantly produced within specified regions of the mammalian
      brain throughout life. Here we evaluate the potential of the known
      chemoattractive properties of the glycoprotein laminin on neuroblasts to relocate
      the cells into damaged brain areas. Injection of a thin laminin tract, leading
      from the rostral migratory stream to an excitotoxic lesion within the medial
      prefrontal cortex of rats, enabled neuroblasts to migrate away from their
      physiological route towards the olfactory bulb into the lesion site. Once they
      reached the damaged tissue, they migrated further in a non-uniform orientation
      within the lesion. Furthermore, our data indicate that the process of diverted
      migration is still active 6 weeks after the treatment and that at least some of
      the neuroblasts are capable of maturing into adult neurons.

PMID- 29468385
TI  - Comments on Marken and Shaffer: The power law of movement: an example of a
      behavioral illusion.
AB  - Many researchers who have studied movements along curved paths, under a variety
      of conditions, by different organisms, mostly human but a couple with non-human
      organisms, have found a consistent form of relation between the tangential (along
      track) instantaneous velocity V and the local radius of curvature R. The
      consistent relation is that V ~ cR k , where k is a constant less than unity,
      often near 0.33 but sometimes far from 0.33, and c is a proportionality constant
      appropriate to the organism and the situation (see Zago, Matic, Flash, et al.
      (2017) for many examples in which the power law holds with widely varying values
      of the power, as well as cases of simple systems for which everything can be
      calculated exactly and in which the power law fails badly). Marken and Shaffer
      (Exp Brain Res 235:1835-1842; 2017), following a challenge by Gomez-Marin to see
      whether it is possible to use Perceptual Control Theory (Powers 1973/2005) to
      explain the power law results (Alex Gomez-Marin posting to
      CSGnet@lists.illinois.edu 2016.05.03), claim to have found a mathematical
      argument that proves the true exponent of the power relating velocity and radius
      of curvature always to be 1/3. They say that deviations from this value occur
      because researchers have omitted a critical correction "cross-product" factor
      that the authors label "D". This note questions the logic of the analysis offered
      by Marken and Shaffer, and argues that even had the analysis been correct, it
      would not affect future research into the reasons why and when the power law is
      observed and the circumstances that determine the value of the power found when
      it is observed.

PMID- 29468386
TI  - Muscle spindle thixotropy affects force perception through afferent-induced
      facilitation of the motor pathways as revealed by the Kohnstamm effect.
AB  - This study was designed to explore the effects of intrafusal thixotropy, a
      property affecting muscle spindle sensitivity, on the sense of force. For this
      purpose, psychophysical measurements of force perception were performed using an
      isometric force matching paradigm of elbow flexors consisting of matching
      different force magnitudes (5, 10 and 20% of subjects' maximal voluntary force).
      We investigated participants' capacity to match these forces after their
      indicator arm had undergone voluntary isometric conditioning contractions known
      to alter spindle thixotropy, i.e., contractions performed at long ('hold long')
      or short muscle lengths ('hold short'). In parallel, their reference arm was
      conditioned at the intermediate muscle length ('hold-test') at which the
      matchings were performed. The thixotropy hypothesis predicts that estimation
      errors should only be observed at low force levels (up to 10% of the maximal
      voluntary force) with overestimation of the forces produced following 'hold
      short' conditioning and underestimation following 'hold long' conditioning. We
      found the complete opposite, especially following 'hold-short' conditioning where
      subjects underestimated the force they generated with similar relative error
      magnitudes across force levels. In a second experiment, we tested the hypothesis
      that estimation errors depended on the degree of afferent-induced facilitation
      using the Kohnstamm phenomenon as a probe of motor pathway excitability. Because
      the stronger post-effects were observed following 'hold-short' conditioning, it
      appears that the conditioning-induced excitation of spindle afferents leads to
      force misjudgments by introducing a decoupling between the central effort and the
      cortical motor outputs.

PMID- 29468387
TI  - Assessing the equivalence of Web-based and paper-and-pencil questionnaires using
      differential item and test functioning (DIF and DTF) analysis: a case of the Four
      Dimensional Symptom Questionnaire (4DSQ).
AB  - PURPOSE: Many paper-and-pencil (P&P) questionnaires have been migrated to
      electronic platforms. Differential item and test functioning (DIF and DTF)
      analysis constitutes a superior research design to assess measurement equivalence
      across modes of administration. The purpose of this study was to demonstrate an
      item response theory (IRT)-based DIF and DTF analysis to assess the measurement
      equivalence of a Web-based version and the original P&P format of the Four
      Dimensional Symptom Questionnaire (4DSQ), measuring distress, depression,
      anxiety, and somatization. METHODS: The P&P group (n = 2031) and the Web group (n
      = 958) consisted of primary care psychology clients. Unidimensionality and local
      independence of the 4DSQ scales were examined using IRT and Yen's Q3. Bifactor
      modeling was used to assess the scales' essential unidimensionality. Measurement
      equivalence was assessed using IRT-based DIF analysis using a 3-stage approach:
      linking on the latent mean and variance, selection of anchor items, and DIF
      testing using the Wald test. DTF was evaluated by comparing expected scale scores
      as a function of the latent trait. RESULTS: The 4DSQ scales proved to be
      essentially unidimensional in both modalities. Five items, belonging to the
      distress and somatization scales, displayed small amounts of DIF. DTF analysis
      revealed that the impact of DIF on the scale level was negligible. CONCLUSIONS:
      IRT-based DIF and DTF analysis is demonstrated as a way to assess the equivalence
      of Web-based and P&P questionnaire modalities. Data obtained with the Web-based
      4DSQ are equivalent to data obtained with the P&P version.

PMID- 29468388
TI  - Sorption of benzene derivatives onto a humic acid-zeolitic tuff adduct.
AB  - The sorption of some benzene derivatives: o-xylene, toluene, phenol, benzyl
      alcohol, resorcinol and hydroquinone onto a zeolitic tuff-humic acid adduct (PCT
      ImHA) was analysed by batch technique at 25  degrees C and neutral pH. PCT-ImHA
      was prepared by binding leonardite-extracted humic acids (HA) to a zeolitic tuff
      sample rich in phillipsite and chabazite and enriched with Ca2+ by cation
      exchange (Ca-PCT). The HA calcium salts were gently mixed with wet Ca-PCT; then,
      the mixture was heated at 330  degrees C for 1.5 h. An adduct with almost 2% of
      HA was obtained. The experimental data were well fitted by the Langmuir
      adsorption isotherm and showed that saturation capacity (qMax) increased with the
      octanol-water repartition coefficient (KO-W). The comparison with previous data
      on sorption onto immobilised HA highlights that qMax values for PCT-ImHA are far
      higher than the sum of the contributions of the two separate components.

PMID- 29468389
TI  - The '333' integrated strategy for effective pollution control and its application
      to the heavily polluted Jialu River in north China.
AB  - In this study, an integrated approach named the '333' strategy was applied to
      pollution control in the Jialu River, in northern China, which is heavily
      burdened with anthropogenic pollution. Due to a deficiency of the natural
      ecological inflow, the Jialu River receives predominantly industrial and
      municipal effluent. The '333' strategy is composed of three steps of pollution
      control including industrial point-source pollution control, advanced treatment
      of municipal wastewater, and ecological restoration; three increased stringency
      emission standards; and three stages of reclamation. Phase 1 of the '333'
      strategy focuses on industrial point-source pollution control; phase 2 aims to
      harness municipal wastewater and minimize sewage effluents using novel techniques
      for advanced water purification; phase 3 of the '333' strategy focuses on the
      further purification of effluents flowing into Jialu River with the employment of
      an engineering-based ecological restoration project. The application of the '333'
      strategy resulted in the development of novel techniques for water purification
      including modified magnetic resins (NDMP resin), a two-stage internal circulation
      anaerobic reactor (IC reactor) and an ecological restoration system. The results
      indicate that water quality in the river was significantly improved, with
      increased concentrations of dissolved oxygen (DO), as well as reduction of COD by
      42.8% and NH3-N by 61.4%. In addition, it was observed that the total population
      of phytoplankton in treated river water notably increased from only one prior to
      restoration to 8 following restoration. This system also provides a tool for
      pollution control of other similar industrial and anthropogenic source polluted
      rivers.

PMID- 29468390
TI  - Impacts of sewer deposits on the urban river sediment after rainy season and
      bioremediation of polluted sediment.
AB  - Impacts of deposits discharged from a municipal pipe on urban river sediment were
      investigated in the Hucang River in Tianjin, China. At the outlet of the pump
      station, the average concentrations of total nitrogen (TN), total phosphorus
      (TP), and total organic carbon (TOC) in the sediment increased sharply from 2390,
      799, and 14,600 mg/kg to 6500, 3700, and 153,000 mg/kg, respectively, and
      remained stable at high level after the rainy season. A portion of pollutants
      would migrate along the river, and the concentration was usually in a negative
      relationship with the distance. The average Shannon-Wiener value on the upstream
      section was higher than those on the downstream sections. This revealed that the
      deposits discharged decreased the bacterial diversity in the sediment, and high
      concentrations of pollutants may markedly change the bacterial community
      structure in the sediment. To reduce the pollution of the urban river after rainy
      season, four kinds of microbial consortiums A (Zhangda), B (Aiersi), C (Qinghe),
      and D (Inpipe) were applied to bioremediate the polluted sediment in lab scale.
      Bioaugmentation with microbial consortium A showed good performance on the
      bioremediation of the polluted sediment. The average removal efficiency of TN,
      TP, and organic matter reached 35.5, 43.7, and 39.1%, respectively, after 22 days
      of treatment. Moreover, the bacterial evenness and diversity in the sediment
      markedly increased, indicating that the microbial environment was more favourable
      after bioaugmentation and sustainable development would be guaranteed. This study
      improves our understanding of the impacts of deposits discharged from a
      stormwater drain system on urban river sediment, and explores the effectiveness
      of bioaugmentation for the bioremediation of polluted sediment, which will
      provide the basis of sewer deposit pollution control.

PMID- 29468391
TI  - Intercropping efficiency of four arsenic hyperaccumulator Pteris vittata
      populations as intercrops with Morus alba.
AB  - Soils that are slightly or moderately contaminated with arsenic (As) can be
      safely utilized by intercropping As hyperaccumulator Pteris vittata with cash
      crops. Introducing hyperaccumulators into crop planting systems results in the
      alleviation of the adverse effects of As and competition effect for resources.
      The balance between these two effects determines intercropping efficiency. The
      effect of using different hyperaccumulator populations on such balance is the
      focus of this study. Through a tank experiment, four P. vittata populations were
      compared on the basis of their intercropping efficiencies and physiological and
      morphological characteristics. The evaluation of the intercropping efficiency of
      P. vittata was mainly based on the capabilities of the species to promote growth
      and decrease As concentrations in intercropped Morus alba. Two populations of P.
      vittata were appropriate for intercropping with M. alba, with the alleviation
      effect of As harm as the main effect on the intercropping system. These
      populations showed extensive root overlap with M. alba and efficient uptake of
      bioavailable As, thus depleting As in the rhizosphere and lowering As risk. After
      different P. vittata populations were used, varied interspecific interactions
      were observed. Root overlap and aboveground morphological parameters are the key
      factors determining intercropping efficiency among P. vittata populations.

PMID- 29468392
TI  - Hydrogen sulfide regulates the levels of key metabolites and antioxidant defense
      system to counteract oxidative stress in pepper (Capsicum annuum L.) plants
      exposed to high zinc regime.
AB  - In the present experiment, we aimed to test the impact of hydrogen sulfide (H2S)
      on growth, key oxidant such as hydrogen peroxide, mineral elements, and
      antioxidative defense in Capia-type red sweet pepper (Capsicum annuum L.) plants
      subjected to high concentration of zinc (Zn). A factorial experiment was designed
      with two Zn levels (0.05 and 0.5 mM) and 0.2 mM sodium hydrosulfide (NaHS) as a
      donor of H2S supplied in combination plus nutrient solution through the root
      zone. High level of Zn led to reduce dry mass, chlorophyll pigments, fruit yield,
      leaf maximum fluorescence, and relative water content, but enhanced endogenous
      hydrogen peroxide (H2O2), free proline, malondialdehyde (MDA), electrolyte
      leakage (EL), H2S, as well as the activities of peroxidase (POD), catalase (CAT),
      and superoxide dismutase (SOD) enzymes. Exogenously applied NaHS significantly
      enhanced plant growth, fruit yield, water status, the levels of H2S and proline
      as well as the activities of different antioxidant enzymes, while it
      significantly suppressed EL, MDA, and H2O2 contents in the pepper plants
      receiving low level Zn. NaHS application to the control plants did not
      significantly change all these parameters tested except the dry matter which
      increased significantly. High Zn regime led to increase intrinsic Zn levels in
      the leaves and roots, but it lowered leaf nitrogen (N), phosphorus (P), and iron
      (Fe) concentrations. However, NaHS reduces the Zn conc. and enhances Fe and N in
      leaf and root organs. It can be concluded that NaHS can mitigate the harmful
      effects of Zn on plant growth particularly by lowering the concentrations of
      H2O2, Zn, EL, and MDA, and enhancing the activities of enzymatic antioxidants and
      levels of essential nutrients in pepper plants.

PMID- 29468394
TI  - Emission and performance analysis on the effect of exhaust gas recirculation in
      alcohol-biodiesel aspirated research diesel engine.
AB  - In this study, the effect of blending pentanol to biodiesel derived from mahua
      oil on emissions and performance pattern of a diesel engine under exhaust gas
      recirculation (EGR) mode was examined and compared with diesel. The purpose of
      this study is to improve the feasibility of employing biofuels as a potential
      alternative in an unmodified diesel engine. Two pentanol-biodiesel blends denoted
      as MOBD90P10 and MOBD80P20 which matches to 10 and 20 vol% of pentanol in
      biodiesel, respectively, were used as fuel in research engine at 10 and 20% EGR
      rates. Pentanol is chosen as a higher alcohol owing to its improved in-built
      properties than the other first-generation alcohols such as ethanol or methanol.
      Experimental results show that the pentanol and biodiesel blends (MOBD90P10 and
      MOBD80P20) have slightly higher brake thermal efficiency (0.2-0.4%) and lower
      brake-specific fuel consumption (0.6 to 1.1%) than that of neat biodiesel
      (MOBD100) at all engine loads. Nitrogen oxide (NOx) emission and smoke emission
      are reduced by 3.3-3.9 and 5.1-6.4% for pentanol and biodiesel blends compared to
      neat biodiesel. Introduction of pentanol to biodiesel reduces the unburned
      hydrocarbon (2.1-3.6%) and carbon monoxide emissions (3.1-4.2%) considerably. In
      addition, at 20% EGR rate, smoke, NOX emissions, and BTE drop by 7.8, 5.1, and
      4.4% respectively. However, CO, HC emissions, and BSFC increased by 2.1, 2.8, and
      3.8%, respectively, when compared to 0% EGR rate.

PMID- 29468393
TI  - Growth performance, metal accumulation and biochemical responses of Palak (Beta
      vulgaris L. var. Allgreen H-1) grown on soil amended with sewage sludge-fly ash
      mixtures.
AB  - Agricultural utilization of sewage sludge (SS) and fly ash (FA) has become both,
      a common practice and an alternative disposal method for these wastes all around
      the world. The present study was conducted to assess the effect and viability of
      co-application of SS and FA (SLASH) in four mixing ratios denoted as A [4 (SS):
      1(FA)], B [4 (SS): 2 (FA)], C [4 (SS): 3 (FA)] and D [4 (SS): 4(FA)] at three
      application rates viz. 20, 40 and 60% (w/w) with agricultural soil on
      biochemical, physiological and growth response of Palak (Beta vulgaris L. var.
      Allgreen H-1), a commonly used green leafy vegetable. SLASH amendment modified
      the physico-chemical properties of soil and increased the concentration of heavy
      metals (Cd, Cr, Cu, Fe, Ni, Pb, Zn) in soil and plant parts however, within the
      Indian permissible limit except for Cr, Cd and Zn in shoot. Experimental results
      revealed decrease in morphological and growth parameters such as root and shoot
      length, leaf area, root, shoot biomass etc. Lipid peroxidation, ascorbic acid,
      proline and protein content increased however, total chlorophyll and carotenoid
      content decreased indicating towards heavy metal stress induced biochemical and
      physiological response in Palak plants. Significant increase in yield was seen in
      some of the treatments viz. three mixing ratios B, C and D, with maximum
      increment shown by mixture D at 20 and 40% amendment rate. The results of this
      study suggest that though SLASH amendment for growing Palak improved the physico
      chemical properties of soil amended and also the yield of the plants in some
      treatments, it may not be a good option due to risk of contamination of heavy
      metals such as Cr, Cd and Zn showing higher accumulation.

PMID- 29468395
TI  - Differences in fluorescence characteristics and bioavailability of water-soluble
      organic matter (WSOM) in sediments and suspended solids in Lihu Lake, China.
AB  - The spectral characteristics, spatial distribution, and bioavailability of water
      soluble organic matter (WSOM) in suspended solids and surface sediments of Lihu
      Lake, China, were investigated through excitation-emission matrix spectra and
      parallel factor analysis. The average content of dissolved organic carbon (DOC)
      in the sediments reached 643.28 +/- 58.34 mg C/kg and that in suspended solids
      was 714.87 +/- 69.24 mg C/kg. The fluorescence intensity of WSOM totaled 90.87 +/
      5.65 and 115.42 +/- 8.02 RU/g for the sediments and suspended solids,
      respectively. The DOC and fluorescence intensity of the WSOM showed an increasing
      trend moving from the west to the east of the lake. The WSOM in sediments and
      suspended solids contained two humic-like (C1 and C2) and one tryptophan-like
      (C3) components. These components had different fluorescent peaks and relative
      proportions. In the sediments, the relative proportions of C1, C2, and C3 were
      33.71% +/- 0.71, 26.83% +/- 0.68, and 39.50% +/- 0.71%, respectively. Meanwhile,
      C1 (35.77 +/- 0.84%), C2 (34.07 +/- 0.61%), and C3 (30.16 +/- 0.75%) had similar
      relative percentages in suspended solids. The sediments had a lower humification
      index (3.02 +/- 0.08) than the suspended solids (4.04 +/- 0.15). Exchangeable
      nitrogen for the sediments and suspended solids was dominated by exchangeable
      ammonium nitrogen and soluble organic nitrogen, respectively. WSOM plays an
      important role in migration and transformation of nitrogen in sediments and
      suspended solids. The sediment-derived WSOM exhibited higher lability and
      biological activity than did the suspended solid-derived WSOM. The relative ratio
      of the intensity of protein-like fluorescent component to that of the humic-like
      one can be used as a reference index to evaluate the lability and biological
      activity of WSOM in sediments and suspended solids.

PMID- 29468396
TI  - Vermicompost dose and mycorrhization determine the efficiency of copper
      phytoremediation by Canavalia ensiformis.
AB  - The phytoremediation of copper (Cu)-contaminated sandy soils can be influenced by
      the addition of vermicompost to the soil and the mycorrhization of plants. The
      objective of this study was to evaluate the effects of inoculation with the
      mycorrhizal fungus Rhizophagus clarus and the addition of different doses of
      bovine manure vermicompost on the phytoremediation of a sandy soil with a high Cu
      content using Canavalia ensiformis. Soil contaminated with 100 mg kg-1 Cu
      received five doses of vermicompost and was cultivated with C. ensiformis, with
      and without inoculation with mycorrhizal fungus, and the Cu and nutrients in the
      soil and soil solution were evaluated. The concentrations of Cu and other
      nutrients and the biomass and Cu phytotoxicity in the plants were quantified by
      gauging the photochemical efficiency, concentration of photosynthetic pigments
      and activity of oxidative stress enzymes. The vermicompost increased the soil pH
      and nutrient concentrations and reduced the Cu content of the solution. When the
      vermicompost was applied at a dose equivalent to 80 mg phosphorus (P) kg-1, the
      phytoextraction efficiency was higher, but the phytostabilization efficiency was
      higher for vermicompost doses of 10 and 20 mg P kg-1. The presence of mycorrhizal
      fungi increased Cu phytostabilization, especially at vermicompost doses of 10 and
      20 mg P kg-1. The use of vermicompost at low doses and inoculation with
      mycorrhizal fungi increase the phytostabilization potential of C. ensiformis in
      sandy soil contaminated by Cu.

PMID- 29468397
TI  - Indoor radon concentration in Korea residential environments.
AB  - The purpose of this study is to provide basic data for the evaluation and
      management of health effects with respect to exposure to radon within residential
      environments in South Korea. It is part of a case-control study to develop a
      management plan based on indoor radon exposure levels and assess their impact on
      health. To investigate the long-term cumulative concentration levels of radon,
      599 patients who have respiratory diseases were recruited in South Korea, and
      alpha track detectors were installed in their residences for a period of 3 months
      from mid-2015 to late 2016. A survey was then conducted to determine the factors
      affecting the radon concentration. The radon concentration levels were analyzed
      in conjunction with the survey results. The results show that the arithmetic mean
      of the radon concentrations in domestic residences was in the range of 70.8 +/-
      65.2 Bq/m3. An analysis of covariance (ANCOVA) was performed to identify the
      environmental factors affecting the radon concentration and contributing to
      variations in the residential radon concentration based on the height of the
      residence. The results show that the contribution of the local environmental
      factor to the variation in radon concentration (p < 0.05) was greater than that
      of other environmental factors. Although no statistically significant difference
      was found with regard to the construction year of the building before the control
      (p > 0.05), the same was found with regard to the construction year after the
      control (p < 0.05).

PMID- 29468398
TI  - Characterization, evaluation, and mechanistic insights on the adsorption of
      antimonite using functionalized carbon nanotubes.
AB  - Floating catalytic chemical vapor deposition technique was used for synthesizing
      carbon nanotubes (CNTs) using ferrocene in benzene as the hydrocarbon source. The
      functionalization of CNTs was carried out by oxidation followed by grafting of
      potassium iodide (KI) and mercaptoethanol (HS(CH2)2OH) ligands to produce iodide
      grafted CNTs (CNT-I) and thiol-functionalized CNTs (CNT-SH), respectively. The
      resulting adsorbents have been thoroughly characterized by various techniques.
      Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron
      spectroscopy (XPS) studies revealed the efficient grafting of the ligands.
      Further, their adsorption capacities towards antimonite have been assessed. The
      adsorption kinetics fitted the pseudo-second-order model for both the adsorbents.
      Moreover, the adsorption of Sb(III) followed Langmuir and Freundlich's model. The
      maximum adsorption capacity of CNT-I and CNT-SH for Sb(III) at pH 7 was found to
      be 200 and 140.85 mg/g, respectively. The interference effect of various ions on
      the adsorption of antimonite was studied. A suitable mechanism for Sb(III)
      adsorption has been postulated using TEM, XRD, XPS, and FTIR. The adaptability of
      the adsorbents was demonstrated by the removal capacity of Sb(III) at parts per
      billion levels from nuclear decontamination formulation (NAC) and tap water
      matrix as well.

PMID- 29468399
TI  - Pedotransfer functions of potentially toxic elements in tropical soils cultivated
      with vegetable crops.
AB  - The anthropogenic input of potentially toxic elements (PTEs) from industry,
      agrochemicals, etc., into the environment are of great concern. Models derived
      from pedotransfer functions can provide estimates of the levels of PTEs based on
      soil attributes. Based on the importance of these models in studies in
      contaminated areas, we assessed the concentrations of the reactive contents of
      Ba, Cu, Cr, Ni, Pb, and Zn in soils cultivated with vegetable crops in the state
      of Sao Paulo, Brazil. We also evaluated the influence of chemical and physical
      soil attributes on their reactivity and availability. The reactive contents of
      PTEs represent the fraction of PTEs easily sorbed at the adsorptions sites of
      organic matter, iron hydroxides, or clay. This fraction can supply information
      about the PTE content that is more or less readily released into the soil
      solution. The reactive and available fraction was extracted with 0.43 M HNO3 and
      0.01 M CaCl2, respectively. The proportion of reactivity of metal pools decreased
      in the order of Ba>Zn > Cu > Pb > Ni > Cr. The empirical models were able to
      predict the relationship between the reactive fractions, the pseudototal content,
      and the soil attributes. The available concentrations of Cr, Cu, Ni, and Pb in
      the soils were lower than the limit of quantification, while 3% of the Ba content
      and 1% of the Zn content were available in the soil solution in relation to their
      pseudototal content, suggesting low mobility of these elements in the soil.

PMID- 29468400
TI  - Assessment of groundwater vulnerability by applying the modified DRASTIC model in
      Beihai City, China.
AB  - This study assesses vulnerability of groundwater to pollution in Beihai City,
      China, as a support of groundwater resource protection. The assessment result not
      only objectively reflects potential possibility of groundwater to contamination
      but also provides scientific basis for the planning and utilization of
      groundwater resources. This study optimizes the parameters consisting of natural
      factors and human factors upon the DRASTIC model and modifies the ratings of
      these parameters, based on the local environmental conditions for the study area.
      And a weight of each parameter is assigned by the analytic hierarchy process
      (AHP) to reduce the subjectivity of humans to vulnerability assessment. The
      resulting scientific ratings and weights of modified DRASTIC model (AHP-DRASTLE
      model) contribute to obtain the more realistic assessment of vulnerability of
      groundwater to contaminant. The comparison analysis validates the accuracy and
      rationality of the AHP-DRASTLE model and shows it suits the particularity of the
      study area. The new assessment method (AHP-DRASTLE model) can provide a guide for
      other scholars to assess the vulnerability of groundwater to contamination. The
      final vulnerability map for the AHP-DRASTLE model shows four classes: highest
      (2%), high (29%), low (55%), and lowest (14%). The vulnerability map serves as a
      guide for decision makers on groundwater resource protection and land use
      planning at the regional scale and that it is adapted to a specific area.

PMID- 29468402
TI  - [Effects of written educational material on parental health knowledge depending
      on socioeconomic status : A randomized controlled trial].
AB  - BACKGROUND: The nationwide prevention program "Parent Guide - Growing up Healthy"
      aims to improve parental health knowledge in Germany. At the birth of their first
      child, parents of any socioeconomic status (SES) are provided with written
      educational material that includes relevant health knowledge as well as basic
      information about routine health checkups for children. OBJECTIVES: This study
      aimed at evaluating the program regarding 1) the effects on parental health
      knowledge and parental satisfaction with routine child health checkups, 2) the
      sensitivity of the effects on SES, and 3) parental acceptance of the written
      educational material. MATERIALS AND METHODS: A longitudinal randomized controlled
      trial (RCT) was carried out with 1318 young parents recruited from 14 hospitals
      with maternity clinics in Germany. Parents of the intervention group received
      educational material whereas controls didn't receive material. Respondents
      completed interviews at the child's birth (T0) and first birthday (T1). RESULTS:
      Parental health knowledge at T1 was significantly higher (p = 0.005; partial eta2
      = 0.006) in the intervention group but with a small effect size. The influence of
      the educational material was not moderated by SES (p = 0.456). Satisfaction with
      routine child health checkups did not differ significantly between the groups (p
      = 0.606). Parents showed high acceptance of the parent guide regardless of SES.
      CONCLUSIONS: Written educational material is an effective approach in increasing
      parental health knowledge and has the potential to reach all parents regardless
      of SES. A higher satisfaction with routine child health checkups could not be
      achieved by educational material.

PMID- 29468401
TI  - The Role of the Genitourinary Microbiome in Pediatric Urology: a Review.
AB  - PURPOSE OF REVIEW: In this review, we highlight the effects of the microbiome on
      urologic diseases that affect the pediatric patient. RECENT FINDINGS:
      Perturbations in the urinary microbiome have been shown to be associated with a
      number of urologic diseases affecting children, namely urinary tract infection,
      overactive bladder/urge urinary incontinence, and urolithiasis. Recently,
      improved cultivation and sequencing technologies have allowed for the discovery
      of a significant and diverse microbiome in the bladder, previously assumed to be
      sterile. Early studies aimed to identify the resident bacterial species and
      demonstrate the efficacy of sequencing and enhanced quantitative urine culture.
      More recently, research has sought to elucidate the association between the
      microbiome and urologic disease, as well as to demonstrate effects of
      manipulation of the microbiome on various urologic pathologies. With an improved
      appreciation for the impact of the urinary microbiome on urologic disease,
      researchers have begun to explore the impact of these resident bacteria in
      pediatric urology.

PMID- 29468403
TI  - [E-health and medical devices : Federal Health Gazette Special Issue].

PMID- 29468405
TI  - Efficacy and safety of ripasudil, a Rho-associated kinase inhibitor, in eyes with
      uveitic glaucoma.
AB  - PURPOSE: The purpose of this study was to describe the initial experience,
      efficacy, and safety of ripasudil hydrochloride hydrate (ripasudil), a Rho
      associated kinase inhibitor eye drop, for uveitic glaucoma. METHODS: In this
      retrospective case series, we retrieved the clinical data of 21 eyes from 19
      patients with open-angle uveitic glaucoma who were treated with ripasudil at Kobe
      University Hospital. We analyzed the median intraocular pressure (IOP) reductions
      after ripasudil treatment and collected the information on the adverse events
      that were encountered during the course of this treatment period. RESULTS: The
      causes of uveitis were sarcoidosis (29%), Behcet's disease (14%), Vogt-Koyanagi
      Harada disease (10%), others (15%), and unclassified (33%). Of total, 19 (90%)
      eyes were treated with topical, periocular, and/or systemic steroid therapies.
      The median number of glaucoma medications used before ripasudil treatment was 2,
      and the median follow-up time was 13 months. The median IOPs were 23 mmHg at
      baseline, 16 mmHg at 1 month, and 18 mmHg at 12 months with significant IOP
      reductions of - 3 mmHg at 1 month and - 2 mmHg at 12 months (P = 0.0050). Of
      total, 11 (52%) eyes with an IOP reduction >= 3 mmHg at 1 month (responders)
      showed a significant median IOP decrease at 12 months compared with non
      responders (- 5 versus 0 mmHg, P = 0.0242). Two adverse events were observed:
      rashes on the back and transient conjunctival hyperemia. CONCLUSIONS: Ripasudil
      appears to be safe and substantially reduce IOP in eyes with uveitic glaucoma if
      the eye is a responder. Ripasudil could be an option for the treatment of uveitic
      glaucoma.

PMID- 29468404
TI  - Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of
      [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes.
AB  - PURPOSE: Previous studies demonstrated the utility of [18F]fluoropropyl-(+)
      dihydrotetrabenazine ([18F]FP-(+)-DTBZ) as a positron emission tomography (PET)
      radiotracer for the vesicular monoamine transporter type 2 (VMAT2) to quantify
      beta cell mass in healthy control (HC) and type 1 diabetes mellitus (T1DM)
      groups. Quantification of specific binding requires measurement of non
      displaceable uptake. Our goal was to identify a reference tissue (renal cortex or
      spleen) to quantify pancreatic non-specific binding of [18F]FP-(+)-DTBZ with the
      inactive enantiomer, [18F]FP-(-)-DTBZ. This was the first human study of [18F]FP
      (-)-DTBZ. PROCEDURES: Six HCs and four T1DM patients were scanned on separate
      days after injection of [18F]FP-(+)-DTBZ or [18F]FP-(-)-DTBZ. Distribution
      volumes (VT) and standardized uptake values (SUVs) were compared between groups.
      Three methods for calculation of non-displaceable uptake (VND) or reference SUV
      were applied: (1) use of [18F]FP-(+)-DTBZ reference VT as VND, assuming VND is
      uniform across organs; (2) use of [18F]FP-(-)-DTBZ pancreatic VT as VND, assuming
      that VND is uniform between enantiomers in the pancreas; and (3) use of a scaled
      [18F]FP-(+)-DTBZ reference VT as VND, assuming that a ratio of non-displaceable
      uptake between organs is uniform between enantiomers. Group differences in VT (or
      SUV), binding potential (BPND), or SUV ratio (SUVR) were estimated using these
      three methods. RESULTS: [18F]FP-(-)-DTBZ VT values were different among organs,
      and VT(+) and VT(-) were also different in the renal cortex and spleen. Method 3
      with the spleen to estimate VND (or reference SUV) gave the highest non
      displaceable uptake and the largest HC vs. T1DM group differences. Significant
      group differences were also observed in VT (or SUV) with method 1 using spleen.
      SUV was affected by differences in the input function between groups and between
      enantiomers. CONCLUSIONS: Non-displaceable uptake was different among organs and
      between enantiomers. Use of scaled spleen VT values for VND is a suitable method
      for quantification of VMAT2 in the pancreas.

PMID- 29468406
TI  - Comparison of anterior segment optical coherence tomography angiography and
      fluorescein angiography for iris vasculature analysis.
AB  - PURPOSE: The aim of this study is to perform imaging of irises of different
      colors using spectral domain anterior segment optical coherence tomography
      angiography (AS-OCTA) and iris fluorescein angiography (IFA) and compare their
      effectiveness in examining iris vasculature. METHODS: This is a cross-sectional
      observational clinical study. Patients with no vascular iris alterations and
      different pigmentation levels were recruited. Participants were imaged using OCTA
      adapted with an anterior segment lens and IFA with a confocal scanning laser
      ophthalmoscope (cSLO) adapted with an anterior segment lens. AS-OCTA and IFA
      images were then compared. Two blinded readers classified iris pigmentation and
      compared the percentage of visible vessels between OCTA and IFA images. RESULTS:
      Twenty eyes of 10 patients with different degrees of iris pigmentation were
      imaged using AS-OCTA and IFA. Significantly more visible iris vessels were
      observed using OCTA than using FA (W = 5.22; p < 0.001). Iris pigmentation was
      negatively correlated to the percentage of visible vessels in both imaging
      methods (OCTA, rho = - 0.73, p < 0.001; IFA, rho = - 0.77, p < 0.001). Unlike FA,
      AS-OCTA could not detect leakage of dye, delay, or impregnation. Nystagmus and
      inadequate fixation along with motion artifacts resulted in lower quality images
      in AS-OCTA than in IFA. CONCLUSIONS: AS-OCTA is a new imaging modality which
      allows analysis of iris vasculature. In both AS-OCTA and IFA, iris pigmentation
      caused vasculature imaging blockage, but AS-OCTA provided more detailed iris
      vasculature images than IFA. Additional studies including different iris
      pathologies are needed to determine the most optimal scanning parameters in OCTA
      of the anterior segment.

PMID- 29468408
TI  - Is ICER NICEr?

PMID- 29468407
TI  - Intravenous immunoglobulin for the treatment of intractable cholangitis after
      Kasai portoenterostomy in biliary atresia patients.
AB  - OBJECTIVE: To assess the efficacy of intravenous immunoglobulin (IVIG) as add-on
      treatment for intractable cholangitis (IC) after Kasai portoenterostomy (KPE) in
      biliary atresia (BA) patients. METHODS: 113 BA patients who had one or more
      episodes of cholangitis after KPE were recruited in this study. According to
      whether response to routine conservative treatment, all patients were divided
      into IC group and simple cholangitis (SC) group. Meanwhile, patients with IC
      subdivided into IVIG group and control group according to whether application of
      IVIG. RESULTS: The IC group had higher serum procalcitonin (PCT) (P = 0.014), C
      reactive protein (CRP) (P = 0.023), and gamma-Gltamyltranspeptidase (gamma-GGT)
      (P = 0.031) level than the SC group. The IVIG group had shorter duration of fever
      after treatment (P = 0.011) and length of hospital stay (P = 0.018) than the
      control group. The time until recurrent episode of cholangitis was significant
      longer in IVIG group than in control group (P = 0.019). CONCLUSIONS: IVIG as add
      on treatment may be an effective treatment for the cholangitis acute episode, and
      we conclude by calling for more prospective studies to attest to the role of IVIG
      in the treatment of cholangitis.

PMID- 29468409
TI  - Performance of Arsi-Bale sheep fed urea treated maize cob as basal diet and
      supplemented with graded levels of concentrate mixture.
AB  - The experiment was conducted using 20 yearling intact male Arsi-Bale sheep with a
      mean body weight of 20.56 +/- 0.45 (mean +/- SD) to investigate the performance
      and economic benefit of graded levels of concentrate supplementation to urea
      treated maize cob (UTMC)-based diet. The experiment consisted of 7 days of
      digestibility trial and subsequent 90 days of feeding trial. Before the
      commencement of the experiment, sheep were vaccinated against common infectious
      diseases, dewormed, and disinfected against internal and external parasites,
      respectively. The experimental design was randomized complete block design. The
      sheep were grouped into five blocks of four animals based on their initial body
      weight, and one animal from each block was randomly assigned to one of the four
      treatments. The treatments included ad libitum feeding of UTMC (T1) and
      supplementation with a concentrate mixture composed of wheat bran (WB) and noug
      seed cake (NSC) in 2:1 ratio, which were offered at 150 g (T2), 250 g (T3), and
      350 g (T4) DM/head/day. The CP content of the UTMC was 9.3% on DM basis. The
      daily DM intake of UTMC was higher (P < 0.001) for T4 (614.6 g) compared to T1
      (505.1 g), T2 (538.9 g), and T3 (590.3 g). Total DM intake was higher (P < 0.001)
      for supplemented treatments T2 (688.4 g), T3 (844.1 g), and T4 (966.9 g).
      Supplementation did not improve (P > 0.05) digestibility of DM, OM, NDF, and ADF,
      except CP digestibility which was significant (P < 0.001) across treatments.
      Supplementation increased (P < 0.001) final body weight (FBWT), feed conversion
      efficiency (FCE), and average daily weight gain (ADG). The average daily gain
      (ADG) was highest (P < 0.001) in T4 (80.8 +/- 7.74 g/day) followed by T3 (33.3 +/
      7.74 g/day) and T2 (23.1 +/- 0.95 kg) whereas the un-supplemented animals lost
      about 9.2 g/day. The highest total return, net income, and marginal rate of
      return were observed in higher level supplemented sheep than the control.
      Therefore, T4 improved biological performance and marginal rate of return than
      the other treatments and can be considered as better alternative feed supplement
      in UTMC-based feeding of Arsi-Bale sheep in Ethiopia.

PMID- 29468410
TI  - Nasogastric tube location: a diagnostic dilemma.

PMID- 29468411
TI  - Differentiating muscle relaxant syringes to reduce syringe swap error.

PMID- 29468412
TI  - Fuzzy Expert System based on a Novel Hybrid Stem Cell (HSC) Algorithm for
      Classification of Micro Array Data.
AB  - In the growing scenario, microarray data is extensively used since it provides a
      more comprehensive understanding of genetic variants among diseases. As the gene
      expression samples have high dimensionality it becomes tedious to analyze the
      samples manually. Hence an automated system is needed to analyze these samples.
      The fuzzy expert system offers a clear classification when compared to the
      machine learning and statistical methodologies. In fuzzy classification,
      knowledge acquisition would be a major concern. Despite several existing
      approaches for knowledge acquisition much effort is necessary to enhance the
      learning process. This paper proposes an innovative Hybrid Stem Cell (HSC)
      algorithm that utilizes Ant Colony optimization and Stem Cell algorithm for
      designing fuzzy classification system to extract the informative rules to form
      the membership functions from the microarray dataset. The HSC algorithm uses a
      novel Adaptive Stem Cell Optimization (ASCO) to improve the points of membership
      function and Ant Colony Optimization to produce the near optimum rule set. In
      order to extract the most informative genes from the large microarray dataset a
      method called Mutual Information is used. The performance results of the proposed
      technique evaluated using the five microarray datasets are simulated. These
      results prove that the proposed Hybrid Stem Cell (HSC) algorithm produces a
      precise fuzzy system than the existing methodologies.

PMID- 29468413
TI  - The level of DNA damage in mouse hematopoietic cells and in frog and human blood
      cells, as induced by the action of reactive oxygen species in vitro.
AB  - Comparative studies of the level of DNA damage induced in vitro by X-rays (0-8
      Gy) or hydrogen peroxide (0-300 uM) in cells of blood, spleen, and bone marrow of
      mice and in blood cells of frogs and humans were performed using the alkaline
      comet assay. For both agents, the levels of induced DNA damage in
      leucocytes/splenocytes of mice were higher than those in blood cells of frogs and
      humans, while in human leucocytes, they were comparable with those in frog blood
      cells. The rate of DNA repair in frog blood cells was very slow. The results
      suggest that the levels of radiation-induced DNA damage are not in accordance
      with species radiosensitivity (according to LD50/30) but rather with the
      intrinsic peculiarities of cells.

PMID- 29468414
TI  - [Severe caffeine poisoning with rhabdomyolysis].
AB  - We report the case of a young man who took a large amount of caffeine powder
      dissolved in water in a suicide attempt. He was found comatose. The initial
      diagnosis was difficult. In hospital he suffered from rhabdomyolysis with renal
      failure and sepsis rapidly developed. After renal replacement treatment with
      hemodialysis, long-term artificial ventilation with tracheotomy and a 3-week stay
      in the intensive care unit, the patient could be discharged to a rehabilitation
      center.

PMID- 29468415
TI  - The ileal FGF15/19 to hepatic FGFR4 axis regulates liver regeneration after
      partial hepatectomy in mice.
AB  - Fibroblast growth factor (FGF) has been considered to modulate liver regeneration
      (LR) after partial hepatectomy (PH) at the tissue level. Previous studies have
      demonstrated that FGF15 and FGF19 induce the activation of its receptor, FGF
      receptor 4 (FGFR4), which can promote hepatocellular carcinoma progression and
      regulate liver lipid metabolism. In this study, we aimed to explore the role of
      the ileal FGF15/19- hepatic FGFR4 axis in the LR after PH. Male C57BL/6 mice aged
      8-12 weeks were partially hepatectomized and assessed for expression of ileal
      FGF15/19 to hepatic FGFR4 signaling. We used recombinant human FGF19 protein and
      a small interfering RNA (siRNA) of FGFR4 to regulate expression of the FGF15/19
      FGFR4 axis in vitro and in vivo. The proliferation and cell cycle of hepatocytes,
      the expression levels of FGF15/19-FGFR4 downstream molecules, liver recovery, and
      lipid metabolism were assessed. We found that both ileal and serum FGF15
      expression were upregulated and hepatic FGFR4 was activated after PH in mice.
      FGF15/19 promoted cell cycle progression, enhanced proliferation, and reduced
      hepatic lipid accumulation of hepatocytes both in vitro and in vivo. Furthermore,
      the proliferative effect and lipid regulatory properties of FGF15/19 were
      dependent on FGFR4 in hepatocytes. In addition, ileal FGF15/19-hepatic FGFR4
      transduction during hepatocyte proliferation was regulated by extracellular
      regulated protein kinase (ERK) 1/2. In conclusion, the ileal FGF15/19 to hepatic
      FGFR4 axis is activated and promotes LR after PH in mice, supporting the
      potential of ileal FGF15/19 to hepatic FGFR4 axis-targeted therapy to enhance LR
      after PH.

PMID- 29468416
TI  - Motivational sensitivity of outcome-response priming: Experimental research and
      theoretical models.
AB  - Outcome-response (O-R) priming is at the core of various associative theories of
      human intentional action. This is a simple and parsimonious mechanism by which
      activation of outcome representations (e.g. thinking about the light coming on)
      leads to activation of the associated motor patterns required to achieve it (e.g.
      pushing the light switch). In the current manuscript, we review the evidence for
      such O-R associative links demonstrated by converging (yet until now, separate)
      strands of research. While there is a wealth of evidence that both the perceptual
      and motivational properties of an outcome can be encoded in the O-R association
      and mediate O-R priming, we critically examine the integration of these
      mechanisms and the conditions under which motivational factors constrain the
      sensory O-R priming effect. We discuss the clinical relevance of this O-R priming
      mechanism, whether it can satisfactorily account for human goal-directed
      behaviour, and the implications for theories of human action control.

PMID- 29468417
TI  - Eliciting the experiences of the adolescent-parent dyad following critical care
      admission: a pilot study.
AB  - : Critically ill adolescents are usually treated on intensive care units
      optimised for much older adults or younger children. The way they access and
      experience health services may be very different to most adolescent service
      users, and existing quality criteria may not apply to them. The objectives of
      this pilot study were, firstly, to determine whether adolescents and their
      families were able to articulate their experiences of their critical care
      admission and secondly, to identify the factors that are important to them during
      their intensive care unit (ICU) or high dependency unit (HDU) stay. Participants
      were 14-17 year olds who had previously had an emergency admission to an adult or
      paediatric ICU/HDU in one of four UK hospitals (two adult, two paediatric) and
      their parents. Semi-structured interviews were conducted with eight mother
      adolescent dyads and one mother. Interviews were transcribed and analysed using
      framework analysis. CONCLUSION: The main reported determinant of high-quality
      care was the quality of interaction with staff. The significance of these
      interactions and their environment depended on adolescents' awareness of their
      surroundings, which was often limited in ICU and changed significantly over the
      course of their illness. Qualitative interview methodology would be difficult to
      scale up for this group. What is known * Critically ill adolescents are usually
      treated on intensive care units optimised for older adults or younger children. *
      The way they access and experience health services may be different to most
      adolescent patients; existing quality criteria may not apply. What is new *
      Reported determinants of high-quality care were age-appropriateness of the
      environment, respectfulness and friendliness of staff, communication and
      inclusion in healthcare decisions. * The significance of these depended on
      adolescents' awareness of their surroundings, which was often limited and changed
      over the course of their illness.

PMID- 29468418
TI  - Matrix Optical Absorption in UV-MALDI MS.
AB  - In ultraviolet matrix-assisted laser desorption/ionization mass spectrometry (UV
      MALDI MS) matrix compound optical absorption governs the uptake of laser energy,
      which in turn has a strong influence on experimental results. Despite this,
      quantitative absorption measurements are lacking for most matrix compounds.
      Furthermore, despite the use of UV-MALDI MS to detect a vast range of compounds,
      investigations into the effects of laser energy have been primarily restricted to
      single classes of analytes. We report the absolute solid state absorption spectra
      of the matrix compounds alpha-cyano-4-hydroxycinnamic acid (CHCA), para
      nitroaniline (PNA), 2-mercaptobenzothiazole (MBT), 2,5-dihydroxybenzoic acid (2,5
      DHB), and 2,4,6-trihydroxyacetophenone (THAP). The desorption/ionization
      characteristics of these matrix compounds with respect to laser fluence was
      investigated using mixed systems of matrix with either angiotensin II, PC(34:1)
      lipid standard, or haloperidol, acting as representatives for typical classes of
      analyte encountered in UV-MALDI MS. The first absolute solid phase spectra for
      PNA, MBT, and THAP are reported; additionally, inconsistencies between previously
      published spectra for CHCA are resolved. In light of these findings, suggestions
      are made for experimental optimization with regards to matrix and laser
      wavelength selection. The relationship between matrix optical cross-section and
      wavelength-dependant threshold fluence, fluence of maximum ion yield, and R, a
      new descriptor for the change in ion intensity with fluence, are described. A
      matrix cross-section of 1.3 * 10-17 cm-2 was identified as a potential minimum
      for desorption/ionization of analytes. Graphical Abstract ?.

PMID- 29468419
TI  - Establishment of an Italian chronic migraine database: a multicenter pilot study.
AB  - To optimize chronic migraine (CM) ascertainment and phenotype definition, provide
      adequate clinical management and health care procedures, and rationalize economic
      resources allocation, we performed an exploratory multicenter pilot study aimed
      at establishing a CM database, the first step for developing a future Italian CM
      registry. We enrolled 63 consecutive CM patients in four tertiary headache
      centers screened with face-to-face interviews using an ad hoc dedicated semi
      structured questionnaire gathering detailed information on life-style, behavioral
      and socio-demographic factors, comorbidities, and migraine features before and
      after chronicization and healthcare resource use. Our pilot study provided useful
      insights revealing that CM patients (1) presented in most cases symptoms of
      peripheral trigeminal sensitization, a relatively unexpected feature which could
      be useful to unravel different CM endophenotypes and to predict trigeminal
      targeted treatments' responsiveness; (2) had been frequently admitted to
      emergency departments; (3) had undergone, sometime repeatedly, unnecessary or
      inappropriate investigations; (4) got rarely illness benefit exemption or
      disability allowance only. We deem that the expansion of the database-shortly
      including many other Italian headache centers-will contribute to more precisely
      outline CM endophenotypes, hence improving management, treatment, and economic
      resource allocation, ultimately reducing CM burden on both patients and health
      system.

PMID- 29468420
TI  - Temperature-Induced Surface Effects on Drug Nanosuspensions.
AB  - PURPOSE: The trial-and-error approach is still predominantly used in
      pharmaceutical development of nanosuspensions. Physicochemical dispersion
      stability is a primary focus and therefore, various analytical bulk methods are
      commonly employed. Clearly less attention is directed to surface changes of
      nanoparticles even though such interface effects can be of pharmaceutical
      relevance. Such potential effects in drug nanosuspensions were to be studied for
      temperatures of 25 and 37 degrees C by using complementary surface analytical
      methods. METHODS: Atomic force microscopy, inverse gas chromatography and UV
      surface dissolution imaging were used together for the first time to assess
      pharmaceutical nanosuspensions that were obtained by wet milling. Fenofibrate and
      bezafibrate were selected as model drugs in presence of sodium dodecyl sulfate
      and hydroxypropyl cellulose as anionic and steric stabilizer, respectively.
      RESULTS: It was demonstrated that in case of bezafibrate nanosuspension, a
      surface modification occurred at 37 degrees C compared to 25 degrees C, which
      notably affected dissolution rate. By contrast, no similar effect was observed in
      case of fenofibrate nanoparticles. CONCLUSIONS: The combined usage of analytical
      surface methods provides the basis for a better understanding of phenomena that
      take place on drug surfaces. Such understanding is of importance for
      pharmaceutical development to achieve desirable quality attributes of
      nanosuspensions.

PMID- 29468422
TI  - Molecular profiling and comprehensive genome-wide analysis of somatic copy number
      alterations in gastric intramucosal neoplasias based on microsatellite status.
AB  - BACKGROUND: We attempted to identify the molecular profiles of gastric
      intramucosal neoplasia (IMN; low-grade dysplasia, LGD; high-grade dysplasia, HGD;
      intramucosal cancer, IMC) by assessing somatic copy number alterations (SCNAs)
      stratified by microsatellite status (microsatellite stable, MSS; microsatellite
      instable, MSI). Thus, microsatellite status was determined in 84 tumors with MSS
      status and 16 tumors with MSI status. METHODS: One hundred differentiated type
      IMNs were examined using SCNAs. In addition, genetic mutations (KRAS, BRAF,
      PIK3CA, and TP53) and DNA methylation status (low, intermediate and high) were
      also analyzed. Finally, we attempted to identify molecular profiles using a
      hierarchical clustering analysis. RESULTS: Three patterns could be categorized
      according to SCNAs in IMNs with the MSS phenotype: subgroups 1 and 2 showing a
      high frequency of SCNAs, and subgroup 3 displaying a low frequency of SCNAs
      (subgroup 1 > 2 > 3 for SCNA). Subgroup 1 could be distinguished from subgroup 2
      by the numbers of total SCNAs (gains and losses) and SCN gains (subgroup 1 > 2).
      The SCNA pattern of LGD was different from that of HGD and IMC. Moreover, IMNs
      with the MSI phenotype could be categorized into two subtypes: high frequency of
      SCNAs and low frequency of SCNAs. Genetic mutations and DNA methylation status
      did not differ among subgroups in IMNs. CONCLUSION: Molecular profiles stratified
      by SCNAs based on microsatellite status may be useful for elucidation of the
      mechanisms of early gastric carcinogenesis.

PMID- 29468423
TI  - A novel method for studying airway hyperresponsiveness in allergic guinea pigs in
      vivo using the PreciseInhale system for delivery of dry powder aerosols.
AB  - Inhaled adenosine receptor agonists induce bronchoconstriction and inflammation
      in asthma and are used as bronchial challenge agents for the diagnosis of asthma
      and in respiratory drug development. Recently developed dry powder aerosols of
      adenosine have several advantages over nebulised adenosine 5'-monophosphate (AMP)
      as bronchial challenge agents. However, reverse translation of this bronchial
      challenge technique to pre-clinical drug development is limited by the difficulty
      of administering powder aerosols to animals. The aim of the current study was to
      develop methods for delivering powder aerosols of adenosine receptor agonists to
      sensitised guinea pigs (as a model of allergic asthma) and evaluate their effect
      as challenge agents for the measurement of airway responsiveness. The
      PreciseInhale system delivered micronised AMP and adenosine powders, with mass
      median aerodynamic diameters of 1.81 and 3.21 MUm and deposition fractions of 31
      and 48% in the lungs, respectively. Bronchoconstrictor responses in passively
      sensitised, anaesthetised, spontaneously breathing guinea pigs were compared to
      responses to nebulised and intravenously administered AMP and adenosine. AMP- and
      adenosine-induced bronchoconstriction following all routes of administration with
      the magnitude of response ranking intravenous > dry powder > nebulisation,
      probably reflecting differences in exposure to the adenosine agonists delivered
      by the different routes. In conclusion, the PreciseInhale system delivered AMP
      and adenosine dry powder aerosols accurately into the lungs, suggesting this
      method can be used to investigate drug effects on airway responsiveness.

PMID- 29468424
TI  - Full depth measurement of tenofovir transport in rectal mucosa using confocal
      Raman spectroscopy and optical coherence tomography.
AB  - The prophylactic activity of antiretroviral drugs applied as microbicides against
      sexually transmitted HIV is dependent upon their concentrations in infectable
      host cells. Within mucosal sites of infection (e.g., vaginal and rectal mucosa),
      those cells exist primarily in the stromal layer of the tissue. Traditional
      pharmacokinetic studies of these drugs have been challenged by poor temporal and
      spatial specificity. Newer techniques to measure drug concentrations, involving
      Raman spectroscopy, have been limited by laser penetration depth into tissue.
      Utilizing confocal Raman spectroscopy (RS) in conjunction with optical coherence
      tomography (OCT), a new lateral imaging assay enabled concentration distributions
      to be imaged with spatial and temporal specificity throughout the full depth of a
      tissue specimen. The new methodology was applied in rectal tissue using a
      clinical rectal gel formulation of 1% tenofovir (TFV). Confocal RS revealed
      diffusion-like behavior of TFV through the tissue specimen, with significant
      partitioning of the drug at the interface between the stromal and adipose tissue
      layers. This has implications for drug delivery to infectable tissue sites. The
      new assay can be applied to rigorously analyze microbicide transport and
      delineate fundamental transport parameters of the drugs (released from a variety
      of delivery vehicles) throughout the mucosa, thus informing microbicide product
      design.

PMID- 29468425
TI  - Sediment matrix characterization as a tool for evaluating the environmental
      impact of heavy metals in metal mining, smelting, and ore processing areas.
AB  - In this work, the matrix characterization (mineralogy, total and local chemical
      composition, and total organic (TOC) and inorganic carbon (TIC) contents) of
      different types of sediments from mining- and metallurgy-influenced areas and the
      assessment of the impact of the matrix on the association of potentially
      hazardous metals with the mineral phases of these samples, which affect their
      mobility in the environment, are presented. For these purposes, sediment samples
      with different origins and from different locations in the environment were
      analyzed. Anthropogenic sediments from metal-rich post-flotation tailings
      (Lintich, Slovakia) represent waste from ore processing, natural river sediments
      from the Hornad River (Kosice, Slovakia) represent areas influenced predominantly
      by the metallurgical industry, and lake sediments from a water reservoir Ruzin
      (inflow from the Hornad and Hnilec Rivers, Slovakia) represent the impact of the
      metallurgical and/or mining industries. The total metal contents were determined
      by X-ray fluorescence (XRF) analysis, the local chemical and morphological
      microanalysis by scanning electron microscopy with energy-dispersive spectroscopy
      (SEM-EDS), and the TOC and TIC contents by infrared (IR) spectrometry. The
      mobility/bioavailability of Cu, Pb, and Zn in/from sediments at the studied areas
      was assessed by ethylenediaminetetraacetic acid (EDTA) and acetic acid (AA)
      extraction and is discussed in the context of the matrix composition. The
      contents of selected potentially hazardous elements in the extracts were
      determined by the high-resolution continuum source flame atomic absorption
      spectrometry (HR-CS FAAS).

PMID- 29468426
TI  - EPR spectroscopy of complex biological iron-sulfur systems.
AB  - From the very first discovery of biological iron-sulfur clusters with EPR, the
      spectroscopy has been used to study not only purified proteins but also complex
      systems such as respiratory complexes, membrane particles and, later, whole
      cells. In recent times, the emphasis of iron-sulfur biochemistry has moved from
      characterization of individual proteins to the systems biology of iron-sulfur
      biosynthesis, regulation, degradation, and implications for human health.
      Although this move would suggest a blossoming of System-EPR as a specific, non
      invasive monitor of Fe/S (dys)homeostasis in whole cells, a review of the
      literature reveals limited success possibly due to technical difficulties in
      adherence to EPR spectroscopic and biochemical standards. In an attempt to boost
      application of System-EPR the required boundary conditions and their practical
      applications are explicitly and comprehensively formulated.

PMID- 29468427
TI  - Maximizing gain in high-throughput screening using conformal prediction.
AB  - Iterative screening has emerged as a promising approach to increase the
      efficiency of screening campaigns compared to traditional high throughput
      approaches. By learning from a subset of the compound library, inferences on what
      compounds to screen next can be made by predictive models, resulting in more
      efficient screening. One way to evaluate screening is to consider the cost of
      screening compared to the gain associated with finding an active compound. In
      this work, we introduce a conformal predictor coupled with a gain-cost function
      with the aim to maximise gain in iterative screening. Using this setup we were
      able to show that by evaluating the predictions on the training data, very
      accurate predictions on what settings will produce the highest gain on the test
      data can be made. We evaluate the approach on 12 bioactivity datasets from
      PubChem training the models using 20% of the data. Depending on the settings of
      the gain-cost function, the settings generating the maximum gain were accurately
      identified in 8-10 out of the 12 datasets. Broadly, our approach can predict what
      strategy generates the highest gain based on the results of the cost-gain
      evaluation: to screen the compounds predicted to be active, to screen all the
      remaining data, or not to screen any additional compounds. When the algorithm
      indicates that the predicted active compounds should be screened, our approach
      also indicates what confidence level to apply in order to maximize gain. Hence,
      our approach facilitates decision-making and allocation of the resources where
      they deliver the most value by indicating in advance the likely outcome of a
      screening campaign.

PMID- 29468428
TI  - The production, properties, and applications of thermostable steryl glucosidases.
AB  - Extremophilic microorganisms are a rich source of enzymes, the enzymes which can
      serve as industrial catalysts that can withstand harsh processing conditions. An
      example is thermostable beta-glucosidases that are addressing a challenging
      problem in the biodiesel industry: removing steryl glucosides (SGs) from
      biodiesel. Steryl glucosidases (SGases) must be tolerant to heat and solvents in
      order to function efficiently in biodiesel. The amphipathic nature of SGs also
      requires enzymes with an affinity for water/solvent interfaces in order to
      achieve efficient hydrolysis. Additionally, the development of an enzymatic
      process involving a commodity such as soybean biodiesel must be cost-effective,
      necessitating an efficient manufacturing process for SGases. This review
      summarizes the identification of microbial SGases and their applications,
      discusses biodiesel refining processes and the development of analytical methods
      for identifying and quantifying SGs in foods and biodiesel, and considers
      technologies for strain engineering and process optimization for the heterologous
      production of a SGase from Thermococcus litoralis. All of these technologies
      might be used for the production of other thermostable enzymes. Structural
      features of SGases and the feasibility of protein engineering for novel
      applications are explored.

PMID- 29468429
TI  - Comparative genomic analysis of the Lipase3 gene family in five plant species
      reveals distinct evolutionary origins.
AB  - Lipases are physiologically important and ubiquitous enzymes that share a
      conserved domain and are classified into eight different families based on their
      amino acid sequences and fundamental biological properties. The Lipase3 family of
      lipases was reported to possess a canonical fold typical of alpha/beta hydrolases
      and a typical catalytic triad, suggesting a distinct evolutionary origin for this
      family. Genes in the Lipase3 family do not have the same functions, but maintain
      the conserved Lipase3 domain. There have been extensive studies of Lipase3
      structures and functions, but little is known about their evolutionary histories.
      In this study, all lipases within five plant species were identified, and their
      phylogenetic relationships and genetic properties were analyzed and used to group
      them into distinct evolutionary families. Each identified lipase family contained
      at least one dicot and monocot Lipase3 protein, indicating that the gene family
      was established before the split of dicots and monocots. Similar intron/exon
      numbers and predicted protein sequence lengths were found within individual
      groups. Twenty-four tandem Lipase3 gene duplications were identified, implying
      that the distinctive function of Lipase3 genes appears to be a consequence of
      translocation and neofunctionalization after gene duplication. The functional
      genes EDS1, PAD4, and SAG101 that are reportedly involved in pathogen response
      were all located in the same group. The nucleotide diversity (Dxy) and the ratio
      of nonsynonymous to synonymous nucleotide substitutions rates (Ka/Ks) of the
      three genes were significantly greater than the average across the genomes. We
      further observed evidence for selection maintaining diversity on three genes in
      the Toll-Interleukin-1 receptor type of nucleotide binding/leucine-rich repeat
      immune receptor (TIR-NBS LRR) immunity-response signaling pathway, indicating
      that they could be vulnerable to pathogen effectors.

PMID- 29468430
TI  - Impaired aspirin-mediated platelet function inhibition in resuscitated patients
      with acute myocardial infarction treated with therapeutic hypothermia: a
      prospective, observational, non-randomized single-centre study.
AB  - The majority of resuscitated patients present with underlying cardiac disease,
      and out of these myocardial infarction is most common. Immediate interventional
      treatment is recommended and routinely requires dual antiplatelet therapy
      including aspirin and a P2Y12-inhibitor. Therapeutic hypothermia or target
      temperature management is also recommended in these patients. Cardiogenic shock
      as well as reduced body temperature impacts platelet reactivity and its medical
      inhibition. The study aims to quantify aspirin- and P2Y12-mediated platelet
      inhibition in patients presenting with myocardial infarction and cardiopulmonary
      resuscitation. Twenty-five resuscitated patients were enrolled in this
      prospective, observational, non-randomized single-centre study. These patients
      were compared to 77 matched controls from the ATLANTIS-ACS database of non
      resuscitated patients with myocardial infarction. Platelet function testing was
      performed by light transmittance aggregometry. Aspirin reactivity was monitored
      by inducing platelet aggregation with collagen and arachidonic acid,
      respectively. P2Y12 inhibition was recorded by stimulation of platelet
      aggregation with adenosine diphosphate. To quantify the overall platelet
      response, thrombin receptor-activated peptide was used. Aspirin-mediated platelet
      reactivity decreased significantly in resuscitated patients during the first days
      and was significantly weaker on day 3 (collagen AUC 253.8 (122.7-352.2) vs. 109.0
      (73.0-182.0); p = 0.022). P2Y12-mediated platelet inhibition was also impaired in
      resuscitated patients on day 3 (mean ADP AUC (IQR): CPR 172.1 (46.7-346.5) vs.
      control 43.9 (18.9-115.2); p < 0.05). Aspirin- and P2Y12-mediated platelet
      inhibition is impaired in resuscitated patients treated with therapeutic
      hypothermia. On day 3, we recorded lowest inhibitory effects of both drug types
      and patients might be at particular risk at that time. Potentially, intravenous
      aspirin and P2Y12 inhibitors might still supply a more predictable and stable
      platelet inhibition.

PMID- 29468431
TI  - Synthesis of molecular imprinting polymers for extraction of gallic acid from
      urine.
AB  - The molecularly imprinted polymers for gallic acid were synthesized by
      precipitation polymerization. During the process of synthesis a non-covalent
      approach was used for the interaction of template and monomer. In the
      polymerization process, gallic acid was used as a template, acrylic acid as a
      functional monomer, ethylene glycol dimethacrylate as a cross-linker and 2,2'
      azobisisobutyronitrile as an initiator and acetonitrile as a solvent. The
      synthesized imprinted and non-imprinted polymer particles were characterized by
      using Fourier-transform infrared spectroscopy and scanning electron microscopy.
      The rebinding efficiency of synthesized polymer particles was evaluated by batch
      binding assay. The highly selective imprinted polymer for gallic acid was MIPI1
      with a composition (molar ratio) of 1:4:20, template: monomer: cross-linker,
      respectively. The MIPI1 showed highest binding efficiency (79.50%) as compared to
      other imprinted and non-imprinted polymers. The highly selective imprinted
      polymers have successfully extracted about 80% of gallic acid from spiked urine
      sample.

PMID- 29468432
TI  - Seed (Sperma) and Kuema in Aristotle's Generation of Animals.
AB  - There are two different notions of seed (sperma) at work in the Generation of
      Animals: seed as the spermatic residue (perittoma), which concerns only the male
      and the female generative contributions, and seed as the kuema and first mixture
      of the two generative contributions. The latter is a notion of seed common to
      plants and animals. The passage in GA I.18, 724b12-22 where Aristotle
      distinguishes between these two notions of seed has been mistakenly discredited
      as inauthentic or simply as irrelevant for understanding the seeds of animals. On
      the other hand, recent studies have rather focused on the seed as spermatic
      residue (in particular, the female contribution as seed), paying little attention
      to the notion of seed as kuema. In this paper I defend the authenticity and
      relevance of this passage and show how understanding the notion of seed as kuema
      is essential to have a complete picture of Aristotle's account of seed. This
      common notion of seed makes sense of Aristotle's otherwise puzzling use of the
      word "sperma" to designate the seeds of plants, the kuema, the fertilized eggs,
      and the first mixture of the two generative contributions. It also proves helpful
      in determining what the word 'sperma' stands for in key passages, such as Metaph.
      IX.7.

PMID- 29468433
TI  - Merging perspectives: genotype-directed molecular therapy for hereditary diffuse
      gastric cancer (HDGC) and E-cadherin-EGFR crosstalk.
AB  - Hereditary diffuse gastric cancer is a cancer predisposition syndrome associated
      with germline mutations of the E-cadherin gene (CDH1; NM_004360). Male CDH1
      germline mutation carriers have by the age of 80 years an estimated 70%
      cumulative incidence of gastric cancer, females of 56% for gastric and of 42% for
      lobular breast cancer. Metastatic HDGC has a poor prognosis which is worse than
      for sporadic gastric cancer. To date, there have been no treatment options
      described tailored to this molecular subtype of gastric cancer. Here we review
      recent differential drug screening and gene expression results in c.1380del CDH1
      mutant HDGC cells which identified drug classes targeting PI3K (phosphoinositide
      3-kinase), MEK (mitogen-activated protein kinase), FAK (focal adhesion kinase),
      PKC (protein kinase C), and TOPO2 (topoisomerase II) as selectively more
      effective in cells with defective CDH1 function. ERK1-ERK2 (extracellular signal
      regulated kinase) signaling measured as top enriched network in c.1380delA CDH1
      mutant cells. We compared these findings to synthetic lethality and
      pharmacological screening results in isogenic CDH1-/- MCF10A mammary epithelial
      cells with and without CDH1 expression and current knowledge of E
      cadherin/catenin-EGFR cross-talk, and suggest different rationales how loss of E
      cadherin function activates PI3K, mTOR, EGFR, or FAK signaling. These leads
      represent molecularly selected treatment options tailored to the treatment of
      CDH1-deficient familial gastric cancer.

PMID- 29468434
TI  - Preservation of the nipple-areola complex in skin-sparing mastectomy for early
      breast cancer.
AB  - PURPOSE: Skin-sparing mastectomy (SSM) enables a radical cure of breast cancer
      while overcoming the cosmetic issues related to surgery. We review our experience
      of performing SSMs and assess whether preservation of the nipple-areola complex
      (NAC) could have been an option for some patients who underwent SSM. METHODS: The
      subjects of this retrospective study were women who underwent SSM that utilized
      four incision types; namely, the so-called tennis racket incision, a periareolar
      and midaxillary incision, an areola-sparing and midaxillary incision, and a small
      transverse elliptical incision. We assessed whether preservation of the NAC would
      have been an option in SSM, based on histologic examination of three serial cut
      surfaces of the specimen around the nipple, ruling out the option when evidence
      of the malignant lesion/s was found in at least one of the following locations:
      in the nipple, within a 1-cm radius from the base of the nipple, or within 1 cm
      from the surface of the NAC. RESULTS: We performed 193 SSMs. The cumulative 10
      year local disease-free survival rate was 98%, with 89% of patients reporting
      levels of satisfaction with the reconstructed breast, of excellent, very good, or
      good. We evaluated that 70 of the 193 procedures could have been performed as
      nipple-sparing mastectomy (NSM). CONCLUSIONS: The outcomes of SSM in this series
      were excellent and NSM might have been an option for about one-third of the
      patients.

PMID- 29468435
TI  - Additional lymph node dissection for primary colorectal cancer invading another
      colon region.
AB  - PURPOSE: Surgery remains the curative treatment of choice for colorectal cancer
      (CRC). However, to our knowledge, no report has addressed the usefulness of
      additional regional lymph node dissection for primary CRC that has invaded
      another colon region. METHODS: We reviewed the clinicopathological
      characteristics and outcomes of eight patients who underwent surgery between
      March, 2005 and August, 2014, for CRC that invaded another region of the colon.
      RESULTS: Five patients underwent additional regional lymph node dissection in the
      area of the invaded colon and one patient had lymph node metastasis in the
      region. Two of three patients who did not undergo additional regional lymph node
      dissection were found to have regional lymph node recurrences in the area during
      the follow-up period. Although there was no statistical correlation between extra
      regional lymph node metastasis and clinicopathological or operative factors, the
      patients with extra-regional lymph node metastasis or recurrence had primary
      regional lymph node metastasis. CONCLUSION: For curative intent, surgeons may
      need to perform additional regional lymph node dissection for primary CRC
      invading another colon region.

PMID- 29468436
TI  - Repair of infected mitral valves: what have we learned?
AB  - Infective endocarditis (IE) is associated with high mortality and morbidity and
      requires surgical intervention in about half of all patients. Mitral valve repair
      (MVrep) is reported to achieve better results than mitral valve replacement
      because the insertion of a prosthesis during active infection is avoided.
      However, MVrep in active IE is complicated and no definitive guidelines have been
      compiled. The current study reviews the literature from 2000 to 2016 and
      summarizes the surgical details of MVrep for IE.

PMID- 29468437
TI  - Young adults diagnosed with Hodgkin lymphoma are at risk of relapsing late: a
      comprehensive analysis of late relapse in Hodgkin lymphoma.
AB  - PURPOSE: Majority of relapses in Hodgkin lymphoma (HL) occur within 3 years after
      initial treatment, late relapses (LR), happening 5 or more years after first
      diagnosis is rare events. Neither clinical characteristics, risk factors, nor
      optimal treatment is well described for LR patients. Our aim was to provide a
      comprehensive analysis on the LR of HL to outline a patient population at risk of
      relapsing late. PATIENTS AND METHODS: 637 HL patients were treated at the
      University of Debrecen between 1981 and 2010. Patient data was evaluated
      retrospectively. Survival analysis was performed using the Kaplan-Meier method
      and odds ratios (OR) were identified by binary logistic regression models.
      RESULTS: With a median observational time of 9.08 years 584 (91%) HL patients
      achieved complete remission (CR) after first line treatment. Relapse occurred in
      176 (28%) patients, 26 (4%) of them 5 or more years after first diagnosis. With
      multivariable analysis, initial diagnosis before the age of 24 (p < 0.001),
      initial presentation between 1981 and 1990 or 1991-2000 (p = 0.025 and p = 0.023,
      respectively) and first line treatment with radiotherapy only (p = 0.034) were
      identified as independent risk factors for LR. We observed a significantly
      impaired OS for patients with early relapse HL compared to those in long-term
      remission or experiencing LR (p < 0.001). CONCLUSION: Late relapse of HL presents
      with clinical characteristics very similar to primary disease and appears to have
      a good prognosis. First diagnosis in childhood or young adulthood and first line
      treatment before the ABVD era increases the risk of relapsing late.

PMID- 29468439
TI  - Theoretical investigation of the use of nanocages with an adsorbed halogen atom
      as anode materials in metal-ion batteries.
AB  - The applicability of C44, B22N22, Ge44, and Al22P22 nanocages, as well as
      variants of those nanocages with an adsorbed halogen atom, as high-performance
      anode materials in Li-ion, Na-ion, and K-ion batteries was investigated
      theoretically via density functional theory. The results obtained indicate that,
      among the nanocages with no adsorbed halogen atom, Al22P22 would be the best
      candidate for a novel anode material for use in metal-ion batteries. Calculations
      also suggest that K-ion batteries which utilize these nanocages as anode
      materials would give better performance and would yield higher cell voltages than
      the corresponding Li-ion and Na-ion batteries with nanocage-based anodes. Also,
      the results for the nanocages with an adsorbed halogen atom imply that employing
      them as anode materials would lead to higher cell voltages and better metal-ion
      battery performance than if the nanocages with no adsorbed halogen atom were to
      be used as anode materials instead. Results further implied that nanocages with
      an adsorbed F atom would give higher cell voltages and better battery performance
      than nanocages with an adsorbed Cl or Br atom. We were ultimately able to
      conclude that a K-ion battery that utilized Al21P22 with an adsorbed F atom as
      its anode material would afford the best metal-ion battery performance; we
      therefore propose this as a novel highly efficient metal-ion battery. Graphical
      abstract The results of a theoretical investigation indicated that Al22P22 is a
      better candidate for a high-performance anode material in metal-ion batteries
      than Ge44 is. Calculations also showed that K-ion batteries with nanocage-based
      anodes would produce higher cell voltages and perform better than the equivalent
      Li-ion and Na-ion batteries with nanocage-based anodes, and that anodes based on
      nanocages with an adsorbed F atom would perform better than anodes based on
      nanocages with an adsorbed Cl or Br atom.

PMID- 29468438
TI  - Durable treatment-free remission in patients with chronic myeloid leukemia in
      chronic phase following frontline nilotinib: 96-week update of the ENESTfreedom
      study.
AB  - PURPOSE: ENESTfreedom is evaluating treatment-free remission (TFR) following
      frontline nilotinib in patients with chronic myeloid leukemia (CML) in chronic
      phase. Following our primary analysis at 48 weeks, we here provide an updated 96
      week analysis. METHODS: Attempting TFR required >= 3 years of nilotinib, a
      molecular response of MR4.5 [BCR-ABL1 <= 0.0032% on the International Scale (BCR
      ABL1IS)], and sustained deep molecular response (DMR) during a 1-year
      consolidation phase. Patients restarted nilotinib following loss of major
      molecular response (MMR; BCR-ABL1IS <= 0.1%). RESULTS: Ninety-six weeks after
      stopping treatment (3.6-year median prior nilotinib duration), 93 of 190 patients
      (48.9%) remained in TFR. Of 88 patients who restarted nilotinib following loss of
      MMR, 87 regained MMR and 81 regained MR4.5 by the data cut-off. Ninety-six-week
      TFR rates were 61.3, 50.0, and 28.6% in patients with low, intermediate, and high
      Sokal risk scores at diagnosis, respectively. Patients consistently in MR4.5
      during consolidation had higher TFR rates (50.6%) than patients with >= 1
      assessment without MR4.5 during consolidation (35.0%). In a landmark analysis, 96
      week TFR rates for patients with MR4.5, MR4 (BCR-ABL1IS <= 0.01%) but not MR4.5,
      and MMR but not MR4 at TFR week 12 were 82.6, 23.1, and 0%, respectively. There
      were no reports of disease progression or death due to CML; overall adverse event
      frequency decreased following TFR. Within the follow-up period, TFR did not
      adversely affect disease outcomes. CONCLUSIONS: These results demonstrate the
      feasibility and durability of TFR following frontline nilotinib and emphasize the
      importance of sustained DMR for TFR.

PMID- 29468440
TI  - Incidence and clinical relevance of cage subsidence in anterior cervical
      discectomy and fusion: a systematic review.
AB  - BACKGROUND: The placement of intervertebral cages in anterior cervical discectomy
      (ACDF) supposedly maintains foraminal height. The most commonly reported cage
      related complication is subsidence, although it is unknown whether a correlation
      between subsidence and clinical outcome exists. AIM: To assess the incidence and
      relevance of subsidence. METHODS: Literature searches were performed in PubMed,
      MEDLINE, Embase, Web of Science, COCHRANE, and CENTRAL. The inclusion criteria
      were as follows: >= 20 patients, ADCF with cage, subsidence assessed, and primary
      data. Risk of bias was assessed using adjusted Cochrane checklists. RESULTS:
      Seventy-one studies, comprising 4784 patients, were included. Subsidence was
      generally defined as >= 3-mm loss of height comparing postoperative
      intervertebral heights with heights at last follow-up. Mean incidence of
      subsidence was 21% (range 0-83%). Of all patients, 46% of patients received
      polyether-ether-ketone (PEEK) cages, 31% received titanium cages, 18% received
      cage-screw-combinations, and 5% received polymethyl-methacrylate (PMMA) cages.
      Patients treated with cage-screw-combinations had significantly less subsidence
      than patients treated with PEEK, titanium, or PMMA cages (15.1% vs. 23.5% vs.
      24.9% vs. 30.2%; p < 0.001). Thirteen studies assessed clinical outcome in
      relation to subsidence; the majority did not find a significant correlation. Only
      four studies correlated subsidence to cage size and/or height; no correlation was
      established. CONCLUSIONS: Subsidence in ACDF with cages occurs in 21% of
      patients. The risk for subsidence seems lower using PEEK or titanium cages or
      adding screws. Whether subsidence affects clinical outcome is not satisfactorily
      evaluated in the available literature. Future studies on this correlation are
      warranted in order to establish the additional value of the interposition of a
      cage in ACDF.

PMID- 29468441
TI  - A new minimally invasive technique for lead revision of perc-paddle leads.
AB  - To report on a less-invasive technique for replacing a broken lead in a spinal
      cord stimulation (SCS) device that makes use of St. Jude Medical's "Epiducer"
      device. A 53-year-old woman suffered a loss of stimulation on her internal pulse
      generator (IPG), which was found to have a broken lead. The broken lead was
      withdrawn using the Epiducer device with minimal invasiveness and without pain. A
      new lead was put in place, and successful stimulation using the IPG resumed.
      Follow-up 3 weeks later showed a well-functioning SCS system. An Epiducer can be
      used to revise the SCS system in a minimal invasive way without a new puncture.
      Follow-up study of this technique as well as others for revising an SCS system
      should be encouraged and used in comparison study.

PMID- 29468443
TI  - Deviations from Expectations: A Commentary on Aliev et al.

PMID- 29468442
TI  - A Brief Critique of the TATES Procedure.
AB  - The Trait-based test that uses the Extended Simes procedure (TATES) was developed
      as a method for conducting multivariate GWAS for correlated phenotypes whose
      underlying genetic architecture is complex. In this paper, we provide a brief
      methodological critique of the TATES method using simulated examples and a
      mathematical proof. Our simulated examples using correlated phenotypes show that
      the Type I error rate is higher than expected, and that more TATES p values fall
      outside of the confidence interval relative to expectation. Thus the method may
      result in systematic inflation when used with correlated phenotypes. In a
      mathematical proof we further demonstrate that the distribution of TATES p values
      deviates from expectation in a manner indicative of inflation. Our findings
      indicate the need for caution when using TATES for multivariate GWAS of
      correlated phenotypes.

PMID- 29468444
TI  - The expression of the MSC-marker CD73 and of NF2/Merlin are correlated in
      meningiomas.
AB  - Mesenchymal stem cells (MSC) have been found in various cancers and were
      discussed to influence tumor biology. Cells fulfilling the complete MSC criteria,
      including surface marker expression (CD73, CD90, CD105) and tri-lineage
      differentiation, have been isolated solely from a low percentage of high-grade
      meningiomas. In contrast, pure co-expression of the surface-markers was
      relatively frequent, raising the question for an additional role of these
      membrane proteins in meningiomas. Therefore, here we analyzed the expression of
      CD73, CD90 and CD105 in a series of meningiomas of all grades. Although no
      significant association of any marker with meningeal tumor growth per se or with
      tumor-grade was observed, we detected a positive Pearson correlation (r = 0.55, p
      <= 0.05) in low-grade tumors between CD73 and the most relevant tumor suppressor
      NF2/Merlin, supported by a tendency of lower CD73 expression in cases with
      allelic losses at the NF2-locus, which express significantly lower NF2/Merlin
      mRNA (p <= 0.05). In two pairs of syngenous meningeal or meningioma cell lines
      with or without shRNA-mediated knockdown of NF2/Merlin a nearly complete loss of
      CD73 mRNA expression was observed after the knockdown (p <= 0.001). This
      suggested that the correlation observed in tumors may result from a direct
      functional link between Merlin and CD73. Since CD73 is a 5'-exonucleotidase
      (termed NT5E), we discuss a potential role of NT5E-mediated purinergic signaling
      to modulate actin-cytoskeleton and cell contacts, which may be a functional link
      to NF2/Merlin.

PMID- 29468445
TI  - Tumor microenvironment after biodegradable BCNU wafer implantation: special
      consideration of immune system.
AB  - Biomaterials to treat cancers hold therapeutic potential; however, their
      translation to bedside treatment requires further study. The carmustine (1,3-bis
      (2-chloroethyl)-1-nitrosourea; BCNU) wafer, a biodegradable polymer, currently is
      the only drug that is able to be placed at the surgical site to treat malignant
      tumors. However, how this wafer affects the surrounding tumor microenvironment is
      not well understood to date. We retrospectively reviewed all patients with
      glioblastoma treated with and without BCNU wafers who underwent repeat resection
      at tumor recurrence. We investigated radiological imaging; the interval between
      the two surgeries; and immunohistochemistry of CD3, CD4, CD8, CD20, CD68, FOXP3,
      and PD1. We implanted BCNU wafers in 41 newly diagnosed glioblastoma patients
      after approval of the wafer in Japan. Of them, 14 underwent surgery at recurrence
      and tissue was obtained from around the wafers. The interval between the first
      and second surgeries ranged from 63 to 421 days. The wafer could be observed on
      magnetic resonance imaging at up to 226 days, whereas intraoperatively the
      biodegraded material of the wafer could be found at up to 421 days after the
      initial surgery. Immunohistochemical analysis demonstrated that CD8+ and CD68+
      cells were significantly increased, but FOXP3+ cells did not increase, after
      wafer implantation compared to tissue from cases without wafer implantation. MRI
      data and immune cells, as well as interval between surgeries and immune cells,
      demonstrated positive correlation. These results helped us to understand the
      bioactivity of bioengineered materials and to establish a new approach for
      immunotherapy.

PMID- 29468446
TI  - Cost-effectiveness of the long-term use of temozolomide for treating newly
      diagnosed glioblastoma in Germany.
AB  - Concomitant radiochemotherapy followed by six cycles of temozolomide (= short
      term) is considered as standard therapy for adults with newly diagnosed
      glioblastoma. In contrast, open-end administration of temozolomide until
      progression (= long-term) is proposed by some authors as a viable alternative. We
      aimed to determine the cost-effectiveness of long-term temozolomide therapy for
      patients newly diagnosed with glioblastoma compared to standard therapy. A Markov
      model was constructed to compare medical costs and clinical outcomes for both
      therapy types over a time horizon of 60 months. Transition probabilities for
      standard therapy were calculated from randomized controlled trial data by Stupp
      et al. The data for long-term temozolomide therapy was collected by matching a
      cohort treated in the Department of Neurosurgery at Jena University Hospital.
      Health utilities were obtained from a previous cost utility study. The cost
      perspective was based on health insurance. The base case analysis showed a median
      overall survival of 17.1 months and a median progression-free survival of 7.4
      months for patients in the long-term temozolomide therapy arm. The cost
      effectiveness analysis using all base case parameters in a time-dependent Markov
      model resulted in an incremental effectiveness of 0.022 quality-adjusted life
      years (QALYs). The incremental cost-effectiveness ratio (ICER) was ?351,909/QALY.
      Sensitivity analyses showed that parameters with the most influence on ICER were
      the health state utility of progression in both therapy arms. Although open-ended
      temozolomide therapy is very expensive, the ICER of this therapy is comparable to
      that of the standard temozolomide therapy for patients newly diagnosed with
      glioblastoma.

PMID- 29468447
TI  - The Views of Mental Health Manager Towards the Use of a Family Work Model for
      Psychosis in Guangzhou, China.
AB  - Family Interventions in Psychosis (FIP) have been promoted internationally but
      have been criticised for being based on western cultural models. This paper
      reports on a focus group study with 10 Integrated Mental Health Service Managers
      in Guangzhou, China using thematic analysis. Managers believed FIP might benefit
      families but identified potential difficulties due to (a) families avoiding
      services due to the 'shame' of mental illness (b) unrealistic expectations of
      services amongst families (c) deferral to 'key decision-makers' within families
      when discussing family issues with workers. The findings indicate that FIP work
      should focus on interaction between carers in the first instance with service
      users being introduced into sessions at a later date and that more attention
      needs to be given by the research community to how FIP may be adapted to cultural
      norms within China.

PMID- 29468449
TI  - Effect of Tungsten Nanolayer Coating on Si Electrode in Lithium-ion Battery.
AB  - Tungsten (W) was coated onto a silicon (Si) anode at the nanoscale via the
      physical vaporization deposition method (PVD) to enhance its electrochemical
      properties. The characteristics of the electrode were identified by scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), energy
      dispersive X-ray analysis, and electron probe X-ray microanalysis. With the
      electrochemical property analysis, the first charge capacities of the W-coated
      and uncoated electrode cells were 2558 mAh g- 1 and 1912 mAh g- 1, respectively.
      By the 50th cycle, the capacity ratios were 61.1 and 25.5%, respectively.
      Morphology changes in the W-coated Si anode during cycling were observed using
      SEM and TEM, and electrochemical characteristics were examined through impedance
      analysis. Owing to its conductivity and mechanical properties from the atomic W
      layer coating through PVD, the electrode improved its cyclability and preserved
      its structure from volumetric demolition.

PMID- 29468448
TI  - Current State of Fetal Intervention for Lower Urinary Tract Obstruction.
AB  - PURPOSE OF THE REVIEW: In this article, we explore the origins of intervention of
      fetal lower urinary tract obstruction, and we specifically discuss the background
      and recent outcomes of vesicoamniotic shunt placement and fetal cystoscopy. The
      article seeks to provide a comprehensive overview of the field while bringing the
      reader quickly up to speed on the pertinent literature and the critical data that
      are available to guide decision-making regarding intervention. RECENT FINDINGS:
      Appropriate patient selection for fetal intervention remains challenging despite
      advances in prenatal imaging. Both a randomized controlled trial and multiple
      systematic reviews show evidence of a perinatal survival benefit following fetal
      intervention but rates of renal morbidity remain very high. Despite 30 years of
      research, fetal lower urinary tract obstruction remains a difficulty entity to
      treat. Intervention may lead to survival, but physicians and caregivers must
      remain alert for the distinct possibility of long-term renal morbidity in
      survivors.

PMID- 29468450
TI  - Migraine is first cause of disability in under 50s: will health politicians now
      take notice?

PMID- 29468451
TI  - Identification of porcine epidemic diarrhea virus variant with a large spike gene
      deletion from a clinical swine sample in the United States.
AB  - Two genetically different porcine epidemic diarrhea virus (PEDV) strains have
      been identified in the USA: US prototype (also called non-S INDEL) and S INDEL
      PEDVs. In February 2017, a PEDV variant (USA/OK10240-8/2017) was identified in a
      rectal swab from a sow farm in Oklahoma, USA. Complete genome sequence analyses
      indicated this PEDV variant was genetically similar to US non-S INDEL strain but
      had a continuous 600-nt (200-aa) deletion in the N-terminal domain of the spike
      gene compared to non-S INDEL PEDVs. This is the first report of detecting PEDV
      bearing large spike gene deletion in clinical swine samples in the USA.

PMID- 29468452
TI  - Leptin regulates the pro-inflammatory response in human epidermal keratinocytes.
AB  - The role of leptin in cutaneous wound healing process has been suggested in
      genetically obese mouse studies. However, the molecular and cellular effects of
      leptin on human epidermal keratinocytes are still unclear. In this study, the
      whole-genome-scale microarray analysis was performed to elucidate the effect of
      leptin on epidermal keratinocyte functions. In the leptin-treated normal human
      keratinocytes (NHKs), we identified the 151 upregulated and 53 downregulated
      differentially expressed genes (DEGs). The gene ontology (GO) enrichment analysis
      with the leptin-induced DEGs suggests that leptin regulates NHKs to promote pro
      inflammatory responses, extracellular matrix organization, and angiogenesis.
      Among the DEGs, the protein expression of IL-8, MMP-1, fibronectin, and S100A7,
      which play roles in which is important in the regulation of cutaneous
      inflammation, was confirmed in the leptin-treated NHKs. The upregulation of the
      leptin-induced proteins is mainly regulated by the STAT3 signaling pathway in
      NHKs. Among the downregulated DEGs, the protein expression of nucleosome assembly
      associated centromere protein A (CENPA) and CENPM was confirmed in the leptin
      treated NHKs. However, the expression of CENPA and CENPM was not coupled with
      those of other chromosome passenger complex like Aurora A kinase, INCENP, and
      survivin. In cell growth kinetics analysis, leptin had no significant effect on
      the cell growth curves of NHKs in the normal growth factor-enriched condition.
      Therefore, leptin-dependent downregulation of CENPA and CENPM in NHKs may not be
      directly associated with mitotic regulation during inflammation.

PMID- 29468453
TI  - Poor return on investment: investigating the barriers that cause low
      credentialing yields in a resource-limited clinical ultrasound training
      programme.
AB  - BACKGROUND: Clinical ultrasound is commonly used in medical practices worldwide
      due to the multiple benefits the modality offers clinicians. Rigorous
      credentialing standards are necessary to safeguard patients against operator
      errors. The purpose of the study was to establish and analyse the barriers that
      specifically lead to poor credentialing success within a resource-limited
      clinical ultrasound training programme. METHODS: An electronic cross-sectional
      survey was e-mailed to all trainees who attended the introductory clinical
      ultrasound courses held in Cape Town since its inception in 2009 to 2013. All
      trainees were followed until they completed their training programme in 2015.
      RESULTS: Only one fifth of trainees (n = 43, 19.7%), who entered the Cape Town
      training programme, credentialed successfully. Ninety (n = 90, 41.3%) trainees
      responded to the survey. Eighty-six (n = 86) surveys were included for analysis.
      Time constraints were the highest ranked barrier amongst all trainees. Access
      barriers (to trainers and ultrasound machines) were the second highest ranked
      amongst the non-credentialed group. A combination between access and logistical
      barriers (e.g. difficulty in finding patients with pathology to scan) were the
      second highest ranked in the credentialed group. CONCLUSIONS: Access barriers
      conspire to burden the Cape Town clinical ultrasound training programme. Novel
      solutions are necessary to overcome these access barriers to improve future
      credentialing success.

PMID- 29468454
TI  - Randomized phase II study of anastrozole plus tegafur-uracil as neoadjuvant
      therapy for ER-positive breast cancer in postmenopausal Japanese women (Neo-ACET
      BC).
AB  - PURPOSE: This phase II study evaluated the efficacy and safety of anastrozole
      concurrent with tegafur/uracil (UFT) as neoadjuvant therapy for ER-positive
      postmenopausal breast cancer. METHODS: Postmenopausal Japanese women with ER
      positive, HER2-negative, T2,N0-1,M0 breast cancer seen at tertiary hospitals were
      eligible for this open-label, randomized, multicenter study. Patients were
      randomized 1:1 by minimization to orally receive either anastrozole (1 mg once
      daily) plus UFT (tegafur/uracil combination in 1:4 molar ratio; 270 mg/m2/day in
      two divided doses) or anastrozole (as above) alone for 24 weeks. Tumor response
      was assessed by investigator and central review as per RECIST v1.1. The primary
      endpoint was the proportion of patients with best overall response of CR or PR
      [clinical response rate (RR)] determined by central radiologic review. RESULTS:
      The study was prematurely terminated due to Grade >= 3 liver dysfunction reported
      in 3 patients receiving anastrozole/UFT. Of 57 patients randomized before
      termination (29 anastrozole/UFT, 28 anastrozole), all were analyzed for safety
      and 56 (28 each group) for tumor response. Compared with anastrozole alone,
      anastrozole/UFT did not achieve significantly higher RR [39.3% (90% CI 23.8
      56.5%) vs 14.3% (90% CI 5.0-29.8%); p = 0.0683, Fisher's exact test], but
      produced significantly greater tumor shrinkage (mean tumor reduction rate 31.0
      vs. 14.2%; p = 0.0181, unpaired t-test). Grade >= 3 adverse events were more
      common with anastrozole/UFT than with anastrozole (17.2 vs. 0%). CONCLUSION:
      Although the study was terminated owing to the altered liver function, it showed
      that there was a trend to greater shrinkage of tumor in the combination group for
      ER-positive, HER2-negative postmenopausal breast cancer.

PMID- 29468455
TI  - Evaluation of hepatic impairment on pharmacokinetics and safety of crizotinib in
      patients with advanced cancer.
AB  - PURPOSE: This phase 1 study evaluated the effect of hepatic impairment on
      pharmacokinetics and safety of crizotinib in patients with advanced cancer.
      METHODS: Patients were dosed according to hepatic function classified by modified
      National Cancer Institute Organ Dysfunction Working Group criteria and group
      assignment [normal (A1 and A2), mild (B), moderate (C1 and C2), or severe (D)].
      Primary pharmacokinetic endpoints included area under the concentration-time
      curve as daily exposure (AUCdaily) and maximum plasma concentration (Cmax) at
      steady state. Safety endpoints included types, incidence, seriousness, and
      relationship to crizotinib of adverse events. RESULTS: The AUCdaily and Cmax in
      patients with normal liver function were 7107 ng h/mL and 375.1 ng/mL (A1) and
      5422 ng h/mL and 283.9 ng/mL (A2), respectively. The AUCdaily and Cmax ratios of
      adjusted geometric means for Groups B, C2, and D versus Group A1 were 91.12 and
      91.20, 114.08 and 108.87, and 64.47 and 72.63, respectively. Any grade treatment
      related adverse events (TRAEs) occurred in 75% of patients; grade 3/4 TRAEs
      occurred in 25%, including fatigue (6%), hyponatremia (5%), and
      hyperbilirubinemia (3%). CONCLUSIONS: No adjustment to the approved 250 mg twice
      daily (BID) dose of crizotinib is recommended for patients with mild hepatic
      impairment. The recommended dose is 200 mg BID for patients with moderate hepatic
      impairment, and the dose should not exceed 250 mg daily for patients with severe
      hepatic impairment. Adverse events appeared consistent among the hepatic
      impairment groups. CLINICAL TRIAL REGISTRATION NO: NCT01576406.

PMID- 29468456
TI  - Phase 1, open-label, dose-escalation study of sorafenib in combination with
      eribulin in patients with advanced, metastatic, or refractory solid tumors.
AB  - Combining sorafenib and eribulin mesylate may provide synergistic antitumor
      activities with limited overlapping toxicities. This phase 1b, open-label, dose
      escalation study evaluated safety, pharmacokinetics, maximum tolerated
      dose/recommended phase 2 dose (MTD/RP2D), and preliminary efficacy of sorafenib
      plus standard-dose eribulin mesylate in patients with advanced, metastatic, or
      refractory tumors. Patients received sorafenib 200 mg twice daily (BID; n = 5),
      600 mg/day (n = 8), and 400 mg BID (MTD; n = 27). Dose-limiting toxicities were
      increased alanine aminotransferase and acute coronary syndrome (both grade 3) in
      the 400-mg BID dose-escalation and expansion cohorts, respectively. No
      significant increase in mean QTcF duration was observed with eribulin plus
      sorafenib versus eribulin alone; there were no drug-drug interactions. Five
      patients achieved partial response; 16 achieved stable disease. The combination
      of sorafenib and eribulin mesylate presented no unexpected safety concerns and no
      significant impact on QT/QTc intervals or drug-drug interactions. Sorafenib 400
      mg BID plus standard-dose eribulin is the RP2D.

PMID- 29468457
TI  - Obesity and Stress Urinary Incontinence: Impact on Pathophysiology and Treatment.
AB  - PURPOSE OF REVIEW: Obesity is highly prevalent and is associated with stress
      urinary incontinence (SUI). The purposes of this review are to assess the
      pathophysiology of SUI in the obese female and review the outcomes of weight loss
      and anti-incontinence surgery in this population. RECENT FINDINGS: While
      increased intra-abdominal pressure appears to be the common pathophysiologic link
      between obesity and SUI, neurogenic and metabolic pathways have been proposed.
      Both surgical and non-surgical weight loss continue to have beneficial effects on
      SUI; however, long-term outcomes are largely absent. Midurethral sling (MUS)
      surgery is largely effective in the obese population, with a complication profile
      similar to that in non-obese women. Obesity has been shown to be a risk factor
      for failure of MUS. While weight loss should be the primary modality to improve
      SUI in the obese woman, MUS remains an effective and safe option in those women
      undertaking surgery.

PMID- 29468458
TI  - Axon Initial Segment Structural Plasticity is Involved in Seizure Susceptibility
      in a Rat Model of Cortical Dysplasia.
AB  - Cortical dysplasia is the most common etiology of intractable epilepsy. Both
      excitability changes in cortical neurons and neural network reconstitution play a
      role in cortical dysplasia epileptogenesis. Recent research shows that the axon
      initial segment, a subcompartment of the neuron important to the shaping of
      action potentials, adjusts its position in response to changes in input, which
      contributes to neuronal excitability and local circuit balance. It is unknown
      whether axon initial segment plasticity occurs in neurons involved in seizure
      susceptibility in cortical dysplasia. Here, we developed a "Carmustine"-
      "pilocarpine" rat model of cortical dysplasia and show that it exhibits a lower
      seizure threshold, as indicated by behavior studies and electroencephalogram
      monitoring. Using immunofluorescence, we measured the axon initial segment
      positions of deep L5 somatosensory neurons and show that it is positioned closer
      to the soma after acute seizure, and that this displacement is sustained in the
      chronic phase. We then show that Nifedipine has a dose-dependent protective
      effect against axon initial segment displacement and increased seizure
      susceptibility. These findings further our understanding of the pathophysiology
      of seizures in cortical dysplasia and suggests Nifedipine as a potential
      therapeutic agent.

PMID- 29468459
TI  - Rht24 reduces height in the winter wheat population 'Solitar * Bussard' without
      adverse effects on Fusarium head blight infection.
AB  - KEY MESSAGE: The dwarfing gene Rht24 on chromosome 6A acts in the wheat
      population 'Solitar * Bussard', considerably reducing plant height without
      increasing Fusarium head blight severity and delaying heading stage. The
      introduction of the Reduced height (Rht)-B1 and Rht-D1 semi-dwarfing genes led to
      remarkable increases in wheat yields during the Green Revolution. However, their
      utilization also brings about some unwanted characteristics, including the
      increased susceptibility to Fusarium head blight. Thus, Rht loci that hold the
      potential to reduce plant height in wheat without concomitantly increasing
      Fusarium head blight (FHB) susceptibility are urgently required. The biparental
      population 'Solitar * Bussard' fixed for the Rht-1 wild-type alleles, but
      segregating for the recently described gibberellic acid (GA)-sensitive Rht24
      gene, was analyzed to identify quantitative trait loci (QTL) for FHB severity,
      plant height, and heading date and to evaluate the effect of the Rht24 locus on
      these traits. The most prominent QTL was Rht24 on chromosome 6A explaining 51% of
      genotypic variation for plant height and exerting an additive effect of - 4.80
      cm. For FHB severity three QTL were detected, whereas five and six QTL were found
      for plant height and heading date, respectively. No FHB resistance QTL was co
      localized with QTL for plant height. Unlike the Rht-1 semi-dwarfing alleles,
      Rht24b did not significantly affect FHB severity. This demonstrates that the
      choice of semi-dwarfing genes used in plant breeding programs is of utmost
      consideration where resistance to FHB is an important breeding target.

PMID- 29468461
TI  - Flavonoid intake from fruit and vegetables during adolescence is prospectively
      associated with a favourable risk factor profile for type 2 diabetes in early
      adulthood.
AB  - PURPOSE: Flavonoid consumption during adolescence could contribute to preventing
      adult onset of type 2 diabetes mellitus. We investigated the prospective
      association between habitual intake of flavonoids from fruit and vegetables
      (FlavFV) during adolescence and risk markers of type 2 diabetes in early
      adulthood. METHODS: This analysis included participants of the DONALD Study, who
      had provided a fasting blood sample in adulthood (18-39 years), data on FlavFV
      intake during adolescence (females: 9-15 years, males: 10-16 years) and relevant
      covariates. Habitual FlavFV-intake was either estimated using repeated 3-day
      weighed dietary records (n = 268), or the validated biomarker hippuric acid (uHA)
      excretion in repeated 24-h urine samples (n = 241). Multivariable linear
      regressions were performed to analyse the prospective associations of FlavFV or
      uHA with homeostasis model assessment insulin sensitivity (HOMA2-%S), hepatic
      steatosis index (HSI), fatty liver index (FLI) and a pro-inflammatory score.
      RESULTS: Higher FlavFV-intake was independently related to higher HOMA2-%S among
      females (Ptrend = 0.03), but not among males. Both FlavFV-intake and uHA
      excretion were inversely associated with HSI (Ptrend < 0.0001 and Ptrend = 0.02,
      respectively) and the pro-inflammatory score (Ptrend = 0.02 and Ptrend = 0.008,
      respectively), but not with FLI. CONCLUSIONS: Our data indicate that flavonoid
      consumption from fruit and vegetables during adolescence is associated with a
      favourable risk factor profile for type 2 diabetes in early adulthood.

PMID- 29468460
TI  - Two dominant loci determine resistance to Phomopsis cane lesions in F1 families
      of hybrid grapevines.
AB  - KEY MESSAGE: Rapid characterization of novel NB-LRR-associated resistance to
      Phomopsis cane spot on grapevine using high-throughput sampling and low-coverage
      sequencing for genotyping, locus mapping and transcriptome analysis provides
      insights into genetic resistance to a hemibiotrophic fungus. Phomopsis cane and
      leaf spot, caused by the hemibiotrophic fungus Diaporthe ampelina (syn =
      Phomopsis viticola), reduces the productivity in grapevines. Host resistance was
      studied on three F1 families derived from crosses involving resistant genotypes
      'Horizon', Illinois 547-1, Vitis cinerea B9 and V. vinifera 'Chardonnay'. All
      families had progeny with extremely susceptible phenotypes, developing lesions on
      both dormant canes and maturing fruit clusters. Segregation of symptoms was
      observed under natural levels of inoculum in the field, while phenotypes on green
      shoots were confirmed under controlled inoculations in greenhouse. High-density
      genetic maps were used to localize novel qualitative resistance loci named Rda1
      and Rda2 from V. cinerea B9 and 'Horizon', respectively. Co-linearity between
      reference genetic and physical maps allowed localization of Rda2 locus between
      1.5 and 2.4 Mbp on chromosome 7, and Rda1 locus between 19.3 and 19.6 Mbp of
      chromosome 15, which spans a cluster of five NB-LRR genes. Further dissection of
      this locus was obtained by QTL mapping of gene expression values 14 h after
      inoculation across a subset of the 'Chardonnay' * V. cinerea B9 progeny. This
      provided evidence for the association between transcript levels of two of these
      NB-LRR genes with Rda1, with increased NB-LRR expression among susceptible
      progeny. In resistant parent V. cinerea B9, inoculation with D. ampelina was
      characterized by up-regulation of SA-associated genes and down-regulation of
      ethylene pathways, suggesting an R-gene-mediated response. With dominant effects
      associated with disease-free berries and minimal symptoms on canes, Rda1 and Rda2
      are promising loci for grapevine genetic improvement.

PMID- 29468462
TI  - Modulation by hydroxytyrosol of oxidative stress and antitumor activities of
      paclitaxel in breast cancer.
AB  - PURPOSE: The main objective of this study was to test the therapeutic potential
      of hydroxytyrosol and its combination with paclitaxel in breast cancer on
      oxidative stress status. METHODS: Impact on proliferation rates of different
      chemotherapy administration patterns was assayed in MCF-7 and MDA-MB-231 breast
      cancer cell lines. Breast tumor-bearing rats were randomly assigned to Control,
      Hydroxytyrosol, Paclitaxel and Paclitaxel plus hydroxytyrosol groups, for 6
      weeks. Tumor volume, cell proliferation and several systemic oxidative stress
      parameters were measured. Anti-proliferative activity in vitro experiments was
      correlated with in vivo experiments. RESULTS: Combination group did significantly
      reduce tumor volume when compared with paclitaxel alone. Additionally, the
      combination improved the antioxidant status without compromising the antitumor
      activity of standard chemotherapy. CONCLUSION: These findings reveal for the
      first time that hydroxytyrosol is an active partner in combined therapies with
      paclitaxel against breast cancer. Combination with hydroxytyrosol would also
      ensure a less oxidative impact of chemotherapeutic drugs that could potentially
      improve patient wellness.

PMID- 29468463
TI  - Detecting seasonal and cyclical trends in agricultural runoff water quality
      hypothesis tests and block bootstrap power analysis.
AB  - Seasonal and cyclic trends in nutrient concentrations at four agricultural
      drainage ditches were assessed using a dataset generated from a multivariate,
      multiscale, multiyear water quality monitoring effort in the agriculturally
      dominant Lower Rio Grande Valley (LRGV) River Watershed in South Texas. An
      innovative bootstrap sampling-based power analysis procedure was developed to
      evaluate the ability of Mann-Whitney and Noether tests to discern trends and to
      guide future monitoring efforts. The Mann-Whitney U test was able to detect
      significant changes between summer and winter nutrient concentrations at sites
      with lower depths and unimpeded flows. Pollutant dilution, non-agricultural
      loadings, and in-channel flow structures (weirs) masked the effects of
      seasonality. The detection of cyclical trends using the Noether test was highest
      in the presence of vegetation mainly for total phosphorus and oxidized nitrogen
      (nitrite + nitrate) compared to dissolved phosphorus and reduced nitrogen (total
      Kjeldahl nitrogen-TKN). Prospective power analysis indicated that while increased
      monitoring can lead to higher statistical power, the effect size (i.e., the total
      number of trend sequences within a time-series) had a greater influence on the
      Noether test. Both Mann-Whitney and Noether tests provide complementary
      information on seasonal and cyclic behavior of pollutant concentrations and are
      affected by different processes. The results from these statistical tests when
      evaluated in the context of flow, vegetation, and in-channel hydraulic
      alterations can help guide future data collection and monitoring efforts. The
      study highlights the need for long-term monitoring of agricultural drainage
      ditches to properly discern seasonal and cyclical trends.

PMID- 29468464
TI  - Characterizing Intervention Strategies Used in Community-Based Mental Health Care
      for Infants and Their Families.
AB  - Mental health interventions for infants typically target high-risk groups and can
      prevent long-term negative outcomes. Despite federal initiatives promoting early
      intervention, minimal research has examined usual care services for infants,
      which is important to improve routine care. The current study characterized usual
      care practices in infant mental health through the adaptation and administration
      of a provider survey. Providers (n = 126) reported using a wide range of
      intervention strategies and few intervention programs with varied evidence.
      Findings can inform future research to identify quality improvement targets of
      usual mental health care for high-risk infants and their families.

PMID- 29468465
TI  - ASNC President's Message.

PMID- 29468466
TI  - Evolving, innovating, and revolutionary changes in cardiovascular imaging: We've
      only just begun!
AB  - In this review, we highlight the need for innovation and creativity to reinvent
      the field of nuclear cardiology. Revolutionary ideas brought forth today are
      needed to create greater value in patient care and highlight the need for more
      contemporary evidence supporting the use of nuclear cardiology practices. We put
      forth discussions on the need for disruptive innovation in imaging-guided care
      that places the imager as a central force in care coordination. Value-based
      nuclear cardiology is defined as care that is both efficient and effective. Novel
      testing strategies that defer testing in lower risk patients are examples of the
      kind of innovation needed in today's healthcare environment. A major focus of
      current research is the evolution of the importance of ischemia and the
      prognostic significance of non-obstructive atherosclerotic plaque and coronary
      microvascular dysfunction. Embracing novel paradigms, such as this, can aid in
      the development of optimal strategies for coronary disease management. We hope
      that our article will spurn the field toward greater innovation and focus on
      transformative imaging leading the way for new generations of novel
      cardiovascular care.

PMID- 29468468
TI  - The long way to defeating Chagas cardiomyopathy.

PMID- 29468467
TI  - Adverse effects associated with regadenoson myocardial perfusion imaging.

PMID- 29468469
TI  - Technical aspects of cardiac PET/MRI.
AB  - PET/MRI is a novel modality that enables to combine PET and MR images, and has
      significant potential to evaluate various cardiac diseases through the
      combination of PET molecular imaging and MRI functional imaging. Precise
      management of technical issues, however, is necessary for cardiac PET/MRI. This
      article describes several technical points, including patient preparation, MR
      attenuation correction, parallel acquisition of PET with MRI, clinical aspects,
      and image quality control.

PMID- 29468470
TI  - Cardiac adrenergic neuronal activity, sleep apnea, and potential therapeutic role
      of nocturnal ventilatory assistance in patients with heart failure.

PMID- 29468471
TI  - Electrochemical Synthesis of Battery Electrode Materials from Ionic Liquids.
AB  - Electrode materials as well as the electrolytes play a decisive role in batteries
      determining their performance, safety, and lifetime. In the last two decades,
      different types of batteries have evolved. A lot of work has been done on lithium
      ion batteries due to their technical importance in consumer electronics, however,
      the development of post-lithium systems has become a focus in recent years. This
      chapter gives an overview of various battery materials, primarily focusing on
      development of electrode materials in ionic liquids via electrochemical route and
      using ionic liquids as battery electrolyte components.

PMID- 29468472
TI  - Editors introduction: biobanks as sites of bio-objectification.

PMID- 29468474
TI  - Estimation of forest aboveground biomass and uncertainties by integration of
      field measurements, airborne LiDAR, and SAR and optical satellite data in Mexico.
AB  - BACKGROUND: Information on the spatial distribution of aboveground biomass (AGB)
      over large areas is needed for understanding and managing processes involved in
      the carbon cycle and supporting international policies for climate change
      mitigation and adaption. Furthermore, these products provide important baseline
      data for the development of sustainable management strategies to local
      stakeholders. The use of remote sensing data can provide spatially explicit
      information of AGB from local to global scales. In this study, we mapped national
      Mexican forest AGB using satellite remote sensing data and a machine learning
      approach. We modelled AGB using two scenarios: (1) extensive national forest
      inventory (NFI), and (2) airborne Light Detection and Ranging (LiDAR) as
      reference data. Finally, we propagated uncertainties from field measurements to
      LiDAR-derived AGB and to the national wall-to-wall forest AGB map. RESULTS: The
      estimated AGB maps (NFI- and LiDAR-calibrated) showed similar goodness-of-fit
      statistics (R2, Root Mean Square Error (RMSE)) at three different scales compared
      to the independent validation data set. We observed different spatial patterns of
      AGB in tropical dense forests, where no or limited number of NFI data were
      available, with higher AGB values in the LiDAR-calibrated map. We estimated much
      higher uncertainties in the AGB maps based on two-stage up-scaling method (i.e.,
      from field measurements to LiDAR and from LiDAR-based estimates to satellite
      imagery) compared to the traditional field to satellite up-scaling. By removing
      LiDAR-based AGB pixels with high uncertainties, it was possible to estimate
      national forest AGB with similar uncertainties as calibrated with NFI data only.
      CONCLUSIONS: Since LiDAR data can be acquired much faster and for much larger
      areas compared to field inventory data, LiDAR is attractive for repetitive large
      scale AGB mapping. In this study, we showed that two-stage up-scaling methods for
      AGB estimation over large areas need to be analyzed and validated with great
      care. The uncertainties in the LiDAR-estimated AGB propagate further in the wall
      to-wall map and can be up to 150%. Thus, when a two-stage up-scaling method is
      applied, it is crucial to characterize the uncertainties at all stages in order
      to generate robust results. Considering the findings mentioned above LiDAR can be
      used as an extension to NFI for example for areas that are difficult or not
      possible to access.

PMID- 29468475
TI  - A DFT study of the catalytic pyrolysis of benzaldehyde on ZnO, gamma-Al2O3, and
      CaO models.
AB  - The catalytic pyrolysis pathways of carbonyl compounds in coal were
      systematically studied using density functional theory (DFT), with benzaldehyde
      (C6H5CHO) employed as a coal-based model compound and ZnO, gamma-Al2O3, and CaO
      as catalysts. The results show that the products of both pyrolysis and catalytic
      pyrolysis are C6H6 and CO. However, the presence of any of the catalysts changes
      the reaction pathway and reduces the energy barrier, indicating that these
      catalysts promote C6H5CHO decomposition. Graphical abstract The presence of
      catalysts changes the reaction pathway and the energy barrier decreases in the
      order Ea (no catalyst)> Ea (CaO)> Ea (gamma-Al2O3)> Ea (ZnO), indicating that
      these catalysts promote C6H5CHO decomposition.

PMID- 29468473
TI  - Clinical aspects of myocardial fibrosis in adults with Ebstein's anomaly.
AB  - Heart failure and arrhythmia are common complications in adults with Ebstein's
      anomaly. They may result not only from hemodynamic alterations, but also from
      myocardial fibrosis. Late gadolinium enhancement (LGE) by CMR enables the
      evaluation of myocardial fibrosis. The aim of the study was to asses the presence
      of LGE and its relation to clinical outcome. We studied a group of 37 unoperated
      adults aged 43.0 +/- 14.4 years with Ebstein's anomaly from the congenital heart
      disease outpatient clinic. Study protocol included: cardiopulmonary test,
      assessment of supraventricular arrhythmia (SVA), and CMR with evaluation of
      cardiac chambers' morphology and function, and presence of LGE. Variables
      following normal distribution were shown as mean +/- SD if otherwise median
      (range) was applied. Fibrosis was found in 18 patients (48.6%) and was
      distributed as follows: 12 patients (32.4%) in the right atrium, 12 (32.4%) in
      the atrialized right ventricle, and 2 (5.4%) in the functional right ventricle.
      In patients with fibrosis, the tricuspid regurgitation fraction was bigger (48.3
      +/- 19.7 vs. 36.1 +/- 22.6%, p = 0.048) and SVA was more frequent [12 (66.7%) vs.
      6 (31.6%), p = 0.046] when compared to patients without fibrosis. However,
      exercise capacity did not differ between patients with and without LGE (peak VO2
      24.0 +/- 4.7 vs. 23.7 +/- 4.4, p = 0.87). In adults with Ebstein's anomaly
      fibrosis estimated by LGE-CMR was localized in the right atrium and the right
      ventricle only. Volume overload resulting from tricuspid regurgitation might be a
      factor conducive to fibrosis. Myocardial fibrosis did not influence exercise
      capacity. Association between myocardial fibrosis and supraventricular arrhythmia
      was confirmed.

PMID- 29468476
TI  - Current Treatment of Pediatric Bladder and Prostate Rhabdomyosarcoma.
AB  - PURPOSE OF REVIEW: Rhabdomyosarcoma (RMS) is the most common sarcoma diagnosed in
      the first 20 years of life; bladder/prostate (BP) RMS accounts for 5% of all
      cases. Through efforts from multiple cooperative study groups, survival has
      improved significantly. This article aims to review the complex RMS
      classification system and treatment of BP RMS, with a focus on developing aspects
      of treatment. RECENT FINDINGS: Recent advancements in technology are responsible
      for most of the progress in RMS treatment. PET-CT scanning has been shown to be
      superior to conventional metastatic workup. The use of proton beam therapy and
      brachytherapy to reduce the side effects of radiation is also showing promise.
      All cooperative oncology groups agree on surgical biopsy for diagnosis and
      staging of BP RMS. Patients are then grouped and risk classified before receiving
      chemotherapy. Regardless of local control strategy, oncologic outcomes appear to
      be similar for BP RMS. Alternative treatment strategies, which remain unproven,
      include brachytherapy and proton therapy.

PMID- 29468477
TI  - Ethanol extract of Rehmannia glutinosa exerts antidepressant-like effects on a
      rat chronic unpredictable mild stress model by involving monoamines and BDNF.
AB  - The dried roots of Rehmannia glutinosa Libosch. (Scrophulariaceae) are of both
      medicinal and nutritional importance. Our previous study has found that the 80%
      ethanol extract of R. glutinosa (RGEE) produced antidepressant-like activities in
      mouse behavioral despair depression models. However, its mechanisms are still
      unclear. The present study aimed to observe the antidepressant-like mechanisms of
      RGEE on a rat chronic unpredictable mild stress (CUMS) model by involving
      monoaminergic neurotransmitters and brain-derived neurotrophic factor (BDNF).
      CUMS-stressed rats were orally given RGEE daily (150, 300, and 600 mg/kg) or
      fluoxetine hydrochloride (FH) for 3 weeks after starting the CUMS procedure.
      Sucrose preference test was carried out to observe depression-like behavior, and
      serum and brain tissues were used for neurochemical and fluorescent quantitative
      reverse transcription PCR analysis. Results demonstrated that CUMS induced
      depression-like behavior, whereas RGEE and FH administration inhibited this
      symptom. Furthermore, CUMS caused excessively elevated levels of serum
      corticosterone (CORT), an index of hypothalamic-pituitary-adrenal (HPA) axis
      hyperactivity, in a manner attenuated by RGEE and FH administration. RGEE
      administration also further elevated monoamine neurotransmitters and BDNF levels,
      up-regulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB)
      in hippocampus of rats suffering CUMS. Together, our findings suggest that RGEE
      can improve CUMS-evoked depression-like behavior, and indicate its mechanisms may
      partially be associated with restoring HPA axis dysfunctions, enhancing
      monoamineergic nervous systems, and up-regulating BDNF and TrkB expression.

PMID- 29468478
TI  - Does Trabecular Bone Score (TBS) improve the predictive ability of FRAX(r) for
      major osteoporotic fractures according to the Japanese Population-Based
      Osteoporosis (JPOS) cohort study?
AB  - This study examined whether bone microarchitecture determined by Trabecular Bone
      Score (TBS) is associated with the risk of major osteoporotic fractures
      independent of FRAX(r) in Japanese women. Participants included 1541 women aged
      >= 40 at baseline. Major osteoporotic fractures during a 10-year follow-up period
      were documented by the Japanese Population-based Osteoporosis Cohort Study. TBS
      and areal bone mineral density (aBMD) were calculated for the same spinal regions
      at baseline. To compare the predictive ability of FRAX(r) model when used alone
      versus in combination with TBS, Akaike information criterion (AIC), the area
      under the receiver operating characteristic curve (AUC), net reclassification
      improvement (NRI), and integrated discrimination improvement (IDI) were
      calculated. We identified 67 events of major osteoporotic fractures. The skeletal
      sites of the first fracture event were as follows: hip (11), vertebrae (13),
      radius (42), and humerus (1). The model incorporating FRAX(r) [1.35 (95% CI 1.09
      1.67) for 1 standard deviation (SD) increase] with TBS [1.46 (95% CI 1.08-1.98)
      for 1 SD decrease] demonstrated better fit compared to a model consisting of FRAX
      alone (AIC 528.6 vs 532.7). NRI values for classification accuracy showed
      significant improvements in the FRAX(r) and TBS model, as compared to FRAX(r)
      alone [0.299 (95% CI 0.056-0.541)]. However, there were no significant
      differences in AUC or IDI between these models. The TBS score is associated with
      a risk of major osteoporotic fracture independent of FRAX(r) score obtained with
      or without BMD values among Japanese women during a 10-year follow-up period.

PMID- 29468479
TI  - Cell encapsulation utilizing PEG-fibrinogen hydrogel supports viability and
      enhances productivity under stress conditions.
AB  - Recent advances in the bioengineering field have introduced new opportunities
      enabling cell encapsulation in three-dimensional (3D) structures using either
      various natural or synthetic materials. However, such hydrogel scaffolds have not
      been fully biocompatible for cell cultivation due to the lack of physical
      stability or bioactivity. Here, we utilized a uniquely fabricated semi-synthetic
      3D polyethylene glycol-fibrinogen (PEG-Fb) hydrogel scaffold, which exhibits both
      high stability and high bioactivity, to encapsulate HEK293 cells for the
      production of human recombinant acetylcholine esterase (AChE). To examine the
      beneficial bioactive effect of the PEG-Fb scaffold over 2D surfaces, an
      experimental system was established to compare the viability, proliferation and
      AChE secretion of encapsulated cells versus non-encapsulated surface-adherent
      cells in serum starvation. Our results show that the transfer of surface-adherent
      HEK293 cells from fully enriched medium with 10% FCS to 0.2% FCS resulted in an
      eightfold reduction in cell number and a fourfold reduction in AChE production.
      In contrast, the encapsulated cells were highly viable and about twofold more
      efficient in AChE production. In addition, they had round morphology with a
      twofold larger cell diameter, supporting the observation of increased AChE
      production. These results suggest a role of the PEG-Fb scaffold in providing a
      supportive microenvironment in reduced serum conditions that enhances
      encapsulated cell functions, opening new directions to study the implementation
      of this platform in large-scale pharmaceutical protein production.

PMID- 29468480
TI  - Phenotypic Plasticity of Cuticular Hydrocarbon Profiles in Insects.
AB  - The insect integument is covered by cuticular hydrocarbons (CHCs) which provide
      protection against environmental stresses, but are also used for communication.
      Here we review current knowledge on environmental and insect-internal factors
      which shape phenotypic plasticity of solitary living insects, especially
      herbivorous ones. We address the dynamics of changes which may occur within
      minutes, but may also last weeks, depending on the species and conditions. Two
      different modes of changes are suggested, i.e. stepwise and gradual. A switch
      between two distinct environments (e.g. host plant switch by phytophagous
      insects) results in stepwise formation of two distinct adaptive phenotypes, while
      a gradual environmental change (e.g. temperature gradients) induces a gradual
      change of numerous adaptive CHC phenotypes. We further discuss the ecological and
      evolutionary consequences of phenotypic plasticity of insect CHC profiles by
      addressing the question at which conditions is CHC phenotypic plasticity
      beneficial. The high plasticity of CHC profiles might be a trade-off for insects
      using CHCs for communication. We discuss how insects cope with the challenge to
      produce and "understand" a highly plastic, environmentally dependent CHC pattern
      that conveys reliable and comprehensible information. Finally, we outline how
      phenotypic plasticity of CHC profiles may promote speciation in insects that rely
      on CHCs for mate recognition.

PMID- 29468481
TI  - Licarin A induces cell death by activation of autophagy and apoptosis in non
      small cell lung cancer cells.
AB  - Lung cancer has a relatively poor prognosis with a low survival rate and drugs
      that target other cell death mechanism like autophagy may help improving current
      therapeutic strategy. This study investigated the anti-proliferative effect of
      Licarin A (LCA) from Myristica fragrans in non-small cell lung cancer cell lines
      A549, NCI-H23, NCI-H520 and NCI-H460. LCA inhibited proliferation of all the four
      cell lines in a dose and time dependent manner with minimum IC50 of 20.03 +/-
      3.12, 22.19 +/- 1.37 uM in NCI-H23 and A549 cells respectively. Hence NCI-H23 and
      A549 cells were used to assess the ability LCA to induce autophagy and apoptosis.
      LCA treatment caused G1 arrest, increase in Beclin 1, LC3II levels and
      degradation of p62 indicating activation of autophagy in both NCI-H23 and A549
      cells. In addition, LCA mediated apoptotic cell death was confirmed by MMP loss,
      increased ROS, cleaved PARP and decreased pro-caspase3. To understand the role of
      LCA induced autophagy and its association with apoptosis, cells were analysed
      following treatment with a late autophagy inhibitor-chloroquine and also after
      Beclin 1 siRNA transfection. Data indicated that inhibition of autophagy resulted
      in reduced anti-proliferative as well as pro-apoptotic ability of LCA. These
      findings confirmed that LCA brought about autophagy dependent apoptosis in non
      small cell lung cancer cells and hence it may serve as a potential drug candidate
      for non-small cell lung cancer therapy.

PMID- 29468482
TI  - Epirubicin induces apoptosis in osteoblasts through death-receptor and
      mitochondrial pathways.
AB  - Epirubicin is an anthracycline and is widely used in tumor treatment, but has
      toxic and undesirable side effects on wide range of cells and hematopoietic stem
      cells (HSC). Osteoblasts play important roles in bone development and in
      supporting HSC differentiation and maturation. It remains unknown whether
      epirubicin-induced bone loss and hematological toxicity are associated with its
      effect on osteoblasts. In primary osteoblast cell cultures, epirubicin inhibited
      cell growth and decreased mineralization. Moreover, epirubicin arrested
      osteoblasts in the G2/M phase, and this arrest was followed by apoptosis in which
      both the extrinsic (death receptor-mediated) and intrinsic (mitochondrial
      mediated) apoptotic pathways were evoked. The factors involved in the extrinsic
      apoptotic pathway were increased FasL and FADD as well as activated caspase-8.
      Those involved in the intrinsic apoptotic pathway were decreased Bcl-2; increased
      reactive oxygen species, Bax, cytochrome c; and activated caspase-9 and caspase
      3. These results demonstrate that epirubicin induced osteoblast apoptosis through
      the extrinsic and intrinsic apoptotic pathways, leading to the destruction of
      osteoblasts and consequent lessening of their functions in maintaining bone
      density and supporting hematopoietic stem cell differentiation and maturation.

PMID- 29468483
TI  - Elimination of Bimodal Size in InAs/GaAs Quantum Dots for Preparation of 1.3-MUm
      Quantum Dot Lasers.
AB  - The device characteristics of semiconductor quantum dot lasers have been improved
      with progress in active layer structures. Self-assembly formed InAs quantum dots
      grown on GaAs had been intensively promoted in order to achieve quantum dot
      lasers with superior device performances. In the process of growing high-density
      InAs/GaAs quantum dots, bimodal size occurs due to large mismatch and other
      factors. The bimodal size in the InAs/GaAs quantum dot system is eliminated by
      the method of high-temperature annealing and optimized the in situ annealing
      temperature. The annealing temperature is taken as the key optimization
      parameters, and the optimal annealing temperature of 680  degrees C was obtained.
      In this process, quantum dot growth temperature, InAs deposition, and arsenic
      (As) pressure are optimized to improve quantum dot quality and emission
      wavelength. A 1.3-MUm high-performance F-P quantum dot laser with a threshold
      current density of 110 A/cm2 was demonstrated.

PMID- 29468484
TI  - Seek and you shall find... multiple truths.

PMID- 29468485
TI  - Characterization of a novel breast cancer cell line derived from a metastatic
      bone lesion of a breast cancer patient.
AB  - PURPOSE: We aimed to generate and characterize a novel cell line from a breast
      cancer bone metastasis to better study the progression of the disease. METHODS:
      The cell line, P7731, was derived from a metastatic bone lesion of a breast
      cancer patient and assessed for marker expression. P7731 was analyzed for DNA
      copy number variation, somatic mutations, and gene expression and was compared
      with the primary tumor. RESULTS: P7731 cells are negative for estrogen receptor
      alpha (ERalpha), progesterone receptor (PR), and HER2 (triple-negative); strongly
      express vimentin (100% of cells positive) and also express cytokeratins 8/18 and
      19 but at lower frequencies. Flow cytometry indicates P7731 cells are
      predominantly CD44+/CD49f+/EpCAM-, consistent with a primitive, mesenchymal-like
      phenotype. The cell line is tumorigenic in immunocompromised mice. Exome
      sequencing identified a total of 45 and 76 somatic mutations in the primary tumor
      and cell line, respectively, of which 32 were identified in both samples and
      included mutations in known driver genes PIK3CA, TP53, and ARID1A. P7731 retains
      the DNA copy number alterations present in the matching primary tumor. Homozygous
      deletions detected in the cell line and in the primary tumor were found in
      regions containing three known (CDKN2A, CDKN2B, and CDKN1B) and 23 putative tumor
      suppressor genes. Cell line-specific gene amplification coupled with mRNA
      expression analysis revealed genes and pathways with potential pro-metastatic
      functions. CONCLUSION: This novel human breast cancer-bone metastasis cell line
      will be a useful model to study aspects of breast cancer biology, particularly
      metastasis-related changes from breast to bone.

PMID- 29468486
TI  - Tumor-associated macrophages and crown-like structures in adipose tissue in
      breast cancer.
AB  - PURPOSE: We aimed to evaluate macrophage infiltration and to identify the status
      of crown-like structures (CLSs) in mammary adipose tissue of human breast tissue
      in cases with and without breast cancer. METHODS: Breast adipose tissue was
      obtained from reduction mammoplasty (N = 56, Group 1), non-neoplastic breast
      tissue of breast cancer patients (N = 84, Group 2), and breast cancer with
      adipose stroma (N = 140, Group 3). Immunohistochemical staining of CD68 and CD163
      was performed, and the infiltrating macrophages and CLSs within breast adipose
      tissue were evaluated. RESULTS: Group 3 had the largest number of CD68-positive
      (CD68+) and CD163-positive (CD163+) macrophages and CLSs within adipose tissue (P
      < 0.001). Among Group 3, cases with high levels of CD68+ and CD163+ macrophages
      commonly had a higher histologic grade (P = 0.016 and P = 0.045), and cases with
      CD163+ CLSs were correlated with old age (P = 0.042), estrogen receptor
      negativity (P = 0.013), human epidermal growth factor receptor-2 positivity (P =
      0.043), and non-luminal A type (P = 0.039). Upon univariate analysis, high levels
      of CD163+ macrophages were associated with shorter disease-free survival in node
      negative breast cancer patients (P = 0.033), and CD68+ CLSs were associated with
      shorter overall survival in node-positive breast cancer patients (P = 0.015).
      CONCLUSIONS: CD68+ and/or CD163+ tumor-associated macrophage infiltration as well
      as CLSs are present in adipose tissue nearby the breast cancer lesion, and are
      associated with various clinicopathologic parameters of breast cancer.

PMID- 29468487
TI  - 68Ga-DOTATATE PET-CT imaging in carotid body paragangliomas.
AB  - OBJECTIVE: The aim of this study was to present our experience in the baseline
      evaluation of carotid body paragangliomas (CBP) with 68Ga-DOTATATE PET-CT.
      METHODS: Five patients (4F, 1M; age 24-73 years) with CBPs who underwent 68Ga
      DOTATATE PET-CT scan before the treatment were evaluated retrospectively. PET-CT
      images were analyzed visually as well as semiquantitatively, with measurement of
      maximum standardized uptake value (SUVmax). RESULTS: All patients had unilateral
      CBP lesion, showed intense 68Ga-DOTATATE uptake in PET-CT. Additionally, 68Ga
      DOTATATE avid lesions were found in two patients. One of them had focal intense
      uptake in thyroid gland and frontal cerebrum. The other one had intense uptake in
      bone and adrenal mass. Four patients were operated for unilateral primary CBP.
      Last patient was treated with peptide receptor radionuclide therapy (177Lu
      DOTATATE) for both metastatic pheochromocytoma and CBP. CONCLUSIONS: 68Ga
      DOTATATE PET-CT is a valuable imaging modality for staging of CBPs, detecting
      unknown lesions and changing the management of patients. It is also useful in
      demonstrating expression of SSTRs for PRRT opportunity.

PMID- 29468489
TI  - 2018 Letter from the Editor in Chief.

PMID- 29468488
TI  - TV viewing and incident venous thromboembolism: the Atherosclerotic Risk in
      Communities Study.
AB  - TV viewing is associated with risk of arterial vascular diseases, but has not
      been evaluated in relation to venous thromboembolism (VTE) risk in Western
      populations. In 1987-1989, the Atherosclerosis Risk in Communities Study obtained
      information on the frequency of TV viewing in participants aged 45-64 and
      followed them prospectively. In individuals free of prebaseline VTE (n = 15,
      158), we used a Cox proportional hazards models to estimate hazard ratios (HRs)
      and 95% confidence intervals (CIs) of incident VTE according to frequency of TV
      viewing ("Never or seldom", "Sometimes", "Often" or "Very often"). During the
      299,767 person-years of follow-up, we identified 691 VTE events. In a
      multivariable-adjusted model, the frequency of TV viewing showed a positive dose
      response relation with VTE incidence (P for trend = 0.036), in which "very often"
      viewing TV carried 1.71 (95% CI 1.26-2.32) times the risk of VTE compared with
      "never or seldom" viewing TV. This association to some degree was mediated by
      obesity (25% mediation, 95% CI 10.7-27.5). Even among individuals who met a
      recommended level of physical activity, viewing TV "very often" carried 1.80
      (1.04-3.09) times the risk of VTE, compared to viewing TV "never or seldom".
      Greater frequency of TV viewing was independently associated with increased risk
      of VTE, partially mediated by obesity. Achieving a recommended physical activity
      level did not eliminate the increased VTE risk associated with frequent TV
      viewing. Avoiding frequent TV viewing as well as increasing physical activity and
      controlling body weight might be beneficial for VTE prevention.

PMID- 29468491
TI  - Prenatal diagnosis of mediastinal neurenteric cyst: a case report and review of
      the literature.
AB  - Neurenteric cyst is a very rare developmental anomaly. Prenatal diagnosis of
      mediastinal neurenteric cysts has been reported rarely. We present a case of
      neurenteric cyst associated with vertebral anomalies diagnosed by prenatal
      ultrasonography at 31 weeks of gestation, which was treated successfully in the
      early neonatal period. In addition, we searched the English literature for all
      cases of mediastinal neurenteric cyst diagnosed in the prenatal period reported
      to date. We found that only 17 cases were reported previously. We reviewed the
      reports of these 17 patients along with our case, and we investigated the
      prenatal and postnatal diagnosis and treatment approaches and the factors
      influencing the prognosis. Fetuses with mediastinal neurenteric cysts should be
      monitored regularly by ultrasonography. Fetuses with no signs of hydrops are more
      likely to survive with proper neonatal center transfer, regular follow-up, and
      appropriate postnatal approach. Fetuses with hydrops findings have a high risk of
      fetal and neonatal death.

PMID- 29468490
TI  - Negative pressure wound therapy reduces the motility of Pseudomonas aeruginosa
      and enhances wound healing in a rabbit ear biofilm infection model.
AB  - Pseudomonas aeruginosa motility, virulence factors and biofilms are known to be
      detrimental to wound healing. The efficacy of negative pressure wound therapy
      (NPWT) against P. aeruginosa has been little studied, either in vitro or in vivo.
      The present study evaluated the effect of negative pressure (NP) on P. aeruginosa
      motility in vitro, and the effect of NPWT on virulence factors and biofilms in
      vivo. P. aeruginosa motility was quantified under different levels of NP
      (atmospheric pressure, - 75, - 125, - 200 mmHg) using an in vitro model.
      Swimming, swarming and twitching motility were significantly inhibited by NP (-
      125 and - 200 mmHg) compared with atmospheric pressure (p = 0.05). Virulence
      factors and biofilm components were quantified in NPWT and gauze treated groups
      using a rabbit ear biofilm model. Biofilm structure was studied with fluorescence
      microscopy and scanning electron microscopy. Additionally, viable bacterial
      counts and histological wound healing parameters were measured. Compared with the
      control, NPWT treatment resulted in a significant reduction in expression of all
      virulence factors assayed including exotoxin A, rhamnolipid and elastase (p =
      0.01). A significant reduction of biofilm components (eDNA) (p = 0.01) was also
      observed in the NPWT group. The reduction of biofilm matrix was verified by
      fluorescence- and scanning electron-microscopy. NPWT lead to better histologic
      parameters (p = 0.01) and decreased bacterial counts (p = 0.05) compared with the
      control. NPWT treatment was demonstrated to be an effective strategy to reduce
      virulence factors and biofilm components, which may explain the increased wound
      healing observed.

PMID- 29468492
TI  - Exchange Sex Among Persons Who Inject Drugs in the New York Metropolitan Area:
      The Importance of Local Context, Gender and Sexual Identity.
AB  - Exchanging sex for money or drugs is known to increase risk for HIV among persons
      who inject drugs (PWID). To better understand determinants of exchange sex among
      PWID we examined factors associated with exchange sex in the New York
      metropolitan area-defined as New York City (NYC), NY; Newark, NJ; and Long
      Island, NY-using data from the 2012 National HIV Behavioral Surveillance system
      cycle on injection drug use. Of the 1160 PWID in this analysis, 24% reported
      exchange sex, with differences in gender and sexual identity by location. In
      multivariable analysis gay/bisexual men, heterosexual women, and lesbian, gay, or
      bisexual (LGB) women were more likely to exchange sex compared to heterosexual
      men. Exchange sex was also associated with race/ethnicity, homelessness,
      incarceration, location, and non-injection crack and cocaine use. We find that
      heterosexual women and LGB women who injected drugs residing in Newark were more
      likely to report exchange sex compared to NYC. This study highlights how local
      conditions impact exchange sex.

PMID- 29468494
TI  - Census Tract Poverty and Racial Disparities in HIV Rates in Milwaukee County,
      Wisconsin, 2009-2014.
AB  - Previous work has documented associations between poverty and HIV. Understanding
      of these relationships at local levels could help target prevention efforts;
      however, HIV surveillance systems do not capture individual-level poverty
      measures. We utilized the Public Health Disparities Geocoding Project methods to
      examine HIV rates by census tract poverty. HIV rates and rate ratios were
      computed by census tract poverty (< 5.0, 5.0-9.9, 10.0-19.9, > 20.0% of
      individual below the federal poverty level) for all races and stratified by Black
      and White race using Poisson regression. We observed higher HIV rates in the
      highest poverty gradient compared to the lowest poverty gradient for all races
      combined and among White cases. After adjustment, HIV rates were similar across
      poverty gradients for all comparisons. Our findings suggest that the association
      between poverty and HIV may differ by subpopulation, while demonstrating the
      potential for HIV prevention targeting residents of high poverty areas.

PMID- 29468495
TI  - Alertness and cognitive control: Toward a spatial grouping hypothesis.
AB  - A puzzling interaction involving alertness and cognitive control is indicated by
      the finding of faster performance but larger congruency effects on alert trials
      (on which alerting cues are presented before the task stimuli) than on no-alert
      trials in selective attention tasks. In the present study, the author conducted
      four experiments to test hypotheses about the interaction. Manipulation of
      stimulus spacing revealed a difference in congruency effects between alert and no
      alert trials for narrowly spaced stimuli but not for widely spaced stimuli,
      inconsistent with the hypothesis that increased alertness is associated with more
      diffuse attention. Manipulation of color grouping revealed similar differences in
      congruency effects between alert and no-alert trials for same-color and different
      color groupings of targets and distractors, inconsistent with the general
      hypothesis that increased alertness is associated with more perceptual grouping.
      To explain the results, the author proposes that increased alertness is
      associated specifically with more spatial grouping of stimuli, possibly by
      modulating the threshold for parsing stimulus displays into distinct objects.

PMID- 29468493
TI  - Facilitators and Barriers to Pre-Exposure Prophylaxis (PrEP) Use Among Black
      Individuals in the United States: Results from the National Survey on HIV in the
      Black Community (NSHBC).
AB  - This study explores willingness to use PrEP among Black individuals in the US.
      From February to April 2016, an online survey was administered to a nationally
      representative sample of Black individuals. 855 individuals who were HIV negative
      by self-report participated [mean age: 33.6 (SD 9.2); 45.5% male]. Among all
      respondents, 14.5% were aware of, and 26.0% would be willing to use PrEP. Among
      high-risk individuals (N = 327), 19.8% knew about and 35.1% would be willing to
      use PrEP. The most common reason for lack of willingness among high-risk
      individuals was low self-perceived risk (65.1%). In multivariate analysis,
      individuals reporting single marital status [OR 1.8 (1.2, 2.5), p = 0.002],
      depressive symptoms [OR 1.6 (1.2, 2.2), p = 0.0054], arrest history [OR 1.7(1.2,
      2.4), p = 0.0003], PrEP knowledge [OR 1.5 (1.0, 2.3), p = 0.0247] and belief in
      HIV conspiracies [OR 1.3 (1.1, 1.5), p = 0.0075] were more willing to use PrEP.
      Participants who saw a health care provider less frequently were less willing to
      use PrEP [OR 0.5 (0.4, 0.8), p = 0.0044]. Among a nationally representative
      sample of Black individuals, few high risk individuals were willing to use PrEP.
      Interventions to increase risk awareness, PrEP knowledge and access to care are
      necessary to improve PrEP uptake.

PMID- 29468496
TI  - Assessing the role of accuracy-based feedback in value-driven attentional
      capture.
AB  - Despite being physically nonsalient and task-irrelevant, objects rendered in a
      color that once signaled monetary reward reflexively capture attention during
      visual search, a phenomenon known as value-driven attentional capture (VDAC).
      However, it remains a subject of empirical controversy whether learned reward
      associations are necessary to driving subsequent attentional capture: VDAC-like
      effects have been observed when accuracy-based feedback alone was used during the
      VDAC training phase, resulting in attentional capture by objects that were never
      associated with monetary reward; perplexingly, the presence of these VDAC-like
      effects in the literature conflicts with those of a number of control studies in
      which no such capture has been observed, leaving the issue currently unresolved.
      In this Registered Report, we present new empirical evidence of attentional
      capture by unrewarded former targets following limited accuracy-based training.
      We proposed to replicate these results in an independent sample and to test an
      empirically derived hypothesis concerning a methodological difference between the
      studies that have shown VDAC-like effects with accuracy-based feedback and those
      that have not. In short, we found no evidence that this methodological difference
      accounts for the inconsistencies in the literature, but our replication efforts
      were overwhelmingly successful, thus reinvigorating debate about the role that
      selection history may play in value-driven attentional capture.

PMID- 29468497
TI  - Effectiveness of Integrating Simulation with Art-Based Teaching Strategies on
      Oncology Fellows' Performance Regarding Breaking Bad News.
AB  - The task of breaking bad news (BBN) may be improved by incorporating simulation
      with art-based teaching methods. The aim of the present study was to assess the
      effect of an integrating simulation with art-based teaching strategies, on
      fellows' performance regarding BBN, in Iran. The study was carried out using
      quasi-experimental methods, interrupted time series. The participants were
      selected from medical oncology fellows at two teaching hospitals of Tehran
      University of Medical Sciences (TUMS), Iran. Participants were trained through
      workshop, followed by engaging participants with different types of art-based
      teaching methods. In order to assess the effectiveness of the integrating model,
      fellows' performance was rated by two independent raters (standardized patients
      (SPs) and faculty members) using the BBN assessment checklist. This assessment
      tool measured seven different domains of BBN skill. Segmented regression was used
      to analyze the results of study. Performance of all oncology fellows (n = 19) was
      assessed for 228 time points during the study, by rating three time points before
      and three time points after the intervention by two raters. Based on SP ratings,
      fellows' performance scores in post-training showed significant level changes in
      three domains of BBN checklist (B = 1.126, F = 3.221, G = 2.241; p < 0.05).
      Similarly, the significant level change in fellows' score rated by faculty
      members in post-training was B = 1.091, F = 3.273, G = 1.724; p < 0.05. There was
      no significant change in trend of fellows' performance after the intervention.
      Our results showed that using an integrating simulation with art-based teaching
      strategies may help oncology fellows to improve their communication skills in
      different facets of BBN performance. Iranian Registry of Clinical Trials ID:
      IRCT2016011626039N1.

PMID- 29468499
TI  - Resveratrol Improves Neuroimmune Dysregulation Through the Inhibition of Neuronal
      Toll-Like Receptors and COX-2 Signaling in BTBR T+ Itpr3tf/J Mice.
AB  - Autism is a neurodevelopmental disorder characterized by deficits in qualitative
      impairments in communication, repetitive and social interaction, restricted, and
      stereotyped patterns of behavior. Resveratrol has been extensively studied
      pharmacologically and biologically and has anti-inflammatory, antioxidant, and
      neuroprotective effects on neuronal damage in neurodegenerative disorders. The
      BTBR T+ Itpr3tf/J (BTBR) autistic mouse model has been explored for treatment of
      autism, which shows low reciprocal social interactions, impaired juvenile play,
      and decreased social approach. Here, we explored whether resveratrol treatment
      decreases neuroimmune dysregulation mediated through toll-like receptor (TLR4)
      and nuclear factor-kappaB (NF-kappaB) signaling pathway in BTBR mice. We
      investigated the effect of resveratrol treatment on TLR2, TLR3, TLR4, NF-kappaB,
      and inducible nitric oxide synthase (iNOS or NOS2) levels in CD4 spleen cells. We
      also assessed the effect of resveratrol treatment on TLR2, TLR3, TLR4, NF-kappaB,
      iNOS, and cyclooxygenase (COX-2) mRNA expression levels in the brain tissue. We
      further explored TLR2, TLR4, NF-kappaB, iNOS, and COX-2 protein expression levels
      in the brain tissue. Resveratrol treatment on BTBR mice significantly decreased
      CD4+TLR2+, CD4+TLR3+, CD4+TLR4+ CD4+NF-kappaB+, and CD4+iNOS+ levels in spleen
      cells. Resveratrol treatment on BTBR mice decreased TLR2, TLR3, TLR4, NF-kappaB,
      iNOS, and COX-2 mRNA expression levels in brain tissue. Moreover, resveratrol
      treatment resulted in decreased protein expression of TLR2, TLR3, TLR4, NF
      kappaB, iNOS, and COX-2 in brain tissue. Taken together, these results indicate
      that resveratrol treatment improves neuroimmune dysregulation through the
      inhibition of proinflammatory mediators and TLRs/NF-kappaB transcription factor
      signaling, which might be help devise future therapies for neuroimmune disorders.

PMID- 29468500
TI  - SIMS of Organic Materials-Interface Location in Argon Gas Cluster Depth Profiles
      Using Negative Secondary Ions.
AB  - A procedure has been established to define the interface position in depth
      profiles accurately when using secondary ion mass spectrometry and the negative
      secondary ions. The interface position varies strongly with the extent of the
      matrix effect and so depends on the secondary ion measured. Intensity profiles
      have been measured at both fluorenylmethyloxycarbonyl-L-pentafluorophenylalanine
      (FMOC) to Irganox 1010 and Irganox 1010 to FMOC interfaces for many secondary
      ions. These profiles show separations of the two interfaces that vary over some
      10 nm depending on the secondary ion selected. The shapes of these profiles are
      strongly governed by matrix effects, slightly weakened by a long wavelength
      roughening. The matrix effects are separately measured using homogeneous, known
      mixtures of these two materials. Removal of the matrix and roughening effects
      give consistent compositional profiles for all ions that are described by an
      integrated exponentially modified Gaussian (EMG) profile. Use of a simple
      integrated Gaussian may lead to significant errors. The average interface
      positions in the compositional profiles are determined to standard uncertainties
      of 0.19 and 0.14 nm, respectively, using the integrated EMG function.
      Alternatively, and more simply, it is shown that interface positions and profiles
      may be deduced from data for several secondary ions with measured matrix factors
      by simply extrapolating the result to Xi = 0. Care must be taken in quoting
      interface resolutions since those measured for predominantly Gaussian interfaces
      with Xi above or below zero, without correction, appear significantly better than
      the true resolution. Graphical Abstract ?.

PMID- 29468501
TI  - Resolution and Assignment of Differential Ion Mobility Spectra of Sarcosine and
      Isomers.
AB  - Due to their central role in biochemical processes, fast separation and
      identification of amino acids (AA) is of importance in many areas of the
      biomedical field including the diagnosis and monitoring of inborn errors of
      metabolism and biomarker discovery. Due to the large number of AA together with
      their isomers and isobars, common methods of AA analysis are tedious and time
      consuming because they include a chromatographic separation step requiring pre-
      or post-column derivatization. Here, we propose a rapid method of separation and
      identification of sarcosine, a biomarker candidate of prostate cancer, from
      isomers using differential ion mobility spectrometry (DIMS) interfaced with a
      tandem mass spectrometer (MS/MS) instrument. Baseline separation of protonated
      sarcosine from alpha- and beta-alanine isomers can be easily achieved.
      Identification of DIMS peak is performed using an isomer-specific activation mode
      where DIMS- and mass-selected ions are irradiated at selected wavenumbers
      allowing for the specific fragmentation via an infrared multiple photon
      dissociation (IRMPD) process. Two orthogonal methods to MS/MS are thus added,
      where the MS/MS(IRMPD) is nothing but an isomer-specific multiple reaction
      monitoring (MRM) method. The identification relies on the comparison of DIMS
      MS/MS(IRMPD) chromatograms recorded at different wavenumbers. Based on the
      comparison of IR spectra of the three isomers, it is shown that specific
      depletion of the two protonated alpha- and beta-alanine can be achieved, thus
      allowing for clear identification of the sarcosine peak. It is also demonstrated
      that DIMS-MS/MS(IRMPD) spectra in the carboxylic C=O stretching region allow for
      the resolution of overlapping DIMS peaks. Graphical Abstract ?.

PMID- 29468502
TI  - Gas Flow and Ion Transfer in Heated ESI Capillary Interfaces.
AB  - Transfer capillaries are the preferred means to transport ions, generated by
      electrospray ionization, from ambient conditions to vacuum. During the transfer
      of ions through the narrow, long tubes into vacuum, substantial losses are
      typical. However, recently it was demonstrated that these losses can be avoided
      altogether. To understand the experimental observation and provide a general
      model for the ion transport, here, we investigate the ion transport through
      capillaries by numerical simulation of interacting ions. The simulation
      encompasses all relevant factors, such as space charge, diffusion, gas flow, and
      heating. Special attention is paid to the influence of the gas flow on the
      transmission and especially the change imposed by heating. The gas flow is
      modeled by a one-dimensional gas dynamics description. A large number of ions are
      treated as point particles in this gas flow. This allows to investigate the
      influence of the capillary heating on the gas flow and by this on the ion
      transport. The results are compared with experimental findings. Graphical
      Abstract ?.

PMID- 29468503
TI  - Abnormal lipid metabolism in a rat model of arthritis: one possible pathway.
AB  - Collagen-induced arthritis (CIA) animal model is associated with systemic
      manifestations, including alteration of lipid metabolism. In the present study,
      one possible pathway of altered lipid metabolism is proposed. Specimens of joint
      tissue and plasma were collected from the CIA and control rats, and quantitative
      analysis of lipid components was performed by nuclear magnetic resonance (NMR)
      spectroscopy technique. Correlation analysis was performed between the level of
      lipid components and antioxidant enzymes, lactate dehydrogenase (LDH), lipid
      peroxidation (LP), and cytokines in joint tissue and plasma. Differentiation
      between the CIA and control rats was established on the basis of the quantity of
      lipid components in the joint tissue and plasma. Positive correlation was
      observed for all the enzymes vs. lipid components as well as LP vs. lipid
      components in plasma and joint tissue. Positive correlation was observed for
      enzymes in plasma and joint tissue. A negative correlation was observed in
      between the plasma and joint tissue with the level of lipid components. Cytokine
      levels were also correlated with the level of lipid components and ratios of
      saturated fatty acids/unsaturated fatty acids in plasma and joint tissue.
      Inflammatory disease activity in CIA rats with synovitis brought about a
      significant change in lipid metabolism. Taken together, the results of our study
      are delineating a possible pathway of altered lipid metabolism in the CIA rat
      model, thereby contributing further to an understanding of the pathophysiology of
      rheumatoid arthritis (RA).

PMID- 29468504
TI  - MCAM knockdown impairs PPARgamma expression and 3T3-L1 fibroblasts
      differentiation to adipocytes.
AB  - We investigated for the first time the expression of melanoma cell adhesion
      molecule (MCAM) and its involvement in the differentiation of 3T3-L1 fibroblasts
      to adipocytes. We found that MCAM mRNA increased subsequent to the activation of
      the master regulator of adipogenesis, PPARgamma, and this increase was maintained
      in the mature adipocytes. On the other hand, MCAM knockdown impaired
      differentiation and induction of PPARgamma as well as expression of genes
      activated by PPARgamma. However, events that precede and are necessary for early
      PPARgamma activation, such as C/EBPbeta induction, beta-catenin downregulation,
      and ERK activation, were not affected in the MCAM knockdown cells. In keeping
      with this, the increase in PPARgamma mRNA that precedes MCAM induction was not
      altered in the knockdown cells. In conclusion, our findings suggest that MCAM is
      a gene upregulated and involved in maintaining PPARgamma induction in the late
      but not in the early stages of 3T3-L1 fibroblasts adipogenesis.

PMID- 29468505
TI  - A Cross-Cultural Perspective on the Relationships between Emotional Separation,
      Parental Trust, and Identity in Adolescents.
AB  - Emotional separation and parental trust in parent-adolescent relationships are
      important factors for adolescent identity formation. However, prior research
      findings on emotional separation are inconsistent. This study aimed to conduct a
      more rigorous examination of the associations of emotional separation and
      parental trust with identity synthesis, confusion, and consolidation by applying
      a bi-factor model to identity, using adolescent samples from Lithuania (N = 610;
      53.9% female; M age  = 14.92), Italy (N = 411; 57.4% female; M age  = 15.03), and
      Japan (N = 759; 43.7% female; M age  = 14.13). Structural equation modeling
      revealed that emotional separation and parental trust were consistently
      associated with identity consolidation across the three countries, rather than
      associated with identity synthesis and identity confusion. Furthermore, the
      patterns of associations of emotional separation and parental trust with identity
      synthesis and identity confusion differed across the three nations. Overall, this
      study provides a better understanding of the role of emotional separation and
      parental trust in adolescent identity formation by suggesting the importance of
      the identity consolidation in the association between parent-child relationships
      and identity formation across three countries.

PMID- 29468506
TI  - Dimensions of Short-Term and Long-Term Self-Regulation in Adolescence:
      Associations with Maternal and Paternal Parenting and Parent-Child Relationship
      Quality.
AB  - Relatively little is known about the degree to which subcomponents of self
      regulation change during early to middle adolescence. This study considered
      familial predictors (maternal/paternal regulatory support, antagonistic
      parenting, and parent-child closeness) of rank-order change in behavioral,
      emotional and cognitive regulation and perseverance over one year. N = 452
      adolescents ages 11-16 years and their parents completed questionnaires and
      parent-child discussion tasks (48.7% male; 69.6% white). Results indicated
      minimal direct effects of parenting, though maternal and paternal parenting and
      parent-child closeness exerted small effects that were moderated by prior levels
      of cognitive regulation and perseverance. Parents may contribute to the
      development of complex regulatory capacities that mature after foundational
      emotional and behavioral regulation competencies.

PMID- 29468507
TI  - Impact of clinical factors and UGT1A9 and CYP2B6 genotype on inter-individual
      differences in propofol pharmacokinetics.
AB  - PURPOSE: Propofol is one of the most widely used fast-acting intravenously
      administered anesthetics. However, although large inter-individual differences in
      dose requirements and recovery time have been observed, there are few previous
      studies in which the association between several potential covariates, including
      genetic factors such as the UGT1A9 and CYP2B6 genotypes, and propofol
      pharmacokinetics was simultaneously examined. This study aimed to identify
      factors determining propofol pharmacokinetics. METHODS: Eighty-three patients
      were enrolled, and their blood samples were collected 1, 5, 10, and 15 min after
      administering a single intravenous bolus of propofol at a dose of 2.0 ml/kg to
      measure propofol plasma concentration. Area under the time-plasma concentration
      curve from zero up to the last measurable time point (AUC15min) was determined
      from the concentration data. The inter-individual variability of the propofol
      pharmacokinetics was evaluated by investigating relationships between AUC15min
      and genotype of UGT1A9 and CYP2B6; clinical factors, such as age, sex, body mass
      index (BMI), and preoperative hematological examination; and hemodynamic
      variables measured by a pulse dye densitogram analyzer. The Spearman rank
      correlation coefficient and the Mann-Whitney U test were used for the statistical
      analysis of continuous and categorical values, respectively. Subsequently,
      clinical factors that had p values of < 0.05 in the univariate analysis were
      examined in a multivariate analysis using multiple linear regression analysis.
      RESULTS: Age, BMI, indocyanine green disappearance ratio (K-ICG), hepatic blood
      flow (HBF), preoperative hemoglobin level, and sex were correlated with AUC15min
      (p < 0.05) in univariate analysis. Multivariate analysis performed to adjust for
      age, BMI, K-ICG, HBF, preoperative hemoglobin level, and sex revealed only BMI as
      an independent factor associated with AUC15min. CONCLUSIONS: This study
      demonstrated that BMI influences propofol pharmacokinetics after its
      administration as a single intravenous injection, while UGT1A9 and CYP2B6 SNPs,
      other clinical factors, and hemodynamic variables do not. These results suggest
      that BMI is an independent factor associated with propofol pharmacokinetics in
      several potential covariates. CLINICAL TRIALS REGISTRATION NUMBER: University
      Hospital Medical Information Network (UMIN000022948).

PMID- 29468509
TI  - [Update on colon cancer 2017].

PMID- 29468508
TI  - Ultrasound-guided bilateral superficial cervical block and preemptive single-dose
      oral tizanidine for post-thyroidectomy pain: a randomized-controlled double-blind
      study.
AB  - PURPOSES: The postoperative analgesic effect of tizanidine has not yet been
      evaluated sufficiently. The role of bilateral superficial cervical plexus block
      (BSCPB) for postoperative analgesia after thyroidectomy remains questionable. We
      aimed to evaluate the analgesic effect of combined use of BSCPB and a single-dose
      oral tizanidine in patients undergoing elective thyroid surgery. METHODS: Sixty
      patients undergoing thyroidectomy were randomized into 3 groups. The control
      group (Group C, n = 20) received BSCPB with 0.9% saline plus oral placebo. The
      superficial cervical group (Group SC, n = 20) received BSCPB with 0.25%
      bupivacaine plus oral placebo. The superficial cervical and tizanidine group
      (Group SC + T, n = 20) received BSCPB with 0.25% bupivacaine plus tizanidine 6 mg
      capsule. Surgical site pain scores, opioid consumption, rescue analgesia,
      posterior neck pain, headache, and opioid-related side effects were assessed for
      the first 24 h. RESULTS: Compared with Group C, rest and swallowing pain scores
      in Group SC and Group SC + T were statistically lower at all postoperative time
      points (p < 0.05). Fentanyl consumption was lower in Group SC and Group SC + T
      than in Group C at time periods 0-4 and 4-8 h (p < 0.05). Fentanyl consumption
      was lower in Group SC + T than in Group SC at 0-4 h (p = 0.006). Total fentanyl
      consumption was higher in Group C than in the other groups (p < 0.001).
      Postoperative cervical pain and occipital headache were significantly lower in
      Group SC + T than in the other groups (p < 0.05). CONCLUSIONS: Ultrasound-guided
      BSCPB with or without preemptive oral tizanidine was effective at reducing
      postoperative pain and opioid consumption in patients undergoing total
      thyroidectomy. Addition of preemptive oral tizanidine to BSCPB reduced the early
      postoperative opioid consumption, posterior neck pain, and occipital headache.
      CLINICAL TRIALS REGISTRY: The study was registered with a clinical trials
      registry (ClinicalTrials.gov. identifier NCT02725359).

PMID- 29468510
TI  - [Help for self-help for patients with chronic pain].

PMID- 29468511
TI  - [Suprascapular nerve entrapment].

PMID- 29468512
TI  - [Schistosomiasis].

PMID- 29468513
TI  - [Total ankle replacement].

PMID- 29468514
TI  - [Cartilage repair therapies of the talus].

PMID- 29468515
TI  - [Lateral instability of the ankle joint].

PMID- 29468517
TI  - Foreign-Born Blacks Experience Lower Odds of Obesity but Higher Odds of Diabetes
      than US-Born Blacks in New York City.
AB  - Research is limited on the health of foreign-born Blacks (FBBs), who are often
      grouped with African Americans. This study compared obesity and diabetes odds in
      FBBs and US-born Blacks (USBBs) in NYC. Analyzing the 2009-2013 NYC Community
      Health Survey (3701 FBBs and 6297 USBBs), weighted multivariate logistic
      regression examined odds of obesity and diabetes, adjusting for age, gender,
      education, income, marital status, children < 18, BMI (for diabetes only) and
      duration of residence. FBBs had lower odds of obesity [OR  0.62 (95% CI 0.54,
      0.72)] and greater odds of diabetes [OR 1.24 (95% CI 1.01, 1.52)] compared to
      USBBs. FBBs had 1.4 times the odds of diabetes at overweight status, compared to
      USBBs [OR  1.40 (95% CI 1.01, 1.95)]. Living in the US >= 10 years was not
      associated with odds of obesity and diabetes. Future research should seek to
      uncover unique risk profiles of sub-ethnic groups in the African diaspora.

PMID- 29468516
TI  - A Systematic Review of Cognition in Chiari I Malformation.
AB  - Displacement of the cerebellar tonsils in Chiari type I malformation (CMI) can
      affect functions controlled by the cerebellum and brainstem. While playing an
      integral role in the control of movement, the cerebellum also has widespread
      cortical connections, influencing a range of cognitive process. A systematic
      literature review was conducted to examine the relationship between cognition and
      CMI, assessing evidence for general or domain-specific cognitive change. The
      search protocol examined the AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE,
      PsycINFO, and Scopus databases. Articles meeting the following criteria were
      included in this review (i) examined children or adults with a clinically defined
      diagnosis of CMI, (ii) assessed cognitive function with a prospective
      examination, (iii) included at least one standardized instrument designed to
      measure general or specific domains of cognitive function, and (iv) were
      published in English in a peer-reviewed journal. Twelve articles were identified,
      including 783 cases aged 3 months to 64 years. General cognition, processing
      speed, and learning and memory appeared less affected, while language deficits
      appeared to diminish with age. Executive dysfunction was the most commonly
      reported cognitive impairment, while attention and working memory, and
      visuospatial and perceptual skills also appeared vulnerable. Numerous
      methodological limitations were identified that should be considered in
      interpreting the impact of CMI and planning future investigations. Overall, there
      is currently insufficient evidence to describe a valid and reliable profile of
      cognitive impairment in CMI. Further research is required to confirm these
      preliminary psychometric results and integrate them with pathophysiological
      models.

PMID- 29468518
TI  - Cultural Factors Influencing Osteoarthritis Care in Asian Communities: A Review
      of the Evidence.
AB  - With the prevalence of osteoarthritis (OA) increasing internationally, there is a
      need to study the impact of this disease on culturally diverse populations.
      Individuals of Asian descent make up more than 60% of the world population, yet
      comprehensive information on the cultural factors that impact OA care is not
      available. Scoping review methodology using directed content analysis was
      employed to identify and analyze existing research on OA care for Asians. A
      categorization matrix was developed using the six care areas from the OA clinical
      practice guidelines along with an additional three non-clinical areas (cross
      cultural adaptation of clinical tools; psychological well-being; family systems
      and informal care) identified in an initial scan resulting in a total of nine OA
      care areas to guide initial coding. A full scoping review was conducted across
      five databases resulting in 656 abstracts screened. All text was coded using the
      categorization matrix and resulting subthemes were identified. A total of 74
      articles were analyzed with 23 subthemes identified across the nine categories.
      Four new perspectives emerged to support OA care for Asian populations: (1) the
      importance of family and peer assistance, (2) the importance of culturally
      specific activities, (3) distrust in western medicine, and (4) impact of positive
      coping mechanisms on health appraisals. While Asians are more susceptible to knee
      and hand OA because of their cultural lifestyle factors (e.g. squatting for
      chores, hygiene and religious activities), and traditional beliefs on OA
      management (e.g. traditional diet, topical oils, physical therapy), many do not
      present themselves for conventional treatments (e.g. surgery) until all
      traditional treatments are exhausted. The results suggest that cultural factors
      influence the uptake of OA management practices among Asians. Greater awareness
      of these cultural factors may improve diagnosis, treatment, and management of OA
      among Asian patients.

PMID- 29468519
TI  - Effect of Pressure Support Ventilation on Carboxyhemoglobin Toxicokinetic after
      Acute Carbon Monoxide Intoxication: a Swine Model.
AB  - INTRODUCTION: In an experimental study on carbon monoxide (CO) exposure in swine,
      we aimed to compare the influence of oxygen therapy using a non-rebreathing mask
      (NRM) to continuous positive airway pressure (CPAP) and two pressure support
      ventilation (PSV) devices on the decrease of the terminal elimination half-life
      of carboxyhemoglobin (COHb t1/2). This was the primary outcome. METHODS: Eight
      spontaneously breathing pigs were sedated by propofol and exposed to 940 ppm CO
      several times (n = 25) to obtain COHb levels of 30%. CPAPb (high flow open
      system, CPAP Boussignac(r) [7.5 cmH2O]), PSV-Vy (open system, Vylife
      Boussignac(r)), and PSV-Leg (closed system, Legendair(r) [inspiratory/expiratory
      airway pressure 12/4 cmH2O]) devices were used in a randomized order and compared
      to NRM (O2 at 15 l min-1) and atmospheric air (AA). The primary outcome was COHb
      t1/2. Multiple comparisons were performed using Dunn's tests. RESULTS: Median
      FiO2 and minute ventilation were significantly higher in the PSV-Leg group than
      the NRM group (p < 0.05). Median COHb t1/2 was 251, 85, 82, 93, and 58 min for
      AA, NRM, CPAPb, PSV-Vy, and PSV-Leg, respectively. All the interventions were
      superior to AA in terms of CO elimination (p < 0.001), but there was no
      statistically significant difference between CPAP or PSV and NRM. There was only
      a trend between PSV-Leg and NRM (p = 0.18). The median AUCs for ln (COHb) * time
      (h) were 170, 79, 83, 100, and 64 for AA, NRM, CPAPb, PSV-Vy, and PSV-Leg
      respectively, with a statistically significant difference only between AA and PSV
      Leg (p = 0.002). CONCLUSION: In conclusion, in our study on CO intoxication in
      swine, the use of the closed PSV-Leg system led to the shortest COHb t1/2. These
      results suggest that PSV-Leg can be more efficient than NRM in eliminating CO and
      support the design of a clinical study to assess this hypothesis.

PMID- 29468520
TI  - Impact of Di-2-Ethylhexyl Phthalate Metabolites on Male Reproductive Function: a
      Systematic Review of Human Evidence.
AB  - PURPOSE OF REVIEW: The purpose of this review is to systematically review the
      literature linking di-2-ethylhexyl phthalate (DEHP) exposure with effects on
      reproductive health in adult males. RECENT FINDINGS: Thirty-three papers were
      included of which 28 were cross-sectional. Twenty-one papers investigated semen
      samples, 18 investigated reproductive hormones, and three studies investigated
      time to pregnancy. Studies revealed some but inconsistent indications that higher
      urinary DEHP metabolite levels are associated with an increase in the proportion
      of spermatozoa with damaged DNA and to a decrease in sperm concentration and
      motility. A negative association between DEHP metabolites and testosterone levels
      was more consistent. DEHP metabolites do not seem to be associated with a delay
      in time to pregnancy, but data are sparse. The studies on DEHP exposure and
      reproductive biomarkers in men converge to support the hypothesis that DEHP
      exposure is related to impaired male reproductive function. Longitudinal studies
      are needed to establish if the observed associations are causal.

PMID- 29468521
TI  - Identification of a Constitutively Active Mutant Mouse IRAK2 by Retroviral
      Expression Screening.
AB  - To identify the importance of IRAK2 kinase activity in TLR-mediated signaling
      pathways, we constructed a retroviral vector harboring either a mouse IRAK2 gene
      (IRAK2-WT) or with its mutant with loss of function of its ATP-binding site
      (IRAK2-KD). Further, we comparatively analyzed for the gain of function and
      modulations in TLR-mediated signaling pathways in IRAK2 knockout (IRAK2-KO)
      macrophages upon introduction of the IRAK2-WT retroviral constructs. The
      pBS/IRAK2-KD with the ATP-binding site mutation in IRAK2 was obtained by using
      site-specific mutagenesis. The recombinants were identified with appropriate
      double digestion and sequence analysis. The recombinant vector constructs were
      transfected by lipofection into phoenix packaging cells. The viral vectors (107
      cfu/mL) with the construct were allowed to infect IRAK2-KO macrophages. The
      results showed that IRAK2-WT gene overexpressed in the IRAK2-KO macrophages
      exhibited a modified IRAK2 expression upon LPS induction. However, the
      modification was absent with IRAK2-KD construct on LPS stimulation; instead, the
      IRAK2 protein stability was reduced considerably. The results further show that
      the LPS-induced effect on the stability of IRAK2 is dependent of IRAK4
      stimulation.

PMID- 29468522
TI  - Mechanism of evolution by genetic assimilation : Equivalence and independence of
      genetic mutation and epigenetic modulation in phenotypic expression.
AB  - Conrad H. Waddington discovered the phenomenon of genetic assimilation through a
      series of experiments on fruit flies. In those experiments, artificially exerted
      environmental stress induced plastic phenotypic changes in the fruit flies, but
      after some generations, the same phenotypic variant started to appear without the
      environmental stress. Both the initial state (where the phenotypic changes were
      environmentally induced and plastic) and the final state (where the phenotypic
      changes were genetically fixed and constitutive) are experimental facts. However,
      it remains unclear how the environmentally induced phenotypic change in the first
      generation becomes genetically fixed in the central process of genetic
      assimilation itself. We have argued that the key to understanding the mechanism
      of genetic assimilation lies in epigenetics, and proposed the "cooperative model"
      in which the evolutionary process depends on both genetic and epigenetic factors.
      Evolutionary simulations based on the cooperative model reproduced the process of
      genetic assimilation. Detailed analysis of the trajectories has revealed genetic
      assimilation is a process in which epigenetically induced phenotypic changes are
      incrementally and statistically replaced with multiple minor genetic mutations
      through natural selection. In this scenario, epigenetic and genetic changes may
      be considered as mutually independent but equivalent in terms of their effects on
      phenotypic changes. This finding rejects the common (and confused) hypothesis
      that epigenetically induced phenotypic changes depend on genetic mutations.
      Furthermore, we argue that transgenerational epigenetic inheritance is not
      required for evolution by genetic assimilation.

PMID- 29468523
TI  - Gender differential in social and economic predictors of incident major
      depressive disorder in the Ibadan Study of Ageing.
AB  - PURPOSE: Working on the hypothesis that the social and economic factors
      associated with onset of late-life depression operate differently for men and
      women, we investigated the impact of current social relationships and lifetime
      occupational attainment on incident major depressive disorder (MDD) assessed in
      three follow-up waves over a period of 5 years. METHODS: Participants were part
      of a household multistage probability sample of 2149 Nigerians who were aged 65
      years and above. The presence of current and lifetime MDD was assessed using the
      World Health Organization (WHO) Composite International Diagnostic Interview.
      Participants' highest occupational attainment was categorised based on the
      International Standard Classification of Occupations, while socio-economic
      positions were estimated using asset-based measures relevant to low-income
      settings. Current social contacts and participation were assessed using items
      from the WHO Disability Assessment Schedule. RESULTS: We found an incidence rate
      of 120.9 per 1000 persons years (95% CI = 110.4-132.5) among 1394 persons who
      were free of lifetime MDD and dementia at baseline. Incidence rates were 94.7
      (95% CI = 82.5-108.7) and 153.8 (136.3-173.6) per 1000 person years, in men and
      women respectively. In analyses comparing gender and adjusting for the effect of
      age, we found that while a lifetime of unskilled occupation (trade: HR = 1.4, 95%
      CI = 1.0-2.0, and elementary occupations: HR = 1.5, 95% CI = 1.1-2.1) was
      significantly associated with incident MDD in men (but not in women), living in a
      rural location (HR = 1.3, 95% CI = 1.0-1.7) and having no regular contact with
      family (HR = 2.2, 95% CI = 1.0-4.7) at baseline significantly predicted
      subsequent onset of MDD in women. CONCLUSION: There was a gender differential in
      the association of social and economic factors with incident MDD in this sample.
      These findings have implications for the design of early prevention strategies
      for late-life depression in sub-Saharan Africa.

PMID- 29468524
TI  - TAFRO syndrome with refractory thrombocytopenia responding to tocilizumab and
      romiplostim: a case report.
AB  - Thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly (TAFRO)
      syndrome is a unique clinicopathologic subtype of multicentric Castleman's
      disease that has recently been identified in Japan. However, little is known
      about its renal histological changes and the optimal treatment for TAFRO
      syndrome. An 80-year-old Japanese woman was admitted to our hospital for
      evaluation of severe anasarca and weight gain (10 kg in a month). She had
      polyneuropathy, monoclonal plasma cell proliferative disorder with positive kappa
      M-protein, a sclerotic bone lesion, elevation of vascular endothelial growth
      factor (VEGF), skin changes, and extravascular volume overload, which fulfilled
      the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy,
      and monoclonal protein, skin changes) syndrome. However, kappa-type M-protein and
      thrombocytopenia with positivity of platelet-associated immunoglobulin G antibody
      were unusual, and fitted the diagnostic criteria for TAFRO syndrome. Renal biopsy
      showed diffuse endocapillary proliferative glomerulonephritis with endothelial
      swelling and the infiltration of monocytes and neutrophils without specific
      immunoglobulin deposits. Her systemic symptoms were refractory to initial
      treatment with high-dose melphalan and glucocorticoids. Alternative therapy with
      an anti-interleukin-6 (IL-6) receptor antibody (tocilizumab) effectively
      controlled the symptoms, while a thrombopoietin receptor agonist (romiplostim)
      was effective for her thrombocytopenia. Results suggest that IL-6-VEGF axis and
      an autoimmune mechanism may be responsible for TAFRO syndrome with clinical
      features of POEMS and refractory thrombocytopenia, which can be successfully
      treated with combination of tocilizumab and romiplostim.

PMID- 29468525
TI  - Valproic Acid Promotes Apoptosis and Cisplatin Sensitivity Through Downregulation
      of H19 Noncoding RNA in Ovarian A2780 Cells.
AB  - Cisplatin resistance is one of the main limitations in the treatment of ovarian
      cancer, which is partly mediated by long noncoding RNAs (lncRNAs). H19 is a
      lncRNA involving in cisplatin resistance in cancers. Valproic acid (VPA) is a
      commonly used drug for clinical treatment of seizure disorders. In addition, this
      drug may display its effects through regulation of noncoding RNAs controlling
      gene expression. The aim of the present study was the investigation of VPA
      treatment effect on H19 expression in ovarian cancer cells and also the relation
      of the H19 levels with apoptosis and cisplatin resistance. Briefly, treatment
      with VPA not only led to significant increase in apoptosis rate, but also
      increased the cisplatin sensitivity of A2780/CP cells. We found that following
      VPA treatment, the expression of H19 and EZH2 decreased, but the expression of
      p21 and PTEN increased significantly. To investigate the involvement of H19 in
      VPA-induced apoptosis and cisplatin sensitivity, H19 was inhibited by a specific
      siRNA. Our results demonstrate that H19 knockdown by siRNA induced apoptosis and
      sensitized the A2780/CP cells to cisplatin-induced cytotoxicity. These data
      indicated that VPA negatively regulates the expression of H19 in ovarian cancer
      cells, which subsequently leads to apoptosis induction, cell proliferation
      inhibition, and overwhelming to cisplatin resistance. The implication of H19
      >EZH2->p21/PTEN pathway by VPA treatment suggests that we could repurpose an old
      drug, valproic acid, as an effective drug for treatment of ovarian cancer in the
      future.

PMID- 29468526
TI  - Attention deficit hyperactivity disorder pharmacotherapy in Slovenian adults: a
      population-based study.
AB  - Background Pharmacotherapy is the first line treatment for adult attention
      deficit hyperactivity disorder (ADHD) and the percentage of treated patients may
      indicate the quality of treatment of adult ADHD. The main aim of this study was
      to investigate the rates of pharmacological treatment for adult ADHD in Slovenia
      from 2003 to 2015. Methods The number of prescriptions per patient was obtained
      for three different age groups (18-24, 25-49, 50 + age group). The national
      consumption rates were obtained from the national database. The only drugs that
      were available and were included in this study were methylphenidate (MPH) and
      atomoxetine (ATX). Results Between 2003 and 2015 the rate of patients aged 18-24
      who were treated with MPH increased from 0.8 per 10,000 people aged 18-24 to 8.9
      per 10,000 people, while the increase in the other two age groups was less
      substantial (25-49, 50 + age group). The rate of patients aged 18-24 treated with
      ATX in 2015 was 7.3 per 10,000 people and 2.2 per 10,000 people in the 25-49 age
      category and 0.28 in the 50 + age group category. Conclusion Prescription rates
      of ADHD medication have increased dramatically in the study period. The high
      proportion of ADHD patients treated with ATX can be explained by low adherence to
      treatment guidelines. This is the first study to compare ADHD pharmacotherapy
      across different adult age groups in this part of Europe, so the results could be
      widely relevant.

PMID- 29468527
TI  - Collaborative practice agreement in solid organ transplantation.
AB  - Background Given the complexity of solid organ transplant recipients, a
      multidisciplinary approach is required. To promote medication safety and enable
      providers to focus on the medical and surgical needs of these patients, our
      department of pharmacy created a collaborative practice agreement between
      physicians and pharmacists. Through this agreement, credentialed pharmacists are
      empowered to provide inpatient services including initiation and adjustment of
      medications through independent review of laboratory results after
      multidisciplinary rounds. Objective To evaluate the effect of our collaborative
      practice agreement on clinical care and institutional finances. Setting An
      inpatient setting at a large academic medical center. Methods Three transplant
      pharmacists entered all clinical interventions made on abdominal transplant
      recipients between September and October 2013 into Quantifi(r), a software
      application that categorizes and assigns a cost savings value based on impact and
      type of intervention. Main outcome measure The main outcome measures in this
      study were number and categorization of interventions, as well as estimated cost
      savings to the institution. Results There were 1060 interventions recorded, an
      average of 20 interventions per pharmacist per day. The most common interventions
      were pharmacokinetic evaluations (36%) and dose adjustments (19%). Over the time
      period, these interventions translated into an estimated savings of $107,634.00,
      or an annual cost savings of $373,131.20 per pharmacist, or a cost-benefit ratio
      of 2.65 to the institution. Conclusions Based on our study, implementation of a
      collaborative practice agreement enables credentialed pharmacists to make
      clinically and financially meaningful interventions in a complex patient
      population.

PMID- 29468528
TI  - The influence of pharmacist-led adherence support on glycaemic control in people
      with type 2 diabetes.
AB  - Background Adherence to treatment is important to achieve target outcomes,
      particularly for those with type 2 diabetes. Pharmacists are well placed to
      enhance adherence, however evidence of the impact on clinical outcomes is not
      well known. Objective To determine the impact of an adherence support service on
      adherence scores and subsequent clinical biomarkers (HbA1c). Setting Community
      pharmacies providing a Medicines Use Review (MUR) Service in a New Zealand
      locality. Methods Records of patients receiving MURs between 2007 and 2012 were
      obtained from a single locality. Data extraction included: individual
      characteristics, the adherence score assigned at every consultation, pathology
      records. Patients receiving oral hypoglycaemic medications (n = 86) were included
      in the final analysis using generalised estimating equations to explore change in
      HbA1c over time, and whether this was related to the adherence score. Main
      Outcome Measures (a) change in adherence scores and (b) association between
      adherence sores and HbA1c. Results A total of 350 records were obtained, of
      those, 115 of 350 people had follow up MUR visit/s and could be analysed for
      changes in adherence. Most people (110/115) showed sustained or improved
      adherence scores with follow up visits. For those receiving oral hypoglycaemic
      medications (n = 86); where poor adherence scores were recorded, their HbA1c
      levels were higher and continued to increase by ~ 0.1% (1 mmol/mol) every 10
      weeks, B = 0.11, p = 0.009. Conversely, those with high adherence scores showed
      an overall decrease in HbA1c levels. Conclusion MURs may positively influence
      medication adherence. This improved adherence shows a measurable decline in HbA1c
      levels.

PMID- 29468529
TI  - Right Ventricular Dysfunction and Its Contribution to Morbidity and Mortality in
      Left Ventricular Heart Failure.
AB  - PURPOSE: In patients with left-sided HF, there has been less emphasis on the
      pathophysiology of the RV in terms of diagnostic evaluation and treatment, versus
      focus on structural abnormalities of the LV. This review seeks to delineate the
      importance of RV dysfunction in terms of its contribution to symptomatic
      limitations and cardiovascular outcomes in patients with left-sided HF. RECENT
      FINDINGS: Recent studies have demonstrated that RV dysfunction is common in both
      HFpEF and HFrEF, but more pronounced in HFrEF. LV dysfunction and atrial
      fibrillation are most commonly associated with RV dysfunction in left-sided HF.
      RV dysfunction may develop due to afterload-dependent and afterload-independent
      pathways. Regardless, RV dysfunction is strongly associated with functional
      limitations and worsened survival in patients with left-sided HF. In patients
      with HFpEF, a recent study showed that RV failure was the most common cause of
      overall mortality. Among LVAD patients and patients post-cardiac transplantation,
      RV dysfunction is also strongly associated with survival. Despite a number of
      previous and ongoing clinical trials that target the RV directly or decrease RV
      afterload in left-sided HF, there are no definitive therapies specifically
      targeting RV dysfunction in left-sided HF patients CONCLUSIONS: RV dysfunction is
      an important determinant of symptomatic limitations and cardiovascular outcomes
      in patients with left-sided HF. Further research is needed to developed
      pharmacotherapy that may target the RV specifically in left-sided HF patients.

PMID- 29468530
TI  - The Future of Biomarker-Guided Therapy for Heart Failure After the Guiding
      Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure
      (GUIDE-IT) Study.
AB  - PURPOSE OF REVIEW: Biomarker-guided management of patients with chronic heart
      failure with reduced ejection fraction (HFrEF) remains controversial. RECENT
      FINDINGS: Biomarkers have established roles for diagnosis and prognostication in
      HF. Pilot data suggested that use of natriuretic peptides might be helpful to
      guide HF care. The recent Guiding Evidence-Based Therapy Using Biomarker
      Intensified Treatment in Heart Failure (GUIDE-IT) randomized-controlled trial did
      not find therapy guided by NT-proBNP to be more effective than usual care in
      improving the primary endpoint of HF hospitalization or cardiovascular mortality
      amongst patients with chronic HFrEF. Patients in GUIDE-IT received similar care
      and had similar NT-proBNP lowering regardless of treatment allocation. Though
      biomarkers retain important standing for diagnosis and prognosis in HF, the GUIDE
      IT trial results suggest carefully managed patients may not benefit from a
      biomarker-guided strategy. Future studies focusing this intervention on patients
      treated in a more real-world setting are needed.

PMID- 29468531
TI  - Editor's reply to "Mobile applications for colorectal surgery journals: Do we
      really need them?"

PMID- 29468532
TI  - Meta-analyses of HIV prevention interventions targeting improved partner
      communication: effects on partner communication and condom use frequency
      outcomes.
AB  - Behavioral HIV prevention interventions designed to improve safer-sex
      communication skills with sexual partners may enhance engagement in protective
      behaviors and reduce HIV/STI risk. The current meta-analyses examined the
      efficacy of individual-based (i.e., not couples-based) HIV prevention
      interventions with a partner communication skills building component to increase
      frequency of: (a) safer-sex communication and (b) condom use with sexual partners
      among HIV at-risk groups (e.g., heterosexual African American females). Studies
      were retrieved from online bibliographic databases, a database of effective
      behavioral HIV prevention interventions, and an existing review of effective
      interventions. Eight manuscripts (k = 10 intervention vs. control comparisons)
      met inclusion criteria. Results indicated that compared to control conditions, at
      post-intervention follow-up, participants who were exposed to individual-based
      HIV prevention interventions with safer-sex communication skills training
      components had safer sex discussions with partners more frequently [drandom =
      0.35 +/- 0.10, p < .001, 95% CI (0.16, 0.55)], and used condoms more frequently
      [drandom = 0.39 +/- 0.07, p < .001, 95% CI (0.25, 0.54)]. Including partner
      communication skills training in individual-based HIV prevention interventions
      may increase the frequency of both partner communication and condom use among the
      at-risk populations represented in the meta-analyses.

PMID- 29468533
TI  - Recalled early life adversity and pain: the role of mood, sleep, optimism, and
      control.
AB  - Early life adversity (ELA) has been associated with pain symptomatology in
      adulthood, but mechanisms and moderators of these associations are unclear. Using
      recall based and concurrently assessed self-report data, we examined associations
      between ELA, mood, sleep, and recent pain intensity and interference, and whether
      optimism and perceived control weakened these associations in a midlife community
      sample of diverse adults reporting some ELA. Controlling for demographic
      variables and BMI, higher levels of ELA were associated with more pain intensity
      and interference; greater sleep disturbance and negative mood accounted for these
      associations. When moderation was examined, only the path from sleep disturbance
      to pain interference was significantly attenuated for those with higher optimism
      and higher perceived control. These findings suggest that higher levels of ELA
      may link with pain in adulthood through poorer mood and sleep, and that
      resilience resources such as optimism and control may buffer some of these
      pathways.

PMID- 29468535
TI  - Methodological Implications and Repeatability of Nasal Nitric Oxide: Relevance
      for Challenge Studies.
AB  - There is an interest in assessing changes in nasal NO (nNO) levels as an effect
      marker of upper airways. In this study, we examined methodologic influences on
      short and long term repeatability of nNO levels assessed by a portable
      electrochemical analyzer. Nine atopic and eighteen healthy subjects were exposed
      for 4 h to ethyl acrylate concentration of 0.05 ppm (sham) and mean
      concentrations of 5 ppm (either constant 5 ppm or variable 0 to 10 ppm). Sampling
      of nNO was performed by using passive aspiration during both breath-holding (634
      ppb) or calm tidal breathing (364 ppb, p < 0.0001). The intra-session (between
      session) repeatability in terms of coefficient of variation was 16.4% (18.5%)
      using the tidal-breathing and 8.6% (13.0%) using the breath-holding method,
      respectively. Atopic subjects demonstrated a significant increase in nNO (breath
      holding mean 16%, tidal-breathing mean 32%) after applying a constant ethyl
      acrylate concentration (5 ppm). Our findings suggest that the less elaborate
      tidal-breathing method might be sufficient to detect significant changes at a
      group level. Given a lower coefficient of variation of breath-holding we assume
      there is an advantage of that approach at an individual level. Further research
      is needed to validate the usefulness of nNO in the evaluation of irritative, non
      allergic responses.

PMID- 29468536
TI  - Correction to letter: Image-guided thermal ablation of benign thyroid nodules.
AB  - The original version of this article unfortunately was incorrect. The correct
      title should read: "Comment to article: "Image-guided thermal ablation of benign
      thyroid nodules" by A. Mainini, et al. J Ultrasound (2017)
      https://doi.org/10.1007/s40477-016-0221-6 ".

PMID- 29468534
TI  - Body Covering and Body Image: A Comparison of Veiled and Unveiled Muslim Women,
      Christian Women, and Atheist Women Regarding Body Checking, Body Dissatisfaction,
      and Eating Disorder Symptoms.
AB  - Although Islam is the fastest growing religion worldwide, only few studies have
      investigated body image in Muslim women, and no study has investigated body
      checking. Therefore, the present study examined whether body image, body
      checking, and disordered eating differ between veiled and unveiled Muslim women,
      Christian women, and atheist women. While the groups did not differ regarding
      body dissatisfaction, unveiled Muslim women reported more checking than veiled
      Muslim and Christian women, and higher bulimia scores than Christian. Thus,
      prevention against eating disorders should integrate all women, irrespective of
      religious affiliation or veiling, with a particular focus on unveiled Muslim
      women.

PMID- 29468538
TI  - Characterization of RB1 Deletions in Interphase and Metaphase by Molecular
      Cytogenetics Exemplified in Chronic Lymphatic Leukemia.
AB  - In chronic lymphatic leukemia (CLL), detection and characterization of prognostic
      relevant chromosomal alterations is optimally done by interphase-fluorescence in
      situ hybridization (iFISH). Interphase nuclei derived from blood smears, bone
      marrow smears or from cultivated and conventionally prepared blood or bone marrow
      cells can be used. In CLL heterozygous or even homozygous deletion of RB1 can be
      found. Interestingly an iFISH diagnostic result with RB1 deletion as sole
      aberration is indicative for a favorable course of the disease. Here we describe
      the best way how to detect RB1 deletion in CLL.

PMID- 29468537
TI  - Hepatitis A Virus Disinfection in Water by Solar Photo-Fenton Systems.
AB  - This study evaluates and compares the effectiveness of solar photo-Fenton systems
      for the inactivation of hepatitis A virus (HAV) in water. The effect of solar
      irradiance, dark- Fenton reaction and three different reactant concentrations
      (2.5/5, 5/10 and 10/20 mg/L of Fe2+/H2O2) on the photo-Fenton process were tested
      in glass bottle reactors (200 mL) during 6 h under natural sunlight. Disinfection
      kinetics were determined both by RT-qPCR and infectivity assays. Mean water
      temperatures ranged from 25 to 27.3  degrees C, with a maximum local noon UV
      irradiances of 22.36 W/m2. Photo-Fenton systems yielded increased viral reduction
      rates in comparison with the isolated effect under the Fenton reaction in
      darkness (negligible viral reduction) or the solar radiation (0.25 Log of RNA
      reduction). With the highest concentration employed (10-20 mg/L Fe2+-H2O2), an
      average RNA reduction rate of ~ 1.8 Log (initial concentration of 105 pfu/mL) and
      a reduction of 80% in the infectivity capacity were reached. Results showed a
      strong synergistic effect between Fe2+/H2O2 and sunlight, demonstrating that
      significant disinfection rates of HAV under photo-Fenton systems may occur with
      relatively higher efficiency at middle environmental temperatures and without the
      need for an energy-intensive light source.

PMID- 29468539
TI  - Detection of RB1 Gene Copy Number Variations Using a Multiplex Ligation-Dependent
      Probe Amplification Method.
AB  - Multiplex ligation-dependent probe amplification (MLPA) is based on simultaneous
      multiplex PCR of specific probes that hybridize to multiple different target DNA
      regions. The method can identify copy number changes, gross gene rearrangements,
      methylation patterns or even point mutations. MLPA has been a reliable approach
      to identify copy number changes in the clinical and research settings and is
      widely used for the screening and investigation of copy number variations and
      genomic aberrations of interest in various diseases. In this chapter the analysis
      of the copy number changes in the RB1 gene locus by MLPA is described.

PMID- 29468540
TI  - A Fluorescent Quantitative Multiplex PCR Method to Detect Copy Number Changes in
      the RB1 Gene.
AB  - Copy number changes comprising deletions or insertions involving single or
      multiple exons of a gene are known to occur in a significant proportion of cases
      in retinoblastoma. The protocol described here involves a two-step quantitative
      multiplex PCR process which is suitable for the detection of such mutations in
      the RB1 as well as in other genes. This is achieved through the use of suitable
      gene-specific primers designed to amplify individual exons, with universal tags
      attached to the 5' end of each primer. These tagged primers are used in the first
      step of PCR of the RB1 gene in patients. The second step is carried out through
      the use of "universal" primers complementary to the tag sequences alone. This
      technique facilitates the detection of fluorescent PCR products from multiple
      exons through the use of a single fluorescent tagged primer.

PMID- 29468541
TI  - Using Methylation-Specific PCR to Study RB1 Promoter Hypermethylation.
AB  - It has increasingly been considered crucial the understanding of DNA methylation
      of Tumor Suppressor Gene (TSG) promoters, such as that of retinoblastoma 1 gene
      (RB1), and its role during carcinogenesis. We present a detailed and optimized
      protocol of the methylation-specific PCR (MSP) technique to study RB1 gene
      promoter hypermethylation.

PMID- 29468542
TI  - Detection of Aberrant DNA Methylation Patterns in the RB1 Gene.
AB  - The retinoblastoma protein (pRb) plays a central role in the regulation of cell
      cycle by interaction with members of the E2F transcription factor family. As a
      tumor suppressor protein, pRb is frequently dysregulated in several major
      cancers. In addition to mutations, inactivation of pRb is also caused by
      epigenetic mechanisms including alterations of DNA methylation. There are three
      CpG islands located within the RB1 gene that encodes pRb that are closely
      associated with the regulation of pRb expression. Aberrant DNA methylation at the
      RB1 gene has been reported in sporadic retinoblastoma as well as other cancers
      including glioblastoma, hepatocellular carcinoma, and breast cancer. Recent
      studies have revealed that the RB1 gene is imprinted. Therefore, quantitative
      analysis is required to detect aberrations in DNA methylation associated with
      imprint deregulation. Pyrosequencing(r) is considered as the method of choice for
      quantitative and reproducible analysis of DNA methylation with single base
      resolution. In this chapter, we provide a detailed protocol for the quantitative
      analysis of RB1 gene methylation using bisulfite Pyrosequencing(r).

PMID- 29468543
TI  - Detection of Retinoblastoma Protein Phosphorylation by Immunoblot Analysis.
AB  - The retinoblastoma tumor suppressor protein (pRb) is a preeminent tumor
      suppressor that acts as a cell cycle repressor, specifically as an inhibitor of
      the G1-S transition of the cell cycle . pRb is a phosphoprotein whose function is
      repressed by extensive phosphorylation in several key residues, and therefore,
      pRb's phosphorylation status has become a surrogate for pRb activity. In
      particular, hyperphosphorylation of pRb has been associated with pathological
      states such as cancer, and therefore, assessing pRb's phosphorylation status is
      increasingly gaining diagnostic and prognostic value, may be used to inform
      therapeutic decisions, and is also an important tool for the cancer biologists
      seeking an understanding of the molecular etiology of cancer. In this chapter, we
      discuss an immunoblot protocol to detect pRb phosphorylation in two residues,
      serine 612 and threonine 821, in protein extracts from cancer cells.

PMID- 29468545
TI  - Immunohistochemical Detection of Retinoblastoma Protein Phosphorylation in Human
      Tumor Samples.
AB  - The retinoblastoma protein (pRb) is an important tumor suppressor and cell cycle
      repressor. pRb is a phosphoprotein whose function is regulated primarily at the
      level of phosphorylation, and therefore, detecting pRb's phosphorylation status
      in human tissue samples can be clinically informative. Unfortunately, detection
      of phosphorylated pRb residues can be technically challenging, as these residues
      can often be weak antigens. In this chapter, we describe an enhanced sensitivity
      immunohistochemistry protocol for the staining of phosphorylated serine 249 in
      pRb, in human lung tumor samples.

PMID- 29468544
TI  - Immunohistochemical Detection of the Retinoblastoma Protein.
AB  - The retinoblastoma protein (pRB) plays a key role in proliferative control and
      genome stability. For these reasons its functions are considered to be tumor
      suppressive. Its functional status offers critical insight into proliferative
      control signaling in tissues and in developing malignancies. In this chapter, we
      outline basic procedures to detect the retinoblastoma protein in formalin fixed,
      paraffin embedded tissue sections. In addition, we provide protocols to detect
      phosphorylation levels of pRB in tissues and offer controls to ensure fidelity of
      measurement. Importantly, these staining methods utilize broadly available
      reagents and equipment making them accessible to most biomedical research
      laboratories.

PMID- 29468546
TI  - Detection of CCND1 Locus Amplification by Fluorescence In Situ Hybridization.
AB  - It is well known that chromosomal aberrations of tumors are associated with the
      initiation and progression of malignancy. Fluorescence in situ hybridization
      (FISH) is a powerful, rapid method to detect chromosome copy number and
      structural alterations in tissue sections, chromosome, or interphase cellular
      preparations via hybridization of complementary probe sequences. The technique is
      based on the complementary nature of DNA double strands, which allows
      fluorescently labeled DNA probes to be used as probes to label the complementary
      sequences of target cells, chromosomes, and tissues. FISH technique has many
      applications, including basic gene mapping, used in pathological diagnosis to
      detect chromosome and gene copy number aberrations, translocations,
      microdeletions, and duplications. For the recognition of gene amplifications and
      deletions, locus-specific probes that are collections of one or a few cloned DNA
      sequences are routinely used. Multiplex-FISH (M-FISH) technique visualizes all
      chromosomes with different colors using spectrally distinct fluorophores for each
      chromosome in one experiment to detect numerical and structural alterations of
      chromosomes obtained from tumor cells. Recently many of the gene-specific probes
      are commercially available.

PMID- 29468547
TI  - Detection of CCND1 Gene Copy Number Variations Using Multiplex Ligation-Dependent
      Probe Amplification and Fluorescence In Situ Hybridization Methods.
AB  - The CCND1 locus is located in 11q13 and encodes the G1-S regulatory protein,
      cyclin D1. Cyclin D1 is frequently amplified in various types of cancers, and is
      an attractive potential therapeutic target. Multiplex ligation-dependent probe
      amplification (MLPA) is a new, high-resolution method for the detection of
      amplification of numerous genes including CCND1 in small amounts of DNA fragments
      derived from formalin-fixed, paraffin-embedded material in a single reaction.
      This approach is, however, based on PCR and averages many different cells, so
      validation by morphological methods such as fluorescence in situ hybridization
      (FISH) is theoretically mandatory. Here we describe detection of CCND1 gene copy
      number variations by commercially available MLPA kits and FISH using a bacterial
      artificial chromosome (BAC) probe.

PMID- 29468548
TI  - Detection of p16 Promoter Hypermethylation by Methylation-Specific PCR.
AB  - DNA methylation plays a decisive role in the regulation and control of gene
      expression. DNA methylation is a covalent modification, in which a methyl group
      is attached to the 5th carbon of the cytosine ring of a CpG dinucleotide that is
      located upstream from the promoter region of a gene. Promoter hypermethylation
      (gain of DNA methylation) of the p16 gene may cause silencing of gene expression
      and plays an important role in cancer. Therefore, detection of the methylation
      status of p16 gene is an important tool in epigenetic studies of various human
      cancers. The methylation-specific PCR (MSP) is the most commonly used technique
      for studying DNA methylation. This technique is based on bisulfite modification
      of DNA, which converts unmethylated cytosine (C) into uracil (U) and leaving
      methylated cytosine (Cm) unchanged. Here we describe the bisulfite modification
      of DNA samples and detection of promoter methylation of p16 gene from bisulfite
      treated DNA using MSP. In MSP, modified DNA samples are subjected to PCR
      amplification using methylated and unmethylated specific primers for the p16 gene
      separately. The PCR amplified products are then analyzed in a 2.5-3% agarose gel
      containing ethidium bromide. The PCR amplified band generated by specific sets of
      primers is used to determine the methylation status of the p16 gene.

PMID- 29468549
TI  - Immunohistochemical Detection of p16 in Clinical Samples.
AB  - P16 immunohistochemical expression, a surrogate marker of the retinoblastoma
      pathway, has become a major adjunct in the routine practice mostly of cervical
      and head/neck pathology, but with other indications too. In this chapter, a
      detailed immunohistochemical technique for the detection of p16 is described,
      followed by indications and interpretation of its expression in uterine, ovarian,
      vulvar, penile, head-and-neck, melanocytic, and other pathologies.

PMID- 29468550
TI  - Detection of E2F-DNA Complexes Using Chromatin Immunoprecipitation Assays.
AB  - Chromatin immunoprecipitation (ChIP), originally developed by John T. Lis and
      David Gilmour in 1984, has been useful to detect DNA sequences where protein(s)
      of interest bind. ChIP is comprised of several steps: (1) cross-linking of
      proteins to target DNA sequences, (2) breaking genomic DNA into 300-1000 bp
      pieces by sonication or nuclease digestion, (3) immunoprecipitation of protein
      bound to target DNA with an antibody, (4) reverse cross-linking between target
      DNA and the bound protein to liberate the DNA fragments, and (5) amplification of
      target DNA fragment by PCR. Since then, the technology has evolved significantly
      to allow not only amplifying target sequences by PCR, but also sequencing all DNA
      fragment bound to a target protein, using a variant of the approach called the
      ChIP-seq technique (1). Another variation, the ChIP-on-ChIP, allows the detection
      of protein complexes bound to specific DNA sequences (2).

PMID- 29468551
TI  - Detection of E2F-Induced Transcriptional Activity Using a Dual Luciferase
      Reporter Assay.
AB  - The E2F transcription factors are key targets for the retinoblastoma (RB) tumor
      suppressor function. The active or inactive status of RB determines the degree by
      which E2F-dependent gene expression will occur in a given condition. Changes in
      transcriptional activity in response to extracellular or intracellular stimuli
      are frequently measured using genetic reporter assays. In particular, dual
      luciferase reporter assays are most recommended for this purpose because of their
      improved experimental accuracy. Here we illustrate the usefulness of the dual
      luciferase reporter assay to detect E2F-mediated transcriptional activity upon
      overexpression of E2F1 in cultured cells as readout for RB status and function.

PMID- 29468552
TI  - Detection of HPV E6/E7 mRNA in Clinical Samples Using RNA In Situ Hybridization.
AB  - Detection of human papilloma virus (HPV) in tissue specimens has been a clinical
      challenge since last 2 decades; however, screening for presence of E6/E7
      transcripts is regarded as the gold standard, and it verifies the active HPV
      infection. Here, we describe "RNAscope(r) assay" a novel RNA in situ
      hybridization (ISH) technology; which detects E6/E7 mRNA of seven high risk HPV
      subtypes (HPV 16, 18, 31, 33, 35, 52, and 58) in formalin fixed paraffin embedded
      (FFPE) tissue samples.

PMID- 29468553
TI  - CRISPR/Cas9-Mediated Knockout of Rb1 in Xenopus tropicalis.
AB  - At this time, no molecular targeted therapies exist for treatment of
      retinoblastoma. This can be, in part, attributed to the lack of animal models
      that allow for both rapid identification of novel therapeutic targets and
      hypothesis driven drug testing. Within this scope, we have recently reported the
      first genuine genetic nonmammalian retinoblastoma cancer model within the aquatic
      model organism Xenopus tropicalis (Naert et al., Sci Rep 6: 35263, 2016). Here we
      describe the methods to generate rb1 mosaic mutant Xenopus tropicalis by
      employing the CRISPR/Cas9 technology. In depth, we discuss short guide RNA
      (sgRNA) design parameters, generation, quality control, quantification, and
      delivery followed by several methods for assessing genome editing efficiencies.
      As such the reader should be capable, by minor changes to the methods described
      here, to (co-) target rb1 or any one or multiple gene(s) within the Xenopus
      tropicalis genome by multiplex CRISPR/Cas9 methodology.

PMID- 29468554
TI  - SDF 1-alpha Attenuates Myocardial Injury Without Altering the Direct Contribution
      of Circulating Cells.
AB  - Stromal cell-derived factor 1-alpha (SDF) is a potent bone marrow chemokine
      capable of recruiting circulating progenitor populations to injured tissue. SDF
      has known angiogenic capabilities, but bone marrow-derived cellular contributions
      to tissue regeneration remain controversial. Bone marrow from DsRed-transgenic
      donors was transplanted into recipients to lineage-trace circulating cells after
      myocardial infarction (MI). SDF was delivered post-MI, and hearts were evaluated
      for recruitment and plasticity of bone marrow-derived populations. SDF treatment
      improved ventricular function, border zone vessel density, and CD31+ cell
      frequency post-MI. Bone marrow-derived endothelial cells were observed; these
      cells arose through both cell fusion and transdifferentiation. Circulating cells
      also adopted cardiomyocyte fates, but such events were exceedingly rare and
      almost exclusively resulted from cell fusion. SDF did not significantly alter the
      proportion of circulating cells that adopted non-hematopoietic fates. Mechanistic
      insight into the governance of circulating cells is essential to realizing the
      full potential of cytokine therapies.

PMID- 29468555
TI  - A model for predicting sulcus-to-sulcus diameter in posterior chamber phakic
      intraocular lens candidates: correlation between ocular biometric parameters.
AB  - PURPOSE: The aim of this study was to determine the correlation between ocular
      biometric parameters and sulcus-to-sulcus (STS) diameter. METHODS: This was a
      cross-sectional study of preoperative ocular biometry data of patients who were
      candidates for phakic intraocular lens (IOL) surgery. Subjects underwent ocular
      biometry analysis, including refraction error evaluation using an autorefractor
      and Orbscan topography for white-to-white (WTW) corneal diameter and measurement.
      Pentacam was used to perform WTW corneal diameter and measurements of minimum and
      maximum keratometry (K). Measurements of STS and angle-to-angle (ATA) were
      obtained using a 50-MHz B-mode ultrasound device. Anterior optical coherence
      tomography was performed for anterior chamber depth measurement. Pearson's
      correlation test and stepwise linear regression analysis were used to find a
      model to predict STS. RESULTS: Fifty-eight eyes of 58 patients were enrolled.
      Mean age +/- standard deviation of sample was 28.95 +/- 6.04 years. The Pearson's
      correlation coefficient between STS with WTW, ATA, mean K was 0.383, 0.492, and -
      0.353, respectively, which was statistically significant (all P < 0.001). Using
      stepwise linear regression analysis, there is a statistically significant
      association between STS with WTW (P = 0.011) and mean K (P = 0.025). The
      standardized coefficient was 0.323 and - 0.284 for WTW and mean K, respectively.
      The stepwise linear regression analysis equation was: (STS = 9.549 + 0.518 WTW -
      0.083 mean K). CONCLUSION: Based on our result, given the correlation of STS with
      WTW and mean K and potential of direct and essay measurement of WTW and mean K,
      it seems that current IOL sizing protocols could be estimating with WTW and mean
      K.

PMID- 29468556
TI  - What Is the Minimum Number of Examined Lymph Nodes After Neoadjuvant Therapy in
      Rectal Cancer?
AB  - BACKGROUND: To date, no guidelines have standardized the number of examined lymph
      nodes (eLNs) after neoadjuvant treatment. This study investigated the minimum
      number of eLNs required for patients with rectal cancer (RC) who received
      neoadjuvant treatment. MATERIAL AND METHODS: This study was based on data from
      the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database.
      We included 2173 patients with RC who received neoadjuvant therapy. Restricted
      cubic spline was used to analyze the association between eLNs and lymph node
      metastasis (LNM). RESULTS: The number of eLNs was an independent predictive
      factor for the presence of LNM (odds ratio 1.033; 95% confidence interval 1.020
      1.046; P < 0.001). When the number of eLN <= 16, 10 and 11 eLNs had the highest
      rates of positive LNM. Analysis of the restricted cubic spline method found that
      when number of eLNs was < 10, the LNM rate increased rapidly, but this increase
      was not so obviously when there were > 10 eLNs. CONCLUSIONS: Among RC patients
      who receive neoadjuvant therapy, the minimum number of eLNs may be 10 to ensure
      pathological quality.

PMID- 29468557
TI  - Shear wave elastography in the diagnostics of parathyroid adenomas-new
      application of the method.
AB  - PURPOSE: Shear wave elastography (SWE) was described as valuable tool in the
      diagnostics of distinct types of thyroid lesions, thyroiditis and several other
      non-thyroidal conditions, such as liver inflammation and fibrosis or diagnostics
      of breast lesions. The aim of the current study was to assess the appearance of
      parathyroid adenomas in SWE and to check prospectively if SWE can be valuable
      additional tool in the diagnostics of pathologically enlarged parathyroids.
      METHODS: Patients with parathyroid adenomas confirmed by histopathology were
      included. Subjects with benign thyroid lesions were enrolled to the control
      group. Elasticity of parathyroid adenomas and benign thyroid nodules was measured
      and compared. RESULTS: Sixty five patients with parathyroid adenomas and 35
      patients with 51 benign thyroid nodules were included. Parathyroid adenomas where
      significantly more elastic than benign thyroid nodules-mean elasticity of the
      lesion was 5.2 +/- 7.2 vs. 24.3 +/- 33.8 kPa, respectively. Relative mean
      elasticity (in comparison with surrounding thyroid tissue) was 0.30 +/- 0.36 and
      2.8 +/- 3.9, respectively. CONCLUSIONS: SWE can be useful tool in the diagnostics
      of parathyroid adenomas. Enlarged parathyroids are significantly more elastic
      than benign thyroid lesions. Low elasticity of the lesion constitutes feature
      with high negative prognostic value, allowing for reliable exclusion of suspicion
      of parathyroid adenomas.

PMID- 29468558
TI  - Correction to: Pharmacologically induced impairment of neurovascular coupling
      responses alters gait coordination in mice.
AB  - The original version of this article unfortunately contained an error.

PMID- 29468560
TI  - Author Correction: Exogenous Cannabinoid Efficacy: Merely a Pharmacokinetic
      Interaction?
AB  - In the original publication, Page 3, Sect. 4.3, the first sentence was
      incorrectly published.

PMID- 29468559
TI  - 15 Years of Experience with Biphasic Insulin Aspart 30 in Type 2 Diabetes.
AB  - Since clinical experience with biphasic insulin aspart 30 (BIAsp 30) in type 2
      diabetes mellitus (T2DM) was reviewed in 2012 after 10 years of use worldwide,
      additional studies have been published that highlight new aspects, including use
      in real-world populations. Evidence from 35 new studies confirms and builds upon
      previous work indicating that BIAsp 30 continues to have pharmacodynamic and
      clinical advantages over biphasic human insulin (BHI 30), including in real-world
      practice with unselected populations of patients. BIAsp 30 has also been shown to
      be safe and efficacious as an add-on to dipeptidyl peptidase-4 (DPP-4)
      inhibitors. Intensification with BIAsp 30 is a safe and effective way to improve
      glycemic control, and titration performed by patients can achieve results that
      are at least comparable to those when being guided by healthcare providers.
      Stepwise intensification using BIAsp 30 is comparable to intensification using a
      basal-bolus regimen, and twice-daily BIAsp 30 provides similar glycemic control
      to a basal-plus regimen. Data from large observational studies, in particular,
      have identified patient-related characteristics that are associated with improved
      clinical responses, suggesting that earlier initiation and intensification of
      therapy is warranted. Finally, new health-economic analyses continue to confirm
      that BIAsp 30 is cost effective versus other therapies such as BHI 30, neutral
      protamine Hagedorn (NPH), or insulin glargine in both insulin-naive and insulin
      experienced patients. After 15 years of clinical use worldwide, analysis of more
      recent 5-year data indicates that BIAsp 30 remains a safe, effective, and simple
      to-use insulin for initiation and intensification by diabetes specialists and
      primary care physicians in a variety of patients with T2DM.

PMID- 29468561
TI  - Chronic pain in medullary sponge kidney: a rare and never described clinical
      presentation.
AB  - Medullary sponge kidney (MSK) is a cause of nephrocalcinosis, associated with
      hematuria, renal colic, pyelonephritis. There are rare and atypical MSK cases
      characterized by chronic severe pain (CP), whose features are unknown, in
      particular the relationship with the stone disease activity. This study analyzes
      a cohort of MSK-CP patients belonging to three North-America self-support
      Facebook groups. Patients had to self-administer an on-line questionnaire (on
      intensity, progression and MSK-associated conditions, stone-related disease, pain
      features, drug use), the Brief Pain Inventory, the Fatigue Severity Score, and
      Wisconsin Quality of Life (WQL) in stone formers questionnaires. Ninety-two
      patients with a diagnosis of MSK joined our survey. Stone rate was very high (3.1
      stones per patient-year, < 15% of patients had <= 1 stone per year). Most
      patients had repeated hospitalizations for stones symptoms (p < 0.001) or pain (p
      < 0.005). 71% of participants referred a daily pain that interfered strongly with
      everyday life and quality of life (WQL mean value 29.4). 69% used pain
      medications daily (70% opioids). In most cases, pain was associated with stone
      passage, while 15% referred a sine materia pain. We showed how MSK-CP symptoms
      affect very negatively on the quality of life of these patients. They also have a
      definite risk of progressing to end-stage kidney disease. Generally, CP seems to
      be associated with an exceptionally high lithogenic activity, suggesting that a
      better and earlier metabolic treatment for stone prevention should be the first
      approach in these patients before mini-invasive treatments to prevent pain.

PMID- 29468562
TI  - PKCdelta Knockout Mice Are Protected from Dextromethorphan-Induced Serotonergic
      Behaviors in Mice: Involvements of Downregulation of 5-HT1A Receptor and
      Upregulation of Nrf2-Dependent GSH Synthesis.
AB  - We investigated whether a specific serotonin (5-HT) receptor-mediated mechanism
      was involved in dextromethorphan (DM)-induced serotonergic behaviors. We firstly
      observed that the activation of 5-HT1A receptor, but not 5-HT2A receptor,
      contributed to DM-induced serotonergic behaviors in mice. We aimed to determine
      whether the upregulation of 5-HT1A receptor induced by DM facilitates the
      specific induction of certain PKC isoform, because previous reports suggested
      that 5-HT1A receptor activates protein kinase C (PKC). A high dose of DM (80
      mg/kg, i.p.) induced a selective induction of PKCdelta out of PKCalpha, PKCbetaI,
      PKCbetaII, PKCxi, and PKCdelta in the hypothalamus of wild-type (WT) mice. More
      importantly, 5-HT1A receptor co-immunoprecipitated PKCdelta in the presence of
      DM. Consistently, rottlerin, a pharmacological inhibitor of PKCdelta, or PKCdelta
      knockout significantly protected against increases in 5-HT1A receptor gene
      expression, 5-HT turnover rate, and serotonergic behaviors induced by DM.
      Treatment with DM resulted in an initial increase in nuclear factor erythroid-2
      related factor 2 (Nrf2) nuclear translocation and DNA-binding activity, gamma
      glutamylcysteine (GCL) mRNA expression, and glutathione (GSH) level. This
      compensative induction was further potentiated by rottlerin or PKCdelta knockout.
      However, GCL mRNA and GSH/GSSG levels were decreased 6 and 12 h post-DM. These
      decreases were attenuated by PKCdelta inhibition. Our results suggest that
      interaction between 5-HT1A receptor and PKCdelta is critical for inducing DM
      induced serotonergic behaviors and that inhibition of PKCdelta attenuates the
      serotonergic behaviors via downregulation of 5-HT1A receptor and upregulation of
      Nrf2-dependent GSH synthesis.

PMID- 29468563
TI  - Neurobiological Correlates of Alpha-Tocopherol Antiepileptogenic Effects and
      MicroRNA Expression Modulation in a Rat Model of Kainate-Induced Seizures.
AB  - Seizure-triggered maladaptive neural plasticity and neuroinflammation occur
      during the latent period as a key underlying event in epilepsy chronicization.
      Previously, we showed that alpha-tocopherol (alpha-T) reduces hippocampal
      neuroglial activation and neurodegeneration in the rat model of kainic acid (KA)
      induced status epilepticus (SE). These findings allowed us to postulate an
      antiepileptogenic potential for alpha-T in hippocampal excitotoxicity, in line
      with clinical evidence showing that alpha-T improves seizure control in drug
      resistant patients. To explore neurobiological correlates of the alpha-T
      antiepileptogenic role, rats were injected with such vitamin during the latent
      period starting right after KA-induced SE, and the effects on circuitry
      excitability, neuroinflammation, neuronal death, and microRNA (miRNA) expression
      were investigated in the hippocampus. Results show that in alpha-T-treated
      epileptic rats, (1) the number of population spikes elicited by pyramidal
      neurons, as well as the latency to the onset of epileptiform-like network
      activity recover to control levels; (2) neuronal death is almost prevented; (3)
      down-regulation of claudin, a blood-brain barrier protein, is fully reversed; (4)
      neuroinflammation processes are quenched (as indicated by the decrease of TNF
      alpha, IL-1beta, GFAP, IBA-1, and increase of IL-6); (5) miR-146a, miR-124, and
      miR-126 expression is coherently modulated in hippocampus and serum by alpha-T.
      These findings support the potential of a timely intervention with alpha-T in
      clinical management of SE to reduce epileptogenesis, thus preventing chronic
      epilepsy development. In addition, we suggest that the analysis of miRNA levels
      in serum could provide clinicians with a tool to evaluate disease evolution and
      the efficacy of alpha-T therapy in SE.

PMID- 29468565
TI  - Exclusive meningeal relapse of a malignant thymoma after a complete response with
      neoadjuvant chemotherapy.

PMID- 29468564
TI  - Early Presymptomatic Changes in the Proteome of Mitochondria-Associated Membrane
      in the APP/PS1 Mouse Model of Alzheimer's Disease.
AB  - Intracellular beta-amyloid (Abeta) accumulation is an early event in Alzheimer's
      disease (AD) progression. Recently, it has been uncovered that presenilins (PSs),
      the key components of the amyloid precursor protein (APP) processing and the beta
      amyloid producing gamma-secretase complex, are highly enriched in a special sub
      compartment of the endoplasmic reticulum (ER) functionally connected to
      mitochondria, called mitochondria-associated ER membrane (MAM). A current
      hypothesis of pathogenesis of Alzheimer's diseases (AD) suggests that MAM is
      involved in the initial phase of AD. Since MAM supplies mitochondria with
      essential proteins, the increasing level of PSs and beta-amyloid could lead to
      metabolic dysfunction because of the impairment of ER-mitochondrion crosstalk. To
      reveal the early molecular changes of this subcellular compartment in AD
      development MAM fraction was isolated from the cerebral cortex of 3 months old
      APP/PS1 mouse model of AD and age-matched C57BL/6 control mice, then mass
      spectrometry-based quantitative proteome analysis was performed. The enrichment
      and purity of MAM preparations were validated with EM, LC-MS/MS and protein
      enrichment analysis. Label-free LC-MS/MS was used to reveal the differences
      between the proteome of the transgenic and control mice. We obtained 77 increased
      and 49 decreased protein level changes in the range of - 6.365 to + 2.988, which
      have mitochondrial, ER or ribosomal localization according to Gene Ontology
      database. The highest degree of difference between the two groups was shown by
      the ATP-binding cassette G1 (Abcg1) which plays a crucial role in cholesterol
      metabolism and suppresses Abeta accumulation. Most of the other protein changes
      were associated with increased protein synthesis, endoplasmic-reticulum
      associated protein degradation (ERAD), oxidative stress response, decreased
      mitochondrial protein transport and ATP production. The interaction network
      analysis revealed a strong relationship between the detected MAM protein changes
      and AD. Moreover, it explored several MAM proteins with hub position suggesting
      their importance in Abeta induced early MAM dysregulation. Our identified MAM
      protein changes precede the onset of dementia-like symptoms in the APP/PS1 model,
      suggesting their importance in the development of AD.

PMID- 29468566
TI  - Pediatric Psychologists' Collaboration in a National Pediatric Obesity
      Initiative: A Case Study in Interprofessional Collaboration.
AB  - Health Care reform calls for collaborative team-based care; psychologists must
      therefore strengthen their competencies for work in interprofessional clinical
      care settings. Toward that end, a group of psychologists participated with
      physicians, dieticians, physical activity specialists, nurses, and others in a
      national interprofessional workgroup focused on pediatric obesity. The
      interprofessional group was designed to identify areas in need of national
      advocacy, key assessment and treatment concerns, and gaps in internal policies
      and procedures in children's hospitals. This article provides a case report of
      psychologists' roles and experience in this workgroup, and focuses on factors
      that underlie successful collaboration among diverse health professionals, as
      well as potential barriers to success. The participating psychologists developed
      a working model for collaboration with other disciplines. Additionally, they
      formed a Psychology Subcommittee to identify and address discipline-specific
      issues regarding collaborative practice in pediatric psychology. Lessons learned
      in this interprofessional collaborative undertaking have relevance for future
      collaborative endeavors.

PMID- 29468567
TI  - The Role of Optimism, Social Constraints, Coping, and Cognitive Processing in
      Psychosocial Adjustment Among Breast Cancer Survivors.
AB  - The social-cognitive processing model suggests that a socially constrained
      environment may impede adjustment to a chronic illness. The present study
      primarily investigated the mediating psychological pathways through which social
      constraints on cancer-related disclosure, low optimism, disengagement-oriented
      coping, and brooding could be associated with low levels of psychosocial
      adjustment. One hundred twenty-five female breast cancer survivors participated
      in a cross-sectional study. Path analysis was used to examine the proposed model.
      Low optimism, increased social constraints, and higher levels of brooding
      appeared to be risk factors for poor psychosocial adjustment to breast cancer.
      Disengagement-oriented coping and brooding partially mediated the relationship
      between social constraints and adjustment. Brooding totally mediated the
      relationship between disengagement-oriented coping and adjustment. The current
      findings provide support for the value of the social-cognitive processing model
      among breast cancer survivors. The mapping of psychological pathways of
      adjustment to breast cancer may have useful clinical implications for better
      adjustment outcomes.

PMID- 29468568
TI  - Cognitive Behavior Therapy for Fear of Cancer Recurrence: A Case Study.
AB  - This case study describes the course and content of cognitive behavior therapy
      (CBT) for clinical fear of cancer recurrence (FCR) in a breast cancer survivor.
      The CBT for clinical FCR consisted of seven face-to-face therapy sessions and one
      telephone session. The primary treatment goal was to reduce FCR severity by
      modifying cognitive processes and dysfunctional behavior. Assessments of FCR and
      quality of life were completed by the breast cancer survivor pre-therapy, post
      therapy, and at 6 and 12 months of post-therapy. In each treatment session,
      perceived control over FCR was assessed. A clinical nurse specialist participated
      in evaluation interviews. The patient's perceived control over FCR increased
      during the therapy, and FCR severity declined to a non-clinical level. This
      improvement was still evident at the 6- and 12-month follow-up assessments and
      was supported by results for secondary and exploratory outcomes measures. FCR
      offers a great challenge for health care professionals due to the lack of
      effective treatment options. This case study shows how clinical FCR can be
      addressed with CBT and can contribute to the improvement of care for cancer
      survivors.

PMID- 29468569
TI  - Illness Identity in Adults with a Chronic Illness.
AB  - The present study examines the concept of illness identity, the degree to which a
      chronic illness is integrated into one's identity, in adults with a chronic
      illness by validating a new self-report questionnaire, the Illness Identity
      Questionnaire (IIQ). Self-report questionnaires on illness identity,
      psychological, and physical functioning were assessed in two samples: adults with
      congenital heart disease (22-78 year old; n = 276) and with multisystem
      connective tissue disorders (systemic lupus erythematosus or systemic sclerosis;
      17-81 year old; n = 241). The IIQ could differentiate four illness identity
      states (i.e., engulfment, rejection, acceptance, and enrichment) in both samples,
      based on exploratory and confirmatory factor analysis. All four subscales proved
      to be reliable. Rejection and engulfment were related to maladaptive
      psychological and physical functioning, whereas acceptance and enrichment were
      related to adaptive psychological and physical functioning. The present findings
      underscore the importance of the concept of illness identity. The IIQ, a self
      report questionnaire, is introduced to measure four different illness identity
      states in adults with a chronic illness.

PMID- 29468570
TI  - Quality Improvement in Health Care: The Role of Psychologists and Psychology.
AB  - Quality Improvement (QI) is a health care interprofessional team activity wherein
      psychology as a field and individual psychologists in health care settings can
      and should adopt a more robust presence. The current article makes the argument
      for why psychology's participation in QI is good for health care, is good for our
      profession, and is the right thing to do for the patients and families we serve.
      It reviews the varied ways individual psychologists and our profession can
      integrate quality processes and improve health care through: (1) our approach to
      our daily work; (2) our roles on health care teams and involvement in
      organizational initiatives; (3) opportunities for teaching and scholarship; and
      (4) system redesign and advocacy within our health care organizations and health
      care environment.

PMID- 29468571
TI  - Leadership Perspectives on Integrating Psychologists into Specialty Care Clinics:
      An Evolving Paradigm.
AB  - Integration of health psychologists into specialty care is a shift in the
      tertiary care construct that addresses all aspects of a patient's presentation,
      including psychiatric/social history, psychological well-being, and behavioral
      contributions to the disease process, assuring both optimal health outcomes and
      cost-effectiveness in a financially challenging healthcare environment. In this
      paper, we discuss leadership perspectives (physician and psychologists) on the
      factors involved in integrating a health psychologist into a busy tertiary care
      environment. Ultimately, we hope that this information provides a primer on how
      to frame a proposal for an integrated health psychologist emphasizing the
      elements important to senior medical leadership and administration. First, we
      briefly discuss the current payer framework, providing support for integration
      emphasizing costs and other metrics. Second, we introduce organizational
      structure models and strategies for integration. Lastly, we will discuss the
      unique skillset psychologists possess, and additional skills necessary, to be
      effective in the changing landscape of healthcare. We think this information is
      important both for leaders attempting to integrate a health psychologist into
      specialty care and for the early career health psychologist embarking on his/her
      first senior staff position.

PMID- 29468572
TI  - Response to 'No Evidence Against Sketch Reinstatement of Context, Verbal Labels
      or Registered Intermediaries'.

PMID- 29468573
TI  - Relationship Between Odor Identification and Visual Distractors in Children with
      Autism Spectrum Disorders.
AB  - Understanding the nature of olfactory abnormalities is crucial for optimal
      interventions in children with autism spectrum disorders (ASD). However, previous
      studies that have investigated odor identification in children with ASD have
      produced inconsistent results. The ability to correctly identify an odor relies
      heavily on visual inputs in the general population. We tested odor identification
      in eight children with ASD and eight age-matched children with typical
      development (TD). After confirming that all children were able to identify each
      odor without visual input, we measured odor identification under the visual
      distractor condition. Odor identification was hindered by visual distractors for
      all children with ASD but was not affected in all children with TD. Our results
      improve understanding of odor identification in ASD.

PMID- 29468574
TI  - Superior Disembedding in Children with ASD: New Tests Using Abstract, Meaningful,
      and 3D Contexts.
AB  - Since its initial development, the embedded figures test (EFT) has been used
      extensively to measure local-global perceptual style. However, little is known
      about the perceptual factors that influence target detection. The current study
      aimed to investigate disembedding in children with and without ASD, aged 8-15
      years, using the newly developed, stimulus-controlled L-EFT, M-EFT and D-EFT.
      Firstly, results revealed superior disembedding for children with ASD,
      irrespective of the type of target or embedding context, although the ASD group
      took more time in both the M-EFT and D-EFT. Secondly, the number of target lines
      continuing into the context proved more of a hindrance for the controls. Taken
      together, these findings provide strong evidence to support the notion of
      superior disembedding in ASD.

PMID- 29468575
TI  - Autism Spectrum Traits Linked with Reduced Performance on Self-Report Behavioural
      Measures of Cognitive Flexibility.
AB  - Deficits in cognitive flexibility are thought to underpin the core symptom of
      repetitive and restricted patterns of behaviour in autism spectrum disorder
      (ASD). Studies investigating this relationship, however, report inconsistent
      results. This is partly due to the variable nature of measures used to assess the
      construct of flexibility. The main purpose of this study was to investigate
      whether ASD traits differentially predict cognitive flexibility performance on
      lab-based neurocognitive measures relative to behavioural self-reports in a non
      clinical sample of young adults. Our results indicate that ASD traits exclusively
      predict performance on behavioural self-reports of cognitive flexibility. These
      findings highlight the possibility that behavioural self-reports are a better
      index than lab-based neurocognitive measures to capture cognitive flexibility
      impairments in individuals with ASD.

PMID- 29468578
TI  - Does MCDA Trump CEA?

PMID- 29468576
TI  - Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European
      Multi-site Sample of Individuals with Autism Spectrum Disorder.
AB  - Research on sex-related differences in Autism Spectrum Disorder (ASD) has been
      impeded by small samples. We pooled 28 datasets from 18 sites across nine
      European countries to examine sex differences in the ASD phenotype on the ADI-R
      (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early
      childhood restricted and repetitive behaviours were lower in females than males,
      alongside comparable levels of social interaction and communication difficulties
      in females and males. Current ADI-R and ADOS scores showed no sex differences for
      ASD severity. There were lower socio-communicative symptoms in older compared to
      younger individuals. This large European ASD sample adds to the literature on sex
      and age variations of ASD symptomatology.

PMID- 29468577
TI  - Allergy-preventive effects of linarinic acid and its tetrahydropyrrolo[2,1
      b]quinazoline derivatives isolated from Linaria vulgaris.
AB  - Linarinic acid, (-)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid
      (4a), was isolated from the ethanol extract of Linaria vulgaris Mill. In our
      previous study, a series of tetrahydropyrrolo[2,1-b]quinazoline derivatives 4b,
      4c, 5a, 5b, 6a and 6b that were structurally related to 4a and evaluated as
      neuroprotective agents were synthesized. The aim of the present study was to
      investigate the novel features of these compounds. We examined their allergy
      preventive effects using an in vivo assay system we developed previously, that
      monitors a decrease in blood flow in the tail vein of mice subjected to
      sensitization with hen egg-white lysozyme. We observed that 4a and its three
      derivatives, amide (6a), ester (5a), bromine (4b), and alcohol substituent (6b),
      showed significant allergy-preventive activities. The study confirmed the allergy
      preventive activity of tetrahydropyrrolo[2,1-b]quinazoline derivatives by
      comprehensively monitoring the specific blood flow decrease occurring in the
      induction phase of allergy. This finding may aid in the development of new agents
      for the treatment of allergic diseases such as atopic dermatitis, allergic
      asthma, and hay fever.

PMID- 29468579
TI  - Mouse Injury Model of Polytrauma and Shock.
AB  - Severe injury and shock remain major sources of morbidity and mortality
      worldwide. Immunologic dysregulation following trauma contributes to these poor
      outcomes. Few, if any, therapeutic interventions have benefited these patients,
      and this is due to our limited understanding of the host response to injury and
      shock. The Food and Drug Administration requires preclinical animal studies prior
      to any interventional trials in humans; thus, animal models of injury and shock
      will remain the mainstay for trauma research. However, adequate animal models
      that reflect the severe response to trauma in both the acute and subacute phases
      have been limited. Here we describe a novel murine model of polytrauma and shock
      that combines hemorrhagic shock, cecectomy, long bone fracture, and soft-tissue
      damage. This model produces an equivalent Injury Severity Score associated with
      adverse outcomes in humans, and may better recapitulate the human leukocyte,
      cytokine, transcriptomic, and overall inflammatory response following injury and
      hemorrhagic shock.

PMID- 29468580
TI  - Measurement of Intracranial Pressure in Freely Moving Rats.
AB  - Brain injury, such as from stroke and trauma, can be complicated by elevated
      intracranial pressure (ICP). Although raised ICP can be a significant determinant
      of morbidity and mortality, clinical studies often report widely varying ICP
      measurements depending on location of measurement and technique used. For the
      same reasons, reported ICP measurements also vary widely in animal models. The
      need for anesthesia or tethered connections with some methods of ICP measurement
      in animals may introduce additional confounds. Moreover, these methods are not
      well suited for prolonged, continuous measurement. Here, we describe an approach
      to continually measure ICP in awake, freely moving rats for several days. This
      technique uses a commercially available, wireless pressure sensor mounted on the
      head to measure ICP from the epidural space via a fluid-filled catheter. We have
      demonstrated that this approach reliably detects elevations in ICP that last for
      several days after ischemic and hemorrhagic strokes in rat.

PMID- 29468581
TI  - A Lateral Fluid Percussion Injury Model for Studying Traumatic Brain Injury in
      Rats.
AB  - Traumatic brain injury (TBI) diagnoses have increased in frequency during the
      past decade, becoming a silent epidemic. The pathophysiology of TBI involves
      pathophysiological processes affecting the brain, induced by traumatic
      biomechanical forces resulting in temporary impairment of neurological function.
      Preclinical models have been generated to recapitulate the mechanical,
      neuroinflammatory, and behavioral outcomes observed in the clinical setting. The
      lateral fluid percussion (LFP) model is the most extensively used and well
      characterized model of nonpenetrating and nonischemic TBI. The model is
      reproducible and can be adjusted to produce a mild to moderate and severe injury,
      as reflected by mortality and return of reflexes, by adjusting the amount of
      force applied. The histopathological changes achieved with this model reproduce
      that seen in human TBI including focal contusion in the cortex, with accompanying
      intraparenchymal punctate hemorrhage, followed by inflammation and neuronal
      degeneration. This chapter describes the LFP model, which produces a mixed model
      of focal and diffuse brain injury that progresses over time affecting
      predominantly the cortical parenchyma.

PMID- 29468582
TI  - A Mouse Controlled Cortical Impact Model of Traumatic Brain Injury for Studying
      Blood-Brain Barrier Dysfunctions.
AB  - Traumatic brain injury (TBI) is one of the leading causes of death and disability
      worldwide. It is a silently growing epidemic with multifaceted pathogenesis, and
      current standards of treatments aim to target only the symptoms of the primary
      injury, while there is a tremendous need to explore interventions that can halt
      the progression of the secondary injuries. The use of a reliable animal model to
      study and understand the various aspects the pathobiology of TBI is extremely
      important in therapeutic drug development against TBI-associated complications.
      The controlled cortical impact (CCI) model of TBI described here, uses a
      mechanical impactor to inflict a mechanical injury into the mouse brain. This
      method is a reliable and reproducible approach to inflict mild, moderate or
      severe injuries to the animal for studying TBI-associated blood-brain barrier
      (BBB) dysfunctions, neuronal injuries, brain edema, neurobehavioral changes, etc.
      The present method describes how the CCI model could be utilized for determining
      the BBB dysfunction and hyperpermeability associated with TBI. Blood-brain
      barrier disruption is a hallmark feature of the secondary injury that occur
      following TBI, frequently associated with leakage of fluid and proteins into the
      extravascular space leading to vasogenic edema and elevation of intracranial
      pressure. The method described here focuses on the development of a CCI-based
      mouse model of TBI followed by the evaluation of BBB integrity and permeability
      by intravital microscopy as well as Evans Blue extravasation assay.

PMID- 29468583
TI  - A Rat Model of Hemorrhagic Shock for Studying Vascular Hyperpermeability.
AB  - Vascular hyperpermeability is one of the known detrimental effects of hemorrhagic
      shock, which we continually try to understand, minimize, and reverse. Here, we
      describe induction of hemorrhagic shock in a rat and studying of its effects on
      vascular permeability, using intravital microscopy. In this protocol, hemorrhagic
      shock will be induced by withdrawing blood to reduce the mean arterial pressure
      (MAP) to 40 mmHg for 60 min followed by resuscitation for 60 min. To study the
      changes in vascular permeability following hemorrhagic shock, the rats will be
      given FITC-albumin, a fluorescent tracer, intravenously. Following this, the FITC
      albumin flux across the vessel will be measured in mesenteric postcapillary
      venules by determining fluorescent intensity intravascularly and extravascularly
      under intravital microscopy.

PMID- 29468584
TI  - Assessment of Cardiovascular Function and Microvascular Permeability in a
      Conscious Rat Model of Alcohol Intoxication Combined with Hemorrhagic Shock and
      Resuscitation.
AB  - Hypotension, cardiac depression, and elevated microvascular permeability are
      known problems that complicate resuscitation of patients following traumatic
      injury, particularly those who are also intoxicated from alcohol consumption. A
      conscious rat model of combined alcohol intoxication and hemorrhagic shock has
      been used to study the hemodynamic mechanisms involved. Here, we describe using
      this model to study microvascular leakage and cardiac electrical activity.

PMID- 29468585
TI  - Intracerebral Hemorrhage in Mice.
AB  - Intracerebral hemorrhage is the most devastating stroke subtype with high rates
      of mortality and morbidity. Furthermore, no clinically approved treatment exists
      that effectively increases survival or improves quality of life for survivors.
      Effective modeling is necessary to elucidate the pathophysiological mechanisms of
      intracerebral hemorrhage and evaluate potential therapeutic approaches. Rodent
      models are most utilized because of their cost-effectiveness, and because rodent
      brain development and structures are well documented. Herein, we describe two
      intracerebral hemorrhage mouse models: the autologous blood double-injection and
      collagenase infusion models.

PMID- 29468586
TI  - A Rat Burn Injury Model for Studying Changes in Microvascular Permeability.
AB  - The management of burn patients is an extremely complex and clinically
      challenging for patient care. Aside from the increasing reports of burn injury
      and morbidity and mortality directly related to it, the pathobiology of burn
      trauma is not clearly understood. The rat model of burn trauma described here is
      currently used in research laboratories to study various aspects of burn injury,
      including vascular dysfunctions. This model demonstrates the infliction of
      thermal injury in Sprague-Dawley rats using a well-established boiled water
      approach. We have utilized intravital microscopy to examine the microvascular
      hyperpermeability, the excessive leakage of proteins and fluids from the
      intravascular space to the extravascular space in mesenteric postcapillary
      venules using this model. An increase in microvascular permeability is a strong
      indicator of microvascular dysfunctions leading to tissue edema in burn trauma.

PMID- 29468587
TI  - Modeling Transient Focal Ischemic Stroke in Rodents by Intraluminal Filament
      Method of Middle Cerebral Artery Occlusion.
AB  - The middle cerebral artery occlusion (MCAO) model is widely used for inducing a
      focal cerebral ischemic insult (stroke) in rodents. Here, we describe a method
      for transient MCAO technique without craniotomy in both mice and rats. In our
      laboratory, this technique yields consistent secondary brain damage that evolves
      over a period of 3-7 days of reperfusion after transient MCAO. We also describe
      the methods for analyzing postischemic motor dysfunction and infarct volume in
      rodents subjected to transient MCAO.

PMID- 29468588
TI  - A Complete Guide to Using the Endothelin-1 Model of Stroke in Conscious Rats for
      Acute and Long-Term Recovery Studies.
AB  - Multiple methods exist to model permanent and transient ischemia under anesthesia
      in animals, however most human strokes occur while conscious. The use of
      endothelin-1 as a vasoconstrictor applied to the perivascular surface of the
      middle cerebral artery is one of the only methods for inducing stroke in
      conscious animals. Here, we describe standard operating procedures for
      stereotaxic placement of an ET-1 guide probe above the middle cerebral artery,
      induction of stroke in conscious rats, predictive outcome scoring during stroke,
      and neurological behavioral tests that we use to monitor transient and continuing
      deficits. The inclusion of long term neurological assessment is of particular
      importance when taking into consideration the effects of stroke on brain
      remodeling.

PMID- 29468589
TI  - A Murine Model of Hind Limb Ischemia to Study Angiogenesis and Arteriogenesis.
AB  - Therapeutic angiogenesis offers promise as a novel treatment that is
      complementary to surgical or endovascular procedures for peripheral arterial
      diseases (PAD). Appropriate development and use of hind limb ischemia models is
      necessary for successful studies of therapeutic angiogenesis and/or
      arteriogenesis. In this chapter, we describe two commonly used murine unilateral
      hind limb ischemia models, the femoral artery transection model and the
      femoral/saphenous artery excision model.

PMID- 29468590
TI  - A Murine Model of Myocardial Ischemia-Reperfusion Injury.
AB  - Ligation of the left anterior descending (LAD) coronary artery in the mouse heart
      is a widely used model to simulate myocardial infarction and ischemia-reperfusion
      injury. Here we describe a ligation technique routinely performed in our
      laboratory to induce myocardial infarction that may be used to study ischemia
      reperfusion injury in the myocardium. The methods described enhance location of
      the LAD coronary artery to allow for accurate ligation, thus increasing
      reproducibility of infarct size and location.

PMID- 29468591
TI  - A Rat Model of Perinatal Seizures Provoked by Global Hypoxia.
AB  - Hypoxic-ischemic encephalopathy (HIE) refers to acute brain injury that results
      from perinatal asphyxia. HIE is a major cause of neonatal seizures, and outcomes
      can range from apparent recovery to severe cognitive impairment, cerebral palsy,
      and epilepsy. Acute partial seizures frequently aid in indicating the severity
      and localization of brain injury. However, evidence also suggests that the
      occurrence of seizures further increases the likelihood of epilepsy in later life
      regardless of the severity of the initial injury. Here, we describe a neonatal
      rat model of seizure-provoking mild hypoxia without overt brain injury that has
      been used to investigate potential epileptogenic effects of hypoxia-associated
      seizures alone on neonatal brain development. Clinically, HIE is defined by brain
      injury, and thus, this model is not intended to mimic clinical HIE. Rather, its
      utility is in providing a model to understand the dynamic and long-term
      regulation of brain function and how this can be perturbed by early life seizures
      that are provoked by a commonly encountered pathophysiological trigger.
      Additionally, the model allows the study of brain pathophysiology without the
      potential confound of variable neuroanatomical changes that are reactive to
      widespread cell death.

PMID- 29468592
TI  - Experimental Protocol for Cecal Ligation and Puncture Model of Polymicrobial
      Sepsis and Assessment of Vascular Functions in Mice.
AB  - Sepsis is the systemic inflammatory response syndrome that occurs during
      infection and is exacerbated by the inappropriate immune response encountered by
      the affected individual. Despite extensive research, sepsis in humans is one of
      the biggest challenges for clinicians. The high mortality rate in sepsis is
      primarily due to hypoperfusion-induced multiorgan dysfunctions , resulting from a
      marked decrease in peripheral resistance. Vascular dysfunctions are further
      aggravated by sepsis-induced impairment in myocardial contractility. Circulatory
      failure in sepsis is characterized by refractory hypotension and vascular
      hyporeactivity (vasoplegia) to clinically used vasoconstrictors. To investigate
      the complex pathophysiology of sepsis and its associated multiple organ
      dysfunction, several animal models have been developed. However, cecal ligation
      and puncture (CLP) model of murine sepsis is still considered as 'gold standard'
      in sepsis research. In this protocol we have described the standard surgical
      procedure to induce polymicrobial sepsis by cecal ligation and puncture. Further,
      we have described the protocol to study the molecular mechanisms underlying
      vascular dysfunctions in sepsis.

PMID- 29468593
TI  - Methods to Study the Innate Immune Response to Sepsis.
AB  - This chapter describes techniques to measure the innate immune response in the
      mouse cecal ligation and puncture model of sepsis. The reader will learn how to
      perform retro-orbital bleeds to harvest serum from mice and learn how to perform
      peritoneal lavage to harvest cells and inflammatory mediators from this
      compartment. The enzyme-linked immunosorbent assay (ELISA) technique is described
      as a method to measure the levels of cytokines and chemokines in these fluids.
      Additionally, this chapter describes techniques to stain the cellular fraction of
      the peritoneal lavage with fluorescently labeled antibodies, and perform
      fluorescence activated cell sorting (FACS) to quantify macrophages and
      neutrophils in this compartment.

PMID- 29468594
TI  - An Ovine Model for Studying the Pathophysiology of Septic Acute Kidney Injury.
AB  - The development of acute kidney injury (AKI) is both a significant and
      independent prognostic factor of mortality in patients with sepsis, but its
      pathophysiology remains unclear. Herein, we describe an ovine model of sepsis
      evoked by the administration of live Escherichia coli in which there is
      hypotension, peripheral vasodilatation with a large increase in cardiac output; a
      similar hyperdynamic state to that commonly reported in humans. Interestingly, in
      this sheep model of sepsis, despite an increase in global kidney blood flow,
      there is a progressive reduction in renal function. Although renal hyperperfusion
      develops, renal tissue hypoxia due to redistribution of intrarenal blood flow may
      contribute to the pathogenesis of septic AKI. We have, therefore, developed a
      novel methodology to chronically implant combination probes to monitor intrarenal
      tissue perfusion and oxygen tension during the development of septic AKI in
      conscious sheep with hyperdynamic sepsis.

PMID- 29468595
TI  - An In Vitro Model of Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) is a significant problem causing high mortality
      globally. Methods to increase possibilities for treatment and prevention of
      secondary injuries resulting from the initial physical insult are thus much
      needed. TBI affects the central nervous system (CNS) and the neurovascular unit
      as a whole in numerous ways but one of the primarily compromised components is
      the blood-brain barrier (BBB).In this chapter, we present a detailed procedure on
      how stretch injury and oxygen-glucose deprivation (OGD) are applied to brain
      microvascular endothelial cells of the BBB in order to replicate the actual
      impact they receive during TBI.

PMID- 29468596
TI  - An In Vitro Oxygen-Glucose Deprivation Model for Studying Ischemia-Reperfusion
      Injury of Neuronal Cells.
AB  - Ischemia-reperfusion syndromes of the heart and brain are the leading cause of
      death and long-term disability worldwide. Development of effective treatments for
      myocardial infarction, stroke, cardiac arrest and their sequelae requires
      preclinical models that replicate specific features of ischemia-reperfusion. The
      complexities of intact animals, including the integrated function of organ
      systems, autonomic innervation and endocrine factors, often preclude detailed
      study of specific components of ischemia-reperfusion injury cascades. Ischemia
      represents the interruption of metabolic fuel and oxygen delivery to support
      cellular oxidative metabolism; reintroduction of oxygen upon reperfusion of
      ischemic tissue triggers oxidative stress which initiates the reperfusion injury
      cascade culminating in injury and death of cells and tissues. Thus, cultured
      cells subjected to hypoxia, fuel deprivation and reoxygenation replicate the
      cardinal features of ischemia-reperfusion, while accommodating interventions such
      as siRNA suppression of specific genes and pharmacological activation or
      inhibition of signaling cascades that are not feasible in more complex
      preparations, especially intact animals. This chapter describes an in vitro OGD
      reoxygenation cell culture model, an excellent preparation to examine the
      cellular mechanisms mediating ischemia-reperfusion injury and/or cytoprotection.

PMID- 29468597
TI  - Measurement of Microvascular Endothelial Barrier Dysfunction and
      Hyperpermeability In Vitro.
AB  - Loss of microvascular endothelial barrier integrity leads to vascular
      hyperpermeability and vasogenic edema in a variety of disease processes including
      trauma, ischemia and sepsis. Understanding these principles gives valuable
      information on pathophysiology and therapeutic drug development. While animal
      models of traumatic and ischemic injuries are useful to understand vascular
      dysfunctions associated with such injuries, in vitro barrier integrity assays are
      reliable and helpful adjuncts to understand the cellular and molecular changes
      and signaling mechanisms that regulate barrier function. We describe here the
      endothelial monolayer permeability assay and transendothelial electrical
      resistance (TEER) measurement as in vitro methods to test changes in
      microvascular integrity and permeability. These in vitro assays are based on
      either the measurement of electrical resistance of the monolayer or the
      quantitative evaluation of fluorescently tagged molecules (e.g., FITC-dextran)
      that pass through the monolayer when there is damage or breakdown.

PMID- 29468598
TI  - Microbiological analysis and the outcomes of periodontal treatment with or
      without adjunctive systemic antibiotics-a retrospective study.
AB  - OBJECTIVES: The purpose of this retrospective study was to assess the impact of
      microbiological diagnostics on the outcomes of periodontal treatment with or
      without adjunctive use of systemic antibiotics. MATERIALS AND METHODS: Patient
      files were screened for microbiological analysis before (T1) and after non
      surgical periodontal therapy (T2). Medical history, diagnosis, clinical data, and
      results of the microbiological analysis were extracted from the patient's file.
      After descriptive statistics, logistic regression analysis was performed to model
      the presence of 90 and 50% reductions of numbers of sites with probing depths
      (PD) of >= 5 mm at T2 (90%-PD5 and 50%-PD5), respectively, against the presence
      of bacterial species, clinical diagnosis, and adjunctive use of systemic
      antibiotics. RESULTS: Eighteen patients diagnosed with aggressive periodontitis
      (AP, 17 with adjunctive antibiotics) and 84 with chronic periodontitis (CP, 31
      with adjunctive antibiotics) were included in the analysis. Logistic modeling of
      bacteria at T1 to 90%-PD5 failed to show any statistical significance. Using 50%
      PD5, presence of all Porphyromonas gingivalis, Tannerella forsythia, and
      Treponema denticola and in particular of T. denticola at T1 was associated with
      good response to therapy. Modeling of bacterial presence to 90-%PD5 and to 50
      %PD5 at T2 found an association with absence of T. forsythia (90-%PD5 and 50
      %PD5) and of T. denticola and Campylobacter rectus (50%-PD5). Modeling bacteria
      at T1, antibiotic group and oral hygiene at T2 on 50%-PD5 revealed odds ratio
      (OR) of the adjunctive antibiotic group between 2.70 and 52.4, of the oral
      hygiene between 3.27 and 4.11, and of the bacteria at T1 up to 28.6
      (Porphyromonas gingivalis, T. forsythia, or T. denticola). CONCLUSION:
      Microbiological analysis of the most important species associated with
      periodontal diseases appears to support a clinically based decision for the
      adjunctive use of systemic antibiotics. CLINICAL RELEVANCE: The present findings
      appear to support the use microbiological testing to strengthen the clinical
      decision making process for either using or not using systemic antibiotics in
      conjunction with non-surgical periodontal therapy.

PMID- 29468599
TI  - Determination of nicotine content in teeth submitted to prophylaxis and in-office
      bleaching by gas chromatography-mass spectrometry (GC-MS).
AB  - OBJECTIVES: The objective of this study was to evaluate the dental color exposed
      to acute cigarette smoke treatment and quantify the amount of nicotine in samples
      exposed to cigarette smoke, after dental prophylaxis and after in-office
      bleaching. MATERIALS AND METHODS: Sixty-nine healthy human molars were subjected
      to cigarette smoke in a cigarette machine. The teeth were divided into three
      groups: positive control, prophylaxis, and bleaching. Forty cycles of smoke
      exposition with duration of 15 min each were performed using 10 cigarettes
      (positive control). Dental prophylaxis was performed with a rotating brush and
      prophylaxis paste; in-office bleaching was performed with 35% hydrogen peroxide,
      in two sessions of three 15-min applications, with a 1-week interval between
      sessions. The color was evaluated at the baseline, after exposure to cigarette
      smoke, after dental prophylaxis, and after in-office bleaching. Teeth from each
      group were powdered and analyzed by gas chromatography-mass spectrometry in order
      to measure the amount of nicotine present in each group. Data from quantification
      of nicotine and color change were analyzed by one-way ANOVA and Tukey's test
      (alpha = 0.05). Data for subjective and objective color evaluation, a perceptible
      dental darkening occurred in teeth after exposure to cigarette smoke. Dental
      prophylaxis was able to recover the original color of teeth however, only after
      bleaching teeth became whiter than at the baseline (p < 0.001). The amount of
      nicotine was significantly different and higher in positive control group (3.3 +/
      1.3 MUg/g of tooth), followed by the prophylaxis group (2.1 +/- 1.4 MUg/g) and
      the bleaching group (0.8 +/- 0.3 MUg/g) (p < 0.001). CONCLUSIONS: Cigarette smoke
      penetrates into the dental structure. Dental prophylaxis and bleaching with 35%
      hydrogen peroxide can partially remove the nicotine from tobacco smoke. However,
      when in-office bleaching was applied, a more significant nicotine removal was
      achieved. CLINICAL SIGNIFICANCE: Dental prophylaxis could remove most of the
      external nicotine-staining on the tooth surfaces while bleaching could further
      reduce the external and internal nicotine-staining of teeth.

PMID- 29468600
TI  - CAD/CAM produces dentures with improved fit.
AB  - OBJECTIVES: Resin polymerisation shrinkage reduces the congruence of the denture
      base with denture-bearing tissues and thereby decreases the retention of
      conventionally fabricated dentures. CAD/CAM denture manufacturing is a
      subtractive process, and polymerisation shrinkage is not an issue anymore.
      Therefore, CAD/CAM dentures are assumed to show a higher denture base congruence
      than conventionally fabricated dentures. It has been the aim of this study to
      test this hypothesis. MATERIALS AND METHODS: CAD/CAM dentures provided by four
      different manufacturers (AvaDent, Merz Dental, Whole You, Wieland/Ivoclar) were
      generated from ten different master casts. Ten conventional dentures (pack and
      press, long-term heat polymerisation) made from the same master casts served as
      control group. The master casts and all denture bases were scanned and matched
      digitally. The absolute incongruences were measured using a 2-mm mesh. RESULTS:
      Conventionally fabricated dentures showed a mean deviation of 0.105 mm, SD =
      0.019 from the master cast. All CAD/CAM dentures showed lower mean incongruences.
      From all CAD/CAM dentures, AvaDent Digital Dentures showed the highest congruence
      with the master cast surface with a mean deviation of 0.058 mm, SD = 0.005.
      Wieland Digital Dentures showed a mean deviation of 0.068 mm, SD = 0.005, Whole
      You Nexteeth prostheses showed a mean deviation of 0.074 mm, SD = 0.011 and
      Baltic Denture System prostheses showed a mean deviation of 0.086 mm, SD = 0.012.
      CONCLUSIONS: CAD/CAM produces dentures with better fit than conventional
      dentures. CLINICAL RELEVANCE: The present study explains the clinically observed
      enhanced retention and lower traumatic ulcer-frequency in CAD/CAM dentures.

PMID- 29468601
TI  - Patient and Clinician Perspectives on Shared Decision-making in Early Adopting
      Lung Cancer Screening Programs: a Qualitative Study.
AB  - BACKGROUND: Guidelines recommend, and Medicare requires, shared decision-making
      between patients and clinicians before referring individuals at high risk of lung
      cancer for chest CT screening. However, little is known about the extent to which
      shared decision-making about lung cancer screening is achieved in real-world
      settings. OBJECTIVE: To characterize patient and clinician impressions of early
      experiences with communication and decision-making about lung cancer screening
      and perceived barriers to achieving shared decision-making. DESIGN: Qualitative
      study entailing semi-structured interviews and focus groups. PARTICIPANTS: We
      enrolled 36 clinicians who refer patients for lung cancer screening and 49
      patients who had undergone lung cancer screening in the prior year. Participants
      were recruited from lung cancer screening programs at four hospitals (three
      Veterans Health Administration, one urban safety net). APPROACH: Using content
      analysis, we analyzed transcripts to characterize communication and decision
      making about lung cancer screening. Our analysis focused on the recommended
      components of shared decision-making (information sharing, deliberation, and
      decision aid use) and barriers to achieving shared decision-making. KEY RESULTS:
      Clinicians varied in the information shared with patients, and did not
      consistently incorporate decision aids. Clinicians believed they explained the
      rationale and gave some (often purposely limited) information about the trade
      offs of lung cancer screening. By contrast, some patients reported receiving
      little information about screening or its trade-offs and did not realize the CT
      was intended as a screening test for lung cancer. Clinicians and patients alike
      did not perceive that significant deliberation typically occurred. Clinicians
      perceived insufficient time, competing priorities, difficulty accessing decision
      aids, limited patient comprehension, and anticipated patient emotions as barriers
      to realizing shared decision-making. CONCLUSIONS: Due to multiple perceived
      barriers, patient-clinician conversations about lung cancer screening may fall
      short of guideline-recommended shared decision-making supported by a decision
      aid. Consequently, patients may be left uncertain about lung cancer screening's
      rationale, trade-offs, and process.

PMID- 29468602
TI  - Time Series Disturbance Detection for Hypothesis-Free Signal Detection in
      Longitudinal Observational Databases.
AB  - INTRODUCTION: Signal detection remains a cornerstone activity of
      pharmacovigilance. Routine quantitative signal detection primarily focuses on
      screening of spontaneous reports. In striving to enhance quantitative signal
      detection capability further, other data streams are being considered for their
      potential contribution as sources of emerging signals, one of which is
      longitudinal observational databases, including electronic medical record (EMR)
      and transactional insurance claims databases. Quantitative signal detection on
      such databases is a nascent field-with published methods being primarily based
      either on individual metrics, which may not effectively represent the complexity
      of the longitudinal records and their necessary variation for analysis for drug
      outcome pairs, or on visualization discovery approaches leveraging multiple
      aspects of the records, which are not particularly tractable to high-throughput
      hypothesis-free signal detection. One extensively tested example of the latter is
      chronographs. METHODS: We apply a disturbance detection algorithm to chronographs
      using UK EMR The Health Improvement Network (THIN) data. The algorithm utilizes
      autoregressive integrated moving average (ARIMA)-based time series methodology
      designed to find disturbances that occur outside the normal pattern trends of the
      ARIMA model for the chronograph. Chronographs currently highlight drug-event
      pairs as potentially worthy of further clinical assessment, via filter-based
      increases in disproportionality scores from before to after the index drug
      exposure, tested across a range of case and control windows. RESULTS: We
      replicate the findings on six exemplar chronographs from a previous publication,
      and show how disturbances can be effectively detected across this set of pairs.
      Further, 692 disturbances were detected in analysis of all 384 individual READ
      code outcomes ever recorded 50 or more times for patients prescribed sibutramine.
      The disturbances are algorithmically further broken into subsets of clinical
      interest. CONCLUSION: Overall, the disturbance algorithm approach shows promising
      capacity for detecting outliers, and shows tractability of the algorithmic
      approach for large-scale screening. The method offers an array of pattern types
      for detection and clinical review.

PMID- 29468604
TI  - Urinary Diversion After Radical Cystectomy for Bladder Cancer: Comparing Trends
      in the US and Germany from 2006 to 2014.
AB  - OBJECTIVE: Our aim was to assess and compare trends of urinary diversion (UD) for
      patients receiving radical cystectomy for the treatment of bladder cancer in the
      US and Germany, and to investigate decisive predictors for the choice of UD.
      METHODS: We analyzed the nationwide German hospital billing database and the
      Nationwide Inpatient Sample (NIS) from 2006 to 2014. Cases with a bladder cancer
      diagnosis combined with RC were included, and trends in the choice of UD,
      transfusion rates, length of stay, and mortality were assessed. RESULTS: From
      2006 to 2014, the total number of RCs recorded within the NIS were 17,711, with a
      varying annual caseload of 1666-2009, while RC numbers increased from 5627 to
      7390 in Germany (p < 0.001 for trends), with a total of 60,447 cases. The share
      of incontinent UD in the US remained stable at 93%, while increasing from 63.2 to
      70.8% in Germany. Multivariate models indicated age and sex were the most
      important factors associated with the choice of UD in both countries, while
      hospital caseload and teaching status were less relevant factors in the US. In
      hospital mortality was lower in the US compared with Germany (1.9% vs. 4.6%; p <
      0.001), with significantly shorter hospital stays (10.7 days in the US vs. 25.1
      days in Germany; p < 0.001). CONCLUSIONS: The increasing age of patients with
      presumably higher comorbidity in recent years led to increased use of incontinent
      UD in Germany, while continent UD appears to be underused in the US. Mortality
      and transfusion rates were significantly lower in the US within a shorter
      hospital stay.

PMID- 29468603
TI  - Glucocorticoids and the Risk of Peptic Ulcer Bleeding: Case-Control Analysis
      Based on Swiss Claims Data.
AB  - INTRODUCTION: Controversy exists as to whether glucocorticoids (GC) are
      ulcerogenic per se and may thus cause peptic ulcer bleeding (PUB) independent of
      concomitantly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs).
      OBJECTIVE: To investigate the association between GC use and PUB with or without
      co-medication with NSAIDs. METHODS: We conducted a case-control study using
      administrative claims data from the Swiss health insurance company Helsana. We
      identified 1191 cases with incident PUB between 2012 and 2016 and matched up to
      10 PUB-free controls to each case on age, sex, region and number of years insured
      with Helsana. We compared prior GC exposure between cases and controls using
      multivariate conditional logistic regression analyses controlling for several
      potential confounders. Patients with or without concomitant NSAID exposure were
      analysed separately. RESULTS: Patients with prior exposure to both GC and NSAIDs
      were five times more likely to experience PUB than patients who neither used GC
      nor NSAIDs (adjusted odds ratio [adj. OR] 4.80, 95% CI 3.55-6.71). Although the
      risk of PUB among patients who used NSAIDs without GC was increased threefold
      (adj. OR 3.20, 95% CI 2.59-3.95), we observed only a moderately increased risk
      among patients who used GC alone without NSAIDs (adj. OR 1.63, 95% CI 1.20-2.42).
      CONCLUSIONS: The use of NSAIDs with or without GC was associated with a markedly
      higher risk of PUB compared with GC monotherapy. Use of GC alone was associated
      with a moderately increased risk of PUB, which might be causal or attributed to
      confounding by indication.

PMID- 29468605
TI  - Minimally Invasive Liver Surgery: Has it Achieved the Standard of Care?

PMID- 29468606
TI  - Repeat Sentinel Lymph Node Biopsy for Ipsilateral Breast Tumor Recurrence: A
      Systematic Review of the Results and Impact on Prognosis.
AB  - BACKGROUND: During recent years, an increasing number of patients with
      ipsilateral breast tumor recurrence (IBTR) and previous axillary surgery have
      undergone repeat sentinel lymph node biopsy (rSLNB). The influence of axillary
      nodal status on prognosis for IBTR patients remains unclear. This study aimed to
      evaluate the technical success rate, follow-up assessment, and prognostic value
      of rSLNB for patients with IBTR. METHODS: A systematic search conducted in
      MEDLINE, Embase, and the Cochrane Library up to July 2017 included all studies on
      rSLNB in IBTR. RESULTS: A total of 34 articles describing 1761 patients were
      identified. A repeat sentinel lymph node (rSLN) was successfully harvested from
      64.3% of the patients with IBTR, and the rate was significantly higher for the
      patients who had a previous SLNB than for those who had a previous axillary lymph
      node dissection (ALND) (75.7% vs. 46.1%; P < 0.0001). The rSLN was tumor-positive
      for 18.2% of the rSLNs, 40% of which were harvested in basins other than the
      ipsilateral axilla. The negative predictive value of the rSLNB was 96.5%. Overall
      survival, reported for 21.5% of the patients, was 95.2% after a mean follow-up
      period of 29.6 months. CONCLUSION: The prognostic impact of rSLN-positive versus
      rSLN-negative IBTR remains unclear. Further studies are needed to fill in the gap
      in the management of lymph nodes for patients with IBTR. However, based on the
      current evidence, rSLNB is feasible for 64% of patients, especially after
      previous SLNB. With a negative predictive value of 96.5%, rSLNB appears to be
      highly specific, with substantial advantages over ipsilateral ALND in IBTR.

PMID- 29468607
TI  - The Patient-Reported Information Multidimensional Exploration (PRIME) Framework
      for Investigating Emotions and Other Factors of Prostate Cancer Patients with Low
      Intermediate Risk Based on Online Cancer Support Group Discussions.
AB  - BACKGROUND: This study aimed to use the Patient Reported Information
      Multidimensional Exploration (PRIME) framework, a novel ensemble of machine
      learning and deep-learning algorithms, to extract, analyze, and correlate self
      reported information from Online Cancer Support Groups (OCSG) by patients (and
      partners of patients) with low intermediate-risk prostate cancer (PCa) undergoing
      radical prostatectomy (RP), external beam radiotherapy (EBRT), and active
      surveillance (AS), and to investigate its efficacy in quality-of-life (QoL) and
      emotion measures. METHODS: From patient-reported information on 10 OCSG, the
      PRIME framework automatically filtered and extracted conversations on low
      intermediate-risk PCa with active user participation. Side effects as well as
      emotional and QoL outcomes for 6084 patients were analyzed. RESULTS: Side-effect
      profiles differed between the methods analyzed, with men after RP having more
      urinary and sexual side effects and men after EBRT having more bowel symptoms.
      Key findings from the analysis of emotional expressions showed that PCa patients
      younger than 40 years expressed significantly high positive and negative emotions
      compared with other age groups, that partners of patients expressed more negative
      emotions than the patients, and that selected cohorts (< 40 years, > 70 years,
      partners of patients) have frequently used the same terms to express their
      emotions, which is indicative of QoL issues specific to those cohorts.
      CONCLUSION: Despite recent advances in patient-centerd care, patient emotions are
      largely overlooked, especially in younger men with a diagnosis of PCa and their
      partners. The authors present a novel approach, the PRIME framework, to extract,
      analyze, and correlate key patient factors. This framework improves understanding
      of QoL and identifies low intermediate-risk PCa patients who require additional
      support.

PMID- 29468608
TI  - Adjuvant Therapy in the Treatment of Melanoma.

PMID- 29468609
TI  - Comparative Performance of the 7th and 8th Editions of the American Joint
      Committee on Cancer Staging Systems for Soft Tissue Sarcoma of the Trunk and
      Extremities.
AB  - BACKGROUND: The 8th edition American Joint Committee on Cancer (AJCC) staging for
      soft tissue sarcomas of the trunk/extremities divides T stage into four
      categories and upstages nodal disease to stage IV. We used the National Cancer
      Database (NCDB) to evaluate the prognostic power of the new system. METHODS: A
      total of 26,144 patients were identified from the NCDB from 2004 to 2013. Overall
      survival (OS) was compared using Kaplan-Meier and Cox proportional hazard models.
      RESULTS: Including T3 (10 cm > * >15 cm) and T4 (> 15 cm) categories resulted in
      an increased number of patients classified as stage III (5120 as IIIA [19.6%] and
      4280 as IIIB [16.4%], vs. 7882 [30.1%] previously), and there was a small
      increase in the number of patients classified as stage IV (2776 [10.6%], vs. 2565
      [9.8%] previously). In the 7th edition, the hazard ratio (HR) for death increases
      with stage, with large incremental increases between stages II-III and III-IV. In
      the 8th edition, the HR for death demonstrates smaller incremental increases
      between each stage. Five-year OS for 7th edition T1 and T2 patients was 78.8 and
      58.8% (p < 0.01), respectively, versus 62.6, 53.5, and 56.1% for T2, T3, and T4
      patients, respectively, in the 8th edition (p < 0.01). Patients with isolated
      nodal disease (n = 211) had a better 5-year OS than those with distant metastases
      (33.1% vs. 12.4%, p < 0.001). CONCLUSIONS: The AJCC 8th edition uses T stage to
      more accurately stratify OS in patients with large, high-grade tumors (T3/4)
      compared with those patients with T2 tumors, which facilitates risk assessment.
      The distinction between T3 and T4 may not be clinically significant. Patients
      with metastatic nodal disease have a survival outcome intermediate to those with
      stages III and IV disease.

PMID- 29468610
TI  - Denis Parsons Burkitt, an Overlooked Surgical Oncologist.

PMID- 29468611
TI  - Influences of Copper/Zinc-Loaded Montmorillonite on Growth Performance, Mineral
      Retention, Intestinal Morphology, Mucosa Antioxidant Capacity, and Cytokine
      Contents in Weaned Piglets.
AB  - The effects of copper/zinc-loaded montmorillonite (Cu/Zn-Mt) on growth
      performance, mineral retention, intestinal morphology, mucosa antioxidant
      capacity, and cytokine contents in weaned piglets were investigated in the
      present study. One hundred eight piglets weaned at 21 +/- 1 days of age (Duroc *
      Landrace* Yorkshire; average initial weight of 6.36 kg) were allotted to three
      treatments for 2 weeks. The three treatments were as follows: (1) control group:
      basal diet; (2) Cu/Zn-Mt group: basal diet + 39 mg/kg Cu and 75 mg/kg Zn as Cu/Zn
      Mt; (3) Cu + Zn + Mt group: basal diet + mixture of CuSO4, ZnSO4, and Mt (equal
      amount of Cu, Zn, and Mt to the Cu/Zn-Mt group). Each treatment had six pens of
      six piglets. The results showed that as compared with the control group and the
      Cu + Zn + Mt group, Cu/Zn-Mt supplementation increased (P < 0.05) the average
      daily gain and the gain/feed ratio; Cu/Zn-Mt supplementation increased (P < 0.05)
      the Cu and Zn concentrations in serum, jejunum, and ileum mucosa, villus height,
      the ratio of villus height to crypt depth, and the activities of SOD, GSH-Px, and
      IL-10 levels, and decreased the malondialdehyde concentrations in the jejunum and
      ileum, and intestinal IL-1beta, IL-6, and TNF-alpha levels. Moreover,
      supplementation with the mixture of CuSO4, ZnSO4, and Mt had no effect on the
      growth performance, but increased the mucosa Cu and Zn concentrations, intestinal
      morphology, antioxidant capacity, and immune function in the duodenum, while it
      had no effect on the above indexes in the jejunum and ileum. The results
      indicated that Mt could be used as a controlled carrier for Cu and Zn, which made
      Cu/Zn-Mt have better biological activities in the intestine than the mixture of
      Cu, Zn, and Mt.

PMID- 29468612
TI  - Selenium-Enriched Saccharomyces cerevisiae Reduces the Progression of Colorectal
      Cancer.
AB  - Colorectal cancer is one of the most common causes of mortality in the world
      while malnutrition is responsible for one third of the problem. Selenium has been
      recommended for prevention of colorectal cancer. The present study was conducted
      to investigate the effect of selenium-enriched Saccharomyces cerevisiae in
      reducing colorectal cancer progression in rats. Five groups of 170-200-g weight
      rats (n = 40) including healthy and cancer controls, Saccharomyces cerevisiae,
      selenium, and selenium-enriched Saccharomyces cerevisiae-treated groups were
      examined. All animals except healthy control group received 40 mg 1,2
      dimethylhydrazine (DMH) per kilogram weight of rat twice a week. The healthy
      group received normal saline, and synchronously, selenium group received soluble
      selenium (4 mg/mL), Saccharomyces cerevisiae and selenium-enriched groups
      received yeast with the density of 5 * 108 CFU/mL by daily gavage. All treatments
      were carried out for 5 weeks after the last injection. Animals were autopsied,
      and aberrant crypt foci (ACF) of ejected colon were studied in the 40th week.
      Microscopic sections were prepared for hematoxylin and eosin. Furthermore,
      immunohistochemical staining of CD31, BCL2, and P53 antibodies was performed.
      Macroscopic and microscopic evaluations showed that DMH had the least destructive
      effect in selenium-enriched Saccharomyces cerevisiae group compared to other
      groups. Selenium-enriched Saccharomyces cerevisiae reduces colorectal cancer
      progression by various mechanisms such as reduction in the number and size of ACF
      and alteration in the function of the proteins such as P53, BCL2, and CD31.

PMID- 29468613
TI  - Effects of Dietary Zinc Oxide Nanoparticles on Growth, Diarrhea, Mineral
      Deposition, Intestinal Morphology, and Barrier of Weaned Piglets.
AB  - This study was conducted to investigate effects of dietary zinc oxide
      nanoparticles (nano-ZnOs) on growth, diarrhea rate, mineral deposition (Zn, Fe,
      and Mn), intestinal morphology, and barrier of weaned piglets. A total of 384
      weaned piglets (Duroc * Landrace * Yorkshire) in 4 groups were fed a basal diet
      supplemented with 0, 400, and 800 mg/kg nano-ZnOs or 3000 mg/kg ZnO for 14 days.
      Compared with the control group, 800 mg/kg nano-ZnOs and 3000 mg/kg ZnO
      significantly increased average daily gain and decreased diarrhea rate of weaned
      piglets. There was no significant difference among ZnO and nano-ZnO groups. ZnO
      and nano-ZnOs did not affect serum activities of glutamic oxalacetic
      transaminase, glutamic-pyruvic transaminase, and lactate dehydrogenase. However,
      ZnO and 800 mg/kg nano-ZnOs significantly increased zinc concentrations in
      plasma, liver, pancreas, and tibia, without affecting Fe and Mn concentrations.
      Compared with the control group, 800 mg/kg nano-ZnOs significantly reduced plasma
      diamine oxidase activity, decreased total aerobic bacterial population in
      mesenteric lymph node, enhanced mRNA expressions of occludin, ZO-1, IL-1beta, IL
      10, TNF-alpha, and ki67 in ileal mucosa, and increased villous height, width,
      crypt depth, and surface area. Compared to ZnO group, 800 mg/kg nano-ZnOs
      significantly decreased aerobic bacterial population, enhanced mRNA expressions
      of occludin, IL-1beta, IL-10, and TNF-alpha, and reduced fecal zinc
      concentration. These results indicated that 800 mg/kg nano-ZnOs might be a
      potential substitute for 3000 mg/kg ZnO in diets of weaned piglets.

PMID- 29468614
TI  - Association of the CAN score with the FRAIL scale in community dwelling older
      adults.
AB  - BACKGROUND: Frailty is a state of vulnerability to stressors which results in
      higher morbidity, mortality and healthcare utilization. The FRAIL scale is used
      as a validated screening for frailty. The Care Assessment Need (CAN) score is
      automatically generated from electronic health record data using a statistical
      model that includes data elements similar to the deficit accumulation model for
      frailty and predicts risk for hospitalization and/or mortality. AIM: To determine
      the correlation of the CAN score with the FRAIL scale. METHODS: A cross-sectional
      study of 503 community-dwelling older adults. We compared the FRAIL scale with
      the CAN score. RESULTS: The CAN score was significantly different between robust,
      prefrail and frail. Post hoc analysis revealed significant increases in scores
      from robust to prefrail and frail groups, in that order. The CAN score and FRAIL
      scale showed a correlation. CONCLUSIONS: The CAN score show a moderate positive
      association with the FRAIL scale.

PMID- 29468615
TI  - Acute care hospital at different levels of intensity: the role of Geriatrician.
AB  - The traditional model of care is based on "disease-centered" management that
      requires the organization of the hospital in specialized wards, to which the
      patient is assigned for the main disease. The growing need to optimize economical
      and human resources and to promote a global approach to the patient has led to
      the setting up of the intensity of care model. It is a health system based on a
      "patient-centered" approach, where the hospital is organized in departments
      dedicated to patients with homogenous needs of care. In Italy, intensity of care
      model is currently being tested in the hospital organization, where three levels
      of intensity are proposed: low, medium and high. The purpose of the following
      review is to describe the role and importance of the Geriatrician in each of
      these care settings and to highlight the contradiction of a National Health
      System which promotes the geriatric approach to all types of patients, but does
      not invest in the formation and integration of the figure of the Geriatrician in
      clinical practice, condemning it to marginalization or even extinction.

PMID- 29468616
TI  - Does focal mechanical stimulation of the lower limb muscles improve postural
      control and sit to stand movement in elderly?
AB  - BACKGROUNDS: Imbalance in elderly is a common problem strictly related to fall.
      AIMS: This study investigates the possibility that a new protocol based on the
      focal mechanical muscle vibration may improve balance and stability in elderly.
      METHODS: Pre-post non-randomized clinical trial has been used. Patients referring
      postural disequilibrium with negative vestibular bed-side examinations have been
      treated with focal muscle vibration applied to quadriceps muscles and evaluated
      before and immediately after therapy and after 1 week and after 1 month with
      postural stabilometric examination and with an inertial measurement units during
      the time up and go test. RESULTS: Stabilometric analysis showed statistically
      significant differences in both the area (p = 0.01) and sway (p < 0.01) of the
      center of pressure during the close eyes tests. Moreover, the global time of the
      time up and go test was reduced (p < 0.05) and the rotation velocity was
      increased (p < 0.01). CONCLUSIONS: The findings confirm the beneficial role of
      focal muscle vibration in elderly patients improve postural stability and
      mobility.

PMID- 29468617
TI  - Diacerein-containing products: same risk of diarrhoea?

PMID- 29468618
TI  - Analysis of Clinical and Metabolic Profile of Acute Neuromuscular Weakness
      Related to Hypokalemia.
AB  - OBJECTIVE: Acute neuromuscular weakness related to hypokalemia is a readily
      treatable disorder associated with diverse aetiologies. In this study we aim to
      report clinical pattern and biochemical features to identify the different
      aetiologies of the hypokalemic neuromuscular weakness. METHODS: Retrospective
      reviews of the medical record were analysed. Evaluation included demography,
      clinical features, investigations performed to ascertain the aetiologies. All the
      patients were categorised in to 3 groups; Idiopathic hypokalemic paralysis (IHP),
      dengue associated hypokalemic paralysis (DHP) and secondary group (SG) which
      included renal tubular acidosis (RTA- 1 and 2), thyrotoxic periodic paralysis
      (TPP) and Gitelman's syndrome (GS). RESULTS: Forty patients were analysed and the
      mean age was 31.78 (range, 14-60) years and 35 (87.5%) were male.The underlying
      aetiologies comprised of IHP in 20, DHP in 12, RTA-2 in 4, RTA-1 in 2, TPP, GS in
      one each. Weakness on Medical Research Council (MRC) grade was 2.6+/-1.19 (range
      0-4). Comparison of various clinical and laboratory parameters revealed that more
      patient in IHP and SG had recurrent attack (p=0.001). DHP group had low platelet
      (p=0.001), high creatine phosphokinase (CPK) (p=0.01) and serum glutamic
      oxaloacetic transaminase (SGOT) (p=0.008). SG had significantly lower serum
      potassium (p=0.04) and more time to improve (p=0.02). Recovery time correlated
      negatively with serum potassium (r=-0.44, p=0.004) and grade of weakness (r=
      0.42,p=0.007). CONCLUSION: In half of the patients, secondary causes were
      identified. After IHP, the DHP emerged as second common cause in post monsoon
      season. SG had significantly lower serum potassium, recurrent attack and more
      time to improve.

PMID- 29468619
TI  - Outcome of Myasthenia gravis treated with high-dose prednisolone and
      azathioprine: A single centre ambispective study from India.
AB  - PURPOSE: Myasthenia gravis (MG) is treated with many disease modifying therapies,
      namely corticosteroids, thymectomy and immunosuppressants, alone or in various
      combinations. But still, till today no consensus over the optimum therapy for MG
      has been made. METHODS: Out of total 101 patients with MG, 37 patients fulfilled
      the inclusion criteria and in them we ambispectively studied factors affecting
      the outcome in MG treated, to induce leukopenia, with prednisolone (PSL) plus
      azathioprine(AZA), from January 1993 through July 2014. Patients were grouped
      according to the outcome: pharmacological remission (PR), complete stable
      remission (CSR), non-remitter and remitters with or without relapse. Their
      demographic characteristics, MGFA Class, dose of PSL and AZA, time to achieve
      remission, duration of remission, leukocyte counts, thymus status, follow-up
      duration, results of repetitive nerve stimulation, and side effects profile were
      compared. RESULTS: Total 81% patients remitted; PR (83%) was commoner than CSR
      (p=0.003). Factors favoring remission were early onset disease, therapeutic
      leukopenia (p=0.003) and longer follow-up (OR5, p=0.08); those associated with
      relapse were abnormal thymus (CI-1.1-3.4; p=0.09), MGFA class IIb (CI 0.9-3;
      p=0.09) and male gender. Side effects occurred in 48%. CONCLUSION: Aggressive
      therapy with prednisolone plus azathioprine induces remission in a high
      percentage of patients with generalized MG.

PMID- 29468620
TI  - Malnutrition in Acute Stroke Patients Stratified by Stroke Severity- A Hospital
      Based Study.
AB  - BACKGROUND: Stroke results in high mortality with tremendous health care burden.
      Malnutrition is frequently observed in patients after stroke. This study was
      designed to explore the nutritional status in the acute stage of stroke aiming at
      exploring factors related to malnutrition after stroke. METHODS: This was a
      hospital based, prospective, observational study recruiting cerebrovascular
      diseases patients hospitalized for acute management. Patients suffered from all
      kinds of cerebrovascular diseases hospitalized for management within 30 days
      after onset were consecutively recruited in the study hospitals. Stroke severity
      was evaluated by National Institutes of Health Stroke Scale, functional status by
      Barthel index, and global outcome by modified Rankin Scale. Cognitive function
      was evaluated by Mini-Mental State Examination. Nutritional status was assessed
      by Mini Nutritional Assessment (MNA), stratified by 1) adequate nutritional
      status, MNA >= 24; 2) protein-calorie malnutrition, MNA less than 17; 3) at risk
      of malnutrition, MNA between 17 and 23.5. RESULTS: There were 231 cerebral
      infarction patients recruited at 13.5 days (25-75%: 5.0-17.0) after stroke onset
      with mild stroke severity 71.4% and severe 10.4% with nasogastric tube insertion
      in 14%. Malnutrition was identified in 12.1% with 54.1% at risk of malnutrition.
      Factor related to malnutrition was severe stroke severity with dependency.
      Patients with old age, hypertension, and diabetes mellitus tended to have
      malnutrition or risk of malnutrition. CONCLUSION: Nutritional status was poor in
      stroke patients across all stroke severities within weeks. Further longitudinal
      outcome studies to identify the poor outcome and the evolution of nutritional
      status are warranted.

PMID- 29468621
TI  - Fusarium Brain Abscess in a Patient with Diabetes Mellitus and Liver Cirrhosis.
AB  - PURPOSE: Invasive mycosis caused by the Aspergillus, Fusarium, and Mucor can be
      fetal, especially in the immunocompromised patients with central nervous system
      (CNS) involvement. Here we present a case of CNS Fusarium infection, and this is
      the first reported case of Fusarium brain abscess in Taiwan. CASE REPORT: A 65
      year-old woman presented with fever and conscious disturbance for 3 days.
      Neurological examination showed stupor consciousness, neck stiffness, multiple
      cranial nerves palsy, and bilateral Babinski signs. Magnetic resonance imaging
      showed multifocal lesions involving medulla oblongata, pons, bilateral cerebral
      peduncles, and bilateral cerebellar peduncles. Cerebrospinal fluid (CSF) study
      revealed neutrophil predominant pleocytosis, but both blood and CSF culture were
      negative. We treated patient with ceftriaxone and vancomycin initially as empiric
      therapy for suspected bacterial meningoencephalitis. However, chronic sinusitis
      with fungal ball and brain abscess were later found. Despite antifungal treatment
      and surgical intervention, patient expired 3 months after admission. Fungal
      culture of the brain abscess disclosed Fusarium species 2 weeks after her death.
      CONCLUSION: CNS Fusarium infection should be considered when an immunocompromised
      patient presenting with fever, conscious change, cranial nerve palsies, and
      angioinvasion suggested by brain imaging. To properly manage the disease, early
      effective antifungal therapy and neurosurgical intervention are important.

PMID- 29468622
TI  - Diagnosis of Chronic Leptomeningitis by Using Meningeal Biopsy: A Case Report of
      Tuberculous Meningitis.

PMID- 29468623
TI  - Isolated Basilar Artery Dissection with Ischemic Stroke: Report of 4 Cases.
AB  - PURPOSE: Isolated basilar artery dissection (BAD) is a rare cause of ischemic
      stroke. Since the clinical presentations and imaging findings could be non
      specific and subtle, the diagnosis may be difficult. Here, we presented four
      cases of isolated BAD with acute ischemic stroke. CASE REPORT: Four patients
      (age, 22 to 57 years) experienced acute onset of hemiparesis and/or vertigo with
      half of them having initial headache. Acute infarct was noted at pons or
      thalamus. Three cases needed more than one imaging modality or serial follow-up
      imaging to confirm a diagnosis of isolated BAD. Vascular tapering and/or false
      lumen restrictive to basilar artery were the commonest imaging findings. Three of
      our patients received anticoagulant without recurrent infarct or hemorrhagic
      complication. All of the patients had good functional outcome with modified
      Ranking scale scoring 1. CONCLUSION: Isolated BAD may cause variable clinical
      manifestations and the outcome can be favorable. Application of different and
      advanced imaging studies with serial image follow-up are useful to confirm the
      diagnosis.

PMID- 29468624
TI  - Factors associated with preparedness of the US healthcare system to respond to a
      pediatric surge during an infectious disease pandemic: Is our nation prepared?
AB  - OBJECTIVE: Recent incidents have demonstrated that the US health system is
      unprepared for infectious pandemics resulting in a pediatric surge. Development
      of efficient plans and a structured and coordinated regional response to
      pediatric pandemic surge remains an opportunity. To address this gap, we
      conducted a literature review to assess current efforts, propose a response plan
      structure, and recommend policy actions. DESIGN: A literature review, utilizing
      MEDLINE and PubMed, through March 2017 identified articles regarding infectious
      disease pandemics affecting the US pediatric population. After review of current
      literature, a proposed response plan structure for a pediatric pandemic surge was
      designed. RESULTS: Inclusion and exclusion criteria reduced an initial screening
      of 1,787 articles to 162 articles. Articles ranged in their discussion of
      pediatric pandemic surge. Review of the articles led to the proposal of
      organizing the results according to 4 S's; (1) Structure, (2) Staff, (3) Stuff
      (Resources), and (4) Space. CONCLUSION: The review has supported the concern that
      the US health system is unprepared for a pediatric surge induced by infectious
      disease pandemics. Common themes suggest that response plans should reflect the
      4Ss and national guidelines must be translated into regional response systems
      that account for local nuances.

PMID- 29468625
TI  - Analysis of the antidote requirements and outcomes of different radionuclide
      decorporation strategies for a scenario of a "dirty bomb" attack.
AB  - OBJECTIVE: In radiological emergencies, there is a risk of radionuclide
      incorporation. The radiological doses absorbed can be reduced by decorporation
      treatment. Antidote requirements depend on the scenario and treatment strategy
      ("urgent approach": immediate treatment of all patients with possible
      incorporation; "precautionary approach": treatment only after confirmation of
      incorporation). We calculated the number of daily antidote doses for different
      scenarios and the differences in outcome for both treatment strategies. DESIGN:
      The number of potentially contaminated victims was varied from 1,000 to 60,000 (a
      maximum that might seem plausible for "dirty bomb" scenarios in Germany), the
      proportion of patients actually needing decorporation treatment from 0.1 percent
      to 100 percent, the radioactive screening capacities from 250 to 2,500 people/day
      and treatment duration from 10 to 90 days. The outcomes were assessed as total
      statistical lifetime saved assuming an inhalation of 1 mCi cesium-137 and the
      achievable dose reductions by a Prussian Blue treatment. RESULTS: Assuming 1
      percent of the potentially contaminated people actually needing treatment,
      applying an "urgent approach" the requirements for 1,000 victims range from 1,100
      to 3,400 and for 60,000 victims from 489,000 to 4,400,000 daily doses, depending
      on treatment duration and screening capacities. The "urgent approach" is
      associated with larger stockpile requirements than the "precautionary approach",
      up to several hundred times in large-scale scenarios if the proportion of people
      actually needing treatment is low. The impact of the screening capacities is
      particularly important in large-scale scenarios, a low proportion of people
      needing treatment and extended treatment duration. The outcome is better for an
      "urgent approach" particularly in large-scale scenarios and low screening
      capacities. CONCLUSIONS: If only a small fraction of the victims actually needs
      treatment, their timely identification by enhancing screening capacities may be
      the most efficacious way to reduce antidote requirements. In large-scale
      scenarios, it might be necessary to abandon the medically preferable "urgent
      approach" for an antidote-sparing "precautionary approach".

PMID- 29468626
TI  - Deployment of field hospitals to disaster regions: Insights from ten medical
      relief operations spanning three decades.
AB  - OBJECTIVE: The Israeli Defense Force (IDF) Medical Corps developed a model of
      airborne field hospital. This model was structured to deal with disaster
      settings, requiring self-sufficiency, innovation and flexible operative mode in
      the setup of large margins of uncertainty regarding the disaster environment. The
      current study is aimed to critically analyze the experience, gathered in ten such
      missions worldwide. METHODS: Interviews with physicians who actively participated
      in the missions from 1988 until 2015 as chief medical officers combined with
      literature review of principal medical and auxiliary publications in order to
      assess and integrate information about the assembly of these missions. RESULTS: A
      body of knowledge was accumulated over the years by the IDF Medical Corps from
      deploying numerous relief missions to both natural (earthquake, typhoon, and
      tsunami), and man-made disasters, occurring in nine countries (Armenia, Rwanda,
      Kosovo, Turkey, India, Haiti, Japan, Philippines, and Nepal). This study shows an
      evolutionary pattern with improvements implemented from one mission to the other,
      with special adaptations (creativity and improvisation) to accommodate logistics
      barriers. CONCLUSION: The principals and operative function for deploying medical
      relief system, proposed over 20 years ago, were challenged and validated in the
      subsequent missions of IDF outlined in the current study. These principals, with
      the advantage of the military infrastructure and the expertise of drafted
      civilian medical professionals enable the rapid assembly and allocation of highly
      competent medical facilities in disaster settings. This structure model is to
      large extent self-sufficient with a substantial operative flexibility that
      permits early deployment upon request while the disaster assessment and
      definition of needs are preliminary.

PMID- 29468627
TI  - Terrorism reports: The tip of the iceberg.
AB  - IMPORTANCE: Medical impact of terror is a public health issue as the threat is
      growing all over the world. OBJECTIVE: Our objective was to compare the number of
      injured and incidents in the three different databases and reports [Global
      Terrorism Database (GTD), Israeli Security Agency (ISA) and National Insurance
      Institute (NII)] in Israel. DESIGN: Retrospective study. SETTING: Analyses of
      three different databases (GTD, ISA and NII) and basic comparison. MAIN
      OUTCOME(S) AND MEASURE(S): The victims reimbursed for medical expenses are the
      largest population. The number of injured as described by GTD and ISA database
      are less important. The 2010-2013 years are marked by more incidents recognized
      in Israel vs GTD assessment (except in 2014). CONCLUSIONS AND RELEVANCE: The
      number of victims being reimbursed for medical and mental health services is
      radically different from the GTD and the ISA reports. Public Health specialists
      should be advised of this phenomenon to deliver their right approach (including
      mental health) to growing threat and develop new definition of victim of terror.

PMID- 29468628
TI  - Acceptability and perceived utility of drone technology among emergency medical
      service responders and incident commanders for mass casualty incident management.
AB  - OBJECTIVE: This study seeks to understand the acceptability and perceived utility
      of unmanned aerial vehicle (UAV) technology to Mass Casualty Incidents (MCI)
      scene management. DESIGN: Qualitative questionnaires regarding the ease of
      operation, perceived usefulness, and training time to operate UAVs were
      administered to Emergency Medical Technicians (n = 15). SETTING: A Single Urban
      New England Academic Tertiary Care Medical Center. PARTICIPANTS: Front-line
      emergency medical service (EMS) providers and senior EMS personnel in Incident
      Commander roles. CONCLUSIONS: Data from this pilot study indicate that EMS
      responders are accepting to deploying and operating UAV technology in a disaster
      scenario. Additionally, they perceived UAV technology as easy to adopt yet
      impactful in improving MCI scene management.

PMID- 29468629
TI  - Emergency operations program is an excellent platform to deal with in-hospital
      operation disaster.
AB  - Described herein is the utilization of the hospital's Emergency Operations Plan
      and incident command structure to mitigate damage caused by the sudden loss of
      the heating, ventilation, and air conditioning system within the entire operating
      room suite. The ability to ameliorate a devastating situation that occurred
      during working hours at a busy Level II trauma center can be ascribed to the
      dedication of the leadership and clinical teams working seamlessly together.
      Their concerted efforts were augmented by adherence to an established protocol
      that had been thoroughly substantiated and practiced during numerous training
      simulations. This resulted in successful and timely resolution of an internal
      crisis that crippled the surgical capabilities of the sole trauma center in the
      county. After thorough investigation and identification of the issues that
      contributed to the malfunction, redundancies were built into the system to ensure
      that a similar incident did not occur again.

PMID- 29468630
TI  - A blueberry muffin rash at birth.

PMID- 29468631
TI  - High-dose melphalan-based sequential conditioning chemotherapy followed by
      allogeneic haematopoietic stem cell transplantation in adult patients with
      relapsed or refractory acute myeloid leukaemia.
AB  - Considering the unsatisfactory results of salvage therapies for patients with
      relapsed/refractory acute myeloid leukaemia (R/R-AML), their value before
      allogeneic haematopoietic stem cell transplantation (HSCT) remains questionable.
      However, direct allogeneic HSCT following established conditioning regimens
      applied in patients with R/R-AML during active disease has been equally
      disappointing. In this retrospective observational study, high-dose melphalan, as
      part of a sequential preparative regimen, followed by a total body irradiation (4
      * 2 Gy)-based or a treosulfan-based dose-adapted conditioning therapy for
      allogeneic HSCT was administered to 292 adult patients (median age 56 years,
      range 17-74) with primary refractory (144 patients), secondary refractory (97
      patients) or relapsed AML (51 patients). Overall survival rates at 3 years were
      34%, 29% and 41%, respectively. Risk factors associated with an inferior survival
      were higher age, transplantation from a human leucocyte antigen-mismatched donor
      and high disease burden. Patients transplanted with blast infiltration <20%
      showed a notable survival rate of 51% at 3 years. In particular, patients with
      primary refractory AML showed a more favourable outcome when transplanted early
      during their disease course. Thus, high-dose melphalan-based sequential
      conditioning chemotherapy followed by an allogeneic HSCT is feasible and enables
      long-term remission to be achieved in a substantial proportion of patients with
      active R/R-AML.

PMID- 29468632
TI  - Autonomic function test in progressive lacunar infarction.
AB  - OBJECTIVE: Neurological progression is a major problem in managing the patients
      with acute lacunar infarction. The purpose of this was to investigate whether
      autonomic dysfunction is associated with neurological progression in patients
      with acute lacunar infarction. MATERIALS AND METHODS: The study comprised 60
      patients with acute lacunar infarction. All enrolled subjects underwent autonomic
      function tests including the 30 degrees  head-up tilt test, Valsalva test, heart
      rate response to deep breathing, and sympathetic skin response. The primary
      endpoint is the neurological progression, and the secondary endpoint is the 3
      month outcome. RESULTS: Increased initial National Institute of Health stroke
      scale (NIHSS), decreased time to admission from onset, decreased rise of heart
      rate in the 30 degrees  head-up tilt test, abnormal blood pressure response in
      the Valsalva test, and decreased rise of systolic blood pressure in stage IV of
      the Valsalva test are associated with neurological progression of acute lacunar
      infarction; an abnormal blood pressure response in the Valsalva test is
      significant in logistic regression analysis of neurological progression. Advanced
      age, increased initial NIHSS and modified Rankin scale, decreased
      expiration/inspiration ratio of heart rate to deep breathing, decreased rise of
      systolic blood pressure in stage IV of the Valsalva test, and neurological
      progression were associated with an unfavorable 3-month outcome; neurological
      progression was significant in logistic regression analysis of 3-month outcome.
      CONCLUSIONS: An abnormal blood pressure change in the Valsalva test is associated
      with neurological progression in patients with acute lacunar infarction, and
      neurological progression can induce an unfavorable 3-month outcome.

PMID- 29468633
TI  - Prostaglandin gel versus oxytocin - prelabour rupture of membranes at term - A
      randomised controlled trial.
AB  - BACKGROUND: Pre-labour rupture of membranes (PROM) at term is a common event with
      early induction of labour reducing infectious morbidity without increasing the
      caesarean rate. Syntocinon is commonly used for induction but prostaglandins are
      also routinely used. Large studies have shown no difference in the maternal and
      neonatal outcomes with either method. AIM: To assess the safety and efficacy of
      vaginal prostaglandin (PG) compared to syntocinon for induction of labour in term
      PROM. METHOD: This was a single-centre randomised controlled trial at Ipswich
      Hospital of women presenting at >=37 weeks gestation with PROM. Women were
      randomised and managed in labour as per local guidelines. Analysis was by
      intention to treat. RESULTS: One hundred and eighty-four women were recruited, 90
      in the PG group and 94 in the oxytocin group. Women in both arms were of similar
      demographics and 53% of women in the PG group did not require any oxytocin. There
      was a statistically significant lower incidence of fetal heart rate abnormality
      in the PG group, 4.4% versus 12.8%. There was no difference in epidural use,
      caesarean section, maternal infection, admission to special care nursery or
      neonatal sepsis. Time to onset of labour was significantly longer in the PG
      group, 25.7 h versus 19.7 h but with no difference in the length of first stage.
      Maternal satisfaction was high in both groups with no significant difference in
      breastfeeding rates. CONCLUSION: Induction of labour with oxytocin or vaginal
      prostaglandins are safe and efficacious options for women in the context of PROM
      at term.

PMID- 29468634
TI  - Cognitive decline in the middle-aged after surgery and anaesthesia: results from
      the Wisconsin Registry for Alzheimer's Prevention cohort.
AB  - Surgery and anaesthesia might affect cognition in middle-aged people without
      existing cognitive dysfunction. We measured memory and executive function in 964
      participants, mean age 54 years, and again four years later, by when 312
      participants had had surgery and 652 participants had not. Surgery between tests
      was associated with a decline in immediate memory by one point (out of a maximum
      of 30), p = 0.013: memory became abnormal in 77 out of 670 participants with
      initially normal memory, 21 out of 114 (18%) of whom had had surgery compared
      with 56 out of 556 (10%) of those who had not, p = 0.02. The number of operations
      was associated with a reduction in immediate memory on retesting, beta
      coefficient (SE) 0.08 (0.03), p = 0.012. Working memory decline was also
      associated with longer cumulative operations, beta coefficient (SE) -0.01 (0.00),
      p = 0.028. A reduction in cognitive speed and flexibility was associated with
      worse ASA physical status, beta coefficient (SE) 0.55 (0.22) and 0.37 (0.17) for
      ASA 1 and 2 vs. 3, p = 0.035. However, a decline in working memory was associated
      with better ASA physical status, beta coefficient (SE) -0.48 (0.21) for ASA 1 vs.
      3, p = 0.01.

PMID- 29468635
TI  - Strategies to improve recruitment to randomised trials.
AB  - BACKGROUND: Recruiting participants to trials can be extremely difficult.
      Identifying strategies that improve trial recruitment would benefit both
      trialists and health research. OBJECTIVES: To quantify the effects of strategies
      for improving recruitment of participants to randomised trials. A secondary
      objective is to assess the evidence for the effect of the research setting (e.g.
      primary care versus secondary care) on recruitment. SEARCH METHODS: We searched
      the Cochrane Methodology Review Group Specialised Register (CMR) in the Cochrane
      Library (July 2012, searched 11 February 2015); MEDLINE and MEDLINE In Process
      (OVID) (1946 to 10 February 2015); Embase (OVID) (1996 to 2015 Week 06); Science
      Citation Index & Social Science Citation Index (ISI) (2009 to 11 February 2015)
      and ERIC (EBSCO) (2009 to 11 February 2015). SELECTION CRITERIA: Randomised and
      quasi-randomised trials of methods to increase recruitment to randomised trials.
      This includes non-healthcare studies and studies recruiting to hypothetical
      trials. We excluded studies aiming to increase response rates to questionnaires
      or trial retention and those evaluating incentives and disincentives for
      clinicians to recruit participants. DATA COLLECTION AND ANALYSIS: We extracted
      data on: the method evaluated; country in which the study was carried out; nature
      of the population; nature of the study setting; nature of the study to be
      recruited into; randomisation or quasi-randomisation method; and numbers and
      proportions in each intervention group. We used a risk difference to estimate the
      absolute improvement and the 95% confidence interval (CI) to describe the effect
      in individual trials. We assessed heterogeneity between trial results. We used
      GRADE to judge the certainty we had in the evidence coming from each comparison.
      MAIN RESULTS: We identified 68 eligible trials (24 new to this update) with more
      than 74,000 participants. There were 63 studies involving interventions aimed
      directly at trial participants, while five evaluated interventions aimed at
      people recruiting participants. All studies were in health care.We found 72
      comparisons, but just three are supported by high-certainty evidence according to
      GRADE.1. Open trials rather than blinded, placebo trials. The absolute
      improvement was 10% (95% CI 7% to 13%).2. Telephone reminders to people who do
      not respond to a postal invitation. The absolute improvement was 6% (95% CI 3% to
      9%). This result applies to trials that have low underlying recruitment. We are
      less certain for trials that start out with moderately good recruitment (i.e.
      over 10%).3. Using a particular, bespoke, user-testing approach to develop
      participant information leaflets. This method involved spending a lot of time
      working with the target population for recruitment to decide on the content,
      format and appearance of the participant information leaflet. This made little or
      no difference to recruitment: absolute improvement was 1% (95% CI -1% to 3%).We
      had moderate-certainty evidence for eight other comparisons; our confidence was
      reduced for most of these because the results came from a single study. Three of
      the methods were changes to trial management, three were changes to how potential
      participants received information, one was aimed at recruiters, and the last was
      a test of financial incentives. All of these comparisons would benefit from other
      researchers replicating the evaluation. There were no evaluations in paediatric
      trials.We had much less confidence in the other 61 comparisons because the
      studies had design flaws, were single studies, had very uncertain results or were
      hypothetical (mock) trials rather than real ones. AUTHORS' CONCLUSIONS: The
      literature on interventions to improve recruitment to trials has plenty of
      variety but little depth. Only 3 of 72 comparisons are supported by high
      certainty evidence according to GRADE: having an open trial and using telephone
      reminders to non-responders to postal interventions both increase recruitment; a
      specialised way of developing participant information leaflets had little or no
      effect. The methodology research community should improve the evidence base by
      replicating evaluations of existing strategies, rather than developing and
      testing new ones.

PMID- 29468636
TI  - Oxidation catalysis by iron and manganese porphyrins within enzyme-like cages.
AB  - Inspired by natural heme-proteins, scientists have attempted for decades to
      design efficient and selective metalloporphyrin-based oxidation catalysts.
      Starting from the pioneering work on small molecule mimics in the late 1970s, we
      have assisted to a tremendous progress in designing cages of different nature and
      complexity, able to accommodate metalloporphyrins. With the intent of tuning and
      controlling their reactivity, more and more sophisticated and diverse
      environments are continuously exploited. In this review, we will survey the
      current state of art in oxidation catalysis using iron- and manganese-porphyrins
      housed within designed or engineered protein cages. We will also examine the
      innovative metal-organic framework (MOF) systems, exploited to achieving an
      enzyme-like environment around the metalloporphyrin cofactor.

PMID- 29468637
TI  - Idelalisib-rituximab induces durable remissions in TP53 disrupted B-PLL but
      results in significant toxicity: updated results of the UK-wide compassionate use
      programme.

PMID- 29468638
TI  - Accuracy of point-of-care HbA1c testing in pregnant women.
AB  - BACKGROUND: In New Zealand, it is recommended that all pregnant women have a
      haemoglobin A1c (HbA1c) test performed with their booking antenatal bloods to
      identify previously unrecognised diabetes. However, screening rates in some
      groups are low. Use of a point-of-care device may improve compliance with
      screening. AIM: To assess the accuracy of the COBAS b101 point-of-care system
      referenced against a laboratory method, for measurement of HbA1c levels in
      pregnant women. MATERIALS AND METHODS: Convenience sample of 40 obese pregnant
      women enrolled in a clinical trial. HbA1c was assayed in paired capillary and
      venous whole blood samples using the COBAS b101 point-of-care system and Primus
      Ultra2 high performance liquid chromatography laboratory analyser, respectively.
      The accuracy of the point-of-care system was assessed by Bland-Altman analysis.
      RESULTS: The mean (SD) laboratory HbA1c was 35.9 (2.0) mmol/mol. The COBAS b101
      point-of-care system, compared with the laboratory reference method, had a small
      negative bias for HbA1c (-1.0 mmol/mol, 95% CI -2.0 to -0.03, P = 0.03) and
      relatively wide 95% limits of agreement (-7.2 to 5.1 mmol/mol). CONCLUSION: In
      conclusion, we found that in pregnancy, the COBAS b101 point-of-care system has a
      small negative bias and modest point accuracy for HbA1c. When used to screen for
      previously unrecognised diabetes in pregnancy, appropriate COBAS b101 HbA1c point
      of-care HbA1c thresholds for a negative and positive result are 7 mmol/mol below
      and 5 mmol/mol above the clinical threshold, respectively. Values between these
      limits should be confirmed by laboratory testing.

PMID- 29468639
TI  - Factor XIa-triggered thrombin generation in severe haemophilia A.

PMID- 29468640
TI  - Prevalence and Preventability of Drug-Related Hospital Readmissions: A Systematic
      Review.
AB  - OBJECTIVES: To summarize the evidence on the prevalence and preventability of
      drug-related hospital readmissions. DESIGN: A systematic review was performed of
      studies that examined drug-related hospital readmissions. PubMed, EMBASE, and the
      Cochrane Library were searched from inception through August 2016. Reference
      lists and a citation analysis on Web of Science and Scopus were also consulted.
      Two reviewers extracted study data with dual assessment of risk of bias.
      Prevalence and preventability of readmission due to drugs were calculated. Data
      were qualitatively summarized according to outcome. RESULTS: Nineteen studies met
      the eligibility criteria. Nine measured readmissions due to drug-related
      problems, seven due to adverse drug reactions, two due to adverse drug events,
      and one due to drug-drug interactions. Rates of readmissions due to drugs varied
      from 3% to 64% (median 21%, interquartile range (IQR) 14-23%). Readmissions were
      deemed preventable in 5% to 87% of cases (median 69%, IQR 19-84%). Evidence
      regarding the risk factors for drug-related readmissions and drugs causing these
      readmissions was inconsistent. CONCLUSION: Although studies show high variability
      in prevalence and preventability of drug-related hospital readmissions,
      readmissions due to drugs seem to occur often, especially in older adults.
      Further research is needed to specify the causes of preventable readmissions and
      implement effective interventions to reduce medication-related hospital
      admissions.

PMID- 29468641
TI  - Cord gas parameters in infants born to women with sickle cell disease: a
      retrospective matched cohort study.

PMID- 29468642
TI  - Sensory distribution of the lateral femoral cutaneous nerve block - a randomised,
      blinded trial.
AB  - BACKGROUND: The lateral femoral cutaneous nerve (LFCN) block may be used for post
      operative pain management in patients undergoing total hip arthroplasty. The aim
      of this trial was to investigate the sensory coverage of the posterior and the
      lateral incision lines and the involvement of the femoral nerve after an LFCN
      block. METHODS: The study was a randomised, blinded trial in 20 healthy
      volunteers. All subjects received a bilateral LFCN block randomised to 8 ml
      ropivacaine on the right side and 8 ml isotonic saline on the left side, or vice
      versa. An orthopaedic surgeon depicted the incision lines (invisible to the
      investigators) prior to block performance. The distribution of the blocked area
      and the coverage of the incision lines were assessed with temperature
      discrimination and pinprick test before unblinding the incision lines. Pain
      during tonic heat stimulation and involvement of the femoral nerve by measuring
      quadriceps strength were assessed. RESULTS: The mean difference in block coverage
      of the posterior (primary outcome) and the lateral incision lines tested with
      temperature discrimination were 5.8% (95% CI: -2.2 to 14.0%, P = 0.146) and 18.9%
      (95% CI: 6.5-31.4%, P = 0.005), respectively, comparing the active with the
      placebo side. A varying anatomic distribution area was observed. No clinically
      significant differences for experimental pain and quadriceps muscle strength were
      found. The block failure rate was 15%. CONCLUSION: An LFCN block consisting of 8
      ml 0.75% ropivacaine had limited coverage of the posterior and lateral incision
      lines.

PMID- 29468644
TI  - Multinucleated giant myeloma cells after failure of daratumumab therapy.

PMID- 29468643
TI  - Development and validation of Spasticity Index-Amyotrophic Lateral Sclerosis.
AB  - OBJECTIVES: Spasticity is a common and disabling feature of amyotrophic lateral
      sclerosis (ALS). There are currently no validated ALS-specific measures of
      spasticity. The aim of this study was to develop and use a self-report outcome
      measure for spasticity in ALS. METHODS: Following semi-structured interviews with
      11 ALS patients, a draft scale was administered across ALS clinics in the UK.
      Internal validity of the scale was examined using the Rasch model. The numerical
      rating scale (NRS) for spasticity and Leeds Spasticity scale (LSS) were co
      administered. The final scale was used in a path model of spasticity and quality
      of life. RESULTS: A total of 465 patients (mean age 64.7 years (SD 10), 59% male)
      with ALS participated. Spasticity was reported by 80% of subjects. A pool of 71
      items representing main themes of physical symptoms, negative impact and
      modifying factors was subject to an iterative process of item reduction by Rasch
      analysis resulting in a 20-item scale-the Spasticity Index for ALS (SI-ALS)-which
      was unidimensional and free from differential item functioning. Moderate
      correlations were found with LSS and NRS-spasticity. Incorporating the latent
      estimate of spasticity into a path model, greater spasticity reduced quality of
      life and motor function; higher motor function was associated with better quality
      of life. CONCLUSIONS: The SI-ALS is a disease-specific self-report scale, which
      provides a robust interval-level measure of spasticity in ALS. Spasticity has a
      substantial impact on quality of life in ALS.

PMID- 29468645
TI  - Humoral immune failure defined by immunoglobulin class and immunoglobulin G
      subclass deficiency is associated with shorter treatment-free and overall
      survival in Chronic Lymphocytic Leukaemia.
AB  - Immune dysfunction attributed to hypogammaglobulinaemia is common in chronic
      lymphocytic leukaemia (CLL) and infection is a major contributor to morbidity and
      mortality. A higher incidence of multiple immunoglobulin and immunoglobulin G
      (IgG) subclass deficiency was associated with more advanced disease (P < 0.001
      and P < 0.001, respectively) in a cohort of 147 CLL patients. Multiple
      immunoglobulin and IgG subclass deficiency were significantly associated with
      shorter treatment-free survival (TFS) (P < 0.001 and P = 0.006, respectively).
      The association between disease stage and immune dysfunction demonstrated by
      these data suggest aspects of immune deficiency correlate with disease severity
      and may be associated with shorter TFS in CLL.

PMID- 29468646
TI  - Early morphological response is significantly associated with, but does not
      accurately predict, relapse in teenagers and young adults aged 10-24 years with
      acute lymphoblastic leukaemia (ALL): results from UKALL2003.

PMID- 29468647
TI  - Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin
      lymphoma: a report from the EBMT Lymphoma Working Party.
AB  - Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate. Preliminary
      data suggest that BV might improve outcomes after allogeneic stem cell
      transplantation (SCT) for Hodgkin lymphoma (HL) when used as pre-transplant
      salvage therapy. Between 2010 and 2014, 428 adult patients underwent an
      allogeneic SCT for classical HL at participating centres of the European Society
      for Blood and Marrow Transplantation. We compared the outcomes of 210 patients
      who received BV prior to allogeneic SCT with that of 218 patients who did not
      receive BV. The median follow-up for survivors was 41 months. Patients in the BV
      group were more heavily pre-treated (median pre-allograft treatment lines: 4 vs.
      3). The two groups were comparable in terms of disease status, performance
      status, comorbidities, prior autologous SCT, type of donor, conditioning and in
      vivo T cell depletion. In multivariate analysis, pre-allograft BV had no impact
      on acute graft-versus-host disease (GVHD), non-relapse mortality, cumulative
      incidence of relapse, progression-free survival or overall survival (OS), but
      significantly reduced the risk of chronic GVHD (hazard ratio = 0.64; 95%
      confidence interval = 0.45-0.92; P < 0.02). Older age, poor performance status,
      use of pre-transplant radiotherapy and active disease at SCT adversely affected
      OS. Patients allografted for HL after prior exposure to BV do not have a superior
      outcome after allogeneic SCT except for a lower risk of chronic GVHD. However, BV
      may improve the outlook of allogeneic SCT by helping otherwise refractory
      patients to achieve a more favourable disease status, facilitating allotransplant
      success.

PMID- 29468648
TI  - Anti-thymocyte globulin for graft-versus-host disease prophylaxis in patients
      with intermediate- or high-risk acute myeloid leukaemia undergoing reduced
      intensity conditioning allogeneic stem cell transplantation in first complete
      remission - a survey on behalf of the Acute Leukaemia Working Party of the
      European Society for Blood and Marrow Transplantation.

PMID- 29468649
TI  - Is anticoagulating haemodialysis patients with non-valvular atrial fibrillation
      too risky?
AB  - There is an increasing understanding of the risks from atrial fibrillation (AF)
      in the current era. In patients with end-stage renal disease (ESRD) on dialysis,
      the prevalence of AF is significantly higher compared to the general population
      and those with earlier stages of CKD. Although anticoagulation of these patients
      may seem appropriate, there is a lack of conclusive evidence that it provides the
      same protection from thromboembolic complications as it does in patients not on
      dialysis. In addition, the increased risk of bleeding in patients requiring
      dialysis makes the use of anticoagulants less favourable. This article aims to
      discuss the problem of AF in dialysis patients, summarise the current evidence
      around the use of oral anticoagulants for AF in ESRD and provide some practical
      suggestions on management of AF in the haemodialysis population.

PMID- 29468650
TI  - Hepatitis E virus - key points for the clinical haematologist.
AB  - In recent years there has been a paradigm shift in our understanding of the
      epidemiology and clinical features of hepatitis E virus (HEV) infection. Once
      classically described as an acute hepatitis associated with waterborne outbreaks
      in areas of poor sanitation, HEV is now recognised to be endemic in Europe and is
      probably zoonotic in origin. Evidence for transfusion-transmitted HEV has
      prompted the introduction of blood donor screening in a number of countries, but
      the risk to the haematology patient from food sources remains. The aim of this
      review therefore, is to equip the clinical haematologist with the knowledge
      required to diagnose HEV infection and to aid decision-making in patient
      management. The article also provides information on addressing patient concerns
      about their risk of acquiring hepatitis E and how this risk can be mitigated.

PMID- 29468651
TI  - Dose-intense chemoimmunotherapy plus radioimmunotherapy in high-risk diffuse
      large B-cell lymphoma and mantle cell lymphoma: a phase II study.

PMID- 29468652
TI  - Response and survival for primary therapy combination regimens and maintenance
      rituximab in Waldenstrom macroglobulinaemia.
AB  - Waldenstrom macroglobulinaemia (WM) is a rare and incurable lymphoma. Comparative
      studies evaluating the efficacy of primary therapy in symptomatic WM patients
      have not been performed. In this study, we compared response and survival
      outcomes in WM patients who received primary therapy with cyclophosphamide
      dexamethasone-rituximab (CDR), bortezomib-dexamethasone-rituximab (BDR) and
      bendamustine-rituximab (Benda-R), as well as maintenance rituximab following
      primary therapy. Analyses were adjusted for relevant clinical factors associated
      with response and survival. Maintenance rituximab was analysed as a time-varying
      covariate. Our study included 182 patients, of which 57 (31%) received Benda-R,
      87 (48%) BDR and 38 (21%) CDR; 116 (64%) received maintenance rituximab. The
      median time to best response was shorter for Benda-R and BDR than CDR (18, 20 and
      30 months, respectively). Benda-R and BDR were associated with better median
      progression-free survival (PFS) than CDR (5.5, 5.8 and 4.8 years, respectively),
      and better 10-year overall survival rates (OS; 95%, 96% and 81%, respectively).
      Maintenance rituximab was associated with higher rates of major response (97% vs.
      68%), and better median PFS (6.8 years vs. 2.8 years) and 10-year OS rate (84%
      vs. 66%) when compared to not receiving maintenance. Benda-R, BDR and maintenance
      rituximab associate with higher response rates and longer survival in WM patients
      than CDR and no maintenance, respectively.

PMID- 29468653
TI  - Ferritin as a functional biomarker of iron status in children and young adults.

PMID- 29468654
TI  - Experimental evolution across different thermal regimes yields genetic divergence
      in recombination fraction but no divergence in temperature associated plastic
      recombination.
AB  - Phenotypic plasticity is pervasive in nature. One mechanism underlying the
      evolution and maintenance of such plasticity is environmental heterogeneity.
      Indeed, theory indicates that both spatial and temporal variation in the
      environment should favor the evolution of phenotypic plasticity under a variety
      of conditions. Cyclical environmental conditions have also been shown to yield
      evolved increases in recombination frequency. Here, we use a panel of replicated
      experimental evolution populations of D. melanogaster to test whether variable
      environments favor enhanced plasticity in recombination rate and/or increased
      recombination rate in response to temperature. In contrast to expectation, we
      find no evidence for either enhanced plasticity in recombination or increased
      rates of recombination in the variable environment lines. Our data confirm a role
      of temperature in mediating recombination fraction in D. melanogaster, and
      indicate that recombination is genetically and plastically depressed under lower
      temperatures. Our data further suggest that the genetic architectures underlying
      plastic recombination and population-level variation in recombination rate are
      likely to be distinct.

PMID- 29468656
TI  - Cough and ACE Inhibitors: The Truth Beyond Placebo.
AB  - Angiotensin converting enzyme (ACE) inhibitors are extensively used for the
      prevention and treatment of cardiovascular diseases with a wide range of clinical
      recommendations. The use of ACE inhibitors can cause the onset of a dry cough,
      whose prevalence has probably been overestimated because of the lack of adequate
      control. A correct interpretation of available data requires a careful evaluation
      of placebo-controlled studies to definitely assess the rate of the most frequent
      adverse event of ACE inhibition.

PMID- 29468657
TI  - Comparative analysis of the outcomes of elective abdominal aortic aneurysm repair
      in England and Sweden.
AB  - BACKGROUND: There is substantial international variation in mortality after
      abdominal aortic aneurysm (AAA) repair; many non-operative factors influence risk
      adjusted outcomes. This study compared 90-day and 5-year mortality for patients
      undergoing elective AAA repair in England and Sweden. METHODS: Patients were
      identified from English Hospital Episode Statistics and the Swedish Vascular
      Registry between 2003 and 2012. Ninety-day mortality and 5-year survival were
      compared after adjustment for age and sex. Separate within-country analyses were
      performed to examine the impact of co-morbidity, hospital teaching status and
      hospital annual caseload. RESULTS: The study included 36 249 patients who had AAA
      treatment in England, with a median age of 74 (i.q.r. 69-79) years, of whom 87.2
      per cent were men. There were 7806 patients treated for AAA in Sweden, with a
      median of age 73 (68-78) years, of whom 82.9 per cent were men. Ninety-day
      mortality rates were poorer in England than in Sweden (5.0 versus 3.9 per cent
      respectively; P < 0.001), but were not significantly different after 2007. Five
      year survival was poorer in England (70.5 versus 72.8 per cent; P < 0.001). Use
      of EVAR was initially lower in England, but surpassed that in Sweden after 2010.
      In both countries, poor outcome was associated with increased age. In England,
      institutions with higher operative annual volume had lower mortality rates.
      CONCLUSION: Mortality for elective AAA repair was initially poorer in England
      than Sweden, but improved over time alongside greater uptake of EVAR, and now
      there is no difference. Centres performing a greater proportion of EVAR
      procedures achieved better results in England.

PMID- 29468655
TI  - GPCRs in pulmonary arterial hypertension: tipping the balance.
AB  - Pulmonary arterial hypertension (PAH) is a progressive, fatal disease
      characterised by increased pulmonary vascular resistance and excessive
      proliferation of pulmonary artery smooth muscle cells (PASMC). GPCRs, which are
      attractive pharmacological targets, are important regulators of pulmonary
      vascular tone and PASMC phenotype. PAH is associated with the altered expression
      and function of a number of GPCRs in the pulmonary circulation, which leads to
      the vasoconstriction and proliferation of PASMC and thereby contributes to the
      imbalance of pulmonary vascular tone associated with PAH; drugs targeting GPCRs
      are currently used clinically to treat PAH and extensive preclinical work
      supports the utility of a number of additional GPCRs. Here we review how GPCR
      expression and function changes with PAH and discuss why GPCRs continue to be
      relevant drug targets for the disease.

PMID- 29468658
TI  - Dermatology hospitalists: a multicenter survey study characterizing the
      infrastructure of consultative dermatology in select American hospitals.
AB  - BACKGROUND: Although considered an outpatient specialty, dermatology plays an
      important role in inpatient medicine. We characterized the activity and structure
      of dermatology consultation services in select U.S. hospitals. METHODS: In this
      cross sectional study, a 31-question survey was distributed in person to 32 board
      certified dermatologists at the 2017 Society of Dermatology Hospitalists meeting.
      RESULTS: Thirty participants completed the survey (yield 93.8%). Most dermatology
      hospitalists spend 41-52 weeks on service (50%), with 37% spending between 11 and
      30 weeks. Coverage was organized by continuous weeks (68%) or months (21%). While
      on service, hospitalists staffed an average of 4 outpatient clinics per week.
      Consultative teams also included internal medicine residents (43%), medical
      students (47%), pediatric residents (10%), and fellows from other specialties
      (27%). Consultation services saw approximately 3.7 new inpatients and 4.2 follow
      up inpatients per day, with daily rounds lasting approximately 2.6 hours.
      CONCLUSIONS: The results suggest that hospital dermatologists in the U.S.
      consider inpatient care their niche and devote a majority of their time staffing
      consults over clinic. The diverse composition of inpatient teams and the number
      of academic duties held by these physicians suggests they play an important role
      in medical education.

PMID- 29468659
TI  - Response to "Influence of Diabetes on Antiplatelet Drug Efficacy".

PMID- 29468660
TI  - Spatiotemporal homogeneity and distinctness of the T-cell receptor beta-chain
      repertoires in Epstein-Barr virus-associated primary and metastatic
      nasopharyngeal carcinomas.
AB  - Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated
      lymphoepithelioma. The aim of this study was to characterize the homogeneity and
      distinctness of the T-cell repertoires within and between primary and metastatic
      NPCs. We used ultra-deep sequencing of the hypervariably rearranged antigen
      binding CDR3 regions of T-cell receptor beta (TCRbeta ) to comprehensively
      profile the T-cell repertoires in NPC patients receiving definitive
      chemoradiotherapy with long-term follow-up. We observed not only various
      spatially heterogeneous patient-specific TCRbeta clone compositions that changed
      with time but also several commonly enriched TCRbeta subclones that were
      constantly shared between primary NPCs in the head and neck regions, locally
      recurrent tumors after treatment and later-developed distant metastatic tumors in
      the liver, lung and bone. Comparison of the overlap frequency of the T-cell
      clonality between TCRbeta repertoires enabled us to calculate the pairwise
      genetic distance between primary NPCs of different patients and different sites
      of metastatic or recurrent NPCs. The constructed NPC phylogeny clearly
      differentiated the low-risk patients without relapse from the high-risk patients
      with distant metastasis after chemoradiotherapy. In contrast to the rather low
      frequency of nonsilent somatic mutations in NPC cells, the degrees of similarity
      and divergence of NPC-infiltrating lymphocyte TCRbeta repertoires among different
      patients showed prognostication. Moreover, the persistent presence of commonly
      NPC-shared in-frame TCRbeta CDR3 gene sequences spatiotemporally identified in
      the NPC-infiltrating lymphocytes within varied EBV-positive NPCs and their
      metastases suggest the existence of frequently shared epitopes of neoantigens
      virally or nonvirally displayed on cancer cells, thereby providing opportunities
      for the development of precisely tumor-targeted immunotherapy for distant
      metastasis.

PMID- 29468661
TI  - Molecular and clinical studies in 8 patients with Temple syndrome.
AB  - Temple syndrome (TS14, #616222) is a rare imprinting disorder characterised by
      phenotypic features including pre- and postnatal growth retardation, muscular
      hypotonia and feeding difficulties in infancy, early puberty and short stature
      with small hands and feet and often truncal obesity. It is caused by maternal
      uniparental disomies, paternal deletions and primary imprinting defects that
      affect the chromosomal region 14q32 and lead to a disturbed expression of
      imprinted genes in this region. Here, we present detailed clinical data of 8
      patients with Temple syndrome, 4 with an imprinting defect, 2 with an imprinting
      defect in a mosaic state as well as 1 complete and 1 segmental maternal
      uniparental disomy of chromosome 14.

PMID- 29468662
TI  - Predictive validity of spontaneous early infant movement for later cerebral
      palsy: a systematic review.
AB  - AIM: To systematically review the predictive validity of spontaneous early infant
      movements for later cerebral palsy (CP). METHOD: Cohort studies with published
      data to calculate predictive validity of early spontaneous movements for later CP
      were searched in four electronic databases: CINAHL, Embase, MEDLINE, and
      PsycINFO. RESULTS: Forty-seven studies met inclusion criteria. The Prechtl
      General Movements Assessment (GMA) during the fidgety period (10-20wks corrected
      age) had the strongest sensitivity: 97 per cent (95% confidence interval [CI] 93
      99) and specificity: 89% (95% CI 83-93). The sensitivity and specificity of the
      Prechtl GMA during the writhing period (birth-6wks) was 93% (95% CI 86-96) and
      59% (95% CI 45-71) respectively. Cramped-synchronized movements in the writhing
      period according to Prechtl had the best specificity (sensitivity: 70% [95% CI 54
      82]; specificity: 97% [95% CI 74-100]). Hadders-Algra's method of assessing
      general movements had a pooled sensitivity and specificity of 89% (95% CI 66-97)
      and 81% (95% CI 64-91) respectively. Presence of asymmetric postures and movement
      quality/quantity were reported under the Hammersmith Infant Neurological
      Examination, Hammersmith Neonatal Neurological Examination, and Movement
      Assessment of Infants but had weak associations with later CP. INTERPRETATION:
      Fidgety movements assessed by the Prechtl GMA have the strongest predictive
      validity for later CP, but cannot be considered in isolation because of the
      presence of false positive results. WHAT THIS PAPER ADDS: Fidgety general
      movements (Prechtl) are most predictive for later cerebral palsy compared with
      other spontaneous movements. False positive results are high among all
      spontaneous movement assessments.

PMID- 29468663
TI  - Radiological imaging and bone marrow biopsy in staging of cutaneous B-cell
      lymphoma.

PMID- 29468664
TI  - Adverse mental health outcomes in a population-based cohort of survivors of
      childhood cancer.
AB  - BACKGROUND: The elevated risk for physical late effects in childhood cancer
      survivors (CCS) is well documented, but their risk for mental health problems is
      less well described. METHODS: The authors assembled a cohort of all 5-year CCS
      who were diagnosed before age 18 years and treated in an Ontario pediatric cancer
      center between 1987 and 2008. Patients were matched to population controls and
      linked to health administration databases. The authors calculated rates of mental
      health care visits (family physician, psychiatrist, emergency department,
      hospitalization) and the risk for a severe mental health event (emergency
      department, hospitalization, suicide). Outcomes were compared using recurrent
      event and survival analyses. RESULTS: Compared with 20,269 controls, 4117 CCS had
      a higher rate of mental health visits (adjusted relative rate [RR], 1.34; 95%
      confidence interval [CI], 1.12-1.52). Higher rates were associated with female
      gender (RR, 1.39; CI, 1.10-1.75; P = .006) and being diagnosed at ages 15 to 17.9
      years (compared with ages 0-4 years: RR, 1.81; 95% CI, 1.17-2.80; P = .008).
      Cancer type, treatment intensity, and treatments targeting the central nervous
      system were not significant predictors. Survivors were at increased risk for a
      severe event compared with controls (adjusted hazard ratio, 1.13; 95% CI, 1.00
      1.28; P = .045). CCS who were diagnosed with cancer at age 4 years or younger
      were at greatest risk: 16.3% (95% CI, 13.2%-19.8%) had experienced a severe event
      by age 28 years. CONCLUSIONS: CCS experienced higher rates of mental health
      visits and a greater risk for a severe event than the general population.
      Survivors of adolescent cancer have a higher rate of mental health visits
      overall, whereas survivors of cancer before age 4 years have a markedly elevated
      risk of severe events. Cancer 2018;124:2045-57. (c) 2018 American Cancer Society.

PMID- 29468665
TI  - Promoting optimal bimanual performance in cerebral palsy.

PMID- 29468666
TI  - Eicosanoids, prostacyclin and cyclooxygenase in the cardiovascular system.
AB  - Eicosanoids represent a diverse family of lipid mediators with fundamental roles
      in physiology and disease. Within the eicosanoid superfamily are prostanoids,
      which are specifically derived from arachidonic acid by the enzyme cyclooxygenase
      (COX). COX has two isoforms; COX-1 and COX-2. COX-2 is the therapeutic target for
      the nonsteroidal anti-inflammatory drug (NSAID) class of pain medications. Of the
      prostanoids, prostacyclin, first discovered by Sir John Vane in 1976, remains
      amongst the best studied and retains an impressive pedigree as one of the
      fundamental cardiovascular protective pathways. Since this time, we have learnt
      much about how eicosanoids, COX enzymes and prostacyclin function in the
      cardiovascular system, knowledge that has allowed us, for example, to harness the
      power of prostacyclin as therapy to treat pulmonary arterial hypertension and
      peripheral vascular disease. However, there remain many unanswered questions in
      our basic understanding of the pathways, and how they can be used to improve
      human health. Perhaps, the most important and controversial outstanding question
      in the field remains; 'how do NSAIDs produce their much publicized cardiovascular
      side-effects?' This review summarizes the history, biology and cardiovascular
      function of key eicosanoids with particular focus on prostacyclin and other COX
      products and discusses how our knowledge of these pathways can applied in future
      drug discovery and be used to explain the cardiovascular side-effects of NSAIDs.

PMID- 29468667
TI  - Teachers' knowledge concerning dental trauma and its management in primary
      schools in Riyadh, Saudi Arabia.
AB  - OBJECTIVES: The main aim of this cross-sectional study was to assess knowledge
      concerning traumatic dental injuries and their management among primary
      schoolteachers in Riyadh, Saudi Arabia. The secondary objective was to evaluate
      the effect of gender, nationality, marital status, school type, geographical
      area, age group, level of education and years of experience on teachers'
      knowledge. METHODOLOGY: Data were collected, through a self-administered
      questionnaire, from both male and female teachers employed in public and private
      primary schools in the five geographical areas of Riyadh City. The total sample
      size was 1,520 teachers. Data were entered into the Statistical Package for the
      Social Sciences. Frequencies and percentages were calculated. An independent t
      test and a one-way analysis of variance (ANOVA) were used to calculate
      significance. RESULTS: The total score for the questions assessing knowledge was
      calculated out of 9, and the highest score was 7 with an average score of 2.85.
      Over half of the sampled participants stated that they did not know how to manage
      soft-tissue injuries. Regarding the management of fractured teeth, 38.8% believed
      that the fractured part is useless; and for the management of an avulsed
      permanent tooth, only 6.2% of the respondents selected the correct answer. For
      the question regarding suitable storage medium of an avulsed tooth, only 19.7%
      chose milk and 3.2% chose the injured person's saliva. Teachers between 41 and 50
      years of age and those with longer years of experience had the highest level of
      knowledge. Teachers in the north area of Riyadh had a higher level of knowledge
      than teachers in other areas. CONCLUSION: There was a lack of knowledge among
      primary schoolteachers in Riyadh concerning traumatic dental injuries and their
      management. Statistically significant differences were found among geographical
      areas, age groups and years of experience; no statistically significant
      differences were found regarding gender, nationality, marital status, level of
      education and school type (public/private).

PMID- 29468668
TI  - Myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies are highly
      specific in children with acquired demyelinating syndromes.
AB  - AIM: Our objectives were to evaluate the utility of measuring myelin
      oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies (Ab) in
      clinical practice and describe their associated neurological phenotypes in
      children. METHOD: Between 2012 and 2017, 371 children with suspected acquired
      demyelinating syndromes (ADS) seen in three tertiary centres were tested for MOG
      Ab and AQP4-Ab. Medical notes were retrospectively reviewed, and clinical and
      demographic data compiled. Clinical phenotyping was performed blinded to the
      antibody results. RESULTS: After review, 237 of the 371 were diagnosed with ADS.
      Of these, 76 out of 237 (32.1%) were MOG-Ab positive and 14 out of 237 (5.9%)
      were AQP4-Ab positive. None were positive for both autoantibodies. All 134
      patients with non-ADS were negative for MOG-Ab. MOG-Ab were identified in 45 out
      of 70 (64.3%) patients presenting with acute disseminated encephalomyelitis
      (ADEM) and in 24 out of 25 patients with relapsing ADEM. Thirty-six out of 75
      (48%) MOG-Ab positive patients relapsed. Of the 33 children with neuromyelitis
      optic spectrum disorder, 14 were AQP4-Ab positive, 13 were MOG-Ab positive, and 6
      were seronegative. Of the children with longitudinal samples, 8 out of 13 AQP4-Ab
      remained positive during the disease course compared to 35 out of 43 MOG-Ab
      (13/16 monophasic and 22/27 relapsing). INTERPRETATION: Myelin oligodendrocyte
      glycoprotein antibodies were identified in a third of children with ADS. Almost
      half of the MOG-Ab positive children relapsed and the majority of them remained
      antibody positive over 4-years follow-up. WHAT THIS PAPER ADDS: Myelin
      oligodendrocyte glycoprotein antibodies (MOG-Ab) are highly specific for acquired
      demyelinating syndromes (ADS). Myelin oligodendrocyte glycoprotein antibodies are
      not identified in children with peripheral demyelination or genetic
      leukodystrophies/hypomyelination. Up to 48% of MOG-Ab ADS paediatric patients
      relapse, higher than previously thought. Seroconversion to MOG-Ab negative status
      is infrequent; patients may test MOG-Ab positive at follow-up sampling even when
      asymptomatic. Myelin oligodendrocyte glycoprotein antibodies status should only
      be used in conjunction with the clinical information to guide maintenance
      therapy.

PMID- 29468670
TI  - Housing Interventions and the Chronic and Acute Risks of Family Homelessness:
      Experimental Evidence for Education.
AB  - This study considers risk associated with family homelessness for school
      functioning and experimental evidence on the effects of different housing
      interventions over time. Students in homeless families (N = 172; Mage  = 7.31; SD
      = 4.15) were randomized to housing interventions that focus on acute risks
      (community-based rapid rehousing), chronic risks (permanent subsidy), or usual
      care (UC). A matched group of low-income, housed students served as an additional
      reference for effects on attendance, school mobility, and reading and math
      achievement across 4 years. Findings partially support the chronic-risk
      hypothesis that family homelessness interferes with achievement through its
      relation to deep poverty. Children randomly assigned to UC perform as well or
      better than children assigned to housing interventions in this municipality.

PMID- 29468669
TI  - Racial/Ethnic Differential Effects of Medicaid Expansion on Health Care Access.
AB  - OBJECTIVE: To assess racial/ethnic differential impacts of the ACA's Medicaid
      expansion on low-income, nonelderly adults' access to primary care. DATA SOURCES:
      Behavioral Risk Factor Surveillance System, State Physicians Workforce Data Book,
      and Bureau of Labor Statistics, in 2013 and 2015. STUDY DESIGN: Quasi
      experimental design with difference-in-differences analyses. Outcomes included
      health insurance coverage, having personal doctor(s), being unable to see doctors
      because of cost, and receiving a flu shot. We tested racial/ethnic differential
      impacts using the "Seemingly unrelated estimation" method. Multiple imputations
      and survey weights were used. DATA COLLECTION/EXTRACTION METHODS: Low-income,
      nonelderly adults were identified based on age, household income, and family
      size. PRINCIPAL FINDINGS: Among the low-income, nonelderly adults, Medicaid
      expansion was associated with statistically significant gains in health insurance
      coverage, having personal doctors, and affordability. Hispanics got the fewest
      benefits, which significantly widened racial/ethnic disparities for the Hispanic
      group. Racial/ethnic disparity in having personal doctors narrowed for non
      Hispanic black and non-Hispanic others, although not statistically significant.
      CONCLUSION: Medicaid expansion improved access to primary care, but it had
      differential effects among racial/ethnic groups resulting in mixed effects on
      disparities. Further research is necessary to develop tailored policy tools for
      racial/ethnic groups.

PMID- 29468671
TI  - A Practical Grid-Based Alternative Method to Advective Particle Tracking.
AB  - Advective particle tracking is a conventional groundwater modeling technique that
      is widely used as a screening tool but lacks robustness as a reliable method for
      general applications. In this work, we investigate the suitability of industry
      standard, finite-difference, grid-based methods as an alternative to the
      conventional particle-tracking approach. The presented method is classified as a
      particular case of the more general forward- or backward-in-time advective
      dispersive probabilistic transport approaches. The proposed method is used as a
      powerful screening tool to accurately delineate and visualize capture zones
      around abstraction wells or outflow boundaries, the swept zones formed by
      injection wells or inflow boundaries, and the partitions associated with
      injection-pumping well doublets or inflowing-outflowing boundary pairs. Moreover,
      we show that the forward or backward travel times and residence time
      distributions are robustly simulated and visualized on the computational grid
      with little computational effort. Two examples are given to illustrate the key
      advantages of this method in groundwater applications. The first example
      considers a synthetic pump-and-treat remediation system in an irregularly layered
      aquifer. The second example involves four doublet wells operating for heat
      extraction in the Dogger geothermal reservoir in the Paris Basin, a leading
      European scale project. The presented approach is far more comprehensive as a
      screening tool than the conventional method, providing a natural intermediate
      step before processing the more general time-dependent advective-dispersive
      simulations.

PMID- 29468672
TI  - CaV 3.2 drives sustained burst-firing, which is critical for absence seizure
      propagation in reticular thalamic neurons.
AB  - OBJECTIVE: Genetic alterations have been identified in the CACNA1H gene, encoding
      the CaV 3.2 T-type calcium channel in patients with absence epilepsy, yet the
      precise mechanisms relating to seizure propagation and spike-wave-discharge (SWD)
      pacemaking remain unknown. Neurons of the thalamic reticular nucleus (TRN)
      express high levels of CaV 3.2 calcium channels, and we investigated whether a
      gain-of-function mutation in the Cacna1h gene in Genetic Absence Epilepsy Rats
      from Strasbourg (GAERS) contributes to seizure propagation and pacemaking in the
      TRN. METHODS: Pathophysiological contributions of CaV 3.2 calcium channels to
      burst firing and absence seizures were assessed in vitro using acute brain slice
      electrophysiology and quantitative real-time polymerase chain reaction (PCR) and
      in vivo using free-moving electrocorticography recordings. RESULTS: TRN neurons
      from GAERS display sustained oscillatory burst-firing that is both age- and
      frequency-dependent, occurring only in the frequencies overlapping with GAERS
      SWDs and correlating with the expression of a CaV 3.2 mutation-sensitive splice
      variant. In vivo knock-down of CaV 3.2 using direct thalamic injection of lipid
      nanoparticles containing CaV 3.2 dicer small interfering (Dsi) RNA normalized TRN
      burst-firing, and in free-moving GAERS significantly shortened seizures.
      SIGNIFICANCE: This supports a role for TRN CaV 3.2 T-type channels in propagating
      thalamocortical network seizures and setting the pacemaking frequency of SWDs.

PMID- 29468673
TI  - Chronic pain prevalence and associated factors in adolescents with and without
      physical disabilities.
AB  - AIM: Adolescents with physical disabilities may have co-occurring chronic pain,
      but the prevalence and specific associated factors are unknown. The aims of this
      study were to determine (1) the prevalence of chronic pain in adolescents with
      physical disabilities and (2) whether known correlates of chronic pain in the
      general population are also present in young people both with physical disability
      and with chronic pain relative to peers. METHOD: We conducted a secondary
      analysis of cross-sectional nationally representative data from the National
      Longitudinal Study of Adolescent to Adult Health. Multivariate linear regression
      analysis was used to identify demographic and psychosocial factors associated
      with chronic pain. RESULTS: A total of 989 (4.3%) adolescents reported physical
      disabilities. They had a significantly higher rate of pain (27.2%) compared with
      able-bodied peers (15.6%, chi2 =86.3550, p<0.001). There was no significant
      interaction between physical disability status and chronic pain in relation to
      depressive symptoms, anxiety, or insomnia. INTERPRETATION: Adolescents with
      physical disabilities experience chronic pain at a significantly higher rate than
      able-bodied peers, but the comorbidity of physical disability and chronic pain is
      not related to depression, anxiety, or insomnia. Evaluation of chronic pain and
      tailored pain interventions need to be developed for this population. WHAT THIS
      PAPER ADDS: Chronic pain and its correlates are important problems for
      adolescents with physical disabilities. These adolescents present with higher
      rates of chronic pain than other young people. Chronic pain is associated with
      increased levels of depressive symptoms, anxiety, and insomnia regardless of
      disability status.

PMID- 29468674
TI  - Mental health of long-term survivors of childhood and young adult cancer: A
      systematic review.
AB  - Childhood cancer is increasing in prevalence whilst survival rates are improving.
      The prevalence of adult survivors of childhood cancer is consequently increasing.
      Many survivors suffer long-term consequences of their cancer treatment. Whilst
      many of these are well documented, relatively little is known about the mental
      health of survivors of childhood cancer. This article aimed to describe the
      prevalence and spectrum of mental health problems found in adult survivors of
      childhood cancer using a systematic review methodology. Our review included 67
      articles, describing a number of problems, including depression, anxiety,
      behavioural problems and drug misuse. Factors increasing the likelihood of mental
      health problems included treatment with high-dose anthracyclines, cranial
      irradiation, diagnoses of sarcoma or central nervous system tumours and ongoing
      physical ill health. There were numerous limitations to the studies we found,
      including use of siblings of survivors as a control group, self-report
      methodology and lack of indications for prescriptions when prescribing data were
      used. This review has identified many mental health problems experienced by
      survivors of childhood cancer; however, the exact incidence, prevalence and risk
      factors for their development remain unclear. Further work to identify childhood
      cancer patients who are at risk of developing late mental health morbidity is
      essential.

PMID- 29468675
TI  - Market Competition and Health Outcomes in Hemodialysis.
AB  - OBJECTIVE: To examine whether market competition is associated with improved
      health outcomes in hemodialysis. DATA SOURCES: Secondary analysis of data from a
      national dialysis registry between 2001 and 2011. STUDY DESIGN: We conducted one-
      and two-part linear regression models, using each hospital service area (HSA) as
      its own control, to examine the independent associations among market
      concentration and health outcomes. DATA COLLECTION: We selected cohorts of
      patients receiving in-center hemodialysis in the United States at the start of
      each calendar year. We used information about dialysis facility ownership and the
      location where patients received dialysis to measure an index of market
      concentration-the Hirschman-Herfindahl Index (HHI)-for HSA and year, which ranges
      from near zero (perfect competition) to one (monopoly). PRINCIPAL FINDINGS: An
      average reduction in HHI by 0.2 (one standard deviation in 2011) was associated
      with 2.9 fewer hospitalizations per 100 patient-years (95 percent CI, 0.4 to
      5.4). If these findings were generalized to the entire in-center hemodialysis
      population, this would translate to 8,100 (95 percent CI 1,200 to 15,000) fewer
      hospitalizations in 2011. There was no association between change in market
      competition and mortality. CONCLUSIONS: Market competition in dialysis may lead
      to improved health outcomes.

PMID- 29468676
TI  - Relationships among gestational age and birthweight with cognitive deficits in
      children and adolescents born very preterm.

PMID- 29468677
TI  - Determination of kQmsr,Q0fmsr,fref factors for ion chambers used in the
      calibration of Leksell Gamma Knife Perfexion model using EGSnrc and PENELOPE
      Monte Carlo codes.
AB  - PURPOSE: To calculate the kQmsr,Q0fmsr,fref factors for nine common ionization
      chamber types following the small fields dosimetry formalism for the calibration
      of the Leksell Gamma Knife(r) (LGK) PerfexionTM using Monte Carlo simulation.
      This study also provides the first independent comparison of EGSnrc and PENELOPE
      for the calculation of kQmsr,Q0fmsr,fref correction factors and proposes a
      practical method to predict these factors based on chamber type, chamber
      orientation and phantom electron density. METHODS: The ionization chambers are
      modeled using the EGSnrc and PENELOPE Monte Carlo codes based on the blueprints
      provided by the manufacturers. The chambers are placed in a half-sphere water
      phantom and five spherical phantoms made of liquid water, solid water, ABS,
      polystyrene, and PMMA, respectively. Dose averaged over the air cavity of the
      chambers and a small water volume are calculated using EGSnrc and PENELOPE Monte
      Carlo codes for both conventional and machine specific reference (msr) setups.
      Using the calculated dose ratio, the kQmsr,Q0fmsr,fref factor is determined for
      all phantom materials and two possible orientations of chamber. The calculated
      kQmsr,Q0fmsr,fref factors are compared to a previous Monte Carlo study. A
      relationship between the kQmsr,Q0fmsr,fref factor and the electron density of the
      phantom material is derived to predict the kQmsr,Q0fmsr,fref factor for any
      phantom material type. Applying the calculated kQmsr,Q0fmsr,fref factors to the
      measured dose rate of a recent round robin study improves consistency of
      reference dosimetry of the Leksell Gamma Knife(r) (LGK) PerfexionTM . RESULTS:
      Agreement within uncertainty is observed between kQmsr,Q0fmsr,fref values
      determined in this study and the previous PEGASOS/PENELOPE study in a liquid
      water phantom. The difference between kQmsr,Q0fmsr,fref values in parallel and
      perpendicular detector orientations is most significant for the PTW 31010 (1.8%)
      chamber. The percentage root-mean-square (%RMS) deviation between EGSnrc and
      PENELOPE calculated kQmsr,Q0fmsr,fref values for Exradin-A1SL, A14 and A14SL
      chambers studies in this work was found to be 0.4%. The kQmsr,Q0fmsr,fref values
      increase linearly with electron density of the phantom material for all chamber
      types mainly due to the linear dependency of photon energy fluence ratios on
      electron density. The average percentage difference between the calculated and
      predicted kQmsr,Q0fmsr,fref values using two methods is found to be 0.15% and
      0.16%. Previously measured dose rates corrected with the kQmsr,Q0fmsr,fref values
      determined in this work leads to absorbed dose values consistent to within 0.8%.
      CONCLUSIONS: The calculated kQmsr,Q0fmsr,fref values in this work will enable
      users to apply the appropriate correction for their own specific phantom material
      only knowing the electron density of the phantom material.

PMID- 29468678
TI  - Image guidance doses delivered during radiotherapy: Quantification, management,
      and reduction: Report of the AAPM Therapy Physics Committee Task Group 180.
AB  - BACKGROUND: With radiotherapy having entered the era of image guidance, or image
      guided radiation therapy (IGRT), imaging procedures are routinely performed for
      patient positioning and target localization. The imaging dose delivered may
      result in excessive dose to sensitive organs and potentially increase the chance
      of secondary cancers and, therefore, needs to be managed. AIMS: This task group
      was charged with: a) providing an overview on imaging dose, including megavoltage
      electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR),
      Tomotherapy MV-CT, megavoltage cone-beam CT (MV-CBCT) and kilovoltage cone-beam
      CT (kV-CBCT), and b) providing general guidelines for commissioning dose
      calculation methods and managing imaging dose to patients. MATERIALS & METHODS:
      We briefly review the dose to radiotherapy (RT) patients resulting from different
      image guidance procedures and list typical organ doses resulting from MV and kV
      image acquisition procedures. RESULTS: We provide recommendations for managing
      the imaging dose, including different methods for its calculation, and techniques
      for reducing it. The recommended threshold beyond which imaging dose should be
      considered in the treatment planning process is 5% of the therapeutic target
      dose. DISCUSSION: Although the imaging dose resulting from current kV acquisition
      procedures is generally below this threshold, the ALARA principle should always
      be applied in practice. Medical physicists should make radiation oncologists
      aware of the imaging doses delivered to patients under their care. CONCLUSION:
      Balancing ALARA with the requirement for effective target localization requires
      that imaging dose be managed based on the consideration of weighing risks and
      benefits to the patient.

PMID- 29468679
TI  - Remote treatment of sleep-related trichotillomania and trichophagia.
AB  - We used a biobehavioral treatment consisting of melatonin and a standardized bed
      and wake time to decrease one girl's head and mouth touches associated with sleep
      related trichotillomania and trichophagia. We remotely coached the girl's
      caregiver to implement all procedures and monitored response to treatment using a
      DropCam Pro video camera equipped with night-vision capabilities. Head and mouth
      touches decreased, and her sleep pattern improved with the combination of
      treatment strategies. We discuss our use of a novel mode of service delivery to
      treat sleep-related problem behavior.

PMID- 29468680
TI  - Proinflammatory role of blister fluid-derived exosomes in bullous pemphigoid.
AB  - Bullous pemphigoid is an autoimmune inflammatory disorder characterized by the
      presence of autoantibodies against bullous pemphigoid autoantigens, leading to
      dermal-epidermal separation with consequent blister formation. However, whether
      and how the components of blister fluid exacerbate the progression of bullous
      pemphigoid is unclear. Exosomes are nanometre-sized vesicles released from cells
      into the body fluid, where they can transmit signals throughout the body. In the
      present study, we isolated and characterized exosomes from blister fluids of
      patients with bullous pemphigoid, evaluated their proinflammatory role, and
      identified the underlying molecular mechanisms. We found that exosomes isolated
      from blister fluids of patients with bullous pemphigoid showed the expected size
      and expressed the marker proteins CD63, CD81, and CD9. Additionally, blister
      fluid-derived exosomes were internalized by human primary keratinocytes, inducing
      the production of critical inflammatory cytokines and chemokines. Western
      blotting analysis showed robust and rapid activation of the extracellular signal
      regulated kinase 1/2 and signal transducer and activator of transcription 3
      signalling pathways in human primary keratinocytes after stimulation with blister
      fluid-derived exosomes. We also found that blister fluid-derived exosomes
      indirectly induced neutrophil trafficking by upregulating C-X-C motif chemokine
      ligand 8 in vitro. Furthermore, CD63 was localized mostly to keratinocytes and
      infiltrative granulocytes in skin lesions, suggesting that these cells were the
      possible sources of exosomes in blister fluid. Using mass spectrometry, we
      analysed the proteomes of blister fluid-derived exosomes and identified a variety
      of proteins implicated in inflammatory and immune responses. Together, our
      findings provide strong evidence that blister fluid-derived exosomes are involved
      in the local autoinflammatory responses of the skin associated with bullous
      pemphigoid. Copyright (c) 2018 Pathological Society of Great Britain and Ireland.
      Published by John Wiley & Sons, Ltd.

PMID- 29468681
TI  - Spatiotemporal distribution of small ubiquitin-like modifiers during human
      placental development and in response to oxidative and inflammatory stress.
AB  - KEY POINTS: The post-translational modification of target proteins by SUMOylation
      occurs in response to stressful stimuli in a variety of organ systems. Small
      ubiquitin-like modifier (SUMO) isoforms 1-4 have recently been identified in the
      human placenta, and are upregulated in the major obstetrical complication of pre
      eclampsia. This is the first study to characterize the spatiotemporal
      distribution of SUMO isoforms and their targets during placental development
      across gestation and in response to stress induced by pre-eclampsia and
      chorioamnionitis. Keratins were identified as major targets of placental
      SUMOylation. The interaction with SUMOs and cytoskeletal filaments provides
      evidence for SUMOylation possibly contributing to underlying dysfunctional
      trophoblast turnover, which is a hallmark feature of pre-eclampsia. Further
      understanding the role of individual SUMO isoforms and SUMOylation underlying
      placental dysfunction may provide a target for a novel therapeutic candidate as
      an approach for treating pre-eclampsia complicated with placental pathology.
      ABSTRACT: SUMOylation is a dynamic, reversible post-translational modification
      that regulates cellular protein stability and localization. SUMOylation occurs in
      response to various stressors, including hypoxia and inflammation, features
      common in the obstetrical condition of pre-eclampsia. SUMO isoforms 1-4 have
      recently been identified in the human placenta, but less is known about their
      role in response to pre-eclamptic stress. We hypothesized that SUMOylation
      components have a unique spatiotemporal distribution during placental development
      and that their subcellular localization can be further modulated by extra
      cellular stressors. Placental SUMO expression was examined across gestation.
      First-trimester human placental explants and JAR cells were subjected to hypoxia
      or TNF-alpha cytokine, and subcellular translocation of SUMOs was monitored.
      SUMOylation target proteins were elucidated using mass spectrometry and proximity
      ligation assay. Placental SUMO-1 and SUMO-4 were restricted to villous
      cytotrophoblast cells in first trimester and syncytium by term, while SUMO-2/3
      staining was evenly distributed throughout the trophoblast across gestation. In
      placental villous explants, oxidative stress induced hyperSUMOylation of SUMO-1
      and SUMO-4 in the syncytial cytoplasm, whereas SUMO-2/3 nuclear expression
      increased. Oxidative stress also upregulated cytoplasmic SUMO-1 and SUMO-4
      protein expression (P < 0.05), similar to pre-eclamptic placentas. Keratins were
      identified as major targets of placental SUMOylation. Oxidative stress increased
      the cytokeratin-7 to SUMO-1 and SUMO-4 interactions, while inflammatory stress
      increased its interaction with SUMO-2/3. Overall, SUMOs display a unique
      spatiotemporal distribution in normal human placental development. Our data
      indicate SUMOylation in pre-eclampsia, which may impair the stability of
      cytoskeleton filaments and thus promote trophoblast shedding into the maternal
      circulation in this condition.

PMID- 29468682
TI  - Factors associated with the desire for companionship during labor in a Nigerian
      community.
AB  - OBJECTIVE: To determine preferences for companionship during labor and to
      identify associated factors. METHODS: The present prospective cross-sectional
      survey was conducted at a university teaching hospital in Nigeria between
      September 1, 2011, and February 28, 2012. Participants included women who
      underwent the first stage of labor and delivery at the facility, male partners,
      and healthcare workers from the maternity unit. Data were collected using a
      pretested questionnaire. RESULTS: There were 226 parturients, 158 male partners,
      and 69 healthcare workers included in the final analysis; in all, 50 (22.1%)
      parturients and 37 (23.4%) male partners approved of companionship during labor,
      whereas 62 (90%) healthcare workers supported it. Among those who approved, a
      parturient's male partner was stated to be the preferred companion by 33 (66%)
      parturients, 32 (86%) male partners, and 58 (94%) healthcare workers. The
      perception of conduciveness of the labor ward for companionship was associated
      with approving of companionship among both the parturients (adjusted odds ratio
      [aOR] 2.74) and male partners (aOR 15.79). Previous home delivery (aOR 31.43) and
      companionship during a previous delivery (aOR 23.00) were also associated with
      approval. CONCLUSION: Most couples had negative attitudes toward companionship
      during labor. Intensive education programs and restructuring of facilities could
      enable Nigerian labor wards to improve the delivery experience for both
      parturients and their male partners.

PMID- 29468683
TI  - Quantification of complex modular architecture in plants.
AB  - Morphometrics, the assignment of quantities to biological shapes, is a powerful
      tool to address taxonomic, evolutionary, functional and developmental questions.
      We propose a novel method for shape quantification of complex modular
      architecture in thalloid plants, whose extremely reduced morphologies, combined
      with the lack of a formal framework for thallus description, have long rendered
      taxonomic and evolutionary studies extremely challenging. Using graph theory,
      thalli are described as hierarchical series of nodes and edges, allowing for
      accurate, homologous and repeatable measurements of widths, lengths and angles.
      The computer program MorphoSnake was developed to extract the skeleton and
      contours of a thallus and automatically acquire, at each level of organization,
      width, length, angle and sinuosity measurements. Through the quantification of
      leaf architecture in Hymenophyllum ferns (Polypodiopsida) and a fully worked
      example of integrative taxonomy in the taxonomically challenging thalloid
      liverwort genus Riccardia, we show that MorphoSnake is applicable to all ramified
      plants. This new possibility of acquiring large numbers of quantitative traits in
      plants with complex modular architectures opens new perspectives of applications,
      from the development of rapid species identification tools to evolutionary
      analyses of adaptive plasticity.

PMID- 29468684
TI  - Re-evaluation of the regulation of omeprazole in racehorses: An evidence-based
      approach.
AB  - Medication control and doping control have been established in horse racing to
      ensure the integrity of the sport and the welfare of the horses. This ensures
      that horses do not compete under the influence of any drugs, including
      omeprazole, a therapeutic medication used to treat equine gastric ulcer syndrome.
      In this study, pharmacokinetic data were produced in equine plasma and urine
      following an oral administration of 4 mg/kg of generic buffered formulation of
      omeprazole to six Thoroughbred horses in five daily doses to determine an
      appropriate screening limit and detection time in equine plasma and to assess
      whether the current detection time of 72 hr in equine urine would be applicable
      when an alternative omeprazole product is administered. Cmax of 436-2,432 ng/ml
      and AUC0-tau of 1,476-4,371 ng hr ml-1 were obtained for plasma and indicated, in
      conjunction with other published oral omeprazole studies, that an appropriate
      plasma screening limit would be 500 pg/ml with a detection time of 48 hr. Urine
      analysis showed that omeprazole could be detected for up to 25 hr above the
      previously established urine screening limit of 500 pg/ml and thus indicated that
      the detection time advice could be potentially reduced from 72 to 48 hr to allow
      more comprehensive treatment of gastric lesions.

PMID- 29468685
TI  - A rapid cycle method for local adaptation of an obstetric emergencies training
      program.
AB  - OBJECTIVE: To describe the adaptation of an obstetric emergencies training
      program to align with local clinical practice. METHODS: A feasibility study was
      conducted to investigate the potential implementation of the PRactical Obstetric
      Multi-Professional Training (PROMPT) program at eight urban tertiary hospitals in
      the Philippines. Multi-professional teams attended a 2-day course on September 23
      and 24, 2015, that comprised a demonstration PROMPT course (day 1) and a Train
      the-Trainers session (day 2). During a facilitated adaptation session, each team
      reviewed the PROMPT algorithms for eclampsia, severe pre-eclampsia, postpartum
      hemorrhage and sepsis. The teams marked steps concordant with local practice and
      identified differences with local practice. Suggested amendments were reviewed by
      the PROMPT project team, using clinical guidelines to support any adaptations.
      RESULTS: The PROMPT algorithm for initial management of eclampsia was used as an
      exemplar. Five of the nine management steps were concordant with local practice:
      support; airway; breathing; circulation; and control seizures. Amendments were
      successfully implemented for the following steps: call for help; magnesium
      sulfate loading dose; and magnesium sulfate maintenance dose. CONCLUSION: Rapid
      and efficient adaptation of PROMPT training materials for use in the Philippines
      was possible using a facilitated and focused approach, utilizing the expertise of
      a representative mix of local healthcare professionals and evidence-based
      guidelines.

PMID- 29468686
TI  - Token reinforcement: Translational research and application.
AB  - The present paper provides an integrative review of research on token
      reinforcement systems, organized in relation to basic behavioral functions and
      economic variables. This type of functional taxonomy provides a useful way to
      organize the literature, bringing order to a wide range of findings across
      species and settings, and revealing gaps in the research and areas especially
      ripe for analysis and application. Unlike standard translational research, based
      on a unidirectional model in which the analysis moves from laboratory to the
      applied realm, work in the area of token systems is best served by a
      bidirectional interplay between laboratory and applied research, where applied
      questions inspire research on basic mechanisms. When based on and contributing to
      an analysis, applied research on token economies can be on the leading edge of
      theoretical advances, helping set the scientific research agenda.

PMID- 29468688
TI  - Polymorphisms of cytochrome P450 2B6 (CYP2B6) in cynomolgus and rhesus macaques.
AB  - BACKGROUND: Cytochrome P450 2B6 (CYP2B6) is an important drug-metabolizing enzyme
      and is expressed in liver. Although human CYP2B6 variants account for variable
      enzyme properties among individuals and populations, CYP2B6 genetic variants have
      not been investigated in cynomolgus macaques, widely used in drug metabolism
      studies. METHODS: CYP2B6 was resequenced in 120 cynomolgus macaques and 23 rhesus
      macaques by direct sequencing. RESULTS: Twenty-three non-synonymous variants were
      found, of which 12 and 3 were unique to cynomolgus macaques and rhesus macaques,
      respectively. By functional characterization using the 14 variant proteins, 8
      variants (V114I, R253C, M435I, V459M, L465P, C475S, R487C, and R487H) showed
      different rate (>1.5-fold) of testosterone 16beta-hydroxylation to wild type.
      However, the four variants (M435I, L465P, C475S, and R487H) were analyzed in
      liver microsomes, and the catalytic rates were not substantially different from
      wild type. CONCLUSIONS: Macaque CYP2B6 was polymorphic, and the genotype could
      partly account for variable enzyme activities of macaque CYP2B6.

PMID- 29468687
TI  - Genome-wide association mapping of the architecture of susceptibility to the root
      knot nematode Meloidogyne incognita in Arabidopsis thaliana.
AB  - Susceptibility to the root-knot nematode Meloidogyne incognita in plants is
      thought to be a complex trait based on multiple genes involved in cell
      differentiation, growth and defence. Previous genetic analyses of susceptibility
      to M. incognita have mainly focused on segregating dominant resistance genes in
      crops. It is not known if plants harbour significant genetic variation in
      susceptibility to M. incognita independent of dominant resistance. To study the
      genetic architecture of susceptibility to M. incognita, we analysed nematode
      reproduction on a highly diverse set of 340 natural inbred lines of Arabidopsis
      thaliana with genome-wide association mapping. We observed a surprisingly large
      variation in nematode reproduction among these lines. Genome-wide association
      mapping revealed four quantitative trait loci (QTLs) located on chromosomes 1 and
      5 of A. thaliana significantly associated with reproductive success of M.
      incognita, none of which harbours typical resistance gene homologues. Mutant
      analysis of three genes located in two QTLs showed that the transcription factor
      BRASSINAZOLE RESISTANT1 and an F-box family protein may function as (co
      )regulators of susceptibility to M. incognita in Arabidopsis. Our data suggest
      that breeding for loss-of-susceptibility, based on allelic variants critically
      involved in nematode feeding, could be used to make crops more resilient to root
      knot nematodes.

PMID- 29468689
TI  - A novel variant B allele at the ABO gene locus characterized by a duplication
      based insertion of 27 nucleotides identified in an Iraqi male with a weak B
      subgroup phenotype.

PMID- 29468691
TI  - V: GENERAL DISCUSSION.

PMID- 29468692
TI  - ADVANCES IN THE ASSESSMENT OF YOUNG BILINGUALS: COMMENTS ON FLOCCIA ET AL.
AB  - In this article, we comment on the significant contributions to science and to
      clinical practice made by Floccia et al.'s study of over 400 bilingual 2-year-old
      children. To science, this work contributes new findings on the linguistic
      factors that make some pairs of languages easier to learn than others and rich
      data on the environmental factors that influence bilingual development. Their
      results provide clues to the nature of the language learning process. To clinical
      practice, Floccia et al. contribute a new instrument for the diagnosis of risk
      for language impairment in bilingual children and a new method for the
      development of assessment instruments more generally. The experience-adjusted
      approach to norming that they illustrate here provides an example for others to
      follow. Their method holds promise for test development in many domains where the
      goal is to assess children's internal capacity but the evidence that is available
      in children's achievement is systematically influenced by environmental factors.

PMID- 29468690
TI  - Lost in diversity: the interactions between soil-borne fungi, biodiversity and
      plant productivity.
AB  - There is consensus that plant species richness enhances plant productivity within
      natural grasslands, but the underlying drivers remain debated. Recently,
      differential accumulation of soil-borne fungal pathogens across the plant
      diversity gradient has been proposed as a cause of this pattern. However, the
      below-ground environment has generally been treated as a 'black box' in
      biodiversity experiments, leaving these fungi unidentified. Using next generation
      sequencing and pathogenicity assays, we analysed the community composition of
      root-associated fungi from a biodiversity experiment to examine if evidence
      exists for host specificity and negative density dependence in the interplay
      between soil-borne fungi, plant diversity and productivity. Plant species were
      colonised by distinct (pathogenic) fungal communities and isolated fungal species
      showed negative, species-specific effects on plant growth. Moreover, 57% of the
      pathogenic fungal operational taxonomic units (OTUs) recorded in plant
      monocultures were not detected in eight plant species plots, suggesting a loss of
      pathogenic OTUs with plant diversity. Our work provides strong evidence for host
      specificity and negative density-dependent effects of root-associated fungi on
      plant species in grasslands. Our work substantiates the hypothesis that fungal
      root pathogens are an important driver of biodiversity-ecosystem functioning
      relationships.

PMID- 29468693
TI  - II: METHODS.

PMID- 29468694
TI  - IV: RESULTS FOR STUDIES 2 AND 3: THE UKBTAT MODEL AND ITS APPLICATION TO
      NONTARGET ADDITIONAL LANGUAGE LEARNERS.

PMID- 29468696
TI  - I: INTRODUCTION.
AB  - The majority of the world's children grow up learning two or more languages. The
      study of early bilingualism is central to current psycholinguistics, offering
      insights into issues such as transfer and interference in development. From an
      applied perspective, it poses a universal challenge to language assessment
      practices throughout childhood, as typically developing bilingual children
      usually underperform relative to monolingual norms when assessed in one language
      only. We measured vocabulary with Communicative Development Inventories for 372
      24-month-old toddlers learning British English and one Additional Language out of
      a diverse set of 13 (Bengali, Cantonese, Dutch, French, German, Greek, Hindi
      Urdu, Italian, Mandarin, Polish, Portuguese, Spanish, and Welsh). We furthered
      theoretical understanding of bilingual development by showing, for the first
      time, that linguistic distance between the child's two languages predicts
      vocabulary outcome, with phonological overlap related to expressive vocabulary,
      and word order typology and morphological complexity related to receptive
      vocabulary, in the Additional Language. Our study also has crucial clinical
      implications: we have developed the first bilingual norms for expressive and
      receptive vocabulary for 24-month-olds learning British English and an Additional
      Language. These norms were derived from factors identified as uniquely predicting
      CDI vocabulary measures: the relative amount of English versus the Additional
      Language in child-directed input and parental overheard speech, and infant
      gender. The resulting UKBTAT tool was able to accurately predict the English
      vocabulary of an additional group of 58 bilinguals learning an Additional
      Language outside our target range. This offers a pragmatic method for the
      assessment of children in the majority language when no tool exists in the
      Additional Language. Our findings also suggest that the effect of linguistic
      distance might extend beyond bilinguals' acquisition of early vocabulary to
      encompass broader cognitive processes, and could constitute a key factor in the
      study of the debated bilingual advantage.

PMID- 29468697
TI  - III: ANALYSES AND RESULTS FOR STUDY 1: ESTIMATING THE EFFECT OF LINGUISTIC
      DISTANCE ON VOCABULARY DEVELOPMENT.

PMID- 29468698
TI  - Systematic review: non A-E, seronegative or indeterminate hepatitis; what is this
      deadly disease?
AB  - BACKGROUND: A significant proportion of cases of acute liver failure (ALF) do not
      have an identifiable cause; so called "non A-E," "non A, non B, non C,"
      "seronegative" or "indeterminate" hepatitis. However, this entity is clinically
      not well described. AIM: To collate the known incidence and outcomes in
      indeterminate hepatitis. This systematic review sought to identify potential
      aetiologies that ought to be considered, and identify likely future objectives in
      classification and treatment strategies for indeterminate hepatitis. METHODS:
      Literature review to determine aetiological factors, prevalence and outcomes
      relating to indeterminate hepatitis. RESULTS: There is significant heterogeneity
      within the reported cases of indeterminate hepatitis in the literature. Some of
      the potential infective aetiologies which are reviewed here include: parvovirus
      B19 (PVB19), herpes simplex virus (HSV), Toga-Like Virus and the Annelloviridae
      (including SEN-V). Interestingly, this condition predominately affects middle
      aged women, with subacute progression of the liver failure. In addition, the
      prognosis of indeterminate hepatitis is poor, with reduced spontaneous survival
      compared with other causes of acute liver failure and increased need for
      emergency liver transplantation. CONCLUSIONS: Whilst various pathological
      processes have been implicated in the development of indeterminate hepatitis, the
      specific cause remains elusive. There is an urgent need for general consensus on
      a specific definition and exclusion of confounding aetiologies with coordinated
      multicentre investigation of this rare condition to identify aetiology and
      develop therapies to reduce the significant mortality and need for emergency
      liver transplantation associated with this condition.

PMID- 29468699
TI  - Retracted: Early diabetic retinopathy diagnosis based on local retinal blood
      vessels analysis in optical coherence tomography angiography (OCTA) images.
AB  - The above article from Medical Physics, published online on 22 February 2018 in
      Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement
      between the authors, the journal Editor in Chief and John Wiley & Sons Ltd. The
      retraction has been agreed following an investigation carried out by the editors
      due to major overlap with a previously published article: British Journal of
      Ophthalmology (BJO) (Sandhu HS, Eladawi N, Elmogy M, et al Automated diabetic
      retinopathy detection using optical coherence tomography angiography: a pilot
      study, British Journal of Ophthalmology Published Online First: 23 January 2018.
      doi:10.1136/bjophthalmol-2017-311489.

PMID- 29468700
TI  - Cancer cells govern miR-2909 exosomal recruitment through its 3'-end post
      transcriptional modification.
AB  - It is widely believed that selective packaging of nucleic acids, especially
      microRNAs, into exosomes secreted by the cancer cells not only ensures their
      growth and survival but also helps in the escape from immune surveillance.
      Keeping in view the fact that human cellular miR-2909 has emerged to regulate
      genes involved in oncogenesis and immunity, the present study was addressed to
      reveal the nature of miR-2909 expression within cancer cells of different tissue
      origin and its incorporation into exosomes secreted by these cells. Post
      transcriptional modification, especially 3'-end adenylation and uridylation of
      miR-2909, exerts opposing effects that may contribute to direct its sorting into
      exosomes secreted by cancer cells. Our study also revealed that selective
      partitioning of adenosine kinase, between cancer cells and their secreted
      exosomes, may be responsible for the nature of post-transcriptional modification
      of miR-2909 observed within these cells.

PMID- 29468701
TI  - Randomised clinical trial: efficacy, safety and dosage of adjunctive allopurinol
      in azathioprine/mercaptopurine nonresponders (AAA Study).
AB  - BACKGROUND: Thiopurine hypermethylation towards 6-methylmercaptopurine (6MMP)
      instead of 6-thioguanine nucleotides (6TGN) is associated with inefficacy in
      patients with IBD. Allopurinol reverses such hypermethylation. AIMS: To
      prospectively determine efficacy of allopurinol-thiopurine combination and to
      compare 2 doses of allopurinol. DESIGN: In a multicentre, double-blind trial,
      patients with clinically active or steroid-dependent IBD and thiopurine shunting
      were randomised to 50 or 100 mg/d allopurinol and 25% of their screening
      thiopurine dose, which was subsequently optimised, aiming for 6TGN of 260-500
      pmol/8x108 RBCs. The primary endpoint was steroid-free clinical remission at 24
      weeks. RESULTS: Of 73 patients, 39 (53% [95% CI 42-65]) achieved steroid-free
      remission, (54% with 50 mg/d and 53% with 100 mg/d). 81% were able to discontinue
      steroids. Therapeutic 6TGN levels were achieved in both groups. Final thiopurine
      doses were lower with 100 mg/d allopurinol (P < 0.005). 6MMP: 6TGN ratio
      decreased from mean 64 to 4 (P < 0.001), being higher with 50 mg/d (6 +/- 1.83)
      than for 100 mg/d ([1 +/- 0.16], P = 0.003). Three patients on 50 mg/d failed to
      sustain low ratios at 24 weeks. Toxicity was minimal; three patients on 50 mg/d
      allopurinol developed transient leukopenia. Alanine aminotransferase
      concentrations decreased (P < 0.001) similarly in both arms. Faecal calprotectin
      levels at study end were lower in patients who achieved the primary endpoint
      (median 171 [85-541] vs 821[110-5892] ug/g, P = 0.03). CONCLUSIONS: Low-dose
      allopurinol-thiopurine combination safely reverses shunting and optimises 6TGN
      with associated improvement in disease activity. 100 mg/d allopurinol is
      preferable due to greater metabolite profile stability and lower thiopurine dose
      without additional toxicity.

PMID- 29468702
TI  - Identifying optimal dosage regimes under safety constraints: An application to
      long term opioid treatment of chronic pain.
AB  - There is growing interest and investment in precision medicine as a means to
      provide the best possible health care. A treatment regime formalizes precision
      medicine as a sequence of decision rules, one per clinical intervention period,
      that specify if, when and how current treatment should be adjusted in response to
      a patient's evolving health status. It is standard to define a regime as optimal
      if, when applied to a population of interest, it maximizes the mean of some
      desirable clinical outcome, such as efficacy. However, in many clinical settings,
      a high-quality treatment regime must balance multiple competing outcomes; eg,
      when a high dose is associated with substantial symptom reduction but a greater
      risk of an adverse event. We consider the problem of estimating the most
      efficacious treatment regime subject to constraints on the risk of adverse
      events. We combine nonparametric Q-learning with policy-search to estimate a high
      quality yet parsimonious treatment regime. This estimator applies to both
      observational and randomized data, as well as settings with variable, outcome
      dependent follow-up, mixed treatment types, and multiple time points. This work
      is motivated by and framed in the context of dosing for chronic pain; however,
      the proposed framework can be applied generally to estimate a treatment regime
      which maximizes the mean of one primary outcome subject to constraints on one or
      more secondary outcomes. We illustrate the proposed method using data pooled from
      5 open-label flexible dosing clinical trials for chronic pain.

PMID- 29468703
TI  - Individual differences in social control: Who 'speaks up' when witnessing
      uncivil, discriminatory, and immoral behaviours?
AB  - This research examined the personality characteristics of individuals who 'speak
      up' and confront perpetrators of norm transgressions. We tested whether those who
      intervene tend to be 'bitter complainers' or 'well-adjusted leaders'. In four
      studies (total N = 1,003), we measured several individual differences that are
      directly implicated by at least one of the two concepts. We also presented
      participants with uncivil, discriminatory, and immoral behaviours and asked them
      how likely they would be to intervene if they were to witness each of these
      behaviours as a bystander. The results confirmed the well-adjusted leader
      hypothesis: Participants' self-reported tendency to confront perpetrators
      correlated positively with altruism, extraversion, social responsibility,
      acceptance by peers, independent self-construal, emotion regulation, persistence,
      self-directedness, age, occupation, and monthly salary, but not with
      aggressiveness or low self-esteem. Individuals who confront prejudice also speak
      up against other immoral and uncivil behaviours. We discuss the implications of
      these findings for the perpetuation and change of social norms.

PMID- 29468704
TI  - Nerve alterations showing autophagy in 2 patients with lichen aureus.
AB  - Lichen aureus is a rare, chronic, persistent purpuric dermatosis clinically
      characterized by striking yellow- to bronze-colored lesions. Histologically,
      lichen aureus differs from other pigmented purpuric dermatoses in containing
      dense, band-like infiltrates closely associated with the epidermis. This report
      describes 2 patients with lichen aureus, a 20-year-old woman with a lesion on her
      right arm and a 51-year-old man with a lesion on the right side of his groin.
      Skin biopsy specimens revealed almost identical findings in both patients,
      including dense band-like infiltrates containing lymphocytes, histiocytes with
      hemosiderin deposits scattered extravasated red blood cells and nerve alterations
      at the dermo-epidermal interface. The nerves within the lesions were filled with
      granules, which stained positive with antibody to microtubule-associated protein
      1A/1B-light chain 3, suggesting autophagy within the nerves. These altered nerves
      were present only in areas of band-like dermal lymphocytic infiltration. Electron
      microscopy of the lesions showed the accumulation of autophagosomes in Schwann
      cells.

PMID- 29468705
TI  - Low risk of hepatotoxicity from rifampicin when used for cholestatic pruritus: a
      cross-disease cohort study.
AB  - BACKGROUND: The use of rifampicin for cholestatic pruritus is accompanied by
      concerns over safety, but the availability of real-world prescribing data is
      relatively limited. AIM: We sought to describe the rate and characteristics of
      rifampicin-induced hepatitis in a mixed aetiology cohort of patients with
      established liver disease and cholestatic pruritus. METHODS: Retrospective review
      of records for out-patients commenced on rifampicin for pruritus 2012-2016
      inclusive. Rifampicin-induced hepatitis was recorded where alanine
      aminotransferase activity (ALT) increased to both >=5 * baseline and >=5 * upper
      limit of normal (ULN), or to both >=3 * baseline and >=3 * ULN with concurrent
      elevation in serum bilirubin to >=2 * baseline and >=2 * ULN, in addition to a
      Roussel-Uclaf Causality Assessment Method score of "probable" or "highly
      probable" for rifampicin causality. RESULTS: After exclusions, we reviewed 105
      patients who took rifampicin for a median of 131 days. Most had primary biliary
      cholangitis or primary sclerosing cholangitis; 40 (38.1%) were men and median age
      was 44 years (IQR: 32-57). 44 (41.9%) patients had baseline serum bilirubin >=2 *
      ULN and 28 (26.7%) ALT >=3 * ULN. 5 (4.8%) developed rifampicin-induced hepatitis
      at a median of 70(range 27-130) days after drug initiation. No individual or
      laboratory baseline characteristics were significantly associated with subsequent
      development of hepatitis. All cases of hepatitis recovered after drug cessation,
      although one patient was hospitalised and received corticosteroids. CONCLUSIONS:
      Given the efficacy of rifampicin for an important sub-group of those with
      cholestatic pruritus, adult patients, including those with jaundice, can be
      counselled that 95% of prescriptions are safe, and where hepatitis occurs,
      including at long latency, drug cessation appears effective.

PMID- 29468706
TI  - Comparative cardiovascular safety of nonsteroidal anti-inflammatory drugs in
      patients with hypertension: a population-based cohort study.
AB  - AIMS: Previous studies have suggested that nonsteroidal anti-inflammatory drugs
      (NSAIDs) may be associated with higher cardiovascular risks. However, few have
      been active comparison studies that directly assessed the potential differential
      cardiovascular risk between NSAID classes or across individual NSAIDs. We
      compared the risk of major cardiovascular events between cyclooxygenase 2 (COX-2)
      selective and nonselective NSAIDs in patients with hypertension. METHODS: We
      conducted a cohort study of patients with hypertension who initiated COX-2
      selective or nonselective NSAIDs in a population-based Taiwanese database. The
      outcomes included hospitalization for the following major cardiovascular events:
      ischaemic stroke, acute myocardial infarction, congestive heart failure,
      transient ischaemic attack, unstable angina or coronary revascularization. We
      followed patients for up to 4 weeks, based on the as-treated principle. We used
      inverse probability weighting to control for baseline and time-varying
      covariates, and estimated the on-treatment hazard ratios (HRs) and 95%
      conservative confidence interval (CIs). RESULTS: We identified 2749 eligible COX
      2-selective NSAID users and 52 880 eligible nonselective NSAID users. The HR of
      major cardiovascular events comparing COX-2-selective with nonselective NSAIDs
      after adjusting for baseline and time-varying covariates was 1.07 (95% CI 0.65,
      1.74). We did not observe a differential risk when comparing celecoxib to
      diclofenac (HR 1.17; 95% CI 0.61, 2.25), ibuprofen (HR 1.36; 95% CI 0.58, 3.18)
      or naproxen (HR 0.75; 95% CI 0.23, 2.44). There was an increased risk with COX-2
      selective NSAIDs, however, when comparing COX-2-selective NSAIDs with mefenamic
      acid (HR 2.11; 95% CI 1.09, 4.09). CONCLUSIONS: Our results provide important
      information about the comparative cardiovascular safety of NSAIDs in patients
      with hypertension.

PMID- 29468707
TI  - A truth that does not always speak its name: How Hollander and Turowetz's
      findings confirm and extend the engaged followership analysis of harm-doing in
      the Milgram paradigm.
AB  - Hollander and Turowetz (2017, Br. J. Soc. Psychol., 56, 655-674) present
      important data from post-experimental interviews with participants in Milgram's
      'obedience' research. In these, participants responded to various questions about
      their perceptions of the study and their behaviour by indicating that they
      trusted the Experimenter not to let them inflict serious harm. Relatively few
      participants indicated that they acted as they did because they were committed to
      the Experimenter or to science. We argue, however, that there are two key reasons
      why this evidence is not inconsistent with claims that harm-doing is a product of
      engaged followership. The first is that (in contrast to the data obtained from
      later post-experimental surveys) the conversational logic of the interviews does
      not topicalize a discussion or valorization of science, but instead requires
      participants to defend themselves against an accusation of improper behaviour.
      The second is that participants' accounts of their behaviour nevertheless
      revolved around expressions of trust in the Experimenter which can themselves be
      seen as manifestations of shared identity and engaged followership. Nevertheless,
      we argue that H&T's analysis points to significant ways in which the engaged
      followership account and its broader implications for understanding perpetrator
      behaviour can be embellished.

PMID- 29468708
TI  - Development and clinical application of an evidence-based pharmaceutical care
      service algorithm in acute coronary syndrome.
AB  - WHAT IS KNOWN AND OBJECTIVE: Drug therapies are critical for preventing secondary
      complications in acute coronary syndrome (ACS). The purpose of this study was to
      develop and apply a pharmaceutical care service (PCS) algorithm for ACS and
      confirm that it is applicable through a prospective clinical trial. METHODS: The
      ACS-PCS algorithm was developed according to extant evidence-based treatment and
      pharmaceutical care guidelines. Quality assurance was conducted through two
      methods: literature comparison and expert panel evaluation. The literature
      comparison was used to compare the content of the algorithm with the referenced
      guidelines. Expert evaluations were conducted by nine experts for 75
      questionnaire items. A trial was conducted to confirm its effectiveness. Seventy
      nine patients were assigned to either the pharmacist-included multidisciplinary
      team care (MTC) group or the usual care (UC) group. The endpoints of the trial
      were the prescription rate of two important drugs, readmission, emergency room
      (ER) visit and mortality. RESULTS AND DISCUSSION: The main frame of the algorithm
      was structured with three tasks: medication reconciliation, medication
      optimization and transition of care. The contents and context of the algorithm
      were compliant with class I recommendations and the main service items from the
      evidence-based guidelines. Opinions from the expert panel were mostly positive.
      There were significant differences in beta-blocker prescription rates in the
      overall period (P = .013) and ER visits (four cases, 9.76%, P = .016) in the MTC
      group compared to the UC group, respectively. WHAT IS NEW AND CONCLUSION: We
      developed a PCS algorithm for ACS based on the contents of evidence-based drug
      therapy and the core concept of pharmacist services.

PMID- 29468709
TI  - Multiple perineuriomatous melanocytic nevi.
AB  - Perineuriomatous differentiation in solitary cutaneous melanocytic nevi has been
      described. We present an unusual case of a patient with multiple such
      perineuriomatous nevi. This presentation raises the possibility that a germline
      mutation may be responsible for the pathogenesis of these unusual lesions.

PMID- 29468710
TI  - Variable selection with group structure in competing risks quantile regression.
AB  - We study the group bridge and the adaptive group bridge penalties for competing
      risks quantile regression with group variables. While the group bridge
      consistently identifies nonzero group variables, the adaptive group bridge
      consistently selects variables not only at group level but also at within-group
      level. We allow the number of covariates to diverge as the sample size increases.
      The oracle property for both methods is also studied. The performance of the
      group bridge and the adaptive group bridge is compared in simulation and in a
      real data analysis. The simulation study shows that the adaptive group bridge
      selects nonzero within-group variables more consistently than the group bridge. A
      bone marrow transplant study is provided as an example.

PMID- 29468711
TI  - Estimating recurrence and incidence of preterm birth subject to measurement error
      in gestational age: A hidden Markov modeling approach.
AB  - Prediction of preterm birth as well as characterizing the etiological factors
      affecting both the recurrence and incidence of preterm birth (defined as
      gestational age at birth <= 37 wk) are important problems in obstetrics. The
      National Institute of Child Health and Human Development (NICHD) consecutive
      pregnancy study recently examined this question by collecting data on a cohort of
      women with at least 2 pregnancies over a fixed time interval. Unfortunately,
      measurement error due to the dating of conception may induce sizable error in
      computing gestational age at birth. This article proposes a flexible approach
      that accounts for measurement error in gestational age when making inference. The
      proposed approach is a hidden Markov model that accounts for measurement error in
      gestational age by exploiting the relationship between gestational age at birth
      and birth weight. We initially model the measurement error as being normally
      distributed, followed by a mixture of normals that has been proposed on the basis
      of biological considerations. We examine the asymptotic bias of the proposed
      approach when measurement error is ignored and also compare the efficiency of
      this approach to a simpler hidden Markov model formulation where only gestational
      age and not birth weight is incorporated. The proposed model is compared with
      alternative models for estimating important covariate effects on the risk of
      subsequent preterm birth using a unique set of data from the NICHD consecutive
      pregnancy study.

PMID- 29468712
TI  - New insights in Type I and II CD20 antibody mechanisms-of-action with a panel of
      novel CD20 antibodies.
AB  - Based on their mechanisms-of-action, CD20 monoclonal antibodies (mAbs) are
      grouped into Type I [complement-dependent cytotoxicity (CDC) and antibody
      dependent cell-mediated cytotoxicity (ADCC)] and Type II [programmed cell death
      (PCD) and ADCC] mAbs. We generated 17 new hybridomas producing CD20 mAbs of
      different isotypes and determined unique heavy and light chain sequence pairs for
      13 of them. We studied their epitope binding, binding kinetics and structural
      properties and investigated their predictive value for effector functions, i.e.
      PCD, CDC and ADCC. Peptide mapping and CD20 mutant screens revealed that 10 out
      of these 11 new mAbs have an overlapping epitope with the prototypic Type I mAb
      rituximab, albeit that distinct amino acids of the CD20 molecule contributed
      differently. Binding kinetics did not correlate with the striking differences in
      CDC activity among the mIgG2c mAbs. Interestingly, chimerization of mAb m1
      resulted in a mAb displaying both Type I and II characteristics. PCD induction
      was lost upon introduction of a mutation in the framework of the heavy chain
      affecting the elbow angle, supporting that structural changes within this region
      can affect functional activities of CD20 mAbs. Together, these new CD20 mAbs
      provide further insights in the properties dictating the functional efficacy of
      CD20 mAbs.

PMID- 29468713
TI  - Granulomatous and lichenoid dermatitis after IgG4 anti-PD-1 monoclonal antibody
      therapy for advanced cancer.
AB  - Nivolumab is a fully human IgG4 monoclonal antibody directed against programmed
      cell death protein 1 (PD-1). PD-1 inhibition allows T-cell activation and
      recruitment to destroy cancer cells. Checkpoint inhibitors have shown significant
      survival advantage and relatively low side-effects in comparison with
      conventional chemotherapy in several types of advanced cancer. Granulomatous
      cutaneous reactions have been reported showing sarcoidal and panniculitic
      morphology. Here we present a case of drug-induced lichenoid and granulomatous
      dermatitis after checkpoint inhibitor therapy observed in a 63-year-old male
      treated with nivolumab for advanced glioblastoma. This morphology has not been
      previously reported. We documented a high number of CD8+ T-cells within the
      lesions. Additionally, we review the side-effects observed with the use of
      checkpoint inhibitors, with special focus on cutaneous manifestations.

PMID- 29468714
TI  - Consistent gaussian basis sets of double- and triple-zeta valence with
      polarization quality of the fifth period for solid-state calculations.
AB  - Consistent basis sets of double- and triple-zeta valence with polarization
      quality for the fifth period have been derived for periodic quantum-chemical
      solid-state calculations with the crystalline-orbital program CRYSTAL. They are
      an extension of the pob-TZVP basis sets, and are based on the full-relativistic
      effective core potentials (ECPs) of the Stuttgart/Cologne group and on the def2
      SVP and def2-TZVP valence basis of the Ahlrichs group. We optimized orbital
      exponents and contraction coefficients to supply robust and stable self
      consistent field (SCF) convergence for a wide range of different compounds. The
      computed crystal structures are compared to those obtained with standard basis
      sets available from the CRYSTAL basis set database. For the applied hybrid
      density functional PW1PW, the average deviations of calculated lattice constants
      from experimental references are smaller with pob-DZVP and pob-TZVP than with
      standard basis sets. (c) 2018 Wiley Periodicals, Inc.

PMID- 29468715
TI  - Clinical safety, tolerability, pharmacokinetics and effects on urinary
      electrolyte excretion of AZD9977, a novel, selective mineralocorticoid receptor
      modulator.
AB  - AIMS: AZD9977 is the first mineralocorticoid receptor modulator in clinical
      development exerting similar organ protection as eplerenone with minimal urinary
      electrolyte effects in preclinical studies. The aim was to perform the initial
      clinical assessment of AZD9977. METHODS: A first-in-human trial explored doses
      from 5 to 1200 mg. To study effects on urinary electrolyte excretion an
      additional randomized placebo controlled cross-over four-period clinical trial
      was performed. Twenty-three healthy volunteers were administered fludrocortisone
      alone or in combination with AZD9977, eplerenone or both. AZD9977/eplerenone
      combination was given to assess if AZD9977 can attenuate eplerenone induced
      natriuresis. RESULTS: AZD9977 at doses from 5 to 1200 mg was safe and well
      tolerated and pharmacokinetics were compatible with further development. AZD9977
      exhibited similar effects on urinary ln [Na+ ]/[K+ ] as eplerenone when using
      fludrocortisone as mineralocorticoid receptor agonist, and the combination had an
      additive effect on ln [Na+ K+ ]. CONCLUSIONS: The results in man contradict the
      results in rodent models driven by aldosterone, in which AZD9977 has minimal
      electrolyte effects. Future clinical studies with AZD9977 should be performed in
      presence of endogenous or exogenous aldosterone to assess potential benefit of
      AZD9977 in patients.

PMID- 29468716
TI  - Estimation of age effect with change-points on survival of cancer patients.
AB  - There is a global trend that the average onset age of many human complex diseases
      is decreasing, and the age of cancer patients becomes more spread out. The age
      effect on survival is nonlinear in practice and may have one or more important
      change-points at which the trend of the effect can be very different before and
      after these threshold ages. Identification of these change-points allows clinical
      researchers to understand the biologic basis for the complex relation between age
      and prognosis for optimal prognostic decision. This paper considers estimation of
      the potentially nonlinear age effect for general partly linear survival models to
      ensure a valid statistical inference on the treatment effect. A simple and
      efficient sieve maximum likelihood estimation method that can be implemented
      easily using standard statistical software is proposed. A data-driven adaptive
      algorithm to determine the optimal location and the number of knots for the
      identification of the change-points is suggested. Simulation studies are
      performed to study the performance of the proposed method. For illustration
      purpose, the method is applied to a breast cancer data set from the public domain
      to investigate the effect of onset age on the disease-free survival of the
      patients. The results revealed that the risk is highest among young patients and
      young postmenopausal patients, probably because of a change in hormonal
      environment during a certain phase of menopause.

PMID- 29468717
TI  - Brysocarpus coccineus (Schum & Thonn) root reinstates sexual competence and
      testicular function in paroxetine-induced sexual dysfunction in male Wistar rats.
AB  - The effects of aqueous extract of Brysocarpus coccineus roots (AEBCR) were
      studied on sexual behaviour and testicular function of paroxetine-induced sexual
      dysfunction (SD) in male rats. Ninety, sexually matured male rats (150.88 +/-
      5.53 g) were assigned into two groups: A and B. Fifteen SD animals from group B
      were each allotted to B1, B2, B3, B4 and B5 and received distilled water (DW),
      Powmax M (7.14 mg/kg body weight, b.w.) 50, 100 and 150 mg/kg b.w of AEBCR,
      respectively, for 7 days while the non-SD animals (group A) received DW. Eleven
      secondary metabolites were present in AEBCR. The lowered (p < .05) ejaculation
      frequency, penile erection index and penile grooming, higher mount and
      intromission frequencies, prolonged (p < .05) latencies of mount, intromission,
      ejaculation, and post-ejaculatory interval, reduced (p < .05) serum luteinising
      hormone, follicle stimulating hormone, testosterone, nitric oxide and testicular
      function indices, degenerated seminiferous tubules and low luminal spermatozoa
      contents by paroxetine were significantly (p < .05) attenuated and/or reinstated
      by AEBCR and Powmax M. The restoration of androgen-dependent sexual and
      testicular functions in SD male rats by AEBCR validates its folkloric use as
      aphrodisiac. Clinical studies are desirable to ascertain the efficacy of AEBCR in
      SD.

PMID- 29468718
TI  - Nurses' turnover intention: The impact of leader-member exchange, organizational
      identification and job embeddedness.
AB  - AIM: The aim of this study was to examine the influence of three factors on
      turnover intention: leader-member exchange quality, organizational identification
      and job embeddedness. This area of inquiry has not been fully investigated in the
      literature. BACKGROUND: Employee turnover, particularly of professionals, becomes
      a very challenging issue. It continually affects organizations in terms of
      resourcing and developmental costs, manpower instability, day-to-day operations,
      perception of quality care and efficiency. Therefore, employees' working attitude
      and behaviour have drawn increasing attention for further research to determine
      which factors keep them with their employer. DESIGN: A cross-sectional survey was
      conducted with self-report questionnaires. METHODS: Data were collected from
      1,966 nurses from sixteen private general hospitals in Thailand during February
      June 2016. Hypotheses were tested and analysed by means of a confirmatory factor
      analysis, structural equation modelling and a bootstrapping procedure. RESULTS:
      The results revealed the direct relationship between leader-member exchange
      quality and job embeddedness. Organizational identification played an
      intermediary role that partially mediated the relationship between leader-member
      exchange quality on job embeddedness. Analysis also provided support for the
      mediating effect of organizational identification and turnover intention through
      job embeddedness. CONCLUSION: This study extends the job embeddedness theory and
      gains understanding of the antecedent factors that directly and indirectly cause
      employees to become embedded and lead to predict turnover intention. The findings
      are pertinent, as few studies have investigated such relationships. The
      implications provide insights into how organizations can better retain their
      workforce.

PMID- 29468719
TI  - Assessing health facility performance in Indonesia using the Pabon-Lasso model
      and unit cost analysis of health services.
AB  - Total health care costs have dramatically increased in Indonesia, and health
      facilities consume the largest share of health resources. This study aims to
      provide a better understanding of the characteristics of the best-performing
      health facilities. We use 4 national Indonesian datasets for 2011 and analysed
      200 hospitals and 95 health centres. We first apply the Pabon-Lasso model to
      assess the relative performance of health facilities in terms of bed occupancy
      rate and the number of admissions per bed; the model gathers together health
      facilities into 4 sectors representing different levels of productivity. We then
      use a step-down costing method to estimate the cost per outpatient visit,
      inpatient, and bed days in hospitals and health centres. We combined both ratio
      analysis and applied bivariate and multivariate analyses to identify the
      predictors of the best-performing health facility; 37% of hospitals and 33% of
      health centres were located in the high-performing sector of the Pabon-Lasso
      model. The wide variation in unit costs across health facilities presented a
      basis for benchmarking and identifying relatively efficient units. Combining the
      unit cost analysis and Pabon-Lasso model, we find that health facility
      performance is affected by both internal (size and capacity, financing, type of
      patients, ownership, accreditation status, and staff availability) and external
      factors (economic status, population education level, location, and population
      density). Our study demonstrates that it is feasible to identify the best
      performing health facilities and provides information about how to improve
      efficiency using simplistic methods.

PMID- 29468720
TI  - Family management of childhood atopic dermatitis.
AB  - AIMS: To identify the variables that affect family management of childhood atopic
      dermatitis and establish a prediction model based on Bandura's self-efficacy
      theory. BACKGROUND: Atopic dermatitis is a chronic recurrent skin disease and
      common health problem in childhood. It is necessary to use an approach that
      includes parental factors when considering the effective management of childhood
      atopic dermatitis. DESIGN: A cross-sectional study design. METHODS: A convenience
      sample, comprising 168 Korean mothers caring for a child with atopic dermatitis
      under the age of 13, was recruited from the paediatric outpatient departments of
      two general hospitals in Seoul, South Korea. Data were collected using structured
      self-reported questionnaires including severity, antecedents, effort, self
      efficacy and family management of childhood atopic dermatitis from 1 November
      2015-28 February 2016. Descriptive statistics about the participants and
      variables were examined and data were analysed using structural equation
      modelling. RESULTS: The hypothetical model had an adequate fit to the data,
      indicating that severity, antecedents, effort and self-efficacy influenced family
      management of childhood atopic dermatitis. CONCLUSION: These results suggest that
      strategies to support children with atopic dermatitis and their family should
      consider the influence of such variables.

PMID- 29468721
TI  - Measurements and simulation of RF heating of implanted stereo
      electroencephalography electrodes during MR scans.
AB  - PURPOSE: To assess RF-induced heating during MRI of patients with implanted
      stereo-electroencephalography electrodes. METHODS: Simulations and experimental
      measurements using phantom and a head-only transmit/receive coil on a 3T MR
      system were performed to evaluate temperature increases at the tip of an 8
      contact stereo-electroencephalography electrode and an insulated wire partially
      immersed into the phantom. The lengths of wire producing maximum (resonant
      condition) and minimum (anti-resonant condition) heating were evaluated for
      different entry modes and penetration depths. RESULTS: For both wire and stereo
      electroencephalography electrode, resonant lengths were close to odd integral
      multiples of RF quarter wavelength in air and antiresonant length close to even
      integral multiples of RF quarter wavelength, both being unaffected by the entry
      mode. In the resonant condition, temperature increased by as much as a factor of
      10 higher than that at antiresonant condition. Larger penetration depths did not
      change resonant length, but did lead to increased RF heating. CONCLUSION: For the
      partially immersed implants like stereo-electroencephalography electrode, the
      resonant lengths were found to be independent of the penetration depths and entry
      modes, although the temperature increases may vary. Avoiding such lengths of
      cables can reduce the risk of tissue heating during in vivo MRI.

PMID- 29468722
TI  - Podoplanin-positive myofibroblasts: a pathological hallmark of pleuroparenchymal
      fibroelastosis.
AB  - Pathological differential diagnoses of pleuroparenchymal fibroelastosis (PPFE)
      include usual interstitial pneumonia (UIP) and pulmonary apical cap (PAC);
      however, there are no specific immunostaining makers to distinguish between these
      diseases. We performed immunohistochemistry using several pleural mesothelial
      cell-related markers, including cytokeratin-5/6, CAM5.2, WT-1, calretinin, desmin
      and podoplanin, for PPFE (n = 4), UIP (n = 10) and PAC (n = 3) lung sections.
      Among the examined markers, in PPFE and PAC lungs podoplanin commonly showed
      positivity for spindle cells both in thickened pleura and subpleural
      fibroelastosis lesions; these cells were also stained with alpha-smooth muscle
      actin, a marker of myofibroblasts. However, even in elastic fibre-rich cases, UIP
      lungs did not show such podoplanin-positive myofibroblasts in pleura/subpleura
      and fibroblastic foci. These findings were also verified using
      immunofluorescence. By contrast, immunohistochemically as well as
      morphologically, the difference between PPFE and PAC was not apparent. The
      presence of podoplanin-positive myofibroblasts could be a pathological hallmark
      of PPFE, suggesting a pathogenic process distinct from UIP but common to PAC.

PMID- 29468723
TI  - Bayesian nonparametric inference for panel count data with an informative
      observation process.
AB  - In this paper, the panel count data analysis for recurrent events is considered.
      Such analysis is useful for studying tumor or infection recurrences in both
      clinical trial and observational studies. A bivariate Gaussian Cox process model
      is proposed to jointly model the observation process and the recurrent event
      process. Bayesian nonparametric inference is proposed for simultaneously
      estimating regression parameters, bivariate frailty effects, and baseline
      intensity functions. Inference is done through Markov chain Monte Carlo, with
      fully developed computational techniques. Predictive inference is also discussed
      under the Bayesian setting. The proposed method is shown to be efficient via
      simulation studies. A clinical trial dataset on skin cancer patients is analyzed
      to illustrate the proposed approach.

PMID- 29468724
TI  - A roadmap to advance dementia research in prevention, diagnosis, intervention,
      and care by 2025.
AB  - OBJECTIVE: National and global dementia plans have focused on the research
      ambition to develop a cure or disease-modifying therapy by 2025, with the initial
      focus on investment in drug discovery approaches. We set out to develop
      complementary research ambitions in the areas of prevention, diagnosis,
      intervention, and care and strategies for achieving them. METHODS: Alzheimer's
      Society facilitated a taskforce of leading UK clinicians and researchers in
      dementia, UK funders of dementia research, people with dementia, and carer
      representatives to develop, using iterative consensus methodology, goals and
      recommendations to advance dementia research. RESULTS: The taskforce developed 5
      goals and 30 recommendations. The goals focused on preventing future cases of
      dementia through risk reduction, maximising the benefit of a dementia diagnosis,
      improving quality of life, enabling the dementia workforce to improve practice,
      and optimising the quality and inclusivity of health and social care systems.
      Recommendations addressed gaps in knowledge and limitations in research
      methodology or infrastructure that would facilitate research in prioritised
      areas. A 10-point action plan provides strategies for delivering the proposed
      research agenda. CONCLUSIONS: By creating complementary goals for research that
      mirror the need to find effective treatments, we provide a framework that enables
      a focus for new investment and initiatives. This will support a broader and more
      holistic approach to research on dementia, addressing prevention, surveillance of
      population changes in risk and expression of dementia, the diagnostic process,
      diagnosis itself, interventions, social support, and care for people with
      dementia and their families.

PMID- 29468725
TI  - A clinical risk score to identify patients at high risk of very late stent
      thrombosis.
AB  - OBJECTIVES: The aim of this study was to determine predictors of very late stent
      thrombosis (VLST; >1 year after stenting), and to evaluate whether addition of
      these predictors to the dual antiplatelet therapy (DAPT) score would improve the
      ability to identify patients at high risk of VLST who might benefit from DAPT.
      BACKGROUND: VLST is a severe complication of percutaneous coronary intervention
      (PCI). Extended knowledge about the predictors of VLST is needed to prevent this
      life-threatening complication. Recent data showed a reduction in VLST after
      treatment with prolonged DAPT. The DAPT study developed a prediction score to
      identify patients after PCI who might benefit from prolonged DAPT duration.
      METHODS: The Dutch stent thrombosis study is a multi-center case-control study.
      Consecutive patients with definite VLST were included between 2007 and 2014.
      Baseline characteristics from the index PCI were collected. Independent
      predictors of VLST were identified and added to the DAPT score to develop the
      VLST score. RESULTS: In total, 155 VLST cases and 155 matched controls were
      included. Suboptimal result of stenting, right coronary artery as target vessel,
      and diffuse coronary artery ectasia were independent predictors of VLST, and
      added to the DAPT score. The power of the VLST score to identify patients who
      experienced VLST was increased (AUC, 95%CI; DAPT score: 0.64, 0.57-0.70; VLST
      score: 0.70, 0.63-0.76, P = 0.010). CONCLUSIONS: Addition of newly identified
      independent predictors of VLST resulted in a prediction model with a higher
      ability to identify patients at high risk of VLST who might benefit from
      prolonged DAPT.

PMID- 29468726
TI  - Immunohistochemical expression of CD44 in oral squamous cell carcinoma in
      relation to histomorphological parameters and clinicopathological factors.
AB  - AIMS: Oral squamous cell carcinoma (OSCC) is characterised by its variable
      clinical course. In addition to the routinely used TNM and Union for
      International Cancer Control systems, patient-specific prognostic/predictive
      biomarkers are needed. Promising biomarkers include the determination of the
      cancer stem cell compartment, which can be identified by CD44 expression (among
      other things). The aim of this study was to evaluate the impact of CD44 in OSCC
      in terms of correlation with histomorphology, especially targeting features of
      EMT, and its influence on patient prognosis. METHODS AND RESULTS: A well
      characterised cohort of 108 therapy-naive OSCCs with complete long-term follow-up
      and matched lymph node metastases were evaluated for CD44 expression by
      immunohistochemistry. CD44 expression was correlated with histomorphological
      characteristics (including tumour differentiation and tumour budding),
      clinicopathological parameters, and follow-up data. Overexpression of CD44 was
      detected in 37% of OSCCs within the tumour centre, in 39% of OSCCs at the
      invasive margin, and in 16% of lymph node metastases. CD44 overexpression at the
      invasive margin was significantly correlated with poor histopathological
      differentiation, and specifically with high tumour budding activity and single
      cell invasion as signs of epithelial-mesenchymal transition (EMT). CD44
      overexpression within the tumour core region and in lymph node metastases was
      identified as an independent prognostic factor for poor overall, disease-specific
      and disease-free survival in subsets of patients with advanced OSCC. CONCLUSION:
      Our study demonstrates the association of CD44 with tumour aggressiveness and
      EMT, as well as the independent prognostic impact of CD44 in a subset of OSCCs,
      which underlines the role of tumour cell stemness as a key factor in malignant
      behaviour in this disease.

PMID- 29468727
TI  - Simultaneous multislice triple-echo steady-state (SMS-TESS) T1 , T2 , PD, and off
      resonance mapping in the human brain.
AB  - PURPOSE: To investigate the ability of simultaneous multislice triple-echo steady
      state (SMS-TESS) imaging to provide quantitative maps of multiple tissue
      parameters, i.e., longitudinal and transverse relaxation times (T1 and T2 ),
      proton density (PD), and off-resonance (DeltaB0 ), in the human brain at 3T from
      a single scan. METHODS: TESS acquisitions were performed in 2D mode to reduce
      motion sensitivity and accelerated by an SMS excitation scheme (CAIPIRINHA) with
      SENSE reconstruction. SMS-acceleration factors (R) of 2 and 4 were evaluated. The
      in vitro and in vivo validation process included standard reference scans to
      analyze the accuracy of T1 , T2 , and DeltaB0 estimates, as well as single-slice
      TESS measurements. RESULTS: For R = 2, the quantification of T1 , T2 , PD, and
      DeltaB0 was overall reliable with marginal noise enhancement. T1 and T2 values
      were in good agreement with the reference measurements and single-slice TESS. For
      R = 4, the agreement of DeltaB0 with the standard reference was excellent and the
      determination of T1 , T2 , and PD was reproducible; however, increased variations
      in T1 and T2 values with respect to single-slice TESS were observed. CONCLUSION:
      SMS-TESS has shown potential to offer rapid simultaneous T1 , T2 , PD, and
      DeltaB0 mapping of human brain tissues.

PMID- 29468729
TI  - Literature overview highlights lack of paediatric donation protocols but
      identifies common themes that could guide their development.
AB  - AIM: Paediatric donation is a unique and extremely sensitive process that
      requires specific knowledge and competencies. Most countries use protocols for
      organ and tissue donation to ensure optimal care for the donor and family, but
      these mainly focus on adults. However, the donation process for children differs
      from adults in many ways. An overview of the literature was performed to identify
      protocols for the paediatric population. METHODS: PubMed, Web of Science, EMBASE
      and the Internet were searched up to March 2016 for papers or other sources in
      English related to specific organ and tissue donation protocols for children and
      neonates. This comprised title, abstract and then full-text screening of relevant
      data. RESULTS: We included 12 papers and two electronic sources that were mainly
      from North America and Europe. Most discussed donations after cardiac death. The
      recurring themes included identifying potential donors, approaching parents,
      palliative care and collaboration with organ procurement organisations. Most
      papers called for paediatric donation policies to be standardised. CONCLUSION:
      Scientific publications in English on paediatric donation protocols are very
      scarce. No comprehensive paediatric donation protocol was found. We identified
      several recurring themes in the literature that could be used to develop such
      protocols.

PMID- 29468728
TI  - European Surveillance System on Contact Allergies (ESSCA): polysensitization,
      2009-2014.
AB  - BACKGROUND: Polysensitization, defined as being allergic to three or more haptens
      from the European baseline series, is considered to reflect increased
      susceptibility to developing a contact allergy, and is likely to be associated
      with an impaired quality of life. OBJECTIVES: To evaluate the prevalences of
      polysensitization across Europe and to analyse factors associated with
      polysensitization. METHODS: Patch test data collected by the European
      Surveillance System on Contact Allergies (ESSCA; www.essca-dc.org) in
      consecutively patch tested patients from January 2009 to December 2014,
      comprising 11 countries and 57 departments, were retrospectively analysed.
      RESULTS: A total of 86 416 patients were available for analysis, showing a
      standardized prevalence of polysensitization of 7.02%, ranging from 12.7%
      (Austria) to 4.6% (Italy). Allergen pairs with the strongest association are
      reported for the total population, for South Europe, and for North/Central
      Europe. Overall, polysensitized patients showed a higher percentage of extreme
      (+++) positive patch test reactions than oligosensitized patients. Female sex,
      occupational dermatitis and age > 40 years were risk factors for
      polysensitization. CONCLUSIONS: The varying prevalences of polysensitization
      across Europe most likely reflect differences in patient characteristics and
      referral patterns between departments. Known risk factors for polysensitization
      are confirmed in a European dermatitis population.

PMID- 29468730
TI  - Comparison of three treatment strategies for patients with triple-vessel coronary
      disease and left ventricular dysfunction.
AB  - INTRODUCTION: Current guidelines recommend coronary artery bypass grafting (CABG)
      for patients with multivessel coronary disease and left ventricular (LV)
      dysfunction. However, some patients undergo percutaneous coronary intervention
      (PCI) or solely medical therapy (MT) in actual practice. The comparison of long
      term outcomes of these three treatment strategies in real world is unclear.
      METHODS: A total of 699 consecutive patients in a single centre from 2004 to 2011
      who had TVD and LV ejection fraction <=40%, no prior PCI or CABG and had
      completed a median 6.2-year follow-up were evaluated. The primary endpoint was
      all-cause death. The secondary endpoints included cardiac death, major adverse
      cardiovascular and cerebrovascular events (MACCE; composite of all-cause death,
      myocardial infarction, repeat revascularization, or stroke), and the individual
      components of the composite endpoint. RESULTS: One hundred forty-two patients
      (20.3%) underwent PCI, 201 (28.8%) underwent CABG while 356 (50.9%) received MT
      alone. MT alone was associated with the worst survival (P < 0.001). Compared with
      PCI, CABG was associated with a similar risk of all-cause death (hazard ratio
      [HR], 0.86; 95% confidence interval [CI], 0.52-1.41; P = 0.54) but lower risks of
      cardiac death (HR, 0.47; 95%CI, 0.25-0.91; P = 0.03), repeat revascularization
      (HR, 0.29; 95%CI, 0.10-0.85; P = 0.02), and MACCE (HR, 0.63; 95%CI, 0.43-0.93; P
      = 0.02). CONCLUSIONS: For patients with TVD and LV dysfunction, both CABG and PCI
      were associated with a lower risk of mortality compared with MT alone. Compared
      with PCI, CABG has a lower risk of cardiac death, repeat revascularization, and
      MACCE.

PMID- 29468733
TI  - Reciprocal leadership in clinical supervision comes of age.

PMID- 29468732
TI  - Antidepressant effects of dammarane sapogenins in chronic unpredictable mild
      stress-induced depressive mice.
AB  - Depression is a common, dysthymic, and psychiatric disorder, resulting in
      enormous social and economic burden. Dammarane sapogenins (DS), an active
      fraction from oriental ginseng, has shown antidepressant-like effects in chronic
      restraint rats and sleep interruption-induced mice, and the present study aimed
      to further confirm the antidepressant effects of DS in a model of chronic
      unpredictable mild stress (CUMS) and to explore the underlying mechanism. Oral
      administration of DS (20, 40, and 80 mg/kg) markedly improved depressant-like
      behaviors, increasing the sucrose intake in the sucrose preference test and
      reducing the latency in the novelty-suppressed feeding test, and decreasing the
      immobility time in both the tail suspension and forced swimming tests, compared
      with the CUMS mice. Biochemical analysis of brain tissue and serum showed that DS
      treatment restored the decreased hippocampal neurotransmitter concentrations of
      serotonin, dopamine, norepinephrine (noradrenaline), and gamma-aminobutyric acid,
      and decreased the elevated of serum hormone levels (corticotrophin releasing
      factor, adrenocorticotrophic hormone, and corticosterone) induced by CUMS. Our
      findings confirm that DS exerts an antidepressant-like effect in the CUMS model
      of depression in mice, and suggest it may be mediated by regulation of
      neurotransmitters and hypothalamic-pituitary-adrenal axis.

PMID- 29468731
TI  - Nutritional influences on brain development.
AB  - : There is increasing evidence from preclinical and human studies that nutrition
      in the late foetal and early neonatal period has a significant impact on
      neurodevelopment across the lifespan. Certain nutrients have particularly large
      effects in this time period, and their deficits cause greater long-term risk. The
      mechanisms by which nutrients influence early brain growth and the sensitive
      periods for when certain nutrients should be provided are being elucidated.
      Assessments of nutritional status that index brain growth and predict long-term
      development are important to assess the efficacy of early life nutritional
      therapies. CONCLUSION: Optimizing nutrition during foetal and early postnatal
      life is a golden opportunity to impact neurodevelopment and brain function across
      the lifespan.

PMID- 29468734
TI  - In patients undergoing percutaneous coronary intervention with rotational
      atherectomy radial access is safer and as efficient as femoral access.
AB  - INTRODUCTION: Transfemoral approach (TFA) may be preferred access site in order
      to facilitate complex percutaneous procedures such as rotational atherectomy
      (RA). Notwithstanding, there is a growing evidence that transradial approach
      (TRA) is associated with lower access site complication rates and even lower
      mortality. The aim was to assess in-hospital and 1-year outcomes in patients
      undergoing RA using TRA, in comparison to TFA. METHODS: A single center
      observational study included all consecutive patients, who underwent RA from 2010
      to 2015. Primary endpoints were procedural success, in-hospital mortality and
      major adverse cardiovascular events (MACE). Secondary endpoints were 1-year all
      cause mortality and MACE. RESULTS: The study included 177 patients, 69% in TRA
      group and 31% in TFA group. Except for male sex and logistic Euroscore II there
      were no differences in common risk factors. There was no difference in procedural
      success (95% vs 87%, P = 0.07) with even a trend in favor of TRA. Performing RA
      via TRA lower amount of contrast volume (P = 0.009) was used and hospital stay
      after the procedure was shorter (P = 0.004). Periprocedural complication rates
      were similar, however patients with TFA had significantly higher rate of major
      access site bleedings (13% vs 1%, P = 0.001), with no differences in mortality
      and other adverse events both in-hospital and during 1-year observation.
      CONCLUSIONS: Even though RA is a demanding technique, when performed via TRA
      allows to maintain the same procedural success and long-term results in
      comparison to TFA, reduces in-hospital major access site bleedings, lowers the
      amount of contrast media and shortens hospital stay.

PMID- 29468735
TI  - Characterization and Manipulation of Spin Orbit Torque in Magnetic
      Heterostructures.
AB  - Electrical-current-induced magnetization switching is a keystone concept in the
      development of spintronics devices. In the last few years, this field has
      experienced a significant boost with the discovery of spin orbit torque (SOT) in
      magnetic heterostructures. Here, the recent results as to the characterization
      and manipulation of SOT in various heavy-metal/ferromagnet heterostructures are
      summarized. First, different electrical measurement methods that allow the
      physical features of SOT to be revealed are introduced. Second, it is shown that
      SOT in magnetic heterostructures can be manipulated via various material
      engineering approaches. The interfacial and bulk contributions of SOT are also
      discussed. These results advance the understanding of SOT and provide novel
      approaches toward energy-efficient spintronic devices.

PMID- 29468736
TI  - Bioinspired Wood Nanotechnology for Functional Materials.
AB  - It is a challenging task to realize the vision of hierarchically structured
      nanomaterials for large-scale applications. Herein, the biomaterial wood as a
      large-scale biotemplate for functionalization at multiple scales is discussed, to
      provide an increased property range to this renewable and CO2 -storing
      bioresource, which is available at low cost and in large quantities. The Progress
      Report reviews the emerging field of functional wood materials in view of the
      specific features of the structural template and novel nanotechnological
      approaches for the development of wood-polymer composites and wood-mineral
      hybrids for advanced property profiles and new functions.

PMID- 29468738
TI  - Combined effects of environmental factors on human perception and objective
      performance: A review of experimental laboratory works.
AB  - This study reports the outcomes of a literature survey aimed at exploring how
      different environmental factors-that is acoustic, thermal, visual, and air
      quality stimuli-interact in affecting building occupants' perception and
      performance. Recent laboratory studies have been collected, and their
      methodological approaches reviewed in terms of experimental design, adopted
      exposures conditions, perception and performance assessment methods. Results have
      been summarized and compared to identify interaction patterns between
      environmental factors and possible practical implications for improving the
      design of both experimental studies and the built environment. The analysis
      allows highlighting limitations, potential improvements and future opportunities
      in this field of research, thus providing a reference for further investigations
      aimed at a deeper understanding, modeling, and prediction of the impacts caused
      by the main indoor variables on human comfort and performance.

PMID- 29468737
TI  - School-based study found that physical activity and aerobic fitness predicted
      increases in total body fat and abdominal fat at a mean age of 9.8 years.
AB  - AIM: We assessed whether baseline measurements of physical activity, aerobic
      fitness, body fat and abdominal fat were predictors of changes in body fat
      measurements over a two-year period. METHODS: The study comprised of 204 children
      aged 9.8 +/- 0.6 years with a normal body mass distribution, who recruited from
      four schools in middle-class areas of Malmo, Sweden, from 2001 to 2004. Peak
      oxygen uptake and physical activity were measured at baseline. Body fat was
      measured by dual-energy X-ray absorptiometry at baseline and two years later.
      RESULTS: Physical activity, aerobic fitness and total body fat or abdominal fat
      were predictors of change in total body fat or abdominal fat over a period of two
      years. Changes in the percentage of body fat were not related to any of the
      baseline measurements. CONCLUSION: Our two-year follow-up of children with a mean
      age of 9.8 years at baseline showed that physical activity, aerobic fitness and
      body fat or abdominal fat predicted changes in total body fat or abdominal fat,
      but not the percentage of body fat.

PMID- 29468739
TI  - Armed conflict, health spending, and HIV.
AB  - Among current studies, there is still question as to whether conflict increases,
      decreases, or has no effect on HIV prevalence. This lack of clarity can be
      attributed to the scarcity of quantitative analysis in this field. Thus, studies
      about conflict and HIV have failed to specify the ways conflict affects HIV
      prevalence, if indeed it does. In this paper, I argue that armed conflict
      increases HIV prevalence by reducing total per capita health spending. Using HIV
      prevalence data from 1990 to 2009, I find supporting evidence in the case of
      civil conflicts for these arguments. In addition, I find that as the severity of
      civil conflict increases, so do HIV rates. These findings have significant policy
      implications for individual governments, as well as for the international
      community.

PMID- 29468740
TI  - Neuroprotective effects of 20(S)-protopanaxatriol (PPT) on scopolamine-induced
      cognitive deficits in mice.
AB  - 20(S)-protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has
      been reported to have neuroprotective effects and to improve memory. The present
      study was designed to investigate the protective effect of PPT on scopolamine
      induced cognitive deficits in mice. Male Institute of Cancer Research mice were
      pretreated with 2 different doses of PPT (20 and 40 MUmol/kg) for 27 days by
      intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected
      intraperitoneally for 9 days to induce memory impairment. Thirty minutes after
      the last pretreatment, the locomotor activity was firstly examined to evaluate
      the motor function of mice. Then, memory-related behaviors were evaluated, and
      the related mechanism was further researched. It was founded that PPT treatment
      significantly reversed scopolamine-induced cognitive impairment in the object
      location recognition experiment, the Morris water maze test, and the passive
      avoidance task, showing memory-improving effects. PPT also significantly improved
      cholinergic system reactivity and suppressed oxidative stress, indicated by
      inhibition of acetylcholinesterase activity, elevation of acetylcholine levels,
      increasing superoxide dismutase activity and lowering levels of malondialdehyde
      in the hippocampus. In addition, the expression levels of Egr-1, c-Jun, and cAMP
      responsive element binding in the hippocampus were significantly elevated by PPT
      administration. These results suggest that PPT may be a potential drug candidate
      for the treatment of cognitive deficit in Alzheimer's disease.

PMID- 29468741
TI  - Age-dependent skin texture analysis and evaluation using mobile camera image.
AB  - BACKGROUND/PURPOSE: The aim of this study was to evaluate skin condition,
      expensive equipment is required, continuous skin care is difficult. Therefore, we
      obtain the skin image using mobile camera, and propose a new algorithm that
      easily and simply extracts skin features. METHODS: We analyze skin features,
      extracting the wrinkle length, cell area, and the number of cells. To get
      accurate skin features, we obtain a new skin binary image, and apply Watershed
      segmentation to it. So, we improve the accuracy of skin analysis. Therefore, we
      compare and analyze the degree of matching distribution of wrinkles, the shape of
      the cell, etc., using similarity between the ground truth and the proposed
      algorithm result image. RESULTS: We extract skin surface features using a mobile
      camera image, and verify the change in skin features with age. Also, we
      demonstrate the superiority of the proposed algorithm through the similarity
      between the ground truth and proposed result image. CONCLUSION: The proposed
      method in this study shows that the skin surface can be quantitatively evaluated
      by the similarity with ground truth. We also propose a method to diagnose and
      manage individual skin condition using a mobile camera in real life.

PMID- 29468742
TI  - Dog introduction alters the home dust microbiota.
AB  - Research has largely reported that dog exposure is associated with reduced
      allergic disease risk. Responsible mechanism(s) are not understood. The goal was
      to investigate whether introducing a dog into the home changes the home dust
      microbiota. Families without dogs or cats planning to adopt a dog and those who
      were not were recruited. Dust samples were collected from the homes at
      recruitment and 12 months later. Microbiota composition and taxa (V4 region of
      the 16S rRNA gene) were compared between homes that did and did not adopt a dog.
      A total of 91 dust samples from 54 families (27 each, dog and no dog; 17 dog and
      20 no dog homes with paired samples) were analyzed. A significant dog effect was
      seen across time in both unweighted UniFrac and Canberra metrics (both P = .008),
      indicating dog introduction may result in rapid establishment of rarer and
      phylogenetically related taxa. A significant dog-time interaction was seen in
      both weighted UniFrac (P < .001) and Bray-Curtis (P = .002) metrics, suggesting
      that while there may not initially be large relative abundance shifts following
      dog introduction, differences can be seen within a year. Therefore, dog
      introduction into the home has both immediate effects and effects that emerge
      over time.

PMID- 29468743
TI  - A phytomodulatory hydrogel with enhanced healing effects.
AB  - The healing performance of a hydrogel composed of hemicelluloses extracted from
      seeds of Caesalpinia pulcherrima (Fabaceae) and mixed with phytomodulatory
      proteins obtained from the latex of Calotropis procera was characterized on
      excisional wounds. The hydrogel did not induce dermal irritability. When
      topically used on excisional wounds, the hydrogel enhanced healing by wound
      contraction. Histology and the measurement of inflammatory mediators
      (myeloperoxidase, interleukin-1beta, and interleukin-6) suggested that the
      inflammatory phase of the healing process was intensified, stimulating
      fibroplasia and neovascularization (proliferative phase) and tissue remodeling by
      increasing new collagen fiber deposition. In addition, reduction on levels of
      malondialdehyde in the groups that the hydrogel was applied suggested that the
      oxidative stress was reduced. The hydrogel performed better than the reference
      drug used, as revealed by the extended thickness of the remodeled epithelium.

PMID- 29468744
TI  - Cytotoxic alkaloids from Pogonopus tubulosus: G2/M cell cycle arrest and
      inhibition of DNA topoisomerase IIalpha by isotubulosine.

PMID- 29468745
TI  - Promises, Challenges, and Recent Progress of Inorganic Solid-State Electrolytes
      for All-Solid-State Lithium Batteries.
AB  - All-solid-state lithium batteries (ASSLBs) have the potential to revolutionize
      battery systems for electric vehicles due to their benefits in safety, energy
      density, packaging, and operable temperature range. As the key component in
      ASSLBs, inorganic lithium-ion-based solid-state electrolytes (SSEs) have
      attracted great interest, and advances in SSEs are vital to deliver the promise
      of ASSLBs. Herein, a survey of emerging SSEs is presented, and ion-transport
      mechanisms are briefly discussed. Techniques for increasing the ionic
      conductivity of SSEs, including substitution and mechanical strain treatment, are
      highlighted. Recent advances in various classes of SSEs enabled by different
      preparation methods are described. Then, the issues of chemical stabilities,
      electrochemical compatibility, and the interfaces between electrodes and SSEs are
      focused on. A variety of research addressing these issues is outlined
      accordingly. Given their importance for next-generation battery systems and
      transportation style, a perspective on the current challenges and opportunities
      is provided, and suggestions for future research directions for SSEs and ASSLBs
      are suggested.

PMID- 29468746
TI  - Surveillance for azoles resistance in Aspergillus spp. highlights a high number
      of amphotericin B-resistant isolates.
AB  - Aspergillus spp. are the most common invasive mould infection and are responsible
      for high mortality. Aspergillus fumigatus is currently of interest because
      resistance to azole antifungals has emerged. The Campinas University Hospital (HC
      UNICAMP) receives high-risk patients susceptible to opportunistic infections but
      there have been no reports of resistant A. fumigatus. This study aimed to assess
      the susceptibility profile of Aspergillus isolates, specifically looking for
      azole resistance. ITS and beta-tubulin DNA sequencing was performed on 228
      sequential clinical isolates. Broth microdilution susceptibility testing was
      performed for all isolates. A. fumigatus represented 74% of the isolates followed
      by Aspergillus flavus (12%). Nine A. fumigatus isolates from 9 different patients
      showed high MIC values to at least 1 azole, but cyp51A polymorphisms were
      detected in only 6 isolates and none correlated with known resistance mutations.
      The most troubling observation was that the minimum inhibitory concentration for
      amphotericin B was elevated (>=2 mg L-1 ) in 87% of patients with A. flavus
      isolates and 43% with Aspergillus fumigatus isolates. Given that amphotericin B
      is used to treat azole-resistant infections, these data highlight the need for
      continuous surveillance in Aspergillus for all antifungal resistance to implement
      correct treatment strategies for the management of these pathogens.

PMID- 29468747
TI  - Biocompatible Semiconductor Quantum Dots as Cancer Imaging Agents.
AB  - Approximately 1.7 million new cases of cancer will be diagnosed this year in the
      United States leading to 600 000 deaths. Patient survival rates are highly
      correlated with the stage of cancer diagnosis, with localized and regional
      remission rates that are much higher than for metastatic cancer. The current
      standard of care for many solid tumors includes imaging and biopsy with
      histological assessment. In many cases, after tomographical imaging modalities
      have identified abnormal morphology consistent with cancer, surgery is performed
      to remove the primary tumor and evaluate the surrounding lymph nodes. Accurate
      identification of tumor margins and staging are critical for selecting optimal
      treatments to minimize recurrence. Visible, fluorescent, and radiolabeled small
      molecules have been used as contrast agents to improve detection during real-time
      intraoperative imaging. Unfortunately, current dyes lack the tissue specificity,
      stability, and signal penetration needed for optimal performance. Quantum dots
      (QDs) represent an exciting class of fluorescent probes for optical imaging with
      tunable optical properties, high stability, and the ability to target tumors or
      lymph nodes based on surface functionalization. Here, state-of-the-art
      biocompatible QDs are compared with current Food and Drug Administration approved
      fluorophores used in cancer imaging and a perspective on the pathway to clinical
      translation is provided.

PMID- 29468748
TI  - The effect of dietary soy intake on weight loss, glycaemic control, lipid
      profiles and biomarkers of inflammation and oxidative stress in women with
      polycystic ovary syndrome: a randomised clinical trial.
AB  - BACKGROUND: The present study aimed to evaluate the effects of dietary soy intake
      on weight loss and metabolic status of patients with polycystic ovary syndrome
      (PCOS). METHODS: A randomised clinical trial was conducted among 60 women with
      PCOS. Participants were randomly assigned into two groups to receive either a
      test diet (n = 30) or a control diet (n = 30) for 8 weeks. Participants in the
      test group consumed a diet containing 0.8 g protein kg-1 body weight (35% animal
      proteins, 35% soy protein and 30% vegetable proteins) and participants in the
      control group consumed a similar diet containing 70% animal proteins and 30%
      vegetable proteins. RESULTS: Adherence to the test diet, compared with the
      control diet, resulted in significant decreases [mean (SD)] in body mass index
      (BMI) [-0.3 (0.6) versus +0.1 (0.5) kg m-2 , P = 0.02], fasting plasma glucose [
      0.2 (0.5) versus +0.1 (0.3) mmol L-1 , P = 0.01], total testosterone [-0.3 (0.7)
      versus +0.3 (0.3) mmol L-1 , P < 0.001], insulin [-15.0 (18.0) versus +4.8 (18.6)
      pmol L-1 , P < 0.001] and insulin resistance [-0.6 (0.6) versus +0.2 (0.7), P <
      0.001], as well as a significant increase in quantitative insulin sensitivity
      check index [+0.01 (0.01) versus -0.002 (0.02), P = 0.01]. In addition,
      significant decreases in triglycerides [-0.1 (0.4) versus +0.2 (0.3) mmol L-1 , P
      = 0.01] and malondialdehyde (MDA) [-1.2 (1.0) versus +0.2 (1.2) MUmol L-1 , P <
      0.001] and significant increases in nitric oxide (NO) [+13.6 (14.1) versus +0.9
      (24.3) MUmol L-1 , P = 0.01] and glutathione (GSH) [+170.1 (175.5) versus +24.2
      (168.7) MUmol L-1 , P = 0.002] were seen in the test group compared to the
      control. CONCLUSIONS: Adherence to test diet among subjects with PCOS
      significantly decreased BMI, glycaemic control, total testosterone, triglycerides
      and MDA, and significantly increased NO and GSH compared to the control diet.

PMID- 29468749
TI  - The effect of pre-pregnancy lifestyle counselling on food intakes and association
      between food intakes and gestational diabetes in high-risk women: results from a
      randomised controlled trial.
AB  - BACKGROUND: Healthy diets before and during pregnancy have been suggested to
      reduce the risk of gestational diabetes (GDM). Several lifestyle intervention
      studies for pregnant women have reported dietary improvements after counselling.
      However, evidence concerning the effect of counselling initiated before pregnancy
      on diets is limited. METHODS: This randomised controlled study explored whether
      pre-pregnancy lifestyle counselling influenced food intakes, as well as whether
      changes in food intakes were associated with GDM. The participants comprised 75
      women with prior GDM and/or a body mass index >= 30 kg m-2 . Women were
      randomised into a control or an intervention group, and their food intakes were
      followed from pre-pregnancy to early pregnancy using a food frequency
      questionnaire. The control and intervention groups were combined to assess the
      association between changes in food intakes and GDM. The diagnosis of GDM was
      based on a 75-g oral glucose tolerance test conducted in the first and second
      trimester of pregnancy. RESULTS: Pre-pregnancy lifestyle counselling showed no
      major overall effect on food intakes. The intake of low-fat cheese increased
      significantly in women who did not develop GDM compared to women who did after
      adjusting for potential confounders (P = 0.028). This association was not
      observed for regular-fat cheese. CONCLUSIONS: The findings obtained in the
      present study suggest that an increased intake of low-fat but not regular-fat
      cheese between pre-pregnancy and early pregnancy is associated with a lower risk
      of GDM in high-risk women.

PMID- 29468750
TI  - Wheezing preschool children with early-onset asthma reveal a specific metabolomic
      profile.
AB  - BACKGROUND: Many children of preschool age present with recurrent wheezing. Most
      of them outgrow their symptoms, while some have early-onset asthma. Aim of this
      prospective preliminary study was to apply a metabolomic approach to see whether
      biochemical-metabolic urinary profiles can have a role in the early
      identification of the children with asthma. METHODS: Preschool children with
      recurrent wheezing were recruited and followed up for 3 years, after which they
      were classified as cases of transient wheezing or early-onset asthma. A urine
      sample was collected at recruitment and analyzed using a metabolomic approach
      based on UPLC mass spectrometry. RESULTS: Among 34 children aged 4.0 +/- 1.1
      years recruited, at the end of the 3-year follow-up, 16 were classified as having
      transient wheezing and 16 as cases of early-onset asthma. Through a joint
      multivariate and univariate statistical analyses, we identified a subset of
      metabolomic variables that enabled the 2 groups to be clearly distinguished. The
      model built using the identified variables showed an AUC = 0.99 and an AUC = 0.88
      on sevenfold full cross-validation (P = .002). CONCLUSIONS: Metabolomic urinary
      profile can discriminate preschoolers with recurrent wheezing who will outgrow
      their symptoms from those who have early-onset asthma. These results may pave the
      way to the characterization of early non-invasive biomarkers capable of
      predicting asthma development.

PMID- 29468751
TI  - New Control Over Silicone Synthesis using SiH Chemistry: The Piers-Rubinsztajn
      Reaction.
AB  - There is a strong imperative to synthesize polymers with highly controlled
      structures and narrow property ranges. Silicone polymers do not lend themselves
      to this paradigm because acids or bases lead to siloxane equilibration and loss
      of structure. By contrast, elegant levels of control are possible when using the
      Piers-Rubinsztajn reaction and analogues, in which the hydrophobic, strong Lewis
      acid B(C6 F5 )3 activates SiH groups, permitting the synthesis of precise
      siloxanes under mild conditions in high yield; siloxane decomposition processes
      are slow under these conditions. A broad range of oxygen nucleophiles including
      alkoxysilanes, silanols, phenols, and aryl alkyl ethers participate in the
      reaction to create elastomers, foams and green composites, for example, derived
      from lignin. In addition, the process permits the synthesis of monofunctional
      dendrons that can be assembled into larger entities including highly branched
      silicones and dendrimers either using the Piers-Rubinsztajn process alone, or in
      combination with hydrosilylation or other orthogonal reactions.

PMID- 29468752
TI  - Bi5+ , Bi(3-x)+ , and Oxygen Vacancy Induced BiOClx I1-x Solid Solution toward
      Promoting Visible-Light Driven Photocatalytic Activity.
AB  - BiOClx I1-x solid solutions with different band gaps were synthesized by
      adjusting the initial Cl to I molar ratios through a chemical precipitation
      method at room temperature. The structures, morphologies and optical properties
      of the samples were characterized by XRD, XPS, Raman, SEM, TEM and UV/Vis,
      respectively. The photocatalytic experiments showed that the BiOCl0.9 I0.1 sample
      totally decomposed a large concentration of 50 mg L-1 aqueous Rhodamine B (RhB)
      solution within 12 minutes under visible light irradiation (lambda>420 nm), which
      is 11 times higher than that of pure BiOI. Furthermore, the electron band
      structure and density of states of BiOCl, BiOI and BiOClx I1-x have been
      investigated using the DFT (density functional theory) calculation method and
      electrochemical methods. It was found that there are multiple crystal defects of
      Bi5+ , Bi(3-x)+ , and oxygen vacancies in the BiOClx I1-x samples. The results
      for Mott-Schottky plots and valence-band XPS spectra showed the position of
      conduction band (CB) for BiOCl0.9 I0.1 was up-shifted, which is favourable to the
      redox capacity for the photocatalysts. It could be elucidated that the
      synergistic effects of multiple crystal defects and unique band structure are
      critical to improving solar driven photocatalytic activity. This work provides a
      new highlight toward the construction of high property photocatalysts by tuning
      the crystal defect and band structure in a simple and efficient way.

PMID- 29468753
TI  - F1012-2 inhibits the growth of triple negative breast cancer through induction of
      cell cycle arrest, apoptosis, and autophagy.
AB  - Sesquiterpene lactones (SLs) are plant-derived constituents that have been proved
      to have potential antitumour activity. However, the intracellular molecular
      targets of SLs and the underlying molecular mechanisms have not been well
      elucidated. Here, we report that F1012-2, a novel SL active fraction, isolated
      from Eupatorium lindleyanum DC., can significantly inhibit the growth of triple
      negative breast cancer (TNBC) cells (MDA-MB-231 and MDA-MB-468) but has no
      obvious inhibitory effect on the growth of human mammary epithelial cells (MCF
      10A). The related mechanisms on cell growth inhibition of F1012-2 were
      demonstrated by inducing apoptosis in a caspase-dependent manner through the
      intrinsic pathway and extrinsic pathway. F1012-2 could also activate autophagy in
      TNBC cells. Simultaneously, we found that F1012-2-induced apoptosis was enhanced
      by inhibition of autophagy. Furthermore, F1012-2 could induce cell cycle arrest
      at G2/M phase with decreasing expression of cyclin B1, cdc2, and upregulating
      p21, p-cdc2. Also, F1012-2 activated Akt and p38 signalling pathways. In vivo,
      F1012-2 exhibited a potential antitumour effect in MDA-MB-231 xenografts without
      apparent toxicity. Taken together, our results identified that F1012-2 inhibited
      cell growth via multiple signalling pathways in vitro and in vivo. These data
      suggest that F1012-2 may be a potential natural active fraction for the treatment
      of TNBC.

PMID- 29468754
TI  - Prevalence of vitamin B12 deficiency in healthy Indian school-going adolescents
      from rural and urban localities and its relationship with various anthropometric
      indices: a cross-sectional study.
AB  - BACKGROUND: Micronutrient deficiency is a global health burden, especially among
      developing countries. The present cross-sectional study aimed to determine the
      prevalence of vitamin B12 deficiency in healthy Indian school-going adolescents,
      based on area of residence, sex and body mass index (BMI). Furthermore, the
      relationship of serum B12 concentration with dietary vitamin B12 intake and
      anthropometric indices was assessed among adolescents from rural and urban India.
      METHODS: A total of 2403 school-going adolescents (11-17 years) from National
      Capital Region and rural areas of Haryana, India were selected. Serum B12
      concentrations were estimated using an electrochemiluminescence immunoassay.
      Dietary assessments were conducted on 65% of total participants (n = 1556) by two
      24-h diet recalls. RESULTS: The prevalence of vitamin B12 deficiency in the total
      study population was 32.4% (rural: 43.9% versus urban: 30.1%, P < 0.001; male:
      34.4% versus female: 31.0%, P < 0.05; normal weight: 28.1%, versus overweight:
      39.8%, versus obese: 51.2%, P < 0.001). More than half (51.2%) of obese
      adolescents were vitamin B12 deficient. On multiple linear regression analysis,
      serum B12 in rural adolescents was associated with age (beta = -0.12, P < 0.05).
      Among urban adolescents, serum B12 was associated with BMI (beta = -0.08, P <
      0.05) and adjusted dietary vitamin B12 intake (beta = 0.14, P < 0.001). Serum
      vitamin B12 levels were found to be lower in rural females (beta = -0.12, P =
      0.030) and urban males (beta: 0.11, P < 0.001) compared to their respective
      contemporaries. CONCLUSIONS: Vitamin B12 deficiency was higher among rural school
      going adolescents. Boys had a higher B12 deficiency than girls. Inverse
      associations of serum B12 with adiposity indices were observed. Serum B12 levels
      were positively associated with dietary vitamin B12 intake.

PMID- 29468755
TI  - Impact of a mild scrotal heating on sperm chromosomal abnormality, acrosin
      activity and seminal alpha-glucosidase in human fertile males.
AB  - The aim of this study was to observe sperm aneuploidy, DNA integrity, seminal
      alpha-glucosidase (NAG) and acrosin activity (AA) under testicular heat stress
      (SH). Spermatozoa were obtained from 30 healthy adult volunteers subjected to
      scrotal warming at 43 degrees C for 30-40 min on two successive days per week for
      3 months between February 2012 and September 2016. Aniline blue (AB), acridine
      orange (AO) staining, TUNEL assay and FISH analysis to evaluate sperm function,
      sperm DNA integrity and chromosomal abnormalities were carried on before, during
      and after SH. Sperm AA and NAG was measured by microplate reader. The mean
      parameters of sperm parameters, AA and NAG were significantly decreased. In
      contrast, the mean percentage of sperm DNA fragmentation and the proportion of
      aneuploidy of chromosomes 13, 18, 21, X and Y were significantly increased for
      spermatozoa collected during SH versus before SH (p < .01-.001). After stopping
      scrotal heating for 3 months, most parameters were completely restored to pre-SH
      levels. Sperm parameters, sperm DNA integrity, chromosomes, AA and NAG are
      affected by scrotal exposure to constant SH temperatures several degrees over
      normal physiological temperature, and after treatment, these parameters were
      reversibly restored to the level before SH in adult men.

PMID- 29468756
TI  - Copper deposition in oligodendroglial cells in an autopsied case of
      hepatolenticular degeneration.
AB  - We present a case of hepatolenticular degeneration, so-called Wilson's disease
      (WD), in a 31-year-old Japanese man with broader deposition of copper in the
      liver, kidney and brain. The liver showed severe cirrhotic changes with
      macronodular pseudolobule formation, but there was little difference in
      immunohistochemical expression patterns of the copper transporter ATP7B between
      the control and present case. In the brain, there were both WD-related lesions
      such as the scattering of Opalski cells and changes caused by hepatic
      encephalopathy including the appearance of Alzheimer type II glia. Of note, we
      identified copper deposits in the systemic organs, including hepatocytes, renal
      tubules, and in broad areas of the brain. Surprisingly, as a result of further
      pursuit, copper accumulation in the brain was rarely identified in neuronal
      cells, but in Olig2-positive glial cells with double immunohistochemical
      staining. Together, this rare autopsied case suggests a novel cellular candidate
      affected by abnormal copper metabolism and the necessity to perform the systemic
      examination of copper deposition in WD.

PMID- 29468757
TI  - Anxiolytic and antidepressant activities of Pelargonium roseum essential oil on
      Swiss albino mice: Possible involvement of serotonergic transmission.
AB  - The anxiolytic and antidepressant activities of the Reunion Geranium (Pelargonium
      roseum Willd) essential oil (EO) were evaluated in male Swiss albino mice by
      intraperitoneal administration of 10, 20, and 50 mg/kg bw using elevated plus
      maze (EPM), open-field test (OFT), and forced swimming test (FST). Moreover, we
      evaluated whether the 5-HT1A and GABAA -benzodiazepine receptor systems are
      involved in the anxiolytic effects through the coadministration of WAY-100635 (a
      selective 5-HT1A receptor antagonist) and flumazenil (an antagonist of
      benzodiazepine). GC-MS revealed the monoterpene alcohols citronellol (35.9%) and
      geraniol (18.5%) as the main components of the P. roseum EO. EO was effective in
      increasing the total number of entries and time spent in the open arms of EPM
      whereas number of rearing in OFT was significantly decreased in comparison with
      the control. In the FST, immobility time decreased in EO treated mice.
      Pretreatment with WAY-100635, but not Flumazenil, was able to reverse the effects
      of the EO in the EPM and FST, indicating that the EO activity occurs via the
      serotonergic but not GABAergic transmission. Overall, results of this work showed
      significant anxiolytic and antidepressant activity of P. roseum EO and confirmed
      the traditional uses of Pelargonium species as calming agents.

PMID- 29468758
TI  - Evidence for Shikonin acting as an active inhibitor of human carboxylesterases 2:
      Implications for herb-drug combination.
AB  - Shikonin, a natural naphthoquinone compound derived from the herb Lithospermum
      erythrorhizon, is widely used for its various pharmacological activities.
      However, its potential interactions with other medications by inhibiting human
      carboxylesterases 2 (hCE2) remain unknown. In this study, the inhibitory effects
      of shikonin on the activity of hCE2 in human liver microsomes are investigated by
      using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6
      yl)-2-chloroacetamide (NCEN), and CPT-11 as substrates of hCE2. The results
      demonstrate that shikonin significantly inhibits the activity of hCE2 when FD and
      NCEN are used as substrates, whereas the half inhibition concentration value of
      shikonin increased by 5-30 times when CPT-11 was used as the substrate. The
      inhibition types of shikonin against hCE2 activity reflected by 3 substrates were
      all best fit to noncompetitive manners. In addition, shikonin was found to
      distinctly suppress endogenous hCE2 activity, characterized with attenuated
      fluorescence. Furthermore, for drugs metabolized by hCE2 with the similar binding
      sites with FD or NCEN, the estimated magnitudes of area under the curve variation
      were approximately 9-357% in the presence of shikonin. Also, the area under the
      curve of CPT-11 could be increased by 1-14% following administration of shikonin.
      These findings have clear clinical implications for the combination of shikonin
      and hCE2-metabolizing prodrugs.

PMID- 29468760
TI  - It is premature to expand access to medicinal cannabis in hopes of solving the US
      opioid crisis.

PMID- 29468761
TI  - Dietary patterns and risk of ulcerative colitis: a case-control study.
AB  - BACKGROUND: Recent evidence indicates a role for dietary factors in the
      pathogenesis of ulcerative colitis (UC). The aim of the present study was to
      investigate the relationship between dietary patterns and UC risk. METHODS: Sixty
      two newly diagnosed cases of UC and 124 healthy age and sex-matched controls were
      studied. Data on diet was measured using a validated country-specific food
      frequency questionnaire. Factor analysis was used to define major dietary
      patterns based on 28 food groups and nutrient content. RESULTS: After adjustment
      for confounding factors, subjects who were in the highest tertile of the healthy
      dietary pattern had a 79% lower risk of UC (odds ratio = 0.21, 95% confidence
      interval = 0.07-0.59, P = 0.003), whereas the consumption of an unhealthy dietary
      pattern was associated with a significantly increased risk of UC (odds ratio =
      3.39, 95% 95% confidence interval = 1.16-9.90, P = 0.027). CONCLUSIONS: The
      findings of the present study suggest that dietary patterns are associated with
      UC risk.

PMID- 29468762
TI  - Hypolipidemic activity and mechanisms of the total phenylpropanoid glycosides
      from Ligustrum robustum (Roxb.) Blume by AMPK-SREBP-1c pathway in hamsters fed a
      high-fat diet.
AB  - The aim of this study was to evaluate the hypolipidemic effect and mechanisms of
      total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume
      (LRTPG) in hamsters fed a high-fat diet and to discover bioactive components in
      HepG2 cell model induced by oleic acid. LRTPG of high (1.2 g/kg), medium (0.6
      g/kg), and low (0.3 g/kg) doses was administrated daily for 21 consecutive days
      in hamsters. We found that in hamsters fed a high-fat diet, LRTPG effectively
      reduced the concentrations of plasma triglycerides (TG), free fatty acid, total
      cholesterol, low-density lipoprotein cholesterol, and hepatic TG and total
      cholesterol. And the compounds acteoside, ligupurpuroside A, ligupurpuroside C,
      and ligupurpuroside D significantly inhibited lipid accumulation in HepG2 cell at
      the concentration of 50 MUmol/L. Mechanism research demonstrated that LRTPG
      increased the levels of phospho-AMP-activated protein kinase and phospho-sterol
      regulatory element binding protein-1c in liver, further to suppress the
      downstream lipogenic genes as stearoyl-CoA desaturase 1, glycerol-3-phosphate
      acyltransferase, 1-acylglycerol-3-phosphate O-acyltransferase 2, and
      diacylglycerol acyltransferase 2. In addition, LRTPG increased the hydrolysis of
      circulating TG by up-regulating lipoprotein lipase activities. These results
      indicate that LRTPG prevents hyperlipidemia via activation of hepatic AMP
      activated protein kinase-sterol regulatory element binding protein-1c pathway.

PMID- 29468763
TI  - Medical marijuana laws and adolescent marijuana use in the United States: a
      systematic review and meta-analysis.
AB  - AIMS: To conduct a systematic review and meta-analysis of studies in order to
      estimate the effect of US medical marijuana laws (MMLs) on past-month marijuana
      use prevalence among adolescents. METHODS: A total of 2999 papers from 17
      literature sources were screened systematically. Eleven studies, developed from
      four ongoing large national surveys, were meta-analyzed. Estimates of MML effects
      on any past-month marijuana use prevalence from included studies were obtained
      from comparisons of pre-post MML changes in MML states to changes in non-MML
      states over comparable time-periods. These estimates were standardized and
      entered into a meta-analysis model with fixed-effects for each study.
      Heterogeneity among the study estimates by national data survey was tested with
      an omnibus F-test. Estimates of effects on additional marijuana outcomes, of MML
      provisions (e.g. dispensaries) and among demographic subgroups were abstracted
      and summarized. Key methodological and modeling characteristics were also
      described. Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) guidelines were followed. RESULTS: None of the 11 studies found
      significant estimates of pre-post MML changes compared with contemporaneous
      changes in non-MML states for marijuana use prevalence among adolescents. The
      meta-analysis yielded a non-significant pooled estimate (standardized mean
      difference) of -0.003 (95% confidence interval = -0.012, +0.007). Four studies
      compared MML with non-MML states on pre-MML differences and all found higher
      rates of past-month marijuana use in MML states pre-MML passage. Additional tests
      of specific MML provisions, of MML effects on additional marijuana outcomes and
      among subgroups generally yielded non-significant results, although limited
      heterogeneity may warrant further study. CONCLUSIONS: Synthesis of the current
      evidence does not support the hypothesis that US medical marijuana laws (MMLs)
      until 2014 have led to increases in adolescent marijuana use prevalence. Limited
      heterogeneity exists among estimates of effects of MMLs on other patterns of
      marijuana use, of effects within particular population subgroups and of effects
      of specific MML provisions.

PMID- 29468764
TI  - Blood pressure lowering and anti-inflammatory effects of hesperidin in type 2
      diabetes; a randomized double-blind controlled clinical trial.
AB  - Elevated levels of reactive oxygen species under diabetic condition lead to
      vascular complications and inflammation. This study aimed to examine the effects
      of hesperidin supplement on blood pressure and inflammatory markers in type 2
      diabetes. In this research, 64 patients were randomly allocated to receive 500
      mg/day hesperidin or placebo capsules for 6 weeks. Data on systolic blood
      pressure (SBP), diastolic blood pressure, serum total antioxidant capacity (TAC),
      tumor necrosis factor alpha, interleukin 6 (IL-6), and high-sensitivity C
      reactive protein (hs-CRP) were collected at the baseline and at the end of the
      study. In the hesperidin group, SBP (122.7 +/- 8.5 vs. 119.0 +/- 7.4; p = .005),
      mean arterial blood pressure (94.2 +/- 5.5 vs. 91.8 +/- 5.5; p = .009), IL-6 (8.3
      +/- 2.1 vs. 7.4 +/- 1.8; p = .001), and hs-CRP (1.9 +/- 1.2 vs. 1.1 +/- 0.9; p <
      .000) decreased whereas TAC increased (0.74 +/- 0.1 vs. 0.82 +/- 0.1; p < .000)
      in comparison to the baseline values. There was a significant difference in mean
      percent change of SBP, diastolic blood pressure, mean arterial blood pressure,
      serum TAC, and inflammatory markers (tumor necrosis factor alpha, IL-6, and hs
      CRP) between hesperidin and control groups following intervention in adjusted
      models (p < .05). These results suggest that hesperidin may have antihypertensive
      and anti-inflammatory effects in type 2 diabetes.

PMID- 29468765
TI  - Outcomes of paediatric critical care asthma patients.
AB  - AIM: The aim of this study was to characterise patients with asthma admitted to
      an Australian paediatric intensive care unit (PICU). METHODS: This was a
      retrospective review of patients with asthma admitted to a university-affiliated,
      23-bed, tertiary PICU between January 2000 and December 2011, with a subset of
      pharmacotherapy and biochemical data from patients admitted between July 2007 and
      December 2011. RESULTS: A total of 589 admissions (501 patients) with asthma over
      12 years constituted 4.4% of all PICU admissions. Three patients died (0.6%). Non
      invasive ventilation (NIV) was used in 104 (17.7%) admissions, and 41 (7%) were
      invasively ventilated. On 12 (2%) occasions, patients received both NIV and
      invasive ventilation. Over 12 years, there was a significant trend to increased
      use of NIV, 11-39% (P < 0.0001), and invasive ventilation, 6-14% (P < 0.001). All
      received steroids and nebulised beta2-agonists. A total of 92% received
      intravenous (IV) beta2-agonists, 65% of these for less than 12 h. PICU and
      hospital stay were proportional to the duration of IV beta2-agonist infusion (P <
      0.0001). A total of 47.1% received IV magnesium sulphate, increasing from 19 to
      75% (P < 0.001). The majority (48%) were transferred directly to PICU from other
      hospitals. Median PICU stay was 1.04 days (0.72-1.63); hospital stay was 3.16
      days (2.29-4.71), and both were unchanged. CONCLUSIONS: Intensive care length of
      stay (LOS) was unchanged over 12 years. Both invasive and NIV and IV magnesium
      sulphate use increased. LOS was directly related to the duration of IV beta2
      agonist. Asthma patients admitted to PICU typically have a brief stay and have a
      fairly predictable course. Prospective studies could explore the contribution of
      IV agents and the role of NIV.

PMID- 29468766
TI  - Harms, benefits and the policing of cryptomarkets: a response to commentaries.

PMID- 29468767
TI  - Euthanasia and addiction: a comment from the Netherlands.

PMID- 29468768
TI  - Evaluation of a Realistic Cleansing Protocol for Preventing Discoloration of
      Denture Resins.
AB  - PURPOSE: To evaluate the efficacy of a realistic staining/cleansing protocol for
      long-term prevention of discoloration of denture base resins. MATERIALS AND
      METHODS: Sixty discs (20 * 2.5 mm) of auto- and heat-polymerizing denture acrylic
      resins were fabricated following manufacturer's instructions, polished on one
      side and stored in water (37 degrees C) for 24 hours before they were assigned
      randomly into 6 groups (3 for each material, n = 10) to receive 220 cycles of
      three immersion protocols. Group A was immersed in the following baths: (1)
      filtered coffee at 45 degrees C for 2 minutes, (2) tap water at 24 degrees C for
      20 seconds, (3) as bath 1, (4) as bath 2, (5) Corega Extradent cleansing solution
      at 45 degrees C for 3 minutes, and (6) water at 24 degrees C for 20 seconds.
      Group B was immersed in the four first baths of group A (without cleansing
      action) and group C in bath 1 for the cumulative action of 20 cycles (80 minutes
      in 45 degrees C coffee) and bath 2 for 40 seconds. A noncontact optical
      interferometric profilometer was used for qualitative evaluation of the specimens
      and a contact colorimeter to estimate color change values (DeltaEpsilon*ab) at
      baseline and every 20 cycles in the baths for a total of 220 cycles. Data were
      statistically analyzed using a 2-way-repeated measures ANOVA with Bonferoni
      multiple comparisons and trend analysis at alpha = 0.05 level of significance.
      RESULTS: Data indicated changes in color from 1.7 to 14.2 DeltaEpsilon*ab units.
      The highest values were related to the number of cycles and group B immersion
      protocol. Significant differences were found among immersion protocols (p <
      0.001) and immersion cycles (p < 0.001) with a significant interaction between
      protocols and cycles (p < 0.001) but not between denture resins (p = 0.991).
      CONCLUSION: The evaluated protocol A was found effective in preventing color
      changes in both denture resins even after a long period of action. Protocol C had
      a much lower staining effect on both resins than protocol B and behaved similarly
      to protocol A until 140 to 160 cycles. Therefore, it is probably not appropriate
      for use in short-term color stability experiments.

PMID- 29468769
TI  - Minimum spanning tree analysis of the human connectome.
AB  - One of the challenges of brain network analysis is to directly compare network
      organization between subjects, irrespective of the number or strength of
      connections. In this study, we used minimum spanning tree (MST; a unique, acyclic
      subnetwork with a fixed number of connections) analysis to characterize the human
      brain network to create an empirical reference network. Such a reference network
      could be used as a null model of connections that form the backbone structure of
      the human brain. We analyzed the MST in three diffusion-weighted imaging datasets
      of healthy adults. The MST of the group mean connectivity matrix was used as the
      empirical null-model. The MST of individual subjects matched this reference MST
      for a mean 58%-88% of connections, depending on the analysis pipeline. Hub nodes
      in the MST matched with previously reported locations of hub regions, including
      the so-called rich club nodes (a subset of high-degree, highly interconnected
      nodes). Although most brain network studies have focused primarily on cortical
      connections, cortical-subcortical connections were consistently present in the
      MST across subjects. Brain network efficiency was higher when these connections
      were included in the analysis, suggesting that these tracts may be utilized as
      the major neural communication routes. Finally, we confirmed that MST
      characteristics index the effects of brain aging. We conclude that the MST
      provides an elegant and straightforward approach to analyze structural brain
      networks, and to test network topological features of individual subjects in
      comparison to empirical null models.

PMID- 29468770
TI  - Pessary for prevention of preterm birth in twin pregnancy with short cervix: 3
      year follow-up study.
AB  - OBJECTIVE: A recent randomized clinical trial (ProTWIN) showed that a cervical
      pessary prevented preterm birth and improved neonatal outcome in women with
      multiple pregnancy and cervical length (CL) < 38 mm. In this follow-up study, the
      long-term developmental outcome of these children was evaluated at 3 years'
      corrected age. METHODS: This was a follow-up study of ProTWIN, a multicenter
      trial conducted between 2009 and 2012 in which asymptomatic women with a multiple
      pregnancy were randomized to placement of a cervical pessary or no intervention.
      Current follow-up and analysis were limited to mothers with a mid-trimester CL <
      38 mm (78 women (157 children) in the pessary group and 55 women (111 children)
      in the control group). At 3 years of corrected age, surviving children were
      invited for a Bayley Scales of Infant and Toddler Development-third edition
      (Bayley-III) assessment. Death after randomization or neurodevelopmental
      disability (Bayley-III score of <= 85, 1 SD below mean) rates were compared
      between the pessary and control groups, according to the intention-to-treat
      principle and using multiple imputation for missing data. Mean Bayley-III scores
      in surviving children were also assessed. A linear mixed-effects model was used
      to adjust for correlation between children of one mother. RESULTS: From the time
      of entry in the ProTWIN trial until follow-up at 3 years of age, a total of 27
      children had died (six (5%) in the pessary vs 21 (26%) in the control group; odds
      ratio (OR), 0.13; 95% CI, 0.04-0.48). Bayley-III outcomes were collected for
      173/241 (72%) surviving children (114 (75%) in the pessary vs 59 (66%) in the
      control group). The cumulative incidence of death or survival with a
      neurodevelopmental disability was 12 (10%) in the pessary vs 23 (29%) in the
      control group (OR, 0.26; 95% CI, 0.09-0.73). No statistical or clinically
      relevant differences were found with respect to cognitive, language and motor
      development among surviving children between the groups. Comparable results were
      found after multiple imputation. CONCLUSION: In women with twin pregnancy and a
      CL < 38 mm, the use of a cervical pessary strongly improved survival of the
      children without affecting neurodevelopment at 3 years' corrected age. Copyright
      (c) 2018 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29468771
TI  - Home blood-pressure monitoring in a hypertensive pregnant population.
AB  - OBJECTIVE: The majority of patients with chronic or gestational hypertension do
      not develop pre-eclampsia. Home blood-pressure monitoring (HBPM) has the
      potential to offer a more accurate and acceptable means of monitoring
      hypertensive patients during pregnancy compared with traditional pathways of
      frequent outpatient monitoring. The aim of this study was to determine whether
      HBPM reduces visits to antenatal services and is safe in pregnancy. METHODS: This
      was a case-control study of 166 hypertensive pregnant women, which took place at
      St George's Hospital, University of London. Inclusion criteria were: chronic
      hypertension, gestational hypertension or high risk of developing pre-eclampsia,
      no significant proteinuria (<= 1+ proteinuria on dipstick testing) and normal
      biochemical and hematological markers. Exclusion criteria were maternal age < 16
      years, systolic blood pressure > 155 mmHg or diastolic blood pressure > 100 mmHg,
      significant proteinuria (>= 2+ proteinuria on dipstick testing or
      protein/creatinine ratio > 30 mg/mmol), evidence of small-for-gestational age
      (estimated fetal weight < 10th centile), signs of severe pre-eclampsia,
      significant mental health concerns or insufficient understanding of the English
      language. Pregnant women in the HBPM group were taught how to measure and record
      their blood pressure using a validated machine at home and attended every 1-2
      weeks for assessment depending on clinical need. The control group was managed as
      per the local protocol prior to the implementation of HBPM. The two groups were
      compared with respect to number of visits to antenatal services and outcome.
      RESULTS: There were 108 women in the HBPM group and 58 in the control group.
      There was no difference in maternal age, parity, body mass index, ethnicity or
      smoking status between the groups, but there were more women with chronic
      hypertension in the HBPM group compared with the control group (49.1% vs 25.9%, P
      = 0.004). The HBPM group had significantly fewer outpatient attendances per
      patient (6.5 vs 8.0, P = 0.003) and this difference persisted when taking into
      account differences in duration of monitoring (0.8 vs 1.6 attendances per week, P
      < 0.001). There was no difference in the incidence of adverse maternal, fetal or
      neonatal outcome between the two groups. CONCLUSION: HBPM in hypertensive
      pregnancies has the potential to reduce the number of hospital visits required by
      patients without compromising maternal and pregnancy outcomes. Copyright (c) 2018
      ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29468772
TI  - The personal and community impact of a Scottish Men's Shed.
AB  - Social isolation and loneliness are known to be associated with increased
      morbidity and mortality. Therefore, reducing social isolation and loneliness may
      improve such outcomes. In relation to men's health, "Men's Sheds" have been shown
      as one mechanism to achieve this. Studies in Australia and England have shown
      social, health and personal benefits; however, this remains an area that has not
      yet been researched in Scotland. This study, therefore, aimed to assess the
      characteristics of attendees, self-reported motivations for and the values and
      benefits of attending the Shed from the views of the attendees themselves. The
      participants of the study were the members of a Men's Shed in the North of
      Scotland, which was initially set-up by a small number of core Shedders. A
      convenience sample was recruited by opportunistic interviewing of participants
      when they attended the Shed using a mixed methods approach from 1 to 15 November
      2016. In the absence of a validated questionnaire, a bespoke questionnaire was
      developed in several iterative stages. The answers to the questionnaire were
      transferred to an electronic database and analysed by frequency and thematic
      analysis. The participants (n = 31) had a mean age (SD) of 69.7 +/- 9.5 with
      96.8% being retired, thus the majority of the Shed users were older and retired.
      The results suggest that there were several benefits from attending the Shed,
      with an overwhelming majority of the sample reporting personal, social and health
      benefits-however, more research is needed to determine the magnitude of these.
      This study has also shown that the men attending the Shed frequently discussed
      health, which could potentially have a beneficial effect. The Shed therefore, as
      a community project, has the potential to have a positive impact on health
      welfare by focusing on the social aspects of life.

PMID- 29468774
TI  - Flexible parents: joint effects of handicapping and brood size manipulation on
      female parental care in Nicrophorus vespilloides.
AB  - Parental care is highly variable, reflecting that parents make flexible decisions
      in response to variation in the cost of care to themselves and the benefit to
      their offspring. Much of the evidence that parents respond to such variation
      derives from handicapping and brood size manipulations, the separate effects of
      which are well understood. However, little is known about their joint effects.
      Here, we fill this gap by conducting a joint handicapping and brood size
      manipulation in the burying beetle Nicrophorus vespilloides. We handicapped half
      of the females by attaching a lead weight to their pronotum, leaving the
      remaining females as controls. We also manipulated brood size by providing each
      female with 5, 20 or 40 larvae. In contrast to what we predicted, handicapped
      females spent more time provisioning food than controls. We also found that
      handicapped females spent more time consuming carrion. Furthermore, handicapped
      females spent a similar amount of time consuming carrion regardless of brood
      size, whereas controls spent more time consuming carrion as brood increased.
      Females spent more time provisioning food towards larger broods, and females were
      more likely to engage in carrion consumption when caring for larger broods. We
      conclude that females respond to both handicapping and brood size manipulations,
      but these responses are largely independent of each other. Overall, our results
      suggest that handicapping might lead to a higher investment into current
      reproduction and that it might be associated with compensatory responses that
      negate the detrimental impact of higher cost of care in handicapped parents.

PMID- 29468775
TI  - Spatiotemporal incidence rate data analysis by nonparametric regression.
AB  - To monitor the incidence rates of cancers, AIDS, cardiovascular diseases, and
      other chronic or infectious diseases, some global, national, and regional
      reporting systems have been built to collect/provide population-based data about
      the disease incidence. Such databases usually report daily, monthly, or yearly
      disease incidence numbers at the city, county, state, or country level, and the
      disease incidence numbers collected at different places and different times are
      often correlated, with the ones closer in place or time being more correlated.
      The correlation reflects the impact of various confounding risk factors, such as
      weather, demographic factors, lifestyles, and other cultural and environmental
      factors. Because such impact is complicated and challenging to describe, the
      spatiotemporal (ST) correlation in the observed disease incidence data has
      complicated ST structure as well. Furthermore, the ST correlation is hidden in
      the observed data and cannot be observed directly. In the literature, there has
      been some discussion about ST data modeling. But, the existing methods either
      impose various restrictive assumptions on the ST correlation that are hard to
      justify, or ignore partially or entirely the ST correlation. This paper aims to
      develop a flexible and effective method for ST disease incidence data modeling,
      using nonparametric local smoothing methods. This method can properly accommodate
      the ST data correlation. Theoretical justifications and numerical studies show
      that it works well in practice.

PMID- 29468773
TI  - A comparison of manual tracing and FreeSurfer for estimating hippocampal volume
      over the adult lifespan.
AB  - MRI has become an indispensable tool for brain volumetric studies, with the
      hippocampus an important region of interest. Automation of the MRI segmentation
      process has helped advance the field by facilitating the volumetric analysis of
      larger cohorts and more studies. FreeSurfer has emerged as the de facto standard
      tool for these analyses, but studies validating its output are all based on older
      versions. To characterize FreeSurfer's validity, we compare several versions of
      FreeSurfer software with traditional hand-tracing. Using MRI images of 262 males
      and 402 females aged 38 to 84, we directly compare estimates of hippocampal
      volume from multiple versions of FreeSurfer, its hippocampal subfield routines,
      and our manual tracing protocol. We then use those estimates to assess asymmetry
      and atrophy, comparing performance of different estimators with each other and
      with brain atrophy measures. FreeSurfer consistently reports larger volumes than
      manual tracing. This difference is smaller in larger hippocampi or older people,
      with these biases weaker in version 6.0.0 than prior versions. All methods tested
      agree qualitatively on rightward asymmetry and increasing atrophy in older
      people. FreeSurfer saves time and money, and approximates the same atrophy
      measures as manual tracing, but it introduces biases that could require
      statistical adjustments in some studies.

PMID- 29468776
TI  - Inter-shift variation in unscheduled intensive care unit transfers at a
      children's hospital.
AB  - BACKGROUND: The early detection of clinical deterioration and the prompt
      escalation of care is important but may be limited in the general ward,
      especially at night. Identifying variations between work shifts in the number of
      unscheduled in-hospital intensive care unit (ICU) transfers and emergency
      transfers involving life-threatening conditions may help implement targeted
      interventions to reduce delayed transfers and improve patient safety and
      outcomes. METHODS: All unscheduled ICU transfers in a tertiary children's
      hospital, from January 2013 to December 2016, were reviewed retrospectively. The
      transfers were categorized into safe transfers and adverse safety events (ASE).
      The 4 year cumulative numbers for each transfer category in each work shift (day,
      evening, and night) were assessed for comparison. An ASE was defined as transfer
      after cardiopulmonary resuscitation or tracheal intubation in the ward, or an
      unrecognized situation awareness failure event transfer, which was defined as
      previously reported. RESULTS: Of 244 unscheduled in-hospital ICU transfers, 167
      were safe transfers and 77 were ASE. The number of unscheduled transfers and of
      ASE was highest during the day shift (n = 133 and 40, respectively) and lowest
      during the night shift (n = 25 and 12, respectively). In contrast, the proportion
      of ASE in the unscheduled transfers was higher during the night shift (48%)
      compared with the day and evening shifts (30% and 31%, respectively).
      CONCLUSIONS: The occurrence of unscheduled ICU transfers was disproportionately
      low during the night shift, whereas the majority of ASE happened during the day
      shift. Future studies focusing on unravelling the reasons for such variations are
      warranted.

PMID- 29468777
TI  - Caring for crying babies: A mixed-methods study to understand factors influencing
      nurses' and doctors' management of infant colic.
AB  - AIM: The aim of this study was to determine the barriers and enablers influencing
      the uptake of two recommendations from a tertiary paediatric hospital's clinical
      practice guidelines by maternal and child health nurses (MCHNs) and emergency
      department (ED) doctors: (i) explaining normal crying; and (ii) avoiding
      attributing crying to gastro-oesophageal reflux (GOR) and limiting anti-reflux
      medication use. METHODS: The study was designed as 1-h focus group discussions,
      guided by the Theoretical Domains Framework, and a short questionnaire, with a
      purposive sample of MCHNs and ED doctors in Victoria, Australia in (March to
      September) 2015. Analyses were conducted by inductive content analysis to
      identify key barriers and enablers. RESULTS: A total of 53 MCHNs and 25 ED
      doctors participated in 11 discussions. For explaining normal crying, key
      enablers were: adequate experience/competency, perceiving it was their role to
      explain and belief it prevented over-medicalisation. The main barriers were time
      restriction and beliefs about parents' perceptions. For MCHNs, key barriers to
      avoid attributing crying to GOR were: lack of knowledge and confusion around
      their role in diagnosing GOR. For ED doctors, key barriers to limiting anti
      reflux medication were: parents requesting medication, concern about disrupting
      the parent-primary-care practitioner relationship and belief it was not their
      role to cease anti-reflux medication. CONCLUSIONS: Overall, MCHN and ED doctors
      were proficient in describing normal crying. However, several barriers to best
      practice were identified, including time constraints and belief about
      consequences of intervening. These results will be used to develop effective
      interventions to address the identified barriers and enablers to optimise the
      management of infant colic.

PMID- 29468778
TI  - Behavioral preference in sequential decision-making and its association with
      anxiety.
AB  - In daily life, people often make consecutive decisions before the ultimate goal
      is reached (i.e., sequential decision-making). However, this kind of decision
      making has been largely overlooked in the literature. The current study
      investigated whether behavioral preference would change during sequential
      decisions, and the neural processes underlying the potential changes. For this
      purpose, we revised the classic balloon analogue risk task and recorded the
      electroencephalograph (EEG) signals associated with each step of decision-making.
      Independent component analysis performed on EEG data revealed that four EEG
      components elicited by periodic feedback in the current step predicted
      participants' decisions (gamble vs. no gamble) in the next step. In order of time
      sequence, these components were: bilateral occipital alpha rhythm, bilateral
      frontal theta rhythm, middle frontal theta rhythm, and bilateral sensorimotor mu
      rhythm. According to the information flows between these EEG oscillations, we
      proposed a brain model that describes the temporal dynamics of sequential
      decision-making. Finally, we found that the tendency to gamble (as well as the
      power intensity of bilateral frontal theta rhythms) was sensitive to the
      individual level of trait anxiety in certain steps, which may help understand the
      role of emotion in decision-making.

PMID- 29468779
TI  - Probabilistic measures of climate change vulnerability, adaptation action
      benefits, and related uncertainty from maximum temperature metric selection.
AB  - Predictions of the projected changes in species distributions and potential
      adaptation action benefits can help guide conservation actions. There is
      substantial uncertainty in projecting species distributions into an unknown
      future, however, which can undermine confidence in predictions or misdirect
      conservation actions if not properly considered. Recent studies have shown that
      the selection of alternative climate metrics describing very different climatic
      aspects (e.g., mean air temperature vs. mean precipitation) can be a substantial
      source of projection uncertainty. It is unclear, however, how much projection
      uncertainty might stem from selecting among highly correlated, ecologically
      similar climate metrics (e.g., maximum temperature in July, maximum 30-day
      temperature) describing the same climatic aspect (e.g., maximum temperatures)
      known to limit a species' distribution. It is also unclear how projection
      uncertainty might propagate into predictions of the potential benefits of
      adaptation actions that might lessen climate change effects. We provide
      probabilistic measures of climate change vulnerability, adaptation action
      benefits, and related uncertainty stemming from the selection of four maximum
      temperature metrics for brook trout (Salvelinus fontinalis), a cold-water
      salmonid of conservation concern in the eastern United States. Projected losses
      in suitable stream length varied by as much as 20% among alternative maximum
      temperature metrics for mid-century climate projections, which was similar to
      variation among three climate models. Similarly, the regional average predicted
      increase in brook trout occurrence probability under an adaptation action
      scenario of full riparian forest restoration varied by as much as .2 among
      metrics. Our use of Bayesian inference provides probabilistic measures of
      vulnerability and adaptation action benefits for individual stream reaches that
      properly address statistical uncertainty and can help guide conservation actions.
      Our study demonstrates that even relatively small differences in the definitions
      of climate metrics can result in very different projections and reveal high
      uncertainty in predicted climate change effects.

PMID- 29468780
TI  - Efficacy of routine catheter tip culture in a neonatal intensive care unit.
AB  - BACKGROUND: Routine catheter tip cultures are not recommended because some cases
      of colonization, such as with Staphylococcus aureus, can lead to subsequent
      bacteremia. To evaluate the safety of colonization without antimicrobial
      treatment, as well as the effectiveness of routine catheter tip cultures in the
      neonatal intensive care unit (NICU), we performed a retrospective data analysis
      in a Japanese community hospital. METHODS: We reviewed all peripherally inserted
      central venous catheter tip culture results from the NICU ward between April 2012
      and June 2017 and noted outcome (i.e. antimicrobial treatment or subsequent
      infection). We then performed a cost analysis for routine catheter tip culturing
      on patients who were symptom free during the study period. RESULTS: Of the 93
      positive cases in 80 patients from 1,051 catheter tip cultures, seven patients
      had suspected infection and were treated with antimicrobials. The other 73
      symptom-free, positive patients had no subsequent or exacerbated symptoms
      indicative of an infection, and did not have antimicrobial treatment. The total
      cost for catheter tip culturing during the study period was Y548 731. After
      excluding patients with symptoms of infection at the time of culture, the
      efficacy of routine catheter tip cultures on symptom-free patients was estimated
      to be zero. CONCLUSION: Symptom-free colonization did not affect clinician
      management in this study, and all colonized patients without suspected infection
      were safely managed without antimicrobials. Furthermore, routine catheter tip
      culturing was not cost-effective; therefore, this practice may be no longer
      recommended in the NICU.

PMID- 29468781
TI  - What factors predict the passage of state-level e-cigarette regulations?
AB  - E-cigarettes are controversial products. They may help addicted smokers to
      consume nicotine in a less harmful manner or to quit tobacco cigarettes entirely,
      but these products may also entice youth into smoking. This controversy
      complicates e-cigarette regulation as any regulation may lead to health
      improvements for some populations, and health declines for other populations.
      Using data from 2007 to 2016, we examine factors that are plausibly linked with
      U.S. state e-cigarette regulations. We find that less conservative states are
      more likely to regulate e-cigarettes and that states with stronger tobacco
      lobbies are less likely to regulate e-cigarettes. This information can help
      policymakers as they determine how best to promote public health through
      regulation.

PMID- 29468782
TI  - Perceptions towards disability among social work students in Israel: Development
      and validation of a new scale.
AB  - Over the last decades, the disability movement has been advocating for a
      paradigmatic shift in how disability is perceived and managed: from a medical or
      individual perspective focusing on the person's body and mind to a social
      perspective emphasizing the context and barriers of disability. However, we still
      know little about the perceptions of helping professionals, particularly social
      workers who work closely with disabled people. Thus, the aim of the current study
      is to develop and validate a scale-Perceptions Toward Disability Scale (PTDS)-to
      measure how social workers view disability: as an individual or social category.
      This paper describes the three phases of the scale's construction. First, scale
      items were formulated and its content validity was examined. Next, a pilot of 30
      social workers completed a questionnaire and an initial exploratory factor
      analysis was conducted. In the third and main phase, the final draft was
      completed in 2016 by 565 Israeli social work students to assess its psychometric
      properties. Both exploratory and confirmatory factorial validity and discriminant
      validity analyses were conducted. The results of a confirmatory factor analysis
      revealed two distinct factors: an individual perspective of disability comprised
      of eight items (alpha = 0.77) and a social perspective of disability comprised of
      ten (alpha = 0.66). Subsequent analyses supported the scale's discriminant
      validity as indicated by the lack of an association between the Attitude Toward
      Disabled Persons Scale (ATDP) and the social model subscale (r = .13, p = .19)
      and by the weak negative relation with the individual model subscale (r = -.25, p
      = .01). These findings show that the PTDS possesses promising construct validity
      and provide support for its utility. This easy-to-administer instrument offers
      several practical benefits and can serve as a framework for further empirical
      research regarding social work practice with disabled people.

PMID- 29468783
TI  - Delayed cystoid macular oedema after uncomplicated laser peripheral iridotomy.

PMID- 29468784
TI  - Discovery of a Fungal Multicopper Oxidase That Catalyzes the Regioselective
      Coupling of a Tricyclic Naphthopyranone To Produce Atropisomers.
AB  - Atropisomeric dinapinones A1 and A2 (DPA1 and DPA2) were isolated from a culture
      of Talaromyces pinophilus FKI-3864. Monapinone coupling enzyme (MCE), which
      dimerizes naphthopyranone monapinone A (MPA), was purified from a cell-free
      extract of T. pinophilus FKI-3864. MCE regioselectively dimerizes MPA at the 8,8'
      positions to synthesize the atropisomers DPA1 and DPA2 in a ratio of
      approximately 1:2.5 without a cofactor. The optimal pH value and temperature for
      MCE were 4.0 and 50  degrees C, and the apparent Km and Vmax values for MPA were
      (72.7+/-23.2) MUm and (1.21+/-0.170) MUmol min-1  mg-1  protein. The MCE
      polypeptide is significantly homologous with multicopper oxidases. Heterologous
      expression of MCE and functional analysis confirmed that MCE catalyzes the
      regioselective coupling reaction of MPA to produce DPA. No fungal multicopper
      oxidase has previously been reported to catalyze regioselective intermolecular
      oxidative phenol coupling to produce naphthopyranone atropisomers.

PMID- 29468786
TI  - Ideal laser posterior capsulotomy size.

PMID- 29468785
TI  - Explaining the heterogeneity of functional connectivity findings in multiple
      sclerosis: An empirically informed modeling study.
AB  - To understand the heterogeneity of functional connectivity results reported in
      the literature, we analyzed the separate effects of grey and white matter damage
      on functional connectivity and networks in multiple sclerosis. For this, we
      employed a biophysical thalamo-cortical model consisting of interconnected
      cortical and thalamic neuronal populations, informed and amended by empirical
      diffusion MRI tractography data, to simulate functional data that mimic
      neurophysiological signals. Grey matter degeneration was simulated by decreasing
      within population connections and white matter degeneration by lowering between
      population connections, based on lesion predilection sites in multiple sclerosis.
      For all simulations, functional connectivity and functional network organization
      are quantified by phase synchronization and network integration, respectively.
      Modeling results showed that both cortical and thalamic grey matter damage
      induced a global increase in functional connectivity, whereas white matter damage
      induced an initially increased connectivity followed by a global decrease. Both
      white and especially grey matter damage, however, induced a decrease in network
      integration. These empirically informed simulations show that specific topology
      and timing of structural damage are nontrivial aspects in explaining functional
      abnormalities in MS. Insufficient attention to these aspects likely explains
      contradictory findings in multiple sclerosis functional imaging studies so far.

PMID- 29468787
TI  - Association of dialysis with in-hospital disability progression and mortality in
      community-onset stroke.
AB  - AIM: End-stage renal disease is associated with increased risk of cerebrovascular
      disease, but the effect on post-stroke clinical outcomes has not been thoroughly
      investigated. METHODS: Using the Japanese Diagnosis Procedure Combination
      database, which includes administrative claims and discharge abstract data, we
      examined the association between risk factors including dialysis therapy and in
      hospital disability progression or mortality in patients with community-onset
      stroke. We extracted data of patients aged >=20 years old who were admitted to
      the hospital within 3 days after onset of stroke between July 2010 and March
      2013. The disability level was divided into modified Rankin Scale (mRS) 0-1, 2-3,
      4-5, and 6 (death). Disability progression was defined as an increase in
      disability level. Odds ratios for in-hospital disability progression and
      mortality were calculated using logistic regression models. RESULTS: Of 435,403
      patients, 7,562 (1.7%) received dialysis therapy. The median length of stay was
      21 and 20 days for patients with and without dialysis, respectively. During the
      hospital stay, disability progressed in 100,402 (23.1%) patients and 45,919
      (10.5%) died. Patients on dialysis had a higher prevalence of disability
      progression (26.8%) and mortality (13.1%) compared to those without dialysis
      (23.0% and 10.5%, respectively). Dialysis was associated with an increased risk
      of in-hospital disability progression (odds ratio, 1.56; 95% confidence interval,
      1.47-1.66) and mortality (odds ratio 1.70; 95% confidence interval, 1.57-1.84).
      These risks were comparable among subtypes of stroke. CONCLUSIONS: Dialysis was
      associated with an increased risk of in-hospital disability progression and
      mortality among patients with community-onset stroke, regardless of stroke
      subtype.

PMID- 29468788
TI  - The Cyclic Hydrogen-Bonded 6-Azaindole Trimer and its Prominent Excited-State
      Triple-Proton-Transfer Reaction.
AB  - The compound 6-azaindole undergoes self-assembly by formation of N(1)-H???N(6)
      hydrogen bonds (H bonds), forming a cyclic, triply H-bonded trimer. The formation
      phenomenon is visualized by scanning tunneling microscopy. Remarkably, the H
      bonded trimer undergoes excited-state triple proton transfer (ESTPT), resulting
      in a proton-transfer tautomer emission maximized at 435 nm (325 nm of the normal
      emission) in cyclohexane. Computational approaches affirm the thermodynamically
      favorable H-bonded trimer formation and the associated ESTPT reaction. Thus,
      nearly half a century after Michael Kasha discovered the double H-bonded dimer of
      7-azaindole and its associated excited-state double-proton-transfer reaction, the
      triply H-bonded trimer formation of 6-azaindole and its ESTPT reaction are
      demonstrated.

PMID- 29468789
TI  - The Fourth Alloying Mode by Way of Anti-Galvanic Reaction.
AB  - Anti-galvanic reaction (AGR) not only defies classic galvanic theory but is a
      promising method for tuning the compositions, structures, and properties of noble
      metal nanoparticles. Employing AGR for the preparation of alloy nanoparticles has
      recently received great interest. Herein, we report an unprecedented alloying
      mode by way of AGR, in which foreign atoms induce structural transformation of
      the mother nanoparticles and enter the nanoparticles in a non-replacement
      fashion. A novel, active-metal-doped, gold nanoparticle was synthesized by this
      alloying mode, and its structure resolved. A CdSH motif was found in the
      protecting staples of the bimetal nanoparticle. DFT calculations revealed that
      the Au20 Cd4 (SH)(SR)19 nanoparticle is a 8e superatom cluster. Furthermore,
      although the Cd-doping does not essentially alter the absorption spectrum of the
      mother nanocluster, it distinctly enhances the stability and catalytic
      selectivity of the mother nanoclusters.

PMID- 29468790
TI  - Predictors of parental discretionary choice provision using the health action
      process approach framework: Development and validation of a self-reported
      questionnaire for parents of 4-7-year-olds.
AB  - AIM: Children's intake of discretionary choices is excessive. This study aimed to
      develop a questionnaire measuring parents' attitudes and beliefs towards limiting
      provision of discretionary choices, using the Health Action Process Approach
      model. METHODS: The questionnaire items were informed by the Health Action
      Process Approach model, which extends the Theory of Planned Behaviour to include
      both motivational (intention) and volitional (post-intention) factors that
      influence behaviour change. The questionnaire was piloted for content and face
      validity (expert panel, n = 5; parents, n = 4). Construct and predictive validity
      were examined in a sample of 178 parents of 4-7-year-old children who completed
      the questionnaire online. Statistical analyses included exploratory factor
      analyses, Cronbach's alpha and multiple linear regression. RESULTS: Pilot testing
      supported content and face validity. Principal component analyses identified
      constructs that aligned with the eight constructs of the Health Action Process
      Approach model. Internal consistencies were high for all subscales, in both the
      motivational (Cronbach's alpha 0.77-0.88) and volitional phase (Cronbach's alpha
      0.85-0.92). CONCLUSIONS: Initial results from validation tests support the
      development of a new questionnaire for measuring parent attitudes and beliefs
      regarding provision of discretionary choices to their 4-7-year-old children
      within the home. This new questionnaire can be used to gain greater insight into
      parents' attitudes and beliefs that influence ability to limit discretionary
      choices provision to children. Further research to expand understanding of the
      questionnaires' psychometric properties would be valuable, including confirmatory
      factor analysis and reproducibility.

PMID- 29468791
TI  - Effect of spatial arrangement and structure of hierarchically patterned fibrous
      scaffolds generated by a femtosecond laser on cardiomyoblast behavior.
AB  - Biological responses on biomaterials occur either on their surface or at the
      interface. Therefore, surface characterization is an essential step in the
      fabrication of ideal biomaterials for achieving effective control of the
      interaction between the material surface and the biological environment. Herein,
      we applied femtosecond laser ablation on electrospun fibrous scaffolds to
      fabricate various hierarchical patterns with a focus on the alignment of cells.
      We investigated the simultaneously stimulated response of cardiomyoblasts based
      on multiple topographical cues, including scales, oriented directions, and
      spatial arrangements, in the fibrous scaffolds. Our results demonstrated a
      synergistic effect on cell behaviors of one or more structural arrangements in a
      homogeneous orientation, whereas antagonistic effects were observed for cells
      arranged on a surface with heterogeneous directions. Taken together, these
      results indicate that our hierarchically patterned fibrous scaffolds may be
      useful tools for understanding the cellular behavior on fibrous scaffolds used to
      mimic an extracellular matrix-like environment. (c) 2018 Wiley Periodicals, Inc.
      J Biomed Mater Res Part A: 106A: 1732-1742, 2018.

PMID- 29468792
TI  - Polyprenols mitigate cognitive dysfunction and neuropathology in the APP/PS1
      mouse.
AB  - Alzheimer's disease (AD) is a very common neurodegenerative disorder in the
      elderly and brings considerable financial and social problems worldwide. In this
      study, polyprenols were firstly evaluated the effects on the cognitive deficits
      and neuropathology in APP/PS1 mice model of AD. At 3 months old, the APP/PS1 mice
      were divided into model group; polyprenols low, middle, and high dosage group;
      and positive drug group. Age-matched wild-type mice were chosen in control group.
      The administration by oral gavage lasted 6 months. Polyprenols treatment
      significantly improved cognitive impairment of double transgenic mice compared
      with vehicle control treatment in behavioral tests. In addition,
      immunohistochemistry and enzyme-linked immunosorbent assay showed that there were
      significantly reductions in neuritic plaques and the level of hyperphosphorylated
      tau in brain of polyprenols-treated mice. Furthermore, we found that polyprenols
      treatment reduced the apoptotic cells in brain sections of 9-month-old APP/PS1
      mice. These results reveal that polyprenols exert neuroprotective effects in
      APP/PS1 mice and could represent an effective treatment for AD.

PMID- 29468793
TI  - Capacitance for Carbon Capture.
AB  - Metal recycling: A sustainable, capacitance-assisted carbon capture and
      sequestration method can turn scrap metal and CO2 into metal carbonates at an
      attractive energy cost.

PMID- 29468794
TI  - Multiarm-polyethylene glycol-polyglutamic acid peptide dendrimer: Design,
      synthesis, and dissolving thrombus.
AB  - Thrombotic events affect many individuals in a number of ways, all of which can
      cause significant morbidity and mortality. Nattokinase (NK), as a novel
      thrombolytic drug, has been used for thrombolytic therapy. It not only possesses
      plasminogen activator activity, but also directly digests fibrin through limited
      proteolysis. However, it may undergo inactivation and denaturation in the harsh
      external environment. In this study, a multiarm-polyethylene glycol-polyglutamic
      acid peptide dendrimer was fabricated and used as a carrier for NK protection and
      delivery. Different arm numbers of polyethylene glycol-polyglutamic acid peptide
      dendrimers (x-PEG(G3 )x , x = 2, 4, 6, 8) were designed, prepared, and
      characterized by 1 H NMR and FTIR. Then, x-PEG(G3 )x were loaded with NK to form
      nanocomposites. Their size and morphology were determined by dynamic light
      scattering and transmission electron microscopy. Enzyme activity was evaluated
      via UV-Vis absorbance spectra, fluorescence spectra, circular dichroism spectra,
      and zeta potential measurements. The study reveals that the obtained x-PEG(G3 )x
      /NK nanocomposites possess high enzyme activity. In addition, the nanocomposites
      show increased viability of rat macrophage cells, and excellent thrombolysis
      ability in vitro and in vivo. This work establishes a multiarm-polyethylene
      glycol-polyglutamic acid peptide dendrimer with potential application in NK
      carrier and thrombolytic therapy. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater
      Res Part A: 106A: 1687-1696, 2018.

PMID- 29468795
TI  - Suboptimal use of pharmacological venous thromboembolism prophylaxis in cirrhotic
      patients.
AB  - BACKGROUND: Cirrhosis was previously perceived as a haemorrhagic disease state
      due to frequent associations with coagulopathy and bleeding. However, the
      coagulopathy of cirrhosis is complex with defects in both procoagulant and
      anticoagulant factors. Derangements in common laboratory indices of coagulation
      do not accurately reflect bleeding risk or protection from thrombotic events.
      AIMS: To assess the rate of pharmacological prophylaxis for venous
      thromboembolism (VTE) among hospital inpatients with cirrhosis and analyse
      factors associated with prophylaxis being inappropriately withheld. METHODS: A
      retrospective cohort study was performed in a tertiary teaching hospital.
      Patients included were admitted for greater than 48 h with discharge diagnosis
      codes corresponding to chronic liver disease and/or cirrhosis. The use of VTE
      chemoprophylaxis with enoxaparin was assessed in cirrhotic patients and non
      cirrhotic controls. Patient data collected included contraindications to
      prophylaxis, known high-risk varices, international normalised ratio (INR),
      creatinine, bilirubin, haemoglobin and platelet count. RESULTS: Of 108 patients
      with cirrhosis eligible for VTE prophylaxis, 61 (56.5%) received prophylaxis
      compared to 104 (96.3%) non-cirrhotic patients. Platelets and INR were
      significantly different between those who did and did not receive VTE
      prophylaxis. On multivariate analysis, platelet count and INR were independent
      predictors for VTE not being administered. CONCLUSION: The administration of
      chemoprophylaxis in accordance with the hospital guidelines was suboptimal in
      patients with cirrhosis. Platelet count and INR were independent predictors of
      prophylaxis use. Our results suggest persistent misperceptions that prolonged INR
      and thrombocytopenia predict bleeding risk in cirrhosis.

PMID- 29468796
TI  - Tracking the Oxygen Status in the Cell Nucleus with a Hoechst-Tagged
      Phosphorescent Ruthenium Complex.
AB  - Molecular oxygen in living cells is distributed and consumed inhomogeneously,
      depending on the activity of each organelle. Therefore, tractable methods that
      can be used to monitor the oxygen status in each organelle are needed to
      understand cellular function. Here we report the design of a new oxygen-sensing
      probe for use in the cell nucleus. We prepared "Ru-Hoechsts", each consisting of
      a phosphorescent ruthenium complex linked to a Hoechst 33258 moiety, and
      characterized their properties as oxygen sensors. The Hoechst unit shows strong
      DNA-binding properties in the nucleus, and the ruthenium complex shows oxygen
      dependent phosphorescence. Thus, Ru-Hoechsts accumulated in the cell nucleus and
      showed oxygen-dependent signals that could be monitored. Of the Ru-Hoechsts
      prepared in this study, Ru-Hoechst b, in which the ruthenium complex and the
      Hoechst unit were linked through a hexyl chain, showed the most suitable
      properties for monitoring the oxygen status. Ru-Hoechsts are probes with high
      potential for visualizing oxygen fluctuations in the nucleus.

PMID- 29468797
TI  - How would you help a colleague dealing with the stress of an adverse outcome? A
      report from #BlueJC.

PMID- 29468798
TI  - Tension-free vaginal tape for treatment of pure urodynamic stress urinary
      incontinence: efficacy and adverse effects at 17-year follow-up.
AB  - OBJECTIVE: To assess the efficacy and safety of retropubic tension-free vaginal
      tape (TVT) 17 years after implantation for the treatment of female pure stress
      urinary incontinence (SUI). PATIENTS AND METHODS: A prospective study was
      conducted in two urogynaecological units in two countries. All consecutive women
      with urodynamically proven pure SUI treated by TVT were included. Patients with
      mixed incontinence and/or anatomical evidence of pelvic organ prolapse were
      excluded. Data regarding subjective outcomes (International Consultation on
      Incontinence Questionnaire-Short Form, Patient Global Impression of Improvement,
      and patient satisfaction scores), objective cure (stress test) rates, and adverse
      events were collected during follow-up. Univariable analysis was performed to
      investigate outcomes. RESULTS: A total of 52 women underwent TVT implantation. At
      17-year follow-up, 46 women (88.4%) were available for the evaluation. We did not
      find any significant change in surgical outcomes during this time. At 17 years
      after surgery, 41 of 46 women (89.1%) declared themselves cured (P = 0.98).
      Similarly, at 17-year evaluation, 42 of 46 women (91.4%) were objectively cured.
      No significant deterioration in objective cure rates was observed over time (P
      for trend 0.50). The univariate analysis did not find any risk factor
      statistically associated with the recurrence of SUI. Of the 46 women, 15 (32.6%)
      reported the onset of de novo overactive bladder at 17-year follow-up. No other
      late complications were reported. CONCLUSIONS: The 17-year results of this study
      showed that TVT is a highly effective and safe option for the treatment of SUI.

PMID- 29468799
TI  - A Consensus Model: Shifting assessment practices in dietetics tertiary education.
AB  - AIM: The aim of this research was to evaluate a Consensus Model for competency
      based assessment. METHODS: An evaluative case study was used to allow a holistic
      examination of a constructivist-interpretivist programmatic model of assessment.
      Using a modified Delphi process, the competence of all 29 students enrolled in
      their final year of a Master of Nutrition and Dietetics course was assessed by a
      panel (with expertise in competency-based assessment; industry and academic
      representation) from a course e-portfolio (that included the judgements of
      student performance made by worksite educators) and a panel interview. Data were
      triangulated with assessments from a capstone internship. Qualitative descriptive
      studies with worksite educators (focus groups n = 4, n = 5, n = 8) and students
      (personal interviews n = 29) explored stakeholder experiences analysed using
      thematic analysis. RESULTS: Panel consensus was achieved for all cases by the
      third-round and corroborated by internship outcomes. For 34% of students this
      differed to the 'interpretations' of their performance made by their worksite
      educator/s. Emerging qualitative themes from stakeholder data found the model:
      (i) supported sustainable assessment practices; (ii) shifted the power
      relationship between students and worksite educators and (iii) provided a fair
      method to assess competence. To maximise benefits, more refinement, resources and
      training are required. CONCLUSIONS: This research questions competency-based
      assessment practices based on discrete placement units and supports a
      constructivist-interpretivist programmatic approach where evidence across a whole
      course of study is considered by a panel of assessors.

PMID- 29468800
TI  - The influence of matrix stiffness on the behavior of brain metastatic breast
      cancer cells in a biomimetic hyaluronic acid hydrogel platform.
AB  - Breast cancer brain metastasis marks the most advanced stage of breast cancer no
      longer considered curable with a median survival period of ~4-16 months. Apart
      from the genetic susceptibility (subtype) of breast tumors, brain metastasis is
      also dictated by the biophysical/chemical interactions of tumor cells with native
      brain microenvironment, which remain obscure, primarily due to the lack of
      tunable biomimetic in vitro models. To address this need, we utilized a
      biomimetic hyaluronic acid (HA) hydrogel platform to elucidate the impact of
      matrix stiffness on the behavior of MDA-MB-231Br cells, a brain metastasizing
      variant of the triple negative breast cancer line MDA-MB-231. We prepared HA
      hydrogels of varying stiffness (0.2-4.5 kPa) bracketing the brain relevant
      stiffness range to recapitulate the biophysical cues provided by brain
      extracellular matrix. In this system, we observed that the MDA-MB-231Br cell
      adhesion, spreading, proliferation, and migration significantly increased with
      the hydrogel stiffness. We also demonstrated that the stiffness based responses
      of these cells were mediated, in part, through the focal adhesion kinase
      phosphoinositide-3 kinase pathway. This biomimetic material system with tunable
      stiffness provides an ideal platform to further the understanding of
      mechanoregulation associated with brain metastatic breast cancer cells. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1832-1841, 2018.

PMID- 29468801
TI  - Re: Stillbirth: balancing patient preferences with clinical evidence: What about
      combining them into Informed Patient Choice?

PMID- 29468802
TI  - Synergistic effect of strontium, bioactive glass and nano-hydroxyapatite promotes
      bone regeneration of critical-sized radial bone defects.
AB  - Critical-sized bone defects constitute a major health issue in orthopedics and
      usually cause mal-unions due to an inadequate number of migrated progenitor cells
      into the defect site or their incomplete differentiation into osteogenic
      precursor cells. The current study aimed to develop an optimized osteoinductive
      and angiogenic scaffold by incorporation of strontium (Sr) and bioglass (BG) into
      gelatin/nano-hydroxyapatite (G/nHAp) seeded with bone marrow mesenchymal stem
      cells to enhance bone regeneration. The scaffolds were fabricated by a freeze
      drying technique and characterized in terms of morphology, structure, porosity
      and degradation rate. The effect of fabricated scaffolds on cell viability,
      attachment and differentiation into osteoblastic lineages was evaluated under in
      vitro condition. Micro computed tomography scan, histological and
      histomorphometric analysis were performed after implantation of scaffolds into
      the radial bone defects in rat. RT-PCR analysis showed that G/nHAp/BG/Sr scaffold
      significantly increased the expression level of osteogenic and angiogenic markers
      in comparison to other groups (P < 0.05). Moreover, the defects treated with the
      BMSCs-seeded scaffolds showed superior bone formation and mechanical properties
      compared to the cell-free scaffolds 4 and 12 weeks post-implantation. Finally,
      the BMSCs-seeded G/nHAp/BG/Sr scaffold showed the greatest bone regenerative
      capacity which was more similar to autograft. It is concluded that combination of
      Sr, BG, and nHAp can synergistically enhance the bone regeneration process. In
      addition, our results demonstrated that the BMSCs have the potential to
      considerably increase the bone regeneration ability of osteoinductive scaffolds.
      (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 29468804
TI  - VPS9 domain-containing proteins are essential for autophagy and endocytosis in
      Pyricularia oryzae.
AB  - Pyricularia oryzae is the causal pathogen of rice blast disease. Autophagy has
      been shown to play important roles in P. oryzae development and plant infection.
      The P. oryzae endosomal system is highly dynamic and has been shown to be
      associated with conidiogenesis and pathogenicity as well. To date, the crosstalk
      between autophagy and endocytosis has not been explored in P. oryzae. Here, we
      identified three P. oryzae VPS9 domain-containing proteins, PoVps9, PoMuk1 and
      PoVrl1. We found that PoVps9 and PoMuk1 are localized to vesicles and are each co
      localized with PoVps21, a recognized marker of early endosomes. Deletion of
      PoVPS9 resulted in severe defects in endocytosis and autophagosome degradation
      and impaired the localization of PoVps21 to endosomes. Additionally, deletion of
      the PoMUK1 gene in the DeltaPovps9 mutant background exhibited more severe
      defects in development, autophagy and endocytosis compared with the DeltaPovps9
      mutant. Pull-down assay showed that PoVps9 interacts with PoVps21, PoRab11 and
      PoRab1, which have been verified to participate in endocytosis. Furthermore,
      yeast two-hybrid and co-immunoprecipitation assays confirmed that PoVps9 directly
      interacts with the GDP form of PoVps21. Thus, PoVps9 is a key protein involved in
      autophagy and in endocytosis.

PMID- 29468803
TI  - Gene expression and ultrastructure of meso- and thermophilic methanotrophic
      consortia.
AB  - The sulfate-dependent, anaerobic oxidation of methane (AOM) is an important sink
      for methane in marine environments. It is carried out between anaerobic
      methanotrophic archaea (ANME) and sulfate-reducing bacteria (SRB) living in
      syntrophic partnership. In this study, we compared the genomes, gene expression
      patterns and ultrastructures of three phylogenetically different microbial
      consortia found in hydrocarbon-rich environments under different temperature
      regimes: ANME-1a/HotSeep-1 (60 degrees C), ANME-1a/Seep-SRB2 (37 degrees C) and
      ANME-2c/Seep-SRB2 (20 degrees C). All three ANME encode a reverse methanogenesis
      pathway: ANME-2c encodes all enzymes, while ANME-1a lacks the gene for N5,N10
      methylene tetrahydromethanopterin reductase (mer) and encodes a
      methylenetetrahydrofolate reductase (Met). The bacterial partners contain the
      genes encoding the canonical dissimilatory sulfate reduction pathway. During AOM,
      all three consortia types highly expressed genes encoding for the formation of
      flagella or type IV pili and/or c-type cytochromes, some predicted to be
      extracellular. ANME-2c expressed potentially extracellular cytochromes with up to
      32 hemes, whereas ANME-1a and SRB expressed less complex cytochromes (<= 8 and <=
      12 heme respectively). The intercellular space of all consortia showed nanowire
      like structures and heme-rich areas. These features are proposed to enable
      interspecies electron exchange, hence suggesting that direct electron transfer is
      a common mechanism to sulfate-dependent AOM, and that both partners synthesize
      molecules to enable it.

PMID- 29468805
TI  - Aligned nanofiber material supports cell growth and increases osteogenesis in
      canine adipose-derived mesenchymal stem cells in vitro.
AB  - Tissue engineering shows great promise for the treatment of degenerative
      diseases, including bone repair. Polymer nanofibers provide a three-dimensional
      (3-D) scaffold for attachment and growth of mesenchymal stem cells. Increasing
      evidence supports that fiber alignment on scaffolds plays a major role in the
      viability and differentiation of stem cells. We compared the cell viability of
      canine adipose tissue-derived mesenchymal stem cells (cADMSCs) cultured in the
      aligned- (NanoAlignedTM) and random- (NanoECMTM) oriented polycaprolactone (PCL)
      nanofiber-coated plates to control polystyrene tissue culture plates using a
      proliferation assay. Ability of the plates to induce differentiation of cADMSCs
      into osteocytes, adipocytes, and neurons was evaluated based on expression of the
      osteocyte markers, COL1A1 and osterix; adipocyte markers PPARgamma2 and LPL; and
      neuronal marker nestin using RT-PCR. Proliferation results demonstrated that
      aligned-oriented PCL nanofiber-coated plates were more suitable substrate for
      cADMSCs after 7 days in culture compared to random-oriented PCL nanofiber-coated
      or control plates. Additionally, we demonstrated that both 3-D PCL nanofiber
      coated plates were a better scaffold for cADMSCs differentiation into osteocytes
      compared to control plates. In conclusion, our results confirm that PCL nanofiber
      is a suitable tissue engineering material for use in regenerative medicine for
      canine patients in vivo. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part
      A: 106A: 1780-1788, 2018.

PMID- 29468806
TI  - Re: Subsequent reproductive outcome among women with peripartum cardiomyopathy: a
      nationwide study.

PMID- 29468807
TI  - Fatigue and quasi-static mechanical behavior of bio-degradable porous
      biomaterials based on magnesium alloys.
AB  - Magnesium and its alloys have the intrinsic capability of degrading over time in
      vivo without leaving toxic degradation products. They are therefore suitable for
      use as biodegradable scaffolds that are replaced by the regenerated tissues. One
      of the main concerns for such applications, particularly in load-bearing areas,
      is the sufficient mechanical integrity of the scaffold before sufficient volumes
      of de novo tissue is generated. In the majority of the previous studies on the
      effects of biodegradation on the mechanical properties of porous biomaterials,
      the change in the elastic modulus has been studied. In this study, variations in
      the static and fatigue mechanical behavior of porous structures made of two
      different Mg alloys (AZ63 and M2) over different dissolution times ( 6, 12, and
      24 h) have been investigated. The results showed an increase in the mechanical
      properties obtained from stress-strain curve (elastic modulus, yield stress,
      plateau stress, and energy absorption) after 6-12 h and a sharp decrease after 24
      h. The initial increase in the mechanical properties may be attributed to the
      accumulation of corrosion products in the pores of the porous structure before
      degradation has considerably proceeded. The effects of mineral deposition was
      more pronounced for the elastic modulus as compared to other mechanical
      properties. That may be due to insufficient integration of the deposited
      particles in the structure of the magnesium alloys. While the bonding of the
      parts being combined in a composite-like material is of great importance in
      determining its yield stress, the effects of bonding strength of both parts is
      much lower in determining the elastic modulus. The results of the current study
      also showed that the dissolution rates of the studied Mg alloys were too high for
      direct use in human body. (c) 2018 Authors Journal of Biomedical Materials
      Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      106A: 1798-1811, 2018.

PMID- 29468809
TI  - Proceedings of the Human Biology Association 42nd Annual Meeting, The Westin New
      Orleans Canal Place, New Orleans, LA, April 19-20, 2017.

PMID- 29468808
TI  - Prevalence of left ventricular hypertrabeculation/noncompaction among children
      with sickle cell disease.
AB  - OBJECTIVES: Incidence of sickle cell disease (SCD) in Ireland has dramatically
      increased. Disease survival has also steadily improved however cardiovascular
      manifestations remain important causes of morbidity. These include reports of
      left ventricular hypertrabeculation (LVHT)/noncompaction. We sought to
      investigate the prevalence of LVHT among a large cohort of children with SCD.
      METHODS: We retrospectively reviewed the records of all patients with a diagnosis
      of SCD who had undergone surveillance echocardiography at Our Lady's Children's
      Hospital Crumlin (OLCHC) from 1998 to 2015. Demographics, hemoglobin phenotype
      and treatment information was recorded. LV systolic function, evidence of LVHT,
      and possible pulmonary arterial hypertension was assessed. RESULTS: Two hundred
      thirty-six patients had echocardiograms available for interpretation. One hundred
      twenty-one (51.3%) were female; mean age was 11.3 years (+/- 4.1 years). Twenty
      six patients (11%) had features of LVHT on echocardiography. Eleven patients
      (4.7%) had borderline features of LVHT. Mean LVEDD across the whole cohort was
      4.2 +/- 0.69 cm, LVEDD z-score of 1.44 +/- 1.9, and mean LVSF was 37.3% +/-15.7%.
      There were no significant differences in terms of age, LVEDD, LVEDD z-score, or
      LVSF between patients with and those without LVHT. CONCLUSIONS: The prevalence of
      LVHT/noncompaction in children with SCD is lower than the adult population and LV
      systolic function is well preserved throughout our patient group. The mechanism
      behind the development of LVHT in this population remains speculative. Further
      work is required in this field. Sickle cell patients require longitudinal
      evaluation to ascertain changes in left ventricular function and the presence of
      LVHT/noncompaction.

PMID- 29468810
TI  - Cellular localization and biological effects of 20nm-gold nanoparticles.
AB  - Gold nanoparticles (AuNPs) have recently emerged as prominent vehicles for many
      biomedical applications from sensing to delivery. The relevant literature
      contains conflicting data about the effects of AuNPs on living cells. The aim of
      present study is the synthesis and characterization of AuNPs at nanoscale,
      tracking their cellular localization and determining their effects on cell
      viability, migration and angiogenesis. Within this scope, 20 nm AuNPs were
      synthesized and characterized using various spectrometric techniques to determine
      their size, shape and surface properties such as charge and texture. Two main
      cell types including mouse fibroblast (L929) and human cervix adenocarcinoma
      (HeLa) were used in the study to compare the biological effects of colloidal gold
      on both non-cancer and cancer cells. AuNPs were allowed to interact with HeLa
      cells to determine their intracellular localization. AuNPs were mainly attached
      to the cell membrane/membranous compartments and to be captured in small amounts
      in cytoplasmic vacuoles or to be distributed freely in the cytosol. Scratch assay
      results showed that AuNPs reduced cancer cell migration especially at increasing
      concentrations. According to the chick chorioallantoic membrane assay, AuNPs
      exhibited strong anti-angiogenetic properties and can inhibit vascularization
      during angiogenesis. In addition, the MTT assay confirmed that AuNP-treated cells
      caused concentration dependent cytotoxic effects on both cell types. As a result,
      AuNPs not only have inhibitory effects on cancer cells, but also possess
      antiangiogenic activity, thus making them a multipotent agent for cancer therapy.
      (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1708-1721,
      2018.

PMID- 29468811
TI  - Robotic rectal surgery in Korea: Analysis of a nationwide registry.
AB  - BACKGROUND: The aim of this study is to analyze the progress and the present
      state of application of robotic rectal surgery in Korea. METHODS: We used data
      from patients who underwent robotic, laparoscopic or open approaches for four
      types of operative procedures between 2006 and 2014: (1) anterior resection (AR),
      (2) low anterior resection (LAR), (3) intersphincteric resection (ISR) and (4)
      abdominoperineal resection (APR). RESULTS: The number of hospitals performing
      robotic rectal surgery has increased. Low anterior resection accounts for the
      largest percentage of robotic surgeries (mean 67.2%), and the number and
      proportion of ISRs performed robotically have increased rapidly (mean 22.6%). In
      addition, the dependence on robotic methods for ISR and APR increased rapidly
      over the study period. CONCLUSION: The use of robotic rectal surgery has widened
      over the last decade in Korea, and it has been convergent with surgeries for
      rectal lesions located near the anal verge.

PMID- 29468812
TI  - Modulation of Schlemm's canal endothelial cell stiffness via latrunculin loaded
      block copolymer micelles.
AB  - Increased stiffness of Schlemm's canal endothelial cells (SC cells) is a major
      contributing factor to the increased pressure characteristic of primary open
      angle glaucoma. New treatments for glaucoma are being developed using actin
      depolymerizers and rho kinase inhibitors to address this increased stiffness.
      However, these agents have off-target effects and are not as potent as had been
      hoped. We have developed a micellar nanocarrier assembled from poly(ethylene
      glycol)-bl-poly(propylene sulfide) copolymers capable of encapsulating
      latrunculin A (Lat A) with the goal of modulating SC cell stiffness. Lat A-loaded
      nanocarriers were similar in size and morphology to unloaded poly (ethylene
      glycol)-bl-poly(propylene sulfide) (PEG-bl-PPS) micelles, loaded Lat A at 62%
      encapsulation efficiency, and retained loaded Lat A for at least 22 days. The
      continued functional activity of Lat A following encapsulation within micelles
      was verified in murine macrophages, which are known to display decreased
      endocytosis in response to Lat A-dependent cytoskeletal disruption. Endocytic
      inhibition remained unchanged when comparing equal concentrations of micelle
      loaded versus free form Lat A. Uptake of Lat A-loaded micelles by human SC cells
      was verified in vitro with no sign of cytotoxicity, and modulation of SC cell
      stiffness was measured by atomic force microscopy. Lat A-loaded micelles
      significantly decreased SC cell stiffness, which resulted in visible changes in
      cell morphology as observed by confocal microscopy. Our results demonstrate that
      PEG-bl-PPS micelles represent a tunable platform for the controlled intracellular
      delivery of latrunculin. These self-assembled polymeric nanobiomaterials may
      support the rational design and engineering of delivery systems for the treatment
      of glaucoma. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:
      1771-1779, 2018.

PMID- 29468813
TI  - Optimus covered stent: Advanced covered stent technology for complex congenital
      heart disease.
AB  - AIM: To assess the acute results of the first human use of the Optimus covered
      stent in complex coarctation of the aorta. METHODS AND RESULTS: We successfully
      implanted the Optimus covered stent in eight cases in patients whose
      preprocedural anatomy looked challenging for currently available covered stents.
      Six of the patients had native coarctation with one recoarctation following
      surgical repair. There were no significant complications with reduction in the
      mean invasive gradient from 22 to 1 mm Hg. The length of stents used ranged from
      33 to 57 mm with a median shortening after expansion of 13%. Postprocedural
      follow-up with magnetic resonance imaging or computed tomography has not shown
      evidence of fracture or migration or renarrowing. The median duration of follow
      up is 10 months. CONCLUSIONS: Preliminary results show that the Optimus covered
      stent is safe and efficacious for use in patients with coarctation of challenging
      morphology. A systemic trial will be required to evaluate this stent for more
      widespread practice.

PMID- 29468814
TI  - Effects of substrate stiffness on dental pulp stromal cells in culture.
AB  - Dental pulp stromal cells (DPSCs) can be differentiated down lineages known to
      either express bone or dentin specific protein markers. Since the differentiation
      of cells can be heavily influenced by their environment, it may be possible to
      influence the osteogenic/odontogenic potential of DPSCs by modulating the
      mechanical properties of substrate on which they are grown. In this study, human
      DPSCs were grown with and without hydroxyapatite (HA) microparticles on a range
      of substrates including fibronectin-coated hydrogels and glass substrates, which
      represented an elastic moduli range of approximately 3 kPa-50 GPa, over a 21-day
      period. Alkaline phosphatase activity, osteopontin production, and mineralization
      were monitored. The presence of HA microparticles increased the relative degree
      of mineralized matrix produced by the cells relative to those in the same
      substrate and media condition without the HA microparticles. In addition,
      cultures with cells grown on stiffer substrates had higher ALP activity and
      higher degree of mineralization than those grown on softer substrates. This study
      shows that DPSCs are affected by the mechanical properties of their underlying
      growth substrate and by the presence of HA microparticles. In addition,
      relatively stiff substrates (>75 kPa) may be required for significant
      mineralization of these cultures. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater
      Res Part A: 106A: 1789-1797, 2018.

PMID- 29468815
TI  - Isothiocyanates: Translating the Power of Plants to People.
AB  - Isothiocyanates from cruciferous vegetables have been studied extensively in
      cells and in animals for their disease preventive and therapeutic effects.
      However, translating their utility to human populations has been both limited and
      challenging. Herein, clinical trials employing two isothiocyanates, sulforaphane
      (SFN; 1-isothiocyanato-4-(methylsulfinyl) butane) and phenethyl isothiocyanate
      (PEITC; 2-isothiocyanatoethylbenzene) that are isolated principally from broccoli
      and watercress, respectively, are summarized and discussed. Both of these
      compounds have been used in small human clinical trials, either within food
      matrices or as single agents, against a variety of diseases ranging from cancer
      to autism. Results suggest an opportunity to incorporate them, or more likely
      preparations derived from their source plants, into larger human disease
      mitigation efforts. The context for the applications of these compounds and
      plants in evidence-based food and nutritional policy is also evaluated.

PMID- 29468816
TI  - The cholinergic anti-inflammatory pathway revisited.
AB  - Inflammatory bowel disease negatively affects the quality of life of millions of
      patients around the world. Although the precise etiology of the disease remains
      elusive, aberrant immune system activation is an underlying cause. As such,
      therapies that selectively inhibit immune cell activation without broad
      immunosuppression are desired. Inhibition of immune cell activation preventing
      pro-inflammatory cytokine production through neural stimulation has emerged as
      one such treatment. These therapeutics are based on the discovery of the
      cholinergic anti-inflammatory pathway, a reflex arc that induces efferent vagal
      nerve signaling to reduce immune cell activation and consequently mortality
      during septic shock. Despite the success of preclinical and clinical trials, the
      neural circuitry and mechanisms of action of these immune-regulatory circuits are
      controversial. At the heart of this controversy is the protective effect of vagal
      nerve stimulation despite an apparent lack of neuroanatomical connections between
      the vagus and target organs. Additional studies have further emphasized the
      importance of sympathetic innervation of these organs, and that alternative
      neural circuits could be involved in neural regulation of the immune system. Such
      controversies also extend to the regulation of intestinal inflammation, with the
      importance of efferent vagus nerve signals in question. Experiments that better
      characterize these pathways have now been performed by Willemze et al. in this
      issue of Neurogastroenterology & Motility. These continued efforts will be
      critical to the development of better neurostimulator based therapeutics for
      inflammatory bowel disease.

PMID- 29468817
TI  - Urinary Excretion of Niacin Metabolites in Humans After Coffee Consumption.
AB  - SCOPE: Coffee is a major natural source of niacin in the human diet, as it is
      formed during coffee roasting from the alkaloid trigonelline. The intention of
      our study was to monitor the urinary excretion of niacin metabolites after coffee
      consumption under controlled diet. METHODS AND RESULTS: We performed a 4-day
      human intervention study on the excretion of major niacin metabolites in the
      urine of volunteers after ingestion of 500 mL regular coffee containing 34.8
      MUmol nicotinic acid (NA) and 0.58 MUmol nicotinamide (NAM). In addition to NA
      and NAM, the metabolites N1 -methylnicotinamide (NMNAM), N1 -methyl-2-pyridone-5
      carboxamide (2-Py), and nicotinuric acid (NUA) were identified and quantified in
      the collected urine samples by stable isotope dilution analysis (SIVA) using HPLC
      ESI-MS/MS. Rapid urinary excretion was observed for the main metabolites (NA,
      NAM, NMNAM, and 2-Py), with tmax values within the first hour after ingestion.
      NUA appeared in traces even more rapidly. In sum, 972 nmol h-1 of NA, NAM, NMNAM,
      and 2-Py were excreted within 12 h after coffee consumption, corresponding to 6%
      of the ingested NA and NAM. CONCLUSION: The results indicate regular coffee
      consumption to be a source of niacin in human diet.

PMID- 29468818
TI  - ZnO Nanopillar Coated Surfaces with Substrate-Dependent Superbactericidal
      Property.
AB  - ZnO nanopillars coated on various surfaces are able to kill adhered bacteria and
      fungi due to their physical structure through a rupturing mechanism. Remarkably,
      zinc foil and galvanized steel surfaces with ZnO nanopillar coatings demonstrate
      an excellent remote bacteria-killing property. Their bacterial killing efficacy
      is several orders higher than ZnO nanopillars coated on other surfaces as well as
      ZnO nanoparticles themselves. Mechanistic study shows that the nanostructure
      surface kills adhered microbial cells by rupturing the cell wall, while
      superoxide (* O2- ) released from the ZnO coating with electrons donated from
      zinc via the Zn/ZnO interface rather than photoirritation is responsible for the
      superior remote killing. The results of this study represent a novel mechanism of
      surface disinfection and its application in water disinfection is also
      demonstrated.

PMID- 29468819
TI  - Pt-Pd Bimetal Popcorn Nanocrystals: Enhancing the Catalytic Performance by
      Combination Effect of Stable Multipetals Nanostructure and Highly Accessible
      Active Sites.
AB  - Exploration of highly efficient electrocatalysts is significantly urgent for the
      extensive adoption of the fuel cells. Because of their high activity and super
      stability, Pt-Pd bimetal nanocrystals have been widely recognized as one class of
      promising electrocatalysts for oxygen reduction. This article presents the
      synthesis of popcorn-shaped Pt-Pd bimetal nanoparticles with a wide composition
      range through a facile hydrothermal strategy. The hollow-centered nanoparticles
      are surrounded by several petals and concave surfaces. By exploring the oxygen
      reduction reaction on the carbon supported Pt-Pd popcorns in perchloric acid
      solution, it is found that compared with the commercial Pt/C catalyst the present
      catalysts display superior catalytic performances in aspects of catalytic
      activity and stability. More importantly, the Pt-Pd popcorns display minor
      performance degradations through prolonged potential cycling. The enhanced
      performances can be mainly attributed to the unique popcorn structure of the Pt
      Pd components, which allows the appearance and long existence of the high active
      sites with more accessibility. The present work highlights the key roles of
      accessible high active sites in the oxygen reduction reaction, which will
      ultimately guide the design of highly durable Pt-Pd catalysts.

PMID- 29468820
TI  - Effects of curcumin consumption on human chronic diseases: A narrative review of
      the most recent clinical data.
AB  - Numerous clinical trials have investigated the potential beneficial effects of
      curcumin supplementation against several human chronic diseases. Up to now, it
      has been claimed that curcumin consumption may exert beneficial effects against
      several chronic diseases by promoting human health and preventing diseases. In
      this aspect, the present review aims to critically collect and in-depth summarize
      the most recent, well-designed clinical studies evaluating the potential
      beneficial effects of curcumin consumption on human health promotion and disease
      prevention. According to recent and well-designed clinical studies, curcumin
      consumption may benefit against obesity, metabolic syndrome, and diabetes.
      Moreover, curcumin consumption seems to exert a positive effect on people
      suffering from various types of cancer, fatty liver disease, depression,
      arthritis, skin diseases, gut inflammation, and symptoms of premenstrual
      syndrome. Due to the strong heterogeneity among the clinical studies concerning
      the exact effective curcumin dose and formulation, as well as the recommended
      treatment duration for each chronic disease, no precise and definitive
      conclusions could be drawn. Further large-scale prospective studies are strongly
      recommended, being well-designed as far as follow-up times, dosage, formulation,
      and duration of curcumin supplementation are concerned. Moreover, potential
      confounders in each specific chronic disease should carefully be taken into
      account in future studies.

PMID- 29468821
TI  - Urinary Metabolomics Profiles Associated to Bovine Meat Ingestion in Humans.
AB  - SCOPE: The impact of meat consumption on human health is widely examined in
      nutritional epidemiological studies, especially due to the connection between the
      consumption of red and processed meat and the risk of colon cancer. Food
      questionnaires do not assess the exposure to different methods of meat cooking.
      This study aimed to identify biomarkers of the acute ingestion of bovine meat
      cooked with two different processes. METHODS AND RESULTS: Non-targeted UPLC-MS
      metabolite profiling was done on urine samples obtained from 24 healthy
      volunteers before and 8 h after the ingestion of a single meal composed of
      intrinsically 15 N labelled bovine meat, either cooked at 55  degrees C for 5 min
      or at 90  degrees C for 30 min. A discriminant analysis extension of independent
      components analysis was applied to the mass spectral data. After meat ingestion,
      the urinary excretion of 1-methylhistidine, phenylacetylglutamine, and short- and
      medium-chained acylcarnitines was observed. 15 N labelling was detected in these
      metabolites, thus confirming their origin from ingested meat. However, no
      difference was observed in urinary metabolomic profiles according to the meat
      cooking process used. CONCLUSION: Meat ingestion led to the excretion of several
      nitrogen-containing compounds, but although a metabolic signature was detected
      for meat ingestion, the impact of the cooking process was not detectable at the
      level of urinary metabolic signature in our experimental conditions.

PMID- 29468822
TI  - Phycoerythrin-Derived Tryptic Peptide of a Red Alga Pyropia yezoensis Attenuates
      Glutamate-Induced ER Stress and Neuronal Senescence in Primary Rat Hippocampal
      Neurons.
AB  - SCOPE: Glutamate excitotoxicity has been observed in association with
      neurodegenerative disorders. This study aimed to investigate whether a
      phycoerythrin-derived tryptic peptide of Pyropia yezoensis (PYP) reduces
      glutamate-induced excitotoxicity and neuronal senescence in primary rat
      hippocampal neurons. METHODS AND RESULTS: Glutamate exposure (100 MUm) decreased
      cell viability and increased expression of endoplasmic reticulum (ER) stress
      response protein glucose-regulated protein 78 (GRP78) starting at 60 min
      following glutamate exposure, which was prevented by pretreating the neurons with
      PYP (1 MUg mL-1 ). The glutamate-induced increase in GRP78 expression was
      downregulated by blocking N-methyl-d-aspartate (NMDA) receptor with MK801 (10
      MUm) and inhibiting c-Jun N-terminal kinase (JNK) phosphorylation with SP600125
      (10 MUm). Moreover, phosphorylation of JNK was decreased by blockade of NMDA
      receptor. The PYP pretreatment downregulated glutamate-induced increase in GRP78
      expression and JNK phosphorylation, and this effect was abolished by inhibiting
      tropomyosin-related kinase B (TrkB) receptor, phosphatidylinositiol 3-kinase, and
      extracellular signal-regulated kinase (ERK)1/2 using cyclotraxin B (200 nm),
      LY294002 (20 MUm), and SL327 (10 MUm), respectively. In addition, PYP
      downregulated increase in GRP78 expression, senescence-associated beta
      galactosidase activity, and neurite degeneration in aging hippocampal neurons.
      CONCLUSION: These findings indicate that activation of TrkB receptor-mediated
      ERK1/2 by PYP attenuates glutamate-induced ER stress, which may improve the
      survival of hippocampal neurons with age.

PMID- 29468823
TI  - Molecularly Selective Regulation of Delivery Fluxes by Employing Supramolecular
      Interactions in Layer-by-Layer Films.
AB  - The molecularly selective regulation of molecular fluxes in a biomaterial that
      delivers multiple chemical species simultaneously is still beyond the reach of
      materials scientists. A delivery material was developed by means of the layer-by
      layer (LbL) technique. This material discriminatively regulates the delivery flux
      of bioactive small molecules, as represented by a peptide containing the RGD
      fragment and the chemotherapy drug doxorubicin (DOX). Molecularly selective flux
      regulations in LbL films are realized through fast, reversible supramolecular
      interactions between cyclodextrin and its guests. The mechanism underlining the
      delivery strategy is that supramolecular interactions promote molecular loading
      and slow down diffusion-dependent release. In a preliminary survey of materials
      parameters, a maximum difference in cell viability between healthy human
      bronchial epithelial cells and cancer cells (A549) was realized.

PMID- 29468824
TI  - Towards High-Performance Aqueous Sodium-Ion Batteries: Stabilizing the
      Solid/Liquid Interface for NASICON-Type Na2 VTi(PO4 )3 using Concentrated
      Electrolytes.
AB  - Aqueous Na-ion batteries may offer a solution to the cost and safety issues of
      high-energy batteries. However, substantial challenges remain in the development
      of electrode materials and electrolytes enabling high performance and long cycle
      life. Herein, we report the characterization of a symmetric Na-ion battery with a
      NASICON-type Na2 VTi(PO4 )3 electrode material in conventional aqueous and "water
      in-salt" electrolytes. Extremely stable cycling performance for 1000 cycles at a
      high rate (20 C) is found with the highly concentrated aqueous electrolytes owing
      to the formation of a resistive but protective interphase between the electrode
      and electrolyte. These results provide important insight for the development of
      aqueous Na-ion batteries with stable long-term cycling performance for large
      scale energy storage.

PMID- 29468825
TI  - The co-occurrence of anaemia and stunting in young children.
AB  - Anaemia and stunting are prevalent nutritional problems among children of low
      income countries that have profound effects on development, morbidity, and
      mortality. Many use a single conceptual framework to identify the basic
      determinants of these and other forms of malnutrition. One would expect that
      problems with matching underlying determinants should co-occur in affected
      individuals to a greater degree than by chance. In 2 populations of children-ages
      6-18 months in Bihar, India, (n = 5,664) and 6-36 months in Lambayeque, Peru (n =
      688)-we measured the frequency of the co-occurrence of anaemia and stunting. We
      compared this value with the value expected by chance, the product of the
      prevalence of anaemia and stunting, using a chi-square test. We also built
      logistic regression models for each condition. The frequency of co-occurrence in
      the Indian population was 21.5%, and in the Peruvian population, it was 30.4%,
      which are similar to frequencies expected by chance, 21.3% (p = .97) and 31.5% (p
      = .85). In Peru, anaemia was associated with age and consumption of treated
      water. Stunting was associated with age, sex, dietary diversity, hand washing,
      language spoken, and wealth. In India, anaemia was associated with age, sex,
      caste, dietary diversity, and household hunger. Stunting was associated with age,
      sex, caste, wealth, and maternal illiteracy. Despite some basic shared factors,
      anaemia and stunting are more independent than commonly assumed. Interventions
      that target children based on 1 condition may miss children with the other form
      of malnutrition.

PMID- 29468826
TI  - Rhodium(II)-Catalyzed Reaction of 1-Tosyl-1,2,3-triazoles with Morita-Baylis
      Hillman Adducts: Synthesis of 3,4-Fused Pyrroles.
AB  - A cascade reaction of rhodium azavinylcarbenes with Morita-Baylis-Hillman (MBH)
      adducts enables a novel synthetic approach to 3,4-fused pyrroles. The cascade
      reaction begins with the insertion of O-H bond into rhodium azavinylcarbenes,
      subsquent sigmatropic rearrangement provides substituted alpha,beta-unsaturated
      cyclic ketone intermediates. Then the intramolecular aza Michael
      addition/oxidative aromatization sequence give rise to a wide range of 3,4-fused
      pyrroles in good yields, and with excellent functional group compatibility.

PMID- 29468827
TI  - Exploration of Antigen Induced CaCO3 Nanoparticles for Therapeutic Vaccine.
AB  - Therapeutic vaccines possess particular advantages and show promising potential
      to combat burdening diseases, such as acquired immunodeficiency syndrome,
      hepatitis, and even cancers. An efficient therapeutic vaccine would strengthen
      the immune system and eventually eliminate target cells through cytotoxic T
      lymphocytes (CTLs). Unfortunately, insufficient efficacy in triggering such an
      adaptive immune response is a problem that remains unsolved. To achieve efficient
      cellular immunity, antigen-presenting cells must capture and further cross
      present disease-associated antigens to CD8 T cells via major histocompatibility
      complex I molecules. Here, a biomimetic strategy is developed to fabricate
      hierarchical ovalbumin@CaCO3 nanoparticles (OVA@NP, ~500 nm) under the templating
      effect of antigen OVA. Taking advantage of the unique physicochemical properties
      of crystalline vaterite, cluster structure, and high loading, OVA@NP can
      efficiently ferry cargo antigen to dendritic cells and blast lysosomes for
      antigen escape to the cytoplasm. In addition, the first evidence that the
      physical stress from generated CO2 induces autophagy through the LC3/Beclin 1
      pathways is presented. These outcomes cooperatively promote antigen cross
      presentation, elicit CD8 T cell proliferation, ignite a potent and specific CTL
      response, and finally achieve prominent tumor therapy effects.

PMID- 29468828
TI  - Liquid Exfoliation of Colloidal Rhenium Disulfide Nanosheets as a Multifunctional
      Theranostic Agent for In Vivo Photoacoustic/CT Imaging and Photothermal Therapy.
AB  - Near-infrared light-mediated theranostic agents with superior tissue penetration
      and minimal invasion have captivated researchers in cancer research in the past
      decade. Herein, a probe sonication-assisted liquid exfoliation approach for
      scalable and continual synthesis of colloidal rhenium disulfide nanosheets, which
      is further explored as theranostic agents for cancer diagnosis and therapy, is
      reported. Due to high-Z element of Re (Z = 75) and significant photoacoustic
      effect, the obtained PVP-capped ReS2 nanosheets are evaluated as bimodality
      contrast agents for computed tomography and photoacoustic imaging. In addition,
      utilizing the strong near-infrared absorption and ultrahigh photothermal
      conversion efficiency (79.2%), ReS2 nanosheets could also serve as therapeutic
      agents for photothermal ablation of tumors with a tumor elimination rate up to
      100%. Importantly, ReS2 nanosheets show no obvious toxicity based on the
      cytotoxicity assay, serum biochemistry, and histological analysis. This work
      highlights the potentials of ReS2 nanosheets as a single-component theranostic
      nanoplatform for bioimaging and antitumor therapy.

PMID- 29468829
TI  - Disease progression and variation in clinical practice for isolated bicuspid
      aortic valve in children.
AB  - BACKGROUND: Disease progression of an isolated bicuspid aortic valve (BAV) in
      children is poorly understood and adult management guidelines may not be
      applicable. Thus, we sought to evaluate disease progression of pediatric isolated
      BAV and its relationship to current management practices. METHODS: Children with
      a BAV and <=mild aortic stenosis (AS) and/or aortic regurgitation (AR) at the
      time of initial evaluation were included in this retrospective cohort study
      (1/2005-12/2014). Outcomes included change in z-scores for aortic root and
      ascending aorta diameters, cardiac interventions, adverse outcomes, recommended
      follow-up interval, and frequency of cardiac imaging studies at each follow up
      evaluation, as well as AS/AR severity at final evaluation. Outcomes were analyzed
      using generalized mixed-effect models with subject and provider clustering.
      RESULTS: BAV disease progression was evaluated in 294 subjects over 4.1 +/- 2.4
      (range 0.2-9.5) years. Ascending aorta z-scores increased by 0.1/year (P < .001)
      but aortic root diameter z-scores were unchanged. AS and/or AR progressed to
      >mild in 9 (3%), 1 subject underwent cardiac intervention, and none had a major
      complication. Management was evaluated in 454 subjects (1343 encounters) with 27
      different cardiologists. The average recommended follow-up interval was 1.5 +/-
      0.9 years. Younger age at diagnosis, greater aortic root or ascending aorta z
      score at diagnosis, >=mild AS/AR at follow-up, and earlier diagnosis era were
      associated with shorter recommended follow-up interval (P < .001 for all).
      Imaging was obtained at 87% of follow-up encounters and was associated with age
      at encounter with children >=12 years most frequently imaged (P < .001). Provider
      accounted for 14% of variability in recommended follow-up interval and 24% of
      imaging variability (P < .001 for both). CONCLUSIONS: We found little to no
      evidence of disease progression in children with an isolated BAV. Given the low
      risk, close follow-up and frequent cardiac imaging for BAV surveillance may not
      be warranted for children.

PMID- 29468831
TI  - The evolutionary stability of attenuators that mask information about animals
      that social partners can exploit.
AB  - Signals and cues are fundamental to social interactions. A well-established
      concept in the study of animal communication is an amplifier, defined as a trait
      that does not add extra information to that already present in the original cue
      or signal, but rather enhances the fidelity with which variation in the original
      cue or signal is correctly perceived. Attenuators as the logical compliment of
      amplifiers: attenuators act to reduce the fidelity with which variation in a
      signal or cue can be reliably evaluated by the perceivers. Where amplifiers
      reduce the effect of noise on the perception of variation, attenuators add noise.
      Attenuators have been subject to much less consideration than amplifiers;
      however, they will be the focus of our theoretical study. We utilize an extension
      of a well-established model incorporated signal or cue inaccuracy and costly
      investments by emitter and perceiver in sending and attending to the signal or
      cue. We present broad conditions involving some conflict of interest between
      emitter and perceiver where it may be advantageous for emitters to invest in
      costly attenuators to mask cues from potential perceivers, and a subset of these
      conditions where the perceiver may be willing to invest in costly anti
      attenuators to mitigate the loss of information to them. We demonstrate that
      attenuators can be evolutionary stable even if they are costly, even if they are
      sometimes disadvantageous and even if a perceiver can mount counter-measures to
      them. As such, we feel that attenuators of cues may be deserving of much more
      research attention.

PMID- 29468830
TI  - Concise Review: Is Cardiac Cell Therapy Dead? Embarrassing Trial Outcomes and New
      Directions for the Future.
AB  - Stem cell therapy is a promising strategy for tissue regeneration. The
      therapeutic benefits of cell therapy are mediated by both direct and indirect
      mechanisms. However, the application of stem cell therapy in the clinic is
      hampered by several limitations. This concise review provides a brief
      introduction into stem cell therapies for ischemic heart disease. It summarizes
      cell-based and cell-free paradigms, their limitations, and the benefits of using
      them to target disease. Stem Cells Translational Medicine 2018;7:354-359.

PMID- 29468832
TI  - Becoming Breastfeeding Friendly Index: Development and application for scaling-up
      breastfeeding programmes globally.
AB  - Global efforts to further improve exclusive breastfeeding rates have not been
      successful, in part because effective scaling-up frameworks and roadmaps have not
      been developed. The Becoming Breastfeeding Friendly (BBF) toolbox includes an
      evidence-based index, the BBF Index (BBFI), to guide the development and tracking
      of large scale, well-coordinated, multisector national breastfeeding promotion
      programmes. This paper describes the development of the BBFI, which is grounded
      in the Breastfeeding Gear Model complex adaptive systems framework. The BBFI was
      developed by the BBF Steering Committee in collaboration with a high-level
      Technical Advisory Group following the Delphi consensus methodology. Key
      benchmarks and definitions were informed by evidence-based health, nutrition, and
      newborn survival initiatives identified from the academic and grey literature.
      The BBFI consists of 8 gears (54 benchmarks): Advocacy (4); Political Will (3);
      Legislation and Policies (10); Funding and Resources (4); Training and Program
      Delivery (17); Promotion (3); Research and Evaluation (10); and Coordination,
      Goals, and Monitoring (3). Scores are generated for 8 gear scores plus a total
      country score to gauge the scaling-up enabling environment. The BBFI provides an
      evidence-based index to assist countries in (a) assessing their readiness to
      scale up breastfeeding programmes and (b) tracking scaling-up progress.

PMID- 29468833
TI  - Identification of Three Rheumatoid Arthritis Disease Subtypes by Machine Learning
      Integration of Synovial Histologic Features and RNA Sequencing Data.
AB  - OBJECTIVE: In this study, we sought to refine histologic scoring of rheumatoid
      arthritis (RA) synovial tissue by training with gene expression data and machine
      learning. METHODS: Twenty histologic features were assessed in 129 synovial
      tissue samples (n = 123 RA patients and n = 6 osteoarthritis [OA] patients).
      Consensus clustering was performed on gene expression data from a subset of 45
      synovial samples. Support vector machine learning was used to predict gene
      expression subtypes, using histologic data as the input. Corresponding clinical
      data were compared across subtypes. RESULTS: Consensus clustering of gene
      expression data revealed 3 distinct synovial subtypes, including a high
      inflammatory subtype characterized by extensive infiltration of leukocytes, a low
      inflammatory subtype characterized by enrichment in pathways including
      transforming growth factor beta, glycoproteins, and neuronal genes, and a mixed
      subtype. Machine learning applied to histologic features, with gene expression
      subtypes serving as labels, generated an algorithm for the scoring of histologic
      features. Patients with the high inflammatory synovial subtype exhibited higher
      levels of markers of systemic inflammation and autoantibodies. C-reactive protein
      (CRP) levels were significantly correlated with the severity of pain in the high
      inflammatory subgroup but not in the others. CONCLUSION: Gene expression analysis
      of RA and OA synovial tissue revealed 3 distinct synovial subtypes. These labels
      were used to generate a histologic scoring algorithm in which the histologic
      scores were found to be associated with parameters of systemic inflammation,
      including the erythrocyte sedimentation rate, CRP level, and autoantibody levels.
      Comparison of gene expression patterns to clinical features revealed a
      potentially clinically important distinction: mechanisms of pain may differ in
      patients with different synovial subtypes.

PMID- 29468835
TI  - Gastrointestinal Symptoms in Patients Receiving Dialysis: A Systematic Review.
AB  - AIM: To describe the prevalence of all Gastrointestinal (GI) symptoms reported by
      dialysis patients, as well as the tools being used for diagnosis. BACKGROUND: GI
      symptoms are commonly reported in patients having haemodialysis (HD) and
      peritoneal dialysis (PD), but there are multiple definitions and assessment tools
      reported in the literature. METHODS: A comprehensive systematic review was
      undertaken using five databases (Embase, Medline, CINAHL, Psycinfo and Web of
      Science) between 1996 and 2017. Articles were critically appraised using the
      Newcastle Ottawa Scale (NOS). Data collected was analysed in a Microsoft Excel
      spreadsheet. RESULTS: Thirty studies (24 cross sectional, 6 cohort) met the
      inclusion criteria. In total 5,161 patients were studied (3,804 HD and 1,507 PD).
      Fifteen studies included HD, five includedPD and ten included both dialysis
      modalities. GI symptoms were heterogeneous, with the reported prevalence highly
      dependent on the definitions used, inclusion/exclusion criteria, assessment tools
      and methods used. The most prevalent symptoms were constipation, indigestion,
      abdominal pain and reflux. Medication use and dietary data were poorly reported.
      The most common tools used were Gastrointestinal Symptom Rating Scale (GSRS),
      Rome II and Rome III. Constipation was more common in HD patients than PD
      patients. Indigestion, abdominal pain and reflux were commonly reported in both
      dialysis modalities. CONCLUSIONS: GI symptoms are highly prevalent in people on
      dialysis; however, the evidence base is limited and further investigation of
      preventable causes and potential interventions such as medications and diet is
      required in future research.

PMID- 29468834
TI  - Peripheral blood clinical laboratory variables associated with outcomes following
      combination nivolumab and ipilimumab immunotherapy in melanoma.
AB  - Both the combination of nivolumab + ipilimumab and single-agent anti-PD-1
      immunotherapy have demonstrated survival benefit for patients with advanced
      melanoma. As the combination has a high rate of serious side effects, further
      analyses in randomized trials of combination versus anti-PD-1 immunotherapy are
      needed to understand who benefits most from the combination. Clinical laboratory
      values that were routinely collected in randomized studies may provide
      information on the relative benefit of combination immunotherapy. To prioritize
      which clinical laboratory factors to ultimately explore in these randomized
      studies, we performed a single-center, retrospective analysis of patients with
      advanced melanoma who received nivolumab + ipilimumab either as part of a
      clinical trial (n = 122) or commercial use (n = 87). Baseline routine laboratory
      values were correlated with overall survival (OS) and overall response rate
      (ORR). Kaplan-Meier estimation and Cox regression were performed. Median OS was
      44.4 months, 95% CI (32.9, Not Reached). A total of 110 patients (53%) responded
      (CR/PR). Significant independent variables for favorable OS included the
      following: high relative eosinophils, high relative basophils, low absolute
      monocytes, low LDH, and a low neutrophil-to-lymphocyte ratio. These newly
      identified factors, along with those previously reported to be associated with
      anti-PD-1 monotherapy outcomes, should be studied in the randomized trials of
      nivolumab + ipilimumab versus anti-PD-1 monotherapies to determine whether they
      help define the patients who benefit most from the combination versus anti-PD-1
      alone.

PMID- 29468836
TI  - Combining advantages: Direct correlation of two-dimensional microcomputed
      tomography datasets onto histomorphometric slides to quantify three-dimensional
      bone volume in scaffolds.
AB  - Microcomputed tomography (mCT) belongs to the most powerful tools for the three
      dimensional (3D) assessment of bone. While it is possible to refer to landmarks
      in mCT scans of actual bone structure, the assessment of calcified osteoid within
      scaffolds is problematic, due to the missing morphological correlates. Therefore,
      bone formation within scaffolds is mostly analyzed using indirect parameters such
      as changes in volume or surface alteration, preserving histomorphometry the gold
      standard in the direct analysis of bone formation. The presented method combines
      the advantages of mCT and histomorphometry: by creating an overlay image of the
      exact same histomorphometric and mCT slice, a grey-value-threshold representing
      calcified tissue was defined. Compared to the scaffolds global threshold, a
      direct evaluation of bone formation within scaffolds is possible by mCT-applied
      on the whole dataset, evaluation of bone volume is achievable. Two groups of
      human mesenchymal-stem-cell-seeded beta-Tricalciumphosphate-scaffolds were
      analyzed: whilst group B was stimulated with 0.1 ug/mL Bone Morphogenetic Protein
      7, group A remained unstimulated during in vivo differentiation. Strong
      correlations (r > 0.8) were obtained between percentage bone area in mCT and
      histomorphometry, as well as for 3D bone volume. Using the presented method, 3D
      bone volume can be directly estimated within scaffolds by combination of
      histomorphometric and mCT-analysis. (c) 2018 Wiley Periodicals, Inc. J Biomed
      Mater Res Part A: 106A: 1812-1821, 2018.

PMID- 29468837
TI  - Nanomaterial Preparation by Extrusion through Nanoporous Membranes.
AB  - Template synthesis represents an important class of nanofabrication methods.
      Herein, recent advances in nanomaterial preparation by extrusion through
      nanoporous membranes that preserve the template membrane without sacrificing it,
      which is termed as "non-sacrificing template synthesis," are reviewed. First, the
      types of nanoporous membranes used in nanoporous membrane extrusion applications
      are introduced. Next, four common nanoporous membrane extrusion strategies:
      vesicle extrusion, membrane emulsification, precipitation extrusion, and
      biological membrane extrusion, are examined. These methods have been utilized to
      prepare a wide range of nanomaterials, including liposomes, emulsions,
      nanoparticles, nanofibers, and nanotubes. The principle and historical context of
      each specific technology are discussed, presenting prominent examples and
      evaluating their positive and negative features. Finally, the current challenges
      and future opportunities of nanoporous membrane extrusion methods are discussed.

PMID- 29468838
TI  - Anti-vascular endothelial growth factors treatment of wet age-related macular
      degeneration: from neurophysiology to cost-effectiveness.

PMID- 29468839
TI  - The iron-stress activated RNA 1 (IsaR1) coordinates osmotic acclimation and iron
      starvation responses in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - In nature, microorganisms are exposed to multiple stress factors in parallel.
      Here, we investigated the response of the model cyanobacterium Synechocystis sp.
      PCC 6803 to simultaneous iron limitation and osmotic stresses. Iron is a major
      limiting factor for bacterial and phytoplankton growth in most environments.
      Thus, bacterial iron homeostasis is tightly regulated. In Synechocystis, it is
      mediated mainly by the transcriptional regulator FurA and the iron-stress
      activated RNA 1 (IsaR1). IsaR1 is an important riboregulator that affects the
      acclimation of the photosynthetic apparatus to iron starvation in multiple ways.
      Upon increases in salinity, Synechocystis responds by accumulating the compatible
      solute glucosylglycerol (GG). We show that IsaR1 overexpression causes a
      reduction in the de novo GG synthesis rate upon salt shock. We verified the
      direct interaction between IsaR1 and the 5'UTR of the ggpS mRNA, which in turn
      drastically reduced the de novo synthesis of the key enzyme for GG synthesis,
      glucosylglycerol phosphate synthase (GgpS). Thus, IsaR1 specifically interferes
      with the salt acclimation process in Synechocystis, in addition to its primary
      regulatory function. Moreover, the salt-stimulated GgpS production became reduced
      under parallel iron limitation in WT - an effect which is, however, attenuated in
      an isaR1 deletion strain. Hence, IsaR1 is involved in the integration of the
      responses to different environmental perturbations and slows the osmotic
      adaptation process in cells suffering from parallel iron starvation.

PMID- 29468840
TI  - Surface Oxidation of AuNi Heterodimers to Achieve High Activities toward
      Hydrogen/Oxygen Evolution and Oxygen Reduction Reactions.
AB  - Although much attention has been paid to the exploration of highly active
      electrocatalysts, especially catalysts for hydrogen evolution reaction (HER),
      oxygen evolution reaction (OER) and oxygen reduction reaction (ORR), the
      development of multifunctional catalysts remains a challenge. Here, we utilize
      AuNi heterodimers as the starting materials to achieve high activities toward
      HER, OER and ORR. The HER and ORR activities in an alkali environment are similar
      to those of Pt catalysts, and the OER activity is very high and better than that
      of commercial IrO2 . Both the experimental and calculated results suggest that
      the surface oxidation under oxidative conditions is the main reason for the
      different activities. The NiO/Ni interface which exists in the as-synthesized
      heterodimers contributes to high HER activity, the Ni(OH)2 -Ni-Au interface and
      the surface Ni(OH)2 obtained in electrochemical conditons gives rise to promising
      ORR and OER activities, respectively. As a comparison, a Au@Ni core-shell
      structure is also synthesized and examined. The core-shell structure shows lower
      activities for HER and OER than the heterodimers, and reduces O2 selectively to
      H2 O2 . The work here allows for the development of a method to design
      multifunctional catalysts via the partial oxidation of a metal surface to create
      different active centers.

PMID- 29468841
TI  - Development, Verification, and Prediction of Osimertinib Drug-Drug Interactions
      Using PBPK Modeling Approach to Inform Drug Label.
AB  - Osimertinib is a potent, highly selective, irreversible inhibitor of epidermal
      growth factor receptor (EGFR) and T790M resistance mutation. In vitro metabolism
      data suggested osimertinib is a substrate of cytochrome P450 (CYP)3A4/5, a weak
      inducer of CYP3A, and an inhibitor of breast cancer resistance protein (BCRP). A
      combination of in vitro data, clinical pharmacokinetic data, and drug-drug
      interaction (DDI) data of osimertinib in oncology patients were used to develop
      the physiologically based pharmacokinetic (PBPK) model and verify the DDI data of
      osimertinib. The model predicted the observed monotherapy concentration profile
      of osimertinib within 1.1-fold, and showed good predictability (within 1.7-fold)
      to the observed peak plasma concentration (Cmax ) and area under the curve (AUC)
      DDI ratio changes, when co-administered with rifampicin, itraconazole, and
      simvastatin, but not with rosuvastatin. Based on observed clinical data and PBPK
      simulations, the recommended dose of osimertinib when dosed with strong CYP3A
      inducers is 160 mg once daily. PBPK modeling suggested no dose adjustment with
      moderate and weak CYP3A inducers.

PMID- 29468842
TI  - Shielding verification and neutron dose evaluation of the Mevion S250 proton
      therapy unit.
AB  - For passive scattering proton therapy systems, neutron contamination is the main
      concern both from an occupational and patient safety perspective. The Mevion S250
      compact proton therapy system is the first of its kind, offering an in-room
      cyclotron design which prompts more concern for shielding assessment. The purpose
      of this study was to accomplish an in-depth evaluation of both the shielding
      design and in-room neutron production at our facility using both Monte Carlo
      simulation and measurement. We found that the shielding in place at our facility
      is adequate, with simulated annual neutron ambient dose equivalents at 30 cm
      outside wall/door perimeter ranging from background to 0.07 mSv and measured dose
      equivalents ranging from background to 0.06 mSv. The in-room measurements reveal
      that the H*/D decreases when the distance from isocenter and field size
      increases. Furthermore, the H*/D generally increases when the angle around
      isocenter increases. Our results from in-room measurements show consistent trends
      with our Monte Carlo model of the Mevion system.

PMID- 29468843
TI  - GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG in Green
      Tea.
AB  - SCOPE: The molecular mechanisms whereby gallates in green tea exert metabolic
      effects are poorly understood. METHODS AND RESULTS: We found that GPRC6A, a multi
      ligand-sensing G-protein-coupled receptor that regulates energy metabolism, sex
      hormone production, and prostate cancer progression, is a target for gallates.
      Sodium gallate (SG), gallic acid (GA) > ethyl gallate (EG) > octyl gallate (OG)
      dose dependently activated ERK in HEK-293 cells transfected with GPRC6A but not
      in non-transfected controls. SG also stimulated insulin secretion in beta-cells
      isolated from wild-type mice similar to the endogenous GPRC6A ligands,
      osteocalcin (Ocn) and testosterone (T). Side-chain additions to create OG
      resulted in loss of GPRC6A agonist activity. Another component of green tea,
      epigallocatechin 3-gallate (EGCG), dose-dependently inhibited Ocn activation of
      GPRC6A in HEK-293 cells transfected with GPRC6A and blocked the effect of Ocn in
      stimulating glucose production in CH10T1/2 cells. Using structural models of the
      venus fly trap (VFT) and 7-transmembrane (7-TM) domains of GPRC6A, calculations
      suggest that l-amino acids and GA bind to the VFT, whereas EGCG is calculated to
      bind to sites in both the VFT and 7-TM. CONCLUSION: GA and EGCG have offsetting
      agonist and antagonist effects on GPRC6A that may account for the variable
      metabolic effect of green tea consumption.

PMID- 29468845
TI  - Nomenclature for factors of the HLA system, update December 2017.

PMID- 29468844
TI  - Are Older Adults With Symptomatic Knee Osteoarthritis Less Active Than the
      General Population? Analysis From the Osteoarthritis Initiative and the National
      Health and Nutrition Examination Survey.
AB  - OBJECTIVE: To compare objectively measured physical activity in older adults with
      symptomatic knee osteoarthritis (OA) with similarly aged adults without
      osteoarthritis (OA) or knee symptoms from the general population. METHODS: We
      included people ages 50-85 years with symptomatic knee OA from the Osteoarthritis
      Initiative (OAI, n = 491), and ages 50-85 years from the general population using
      National Health and Nutrition Examination Survey (NHANES, n = 449) data. A
      uniaxial accelerometer was worn for >=10 hours/day for >=4 days in the NHANES
      group in 2003-2004 and in the OAI group in 2008-2010. We calculated time spent in
      moderate-to-vigorous physical activity (MVPA in minutes/day) and described
      differences in MVPA and demographic variables between the samples. We conducted
      matched-pairs sensitivity analyses to further evaluate the role of potential
      confounders. RESULTS: Both cohorts had similarly low levels of physical activity
      in age- and sex-specific strata. Time in MVPA ranged from a median of 1-22
      minutes/day in people with symptomatic knee OA, and from 1-24 minutes/day in the
      general population without OA or knee pain. These results were similar in
      sensitivity analyses. CONCLUSION: Time spent in MVPA was similarly low in those
      with symptomatic knee OA as in older adults without knee pain or OA.

PMID- 29468847
TI  - Nomenclature for factors of the HLA system, update October 2017.

PMID- 29468846
TI  - Nomenclature for factors of the HLA system, update November 2017.

PMID- 29468848
TI  - Time trend analysis of long term outcome of patients with haematological
      malignancies admitted at dutch intensive care units.
AB  - A few decades ago, the chances of survival for patients with a haematological
      malignancy needing Intensive Care Unit (ICU) support were minimal. As a
      consequence, ICU admission policy was cautious. We hypothesized that the long
      term outcome of patients with a haematological malignancy admitted to the ICU has
      improved in recent years. Furthermore, our objective was to evaluate the
      predictive value of the Acute Physiology and Chronic Health Evaluation (APACHE)
      II score. A total of 1095 patients from 5 Dutch university hospitals were
      included from 2003 until 2015. We studied the prevalence of patients'
      characteristics over time. By using annual odds ratios, we analysed which
      patients' characteristics could have had influenced possible trends in time. A
      approximated mortality rate was compared with the ICU mortality rate, to study
      the predictive value of the APACHE II score. Overall one-year mortality was 62%.
      The annual decrease in one-year mortality was 7%, whereas the APACHE II score
      increased over time. Decreased mortality rates were particularly observed in high
      risk patients (acute myeloid leukaemia, old age, low platelet count, bleeding as
      admission reason and need for mechanical ventilation within 24 h of ICU
      admission). Furthermore, the APACHE II score overestimates mortality in this
      patient category.

PMID- 29468849
TI  - Antiviral activities of Clinacanthus nutans (Burm.f.) Lindau extract against
      Cyprinid herpesvirus 3 in koi (Cyprinus carpio koi).
AB  - Cyprinid herpesvirus 3 (CyHV-3) or koi herpesvirus (KHV) is a virulent viral
      infection in common carp and koi. The disease has caused global epizootic and
      economic loss in fish aquaculture and in the wild. Clinacanthus nutans (Burm. f.)
      Lindau is a well-known medicinal plant used in Thai traditional medicine.
      Virucidal effects of the plant extract against human herpes simplex virus have
      been reported. In this study, C. nutans crude extract was tested for antiviral
      activities against CyHV-3 in koi carp. Results showed effective antiviral
      activity against CyHV-3 pre- and post-infection. The 50% lethal concentration
      (LC50 ) of extract was higher than 5 mg/ml. The 50% effective dose (ED50 ) was
      0.99 mg/ml, 0.78 mg/ml, 0.75 mg/ml and 0.71 mg/ml at 1, 2, 3 and 4 hr pre
      infection, respectively. The ED50 from post-infection tests was 2.05 mg/ml and
      2.34 mg/ml at 0 and 24 hr, respectively. These results demonstrated that crude
      extract expressed antiviral activity against CyHV-3 and can be applied as a
      therapeutic agent in common carp and koi aquaculture.

PMID- 29468850
TI  - An unusual clinical presentation of myxoid dermatofibrosarcoma protuberans with a
      prominent vasculature: A potential pitfall in the diagnosis of myxoid soft tissue
      tumors.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue tumor that arises
      primarily on the trunk and extremities but seldom on the scalp. Several variants
      of DFSP have been described, including myxoid DFSP. Although typical DFSP may
      have focally myxoid areas, myxoid DFSP, in which most of the stroma is myxoid, is
      rare and can pose diagnostic challenges. Here, we report a case of myxoid DFSP
      with an unusual clinical presentation that could have been mistaken for a lipoma.
      Additionally, the myxoid DFSP displayed prominent vasculature in a myxoid stroma,
      which could have been mistaken for a myxoid liposarcoma.

PMID- 29468851
TI  - Isolates from Alpinia officinarum Hance attenuate LPS-induced inflammation in
      HepG2: Evidence from in silico and in vitro studies.
AB  - In an attempt to connect the legacy of centuries of invaluable knowledge from
      traditional medicine and the current understanding to the molecular mechanism of
      diseases, we took the advantage of the emergence of in silico screening as a
      promising tool for identification of potential leads from libraries of natural
      products. Traditional Chinese Medicine database was subjected to structure based
      virtual screening for identification of anti-inflammatory compounds using the 3D
      crystal structure of p38 alpha mitogen activated protein kinase. The molecular
      docking studies revealed the potential activity of several classes of compounds
      known to be the constituents of the rhizomes of Alpinia officinarum Hance (Lesser
      galangal). Five compounds, galangin, kaempferide, isorhamnetin, and two
      diarylheptanoids, were isolated from the rhizomes of the plant using vacuum
      liquid chromatography and flash chromatography techniques. The anti-inflammatory
      activity of these compounds was investigated on HepG2 cells stimulated by
      lipopolysaccharide. The latter induced the gene expression of proinflammatory
      cytokines; interleukin-1beta, interleukin-6, tumor necrosis factor alpha.
      Addition of the 5 isolated compounds downregulated this increased gene expression
      in a dose dependent manner. Thus, these results indicate that the isolated
      compounds from A. officinarum could be used as a beneficial source for preventing
      and treating inflammatory diseases.

PMID- 29468852
TI  - Dye-Incorporated Polynaphthalenediimide Acceptor for Additive-Free High
      Performance All-Polymer Solar Cells.
AB  - All-polymer solar cells (all-PSCs) can offer unique advantages for applications
      in flexible devices, and naphthalene diimide (NDI)-based polymer acceptors are
      the widely used polymer acceptors. However, their power conversion efficiency
      (PCE) still lags behind that of state-of-the-art polymer solar cells, due to low
      light absorption, suboptimal energy levels and the strong aggregation of the NDI
      based polymer acceptor. Herein, a rhodanine-based dye molecule was introduced
      into the NDI-based polymer acceptor by simple random copolymerization and showed
      an improved light absorption coefficient, an up-shifted lowest unoccupied
      molecular orbital level and reduced crystallization. Consequently, additive-free
      all-PSCs demonstrated a high PCE of 8.13 %, which is one of the highest
      performance characteristics reported for all-PSCs to date. These results indicate
      that incorporating a dye into the n-type polymer gives insight into the precise
      design of high-performance polymer acceptors for all-PSCs.

PMID- 29468853
TI  - The effect of hydroxyapatite nanoparticles on adipogenic differentiation of human
      mesenchymal stem cells.
AB  - Due to its excellent biocompatibility, nanosized hydroxyapatite (nHA) has drawn
      much attention for various applications in biomedical fields. There are growing
      concerns about its biosecurity; however, little is known about its effects on
      adipogenesis. In the present study, nHA with three different sizes were
      synthesized, and the in vitro effects of nHA on cell proliferation and adipogenic
      differentiation of human mesenchymal stem cells (hMSCs) were investigated. The
      results clearly show that nHA does not affect the cell viability, the lipids
      droplets formation, triglyceride (TG) synthesis, and the expression of adipogenic
      marker genes/proteins of hMSCs at concentrations lower than 50 MUg/mL. It is
      concluded that the adipogenic differentiation potential of hMSCs is not affected
      by nHA at noncytotoxic concentrations. These will provide a reference for the
      applications of nHA in biomedical fields. (c) 2018 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 106A: 1822-1831, 2018.

PMID- 29468854
TI  - Differential effects of oxycodone and venlafaxine on resting state functional
      connectivity-A randomized placebo-controlled magnetic resonance imaging study.
AB  - AIM: Different mechanisms may be involved in the antinociceptive effects of
      oxycodone (opioid) and venlafaxine (serotonin-norepinephrine reuptake inhibitor),
      and the aim of this study was to investigate the effect of these drugs on brain
      functional connectivity. METHODS: Resting state functional magnetic resonance
      imaging was acquired in 20 healthy volunteers before and after a 5-day treatment
      with oxycodone, venlafaxine, or placebo in a randomized, double-blind, crossover
      study. Functional connectivity analyses were performed between four predefined
      seeds (dorsal anterior cingulate cortex, rostral anterior cingulate cortex,
      posterior insula, and prefrontal cortex), and the whole brain. RESULTS: The
      overall interpretation was that there were differences between the effects of
      oxycodone and venlafaxine on functional connectivity. Oxycodone mainly showed
      decreased functional connectivity between limbic structures and to supralimbic
      areas (all P < 0.05). Venlafaxine also showed decreased functional connectivity
      between limbic structures and to supralimbic areas, but increased functional
      connectivity to structures in the midbrain and brain stem was also found (all P <
      0.05). CONCLUSIONS: Oxycodone and venlafaxine showed differential effects on
      resting-state functional connectivity as compared to placebo. This supports that
      the two drugs exert different mechanisms, and that the drugs in combination may
      exert additive effects and could potentially improve pain therapy.

PMID- 29468855
TI  - Major clinical research advances in gynecologic cancer in 2017.
AB  - In 2017, 10 topics were selected as major clinical research advances in
      gynecologic oncology. For cervical cancer, efficacy and safety analysis results
      of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced
      dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials
      of pembrolizumab, a monoclonal antibody that blocks the interaction between
      programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored
      surveillance programs for gynecologic cancer related with Lynch syndrome and
      update on sentinel lymph node mapping were reviewed for uterine corpus cancer.
      For ovarian cancer, 5 topics were selected including poly(ADP-ribose) polymerases
      inhibitors and immunotherapy. The other potential practice changers covered in
      this review were lymphadenectomy in advanced disease, secondary cytoreductive
      surgery in recurrent disease, weekly dose-dense regimen for first-line
      chemotherapy, incorporation of bevacizumab maintenance in platinum-sensitive
      recurrent disease, and effect of platinum-free interval prolongation. Conflicting
      opinions of academic societies on periodic pelvic examination were introduced in
      conjunction with relevant literature review. For the field of radiation oncology,
      results of 2 big trials, The Postoperative Radiation Therapy in Endometrial
      Carcinoma-3 and Gynecologic Oncology Group-258, for endometrial cancer and recent
      advance in high-dose-rate brachytherapy for cervical cancer were reported. Topics
      for breast cancer covered adjuvant capecitabine after preoperative chemotherapy,
      adjuvant pertuzumab and trastuzumab in early human epidermal growth factor
      receptor 2-positive disease, olaparib for metastatic cancer in patients with a
      germline BRCA mutation, 20-year risks of recurrence after stopping endocrine
      therapy at 5 years, and contemporary hormonal contraception and the risk of
      breast cancer.

PMID- 29468857
TI  - The 5th Biennial Meeting of the Asian Society of Gynecologic Oncology, November
      30th to December 2nd, 2017.

PMID- 29468856
TI  - Chemoresistance in ovarian cancer: exploiting cancer stem cell metabolism.
AB  - Ovarian cancer is most deadly gynecologic malignancies worldwide. Chemotherapy is
      the mainstay treatment for ovarian cancer. Despite the initial response is
      promising, frequent recurrence in patients with advanced diseases remains a
      therapeutic challenge. Thus, understanding the biology of chemoresistance is of
      great importance to overcome this challenge and will conceivably benefit the
      survival of ovarian cancer patients. Although mechanisms underlying the
      development of chemoresistance are still ambiguous, accumulating evidence has
      supported an integral role of cancer stem cells (CSCs) in recurrence following
      chemotherapy. Recently, tumor metabolism has gained interest as a reason of
      chemoresistance in tumors and chemotherapeutic drugs in combination with
      metabolism targeting approaches has been found promising in overcoming
      therapeutic resistance. In this review, we will summarize recent studies on CSCs
      and metabolism in ovarian cancer and discuss possible role of CSCs metabolism in
      chemoresistance.

PMID- 29468858
TI  - Treating the emotional and motivational inhibition of highly gifted
      underachievers with music psychotherapy: Meta-analysis of an evaluation study
      based on a sequential design.
AB  - The psychological and neuropsychological characteristics of gifted children
      andadolescents are analysed, as well as the emotional and behavioural risks
      linkedto this condition.A prospective follow-up study of N=93 highly gifted
      students suffering fromschool failure at the beginning of adolescence was
      implemented. They weretreated with an integrated form of music psychotherapy and
      verbal psychotherapyin 5 separate groups. The methodology of treatment combined
      active musicalimprovisation with the writing of stories or the production of
      drawings undermusical induction, followed by verbal elaboration in the cognitive
      psychodynamicpsychotherapeutic tradition.The evaluation was based on a mixed
      methods design, combining psychometricscales, projective tests and expressive
      tests. Comparative pretest-posttest,correlational and multidimensional analyses
      were computed, using non-parametricstatistical procedures adapted to small
      samples and data belonging to a mixedlevel of measurement. We present a meta
      analysis of the confirmatory results in5 subgroups.There was a significant
      increase in the capacity of concentration, the capacityof imaginary and symbolic
      elaboration, the pictorial and literary creativity,self-esteem, the quality of
      coping strategies, as well as in school marks. Therewas a significant decrease in
      defensive functioning and in embitterment andresignation. The latent dimensions
      extracted with Optimal Scaling proceduresfrom the correlational matrixes of the
      Delta values of TAT and TSD-Z weremeaningful at the light of the state-of-the
      arts.The results of the study confirm a prior theoretical modelization coming out
      ofthe preparatory stage of the research project. They are interpreted at the
      light ofrecent findings in developmental and clinical psychology of adolescence
      and theyopen many tracks for future research.

PMID- 29468859
TI  - [In process]
AB  - Over a short period of one month we undertook a systematic review of
      allmedications of our residents in the nursing home. Prior to this we examined
      thepatients with great care and where necessary, laboratory tests or other
      furtherinvestigations took place. By the end of this procedure, we analysed
      themedications prescribed and on the recommendations of the program Stopp
      andStart, several adaptations were done. In summary, some medications
      increased,mainly for osteoporosis prevention and some other could be reduced,
      mainlythe psychotropic drugs. A systematic review for patients in nursing homes,
      twicea year seems sufficient for the adaptations of chronically used
      medications.Psycho-Geriatric patients - Medications - Stopp and Start programme.

PMID- 29468860
TI  - [Jewish Doctors in Luxembourg: A misunderstood minority].
AB  - After an outline on the hypocrisy of the Catholic Church towards jewish
      doctors,the author list some arguments to explain why Jewish doctors were that
      soughtafter. He then concentrates on the situation in Luxembourg - on
      indigenousdoctors and migrants, finishing with a parallel between asylum seekers
      fromyesterday and today.

PMID- 29468861
TI  - Spine surgery under general anaesthesia complicated by Wernicke's encephalopathy
      in previously asymptomatic patient.
AB  - Wernicke's encephalopathy (WE) is a very rare complication of
      surgicalintervention, especially among patients with no liver dysfunction and no
      history ofalcohol abuse. In a surgical setting, Wernicke's syndrome was mostly
      associatedwith abdominal surgery (bariatric, e.g. gastric bypass, splenectomy)
      but there areno papers in the literature dealing with such a complication among
      spine patients.

PMID- 29468862
TI  - A Retrospective Study looking at Admissions Characteristics of Patients admitted
      to an Oncology Ward in Luxembourg.
AB  - Our study set out to monitor all admissions admitted to an oncology ward overa
      period of 60 days between 20/10/14 and 18/12/14. We wanted to analyse thereasons
      for admission, in order to identify treatment related complications andother
      preventable causes for inpatient admission.

PMID- 29468863
TI  - [In process].
AB  - Benzodiazepine hypnotics bear a higher risk of high dose dependence
      thanbenzodiazepine anxiolytics, according to a recent study in Luxemburg.
      Thisarticle summarizes the main indications of these molecules and the
      currenttreatment recommendations. It provides an overview of public health
      actions ofthe past and the future to reduce their excessive consumption.

PMID- 29468864
TI  - Case Report: Primary Spinal Lymphoma.
AB  - This is the report on the case of a 74 year old male patient who was admitted to
      hospital emergency because of a distended bladder, which was detected on an MRI.
      This MRI was performed because of an acute paralysis of the patient's left leg.
      After various examinations we could conclude that the patient's neurological
      symptoms were not due to metastases of a solid tumour as we expected, but to a
      primary spinal diffuse B-cell lymphoma. The central nervous system, and
      especially the spinal cord, are an extremely rare location for primary B-Cell
      lymphoma.

PMID- 29468865
TI  - Iron Hydroxide-Modified Nickel Hydroxylphosphate Single-Wall Nanotubes as
      Efficient Electrocatalysts for Oxygen Evolution Reactions.
AB  - Development of efficient electrocatalysts for oxygen evolution reaction (OER) is
      of great significance for future renewable energy applications. Herein, efficient
      OER electrocatalysts based on iron hydroxide-modified nickel hydroxylphosphate
      (NiPO/Fe(OH) x) single-wall nanotubes (SWNTs) have been prepared by a facile
      stepwise surfactant-free solvothermal strategy, which possess diameters of about
      6 nm and lengths of about several micrometers. Benefiting from the synergistic
      effect between iron hydroxides and NiPO SWNTs, the as-prepared NiPO/Fe(OH) x
      SWNTs exhibit higher OER activity than primary NiPO SWNTs. Furthermore, the OER
      activity with different Fe contents displays a volcano-type shape, and the
      optimized NiPO/Fe(OH) x SWNTs present excellent activity with a low overpotential
      of 248 mV to deliver a current density of 10 mA cm-2 and 323 mV to achieve a
      large current density of 100 mA cm-2, as well as a remarkably low Tafel slope of
      45.4 mV dec-1 in 1 M KOH electrolyte. The present work provides valuable insights
      to improve the OER performance by rational surface modification.

PMID- 29468866
TI  - Quantifying the Degree of Aggregation from Fluorescent Dye-Conjugated DNA Probe
      by Single Molecule Photobleaching Technology for the Ultrasensitive Detection of
      Adenosine.
AB  - In this work, we demonstrated a single molecule photobleaching-based strategy for
      the ultrasensitive detection of adenosine. A modified split aptamer was designed
      to specifically recognize individual adenosine molecules in solution. The
      specific binding of dye-labeled short strand DNA probes onto the elongated
      aptamer strand in the presence of adenosine resulted in a concentration-dependent
      self-aggregation process. The degree-of-aggregation (DOA) of the short DNA probes
      on the elongated aptamer strand could then be accurately determined based on the
      single molecule photobleaching measurement. Through statistically analyzing the
      DOA under different target concentrations, a well-defined curvilinear
      relationship between the DOA and target molecule concentration (e.g., adenosine)
      was established. The limit-of-detection (LOD) is down to 44.5 pM, which is lower
      than those recently reported results with fluorescence-based analysis. Owing to
      the high sensitivity and excellent selectivity, the sensing strategy described
      herein would find broad applications in biomolecule analysis under complicated
      surroundings.

PMID- 29468867
TI  - Simple and Sensitive Method for Determination of Protein Kinase Activity Based on
      Surface Charge Change of Peptide-Modified Gold Nanoparticles As Substrates.
AB  - Protein tyrosine kinases play a pivotal role in intracellular signal transduction
      pathways and oncogenic transformation. It is necessary to develop a simple, cost
      effective, and sensitive kinase assay for study of protein kinases and discovery
      of kinase-target drugs. In this paper, we present a simple and sensitive method
      for homogeneous detection of protein kinase activity and screening of inhibitor
      by measuring surface charge change on the peptide-modified gold nanoparticles
      (GNPs) as kinase substrates. In this assay, Abl (Abelson murine leukemia viral
      oncogene) kinase was used as a model. In the presence of Abl kinase and ATP, the
      surface negative charge on GNPs significantly increases due to phosphorylation of
      the peptide-modified GNPs. The surface charge on the peptide-modified GNPs was
      measured by zeta potential analyzer. Under the optimum conditions, the zeta
      potential on the peptide-modified GNPs was linearly dependent on Abl kinase
      concentration, the linear range was from 1 to 40 nM and the detection limit was 1
      nM. This method was used to evaluate the inhibition efficiency of inhibitors, and
      the obtained IC50 values were well in agreement with the results reported in the
      references. Furthermore, this method was successfully applied to determine Abl
      kinase activity in the cell lysates. Compared to current methods, this new method
      shows simplicity, short analysis time, high sensitivity, and will become a
      promising platform for kinase-related fundamental research and inhibitor
      screening.

PMID- 29468868
TI  - B-Site Cation-Ordered Double-Perovskite Oxide as an Outstanding Electrode
      Material for Supercapacitive Energy Storage Based on the Anion Intercalation
      Mechanism.
AB  - Perovskite oxides are highly promising electrodes for oxygen-ion-intercalation
      type supercapacitors owing to their high oxygen vacancy concentration, oxygen
      diffusion rate, and tap density. Based on the anion intercalation mechanism, the
      capacitance is contributed by surface redox reactions and oxygen ion
      intercalation in the bulk materials. A high concentration of oxygen vacancies is
      needed because it is the main charge carrier. In this study, we propose a B-site
      cation-ordered Ba2Bi0.1Sc0.2Co1.7O6-delta as an electrode material with an
      extremely high oxygen vacancy concentration and oxygen diffusion rate. A maximum
      capacitance of 1050 F g-1 was achieved, and a high capacitance of 780 F g-1 was
      maintained even after 3000 charge-discharge cycles at a current density of 1 A g
      1 with an aqueous alkaline solution (6 M KOH) electrolyte, indicating an
      excellent cycling stability. In addition, the specific volumetric capacitance of
      Ba2Bi0.1Sc0.2Co1.7O6-delta reaches up to 2549.4 F cm-3 based on the dense
      construction and high tap density (3.2 g cm-3). In addition, an asymmetric
      supercapacitor was constructed using activated carbon as a negative electrode,
      and it displayed the highest specific energy density of 70 Wh kg-1 at the power
      density of 787 W kg-1 in this study.

PMID- 29468869
TI  - Nonvolatile Electric Double-Layer Transistor Memory Devices Embedded with Au
      Nanoparticles.
AB  - We present nonvolatile transistor memory devices that rely on the formation of
      electric double layer (EDL) at the semiconductor-electrolyte interface. The two
      critical functional components of the devices are the ion gel electrolyte and
      gold nanoparticles (NPs). The ion gel electrolyte contains ionic species for EDL
      formation that allow inducing charges in the semiconductor-electrolyte interface.
      The gold NPs inserted between the ion gel and the channel layer serve as trapping
      sites to the induced charges to store the electrical input signals. Two different
      types of gold NPs were used: one prepared using direct thermal evaporation and
      the other prepared using a colloidal process. The organic ligands attached onto
      the colloidal gold NPs prevented the escape of the trapped charges from the
      particles and thus enhanced the retention characteristics of the
      programmed/erased signals. The low-voltage-driven EDL formation resulted in a
      programmed/erased memory signal ratio larger than 103 from the nonvolatile indium
      gallium-zinc oxide transistor memory devices at voltages below 10 V, which could
      be held for >105 s. The utility of the electrolytes to operate memory devices
      demonstrated herein should provide an alternative strategy to realize cheap,
      portable electronic devices powered with thin-film batteries.

PMID- 29468870
TI  - Phase-Change Partitions for Thermal Automation of Multistep Reactions.
AB  - Medical diagnostics and basic research in low-resource settings require automated
      reactions to be controlled in a simple, portable manner. Here, we present a novel
      platform that enables simple automation of multistep reactions to facilitate
      robust, hands-free assay operation without complex microfluidics or
      paperfluidics. We separate reagent zones in a conventional PCR tube via solid
      layers of purified higher alkanes. Reagents can be mixed on demand by simply
      raising the temperature above the melting point of the alkane partition that
      separates the two zones. We partitioned various reagents to enable hands-free
      thermally automated isothermal nucleic acid amplification, heavy metal ion
      detection, and beta-lactamase detection with tandem antibiotic specificity
      characterization. We anticipate that this phase-change partition platform will
      find broad application in clinical diagnostics at the point-of-care and in low
      resource settings.

PMID- 29468871
TI  - Peptide Probe for Multiwalled Carbon Nanotubes: Electrophoretic Assessment of the
      Binding Interface and Evaluation of Surface Functionalization.
AB  - Noncovalent interactions of peptides and proteins with carbon nanotubes play a
      key role in sensing, dispersion, and biocompatibility. Advances in these areas
      require that the forces which contribute to physical adsorption are understood in
      order that the carbon nanotubes present a degree of functionalization appropriate
      to the desired application. Affinity analyses of peptides are employed to
      evaluate the role of tryptophan and arginine residues in physical adsorption to
      carboxylated multiwalled carbon nanotubes. Peptides containing arginine and
      tryptophan, WR(W) n, are used with affinity capillary electrophoresis to identify
      factors that lead to the formation of peptide-carbon nanotube complexes. The
      effects of changing the amino acid composition and residue length are evaluated
      by measuring dissociation constants. Electrostatic interactions contribute
      significantly to complexation, with the strongest interaction observed using the
      peptide WRWWWW and carboxylated carbon nanotube. Stronger interaction is observed
      when the tryptophan content is successively increased as follows: WR(W)4 > WR(W)3
      > WR(W)2 > WRW > WR. However, as observed with polytryptophan (W5, W4, W3, and
      W2), removing the arginine residue significantly reduces the interaction with
      carbon nanotubes. Increasing the arginine content to WRWWRW does not improve
      binding, whereas replacing the arginine residue in WRWWWW with lysine (WKWWWW)
      reveals that lysine also contributes to surface adsorption, but not as
      effectively as arginine. These observations are used to guide a search of the
      primary sequence of lysozyme to identify short regions in the peptide that
      contain a single cationic residue and two aromatic residues. One candidate
      peptide sequence (WMCLAKW) from this search is analyzed by capillary
      electrophoresis. The dissociation constant of carboxylated multiwalled carbon
      nanotubes is measured for the peptide, WMCLAKW, to demonstrate the utility of
      affinity capillary electrophoresis analysis.

PMID- 29468873
TI  - Quantitative Analysis of the Incorporation Behaviors of Sr and Ti Atoms During
      the Atomic Layer Deposition of SrTiO3 Thin Films.
AB  - The atomic layer deposition (ALD) of multication oxide films is complicated
      because the deposition behaviors of the component oxides are not independent of
      one another. In this study, the Ti and Sr atom incorporation behaviors during the
      ALD of SrTiO3 films were quantitatively examined via the carefully designed ALD
      process sequences. H2O and O3 were adopted as the oxygen sources of the SrO
      subcycles, whereas only O3 was used for the TiO2 ALD subcycles. Apart from the
      general conjecture on the roles of the different types of oxygen sources, the
      oxygen source that was adopted for the subcycles of the other component oxide had
      almost complete control of the metal atom incorporation behaviors. This means
      that the first half-cycle of ALD played a dominant role in determining the metal
      incorporation rate, which revealed the critical role of the steric hindrance
      effect during the metal precursor injection for the ALD rate. O3 had almost
      doubled its reactivity toward the Ti and Sr precursors compared with H2O.
      Although these are the expected results from the common knowledge on ALD, the
      quantitative analysis of the incorporation behaviors of each metal atom provided
      insightful viewpoints for the ALD process of this technically important oxide
      material. Furthermore, the SrTiO3 films with a bulk dielectric constant as high
      as 236 were obtained by the Ru-SrTiO3-RuO2 capacitor structure.

PMID- 29468872
TI  - Quest for Efficacious Next-Generation Taxoid Anticancer Agents and Their Tumor
      Targeted Delivery.
AB  - Paclitaxel and docetaxel are among the most widely used chemotherapeutic drugs
      against various types of cancer. However, these drugs cause undesirable side
      effects as well as drug resistance. Therefore, it is essential to develop next
      generation taxoid anticancer agents with better pharmacological properties and
      improved activity especially against drug-resistant and metastatic cancers. The
      SAR studies by the authors have led to the development of numerous highly potent
      novel second- and third-generation taxoids with systematic modifications at the C
      2, C-10, and C-3' positions. The third-generation taxoids showed virtually no
      difference in potency against drug-resistant and drug-sensitive cell lines. Some
      of the next-generation taxoids also exhibited excellent potency against cancer
      stem cells. This account summarizes concisely investigations into taxoids over 25
      years based on a strong quest for the discovery and development of efficacious
      next-generation taxoids. Discussed herein are SAR studies on different types of
      taxoids, a common pharmacophore proposal for microtubule-stabilizing anticancer
      agents and its interesting history, the identification of the paclitaxel binding
      site and its bioactive conformation, characteristics of the next-generation
      taxoids in cancer cell biology, including new aspects of their mechanism of
      action, and the highly efficacious tumor-targeted drug delivery of potent next
      generation taxoids.

PMID- 29468874
TI  - Shape Engineering Boosts Magnetic Mesoporous Silica Nanoparticle-Based Isolation
      and Detection of Circulating Tumor Cells.
AB  - Magnetic mesoporous silica nanoparticles (M-MSNs) are attractive candidates for
      the immunomagnetic isolation and detection of circulating tumor cells (CTCs).
      Understanding of the interactions between the effects of the shape of M-MSNs and
      CTCs is crucial to maximize the binding capacity and capture efficiency as well
      as to facilitate the sensitivity and efficiency of detection. In this work,
      fluorescent M-MSNs were rationally designed with sphere and rod morphologies
      while retaining their robust fluorescence and uniform surface functionality.
      After conjugation with the antibody of epithelial cell adhesion molecule (EpCAM),
      both of the differently shaped M-MSNs-EpCAM obtained achieved efficient
      enrichment of CTCs and fluorescent-based detection. Importantly, rodlike M-MSNs
      exhibited faster immunomagnetic isolation as well as better performance in the
      isolation and detection of CTCs in spiked cells and real clinical blood samples
      than those of their spherelike counterparts. Our results showed that shape
      engineering contributes positively toward immunomagnetic isolation, which might
      open new avenues to the rational design of magnetic-fluorescent nanoprobes for
      the sensitive and efficient isolation and detection of CTCs.

PMID- 29468875
TI  - Protein Plasticity and Peptide Editing in the MHC I Antigen Processing Pathway.

PMID- 29468876
TI  - Janus Nanoparticles for Improved Dentin Bonding.
AB  - The amphiphilic monomer 2-hydroxyethyl methacrylate (HEMA) is widely used in
      dental adhesives as a priming component, especially for dentin bonding. It
      behaves as a compatibilizer between hydrophilic and hydrophobic components and
      stabilizes the multicomponent adhesive system. However, there are several
      drawbacks associated with using HEMA, such as water retention within the adhesive
      layer, hydrolysis in oral environments, and cytotoxicity. These drawbacks lead to
      the failure of tooth restoration and represent a heavy medical burden. Thus, it
      is imperative to find a new compatibilizer to substitute for HEMA. Because of
      their superior compatibilization capabilities as functional solid surfactants,
      amphiphilic Janus particles are chosen as candidates for an alternative to HEMA
      in dental adhesives. Reactive amphiphilic Janus nanoparticles are synthesized by
      selectively etching and modifying at the interface of a Pickering emulsion. This
      approach could be extended to the synthesis of a series of other Janus
      nanoparticles. The Janus nanoparticles were verified to be better for the
      reduction of the phase separation and stabilization of dentin adhesives than
      HEMA. It is also demonstrated that these reactive Janus nanoparticles can
      strongly enhance the dentin bonding interface without cytotoxicity. It is clearly
      illustrated by this study that Janus nanoparticles may be promising materials to
      substitute for HEMA in dental adhesives.

PMID- 29468877
TI  - Complete Biotransformation of Protopanaxadiol-Type Ginsenosides to 20- O-beta
      Glucopyranosyl-20( S)-protopanaxadiol Using a Novel and Thermostable beta
      Glucosidase.
AB  - The ginsenoside 20- O-beta-glucopyranosyl-20( S)-protopanaxadiol, compound K, has
      attracted much attention in functional food, traditional medicine, and cosmetic
      industries because of diverse pharmaceutical activities. The effective production
      of compound K from ginseng extracts has been required. However, an enzyme capable
      of completely converting all protopanaxadiol (PPD)-type ginsenosides to compound
      K has not been reported until now. In this study, unlike other enzymes, beta
      glucosidase from Caldicellulosiruptor bescii was able to hydrolyze sugar moieties
      such as l-arabinofuranose as well as d-glucose and l-arabinopyranose as the C-20
      outer sugar in ginsenosides. Thus, ginsenoside Rc containing l-arabinofuranose
      can be converted to compound K by only this enzyme. Under the optimized reaction
      conditions, the enzyme completely converted PPD-type ginsenosides in ginseng
      extracts to compound K with the highest productivity among the reported results.
      This is the first report of the enzyme capable of completely converting all PPD
      type ginsenosides into compound K.

PMID- 29468878
TI  - Identification of a Novel Esterase from Marine Environmental Genomic DNA
      Libraries and Its Application in Production of Free All- trans-Astaxanthin.
AB  - Astaxanthin is a pigment with various functions. Free astaxanthin is obtained
      mainly through saponification methods, which could result in many byproducts.
      Enzymatic methods using lipases have been used in a few cases, while there are no
      reports on the use of esterases for the production of free astaxanthin. Herein we
      present the screening and identification of a novel esterase (Est3-14) from a
      marine mud metagenomic library. Est3-14 is pH-sensitive and keeps good stability
      in alkaline buffers (residual activity 94%, pH 8.0, 4  degrees C, and 36 h).
      Meanwhile, Est3-14 keeps a good stability in the medium temperature condition
      (residual activity 56.7%, pH 8.0, 40  degrees C, and 84 h). Est3-14 displayed
      high hydrolysis activity to prepare free all- trans-astaxanthin in biphasic
      systems. Furthermore, under optimal conditions (0.5 mL ethanol, 6 mL 0.1 M Tris
      HCl buffer, pH 8.0, 0.5% (w/v) H. pluvialis oil, 40  degrees C), the hydrolytic
      conversion ratio was 99.3% after 36 h.

PMID- 29468879
TI  - A Bioluminescent Probe for Imaging Endogenous Peroxynitrite in Living Cells and
      Mice.
AB  - Peroxynitrite (ONOO-), an extremely reactive nitrogen species (RNS), is
      implicated in diverse pathophysiological conditions, including cancer,
      neurodegenerative diseases, and inflammation. Sensing and imaging of ONOO- in
      living systems remains challenging due to the high autofluorescence and the
      limited light penetration depth. In this work, we developed a bioluminescent
      probe BP-PN, based on luciferase-luciferin pairs and the ONOO--responded group
      alpha-ketoamide, for highly sensitive detection and imaging of endogenous ONOO-
      in living cells and mice for the first time. Attributed to the BL without
      external excitation, the probe BP-PN exhibits a high signal-to-noise ratio with
      relatively low autofluorescence. Furthermore, we examine the application of the
      probe BP-PN using the mice model of inflammation, and BP-PN shows high
      sensitivity for imaging endogenous ONOO- in inflamed mice. This newly developed
      bioluminescent probe would be a potentially useful tool for in vivo imaging of
      ONOO- in wider physiological and pathological processes.

PMID- 29468880
TI  - Soft/Hard-Coupled Amphiphilic Polymer Nanospheres for Water Lubrication.
AB  - Amphiphilic polymer nanospheres of poly(3-sulfopropyl methacrylate potassium salt
      co-styrene) [P(SPMA- co-St)] were prepared by a simple soap-free emulsion
      polymerization method and used as efficient water lubrication additives to
      enhance the antiwear behaviors of the Ti6Al4V alloy. The monodisperse and
      flexible P(SPMA- co-St) bicomponent copolymer nanospheres were synthesized with a
      controllable manner by adjusting the mass fraction ratio of the monomers, with
      the hydrophobic polystyrene (PSt) as the hard skeletal carrier component and the
      hydrophilic PSPMA with a hydration layer structure as the soft lubrication layer
      in the course of friction. The influences of the monomer concentration, the
      copolymer nanosphere additive content, the load, and the frequency of the
      friction conditions on their tribological properties were studied in detail, and
      a probable antiwear mechanism of the soft/hard-coupled copolymer nanospheres
      under water lubrication was also proposed. The results show that compared with
      pure PSt, the P(SPMA- co-St) polymer nanospheres exhibited better antiwear
      property as an additive for water lubrication, and the friction coefficient and
      the wear volume first decreased and then increased with the increase of the SPMA
      content, indicating that the hydrophilic SPMA has a significant effect on
      lubrication properties owing to its hydration performance. Furthermore, with the
      increase of polymer nanosphere concentration, the friction coefficient and wear
      amount also decreased to a stable and low value at a saturation concentration of
      1 wt %. The flexible polymer nanospheres with a hydrophilic soft SPMA shell and a
      rigid PSt core exhibited good friction-reduction and antiwear performance as
      lubrication additives, indicating their promising and potential applications in
      water lubrication and biological lubrication.

PMID- 29468881
TI  - Rhodium-Catalyzed Relay Carbenoid Functionalization of Aromatic C-H Bonds toward
      Fused Heteroarenes.
AB  - A rhodium-catalyzed annulation between ethyl benzimidates and alpha- aroyl sulfur
      ylides was developed, affording a series of pyrano[4,3,2-ij]isoquinoline
      derivatives in moderate to good yields with good functional group compatibility.
      The procedure featured dual ortho-C-H functionalization and dual cyclization in
      one pot. The optoelectronic properties of those fused heteroarenes were tested by
      UV/vis and fluorescence spectrometers.

PMID- 29468882
TI  - Coupling a Germanium Hut Wire Hole Quantum Dot to a Superconducting Microwave
      Resonator.
AB  - Realizing a strong coupling between spin and resonator is an important issue for
      scalable quantum computation in semiconductor systems. Benefiting from the
      advantages of a strong spin-orbit coupling strength and long coherence time, the
      Ge hut wire, which is proposed to be site-controlled grown for scalability, is
      considered to be a promising candidate to achieve this goal. Here we present a
      hybrid architecture in which an on-chip superconducting microwave resonator is
      coupled to the holes in a Ge quantum dot. The charge stability diagram can be
      obtained from the amplitude and phase responses of the resonator independently
      from the DC transport measurement. Furthermore, we estimate the hole-resonator
      coupling rate of gc/2pi = 148 MHz in the single quantum dot-resonator system and
      estimate the spin-resonator coupling rate gs/2pi to be in the range 2-4 MHz. We
      anticipate that strong coupling between hole spins and microwave photons in a Ge
      hut wire is feasible with optimized schemes in the future.

PMID- 29468883
TI  - Complicated war trauma and care of the wounded - the Israeli experience in
      medical care and humanitarian support of Syrian refugees.

PMID- 29468884
TI  - Borrowing Benefits: Group Treatment With Clinical Emotional Freedom Techniques Is
      Associated With Simultaneous Reductions in Posttraumatic Stress Disorder,
      Anxiety, and Depression Symptoms.
AB  - Clinical Emotional Freedom Techniques (EFT) is an evidence-based treatment for
      depression and anxiety. The current study sought to elucidate the relationship
      between posttraumatic stress disorder (PTSD), depression, and anxiety in a
      nonclinical population. The sample (N = 81) comprised participants at five 2-day
      EFT workshops. All groups used an EFT protocol called Borrowing Benefits, in
      which the group facilitator works with a single client while other participants
      self-apply EFT. Participants were assessed on 9 specific conditions as well as on
      the breadth (Positive Symptom Total [PST]) and depth (General Symptom Index
      [GSI]) of psychological distress. Physical pain and addictive cravings were also
      assessed. Significant reductions were observed in all measures (P < .03).
      Associations between PST, GSI, and PTSD were significant (P < .026). Participants
      maintained all gains at 6-month follow-up (P < .02) with the exception of the
      Hostility subscale, while Cohen's d = 0.54 indicated a moderate treatment effect
      for PTSD. The relationship between psychological and physiological conditions
      identified in this study is consistent with that found in other studies. Group
      treatment is cost-effective and efficient, and the efficacy of EFT in groups
      indicates the utility of the Borrowing Benefits technique.

PMID- 29468885
TI  - Allelopathic effect of the ethanol extract and fractions of the aerial parts of
      Lippia alba (Verbenaceae).
AB  - Lippia alba, belonging to the Verbenaceae family, is one of the most commonly
      utilized medicinal plants in folk medicine. The allelopathic activity was
      assessed using seeds of Lactuca sativa (lettuce) and Allium cepa (onion) by
      assessing the growth of the radicle and hypocotyl. The tests showed allelopathic
      efficiency in inhibiting the growth of lettuce and onion seeds. The best results
      for allelopathic activity were presented by the dichloromethane (DCM) fraction of
      the fresh plant, which inhibited radicle (23.04-100% lettuce and 64.17-66.36%
      onion) and hypocotyl (16.77-100% lettuce and 65.10-69.43% onion) formation, and
      as well as the DCM fraction of the dry plant, which also inhibited radicle (30.74
      82.83% lettuce and 63.50-93.67% onion) and hypocotyl (24.12-70% lettuce and 69.07
      79.95% onion) formation. Based on these results, it was found that the aerial
      parts of L. alba are rich in bioactive substances, suggesting the possibility of
      using of L. alba as a natural herbicide.

PMID- 29468887
TI  - Managing behavioral and psychological symptoms in Chinese elderly with dementia
      via group-based music intervention: A cluster randomized controlled trial.
AB  - The present study aimed to evaluate the effects of a group music intervention in
      managing behavioral and psychological symptoms in Chinese elderly with dementia.
      This cluster randomized trial recruited 73 elderly participants with moderate
      dementia from 10 elderly residential homes and assigned them to the intervention
      ( n = 40) and control ( n = 33) group. The intervention included 16 half-hour
      sessions of music intervention with multi-sensory components over eight weeks and
      control group received standard care. Participants' levels of subjective moods
      and neuropsychiatric symptoms such as agitation, aberrant motor behaviors,
      dysphoria, and irritability were assessed at baseline, the 2nd, 4th, 6th, and the
      end of the intervention. Controlling for baseline outcomes, latent growth
      modeling revealed significant intervention effects for agitation ( B = -1.03, SE
      = 0.30, p < 0.01), aberrant motor behavior ( B = -1.80, SE = 0.66, p < 0.01), and
      dysphoria ( B = -0.79, SE = 0.36, p < 0.05), with the intervention group showing
      improvements compared to no substantial changes in the control group. There were
      no significant intervention effects on irritability or subjective mood ( p >
      0.05). The music intervention showed significant reduction in the behavioral and
      psychological symptoms in Chinese elderly patients with dementia. Elderly homes
      could adopt this practical non-pharmacological intervention as a strategy to
      improve the well-being of the elderly.

PMID- 29468886
TI  - Protective Effect of Kolaviron on Cyclophosphamide-Induced Cardiac Toxicity in
      Rats.
AB  - BACKGROUND: Cyclophosphamide (CP) is a nitrogen mustard alkylating drug used for
      the treatment of chronic and acute malignant lymphomas, myeloma, leukemia,
      neuroblastoma, adenocarcinoma, retinoblastoma, breast carcinoma, and
      immunosuppressive therapy. Despite its vast therapeutic uses, it is known to
      cause severe cardiac toxicity. Kolaviron (KV), a Garcinia kola seed extract
      containing a mixture of flavonoids, is reputed for its antioxidant and membrane
      stabilizing properties. OBJECTIVE: This study investigated the protective effect
      of KV on CP-induced cardiotoxicity in rats. METHODS: Thirty rats were used, and
      they were divided into 6 groups of 5 rats each. Group I received 2 mL/kg
      propylene glycol orally for 14 days; group II received CP (50 mg/kg/d,
      intraperitoneally [i.p.]) for 3 days; groups III and IV received 200 and 400
      mg/kg/d KV, respectively, orally for 14 days and groups V and VI were pretreated
      with 200 and 400 mg/kg/d KV, respectively, orally for 14 days followed by CP (50
      mg/kg/d, i.p.) for 3 days. RESULTS: CP treatment resulted in a significantly
      lower food consumption and body weight in rats. The lactate dehydrogenase and
      creatine kinase enzymes in cardiac tissues of rats treated with CP were
      significantly higher. In cardiac tissues, 3-day doses of CP resulted in
      significantly higher heart weight, cardiac troponin I, myeloperoxidase,
      malondialdehyde, hydrogen peroxide and lower superoxide dismutase, catalase,
      glutathione peroxidase activities, and reduced glutathione levels. Histological
      examination of cardiac tissues showed sign of necrosis of myocardium after CP
      treatment. However, administration of KV at 200 and 400 mg/kg for 14 days prior
      to CP treatment, increase food consumption, body weight, and attenuates the
      biochemical and histological changes induced by CP. CONCLUSIONS: These results
      revealed that KV attenuates CP-induced cardiotoxicity by inhibiting oxidative
      stress and preserving the activity of antioxidant enzymes.

PMID- 29468889
TI  - Chemical composition, antimicrobial and antioxidant activities of the essential
      oils of three Uzbek Lamiaceae species.
AB  - The chemical composition of the essential oil from the aerial parts of three
      Lamiaceae species from Uzbekistan was investigated by GC-MS analysis. beta
      Linalool (26.6%), alpha-terpineol (10.0%), coumarin (8.9%) and 4,5,7,7alpha
      tetrahydro-4,4,7alpha-trimethyl-2(6H)-benzofuranone (5.4%) resulted as the main
      components of Ajuga turkestanica essential oil, while camphene (17.1%), 1,8
      cineole (15.9%), beta-cymene (7.9%) and limonene (7.4%) in Phlomis regelii. The
      essential oil of Thymus seravschanicus was dominated by thymol (37.5%),
      phellandral (26.0%), tau-terpinene (6.6%) and beta-cymene (5.2%). The essential
      oils had considerable antimicrobial activity against different bacterial strains
      and fungi. Among the tested samples of essential oils, P. regelii essential oil
      has the significant antioxidant activity with IC50 value of 117.8 +/- 8.02
      MUg/mL.

PMID- 29468888
TI  - Synthesis, characterization and in vitro evaluation of magnetic nanoparticles
      modified with PCL-PEG-PCL for controlled delivery of 5FU.
AB  - Magnetic nanoparticles have properties that cause to apply them in cancer therapy
      and vehicles for the delivery of drugs such as 5FU, especially when they are
      modified with biocompatible copolymers. The aim of this study is to modify
      superparamagnetic iron oxide nanoparticles (SPIONPs) with PCL-PEG-PCL copolymers
      and then utilization of these nanoparticles for encapsulation of anticancer drug
      5FU. The ring-opening polymerization (ROP) was used for the synthesis of PCL-PEG
      PCL copolymer by epsilon-caprolactone (PCL) and polyethylene glycol (PEG2000). We
      used the double emulsion method (water/oil/water) to prepare 5FU-encapsulated
      Fe3O4 magnetic nanoparticles modified with PCL-PEG-PCL copolymer. Chemical
      structure and magnetic properties of 5FU-loaded magnetic-polymer nanoparticles
      were investigated systematically by employing FT-IR, XRD, VSM and SEM techniques.
      In vitro release profile of 5FU-loaded NPs was also determined. The results
      showed that the encapsulation efficiency value for nanoparticles were 90%.
      Moreover, the release of 5FU is significantly higher at pH 5.8 compared to pH
      7.4. Therefore, these nanoparticles have sustained release and can apply for
      cancer therapy.

PMID- 29468890
TI  - A systematic review of the traits and cognitions associated with use of and
      belief in complementary and alternative medicine (CAM).
AB  - Complementary and alternative medicine (CAM) use is widespread despite the
      controversy over its effectiveness. Although previous reviews have examined the
      demographics and attitudes of CAM users, there is no existing review on the
      traits or cognitions which characterise either CAM users or those who believe in
      CAM effectiveness. The current systematic review set out to address these gaps in
      the literature by applying a narrative synthesis. A bibliographic search and
      manual searches were undertaken and key authors were contacted. Twenty-three
      papers were selected. The trait openness to experience was positively associated
      with CAM use but not CAM belief. Absorption and various types of coping were also
      positively associated with CAM use and belief. No other trait was reliably
      associated with CAM use or belief. Intuitive thinking and ontological confusions
      were positively associated with belief in CAM effectiveness; intuitive thinking
      was also positively associated with CAM use. Studies researching cognitions in
      CAM use/belief were mostly on non-clinical samples, whilst studies on traits and
      CAM use/belief were mostly on patients. The quality of studies varied but
      unrepresentative samples, untested outcome measures and simplistic statistical
      analyses were the most common flaws. Traits and cognition might be important
      correlates of CAM use and also of faith in CAM.

PMID- 29468891
TI  - Two new prenylated isoflavones from Maclura cochinchinensis collected in Hoa Binh
      province Vietnam.
AB  - Two new prenylisoflavones, 3',4',5-trihydroxy-8-prenyl
      dihydrofuran[2",3":7,6]isoflavone (1) and 4',5-dihydroxy-8-prenyl
      dihydrofuran[2",3":7,6]isoflavone (2), along with five known prenylisoflavones (3
      7), benzylalcohol-4-O-beta-d-glucoside (8) and two cinnamic acid esters (9, 10)
      were isolated from the leaves of Maclura cochinchinensis (Cudrania
      cochinchinensis). Their structures were elucidated by analysis of NMR (1H-, 13C
      NMR, HSQC, HMBC), MS spectra and comparison with the published data. Compounds 4
      10 were the first time isolated from this species. Prenylisoflavones 1-4 and 6-7
      were evaluated for their in vitro cytotoxic activity on KB and HepG2 cancer cell
      lines. Compound 4 showed cytotoxic activity against both cancer cell lines with
      IC50 values of 26.99 and 19.95 MUM, respectively. The other compounds were
      considered as inactive.

PMID- 29468893
TI  - Correction to: Piran M, et al., In vitro fibroblast migration by sustained
      release of PDGF-BB loaded in chitosan nanoparticles incorporated in electrospun
      nanofibers for wound dressing applications.

PMID- 29468892
TI  - The use of music in aged care facilities: A mixed-methods study.
AB  - Music is frequently used in aged care, being easily accessible and cost
      effective. Research indicates that certain types of musical engagement hold
      greater benefits than others. However, it is not clear how effectively music is
      utilized in aged care facilities and what the barriers are to its further use.
      This study used a mixed-methods paradigm, surveying 46 aged care workers and
      conducting in-depth interviews with 5, to explore how music is used in aged care
      facilities in Australia, staff perceptions of the impact of music on residents,
      and the barriers to more effective implementation of music in aged care settings.

PMID- 29468894
TI  - Biologically active oligostilbenes from the stems of Vatica mangachapoi and
      chemotaxonomic significance.
AB  - Phytochemical investigation of the stems of Vatica mangachapoi (Dipterocarpaceae)
      led to the isolation and structural elucidation of twenty-seven oligostilbenes (1
      27), including a new natural compound 1. The structure of 1 was elucidated on the
      basis of spectroscopic analyses including NMR, MS and ECD data, and the known
      compounds were identified by comparisons with those reported in the literature.
      The absolute configuration of 1 was first time determined by a combination of
      NOESY spectrum and quantum chemical computation. Among of isolates were tested
      for their anti-osteoporosis and anti-HIV-1 activities in vitro by the MTT method.
      Moreover, the chemotaxonomic significance of these compounds was summarised.

PMID- 29468895
TI  - Biotransformation of two furanocoumarins by the fungi species Aspergillus sp.
      PTCC 5266 and Aspergillus niger PTCC 5010.
AB  - The microbial transformations of peucedanin and oreoselon by the fungi
      Aspergillus niger and Aspergillus sp. were investigated for the first time.
      Incubation of peucedanin with A. niger yielded a new hydroxylated metabolite with
      high yield (56%), which was characterized as 2-(1-hydroxypropan-2-yl)-3-methoxy
      7H-furo[3,2-g]chromen-7-one. Oreoselon was converted to a new reduced metabolite
      methyl 3-(2,3-dihydro-6-hydroxy-2-isopropyl-3-oxobenzofuran-5-yl)propanoate in
      biotransformation by Aspergillus sp. The structures of the metabolites were
      determined by spectroscopic methods including IR, EI-MS, 1H NMR, 13C NMR, and
      elemental analysis.

PMID- 29468896
TI  - Real-world evaluation of Hba1c, blood pressure, and weight loss among patients
      with type 2 diabetes mellitus treated with canagliflozin: an analysis of
      electronic medical records from a network of hospitals in Florida.
AB  - OBJECTIVE: Clinical trials and real-world studies reported that canagliflozin
      (CANA) improved HbA1c, blood pressure (BP), and weight in patients with type 2
      diabetes mellitus (T2DM). This study examines if previous results hold regionally
      and within specific patient sub-groups. METHODS: Adults with T2DM and >=12 months
      of clinical activity before the first CANA prescription (index) were identified
      in electronic medical records (January 1, 2012-February 15, 2017) from a network
      of hospitals in Florida. Quality measures were described at baseline and 3, 6, 9,
      and 12 months post-index. Selected thresholds were HbA1c < 7%, BP < 140/90 mmHg,
      and weight loss >=5%. Sub-groups included patients >=65 years old, with African
      American race, with CANA dose increase, initiating CANA in an endocrinology
      setting, and initiating CANA in a primary care setting. RESULTS: Overall, 1,259
      patients (mean age = 56.7 years; 51.2% female, 70.4% White) were identified.
      Among patients with a baseline HbA1c >= 7%, 16.1% had an HbA1c < 7% 3 months
      following CANA initiation, and the mean HbA1c decreased from 8.8% to 8.1%. Among
      patients with a baseline systolic BP >=140 mmHg or diastolic BP >= 90 mmHg, 59.3%
      attained a systolic BP < 140 mmHg and 77.3% a diastolic BP < 90 mmHg after 3
      months. HbA1c and BP responses were sustained through 12 months. The proportion
      of patients with a weight loss from baseline >=5% increased from 17.0% at 3
      months to 31.1% at 12 months. Consistent trends were observed for all sub-groups.
      CONCLUSIONS: In CANA-treated patients and patient sub-groups from a network of
      Florida hospitals, improvements in quality measures and response durability were
      similar to clinical trials and other real-world studies.

PMID- 29468897
TI  - Extracts of the unripe fruit of Ilex paraguariensis as a potential chemical
      control against the golden apple snail Pomacea canaliculata (Gastropoda,
      Ampullariidae).
AB  - Plant extracts can provide a viable alternative to controlling many crop pests.
      This study sought to assess the efficacy of vegetable extracts of the unripe
      fruits of Ilex paraguariensis (yerba mate) for chemical control of the channeled
      apple snail (Pomacea canaliculata) and of non-target species as the South
      American catfish (Rhamdia quelen) under laboratory conditions. In P.
      canaliculata, the LC50 of the decoction extract was 31.39 mg.L-1 and the LT50 was
      over 26 h. The LC50 of the butanol extract was 24.75 mg.L-1 and the LT50 was in
      the range of 28 to 32 h. In juvenile R. quelen, the LC50 of the decoction was
      17.98 mg.L-1 and the LT50 was in the range of 10-12 h. These extracts are
      particularly attractive considering the source of compounds and their
      effectiveness as molluscicides.

PMID- 29468898
TI  - Paratonia in Flemish Nursing Homes: Current State of Practice.
AB  - BACKGROUND: Paratonia is a major underlying motor problem impeding functionality
      and locomotion in dementia. Despite its undeniable impact on patient's quality of
      life and daily care, there is a lack of evidence-based therapy on patients with
      this condition. METHODS: We surveyed physiotherapists working in nursing homes in
      Flanders (Belgium) concerning the use and perceived effect of therapeutic
      strategies and positioning methods/aids. RESULTS: Positioning and soft passive
      mobilization were the most applied and positively appraised therapeutic
      interventions. Highest ratings for positioning were found for C-shaped
      positioning cushions and multi-position wheelchair. According to the respondents,
      key points for paratonia approach were relaxation, positioning, active movement
      stimulation, and-to some extent-passive mobilization. Indispensable for any
      success however is multidisciplinary cooperation. CONCLUSION: These findings
      might provide an inspirational path for research to verify possible (evidence
      based) beneficial treatments that could be applied to improve current and future
      treatment of patients with paratonia.

PMID- 29468899
TI  - Markhacanasin C, cycloartane triterpenoid from the leaves of Markhamia stipulata
      var. canaense V.S. Dang.
AB  - One new cycloartane triterpenoid, named markhacanasin C (1), together with three
      known triterpenoids, oleanolic acid (2), ursolic acid (3) and 6beta,19alpha
      dihydroxyursolic acid (4) were isolated by various chromatographic methods from
      the most cytotoxic fraction of the ethyl acetate extract of Markhamia stipulata
      var. canaense V.S. Dang leaves. Among them, 4 was reported for the first time
      from the genus Markhamia, while 2 and 3 were found for the first time from this
      species. Their structures were elucidated by IR, UV, HR-ESI-MS and NMR
      experiments. The cytotoxicity of isolated compounds (3 and 4) against three human
      cancer cell lines (HeLa, HepG2, and MCF-7) were evaluated. At the concentration
      of 100 MUg/mL, 3 exhibited significant cytotoxic activity (86.36 +/- 3.69%).

PMID- 29468900
TI  - Health promotion in young people: identifying the predisposing factors of self
      care health habits.
AB  - Unhealthy behaviors are strongly associated with chronic diseases, disabilities,
      or mortality. Identifying the predisposing factors that influence on self-care
      healthy habits will improve an early detection of high-risk groups. Four hundred
      and sixty-six Spanish young people aged 18-25 years were assessed. Global
      perceived health self-care was predicted by Value of health and
      Conscientiousness, both in females ( R2 = 0.185; F = 29.661; p < 0.001) and males
      ( R2 = 0.154; F = 17.849; p < 0.001). The results have shown gender differences
      in health self-care habits. Health promotion policies should include specific
      health consciousness-based strategies.

PMID- 29468901
TI  - Osteochondritis Dissecans of the Knee - Conservative Treatment Strategies: A
      Systematic Review.
AB  - Objective Osteochondritis dissecans (OCD) lesions are a relevant problem that
      affects the long-term prognosis of young patients. The purpose of this study was
      to analyze the evidence on potential and indications of nonsurgical treatment
      strategies for knee OCD. Design The search was conducted on 3 medical electronic
      databases according to PRISMA guidelines, including reports of any level of
      evidence dealing with the conservative management of knee OCD. Of 1688 identified
      records, 55 full-text articles were screened: 27 studies met the inclusion
      criteria, for a total of 908 knees, and were used for the analysis. Results No
      high-level studies were found: 24 articles were case series and 3 case reports,
      reporting on different treatments summarized in (1) restriction of physical
      activity, (2) physiokinesitherapy and muscle-strengthening exercises, (3)
      physical instrumental therapies, (4) limitation of weightbearing, and (5)
      immobilization. The analysis showed an overall healing rate of 61.4%, with large
      variability (10.4%-95.8%). A conservative treatment based on restriction of sport
      and strenuous activities seems a favorable approach, possibly combined with
      physiokinesitherapy. Negative prognostic factors were also identified: larger
      lesion size, more severe lesion stages, older age and skeletal maturity, discoid
      meniscus, and clinical presentation with swelling or locking. Conclusions The
      literature on conservative treatments for knee OCD is scarce. Among different non
      surgical treatment options, strenuous activity restriction seems a favorable
      approach, whereas there is no evidence that physical instrumental therapy,
      immobilization, or weightbearing limitation could be beneficial. However, further
      studies are needed to improve treatment potential and indications for the
      conservative management of knee OCD.

PMID- 29468902
TI  - Local Anesthetics' Toxicity toward Human Cultured Chondrocytes: A Comparative
      Study between Lidocaine, Bupivacaine, and Ropivacaine.
AB  - Objective In orthopedic joint injection, the most frequently used local
      anesthetics are ropivacaine, bupivacaine, and 1% or 2% lidocaine. The aim of this
      study was to examine effects of these various anesthetics on the viability of
      human chondrocytes. Our hypothesis was that all local anesthetics tested damage
      human chondrocytes in vitro. Methods Primary human chondrocytes were isolated and
      cultured from 6 donated human knee joints (mean age of donors 61.2 years). Local
      anesthetics were added to these cultures. Toxicity analysis was performed by
      visualization of cell structure using light microscopy. Determination of vital
      chondrocytes was performed by use of a Casy cell counter. Chondrocytes' cell
      death was examined by fluorescence microscopy and an XTT ELISA assay. Results
      Light microscope and fluorescence microscope data revealed a defect cell
      structure and increased number of dead cells after addition of 1% or 2% lidocaine
      and bupivacaine but not ropivacaine. We were able to show an increased level of
      XTT activity after treatment with bupivacaine, 2% lidocaine or ropivacaine. The
      count of vital chondrocytes was significantly decreased after treatment with
      bupivacaine, 1% or 2% lidocaine, and ropivacaine. Conclusions The data show that
      treatment with local anesthetics induces cell damage of human chondrocytes in
      vitro. Ropivacaine seems to be a local anesthetic with the lowest toxic potential
      on human chondrocytes, a feature that may favor its preference for use in joint
      injection.

PMID- 29468903
TI  - A new benzofuran from Artemisia halodendron Turcz. ex Bess.
AB  - A new benzofuran, methyl (2S,2"S,3'E)-[2-(1"-acetoxypropan-2-yl)-2,3
      dihydrobenzofuran-5-yl]acrylate (1), and 13 known compounds (2-14) were isolated
      from an ethanol extract of Artemisia halodendron Turcz. ex Bess. The chemical
      structures of these compounds were determined by 1D and 2D NMR (1H-1H COSY, HMBC,
      HMQC and NOESY) and HR-ESI-MS spectra, and results were compared with data from
      the literature. The effects of compounds 1-14 were measured on NF-kappaB
      activation, with compounds 2 and 3 exhibiting inhibitory activities against TNF
      alpha-induced NF-kappaB reporter gene expression in HeLa cells from 10 to 100
      MUM.

PMID- 29468904
TI  - The experiences of general practitioner partners living with distress: An
      interpretative phenomenological analysis.
AB  - Doctors, including general practitioners, experience higher levels of mental
      illness than the general population. General practitioners who are partners in
      their practices may face heightened stress. In total, 10 general practitioner
      partners living with work-related distress were interviewed, and transcripts were
      analysed using interpretative phenomenological analysis. Three major themes
      arose: (1) extreme distress, (2) conflicted doctor identity and (3) toxic versus
      supportive workplace relationships. Participants detailed symptoms of depression,
      anxiety and burnout; reported conflicted identities; and discussed the impact of
      bullying partnerships. We recommend that organisational interventions tackling
      issues such as bullying be implemented and opportunities to debrief be offered as
      protected time activities to general practitioner partners.

PMID- 29468905
TI  - The effect of viewing fitness imagery on body dissatisfaction: sex and physical
      activity differences.
AB  - Exposure to cultural bodily ideals featuring thinness and muscularity can have
      deleterious effects on body satisfaction. The current study explores the effect
      of exposure to such imagery on body dissatisfaction and the influence of
      internalisation of cultural and athletic ideals. 188 (97 male) adults (18-25yrs;
      M = 20.97) were grouped according to a 2 * 2 * 2 mixed between-within subjects
      design (male/female; high/low physical activity; intervention/control).
      Participants were exposed to images of idealised physiques or neutral images.
      Internalisation-general, sex, physical activity levels, and Body Mass Index were
      associated with baseline levels of body dissatisfaction. Internalisation of
      cultural ideals appears to be an important factor for the prediction of body
      dissatisfaction. Exposure to idealised images resulted in increases in body
      dissatisfaction across all groups compared to controls. Neither sex nor physical
      activity levels buffer young adults from the negative effects of viewing images
      featuring idealised bodies.

PMID- 29468907
TI  - Heads up: Could sport psychology be used to aide medical training?

PMID- 29468906
TI  - Quantification of 10 steroid hormones in human saliva from Chinese adult
      volunteers.
AB  - Objective This study was performed to investigate the effects of age and sex on
      10 salivary steroid hormones and analyze the correlations between salivary and
      plasma hormones. Methods The concentrations of 10 salivary steroid hormones in
      1090 Chinese adult volunteers were examined using liquid chromatography-tandem
      mass spectrometry, and a related investigation was performed on the
      concentrations of salivary hormones in this population. Results The
      concentrations of androstenedione (A4), 17alpha-hydroxyprogesterone (17-OHP),
      aldosterone (ALD), cortisone (COR), corticosterone (CORT), cortisol (F),
      progesterone (P), and testosterone were significantly different between men and
      women (Student's t-test). Differences in 17-OHP and ALD concentrations were
      highly significant between women in the follicular and luteal phases of their
      menstrual cycle (Student's t-test). Five salivary steroid hormones (17-OHP, A4,
      CORT, COR, and F) significantly decreased with increasing age (Kruskal-Wallis
      test). A high linear correlation between salivary and plasma 17-OHP, P, A4, and F
      were observed with obvious sex-related differences (Pearson's correlation, r >
      0.7). Conclusions Our results provide important knowledge regarding the
      descriptive characteristics of salivary hormones in relation to age and sex and
      their correlations with plasma hormones.

PMID- 29468909
TI  - Erratum: Gough et al (2017).
AB  - In the article by Gough, L.A., Rimmer, S., Osler, C.J., & Higgins, M.F. (2017).
      Ingestion of sodium bicarbonate (NaHCO3) following a fatiguing bout of exercise
      accelerates postexercise acid-base balance recovery and improves subsequent high
      intensity cycling time to exhaustion, International Journal of Sport Nutrition
      and Exercise Metabolism, 27(5), 429-438, doi: 10.1123/ijsnem.2017-0065 , we did
      not accurately reflect several content and layout corrections which were needed.
      These include: (a) The key for Figure 1 was erroneously included for Figure 3
      (and not for Figure 1). (b) The abbreviation for PRE was missing from the Figure
      1 key. (c) Figure 3 contained two indicators (+) which were not necessary. The
      online version of this article has been corrected. We sincerely apologize for
      these errors.

PMID- 29468908
TI  - Inflammatory bowel disease and anemia: intravenous iron treatment.
AB  - OBJECTIVES: The main objective of our study was to determinate the effectiveness
      of intravenous iron treatment with ferric carboxymaltose in inflammatory bowel
      disease (IBD) patients. Our other objectives were to study parameters that would
      predict a good response to the treatment and to chart out possible side-effects
      of the treatment. MATERIALS AND METHODS: In our retrospective chart review study
      we collected clinical data and laboratory results related to IBD from medical
      records of 87 IBD patients who were treated with ferric carboxymaltose in
      Helsinki University Hospital between 2014 and 2016. RESULTS: The mean increase in
      hemoglobin levels of the patients was 24.6 g/l (+ 24%) after one month, 27.6 g/l
      (+ 27%) after three months and 26.0 g/l (+ 27%) after six months. Nine out of 87
      treated patients (10.3%) reported side-effects during the iron infusion. A linear
      regression model assessing the change in hemoglobin levels after six months
      demonstrated close correlation with transferrin receptor count (p = .004) and
      ferritin (p = .016) with an adjusted R square of 0.463. CONCLUSION: Ferric
      carboxymaltose was found to be an effective and well tolerated treatment for iron
      deficiency anemia in patients with IBD. The results of our study further
      strengthen the current knowledge of the effectiveness and safety of the
      treatment.

PMID- 29468910
TI  - Definitive re-irradiation using intensity-modulated radiation therapy in cancers
      of the head and neck, focusing on rare tumors.
AB  - PURPOSE: To analyze the outcomes following re-irradiation for local recurrence of
      rare head and neck tumors. MATERIAL AND METHODS: We retrospectively analyzed 11
      patients who had received intensity-modulated radiation therapy (IMRT) for
      recurrent tumors in the head and neck except for laryngopharynx. RESULTS: Primary
      tumor sites included the maxillary sinus, nasal cavity, and external ear canal in
      six, three, and two patients, respectively. The median follow-up times were 13
      (range, 3-54) months. The median survival time was 17 months with 1- and 2-year
      survival rates of 63.64 and 39.77%, respectively. Among 11 patients, five
      experienced local failure in the follow-up period. The 1- and 2-year local
      control rates were 58 and 47%, respectively. Patients who had received a
      radiation dose of >=3 Gy per fraction showed significantly better local control
      than those receiving less (p = .0419). One patient experienced Grade 3 facial
      pain as acute toxicity. Late toxicities included radiographic findings of partial
      central nervous system necrosis in three patients and Grade 3 osteonecrosis and
      Grade 3 facial nerve disorder in one patient. CONCLUSIONS: Re-irradiation of rare
      head and neck tumors using IMRT for loco-regional recurrence may be an acceptable
      treatment option.

PMID- 29468911
TI  - Reality of obesity paradox: Results of percutaneous coronary intervention in
      Middle Eastern patients.
AB  - Objective The aim of this study was to assess the baseline clinical
      characteristics, coronary angiographic features, and adverse cardiovascular
      events during hospitalization and at 1 year of follow-up in obese patients
      compared with overweight and normal/underweight patients. Methods A prospective,
      multicenter study of consecutive patients undergoing percutaneous coronary
      intervention was performed. Results Of 2425 enrolled patients, 699 (28.8%) were
      obese, 1178 (48.6%) were overweight, and 548 (22.6%) were normal/underweight.
      Obese patients were more likely to be female and to have a higher prevalence of
      diabetes, hypertension, hypercholesterolemia, or previous percutaneous coronary
      intervention. Acute coronary syndrome was the indication for percutaneous
      coronary intervention in 77.0% of obese, 76.4% of overweight, and 77.4% of
      normal/underweight patients. No significant differences in the prevalence of
      multi-vessel coronary artery disease or multi-vessel percutaneous coronary
      intervention were found among the three groups. Additionally, no significant
      differences were found in stent thrombosis, readmission bleeding rates, or
      cardiac mortality among the three groups during hospitalization, at 1 month, and
      at 1 year. Conclusion The major adverse cardiovascular event rate was the same
      among the three groups throughout the study period. Accordingly, body mass index
      is considered a weak risk factor for cardiovascular comorbidities in Arab
      Jordanian patients.

PMID- 29468913
TI  - The EPA-based Utrecht undergraduate clinical curriculum: Development and
      implementation.
AB  - AIM: As reports of the application of entrustable professional activities (EPAs)
      increase, not only for postgraduate but also for undergraduate medical education,
      there is a need for descriptions of what a UME curriculum with EPAs could look
      like. We provide such a description based on the experiences at University
      Medical Center Utrecht, the Netherlands, which can be used as an example by other
      curriculum developers. METHODS: In a three-year process, the UMC Utrecht
      Curriculum Committee developed a clinical workplace curriculum with an EPA
      structure, taking into account examples, such as the US Core EPAs for Entering
      Residency, and recommendations to integrate and increase the length of
      clerkships. RESULTS: In the resulting curriculum, operational from 2016, students
      train to be trusted with indirect supervision before graduation in five broad
      EPAs: the clinical consultation; general medical procedures; informing, advising
      and guiding patients and families; communicating and collaborating with
      colleagues; and extraordinary patient care. Each of these integrates smaller
      (nested) EPAs that receive focused training attention in integrated clerkships at
      various moments and must be signed off for entrustment with indirect supervision
      to complete the clerkship. DISCUSSION: The framework of EPAs went through many
      iterations before it was consolidated. Among the issues that required special
      attention was the application of a supervision levels scale for sign-off, the
      necessity to cover all relevant clinical content while not labeling too many
      small tasks each as a separate EPA, methods of EPA-focused assessment in the
      workplace and the creation of an e-portfolio model to serve assessment and
      entrustment.

PMID- 29468914
TI  - Methotrexate-induced lymphoproliferative disorders: regression matters.

PMID- 29468912
TI  - Hormone treatments in congestive heart failure.
AB  - The common ultimate pathological feature for all cardiovascular diseases,
      congestive heart failure (CHF), is now considered as one of the main public
      health burdens that is associated with grave implications. Neurohormonal systems
      play a critical role in cardiovascular homeostasis, pathophysiology, and
      cardiovascular diseases. Hormone treatments such as the newly invented dual
      acting drug valsartan/sacubitril are promising candidates for CHF, in addition to
      the conventional medications encompassing beta receptor blockers, angiotensin
      converting enzyme inhibitors, angiotensin receptor blockers, and
      mineralocorticoid receptor antagonists. Clinical trials also indicate that in CHF
      patients with low insulin-like growth factor-1 or low thyroid hormone levels,
      supplemental treatment with growth hormone or thyroid hormone seems to be
      cardioprotective; and in CHF patients with volume overload the vasopressin
      antagonists can relieve the symptoms superior to loop diuretics. Furthermore, a
      combination of selective glucocorticoid receptor agonist and mineralocorticoid
      receptor antagonist may be used in patients with diuretic resistance. Finally,
      the potential cardiovascular efficacy and safety of incretin-based therapies,
      testosterone or estrogen supplementation needs to be prudently evaluated in large
      scale clinical studies. In this review, we briefly discuss the therapeutic
      effects of several key hormones in CHF.

PMID- 29468915
TI  - Association between sarcopenia and erectile dysfunction in males with type II
      diabetes mellitus.
AB  - BACKGROUND: The prevalence rates for both sarcopenia and erectile dysfunction
      (ED) gradually increase in middle-aged and elderly diabetic male population and
      they impair physical functioning, sexual functioning, and quality of life. The
      aim of the present study was to evaluate the sarcopenia in patients with diabetic
      ED. METHODS: The study included 98 male patients with type II diabetes mellitus
      (DM) aged 18-80 years. Blood chemistry and hormone levels were obtained. The
      International Index of Erectile Function (IIEF-5) questionnaire was administered
      to the patients. The patients were divided into three groups according to the
      IIEF-5 score; a score of 5-10 points indicated severe ED, a score of 11-20
      indicated moderate ED, and a score of 21-25 points indicated no ED. The muscle
      mass, handgrip strength, timed up and go test, upper mid-arm circumference, calf
      circumference, and body mass index were obtained. The statistical analysis was
      performed using MedCalc Statistical Software version 12.7.7. All parameters were
      compared between the three groups. RESULTS: Of 98 patients included in the study,
      84 patients had severe sarcopenia, 13 had moderate sarcopenia, while only one
      patient had normal muscle mass. The mean age was 56.59 +/- 11.46 years. When
      patients were divided into three groups according to IIEF-5 score, 38 had severe
      ED, 39 had moderate ED, and 21 had no ED. There was a significant difference
      between the three groups in terms of handgrip strength, timed up and go test
      scores, upper mid-arm circumference, and calf circumference (p < .05 for all).
      CONCLUSIONS: Although muscle mass remains unchanged, muscle strength and physical
      performance decrease in diabetic ED patients. Diabetic patients with severe and
      moderate ED have lower muscle strength and physical performance.

PMID- 29468916
TI  - The safety of gliptins : updated data in 2018.
AB  - INTRODUCTION: Dipeptidyl peptidase-4 inhibitors (DPP-4is) are generally
      considered as glucose-lowering agents with a safe profile in type 2 diabetes.
      Areas covered: An updated review of recent safety data from randomised controlled
      trials, observational studies, meta-analyses, pharmacovigilance reports regarding
      alogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin, with a
      special focus on risks of hypoglycemia, pancreatitis and pancreatic cancer, major
      cardiovascular events, hospitalisation for heart failure and other new safety
      issues, such as bone fractures and arthralgia. The safety of DPP-4i use in
      special populations, elderly patients, patients with renal impairment, liver
      disease or heart failure, will also be discussed. Expert opinion: The good
      tolerance/safety profile of DPP-4is has been largely confirmed, including in more
      fragile populations, with no gastrointestinal adverse effects and a minimal risk
      of hypoglycemia. DPP-4is appear to be associated with a small increased incidence
      of acute pancreatitis in placebo-controlled trials, although most observational
      studies are reassuring. Most recent studies with DPP-4is do not confirm the
      increased risk of hospitalisation for heart failure reported with saxagliptin in
      SAVOR-TIMI 53, but further post-marketing surveillance is still recommended. New
      adverse events have been reported such as arthralgia, yet a causal relationship
      remains unclear.

PMID- 29468917
TI  - The Acute Effects of Aerobic Exercise on Cognitive Flexibility and Task-Related
      Heart Rate Variability in Children With ADHD and Healthy Controls.
AB  - OBJECTIVE: To investigate cognitive flexibility and task-related heart rate
      variability following moderately intense aerobic exercise and after watching a
      video in both children with ADHD and healthy controls. METHOD: Using a cross-over
      design, participants completed cognitive assessments following exercise and a
      physically inactive control condition. Behavioral performance was assessed using
      the Alternate Uses task. Heart rate variability was recorded via
      electrocardiography during the cognitive task. RESULTS: The statistical analysis
      revealed that in comparison with the control condition, both groups showed higher
      cognitive flexibility following aerobic exercise. Moreover, decreased low
      frequency and high frequency power was observed in the exercise condition.
      CONCLUSION: The findings suggest that exercise elicits similar benefits for
      cognitive flexibility in children with ADHD and healthy controls, partly due to
      an increase in arousal induced by parasympathetic withdrawal.

PMID- 29468918
TI  - Relations Between Sleep and Temperament in Preschool Children With ADHD.
AB  - OBJECTIVE: The objective of this study was to assess the links between
      temperament and sleep in a group of preschoolers with ADHD. METHOD: Twenty-five
      ADHD ( M = 5.37 years, SD = 1.09) and 22 typically developing (TD; M = 5.10, SD =
      1.18) preschoolers participated in the study. Sleep was assessed with the Sleep
      Disturbance Scale and wrist actigraphy. The Preschool Temperament and Character
      Inventory (PsTCI) was used to evaluate the child temperament. RESULTS: ADHD
      children showed a temperamental profile characterized by higher novelty seeking,
      lower persistence, self-directness, and cooperativeness and marginally lower harm
      avoidance (HA) compared with controls. HA was associated negatively to
      wakefulness after sleep onset and sleep fragmentation and positively with sleep
      efficiency and sleep time. Reward dependence was negatively associated with wake
      episode length. CONCLUSION: Sleep and temperament are correlated in preschoolers
      with ADHD and temperament might represent an intermediate endophenotype
      underlying the relation between ADHD and sleep disorders.

PMID- 29468919
TI  - Health-related quality of life in hearing-impaired adolescents and children.
AB  - OBJECTIVE: To evaluate health-related quality of life (HRQoL) in hearing-impaired
      adolescents and children and to compare it with that of hearing individuals.
      STUDY DESIGN AND SETTING: Hearing-impaired adolescents and children were
      recruited to the study during their annual control visit to the Hearing Clinic of
      Helsinki University Hospital. They filled in a HRQoL questionnaire, either the 16
      dimensional 16D (adolescents aged 12-17 years) or the 17-dimensional 17D
      (children aged 7-11 years). The total HRQoL scores were compared with previously
      collected data, matched for age and gender, from adolescents and children without
      any known handicaps or illnesses. RESULTS: In total 50 adolescents and 50
      children completed the questionnaire. Of the 16/17 dimensions of the HRQoL
      instrument, hearing and communication were affected the most. The total HRQoL
      scores were somewhat lower in adolescents and children with hearing impairment
      than in the general populations of age-matched peers (p < .001 for adolescents
      and .030 for children). CONCLUSIONS: HRQoL in hearing-impaired adolescents and
      children is only slightly worse than in hearing adolescents and children.
      SIGNIFICANCE: This study evaluates the impact of hearing loss on HRQoL to enhance
      the care of these children.

PMID- 29468920
TI  - Training medical students for the twenty-first century: Rationale and development
      of the Utrecht curriculum "CRU+".
AB  - AIM: The aim of this report, written for the 40th anniversary issue of Medical
      Teacher, is to document 20 years of development of the Utrecht undergraduate
      medical curriculum, as both to exhibit accountability and to inform the community
      of the process and choices that can be made in long-term curriculum development.
      METHODS: We used the SPICES model, created by Medical Teacher's Editor Ronald
      Harden and colleagues in 1984. RESULTS: The Utrecht six-year program, now called
      "CRU+", has many distinct features that were introduced, most of which are well
      documented. A limited selection includes  * A new 3+3 years Bachelor-Master
      structure following the EU Bologna rules leading to MD registration for cohorts
      of about 300.  * Horizontally integrated classroom teaching of basic sciences
      with clinical disciplines predominantly in groups of 12 and limited lectures.  *
      Mandatory knowledge retention tests, retesting the clinically relevant core
      knowledge from block tests of semesters one through four.  * Vertical integration
      not only linking clinical experience with background knowledge, but also
      exemplified by a stepwise increase in health care responsibilities throughout the
      curriculum.  * A final year focussing on growth towards the level of a primary
      responsible physician in a 12-week sub-internship for a limited number of
      patients and beds, in a chosen specialty. The student is called a semi-physician
      in the clerkship of this transitional year to residency.  * Teaching skills
      training for all medical graduates, an elective teaching rotation and various
      peer-teaching arrangements throughout the curriculum.  * Integrated semi
      longitudinal clerkships with an assessment focus on entrustment decisions for
      Entrustable Professional Activities. CONCLUSION: UMC Utrecht has made a
      continuous attempt to both develop its medical curriculum and to study and report
      on its development in the literature, regarding new methods found and insights
      derived. UMC Utrecht will remain committed to developing training to meet twenty
      first century demands of medical graduates.

PMID- 29468921
TI  - Cross-species comparison of the metabolism and excretion of selexipag.
AB  - 1. The metabolism of the prostacyclin receptor agonist selexipag (NS-304; ACT
      293987) and its active metabolite MRE-269 (ACT-333679) has been investigated in
      liver microsomes and hepatocytes of rats, dogs, and monkeys. MRE-269 formation is
      the main pathway of selexipag metabolism, irrespective of species. Some
      interspecies differences were evident for both compounds in terms of both
      metabolic turnover and metabolic profiles. The metabolism of MRE-269 was slower
      than that of selexipag in all three species. 2. The metabolism of selexipag was
      also studied in bile-duct-cannulated rats and dogs after a single oral and
      intravenous dose of [14C]selexipag. MRE-269 acyl glucuronide was found in both
      rat and dog bile. Internal acyl migration reactions of MRE-269 glucuronide were
      identified in an experiment with the synthetic standard MRE-6001. 3. MRE-269 was
      the major component in the faeces of rats and dogs. In ex vivo study using rat
      and dog faeces, selexipag hydrolysis to MRE-269 by the intestinal microflora is
      considered to be a contributory factor in rats and dogs. 4. A taurine conjugate
      of MRE-269 was identified in rat bile sample. Overall, selexipag was eliminated
      via multiple routes in animals, including hydrolysis, oxidative metabolism,
      conjugation, intestinal deconjugation, and gut flora metabolism.

PMID- 29468922
TI  - The impact of perceived discrimination on personality among Chinese migrant
      children: The moderating role of parental support.
AB  - BACKGROUND: Previous research has indicated that perceived discrimination has
      harmful effects on migrant children's physical, mental and behavioral health.
      However, little is known as to whether these harmful effects cumulate to impact
      on migrant children's personalities. AIMS: This study examines the effect of
      perceived discrimination on personality, as well as the moderating role of
      parental support in the discrimination-personality linkage. METHODS: A purposeful
      convenience sample of 215 migrant children in Beijing, China, completed a
      standardized questionnaire. RESULTS: Migrant children experienced a moderate
      level of perceived discrimination, with Form 8 students experiencing greater
      discrimination than lower grades and those with lower family incomes also
      experiencing greater discrimination than those with higher family incomes.
      Perceived discrimination significantly predicted neuroticism; parental support
      significantly predicted extraversion, openness, agreeableness and
      conscientiousness, but the moderating effect of parental support was only
      marginally significant for the relation between discrimination and
      conscientiousness. CONCLUSION: This study underlines the need for researchers and
      policy makers to pay more attention to the impact of perceived discrimination on
      migrant children's personality development.

PMID- 29468923
TI  - Reflux symptom index and reflux finding score in 91 asymptomatic volunteers.
AB  - BACKGROUND: The primary goal of this study was to investigating the symptoms, in
      addition to the reflux-related laryngopharynx inflammation performance of
      asymptomatic, volunteers, and verified the 'normal point'. METHODS: A total of 91
      asymptomatic subjects were recruited for this cross-sectional study between March
      2016 and September 2016. Participants completed the reflux symptom index (RSI)
      assessment and underwent laryngostroboscopic examination using a rigid endoscope.
      Their RFS were graded according to the laryngeal findings. The distribution and
      the relationship of the RSI and the RFS were analyzed. RESULTS: The mean RSI of
      individuals was 2.24 +/- 2.34 [95% confidence interval (CI) = 1.75, 2.72], and
      the mean RFS of individuals was 5.78 +/- 1.74 (95% CI = 5.42, 6.15). The Pearson
      product-moment correlation coefficient of the RSI and RFS scores was -0.084 (n =
      91, p = .428). CONCLUSIONS: Asymptomatic people could present relatively high RFS
      scores, and no linear relationship existed between RSI and RFS.

PMID- 29468924
TI  - Emerging molecular target antagonists for the treatment of biliary tract cancer.
AB  - INTRODUCTION: Biliary tract cancers (BTCs) are a heterogeneous group of cancers,
      characterized by low incidence but poor prognosis. Even after complete surgical
      resection for early stage, relapse is frequent and the lack of effective
      treatments contributes to the dismal prognosis. To date, the only standard
      treatment in first-line is cisplatin/gemcitabine combination, whereas no standard
      in 2nd-line has been defined. Hence, the current goal is to better understand the
      biology of BTCs, discovering new treatment methods and improving clinical
      outcomes. Areas covered: The development of next-generation-sequencing has
      unveiled the picture of the molecular signatures characterizing BTCs, leading to
      the identification of actionable mutations in biomarker-driven clinical trials.
      In this review we will cover the genetic landscape of BTC, focusing on the
      efficacy of existing treatments. Furthermore, we will discuss emerging molecular
      targets and evaluate the findings of pre-clinical studies. Finally, the
      encouraging results of clinical trials involving targeted therapies or
      immunotherapy will be reviewed. Expert opinion: FGFR fusion rearrangements and
      IDH1 or IDH2 mutations are the most promising targeted treatments under
      evaluation. In addition, innovative trial design will allow to offer a chance for
      tailored medicine to infrequent subgroups of BTCs patients based on their
      molecular features rather than their histology.

PMID- 29468925
TI  - Self-Reported ADHD and Adult Health in the United States.
AB  - OBJECTIVE: Informed by a social determinants of health framework, we investigate
      the relationship between self-reported ADHD diagnosis status and adult health,
      and whether observed associations are attenuated by biomedical and socioeconomic
      factors. METHOD: Using 2007 National Health Interview Survey data ( N = 19,104),
      we present multivariate logistic regression analyses of associations between self
      reported ADHD diagnosis status and five adult health outcomes. RESULTS: ADHD
      diagnosis was significantly associated with higher odds of injury, physical
      health conditions, functional limitations, fair/poor health, and psychological
      distress in fully specified models (adjusted odds ratios [AORs] = 1.62-2.36).
      Inclusion of controls for exogenous demographic characteristics, psychiatric
      comorbidities and health behaviors, and adult social and economic statuses
      attenuated but did not eliminate observed associations between ADHD and poorer
      adult health. CONCLUSION: Research on adult health outcomes for those with ADHD
      should include consideration of the mechanisms by which a diagnosis of ADHD leads
      to cumulative social disadvantages that independently contribute to poorer health
      outcomes.

PMID- 29468926
TI  - Development and characterization of HBsAg-loaded Eudragit nanoparticles for
      effective colonic immunization.
AB  - The present study was undertaken with an aim to investigate the potential of
      targeting colonic mucosa following oral vaccine delivery to generate prophylactic
      humoral and mucosal immune response. In present study, response surface
      methodology (RSM) using the central composite design (CCD) was applied for
      optimization of process and composition to get uniform, stable reproducible
      eudragit nanoparticles suitable for targeting to colon. The optimized formulation
      had the composition of 173 MUg HBsAg, 250 mg polymers concentration (4:1
      combination of Eudragit S-100 and L-100) and 2% w/v Polyvinyl alcohol (PVA) along
      with adjuvant Monophosphoryl lipid A (MPLA). Mean particle size of optimized
      nanoparticles was found to be 730.4 nm, entrapment efficiency (58.38%) and
      polydispersity index of 0.185. Fluorescent spectroscopy, differential scanning
      calorimetry, and antigen integrity by SDS-PAGE established that antigen structure
      was preserved during and after formulation development. In-vitro release studies
      in different intestinal pH concluded antigen release at mild alkaline conditions.
      Real time fluorescence animal imaging confirmed the effective absorption and
      distribution of NPs at colon resulted in improved immune response. Present study
      concludes that Eudragit nanoparticles offers strong potential in colon targeting
      of vaccines through oral immunization.

PMID- 29468927
TI  - Inducible Co-Stimulator (ICOS) as a potential therapeutic target for anti-cancer
      therapy.
AB  - INTRODUCTION: The recent success of checkpoint-inhibitors in cancer treatment
      paved the way for the development of new strategies of agonist and antagonist
      agents against B7 superfamily members. Inducible Co-Stimulator (ICOS), a co
      stimulatory receptor for T-cell enhancement, arouses interest. Areas covered: We
      performed an extensive literature search with PUBMED using the keywords 'ICOS'
      and 'cancer' to discuss its involvement in oncogenesis, its expression in
      different malignancies, and its targeting in relevant preclinical studies. We
      also searched the Clinicaltrials.gov database for recent updates on early phase
      clinical trials. Expert opinion: ICOS/ICOSL axis has a dual effect and might
      participate in anti-tumour T cell response as well as a pro-tumour response due
      to its connection with regulatory T-cells (Tregs) suppressive activity.
      Therefore, both antagonist and agonist antibodies might be of interest in the
      targeting ICOS/ICOSL pathway for cancer treatment. In preclinical studies, ICOS
      agonist monoclonal antibodies (mAbs) have shown to potentiate the effect of
      inhibitory checkpoint blockade. In contrast, antagonistic anti-ICOS mAbs could
      not only inhibit lymphoid tumour cells expressing ICOS, but also dampen
      immunosuppressive Tregs. Two agonist and one antagonist mAbs are evaluated in
      phase I/II trials. Efficacy, safety, and combination strategies with anti-ICOS
      agonist or antagonist have yet to be specified.

PMID- 29468928
TI  - The 'work of childhood': understanding school functioning in youth with chronic
      pain.
AB  - School is often cited as the 'work of childhood' and serves as an important site
      for child and adolescent development. Frequent school absences in children and
      adolescents with chronic pain are well documented; however, variables that may
      explain school impairment are not understood. The potential consequences of
      school impairment are extensive, as these children and adolescents are at great
      risk for achieving poor grades and sometimes require full-time homebound
      instruction. This, in turn, can have adverse effects on occupational and social
      functioning well into adulthood. The present review provides a summary of
      selected studies that have investigated why children and adolescents with chronic
      pain may experience disruptions in school functioning. A conceptual model of
      school functioning is presented to summarize factors accumulated to date and to
      guide future investigations.

PMID- 29468930
TI  - Navigating Nuances of Language and Meaning: Challenges of Cross-Language
      Ethnography Involving Shona Speakers Living With Schizophrenia.
AB  - For people living with schizophrenia, their experience is personal and culturally
      bound. Focused ethnography enables researchers to understand people's experiences
      in-context, a prerequisite to providing person-centered care. Data are gathered
      through observational fieldwork and in-depth interviews with cultural informants.
      Regardless of the culture, ethnographic research involves resolving issues of
      language, communication, and meaning. This article discusses the challenges faced
      by a bilingual, primary mental health nurse researcher when investigating the
      experiences of people living with schizophrenia in Zimbabwe. Bilingual
      understanding influenced the research questions, translation of a validated
      survey instrument and interview transcripts, analysis of the nuances of dialect
      and local idioms, and confirmation of cultural understanding. When the researcher
      is a bilingual cultural insider, the insights gained can be more nuanced and
      culturally enriched. In cross-language research, translation issues are
      especially challenging when it involves people with a mental illness and requires
      researcher experience, ethical sensitivity, and cultural awareness.

PMID- 29468929
TI  - Tumor-derived lactate induces M2 macrophage polarization via the activation of
      the ERK/STAT3 signaling pathway in breast cancer.
AB  - Tumor-associated macrophages (TAM) are prominent components of tumor
      microenvironment (TME) and capable of promoting cancer progression. However, the
      mechanisms for the formation of M2-like TAMs remain enigmatic. Here, we show that
      lactate is a pivotal oncometabolite in the TME that drives macrophage M2
      polarization to promote breast cancer proliferation, migration, and angiogenesis.
      In addition, we identified that the activation of ERK/STAT3, major signaling
      molecules in the lactate signaling pathway, deepens our molecular understanding
      of how lactate educates TAMs. Moreover, suppression of ERK/STAT3 signaling
      diminished tumor growth and angiogenesis by abolishing lactate-induced M2
      macrophage polarization. Finally, research data of the natural compound
      withanolide D provide evidence for ERK/STAT3 signaling as a potential therapeutic
      strategy for the prevention and treatment of breast cancer. These findings
      suggest that the lactate-ERK/STAT3 signaling pathway is a driver of breast cancer
      progression by stimulating macrophage M2-like polarization and reveal potential
      new therapeutic targets for breast cancer treatment.

PMID- 29468931
TI  - Rituximab is an acceptable alternative to ocrelizumab for treating multiple
      sclerosis - No.

PMID- 29468932
TI  - Identification and location tasks rely on different mental processes: a diffusion
      model account of validity effects in spatial cueing paradigms with emotional
      stimuli.
AB  - Spatial cueing paradigms are popular tools to assess human attention to emotional
      stimuli, but different variants of these paradigms differ in what participants'
      primary task is. In one variant, participants indicate the location of the target
      (location task), whereas in the other they indicate the shape of the target
      (identification task). In the present paper we test the idea that although these
      two variants produce seemingly comparable cue validity effects on response times,
      they rest on different underlying processes. Across four studies (total N = 397;
      two in the supplement) using both variants and manipulating the motivational
      relevance of cue content, diffusion model analyses revealed that cue validity
      effects in location tasks are primarily driven by response biases, whereas the
      same effect rests on delay due to attention to the cue in identification tasks.
      Based on this, we predict and empirically support that a symmetrical distribution
      of valid and invalid cues would reduce cue validity effects in location tasks to
      a greater extent than in identification tasks. Across all variants of the task,
      we fail to replicate the effect of greater cue validity effects for arousing (vs.
      neutral) stimuli. We discuss the implications of these findings for best practice
      in spatial cueing research.

PMID- 29468933
TI  - Endocrinology and Pediatric Exercise Science-The Year That Was 2017.
AB  - The Pediatric Exercise Science "Year That Was" section aims to highlight the most
      important (to the author's opinion) manuscripts that were published in 2017 in
      the field of endocrinology and pediatric exercise science. This year's selection
      includes studies showing that 1) in pubertal swimmers, there is a decrease in
      insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) during
      intense training (a catabolic-type hormonal response) with an anabolic "rebound"
      characterized by a significant increase of these growth factors during training
      tapering down. Moreover, it was shown that changes of IGF-I and IGFBP-3
      paralleled changes in peak and average force but not with endurance properties,
      showing decreases during intense training and increases during tapering; 2) a
      meta-analysis showing that growth hormone administration elicits significant
      changes in body composition and possible limited effect on anaerobic performance
      but does not increase either muscle strength or aerobic exercise capacity in
      healthy, young subjects; and 3) short-term exercise intervention can prevent the
      development of polycystic ovary syndrome in a dose-dependent manner in letrozole
      induced polycystic ovary syndrome rat model with high-intensity exercise being
      most effective. The implication of these studies to the pediatric population,
      their importance, and the new research avenues that were opened by these studies
      is emphasized.

PMID- 29468934
TI  - Impact of a Pharmacist-Provided Spirometry Service on Access to Results in a
      Primary Care Setting.
AB  - OBJECTIVES: The primary objective of this study was to determine the effect of a
      pharmacist-provided spirometry service within a federally qualified health center
      on the percentage of spirometry referrals completed with results reviewed by the
      ordering provider. Secondary objectives evaluated differences between internal
      and external referrals, medication recommendations made by the pharmacist, and
      revenue brought in by the service. METHODS: Chart reviews were completed to
      determine the referral completion rates between patients who received a
      spirometry referral before (December 2014-September 2015) and after (January 2016
      October 2016) the implementation of the pharmacy-provided spirometry service.
      Chart reviews were also used to determine the number and completion rate among
      referrals for internal and external services in the postimplementation time
      frame. Chart reviews also assessed medication recommendations made by the
      pharmacist. RESULTS: The results demonstrate an increase in referral completion
      rate from 38.1% to 47.0% ( P = .08) between the pre- and postimplementation time
      frames. In the postimplementation time frame, there was a statistically
      significant difference in the percentage of referrals completed between in-house
      referrals and external referrals (70.0% and 40.9%, respectively, P = .0004).
      Comparing clinics with and without the spirometry service, there was a
      statistically significant difference in the total number of spirometry referrals
      (1.13% and 0.59%, respectively, P < .0001) and the percent of referrals completed
      (0.55% and 0.27%, respectively, P = .0002). CONCLUSION: The results suggest that
      offering spirometry within the primary care setting helps to increase the rate of
      completed spirometry tests with results available to the primary care provider.
      Additionally, the results show that there is an increased completion rate in
      patients who receive an internal spirometry referral, which may be due to reduced
      barriers in obtaining this testing. Overall, these results demonstrate that
      providing spirometry in the primary care setting helps to increase spirometry
      results obtained and could be beneficial in other primary care settings.

PMID- 29468935
TI  - Changes in hemodynamic classification over time are common in systemic sclerosis
      associated pulmonary hypertension: insights from the PHAROS cohort.
AB  - Group classification of pulmonary hypertension (PH) is based on pulmonary artery
      wedge pressure (PAWP) on right heart catheterization (RHC). How hemodynamics,
      particularly PAWP, change over time in systemic sclerosis (SSc)-PH patients is
      unknown. SSc-PH patients enrolled in the prospective observational PHAROS
      registry who had > 1 RHC (n = 120) were included in this analysis. Patients were
      considered to have a "PAWP class change" if they had a PAWP <= 15 mmHg on RHC-1
      and then a PAWP > 15 on RHC-2 or had a PAWP > 15 on RHC-1 and then PAWP <= 15 on
      RHC-2. There was a median time of 1.4 years between RHC-1 and RHC-2 and 75% of
      patients had a PH medication added after their initial RHC. PAWP increased
      significantly (11 +/- 5 versus 13 +/- 6 mmHg, P = 0.01) between RHC-1 and RHC-2,
      particularly for patients who were started on PH medications. Overall, 30% of
      patients who had a repeat RHC experienced a PAWP class change between their
      initial and follow-up RHC, independent of whether a PH medication was added.
      Patients initially classified as World Health Organization group 2 PH were most
      likely to change PAWP class over time. In conclusion, PAWP values commonly change
      to a significant degree in SSc-PH, which highlights the challenges in using a
      single time-point PAWP to define clinical classification groups.

PMID- 29468937
TI  - Evaluation of menthol per se on acute perceptions and behavioral choice of
      cigarettes differing in nicotine content.
AB  - Subjective perceptions and self-administration of cigarettes are each influenced
      by nicotine. Yet, differences specifically due to menthol in perceptions and
      choice of cigarettes varying in nicotine, and the association between these
      responses, have not been directly tested. Using a mixed between- and within
      subjects design, acute responses to each of two menthol or non-menthol Spectrum
      research cigarettes, moderate (16-17 mg/g) versus very low (0.4 mg/g) in nicotine
      contents, were compared following brief abstinence in adult smokers preferring
      menthol ( n=44) or non-menthol ( n=29) brands. To ensure reliable perceptions,
      they experienced five exposures to each cigarette, then chose between them. All
      perceptions and choices were greater for moderate vs very low nicotine, as
      expected, and the magnitude of difference in four of six perceptions was
      associated with subsequently greater choice of the moderate nicotine cigarette.
      Importantly, virtually no differences were found between menthol and non-menthol,
      as nearly all perceptions, cigarette choices, and the association between
      perceptions and choice were not moderated by menthol or the interaction of
      nicotine by menthol. Our results indicate perceptions and reinforcement from
      cigarettes do not differ due to menthol when nicotine content and smoking
      topography are carefully controlled. Thus, regardless of menthol, smoking
      perceptions directly predict self-administration behavior.

PMID- 29468938
TI  - Latin American social medicine across borders: South-South cooperation and the
      making of health solidarity.
AB  - Latin American social medicine efforts are typically understood as national
      endeavours, involving health workers, policymakers, academics, social movements,
      unions, and left-wing political parties, among other domestic actors. But Latin
      America's social medicine trajectory has also encompassed considerable between
      country solidarity, building on early twentieth century interchanges among a
      range of players who shared approaches for improving living and working
      conditions and instituting protective social policies. Since the 1960s, Cuba's
      country-to-country solidarity has stood out, comprising medic exchanges,
      training, and other forms of support for the health and social struggles of
      oppressed peoples throughout Latin America and around the world, recently via
      Mision Barrio Adentro in Venezuela. These efforts strive for social justice
      oriented health cooperation based on horizontal power relations, shared political
      values, a commitment to social and economic redistribution, bona fide equity, and
      an understanding of the societal determination of health that includes, but goes
      well beyond, public health and medical care. With Latin America's left-wing surge
      now receding, this article traces the provenance, dynamics, impact, challenges,
      and legacy of health solidarity across Latin American borders and its prospects
      for continuity.

PMID- 29468939
TI  - Objectively measuring pain using facial expression: is the technology finally
      ready?
AB  - Currently, clinicians observe pain-related behaviors and use patient self-report
      measures in order to determine pain severity. This paper reviews the evidence
      when facial expression is used as a measure of pain. We review the literature
      reporting the relevance of facial expression as a diagnostic measure, which
      facial movements are indicative of pain, and whether such movements can be
      reliably used to measure pain. We conclude that although the technology for
      objective pain measurement is not yet ready for use in clinical settings, the
      potential benefits to patients in improved pain management, combined with the
      advances being made in sensor technology and artificial intelligence, provide
      opportunities for research and innovation.

PMID- 29468936
TI  - COPD as an endothelial disorder: endothelial injury linking lesions in the lungs
      and other organs? (2017 Grover Conference Series).
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by chronic
      expiratory airflow obstruction that is not fully reversible. COPD patients
      develop varying degrees of emphysema, small and large airway disease, and various
      co-morbidities. It has not been clear whether these co-morbidities share common
      underlying pathogenic processes with the pulmonary lesions. Early research into
      the pathogenesis of COPD focused on the contributions of injury to the
      extracellular matrix and pulmonary epithelial cells. More recently, cigarette
      smoke-induced endothelial dysfunction/injury have been linked to the pulmonary
      lesions in COPD (especially emphysema) and systemic co-morbidities including
      atherosclerosis, pulmonary hypertension, and chronic renal injury. Herein, we
      review the evidence linking endothelial injury to COPD, and the pathways
      underlying endothelial injury and the "vascular COPD phenotype" including: (1)
      direct toxic effects of cigarette smoke on endothelial cells; (2) generation of
      auto-antibodies directed against endothelial cells; (3) vascular inflammation;
      (4) increased oxidative stress levels in vessels inducing increases in lipid
      peroxidation and increased activation of the receptor for advanced glycation end
      products (RAGE); (5) reduced activation of the anti-oxidant pathways in
      endothelial cells; (6) increased endothelial cell release of mediators with
      vasoconstrictor, pro-inflammatory, and remodeling activities (endothelin-1) and
      reduced endothelial cell expression of mediators that promote vasodilation and
      homeostasis of endothelial cells (nitric oxide synthase and prostacyclin); and
      (7) increased endoplasmic reticular stress and the unfolded protein response in
      endothelial cells. We also review the literature on studies of drugs that inhibit
      RAGE signaling in other diseases (angiotensin-converting enzyme inhibitors and
      angiotensin receptor blockers), or vasodilators developed for idiopathic
      pulmonary arterial hypertension that have been tested on cell culture systems,
      animal models of COPD, and/or smokers and COPD patients.

PMID- 29468940
TI  - Phone coaching in Dialectical Behavior Therapy: frequency and relationship to
      client variables.
AB  - Telephone coaching is a treatment mode in Dialectical Behavior Therapy (DBT) that
      is designed to help clients generalize skills, prevent suicidal behaviors, and
      repair therapeutic ruptures. To date, phone coaching has received scant empirical
      investigation. The aims of this study were to (1) describe patterns in frequency
      of telephone calls and text messaging in DBT and (2) investigate whether
      demographic factors, baseline severity, suicidal behaviors, and therapeutic
      alliance are associated with phone and text frequency. Participants were 51
      adults (35 treatment completers) with borderline personality disorder (BPD) in a
      six-month comprehensive DBT treatment program. Phone coaching frequency was
      documented by therapist weekly session notes. The average number of contacts per
      month was 2.55 (SD = 4.49). Four of the 35 treatment completers comprised 56% of
      the contacts. Having a recent history of suicidal behaviors, degree of severity
      at baseline, or the strength of the therapeutic alliance was not associated with
      phone coaching use. However, lower income was significantly associated with a
      higher frequency of phone coaching use. These preliminary results can help
      clinicians and administrators make informed decisions on how to better provide
      phone coaching and clarify the degree of effort involved in providing this
      service to clients with BPD.

PMID- 29468942
TI  - Perceptions of Determinants of Condom Use Behaviors Among Male Clients of Female
      Sex Workers in Indonesia: A Qualitative Inquiry.
AB  - This study aimed to explore perceived determinants of condom use behaviors among
      male clients of female commercial sex workers (FCSWs) in Belu and Malaka
      districts, Indonesia. One-on-one in-depth interviews guided by the Health Belief
      Model (HBM) were used to collect the data from participants ( n = 42). The
      Framework analysis for qualitative data was employed to analyze the data. Results
      demonstrated several factors associated with lack of and inconsistent condom use
      among the participants. They included self-perceived risk of contracting HIV
      infection, knowledge of the severity of HIV illness and its impacts, and condom
      use: its benefits and its influencing factors. Additionally, factors including
      reduced sexual pleasure and the lack of knowledge of how and where to access
      condoms were important perceived barriers to condom use among participants.
      Having seen images of HIV-/AIDS-positive people, knowing friends and relatives
      suffering from HIV, and knowing FCSWs as a high-risk group for HIV infection were
      the cues to using condoms among several participants. Likewise, self-efficacy was
      also associated with condom use behaviors among the participants. The findings
      indicate the needs for HIV/AIDS interventions that include dissemination of
      HIV/AIDS knowledge, condom promotion, and improvement in the availability of
      condoms for both FCSWs and their clients.

PMID- 29468943
TI  - The informative error: A framework for the construction of individualized
      phenotypes.
AB  - For the goal of individualized medicine, it is critical to have clinical
      phenotypes at hand which represent the individual pathophysiology. However, for
      most of the utilized phenotypes, two individuals with the same phenotype
      assignment may differ strongly in their underlying biological traits. In this
      paper, we propose a definition for individualization and a corresponding
      statistical operationalization, delivering thereby a statistical framework in
      which the usefulness of a variable in the meaningful differentiation of
      individuals with the same phenotype can be assessed. Based on this framework, we
      develop a statistical workflow to derive individualized phenotypes, demonstrating
      that under specific statistical constraints the prediction error of prediction
      scores contains information about hidden biological traits not represented in the
      modeled phenotype of interest, allowing thereby internal differentiation of
      individuals with the same assigned phenotypic manifestation. We applied our
      procedure to data of the population-based Study of Health in Pomerania to
      construct a refined definition of obesity, demonstrating the utility of the
      definition in prospective survival analyses. Summarizing, we propose a framework
      for the individualization of phenotypes aiding personalized medicine by shifting
      the focus in the assessment of prediction models from the model fit to the
      informational content of the prediction error.

PMID- 29468944
TI  - Estimating cost-effectiveness from claims and registry data with measured and
      unmeasured confounders.
AB  - The analysis of observational data to determine the cost-effectiveness of medical
      treatments is complicated by the need to account for skewness, censoring, and the
      effects of measured and unmeasured confounders. We quantify cost-effectiveness as
      the Net Monetary Benefit (NMB), a linear combination of the treatment effects on
      cost and effectiveness that denominates utility in monetary terms. We propose a
      parametric estimation approach that describes cost with a Gamma generalized
      linear model and survival time (the canonical effectiveness variable) with a
      Weibull accelerated failure time model. To account for correlation between cost
      and survival, we propose a bootstrap procedure to compute confidence intervals
      for NMB. To examine sensitivity to unmeasured confounders, we derive simple
      approximate relationships between naive parameters, assuming only measured
      confounders, and the values those parameters would take if there was further
      adjustment for a single unmeasured confounder with a specified distribution. A
      simulation study shows that the method returns accurate estimates for treatment
      effects on cost, survival, and NMB under the assumed model. We apply our method
      to compare two treatments for Stage II/III bladder cancer, concluding that the
      NMB is sensitive to hypothesized unmeasured confounders that represent smoking
      status and personal income.

PMID- 29468941
TI  - The serotonin hypothesis in pulmonary hypertension revisited: targets for novel
      therapies (2017 Grover Conference Series).
AB  - Increased synthesis of serotonin and/or activity of serotonin in pulmonary
      arteries has been implicated in the pathobiology of pulmonary arterial
      hypertension (PAH). The incidence of PAH associated with diet pills such as
      aminorex, fenfluramine, and chlorphentermine initially led to the "serotonin
      hypothesis of pulmonary hypertension." Over the last couple of decades there has
      been an accumulation of convincing evidence that targeting serotonin synthesis or
      signaling is a novel and promising approach to the development of novel therapies
      for PAH. Pulmonary endothelial serotonin synthesis via tryptophan hydroxlase 1
      (TPH1) is increased in patients with PAH and serotonin can act in a paracrine
      fashion on underlying pulmonary arterial smooth muscle cells (PASMCs), In humans,
      serotonin can enter PASMCs via the serotonin transporter (SERT) or activate the 5
      HT1B receptor; 5-HT1B activation and SERT activity cooperate to induce PASMC
      contraction and proliferation via activation of downstream proliferative and
      contractile signaling pathways. Here we will review the current status of the
      serotonin hypothesis and discuss potential and novel therapeutic targets.

PMID- 29468945
TI  - A novel identification approach for discovery of 5-HydroxyTriptamine 2A
      antagonists: combination of 2D/3D similarity screening, molecular docking and
      molecular dynamics.
AB  - 5-HydroxyTriptamine 2A antagonists are potential targets for treatment of various
      cerebrovascular and cardiovascular disorders. In this study, we have developed
      and performed a unique screening pipeline for filtering ZINC database compounds
      on the basis of similarities to known antagonists to determine novel small
      molecule antagonists of 5-HydroxyTriptamine 2A. The screening pipeline is based
      on 2D similarity, 3D dissimilarity and a combination of 2D/3D similarity. The
      shortlisted compounds were docked to a 5-HydroxyTriptamine 2A homology-based
      model, and complexes with low binding energies (287 complexes) were selected for
      molecular dynamics (MD) simulations in a lipid bilayer. The MD simulations of the
      shortlisted compounds in complex with 5-HydroxyTriptamine 2A confirmed the
      stability of the complexes and revealed novel interaction insights. The receptor
      residues S239, N343, S242, S159, Y370 and D155 predominantly participate in
      hydrogen bonding. pi-pi stacking is observed in F339, F340, F234, W151 and W336,
      whereas hydrophobic interactions are observed amongst V156, F339, F234, V362,
      V366, F340, V235, I152 and W151. The known and potential antagonists shortlisted
      by us have similar overlapping molecular interaction patterns. The 287 potential
      5-HydroxyTriptamine 2A antagonists may be experimentally verified.

PMID- 29468947
TI  - Rituximab is an acceptable alternative to ocrelizumab for treating multiple
      sclerosis - Commentary.

PMID- 29468946
TI  - Design, implementation, and interpretation of amplification studies for prion
      detection.
AB  - Amplification assays for transmissible spongiform encephalopathies have been in
      development for close to 15 years, with critical implications for the postmortem
      and antemortem diagnosis of human and animal prion diseases. Little has been
      published regarding the structured development, implementation and interpretation
      of experiments making use of protein misfolding cyclic amplification (PMCA) and
      real time quaking-induced conversion (RT-QuIC), and our goal with this
      Perspectives manuscript is to offer a framework which might allow for more
      efficient expansion of pilot studies into diagnostic trials in both human and
      animal subjects. This framework is made up of approaches common to diagnostic
      medicine, including a thorough understanding of analytical and diagnostic
      sensitivity and specificity, an a priori development of amplification strategy,
      and an effective experimental design. It is our hope that a structured framework
      for prion amplification assays will benefit not only experiments seeking to
      sensitively detect naturally-occurring cases of prion diseases and describe the
      pathogenesis of TSEs, but ultimately assist with future endeavors seeking to use
      these methods more broadly for other protein misfolding disorders, including
      Alzheimer's and Parkinson's disease.

PMID- 29468948
TI  - Preventing Musculoskeletal Disorders in Factory Workers: Evaluating a New Eight
      Minute Stretching Program.
AB  - A preshift stretching program was implemented to evaluate its effectiveness in
      preventing work-related musculoskeletal disorders (WMSD). Workers in a Midwestern
      factory were assessed for WMSDs before and after the new 8-min stretching program
      was implemented. Aggregate WMSD data were evaluated and sick days used from the
      start of the new program were compared with the same 60-day period the previous
      year. Potential cost savings were also assessed. The researchers found a
      significant decline in injury rates and time-off requests. Cost savings were
      noted for both the employer and employees. Additional studies with more workers,
      as well as longitudinal designs are recommended to verify the findings in this
      program evaluation study.

PMID- 29468949
TI  - Methodologies for Investigating Performance Changes With Supplement Use.
AB  - Many expert sporting bodies now support a pragmatic acceptance of the use of
      performance supplements which have passed a risk:benefit analysis of being safe,
      effective, and permitted for use, while also being appropriate to the athlete's
      age and maturation in their sport. However, gaining evidence of the performance
      benefits of these supplements is a process challenged by the scarcity of research
      in relation to the number of available products, and the limitations of the poor
      quality of some studies. While meta-analyses and systematic reviews can help to
      provide information about the general use of performance supplements, the
      controlled scientific trial provides the basis on which these reviews are
      undertaken, as well as an opportunity to address more specific questions about
      supplement applications. Guidelines for the design of studies include the choice
      of well-trained athletes who are familiarized with performance tasks that have
      been chosen on their basis of their known reliability and validity. Supplement
      protocols should be chosen to maximize the likely benefits, and researchers
      should also make efforts to control confounding variables, while keeping
      conditions similar to real-life practices. Performance changes should be
      interpreted in light of what is meaningful to the outcomes of sporting
      competition. Issues that have been poorly addressed to date include the use of
      several supplements in combination and the use of the same supplement over
      successive events, both within a single, and across multiple competition days.
      Strategies to isolate and explain the variability of benefits to individuals are
      also a topic for future investigation.

PMID- 29468950
TI  - T3SS effectors in Vibrios: Homology in sequence, diversity in biological
      functions?

PMID- 29468952
TI  - Rituximab is an acceptable alternative to ocrelizumab for treating multiple
      sclerosis - Yes.

PMID- 29468951
TI  - Cost-effectiveness thresholds: methods for setting and examples from around the
      world.
AB  - INTRODUCTION: Cost-effectiveness thresholds (CETs) are used to judge if an
      intervention represents sufficient value for money to merit adoption in
      healthcare systems. The study was motivated by the Brazilian context of HTA,
      where meetings are being conducted to decide on the definition of a threshold.
      Areas covered: An electronic search was conducted on Medline (via PubMed), Lilacs
      (via BVS) and ScienceDirect followed by a complementary search of references of
      included studies, Google Scholar and conference abstracts. Cost-effectiveness
      thresholds are usually calculated through three different approaches: the
      willingness-to-pay, representative of welfare economics; the precedent method,
      based on the value of an already funded technology; and the opportunity cost
      method, which links the threshold to the volume of health displaced. An explicit
      threshold has never been formally adopted in most places. Some countries have
      defined thresholds, with some flexibility to consider other factors. An implicit
      threshold could be determined by research of funded cases. Expert commentary:
      CETs have had an important role as a 'bridging concept' between the world of
      academic research and the 'real world' of healthcare prioritization. The
      definition of a cost-effectiveness threshold is paramount for the construction of
      a transparent and efficient Health Technology Assessment system.

PMID- 29468953
TI  - Socioeconomic differences in the use of alcohol and drunkenness in adolescents:
      Trends in the Health Behaviour in School-aged Children study in Finland 1990
      2014.
AB  - AIMS: The aims of this study were to explore time-based trends of socioeconomic
      differences in alcohol use and drunkenness in Finnish adolescents from 1990 to
      2014 and to investigate the significance of two indicators in detecting
      socioeconomic differences in alcohol use and drunkenness. METHODS: Data were
      retrieved from seven surveys conducted as part of the Health Behaviour in School
      aged Children (HBSC) study in Finland from 1990 to 2014. The alcohol use and
      drunkenness of 15-year-old students, as well as socioeconomic status, including
      educational aspiration and perceived family wealth, were assessed via a self
      report questionnaire. Logistic regression models were used to investigate the
      relationships between alcohol use, drunkenness and indicators of socioeconomic
      status. RESULTS: The study showed that the alcohol use and drunkenness of Finnish
      15-year-old adolescents have decreased since the late 1990s. However, the level
      of decrease is not consistent among different socioeconomic groups and
      socioeconomic differences in drinking behaviour between two educational
      aspiration groups have persisted over two decades. Girls from the groups with low
      perceived family wealth were more likely to be frequently drunk in the time
      period 2006-2014. CONCLUSIONS: This study suggests that students with low
      educational aspiration should be the target population for interventions aiming
      at reducing the alcohol use and drunkenness of Finnish adolescents. In future
      interventions aimed at reducing heavier drinking, adolescents (especially girls)
      from less wealthy families should be the first priority. Further studies on
      trends in socioeconomic differences in alcohol use and drunkenness in adolescence
      should be conducted using different indicators of socioeconomic status and other
      social context factors should also be taken into account.

PMID- 29468954
TI  - Reducing social inequalities in health: Moving from the 'causes of the causes' to
      the 'causes of the structures'.

PMID- 29468955
TI  - Construction of Antibacterial Surface Via Layer-by-Layer Method.
AB  - Construction of antibacterial surfaces or films is of great interest in various
      fields including biomedicine, food, agriculture and so on. So far, a number of
      antibacterial agents have been used to construct antibacterial surfaces. Layer-by
      Layer (LbL) assembly is a simple and versatile deposition process for fabricating
      multilayer thin films with great advantages to control the architecture and
      composition of the films. In this review, we give a brief introduction of LbL,
      and different materials used to fabricate antibacterial surfaces with LbL
      assembly approach are described as well as their drawbacks. Much attention is
      also paid to the recent development of multifunctional and intelligent
      antibacterial surfaces. Moreover, the advantages and limitations of these
      different types of antibacterial materials are summarized and subsequently
      directions for future development are proposed.

PMID- 29468956
TI  - Antibacterial Metal Oxide Nanoparticles: Challenges in Interpreting the
      Literature.
AB  - Metal oxide nanoparticles (MO-NPs) are known to effectively inhibit the growth of
      a wide range of Gram-positive and Gram-negative bacteria. They have emerged as
      promising candidates to challenge the rising global issue of antimicrobial
      resistance. However, a comprehensive understanding of their mechanism of action
      and identifying the most promising NP materials for future clinical translation
      remain a major challenge due to variations in NP preparation and testing methods.
      With various types of MO-NPs being rapidly developed, a robust, standardized, in
      vitro assessment protocol for evaluating the antibacterial potency and efficiency
      of these NPs is needed. Calculating the number of NPs that actively interact with
      each bacterial cell is critical for assessing the dose response for toxicity.
      Here we discuss methods to evaluate MO-NPs antibacterial efficiency with focus on
      issues related to NPs in these assays. We also highlight sources of experimental
      variability including NP preparation, initial bacterial concentration, bacterial
      strains tested, culture microenvironment, and reported dose.

PMID- 29468957
TI  - Antibacterial Coatings Based on Chitosan for Pharmaceutical and Biomedical
      Applications.
AB  - The risk of bacterial colonization of abiotic surfaces of biomedical devices
      poses important challenges for the pharmaceutical and biomaterials science
      fields. In this scenario, antibacterial coatings have been developed, using a
      number of different molecules and materials. Among them, chitosan is a non
      cytotoxic, biocompatible biopolymer with an inherent antimicrobial activity that
      has been already used in a wide variety of healthcare and industrial
      applications. Herein, chitosan-based antibacterial coatings are critically
      surveyed, with a special emphasis on their production methods, pharmaceutical and
      biomedical applications, along with their pros and cons, and finally highlighting
      the key challenges to be faced and future perspectives in this field.

PMID- 29468958
TI  - Impact of Pre-procedural Cerebrovascular Events on Clinical Outcomes After
      Transcatheter Aortic Valve Implantation in Patients with Severe Aortic Stenosis.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an increasingly
      common treatment of symptomatic severe aortic valve stenosis (AS). Thus, it is
      reasonable to carefully investigate the impact of individual clinical factors on
      outcomes after TAVI. OBJECTIVES: We aimed to investigate the impact of the
      previous cerebro-vascular events (CVEs) on outcomes of patients with severe AS
      undergoing TAVI. METHODS: A total of 148 consecutive patients scheduled for TAVI
      were included and stratified as with and without a history of CVEs (stroke or
      transient ischemic attack). Frailty features were also assessed. The primary
      endpoint was a 12-month all-cause mortality. RESULTS: Seventeen (11.5%) patients
      had a history of CVEs (the CVE group). At 30 days and 12 months, all-cause
      mortality was higher in the CVE group [30-day: 5 (29.4%) vs. 7 (5.3%); p=0.005;
      12-month: 9 (52.9%) vs. 13 (9.9%); p=0.001]. Similarly, at the longest available
      follow-up, mortality was higher in the CVE group [10 (58.8%) vs. 23 (17.6%);
      p=0.001]. Similar rates of other complications after TAVI were noted, apart from
      inhospital acute kidney injury (AKI) grade 3 [3 (17.6%) vs. 5 (3.8%); p=0.049]
      and blood transfusions [9 (52.9%) vs. 35 (26.7%); p=0.026]. Results of 5MWT and
      Katz index assessment indicated a greater level of frailty in the CVE group.
      There were no differences in subsequent events including CVEs, bleeding,
      myocardial infarction, and new-onset of atrial fibrillation (AF) at 12 months
      between the groups. CONCLUSION: We showed that a history of CVEs in patients with
      severe AS undergoing TAVI is associated with a higher long-term mortality.

PMID- 29468959
TI  - In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on
      Possible Correlation.
AB  - AIM AND OBJECTIVE: Lipoxygenase (LOX) enzymes play an important role in the
      pathophysiology of several inflammatory and allergic diseases including bronchial
      asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid
      arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are
      believed to be an ideal approach in the treatment of diseases caused by its over
      expression. In this regard, several synthetic and natural agents are under
      investigation worldwide. Alkaloids are the most thoroughly investigated class of
      natural compounds with outstanding past in clinically useful drugs. In this
      article, we have discussed various alkaloids of plant origin that have already
      shown lipoxygenase inhibition in-vitro with possible correlation in in silico
      studies. MATERIALS AND METHODS: Molecular docking studies were performed using
      MOE (Molecular Operating Environment) software. Among the ten reported LOX
      alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed
      excellent docking scores and receptor sensitivity. RESULT AND CONCLUSION: These
      compounds already exhibited in vitro lipoxygenase inhibition and the MOE results
      strongly correlated with the experimental results. On the basis of these in vitro
      assays and computer aided results, we suggest that these compounds need further
      detail in vivo studies and clinical trial for the discovery of new more effective
      and safe lipoxygenase inhibitors. In conclusion, these results might be useful in
      the design of new and potential lipoxygenase (LOX) inhibitors.

PMID- 29468960
TI  - The Discovery of Antibacterial Natural Compound Based on Peptide Deformylase.
AB  - BACKGROUND: In recent years, Staphylococcus aureus have developed resistance to
      medicines used for the treatment of human infections. Therefore, the search for
      antibacterial agents of high potency against Staphylococcus aureus is of great
      concern. Peptide deformylase (PDF), a metalloprotease catalyzing the removal of a
      formyl group from newly synthesized proteins, has been considered to be an
      important antibacterial drug target. OBJECTIVE: To discover novel antibacterial
      drugs based on Staphylococcus aureus peptide deformylase. METHOD: PDF-based
      virtual screening of compounds from Traditional Chinese Medicine Database@Taiwan
      was performed by Sybyl X2.1 Surflex dock software. Compounds which possess high
      docking score were used for the following antibacterial experiments to evaluate
      their antibacterial activities. Kanamycin was also used in the antibacterial
      experiment as a control substance in the assay. Furthermore, molecular docking
      studies was applied to elucidate binding interaction between some compounds and
      PDF. In silico pharmacokinetic and toxicity prediction was explored to explain
      the reasons why these compounds might stand good chance of providing some
      pharmaceutical benefits. RESULTS: Gentiopicroside, protosappanin B,
      dihydromyricetin and cryptochlorogenic acid with high docking score were used for
      our subsequent antibacterial assays. The Minimum Inhibitory Concentration (MIC)
      of kanamycin and gentiopicroside were 0.008 mg.mL-1 and 0.431 mg.mL-1,
      respectively, other three compounds, protosappanin B, dihydromyricetin and
      cryptochlorogenic acid have close MIC value of 0.50 mg.mL-1. CONCLUSION:
      Dihydromyricetin, with the MIC value of 0.50 mg.mL-1 and relatively high drug
      score of 0.82, may serve as a novel antibacterial lead compound.

PMID- 29468961
TI  - A Green Synthesis of Xanthenone Derivatives in Aqueous Media Using TiO2-CNTs
      Nanocomposite as an Eco-Friendly and Re-Usable Catalyst.
AB  - AIM AND OBJECTIVE: The xanthene (dibenzopyran) framework constitutes the core
      structure of many biologically active compounds, that they have been of interest
      because of their pharmacological activities like antiviral, antibacterial, anti
      inflammatory, and CCR1 antagonist. As heterogeneous catalysts offer several
      advantages over homogeneous catalysts, the performance of reactions on the
      surface of nanosized heterogeneous salts has received a great deal of interest in
      recent years. In the area of nanosized heterogeneous catalysts there is a
      noticeable range of reactions that are catalyzed efficiently by TiO2 NPs.
      Moreover, carbon nanotubes (CNTs) as a support can be used to obtain
      nanoparticles with modified morphology, structural, chemical, electrical, and
      optical properties. The catalytic activity of titanium dioxide supported on
      carbon nanotubes has been greatly improved. MATERIALS AND METHODS: The present
      methodology focus on the synthesis of 7,7-dimethyl-10-aryl- 6,7,8,10-tetrahydro
      9H-[1,3]dioxolo[4,5-b]xanthen-9-ones, through a condensation reaction of
      dimedone, aromatic aldehydes and 3,4-methylenedioxyphenol, using a catalytic
      amount of TiO2- CNTs nanocomposite (15 mol%) at 80 C in aqueous media, within 60
      90 min. The TiO2-CNTs nanocomposite was also prepared by a known simple
      sonochemical method. RESULTS: A series of 7,7-dimethyl-10-aryl-6,7,8,10
      tetrahydro-9H-[1,3]dioxolo[4,5-b]xanthen-9-ones were successfully synthesized in
      high yields (92-98%). All synthesized compounds were well characterized by their
      satisfactory elemental analyses, IR, 1H and 13C NMR spectroscopy. The synthesized
      catalyst was fully characterized by SEM, TEM, XRD, and EDX techniques.
      CONCLUSION: In summary, this investigation constitutes a novel and efficient
      route for the synthesis of 7,7-dimethyl-10-aryl-6,7,8,10-tetrahydro-9H
      [1,3]dioxolo[4,5-b]xanthen-9-ones in high yields, by a three-component reaction
      of dimedone, aromatic aldehydes and 3,4-methylenedioxyphenol in water and in the
      presence of the TiO2-CNTs nanocomposite as a green, effective and recyclable
      catalyst. This novel method has the advantages of high yields, mild reaction
      conditions, short reaction time, easy work-up, inexpensive reagents and
      environmentally friendly procedure.

PMID- 29468962
TI  - Plant-Derived Polyphenols in Human Health: Biological Activity, Metabolites and
      Putative Molecular Targets.
AB  - BACKGROUND: Hibiscus sabdariffa, Lippia citriodora, Rosmarinus officinalis and
      Olea europaea, are rich in bioactive compounds that represent most of the
      phenolic compounds' families and have exhibited potential benefits in human
      health. These plants have been used in folk medicine for their potential
      therapeutic properties in human chronic diseases. Recent evidence leads to
      postulate that polyphenols may account for such effects. Nevertheless, the
      compounds or metabolites that are responsible for reaching the molecular targets
      are unknown. OBJECTIVE: data based on studies directly using complex extracts on
      cellular models, without considering metabolic aspects, have limited
      applicability. In contrast, studies exploring the absorption process, metabolites
      in the blood circulation and tissues have become essential to identify the
      intracellular final effectors that are responsible for extracts bioactivity. Once
      the cellular metabolites are identified using high-resolution mass spectrometry,
      docking techniques suppose a unique tool for virtually screening a large number
      of compounds on selected targets in order to elucidate their potential
      mechanisms. RESULTS: we provide an updated overview of the in vitro and in vivo
      studies on the toxicity, absorption, permeability, pharmacokinetics and cellular
      metabolism of bioactive compounds derived from the abovementioned plants to
      identify the potential compounds that are responsible for the observed health
      effects. CONCLUSION: we propose the use of targeted metabolomics followed by in
      silico studies to virtually screen identified metabolites on selected protein
      targets, in combination with the use of the candidate metabolites in cellular
      models, as the methods of choice for elucidating the molecular mechanisms of
      these compounds.

PMID- 29468963
TI  - NF-kappaB-IKKbeta Pathway as a Target for Drug Development: Realities, Challenges
      and Perspectives.
AB  - BACKGROUND: Nuclear factor kappaB (NF-kappaB) comprises a family of proteins that
      act as transcription factors promoting the expression of many genes. Activation
      of NF-kappaB biochemical cascades is associated with the regulation of innate and
      adaptive immune responses and inflammation, among other physiological responses.
      However, genetic abnormalities and continuous stimulation of the NF- kappaB
      IKKbeta pathway are directly related to many types of inflammatory and autoimmune
      diseases, as well as to the genesis and survival of tumor cells. OBJECTIVES:
      Inhibition of the NF-kappaB-IKKbeta cascade can be considered an attractive
      therapeutic method for the genesis of new prototypes to combat these chronic
      multifactorial diseases. RESULTS: This review describes some prototypes and drugs
      that act to inhibit the NF-kappaB-IKKbeta pathway, highlighting the realities,
      challenges and perspectives for therapeutic use. CONCLUSION: Although only
      proteasome inhibitors, such as bortezomib and carfilzomib, are a reality as
      therapeutically useful drugs among the known modulators of possible targets in
      the NF-kappaB-IKKbeta pathway, some other prototypes described as IKKbeta
      inhibitors have entered clinical stages as drug candidates for the control of
      inflammatory diseases. It is important to note that some classical drugs
      available on the pharmaceutical market, such as acetylsalicylic acid, were also
      described more recently as NF-kappaB pathway modulators as IKKbeta inhibitors.

PMID- 29468964
TI  - Recent Advances in Antibacterial, Antiprotozoal and Antifungal Trends of Eurycoma
      longifolia: A Review of Therapeutic Implications and Future Prospects.
AB  - BACKGROUND: Eurycoma longifolia (E. longifolia) has gained widespread recognition
      due to its versatile pharmacological activities including aphrodisiac,
      anticancer, antimicrobial, antioxidant, anti-inflammatory, anxiolytic, anti
      diabetic, ergogenic, insecticidal, anti-rheumatism, bone protection, and anti
      ulcer effects. OBJECTIVE: This review was aimed to critically overview the
      literature and summarizes the antibacterial, antiprotozoal, and antifungal trends
      of E. longifolia and its medicinally active components. RESULTS: Besides its well
      documented safety, efficacy, and tolerability, a plethora of in vitro, in vivo,
      and human clinical studies has evidenced the antimicrobial efficacy of E.
      longifolia and its bioactive constituents. Phytochemical screening of various
      types of extracts (methanolic, ethyl acetate, and nbutanolic) from different
      parts (roots, stem, and leaves) of E. longifolia displayed a dose-dependent
      antibacterial, antiprotozoal, and antifungal responses. Comparative analysis
      revealed that the root extract of E. longifolia exhibited the highest
      antimicrobial efficacy compared to other parts of the plant. Bioactivity-guided
      fractionation identified that among all of the medicinal compounds isolated/
      extracted from different parts of E. longifolia, eurycomanone displayed the
      strongest antibacterial, antiprotozoal and antifungal activities. CONCLUSION:
      Based on the critical analysis of the literature, we identified that E.
      longifolia exhibits promising antibacterial, antiprotozoal, and antifungal
      efficacies against various pathogenic microbes and thus can be considered as a
      potential complementary and alternative antimicrobial therapy.

PMID- 29468965
TI  - Versatility of Cancer Associated Fibroblasts: Commendable Targets for Anti-tumor
      Therapy.
AB  - BACKGROUND AND OBJECTIVE: Tumor growth, development, progression, metastasis,
      invasion and resistivity against drugs solely depend on the recruitment of
      surrounding cells, extracellular matrix and Tumor Microenvironment (TME). TME is
      directly as well as indirectly associated with Cancer- Associated Fibroblasts
      (CAF). The interactions of CAF with tumor surrounding cells, their origination,
      activation, transformation and ability to recruit other non-tumor cells for the
      clemency of tumor, are very complex and under active research since long. This
      study provides an in-depth review of CAF and highlights its potential targets for
      the regulation of TME as well as discusses current drugs in clinical trials,
      targeting through CAF. CONCLUSION: The potential role of CAF in anti-tumor
      therapy is based on its coherent response against drugs, targeting different
      tumor sections through these genetically more stable and anti-immunosupportive
      CAF cells. CAF can be targeted through immunity system; Growth Factors (GF)
      including Transforming growth factor (TGF), vascular endothelial GF, fibroblast
      GF, platelet derived GF; and TME elements including hypoxia, carbonic anhydrase,
      extracellular matrix (ECM). Collectively these features of CAF make it most
      vulnerable against single as well as combinational, anti-tumor therapy for
      synergistic or additive effects. Potential activities of CAF, their origination
      mechanisms and identification of meticulous bio-markers are needed to be
      investigated further. The rousing facts about them mutually culminate the
      anticipation of progress towards novel therapeutic establishment against cancer
      through CAFs that are under progressive research at all levels including, pre
      clinical and clinical trials as well as possess much potential to be explored
      further.

PMID- 29468966
TI  - Ultrasound Assisted Synthesis of 3,4-Diyne Substituted Isocoumarin Derivatives:
      Identification of Potential Cytotoxic Agents.
AB  - BACKGROUND: The 3,4-diyne substituted isocoumarins have been designed,
      synthesized and explored as potential anti-proliferative agents. METHOD:
      Ultrasound assisted synthesis of these compounds was carried out by using a three
      step method involving (i) Pd/C-Cu catalyzed cross-coupling between the methyl 2
      iodobenzoate and buta- 1,3-diynylbenzene followed by (ii) I2-mediated
      electrophilic cyclization of the resultant 2-(alk-1- ynyl)benzoate ester and
      (iii) subsequent alkynylation of 4-iodo-3-(phenylethynyl)-isocoumarin under Pd/C
      Cu catalysis. CONCLUSION: The synthesized compounds showed promising growth
      inhibition when tested against MDA-MB 231 and K562 cancer cell lines.

PMID- 29468967
TI  - Recent Advances in Development of Polyphenols as Anticancer Agents.
AB  - Still now, for many forms of the disseminated cancers there is no curative
      therapy available. The discovery of novel active chemotherapeutic agents is
      largely essential to overcome this problem. Natural compounds polyphenols are
      mainly characterized by a huge structural variance; they can render them
      intrinsic dietary components due to their common occurrence in plants. Now-a
      days, polyphenols (secondary metabolites) are characterized by a vast spectrum of
      physiological significance. From the past twenty years in the world of scientific
      research, polyphenols play an important role in a wide range of physiological
      processess. This review focuses on the development of polyphenols as antitumor
      agent in recent research studies.

PMID- 29468968
TI  - Arginine Functionalized Bacterial Cellulose Nanofibers Containing Gel as an
      Effective Wound Dressing: In vitro and In vivo Evaluation.
AB  - BACKGROUND: Nanofibers such as bacterial cellulose nanofibers (BC-NFs) have
      gained increasing attention for use in wound dressings. Topical application of
      arginine can stimulate wound healing significantly. OBJECTIVE: In order to
      promote the wound healing process, arginine functionalized BC-NFs containing gel
      (Arg-BC-NFs gel) was prepared by the electrostatic attachment of arginine on the
      surface of BCNFs. METHOD: The effect of pH was evaluated on the amount of the
      attached arginine on the BC-NFs surface. The attachment of arginine on BC-NFs
      surface was investigated by FTIR spectroscopy. The morphology of Arg-BC-NFs was
      evaluated using FESEM. The viscosity and spreadability of Arg-BC-NFs and the
      release of arginine from Arg-BC-NFs were evaluated. The effectiveness of Arg-BC
      NFs gel was assessed in a full thickness wound model in rats. Re-epithelization,
      collagen deposition and neovascularization were investigated in the wound tissues
      using histological and immunohistochemical analysis. RESULTS: FTIR spectra and
      the zeta potential of BC-NFs confirmed the surface modification of BC-NFs by
      arginine. FESEM images showed the nanofibrous structure of Arg-BC-NFs. The
      release of arginine from Arg-BC-NFs gel was in a sustained release manner for 24
      h. The appropriate viscosity and spreadability of Arg-BC-NFs gel confirmed its
      easy topical application. In vivo studies revealed that Arg-BCNFs gel promoted
      wound closure at a faster rate than BC-NFs gel and arginine solution. Moreover,
      faster and more organized re-epithelialization, angiogenesis and collagen
      deposition were achieved in Arg-BC-NFs gel treated group in comparison to other
      groups. CONCLUSION: Arg-BC-NFs gel can be introduced as an effective wound
      dressing for acute wounds.

PMID- 29468969
TI  - RAFTing Towards the Shore of Nanotherapeutic.

PMID- 29468970
TI  - Comparative Genetic Variability in HIV-1 Subtype C vpu Gene in Early Age Groups
      of Infants.
AB  - OBJECTIVE: Identifying the genetic variability in vertically transmitted viruses
      in early infancy is important to understand the disease progression. Being
      important in HIV-1 disease pathogenesis, vpu gene, isolated from young infants
      was investigated to understand the viral characteristics. METHOD: Blood samples
      were obtained from 80 HIV-1 positive infants, categorized in two age groups;
      acute (<6 months) and early (>6-18 months). A total of 77 PCR positive samples,
      amplified for vpu gene, were sequenced and analyzed. RESULTS: 73 isolates
      belonged to subtype C. Analysis of heterogeneity of amino acid sequences in
      infant groups showed that in the sequences of acute age group both insertions and
      deletions were present while in the early age group only deletions were present.
      In the acute age group, a deletion of 3 residues (RAE) in the first alfa helix in
      one sequence and insertions of 1-2 residues (DM, GH, G and H) in the second alfa
      helix in 4 sequences were observed. In the early age group, deletion of 2
      residues (VN) in the cytoplasmic tail region in 2 sequences was observed. Length
      of the amino terminal was observed to be gradually increasing with the increasing
      age of the infants. Protein Variation Effect Analyzer software showed that
      deleterious mutations were more in the acute than the early age group. Entropy
      analysis revealed that heterogeneity of the residues was comparatively higher in
      the sequences of acute than the early age group. CONCLUSION: Mutations observed
      in the helixes may affect the conformation and lose the ability to degrade CD4
      receptors. Heterogeneity was decreasing with the increasing ages of the infants,
      indicating positive selection for robust virion survival.

PMID- 29468971
TI  - IL-10 Promoter -592 Polymorphism may Influence Susceptibility to HIV Infection in
      South Indian Population.
AB  - BACKGROUND: Genetic factors play an important role in the development of disease
      susceptibility or protection. Cytokine gene polymorphisms are reported to be
      associated with altered levels of cytokine production that can impact disease
      progression in HIV and TB. OBJECTIVE: In this study, we studied IL-10 -592(C/A)
      and TGF-beta -509 (C/T) promoter polymorphisms to understand their role in
      susceptibility or resistance to HIV and TB in a South Indian population. METHOD:
      Genomic DNA was isolated from healthy controls, pulmonary tuberculosis patients
      (n=122) and HIV positive individuals (n=100) and used for genotyping by
      polymerase chain reaction followed by restriction fragment length polymorphism
      (PCR-RFLP) method. RESULTS: Results revealed that under dominant model (CC vs
      CA+AA), IL-10 -592 'A' allele either 'CA' or 'AA' combinations significantly
      associated with susceptibility to HIV compared to healthy controls (OR: 1.88(1.05
      3.35); p=0.030). However, we found no significant association with TB. TGF-beta 
      509 polymorphism did not associate with either HIV or TB under overdominant
      model. Neither of the promoter polymorphisms associated with sex in either HIV or
      TB. However, a trend towards higher risk to HIV was found in females compared
      with males in IL-10 -592 'AA' genotype. CONCLUSION: This study suggests the
      association of IL-10 -592 "AA" genotype with susceptibility to HIV under dominant
      model in the Southern Indian population. Future studies are needed with a larger
      sample size in order to confirm the observations made in this study.

PMID- 29468972
TI  - Investigating HIV-Human Interaction Networks to Unravel Pathogenic Mechanism for
      Drug Discovery: A Systems Biology Approach.
AB  - BACKGROUND: Two big issues in the study of pathogens are determining how
      pathogens infect hosts and how the host defends itself against infection.
      Therefore, investigating host-pathogen interactions is important for
      understanding pathogenicity and host defensive mechanisms and treating
      infections. METHODS: In this study, we used omics data, including time-course
      data from high-throughput sequencing, real-time polymerase chain reaction, and
      human microRNA (miRNA) and protein-protein interaction to construct an
      interspecies protein-protein and miRNA interaction (PPMI) network of human CD4+ T
      cells during HIV-1 infection through system modeling and identification. RESULTS:
      By applying a functional annotation tool to the identified PPMI network at each
      stage of HIV infection, we found that repressions of three miRNAs, miR-140-5p,
      miR-320a, and miR-941, are involved in the development of autoimmune disorders,
      tumor proliferation, and the pathogenesis of T cells at the reverse transcription
      stage. Repressions of miR-331-3p and miR-320a are involved in HIV-1 replication,
      replicative spread, anti-apoptosis, cell proliferation, and dysregulation of cell
      cycle control at the integration/replication stage. Repression of miR-341-5p is
      involved in carcinogenesis at the late stage of HIV-1 infection. CONCLUSION: By
      investigating the common core proteins and changes in specific proteins in the
      PPMI network between the stages of HIV-1 infection, we obtained pathogenic
      insights into the functional core modules and identified potential drug
      combinations for treating patients with HIV-1 infection, including thalidomide,
      oxaprozin, and metformin, at the reverse transcription stage; quercetin,
      nifedipine, and fenbendazole, at the integration/replication stage; and
      staurosporine, quercetin, prednisolone, and flufenamic acid, at the late stage.

PMID- 29468973
TI  - Molecular Docking In Formulation And Development.
AB  - In pharmaceutical research drug discovery and development process is time
      consuming and expensive. In many cases, it produces incompetent results due to
      the failure of in vitro and in vivo conventional approaches. Before any new drug
      is placed in the market it must undergo rigorous testing to get FDA approval. Due
      to the several limitations imposed by the drug discovery process, in recent times
      in silico approaches are widely applied in this field. In this review we have
      compiled docking studies which has found it's applications to predict drug
      excipient interactions which in turn assist to increase protein stability; to
      determine enzyme peptide interactions which maybe further used in drug
      development studies; to determine the most stable drug inclusion complex; to
      analyze structure at molecular level that ascertain an increase in solubility,
      dissolution and in turn the bioavailability of the drug; to design a dosage form
      that amplify the drug discovery and development process. The purpose of this
      review is to highlight the current molecular docking strategies used in drug
      discovery and to explore various advances in the field.

PMID- 29468974
TI  - Potentials of PKC in cancer progression and anticancer drug development.
AB  - PKC are a family of serine-threonine kinases which play crucial roles in the
      regulation of important signal transduction pathways in mammalian cell-biology.
      These enzymes are themselves regulated by various molecules that can serve as
      ligands to the regulatory domains and translocate PKC to membrane for activity.
      The role of PKC in the modulation of both proliferative and apoptotic signalling
      in cancer become a subject of intense interest after it was discovered that PKC
      regulates a myriad of enzymes and transcription factors involved in carcinogenic
      signalling. Therefore, PKC has served as an attractive target for the development
      of newer generation of anti-cancer drugs. The following review discusses the
      potential of PKC to be regarded as a target for anti-cancer therapy. We also
      review all the molecules that have been discovered so far to be
      regulators/activators/inhibitors of PKC and also how far these molecules can be
      considered as potential candidates for anti-cancer drug development based on PKC.

PMID- 29468975
TI  - The Protective Effects of Green Tea Catechins in the Management of
      Neurodegenerative Diseases: A Review.
AB  - The therapeutic strategies to manage neurodegenerative diseases remain limited
      and it is necessary to discover new agents for their prevention and control.
      Oxidative stress and inflammation play a main role in the pathogenesis of
      neurodegenerative diseases. Catechins, the major flavonoids in green tea, are
      powerful antioxidants and radical scavengers that possess the potential roles in
      the management of neurodegenerative diseases. Catechins modulate the cellular and
      molecular mechanisms through the inflammation-related NF-kB and the nuclear
      factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Present review
      shows catechins could be effective against neurodegenerative diseases due to
      their antioxidation and anti-inflammation effects and the involved biochemical
      pathways including Nrf2 and NF-kB signaling pathways.

PMID- 29468976
TI  - Toxicity of Biologically Active Peptides and Future Safety Aspects: An Update.
AB  - INTRODUCTION: Peptides are fragments of proteins with significant biological
      activities. These peptides are encoded in the protein sequence. Initially, such
      peptides are inactive in their parental form, unless proteolytic enzymes are
      released. These peptides exhibit various functions and play a therapeutic role in
      the body. OBJECTIVE: Besides the therapeutic and physiological activities of
      peptides, the main purpose of this study was to highlight the safety aspects of
      peptides. METHOD: We performed an organized toxicity and search of available
      literature using PubMed, Google Scholar, Medline, EMBASE, Reaxys and Scopus
      databases. All the relevant citations including research and review articles
      about the toxicity of biologically active peptides were evaluated and gathered in
      this study. RESULT: Biological peptides are widely used in the daily routine
      ranging from food production to the cosmetics industry and also they have a
      beneficial role in the treatment and prevention of different diseases. These
      peptides are manufactured by both chemical and biotechnological techniques, which
      show negligible toxicity, however, some naturally occurring peptides and enzymes
      may induce high toxicity. Depending upon the demand and expected use in the food
      or pharmaceutical industry, we need different approaches to acertain the safety
      of these peptides preferentially through in silico methods. CONCLUSION:
      Intestinal wall disruption, erythrocytes and lymphocytes toxicity, free radical
      production, enzymopathic and immunopathic tissue damage and cytotoxicity due to
      the consumption of peptides are the main problems in the biological system that
      lead to various complicated disorders. Therefore, before considering biologically
      active peptides for food production and for therapeutic purpose, it is first
      necessary to evaluate the immunogenicity and toxicities of peptides.

PMID- 29468977
TI  - The Development of New Factor Xa Inhibitors Based on Amide Synthesis.
AB  - BACKGROUND: Factor Xa (FXa) is known to play a central role in blood coagulation
      cascade and considered to be one of the most attractive targets for oral
      anticoagulants of new generation. OBJECTIVE: Our approach for the development of
      directly acting oral anticoagulants (DOAC), FXa inhibitors was demonstrated in
      this work. METHOD: Chemical synthesis is the base of our approach for the
      development of potential inhibitors. In this work, the substances like R1-(CONH)
      R2-(CONH)-R3 are being developed, using previously described docking and
      screening methods, where R1, R2 and R3 are some chemical groups and (CONH) are
      amide bonds connecting R1, R2 and R3. The direction of amide bond (CONH) could be
      arbitrary for R1, R2 and R2, R3. RESULTS: Chemical modifications were made in the
      frame of the results, taking into account the structure of FXa, chemical
      synthesis capabilities, as well as patentability of the target compounds.
      Subnanomolar potency of several developed compounds was achieved. Several
      analyzers and various testing-suites have been used to measure the concentration
      that doubled the prothrombin time (PTx2). Moreover, in human plasma the PTx2
      concentration of the compound 217 (DD217) turned out to be 80+/-20 nM. The
      compound efficacy has proved by in vivo assays including oral administrations in
      rats, rabbits and monkeys. CONCLUSION: The pharmacodynamic profile of DD217 for
      oral administration in cynomolgus monkeys proves the efficacy of the compound,
      which makes it promising for the future preclinical trials.

PMID- 29468978
TI  - Comparing effectiveness of a combined herbal drug based on Echium amoenum with
      Citalopram in the treatment of Major Depressive Disorder.
AB  - BACKGROUND: According to new studies, only 60% of depressed patients respond to
      pharmaceutical treatment while suffering from their side effects. Natural
      products as adjuvant or alternative therapies should be examined to find safer
      and more effective ways to cope with depression. OBJECTIVE: Finding out the
      potential benefits of a combined herbal drug based on Echium amoenum compared
      with citalopram in the treatment of Major Depressive Disorder. DESIGN AND
      SETTING: In psychiatry clinics of Mashhad University of Medical Sciences, 50
      patients who met the criteria for Major Depressive Disorder based on DSM-5 were
      studied in a parallel randomized controlled trial. INTERVENTION: Subjects were
      randomly assigned to receive Echium amoenum compound syrup (EACS) or citalopram
      tablet for 8 weeks. OUTCOME MEASURES: The efficacy of treatments and recurrence
      of disease were surveyed and compared according to Hamilton depression rating
      scale at weeks 0, 4, 8, 12. RESULTS: Patients in both groups of citalopram and
      EACS showed remarkable reduction in scores of Hamilton questionnaire. At the
      eighth week of treatment the mean scores in EACS group was significantly lower
      than citalopram group (p-value = 0.03). 52% of patients suffered from various
      complications in citalopram group while just 12% of patients in EACS group
      reported few complications. CONCLUSION: Clinical efficacy of this herbal drug was
      significantly higher than citalopram, and complications were also less and lower
      in EACS group. Further studies with larger groups and para-clinical assessments
      such as serologic tests and QEEG would improve our understanding of the impacts
      and mechanisms of EACS.

PMID- 29468979
TI  - Potentiation of Warfarin Associated with Salsalate Therapy Resulting in Bleeding.
AB  - BACKGROUND: Salsalate may offer many advantages over other non-steroidal
      antiinflammatory agents in patients taking warfarin, however a drug-drug
      interaction may occur which has not been reported in the medical literature or by
      the manufacturer of salsalate. OBJECTIVE: To report a case of warfarin
      potentiation associated with salsalate treatment, which resulted in bleeding.
      METHOD: Clinical review of the course of a patient, who was stable on warfarin
      when salsalate therapy was added for chronic pain. CASE REPORT: A patient taking
      stable doses of warfarin for over 1 year (with good control) was prescribed
      salsalate 3 g/day for pain in his knee and lower back. Approximately 1 month
      later he presents to the anticoagulation clinic with bruising and an
      International Normalized Ratio (INR) of 6.8. The patient had a good response to
      his salsalate therapy and wanted to continue it. The warfarin was held for 3 days
      and dose lowered by 50 %. His bruising then subsided and he had good control of
      his warfarin therapy with INRs ranging from 1.9 to 2.2 over the next 4 months.
      The patient was then lost to follow up. CONCLUSION: This case illustrates a
      strong association between starting salsalate and subsequent potentiation of
      warfarin, which heretofore has not been reported in the medical literature.

PMID- 29468980
TI  - Updates on GMSCs Treatment for Autoimmune Diseases.
AB  - BACKGROUND: Autoimmune disease is a refractory disease. Accumulating Evidence has
      revealed that the manipulation of mesenchymal stem cells may have the potential
      to control or even treat autoimmune diseases. Human gingiva-derived mesenchymal
      stem cells (GMSCs) are emerging as a new line of mesenchymal stem cells that have
      displayed some potential advantages in controlling and treating autoimmune
      diseases. OBJECTIVE: In this review, we briefly update the current understanding
      on the biology of GMSCs and their effects on preventing and treating autoimmune
      diseases. CONCLUSION: The availability of gingival mesenchymal stem cells
      (GMSCs), together with their potent capacity of multi-directional differentiation
      and inflammatory modulation, making GMSCs an ideal subtype of MSCs in treating
      autoimmune disease. Our and other studies have launched the earliest appraisal on
      GMSCs and carried out a lot of biological researches. The clinical trial of GMSCs
      on patients with autoimmune diseases will further approve their therapeutic
      effects, as well as its cellular and molecular mechanisms.

PMID- 29468981
TI  - Lenvatinib in the Therapy of Aggressive Thyroid Cancer: State of the Art and New
      Perspectives with Patents Recently Applied.
AB  - BACKGROUND AND OBJECTIVE: Lenvatinib is an oral, multitargeted Tyrosine Kinase
      Inhibitor (TKI) of Vascular Endothelial Growth Factor Receptors (VEGFR1-VEGFR3),
      fibroblast growth factor receptors (FGFR1-FGFR4), Platelet-Derived Growth Factor
      Receptor (PDGFR)alpha, rearranged during transfection (RET), and v-kit (KIT)
      signaling networks implicated in tumor angiogenesis. METHOD: Here, we review the
      scientific literature about lenvatinib in the treatment of thyroid cancer.
      RESULTS: In vitro studies have shown antineoplastic activity of lenvatinib in
      Differentiated Thyroid Cancer (DTC), mainly because of its antiangiogenetic
      effects, but a slight effect on thyroid cancer cell proliferation has been shown.
      In vivo Phase II, and Phase III studies in patients with aggressive DTC not
      responsive to radioiodine, have shown that lenvatinib administration was
      associated with an amelioration in Progression-Free Survival (PFS) with respect
      to placebo (median PFS 18.2 vs. 3.6 months). However, overall survival was not
      significantly changed. Lenvatinib is also effective in patients resistant to
      sorafenib as salvage therapy. Adverse effects of any grade occur in more than 40%
      of lenvatinib-treated patients, mainly hypertension, diarrhea, asthenia or
      fatigue, nausea, decreased appetite, and decreased weight. Discontinuations of
      the therapy because of adverse effects occur in about 14% of patients. Moreover,
      deaths considered to be drug-related can occur. CONCLUSION: On the basis of the
      above-mentioned considerations, it is necessary to prove the effectiveness of
      lenvatinib in the context of associated moderate to severe toxicities requiring
      frequent dose reduction and delays, and for this reason, many interesting patents
      have been recently applied.

PMID- 29468982
TI  - Novel Patents Targeting Interleukin-17A; Implications in Cancer and Inflammation.
AB  - BACKGROUND: IL-17A is a founding member of the IL-17 family that has been
      implicated in the pathogenesis of inflammatory-associated diseases such as cancer
      and autoimmune disease. In cancer, IL-17A participates in many key events for
      tumor development, in part by affecting innate and adaptive immune system and
      also by direct modulation of many pro-tumor events. Moreover, IL-17A
      dysregulation at the site of inflammation is associated with rheumatoid
      arthritis, multiple sclerosis, psoriasis, among others. IL-17A has emerged as a
      topic of interest and is under profound investigation for its involvement in
      several types of inflammatory-associated diseases. OBJECTIVE: This review aims to
      present an overview of the state of the art of IL-17A role in cancer and
      inflammation, as well as to describe recent patents targeting IL-17A with
      relevant clinical and biological properties for the prevention and treatment of
      cancer and inflammatory diseases. METHODS: Relevant information was obtained by
      searching in PubMed using IL-17A or IL-17, cancer and inflammation as keywords,
      while relevant patents were obtained mainly from Google Patents. RESULTS:
      Literature data indicated IL-17A as important biomolecule in the physiopathology
      of cancer and inflammatory diseases. Whereas, novel patents (2010 to 2017)
      targeting IL-17A are focused mainly on describing strategies to modulate IL-17A
      per se, co-modulation by bispecific antibodies to blocking IL-17A and important
      cytokines for IL-17A functions, upstream mechanisms and compounds to regulate IL
      17A expression. CONCLUSION: The promising effects of patented agents against IL
      17A may open new opportunities to therapeutic intervention targeting at different
      levels of involvement in the pathogenesis of cancer and inflammatory diseases.

PMID- 29468983
TI  - Synthesis and DFT Study on Hantzsch Reaction to Produce Asymmetrical Compounds of
      1,4-Dihydropyridine Derivatives for P-Glycoprotein Inhibition as Anticancer
      Agent.
AB  - BACKGROUND: P-glycoprotein (P-gp) causes the efflux of cancer chemotherapy drugs
      from tumor cells, so its inhibition can be one target for designing and synthesis
      of new anticancer drugs. OBJECTIVE: In this study, new compounds of 1,4
      dihydropyridine (DHP) were recommended as inhibitors of P-gp. METHODS: We
      synthesized new symmetrical DHP with 36% - 43% yield by the reaction of new
      reactants. In biological studies, these compounds have high lipophilicity, and
      thus low water solubility. Four reactants I with different reactivity was
      computed and compared using DFT study. The LUMO-map was differently distributed
      on each reactant. Amine intermediate underwent tautomerism as a transition state
      and it seems to play important role in reaction progress. Calculations were
      performed to select suitable reactants. RESULTS: Two different reactants I,
      including one polar group and a non-polar group, were used to produce asymmetric
      compounds with 49% - 60% yield. These asymmetric DHPs were more soluble than
      symmetric DHPs. In the final step, another selected symmetric product (by the
      elimination of chlorine atom) was synthesized in high yield (74%) by using DFT
      study. CONCLUSION: In this study, selected reactants by DFT calculation have
      increased the yield of reaction from 36% to 74% without any catalyst. The
      diversity of products is a noticeable topic. Racemic asymmetric compounds with R
      and S enantiomers have the potential for enantiomeric separation. Each of these
      enantiomers could have a different physiological effect.

PMID- 29468984
TI  - VaD - An Integrated Framework for Cognitive Rehabilitation.
AB  - BACKGROUND & OBJECTIVE: Vascular dementia is the second most common cause of
      dementia, with clinical features that depend on neural substrates affected by the
      vascular lesions. Like most neurological disorders, it involves alterations that
      range from the molecular level to neuronal networks. Such alterations begin as
      compensatory mechanisms that reshape every subsystem involved in the brain's
      homeostasis. Although there have been recent huge advances in understanding the
      pathophysiology of cognitive dysfunction, a suitable therapeutic approach to
      vascular dementia remains elusive. Pharmacological interventions have failed to
      sustainably improve cognitive function, and it is a well-known fact that there is
      a need to change the current view for providing neuroprotection and enhancing
      neurorecovery after stroke. Studies regarding cognitive training are also faced
      with the difficulty of drawing up protocols that can embrace a holistic approach
      in cognitively impaired patients. CONCLUSION: This review will present a brief
      synthesis of current results from basic research data and clinical studies
      regarding pharmacological and non-pharmacological interventions in vascular
      dementia and will offer an integrated view from the perspective of systems
      biology.

PMID- 29468985
TI  - The Role of Neurohypophyseal Hormones Vasopressin and Oxytocin in
      Neuropsychiatric Disorders.
AB  - BACKGROUND AND OBJECTIVE: Although the neurohypophyseal hormones vasopressin (VP)
      and oxytocin (OT) are mostly known for their role respectively in antidiuresis,
      and in labour, lactation and maternal behavior, both might exert widespread
      influences either on emotion and cognition in healthy subjects, showing some
      gender-related differences. They interact with each other facilitating shifts
      between positive socially- oriented and defensive states. In fact, VP amplifies
      the reactivity to stressors showing also beneficial effects on attention, verbal
      learning as well as memory, whereas OT reduces the amplitude of the stress
      response, improves emotion processing, and can play a negative effect on memory
      and verbal learning in healthy individuals. Several data indicate the possible
      involvement of these neuropeptides in the pathophysiology of psychiatric
      conditions involving social interactions, such as autism, as well as in
      schizophrenia and depression. The aim of this paper is to review the literature
      relating to the role played by neurohypophyseal hormones in neuropsychiatric
      disorders. METHODS: We analyzed the best of published literature dealing with the
      relationships between neurohypophyseal hormones and neuropsychiatric conditions
      like autism (AD), major depressive disorder (MDD), bipolar disorder (BD) and
      schozophrenia, identifying keywords and MeSH terms in Pubmed and then searching
      them. The last search was performed on December 2017. RESULTS: Several studies
      indicate a role played by OT and VP in AD, schizophrenia, MDD and BD. Even if
      conflicting data have been reported, several mechanisms may be involved in these
      behavioral diseases, such as differences in aminoacid sequence and peptide
      biological activity, neurotransmission and genetic disorders involving OT and VP
      receptors. CONCLUSION: The involvment of VP and OT in neurpopsychiatric disorders
      can support a possible beneficial therapy with OT or with VP antagonists. The
      target may be obtained using effective drug delivery methods as well as the
      association with other drugs.

PMID- 29468986
TI  - Increased Endothelial Dysfunction and Insulin Resistance in Patients with
      Klinefelter Syndrome.
AB  - BACKGROUND AND OBJECTIVE: Patients with Klinefelter Syndrome (KS) have increased
      cardiometabolic risk however the pathogenesis is not clear. We investigated the
      presence of endothelial dysfunction, insulin resistance and inflammation in an
      unconfounded population of KS. METHODS: A total of 32 patients with KS (mean age
      21.59 +/- 1.66 years) and 33 healthy control subjects (mean age: 22.15 +/- 1.03
      years) were enrolled. The demographic parameters, Asymmetric dimethylarginine
      (ADMA), homeostatic model assessment of insulin resistance (HOMA-IR) index and
      highsensitivity C-reactive protein (hs-CRP) levels were measured. RESULTS: The
      patients had higher Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH),
      insulin, HOMA-IR and ADMA levels (p < 0.001 for all) and lower High Density
      Lipoprotein Cholesterol (HDL-C) and total testosterone levels (p=0.002 and
      p<0.001, respectively), compared to the healthy controls. Total testosterone
      levels were significantly negatively correlated to ADMA (r = - 0.479, p < 0,001),
      hs-CRP (r = -0.291, p = 0.034) and positively correlated to HDL-C (r = 0.429, p =
      0.001) levels. The multivariate analysis has shown that total testosterone (beta
      = -0.412, p = 0.001) and TG (beta = 0.332, p = 0.009) levels were the significant
      independent determinants of the plasma ADMA levels. CONCLUSION: The results of
      the present study show that endothelial dysfunction and insulin resistance are
      prevalent even in the very young subjects with KS, who have no metabolic or
      cardiac problems at present. Also, hypogonadism seems to play an important role
      for increased cardiometabolic risk in patients with KS.

PMID- 29468987
TI  - Antithyroid Drugs Inactivate TSH Binding to the TSH Receptor by their Reducing
      Action.
AB  - : Backgroud and Objective: Antithyroid drugs (ATDs) [methylmercaptoimidazole
      (MMI) and propylthiouracil (PTU) ] are used to treat hyperthyroidism in Graves'
      disease. The effect of ATDs and reducing agents (mercaptoethanol, dithiothreitol
      and cysteine) on bovine (b) TSH binding to human (h) and porcine (p) TSH receptor
      (R) was examined. METHODS AND RESULTS: (1) ATDs was pre-incubated with hTSHR
      coated tube for 1- 4 h, washed free of ATDs, and then 125I-bTSH binding to hTSHR
      after 1 h incubation was examined. MMI (10-40 mM) decreased 125I-bTSH binding in
      a dose-dependent manner and binding decreased proportionally as preincubation
      time increased from 1 to 4 h. PTU (10mM) slightly decreased binding, When
      reducing agents were pre-incubated with hTSHR for 2 h, 125I-bTSH binding
      similarly decreased. (2) Porcine thyroid membrane was pre-incubated with both
      agents for 2 h. Then, the washed or unwashed membrane was incubated with 125I
      bTSH for 1 h. 125I-bTSH binding in both methods decreased. (3) When the effect of
      ATDs or reducing agents on the biological activity of 125I-bTSH and thyroid
      stimulating antibody (TSAb) was examined after gel-filtration of 125I-bTSH- and
      TSAb- treated with both reagents for 1 h, no inactivation was observed. (4) ATDs
      showed similar reducing action as reducing agents because iodine (I+) was reduced
      to I- by ATDs. CONCLUSION: ATDs inactivate the TSH-binding site of TSHR by
      reduction, although ATDs do not inactivate bTSH and TSAb activity. This suggests
      that TSAb would not stimulate the thyroid due to the inactivation of the TSHR
      when ATDs are administered to patients with Graves' disease.

PMID- 29468988
TI  - COX-2 in Radiotherapy: A Potential Target for Radioprotection and
      Radiosensitization.
AB  - BACKGROUND: Each year, millions of people die from cancer. Radiotherapy is one of
      the main treatment strategies for cancer patients. Despite the beneficial roles
      of treatment with radiation, several side effects may threaten normal tissues of
      patients in the years after treatment. DISCUSSION: Moreover, high incidences of
      second primary cancers may reduce therapeutic ratio of radiotherapy. The search
      for appropriate targets of radiosensitization of tumor cells as well as
      radioprotection of normal tissues is one of the most interesting aims in
      radiobiology. Cyclooxygenase-2 (COX-2), as an inflammatory mediator has attracted
      interests for both aims. COX-2 activity is associated with ROS production and
      inflammatory signs in normal tissues. These effects further amplify radiation
      toxicity in irradiated cells as well as adjacent cells through a phenomenon known
      as Bystander effect. Increased COX-2 expression in distant non-irradiated tissues
      causes oxidative DNA damage and elevated cancer risk. Moreover, in tumors, the
      activation of this enzyme can increase resistance of malignant cells to
      radiotherapy. Hence, the inhibition of COX-2 has been proposed for better
      therapeutic response and amelioration of normal tissues. Celecoxib is one of the
      most studied COX-2 inhibitor for radiosensitization and radioprotection, while
      some other inhibitors have shown interesting results. CONCLUSION: In this review,
      we describe the role of COX-2 in radiation normal tissue injury as well as
      irradiated bystander and non-targeted cells. In addition, mechanisms of COX-2
      induced tumor resistance to radiotherapy and the potential role of COX-2
      inhibition are discussed.

PMID- 29468989
TI  - Bovine spongiform encephalopathy (BSE) associated polymorphisms of the prion-like
      protein gene (PRND) in Korean dairy cattle and Hanwoo.

PMID- 29468990
TI  - Separation of bovine kappa-casein glycomacropeptide from sweet whey protein
      products with undetectable level of phenylalanine by protein precipitation
      followed by anion exchange chromatography.

PMID- 29468991
TI  - Characterisation of Staphylococcus aureus strains isolated from mastitis bovine
      milk in Argentina.

PMID- 29468992
TI  - Influence of postoperative pain and use of NSAID on heart rate variability of
      dairy cows.

PMID- 29468993
TI  - Prediction of sheep milk chemical composition using milk yield, pH, electrical
      conductivity and refractive index.

PMID- 29468994
TI  - Effects of dietary supplementation of pioglitazone or walnut meal on metabolic
      profiles and oxidative status in dairy cows with high pre-calving BCS.

PMID- 29468995
TI  - Aroma profile of a traditionally fermented butter (smen).

PMID- 29468996
TI  - Culture supernatant produced by Lactobacillus kefiri from kefir inhibits the
      growth of Cronobacter sakazakii.

PMID- 29468997
TI  - Investigation on the effectiveness of mid-infrared spectroscopy to predict
      detailed mineral composition of bulk milk.

PMID- 29468998
TI  - Effect of heat-induced kappa-casein dissociation on acid coagulation of milk.

PMID- 29468999
TI  - Effect of heat stress on the interaction of Streptococcus uberis with bovine
      mammary epithelial cells.

PMID- 29469000
TI  - Use of contrast-enhanced ultrasonographic examination to evaluate health status
      of mammary glands of ewes at the end of a lactation period.

PMID- 29469001
TI  - Changes of macrominerals and calcitropic hormones in serum of periparturient
      dairy cows subject to subclinical hypocalcaemia.

PMID- 29469002
TI  - Effects of chronic mastitis and its treatment with ketoprofen on the milk
      ejection curve.

PMID- 29469003
TI  - Risk factors of teat-end hyperkeratosis and its association with udder health in
      dairy ewes.

PMID- 29469005
TI  - Editorial: Going global.

PMID- 29469004
TI  - Reticulorumen temperature and pH as indicators of the likelihood of reproductive
      success.

PMID- 29469006
TI  - Welcome to new ideas and farewell to old friends.

PMID- 29469007
TI  - Erratum.

PMID- 29469008
TI  - Erratum.

PMID- 29469009
TI  - Dairy consumption and inflammatory profile: A cross-sectional population-based
      study, Sao Paulo, Brazil.
AB  - OBJECTIVES: The aim of this study was to investigate the association between
      dairy product consumption and plasma inflammatory biomarkers levels among a
      representative sample of Brazilian adults from Sao Paulo City. METHODS: Data were
      acquired from the Health Survey for Sao Paulo, a cross-sectional population-based
      study. All individuals 20 to 59 y of age with complete food consumption
      information (24-h dietary recall and food frequency questionnaire) and blood
      sample analysis were included (N = 259). The sample was separated into two groups
      according to systemic inflammatory pattern considering plasma levels of C
      reactive protein; tumor necrosis factor-alpha; soluble intracellular adhesion
      molecule; soluble vascular cell adhesion molecule, monocyte chemoattractant
      protein; interleukin-1beta, -6, -8, -10, and -12; adiponectin; leptin; and
      homocysteine. Multiple logistic regression tests were conducted to estimate the
      odds ratio for the inflammatory cluster across tertiles of dairy consumption.
      RESULTS: When adjusted by age, smoking status, and energy intake the odds ratio
      for the inflammatory cluster group in the highest tertile of yogurt consumption
      was 0.34 (95% confidence interval [CI], 0.14-0.81) relative to the reference
      tertile, demonstrating also a linear effect (Ptrend = 0.015). Cheese consumption
      exhibited an odds ratio of 2.49 (95% CI, 1.09-5.75) relative to the reference.
      CONCLUSIONS: Increasing yogurt consumption might have a protective effect on
      inflammation, whereas cheese consumption appears to be associated with a
      proinflammatory status. The results of the present study aggregate a new
      perspective on existing evidence demonstrating the importance of assessing the
      contribution of dairy products on diet and their effect on the development of non
      communicable diseases and associated risk factors.

PMID- 29469010
TI  - Effect of blood thiamine concentrations on mortality: Influence of nutritional
      status.
AB  - OBJECTIVE: To test the hypothesis that low blood thiamine concentrations in
      malnourished critically ill children are associated with higher risk of 30-d
      mortality. METHODS: Prospective cohort study in 202 consecutively admitted
      children who had whole blood thiamine concentrations assessed on admission and on
      days 5 and 10 of intensive care unit (ICU) stay. The primary outcome variable was
      30-d mortality. Mean blood thiamine concentrations within the first 10 d of ICU
      stay, age, sex, malnutrition, C-reactive protein concentration, Pediatric Index
      of Mortality 2 score, and severe sepsis/septic shock were the main potential
      exposure variables for outcome. RESULTS: Thiamine deficiency was detected in 61
      patients within the first 10 d of ICU stay, 57 cases being diagnosed on admission
      and 4 new cases on the 5th d. C-reactive protein concentration during ICU stay
      was independently associated with decreased blood thiamine concentrations (P =
      0.003). There was a significant statistical interaction between mean blood
      thiamine concentrations and malnutrition on the risk of 30-d mortality (P =
      0.002). In an adjusted analysis, mean blood thiamine concentrations were
      associated with a decrease in the mortality risk in malnourished patients (odds
      ratio = 0.85; 95% confidence interval [CI]: 0.73-0.98; P = 0.029), whereas no
      effect was noted for well-nourished patients (odds ratio: 1.03; 95% CI: 0.94
      1.13; P = 0.46). CONCLUSIONS: Blood thiamine concentration probably has a
      protective effect on the risk of 30-d mortality in malnourished patients but not
      in those who were well nourished.

PMID- 29469011
TI  - The effects of resistance training of swallowing muscles on dysphagia in older
      people: A cluster, randomized, controlled trial.
AB  - OBJECTIVE: This study examined the effects of resistance training of swallowing
      muscles in community-dwelling older individuals with dysphagia. METHODS: A
      cluster randomized controlled trial was performed in day-service and day-care
      facilities. The participants were older (>=65 y) community-dwelling individuals
      with dysphagia. The intervention group performed a tongue resistance exercise and
      a head flexion exercise against manual resistance. Both groups received a
      brochure on dysphagia rehabilitation. The primary endpoint was an improvement in
      dysphagia assessed by the Eating Assessment Tool (EAT-10) score. Tongue pressure
      was the secondary endpoint. RESULTS: Participants included 47 men and 57 women,
      with a mean age +/- standard deviation of 80 +/- 7 y. At baseline, the median EAT
      10 score was 7 (interquartile range, 5-12). A total of 91 patients, 43 in the
      intervention group (8 clusters) versus 48 in the control group (11 clusters),
      were assessed postintervention. The percentage of participants with EAT-10 scores
      <3 was not statistically significantly different between the two groups
      (intervention group, 23% versus control group, 19%, P = 0.598). Postintervention
      median EAT-10 scores were 6 (interquartile range, 3-10) in each group (P = 0.665)
      and mean tongue pressure was 23.9 +/- 10.0 versus 25.9 +/- 10.9 kPa (P = 0.376).
      The intervention did not significantly affect the EAT-10 score or tongue pressure
      in a mixed effects random intercept model. The Mini Nutritional Assessment Short
      Form score correlated significantly with the postintervention EAT-10 score.
      CONCLUSIONS: Resistance training of swallowing muscles did not improve dysphagia
      in this study. Better nutritional status correlated independently with improved
      swallowing function.

PMID- 29469012
TI  - Nutritional status and postoperative outcomes in patients with gastrointestinal
      cancer in Vietnam: a retrospective cohort study.
AB  - BACKGROUND: Nutritional support for surgical care is crucial because hospital
      malnutrition is rather common. However, low- and middle-income countries have not
      adequately addressed nutritional management of surgical patients. To highlight
      need for nutritional management in surgical patients, the present study aimed to
      describe preoperative nutritional status in patients who underwent
      gastrointestinal cancer surgery in Vietnam and to investigate the relationship
      between preoperative malnutrition and adverse outcomes, such as postoperative
      complications and prolonged length of hospital stay. METHODS: We reviewed medical
      records of patients who underwent a major curative surgery for gastrointestinal
      cancer at the national hospital in Ho Chi Minh City, Vietnam. We identified
      preoperative malnutrition based on body mass index and serum albumin level, and
      postoperative complications in the first 30 d postoperative. We estimated the
      relative influence of malnutrition on complications and length of hospital stay
      using multivariate regression models. RESULTS: Of 459 eligible patients, 63% had
      colorectal cancer, 33% gastric cancer, and 4% esophageal cancer. The prevalence
      of malnutrition was 19%. No patients died during hospitalization; however, 26%
      developed complications after surgery. The average length of hospital stay was 14
      d. After controlling for potential confounders, preoperative malnutrition was
      associated with an increased risk of postoperative complications (odds ratio =
      1.97) and prolonged hospital stay (2.8 d). CONCLUSIONS: Preoperative malnutrition
      affects surgical outcomes among patients with gastrointestinal cancer in Vietnam.
      We recommend implementing preoperative nutritional interventions to achieve
      better outcomes among surgical cancer patients.

PMID- 29469013
TI  - Intermittent food restriction in female rats induces SREBP high expression in
      hypothalamus and immediately postfasting hyperphagia.
AB  - OBJECTIVE: We investigated the effect of intermittent food restriction (IFR)
      cycles on hypothalamic expression of lipogenic proteins and induction of
      overeating. METHODS: Female Wistar rats were distributed in three groups: free
      access to feed (control, C), 2 d feed restriction at 50% of C intake followed by
      3 d (restricted 3, R3) or 5 d (restricted 5, R5) ad libitum feeding. After 6 wk,
      the rats were submitted to euthanasia and collected the hypothalamus and blood.
      The deposits of retroperitoneal, mesenteric, and gonadal fat were weighed. The
      expression of the mRNA for sterol regulatory element binding protein (SREBP) 1c
      and 2 and acetyl-CoA carboxylase in the hypothalamus were determined by real-time
      polymerase chain reaction, and glucose and triacylglycerol were evaluated by a
      commercial kit. Body mass and food intake were measured daily. RESULTS: IFR
      promoted increased expression of SREBP-2 in both treated groups and, in R5,
      increased expression of SREBP-1c. The serum triacylglycerol, mesenteric deposit,
      and total fat content were higher in R3. Neither of the treatment intervals
      altered the expression of the mRNA of acetyl-CoA carboxylase enzyme but induced
      hyperglycemia and higher food intake immediately after food restriction.
      CONCLUSION: IFR affected the expression of SREBP-1c in R5 and SREBP-2 in the
      hypothalamus and caused overeating immediately after fasting in both groups. We
      suggest that hypothalamic and peripheral alterations, coupled with compulsive
      eating behavior in the ad libitum period, indicate risks for diabetes mellitus
      and recovery of body mass after interruption of IFR.

PMID- 29469014
TI  - Effect of mineral status and glucocorticoid use on bone mineral density in
      patients with Crohn's disease.
AB  - OBJECTIVES: Crohn's disease (CD) is a condition that is characterized by chronic
      inflammation. The presence of multifactorial pathogenesis that results from
      inflammation is associated with low micronutrient consumption and glucocorticoid
      use, which may be related to bone health. This study aimed to evaluate the
      relationship between dietary mineral intake and glucocorticoid use in bone
      mineral density (BMD) in patients with CD. METHODS: A cross-sectional study of 62
      patients with CD ages 20 y to 40 y measured their macro- and micronutrient intake
      with a 3-d food record. The lumbar spine and femoral neck BMDs were determined
      using a bone densitometry technique. The C-reactive protein (CRP) levels and
      erythrocyte sedimentation rate (ESR) values were also noted. RESULTS: Dietary
      intake of calcium, zinc, and magnesium was below the reference values but the
      phosphorus intake level was within the normal value range. Patients with
      osteopenia and osteoporosis accounted for 17.7% and 14.5%, respectively, of the
      total number of participants. Significant bone loss was found in 22.6% of
      patients taking glucocorticoid medications. BMD was significantly reduced and
      also observed in patients in the active phase of their disease. Zinc and calcium
      intakes were found to be correlated with reduced femoral neck BMD. The mean CRP
      and ESR values were above the normal ranges. Significant differences in age and
      ESR were observed between patients with normal and reduced BMD (P <0.05).
      CONCLUSIONS: Low calcium and zinc intake, glucocorticoid use, and active disease
      phase are favorable conditions for bone loss in patients with Crohn's disease.

PMID- 29469015
TI  - Do celiac disease and non-celiac gluten sensitivity have the same effects on
      reproductive disorders?
AB  - OBJECTIVES: The wide spectrum of clinical symptoms of celiac disease (CD) is
      partly due to the malnourished state caused by the malabsorption of micro- and
      macronutrients. It has been suggested that fertility problems and obstetric
      complications may be a consequence of the endocrine disorders caused by selective
      nutrient deficiencies. The same selective nutrient deficiencies as in CD could be
      a reason for fertility problems in non-celiac gluten sensitivity (NCGS). The aim
      of this study was to investigate the effect of nutrient deficiencies in CD and
      NCGS on fertility problems. METHOD: A literature review of fertility problems in
      men and women and nutrient deficiencies associated with CD and NCGS, was
      performed up to May 2017. RESULTS: The same selective nutrient deficiencies
      (folate, iron, vitamin B12, and vitamin D) in CD and NCGS could be a reason for
      fertility problems. CONCLUSIONS: CD is postulated to be considered in the
      preconceptional screening of patients with reproductive disorders, but for non
      celiac gluten sensitivity, the effect on fertility is not yet proven.

PMID- 29469016
TI  - The potential health and economic effects of plant-based food patterns in Belgium
      and the United Kingdom.
AB  - OBJECTIVE: Policymakers increasingly require scientific evidence on both health
      and economic consequences of different nutritional patterns. The aim of this
      study was to assess health and economic effects of Mediterranean and soy
      containing diets. Selected countries were Belgium and the United Kingdom.
      METHODS: Cost-effectiveness of these plant-based food patterns was assessed in
      comparison with a "conventional" diet using an age- and sex-dependent prediction
      model. The model allowed the prediction of health outcomes and related health
      care costs for the food patterns over 20 y. A societal perspective was applied
      for cost calculation and health outcomes were expressed in quality-adjusted life
      years (QALYs). RESULTS: For Belgium, a soy-containing diet is estimated to lead
      to 202 QALYs and 107 QALYs per 1000 women and men, respectively, whereas societal
      savings of ?2 146 000 and ?1 653 000 are predicted. For the United Kingdom, a
      gain of 159 QALYs and 100 QALYs per 1000 women and men, respectively, is
      estimated, as are a prediction of savings of L1 580 000 and L1 606 000. For the
      Mediterranean diet in the corresponding estimates for Belgium are 184 QALYs and
      148 QALYs per 1000 women and men, respectively, and savings of ?1 618 000 and ?1
      595 000. For the United Kingdom, these are 122 QALYs and 110 QALYs per 1000 women
      and men, respectively, and savings of L1 155 000 and L1 046 000, respectively.
      CONCLUSION: A wider implementation of plant-based eating would lead to large net
      economic gains for society and improved health outcomes for the population.

PMID- 29469017
TI  - Psychopathological correlates of eating behavior among Portuguese undergraduate
      students.
AB  - OBJECTIVES: The aim of this study was to explore the relationships between eating
      behavior dimensions and psychopathological symptoms among Portuguese
      undergraduate students. METHODS: We studied 258 participants (62.4% women)
      regarding eating behavior dimensions (emotional, external and binge eating,
      flexible and rigid control of eating behavior, and eating self-efficacy),
      psychopathological distress (as assessed by the Brief Symptom Inventory), and
      body mass index. In addition to studying bivariate associations between eating
      behavior dimensions and psychopathological subscales and indexes, what we believe
      to be a novel analytical approach, considering simultaneously the effects of the
      overall level of psychopathological distress and the relevance of specific
      symptoms on the eating behavior dimensions. RESULTS: Emotional, external, and
      binge eating had positive correlations with psychopathological symptomatology,
      whereas eating self-efficacy was negatively associated. CONCLUSIONS: Multivariate
      analysis showed that the overall level of psychopathological distress (combined
      with body mass index, among women) had a larger effect on eating behavior than
      the relevance of specific symptoms.

PMID- 29469018
TI  - Evaluation of malnutrition development risk in hospitalized children.
AB  - OBJECTIVES: Many screening methods, such as the Screening Tool Risk on
      Nutritional Status and Growth (STRONGkids) and the Pediatric Yorkhill
      Malnutrition Score (PYMS), have been developed to detect malnutrition in
      pediatric patients. We aimed to explore the prevalence of malnutrition risk in
      hospitalized children via symptoms and identification of contributing factors,
      and to examine the efficacy of malnutrition screening tools for hospitalized
      children. METHODS: STRONGkids and PYMS were applied to 1513 inpatients at 37
      hospitals in 26 cities from different regions of Turkey. Physical measurements
      were collected at hospital admission and at discharge. z-Scores of height-for
      age, weight-for-age, weight-for-height, and body mass index-for-age were
      calculated. RESULTS: Overall, 1513 patients were included in the study. A body
      mass index standard deviation score of less than -2 was present in 9.5% of the
      study population at hospital admission, whereas 11.2% of the participants had a
      weight-for-length/height score of less than -2 at hospital admission. According
      to STRONGkids results, the proportion of the patients with an underlying chronic
      disease was higher for the patients at high risk of malnutrition than for the
      patients at medium or low risk (91% compared with 47% or 45%, respectively). PYMS
      results indicated that patients at high risk of malnutrition have more chronic
      diseases (75%) than the patients at medium or low risk of malnutrition (55% and
      44%, respectively). CONCLUSIONS: Use of anthropometric measurements in addition
      to screening tools to identify hospital malnutrition (such as PYMS, STRONGkids)
      will prevent some nutritional risk patients from being overlooked.

PMID- 29469019
TI  - Longitudinal adherence to a dietary pattern and risk of depressive symptoms: the
      Furukawa Nutrition and Health Study.
AB  - OBJECTIVE: We explored the association of 3-year adherence to a dietary pattern
      based on nutrients that may be related to mood with the development of depressive
      symptoms in Japanese employees. METHODS: Participants were 903 employees free
      from depressive symptoms at baseline and who attended the 3-year follow-up.
      Participants with depressive symptoms were defined as those with a score >=16 on
      the Center for Epidemiologic Studies Depression Scale. Dietary patterns were
      derived using reduced-rank regression at baseline and at the 3-year follow-up
      survey using a validated, self-administered diet history questionnaire. Based on
      changes in dietary pattern scores between baseline and follow-up surveys,
      participants were categorized into four groups: Maintained high scores, improved
      scores, decreased scores, and maintained low scores. Logistic regression was used
      to estimate odds ratios of depressive symptoms according to changes in dietary
      pattern scores. RESULTS: Maintaining high or improving adherence to a diet rich
      in vegetables, mushrooms, seaweeds, soybean products, green tea, potatoes,
      fruits, and fish and low in rice over 3 y was associated with a decreased risk of
      depressive symptoms. The multivariable-adjusted odds ratio (95% confidence
      intervals) of developing depressive symptoms for maintained high scores versus
      maintained low scores was 0.57 (0.35-0.93) and for improved scores versus
      maintained low scores was 0.54 (0.29-1.01). The association with the severe
      depressive status was more pronounced. CONCLUSION: Maintaining high or improving
      adherence to a dietary pattern derived by reduced-rank regression is associated
      with a lower risk of depression among Japanese employees.

PMID- 29469020
TI  - Changes in nutritional state and dysphagia in stroke patients monitored during a
      14-d period in a Burkina Faso hospital setting.
AB  - INTRODUCTION: Dysphagia and undernourishment are common in cerebrovascular
      accident (stroke) patients in developed countries. Despite the dietary
      transition, there is little information available in Africa on this topic. This
      study aims to assess the prevalence of undernourishment and dysphagia in stroke
      patients in two Burkina Faso teaching hospitals at a starting point (D0), on the
      eighth day, and on the 14th (D14) and to specify factors related to
      undernourishment at day 14. METHODOLOGY: The nutritional state of the patients
      was assessed using body mass index, triceps skinfold thickness, and mid-upper arm
      circumference. Dysphagia was identified using the Practical Aspiration Screening
      Schema. RESULTS: A total of 222 patients were included in the study. From D0 to
      D14, the prevalence of undernourishment increased from 25.2% to 31.0% and the
      prevalence of dysphagia decreased from 37.4% to 15.8%. All nutritional criteria
      worsened. In a multivariate analysis, undernourishment was more present at D14
      for women (odds ratio [OR] = 7.01; 95% confidence interval [CI]: 1.51-32.56, P =
      0.01) and was less present if weight (OR = 0.69; 95% CI: 0.60-0.79, P = 0.0001)
      or triceps skinfold thickness (OR = 0.85; 95% CI: 0.74-0.99, P = 0.03) were high
      at D0. CONCLUSION: The prevalence of undernourishment was high at D0 and
      increased during the monitoring period. It would be advisable to monitor
      patients' weight and triceps skinfold thickness, to optimize care for women and
      patients with low weight or triceps skinfold thickness at D0, to monitor
      dysphagia, and to inform patients, families, and relevant staff of nutritional
      concerns after a cerebrovascular accident.

PMID- 29469021
TI  - Perinatal and lifestyle factors mediate the association between maternal
      education and preschool children's weight status: the ToyBox study.
AB  - OBJECTIVE: This study aimed to explore the associations among perinatal,
      sociodemographic, and behavioral factors and preschool overweight/obesity.
      METHODS: Data were collected from 7541 European preschoolers in May/June 2012.
      Children's anthropometrics were measured, and parents self-reported all other
      data via questionnaires. Level of statistical significance was set at P <= 0.05.
      RESULTS: Certain perinatal factors (i.e., maternal prepregnancy
      overweight/obesity, maternal excess gestational weight gain, excess birth weight,
      and "rapid growth velocity"), children's energy balance-related behaviors (i.e.,
      high sugar-sweetened beverage consumption, increased screen time, reduced active
      play time), family sociodemographic characteristics (i.e., Eastern or Southern
      Europe, low maternal and paternal education), and parental overweight/obesity
      were identified as correlates of preschoolers' overweight/obesity. Furthermore,
      maternal prepregnancy overweight/obesity, children's "rapid growth velocity," and
      increased screen time mediated by 21.2%, 12.5%, and 5.7%, respectively, the
      association between maternal education and preschoolers' body mass index.
      CONCLUSION: This study highlighted positive associations of preschooler's
      overweight/obesity with excess maternal prepregnancy and gestational weight gain,
      excess birth weight and "rapid growth velocity," Southern or Eastern European
      region, and parental overweight/obesity. Moreover, maternal prepregnancy
      overweight/obesity, children's "rapid growth velocity," and increased screen time
      partially mediated the association between maternal education and preschoolers'
      body mass index. The findings of the present study may support childhood obesity
      prevention initiatives, because vulnerable population groups and most
      specifically low-educated families should be prioritized. Among other fields,
      these intervention initiatives should also focus on the importance of normal
      prepregnancy maternal weight status, normal growth velocity during infancy, and
      retaining preschool children's screen time within recommendations.

PMID- 29469022
TI  - Obesity candidate genes, gestational weight gain, and body weight changes in
      pregnant women.
AB  - OBJECTIVE: To examine the associations of two obesity-associated genes, FTO
      (rs9939609) and GNB3 (rs5443) single nucleotide polymorphisms (SNPs), with early
      pregnancy body mass index, gestational weight gain, and postpartum weight
      retention. METHODS: Secondary data analysis of self-identified white (n = 580)
      and black (n = 194) women who participated in a randomized controlled trial (2009
      2014) and provided a saliva sample of DNA. Bivariate relationships were assessed
      using analysis of variance. Multiple regression models assessed the relationship
      between outcomes and gene SNPs, controlling for income, parity, and smoking
      status. RESULTS: FTO and GNB3 gene associations with pregnancy weight were
      different by racial group and early pregnancy body mass index. Obese black women
      homozygote for the FTO risk allele (AA) had a higher gestational weight gain
      compared with non-risk homozygotes (TT) (P = 0.006). GNB3 non-risk CC homozygotes
      tended to have a lower gestational weight gain compared with heterozygotes (P =
      0.05). White GNB3 C carriers tended to be heavier in early pregnancy (P <0.1) and
      GNB3 homozygote (TT) overweight women tended to have lower postpartum weight
      retention than C carriers. CONCLUSIONS: The FTO gene and possibly the GNB3 gene
      are associated with high gestational weight gain in obese black women. Obese
      carriers of the FTO risk allele gained 4.1 kg (AT) and 7.6 kg (TT) more than
      those without risk alleles. Overweight GNB3 heterozygotes (CT) gained 6.6 kg less
      than homozygotes (CC). Overweight or obese black women who have either risk
      variant are at risk for high gestational weight gain.

PMID- 29469023
TI  - Influence of a multidisciplinary protocol on nutritional status at diagnosis in
      amyotrophic lateral sclerosis.
AB  - OBJECTIVE: The aim of this study were to understand the influence of a
      multidisciplinary care protocol in amyotrophic lateral sclerosis (ALS) on the
      change in the delay of remission to the nutrition specialist and the initial
      nutritional status. METHODS: A cohort study was performed in 43 patients with ALS
      who were referred to the Nutrition Unit between April 2015 and April 2017.
      Anthropometric parameters and diagnostic times were collected, and the
      nutritional status was studied through subjective global assessment (SGA).
      Patients who were included before (control cohort [NoP]) and after (protocol
      cohort [P]) a multidisciplinary protocol were compared. The mean age of the
      participants was 66.79 y (10.86 y). Of the patients, 62.8% belonged to the
      protocol cohort. RESULTS: Patients who started the protocol had a lower delay in
      initial assessment by a nutrition specialist (P:2 [1-6] mo/NoP:12 [10-29] mo; P =
      0.03). When the nutritional status was analyzed according to the SGA, more
      patients who did not initiate protocol were in the state of severe malnutrition
      (C) (P 22.2% versus NoP 60%; P = 0.01). Entry into the protocol was an
      independent protective factor of the presence of severe malnutrition at the
      beginning of the nutritional follow-up (odds ratio, 0.20; 95% confidence
      interval, 0.03-0.73; P = 0.02). CONCLUSIONS: The implementation of a
      multidisciplinary protocol in ALS allowed patients to present a lower percentage
      of severe malnutrition in an initial assessment by the nutrition specialist. This
      protocol is a protective factor for the presence of malnutrition at the beginning
      of support.

PMID- 29469025
TI  - Sleep duration and consumption of sugar-sweetened beverages and energy drinks
      among adolescents.
AB  - OBJECTIVE: To examine the relationship between sleep duration and consumption of
      sugar sweetened beverages (SSBs) and energy drinks (EDs) among adolescents.
      METHODS: Data on 9,473 adolescents aged 11-20 years were obtained from the 2015
      cycle of the Ontario Student Drug Use and Health Survey, a province-wide and
      cross-sectional school based survey of students in middle and high school.
      Respondents self-reported their sleep duration and consumption of SSBs and EDs.
      Those who did not meet the age-appropriate sleep duration recommendation were
      considered short sleepers. RESULTS: Overall, 81.4% and 12.0% of respondents
      reported that they had at least one SSBs and EDs in the past week, respectively.
      Males were more likely than females to consume SSBs and EDs. High school students
      were more likely than those in middle school to report drinking EDs. After
      adjusting for multiple covariates, results from logistic regression analyses
      indicated that short sleep duration was associated with greater odds of SSB
      consumption in middle school students (odd ratio (OR) = 1.64, 95% confidence
      interval (CI) = 1.18-2.11), but not those in high school (OR = 1.06, 95% CI =
      0.86-1.31). Short sleep duration was associated with greater odds of ED
      consumption in both middle (OR = 1.60, 95% CI = 1.10-2.34) and high school (OR =
      1.78, 95% CI = 1.38-2.30) students. CONCLUSION: Short sleep duration was
      associated with consumption of EDs in middle and high school students and with
      SSBs in middle school students only. Future studies are needed to establish
      causality and to determine whether improving sleep patterns can reduce the
      consumption of SSBs and EDs among adolescents.

PMID- 29469024
TI  - Association between body composition and pulmonary function in children and young
      people with cystic fibrosis.
AB  - OBJECTIVES: Body mass index (BMI) has significant limitations when assessing
      nutritional status in pediatric patients with cystic fibrosis (CF). We evaluated
      whether measurements of lean body mass (LBM) and fat mass (FM) are more sensitive
      nutritional parameters by testing their association with pulmonary function in
      adolescent patients with CF. METHODS: Sixty-nine male and female adolescents with
      CF were studied (age: 14.5 +/- 2.3, BMI: 19.5 +/- 2.3 kg/m2). Dual-energy x-ray
      absorptiometry (DXA) was used to measure total and segmental (appendicular,
      truncal) body composition (FM, LBM bone mineral density, and content) as routine
      care to monitor bone health. Correlation and multiple regression analyses were
      performed to assess the association among body composition variables and forced
      expiratory volume in 1 s (FEV1). We also evaluated the influence of the F508del
      mutation on body composition. RESULTS: FEV1 was significantly associated with
      total (r = 0.68, P <0.001), truncal (r = 0.71, P <0.001), and appendicular (r =
      0.67, P <0.001) LBM, whereas it was not associated with total (r = 0.02, P =
      0.89) and truncal (r = 0.04, P = 0.77) FM. BMI had a significant but weaker
      correlation with FEV1 (r = 0.52, P <0.001) compared with LBM. LBM was the only
      significant predictor of FEV1 in fully adjusted regression models. CONCLUSIONS:
      LBM is a significant predictor of pulmonary function in CF adolescent patients.
      DXA scanning performed as part of routine bone health monitoring in CF can
      provide important body composition data relevant to clinical interventions that
      optimize nutritional status. DXA reference data for LBM in non-adult populations
      are needed to enhance diagnostic assessment and monitor clinical progression of
      CF.

PMID- 29469026
TI  - Effect of nutritional status on mortality in patients undergoing coronary artery
      bypass grafting.
AB  - OBJECTIVES: The prognostic effects of poor nutritional status and cardiac
      cachexia on coronary artery disease (CAD) are not clearly understood. A well
      accepted nutritional status parameter, the prognostic nutritional index (PNI),
      which was first demonstrated to be valuable in patients with cancer and those
      undergoing gastrointestinal surgery, was introduced to patients requiring
      coronary artery bypass grafting (CABG). The aim of the present study was to
      evaluate the prognostic value of PNI in patients with CAD undergoing CABG.
      METHODS: We evaluated the in-hospital and long-term (3-y) prognostic effect of
      PNI on 644 patients with CAD undergoing CABG. Baseline characteristics and
      outcomes were compared among the patients by PNI and categorized accordingly: Q1,
      Q2, Q3, and Q4. RESULTS: Patients with lower PNI had significantly higher in
      hospital and long-term mortality. Patients with lower PNI levels (Q1) had higher
      in-hospital mortality and had 12 times higher mortality rates than those with
      higher PNI levels (Q4). The higher PNI group had the lower rates and was used as
      the reference. Long-term mortality was higher in patients with lower PNI (Q1)-4.9
      times higher than in the higher PNI group (Q4). In-hospital and long-term
      mortality rates were similar in the non-lower PNI groups (Q2-4). CONCLUSION: The
      present study demonstrated that PNI, calculated based on serum albumin level and
      lymphocyte count, is an independent prognostic factor for mortality in patients
      undergoing CABG.

PMID- 29469028
TI  - Effects of short-term dietary restriction and glutamine supplementation in vitro
      on the modulation of inflammatory properties.
AB  - OBJECTIVE: Dietary restriction (DR) is a nutritional intervention that exerts
      profound effects on biochemical and immunologic parameters, modulating some
      inflammatory properties. Glutamine (GLN) is a conditionally essential amino acid
      that can modulate inflammatory properties. However, there is a lack of data
      evaluating the effects of DR and GLN supplementation, especially in relation to
      inflammatory cytokine production and the expression of transcription factors such
      as nuclear factor (NF)-kappaB. METHODS: We subjected 3-mo-old male Balb/c mice to
      DR by reducing their food intake by 30%. DR animals lost weight and showed
      reduced levels of serum triacylglycerols, glucose, cholesterol, and calcium as
      well as a reduction in bone density. Additionally, blood, peritoneal, and spleen
      cellularity were reduced, lowering the number of peritoneal F4/80- and CD86
      positive cells and the total number of splenic CD4- and CD8-positive cells.
      RESULTS: The production of interleukin (IL)-10 and the expression of NF-kappaB in
      splenic cells were not affected by DR or by GLN supplementation. However,
      peritoneal macrophages from DR animals showed reduced IL-12 and tumor necrosis
      factor-alpha production and increased IL-10 production with reduced
      phosphorylation of NF-kappaB expression. Additionally, GLN was able to modulate
      cytokine production by peritoneal cells from the control group, although no
      effects were observed in cells from the DR group. CONCLUSION: DR induces
      biochemical and immunologic changes, in particular by reducing IL-12 and tumor
      necrosis factor-alpha production by macrophages and clearly upregulating IL-10
      production, whereas GLN supplementation did not modify these parameters in cells
      from DR animals.

PMID- 29469027
TI  - Reduced mortality risk by a polyphenol-rich diet: An analysis from the Moli-sani
      study.
AB  - OBJECTIVES: The effect of the polyphenol content of the human diet on mortality
      risk is not yet fully understood. The aim of this study was to evaluate the
      association of a polyphenol-rich diet with mortality rate and a possible
      mediation effect by inflammation, in what we believe to be a novel, holistic
      approach. METHODS: We analyzed 21 302 participants (10 980 women and 10 322 men,
      aged >=35 y) from the Moli-sani cohort. The participants were followed up for a
      median of 8.3 y. The European Prospective Investigation into Cancer and Nutrition
      food frequency questionnaire (FFQ) was used for dietary assessment. Flavonol,
      flavone, flavanone, flavanol, anthocyanin, isoflavone, and lignan intakes were
      calculated using European Food Information Resource-Bioactive Substances in Food
      Information Systems and the polyphenol antioxidant content (PAC)-score was
      constructed to assess the total content of these nutrients in the diet. RESULTS:
      Participants included in the highest quintile of intake of various polyphenol
      classes and subclasses presented a significant lower all-cause mortality risk
      compared with those in the lowest group of consumption (hazard ratio [HR] < 1; P
      <0.05). Cox regression analyses adjusted for potential confounders indicated that
      participants in higher quintiles of PAC-score had lower all-cause mortality risk
      (HR <1; P <0.05). When cause-specific mortality rates were considered, similar
      effects were observed for cardiocerebrovascular and cancer mortality (HR <1; P
      <0.05). CONCLUSIONS: The polyphenol content of the diet was associated with
      reduced mortality risk in a Mediterranean population, possibly through an
      antiinflammatory mechanism.

PMID- 29469029
TI  - Preclinical evaluation of degradation kinetics and elemental mapping of first-
      and second-generation bioresorbable magnesium scaffolds.
AB  - AIMS: Because vascular restoration therapy using bioresorbable vascular scaffolds
      (BRS) remains an appealing concept to restore vasoreactivity, an understanding of
      biodegradation remains paramount during preclinical testing. We therefore aimed
      to investigate the qualitative and temporal course of degradation of magnesium
      alloy-based bioresorbable vascular scaffolds in juvenile swine. METHODS AND
      RESULTS: Qualitative characterisation of biodegradation was performed in 41
      DREAMS 1G up to three years, while degradation kinetics were acquired in 54
      DREAMS 2G implanted into porcine coronary arteries for 28, 90 and 180 days, one
      and two years. Assessment of end product composition was achieved in DREAMS 2G at
      180 days. Myocardium was examined, while an OCT attenuation score was derived at
      strut level from 180 days to two years in DREAMS 2G. Degradation of DREAMS
      entails two corrosive phases. At one year, 94.8% of the magnesium was bioabsorbed
      in DREAMS 2G and, at two years, magnesium was completely replaced by amorphous
      calcium phosphate. Von Kossa staining revealed variable peri-strut mineralisation
      at all time points and only small focal myocardial emboli observed in one animal
      in the 180 days cohort. Strut discontinuity density was low at 28 days (0.5+/
      0.57 per mm) and increased to a density above 7.5 per mm up to one year. OCT
      attenuation score correlated well with strut-based degradation analysis up to two
      years. CONCLUSIONS: While the current set of data supports vascular safety,
      clinical trials are warranted to prove the concept of vascular restoration
      following DREAMS implantation.

PMID- 29469030
TI  - The efficacy of early versus delayed P2Y12 inhibition in percutaneous coronary
      intervention for ST-elevation myocardial infarction: a systematic review and meta
      analysis.
AB  - AIMS: The aim of this meta-analysis was to compare the benefit of "early" vs.
      "delayed" P2Y12 inhibition in patients undergoing percutaneous coronary
      intervention (PCI) for ST-elevation myocardial infarction (STEMI). METHODS AND
      RESULTS: We conducted a meta-analysis including seven randomised controlled
      trials (RCTs) which compared early vs. delayed P2Y12inhibition in STEMI patients
      scheduled for PCI, providing data on major adverse cardiac events (MACE), all
      cause death, and major bleeding. The primary endpoint was MACE. Secondary
      endpoints included stent thrombosis and the use of GP IIb/IIIa inhibitors (GPI).
      All endpoints were analysed at the shortest follow-up available. A total of 9,648
      patients were included ("early"=4,792, "delayed"=4,856). "Early" P2Y12 inhibition
      was associated with a significant reduction in MACE rate (OR 0.73, 95% CI: 0.61
      0.88, p=0.0008), myocardial infarction (OR 0.71, 95% CI: 0.57-0.90, p=0.004),
      bail-out GPI use (OR 0.87, 95% CI: 0.75-1.00, p=0.04) and improved coronary
      reperfusion before PCI (OR for Thrombolysis In Myocardial Infarction [TIMI] flow
      grade 2-3=1.12, 95% CI: 1.00-1.26, p=0.04). Major bleeding was not increased (OR
      0.87, 95% CI: 0.62-1.21, p=0.41). CONCLUSIONS: A strategy of early effective
      P2Y12 inhibition in PCI of STEMI appears to improve coronary reperfusion before
      PCI, and reduce MACE, MI and bail-out GPI use without increase of major bleeding.

PMID- 29469031
TI  - Ad hoc percutaneous paravalvular leak closure after transcatheter aortic valve
      replacement facilitated by integrated multimodality imaging.

PMID- 29469032
TI  - Pregnancy in papillary thyroid cancer survivors
AB  - OBJECTIVE: To evaluate "papillary thyroid carcinoma-pregnancy" interaction among
      cancer survivors. MATERIAL AND METHODS: The clinical records of 8 pregnant women
      who received treatment for papillary thyroid cancer before their pregnancy were
      evaluated. Clinical features, pregnancy/perinatal outcomes and high-risk factors
      were compared with 45 controls who were randomly assigned from the institutional
      perinatal medicine database. RESULTS: Patients in the cancer group were older
      than the control group (34.3 vs 29.8 years). The cesarean section rate was higher
      (62.5% vs 33.3%) and the APGAR scores at the 1st and 5th minutes were lower in
      the cancer group. CONCLUSION: Management of pregnancies with papillary thyroid
      cancer treatment and follow-up requires a multidisciplinary approach with careful
      antenatal care and perinatal surveillance. Patients who have received papillary
      thyroid cancer treatment can safely undergo pregnancy.

PMID- 29469034
TI  - Early Successes in an Open Access, Provincially Funded Hepatitis C Treatment
      Program in Prince Edward Island.
AB  - INTRODUCTION: The availability of curative hepatitis C therapies has created an
      opportunity to improve treatment delivery and access. Local providers,
      government, industry, and community groups in Prince Edward Island developed an
      innovative province-wide care model. Our goal was to describe the first year of
      program implementation. MATERIAL AND METHODS: Using a communitybased prospective
      observational study design, all chronic hepatitis C referrals received from April
      2015 to April 2016 were recorded in a database. Primary analysis assessed the
      time from referral to assessment/treatment, as well as the number of referrals,
      assessments, and treatment initiations. Secondary objectives included: (1)
      treatment effectiveness using intention-to-treat analysis; and (2) patient
      treatment experience assessed using demographics, adverse events, and medication
      adherence. RESULTS: During the study period 242 referrals were received, 123
      patients were seen for intake assessments, and 93 initiated direct-acting
      antiviral therapy based on medical need. This is compared to 4 treatment
      initiations in the previous 2 years. The median time from assessment to treatment
      initiation was 3 weeks. Eighty-two of 84 (97.6%, 95% CI 91.7 - 99.7%) patients
      for whom outcome data were available achieved sustained virologic response at 12
      weeks post-treatment; 1 was lost to follow-up and 1 died from an unrelated event.
      In the voluntary registry, 39.7% of patients reported missed treatment doses.
      CONCLUSION: In conclusion, results from the first 12 months of this multi-phase
      hepatitis C elimination strategy demonstrate improved access to treatment, and
      high rates of safe engagement and cure for patients living with chronic hepatitis
      C genotype 1 infections.

PMID- 29469035
TI  - Antifibrotic Mechanism of Pinocembrin: Impact on Oxidative Stress, Inflammation
      and TGF-beta /Smad Inhibition in Rats.
AB  - INTRODUCTION: The present study aimed to elucidate the potential antifibrotic
      effects of pinocembrin (PIN), a flavanone found abundantly in honey and propolis,
      by studying its effect on different oxidative stress, inflammatory and fibrosis
      markers in an experimental model of CCl4-induced liver fibrosis. MATERIAL AND
      METHODS: PIN (20 mg/kg) was given orally 3 times/week for 6 consecutive weeks
      alternating with CCl4 (0.5 mL/kg, 1:1 mixture with corn oil, i. p.) twice weekly.
      Different hepatotoxicity indices, oxidative stress, inflammatory and liver
      fibrosis markers were assessed. RESULTS: PIN significantly restored liver
      transaminases and total cholesterol to normal levels. Also, PIN ameliorated
      oxidative stress injury evoked by CCl4 as evidenced by inhibition of reduced
      glutathione depletion and lipid peroxidation as well as elevation of antioxidant
      enzyme superoxide dismutase (SOD). Further, PIN upregulated the nuclear factor
      erythroid 2 (NF-E2)-related factor 2 (Nrf2), thereby inducing the expression and
      activity of the cytoprotective enzyme hemeoxygenase-1 (HO-1). Moreover, PIN
      alleviated pro-inflammatory cytokines such as TNF-alpha via inhibiting nuclear
      factor-kappaB (NF-kappaB) activation. As markers of fibrosis, collagen and alpha
      SMA expression increased markedly in the CCl4 group and PIN prevented these
      alterations. In addition, PIN down-regulated TGFbeta1 and p-Smad2/3, thereby
      inhibiting TGFbeta1/Smad signaling pathway. CONCLUSION: These results suggest
      that PIN possess potent antifibrotic effects that can be explained on its
      antioxidant properties. It ameliorates oxidative stress and inflammation during
      induction of fibrogenesis via its ability to augment celular antioxidant
      defenses, activating Nrf2-mediated HO-1 expression and modulating NF-kappaB and
      TGF-beta1/Smad signaling pathway.

PMID- 29469033
TI  - Altered expression of the Cdk5 activator-like protein, Cdk5alpha, causes
      neurodegeneration, in part by accelerating the rate of aging.
AB  - Aging is the greatest risk factor for neurodegeneration, but the connection
      between the two processes remains opaque. This is in part for want of a rigorous
      way to define physiological age, as opposed to chronological age. Here, we
      develop a comprehensive metric for physiological age in Drosophila, based on
      genome-wide expression profiling. We applied this metric to a model of adult
      onset neurodegeneration, increased or decreased expression of the activating
      subunit of the Cdk5 protein kinase, encoded by the gene Cdk5alpha, the ortholog
      of mammalian p35. Cdk5alpha-mediated degeneration was associated with a 27-150%
      acceleration of the intrinsic rate of aging, depending on the tissue and genetic
      manipulation. Gene ontology analysis and direct experimental tests revealed that
      affected age-associated processes included numerous core phenotypes of
      neurodegeneration, including enhanced oxidative stress and impaired proteostasis.
      Taken together, our results suggest that Cdk5alpha-mediated neurodegeneration
      results from accelerated aging, in combination with cell-autonomous neuronal
      insults. These data fundamentally recast our picture of the relationship between
      neurodegeneration and its most prominent risk factor, natural aging.

PMID- 29469036
TI  - Incomplete Kawasaki Disease in an Infant with Cholangitis Post Kasai Surgery for
      Biliary Atresia.
AB  - Kawasaki's disease (KD) is a systemic vasculitis often seen with viral and
      bacterial infections. Cholangitis is a known complication in biliary atresia
      patients post Kasai Portoenterostomy (KP). However KD, in a biliary atresia
      patient post KP has not been previously reported. A 1 years old girl who had
      previously undergone a KP for BA, presented with cholangitis which was presumed
      to be caused by a previous enterobacter infection that she had 2 months ago.
      However, on treating the cholangitis, the patient developed fever again after ten
      days which persisted even after changing the antibiotics. By this time she also
      displayed three of five characteristic features of KD in form of fever,
      strawberry tongue and cervical adenopathy. Investigations showed high ESR, high
      CRP, thrombocythemia and dilated coronary vessels on echocardiography. Treatment
      with intravenous immunoglobulin (IVIG) and steroids caused the symptoms to
      subside.

PMID- 29469037
TI  - Hepatitis E Virus Genotype 1 Cases Imported to Portugal from India, 2016.
AB  - Hepatitis E in industrialized countries is mainly associated with genotype 3
      hepatitis E virus (HEV) and normally causes a sporadic self-limiting disease in
      immunocompetent individuals. Unlike genotype 3, genotypes 1 and 2 circulate in
      developing countries, produce severe disease and occur in the epidemic form.
      Hepatitis E occurring in travellers returning from endemic areas in developing
      countries is not a novel epidemiological occurrence, however the vast majority of
      cases remain to be genetically studied. The present study describes two cases of
      severe acute hepatitis E that required hospitalization for 6 and 9 days in two
      individuals of Indian nationality that had recently migrated to Portugal to work.
      The retrieved HEV sequences both belonged to genotype 1 and had a high degree of
      nucleotide sequence identity, clustering with strains isolated in India and
      Nepal, in 2013 and 2014. Confirmed HEV genotypes of increased pathogenicity like
      genotype 1 are being introduced into otherwise naive populations of
      industrialized countries such as European countries with consequences difficult
      to predict. As far as we know the present study is the first in Portugal to
      describe and genetically characterize imported cases of hepatitis E infection
      caused by HEV genotype 1.

PMID- 29469038
TI  - Bacterial Translocation Is Linked to Increased Intestinal IFN-gamma, IL-4, IL-17,
      and mucin-2 in Cholestatic Rats.
AB  - : Background and rationale for the study. Bacterial translocation is an important
      triggering factor of infection and mortality in cirrhosis. In a rat model using
      bile duct ligation (BDL), bacterial translocation appears within 24 h after
      ligation. The dynamic between TH1/TH2/TH17 cytokines and the integrity of the
      colonic mucosa in the context of cirrhosis is little known. This study aims to
      determine the link between bacterial translocation and intestinal inflammation in
      a cholestasis model. Additionally, alterations of the colonic mucus layer and the
      bacterial load were also addressed. RESULTS: Bacterial translocation detected by
      microbiological cultures and MALDI-TOF showed that Escherichia coli predominates
      in mesenteric lymph nodes of BDL rats. Intestinal bacterial load analyzed by qPCR
      indicates a dramatic Escherichia/Shigella overgrowth at 8 and 30 days post-BDL.
      IFN-gamma, IL-4, and IL-17 evaluated by Western blotting were increased at 8 and
      30 days in the small intestine. In the colon, in contrast, only IFN-gamma was
      significantly increased. The colonic mucus layer and mucin-2 expression
      determined by Alcian blue staining and immunohistochemistry surprisingly showed
      an increase in the mucus layer thickness related to increased mucin-2 expression
      during the entire process of liver damage. Hepatic enzymes, as well as collagen
      I, collagen III, TNF-alpha, and IL-6 liver gene expression were increased. In
      conclusion, bacterial overgrowth associated with bacterial translocation is
      linked to the over-expression of IFN-gamma, IL-4, IL-17 and mucin-2. These
      molecules might facilitate the intestinal permeability through exacerbating the
      inflammatory process and disturbing tight junctions, leading to the perpetuation
      of the liver damage.

PMID- 29469039
TI  - Impact of Cholangioscopy: Diagnosing Sclerosing Cholangitis-Associated Biliary
      Calculi not Detected Using MRI and Endoscopic Ultrasound.

PMID- 29469040
TI  - Long-Term Follow-up and Quantitative Hepatitis B Surface Antigen Monitoring in
      North American Chronic HBV Carriers.
AB  - INTRODUCTION: Quantitative hepatitis B surface antigen (qHBsAg) combined with HBV
      DNA may be useful for predicting chronic hepatitis B (CHB) activity and
      nucleoside analogue (NA) response. MATERIAL AND METHODS: In this retrospective
      cohort study we evaluated qHBsAg levels according to CHB disease phase and among
      patients on treatment. Random effect logistic regression analysis was used to
      analyze qHBsAg change with time in the NA-treated cohort. RESULTS: 545 CHB
      carriers [56% M, median age 48 y (IQR 38-59), 73% Asian] had qHBsAg testing. In
      the untreated group (44%), 8% were classified as immune tolerant, 10% immune
      clearance, 40% inactive, and 43% had HBeAg- CHB and the median HBsAg levels were
      4.6 (IQR 3.4-4.9), 4.0 (IQR 3.4-4.5), 2.9 (IQR 1.4-3.8), and 3.2 log IU/mL (IQR
      2.6-4.0), respectively; p < 0.001. In the NA-treated group (28% entecavir, 68%
      tenofovir, 4% lamivudine), no significant change in qHBsAg levels occurred with
      time, 19% of patients on long-term NA had sustained qHBsAg < 2 log10 IU/mL.
      CONCLUSION: qHBsAg titers were associated with CHB phase and remained stable in
      those on long-term NA. A significant number of treated patients had low-level
      qHBsAg, of which some may be eligible for treatment discontinuation without risk
      of flare.

PMID- 29469041
TI  - Natural Extracts Abolished Lipid Accumulation in Cells Harbouring non-favourable
      PNPLA3 genotype.
AB  - : Background & aims. G-allele of PNPLA3 (rs738409) favours triglycerides
      accumulation and steatosis. In this study, we examined the effect of quercetin
      and natural extracts from mushroom and artichoke on reducing lipid accumulation
      in hepatic cells. MATERIAL AND METHODS: Huh7.5 cells were exposed to oleic acid
      (OA) and treated with quercetin and extracts to observe the lipid accumulation,
      the intracellular-TG concentration and the LD size. Sterol regulatory element
      binding proteins-1 (SREBP-1), peroxisome proliferator-activated receptor
      (PPARalpha-gamma) and cholesterol acyltransferase (ACAT) gene expression levels
      were analysed. RESULTS: Quercetin decreased the intracellular lipids, LD size and
      the levels of intracellular-TG through the down-regulation of SREBP-1c, PPARgamma
      and ACAT1 increasing PPARalpha. The natural-extracts suppressed OA-induced lipid
      accumulation and the intracellular-TG. They down-regulate the hepatic lipogenesis
      through SREBP-1c, besides the activation of lipolysis through the increasing of
      PPARalpha expression. CONCLUSIONS: Quercetin and the aqueous extracts decrease
      intracellular lipid accumulation by down-regulation of lipogenesis and up
      regulation of lipolysis.

PMID- 29469042
TI  - More Evidence for the Genetic Susceptibility of Mexican Population to
      Nonalcoholic Fatty Liver Disease through PNPLA3.
AB  - BACKGROUND: The gene for patatin-like phospholipase domain containing 3 (PNPLA3)
      is associated with nonalcoholic fatty liver disease (NAFLD) development. We
      previously found that Mexican indigenous population had the highest frequency
      reported of the PNPLA3 148M risk allele. Further, we observed a relationship
      between M148M genotype with elevated ALT levels in individuals with normal
      weight, overweight and obese. We sought to investigate whether PNPLA3
      polymorphism is associated with NAFLD development in Mexicans. MATERIAL AND
      METHODS: We enrolled 189 Mexican patients with NAFLD and 201 healthy controls.
      Anthropometric, metabolic, and biochemical variables were measured, and rs738409
      (Ile148Met substitution) polymorphism was genotyped by sequencing. RESULTS:
      Logistic regression analysis, using a recessive model, suggested that PNPLA3
      polymorphism in Mexican population is significantly associated (OR = 1.711, 95%
      CI: 1.014-2.886; P = 0.044) with NAFLD. CONCLUSIONS: The PNPLA3 gene is
      associated with NAFLD in Mexican population. More studies are required to explain
      the high prevalence of PNPLA3 polymorphism in Mexican-Americans, Mexican-Indians,
      and Mexican-Mestizos.

PMID- 29469043
TI  - Viscoelastic Testing in Liver Disease.
AB  - Long thought to be hypocoagulable, new evidence suggests cirrhosis patients have
      "rebalanced" coagulation in the setting of decreased synthesis of both pro- and
      anti-coagulant factors. Traditional testing like PT/INR reflects only the
      decreased synthesis of pro-coagulant factors and thus does not correspond to
      bleeding or clotting risk in this population. In this review, we discuss the use
      of viscoelastic testing (VET), an assay of global hemostasis in cirrhosis
      patients. We describe the technique and interpretation of commercially available
      VET and assess the application of VET in both transplant and non-transplant
      cirrhosis populations. VET largely correlates well with traditional testing
      including platelet count and fibrinogen level, however, is potentially less
      accurate in patients with low fibrinogen levels. VET may be useful in identifying
      patients at higher risk of hypercoagulable complications post-transplant and
      reflects changes in hemostasis in decompensated patients. While VET has been
      associated with decreased transfusion support in multiple studies, the lack of
      bleeding in patients who avoided prophylactic transfusion suggests a "rescue"
      rather than prophylactic approach to transfusion may be ideal and further studies
      with a "rescue" arm are needed. Additional prospective studies of VET should
      include clinically relevant endpoints of bleeding and thrombosis.

PMID- 29469044
TI  - TCR Vbeta Usage of Peripheral Blood and Liver Infiltrating Lymphocytes in
      Patients with Chronic Hepatitis B.
AB  - INTRODUCTION: Chronic hepatitis B (CHB) is still a public health problem and its
      mechanism remains unclear. In this study, we detect the skewness of T cell
      receptor beta chain variable gene (TCR Vbeta) in peripheral blood lymphocytes
      (PBL) and the liver infiltrating lymphocytes (LIL) of patients with CHB; and hope
      to provide information for further research on the pathogenic mechanism of CHB.
      MATERIAL AND METHODS: Fifteen patients with CHB, ten healthy volunteers and three
      patients with liver cysts were recruited as the subjects. The usage of TCR Vbeta
      of PBL and LIL were measured and compared; the associations of the TCR Vbeta
      usage of PBL with some hematological indices, including human leukocyte antigen
      (HLA) alleles, percents of CD4+ and CD8+ T cells, sera levels of HBV-DNA and IFN
      gamma, were analyzed. RESULTS: In PBL, Vbeta12 and Vbeta13.1 were the highest
      predominant usage genes which usage frequencies were all 46.7%; Vbeta23 was the
      key limited usage gene (40.0%). In LIL, the mainly predominant and limited usage
      gene was Vbeta13.1 (73.3%) and Vbeta23 (46.7%), respectively. About half of the
      patients with CHB with HLA-DR9 or HLA-DR12 showed the predominant usage of
      Vbeta5.2 or Vbeta13.2. In patients with CHB, the percentage of CD4+ T cells was
      33.41 +/- 5.39 %, that of CD8+ T cells was 28.67 +/- 6.77 %; the concentration of
      IFN-gamma was 182.52 +/- 44.16 pg/mL. Compared to the healthy controls, there
      were significant differences for these data (P < 0.05). Neither ALT nor HBV-DNA
      was relative to the usage of TCR Vbeta. CONCLUSIONS: PBL and LIL share the common
      sknewness of TCR Vbeta genes, which probably relates to some hematological
      indices. However, the roles of such similarities and associations in the
      development of CHB need further study.

PMID- 29469045
TI  - Clinical Significance of Serum Adiponectin and Resistin Levels in Liver
      Cirrhosis.
AB  - INTRODUCTION: Adiponectin and resistin levels are increased in patients with
      cirrhosis, but it prognostic significance is unknown. We sought to investigate
      the factors associated with adiponectin and resistin levels and its clinical
      significance in patients with cirrhosis. MATERIALS AND METHODS: This was a
      prospective cohort study that included 122 subjects with cirrhosis who attended
      an outpatient clinic and were initially evaluated in 2012. Serum adiponectin and
      resistin levels were measured in samples collected in 2012 (adiponectin and
      resistin) and 2014 (adiponectin). Thirty healthy subjects served as a control
      group. RESULTS: Higher adiponectin (21.59 MU g/mL vs. 12.52 MUg/mL, P < 0.001)
      and resistin levels (3.83 ng/mL vs. 2.66 ng/mL, P < 0.001) were observed among
      patients with cirrhosis compared to controls. Patients classified as Child-Pugh
      B/C had higher adiponectin levels in relation to Child-Pugh A patients. At second
      measurement, adiponectin levels increased significantly in non-transplant
      patients and decreased in liver transplant recipients. Univariate Cox analysis
      showed that among patients with alcoholic liver disease, adiponectin levels were
      associated with lower transplant-free survival (HR = 1.034, 95% CI 1.006 - 1.062,
      P = 0.016). The transplant-free survival was significantly lower among patients
      with alcoholic liver disease and adiponectin >= 17 MUg/mL (26.55 months, 95% CI
      21.40-31.70) as compared to those with levels < 17 MUg/mL (33.76 months, 95% CI
      30.70-36.82) (P = 0.045). No relationship was found between the levels of
      resistin and survival. CONCLUSION: Adiponectin but not resistin levels were
      associated with intensity of liver dysfunction and worse prognosis in patients
      with alcoholic liver disease, suggesting a potential as a prognostic biomarker.

PMID- 29469046
TI  - Treatment of Type-1 Hepatorenal Syndrome with Pentoxifylline: A Randomized
      Placebo Controlled Clinical Trial.
AB  - INTRODUCTION: Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in
      patients with cirrhosis. Currently available medical therapies are largely
      ineffective, save for liver transplantation. We aimed to determine if
      pentoxifylline (PTX) therapy in addition to the standard of care of volume
      expansion with albumin and vasoconstriction with midodrine and octreotide (AMO)
      is safe and efficacious compared to AMO in HRS-1 treatment. MATERIAL AND METHODS:
      Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX
      or placebo was administered with AMO therapy for up to 14 days. The primary
      endpoint was HRS-1 resolution (serum creatinine <= 1.5 g/dL for > 24 h).
      Secondary endpoints were change in creatinine and MELD score, partial treatment
      response, 30-and 180-day overall and transplant free survival. RESULTS: Twelve
      subjects with mean age 58.9 +/- 6.2 years were enrolled and randomized. Mean MELD
      score was 26.5 +/- 7.4 and 58.3% were male. Overall cohort 30- and 180-day
      survival was 58.3% and 33.3% respectively. Two subjects underwent liver
      transplantation. HRS-1 resolution (16.7% vs. 16.7%, p = 1.000), partial treatment
      response (33.3% vs. 16.7%, p = 0.505), change in creatinine (+0.48 g/dL, 95% CI 
      0.49-1.46 vs. +0.03 g/dL, 95% CI -0.64- 0.70, p = 0.427), 30-day survival (66.6%
      vs. 50.0%, p = 0.558) and 180-day survival (50.0% vs. 16.7%, p = 0.221) were
      similar between the two groups. Serious adverse events necessitating treatment
      discontinuation were rare (n = 1, PTX). DISCUSSION: The addition of PTX to AMO in
      the treatment of HRS-1 is safe when compared to the current standard of care.
      Future large-scale prospective study to validate the efficacy of this treatment
      seems warranted.

PMID- 29469047
TI  - Racial, Ethnic, and Age Disparities in Incidence and Survival of Intrahepatic
      Cholangiocarcinoma in the United States; 1995-2014.
AB  - INTRODUCTION: Despite reports of increased incidence of intrahepatic
      cholangiocarcinoma (iCCA) in the United States, the impact of age or influences
      of race and ethnicity are not clear. Disparities in iCCA outcomes across various
      population subgroups also are not readily recognized due to the rarity of this
      cancer. We examined ethnic, race, age, and gender variations in iCCA incidence
      and survival using data from the Surveillance, Epidemiology, and End Results
      Program (1995-2014). MATERIALS AND METHODS: We assessed age-adjusted incidence
      rates, average annual percentage change in incidence, and hazard ratios (HRs)
      with 95% confidence intervals (CIs) for all-cause and iCCA-specific mortality.
      RESULTS: Overall, 11,127 cases of iCCA were identified, with an age-adjusted
      incidence rate of 0.92 per 100,000. The incidence rate increased twofold, from
      0.49 per 100,000 in 1995 to 1.49 per 100,000 in 2014, with an average annual rate
      of increase of 5.49%. The iCCA incidence rate was higher among persons age 45
      years or older than those younger than 45 years (1.71 vs. 0.07 per 100,000),
      among males than females (0.97 vs. 0.88 per 100,000) and among Hispanics than non
      Hispanics (1.18 vs. 0.89 per 100,000). Compared to non-Hispanics, Hispanics had
      poorer 5-year all-cause mortality (HR=1.11, 95%CI: 1.05-1.19) and poorer iCCA
      specific mortality (HR=1.15, 95%CI: 1.07-1.24). Survival rates were poor also for
      individuals age 45 years or older, men, Blacks, and American Indians/Alaska
      Natives. CONCLUSION: The results demonstrate ethnic, race, age and gender
      disparities in iCCA incidence and survival, and confirm continued increase in
      iCCA incidence in the United States.

PMID- 29469048
TI  - Results of Liver Transplantation for Hepatocellular Carcinoma in a Multicenter
      Latin American Cohort Study.
AB  - BACKGROUND AND AIMS: Heterogeneous data has been reported regarding liver
      transplantation (LT) for hepatocellular carcinoma (HCC) in Latin America. We
      aimed to describe treatment during waiting list, survival and recurrence of HCC
      after LT in a multicenter study from Latin America. MATERIAL AND METHODS:
      Patients with HCC diagnosed prior to transplant (cHCC) and incidentally found in
      the explanted liver (iHCC) were included. Imaging-explanted features were
      compared in cHCC (non-discordant if pre and post-LT were within Milan, discordant
      if pre-LT was within and post-LT exceeding Milan). RESULTS: Overall, 435 patients
      with cHCC and 92 with iHCC were included. At listing, 81% and 91% of cHCC
      patients were within Milan and San Francisco criteria (UCSF), respectively. Five
      year survival and recurrence rates for cHCC within Milan, exceeding Milan/within
      UCSF and beyond UCSF were 71% and 16%; 66% and 26%; 46% and 55%, respectively.
      Locoregional treatment prior to LT was performed in 39% of cHCC within Milan, in
      53% beyond Milan/within UCSF and in 83% exceeding UCSF (p < 0.0001). This
      treatment difference was not observed according to AFP values (<=100, 44%; 101
      1,000, 39%, and > 1,000 ng/mL 64%; p = 0.12). Discordant imaging-explanted data
      was observed in 29% of cHCC, showing lower survival HR 2.02 (CI 1.29; 3.15) and
      higher recurrence rates HR 2.34 when compared to AFP <100 ng/mL. Serum AFP >
      1,000 ng/mL at listing was independently associated with a higher 5-year
      recurrence rate and a HR of 3.24 when compared to AFP <100 ng/mL. CONCLUSION:
      Although overall results are comparable to other regions worldwide, pre-LT
      treatment not only considering imaging data but also AFP values should be
      contemplated during the next years.

PMID- 29469049
TI  - Safety and Efficacy of Laparoscopic Radiofrequency Ablation for Hepatic
      Hemangiomas: A Multicenter Retrospective Study.
AB  - INTRODUCTION: Radiofrequency ablation (RFA) is an effective and minimally
      invasive technique for the management of hepatic hemangiomas (HHs). This study
      aims to assess the safety and efficacy of laparoscopic RFA for HHs. MATERIAL AND
      METHODS: Forty-four patients with 50 hepatic hemangiomas (5-10 cm in diameter)
      undergoing laparoscopic RFA from January 2012 to May 2015 at three tertiary
      hospitals in China were retrospectively analyzed. RESULTS: Thirty-three patients
      with subcapsular hemangiomas were treated with a laparoscopic approach, and 11
      patients with lesions in the liver parenchyma were treated with a combined
      laparoscopy and an ultrasound-guided percutaneous approach. No conversion to open
      surgery or two-step surgery occurred during the study period. Patients with small
      hemangiomas (< 7 cm) required a significantly shorter operating time (71.1 +/-
      20.18 min vs. 106 +/- 23.55 min, p = 0.000) and fewer punctures compared with
      patients with large hemangiomas (> 7 cm) (4.61 +/- 1.09 vs. 6.73 +/-1.01, P <
      0.05). According to the Dindo-Clavien classification, 15 patients experienced 34
      Grade 1 complications, and two had complications of Grade 3a. All complications
      were resolved by conservative treatment. Forty-three (86.0%) HHs in 38 patients
      were completely ablated after RFA, and 7 (14.0%) HHs in 6 patients were
      incompletely ablated. All patients were followed up for 6-24 months (mean 15 +/-
      6 months). CONCLUSION: The data showed that laparoscopic RFA is an effective
      treatment for small (< 10 cm) HHs. While the incidence of postoperative
      complications remains high, the majority of complications are minor. Patients
      undergoing laparoscopic RFA for HHs, even for the small ones, should be carefully
      selected.

PMID- 29469050
TI  - Natural Extracts as Modifiers of Intracellular Lipid Handling.

PMID- 29469051
TI  - Nonalcoholic Fatty Liver Disease Progresses into Severe NASH when Physiological
      Mechanisms of Tissue Homeostasis Collapse.
AB  - Phenotypic modulation of NAFLD-severity by molecules derived from white
      (adipokines) and brown (batokines) adipose tissue may be important in inducing or
      protecting against the progression of the disease. Adipose tissue-derived factors
      can promote the progression of NAFLD towards severe histological stages (NASH
      fibrosis and NASHcirrhosis). This effect can be modulated by the release of
      adipokines or batokines that directly trigger an inflammatory response in the
      liver tissue or indirectly modulate related phenotypes, such as insulin
      resistance. Metabolically dysfunctional adipose tissue, which is often
      infiltrated by macrophages and crown-like histological structures, may also show
      impaired production of anti-inflammatory cytokines, which may favor NAFLD
      progression into aggressive phenotypes by preventing its protective effects on
      the liver tissue.

PMID- 29469052
TI  - Recent Advances in Hepatotoxicity of Non Steroidal Anti-Inflammatory Drugs.
AB  - Non-steroidal-anti-inflammatory drugs (NSAIDs) make a heterogenous pharmaco
      therapeutic class of drugs among the most used drugs worldwide with various
      indications, modes of administration and increasing automedication. NSAIDs can
      cause acute liver injury with variable severity. The recent identification of
      genetic markers might facilitate the diagnosis and the prediction of
      hepatotoxicity risk.

PMID- 29469053
TI  - Fontan-Associated Liver Disease: A Review.
AB  - Fontan-associated liver disease is a hepatic disorder arising from hemodynamic
      changes and systemic venous congestion following Fontan surgery. The histological
      changes produced in the liver are similar but not equivalent to those seen in
      other forms of cardiac liver disease. While the natural history of this form of
      liver disease is not well established, over time many Fontan patients develop
      portal hypertension-related complications such as ascites, variceal hemorrhage or
      encephalopathy. Fontan survivors also show an increased risk of hepatocellular
      carcinoma. Early diagnosis of advanced liver disease is mandatory for the
      prevention and treatment of complications such as hepatocellular carcinoma,
      esophageal varices and malnutrition. This review updates current knowledge of the
      pathophysiology and management of Fontan-associated liver disease including new
      diagnostic methods and treatments.

PMID- 29469054
TI  - Significance of the impact of motion compensation on the variability of PET image
      features.
AB  - In lung cancer, quantification by positron emission tomography/computed
      tomography (PET/CT) imaging presents challenges due to respiratory movement. Our
      primary aim was to study the impact of motion compensation implied by
      retrospectively gated (4D)-PET/CT on the variability of PET quantitative
      parameters. Its significance was evaluated by comparison with the variability due
      to (i) the voxel size in image reconstruction and (ii) the voxel size in image
      post-resampling. The method employed for feature extraction was chosen based on
      the analysis of (i) the effect of discretization of the standardized uptake value
      (SUV) on complementarity between texture features (TF) and conventional indices,
      (ii) the impact of the segmentation method on the variability of image features,
      and (iii) the variability of image features across the time-frame of 4D-PET.
      Thirty-one PET-features were involved. Three SUV discretization methods were
      applied: a constant width (SUV resolution) of the resampling bin (method RW), a
      constant number of bins (method RN) and RN on the image obtained after histogram
      equalization (method EqRN). The segmentation approaches evaluated were
      40[Formula: see text] of SUVmax and the contrast oriented algorithm (COA).
      Parameters derived from 4D-PET images were compared with values derived from the
      PET image obtained for (i) the static protocol used in our clinical routine (3D)
      and (ii) the 3D image post-resampled to the voxel size of the 4D image and PET
      image derived after modifying the reconstruction of the 3D image to comprise the
      voxel size of the 4D image. Results showed that TF complementarity with
      conventional indices was sensitive to the SUV discretization method. In the
      comparison of COA and 40[Formula: see text] contours, despite the values not
      being interchangeable, all image features showed strong linear correlations (r  >
      0.91, [Formula: see text]). Across the time-frames of 4D-PET, all image features
      followed a normal distribution in most patients. For our patient cohort, the
      compensation of tumor motion did not have a significant impact on the
      quantitative PET parameters. The variability of PET parameters due to voxel size
      in image reconstruction was more significant than variability due to voxel size
      in image post-resampling. In conclusion, most of the parameters (apart from the
      contrast of neighborhood matrix) were robust to the motion compensation implied
      by 4D-PET/CT. The impact on parameter variability due to the voxel size in image
      reconstruction and in image post-resampling could not be assumed to be
      equivalent.

PMID- 29469055
TI  - A head motion estimation algorithm for motion artifact correction in dental CT
      imaging.
AB  - A small head motion of the patient can compromise the image quality in a dental
      CT, in which a slow cone-beam scan is adopted. We introduce a retrospective head
      motion estimation method by which we can estimate the motion waveform from the
      projection images without employing any external motion monitoring devices. We
      compute the cross-correlation between every two successive projection images,
      which results in a sinusoid-like displacement curve over the projection view when
      there is no patient motion. However, the displacement curve deviates from the
      sinusoid-like form when patient motion occurs. We develop a method to estimate
      the motion waveform with a single parameter derived from the displacement curve
      with aid of image entropy minimization. To verify the motion estimation method,
      we use a lab-built micro-CT that can emulate major head motions during dental CT
      scans, such as tilting and nodding, in a controlled way. We find that the
      estimated motion waveform conforms well to the actual motion waveform. To further
      verify the motion estimation method, we correct the motion artifacts with the
      estimated motion waveform. After motion artifact correction, the corrected images
      look almost identical to the reference images, with structural similarity index
      values greater than 0.81 in the phantom and rat imaging studies.

PMID- 29469056
TI  - Stress induced magnetic-domain evolution in magnetoelectric composites.
AB  - Local observation of the stress mediated magnetoelectric (ME) effect in
      composites has gained a great deal of interest over the last decades. However,
      there is an apparent lack of rigorous methods for a quantitative characterization
      of the ME effect at the local scale, especially in polycrystalline
      microstructures. In the present work, we address this issue by locally probing
      the surface magnetic state of barium titante-hexagonal barium ferrite (BaTiO3
      BaFe12O19) ceramic composites using magnetic force microscopy (MFM). The effect
      of the piezoelectrically induced local stress on the magnetostrictive component
      (BaFe12O19, BaM) was observed in the form of the evolution of the magnetic
      domains. The local piezoelectric stress was induced by applying a voltage to the
      neighboring BaTiO3 grains, using a conductive atomic force microscopy tip. The
      resulting stochastic evolution of magnetic domains was studied in the context of
      the induced magnetoelastic anisotropy. In order to overcome the ambiguity in the
      domain changes observed by MFM, certain generalizations about the observed MFM
      contrast are put forward, followed by application of an algorithm for extracting
      the average micromagnetic changes. An average change in domain wall thickness of
      50 nm was extracted, giving a lower limit on the corresponding induced
      magnetoelastic anisotropy energy. Furthermore, we demonstrate that this induced
      magnetomechanical energy is approximately equal to the K1 magnetocrystalline
      anisotropy constant of BaM, and compare it with a modeled value of applied
      elastic energy density. The comparison allowed us to judge the quality of the
      interfaces in the composite system, by roughly gauging the energy conversion
      ratio.

PMID- 29469057
TI  - Localized surface plasmon enhanced deep UV-emitting of AlGaN based multi-quantum
      wells by Al nanoparticles on SiO2 dielectric interlayer.
AB  - In this paper, we report a 2.6-fold deep ultraviolet emission enhancement of
      integrated photoluminescence (PL) intensity in AlGaN-based multi-quantum wells
      (MQWs) by introducing the coupling of local surface plasmons from Al
      nanoparticles (NPs) on a SiO2 dielectric interlayer with excitons and photons in
      MQWs at room temperature. In comparison to bare AlGaN MQWs, a significant 2.3
      fold enhancement of the internal quantum efficiency, from 16% to 37%, as well as
      a 13% enhancement of photon extraction efficiency have been observed in the MQWs
      decorated with Al NPs on SiO2 dielectric interlayer. Polarization-dependent PL
      measurement showed that both the transverse electric and transverse magnetic mode
      were stronger than the original intensity in bare AlGaN MQWs, indicating a strong
      LSPs coupling process and vigorous scattering ability of the Al/SiO2 composite
      structure. These results were confirmed by the activation energy of non-radiative
      recombination from temperature-dependent PL measurement and the theoretical three
      dimensional finite difference time domain calculations.

PMID- 29469058
TI  - Straightforward measurement of anisotropic thermal properties of a Bi2Se3 single
      crystal.
AB  - We demonstrate here a simple measurement protocol which allows the thermal
      properties of anisotropic crystalline materials to be determined. This protocol
      is validated by the measurement of Bi2Se3, a layered material consisting of
      covalently bonded sheets with weak van der Waals bonds between each layer, which
      has highly anisotropic thermal properties. Thermoreflectance microscopy
      measurements were carried out on a single-crystal Bi2Se3 sample, firstly on the
      bare sample and then after capping with a 100 nm thick gold layer. Whereas on the
      bare sample lateral heat diffusion is dominated by the in-plane thermal
      diffusivity, on the metal-capped substrate heat diffusion perpendicular to the
      sample surface dominates. Using a simple theoretical model, we show how this
      double measurement protocol allows the anisotropic thermal conductivity
      coefficients of bulk Bi2Se3 to be evaluated.

PMID- 29469059
TI  - Low-friction nanojoint prototype.
AB  - High surface energy of individual nanostructures leads to high adhesion and
      static friction that can completely hinder the operation of nanoscale systems
      with movable parts. For instance, silver or gold nanowires cannot be moved on
      silicon substrate without plastic deformation. In this paper, we experimentally
      demonstrate an operational prototype of a low-friction nanojoint. The movable
      part of the prototype is made either from a gold or silver nano-pin produced by
      laser-induced partial melting of silver and gold nanowires resulting in the
      formation of rounded bulbs on their ends. The nano-pin is then manipulated into
      the inverted pyramid (i-pyramids) specially etched in a Si wafer. Due to the
      small contact area, the nano-pin can be repeatedly tilted inside an i-pyramid as
      a rigid object without noticeable deformation. At the same time in the absence of
      external force the nanojoint is stable and preserves its position and tilt angle.
      Experiments are performed inside a scanning electron microscope and are supported
      by finite element method simulations.

PMID- 29469060
TI  - Single-fabrication-step Ge nanosphere/SiO2/SiGe heterostructures: a key enabler
      for realizing Ge MOS devices.
AB  - We report channel and strain engineering of self-organized, gate-stacking
      heterostructures comprising Ge-nanosphere gate/SiO2/SiGe-channels. An exquisitely
      controlled dynamic balance between the concentrations of oxygen, Si, and Ge
      interstitials was effectively exploited to simultaneously create these
      heterostructures in a single oxidation step. Process-controlled tunability of the
      channel length (5-95 nm diameters for the Ge-nanospheres), gate oxide thickness
      (2.5-4.8 nm), as well as crystal orientation, chemical composition and strain
      engineering of the SiGe-channel was achieved. Single-crystalline (100) Si1-x Ge x
      shells with Ge content as high as x = 0.85 and with a compressive strain of 3%,
      as well as (110) Si1-x Ge x shells with Ge content of x = 0.35 and corresponding
      compressive strain of 1.5% were achieved. For each crystal orientation, our high
      Ge-content, highly-stressed SiGe shells feature a high degree of crystallinity
      and thus, provide a core 'building block' required for the fabrication of Ge
      based MOS devices.

PMID- 29469061
TI  - A self-resetting spiking phase-change neuron.
AB  - Neuromorphic, or brain-inspired, computing applications of phase-change devices
      have to date concentrated primarily on the implementation of phase-change
      synapses. However, the so-called accumulation mode of operation inherent in phase
      change materials and devices can also be used to mimic the integrative properties
      of a biological neuron. Here we demonstrate, using physical modelling of
      nanoscale devices and SPICE modelling of associated circuits, that a single phase
      change memory cell integrated into a comparator type circuit can deliver a basic
      hardware mimic of an integrate-and-fire spiking neuron with self-resetting
      capabilities. Such phase-change neurons, in combination with phase-change
      synapses, can potentially open a new route for the realisation of all-phase
      change neuromorphic computing.

PMID- 29469062
TI  - Fine structure of metal-insulator transition in EuO resolved by doping
      engineering.
AB  - Metal-insulator transitions (MITs) offer new functionalities for nanoelectronics.
      However, ongoing attempts to control the resistivity by external stimuli are
      hindered by strong coupling of spin, charge, orbital and lattice degrees of
      freedom. This difficulty presents a quest for materials which exhibit MIT caused
      by a single degree of freedom. In the archetypal ferromagnetic semiconductor EuO,
      magnetic orders dominate the MIT. Here we report a new approach to take doping
      under control in this material on the nanoscale: formation of oxygen vacancies is
      strongly suppressed to exhibit the highest MIT resistivity jump and
      magnetoresistance among thin films. The nature of the MIT is revealed in Gd doped
      films. The critical doping is determined to be more than an order of magnitude
      lower than in all previous studies. In lightly doped films, a remarkable thermal
      hysteresis in resistivity is discovered. It extends over 100 K in the
      paramagnetic phase reaching 3 orders of magnitude. In the warming mode, the MIT
      is shown to be a two-step process. The resistivity patterns are consistent with
      an active role of magnetic polarons-formation of a narrow band and its thermal
      destruction. High-temperature magnetic polaron effects include large negative
      magnetoresistance and ferromagnetic droplets revealed by x-ray magnetic circular
      dichroism. Our findings have wide-range implications for the understanding of
      strongly correlated oxides and establish fundamental benchmarks to guide
      theoretical models of the MIT.

PMID- 29469063
TI  - A study of serum vascular endothelial growth factor in infantile hemangiomas.
AB  - Background: Though infantile hemangiomas are the most common benign tumor of
      infancy, their etiopathogenesis is not fully understood. Some studies report a
      diagnostic role for vascular endothelial growth factor (VEGF), but such studies
      are lacking from India. Aims: To study the clinicoepidemiological profile of
      infantile hemangiomas, to estimate and compare the serum levels of VEGF in
      infantile hemangiomas and controls, and to determine correlations between serum
      levels of VEGF and growth characteristics of infantile hemangiomas. Methods: A
      hospital-based, cross-sectional study was carried out on 30 clinically diagnosed
      cases of infantile hemangioma and 30 controls presenting with other disorders.
      VEGF levels were recorded for both cases and controls by the sandwich enzyme
      linked immunosorbent assay (ELISA) technique. Results were analyzed using SPSS
      version 20.0, and their significance determined using appropriate tests. Results:
      Mean serum VEGF level in the cases was 216.8 +/- 49.2 pg/ml while in the control
      group it was 115.1 +/- 43.1 pg/ml (P < 0.0001). There were no statistically
      significant correlations between serum VEGF levels and sex or size, phase of
      growth, morphological variants or ulceration of lesions. Limitations: Our sample
      was not large enough to draw clinically applicable conclusions. An adequate
      sample size could not be achieved because of low incidence of the disease, and
      resource and time constraints. Conclusions: The mean value of serum VEGF in the
      study group was significantly higher than that in the control group, suggesting
      that serum VEGF can serve as a diagnostic marker of infantile hemangiomas. Mean
      serum VEGF was higher in proliferative lesions than in involuting lesions,
      indicating that it may also be useful as a prognostic serological marker in cases
      of infantile hemangioma.

PMID- 29469064
TI  - From the new editors.....

PMID- 29469065
TI  - Neoadjuvant chemotherapy for unresectable oral cancers: Optimizing outcomes?

PMID- 29469066
TI  - Clinico-pathological profile of colorectal cancer in first two decades of life: A
      retrospective analysis from tertiary health center.
AB  - AIM: This retrospective observational study was done to analyze age, gender, site
      of primary tumor and histological characterstics in patients of colorectal
      carcinoma in the first two decades of life. MATERIAL AND METHOD: A total of 373
      patients of colorectal patients were registered in the Department of Radiation
      Oncology from January 2010 to December 2015. Patients who were <20 years of age
      were analyzed for clinicopathological characteristic. RESULTS: In our study, a
      total of 29 out of 373 patients (7.75%) were <=20 years. Male to female
      distribution was 2.2:1. Younger age group presented with advanced Stage III and
      IV 58.62% and 10.34% patients, respectively. Only 9 (30.5%) patients were of
      Stage I and II. The most common involved site was rectum in 21 (72.41%) patients,
      followed by rectosigmoid involvement in 5 (17.24%). CONCLUSIONS: Colorectal
      carcinoma in young adults is usually locally advanced or metastatic. Therefore,
      the diagnosis of CRC should be done at early and curable stage. Bleeding per
      rectum in a younger age group should not be ignored but must be properly
      evaluated.

PMID- 29469067
TI  - Histopathologic review of 400 biopsies and resection specimens of trunk and
      extremity-based soft tissue tumors.
AB  - AIMS: To review various pathologic parameters in diagnosed cases of trunk and
      extremity-based soft tissue tumors (STTs), in order to identify concordance rate
      between initial biopsy and resection specimen and discrepancies between initial
      and review diagnosis, by a specialist pathologist. MATERIALS AND METHODS: Over a
      2-year-period, 400 retrospectively diagnosed STTs (553 specimens) including
      referral and "in-house" cases were studied. The reviewing specialist pathologist
      was blinded to the initial diagnoses. Discordances including discrepancies and
      deficiencies were defined as major and minor. Major discrepancies included those
      that could lead to significant treatment changes. True discrepancies were those
      related to sampling issues between the biopsies and resection specimens.
      Deficiencies relating to tumor subtyping, sarcoma grading, documentation of tumor
      size, and marginal status (in resections) were subdivided as major and minor.
      RESULTS: Most cases (328, 82%) were sarcomas (most common, synovial sarcoma; most
      common Stage, III), followed by benign tumors (36, 9%) (most common, schwannoma)
      and intermediate malignancies (32, 8%) (most common, fibromatosis). Within STTs,
      liposarcomas, neural tumors, and undifferentiated pleomorphic sarcomas were
      relatively more frequently associated with discrepancies. Percentage of cases
      with major discordances between the referral reports (100 cases) and review
      diagnosis was 60%. Percentage of cases with major discordances between the
      specialist and other oncopathologists was 11%. True discrepancies were observed
      in 20 (5%) cases. The association of type of specimen with the rate of
      discordance was not significant (P = 0.114). CONCLUSIONS: Diagnoses of STTs are
      fraught with errors mostly from general pathologists, followed by nonspecialist
      oncopathologists. These findings reinforce the need for reporting of STTs,
      especially sarcomas, by specialist pathologists.

PMID- 29469068
TI  - Reirradiation for recurrent primary central nervous system tumors: Eight-year
      audit from a tertiary cancer care center in South India.
AB  - BACKGROUND: Radiation therapy is a major treatment option in the management of
      primary central nervous system (CNS) tumors, though recurrences after primary
      treatment, especially in high-grade glial tumors, is a challenge for treating
      physician. Advances in the field of radiation have made reirradiation a feasible
      option in recurrent CNS tumors. MATERIALS AND METHODS: Details of patients with
      primary CNS lesions who presented between 2009 and 2016, with recurrent CNS
      lesions, and who were treated with reirradiation were retrieved from electronic
      medical records, as a departmental audit, and the outcome was analyzed. RESULTS:
      A total of 33 patients received reirradiation. Median follow-up was 112.7 months.
      Median age at presentation was 36 years. On completing initial treatment, 42.4%
      had no residual disease. Median time to symptomatic recurrence was 51.33 months.
      For reirradiation, stereotactic radiotherapy was used in 27.3%, stereotactic
      radiosurgery in 12.1%, and intensity-modulated radiation therapy in 36.4%. Mean
      cumulative 2 Gy equivalent dose (EQD2) was 111.00 +/- 15.287 Gy. At the last
      follow-up, 57.6% of patients were alive, and 27.3% had succumbed to the disease.
      Median OS was 187.67 months. Three-year survival after reirradiation was 74.1%.
      CONCLUSION: Our study is probably one of the first from the Indian subcontinent
      analyzing a series of reirradiation in primary CNS tumors. Our survival
      subsequent to reirradiation is comparable to that in available literature; which
      are also mostly retrospective. Our analysis also substantiates that younger
      patients, longer intervals between the two sets of radiation and biologically
      effective dose <100 Gy and EQD2Cumulativeof <100 Gy are factors that favorably
      improve the survival after reirradiation as has been shown in literature.

PMID- 29469069
TI  - Retrospective analysis of patients with relapsed or refractory testicular
      nonseminous germ cell tumors treated with autologous stem cell transplantation.
AB  - BACKGROUND AND AIM: About 20-25% of the testicular germ cell tumors (TGCT) are
      relapsed or refractory after first line therapy and optimal treatment for this
      group is poorly defined. We aimed to analyze the efficacy and safety of
      autologous stem cell transplantation (ASCT) in this patient group.Material and.
      METHODS: 19 patients with 28 ASCT were retrospectively analyzed. All the patients
      were treated with BEP (Bleomycin, etoposide, cisplatin) as first line therapy and
      TIP(paclitexalifosfamide, cisplatin) was given as salvage chemotherapy. Stem cell
      collection was performed with TIP and granulocyte stimulating factor. ASCT was
      performed with carboplatin(700mg/m2) and etoposite(750mg /m 2). The results were
      provided as median(min-max). P<0.05 was accepted as statistical significant
      level. RESULTS: After ASCT, complete(CR) and partial remission (PR) rates were
      47.3% and 31 .5% respectively. The median overall survival(OS) and progression
      free survival (PFS) were 18(0-37.4 months) and 7(0-15months) months respectively.
      Estimated 2-year OS was 47.4% and PFS was 35.3%. Grade 3/4 toxicities including
      diarrhea, mucositis, and toxic hepatitis were observed in 5 patients. Only one
      patient died due to complication of transplantation. CONCLUSION: Although the
      number of the patients in this study is limited, ASCT seems to be a safe and
      effective treatment modality in relapsed refractory non-seminomatousTGCT with an
      acceptable OS, PFS and mortality rates.

PMID- 29469070
TI  - Utilization of pelvic lymph node dissection in patients undergoing robot-assisted
      radical prostatectomy in India versus the United States - A Vattikuti Collective
      Quality Initiative database analysis.
AB  - BACKGROUND: The utilization and extent of pelvic lymph node dissection (PLND)
      varies depending on the disease and practice patterns. AIMS: This study compares
      practice patterns in utilization of PLND between Indian and United States (US)
      practices. SETTINGS AND DESIGN: We focused on 415 patients (204 India; 211 US)
      prostate cancer patients treated with robot-assisted radical prostatectomy,
      between 2015 and 2016, within the Vattikuti Collective Quality Initiative
      database. SUBJECTS AND METHODS: Utilization of PLND and number of nodes removed
      were evaluated for the entire cohort, and after stratifying for Country of
      treatment and D'Amico risk groups. Logistic regression tested the relationship
      between PLND and country of treatment, after adjusting for disease risk. RESULTS:
      Indian patients had a higher risk distribution (D'Amico high-risk 53.4% in India
      vs. 27% in the US; P< 0.001) compared to their US counterparts. Overall, 193/204
      (94.6%) Indian patients underwent PLND versus 181/211 (85.8%) US patients (P =
      0.003). When stratified based on disease risk, PLND was performed more frequently
      in Indian patients with low-risk disease (81.0% vs. 41.4%,P= 0.008), but not in
      those with intermediate and high-risk disease. On multivariable analysis, Indian
      patients had a 2.57-fold higher probability of undergoing PLND than their US
      counterparts (P = 0.02). The analysis of the number of lymph nodes removed showed
      similar trends. CONCLUSIONS: Indian patients are more likely to undergo PLND than
      US patients. This is, especially true for patients with low-risk disease, who are
      unlikely to benefit from this procedure. Efforts should focus on optimizing the
      utilization of PLND, and deliver it only when there is clinical indication.

PMID- 29469071
TI  - Microsatellite Instability in Chronic Myeloid Leukemia using D17S261 and D3S643
      markers: A Pilot Study in Gujarat Population.
AB  - CONTEXT: Tumor progresses through a series of genetic alterations that involve
      proto-oncogenes and tumor suppressor genes - the gatekeeper, caretakers, and
      landscaper genes. Microsatellites are short tandem repeat sequences, present over
      the span of human genome and are known to be variable at multiple loci due to
      errors in DNA Mismatch Repair machinery. AIM: The present study was aimed to
      evaluate the association between Microsatellite Instability (MSI) and evolution
      of Chronic Myeloid Leukemia (CML) - genetically a rare event but profound in this
      pilot study. SETTINGS AND DESIGNS: We explore the possibility of MSI in primary
      CML patients confirmed by t(9;22) using capillary electrophoresis. Fifteen CML
      patients and healthy individual samples, respectively, were used to study the
      markers D17S261 and D3S643. MATERIALS AND METHODS: The DNA was amplified using
      tagged and nontagged primers and further subjected to bioanalysis and fragment
      analysis. RESULTS: While the results from bioanalyzer fluctuated, fragment
      analysis indicated the presence of microsatellite variability in 80% of the
      patients' samples as compared to no MSI in normal individuals for both the
      markers. CONCLUSION: These findings suggest that MSI is a genetic event that may
      have a role in CML progression or evolution. Further studies are warranted to
      understand the plausible underlying causes.

PMID- 29469072
TI  - Long-term outcome of diffuse large B-cell lymphoma: Impact of biosimilar
      rituximab and radiation.
AB  - INTRODUCTION: Rituximab (R)-CHOP improves survival over CHOP in diffuse large B
      cell lymphoma (DLBCL). The availability of biosimilar rituximab in India has
      increased access of this drug. We report on the impact of treatment on outcomes
      with special emphasis on the impact of biosimilar rituximab and radiation.
      METHODS: Outcomes of adults (age 15-60 years) treated with CHOP+/- Rituximab
      radiation were analyzed retrospectively to look at baseline features, treatment,
      and event-free and overall survival (EFS and OS). RESULTS: In the period 2000
      2013, 444 patients (median age 47 years: 15-60; males: 288 [65%]; Stage III/IV:
      224 [50%]; age-adjusted international prognostic index [aaIPI] Score 2 or 3 in
      50%) received either CHOP (n = 325 [73%]) or RCHOP (n = 119 [27%]) therapy.
      Biosimilar rituximab and the original were used in 95 (80%) and 24 (20%)
      patients, respectively. Radiation was given in 134 (30%) patients (Stages I and
      II, 100/220 [45%] and Stages III and IV, 34/224 [15%]). After a median follow-up
      of 46 (0.2-126) months, the 5-year EFS and OS were 59% and 68%, respectively. The
      factors predicting inferior EFS and OS were age> 40 years, performance status 2
      4, Stage III/IV, hemoglobin <12 g/dL, the aaIPI Score 2 or 3, and nonuse of
      rituximab and radiation. Radiation used in early stage disease benefitted all
      subgroups regardless of bulky disease, use of rituximab, or the number of cycles
      of chemotherapy. Addition of rituximab improved survival across all categories of
      aaIPI. CONCLUSION: Availability of biosimilar rituximab has increased access and
      survival of patients with DLBCL in India. Radiotherapy improved outcomes in early
      stages.

PMID- 29469073
TI  - ROS1 rearranged nonsmall cell lung cancer and crizotinib: An Indian experience.
AB  - ROS1 rearrangement acts as a driver mutation in 1-2% of NSCLC. Crizotinib is
      approved in this situation both in treatment naive and pre-treated patients. Here
      we report our experience with crizotinib in patients with advanced NSCLC
      harbouring ROS1 rearrangement. Eleven patients were included in our study. More
      than half of our patients had associated comorbidities and one fourth of them had
      a compromised performance status. Out of 11 patients, 5 of them were exposed to
      crizotinib .The response rates among crizotinib treated patients was 80%. With a
      median follow up of 9 months, median PFS and OS were 5.4 months and 8.5 months
      respectively for the entire population. Analyzing the outcomes separately ,
      median PFS and OS was not reached for those who received crizotinib compared to
      median PFS of 2.5 months and median OS of 4.2 months in those who were not
      exposed to crizotinib. The difference was statistically significant. Estimated 1
      year OS was 80% for those who received crizotinib compared to 18% for who did not
      receive crizotinib. In conclusion, crizotinib is effective with acceptable side
      effect profile in patients with ROS1 rearranged NSCLC in our population.

PMID- 29469074
TI  - Perioperative complications of esophagectomy: Postneoadjuvant treatment versus
      primary surgery - Our experience and review of literature.
AB  - AIMS: : To compare perioperative complications in esophagectomy after neoadjuvant
      therapy v/s primary surgery. SETTINGS AND DESIGN: : Retrospective analysis of
      perioperative complications in a prospectively maintained data base of patients
      who underwent esophagectomy as Primary surgery or after neoadjuvant therapy was
      done. METHODS AND MATERIAL: : 238 cases of esophagectomies performed for
      esophageal carcinoma were analysed and compared, out of which 125(52.5%) were
      given neoadjuvant therapy followed by surgery and 113(47.5%) underwent primary
      surgery. Surgical procedure was standard for both the groups. All the cases were
      analysed for perioperative complications. STATISTICAL ANALYSIS USED: : Data was
      analysed using Open Epi soft ware. Association between the two study group was
      assessed with Chi square test. RESULTS: : On comparison, both the groups were
      comparable in demographic profile and type of surgery performed. However, tumour
      stage was higher for cases who received neoadjuvant therapy as expected. On
      analysis there was no significant difference in overall morbidity and 30 days
      mortality. CONCLUSIONS: : Neoadjuvant Chemo/chemoradiotherapy is a feasible
      option in esophageal carcinoma without increase in incidence of peri operative
      morbidity or mortality.

PMID- 29469075
TI  - Paralingual and sublingual space invasion in magnetic resonance imaging of
      squamous cell carcinoma of anterior two-thirds of tongue: Is there a prognostic
      significance? A prospective evaluation.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) in tumors of anterior two-thirds of
      tongue has a significant role in assessing different tumor parameters, and in
      prognosticating. AIM: This prospective study conducted in a tertiary cancer care
      center, focused on patients with squamous cell carcinoma of anterior two-thirds
      of tongue. The significance of invasion of paralingual and sublingual spaces in
      relation to the pathological grade of these tumors, and its predictive value in
      pathological nodal involvement were analyzed. MATERIALS AND METHODS: All
      consecutive patients with the required inclusion criteria were accrued. Imaging
      was done with 3 Tesla MRI and invasion of sublingual and paralingual spaces were
      accurately assessed. Data elucidated were tabulated and analysed using IBM SPSS
      version 20.0. Chi-square test, nonparametric correlation using Spearman's Rho
      correlation, and two-independent sample test using Mann-Whitney's U-test were
      used to arrive at correlations between the imaging and histopathological
      parameters. RESULTS: Sixty-three patients were analyzed. Mean age was 52.3 +/-
      11.45 years. 74.6% were males. MRI showed sublingual space invasion in 47.6%.
      18/28 with and 11/33 without invasion had node positivity. Paralingual space
      involvement was observed in 31.7% of patients. Thirteen of these and 16/43 with
      no involvement had positive cervical nodes. No statistically significant
      correlation was observed. CONCLUSION: This prospective study did not establish
      any statistically sound correlation, and robust data are lacking to support newer
      parameters such as sublingual space and paralingual space as probable predictors
      of cervical nodal involvement, and for prognostication.

PMID- 29469076
TI  - Quality of life outcome measures using University of Washington questionnaire
      version 4 in early T1/T2 anterior tongue cancers with and without radiotherapy: A
      cross-sectional study.
AB  - CONTEXT: To evaluate the quality of life (QOL) outcome measures in disease-free
      survivors of pathological T1/T2 tongue cancers and to compare QOL in patients
      treated with only surgery and with adjuvant treatment. SETTINGS AND DESIGN: Cross
      sectional survey. PATIENTS AND METHODS: All pathological T1/T2 anterior tongue
      cancer cases with follow-up from January 2011 till December 2015, who had
      locoregionally controlled disease with a minimum disease-free survival period of
      1 year, were included in the study. RESULTS: A total of 36 patients, 28 are males
      and 8 are females with an age range of 24-66 years (median age of 43) were
      enrolled in the study. The patients were divided into two groups with (n = 26)
      and without adjuvant postoperative radiotherapy (RT) (n = 10) and the University
      of Washington-QOL questionnaire version 4 for physical and social domains, global
      questions and three important domains were analyzed. On the physical and social
      domain scores, the surgery-alone group outscored the combined modality group on
      all scales and the differences were statistically significant for specific
      physical domains such as saliva (0.0001), taste (P = 0.0001), chewing (P =
      0.0004), swallowing (P = 0.0026), and social domains such as mood (0.0001), pain
      (P = 0.0001), and shoulder function (P = 0.0061). The overall global QOL scores
      were also better for the surgical group compared with group which received
      adjuvant RT but was not statistically significant. All patients chose saliva as
      their top priority domain in the group which received radiation, and 60% chose
      "swallowing ability" as the preferred top priority domain in the only surgical
      group. CONCLUSIONS: Although locoregional control and disease-free survival are
      the major treatment-related endpoints for cancer management, QOL outcome measures
      have to assess to determine the impact of a treatment modality on patients well
      being and for better rehabilitation of cancer-free patients.

PMID- 29469077
TI  - Carboplatin-based concurrent chemoradiation therapy in locally advanced head and
      neck cancer patients who are unfit for cisplatin therapy.
AB  - BACKGROUND: Cisplatin-based chemoradiation (CTRT) is the standard of care in
      locally advanced head and neck cancers. Limited treatment options are available
      in patients unfit for cisplatin. AIMS: This audit was carried out to study the
      toxicities, tolerance, and outcomes of carboplatin-based CTRT in patients who are
      not eligible for cisplatin. MATERIALS AND METHODS: A total of 63 locally advanced
      head and neck cancer patients treated between January 2011 and October 2015 were
      administered carboplatin-based CTRT. The dose of carboplatin was equivalent to
      area under the curve equivalent to 2 administered once a week for a maximum of 7
      cycles. Toxicity was coded as per the CTCAE version 4.03. SPSS software version
      16 was used for statistical analysis. STATISTICAL ANALYSIS: Descriptive
      statistics was performed. Progression-free survival (PFS) and overall survival
      (OS) were estimated by Kaplan-Meier survival analysis. Cox proportional hazard
      model was used for identifying factors affecting PFS and OS. RESULTS: The reasons
      for patients being unfit for cisplatin were low serum creatinine clearance in 41
      (65.07%), sensorineural hearing loss in 18 (28.57%), uncontrolled medical
      comorbidities in 3 (4.76%), and old age in 1 patient (1.6%). 53 patients (84.1%)
      completed planned radiotherapy. The median number of chemotherapy cycles
      administered was 6. Grade 3-4 toxicities were seen in 32 patients (50.8%). The
      median OS and PFS were 28 months (95% confidence interval [CI]: 20.9-34.6 months)
      and 17 months (95% CI: 08.2-25.7 months), respectively. Age was the only factor
      significantly affecting OS and PFS. CONCLUSION: Carboplatin-based CTRT is well
      tolerated in patients unfit for cisplatin and seems to have superior outcomes
      than those reported in radical radiotherapy studies.

PMID- 29469078
TI  - Barriers affecting adherence to radiation treatment and strategies to overcome
      those barriers.
AB  - BACKGROUND: The WHO defines adherence as the extent to which a patient's behavior
      coincides with recommendations from a health-care provider. Nonadherence to
      cancer treatment has a major impact on the therapeutic outcome. AIM OF THE STUDY:
      To assess the prevalence of nonadherence to radiation regimen and to analyze the
      factors that affect adherence to cancer treatment. MATERIALS AND METHODS:
      Patients receiving radiation treatment in our hospital were screened for
      adherence to appointment keeping and to the prescribed radiation regimen and
      patients who had unplanned treatment breaks during treatment were interviewed.
      Between January and July 2013, we identified 61 patients who had unplanned breaks
      during treatment. We analyzed the social, emotional, educational, economic, and
      therapeutic barriers that led to nonadherence. RESULTS: Of the 61 patients who
      had unplanned breaks during treatment, 54% were males and 46% were females. Fifty
      seven percent of patients had head and neck cancers and 25% had gynecological
      cancers. Seventy-one percent of patients were planned for concurrent
      chemoradiation. The number of days of unplanned treatment breaks ranged from 3 to
      27 days. Social and therapeutic barriers were found to be the most common factor
      that led to nonadherence in these patients. CONCLUSION: Identification of
      barriers that lead to nonadherence, designing strategies to overcome such
      barriers and effective communication becomes imperative to ensure uninterrupted
      treatment. Based on the above analysis, we have designed several strategies to
      improve adherence to treatment among our patients.

PMID- 29469079
TI  - Impact of pictorial warning labels on tobacco products among patients attending
      outpatient department of a dental college in Bangalore city: A cross-sectional
      study.
AB  - AIM: The aim of this study is to assess the knowledge, attitude, and impact of
      pictorial warnings present on tobacco packets among patients attending outpatient
      department of a dental college of Bangalore city. MATERIALS AND METHODS: A cross
      sectional study was conducted among 419 patients through convenience sampling,
      using a structured close-ended questionnaire containing 35 questions. The
      participants were approached and invited to participate voluntarily. The data
      obtained were analyzed using descriptive statistics, Chi-square test and ANOVA.
      RESULTS: Mean age of the participants was 28.1 +/- 7.06 years. Out of total 419
      participants, 62.8% were tobacco users. About 40.6% of the participants had
      average knowledge and only 22.9% had positive attitude regarding the pictorial
      warnings. Nearly 77.9% of tobacco users had previously attempted decreased
      frequency of tobacco use and 63.7% had tried quitting the habit. The difference
      was statistically significant (P < 0.05 Chi-square test and ANOVA). CONCLUSION:
      The present study revealed that most of study participants have noticed the
      warnings on tobacco products, and most of them believe that they could understand
      warning labels. This study also showed that most of study participants believed
      that pictorial health warnings create awareness about probable health hazards of
      tobacco use and that these pictorial presentations on tobacco packs positively
      assist in reducing or quitting tobacco smoking.

PMID- 29469080
TI  - Role change as breadwinner in cancer caregiving.
AB  - INTRODUCTION: : Indian families are known for adopting the role of caregiver
      naturally when someone in the family falls ill to cancer. Although there were
      strong family structure and system existed here, now the changing family pattern
      and structure are challenging the role of cancer caregiving as well. OBJECTIVE: :
      This study analyses the life situation of caregivers of cancer survivors during
      the course of treatment and attempts to explore the areas of interventions for
      caregivers themselves. METHODS: : A descriptive research design was adopted for
      the study. A sample of 40 respondents was chosen for the study through purposive
      sampling technique. RESULTS: : Majority of the caregivers were females (75%) and
      fell into the age group of 35 to 45 years (65%). The education among the
      caregivers was varying between illiteracy to postgraduation. Majority of 95% of
      them adapted the dual role voluntarily and 85% of them felt that they were
      finding it very difficult to cope with the dual responsibility. About 60% of them
      felt that they would fail in their roles and were not satisfied with their
      performances dually. CONCLUSION: : Adaptation to a dual role involves time factor
      and as part of care to the caregiver, a guided interaction and orientation
      towards managing these roles would help them better ways to adapt. Given the
      scarcity of support system on Indian settings, the caregivers who do dual role
      have huge responsibility and challenges to deliver quality caregiving and fulfill
      their other roles as well. It is the duty of the complete health care system to
      seriously take this into consideration and to act on it.

PMID- 29469081
TI  - Statins and risk of cancer: A meta-analysis of randomized, double-blind, placebo
      controlled trials.
AB  - PURPOSE: Several meta-analyses of randomized controlled trials (RCTs) reported no
      association between the use of statins and the risk of cancer. However, they
      included open-label RCTs, which did not use placebo as a control group. This
      study aimed to evaluate the effect of statins on cancer risk using a meta
      analysis of randomized, double-blind, placebo-controlled trials (RDBPCTs).
      METHODS: We searched PubMed, EMBASE, and the Cochrane Library in March 2016. Two
      individual authors reviewed and selected RDBPCTs based on selection criteria.
      RESULTS: Out of 676 retrieved articles, a total of 21 RDBPCTs with 65,196
      participants (32,618 in the statin group and 32,578 in the placebo group) were
      included in the meta-analysis. Overall, we found that there was no significant
      association between the use of statins and the risk of cancer (relative risk
      0.97, 95% confidence interval 0.92-1.02, I2 = 0.0%) in a fixed-effect meta
      analysis. In addition, in the subgroup meta-analyses, no beneficial effect of
      statins was observed when analyzed by statin type, country, follow-up period,
      methodological quality, underlying diseases/population, and type of cancer.
      CONCLUSIONS: The current meta-analysis of RDBPCTs found that there was no
      association between the use of statins and the risk of cancer.

PMID- 29469082
TI  - Novel use of bioelectric impedence technique to detect alterations in body
      composition in advanced small cell lung cancer.
AB  - BACKGROUND: Malnutrition is frequent in lung cancer and is measured using various
      tools, including the novel bioelectric impedance technique for measuring body
      composition. However, the validation of this technique for assessing body
      composition in advanced small cell lung cancer (SCLC) is untested. METHODS: Forty
      one treatment naive patients (all males) and an equal number of age- and sex
      matched controls were evaluated by anthropometric measurements of skinfold
      thicknesses and body composition parameters such as body fat%, fat mass, fat-free
      mass (FFM), and total body water (TBW). RESULTS: The mean (SD) age of the patient
      group was 55.7 (7.5) years, median pack-years was 20 (range, 0-80), and mean (SD)
      duration of symptoms was 152.6 (153.7) days. Median Karnofsky Performance Scale
      was 70 (range, 50-90). Majority of our patients (68.3%) were Stage IV followed by
      Stage III (31.7%). The percentage of patients with low, normal, and high body
      mass index (BMI) was 31.7%, 61%, and 7.3%, respectively. All components of body
      composition, i.e., body fat%, FFM, and TBW were significantly lower in patients
      compared to controls. However, the body composition in patients and controls with
      normal BMI was similar. The phenomenon of sarcopenia as a cause of cancer
      cachexia may explain these findings, whereas the combination of loss of body fat
      and lean body mass may lead to weight loss and reduced BMI. CONCLUSION: Our
      results indicate that body composition is markedly altered in Indian patients
      with advanced SCLC. The impact of these parameters on clinically relevant
      outcomes needs further evaluation.

PMID- 29469083
TI  - Knowledge, attitude, and practice toward cervical cancer among women attending
      Obstetrics and Gynecology Department: A cross-sectional, hospital-based survey in
      South India.
AB  - INTRODUCTION: Cervical cancer-related deaths among women in India are often due
      to late diagnosis of disease. Knowledge about disease and early screening is the
      most effective measure for cervical cancer prevention. Lack of awareness,
      negative attitude, and poor practice about cervical cancer and screening are the
      major causes to increase the incidence of disease. AIM: The study is designed to
      assess knowledge, attitude, and practice (KAP) toward cervical cancer, screening,
      and prevention. SETTINGS AND DESIGN: A cross-sectional, hospital-based survey was
      conducted in women attending Obstetrics and Gynecology Department of a secondary
      care referral hospital. MATERIALS AND METHODS: A total of 403 subjects were
      enrolled and subjected for interview using prevalidated KAP questionnaire on
      cervical cancer. STATISTICAL ANALYSIS: Descriptive statistics were used to
      represent the sociodemographic characteristics and KAP levels. Association of
      sociodemographic variables with KAP levels is determined using Chi-square test.
      RESULTS AND DISCUSSION: Most of (301; 74.6%) the respondents had heard about
      cervical cancer and majority of them are heard from media (168; 41.6%) and
      friends (83; 20.5%). Most women knew symptoms (259; 64.2%), risk factors (253;
      62.7%), screening methods (310; 76.9%), and preventive measures (249; 61.7%) for
      cervical cancer. More than half of the women (252; 62.5%) having positive
      attitude toward screening. More than three-fourth of women (349; 86.6%) are not
      having practice toward cervical cancer screening. Sociodemographic
      characteristics are strongly associated with KAP levels. CONCLUSION: Although
      women are having good knowledge, positive attitude toward cervical cancer
      screening and prevention still there is a gap to transform it into practice.
      There is a need for more educational programs to connect identified knowledge
      slits and uplift of regular practice of cervical cancer screening.

PMID- 29469084
TI  - Summer school in oncology - setting a benchmark in inspiring the future
      oncologists - a surgical postgraduate's perspective.

PMID- 29469085
TI  - Autobiography of a bosom.

PMID- 29469086
TI  - Retraction: Histopathological analysis of meningioma and its variants: A study of
      fifty cases.
AB  - [This corrects the article DOI: 10.4103/ijc.IJC_119_17.].

PMID- 29469088
TI  - Authors' reply: Paraneoplastic autoimmune multi-organ syndrome is a distinct
      entity from traditional pemphigus subtypes.

PMID- 29469087
TI  - Downregulation of HIF-2alpha Reverse the Chemotherapy Resistance of Lung
      Adenocarcinoma A549 Cells to Cisplatin.
AB  - BACKGROUND Cisplatin (DDP)-based systemic chemotherapy has been widely used in
      the treatment of postoperative or advanced NSCLC patients, however, its effective
      rate is only 14~40%. HIF-2alpha can upregulate drug-resistant-related genes
      expression and lead to chemotherapy resistance in many tumors. However, little is
      known about the relationship between HIF-2alpha and chemotherapy resistance of
      lung cancer cells. MATERIAL AND METHODS In our study, the siRNA expression
      vectors targeting the HIF-2alpha gene were designed, constructed, and transfected
      into A549 cells. MTT assay and western blot analysis of P-glycoprotein 1 (P-gp)
      were used to explore the transfer influence of HIF-2alpha gene silencing on the
      A549 cells in the cisplatin-based chemotherapy resistance. RESULTS After
      transfection with the siRNAHIF-2alpha into A549 cells, mRNA and protein
      expression of HIF-2alpha were downregulated. At the same time, expression of P-gp
      decreased significantly. Furthermore, the sensitivity to cisplatin significantly
      increased. CONCLUSIONS The constructed siRNA expression vectors can effectively
      suppress the expression of HIF-2alpha and P-gp, which then can reverse the
      chemotherapy resistance of A549 cells.

PMID- 29469089
TI  - Paraneoplastic autoimmune multi-organ syndrome is a distinct entity from
      traditional pemphigus subtypes.

PMID- 29469090
TI  - Sterically controlled mechanochemistry under hydrostatic pressure.
AB  - Mechanical stimuli can modify the energy landscape of chemical reactions and
      enable reaction pathways, offering a synthetic strategy that complements
      conventional chemistry. These mechanochemical mechanisms have been studied
      extensively in one-dimensional polymers under tensile stress using ring-opening
      and reorganization, polymer unzipping and disulfide reduction as model reactions.
      In these systems, the pulling force stretches chemical bonds, initiating the
      reaction. Additionally, it has been shown that forces orthogonal to the chemical
      bonds can alter the rate of bond dissociation. However, these bond activation
      mechanisms have not been possible under isotropic, compressive stress (that is,
      hydrostatic pressure). Here we show that mechanochemistry through isotropic
      compression is possible by molecularly engineering structures that can translate
      macroscopic isotropic stress into molecular-level anisotropic strain. We engineer
      molecules with mechanically heterogeneous components-a compressible ('soft')
      mechanophore and incompressible ('hard') ligands. In these 'molecular anvils',
      isotropic stress leads to relative motions of the rigid ligands, anisotropically
      deforming the compressible mechanophore and activating bonds. Conversely, rigid
      ligands in steric contact impede relative motion, blocking reactivity. We combine
      experiments and computations to demonstrate hydrostatic-pressure-driven redox
      reactions in metal-organic chalcogenides that incorporate molecular elements that
      have heterogeneous compressibility, in which bending of bond angles or shearing
      of adjacent chains activates the metal-chalcogen bonds, leading to the formation
      of the elemental metal. These results reveal an unexplored reaction mechanism and
      suggest possible strategies for high-specificity mechanosynthesis.

PMID- 29469091
TI  - Crowther et al. reply.

PMID- 29469092
TI  - Structure and mechanogating mechanism of the Piezo1 channel.
AB  - The mechanosensitive Piezo channels function as key eukaryotic
      mechanotransducers. However, their structures and mechanogating mechanisms remain
      unknown. Here we determine the three-bladed, propeller-like electron cryo
      microscopy structure of mouse Piezo1 and functionally reveal its
      mechanotransduction components. Despite the lack of sequence repetition, we
      identify nine repetitive units consisting of four transmembrane helices each
      which we term transmembrane helical units (THUs)-which assemble into a highly
      curved blade-like structure. The last transmembrane helix encloses a hydrophobic
      pore, followed by three intracellular fenestration sites and side portals that
      contain pore-property-determining residues. The central region forms a 90 A-long
      intracellular beam-like structure, which undergoes a lever-like motion to connect
      THUs to the pore via the interfaces of the C-terminal domain, the anchor
      resembling domain and the outer helix. Deleting extracellular loops in the distal
      THUs or mutating single residues in the beam impairs the mechanical activation of
      Piezo1. Overall, Piezo1 possesses a unique 38-transmembrane-helix topology and
      designated mechanotransduction components, which enable a lever-like
      mechanogating mechanism.

PMID- 29469093
TI  - Multi-terminal memtransistors from polycrystalline monolayer molybdenum
      disulfide.
AB  - Memristors are two-terminal passive circuit elements that have been developed for
      use in non-volatile resistive random-access memory and may also be useful in
      neuromorphic computing. Memristors have higher endurance and faster read/write
      times than flash memory and can provide multi-bit data storage. However, although
      two-terminal memristors have demonstrated capacity for basic neural functions,
      synapses in the human brain outnumber neurons by more than a thousandfold, which
      implies that multi-terminal memristors are needed to perform complex functions
      such as heterosynaptic plasticity. Previous attempts to move beyond two-terminal
      memristors, such as the three-terminal Widrow-Hoff memristor and field-effect
      transistors with nanoionic gates or floating gates, did not achieve memristive
      switching in the transistor. Here we report the experimental realization of a
      multi-terminal hybrid memristor and transistor (that is, a memtransistor) using
      polycrystalline monolayer molybdenum disulfide (MoS2) in a scalable fabrication
      process. The two-dimensional MoS2 memtransistors show gate tunability in
      individual resistance states by four orders of magnitude, as well as large
      switching ratios, high cycling endurance and long-term retention of states. In
      addition to conventional neural learning behaviour of long-term
      potentiation/depression, six-terminal MoS2 memtransistors have gate-tunable
      heterosynaptic functionality, which is not achievable using two-terminal
      memristors. For example, the conductance between a pair of floating electrodes
      (pre- and post-synaptic neurons) is varied by a factor of about ten by applying
      voltage pulses to modulatory terminals. In situ scanning probe microscopy,
      cryogenic charge transport measurements and device modelling reveal that the bias
      induced motion of MoS2 defects drives resistive switching by dynamically varying
      Schottky barrier heights. Overall, the seamless integration of a memristor and
      transistor into one multi-terminal device could enable complex neuromorphic
      learning and the study of the physics of defect kinetics in two-dimensional
      materials.

PMID- 29469094
TI  - Importance of investing in adolescence from a developmental science perspective.
AB  - This review summarizes the case for investing in adolescence as a period of rapid
      growth, learning, adaptation, and formational neurobiological development.
      Adolescence is a dynamic maturational period during which young lives can pivot
      rapidly-in both negative and positive directions. Scientific progress in
      understanding adolescent development provides actionable insights into windows of
      opportunity during which policies can have a positive impact on developmental
      trajectories relating to health, education, and social and economic success.
      Given current global changes and challenges that affect adolescents, there is a
      compelling need to leverage these advances in developmental science to inform
      strategic investments in adolescent health.

PMID- 29469096
TI  - Palladium-catalysed electrophilic aromatic C-H fluorination.
AB  - Aryl fluorides are widely used in the pharmaceutical and agrochemical industries,
      and recent advances have enabled their synthesis through the conversion of
      various functional groups. However, there is a lack of general methods for direct
      aromatic carbon-hydrogen (C-H) fluorination. Conventional methods require the use
      of either strong fluorinating reagents, which are often unselective and difficult
      to handle, such as elemental fluorine, or less reactive reagents that attack only
      the most activated arenes, which reduces the substrate scope. A method for the
      direct fluorination of aromatic C-H bonds could facilitate access to fluorinated
      derivatives of functional molecules that would otherwise be difficult to produce.
      For example, drug candidates with improved properties, such as increased
      metabolic stability or better blood-brain-barrier penetration, may become
      available. Here we describe an approach to catalysis and the resulting
      development of an undirected, palladium-catalysed method for aromatic C-H
      fluorination using mild electrophilic fluorinating reagents. The reaction
      involves a mode of catalysis that is unusual in aromatic C-H functionalization
      because no organometallic intermediate is formed; instead, a reactive transition
      metal-fluoride electrophile is generated catalytically for the fluorination of
      arenes that do not otherwise react with mild fluorinating reagents. The scope and
      functional-group tolerance of this reaction could provide access to functional
      fluorinated molecules in pharmaceutical and agrochemical development that would
      otherwise not be readily accessible.

PMID- 29469097
TI  - A surge of light at the birth of a supernova.
AB  - It is difficult to establish the properties of massive stars that explode as
      supernovae. The electromagnetic emission during the first minutes to hours after
      the emergence of the shock from the stellar surface conveys important information
      about the final evolution and structure of the exploding star. However, the
      unpredictable nature of supernova events hinders the detection of this brief
      initial phase. Here we report the serendipitous discovery of a newly born, normal
      type IIb supernova (SN 2016gkg), which reveals a rapid brightening at optical
      wavelengths of about 40 magnitudes per day. The very frequent sampling of the
      observations allowed us to study in detail the outermost structure of the
      progenitor of the supernova and the physics of the emergence of the shock. We
      develop hydrodynamical models of the explosion that naturally account for the
      complete evolution of the supernova over distinct phases regulated by different
      physical processes. This result suggests that it is appropriate to decouple the
      treatment of the shock propagation from the unknown mechanism that triggers the
      explosion.

PMID- 29469098
TI  - Predicting soil carbon loss with warming.

PMID- 29469095
TI  - Adolescence and the next generation.
AB  - Adolescent growth and social development shape the early development of offspring
      from preconception through to the post-partum period through distinct processes
      in males and females. At a time of great change in the forces shaping
      adolescence, including the timing of parenthood, investments in today's
      adolescents, the largest cohort in human history, will yield great dividends for
      future generations.

PMID- 29469101
TI  - Correction.

PMID- 29469102
TI  - Adolescence research must grow up.

PMID- 29469099
TI  - Dynamics of body time, social time and life history at adolescence.
AB  - Recent opposing trends towards earlier physical maturation and later social
      maturation present a conundrum of apparent biological-social mismatch. Here we
      use life history analysis from evolutionary ecology to identify forces that drive
      these shifts. Together with findings in developmental science, our life history
      analysis indicates that adolescence is a distinctive period for biological
      embedding of culture. Ethnographic evidence shows that mass education is a novel
      feature of the globalizing cultural configurations of adolescence, which are
      driven by transformations in labour, livelihood and lifestyle. Evaluation of the
      life history trade-offs and sociocultural ecologies that are experienced by
      adolescents may offer a practical basis for enhancing their development.

PMID- 29469104
TI  - Race- and gender-based bias persists in US science.

PMID- 29469105
TI  - Solar geoengineering must take temperature debt into account.

PMID- 29469106
TI  - Correction.

PMID- 29469107
TI  - Deep learning for biology.

PMID- 29469108
TI  - Smartphones are bad for some teens, not all.

PMID- 29469109
TI  - As a Saudi woman scientist, I'm tired of negative stereotypes.

PMID- 29469110
TI  - CRISPR hack transform s cells into data recorders.

PMID- 29469111
TI  - Correction.

PMID- 29469112
TI  - Sex and drugs and self-control: how the teen brain navigates risk.

PMID- 29469113
TI  - Neurons mimicked by electronics.

PMID- 29469114
TI  - Coming of age.

PMID- 29469116
TI  - Teen spirit in the lab.

PMID- 29469117
TI  - Understand the lives of youth in low-income countries.

PMID- 29469118
TI  - Science needs to redefine excellence.

PMID- 29469119
TI  - Italian election leaves science out in the cold.

PMID- 29469122
TI  - Physicists plan antimatter's first outing - in a van.

PMID- 29469120
TI  - Indonesian scientists hamstrung by year-long funding delay.

PMID- 29469123
TI  - Use imprint of society and history on climate data to inform climate services.

PMID- 29469125
TI  - Pruning hypothesis comes of age.

PMID- 29469126
TI  - Root systems offer insight into better soils.

PMID- 29469127
TI  - Who exactly counts as an adolescent?

PMID- 29469128
TI  - Molecules pressured to react.

PMID- 29469129
TI  - Authorship position should not serve as a proxy metric.

PMID- 29469130
TI  - An inflammatory transcriptional switch.

PMID- 29469131
TI  - Ocean-wide sensor array provides new look at global ocean current.

PMID- 29469132
TI  - Orangutan losses, brain-injury test and Grace Mugabe's PhD.

PMID- 29469133
TI  - Why current negative-emissions strategies remain 'magical thinking'.

PMID- 29469134
TI  - Force-activated ion channels in close-up.

PMID- 29469135
TI  - How to make replication the norm.

PMID- 29469136
TI  - Acute lymphoblastic leukemia in a child with Leri-Weill syndrome and complete
      SHOX gene deletion: A Case Report.
AB  - BACKGROUND: Leri-Weill syndrome (LWS) ranks among conditions with short stature
      homeobox gene (SHOX) haploinsufficiency. Data on possible association of SHOX
      aberrations with malignant diseases are scarce. METHODS AND RESULTS: We report a
      unique case of an 8-year-old girl who was successfully treated for acute
      lymphoblastic leukemia (pre-B ALL, intermediate risk) and was subsequently
      diagnosed with LWS due to characteristic clinical appearance (short
      disproportionate stature, Madelung deformity of the wrist) and molecular genetic
      examination (complete deletion of SHOX). An identical SHOX deletion was
      identified also in the patient's mother. Leukemic cells of the patient were
      retrospectively examined by array comparative genomic hybridization (aCGH), which
      revealed five regions of deletions at chromosome X, including the SHOX gene
      locus. CONCLUSION: Growth retardation in children with hemato-oncologic
      malignancies cannot always be attributed to cytotoxic treatment and should be
      carefully evaluated, especially with regards to growth hormone therapy.

PMID- 29469137
TI  - Impact of food structure on the compatibility of heated WPI-pectin-complexes in
      meat dispersions.
AB  - Process-stable complexes composed of whey protein isolate (WPI) and sugar beet
      pectin have great potential as structuring agents or fat replacers in foods. The
      current study investigates the compatibility of heated WPI : pectin complexes in
      different meat matrices. Spreadable raw-fermented sausages and sliceable emulsion
      type sausages were therefore manufactured containing biopolymer complexes with
      various WPI : pectin ratios r (2 : 1, 8 : 1). Macro- and microstructural
      properties of the meat dispersions were analyzed in terms of colour, texture,
      rheometry, sensory, and confocal laser scanning microscopy (CLSM) measurements.
      Textural and sensorial results demonstrated that the meat products became
      increasingly soft and yellowish as the biopolymer ratio r was increased
      regardless of the meat matrix, whereas pH and water activity values were not
      affected. CLSM images revealed that the meat protein network became disrupted and
      loose in the presence of pectin, which was attributed to a thermodynamic
      incompatibility effect. The results obtained from this study highlight that
      biopolymer complexes might be suitable fat mimetics, particularly for spreadable
      meat products.

PMID- 29469138
TI  - X-ray transparent microfluidic platforms for membrane protein crystallization
      with microseeds.
AB  - Crystallization of membrane proteins is a critical step for uncovering atomic
      resolution 3-D structures and elucidating structure-function relationships.
      Microseeding, the process of transferring sub-microscopic crystal nuclei from
      initial screens into new crystallization experiments, is an effective, yet
      underutilized approach to grow crystals suitable for X-ray crystallography. Here,
      we report simplified methods for crystallization of membrane proteins that
      utilize microseeding in X-ray transparent microfluidic chips. First, a
      microfluidic method for introduction of microseed dilutions into metastable
      crystallization experiments is demonstrated for photoactive yellow protein and
      cytochrome bo3 oxidase. As microseed concentration decreased, the number of
      crystals decreased while the average size increased. Second, we demonstrate a
      microfluidic chip for microseed screening, where many crystallization conditions
      were formulated on-chip prior to mixing with microseeds. Crystallization
      composition, crystal size, and diffraction data were collected and mapped on
      phase diagrams, which revealed that crystals of similar diffraction quality and
      size typically grow in distinct regions of the phase diagram.

PMID- 29469140
TI  - Gold nanoparticles supported on mesoporous iron oxide for enhanced CO oxidation
      reaction.
AB  - Herein, we report the synthesis of gold (Au)-loaded mesoporous iron oxide (Fe2O3)
      as a catalyst for both CO and NH3 oxidation. The mesoporous Fe2O3 is firstly
      prepared using polymeric micelles made of an asymmetric triblock copolymer
      poly(styrene-b-acrylic acid-b-ethylene glycol) (PS-b-PAA-b-PEG). Owing to its
      unique porous structure and large surface area (87.0 m2 g-1), the as-prepared
      mesoporous Fe2O3 can be loaded with a considerably higher amount of Au
      nanoparticles (Au NPs) (7.9 wt%) compared to the commercial Fe2O3 powder (0.8
      wt%). Following the Au loading, the mesoporous Fe2O3 structure is still well
      retained and Au NPs with varying sizes of 3-10 nm are dispersed throughout the
      mesoporous support. When evaluated for CO oxidation, the Au-loaded mesoporous
      Fe2O3 catalyst shows up to 20% higher CO conversion efficiency compared to the
      commercial Au/Fe2O3 catalyst, especially at lower temperatures (25-150  degrees
      C), suggesting the promising potential of this catalyst for low-temperature CO
      oxidation. Furthermore, the Au-loaded mesoporous Fe2O3 catalyst also displays a
      higher catalytic activity for NH3 oxidation with a respectable conversion
      efficiency of 37.4% compared to the commercial Au/Fe2O3 catalyst (15.6%) at 200 
      degrees C. The significant enhancement in the catalytic performance of the Au
      loaded mesoporous Fe2O3 catalyst for both CO and NH3 oxidation may be attributed
      to the improved dispersion of the Au NPs and enhanced diffusivity of the reactant
      molecules due to the presence of mesopores and a higher oxygen activation rate
      contributed by the increased number of active sites, respectively.

PMID- 29469139
TI  - Entropic trap purification of long DNA.
AB  - Long-read genomic applications, such as genome mapping in nanochannels, require
      long DNA that is free of small-DNA impurities. We have developed a chip-based
      system based on entropic trapping that can simultaneously concentrate and purify
      a long DNA sample under the alternating application of an applied pressure (for
      sample injection) and an electric field (for filtration and concentration). In
      contrast, short DNA tends to pass through the filter owing to its comparatively
      weak entropic penalty for entering the nanoslit. The single-stage prototype
      developed here, which operates in a continuous pulsatile manner, achieves
      selectivities of up to 3.5 for lambda-phage DNA (48.5 kilobase pairs) compared to
      a 2 kilobase pair standard based on experimental data for the fraction filtered
      using pure samples of each species. The device is fabricated in fused silica
      using standard clean-room methods, making it compatible for integration with long
      read genomics technologies.

PMID- 29469141
TI  - Renaissance of pyridine-oxazolines as chiral ligands for asymmetric catalysis.
AB  - Oxazoline-containing ligands have been widely employed in numerous asymmetric
      catalytic reactions. Pyridine-oxazoline-type ligands, a class of hybrid ligands,
      were designed earlier than bisoxazoline and phosphine-oxazoline ligands; however,
      their unique properties have only been discovered recently. Pyridine-oxazoline
      type chiral ligands are rapidly becoming popular for use in asymmetric catalysis,
      especially for several new and efficient asymmetric methodologies. Several types
      of challenging asymmetric reactions have been discovered recently using pyridine
      oxazoline-type ligands showing their special properties and potential for future
      application in a wide range of new catalytic methodologies. This review provides
      an overview of this field, with the aim of highlighting both ligand design and
      synthetic methodology development.

PMID- 29469143
TI  - A little key to oxalate formation in oil paints: protective patina or chemical
      reactor?
AB  - By means of synchrotron based techniques, we propose an integrated mechanism for
      the degradation of 19th century chrome yellow oil paints based on pigment
      reconstructions from historical recipes. We show that for certain paint
      formulations the darkening of these colours is triggered by the binder
      photodegradation which leads to the formation of calcium oxalate at the expense
      of the filler CaCO3, and the reduction of the chrome yellow pigment (Cr6+/Cr3+).
      Considering that calcium oxalate is formed as a thin superficial layer, that may
      prevent light absorption by the paint bulk, we discuss its role as protective
      patina.

PMID- 29469144
TI  - Identification of a novel ligand for the ATAD2 bromodomain with selectivity over
      BRD4 through a fragment growing approach.
AB  - ATAD2 is an ATPase that is overexpressed in a variety of cancers and associated
      with a poor patient prognosis. This protein has been suggested to function as a
      cofactor for a range of transcription factors, including the proto-oncogene MYC
      and the androgen receptor. ATAD2 comprises an ATPase domain, implicated in
      chromatin remodelling, and a bromodomain which allows it to interact with
      acetylated histone tails. Dissection of the functional roles of these two domains
      would benefit from the availability of selective, cell-permeable pharmacological
      probes. An in silico evaluation of the 3D structures of various bromodomains
      suggested that developing small molecule ligands for the bromodomain of ATAD2 is
      likely to be challenging, although recent reports have shown that ATAD2
      bromodomain ligands can be identified. We report a structure-guided fragment
      based approach to identify lead compounds for ATAD2 bromodomain inhibitor
      development. Our findings indicate that the ATAD2 bromodomain can accommodate
      fragment hits (Mr < 200) that yield productive structure-activity relationships,
      and structure-guided design enabled the introduction of selectivity over BRD4.

PMID- 29469145
TI  - Conductive 3D sponges for affordable and highly-efficient water purification.
AB  - Effective, affordable and low energy water purification technologies are highly
      desirable to address the current environmental issues. In this study, we
      developed a low-cost method to achieve efficient organic pollutants degradation
      by incorporating conductive nanomaterials (i.e., carbon nanotubes, CNTs) to
      assist electro-oxidation, leading to an efficient conductive nano-sponge
      filtration device. The integration of electrochemistry has significantly improved
      the performance of the sponge-based device to adsorb and oxidize organic
      compounds in aqueous solution. In particular, CNT materials could serve as both
      high-performance electro-catalysts for pollutant degradation and conductive
      additives that make polyurethane sponges highly conductive. On the other hand,
      the polyurethane sponge could work as a low-cost and highly porous matrix that
      could effectively host these CNT conductors. The conductive sponge can be easily
      fabricated by a simple dying based approach. The as-fabricated gravity fed device
      could effectively oxidize two model organic compounds (i.e., >92% antibiotic
      tetracycline and >94% methyl orange) via a single pass through the conductive
      sponge under the optimized experimental conditions (e.g., [Na2SO4] = 10 mmol L-1,
      [CNT] = 0.3 mg mL-1, and [SDBS] = 2.0 mg mL-1). We have achieved >88% degradation
      efficiency for the antibiotic tetracycline within 6 h of continuous operation
      with an average electro-oxidation flux of 0.82 +/- 0.05 mol h-1 m-2 and an energy
      requirement of 1.0 kW h kg-1 COD or <0.02 kW h m-3. These promising data make our
      CNT-sponge filtration device attractive for affordable and effective water
      purification.

PMID- 29469146
TI  - Nanocomposites based on hierarchical porous carbon fiber@vanadium nitride
      nanoparticles as supercapacitor electrodes.
AB  - In this study, a hybrid electrode material for supercapacitors based on
      hierarchical porous carbon fiber@vanadium nitride nanoparticles is fabricated
      using the method of phase-separation mediated by the PAA-b-PAN-b-PAA tri-block
      copolymer. In the phase-separation procedure, the ionic block copolymer self
      assembled on the surface of carbon nanofibers, and is used to adsorb NH4VO3.
      Thermal treatment at controlled temperatures under an NH3 : N2 atmosphere led to
      the formation of vanadium nitride nanoparticles that are distributed uniformly on
      the nanofiber surface. By changing the PAN to PAA-b-PAN-b-PAA ratio in the
      casting solution, a maximum specific capacitance of 240.5 F g-1 is achieved at
      the current density of 0.5 A g-1 with good rate capability at a capacitance
      retention of 72.1% at 5.0 A g-1 in an aqueous electrolyte of 6 mol L-1 KOH within
      the potential range of -1.10 to 0 V (rN/A = 1.5/1.0). Moreover, an asymmetric
      supercapacitor is assembled by using the hierarchical porous carbon
      fiber@vanadium nitride as the negative electrode and Ni(OH)2 as the positive
      electrode. Remarkably, at the power density of 400 W kg-1, the supercapacitor
      device delivers a better energy density of 39.3 W h kg-1. It also shows excellent
      electrochemical stability, and thus might be used as a promising energy-storage
      device.

PMID- 29469147
TI  - Rhodium-catalyzed C-H bond activation alkylation and cyclization of 2
      arylquinazolin-4-ones.
AB  - An efficient method for the synthesis of isoquinolino[1,2-b]quinazolin-8-one
      derivatives and 12-methyl-12H-isoindolo[1,2-b]quinazoline-10-one derivatives is
      described herein. With rhodium catalysis, the desired products are obtained
      through a sequence reaction of C-H activation-based alkenylation and
      intramolecular aza-Heck-type cyclization. The developed method has a wide range
      of substrate tolerance under mild conditions and provides an alternative for the
      structural elaboration of quinazoline compounds.

PMID- 29469148
TI  - Advances in point-of-care diagnostic devices in cancers.
AB  - The early diagnosis and monitoring of the progress of cancers are limited due to
      the lack of adequate screening tools. Ultrasensitive and precise point-of-care
      cancer diagnostic tools are required for the early detection and screening of
      cancer biomarkers at the bedside with accuracy and specificity of diagnosis.
      Recent advances in nano- and microfabrication based technologies integrated with
      different sensing platforms are accelerating the development of rapid, low-cost
      and reliable point-of-care cancer diagnostic devices. These technologies allow
      low volumes of reagents and samples, reduced analysis time, are disposable and
      portable, and provide ultrasensitive multiplexed analysis to improve diagnostic
      and prognostic evaluations. Networking for communicating and transferring the
      results through wireless networks provides additional opportunities for remote
      telemedicine-based diagnosis and planning of treatment regimens, even in semi
      urban and rural areas. This review focuses on recent advances in point-of-care
      cancer diagnostics for efficient treatment along with the key challenges,
      opportunities and future scope of these technologies for clinical translation.

PMID- 29469149
TI  - Technical aspects of nicking enzyme assisted amplification.
AB  - Nicking enzyme assisted amplification (NEAA) is an extremely rapid method for
      molecular diagnosis. However, this technology is not widely applied for real
      sample analysis because the overproduced non-specific products limit its
      sensitivity and raise the threshold of detection methods. Here, we have found
      that the non-specific amplification is mainly caused by the coexistence of Bst
      polymerase, nicking primers and dNTP. The highly active nicking enzyme directs
      and accelerates the non-specific amplification in a way which favors nicking. To
      suppress the non-specific amplification, the nicking enzyme concentration,
      reaction temperature, and magnesium ion concentration are optimized. The
      compatibility of Bst polymerase with the concentration of the monovalent cation
      is also crucial. Besides, the sensitivity could be enhanced by shortening the
      target sequences and priming the 3' end of the target.

PMID- 29469155
TI  - Alkane guest packing drives switching between multimeric deep-cavity cavitand
      assembly states.
AB  - Alkane guest transfer into aqueous dimeric, tetrameric, hexameric, and octameric
      assemblies of the deep-cavity cavitand TEMOA is examined using molecular
      simulations. The experimental transitions between aggregation states strongly
      correlate with calculated alkane transfer free energy minima, demonstrating the
      guiding role of guest packing on stabilizing multimeric complexes. The predictive
      simulation approach described affords a salient rationale as to why octameric
      assemblies have yet to be experimentally observed.

PMID- 29469156
TI  - Red fluorescent probes for real-time imaging of the cell cycle by dynamic
      monitoring of the nucleolus and chromosome.
AB  - Two cationic molecular rotors, 1 and 2, capable of real-time cell-cycle imaging
      by specifically dynamic monitoring of nucleolus and chromosome changes were
      developed. A further study shows that fluorescence enhancements in the nucleolus
      and chromosome are attributed to a combination effect of interaction with nucleic
      acid and high condensation of the nucleolus and chromosome.

PMID- 29469158
TI  - A novel potentiometric immunoassay for carcinoma antigen 15-3 by coupling
      enzymatic biocatalytic precipitation with a nanogold labelling strategy.
AB  - Methods based on potentiometric measurement have been developed for immunoassays,
      but most exhibit low sensitivities and are unsuitable for early diagnosis of
      disease. Herein we design a new potentiometric immunosensing platform for the
      sensitive detection of carcinoma antigen 15-3 (CA 15-3) by coupling with
      enzymatic biocatalytic precipitation and a nanogold labeling technique. The
      sandwich-type immunoreaction is carried out on a monoclonal anti-CA 15-3 capture
      antibody-modified working electrode, using horseradish peroxidase (HRP) and
      polyclonal anti-CA 15-3 detection antibody-labeled gold nanoparticles. Upon the
      introduction of target CA 15-3, the carried HRP molecules with an immunocomplex
      catalyze the oxidation of 4-chloro-1-naphthol (4-CN) into the insoluble benzo-4
      chlorohexadienone. The formed product coated on the surface of the modified
      electrode results in a change of the electrical potential. Under optimal
      conditions, the shift in the electrical potential relative to the background
      signal increases with the increasing target CA 15-3 concentration, and exhibits a
      good linear relationship within the dynamic range of 0.01-30 U mL-1 at a
      detection limit of 7.8 mU mL-1. Good precision and reproducibility, and high
      specificity were acquired for the analysis of 15 human serum specimens, giving
      well matched results with those obtained from a human CA 15-3 ELISA kit.

PMID- 29469160
TI  - trans to cis photo-isomerization in merocyanine dysprosium and yttrium complexes.
AB  - We report the synthesis of two lanthanide complexes including a chelating
      merocyanine (MC) ligand obtained from the reaction of a bis(pyridinemethyl)amine
      substituted spiropyran with yttrium(iii) or dysprosium(iii) triflate salts, whose
      structures were confirmed both in the solid state and in solution by single
      crystal X-ray diffraction studies and NMR investigations. The obtained
      merocyanine metal complexes can reversibly undergo a photo-triggered
      transformation consisting of a partial isomerization of the trans-merocyanine
      ligand to its cis isomer (cis-MC) providing complexes in which the metal
      phenolate bond is retained. SQUID magnetometry experiments in combination with ab
      initio calculations were used to evidence and rationalize the single-molecule
      magnet behavior of the dysprosium complex and to probe the changes in the
      dysprosium ion local environment upon photo-isomerization.

PMID- 29469161
TI  - Electrochemical method for the quantitative determination of Escherichia coli
      based on gold functionalized FTO substrate.
AB  - This work presents a novel rapid and sensitive label-free electrochemical method
      for the detection of bacteria on surface nanostructures. A simple electrochemical
      deposition and calcination method is employed to prepare different gold
      nanostructures on FTO substrate. The sensor based on nanostructure gold exhibits
      excellent linear relation between E. coli DH5alpha bacteria and the changes of
      DeltaRct, especially FTO-GEDC-D30, with a correction coefficient R2 = 0.998. Both
      the spectrophotometric (OD600 methods) and fluorescence-staining methods also
      verified the reliability of electrochemical impedance spectroscopy (EIS) methods
      for evaluating the antibacterial activity of the gold nanostructure.

PMID- 29469162
TI  - Investigating enhanced thermoelectric performance of graphene-based nano
      structures.
AB  - Recently, it has been demonstrated that graphene nano-ribbons (GNRs) exhibit
      superior thermoelectric performance compared to graphene sheets. However, the
      underlying mechanism behind this enhancement has not been systematically
      investigated and significant opportunity remains for further enhancement of the
      thermoelectric performance of GNRs by optimizing their charge carrier
      concentration. In this work, we modulate the carrier concentration of graphene
      based nano-structures using a gate voltage and investigate the resulting carrier
      concentration-dependent thermoelectric parameters using the Boltzmann transport
      equations. We investigate the effect of energy dependent scattering time and the
      role of substrate-induced charge carrier fluctuation in optimizing the Seebeck
      coefficient and power factor. Our approach predicts the scattering mechanism and
      the extent of the charge carrier fluctuation in different samples and explains
      the enhancement of thermoelectric performance of GNR samples. Subsequently, we
      propose a route towards the enhancement of thermoelectric performance of graphene
      based devices which can also be applied to other two-dimensional materials.

PMID- 29469163
TI  - A method for characterising human intervertebral disc glycosaminoglycan
      disaccharides using liquid chromatography-mass spectrometry with multiple
      reaction monitoring.
AB  - Intervertebral disc (IVD) degeneration results in the depletion of proteoglycans
      and glycosaminoglycans (GAGs), which can lead to structural and mechanical loss
      of IVD function, ingrowth of nociceptive nerve fibres and eventually discogenic
      pain. Specific GAG types as well as their disaccharide patterns can be predictive
      of disease and degeneration in several tissues but have not been comprehensively
      studied within the IVD. A highly sensitive mass spectrometry based technique with
      multiple reaction monitoring (MRM) was used to provide characterisation of
      chondroitin sulphate (CS), hyaluronic acid (HA), heparan sulphate (HS) and their
      disaccharide sulphation patterns across different anatomical regions of human
      IVDs. Principal component analysis further distinguished important regional
      variations and proposed potential ageing variations in GAG profiles. CS was the
      GAG in greatest abundance in the IVD followed by HA and HS. Principal component
      analysis identified clear separation of GAG profiles between nucleus pulposus and
      annulus fibrosus in young and old specimens. Distinct patterns of predominantly
      expressed disaccharides of CS and HS between young and old IVD samples, provided
      preliminary evidence that important alterations in disaccharides occur within
      IVDs during ageing. This technique offered a novel approach to identify and
      quantify specific GAG disaccharides in human IVDs and the data presented were the
      first to offer insight into the spatial distribution as well as association with
      ageing of GAGs and GAG disaccharide sulphation patterns across the human IVD.

PMID- 29469164
TI  - Heart rate variability affected by radiofrequency electromagnetic field in
      adolescent students.
AB  - This study examines the possible effect of radiofrequency (RF) electromagnetic
      fields (EMF) on the autonomic nervous system (ANS). The effect of RF EMF on ANS
      activity was studied by measuring heart rate variability (HRV) during ortho
      clinostatic test (i.e., transition from lying to standing and back) in 46 healthy
      grammar school students. A 1788 MHz pulsed wave with intensity of 54 +/- 1.6 V/m
      was applied intermittently for 18 min in each trial. Maximum specific absorption
      rate (SAR10 ) value was determined to 0.405 W/kg. We also measured the
      respiration rate and estimated a subjective perception of EMF exposure. RF
      exposure decreased heart rate of subjects in a lying position, while no such
      change was seen in standing students. After exposure while lying, a rise in high
      frequency band of HRV and root Mean Square of the Successive Differences was
      observed, which indicated an increase in parasympathetic nerve activity. Tympanic
      temperature and skin temperature were measured showing no heating under RF
      exposure. No RF effect on respiration rate was observed. None of the tested
      subjects were able to distinguish real exposure from sham exposure when queried
      at the end of the trial. In conclusion, short-term RF EMF exposure of students in
      a lying position during the ortho-clinostatic test affected ANS with significant
      increase in parasympathetic nerve activity compared to sham exposed group.
      Bioelectromagnetics. 39:277-288, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29469165
TI  - Effect of exercise intensity on circulating microparticles in men and women.
AB  - NEW FINDINGS: What is the central question of this study? What is the effect of
      exercise intensity on circulating microparticle populations in young, healthy men
      and women? What is the main finding and its importance? Acute, moderate-intensity
      continuous exercise and high-intensity interval exercise altered distinct
      microparticle populations during and after exercise in addition to a sex-specific
      response in CD62E+ microparticles. The microparticles studied contribute to
      cardiovascular disease progression, regulate vascular function and facilitate new
      blood vessel formation. Thus, characterizing the impact of intensity on exercise
      induced microparticle responses advances our understanding of potential
      mechanisms underlying the beneficial vascular adaptations to exercise. ABSTRACT:
      Circulating microparticles (MPs) are biological vectors of information within the
      cardiovascular system that elicit both deleterious and beneficial effects on the
      vasculature. Acute exercise has been shown to alter MP concentrations, probably
      through a shear stress-dependent mechanism, but evidence is limited. Therefore,
      we investigated the effect of exercise intensity on plasma levels of CD34+ and
      CD62E+ MPs in young, healthy men and women. Blood samples were collected before,
      during and after two energy-matched bouts of acute treadmill exercise: interval
      exercise (10 * 1 min intervals at ~95% of maximal oxygen uptake VO2max) and
      continuous exercise (65% VO2max). Continuous exercise, but not interval exercise,
      reduced CD62E+ MP concentrations in men and women by 18% immediately after
      exercise (from 914.5 +/- 589.6 to 754.4 +/- 390.5 MPs MUl-1 ; P < 0.05),
      suggesting that mechanisms underlying exercise-induced CD62E+ MP dynamics are
      intensity dependent. Furthermore, continuous exercise reduced CD62E+ MPs in women
      by 19% (from 1030.6 +/- 688.1 to 829.9 +/- 435.4 MPs MUl-1 ; P < 0.05), but not
      in men. Although interval exercise did not alter CD62E+ MPs per se, the
      concentrations after interval exercise were higher than those observed after
      continuous exercise (P < 0.05). Conversely, CD34+ MPs did not fluctuate in
      response to short-duration acute continuous or interval exercise in men or women.
      Our results suggest that exercise-induced MP alterations are intensity dependent
      and sex specific and impact MP populations differentially.

PMID- 29469166
TI  - Spheroid-based 3D cell cultures identify salinomycin as a promising drug for the
      treatment of chondrosarcoma.
AB  - Chondrosarcoma (CS) is a cartilage malignancy of adulthood that is treated by
      surgery alone, since chemotherapy is considered ineffective. Unfortunately, a
      large proportion of patients with CS develop lung metastases, and several die of
      the disease. In this study, we compared 3D-spheroid cultures and conventional
      cell monolayer models in order to identify the best way to select anticancer
      agents that could be effective for the systemic control of CS. Using SW1353
      cells, we developed a three-dimensional (3D) in vitro culture model to mimic in
      vivo features of CS microenvironment and evaluated the efficacy of different
      drugs to modulate CS cell proliferation and survival in 2D versus 3D-cultures.
      Doxorubicin (DXR) and cisplatin, that are widely employed in sarcomas, were less
      effective on 3D-CS spheroids when compared to standard monolayer models, whereas
      treatment with the ionophore salinomycin (SAL) had a strong cytotoxic effect both
      on 2D and 3D-cultures. Furthermore, as demonstrated by the reduced viability and
      the enhanced DXR nuclear localization, SAL enhanced DXR cytotoxicity in 3D-CS
      spheroids also at sub-lethal doses. SAL activity on 3D-CS spheroids was mediated
      by a significant induction of apoptosis via caspase activation. This study
      demonstrates that preclinical tests significantly differ in monolayer and 3D
      cultures of CS cells. Using this approach, SAL, alone or, at sub-lethal
      concentrations, in combination with DXR, represents a promising agent for the
      systemic treatment of CS. (c) 2018 Orthopaedic Research Society. Published by
      Wiley Periodicals, Inc. J Orthop Res.

PMID- 29469167
TI  - Higher mortality rate in patients with heart failure who are taking commonly
      prescribed antidiabetic medications and achieve recommended levels of glycaemic
      control.
AB  - Current guidelines for diabetes recommend that physicians attain a glycated
      haemoglobin (HbA1c) concentration <=7.0%, but this target may not be applicable
      to those with heart failure. Fourteen studies in patients with chronic heart
      failure that examined the relationship between the level of HbA1c and risk of
      death specified whether HbA1c was influenced by treatment with antidiabetic
      medications. In patients with heart failure not receiving glucose-lowering drugs,
      the mortality rate was not higher among those with an HbA1c concentration <7.0%.
      By contrast, in patients who were treated with insulin, sulphonylureas and
      thiazolidinediones, an inverse or U-shaped relationship between HbA1c and the
      risk of death was generally observed, and mortality was lowest in patients with
      both heart failure and diabetes if the level of HbA1c was >7.0%. These studies
      suggest that patients with both heart failure and diabetes are at increased risk
      of death if they are prescribed certain glucose-lowering drugs to achieve levels
      of HbA1c <7.0%.

PMID- 29469168
TI  - Screening of key odorants and anthocyanin compounds of cv. Okuzgozu (Vitis
      vinifera L.) red wines with a free run and pressed pomace using GC-MS
      Olfactometry and LC-MS-MS.
AB  - The principal purpose of the present work is to characterize the aroma, aroma
      active, and anthocyanin profiles of Okuzgozu wines and to observe the effect of
      the pomace pressing technique on these parameters. A total of 58 and 59 volatile
      compounds were identified and quantified in free-run juice wine (FRW) and pressed
      pomace wine (PW). Alcohols were found as the most dominant group among aroma
      compounds followed by esters and acids. However, among all these compounds, only
      11 and 13 of them could be considered as key odorants in aromatic extracts of FRW
      and PW, respectively. According to GC-MS-O analysis, ethyl octanoate (fruity),
      phenyl ethyl acetate (fruity), and 2-phenyl ethanol (flowery) were found as the
      main contributors to the overall scent of both wines. Beyond the aroma profiles,
      anthocyanin contents of both types of wines were also investigated, and total 14
      and 15 anthocyanins were identified and quantified in FRW and PW. Malvidin-3
      glycoside and its acetyl and coumaroyl forms were identified as the dominant
      anthocyanins in both wines. It is worth noting the pressing application (2.0 atm)
      led to an increase of some unpleasant notes in the aroma providing chemical,
      pharmacy, and fermented aromas in wine. On the other hand, the wines produced
      with pressed pomace presented higher amounts of anthocyanins.

PMID- 29469169
TI  - Alimentary microbes of winter-form Drosophila suzukii.
AB  - Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) is a damaging pest of
      fruit. Reproductively diapausing adults overwinter in woodlands and remain active
      on warmer winter days. It is unknown if this adult phase of the lifecycle feeds
      during the winter period, and what the food source may be. This study
      characterized the flora in the digestive tract of D. suzukii using a metagenomics
      approach. Live D. suzukii were trapped in four woodlands in the south of England
      and their guts dissected for DNA extraction and amplicon-based metagenomics
      sequencing (internal transcribed spacer and 16S rRNA). Analysis at genus and
      family taxonomic levels showed high levels of diversity with no differences in
      digestive tract bacterial or fungal biota between woodland sites of winter-form
      D. suzukii. Female D. suzukii at one site appeared to have higher bacterial
      diversity in the alimentary canal than males, but there was a site, sex
      interaction. Many of the biota were associated with cold, wet climatic conditions
      and decomposition. This study provides the first evidence that winter-form D.
      suzukii may be opportunistic feeders during the winter period and are probably
      exploiting food sources associated with moisture on decomposing vegetation during
      this time. A core gut microbiome has been identified for winter-form D. suzukii.

PMID- 29469170
TI  - Is non-response to fluconazole maintenance therapy for recurrent Candida
      vaginitis related to sensitization to atopic reactions?
AB  - PROBLEM: Is sensitization to atopic reaction related to treatment response of
      recurrent Candida vulvovaginal (RVVC)? METHOD OF THE STUDY: Analysis of ReCiDiF
      trial data of optimal (OR) and non-responders (NR) to fluconazole maintenance
      treatment, to explore medical history, physical status, family history, and
      vaginal immune response for potential sensitization to atopic reaction. RESULTS:
      Sociodemographic characteristics of 33 NR women were not different from 38 OR. NR
      had received higher number of different treatments (mean difference 1.6 different
      treatments (95% CI: 0.20-2.97), P = .03) and had more episodes of disease (P <
      .05). Multivariate regression analysis showed that family history of atopy (OR:
      4.9, CI 95%: 1.1-22.2), duration of symptoms (OR: 1.2, CI 95%: 1.02-1.5), and
      vulvar excoriation (OR: 3.6, CI 95%: 1.4-9.3) were related to non-response.
      Vulvar excoriation at entry was the only statistically significant predictive
      factor for non-response in multivariate analysis with specificity 77.8% and
      sensitivity 51.6%. CONCLUSION: Women with RVVC with vulvar excoriation, longer
      duration of disease, and family history of atopic disease are at increased risk
      not to respond to maintenance fluconazole treatment.

PMID- 29469171
TI  - Quality management of nuchal translucency ultrasound measurement in Australia.
AB  - BACKGROUND: Nuchal translucency measurement has an established role in first
      trimester screening. Accurate measurement requires that technical guidelines are
      followed. Performance can be monitored by auditing the distribution of
      measurements obtained in a series of cases. AIMS: The primary aim is to develop
      an accessible, theory-based educational program for individuals whose
      distribution of measurements at audit falls outside an acceptable range, and
      assess operator performance following this intervention. MATERIALS AND METHODS:
      Operators whose nuchal translucency measurement distributions fall outside a
      normal range (38-65% above the median) were expected to undergo a teleconference
      tutorial. Accessible from anywhere in Australia, the one hour tutorials were run
      by a senior sonographer (to explain technical ultrasound aspects) and the audit
      program manager (to explain the audit process). RESULTS: In 2011, 83 operators
      attended the teleconference tutorials. Compared to a random comparison group of
      operators meeting standard in 2011, teleconference tutorial attendees were
      significantly more likely to: (i) operate in rural or regional, rather than
      metropolitan, centres (P = 0.001); (ii) be less experienced (P < 0.0005); and
      (iii) have lower annual scan numbers (P = 0.0012). Improvement in nuchal
      translucency measurement quality was seen after one audit cycle and was
      maintained over subsequent years. The mean percentage of the study cohort
      reaching standard over the five-year audit was 77.8% which was not statistically
      different from the average for the comparison cohort of all other audited
      operators (79.3%; P = 0.61). CONCLUSIONS: Teleconference tutorials are a
      convenient, accessible and effective way to obtain immediate and sustained
      improvement in operator performance.

PMID- 29469172
TI  - Segmentation of hip cartilage in compositional magnetic resonance imaging: A
      fast, accurate, reproducible, and clinically viable semi-automated methodology.
AB  - Manual segmentation is a significant obstacle in the analysis of compositional
      MRI for clinical decision-making and research. Our aim was to produce a fast,
      accurate, reproducible, and clinically viable semi-automated method for
      segmentation of hip MRI. We produced a semi-automated segmentation method for
      cartilage segmentation of hip MRI sequences consisting of a two step process: (i)
      fully automated hierarchical partitioning of the data volume generated using a
      bespoke segmentation approach applied recursively, followed by (ii) user
      selection of the regions of interest using a region editor. This was applied to
      dGEMRIC scans at 3T taken from a prospective longitudinal study of individuals
      considered at high-risk of developing osteoarthritis (SibKids) which were also
      manually segmented for comparison. Fourteen hips were segmented both manually and
      using our semi-automated method. Per hip, processing time for semi-automated and
      manual segmentation was 10-15, and 60-120 min, respectively. Accuracy and Dice
      similarity coefficient (DSC) for the comparison of semi-automated and manual
      segmentations was 0.9886 and 0.8803, respectively. Intra-observer and inter
      observer reproducibility of the semi-automated segmentation method gave an
      accuracy of 0.9997 and 0.9991, and DSC of 0.9726 and 0.9354, respectively. We
      have proposed a fast, accurate, reproducible, and clinically viable semi
      automated method for segmentation of hip MRI sequences. This enables accurate
      anatomical and biochemical measurements to be obtained quickly and reproducibly.
      This is the first such method that shows clinical applicability, and could have
      large ramifications for the use of compositional MRI in research and clinically.
      (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J
      Orthop Res.

PMID- 29469173
TI  - Synthesis of Supported Bimetal Catalysts using Galvanic Deposition Method.
AB  - Supported bimetallic catalysts have been studied because of their enhanced
      catalytic properties due to metal-metal interactions compared with monometallic
      catalysts. We focused on galvanic deposition (GD) as a bimetallization method,
      which achieves well-defined metal-metal interfaces by exchanging heterogeneous
      metals with different ionisation tendencies. We have developed Ni@Ag/SiO2
      catalysts for CO oxidation, Co@Ru/Al2 O3 catalysts for automotive three-way
      reactions and Pd-Co/Al2 O3 catalysts for methane combustion by using the GD
      method. In all cases, the catalysts prepared by the GD method showed higher
      catalytic activity than the corresponding monometallic and bimetallic catalysts
      prepared by the conventional co-impregnation method. The GD method provides
      contact between noble and base metals to improve the electronic state, surface
      structure and reducibility of noble metals.

PMID- 29469174
TI  - Membrane fluidification by ethanol stress activates unfolded protein response in
      yeasts.
AB  - The toxic effect of ethanol is one of the most important handicaps for many
      biotechnological applications of yeasts, such as bioethanol production.
      Elucidation of ethanol stress response will help to improve yeast performance in
      biotechnological processes. In the yeast Saccharomyces cerevisiae, ethanol stress
      has been recently described as an activator of the unfolded protein response
      (UPR), a conserved intracellular signalling pathway that regulates the
      transcription of ER homoeostasis-related genes. However, the signal and
      activation mechanism has not yet been unravelled. Here, we studied UPR's
      activation after ethanol stress and observed the upregulation of the key target
      genes, like INO1, involved in lipid metabolism. We found that inositol content
      influenced UPR activation after ethanol stress and we observed significant
      changes in lipid composition, which correlate with a major membrane fluidity
      alteration by this amphipathic molecule. Then, we explored the hypothesis that
      membrane fluidity changes cause UPR activation upon ethanol stress by studying
      UPR response against fluidification or rigidification agents and by studying a
      mutant, erg2, with altered membrane fluidity. The results suggest that the
      membrane fluidification effects of ethanol and other agents are the signal for
      UPR activation, a mechanism that has been proposed in higher eukaryotes.

PMID- 29469176
TI  - Current physiotherapy practice in the management of tennis elbow: A service
      evaluation.
AB  - BACKGROUND: Tennis elbow is a common painful condition that may affect daily
      function and ability to work. Physiotherapy is the most commonly used primary
      intervention but there is a wide range of treatment options within the umbrella
      of physiotherapy. Our aim was to report on the treatments that are currently used
      by physiotherapists in a UK National Health Service (NHS) setting. METHODS: A
      retrospective service evaluation was conducted at two NHS hospital trusts by
      reviewing patient attendance records over a 1-year period. All patients with
      tennis elbow were included, except those referred for postoperative
      rehabilitation. Patient notes were analysed using a predefined assessment
      template. RESULTS: A total of 65 patient records were identified, with patients
      having a mean age 48 years and mean symptom duration of 5.4 months. The mean
      treatment duration was 64 days, over 3.7 sessions. The most commonly used
      treatments were education and exercise, although the type and dosing of exercise
      varied greatly. Passive modalities such as ice, taping, manual therapy,
      acupuncture and electrotherapy were still used. CONCLUSIONS: Wide variations in
      treatment approaches were identified. There was no consistency in the choice of
      modality used, the type of exercise or the dose of exercise prescribed. The use
      of passive modalities and corticosteroid injections was found to remain
      commonplace, despite a lack of supporting research evidence. There is a clear
      need for evidence-based guidance for physiotherapists treating patients with
      tennis elbow.

PMID- 29469175
TI  - Presence of autoimmune disease affects not only risk but also survival in
      patients with B-cell non-Hodgkin lymphoma.
AB  - Although autoimmune diseases (AIDs) are known to predispose to non-Hodgkin
      lymphoma (NHL), their association with NHL prognosis has rarely been
      investigated. We examined associations between autoimmunity and B-cell NHL onset
      by comparing AID history (determined by self-report and medication review and
      supplemented by chart review where possible) among 435 adult B-NHL patients in
      Hadassah-Hebrew University Medical Center, diagnosed 2009-2014, and 414 age-and
      sex frequency-matched controls. We examined AIDs as a whole, B- and T-cell
      mediated AIDs, and autoimmune thyroid diseases. Among cases, we used Kaplan-Meier
      and Cox regression models to assess the association of AID with overall survival
      and relapse-free survival, adjusting for prognostically important patient and
      disease characteristics such as Ki67% staining, International Prognostic Index,
      rituximab treatment, and histological subgroup. Autoimmune diseases were
      associated with B-NHL (odds ratio [OR] = 1.95; 95% confidence interval (CI), 1.31
      2.92), especially AIDs mediated by B-cell activation (OR = 5.20; CI, 1.90-14.3),
      which were particularly associated with marginal zone lymphoma (OR = 19.3; CI,
      4.59-80.9). We found that time to relapse for all B-NHL patients with AIDs was
      significantly shorter (mean of 49.21 mo [+/-3.22]) than among patients without
      AID (mean of 59.74 mo [+/-1.62]), adjusted hazard ratio [HRadj ] = 1.69 (CI, 1.03
      2.79). Specifically, in patients with diffuse large B-cell lymphoma, of whom
      91.8% had received rituximab, a history of B-cell-mediated AIDs was associated
      with shorter relapse-free survival and overall survival, HRadj  = 8.34 (CI, 3.01
      23.1) and HRadj  = 3.83 (CI, 1.20-12.3), respectively. Beyond confirming the well
      known association between AIDs and B-NHL, we found that AID is an adverse
      prognostic factor in B-cell lymphoma, associated with a shortened time to
      relapse, suggesting that there are specific therapeutic challenges in the
      subgroup of patients suffering from both these diseases. Further work is required
      to address mechanisms of resistance to standard treatment in the setting of AID
      associated B-NHL. In the era of immunotherapy, these findings have particular
      relevance.

PMID- 29469177
TI  - Haemodynamic effects of levosimendan in advanced but stable chronic heart
      failure.
AB  - AIMS: Levosimendan improves haemodynamics in acute decompensated heart failure
      (HF). However, it is increasingly used for repetitive or intermittent infusions
      in advanced but stable chronic HF, without clear indication, selection criteria,
      or effect. We tested the hypotheses that (1) levosimendan improves haemodynamics
      in stable chronic HF and (2) that the response is dependent on baseline clinical
      and haemodynamic factors. METHODS AND RESULTS: Twenty-three patients [median age
      56 (49-64) years, four (17%) women] with stable New York Heart Association (NYHA)
      III and IV HF received a single 24 h levosimendan infusion. Non-invasive
      haemodynamics (inert gas re-breathing technique), estimated glomerular filtration
      rate, and N-terminal pro-brain natriuretic peptide were assessed before and after
      infusion. Levosimendan had the following effects (median change): a significant
      increase in cardiac output (+9.8 +/- 21.6%; P = 0.026) and decrease in N-terminal
      pro-brain natriuretic peptide (-28.1 +/- 16.3%, P < 0.001), estimated total
      peripheral resistance (-16.9 +/- 18.3%, P = 0.005), and mean arterial pressure (
      5.9 +/- 8.2%, P = 0.007), but no change in estimated glomerular filtration rate
      (+0.89 +/- 14.0%, P = 0.955). There were no significant associations between
      baseline clinical and/or haemodynamic factors and the levosimendan effect on
      cardiac output. CONCLUSIONS: Levosimendan was associated with improved
      haemodynamics in patients with stable chronic HF, but we could not identify any
      predictors of the magnitude of haemodynamic response.

PMID- 29469179
TI  - Novel Peroxides as Promising Anticancer Agents with Unexpected Depressed
      Antimalarial Activity.
AB  - Twenty six peroxides belonging to bridged 1,2,4,5-tetraoxanes, bridged 1,2,4
      trioxolanes (ozonides), and tricyclic monoperoxides were evaluated for their in
      vitro antimalarial activity against Plasmodium falciparum (3D7) and for their
      cytotoxic activities against immortalized human normal fibroblast (CCD19Lu),
      liver (LO2 ), and lung (BEAS-2B) cell lines as well as human liver (HepG2) and
      lung (A549) cancer-cell lines. Synthetic ozonides were shown to have the highest
      cytotoxicity on HepG2 (IC50 =0.19-0.59 MUm), and some of these compounds
      selectively targeted liver cancer (selectivity index values for compounds 13 a
      and 14 a are 20 and 28, respectively) at levels that, in some cases, were higher
      than those of paclitaxel, artemisinin, and artesunic acid. In contrast some
      ozonides showed only moderate antimalarial activity against the chloroquine
      sensitive 3D7 strain of P. falciparum (IC50 from 2.76 to 24.2 MUm; 12 b, IC50
      =2.76 MUm; 13 a, IC50 =20.14 MUm; 14 a, IC50 =6.32 MUm). These results suggest
      that these derivatives have divergent mechanisms of action against cancer cells
      and malaria-infected cells. A cyclic voltammetry study of the peroxides was
      performed, but most of the compounds did not show direct correlation in oxidative
      capacity-activity. Our findings offer a new source of antimalarial and anticancer
      agents through structural modification of peroxide compounds.

PMID- 29469180
TI  - Hybrid Graphene-Polyoxometalates Nanofluids as Liquid Electrodes for Dual Energy
      Storage in Novel Flow Cells.
AB  - Solid Hybrid materials abound. But flowing versions of them are new actors in the
      materials science landscape and in particular for energy applications. This paper
      presents a new way to deliver nanostructured hybrid materials for energy storage,
      namely, in the form of nanofluids. We present here the first example of a hybrid
      electroactive nanofluid (HENFs) combining capacitive and faradaic energy storage
      mechanisms in a single fluid material. This liquid electrode is composed of
      reduced graphene oxide and polyoxometalates (rGO-POMs) forming a stable
      nanocomposite for electrochemical energy storage in novel Nanofluid Flow Cells.
      Two graphene based hybrid materials (rGO-phosphomolybdate, rGO-PMo12 and rGO
      phosphotungstate, rGO-PW12 ) were synthesized and dispersed with the aid of a
      surfactant in 1 M H2 SO4 aqueous electrolyte to yield highly stable hybrid
      electroactive nanofluids (HENFs) of low viscosity which were tested in a home
      made flow cell under static and continuous flowing conditions. Remarkably, even
      low concentration rGO-POMs HENFs (0.025 wt%) exhibited high specific capacitances
      of 273 F/g(rGO-PW12 ) and 305 F/g(rGO-PMo12 ) with high specific energy and
      specific power. Moreover, rGO-POM HENFs show excellent cycling stability (~95 %)
      as well as Coulombic efficiency (~77-79 %) after 2000 cycles. Thus, rGO-POM HENFs
      effectively behave as real liquid electrodes with excellent properties,
      demonstrating the possible future application of HENFs for dual energy storage in
      a new generation of Nanofluid Flow Cells.

PMID- 29469181
TI  - Lymphocyte immunotherapy for recurrent miscarriages: Predictors of therapeutic
      success.
AB  - PROBLEM: To evaluate the predictors of successful pregnancies in women with a
      history of recurrent miscarriages (RMs) having undergone lymphocyte immunotherapy
      (LIT). METHOD OF STUDY: Retrospective, multicenter, observational study which
      involved 702 pregnant women with history of RM treated with LIT. Comparative
      analysis of women with a history of RM having undergone LIT and experienced
      treatment success vs those having experienced treatment failure along with the
      analysis of the association between the number of prior miscarriages and the
      efficacy of LIT. RESULTS: A total of 421 women were able to carry the pregnancy
      to term, with treatment success rate of 60%. The multivariate analysis showed
      that age, the association between autoantibodies and thrombophilia, and the
      number of previous miscarriages were factors associated with LIT failure.
      Secondary RMs alone were not found to be a factor predictive of LIT success or
      failure; however, secondary RMs among women with a history of 5 or more RM were
      found to be a predictor of LIT success (OR: 10.24; 95% CI: 1.9-55.8; P = .007).
      CONCLUSION: Age, the number of previous miscarriages, and the association between
      autoantibodies and thrombophilia are associated with LIT failure. A higher number
      of previous miscarriages in cases of secondary RM resulted in better LIT
      outcomes.

PMID- 29469182
TI  - Identification of the novel allele, HLA-A*01:234, in the mother of a German cord
      blood donor.
AB  - HLA-A*01:234 was identified by next-generation sequencing and confirmed by Sanger
      sequencing.

PMID- 29469183
TI  - The [2+2] Cycloaddition-Retroelectrocyclization (CA-RE) Click Reaction: Facile
      Access to Molecular and Polymeric Push-Pull Chromophores.
AB  - The [2+2] cycloaddition-retroelectrocyclization (CA-RE) reaction between electron
      rich alkynes and electron-deficient alkenes is an efficient procedure to create
      nonplanar donor-acceptor (D-A) chromophores in both molecular and polymeric
      platforms. They feature attractive properties including intramolecular charge
      transfer (ICT) bands, nonlinear optical properties, and redox activities for use
      in next-generation electronic and optoelectronic devices. This Review summarizes
      the development of the CA-RE reaction, starting from the initial reports with
      organometallic compounds to the extension to purely organic systems. The
      structural requirements for rapid, high-yielding transformations with true click
      chemistry character are illustrated by examples that include the broad alkyne and
      alkene substitution modes. The CA-RE click reaction has been successfully applied
      to polymer synthesis, with the resulting polymeric push-pull chromophores finding
      many interesting applications.

PMID- 29469184
TI  - Low molecular weight heparin does not increase bleeding and mortality post
      endoscopic variceal band ligation in cirrhotic patients.
AB  - BACKGROUND & AIMS: Anticoagulants are commonly indicated in cirrhotic patients
      due to high rate of (pro)thrombotic conditions. Low molecular weight heparin
      (LMWH) is safe in patients with esophageal varices. However, the safety of LMWH
      is unknown in patients undergoing prophylactic endoscopic variceal ligation
      (EVL). To define the 4-week risk of bleeding and death after prophylactic EVL in
      cirrhotic patients continuously treated with LMWH. METHODS: All EVLs performed at
      a tertiary Italian Center from 2009 to 2016 were retrospectively reviewed.
      Patients treated with LMWH were classified as on-LMWH; the remaining as no-LMWH.
      Endoscopic characteristics at first and index EVL (that preceding an endoscopy
      either showing a bleeding episode or the absence of further treatable varices)
      and clinical events within 4 weeks from the procedures were recorded. RESULTS AND
      CONCLUSIONS: Five hundred fifty-three EVLs were performed in 265 patients (in 215
      as a primary prophylaxis): 169 EVLs in 80 on-LMWH and 384 in 185 no-LMWH (4.9 +/-
      1.1 vs 4.8 +/- 1.0 bands/session, respectively; P = .796). Six patients bled
      (2.2%) without between-groups difference (3.8% on-LMWH vs 1.6% no-LMWH, Log-rank
      P = .291). Large varices with red marks (100% vs 51.4%, P = .032), number of
      bands (5.6 +/- 0.5 vs 4.6 +/- 1.2, P = .004), underlying portal vein thrombosis
      (66.7% vs 23.6%, P = .033), and creatinine (2.2 +/- 2.7 vs 1.0 +/- 0.8 mg/dL, P =
      .001) at index EVL were significantly different between bleeders and non
      bleeders. Six patients died within 4-week from index EVL, without between-groups
      difference (2.5% on-LMWH vs 2.2% no-LMWH, Log-rank P = .863). LMWH does not
      increase the risk of post-procedural bleeding and does not affect survival of
      cirrhotic patients undergoing prophylactic EVL.

PMID- 29469185
TI  - Generalized lymphatic anomaly presenting as rhinorrhea and chylous pericardial
      effusion.

PMID- 29469187
TI  - The prediction of cyclic proximal humerus fracture fixation failure by various
      bone density measures.
AB  - Fixation of osteoporotic proximal humerus fractures has remained challenging, but
      may be improved by careful pre-operative planning. The aim of this study was to
      investigate how well the failure of locking plate fixation of osteoporotic
      proximal humerus fractures can be predicted by bone density measures assessed
      with currently available clinical imaging (realistic case) and a higher
      resolution and quality modality (theoretical best-case). Various density measures
      were correlated to experimentally assessed number of cycles to construct failure
      of plated unstable low-density proximal humerus fractures (N = 18). The influence
      of density evaluation technique was investigated by comparing local (peri
      implant) versus global evaluation regions; HR-pQCT-based versus clinical QCT
      based image data; ipsilateral versus contralateral side; and bone mineral content
      (BMC) versus bone mineral density (BMD). All investigated density measures were
      significantly correlated with the experimental cycles to failure. The best
      performing clinically feasible parameter was the QCT-based BMC of the
      contralateral articular cap region, providing significantly better correlation
      (R2  = 0.53) compared to a previously proposed clinical density measure (R2  =
      0.30). BMC had consistently, but not significantly stronger correlations with
      failure than BMD. The overall best results were obtained with the ipsilateral HR
      pQCT-based local BMC (R2  = 0.74) that may be used for implant optimization.
      Strong correlations were found between the corresponding density measures of the
      two CT image sources, as well as between the two sides. Future studies should
      investigate if BMC of the contralateral articular cap region could provide
      improved prediction of clinical fixation failure compared to previously proposed
      measures. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals,
      Inc. J Orthop Res.

PMID- 29469186
TI  - Serum brain-derived neurotrophic factor in children with coeliac disease.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has a
      protective role in the nervous system and is involved in neural plasticity. It is
      abundant in the central nervous system, but is also expressed in the
      gastrointestinal tract. Coeliac disease (CD), characterised by intestinal
      inflammation, has some comorbidity with neurologic and mental disorders. The aim
      of this study was to evaluate circulating BDNF concentrations in patients with CD
      at diagnosis or on a gluten-free diet (GFD) for longer than 1 year and in healthy
      controls (HC). MATERIALS AND METHODS: Fifty newly diagnosed patients with CD
      (aged 8.6 +/- 3.7 years, 64.0% females), thirty-nine patients on GFD for longer
      than 1 year (aged 10.4 +/- 3.4 years, 71.8% females) and 36 HC (aged 8 +/- 1.7
      years, 33.3% females) were included in the study. Along with anthropometric
      evaluation and standard blood chemistry, serum BDNF levels were measured by a
      specific immunoenzymatic assay. RESULTS: Patients at diagnosis and on GFD had
      significantly higher BDNF levels (26 110 +/- 8204 and 28 860 +/- 7992 pg/mL),
      respectively, than HC (19 630 +/- 8093 pg/mL, P < .001 for both CD groups).
      Patients on GFD had significantly higher BDNF levels than those at diagnosis (P =
      .02). CONCLUSIONS: Serum BDNF concentrations were higher in patients with CD than
      in HC, regardless of their status of gluten consumption. This could be attributed
      either to a potential protective response to the inflammation of the intestine or
      to chronic stress.

PMID- 29469188
TI  - Indeterminate cell histiocytosis in a Chinese patient with progressive and
      extensive nodular lesions and mixed indeterminate cell and macrophage-monocyte
      lineage.
AB  - Indeterminate cell histiocytosis (ICH) is an extremely rare cutaneous neoplastic
      disorder. It has the immunophenotypic features of both Langerhans and non
      Langerhans cell histiocytosis. We report here a case of a healthy young Chinese
      woman who presented with disfiguring, thick, infiltrated cutaneous nodules on the
      face, trunk and extremities which appeared progressively over a period of 4
      years. No systemic involvement has been detected so far. Results of a skin biopsy
      showed diffuse dermal infiltration of histiocytoid cells with indented nuclei and
      positive staining for S100 and CD1a and negativity for CD207 (langerin). Admixed
      within were some CD68-positive foamy histiocytes and multinucleated giant cells
      with focal expression of CD163. Although the clinical presentation is more
      typical of progressive nodular histiocytosis, the histology and immunoprofile is
      consistent with ICH. Our report adds to the limited case reports in the current
      literature of ICH in the Chinese population.

PMID- 29469190
TI  - Prognostic significance of platelet-to-lymphocyte ratio in patients with ovarian
      cancer: A meta-analysis.
AB  - BACKGROUND: The platelet-to-lymphocyte ratio (PLR) has been found to predict
      clinical outcomes in borderline ovarian tumours and the other genital neoplasms.
      However, its prognostic value in patients with ovarian cancer remains
      controversial. The aim of this study was to assess its prognostic value in
      ovarian cancer. METHODS: We searched MEDLINE, EMBASE and the Cochrane databases
      to identify studies evaluating the prognostic significance of pretreatment PLR in
      ovarian cancer. The end points were overall survival (OS) and progression-free
      survival (PFS). Pooled hazard ratios (HRs) with 95% confidence intervals (CIs)
      were calculated using fixed-effects/random-effects models. RESULTS: A total of 11
      studies comprising 3574 patients with ovarian cancer were included. The random
      effects meta-analysis demonstrated that patients with elevated PLR had shorter OS
      (HR: 1.48, 95% CI: 1.24-1.76, P < .001) and PFS (HR: 1.38, 95% CI: 1.17-1.63, P <
      .001). The negative prognostic impact of high PLR on OS and PFS remained
      substantial in Asian populations, patients with PLR >= 200 and studies with NOS
      score >= 7. CONCLUSIONS: Elevated pretreatment PLR could be an unfavourable
      prognostic factor for clinical outcomes in patients with ovarian cancer.

PMID- 29469189
TI  - Incorporation of GSTA1 genetic variations into a population pharmacokinetic model
      for IV busulfan in paediatric hematopoietic stem cell transplantation.
AB  - AIMS: The aim of this study is to develop a population pharmacokinetic (PopPK)
      model for intravenous busulfan in children that incorporates variants of GSTA1,
      gene coding for the main enzyme in busulfan metabolism. METHODS: Busulfan
      concentration-time data was collected from 112 children and adolescents (median
      5.4 years old, range: 0.1-20) who received intravenous busulfan during the
      conditioning regimen prior to stem cell transplantation. Weight, sex, baseline
      disease (malignant vs. non-malignant), age, conditioning regimen and GSTA1
      diplotypes were evaluated as covariates of pharmacokinetic parameters by using
      nonlinear mixed effects analysis. The ability to achieve the target AUC24h (3600
      6000 MUM min-1 ) was assessed by estimating the first dose based on the present
      PopPK model and by comparing the results with other available models in children.
      RESULTS: A one-compartment model with first-order elimination best described the
      data. Allometric scaling of weight and a factor of busulfan metabolism maturation
      were included in the base model. GSTA1 diplotypes were found to be a significant
      covariate of busulfan clearance, which was 7% faster in rapid metabolizers and
      12% slower in poor metabolizers, in comparison with normal ones. Busulfan doses
      calculated using the parameters of the proposed PopPK model were estimated to
      achieve the target AUC in 85.2% of the cases (95% CI 78.7-91.7%). CONCLUSION:
      This is the first PopPK for busulfan that successfully incorporated GSTA1
      genotype in a paediatric population. Its use may contribute to better prediction
      of busulfan exposure in children and adolescents since the first dose, by
      tailoring the dose according to the individual metabolic capacity.

PMID- 29469191
TI  - Sensor Technologies Empowered by Materials and Molecular Innovations.
AB  - Functional synthetic designer materials can impact many advanced technologies,
      and the chemical sensor area is intimately reliant on these new chemical
      innovations. The transduction of chemical and biological signals is necessary for
      low cost omnipresent chemical sensing and will be realized by chemical designs of
      new transduction materials. We are poised for many new innovations to empower new
      generations of sensor technologies. Materials innovations promise to expand the
      capabilities of present hardware, drive down the cost, and ensure broad
      implementation of these methods.

PMID- 29469192
TI  - GATA6-positive lung adenocarcinomas are associated with invasive mucinous
      adenocarcinoma morphology, hepatocyte nuclear factor 4alpha expression, and KRAS
      mutations.
AB  - AIMS: GATA6 is known to play a role in lung development. However, its role in the
      carcinogenesis of lung cancer is not well studied. The aim of this study was to
      analyse GATA6 expression in lung adenocarcinomas (LAs) by immunohistochemistry
      (IHC) in order to define its association with clinicopathological
      characteristics. METHODS AND RESULTS: IHC analysis of GATA6 was performed with
      tissue microarray slides containing 348 LAs. The association between GATA6
      expression and clinicopathological parameters was evaluated. GATA6 expression in
      epithelial tumours other than lung cancer was also evaluated. GATA6 expression
      was found in 47 LAs (13.5%). This occurred more frequently in younger patients (P
      = 0.005), and was associated with the absence of lymph node metastasis (P
      =0.024), well-differentiated to moderately differentiated tumours (P < 0.001),
      the absence of lymphatic invasion (P = 0.020), and the absence of vascular
      invasion (P = 0.011). GATA6 expression was associated with mucin production (P <
      0.001), the invasive mucinous adenocarcinoma subtype (P < 0.001), KRAS mutations
      (P = 0.026), expression of MUC2 (P < 0.001), CDX2 (P = 0.049), and MUC5AC (P <
      0.001), and absence of expression of TTF-1 (P = 0.002). GATA6 expression was also
      associated with hepatocyte nuclear factor 4alpha (HNF4alpha) expression (P <
      0.001). GATA6 expression tended to indicate better prognoses, whereas patients
      with HNF4alpha expression had significantly worse prognoses (P = 0.033). Of 270
      tumours other than lung cancer, 110 expressed GATA6. CONCLUSIONS: These findings
      suggest that GATA6 might interact with HNF4alpha and contribute to the
      development of mucinous-type LAs.

PMID- 29469194
TI  - "Existential Fridays"-reflection in action.

PMID- 29469195
TI  - Postoperative ileus following major colorectal surgery.
AB  - BACKGROUND: Postoperative ileus (POI) is characterized by delayed
      gastrointestinal recovery following surgery. Current knowledge of
      pathophysiology, clinical interventions and methodological challenges was
      reviewed to inform modern practice and future research. METHODS: A systematic
      search of MEDLINE and Embase databases was performed using search terms related
      to ileus and colorectal surgery. All RCTs involving an intervention to prevent or
      reduce POI published between 1990 and 2016 were identified. Grey literature, non
      full-text manuscripts, and reanalyses of previous RCTs were excluded. Eligible
      articles were assessed using the Cochrane tool for assessing risk of bias.
      RESULTS: Of 5614 studies screened, 86 eligible articles describing 88 RCTs were
      identified. Current knowledge of pathophysiology acknowledges neurogenic,
      inflammatory and pharmacological mechanisms, but much of the evidence arises from
      animal studies. The most common interventions tested were chewing gum (11 trials)
      and early enteral feeding (11), which are safe but of unclear benefit for
      actively reducing POI. Others, including thoracic epidural analgesia (8),
      systemic lidocaine (8) and peripheral MU antagonists (5), show benefit but
      require further investigation for safety and cost-effectiveness. CONCLUSION: POI
      is a common condition with no established definition, aetiology or treatment.
      According to current literature, minimally invasive surgery, protocol-driven
      recovery (including early feeding and opioid avoidance strategies) and measures
      to avoid major inflammatory events (such as anastomotic leak) offer the best
      chances of reducing POI.

PMID- 29469193
TI  - Toward sustainable environmental quality: Identifying priority research questions
      for Latin America.
AB  - The Global Horizon Scanning Project (GHSP) is an innovative initiative that aims
      to identify important global environmental quality research needs. Here we report
      20 key research questions from Latin America (LA). Members of the Society of
      Environmental Toxicology and Chemistry (SETAC) LA and other scientists from LA
      were asked to submit research questions that would represent priority needs to
      address in the region. One hundred questions were received, then partitioned
      among categories, examined, and some rearranged during a workshop in Buenos
      Aires, Argentina. Twenty priority research questions were subsequently
      identified. These research questions included developing, improving, and
      harmonizing across LA countries methods for 1) identifying contaminants and
      degradation products in complex matrices (including biota); 2) advancing
      prediction of contaminant risks and effects in ecosystems, addressing lab-to
      field extrapolation challenges, and understanding complexities of multiple
      stressors (including chemicals and climate change); and 3) improving management
      and regulatory tools toward achieving sustainable development. Whereas
      environmental contaminants frequently identified in these key questions were
      pesticides, pharmaceuticals, endocrine disruptors or modulators, plastics, and
      nanomaterials, commonly identified environmental challenges were related to
      agriculture, urban effluents, solid wastes, pulp and paper mills, and natural
      extraction activities. Several interesting research topics included assessing and
      preventing pollution impacts on conservation protected areas, integrating
      environment and health assessments, and developing strategies for identification,
      substitution, and design of less hazardous chemicals (e.g., green chemistry).
      Finally, a recurrent research need included developing an understanding of
      differential sensitivity of regional species and ecosystems to environmental
      contaminants and other stressors. Addressing these critical questions will
      support development of long-term strategic research efforts to advance more
      sustainable environmental quality and protect public health and the environment
      in LA. Integr Environ Assess Manag 2018;14:344-357. (c) 2018 The Authors.
      Integrated Environmental Assessment and Management published by Wiley
      Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry
      (SETAC).

PMID- 29469196
TI  - The relationship between inflammation and remodeling in childhood asthma: A
      systematic review.
AB  - OBJECTIVES: We aimed to perform a systematic review of all studies with direct
      measurements of both airway inflammation and remodeling in the subgroup of
      children with repeated wheezing and/or persistent asthma severe enough to warrant
      bronchoscopy, to address whether airway inflammation precedes remodeling or is a
      parallel process, and also to assess the impact of remodeling on lung function.
      METHODS: Four databases were searched up to June 2017. Two independent reviewers
      screened the literature and extracted relevant data. RESULTS: We found 526
      references, and 39 studies (2390 children under 18 years old) were included.
      Airway inflammation (eosinophilic/neutrophilic) and remodeling were not present
      in wheezers at a mean age of 12 months, but in older pre-school children (mean
      2.5 years), remodeling (mainly increased reticular basement membrane [RBM]
      thickness and increased area of airway smooth muscle) and also airway
      eosinophilia was reported. This was worse in school-age children. RBM thickness
      was similar in atopic and non-atopic preschool wheezers. Airway remodeling was
      correlated with lung function in seven studies, with FeNO in three, and with HRCT
      scan in one. Eosinophilic inflammation was not seen in patients without
      remodeling. There were no invasive longitudinal or intervention studies.
      CONCLUSION: The relationship between inflammation and remodeling in children
      cannot be determined. Failure to demonstrate eosinophilic inflammation in the
      absence of remodeling is contrary to the hypothesis that inflammation causes
      these changes. We need reliable, non-invasive markers of remodeling in particular
      if this is to be addressed.

PMID- 29469197
TI  - Physiologically-based pharmacokinetic modelling of a CYP2C19 substrate, BMS
      823778, utilizing pharmacogenetic data.
AB  - AIMS: Previous studies demonstrated direct correlation between CYP2C19 genotype
      and BMS-823778 clearance in healthy volunteers. The objective of the present
      study was to develop a physiologically-based pharmacokinetic (PBPK) model for BMS
      823778 and use the model to predict PK and drug-drug interaction (DDI) in virtual
      populations with multiple polymorphic genes. METHODS: The PBPK model was built
      and verified using existing clinical data. The verified model was simulated to
      predict PK of BMS-823778 and significance of DDI with a strong CYP3A4 inhibitor
      in subjects with various CYP2C19 and UGT1A4 genotypes. RESULTS: The verified PBPK
      model of BMS-823778 accurately recovered observed PK in different populations. In
      addition, the model was able to capture the exposure differences between subjects
      with different CYP2C19 genotypes. PK simulation indicated higher exposures of BMS
      823778 in CYP2C19 poor metabolizers who were also devoid of UGT1A4 activity,
      compared to those with normal UGT1A4 functionality. Moderate DDI with
      itraconazole was predicted in subjects with wild-type CYP2C19 or UGT1A4. However,
      in subjects without CYP2C19 or UGT1A4 functionality, significant DDI was
      predicted when BMS-823778 was coadministered with itraconazole. CONCLUSIONS: A
      PBPK model was developed using clinical data that accurately predicted human PK
      in different population with various CYP2C19 phenotypes. Simulations with the
      verified PBPK model indicated that UGT1A4 was probably an important clearance
      pathway in CYP2C19 poor metabolizers. DDI with itraconazole is likely to be
      dependent on the genotypes of CYP2C19 and UGT1A4.

PMID- 29469198
TI  - Dose-escalation is needed for gross disease in high-risk neuroblastoma.
AB  - BACKGROUND: Locoregional failure is common after subtotal resection in high-risk
      neuroblastoma. Although a dose of 21 Gy radiation therapy (RT) is standard for
      treatment of high-risk neuroblastoma after gross total resection, the dose needed
      for local control of patients with gross residual disease at the time of RT is
      unknown. We sought to evaluate local control after 21-36 Gy RT in patients with
      high-risk neuroblastoma undergoing subtotal resection. METHODS: All patients with
      high-risk neuroblastoma who received RT to their primary site from 2000 to 2016
      were reviewed. Of the 331 patients who received consolidative RT to their primary
      site, 19 (5.7%) underwent subtotal resection and were included in our analysis.
      Local failure (LF) was correlated with biologic prognostic factors and dose of
      RT. RESULTS: Median follow-up among surviving patients was 6.0 years. Median RT
      dose was 25 Gy (range, 21 Gy-36 Gy). The 5-year cumulative incidence of LF among
      all patients was 17.2%. LF at 5 years was 30% in those who received <30 Gy versus
      0% in those who received 30-36 Gy (P = 0.12). There was a trend towards improved
      local control in patients with tumor size <=10 cm at diagnosis (P = 0.12). The 5
      year event-free and overall survival were 44.9% and 68.7%, respectively.
      CONCLUSION: After subtotal resection, patients who received less than 30 Gy had
      poor local control. Doses of 30-36 Gy are likely needed for optimal control of
      gross residual disease at the time of consolidative RT in high-risk
      neuroblastoma.

PMID- 29469199
TI  - Elucidation of the origin of 'agriocrithon' based on domestication genes
      questions the hypothesis that Tibet is one of the centers of barley
      domestication.
AB  - Wild barley forms a two-rowed spike with a brittle rachis whereas domesticated
      barley has two- or six-rowed spikes with a tough rachis. Like domesticated
      barley, 'agriocrithon' forms a six-rowed spike; however, the spike is brittle as
      in wild barley, which makes the origin of agriocrithon obscure. Haplotype
      analysis of the Six-rowed spike 1 (vrs1) and Non-brittle rachis 1 (btr1) and 2
      (btr2) genes was conducted to infer the origin of agriocrithon barley. Some
      agriocrithon barley accessions (eu-agriocrithon) carried Btr1 and Btr2 haplotypes
      that are not found in any cultivars, implying that they are directly derived from
      wild barley through a mutation at the vrs1 locus. Other agriocrithon barley
      accessions (pseudo-agriocrithon) carried Btr1 or Btr2 from cultivated barley,
      thus implying that they originated from hybridization between six-rowed landraces
      carrying btr1Btr2 and Btr1btr2 genotypes followed by recombination to produce
      Btr1Btr2. All materials we collected from Tibet belong to pseudo-agriocrithon and
      thus do not support the Tibetan Plateau as being a center of barley
      domestication. Tracing the evolutionary history of these allelic variants
      revealed that eu-agriocrithon represents six-rowed barley lineages that were
      selected by early farmers, once in south-eastern Turkmenistan (vrs1.a1) and again
      in the eastern part of Uzbekistan (vrs1.a4).

PMID- 29469200
TI  - Mutiple DICER1-related lesions associated with a germline deep intronic mutation.
AB  - Germline DICER1 pathogenic variants predispose to numerous benign and malignant
      tumors. In this report, we describe DICER1 gene analysis in an adolescent
      diagnosed with multinodular goiter, ovarian Sertoli-Leydig cell tumor, and lung
      cyst. DICER1 mutational screening at the DNA level failed to detect any
      pathogenic variant. Subsequent messenger RNA (mRNA) analysis revealed a 132
      nucleotide intronic sequence exonization. This truncating event was caused by a
      deep intronic mutation generating a de novo acceptor splice site. This study
      demonstrates that some undetected DICER1 mutations should be investigated at the
      mRNA level.

PMID- 29469201
TI  - Dynamics of Mechanosensitive Neural Stem Cell Differentiation.

PMID- 29469202
TI  - Bilateral pulmonary thrombosis in a newborn with congenital nephrotic syndrome.
AB  - In the neonatal period, pulmonary thromboembolic episodes are rare and unknown
      events. Case of a preterm newborn who presented a bilateral thrombosis of the
      pulmonary arteries associated with a congenital nephrotic syndrome. Pediatricians
      should consider pulmonary thromboembolic episodes in cases of newborns with
      unexplained severe and hypoxic respiratory distress syndrome.

PMID- 29469203
TI  - Coupling imaged capillary isoelectric focusing with mass spectrometry using a
      nanoliter valve.
AB  - Imaged capillary isoelectric focusing (iCIEF) is a powerful separation technique
      applied frequently for the analysis of biotherapeutics. However, direct mass
      spectrometric characterization is usually not possible. Here, focused peaks from
      an iCIEF system are transferred to a four-port nanoliter valve where peaks of
      interest are cut and transferred directly (flow injection) or via capillary zone
      electrophoresis to electrospray mass spectrometry. At first, flow injection
      coupling was tested with a mixture of peptides showing intraday precision (RSD)
      of 20.0 and 3.4% in area and 15.2 and 6.3% in intensity for angiotensin I and
      leucine-enkephalin, respectively. For the analysis of charge variants in an
      intact mAb, flow injection and CZE as second dimension were compared,
      demonstrating the usability of flow injection even for large proteins. However,
      improved spectra quality was achieved when CZE-MS was applied. In this way,
      accurate masses were obtained not only for the main isoform, but also for the
      main acidic and basic variants. These results demonstrate the power of iCIEF-CZE
      MS for the analysis of biotherapeutics.

PMID- 29469204
TI  - Plasma ammonia concentration after L-asparaginase therapy in 27 dogs with high
      grade lymphoma or leukemia.
AB  - OBJECTIVES: To establish the occurrence of increased plasma ammonia concentration
      after L-asparaginase (L-asp) administration in dogs with high-grade lymphoma or
      leukemia; to identify risk factors for the development of hyperammonemia after L
      asp administration; and to determine occurrence of adverse events related to
      hyperammonemia. DESIGN: Prospective case controlled study of sequentially
      enrolled dogs between May 2011 and March 2012. SETTING: A university veterinary
      teaching hospital. ANIMALS: Twenty-seven dogs with high-grade lymphoma or
      leukemia. INTERVENTIONS: All dogs received L-asp intramuscularly at a median dose
      of 400 IU/kg. MEASUREMENTS AND MAIN RESULTS: Plasma ammonia concentrations were
      measured at baseline, 16 hours, and 48 hours after L-asp therapy.
      Clinicopathological abnormalities were assessed to determine risk factors for the
      development of hyperammonemia. Adverse events following L-asp were recorded.
      Median plasma ammonia concentrations at baseline, 16 hours, and 48 hours were 26
      MUmol/L (44 MUg/dL), 98 MUmol/L (166.9 MUg/dL), and 67 MUmol/L (114 MUg/dL),
      respectively. Median plasma ammonia concentrations at 16 and 48 hours after
      administration were significantly increased compared to baseline. Six dogs had
      adverse events following L-asp administration. No significant clinical signs were
      noted that could clearly be attributed to hyperammonemia. No risk factors for
      developing hyperammonemia were identified; however, there was a positive
      correlation between the development of hyperammonemia at 16- and 48-hour time
      points. CONCLUSIONS: Subclinical hyperammonemia in dogs with lymphoma or leukemia
      after L-asp administration appears to be common. No risk factors were identified
      for the development of hyperammonemia after L-asp treatment, and severe adverse
      events were rare.

PMID- 29469205
TI  - The diagnostic value of cell blocks in Liquid-Based Cytology of bronchial
      aspiration and bronchial brushing materials.
AB  - INTRODUCTION: Fibreoptic bronchoscopy is used for the diagnosis and treatment of
      several pulmonary diseases. Conventional smear and Liquid-based cytology (LBC)
      methods are applied to cytology samples of various bronchoscopic techniques. If
      the cytology sample is sufficient for evaluation, a cell block (CB) can be
      prepared from the remaining material. The aim of this study is to identify the
      diagnostic value of conventional smear, LBC and CB methods in bronchial
      cytological specimens. METHODS: A retrospective review of 329 samples from 240
      patients was made and, of these, 144 patients were found to have neoplasia. A
      blind review of the specimens was performed and all were reclassified
      individually. The endoscopic findings of the 144 patients with neoplasia were
      analysed retrospectively. The cytological diagnoses were then compared with the
      final diagnosis or the endoscopic findings of patients with neoplasia. The
      sensitivity was calculated for each method, both separately and together.
      RESULTS: It was determined that CB led to a 10.1% increase in the diagnostic
      sensitivity for bronchial aspiration (BA) specimens, while no significant
      increase was seen in bronchial brush specimens. In BA specimens of neoplasia
      patients with normal bronchoscopic findings, while three methods were applied
      together with an increase in the number of cases diagnosed as malignant cytology,
      there was no significant increase in bronchial brush specimens. CONCLUSION: This
      study demonstrated that adding cell block to CB and LBC seemed to contribute the
      cytological diagnosis in BA materials significantly. Another advantage of CB is
      the opportunity of applying advanced methods such as immunocytochemical and
      molecular techniques.

PMID- 29469206
TI  - Impact of sacubitril-valsartan combination in patients with chronic heart failure
      and sleep apnoea syndrome: the ENTRESTO-SAS study design.
AB  - AIMS: Sleep-disordered breathing (SDB) is a highly prevalent co-morbidity in
      patients with chronic heart failure (CHF) and can play a detrimental role in the
      pathophysiology course of CHF. However, the best way to manage SDB in CHF remains
      a matter of debate. Sacubitril-valsartan has been included in the 2016 European
      Society of Cardiology guidelines as an alternative to angiotensin-converting
      enzyme inhibitors to further reduce the risk of progression of CHF, CHF
      hospitalization, and death in ambulatory patients. Sacubitril and valsartan are
      good candidates for correcting SDB of CHF patients because their known mechanisms
      of action are likely to counteract the pathophysiology of SDB in CHF. METHODS AND
      RESULTS: The ENTRESTO-SAS trial is a 3-month, multicentric, prospective, open
      label real-life cohort study. Patients eligible for sacubitril-valsartan
      treatment (i.e. adults with left ventricular ejection fraction <=35%, who remain
      symptomatic despite optimal treatment with an angiotensin-converting enzyme
      inhibitor, a beta-blocker, and a mineralocorticoid receptor antagonist) will be
      evaluated before and after 3 months of treatment (nocturnal ventilatory
      polygraphy, echocardiography, laboratory testing, and quality-of-life and SDB
      questionnaires). The primary outcome is the change in the Apnoea-Hypopnoea Index,
      before and after 3 months of treatment. One hundred twenty patients are required
      to detect a significant 20% improvement of the Apnoea-Hypopnoea Index with a
      power of 90% at an alpha risk of 5%. CONCLUSIONS: In the context of the SERVE-HF
      study, physicians are waiting for new trials and alternative therapies. We sought
      to assess in the ENTRESTO-SAS trial whether sacubitril-valsartan could improve
      the outcome of SDB in CHF patients.

PMID- 29469207
TI  - Evaluation of contrasting techniques for X-ray imaging of velvet worms
      (Onychophora).
AB  - Non-invasive imaging techniques like X-ray computed tomography have become very
      popular in zoology, as they allow for simultaneous imaging of the internal and
      external morphology of organisms. Nevertheless, the effect of different staining
      approaches required for this method on samples lacking mineralized tissues, such
      as soft-bodied invertebrates, remains understudied. Herein, we used synchrotron
      radiation-based X-ray micro-computed tomography to compare the effects of
      commonly used contrasting approaches on onychophorans - soft-bodied invertebrates
      important for studying animal evolution. Representatives of Euperipatoides
      rowelli were stained with osmium tetroxide (vapour or solution), ruthenium red,
      phosphotungstic acid, or iodine. Unstained specimens were imaged using both
      standard attenuation-based and differential phase-contrast setups to simulate
      analyses with museum material. Our comparative qualitative analyses of several
      tissue types demonstrate that osmium tetroxide provides the best overall tissue
      contrast in onychophorans, whereas the remaining staining agents rather favour
      the visualisation of specific tissues and/or structures. Quantitative analyses
      using signal-to-noise ratio measurements show that the level of image noise may
      vary according to the staining agent and scanning medium selected. Furthermore,
      box-and-whisker plots revealed substantial overlap in grey values among
      structures in all datasets, suggesting that a combination of semiautomatic and
      manual segmentation of structures is required for comprehensive 3D
      reconstructions of Onychophora, irrespective of the approach selected. Our
      results show that X-ray micro-computed tomography is a promising technique for
      studying onychophorans and, despite the benefits and disadvantages of different
      staining agents for specific tissues/structures, this method retrieves
      informative data that may eventually help address evolutionary questions long
      associated with Onychophora.

PMID- 29469208
TI  - Molecular characterization and multidisciplinary management of Gerbich hemolytic
      disease of the newborn.
AB  - Gerbich (Ge) antigens are high frequency red cell antigens expressed on
      glycophorin C (GYPC) and glycophorin D. Hemolytic disease of the fetus and
      newborn (HDFN) due to Gerbich antibody is rare and presents a clinical challenge,
      as Gerbich negative blood is scarce. We report a case of HDFN due to maternal Ge3
      negative phenotype and anti-Ge3 alloimmunization, successfully managed by
      transfusion of maternal blood. Molecular testing revealed that the mother has
      homozygous deletion of exon 3 of GYPC, the father is homozygous wildtype for
      GYPC, and the infant is obligate heterozygote expressing Ge3.

PMID- 29469209
TI  - The impact of aging on different types of health care: The example of the Polish
      health insurance system.
AB  - The aging phenomenon, which is being observed all over the world, can strongly
      affect health policy and a planning in the health care sector. However, the
      impact of demographic changes on different parts of it can be varied. The main
      objective of this study was to check the possible impact of aging on health
      expenditure (HE) regarding different types of health care and to evaluate whether
      this impact is significant for all analyzed areas. To show a relationship between
      age and HE a special indicator (old-age sensitivity) was defined, showing a
      difference between the standardized value of HE per capita in the age group 65+
      and in the group 20 to 64 (defined as the reference group). Then a simple
      prognosis of expenditure was prepared. Both analyses were done separately for 11
      types of health care services and 2 types of goods reimbursement. The results
      show that while sensitivity varies between the different types of care, however,
      it is strong in most of them. Because of the prognosis, the expenditure will be
      increasing for the 9 types of care and decreasing for 4 of them. While in the
      case of the low values of sensitivity the HE is actually decreasing, the high
      value of sensitivity does not result in a growing tendency. Our main conclusion
      is that it is very important for health policy and planning to take into account
      the diversity of the types of health care and the different influences of changes
      in the size and structure of population on them.

PMID- 29469210
TI  - Refining early-TIPS criteria requires good quality prognostic studies.

PMID- 29469211
TI  - Personalized management of patients with very early hypovascular hepatocellular
      carcinoma.

PMID- 29469212
TI  - Administrative reform and pay-for-performance methods of primary health service
      delivery: A comparison of 3 health districts in Cambodia, 2006-2012.
AB  - Since 1999, performance-based financing or pay-for-performance (P4P) methods have
      been piloted in the Cambodian public health sector, first as one part of external
      contracting approaches with international nongovernment organizations and from
      2009 as a part of internal contracting arrangements between units within the
      Ministry of Health under a wider public sector administrative reform. This study
      analyses these reforms and compares outcomes in 3 health districts. The study
      analysed routine quantitative data for primary care service delivery by using the
      interrupted time series method. Qualitative data were collected from key
      informant interviews. Both the level and the trend line of key service delivery
      indicators during earlier contracting/P4P models were at least maintained and in
      most cases increased with the move to internal contracting. The results of the
      interrupted time series analysis were mixed, mainly due to contextual issues.
      Qualitative results indicated an increased sense of local ownership and financial
      sustainability. Despite the gains, the management of personnel and the
      implementation and the integrity of contract monitoring were found to be
      compromised in this case. To be fully effective, contracting and P4P approaches
      must be accompanied by changes in the structure and culture of government
      administration.

PMID- 29469213
TI  - Exosomes Enter Vaccine Development: Strategies Meeting Global Challenges of
      Emerging Infections.
AB  - New approaches for vaccination must be developed in order to meet the grand
      challenges for emerging infectious diseases. Exosomes now enter vaccine
      development and these are strategies are meeting these global challenges, as
      demonstrated by Anticoli et al., in this issue of Biotechnology Journal. Using
      exosome vaccines has been now been demonstrated in vivo for several viruses such
      as Ebola Virus VP24, VP40, and NP, Influenza Virus NP, Crimean-Congo Hemorrhagic
      Fever NP, West Nile Virus NS3, and Hepatitis C Virus NS3. Now this technology
      must be tested in clinics.

PMID- 29469214
TI  - FOOD NEGLECT AND INFANT DEVELOPMENT.
AB  - The impact of food insecurity on child development in the general U.S. population
      is well-established, yet little is known about the harm of food neglect relative
      to other types of maltreatment. Due to the harmful physiological impact of
      inadequate nutrients and the social impact of food-related stress, it was
      hypothesized that food neglect would be more likely to impair infant cognitive
      and language development than physical abuse, sexual abuse, and other forms of
      neglect. Families of infants (N = 1,951) investigated by Child Protective
      Services were studied using the second cohort of the National Survey of Child and
      Adolescent Well-Being (NSCAW II; NSCAW Research Group, 2002). Results from
      multivariable logistic regression models that controlled for likely confounding
      variables showed that the odds of impairment in cognition and language were
      significantly greater when food neglect was the most serious form of
      maltreatment. Considering that both food insecurity and child neglect are
      associated with poverty and parental mental health problems, it will be important
      for child welfare and mental health professionals to work collaboratively to
      better the health of these vulnerable children.

PMID- 29469215
TI  - Dinitrosyl iron complexes: Formation and antiradical action in heart
      mitochondria.
AB  - Mitochondria are widely known as a major source of reactive oxygen and nitrogen
      species for the cardiovascular system. Numerous studies established that
      superoxide anion radical production by heart mitochondria is only slightly
      suppressed under conditions of deep hypoxia, but is completely blocked under
      anoxia. It was found also that dinitrosyl iron complexes (DNIC) compare
      favourably with other physiologically active derivatives of nitric oxide (NO).
      DNIC with glutathione effectively scavenge superoxide radicals generated by
      mitochondria at different partial pressures of oxygen. Under conditions of
      simulated hypoxia, the synthesis of thiol-containing DNIC takes place in
      mitochondria and is concomitant with a significant decrease in the concentration
      of NO metabolites at the reoxygenation step. Free NO required for DNIC synthesis
      is generated in the reaction of S-nitrosothiols with superoxide or during single
      electron oxidation of the nitroxyl radical (HNO) by coenzyme Q. Plausible
      mechanisms of antiradical effects of DNIC and their protective role in oxidative
      stress induced by hypoxia/reoxygenation of myocardial tissues are considered. (c)
      2018 BioFactors, 44(3):237-244, 2018.

PMID- 29469216
TI  - Total Synthesis of (-)-Enigmazole A.
AB  - Total synthesis of (-)-enigmazole A, a marine macrolide natural product with
      cytotoxic activity, has been accomplished. The tetrahydropyran moiety was
      constructed by means of a domino olefin cross-metathesis/intramolecular oxa
      Michael addition of a delta-hydroxy olefin. After coupling of advanced
      intermediates, the macrocycle was formed through gold-catalyzed rearrangement of
      a propargylic benzoate, followed by ring-closing metathesis of the resultant
      alpha,beta-unsaturated ketone.

PMID- 29469217
TI  - Effect of treatment with direct acting antivirals on body mass index and hepatic
      steatosis in chronic hepatitis C.
AB  - Direct Acting Agents (DAAs) have high cure rate but still lack the knowledge of
      their effect on hepatic steatosis in chronic hepatitis C (CHC). Controlled
      Attenuation Parameter (CAP), evaluated with transient elastography, could help in
      assessment of steatosis grades. We aim to evaluate the effect of DAAs on BMI and
      steatosis in CHC using CAP. This cohort study included 155 CHC Egyptian patients
      divided into three groups according to the DAAs regimens. All patients were
      subjected to pre-treatment and 3-months post-treatment evaluation including BMI,
      laboratory workup and liver stiffness measurement with simultaneous CAP
      determination using the (FibroScan(r)) M probe. Patients mean age was 45.78 +/-
      11.6 years, 60.6% were females, mean BMI 26.63 +/- 2.75 and 18.1% were cirrhotic.
      Baseline assessment revealed no steatosis in 43.9%, 32.9% had mild-moderate
      steatosis and 23.2% had severe steatosis. The overall sustained virological
      response 12 was 93.6%. Follow-up revealed stationary steatosis in 56.7% of
      patients and regression in 21.3%. Mean pre-treatment CAP were significantly lower
      in responders 244.9 +/- 62.4 dB/m versus non-responders; 300 +/-28.4 dB/m (P =
      0.04). ROC curve delineated 273 dB/m as best cutoff for detection of responders
      with an AUC of 0.801, sensitivity 68.2%, and specificity 100%. BMI significantly
      increased after treatment (P = 0.004) particularly in patients with worsened
      steatosis (P = 0.001). Steatosis significantly correlated with BMI (r = 0.3, P
      value = < 0.001). DAAs causes a significant change in steatosis grade in a subset
      of treated patients. Pretreatment CAP was significantly lower in responders. BMI
      significantly increases following treatment particularly in patients with
      worsened steatosis.

PMID- 29469218
TI  - Highly Confined and Tunable Hyperbolic Phonon Polaritons in Van Der Waals
      Semiconducting Transition Metal Oxides.
AB  - 2D van der Waals (vdW) layered polar crystals sustaining phonon polaritons (PhPs)
      have opened up new avenues for fundamental research and optoelectronic
      applications in the mid-infrared to terahertz ranges. To date, 2D vdW crystals
      with PhPs are only experimentally demonstrated in hexagonal boron nitride (hBN)
      slabs. For optoelectronic and active photonic applications, semiconductors with
      tunable charges, finite conductivity, and moderate bandgaps are preferred. Here,
      PhPs are demonstrated with low loss and ultrahigh electromagnetic field
      confinements in semiconducting vdW alpha-MoO3 . The alpha-MoO3 supports strong
      hyperbolic PhPs in the mid-infrared range, with a damping rate as low as 0.08.
      The electromagnetic confinements can reach ~lambda0 /120, which can be tailored
      by altering the thicknesses of the alpha-MoO3 2D flakes. Furthermore, spatial
      control over the PhPs is achieved with a metal-ion-intercalation strategy. The
      results demonstrate alpha-MoO3 as a new platform for studying hyperbolic PhPs
      with tunability, which enable switchable mid-infrared nanophotonic devices.

PMID- 29469219
TI  - Erdheim-Chester disease: description of two illustrative cases involving the
      lung.
AB  - AIM: Erdheim-Chester disease represents a clonal systemic proliferation of
      histiocytes. Bone is the most common site of involvement, although almost any
      organ, including the lungs, can be affected. METHODS AND RESULTS: The diagnosis
      of Erdheim-Chester disease can be difficult, owing to its rarity and protean
      presentation. Correlation between clinical, radiological and histological
      findings is mandatory for identification of the disease. Foamy histiocytes,
      lacking Langerhans cell markers, represent the typical histological findings,
      although their absence does not rule out Erdheim-Chester disease. Identification
      of BRAF mutation can be helpful in making the diagnosis, and allows for the
      development and application of targeted therapies in this setting. CONCLUSIONS:
      Herein, we describe two cases presenting with lung involvement and vertebral
      lesions, lacking the more typical long-bone involvement. One case histologically
      mimicked Rosai-Dorfman disease. However, both cases harboured the pathognomonic
      BRAFV600E mutation.

PMID- 29469220
TI  - Mechanisms in Iodine Catalysis.
AB  - Molecular iodine has been used for more than 100 years as a remarkable catalyst
      for many organic transformations such as cycloadditions, Michael and aldol
      reactions, or esterifications. Different explanations for the origin of its
      catalytic effect have been proposed in the last decades including a "hidden"
      Bronsted acid catalysis by HI, a Lewis-acid (or halogen-bond) activation, or
      catalysis by an iodonium(I) species. Recently, iodine catalysis again gained more
      interest due to the latest developments in halogen-bond catalysis. In this
      Minireview, we first summarize the experimental basis for the proposed modes of
      activation. Subsequently, we analyze typical iodine-catalyzed reactions to gain
      more insights into the underlying reaction mechanisms.

PMID- 29469221
TI  - Molecular Recognition by a Short Partial Peptide of the Adrenergic Receptor: A
      Bottom-Up Approach.
AB  - Receptor-neurotransmitter molecular recognition is key for neurotransmission.
      Although crystal structures of the receptors are known, the mechanism for
      recognition is not clear. Reported here is the ultraviolet (UV) and infrared (IR)
      spectra of complexes between a partial peptide (SIVSF), mimicking the binding
      motif of a catechol ring in the adrenergic receptor, and various ligands. The UV
      spectra show that two isomers coexist in the complex of SIVSF with properly
      recognized ligands, such as protonated adrenaline (adrenalineH+ ). From IR
      spectra, they are assigned to catechol- and amino-bound structures. The catechol
      bound structure is not observed when the ligand is replaced by nonproper
      molecules, such as noradrenalineH+ . The results suggest that SIVSF not only
      recognizes the catechol ring but can distinguish differences in the amine side
      chain. The method provides a new possibility for screening molecules as potential
      therapeutics for activating the receptor.

PMID- 29469224
TI  - Anisotropic Colloids: From Non-Templated to Patchy Templated Synthesis.
AB  - Self-assembly of colloidal particles is an important and challenging way to
      generate novel colloidal superstructures for new materials. Recent progress on
      syntheses of anisotropic colloids highlights opportunities for such self
      assembly, particularly in defining new non-cubic superstructures. Both non
      templated and templated synthesis play an important role in preparing anisotropic
      colloidal particles. In this article, we briefly summarize recent progress in
      anisotropic colloids by non-templated and conventional templated synthesis, and
      introduce a conceptual strategy of "patchy templated synthesis" that differs from
      the conventional approach. We illustrate this strategy with recent examples
      emanating from colloidal rings, and discuss the future opportunities with this
      strategy for the synthesis of other anisotropic colloids.

PMID- 29469223
TI  - Mitoprotective therapy preserves chondrocyte viability and prevents cartilage
      degeneration in an ex vivo model of posttraumatic osteoarthritis.
AB  - : No disease-modifying osteoarthritis (OA) drugs are available to prevent
      posttraumatic osteoarthritis (PTOA). Mitochondria (MT) mediate the pathogenesis
      of many degenerative diseases, and recent evidence indicates that MT dysfunction
      is a peracute (within minutes to hours) response of cartilage to mechanical
      injury. The goal of this study was to investigate cardiolipin-targeted
      mitoprotection as a new strategy to prevent chondrocyte death and cartilage
      degeneration after injury. Cartilage was harvested from bovine knee joints and
      subjected to a single, rapid impact injury (24.0 +/-1.4 MPa, 53.8 +/- 5.3 GPa/s).
      Explants were then treated with a mitoprotective peptide, SS-31 (1uM),
      immediately post-impact, or at 1, 6, or 12 h after injury, and then cultured for
      up to 7 days. Chondrocyte viability and apoptosis were quantified in situ using
      confocal microscopy. Cell membrane damage (lactate dehydrogenase activity) and
      cartilage matrix degradation (glycosaminoglycan loss) were quantified in
      cartilage-conditioned media. SS-31 treatment at all time points after impact
      resulted in chondrocyte viability similar to that of un-injured controls. This
      effect was sustained for up to a week in culture. Further, SS-31 prevented impact
      induced chondrocyte apoptosis, cell membrane damage, and cartilage matrix
      degeneration. CLINICAL SIGNIFICANCE: This study is the first investigation of
      cardiolipin-targeted mitoprotective therapy in cartilage. These results suggest
      that even when treatment is delayed by up to 12 h after injury, mitoprotection
      may be a useful strategy in the prevention of PTOA. (c) 2018 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-10, 2018.

PMID- 29469222
TI  - Borrelia burgdorferi Infection and Lyme Disease in North American Horses: A
      Consensus Statement.
AB  - Borrelia burgdorferi infection is common in horses living in Lyme endemic areas
      and the geographic range for exposure is increasing. Morbidity after B.
      burgdorferi infection in horses is unknown. Documented, naturally occurring
      syndromes attributed to B. burgdorferi infection in horses include
      neuroborreliosis, uveitis, and cutaneous pseudolymphoma. Although other clinical
      signs such as lameness and stiffness are reported in horses, these are often not
      well documented. Diagnosis of Lyme disease is based on exposure to B.
      burgdorferi, cytology or histopathology of infected fluid or tissue and antigen
      detection. Treatment of Lyme disease in horses is similar to treatment of humans
      or small animals but treatment success might not be the same because of species
      differences in antimicrobial bioavailability and duration of infection before
      initiation of treatment. There are no approved equine label Lyme vaccines but
      there is strong evidence that proper vaccination could prevent infection in
      horses.

PMID- 29469225
TI  - Successful hematopoietic stem cell transplantation for osteopetrosis using
      reduced intensity conditioning.
AB  - BACKGROUND: Infantile malignant osteopetrosis (IMO) is an autosomal recessive
      condition characterized by defective osteoclast activity, with hematopoietic bone
      marrow transplant being the only available cure. Over the past several years, new
      conditioning regimes and donor options have emerged, thus extending the
      possibility of cure to a greater number of patients and improving the outcomes of
      bone marrow transplant. Here we detail the outcomes of bone marrow transplant in
      a cohort of 31 patients treated with a combination of fludarabine, treosulphan,
      thiotepa, and antithymocyte globulin. PROCEDURES: Thirty-one patients with IMO
      who underwent hematopoietic stem cell transplantation with fludarabine,
      treosulphan, thiotepa, and antithymocyte globulin at our center from 2012 to 2017
      are retrospectively reviewed in this study. Twenty-six patients were transplanted
      from 10/10 matched donors (13 from siblings, 11 from unrelated, and two from
      extended family donors), four from 9/10 matched unrelated donors, and one from a
      9/10 matched family donor. RESULTS: Overall survival was 100% with a median
      follow-up of 363 days (range 74-1891). There were 12 cases of acute graft versus
      host disease (GvHD) (38.7%), no cases of veno-occlusive disease, and eight cases
      of hypercalcemia (25.8%). Almost 80% of patients suffered viral reactivations
      with two cases of Epstein-Barr-virus-driven post-transplant lymphoproliferative
      disease. All cases of GvHD and viral reactivation were successfully treated.
      CONCLUSIONS: We conclude that transplantation in children with IMO using
      fludarabine, treosulphan, thiotepa, and antithymocyte globulin is safe and
      effective and should be performed as early as possible following diagnosis, prior
      to the development of severe disease sequelae.

PMID- 29469226
TI  - Covalent Functionalization of Black Phosphorus with Conjugated Polymer for
      Information Storage.
AB  - Major disadvantages of black phosphorus (BP) are its poor air-stability and poor
      solubility in common organic solvents. The best way to solve this problem is to
      incorporate BP into a polymer backbone or a polymer matrix to form novel
      functional materials that can provide both challenges and opportunities for new
      innovation in optoelectronic and photonic applications. As a proof-of concept
      application, we synthesized in situ the first highly soluble conjugated polymer
      covalently functionalized BP derivative (PDDF-g-BP) which was used to fabricate a
      resistive random access memory (RRAM) device with a configuration of Au/PDDF-g
      BP/ITO. In contrast to PDDF without memory effect, PDDF-g-BP-based device
      exhibits a nonvolatile rewritable memory performance, with a turn-on and turn-off
      voltages of +1.95 V and -2.34 V, and an ON/OFF current ratio of 104 . The current
      through the device in both the ON and OFF states is still kept unchanged even at
      200th switching cycle. The PDDF/BP blends show a very unstable memory performance
      with a very small ON/OFF current ratio.

PMID- 29469227
TI  - Auxin signalling of Arachis hypogaea activated by colonization of mutualistic
      fungus Phomopsis liquidambari enhances nodulation and N2 -fixation.
AB  - Beneficial fungal and rhizobial symbioses share commonalities in phytohormones
      responses, especially in auxin signalling. Mutualistic fungus Phomopsis
      liquidambari effectively increases symbiotic efficiency of legume peanut (Arachis
      hypogaea L.) with another microsymbiont, bradyrhizobium, but the underlying
      mechanisms are not well understood. We quantified and manipulated the IAA
      accumulation in ternary P. liquidambari-peanut-bradyrhizobial interactions to
      uncover its role between distinct symbioses. We found that auxin signalling is
      both locally and systemically induced by the colonization of P. liquidambari with
      peanut and further confirmed by Arabidopsis harbouring auxin-responsive reporter,
      DR5:GUS, and that auxin action, including auxin transport, is required to
      maintain fungal symbiotic behaviours and beneficial traits of plant during the
      symbiosis. Complementation and action inhibition experiments reveal that auxin
      signalling is involved in P. liquidambari-mediated nodule development and N2 
      fixation enhancement and symbiotic gene activation. Further analyses showed that
      blocking of auxin action compromised the P. liquidambari-induced nodule phenotype
      and physiology changes, including vascular bundle development, symbiosome and
      bacteroids density, and malate concentrations, while induced the accumulation of
      starch granules in P. liquidambari-inoculated nodules. Collectively, our study
      demonstrated that auxin signalling activated by P. liquidambari symbiosis is
      recruited by peanut for bradyrhizobial symbiosis via symbiotic signalling pathway
      activation and nodule carbon metabolism enhancement.

PMID- 29469228
TI  - Proteomic Studies on the Swim Bladder of the European Eel (Anguilla anguilla).
AB  - The swim bladder of a fish is a vital organ that with gas gland cells in the swim
      bladder wall enables key physiological functions including buoyancy regulation in
      the face of different hydrostatic pressures. Specific gas gland cells produce and
      secrete acidic metabolites into the blood in order to reduce the physical
      solubility of gases and blood gas transport capacity for regulating the volume of
      the swim bladder. Transcriptomic analyses have provided evidence at the RNA level
      but no specific studies at the protein level have been carried out so far.
      Herein, it was the aim of the study to show swim bladder proteins of the yellow
      stage European eel by label-free LCMS (Q-Exactive Plus) that resulted in the
      identification of 6223 protein groups. Neurotransmitter receptors and
      transporters were enriched in the membrane fraction and enzymes for acid
      production were observed. The list of identified proteins may represent a useful
      tool for further proteomics experiments on this organ. All MS proteomics data are
      available at the PRIDE repository with the dataset identifier PXD007850.

PMID- 29469229
TI  - Hypolipidemic and Antioxidant Properties of Oryzanol Concentrate in Reducing
      Diabetic Nephropathy via SREBP1 Downregulation Rather than beta-Oxidation.
AB  - SCOPE: Diabetic nephropathy (DN) is a micro-vascular complication of chronic
      diabetes. Sterol regulatory element binding protein1 (SREBP1) participation in
      the development of DN is reported. Oryzanol concentrate (OC) at 0.1% and 0.3% is
      tested for its antioxidant and hypolipidemic effects. The aim of the work is to
      study the involvement of OC in the amelioration of DN in STZ-induced diabetic
      animal model. METHODS AND RESULTS: Animals were grouped into starch, high-fat,
      and OC-treated control/diabetic groups (SFC/SFD, HFC/HFD, OFC/OFD). The markers
      of DN, increased glomerular filtration rate and kidney weight, were evident in
      HFD and reduced in OFD group by ~1.09 and ~1.3 fold, respectively. The
      amelioration of defensive antioxidant enzyme activities and lipid peroxidation,
      expressions of lipid-associated biomolecules (SREBP1 and FAS) were also observed.
      HFD showed increased ECM accumulation of glycoproteins, particularly Type IV
      collagen, fibronectin. SREBP1-associated gene transforming growth factor-beta
      (TGF-beta) was reduced on treatment (OFD ~ 1.3 fold) as to HFD (~2.7 fold).
      CONCLUSION: Oryzanol concentrate, having hypolipidemic and antioxidant
      properties, also downregulated the lipid biosynthesis through reduced SREBP1-TGF
      beta interactions (EMSA) and could effectively ameliorate DN. Gene (ACC2, Cpt1,
      and ACOX) expression studies showed that beta-oxidation was not involved in
      reducing DN.

PMID- 29469230
TI  - Quantitative 3D imaging of cell level auxin and cytokinin response ratios in
      soybean roots and nodules.
AB  - Legume-Rhizobium symbiosis results in root nodules where rhizobia fix atmospheric
      nitrogen into plant usable forms in exchange for plant-derived carbohydrates. The
      development of these specialized root organs involves a set of carefully
      orchestrated plant hormone signalling. In particular, a spatio-temporal balance
      between auxin and cytokinin appears to be crucial for proper nodule development.
      We put together a construct that carried nuclear localized fluorescence sensors
      for auxin and cytokinin and used two photon induced fluorescence microscopy for
      concurrent quantitative 3-dimensional imaging to determine cellular level auxin
      and cytokinin outputs and ratios in root and nodule tissues of soybean. The use
      of nuclear localization signals on the markers and nuclei segmentation during
      image processing enabled accurate monitoring of outputs in 3D image volumes. The
      ratiometric method used here largely compensates for variations in individual
      outputs due to sample turbidity and scattering, an inherent issue when imaging
      thick root and nodule samples typical of many legumes. Overlays of determined
      auxin/cytokinin ratios on specific root zones and cell types accurately reflected
      those predicted based on previously reported outputs for each hormone
      individually. Importantly, distinct auxin/cytokinin ratios corresponded to
      distinct nodule cell types indicating a key role for these hormones in nodule
      cell type identity.

PMID- 29469231
TI  - Rational Tuning of Fluorobenzene Probes for Cysteine-Selective Protein
      Modification.
AB  - Fluorobenzene probes for protein profiling through selective cysteine labeling
      have been developed by rational reactivity tuning. Tuning was achieved by
      selecting an electron-withdrawing para substituent in combination with variation
      of the number of fluorine substituents. Optimized probes chemoselectively
      arylated cysteine residues in proteins under aqueous conditions. Probes linked to
      azide, biotin, or a fluorophore were applicable to labeling of eGFP and albumin.
      Selective inhibition of cysteine proteases was also demonstrated with the probes.
      Additionally, probes were tuned for site-selective labeling of cysteine residues
      and for activity-based protein profiling in cell lysates.

PMID- 29469232
TI  - Gastrointestinal: A rare case of concomitant type III achalasia and chronic
      idiopathic intestinal pseudo-obstruction.

PMID- 29469233
TI  - Hepatobiliary and Pancreatic: A rare form of autoimmune pancreatitis mimicking
      mixed-type intraductal papillary mucinous neoplasm.

PMID- 29469234
TI  - Gastrointestinal: Improvement of refractory oral ulcer of Behcet's disease after
      eradication of Helicobacter pylori.

PMID- 29469235
TI  - Hepatobiliary and Pancreatic: A black liver of Dubin-Johnson syndrome.

PMID- 29469236
TI  - Gastrointestinal: Tracheoesophageal fistula secondary to pressure necrosis from
      tracheostomy tube balloon cuff.

PMID- 29469237
TI  - Determination of 15 polycyclic aromatic hydrocarbons in aquatic products by solid
      phase extraction and GC-MS.
AB  - We propose a method for the simultaneous determination of 15 kinds of polycyclic
      aromatic hydrocarbons in marine samples (muscle) employing gas chromatography
      with mass spectrometry after saponification with ultrasound-assisted extraction
      and solid-phase extraction. The experimental conditions were optimized by the
      response surface method. In addition, the effects of different lyes and
      extractants on polycyclic aromatic hydrocarbons extraction were discussed, and
      saturated sodium carbonate was first used as the primary saponification reaction
      and extracted with 10 mL of ethyl acetate and secondly 1 mol/L of sodium
      hydroxide and 10 mL of n-hexane were used to achieve better results. The average
      recovery was 67-112%. Satisfactory data showed that the method has good
      reproducibility with a relative standard deviation of <13%. The detection limits
      of polycyclic aromatic hydrocarbons were 0.02-0.13 ng/g. Compared with other
      methods, this method has the advantages of simple pretreatment, low solvent
      consumption, maximum polycyclic aromatic hydrocarbons extraction, the fast
      separation speed, and the high extraction efficiency. It is concluded that this
      method meets the batch processing requirements of the sample and can also be used
      to determine polycyclic aromatic hydrocarbons in other high-fat (fish, shrimp,
      crab, shellfish) biological samples.

PMID- 29469238
TI  - Fire-Retardant and Thermally Insulating Phenolic-Silica Aerogels.
AB  - Energy efficient buildings require materials with a low thermal conductivity and
      a high fire resistance. Traditional organic insulation materials are limited by
      their poor fire resistance and inorganic insulation materials are either brittle
      or display a high thermal conductivity. Herein we report a mechanically resilient
      organic/inorganic composite aerogel with a thermal conductivity significantly
      lower than expanded polystyrene and excellent fire resistance. Co-polymerization
      and nanoscale phase separation of the phenol-formaldehyde-resin (PFR) and silica
      generate a binary network with domain sizes below 20 nm. The PFR/SiO2 aerogel can
      resist a high-temperature flame without disintegration and prevents the
      temperature on the non-exposed side from increasing above the temperature
      critical for the collapse of reinforced concrete structures.

PMID- 29469239
TI  - Compulsive Sexual Behaviors Treated With Naltrexone Monotherapy.

PMID- 29469240
TI  - Actual Versus Expected Doses of Half Tablets Containing Prescribed Psychoactive
      Substances: A Systematic Review.
AB  - Objective: To assess through a systematic review of the literature if the
      practice of splitting tablets containing psychoactive/psychotropic medications
      for medical or economic reasons would result in the expected doses. Data Sources:
      A MEDLINE and PsycInfo comprehensive search of English-language publications from
      January 1999 to December 2015 was conducted using the terms describing tablet
      splitting (tablet splitting, split tablets, tablet subdivision, divided tablets,
      and half tablets) and psychoactive substances (psychoactive medicines,
      psychotropic medicines, antidepressants, anxiolytics, anticonvulsants,
      antipsychotics, and antiparkinsonian agents). An additional supplementary search
      included the references from the articles found. Study Selection/Data Extraction:
      Studies were included if splitting content was directly related to psychoactive
      medications and examined the effect of tablet splitting on drug uniformity,
      weight uniformity, and adherence of psychoactive drugs. Articles were
      systematically reviewed and examined regarding the study design, methodology, and
      results of the study. A total of 125 articles were screened, and 13 were
      selected. Results: Tablet splitting implications are extensive, yet substantial
      deviations from the ideal weight, potency, and dose uniformity are more prone to
      be important to patient safety. The uneven division of tablets might result in
      the administration of different doses than what was prescribed, causing under- or
      overdosing, which might be relevant depending on the drug. In 55% of the cases,
      splitting psychoactive drugs was satisfactory. Conclusions: It cannot be
      generalized that splitting psychoactive drugs compromises dose accuracy, thus
      tablet splitting might still be employed in cases in which the advantages
      outweigh the disadvantages. It is recommended that alternatives be adopted to
      prevent the disadvantages related to tablet splitting.

PMID- 29469241
TI  - Dealing With a Patient Who Has Given Up.

PMID- 29469242
TI  - A 5-Year Follow-Up of Psychological Distress Caused by the Fukushima Daiichi
      Nuclear Power Plant Accident: A Case Report.

PMID- 29469243
TI  - Vilazodone-Induced Decrease in Libido: A Case Report.

PMID- 29469244
TI  - Longitudinal Associations of Explosive and Adventurous Temperament Profiles With
      Character Development: The Modifying Effects of Social Support and Attachment.
AB  - OBJECTIVE: The aim of this study was to examine (a) whether adventurous and
      explosive temperament profiles (presumed precursors of antisocial and borderline
      personality) are associated with character traits over a 15-year follow-up and
      (b) whether social support and attachment security modify the relationship
      between temperament profiles and character development. METHODS: 2,028 subjects
      of the Young Finns study completed the Temperament and Character Inventory, the
      Multidimensional Scale of Perceived Social Support, and the Relationship
      Questionnaire at 3 assessment points between 1997 and 2012. RESULTS: Both
      explosive and adventurous temperament profiles seemed to predispose individuals
      to have less mature personalities; that is, these profiles were consistently
      associated with lower cooperativeness (P < .001), and explosive temperament also
      with lower self-directedness (P < .001), over the entire follow-up period. These
      relationships did not vary significantly at the individual level and were
      sustained after controlling for age, gender, and socioeconomic status. However,
      the presence of high social support and secure attachment was found to decrease
      the likelihood that explosive temperament would lead to an immature adulthood
      character (P < .001). In contrast, persons with the adventurous temperament were
      likely to have a more mature character under low social support and an immature
      one under high experienced social support (P < .05). CONCLUSIONS: Individuals
      with the explosive temperament benefit from high social support and secure
      attachment. From the point of view of the therapy process, this knowledge might
      be of importance. In contrast, individuals with the adventurous temperament were
      able to direct their behavior better in social environments that were not likely
      to support their basic temperaments.

PMID- 29469246
TI  - Reflective practices: meaningful recognition for healthy work environments.
AB  - Nurses' decisions about their intent to remain in the workforce are based on
      various factors. A healthy work environment in which work done well is recognised
      and appreciated contributes to nurses' satisfaction and better patient outcomes.
      This article examines the American Association of Critical-Care Nurses framework
      for a healthy work environment, focusing on standards for meaningful recognition.
      Reflective practice, which provides a self-analytical approach to appreciate and
      value one's work, is viewed as self-recognition. Neither boastful nor arrogant,
      reflective self-recognition is part of progression to professional maturity. It
      involves examining events at work continuously and systematically to learn,
      appreciate and move to higher levels of contribution in the workplace.

PMID- 29469245
TI  - Antipsychotic Prescriptions Among Adults With Major Depressive Disorder in Office
      Based Outpatient Settings: National Trends From 2006 to 2015.
AB  - OBJECTIVE: A recent moderately long-term study found an antipsychotic to be more
      effective than an antidepressant as the next-step treatment of unresponsive major
      depressive disorder (MDD). It is thus timely to examine recent trends in the
      pharmacoepidemiology of antipsychotic treatment of MDD. METHODS: Data from the
      2006-2015 National Ambulatory Medical Care Survey, nationally representative
      samples of office-based outpatient visits in adults with MDD (ICD-9-CM codes
      296.20-296.26 and 296.30-296.36) (n = 4,044 unweighted), were used to estimate
      rates of antipsychotic prescribing over these 10 years. Multivariable logistic
      regression analysis identified demographic and clinical factors independently
      associated with antipsychotic use in MDD. RESULTS: Antipsychotic prescribing for
      MDD increased from 18.5% in 2006-2007 to 24.9% in 2008-2009 and then declined to
      18.9% in 2014-2015. Visits with adults 75 years or older showed the greatest
      decline from 27.0% in 2006-2007 to 10.7% in 2014-2015 (OR for overall trend =
      0.73; 95% CI, 0.56-0.95). The most commonly prescribed antipsychotic agents were
      aripiprazole, olanzapine, quetiapine, and risperidone. Antipsychotic prescription
      was associated with being black or Hispanic, having Medicare among adults under
      65 years or Medicaid as a primary source of payment, and receiving mental health
      counseling, 3 or more concomitant medications, and diagnosis of cannabis use
      disorder (P < .01). CONCLUSIONS: Antipsychotics, prescribed for about one-fifth
      of adults with MDD, increased and then declined from 2006 to 2015, reflecting,
      first, FDA approval and then concern about adverse effects in the elderly. Future
      research should track evolving trends following the publication of evidence of
      greater long-term effectiveness of antipsychotic than antidepressant next-step
      therapy in adults with MDD.

PMID- 29469247
TI  - High fidelity simulation to improve multidisciplinary team working with pre
      registrants.
AB  - Simulation has been introduced in recent years into international nursing
      curricula. Many educational establishments have developed simulation centres that
      resemble the ward settings nursing students will be exposed to so that they can
      use the same equipment as they will in clinical practice. This is referred to as
      high fidelity simulation training (HFST). This article reflects on an example of
      a multidisciplinary HFST scenario in the context of the assessment and
      accountability and learning domains of the Nursing and Midwifery Council
      standards. The article also discusses the assessment, feedback and evaluation
      process.

PMID- 29469248
TI  - [Endemic status of schistosomiasis in People's Republic of China in 2015].
AB  - This report presented the endemic status of schistosomiasis in the People's
      Republic of China at a national level in 2015, and analyzed the data collected
      from the national schistosomiasis prevention and control system and 457 national
      schistosomiasis surveillance sites. Among the 12 provinces (municipality,
      autonomous region) endemic for schistosomiasis japonica in P. R. China, 5
      provinces (municipality, autonomous region), i.e., Shanghai, Zhejiang, Fujian,
      Guangdong and Guangxi, had achieved transmission interruption, and 7 provinces of
      Sichuan, Yunnan, Jiangsu, Hubei, Anhui, Jiangxi and Hunan had achieved
      transmission control by the end of 2015. There were 453 endemic counties (city,
      district) covering 252 million people, specifically including 29 980 endemic
      villages of 68.61 million people at risk of infection. Among the 453 endemic
      counties (city, district), 75.72% (343/453) and 24.28% (110/453) reached the
      criteria of transmission interruption and transmission control, respectively. By
      the end of 2015, it was estimated of 77 194 cases of schistosomiasis, which were
      decreased by 33.23% compared with 115 614 cases in 2014. No acute schistosomiasis
      cases were reported in 2015. There were 30 843 advanced schistosomiasis cases
      documented in 2015. A total of 8 736 036 individuals received schistosomiasis
      examinations and 3 606 individuals were parasitologically diagnosed, which were
      decreased by 56.40% compared with 8 270 cases in 2014. An Oncomelania hupensis
      snail survey was performed in 19 965 endemic villages and the snails were found
      in 5 609 villages, accounting for 28.09% of total villages, with 31 newly
      detected villages with snails. The snail survey covered an area of 593 572.66 hm2
      and snails were found in an area of 173 462.50 hm2, including a newly detected
      area of 666.04 hm2. No infected snails were found in 2015. A total of 879 373
      bovines were raised in the schistosomiasis endemic regions. Of them, 526 062
      bovines received stool examinations, resulting in 315 infected bovines. There
      were 170 438 schistosomiasis cases receiving drug treatment in 2015, with 2 449
      696 individuals undergoing expanded chemotherapy. There were 318 bovines with
      schistosomiasis receiving drug treatment, with 483 213 bovines undergoing
      expanded chemotherapy. A total of 144 305.52 hm2 area was subject to snail
      control by using molluscicides, with an actual molluscicide-treated area of 69
      221.57 hm2, and 4 572.06 hm2 snail habitats were treated by environmental
      modification. Based on the data from the 457 national schistosomiasis
      surveillance sites, the mean Schistosoma japonicum infection rate was 0.05% and
      0.04% in humans and bovines, respectively. No infected snails were found in all
      the surveillance sites. The results demonstrate a decline in the endemicity of
      schistosomiasis in P. R. China and the country reached the criteria of
      transmission control at the national level. However, the endemic situation of
      schistosomiasis is unstable in some regions with newly-reached transmission
      control, and further control and effective surveillance should be strengthened to
      consolidate the achievements and reduce the endemic situation of schistosomiasis
      in P. R. China.

PMID- 29469249
TI  - [Impact of schistosomiasis transmission by catastrophic flood damage and
      emergency response in China].
AB  - Flood damage is one of the ordinary natural calamities. The areas of middle and
      down of the Yangtze River and its south are the endemic area of schistosomiasis.
      As the flood damage, it causes property loss, and harm public and people health
      severely even. This paper aims at the status of catastrophic flood damage again
      in the Yangtze River basin, analyzes the impact of schistosomiasis transmission
      by it, and indicates that at present, the process of schistosomiasis control in
      China is marching from transmission control to transmission interruption and
      elimination, but the frequent flooding exacerbates Oncomelania hupensis snail
      breeding area and schistosomiasis source spreading, which may influence, in a
      certain extent, the realization of the goal of schistosomiasis control in China.
      We should timely assess and monitor the impact and risk of schistosomiasis
      transmission by flood damage, and give the early warning and adopt emergency
      handling measures in time. This paper also proposes the disaster prevention
      measures according to flood damage stages (the early, middle, later, and post
      flood) and the occurrence and development of damage and endemic situation, so as
      to control the risk and damage of the disease transmission in a high limit, to
      consolidate the current achievements of schistosomiasis prevention and control
      and guarantee the realization of the goal of schistosomiasis interruption and
      elimination in China on the schedule.

PMID- 29469250
TI  - [Pattern analysis of tempo-spatial distribution of schistosomiasis in marshland
      epidemic areas in stage of transmission control].
AB  - OBJECTIVE: To investigate the tempo-spatial patterns of schistosomiasis in
      Jiangling County, Hubei Province, so as to identify the risk areas and provide
      the scientific evidence in following intervention plans for marshland epidemic
      areas in the stage of transmission control. METHODS: The schistosomiasis
      epidemiological data in Jiangling County from 2009 to 2013 together with the
      related geographical information were collected and analyzed. The tempo-spatial
      distribution patterns were analyzed by the spatial autocorrelation analysis and
      spatial clustering analysis. RESULTS: The human infection rate was decreased from
      2.15% in 2009 to 0.63% in 2013, which was the historically low level. The results
      of tempo-spatial analysis showed that there were spatial clustering effects in
      human schistosomiasis infection for each of the years. The values of spatial
      autocorrelation index Moran's I were statistically significant. Eighteen and
      thirty-five clusters were detected by using SatScan and FlexScan software,
      respectively. CONCLUSIONS: From 2009 to 2013, the schistosomiasis endemic
      situation in Jiangling County presented a decline trend and reached the
      historical low level. The identified spatial clustering areas should be targeted
      as the prioritized areas for schistosomiasis control.

PMID- 29469251
TI  - [Prediction of schistosomiasis infection rates of population based on ARIMA-NARNN
      model].
AB  - OBJECTIVE: To explore the effect of the autoregressive integrated moving average
      model-nonlinear auto-regressive neural network (ARIMA-NARNN) model on predicting
      schistosomiasis infection rates of population. METHODS: The ARIMA model, NARNN
      model and ARIMA-NARNN model were established based on monthly schistosomiasis
      infection rates from January 2005 to February 2015 in Jiangsu Province, China.
      The fitting and prediction performances of the three models were compared.
      RESULTS: Compared to the ARIMA model and NARNN model, the mean square error
      (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of the
      ARIMA-NARNN model were the least with the values of 0.011 1, 0.090 0 and 0.282 4,
      respectively. CONCLUSIONS: The ARIMA-NARNN model could effectively fit and
      predict schistosomiasis infection rates of population, which might have a great
      application value for the prevention and control of schistosomiasis.

PMID- 29469252
TI  - [Grey relational analysis of environment interference factors and control
      measures on endemic status of schistosomiasis in Poyang Lake Eco-economic
      Region].
AB  - OBJECTIVE: To explore the impact of environment factors and social economic
      factors (environment interference factors for short) and control measures on the
      endemic status of schistosomiasis in Poyang Lake Eco-economic Region. METHODS:
      The grey relational analysis model was applied to analyze the relationships
      between the key indexes of schistosomiasis epidemic status and the environment
      interference factors and control measures in Jiujiang City of Poyang Lake Eco
      economic Region. RESULTS: Six environment factors, which included the annual
      average water level of Poyang Lake, average annual temperature, storm frequency,
      annual average relative humidity, annual sunshine duration, and annual
      precipitation, had the most closed relationship with the indexes of
      schistosomiasis epidemic status (all ri > 0.9). Among the socioeconomic factors,
      the number of health technicians and beds of health facilities were most
      associated with the indexes of schistosomiasis epidemic status. Among the control
      measures of schistosomiasis, the number of cattle treated with extending
      chemotherapy, chemically killing of Oncomelania hupensis snails and eco
      renovation were most associated with the indexes of schistosomiasis epidemic
      status. CONCLUSIONS: The various environment interference factors and their
      interaction should be considered in formulating the comprehensive control
      strategy for schistosomiasis, and the control strategy should be adjusted
      according to the epidemic dynamic and schistosomiasis-focused targets, so as to
      further strengthen the scientificity and validity of the control strategy.

PMID- 29469253
TI  - [Study on cut-off value of IHA method for schistosomiasis diagnosis in different
      endemic areas].
AB  - OBJECTIVE: To explore the cut-off value of the indirect haemagglutination test
      (IHA) method for schistosomiasis japonica diagnosis in different endemic areas.
      METHODS: Totally 55 nature villages of the lake-type endemic counties, Yugan and
      Xinzi, in Poyang Lake Region of Jiangxi Province were chosen as the study fields,
      and all the villagers over 5 years old were parallelly examined by Kato-Katz
      method + miracidial hatching test and IHA method. The detection data were
      analyzed by the correlation analysis, and the threshold values of the IHA method
      in different endemic areas were decided by the receiver operating characteristic
      (ROC) curve. RESULTS: The positive rate of stool examinations of the villagers
      was correlated with the distribution trend of the antibody level of whole
      population (r = 0.588, P < 0.05), but no correlation with the antibody level of
      the positive population (r = 0.221, P > 0.05). The antibody level of stool
      negative population during the period of 2008 to 2011 detected by IHA method
      dropped year by year, and the annual difference was statistically significant (F
      = 3.650, P < 0.05). While the antibody level of stool-positive population found
      during the period of 2008 to 2011 maintained a certain high level in the 4 years,
      and there was no statistically significant difference among them (F = 2.461, P >
      0.05). When the positive rates were <1%, 1%-5% or >5%, the specificity of
      diagnosis could be improved when 1?80, 1?20 and 1?10 were used as the cut-off
      values of IHA correspondingly. CONCLUSIONS: The different threshold values for
      diagnosis of schistosomiasis japonica should be considered while using IHA method
      to screen out patients in different endemic areas.

PMID- 29469254
TI  - [Study on interventions based on systematic ecological system construction to
      interrupt transmission of schistosomiasis in hilly endemic regions].
AB  - OBJECTIVE: To study the effectiveness of comprehensive control measures based on
      systematic ecological system construction to interrupt the transmission of
      schistosomiasis in hilly endemic regions in Sichuan Province, so as to provide
      the evidence for adjustment of schistosomiasis prevention and control strategies.
      METHODS: A high endemic area of schistosomiasis, Panao Township of Dongpo
      District in Meishan City, was selected as a demonstration area. The comprehensive
      measures for schistosomiasis control with focus on systematic ecological
      management were implemented, and the income of residents, indexes of
      schistosomiasis control effect and so on were investigated before and after the
      intervention and the results were compared. RESULTS: The project based on
      systematic ecological system construction started in 2009 and 317.351 million
      Yuan was put into the construction. The construction included economic forest
      plant base (1 866.68 hm2, 72.66% of the total farmland areas), ecological
      protection gardens (585.35 hm2) and so on. Totally 97.04% of historical areas
      with Oncomelania hupensis snails were comprehensively improved. In 2015, the
      peasants' pure income per capita increased 4 938 Yuan, with the average annual
      growth rate of 14.69%. All the farm cattle were replaced by the machine. The
      benefit rate of water improvement was increased by 52.84% and the coverage rate
      of harmless toilets increased by 18.30%. The positive rate of serological tests
      for schistosomiasis decreased from 7.69% to 3.50%, and the positive rate of
      parasitological tests decreased from 1.18% to 0. The area with snails was
      decreased from 23.33 hm2 to 0. The awareness rate of schistosomiasis control
      knowledge and correct behavior rate of the residents increased from 85.50% and
      82.60% to 95.70% and 93.90% respectively. CONCLUSIONS: The comprehensive
      schistosomiasis control measures based on systematic ecological management are
      conform to the currently actual schistosomiasis prevention and control work in
      hilly endemic regions, and have good ecological economic benefit and
      schistosomiasis control effectiveness, which provide an effectively new model of
      prevention and control for advancing process, consolidating the effect, finally
      realizing goal of interruption and elimination of schistosomiasis in hilly
      endemic regions.

PMID- 29469255
TI  - [Analysis of channels of going abroad of imported malaria patients in Jiangsu
      Province, China].
AB  - OBJECTIVE: To analyze the channels of going abroad of imported malaria patients
      in Jiangsu Province, so as to provide the evidence for the control of imported
      malaria and health intervention for high-risk population. METHODS: The data of
      imported malaria cases in Jiangsu Province in 2015 were collected and the
      channels of going abroad were analyzed. The Quantum GIS 1.7.4 software was
      applied to map. RESULTS: Totally 405 imported cases were reported in Jiangsu
      Province in 2015, and the cases increased by 14.1% compared with those in 2014.
      All the patients were migrant workers. The migrant workers were mostly sent
      abroad by construction companies [43.21% (175/405)]. The dispatching companies
      were mainly concentrated in Taizhou, Lianyungang, Zhenjiang and Yangzhou cities,
      accounting for 6.17% (25/405), 3.21% (13/405), 2.72% (11/405) and 2.22% (9/405),
      respectively. Totally 176 (43.46%) patients returned to China having accompanied
      workers, and 1.21% (9/745) of accompanied workers were found having symptoms of
      malaria later. CONCLUSIONS: It is difficult to monitor malaria in overseas
      migrant works in Jiangsu Province. The channels of going abroad of migrant
      workers are various and complicated, formulating the main difficulty and
      challenge of imported malaria control.

PMID- 29469256
TI  - [Epidemiological analysis of malaria prevalence in Nanjing City from 2010 to
      2015].
AB  - OBJECTIVE: To analyze the epidemiological characteristics of malaria in Nanjing
      City, so as to provide the evidence for further formulating and adjusting the
      malaria prevention and control strategy. METHODS: The data of malaria situation,
      malaria cases and epidemiological investigations were collected from the Internet
      Reporting System in Nanjing City from 2010 to 2015 and analyzed statistically.
      RESULTS: A total of 137 confirmed malaria cases were reported in Nanjing City
      from 2010 to 2015, including 102 falciparum malaria cases (74.45%), 33 vivax
      malaria cases (24.09%), one ovale malaria case (0.73%) and one quartan malaria
      case (0.73%). Among the 137 malaria cases, 126 cases (91.97%) were imported from
      foreign countries, 2 cases (1.46%) were infected locally, and nine cases (6.57%)
      were imported from other provinces in China. Among the 126 overseas imported
      cases, 117 cases were imported from African countries and 9 from Asian countries.
      These malaria cases were majorly young men working as migrant workers, laborers
      and technical persons. About 19.30% of the cases went to hospital on onset day,
      and 55.65% were confirmed by medical institutions as malaria in the same day. The
      majority of diagnosis institutions were municipal hospitals (74.45%).
      CONCLUSIONS: The number of malaria cases in Nanjing City is declining year by
      year. The local infections are eliminating gradually. However, the situation of
      imported malaria from overseas is still serious. Therefore, the surveillance work
      and health education still should be strengthened, so as to reduce the risk of
      imported malaria.

PMID- 29469257
TI  - [Analysis of human intestinal helminth infections in Yancheng City, Jiangsu
      Province from 2006 to 2015].
AB  - OBJECTIVE: To investigate the epidemiological trend of human intestinal helminth
      infections in Yancheng City, Jiangsu Province from 2006 to 2015, so as to provide
      the evidence for formulating further control strategies. METHODS: The
      surveillance data of human intestinal helminth infections were collected and
      analyzed in Yancheng City from 2006 to 2015. RESULTS: From 2006 to 2015, 110 746
      person-times of residents in Yancheng City were surveyed in Yancheng City, and 1
      732 samples were positive of human intestinal helminth infections. The infection
      rate of human intestinal helminthes was highest in 2006 [4.59% (410/8 941)], and
      lowest in 2013 [0.19% (23/12 165)]. The infection rate of human intestinal
      helminthes was significantly decreased over time (chi2 = 27.78, P < 0.001). The
      human infection rates of Ascaris lumbricoides, hook worm and Trichuris trichura
      were all decreased over time (Z = -27.75, -22.23 and -16.17, all P < 0.001) from
      2006 to 2015, with the reduction rates of 96.57%, 92.31% and 96.47%,
      respectively. The average EPG of A. lumbricoides, hook worm and T. trichura were
      2 534, 360 and 154 respectively, and 1 694 (97.81%) cases were light infections.
      Totally 1 174 cases of Enterobius vermicularis were found in children under 12
      years old, and the cases were decreased over time (chi2 = 12.46, P < 0.001).
      CONCLUSIONS: The infection rate of human intestinal helminthes in Yancheng City
      decreases over time from 2006 to 2015, and the control work is effective. The
      control work of focus groups and environmental management and health education
      should be strengthened in the future.

PMID- 29469258
TI  - [Investigation on Toxoplasma gondii infection and awareness of toxoplasmosis
      related knowledge in women with poor pregnant outcomes in Wuxi City].
AB  - OBJECTIVE: To investigate the prevalence of Toxoplasma gondii infection and
      awareness of toxoplasmosis-related knowledge among women with poor pregnant
      outcomes in Wuxi City. METHODS: A total of 217 women with poor pregnant outcomes
      from Wuxi City during the period of January 2011 to December 2015 were randomly
      selected as the study subjects (a study group), while 250 women with normal
      pregnancy were served as controls (a control group). The sero-prevalence of T.
      gondii infection was detected by using ELISA and compared between the study and
      control groups. The awareness of toxoplasmosis-related knowledge was investigated
      by using a self-designed questionnaire and compared between the study and control
      groups. RESULTS: The positive rate of anti-Toxoplasma antibody was 30.88% in the
      study group, which was significantly higher than that (8.8%) in the control group
      (chi2 = 36.7, P < 0.01). The positive rates of anti-Toxoplasma IgG and IgM
      antibodies were 20.74% and 10.14% in the study group respectively, which were
      significantly higher than those (6% and 2.8%) in the control group (chi2 = 22.53
      and 10.74, both P values < 0.01). In addition, the positive rates of anti
      Toxoplasma, anti-Toxoplasma IgG and IgM antibodies were significantly higher in
      the women with missed miscarriage, natural abortion, stillbirth and birth defect
      than those in the women with normal pregnancy (all P values < 0.05). The
      awareness rates of "Do you hear about Toxoplasma or toxoplasmosis?" (P < 0.01),
      "Do you know that breeding pet cats or dogs may cause Toxoplasma infection?" (P <
      0.05) and "Do you know that pregnancy women require the detection of Toxoplasma
      infection?" (P < 0.01) were significantly lower in the study group than those in
      the control group, while no significant differences were seen in the awareness
      rates of "Do you know that eating hot pot may cause Toxoplasma infection?", "Do
      you know that the use of chopping block in regardless of cooked and uncooked food
      may cause Toxoplasma infection?", "Do you know that Toxoplasma infection may
      transfer from mother to fetus?", "Do you know that Toxoplasma infection may cause
      adverse pregnant outcomes like abortion, stillbirth or fetal abnormalities ?",
      and "Do you know that the women infected with T. gondii during pregnancy require
      treatment?" between the two groups (all P values > 0.05). CONCLUSIONS: This study
      demonstrates higher prevalence of T. gondii infection in women with poor pregnant
      outcomes than in those with normal pregnancy in Wuxi City. Considering the harm
      of T. gondii infection during pregnancy and the low awareness of toxoplasmosis
      related knowledge in pregnant women, the health education of toxoplasmosis
      related knowledge should be strengthened, especially for pregnant women, so as to
      reduce the prevalence of T. gondii infection among pregnant women to improve the
      better child-bearing and rearing level.

PMID- 29469259
TI  - [Analyais of Toxoplasma gondii infection and related factors among special
      population in Changzhou City, Jiangsu Province].
AB  - OBJECTIVE: To understand the prevalence of Toxoplasma gondii infection and
      related factors among special population in Changzhou City, so as to provide the
      evidence for formulating toxoplasmosis prevention measures. METHODS: The venous
      blood was collected from participants in Changzhou City for detecting IgG and IgM
      antibodies against T. gondii by ELISA; and an epidemiological questionnaire
      investigation was also conducted. RESULTS: Among the total 400 respondents
      detected, the prevalence of T. gondii infection was 15.0% and the positive rates
      of IgG and IgM were 15.0% and 0.8%, respectively. The T. gondii infection rates
      of pregnant women, HIV/AIDS patients, patients with neoplasia, and livestock and
      poultry breeding and processing workers were 11.0%, 11.0%, 24.0% and 14.0%,
      respectively. As the age increased, the infection rate of T. gondii showed an
      upward trend, with the highest infection rate (21.6%) among the group of
      respondents aged above 50 years. The infection rates of groups with different
      education levels were statistically different (chi2 = 11.443, P < 0.05), and
      there was a trend that the infection rate decreased with the increase of
      education level. The prevalence of T. gondii infection in pregnant women was not
      significantly associated with the number of pregnancies and gestational age. The
      infection rate of T. gondii in the live-stock and poultry breeding and processing
      workers increased with the length of their working years. CONCLUSIONS: The
      prevalence of T. gondii infection among the special population in Changzhou City
      is high. Therefore, it is necessary to enhance the health education on the
      knowledge and information of prevention and control of toxoplasmosis, and to
      improve the awareness of personal protection, the hygiene practices and diet
      habits. In addition, more attention should be paid to T. gondii monitoring in the
      special population.

PMID- 29469260
TI  - [Splenic lymphocyte immune response induced by intranasal immunization with
      recombinant Toxoplasma gondii profilin in mice].
AB  - OBJECTIVE: To observe the splenocytes immune response elicited by different
      concentrations of recombinant Toxoplasma gondii profiling (rTgPRF) through the
      nasal route, and determine the optimal dose. METHODS: Fifty female BALB/c mice
      were randomly divided into 5 groups. The immunized groups were intranasally
      administered with 10, 20, 30 MUg or 40 MUg of rTgPRF that was separately
      dissolved in 20 MUl of phosphate-buffered saline (PBS) on days 0, 14, and 21
      respectively, while the control mice were given PBS solution instead. Two weeks
      after the last immunization, all mice were killed. Under asceptic conditions, the
      spleens from the immunized mice were dissected, and then the splenocyte
      proliferative responses in vitro were tested by CCK-8 kit. The levels of IFN
      gamma, IL-2, IL-4 and IL-10 of splenocyte culture supernatant were detected by
      ELISA. RESULTS: Compared to the control group, the splenocytes from the 30 MUg
      and 40 MUg groups exhibited a significantly higher proliferative response to
      rTgPRF (P < 0.05), and SI from the 30 MUg rTgPRF group was higher than that from
      the 40 MUg group (P < 0.05). The levels of IFN-gamma in all the immunized groups
      (P < 0.05) and IL-2 in the 20, 30 MUg and 40 MUg groups were significantly
      stronger than those in the control (P < 0.05), and the 30 MUg group presented the
      highest concentrations of IFN-gamma (P < 0.01) and IL-2 (P < 0.01). There were no
      statistical differences among the groups in the levels of IL-4 and IL-10.
      CONCLUSIONS: The intranasal immunization with rTgPRF can induce the
      splenocyteproliferation and Th1-type mediated immunity. The best immunized dose
      is confirmed as 30 MUg.

PMID- 29469261
TI  - [Establishment of a risk assessment model for laboratory biosafety of
      Cryptosporidium].
AB  - OBJECTIVE: To evaluate the risk assessment model of Cryptosporidium laboratory,
      so as to provide the basis for laboratory personnel engaging in the operation of
      Cryptosporidium. METHODS: Firstly, the risk factors of Cryptosporidium infection
      in laboratory were determined by the literature and Delphi, and then the weights
      of risk factors were determined by fuzzy analytic hierarchy process. A risk
      assessment model for laboratory biosafety of Cryptosporidium was established.
      RESULTS: Compared to the indexes, based on the risk assessment model, stool
      sample processing was the two steps in the laboratory with high risk of infection
      and high risk factors, with the combination weights of risk possibility and
      hazard rating were 0.111 and 0.107, respectively. CONCLUSIONS: The risk
      assessment model established is feasible. It can be used to make some suggestions
      for the related laboratory staff.

PMID- 29469262
TI  - [Comparison of Schistosoma japonicum development between single sexual infection
      and double sexual infection in mice and rabbits].
AB  - OBJECTIVE: To observe the development of Schistosoma japonicum after single
      sexual infection and double sexual infection respectively. METHODS: A single
      Oncomelania hupensis snail was infected by a single schistosome miracidium. The
      larva were induced and released from the snail after 60-day incubation at 26 C.
      The mice were infected by the larva (single sexual infection) and dissected 40
      days after the infection. All the worms were collected and the sex of the larvae
      was determined by the sex of the adult worms. Then, the mice and rabbits were
      infected by single sex of larvae (single sexual infection) and double sex of
      larvae (double sexual infection) respectively. The mice and the rabbits were
      dissected 40 days after the infection. All the worms were collected and measured
      under a microscope. RESULTS: All the male or female worms were collected from the
      mice and rabbits after single sexual infection. There were three main forms of
      worms after dissection of double sexual infection of mice and rabbits: folded
      mature male and female, male or female. Few folded male and immature female were
      found. Only the double sexual larva infected mice or rabbits had schistosome eggs
      in the liver and the liver had typical schistosome egg nodules. The single sexual
      larva infected mice or rabbits had no schistosome eggs or schistosome egg nodules
      in the liver tissues. The single male larva could develop to worms with the
      testis, and with a little smaller size compared to the mature folded male, while
      the single sexual infection female worm could not develop to the mature stage
      with much thinner and smaller compared to the mature folded female. CONCLUSIONS:
      The male or female worms from single sexual infection are smaller than those from
      double sexual infection (mature worms - folded male and female). So it is
      necessary to check single sex worms in vessels of intestinal mucosa thoroughly in
      the sentinel mice when no schistosome eggs were found in the liver.

PMID- 29469263
TI  - [Investigation on overwintering mosquitoes in Taibaihu District, Jining City].
AB  - OBJECTIVE: To investigate the species, density and distribution of the
      overwintering adult mosquitoes in Taibaihu District, Jining City. METHODS: The
      overwintering adult mosquitoes were monitored by visual observation in Taibaihu
      District, Jining City from December 2015 to March 2016. The mosquitoes were
      collected and dissected to observe the body fat accumulation and ovarian
      development situation. RESULTS: Totally 1 677 mosquitoes were captured and all of
      them were Culex pipiens pallens. The highest positive rate of overwintering
      mosquitoes was in sweet potato cellars and greenhouses, with the positive rates
      of mosquitoes of 98.25% (56/57) and 81.36% (48/59) respectively. The accumulation
      of the fat body in the female mosquitoes plummeted from late February, and
      disappeared in middle March. CONCLUSIONS: The adults of Culex pipiens pallens can
      over-winter in Taibaihu District, Jining City, and locate in sweet potato cellars
      and greenhouses mainly. The control work of adult mosquitoes should be
      strengthened in the overwintering period.

PMID- 29469264
TI  - [Schistosomiasis surveillance after interruption of schistosomiasis transmission
      in Xiuzhou District, Jiaxing City].
AB  - OBJECTIVE: To analyze the endemic situation of schistosomiasis after its
      interruption of transmission in Xiuzhou District, Jiaxing City, Zhejiang
      Province, so as to provide the references for future surveillance work. METHODS:
      The data of schistosomiasis and Oncomelania hupensis snails in Xiuzhou District
      were collected and analyzed statistically. RESULTS: From 1994 to 2015, totally
      975 village-times were investigated for O. hupensis snails, and the accumulated
      area of 4 385.31 hm2 was surveyed. Twenty former snail sites were reoccurring,
      with an area of 32.61 hm2. An area of 57.71 hm2 was supplied with snail
      eradication measures. Totally 11 941 snails were dissected and no schistosome
      infected snails were found. The serum and stool tests were performed to 221 794
      and 3 731 residents respectively, and no local infection cases but four imported
      cases were found. CONCLUSIONS: The endemic situation of schistosomiasis in
      Xiuzhou District is stable after the transmission was interrupted. However, there
      are imported schistosomiasis cases, and therefore, the prevention of imported
      infection source is the focus of surveillance work.

PMID- 29469265
TI  - [Analysis of imported malaria epidemic situation and implication for prevention
      and control strategy in Guangxi Zhuang Autonomous Region in 2014].
AB  - OBJECTIVE: To analyze the epidemic characteristics of the imported malaria cases
      in Guangxi Zhuang Autonomous Region in 2014, so as to assess the transmission
      risk and explore the prevention and control strategy. METHODS: The data of the
      malaria epidemic situation in the network direct report system of Guangxi in 2014
      and the annual report of malaria epidemic situation in 14 cities were collected.
      The epidemiological information of the imported malaria cases was analyzed.
      RESULTS: A total of 184 malaria patients were reported in Guangxi in 2014, with a
      descent rate of 85.29% when compared to that in 2013 (1 251 cases), and the
      incidence rate was 0.35/100 000. All the cases were imported from abroad, and
      four species of Plasmodium were found in their blood samples. The number of
      falciparum malaria cases was the most (49.46%), followed by the ovale malaria
      cases (32.07%). All the cases were distributed in 32 counties (districts) of 11
      cities, and 65.76% of them were distributed in Shanglin County. Most of the cases
      were male (98.37%), and those aged in 20-49 years accounted for 87.50%. The
      imported cases came from 14 countries of Africa (86.41%) and 2 countries of
      Southeast Asia (13.59%), in which, 48.37% of the cases were imported from Garner.
      The main occupation of the cases in abroad was gold mining work (86.96%). The
      cases were reported all the year around, with no obvious seasonality. The
      interval time of back home to attack of the patients with tertian malaria and
      ovale malaria was longer. CONCLUSIONS: Africa and Southeast Asia is the main
      source of imported malaria cases in Guangxi, and the migrant workers returning
      home may have the risk of malaria recurrence, which should be paid enough
      attention to.

PMID- 29469266
TI  - [Investigation on awareness rates of malaria prevention knowledge among residents
      and students in Huai'an District, Huai'an City].
AB  - OBJECTIVE: To understand the awareness status on malaria control knowledge of
      residents, primary and middle school students in Huai'an District, Huai'an City,
      so as to provide the evidences for promoting the malaria elimination process in
      this district. METHODS: Three towns in Huai'an District were selected randomly,
      and one village, one primary school and one junior middle school in each town
      were chosen as the investigation sites. The residents over 18 years old, the
      primary school students in Grade 4 to 6, and the junior middle students in the
      investigation sites were investigated by questionnaires to understand their
      awareness status on knowledge of malaria control. RESULTS: Totally 305 residents
      and 618 students were investigated. The awareness rate of students was 89.97%,
      and the rates of the junior middle school students and primary school students
      were 85.94% and 94.10%, respectively, the difference between them was
      statistically significant (P<0.01). The awareness rate of the residents was
      80.98%, which was lower than that of the students (P<0.05). For the students, the
      awareness rate on "precaution of malaria" (96.74%) was the highest, while that on
      "drug of malaria" (68.93%) was the lowest. For the residents, the rate on
      "transmission route of malaria" (95.08%) was the highest, that on "4.26 is
      Malaria Day" (64.26%) was the lowest. Expect the items of "transmission route of
      malaria" and "precaution of malaria" (both P>0.05), the differences of the
      awareness rates on all the other items between the students and residents were
      statistically significant (all P<0.01). CONCLUSIONS: Although the awareness rates
      of malaria control knowledge in the population of Huai'an District, Huai'an City
      have achieved the goal of the relevant requirement, the health education on
      malaria control still should be strengthened, especially for the primary
      students, female residents and exported labor service personnel.

PMID- 29469267
TI  - [Investigation on current situation of malaria blood examinations in township
      level hospitals of Nantong City].
AB  - OBJECTIVE: To understand the quality of malaria blood examinations in township
      level hospitals, so as to provide the evidence for continuing the malaria blood
      examinations in the stage of post-malaria elimination. METHODS: A total of 64
      township hospitals were investigated and 640 negative malaria blood slides were
      scored individually according to 10 indicators in "Malaria Elimination Technical
      Scheme" in 2013 and 2014. The single and multiple indicators were calculated, and
      the work of blood examinations and situation of technicians were investigated.
      The data of malaria blood examinations and patient discovery in township
      hospitals of Nantong City were collected and analyzed during the period of 2011
      2014. RESULTS: For the single indicator, 29.5% of the thick blood films did not
      reach the standard, and 35.8% of thin blood films did not reach the standard. For
      the multiple indicators, blood slides with more than 4 indicators below the
      standard (poor quality) accounted for 32.5%. From malaria blood examinations and
      malaria situation, the number of slides was 194 635 during the period of 2011
      2014, and there were no local vivax malaria casesin 4 consecutive years from 2011
      to 2014, and local malaria has been effectively controlled in Nantong City. For
      health facilities where malaria patients initially presented, the township and
      village level accounted for 16.3%, and county and higher level accounted for
      83.7%. CONCLUSIONS: The quality of malaria blood examinations in township level
      hospitals of Nantong City is not high and the microscopic examination has a
      relatively low efficiency in the discovery of malaria cases. A new model for
      malaria blood examinations needs to be further explored.

PMID- 29469268
TI  - [Epidemiological analysis of malaria prevalence in Taixing City from 2005 to
      2015].
AB  - OBJECTIVE: To understand the malaria prevalence and epidemic characteristics in
      Taixing City from 2005 to 2015, so as to provide the evidences for formulating
      the prevention and control strategy. METHODS: The malaria data of Internet
      reported cases as well as the reports on epidemiological survey of malaria cases
      in Taixing City from 2005 to 2015 were collected and analyzed with the methods of
      descriptive statistics and correlation analysis. RESULTS: A total of 61 malaria
      cases were reported in Taixing City from 2005 to 2015, including 4 local cases
      and 57 imported cases. There were 9 cases of vivax malaria, 47 cases of
      falciparum malaria, 2 cases of malariae malaria, and 3 cases of ovale malaria.
      There was no seasonality in the occurrence of imported malaria. Though there was
      no correlation between the times of malaria attack and the duration for going out
      (r = 0.154, P = 0.253), there was a negative correlation between the former and
      the timeliness for visiting a doctor (r = -0.312, P = 0.014). CONCLUSIONS: The
      malaria cases are mainly imported ones in Taixing City, and the Plasmodium
      species of infection are diverse. Imported malaria overseas remains the key point
      for malaria control in Taixing City.

PMID- 29469269
TI  - [Investigation on Toxoplasma gondii infection in reproductive women in Shandong
      Province].
AB  - OBJECTIVE: To investigate the Toxoplasma gondii infection situation and relative
      factors in reproductive women in Shandong area, so as to provide the evidences
      for establishing strategies for reducing the birth defects and improving the
      quality of population. METHODS: A total of 5 386 reproductive women who visited
      hospitals at county and city levels in Shandong region from January 2013 to
      December 2015 were treated as the research objects, and their venous blood
      samples were collected to detect the antibodies (IgG and IgM) against T. Gondii
      in serum. Meanwhile, the related risk factors of T. gondii infection were
      surveyed by questionnaires. RESULTS: Among the 5 386 reproductive women, 623 ones
      were positive for IgG antibody and the positive rate was 11.56%, and 328 ones
      were positive for IgM antibody and the positive rate was 6.21%. The single factor
      analysis showed that the pregnant status (chi2 = 13.12, P < 0.01), whether the
      residences were in downtowns or counties (chi2 = 6.27, P < 0.05), whether having
      animal contact history (chi2 = 10.46, P < 0.01), and whether eating half-baked
      foods (chi2 = 21.19, P < 0.01) were related to T. gondii infection. CONCLUSIONS:
      The T. gondii infection rate of reproductive women in Shandong Province is high;
      the related risk factors include pregnant status, residence, degree of intimate
      contact with animal, and whether eating half-baked foods. It suggests that the
      detection of T. gondii infection and health education in reproductive women
      should be strengthened.

PMID- 29469270
TI  - [Investigation on current status of Toxoplasma gondii infection among pregnant
      women and exploration of risk factors in some areas of Lhasa City, Tibet].
AB  - OBJECTIVE: To understand the current status of Toxoplasma gondii (TOX) infection
      among pregnant women and to explore the risk factors in some areas of Lhasa City,
      Tibet. METHODS: From 2015 to 2016, 3 districts (counties) of Lhasa City were
      chosen as the investigation sites, and 200 pregnant women in each district
      (county) were selected as the investigation objectives. Meanwhile, 450 pregnant
      women from Xuzhou, Yangzhou, Wuxi cities in Jiangsu Province were chosen as the
      control. Then the blood samples of the pregnant women both in Lhasa and Jiangsu
      were detected by ELISA for TOX antibodies IgG, IgM, and the detection results
      were analyzed and compared. In addition, the individual information of the
      pregnant women in Lhasa City was surveyed by questionnaires, and the related risk
      factors of TOX infection were analyzed. RESULTS: Among 600 pregnant women
      investigated in Lhasa City, there were 99 pregnant women with positive TOX
      antibodies, and the positive rate was 16.50%, which was significantly higher than
      that (5.11%) of the pregnant women in Jiangsu Province (P < 0.05). There was no
      statistically significant difference among the 3 districts (counties) of Lhasa
      City in the positive rates of pregnant women (P > 0.05). The positive rates of
      the women who preferred raw meat or had the intimate contact with animal were
      high. CONCLUSIONS: Compared with Jiangsu Province, the infection rate of TOX
      among pregnant women in Lhasa City is high. Therefore, the comprehensive measures
      including health education, early examination and treatment should be taken
      actively, so as to prevent and control TOX infection in this area.

PMID- 29469271
TI  - [Investigation on species of Limacodidae on Prunus cerasifera and sycamore in
      urban area of Wuhu City].
AB  - OBJECTIVE: To investigate the species of Limacodidae and the biological habits on
      Prunus cerasifera and sycamore in the urban area of Wuhu City, so as to provide
      the reference for the prevention and control of the diseases caused by
      Limacodidae. METHODS: Two observation places were selected in the urban area of
      Wuhu City, and the survey period of the first observation place (A) was from 2014
      5-4 to 2014-11-2, and eucleid caterpillar was observed and collected every Sunday
      (a total of 27 times); the survey period of the second observation place (B) was
      from 2014-1-5 to 2014-12-28, and eucleid caterpillar was observed and collected
      every Sunday (a total of 52 times). The eucleid caterpillars were collected by
      the visual inspection and artificial direct collecting method, and then they were
      identified and classified by the naked eye direct observation and the direct
      observation with the help of the anatomical lens in the laboratory. RESULTS:
      There were seven kinds of identified Limacodidae from the two observation places
      and their occurrence regularity, the species composition ratio, and natural
      enemies were understood. CONCLUSIONS: Limacodidae larvae not only are the
      defoliator of the ornamental forests, but also harm the health of residents, that
      is they can cause eucleid larva dermatitis. Therefore, we should strengthen the
      prevention and control of Limacodidae, reducing its impact on the lives of the
      residents.

PMID- 29469272
TI  - [Schistosomiasis control progress and endemic situation in Sichuan Province].
AB  - OBJECTIVE: To understand the schistosomiasis control progress and endemic
      situation, so as to provide the evidence for formulating the strategy of
      schistosomiasis elimination in Sichuan Province. METHODS: The schistosomiasis
      history data, working reports of schistosomiasis prevention and control,
      schistosomiasis surveillance data, and data of schistosomiasis prevention and
      control capacity were collected and analyzed for the schistosomiasis control
      progress and epidemic situation in Sichuan Province from 2004 to 2015. RESULTS:
      There were 63 schistosomiasis endemic districts in 11 cities in Sichuan Province,
      and the standard of schistosomiasis transmission interruption was achieved in the
      whole province in 2015. Currently, the area with Oncomelania hupensis snails was
      2 537.54 hm2, and there were 1 769 advanced schistosomiasis patients. From 2004
      to 2015, the accumulated survey area with snails was 433 065.80 hm2, and the area
      of snail control by molluscicides was 251 259 hm2. There were 26.017 144 million
      person-times of schistosomiasis blood tests and 7.89 million person-times of
      chemotherapy. There were 1.276 117 million head-times of cattle that received the
      schistosomiasis examinations. The schistosomiasis patients and livestock and the
      area with snails were decreased year by year. Since 2010, there were no local
      schistosome-infected residents and livestock and since 2004, there were no
      schistosome-infected snails. However, in some area, the professional personnel
      were less, the technology and hardware lagged behind, and the schistosomiasis
      prevention and control capacity was weak. CONCLUSIONS: Sichuan Province achieved
      the standard of schistosomiasis transmission interruption in 2015. In the future,
      the comprehensive schistosomiasis prevention and control strategy still should be
      strengthened, including the promotion of schistosomiasis prevention and control
      capacity, establishment of sensitive early-warning surveillance system, and
      implementation of accurate schistosomiasis prevention and control, in order to
      consolidate the control achievements and realize the aim of schistosomiasis
      elimination as soon as possible.

PMID- 29469273
TI  - [Analysis of results of technique competition for parasitic disease diagnosis in
      Class A tertiary hospitals in Jiangxi Province, 2015].
AB  - OBJECTIVE: To understand the capability of parasitic disease diagnosis among
      professionals from the clinic laboratory of Class A tertiary hospitals in Jiangxi
      Province. METHODS: The teams that took part in the competition were formed from
      20 Class A tertiary hospitals, with 2 contestants per team. The competition
      contents included written examination and skill operation. The written
      examination involved the life cycle of parasites, immunological basis, detecting
      techniques, etiological diagnosis etc., and the skill operation involved making
      and dying thin and thick blood smears, making Kato-Katz's fecal thick smears, as
      well as microscopic examinations of smears. RESULTS: A total of 40 participants
      took part in the competition. Their total average score was 97.3+/-22.4 with the
      pass rate of 15.0%, in which the mean score of theoretical knowledge was 56.6+/
      12.8 with the pass rate of 52.5%, and the mean score of skill operation was
      40.8+/-12.4 with the pass rate of 5.0%. In the written examination, the scoring
      rate of the life cycle of soil-transmitted helminths was the highest (90.0%), and
      the rate of the basic knowledge of food-borne parasites was the lowest (31.5%).
      Both the pass rates of blood smear making and examination were higher than those
      of Kato-Katz's thick smears, and the differences were statistically significant
      (both P < 0.05). The detection rates of Plasmodium vivax, Plasmodium falciparum,
      Plasmodium ovale and negative slides of the contestants were 38.8%, 45.0%, 35.0%
      and 25.0% respectively. As to the microscopic examination of helminth eggs, the
      detection rate of Trichuris trichiura egg was the highest (87.5%), and the rate
      of the Sparganum mansoni egg was the lowest (2.5%). The scores of Kato-Katz's
      thick smear making and examination of the contestants from the provincial level
      hospitals were higher than those from the city level hospitals (both P < 0.05),
      and the score of those from teaching hospitals in Kato-Katz's thick smear making
      was higher than that of those from non-teaching hospitals (P < 0.05).
      CONCLUSIONS: The technique level of professionals from the clinic laboratory of
      the Class A tertiary hospitals cannot meet the needs of the diagnosis of
      parasitic diseases in Jiangxi Province, which should arouse the attention of the
      health authorities and hospitals.

PMID- 29469274
TI  - [Study on discourse right construction of China's medical aid to Africa].
AB  - OBJECTIVE: To analyze the discourse right construction of China's medical aid to
      Africa, so as to provide evidences for improving the effect and sustainable
      development of China's medical aid to Africa. METHODS: The documents of the
      discourse right that China constructed in the medical aid to Africa were selected
      at different periods as discourse samples. The achievement and deficiency were
      analyzed from four aspects, namely confident, charismatic, influential, and
      dominant. RESULTS: China's medical team made much in the discourse right
      construction in their aid to Africa, but some China's medical team members were
      still too cautious and too low-key. China's medical team gained the trust of the
      people of Africa, but the language communication difficulties still hampered in
      China's medical aid to Africa. Chinese medical team were widely praised by the
      African society, but in the west, some African media, even China's media still
      neglected to report China's doctors. China's international discourse right were
      greatly improved, but western countries still dominated the public opinion.
      CONCLUSIONS: China should refer to the actual situation of medical aid to Africa
      to strengthen the construction of discourse right.

PMID- 29469275
TI  - [Investigation on Oncomelania hupensis snail status in Hailing District, Taizhou
      City from 2007 to 2014].
AB  - OBJECTIVE: To understand the current status of Oncomelania hupensis snails and
      the change rules, so as to provide the evidence for formulating the snail control
      strategy. METHODS: The data of snails were collected and the factors influencing
      the changes of snail status were investigated, and all the data were analyzed in
      Hailing District from 2007 to 2014. RESULTS: There were 18 environments with
      snails in 17 villages of 3 townships in Hailing District from 2007 to 2014. The
      snail area was 7.832 4 hm2. Among these environments and snail areas, 6
      environments and 2.134 5 hm2, snail area were detected by the village snail
      investigation groups, and 12 environments and 5.697 9 hm2 snail area were
      detected by the township snail investigation groups. In addition, in 5 non
      endemic villages, 3.126 3 hm2 snail area was found. In 2008, 2012 and 2013, a
      total of 2.274 0 hm2 snail area was found again. CONCLUSIONS: In recent years,
      the snail situation rises again after schistosomiasis transmission has been
      interrupted. Therefore, this situation should be paid attention to.

PMID- 29469276
TI  - [Analysis of epidemic situation of malaria in Wuxi City from 2005 to 2014].
AB  - OBJECTIVE: To understand the epidemiological characteristics of malaria in Wuxi
      City, and explore effective strategies and measures for malaria elimination.
      METHODS: The data on malaria cases in Wuxi from 2005 to 2014 were collected and
      analyzed. RESULTS: In Wuxi City, from 2005 to 2014, 201 malaria cases were
      reported, of which, there were 52 local cases and 149 imported cases. Totally 156
      malaria cases were reported from 2005 to 2009, of which 6 cases were infected
      with Plasmodium falciparum, and 45 malaria cases were reported from 2010 to 2014,
      of which 23 cases were infected with P. falciparum. From 2005 to 2009, the ratio
      of male to female was 2.39:1. Migrant workers, farmers and workers were the major
      infected populations, with a proportion of 41.03%, 17.95% and 9.62%,
      respectively. From 2010 to 2014, the ratio of male to female was 10.25:1.
      Workers, farmers and migrant workers were the major infected populations, with a
      proportion of 37.78%, 11.11% and 6.67%, respectively. The peak of malaria
      incidence was observed from May to October. From 2005 to 2009, most cases were
      reported by CDCs, and from 2010 to 2014, most cases were reported by medical
      institution. There was an increase in proportion of P. falciparum. CONCLUSIONS:
      The control and prevention of malaria should focus on imported cases in the
      future in Wuxi. The doctors should improve the capacity of malaria diagnosis and
      treatment.

PMID- 29469277
TI  - [Analysis of epidemic situation of imported malaria in Donghai County from 2005
      to 2015].
AB  - OBJECTIVE: To understand the epidemic situation, epidemiological characteristics
      and clinical features of imported malaria in Donghai County, Lianyungang City
      from 2005 to 2015. METHODS: The epidemiological data of imported malaria in
      Donghai County from 2005 to 2015 were collected and analyzed by the descriptive
      epidemiological method. RESULTS: A total of 126 imported malaria cases were
      reported in Donghai County from 2005 to 2015, including 101 falciparum malaria
      cases (80.19%), 13 ovale malaria cases (10.32%), 7 vivax malaria cases (5.56%), 4
      quartan malaria cases (3.17%), and 1 case with mixed infection (0.79%). These
      cases were distributed in 14 towns, and mainly in 4 towns namely Niushan,
      Tuofeng, Shiliu, and Huangchuan, and the cases in the 4 towns accounted for
      63.49% of the total cases. The cases occurred in the whole year, but the peak
      period of the disease was in April, which was related to the returned time of
      these patients from foreign countries. All the patients were male and aged from
      20 to 55 years, and those aged from 20 to 50 years accounted for 90.70%.
      CONCLUSIONS: The epidemic situation of imported malaria presents a rising trend
      in Donghai County in recent 10 years. To control imported malaria, the above
      mentioned 4 towns with more migrant construction workers and businessmen should
      be treated as key areas. Meanwhile, the floating population management, disposal
      of the malaria epidemic spots, mosquito vector monitoring as well as health
      education should be strengthened.

PMID- 29469278
TI  - [Evaluation of health education of medium- and long-term planning of
      schistosomiasis prevention and control in Kunshan City].
AB  - OBJECTIVE: To evaluate the effect of health education on schistosomiasis in
      Kunshan City, so as to provide the evidence for making the consolidating strategy
      in the late stage of interruption of schistosomiasis transmission. METHODS: The
      residents, middle school students and elementary school students were randomly
      sampled from one community, one middle school and one elementary school of each
      of two towns and they were investigated with interviews and questionnaires for
      the implementation of health education on schistosomiasis prevention and control.
      RESULTS: A total of 452 middle school students (232 cases) and primary school
      students (220 cases) were surveyed. The awareness rate of total schistosomiasis
      knowledge was 98.21% among the students (the awareness rate of basic
      schistosomiasis knowledge was 98.42% and the awareness rate of preventive
      schistosomiasis knowledge was 98.01%). Among the 220 elementary school students,
      the awareness rate of total schistosomiasis knowledge was 97.21% (the awareness
      rate of basic schistosomiasis knowledge was 97.60% and the awareness rate of
      preventive schistosomiasis knowledge was 96.82%). Among the 232 middle school
      students, the awareness rate of total schistosomiasis knowledge was 99.17% (chi2
      = 34.661, compared with the rate of the elementary school students) [the
      awareness rate of basic schistosomiasis knowledge was 99.20% (chi2 = 13.045,
      compared with the rate of the elementary school students) and the awareness rate
      of preventive schistosomiasis knowledge was 99.14% (chi2 = 21.796, compared with
      the rate of the elementary school students)]. There were significant differences
      between the elementary school students and middle school students in above
      mentioned awareness rates (all P < 0.001). There were schistosomiasis health
      education materials or teaching plans in all the four schools. Among the 402
      residents surveyed, the awareness rate of total schistosomiasis knowledge was
      98.87%. CONCLUSIONS: The effect of health education on schistosomiasis prevention
      and control is very well, and the total awareness rate of schistosomiasis
      prevention and control knowledge among the population has reached the goal (more
      than 95%) of the medium- and long-term planning of schistosomiasis prevention and
      control in Kunshan City.

PMID- 29469279
TI  - [Surveillance on schistosomiasis after its transmission interruption in Baoying
      County, Jiangsu Province].
AB  - OBJECTIVE: To understand the endemic situation of schistosomiasis after its
      transmission interruption in Baoying County, so as to provide the evidence for
      adjusting the prevention and control strategy. METHODS: The data of
      schistosomiasis surveillance in Baoying County from 1988 to 2015 were collected
      and retrospectively analyzed. RESULTS: The schistosomiasis surveillance has been
      established since it was interrupted in Baoying County in 1987. The total
      surveyed area with Oncomelania hupensis snails was 21 269.95 hm2, but no living
      snails were found. The number of schistosomiasis examinations of residents was
      163 196 person-times, and 270 person-times were positive in serum test, 26 person
      times were positive in stool test. No positive cases were found since 1997. The
      number of schistosomiasis tests of livestock was 2 180 cattle-times but no
      infection was found. CONCLUSIONS: No schistosome infected snails or livestock are
      founded in Baoying County for last 28 years, and no patients are founded for last
      11 years. The effect of schistosomiasis control is steady.

PMID- 29469280
TI  - [Application effect of pericardial devascularization plus gastric fundus
      transaction in advanced schistosomiasis].
AB  - OBJECTIVE: To discuss the effect of pericardial devascularization plus gastric
      fundus transaction in advance schistosomiasis patients with portal hypertension.
      METHODS: Thirty-six advanced schistosomiasis patients with portal hypertension
      treated with devascularization plus gastric fundus transaction (a portal
      hypertension group), as well as 10 patients treated with modified Sugiura
      operation (a modified Sugiura operation group) in the Third People's Hospital of
      Yangxin County since 2006 were chosen as the observation objects, and the
      clinical effects of the two groups were observed and compared. RESULTS: The
      operation time, indwelling time of stomach tube, time to taking food after
      operation, drainage tube removal time of the portal hypertension group were all
      shorten than those of the modified Sugiura operation group (all P<0.05). The
      hospitalization expenses of the two groups were (25 466.00 +/- 2 888.48) Yuan and
      (34 517.10 +/- 4 948.39) Yuan respectively, and the difference was also
      statistically significant (P<0.05). The incidence rates of portal thrombosis of
      the portal hypertension group and modified Sugiura operation group were 33.33%
      (12/36) and 40.00% (4/10), respectively, and the incidence rates of
      rehaemorrhagia of the two groups 12 months after the operation were 16.67% (6/36)
      and 10.00% (1/10), respectively, but the differences had no statistically
      significance (both P > 0.05). In addition, 1 case with delayed gastric emptying
      and 1 case with stomal leak of esophagus happened in the modified Sugiura
      operation group, while no corresponding complications happened in the portal
      hypertension group. CONCLUSIONS: Pericardial devascularization plus gastric
      fundus is a relatively easy procedure which has a good short-term clinical
      effect, and therefore it is suitable for application in primary hospitals.
      However, its long-term effect still needs further observation.

PMID- 29469281
TI  - [Advances in research of stem cell therapy for human parasitic diseases: a
      review].
AB  - The stem cell is a class of primitive cells with self-renewal, and multiple
      pluripotent potential capacities, which can differentiate into multiple
      specialized cells and generate human organs and tissues. Stem cell therapy is an
      interventional treatment that introduces new stem cells to damaged tissues, which
      facilitates the regeneration of trauma, disease and ageing-induced damaged human
      tissues to repair or replace the damaged tissues, thereby achieving the goal of
      disease treatment. It has been proved that the stem cell therapy is effective in
      the treatment of multiple human diseases, including cancer, diabetes,
      neurological disorders, autoimmune diseases, cardiovascular disorders and blood
      diseases. This review summarizes the advances in the research of stem cell
      therapy for human parasitic infections.

PMID- 29469282
TI  - [Research status of Schistosoma transcription factors].
AB  - Schistosomiasis is a kind of zoonosis with serious hazard, which is popular in
      many countries and regions in the world. One of the efforts for schistosomiasis
      prevent and control is developing new drugs and vaccines, and knowing the
      transcription regulation mechanism and the function of transcription factors will
      help us find the targets of new drugs and vaccines as soon as possible. This
      article reviews the progress of Schistosoma transcription factors and research
      methods.

PMID- 29469283
TI  - [Status and future development of surveillance of schistosomiasis in Jiangxi
      Province].
AB  - Jiangxi Province is one of serious endemic provinces with schistosomiasis
      japonica in China. The transmission control of schistosomiais has been achieved
      in whole province in 2015 after more than 60 years' great efforts. Of them, the
      surveillance has played an important role in the control of schistosomiasis.
      Based on the comprehensive analysis of the status of schistosomiasis epidemic,
      surveillance and challenges, this article exports the priority and development
      trend of surveillance after the achievement of transmission control of
      schistosomiasis in Jiangxi Province.

PMID- 29469284
TI  - [Sample unit size effects of spatial pattern of Oncomelania hupensis population
      in marshland schistosomiasis epidemic areas].
AB  - OBJECTIVE: To explore the sample unit size effects of spatial pattern of
      Oncomelania hupensis population in the marshland schistosomiasis epidemic areas.
      METHODS: The push-broom method was performed to survey the snails in the study
      site in a basic unit size of 0.33 m*0.33 m in Poyang Lake region of Jiangxi
      Province. After combining different amount of survey cells, the aggregation
      indicators, regression models and aggregating factor index were employed to study
      the spatial distribution pattern. RESULTS: The snail population was in
      aggregation pattern and the smaller sampling unit could produce higher degrees of
      aggregation. The regression models showed that the snails distributed in the form
      of individual groups with attraction with each other and the aggregation was
      related with the snail density. The clustering factor index demonstrated that the
      aggregation was introduced by aggregating behavior habit of the snails and
      environmental factors, or only by snail habit itself, and the aggregating habit
      of snails could be expressed better by the smaller sampling unit. CONCLUSIONS:
      The spatial pattern of O. hupensis population in the marshland schistosomiasis
      epidemic areas is in aggregation pattern, and the sample unit size can affect the
      calculation results of the related biological indices.

PMID- 29469285
TI  - [Spatial and temporal characteristics of distribution of Oncomelania hupensis in
      Eryuan County from 2005 to 2012].
AB  - OBJECTIVE: To study the spatial and temporal characteristics of Oncomelania
      hupensis in Eryuan County, Yunnan Province from 2005 to 2012, so as to provide
      the scientific evidence for snail surveillance and control. METHODS: Based on the
      geographic database of O. hupensis snail distribution from 2005 to 2012, the
      spatial and local autocorrelation analysis and "hot spots" analysis were applied
      to analyze the spatial and temporal characteristics of the snails. RESULTS:
      Percent of frames with O. hupensis snails in Eryuan County decreased as a whole
      from 2005 to 2012. The spatial clustering of global autocorrelation (Moran's I)
      was increasing from 2007 to 2012 and all Moran's I values showed statistically
      significance. The local spatial autocorrelation analysis indicated that the
      number of villages of High-High type of correlation model increased from 2 in
      2005 to 7 in 2012, which mainly clustered in plateau canyon areas. The infected
      snails with High-High type mainly distributed in plateau basin region in 2007.
      Further "hot spot" analysis found that the living snails gathered in Xinzhuang,
      Liantie, Xipo and Taiping nearby areas. CONCLUSIONS: The snail distribution in
      Eryuan has global and local spatial autocorrelations. The number of villages of
      High-High type of correlation increased. These findings provide the basis for
      target control of O.hupensis in the future.

PMID- 29469286
TI  - [Establishment of surveillance and forecast platform of schistosomiasis in key
      water regions in Hubei Province].
AB  - OBJECTIVE: To establish an expression platform of surveillance and forecast for
      schistosomiasis in key water regions of Hubei Province. METHODS: The platform of
      surveillance and forecast for schistosomiasis was established based on Google
      Earth, GIS Office software, network albums and network video stations. The
      results of the field surveillance and laboratory testing, and figures and videos
      were inputted into the established platform, and an information management file
      was set up to express the information of forecasting. RESULTS: The operation and
      expression platform based on Google Earth in key water regions of Hubei Province
      was successfully established. It was able to provide the forecasting data timely,
      to achieve off-site and real-time query and sharing. CONCLUSIONS: The platform
      based on Google Earth has preferable prospective on field application in Hubei
      Province.

PMID- 29469287
TI  - [Investigation on prevalence and risk factors of HIV/AIDS and Schistosoma
      japonicum, Ascaris lumbricoides and Trichuris trichiura infections in a rural
      community of southwestern China].
AB  - OBJECTIVE: To investigate the prevalence and risk factors of helminthic
      infections including Schistosoma japonicum, Ascaris lumbricoides and Trichuris
      trichiura and human immunodeficiency virus (HIV), and find out the association
      among them in a rural community of southwestern China. METHODS: A community-based
      cross sectional study was conducted. One town was selected randomly; the
      infections of S.japonicum, A.lumbricoides and T.trichiura were detected with the
      modified Kato-Katz thick smear method and HIV infection with the diagnostic Test
      Kit among all residents. A questionnaire survey was conducted to investigate the
      related risk factors. RESULTS: Among the participants, the infection rates of
      HIV, S.japonicum, A.lumbricoides and T.trichiura were 2.33%, 2.05%, 13.47% and
      30.59% respectively; 7.08% (31/438) were infected with both A.lumbricoides and
      T.trichiura; 0.23% (1/438) were co-infected with HIV and A.lumbricoides, and the
      same with HIV and T.trichiura. The multivariate logistic regression analysis
      showed that sex (male, OR=3.26, 95% CI:0.97, 10.95) and drug abuse (OR=72.86, 95%
      CI:18.51, 286.76) were significantly associated with HIV infection. Home toilet
      was negatively related to A.lumbricoides infection (OR=0.52, 95% CI:0.27, 0.98)
      and T.trichiura infection (OR=0.48, 95% CI:0.28, 0.80). Compared with the people
      in Villages Four, the people living in Village One were at a higher risk for
      A.lumbricoides infection (OR=3.14, 95% CI:1.35, 7.27), and compared with the
      people living in Village Four, the people living in Village Two and Village Three
      were more likely to be infected with T.trichiura (OR=3.73, 95% CI:1.92, 7.26;
      OR=4.53, 95% CI:2.12, 9.68). The people aged between 11 and 20 years had a higher
      T.trichiura infection risk than the people aged more than 50 years (OR = 3.72,
      95% CI:1.59, 8.67). There was a significant association between A.lumbricoides
      and T.trichiura infections (OR = 3.11, 95% CI:1.63, 5.93). There was no
      association between S.japonicum infection and related factors above mentioned.
      CONCLUSIONS: The infection rates of HIV, S.japonicum, A.lumbricoides and
      especially T.trichiura were rather high in this area, and therefore, the
      prevention and treatment of these diseases should be strengthened. Further
      studies on the relationship between HIV and the infections of helminths,
      especially S.japonicum are needed.

PMID- 29469288
TI  - [Application of ARIMA model on prediction of malaria incidence].
AB  - OBJECTIVE: To predict the incidence of local malaria of Hubei Province applying
      the Autoregressive Integrated Moving Average model (ARIMA). METHODS: SPSS 13.0
      software was applied to construct the ARIMA model based on the monthly local
      malaria incidence in Hubei Province from 2004 to 2009. The local malaria
      incidence data of 2010 were used for model validation and evaluation. RESULTS:
      The model of ARIMA (1, 1, 1) (1, 1, 0)12 was tested as relatively the best
      optimal with the AIC of 76.085 and SBC of 84.395. All the actual incidence data
      were in the range of 95% CI of predicted value of the model. The prediction
      effect of the model was acceptable. CONCLUSIONS: The ARIMA model could
      effectively fit and predict the incidence of local malaria of Hubei Province.

PMID- 29469289
TI  - [Investigation of two blood parasitic protozoa infection in farmed Macaca
      fascicularis in Guangxi Zhuang Autonomous Region].
AB  - OBJECTIVE: To investigate the infection situation of blood parasitic protozoa in
      farmed Macaca fascicularis in an animal breeding ground in Nanning, Guangxi
      Zhuang Autonomous Region, so as to provide the evidence for the prevention and
      control of human blood parasitic protozoa. METHODS: A total of 993 blood samples
      from farmed M. fascicularis were collected and stored on FTA cards. Among them,
      550 thin blood smears were made. Each 10 samples were mixed in groups, and then
      the Babesia spp. and Plasmodium spp. in the blood of M. fascicularis were
      detected by Nest-PCR and PCR, respectively. The positive groups were tested
      individually. The thin blood smears stained with Giemsa were examined
      microscopically when PCR reported the samples were positive. RESULTS: When
      detected by Nest-PCR, the positive rate of Babesia. microti was 6.95% (69/993);
      only 1 positive sample with Plasmodium inui was detected by PCR. Among the 22
      positive thin blood smears detected by PCR, 16 were determined with B. microti by
      microscopic examinations, on which the ring forms could be observed in the
      erythrocytes, but no hemozoin. CONCLUSIONS: The positive rate of B. microti in M.
      fascicularis in Guangxi Zhuang Autonomous Region is high, and the animal may play
      a role as a reservoir host in the transmission of B. microti. In the screening of
      B. microti with low infection density, Nest-PCR has a higher sensitivity.

PMID- 29469291
TI  - [Investigation on mites and insects breeding status of bed mats in college
      dormitories in Wuhu City].
AB  - OBJECTIVE: To understand the breeding situations of mites and insects from bed
      mats in dormitories in a college in Wuhu City, so as to provide evidences for
      improving the prevention and control of mites. METHODS: From March to May, 2015,
      the dust samples from bed mats in student dormitories were collected and detected
      for mites and insects by microscopy. In addition, the intervention measures
      including soaking the mats in the warm water, exposing the mats to the sunlight
      for a long time and cleaning up the indoor environment were carried out, and the
      breeding situations of mites and insects before and after the intervention were
      compared. RESULTS: A total of 428 dust samples from bed mats were collected, and
      the total infestation rate of mites and insects was 71.03%. There were 11 species
      of mites and insects identified, among which, the infestation rate of
      Dermatophagoides farinae (60.05%) was the highest, following by that of
      Liposcelis bostrychophilus (40.89%) . The infestation rates of Cheyletus
      malaccensis, Blattisocius sp. and Pyemotes sp. were 9.81%, 3.74% and 1.64%,
      respectively, and the above mites might cause dermatits. The infestation rates of
      mites and insects in dust samples from bed mats stored in indoor corner,
      wardrobe, bed bottom, and the balcony corner were 74.75%, 71.26%, 61.17%, and
      77.78%, respectively, and the differences among them were not statistically
      significant (chi2 = 7.030, P > 0.05) . The detectable rates of mites and insects
      in dust samples from bed mats with no cover, wrapped with cloth bags, and wrapped
      with plastic bags were 85.58%, 78.13%, and 14.29%, respectively, and the
      differences among them were statistically significant (chi2 = 164.303, P < 0.05)
      . After the intervention, both the infestation rates of mites and insects as well
      as the average density of mites were decreased, and the differences were
      statistically significant (chi2 = 45.615, t = 3.203, both P < 0.05) .
      CONCLUSIONS: The infestation rates of mites and insects in bed mats of the
      dormitories in the college of Wuhu City are high, and among all the species of
      mites infested, D. farina are preponderant. The intervention measures, such as
      prepacking bed mats by adequate sealing, soaking bed mats in the warm water,
      exposing the bed mats to the sunlight and cleaning indoor environment, have an
      inhibiting effect to the infestation of mites and insects.

PMID- 29469290
TI  - [Evaluation of Wondfo Rapid Diagnostic Kit for detecting Plasmodium ovale and
      analysis of influencing factors].
AB  - OBJECTIVE: To evaluate the Wondfo Rapid Diagnostic Kit (Pf-LDH/Pan -pLDH) for
      detecting Plasmodium ovale and analyze the influence of parasitaemia,
      concentration and polymorphism of pLDH on the performances. METHODS: A total of
      100 blood samples from P. ovale patients confirmed by PCR were detected with the
      Wondfo Rapid Diagnostic Kit according to the manufacturers'instructions. The
      parasitaemia was determined by the microscopic examination. The concentration of
      pLDH was measured by ELISA tests. The LDH gene of P. ovale was amplified by PCR
      and sequenced. The influence of these three factors on the positive rate was
      analyzed. RESULTS: The overall positive rate of Wondfo Rapid Diagnostic Kit was
      70.0% (70/100). The positive rate was 27.3% for the samples with parasitaemia <=
      500 parasites/MUl and reached 75.0%-75.4% when parasitaemia > 500 parasites/MUl.
      The positive rate was 6.7% for samples with a low pLDH concentration (A values <=
      0.100) and reached 95.1%-100% at a high pLDH concentration (A values > 0.100).
      The results of sequence analysis indicated that all the samples could be divided
      into 2 types, P. o. curtisi and P. o. wallikeri. The gene homology of LDH between
      2 types was 97%. There were 24 single nucleotide polymorphism (s) (SNPs) between
      2 types, while only 3 SNPs were non-synonymous mutations. The homology of LDH
      amino acid sequences between 2 types was 99%; only 3 amino acids were different.
      The positive rates for P. o. curtisi and P. o. wallikeri were 73.1% (38/52) and
      66.7% (32/48) respectively; there was no statistically significant difference (P
      > 0.05). CONCLUSIONS: The Wondfo Rapid Diagnostic Kit (Pf-LDH/Pan-pLDH) performs
      better than most of the similar products for the detection of P. ovale, and the
      positive rates are closely related to the parasitaemia and concentration of pLDH,
      while no related to the polymorphism of pLDH gene.

PMID- 29469292
TI  - [Prokaryotic expression and identification of secretory proteins and peripheral
      membrane proteins of Schistosoma japonicum].
AB  - OBJECTIVE: To prokaryotic express and identify the recombinant plasmids
      containing the genes or gene segments which coding secreted or peripheral
      membrane protein of Schistosoma japonicum. METHODS: A number of 28 pET32 (+)
      previous constructed recombinant plasmids containing these genes or segments were
      transferred into E. coli BL21 (DE3) strain for culture via the CaCl2
      transformation method, and then induced by IPTG for prokaryotic expression. Then,
      the bacteria were treated by broking the wall with ultrasonic, and the bacterial
      suspension, supernatant and precipitation were detected with 12% SDS-PAGE. The
      size and distribution of these target proteins were determined. Finally, the
      expression of the recombinant fusion protein was further identified by the
      protein microarray combined with anti-His tag fluorescent antibody. RESULTS:
      Under the inducing conditions of 0.1 mmol/L IPTG, 37 C, 200 r/min and 4 h, these
      fusion proteins were highly expressed in E. coli BL21 (DE3). The SDS-PAGE results
      showed all the 28 recombinant fusion proteins were expressed in different
      degrees, among which 2 were distributed in the supernatant, and the other 26 were
      distributed in precipitation, and the sizes of the fusion proteins were the same
      as that of prediction. The fluorescent signals of His antibody were successfully
      detected by confocal laser scanner. CONCLUSIONS: A series of recombinant plasmids
      containing genes or gene segments that coding secreted protein and peripheral
      membrane protein of S. japonicum have been successfully expressed by using an
      efficient prokaryotic expression system of E. coli. It has established a
      foundation for the high throughput immunoscreening of the vaccine candidates or
      diagnostic antigens of S.japonicum.

PMID- 29469293
TI  - [Cloning and characterization of beta-carbonic anhydrase, a potential drug target
      of Schistosoma japonicum].
AB  - OBJECTIVE: To express the beta carbonic anhydrase (beta-CA) of Schistosoma
      japonicum, and analyze its catalytic activity. METHODS: The cDNA and amino
      sequence which may encode beta-CA of S. japonicum were obtained by the
      bioinformatics-method, and then the cDNA sequence was cloned into prokaryotic
      expression vector pET-32a (+) and expressed. After examining by SDS-PAGE and
      Western blotting, the recombinant protein was purified by Ni-affinity
      chromatography and the catalytic activity was determined. RESULTS: The sequence
      Sjp_0056790.1 took on the conservative position of beta-CAs. The PCR and
      restriction enzyme digestion confirmed the construction of recombinant plasmid
      pET-32a (+) -SjaCA. SDS-PAGE and Western blotting analyses showed that the
      molecular weight of recombinant protein was about 38 kDa as expected, and it
      could be recognized by anti-His tag antibody. The catalytic activity determining
      revealed that the recombinant protein SjaCA owned the carbonic anhydrase
      activity. CONCLUSIONS: Sjp_0056790.1 encodes the beta-CA of S. japonicum, and the
      beta-CA with catalytic activity is successfully expressed, so it lays a
      foundation for the subsequent research of pharmacological inhibition, providing
      theoretic basis for searching and developing a new feasible anti-schistosome
      drug.

PMID- 29469294
TI  - [Sex bias in generation and functional phenotypes of peripheral T follicular
      helper cells in schistosomiasis japonica].
AB  - OBJECTIVE: To study the influence of sex on the generation and function of T
      follicular helper (Tfh) cells in the process of Schistosoma japonicum infection.
      METHODS: Totally 50 schistosomiasis patients were selected in the endemic areas
      of Chizhou City, Anhui Province, and totally 50 healthy people were selected in
      the non-endemic areas of Chizhou City as the controls. The peripheral bloods were
      collected from the above study subjects, and the human peripheral blood
      mononuclear cells from male/female schistosomiasis japonica patients or healthy
      controls were collected into the sodium heparin tubes and purified by Ficoll
      paque plus density gradient centrifugation. Then, the percentages of total Tfh
      cell, ICOS+ Tfh cells, and PD-1+ Tfh cells in the schistosomiasis male/female
      patients or healthy controls were evaluated by flow cytometry. RESULTS: Compared
      with the male and female healthy controls, the frequency of the total Tfh cells
      (Umale = 149.0, Ufemale = 39.5, both P < 0.01), the percentages of PD-1+ Tfh
      cells (tmale = 5.9, tfemale = 7.7, both P < 0.01) and ICOS+ Tfh cells (tmale =
      3.2, tfemale = 5.9, both P < 0.01) of the male and female patients with
      schistosomiasis increased, all the differences were statistically significant.
      The further analysis showed that the percentage of total Tfh cells (U = 187.5, P
      < 0.05), ICOS+ Tfh cells (t = 3.2, P < 0.05), and PD-1+ Tfh cells (t = 3.0, P <
      0.05) of the female patients were markedly higher than those of the male
      patients, all the differences were also statistically significant. CONCLUSIONS:
      Sex may be a crucial role in the generation and function of Tfh cells in the
      process of Schistosoma japonicum infection.

PMID- 29469295
TI  - [Meta regression analysis of five heavy metal biotoxicity effects on
      Caenorhabditis elegans].
AB  - OBJECTIVE: To evaluate five heavy metal biotoxicity effects on Caenorhabditis
      elegans with Meta regression analysis. METHODS: The data were collected from the
      following electronic databases:PubMed, Web of Science, EBSCO, the Chinese
      Biomedical Database, Chinese National Knowledge Infrastructure, Wan Fang
      (Chinese) Databases and so on, and all updated through January 2004 to December
      2014. A literature review was made on articles about Cd, Hg, Pb, As and Cr
      toxicity effects on C. elegans, and the data was extracted from figure
      information by Scan It software. A Meta regression model was built by stata12.0
      software, using toxicity indices such as the dependent variables, and different
      metals, concentrations, exposure time, and development stages of C. elegans as
      independent variables. RESULTS: The study articles asociated with heavy metal
      biotoxicity effects on C. elegans were selected out, 10 studies of Cu, 12 studies
      of Cr, 12 studies of Pb, 12 studies of Cd, 3 studies of As and 14 studies of Hg.
      The mortality of toxicities of 5 heavy metals on C. elegans ranked Hg > Pb > Cr>
      Cd>As; the biotoxicity of the indexes of body size based on development,
      generational time based on reproductive toxicity, body bend frequencies, and head
      thrash frequencies based on neurotoxicity ranked Hg > Pb > Cr > Cd; the
      biotoxicity ranked Hg > Pb > Cr> Cd>As by LC50 indexes of toxicities of 5 heavy
      metals on C. elegans. The sensitivity analysis proved that the Meta regression
      model was reliable. CONCLUSIONS: The biotoxicities on C. elegans of Hg and Pb are
      stronger than Cr, Cd and As.

PMID- 29469296
TI  - [Effect evaluation of water conservancy project with ditches managed against
      Oncomelania hupensis in Yunnan Province].
AB  - OBJECTIVE: To evaluate the effect of hydraulic schistosomiasis control project
      with ditches managed on Oncomelania hupensis snail control. METHODS: From 2009 to
      2011, the snail investigations and schistosomiasis surveillance were carried out
      in Dali City and Yongsheng County, two sites of national schistosomiasis
      surveillance. The history data of schistosomiasis control were collected and
      analyzed. RESULTS: At the harden sections of the water conservancy project with
      ditches managed in Shajing Village of Dali City, only one snail was found in 2010
      with the density of living snails of 0.004 snails/0.1 m2, while the densities of
      living snails were respectively 0.080, 0.002 snails/0.1 m2 and 0.007 snails/0.1
      m2 in unhardened sections of the project from 2009 to 2011. No snails were found
      in the harden sections of the water conservancy project with ditches managed in
      Gaojiacun Village of Yongsheng County, while the densities of living snails were
      respectively 0.040, 0.030 snails/0.1 m2 and 0.040 snails/0.1 m2 in unhardened
      sections of the project from 2009 to 2011. After the ditches were hardened, no
      infected snails were found from 2009 to 2011, and the appearance rate of frames
      with snails and density of living snails were both decreased, while they were
      both higher in unhardened ditches. CONCLUSIONS: The hydraulic schistosomiasis
      control project has obvious effect on control snails, but the maintain work
      should be strengthened after the project is completed.

PMID- 29469297
TI  - [Effect of control program of human intestinal parasitic diseases in Nanping
      City].
AB  - OBJECTIVE: To understand the epidemic status of human intestinal parasitic
      diseases and evaluate the effect of the control program in Nanping City, so as to
      provide an evidence for improving the disease control. METHODS: The villages were
      selected by the stratified cluster sampling method and the residents in these
      villages were surveyed for human intestinal parasitic diseases, and kindergartens
      were also selected and the children in these kindergartens were surveyed for
      Enterobius vermicularis infection. RESULTS: In 2007, before the control program,
      9 851 residents of Nanping City were surveyed, with the parasitic infection rate
      of 9.10% (896 infection cases), and the infection rate of E. vermicularis of
      children was 18.56% (328/1 767). From 2011 to 2014, when the control program was
      performed, 4 679 residents were surveyed, with the infection rate of 4.06% (190
      infection cases), and the infection rate of E. vermicularis of children was 3.87%
      (33/853). After the control program was launched, the infection rates of human
      intestinal parasites were decreased. The overall parasitic infection rate and
      hookworm infection rate showed increasing trends by age (chi2 = 49.03 and 53.58
      respectively, both P < 0.01). CONCLUSIONS: The infection situation of human
      intestinal parasites is decreased after the implementation of the control program
      but the infection rate is still at a high level, and the control work should be
      strengthened.

PMID- 29469298
TI  - [Analysis of epidemic situation of malaria in Longlin Various Nationalities
      Autonomous County in Guangxi from 1951 to 2014].
AB  - OBJECTIVE: To analyze the data of epidemic situation of malaria in Longlin
      Various Nationalities Autonomous County, Guangxi Zhuang Autonomous Region, China
      from 1951 to 2014 and discuss the distribution characteristics and epidemic law,
      so as to provide the evidences for developing the prevention and control
      strategies of the disease. METHODS: The data about the epidemic situation of
      malaria in Longlin Various Nationalities Autonomous County were collected and
      analyzed statistically with Excel 2007. RESULTS: Totally 93 460 malaria cases
      were reported from 1951 to 2014 in the county. There were two morbidity peaks of
      malaria during this period, namely 1950s and 1970s, and the annual average
      incidence rates were 3 237.94/100 000 and 1 572.12/100 000, respectively, but it
      began to flatten after 1980s. Before 2000, the local cases were the main type,
      however, there were no endogenous cases since 2008. In 1950s, falciparum malaria
      was the main type of the disease, and the cases with falciparum malaria, tertian
      malaria and quartan malaria were accounted for 45.01% (2 392/5 314), 33.72% (1
      792/5 314) and 19.55% (1 039/5 314), respectively; while in 1960s, the proportion
      of cases with tertian malaria increased, that of the cases with quartan malaria
      decreased, and there were no quartan malaria cases reported since 1980s. There
      were imported malaria cases reported since 1990s, and a total of 51 cases were
      found in this period, among which, 50 cases (98.04%) were tertian malaria, and
      the main infection sources were the cases from epidemic areas in other provinces
      of China. After 2000, the imported malaria cases with falciparum malaria
      increased, with a proportion of 60.00% (21/35), and the infection sources were
      mainly from Africa and Southeast Asia. CONCLUSIONS: The local endemic of malaria
      in Longlin Various Nationalities Autonomous County has been effectively
      controlled, but the situation of imported malaria is still severe in this county.
      Therefore, strengthening the surveillance of floating population, especially the
      workers backing from overseas, is still the key of malaria prevention and control
      in the future.

PMID- 29469299
TI  - [Analysis of endemic situation of schistosomiasis in Jingzhou City from 2004 to
      2014].
AB  - OBJECTIVE: To analyze the change of endemic situation of schistosomiasis in
      Jingzhou City of Hubei Province, so as to provide evidence for the development of
      future control strategy. METHODS: The data of endemic situation of
      schistosomiasis and the implementation of integrated control measures were
      collected and analyzed in the 9 counties (districts, cities) of Jing-zhou City
      from 2004 to 2014. RESULTS: The endemic situation of schistosomiasis appeared a
      decline year by year since 2004. The prevalence of human Schistosoma japonicum
      infection was 0.40% in 2014, which was reduced by 95.72% as compared to that in
      2004, and the fitting exponential equation was y = 11.067e-0.240x. The incidence
      of acute schistosomiasis reduced to less than 0.5 per 100 000 in 2007. No acute
      infection was found since 2010, and no emergency epidemics occurred for
      successive 9 years. It was estimated that there were currently 22 547 people
      infected with S. japonicum, which reduced by 85.87% in relative to 2004. The
      prevalence of cattle S. japonicum infection reduced to 0 in 2014, with a 100%
      reduction as compared to that in 2004, and the fitting exponential equation was y
      = 15.69e-0.339 8x. The actual Oncomelania hupensis snail area was 31 084.00 hm2,
      which reduced of 1931.21 hm2 as compared to that in 2004, with a 5.91% reduction,
      and no schistosome-infected snails were found since 2012. Both human and animal
      schistosome infections reduced to less than 1% in all administrative villages in
      2013. CONCLUSIONS: The implementation of the key schistosomiasis program and
      whole-county promotion and province-ministry joint integrated control program
      results in effective control of schistosomiasis in Jingzhou City. However,
      further control programs are required to consolidate the achievements, interrupt
      and eliminate schistosomiasis.

PMID- 29469300
TI  - [Impact of self-efficacy on behaviors of contacting infested water among middle
      school students in Hubei Province].
AB  - OBJECTIVE: To explore the impact of self-efficacy on the behavior of contacting
      schistosome cercarial infested water among middle school students. METHODS: In
      the transmission control area and endemic control area of the schistosomiasis
      endemic regions in Hubei Province, a total of 3 204 middle school students were
      selected through the stratified cluster random sampling method and investigated
      by questionnaires. RESULTS: The incidence rates of contacting infested water with
      Oncomelania hupensis snails during the past 3 and 12 months among the middle
      school students were 11.4% (364/3 204) and 14.8% (474/3 204) respectively, while
      those of contacting indefinite infested water during the past 3 and 12 months
      were 23.8% (762/3 204) and 28.0% (898/3 204) respectively. The awareness rate of
      schistosomiasis prevention and control knowledge was 82.1% (2 631/3 204). There
      were "knowledge-practice separation"in the prevention and control of
      schistosomiasis among the middle school students. The correlation analysis and
      Logistic regression analysis showed that the self-efficacy of schistosomiasis
      protective behavior of middle school students was a protective factor for
      contacting with infested water, with the adjusted odds ratio values of 0.882,
      0.886, 0.914 and 0.927. CONCLUSIONS: Self-efficacy of schistosomiasis protective
      behavior is a protective factor for contacting with infested water among middle
      school students, and improving their self-efficacy may be an effective strategy
      to settle the problem of"knowledge-practice separation".

PMID- 29469301
TI  - [Preparation of anti-SEA egg yolk immunoglobulin and its preliminary
      application].
AB  - OBJECTIVE: To prepare the egg yolk immunoglobulin (IgY) against soluble egg
      antigen (SEA) of Schistosoma japonicum, and explore its feasibility for
      schistosomiasis screening in endemic areas. METHODS: The urine samples of
      indirect haemagglutination test (IHA) positives from endemic areas and healthy
      people from non-endemic areas were collected. The Anti-SEA IgY was obtained
      through immunization by subcutaneous injection of SEA into Laihang hen, and its
      molecular weight was determined by SDS polyacrylamide gel electrophoresis (SDS
      PAGE) . The circulating soluble egg antigen (CSEA) in the urine of IHA positives
      and healthy people were detected by ELISA-double antibody sandwich method with
      the Anti-SEA IgY as the capture antibody. RESULTS: Anti-SEA IgY was prepared and
      purified successfully. Totally 48 urine samples of IHA positives were detected by
      ELISA and 26 of them were CSEA positives (54.17%); 10 urine samples of healthy
      people were detected, and all of them were negative. CONCLUSIONS: The CSEA in
      human urine can be detected effectively by ELISA based on IgY. As a convenient
      and atraumatic method, it could be applied in schistosomiasis screening.

PMID- 29469302
TI  - [Survey and morphological observation of Lepidoglyphus destructor in college
      canteens].
AB  - OBJECTIVE: To understand the breeding and morphology of Lepidoglyphus destructor
      in college canteens in south Anhui Province. METHODS: The powder and rice on the
      floor around dough makers, flour bags and rice bags in college canteens were
      collected and observed under a microscope. RESULTS: Totally 108 samples were
      collected, and Acaroid mites were found in 101 of them with a detection rate of
      93.52%. Totally 1 527 mites were found with an average breeding density of
      1.41/g. Under the light microscope observed, the L. destructor's four pairs of
      legs were tapering from tarsus. The back setae were stiff and the ventral setae
      were smooth and relatively short. The internal vertical seta was longer than the
      top of the chelicera. Dorsal seta d3, d4, lateral seta l3 and sacral inner hair
      sai were the longest. The female mites were bigger than the male ones, and had
      more anal seta than male ones. The genital fold of female mites almost connected
      together, and the front-end had a crescent shaped plate cover. CONCLUSIONS: The
      breeding of Acaroid mites in college canteens is serious, and therefore,
      effective measures should be taken to prevent and control it.

PMID- 29469303
TI  - [Investigation of Lardoglyphus konoi (Astigmata) breeding in stored
      Solenognathus].
AB  - OBJECTIVE: To investigate the mites breeding in stored Solenognathus. METHODS:
      Solenognathus was collected from a Chinese medicine shop in Wuhu City, and mites
      were isolated and identified under a microscope. RESULTS: Totally 256 mites were
      isolated from 500 g Solenognathus, and four species were found, including 219
      Lardoglyphus konoi, 12 Tyrophagus longior, 21 Tyrophagus putrescentiae and 4
      Euroglyphus maynei. The breeding density of L. konoi was 0.438/g. CONCLUSIONS:
      There are mites breeding in the stored Solenognathus, and the most mites are L.
      konoi. Effective measures should be taken to prevent and control it.

PMID- 29469304
TI  - [Countermeasures and experiences of schistosomiasis control work under new
      situation of Shengzhou City].
AB  - OBJECTIVE: To summarize the experience of Oncomelania hupensis snail control work
      and explore more effective snail control strategy under the new situation.
      METHODS: The data of former snail control work and strategies were collected and
      analyzed in Shengzhou City from 1995 to 2015. RESULTS: The snail area was
      effectively compressed in recent years, and it was decreased by 46.61% and 26.50%
      in 2014 and 2015 respectively compared with that in the last year. CONCLUSIONS:
      To consolidate the snail control achievements, the government should pay more
      attention to the schistosomiasis control work and establish a targeted effective
      long-term strategy.

PMID- 29469305
TI  - [Monitoring situation of eliminating malaria in Shaoguan City from 2001 to 2014].
AB  - OBJECTIVE: To analyze the malaria monitoring situation in Shaoguan City from 2001
      to 2014, and evaluate the efficacy of the malaria control and prevention work, so
      as to provide the evidence for formulating the effective eliminating malaria
      measures. METHODS: The microscopic examination monitoring points of "four-fever"
      patients were established in medical institutions at all levels in Shaoguan City
      from 2001 to 2014, and the fever patients were examined by microscopy and the
      active case monitoring was performed. By using the epidemiology method, the
      malaria incidence and classification of cases were described and analyzed
      statistically. RESULTS: From 2001 to 2014, 91 381 "four-fever" patients were
      monitored and 22 malaria patients were found with the average positive rate of
      0.02%. Among the 22 malaria patients, 20 were imported (90.91%) and 2 were local
      cases (9.09%). The local patients were infected with Plasmodium vivax, and among
      the imported patients, 16 patients were infected with P. vivax, 2 infected with
      P. falciparum and 2 infected with P. ovale. No local infection cases were found
      since 2006. All the patients were timely treated and no second generation cases
      were found. From 2011 to 2014, 2 611 person-times were actively investigated in 7
      counties (city) and no malaria patients were found. CONCLUSIONS: In Shaoguan
      City, there are remarkable achievements in the malaria prevention and control
      work. However, there are still imported cases in recent years, and therefore, the
      monitoring system should be perfected and the effective monitoring should be
      strengthened.

PMID- 29469306
TI  - [Investigation on Toxoplasma gondii infection in childbearing age and pregnant
      women in Langfang City, Hebei Province].
AB  - OBJECTIVE: To understand the status of Toxoplasma gondii (TOX) infection in
      childbearing age and pregnant women in Langfang City, Hebei Province. METHODS:
      Totally 276 pregnant women and 462 childbearing age women were investigated to
      detect the levels of TOX antibodies with ELISA from March 2013 to June 2015.
      RESULTS: The positive rates of Tox-IgG and Tox-IgM were 11.59% (32/276) and 5.43%
      (15/276) respectively in the pregnant women, and the rates were 8.87% (41/462)
      and 0.87% (4/462) respectively in the childbearing age women, and the positive
      rate of Tox-IgM of the pregnant women was higher than that of the childbearing
      age women (chi2 =14.32, P<0.01). The positive rate of the right age pregnant
      women (<=35 years) was 10.09% (22/218), and that of the advanced age pregnant
      woman (>35 years) was 25.86% (15/58), and the difference was statistically
      significant (chi2 = 9.81, P<0.01). The positive rate of women close contacting
      with pet was 18.67% (14/75), and the rate of women not close contacting with pet
      was 10.26% (68/663), and there was a statistically significant difference between
      them (chi2 =4.82, P<0.05). CONCLUSIONS: The positive rates of Toxoplasma
      antibodies are high in childbearing age and pregnant women in Langfang City,
      Hebei Province, and most of them are silent infection, and the recent infection
      rate is higher in the latter than that in the former.

PMID- 29469307
TI  - [Evaluation of end-term effectiveness of medium-and-long-term programme for
      schistosomiasis control in Fanchang County, Anhui Province].
AB  - OBJECTIVE: To evaluate the end-term effectiveness of the medium-and-long-term
      programme for prevention and control of schistosomiasis in Fanchang County, Anhui
      Province. METHODS: The epidemiological data of schistosomiasis were collected and
      analyzed in Fanchang County from 2004 to 2014. The end-term effectiveness of the
      programme was observed and evaluated. RESULTS: From 2004 to 2014, 1 938
      schistosomiasis patients and 64 256 persons with the history of infested water
      contact were treated. Totally 12 cattle-times of schistosome infected cattle and
      2 745 cattle-times of cattle with the history of infested water contact were
      treated. The area with snails controlled by molluscicides was 7 758.1 hm2, and
      the area with snails controlled by environmental modification was 36.0 hm2. The
      integrated control measures were carried out in all of the endemic villages with
      human infection rate being higher than 1%. Up to 2014, the infection rates of
      human and cattle, and the incidence rate of acute schistosomiasis were reduced to
      0.27%, 0 and 0, respectively; the area with snails reduced to 103.20 hm2; the
      densities of both living snails and infected snails showed a declining trend in
      general. CONCLUSIONS: The effect of the integrated strategies of schistosomiasis
      control is remarkable, and the whole county reached the criteria of transmission
      controlled of schistosomiasis.

PMID- 29469308
TI  - [Endemic situation of schistosomiasis in a surveillance site of river and lake
      regions in Haining City, 2012-2014].
AB  - OBJECTIVE: To understand the endemic dynamics and situation of schistosomiasis in
      a provincial surveillance site in Haining City, Zhejiang Province. METHODS: The
      Oncomelania hupensis snail status, schistosome infection situations of permanent
      residents and floating population in Qinmin Village, Haining City were monitored
      from 2012 to 2014 according to The Surveillance Programs of Schistosomiasis in
      Surveillance Sites of Zhejiang Province. RESULTS: Totally 600 permanent residents
      were examined from 2012 to 2014. The total positive rate of the serum antibody
      against Schistosoma japonicum was 3.17% (19/600). The rates in each year were
      2.50% (5/200), 0 (0/200), and 7.00% (14/200), respectively, and the rate in 2014
      were significantly higher than that in 2013 (chi2 = 14.508, P < 0.01), but no
      positives were found in the fecal examination. Totally 1 591 floating population
      were involved in the surveillance, the positive rate of serum antibody were 0.94%
      (15/1 591). The rates in active surveillance and passive surveillance were 0.92%
      (14/1 521) and 1.43% (1/70), respectively, and there were no statistically
      significant difference between them (chi2 = 1.659, P > 0.05). The positive rates
      of serum antibody among each year were 1.50% (8/534), 0.56% (3/531), and 0.76%
      (4/526), respectively, and the difference was not statistically significant (chi2
      = 2.752, P >0.05), but no positives were found in the fecal examination. The
      snail surveillance showed that there were no environments with infected snails
      and imported snails. CONCLUSIONS: There exist the infection sources of
      schistosomiasis in Haining City. Therefore, we should be on high alert for the
      potential of local endemic of the disease. Meanwhile, we still should strengthen
      the snail surveillance as well as the infection surveillance among the floating
      population.

PMID- 29469309
TI  - [Clinical analysis of 17 cases of paragonimiasis].
AB  - OBJECTIVE: To investigate the clinical features, diagnosis and treatment of
      paragonimiasis, so as to improve the prevention and treatment of it. METHODS: The
      clinical data of paragonimiasis patients were collected and retrospectively
      analyzed. RESULTS: Totally 17 patients were diagnosed as paragonimiasis and the
      main clinical features of 11 patients were cough, chest pain and fever, and the
      pleural effusion was found in 13 cases. Peripheral blood eosinophil percentages
      of all patients were significantly increased, and the detections of antibody IgG
      againstParagonimus parasite of ELISA method were positive in all patients. All
      the patients were cured after praziquantel treatment and no recurrence found in
      the follow-up visit. CONCLUSIONS: The clinical features of paragonimiasis
      patients are diverse, and pleural effusion is quite common in imaging
      examinations. The eosinophil percentages and antibody detections have important
      values for the diagnosis of paragonimiasis. Praziquantel is an effective medicine
      in the treatment.

PMID- 29469310
TI  - [Progress of researches on diagnostic methods of current Schistosoma infection].
AB  - Now schistosomiasis is still a serious zoonosis which affects human health and
      hinders the economy development in endemic areas. Accurate diagnosis of the
      infection of Schistosoma is very significant in reducing hazards to human health
      and controlling the epidemic of schistosomiasis. This review summarizes recent
      advances in the laboratory diagnostic methods for current schistosome infection
      (including pathogenic, immunologic and molecular biologic methods) so as to
      provide the reference for prevention and control of schistosomiasis in the field.

PMID- 29469311
TI  - [Impact of new trend of ecological environment changes on growth, reproduction
      and diffusion of Oncomelania hupensis].
AB  - Oncomelania hupensis is the only intermediate host of Schistosoma japonicum, and
      the growth, reproduction and distribution of O.hupensis play an important role in
      schistosomiasis prevalence and transmission. This article reviews the influence
      of the new trend of ecological environment changes on the growth, reproduction
      and diffusion of the snails.

PMID- 29469312
TI  - [Epidemiological characteristics of canine Echinococcus infection in Qinghai
      Tibet Plateau of China].
AB  - The Qinghai-Tibet Plateau is known as one of the highest endemic areas of
      echinococcosis. However, the dog infection rates of Echinococcus granulosus in
      the plateau regions were similar to other non-Tibetan areas with the high
      endemic, and most of the rates were below 40%. The infected dogs with E.
      multilocularis were ubiquitous in Ganzi Prefecture of Sichuan Province and
      Qinghai Province where many survey data were done and available, which was much
      different from those in non-Ti-betan areas where the geographical distribution of
      dogs infected with E. multilocularis was sporadic. The total infection rates of
      Echinococcus in dogs kept stable from 1983 to 2009 in Ganzi Prefecture of Sichuan
      Province and did not show much variation from 2000 to 2014 in Qinghai Province as
      well. Since 2006, the national comprehensive prevention and control strategy and
      measures against echinococcosis have been launched in China, and significant
      progress has been made. In the endemic Tibetan area of Sichuan, the general
      Echinococcus infection rates in dogs were 28.10%, 15.87%, 19.22%, 3.28% and 1.11%
      from 2009 to 2013, respectively, and the Echinococcus coproantigen-positive rate
      in Gannan Prefecture of Gansu Province and parts of Qing-hai Province also
      decreased. This paper reviews the literature on the characteristics of dog
      infections in the Qinghai-Tibetan Plateau, so as to provide useful information to
      support echinococcosis control and prevention there.

PMID- 29469313
TI  - [Endemic situation trend of schistosomiasis in Guichi District of Chizhou City,
      Anhui Province, 1991-2011].
AB  - OBJECTIVE: To understand the epidemical patterns of schistosomiasis in Guichi
      District of Chizhou City, Anhui Province, in order to provide the reference for
      schistosomiasis control. METHODS: The annual data of schistosomiasis endemic
      situation in Guichi District from 1991 to 2011 were collected. The descriptive
      analysis was first conducted to describe the changes of schistosomiasis in local
      residents and the status of Oncomelania hupensis. An autoregressive integrated
      moving average (ARIMA) model was applied to fit and predict the tendency of
      schistosomiasis incidence in this region. RESULTS: The human morbidity increased
      with the increasing of the areas with snail habitats (P < 0.05), and four peaks
      (in 1992, 1995, 2005, 2008) were detected. The difference of the area with snails
      among different types of snail habitats was statistically significant (F =
      256.79, P < 0.05). ARIMA (1, 1, 1) was determined to be the optimal model for
      analyzing the morbidity of schistosomiasis, and the short-term forecast of the
      morbidity in Guichi District from 2012 to 2015 showed that the predicted values
      were 0.017%, 0.007%, 0.012%, and 0.010%, respectively. CONCLUSIONS: The endemic
      situation of schistosomiasis in Guichi District is controlled relatively well in
      the past two decades. However, the surveillance in the lake and marshland regions
      should be strengthened continuously to prevent the rebounding of the
      schistosomiasis endemic situation.

PMID- 29469314
TI  - [Epidemiological characteristics of malaria in Liaoning Province from 1951 to
      2014].
AB  - OBJECTIVE: To explore the epidemiological characteristics of malaria in Liaoning
      Province from 1951 to 2014, so as to provide the evidence for further control of
      the disease. METHODS: The data of registered malaria cases in Liaoning Province
      from 1951 to 2014 were collected and analyzed with epidemiological methods.
      RESULTS: From 1951 to 2014, there were reported malaria cases each year. The
      peaks of incidence were in 1953, 1962 and 1973, the incidence rates were
      136.67/100 000, 256.81/100 000 and 35.89/100 000 respectively and the numbers of
      patients were 27 862, 65 460 and 11 523, respectively. From 1977 to 2014, the
      incidence rates were all less than 1/100 000. From 1951 to 1980, the occupations
      of patients were mainly farmers, and from 1981 to 2014 were mainly workers,
      farmers and exported laborers. CONCLUSIONS: The malaria endemic situation in
      Liaoning Province experienced the periods from outbreaks to basically
      elimination, and the long-term surveillance will be the further working emphasis.

PMID- 29469315
TI  - [Study on cyfluthrin resistance and its mechanisms of Anopheles sinensis in
      Nanchang frontierport].
AB  - OBJECTIVE: To study the cyfluthrin resistance and potential mechanisms of
      Anopheles sinensis in Nanchang Chang-bei International Airport, Nanchang City,
      Jiangxi Province. METHODS: The resistance levels of the local An. sinensis were
      detected by WHO drug resistance bioassay. During the bioassay, the dying
      mosquitos were classed as sensitive mosquitos, and the survival ones were classed
      as resistant mosquitos. The P450 monooxygenase activity and glutathione S
      transferase activity were detected and compared between the two groups. At the
      same time, the death time of each sensitive mosquito was recorded, and the
      correlations between the death time and the P450 monooxygenase activity and
      glutathione S-transferase activity were analyzed, respectively. RESULTS: The
      bioassay mortality of the local An. sinensis was 59.5%. The differences of the
      P450 monooxygenase activities among the resistant mosquitos, sensitive mosquitos
      and laboratory sensitive mosquitos had statistical significances (F =151.89, P <
      0.01), the resistant mosquitos > sensitive mosquitos > laboratory sensitive
      mosquitos. The differences of glutathione s-transferase activities among the
      three groups had no statistical significance (F = 0.72, P = 0.49). There existed
      positive correlation between the mosquito death time and the P450 monooxygenase
      activity, and the regression equation was y = 79.479 +1.512x with the correlation
      coefficient of 0.88, while there was no correlation between the mosquito death
      time and the glutathione S-transferaseactivity. CONCLUSIONS: The An. sinensis in
      Nanchang Changbei International Airport has been resistant to cyfluthrin, and the
      promotion of P450 monooxygenase activity maybe one of the reasons for the
      resistance.

PMID- 29469316
TI  - [Clinical features of imported schistosomiasis mansoni in Beijing City:a report
      of 6 cases].
AB  - OBJECTIVE: To analyze the clinical features of 6 patients with imported
      schistosomiasis mansoni, including the epidemic history, clinical manifestations,
      laboratory tests and therapeutic effect, so as to provide references for
      improving the levels of diagnosis and treatment of physicians. METHODS: The
      clinical data of 6 patients with imported schistosomiasis mansoni from January
      2009 to July 2016 were collected and analyzed. RESULTS: All the 6 imported
      patients with schistosomiasis mansoni had a clear history of cercarial infested
      water exposure. The main manifestations were continuous fever and eosinophilia.
      Three (50%) patients were accompanied with diarrhea. Anti-Schistosoma japonicum
      IgG antibody were cross positive in 2 (33.3%) patients, while live eggs of S.
      mansoni were explored in intestinal mucosa specimens of all the patients.
      CD3+CD8+ T cell ratio was decreased significantly but B cell ratio was elevated
      in all the patients, and the main immunoglobulin of the patients was IgG.
      Hydroperitoneum and splenomegaly signs were discovered by abdominal
      ultrasonography in 16.6% (1/6) of the patients. Multiple liver nodules and wall
      thickening of rectum and sigmoid colon were revealed by pelvic MR scan in 16.6%
      (1/6) of the patients. Colitis was found in all the patients, and 66.6% (4/6) of
      the patients were combined with multiple colonic ulcers by the electronic
      colonoscopy examination. Chronic inflammation and eosinophil infiltration were
      found in all the patients by rectum pathology. All 6 patients were cured with
      chemotherapy named praziquantel. CONCLUSIONS: Comprehensive analysis of clinical
      data including epidemiological history, specific manifestations, laboratory tests
      and intestinal mucosa pathology may be benefit of the management of
      schistosomiasis mansoni.

PMID- 29469317
TI  - [Analysis of results of Assessment on National Parasitic Disease Control and
      Prevention Techniques in 2015].
AB  - OBJECTIVE: To assess the theoretical knowledge and practical skills of parasitic
      diseases among technicians from disease control and prevention institutions.
      METHODS: The Assessment on National Parasitic Disease Control and Prevention
      Techniques was organized in September, 2015. Together, 124 subjects from disease
      control and prevention institutions at province, prefecture or county levels in
      31 provinces joined the assessment. A database was built consisting of subjects'
      basic information and assessment scores. Statistical analysis was used to analyze
      the scores by gender, age, professional title, institutions and places of
      participants. RESULTS: The average total score of all the subjects was 123.3,
      with a passing rate of 57.3%. The average scores of male subjects (48 subjects)
      and female subjects (76 subjects) were 125.9 and 121.7 respectively; the average
      scores of the subjects aged under 30 years (57 subjects), between 30 and 40 years
      (61 subjects) and above 40 years (6 subjects) were 119.6, 128.1 and 111.2
      respectively; the average scores of persons with junior (94 subjects),
      intermediate (28 subjects) and senior (2 subjects) professional titles were
      119.2, 135.9 and 140.5 respectively. The average theoretical assessment score of
      all the subjects was 61.9, with a passing rate of 62.9%. The average practical
      skill assessment score of all the subjects was 61.4, with a passing rate of
      58.1%. CONCLUSIONS: The theoretical assessment results range widely. The
      theoretical knowledge results of technicians from disease control and prevention
      institutions are low in general. Therefore, the specific training based on daily
      work needs to be enhanced.

PMID- 29469318
TI  - [Optimization and comparison of extraction methods of mitochondrial DNA of
      Oncomelania hupensis].
AB  - OBJECTIVE: To optimize the extraction methods of mitochondrial genome DNA (mtDNA)
      of Oncomelania hupen- sis. METHODS: The pyrolysis, protein K variable-temperature
      digestion and high-concentration potassium acetate purification were applied to
      optimize the high-concentration-salt precipitation method, and then the optimized
      method was compared with two common extraction methods, the sucrose density
      gradient centrifugation method and traditional high-concentration-salt
      precipitation method. The mtDNA samples were identified by using
      spectrophotometry, agarose gel electrophoresis and the amplification products of
      COX1. The nuclear DNA contamination was tested by the amplification products of
      ITS. RESULTS: The concentration and yield of the improved method was
      significantly higher than those of the traditional method (F = 3 032.65, 10
      185.00, both P < 0.01). The mtDNA samples extracted were essentially free of
      nuclear DNA and protein, meeting PCR, sequence analysis and other molecular
      biology research requirements. CONCLUSIONS: The improved high-concentration-salt
      precipitation method for isolating mtDNA is simple, and it has high yield and low
      cost. The extracted mtDNA can meet relevant analysis requirements.

PMID- 29469319
TI  - [Temporal and spatial distribution of Schistosoma infection of population and its
      risk factors in Eastern Dongting Lake area in 2012 and 2014].
AB  - OBJECTIVE: To investigate the temporal and spatial distribution of Schistosoma
      infection of population and its risk factors in Eastern Dongting Lake area in
      2012 and 2014, so as to provide the reference for formulating effective
      intervention measures. METHODS: Junshan District was selected as a study field in
      Eastern Dongting Lake area. The method of spatial autocorrelation analysis was
      applied to analyze the change of spatial distribution of Schistosoma infection in
      Junshan District in 2012 and 2014. The spatial regression model was fitted to
      detect the risk factors for human infection. RESULTS: The livestock infection
      rate in 2013 was lower than that in 2011. The average infection rate of
      schistosome was reduced to 0.55% in 2014. The spatial autocorrelation existed on
      the distribution of schistosomiasis in Junshan District in both 2012 and 2014 and
      4 high incidence villages were identified. The results of the spatial error model
      showed that the prevalence of human infection was positively correlated with the
      infection rate of the livestock and the area of the susceptible environment in
      2012. The spatial lag model showed that the prevalence of human schistosomiasis
      was positively correlated with the area of the susceptible environment, but not
      with the infection rate of livestock. CONCLUSIONS: The measures involving grazing
      prohibition and phasing out cattle and sheep are remarkably effective and should
      continue on the basis of the current spatial distribution of schistosomiasis in
      this area.

PMID- 29469320
TI  - [Investigation on malaria knowledge and demands on related training for CDC staff
      in Qinghai Province, China].
AB  - OBJECTIVE: To investigate the malaria knowledge of CDC staff and their demands on
      related training in malaria non-endemic areas, so as to provide the reference for
      planning the appropriate curriculum. METHODS: All the participants who were the
      staff of county CDCs all over Qinghai Province and attended the provincial
      training workshop were surveyed. A self-administered questionnaire survey was
      carried out and the data was statistically analyzed. RESULTS: A total of 115
      participants were involved in this survey. They were mostly (85.21%) from county
      CDCs. The general knowledge of malaria among the respondents was well, and the
      average rate of correct answers was 70.35%. However, the answers to the general
      knowledge of malaria and anti-malaria treatment were not well enough. The rates
      of correct answers were 61.96% and 48.99% respectively. The differences among the
      groups of job title ranking, department of working and level of CDC were not
      significant (F = 0.13-2.02, all P > 0.05). The number of correct answers was
      significantly increased after the training course. The average score after the
      training was 79.20+/-15.16 while the pre-training score was 70.34+/-17.46 (t =
      3.86, P < 0.05), especially in the answers to general malaria knowledge and
      malaria surveillance and response (t = 4.30, 4.97, both P < 0.05). The general
      knowledge of malaria was considered as the most need of training as 80% of the
      respondents voted "Yes", according to the demand analysis. There was no
      significant difference among the different groups (F = 0.61-3.11, both P > 0.05).
      CONCLUSIONS: The malaria knowledge is well mastered by the staff of CDCs in
      Qinghai Province, and the further training courses are requested and addressed in
      the target areas such as general malaria knowledge, anti-malaria treatment,
      malaria surveillance and response.

PMID- 29469321
TI  - [Identification of a myeloid differentiation factor 88 (MyD88) in Oncomelania
      hupensis against Schistosoma japonicum infection].
AB  - OBJECTIVE: To identify a myeloid differentiation factor 88 (MyD88) in Oncomelania
      hupensis, and characterize the role of MyD88 against Schistosoma japonicum
      infection. METHODS: The complete cDNA of MyD88 in O. hupensis was obtained by
      using rapid amplification of cDNA ends (RACE), and homologues sequences and
      conserved domains were aligned and the structure of MyD88 was predicted either. A
      phylogenetic tree of MyD88 was further constructed with other species. In
      addition, the mRNA expression level of O. hupensis MyD88 before and after S.
      japonicum infection was investigated by real-time quantitative PCR (RT-qPCR).
      RESULTS: The cDNA of O. hupensis MyD88 consisted of 1 406 bp open reading frame
      (ORF), encoding 468 amino acid residues, which contained death domain and
      Toll/interlrukin-1 receptor (TIR) domain, the typical features of MyD88 family
      proteins. The predicted amino acid sequence of O. hupensis MyD88 shared 38%-52%
      identity with other mollusc. O. hupensis MyD88 was phylogenetically closeted to
      Biomphalaria glabrata MyD88. The O. hupensis MyD88 existed in all selected
      tissues and expressed highly in hemocyte, up-regulated after S. japonicum
      infection in all selected tissues except cephalopodium, especially higher in
      whole snail and hemocyte. CONCLUSIONS: MyD88-dependent signaling pathway is
      present in O. hupensis and plays an important role in innate immune response
      against S. japonicum infection.

PMID- 29469322
TI  - [Risk assessment of secondary transmission induced by imported malaria in Jiangxi
      Province].
AB  - OBJECTIVE: To assess the risk of secondary transmission induced by imported
      malaria in Jiangxi Province, so as to provide the evidence for adjustment of
      malaria surveillance strategies in the key groups and areas. METHODS: The Delphi
      method was used to establish the secondary transmission risk indicator system and
      the weight of each index was obtained. The data of malaria prevalence, vector
      distribution and intervention capacity were collected in 100 counties of Jiangxi
      Province from 2012 to 2015. The transmission potential index (TPI), intervention
      capacity index (ICI), and malaria risk index (MRI) were calculated for each
      county. The risk map was drawn with GIS software. RESULTS: The top ten counties
      with highly potential risk indicators were Linchuan District (2.131), Xinzhou
      District (1.609), Jiujiang County (1.404), Zhanggong District (1.365), Fengcheng
      City (1.225), Qingshanhu District (1.184), Yudu County (1.171), Dingnan County
      (1.018), Xunyang District (1.015) and Zhushan District (1.006). The high risk
      areas were mainly distributed in the regions of the capitals of their prefectures
      and in counties with more floating population. CONCLUSIONS: There are the risk of
      the secondary transmission induced by imported malaria in Jiangxi Province. The
      high risk of the secondary transmission is shown in the areas with more floating
      population and weaker intervention capacity.

PMID- 29469323
TI  - [Molecular epidemiology of Cryptosporidium infection in infants with diarrhea in
      Wuhan City].
AB  - OBJECTIVE: To understand the prevalence of Cryptosporidium infection in diarrhea
      infants under 2 years old in Wuhan City, so as to provide the epidemiological
      evidence for the prevention and treatment of cryptosporidiosis. METHODS: The
      fecal samples from infants under 2 years old with diarrhea were collected in
      Hubei General Hospital and Central South Hospital in Wuhan City, Hubei Province
      from August 2014 to July 2015. The fecal samples were stored in 2.5% potassium
      dichromate at 4 C after filtered. The DNA was extracted from the fecal pellets
      with the phenol-chloroform method. The Cryptosporidium species were detected by a
      nested PCR assay targeting the SSU rRNA gene of the parasite. All the positive
      PCR products were sequenced on ABI 3100 automated sequencer, and the amplified
      sequences were compared to homologous sequences in the NCBI database by using the
      Basic Local Alignment Search Tool (BLAST). Phylogenetic analyses were performed
      by using the software MEGA (version 4.0) based on the Neighbour-Joining method.
      RESULTS: The human stool specimens (n = 298) were screened for the presence of
      Cryptosporidium by nested PCR. The infection rate of Cryptosporidium was 3.02%
      (9/298). The infection rate of Cryptosporidium was 5.93% (7/118) in the infants
      between 1-2 years old, and the infection rate was 1.11% (2/180) in the infants
      under 1 year old, and there was a significant difference between the two groups
      (chi2 = 4.13, P < 0.05). The nine samples which were positive by nested PCR were
      successfully sequenced and compared with the reference sequences in GenBank. The
      results revealed the nine positive specimens were all infected with C. parvum,
      and two of them were co-infected with C. hominis. Neighbor-joining trees were
      constructed from the aligned partial SSU rRNA sequences of these nine isolates,
      and in the SSU rRNA locus, the nine isolates were grouped with C. parvum.
      CONCLUSIONS: There exists Cryptosporidium infection in the infants under 2 years
      old with diarrhea in Wuhan City, and the main species of Cryptosporidium is C.
      parvum.

PMID- 29469324
TI  - [Changes of liver fibrosis-related miRNAs induced by soluble egg antigen of
      Schistosoma japonicum].
AB  - OBJECTIVE: To investigate the expression of miRNA associated with hepatic
      fibrosis induced by Schistosoma japonicum soluble egg antigen stimulation in
      mouse hepatocytes (AML12), so as to lay the foundation for clarifying the
      mechanism of schistosome infection leading to hepatic fibrosis. METHODS: The
      expressions of miR-122, miR-182, miR-23b, miR27b and KSRP in AML12 cells treated
      with SEA were measured by q-PCR. KSRP protein in cell lyses was measured by
      Western blotting. AML12 cells were transfected with miR-27b precursor or anti-miR
      27b for 24 h, then q-PCR was adopted to determine KSRP mRNA, and KSRP protein was
      detected by Western blotting. RESULTS: The expressions of miR-182, miR-23b and
      miR27b were decreased and miR-122 was increased in AML12 cells following SEA
      treatment (all P < 0.05). An increase of mRNA and protein of KSRP expression was
      also observed in AML12 cells after SEA stimulation (both P < 0.05). In addition,
      KSRP mRNA expression was not changed significantly in AML12 cells transfected
      with anti-miR-27b or miR-27b precursor, and miR27b precursor reduced KSRP protein
      expression as compared with the control. In contrast, the expression of KSRP
      protein was increased in the anti-miR-27b group and decreased in the miR-27b
      precursor group. CONCLUSIONS: After the stimulation of SEA, the expressions of a
      variety of liver fibrosis-related miRNAs and KSRP change in murine hepatocytes,
      including miR-27b. And miR-27b can regulate the expression of KSRP. These
      findings might lay a foundation for further study on the molecular mechanism of
      fibrosis induced by schistosome infection.

PMID- 29469325
TI  - [Evaluation on human resource allocation in certain national institute of
      parasitic diseases in ten years].
AB  - OBJECTIVE: To evaluate the human resource in a national institute of parasitic
      diseases from 2007 to 2016, so as to provide a reference for the construction of
      a well-crafted human resource of national parasitic diseases control and
      prevention. METHODS: The basic information of the staff in the national institute
      of parasitic diseases was investigated and a related database was established to
      analyze the quantity and structure of the human resource allocation in 10 years
      through the annual statistics each year. RESULTS: The number of staff in the
      institute increased by 6.25% in 2016 compared with that in 2007, and 43.32% of
      the staff were under 35 years old. In 2016, 59.36% of the staff had a master
      degree or a higher level degree, and 37.97% of the staff had senior technical
      titles. The difference value of the inflows and outflows was 3.21%. CONCLUSIONS:
      The change of the structure and quality of human resource in this institute has a
      good tendency in the past ten years. The organization should optimize the human
      resource allocation and improve its capacity in disease control and prevention to
      broaden the methods of talent introduction and control the brain drain problem.

PMID- 29469326
TI  - [Present situation of health education work in schistosomiasis control and
      evaluation on its effectiveness in Hubei Province].
AB  - OBJECTIVE: To understand the present situation and requirements of health
      education in schistosomiasis control in Hubei Province, so as to improve the
      health education to the targeted people. METHODS: Through the questionnaire
      survey and field investigation, the data of the present situation and
      requirements of health education in schistosomiasis control were collected in 24
      counties (cities) of Hubei Province, and these data included the related
      institution structure of health education, basic information of personnel,
      equipment, funds, and health education working form. All the data collected were
      analyzed and evaluated. RESULTS: Among the 24 counties, there were 12 independent
      departments of health education, accounting for 50%. In terms of the basic
      information of the health education staff, the youngest person was 34 years old
      and the eldest was 58 years old, and the mean age was 46.55+/- 6.9 years. For the
      formal school education of the staff, 5 had senior high school or below education
      (20.8%), 16 had college education (66.7%), 3 had bachelor degree or above
      (12.5%). There were 10 counties (41.70%) with the special funds for health
      education work but there were 3 counties (12.50%) without the special funds.
      CONCLUSIONS: The effectiveness of health education work in schistosomiasis
      control is remarkable, but there are still deficiencies in professional staff and
      funds in Hubei Province.

PMID- 29469327
TI  - [Infection situation of intestinal nematodes and knowledge about prevention and
      control of intestinal nematodiasis in Jingjiang City].
AB  - OBJECTIVE: To investigate the infection situation of intestinal nematodes and
      knowledge about the prevention and control of intestinal nematodiasis, so as to
      explore the effective control measures in Jingjiang City. METHODS: The towns
      where more floating people lived were randomly selected and the infection
      situation of intestinal nematodes was investigated with KatoKatz method, and the
      residents'awareness of the prevention and control of nematodiasis was surveyed
      with questionnaires. RESULTS: From 2013 to 2015, totally 4 555 local residents
      and 2 278 floating people were investigated in Jingjiang City. The infection rate
      of intestinal nematodes was 0.29% (13 cases) in the local people, while the rate
      was 0.75% (17 cases) in the floating people, and the difference was significant
      (chi2 = 7.380, P < 0.01). The differences of the intestinal nematode infection
      rates between sexes in both local residents and floating people were not
      significant (chi2 = 0.010, 0.048, both P > 0.05). The awareness rate of
      intestinal nematodiasis prevention and control of the local residents was
      significantly higher than that of the floating people (chi2 = 9.649-164.533, all
      P < 0.01). CONCLUSIONS: The floating people is the focus of intestinal
      nematodiasis control, and the health education of ancylostomiasis control should
      be strengthened in Jingjiang City.

PMID- 29469328
TI  - [Surveillance with sentinel mice in key water areas of schistosomiasis endemic
      regions in Yunnan Province, 2015].
AB  - OBJECTIVE: To carry out the surveillance with sentinel mice in the key water
      areas of schistosomiasis endemic regions in Yunnan Province, so as to establish
      and perfect the surveillance and forecast system of schistosomiasis. METHODS: Six
      villages of three counties with schistosomiasis heavy endemic status were
      selected as the survey points. Then, the surveillance and forecast with the
      sentinel mice were carried out in the key water areas in the survey points. The
      recovered sentinel mice were dissected in laboratory, and their serum antibodies
      against schistosome were detected. Meanwhile, the suspicious infested water
      contacts of the residents and livestock in the surveillance sites were
      investigated, and the endemic data of schistosomiasis in the survey points in
      recent 3 years were collected and analyzed. RESULTS: Totally 282 sentinel mice
      were placed in the water area, 252 were recovered, with a recovery rate of
      90.78%, and 8 mice were dead, with a mortality rate of 3.13%. The number of mice
      with schistosome egg granuloma and adult worm detected were both 0, and the worm
      burden and the positive rate of serum antibodies against schistosome were both 0,
      too. The persons who contacted with the suspicious infested water were mainly
      villagers and students by harvesting and playing. The Oncomelania hupensis snail
      areas, the infection rates of residents and livestock were obviously declined in
      recent 3 years. CONCLUSIONS: There are no positive sentinel mice found in the key
      water areas of the surveillance sites in Yunnan Province, which suggests that the
      schistosome infection risk of residents and livestock is low. However, the
      comprehensive control measures, surveillance and forecast with sentinel mice in
      the key water areas of schistosomiasis endemic regions still should be
      strengthened.

PMID- 29469329
TI  - [Effect of network training on clinicians'knowledge of malaria diagnosis and
      treatment in Yunnan Province].
AB  - OBJECTIVE: To introduce the application of the network training on clinicians'
      knowledge of malaria diagnosis and treatment in Yunnan Province, and evaluate its
      effect. METHODS: Through the platform Yiboshi (www.yiboshi.com), the medical and
      health personnel at the units of provincial, prefectural, county levels and 25
      townships of 25 border counties were trained on the knowledge of malaria
      diagnosis, treatment, prevention and control, and the effects were evaluated by
      examinations, questionnaires and interviews. RESULTS: Totally 7 152 participants
      were trained, the average participation, completion and pass rates of the
      training were 95.26%, 98.55% and 97.30%, respectively. The trainees mainly
      learned malaria control knowledge from 3 aspects, namely policy of malaria
      elimination, malaria epidemiology, malaria diagnosis and treatment. The
      questionnaires showed that 95.94% of the participants considered that their
      theoretical and technical levels improved, 97.30% were interested in the training
      content, 93.24% recognized the arrangement of the training time was reasonable,
      and 91.89% were satisfied with the service of the platform. CONCLUSIONS: The
      network training on knowledge of malaria diagnosis and treatment in Yunnan
      Province has achieved good effect. The network training meets the need of
      training a large number of clinicians in the malaria elimination and post
      elimination stage.

PMID- 29469330
TI  - [Serological survey of Toxoplasma gondii infection in women with adverse
      pregnancy outcomes in Longhua region, Hebei Province].
AB  - OBJECTIVE: To understand the status of Toxoplasma gondii infection in women with
      adverse pregnancy outcomes in Longhua region, Hebei Province. METHODS: A total of
      393 women with adverse pregnancy outcomes were chosen as respondents in the
      Longhua County Maternal and Child Health Care Center between January 2013 and
      June 2016 and were divided into an acute infection group, a previous infection
      group, and an active infection group according to the test results. Totally 256
      women without adverse pregnancy outcomes were selected as a control group. IgM
      and IgG antibodies to T. gondii were detected by using ELISA in each group. The
      risk factors of T. gondii infection were surveyed by questionnaires. RESULTS: The
      T. gondii infection rate of the women with adverse pregnancy outcomes was 27.23%
      (107/393), which was significantly higher than 8.20% (21/ 256) in the control
      group (chi2 = 35.46, P<0.01). The rates of acute infection, previous infection,
      active infection in the women with adverse pregnancy outcomes were 6.87%
      (27/393), 18.58% (73/393), and 2.54% (10/393) respectively, which was
      significantly higher than those[1.17% (3/256), 7.03% (18/256), 0 (0/256) ]in the
      control group (chi2 = 11.43, 17.15, 7.90 respectively, P<0.01). The ratios of the
      career in contact with raw meat, feeding pets (dog and cat), tasting raw meat,
      chopping board regardless of uncooked or cooked food, frequently eating rinsing
      boiler or barbecue, frequently eating outside of the women with T. gondii
      infection were significantly higher than those of the women without T. gondii
      infection (chi2 =12.08, 29.23, 8.55, 13.41, 7.28, 6.06 respectively, P < 0.01 or
      0.05). CONCLUSIONS: T. gondii infection could lead to serious adverse pregnancy
      outcomes. Therefore, to avoid contacting with pets, not eating undercooked food,
      and strengthening personal health protection are the important keys to avoid T.
      gondii infection.

PMID- 29469331
TI  - [Knowledge, attitude and practice related to schistosomiasis control among rural
      residents in Wanjiang River region after a flood].
AB  - OBJECTIVE: To investigate the status of knowledge, attitude and behavior of
      schistosomiasis control of rural residents in Wanjiang River region after a
      flood, so as to provide the reference for targeted health education. METHODS: The
      multistage sampling was applied to select the respondents in rural residents in
      Wanjiang River region, and the self-designed questionnaire was used to
      investigate the current situation of knowledge, attitude and behavior of
      schistosomiasis prevention and control of the rural residents. RESULTS: The total
      awareness rate of knowledge about the prevention and control of schistosomiasis
      was 47.92%. The age, education, family income, relatives and friends with medical
      background, and health education significantly influenced the awareness rate
      (chi2 = 12.76, 89.19, 18.19, 50.83 and 92.60 respectively, all P < 0.05). The
      accuracy rates of attitude and behavior in schistosomiasis control were 62.89%
      and 52.37% respectively. CONCLUSIONS: The awareness rate of knowledge about the
      prevention and control of schistosomiasis, and the accuracy rates of attitude and
      behavior in schistosomiasis control of the rural residents in Wanjiang River
      region are all inefficient, and therefore, the targeted health education should
      be strengthened to decrease the risk of schistosomiasis transmission.

PMID- 29469332
TI  - [Analysis of antibody titer value of IHA in 135 acute schistosomiasis patients].
AB  - OBJECTIVE: To analyze the antibody titer value of indirect haemagglutination test
      (IHA) in 135 confirmed acute schistosomiasis patients, so as to provide the
      evidence for improving the diagnosis and treatment of acute schistosomiasis.
      METHODS: A total of 135 acute schistosomiasis inpatients were selected from 2001
      to 2006. They all received the IHA antibody titer detection, and the correlation
      among the age, incubation period, and hospitalization days was calculated.
      RESULTS: The antibody titers of IHA were higher than 1:320 in all the cases. The
      percentages of 1:640, 1:1 280, 1:2 560, 1:5 120 and 1:10 240 were 1.48%, 28.15%,
      35.56%, 20.00%, and 14.81% respectively. The mean age was (47.70 +/- 14.58)
      years, average incubation period was (38.03 +/- 4.59) days and mean hospital stay
      time was (15.08 +/- 3.79) days. The antibody titer value had no correlation with
      the age distribution (r = 0.109, P > 0.05). There was a negatively correlation
      between the antibody titer value and incubation period, (r = -0.558, P <0.01),
      there was a positive correlation between the antibody titer value and
      hospitalization time (r = 0.791, P < 0.01), and there were significant
      differences among different groups (F = 17.07, 64.53, both P < 0.01).
      CONCLUSIONS: The antibody titer of acute schistosomiasis cases detected by IHA is
      1:640 and above. There is no correlation between the antibody titer value and
      age, but the antibody titer value is higher, the incubation period is shorter and
      hospitalization time is longer.

PMID- 29469333
TI  - [Preliminary investigation of Suidasia nesbitti breeding status in ground dust
      flour in Qiqihaer City].
AB  - OBJECTIVE: To investigate the Suidasia nesbitti breeding status in the ground
      dust flour collected in Qiqihaer City. METHODS: Totally, 16 aliquots of ground
      dust flour were respectively collected from a college canteen and 15 households
      in Qiqihaer City. Then 10 g dust flour was taken from individual sample for
      isolation of the mites that were made of slide specimen, and the mites were
      identified and classified under a microscope. RESULTS: Acaroid mites were found
      in 15 of the 16 aliquots of samples (detection rate being 93.8%), and 7 species,
      belonging to 6 genera under 3 families, were identified. A total of 561 heads of
      mites were isolated from 160 g samples, with an average breeding density of 3.51
      heads/g. The most breeding mite was associated with S. nesbitti. CONCLUSIONS:
      Various species of mites are breeding in the ground dust flour in Qiqihaer City,
      and S. nesbitti occurs the most. These findings indicate that effective measures
      should be taken to prevent and control the harm associated with acaroid mite
      contamination.

PMID- 29469334
TI  - [Evaluation of ELISA kit for detection of serum specific IgG antibodies against
      Taenia solium in diagnosis of human cysticercosis].
AB  - OBJECTIVE: To evaluate the ELISA kit for detection of IgG antibodies against
      Taenia solium cysticercus in humans, so as to provide a reference for its
      application in clinical practice. METHODS: The sera collected from the patients
      with neurocysticercosis, echinococcosis, taeniasis and healthy people,
      respectively, were checked by ELISA for specific IgG antibodies against T. solium
      cysticercus, as described in the instruction of the kit. RESULTS: Of the 30
      patients with neurocysticercosis at active stage, 28 showed seropositive
      reaction, indicating a sensitivity of 93.33%. There were no positive reactions in
      the 100 healthy people. Two of the 42 persons with taeniasis were seropositive
      with an infection rate of 4.76%. Forty-one of the 60 persons with echinococcosis
      showed positive reactions, suggesting that the cross reaction rate of the kit
      with echinococcosis was 68.33%. CONCLUSIONS: The assessed ELISA kit has a
      reasonably high sensitivity but a poor specificity, and the cross reaction rate
      with echinococcosis is very high. It is urgent to improve the sensitivity and
      specificity of the diagnostic kit for detection of T.solium cysticercosis in
      China.

PMID- 29469335
TI  - [Application of CroelDRAW software in drawing sketch map of schistosomiasis
      control].
AB  - OBJECTIVE: To improve the information level of schistosomiasis control by using
      the related functions of CorelDRAW software. METHODS: Combining with the
      requirement of schistosomiasis control, the sketch map was drawn according to the
      linear element drawing, the geometric drawing, the color rendering and the text
      adding. RESULTS: The schistosomiasis epidemic sketch map and the Oncomelania
      hupensis snail distribution sketch map at all levels were produced in CorelDRAW
      software. CONCLUSIONS: The sketch map drawing in CorelDRAW software is beautiful
      and standardizing, and it can improve the level of information management.

PMID- 29469336
TI  - [Analysis of academic impact of publications from National Institute of Parasitic
      Diseases, Chinese Center for Disease Control and Prevention based on SCIE
      database in recent five years].
AB  - OBJECTIVE: To describe the academic impact of publications from National
      Institute of Parasitic Diseases (NIPD), Chinese Center for Disease Control and
      Prevention, so as to give the quantity evidence for scientific research decision
      making. METHODS: The SCIE papers of NIPD published from 2011-2015 were searched
      and statistically analyzed. The number of published papers, citation frequencies,
      h-index, and funding resources were analyzed. The academic impact of the
      institute was assessed according to these data. RESULTS: A total of 361 papers
      were published by NIPD, and the quantity increased year by year. The majority
      type is original articles. The total citations were 1 641 times, the average
      citation per paper was 5.19 and h-index was 17. The majority of these papers were
      published in foreign professional periodicals, whose impact factors were between
      1.194 and 6.751. The major resources of NIPD were from China, and NIPD also had
      good collaborations with institutions in US and Switzerland. In China and Asia,
      NIPD led the research in the field of parasitology and tropical medicine.
      CONCLUSIONS: The quantity and quality of annual published papers of NIPD are on
      the rise. However, NIPD lagged behind the leading institutions in the world.

PMID- 29469337
TI  - [Efficacy of repeated application of praziquantel in treatment of hepatic
      fibrosis due to schistosomiasis].
AB  - OBJECTIVE: To evaluate the efficacy of repeated application of praziquantel in
      the treatment of hepatic fibrosis due to schistosomiasis. METHODS: A total of 60
      patients with schistosomiasis hepatic fibrosis (clinically diagnosed cases) were
      selected and divide into a treatment group and control group randomly, with 30
      cases each group. The patients in the treatment group were given praziquantel[30
      mg/ (kg.d) for 2 days]each year for three consecutive years, on the basis of the
      conventional liver protection therapy and symptomatic treatment. The patients in
      the control group were given the conventional liver protection therapy and
      symptomatic treatment. All the treatment duration was 36 months. The clinical
      symptoms were observed, and the liver function, and the levels of HA, LN, IV-C,
      and PCIII were detected in the two groups before and after the treatment.
      RESULTS: The clinical symptoms and liver function improved, and the HA, LN, IV-C,
      PCIII levels were decreased in the treatment group with varying degrees, and the
      total effective rate was 93% (26/28). The total effective rate in the control
      group was 60% (16/27). There was a significant difference between the two groups
      in the total effective rate (P < 0.05). CONCLUSIONS: The repeated application of
      praziquantel has a better therapeutic efficacy in the treatment of hepatic
      fibrosis due to schistosomiasis.

PMID- 29469338
TI  - [Epidemiological analysis of malaria situation in Wenzhou City in 2015].
AB  - OBJECTIVE: To analyze the characteristics of malaria prevalence in Wenzhou City,
      so as to provide the evidence for improving the comprehensive control of malaria.
      METHODS: The epidemiological data of malaria cases in Wenzhou City in 2015 were
      collected and analyzed with the descriptive epidemiological methods. RESULTS:
      Totally 24 imported malaria cases were reported in Wenzhou City in 2015 with the
      incidence of 0.26 per 100 000 and no case was dead. Plasmodium vivax, P.
      falciparum, and P. ovale were identified in 1 (4.17%), 20 (83.33%), and 3
      (12.50%) cases, respectively. The cases reported in Rui'an, Cangnan and Lucheng
      counties/districts accounted for 70.83% (17/24) of the total cases in Wenzhou
      City. The cases were mostly concentrated in male young adults and 23 cases
      (95.83%) were imported from Africa. CONCLUSIONS: Malaria epidemic situation in
      Wenzhou City is relatively stable and no local malaria cases were reported in
      2015. However, the control work of imported malaria should be strengthened.

PMID- 29469339
TI  - [Research progress of control techniques on Oncomelania hupensis].
AB  - Oncomelania hupensis is the only intermediate host of Schistosoma japonicum. The
      elimination of Oncomelania snails is the key technique step for schistosomiasis
      control. This paper summarizes the progress of the techniques of snail control,
      including the methods of ecology engineering, biology, molluscicides and the
      study on novel molluscicides, and reviews their features. In addition, this paper
      explores the appropriate approach to control the snails.

PMID- 29469340
TI  - [Research progress of Babesia rhoptry associated proteins].
AB  - Babesia parasites are obligate intracellular apicomplexan protozoa and important
      pathogens causing babesiosis of humans and animals. They have conserved
      subcellular structures and invasion mechanism. Rhoptry-associated proteins, which
      are released into the host cell, are considered to be the key molecules of
      invasion and replication of parasites in the host cell and are immunosuppressive
      factors of the host cell mediated immunity in the stage of parasitophorous
      vacuole (PV) formation. The knowledge about rhoptry-associated proteins has made
      a great progress with the development of genomics and proteomics, so we review
      the research progress in rhoptry-associated proteins of different Babesia
      including Babesia bovis, B. ovine, B. gibsoni, B. bigemina and B. orientalis,
      etc.

PMID- 29469341
TI  - [One case report of Ancylostoma duodenale parasitized in hepatic flexure of
      colon].
AB  - This paper reports a case of Ancylostoma duodenale parasitized in the hepatic
      flexure of colon and the case was misdiagnosed at the beginning. The causes of
      misdiagnosis are analyzed and the laboratory examination methods of hookworm are
      summarized.

PMID- 29469342
TI  - [Precision control is essential to achieve the goal of schistosomiasis
      elimination in China. Summary of the Second Forum on Schistosomiasis Control in
      China].
AB  - The Second Forum on Schistosomiasis Control in China was successfully held in
      Jiangsu Institute of Parasitic Diseases during the period between 21th and 23th,
      September, 2017. Based on the topic "Implementation of precision control to
      accelerate the progress towards schistosomiasis elimination", the forum discussed
      three macro problems pertaining to how to improve the theory and policy of
      precision control during the progress towards schistosomiasis elimination in
      China, and six technical problems regarding how to achieve more precise
      management of the residual sources of infections and more precise monitoring of
      transmission risk. Finally, a consensus was achieved that precision control is
      essential to achieve the goal of schistosomiasis elimination in China.

PMID- 29469343
TI  - [Interpretation of Diagnostic Criteria for Clonorchiasis].
AB  - Clonorchis sinensis infection is carcinogenic to human, which results in
      cholangiocarcinoma, confirmed by the World Health Organization. An investigation
      in 2005 indicated that the standardized C. sinensis infection rate was 0.58%,
      with 12 490 000 infected people estimated in the clonorchiasis endemic areas in
      China. In the world, 80% of C. sinensis infected people were distributed in
      China. Diagnostic Criteria for Clonorchiasis (WS309-2009) was compiled by the ex
      Ministry of Health of the People's Republic of China and it was issued and
      implemented in March 13, 2009. The Diagnostic Criteria for Clonorchiasis is
      composed of six chapters, including the Range of Application, Terms and
      Definitions, Diagnostic Basis, Diagnostic Principle, Diagnostic Standard, and
      Differential Diagnosis. Three informative appendices (etiology, epidemiology,
      clinical manifestation; enzyme-linked immunosorbent assay; differential
      diagnosis) and one normative appendix (laboratory examination) are appended. The
      Criteria provides the technical reference for diagnosis of clonorchiasis in
      medical institutions and disease control institutions. Combined with the current
      epidemic situation of clonorchiasis in China, this paper interprets the main
      contents of the Diagnostic Criteria for Clonorchiasis (WS309-2009), so as to
      promote its learning and implementing.

PMID- 29469344
TI  - [Interpretation of Diagnostic Criteria for Kala-azar].
AB  - Kala-azar was once transmitted in the northern area of the Yangtze River in
      China, including 16 provinces (cities or autonomous regions). Through the great
      continuing prevention and control effort, this disease has been effectively
      controlled in the most of endemic areas. However, because the epidemic factors of
      the disease are complex, this disease still transmits or sporadically occurs in
      the western part of China, including 60 counties of Xinjiang, Gansu, Sichuan,
      Inner Mongolia, Shanxi, and Shaanxi provinces (autonomous regions). Following the
      Management Measures for Health Criteria, the Diagnostic Criteria for Kala-azar
      (WS 258-2006) was compiled by the ex-Ministry of Health of the People's Republic
      of China and it was issued in April 7, 2006 and implemented in December 1, 2006.
      The Criteria consists of six parts, including the application range, terms and
      definitions, diagnostic principle, diagnostic standard, and differential
      diagnosis. Two informative appendices (epidemiology and differential diagnosis)
      and two normative appendices (immune-detection and etiological examination) are
      attached. The Criteria provides the technical reference for diagnosis of kala
      azar in medical institutions and disease control institutions. Combined with the
      current epidemic situation of kala-azar in China, this paper interprets the main
      contents of the Diagnostic Criteria for Kala-azar (WS 258-2006), so as to promote
      its learning and implementing.

PMID- 29469345
TI  - [Study on distribution status of Oncomelania hupensis - intermediate host of
      Schistosoma japonicum in Jiangxi Province I Analysis of distribution of O.
      hupensis in Poyang Lake area].
AB  - OBJECTIVE: To grasp the distribution status of Oncomelania hupensis snails in
      Poyang Lake area, so as to provide the evidence for formulating and adjusting the
      schistosomiasis prevention and control strategy in lake areas. METHODS: The
      vector grid was created and sampled randomly by 200 m * 200 m in the spatial
      database of grassland, and the distribution of snails was investigated in the
      selected grid by using the method of mechanical sampling by 50 m * 50 m. At the
      same time, the elevation of investigation points was extracted based on the
      topographic map of Poyang Lake. RESULTS: Totally 949 and 210 investigation points
      were collected from the south and north of Poyang Lake areas, accounting for
      3.04% and 3.21% of all the investigation points in the respective region. The
      number of investigation points, the appearance rate of snail frame, and the
      average density of alive snails were 15 231, 8.15%, and 0.463/0.1 m2,
      respectively. The elevation of snail distribution area of the south and north
      Poyang Lake areas were 11-16 m and 9-16 m respectively. The elevation of
      concentrated snail belts of the south Poyang Lake area were 12-13 m and 15-16 m,
      and the elevation of concentrated snail belts of the north Poyang Lake area was
      12-14 m. CONCLUSIONS: The distribution of snails is in the range of 9-16 m. The
      suitable habitats of snail breeding are moving from the south Poyang Lake area to
      the north Poyang Lake area, and from high elevation to low elevation. In the
      future, the schistosomiasis prevention and control measures could be formulated
      based on the geographical characteristics of current snail distribution in order
      to consolidate the achievements of schistosomiasis control.

PMID- 29469346
TI  - [Strategy and effect of Oncomelania hupensis snail control in inside-embankment
      areas in Junshan District, Hunan Province from 1998 to 2017].
AB  - OBJECTIVE: To explore the strategy and countermeasures of Oncomelania hupensis
      snail control and evaluate the effect in inside-embankment areas of lake-type
      schistosomiasis endemic area, for providing the effective method for controlling
      and interrupting the schistosomiasis transmission. METHODS: The data of
      schistosomiasis epidemic and its control and prevention were collected in Junshan
      District, Hunan Province, and the effect of snail control countermeasures were
      evaluated and the trend of indexes of snails was drafted in the inside-embankment
      areas of Junshan District, Hunan Province from 1998 to 2007. RESULTS: The area
      with snails in the inside embankment areas of Junshan District decreased by
      98.43%, from 1 496.66 hm2 in 1998 to 23.48 hm2 in 2017. The occurrence rate and
      average density of of living snails decreased from 20.61% and 0.45 snail/0.1 m2
      in 2003 to 2.06% and 0.03 snail/0.1 m2 in 2017. The highest area with schistosome
      infected snails was found in 2001 and the total area was 79.36 hm2, however, no
      infected snails were found since 2007. The total fiscal investment for
      schistosomiasis prevention and control was 398.857 million RMB in Junshan
      District, including molluscicide (81.770 9 million RMB) and environment reform
      (213.5 million RMB) respectively. CONCLUSIONS: The comprehensive measures, mainly
      including the combination of molluscicide and environment reform have gotten a
      significant effect in snail control and elimination in the inside-embankment
      areas, but the snail surveillance still need to be strengthened in the historic
      areas with snails.

PMID- 29469347
TI  - [MRI findings of cerebral schistosomiasis in acute stage:establishment of
      experimental model of acute cerebral schistosomiasis with rabbits].
AB  - OBJECTIVE: To establish an experimental model of acute cerebral schistosomiasis
      japonica and explore the MRI manifestations of acute cerebral schistosomiasis.
      METHODS: Rabbits were divided into 3 groups with 10 rabbits in each group. The
      rabbits in the experimental group were directly injected with suspension fluid of
      Schistosoma japonicum eggs (0.9 mg, 1 ml) by the cranial drilling method, those
      in the negative control group were given saline (1 ml) by the same method above
      mentioned, and those in the blank control group were not given any treatment.
      Antibiotic was given to the first two groups after the operation. The clinical
      manifestations of the 3 groups were observed, and the magnetic resonance imaging
      (MRI) was performed in 30 days post-operation, and then the brain tissues were
      taken for pathological examinations. RESULTS: All the rabbits in the experimental
      group exhibited inappetence, various neurological symptoms including hemiplegia,
      and weight loss after the operation; while those in the negative control group
      showed inappetence in 3 days after the operation, and 1 week later, the symptom
      disappeared; there were no adverse reactions in the blank control group. MRI of
      the experimental group showed nodular or patchy enhancement on T1WI enhancement,
      brain edema, abnormal ventricular dilatation, and needle augmentation. SWI
      displayed hypointense in the abnormal enhanced nodules and flaky hypointense on
      the operation brain. In the negative control group, 2 rabbits showed abnormal
      enhancement of the needle canal, and 1 showed mild dilatation of the ventricle.
      The blank control group showed normal manifestations. The pathological
      examinations showed abnormal appearances in 10 rabbits of the experimental group,
      including 6 with S. japonicum egg granuloma nodules, nonspecific granuloma
      nodules coexisted with perivascular inflammation; no granuloma nodules were found
      in the negative control group, but 2 rabbits showed vascular inflammation; the
      blank control group showed the normal brain tissue. CONCLUSIONS: An experimental
      model of acute cerebral schistosomiasis is successfully established in rabbits by
      intracranial injection of schistosome eggs. The MRI examination combined with the
      clinical manifestations can improve the accuracy of early diagnosis of cerebral
      schistosomiasis.

PMID- 29469348
TI  - [Study on risk assessing indicator system after schistosomiasis transmission
      interruption in Wuxi City].
AB  - OBJECTIVE: To establish a risk assessing indicator system after the transmission
      interruption of schistosomiasis in Wuxi City, so as to provide evidences for
      formulating strategies on schistosomiasis control and prevention. METHODS: A
      primary risk assessing indicator system was established based on the literature
      review. Alternative indicators were scored and screened to establish a final
      indicator system through two rounds of Delphy method and the related normalized
      weights and combined weights were also calculated. RESULTS: The risk assessing
      indicator system was established through two rounds of expert consultation
      including 3 first grade indicators and 15 second grade indicators. Among the
      first grade indicators, the normalized weights of natural environment, key
      populations and social environment were 0.370 6, 0.292 9 and 0.336 5,
      respectively. Among the second grade indicators, the migrant population accounted
      for the highest combined weight of 0.125 2 compared to domestic animal of 0.037
      1. The authority degree among the first grade indicators was between 0.91 and
      0.93, while the authority degree among the second grade indicators was between
      0.79 and 0.92. CONCLUSIONS: The scientific and authoritative risk assessing
      indicator system after the transmission interruption of schistosomiasis is
      established, which provides the evidences for risk assessment on schistosomiasis
      transmission in Wuxi City.

PMID- 29469349
TI  - [Study on interventions based on urban - rural integration system construction to
      consolidate achievements of schistosomiasis control in hilly schistosomiasis
      endemic areas].
AB  - OBJECTIVE: To explore the effectiveness of comprehensive schistosomiasis control
      interventions based on urban-rural integration system construction to carry out
      the schistosomiasis control in hilly schistosomiasis endemic areas, so as to
      offer a new mode to consolidate the achievements of schistosomiasis control in
      the new situation. METHODS: Shouan Town and Changqiu Township in Pujiang County
      in hilly schistosomiasis endemic regions were selected as demonstration areas.
      The comprehensive schistosomiasis control interventions based on urban-rural
      integration system construction were implemented, including the land
      consolidation, centralized residence and so on. The effectiveness the
      interventions was evaluated. RESULTS: In Shouan Town and Changqiu Township, the
      transformed environments with Oncomelania hupensis snail habitats were 1 330.61
      hm2 and 1 456.84 hm2, the areas with snails decreased from 94.31 hm2 and 83.00
      hm2 in 2000 to both 0 in 2015, the positive rates of serological tests for
      schistosomiasis decreased from 11.8% and 7.53% in 2000 to 1.01% and 1.86% in
      2015, and the positive rates of parasitological tests decreased from 0.18% and
      0.15% in 2000 to both 0 in 2015 respectively. The numbers of cattle decreased
      from 358 and 368 in 2000 to 4 and 6 in 2015 respectively. In 2000, the
      schistosome infection rates of cattle were 3.63% and 6.51% in Shouan Town and
      Changqiu Township respectively, and from 2004, no infected cattle were found.
      CONCLUSIONS: The comprehensive schistosomiasis control interventions based on
      urban-rural integration system construction can decrease the schistosome
      infection rate and area with snails effectively, providing a new mode for
      schistosomiasis elimination.

PMID- 29469350
TI  - [Knowledge, attitude and practice on schistosomiasis control of chronic
      schistosomiasis patients in Poyang Lake area, Nanchang City].
AB  - OBJECTIVE: To understand the present situation of the chronic schistosomiasis
      patients' knowledge, attitude and practice on schistosomiasis control in Nanchang
      City. METHODS: The knowledge, attitude and values on schistosomiasis control of
      523 chronic schistosomiasis patients in Nanchang County, Jinxian County and
      Xinjian District in the Poyang Lake District were investigated with
      questionnaires. And the accuracy rates of the knowledge, attitude and practice
      among the patient groups of different counties, genders, age groups, occupations
      and educational levels were analyzed. RESULTS: The accuracy rates of the
      knowledge, attitude and practice of patients on schistosomiasis control were
      95.76%, 82.80%, and 81.73% in Nanchang County; 91.37%, 93.32%, and 76.48% in
      Jinxian County; 88.25%, 67.56%, and 49.40% in Xinjian District. In the accuracy
      rates of knowledge, attitude and practice, the differences among the three
      counties (districts) were statistically significant (chi2 = 57.511-301.378, all P
      < 0.05) . CONCLUSIONS: The accuracy rates of chronic schistosomiasis patients'
      attitude and practice on schistosomiasis control in Nanchang City remain low.
      Therefore, the intensity of attitude and practice intervention should be
      strengthened in the Poyang Lake District in order to enhance the self-protection
      awareness of the patients.

PMID- 29469351
TI  - [Survey of schistosomiasis KAP and influencing factors of behaviors among
      residents in Jiangsu Province].
AB  - OBJECTIVE: To understand the schistosomiasis control knowledge, attitude, and
      practice (KAP), and influencing factors of behaviors among residents in Jiangsu
      Province, so as to provide the evidence for making effective health education and
      health promotion models. METHODS: The probability proportionate to size sampling
      (PPS) and multi-stage sampling methods were adopted to sample the research
      objects. A questionnaire survey of schistosomiasis control KAP was conducted in
      the residents of 16 to 69 years old in schistosomiasis endemic areas of Jiangsu
      Province, and the results were statistically analyzed. RESULTS: The total
      awareness rate of the participants was 95.98% for schistosomiasis control
      knowledge. The correct rates of attitude and practice were 89.06% and 77.43%,
      respectively. The awareness/correct rates of knowledge, attitude and practice
      reduced in turns significantly (chi2 =1 282.96, P < 0.01). The knowledge
      awareness rate of fishermen and boatmen was 90.98%, but their attitude correct
      rate was only 53.81% ( chi2 =120.52, P < 0.01). The unconditional logistic
      regression analysis showed that with the education level increasing, their
      practice correct rate rose, and the participants with the college degree or above
      had a higher correct rate compared to illeterate ones (OR = 6.411, 95% CI: 4.896
      8.395). The practice correct rate of the fisher-men and boatmen was only 5.1% of
      the rate of the farmers (OR = 0.051, 95% CI: 0.029-0.091). CONCLUSIONS: The total
      awareness rate of basic knowledge of schistosomiasis prevention and control in
      the residents of Jiangsu Province has reached the requirements in the "National
      Schistosomiasis Control Long-term Planning Outline (2004-2015)", but the correct
      rate of behaviors is low. The education level, occupation and residential areas
      affect the health behaviors of schistosomiasis prevention and control. Therefore,
      it is necessary to carry out targeted health promotion activities to promote the
      formation of healthy lifestyle and behaviors.

PMID- 29469352
TI  - [Survey of epidemic status of paragonimiasis in western mountainous areas in
      Hubei Province].
AB  - OBJECTIVE: To understand the current status of paragonimiasis epidemic in western
      mountain areas in Hubei Province. METHODS: Four counties (cities) of Western
      Hubei Province (Xingshan, Enshi, Yunxi, Baokang) were selected as the
      investigation sites for active surveillance. Crabs were captured and the
      metacercariae of Paragonimus were detected. Meanwhile, the blood samples were
      collected from the residents in the surveillance sites and the unique IgG and IgM
      antibodies against Paragonimus in the sera were detected by ELISA. In addition, a
      questionnaire survey about knowledge and behavior of prevention and control of
      paragonimiasis was taken among the residents. RESULTS: A total of 1 143 residents
      were investigated in the active surveillance, the total positive rate of the
      serology test was 1.84% (21/1 143), while the rates of the male and the female
      were 1.78% (10/562) and 1.89% (11/581), respectively, with no statistical
      significance between them ( chi2 = 0.002, P > 0.05). The average weight of 161
      fresh-water crabs captured was 11.72 g, with the positive rate of 9.32% (15/161)
      and the infective density of 7.07 metacercariae per positive crab. The positive
      rates of the male and female crabs were 11.54% (9/78) and 7.23% (6/83),
      respectively ( chi2 = 0.884, P > 0.05), and the infective densities were 6.67 and
      7.67 metacercariae per positive crab, respectively. Totally 1 143 residents were
      investigated by questionnaires, and 0.44% of them had the behavior of eating raw
      or half-done fresh-water crab, and 0.87% of them had the behavior of drinking un
      boiled stream water. CONCLUSIONS: The transmission chain of paragonimiasis still
      exists in the nature environment of mountain area in Western Hubei Province. The
      positive rate of the second intermediate host rebounds in some investigation
      sites. Therefore, the measures of continuous surveillance and health education
      should be taken to avoid the appearance of the prevalence or outbreak.

PMID- 29469353
TI  - [Monitoring results of soil-transmitted nematodiasis in national surveillance
      site of Huaiyang County in Henan Province, 2006-2015].
AB  - OBJECTIVE: To understand the epidemic situation of soil-transmitted nematodiasis
      in the national surveillance site in Henan Province. METHODS: Over 1 000 fecal
      samples from inhabitants in Huaiyang County of Henan Province, which was a
      national surveillance site, were collected each year from 2006 to 2015, the eggs
      of soil-transmitted nematodes and other intestinal helminths were examined by
      Kato-Kats technique. The cellophane swab method was used to detect Enterobius
      vermicularis eggs in children aged 3 to 12 years. In addition, the soil samples
      were collected from vegetable fields, lavatories, courtyards and kitchens of 10
      families randomly selected in each year to examine Ascaris eggs by a modified
      saturated sodium nitrate floatation method. RESULTS: From 2006 to 2015, 10 419
      persons were investigated, and the eggs of five species of intestinal helminths,
      Ascaris lumbricoides, Trichuris trichiura, hookworm, E. vermicularis, and
      Trichostrongylus orientalis, were detected, The average infection rate of soil
      transmitted nematodes in residents in Huaiyang County was 3.69%. The intensity of
      infection was mild and a family clustering was obvious. Both the infection rates
      of E. vermicularis in children and soil-transmitted nematodes in villagers had no
      significant differences between different genders (both P>0.05). The infection
      rates of soil-transmitted nematodes, A. lumbricoides and E. vermicularis all
      reached the highest in the age group of 1-10 years. For different education back
      ground, the people with primary school education had the highest infection rate,
      and the infection rate showed a decreasing trend with the increase of the
      educational level. The infection rate of soil-transmitted nematodes in the
      national surveillance site in Henan Province showed a decreasing trend from 2006
      to 2015. Unfertilized and fertilized A. lumbricoides eggs were detected in the
      soil samples, but the positive rate was very low. CONCLUSIONS: In the recent 10
      years, the infection rate of soil-transmitted nematodes in the national
      surveillance site in Henan Province shows a decreasing trend and maintains at a
      low level. The infection shows a family clustering. The children, especially
      those aged 3-9 years are the main infected population, and E. vermicularis
      infection is the key point of prevention and control.

PMID- 29469354
TI  - [Study on natural population dynamics and spatial distribution pattern of
      Tyrophagus putrescentiae in stored flour].
AB  - OBJECTIVE: To understand the natural population dynamics and spatial distribution
      of Tyrophagus putrescentiae in storage flour, so as to provide an evidence for
      its prevention and control. METHODS: The samples from five sampling points in
      Wuhu City were collected monthly from January to December, 2013, and examined and
      counted for T. putrescentiae. The dispersion pattern target, Iwao's m*- x;
      regression analysis and Taylor's lgS2-lg x; regression analysis were used for
      analyzing the spatial distribution pattern of T. putrescentiae in the storage
      flour. RESULTS: The peaks of population dynamics of T. putrescentiae were
      discovered in July and September. The indexes of dispersion were as follows:I >
      0, CA > 0, m*/ x; > 1; and the linear regression equation of Iwao:m* = 3.740 3 +
      1.017 5 x; (r = 0.995 8) and Taylor:lgS2 = 0.500 4 + 1.134 9 lg x; (r =0.832 8)
      showed that the spatial distribution pattern of T. putrescentiae in the storage
      flour was assembled. CONCLUSIONS: The peak of population dynamics of T.
      putrescentiae in the storage flour in Wuhu City is a double peak type, and the
      spatial distribution pattern of T. putrescentiae is assembled.

PMID- 29469355
TI  - [Analysis of projects of schistosomiasis sponsored by National Science Foundation
      of China].
AB  - OBJECTIVE: To summarize the present development by analysis of projects in
      schistosomiasis funded by National Science Foundation of China (NSFC). METHODS:
      Based on the ISIS database of NFSC, the projects in the studies of
      schistosomiasis from 2005 to 2016 were analyzed. The distributions of sponsored
      numbers, amounts, types, agencies, disciplines and changes in research topics by
      means of network profiles were described. RESULTS: During the study period, 198
      projects were funded by NSFC totally with 76.05 million yuan in which the general
      and youth projects were main types. The main sponsored agencies were research
      institutes and medical colleges. The top three fields sponsored were medical
      pathogenic microbes and infection, veterinary and medical immunology.
      CONCLUSIONS: The funding on schistosomiasis researches has a downward trend, but
      studies are continuing in depth. In this situation, innovative and
      interdisciplinary researches need to be encouraged to promote the development of
      schistosomiasis.

PMID- 29469356
TI  - [Genetic variation of Thelazia callipaeda among isolates collected from patients
      in Zunyi City, Guizhou Province].
AB  - OBJECTIVE: To identify the genetic variation and possible sources of Thelazia
      callipaeda isolates collected from patients in Zunyi City, Guizhou Province.
      METHODS: Seven cases of T. callipaeda infection in Zunyi City, 2016 were
      verified, and DNA (s) were extracted from the T. callipaeda's body collected from
      the thelaziasis patients. A mitochondrial COX1 fragment was amplified and
      sequenced. The sequence alignment and phylogenetical analysis were performed to
      compare the genetic variation of the gene sequence with the homologous sequences
      downloaded from Genebank. RESULTS: COX1 genes of T. callipaeda were differed
      among the samples from the seven cases, which had low variation. CONCLUSIONS:
      Zunyi City is a new area with endemic of thelaziasis. The isolates from Zunyi
      City include either Asian origin or European origin of T. callipaeda. Moreover,
      at least four haplotypes are identified among the seven isolates.

PMID- 29469357
TI  - [Correlation between HLA-DB1 genes and susceptibility to echinococcosis in
      Tibetan population in Tibetan Plateau].
AB  - OBJECTIVE: To determine the susceptibility genes and resistance genes in HLA-DRB1
      alleles in Tibetan patients with cystic and alveolar hydatid diseases, so as to
      provide the references for the research of the genetic characteristics and
      infection mechanism of Tibetan hydatid diseases. METHODS: The case control method
      was applied. The Tibetan patients with cystic and alveolar hydatid diseases (63
      and 73 cases respectively) in Yushu and Guoluo Tibetan Autonomous Prefecture, and
      unrelated healthy people (60 cases) in this area were selected as the study
      subjects. The polymerase chain reaction-sequence based typing (PCR-SBT) technique
      was applied for genotyping of HLA-DRB1, and the comparison of the gene frequency.
      RESULTS: The frequency of HLA-DRB1*04 in the alveolar/cystic echinococcosis group
      was lower than that in the control group ( chi2 = 4.71, 4.31, both P < 0.05).
      CONCLUSIONS: HLA-DRB1*04 genotypes may be associated with the resistance of
      cystic and alveolar echinococcosis and its resistance genes.

PMID- 29469358
TI  - [Survey and analysis of epidemic status of principal human parasitosis in
      ecological region of Huaiyang hills of Henan Province in 2015].
AB  - OBJECTIVE: To understand the epidemic status of principal human parasitosis in
      the ecological region of Huaiyang hills of Henan Province. METHODS: According to
      the scheme of The 3rd National Survey of Principal Human Parasites made by
      National Institute of Parasitic Diseases, the survey was performed based on the
      ecological regions. The stratified cluster sampling was made combined with the
      economic and geographical conditions. The infections of intestinal helminths and
      protozoans in permanent residents were respectively detected by Kato-Kats
      technique and iodine solution. Trichuris trichiura infection was detected by the
      cellophane swab method in children aged 3 to 6 years. RESULTS: Totally 6 710
      residents in 26 survey spots from 9 counties were detected, in which 528 children
      aged 3 to 6 years were detected for T. trichiura infection. Eleven kinds of
      parasites were found in this survey, including 5 species of helminthes and 6
      species of protozoans. The infection rates of overall parasites, helminthes and
      protozoans were respectively 1.65%, 1.07% and 0.61%. The infection rate of T.
      trichiura in the children aged 3 to 6 years was 3.79%. Only 0.10 percent of the
      infections were co-infection, and all were infected by 2 kinds of parasites. The
      principal parasites in this district were Ascaris lumbricoides (0.31%),
      Blastocystis hominis (0.28%) and hookworm (0.27%). The T. trichiura infection
      rate among children was 3.79% by the cellophane swab method. The infections of
      protozoans were found in all age groups. In the group aged 9 years and below, the
      maximum kinds of parasites were found. CONCLUSIONS: The infection rates of
      principal human parasites in Huaiyang hilly ecological region of Henan have
      decreased sharply, but more efforts still should be paid on the prevention and
      control of parasitosis in children.

PMID- 29469359
TI  - [Gohieria fusca found in dust of air-conditioner filters].
AB  - OBJECTIVE: To investigate the pollution status of Gohieria fusca in the air
      conditioner-filters of different places in Wuhu City. METHODS: The dust samples
      were collected from the filters of air-conditioners in dining rooms, shopping
      malls, hotels and households between June and September, 2013, and G. fusca was
      detected in the dust samples. RESULTS: There were 430 dust samples collected and
      98 were G. fusca positive with the breeding rate of 22.79%. The difference of
      breeding rates of G. fusca were statistically significant among the different
      places ( chi2 =18.294, P < 0.05). Among 510.5 g dust samples in total, 783 G.
      fusca mites were detected with an average breeding density of 1.53 mite/g.
      CONCLUSIONS: G. fusca breeds in the dust of air-conditioner filters in Wuhu City
      gravely.

PMID- 29469360
TI  - [Application of electronic fence technology based on GIS in Oncomelania hupensis
      snail monitoring].
AB  - OBJECTIVE: To study the application of Geographic Information System (GIS)
      electronic fence technique in Oncomelania hupensis snail monitoring. METHODS: The
      electronic fence was set around the history and existing snail environments in
      the electronic map, the information about snail monitoring and controlling was
      linked to the electronic fence, and the snail monitoring information system was
      established on these bases. The monitoring information was input through the
      computer and smart phone. RESULTS: The electronic fence around the history and
      existing snail environments was set in the electronic map (Baidu map), and the
      snail monitoring information system and smart phone APP were established. The
      monitoring information was input and upload real-time, and the snail monitoring
      information was demonstrated in real time on Baidu map. CONCLUSIONS: By using the
      electronic fence technology based on GIS, the unique "environment electronic
      archives" for each snail monitoring environment can be established in the
      electronic map, and real-time, dynamic monitoring and visual management can be
      realized.

PMID- 29469361
TI  - [Surveillance of schistosomiasis transmission risk in Jingmen City, Hubei
      Province].
AB  - OBJECTIVE: To investigate the risk factors of schistosomiasis transmission in
      Jingmen City. METHODS: The Oncomelania hupensis snails, the wild animal feces,
      and infection source were selected as the monitoring objects to carry out the
      schistosomiasis risk monitoring. I-III levels of risk environments were treated
      with appropriate measures. RESULTS: A total of 52 environments and three water
      systems were monitored and 1 542 snails were dissected but no Schistosoma
      infected snails were found. Nine fecal samples were collected from the areas with
      snails, and no eggs of Schistosoma were found. Eighty-nine samples of
      cattle/sheep faces, and mice and dogs were collected, and three samples of cattle
      feces were found with Schistosoma eggs. Five environments were assessed as Grade
      II, and 48 environments were assessed as Grade III, and 2 environments were
      assessed as no risk of schistosomiasis transmission. CONCLUSIONS: In Jingmen
      City, the mollusciciding work from May to June could decrease the density of
      snails and the risk of schistosomiasis transmission efficiently. The schistosome
      infected cattle were the main infection source, and therefore, the cattle and
      snails should be administrated simultaneously.

PMID- 29469362
TI  - [Effect of schistosomiasis control in Yangxin County, Hubei Province, 2004-2015].
AB  - OBJECTIVE: To evaluate the effect of schistosomiasis control and prevention in
      Yangxin County from 2004 to 2015, so as to provide the evidence for improving the
      work of schistosomiasis transmission interrupted and elimination in the future.
      METHODS: According to the endemic types and endemic regularity of schistosomiasis
      in Yangxin County, the comprehensive control strategies were adopted, and the
      programs related to sanitation, water conservancy, forestry, and agriculture were
      implemented continuously. The schistosomiasis control effects in this county from
      2004 to 2015 were analyzed and compared. RESULTS: After the implementation of the
      schistosomiasis comprehensive control strategies in Yangxin County, the
      calculated number of patients reduced from 22 240 in 2004 to 1 471 in 2015, the
      infection rate of residents reduced from 8.57% in 2004 to 0.16% in 2015, the
      number of patients with acute schistosome infection reduced from 64 in 2004 to 0,
      and no cases of acute schistosomiasis found since 2009. The infection rate of
      cattle decreased from 8.87% in 2004 to 0. The area with Oncomelania hupensis
      snails and the area of susceptible zone reduced from 3 446.21 hm2 and 1 111.59
      hm2 in 2004 to 2 285.75 hm2 and 41.28 hm2 in 2015 respectively, and the
      schistosome-infection rate of snails reduced from 0.76% in 2004 to 0.
      CONCLUSIONS: Since the comprehensive control strategy implemented from 2004, the
      endemic situation of schistosomiasis in Yangxin County has decreased
      significantly. However, the harness force of the Fu River as well as the control
      of infection source of livestock still should be strengthened to consolidate the
      control achievement.

PMID- 29469364
TI  - [Epidemiological characteristics of malaria in Leshan City, 1950-2015].
AB  - OBJECTIVE: To analyze the epidemiological characteristics of malaria in Leshan
      City, so as to provide the evidence for formulating the strategy and measures for
      consolidating the achievements of malaria elimination. METHODS: The data of
      epidemiological characteristics of malaria in Leshan City from 1950 to 2015 were
      collected and analyzed with the descriptive epidemiology method. RESULTS: There
      were four larger scale epidemics of malaria in Leshan City from 1950 to 2015. The
      order of malaria in infectious diseases dropped from the first to the twentieth.
      The peak season for malaria epidemics ceased. The Plasmodium species, patient
      age, occupation and sex distribution of malaria were different in the different
      periods. In November 2016, the whole city achieved the national standard for
      malaria elimination. CONCLUSIONS: After years of prevention and control, the
      epidemiological characteristics of malaria have changed significantly in Leshan
      City, and the effect of anti-malarial measures is significant. In the future, we
      should strengthen the monitoring, and prevention and control of imported malaria.

PMID- 29469363
TI  - [Malaria focus investigation and disposal in Tengchong City between 2015 and
      2016].
AB  - OBJECTIVE: To analyze the results of malaria focus investigation and disposal in
      Tengchong City, Yunnan Province between 2015 and 2016, so as to provide evidences
      for interrupting potential malaria transmission. METHODS: The malaria foci were
      investigated and disposed according to the malaria cases reported from "China
      Information System for Disease Control and Prevention" in Tengchong City between
      2015 and 2016. The mosquitoes were captured by mosquito-lured lamp overnight to
      investigate the malaria vector in local. The peripheral blood samples were
      collected from the local residents with a febrile history in the foci within two
      weeks and the accompanists of the cases, and then the rapid malaria diagnosis
      tests were used to screen the malaria carriers. RESULTS: Totally 145 imported
      malaria cases were reported in Tengchong City between 2015 and 2016, and the
      focus investigation and disposal rate within 7 d was 100% (145/145). A total of
      16 186 mosquitoes of 12 species of Anopheles were captured, among which An.
      sinensis was the predominant, accounting for 64.31% (10 410/16 186), followed by
      An. kunmingensis and An. minimus, with the constituent ratios of 14.15% (2 291/16
      186) and 11.66% (1 887/16 186), respectively. One person (1.96%, 1/51) in the 51
      accompanists of the cases was positive in the malaria rapid diagnosis test.
      CONCLUSIONS: The malaria transmission vectors such as An. sinensis, An.
      kunmingensis, An. minimus etc. are still distributed in Tengchong City, and An.
      sinensis is the predominant species. Therefore, the relevant authorities should
      continue to strengthen the focus investigation and disposal to interrupt the
      potential introduced malaria transmission by imported cases in the future.

PMID- 29469365
TI  - [Epidemic characteristics of imported falciparum malaria in Huai'an City].
AB  - OBJECTIVE: To understand the situation and epidemic characteristics of imported
      falciparum malaria in Huai'an City from 2010 to 2016, so as to provide the
      evidence for formulating the prevention and control strategies of imported
      falciparum malaria in the city. METHODS: The epidemic data of imported falciparum
      malaria in Huai'an City from 2010 to 2016 were analyzed by using the descriptive
      epidemiological method. RESULTS: A total of 308 malaria cases were reported in
      Huai'an City from 2010 to 2016 with the average annual incidence of 0.88/105. A
      total of 240 imported falciparum malaria cases were reported, of which 18 cases
      (7.50%) developed into severe illness, and 2 severe patients died. The cases were
      reported in every county (district), and the incidence rates of Qingpu District
      and Huai'an District were higher than the city average level. The cases occurred
      every month, so there was no significant seasonal variation in the reporting time
      of the cases. Most of the patients were young men and aged 30-49 years. The
      occupational distribution revealed that the patients were mainly farmers, workers
      and migrant workers. The main source of infection was from African countries. The
      median interval from symptom appearing to definite diagnosis was 1 day, and the
      longest interval was 236 days. Twenty-nine cases were diagnosed within 24 hours,
      accounting for 12.08%. CONCLUSIONS: The epidemic situation of imported falciparum
      malaria in Huai'an City is grim. In order to consolidate the achievements of
      malaria eradication, it is necessary to further improve the multi-sectoral
      cooperation mechanism, strengthen the management of floating population and take
      effective measures to reduce the risk of imported falciparum malaria.

PMID- 29469366
TI  - [Hypopus of Acarus siro found in stored wheat].
AB  - OBJECTIVE: To observe the morphological characteristics of hypopus of Acarus siro
      in the stored wheat in Linquan County, Anhui Province. METHODS: The wheat samples
      were collected from the wheat which had been stored for more than six months. The
      hypopodes of A. siro were isolated from the stored wheat, and were made into the
      glass specimens, and then were identified under an optical microscope. RESULTS:
      The structural features of the hypopus were found under the microscope, such as
      the setae of tibia and setae of genu, and the foot claws were well-developed, and
      the genital seta bases and the pair of sucker were almost at the same baseline.
      CONCLUSIONS: The hypopodes of A. siro are found in the stored wheat, and
      therefore, the effective measures should be taken to control the hazard to the
      stored grain.

PMID- 29469367
TI  - [Analysis of human intestinal nematode infections in Nanjing City from 2006 to
      2015].
AB  - OBJECTIVE: To analyze the epidemiological situation of human intestinal nematode
      infections in Nanjing City from 2006 to 2015, so as to provide the reference for
      formulating prevention and control measures. METHODS: The surveillance data of
      human intestinal nematode infections in Nanjing City from 2006 to 2015 were
      collected and analyzed statistically. RESULTS: From 2006 to 2015, 98 804 person
      times of residents were surveyed in Nanjing City, and 465 person-times of
      residents were detected with intestinal nematode infections. The highest
      infection rate was in 2006 (1.97%), and the lowest in 2013 and 2015 (both 0.05%).
      Moreover, the positive rate of human intestinal nematode infections showed a
      significantly declining trend in total ( chi2 = 552.19, P < 0.001). Meanwhile,
      the numbers of Ascaris lumbricoides, hookworm and Trichuris trichura cases were
      329, 98 and 25 respectively, and the infection rates were 0.33%, 0.10% and 0.03%
      respectively. Among them, 443 cases had mild infection intensity (98.66%). There
      were 462 cases of single-infection (99.35%), and 3 of co-infection of two
      parasites (0.65%). From 2006 to 2015, 92 539 person-times of children under 12
      years old were surveyed for Enterobius vermicularis infection and 352 cases were
      detected with E. vermicularis infection. Moreover, the positive rate showed a
      significantly decreasing trend in total (chi2 = 147.94, P <0.001). CONCLUSIONS:
      The control effect of human intestinal nematode infections in Nanjing City is
      remarkable. However, the surveillance and health education in key groups still
      should be strengthened, and the prevention and control programs should be
      adjusted promptly to further consolidating the effectiveness of intestinal
      nematode disease prevention and control.

PMID- 29469368
TI  - [Survey of human major parasitic diseases in Shixing County from 2002 to 2016].
AB  - OBJECTIVE: To analyze the results of 3 investigations (2002-2004, 2008-2009, and
      2016) of major parasitic diseases in Shixing County, so as to provide the
      evidence for formulating further control strategies. METHODS: With the stratified
      cluster sampling method, 5 administrative villages were investigated. A total of
      200 residents aged above 3 years were sampled in each village to investigate the
      eggs of soil-transmitted nematodes with Kato-Katz technique, and the swab method
      was applied for detecting the eggs of Enterobius vermicularis in children aged 3
      9 years. chi2 test was used for statistical analysis. RESULTS: Totally 3 857
      individuals were surveyed for intestinal parasites, and 5 species of parasites
      were found and the total infection rates were 28.37%, 4.32% and 0.50% in the 3
      investigations respectively, and there were statistically significant differences
      between any two investigations ( chi2 = 287.64, 327.60 and 31.89 respectively,
      and all P< 0.01). The infection rates of Ascaris lumbricoides, hookworm,
      Trichuris trichiura and Clonorchis sinensis significantly decreased in the third
      investigation compared with those in the first investigation ( chi2 = 424.55,
      55.45, 43.40 and 26.12 respectively, all P< 0.01). However, there was no
      significant difference between the E. vermicularis infection rates of the first
      investigation and the third investigation ( chi2 =0.16, P >0.05). CONCLUSIONS:
      Compared with the status in the first investigation, the infection rates of A.
      lumbricoides, hookworm, T. trichiura and C. sinensis are significantly decreased
      by 90% or more in the third investigation. However, the children's infection rate
      of E. vermicularis is still very high. Therefore, we should focus on the
      comprehensive control measures of E. vermicularis infection while formulating
      further control strategies of parasitic diseases.

PMID- 29469369
TI  - [Analysis of effect of prevention and control technique training of human
      important parasitic diseases in Jiangsu Province in 2017].
AB  - OBJECTIVE: To evaluate the effect of the prevention and control technique
      training of human important parasitic diseases for basic professional and
      technical personnel in Jiangsu Province in 2017. METHODS: A workshop including
      theory courses and practical operations was carried out for the basic
      professional and technical personnel. At the end of the workshop, the effects
      were evaluated through the theoretical and microscopic examinations. RESULTS:
      There were 132 trainees from 13 cities, and all of them took part in the final
      examinations. The average score of total was 118.36. There were significant
      differences among different regions ( chi2 = 13.38, P < 0.01). The pass rate of
      the theory test was 92.4% with the average score of 79.05. There were significant
      differences of theory scores among different regions ( chi2 =14.51, P < 0.01).
      The theory score of Northern Jiangsu Province was significantly higher than the
      scores of Southern and Central Jiangsu Province (P < 0.001, P = 0.009). The pass
      rate of microscopic examinations was 89.4% with the average score of 39.32. There
      was no significant difference of micro-scopic examination scores among different
      regions (F = 2.37, P = 0.09). Among the total 7 species, the detection rate of
      Paragonimus westermani was the highest (75%) and the rates of Schistosoma
      japonicum and Fasciolopsis buski were only 51.5% and 54.5% respectively. The
      detection rates of eggs of Trichuris trichiura, unfertilized Ascaris
      lumbricoides, Clonorchis sinensis and Taenia solium were 71.2%, 65.9%, 72.7% and
      72.0% respectively. CONCLUSIONS: The training course has promoted the capability
      of prevention and control of parasitic diseases for basic technical personnel.
      Also it provides the technical supports for parasitic disease monitoring, control
      and risk assessment in the next step.

PMID- 29469370
TI  - [Ixodes ovatus found in Huainan area in Anhui Province].
AB  - OBJECTIVE: To study the morphological characteristics of Ixodes ovatus in order
      to provide the evidence for future research. METHODS: A group of goats were
      randomly selected and checked one by one, and the ticks were collected. RESULTS:
      A hard tick was found on the surface of a goat, and it was identified as Ixodes
      ovatus. CONCLUSIONS: Ixodes ovatus has been found in Huainan area in Anhui
      Province, confirming that Huainan area is a new breeding place of Ixodes ovatus.
      This finding may contribute to the epidemiological research of tick-borne
      diseases.

PMID- 29469371
TI  - [Therapeutic effect of BILT combined with praziquantel in treatment of chronic
      schistosomiasis].
AB  - OBJECTIVE: To investigate the clinical therapeutic effect of biological
      information infrared liver therapeutic apparatus (BILT) combined with
      praziquantel in the treatment of patients with chronic schistosomiasis. METHODS:
      A case-control study was conducted. A total of 142 chronic schistosomiasis
      patients were divided into an experimental group (BILT combined with
      praziquantel) with 64 cases and a control group (routine treatment with
      praziquantel alone) with 78 cases on the basis of the age, gender, disease
      duration and liver function as paired condition. Fatigue, diarrhea, abdominal
      distension, liver function, hyaluronic acid (HA) and laminin (LN) were as
      observation indexes and the observation results were compared between two groups.
      RESULTS: Before the treatment, there were no significant differences between the
      two groups in the indexes above-mentioned (P > 0.05). After the treatment, the
      incidence rates of fatigue, diarrhea, abdominal distension, abnormal liver
      function, and the levels of HA and LN in the experimental group were
      significantly lower than those in the control group (P < 0.01). CONCLUSIONS: BILT
      combined with praziquantel can significantly alleviate the short-term clinical
      symptoms, restore liver function and also alleviate hepatic fibrosis of the
      patients with chronic schistosomiasis.

PMID- 29469372
TI  - [A review of spatial epidemiology with malaria surveillance and control in
      China].
AB  - The monitoring and control of malaria depends largely on the spatial analysis
      technology and mathematical models. Visualization of malaria situation is the
      most popular way to present how malaria transmits. In this paper, the malaria
      epidemic situation and the application of spatial epidemiology of malaria in
      China are summarized, so as to provide the systematic epidemiological information
      for malaria elimination in China.

PMID- 29469373
TI  - [Imaging findings and progress of schistosomal hepatopathy].
AB  - Schistosomal hepatopathy is widespread in China, and there were more than 30 000
      schistosomiasis patients with serious liver fibrosis in 2015. This article
      reviews the pathological manifestations, clinical presentations, imaging findings
      as well as imaging diagnosis value of schistosomal hepatopathy, and mainly
      reviews the progress of the typical imaging manifestations of schistosomal
      hepatopathy and new imaging methods for evaluating the liver fibrosis.

PMID- 29469374
TI  - [Epidemic situation and control strategy of major food - borne parasitic diseases
      in Guangxi Zhuang Autonomous Region].
AB  - Food-borne parasitic diseases have become a public health problem for social
      economy and health care. In this paper, the epidemic situation of major food
      borne parasitic diseases in Guangxi Zhuang Autonomous Region, such as
      toxoplasmosis and clonorchiasis, are reviewed, and the countermeasures of
      prevention and control are put forward.

PMID- 29469375
TI  - [One case report of ectopic schistosomiasis in fallopian tube in Jingmen City].
AB  - One cases of ectopic schistosomiasis in fallopian tube was found by the
      histopathological examination in Jingmen City. After surgery and anthelmintic
      treatment with praziquantel, the curative effect was satisfactory. This case
      suggests that in schistosomiasis endemic area, the imaging technology and tissue
      pathological examination should be used sufficiently for the differential
      diagnosis of ectopic schistosomiasis, so as to reduce misdiagnosis.

PMID- 29469376
TI  - [Investigation of a case of foreign imported falciparum malaria in Xilin County,
      Baise City].
AB  - OBJECTIVE: To investigate the epidemiology, diagnosis and treatment of an
      imported falciparum malaria patient in Xilin County, Baise City, so as to provide
      the reference for improving the diagnosis and treatment of falciparum malaria
      patients in the future. METHODS: The epidemiological and clinical data were
      collected and analyzed. RESULTS: The patient had lived in Africa where the
      malaria was epidemic. The disease attacked him after his coming back home from
      abroad. The blood test for Plasmodium falciparum was positive. In Xilin County,
      no local Plasmodium infection was found from 2004 to 2016, and therefore, we
      concluded that this case was overseas imported. CONCLUSIONS: The monitoring of
      overseas returnees in Xilin County should be strengthened to timely diagnose and
      treat the imported cases of malaria.

PMID- 29469377
TI  - [Playing the guiding roles of national criteria and precisely eliminating
      schistosomiasis in P. R. China].
AB  - Schistosomiasis Control and Elimination (GB 15976-2015) and Diagnostic Criteria
      for Schistosomiasis (WS 261-2006) are the only two national health criteria
      related to schistosomiasis control program implemented in P. R. China. The roles
      of criteria to guide and accelerate the transition from schistosomiasis control
      to elimination are concluded, based on this systematic review how the criteria
      led the implementation of the medium- and long-term national plan and provided
      the guidance when drafting the thirteen-five years national plan for
      schistosomiasis, and the suggestion to draft more criteria related to
      schistosomiasis elimination program and strengthening the implementation of
      current criteria, so as to precisely guide the schistosomiasis elimination
      program in P. R. China.

PMID- 29469378
TI  - [Dynamic simulation analysis of effects of project of ditching for drain on
      Oncomelania hupensis snail control and flood prevention security in Dongting Lake
      region].
AB  - OBJECTIVE: To evaluate the effects of the project of ditching for drain on
      Oncomelania hupensis snail control and flood prevention security and explore the
      optimal engineering design plan in Dongting Lake region. METHODS: A retrospective
      study was performed on the previous studies about the project of ditching for
      drain. The reference values of project indices were determined. The outside levee
      of Nanhu New Distinct of Yueyang City in Dongting Lake region was selected as the
      study area, and the cross section of marshland perpendicular to the center line
      of the levee was extracted to research. According to the situations of various
      water levels, a dynamic simulation was performed on the effect and security of
      the project of ditching for drain through the software FLAC3D. RESULTS: The
      retrospective study showed that the project would be effective when the
      relatively subsoil water level decreased by 0.35 m, and the soil water content
      decreased correspondingly. The dynamic simulation by FLAC3D showed that the
      minimum safe distances between transverse ditch 1, vertical ditch and levee toe
      should be 25 m and 13 m respectively. The digging depth of transverse ditch and
      vertical ditch should be 1.2 m and 1.0 m respectively. If the width of marshland
      in drought period was less than 500 m, one transverse ditch was efficient.
      Otherwise, more transverse ditches should be set with the intervals of 300 m.
      CONCLUSIONS: The project of ditching for drain is an effective ecological snail
      elimination method. Optimizing the digging depth of ditches and distances between
      transverse ditches, vertical ditch and levee toe will ensure the effects and
      security of the project.

PMID- 29469379
TI  - [Maximum entropy model versus remote sensing-based methods for extracting
      Oncomelania hupensis snail habitats].
AB  - OBJECTIVE: To explore the technique of maximum entropy model for extracting
      Oncomelania hupensis snail habitats in Poyang Lake zone. METHODS: The information
      of snail habitats and related environment factors collected in Poyang Lake zone
      were integrated to set up the maximum entropy based species model and generate
      snail habitats distribution map. Two Landsat 7 ETM+ remote sensing images of both
      wet and drought seasons in Poyang Lake zone were obtained, where the two indices
      of modified normalized difference water index (MNDWI) and normalized difference
      vegetation index (NDVI) were applied to extract snail habitats. The ROC curve,
      sensitivities and specificities were applied to assess their results.
      Furthermore, the importance of the variables for snail habitats was analyzed by
      using Jackknife approach. RESULTS: The evaluation results showed that the area
      under receiver operating characteristic curve (AUC) of testing data by the remote
      sensing-based method was only 0.56, and the sensitivity and specificity were 0.23
      and 0.89 respectively. Nevertheless, those indices above-mentioned of maximum
      entropy model were 0.876, 0.89 and 0.74 respectively. The main concentration of
      snail habitats in Poyang Lake zone covered the northeast part of Yongxiu County,
      northwest of Yugan County, southwest of Poyang County and middle of Xinjian
      County, and the elevation was the most important environment variable affecting
      the distribution of snails, and the next was land surface temperature (LST).
      CONCLUSIONS: The maximum entropy model is more reliable and accurate than the
      remote sensing-based method for the sake of extracting snail habitats, which has
      certain guiding significance for the relevant departments to carry out measures
      to prevent and control high-risk snail habitats.

PMID- 29469380
TI  - [Emergency response and effect evaluation on schistosomiasis control in rescue of
      shipwreck event in Yangtze River].
AB  - OBJECTIVE: To evaluate the effect of schistosomiasis control in"Oriental Star
      shipwreck event"in Jianli County, Hubei Province, so as to provide experiences
      for schistosomiasis prevention and control in rescue of emergency in the future.
      METHODS: According to the data of historical schistosomiasis prevalence and the
      results of the field survey in the townships in the upstream and downstream of
      the rescue spots, the emergency handling measures of schistosomiasis control were
      evaluated. Meanwhile, the Oncomelania hupensis snail situation, priority crowd
      chemotherapy, key aquatic monitoring, and illness monitoring of people and
      livestock were investigated to evaluate the schistosomiasis control effect after
      the events comprehensively. RESULTS: There were no schistosome-infected snails
      found in the place of shipwreck and the rescue spots. The average density of O.
      hupensis snails in 5 townships of Jianli County was 0.064 snails/0.1 m2, and
      there were no infected snails found. The positive rate of 2 090 migrants in the
      schistosomiasis serologic tests was 0.29% and there were no positive ones found
      in the fecal examination. There were no acute schistosomiasis cases found by the
      sentinel surveillance fever clinics, and also no positive cattle were found. The
      results of sentinel mice monitoring in the place of shipwreck and 4 villages in
      the upstream and downstream showed no infected mice were found. CONCLUSIONS: The
      schistosomiasis control measures taken after the shipwreck is effective, which
      achieves the goal of no schistosomiasis transmission after emergency.

PMID- 29469381
TI  - [Geographical features of malaria in Yunnan Province].
AB  - OBJECTIVE: To understand the geographical features of malaria in Yunnan Province,
      so as to provide the reference for malaria elimination. METHODS: The data of
      malaria in Yunnan Province from 2012 to 2015 were collected and analyzed.
      RESULTS: Totally 2 586 malaria cases were reported in Yunnan Province from 2012
      to 2015, in which 274 (10.60%) were local cases and 2 311 (89.37%) were abroad
      imported, and one (0.03%) was domestic imported. The imported malaria cases and
      local cases were analyzed according to the sources and locations respectively,
      and the arithmetic means of the numbers of imported and local cases were 96.29
      and 10.96 respectively, the standard deviations of the numbers of imported and
      local cases were 421.18 and 19.12 respectively, and the difference of the means
      was not significant (Z = - 0.326, P > 0.10). Both the imported and local malaria
      cases could be clustered into five sections by the number of 5. The Herfendal
      Hirshman indexes of the imported and local malaria cases were 8 121 and 1 598
      respectively. CONCLUSIONS: There is no significant difference of the distribution
      between the imported and local malaria cases, and they should be attaching equal
      importance. The non-uniform degree of imported cases is higher than that of the
      local cases, while both of them could be divided into five major clusters in the
      prevention and control work.

PMID- 29469382
TI  - [Establishment of malaria early warning system in Jiangsu Province VIII Malaria
      vector monitoring in Jiangsu Province].
AB  - OBJECTIVE: To understand the population, density, seasonal fluctuation and
      nocturnal pattern of malaria vectors in Jiangsu Province, thus to provide
      evidences for malaria elimination in this province. METHODS: Seven counties
      (cities, districts) were selected as the monitoring sites for malaria vectors in
      Jiangsu Province from 2013 to 2015. The mosquitoes were captured by human bait
      trapping in bed nets and mosquito-lured lamp overnight, and the seasonal
      fluctuation and nocturnal pattern of malaria vectors were observed. RESULTS: A
      total of 11 041 Anopheles sinensis mosquitoes were captured by the mosquito-lured
      lamps in 7 counties of Jiangsu Province from 2013 to 2015, and no An.
      anthropophagous was found. Among all the 7 monitoring sites, the number of An.
      sinensis captured in Sihong County was the most (6 742 mosquitoes), while that in
      Xuyu County was the least (34 mosquitoes). During this period, the density peaks
      of An. sinensis were the first half of July, the first half of August and the
      second half of July. A total of 2 421 An. sinensis were collected in 7 monitoring
      sites from 2013 to 2015 by human bait trapping in bed nets overnight. Among all
      the 7 monitoring sites, the captured number of An. sinensis in Sihong County was
      the most (1 085 mosquitoes), while that in Ganyu County was the least (13
      mosquitoes). The nocturnal peak of An. sinensis was from 19:00 to 20:00 and 525
      An. sinensis mosquitoes were captured during this period of time, which accounted
      for 21.68% of the total. Hereafter, the captured number of An. sinensis reduced
      over time. CONCLUSIONS: The density of An. sinensis mosquitoes is still high in
      individual areas in Jiangsu Province, so the epidemic and vector monitoring still
      should be strengthened to prevent the local transmission of imported malaria.

PMID- 29469383
TI  - [Malaria epidemiological situation in Wuzhou City, Guangxi Zhuang Autonomous
      Region from 1950 to 2015].
AB  - OBJECTIVE: To review and investigate the malaria control history of Wuzhou City,
      Guangxi Zhuang Autonomous Region from 1950 to 2015, so as to provide the evidence
      for future malaria control and surveillance. METHODS: The data of malaria control
      in Wuzhou City from 1950 to 2015 were collected and analyzed. RESULTS: In 1950
      decade, the malaria incidence in Wuzhou City was 1 435.55/100 000, higher than
      the average level in Guangxi, and the mortality of malaria was 0.95/100 000. The
      malaria incidence of local residents was reduced to 3.61/100 000 in 1979 and no
      local malaria case was found since. The imported malaria cases were found in
      Wuzhou City since 1980, and were more than local cases since 1981. In recent five
      years, 87.50% (7/8) of imported malaria cases were from south-east Asia.
      CONCLUSIONS: Wuzhou City has reached the national criterion of malaria
      elimination, but the imported malaria is the recent threat. The surveillance and
      control work of malaria should be strengthened.

PMID- 29469384
TI  - [Allele genetypes and homology analysis of MSP-1 and CSP gene of Plasmodium vivax
      in Shandong Province].
AB  - OBJECTIVE: To analyze the genotypes and homology of MSP-1 and CSP gene of
      Plasmodium vivax in Shandong Province, so as to provide the evidence for case
      traceability. METHODS: A total of 12 blood samples were collected from P. vivax
      infected cases in Shandong Province in 2011. Parasite genomic DNA was extracted.
      Primers were designed according to MSP-1 and CSP gene sequences of P. vivax. Then
      Nested PCR, enzyme digestion, sequencing and sequence alignment, and homologous
      analysis were performed. RESULTS: The MSP-1 gene of all the 12 samples from P.
      vivax-infected cases were detected with a 470 bp PCR amplification band, and 350
      bp and 120 bp enzyme digestion fragments, which were identified as type Sal-1. An
      analysis of phylogenetic tree of MSP-1 gene showed that the sequences of 9
      indigenous case samples in Shandong Province were located in the same branch, one
      case sample infected from India was located in the same branch with India
      strains. All the 12 P. vivax-infected samples covered GDRA (D/A) GQPA sequences
      in CSP gene, which were identified as type PV-I. Of the CSP gene among 12 P.
      vivax-infected samples, 10 samples of indigenous case in Shandong Province and
      one sample of the case infected in Guangdong Province were detected with both 560
      840 bp and 150-230 bp PCR amplification bands, which were identified as temperate
      zone family strain of type PV-I. However, one sample from the case infected in
      India was detected only with a 560-840 bp band, which was identified as tropical
      zone family strain of PV-I. An analysis of phylogenetic tree of CSP gene showed
      that the sequences of 10 samples from the indigenous cases in Shandong Province
      and one sample from the case infected in Guangdong Province were located in the
      same branch, one sample from the case infected in India was located in the same
      branch with India and Indonesia strains. CONCLUSIONS: Of all the indigenous
      isolates in Shandong Province, MSP-1 gene is genotyped type Sal-1, CSP gene is
      genotyped temperate zone family strain of type PV-I, with a high homology found
      among the indigenous isolates.

PMID- 29469385
TI  - [Analysis of infective status of Clonorchis sinensis in Jiangxi Province].
AB  - OBJECTIVE: To understand the current prevalence of clonorchiasis in Jiangxi
      Province. METHODS: A survey was performed according to the scheme of the 3rd
      Principal Human Parasites of Jiangxi Province. Based on the ecological regions, a
      stratified cluster sampling method was applied by the economic and geographic
      situation. In rural areas, the investigation of C. sinensis was carried out
      together with the soil-transmitted helminths investigation, and in the urban
      areas, the random cluster sampling method was applied for the C. sinensis
      investigation. There were 92 survey sites from 32 counties. The eggs of C.
      sinensis in stool were examined by Kato-Katz technique, and health knowledge was
      also investigated by questionnaires in some people at the same time. RESULTS: A
      total of 23 606 sample residents were investigated, and 138 were found infected
      with C. sinensis, with the infection rate of 0.58%. Light infection was found in
      most of them. Totally 124 C. sinensis infected persons focused in Xinfeng County,
      and only a few of infected people scattered in the other counties. In Xinfeng
      County, 851 residents were investigated. Among them, the infected people were
      found in all the age groups except the 0- year age group. The highest infection
      rate appeared in the 70- years group (24.00%). The male infection rate was
      20.29%, which was higher than that of the female (6.25%), showing a statistically
      significant difference (P<0.01). The infection rate was highest in the population
      who received high school or technical secondary school education (31.48%). For
      the occupation distribution, the infection rate was highest in public officers
      (39.39%). The questionnaire survey showed that the infection rate in the
      populations in Xinfeng County who had the history of eating raw fish or raw
      shrimp was 33.15%. CONCLUSIONS: The distribution of C. sinensis infection
      presents a regional aggregation in Xinfeng County, but in other areas, the
      distribution is sporadic. It is necessary to continue to carry out the parasitic
      disease screening, and in Xinfeng County, it is necessary to strengthen the
      comprehensive prevention and control intervention.

PMID- 29469386
TI  - [Effect of exogenous nitric oxide on antioxidants from mice infected with
      Trichinella spiralis].
AB  - OBJECTIVE: To study the effect of exogenous nitric oxide donor sodium
      nitroprusside (SNP) on antioxidant enzymes activities and lipid peroxidation of
      mice infected with Trichinella spiralis. METHODS: BALB/c mice were infected with
      T. spiralis separated by the digestion method. Forty-two days post-infection, the
      peripheral blood and hepatic tissue from the infected or normal mice were
      collected. Then 4 groups were set:liver homogenate from infected mice + SNP
      (Group A), liver homogenate from normal mice + SNP (Group B), peripheral blood
      from infected mice + SNP (Group C), and peripheral blood from normal mice + SNP
      (Group D). The final concentrations of SNP in each group were set as 0 (blank
      control), 2, 5, 10 MUmol/L and 30 MUmol/L, respectively. After reacting with SNP
      at 37 C for 30 min, the superoxide dismutase (SOD), glutathione peroxidase (GSH
      Px), catalase (CAT) activities, and malondialdehyde (MDA) concentration were
      examined and compared. RESULTS: The levels of SOD, CAT, GSH-Px and MDA
      concentration in the liver and the blood from the mice infected with T. spiralis
      were significantly higher than those of the normal ones (all P < 0.05). When
      reacted with 10 MUmol/L and 30 MUmol/L SNP, the SOD, GSH-Px, and CAT activities
      in Group A and B decreased significantly (all P < 0.05), while the liver MDA
      concentration reacted with 2-30 MUmol/L SNP increased obviously (all P < 0.05).
      As reacted with 30 MUmol/L SNP, the activities of blood SOD, GSH-Px, and CAT in
      Group C and D decreased, while the MDA concentration in blood still increased
      (all P < 0.01). When the SNP concentration was in the range of 2-30 MUmol/L,
      there were a negative correlation between the SNP concentrations and SOD, GSH-Px,
      and CAT activities, as well as a positive correlation with the MDA concentration
      in the liver and blood from the mice infected with T. spiralis (all P < 0.05).
      CONCLUSIONS: T. spiralis infection could cause oxidative damage to mice, and
      increase SOD, GSH-Px, and CAT activities. Nitric oxide released from SNP can
      decrease antioxidase activities, and inhibit the antioxidant capacity of mice
      infected with T. spiralis.

PMID- 29469387
TI  - [Epidemic status of alveolar echinococcosis in Tibetan children in south Qinghai
      Province].
AB  - OBJECTIVE: To understand the epidemic status of alveolar echinococcosis in
      Tibetan children in south Qinghai Province. METHODS: The imageology and serology
      methods were applied to investigate the epidemic status of alveolar
      echinococcosis of elementary school students in Yushu and Guoluo prefectures.
      RESULTS: Totally 19 629 children were investigated by the portable B ultrasound
      and 221 children were diagnosed as alveolar echinococcosis with the morbidity of
      1.13%. Totally 9 888 were investigated by the indirect ELISA, and the positive
      rate of serum tests was 12.59% (190/9 888). The total morbidity of alveolar
      echinococcosis of children in Yushu Prefecture was 0.42% (31/7 454) and it was
      1.57% (190/12 175) in Guoluo Prefecture and there was a significant difference
      between them (chi2 = 53.42, P<0.005). The sero-positive rates of children in
      Yushu and Guoluo were 4.26% (302/7 081) and 18.56% (1 835/9 888), respectively
      (chi2 = 765.77, P<0.005). The counties with the highest prevalence of alveolar
      echinococcosis in children were Dari County (4.31%, 106/2 461) and Banma County
      (1.92%, 26/1 351) of Guoluo Prefecture, and Chengduo County (1.11%, 18/1 612) of
      Yushu Prefecture. The total morbidity rates of alveolar echinococcosis of male
      and female children were 0.91% (91/9 954) and 1.34% (130/12 175) respectively
      (chi2 = 7.35, P<0.005). The total sero-positive rates of alveolar echinococcosis
      of male and female children were 12.10% (1 037/8 568) and 13.09% (1 100/8 406)
      respectively (chi2 = 3.63, P>0.05). The total morbidity of alveolar
      echinococcosis of children in different age groups was from 1.00% to 1.13%, and
      there was no significant difference among the age groups (chi2 = 2.73, P>0.05).
      The P1a type, P1b type and P2 type accounted for 67.76% (145/214), 10.75%
      (23/214) and 16.36% (35/ 214) respectively among the alveolar echinococcosis
      patients. The diameters of nidus of 87.38% (187/214) patients were less than 5
      cm, and 2.80% (6/214) were more than 10 cm. CONCLUSIONS: The epidemic status of
      alveolar echinococcosis of Tibetan children in south Qinghai Province is serious,
      but most of the patients were at early stage of the disease. The screening work
      of alveolar echinococcosis should be strengthened in Tibetan children, so as to
      perform the early diagnosis and treatment.

PMID- 29469388
TI  - [A specific immune therapeutic effect of Der p2 T cell epitope vaccine on asthma
      mice].
AB  - OBJECTIVE: To investigate the specific immune therapeutic effect of the T cell
      fusion peptide vaccine from group II allergens from Dermatophagoides
      pteronyssinus (Der p2). METHODS: Thirty mice were randomly divided into three
      groups, namely a negative control group (a PBS group), positive control group (an
      asthma group) and protein Der p2 T cell fusion epitope for specific immunotherapy
      (SIT) group (a Der p2 T group). The extract of house dust mites (HDM) was used to
      establish the asthmatic models in BALB/c mice, and the PBS group was always used
      with PBS buffer. Thirty minutes before spray inhalation from 25 to 27 days, the
      mice of the Der p2 T group were respectively injected subcutaneously with the
      therapeutic proteins for SIT, then the serum and bronchoalveolar lavage fluid
      (BALF) were collected. ELISA was used to assay the levels of IFN-gamma, IL-4, and
      IL-13 in BALF, as well as serum levels of specific IgE and IgG2a. The lung tissue
      sections were stained with haematoxylin and eosin (H&E) for pathological
      examinations. RESULTS: The ELISA detection revealed that the number of eosinophil
      in BALF of the asthmatic mice was (5.57 +/- 0.64)*105/ml, which was significantly
      higher than that in the PBS group [(0.50 +/-0.30)*105/ml, P < 0.01], the number
      of eosinophil in the Der p2 T immunotherapy group decreased significantly [(3.45
      +/- 0.36)*105/ml, P < 0.01]. The content of IFN-gamma in the PBS group, asthma
      group and Der p2 T group were (267.00 +/- 21.98), (155.80 +/- 20.53) pg/ml and
      (234.40 +/- 24.46) pg/ml respectively. Compared with the asthma group, the mice
      with Der p2 T vaccine specific immune treatment produced a high level of IFN
      gamma (P < 0.01). The content of IL-4 in the PBS group, asthma group and Der p2 T
      group were (23.40 +/- 5.96), (53.28 +/- 8.26) pg/ml and (30.00 +/- 5.50) pg/ml
      respectively. Compared with the asthma group, the content of IL-4 in the mice of
      the Der p2 T treatment group was significantly lower (P < 0.01). Compared with
      the asthma group [(308.10 +/- 28.32) pg/ml], the content of IL-13 in BALF of the
      mice in the Der p2 T treatment group was significantly decreased, which was
      [(174.50 +/- 25.99) pg/ml, P < 0.01]. The content of IL-13 in the PBS group was
      (95.99 +/- 31.14) pg/ml. The lung tissue sections showed that the lung
      inflammation in the p2 T Der group was significantly less than that in the asthma
      group, and the inflammatory cell infiltration was significantly decreased, and
      airway epithelial construction remodeled. CONCLUSIONS: The Der p2 T cell fusion
      epitope, which is as vaccines for specific immunotherapy with asthma models, can
      alleviate effectively allergic inflammation of airway and lung in the mice, and
      it may be used as a candidate vaccine for asthma.

PMID- 29469389
TI  - [Development and effectiveness evaluation of time-resolved fluoroimmunoassay kit
      for detection of Schistosoma japonicum].
AB  - OBJECTIVE: To develop a kit of time-resolved fluoroimmunoassay (TRFIA) for
      detection of Schistosoma japonicum protein SjP38, and evaluate its effectiveness.
      METHODS: The anti 9G7 SjP38 monoclonal antibody was used as the capture anti-body
      coated with 96-hole plate, and the Eu3+ labeled 1A6 monoclonal antibody was used
      as the detection antibody to establish the TRFIA SjP38 kit. In addition, the
      accuracy, sensitivity, precision, stability and coincidence rate to pathogenic
      diagnosis of the kit were evaluated. RESULTS: This established kit possessed high
      accuracy, wide linear range from 2 to 1 250 ng/ml, high sensitivity with the
      minimum detectable concentration of 0.14 ng/ml, and good precision (the
      coefficient variation of the intra- and inter-assay were 3.6% to 4.6% and 5.1% to
      6.7%, respectively). The stability tests showed that the reagents could be stable
      for six months at 4 C, 7 d at 37 C. The positive and negative corresponding rates
      to the pathogen detection method were 95% and 100% respectively. CONCLUSIONS: All
      the performance and detection indicators of the kit have reached the requirements
      of clinical test, but its clinical application still needs further validation.

PMID- 29469390
TI  - [Analysis of coagulation related parameters between patients with advanced
      schistosomiasis cirrhosis and hepatitis B cirrhosis].
AB  - OBJECTIVE: To analyze the differences of coagulation parameters between patients
      with advanced schistosomiasis cirrhosis and hepatitis B cirrhosis under different
      degrees of liver function, so as to provide the evidence for further guidance of
      judging clinical condition and prognosis. METHODS: Sixty-three patients with
      advanced schistosomiasis cirrhosis and eighty patients with hepatitis B induced
      cirrhosis hospitalized in Jingzhou Central Hospital from January 2014 to June
      2016 were served as an advanced schistosomiasis cirrhosis group and a hepatitis B
      cirrhosis group, respectively, and ninety-six gastropathy patients excluded from
      other diseases that might affect coagulation in the same period were served as a
      control group. The levels of PT, INR, Fib, TT, APTT, and PLT of the patients
      among the above 3 groups and the cirrhosis patients with different Child-Pugh
      classes were detected and compared. RESULTS: The differences of the levels of PT,
      INR, Fib, TT, APTT, and PLT among the 3 groups were statistically significant (F
      = 84.512, 81.672, 37.612, 104.475, 52.497, 102.233; all P <0.05). The further
      analysis showed that PT, INR, TT, and APTT of both the advanced schistosomiasis
      cirrhosis and hepatitis B induced cirrhosis groups were longer than those of the
      control group, and the PLT levels of both the former 2 groups were lower than
      that of the control group (all P < 0.05). Compared with the advanced
      schistosomiasis cirrhosis group, PT, INR, TT, and APTT of the hepatitis B induced
      cirrhosis group were longer, and the levels of Fib and PLT were lower (all P <
      0.05). Among those with the liver function of Grade A, the reduced degree of PLT
      in the patients with hepatitis B induced cirrhosis was more serious, while for
      those with the liver function of Grade B and C, the difference between the
      patients with advanced schistosomiasis cirrhosis and hepatitis B induced
      cirrhosis was not statistically significant (both P > 0.05). Under all the grades
      of liver function, TT and APTT of the hepatitis B induced cirrhosis group was
      longer than those of the advanced schistosomiasis cirrhosis group, and the Fib
      level of the former was lower than that of the latter. Among those with the liver
      function of Grade A and B, PT and INR of the hepatitis B induced cirrhosis group
      were longer than those of the advanced schistosomiasis cirrhosis group; while for
      those with the liver function of Grade C, the difference between the two groups
      was not statistically significant (all P > 0.05). CONCLUSIONS: There exist
      differences of the damage degrees of coagulation function between the patients
      with advanced schistosomiasis cirrhosis and hepatitis B cirrhosis. When the
      damage degree of the liver function is lighter, the coagulation function in the
      patients with hepatitis B cirrhosis decreases more significantly; when the damage
      degree becomes more severe, APPT in the patients with hepatitis B cirrhosis
      extends more significantly, while the differences of PLT and PT between them are
      little.

PMID- 29469391
TI  - [Thyreophagus entomophagus breeding in beer yeast powder].
AB  - OBJECTIVE: To separate and identify Thyreophagus entomophagus from beer yeast
      powder and observe its morphological characteristics. METHODS: The beer yeast
      powder was collected from the scum after fermentation of the beer material, the
      mites in it were separated and made into slide specimens, and then they were
      identified and observed for the morphological characteristics under an optical
      microscope. RESULTS: The mites separated from the beer yeast powder were
      identified as female Thyreophagus entomophagus. Under the optical microscope, the
      bodies of the mites were long and narrow, which showed an oval shape, the
      gnathosoma was wide, the epidermis was colorless but lustrous, the external
      vertical seta, internal scapular seta, inner humerals, anterior lateral seta, and
      dorsal body setae were all absent, the bristles on the back of the body were
      relatively long, and all the feet were thick and strong. CONCLUSIONS:
      Thyreophagus entomophagus can breed in the beer yeast powder, and therefore, the
      powder should be stored properly to avoid the contamination caused by the mites.

PMID- 29469392
TI  - [Effect of comprehensive schistosomiasis control measures in Kaihua County from
      1996 to 2015].
AB  - OBJECTIVE: To evaluate the control effect of comprehensive measures of
      schistosomiasis after its transmission interruption in Kaihua County, Zhejiang
      Province, so as to provide the references for further consolidation of
      schistosomiasis control. METHODS: The data of Oncomelania hupensis snail survey
      and control, as well as environmental reform in Kaihua County were collected and
      analyzed from 1996 to 2015. RESULTS: From 1996 to 2015, totally 2 635 snail
      habitats and 102.75 hm2 area with snails were found, and 125.4 thousand snails
      were dissected and no one was schistosome infected. The accumulated snail control
      area was 4 932.98 hm2, and the area with snails was effectively reduced by the
      comprehensive control measures. CONCLUSIONS: The schistosomiasis control effect
      could be consolidated by the comprehensive control measures emphasizing
      environmental reconstruction, and the snail surveillance work still should be
      strengthened.

PMID- 29469393
TI  - [Effect of health education of schistosomiasis control with Yi-Han bilingualism].
AB  - OBJECTIVE: To evaluate the intervention effect of Yi-Han bilingual health
      education of schistosomiasis control. METHODS: Baimiao Village in Daqing Town,
      Xichang City, where Yi Nationality inhabited, was chosen as a pilot to carry out
      Yi-Han bilingual health education of schistosomiasis control from 2012 to 2015.
      The villagers and students in the pilot area were investigated by questionnaires
      before and after the intervention to understand their awareness and correct
      behavior status on schistosomiasis control. RESULTS: After the intervention of Yi
      Han bilingual health education of schistosomiasis control for 3 years, the
      awareness rate and the correct rate of behavior on schistosomiasis control of the
      villagers in the pilot area improved from 45.79% and 51.12% in 2012 to 97.80% and
      98.78% in 2015. As for the students, the two rates mentioned above improved from
      64.16% and 60.83% in 2012 to 100% and 98.89% in 2015 respectively, and all the
      differences between the rates before and after the intervention were
      statistically significant (all P < 0.01). CONCLUSIONS: The intervention of Yi-Han
      bilingual health education of schistosomiasis control can obviously improve the
      knowledge awareness rates and the correct rates of behavior of the residents and
      students in the gathering area of Yi Nationality.

PMID- 29469394
TI  - [Pathogen spectrum and epidemic status of major human parasites in Chenzhou City,
      Hunan Province].
AB  - OBJECTIVE: To understand the pathogen spectrum and epidemic status of major human
      parasites in Chenzhou City, Hunan Province, so as to provide the evidence for
      parasitic diseases control. METHODS: The survey sites were selected by the
      stratified cluster sampling method. The intestinal helminthic eggs were detected
      by Kato-Katz technique. The trophozoites or cysts of intestinal protozoa were
      detected by saline smear and iodine staining methods. The eggs of Enterubius
      vermicularis of children from 3 to 6 years old were detected by the cellophane
      anal swab method. The species of hookworm were identified by the filter paper
      strip culture method. RESULTS: A total of 7 031 people were detected with the
      intestinal helminthic infective rate of 1.83% (129 cases). The major parasite was
      hookworm and there was a statistically significant difference of the infection
      rates among various parasites (chi2 = 107.77, P < 0.01). All the hookworm larvae
      were Necator americanus. No intestinal protozoon was detected. There were
      statistically significant differences of the infection rates among the counties
      (chi2 = 25.77, P < 0.01). The age of the patients was mainly focused on 30 and
      above years old and the infection rate was increased with the growth of age (chi2
      = 26.21, P < 0.01). Farmers were the main population of the patients and there
      was a statistically significant difference of the infection rates between farmer
      and others (chi2 = 29.67, P < 0.01). CONCLUSIONS: The infection rates of
      parasites are low and hook-worm is the main parasite in the pathogen spectrum in
      Chenzhou City. However, the infection factors still exist, therefore, effective
      and scientific measures should be taken to consolidate the achievement.

PMID- 29469395
TI  - [Analysis of malaria epidemiological characteristics in Hechi City, Guangxi
      Zhuang Autonomous Region from 2005 to 2015].
AB  - OBJECTIVE: To analyze the epidemiological characteristics of malaria in Hechi
      City, Guangxi Zhuang Autonomous Region from 2005 to 2015, so as to provide the
      evidence for formulating and adjusting measures of malaria elimination. METHODS:
      The data of malaria cases in 11 counties of Hechi City from 2005 to 2015 were
      collected and analyzed by using Micro-soft Office Excel 2003 and SPSS 17.0.
      RESULTS: A total of 160 malaria cases were reported in Hechi City from 2005 to
      2015, and the annual average malaria incidence was 3.6 per million. There were 10
      local recurrence cases (accounting for 6.25%, 10/160) and 150 imported cases
      (accounting for 93.75%, 150/160). For the etiology, Plasmodium vivax accounted
      for 51.87% (83/160) in these cases, P. falciparum accounted for 34.38% (55/160),
      P. ovale accounted for 1.25% (2/160), P. malariae accounted for 5.00% (8/160),
      and the indeterminate accounted for 7.50% (12/160). During the period of 11
      years, the malaria incidence first dropped and then rose. There were no local
      cases after 2009. However, an imported falciparum malaria death case was reported
      in 2010, a severe imported falciparum malaria case was reported in 2013 and
      another in 2015. A severe case of maternal-neonatal vivax malaria was reported in
      2014. These cases were mainly distributed in 10 counties of Hechi City, with more
      young male adults who engaged in digging mining. More cases concentrated from
      April to August. Most of the reported malaria cases were imported, 60.00%
      (96/160) of them returned from Africa and Southeast Asia, and 33.75% (54/160)
      from other domestic provinces. The median of the interval from symptom appearance
      to diagnosis was 5 d, and there was a significant difference among the above
      years (chi2= 33.40, P<0.05). CONCLUSIONS: Malaria is still an important public
      health problem in Hechi City, and the appropriate control measures and effective
      tools should be strengthened for malaria elimination. The key to consolidate the
      achievements of malaria control is strengthening the malaria monitoring
      management of the floating population.

PMID- 29469396
TI  - [Analysis of malaria death cases in Henan Province from 2010 to 2015].
AB  - OBJECTIVE: To retrospectively overview the malaria death cases reported in Henan
      Province and analyze the cause of death. METHODS: The data including basic
      information, epidemiological survey and medical records of malaria death cases in
      Henan Province from 2010 to 2015 were collected and analyzed. RESULTS: In the six
      years, a total of 14 malaria patients were dead. All the death patients were
      adult males and imported from Africa. They had definite histories of living in
      malaria-epidemic areas and the symptoms of fever. Twelve patients were diagnosed
      as malaria after at least twice diagnoses. The average time from symptom
      appearing to correct diagnosis was 6.5 d. The causes of deaths were misdiagnosis
      and delayed treatment. CONCLUSIONS: The major reasons of malaria death cases in
      Henan Province are the failure of correct diagnosis and prompt treatment. Health
      education of malaria prevention and diagnosis and treatment training of malaria
      should be strengthened in order to improve the public awareness and the diagnosis
      ability of clinical doctors for malaria, which can prevent the death of imported
      malaria cases.

PMID- 29469397
TI  - [Evaluation on capability of parasitic disease control and prevention among
      professional and technical personnel in medical and health institutions in Wuxi
      City].
AB  - OBJECTIVE: To understand the capability of parasitic disease control and
      prevention among professional and technical personnel in medical and health
      institutions in Wuxi City, so as to provide the evidence for promoting relative
      capability building. METHODS: Forty-one professional and technical persons from
      22 medical and health institutions received the evaluation through the
      theoretical knowledge exam and laboratory operation skill assessment. RESULTS:
      The average score of theoretical knowledge exam was (76.5+/-15.6) with the pass
      rate of 80.5% and excellent rate of 48.9%. The average score, pass rate and
      excellent rate for Plasmodium blood slide making were (7.3+/-1.5), 87.8% and
      41.5% respectively, the average score, pass rate and excellent rate for
      Plasmodium blood slide reading were (14.0+/-7.2), 31.7% and 12.2% respectively;
      the average score, pass rate and excellent rate for helminthes microscope
      examination were (19.4+/-10.4), 24.4% and 0 respectively; the average score, pass
      rate and excellent rate for Oncomelania hupensis snail identification were (8.6+/
      1.1), 95.1% and 73.2% respectively. The average scores of helminthes microscope
      examination and Oncomelania hupensis snail identification were higher in the
      participants with middle-level professional title or above than in the
      participants with primary level professional title (both P < 0.05). The average
      scores of theoretical knowledge exam, Plasmodium blood slide reading and
      helminthes microscope examination were higher in the participants from disease
      control and prevention institutions than in the staff who came from medical
      institutions (all P <0.05). CONCLUSIONS: The professional and technical personnel
      in medical and health institutions in Wuxi do better in theoretical knowledge,
      Plasmodium blood slide making and Oncomelania hupensis snail identification.
      However, the capability of parasite microscope examination is urgently needed to
      be improved in the future.

PMID- 29469398
TI  - [Investigation of soil - transmitted nematode infections in Xiding Township,
      Menghai County, Yunnan Province].
AB  - OBJECTIVE: To understand the status of soil-transmitted nematode infections in
      Xiding Township, Menghai County, Yunnan Province, so as to provide the reference
      for formulating the strategy of soil-transmitted nematodosis control. METHODS:
      Soil-transmitted nematode eggs in feces were detected by the Kato-Katz method,
      and the eggs of Enterobius vermicularis were detected by the cellophane tape
      method in children. The soil samples were collected from vegetable, fruit and
      other crop fields of 15 residents randomly to detect hookworm. RESULTS: The stool
      samples from 1 002 residents were examined and the soil -transmitted nematode
      infection rate was 20.06% (201/1 002). The infection rates of hookworm, Ascaris
      lumbricoides and Trichuris trichura were 18.96% (190 cases), 1.70% (17 cases) and
      0.90% (9 cases) respectively. The percentages of people with light infection of
      hookworm, A. lumbricoides and T. trichura were 97.37% (185/190), 88.24% (15/17)
      and 100% (9/9) respectively. No infection of E. vermicularis was found. Fifteen
      soil samples were tested, and no hookworm was found in the soil. CONCLUSIONS: The
      infection rate of soil-transmitted nematode in Xiding Township, Menghai County is
      high, but the infectiosity is light. The control and monitoring of soil
      transmitted nematodosis should be strengthened in this area.

PMID- 29469399
TI  - [Investigation of knowledge, attitude and practice (KAP) of foodborne parasitic
      diseases among senior high school students in Zigui County].
AB  - OBJECTIVE: To understand the status of knowledge, attitude and practice (KAP) of
      foodborne parasitic diseases among senior high school students in Three Gorges
      Reservoir Region. METHODS: A total of 1 353 senior high school students were
      selected with the cluster sampling method and investigated with the
      questionnaires in Zigui County, and the data were analyzed statistically.
      RESULTS: Among the 1 353 students surveyed, the awareness rates of parasitic
      diseases, their hazards and transmissions were 62.23% (842 cases), 80.78% (1 093
      cases) and 83.89% (1 135 cases) respectively. The awareness rate of parasitic
      diseases in the students of senior Grade One was higher than that of Grade Two
      (chi2 = 7.037, P < 0.05). The formation rates of behaviors of refusing of raw
      food, refusing of unboiled water, and dining at home or school in the students of
      senior Grade One were higher than those of Grade Two (chi2 = 6.970, 12.749 and
      12.921 respectively, and all P < 0.05). Fifty-one percent (690 cases) of students
      would not have the food with the infection risk of parasitic diseases.
      CONCLUSIONS: The awareness of parasitic diseases of high school students in Zigui
      County is not efficient, and the health education should be strengthened.

PMID- 29469400
TI  - [Analysis of capabilities of microscopic examinations of Plasmodium in Dongxihu
      District, Wuhan City].
AB  - OBJECTIVE: To investigate and analyze the capabilities of Plasmodium microscopic
      examinations in medical and health organizations in Dongxihu District, Wuhan
      City, so as to provide evidences for achieving the standard of malaria
      elimination and malaria control in the future. METHODS: The basic information of
      the laboratorians and the hardware facilities in 15 microscopic examination
      stations of Plasmodium were collected and analyzed from 2010 to 2015. Meanwhile,
      the quality of making, dyeing, cleanliness of all the negatives blood smears were
      evaluated, and all the positive smears were re-checked in the district during the
      period above mentioned. RESULTS: Totally, there were 28 laboratorians and 9
      qualified microscopes in 15 microscopy stations in Dongxihu District. The age of
      the laboratorians in the first-level and third-level organizations was mainly
      from 40 to 50 years old, but the age of those in the second-level organizations
      was from 20 to 30 years old. The years for microscopic examination working of
      most of the laboratorians in the first-level and third-level organizations were
      more than 15 years, while the working years of those in the second-level
      organizations were mainly less than 10 years. The education level of the
      laboratorians in the first-level organization was mainly (50.00%) junior college,
      while the education levels of those in the second and third organizations were
      mainly bachelor. From 2010 to 2015, 8 561 blood smears were produced and 539 of
      them were reviewed, the coincidence rates of review were all 100%, and the
      average qualified rates of making, dyeing, and cleanliness of the negative blood
      smears were 82.08%, 79.92% and 83.33%, respectively. All the rates mentioned
      above in 2015 were higher than those in 2010 (chi2 = 26.45, 16.85, 13.93, all P <
      0.01). CONCLUSIONS: The capability of microscopic examinations of Plasmodium has
      improved obviously in Dongxihu District, but the human resources construction and
      hardware input in this district should be improved, meanwhile, the check on the
      quality control of microscopic examinations of Plasmodium should be continued, so
      as to guarantee the sustainable and healthy development of malaria control work
      in this district.

PMID- 29469401
TI  - [Discussion on multidisciplinary treatment mode of advanced schistosomiasis and
      its standardized implementation].
AB  - Advanced schistosomiasis is the most serious clinical type of schistosomiasis.
      Its diagnosis and treatment are related to many special departments, such as
      gastroenterology, general surgery, neurology, endocrinology, radiology,
      traditional Chinese medicine, blood purification, endoscopy, intervention, and
      ICU. It is necessary to apply a multidisciplinary treatment (MDT) mode. However,
      the mode has no universal standard and guide in practice. It is very important
      for the implementation of MDT mode of advanced schistosomiasis to form a
      treatment expert team, formulate the formal working procedures, and standardize
      the treatment schedules. The standardized implementation of MDT mode will be
      important to provide a more effective clinical decision on advanced
      schistosomiasis.

PMID- 29469402
TI  - [Schistosomiasis endemic situation of national surveillance sites in Mianyang
      City, 2015].
AB  - OBJECTIVE: To master the dynamics of schistosomiasis endemic situation and
      influencing factors in Mianyang City, so as to provide the evidence for making
      the control and prevention measures. METHODS: Six villages of six schistosomiasis
      heavy endemic counties were selected as survey sites according to the national
      surveillance protocol (Revision in 2014) in Mianyang City. The surveys of the
      incidences of schistosomiasis in population and livestock as well as the
      prevalence of Oncomelania hupensis snails were conducted in the 6 national
      surveillance sites. RESULTS: The serum positive rates of local residents and
      migrant people were 2.12% and 1.71%, respectively. The infection rate of cattle
      was 0. The area with snails was 9.344 8 hm2. The mean density of living snails
      was 0.25/0.1 m2. The occurrence rate of frames with snails was 7.07%, and no
      infected snails were found. CONCLUSIONS: The infection rates of schistosome in
      human and livestock are low and the prevalence of O. hupensis snails is stable in
      the national surveillance sites in Mianyang City. However, the schistosomiasis
      transmission risk still exists, therefore, we should strengthen the control
      measures to prevent the rebound of the endemic.

PMID- 29469403
TI  - [Diagnosis and treatment of an imported case of schistosomiasis haematobium].
AB  - OBJECTIVE: To report the diagnosis and treatment of an imported case of
      schistosomiasis haematobium, including the pathological features of the disease
      and therapeutic efficacy of praziquantel. METHODS: The data of the patient with
      schistosomiasis haematobium were collected, and the pathological features of the
      bladder tissue were observed under a microscope. More-over, the patient was
      treated with praziquantel, and his urine was collected before and after the
      treatment. The eggs in the urine were examined by a microscope after sediment and
      the miracidia were hatched. RESULTS: The patient once worked in Angola for three
      months, and after returning home he had the symptoms of intermittent painless
      terminal hematuresis. It was ineffective after anti-inflammatory treatment in a
      number of hospitals. There were no sand spots discovered under the cystoscope.
      However, the inflammatory reaction to parasite with a lot of eosinophils
      infiltration in the bladder mucosa was found on the pathological sections under a
      microscope, and the egg structure was observed with individual characteristics.
      The eggs were detected in the urine and the miracidia were hatched before the
      praziquantel treatment. The hematuria symptoms disappeared after the praziquantel
      treatment. The eggs were still detected in the urine 7 days post-treatment, but
      the miracidium could not be hatched. One month and 6 months post-treatment, the
      eggs were not detected in the urine. CONCLUSIONS: The imported cases of
      schistosomiasis haematobium are often misdiagnosed, and therefore, it is
      necessary to strength the health education to the workers overseas and also to
      improve the ability of diagnosis in medical staff. For the case reported in this
      paper, there are typical structure of Schistosoma haematobium eggs and egg
      granulomas on the pathological sections of bladder tissues. Praziquantel has
      satisfactory treatment results.

PMID- 29469404
TI  - [Discussion on ultrasonographic characteristics of schistosomal appendicitis
      lesions].
AB  - OBJECTIVE: To discuss the ultrasonographic characteristics of schistosomal
      appendicitis lesions. METHODS: Among the patients with schistosomal hepatopathy
      who were discovered by Color Doppler ultrasound in Huzhou Central Hospital from
      January 2012 to December 2015, 50 cases with clear history of schistosomiasis and
      treatment were chosen as a schistosomal hepatopathy group, meanwhile, 50 normal
      people, who came from non-endemic areas, without schistosomal hepatopathy and
      schistosomiasis history were chosen as a control group. The two groups were
      examined by ultrasound scan of the appendix, and the data of the largest diameter
      of the appendix and the thickness of the appendix wall were collected, and the
      sonographic characteristics of their appendixes, such as whether the echo of the
      appendix wall was even or not, were observed. RESULTS: The minimum internal
      diameter of the appendix cavity and the thickness of the appendix wall of the
      schistosomal hepatopathy group were (2.090 +/- 0.790) mm and (1.332 +/- 0.313)
      mm, respectively, the former was significantly narrower than that of the control
      group, while the latter was significantly thicker than that of the control group
      (t = 2.647, - 4.526, respectively, both P<0.05). The proportions of those with
      inhomogeneous echo, indistinctness structure, uneven thickening of the appendix
      wall, as well as having intestinal contents in the appendix cavity in the
      schistosomal hepatopathy group were higher than those in the control group (chi2
      = 12.000, 18.537, 24.008, 4.244, respectively, all P<0.05). CONCLUSIONS:
      Schistosomal appendicitis lesions have obvious ultrasonographic characteristics
      under ultrasound. Ultrasound can play an important role in judging whether the
      appendix of schistosomiasis patients is involved and discovering the lesion of
      appendix early.

PMID- 29469405
TI  - [Serological survey on Toxoplasma gondii infection in pregnant women with history
      of adverse pregnancy in Bazhou area, Hebei Province].
AB  - OBJECTIVE: To investigate the Toxoplasma gondii infection status in pregnant
      women with history of adverse pregnancy and risk factors in Bazhou area, Hebei
      Province. METHODS: A total of 302 pregnant women with the history of adverse
      pregnancy were chosen as respondents (an experimental group) in the hospital from
      March 2012 to December 2015, and 197 pregnant women without the history of
      adverse pregnancy as a control group. TOX-IgG and TOX-IgM were detected by using
      ELISA in two groups. The risk factors of Toxoplasma infection were surveyed by
      questionnaires. RESULTS: The total positive rate of Toxoplasma antibodies was
      28.15% (85/302) in the experimental group, which was significantly higher than
      that [9.64%(19/197)] in the control group, and the difference was statistically
      significant (chi2 = 24.76, P<0.05). The positive rates of TOX-IgM, TOX-IgG and
      TOX-IgM + TOX-IgG were 6.95% (21/302), 18.54% (56/302), and 2.65% (8/302)
      respectively in the experimental group, which were higher than 2.03% (4/197),
      7.61% (15/197), and 0% (0/197) respectively in the control group (chi2 = 6.07,
      11.67, 3.76, all P<0.05). The questionnaire survey showed that the proportions of
      keeping pets, cutting board regardless, liking to eat hot pot or barbecue, eating
      raw meat, often eating in the restaurant in the pregnant women with Toxoplasma
      infection were higher than those in the pregnant women without Toxoplasma
      infection, and the differences were statistically significant (chi2 = 22.57,
      3.96, 5.87, 7.40, 4.86, all P<0.05), and therefore, the above unhealthy habits
      may be important risk factors. CONCLUSIONS: Toxoplasma infection could lead to
      adverse pregnancy outcomes. Therefore, the above-mentioned unhealthy habits
      should be avoided, especially during pregnancy period.

PMID- 29469406
TI  - [Immunomodulatory effects of Treg and Th17 cells in parasitic infections and
      hygiene hypothesis].
AB  - The parasitic infection is still a severe public health problem in developing
      countries, which threatens people's health and social development. With the
      advances of molecular biology and immunology, more and more insights have been
      reached on the immunity and immunopathogenesis to parasitic infections. CD4+ T
      cells play a central role in the host's immunosurveillance and immunoregulation.
      Traditionally, naive CD4+ T cells are considered to be able to differentiate into
      Th1 and Th2 cell subsets both in vivo and in vitro. These Th1 and Th2 cells
      secret diverse cytokine profiles to exert different functions. Later, two new
      subsets of CD4+ T cells, Th17 and Treg cells, have been discovered. They are
      completely different from traditional Th1 and Th2 cells with independent
      differentiation and regulation mechanism. Ample studies suggest that Treg and
      Th17 cells play a key role in a variety of parasitic diseases. Furthermore, Treg
      and Th17 cells have been got increasing attention for their involvement in the
      hygiene hypothesis. Based on the current advances of researches of Treg and Th17
      cells, we make a brief review about immunomodulatory effects of these two subsets
      in parasitic infections as well as the hygiene hypothesis.

PMID- 29469407
TI  - [Advances in researches of biogenic molluscicides].
AB  - Biogenic molluscicides refer to the use of plants, animals and micro-organisms or
      their metabolites, and synthesis biomimetic molluscicides to kill Oncomelania
      hupensis snails. With the rapid development of science and technology, new
      biogenic molluscicides are continuously emerging and the category also continues
      to expand. According to the molluscicidal active ingredient and sources, at
      present, the biogenic molluscicides with in-depth studies include plant-derived
      molluscicides, micro-organism molluscicides, microbial metabolite molluscicides
      and animal molluscicides. This paper reviews the advances in the researches of
      biogenic molluscicides in recent years.

PMID- 29469408
TI  - [One case of Gongylonema pulchrum infection in esophagus in human].
AB  - This paper reports one case of Gongylonema pulchrum infection in the esophagus in
      human.

PMID- 29469409
TI  - [Epidemic situation and prevention and control strategy of clonorchiasis in
      Guangdong Province, China].
AB  - Clonorchiasis is one of the food-borne parasitic diseases. Adult parasites live
      in the human liver and gallbladder tube system, causing serious complications,
      such as gallstones, cholecystitis and cholangitis, and even bile duct cancer. The
      disease is very popular in our country, and the population infection rate is
      high. It is an important public health problem. Guangdong Province is the
      earliest province being found of clonorchiasis and with serious epidemic. In the
      second national human parasitic diseases distribution survey, the results showed
      that the average infection rate of Clonorchis sinensis in the epidemic areas in
      Guangdong was 16.42%. It is estimated that the population of C. sinensis
      infection is over 6 million. The prevention and control of clonorchiasis in China
      is still in the initial stage currently and we face many challenges such as
      unclear epidemic characteristics and transmission mode, and lack of long-term
      prevention and control mechanism. This article introduces the epidemic situation
      of clonorchiasis and prevention and control strategies and measures in Guangdong.

PMID- 29469410
TI  - [Analysis of Oncomelania hupensis snail situation in schistosomiasis surveillance
      sites in Hubei Province from 2009 to 2014].
AB  - OBJECTIVE: To analyze the Oncomelania hupensis snail situation in schistosomiasis
      surveillance sites in Hubei Province from 2009 to 2014. METHODS: From 2009 to
      2014, 207 schistosomiasis endemic villages from 13 cities were selected as the
      surveillance sites in Hubei Province, where the surveillance of snail situation
      was performed, and the data about the indexes of snail situation during the 6
      years were collected and analyzed statistically. RESULTS: From 2009 to 2014,
      totally 80 963.47 hm2 of snail areas were investigated, and 45 309.77 hm2 of area
      with snails as well as 364.93 hm2 of area with infected snails were found out,
      and 1 646 125 snails were captured. In the 207 surveillance sites, the density of
      living snails was reduced from 0.493 3 snail/0.1 m2 in 2009 to 0.339 3 snail/0.1
      m2 in 2014, with a decline rate of 31.22%; the density of infected snails was
      reduced from 0.000 7 snail/0.1 m2 in 2009 to 0 in 2014; the infection rate of
      snails was reduced from 0.14% in 2009 to 0 in 2014. The infection rates of snails
      in the third-rank villages, endemic areas in inner embankment, ditch environment
      and weed environment were relatively higher. CONCLUSIONS: The snail situation of
      Hubei Province has been declined steadily. However, the environment of snail
      breeding has not been changed completely. In order to consolidate the control
      achievements further, the measures including mollusciciding and snail control
      projects should be strengthened.

PMID- 29469411
TI  - [Molluscicidal effect of niclosamide ethanolamine salt powder - granula against
      Oncomelania hupensis].
AB  - OBJECTIVE: To evaluate the molluscicidal effect of niclosamide ethanolamine salt
      powder-granula (PG) against Oncomelania hupensis. METHODS: The molluscicidal
      experiment was carried out by the dusting method with niclosamide ethanolamine
      salt 4% PG. The experiments were respectively done in the laboratory and the
      tidal flats wetlands. At the same time, the niclosamide ethanolamine salt 4%
      dustable powder (DP) was as the control group. The single blind method was used
      for the quality control. The corrected mortality and the median lethal
      concentration (LC50) were compared between PG and DP in the molluscicidal
      experiment of the laboratory. The corrected mortality and the reduced rate of
      snails'density were compared between PG and DP in the tidal flats wetlands.
      RESULTS: The mortality rates of the snails were 96.67% and 100% respectively on 1
      d after dusting 4.0 g/m2 of 4% PG and 2.0 g/m2 of 4% DP in the laboratory. The
      results showed that the mortality rates of the snails were higher with 4% DP than
      4% PG in each dosage (t1 d = 3.60, P < 0.01). The LC50 (s) of 1d, 3 d, 7 d after
      dusting the molluscicide also showed that the molluscicidal effects of DP were
      better than PG. The corrected mortality rates were 91.71%, 92.91%, 90.57%, 85.33%
      and 71.09%, 90.11%, 90.13%, 85.26% on 3 d, 7 d, 15 d, 30 d after dusting with 4%
      PG and 4% DP, respectively, in the fields. Statistics showed that the mortality
      rates of snails were higher on 3 d, 7 d after dusting with PG than DP (chi23 d =
      731.57, chi27 d = 25.90, P < 0.01), but there were no significant differences
      between PG and DP on 15d, 30d after dusting (chi215 d = 0.53, chi230 d = 0.01, P
      > 0.05). CONCLUSIONS: 4% PG has both the adsorption of powder and the
      penetrability of the granules. The molluscicidal effects of 4% PG and 4% DP are
      almost the same. However, the drift of the powder was still not effectively
      controlled. This problem need to be further studied.

PMID- 29469412
TI  - [Application of automatic photography in Schistosoma japonicum miracidium
      hatching experiments].
AB  - OBJECTIVE: To explore the value of automatic photography in the observation of
      results of Schistosoma japonicum miracidium hatching experiments. METHODS: Some
      fresh S. japonicum eggs were added into cow feces, and the samples of feces were
      divided into a low infested experimental group and a high infested group (40
      samples each group). In addition, there was a negative control group with 40
      samples of cow feces without S. japonicum eggs. The conventional nylon bag S.
      japonicum miracidium hatching experiments were performed. The process was
      observed with the method of flashlight and magnifying glass combined with
      automatic video (automatic photography method), and, at the same time, with the
      naked eye observation method. The results were compared. RESULTS: In the low
      infested group, the miracidium positive detection rates were 57.5% and 85.0% by
      the naked eye observation method and automatic photography method, respectively
      (chi2 = 11.723, P < 0.05). In the high infested group, the positive detection
      rates were 97.5% and 100% by the naked eye observation method and automatic
      photography method, respectively (chi2 = 1.253, P > 0.05). In the two infested
      groups, the average positive detection rates were 77.5% and 92.5% by the naked
      eye observation method and automatic photography method, respectively (chi2 =
      6.894, P < 0.05). CONCLUSIONS: The automatic photography can effectively improve
      the positive detection rate in the S. japonicum miracidium hatching experiments.

PMID- 29469413
TI  - [Evaluation on application of China Disease Prevention and Control Information
      System of Hydatid Disease I Current status at the provincial level].
AB  - OBJECTIVE: To evaluate the application status of China Disease Prevention and
      Control Information System of Hydatid Disease, in which questions existed are
      summarized in order to promote the system update. METHODS: A questionnaire was
      designed and distributed to Inner Mongolia, Sichuan, Tibet, Gansu, Qinghai,
      Ningxia, Xinjiang and Xinjiang Production and Construction Corps to evaluate the
      application status of China Disease Prevention and Control Information System of
      Hydatid Disease assistant with telephone. RESULTS: The recovery rate of
      questionnaires was 87.5%. The statistics of closed questions showed that national
      application rate of the China Disease Prevention and Control Information System
      of Hydatid Disease was 100%, of which 15.3% were low frequency users, 57.1%
      believed the system was necessary, 28.6% considered it was dispensable, and 14.3%
      believed that it was totally unnecessary. The statistics of open-ended questions
      indicated that 6 endemic regions suggested to increase the guidance and training,
      while 4 endemic regions had opinions on sharing the information of the national
      infectious disease reporting systems and hydatid disease prevention and control
      information system, and the opinions on turning monthly report to quarterly
      report, and increasing statistics and analysis module, and 3 endemic regions
      deemed that the system had logic errors and defects. CONCLUSIONS: The problems of
      the system are mainly focused on the existence of systemic deficiencies and logic
      errors, lacking of statistical parameters and corresponding analysis function
      module, and lacking of the guidance and training, which limits the use of the
      system. Therefore, these problems should be resolved.

PMID- 29469414
TI  - [Epidemiological analysis of malaria prevalence in Hubei Province from 2010 to
      2014].
AB  - OBJECTIVE: To understand the malaria epidemic situation in Hubei Province from
      2010 to 2014, so as to provide the evidence for formulating the effective malaria
      elimination strategies and measures in this province. METHODS: The data from the
      Disease Reporting Information System of Chinese Center for Disease Control and
      Prevention were collected and analyzed with the descriptive epidemiological
      method for the epidemiological characteristics of malaria in Hubei Province from
      2010 to 2014. RESULTS: A total of 997 malaria cases were reported in Hubei
      Province from 2010 to 2014, there were 618 cases of vivax malaria, 352 cases of
      falciparum malaria, 18 cases of Plasmodium ovale infection, and 9 cases of
      Plasmodium malariae infection. Among all the reported cases, 479 were local cases
      and 518 were imported cases. No local malaria cases were reported from Hubei
      Province since 2013. The overall imported malaria cases showed a gradual
      increasing trend from 2010 to 2014, the proportion of falciparum malaria
      increased quite significantly from 2010 to 2014. The malaria cases were mainly
      distributed in Xiangyang, Wuhan, Xiaogan, Yichang, Jingmen and Suizhou cities,
      reaching 81.85% of the cases of the whole province. There were 810 male cases and
      187 female cases, with a sex ratio of 4.33:1. The local malaria cases were mainly
      aged from 40 to 69 years, accounted for 78.29% of the total local cases, and
      88.22% (457/518) of the whole local cases were concentrated in 20-49 age groups.
      The local cases were mainly farmers (67.01%). Among the imported malaria cases,
      the occupation distribution concentrated mainly on the worker, migrant worker,
      and farmer (63.90%). CONCLUSIONS: The local malaria epidemic situation has been
      effectively controlled in Hubei Province, which reflects the initiative
      achievements of malaria elimination. However, there are still many imported
      malaria cases from abroad. Therefore, the imported malaria from abroad still
      remains the key of malaria control in Hubei Province.

PMID- 29469415
TI  - [Epidemiological analysis of imported malaria cases in 20 counties at border
      region of Yunnan Province from 2012 to 2014].
AB  - OBJECTIVE: To analyze the epidemiological characteristics of the imported malaria
      cases in 20 counties at the border region of Yunnan Province from 2012 to 2014,
      so as to provide the evidence-based proof for adjusting the strategies in the
      elimination stage. METHODS: The malaria epidemic data of the 20 border counties
      in Yunnan Province from 2012 to 2014 were collected and analyzed by using
      Microsoft Excel 2010. RESULTS: From 2012 to 2014, a total of 1 558 malaria cases
      were reported in the 20 border counties in Yunnan Province, among which, 1 336
      were imported cases, accounting for 85.75% (1 336/1 558), and 222 were indigenous
      cases, accounting for 14.25% (222/1 558). The number of the imported cases in the
      above years took up 80.00% (544/680), 89.10% (425/477) and 91.52% (367/401) of
      the total reported cases in the whole year, respectively. Among all the 1 336
      imported cases, 1 045 (78.22%) were infected with Plasmodium vivax, 284 (21.26%)
      were infected with P. falciparum, 3 were infected with P. malariae, 3 were mixed
      infection and 1 was an unclassified case; 2 patients died. And 95.58% of the
      cases were mainly infected in Myanmar (1 277 cases). Young and middle-aged adult
      of 20-40 years who worked overseas were the predominant (802 cases, 60.03%) and
      most of the cases occurred from April to June of the year (679 cases, 50.82%).
      Those cases mainly distributed in Tengchong (459 cases), Ruili (366 cases),
      Yingjiang (191 cases) and Mangshi (78 cases). CONCLUSIONS: The epidemic situation
      of imported malaria is serious in the border region of Yunnan Province.
      Therefore, the surveillance system of malaria control needs to be well planned
      and managed to ensure timely case detection and prompt response at the
      elimination and post-elimination stage.

PMID- 29469416
TI  - [Diffusion, population dynamics and potential distribution of Armigeres
      subalbatus].
AB  - OBJECTIVE: To investigate the diffusion trend of Armigeres subalbatus and analyze
      its potential geographic distribution in China. METHODS: The trend analysis of
      diffusion and population dynamics were carried out based on three aspects
      including literature reports, information of museum specimens and new collection
      records from our field survey. To compare the potential geographic distribution,
      two ecological niche models were constructed by Maxent software based on the
      geographic presence occurrence data and 20 environmental variables. The final
      models were evaluated with the receiver operating characteristics curve (ROC).
      The analyses of variable contributions were confirmed by using the Jackknife
      method. RESULTS: The populations in Weifang and Weihai, Shandong Province were
      reported for the first time. The results showed that this species was spread to
      the Palaearctic Northern Region and reached 42 degrees  north latitude regions.
      In some areas, it gradually developed into a dominant species. A total of 294
      georeferenced occurrence points of A. subalbatus were found out. Two predictions
      of Maxent models were established based on the presence occurrence data in 2000
      and 2016, respectively. The results showed that the current distribution range of
      A. subalbatus had been significantly northward expanded compared with 2000. It
      means that the potential suitable area gradually spread northward. The ROC
      analysis results showed the AUC values were 0.980 and 0.982, and it indicated
      that the models had a high reliability. The Jackknife method displayed that the
      precipitation of warmest quarter, precipitation of wettest month and
      precipitation of wettest quarter were the dominant environmental variables that
      mainly contributed to the distribution of A. subalbatus. CONCLUSIONS: A.
      subalbatus distribution gradually spreads northward, and climate warming is
      probably the main reason for the diffusion. It could affect the local mosquito
      species composition and increase the risk of mosquito-borne disease transmission.

PMID- 29469417
TI  - [Effect evaluation of three ELISA kits in detection of paragonimiasis].
AB  - OBJECTIVE: To evaluate the effects of 3 kinds of ELISA reagents on the detection
      of human paragonimiasis. METHODS: A total of 45 serum samples from patients with
      paragonimiasis, 218 serum samples from patients with other parasitic diseases as
      well as 80 serum samples from healthy people were detected by GD-ELISA (IgG
      antigen ELISA detection reagent), ESELISA (using excretory/secretory (ES)
      products of Paragonimus westermani), and sAg-ELISA (using semi-purified antigen
      (sAg) of P. westermani), respectively. The effects of the 3 reagents were
      evaluated and compared. RESULTS: The sensitivities of GD-ELISA, ES-ELISA, and sAg
      ELISA were 95.6% (95% CI:89.6%~100.0%), 93.3% (95% CI:86.0%~100.0%) and 86.7%
      (95% CI:76.8%~96.6%), respectively; the specificities of the above three reagents
      were 88.6% (95% CI:85.0%~ 92.2%), 88.9% (95% CI:85.3%~92.5%) and 99.0 % (95%
      CI:97.9%~100.0%), respectively, and the Youden indexes of them were 0.84, 0.82
      and 0.86, respectively. CONCLUSIONS: sAg-ELISA is more suitable than GD-ELISA and
      ES-ELISA for clinical sample tests in paragonimiasis endemic areas in China.

PMID- 29469418
TI  - [Effect and mechanism of CD4+CD25+ regulatory T cells on protective efficacy of
      protein vaccine against Schistosoma japonicum in mice].
AB  - OBJECTIVE: To explore the effect and mechanism of CD4+CD25+ Tregs (Tregs) on the
      protective efficacy of gluthatione-S-transferase (GST) against Schistosoma
      japonicum in mice. METHODS: Female BALB/c mice were divided randomly into five
      groups:a normal control group, an infected control group, an anti-CD25mAb group,
      a GST immunization group and a combination group with GST immunization and anti
      CD25 mAb. The GST group and combination group were injected percutaneously with
      GST 50 MUg each mouse, the other two groups were injected with equal volume PBS.
      The immunization was performed for 3 times for two-week interval, and 2 weeks
      after the last immunization, each mouse was challenged with 40 S. japonicum
      cercaria. Two weeks post-infection, the combination group and anti-CD25 mAb group
      were injected intraperitoneally with 300 MUg antiCD25 mAb each mouse. The mice
      were succumbed 2 weeks, 3 weeks, 4 weeks and 5 weeks post-infection respectively.
      The percentages of CD4+CD25+ Tregs in splenocytes of mice were measured with flow
      cytometer. The levels of IFN-gamma, IL-2, IL-4, IL-5 and TGF-beta in cell
      cultural supernatants were determined by sandwich-ELISA after stimulation with
      Con A. The liver sections were stained with hematoxylin and eosin. RESULTS: The
      worm burden in the combination group (15.80+/-2.74) was significantly lower than
      those of the infected control group (27.78+/-3.15), anti-CD25 mAb group (21.50+/
      4.21), and GST group (20.84+/- 6.46). Compared to those of the infected control
      group, the percentages of CD4+CD25+ Tregs were significantly higher in the GST
      group, while the percentages of CD4+CD25+ Tregs were significantly lower post
      anti-CD25 mAb-administration. Regardless of GST administration, the levels of IFN
      gamma, IL-2, IL-4 and IL-5 after anti-CD25 mAb were significantly higher than
      those of the infected control groups. There were no significant differences of
      egg granuloma and the level of TGF-beta between each group. CONCLUSIONS:
      CD4+CD25+ Tregs could be partially blocked by anti-CD25 mAb while Th1 and Th2
      type immunization response could be enhanced, which plays a role in improving the
      protective efficacy of GST against of S. japonicum.

PMID- 29469419
TI  - [Correlation between genetic differences of mates and pathogenicity of
      Schistosoma japonicum in definitive host].
AB  - OBJECTIVE: To explore the correlation between the genetic dissimilarity and
      heterozygosity of mates and the pathogenicity of Schistosoma japonicum in the
      definitive host. METHODS: By using seven microsatellite loci markers, S.
      japonicum genotyping of sixteen pairs randomly mated was performed, the genetic
      dissimilarity and heterozygosity were calculated between the mates, and the
      correlation between the genetic dissimilarity and heterozygosity of the mates and
      the pathogenicity of S. japonicum in the definitive host was evaluated. RESULTS:
      There was a significant correlation between the genetic similarity of S.
      japonicum mates and the mean number of eggs per worm pair in the liver and
      intestinal tissue (r = 0.501 6, P < 0.05; r = 0.796 5, P < 0.01, respectively)
      and the hatching rate of deposited eggs in the liver (r = 0.508 3, P < 0.05),
      respectively. There was no correlation between the genetic similarity of the
      mates and hepatosplenomegaly per worm pair (r = 0.109 5, P > 0.05; r = 0.265 3, P
      > 0.05, respectively) and the average diameter of granuloma in the liver (r = 
      0.272 7, P > 0.05), respectively. There was no correlation between the
      heterozygosity of the mates and all the pathological parameters of S. japonicum
      in the definitive host (P > 0.05). CONCLUSIONS: There is the correlation between
      the genetic dissimilarity of the mates and the pathogenicity of S. japonicum in
      the definitive host, and the genetic dissimilarity is greater, pathogenicity is
      weaker. There is no correlation between heterozygosity of the mates and the
      pathogenicity of S. japonicum in the definitive host.

PMID- 29469420
TI  - [Culture and characterization of spontaneous ascites cells isolated from Microtus
      fortis].
AB  - OBJECTIVE: To isolate and culture the spontaneous ascites cells from Microtus
      fortis under artificial conditions, so as to investigate the molecular mechanism
      at the cell level. METHODS: The cells were isolated from spontaneous ascites of
      M. fortis artificially bred for 90 d, and were cultured and observed under a
      microscope. The differences of ascites cells among normal, spontaneous ascites
      and schistosomiasis infected samples of M. fortis were compared. The lesion of
      tissue was observed simultaneously. RESULTS: There were no obvious organ tissue
      lesions in M. fortis with spontaneous ascites, and the number and types of cells
      in peritoneal fluid were irregular and significantly changed. With the extension
      of culture time, the colonies appeared and there were a large number of vacuole
      like cells in the cultured medium and sequentially presenting proliferation,
      deformation, disintegration and the fiber-like changes and could be passaged 3-4
      d only. CONCLUSIONS: The cells from M. fortis with spontaneous ascites are
      similar to its abdominal cavity cells after infection of Schistosoma japonica.

PMID- 29469421
TI  - [Identification of two Bithynia species from Heng County, Guangxi Zhuang
      Autonomous Region, China by using morphological and DNA barcoding methods].
AB  - OBJECTIVE: To distinguish two Bithynia species, Bithynia fuchsiana and Bithynia
      robusta collected from Heng County, Guangxi Zhuang Autonomous Region, by using
      morphological and DNA barcoding methods. METHODS: The adult B. fuchsiana and B.
      robusta were collected from the biotope such as rivers, ditches and ponds in Heng
      County of Guangxi Zhuang Autonomous Region, China. The two species specimens were
      identified by measuring shell morphological parameters, comparing the characters
      of the male reproductive system, and using the COI gene barcoding technique and
      building phylogenetic tree. RESULTS: B. fuchsiana and B. robusta were similar
      morphologically in the shell appearance; they had the similar snail height, snail
      width, shape and male reproductive structure. The DNA sequence analysis showed
      that the COI gene of the two Bithynia species had low sequence divergence with 11
      variation sites among 22 sequences. The length of the COI gene segment was 517 bp
      and no insertion sites and deletion loci after sequence edited. All individuals
      of the two species gathered to one clade in the phylogenetic tree based on COI
      gene. CONCLUSIONS: According to the evidence of morphology and COI gene coding
      sequence, B. fuchsiana and B. robusta from Heng County, Guangxi Zhuang Autonomous
      Region, are likely to be the same species.

PMID- 29469422
TI  - [Cloning, fusion expression and identification of thioredoxin encoding gene from
      Toxoplasma gondii].
AB  - OBJECTIVE: To clone and express the thioredoxin (Trx) from RH strain tachyzoites
      of Toxoplasma gondii, establish the prokaryotic expression vector and purify the
      recombinant protein, then produce the polyclonal anti-Trx antibody in rabbits.
      METHODS: Trx fragment was amplified by PCR and cloned into the pET-28a (+)
      vector, and the recombinant protein was induced with IPTG and purified by Ni-NTA
      affinity chromatography. The polyclonal antibody specificity was detected by
      Western blotting. RESULTS: The trx gene was amplified from T. gondii cDNA by PCR.
      The recombinant plasmid trx/pET-28a (+) was usefully constructed, and the
      recombinant TRX protein was expressed and purified. The TRX polyclonal antibody
      was also obtained. The specific band of TRX was detected by Western blotting.
      CONCLUSIONS: Western blotting can detect the specificity of polyclonal anti-Trx
      antibody, which will facilitate the biological functions of Trx.

PMID- 29469423
TI  - [Effect of excretory/secretory protein of Trichinella spiralis adult worm on CLP
      induced sepsis in mice].
AB  - OBJECTIVE: To observe the effect of excretory/secretory products from Trichinella
      spiralis adult worms (AES) on cecal ligation and puncture (CLP) -induced sepsis
      in mice. METHODS: Forty-eight BALB/c mice were randomly divided into 3 groups:a
      sham operation group (PBS + sham group, Group A), a CLP-induced sepsis group
      (PBS+CLP group, Group B) and an AES treatment group (AES+CLP group, Group C). The
      mice of each group were intraperitoneally injected with 25 MUg of AES or PBS only
      as a control in a total volume of 200 MUl. Eight mice from each group were
      selected randomly for survival analysis of 96 hours. The other 8 mice in each
      group were observed for pathological changes in the lung, liver and kidney
      tissues by HE staining 12 h after CLP, and then determined for the detection of
      cytokines including TNF-alpha, IL-1beta, IL-6, IL-10 and TGF-beta in the sera by
      ELISA. RESULTS: The difference among the survival rates of mice in the 3 groups
      was statistically significant (chi2 = 21.16, P < 0.05). Compared to Group A
      (100%), the survival rate of mice in Group B (0) decreased significantly (P <
      0.05), and also the pathological damage degrees in the lung, liver and kidney
      tissues of the mice in Group B increased significantly after CLP. Compared with
      the mice in group B, the survival rate of those in Group C (70%) increased
      significantly (P < 0.05), and the pathological damage degrees in the lung, liver
      and kidney tissues of the mice in Group C decreased significantly after the
      treatment with AES. The differences among the levels of pro-inflammatory
      cytokines TNF-alpha (F = 27.11, P < 0.05), IL1beta (F = 18.75, P < 0.05) and IL-6
      (F = 100.93, P < 0.05) in the sera of the mice in the three groups were
      statistically significant. Compared with the mice in Group A, the levels of the 3
      cytokines of those in Group B increased significantly (all P < 0.05). However,
      after the treatment with AES, the levels of the pro-inflammatory cytokines of
      those in Group C decreased significantly (all P < 0.05). The differences among
      the levels of immunoregulatory cytokines IL-10 (F = 10.88, P < 0.05) and TGF-beta
      (F = 11.37, P < 0.05) in the sera of the mice in the three groups were also
      statistically significant. Compared with the mice in Group B, the levels of IL-10
      and TGF-beta of those in Group C were higher after treatment with AES (both P <
      0.05). CONCLUSIONS: T. spiralis AES has a therapeutic potential for alleviating
      sepsis induced by CLP in mice.

PMID- 29469424
TI  - [Investigation on species and community ecology of Acaroid mites breeding in
      stored traditional Chinese animal medicinal materials].
AB  - OBJECTIVE: To investigate the species of Acaroid mites breeding in the stored
      traditional Chinese animal medicinal materials and the relationship between its
      community and habitats. METHODS: A total of 30 samples of traditional Chinese
      animal medicinal herbs were collected from Wuhu City, Anhui Province, China. The
      mites were isolated by the directly microscopic and floatation microscopic
      examinations, and then identified and counted under a light microscope. RESULTS:
      Acaroid mites was represented in 28 of the 30 samples, and the breeding rate
      accounted for as high as 93.3% (28/30). Totally, 13 species of Acaroid mites were
      identified, which belonged to 4 families and 9 genera. The densities of Acaroid
      mites were top in 6 Chinese herbal medicines, such as corium erinacei,
      aspongopus, hirudo, pheretima aspergillum, Apostichopus and huechys. The
      diversity parameters of these six traditional Chinese animal medicinal herbs were
      calculated. The highest richness indexes were in aspongopus and hirudo, the
      highest diversity index was in hirudo, and the highest evenness index was in
      Apostichopus. CONCLUSIONS: There are Acaroid mites breeding in parts of the
      traditional Chinese animal medicinal herbs stored in Wuhu. In the storage and
      processing of Chinese herbal medicines, we should pay attention to the prevention
      and control of mites.

PMID- 29469425
TI  - [Morphologic observation on Histiostoma feroniarum in Allium cepa].
AB  - OBJECTIVE: To observe the external morphology of Histiostoma feroniarum hypopus
      under a light microscope. METHODS: The samples were collected in a mushroom
      cultivation base, and the H. feroniarum hypopus was isolated and purified. The
      slide samples were prepared and observed under an optical microscope. RESULTS:
      The back body of the H. feroniarum hypopus was flat with tiny bristles, the
      epidermis was of significant ossification, the ventral had four pairs of slender
      feet stretched, the sucker plate was prosperous in the end of the body, and the
      sucker plate had eight suckers. The gnathosoma was thin, long and highly
      specialized. CONCLUSIONS: The light microscopy shows the morphological
      characteristics of H. feroniarum hypopus, providing the basis for identifying and
      life cycle study.

PMID- 29469426
TI  - [Tyrophagus palmarum and its hypopus found in feed of Tenebrio molitor].
AB  - OBJECTIVE: To observe the Tyrophagus palmarum and its hypopus in feed of Tenebrio
      molitor. METHODS: Feed samples were collected from T. molitor farms, and T.
      palmarum and its hypopus were separated from the samples by the vibration sieve
      method and floating method. The glass specimens were prepared and T. palmarum and
      its hypopus were observed under an optical microscope. RESULTS: Under the light
      microscope, the skin of T. palmarum was smooth and bright, the color of legs and
      chelicerae was relatively dark, the length of dorsal seta d2 was 3-4 times longer
      than d1 and la; The omega1 in tarsus of leg I, II was short rod, and its top was
      not tapered; the sucker plate in tarsus of leg IV located in the middle of the
      section. The hypopus was oblate, and there were two pairs of legs in front which
      extended to body. The rear end of hypopus became pointless and round, wrapping
      around a transparent and ossification skin. CONCLUSIONS: Light microscopy shows
      the morphological characteristics of T. palmarum and its dormant body, providing
      the basis for identifying the hypopus.

PMID- 29469427
TI  - [Establishment of a monitoring database of historical Oncomelania hupensis
      environments at grass - root level for schistosomiasis prevention based on Google
      Earth].
AB  - OBJECTIVE: To establish a monitoring database of historical Oncomelania hupensis
      environments at grass-root level for schistosomiasis prevention based on Google
      Earth (GE), so as to improve the management efficiency of historical O. hupensis
      environments. METHODS: GE was labeled with the information about the historical
      O. hupensis environments through adding landmark, path and polygon. Meanwhile,
      POCO web album was used to storage the practice situation pictures of the
      environments, which could be imported into GE so that the environments could be
      monitored dynamically. RESULTS: There were 553 historical O. hupensis snail
      environments in Yangjian Town, Xishan District, Wuxi City and the accumulative
      area was 506 000 m2. Among these environments, 224 (40.5%) were Class IV
      environments, accounting for 40.5% of accumulative area. CONCLUSIONS: The
      monitoring database of historical O. hupensis environments based on GE at country
      level is established successfully and it can be used to manage the historical
      snail environments visually and monitor the changes dynamically.

PMID- 29469428
TI  - [Effect of comprehensive schistosomiasis control in Changzhou City from 2004 to
      2014].
AB  - OBJECTIVE: To evaluate the effect of comprehensive schistosomiasis control in
      Changzhou City in recent 10 years, so as to provide the evidences for formulating
      the future prevention and control strategy. METHODS: The work reports and the
      data of the schistosomiasis comprehensive control projects in Changzhou City from
      2004 to 2014 were collected, the infection status of residents and livestock as
      well the Oncomelania hupensis snail situation were analyzed, and the
      implementation effect of the comprehensive control projects was evaluated.
      RESULTS: From 2004 to 2014, totally 215 368 person-times were examined, and the
      positive rate of the blood examinations of the population was 0.24% (478/198
      356), and there were no positive cases detected out by using the miracidium
      hatching method. Totally 11 935 domestic animals were detected and no positives
      were found. From 2004 to 2014, the total area with snails was 92.27 hm2, and
      marshland, inland and mountain environments accounted for 34.75%, 34.82% and
      30.43%, respectively. The newly discovered area with snails was 34.40 hm2, and
      marshland, inland and mountain environments accounted for 2.62%, 71.22% and
      26.16%, respectively. Totally 8 511 snails were dissected and no schistosome
      infected snails were found. From 2004 to 2014, a total of 242 600 harmless
      toilets were built, 2 704 700 domestic animals were reared in pens, 5.82 km-long
      rivers were dredged, 2 250.11 hm2 of protective forests were constructed, a total
      area of 625.79 hm2 were controlled with molluscicides, and an area of 149.58 hm2
      were environmentally transformed. Totally 5.4 million people received health
      education. The awareness rate of knowledge on schistosomiasis control of
      residents was 96.00% in 2014. CONCLUSIONS: There exists the risks of snails
      import and diffusion and schistosomiasis resurrection in Changzhou City, but
      under the condition of continuous implementation of comprehensive control
      measures, the endemic situation of schistosomiasis is stable and the control
      achievement is consolidated in this city.

PMID- 29469429
TI  - [Oncomelania hupensis snail control effects of molluscicides with different
      formulations in field in marshland and lake regions].
AB  - OBJECTIVE: To observe the Oncomelania hupensis snail control effects of
      molluscicides with different formulations in the ditch with unstable water level
      in field of marshland and lake areas, so as to provide the evidence for
      formulating the prevention strategies. METHODS: A drainage channel with O.
      hupensis snails in Jiangling County, Jingzhou City were selected as the study
      field, then it was divided into 6 segments, except 1 segment was treated as the
      blank control group for observing the natural mortality rate of the snails, the
      other 5 segments were treated as observation groups, where 4% niclosamide
      ethanolamine salt powder, 5% niclosamide ethanolamine salt granule, 25%
      suspension concentrate of niclosamide ethanolamine salt, 26% suspension
      concentrate of metaldehyde and niclosamide ethanolamine salt, 50% niclosamide
      ethanolamine salt wettable powder were applied respectively. Before and after the
      mollusciciding, the snail surveys were carried out through the systematic
      sampling method, and the short- and long-term effects of snail control were
      observed, and the mortality rates of the snails on the slope above the water
      level and those below the water level were compared. RESULTS: When 7 d and 15 d
      after mullusciciding, the mortality rates of snails on the slope above the water
      level in each observation group were 79.52%-97.87% and 90.43%-96.30%,
      respectively, when compared with those before mollusciciding, all the differences
      were statistically significant (all P < 0.01). When 7 d after mullusciciding, the
      mortality rates of snails below the water level in each observation group were
      17.11%-50.00%, which were all lower than those of the snails on the slope above
      the water level in the corresponding groups (all P < 0.05); when 15 d after
      mullusciciding, the rates were 9.43%-95.24%, and those in 25% suspension
      concentrate of niclosamide ethanolamine salt, 26% suspension concentrate of
      metaldehyde and niclosamide ethanolamine salt, 50% niclosamide ethanolamine salt
      wettable powder groups were all lower than those of the snails on the slope above
      the water level in the corresponding groups (all P < 0.01). Compared with the
      densities of living snails before mollusciciding, those 6 months after
      mollusciciding in each observation group decreased by 70.21%-78.98%. CONCLUSIONS:
      The molluscicides in the formulation of powders and granule are suitable for both
      the snail environment with or without water, while those in the formulation of
      suspension agents and wettable powders are suitable only for environments with
      water.

PMID- 29469430
TI  - [Application of solution focused approach in nursing of patients with advanced
      schistosomiasis].
AB  - OBJECTIVE: To investigate the effect of nursing with solution focused approach in
      advanced schistosomiasis patients. METHODS: Fifty three patients with advanced
      schistosomiasis in the Liujiahu Hospital for Schistosomiasis Control of Yiyang
      City were randomized selected and separated into an intervention group and a
      control group. The patients of the intervention group received the conventional
      nursing plus solution focused approach, while the patients of the control group
      received only the conventional nursing. The effectiveness of nursing and
      treatment was evaluated in the two groups comparatively. RESULTS: The knowledge
      of self-care skills, medical compliance behaviors and services satisfaction
      degree in the intervention group were higher than those in the control group
      (chi2 = 3.78, 2.87, 4.09 respectively, all P < 0.05). The occurrence rate of
      upper gastrointestinal bleeding in the intervention group was significantly lower
      than that in the control group (chi2 = 4.894, P < 0.05). The average
      hospitalization duration of the intervention group was shorter than that of the
      control group (t = 4.17, P < 0.05). CONCLUSIONS: The solution focused approach is
      a feasible and effective method in course of nursing of advanced schistosomiasis
      patients. It enhances the confidence of the patients and the trustiness of the
      patients to the health care providers. The complications and the hospitalization
      duration of the patients are reduced.

PMID- 29469431
TI  - [Application of clinical nursing path integrated with holistic nursing in
      advanced schistosomiasis patients with ascites].
AB  - OBJECTIVE: To evaluate the effect of the clinical nursing path integrated with
      the holistic nursing on advanced schistosomiasis patients with ascites. METHODS:
      A total of 226 advanced schistosomiasis patients with ascites were randomly
      divided into a control group and an experimental group (113 cases each group).
      The subjects in the experimental group were nursed by the clinical nursing path
      integrated with the holistic nursing, while those in the control group were
      nursed only by the holistic nursing. Then the clinical relevant indexes of the
      two groups were observed, and the quality of life of the patients before and
      after hospital discharge was assessed. RESULTS: The improvement rate,
      satisfaction degree, and awareness rate of health knowledge of the patients in
      the experiment group were 93.8%, 100% and 97.4%, respectively, which were
      significantly higher than those of the control group (all P < 0.05). The
      mortality rate and the complication rate of the patients in the experimental
      group were 0 and 2.7%, respectively, which were significantly lower than those of
      the control group (both P < 0.05). In addition, the average hospitalization days
      and the hospitalization cost of the experiment group were (12.2 +/- 0.7) d and (4
      725.0 +/- 310.1) Yuan respectively, which were less than those of the control
      group (both P < 0.01). When 6 months after the discharge from hospital, the
      quality of life of the patients in the experimental group in various fields was
      significantly better than that of the control group (all P < 0.05). CONCLUSIONS:
      The clinical nursing pathway integrated with holistic nursing can effectively
      improve the improvement rate and decrease the mortality of the advanced
      schistosomiasis patients with ascites; meanwhile, it can shorten the
      hospitalization time and save the hospitalization cost. Therefore, this nursing
      model is suitable for popularization and application in the treatment and nursing
      work of the advanced schistosomiasis assistance.

PMID- 29469432
TI  - [Investigation of tick bites in outpatients with fever from health care
      facilities in Tengchong County].
AB  - OBJECTIVE: To study the prevalence of tick bites and relative factors of
      outpatients with fever from health care facilities in Tengchong County. METHODS:
      From July to August, 2014, the outpatients with fever in five health care
      facilities namely Tengchong Center for Disease Control and Prevention, Hehua
      Health Center, Jietou Health Center, Qushi Health Center and Xinhua Health Center
      were investigated by questionnaires. The factors related to tick bites were
      explored with the univariate analysis and multiple regression models. RESULTS:
      Totally 884 effect questionnaires were acquired. Among the 884 participants, 85
      (9.6%) had experienced tick bites. The frequency of tick bites was associated
      with locations, gender, age group, ownership of cattle, working at foreign
      country, firewood cutting and lumbering in the forest (all P < 0.05). The
      multiple regression revealed that the male and people raising cattle, working at
      foreign country, engaging in firewood cutting and lumbering in the forest had a
      more risk for tick bites. CONCLUSIONS: Tick bites are common in the residents of
      Tengchong County. The risk of being bitten varies in different populations. The
      local health departments should promote health education in the high-risk
      population to reduce the risk of infecting tick-borne diseases.

PMID- 29469433
TI  - [Evaluation of integrated strategy in prevention and control of intestinal
      nematodiasis in Hongze County, Jiangsu Province].
AB  - OBJECTIVE: To evaluate the effect of the integrated strategy in prevention and
      control of intestinal nematodiasis in Hongze County, so as to provide the
      evidence for formulating the control strategies and measures in the future.
      METHODS: Since 1995, the integrated strategy has been carried out for intestinal
      nematodiasis, and the measures included deworming, health education, safe water,
      sanitation and environmental remediation. The effects of the integrated strategy
      were evaluated by the investigations of the prevalence of soil-transmitted
      nematodiasis, awareness of health knowledge and behaviors of residents. RESULTS:
      From 1995 to 2014, 601 900 person-times were administrated with deworming
      medication and the coverage rate of villages and towns was 100%. The benefit rate
      of safe water was 100%. The popularity rate of harmless toilets was 92.77%. The
      prevalence of intestinal nematodiasis decreased from 26.04% in 1995 to 0.56% in
      2014, and the difference had statistical significance (chi2 = 693.54, P < 0.01).
      The awareness rate of health knowledge and correct rate of health behaviors
      increased from 43.13% and 40.94% in 1995 to 98.00% and 96.80% in 2012,
      respectively (chi2 = 181.97 and 182.14 respectively, P<0.01). CONCLUSIONS: The
      prevalence of intestinal nematodiasis has been controlled effectively through the
      integrated strategy in Hongze County, Jiangsu Province.

PMID- 29469434
TI  - [Analysis of projects of infectious disease epidemiology sponsored by National
      Natural Science Foundation of China].
AB  - OBJECTIVE: To analyze the projects on the infectious disease epidemiology
      sponsored by the National Natural Science Foundation of China (NSFC), explore the
      hotspot and development trend, and offer a reference for researchers in this
      field. METHODS: Based on the NSFC database, the projects on the infectious
      disease epidemiology (H2609) sponsored from 1987 to 2014 were analyzed. The
      changes of fund numbers, amounts and research fields were described. RESULTS:
      During the study period, NSFC sponsored 373 projects, including 228 general
      projects (61.1%), 78 youth projects (20.9%) and 67 other projects (18.0%). The
      average amount of the grant was 358.2 thousand Yuan (20 thousand-8 million). The
      main sponsored research fields were mechanisms of pathogen and immunity (36.2%)
      and population-based epidemiological studies (33.0%). The top three diseases were
      hepatitis, HIV/AIDS and tuberculosis. CONCLUSIONS: The amount of funding on
      researches of infectious disease epidemiology has increased continuously, which
      has played an important role in training scientific talents in the field of
      prevention and control of infectious diseases.

PMID- 29469435
TI  - [Preliminary exploration of mobile terminal data acquisition in malaria control].
AB  - OBJECTIVE: To develop a mobile terminal data acquisition for data collection of
      malaria prevention and control in the field. METHODS: Based on 3G, Bluetooth, GPS
      and/or Bei Dou Navigation Satellite System (BDS) and wireless network
      communication technology (WIFI), a mobile terminal data acquisition for data
      collection of malaria prevention and control was developed. RESULTS: The
      developed system included 2 functional modules:a terminal and iCloud, and had
      examination, modification and deletion functions of malaria epidemiological data.
      By using GPS and GIS, the target population or institution could be accurately
      positioned to determine whether the distribution of malaria cases had a spatial
      aggregation. CONCLUSIONS: A mobile terminal data acquisition in malaria
      prevention and control is successfully developed, which is very convenient for
      data collection and submission of malaria prevention and control.

PMID- 29469436
TI  - [Schistosomiasis control effect of agricultural integrated development in Tieban
      Marshland of Yangtze River].
AB  - OBJECTIVE: To evaluate the schistosomiasis control effect of the comprehensive
      measures that focused on beachland smoothing and tillage cultivation in Tieban
      Marshland, Wuhan Section of the Yangtze River. METHODS: From 2011 to 2015, before
      and after the comprehensive control, the Oncomelania hupensis snail situations in
      Tieban Marshland were investigated in spring annually, and the residents aged 6
      65 years in Huayuan Community which was next to the marshland were examined to
      understand their schistosome infection status. In late July, 2014, the sentinel
      mouse surveillance was carried out. Moreover, the economic effectiveness of
      comprehensive development was evaluated. RESULTS: The schistosome infection rates
      of residents in 2011 (before the comprehensive control), 2012 (after the
      comprehensive control), and 2013 were 0.72% (3/414), 0.37% (2/536) and 0.31%
      (1/326), respectively, and no schistosomiasis patients were found in 2014 and
      2015. The snail area, the occurrence rate of frames with snails, and the average
      density of living snails in Tieban Marshland in 2005 decreased by 22.18%, 97.83%
      and 98.25%, respectively compared to those in 2011, and no schistosome infected
      snails were found. No positive mice were found in the sentinel mouse
      surveillance. The annual net income of Tieban Marshland increased by 233.33%
      compared to that before the comprehensive development. CONCLUSIONS: The endemic
      situation of schistosomiasis and snail situation declined significantly after the
      comprehensive development in Tieban Marshland, and the economic and social
      benefits are significant.

PMID- 29469437
TI  - [Prevalence and awareness of Toxoplasma gondii of pregnant women in Bazhou City,
      Hebei Province].
AB  - OBJECTIVE: To understand the prevalence and awareness of Toxoplasma gondii of the
      pregnant women in Bazhou City, Hebei Province, so as to provide the evidence for
      formulating effective prevention and control interventions. METHODS: The pregnant
      women with prenatal screening in the Fourth People's Hospital in Langfang City
      were selected and investigated with questionnaires. A part of the pregnant women
      were randomly sampled and received the ELISA test of the antibodies against T.
      gondii. RESULTS: Totally 672 pregnant women accepted the questionnaire survey,
      with an awareness rate of 19.49% (131/ 672). Totally 526 pregnant women of them
      were randomly selected to take the ELISA test, with a positive rate of 13.88%
      (73/ 526). The awareness rate and infection rate of T. gondii were related to the
      education level, occupation and place of residence (chi2= 5.89-17.62, all P <
      0.05), and the infection rate was negatively related to the awareness rate (chi2
      = 5.37, P < 0.05). CONCLUSIONS: Increasing the awareness rate of toxoplasmosis
      knowledge is one of the effective methods to control the disease. Therefore, the
      health education about T. gondii should be carried out actively.

PMID- 29469438
TI  - [Clinical analysis of 15 patients suffered from advanced ascetic schistosomiasis
      with tuberculous pleurisy].
AB  - OBJECTIVE: To discuss the clinical characteristics of advanced schistosomiasis
      combined with tuberculous pleurisy, so as to reduce misdiagnosis and
      mistreatment. METHODS: The clinical data of 15 patients suffered from advanced
      schistosomiasis combined with tuberculous pleurisy were collected and analyzed
      retrospectively. RESULTS: The 15 patients all showed various degrees of
      gastrointestinal symptoms with the performance of abdominal distension, digestive
      function and fatigue, 14 patients showed various degrees of edematous, 9 patients
      showed stuffiness, 4 patients had cough and expectoration, and 2 patients had low
      fever and night sweats. Three cases were diagnosed within 2 days after admission,
      9 cases were diagnosed within one week after admission, and 3 cases were
      diagnosed after one week. Fifteen patients all received anti-tuberculosis
      treatment based on routine liver protection, diuresis, and symptomatic and
      supportive treatment. One patient with severe liver and kidney dysfunction died
      and one with gastrointestinal bleeding died. The remaining 13 patients were
      clinically cured. CONCLUSIONS: The patients suffered from advanced
      schistosomiasis combined with tuberculous pleurisy do not show obvious
      tuberculosis poisoning symptoms, and are easily misdiagnosed and missed
      diagnosed. Therefore, physicians should pay much attention to the patients whose
      pleural effusion cannot subside effectively or whose symptom cannot improve.

PMID- 29469439
TI  - [Advances in researches of balantidiosis].
AB  - Balantidiosis is a disease infected with Balantidium coli, and swine is the main
      infection source. The infection of B. coli may cause diarrhea, extra intestinal
      infection and co-infection with other pathogens and even intestinal necrosis.
      Strengthening the manure management of both human and livestock, paying attention
      to personal hygiene and labor protection, and timely treatment of the patients
      are the main measures to control balantidiosis.

PMID- 29469440
TI  - [Analysis of endemic status of schistosomiasis in Gaoyou City from 1970 to 2009].
AB  - OBJECTIVE: To explore the changing rule of schistosomiasis endemic situation in
      Gaoyou City, so as to provide the evidences for schistosomiasis control in lake
      and marshland regions. METHODS: The endemic data of schistosomiasis of Gaoyou
      City from 1970 to 2009 were collected to analyze the endemic patterns of
      schistosomiasis in different control stages comprehensively. RESULTS: In the
      first years of infection control stage (1970-1975), transmission control stage
      (1976-1994) and transmission interruption stage (1995-2009), the prevalence rates
      of schistosomiasis were 4.20%, 0.80% and 0 in human and 3.00%, 0.51% and 0 in
      cattle respectively. In 1984, the positive rate of crowd stool tests fell to
      0.04%, which was reduced by 99.05% compared with that in 1970. From 1970 to 1980,
      the positive rates of stool tests of people and livestock were positively
      correlated significantly (r = 0.67, P < 0.05). After 1985, no local infection
      patients or cattle were found. No schistosome infected Oncomelania hupensis
      snails were found from 1970 to 2009. CONCLUSIONS: The comprehensive control
      measures have been insisted in Gaoyou City in different prevention and control
      stages. Although the snail situation is undulate, the prevalence of
      schistosomiasis steadily declines and the interruption of transmission has
      achieved.

PMID- 29469441
TI  - [Endemic status of schistosomiasis in People's Republic of China in 2016].
AB  - This report presents the endemic status of schistosomiasis in the People's
      Republic of China at national level in 2016, and analyzes the data collected from
      the national schistosomiasis prevention and control system and 454 national
      schistosomiasis surveillance sites. Among the 12 provinces (municipality and
      autonomous region) of endemic of schistosomiasis japonica in P. R. China, 5
      provinces (municipality and autonomous region), i.e., Shanghai, Zhejiang, Fujian,
      Guangdong and Guangxi, had achieved elimination, and 7 provinces of Sichuan,
      Yunnan, Jiangsu, Hubei, Anhui, Jiangxi and Hunan had achieved transmission
      control by the end of 2016. There are 451 endemic counties (cities, districts)
      covering 257 million people, specifically including 29 692 endemic villages of
      69.39 million people at risk. Among the 451 endemic counties (cities, districts),
      35.25 % (159/451), 42.35% (191/451) and 22.39% (101/451) reached the criteria of
      elimination, transmission interruption and transmission control, respectively in
      2016. By the end of 2016, it was estimated of 54 454 infections of schistosome,
      decreased by 29.46% compared with 77 194 in 2015. No acute schistosomiasis case
      was reported in 2016. There were 30 573 advanced schistosomiasis cases documented
      in 2016. A total of 8 500 710 individuals received schistosomiasis examinations
      and 600 individuals were parasitologically diagnosed, decreased by 83.36%
      compared with 3 606 in 2015. The Oncomelania hupensis snail survey was performed
      in 22 140 endemic villages and O. hupensis snails were found in 7 106 villages,
      accounting for 32.109% of the total villages, with 20 newly detected villages
      with snails. The snail survey covered area of 813 963.91 hm2 and snails were
      found in an area of 235 096.04 hm2, including a newly detected area of 1 346.48
      hm2. No schistosome-infected snails were found in 2016. A total of 881 050
      bovines were raised in the schistosomiasis endemic area. Of them, 510 468 bovines
      received examinations, resulting in 8 schistosome-infected bovines. There were
      147 642 schistosomiasis cases receiving drug treatment in 2016, with 2 303 555
      individuals undergoing expanded chemotherapy; there were 9 bovines with
      schistosomiasis receiving drug treatment, with 439 857 bovines undergoing
      expanded chemotherapy; a total of 139 483.84 hm2 area with snail control by using
      molluscicides, with actual molluscicide-treated area of 73 941.75 hm2; and 3
      101.52 hm2 snail habitants were treated by environmental modification. Based on
      the data from the 454 national schistosomiasis surveillance sites, the mean
      Schistosoma japonicum infection rate was 0.02% and 0.0078% in humans and bovines,
      respectively. No schistosome-infected snails were found in all the surveillance
      sites. The results demonstrate a decline in the endemicity of schistosomiasis in
      P. R. China compared with the level of 2015. However, the distribution area of
      snails in China is still large and the infection source of schistosomiasis still
      exists to some extent in some endemic areas; in some regions, the task to reach
      the standard of transmission interruption is still arduous. There are still
      objective factors of epidemic and transmission and risk factors of endemic
      reversal and rebound for schistosomiasis. So, further control and effective
      surveillance as well as accurate prevention and control should be implemented to
      promote the elimination process on schistosomiasis in P. R. China.

PMID- 29469442
TI  - [Studies on resistance of Schistosoma to praziquantel XVI Biological
      characteristics of praziquantel-resistant isolates of Schistomoma japonicum in
      Oncomelania hupensis snails].
AB  - OBJECTIVE: To investigate the difference of biological characteristics between
      the praziquantel-resistant and -susceptible isolates of Schistosoma japonicum in
      intermediate host Oncomelania hupensis snails. METHODS: Mice were infected with
      cercariae of praziquantel-resistant and -susceptible isolates of S. japonicum,
      and the parasite eggs were collected 37 days post-infection to hatch miracidium.
      Then, the snails were infected with the miracidium of each parasite isolate. The
      snail infection, survival rate of infected snails, prepatent period of cercariae,
      and the total number of cercariae shed from each infected snail were observed and
      compared between the praziquantel-resistant and -susceptible isolates of S.
      japonicum. RESULTS: If each snail was exposed to a single miracidium, there were
      significant differences between the praziquantel-resistant and -susceptible
      Jiangsu isolates in the snail infection (8.99% vs. 19.74%; chi2 = 3.948, P =
      0.047) and the number of cercaria released from a single snail (1 460.2 vs. 1
      039.3; t = 2.507, P = 0.02), and there were significant differences between the
      praziquantel-susceptible and -resistant Hunan isolates in the snail infection
      (10.00% vs. 21.52%; chi2 = 3.980, P = 0.046) and the number of cercaria released
      from a single snail (1 319.4 vs. 1 003.5; t = 2.566, P = 0.017). However, there
      were no significant differences between the praziquantel-resistant and 
      susceptible isolates of S. japonicum in the prepatent period of cercariae and the
      survival rate of infected snails (P > 0.05). CONCLUSIONS: The praziquantel
      resistant isolate of S. japonicum has a higher susceptibility to O. hupensis but
      less cercaria released from each infected snail than the susceptible isolate.

PMID- 29469443
TI  - [Studies on resistance of Schistosoma to praziquantel XVII Biological
      characteristics of praziquantel-resistant isolates of Schistosoma japonicum in
      mice].
AB  - OBJECTIVE: To investigate the biological characteristics of the praziquantel
      resistant isolate of Schistosoma japonicum in mice, so as to explore the
      pathogenicity to definitive hosts and transmission intensity of the praziquantel
      resistant isolate of S. japonicum. METHODS: Mice were infected with the cercariae
      released from two praziquantel-resistant isolates and two praziquantel
      susceptible isolates of S. japonicum. The mouse-Oncomelania hupensis snail-mouse
      cycle was established and maintained in the laboratory. The prepatent period of
      parasite eggs, egg production, egg distribution in mice, parasite susceptibility
      to mice and egg size were investigated in each parasite isolate. RESULTS: The
      prepatent period of parasite eggs, egg counts in mouse feces, adult worms
      recovered from each mouse, egg counts in mouse tissues, egg counts in the mouse
      liver, and egg counts in intestine tissues were 36.1 d and 36.8 d (t = 0.907, P =
      0.372), 14.6 / 100 mg and 21.2 / 100 mg (t = 2.946, P = 0.007), 20.5 and 25.1
      worms per mouse (t = 2.128, P = 0.042), 31 303 and 38 594 per paired adult worm
      (t = 2.185, P = 0.04), 14 810 and 19 715 per paired adult worm (t = 2.934, P =
      0.007), and 16 493 and 18 879 per paired adult worm (t = 1.044, P = 0.309) in the
      mice infected with Jiangsu praziquantel-susceptible and -resistant isolates of S.
      japonicum, respectively, and there were no significant differences between
      Jiangsu praziquantel-susceptible and -resistant isolates of S. japonicum in the
      length of paired adult worms (t = 0.328, P = 0.744), female adult worms (t =
      0.386, P = 0.701) or male adult worms (t = 0.332, P = 0.741). The prepatent
      period of parasite eggs, egg counts in mouse feces, adult worms recovered from
      each mouse, egg counts in mouse tissues, egg counts in the mouse liver, and egg
      counts in intestine tissues were 35.5 d and 35.6 d (t = 0.169, P = 0.867),
      13.3/100 mg and 18.9/100 mg (t = 3.622, P = 0.001), 17.6 and 25.1 worms per mouse
      (t = 3.153, P = 0.004), 30 932 and 53 903 per paired adult worm (t = 3.865, P =
      0.001), 12 307 and 26 363 per paired adult worm (t = 4.388, P < 0.01), and 18 625
      and 27 541 per paired adult worm (t = 2.679, P = 0.012) in the mice infected with
      Hunan praziquantel-susceptible and -resistant isolates of S. japonicum,
      respectively, and there were no significant differences between Hunan
      praziquantel - susceptible and - resistant isolates of S. japonicum in the length
      of paired adult worms (t = 0.853, P = 0.397), female adult worms (t = 0.573, P =
      0.569) or male adult worms (t = 0.742, P = 0.461). CONCLUSIONS: The praziquantel
      resistant isolate of S. japonicum has a higher parasite egg production and more
      eggs deposited in the mouse liver than drug-susceptible isolate, suggesting that
      the praziquantel-resistant isolate of S. japonicum exhibits a greater
      pathogenicity to definitive hosts. In addition, more parasite eggs are detected
      in the feces of mice infected with the praziquantel-resistant isolate of S.
      japonicum relative to the drug-susceptible isolate, indicating that the
      praziquantel-resistant isolate of S. japonicum exhibits a greater
      transmissibility than the drug-susceptible isolate.

PMID- 29469444
TI  - [Role of new strategy in transmission control of schistosomiasis in Poyang Lake
      region].
AB  - OBJECTIVE: To evaluate the role of new strategy in the transmission control of
      schistosomiasis in Poyang Lake region. METHODS: The information and epidemic data
      of schistosomiasis control were collected and analyzed in Poyang Lake region from
      2005 to 2016. RESULTS: After eleven years of carrying out the new strategy,
      thirteen counties achieved the objective of transmission control in Poyang Lake
      region. In 2016, the number of schistosomiasis cases and human infection rate
      were 10 301 and 0.03%, decreased by 89.64% and 99.45% compared with those in
      2005, respectively. The number of cattle and schistosome -infected cattle were 68
      152 and 5, decreased by 50.84% and 99.83% compared with those in 2005,
      respectively. The average density of Oncomelania hupensis snails was decreased by
      61.52%. No schistosome-infected snails were found since 2014. CONCLUSIONS: The
      new strategy accurately locates the key points and targets of schistosomiasis
      transmission chain, which has controlled the human and animal's fecal eggs from
      polluting grassland, and cut off the transmission chain, reduced both the
      infection rates of human and animal and the re-infection risk, and promoted to
      achieve the target of schistosomiasis transmission control in Poyang Lake region.

PMID- 29469445
TI  - [Effect of water conservancy schistosomiasis control projects combined with
      molluscicide to control Oncomelania hupensis snails in rivers connecting with
      Yangtze River in Pukou District, Nanjing City].
AB  - OBJECTIVE: To evaluate the effect of the water conservancy schistosomiasis
      control projects combined with molluscicide to control Oncomelania hupensis
      snails in the rivers connecting with the Yangtze River. METHODS: The water
      conservancy schistosomiasis control projects of Zhujiashan River, Qili River and
      Gaowang River were chosen as the study objects in Pukou District, Nanjing City.
      The data review method and field investigation were used to evaluate the effect
      of the water conservancy schistosomiasis control projects combined with
      molluscicide to control O. hupensis snails. RESULTS: After the projects of the
      water level control and concrete slope protection and mollusciciding were
      implemented, the snails in the project river sections were completely eliminated.
      The snail diffusion did not happen in the inland irrigation area too. In the
      outside of the river beach, though the snails still existed, the snail densities
      plunged below 1.0 snail per 1.0 m2. CONCLUSIONS: The comprehensive measures of
      the combination of water level control, concrete slope protection and
      mollusciciding can effectively control and eliminate the snails, and prevent the
      snails from spreading.

PMID- 29469446
TI  - [Risk analysis of imported schistosomiasis in Shanghai City from 2005 to 2015].
AB  - OBJECTIVE: To understand the risk situation of imported schistosomiasis and its
      main influencing factors in Shanghai City from 2005 to 2015. METHODS: A
      retrospective survey was performed, and the database was established based on the
      data collection of imported schistosomiasis, Oncomelania hupensis snail situation
      and mobile population in Shanghai City from 2005 to 2015. RESULTS: From 2005 to
      2015, the mobile population in Shanghai City increased by 123.92%, which reached
      about 9 816 500, and 54.70% of them were located in the inner suburban districts.
      The accumulated areas with snails of 7.13 hm2 were found in 16 towns of 4 outer
      suburbs (excluding Chongming District). A total of 23 cases of imported
      schistosomiasis were found in Shanghai City, and the number of the imported
      schistosomiasis cases was on the downward trend (rs = -0.782, P = 0.004). From
      2005 to 2009, 11 out of 13 imported schistosomiasis cases (84.62%) were
      distributed in the inner suburban districts where no O. hupensis snails were
      found at the same time. From 2010 to 2015, 9 out of 10 imported schistosomiasis
      cases (90%) were distributed in the outer suburban districts where O. hupensis
      snails were found at the same time. CONCLUSIONS: The number of imported
      schistosomiasis cases in Shanghai is on the downward trend. However, the threat
      of imported schistosomiasis to the prevention and control of schistosomiasis in
      Shanghai City should not be ignored.

PMID- 29469447
TI  - [Epidemiological characteristics of imported malaria and influencing factors of
      severe cases in Anhui Province].
AB  - OBJECTIVE: To analyze the epidemiological characteristics of imported malaria
      cases and investigate the influencing factors of severe cases in Anhui Province,
      so as to provide the evidence for improving the control strategy. METHODS: The
      epidemiological data of imported malaria cases in Anhui Province from January
      1st, 2012 to April 18th, 2017 were collected and analyzed. RESULTS: The imported
      malaria cases in Anhui Province were mainly young men of migrant workers. There
      were imported malaria cases in 79% (83/105) of counties (districts) in Anhui
      Province.. Totally 686 imported malaria cases were recorded, in which there were
      62 severe cases (9.04%), and four death cases with the mortality rate of 0.58%.
      The age, education, initial diagnosed departments, initial diagnosed results,
      time from onset to seeing a doctor, and time from seeing a doctor to diagnosis
      were the influencing factors for the severe cases. CONCLUSIONS: The proportion of
      severe imported malaria cases is high in Anhui Province. The monitoring
      sensitivity, clinician's awareness of malaria diagnosis, and health education for
      migrant workers should be improved.

PMID- 29469448
TI  - [Trends of soil-transmitted nematode infections in Jiangxi Province].
AB  - OBJECTIVE: To analyze the status and trends of soil-transmitted nematode
      infections in Jiangxi Province from 1989 to 2014, so as to provide the evidence
      for generating the strategy of soil-transmitted nematode prevention and control.
      METHODS: The data of three epidemiological surveys on human parasitic diseases
      (in 1989, 2002 and 2014) were classified and analyzed. The stool examination by
      Kato-Katz's thick smear method was adopted for the investigation of soil
      transmitted nematode infections. RESULTS: The total infection rate of soil
      transmitted nematodes decreased by 91.89% from 77.67% in 1989 to 6.30% in 2014,
      in which the infection rate of Ascaris lumbricoides decreased by 98.78% from
      71.11% to 0.87%, the infection rate of Trichuris trichiura decreased by 96.80%
      from 29.67% to 0.95%, and the infection rate of hookworm declined by 73.57% from
      17.63% to 4.66%. The infection rates of soil-transmitted nematodes in the female
      were higher than those in the male in three surveys. In different ecological
      districts, the infection rates of soil-transmitted nematodes in the female were
      also higher than those in the male, except in Zhe-Min Ecological District in 2002
      and 2014. A declined trend of the infection was showed in all age-groups in the
      three surveys, but it slowed down by the growth of age, i.e., the reduction rate
      was 97.03% in the age group of < 10 years while 80.62% in the age group of >70
      years. In 2014, the number of persons infected with soil-transmitted nematodes
      occupied 65.4% of the whole number of persons infected with intestinal parasites.
      CONCLUSIONS: The mean infection rates of soil-transmitted nematodes decrease
      obviously in human population in different ecological districts, but the soil
      transmitted nematodes are still the main species in intestinal parasite
      infections. The sequence of dominant species changes from A. lumbricoides,
      hookworm and T. trichiura in 1989 to hookworm, T. trichiura and A. lumbricoides
      in 2014. The rural female and elder people are the key population, while hookworm
      is the key species for the prevention and control of soil-transmitted nematodes.

PMID- 29469449
TI  - [Investigation on sanitation of freshwater aquaculture environments and
      Clonorchis sinensis intermediate host infection in a city of Pearl River Delta
      region, China].
AB  - OBJECTIVE: To understand the current status of the sanitation of freshwater
      aquaculture environments, and Clonorchis sinensis infection of freshwater fish in
      the aquaculture and market in a city of Pearl River Delta region, so as to
      provide the evidence for formulating the prevention and control strategy of
      clonorchiasis sinensis. METHODS: In 2016, based on the distribution of freshwater
      aquaculture, 36 freshwater fish ponds among 14 towns were selected for sampling
      and investigation, and 10-20 pieces were collected from each pond. Besides, 3
      aquatic product wholesale markets were included, among which 3-6 stalls were
      selected from each market, and 20-30 pieces were collected from each stall. The
      metacercaria in the fish was examined by the digestion method. RESULTS: In the 36
      fish ponds, there were no toilets with the stool being drained into fish ponds
      directly, and there was only one pond with duck sheds with the stool being
      drained into fish ponds directly. Totally 437 pieces of freshwater fish from
      ponds were detected, with a metacercaria positive rate of 4.35% (19/437). The
      metacercaria positive fish were distributed in 50% (7/14) of towns and 25% (9/36)
      ponds. The positive rates of crucian carp, grass carp, dace, aristichthysnobilis,
      and tilapia were 13.95% (6/43), 4.76% (9/189), 4.44 (2/45), 1.55% (2/129), and 0
      (0/31) respectively, with statistically significant difference (chi2 = 13.46, P =
      0.01). Totally 307 pieces of freshwater fish were collected from the wholesale
      markets, with a total positive rate of 1.95% (6/307). The positive rate of grass
      carp and aristichthysnobilis were 3.20% (4/125) and 2.78% (2/72) respectively,
      and no positive samples were found in crucian carp, dace and tilapia, with no
      statistically significant difference among the different fish in the infection
      rate (Fisher exact P = 0.75). CONCLUSIONS: The sanitation of freshwater
      aquaculture environments in a city of Pearl River Delta region is relative good.
      However, there are different degrees of Clonorchis sinensis infection of
      freshwater fish in some aquaculture environments and markets.

PMID- 29469450
TI  - [Population structure and seasonal dynamics of mosquitoes in different types of
      residential areas].
AB  - OBJECTIVE: To investigate the effect of the type of neighborhoods on the
      population structure and dynamics of mosquitoes. METHODS: The adult population
      dynamics and larvae breeding of mosquitoes in four different types of
      neighborhoods were investigated in Yangzhou City. RESULTS: The number of trapped
      mosquitoes was the largest in the urban villages, and more than 800 adult
      mosquitoes were trapped in each urban village, which was significantly higher
      than that of ordinary and high quality residences. Aedes albopictus and Culex
      pipiens pallens were dominant species (D > 10%) in the four types of residential
      areas, and Ae. albopictus was the most dominant species (D > 57%). The peak
      occurrence of Ae. albopictus in different areas occurred in early June, and it
      occurred again in the urban village in the middle of September. The occurrence
      quantity of Cx. pipiens pallens was stable in the ordinary residence and high
      quality residence, while in the urban village and resettlement residential area,
      the peak occurred in mid-October. The orders of positive rates, densities and the
      numbers of mosquitoes in the different types of residential areas were:the urban
      villages> the resettlement residence> the ordinary residence> the high quality
      residence. The water vat had the highest positive rate in all kinds of larval
      habitats, followed by tires and green belt with garbage water. CONCLUSIONS: The
      main mosquito species in the four different types of residential areas are all
      Ae. albopictus and Cx. pipiens pallens, but the positive rate, density and the
      number of mosquitoes in the different types significantly change, especially in
      the urban villages, the number and the occurrence peak are significant different
      from those in the other types of residential areas.

PMID- 29469451
TI  - [Epidemiological characteristics of malaria prevalence in Danyang City from 2004
      to 2015].
AB  - OBJECTIVE: To analyze the epidemiological characteristics of malaria prevalence
      in Danyang City from 2004 to 2015, so as to provide the evidence for formulating
      the strategy of prevention and control of malaria. METHODS: The data of malaria
      serum tests, the reported malaria cases from the Internet Reporting System, and
      the epidemiological case survey from 2004 to 2015 as well as the mosquito
      monitoring data from 2008 to 2015 were collected and analyzed. RESULTS: From 2004
      to 2015, 58 malaria cases were reported in Danyang City, with an average annual
      incidence rate of 0.6/105. Among the cases reported, vivax malaria accounted for
      65.52% (38/58), falciparum malaria accounted for 5.17% (3/58), oval malaria
      accounted for 1.72% (1/58), and unclassified subtype accounted for 27.59%
      (16/58). The local infection cases accounted for 31.03% (18/ 58), and the
      imported cases accounted for 68.97% (40/58). There were no local infections since
      2011. Anopheles sinensis, the only malaria vector in Danyang City, was still
      prevalent, but its density was low. CONCLUSIONS: Imported malaria poses a serious
      threat to the malaria elimination achievements in Danyang City, and the
      surveillance and disposal of imported malaria need to be strengthened.

PMID- 29469452
TI  - [Preparation of recombinant retrovirus pRevTRE-E77.43 and its protective effect
      in a mouse model of Schistosoma japonicum infection].
AB  - OBJECTIVE: To explore the biological functions of E77.43, a gene segment of
      Microtus fortis, in treating Schistosoma japonicum infection. METHODS:
      Recombinant retroviral vectors of pRevTRE-E77.43 was constructed, and recombinant
      retroviral vectors were transfected into PA317 cells, and the stable cell lines
      were obtained by hygromycin screening, followed by the packaging, concentration
      and purification of recombinant retrovirus. The virus was transferred to the mice
      infected by S. japonicum via intravenous or intraperitoneal injection, through
      which the express of target gene and the treatment function in vivo were
      observed. RESULTS: The experiment showed the recombinant virus injected mice
      could efficiently express E77.43 on the 7th day after the injection which lasted
      for forty-five days thereafter. A significant reduction in adult worms (31.0%)
      and a high reduction (35.0%) in liver eggs were induced by pRevTRE-E77.43, while
      the reduction in adult worms and that in liver eggs was 1.2% and 0.9% induced by
      pRevTRE respectively (t = 3.524, 9.485, both P<0.01). CONCLUSIONS: pRevTRE-E77.43
      could be used for the treatment of S. japonicum infection, indicating that E77.43
      may involve in the natural resistance of M. fortis to S. japonicum infection.

PMID- 29469453
TI  - [Analysis of schistosomiasis endemic status of national surveillance sites in
      Yunnan Province, 2016].
AB  - OBJECTIVE: To master the prevalence status of schistosomiasis in Yunnan Province
      in 2016, so as to provide the evidence for formulating the control strategy and
      intervention measures. METHODS: The schistosomiasis heavy-endemic villages were
      selected from each of 18 endemic counties as the survey sites. Then, the
      serological and etiological tests were carried out in the local residents and
      floating population, and the infection status of the livestock, field feces and
      Oncomelania hupensis snails were surveyed. RESULTS: The serum positive rate of
      schistosomiasis of local residents was 8.78% and the serum positive rate was
      2.26% of floating population. No schistosome eggs were found in the stool
      examinations in the population. The area with snails was 80.054 6 hm2 in 2016
      with an increasing rate of 45.47% compared to that in 2015. The average density
      of living snails was 0.031 7/0.1 m2. No schistosome-infected snails were found
      for the last four years and no new area with snails was found for the last three
      years. No positive livestock or feces were found. CONCLUSIONS: The
      schistosomiasis epidemic situation is stabilized in Yunnan Province in 2016.
      However, the area with snails and the number of living snails are increasing, and
      therefore, the schistosomiasis epidemic risk still exists. So, the comprehensive
      control measures should be strengthened continuously.

PMID- 29469454
TI  - [Clinical features of 14 cases of cerebral schistosomiasis in Jiangxi Province].
AB  - OBJECTIVE: To discuss the clinical features of cerebral schistosomiasis. METHODS:
      The clinical data of fourteen patients with cerebral schistosomiasis from March
      2010 to March 2016 were collected and analyzed retrospectively. RESULTS: The
      schistosomiasis immunological tests of sera and cerebrospinal fluids from the
      fourteen patients were all positive. Eosinophils increased in ten cases, and the
      proportion was 5.1%-60.3%. Schistosoma eggs were found in seven cases by the
      fecal Kato-Katz method. Fourteen cases were all infected with Schistosome
      japonicum. Twelve cases were diagnosed as chronic type, and two cases as acute
      type. Thirteen patients received medical treatment, of which twelve were cured,
      and one improved. One patient received the surgical resection of the lesion.
      CONCLUSIONS: The clinical manifestations of cerebral schistosomiasis mainly
      include seizure, headache, dizziness and fever. In the enhanced head magnetic
      resonance imaging (MRI), the lesions are clustered and merged into lumps, which
      is the characteristic image of cerebral schistosomiasis japonica. The
      praziquantel treatment can achieve a good prognosis.

PMID- 29469456
TI  - [Epidemiological analysis of imported malaria in Yancheng City from 2011 to
      2015].
AB  - OBJECTIVE: To understand the epidemiological trend of imported malaria and its
      monitoring and control effect in Yancheng City from 2011 to 2015, so as to
      provide the evidence for adjusting the prevention and control strategy. METHODS:
      The data of malaria surveillance, epidemic, prevention and control were collected
      and analyzed in the districts and counties of Yancheng City from 2011 to 2015.
      RESULTS: From 2011 to 2015, there were 104 imported malaria cases reported, and
      the most cases (52 cases, 50%) were reported from Jianhu County. Most of the
      cases were males (only 2 females), the average age was 38.8 years, and the
      occupation was mainly labor service worker abroad (94 cases, 97%). The infection
      source of these cases mainly came from Africa. From 2011 to 2015, 151 980 fever
      patients received malaria blood tests, and the positive rate was 0.07%.
      Falciparum malaria cases were the most (90 cases, 86.5%). The confirmed
      diagnostic rate of malaria within 24 hours increased year by year. All the 104
      patients received the standardized treatment. CONCLUSIONS: There are no local
      malaria cases in Yancheng City from 2011 to 2015, and in the next stage, the
      monitoring and prevention should be focused on imported malaria, including
      shortening the confirmed diagnostic time and improving the diagnostic efficiency.

PMID- 29469455
TI  - [Case analysis and control strategy of imported malaria in Qingcheng District,
      Qingyuan City from 2011 to 2016].
AB  - OBJECTIVE: To understand the characteristics of imported malaria cases in
      Qingcheng District, Qingyuan City and explore the strategies and priorities in
      prevention and control, so as to provide the evidence for improving the
      diagnosis, treatment and management of imported malaria. METHODS: The data of
      imported malaria as well as the case epidemiological investigations were
      collected and retrospectively analyzed for the species composition, original
      countries, population distribution, regional distribution, onset situation,
      diagnosis, treatment, etc. in Qingcheng District from 2011 to 2016. RESULTS: The
      number of imported malaria cases was 13 from 2011 to 2016. All the patients were
      confirmed by laboratory, and of which, 9 patients infected with Plasmodium
      falciparum, 1 with P. vivax, 1 with P. ovale and 2 with mixed infections (P.
      vivax and P. falciparum). The yearly incidence of imported malaria presented an
      uptrend. The infection sources of all the patients were from African countries,
      and the exported labor workers and travelers for business from malaria endemic
      areas were the high risk population. The reported time was mainly January,
      February, November and December (11/13, 84.62%). All the patients were male, and
      the majority of them (12/13, 2.31%) were 21-60 years old. The median time from
      onset to seeing a doctor was 2.5 days and the median time from seeing a doctor to
      being diagnosed was 1.9 day. Six patients (46.15%) were diagnosed as other
      diseases at the first visit to a doctor, and one patient died of falciparum
      malaria because of delayed diagnosis. CONCLUSIONS: The incidence of overseas
      imported malaria presents an uptrend in Qingcheng District. It is necessary to
      further strengthen the professional training in medical staff to improve the
      diagnosis and treatment of malaria cases. It is also necessary to strengthen the
      multisectoral cooperation, establish the surveillance in the high risk
      population, etc.

PMID- 29469457
TI  - [Epidemiological characteristics of malaria in Yizheng City from 2000 to 2016].
AB  - OBJECTIVE: To explore the epidemiological characteristics of malaria in Yizheng
      City, so as to provide a reference for formulating the control strategy in the
      future. METHODS: The data of malaria case reports and prevention and control work
      in Yizheng City were collected and retrospectively analyzed. RESULTS: Totally 55
      malaria cases were found in Yizheng City from 2000 to 2016 with an average
      incidence of 0.56/105. The malaria cases were local cases from 2000 to 2010 and
      since 2011 they were all imported cases. CONCLUSIONS: The endemic situation of
      malarial in Yizheng City is stable and no local infection cases occur in this
      place for six consecutive years. The imported cases should be paid more attention
      to in the future control work.

PMID- 29469458
TI  - [Cryptosporidium infection in Nanjing City from 2015 to 2016].
AB  - OBJECTIVE: To investigate the status of Cryptosporidium infection in the
      population in Nanjing City so as to provide the evidence for the prevention and
      control of cryptosporidiosis. METHODS: A total of 100 fecal samples were
      collected from each of three districts (Liuhe, Qixia and Gaochun) and one
      hospital (Nanjing Zhongda Hospital) in 2015 and 2016 respectively. The fecal
      samples were detected for Cryptosporidium with microscopy (by using the gold
      amine phenol-modified acid-fast staining) and the positive samples were detected
      again for the molecular biology confirming by using the fluorescence quantitative
      PCR. RESULTS: During the two years, 581 cases of normal population who lived in
      the city were surveyed and no Cryptosporidium infection was found. Among 202
      cases of outpatients with chronic diarrhea, there were 9 Cryptosporidium positive
      cases with the microscope scanning method (4.46%), and among the 9 cases, 7 cases
      showed obvious logarithmic amplification curves showing positive Cryptosporidium
      nucleic acid, but 2 cases without the obvious logarithmic amplification curves,
      and the Cryptosporidium nucleic acid positive rate was 3.47%. CONCLUSIONS:
      Cryptosporidium infection is not found in the normal population of Nanjing City,
      but the Cryptosporidium infection is found in the chronic diarrhea patients. The
      results imply that we should strengthen the detection of Cryptosporidium in the
      chronic diarrhea patients, so as to provide the evidence for improving the
      diagnosis and treatment of cryptosporidiosis.

PMID- 29469459
TI  - [A sero-epidemiological survey of Toxoplasma gondii infections in high-risk
      populations in Hangzhou City].
AB  - OBJECTIVE: To understand the status of Toxoplasma gondii infections and the
      awareness of toxoplasmosis prevention and control knowledge among high-risk
      populations in Hangzhou City. METHODS: The serum anti-T. gondii antibodies were
      detected in 100 HIV/AIDS patients, 100 cancer patients, 100 pregnant women and
      100 healthy controls, and the awareness of toxoplasmosis prevention and control
      knowledge was investigated using a questionnaire. RESULTS: The sero-prevalence of
      T. gondii infection was 31%, 30% and 21% in HIV/AIDS patients, cancer patients
      and pregnant women, which was all significantly higher than in healthy controls
      (chi2 = 14.68, 13.96 and 7.56, all P values < 0.01). The pregnant women had a
      high awareness rate of toxoplasmosis prevention and control knowledge, and the
      healthy controls had a low awareness rate. In addition, the subjects had a low
      awareness rate regarding the questions including"Do you know the damages of
      Toxoplasma gondii infections?", "Do you know that consumption of raw or uncooked
      meat may cause Toxoplasma gondii infections?", and"Do you know that contact with
      contaminated soil may cause Toxoplasma gondii infections?". CONCLUSIONS: The sero
      prevalence of T. gondii infection is high among the high-risk populations in
      Hangzhou City, including the HIV/AIDS patients, cancer patients and pregnant
      women, and these high-risk populations have a low awareness rate of some
      toxoplasmosis prevention and control knowledge. Therefore, it is essential to
      improve the health education of toxoplasmosis prevention and control knowledge
      among the high-risk populations, so as to effectively prevent and control human
      T. gondii infections.

PMID- 29469460
TI  - [Knowledge, attitude and practice (KAP) of foodborne parasitic diseases among
      middle school students in Xuzhou City].
AB  - OBJECTIVE: To investigate the status of knowledge, attitude and practice (KAP) of
      foodborne parasitic diseases among middle school students in Xuzhou City, so as
      to provide a reference to the health education. METHODS: A total of four middle
      schools were selected and their students were investigated with the basic
      information questionnaire and questions of foodborne parasitic diseases. RESULTS:
      The awareness rates of parasitic diseases, hazards and transmission were 56.50%,
      66.33% and 70.50% respectively. The awareness rates of transmission of the
      diseases in the senior high school students and urban students were higher than
      those in the junior middle school students and rural students (chi2 = 8.684,
      8.470, both P < 0.05). The formation rates of not drinking raw water and not
      eating raw food were higher among the female students than those among the male
      students (chi2 = 7.675, 15.230, both P < 0.05). The formation rate of not eating
      raw food was higher among the senior high school students than that among the
      junior middle school students (chi2 = 49.276, P < 0.001), and the formation rates
      of washing hands before meals and not keeping pets were higher among the urban
      students than those among the rural students (chi2 = 5.833, 13.443, both P <
      0.05). Totally 64.83% of the students would not eat food that might be infected
      with foodborne parasites, and the proportion of girls was higher than that of the
      boys (chi2 = 11.690, P < 0.05), and 20.5% of the students would suggest others
      not eating food that might be infected with foodborne parasites, and 81% of the
      students would plan to get rid of bad habits. CONCLUSIONS: The cognition of
      foodborne parasitic diseases is poor among the middle school students in Xuzhou
      City. The health education work on foodborne parasitic diseases should be
      strengthened.

PMID- 29469461
TI  - [Effects and cost of four formulations of niclosamide ethanolamine salt in
      Oncomelania hupensis snail control in field].
AB  - OBJECTIVE: To investigate the effects and cost of four formulations of
      niclosamide ethanolamine salt in Oncomelania hupensis snail control in the field
      in marshland and lake regions, so as to provide the evidence for drawing up the
      plan of molluscicide using in schistosomiasis endemic areas. METHODS: One
      drainage channel and one channel without water in the same area with snails in
      Jiangling County, Jingzhou City were selected as the research fields. The
      drainage channel was divided into 9 sections, except one section as a blank
      control group where the natural death rate of snails was observed only, and the
      remaining 8 sections were taken as the observation groups, where different
      dosages of 4% niclosamide ethanolamine salt powder, 5% niclosamide ethanolamine
      salt granules, 25% niclosamide ethanolamine salt suspending agent, 26%
      metaldehyde and niclosamide ethanolamine salt suspending agent, and 50%
      niclosamide ethanolamine salt wettable powder were used respectively. The channel
      without water were divided into 4 sections, except one section as a blank control
      group, the other 3 segments were taken as the observation groups, where 4%
      niclosamide ethanolamine salt powder, 5% niclosamide ethanolamine salt granules,
      and 50% niclosamide ethanolamine salt wettable powder were used respectively.
      Before and after spraying molluscicide for 7 days and 15 days, the system
      sampling method was used to observe the effects of snail control. Meanwhile, the
      unit cost method was used to calculate the costs of the different mulluscicide
      formulations abovementioned in unit area (1 m2). RESULTS: In the field at the
      drainage channel, the snail mortality rates of the groups spraying 4% niclosamide
      ethanolamine salt powder (50 g/m2), 5% niclosamide ethanolamine salt granules (40
      g/m2), 25% niclosamide ethanolamine suspending agent, 26% metaldehyde and
      niclosamide ethanolamine salt suspending agent, and 50% niclosamide ethanolamine
      salt wettable powder (2 g/m2 and 4 g/m2) for 7 days were 79.52%97.87%, while the
      rates after spraying for 15 days were 71.00%-96.30%, and compared with those
      before spraying, the differences were statistically significant (all P < 0.01).
      For the groups spraying with 2 g/m2 or 4 g/m2 suspending agent as well as
      wettable powder for 7 days, the snail mortality rates were significantly
      different (both P < 0.05). In the field at the channel without water, the snail
      mortality rates of the 3 observation groups after spraying molluscicide for 7
      days were 97.14%-100%, while for 15 days were 94.32 %-100%, and compared with the
      rates before spraying, all the differences were statistically significant (all P
      < 0.01). The unit costs per 1 m2 of the molluscicide abovementioned were ranged
      from 0.280 Yuan to 0.416 Yuan. CONCLUSIONS: In marshland area inside embankment,
      the molluscicide formulations of the powder and granule are suitable for the
      environments without water or with instability water level, while the
      molluscicide formulations of the suspended agents and wettable powder are
      suitable for the water environment. Though the unit cost of powder is the lowest,
      the molluscicide in this formulation flies away seriously.

PMID- 29469462
TI  - [Measures and effects of schistosomiasis elimination in Wujin District, Changzhou
      City].
AB  - OBJECTIVE: To understand the measures and effects of schistosomiasis elimination
      in Wujin District, Changzhou City, so as to provide the reference for other
      similar areas. METHODS: The data of schistosomiasis prevention and control were
      collected and analyzed in Wujin District, Changzhou City from 1995 to 2015.
      RESULTS: From 1995 to 2015, the accumulated area for investigating Oncomelania
      hupensis snail habitats was 15 934.01 hm2 in Wujin District, and the accumulated
      area with snail habitats was 34.61 hm2, but no schistosome-infected snails were
      found. The area of snail control by molluscicides was 234.59 hm2, and the area of
      snail control by environmental reform was 84.48 hm2 in 18 key points. There were
      259.3 thousand person-times receiving the examinations for schistosomiasis, and
      there were 17 314 head of livestock receiving the examinations for
      schistosomiasis, but no schistosome-infected cases were found. There were 204 2
      person-times receiving the extensive chemotherapy. The popularizing rate of
      sanitary toilets was 99.25% in the whole district. The awareness rate of
      schistosomiasis control knowledge was 98.08% and the formation rate of proper
      behaviors was 97.82% in the population. CONCLUSIONS: In Wujin District, the aim
      of schistosomiasis elimination has been performed through the active control
      measures. However, there are still social and natural risk factors of re-endemic
      of schistosomiasis, and therefore, the schistosomiasis monitoring work still
      should be strengthened.

PMID- 29469463
TI  - [Carpoglyphus lactis infestation in stored traditional Chinese medicine Arillus
      longan].
AB  - OBJECTIVE: To investigate the breeding of Carpoglyphus lactis in the storage
      Arillus longan, so as to provide the evidence for preventing the harm of C.
      lactis to traditional Chinese medicine. METHODS: Chinese herbal medicine
      warehouses were chosen as survey sites according to the breeding habits of mites,
      and the A. longan samples were stored more than 6 months. The mites were isolated
      and identified under a microscope. RESULTS: The C. lactis breeding rate was 20.0%
      (4/20) and the breeding density was 184.95 per sample. The constitute rates of
      adult, larva, dormancy body and egg were 58.39%, 30.41%, 0.06%, and 11.14%
      respectively. CONCLUSIONS: The breeding density of C. lactis is high in the
      stored A. longan, so the control and prevention of human intestinal acariasis
      should be strengthened.

PMID- 29469464
TI  - [Investigation and morphological observation of Histiostoma feroniarum breeding
      in Chinese herbal medicine Rhizoma Zingiberis].
AB  - OBJECTIVE: To understand the breeding situation of Histiostoma feroniarum in
      Chinese herbal medicine Rhizoma Zingiberis. METHODS: The Rhizoma Zingiberis sold
      on the market was selected and brushed. The dust from Rhizoma Zingiberis was
      screened under a microscope to search the mites. The mites were made into
      specimens to identify the species. RESULTS: The mites were H. feroniarum. Totally
      14 mites were found in 100 g dust sample, with the density of breeding of 0.14/g.
      CONCLUSIONS: H. feroniarum could breed in Chinese herbal medicine Rhizoma
      Zingiberis, and the prevention and control measures should be adopted.

PMID- 29469465
TI  - [Acarus farris hypopus found in stored wheat].
AB  - OBJECTIVE: To observe the morphological characteristics of Acarus farris hypopus.
      METHODS: The breeding mites from stored wheat samples were separated by a shake
      sieve and direct microscope. The isolations were used for slide preparation, and
      then the slide was observed under a light microscope for mite identification.
      RESULTS: The A. farris hypopus was found in the collected wheat samples. Under
      the microscope the boundary between the propodosoma and hysterosoma of the
      hypopus was obvious. The bristles on the hysterosoma were short, and the abdomen
      had a sucker plate. CONCLUSIONS: There is A. farris hypopus breeding in the
      storage wheat, and its morphological characteristics is similar with the
      characteristics of A. siro hypopus.

PMID- 29469466
TI  - [Preliminary research on prokaryotic expression and immune protection of
      triosephosphate isomerase of Toxoplasma gondii].
AB  - OBJECTIVE: To study the prokaryotic expression and immune protection of
      triosephosphate isomerase (TPI) of Toxoplasma gondii in mice. METHODS: Total RNA
      was extracted from toxoplasma tachyzoites, and TPI fragment was amplified by PCR
      and cloned into the prokaryotic expression vector pET-28a (+). The target protein
      was induced with IPTG and purified by Ni-NTA affinity chromatography. The mice
      were immunized 4 times by emulsified TPI with adjuvant, and the last time was the
      strengthen immunization. At the same time, an adjuvant group and a normal group
      were set as controls. The blood samples were got from the tail vein of the mice,
      and the serum antibody titres were detected. All the mice were challenged with
      400 toxoplasma tachyzoites to observe the survival time. RESULTS: The TPI gene
      was amplified from T. gondii cDNA by PCR. The recombinant vector TPI/pET-28a (+)
      was usefully constructed, and the TPI protein was expressed and purified. The
      serum antibody titre could be more than 100 thousand. After infected with
      toxoplasma tachyzoites, the survival time of the mice in the experimental group
      was longer than that of the mice in the control groups. CONCLUSIONS: The TPI
      protein of T. gondii could trigger the immunoprotection against T. gondii
      challenge in the mice.

PMID- 29469467
TI  - [Study on Oncomelania hupensis snails infected with Schistosoma japonicum
      miracidia under different conditions in snail-existent non-endemic areas of
      schistosomiasis in Nantong City].
AB  - OBJECTIVE: To understand the forming cause of the Oncomelania hupensis snail
      existent non-endemic areas of schistosomiasis (SENEAS), and to verify the
      conclusion of previous studies, so as to provide the evidence for schistosomiasis
      monitoring in such areas in Nantong City, Jiangsu Province. METHODS: The
      controlled field tests were carried out to observe the O. hupensis snails
      artificially infected by schistosome miracidia in SENEAS. The influence of the
      soil from SENEAS and the endemic areas on O. hupensis snails artificially
      infected by miracidia were observed. RESULTS: All the experimental snails could
      be infected by schistosome miracidia except the smooth-shell snails from Tangyuan
      Village in the controlled field test environment of SENEAS or the endemic areas.
      The infection rates of the smooth-shell snails were lower than those of the
      ribbed-shell snails, but there were no statistically significant differences. The
      mortality rates of the smooth-shell snails were higher than those of the ribbed -
      shell snails, which were statistically significant (chi2Xindian = 135.118,
      chi2Shuangdian = 122.836, chi2Baipu =154.436, chi2Dingyan = 138.288, chi2Control
      = 151.923, all P < 0.01). There were no significant differences in the infection
      rates of snails between each test group of the soil from SENEAS and the endemic
      areas (chi2Rugao = 0.071, chi2Rudong = 0.216, both P > 0.05). Also there was no
      significant difference between each test group and the control group without soil
      (chi2 = 7.148, P > 0.05). CONCLUSIONS: It is likely to form the spread of
      schistosomiasis in SENEAS in Nantong City with sufficient amount of infection
      source of schistosomiasis imported. It is still necessary to implement the
      surveillance of schistosomiasis and O. hupensis snails in Nantong City.

PMID- 29469468
TI  - [Expression profiles of circulatingmicroRNAs in newly-developed advanced
      schistosomiasis patients].
AB  - OBJECTIVE: To study the expression profiles of circulating microRNAs (miRNAs) in
      newly-developed advanced schistosomiasis patients. METHODS: Ten healthy controls
      (Group 1), ten patients with schistosomiasis history (without advanced
      schistosomiasis, Group 2) and ten patients with newly-developed advanced
      schistosomiasis (Group 3) were randomly selected from Jiangsu Province. The
      expression profiles of 570 human related circulatingmiRNAs were measured and
      analyzed with the Agilent Human microRNAs microarray Rel 12.0. RESULTS: Compared
      to the healthy controls, four miRNAs were up-regulated, while 16 miRNAs were down
      regulated in the patients with newly-developed advanced schistosomiasis.
      Moreover, six miRNAs were up-regulated, while 21 miRNAs were down-regulated in
      the patients in Group 2. Among of them, the expression level of miR-383 was
      significantly decreased by 4.23 and 11.82 folds in Group 2 and Group 3,
      respectively. CONCLUSIONS: There are significant differences among the healthy
      controls, patients with schistosomiasis history (without advanced
      schistosomiasis) and the patients with newly-developed advanced schistosomiasisin
      the expression profiles of circulatingmiRNAs. Moreover, circulating miR-383 might
      be involved in the development of newly-developed advanced schistosomiasis.

PMID- 29469469
TI  - [Design and development of an online system of parasite's images for training and
      evaluation].
AB  - OBJECTIVE: To design and develop an online training and evaluation system for
      parasitic pathogen recognition. METHODS: The system was based on a Parasitic
      Diseases Specimen Image Digitization Construction Database by using MYSQL 5.0 as
      the system of database development software, and PHP 5 as the interface
      development language. It was mainly used for online training and evaluation of
      parasitic pathology diagnostic techniques. RESULTS: The system interface was
      designed simple, flexible, and easy to operate for medical staff. It enabled full
      day and 24 hours accessible to online training study and evaluation. Thus, the
      system broke the time and space constraints of the traditional training models.
      CONCLUSIONS: The system provides a shared platform for the professional training
      of parasitic diseases, and a reference for other training tasks.

PMID- 29469470
TI  - [Implementation of Oncomelania hupensis monitoring system based on Baidu Map].
AB  - OBJECTIVE: To construct the Oncomelania hupensis snail monitoring system based on
      the Baidu Map. METHODS: The environmental basic information about historical
      snail environment and existing snail environment, etc. was collected with the
      monitoring data about different kinds of O. hupensis snails, and then the O.
      hupensis snail monitoring system was built. Geographic Information System (GIS)
      and the electronic fence technology and Application Program Interface (API) were
      applied to set up the electronic fence of the snail surveillance environments,
      and the electronic fence was connected to the database of the snail surveillance.
      RESULTS: The O. hupensis snail monitoring system based on the Baidu Map were
      built up, including three modules of O. hupensis Snail Monitoring Environmental
      Database, Dynamic Monitoring Platform and Electronic Map. The information about
      monitoring O. hupensis snails could be obtained through the computer and
      smartphone simultaneously. CONCLUSIONS: The O. hupensis snail monitoring system,
      which is based on Baidu Map, is a visible platform to follow the process of
      snailsearching and molluscaciding.

PMID- 29469471
TI  - [Progress of molecular detection of Schistosoma].
AB  - Schistosomiasis diagnosis plays an important role in the schistosomiasis control.
      The early detection of schistosomiasis can help to find the infectious source and
      prevent advanced schistosomiasis effectively. Up to now, serodiagnosis and
      parasitological diagnosis are used commonly to detect the infection of
      Schistosoma. As the schistosomiasis control program continues in China, the
      infection rate and infection intensity of Schistosoma japonicum are decreased
      significantly, which makes the serodiagnosis and parasitological diagnosis
      limited for lacking of sensitivity and timeliness. The molecular diagnosis has
      been developed greatly because of its timeliness, high specificity and
      sensitivity, which promotes the development and improvement of schistosomiasis
      diagnosis. In the endemic areas where schistosomiasis is limited and the
      infection rate is low, the molecular diagnosis provides a potential platform for
      the early detection and micro detection efficiently. Here, we provide a review
      that mainly emphasizes the progress of molecular detection of schistosomiasis.

PMID- 29469472
TI  - [Spatio-temporal variations of origin, distribution and diffusion of Oncomelania
      hupensis in Yangtze River Basin].
AB  - As the only intermediate host of Schistosoma japonicum, Oncomelania hupensis in
      China is mainly distributed in the Yangtze River Basin. The origin of the O.
      hupensis and the spatio-temporal variations of its distribution and diffusion in
      the Yangtze River Basin and the influencing factors, as well as significances in
      schistosomiasis elimination in China are reviewed in this paper.

PMID- 29469473
TI  - [Role of Rho GTPases in the immune regulation of infection and inflammation].
AB  - The Rho subfamily of GTPase belongs to the Ras superfamily of small GTP binding
      protein, it is a nucleotide dependent protein, which plays a "molecular switch"
      function in the signal transduction process and control of numerous signaling
      pathways. Rho protein has many biological effects on cytoskeleton or target
      proteins as a signal converter in signal transduction, such as the regulation of
      membrane transport function, cell migration, cell adhesion, and cell
      proliferation. It also plays a very important role in the infection and immune
      inflammation of the body. Rho protein is widely distributed in related immune
      cells, such as T cells, B cells, NK cells and so on. When the body is infected by
      microorganism, the immune inflammatory reaction will be regulated through a
      series of signal transduction mechanism, and Rho GTPases signal transduction
      mechanism is one of the important signal pathways. In this paper, we conclude
      that Rho GTPases how to regulate the body's immune response through its signal
      pathway, and ultimately affect the body's immune response.

PMID- 29469474
TI  - [Clinical analysis of 12 cases of paragonimiasis].
AB  - OBJECTIVE: To analyze the clinical characteristics of paragonimiasis and improve
      the level of diagnosis and treatment. METHODS: A retrospective analysis was made
      of 12 cases of paragonimiasis. RESULTS: All the paragonimiasis patients had the
      epidemiological history, 83.33% of them had the obvious blood eosinophil
      increase, and 83.33% of them had the positive antibody against Paragonimus.
      Praziquantel oral treatment had a curative effect and little adverse reaction.
      CONCLUSIONS: The clinical symptoms and signs of paragonimiasis are complex and
      diverse, and the doctors should pay attention to the inquiry of epidemiological
      history, blood eosinophil increase and positive antibody against Paragonimus.

PMID- 29469475
TI  - [Report of three death cases of imported falciparum malaria in Wenzhou City].
AB  - The three death cases of falciparum malaria in Wenzhou City were all imported
      from Africa. One patient died on 10 January 2007 because of severe clinical
      symptoms after hospitalization. The second case was initially misdiagnosed as
      influenza in primary health and medical institution. The patient's condition
      quickly worsened and died of Plasmodium falciparum infection on 5 March 2011. The
      third patient belonged to "non-identity" person, and there were no detailed
      information and epidemiological history on admission, which resulted in the
      delayed diagnosis, disease exacerbation and death. In conclusion, the health
      education should be provided to the people who return from Africa and also to
      medical workers in order to reduce the mortality of falciparum malaria.

PMID- 29469476
TI  - [Strengthening the control of goat schistosomiasis to facilitate the progress
      towards elimination of schistosomiasis in China].
AB  - Although great success has been achieved in schistosomiasis control,
      schistosomiasis japonica remains a publichealth concern in China. Schistosoma
      japonicum is found to naturally infect over 40 mammalian animals. The
      implementation of the integrated schistosomiasis control strategy emphasizing
      infectious source control since 2004, which integrates replacement of bovines
      with machines, breeding domestic animals in fences, building safe pastures and
      chemotherapy of infected bovines, results in a clear-cut reduction in the
      prevalence of S. japonicum infection in both humans and bovines, as well as the
      areas of infected snail habitats, and the national schistosomiasis control
      program is moving from transmission control towards transmission interruption and
      elimination. It has been found that goat is highly susceptible to S. japonicum
      infection, and previous epidemiological data have shown a high prevalence of
      infection in goat. However, the role of goat in the transmission of
      schistosomiasis japonica has not been paid much attention, and there are few
      systematic surveys to evaluate the role of goat in schistosomiasis transmission
      in China to date. Professor Liang Yousheng's group investigated S. japonicum
      development and reproduction (egglaying) in goat body, environmental
      contamination by goat feces, and the effect of temperature and humidity on the
      survival of S. japonicum eggs in goat feces. Their findings further demonstrate
      the role of goat in the transmission of schistosomiasis japonica. In addition,
      they proposed, based on their findings and previous reports, that the management
      of goat should be integrated into the national schistosomiasis control program in
      China, since goat is virtually one of the major infectious sources of
      schistosomiasis japonica in China. Moreover, this group improved the fecal
      hatching test and optimized the parasitological technique for diagnosis of S.
      japonicum infection in goats. These innovative studies fill in the gaps of goat
      schitsosomiasis japonica research in China, and the research outcomes will enrich
      the currently implemented integrated schistosomiasis control strategy emphasizing
      infectious source control, and are believed to play a critical role in
      schistosomiasis elimination in China. Since schistosomiasis seriously affects
      goat husbandry development and local famer income, and goat has become a major
      infectious source of schistosomiasis japonica in China, the control of goat
      schistosomiaiss will facilitate the progress towards the elimination of
      schistosomiasis in China, and the following research priorities are suggested:
      (1) to emphasize the control of goat schistosomiasis, and to integrate the
      comprehensive management of goat into the national schistosomiasis control
      program in China; and (2) to develop new techniques, products and interventions
      for the control of goat schistosomiasis.

PMID- 29469477
TI  - [Role of goat in transmission of schistosomiasis japonica III Development of goat
      feces collector and optimization of fecal hatching technique].
AB  - OBJECTIVE: To develop a simple, feasible goat feces collector to improve the
      collection accuracy and integrity of goat fecal samples without pollution, and to
      modify the miracidium hatching test with a plastic tube to achieve simple,
      standard and comparative procedures, so as to provide technical support for
      pathogenic diagnosis and scientific research of goat schistosomiasis japonica.
      METHODS: According to the body features of goat in marshland regions, a goat
      fecal collector, which was made of coarse fabric cottons, was devised, which was
      able to be fixed onto the goat buttocks and avoid urine pollution. Prior to
      miracidium hatching test, the goat fecal samples were pieced by using a
      mechanical method instead of the conventional artificial piecing method, and the
      effect of mechanical piecing treatment on miracidium hatching was evaluated. A
      filter membrane was added between the tube and rubbery ring to block the floater
      in fecal residues into the tube. The effects on miracidium hatching by using thin
      fat-free cotton, thick fat-free cotton, nylon gauze at 100 pores/25.4 mm2 and 150
      pores/25.4 mm2 were compared. RESULTS: The goat feces collector was composed of
      foreleg fixing garment, hindleg fixing garment and stool bag. The functions of
      the fixing garment were as a fixed collector to allow non-shift and tolerance of
      weight during goat activity, while the major function of stool bag was in storage
      of stool. The goat activity did not affect by the use of collector, and all fecal
      samples were excreted to the bag. This collector was easy to perform and could
      avoid urine pollution, which was reusable after cleaning. Prior to miracidium
      hatching, the goat fecal samples, together with water, were pieced at 18000 to
      23000 r/min for successive three times in a cooking machine, of 10 s each time at
      an interval of 5 s. Mechanical piecing had no clear-cut effect on miracidium
      hatching of eggs in fecal samples. A total of 541, 620, 344 and 211 miracidia
      were detected by using the miracidium hatching test with nylon gauze at 100
      pores/25.4 mm2 and 150 pores/25.4 mm2, thin fat-free cotton and thick fat-free
      cotton respectively, indicating a better detection efficacy by using nylon gauze
      at 100 pores/25.4 mm2 and 150 pores/25.4 mm2. CONCLUSIONS: The goat fecal
      collector is a easy-to-perform, accurate, unpolluted and reusable device to
      collect goat feces, which is suitable for pathogenic diagnosis of goat
      schistosomiasis. Mechanical piecing and use of nylon gauze at 150 pores/25.4 mm2
      allow a simple, accurate and stable technique for parasitological diagnosis of
      schistosomiasis japonica, which provides a reliable tool for schistosomiasis
      control and research.

PMID- 29469478
TI  - [Role of goat in transmission of schistosomiasis japonica III Effect of
      temperature and humidity on survival of eggs in goat feces and egg survival in
      natural environments].
AB  - OBJECTIVE: To investigate the survival of Schistosoma japonicum eggs in goat
      feces in natural marshlands and the factors affecting its survival, so as to
      provide evidences for understanding of the role of eggs in goat feces in the
      transmission of schistosomiasis and the development of the interventions
      pertaining to disease control and elimination. METHODS: The goat animals of
      schistosomiasis japonica were modeled in laboratory, and the feces of infected
      goat were collected. In laboratory, the effects of environmental temperature and
      water content in goat feces on egg hatching were evaluated, and in the field, the
      effect of duration of goat feces on marshland on egg hatching and the effect of
      direct sunshine on egg survival were evaluated. RESULTS: At 25 degrees C in
      laboratory, the hatching rate of eggs in goat feces washigh-positively correlated
      with the water content in goat feces (r = 0.87). If the water content reduced to
      7.6% in goat feces, the eggs in goat feces lost the ability to hatch. Under the
      same water content in goat feces, the hatching rate of eggs gradually decreased
      with the extension of the duration of exposure of goat feces to -5  degrees C,
      which reduced to 0 following 5 h exposure. At 5, 15 and 25  degrees C, the
      hatching rates of eggs gradually decreased with the extension of the duration of
      exposure of goat feces, and themiracidium hatching ratesof eggs were 2.3%, 5% and
      0.9% respectively following the exposure for 52 d. At 35 degrees C, the hatching
      rate of eggs gradually decreased with the extension of the duration of exposure,
      which reduced to 0 following 13 d exposure. In winter (-2-10  degrees C), the
      hatching rate of eggs gradually decreased with the extension of the duration of
      exposure of goat feces on marshlands, which reduced to 0 after 21 d of exposure,
      and in spring (16-19  degrees C), the hatching rate of eggs gradually decreased
      with the extension of the duration of exposure of goat feces on marshlands, which
      reduced to 0.9% after 5 d of exposure. At the same time point on the same
      marshland, the hatching rate of eggs in goat feces exposed to marshlands with
      direct sunshine was lower than that without direct sunshine. CONCLUSIONS: The
      survival of S. japonicum eggs in goat feces is associated with environmental
      temperature and water content (humidity) in goat feces, and the temperature and
      humidity are major natural factors affecting egg hatching.

PMID- 29469479
TI  - [Role of goat in transmission of schistosomiasis japonica III Environmental
      contamination by goat feces and prediction of environments at high risk of S.
      japonicum infection].
AB  - OBJECTIVE: To quantitatively estimate the range and area of environmental
      contamination by the feces of Schistosoma japonicum-infected that were freely
      grazed, so as to provide the theoretical evidence for the scientific assessment
      of the role of the freely grazed goat in the transmission of schistosomiasis
      japonica and development of control strategy. METHODS: All the fecal samples
      excreted by the infected goat at daytime (12 h) were collected by using a self
      made goat fecal collector, weighed and counted. The quantity and dispersal of the
      feces excreted by the freely grazed goat at daytime under a natural condition
      were investigated, and the walking route and speed of the freely grazed goat at
      daytime were recorded with a multifunction GPS data logger. The maximum range and
      area of the environment contaminated by the feces of the freely grazed goat at
      daytime were estimated, and the maximum range and area of the Oncomelania
      hupensis snails that may be infected by the schistosome miracidium released from
      the eggs in the fecal samples of the freely graze goat at daytime were
      calculated. RESULTS: During the walking along the marshland at daytime (12 h),
      the quantity of the feces execrated by the freely grazed infected goat was (232.8
      +/- 39.8) g per goat, and the fecal samples were composed of (819.2 +/- 152.1)
      pellets. The goat had a mean walking speed of (0.522 7 +/- 0.099 7) km/h, and the
      longest distance, largest radius and largest range of walking activity were
      (6.272 4 +/- 1.195 8) km, 3.136 2 km and (3 191.113 0 +/- 1 189.709 4) hm2 at
      daytime, respectively. The area of the snails that may be infected by the
      miracidium released from the eggs in the fecal samples of the freely graze goat
      (range of key regions for infected snails detection and control) at daytime was
      estimated to be (3 210.717 5 +/- 1 190.907 3) hm2. CONCLUSIONS: The intensity of
      environmental contamination by the eggs in the fecal samples of the freely grazed
      goat is linked to the number of infected goat. The contamination range caused by
      the feces of the freely grazed goat with fixed fences is relatively stably kept
      within the walking range at day-time, and the range and area of goat fecal
      contamination is associated with the number of households that breed goat and the
      distribution of goat fence. The area of the snails that may be infected by the
      miracidium released from the eggs in the fecal samples of the freely graze goat
      is larger than the area of setting contaminated by the eggs in the goat feces,
      indicating that the range of infected snail examination and control is larger
      than the range of goat feces detected.

PMID- 29469480
TI  - [Role of goat in transmission of schistosomiasis japonica IV Schistosome
      development in goat and egg count and distribution in goat feces].
AB  - OBJECTIVE: To describe the growth and development of Schistosoma japonicum in
      goat and the intensity and temporal distribution of eggs excreted by goat feces,
      so as to provide baseline data for the control and elimination of the role of
      goat in the transmission of schistosomiasis. METHODS: The goat animal models of
      schistosomiasis were established, and stool samples were collected for
      parasitological examinations. The number of adult worms recovered, variation of
      schistosomes in goat at different time points post-infection, number of eggs in
      schistosomes, variation in number and temporal profiles of eggs excreted from
      goat feces were observed. RESULTS: Of the 6 schistosome-infected goat, 415 adult
      worms were recovered, with a mean adult worm recovery of 34.58% (range, 23.00% to
      45.50%). Among the 5 goat infected with 200 cercariae each, 47, 93, 77, 74 and 73
      adult worms were recovered 2, 5, 8, 11 and 14 months post-infection,
      respectively. There were (200.00+/-42.33), (226.20+/-45.88), (168.20+/-25.85),
      (183.80+/-55.13) and (190.80+/-53.53) eggs detected in female schistosomes. The
      mean prepatent period of eggs excreted by 10 infected goat was (37.7+/-3.02) d.
      From 2 to 14 months post-infection, 7 batches of goat feces were hatched, and
      there were 30, 23, 14, 1 and 2 times for miracidium intensity of "++++", "+++",
      "++", "+" and "-", respectively, with 42.86%, 32.86%, 20.00%, 1.43% and 2.86%
      constituent ratios of miracidium intensity. CONCLUSIONS: Approximately 1/3 S.
      japonicum cercariae may develop to adults in goats post-infection, and the
      prepatent period of eggs is (37.7+/-3.02) d. There is no remarkable decrease seen
      in the number of adult worms, eggs in female schistosomes and eggs in goat feces
      within 14 months post-infection. Our findings suggest a long duration for
      infected goat in the transmission of schistosomiasis, and there is no evidence to
      prove the "self-cure" phenomenon in goat, indicating that goat is an important
      source of infection for schistosomiasis japonica.

PMID- 29469481
TI  - [Comparison study on sampling methods of Oncomelania hupensis snail survey in
      marshland schistosomiasis epidemic areas in China].
AB  - OBJECTIVE: To optimize and simplify the survey method of Oncomelania hupensis
      snail in marshland endemic region of schistosomiasis and increase the precision,
      efficiency and economy of the snail survey. METHODS: A quadrate experimental
      field was selected as the subject of 50 m*50 m size in Chayegang marshland near
      Henghu farm in the Poyang Lake region and a whole-covered method was adopted to
      survey the snails. The simple random sampling, systematic sampling and stratified
      random sampling methods were applied to calculate the minimum sample size,
      relative sampling error and absolute sampling error. RESULTS: The minimum sample
      sizes of the simple random sampling, systematic sampling and stratified random
      sampling methods were 300, 300 and 225, respectively. The relative sampling
      errors of three methods were all less than 15%. The absolute sampling errors were
      0.221 7, 0.302 4 and 0.047 8, respectively. CONCLUSIONS: The spatial stratified
      sampling with altitude as the stratum variable is an efficient approach of lower
      cost and higher precision for the snail survey.

PMID- 29469482
TI  - [Evaluation of transmission control of schistosomiasis in 19 counties (cities,
      districts) of Hubei Province in 2013].
AB  - OBJECTIVE: To evaluate the schistosomiasis transmission control in 19 counties
      (cities, districts) of Hubei Province in 2013. METHODS: The epidemic villages
      from different counties were randomly sampled by the cluster sampling method as
      the evaluation villages. The schistosome infection status of human and livestock,
      the Oncomelania hupensis snail status, the documents and data of schistosomiasis
      control, acute infection control and health education were investigated in the
      field. RESULTS: The serum examination of schistosome infection was performed to
      29 631 residents, and 2 068 were positive, with a positive rate of 6.98% (0.78% 
      16.47%). The stool examination was performed to 2 021 sero-positive persons, and
      47 cases were stool-positive, with an infection rate of 0.16% (0 - 0.82%). The
      cattle was the main domestic animals in 19 counties (cities, districts), and the
      measures of replacing cattle with machine for cultivation were done in 17
      counties (cities, districts). Totally 105 cattle in Caidian District and Huangpi
      District received stool examinations and no positives were detected. A total of 1
      579.37 hm2 and 31 829 frames in 154 environments were surveyed, and 4 857 snails
      were collected. Of the 1 935 living snails dissected, no infected snails were
      detected. The files regarding the schistosomiasis morbidity and snail status have
      been established in 19 counties (cities, districts) since 2009. CONCLUSIONS: The
      transmission of schistosomiasis in 19 counties (cities, districts) of Hubei
      Province has reached the standard of transmission controlled.

PMID- 29469483
TI  - [Construction and operation status of management system of laboratories of
      schistosomiasis control institutions in Hubei Province].
AB  - OBJECTIVE: To analyze the construction and operation status of management system
      of laboratories of schistosomiasis control institutions in Hubei Province, so as
      to provide the reference for the standardized detection and management of
      schistosomiasis laboratories. METHODS: According to the laboratory standard of
      schistosomiasis at provincial, municipal and county levels, the management system
      construction and operation status of 60 schistosomiasis control institutions was
      assessed by the acceptance examination method from 2013 to 2015. RESULTS: The
      management system was already occupied over all the laboratories of
      schistosomiasis control institutions and was officially running. There were 588
      non-conformities and the inconsistency rate was 19.60%. The non-conformity rate
      of the management system of laboratory quality control was 38.10% (224 cases) and
      the non-conformity rate of requirements of instrument and equipment was 23.81%
      (140 cases). CONCLUSIONS: The management system has played an important role in
      the standardized management of schistosomiasis laboratories.

PMID- 29469484
TI  - [Correlation between malaria epidemic incidence and some natural and social
      factors in high incidence areas of Shandong Province].
AB  - OBJECTIVE: To explore the association between malaria epidemic situation and some
      natural and social factors in high-incidence areas of Shandong Province, so as to
      provide evidences for malaria elimination in these areas. METHODS: Twenty towns
      of 10 counties (cities, districts,) in the high incidence areas of malaria in
      Shandong Province were selected as the study sites, and the residents in the
      study sites were investigated by questionnaires with one household as a unit, so
      as to understand the related natural and social factors. In addition, the malaria
      epidemic data in the study sites from 2006 to 2010 were collected, and the
      correlation between these factors and the epidemic situation of malaria was
      analyzed by Spearman rank correlation and multiple stepwise regression. RESULTS:
      The square root of malaria incidence rate (Y) was negatively related to the rate
      of households using insecticide (X3), and the rate of households using screen
      doors and windows (X4) (both P < 0.05), but was positively related to the rate of
      housing surrounding water environment and exposure ratio (X6) (both P < 0.05).
      The regression equation established was Y = 0.032X5 + 0.048X6-0.495, R2 = 0.973.
      CONCLUSIONS: Malaria incidence is obviously associated with some natural and
      social factors. The measures such as clearing the breeding place of mosquito,
      protecting the exposure population at nightfall, as well as using door-window
      screen and repellents correctly, can effectively control malaria.

PMID- 29469485
TI  - [Changes and significance of inflammatory cytokines in sera of mice chronically
      infected with larvae of Echinococcus granulosus].
AB  - OBJECTIVE: To investigate the levels of cytokines in the sera of mice chronically
      infected with the larvae of Echinococcus granulosus, and explore the mechanisms
      of immune regulation against parasite infection. METHODS: The protoscoleces were
      isolated from the livers and lungs of sheep infected with E. granulosus, and then
      inoculated intraperitoneally to BALB/c mice (2 000 for each mouse), to establish
      the mouse model of E. granulosus infection. The mice in the control group were
      injected intraperitoneally with an equal volume of PBS. The sera of both control
      and infected mice were collected to test the levels of multiple cytokines by
      using the Cytometric Bead Array (CBA) 5 months post-infection. RESULTS: In
      contrast to the control group, the multiple cysts were found in the abdominal
      cavity, livers and lungs of the infected mice. Moreover, the levels of
      inflammatory cytokines such as IL-17A, IL-6, IFN-gamma, MCP-1, IL-12P70 and TNF
      alpha in the sera of the infected mice were significantly higher than those in
      the control group (t = 2.713-9.255, all P < 0.05) while the levels of anti
      inflammatory cytokine IL-10 were elevated post-infection (t = 3.936, P < 0.001).
      CONCLUSIONS: Higher inflammatory cytokines in the mice chronically infected with
      the larvae of E. granulosus, may benefit for the limitation of parasite growth.

PMID- 29469486
TI  - [Effect of prevention and control system for malaria eliminating in Huai'an
      City].
AB  - OBJECTIVE: To investigate the execution and effect of the prevention and control
      system for malaria eliminating in Huai'an City from 2010 to 2015, so as to
      provide the evidence for formulating and adjusting the strategy and measures for
      malaria elimination. METHODS: The data of network malaria reports, blood tests of
      feverish patients, epidemiology investigation forms of case study of malaria
      patients in the report system, and the investigation and disposition forms of
      epidemic foci were collected and analyzed statistically. RESULTS: From 2010 to
      2015, there were 267 malaria cases in total in Huai'an City. Totally 303 016
      feverish patients had blood tests, and 231 of them showed positive and the
      positive rate was 0.08%. The epidemiological case studies showed that all the
      patients were foreign imported cases except 22 local infected vivax malaria cases
      in 2010 and 2011. All the malaria cases were reported after diagnosis within 24
      hours through the directly reported network, and the implementation rate was
      100%. All the malaria cases had an epidemiological investigation within 3 days
      with 100% implementation rate, in which 261 (97.95%) cases were investigated
      within 2 days. All the cases had an epidemical investigation and disposition
      within 7 days with 100% implementation rate, in which 252 (94.38%) cases were
      completed within 5 days. CONCLUSIONS: The implementation rate of malaria
      elimination work mode has reached 100% in Huai'an City from 2010 to 2015, and
      there are no local infected cases in recent four years.

PMID- 29469487
TI  - [Investigation on Aspidogastrea infection in freshwater mussels in Anhui
      Province].
AB  - OBJECTIVE: To investigate the prevalence of trematode Aspidogastrea in freshwater
      mussels in Anhui Province, China. METHODS: The freshwater mussels living in
      different water areas within Anhui territory were harvested and dissected from
      April to May, 2015. Then the flukes were collected from the pericardial cavities
      of the clams into a petri dish containing small amount of saline. After rinsing,
      the flukes were transferred into a bottle containing 70% ethanol for following
      identification by staining of the specimens prepared as previous protocol.
      RESULTS: A total of 3 007 calms in 12 species, including Unio douglasiae (603),
      Acuticosta chinensis (90), Lamprotula caveat (150), Lamprotula leai (250),
      Lanceolaria grayana (47), Anodonta pacifica (60), Anodonta woodiana (350),
      Cuneopsis heudei (100), Solenaia oleivora (150), Cristaria plicata (567),
      Hyriopsis cumingii (550) and Arconaia lanceolata (90) were dissected, in which 1
      467 mussels were infected with the trematode Aspidogastrea, with an infection
      rate of 48.79% (1 467/3 007). Totally, 7 306 flukes belonging to 3 genera under
      the subclass of Aspidogastrea were isolated. These trematodes were genera of
      Aspidogaster, Lophotaspis and Cotylaspis. The infection density was from 1 to 128
      capita for individual positive clam, with a mean infectiosity of 4.98 (7306/1467)
      for each mussel. CONCLUSIONS: The freshwater bivalves living in different water
      areas in Anhui Province are infected with the trematode Aspidogastrea. These
      flukes were identified as Aspidogaster sp. Lophotaspis sp. and Cotylaspis sp.
      belonging to subclass Aspidogastridae of family Aspidogastrea.

PMID- 29469488
TI  - [Cloning, expression and serological evaluation of H3 protein from Echinococcus
      granulosus].
AB  - OBJECTIVE: To clone and express the basement membrane specific heparan sulfate
      proteoglycan core protein (H3), and to evaluate its effect in detection of human
      cystic echinococcosis (CE). METHODS: The H3 gene immunoscreened from the cDNA
      library was cloned into pGEX-4T vector. The recombinant plasmid pGEX-3X-AgB8/3
      was transformed into Escherichia coli BL21 strains and induced by isopropyl-beta
      D-thiogalactopyranoside (IPTG). Then the expressed recombinant protein was
      purified by affinity chromatography and its effect in the detection of CE was
      evaluated by ELISA. Meanwhile, the effects of H3 and two antigens that the
      research group prepared before (purified HCF and rAgB8/2) in CE detection were
      compared. RESULTS: The plasmid pGEX-4T-H3 was successfully constructed and H3 was
      successfully expressed in prokaryotic cells. The sensitivities of the recombinant
      H3, purified HCF and rAgB8/2 in CE detection were 84.0% (68/81), 90.1% (73/81)
      and 77.8% (63/81) respectively, and there was no statistical difference among
      them (chi2 = 4.58, P > 0.05). The cross reactions of recombinant H3 with the sera
      of the patients with CE, cysticercosis and schistosomiasis were 63.3% (19/30),
      16.7% (5/30) and 5.0% (1/20) respectively, and the cross reaction was 0 with the
      sera of healthy people. The specificities of recombinant H3, purified HCF, and
      rAgB8/2 were 80.8% (105/130), 71.5% (93/130) and 82.3% (107/130) respectively,
      and there were no statistical difference among them (chi2 = 5.71, P > 0.05).
      CONCLUSIONS: The recombinant H3 is a potential diagnostic antigen for CE
      detecting.

PMID- 29469489
TI  - [Investigation on human Toxoplasma gondii infections in Nanchang City in 2014].
AB  - OBJECTIVE: To investigate the endemic situation of human Toxoplasma gondii
      infection in Nanchang City in 2014 and analyze the influencing factors, so as to
      provide the evidence for control measures. METHODS: The high-risk population of
      T. gondii infection in Nanchang City was collected as an experiment group, and a
      control group was settled with the ratio of 1?1. The serum tests and epidemiology
      surveys were conducted simultaneously, and the influencing factors were analyzed.
      RESULTS: The total positive rate of human T. gondii was 5.17% (124/2 400) among
      the whole population in Nanchang City in 2014. The positive rate was 7.50% (90/1
      200) in the experiment group and 2.18% (34/1 200) in the control group, and the
      difference was significant (chi2 =26.668, P<0.05). The results of univariate
      analysis indicated that different dietary habits and health habits were closely
      related to the infection of T. gondii (chi2 =16.522, 64.954, both P<0.05). The
      result of Logistic analysis showed that the risk factors of T. gondii infection
      were occupation, educational levels, raising cats, contacting animals or raw
      meat, and eating raw or uncooked beef. CONCLUSIONS: The high risk population of
      T. gondii infection is the key population of the toxoplasmosis control. Unhealthy
      dietary and living habits are key influencing factors of toxoplasmosis, and the
      related health education and surveillance work should be strengthened.

PMID- 29469490
TI  - [Preliminary study on infection status and gene types of Cryptosporidium among
      HIV/AIDS patients in Guangxi].
AB  - OBJECTIVE: To understand the infection status and gene types of Cryptosporidium
      among HIV/AIDS patients in Guangxi Zhuang Autonomous Region. METHODS: The fecal
      samples were collected from 285 HIV/AIDS cases in Nanning, Guilin, Qinzhou,
      Baise, Hechi cities of Guangxi and 150 HIV negative persons in Nanning City. The
      modified acid-fast staining and nested-PCR based on 18S rRNA were employed to
      detect the infection status of Cryptosporidium. The nested PCR products were
      sequenced, and the homology searches and identification for the gene types of
      Cryptosporidium were done by DNAStar software. RESULTS: The infection rate of
      Cryptosporidium in HIV/AIDS patients was 0.70% (2/285), and the rate of those
      with chronic diarrhea was 6.67% (2/30), the latter was significantly higher than
      that of the HIV negative persons (0, 0/150) (P = 0.002). Both the two HIV/AIDS
      patients infected with Cryptosporidium were from Guilin City. By molecular
      identification, the Cryptosporidium strains which the above 2 patients were
      infected with were Cryptosporidium andersoni and Cryptosporidium hominis
      respectively. CONCLUSIONS: Cryptosporidium co-infection can be found in HIV/AIDS
      patients in Guangxi. The genotypes of the infection strains include
      Cryptosporidium andersoni and Cryptosporidium hominis.

PMID- 29469491
TI  - [Prokaryotic expression and identification of rhoptry protein 38 of Toxoplasma
      gondii].
AB  - OBJECTIVE: To explore the biological function of rhoptry protein 38 (ROP38) of
      Toxoplasma gondii, and to identify the reactogenicity of the recombinant protein
      (rROP38). METHODS: The ROP38 was amplified by RT-PCR from T. gondii RH strain,
      and was cloned into prokaryotic expression vector pET-28a (+). The recombinant
      plasmid was transformed into E. coli BL21 (DE3) competent cells. Then the rROP38
      was analyzed by SDS-PAGE and identified by Western blot. RESULTS: SDS-PAGE showed
      that rROP38 was efficient expression with a molecular weight of about 43 kD.
      Western blot showed that rROP38 reacted with antibody of His tag or human
      positive antibody, which indicated that ROP38 had good reactogenicity and could
      be a serological diagnostic antigen. CONCLUSIONS: The study successfully obtains
      the rROP38 of T. gondii with good reactogenicity.

PMID- 29469493
TI  - [Epidemic situation of malaria and progress of malaria elimination in Nantong
      City from 2008 to 2014].
AB  - OBJECTIVE: To analyze the epidemic status and progress of malaria elimination in
      Nantong City, so as to provide evidences for adjusting the control measures and
      guiding the work of malaria elimination. METHODS: The data about the epidemic
      situation of malaria and malaria elimination in Nantong City from 2008 to 2014
      were collected and analyzed by the method of descriptive epidemiology. RESULTS:
      From 2008 to 2014, a total of 305 malaria cases were reported in Nantong City,
      with an annual average incidence of 0.57/100 000. Among all the cases, 26 (8.52%)
      were local tertian malaria cases and 279 (91.48%) were imported cases; 276 cases
      (90.49%) were male and most of them were young adults, and those aged in 20-59
      accounted for 91.48% (279/305). There were cases reported in each month, with no
      obvious seasonality. The imported cases were mainly distributed in Hai'an County
      (80 cases), Haimen City (71 cases) and Tongzhou District (41 cases), and the
      total percentage of them was 68.82% among all the imported malaria cases in
      Nantong City. There were no local malaria cases reported in Nantong City since
      2011. Qidong City, Rudong County, Chongchuan District, Development Zone and
      Gangzha District have reached the criteria of malaria elimination in Jiangsu
      Province. CONCLUSIONS: From 2008 to 2014, the malaria cases in Nantong City are
      mainly imported cases, the number of local cases has decreased significantly, and
      there has been no local infected cases reported in the continuous 4 years of 2011
      2014. Totally 5 counties (cities, districts) among the 9 have reached the
      criteria of malaria elimination in Jiangsu City. In the future, the control of
      imported malaria should still be strengthened, and the work of malaria
      elimination should still be promoted.

PMID- 29469492
TI  - [Investigation on soil - transmitted nematode infections in national surveillance
      sites in Jiangsu Province from 2006 to 2015].
AB  - OBJECTIVE: To understand the status of soil-transmitted nematode infections in
      rural residents so as to provide the evidence for formulating the guidance for
      prevention and control of the diseases. METHODS: The national surveillance sites
      of soil-transmitted nematode infections were established in Shuyang County,
      Suqian City, Jiangsu Province from 2006 to 2015. At least 1 000 fecal samples of
      residents aged 3 years or above were collected in every autumn, and the
      intestinal helminth eggs were detected with the Kato-Katz technique and the
      Enterubius vermicularis eggs were detected by the cellophane tape method for
      children aged 3-12 years. The soil samples were collected from vegetable fields,
      lavatories, courtyards and kitchens to examine Ascaris lumbricoides eggs and
      larvae of hookworm. RESULTS: The infection rates of soil-transmitted nematodes in
      residents and E. vermicularis in children reduced from 1.81% (19/1 049) and 4.72%
      (5/106) in 2006 to 0.25% (3/1 180) and 0 (0/263) in 2015, respectively, in the
      surveillance sites. The infection intensity was mild in all the infected cases.
      The soil samples were negative for detecting A. lumbricoides eggs and hookworm
      larvae. CONCLUSIONS: The infection rates of soil-transmitted nematodes in the
      residents and E. vermicularis in the children show a decreasing trend and keep at
      a low level of prevalence in Shuyang County.

PMID- 29469494
TI  - [Malaria epidemiological analysis in Tengchong City from 2010 to 2015].
AB  - OBJECTIVE: To analyze the malaria epidemiological characteristics in Tengchong
      City from 2010 to 2015, so as to provide the evidence for adjusting and
      formulating measures in the elimination stage. METHODS: The malaria data were
      collected and analyzed by using Microsoft Excel 2010 in Tengchong City from 2010
      to 2015. RESULTS: There were 1 408 malaria cases reported in Tengchong City from
      2010 to 2015, including 1 091 cases of Plasmodium vivax infection, 256 cases of
      P. falciparum infection, 5 cases of P. malariae infection, 1 case of Plasmodium
      ovale infection, 1 case of mixed infections, and 54 unclassified cases. Totally 1
      390 imported cases were recorded and 98.06% of them (1 363/1 390) were imported
      from Myanmar. Most of the patients (n = 908) were aged from 21 to 40 years, and
      the male to female ratio was 11.03?1. The highest-risk populations were farmers
      and migrant workers. The most cases were observed in April and June, and at that
      time, most of the floating workers returned. CONCLUSIONS: Imported malaria is
      severe in Tengchong City, and there is a great challenge to malaria elimination.

PMID- 29469495
TI  - [Malaria awareness among residents and students during malaria elimination phase
      in Jinshan District, Shanghai City].
AB  - OBJECTIVE: To understand the awareness status of knowledge on malaria control
      among residents and students, so as to evaluate the effectiveness of health
      education during the elimination phase of malaria in Jinshan District, Shanghai
      City. METHODS: In 2010 and 2014, the stratified sampling and cluster sampling
      methods were taken to selected the investigation sites, including 3 villages, 1
      middle schools, 1 primary school, then the residents above 15 years old and the
      students in the above selected sites were investigated by questionnaires to
      understand their awareness status on malaria control. RESULTS: In 2010, the
      general awareness rates of malaria control knowledge of the study objects were
      74.22%, and those of the residents, middle school student, and primary school
      students were 75.68%, 61.86% and 72.20%, respectively. There was no significant
      difference between the awareness rates of objects with different gender (chi2 =
      1.755, P > 0.05). The rate of the residents was higher than that of the students
      (chi2 = 59.838, P < 0.01). From 2010 to 2014, a serious of health education on
      malaria control was carried out. In 2014, the general awareness rate of knowledge
      on malaria control was 96.03%, and those of the residents, middle school student,
      and primary school students were 92.28%, 98.59% and 99.49%, respectively. The
      awareness rate of the students was higher than that of the residents (chi2 =
      275.794, P < 0.01). CONCLUSIONS: Through the health education and community
      advocacy, the awareness rates of knowledge on malaria control among residents and
      students have improved and met the qualification of malaria elimination in
      Jinshan District.

PMID- 29469496
TI  - [Analysis of surveillance results of schistosomiasis in Hexi reservoir area from
      2012 to 2015].
AB  - OBJECTIVE: To understand the changes of schistosomiasis epidemic situation, so as
      to provide the evidence for formulating schistosomiasis control strategy in the
      Hexi reservoir area. METHODS: From 2012 to 2015, Xinyuan Village, Meishan Town in
      the north entrance of Hexi reservoir was selected as a monitoring site. According
      to the requirements of the monitoring program of schistosomiasis surveillance in
      Zhejiang Province, the Schistosoma japonicum infection was investigated by using
      the serological screening (IHA), and the basic situation of the surveillance site
      was also investigated. RESULTS: From 2012 to 2015, 167 environments (21.68 hm2)
      were surveyed, and 2 slices (0.1 hm2) were found with Oncomelania hupensis
      snails. The detection rate of frames with snails was 0.12%, and the living snail
      density was 0.0192 snails per 0.1 m2. Totally 374 snails were dissected and no
      schistosome infected snails were found. A total of 970 local residents and 8 748
      mobile people were investigated with the serological tests, and no schistosome
      infected people were found. In addition, 3 085 cattle were investigated and no
      infected ones were found. CONCLUSIONS: The schistosomiasis epidemic situation is
      stable in the Hexi reservoir area, but we still should strengthen the monitoring
      of imported source of infection and snail status, and increase the efforts of
      environmental transformation.

PMID- 29469497
TI  - [Malaria endemic situation and comprehensive prevention and control measures in
      Caoxian County].
AB  - OBJECTIVE: To understand the malaria endemic characteristics and control measures
      in Caoxian County, Shandong Province, so as to summarize the experiences of
      malaria elimination. METHODS: The data of malaria endemic situation and control
      measures in Caoxian County from 1953 to 2014 were collected and descriptively
      analyzed, and the control effectiveness was evaluated. RESULTS: The incidence of
      malaria reduced from 13.25% in 1970 to 0.33% in 1983, and no malaria case was
      found in 1986. The goal of basic malaria elimination was achieved. The sporadic
      malaria infections were found from 2006 to 2010, and three imported malaria cases
      were found in Caoxian County from 2011 to 2014. CONCLUSIONS: The effect of
      comprehensive prevention and control measures taken in Caoxian County is
      significant, and the goal of malaria elimination has been reached. The imported
      malaria and secondary cases are future focuses of malaria control work.

PMID- 29469498
TI  - [Prevention and control knowledge of echinococcosis in students in Qinghai
      Province].
AB  - OBJECTIVE: To understand the situation of prevention and control knowledge of
      echinococcosis in students in Qinghai Province, so as to provide an evidence for
      effective prevention and control of echinococcosis. METHODS: The students of
      Grade Four or above were randomly selected with the multi-stage stratified
      cluster sampling method and investigated with the questionnaire about
      echinococcosis in Qinghai Province. RESULTS: Totally 23 600 students were
      selected and surveyed, with the pass rate of 66.0% (15 566 cases). The pass rates
      of the male and female students were 65.1% (7 947 cases) and 66.9% (7 619 cases)
      respectively, and the difference was significant (chi2 = 8.454, P < 0.01). The
      difference of pass rates among different districts of Qinghai Province was
      statistically significant (chi2 = 3 848.619, P < 0.01). CONCLUSIONS: The general
      aware rate of echinococcosis knowledge in students is not high in Qinghai
      Province, and therefore, it is necessary to enhance the health education,
      especially for students in pasturing areas.

PMID- 29469500
TI  - [Acarophenax tribalii found in stored grains].
AB  - OBJECTIVE: To observe and understand the morphology and structure of Acarophenax
      tribalii in order to create a new record of this mite in China. METHODS: The
      stored grain samples (rice and brown rice) were collected from the storage of
      local dwellers, and mites breeding in the products were isolated. Then mite
      samples were prepared and identified as the previous protocols, and the species
      was classified in accordance with Hughes. RESULTS: A. tribalii was detected in
      the grain samples. The light microscopic examination exhibited ovally shaped
      idiosoma of this species, and the abdomen of the male was more inflated than that
      of the female. By general view, the propodosomatal plate appeared triangle-like,
      and its anterior margin was covered by the gnathosoma. Leg I consisted of four
      segments, and its tibia and tarsus healing were fused into a stubby tibiotarsus.
      A tarsulus occurred at the end of leg II, III and IV, with a claw born at each
      leg. CONCLUSIONS: The morphology and structure of A. tribalii are characterized.
      This may lay a basis for following study on this species.

PMID- 29469499
TI  - [Oncomelania hupensis snail distribution in working areas of Yangtze River
      hydrologic agencies located in middle and lower reaches of Yangtze River in
      2016].
AB  - OBJECTIVE: To understand the Oncomelania hupensis snail distribution in the
      working areas of Yangtze River hydrologic agencies located in the middle and
      lower reaches of the Yangtze River in 2016, so as to provide the evidence for
      assessing the risk of schistosome infection of hydrological workers and
      establishing the control strategies. METHODS: The suspicious environments with O.
      hupensis snails in the above working areas were selected as study areas, and the
      snail situation was surveyed by the system sampling method combined with the
      environmental sampling method. The survey data were collected and analyzed
      statistically. RESULTS: Totally 19 working areas from 17 hydrological agencies
      were selected as the investigation sites, among which, 10 working areas from 9
      agencies were found with O. hupensis snail distribution. The constituent ratio of
      the areas with snails reached to 38.81% of the investigation areas, the
      occurrence rate of frames with snails was 3.08%, and the average density of
      living snails was 0.07 /0.1 m2. By comparison, the average density of living
      snails and occurrence rate of frames with snails in hydrological agencies under
      the jurisdiction of the Middle Reaches Administrative Bureau were the most
      serious among three administrative bureaus of the Yangtze River Water Resources
      Commission. CONCLUSIONS: There are various degrees of O. hupensis breeding in the
      working areas of hydrological agencies located in the middle and lower reaches of
      the Yangtze River, and the hydrological workers are facing with the risk of
      schistosome infection.

PMID- 29469501
TI  - [Size changes of erythrocytes infected with Plasmodium malariae in thin
      peripheral blood smears].
AB  - OBJECTIVE: To explore the size changes of erythrocytes infected with Plasmodium
      malariae, so as to improve the basic-level experimenters' microscopy capabilities
      for P. malariae identification in thin blood smears. METHODS: The microscopic
      features of erythrocytes infected with P. malariae in thin peripheral blood
      smears were observed, and a microscope image processing software was used to
      measure and analyze the diameter changes of the erythrocytes infected with P.
      malariae. RESULTS: The diameter of erythrocytes infected with P. malariae
      decreased significantly compared with that of the normal erythrocytes. The three
      parameters in this study: the diameter of erythrocytes, the value of diameter
      variation, and the ratio of diameter variation varied at different developmental
      stages of P. malariae, and the differences were statistically significant (all P
      < 0.01). The variances of the three parameters grouped by different cases or
      different developmental stages in different cases were analyzed, all showing
      statistically significant differences (all P< 0.01). CONCLUSIONS: All the
      developmental stages of P. malariae will cause the decrease of the diameters of
      infected erythrocytes in peripheral blood smears, but the influence on the
      diameter of erythrocytes, value of diameter variation, and ratio of diameter
      variation varies at different developmental stages in different cases.

PMID- 29469502
TI  - [Assessment and authentication of malaria elimination in Changzhou City].
AB  - OBJECTIVE: To analyze the results of assessment and authentication of malaria
      elimination of 7 county-level cities and districts in Changzhou City, Jiangsu
      Province, and explore the suitable monitoring methods for malaria after the
      elimination in this region, so as to provide the evidence for formulating and
      adjusting the malaria elimination strategies and measures. METHODS: The data from
      the network reports of malaria epidemic situation, blood examinations of febrile
      patients, epidemiological questionnaires of malaria cases, investigation of
      epidemic focuses and disposal tables were collected and analyzed in Changzhou
      City from 2009 to 2014. The clinicians were assessed with the closed-book written
      examinations for their ability of the diagnosis and treatment of malaria. The
      inspection personnel were assessed by the microscopical examinations of
      Plasmodium. Totally 30 negative blood slides were reviewed. In the natural
      village where the last local case of malaria was located, 200 blood filter papers
      were collected for gene detection of Plasmodium. RESULTS: From 2009 to 2014, 145
      malaria cases were reported in Changzhou City. Totally 170 638 febrile patients
      received blood detections for malaria, of which 137 cases were positive and the
      positive rate was 0.08%. The majority of malaria cases were imported except 8
      local malaria infection cases in 2009 and 2 local malaria infection cases in
      2010. Four of seven county-level cities (districts) gained an average score of 20
      points on the microscopical examinations of Plasmodium. Liyang City got a minimum
      average score of 18.8 points. In capacity assessment of malaria diagnosis and
      treatment, Liyang City gained the highest average score of 19.8 points, and
      Qishuyan District got the lowest average score of 18.0 points. The malaria
      elimination assessment scores of the 7 county-level cities (districts) were all
      above 93 points. Four county-level cities (districts) (Xinbei District, Wujin
      District, Liyang City, and Jintan City) carried out the active case detections. A
      total of 731 cases were detected and the results were all negative. Liyang City
      in 2012, Zhonglou District and Jintan City in 2013, Tianning District, Qishuyan
      District, Xinbei District and Wujin District in 2014, passed the malaria
      elimination assessment at county (district) level, respectively. CONCLUSIONS: All
      the 7 county-level cities (districts) of Changzhou City have passed the malaria
      elimination assessment at a high score. After the malaria elimination, the
      monitoring should continue to consolidate the achievements.

PMID- 29469503
TI  - [Management strategy and technology of medical assistance to advanced
      schistosomiasis patients in Hunan Province].
AB  - The medical assistance to advanced schistosomiasis patients established by the
      Chinese government is a major public facility for patients with advanced
      schistosomiasis. Since the medical assistance to advance schistosomiasis patients
      in Hunan Province started ten years ago, a set of mature and operable programs
      with whole program management and related technologies has been developed. The
      author investigated the data on medical assistance to advanced schistosomiasis
      patients in Hunan Province during the last 10 years (from 2006 to 2015)
      retrospectively, and found that the program had high therapeutic effect and high
      satisfaction degree of both patients and the society. In order to improve the
      management of the medical assistance to advanced schistosomiasis patients and
      share our experiences of the whole program management and related technologies
      with the colleagues of other provinces, this paper mainly illustrates the
      experiences of the program, as well as the existing problems and related
      strategies.

PMID- 29469504
TI  - [Observation on serum gamma-glutamyl transpeptidase levels of patients with
      subclinical schistosomiasis before and after pathogen treatment].
AB  - OBJECTIVE: To observe the changes of serum gamma-glutamyl transpeptidase (GGT)
      levels before and after the pathogen treatment in patients with subclinical
      schistosomiasis, and explore its clinical value in the diagnosis and treatment of
      subclinical schistosomiasis. METHODS: Totally 109 patients with subclinical
      schistosomiasis, who were found in the endemic investigation of schistosomiasis
      in Ezhou City, were selected as the investigation subjects, and then they were
      treated with praziquantel. The serum GGT levels of the subjects before and after
      the treatment were detected and compared. RESULTS: Before the treatment, the
      average value of the GGT levels of the 109 patients was (48.1 +/- 45.9) IU/L,
      among which, the GGT levels of 69 cases (63.3%) were normal, and the levels of 40
      cases (36.7%) were increased. After the treatment, the average GGT level of the
      patients was (32.1 +/- 23.4) IU/L, which decreased by 33.3% comparing with that
      before the treatment, and the difference had a statistical significance (U=2.17,
      P = 0.01). The GGT levels of 65 patients decreased in different degrees. Among
      the 40 patients whose GGT levels had increased before the treatment, the GGT
      levels of 31 ones returned to the normal. CONCLUSIONS: The GGT level detection
      can accurately reflect the liver function in the patients with subclinical
      schistosomiasis, and also it has certain clinical application value to judge the
      liver function damage and recovery of the patients before and after the pathogen
      treatment.

PMID- 29469505
TI  - [Surveillance of imported schistosomiasis in non-endemic areas in Changshu City
      from 2006 to 2015].
AB  - OBJECTIVE: To understand the situation of imported schistosomiasis in non-endemic
      areas along the Yangtze River in Changshu City, so as to provide the evidence for
      formulating and adjusting control measures. METHODS: The data of Oncomelania
      hupensis snails and schistosomiasis patients in Changshu City from 2006 to 2015
      were collected and analyzed. RESULTS: Totally 1 650 residents of Changshu City
      were tested by serum tests from 2006 to 2015, and 35 cases were positive, with a
      positive rate of 2.12%. No positive cases were found in etiological tests. No O.
      hupensis snails were found. CONCLUSIONS: No imported schistosomiasis cases are
      found in the areas along the Yangtze River in Changshu City, but the infection
      source is still possible to be imported, and the surveillance work should be
      strengthened.

PMID- 29469506
TI  - [Effect of wild feces detection in Oncomelania hupensis environments on
      surveillance of infection source of schistosomiasis].
AB  - OBJECTIVE: To evaluate the effect of wild feces detection in Oncomelania hupensis
      environments on the surveillance of infection source of schistosomiasis, and find
      the weakness in schistosomiasis control in Hubei Province, so as to put forward
      the targeted strategies and measures. METHODS: Four environments with O. hupensis
      snails in endemic areas of Hubei Provinces, where human and livestock often
      haunted, were selected according to the river systems, namely the Juzhanghe River
      beach in Jingzhou City, Changjiang River beach in Jiayu County, Hanbei River
      beach in Tianmen City, and Changshou River beach in Zhongxiang City, then the
      snail survey and wild feces detection were implemented in the selected
      environments. RESULTS: There were O. hupensis snails, livestock, wild feces of
      cattle or sheep as well as positive cattle feces found in all the 4 environments,
      and the positive rate of schistosome miracidium incubation was 47.62%.
      CONCLUSIONS: The schistosome miracidium positive rate of wild feces of cattle is
      high in the environments with snails in endemic areas of Hubei Province, which
      has high risk for schistosomiasis transmission.

PMID- 29469507
TI  - [Examination and evaluation on malaria elimination in Baise City].
AB  - OBJECTIVE: To analyze the assessment results and summary the work experience of
      malaria elimination in Baise City. METHODS: According to The malaria elimination
      evaluation schemes of Guangxi (2014 edition), the examination and evaluation of
      malaria elimination were carried out and all the results were analyzed in 12
      counties (county-level city or district) of Baise City from 2014 to 2015.
      RESULTS: Since 2009, there were no local malaria cases and imported secondary
      cases in Baise City for the 6 consecutive years, and the detailed data were
      collected and the self-assessment reports of malaria elimination were written in
      all the counties. There was no omission or delay of malaria case reports in the
      12 counties. The highest score of the examination and evaluation was 96.58
      points, the lowest was 90.76 points, and the average was 93.77 points. The
      biggest impact on the evaluation scores was "on-site examination". CONCLUSIONS:
      All the 12 counties (county-level city or district) of Baise City have passed the
      municipal examination and evaluation of malaria elimination, and the key of next
      work is malaria monitoring, timely finding and treating the imported malaria
      patients, and to guarantee no imported secondary cases.

PMID- 29469508
TI  - [Role of goat in transmission of schistosomiasis japonica IV Goat breeding in
      endemic regions and role of goat in schistosomiasis transmission].
AB  - This review describes the major species, number, breeding pattern, ratio of
      fenced to freely grazed goat, susceptibility to Schistosoma japonicum, pattern of
      S. japonicum infection, infection rate, intensity of infection, fecal
      contamination of goat that were bred in 5 marshland and lake provinces of Hunan,
      Hubei, Jiangxi, Anhui and Jiangsu, and two mountainous provinces of Yunnan and
      Sichuan, and demonstrates the associations of infected goat distribution with the
      distribution of infected Oncomelania hupensis snails and humans. Considering the
      huge number of goat which were predominantly grazed freely in marshland and lake
      endemic regions of China, the high infection rate, numerous environmental
      pollution by goat feces, as well as the close correlation between the infected
      goat distribution and infected snail distribution, goat is considered as a major
      infectious source for schistosomiasis japonica in China, and to play a critical
      role in the transmission of the disease. Since the control of schistosomiasis in
      animals is critical to schistosomiasis interruption and elimination, it is
      suggested that the integrated management of goat schistosomiasis should be
      included in the national schistosomiasis control program of China.

PMID- 29469509
TI  - [A domestic cat infected with a large number of Clonorchis sinensis].
AB  - Adult Clonorchis sinensis not only occurs in human hepatic duct, but also in the
      liver, gallbladder and bile ducts of animals, including dogs and cats, thus
      causing clonorchiasis-one of important parasitic zoonoses. In present study, we
      dissected a domestic cat in which a total of 736 pieces of trematodes, identified
      as Clonorchis sinensis, were detected in the liver and cholecyst. The findings
      indicate that Clonorchis sinensis may be endemic in domestic animals in Wuhu
      area, and observe our awareness in prevention of the parasites in house pets.

PMID- 29469510
TI  - [Challenges and countermeasures for water conservancy combined with
      schistosomiasis prevention and control in China in new era].
AB  - The spread of schistosomiasis seriously threaten the health of people and hinder
      the economic and social development in China. The water conservancy combined with
      schistosomiasis prevention and control effectively controlled the spread of
      schistosomiasis by controlling the spread of Oncomelania hupensis, the only
      intermediate host of Schistosoma japonicum. This paper reviews the evolution of
      the strategy of schistosomiasis prevention and control in China and points out
      the historical role of water conservancy combined with schistosomiasis prevention
      and control. Furthermore, this article analyzes the problems and challenges of
      water conservancy combined with schistosomiasis prevention and control in the new
      period. In response to the challenges, the new strategy of water conservancy
      combined with schistosomiasis prevention and control is put forward, including:
      developing the research of the new strategy of water conservancy combined with
      schistosomiasis prevention and control, enhancing the research of water
      conservancy technology combined with schistosomiasis prevention and control,
      improving the efficiency and applicability of water conservancy projects combined
      with schistosomiasis prevention and control, strengthening the guidance of water
      conservancy technology combined with schistosomiasis prevention and control, and
      perfecting the evaluation system.

PMID- 29469511
TI  - [Challenges and countermeasures of forestry schistosomiasis control programs in
      ecological priority of Yangtze River economic belt development].
AB  - Relevant projects carried out within the Yangtze River economic belt on the
      impact of schistosomiasis epidemic and transmission are important issues for
      "ecological priority" in the process of implementing the strategy. The key
      problems of schistosomiasis epidemic risk, epidemic happening repeatedly,
      difficulty of rehabilitating Oncomelania hupensis snail control and
      schistosomiasis prevention forest, lag of evaluation system and platform
      construction, lack of basic research, et al. were analyzed in the Yangtze River
      economic belt taking "ecological priority" as the basis in this paper. Then
      corresponding countermeasures to these challenges were put forward so as to
      provide the reference for the national forestry schistosomiasis control programs,
      which include: execution of the comprehensive prevention and control strategy,
      scheming of the new round of forestry schistosomiasis control programs,
      strengthening schistosomiasis prevention and control, promoting productivity in
      existing forestry to consolidate and improve the achievements of previous
      forestry schistosomiasis control programs, and promoting the intensity of
      technological innovation to improve the technological level of forestry
      schistosomiasis control programs.

PMID- 29469512
TI  - [Value and evaluation on multidisciplinary treatment of advanced
      schistosomiasis].
AB  - Advanced schistosomiasis, encompassing a wide range of pathologic entities and
      multi-complications, poses a serious threat on the patients' health. Through
      comprehensive analysis and evaluation on related aspects regarding clinical
      classification, main methods of auxiliary examination and treatment (including
      types of surgical procedure) of advanced schistosomiasis, we think that the
      individual based multidisciplinary comprehensive treatment according to varying
      conditions of patients is the most optimal treatment mode of advanced
      schistosomiasis. It is further proposed that multidisciplinary collaborative
      diagnosis and treatment system should be undoubtedly established,
      multidisciplinary case discussions be regularly organized, and treatment expert
      teams be stably formed, in order to significantly improve the level of diagnosis
      and treatment of advanced schistosomiasis, so as to reduce the misdiagnosis and
      improve the therapeutic effect in advanced schistosomiasis control.

PMID- 29469513
TI  - [Surveillance of schistosomiasis in People's Republic of China in 2015].
AB  - OBJECTIVE: To analyze the investigation data of the national schistosomiasis
      surveillance sites in 2015, so as to provide scientific evidences for
      schistosomiasis control, elimination and surveillance. METHODS: According to
      National Schistosomiasis Surveillance Programme (version 2014), 457 surveillance
      sites were selected, and the investigation data in residents, floating
      population, domestic animals and Oncomelania hupensis snails were collected and
      analyzed from four types of endemic counties. RESULTS: A total of 4 468
      seropositive cases were detected from 133 350 residents, among which 4 457
      residents with seropositive results received the etiological tests, and 71 of
      them were identified with positive results. Most of them were fishermen and
      farmers in the middle and old-aged group. The schistosomiasis infection rate was
      0.05% in local population. Totally 977 seropositive cases were examined from 85
      047 migrant individuals, and 16 positive cases were found out from 966
      individuals who took etiological tests, which showed the schistosomiasis
      infection rate was 0.02% in floating population. Imported cases were found among
      floating people in four provinces, namely Zhejiang, Hunan, Hubei and Anhui
      provinces. No acute schistosomiasis cases were reported. A total of 13 406 head
      of cattle received examinations and only 5 were determined as stool positives.
      The cattle infection rate was 0.04%. The snail survey covered an area of 22
      295.13 hm2 and snails were found in an area of 7 426.63 hm2, including 3.47 hm2
      newly detected area with snails. No schistosome-infected snails were found.
      CONCLUSIONS: Based on the collected data from 457 national schistosomiasis
      surveillance sites of China, the Schistosoma japonicum infection rate is 0.05% in
      local population which maintains a stably descending trend. In floating
      population, there are imported schistosome-in-fected persons. Cattle are still a
      vulnerable species infected with schistosome. Although no infected snails are
      found, snails are widely distributed in endemic areas. Some provinces detect
      areas with snails for the first time or the reproduction of snails. The staff in
      endemic provinces should carry out the surveillance work according to National
      Schistosomiasis Surveillance Programme (version 2014) to improve the surveillance
      system, and enhance the sensibility and effectiveness of surveillance work.

PMID- 29469514
TI  - [Analysis of characteristics of medical assistance to advanced schistosomiasis
      patients in Hunan Province, 2015].
AB  - OBJECTIVE: To understand the current distribution and characteristics of advanced
      schistosomiasis patients who accepted medical assistance in Hunan Province in
      2015, so as to provide the evidence for perfecting the policy and measures of the
      medical assistance to advanced schistosomiasis patients. METHODS: The patients
      who had been diagnosed as advanced schistosomiasis were verified and confirmed
      according to the standard of the medical assistance to advanced schistosomiasis
      patients in Hunan Province in 2015. The epidemiological survey was conducted to
      investigate the demographic characteristics, history of diagnosis and treatment,
      and medical assistance to these persons. RESULTS: There were 3 850 advanced
      schistosomiasis patients who accepted the medical assistance in Hunan Province in
      2015, and among them, 2 664 patients were male (69.19%), and 1 186 were female
      (30.81%). Most of them (92.82%) came from the main schistosomiasis endemic areas,
      such as Yueyang, Changde and Yiyang. There were 2 369 cases of ascites (61.53%),
      1 466 cases of splenomegaly (38.08%), 15 cases of colon proliferation and dwarf
      (0.39%). The mean age of advanced schistosomiasis patients who accepted the
      medical assistance was (62.94 +/- 11.67) years old, with 64.31% of them being
      more than 60 years old. The age of initial diagnosis of advanced schistosomiasis
      was (53.85 +/- 21.32) years old, and it was concentrated in 40-60 years old
      (68.57%). The mean duration of advanced schistosomiasis was (9.58 +/- 10.06)
      years, and it was mainly distributed in 10 years (75.95%). The mean duration from
      initial diagnosis of schistosomiasis to advanced schistosomiasis was (22.33 +/-
      14.20) years. The priority of the medical assistance to advanced schistosomiasis
      patients was given to the county hospitals (76.57%); and the effective rate of
      assistance was 94.46%. Totally 86.57% of the patients with advanced
      schistosomiasis got the medical insurance (rural cooperative medical care, urban
      medical care, etc.). CONCLUSIONS: The burden of the medical assistance to
      advanced schistosomiasis patients is still heavy because of many patients and low
      cure rate in Hunan Province. The ascites patients and high age patients should be
      the important objects of the medical assistance.

PMID- 29469515
TI  - [Application of degree of portal systemic shunting in assessing upper
      gastrointestinal bleeding in patients with schistosomiasis cirrhosis].
AB  - OBJECTIVE: To discuss the application of the degree of portal systemic shunting
      in assessing the upper gastrointestinal bleeding in patients with hepatic
      schistosomiasis. METHODS: Thirty-three patients with upper gastrointestinal
      bleeding caused by hepatic schistosomiasis (a bleeding group) and 29
      schistosomiasis cirrhosis patients without bleeding (a non-bleeding group) were
      enrolled as investigation subjects in Jinshan Hospital. The subjects were scanned
      by the 128 abdominal slice spiral CT. The portal systemic shunting vessels were
      reconstructed by using thin slab maximum intensity projection (TSMIP) and
      multiplanar reconstruction (MPR). The degrees of the shunting vessels of the
      subjects were evaluated and compared, and the relationship between upper
      gastrointestinal bleeding and the degree of the shunting was analyzed. RESULTS:
      In the bleeding group, the occurrence rates of the shunting vessels were found as
      follows: 86.4% in left gastric varices, 68.2% in short gastric varices, 50.0% in
      esophageal varices, 50.0% in para-esophageal varices, 37.9% in gastric varices,
      69.7% in gastric-renal varices, 51.5% in spleen-renal varices, 25.8% in abdominal
      wall varices, 15.2% in omentum varices, 63.6% in para-splenic varices, 34.8% in
      umbilical varices, 40.9% in retroperitoneal-paravertebral varices, and 36.4% in
      mesenteric varices. In the bleeding group, the occurrence rates and the degree of
      shunt were significantly higher than those in the non-bleeding group in
      esophageal varices, esophageal vein, left gastric vein and gastric varices (all P
      < 0.05). CONCLUSIONS: CT portal vein reconstruction can accurately display the
      location, degree and walking of all kinds of shunting vessels. Esophageal
      varices, esophageal vein, left gastric vein and gastric varices can accurately
      predict the risk of upper gastrointestinal bleeding in patients with hepatic
      schistosomiasis. The patents with higher degree of the shunting vessels have a
      higher risk of gastrointestinal bleeding.

PMID- 29469516
TI  - [Practice of engineering management and its effect on schistosomiasis control in
      Hankou marshland, Wuhan City].
AB  - OBJECTIVE: To investigate the Oncomelania hupensis snail control effect of
      schistosomiasis control engineering in marshland within Wuhan City. METHODS: The
      engineering measures including surface barrier removal, molluscicide, flatting
      surface, topsoil stripping, topsoil covering and ditch renovation were applied to
      transform Hankou marshland. Then the corresponding technical parameters of
      engineering measures were put forward. The situation of snails was analyzed
      before and after the transform project. RESULTS: The total length and area of the
      project were 6 015 m and 87.21 hm2, respectively, including 17.44 hm2 of topsoil
      landfill, 52.08 hm2 of topsoil covering and 23 new ditches. After the
      transformation, the average length of the new groove, the groove top width,
      groove depth, height difference, and the average values of slopes and ditch
      bottom slope were all increased, while the average values of the width and height
      of the ditch were decreased. At the same time, the marshland beach surface had a
      new slope that the embankment was higher than the river and no living O. hupensis
      snails were found then. CONCLUSIONS: The snail breeding environment in Hankou
      marshland has been effectively changed by the project. However, the constant
      monitoring and engineering management are still needed to consolidate the effect.

PMID- 29469517
TI  - [Distribution features of wild feces in schistosomiasis endemic areas in
      Jiangling County, Hubei Province].
AB  - OBJECTIVE: To understand the spatial distribution characteristics of wild feces
      in schistosomiasis endemic areas of Jiangling County, Hubei Province and further
      explore the source of infection efficiently, so as to provide the evidence for
      the development of corresponding monitoring and response technology. METHODS: In
      2011, the fresh wild feces were investigated every two months in the selected 15
      villages by the severity of historical endemic in Jiangling County. The
      schistosome miracidium hatching method was used to test the schistosome infection
      of the wild feces. The descriptive analysis and spatial analysis were used for
      the description of the spatial distribution of the wild feces. RESULTS: Totally
      701 wild feces samples were collected with the average density of 0.055 6/100 m2,
      and the positive rate of the wild feces was 11.70% (82/701). The results of the
      regression analysis showed a positive spatial correlation between the positive
      rate of wild feces and the rate of human infection, the area with infected
      Oncomelania hupensis and the number of fenced cattle, and the corrected R2 of the
      model was 0.58. CONCLUSIONS: The infection rate of wild feces is positively
      correlated with the rate of human infection, area with infected O. hupensis and
      number of fenced cattle in space in Jiangling County, so the prevention and
      control measures could be conducted according to the spatial distribution of the
      positive wild feces.

PMID- 29469518
TI  - [Study on transcriptome of Oncomelania hupensis before and after Schistosoma
      japonicum invasion I De novo assembly of data by RNA-Seq].
AB  - OBJECTIVE: To produce a comprehensive transcript dataset of Oncomelania hupensis
      before and after Schistosoma japonicum infection, so as to provide experimental
      data for perfecting genetic structural information and excavating related
      molecular markers of O. hupensis infected by S. japonicum. METHODS: O. hupensis
      snails were divided into the following 3 groups: one week after S. japonicum
      miracidium infection, 4 weeks after S. japonicum miracidium infection, and normal
      condition. Million high-quality reads were obtained from the normalized cDNA of
      the pooled samples, which were assembled into transcripts. RESULTS: A total of 63
      686 unigenes were identified and were classified into 4 main categories,
      including general functional prediction (15.36%), signal transduction mechanism
      (11.75%), posttranslational modification (8.89%), and functional unknown
      (12.20%). CONCLUSIONS: The transcriptome information of O. hupensis snail after
      the invasion of S. japonicum shows that several genes are significantly up
      regulated or down regulated expression, and that the availability of
      transcriptome information might provide a strong foundation for further
      understanding the schistosome-snail interaction at the molecular level.

PMID- 29469519
TI  - [Comparative analysis of malaria detection ability of laboratories in Shanghai
      City from 2012 to 2015].
AB  - OBJECTIVE: To compare the application effects of three methods, namely
      microscopic examination, antigen detection (RDT) and nucleic acid test (PCR) in
      malaria detection between municipal and districts/counties centers for disease
      control and prevention in Shanghai, and analyze the malaria detection ability of
      the laboratories in Shanghai. METHODS: The blood smears, whole blood samples,
      case review confirmation records and case data of malaria cases and suspected
      cases in Shanghai from 2012 to 2015 were collected by Shanghai Municipal Center
      for Disease Control and Prevention, and the detection results were analyzed and
      compared. RESULTS: A total of 212 samples with complete data were submitted by
      all districts (counties) in Shanghai from 2012 to 2015, the samples submitted by
      Jinshan Districts were the most (41.98%), and among the first diagnosis
      hospitals, those submitted by the tertiary hospitals were the most (82.07%). The
      submitted samples in the whole year were increased gradually from January to
      October. All the 212 samples were detected by three methods (the microscopic
      examination, RDT and PCR) in the laboratory of Shanghai Municipal Center for
      Disease Control and Prevention, and 167 were tested and confirmed comprehensively
      as positives, accounting for 78.77%, and 45 were confirmed as negatives,
      accounting for 21.23%. The samples were detected by the method of microscopy and
      domestic RDT in the laboratories of the centers for disease control and
      prevention at district/county level, totally 153 were tested as positives,
      accounting for 72.17%, 41 were unclassified, accounting for 19.34%, 53 were
      negative, accounting for 25.00%, and 6 were undetected, accounting for 2.83%. The
      coincidence of microscopic examination between the report hospitals and the
      centers for disease control and prevention at district/county level was 78.16%,
      and the coincidence between centers for disease control and prevention at
      district/county level and municipal level was 93.20%. The utilization rate of RDT
      in the laboratory of district/county level was 73.58%. The coincidence of RDT
      tests between those domestic and imported was 93.59%. Compared with the detection
      results by municipal center for disease control and prevention, 37 samples were
      misjudged by the laboratories of district/county level. Almost all (99.37%) of
      the confirmed malaria cases were imported overseas, including Africa (85.44%),
      Asia (13.92%) and America (0.63%). CONCLUSIONS: The surveillance after malaria
      elimination in Shanghai should be carried out by combining with different
      detection methods and resource integration.

PMID- 29469520
TI  - [Epidemiological analysis and control strategy discussion for overseas imported
      malaria cases reported in Chongqing City from 2011 to 2015].
AB  - OBJECTIVE: To analyze the epidemiological characteristics of overseas imported
      malaria reported in Chongqing City from 2011 to 2015, so as to provide the
      evidence for improving the imported malaria control strategies. METHODS: The
      epidemiological data of overseas imported malaria cases were collected and
      analyzed descriptively for the species, original countries, diagnosis and
      treatment in Chongqing City from 2011 to 2015. RESULTS: A total of 148 overseas
      imported malaria cases were reported in Chongqing City from 2011 to 2015, in
      which 96 (65.54%) cases were falciparum malaria, and 37 (24.32%) cases were vivax
      malaria; 125 (84.46%) cases were infected in Africa, and the rest of 23 (15.54%)
      cases were infected in Southeast Asia. Most of the patients were 30 to 50 years
      old male workmen, and the ratio of male to female was 11.42:1. There was no
      obvious seasonal distribution among the reported timelines of the cases; however,
      there were two small peaks from June to August and from January to February. The
      median interval time of imported malaria cases from malaria onset to see a doctor
      was 1 day and from seeing the doctor to get malaria diagnosis was 2 days. The
      patients' first selected institutions were county medical institutions (50 cases,
      33.78%), then provincial medical institutions (36 cases, 24.325%) and private
      doctors (20 cases, 13.51%), and only 79 (53.38%) patients got malaria diagnoses
      in their first selected institutions. The standard treatment were provided to 142
      (95.54%) cases. There were 43 (29.05%) patients had serious complications and
      three patients were dead. CONCLUSIONS: It is very important to enhance the multi
      sector's collaboration to establish the collaborative investigation mechanism for
      screening malaria patients, and strengthen malaria health education for overseas
      workers and training courses in primary care medical institutions.

PMID- 29469521
TI  - [Anti-tumor effect of Plasmodium yoelii infection on melanoma in mice].
AB  - OBJECTIVE: To explore the anti-tumor effect of 17XL strains of Plasmodium yoelii
      (P.y) infection on melanoma in mice. METHODS: B16F10 tumor cells were axillarilly
      injected into the right flank of 20 C57BL/6 mice to establish tumor-bearing mouse
      models. The next day, the mice were randomly divided into a P.y infection group
      and control group, 10 mice each group. Each mouse of the P.y infection group was
      intraperitoneally injected with 1*106 red blood cells including 20% P.y infection
      red blood cells, and each one of the control group were intraperitoneally
      injected with 1*106 normal red blood cells of C57BL/6 mice. The time of tumor
      formation of the mice in the two groups was observed and the tumor volumes were
      measured. RESULTS: The time of tumor formation in the P.y infection group[ (11.30
      +/- 0.21) d]was significantly later than that in the control group [ (10.40 +/-
      0.22) d] (P < 0.05). From the tumors could be accurately measured to the study
      end point, both the tumors of mice in the two groups were growing, and the tumor
      volumes of mice in the P.y infection group were significantly less than those in
      the control group at each time point (all P < 0.05). The growth rate of tumors in
      the P.y infection group [ (71.10 +/- 6.29) mm3/d] was significantly slower than
      that in the control group [ (302.80 +/- 49.94) mm3/d] (P < 0.05), and the growth
      rates of tumors everyday in the P.y infection group were significantly slower
      than those in the control group (all P < 0.05). CONCLUSIONS: The P.y infection
      can delay the occurrence of tumor and inhibit the growth of melanoma.

PMID- 29469522
TI  - [In vitro pro - angiogenic activity of Echinococcus granulosus hydatid cysts from
      experimentally infected mice].
AB  - OBJECTIVE: To preliminarily study the pro-angiogenic activity of Echinococcus
      granulosus hydatid cysts against human umbilical vein endothelial cells in vitro
      and the transcriptional level of potential pro-angiogenic factors. METHODS: The
      hydatid cysts and protoscolex derived from experimentally infected mice were
      collected and cultured in vitro, then the human umbilical vein endothelial cells
      were stimulated by the supernatant and cyst fluid respectively, and the
      angiogenesis was observed and analyzed through a microscope and the angiogenesis
      mode of the software NIH Image J. Meanwhile, the mouse homologous proteins of
      matrix metalloproteinase-9 (MMP-9) and high mobility group box B1 (HMGB1) were
      identified in E. granulosus genome through sequence alignment, and their
      transcriptional levels in the cyst wall and protoscolex were analyzed. RESULTS:
      The culture supernatant of hydatid cysts significantly promoted human umbilical
      vein endothelial cells into tubes (F = 73.03, P < 0.001), the transcriptions of
      MMP-9 and HMGB1 were detected in the cyst wall and protoscolex, and the
      transcriptional level of MMP-9 was higher in protoscolex (t = -11.65, P < 0.001),
      while the level of HMGB1 was higher in hydatid cysts (t = 6.43, P = 0.003).
      CONCLUSIONS: Some parasite-derived pro-angiogenic molecules may exist in the
      supernatant of E. granulosus hydatid cysts, while further researches are required
      into their exact mechanisms.

PMID- 29469523
TI  - [Evaluation on application of China Disease Prevention and Control Information
      System of Hydatid Disease II System integration and simulation tests].
AB  - OBJECTIVE: To report the integrated progress of the hydatid disease information
      management system, and to provide the reference for further system improvements
      by analysis of results on simulation test feedback. METHODS: The work of
      institutional code matching by collecting fundamental and integrated information
      of the system in epidemic areas of hydatid disease was carried out, and
      professional control agencies were selected to carry out the simulation test.
      RESULTS: The results of agencies code matching at stage indicated the average
      completion rate was 94.30% on administrative agencies, 69.94% on registered
      professional agencies and 56.40% on professional institutions matching related to
      hydatid disease prevention and control implements in seven provinces (autonomous
      regions) and Xinjiang Production and Construction Corps. Meanwhile, the response
      rate of open-ended proposals was 93.33% on fifteen feedbacks, and the statistics
      showed 21.43% believed the system was low fluency, 64.29% considered the system
      was inconvenience for data inputs and 42.86% considered it would be improved on
      system statistics functions, of which 27.78% were provincial users, 22.22% were
      the city users and 50.00% were the county users. CONCLUSIONS: The hydatid disease
      prevention information management system meets the fundamental needs of the
      majority agencies in hyperendemic areas of echinococcosis, it needs to develop
      the further test with more agencies joining after the work of the institutional
      code matching completion and the system service improvement in the next stage.

PMID- 29469524
TI  - [Genotype analysis of Toxoplasma gondii isolated strains from congenital teras
      and HIV-Toxoplasma co-infected patient in Jiangsu Province].
AB  - OBJECTIVE: To identify the genotype of Toxoplasma gondii isolated strains from a
      congenital teras (KS strain) and an HIV-Toxoplasma co-infected patient in Jiangsu
      Province. METHODS: T. gondii DNA of tachyzoites of a isolate from a congenital
      teras (KS strain) and blood DNA of an HIV-Toxoplasma co-infected patient in
      Jiangsu Province were extracted, and 11 loci were identified for the genotype by
      polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).
      RESULTS: The complete bands were obtained from the congenital teras (KS strain)
      and HIV-Toxoplasma co-infected patient in Jiangsu Province, and identified as T.
      gondii gene type I. CONCLUSIONS: T. gondii gene type I may be the dominant
      genotype strain of T. gondii among the women who have the abnormal pregnant
      outcomes and HIV-Toxoplasma co-infected patients in Jiangsu Province.

PMID- 29469526
TI  - [Density and hydrostatic settling velocity of Biomphalaria straminea].
AB  - OBJECTIVE: To understand the eco-hydraulics characteristics of Biomphalaria
      straminea, the intermediate host of Schistosoma mansoni. METHODS: The drainage
      method and settlement tube method were applied to measure B. straminea's density
      and hydrostatic settling velocity respectively. RESULTS: The density of B.
      straminea was 1.04-1.16 g/cm3, and the average value was 1.08 g/cm3. The
      hydrostatic settling velocity was 2.32-12.92 cm/s. CONCLUSIONS: The eco
      hydraulics characteristics of B. straminea is different from Oncomelania
      hupensis, and more attention should be paid to the hydraulic measures for the
      control of B. straminea.

PMID- 29469525
TI  - [Comparison of three different methods for isolating RNA from Oncomelania
      hupensis].
AB  - OBJECTIVE: To compare the effects of three kinds of Oncomelania hupensis RNA
      extraction methods, namely a modified SDS method, TRIzol reagent method, and CTAB
      method, so as to obtain an economical and efficient method for RNA extraction
      from O. hupensis. METHODS: The modified SDS method, TRIzol reagent method and
      CTAB method were applied to extract the RNA from O. hupensis. A nucleic acid
      protein analyzer was used to measure the concentration and purity of RNA. The
      yields were calculated by the concentration of the products. The purity was
      indicated by A260/A280 and A260/A230. The quality of RNA was inspected by 1%
      agarose gel electrophoresis. The beta-acting gene was selected as the target gene
      for RT-PCR analysis. RESULTS: The RNA yields obtained by using the three kinds of
      extraction methods were significantly different (F = 16 895.85, P < 0.01)
      according to the analysis of variance. The LSD test showed that the yields
      obtained by using the modified SDS method were the highest, and those obtained by
      the CTAB method were the lowest. The purity of RNA extracted by the CTAB method
      was superior to that by the other two methods, and the A260/A280 and A260/A230
      ratios of the CTAB method were in the range from 1.8-2.0 and 2.0-2.2. The
      A260/A230 ratios of the other two methods were both lower than 2.0. The RNA
      extracted by the modified SDS method had the better integrity. The
      electrophoresis results showed that the 28S rRNA band, 18S rRNA band and 5S rRNA
      band were clear, and there was no obvious smear between each band. The RNA
      obtained by the TRIzol reagent method had no 28S rRNA band, and that obtained by
      the CTAB method had no 28S rRNA and 5S rRNA bands. The beta-acting gene of the
      RNA extracted by all the three methods could be amplified by RT-PCR. The costs
      and time-consuming of the modified SDS method were less than those of the other
      two methods. CONCLUSIONS: The modified SDS method is an economic and efficient
      method, and it is suitable for extracting the RNA of O. hupensis, especially for
      large sample preparation.

PMID- 29469527
TI  - [Laelaps echidninus found on skin of Apodemus agrarius in Wuhu area].
AB  - OBJECTIVE: To report the seizure of Laelaps echidninus on the surface of Apodemus
      agrarius in Wuhu area for the first time, which prompts that there may exist the
      spread of the diseases by mites. METHODS: The mites got from the rats poisoned by
      bait were made as the routine slide specimen and then identified with the
      reference of previous literature. RESULTS: The mites seized from Apodemus
      agrarius were 8 female ones totally and identified as Laelaps echidninus.
      CONCLUSIONS: There exsits Laelaps echidninus parasitic on the body of Apodemus
      agrarius in Wuhu area, which should be paid attention to seriously in order to
      prevent the spread of diseases by it.

PMID- 29469528
TI  - [Short - term effects of two kinds of plastic mulch on Oncomelania hupensis snail
      control in irrigation and drainage ditches in Yunnan Province].
AB  - OBJECTIVE: To evaluate and compare the short-term effects of two kinds of plastic
      mulch on Oncomelania hupensis snail control in irrigation and drainage ditches
      with snails in Yunnan Province. METHODS: The irrigation and drainage ditches with
      high density of Oncomelania hupensis snails were chosen as the investigation
      sites, and then 4 groups were set, namely a colorless plastic mulch group, black
      plastic mulch group, colorless plastic mulch with molluscicide group and black
      plastic mulch with molluscicide group. The snail situation of the 4 groups was
      surveyed before the experiment and 7, 14, 21, 30 days after covering plastic
      mulch, and the snail death rates were compared among the 4 groups. Meanwhile, the
      hourly temperatures of soil surface, soil surface under plastic mulch and soil
      layer 5, 15 cm under the surface as well as the weather situation during the
      study period were measured and recorded. RESULTS: The average snail mortality
      rate of the colorless plastic mulch group was only 15.29% that was higher than
      that of the black plastic mulch group (6.56%) (P < 0.01). The average snail
      mortality rates of the colorless and black plastic mulch with molluscicide groups
      were 40.80% and 50.15%, respectively, and there was no statistic difference
      between them (P > 0.05). Both kinds of plastic mulches could raise the
      temperature of the soil surface under plastic mulch and the soil layer below it,
      and the temperature of soil under the mulches increased over the cover time, and
      the average temperature of the soil surface under the black mulch in 30 days was
      higher than that under the colorless mulch. CONCLUSIONS: It is not suitable to
      use plastic mulch only in irrigation and drainage ditches with snails widely in
      Yunnan Province because of its low effect, and if necessary, the molluscicide
      should be added.

PMID- 29469530
TI  - [Percutaneous transsplenic varices embolization in treatment of upper
      gastrointestinal hemorrhage of schistosomiasis cirrhosis].
AB  - OBJECTIVE: To evaluate the application value of percutaneous transsplenic varices
      embolization (PTSVE) in the treatment of upper gastrointestinal hemorrhage in
      patients with schistosomiasis cirrhosis. METHODS: Sixteen schistosomiasis
      cirrhosis patients (12 males and 4 females) with portal hypertension complicated
      with esophageal and upper gastrointestinal hemorrhage were selected as the
      investigation subjects, all the patients had been treated by esophageal vein
      ligation and sclerotherapy, but with bleeding again post-operation. The patients
      were treated by PTSVE under the guidance of X-ray fluoroscopy. The success rate
      of PTSVE and the rate of complications were observed. In addition, the patients
      received PTSVE were reexamined with abdominal CT one month post-operation, and
      the degrees of varices were compared before and after PTSVE. RESULTS: Fourteen
      cases (87.50%) were successfully treated with PTSVE. Two cases (12.50%) failed,
      and one case had an abdominal bleeding 1 week post-operation. The abdominal CT
      showed the degrees of esophageal varices (P < 0.001), esophageal vein (P < 0.001)
      and gastric varices (P < 0.001) were significantly decreased in the patients who
      received PTSVE one month after the operation. CONCLUSIONS: PTSVE is a safe and
      effective method in the treatment of upper gastrointestinal hemorrhage in the
      patients with schistosomiasis cirrhosis. PTSVE is especially suitable for the
      patients with severe liver cirrhosis, significantly bordered liver split, and
      bared main portal vein and even the branches.

PMID- 29469529
TI  - [Investigation on knowledge, attitude, and practice of schistosomiasis prevention
      and control and infection status in Armed Police Forces stationed along Yangtze
      River].
AB  - OBJECTIVE: To understand the status of knowledge, attitude, and practice of
      schistosomiasis prevention and control and infection status in Armed Police
      Forces stationed along the Yangtze River, so as to provide the reference for
      formulating the schistosomiasis prevention and control measures in Armed Police
      Forces. METHODS: A questionnaire survey was conducted in the Armed Police Forces
      along the Yangtze River in Jiangsu Province, and the investigation content
      included social demographic data, schistosomiasis prevention knowledge, attitude
      and behavior. All the subjects were examined for Schistosoma japonicum infection.
      RESULTS: Totally 376 soldiers were investigated in 2 sites. The total passing
      rate of schistosomiasis knowledge was 72.87%. The passing rate among different
      age groups had no significant difference ( chi2 =0.26, P > 0.05). The passing
      rate of soldiers from endemic areas was significantly higher than that of the
      soldiers from non-endemic areas ( chi2 =4.71, P < 0.05). The passing rate of
      officers was significantly higher than that of the soldiers (chi2 = 4.21, P <
      0.05). The passing rate of soldiers with the education levels of junior school,
      high school, college, undergraduate and above increased gradually, with a
      significant difference (chi2 =8.16, P < 0.05). The soldiers with positive
      attitude accounted for 93.88%. Among the water contact behaviors, training
      accounted for 17.55% and participating in the task (such as flood fighting and
      water work) accounted for 86.44%. When launching, the rate of taking protective
      measures was 52.93%. The rate of taking protective measures in the knowledge
      passing group was much higher than that in the knowledge failed group (chi2
      =10.55, P < 0.05). The stool was harmlessly treated in the two camps. Among 376
      soldiers, the positive rate of blood examinations was 0.53%, but the stool
      examinations were all negative. CONCLUSIONS: The overall level of knowledge and
      correct behavior of schistosomiasis prevention in the Armed Police Forces along
      the Yangtze River still should be improved. The better health education and
      behavior intervention are crucial to schistosomiasis prevention in the army.

PMID- 29469531
TI  - [Survey on Toxoplasma gondii infection among key populations in Wuxi City].
AB  - OBJECTIVE: To investigate the prevalence and risk factors of Toxoplasma gondii
      infection among key populations in Wuxi City, Jiangsu Province, so as to provide
      evidences for developing preventive and control interventions for T. gondii
      infection. METHODS: A questionnaire was designed to conduct face-to-face
      interviews to HIV/AIDS carriers/patients, tumor patients, pregnant women and pet
      breeders. The blood samples were collected to test anti-Toxoplasma IgM and IgG
      antibodies by using ELISA method. RESULTS: Totally 404 participants were
      investigated, and 38 were positive in testing T. gondii antibodies (9.4%), and
      among these, 37 (97.4%) were IgG positive and 1 (2.6%) was IgM positive. The
      multivariate logistic regression indicated that age, regularly contacting
      cats/dogs and being HIV positive were associated with the infection of T. gondii
      (OR=2.1, 2.6 and 2.3, all P < 0.05). Breeding pets, being HIV positive and being
      tumor patients were more likely to infect T. gondii than being pregnant (OR =
      1.5, 8.1 and 2.8, all P < 0.05). CONCLUSIONS: The high infection rate of T.
      gondii is observed among key populations in Wuxi City, so that the effective
      measurements should be taken to enhance the intervention among key populations
      including immunocompromised people, pet breeders or people having bad dietary
      habits of eating raw food.

PMID- 29469533
TI  - [Investigation on Demodex infection status and influencing factors in medical
      students in Wuhu City].
AB  - OBJECTIVE: To investigate the Demodex infection status and influencing factors in
      medical students in Wuhu City. METHODS: The mite specimens were collected by the
      cellophane tape method, and the influencing factors were investigated through the
      questionnaires. RESULTS: A total of 316 medical students were surveyed, 117
      students were infected with Demodex mite, and the total infection rate was
      37.03%. There was no significant difference between the male and female in the
      infection rate (chi2 = 0.00, P > 0.05). Of the 117 infected cases, the infection
      rate of simple Demodex folliculorum was 51.28%, the infection rate of simple
      Demodex brevis was 24.79%, and the rate of mixed infections was 23.93%. The rate
      of the mild infection (83.76%) was significantly higher than that of the moderate
      infection (12.82%) and that of the severe infection (3.42%). The infection rate
      in the forehead was the highest (29.41%). Among the students with the oily skin,
      the infection rate of Demodex mite was related to sex. The infection rate of
      simple Demodex brevis in the male (3.70%) was lower than that in the female
      (16.42%) (chi2 = 6.92, P < 0.05), while the rate of the mixed infections in the
      male (17.28%) was higher than that in the female (4.48%) (chi2 = 5.91, P < 0.05).
      The infection rate of facial skin with symptoms (51.80%) was higher than that of
      normal facial skin (33.05%) (chi2 = 9.14, P < 0.01). There was no significant
      difference between the infection rate of Demodex mite and the living habits and
      other factors. CONCLUSIONS: There is some infection of Demodex in the medical
      students. The infection rate of facial skin with symptoms is higher than that of
      the normal facial skin. So we should strengthen the prevention and treatment of
      Demodex infection in medical students.

PMID- 29469532
TI  - [A comparison of knowledge awareness rates and influencing factors of
      clonorchiasis among residents in 4 counties (cities) of Hunan Province].
AB  - OBJECTIVE: To understand the status of knowledge awareness rates and influencing
      factors of clonorchiasis among the residents in 4 counties (cities) of Hunan
      Province, so as to provide the references for formulating the prevention and
      control strategy of clonorchiasis in the province. METHODS: A total of 1 224
      subjects were selected by the multi-stage cluster sampling method and
      investigated with questionnaires and face-to-face interviews. RESULTS: The
      clonorchiasis knowledge awareness rates of the residents were 15.67% in Yongzhou
      City, 9.94% in Yueyang City, 13.25% in Wangcheng County, and 21.96% in Tongdao
      County, respectively. In the whole province, the clonorchiasis knowledge
      awareness rates of the residents were 44.67%, 56.43%, 60.95%, and 42.46% in the
      etiology, clinical manifestations, epidemiological characteristics and daily
      prevention, respectively. The logistic regression showed that the influencing
      factors of clonorchiasis knowledge awareness rates were the daily dining place,
      whether or not having the medical personnel in the family, the degree of
      attention to the relevant news reports, and the history of parasitic diseases.
      CONCLUSIONS: The level of clonorchiasis than that in other areas, but the overall
      level of clonorchiasis knowledge awareness of the residents in Hunan Province is
      not high. Therefore, the relevant authority should strengthen the health
      education in clonorchiasis prevention knowledge including personal daily food
      hygienic knowledge. knowledge awareness rate of the residents in the west
      southern areas of Hunan Province is higher.

PMID- 29469534
TI  - [Development and application of WEB-based information management system for
      chronic schistosomiasis patients].
AB  - To improve the management level of patients' information of schistosomiasis
      control stations in Nanchang City, the B/S three-layer architecture and ASP+SQL
      technology were applied to formulate the WEB-based management system of chronic
      schistosomiasis patients' information, so as to achieve the information sharing
      of chronic schistosomiasis among schistosomiasis control stations.

PMID- 29469535
TI  - [Retrospective analysis of schistosomiasis elimination history in Jingxi City,
      Guangxi Zhuang Autonomous Region].
AB  - OBJECTIVE: To understand the schistosomiasis epidemic and control history in
      Jingxi City, so as to provide the evidence for improving the future work.
      METHODS: The data of schistosomiasis prevention and control work were collected
      and analyzed comprehensively in Jingxi City from 1956-2015. RESULTS: From 1956,
      the schistosomiasis prevention and control work carried out, and in 1985, Jingxi
      City reached the standard of schistosomiasis transmission interrupted and no
      local schistosome infected residents and livestock were found for 36 years. In
      May 2016, the city reached the national standard of Schistosomiasis Elimination
      Assessment Review. The cumulative number of schistosomiasis detection of
      residents was 348 801 person-times, and 10 434 schistosomiasis patients were
      found. The cumulative number of schistosomiasis detection of cattle was 20 674
      head-times, and 590 schistosome infected cattle were found. The cumulative
      schistosomiasis treatment number of residents was 18739 person-times, and 512
      cattle were treated. The cumulative detection area with Oncomelania hupensis was
      65 213.25 hm2, and 353.80 hm2 area with O. hupensis snails was found.
      CONCLUSIONS: Jingxi City has reached the standard of schistosomiasis elimination,
      but there is still recurrence of O. hupensis snails, and the imported infection
      source exists. Therefore, we should strengthen the monitoring of floating
      population.

PMID- 29469536
TI  - [Experience and analysis of excellent works of human parasitology in national
      medical colleges and universities].
AB  - Teaching competition is an effective way for college and university teachers to
      improve their teaching skills. Based on the teaching practice and experience in
      medical parasitology, this paper discusses several key issues in teaching
      competition including topics, teaching designs and teaching methods. It provides
      references for the teachers in department of parasitology of universities and
      colleges to improve the quality of classroom teaching.

PMID- 29469537
TI  - [Schistosomiasis surveillance among migrant population in Haining City in 2015].
AB  - OBJECTIVE: To understand the schistosomiasis epidemic situation among migrant
      population, so as to assess the potential risk of schistosomiasis transmission in
      Haining City. METHODS: Five districts in Haining City were randomly selected to
      investigate the schistosomiasis endemic situation in migrant population from the
      schistosomiasis endemic provinces. RESULTS: Totally 1 207 persons were
      investigated and four positives were found in serological tests, with the
      positive rate of 0.33%, but no patients were found in pathologic tests. The
      positive cases in serological tests were mainly between 31-40 years old, with the
      positive rate of 1.68%, which was higher than that of other age groups (chi2 =
      6.590, P < 0.05). CONCLUSIONS: The schistosomiasis surveillance work in migrant
      population still should be strengthened in Haining City.

PMID- 29469538
TI  - [Analysis of epidemiological characteristics of imported malaria cases in
      Chongqing Municipality in 2015].
AB  - OBJECTIVE: To analyze the laboratory diagnosis results and epidemiological
      characteristics of imported malaria cases in Chongqing Municipality in 2015.
      METHODS: According to the Standard Operating Procedures of Malaria Diagnosis
      Reference Laboratory Manual, all the blood samples collected from the imported
      malaria patients were detected by microscopy, RDT and nest PCR. Meanwhile, the
      epidemiological data of the malaria cases were collected from the Parasitic
      Diseases Information Management System and analyzed. RESULTS: Totally 31 cases of
      imported malaria were reported in Chonqing Municipality in 2015, among which,
      there were 2 vivax malaria cases (6.45%), 23 falciparum malaria cases (74.19%), 5
      ovale malaria cases (16.13%), 1 malariae malaria case (3.22%). For the 5 ovale
      cases, three of them were confirmed as Plasmodium ovale wallikeri infection.
      Among all the cases, 30 cases (96.77%) were from African countries, 1(3.33%) was
      from Southeast Asia. Thirty patients were male, and 1 was female. All the
      patients were aged from 23-61 years. There was no obvious seasonality in the case
      distribution. Both the medians of duration from malaria attack to first visiting
      a doctor and from first visiting a doctor to diagnosis were 2 days. The medical
      care units that the patients first visited were mainly county-level units, while
      those that made the diagnosis were mainly provincial level institutes.
      CONCLUSIONS: All the malaria cases in Chongqing in 2015 are imported, no local
      cases have been found, which suggests that this municipality still maintain the
      malaria elimination state. However, the monitoring and management of imported
      malaria cases as well as the training on malaria control for related medical
      staff still need to be strengthened.

PMID- 29469539
TI  - [Survey of Toxoplasma gondii infection characteristics and its risk factors among
      healthy blood donation population in Shijiazhuang City, Hebei Province].
AB  - OBJECTIVE: To understand the prevalence of Toxoplasma gondii infection and its
      risk factors among healthy blood donation population in Shijiazhuang City, Hebei
      Province, so as to provide the evidence for developing effective prevention and
      control measures. METHODS: A total of 1 630 cases of blood donors in Shijiazhuang
      City were chosen as respondents, and all the respondents were qualified to the
      standard of blood donation. The antibodies to T. gondii were detected by using
      ELISA. The infection rates of T. gondii in blood donation population were
      compared between/among different genders, ages, occupations, education levels,
      and places of residence. The risk factors for Toxoplasma infection were surveyed
      with questionnaires. RESULTS: A total of 1 630 cases of healthy blood donors were
      investigated, and among which 126 cases were positive in the detection of
      antibodies to T. gondii and the positive rate was 7.73%. The positive rates
      between/among the different genders, ages, occupations, and education levels were
      significantly different (chi2 = 4.36, 13.98, 9.71, 7.65, respectively, all P <
      0.05), and the positive rates among different places of residence were not
      significantly different (chi2 = 1.63, P > 0.05). The questionnaire survey showed
      that the T. gondii infection was closely related to keeping pets, outside eating
      frequently, having chafing dish or barbecue, sharing cutting board for cooked and
      uncooked food, and no the habit of washing hands before meals. CONCLUSIONS: The
      infection rate of T. gondii is relatively high among the healthy blood donation
      population in Shijiazhuang region. The cognitive education for T. gondii
      infection and infection monitoring are the keys to avoid the transfusion
      infection.

PMID- 29469540
TI  - [Correlation between hepatic fibrosis and anti - neutrophil cytoplasmic
      antibodies (ANCA) in schistosomiasis patients].
AB  - OBJECTIVE: To investigate the association between hepatic fibrosis and anti
      neutrophil cytoplasmic antibodies (ANCA) in the patients with schistosomiasis.
      METHODS: Totally 145 schistosomiasis patients confirmed by Jingzhou First
      People's Hospital during the period of February 2014 to June 2016 were randomly
      selected as an experimental group, and 100 healthy people during the same period
      were randomly selected as a control group. The serum samples of the two groups
      were collected and the level of ANCA was detected by indirect immunofluorescence,
      and the levels of hyaluronic acid, laminin, procollagen type III, and collagen
      type IV were detected by radioimmunoassay. The levels of the above indexes of the
      two groups were compared. RESULTS: The positive rate of ANCA was 28.96% (42/145)
      in the experimental group and 1.00% (1/100) in the healthy control group, and the
      difference between them was statistically significant (P < 0.05). The levels of
      hyaluronic acid, laminin, procollagen type III and collagen type IV in the
      experimental group were significantly higher than those in the control group, and
      the differences were statistically significant (all P < 0.05), and the
      proportions of those with abnormal levels of hyaluronic acid, laminin,
      procollagen type III and collagen type IV in the experimental group were
      significantly higher than those in the control group, and the differences were
      statistically significant (all P < 0.05). In the experimental group, among the 42
      patients with ANCA positives, the proportions of those with abnormal levels of
      hyaluronic acid and laminin were significantly higher than the proportions of
      those with ANCA negatives, and in the former, the levels of the four indicators
      of liver fibrosis were all higher than the normal values, and the average levels
      of hyaluronic acid and laminin in the patients with ANCA positives were
      significantly higher than those in the patients with ANCA negatives (all P <
      0.05). CONCLUSIONS: The patients with schistosomiasis hepatic fibrosis could be
      positive for the autoimmune antibody ANCA, and ANCA may be associated with the
      autoimmune process of liver fibrosis.

PMID- 29469541
TI  - [Endemic situation of schistosomiasis at national surveillance sites in Nanjing
      City, 2015].
AB  - OBJECTIVE: To understand the dynamic endemic situation of schistosomiasis in
      Nanjing City, 2015, so as to provide evidences for policy-making of
      schistosomiasis control. METHODS: According to The National Scheme of
      Schistosomiasis Surveillance (2014), the endemic situation of schistosomiasis was
      monitored in 11 national surveillance sites in Nanjing. RESULTS: The positive
      rates of serological (IHA) and stool examinations were 2.97% (97/3 269) and 0 for
      local residents, and 0.52% (12/2 298) and 0 for migrant people, respectively. No
      schistosome-infected livestock was found. Totally 147.295 3 hm2 area with
      Oncomelania hupensis snails were found, but no schistosome-infected snails were
      discovered. CONCLUSIONS: The endemic situation of schistosomiasis declines
      greatly in Nanjing City in 2015. However, the control work still should be
      strengthened to consolidate the achievements of schistosomiasis control.

PMID- 29469542
TI  - [Progress and application of immunodiagnostic methods of giardiasis].
AB  - Giardia lamblia is an important intestinal protozoan which can cause diarrhea in
      humans. The detection of Giardia infection is performed through the detection
      methods of pathogen, immunoassay and molecular biology. Currently, the
      immunodiagnostic methods have good application and development prospect because
      of high sensitivity and specificity, simple and convenient, and time saving. In
      this article, we review the main progress and application of immunodiagnostic
      methods for Giardia infection.

PMID- 29469543
TI  - [Advances in automatic detection technology for images of thin blood film of
      malaria parasite].
AB  - This paper reviews the computer vision and image analysis studies aiming at
      automated diagnosis or screening of malaria in microscope images of thin blood
      film smears. On the basis of introducing the background and significance of
      automatic detection technology, the existing detection technologies are
      summarized and divided into several steps, including image acquisition, pre
      processing, morphological analysis, segmentation, count, and pattern
      classification components. Then, the principles and implementation methods of
      each step are given in detail. In addition, the promotion and application in
      automatic detection technology of thick blood film smears are put forwarded as
      questions worthy of study, and a perspective of the future work for realization
      of automated microscopy diagnosis of malaria is provided.

PMID- 29469544
TI  - [Strongyloides stercoralis infection with hypothyroidism: one case report].
AB  - This paper reports the diagnosis and treatment of one rare case of thyroid
      dysfunction caused by Strongyloides stercoralis infection.

PMID- 29469545
TI  - [A case of dermatitis caused by Tyrophagus putrescentiae].
AB  - Here we report a case of dermatitis caused by Tyrophagus putrescentiae, and have
      reviewed the related literature, then summarize the clinical characteristics and
      treatments of dermatitis in order to improve the understanding of the disease.

PMID- 29469546
TI  - Reverse triggering with breath stacking in ARDS patients: the "optimum" can be
      the enemy of the "good".

PMID- 29469547
TI  - Workload and severity of illness of patients on intensive care units with
      available intermediate care units: a multicenter cohort study.
AB  - BACKGROUND: Intermediate Care Units (IMCU) are established in many hospitals to
      better match the requirements of patient care with respect to their personnel,
      equipment and other resources. This should relieve Intensive Care Unit (ICU)
      capacities for more severely ill patients and reduce readmissions to ICU. This
      study was conducted to investigate the effects of IMCU use on ICU populations.
      METHODS: This is a retrospective analysis of the German National Registry of
      Intensive Care from the years 2000 to 2010. RESULTS: We included 39 ICUs with
      high and 11 ICUs with low IMCU use. Patients in ICUs with high IMCU use were
      younger (mean age [high vs. low]: 60.5 vs. 64.5 years, P<0.001), while the
      severity of illness was higher (percentage of ventilated patients during ICU stay
      [high vs. low ICMU use]: 67.2% vs. 40.2%, P<0.001; patients ventilated >24 hours:
      22% vs. 18%, P<0.001; mean therapeutic intervention scoring system-28 (TISS-28)
      score: 25.7 vs. 23.3, P<0.001). Readmission rates to ICU did not differ between
      ICU groups ([high vs. low]: 4.5% vs. 4.4%, P=0.25). ICUs with high IMCU use
      discharged 90.3% of all patients who were discharged to the IMCU or general ward
      between the regular workday hours of 06:00 and 14:59, while ICUs with low IMCU
      use discharged 83.8% of all patients discharged to the general ward in the same
      time period. CONCLUSIONS: The use of IMCUs influences resource utilization of
      ICUs. Severity of illness and workload was higher in ICUs with high IMCU and more
      scheduled discharges occurred during the main working hours while readmission
      rates were similar.

PMID- 29469548
TI  - Pectoral nerve block and persistent pain following breast cancer surgery: an
      observational cohort study.

PMID- 29469549
TI  - Evolution of supraglottic airway devices: the Darwinian perspective.

PMID- 29469550
TI  - Chest wall blocks and minimally invasive image-guide procedures: the meeting
      point between radiology and anesthesiology that could improve safety and patient
      outcomes in NORA.

PMID- 29469551
TI  - Don't Try This at Home: the FDA's Restrictive Regulation of Home Testing Devices.
AB  - Over the past forty years, the Food and Drug Administration (FDA) has
      successfully restricted consumers' access to home-testing applications based on
      the notion that it should protect individuals from their own reactions to test
      results. In the 1970s, the FDA briefly denied women access to home pregnancy
      tests that were identical to those used in laboratories. In the late 1980s and
      early 1990s, it relied on concerns about consumer responses to HIV status results
      to justify a categorical ban on applications for HIV home-testing technology.
      More recently, it placed burdensome restrictions on direct-to-consumer (DTC)
      genetic testing companies, such as 23andMe, based on fears that consumerswould
      make irrational medical decisions after receiving genetic variant results.
      Although the FDA has the statutory authority to ensure the "safety and
      effectiveness" of medical devices, it has expansively interpreted the term
      "safety" to encompass considerations of how consumers might use test results
      provided by purely informative devices. This Noteargues that courts should not
      give the FDA deference on its broad interpretation of safety" in restricting home
      testing devices. It documents the evolution of the expertise-based rationale for
      judicial deference, noting that courts typically provide scientific agencies,
      including the FDA, "super deference" because of the complicated nature of their
      work. Ultimately, courts should not defer to the FDA's interpretation of "safety"
      because it did not use its scientific expertisewhen it considered how consumers
      might react to HIV home-testing and DTC genetic testing results. Further, the FDA
      should not have the authority to make decisions based on its view of "safety"
      because it should not have the power to make value judgments for consumers about
      whether they should seek their personal medical information.

PMID- 29469552
TI  - Preventive Therapies for Chronic Migraine.

PMID- 29469553
TI  - Preventive Therapies for Chronic Migraine.

PMID- 29469554
TI  - A Violent Birth: Reframing Coerced Procedures During Childbirth as Obstetric
      Violence.
AB  - In the United States, women are routinely forced to undergo cesarean sections,
      episiotomies, and the use of forceps, despite their desire to attempt natural
      vaginal delivery. Yet, the current American legal system does little to provide
      redress for women coerced to undergo certain medical procedures during
      childbirth. Courts and physicians alike are prepared to override a woman's choice
      of childbirth procedure if they believe this choice poses risks to the fetus, and
      both give little value to the woman's right to bodily autonomy. This Note
      proposes a solution for addressing the problem of coerced medical procedures
      during childbirth by importing a framework created in Venezuela and Argentina
      that characterizes this issue as "obstetric violence." First, this Note contains
      an overview of the shortcomings of the existing American legal framework to
      address the problem. Second, it explains the advantages of the obstetric violence
      framework and argues that its adoption in the United States would address many of
      the failures of the existing system. And third, this Note introduces a few
      legislative and litigation strategies that can be used to implement this
      framework in the United States and briefly addresses some of the challenges these
      strategies may pose.

PMID- 29469555
TI  - Tofacitinib for Psoriatic Arthritis.

PMID- 29469556
TI  - Prosthesis Type for Aortic- and Mitral-Valve Replacement.

PMID- 29469557
TI  - Prosthesis Type for Aortic- and Mitral-Valve Replacement.

PMID- 29469558
TI  - Prosthesis Type for Aortic- and Mitral-Valve Replacement.

PMID- 29469559
TI  - Prosthesis Type for Aortic- and Mitral-Valve Replacement.

PMID- 29469560
TI  - Rechargeable Aluminum-Ion Battery Based on MoS2 Microsphere Cathode.
AB  - In recent years, a rechargeable aluminum-ion battery based on ionic liquid
      electrolyte is being extensively explored due to three-electron electrochemical
      reactions, rich resources, and safety. Herein, a rechargeable Al-ion battery
      composed of MoS2 microsphere cathode, aluminum anode, and ionic liquid
      electrolyte has been fabricated for the first time. It can be found that Al3+
      intercalates into the MoS2 during the electrochemical reaction, whereas the
      storage mechanisms of the electrode material interface and internal are quite
      different. This result is confirmed by ex situ X-ray photoelectron spectroscopy
      and X-ray diffraction etching techniques. Meanwhile, this aluminum-ion battery
      also shows excellent electrochemical performance, such as a discharge specific
      capacity of 253.6 mA h g-1 at a current density of 20 mA g-1 and a discharge
      capacity of 66.7 mA h g-1 at a current density of 40 mA g-1 after 100 cycles.
      This will lay a solid foundation for the commercialization of aluminum-ion
      batteries.

PMID- 29469561
TI  - Free-Standing Porous Carbon Nanofiber/Carbon Nanotube Film as Sulfur Immobilizer
      with High Areal Capacity for Lithium-Sulfur Battery.
AB  - Low sulfur utilization and poor cycle life of the sulfur cathode with high sulfur
      loadings remain a great challenge for lithium-sulfur (Li-S) battery. Herein, the
      free-standing carbon film consisting of porous carbon nanofibers (PCNFs) and
      carbon nanotubes (CNTs) is successfully fabricated by the electrospinning
      technology. The PCNF/CNT film with three-dimensional and interconnected structure
      is promising for the uniformity of the high-loading sulfur, good penetration of
      the electrolyte, and reliable accommodation of volumetric expansion of the sulfur
      cathode. In addition, the abundant N/O-doped elements in PCNF/CNT film are
      helpful to chemically trap soluble polysulfides in the charge-discharge
      processes. Consequently, the obtained monolayer S/PCNF/CNT film as the cathode
      shows high specific capacity, excellent cycle stability, and rate stability with
      the sulfur loading of 3.9 mg cm-2. Moreover, the high areal capacity of 13.5 mA h
      cm-2 is obtained for the cathode by stacking three S/PCNF/CNT layers with the
      high sulfur loading of 12 mg cm-2. The stacking-layered cathode with high sulfur
      loading provides excellent cycle stability, which is beneficial to fabricate high
      energy-density Li-S battery in future.

PMID- 29469562
TI  - Surface Topography Hinders Bacterial Surface Motility.
AB  - We demonstrate that the surface motility of the bacterium, Pseudomonas
      aeruginosa, is hindered by a crystalline hemispherical topography with wavelength
      in the range of 2-8 MUm. The motility was determined by the analysis of time
      lapse microscopy images of cells in a flowing growth medium maintained at 37 
      degrees C. The net displacement of bacteria over 5 min is much lower on surfaces
      containing 2-8 MUm hemispheres than on flat topography, but displacement on the 1
      MUm hemispheres is not lower. That is, there is a threshold between 1 and 2 MUm
      for response to the topography. Cells on the 4 MUm hemispheres were more likely
      to travel parallel to the local crystal axis than in other directions. Cells on
      the 8 MUm topography were less likely to travel across the crowns of the
      hemispheres and were also more likely to make 30 degrees -50 degrees  turns than
      on flat surfaces. These results show that surface topography can act as a
      significant barrier to surface motility and may therefore hinder surface
      exploration by bacteria. Because surface exploration can be a part of the process
      whereby bacteria form colonies and seek nutrients, these results help to
      elucidate the mechanism by which surface topography hinders biofilm formation.

PMID- 29469563
TI  - Real-Time Tunable Colors from Microfluidic Reconfigurable All-Dielectric
      Metasurfaces.
AB  - Structural colors arising from all-dielectric nanostructures are very promising
      for high-resolution color nanoprinting and high-density optical storage. However,
      once the all-dielectric nanostructures are fabricated, their optical performances
      are usually static or change slowly, significantly limiting the practical
      applications in advanced displays. Herein, we experimentally demonstrate the real
      time tunable colors with microfluidic reconfigurable all-dielectric metasurfaces.
      The metasurface is composed of an array of TiO2 nanoblocks, which are embedded in
      a polymeric microfluidic channel. By injecting solutions with a different
      refractive index into the channel, the narrow band reflection peak and the
      corresponding distinct colors of a TiO2 metasurface can be precisely controlled.
      The transition time is as small as 16 ms, which is orders of magnitude faster
      than the current techniques. By varying the lattice size of TiO2 metasurfaces,
      the real-time tunable colors are able to span the entire visible spectrum.
      Meanwhile, the injection and ejection of solvent have also shown the capability
      of the erasion and the restoration of information encoded in TiO2 metasurfaces.
      The combination of all-dielectric nanostructures with microfluidic channels shall
      boost their applications in functional color display, banknote security,
      anticounterfeiting, and point-of-care devices.

PMID- 29469564
TI  - MXene as a Charge Storage Host.
AB  - The development of efficient electrochemical energy storage (EES) devices is an
      important sustainability issue to realize green electrical grids. Charge storage
      mechanisms in present EES devices, such as ion (de)intercalation in lithium-ion
      batteries and electric double layer formation in capacitors, provide insufficient
      efficiency and performance for grid use. Intercalation pseudocapacitance (or
      redox capacitance) has emerged as an alternative chemistry for advanced EES
      devices. Intercalation pseudocapacitance occurs through bulk redox reactions with
      ultrafast ion diffusion. In particular, the metal carbide/nitride nanosheets
      termed MXene discovered in 2011 are a promising class of intercalation
      pseudocapacitor electrode materials because of their compositional versatility
      for materials exploration (e.g., Ti2CT x, Ti3C2T x, V2CT x, and Nb2CT x, where T
      is a surface termination group such as F, Cl, O, or OH), high electrical
      conductivity for high current charge, and a layered structure of stacked
      nanosheets for ultrafast ion intercalation. Various MXene electrodes have been
      reported to exhibit complementary battery performance, such as large specific
      capacity at high charge/discharge rates. However, general design strategies of
      MXenes for EES applications have not been established because of the limited
      understanding of the electrochemical mechanisms of MXenes. This Account describes
      current knowledge of the fundamental electrochemical properties of MXenes and
      attempts to clarify where intercalation capacitance ends and intercalation
      pseudocapacitance begins. MXene electrodes in aqueous electrolytes exhibit
      intercalation of hydrated cations. The hydrated cations form an electric double
      layer in the interlayer space to give a conventional capacitance within the
      narrow potential window of aqueous electrolytes. When nonaqueous electrolytes are
      used, although solvated cations are intercalated into the interlayer space during
      the initial stage of charging, the confined solvation shell should gradually
      collapse because of the large inner potential difference in the interlayer space.
      Upon further charging, desolvated ions solely intercalate, and the atomic
      orbitals of the desolvated cations overlap with the orbitals of MXene to form a
      donor band. The formation of the donor band induces the reduction of MXene,
      giving rise to an intercalation pseudocapacitance through charge transfer from
      the ions to MXene sheets. Differences in the electrochemical reaction mechanisms
      lead to variation of the electrochemical responses of MXenes (e.g., cyclic
      voltammetry curves, specific capacitance), highlighting the importance of
      establishing a comprehensive grasp of the electrochemical reactions of MXenes at
      an atomic level. Because of their better charge storage kinetics compared with
      those of typical materials used in present EES devices, aqueous/nonaqueous
      asymmetric capacitors using titanium carbide MXene electrodes are capable of
      efficient operation at high charge/discharge rates. Therefore, the further
      development of novel MXene electrodes for advanced EES applications is warranted.

PMID- 29469565
TI  - Reduced Graphene Oxide-Incorporated SnSb@CNF Composites as Anodes for High
      Performance Sodium-Ion Batteries.
AB  - Sodium-ion batteries (SIBs) are promising alternatives to lithium-ion batteries
      because of the low cost and natural abundance of sodium resources. Nevertheless,
      low energy density and poor cycling stability of current SIBs unfavorably hinder
      their practical implementation for the smart power grid and stationary storage
      applications. Antimony tin (SnSb) is one of the most promising anode materials
      for next-generation SIBs attributing to its high capacity, high abundance, and
      low toxicity. However, the practical application of SnSb anodes in SIBs is
      currently restricted because of their large volume changes during cycling, which
      result in serious pulverization and loss of electrical contact between the active
      material and the carbon conductor. Herein, we apply reduced graphene oxide (rGO)
      incorporated SnSb@carbon nanofiber (SnSb@rGO@CNF) composite anodes in SIBs that
      can sustain their structural stability during prolonged charge-discharge cycles.
      Electrochemical performance results shed light on that the combination of rGO,
      CNF, and SnSb alloy led to a high-capacity anode (capacity of 490 mAh g-1  at the
      10th cycle) with a high capacity retention of 87.2% and a large Coulombic
      efficiency of 97.9% at the 200th cycle. This work demonstrates that the
      SnSb@rGO@CNF composite is a potential and attractive anode material for next
      generation, high-energy SIBs.

PMID- 29469566
TI  - Commercially Available Activated Carbon Fiber Felt Enables Efficient Solar Steam
      Generation.
AB  - Sun-driven steam generation is now possible and has the potential to help meet
      future energy needs. Current technologies often use solar condensers to increase
      solar irradiance. More recently, a technology for solar steam generation that
      uses heated surface water and low optical concentration is reported. In this
      work, a commercially available activated carbon fiber felt is used to generate
      steam efficiently under one sun illumination. The evaporation rate and solar
      conversion efficiency reach 1.22 kg m-2 h-1 and 79.4%, respectively. The local
      temperature of the evaporator with a floating activated carbon fiber felt reaches
      48  degrees C. Apart from the high absorptivity (about 94%) of the material, the
      evaporation performance is enhanced thanks to the well-developed pores for
      improved water supply and steam escape and the low thermal conductivity, which
      enables reduced bulk water temperature increase. This study helps to find a
      promising material for solar steam generation using a water evaporator that can
      be produced economically (~6 $/m2) with long-term stability.

PMID- 29469567
TI  - Compact-Nanobox Engineering of Transition Metal Oxides with Enhanced Initial
      Coulombic Efficiency for Lithium-Ion Battery Anodes.
AB  - A novel strategy is proposed to construct a compact-nanobox (CNB) structure
      composed of irregular nanograins (average diameter ~ 10 nm), aiming to confine
      the electrode-electrolyte contact area and enhance initial Coulombic efficiency
      (ICE) of transition metal oxide (TMO) anodes. To demonstrate the validity of this
      attempt, CoO-CNB is taken as an example which is synthesized via a carbothermic
      reduction method. Benefiting from the compact configuration, electrolyte can only
      contact the outer surface of the nanobox, keeping the inner CoO nanograins
      untouched. Therefore, the solid electrolyte interphase (SEI) formation is
      reduced. Furthermore, the internal cavity leaves enough room for volume variation
      upon lithiation and delithiation, resulting in superior mechanical stability of
      the CNB structure and less generation of fresh SEI. Consequently, the SEI remains
      stable and spatially confined without degradation, and hence, the CoO-CNB
      electrode delivers an enhanced ICE of 82.2%, which is among the highest values
      reported for TMO-based anodes in lithium-ion batteries. In addition, the CoO-CNB
      electrode also demonstrates excellent cyclability with a reversible capacity of
      811.6 mA h g-1 (90.4% capacity retention after 100 cycles). These findings open
      up a new way to design high-ICE electrodes and boost the practical application of
      TMO anodes.

PMID- 29469568
TI  - Venturing beyond Donor-Controlled Glycosylation: New Perspectives toward Anomeric
      Selectivity.
AB  - Glycans are complex compounds consisting of sugars linked glycosidically,
      existing either as pure polysaccharides or as part of glycoconjugates. They are
      prevalent in nature and possess important functions in regulating biological
      pathways. However, their diversity coupled with physiochemical similarities makes
      it challenging to isolate them in large quantities for biochemical studies, hence
      hampering progress in glycobiology and glycomedicine. Glycochemistry presents an
      alternative strategy to obtain pure glycan compounds through artificial synthetic
      methods. Efforts in glycochemistry have been centered on glycosylation, the key
      reaction in glycochemistry, especially with regards to anomeric stereoselectivity
      in polysaccharides and glycoconjugates. In particular, the stereoelectronic and
      steric properties of glycosyl donors are commonly used to direct the
      stereoselectivity in glycosylation reactions. Classic glycosylation strategies
      typically involve saturated glycosyl donors, proceeding either directly using
      hydrogen bonds and conformational constraints or indirectly by installing
      moieties covalently through neighboring group participation and intramolecular
      aglycon delivery. Over the past years, new glycosylation strategies, tapping on
      the foundations of transition metal catalysis, have emerged. To leverage the
      power of coordination chemistry, unsaturated glycosyl donors were introduced. Not
      only are the number of protection/deprotection steps reduced, the resultant
      unsaturated glycoside provides opportunities for downstream functionalizations,
      allowing quick access to a variety of sugars, including rare sugars. Alongside
      the glycosyl donor, an equally important but neglected aspect for targeting
      stereoselective glycosylation is the glycosyl acceptor. In the case of dual
      directing donors, glycosyl acceptors have proved themselves capable of becoming
      the dominating factor for stereocontrol. Interestingly, rational manipulation or
      selection of glycosyl acceptors with particular nucleophilicity and p Ka values
      can lead to different stereoselectivities, thereby proving the tunability of such
      acceptors to favor the formation of one anomer over the other stereoselectively.
      By further venturing beyond substrate controlled stereoselectivity, we are
      presented with the opportunity to effect stereoselective glycosylation through
      glycosylating reagents. Of the key reagents, stereoselective catalyst stands out
      as a greener and efficient alternative to direct stereoselective control with
      stoichiometric substrates. Recently, investigations into this approach of
      stereocontrol presented an intriguing range of stereoselectivities, achieved by
      merely varying the nature of catalysts used. Another crucial effort in
      glycochemistry is enhancing the efficiencies of glycosylations, by reducing the
      number of preparative steps before or during glycosylation. Through using
      transient masking groups or one-pot synthetic strategies, these streamlined
      approaches provide enormous convenience and practicability for oligosaccharide
      syntheses. This Account presents mainly our advancements beyond the conventional
      donor-controlled strategies over the past decade, with emphasis placed on
      mechanistic explanations of anomeric selectivities, thereby providing
      perspectives to inspire further progress toward a generalized unified strategy
      for preparing every type of glycan.

PMID- 29469569
TI  - Role of Metal Electronegativity in the Dehydrogenation Thermodynamics and
      Kinetics of Composite Metal Borohydride-LiNH2 Hydrogen Storage Materials.
AB  - The composites of M(BH4) n-LiNH2 (1/2 n molar ratio, n = 1 or 2, M = Ca, Mg, Li)
      were synthesized by liquid ball milling. Samples were characterized by X-ray
      diffraction, thermogravimetry-differential thermal analysis-mass spectroscopy (TG
      DTA-MS), and kinetic models (Achar differential/Coats-Redfern integral method).
      The higher-electronegativity metal M in M(BH4) n-4LiNH2 (M = Ca, Mg) samples not
      only enables [BH4]- group to release easily, so as to facilitate the interaction
      of [BH4]- and [NH2]- groups, but also restrains the NH3 release and slightly
      decreases the onset dehydrogenation temperature concluded by TG-MS. Moreover, in
      stage 1 (200-350  degrees C), the kinetics performances of M(BH4) n-4LiNH2 (M =
      Ca, Mg) samples are distinctly improved, that is, the activation energies of them
      are reduced by ca. 30% compared to those of sample LiBH4-2LiNH2. The outstanding
      contribution of the replacement of M(BH4) n with high-electronegativity metal ion
      is to both improve the kinetics performance by changing the kinetics mechanism
      and decrease the temperature range of the initial dehydrogenation region.

PMID- 29469570
TI  - Ribemansides A and B, TRPC6 Inhibitors from Ribes manshuricum That Suppress TGF
      beta1-Induced Fibrogenesis in HK-2 Cells.
AB  - Two new acylated beta-hydroxynitrile glycosides, ribemansides A (1) and B (2),
      were isolated from the aerial parts of Ribes manshuricum. Their structures were
      elucidated by comprehensive spectroscopic analysis. Ribemansides A and B
      inhibited transforming growth factor beta1 (TGF-beta1)-induced expression of
      alpha-smooth muscle actin, fibronectin release, and changes in cell morphology in
      the human proximal tubular epithelial cell line (human kidney-2, HK-2). Further
      biological evaluation demonstrated that both 1 and 2 inhibit the activity of
      canonical transient receptor potential cation channel 6 (TRPC6), with IC50 values
      of 24.5 and 25.6 MUM, respectively. The antifibrogenic effect of these compounds
      appears to be mediated through TRPC6 inhibition, since the TRPC6 inhibitor,
      SAR7334, also suppressed TGF-beta1-induced fibrogenesis in HK-2 cells.

PMID- 29469571
TI  - Single-Step In Situ Acetylcholinesterase-Mediated Alginate Hydrogelation for
      Enzyme Encapsulation in CE.
AB  - A novel capillary electrophoresis-integrated immobilized enzyme reactor (CE
      integrated IMER) is developed using single-step in situ acetylcholinesterase
      (AChE)-mediated alginate hydrogelation and enzyme encapsulation. Alginate
      hydrogelation with "egg-box" structure is triggered inside a capillary with
      releasing of Ca2+ by changing the pH of the sol solution, which is accomplished
      in situ by AChE-catalyzed hydrolysis reaction of acetylthiocholine to produce
      acetic acid. AChE and any other enzyme initially contained in the sol solution
      [e.g., xanthine oxidase (XO)] are efficiently encapsulated as the hydrogel
      network grows, forming CE-integrated IMERs without any additional manipulation
      process. The proposed method facilitates the analysis of different kinds of
      enzymes using the same IMER depending on the substrate injected for CE analysis.
      Approximately 68% of the original enzyme in the sol mixture can be encapsulated,
      indicating high loading capacity for the CE-integrated IMERs. The IMERs exhibit
      excellent intraday and interday stability and batch-to-batch reproducibility, and
      these characteristics imply the reliability of the proposed IMERs for accurate
      online enzyme assays. Enzymatic activities and inhibition of immobilized AChE and
      XO are analyzed, and the results are compared with those using free enzymes. The
      feasibility of the proposed method for potential application in real sample
      analysis is demonstrated by the successful application of the IMERs in detecting
      organophosphorus pesticides in apple juice samples using AChE-catalyzed
      reactions. The proposed method is a simple, efficient, and universal approach for
      online CE assays with immobilized enzymes, which can be widely applied in
      bioanalysis.

PMID- 29469572
TI  - Multiple Pathways in the Self-Assembly Process of a Pd4L8 Coordination
      Tetrahedron.
AB  - The self-assembly of a Pd418 coordination tetrahedron (Tet) from a ditopic
      ligand, 1, and palladium(II) ions, [PdPy*4]2+ (Py* = 3-chloropyridine), was
      investigated by a 1H NMR-based quantitative approach (quantitative analysis of
      self-assembly process, QASAP), which allows one to monitor the average
      composition of the intermediates not observed by NMR spectroscopy. The self
      assembly of Tet takes place mainly through three pathways and about half of the
      Tet structures were produced through the reaction of a kinetically produced Pd3L6
      double-walled triangle (DWT) and 200-nm-sized large intermediates (IntL). In two
      of the three pathways, the leaving ligand (Py*), which is not a component of Tet,
      catalytically assisted the self-assembly. Such a multiplicity of the self
      assembly process of Tet suggests that molecular self-assembly takes place on an
      energy landscape like a protein-folding funnel.

PMID- 29469574
TI  - Control of Excitation Energy Transfer in Condensed Phase Molecular Systems by
      Floquet Engineering.
AB  - Excitation energy transfer (EET) is one of the most important processes in both
      natural and artificial chemical systems including, for example, photosynthetic
      complexes and organic solar cells. The EET rate, however, is strongly suppressed
      when there is a large difference in the excitation energy between the donor and
      acceptor molecules. Here, we demonstrate both analytically and numerically that
      the EET rate can be greatly enhanced by periodically modulating the excitation
      energy difference. The enhancement of EET by using this Floquet engineering, in
      which the system's Hamiltonian is made periodically time-dependent, turns out to
      be efficient even in the presence of strong fluctuations and dissipations induced
      by the coupling with a huge number of dynamic degrees of freedom in the
      surrounding molecular environments. As an effect of the environment on the
      Floquet engineering of EET, the optimal driving frequency is found to depend on
      the relative magnitudes of the system and environment's characteristic time
      scales with an observed frequency shift when moving from the limit of slow
      environmental fluctuations (inhomogeneous broadening limit) to that of fast
      fluctuations (homogeneous broadening limit).

PMID- 29469573
TI  - Nonconjugated Acyloxy Group Deactivates the Intramolecular Charge-Transfer State
      in the Carotenoid Fucoxanthin.
AB  - We used ultrafast transient absorption spectroscopy to study excited-state
      dynamics of the keto-carotenoid fucoxanthin (Fx) and its two derivatives: 19'
      butanoyloxyfucoxanthin (bFx) and 19'-hexanoyloxyfucoxanthin (hFx). These
      derivatives occur in some light-harvesting systems of photosynthetic
      microorganisms, and their presence is typically related to stress conditions.
      Even though the hexanoyl (butanoyl) moiety is not a part of the conjugated system
      of hFx (bFx), their absorption spectra in polar solvents exhibit more pronounced
      vibrational bands of the S2 state than for Fx. The effect of the nonconjugated
      acyloxy moiety is further observed in transient absorption spectra, which for Fx
      exhibit characteristic features of an intramolecular charge transfer (ICT) state
      in all polar solvents. For bFx and hFx, however, much weaker ICT features are
      detected in methanol, and the spectral markers of the ICT state disappear
      completely in polar, but aprotic acetonitrile. The presence of the acyloxy moiety
      also alters the lifetimes of the S1/ICT state. For Fx, the lifetimes are 60, 30,
      and 20 ps in n-hexane, acetonitrile, and methanol, whereas for bFx and hFx, these
      lifetimes yield 60, 60, and 40 ps, respectively. Testing the S1/ICT state
      lifetimes of hFx in other solvents revealed that some ICT features can be induced
      only in polar, protic solvents (methanol, ethanol, and ethylene glycol). Thus,
      bFx and hFx represent a rather rare example of a system in which a nonconjugated
      functional group significantly alters excited-state dynamics. By comparison with
      other carotenoids, we show that a keto group at the acyloxy tail, even though it
      is not in conjugation, affects the electron distribution along the conjugated
      backbone, resulting in the observed decrease of the ICT character of the S1/ICT
      state of bFx and hFx.

PMID- 29469575
TI  - Herbicidins from Streptomyces sp. CB01388 Showing Anti- Cryptosporidium Activity.
AB  - A high-content imaging assay was used to screen the fraction collection of the
      Natural Product Library at The Scripps Research Institute for inhibitors of
      Cryptosporidium parvum. A chemical investigation of one strain, Streptomyces sp.
      CB01388, resulted in the isolation of six herbicidins (1-6), one of which is new
      (herbicidin L, 1). Five of the six herbicidins (1-3, 5, 6) showed moderate
      inhibitory activity against C. parvum, with 1 and 6 comparable to the FDA
      approved drug nitazoxanide, and 2-6 showed no toxicity to the host HCT-8 cells
      and human HEK293T and HepG2 cells. These findings highlight the herbicidin
      scaffold for anti- Cryptosporidium drug development.

PMID- 29469576
TI  - Structure and Relaxation in Solutions of Monoclonal Antibodies.
AB  - Reversible self-association of therapeutic antibodies is a key factor in high
      protein solution viscosities. In the present work, a coarse-grained computational
      model accounting for electrostatic, dispersion, and long-ranged hydrodynamic
      interactions of two model monoclonal antibodies is applied to understand the
      nature of self-association, predicting the solution microstructure and resulting
      transport properties of the solution. For the proteins investigated, the
      structure factor across a range of solution conditions shows quantitative
      agreement with neutron-scattering experiments. We observe a homogeneous,
      dynamical association of the antibodies with no evidence of phase separation.
      Calculations of self-diffusivity and viscosity from coarse-grained dynamic
      simulations show the appropriate trends with concentration but, respectively,
      over- and under-predict the experimentally measured values. By adding constraints
      to the self-associated clusters that rigidify them under flow, prediction of the
      transport properties is significantly improved with respect to experimental
      measurements. We hypothesize that these rigidity constraints are associated with
      missing degrees of freedom in the coarse-grained model resulting from patchy and
      heterogeneous interactions among coarse-grained domains. These results
      demonstrate how structural anisotropy and anisotropy of interactions generated by
      features at the 2-5 nm length scale in antibodies are sufficient to recover the
      dynamics and rheological properties of these important macromolecular solutions.

PMID- 29469577
TI  - Rhodium-Catalyzed Asymmetric Arylative Ring-Opening Reactions of Heterobicyclic
      Alkenes with Anilines.
AB  - Asymmetric arylative ring-opening reactions of heterobicyclic alkenes with
      anilines have been reported for the first time. A wide range of heterobicyclic
      alkenes, including azabenzonorbornadienes and oxabenzonorbornadienes, were well
      tolerated in the reaction with various anilines, and they generally delivered the
      corresponding chiral aryltetralin derivatives in good to excellent
      enantioselectivities. The reaction is speculated to proceed through the Friedel
      Crafts reaction pathway.

PMID- 29469578
TI  - A Stereoselective Reductive Hosomi-Sakurai Reaction.
AB  - A novel reductive variant of the classical Hosomi-Sakurai reaction is reported.
      This transformation hinges on a redox-neutral, stereoselective internal reduction
      event under mild conditions. This operationally simple reaction relies on readily
      available starting materials and leads to useful products in
      diastereoselectivities of up to 7:1. The versatility of this new method is
      demonstrated through the stereoselective one-step synthesis of an AChE inhibitor.

PMID- 29469579
TI  - Big data in psychology: A framework for research advancement.
AB  - The potential for big data to provide value for psychology is significant.
      However, the pursuit of big data remains an uncertain and risky undertaking for
      the average psychological researcher. In this article, we address some of this
      uncertainty by discussing the potential impact of big data on the type of data
      available for psychological research, addressing the benefits and most
      significant challenges that emerge from these data, and organizing a variety of
      research opportunities for psychology. Our article yields two central insights.
      First, we highlight that big data research efforts are more readily accessible
      than many researchers realize, particularly with the emergence of open-source
      research tools, digital platforms, and instrumentation. Second, we argue that
      opportunities for big data research are diverse and differ both in their fit for
      varying research goals, as well as in the challenges they bring about.
      Ultimately, our outlook for researchers in psychology using and benefiting from
      big data is cautiously optimistic. Although not all big data efforts are suited
      for all researchers or all areas within psychology, big data research prospects
      are diverse, expanding, and promising for psychology and related disciplines.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29469580
TI  - The psychometric properties of the Personality Assessment Inventory-Adolescent's
      Borderline Features Scale across two high-risk samples.
AB  - The present study sought to assess the performance of the Borderline Features
      (BOR) Scale of the adolescent version of the Personality Assessment Inventory
      (Morey, 2007b) in 2 high-risk samples: inpatient and justice-involved
      adolescents. This study is the first to evaluate the BOR scale in high-risk
      adolescent samples, outside the initial standardization studies. Across both
      samples (NClinical = 327, NForensic = 151), results indicated good internal
      consistency. Confirmatory factor analysis indicated poor fit of the 4-factor
      structure proposed by the measure's authors. Convergent validity and receiver
      operating characteristics analyses, conducted in the clinical sample, indicated
      that the adolescent version of the Personality Assessment Inventory BOR scale had
      good diagnostic accuracy for predicting a borderline personality disorder
      diagnosis (via structured interview). Findings suggest that the BOR scale has
      adequate internal consistency, convergent validity, and clinical utility,
      although areas for future measure evaluation (including factor structure) remain.
      Still, the BOR scale may partially address the current hesitation to assess
      borderline personality disorder features in high-risk youth because it is
      embedded within a broadband psychopathology measure. (PsycINFO Database Record

PMID- 29469581
TI  - A comprehensive examination of the psychometric properties of the Hare
      Psychopathy Checklist-Revised in a Canadian multisite sample of indigenous and
      non-indigenous offenders.
AB  - The present study examined the psychometric properties of Hare Psychopathy
      Checklist-Revised (PCL-R; Hare, 2003) scores in a multisite sample of 1,163
      federally incarcerated Canadian indigenous and non-indigenous offenders from the
      Prairie Region of the Correctional Service of Canada. The research occurred
      against the backdrop of the Ewert v. Canada (2015) matter, in which the PCL-R was
      originally impugned in Federal Court for use with indigenous persons (later
      overturned in Canada v. Ewert, 2016). Indigenous men scored higher than non
      indigenous men on most components of the PCL-R and had higher rates of
      recidivism, irrespective of follow-up. Discrimination analyses, however,
      supported the predictive efficacy of PCL-R total, factor, and facet scores for
      violent and general recidivism across both ancestral groups, with most group
      differences in area under the curve (AUC) magnitudes being small and
      nonsignificant. Calibration analyses demonstrated that higher PCL-R scores were
      associated with higher rates of general and violent recidivism for both ancestral
      groups, although higher recidivism rates were observed and estimated for
      indigenous men at specific PCL-R score thresholds. Confirmatory factor analyses
      supported the 4-factor model of psychopathy and hence, structural invariance, of
      PCL-R scores across ancestral groups. Structural equation modeling affirmed the
      predictive efficacy of the 4-factor model for recidivism. We discuss these
      findings in terms of clinical applications of the PCL-R and the psychopathy
      construct in general, with male offenders of indigenous ancestry. (PsycINFO
      Database Record

PMID- 29469582
TI  - Contrasting hemispheric asymmetries for emotional processing from event-related
      potentials and behavioral responses.
AB  - OBJECTIVE: Four main theories concerning hemispheric asymmetries for emotional
      processing have been proposed: the right hemisphere hypothesis (RHH; the right
      hemisphere is specialized in processing all emotions), the valence hypothesis
      (VH; the left and the right hemispheres are superior in positive and negative
      emotion processing, respectively), the modified VH (the right-hemispheric
      superiority at posterior sites is followed by a valence-specific activity at
      frontal sites), and the motivational model (the left and the right hemispheres
      are superior in approaching-related and avoidance-related emotions,
      respectively). METHOD: In a divided visual field paradigm, we presented happy and
      angry faces to 16 healthy participants, either unilaterally or bilaterally, in
      order to test the aforementioned theories. RESULTS: Behavioral results provided
      support for the VH and correlational analysis revealed that handedness influences
      the rightward bias for positive emotions. The amplitude of P1, N170, and P2 event
      related potential components at parietal sites (selected by means of topographic
      maps) was larger in the right than in the left hemisphere, independently of the
      emotional expression of the stimuli, supporting the RHH. At frontal sites, no
      asymmetry was found in bilateral conditions, whereas in unilateral conditions, a
      mixed pattern of hemispheric asymmetries emerged. CONCLUSIONS: We conclude that
      there is no correspondence between behavioral and electrophysiological results
      concerning asymmetries for emotion processing, and that the VH and the RHH are
      not mutually exclusive. (PsycINFO Database Record

PMID- 29469583
TI  - Cognitive flexibility and dual processing in pigeons: Temporal and contextual
      control of midsession reversal.
AB  - Evidence is reported showing that pigeons flexibly use temporal and contextual
      cues to maximize reward obtained in a midsession reversal task. Pigeons were
      trained to choose between red and green sidekeys for 60 trials in a session, with
      choice of one color correct on Trials 1-30 and choice of the other color correct
      on Trials 31-60 (midsession reversal). Pigeons showed anticipatory errors before
      reversal and perseverative errors after reversal, and manipulations of the length
      of the intertrial interval and the point of reversal suggested that pigeons used
      an internal timer to track the point of reversal. When houselight context cues
      that signaled the correct choice were presented throughout trials in Experiment
      1, choice behavior rapidly came under context control, leading pigeons to rarely
      make errors and to show no effect of intertrial interval or point of reversal. In
      Experiments 2 and 3, switches between context and no-context cues occurred among
      trials. These manipulations revealed that pigeons can readily switch between
      context control and temporal control of behavior. The internal timer continued to
      run throughout context trials and could readily be accessed to control choice
      behavior when a context cue was removed. (PsycINFO Database Record

PMID- 29469584
TI  - Paid sick leave status in relation to government sponsored welfare utilization.
AB  - Nearly a third of all U.S. workers, primarily lower-paid employees, do not have
      paid sick leave benefits, prompting some lawmakers to consider mandating paid
      sick leave for all U.S. employees so workers can access timely health care
      without lost wages. A representative sample of 19,537 workers in current paid
      employment was examined, searching for the association between access to paid
      sick leave benefits and receipt of six different welfare and welfare-related
      services. After controlling for relevant demographic, work, income, and
      medical/health care variables, results of the logistic models indicate that,
      among working adults age 18-64, those without paid sick leave are 1.41 times more
      likely to receive income from a state or county welfare program, 1.36 times more
      likely to receive other welfare assistance (transportation and child care
      supports), 1.33 times more likely to received sponsored rental assistance, and
      1.34 times more likely to receive Supplemental Nutrition Assistance Program
      benefits (referred to as food stamps commonly and in this article). Mandating
      paid sick leave benefits may impact usage of social welfare assistance since
      families with paid sick leave do not have to lose wages when work is missed
      because of health and caregiver responsibilities. (PsycINFO Database Record

PMID- 29469585
TI  - Proactive aggression in early school-aged children with externalizing behavior
      problems: A longitudinal study on the influence of empathy in response to
      distress.
AB  - The course of proactive aggressive behavior may be affected by empathy in
      response to sadness and distress of others. The aim of the current study is to
      examine empathy in response to sadness and distress and its relation to proactive
      and reactive aggression in a clinical sample of children with externalizing
      behavior problems. At baseline (T1) and 12 months later (T2), parents and
      teachers of 104 six- and seven-year-old children completed the Instrument for
      Reactive and Proactive Aggression. At T1, parents and teachers also reported
      empathy in response to sadness and distress on the Griffith Empathy Measure.
      Findings show that low levels of parent-reported empathy at baseline were
      specifically associated with high parent-reported proactive aggression but not
      with reactive aggression. Similarly, low teacher-reported empathy was
      specifically related to high teacher-reported proactive aggression. Furthermore,
      high parent-reported but not teacher-reported empathy at baseline was associated
      with low proactive aggression at 12 months after controlling for proactive
      aggression at baseline. The conclusions support the notion that in the study of
      the course of aggression in clinical groups, the distinction between proactive
      and reactive aggression as well as the study of empathy in response to distress
      is relevant for a better understanding and might be taken into account in the
      development of future interventions. (PsycINFO Database Record

PMID- 29469586
TI  - Fixation reinstatement supports visuospatial memory in older adults.
AB  - Research using eye movement monitoring suggests that recapitulating the pattern
      of eye movements made during stimulus encoding at subsequent retrieval supports
      memory by reinstating the spatial layout of the encoded stimulus. In the present
      study, the authors investigated whether recapitulation of encoding fixations
      during a poststudy, stimulus-free delay period-an effect that has been previously
      linked to memory maintenance in younger adults-can support mnemonic performance
      in older adults. Older adults showed greater delay-period fixation reinstatement
      than younger adults, and this reinstatement supported age-equivalent performance
      on a subsequent visuospatial-memory-based change detection task, whereas in
      younger adults, the performance-enhancing effects of fixation reinstatement
      increased with task difficulty. Taken together, these results suggest that
      fixation reinstatement might reflect a compensatory response to increased
      cognitive load. The present findings provide novel evidence of compensatory
      fixation reinstatement in older adults and demonstrate the utility of eye
      movement monitoring for aging and memory research. (PsycINFO Database Record

PMID- 29469587
TI  - Simulational fluency reduces feelings of psychological distance.
AB  - Why do some events feel "like yesterday" whereas others feel "ages away"? Past
      research has identified cues that influence people's estimates of distance in
      units such as how many miles or days away events are from the self. However, what
      makes events feel psychologically close or distant? We examine the hypothesis
      that increased simulational fluency, the ease with which people mentally imagine
      events, makes events feel psychologically close. Simulational fluency was
      associated with feelings that multiple past and future holidays were
      psychologically close (Studies 1a and 1b). Writing short, easy-to-generate
      descriptions of Christmas made it feel psychologically closer and more fluently
      simulated compared with writing longer, difficult-to-generate descriptions (Study
      2). This pattern was not anticipated by readers of the same content who did not
      directly experience the fluency of writing descriptions. Writing descriptions of
      Halloween made it feel fluently simulated and psychologically close, even as
      concrete "how" descriptions reduced construal level compared with abstract "why"
      descriptions (Study 3). Listening to a fluent audio description of a past Super
      Bowl, compared with a disfluent audio description, caused the game to feel
      psychologically closer in both space and time (Study 4). Reading a description of
      the Super Bowl in easy-to-read font, compared with difficult-to-read font, made
      the game feel more fluently simulated and psychologically closer (Study 5). These
      findings have implications for theories of psychological distance and its role in
      everyday life. (PsycINFO Database Record

PMID- 29469588
TI  - Robust, replicable, and theoretically-grounded: A response to Brown and Coyne's
      (2017) commentary on the relationship between emodiversity and health.
AB  - In 2014 in the Journal of Experimental Psychology: General, we reported 2 studies
      demonstrating that the diversity of emotions that people experience-as measured
      by the Shannon-Wiener entropy index-was an independent predictor of mental and
      physical health, over and above the effect of mean levels of emotion. Brown and
      Coyne (2017) questioned both our use of Shannon's entropy and our analytic
      approach. We thank Brown and Coyne for their interest in our research; however,
      both their theoretical and empirical critiques do not undermine the central
      theoretical tenets and empirical findings of our research. We present an in-depth
      examination that reveals that our findings are statistically robust, replicable,
      and reflect a theoretically grounded phenomenon with real-world implications.
      (PsycINFO Database Record

PMID- 29469589
TI  - Preparation of Vitamin E-Containing High-Density Lipoprotein and Its Protective
      Efficacy on Macrophages.
AB  - Atherosclerosis is a major cause for cardiovascular diseases. High-density
      lipoprotein (HDL) may reduce atherosclerosis through several different
      mechanisms. HDL is composed of lipids, cholesterol, cholesteryl esters,
      triglycerides, and phospholipids, mainly phosphatidylcholine plus specialized
      proteins called apolipoproteins (apos). In this study, we prepared vitamin E
      containing HDL (VE-HDL) that contains egg phosphatidylcholine, cholesterol,
      vitamin E, and two kinds of recombinant human apolipoproteins (rhapo)-rhapoA-I
      and rhapoE in vitro by the facilitation of cholate. After that, we studied the
      effects of VE-HDL on foam cell formation, cellular cholesterol efflux, oxidative
      low-density lipoprotein (oxLDL)-stimulated oxidative stress, and apoptosis of
      macrophages to evaluate the protective efficacy of VE-HDL on macrophages. As the
      results showed, we prepared a new type of reconstituent HDL with apolipoproteins
      and vitamin E for the first time. VE-HDL has protective efficacy on macrophages.
      It has the prospect of becoming a therapeutic agent on atherosclerosis in the
      future.

PMID- 29469590
TI  - Association of physical functioning of persons with dementia with caregiver
      burden and depression in dementia caregivers: an integrative data analysis.
AB  - OBJECTIVES: To determine whether caregiver relationship and race modify
      associations between physical functioning of persons with dementia (PWD) and
      their caregiver's burden and general depressive symptoms. METHOD: We pooled data
      from four behavioral intervention trials (N = 1,211). Using latent growth
      modeling, we evaluated associations of PWD physical functioning with the level
      and rate of change in caregiver burden and caregivers' general depressive
      symptoms and stratified these associations by caregiver relationship and race.
      RESULTS: PWD were, on average, 81 years old (68% female) with mean follow-up of
      0.5 years. More baseline PWD physical impairment was associated with less
      worsening in caregiver burden over time (beta = -0.23, 95% CI: -0.29, -0.14), but
      this relationship was not modified by caregiver characteristics. More impaired
      baseline PWD physical functioning was not associated with changes in depressive
      symptoms (beta = -0.08, 95% CI: -0.17, 0.00), but was associated with less
      worsening in depressive symptoms among spousal (beta = -0.08, 95% CI: -0.17,
      0.00) and non-white (beta = -0.08, 95% CI: -0.17, 0.00) caregivers. CONCLUSIONS:
      Dementia caregivers may experience reduced caregiver-related burden because of
      adjustment to PWD functional status, while spousal and non-white caregivers may
      experience less depressive symptoms resultant of adjustment to functional status.

PMID- 29469591
TI  - Associations of health insurance coverage, mental health problems, and drug use
      with mental health service use in US adults: an analysis of 2013 National Survey
      on Drug Use and Health.
AB  - OBJECTIVE: To estimate the prevalence of mental health service use among US
      adults, examine the associations of mental health service use with health
      insurance coverage, mental health problems and drug use, and detect health
      disparities. METHODS: This was a cross-sectional study with 5,434 adults
      receiving mental health service out of 37,424 adult respondents from the 2013
      National Survey on Drug Use and Health. Weighted univariate and multiple logistic
      regression analyses were used to estimate the associations of potential factors
      with mental health service use. RESULTS: The overall prevalence of mental health
      services use was 14.7%. Our results showed that being female, aging, having a
      major depressive episode, serious psychological distress, and illicit drug or
      alcohol abuse/dependence were positively associated with mental health service
      use; whereas being African American, Asian or Hispanic ethnicity, married, and
      having any form of insurance were negatively associated with mental health
      service use . Stratified analysis by insurance types showed that Medicaid/CHIP,
      CHAMPUS, and other insurance were positively associated with mental health
      service use. CONCLUSIONS: Health insurance coverage, mental health problems, and
      drug abuse or dependence were associated with mental health service use in US
      adults. Furthermore, adults with different insurances had disparities in access
      of mental health service.

PMID- 29469592
TI  - Ixazomib in the management of relapsed multiple myeloma.
AB  - The development of proteasome inhibitors contributed to the dramatic life
      expectancy improvement observed in myeloma patients over the past decades.
      Ixazomib is a boron-containing selective and reversible proteasome inhibitor that
      demonstrated antimyeloma activity with excellent safety profile. Ixazomib is the
      first orally available proteasome inhibitor approved in combination with
      lenalidomide and dexamethasone for the treatment of myeloma patients who received
      at least one prior therapy. The present review addresses the current knowledge
      regarding the clinical use of ixazomib in relapsed myeloma patients.

PMID- 29469593
TI  - l-Carnosine as Adjunctive Therapy in Children and Adolescents with Attention
      Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled
      Clinical Trial.
AB  - OBJECTIVES: This study aimed to investigate the efficacy and tolerability of l
      carnosine as an add-on to methylphenidate in management of children with
      attention-deficit/hyperactivity disorder (ADHD). METHODS: This was an 8-week,
      randomized, double-blind placebo-controlled study. Fifty-six drug-free children
      and adolescents aged 6-17 years old with a diagnosis of ADHD entered the study.
      The patients were randomly assigned to l-carnosine (800 mg/d in two divided
      doses) or placebo plus methylphenidate (0.5-1.5 mg/kg/d) for 8 weeks. Children
      were assessed using the Teacher and Parent ADHD Rating Scale-IV (ADHD-RS-IV) at
      baseline and at weeks 4 and 8 postbaseline. RESULTS: Fifty patients completed the
      study, and all had two postbaseline measurements. Using the general linear model
      repeated measures, significant effect was observed for time * treatment
      interaction on total and inattention subscales of the Parent ADHD-RS (Greenhouse
      Geisser corrected: F = 3.783, df = 1.444, p = 0.041 and F = 4.032, df = 1.600, p
      = 0.030). Improvements in the Teacher ADHD-RS were not significantly different
      between the two groups in total (Greenhouse-Geisser corrected: F = 0.200, df =
      1.218, p = 0.705), as well as inattention and hyperactivity subscale scores (p =
      0.956 and 0.281, respectively). The frequency of side effects was not
      significantly different between the two treatment arms. CONCLUSIONS: l-carnosine,
      as a supplementary medication, might be beneficial in treatment of children with
      ADHD. However, further investigations and different doses of l-carnosine are
      required to replicate these findings in children with ADHD.

PMID- 29469595
TI  - Combined treatment for skin laxity of the aging face with monopolar
      radiofrequency and intense focused ultrasound in Korean subjects.
AB  - BACKGROUND: Although various minimal invasive approaches are available for aging
      skin laxity, they alone may not lead to notably satisfactory results. OBJECTIVE:
      To evaluate the effectiveness and safety of combination regimen with monopolar
      radiofrequency (MRF) and intense-focused ultrasound (IFUS) in facial lifting and
      tightening. METHODS: Twenty-two Korean participants with aging face received a
      sequential single session of MRF and IFUS treatment. Objective and subjective
      assessments for improvement were performed at the 20-week post-treatment. Safety
      profiles were also recorded, and skin biopsies were taken at baseline and follow
      up visit. RESULTS: Based on the objective assessment for the overall facial skin
      tightening and laxity, 19 patients (90%) demonstrated "moderate" or better
      improvements (more than 25%) compared with baseline. Specifically, improvements
      of skin laxity and sagging, and droopy jaw line were more noticeable compared
      with that of superficial skin texture (P < 0.05). Subjective satisfactions were
      generally consistent with objective findings, and no serious adverse effect was
      observed. Histologic evaluation showed increased dermal collagen fibers
      throughout the dermis after treatments (P < 0.05). CONCLUSION: Combination
      treatment of MRF and IFUS has cumulative benefits for skin lifting and tightening
      with satisfactory safety profiles in Asian subjects.

PMID- 29469594
TI  - Positional effects revealed in Illumina methylation array and the impact on
      analysis.
AB  - AIM: We aimed to prove the existence of positional effects in the Illumina
      methylation beadchip data and to find an optimal correction method. MATERIALS &
      METHODS: Three HumanMethylation450, three HumanMethylation27 datasets and two
      EPIC datasets were analyzed. ComBat, linear regression, functional normalization
      and single-sample Noob were used for minimizing positional effects. The corrected
      results were evaluated by four methods. RESULTS: We detected 52,988 CpG loci
      significantly associated with sample positions, 112 remained after ComBat
      correction in the primary dataset. The pre- and postcorrection comparisons
      indicate the positional effects could alter the measured methylation values and
      downstream analysis results. CONCLUSION: Positional effects exist in the Illumina
      methylation array and may bias the analyses. Using ComBat to correct positional
      effects is recommended.

PMID- 29469596
TI  - Genome-scale metabolic models as platforms for identification of novel genes as
      antimicrobial drug targets.
AB  - The growing number of multidrug-resistant pathogenic bacteria is becoming a world
      leading challenge for the scientific community and for public health. However,
      advances in high-throughput technologies and whole-genome sequencing of bacterial
      pathogens make the construction of bacterial genome-scale metabolic models (GEMs)
      increasingly realistic. The use of GEMs as an alternative platforms will expedite
      identification of novel unconditionally essential genes and enzymes of target
      organisms with existing and forthcoming GEMs. This approach will follow the
      existing protocol for construction of high-quality GEMs, which could ultimately
      reduce the time, cost and labor-intensive processes involved in identification of
      novel antimicrobial drug targets in drug discovery pipelines. We discuss the
      current impact of existing GEMs of selected multidrug-resistant pathogenic
      bacteria for identification of novel antimicrobial drug targets and the
      challenges of closing the gap between genome-scale metabolic modeling and
      conventional experimental trial-and-error approaches in drug discovery pipelines.

PMID- 29469597
TI  - Treatment of multiple eccrine hidrocystoma with oral isotretinoin following
      erbium-yttrium aluminum garnet laser.
AB  - Eccrine hidrocystomes (EH) are benign cystic tumors of dermal eccrine ducts.
      There is still no gold standard treatment option for EH because of the large
      number of lesions, the risk of cicatrization and the different treatment options
      offered. We offer combined oral isotretinoin and following erbium-yttrium
      aluminum garnet laser treatment as an alternative treatment option in difficult
      patients with EH.

PMID- 29469598
TI  - Supporting ethics educators in Canadian occupational therapy and physical therapy
      programs: A national interprofessional knowledge exchange project.
AB  - Ethics education is the cornerstone of professional practice, fostering knowledge
      and respect for core ethical values among healthcare professionals. Ethics is
      also a subject well-suited for interprofessional education and collaboration.
      However, there are few initiatives to gather experiences and share resources
      among ethics educators in rehabilitation. We thus undertook a knowledge exchange
      project to: 1) share knowledge about ethics training across Canadian occupational
      and physical therapy programs, and 2) build a community of educators dedicated to
      improving ethics education. The objectives of this paper are to describe this
      interprofessional knowledge exchange project involving ethics educators (with a
      diversity of professional and disciplinary backgrounds) from Canadian
      occupational and physical therapy programs as well as analyze its outcomes based
      on participants' experiences/perceptions. Two knowledge exchange strategies were
      employed: an interactive one-day workshop and a wiki platform. An immediate post
      workshop questionnaire evaluated the degree to which participants' expectations
      were met. Structured telephone interviews 9-10 months after the workshop
      collected participants' perceptions on whether (and if so, how) the project
      influenced their teaching or led to further interprofessional collaborations.
      Open-ended questions from the post-workshop questionnaires and individual
      interviews were analyzed using qualitative methods. Of 40 ethics educators
      contacted, 23 participated in the workshop and 17 in the follow-up interview.
      Only 6 participants logged into the wiki from its launch to the end of data
      collection. Five themes emerged from the qualitative analysis: 1) belonging and
      networking; 2) sharing and collaborating; 3) changing (or not) ways of teaching
      ethics; 4) sustaining the network; and 5) envisioning the future of ethics
      education. The project attained many of its goals, despite encountering some
      challenges. While the wiki platform proved to be of limited benefit in advancing
      the project goals, the interactive format and collaborative nature of the one-day
      workshop were described as rewarding and effective in bringing together
      occupational therapy and physical therapy educators to meet, network, and share
      knowledge.

PMID- 29469599
TI  - Effects of gait training with non-paretic knee immobilization on patients with
      hemiplegia: Three single-case studies.
AB  - Patients' with a hemiplegic gait and difficulties with activities of daily living
      may improve through intensive training of their paretic lower limbs. This study
      examined the possibility of improving their gait by immobilizing the non-paretic
      knee joint in extension and promoting weight shift toward the paretic side.
      Single-case ABABA studies were conducted, involving three patients with
      hemiplegia. The patients walked with their non-paretic knee joints immobilized in
      extension using a dial-lock knee orthosis during the intervention (B1 and B2)
      periods. Measurement items included (1) temporal and distance factors and (2)
      hip, knee, and ankle joint angles during gait. In all subjects, the stance phase
      was significantly prolonged on the paretic side during all intervention periods
      following the first baseline (A1) period. In Subject 1, hip extension in the
      stance phase improved during all intervention periods following the A1 period,
      and, in Subjects 2 and 3, the knee hyperextension in the stance phase, which was
      observed during the A1 period, was resolved during the second (A2) and third (A3)
      baseline periods. Gait training with non-paretic knee immobilization may promote
      weight shift toward the paretic side to overcome a swing limitation on the
      immobilized side, consequently providing an opportunity for training in weight
      bearing for the paretic limb and an improved, more symmetrical gait pattern.

PMID- 29469600
TI  - Development and Standardization of Moringa oleifera Leaves as a Natural Dietary
      Supplement.
AB  - Moringa oleifera leaves were selected as a model due to their hundreds of health
      benefits. On the other hand, the powder of these leaves has exhibited poor
      flowability, low tensile strength, bitter taste, poor dissolution rate, and lack
      of information regarding dosage. These are the common hurdles and limitations in
      the adaptation of herbal-based medications. Therefore, a comprehensive study was
      planned to introduce herbal-based medicines into mainstream medicines by
      standardization according to the U.S. Food and Drug Administration (FDA) and
      international pharmaceutical standards. A Simplex Lattice Design (SLD) of Design
      Expert 8.0 software was used to formulate different concentrations of
      superdisintegrant, binder/diluent, and sweeteners. An Instron Universal Testing
      machine coupled with a 13 mm stainless cylindrical die was used to manufacture
      tablets by means of direct compression method at 20 kN applied force. Therefore,
      selection of excipients was made on the basis of their tensile strength,
      flowability, and taste-masking properties. Optimum formulation was tested on
      rabbits for toxicity and growth rate. All formulated tablets were evaluated on
      standard parameters for orally disintegrating tablets described by the Food and
      Drug Authority (U.S.). The optimum formulation fulfills all standard parameters
      such as hardness, disintegration time, friability, and dissolution rate. The
      present formulation showed no toxicity when tested on rabbits. The present study
      provides a fundamental understanding of the tableting characteristics of natural
      medicines. The present study provides information that will help to overcome the
      challenges.

PMID- 29469601
TI  - The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a
      Randomized Study in Humans.
AB  - PURPOSE: Netarsudil, an inhibitor of Rho kinase and a norepinephrine transporter,
      has been shown to lower elevated intraocular pressure (IOP) in controlled studies
      of patients with open-angle glaucoma and ocular hypertension, and in healthy
      volunteers. The mechanism of this ocular hypotensive effect in humans is unknown.
      METHODS: The objective of this study was to evaluate the effect of netarsudil
      0.02% on aqueous humor dynamics (AHD) parameters. In this double-masked, vehicle
      controlled, paired-eye comparison study, 11 healthy volunteers received topical
      netarsudil ophthalmic solution 0.02% or its vehicle once daily for 7 days
      (morning dosing). The primary endpoints were the change in AHD parameters,
      compared between active and vehicle-treated eyes. RESULTS: In netarsudil-treated
      eyes, diurnal outflow facility increased from 0.27 +/- 0.10 MUL/min/mmHg to 0.33
      +/- 0.11 MUL/min/mmHg (+22%; P = 0.02) after 7 days of treatment. In placebo
      treated eyes, diurnal outflow facility did not significantly change (P = 0.94).
      The difference between netarsudil and placebo eyes in diurnal change of outflow
      facility was 0.08 MUL/min/mmHg (P < 0.001). Diurnal episcleral venous pressure
      (EVP) in netarsudil-treated eyes decreased from 7.9 +/- 1.2 mmHg to 7.2 +/- 1.8 (
      10%; P = 0.01). Diurnal EVP was not significantly different between netarsudil-
      and placebo-treated eyes. There was a trend toward decreasing aqueous humor flow
      rate (-15%; P = 0.08). No treatment changes were seen in uveoscleral outflow
      rate. CONCLUSIONS: Once-daily dosing of netarsudil ophthalmic solution 0.02%
      lowered IOP through increasing trabecular outflow facility and reducing EVP. This
      suggests a combination of mechanisms that affect both the proximal and distal
      outflow pathways.

PMID- 29469602
TI  - Can 5 minutes of repetitive prone press-ups and sustained prone press-ups
      following a period of spinal loading reverse spinal shrinkage?
AB  - OBJECTIVE: The objective of this study is to investigate if sustained and
      repetitive prone press-ups could reverse decreased spinal height following spinal
      loading and if there was a correlation between the degree of end range of motion
      spinal extension and spinal height gains. DESIGN: Pretest-posttest crossover
      design is used in this study. SETTING: Study was carried out in research
      laboratory. SUBJECTS: Forty-one healthy men and women were included in this
      study. INTERVENTION: Participants were seated in the stadiometer for 5 min with a
      4.5-kg weight placed on each shoulder; the load was removed for 5 min and spinal
      height was measured using a stadiometer before and after 5 min of repetitive or
      sustained prone press-ups. MAIN MEASURES: Two-by-two repeated-measures ANOVA to
      identify significant interactions and main effects is used in this study.
      Significance of alpha = 0.05. A Pearson correlation coefficient was used to
      assess the correlation between spinal height changes and spinal extension ROM.
      RESULTS: Participants 24.1 +/- 2.03 years grew using both repetitive (4.85 +/-
      3.01 mm) and sustained press ups (4.46 +/- 2.57 mm). There was no significant
      interaction between the repetitive versus sustained press-ups and the time before
      and after each prone press-ups strategy and no main effect for strategy
      (sustained vs. repetitive press-ups). There was a significant main effect for
      time (before vs. after press-ups) (F(1,30) = 140.771; p < 0.0001; partial eta2 =
      0.82). No correlation was found between the degree of end ROM spinal extension
      and spinal height changes following press-ups strategies. CONCLUSION: Following
      periods of spinal loading, both repetitive and sustained press-ups increased
      spinal height. Such strategies could be used to help recover spinal height and
      limit the effects of decreased spinal height as a result of activities of daily
      living.

PMID- 29469603
TI  - Extended local similarity analysis (eLSA) reveals unique associations between
      bacterial community structure and odor emission during pig carcasses
      decomposition.
AB  - Soil burial and composting methods have been widely used for the disposal of pig
      carcasses. The relationship between bacterial community structure and odor
      emission was examined using extended local similarity analysis (eLSA) during the
      degradation of pig carcasses in soil and compost. In soil, Hyphomicrobium,
      Niastella, Rhodanobacter, Polaromonas, Dokdonella and Mesorhizobium were
      associated with the emission of sulfur-containing odors such as hydrogen sulfide,
      methyl mercaptan and dimethyl disulfide. Sphingomonas, Rhodanobacter,
      Mesorhizobium, Dokdonella, Leucobacter and Truepera were associated with the
      emission of nitrogen-containing odors including ammonia and trimetylamine. In
      compost, however, Carnobacteriaceae, Lachnospiaceae and Clostridiales were highly
      correlated with the emission of sulfur-containing odors, while Rumincoccaceae was
      associated with the emission of nitrogen-containing odors. The emission of
      organic acids was closely related to Massilia, Sphaerobacter and
      Bradyrhizobiaceae in soil, but to Actinobacteria, Sporacetigenium,
      Micromonosporaceae and Solirubrobacteriales in compost. This study suggests that
      network analysis using eLSA is a useful strategy for exploring the mechanisms of
      odor emission during biodegradation of pig carcasses.

PMID- 29469605
TI  - Mundt et al. paper: "Does occupational exposure to formaldehyde cause
      hematotoxicity and leukemia-specific chromosome changes in cultured myeloid
      progenitor cells?"

PMID- 29469604
TI  - Dissolved organic matter and aluminum oxide nanoparticles synergistically cause
      cellular responses in freshwater microalgae.
AB  - This study investigated the impact of dissolved organic matters (DOM) on the
      ecological toxicity of aluminum oxide nanoparticles (Al2O3NPs) at a relatively
      low exposure concentration (1 mg L-1). The unicellular green alga Scenedesmus
      obliquus was exposed to Al2O3NP suspensions in the presence of DOM (fulvic acid)
      at various concentrations (1, 10, and 40 mg L-1). The results show that the
      presence of DOM elevated the growth inhibition toxicity of Al2O3NPs towards S.
      obliquus in a dose-dependent manner. Moreover, the combination of DOM at 40 mg L
      1 and Al2O3NPs resulted in a synergistic effect. The relative contribution of Al
      ions released from Al2O3NPs to toxicity was lower than 5%, indicating that the
      presence of the particles instead of the dissolved ions in the suspensions was
      the major toxicity sources, regardless of the presence of DOM. Furthermore, DOM
      at 10 and 40 mg L-1 and Al2O3NPs synergistically induced the upregulation of
      intercellular reactive oxygen species levels and superoxide dismutase activities.
      Analysis of the plasma malondialdehyde concentrations and the observation of
      superficial structures of S. obliquus indicated that the mixtures of DOM and
      Al2O3NPs showed no significant effect on membrane lipid peroxidation damage. In
      addition, the presence of both DOM and Al2O3NPs contributed to an enhancement in
      both the mitochondrial membrane potential and the cell membrane permeability
      (CMP) in S. obliquus. In particular, Al2O3NPs in the presence of 10 and 40 mg L-1
      DOM caused a greater increase in CMP compared to Al2O3NPs and DOM alone
      treatments. In conclusion, these findings suggest that DOM at high concentrations
      and Al2O3NPs synergistically interrupted cell membrane functions and triggered
      subsequent growth inhibition toxicity.

PMID- 29469606
TI  - Detection of a rare CYP3A4 variant in a transplant patient characterized by a
      tacrolimus poor metabolizer phenotype.
AB  - A validated CYP3A genotype classification system allows clustering patients into
      poor, intermediate and extensive metabolizer phenotypes. However, substantial
      overlap exists between the clusters. A rare CYP3A4 allele, named CYP3A4*20
      (rs67666821), has been specifically described in the Spanish population. The
      authors investigated the relevance of CYP3A4*20 testing to see if the above
      mentioned metabolic CYP3A classification system can be improved. In a cohort of
      204 kidney transplant recipients, one male patient carrying a CYP3A4*20 allele
      was detected. This patient was receiving very low doses of tacrolimus to maintain
      therapeutic levels from day 7 onward when compared with the majority of the
      patients. These data suggest that this patient should be regarded as a CYP3A-poor
      metabolizer.

PMID- 29469607
TI  - Packed in-tube solid phase microextraction with graphene oxide supported on
      aminopropyl silica: Determination of target triazines in water samples.
AB  - On-line in-tube solid phase microextraction (in-tube SPME) coupled to high
      performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS) was
      successfully applied to the determination of selected triazines in water samples.
      The method based on the employment of a packed column containing graphene oxide
      (GO) supported on aminopropyl silica (Si) showed that the extraction phase has a
      high potential for triazines extraction aiming to its physical-chemical
      properties including ultrahigh specific surface area, good mechanical and thermal
      stability and high fracture strength. Injection volume and loading time were both
      investigated and optimized. The method validation using Si-GO to extract and
      concentrate the analytes showed satisfactory results, good sensitivity, good
      linearity (0.2-4.0 ug L-1) and low detection limits (1.1-2.9 ng L-1). The high
      extraction efficiency was determined with enrichment factors ranging from 1.2-2.9
      for the lowest level, 1.3-4.9 intermediate level and 1.2-3.0 highest level (n =
      3). Although the analytes were not detected in the real samples evaluated, the
      method has demonstrated to be efficient through its application in the analysis
      of spiked triazines in ground and mineral water samples.

PMID- 29469608
TI  - BCL11A and MDR1 expressions have prognostic impact in patients with acute myeloid
      leukemia treated with chemotherapy.
AB  - : Acute myeloid leukemia (AML) is a heterogeneous malignant disease. Many
      different genetic factors can affect a patient's clinical outcome. AIM: The aim
      of this study was to assess the expression of BCL11A and MDR1 in AML patients,
      and its relation to clinical outcome. MATERIALS & METHODS: We grouped the 142
      patients by the levels of BCL11A and MDR1 and identified three different
      subgroups: high BCL11A and high MDR1 (n = 47), low BCL11A and low MDR1 (n = 47)
      and high BCL11A alone or high MDR1 alone (n = 48). RESULTS: The results showed
      that AML patients with high BCL11A and MDR1 expression had the lowest complete
      remission and highest relapse rate. The median overall survival of the high
      BCL11A and high MDR1 group was the shortest among the three groups. With regards
      to overall survival, there were also significant differences among the groups (p
      < 0.001). CONCLUSION: High BCL11A and MDR1 expression was associated with a poor
      response to chemotherapy, and identified a subset of AML patients with a very
      poor prognosis.

PMID- 29469609
TI  - Diversity of antibiotic resistance genes and encoding ribosomal protection
      proteins gene in livestock waste polluted environment.
AB  - The rapid development and increase of antibiotic resistance are global phenomena
      resulting from the extensive use of antibiotics in human clinics and animal
      feeding operations. Antibiotics can promote the occurrence of antibiotic
      resistance genes (ARGs), which can be transferred horizontally to humans and
      animals through water and the food chain. In this study, the presence and
      abundance of ARGs in livestock waste was monitored by quantitative PCR. A diverse
      set of bacteria and tetracycline resistance genes encoding ribosomal protection
      proteins (RPPs) from three livestock farms and a river were analyzed through
      denaturing gradient gel electrophoresis (DGGE). The abundance of sul(I) was 103
      to 105 orders of magnitude higher than that of sul(II). Among 11 tet-ARGs, the
      most abundant was tet(O). The results regarding bacterial diversity indicated
      that the presence of antibiotics might have an evident impact on bacterial
      diversity at every site, particularly at the investigated swine producer. The
      effect of livestock waste on the bacterial diversity of soil was stronger than
      that of water. Furthermore, a sequencing analysis showed that tet(M) exhibited
      two genotypes, while the other RPPs-encoding genes exhibited at least three
      genotypes. This study showed that various ARGs and RPPs-encoding genes are
      particularly widespread among livestock.

PMID- 29469610
TI  - Comparative analysis between biofilm formation and gene expression in
      Staphylococcus epidermidis isolates.
AB  - AIM: To understand the relationship between ica, aap and bhp gene expression and
      the implications in biofilm formation in selected clinical and commensal
      Staphylococcus epidermidis isolates. MATERIAL & METHODS: Isolates were analyzed
      regarding their biofilm-forming capacity, biochemical matrix composition, biofilm
      spatial organization and expression of biofilm-related genes. RESULTS: On
      polysaccharide intercellular adhesin-dependent biofilms, aap and bhp
      contributions for the biofilm growth were negligible, despite very high levels of
      expression. In contrast, smaller increases in icaA expression contributed
      significantly to biofilm growth. Interestingly, no biological differences were
      observed between clinical and commensal strains. CONCLUSION: These results
      reinforce the concept that S. epidermidis is an 'accidental pathogen,' and that
      the ica operon is the main mechanism of biofilm formation in clinical and
      commensal isolates.

PMID- 29469611
TI  - Scoring analysis of the men's 2014, 2015 and 2016 world championship tour of
      surfing: the importance of aerial manoeuvres in competitive surfing.
AB  - The aim of this study was to investigate the impact of aerial manoeuvres on
      scoring in professional surfing. 23,631 waves were analysed for the number and
      types of aerial manoeuvres performed from the 2014, 2015 and 2016 Men's World
      Championship Tour. Additionally, the awarded score, timing and order of the
      aerial was also analysed. Descriptive statistics and Two Way ANOVA's were
      performed with Sidak Multiple Comparisons Post Hoc analysis. Results were a
      significantly higher score being awarded (P <= 0.0001) when including an aerial
      in competition across all three seasons. In 2015 surfers were awarded a
      significantly larger score when performing an air reverse, compared to 2014 (P =
      0.0002) and 2016 (P = 0.0057). Surfers were also awarded a higher score for the
      full rotation aerial in 2015 compared to 2014 (P = 0.0177). In 2015 surfers
      performing forehand aerials were awarded a greater score than in 2016 (P =
      0.0113). The timing of the aerial and score awarded was significantly greater in
      2015 as opposed to 2014 when the aerial was their final manoeuvre (P < 0.0001)
      and when surfers timed the aerial performance early within the heat (P = 0.0027).
      If a surfer incorporates an aerial manoeuvre during competition, generally
      speaking, they will be awarded a significantly higher score.

PMID- 29469612
TI  - The atypical chemokine receptor ACKR2 drives pulmonary fibrosis by tuning influx
      of CCR2+ and CCR5+ IFNgamma-producing gammadeltaT cells in mice.
AB  - Chemokines coordinate lung inflammation and fibrosis by acting on chemokine
      receptors expressed on leukocytes and other cell types. Atypical chemokine
      receptors (ACKRs) bind, internalize, and degrade chemokines, tuning homeostasis
      and immune responses. ACKR2 recognizes and decreases the levels of inflammatory
      CC chemokines. The role of ACKR2 in fibrogenesis is unknown. The purpose of the
      study was to investigate the role of ACKR2 in the context of pulmonary fibrosis.
      The effects of ACKR2 expression and deficiency during inflammation and fibrosis
      were analyzed using a bleomycin-model of fibrosis, ACKR2-deficient mice, bone
      marrow chimeras, and antibody-mediated leukocyte depletion. ACKR2 was upregulated
      acutely in response to bleomycin and normalized over time. ACKR2-/- mice showed
      reduced lethality and lung fibrosis. Bone marrow chimeras showed that lethality
      and fibrosis depended on ACKR2 expression in pulmonary resident
      (nonhematopoietic) cells but not on leukocytes. ACKR2-/- mice exhibited decreased
      expression of tissue-remodeling genes, reduced leukocyte influx, pulmonary
      injury, and dysfunction. ACKR2-/- mice had early increased levels of CCL5, CCL12,
      CCL17, and IFNgamma and an increased number of CCR2+ and CCR5+ IFNgamma-producing
      gammadeltaT cells in the airways counterbalanced by low Th17-lymphocyte influx.
      There was reduced accumulation of IFNgamma-producing gammadeltaT cells in CCR2-/-
      and CCR5-/- mice. Moreover, depletion of gammadeltaT cells worsened the clinical
      symptoms induced by bleomycin and reversed the phenotype of ACKR2-/- mice exposed
      to bleomycin. ACKR2 controls the CC chemokine expression that drives the influx
      of CCR2+ and CCR5+ IFNgamma-producing gammadeltaT cells, tuning the Th17 response
      that mediated pulmonary fibrosis triggered by bleomycin instillation.

PMID- 29469613
TI  - Aging and anatomical variations in lung tissue stiffness.
AB  - Lung function is inherently mechanical in nature and depends on the capacity to
      conduct air and blood to and from the gas exchange regions. Variations in the
      elastic properties of the human lung across anatomical compartments and with
      aging are likely important determinants of lung function but remain relatively
      poorly characterized. Here we applied atomic force microscopy microindentation to
      characterize human lung tissue from subjects ranging in age from 11 to 60 yr old.
      We observed striking anatomical variations in elastic modulus, with the airways
      (200- to 350-um diameter) the stiffest and the parenchymal regions the most
      compliant. Vessels (diameter < 100 um) represented an intermediate mechanical
      environment and displayed diameter-dependent trends in elastic modulus. Binning
      our samples into younger (11-30 yr old) and older (41-60 yr old) groups, we
      observed significant age-related increases in stiffness in parenchymal and vessel
      compartments, with the most pronounced changes in the vessels. To investigate
      cellular mechanisms that might contribute to vascular stiffening with aging, we
      studied primary human pulmonary artery smooth muscle cells from subjects ranging
      in age from 11 to 60 yr old. While we observed no change in the mechanical
      properties of the cells themselves, we did observe trends toward increases in
      traction forces and extracellular matrix deposition with aging. These results
      demonstrate age-related changes in tissue mechanical properties that likely
      contribute to impaired lung function with aging and underscore the potential to
      identify mechanisms that contribute to mechanical tissue remodeling through the
      study of human cells and tissues from across the aging spectrum.

PMID- 29469615
TI  - Enhanced photodynamic therapy using light fractionation against Streptococcus
      mutans biofilm: type I and type II mechanism.
AB  - AIM: The objective of the study was to look the efficacy of fractionated light
      against Streptococcus mutans biofilm. MATERIALS & METHODS: Antibiofilm assays
      (crystal violet, congo red), electron microscopic, confocal and spectroscopic
      studies were performed to check the effect of fractionated light. RESULTS: 6-6.5
      log10 reduction of planktonic and 3.6-4.2 log10 reduction in biofilm were
      observed after irradiation with fractionated as compared with continuous light.
      Increased permeability to propidium iodide and leakage of cellular constituent
      validate the greater antibiofilm effect of fractionated light. Spectroscopic
      studies confirmed the relative contribution of type I and type II photochemistry.
      CONCLUSION: Phenothiazinium dyes have a potential against bacterial biofilm in
      combination with light fractionation and it offers new opportunities to explore
      its clinical implication.

PMID- 29469614
TI  - TGF-beta1-induced deposition of provisional extracellular matrix by tracheal
      basal cells promotes epithelial-to-mesenchymal transition in a c-Jun NH2-terminal
      kinase-1-dependent manner.
AB  - Epithelial cells have been suggested as potential drivers of lung fibrosis,
      although the epithelial-dependent pathways that promote fibrogenesis remain
      unknown. Extracellular matrix is increasingly recognized as an environment that
      can drive cellular responses in various pulmonary diseases. In this study, we
      demonstrate that transforming growth factor-beta1 (TGF-beta1)-stimulated mouse
      tracheal basal (MTB) cells produce provisional matrix proteins in vitro, which
      initiate mesenchymal changes in subsequently freshly plated MTB cells via Rho
      kinase- and c-Jun NH2-terminal kinase (JNK1)-dependent processes. Repopulation of
      decellularized lung scaffolds, derived from mice with bleomycin-induced fibrosis
      or from patients with idiopathic pulmonary fibrosis, with wild-type MTB cells
      resulted in a loss of epithelial gene expression and augmentation of mesenchymal
      gene expression compared with cells seeded into decellularized normal lungs. In
      contrast, Jnk1-/- basal cells seeded into fibrotic lung scaffolds retained a
      robust epithelial expression profile, failed to induce mesenchymal genes, and
      differentiated into club cell secretory protein-expressing cells. This new
      paradigm wherein TGF-beta1-induced extracellular matrix derived from MTB cells
      activates a JNK1-dependent mesenchymal program, which impedes subsequent normal
      epithelial cell homeostasis, provides a plausible scenario of chronic aberrant
      epithelial repair, thought to be critical in lung fibrogenesis. This study
      identifies JNK1 as a possible target for inhibition in settings wherein
      reepithelialization is desired.

PMID- 29469616
TI  - Prehospital Echocardiography During Resuscitation Impacts Treatment in a
      Physician-Staffed Helicopter Emergency Medical Service: an Observational Study.
AB  - BACKGROUND: Patients in cardiac arrest must receive algorithm-based management
      such as basic life support and advanced (cardiac) life support. International
      guidelines dictate diagnosing and treating any factor that may have caused the
      arrest or may be complicating the resuscitation. Ultrasound may be of potential
      value in this process and can be used in a prehospital setting. The objective is
      to evaluate the use of prehospital ultrasound during traumatic and non-traumatic
      CPR and determine its impact on prehospital treatment decisions in a Dutch
      helicopter emergency medical service (HEMS). METHODS: We conducted an
      observational study in cardiac arrest patients, of any cause, in whom the
      Nijmegen HEMS performed CPR with concurrent echocardiography. The participating
      physicians had to adhere to Advanced Life Support protocols as per standard
      operating procedure. Simultaneous with the interruptions of chest compressions to
      allow for heart rhythm analysis, ultrasound-trained HEMS physicians performed
      echocardiography according to study protocol. The HEMS nurse and physician
      recorded patient data and data on impacted (supported or altered) patient
      treatment decisions. RESULTS: From February 2014 through November 2016, we
      included 56 patients who underwent 102 ultrasound examinations. Sixty-two (61%)
      ultrasound examinations impacted 78 treatment decisions in 49 patients (88%). The
      impacted treatment was related to termination of CPR in 32 (57%), fluid
      management (14%), drugs selection and doses (14%), and choice of destination
      hospital (5%). Causes of cardiac arrest included trauma (48%), cardiac (21%),
      medical (14%), asphyxia (9%), and other (7%). CONCLUSION: Prehospital
      echocardiography has an impact on patient treatment and may be a useful tool to
      support decision-making during CPR in a Dutch HEMS.

PMID- 29469617
TI  - Are energy Drinks Scapegoats? Decomposing Teenagers' Caffeine intake from Energy
      Drinks and Soda Beverages.
AB  - BACKGROUND: Energy drinks have been repeatedly blamed for contributing to
      caffeine intake among teenagers. OBJECTIVES: This study aimed to estimate and
      compare the caffeine intake of US teenagers from soda drinks versus energy drinks
      and shots. METHODS: Data were taken from a 2015 nationally representative survey
      (Monitoring the Future) of 8th and 10th graders in the US (47.2% 8th grade; 51.1%
      female). Participants reported their numbers of consumed sodas, diet sodas,
      energy drinks, and energy shots per day. These were converted into mg
      caffeine/day and were contrasted with common guidelines for healthy caffeine
      intake, stratified by age group and sex. Error-bar charts, ANOVA and ROC curves
      were used for contrasting caffeine intake from soda drinks and energy drinks, as
      well as their contribution to exceeding recommended caffeine intake cutoffs.
      RESULTS: First, in both sexes and grades the intake from soda drinks was
      significantly higher than the intake from energy drinks. The soda and energy
      drink intake for males was higher than the intake for females; intake for 8th
      graders was higher than this of 10th graders. Second, caffeine intake from soda
      drinks was significantly higher even in those who exceeded the recommended
      maximum caffeine intake. Third, caffeine intakes from soda and energy drinks were
      efficacious in explaining the exceeding of the recommended threshold for daily
      caffeine intake, but the explanatory power of soda drinks was larger.
      CONCLUSIONS: From a caffeine consumption standpoint, health professionals should
      emphasize reduction in both soda and energy drinks.

PMID- 29469618
TI  - Elastic TPU Mesh as Abdominal Wall Inlay Significantly Reduces Defect Size in a
      Minipig Model.
AB  - BACKGROUND: The open abdomen with mesh implantation, followed by early
      reoperation with fascial closure, is a modern surgical approach in difficult
      clinical situations such as severe abdominal sepsis. As early fascial closure is
      not possible in many cases, mesh-mediated fascial traction is helpful for
      conditioning of a minimized ventral hernia after open abdomen. The aim of this
      study was to evaluate the clinical utilization of an innovative elastic
      thermoplastic polyurethane mesh (TPU) as an abdominal wall inlay in a minipig
      model. METHODS: Ten minipigs were divided in two groups, either receiving an
      elastic TPU mesh or a nonelastic polyvinylidene fluoride (PVDF) mesh in inlay
      position of the abdominal wall. After 8 weeks, mesh expansion and abdominal wall
      defect size were measured. Finally, pigs were euthanized and abdominal walls were
      explanted for histological and immunohistochemical assessment. RESULTS: Eight
      weeks after abdominal wall replacement, transversal diameter of the fascial
      defect in the TPU group was significantly smaller than in the PVDF group (4.5 cm
      vs. 7.4 cm; p = 0.047). Immunhistochemical analysis showed increased Ki67
      positive cells (p = 0.003) and a higher number of apoptotic cells (p = 0.047)
      after abdominal wall replacement with a TPU mesh. Collagen type I/III ratio was
      increased in the PVDF group (p = 0.011). CONCLUSION: Implantation of an elastic
      TPU mesh as abdominal wall inlay is a promising approach to reduce the size of
      the ventral hernia after open abdomen by mesh-mediated traction. However, this
      effect was associated with a slightly increased foreign body reaction in
      comparison to the nonelastic PVDF.

PMID- 29469619
TI  - Visual search in unilateral spatial neglect: The effects of distractors on a
      dynamic visual search task.
AB  - The objective of this study was to examine visual scanning performance in
      patients with Unilateral Spatial Neglect (USN) in a visual search task. Thirty
      one right hemisphere stroke patients with USN were recruited. They performed a
      dynamic visual search task with two conditions, with and without distractors,
      while eye movements were monitored with an eye-tracker. The main goal of the task
      was to select target stimuli that appeared from the top of the screen and moved
      vertically downward. Target detection and visual scanning percentage were
      assessed over two hemispaces (right, left) on two conditions (distractor, no
      distractor). Most Scanned Regions (MSR) were calculated to analyze the areas of
      the screen where most points of fixation were directed to. Higher target
      detection rate and visual scanning percentages were found on the right hemispace
      on both conditions. From the MSRs we found that participants with a center of
      attention further to the right of the screen also presented smaller overall MSRs.
      Right hemisphere stroke patients with USN presented not only a significant
      rightward bias but reduced overall search areas, implying hyperattention does not
      only restrict search on the horizontal (right-left) axis but the vertical axis
      (top-bottom) too.

PMID- 29469620
TI  - Dr. Mary Harris Thompson, Pioneer Woman Physicia.

PMID- 29469621
TI  - Radiologic Classification and Imaging Features of Renal Angiomyolipomas According
      to the Amount of Fat.

PMID- 29469622
TI  - The Evolving World of Biomedical Publication: Runaway Train or Merry-Go-Round?

PMID- 29469623
TI  - Reply to "MRI in de Quervain Tenosynovitis: Is Making the Diagnosis Sufficient?"

PMID- 29469624
TI  - Medicolegal-Malpractice and Ethical Issues in RadiologyAn Anonymous Malpractice
      Lawyer Has Asked Me to Be an Expert Witness: Should I Accept?

PMID- 29469625
TI  - MRI in De Quervain Tenosynovitis: Is Making the Diagnosis Sufficient?

PMID- 29469626
TI  - Reply to "Radiologic Evaluation of Intrahepatic Cholangiocarcinoma Perineural
      Invasion".

PMID- 29469627
TI  - Renal Lesions in Lymphangioleiomyomatosis and Tuberous Sclerosis Complex Are
      Rarely Biologically Aggressive.

PMID- 29469628
TI  - Radiologic Evaluation of Intrahepatic Cholangiocarcinoma Perineural Invasion.

PMID- 29469629
TI  - Reply to "Radiologic Classification and Imaging Features of Renal Angiomyolipomas
      According to the Amount of Fat".

PMID- 29469630
TI  - Memorial-Robert Norton Berk.

PMID- 29469631
TI  - Reply to "Renal Lesions in Lymphangioleiomyomatosis and Tuberous Sclerosis
      Complex Are Rarely Biologically Aggressive".

PMID- 29469632
TI  - Hybrid Reconstruction of the Aortic Arch Using a Double-Branched Stent-Graft in a
      Canine Model.
AB  - PURPOSE: To report the results of a hybrid approach to aortic arch repair using
      an innovative unibody double-branched stent graft in a canine model. MATERIALS
      AND METHODS: The stent-graft system consists of two parts: the main body and two
      branches for reconstruction of the supra-arch branches. There is a 2-cm-long
      suturing portion at the proximal end of the main body. Twenty adult German sheep
      dogs underwent a hybrid surgical treatment to place the stent-grafts into the
      proximal descending aorta and the supra-arch branches. Outcomes were assessed by
      operative mortality, complications, imaging studies, and histomorphometric
      analyses. RESULTS: Placement of the stent-graft was performed successfully in all
      dogs without complications. One dog died of respiratory failure due to early
      extubation. The other dogs survived to 6 months without complications, at which
      time they were sacrificed. The mean cardiopulmonary bypass time was 80.3 +/- 7.3
      mins and hypothermic circulatory arrest time was 10.7 +/- 1.9 min. The average
      blood loss was 373.5 mL. At 6 months, postoperative aortic imaging indicated that
      the main body and branches of the stent-graft were fully open and in satisfactory
      position. No migration, deformation, or endovascular leakage was observed.
      Histomorphometric results showed normal arrangement of medial and adventitial
      elastic fibers, moderately proliferated intima, with or without neo-microvessels,
      and microscopic morphological changes in internal elastic lamina. CONCLUSIONS:
      These results demonstrate that it is possible and safe to reconstruct the aortic
      arch with the novel open-branched stent-graft placement.

PMID- 29469633
TI  - Outpatient Addiction Treatment for Problematic Alcohol Use: What Makes Patients
      Who Dropped Out Different from Those Who Did Not?
AB  - BACKGROUND: A minority of individuals with problematic alcohol use effectively
      seek help. Moreover, dropouts from care are not uncommon. It remains a major
      concern for health professionals, as adherence to treatment is significantly
      associated with better physical and psychological outcomes. OBJECTIVES: The main
      aim of this research was to assess what factors could distinguish patients with
      problematic alcohol use who dropped out from those who did not. METHODS: The
      sample included 150 patients followed-up in an outpatient treatment center in
      France for a problematic alcohol use. Two measurement times were planned: at the
      first appointment and after six month of treatment. A large set of individual,
      environmental and institutional variables were considered to compare both
      subgroups. RESULTS: Patients who dropped out mostly differ from patients who did
      not with a higher level of alcohol-related problems, ambivalence, inclinations to
      use the substance, number of missed appointments. Significant results were also
      observed regarding a lower time gap between the first contact with the center and
      the first appointment, as well as the season of the last appointment.
      CONCLUSIONS: Tailored motivational interventions could be offered to ambivalent
      patients, especially during the beginning of the treatment and some significant
      periods of the year. A particular focus should be brought on patients presenting
      such profiles in terms of level of alcohol problems, inclinations to drink and
      motivation to change. Overall, the study provides elements to better understand
      what may bring one patient to drop out of the treatment, and to improve the
      continuity of care.

PMID- 29469634
TI  - Placenta structural changes in heavy smoking mothers: a stereological aspect.
AB  - OBJECTIVE: Smoking during pregnancy is able to alter the structure and function
      of the placenta. In the present study, quantitative changes of the placenta in
      smoking mothers were investigated compared to healthy controls by Cavalieri's
      point counting method. METHODS: Twenty placentas from heavy smoking mothers and
      non-smoker controls (n = 10 in each group) were selected. Systematic uniform
      random sampling (SURS) was used for sample selection and tissue sectioning.
      Quantitative parameters of the placenta in the selected sections were estimated
      after Masson's trichrome staining. Differences between the two groups were
      determined by the Mann Whitney U test and the significance level was set at p <
      .05. RESULTS: Results showed that there was a significant difference in the
      placental weight, total volume of placenta, intervillous space, fibrin and
      syncytiotrophoblast between the heavy smoker group and the control group (p <
      .05). The differences in the volume density of fibrin and blood vessels between
      the smoker and control groups were statistically significant (p < .05).
      CONCLUSIONS: Our findings suggested that quantitative parameters of the placenta
      significantly changed in placentas from the smoker group compared to controls.
      These changes can probably be associated with pregnancy complications in smoking
      mothers and may affect the development and survival of the fetus and even its
      future life.

PMID- 29469635
TI  - In the Experimental Model of Acute Mesenteric Ischemia, The Correlation of Blood
      Diagnostic Parameters with the Duration of Ischemia and their Effects on Choice
      of Treatment.
AB  - : Purpose/Aim: Acute mesenteric ischemia is a syndrome characterized by sudden
      onset abdominal pain followed by intestinal necrosis. Morbidity and mortality
      increase with delayed diagnosis. Even with the latest radiological diagnostic
      methods, early diagnosis and initiation of treatment can be delayed. Using an
      experimental model, here we aim to determine the relationship between the
      laboratory parameters used to detect acute mesenteric ischemia and the duration
      of irreversible ischemia. MATERIALS AND METHODS: A total of 30 male Wistar albino
      rats were divided into five groups, all of which underwent general anesthesia:
      (i) Superior mesenteric artery (SMA) dissection with laparotomy was performed,
      and blood samples and intestinal segment samples were taken after 2 hr (Sham
      group); (ii) volvulus of one-third of the small intestines was performed manually
      by laparotomy, and blood samples and intestinal segment samples were taken after
      2 hr (Volvulus group); (iii) SMA was ligated with laparotomy, and blood samples
      and intestinal segment samples were taken after 2 hr (SMA+ligated 2-hr group);
      (iv) SMA was ligated with laparotomy, and blood samples and intestinal segment
      samples were taken after 4 hr (SMA+ligated 4-hr group); and (v) SMA was ligated
      with laparotomy, and blood samples and intestinal segment samples were taken
      after 6 hr (SMA+ligated 6-hr group). RESULTS: The mean lactate dehydrogenase
      (LDH) activities of the SMA+ligated 2-hr and SMA+ligated 6-hr groups were
      statistically higher than the control group (p = .004). Compared to the Sham and
      Volvulus groups, the mean lactate level of the SMA+ligated 6-hr group was
      significantly higher (p = .004). Compared to the Sham and Volvulus groups, the
      mean D-dimer levels of the SMA+ligated 4-hr and SMA+ligated 6-hr groups were
      significantly higher (p = .004 and .003, respectively). By histopathological
      evaluation, we found that pathological damage increased as the ischemia
      lengthened. CONCLUSIONS: Mesenteric ischemia leads to an irreversible loss of
      intestinal perfusion and an increase in parameters of ischemia. Irreversible
      tissue damage occurs after 4 hr of ischemia and peaks after 6 hr, whereas
      parameters of ischemia (D-dimer, LDH, and L-Lactate levels) are highest at 2 hr
      after the onset of ischemia.

PMID- 29469636
TI  - Total Colpectomy Increases the Risk of Postoperative Hydronephrosis in Vaginal
      Cancer Patients.
AB  - PURPOSE: Due to the rarity of vaginal cancer, surgical treatment results, and
      postoperative complications have been poorly described in the literature. The aim
      of this study was to improve current knowledge about the incidence of
      hydronephrosis following the surgical treatment of vaginal cancer. MATERIALS AND
      METHODS: 32 patients with vaginal cancer of the middle and upper third were
      matched with 32 cervical cancer patients (stages I and II) for comparison of long
      term urological postoperative complications. All patients underwent radical
      surgical treatment and all stage II patients underwent neoadjuvant radiotherapy.
      RESULTS: Hydronephrosis had a significantly higher incidence in the vaginal
      cancer group (p = 0.04), with 14 patients (43.8%) being diagnosed with this
      complication compared to only 5 patients (15.6%) in the cervical cancer group.
      Among patients that received radiotherapy, 40.1% (n = 9) and 22.7% ( = 5) of
      vaginal, respectively cervical cancer patients were found with postoperative
      hydronephrosis. CONCLUSIONS: In vaginal cancer patients total colpectomy
      increases the risk of developing postoperative hydronephrosis, especially if
      neoadjuvant radiotherapy has been applied.

PMID- 29469637
TI  - Mental illness in Sweden (1896-1905) reflected through case records from a local
      general hospital.
AB  - Mental illness in a hospital in a medium-sized town in Sweden was studied.
      Consecutive case records from 1896 to 1905, and also from 2011, were selected. In
      the historical sample, neurasthenia was the most common diagnosis, followed by
      affective disorders and alcohol abuse. ICD-10 diagnoses corresponded well with
      the historical diagnoses. Melancholia resembled modern criteria for depression.
      Mania, insania simplex and paranoia indicated more severe illness. Abuse was more
      common among men and hysteria among women. Those with a medical certificate for
      mental hospital care were very ill and showed no gender difference. There were no
      diagnoses for abuse, but 17% had a high level of alcohol consumption. The pattern
      of signs and symptoms displayed by patients does not appear to change with time.

PMID- 29469638
TI  - Cost comparison of continued anticoagulation with rivaroxaban versus placebo
      based on the 1-year EINSTEIN-Extension trial efficacy and safety results.
AB  - AIMS: The EINSTEIN-Extension trial (EINSTEIN-EXT) found that continued treatment
      with rivaroxaban for an additional 6 or 12 months (vs placebo) after 6-12 months
      of initial anticoagulation significantly reduced the risk of recurrent venous
      thromboembolism (VTE) with a small non-significant increased risk of major
      bleeding (none fatal or in critical site). This study aimed to compare total
      healthcare cost between rivaroxaban and placebo, based on the EINSTEIN-EXT event
      rates. METHODS: Total healthcare cost was calculated as the sum of treatment and
      clinical event costs from a US managed care perspective. Treatment duration and
      event rates were obtained from the EINSTEIN-EXT study. Adjustment on treatment
      duration was made by assuming a 10% non-adherence rate. Drug costs were based on
      wholesale acquisition costs. Cost estimates for clinical events (i.e. recurrent
      deep vein thrombosis [DVT], recurrent pulmonary embolism, major bleeding,
      clinically relevant non-major bleeding) were determined from the literature.
      Results were examined over a +/-20% range of each cost component and over 95%
      confidence intervals (CIs) of event rate differences in deterministic (one-way)
      and probabilistic sensitivity analyses (PSA). RESULTS: Total healthcare cost was
      $1,454 lower for rivaroxaban-treated (vs placebo-treated) patients in the base
      case, with a lower clinical event cost fully offsetting drug cost. The cost
      savings of recurrent DVT alone (-$3,102) was greater than drug cost ($2,723).
      Total healthcare cost remained lower for rivaroxaban in the majority (73%) of PSA
      (cost difference [95% CI] = -$1,454 [-$2,396, $1,231]). LIMITATIONS: This study
      was conducted over the 1-year observation period of the EINSTEIN-EXT trial, which
      limited "real-world" applicability and examination of long-term economic impact.
      Assumptions on drug and clinical event costs were US-based and, thus, not
      applicable to other healthcare systems. CONCLUSIONS: Total healthcare costs were
      estimated to be lower for patients continuing rivaroxaban therapy compared to
      those receiving placebo in VTE patients who had completed 6-12 months of VTE
      treatment.

PMID- 29469640
TI  - Detecting malingering in traumatic brain injury: combining response time with
      performance validity test accuracy.
AB  - OBJECTIVE: The present study examined the incremental utility of item-level
      response time (RT) variables on a traditional performance validity test in
      distinguishing adults with verified TBI from adults coached to feign
      neurocognitive impairment. METHOD: Participants were 45 adults with moderate to
      severe TBI, 45 healthy adults coached to feign neurocognitive impairment (SIM),
      and 61 healthy adult comparisons providing full effort (HC). All participants
      completed a computerized version of the Test of Memory Malingering (TOMM-C) in
      the context of a larger test battery. RT variables examined along with TOMM-C
      accuracy scores included mean RTs (Trial 1, Trial 2, correct and incorrect
      trials) and RT variability indices. RESULTS: Several RT indices differed
      significantly across the groups. In general, SIM produced longer, more variable
      RTs than HC and TBI. Of the RT indices, average RT for Trial 1 and 2 were the
      best predictors of group membership; however, classification accuracies were
      greatly influenced by the groups being compared. Average RT for Trial 1 and 2
      showed excellent discrimination of SIM and HC. All RT indices were less
      successful in discriminating SIM and TBI. Average RT for Trial 1 and 2 added
      incremental predictive value to TOMM-C accuracy in distinguishing SIM from TBI.
      CONCLUSION: Findings contribute to a limited body of research examining the
      incremental utility of combining RT with traditional PVTs in distinguishing
      feigned and bona fide TBI. Findings support the hypothesis that combining RT with
      TOMM-C accuracy can improve its diagnostic accuracy. Future research with other
      groups of clinical interest is recommended.

PMID- 29469639
TI  - Effects of metal oxide nanoparticles on nitrification in wastewater treatment
      systems: A systematic review.
AB  - While the variety of engineered nanoparticles used in consumer products continues
      to grow, the use of metal oxide nanoparticles in electronics, textiles, cosmetics
      and food packaging industry has grown exponentially in recent years, which will
      inevitably result in their release into wastewater streams in turn impacting the
      important biological processes in wastewater treatment plants. Among these
      processes, nitrification play a critical role in nitrogen removal during
      wastewater treatment, however, it is sensitive to a wide range of inhibitory
      substances including metal oxide nanoparticles. Therefore, it is essential to
      systematically asses the effects of metal oxide nanoparticles on nitrification in
      biological wastewater treatment systems. In this review we discuss the present
      scenario of metal oxide nanoparticles and their impact on biological wastewater
      treatment processes, specifically nitrogen removal through nitrification. We also
      summarize the various methods used to measure nitrification inhibition by metal
      oxide nanoparticles and highlight corresponding results obtained using those
      methods. Finally, the key research gaps that need to be addressed in future are
      discussed.

PMID- 29469641
TI  - Castrate-resistant prostate cancer: lessons learnt from a pilot study in the
      palliative care research population.
AB  - BACKGROUND: Palliative care patients are inherently difficult to recruit to and
      retain on studies. Even when patients are recruited, it is hard to complete
      studies with sufficient data. There is a dearth of literature specific to men
      with castrate resistant prostate cancer (CRPC) and the clinical trials
      coordinator/research nurse's perspective in improving trial outcomes in
      palliative care. Objectives To describe the lessons learnt (by the nursing
      research team) from a prospective cohort study of men with CRPC and the practical
      implications for future research in this area. METHODS: A pilot feasibility
      cohort study that followed patients with CRPC from referral until death. The
      participants completed questionnaires while the researcher documented treatments,
      disease status and symptom burden. The recruitment methods, data quality and
      results were analysed. RESULTS AND DISCUSSION: Several lessons have been learnt
      with regard to facilitating trial recruitment and design. These lessons are: the
      importance of building relationships with local urology teams, including all men
      with the diagnosis of CRPC as documented by a medical oncologist or urologist,
      reducing questionnaire burden, capturing symptom scores in clinic, actively
      following up patients by phone, and recording all reasons for drop-out or lost to
      follow-up. These lessons can now be implemented to improve future studies
      involving this demographic.

PMID- 29469642
TI  - Implementing an integrated pathway to care for the dying: is your organisation
      ready?
AB  - BACKGROUND: Integrated pathways for care of the dying aim to promote the delivery
      of high-quality palliative care, regardless of access to specialist services.
      AIM: To produce a heuristic technique to assist with planning and evaluating the
      integration of the care of the dying pathway into everyday work. METHODS:
      Electronic databases were searched to identify research papers focused on the
      implementation of integrated pathways for care of the dying in acute hospital
      settings. RESULTS: A total of 13 articles were reviewed using the four elements
      of normalisation process theory-coherence, cognitive participation, collective
      action and reflexive monitoring. These results informed the development of a
      heuristic for organisational readiness. CONCLUSION: The organisational readiness
      heuristic provides an evidence-based checklist for organisational leaders who are
      planning to introduce new, or evaluate current, integrated pathways for care of
      the dying. The next step is to trial the heuristic for feasibility in practice.

PMID- 29469644
TI  - Research roundup.
AB  - Synopses of a selection of recently published research articles of relevance to
      palliative care.

PMID- 29469643
TI  - Targeted palliative care day therapy interventions using modified MYMOP2 tool can
      improve outcomes for patients with non-malignant diseases.
AB  - BACKGROUND: There is a paucity of evidence supporting the benefits of palliative
      care day therapy services for patients with non-malignant diseases. Outcome
      measures in this setting are also lacking. AIM: To evaluate the use of the
      modified Measure Yourself Medical Outcome Profile 2 (MYMOP2) tool in tailoring
      day therapy services toward the needs of patients with non-malignant conditions
      Method: A single system, 'before and after' design quality improvement study was
      conducted. Data were collected regarding outcome measures, re-referral rates and
      mortality. RESULT: After the introduction of the modified MYMOP2 tool, there was
      an improvement in the mean outcome scores for patients with non-malignant
      disease. Re-referral rates for these patients dropped by 28% during the follow up
      period, with no change in mortality. IMPLICATIONS FOR PRACTICE: These findings
      suggest that using the modified MYMOP2 tool to tailor and measure the outcome of
      holistic day therapy services results in a more sustained improvement for
      patients with non-malignant disease.

PMID- 29469645
TI  - Spirituality among family caregivers in palliative care: an integrative
      literature review.
AB  - BACKGROUND: Family caregivers experience spiritual and existential concerns while
      caring for their terminally ill family members. AIM: To evaluate and synthesise
      studies on spirituality among family caregivers in palliative care. DESIGN: An
      integrative literature review of peer-reviewed articles published between 2000
      and 2016. SAMPLE: Participants were family caregivers (parents, spouses,
      relatives or friends) caring for an adult (age>18 years) family member with a
      terminal illness in a palliative care setting. RESULTS: Data from 26 published
      research papers were systematically analysed. Five themes were identified
      regarding spirituality and family caregiving: a close and meaningful connection,
      spirituality as a way of coping, spiritual needs and expressions among family
      caregivers, spirituality to transcend fears, and spirituality in family
      caregivers' decision-making. IMPLICATIONS FOR PRACTICE: Nurses are encouraged to
      explore the spirituality and spiritual experiences of family caregivers to
      support their spiritual wellbeing while caring for their terminally ill family
      members.

PMID- 29469646
TI  - Politics and palliative care: Republic of the Congo.
AB  - Dion Smyth's review of palliative nursing on the internet.

PMID- 29469647
TI  - How skilled do Israeli nurses perceive themselves to be in providing palliative
      care? Results of a national survey.
AB  - BACKGROUND: In Israel, palliative care (PC) services are limited. This study
      assessed Israeli nurses' perceived competencies and educational needs in
      providing PC. DESIGN: Online administration of the End-of-Life Professional
      Caregiver Survey (EPCS). SETTING/SUBJECTS: Oncology and PC nurses were identified
      through the Israel Ministry of Health and Oncology Nurses' Society. MEASUREMENTS:
      Demographic and practice data were analysed using analysis of variance tests to
      determine differences between nurse characteristics by EPCS domains. RESULTS: The
      sample (n=105) was 94% female, had a mean age of 48 years (SD=10.5) and 83% were
      Jewish Israeli. Thirty-nine percent reported PC training in nursing school and
      42% felt their workplace provided little to no PC education and resources to
      nurses. Those with advanced degrees and those who received post-graduate PC
      training had higher mean scores across EPCS domains (p<0.05 for all).
      CONCLUSIONS: Nursing education and workplace support in PC for Israeli nurses are
      limited. It is hoped that these findings may inform future PC nursing education
      and policy in Israel.

PMID- 29469648
TI  - Imprecise communication and perceptions of palliative care.

PMID- 29469649
TI  - A new way of organising palliative care for patients with severe chronic
      obstructive pulmonary disease.
AB  - Patients with chronic obstructive pulmonary disease (COPD) often live with unmet
      palliative needs and low quality of life, although several guidelines recommend
      that those with COPD should be offered early and integrated palliative care.
      However, none of the guidelines describe how these recommendations can be
      operationalised and the current literature offers little information about
      experiences with developing and implementing new palliative care services. This
      article offers insight into the experience of developing and implementing a new
      palliative outpatient structure for patients with severe COPD. All patients are
      assigned to a nurse who has overall responsibility for establishing and
      maintaining an individualised relationship with the patient and identifying their
      needs for care and treatment. Routine outpatient visits are replaced by ad hoc
      consultations, and patients are seen by pulmonary specialists only when there is
      a need for medical assessment and treatment or a planned advanced care planning
      dialogue. The new service was succesfully implemented; however, the changes
      required good multidisciplinary collaboration, dedicated health professionals and
      managerial support. This paper highlights the need for further studies to
      investigate the effectiveness of new palliative care interventions for patients
      with COPD.

PMID- 29469651
TI  - "I'm Scared of the Disappointment": Young Adult Smokers' Relational Identity Gaps
      and Management Strategies as Sites of Communication Intervention.
AB  - While cigarette smoking is decreasing among young adults, rates of nicotine
      consumption through other devices, most notably electronic cigarettes, are on the
      rise. Framed by communication theory of identity, this study examines young adult
      smokers' experiences with relational others in regard to their smoking. Focus
      group discussions and individual interviews convened with 20 young adult
      cigarette and electronic cigarette smokers revealed identity gaps implicating the
      relational layer of identity, including personal-relational, enacted-relational,
      and personal-enacted-relational identity gaps. Participants used communicative
      and behavioral strategies to manage relational discrepancies. The documented
      identity gaps and management strategies present opportunities for targeted
      smoking cessation interventions that amplify dissonance created through identity
      gaps as a motivational tactic.

PMID- 29469652
TI  - Effects of the ammonium loading rate on nitrite-oxidizing activity during
      nitrification at a high dose of inorganic carbon.
AB  - In this study, the effects of the ammonium loading rate (ALR) and inorganic
      carbon loading rate (ILR) on the nitrification performance and composition of a
      nitrifying bacterial community were investigated in a moving bed biofilm reactor,
      using poly(vinyl alcohol) (PVA) sponge cubes as a supporting carrier. Between the
      two ALRs of 0.36 and 2.16 kg-N m-1 d-1, stable partial nitritation was achieved
      at the higher ALR. Inorganic carbon was dosed at high levels: 33.1, 22.0, 16.4,
      11.0, and 5.4 times the theoretical amount. Nonetheless, nitrification efficiency
      was not affected by the ILR at the two ALRs. Quantitative PCR analysis of ammonia
      and nitrite-oxidizing bacteria revealed that ALR is an important determinant of
      partial nitritation by accumulating ammonia-oxidizing bacteria in the
      nitrification system. In comparison, two nitrite-oxidizing bacterial genera
      (Nitrobacter and Nitrospira) showed almost the same relative abundance at various
      ALRs and ILRs. Terminal restriction fragment length polymorphism targeting the
      gene of ammonia monooxygenase subunit A revealed that Nitrosomonas europaea
      dominated under all conditions.

PMID- 29469650
TI  - Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis.
AB  - BACKGROUND: Conditions of excess androgen in women, such as polycystic ovary
      syndrome (PCOS), often exhibit intergenerational transmission. One way in which
      the risk for PCOS may be increased in daughters of affected women is through
      exposure to elevated androgens in utero. Hyperandrogenemic conditions have
      serious health consequences, including increased risk for hypertension and
      cardiovascular disease. Recently, gut dysbiosis has been found to induce
      hypertension in rats, such that blood pressure can be normalized through fecal
      microbial transplant. Therefore, we hypothesized that the hypertension seen in
      PCOS has early origins in gut dysbiosis caused by in utero exposure to excess
      androgen. We investigated this hypothesis with a model of prenatal androgen (PNA)
      exposure and maternal hyperandrogenemia by single-injection of testosterone
      cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then
      completed a gut microbiota and cardiometabolic profile of the adult female
      offspring. RESULTS: The metabolic assessment revealed that adult PNA rats had
      increased body weight and increased mRNA expression of adipokines: adipocyte
      binding protein 2, adiponectin, and leptin in inguinal white adipose tissue.
      Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA
      animals. The fecal microbiota profile of PNA animals contained higher relative
      abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and
      Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus,
      Clostridium. The PNA animals also had an increased relative abundance of bacteria
      associated with biosynthesis and elongation of unsaturated short chain fatty
      acids (SCFAs). CONCLUSIONS: We found that prenatal exposure to excess androgen
      negatively impacted cardiovascular function by increasing systolic and diastolic
      blood pressure and decreasing heart rate. Prenatal androgen was also associated
      with gut microbial dysbiosis and altered abundance of bacteria involved in
      metabolite production of short chain fatty acids. These results suggest that
      early-life exposure to hyperandrogenemia in daughters of women with PCOS may lead
      to long-term alterations in gut microbiota and cardiometabolic function.

PMID- 29469653
TI  - Analytical similarity assessment of rituximab biosimilar CT-P10 to reference
      medicinal product.
AB  - CT-P10 (TruximaTM) was recently approved as the world's first rituximab
      biosimilar product in the European Union (EU) and South Korea. To demonstrate
      biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3
      way similarity assessment has been conducted between CT-P10, EU-Rituximab and US
      Rituximab, focusing on the physicochemical and biological quality attributes. A
      multitude of state-of-the-art analyses revealed that CT-P10 has identical primary
      and higher order structures compared to the original product. Purity/impurity
      profiles of CT-P10 measured by the levels of aggregates, fragments, non
      glycosylated form and process-related impurities were also found to be comparable
      with those of RMPs. In terms of the post-translational modification, CT-P10
      contains slightly less N-terminal pyro-glutamate variant, which has been known
      not to affect product efficacy or safety. Oligosaccharide profiling has revealed
      that, although CT-P10 contains the same conserved glycan species and relative
      proportion with the RMPs, the content of total afucosylated glycan in CT-P10 was
      slightly higher than in EU- or US-Rituximab. Nevertheless, the effect of the
      observed level of afucosylation in CT-P10 drug product on Fc receptor binding
      affinity or antibody-dependent cell-mediated cytotoxicity was found to be
      negligible based on the spiking study with highly afucosylated sample. Arrays of
      biological assays representative of known and putative mechanisms of action for
      rituximab have shown that biological activities of CT-P10 are within the quality
      range of RMPs. Recent results of clinical studies have further confirmed that the
      CT-P10 exhibits equivalent clinical efficacy and safety profiles compared to EU-
      and US-Rituximab. The current 3-way similarity assessment together with clinical
      study results confidently demonstrate that CT-P10 is highly similar with EU- and
      US-Rituximab in terms of physicochemical properties, biological activities,
      efficacy, and safety for its final approval as a biosimilar product.

PMID- 29469654
TI  - The effect of pre-exercise ingestion of corinthian currant on endurance
      performance and blood redox status.
AB  - The present study investigated the effect of Corinthian currant pre-exercise
      supplementation on metabolism, performance and blood redox status during, and
      after prolonged exercise. Eleven healthy participants (21-45y) performed a 90-min
      constant-intensity (60-70% VO2max) submaximal-trial, plus a time-trial (TT) to
      exhaustion (95% VO2max) after consuming an isocaloric (1.5g CHO/kg BM) amount of
      randomly assigned Corinthian currant or glucose-drink, or water (control). Blood
      was drawn at baseline, pre-exercise, 30min, 60min, 90min of submaximal-trial,
      post-TT, and 1h post-TT. Post-ingestion blood glucose (GLU) under Corinthian
      currant was higher compared with water, and similar compared with glucose-drink
      throughout the study. Respiratory quotient under Corinthian currant was similar
      with glucose-drink and higher than water throughout the submaximal trial.
      Accordingly, higher CHO and lower fat oxidation were observed under Corinthian
      currant compared with water. The TT performance was similar between Corinthian
      currant, glucose-drink and water. Redox status were similar under all three
      conditions. Reduced glutathione (GSH) declined while total antioxidant capacity
      (TAC) and uric acid increased during exercise. GSH and TAC returned to baseline,
      while uric acid remained increased the following 1h. Corinthian currant, although
      did not alter exercise-mediated redox status changes and performance, was equally
      effective to a glucose-drink in maintaining GLU levels during prolonged cycling.

PMID- 29469655
TI  - Valentin Magnan and Sergey Korsakov: French and Russian pioneers in the study of
      alcohol abuse.
AB  - This study focuses on two outstanding psychiatrists: the Frenchman Valentin
      Magnan (1835-1916) and the Russian Sergey Korsakov (1854-1900). Their
      international renown is primarily associated with their investigations into
      health consequences of alcohol consumption; they were pioneers in this field, and
      happened to know each other well. The similarities and differences are shown in
      social and scientific approaches adopted by these two scientists. In his work,
      Magnan focused mainly on absinthe and epilepsy; he considered alcoholism to be a
      hereditary mental disorder. Korsakov, after a period of work in Paris under
      Magnan's guidance, represented a more modern generation and was advancing
      fundamental ideas on the nature of psychoses and merging clinical features,
      somatic, psychological, and social factors. Although Magnan has practically
      disappeared from the current literature on alcoholism, Korsakov is still clearly
      present today.

PMID- 29469656
TI  - When the Teacher Becomes the Pupil: Lessons Derived from a Terminally Ill
      Student.

PMID- 29469660
TI  - Corrigendum.

PMID- 29469661
TI  - Biological Evidence Regarding Psychopathy Does Not Affect Mock Jury Sentencing.
AB  - Research on the biological factors influencing criminal behavior is increasingly
      being introduced into court, necessitating research on how such evidence is
      perceived and influences decision makers. Research on how this evidence
      influences sentencing recommendations is inconclusive. In this study, we focus on
      biological evidence related to psychopathy, a construct commonly associated with
      criminal behavior. Approximately 800 community members were presented with a case
      vignette detailing an individual who is described as having a high level of
      psychopathic traits. Participants received either psychological information about
      psychopathy (i.e., no biological evidence), evidence the defendant had genetic
      risk factors for psychopathy, or written neuroimaging evidence the defendant had
      brain deficits associated with psychopathy. Participants then recommended a
      sentence. Overall, recommended sentence lengths did not differ between evidence
      conditions. These findings add to a growing body of research suggesting that
      biological evidence may not have as much of an influence on jurors as previously
      thought.

PMID- 29469663
TI  - A Neuroscience-Oriented Research Approach to Borderline Personality Disorder.
AB  - Traditionally, the study of personality disorders had been based on
      psychoanalytic or behavioral models. Over the past two decades, there has been an
      emerging neuroscience model of borderline personality disorder (BPD) grounded in
      the concept of BPD as a condition in which dysfunctional neural circuits underlie
      its pathological dimensions, some of which include emotion dysregulation (broadly
      encompassing affective instability, negative affectivity, and hyperarousal),
      abnormal interpersonal functioning, and impulsive aggression. This article,
      initiated at a joint Columbia University-Cornell University Think Tank on BPD
      with representation from the Icahn School of Medicine at Mount Sinai, suggests
      how to advance research in BPD by studying the dimensions that underlie BPD in
      addition to studying the disorder as a unitary diagnostic entity. We suggest that
      linking the underlying neurobiological abnormalities to behavioral symptoms of
      the disorder can inform a research agenda to better understand BPD with its
      multiple presentations.

PMID- 29469664
TI  - Mentalization in Adolescents With Borderline Personality Disorder: A Comparison
      With Healthy Controls.
AB  - Mentalization is proposed to underlie the disturbed interpersonal relatedness
      that is a hallmark of borderline personality disorder (BPD). Despite growing
      evidence of BPD in adolescents, studies examining mentalization in relation to
      adolescent BPD have remained limited. Given contradictory findings of this
      relationship, particularly with adults, further research of mentalization in
      adolescents with BPD is warranted. The current study further clarifies the nature
      of mentalizing impairments, related to BPD, by examining different aspects of
      mentalization between adolescents with BPD (n = 26) and a group of healthy
      controls (n = 25). Findings support studies that suggest that mentalization may
      be an important treatment target, influencing BPD symptoms and interpersonal
      functioning in adolescents with BPD. They also support the importance of
      examining mentalizing abilities in relation to varying levels of complexity,
      interpersonal contexts, and levels of arousal. Limitations and further research
      are discussed.

PMID- 29469662
TI  - A Recurrent Question: What Is Borderline?
AB  - The status of borderline personality disorder (BPD) as a diagnostic category is a
      matter of continuing controversy. In the United States, BPD is one of the most
      frequent diagnoses of psychiatric inpatients, and a similar tendency emerges in
      Europe. Nearly all theoretical aspects of BPD have been questioned, including its
      very position as a personality disorder. In this article, we trace the evolution
      of the borderline concept from the beginning of the 20th century to the current
      psychometric research. We argue that the status of BPD is fraught with conceptual
      difficulties, including an unrecognized semantic drift of major phenomenological
      terms (e.g., identity), a lack of general principles for the distinction of BPD
      and the major psychiatric syndromes (e.g., schizophrenia spectrum disorders), and
      insufficient definitions of key nosological concepts. These difficulties
      illustrate general problems in today's psychiatry that require consideration.

PMID- 29469657
TI  - Direct mass spectrometric characterization of disulfide linkages.
AB  - Disulfide linkage is critical to protein folding and structural stability. The
      location of disulfide linkages for antibodies is routinely discovered by
      comparing the chromatograms of the reduced and non-reduced peptide mapping with
      location identification confirmed by collision-induced dissociation (CID) mass
      spectrometry (MS)/MS. However, CID product spectra of disulfide-linked peptides
      can be difficult to interpret, and provide limited information on the backbone
      region within the disulfide loop. Here, we applied an electron-transfer
      dissociation (ETD)/CID combined fragmentation method that identifies the
      disulfide linkage without intensive LC comparison, and yet maps the disulfide
      location accurately. The native protein samples were digested using trypsin for
      proteolysis. The method uses RapiGest SF Surfactant and obviates the need for
      reduction/alkylation and extensive sample manipulation. An aliquot of the digest
      was loaded onto a C4 analytical column. Peptides were gradient-eluted and
      analyzed using a Thermo Scientific LTQ Orbitrap Elite mass spectrometer for the
      ETD-triggered CID MS 3 experiment. Survey MS scans were followed by data
      dependent scans consisting of ETD MS2 scans on the most intense ion in the survey
      scan, followed by 5 MS3 CID scans on the 5 most intense ions in the ETD MS2 scan.
      We were able to identify the disulfide-mediated structural variants A and A/B
      forms and their corresponding disulfide linkages in an immunoglobulin G2
      monoclonal antibody with lambda light chain (IgG2lambda), where the location of
      cysteine linkages were unambiguously determined.

PMID- 29469665
TI  - Psychopathy and Internalizing Psychopathology: A Triarchic Model Perspective.
AB  - Methodological and conceptual differences across studies have impeded our
      understanding of the relationship between psychopathy and internalizing
      psychopathology. To shed further light on this question, we undertook
      correlational and structural-modeling analyses of data from two samples to
      characterize how facets of psychopathy relate to internalizing psychopathology
      when assessed using multidimensional measures of each construct (i.e., Triarchic
      Psychopathy Measure, Inventory of Depression and Anxiety Symptoms). Participants
      for Study 1 were 470 undergraduates and community-dwelling adults who completed
      these measures in self-report form; participants for Study 2 were 301 community
      dwelling adults who completed informant-rating versions of these measures (as
      applied to a known-other). Across samples, analyses revealed sharply contrasting
      associations for the three triarchic-model facets with internalizing
      psychopathology and its subdomains, with boldness relating negatively in most
      cases, disinhibition relating positively in most cases, and meanness exhibiting
      mostly null associations. Results provide a nuanced picture of associations
      between psychopathic symptomatology and internalizing problems.

PMID- 29469658
TI  - Evolving Treatment Patterns of NFL Players by Orthopaedic Team Physicians Over
      the Past Decade, 2008-2016.
AB  - BACKGROUND: Previous studies have analyzed the treatment patterns used to manage
      injuries in National Football League (NFL) players. HYPOTHESIS: Treatment
      patterns for injuries in NFL players will have changed over the study period.
      STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 5.
      METHODS: The head orthopaedic team physicians for all 32 NFL teams were asked to
      complete a survey containing questions regarding experience as team physician,
      medical coverage of the team, and treatment preferences for some of the most
      common injuries occurring in football players. Responses from the current survey
      were compared with responses from the same survey sent to NFL team physicians in
      2008. RESULTS: Responses were received from 31 (31/32, 97%) NFL team physicians
      in 2008 and 29 (29/32, 91%) NFL team physicians between April 2016 and May 2017.
      The proportion of physicians preferring patellar tendon autograft in anterior
      cruciate ligament (ACL) reconstruction increased from 87% in 2008 to 97% in 2016
      ( P = 0.054). In 2008, 49% of physicians allowed return to contact after ACL
      reconstruction at 6 months or less as compared with only 14% of physicians in
      2016 ( P = 0.033). In 2008, 93% of physicians used Toradol injections prior to a
      game to help with nagging injuries. Toradol injection utilization decreased to
      48% of physicians in 2016 ( P < 0.001). Seventy-nine percent of physicians would
      administer 5 or more Toradol injections prior to a game in 2008, as compared with
      28% of physicians in 2016 ( P < 0.0001). CONCLUSION: Orthopaedic physicians have
      changed their injury treatment preferences for professional football players. In
      particular, physicians have become more cautious with allowing players to return
      to play after ACL reconstruction and with the use of pregame Toradol injections.
      CLINICAL RELEVANCE: Expert opinions can help guide treatment decisions and lead
      to better care of all athletes.

PMID- 29469659
TI  - Grading of oligodendroglial tumors of the brain with apparent diffusion
      coefficient, magnetic resonance spectroscopy, and dynamic susceptibility contrast
      imaging.
AB  - Purpose We explored whether advanced magnetic resonance (MR) imaging techniques
      could grade oligodendrogliomas. Methods Forty patients (age 9-61 years) with
      oligodendroglial tumors were selected. There were 23 patients with World Health
      Organization grade II (group 1) and 17 patients with grade III (group 2) tumors.
      Apparent diffusion coefficient (ADC) maps were calculated by b values of 0 and
      1000 s/mm2. Dynamic susceptibility contrast (DSC) images were obtained during the
      first pass of a bolus of gadolinium-based contrast. These data were post
      processed and cerebral blood volume (CBV) maps and permeability (PS) were
      calculated. MR spectroscopy was acquired after drawing a region of interest on
      the tumor using two-dimensional chemical shift imaging. Statistical analysis was
      performed using SPSS software. Results When the rPSmax was combined with the
      rCBVmax, there was a significant difference between the two groups ( p <= 0.03)
      with area under the curve of 0.742 (95% CI: 0.412-0.904). rCBV, rADC,
      choline/creatine, and choline/NAA alone were able to differentiate between the
      two groups; however, they did not show any statistical difference with p values
      of <= 0.121, <= 0.722, and <= 0.582, respectively. A CBV PS product threshold of
      0.53 provided a sensitivity of 80% and a specificity of 83.3% in detection of
      grade III tumors. Conclusion Combined rCBVmax and rPSmax can be utilized to grade
      oligodendrogliomas. ADC values, relative cerebral blood volume (rCBV), and MR
      spectroscopy alone can be utilized to differentiate between the two groups of
      oligodendrogliomas but without statistical significance.

PMID- 29469666
TI  - The DSM-5 Trait Measure in a Psychiatric Sample of Late Adolescents and Emerging
      Adults: Structure, Reliability, and Validity.
AB  - The inclusion of a dimensional trait model of personality pathology in DSM-5
      creates new opportunities for research on developmental antecedents of
      personality pathology. The traits of this model can be measured with the
      Personality Inventory for DSM-5 (PID-5), initially developed for adults, but also
      demonstrating validity in adolescents. The present study adds to the growing body
      of literature on the psychometrics of the PID-5, by examining its structure,
      validity, and reliability in 187 psychiatric-referred late adolescents and
      emerging adults. PID-5, Big Five Inventory, and Kidscreen self-reports were
      provided, and 88 non-clinical matched controls completed the PID-5. Results
      confirm the PID-5's five-factor structure, indicate adequate psychometric
      properties, and underscore the construct and criterion validity, showing
      meaningful associations with adaptive traits and quality of life. Results are
      discussed in terms of the PID-5's applicability in vulnerable populations who are
      going through important developmental transition phases, such as the step towards
      early adulthood.

PMID- 29469667
TI  - 10-Year Outcome of Suicidal Behavior in Borderline Personality Disorder.
AB  - Prospective predictors of suicide attempts were assessed in 118 subjects with
      borderline personality disorder (BPD) after 10 or more years of follow-up. Mean
      (SD) time to follow-up was 14.4 (4.7) years. Subjects were predominately female
      (78.8%), Caucasian (81.4%), and of lower socioeconomic status. Initial
      recruitment was evenly balanced between inpatient, outpatient, and non-patient
      (community) sources. In the 10-year interval, 55 subjects (46.6%) attempted
      suicide. Compared to baseline, suicidal ideation, number of attempts, and non
      suicidal self-injury diminished markedly. Core symptoms of BPD, substance abuse,
      and alcohol use disorders decreased significantly; however, major depressive
      disorder (MDD) remained constant at 50%. Forty-four percent of subjects had poor
      psychosocial, vocational, and economic outcomes. Psychosocial outcome was
      independent of suicide history and any treatment. Increased risk was associated
      with interval hospitalization prior to any attempt (illness severity), as well as
      poor social, vocational, and psychosocial functioning at baseline.

PMID- 29469669
TI  - "I Want to Walk with My Moko." The Application of Social Cognitive Theory in the
      Creation of a Diabetes Prevention Documentary with New Zealand Maori.
AB  - Type 2 diabetes is almost three times more prevalent in the indigenous people of
      New Zealand (Maori) than non-Maori. Despite the high rate of diabetes there is a
      low level of diabetes knowledge and awareness in the Maori community. Several
      studies of Maori health identify a need for new health communication approaches
      to diabetes prevention in order to reduce the gap between Maori and non-Maori
      disease rates. We applied a Community-Based Participatory Research (CBPR)
      framework and behavioral theory to create a culturally appropriate documentary
      for Maori at risk for type 2 diabetes. We discuss how we utilized Bandura's
      social cognitive theory to provide a culturally sensitive theoretical basis for
      behavior change messaging. We outline why social cognitive theory was a
      culturally appropriate foundation and describe the role of the community in
      shaping the documentary messaging. A culture-centered approach utilizing
      participatory methodologies and culturally sensitive behavioral change theory
      might serve as a model for creating health communication resources in
      collaboration with other indigenous communities.

PMID- 29469668
TI  - Review of de novo cerebral arteriovenous malformation: haemorrhage risk,
      treatment approaches and outcomes.
AB  - Objective A small number of patients has been reported to develop a completely
      new or de novo arteriovenous malformation (AVM) after brain surgery, haemorrhage,
      head trauma or ischaemic stroke. The natural history of these lesions is unknown.
      In this review, both ruptured and unruptured de novo AVMs and their treatments
      were reviewed. Methods Published literature in the PubMed database citing 'de
      novo cerebral arteriovenous malformation' was reviewed. Additional studies were
      identified through reference searches in each reviewed article. A review was
      performed using all published cases, the treatment approaches and outcomes.
      Results A total of 38 patients, including 37 de novo AVMs reported from 1988 to
      17 November 2017 and our one patient, was collected. The age at AVM diagnosis was
      5-73 years (mean +/- SD, 27.6 +/- 20.5 years). The duration time, from negative
      examination to AVM diagnosis, was 2 months to 25 years (mean +/- SD, 6.6 +/- 4.9
      years). The presentation of de novo AVM was headaches in three (7.9%) patients,
      bleedings in 12 (31.6%), incidental in 14 (36.8%) and seizure in nine (23.7%).
      The estimated risk of haemorrhage was 4.8% per year. Seventeen (44.7%) patients
      were treated with surgical resection, 10 (26.3%) were conservatively observed,
      nine (23.7%) were treated with radiosurgery and two (5.3%) were endovascularly
      embolised. The morbidity and mortality were reported as 5.3% and 7.9%,
      respectively. Conclusion Post-natal de novo AVMs have been reported. Their annual
      haemorrhage risk is 4.8%. Most of them are treated by surgical resection and are
      associated with morbidity and mortality.

PMID- 29469670
TI  - Role of miRNAs in treatment response and toxicity of childhood acute
      lymphoblastic leukemia.
AB  - Childhood acute lymphoblastic leukemia survival rates have increased remarkably
      during last decades due, in part, to intensive treatment protocols. However,
      therapy resistance and toxicity are still two important barriers to survival. In
      this context, pharmacoepigenetics arises as a tool to identify new predictive
      markers, required to guide clinicians on risk stratification and dose
      individualization. The present study reviews current evidence about miRNA
      implication on childhood acute lymphoblastic leukemia therapy resistance and
      toxicity. A total of 12 studies analyzing differential miRNA expression in
      relation to drug resistance and six studies exploring the association between
      miRNAs-related SNPs and drug-induced toxicities were identified. We pointed out
      to miR-125b together with miR-99a and/or miR-100 overexpression as markers of
      vincristine resistance and rs2114358 in mir-1206 as mucositis marker as the most
      promising results.

PMID- 29469671
TI  - Patient perspectives following pharmacogenomics results disclosure in an
      integrated health system.
AB  - AIM: To assess patient perceptions and utilization of pharmacogenomics (PGx)
      testing in an integrated community health system. METHODS: Fifty-seven patients
      completed an online survey assessing their experiences with PGx testing offered
      through two methods: a designated PGx clinic or direct access in-home testing.
      RESULTS: The majority of participants perceived PGx testing as helpful in their
      healthcare and reported understanding their results. Some had concerns about
      privacy and discrimination; most lacked familiarity with the Genetic Information
      Nondiscrimination Act. There were no significant differences in views between
      participants tested through either model. CONCLUSION: Participants reported value
      in both methods of PGx testing. Patient experiences, understanding and result
      utilization will play an important role in informing future development and
      implementation of PGx programs.

PMID- 29469672
TI  - VA Staff Perceptions of Barriers and Facilitators to Home-and Community-Based
      Placement Post-Hospital Discharge.
AB  - This study identifies factors U.S. Department of Veterans Affairs (VA) staff
      perceived to promote or impede home- and community-based services (HCBS)
      placement post-hospital discharge among Veterans cared for within the VA. Data
      derive from 35 semi-structured interviews with staff from 12 VA medical centers
      from around the country. VA staff reported that Veteran's care needs and social
      and financial resources influence HCBS placement. They also reported
      prerequisites for successful placement, including housing, unpaid informal care,
      and non-VA services funded privately and by public programs such as Medicaid and
      the Older Americans Act. Lack of staffing and failure to offer the specific types
      of services needed limit referral to and use of HCBS. Budgetary imperatives
      influence the relative availability of HCBS across VA medical centers. Findings
      highlight patient-, provider-, and system-level constraints that impede
      successful placement at home and in the community of Veterans in need of long
      term services and supports after hospitalization.

PMID- 29469673
TI  - Forgiveness, Depression, and Suicidal Behavior in Adolescents: Gender Differences
      in this Relationship.
AB  - With the development of positive psychology, protective factors have received
      increased attention as buffers against suicidal ideation and attempts and against
      the risk factors for suicide (e.g., depressive symptoms). Empirical evidence
      suggests that one of the protective factors associated with depression and
      suicide is forgiveness. Although previous studies have demonstrated a negative
      association between forgiveness and risk of suicide, studies on gender
      differences in adolescents are still scarce. Thus, the authors assessed the
      moderating role of gender in a sample of adolescents. The participants were 572
      adolescents (50.9% boys; M age = 15.49 years, SD = 1.09 years) from secondary
      school centers. The results revealed that forgiveness moderated the relationship
      between depression and suicidal ideation for boys but not for girls.
      Specifically, for boys the relationship between depression and suicidal thoughts
      and behaviors weakened as levels of forgiveness increased. These findings suggest
      therapeutic applications to reduce the likelihood of suicide in the group of
      adolescent boys with higher scores on depression and lower levels of forgiveness.
      The study results are discussed in terms of the need to use gender perspectives
      in positive psychology intervention programs.

PMID- 29469674
TI  - Governance, Accountability, and Organizational Development: Eldercare Unit
      Managers' and Local Politicians' Experiences of and Responses to State
      Supervision of Swedish Eldercare.
AB  - This article explores how local politicians and care unit managers in Swedish
      eldercare experience and respond to state supervision (SSV). Twelve politicians
      and twelve managers in 15 previously inspected municipalities were interviewed
      about their experiences of and reactions to SSV in relation to their views of
      care quality and routines in eldercare practice. The findings indicate that local
      managers and political chairs perceived SSV in eldercare positively at a
      superficial level but were critical of and disappointed with specific aspects of
      it. In terms of (a) governance, chairs and managers said SSV strengthened
      implementation of national policies via local actors, but they were critical of
      SSV's narrow focus on control and flaws in eldercare practice. With regard to (b)
      accountability, SSV was seen as limited to accountability for finances and
      systemic performance, and regarding (c) organizational development, SSV was seen
      as limited to improving routines and compliance with legislation, while local
      definitions of quality are broader than that. In general, local actors regarded
      SSV as improving administrative aspects and routines in practice but ignoring the
      relational content of eldercare quality.

PMID- 29469675
TI  - Lessons from the Past: Some Histories of Alpha-1 Antitrypsin Deficiency Before
      Its Discovery.
AB  - A1AT deficiency- a genetically inherited autosomal codominant disease with more
      than 120 identified alleles- was first identified by Laurell and Eriksson in
      1963. The most common hereditary disorder in adults, A1AT causes an increased
      risk of developing pulmonary emphysema and liver disease. In A1AT patients, lung
      disease generally presents at a younger age than "usual" chronic obstructive
      pulmonary disease (COPD) and it may be misdiagnosed as asthma. Because A1AT
      deficiency patients can show the same clinical features as non-deficient COPD
      (including increased evidence of bronchiectasis, frequent exacerbations, impaired
      health status and a degree of reversibility of airflow obstruction), the World
      Health Organization recommend to test every patient with a diagnosis of COPD or
      adult-onset asthma for A1AT deficiency. Despite these recommendations, the
      epidemiology of A1AT deficiency remains uncertain. Although recently discovered
      A1AT deficiency has affected human populations since antiquity. By using
      scientific data and recently studied skeletons and historical cases, we show that
      it is now possible to reconstruct the natural history of pathological processes,
      whether due to genetic, infectious or environmental factors. We believe that the
      evolution of disease in patients and research to elucidate the relationship
      between social science and environmental are pertinent contemporaneous subjects.

PMID- 29469676
TI  - The Glittre-ADL Test Cut-Off Point to Discriminate Abnormal Functional Capacity
      in Patients with COPD.
AB  - The study objective was to determine a cut-off point for the Glittre activities
      of daily living (ADL)test (TGlittre) to discriminate patients with normal and
      abnormal functional capacity. Fifty-nine patients with moderate to very severe
      COPD (45 males; 65 +/- 8.84 years; BMI: 26 +/- 4.78 kg/m2; FEV1: 35.3 +/- 13.4%
      pred) were evaluated for spirometry, TGlittre, 6-minute walk test (6 MWT),
      physical ADL, modified Medical Research Council scale (mMRC), BODE index, Saint
      George's Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT). The
      receiver operating characteristic (ROC) curve was used to determine the cut-off
      point for TGlittre in order to discriminate patients with 6 MWT < 82% pred. The
      ROC curve indicated a cut-off point of 3.5 minutes for the TGlittre (sensitivity
      = 92%, specificity = 83%, and area under the ROC curve = 0.95 [95% CI: 0.89
      0.99]). Patients with abnormal functional capacity had higher mMRC (median
      difference 1 point), CAT (mean difference: 4.5 points), SGRQ (mean difference:
      12.1 points), and BODE (1.37 points) scores, longer time of physical activity
      <1.5 metabolic equivalent of task (mean difference: 47.9 minutes) and in sitting
      position (mean difference: 59.4 minutes) and smaller number of steps (mean
      difference: 1,549 minutes); p < 0.05 for all. In conclusion, the cut-off point of
      3.5 minutes in the TGlittre is sensitive and specific to distinguish COPD
      patients with abnormal and normal functional capacity.

PMID- 29469677
TI  - Spirometric Criteria for Chronic Obstructive Pulmonary Disease in Clinical Trials
      of Pharmacotherapy.
AB  - Clinical trials of pharmacotherapy in chronic obstructive pulmonary disease
      (COPD) often include older persons with moderate-to-severe airflow-obstruction,
      as defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD).
      In this context, spirometric airflow-obstruction establishes COPD. Because GOLD
      misidentifies COPD and its severity in older persons, we set out to apply more
      age-appropriate spirometric criteria from the Global Lung function Initiative
      (GLI) in a prior clinical trial of COPD pharmacotherapy, specifically the Towards
      a Revolution in COPD Health (TORCH) trial - N = 6,112, mean age 65 years. In the
      TORCH trial, which enrolled GOLD-defined moderate COPD (26.2%, n = 1,200) and
      GOLD-defined severe COPD (73.8%, n = 4,511), the GLI reclassification yielded a
      higher frequency of severe COPD (89.6%, n = 5,474), the inclusion of restrictive
      pattern (6.9%, n = 420) and, in turn, a very low frequency of moderate COPD
      (3.5%, n = 212). These GLI reclassification results suggest that GOLD-based
      enrollment criteria for the TORCH trial may have assembled a cohort that was: 1)
      less likely to respond to COPD pharmacotherapy, given the greater representation
      of severe COPD, very minor representation of moderate COPD, and inclusion of a
      non-obstructive spirometric impairment (restrictive-pattern); and 2) more likely
      to have medication-related adverse events, given the inappropriate use of COPD
      pharmacotherapy in misidentified COPD (restrictive-pattern). We therefore propose
      that future clinical trials of COPD pharmacotherapy should consider GLI criteria
      for defining COPD, including a greater representation of GLI-defined moderate
      COPD.

PMID- 29469678
TI  - Delayed diagnosis of an intraorbital wooden foreign body.
AB  - A 35-year-old male patient was presented with pain on his right upper eyelid. A
      piece of wood injured his orbital and supraorbital regions while working at a
      furniture factory 10 days prior to our hospital admission. It was learned that
      the patient was discharged following the primary would closure procedure.
      Subsequent to the craniofacial computed tomography, primary wound closure was
      performed in the emergency room of previous hospital. In our clinic, a skin
      suturing on the nasal side of the right eyebrow was inspected and a foreign body
      (FB) was palpated on the superonasal contiguity of the patients' right globe. A
      hyperdense FB measuring 30 * 10 * 5 mm in size with smooth margins on superonasal
      contour of the globe was detected. Superonasal orbitotomy was performed and the
      FB was completely removed. Finally, visual acuity was 20/20 and a mild residual
      ptosis was observed.

PMID- 29469679
TI  - Gabrielle Levy and the Roussy-Levy syndrome.
AB  - In 1934, Gabrielle Levy died at the age of 48. She became well known for an
      article she published on a hereditary polyneuropathy in cooperation with Gustav
      Roussy, resulting in the eponym Roussy-Levy syndrome. Not much is known about
      this extraordinary neurologist/neuropathologist. Her family declared that she
      died from the disease she was studying. She was a pupil of Pierre Marie, with
      whom she worked at the Salpetriere in Paris and wrote on war neurology. In
      cooperation with Marie, she published a number of articles on postencephalitic
      syndromes, which also became the subject of her 1922 thesis. Three years later,
      she became associate physician at the Paul-Brousse Hospital in Paris, where the
      study of brain tumors became one of the subjects of her scientific work.
      Remarkably, Levy was first author in a few of her many articles, although Roussy
      confirmed that she often initiated the study and even wrote the main part. In
      this article her career is considered in the context of the struggle of women
      physicians to improve their position during the early-twentieth century. She
      probably died from a brain tumor or a postencephalitic syndrome.

PMID- 29469680
TI  - Cognitive Impairment and Social Security's Representative Payee Program.
AB  - Social Security's Representative Payee Program faces a difficult balance with
      respect to dementia: Many people living with dementia can conduct their finances
      without a payee if they have help from informal caregivers, but those without
      help are at risk. To date, it has been unclear what share of retirees with
      dementia use a payee, what share has help potentially available from another
      source, and what share has no observed means of assistance. This study finds that
      while fewer than 10% of retirees with dementia use a payee, only about 8% have no
      observed means of help.

PMID- 29469681
TI  - Lack of Association Between Type 2 Diabetes and the 3673G / A and 9041G / A Gene
      Variants of Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1).
AB  - The vitamin K epoxide reductase complex subunit 1 (VKORC1) gene is expressed in
      many tissue types, and encodes the VKORC1 protein, which is a key enzyme in the
      vitamin K cycle. Although researchers have focused on the effects of vitamin K on
      glucose metabolism, and on its role in the development of type 2 diabetes (T2DM),
      no consensus has yet been reached. Therefore, here we aimed to investigate the
      association between VKORC1 variants and the risk of T2DM. The 3673G / A
      (rs9923231) and 9041G / A (rs7294) VKORC1 variants were investigated by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in
      100 control individuals and 100 patients with T2DM. The genomic regions were
      amplified by PCR; amplicons were digested using the AciI and NciI enzymes and
      visualized by agarose gel electrophoresis. The genotype frequencies of the 3673G
      / A variants were GG (22%), GA (56%), and AA (22%) in the control group and GG
      (19%), GA (52%), and AA (29%) in patients with T2DM (p > 0.05). The genotype
      frequencies of the 9041G / A variants were GG (37%), GA (53%), and AA (10%) in
      the control group and GG (46%), GA (45%), and AA (9%) in patients with T2DM (p >
      0.05). In conclusion, we found no significant correlation between the control
      group and patients with T2DM, with regard to the different genetic models of the
      3673G / A and 9041G / A variants. These data suggest that these VKORC1 gene
      variants may not be linked to T2DM.

PMID- 29469682
TI  - Vitamin D Supplementation in Adults with Vitamin D Deficiency and Its Effect on
      Metabolic Syndrome - A Randomized Controlled Study.
AB  - BACKGROUND: Inverse relationship between metabolic syndrome (MetS) and 25
      hydroxyvitamin D (25(OH) D) levels is controversial. Hypovitaminosis-D has long
      been suspected as a risk factor for glucose intolerance. AIM: A randomized double
      blind placebo controlled study to evaluate effects of vitamin D supplementation
      on insulin resistance in subjects with hypovitaminosis-D and MetS. MATERIALS AND
      METHODS: Subjects were randomized to receive either oral 25(OH) D3 supplement
      (60000 (IU) per week for 8 weeks followed by 60,000 IU monthly for 4 months) or a
      placebo for six months. The parameters measured were blood pressure, vitamin D,
      fasting blood sugar (FBS), insulin, homeostasis model assessment (HOMA),
      quantitative insulin sensitivity check index (QUICKI), body mass index (BMI), and
      waist circumference (WC). RESULTS: There were no significant changes in
      parameters of vitamin-D group compared to placebo group except serum vitamin-D
      was significantly increased in vitamin-D group (p < 0.0001). In vitamin-D group,
      mean WC at baseline was 95.9 +/- 6.66, which significantly changed to 94.6 +/-
      7.47 (p = 0.001). Mean BMI at baseline was 29.1 +/- 4.06 which significantly
      changed to 28.5 +/- 4.16 (p = 0.001). The mean vitamin-D concentration at
      baseline was 15.4 +/- 9.03 which significantly (p < .0001) increased to 26.1 +/-
      11.8. In placebo group mean insulin levels was 10.7 +/- 4.81IU / L which
      increased significantly (p = 0.03) to 15.4 +/- 14.0. Mean QUICKI at baseline was
      0.34 +/- 0.03 which decreased significantly (p = 0.02) to 0.32 +/- 0.03.
      CONCLUSION: In this study the relationship between vitamin D supplementation and
      MetS or IR was not established. Whether achieving vitamin D sufficiency in large
      population-based trials with a longer duration would produce more favorable
      results needs to be assessed.

PMID- 29469683
TI  - Positive Association Between Serum 25-Hydroxy-Vitamin D and Liver Enzymes Levels
      in Healthy Individuals: A Population-Based Study from Iran.
AB  - OBJECTIVE: The relationship between serum 25-hydroxy-vitamin D and within normal
      range liver enzymes in a population-based study in the northwest of Iran was
      investigated. METHOD: This cross-sectional study was comprised of 700 apparently
      healthy Iranian adults (287 men & 413 women) who participated in the major
      lifestyle promotion project (LPP) conducted in East Azarbaijan-Iran in 2015. The
      ultraviolet method and chemiluminescent immunoassay technology were respectively
      used for determination of the serum levels of liver enzymes (alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST)) and 25-hydroxy
      vitamin D. The one-way ANOVA and the linear regression analysis were used for
      statistical analysis. RESULTS: There were not significant differences in mean ALT
      and AST levels regarding different serum 25-hydroxy- vitamin D status. In the
      unadjusted model, serum 25-hydroxy-vitamin D was significantly associated with
      ALT (p = 0.008). The participants in the fourth quartile of 25-hydroxy-vitamin D
      had significantly higher level of ALT compared with participants in the first
      quartile (p = 0.002). After adjustment for age, sex, BMI, waist circumference,
      fasting blood glucose, lipid profile, and dietary vitamin D, this association
      remained significant. For AST, in the unadjusted model, the association between
      serum 25-hydroxy-vitamin D and AST was marginally significant (p = 0.08). The
      participants in the third quartile of 25-hydroxy-vitamin D had significantly
      higher levels of AST compared with participants in the first quartile (p = 0.01).
      CONCLUSION: According to results, there was a positive association between 25
      hydroxy-vitamin D and ALT in individuals without liver diseases. Additional
      prospective studies were needed to confirm this observation and also elucidate
      the underlying mechanisms.

PMID- 29469684
TI  - Editorial; Impact of Drug Metabolism and its Relevance upon Drug Discovery.

PMID- 29469685
TI  - Preface.

PMID- 29469686
TI  - Editorial: The Potential Medicinal Uses of Cassia tora Linn Leaf and Seed
      Extracts.

PMID- 29469687
TI  - Diverse papillomaviruses identified in Weddell seals.
AB  - Papillomaviridae is a diverse family of circular, double-stranded DNA (dsDNA)
      viruses that infect a broad range of mammalian, avian and fish hosts. While
      papillomaviruses have been characterized most extensively in humans, the study of
      non-human papillomaviruses has contributed greatly to our understanding of their
      pathogenicity and evolution. Using high-throughput sequencing approaches, we
      identified 7 novel papillomaviruses from vaginal swabs collected from 81 adult
      female Weddell seals (Leptonychotes weddellii) in the Ross Sea of Antarctica
      between 2014-2017. These seven papillomavirus genomes were amplified from seven
      individual seals, and six of the seven genomes represented novel species with
      distinct evolutionary lineages. This highlights the diversity of papillomaviruses
      among the relatively small number of Weddell seal samples tested. Viruses
      associated with large vertebrates are poorly studied in Antarctica, and this
      study adds information about papillomaviruses associated with Weddell seals and
      contributes to our understanding of the evolutionary history of papillomaviruses.

PMID- 29469688
TI  - Bizionia berychis sp. nov., isolated from intestinal tract of a splendid
      alfonsino (Beryx splendens).
AB  - A Gram-stain-negative, non-motile, aerobic and rod-shaped bacterial strain,
      designated RA3-3-1T, was isolated from splendid alfonsino (Beryxsplendens)
      collected from the North Pacific Ocean. Strain RA3-3-1T grew optimally at 25 
      degrees C, at pH 7.0-8.0 and in the presence of 1.0-3.0 % (w/v) NaCl. The
      neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed
      that strain RA3-3-1T belonged to the genus Bizionia, clustering with the type
      strain of Bizionia fulviae. Strain RA3-3-1T exhibited 16S rRNA gene sequence
      similarities of 98.7, 97.6 and 97.3 % to the type strains of B. fulviae, Bizionia
      paragorgiae and Bizionia saleffrena, respectively, and of 95.5-96.4 % to the type
      strains of the other Bizionia species. Strain RA3-3-1T contained MK-6 as the
      predominant menaquinone and anteiso-C15 : 0, iso-C16 : 0 3-OH, summed feature 3
      (C16 : 1omega7c and/or C16 : 1omega6c), iso-C17 : 0 3-OH, iso-C15 : 0 and C17 : 0
      2-OH as the major fatty acids. The major polar lipids detected in strain RA3-3-1T
      were phosphatidylethanolamine, one unidentified lipid and one unidentified
      aminolipid. The DNA G+C content of strain RA3-3-1T was 34.1 mol% and its DNA-DNA
      relatedness values with the type strains of B. fulviae, B. paragorgiae and B.
      saleffrena were 12-29 %. Differential phenotypic properties, together with its
      phylogenetic and genetic distinctiveness, revealed that strain RA3-3-1T is
      separate from recognized species of the genus Bizionia. On the basis of the data
      presented, strain RA3-3-1T is considered to represent a novel species of the
      genus Bizionia, for which the name Bizionia berychis sp. nov. is proposed. The
      type strain is RA3-3-1T (=KCTC 62140T=NBRC 113024T).

PMID- 29469689
TI  - Genomic and structural features of the yellow fever virus from the 2016-2017
      Brazilian outbreak.
AB  - Southeastern Brazil has been suffering a rapid expansion of a severe sylvatic
      yellow fever virus (YFV) outbreak since late 2016, which has reached one of the
      most populated zones in Brazil and South America, heretofore a yellow fever-free
      zone for more than 70 years. In the current study, we describe the complete
      genome of 12 YFV samples from mosquitoes, humans and non-human primates from the
      Brazilian 2017 epidemic. All of the YFV sequences belong to the modern lineage
      (sub-lineage 1E) of South American genotype I, having been circulating for
      several months prior to the December 2016 detection. Our data confirm that viral
      strains associated with the most severe YF epidemic in South America in the last
      70 years display unique amino acid substitutions that are mainly located in
      highly conserved positions in non-structural proteins. Our data also corroborate
      that YFV has spread southward into Rio de Janeiro state following two main
      sylvatic dispersion routes that converged at the border of the great metropolitan
      area comprising nearly 12 million unvaccinated inhabitants. Our original results
      can help public health authorities to guide the surveillance, prophylaxis and
      control measures required to face such a severe epidemiological problem. Finally,
      it will also inspire other workers to further investigate the epidemiological and
      biological significance of the amino acid polymorphisms detected in the Brazilian
      2017 YFV strains.

PMID- 29469690
TI  - Non-canonical Escherichia coli transcripts lacking a Shine-Dalgarno motif have
      very different translational efficiencies and do not form a coherent group.
AB  - Translation initiation in 50-70 % of transcripts in Escherichia coli requires
      base pairing between the Shine-Dalgarno (SD) motif in the mRNA and the anti-SD
      motif at the 3' end of the 16S rRNA. However, 30-50 % of E. coli transcripts are
      non-canonical and are not preceded by an SD motif. The 5' ends of 44 E. coli
      transcripts were determined, all of which contained a 5'-UTR (no leaderless
      transcripts), but only a minority contained an SD motif. The 5'-UTR lengths were
      compared with those listed in RegulonDB and reported in previous publications,
      and the identities and differences were obtained in all possible combinations. We
      aimed to quantify the translational efficiencies of non-canonical 5'-UTRs using
      GusA reporter gene assays and Northern blot analyses. Ten non-canonical 5'-UTRs
      and two control 5'-UTRs with an SD motif were cloned upstream of the gusA gene.
      The translational efficiencies were quantified under five different conditions
      (different growth rates via two different temperatures and two different carbon
      sources, and heat shock). The translational efficiencies of the non-canonical 5'
      UTRs varied widely, from 5 to 384 % of the positive control. In addition, the non
      canonical transcripts did not exhibit a common regulatory pattern with changing
      environmental parameters. No correlation could be observed between the
      translational efficiencies of the non-canonical 5'-UTRs and their lengths,
      sequences, GC content, or predicted secondary structures. The introduction of an
      SD motif enhanced the translational efficiency of a poorly translated non
      canonical transcript, while the efficiency of a well-translated non-canonical
      transcript remained unchanged. Taken together, the mechanisms of translation
      initiation at non-canonical transcripts in E. coli still need to be elucidated.

PMID- 29469691
TI  - Paracoccus alimentarius sp. nov., isolated from a Korean foodstuff, salted
      pollack.
AB  - A Gram-stain-negative, aerobic, non-motile and coccoid or ovoid bacterial strain,
      designated LB2T, was isolated from a Korean foodstuff, salted pollack. Strain
      LB2T grew optimally at 25-30  degrees C, at pH 7.0-8.0 and in the presence of 0
      2.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences showed that
      strain LB2T belonged to the genus Paracoccus, coherently clustering with the type
      strain of Paracoccus sulfuroxidans. Strain LB2T exhibited 16S rRNA gene sequence
      similarity values of 98.0 and 97.0 % to the type strains of P. sulfuroxidans and
      Paracoccus halophilus, respectively, and of less than 96.9 % to the type strains
      of other Paracoccus species. Strain LB2T contained Q-10 as the predominant
      ubiquinone. Major fatty acids of strain LB2T were cyclo C19 : 0omega8c, C18 :
      1omega7c and C16 : 0 (when grown on MA) or C18 : 1omega7c and C16 : 0 (on TSA).
      The major polar lipids detected in strain LB2T were phosphatidylcholine,
      phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminolipid and one
      unidentified glycolipid. The DNA G+C content of strain LB2T was 61.4 mol% and its
      DNA-DNA relatedness values with the type strains of P. sulfuroxidans and P.
      halophilus were 26 and 18 %, respectively. Differential phenotypic properties,
      together with its phylogenetic and genetic distinctiveness, revealed that strain
      LB2T is separated from recognized Paracoccus species. On the basis of the data
      presented, strain LB2T is considered to represent a novel species of the genus
      Paracoccus, for which the name Paracoccus alimentarius sp. nov. is proposed. The
      type strain is LB2T (=KCTC 62138T=NBRC 113023T).

PMID- 29469692
TI  - The role of interleukin-17 in the pathogenesis of hidradenitis suppurativa.
AB  - Hidradenitis suppurativa is a chronic inflammatory skin condition affecting
      primarily the axillary, perianal, and inguinal areas. Patients with hidradenitis
      suppurativa present with occlusion and subsequent rupture of follicular ducts,
      profound abscesses, fistulae, odorous discharge, fibrosis, and scar formation,
      causing significant morbidity. Knowledge of the pathogenesis of hidradenitis
      suppurativa is limited and treatment with antimicrobial drugs,
      immunosuppressants, and surgical procedures have shown varying results. The
      pathogenic role of the interleukin-17 cytokine family in chronic inflammatory
      skin conditions has been described. Interleukin-17A and interleukin-17F have
      similar properties and induce the production of cytokines, chemokines,
      antimicrobial peptides, and metalloproteinases, all of which take part in the
      inflammatory response. The efficacy of anti-interleukin-17A therapy in psoriasis
      has also been proven and anti- interleukin-17A drugs are already in use for this
      condition. There is currently no consensus on the role of interleukin-17 in the
      pathogenesis of hidradenitis suppurativa. Studies have demonstrated increased
      interleukin-17 mRNA expression in lesional hidradenitis suppurativa skin, whereas
      the protein concentrations of interleukin-17 were found to be normal compared to
      healthy control skin in one other study. A phase II clinical trial on anti-
      interleukin-17 therapy in hidradenitis suppurativa is ongoing.

PMID- 29469693
TI  - Dermatology on Reddit: elucidating trends in dermatologic communications on the
      world wide web.
AB  - Platforms of social media, including the website Reddit, have become increasingly
      popular sites for users to communicate medical information. A study investigating
      dermatology content on Reddit has not been performed in the current literature.
      The purpose of this study is to enumerate the dermatology subreddits, quantify
      subscribers, and characterize posts to estimate the presence of dermatology
      related content on Reddit. A Reddit search of the fourteen most common skin
      diseases globally was performed. Additionally, the terms "dermatology", and
      "skin" were searched in order to identify more subreddits relevant to the field.
      Dermatology-related subreddits that had >=1000 subscribers were evaluated for
      content and categorized for analysis. We identified 38 subreddits related to
      dermatology with subscriber numbers ranging from 52 to 209,973. For 17 of the 38
      subreddits that were further analyzed, most posts fell under the category of
      "seeking health/cosmetic advice." Reddit serves as a communication stage for
      individuals to discuss, engage, and connect on dermatologic topics. Furthermore,
      the platform offers an opportunity for medical professionals to distribute
      evidence-based information concerning dermatologic conditions.

PMID- 29469694
TI  - Dermatology on Snapchat.
AB  - Launched in 2011, Snapchat is one of the newest social media platforms with over
      158 million active daily users. This study investigated the presence of
      dermatology-related content on Snapchat. We searched for Snapchat accounts for
      the top ten most popular dermatology journals, professional dermatological
      organizations, and dermatology-related patient advocate groups on social media.
      None of the above-mentioned entities were found on Snapchat. Plastic surgeons
      were found to primarily utilize the application, although one prominent
      dermatologist was also found. It was theorized that the brevity of the "snaps"
      was a contributing factor for dermatological organizations to not use the
      application. However, Snapchat in the right practice setting may be useful for
      dermatologists, not only to educate followers, but also as a marketing tool to
      Millennials.

PMID- 29469695
TI  - Cutaneous Balamuthia mandrillaris infection as a precursor to Balamuthia amoebic
      encephalitis (BAE) in a healthy 84-year-old Californian.
AB  - Soil and freshwater-dwelling amoebae may opportunistically infect the skin and
      evoke a granulomatous dermatitis that camouflages their underlying morphology.
      Amoebic infestations are incredibly rare in the U.S., predominantly occurring in
      the young, elderly, and immunocompromised. Sadly, because diagnosis is difficult
      and unsuspected, most cases are diagnosed at autopsy. The following case is of a
      healthy 84-year-old man with a non-healing nodulo-ulcerative cutaneous lesion on
      his left forearm that appeared following a gardening injury. Lesional punch
      biopsies repeatedly showed non-specific granulomatous inflammation with no
      pathogens evident histologically or by culture. Histopathologic diagnosis was
      made five months after initial presentation via identification of amoebic
      trophozoite forms in tissue from a large excisional specimen. Anti-amoebic
      therapy was initiated immediately. The patient experienced mental status changes
      three days following lesion excision, with evidence of a cystic mass in the left
      medial parieto-occipital lobe by CT. Both intraoperative brain biopsies and
      cutaneous tissue samples tested positive for Balamuthia mandrillaris by indirect
      immunofluorescent antibody assay performed at the Centers for Disease Control.
      The patient achieved a full recovery on a triple antibiotic regimen. Clinical
      suspicion and thorough histopathologic analysis may determine the difference
      between survival and death for a patient presenting with a treatment-refractory
      localized granulomatous lesion.

PMID- 29469696
TI  - Adalimumab-related alopecia in a patient affected by psoriasis.
AB  - Alopecia induced by biological therapy is a rare side effect of this type of
      drugs. A total of 23 patients of psoriasiform eruptions with severe scalp
      involvement that induced alopecia during anti-tumor necrosis factor (anti-TNF)
      treatment of non-dermatological conditions have been previously reported. We
      present a 50-year-old man affected by plaque psoriasis that developed
      psoriasiform patches with alopecia over his scalp 10 months after initiating
      treatment with adalimumab. Punch biopsy of the alopecic area on the scalp
      revealed psoriasiform epidermal changes and alopecia areata-like dermal changes.
      Along with these findings, there was a dermal inflammatory infiltrate made up of
      eosinophils and plasma cells. In conclusion, scalp psoriasiform lesions with
      alopecia in patients treated with anti-TNF agents have been rarely reported. We
      describe a patient with anti-TNF therapy-related alopecia affected by psoriasis.
      Our patient has a peculiar histology with features of psoriasis and alopecia
      areata in addition to eosinophils and plasma cells. This entity may respond to
      topical treatment. However in patients of severe scalp involvement anti-TNF
      suspension should be considered.

PMID- 29469697
TI  - Generalized bullous fixed drug eruption imitating toxic epidermal necrolysis: a
      case report and literature review.
AB  - Fixed drug eruption (FDE) is defined as sharply demarcated erythematous patches
      or plaques that occur secondary to systemic exposure to a causative medication.
      Eruptions are deemed "fixed" because upon repeated exposure they recur at
      previously affected sites. Generalized bullous fixed drug eruption (GBFDE) is a
      rare FDE variant occurring in patients with a previous history of FDE. Given the
      extensive cutaneous involvement and the frequent mucosal ulcerations associated
      with GBFDE, it is challenging to discern these lesions from Steven-Johnson
      syndrome (SJS) and toxic epidermal necrolysis (TEN). The presence of
      significantly elevated lesional and serum granulysin in SJS/TEN is an important
      discriminating factor because granulysin levels remain significantly lower in
      GBFDE. The implementation of an immunochromatographic test for rapid detection of
      elevated granulysin levels could therefore facilitate the early diagnosis of
      SJS/TEN. We report a case of GBFDE to elucidate the characteristic differences in
      clinical presentation, histopathology, and immunohistochemistry that can
      facilitate diagnosis.

PMID- 29469698
TI  - Acquired bullous acrodermatitis enteropathica as a histologic mimic of pemphigus
      foliaceus in a patient on parenteral nutrition.
AB  - Acquired zinc deficiency can develop as a consequence of poor nutritional intake
      or from dependence on total parenteral nutrition. Acquired zinc deficiency
      dermatitis classically manifests with erosions and scaly plaques in a
      periorificial and acral distribution. We present a case of a woman on parenteral
      nutrition who presented with bullous acrodermatitis mimicking pemphigus foliaceus
      histopathologically. This case highlights clinical and histopathologic variants
      of zinc deficiency that may lead to a delay in diagnosis.

PMID- 29469699
TI  - Mycophenolate mofetil as a successful therapy for idiopathic granulomatous
      mastitis.
AB  - Idiopathic granulomatous mastitis (IGM) is a benign chronic inflammatory breast
      disease of unknown etiology. No consensus exists as to the best therapeutic
      approach, though treatment choices include antibiotics, drainage, surgical
      excision, steroids, methotrexate, and observation. Herein we report a case of
      idiopathic granulomatous mastitis that was refractory to methotrexate and
      intralesional and systemic steroids but responded well to mycophenolate mofetil
      1500mg twice daily. To our knowledge, this is the first report of the effective
      use of mycophenolate mofetil in idiopathic granulomatous mastitis.

PMID- 29469700
TI  - Crystalline folliculitis revealed by non-aqueous staining technique.
AB  - Necrotizing infundibular crystalline folliculitis (NICF) is a rare superficial
      folliculitis characterized by expansive deposits of birefringent crystallized
      lipid. We report a case of NICF in a transplant patient presenting with
      folliculocentric acneiform papules across the lateral face and neck. Biopsy
      demonstrated intrafollicular crystalline deposits within an intact epidermis.
      Diagnostic crystals were identified using a non-aqueous histologic technique
      involving thick unstained sections. To our knowledge, this is the first report of
      NICF in a transplant patient. Our case suggests NICF is a follicular disorder and
      highlights a technique that may prevent loss of birefringent crystals and assist
      in facilitating accurate diagnosis.

PMID- 29469701
TI  - Disseminated cutaneous sporotrichosis presenting as a necrotic facial mass: Case
      and review.
AB  - Sporotrichosis is a subcutaneous mycotic infection caused by Sporothrix
      schenckii, a group of common saprophytes of soil, plants, and organic debris.
      Disseminated forms may be seen in the setting of immunosuppression and are
      typically treated initially with intravenous lipidized amphotericin B. We report
      an unusual case of a 65-year-old woman who developed disseminated cutaneous
      sporotrichosis with extensive facial involvement in the absence of a known
      primary inoculation. Her cutaneous lesions completely resolved after treatment
      with intravenous posaconazole without amphotericin B.

PMID- 29469702
TI  - Infantile bullous pemphigoid with "string of pearls sign".
AB  - Bullous pemphigoid (BP) is an immune mediated bullous disease that is manifested
      by urticarial plaques with superimposed subepidermal blisters and significant
      pruritus. It is generally found in the elderly, but is rare in the pediatric
      population. A 5-month-old girl previously diagnosed with hand-foot-mouth disease
      was examined in our dermatology department owing to vesicles and bullae,
      initially located to the hands and feet, which progressed with new lesions. Tense
      vesicles and bullae distributed in an annular string of pearls pattern on the
      abdomen and facial and cervical regions were noted. Histologic and immunologic
      findings were consistent with the diagnosis of infantile BP. Disease control was
      obtained with oral prednisolone and dapsone; the patient was still in clinical
      remission 6 months after treatment cessation. The differential diagnosis of the
      clinical presentation of the lesions in our patient is of note, given that this
      blistering pattern is frequently reported in association with linear IgA bullous
      dermatosis.

PMID- 29469703
TI  - A pediatric case of unusual melanocytic proliferation of the nail.
AB  - Pigmentation of the nail plate, or melanonychia, is typically a benign condition
      caused by melanocyte activation. Although rare, melanonychia may be the initial
      presentation of melanoma, thus all cases require an in-depth examination.
      Evaluation in pediatric patients can prove especially difficult as benign cases
      have a higher prevalence of atypia compared to adults. Lack of specific treatment
      guidelines in the pediatric population can make diagnosis and treatment
      challenging. We report a pediatric patient with melanonychia with atypical
      features that required significant evaluations and collaboration to ultimately
      reach a treatment plan.

PMID- 29469704
TI  - Congenital juvenile xanthogranuloma with ulceration: a pediatric case report.
AB  - Congenital juvenile xanthogranuloma (JXG) is an uncommon diagnosis and even more
      rarely presents with ulceration. We report such a case in a two-week-old girl.
      Biopsy was performed to rule out any concerning entities. Adequate treatment was
      provided with topical petrolatum and occasional miconozole or zinc oxide; the
      mass spontaneously regressed. Because congenital JXG has an excellent prognosis,
      insight into unique presentations such as this may provide useful information and
      avoid unnecessary surgical interventions.

PMID- 29469705
TI  - Herpes zoster ophthalmicus with associated vasculopathy causing stroke.
AB  - Varicella zoster virus (VZV) is an exclusively human, double-stranded DNA virus.
      Primary infection causes varicella (chickenpox); later the virus becomes dormant
      in the dorsal root, cranial nerve, and autonomic ganglia along the entire span of
      the nervous system, retaining the capacity to reactivate and cause a variety of
      dermal and neurological complications. Recently there has been increasing
      recognition, both clinically and epidemiologically, of the relationship between
      VZV and subsequent strokes. Herein, we describe a case of a previously healthy
      individual with reactivation of VZV causing herpes zoster opthtalmicus along with
      devastating multifocal vasculopathy. It is crucial for dermatologists to
      recognize the dermatomal vesicular eruption in this high risk area to aid in
      prompt diagnosis in an effort to improve clinical prognosis.

PMID- 29469706
TI  - Alopecia universalis unresponsive to treatment with tofacinitib: report of a case
      with a brief review of the literature.
AB  - Janus kinase inhibitors are emerging treatment alternatives in various immune
      mediated diseases including alopecia universalis. Herein, we report a patient
      with psoriasis and alopecia universalis in whom treatment with tofacitinib led to
      remission of psoriasis without improvement in alopecia universalis. Despite the
      promising potential in alopecia areata treatment, research evaluating the
      efficacy of different Janus kinase inhibitors and possible prognostic factors
      related with a more favorable response are warranted.

PMID- 29469707
TI  - Retronychia: an underdiagnosed disease.
AB  - Retronychia is a recently described cause of ingrowth of the nail plate on the
      ventral surface of the proximal nail fold. Clinical features are repeated
      episodes of proximal paronychia, nail plate thickening, and occasionally
      granulation tissue emergence. The usual treatments for paronychia such as
      antibiotics and antifungals are ineffective in these cases. Avulsion of the nail
      plate is the treatment of choice for these patients, but effective treatment is
      usually delayed owing to inadequate diagnosis. Herein, we describe a 28-year-old
      woman with a case of retronychia. She was treated for two months with oral and
      topical antifungal and antibiotics by her general practitioner. After proper
      diagnosis and avulsion of the nail she presented a normal and non-painful growth
      of the affected nail.

PMID- 29469708
TI  - Annular elastolytic giant cell granuloma: a "visible" diagnosis.
AB  - Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous skin
      disease of undetermined cause, characterized by annular plaques with raised
      erythematous borders in sun-exposed skin. The typical histologic features are
      dermal infiltration by multinucleated giant cells, elastin degeneration, and
      elastophagocytosis. The authors describe a clinical case of AEGCG, which
      exhibited an excellent response to hydroxycloroquine.

PMID- 29469709
TI  - Ustekinumab to target granulomatous dermatitis in recalcitrant ulcerative
      necrobiosis lipoidica: case report and proposed mechanism.
AB  - We present a 42-year-old woman with no history of diabetes or glucose intolerance
      who had a 5-year history of ulcerative necrobiosis lipoidica (NL). Despite
      failure of multiple medications, she experienced clearing of her ulcers after her
      treatment was changed to ustekinumab. We discuss our patient's disease course and
      elaborate upon mechanistic reasons for her improvement related to ustekinumab
      therapy.

PMID- 29469710
TI  - Congenital isolated leukonychia.
AB  - Congenital leukonychia is a rare nail disorder that may occur in isolation or in
      association with a number of syndromic disorders. In the following letter, we
      describe a case of isolated congenital true leukonychia to add to the current
      literature. This case is particularly unique in that it does not appear to be
      inherited in an autosomal dominant fashion, in contrast to the majority of
      reported cases.

PMID- 29469711
TI  - Value of dermoscopy for the diagnosis of monilethrix.
AB  - Monilethrix is a rare genodermatosis characterized by a hair shaft dysplasia
      responsible for hypotrichosis. We report the case of a child with monilethrix
      with no associated cases in the family. Trichoscopy facilitated the diagnosis. A
      2-year-old boy presented with diffuse alopecia and persistent fragile hair for
      several months. Clinical examination revealed alopecia with hairs broken several
      millimeters from the scalp. Trichoscopy revealed zones of dystrophic constriction
      of the hair shaft, separated at regular intervals by elliptical nodes of normal
      thickness, giving a "necklace" appearance. The diagnosis of monilethrix was made
      on the basis of these specific features. The diagnosis of monilethrix was more
      difficult to establish in our patient owing to the absence of any familial cases.

PMID- 29469712
TI  - Future growth of physicians and non-physician providers within the U.S.
      Dermatology workforce.
AB  - Trends in the training, supply, availability, career decisions, and retirement of
      US dermatology physicians are not well delineated. The current study evaluates
      whether growth in the dermatology workforce will keep pace with population
      expansion in the United States. A dermatologist supply model was projected to
      2030 drawing on data from the American Academy of Dermatology, American Medical
      Association, Bureau of Labor Statistics, American Association of Medical
      Colleges, and other associations. The clinically active dermatologist workforce
      in 2015 was 36 per capita (1,000,000); entry following postgraduate training was
      age 30 with career separation at age 65 on average. Added to the provider model
      are physician assistants and nurse practitioners in dermatology practices. A
      linear regression micro simulation model based on age cohorts produced a per
      capita supply of dermatology providers of 61 (+/-3) per 1,000,000 by 2030, up
      from 47 in 2016. The dermatology workforce is growing faster than population
      expansion. Workforce estimates could be affected by changing trends in retirement
      and training of dermatology providers. Investments in training of nurse
      practitioners and physician assistants, in addition to training more doctors, may
      be an effective strategy for increasing access to care in populations with low
      dermatologist density.

PMID- 29469713
TI  - Video-based education about systemic corticosteroids enhances patient knowledge
      more than verbal education: A randomized controlled trial.
AB  - BACKGROUND: Video-based patient education about long-term systemic corticosteroid
      treatment has not been assessed. OBJECTIVE: To compare video-based versus verbal
      education in patient knowledge gained and satisfaction. METHODS: English-speaking
      adults (>=18 years) were recruited from March-August 2013 from medical
      dermatology clinics. Study provider clinics were the unit of randomization.
      Verbal subjects heard a script based on the standard discussions of two top
      systemic corticosteroid prescribers at Emory. Video subjects viewed a video
      developed by the investigators. A 12-item survey created by the the investigators
      assessed baseline and post-education knowledge (immediate, one-, three-, and six
      month). RESULTS: Baseline knowledge scores averaged 7.2+/-2.2 correct answers
      with no between-group differences. Post-education, the video group's (N=39) mean
      paired score difference was 0.9+/-2.0 higher than the verbal group's (p<0.04).
      After 1 month, most scores maintained gains with no between-group differences.
      97% of patients in each group were satisfied (none were unsatisfied) with their
      education. LIMITATIONS: Our cohort was more literate than the general public, and
      a minority of subjects completed long-term follow up assessments. CONCLUSION:
      Video education enhanced near-term patient knowledge more than verbal education
      and maintained patient satisfaction.

PMID- 29469714
TI  - Risky business: Behaviors associated with indoor tanning in US high school
      students.
AB  - BACKGROUND: Understanding of associations between indoor tanning and risky health
      related behaviors such as sexual activity and substance abuse among high school
      students across the United States is incomplete. OBJECTIVE: To identify risky
      health related behaviors among high school students utilizing indoor tanning and
      analyze differences between state specific data. METHODS: Results from the Youth
      Risk Behavior Surveillance System (YRBSS) 2013 in 14 different states were
      analyzed. Participants were 90,414 high school students. Responses to questions
      assessing indoor tanning habits, sexual activity, and use of substances were
      analyzed. RESULTS: Sexual activity was associated with indoor tanning in 10 of 14
      states, with Nebraska having the strongest association (adjusted odds ratio, 3.8;
      95% CI, 2.4-6.2; p<0.001). Indoor tanning was also associated with use of
      alcohol, marijuana, ecstasy, cocaine, prescription medications, and cigarettes.
      LIMITATIONS: Only 15 states asked students about their personal history of indoor
      tanning use, and Minnesota was excluded from our analysis as they administered a
      non-YRBS questionnaire. Additionally, our study only analyzed results from the
      2013 YRBS. Lastly, our data was analyzed in 14 individual data sets, giving a
      high likelihood of Type 1 error. CONCLUSIONS: High school students utilizing
      indoor tanning are more likely to engage in sexual activity and substance abuse
      as compared to students who do not utilize indoor tanning.

PMID- 29469715
TI  - Assessment of risk and use of prophylaxis for glucocorticoidinduced-osteoporosis
      among dermatologists in the Pacific Northwest: a survey study.
AB  - OBJECTIVE: Exposure to even physiologic doses of glucocorticoids can reduce one's
      bone mass and increase risk for osteoporotic fracture. There currently exists a
      wide variation in clinician approach to the assessment and management of
      glucocorticoid-induced osteoporosis (GIO). Our objectives were to characterize
      Pacific Northwest dermatology providers' general practices, assessment of risk
      for GIO, and preferred GIO prophylaxis measures by way of survey. To identify
      whether knowledge deficits exist with respect to preventing and managing GIO in
      dermatology patients. DESIGN: A self-administered, 22-question survey was sent
      electronically to respondent population. Surveyed population composed of 392
      dermatology providers of the Washington State Dermatology Association and Oregon
      Dermatology Society registries. Survey responses were collected anonymously via
      Catalyst WebQ. RESULTS: Respondents over-estimated fracture risk and reported
      they would prescribe antiresorptive medications at a less-than-adequate rate.
      When given clinical scenarios and asked to assess risk of major osteoporotic
      fracture, respondents frequently overestimated risk compared to that estimated by
      the FRAX tool (67%-71%). When asked directly if one would prescribe
      bisphosphonates as GIO prophylaxis for a high-risk patient, only 49% responded
      always/almost always. CONCLUSIONS: This study suggests that a knowledge deficit
      exists within dermatology with respect to prevention and screening of GIO. The
      resultant practice gap is likely contributing to morbidity and mortality for
      dermatology patients requiring chronic glucocorticoid use for dermatologic
      disorders. Provider variability in practices suggests that dermatology could
      benefit from additional education in assessment and treatment of GIO, as well as
      a clear set of guidelines for GIO management.

PMID- 29469716
TI  - Associated conditions in patients with multiple dermatofibromas: Case reports and
      literature review.
AB  - Dermatofibromas are benign, fibrohistiocytic, dermal tumors. Solitary
      dermatofibromas may be incidental findings, whereas multiple dermatofibromas may
      be associated with systemic conditions or previous therapies. Two women and one
      man with multiple dermatofibromas and an associated systemic condition,
      immunosuppression, or both, are described. Nine dermatofibromas developed in a
      woman with hypothyroidism, optic neuritis, and Arnold Chiari I malformation. Five
      dermatofibromas developed in a woman with breast cancer who had received several
      systemic antineoplastic therapies. Eleven dermatofibromas developed in a man with
      HIV whose systemic therapies included acyclovir, darunavir/cobicistat,
      dolutegravir, etravirine, and ritonavir. Conditions associated with multiple
      dermatofibromas include autoimmune diseases, cancer, chromosomal abnormalities,
      immunodeficiencies, metabolic disturbances, and altered physiologic states such
      as pregnancy. Medications received by patients with multiple dermatofibromas
      included immunosuppressive agents, psoriasis therapies, and antineoplastic drugs.
      Multiple dermatofibromas can be observed in patients with associated medical
      conditions, systemic therapies, or both. Therefore, in individuals presenting
      with multiple dermatofibromas, not only evaluation for associated disorders, but
      also review of prior and current drug therapies, should be considered.

PMID- 29469717
TI  - Familial pseudoxanthoma elasticum associated with multiple comedones.
AB  - Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized
      by atypical elastic fibers that causes connective tissue abnormalities of the
      skin, eyes, and heart, among other organs. The disorder is rare, with a classic
      presentation of yellow-orange cobblestone-like papules on flexural areas, lax
      skin, ocular degeneration, and moribund vasculature in multiple organs. There is
      wide variability in the presentation of the affected organs [1]. We present two
      sisters with classic cutaneous findings of PXE with the additional unusual
      findings of numerous open comedones on the neck. To our knowledge, this is the
      first report of numerous open comedones in familial PXE.

PMID- 29469718
TI  - Eccrine squamous syringometaplasia in an allogenic stem cell transplant patient
      undergoing chemotherapy.
AB  - Eccrine squamous syringometaplasia (ESS) is a rare finding defined as metaplastic
      change of the cuboidal epithelial cells of eccrine glands into two or more layers
      of squamous epithelial cells. We present a patient who developed ESS after
      induction of CLAG chemotherapy [2-Chlorodeoxyadenosine (2-CdA) with cytarabine
      (Ara-C) and (granulocyte-colony stimulating factor) G-CSF] for management of the
      blast crisis of his chronic myelogenous leukemia (CML). Our patient's ESS
      eruption presented with a variety of morphologies, thus multiple skin biopsies
      were taken to determine the possible diagnosis(es). All skin biopsies showed ESS
      and the eruption resolved with topical corticosteroids after CLAG therapy was
      finished.

PMID- 29469719
TI  - Simultaneous flagellate erythema in a husband and wife secondary to shiitake
      mushroom ingestion.
AB  - Flagellate erythema secondary to shiitake mushroom (Lentinus edodes) ingestion is
      a condition that was first documented in 1977 by Nakamura and has been reported
      in Japan, Europe, and the United States. Herein, we present two cases of
      flagellate erythema after a couple ate a meal containing shiitake mushrooms at a
      chain restaurant. We hypothesize that this condition may not be as rare or as
      dependent on volume of exposure as previously suggested, considering that two
      genetically unrelated individuals simultaneously developed the eruption after
      minimal exposure.

PMID- 29469720
TI  - Erythema multiforme major in a patient with metastatic melanoma treated with
      nivolumab.
AB  - Nivolumab, a relatively novel immune checkpoint inhibitor with FDA approval in
      2014, is gaining greater utilization due to its efficacy in treating metastatic
      melanoma. Many of the cutaneous immune-related adverse events (irAEs) being
      catalogued do not necessitate discontinuation of immunotherapy and are managed
      with supportive therapy. We present a case of erythema multiforme major secondary
      to nivolumab requiring hospitalization and discontinuation of treatment. This is
      only the second reported case of nivolumab-induced erythema multiforme in the
      literature we are aware of, and emphasizes the importance of oncologists working
      in conjunction with dermatologists for prompt diagnosis and management.

PMID- 29469721
TI  - Lupus and scleroderma overlap features in a 28-year-old man with anti-PL-12 anti
      synthetase syndrome.
AB  - A 28-year-old man with clinically and laboratory diagnosed anti-PL-12 anti
      synthetase syndrome (AS) in 2009 developed cutaneous lupus lesions, discoid lupus
      lesions, and sclerodacytly with finger-tip ulcerations four years following his
      AS diagnosis. Laboratory tests including +ANA, +anti-dsDNA antibody, +anti-Smith
      antibody, and +anti-RNP antibody in 2014 confirmed the diagnosis of progression
      to an overlap syndrome including systemic lupus erythematosus. The patient now
      also has clinical findings (sclerodacytly, Raynaud phenomenon, finger-tip
      ulcerations) consistent with scleroderma overlap. In each stage of his evolving
      connective tissue disease, cutaneous findings have been central to the
      recognition and monitoring of his overlap syndromes.

PMID- 29469722
TI  - Acquired elastoma in a subungual location.
AB  - Elastomas are connective tissue nevi or hamartomas. They may occur in isolation
      or can be associated with familial syndromes such as Buschke-Ollendorff syndrome.
      Elastomas typically present in childhood as small ivory papules or firm skin
      colored nodules that can coalesce into larger yellow plaques. These lesions are
      typically distributed over the extremities, abdomen, and back. Herein, we report
      an unusual case of a renal transplant recipient who presented with an acquired
      subungual papule with associated koilonychia and distal nail plate dystrophy.
      Histopathologic findings were consistent with subungual elastoma.

PMID- 29469723
TI  - Mycobacterium haemophilum infection in a renal transplant patient with
      inflammatory bowel disease.
AB  - A 61-year-old immunosuppressed renal transplant patient with inflammatory bowel
      disease presented with tender pink nodules on the trunk and extremities. An
      initial biopsy was suggestive of metastatic Crohn disease, but after disease
      persistence, a second biopsy revealed disseminated Mycobacterium haemophilum.
      Atypical mycobacterial infections should be considered in immunosuppressed
      patients. This case highlights the complexities of diagnosing such infections in
      patients with an underlying granulomatous condition and the particular growth
      requirements of M. haemophilum.

PMID- 29469724
TI  - Oral lesions as an important marker for HIV progression.
AB  - BACKGROUND: Oral hairy leukoplakia (OHL) is a benign lesion caused by Epstein
      Barr virus (EBV) replication in the oral epithelium affecting the borders of the
      tongue. It is strongly associated with immunosuppression, especially in HIV+
      adults but is uncommon in pediatric population. The aim of the study is to show
      the importance of the correct diagnosis of OHL and its influence on HIV
      treatment.We report two cases of HIV+ adolescent patients that presented with
      leukoplakic lesions on the border of the tongue, suggestive of OHL. OHL diagnosis
      was confirmed in only one case through EBV in situ hybridization. After
      confirmation of the diagnosis, the patient with OHL was referred to an infectious
      disease specialist with the decision to start antiretroviral therapy. CONCLUSION:
      OHL definitive diagnosis can help clinical management of pediatric HIV+ patients.

PMID- 29469725
TI  - Histiocytoid autoimmunity-related neutrophilic dermatosis in a patient with
      rheumatoid arthritis.
AB  - Autoimmunity-associated neutrophilic dermatoses are a recently recognized
      manifestation of connective tissue diseases, in particular, lupus erythematosus.
      These entities are clinically and sometimes histopathologically distinct from
      classic neutrophilic dermatoses. We describe a case of an autoimmunity-related
      neutrophilic dermatosis in a patient with rheumatoid arthritis. In addition to
      this uncommon association, there was an absence of mature neutrophils and a
      population of immature histiocytoid granulocytes. This unusual case expands the
      concept of histiocytoid neutrophilic dermatoses to include those seen in
      association with autoimmune connective tissue diseases.

PMID- 29469726
TI  - Psoriasiform mycosis fungoides: a rare form of the disease with review of the
      literature.
AB  - BACKGROUND: Mycosis fungoides (MF) typically presents as erythematous scaly
      patches or plaques that may progress to cutaneous tumors. Although MF may be
      presented like other dermatoses, initial presentation as psoriasiform plaques
      simulating psoriasis is rare. Differentiating MF from psoriasis is important
      because systemic therapies used for psoriasis can worsen MF. We describe a case
      of psoriasiform MF and we also review the clinicopathological features of similar
      cases in the literature. CASE: A 46-year-old woman was referred to our clinic
      with a history of psoriasiform plaques for 13 years. She had multiple,
      generalized, indurated plaques with thick psoriasiform scales that were
      unresponsive to topical treatments. The histopathology showed marked psoriasiform
      epidermal hyperplasia with epidermotropic atypical lymphocytes compatible with
      MF. Immunohistochemical (IHC) staining showed that atypical lymphocytes were
      positive for CD3, CD4, CD8, and CD5. Of note, upper dermal and intraepidermal
      large atypical lymphocytes were CD30 positive. The review of similar psoriasiform
      MF cases revealed that they had all been treated as psoriasis for many years and
      finally diagnosed as MF especially after deterioration induced by
      immunosuppressive therapies. CONCLUSIONS: In presumed cases of psoriasis that are
      unresponsive to treatment, progressive, or ulcerative, biopsy should be
      considered to rule out MF, particularly before starting a potent
      immunosuppressive agent.

PMID- 29469727
TI  - Painful subcutaneous nodules on the thigh.
AB  - Osteoma cutis is the presence of bone within the dermis or subcutaneous tissue.
      This condition may occur sporadically or secondary to other dermatologic or
      genetic conditions. We present a 12-year-old girl with pseudohypoparathyroidism
      type-Ia who developed osteoma cutis on the right thigh.

PMID- 29469728
TI  - Generalized eruptive syringomas.
AB  - Eruptive syringoma is a rare variant of syringoma, benign neoplasms of the
      eccrine sweat ducts that appear on the face, neck, chest, and axillae of
      predominately Asian and African American women before or during puberty [1, 2].
      Lesions appear as small skin-colored or slightly pigmented, flat-topped papules
      [2]. The condition can be cosmetically disfiguring and difficult to treat,
      especially in dark-skinned patients. The investigators report a 52-year old
      Guyanese woman who presented with widespread, chronic, non-pruritic and
      nontender, skin-colored papules that arose approximately 20 years earlier. A
      punch biopsy of affected skin was obtained and the histological diagnosis was
      eruptive syringoma. The patient pursued no further treatment, after discussion of
      costs and risks.

PMID- 29469729
TI  - A pedunculated lesion on the foot: acquired fibrokeratoma.
AB  - Acquired fibrokeratomas are benign and uncommon lesions consisting of collagenous
      papules and nodules covered by hyperkeratotic epidermis. These tumors occur
      mainly on the fingers and toes and infrequently on the palms and soles. They may
      possibly be triggered by a reaction to a trauma and presents as small and
      solitary dome-shaped lesions with a collarete of slightly raised skin at the
      base. Several case reports have been published of this rare lesion, with only a
      few investigators describing lesions of the feet.

PMID- 29469730
TI  - A giant apocrine hidrocystoma of the trunk.
AB  - Hidrocystomas are benign cysts that typically present as translucent, bluish
      dermal nodules on the face and are rarely > 1 cm in size. They are classically
      categorized as eccrine or apocrine based on histologic features. We present a
      rare case of a giant apocrine hidrocystoma of the trunk, demonstrating that,
      although a rare variant, apocrine hidrocystomas can present both off the head and
      neck, and can be significantly larger in size than previously reported.

PMID- 29469731
TI  - Local skin reactions following the administration of topical ingenol mebutate for
      actinic keratosis.
AB  - Actinic keratoses are cutaneous lesions that appear as the result of the
      proliferation of atypical keratinocytes. These lesions are considered pre
      malignant and they can progress to squamous cell carcinoma. Ingenol mebutate has
      been approved as an effective treatment for AK on the face and trunk. We studied
      the local skin reactions to this therapy. Data about local skin reactions were
      collected in a series of 5 patients with photographic documentation, a visual
      analog scale, and a ranking of satisfaction of the patient. Moderate to severe
      reactions were reported in most of patients, but only one stopped treatment
      early. The short duration of treatment contributes to high adherence to the
      therapy.

PMID- 29469732
TI  - Mycobacterium fortuitum infection after acupuncture treatment.
AB  - Actinic keratoses are cutaneous lesions that appear as the result of the
      proliferation of atypical keratinocytes. These lesions are considered pre
      malignant and they can progress to squamous cell carcinoma. Ingenol mebutate has
      been approved as an effective treatment for AK on the face and trunk. We studied
      the local skin reactions to this therapy. Data about local skin reactions were
      collected in a series of 5 patients with photographic documentation, a visual
      analog scale, and a ranking of satisfaction of the patient. Moderate to severe
      reactions were reported in most of patients, but only one stopped treatment
      early. The short duration of treatment contributes to high adherence to the
      therapy.

PMID- 29469733
TI  - Nasolabial flap - alternative uses for a classic but versatile technique.
AB  - The nasolabial flap is one of the most ancient techniques used in orofacial
      surgery. The authors report two cases of patients with skin cancer treated
      surgically with variations of the classic nasolabial flap by transposition
      (bilateral and folded) that highlight the broad applicability of this technique.

PMID- 29469734
TI  - Clinical resolution of pemphigus vulgaris on rituximab.
AB  - Although significant progress has been made for the treatment of pemphigus
      vulgaris (PV) with rituximab (RTX), a consensus remains to be determined for
      standard treatment protocol, regarding optimal dosing, infusion regimen, and use
      of concomitant immunotherapy to achieve safe, effective, and rapid clinical
      response. We describe a patient with pemphigus vulgaris treated with high dose
      rituximab with the rheumatoid arthritis protocol along with intravenous
      immunoglobulin therapy. This case provides evidence towards the growing body of
      research needed to modify and improve treatment for pemphigus using rituximab.

PMID- 29469735
TI  - Quantitative ABCD parameters measured by a multispectral digital skin lesion
      analysis device for evaluation of suspicious pigmented skin lesions strongly
      correlate with clinical ABCD observations.
AB  - : Background/Study Aim: A multispectral digital skin lesion analysis (MSDSLA)
      device has proven to be sensitive and specific for malignant melanoma (MM)
      detection by dermatologists and may have other useful applications. This study
      aimed to develop and test objective quantitative Asymmetry, Border irregularity,
      Color, and Diameter (qABCD) parameters for MSDSLA and correlate them with the
      presence of clinical ABCD features to aid the decision to biopsy a suspicious
      pigmented skin lesions (PSLs). METHODS: 1632 benign and malignant [175 MM/High
      Grade Dysplastic Nevi (HGDN)] were evaluated for their qABCD parameters.
      Quantitative characteristics were correlated with the presence of clinical ABCD
      features identified by independent dermatologists. RESULTS: qA, qB, qC, and qD
      had correlations of 78%, 73%, 76%, and 86%, respectively, for non-MM/HGDN
      lesions. The correlations for qA, qB, qC, and qD for MM/HGDN lesions was 86.3%,
      83%, 89%, and 89%, respectively. All repeatability parameters were statistically
      significant. CONCLUSIONS: This study demonstrates qABCD values are repeatable and
      strongly correlate with the clinical ABCD features. qABCD characteristics provide
      an additional objective and reliable means of identifying PSLs that need further
      evaluation to rule out MM and, in combination with the clinical ABCDs, may allow
      for improved assessment when evaluating the malignant potential of PSLs.

PMID- 29469736
TI  - The impact of ultraviolet radiation on sunburn-related search activity.
AB  - We establish a strong, positive relationship between the Ultraviolet Index and
      Google search engine activity for sunburn-related terms in the United States.
      Using the Google Trends utility and data available from the National Weather
      service, we combine data from a twelve-year period to produce panel data for each
      state. We fit a time-series regression model of search activity and perform
      statistical tests on the resulting parameter estimates. This study lays the
      groundwork for using search-related data to assess the prevalence of, and
      attitudes about sunburn. By tracking the frequency of searches about preventative
      measures like "sunscreen" or "protective clothing" versus treatment measures like
      "sunburn relief," researchers could measure the effectiveness of awareness and
      prevention programs.

PMID- 29469737
TI  - Telangiectasia macularis eruptiva perstans: an old terminology, still frequently
      used.
AB  - The term telangiectasia macularis eruptiva perstans (TMEP) was originally used to
      describe a rare form of cutaneous mastocytosis (CM) that was limited to the skin
      with lesions consisting of irregular, telangiectatic macules ranging in color
      from red to brown. Recent guidelines, however, recommended that the sole presence
      of telangiectasias should not form the basis of a distinct variant of CM. We
      conducted a review of the literature from 1930 to 2017 and found 76 cases that
      were reported as TMEP. Owing to a general misconception about diagnosis of CM and
      SM, there is a need for further discussion and awareness of the newly proposed
      World Health Organization (WHO) guidelines.

PMID- 29469738
TI  - Dermatologic manifestations of acromegaly: A case in point and a focused review.
AB  - Acromegaly is a systemic syndrome caused by overproduction of growth hormone.
      Cutaneous, endocrine, cardiovascular, skeletal, and respiratory systems are
      affected. Cutaneous changes in acromegaly relate to overexpression of growth
      hormone and insulin-like growth factor 1 on skin cells and adnexa. Dermal
      glycosaminoglycan accumulation and edema cause skin distention that is most
      prominent in the face, hands, and feet. Oily skin with large pores,
      hypertrichosis, and excessive sweating are common features. Pigmented skin tags,
      acanthosis nigricans, and psoriasis are also encountered. Cutaneous
      manifestations of acromegaly are various and prominent, and are an important clue
      for the early diagnosis and treatment of this high-morbidity disorder.

PMID- 29469739
TI  - Cowden syndrome: clinical case and a brief review.
AB  - Cowden syndrome is a rare genodermatosis of autosomal dominant inheritance
      characterized by multiple hamartomas in several organs and an increased risk of
      malignancies. We present the case of a 53-year-old man with a history of benign
      and malignant thyroid disease, intestinal polyposis, and Chiari malformation. He
      had several trichilemmomas, papillomatosis of the oral cavity, macular
      pigmentation of the glans penis, among other clinical features suggestive of
      Cowden syndrome. Given the suspicion, genetic study was conducted and PTEN
      mutation was identified. Cowden syndrome affects 1:200,000 individuals.
      Mucocutaneous lesions are almost always present and there may be other typical
      features involving other organs, namely thyroid, colon, and brain. Mucocutaneous
      lesions may be the initial manifestation of this disorder and usually precede the
      onset of malignant lesions, making timely diagnosis essential for proper
      monitoring and screening.

PMID- 29469740
TI  - A toxic epidermal necrolysis-like presentation of linear IgA bullous dermatosis
      treated with dapsone.
AB  - Linear IgA bullous dermatosis is a rare autoimmune vesiculobullous disease
      characterized by linear deposition of IgA along the basement membrane zone. It is
      classically idiopathic, but may also arise secondary to drug exposure. A
      heterogeneous spectrum of clinical features has been described, including a rare,
      morbid variant mimicking toxic epidermal necrolysis. Herein, we present a case of
      vancomycin-induced linear IgA bullous dermatosis that manifested clinically as
      toxic epidermal necrolysis and resolved with dapsone therapy.

PMID- 29469741
TI  - An unusual presentation of primary cutaneous amyloidosis.
AB  - Primary localized cutaneous amyloidosis refers to a group of disorders
      characterized by deposition of amyloid in the dermis without any systemic
      involvement. It comprises the following clinical types: macular, lichenoid,
      nodular, and biphasic. There are also rare variants such as amyloidosis cutis
      dyscromica and poikiloderma-like cutaneous amyloidosis. We report a case of
      primary cutaneous amyloidosis in a 17-year-old boy with unusual pigmentation of
      various patterns (reticulate and diffuse pigmentation with mottling and rippling
      at places) and hypopigmented atrophic macules. Our patient also had nail, oral,
      and mucosal pigmentation that have not been described. Amyloid deposits were
      shown histopathologically in both hyperpigmented and hypopigmented macules.

PMID- 29469742
TI  - Unique urticarial presentation of minocycline-induced lupus erythematosus.
AB  - The association between guttate psoriasis and infection with group A
      Streptococcus (GAS) has been well established in the medical literature. However,
      responses to treatments aimed at GAS eradication such as systemic antibiotics or
      tonsillectomy are inconsistent. Further complicating treatment recommendations
      for a disease with a suspected microbial trigger, the standard therapy for severe
      psoriasis is with systemic immunosuppressant medications. This case report
      illustrates the role of GAS as a trigger for acute onset severe psoriasis in a
      child whose skin disease initially worsened with a trial of methotrexate. An
      immune evaluation confirmed a co-existing selective antibody deficiency.
      Subsequent treatment with intravenous immune globulin dramatically improved his
      underlying immune function and decreased GAS infections. This improvement in
      overall immune function and decrease in GAS infections cleared his skin disease.
      An interval change in formulation to subcutaneous immune globulin was not as
      effective.

PMID- 29469743
TI  - Treatment of selective antibody deficiency with IVIG resulting in decreased
      frequency of streptococcal infection and improvement of guttate psoriasis.
AB  - The association between guttate psoriasis and infection with group A
      Streptococcus (GAS) has been well established in the medical literature. However,
      responses to treatments aimed at GAS eradication such as systemic antibiotics or
      tonsillectomy are inconsistent. Further complicating treatment recommendations
      for a disease with a suspected microbial trigger, the standard therapy for severe
      psoriasis is with systemic immunosuppressant medications. This case report
      illustrates the role of GAS as a trigger for acute onset severe psoriasis in a
      child whose skin disease initially worsened with a trial of methotrexate. An
      immune evaluation confirmed a co-existing selective antibody deficiency.
      Subsequent treatment with intravenous immune globulin dramatically improved his
      underlying immune function and decreased GAS infections. This improvement in
      overall immune function and decrease in GAS infections cleared his skin disease.
      An interval change in formulation to subcutaneous immune globulin was not as
      effective.

PMID- 29469744
TI  - Folliculin mutation-negative trichodiscomas in a patient with multiple endocine
      neoplasia type I syndrome.
AB  - Mycosis fungoides (MF) is the most common cutaneous T cell lymphoma that involves
      the oral mucosal. The manifestation of lesions within the oral cavity generally
      correlates with a poor prognosis. Management of MF includes skin directed
      therapies and localized radiation treatment, with systemic biologic therapies and
      chemotherapy used for more advanced stages. The clinical and histologic features
      of MF in a patient with oral disease are reviewed.

PMID- 29469745
TI  - Oral involvement of cutaneous T-cell lymphoma.
AB  - Methylisothiazolinone (MI) is commonly used as a preservative in personal care
      products and is a frequent cause of allergic contact dermatitis. We present a
      patient with allergic contact dermatitis caused by MI in hair care products and
      discuss this allergen to bring attention to this common cause of contact
      dermatitis, and to highlight its frequent use in hair care products. If allergy
      to MI is suspected, testing should be performed to this individual preservative,
      as testing solely for the combination preservative,
      methylisothiazolinone/methylchloroisothiazolinone (Kathon CG(r)), may miss many
      cases of MI allergy.

PMID- 29469746
TI  - Allergic contact dermatitis to methylisothiazolinone in hair care products:
      report of a case.
AB  - Eccrine spiradenoma (ES) typically presents as a solitary tender lesion. Multiple
      ES is a rare variant of ES and can present in a segmental, linear, blaschkoid, or
      zosteriform pattern. The etiology of multiple ES is unknown, but several theories
      have been suggested including a multipotent stem cell origin. We report the case
      of a 30-year-old woman with multiple painful ES in a zosteriform pattern on the
      mid-back and abdomen. Skin biopsy of a representative lesion demonstrated a
      circumscribed tumor nodule encapsulated by a fibrous capsule with diffuse dense
      basophilic proliferation located in the dermis. The lesions were then excised on
      two separate sessions without recurrence.

PMID- 29469747
TI  - Multiple eccrine spiradenomas in a zosteriform pattern.
AB  - Eccrine spiradenoma (ES) typically presents as a solitary tender lesion. Multiple
      ES is a rare variant of ES and can present in a segmental, linear, blaschkoid, or
      zosteriform pattern. The etiology of multiple ES is unknown, but several theories
      have been suggested including a multipotent stem cell origin. We report the case
      of a 30-year-old woman with multiple painful ES in a zosteriform pattern on the
      mid-back and abdomen. Skin biopsy of a representative lesion demonstrated a
      circumscribed tumor nodule encapsulated by a fibrous capsule with diffuse dense
      basophilic proliferation located in the dermis. The lesions were then excised on
      two separate sessions without recurrence.

PMID- 29469748
TI  - Mycobacterium marinum infection contracted from seaweed wrap in a psoriasis
      patient undergoing treatment with adalimumab.
AB  - We report a patient with psoriasis who developed Mycobacterium marinum (M.
      marinum) infection after seven years of treatment with adalimumab, a human anti
      TNF (tumor necrosis factor) monoclonal antibody. TNF is a pro-inflammatory
      cytokine that plays a central role in the pathogenesis of psoriasis and a number
      of other immune-mediated inflammatory diseases. TNF plays an important role in
      granuloma formation and host defense against mycobacterial infections. Several
      cases of atypical mycobacterial infections in patients on TNF inhibitors have
      been reported. To our knowledge, this is the second reported case of M. marinum
      infection in a patient on adalimumab for the treatment of psoriasis.

PMID- 29469750
TI  - A case of probable trimethoprim-sulfamethoxazole induced circulating
      antineutrophil cytoplasmic antibody-positive small vessel vasculitis.
AB  - Cutaneous leukocytoclastic vasculitis (LCV) can occur as skin-limited disease or
      as part a systemic vasculitis. Appropriate workup includes the evaluation of
      antineutrophil cytoplasmic antibodies (ANCAs), with a positive titer raising
      concern for the associated primary vasculitides including microscopic
      polyangiitis (MPA), granulomatosis with polyangiitis (GPA), or eosinophilic
      granulomatosis with polyangiitis (EGPA). In the absence of systemic findings,
      however, a drug etiology must also be considered. Tumor necrosis factor (TNF)
      inhibitors, propylthiouracil, levamisole-adulterated cocaine, hydralazine, and
      minocycline have been previously documented to induce ANCA-positive vasculitis
      (APV), which may present with conspicuously high ANCA titers. Herein we report
      trimethoprim-sulfamethoxazole as another culprit in drug-induced APV. Our case
      reinforces the need to consider drug etiology for APV and cautions against
      interpreting positive ANCAs as equivalent to evidence of systemic disease.

PMID- 29469749
TI  - Trimethoprim-sulfamethoxazole-induced linear IgA bullous disease presenting as
      toxic epidermal necrolysis.
AB  - BACKGROUND: Linear IgA bullous dermatosis (LABD) is an autoimmune blistering skin
      disorder characterized by linear IgA deposits along the dermoepidermal junction.
      Usually idiopathic, LABD can be drug-induced. OBJECTIVE: To report the atypical
      characteristics of a case of trimethoprim-sulfamethoxazole-induced LABD
      presenting as toxic epidermal necrolysis (TEN). METHODS: A 63-year-old woman
      treated with trimethoprim-sulfamethoxazole for Pneumocystis jirovecii infection
      developed a generalized maculopapular rash with herpetiform lesions, rosette-like
      lesions, and tense bullae with Nikolsky sign. RESULTS: Anti-basement membrane
      zone antibodies were negative, but immunoblot revealed a 160 kDa band
      corresponding to subepidermal class IgA desmoglein 1. Skin biopsy specimens
      revealed a subepidermal bulla and direct immunofluorescence showed linear IgA
      deposition along the basement membrane zone. A diagnosis of toxic epidermal
      necrolysis was excluded and replaced by trimethoprim-sulfamethoxazole-induced
      LABD. CONCLUSION: We report a case of trimethoprim-sulfamethoxazole-induced LABD
      with a 160 kDa IgA desmoglein 1 found by immunoblotting analysis, probably by
      epitope spreading.

PMID- 29469751
TI  - Staphylococcus lugdunensis cutaneous infection with sporotrichoid distribution.
AB  - We report the occurrence of Staphylococcus lugdunensis cutaneous infection with
      sporotrichoid distribution of the left lower limb of a 60-year-old man. Recent
      studies have confirmed that Staphylococcus lugdunensis is a significant pathogen
      in causing skin and soft tissue infections that usually manifest in abscesses,
      surgical wound infections, and cellulitis. It used to be considered a skin
      commensal bacteria, but if unrecognized it can lead to  fulminant endocarditis,
      meningitis, skin abscesses, peritonitis, and spondylodiscitis.

PMID- 29469752
TI  - Cutaneous infection with Mycobacterium fortuitum after subcutaneous injection of
      human chorionic gonadotropin.
AB  - Weight loss clinics are common in the United States.  Unfortunately, some offer
      dubious weight loss methods such as self-administered human chorionic
      gonadotropic (HCG) injections. HCG products are unregulated, yet, widely
      available. Infection is among the risks potentially associated with this
      treatment.  We report a case of skin infection caused by Mycobacterium fortuitum
      after HCG injection.

PMID- 29469753
TI  - A case of de novo palmoplantar psoriasis with psoriatic arthritis and autoimmune
      hypothyroidism after receiving nivolumab therapy.
AB  - Nivolumab, a monoclonal antibody against the programmed cell death protein 1 (PD
      1), has shown promising results in patients with advanced malignancies, including
      melanoma, lung cancer, and renal cancer. Immune-related adverse events (irAEs)
      have been reported, including both organ-specific toxicities and skin toxicities.
      Herein, we report a case of predominantly palmoplantar psoriasis with severe nail
      involvement, psoriatic arthritis, and autoimmune hypothyroidism after receiving
      nivolumab treatment for lung cancer. We also summarize the case reports that have
      been published previously. The knowledge of these irAEs in patients undergoing
      anti-PD1 therapy is important since it will enable earlier recognition and
      appropriate management, with the aim of maintaining effective dose without
      disruption.

PMID- 29469754
TI  - Clinical improvement of a patient with both amyopathic dermatomyositis and
      psoriasis following treatment with cyclosporine.
AB  - Clinically amyopathic dermatomyositis (CADM) is an uncommon subtype of
      dermatomyositis that rarely presents simultaneously with psoriasis. There are
      subsequently few reports discussing the management of concurrent CADM and
      psoriasis. Furthermore, skin lesions of CADM are often recalcitrant to first line
      dermatomyositis interventions. We present a case of a 45-year-old woman with both
      CADM and psoriasis whose lesions were resistant to multiple therapies; she
      eventually achieved disease control and remission with cyclosporine.

PMID- 29469755
TI  - Atypical presentations of pityriasis rosea: a reply.
AB  - Pityriasis rosea (PR) may have atypical presentations as regards morphology and
      distribution of the lesions. Recently, several forms of PR considered atypical
      for the course of the disease have been described. Differently from the typical
      PR that resolves within 2-12 weeks, relapsing and persistent PR forms (lasting
      longer than 12 weeks) have been described in adults and children. Lesions of the
      oral mucosa in PR may be more common than as reported in the literature.
      Formerly, the occurrence of oral lesions in PR has been considered more frequent
      in dark-skinned patients compared to light-skinned patients. However, in 12
      Caucasian adult patients with persistent PR that have been recently described,
      oral lesions were very common (75% of cases). Another study on the clinical
      features and virological parameters of 31 Caucasian children with PR showed that
      painless oropharyngeal lesions were present in 35% of them, a rate much higher
      than those reported in adult dark-skinned (9%) and Caucasian patients (16%) with
      typical PR.

PMID- 29469756
TI  - Essential telangiectasia in an infant: a diagnosis to be considered.
AB  - Essential generalized telangiectasia as the result of postcapillary venule
      dilatation, is characterized by the sudden development of generalized
      telangiectasias, sometimes involving the conjunctiva. A few pediatric cases have
      been reported. The main condition in the differential diagnosis includes
      syndromes with telangiectasia such as hereditary hemorrhagic telangiectasia of
      Rendu-Osler, unilateral nevoid telangiectasia, and neonatal lupus erythematous.
      We present an 11-month-old boy that presented because of telangiectasia located
      on the face and neck. The telangiectasias appeared at two months of age and
      followed a progressive course. Nd-YAG laser therapy could be an interesting
      therapeutic approach in cosmetically compromised cases.

PMID- 29469757
TI  - Delusions of parasitosis: a brief review of the literature and pathway for
      diagnosis and treatment.
AB  - A large proportion of patients seen in dermatology practices have underlying
      psychological issues associated with their skin diseases. One of the most
      flagrant examples of this are patients with delusions of parasitosis. These
      patients have false fixed beliefs that they are infested by parasites and
      experience cutaneous sensations of crawling, biting, and stinging associated with
      their delusions. There is no organic skin disorder and all cutaneous
      manifestations are self-induced. Rather than a psychiatrist, the dermatologist is
      often designated by the patient to handle the chief complaint, even though the
      main disorder is psychogenic. In spite of their limited evidence, antipsychotic
      medications have become the mainstay of therapy for delusions of parasitosis. The
      dermatologist must therefore be familiar with the approach to diagnosis and the
      use of antipsychotic or neuroleptic medications, which usually reside in the
      domain. There are few clinical trials and no substantial randomized controlled
      trials examining the efficacy of the psychiatrist antipsychotic medication used
      to treat delusions of parasitosis. This review article synthesizes the current
      available research and distils it down to analyzes 17 case reports, comprising 37
      cases, examining the use of risperidone and olanzapine in the treatment of
      delusions of parasitosis. These findings are synthesized into a clinical pathway
      designed to assist dermatologists in effectively managing patients with delusions
      of parasitosis.

PMID- 29469758
TI  - A pilot program for community dermatologists working with primary care residents
      to provide dermatology consults to a regional hospital.
AB  - With the high demand and limited supply of dermatologists, the majority dedicate
      their time primarily to outpatient practice. A number ofobstacles to inpatient
      dermatology consults have been described, as well as the essential benefits for
      some of the sickest patients. Dermatology residency programs partially relieve
      this need, however with the transition to a single Graduate Medical Education
      accreditation system and many previously American Osteopathic Association
      accredited dermatologyprograms ceasing to train residents after 2020, it is
      prudent to recruit additional possible consultants. One possible solution is to
      involve non-dermatology residents as part of the consult service team. We report
      on our experience of piloting such a program, for community dermatologists
      providing consults to a regional hospital utilizing family medicine andinternal
      medicine residents.

PMID- 29469759
TI  - Vaccine-induced toxic epidermal necrolysis: A case and systematic review.
AB  - BACKGROUND: Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic
      epidermal necrolysis (TEN) are cutaneous hypersensitivityreactions that develop
      in response to specific triggers such as medications and certain infections.
      Vaccines, which undergo rigorous safety testing prior to use in humans, are a
      rare cause of SJS/TEN and little is known about the frequency of such events and
      corresponding pathogenesis. OBJECTIVE: Herein, we discuss a case of suspected TEN
      in a 19-year-old woman who received the meningococcal B vaccine (the first report
      of such an association) and conduct a systematic review of the associated
      literature. We also discuss management of this patient with a single dose of
      etanercept. METHODS: Relevant literature was searched using the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method.
      RESULTS: A total of 29 articles reporting EM, SJS, or TEN following vaccination
      were included from >5 countries. Of the 29, 22 articles reported EM, 6/29
      reported SJS, and 4/29 reported TEN (3 articlesreported cases of both EM and
      SJS/TEN). CONCLUSIONS: We suggest consideration of vaccines as an etiology for
      cases of SJS or TEN that begin with an EM-like presentation, and provide further
      evidence for the use of etanercept as a viable treatment for TEN.

PMID- 29469760
TI  - The use of cyclosporine for Stevens-Johnson syndrome-toxic epidermal necrolysis
      spectrum at the University of Louisville: A case series and literature review.
AB  - INTRODUCTION: Cyclosporine therapy for Stevens-Johnson syndrome-toxic epidermal
      necrolysis (SJSTEN) was first reported in the literature by Renfro et al. in
      1989. Herein we report an additional 4 cases of SJS-TEN treated with
      cyclosporine. METHODS: Case information was collected retroactively at the
      University of Louisville Hospital in Louisville, KY. All cases had a diagnosis of
      SJS or TEN by a dermatologist. All patients were >=18 years of age and treated
      with cyclosporine during their admission. RESULTS: Three of four patients re
      epithelialized within an average of 3.67 days of starting 3-4 mg/kg/day of
      cyclosporine. One patient passed away, likely due to advanced endometrial cancer.
      DISCUSSION: We provide a review of the literature on cyclosporine use for
      SJS/TEN, including various outcome measures - stabilization (cessation of new
      lesions), time to re-epithelialization, mortality rate, and hospital length of
      stay and, where available, comparison to other systemic agents. CONCLUSION: The
      outcomes appear to be consistent with rapid re-epithelialization and low
      mortality as seen in many previous reports. Treating SJS-TEN with systemic agents
      including cyclosporine will remaincontroversial because the vast majority of data
      comes from case reports, case series, or small open prospective trials.

PMID- 29469761
TI  - Schnitzler syndrome in a patient with a family history of monoclonal gammopathy.
AB  - Schnitzler syndrome is a rare disease characterized by chronic urticaria and a
      monoclonal gammopathy, most commonly IgM with light chains of the kappa type.
      There are currently no known risk factorsassociated with development of the
      disease. We report a case of Schnitzler syndrome in a 48-year-old man with a
      family history of monoclonal gammopathies. The patient's disease has been well
      controlled with anakinra therapy. Our case may contribute to a better
      understanding of the etiology of Schnitzler syndrome as his history could suggest
      a hereditarypredisposition for the disease. Further studies are necessary to
      determine whether a genetic component of Schnitzler syndrome exists, as first
      degree relatives of patients with monoclonal gammopathies may be at risk for the
      development of the disease.

PMID- 29469762
TI  - Anaplastic large cell lymphoma localized to the left breast years after
      radiotherapy for breast cancer.
AB  - Anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma that
      can involve the skin primarily or secondarily. Our case describes an unusual
      presentation of eruptive tumors localized to the leftbreast region several years
      following breast cancer surgery and radiation for carcinoma of the breast. This
      report highlights the challenges in reachingthe diagnosis of an aggressive
      systemic lymphoma presenting on the skin.

PMID- 29469763
TI  - Unusually extensive scalp ulcerations manifested in pemphigus erythematosus.
AB  - Senear-Usher Syndrome, or pemphigus erythematosus, is an autoimmune skin
      blistering disorder with an overlapping clinical presentation of pemphigus
      foliaceus and lupus erythematosus. Lesions typically involve the scalp, face, and
      upper chest or back. This case study focuses on a patient who presentedwith
      progressive scalp ulcers, hyperpigmentation, and eroded plaques with overlying
      hemorrhagic crust. Pemphigus erythematosus was diagnosedwith direct
      immunofluorescence, demonstrating immunoglobulin G and complement deposition both
      intercellularly and at the dermoepidermal junction. The patient is continuing
      treatment with systemicsteroids and steroid-sparing immunosuppressants.

PMID- 29469764
TI  - Focal linear elastosis in a patient with joint hypermobility syndrome.
AB  - Focal linear elastosis (FLE) is a benign skin findingcharacterized by
      hypertrophic linear plaques withabnormal elastic fibers on histology. We present
      aunique case in which focal linear elastosis occurredin the setting of joint
      hypermobility syndrome(JHS). Our patient, a 20-year-old man with a medicalhistory
      significant for symptoms consistent with JHS,had been followed by the
      rheumatology clinic formany months. He was referred to the dermatologydepartment
      for further evaluation of asymptomaticlongitudinal bands on his back that had
      been presentfor many years. He denied trauma but endorsed ahistory of 'stretch
      marks.' On examination there werenumerous horizontally oriented, firm, linear,
      yellowto flesh colored bands, all non-tender to palpation.Punch biopsies were
      performed of involved anduninvolved skin. Histopathology of normal skinrevealed
      no significant abnormalities whereasinvolved skin demonstrated broadened
      collagenbundles in the deep dermis. The elastic fiber stain,Verhoeff-Van Gieson,
      revealed a gross increase in thenumber of elastic fibers, fragmented fibers,
      fiberswith "paintbrush" or widened-ends, fibers of varyingthickness, and clumped
      fibers. This combination ofhistopathologic and clinical features was consistent
      with FLE.

PMID- 29469765
TI  - Nivolumab reactivation of hypertrophic lichen planus, a case report and review of
      published literature.
AB  - We report a case of nivolumab-induced lichen planus (LP) reactivation that was
      previously in remission following chemotherapy for non-smallcelllung cancer
      (NSCLC). Chemotherapy-induced immunosuppression allowed for complete resolution
      of the patient's pre-existing LP, a T-cell mediatedautoimmune process. When the
      patient was switched to nivolumab immunotherapy owing to progression of NSCLC, PD
      1 inhibition led to an overwhelming T-cell response that seemed to have provoked
      a severe LPreactivation. Although lichenoid reactions have been reported with
      nivolumab, to our knowledge, this is the first reported case of nivolumab
      monotherapycausing LP reactivation in a patient with a strong personal and family
      history of the disease that was previously in remission after chemotherapy.

PMID- 29469766
TI  - Herpes zoster as a cause of atypical chronic ulcerations associated with
      tofacitinib.
AB  - Tofacitinib is a targeted inhibitor of janus kinase (JAK), currently approved for
      the treatment of rheumatoid arthritis. We present a patient on treatment
      withtofacitinib who had an episode of classic dermatomal herpes zoster followed
      months later by atypical chronic cutaneous ulcers also caused by herpes zoster.

PMID- 29469767
TI  - Eosinophilic infiltrate resembling eosinophilic cellulitis (Wells syndrome) in a
      patient with mycosis fungoides.
AB  - Mycosis fungoides (MF) is a T-cell, non-Hodgkin lymphoma that primarily involves
      the skin. Extracutaneous involvement, such as in the parotidgland, is
      characteristic of end-stage disease. Eosinophilic cellulitis, or Wells syndrome,
      is a rare inflammatory dermatitis that involves a dermal infiltrate of
      eosinophils. We report a case of an 80-year-old man with a long-standing
      diagnosis of stage IIB MF who acutely developed parotid gland involvement and
      marked hypereosinophilia that most likely represented eosinophilic cellulitis.
      Activated T cells from his MF were likely a trigger factor for the development of
      his eosinophilic cellulitis. To our knowledge, this is the first reported case of
      an MF patient with atypical parotid gland involvement andeosinophilic cellulitis.

PMID- 29469768
TI  - A novel association of pseudoainhum and epidermolytic ichthyosis, successfully
      treated with full thickness skin graft after failed z-plasty repair.
AB  - Pseudoainhum is a rare constriction band variant thatmay progress to spontaneous
      digital strangulationand auto-amputation. Although its association
      withpalmoplantar keratodermas is well established, ithas not been reported in
      conjunction with classicepidermolytic ichthyosis. We describe the first suchcase
      in a 25-year-old woman who presented witha painful constricting band of the fifth
      toe. We alsodescribe her treatment course, which consisted ofa failed z-plasty,
      the traditional therapeutic optionfor acute pseudoainhum, and report the success
      ofsubsequent full thickness skin graft, suggesting thebenefit of this procedure
      as a therapeutic alternativefor patients with pseudoainhum.

PMID- 29469770
TI  - Interstitial granulomatous dermatitis in a patient with chronic hepatitis C and
      mixed cryoglobulinemia.
AB  - A 55-year-old man presented with a history of asymptomatic, bilateral, figurate
      dermatosis consisting of erythematous, annular, linear, andarciform, indurated
      nodules and plaques on the lateral walls of thorax, flanks, and hypogastrium. His
      medical history was positive for chronic hepatitis C. Skin biopsy was compatible
      with the diagnosisof interstitial granulomatous dermatitis.
      Additionalinvestigation revealed positive rheumatoid factor, antinuclear
      antibodies, and cryoglobulins. Thepatient started treatment with high-potency
      topical corticosteroid. After 12 weeks of treatment there was a partial clinical
      improvement of thedermatosis. Interstitial granulomatous dermatitis exhibits a
      distinct histopathological pattern with a diverse clinical appearance, which can
      be associated with autoimmune systemic diseases, neoplasms, several drugs, and
      infections. Optimal therapy for this condition is yet to be established, but
      topical corticosteroids have been a mainstay of treatment.

PMID- 29469769
TI  - ?
AB  - La practica de tatuajes tienen mas de 8000 anos de antiguedad, existiendo un
      incremento continuo en la sociedad occidental en las ultimos 3 decadas La
      introduccion de una sustancia exogena en la pielpuede provocar una respuesta
      inmunologica en su contra, estando descritas reacciones cutaneas por
      hipersensibilidad a una variedad de pigmentos, las que se limitan al area de un
      determinado color,atribuyendose a los materiales inyectados. El color mas
      reportado en la literatura es el rojo, que tradicionalmente se confeccionaban a
      base dederivados del mercurio (cinabrio). Diversos patrones histologicos de
      reaccion estan descritos, siendo el mas frecuente el liquenoide. Presentamos una
      serie de 10 pacientes con reaccion de hipersensibilidad a tatuaje rojo, con
      patron histologico predominante dereaccion granulomatosa y con moderada respuesta
      a tratamiento. Es importante cuando se esta ante un patron granulomatoso de
      reaccion descartar sarcoidosis sistemica e infecciones por micobacterias.

PMID- 29469771
TI  - Clear cell papulosis: report and review.
AB  - A 12-month-old boy presented with three months of asymptomatic hypopigmented flat
      topped papules on the suprapubic skin and lower abdomen. Emollients and topical
      steroids offered no improvementand the patient was referred to the dermatology
      department. Shave biopsy revealed a papillated epidermis with scattered solitary
      mononuclearclear cells at all levels of the epidermis and an overlying basket
      weave orthokeratosis. The cells were epithelioid with increased amphophilic
      cytoplasm. Immunohistochemical staining was positive for CK7,CEA, and CAM5.2 and
      negative for S100, CD1a, and Mart-1. These findings were consistent with clear
      cell papulosis. No treatment was recommended as these lesions were asymptomatic.
      However, yearlyfollow up was recommended given the resemblance of these cells to
      those of Paget disease. Review of the literature demonstrates a total of 31
      biopsy confirmed cases with AE1, CEA, and EMA positivity and S100negativity as
      the most consistent staining properties. A recent retrospective review of 19
      cases documents long term follow-up of at least six years and up to 21 years. The
      results suggested a tendency toward selfresolution and an absence of malignant
      progression, supporting the benign nature of these lesions.

PMID- 29469772
TI  - Precalcaneal congenital fibrolipomatous hamartoma.
AB  - Precalcaneal congenital fibrolipomatous hamartoma is a benign condition of
      infancy that is sometimes misdiagnosed due to lack of reports in the literature.
      Lesions usually present with painless, non-pruritic, skin colored bilateral,
      solitary, symmetric nodules located in the middle of the heels. The lesions
      gradually increase in size and then regress by the age of 2 to3 years old.

PMID- 29469773
TI  - Adult blaschkolinear acquired inflammatory skin eruption (BLAISE) with
      simultaneous features of lichen striatus and blaschkitis.
AB  - Blaschkitis and lichen striatus are generally distinguished in the literature by
      the age of onset, lesion distribution, and histopathology. However, there is
      currently no clear consensus among authors about whether to consider blaschkitis
      and lichen striatus different clinical entities or a spectrum ofthe same disease.
      We present a case of adult BLAISE with features of both lichen striatus and
      blaschkitis, which seems to support the theory that these clinical entities may
      in fact represent a spectrum of the same pathological process.

PMID- 29469775
TI  - Coexistence of keloids and pilomatricoma in a patient with Rubinstein-Taybi
      syndrome.
AB  - Rubinstein-Taybi syndrome (RTS) is an autosomaldominant hereditary disease, which
      contains many skeletal and organ anomalies as well as mental retardation.
      Although high incidence of keloids in RTS is known, it is difficult to find a
      detailed report on the clinical features of keloids. In the following letter, we
      report an RTS patient fulfilling diagnostic criteria whosuffered from both
      keloids and pilomatricoma. We also performed a literature search, which
      identified the possible involvement of the Wnt/beta-catenin signaling pathway in
      the pathogenesis of these two skin lesions.

PMID- 29469776
TI  - Phytophotodermatitis related to carrot extract-containing sunscreen.
AB  - Phytophotodermatitis is a clinical diagnosis from phototoxicity of the skin
      induced by contact with plants or their extracts. Phytophotodermatitis maypresent
      with burning, erythema, patches, plaques, vesicles, bullae, or hyperpigmented
      patches in welldemarcated and unusual shapes. Inquiring about occupation,
      hobbies, and plant or plant extract contact is essential to establishing the
      diagnosis. Herein we present a case of phytophotodermatitisafter use of carrot
      extract-containing sunscreen presenting as a hyperpigmented patch in a geometric
      distribution with accentuation of pigment within the dynamic rhytides.

PMID- 29469777
TI  - Hormonal therapies for hidradenitis suppurativa: Review.
AB  - Hidradenitis suppurativa is a recurrent inflammatory skin condition characterized
      by abscesses and boils, predominantly in the groin, armpit, and buttocks areas.
      HS is not a life-threatening condition, but severely impairs quality of life in
      those affected. Finding a successful treatment approach for HS has been
      challenging, in part because of the lack of a gold-standard treatment method,
      limited research-based information, and the nature of clinical variation in the
      disease. Treatment commonly consists of antibiotics, anti-inflammatory therapy,
      hormonal therapy, and more invasive clinical procedures. Treatment is chosen by
      the degree of severity by which the condition presents and is modified
      accordingly. This review describes the roles of hormones in the pathogenesis of
      hidradenitis suppurativa and describes the use of hormonal therapy such as,
      finasteride, dutasteride, spironolactone, and oral contraceptives. The outcomes
      of the use of these modalities in various clinical studies are summarized.

PMID- 29469778
TI  - Incorporating social media into dermatologic education.
AB  - In the current digital age, medical education has slowly evolved from the largely
      lecture-based teaching style of the past to incorporate more interactive
      pedagogical techniques, including use of social media. Already used readily by
      millennial trainees and clinicians, social media can also be used in innovative
      ways to teach trainees and facilitate continuing education among practicing
      clinicians. In this commentary, we discuss many learning benefits of social media
      and review potential pitfalls of employing social media in both trainee and
      physician dermatological education.

PMID- 29469779
TI  - Cutaneous infection due to Mycobacterium immunogenum: an European case report and
      review of the literature.
AB  - (no more than 200 words): In the last few years, the incidence of cutaneous
      infections caused by nontuberculous mycobacteria is increasing. Since
      Mycobacterium immunogenum was first described in 2001, few case reports have been
      described, all of them in the American continent. We report a case with cutaneous
      infection caused by this newly discovered NTB in Europe.A 65-year-old woman
      presented with a 3-months history of pruritic lesions on abdomen. Examination
      revealed erythematous inflammatory papules, pustules, and crusts. Three weeks
      later, mycobacteria were cultured from the biopsy specimen. Mycobacterium
      immunogenum was identified based on susceptibility test results and polymerase
      chain reaction (PCR) restriction enzyme analysis. Treatment with clarithromycin
      was started. M. immunogenum is a nontuberculous mycobacterium that was first
      described by Wilson et al. in 2001 as a rapidly growing variety and new species
      in the Mycobacterium chelonae-Mycobacterium abscessus group. PCR-restriction
      analysis of a 439-bp segment of the hsp65 gene and/or sequencing the species
      specific region of the 16S rDNA can confirm this new species. Since the
      description of M. immunogenum, 8 clinical case reports have been published, most
      involving cutaneous infections and all of them in the American continent. We
      present a case of cutaneous infection caused by M. immunogenum in a Spanish
      woman.

PMID- 29469780
TI  - Non-dermatomal varicella-zoster skin infection: disseminated cutaneous herpes
      zoster without dermatome in an immunosuppressed woman.
AB  - Disseminated herpes zoster is defined as the presence of more than 20 lesions
      outside the dermatome. This unusual presentation is more common in
      immunosuppressed patients. Complications such as hepatitis, encephalitis, and
      pneumonitis are more likely in individuals with disseminated varicella zoster
      virus infection.A 63-year-old woman being treated for breast cancer developed
      multiple pustules and vesicles days after starting doxorubicin and
      cyclophosphamide chemotherapy. Ten individual lesions appeared on her chest,
      abdomen, back, and leg. Non-dermatomal disseminated herpes zoster was suspected.
      She was treated with oral antiviral therapy, as well as with oral and topical
      antibiotics. Varicella zoster virus infection was confirmed by direct fluorescent
      antibody staining. After one month, her skin lesions had resolved and she resumed
      chemotherapy.In a setting of immunosuppression, the rare presentation of
      disseminated herpes zoster without dermatome should be considered. Appropriate
      antiviral therapy should be administered while waiting for confirmation of the
      diagnosis, so as to reduce the risk of visceral dissemination of the varicella
      zoster virus infection.

PMID- 29469781
TI  - Ponatinib-induced ichthyosiform drug eruption: insights into acquired ichthyosis.
AB  - Cutaneous adverse events are commonly experienced with use of tyrosine kinase
      inhibitors in the treatment of leukemia and typically include nonspecific
      cutaneous eruptions and xerosis. We report the case of a man who experienced an
      ichthyosiform drug eruption while taking ponatinib, a third-generation tyrosine
      kinase inhibitor. Disruption of epidermal growth pathways through inhibition of
      various receptor tyrosine kinases by ponatinib may offer insights into the
      pathophysiologic mechanisms behind acquired ichthyosis.

PMID- 29469782
TI  - Rapidly fatal metastatic cutaneous angiosarcoma initially mimicking a furuncle in
      a middle-aged male.
AB  - Cutaneous angiosarcomas are rare but typically occur in three distinct clinical
      settings and are most commonly found on the scalp or face of elderly men.
      Positive prognostic factors include tumor size less than 5 cm, primary tumor
      location below the head, negative margins after excision, resectability, and
      younger age. Metastases drastically reduce survival and the most common
      metastatic site is lung. We present a 43-year-old man who had primary cutaneous
      angiosarcoma that initially mimicked a furuncle and eventuated in multiple
      metastases. The metastatic disease included brain involvement, which has rarely
      been reported, especially in a relatively young person without known predisposing
      conditions. This unique case also highlights the need for early diagnosis
      followed by advanced imaging, given the limitations of current therapies and high
      metastatic potential of angiosarcoma.

PMID- 29469783
TI  - Delayed presentation of toxic epidermal necrolysis-like cutaneous acute graft
      versus-host disease in the setting of recent immunosuppressant discontinuation.
AB  - Acute graft-versus-host disease (GvHD) is a process that classically has been
      defined as occurring less than 100 days after stem cell transplant. When Stage IV
      cutaneous acute GvHD occurs outside this window, it can be difficult to
      distinguish clinically from toxic epidermal necrolysis (TEN). A 50-year-old man
      with diffuse large B-cell lymphoma who had undergone an allogeneic stem cell
      transplant 20 months previously was admitted for neutropenic septic shock. He
      developed a slowly progressing macular/papular eruption with multiple tender
      bullae found to be consistent with TEN-like Stage IV cutaneous acute GvHD on
      biopsy. It was discovered that the patient's maintenance immunosuppression had
      been completely discontinued one month prior to admission in preparation for
      clinical trial enrollment, causing a late presentation of cutaneous acute GvHD.
      This case provides particular insight into the diagnosis and management of late
      presenting acute GvHD given that it is the first reported case of Stage IV
      cutaneous acute GvHD more than 12 months after stem cell transplant. In the
      setting of decreased immunosuppression in a patient with a history of a stem cell
      transplant, acute graft-versus-host disease must be considered regardless of the
      time that has elapsed since transplant.

PMID- 29469784
TI  - A case of erythema multiforme major following administration of ciprofloxacin
      ophthalmic drops.
AB  - A 49-year old woman was hospitalized for generalized rash and pruritus following
      the administration of ophthalmic drops containing ciprofloxacin to treat
      conjunctivitis. Physical examination demonstrated diffuse erythematous papules
      and plaques with a targetoid appearance, injected sclera, and multiple erosions
      in the oropharynx. Skin biopsy confirmed a diagnosis of erythema multiforme
      major. The eye drops were discontinued and supportive treatment was initiated;
      the patient recovered in four weeks and was discharged from the hospital.
      Although cases such as this are rare, it is important that physicians take a
      thorough medication history from all patients with suspected erythema multiforme,
      including topical and ophthalmic medications. Prompt discontinuation of the
      offending agent can hasten patient recovery and optimize outcomes.

PMID- 29469785
TI  - Pemphigus foliaceus worsened by drugs in a patient with psoriasis, responding to
      adalimumab.
AB  - Pemphigus foliaceus is a blistering autoimmune disease related to the production
      of autoantibodies against desmoglein 1. We present a patient with psoriasis and
      pemphigus foliaceus aggravated by enalapril and amlodipine intake, with
      successful response of both conditions to adalimumab therapy.

PMID- 29469786
TI  - Primary vulvar Paget disease - the importance of clinical suspicion.
AB  - Extramammary Paget disease of the vulva is a rare condition that accounts for
      only 1-2% of vulvar malignancies and represents a frequent cause of misdiagnosis.
      It is most commonly seen in postmenopausal women. Clinically it is similar to
      Paget disease of the breast, appearing as red, well-demarcated eczematoid
      lesions, with slightly raised edges. A high degree of clinical suspicion is very
      important when evaluating these lesions in order to avoid misdiagnosis and delay
      of effective treatment. We present a case of vulvar Paget disease treated with
      vulvectomy.

PMID- 29469787
TI  - Telangiectasia macularis eruptiva perstans associated with a sicca complex.
AB  - We present the case of woman in her 50s who developed numerous red-brown
      telangiectatic macules on her trunk and extremities, as well as persistent dry
      eyes and dry mouth. Skin biopsy was consistent with telangiectasia macularis
      eruptiva perstans (TMEP). Serum tryptase was elevated suggesting systemic
      involvement. Anti-Ro and La were negative. ANA was positive. Salivary gland
      biopsy revealed a focus score of 3 and immunostains revealed infiltrates of
      aberrant CD117 positive mast cells. This case suggests a mechanistic role of
      mastocytosis in salivary compromise.

PMID- 29469788
TI  - Erythematous asymptomatic nodule on the sole.
AB  - A 75-year-old man presented to the dermatology clinic with an asymptomatic lesion
      on his right plantar surface. The lesion had progressively grown for two months.
      Physical examination revealed an erythematous and slightly scaly nodule measuring
      10x10 mm. Dermoscopy examination showed central diffuse erythema with small red
      globules. A punch-biopsy revealed a proliferation of irregularly branched small
      vessels with collapsed lumen, extending in an infiltrative pattern in the
      superficial and deep dermis. Although this is a rare location, a diagnosis of
      microvenular hemangioma was made.

PMID- 29469789
TI  - Paquidermodactilia, engrosamiento digital proximal. Pachydermodactyly, digital
      proximal thickening.
AB  - We report a case of pachydermodactyly (PDD). PDD is a benign, asymptomatic soft
      tissue swelling affecting the skin of the lateral aspects of the proximal
      interphalangeal joints of the fingers, mostly in young adolescent males. It has
      often been interpreted as a consequence of tic-like behavior as part of an
      obsessive-compulsive disorder. Although the diagnosis is essentially clinical,
      skin biopsy shows compact orthokeratotic hyperkeratosis, increased numbers of
      collagen fibers and fibroblasts, and no inflammatory changes. A rapid clinical
      recognition of PDD should avoid many unproductive and expensive diagnostic tests.

PMID- 29469790
TI  - Jessner lymphocytic infiltration - rare in childhood.
AB  - We present a 13-year-old girl with Jessner lymphocytic infiltrate of the skin,
      who has suffered from the disease since the age of 9 years. It is a rare disease
      in childhood, and we highlight the clinical features and therapeutic response of
      tacrolimus.

PMID- 29469791
TI  - Hyperkeratotic and hypertrophic lichen nitidus.
AB  - Lichen nitidus typically presents as shiny pin-head sized papules on the trunk
      and extremities, often affecting children and young adults. In this prototypical
      form, it rarely presents a diagnostic challenge being characterized by
      distinctive clinical and histopathologic findings. We describe a rare variant of
      lichen nitidus, which we term "hyperkeratotic and hypertrophic lichen nitidus."

PMID- 29469792
TI  - Kimura disease.
AB  - Kimura disease is a rare, benign, chronic, immune-mediated inflammatory disorder.
      We report a 46-year-old man who presented with a cutaneous nodule behind his left
      ear. Surgical removal of the growth confirmed the histological diagnosis of KD.
      There was no recurrence found after 3 years follow-up.

PMID- 29469793
TI  - Lesiones subcutaneas dolorosas en paciente con melanoma metastasico: un caso de
      paniculitis linfocitica asociado a vemurafenib.
AB  - Vemurafenib ha probado ser una herramienta util en el tratamiento de melanoma
      metastasico con mutacion BRAF-V600E. Los efectos adversos incluyen artralgias,
      fatiga y toxicidad cutanea, siendo infrecuente la paniculitis. Presentamos el
      caso de una paciente de 43 anos con melanoma metastasico que desarrolla lesiones
      subcutaneas dolorosas en miembros inferiores y superiores, asociadas a clinica
      sistemica despues de 2 semanas de inicio de tratamiento con Vemurafenib +
      Cobimetinib. La histologia demostro paniculitis linfocitaria septal y lobulillar.
      La paciente tuvo mala tolerancia al tratamiento anti diana a dosis plenas,
      requiriendo su ajuste, generando una corticodependencia para controlar
      sintomatologia, y que finalmente obligo a la descontinuacion de la terapia
      dirigida contra melanoma.  A la fecha, se han descrito 29 casos en la literatura
      de paniculitis asociada a vemurafenib, siendo la mayoria paniculitis
      neutrofilicas con adecuado control de sintomatologia asociando antiinflamatorios
      no esteroidales y/o corticoides orales sin requerir en su mayoria modificacion de
      la terapia contra melanoma; sin embargo hay que tener presente que pueden haber
      casos con mala evolucion que obligan a la reduccion de dosis de vemurafenib y
      descontinuar el tratamiento, como ha ocurrido en nuestro reporte.Vemurafenib has
      proven to be a useful tool in the treatment of metastatic melanoma with BRAF
      V600E mutation. Adverse effects include arthralgia, fatigue, and skin toxicity;
      panniculitis is a rare complication. We present the case of a 43-year-old patient
      with metastatic melanoma who developed painful subcutaneous nodules of the lower
      and upper limbs and associated systemic clinical symptoms after 2 weeks of
      treatment with vemurafenib plus cobimetinib. Histology showed a septal and
      lobular lymphocytic panniculitis.The patient had poor tolerance of the full-dose
      treatment, requiring its adjustment. Systemic corticosteroids were required to
      control symptomatology, which finally forced the discontinuation of the
      medication.To date, 29 cases have been described in the literature of
      panniculitis associated with vemurafenib. Most of these have been neutrophilic
      panniculitis, but adequate control of symptoms is usually achieved with
      nonsteroidal anti-inflammatory drugs and/or oral corticosteroids without
      requiring modification of melanoma therapy. However, it must be borne in mind
      that there may be cases that force the reduction and discontinuation
      ofvemurafenib treatment. We believe that this histological variant of lymphocytic
      panniculitis and its poor response to decrease in vemurafenib makes this case
      unusual and instructive.

PMID- 29469794
TI  - Inflamed actinic keratoses associated with pemetrexed and carboplatin therapy.
AB  - Eruptive actinic keratosis (AK) consequent to systemic chemotherapy can be
      confused with drug allergies. We present the first case of inflamed AKs in one
      patient after receiving combination therapy with pemetrexed and carboplatin.A 68
      year-old woman with non-small cell lung adenocarcinoma (NSCLC) presented with
      numerous pruritic ill-defined, gritty, erythematous papules consistent with AKs
      on her upper chest, upper back, and arms two weeks after completing the first
      cycle of combination therapy with carboplatin and pemetrexed. The care team
      managed her with topical steroids and the lesions resolved within one month. The
      patient resumed the second cycle of chemotherapy and reported the occurrence of a
      similar but milder eruption.This case illustrates that eruptive AKs should be
      considered in the differential diagnosis of drug-related rashes, especially if
      the physical exam is suggestive. The mainstay of treatment should be directed at
      symptomatic improvement, and chemotherapy may be continued.

PMID- 29469795
TI  - Eritema anular eosinofilico en un adulto Eosinophilic anular erythema in an
      adult.
AB  - Eosinophilic annular erythema (EAE) is an uncommon eosinophilic dermatosis.
      Clinically it is characterized by recurrent episodes of annular or figurative
      plaques. The histopathological study shows a perivascular inflammatory infiltrate
      in the superficial and deep dermis, composed of lymphocytes and eosinophils. It
      was originally described in children. We report an adult woman who presented with
      recurrent erythematous annular plaques on the trunk and extremities. A biopsy
      showed a mainly perivascular lymphocytic infiltrate with numerous eosinophils in
      the dermis. Laboratory examinations revealed subclinical hypothyroidism. The
      lesions resolved with topical corticosteroid spontaneously after 3 months.

PMID- 29469796
TI  - Trends in unsolicited dermatologic opinions: a national survey.
AB  - In dermatology, a particularly common ethical dilemma can arise when the skin
      lesions of bystanders are inadvertently viewed in public settings. Dermatology is
      a unique field, where a person's organ of interest is readily visible to others.
      When lesions are suspicious for skin disease, unsolicited medical opinions may or
      may not be given depending on several factors. This study examined the actions
      and attitudes of dermatologists with different levels of experience through the
      use of case scenarios with various settings and skin lesions.

PMID- 29469797
TI  - A gastronomic delight?
AB  - Flagellate dermatitis (FD) exhibits a striking clinical appearance similar to
      whiplash marks. General dermatologists are likely to encounter this clinical
      appearance as a more localized presentation of phytophotodermatosis. Jellyfish
      stings may also cause localized linear or FD. Chemotherapeutic agents such as
      bleomycin, doxorubicin, docetaxel, and trastuzumab are well-recognized causes of
      a widespread FD and it may more rarely be seen in connective tissue disease such
      as dermatomyositis or Still disease. In our case, this was a presentation of
      shiitake mushroom dermatitis.

PMID- 29469798
TI  - Complete resolution of erythema elevatum diutinum using oral sulfasalazine.
AB  - Erythema elevatum diutinum (EED) is a rare, chronic small-vessel vasculitis that
      presents as firm, red, violaceous, or brown papules and nodules on the extensor
      surfaces of the limbs. Oral dapsone is considered first-line therapy for EED; in
      the current case report, a patient presenting with EED began dapsone treatment
      and symptoms subsided within two weeks. Seven months later, the patient became
      pregnant and stopped dapsone owing to her concerns with dapsone use during
      pregnancy, resulting in recurrence of EED symptoms. We present a novel treatment
      approach with oral sulfasalazine, which was given to the patient in lieu of
      dapsone and resulted in complete resolution of EED symptoms.

PMID- 29469799
TI  - Complete response of secukinumab in palmoplantar psoriasis.
AB  - Palmoplantar psoriasis is plaque psoriasis involving the palms and soles.
      Palmoplantar psoriasis is a treatment challenge for dermatologists and it is
      difficult to treat with topical and systemic therapies. Owing to its location and
      manifestations, palmoplantar psoriasis is associated with greater pain,
      functional limitations, and significant impairment of health-related quality of
      life. Recently a new biologic agent, secukinumab, has been approved for treatment
      of moderate to severe plaque psoriasis. GESTURE trial is a study of the
      secukinumab clinical development that evaluates efficacy and safety in this
      subpopulation of patients. We present a patient with palmar psoriasis refractory
      to systemic treatments who showed a gradual and complete response to secukinumab
      sustained at week 30 and without adverse events. Our patient had a significant
      improvement in his quality of life and work activity.

PMID- 29469800
TI  - Analysis of population inquiry on practices for ultraviolet radiation protection.
AB  - UV radiation exposure is one of the key modifiable risk factors for skin cancer.
      Hence, patient education regarding skin protection and sunscreen use is of
      tremendous importance to public health. To better understand patient practices
      regarding skin protection in a population level, we looked into the Internet
      search behavior of the US-based population. We investigated patient inquires on
      the United States Food and Drug Administration (FDA) announcements regarding
      sunscreen use by quantifying search terms such as "broad spectrum sunscreen",
      "sunscreen" and "sunblock" with Google Trends, a novel methodology for
      understanding internet search practices. Our findings show that "broad spectrum
      sunscreen" searches were significantly increased post 2011 FDA announcements,
      which suggest increased public awareness regarding the importance of broad
      spectrum protection. It is encouraging these preliminary results indicate that
      skin protection practices are being increasingly investigated by the general
      public and may serve as a novel approach for identifying areas of improvement
      regarding patient education on the reduction of the risk for skin cancer.

PMID- 29469801
TI  - Undisturbed characteristic herpes simplex virus 2 outbreak.
AB  - Herpes simplex virus 2 (HSV-2) is a common sexually transmitted disease that
      typically presents with focal erosions or small vesicles on an erythematous
      base.Herein, a case is described in which a 42-year old man experienced a genital
      HSV-2 outbreak after sustaining a spinal cord injury. No typical prodromal
      symptomswere experienced; therefore the vesicular lesions remained completely
      intact, granting an unusual opportunity to visualize herpetic infection in its
      most classic morphology.

PMID- 29469802
TI  - Nail or plate in the management of distal extra-articular tibial fracture, what
      is better? Valutation of outcomes.
AB  - INTRODUCTION: Distal tibial fractures are the most common long bone fractures.
      Several studies focusing on the methods of treatment of displaced distal tibial
      fractures have been published. To date, locked plates, intramedullary nails and
      external fixation are the three most used techniques. The aim of our study was to
      compare intramedullary nail (IMN) and locked plate (LP) for treatment of this
      kind of fracture. MATERIALS AND METHODS: We collected data on 81 patients with
      distal tibial fractures (distance from the joint between 40 and 100 mm) and we
      divided into two groups: IMN and LP. We compared in the 2 groups the mean
      operation time, the mean union time, the infection rate the rate of malunion and
      nonunion, the full weight bearing time. RESULTS: No patient in the two groups
      developed a nonunion. None of the patients obtained a fair or poor outcome.
      Overall 52 patients obtained an excellent result (69.3%) and 23 obtained a good
      result (30.6%). DISCUSSION: Our study results indicate a superiority of IMN over
      LP in terms of lower rates of infections and statistically significant shorter
      time to full weight bearing. Whereas LP appeared to be advantageous over IMN in
      terms of leading to a better anatomical and fixed reductions of the fracture and
      a lower rate of union complications. The two treatments achieved comparable
      results in terms of operation time, hospital stay, union time and functional
      outcomes.

PMID- 29469803
TI  - Use of the HemiCAP partial hip resurfacing technique for traumatic femoral head
      osteochondral defects following obturator hip dislocations.
AB  - Fracture of the femoral head (OTA 31-C1.3) following anterior obturator
      dislocations are a challenging problem as the fractures are often communited,
      impacted and with loose osteochondral fragments, making surgical fixation
      difficult. This can result in residual articular defects if the fragments cannot
      be internally fixed and need be excised, predisposing to secondary
      osteoarthritis. Treatment options for these defects are limited, have variable
      results and with limited literature to guide us on outcomes due to the rarity of
      these injuries. Here, we describe the first use of the technique of partial
      femoral head resurfacing in two patients with such fractures and report on their
      long term outcomes.

PMID- 29469804
TI  - Early results of total hip arthroplasty using dual-mobility cup in patients with
      osteonecrosis of the femoral head.
AB  - INTRODUCTION: Osteonecrosis of the femoral head (ONFH) remains a therapeutic
      challenge for patients undergoing total hip arthroplasty (THA). The majority of
      these patients are young with high functional demand, and show an increased risk
      of dislocation following surgery than patients with osteoarthritis. The use of
      double mobility cup (DMC) has been linked with lower rates of complications when
      compared to conservative cups; however, the literature is scarce over DMC results
      in patients with ONFH. The aim of the study is to report the early outcomes of
      patients with ONFH treated with THA-DMC. MATERIALS: A retrospective analysis of
      patients suffering from ONFH who underwent THA using DMC (THA-DMC) from 2006 to
      2015 were evaluated for functional status and risk of post-operative
      complications. Thirty THA-DMC in 26 patients with a mean follow-up of 51 months
      were evaluated clinically (modified Hip Harris Score) and radiologically.
      RESULTS: The mean age of the included patients was 54.9 years. At final follow
      up, the mean modified Hip Harris score was 98.7 +/- 2.7 and no dislocation
      episodes or revision surgeries were recorded. The radiological assessment
      revealed no signs of migration/tilting, radiolucent lines, periprosthetic
      osteolysis or heterotopic ossification over the DMC component and the femoral
      stem. The survival rate over 51 months of follow-up was 100%. DISCUSSION: The use
      of the new generation of dual mobility cup in patients with ONFH showed excellent
      functional early results with no major complications such as dislocation.

PMID- 29469805
TI  - C/EBPdelta drives interactions between human MAIT cells and endothelial cells
      that are important for extravasation.
AB  - Many mediators and regulators of extravasation by bona fide human memory
      phenotype T cells remain undefined. Mucosal-associated invariant T (MAIT) cells
      are innate-like, antibacterial cells that we found excelled at crossing inflamed
      endothelium. They displayed abundant selectin ligands, with high expression of
      FUT7 and ST3GAL4, and expressed CCR6, CCR5, and CCR2, which played non-redundant
      roles in trafficking on activated endothelial cells. MAIT cells selectively
      expressed CCAAT/enhancer-binding protein delta (C/EBPdelta). Knockdown of
      C/EBPdelta diminished expression of FUT7, ST3GAL4 and CCR6, decreasing MAIT cell
      rolling and arrest, and consequently the cells' ability to cross an endothelial
      monolayer in vitro and extravasate in mice. Nonetheless, knockdown of C/EBPdelta
      did not affect CCR2, which was important for the step of transendothelial
      migration. Thus, MAIT cells demonstrate a program for extravasastion that
      includes, in part, C/EBPdelta and C/EBPdelta-regulated genes, and that could be
      used to enhance, or targeted to inhibit T cell recruitment into inflamed tissue.

PMID- 29469806
TI  - MreB filaments align along greatest principal membrane curvature to orient cell
      wall synthesis.
AB  - MreB is essential for rod shape in many bacteria. Membrane-associated MreB
      filaments move around the rod circumference, helping to insert cell wall in the
      radial direction to reinforce rod shape. To understand how oriented MreB motion
      arises, we altered the shape of Bacillus subtilis. MreB motion is isotropic in
      round cells, and orientation is restored when rod shape is externally imposed.
      Stationary filaments orient within protoplasts, and purified MreB tubulates
      liposomes in vitro, orienting within tubes. Together, this demonstrates MreB
      orients along the greatest principal membrane curvature, a conclusion supported
      with biophysical modeling. We observed that spherical cells regenerate into rods
      in a local, self-reinforcing manner: rapidly propagating rods emerge from small
      bulges, exhibiting oriented MreB motion. We propose that the coupling of MreB
      filament alignment to shape-reinforcing peptidoglycan synthesis creates a locally
      acting, self-organizing mechanism allowing the rapid establishment and stable
      maintenance of emergent rod shape.

PMID- 29469807
TI  - GRAM domain proteins specialize functionally distinct ER-PM contact sites in
      human cells.
AB  - Endoplasmic reticulum (ER) membrane contact sites (MCSs) are crucial regulatory
      hubs in cells, playing roles in signaling, organelle dynamics, and ion and lipid
      homeostasis. Previous work demonstrated that the highly conserved yeast Ltc/Lam
      sterol transporters localize and function at ER MCSs. Our analysis of the human
      family members, GRAMD1a and GRAMD2a, demonstrates that they are ER-PM MCS
      proteins, which mark separate regions of the plasma membrane (PM) and perform
      distinct functions in vivo. GRAMD2a, but not GRAMD1a, co-localizes with the E
      Syt2/3 tethers at ER-PM contacts in a PIP lipid-dependent manner and pre-marks
      the subset of PI(4,5)P2-enriched ER-PM MCSs utilized for STIM1 recruitment. Data
      from an analysis of cells lacking GRAMD2a suggest that it is an organizer of ER
      PM MCSs with pleiotropic functions including calcium homeostasis. Thus, our data
      demonstrate the existence of multiple ER-PM domains in human cells that are
      functionally specialized by GRAM-domain containing proteins.

PMID- 29469810
TI  - Design and analysis of coiled fiber reinforced soft pneumatic actuator.
AB  - Fiber reinforced elastomeric enclosures (FREEs) are soft pneumatic actuators that
      can contract and generate forces upon pressurization. Typical engineering
      applications utilize FREEs in their straight cylindrical configuration and derive
      actuation displacement and forces from their ends. However, there are several
      instances in nature, such as an elephant trunk, snakes and grapevine tendrils,
      where a spiral configuration of muscle systems is used for gripping, thereby
      establishing a mechanical connection with uniform force distribution. Inspired by
      these examples, this paper investigates the constricting behavior of a
      contracting FREE actuator deployed in a spiral or coiled configuration around a
      cylindrical object. Force balance is used to model the blocked force of the FREE,
      which is then related to the constriction force using a string model. The
      modeling and experimental findings reveal an attenuation in the blocked force,
      and thus the constriction force caused by the coupling of peripheral contact
      forces acting in the spiral configuration. The usefulness of the coiled FREE
      configuration is demonstrated in a soft arm orthosis for crutch users that
      provides a constriction force around the forearm. This design minimizes injury
      risk by reducing wrist load and improving wrist posture.

PMID- 29469808
TI  - Rab5 and Alsin regulate stress-activated cytoprotective signaling on
      mitochondria.
AB  - Mitochondrial stress response is essential for cell survival, and damaged
      mitochondria are a hallmark of neurodegenerative diseases. Thus, it is
      fundamental to understand how mitochondria relay information within the cell.
      Here, by investigating mitochondrial-endosomal contact sites we made the
      surprising observation that the small GTPase Rab5 translocates from early
      endosomes to mitochondria upon oxidative stress. This process is reversible and
      accompanied by an increase in Rab5-positive endosomes in contact with
      mitochondria. Interestingly, activation of Rab5 on mitochondria depends on the
      Rab5-GEF ALS2/Alsin, encoded by a gene mutated in amyotrophic lateral sclerosis
      (ALS). Alsin-deficient human-induced pluripotent stem cell-derived spinal motor
      neurons are defective in relocating Rab5 to mitochondria and display increased
      susceptibility to oxidative stress. These findings define a novel pathway whereby
      Alsin catalyzes the assembly of the Rab5 endocytic machinery on mitochondria.
      Defects in stress-sensing by endosomes could be crucial for mitochondrial quality
      control during the onset of ALS.

PMID- 29469811
TI  - Evaluating the Laplace pressure of water nanodroplets from simulations.
AB  - We calculate the components of the microscopic pressure tensor as a function of
      radial distance r from the centre of a spherical water droplet, modelled using
      the TIP4P/2005 potential. To do so, we modify a coarse-graining method for
      calculating the microscopic pressure (Ikeshoji et al 2003 Mol. Simul. 29 101) in
      order to apply it to a rigid molecular model of water. As test cases, we study
      nanodroplets ranging in size from 776 to 2880 molecules at 220 K. Beneath a
      surface region comprising approximately two molecular layers, the pressure tensor
      becomes approximately isotropic and constant with r. We find that the dependence
      of the pressure on droplet radius is that expected from the Young-Laplace
      equation, despite the small size of the droplets.

PMID- 29469809
TI  - Efficient and accurate extraction of in vivo calcium signals from microendoscopic
      video data.
AB  - In vivo calcium imaging through microendoscopic lenses enables imaging of
      previously inaccessible neuronal populations deep within the brains of freely
      moving animals. However, it is computationally challenging to extract single
      neuronal activity from microendoscopic data, because of the very large background
      fluctuations and high spatial overlaps intrinsic to this recording modality.
      Here, we describe a new constrained matrix factorization approach to accurately
      separate the background and then demix and denoise the neuronal signals of
      interest. We compared the proposed method against previous independent components
      analysis and constrained nonnegative matrix factorization approaches. On both
      simulated and experimental data recorded from mice, our method substantially
      improved the quality of extracted cellular signals and detected more well
      isolated neural signals, especially in noisy data regimes. These advances can in
      turn significantly enhance the statistical power of downstream analyses, and
      ultimately improve scientific conclusions derived from microendoscopic data.

PMID- 29469812
TI  - Dimethyl methylphosphonate adsorption and decomposition on MoO2 as studied by
      ambient pressure x-ray photoelectron spectroscopy and DFT calculations.
AB  - Organophosphonates range in their toxicity and are used as pesticides,
      herbicides, and chemical warfare agents (CWAs). Few laboratories are equipped to
      handle the most toxic molecules, thus simulants such as dimethyl
      methylphosphonate (DMMP), are used as a first step in studying adsorption and
      reactivity on materials. Benchmarked by combined experimental and theoretical
      studies of simulants, calculations offer an opportunity to understand how
      molecular interactions with a surface changes upon using a CWA. However, most
      calculations of DMMP and CWAs on surfaces are limited to adsorption studies on
      clusters of atoms, which may differ markedly from the behavior on bulk solid
      state materials with extended surfaces. We have benchmarked our solid-state
      periodic calculations of DMMP adsorption and reactivity on MoO2 with ambient
      pressure x-ray photoelectron spectroscopy studies (APXPS). DMMP is found to
      interact strongly with a MoO2 film, a model system for the MoO x component in the
      ASZM-TEDA(c) gas filtration material. Density functional theory modeling of
      several adsorption and decomposition mechanisms assist the assignment of APXPS
      peaks. Our results show that some of the adsorbed DMMP decomposes, with all the
      products remaining on the surface. The rigorous calculations benchmarked with
      experiments pave a path to reliable and predictive theoretical studies of CWA
      interactions with surfaces.

PMID- 29469813
TI  - The W alloying effect on thermal stability and hardening of nanostructured Cu-W
      alloyed thin films.
AB  - In order to achieve desired mechanical properties of alloys by manipulating grain
      boundaries (GBs) via solute decoration, it is of great significance to understand
      the underlying mechanisms of microstructural evolution and plastic deformation.
      In this work, nanocrystalline (NC) Cu-W alloyed films with W concentrations
      spanning from 0 to 40 at% were prepared by using magnetron sputtering. Thermal
      stability (within the temperature range of 200  degrees C-600  degrees C) and
      hardness of the films were investigated by using the x-ray diffraction,
      transmission electron microscope (TEM) and nanoindentation, respectively. The NC
      pure Cu film exhibited substantial grain growth upon all annealing temperatures.
      The Cu-W alloyed films, however, displayed distinct microstructural evolution
      that depended not only on the W concentration but also on the annealing
      temperature. At a low temperature of 200  degrees C, all the Cu-W alloyed films
      were highly stable, with unconspicuous change in grain sizes. At high
      temperatures of 400  degrees C and 600  degrees C, the microstructural evolution
      was greatly controlled by the W concentrations. The Cu-W films with low W
      concentration manifested abnormal grain growth (AGG), while the ones with high W
      concentrations showed phase separation. TEM observations unveiled that the AGG in
      the Cu-W alloyed thin films was rationalized by GB migration. Nanoindentation
      results showed that, although the hardness of both the as-deposited and annealed
      Cu-W alloyed thin films monotonically increased with W concentrations, a
      transition from annealing hardening to annealing softening was interestingly
      observed at the critical W addition of ~25 at%. It was further revealed that an
      enhanced GB segregation associated with detwinning was responsible for the
      annealing hardening, while a reduced solid solution hardening for the annealing
      softening.

PMID- 29469814
TI  - Bifunctional bamboo-like CoSe2 arrays for high-performance asymmetric
      supercapacitor and electrocatalytic oxygen evolution.
AB  - Bifunctional bamboo-like CoSe2 arrays are synthesized by thermal annealing of
      Co(CO3)0.5OH grown on carbon cloth in Se atmosphere. The CoSe2 arrays obtained
      have excellent electrical conductivity, larger electrochemical active surface
      areas, and can directly serve as a binder-free electrode for supercapacitors and
      the oxygen evolution reaction (OER). When tested as a supercapacitor electrode,
      the CoSe2 delivers a higher specific capacitance (544.6 F g-1 at current density
      of 1 mA cm-2) compared with CoO (308.2 F g-1) or Co3O4 (201.4 F g-1). In
      addition, the CoSe2 electrode possesses excellent cycling stability. An
      asymmetric supercapacitor (ASC) is also assembled based on bamboo-like CoSe2 as a
      positive electrode and active carbon as a negative electrode in a 3.0 M KOH
      aqueous electrolyte. Owing to the unique stucture and good electrochemical
      performance of bamboo-like CoSe2, the as-assembled ACS can achieve a maximum
      operating voltage window of 1.7 V, a high energy density of 20.2 Wh kg-1 at a
      power density of 144.1 W kg-1, and an outstanding cyclic stability. As the
      catalyst for the OER, the CoSe2 exhibits a lower potential of 1.55 V (versus RHE)
      at current density of 10 mA cm-2, a smaller Tafel slope of 62.5 mV dec-1 and an
      also outstanding stability.

PMID- 29469815
TI  - Local structure and defects in ion irradiated KTaO3.
AB  - The modification of the local structure in cubic perovskite KTaO3 irradiated with
      3 MeV and 1.1 GeV Au ions is studied by Raman and x-ray absorption spectroscopy,
      complemented by density functional theory (DFT) calculations. In the case of
      irradiation with 3 MeV Au ions where displacement cascade processes are dominant,
      the Ta L3-edge x-ray absorption measurements suggest that a peak corresponding to
      the Ta-O bonds in the TaO6 octahedra splits, which is attributed to the formation
      of TaK antisite defects that are coupled with oxygen vacancies, V O. This finding
      is consistent with the DFT calculations. Under irradiation with 1.1 GeV ions, the
      intense ionization and electronic energy deposition lead to a blue shift and an
      intensity reduction of active Raman bands. In the case of sequential
      irradiations, extended x-ray absorption fine structure measurements reveal a
      decrease in concentration of coupled TaK-V O defects under subsequent irradiation
      with 1.1 GeV Au ions.

PMID- 29469816
TI  - White light emitting device based on single-phase CdS quantum dots.
AB  - White light emitting diodes (WLEDs) based on quantum dots (QDs) are emerging as
      robust candidates for white light sources, however they are suffering from the
      problem of energy loss resulting from the re-absorption and self-absorption among
      the employed QDs of different peak wavelengths. It still remains a challenging
      task to construct WLEDs based on single-phase QD emitters. Here, CdS QDs with
      short synthesis times are introduced to the fabrication of WLEDs. With a short
      synthesis time, on one hand, CdS QDs with a small diameter with blue emission can
      be obtained. On the other hand, surface reconstruction barely has time to occur,
      and the surface is likely defect-ridden, which enables the existence of a broad
      emission covering the range of green, yellow and red regions. This is essential
      for the white light emission of CdS QDs, and is very important for WLED
      applications. The temporal evolution of the PL spectra for CdS QDs was obtained
      to investigate the influence of growth time on the luminescent properties. The
      CdS QDs with a growth time of 0.5 min exhibited a colour rendering index (CRI) of
      79.5 and a correlated colour temperature (CCT) of 6238 K. With increasing
      reaction time, the colour coordinates of the CdS QDs will move away from the
      white light region in the CIE 1931 chromaticity diagram. By integrating the as
      prepared white light emission CdS QDs with a violet GaN chip, WLEDs were
      fabricated. The fabricated WLEDs exhibited a CRI of 87.9 and a CCT of 4619 K,
      which satisfy the demand of general illumination. The luminous flux and the
      luminous efficiency of the fabricated WLEDs, being less advanced than current
      commercial white light sources, can be further improved, meaning there is a need
      for much more in-depth studies on white light emission CdS QDs.

PMID- 29469817
TI  - Novel optical assessments of tissue composition and viability using fluorescence
      spectroscopy and tissue oxygenation spectrophotometry in patients with systemic
      sclerosis: a pilot study.
AB  - OBJECTIVE: Patients with systemic sclerosis (SSc) experience significant
      morbidity and mortality, therefore, the development of tests to aid its early
      diagnosis are very important. The aim of this pilot study was to assess the
      diagnostic value of novel optical non-invasive skin fluorescence spectroscopy
      (FS) and tissue oxygen saturation (TOS) viability measurements in patients with
      established SSc. APPROACH: Two groups were studied, comprising 14 SSc patients
      and nine healthy controls (93% and 73% females, respectively). FS and TOS
      measurements were collected from three body sites: the forearm, chest, and calf.
      Fluorescence intensities at wavelengths attributed to collagen, elastin, and L
      tryptophan were computed, with adjustment for melanin, and a normalised combined
      fluorescence score (NCFS) was determined. MAIN RESULTS: The NCFS was
      significantly higher (p  <  0.001) and the combined TOS significantly lower (p  <
      0.001) in the SSc group. TOS measurements alone showed good classification
      accuracy (95.7%) at separating SSc from healthy control participants, with some
      clustering of values close to the 50% oxygenation level in both groups. When the
      composition and viability measures were combined and modelled using binary
      logistic regression, excellent results for the sample were obtained following
      leave one out cross validation (100%). SIGNIFICANCE: The results of this pilot
      study demonstrate the potential diagnostic utility of FS and TOS assessments in
      SSc patients and further work is now needed to validate these techniques
      prospectively in a larger group of SSc patients across the spectrum of the
      disease, and also patients with other types of vasculopathy and conditions that
      can cause skin fibrosis.

PMID- 29469818
TI  - Multi-band magnetotransport in exfoliated thin films of Cu x Bi2Se3.
AB  - We report magnetotransport studies in thin (<100 nm) exfoliated films of Cu x
      Bi2Se3 and we detect an unusual electronic transition at low temperatures. Bulk
      crystals show weak superconductivity with [Formula: see text] K and a possible
      electronic phase transition around 200 K. Following exfoliation,
      superconductivity is supressed and a strongly temperature dependent multi-band
      conductivity is observed for T  <  30 K. This transition between competing
      conducting channels may be enhanced due to the presence of electronic ordering,
      and could be affected by the presence of an effective internal stress due to Cu
      intercalation. By fitting to the weak antilocalisation conductivity correction at
      low magnetic fields we confirm that the low temperature regime maintains a
      quantum phase coherence length [Formula: see text] nm indicating the presence of
      topologically protected surface states.

PMID- 29469819
TI  - The Long Noncoding RNA HOTAIR in Breast Cancer: Does Autophagy Play a Role?
AB  - HOTAIR (HOX transcript antisense RNA) plays a critical role in chromatin dynamics
      through the interaction with histone modifiers resulting in transcriptional gene
      silencing. The promoter of the HOTAIR gene contains multiple estrogen response
      elements (EREs) and is transcriptionally activated by estradiol in estrogen
      receptor-positive breast cancer cells. HOTAIR competes with BRCA1, a critical
      protein in breast cancer and is a critical regulator of genes involved in
      epithelial-to-mesenchymal transition. It mediates an oncogenic action of c-Myc,
      essential for breast carcinogenesis. The carcinogenic action of HOTAIR was
      confirmed in breast cancer stem-like cells, in which it was essential for self
      renewal and proliferation. Several miRNAs regulate the expression of HOTAIR and
      HOTAIR interacts with many miRNAs to support cancer transformation. Many studies
      point at miR-34a as a major component of HOTAIR-miRNAs-cancer cross-talk. The
      most important role of HOTAIR can be attributed to cancer progression as its
      overexpression stimulates invasion and metastasis. HOTAIR can regulate autophagy,
      important for breast cancer cells survival, through the interaction with miRNAs
      specific for autophagy genes and directly with these genes. The role of HOTAIR
      mediated autophagy in breast cancer progression can be underlined by its
      interaction with matrix metalloproteinases, essential for cancer invasion, and
      beta-catenin can be important for this interaction. Therefore, there are several
      mechanisms of the interplay between HOTAIR and autophagy important for breast
      cancer, but further studies are needed to determine more details of this
      interplay.

PMID- 29469820
TI  - The Unexpected Tuners: Are LncRNAs Regulating Host Translation during Infections?
AB  - Pathogenic bacteria produce powerful virulent factors, such as pore-forming
      toxins, that promote their survival and cause serious damage to the host. Host
      cells reply to membrane stresses and ionic imbalance by modifying gene expression
      at the epigenetic, transcriptional and translational level, to recover from the
      toxin attack. The fact that the majority of the human transcriptome encodes for
      non-coding RNAs (ncRNAs) raises the question: do host cells deploy non-coding
      transcripts to rapidly control the most energy-consuming process in cells-i.e.,
      host translation-to counteract the infection? Here, we discuss the intriguing
      possibility that membrane-damaging toxins induce, in the host, the expression of
      toxin-specific long non-coding RNAs (lncRNAs), which act as sponges for other
      molecules, encoding small peptides or binding target mRNAs to depress their
      translation efficiency. Unravelling the function of host-produced lncRNAs upon
      bacterial infection or membrane damage requires an improved understanding of host
      lncRNA expression patterns, their association with polysomes and their function
      during this stress. This field of investigation holds a unique opportunity to
      reveal unpredicted scenarios and novel approaches to counteract antibiotic
      resistant infections.

PMID- 29469821
TI  - The Molecular Design of Active Sites in Nanoporous Materials for Sustainable
      Catalysis.
AB  - At the forefront of global development, the chemical industry is being confronted
      by a growing demand for products and services, but also the need to provide these
      in a manner that is sustainable in the long-term. In facing this challenge, the
      industry is being revolutionised by advances in catalysis that allow chemical
      transformations to be performed in a more efficient and economical manner. To
      this end, molecular design, facilitated by detailed theoretical and empirical
      studies, has played a pivotal role in creating highly-active and selective
      heterogeneous catalysts. In this review, the industrially-relevant Beckmann
      rearrangement is presented as an exemplar of how judicious characterisation and
      ab initio experiments can be used to understand and optimise nanoporous materials
      for sustainable catalysis.

PMID- 29469825
TI  - Performance analysis of an optical self-interference cancellation system with a
      directly modulated laser-based demonstration.
AB  - In this paper, two main performance indices of the optical self-interference
      cancellation (OSIC) system are theoretically analyzed: cancellation bandwidth and
      depth. Delay deviation is investigated to be the determining factor of
      cancellation bandwidth, based on which the bandwidth advantage of the OSIC system
      over electrical schemes is also proven theoretically. Cancellation depth in the
      narrowband is mostly influenced by attenuation and delay-adjusting deviation,
      while in the broadband case, the performance is mostly limited by frequency
      dependent amplitude and phase mismatch. The cancellation performance analysis is
      suitable for most linear modulation-demodulation OSIC systems, including the
      directly modulated laser (DML)-based OSIC system verified experimentally in this
      paper. The cancellation model is well demonstrated by the agreement between
      experimental cancellation results and predicted performance. For over-the-air
      demonstration with the employment of antennas, broadband cancellation within 450
      MHz bandwidth of 22 dB and 25 dB is achieved at 900 MHz and 2.4 GHz,
      respectively. In addition, orthogonal frequency division multiplexing signals are
      employed to show in-band full-duplex transmission with good performance by the
      DML-based OSIC system, with successful suppression of self-interference and
      recovery of the signal of interest.

PMID- 29469826
TI  - Er-doped Q-switched fiber laser with a black phosphorus/polymethyl methacrylate
      saturable absorber.
AB  - A stable Q-switched Er-doped fiber (EDF) laser is successfully obtained by using
      a black phosphorus (BP)/polymethyl methacrylate (PMMA) film as the saturable
      absorber (SA). To avoid the oxidization of nanomaterials, the BP nanoparticles
      are fabricated via a liquid-phase exfoliation method and then embedded into a
      PMMA film that possesses excellent optical transparency in the selected spectrum
      range. The modulation depth (MD) of the BP/PMMA film SA is 14.3% and the
      saturable intensity (Isat) is 6.9  MW/cm2. By inserting the BP/PMMA film into the
      EDF laser cavity, we achieve the stable passive Q-switching operation over the
      wavelength range from 1561.21 nm to 1564.16 nm. The repetition rate increases
      from 10.348 kHz to 30.098 kHz, and the pulse duration decreases from 25.01 MUs to
      2.98 MUs by altering the pump power from 9 mW to 90 mW. The maximum single pulse
      energy is 283.91 nJ. To the best of our knowledge, 283.91 nJ is the largest
      single pulse energy among the Q-switched fiber lasers with BP as the Q-switcher
      at the 1.5 MUm wavelength region. The experimental results evidently show that
      the BP/PMMA film SA can work as a promising Q-switcher for large pulse energy
      fiber lasers.

PMID- 29469822
TI  - Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants.
AB  - PURPOSE: To characterize the molecular genetics of autosomal recessive Noonan
      syndrome. METHODS: Families underwent phenotyping for features of Noonan syndrome
      in children and their parents. Two multiplex families underwent linkage analysis.
      Exome, genome, or multigene panel sequencing was used to identify variants. The
      molecular consequences of observed splice variants were evaluated by reverse
      transcription polymerase chain reaction. RESULTS: Twelve families with a total of
      23 affected children with features of Noonan syndrome were evaluated. The
      phenotypic range included mildly affected patients, but it was lethal in some,
      with cardiac disease and leukemia. All of the parents were unaffected. Linkage
      analysis using a recessive model supported a candidate region in chromosome
      22q11, which includes LZTR1, previously shown to harbor mutations in patients
      with Noonan syndrome inherited in a dominant pattern. Sequencing analyses of 21
      live-born patients and a stillbirth identified biallelic pathogenic variants in
      LZTR1, including putative loss-of-function, missense, and canonical and
      noncanonical splicing variants in the affected children, with heterozygous,
      clinically unaffected parents and heterozygous or normal genotypes in unaffected
      siblings. CONCLUSION: These clinical and genetic data confirm the existence of a
      form of Noonan syndrome that is inherited in an autosomal recessive pattern and
      identify biallelic mutations in LZTR1.

PMID- 29469827
TI  - Investigations on surface morphology and bandgap engineering of single crystal
      boron-doped silicon irradiated by a nanosecond laser.
AB  - We irradiate the single crystal boron-doped silicon (Si) at various laser
      fluences with 100 laser shots in ambient air at room temperature using an Nd:YAG
      laser and investigate its surface morphology and optical properties. The optical
      microscopy gives evidence of the formation of a crater and reveals that the heat
      affected zone and melted area are increased with increase in laser fluence from
      1.1 to 15.4  J/cm2. The micrographs obtained by scanning electron microscopy
      (SEM) show that the micro- and nano-structures such as microcracks, bubbles,
      nucleation sites, clusters, redeposited layered material, nanoparticles, and
      alike water droplet structures are formed on a laser-exposed Si surface. The
      optical profilometry of the irradiated Si further confirms the ablation and
      redeposition of the material and shows that the depth of the crater is increased
      from 12.1 to 15.2 MUm with increase in fluence from 1.1 to 15.4  J/cm2. Raman
      spectroscopy of the samples shows that the irradiation generates anneal effects
      due to higher temperature, which increases the crystallinity of the Si. The
      ellipsometric analysis shows that the irradiation of Si with increasing laser
      fluence changes its optical constants (refractive index and extinction
      coefficient), which further influence its optical properties, e.g., reflectivity,
      absorptivity, and energy bandgap. The absorptivity of laser irradiated Si tends
      to increase with increasing laser fluence, and the energy bandgap is decreased
      accordingly due to increase in structural disorders. Our study shows that the
      controlled laser irradiation can tune the energy bandgap of exposed Si, and it
      makes the Si materials useful for the fabrication of optoelectronic devices such
      as solar cells, photovoltaic cells, and LEDs.

PMID- 29469828
TI  - Non-contact XUV metrology of Ru/B4C multilayer optics by means of Hartmann
      wavefront analysis.
AB  - Short-wavelength imaging, spectroscopy, and lithography scale down the
      characteristic length-scale to nanometers. This poses tight constraints on the
      optics finishing tolerances, which is often difficult to characterize. Indeed,
      even a tiny surface defect degrades the reflectivity and spatial projection of
      such optics. In this study, we demonstrate experimentally that a Hartmann
      wavefront sensor for extreme ultraviolet (XUV) wavelengths is an effective non
      contact analytical method for inspecting the surface of multilayer optics. The
      experiment was carried out in a tabletop laboratory using a high-order harmonic
      generation as an XUV source. The wavefront sensor was used to measure the
      wavefront errors after the reflection of the XUV beam on a spherical Ru/B4C
      multilayer mirror, scanning a large surface of approximately 40 mm in diameter.
      The results showed that the technique detects the aberrations in the nanometer
      range.

PMID- 29469829
TI  - Measurement of multispecies concentration and gas temperature in an ammonium
      dinitramide-based thruster by tunable diode lasers.
AB  - In this paper, quantitative experiments were made to measure the concentration of
      key intermediate products (CO, N2O, and NO) and the gas temperature for
      combustion flow based on near-infrared and mid-infrared laser absorption
      spectroscopy. This paper used the developed diagnostic system to study two main
      ignition modes of a real 1-Newton thruster based on ammonium dinitramide (ADN):
      steady-state firing and pulse-mode firing over a feed pressure of 5-12 bar. The
      steady-state firing experiments distinguished the whole process into catalytic
      decomposition stage and combustion stage, experimentally demonstrating the
      combustion kinetics mechanism of an ADN monopropellant. Experiments for pulse
      mode firing showed the measured multispecies concentration and temperature were
      consistent with pulse trains, verifying good performance for the thruster pulse
      mode firing operation. The performance of the thruster was given based on the
      optical measurements, and characteristic velocity for the ADN-based thruster
      standard operation was higher than the corresponding 1-Newton hydrazine thruster.

PMID- 29469830
TI  - Space-inhomogeneous phase modulation of laser radiation in an electro-optical
      ferroelectric liquid crystal cell for suppressing speckle noise.
AB  - Spatially inhomogeneous modulation of a phase delay with the depth of the order
      pi or more makes it possible to destroy phase relations in a laser beam passing
      through an electro-optical cell with the ferroelectric liquid crystal (FLC) and,
      as a consequence, to suppress speckle noise in images formed by this beam. Such a
      modulation is a consequence of chaotic changes in the position of the scattering
      indicatrix of helix-free FLC, when an electro-optical cell is simultaneously
      supplied with a low-frequency and high-frequency bipolar control voltage. In this
      work, the phase modulation and effective suppressing of the speckles are realized
      using a new type of helix-free FLC material with periodic deformations of smectic
      layers.

PMID- 29469831
TI  - Wide color gamut display with white and emerald backlighting.
AB  - This paper proposes a wide color gamut approach that uses white and emerald
      lighting units as the backlight of the liquid crystal display. The white and
      emerald backlights are controlled by the image to be displayed. The mixing ratio
      of the white and the emerald lighting is analyzed so that the maximal color gamut
      coverage ratio can be achieved. Experimental results prove the effectiveness of
      the wide color gamut approach using white and emerald backlights.

PMID- 29469832
TI  - Upconversion luminescence of Ba3La(PO4)3:Yb3+-Er3+/Tm3+ phosphors for optimal
      temperature sensing.
AB  - To explore new upconversion (UC) luminescent materials for optical temperature
      sensing, a series of Ba3La1-x(PO4)3:0.1Yb3+,xEr3+ (abbreviated as BLP:0.1Yb3+,
      xEr3+, 0.01<=x<=0.03) and Ba3La1-y(PO4)3:0.1Yb3+,yTm3+ (abbreviated as
      BLP:0.1Yb3+, yTm3+, 0.005<=y<=0.015) phosphors was designed. For Yb3+-Er3+
      codoped BLP, the UC emission spectra exhibit a gradual enhancement with
      increasing pump power, and two-photon process for the green and red emissions of
      Er3+ has been confirmed by studying the dependence of UC emission intensities on
      excitation power. When the temperature rises, the fluorescence intensity ratio
      (FIR) for the H11/22-4I15/2 and S3/24-4I15/2 emissions of Er3+ increases
      gradually due to the thermalization of populations at the H11/22 and S3/24
      levels. With the temperature increased, the absolute sensitivity (SA) shows a
      continuous increase and reaches about 4.38*10-3  K-1 at 498 K, but the relative
      sensitivity (SR) decreases gradually. For Yb3+-Tm3+ codoped BLP, the emission
      intensity of Tm3+ shows a gradual decrease with increasing Tm3+ concentration. By
      studying the temperature dependence of FIR for the (F23,F33)-H63 and H43-3H6
      emissions, it has been found the sample exhibits a higher SR value but a lower SA
      value relative to the Yb3+-Er3+ codoped BLP.

PMID- 29469833
TI  - Acquisition technology for optical ground stations in satellite-ground quantum
      experiments.
AB  - To establish optical links between an optical ground station (OGS) and a quantum
      experiment satellite, a method of acquisition for the Micius satellite is
      proposed in this paper and the acquisition technological specification of the OGS
      system is analyzed. An acquisition strategy for the OGS is designed to meet the
      requirements of the quantum experiments. A method is designed to point accurately
      at the quantum satellite and improve the absolute pointing precision. The results
      show that the correction accuracy is better than 5 MUrad, the acquisition time is
      less than 5 s, and the acquisition probability is 100% so far.

PMID- 29469834
TI  - Near-infrared absorbers based on the heterostructures of two-dimensional
      materials.
AB  - Although the conductance and dielectric function of graphene can be tuned by
      applying external voltage, the tunability is less than 3%. Hybridizing graphene
      with other two-dimensional transition metal dichalcogenides (TMDs) can improve
      the adjustability and tunability of the optical properties of graphene-based
      structures at near-infrared frequencies. In this paper, we theoretically compute
      the dielectric function of graphene-MoTe2-graphene and graphene-MoTe2-graphene
      heterostructures utilizing the quantum electrostatic heterostructure (QEH) model,
      which is an ab-initio method. Utilizing the QEH results, we propose a hyper
      crystal (HC) absorber at near-infrared frequencies. Hence, we use the transfer
      matrix method to investigate our proposed absorber analytically. Moreover, we
      simulate the graphene-TMD-graphene (G-TMD-G) absorbers by the numerical finite
      difference time domain method. The results of the numerical solution are
      consistent with those of the analytical method. Due to the dependency of the
      Fermi level of graphene on the direct bandgap of the TMDs, the dielectric
      function of the G-TMD-G heterostructure can be tuned and enhanced further by
      changing the number of TMD layers. Finally, we demonstrate that the full
      absorption of the heterostructures can be achieved at different frequencies for
      transverse magnetic polarization. Since the thicknesses of the layers in the HC
      are lower than the wavelength of the light, no diffracted bands are ubiquitous,
      and the absorption can be observed for a wide range of incidence angles and
      bandwidths at near-infrared frequencies. Because of utilizing graphene-based HCs,
      in addition to the feasibility of design compared to the complex metasurfaces,
      the absorption bandwidth is significant for a wide range of incidence angles.
      This kind of HC absorber can be used in the design of sensitive optical devices,
      such as tunable filters, detectors, and photovoltaic applications.

PMID- 29469835
TI  - Design of a high-efficiency train headlamp with low power consumption using dual
      half-parabolic aluminized reflectors.
AB  - We propose a train headlamp system using dual half-circular parabolic aluminized
      reflectors. Each half-circular reflector contains five high-efficiency and small
      package light-emitting diode (LED) chips, and the halves are 180 degrees 
      rotationally symmetric. For traffic safety, the headlamp satisfies the Code of
      Federal Regulations. To predict the pattern of illumination, an analytical
      derivation is developed for the optical path of a ray that is perpendicular to
      and emitted from the center of an LED chip. This ray represents the main ray
      emitted from the LED chip and is located at the maximum illuminance of the spot
      projected by the LED source onto a screen. We then analyze the design
      systematically to determine the locations of the LED chips in the reflector that
      minimize electricity consumption while satisfying reliability constraints
      associated with traffic safety. Compared to a typical train headlamp system with
      an incandescent or halogen lamp needing several hundred watts, the proposed
      system only uses 20.18 W to achieve the luminous intensity requirements.

PMID- 29469836
TI  - Rapid super-resolution confocal microscopy through virtual structured detection
      based on serial scanning in array.
AB  - To improve the imaging speed of a confocal microscope with virtual structured
      detection, we have designed an optical system with rigid coordination control of
      the CCD, galvanometer scanner, and laser diode. In this system, the width of the
      coherent transfer function expands, which enhances the lateral resolution by a
      factor of 1.4. Also, the temporal image sequence is transformed to a spatial one
      so that multiple images can be acquired during a single exposure period of the
      CCD. This method increases the system imaging speed 25-fold at least, and an even
      higher speed can be achieved by further increasing the number of spots recorded
      during a single exposure period.

PMID- 29469837
TI  - Kayaking paddle blade compression load distribution sensing system based on
      optical fiber with a polydimethylsiloxane membrane.
AB  - This paper proposed a novel real-time compression load measurement system for a
      kayaking paddle based on optical fiber technology. The optical fiber sensor,
      fiber Bragg grating, is embedded in a 2 mm polydimethylsiloxane membrane, which
      serves as a pressure mat that can be easily attached/detached to/from the
      kayaking paddle. The proposed system is proposed for measuring and evaluating
      both handgrip loading and paddle blade load distribution during on-water
      kayaking, e.g., peak compression load distribution pattern and duration of the
      paddle blade in real time. Both indoor prototype experiment results and on-water
      experimental data on an expert paddler were presented to demonstrate the
      application potential of the proposed system.

PMID- 29469838
TI  - Laser fabrication of diffractive optical elements based on detour-phase computer
      generated holograms for two-dimensional Airy beams.
AB  - We have designed, fabricated, and tested an amplitude diffractive optical element
      for generation of two-dimensional (2D) Airy beams. The design is based on a
      detour-phase computer-generated hologram. Using laser ablation of metallic films,
      we obtained a 2  mm*2  mm diffractive optical element with a pixel of 5  MUm*5 
      MUm and demonstrated a fast, cheap, and reliable fabrication process. This device
      can modulate 2D Airy beams or it can be used as a UV lithography mask to
      fabricate a series of phase holograms for higher energy efficiency. Tests
      according to the premise and an analysis of the transverse profile and
      propagation are presented.

PMID- 29469839
TI  - High dynamic range 3D shape measurement based on the intensity response function
      of a camera.
AB  - Fringe projection profilometry has been widely used in many fields for its
      advantages such as high speed, high accuracy, and robustness to environmental
      illumination and surface texture. However, it is vulnerable to high dynamic range
      (HDR) objects. To this end, we propose a technique that can enhance the dynamic
      range of the fringe projection profilometry system. According to the surface
      reflectivities of the measured objects, several groups of fringe patterns with
      optimal light intensities are generated based on the intensity response function
      of a camera. The HDR fringe images are acquired by fusing these fringe patterns,
      and a three-step phase-shifting algorithm is used to obtain the unwrapped phase
      from the fused images. Experimental results demonstrate that the proposed
      technique can accurately measure objects with an HDR of surface reflectivity
      variation.

PMID- 29469840
TI  - Modeling of an interface between isorefractive media by a resistive surface.
AB  - In this study, the scattering of plane waves by a half-plane with different face
      impedances, which lie between isorefractive media, is analyzed. A new approach
      for the solution of this scenario is proposed. According to this proposal, the
      problem of isorefractive media and an impedance half-plane is modeled by a
      junction of resistive and impedance sheets. Thus the diffraction coefficient of
      the construction is obtained with the aid of the equivalent problem. The uniform
      expression of the diffracted waves is derived by the method of the uniform theory
      of diffraction. The scattered and diffracted waves are investigated numerically.

PMID- 29469841
TI  - Nonrotationally symmetric aberrations of off-axis two-mirror astronomical
      telescopes induced by axial misalignments.
AB  - In unobscured off-axis astronomical telescopes with an offset pupil, the effects
      of axial misalignments are very different from those in on-axis ones.
      Specifically, a series of nonrotationally symmetric aberrations with
      characteristic field dependence will be induced by axial misalignments. This
      paper takes off-axis two-mirror astronomical telescopes as an example to discuss
      the field characteristics of several important nonrotationally symmetric
      aberrations (including astigmatism, coma, and trefoil aberration) induced by
      axial misalignments in off-axis astronomical telescopes. The expressions of these
      aberrations are derived under some approximations. The accuracy of the proposed
      expressions is demonstrated. The specific field characteristics of these
      aberrations are presented and explicated. It is shown that the effects of axial
      misalignments bear strong similarities to the effects of the lateral
      misalignments in the symmetry plane of the off-axis system. On the other hand,
      the inherent relationships between astigmatism and coma induced by axial
      misalignments are further revealed, which are different from those induced by
      lateral misalignments. This fact presents the possibility of separating the
      effects of axial misalignments and lateral misalignments. Most of this work can
      be extended to other off-axis astronomical telescopes with more freedom.

PMID- 29469842
TI  - Aberration laser beams with autofocusing properties.
AB  - We investigate theoretically, numerically, and experimentally a novel type of
      laser beam-an aberration laser beam (ALB). To generate the ALB, a diffractive
      optical element with a phase transmission function having an arbitrary radial
      dependence of power q and a periodic angular dependence of sin(mphi) or cos(mphi)
      form can be used. Such a light distribution is more general than classic
      aberrations including Zernike polynomials. We demonstrate that such radial
      nonuniformity results in autofocusing properties of ALBs. The autofocusing
      feature of ALBs is analogous to that of circular Airy beams, but the ALBs'
      autofocusing feature has more flexibility. The presence of the periodic angular
      dependence in the phase results in a diffraction pattern with mth-order symmetry.
      Transformation of ALBs during propagation in free space is analogous to
      transformation of the three-Airy beams; however, the generated light
      distributions have an arbitrary integer order of symmetry. The presence of an
      additional focusing lens leads to formation of an optical field in its focal
      plane with symmetry that depends on the parity of m: for even m, the generated
      light distribution has 2mth-order symmetry, and, for odd m, it has mth-order
      symmetry.

PMID- 29469843
TI  - Investigation of the interpolation method to improve the distributed strain
      measurement accuracy in optical frequency domain reflectometry systems.
AB  - We use a spectrum interpolation technique to improve the distributed strain
      measurement accuracy in a Rayleigh-scatter-based optical frequency domain
      reflectometry sensing system. We demonstrate that strain accuracy is not limited
      by the "uncertainty principle" that exists in the time-frequency analysis.
      Different interpolation methods are investigated and used to improve the accuracy
      of peak position of the cross-correlation and, therefore, improve the accuracy of
      the strain. Interpolation implemented by padding zeros on one side of the
      windowed data in the spatial domain, before the inverse fast Fourier transform,
      is found to have the best accuracy. Using this method, the strain accuracy and
      resolution are both improved without decreasing the spatial resolution. The
      strain of 3 MUepsilon within the spatial resolution of 1 cm at the position of
      21.4 m is distinguished, and the measurement uncertainty is 3.3 MUepsilon.

PMID- 29469844
TI  - Second-harmonic-generation-based technique for examining laser diode wavelength
      dynamics in the MUs to ms range.
AB  - Wavelength information is essential for any researcher in optics and photonics,
      and for this reason, a wide range of devices is available for measuring it.
      However, the techniques available today are limited either to a resolution of
      nanometers or a measurement rate of kHz. In this paper, we present a simple but
      highly versatile technique based on second-harmonic generation to measure fast
      wavelength dynamics of laser diodes. We demonstrate a resolution of 0.7 pm and a
      measurement rate in the MHz range. The measurement rate is limited only by the
      photodetector, and the wavelength resolution is limited mainly by the length of
      the nonlinear crystal and the noise of the detectors. The technique can, e.g., be
      used to investigate the mode-hop behavior of laser diodes during pulsed
      operation. To demonstrate this, we show the wavelength changes of a laser diode
      during a single pulse.

PMID- 29469845
TI  - Inverse design of optical elements based on arrays of dielectric spheres.
AB  - Arrays of wavelength scale scatterers are a promising platform for designing
      optical elements with a compact footprint. The large number of degrees of freedom
      in this system allows for unique and plentiful functionalities. However, the many
      variables also create a complex design problem. While intuitive forward design
      methods work for simple optical elements, they often fail to produce complicated
      elements, especially those involving multiple elements. We present an inverse
      design methodology for large arrays of wavelength scale spheres based on both
      adjoint optimization or sensitivity analysis and generalized multi-sphere Mie
      theory as a solution to the design problem. We validate our methodology by
      designing two sets of optical elements with scatterers on sub-wavelength and
      super-wavelength periodic grids. Both sets consist of a singlet and a doublet
      lens with one and two layers of spheres respectively designed for 1550 nm. The
      designed NA is ~0.33 (~0.5) for the sub-wavelength (super-wavelength) periodic
      structure. We find that with the sub-wavelength periodicity, the full width at
      half-maximum of the focal spot produced by the singlet and doublet is smaller
      than that produced by an ideal lens with the same geometric parameters. Finally,
      we simulate a realistic experimental scenario for the doublet, where the spheres
      are placed on a substrate with the same refractive index. We find the performance
      is similar, but with lower intensity at the focal spot and larger spot size. The
      method described here will simplify the design procedure for complicated multi
      functional optical elements and or scatterer array-based volume optics based on a
      specified figure of merit.

PMID- 29469846
TI  - Dual-view integral imaging three-dimensional display using polarized glasses.
AB  - We propose a dual-view integral imaging (DVII) three-dimensional (3D) display
      using polarized glasses. The DVII 3D display consists of a display panel, a
      polarized parallax barrier, a microlens array, and two pairs of polarized
      glasses. Two kinds of elemental images, which are captured from two different 3D
      scenes, are alternately arranged on the display panel. The polarized parallax
      barrier is attached to the display panel and composed of two kinds of units that
      are also alternately arranged. The polarization directions between adjacent units
      are perpendicular. The polarization directions of the two pairs of polarized
      glasses are the same as those of the two kinds of units of the polarized parallax
      barrier, respectively. The lights emitted from the two kinds of elemental images
      are modulated by the corresponding polarizer units and microlenses, respectively.
      Two different 3D images are reconstructed in the viewing zone and separated by
      using two pairs of polarized glasses. A prototype of the DVII 3D display is
      developed and two 3D images can be presented simultaneously, verifying the
      hypothesis.

PMID- 29469847
TI  - Doppler-free spectroscopy of metastable Sr atoms using a hollow cathode lamp.
AB  - We report on the demonstration of Doppler-free spectroscopy of metastable Sr
      atoms using a hollow cathode lamp (HCL). We employed a custom Sr HCL, which is
      filled with a mixture of 0.5 Torr Ne and 0.5 Torr Xe as a buffer gas to suppress
      velocity changing collisions and increase the populations in all of the
      (5s5p)3PJ(J=0,1,2) metastable states. We performed frequency modulation
      spectroscopy for the (5s5p)3P0-(5s6s)3S1, (5s5p)3P1-(5s6s)3S1, (5s5p)3P2
      (5s5d)3D2, and (5s5p)3P2-(5s5d)3D3 transitions with sufficient signal-to-noise
      ratios for laser frequency stabilization. We also observed the hyperfine
      transitions of (5s5p)3P2-(5s5d)3D3 of Sr87. This method would greatly facilitate
      laser cooling of Sr.

PMID- 29469848
TI  - Comparison of imaging fiber bundles for coherence-domain imaging.
AB  - Use of imaging fiber bundles for coherence-domain imaging has remained limited to
      date. In this work, we provide characterization of commercially available imaging
      bundles for coherence-domain imaging, by evaluating their modal structure for
      applicability to interferometric imaging. We further examine custom fabricated
      bundles developed in collaboration with a corporate partner for their ability to
      reduce interelement optical path length variability and cross talk between
      elements. The results presented here will serve as a useful guide for comparing
      fiber bundles for coherence imaging while also offering an improved understanding
      of the functionality and limitations of imaging bundles for advancing coherent
      imaging technologies.

PMID- 29469849
TI  - Highly thermal-stable heterodyne interferometer with minimized periodic
      nonlinearity.
AB  - Heterodyne interferometers suffer from thermal drift of optics (TDO), which may
      introduce error even up to several micrometers. In this paper, we propose a
      symmetric heterodyne interferometer with spatially separated beams, which
      realizes completely balanced optical paths between probe and reference beams and
      simultaneously avoids the optical mixing, and thereby is theoretically capable of
      eliminating TDO and the periodic nonlinearity (PNL). To validate the performance
      of the proposed interferometer, first a special experimental setup is
      constructed, with which the TDO test can be conducted in vacuum, and the result
      shows that a thermal coefficient of 1.2 nm/ degrees C is achieved. Next, the PNL
      of the proposed interferometer is measured by both the frequency domain method
      and the phase quadrature method, which demonstrates an undetectable PNL at a
      noise level of 13 pm.

PMID- 29469850
TI  - Watt-level tunable narrow bandwidth Tm:YAP laser using a pair of etalons.
AB  - We demonstrated in this paper a watt-level tunable, narrow band, end-pumped
      Tm:YAP laser. Spectral tunability of 35 nm ranging continuously between 1917-1951
      nm with a spectral linewidth of 0.15 nm FWHM was achieved. The tuning and
      spectral band narrowing were obtained using a pair of YAG etalons. Watt-level
      output power was measured along the laser tunable range, obtaining a maximal
      output power of 3.88 W at 1934 nm. A slope efficiency of 44.8% is demonstrated
      for a maximal absorbed pump power of 12.1 W. The combination of the narrow
      bandwidth with tunability at those output power levels makes this laser a
      promising tool for biomedical, sensing, and material processing applications.

PMID- 29469851
TI  - Desensitization design method of unobscured three-mirror anastigmatic optical
      systems with an adjustment-optimization-evaluation process.
AB  - An off-axis three-mirror anastigmatic optical system with the offset apertures
      configuration as a typical unobscured optical system is frequently used in
      various optical instruments. The practical applications show that this type of
      system has a higher sensitivity in alignment. To reduce the alignment sensitivity
      of the unobscured optical systems, a desensitization design method with an
      adjustment-optimization-evaluation process is proposed. By ray path difference
      analysis based on the optical system mathematical models, the mirror off-axis
      magnitude value is determined as a significant factor influencing system
      alignment sensitivity. Accordingly, in the desensitization design process, the
      mirror off-axis magnitude value is set as an adjustment, and the image quality
      and system sensitivity are set as the criteria. By a design example, it proves
      that the desensitization design method is effective and practical, and the design
      result sensitivity analysis not only verifies that the off-axis magnitude is a
      significant factor that influences the system alignment sensitivity, but also
      finds that there is a positive correlation relation between system sensitivity
      and off-axis magnitude value. The desensitization method can design the
      unobscured optical systems with less alignment sensitivity and robust tolerance.

PMID- 29469853
TI  - Improvement of Scheimpflug systems with freeform surfaces.
AB  - It is well known that freeform surfaces are used to improve the resolution in
      systems without rotational symmetry. For Scheimpflug systems, the tilted object
      plane leads to variant magnification in the system imaging. Thus, the system
      suffers from non-rotationally symmetric aberrations, non-uniform resolution, and
      non-uniform intensity distribution. In this paper, the paraxial imaging condition
      of Scheimpflug systems is discussed. From the classical viewpoint, the aberration
      theory is used to understand, balance, and improve the system performance for
      variant object distance. For large object distance shift, it is necessary to
      apply freeform surfaces. With the initial system design method based on Gaussian
      brackets, the starting configuration of a Scheimpflug system with large object
      distance shift is obtained. Based on the extension of the Nodal aberration theory
      concerning the aberrations of freeform surfaces, the rules of selecting the
      freeform surface position in the system are introduced. By adding two freeform
      surfaces far away from the pupil, the aberrations are effectively corrected in
      the Scheimpflug system. The aberrations along the field are decomposed and
      represented using Zernike fringe polynomials to show the improvement of
      uniformity and resolution. This work provides insight into Scheimpflug system
      design with freeform surfaces.

PMID- 29469852
TI  - Air wedge with variable refractive index for precise laser beam steering in a
      small range.
AB  - This paper provides the results of work on a new method for metrological laser
      beam steering for the purpose of angular stabilization. Frequency stabilized
      metrological lasers are used for interference measurements of length and angle.
      Angular deviation of the beam may cause cosine errors when measuring
      displacements. This paper presents a method for metrological laser beam
      deflection with an air wedge of variable refractive index. The change in the
      index is achieved by changing the air pressure in the wedge volume. The
      implemented system produced a range of angular displacements of the 0.1 mrad (10
      4  rad; 100 MUrad) beam with a resolution of 10-7  rad.

PMID- 29469854
TI  - All-fiber polarization-maintaining erbium-doped dispersion-managed fiber laser
      based on a nonlinear amplifying loop mirror.
AB  - In this paper, we build a mode-locked all-polarization-maintaining figure-of-8
      erbium-doped fiber oscillator based on a nonlinear amplifying loop mirror. The
      fiber oscillator can generate 1.6 ps chirped pulses that can be de-chirped to 500
      fs at 1550 nm with a pulse energy of 0.8 nJ and a repetition rate of 12 MHz. It
      can be further amplified up to 10 nJ and compressed down to 100 fs with a pre
      chirp managed nonlinear amplification setup. Such an oscillator and amplifier
      configuration has the advantages of self-starting and long-term operation, and it
      is highly suitable for subsequent frequency conversion, which is desirable for
      many applications in ultrafast microscopy and precision spectroscopy.

PMID- 29469855
TI  - High-energy diode side-pumped Er:LiYF4 laser.
AB  - This work presents a novel diode side-pumping scheme for Er:YLF with a
      characteristic laser emission at 2.81 MUm. Average output powers greater than 10
      W and corresponding pulse energies exceeding 100 mJ with a high slope efficiency
      of 18.7% are achieved. The Er:YLF laser efficiently operates at room-temperature
      cooling water and maintains a good beam quality of M2<12 in the major axis and
      M2<6 in the minor axis of the beam profile. The laser cavity is studied by means
      of Findlay-Clay analysis, and the operation at characteristic pump parameters is
      investigated. In addition, a dynamic laser rate equation simulation is introduced
      for quantitative and qualitative comparison. This compact and scalable free
      running Er:YLF laser provides an effective building block for a subsequent Q
      switching concept.

PMID- 29469856
TI  - Spatially incoherent common-path off-axis color digital holography.
AB  - We describe a new method for recording spatially incoherent common-path off-axis
      color digital holograms. We present the theoretical and experimental evidence to
      demonstrate an incoherent common-path off-axis color digital holographic (ICOCH)
      system capable of capturing information from three-dimensional color objects
      under incoherent illumination, both in transmission and reflection modes. Fresnel
      incoherent correlation holography (FINCH), a common-path system, is a frequently
      used incoherent holography technique. Our proposed system is conceptually similar
      to an advanced form of FINCH; moreover, it has three advantages over this
      advanced form of FINCH. First, removal of the spatial light modulator makes our
      system simpler and more cost-effective. Second, removal of the polarizer or
      analyzer allows for greater light throughput. Third, the off-axis optical
      configuration enables separation of zero-order and twin images with only a single
      exposure per color rather than requiring three exposures per color for in-line
      holography FINCH. Therefore, we believe that this simple and cost-effective
      system with high light throughput can acquire incoherent holograms for different
      colors involving single exposure for each color, which makes the ICOCH system
      suitable for many applications.

PMID- 29469857
TI  - Design of a gradient-index lens with a compound parabolic concentrator shape as a
      visible light communication receiving antenna.
AB  - We propose a design for a gradient lens that can extend the field of view and
      receive higher optical power for indoor visible light communication systems. The
      proposed structure is an axially symmetric lens with a refractive index gradient
      distribution in the axial direction and a slight gradient in the radial
      direction, and with a spherical top surface and side surface in a compound
      parabolic concentrator (CPC) shape. The radius of the outlet of the CPC is 3 mm,
      and the inlet radius is 6.8 mm with a 9.04 mm radius of curvature. The height of
      the receiving system is 15.2 mm, resulting in the small volume of the structure.
      Simulation results show that the half field of view (FOV) of the lens can reach
      36.2 degrees , while the gain is higher than that of a bare CPC. The designed
      receiving system has an average receiving gain ~1.72 times larger than a bare CPC
      based system, and is suitable for indoor visible light communication.

PMID- 29469858
TI  - High-performance color sequence particle streak velocimetry for 3D airflow
      measurement.
AB  - In this paper, a high-performance color sequence particle streak velocimetry
      (CSPSV) technique is proposed to measure the air velocity in a large three
      dimensional (3D) space. Based on the basic principle of CSPSV, a new color
      sequence illumination pattern is designed to mark seeding bubbles for better
      imaging performance. Synchronized with the illumination system, cameras record
      the targets' paths at the start, middle, and end points with different color
      information more clearly. Thus, a rectification-based stereo corresponding
      algorithm is presented to reconstruct the 3D trajectory of the bubbles. The
      accuracy of this system is verified and shows good consistency with a hot-wire
      anemometer (the principal research tool for turbulent-flow studies). The vortex
      test experiments also indicate its capability for complex airflow. Our high
      performance CSPSV can extend the 3D measurement zone from several cubic
      centimeters to several cubic meters with regular, off-the-shelf cameras.

PMID- 29469859
TI  - "Achromatic limits" of Pancharatnam phase lenses.
AB  - Lenses based on the Pancharatnam phase have the advantage of being thin and
      inexpensive. Unfortunately, their optical effect is strongly wavelength
      dependent, and their applications generally are limited by the requirement of a
      monochromatic source. However, low-power lenses based on the Pancharatnam phase
      can be considered for applications over the visible range. In this paper, we
      provide intuitive "limits" for the lens power, below which these devices can be
      considered for use with the eye and visible light imaging applications.

PMID- 29469860
TI  - Symmetric decomposition of experimental depolarizing Mueller matrices in the
      degenerate case.
AB  - We propose a detailed procedure to determine the two retardance matrix factors
      entering the symmetric decomposition of Mueller matrices when the depolarizer
      matrix is partially degenerate (i.e., two out of three of its depolarization
      coefficients are equal), which is a common occurrence. Thanks to a relatively
      simple algebraic method, we show that linear retardance, as well as its eigenaxes
      orientation can be determined unambiguously from each retardance matrix factor.
      The method, applied on both experimental Mueller matrices of an ad hoc sample, as
      well as on that of a biological tissue, shows its efficiency for decoupling the
      different polarimetric effects of retardance that occur during the propagation of
      light throughout a complex medium.

PMID- 29469861
TI  - Five-step phase-shifting white-light interferometry for the measurement of fiber
      optic extrinsic Fabry-Perot interferometers.
AB  - Five-step phase-shifting white-light interferometry is presented for
      interrogating the absolute cavity length of the fiber optic extrinsic Fabry-Perot
      interferometer (EFPI). It combines ideas of phase-shifting interferometry and
      white-light interferometry (WLI) to extend the measurement range of fiber optic
      WLI. Five sub-interferograms intercepted from the white-light optical spectrum
      are used to recover the optical path difference (OPD) of the EFPI. This method is
      demonstrated to interrogate a wider range of OPD. The experimental results show
      that the measurement resolution ranges from 0.5 MUm to 5 MUm with cavity length
      ranges from 16 MUm to 12,402 MUm, and it has a great advantage in measuring EFPIs
      with short cavity lengths.

PMID- 29469862
TI  - Tunable spectral and spatial filters for the mid-infrared based on hyperbolic
      metamaterials.
AB  - In this paper we present the possibility of shaping the reflectivity
      characteristics of tunable hyperbolic metamaterials (THMMs). Using the example of
      voltage-sensitive graphene-based structures, we demonstrate the existence of
      spectral and spatial functionalities of edge and narrowband filters, controlled
      dynamically over a 3-5 MUm spectral range, that are important for both civilian
      and military applications. We also demonstrate that the adoption of apodization
      techniques in the THMM design leads to a reduction in the sidelobe's parasitic
      effect in edge filters, as well as providing the means to reshape the overall
      reflectivity characteristics, which not only unveiled the tunable angle aperture
      functionality but also significantly increased the potential for tailoring
      optical properties of THMM nanostructures in general.

PMID- 29469863
TI  - Scattering characteristics of a cylindrical reflector covered with a general bi
      isotropic layer.
AB  - The scattering characteristics of an electric line source radiating in the
      presence of a bi-isotropic coated circular cylindrical reflector have been
      investigated using numerical calculations. The analytic expressions of the
      electric and magnetic fields in the bi-isotropic coating and the background
      medium have been found using the wave-field decomposition approach. It is studied
      that a bi-isotropic coating enhances the gain in the forward direction as
      compared to chiral, Tellegen, and dielectric coatings. It is found that for a
      thin coating layer, the scattering gains in the forward direction for chiral and
      bi-isotropic coatings are almost the same. It is investigated that a specific
      type of bi-isotropic coating can be used to significantly enhance the scattering
      gain in the forward direction. This type of enhanced forward direction scattering
      gain is preferred in point to point communications. On the other hand, it is
      found that a specific type of Tellegen coating significantly reduces the
      scattering gain in the backward direction. This phenomenon of reduced gain can be
      used to hide a cylindrical reflector in the backward direction. A comparative
      study of the scattering gains for realistic bi-isotropic and low-loss dielectric
      coatings has also been discussed.

PMID- 29469864
TI  - Computer-generated hologram marked by correlated photon imaging.
AB  - The computer-generated hologram (CGH) has been studied for many applications. In
      this paper, CGH is watermarked by correlated photon imaging. An input image is
      encoded into two cascaded phase-only masks by using the CGH principle.
      Subsequently, two different marks are independently encoded into one-dimensional
      (1D) intensity points by using correlated photon imaging (or ghost imaging), and
      the recorded 1D intensity points are embedded into the extracted phase masks for
      optical watermarking. During the decoding, the input is recovered by using two
      watermarked phase masks. To verify copyright of the recovered input image,
      information embedded in two phase-only masks is retrieved and used to decode the
      hidden marks. The decoded marks do not visually render clear information due to
      only a few measurements and, instead, are authenticated. It is illustrated that
      the quality of the recovered input image is high, and a different imaging
      approach can be applied in the CGH system for optical watermarking. The proposed
      approach provides a promising strategy for optical information security.

PMID- 29469865
TI  - Cost-effective plane-grating monochromator design for extreme-ultraviolet
      application.
AB  - The optical design of a plane-grating monochromator mainly intended for high
      resolution in the extreme ultraviolet and soft x-ray is presented. The
      configuration has three optical elements. It uses a uniform line-spaced plane
      grating illuminated in the converging light coming from a focusing concave mirror
      and an additional plane mirror that is needed to change the grating subtended
      angle to keep the system in focus on a fixed slit. The parameters of the focusing
      mirror are determined to introduce a coma that compensates for the coma given by
      the grating. A monochromator for the 12-50 eV region is designed for application
      to high-order laser harmonics.

PMID- 29469866
TI  - Design of an optical trap for storing femtosecond laser pulses.
AB  - An optical trap for storing femtosecond laser pulses to enhance the interaction
      effectiveness with optically thin targets is being proposed and investigated.
      Presently, we studied the trapping of 10-200 fs laser pulses of wavelength 800
      nm, 1 MUJ energy per pulse, and 10 Hz repetition rate. To compensate the optical
      losses in the trap, a Ti: Sapphire crystal as an amplifying medium is being
      considered, which should be synchronously pumped by the second harmonic of the
      Nd: YAG laser. Due to the propagation of the short pulses through optical trap
      components, group velocity dispersion introduces a significant broadening in
      pulse duration. To compensate for this broadening, a chirped mirror with suitable
      parameters is being proposed. An increase of the average power of the laser pulse
      in the optical trap that includes an amplifying medium (Ti: Sapphire crystal) by
      a factor of 805 compared to a single passage of the laser pulse was derived. It
      should be possible to store the laser pulse in the optical trap for >4  MUs with
      constant power and with a repetition rate of up to 250 MHz.

PMID- 29469867
TI  - Freeform lens design to eliminate retroreflection for optical systems.
AB  - This paper presents an effective approach to alleviate the cat-eye effect by
      inserting a freeform single lens into the original optical system. By shifting
      the image of the given optical system transversely on the original image plane,
      the reflected beams originating from the sensor are subsequently blocked by the
      optical aperture, substantially eliminating retroreflections from the system. The
      influence of incident angle on retroreflected beams is analyzed in detail, and
      the optimal image translation distance for completely eliminating the cat-eye
      effect is also proposed via numerical simulations. According to the translation
      requirement, a freeform single lens comprised of two different freeform surfaces
      is designed for the given system as the only translation element. The design
      recipe is elaborated on the basis of phase pupil function. Furthermore, a design
      example is demonstrated to verify the feasibility of our proposal. After
      optimization with optical design software, the modulation transfer function (MTF)
      of the modified system after translation is close to the diffraction limit, and
      the cat-eye reflected beam could be eliminated thoroughly.

PMID- 29469868
TI  - Diverse mode of operation of an all-normal-dispersion mode-locked fiber laser
      employing two nonlinear loop mirrors.
AB  - In this paper, we propose an all-normal-dispersion ytterbium-fiber laser with a
      novel ring cavity architecture having two nonlinear amplifying loop mirrors
      (NALM) as saturable absorbers, capable of delivering distinctly different pulses
      with adjustable features. By optimizing the loop lengths of the individual NALMs,
      the cavity can be operated to deliver Q-switched mode-locked (Q-ML) pulse bunches
      with adjustable repetition rates, mode-locked pulses in dissipative soliton
      resonance (DSR) regime or noise-like pulse (NLP) regime with tunable pulse width.
      The DSR pulses exhibit characteristic narrowband spectrum, while the NLPs exhibit
      large broadband spectrum. The operation regime of the laser can be controlled by
      adjusting the amplifier pump powers and the polarization controllers. To the best
      of the authors' knowledge, this is the first demonstration of a single mode
      locked cavity where narrowband DSR pulses and broadband NLPs alongside Q-ML pulse
      bunches can be selectively generated by employing two NALMs.

PMID- 29469869
TI  - Nondestructive evaluation of demineralized enamel in a human incisor and molar
      using laser ultrasonics.
AB  - This study aims to evaluate early caries in human teeth with different geometry
      structures by using the dispersion curves of a surface acoustic wave (SAW)
      generated by a pulsed laser. Through the finite element method, SAWs propagating
      on teeth models with different enamel thickness and curvature radius were
      simulated, and the influence of the geometry difference on the dispersion curves
      of SAWs was discussed. Laser ultrasonic experiments were performed on an
      extracted human incisor and molar with different demineralization conditions. The
      received dispersive surface wave signals were processed via the spectral analysis
      method to obtain the dispersion curves, and the difference of the dispersion
      spectra between the incisor and the molar was analyzed and discussed. The result
      demonstrates that the laser generating the SAW has the ability to evaluate the
      elastic properties of early caries with different geometry nondestructively.

PMID- 29469870
TI  - Real-time identification of the singleness of a trapped bead in optical tweezers.
AB  - Beads trapped in optical tweezers are aligned along the optical propagation
      direction, which makes it difficult to determine the number of beads with bright
      field microscopy. This problem also dramatically influences the measurement of
      the optical trapping based single-molecule force spectroscopy. Here, we propose a
      video processing approach to count the number of trapped micro-objects in real
      time. The approach uses a normalized cross-correlation algorithm and image
      enhancement techniques to amplify a slight change of the image induced by the
      entry of an exotic object. As tested, this method introduces a ~10% change per
      bead to the image similarity, and up to four beads, one-by-one falling into the
      trap, are identified. Moreover, the feasibility of the above analysis in a moving
      trap is investigated. A movement of the trap leads to a fluctuation of less than
      2% for the similarity signal and can be ignored in most cases. The experimental
      results prove that image similarity measurement is a sensitive way to monitor the
      interruption, which is very useful, especially during experiments. In addition,
      the approach is easy to apply to an existing optical tweezers system.

PMID- 29469871
TI  - Comb-referenced frequency-sweeping interferometry for precisely measuring large
      stepped structures.
AB  - A precise 3D surface measurement method for large stepped structures without
      height ambiguity is proposed based on optical-frequency-comb-referenced frequency
      sweeping interferometry and Fourier-transformed fractional phase retrieval.
      Unlike other interferometry that depends on the absolute phase value for several
      certain wavelengths, this method obtains results from the phase change during
      frequency sweeping and thus remains free from the confined non-ambiguity range.
      By reference to an optical frequency comb, the relative uncertainty from the
      tunable laser frequency was reduced by three orders of magnitude, and the
      sweeping frequency range can be precisely determined. Besides, the fractional
      phase can be rapidly retrieved in only one step using a Fourier transform method,
      with advantages of high accuracy and immunity to light intensity fluctuation and
      mechanical vibration noise. Samples of step heights from 1 MUm to 1 mm were
      measured, and the standard uncertainty was 45 nm. This permits applications such
      as quality assurance in microelectronics production and micro-electro-mechanical
      system (MEMS) manufacture.

PMID- 29469872
TI  - Compact optical multipass matrix system design based on slicer mirrors.
AB  - High path-to-volume ratio (PVR) and low-aberration-output beams are the two main
      criteria to assess the performance of multipass absorption cells. However, no
      substantial progress has been reported for large-numerical-aperture-coupled
      multipass cells, which is due to the accumulated aberrations caused by a large
      number of off-axis reflections. Based on Chernin's design, in this study, we
      modified Chernin's four-objective multipass matrix cell by using slicer mirrors
      to eliminate alignment difficulty and decrease the system volume. A generalized
      design routine based on user requirements is also proposed. Based on the
      automatic modeling tool package (Pyzdde) connected with Zemax and boundary
      conditions of the parameters selection proposed, a low-aberration-output beam and
      a high PVR are easily obtained compared with other multipass cells schemes. In
      one demo design, 108 passes (5*7 matrix spots) in a base length of 300 mm are
      presented. The PVR and peak-to-valley value wavefront errors are 67.5 m/L and
      0.92 MUm, respectively. Finally, a tolerance analysis of this optical multipass
      system is also presented. This work may provide better broadband optical
      absorption cells in terms of response time and a better detection sensitivity in
      versatile applications.

PMID- 29469873
TI  - Calculation model of the scattering polarization coherency matrix for a detection
      system of oil spills at sea.
AB  - As a new analytical method to identify oil spills at sea, the main effect of a
      polarization measurement system is the scattering polarization information of
      different measured parts. To improve measurement accuracy, the scattering
      polarization characteristics of oil film and seawater were observed in this
      paper. A useful computational model, the scattering polarization coherency matrix
      (SPCM), was derived, which is a probabilistic mixture of the polarization
      coherency matrix. Combined with the Fresnel formula, the amplitude ratio and
      phase retardation were extracted to verify the scientific nature of the physical
      model. Experiments were performed, and the SPCM of the oil film and seawater were
      measured. In order to test the practicability of the model, we derived the degree
      of polarization from the SPCM and used it as the basis for identification of the
      actual oil spill at sea in the case of sunlight. Research indicated that the path
      of multiple scattering was in connection with the molecular structure and
      interactions of the medium. Under different measuring angles, the SPCM of the oil
      film and seawater have both differences and regularities; the experimental
      results indicate that it can be used for the rapid detection of an oil spill at
      sea, and the data are accurate and reliable.

PMID- 29469874
TI  - Temperature-dependent optical constants of highly transparent solids determined
      by the combined double optical pathlength transmission-ellipsometry method.
AB  - The optical constants of five highly transparent substrates (polycrystalline
      BaF2, CaF2, MgF2, ZnSe, and ZnS) were experimentally determined based on a
      combined technique using both the double optical pathlength transmission method
      and the ellipsometry method within temperature range 20 degrees C-350 degrees C
      in the ultraviolet-infrared region (0.2-20 MUm). The results show that the
      refractive index spectra of polycrystalline BaF2, CaF2, and MgF2 are similar, but
      differ from that of polycrystalline ZnSe and ZnS. The thermo-optic coefficient of
      these highly transparent substrates increases with increasing temperature. The
      absorption indices show a significant temperature-dependent behavior, which
      increases with increasing temperature from 20 degrees C to 350 degrees C over the
      transparent region. For the sake of application, the fitted formulas of the
      refractive index of the five highly transparent substrates as a function of
      wavelength and temperature are presented.

PMID- 29469875
TI  - Quantitative detection of oxygen in reduced graphene oxide by femtosecond laser
      induced breakdown spectroscopy.
AB  - This paper proposes a simple, direct, and fast method for the quantitative
      detection of oxygen in reduced graphene oxide (r-GO) by femtosecond laser-induced
      breakdown spectroscopy (fs-LIBS). First, GO was reduced by continuous-wave (CW)
      laser beams with different powers; subsequently, the oxygen content in the r-GO
      was detected through the intensity of oxygen obtained by fs-LIBS. The fit of the
      observed data and errors by LIBS was compared with the results of x-ray
      photoelectron spectroscopy (XPS), and the fs-LIBS results correlate well with the
      XPS results; it indicated that fs-LIBS can realize quantitative analysis of the
      GO-reduction degree. The method provides a convenient and time-efficient way for
      detecting the reduction degree of r-GO and can extend the applications of r-GO
      with different reduction degrees.

PMID- 29469876
TI  - Visible Infrared Imaging Radiometer Suite reflective solar bands on-orbit
      calibration using solar diffuser illuminated by scattered light through the nadir
      port.
AB  - A new variant to the standard on-orbit calibration of the reflective solar bands
      (RSBs) using a solar diffuser (SD) is formulated. Instead of direct solar
      exposure through the SD port in the front of the instrument as originally
      designed, the variant method uses light reflecting off Earth's surface coming
      through the nadir port as the light source to illuminate the built-in onboard SD.
      The methodology is applied to the Visible Infrared Imaging Radiometer Suite on
      board the Suomi National Polar-orbiting Partnership satellite, and is shown to be
      viable and useful. This approach effectively preserves the standard calibration
      pipeline other than using a different set of illumination data, corresponding to
      a different illumination source, for computing the radiance emanating from the
      SD. It has the added advantages of not dealing with operational needs for the
      standard calibration activities and completely bypassing the characterization of
      the transmission function of the attenuation screen in the front of the SD port.
      The RSB calibration coefficients are computed from the data of scattered light
      from the SD sector per each orbit, and a 16-day average is taken. The variant
      calibration coefficients are shown to well match the standard solar-based RSB
      calibration coefficients for Bands M5 to M8, but diverging results emerge for
      Bands M1 to M4, highlighting the known non-ideal behavior in the degradation of
      SD that contributes to the worsening error in RSB calibration. The result also
      shows a consistent 2% variation mission-long for all RSBs, showing the overall
      consistency of this first analysis of the new method but also the level of the
      uncertainty. The result and the implications of this study are discussed.

PMID- 29469877
TI  - Q-plates with a nonlinear azimuthal distribution of the principal axis:
      application to encoding binary data.
AB  - We encode q-plates where the angular orientation of the principal axis is varied
      spatially with a nonstandard distribution. In the usual q-plate design, the
      orientation of the optical axis depends linearly on the azimuthal angle. In this
      work, we examine cases where this azimuthal dependence is nonlinear. We consider
      two cases: first, where the principal axis distribution is like an inverse
      tangent function of the azimuth; and second, where it displays linear and flat
      segments. This last case is proposed as a new method for encoding binary data
      into the azimuthal lobes of the vector beam. We encode these patterns using a
      spatial light modulator system that allows new and exotic q-plate designs without
      the difficulty of fabricating individual plates. Experimental results are
      presented.

PMID- 29469878
TI  - Design and analysis of a triple reflection grazing incidence x-ray telescope.
AB  - A triple reflection grazing incidence x-ray telescope is proposed and evaluated.
      This form of an optical system can detect x-ray energy that is close to the
      optical axis, which solves the problems encountered by traditional Wolter-type
      systems. In this paper, we also propose a new design method to ensure that the
      entire telescope structure is compact and integrated. Finally, a proof-of-concept
      design with an acceptable image quality is proposed.

PMID- 29469879
TI  - Light-absorbing aerosol properties retrieved from the sunphotometer observation
      over the Yangtze River Delta, China.
AB  - In this study, aerosol optical depth (AOD) and extinction Angstrom exponent (EAE)
      are derived from ground-based sunphotometer observations between 2007 and 2014 at
      urban sites of Nanjing over the Yangtze River Delta. In addition, the present
      study aims to investigate aerosol light-absorbing properties such as single
      scattering albedo (SSA), absorption Angstrom exponent (AAE), and the aerosol
      absorbing optical depth (AAOD). The retrieval of aerosol properties is compared
      with AERONET inversion products. The results demonstrate that the retrieved AOD
      has a good agreement with the AERONET Level 1.5 data, with the root mean square
      error being 0.068, 0.065, and 0.026 for total, fine mode, and coarse mode at 440
      nm, respectively. The SSA values indicate similar accuracies in the results,
      which are about 0.003, -0.009, -0.008, and 0.010 different from AERONET at 440,
      670, 870, and 1020 nm, respectively. The occurrence frequency of background level
      AOD (AOD<0.10) at 440 nm in this region is limited (1%). Monthly mean AOD, SSA,
      the effective radius (Reff), and the volume concentration at 440 nm were 0.6-1.3,
      0.85-0.92, 0.24-0.40 MUm, and 0.18-0.28  MUm3 MUm-2, respectively. The mean value
      of AAOD at 440 nm (AAOD440) was the highest in both summer (0.095+/-0.041) and
      autumn (0.094+/-0.042), but was the lowest in winter (0.079+/-0.036). It was also
      noted that SSA was found to be higher during summer (0.89+/-0.05). The spectral
      variation of SSA was observed to be strongly wavelength-dependent during all
      seasons. The seasonal mean AAE440-870 is the highest in winter (0.86+/-0.41) and
      lowest in spring (0.49+/-0.29). In winter, the cumulative frequency for AAE
      between 1.0 and 1.2 was about 87%. The peak in the AAE distribution was close to
      1.0, indicating that the aerosol column was dominated by urban-industrial
      aerosols and absorption species other than black carbon. Analysis of the
      relationship between EAE and SSA showed that the aerosol populations could be
      classified as "mixed" aerosol, including a mixture of both anthropogenic
      particles and secondary organic aerosol with highly variable sphericity fraction.

PMID- 29469880
TI  - Calibration of the degree of linear polarization measurements of the polarized
      Sun-sky radiometer based on the POLBOX system.
AB  - Polarization observation of sky radiation is the frontier approach to improve the
      remote sensing of atmospheric components, e.g., aerosol and clouds. The
      polarization calibration of the ground-based Sun-sky radiometer is the basis for
      obtaining accurate degree of linear polarization (DOLP) measurement. In this
      paper, a DOLP calibration method based on a laboratory polarized light source
      (POLBOX) is introduced in detail. Combined with the CE318-DP Sun-sky polarized
      radiometer, a calibration scheme for DOLP measurement is established for the
      spectral range of 440-1640 nm. Based on the calibration results of the Sun-sky
      radiometer observation network, the polarization calibration coefficient and the
      DOLP calibration residual are analyzed statistically. The results show that the
      DOLP residual of the calibration scheme is about 0.0012, and thus it can be
      estimated that the final DOLP calibration accuracy of this method is about 0.005.
      Finally, it is verified that the accuracy of the calibration results is in
      accordance with the expected results by comparing the simulated DOLP with the
      vector radiative transfer calculations.

PMID- 29469881
TI  - Accurate estimation of the illumination pattern's orientation and wavelength in
      sinusoidal structured illumination microscopy.
AB  - Structured illumination microscopy is able to improve the spatial resolution of
      wide-field fluorescence imaging by applying sinusoidal stripe pattern
      illumination to the sample. The corresponding computational image reconstruction
      requires precise knowledge of the pattern's parameters, which are its phase (phi)
      and wave vector (p). Here, a computationally inexpensive method for estimation of
      p from the raw data is proposed and illustrated with simulations. The method
      estimates p through a selective discrete Fourier transform at tunable subpixel
      precision. This results in an accurate p estimation for all the illumination
      patterns and subsequently improves the superresolution image recovery by a factor
      of 10 around sharp edges as compared to an integer pixel approach. The technique
      as presented here is of major interest to the large variety of custom-build
      systems that are used. The feasibility of the presented method is proven in
      comparison with published data.

PMID- 29469882
TI  - Microlens array expander with an improved light intensity distribution
      throughperiodic submicro-scale filling for near-eye displays.
AB  - A type of microlens array (MLA) expander with an improved light intensity
      distribution (LID) is designed and fabricated through submicro-scale filling,
      which could be applied to near-eye displays. Through the reflection of a 0.8-MUm
      wide metal filling, the light field is split and superimposed only through the
      microlens. The bright spot at the center of the LID is effectively eliminated.
      The results demonstrate that the expanded numerical aperture (NA) and focal
      length are about 0.38 and 19 MUm, respectively, and the error in the radius of
      curvature is within 5% between the experimental and designed values. An improved
      image quality with an 80% brightness uniformity for an area of 22*22  mm2 is
      realized through the MLA. Compared with the MLA based on thermal reflow, the
      largest NA is obtained with the smallest focal length and gap. The experimental
      LID is consistent with that obtained by a theoretical simulation.

PMID- 29469883
TI  - Focus detection by shearing interference of vortex beams for non-imaging systems.
AB  - In focus detection of non-imaging systems, the common image-based methods are not
      available. Also, interference techniques are seldom used because only the degree
      with hardly any direction of defocus can be derived from the fringe spacing. In
      this paper, we propose a vortex-beam-based shearing interference system to do
      focus detection for a focused laser direct-writing system, where a vortex beam is
      already involved. Both simulated and experimental results show that fork-like
      features are added in the interference patterns due to the existence of an
      optical vortex, which makes it possible to distinguish the degree and direction
      of defocus simultaneously. The theoretical fringe spacing and resolution of this
      method are derived. A resolution of 0.79 MUm can be achieved under the
      experimental combination of parameters, and it can be further improved with the
      help of the image processing algorithm and closed-loop controlling in the future.
      Finally, the influence of incomplete collimation and the wedge angle of the shear
      plate is discussed. This focus detection approach is extremely appropriate for
      those non-imaging systems containing one or more focused vortex beams.

PMID- 29469884
TI  - Principal frequency component analysis based on modulate chopper technique used
      in diffuse reflectance spectroscopy measurement.
AB  - Diffuse reflectance spectroscopy (DRS) is significantly affected from the
      interference of the ambient light and dark current of the instrument. Optical
      choppers, together with lock-in/synchronous amplification, can overcome these
      interferences. However, in spectral measurement, the sampling rate of the
      spectrometer is different from the Delta-pulse sampling, which is not high enough
      because of the integration time. In addition, the energy distribution is not
      perfectly concentrated as expected in modulate chopper technology. Therefore, in
      this study, based on the modulate chopper technique, we proposed a principal
      frequency component analysis (PFCA) method for DRS. This technique not only
      effectively eliminated the interference and dark current of the instrument but
      also improved the measurement precision using the energy of different
      frequencies. First, experiments were designed to successfully verify the function
      of optical choppers, eliminating the interference of the ambient light. Second, a
      set of 64 mixture solutions was designed and measured by DRS using the PFCA
      method to prove the feasibility of the proposed method. The solution was mixed
      with intralipid-20% suspension, India ink, and rhodamine B. These samples were
      analyzed by DRS under different conditions: no-chopper with overlapping and
      averaging, chopper demodulated by Fourier transform, and chopper demodulated by
      PFCA. The partial least square regression analysis was implemented to predict the
      concentration. Compared to the result of three methods, DRS equipped with chopper
      using the PFCA method showed the best results. The results of this study showed
      that the PFCA method not only satisfactorily eliminated the interference signals
      but also extracted useful information as much as possible, improving the analysis
      accuracy.

PMID- 29469886
TI  - Study on the inversion of doped concentration induced by millisecond pulsed laser
      irradiation silicon-based avalanche photodiode.
AB  - In this paper, an experimental study of silicon-based avalanche photodiode (Si
      APD) with millisecond pulse laser irradiation was carried out, and the C-V curve
      of Si-APD was obtained by using a semiconductor analyzer. Based on the single
      side abrupt junction character of n+p, combined with the corresponding
      theoretical derivation, the doping concentration varying with the axial depth of
      damaged Si-APD was obtained by inverse computation. The lattice dislocation and
      junction reduction were the fundamental causes of the reduced doping
      concentration. The research results provide a new method for the study of the
      internal doping concentration for detectors with millisecond pulse laser damage.

PMID- 29469887
TI  - Orbital angular momentum channel monitoring of coaxially multiplexed vortices by
      diffraction pattern analysis.
AB  - We theoretically and experimentally demonstrate a scheme to monitor the weight of
      a single orbital angular momentum (OAM) channel for coaxial multiplexed optical
      vortices with large mode spacing. A specially designed holographic grating is
      illuminated by the incident multiplexed vortices first. Then the weight of each
      single OAM channel is obtained after analyzing the captured diffraction patterns.
      This work will find applications in domains where multiplexed optical vortices
      are of interest, such as the OAM-based data-transmission system, and so on.

PMID- 29469888
TI  - Compact optical fiber temperature sensor with high sensitivity based on liquid
      filled silica capillary tube.
AB  - We propose a highly sensitive fiber temperature sensor based on a section of
      liquid-sealed silica capillary tube inserted in a single-multi-single-mode fiber
      structure. The liquid polymer is filled into the silica capillary tube through
      two micro-holes drilled by a femtosecond laser. Then the micro-holes are blocked
      by UV curable adhesive with ultra-small volume. Obvious Mach-Zehnder interference
      peaks were shown in its transmission spectrum. The proposed fiber temperature
      sensor can be reliably used for actual point detection owing to its high
      sensitivity (8.09 nm/ degrees C), good linearity (99.93%), compact size, good
      mechanical property, high fabrication efficiency, and good repeatability and
      stability.

PMID- 29469890
TI  - Temporal coherence study of four-wave mixing products with and without the laser
      cavity effect.
AB  - In this work, we have studied the temporal coherence property of a four-wave
      mixing (FWM)-assisted continuous-wave erbium-doped fiber ring laser source. To
      understand the temporal coherence characteristics of FWM, we have analyzed the
      visibility of their interference pattern with the help of a Mach-Zehnder-based
      fiber interferometer. The visibility of FWM sidebands is compared with respect to
      the input pumps, with and without the cavity effect. The stand-alone FWM without
      any cavity effect has a visibility comparable to its input coherent pumps, while
      the FWM in the presence of the cavity effect has a poorer visibility due to the
      intra-cavity noise arising from the amplified spontaneous emission, which is not
      entirely annulled in broadband lasers. The study also confirms that the
      visibility/temporal coherence property of FWM sidebands does not depend on the
      efficiency of their generation.

PMID- 29469889
TI  - Optimized star sensors laboratory calibration method using a regularization
      neural network.
AB  - High-precision ground calibration is essential to ensure the performance of star
      sensors. However, the complex distortion and multi-error coupling have brought
      great difficulties to traditional calibration methods, especially for large field
      of view (FOV) star sensors. Although increasing the complexity of models is an
      effective way to improve the calibration accuracy, it significantly increases the
      demand for calibration data. In order to achieve high-precision calibration of
      star sensors with large FOV, a novel laboratory calibration method based on a
      regularization neural network is proposed. A multi-layer structure neural network
      is designed to represent the mapping of the star vector and the corresponding
      star point coordinate directly. To ensure the generalization performance of the
      network, regularization strategies are incorporated into the net structure and
      the training algorithm. Simulation and experiment results demonstrate that the
      proposed method can achieve high precision with less calibration data and without
      any other priori information. Compared with traditional methods, the calibration
      error of the star sensor decreased by about 30%. The proposed method can satisfy
      the precision requirement for large FOV star sensors.

PMID- 29469891
TI  - Effect of angle-of-arrival fluctuation on heterodyne detection in slant
      atmospheric turbulence.
AB  - A mathematical model of the effect of random pointing errors on the mixing
      efficiency of heterodyne detection is established, and the effect of angle-of
      arrival fluctuation on the mixing efficiency of heterodyne detection is
      investigated. The results show that the average mixing efficiency is
      significantly affected by the angle-of-arrival fluctuation in the outer scale.
      The larger the obscuration ratio and receiving aperture of the optical system,
      the lower the average mixing efficiency is. The closer the value of D/r0 is to
      0.79, the closer the bit error rate of heterodyne detection is to 1*10-9 under
      weak turbulence.

PMID- 29469892
TI  - Adjustable-focus ultracompact endoscopic lens design with ultrahigh optical
      performance.
AB  - An internally focusing design is developed for a compact endoscopic lens to have
      optical performance close to the diffraction limit. When changing the working
      distance from infinity to a predetermined short distance, the overall system
      length and the field of view remain constant. It is numerically demonstrated that
      the diffraction-limit-like performance is maintained over a wide range of working
      distances, showing a novel capability of adjustable focuses. The design concept
      is numerically proven to be feasible and can enable very high-resolution
      examination for doctors checking the positions of biological entities through the
      immediate capture of clear images at different working distances. The
      corresponding lens configuration, PNN, is shown to be useful in achieving the
      high-resolution performance once the number of lens elements is four, where P and
      N are used to denote positive and negative optical power, respectively, for the
      lens groups. A corresponding tolerance analysis is also presented.

PMID- 29469895
TI  - Highly amplified light transmission in a parity-time symmetric multilayered
      structure.
AB  - We propose a parity-time symmetric dielectric-nano-film-dielectric multilayered
      structure that could facilitate highly amplified transmission of optical power in
      the infrared spectrum. We have theoretically studied our model using the transfer
      matrix formalism. The reflection and the transmission coefficients of the S
      matrix are evaluated. The theoretical results are validated by FDTD numerical
      simulation. We have shown how the thickness of the layers and the gain/loss
      coefficient of the active layers could generate spectral singularities in the S
      matrix and how these singularities could be exploited to achieve amplified
      transmission of a single wavelength through the structure.

PMID- 29469894
TI  - Radiometric model for coaxial single- and multimode optical emission from double
      clad fiber.
AB  - Double-clad fibers (DCFs) are versatile waveguides supporting a single-mode core
      surrounded by a multimode inner cladding. DCFs are increasingly used for
      multimodal biomedical applications, such as imaging or therapy, for which the
      core is typically used for coherent illumination and the inner cladding, to
      support a concurrent modality. Proper optimization is, however, critical to
      ensure high optical performance and requires accurate modeling of coaxial single-
      and multimode output beams. In this paper, we present an approach based on
      geometrical optics and radiometry, which provides a simple and efficient modeling
      tool for designing and optimizing DCF-based systems. A radiometric definition of
      single- and multimode output beams in terms of irradiance and radiant intensity
      allows for the modeling of the energy distribution along the beams' propagation.
      We confirmed the validity of the model through comparison with experimental
      measurements and demonstrate the use of the model for optimizing a catheter for
      concurrent OCT and laser coagulation.

PMID- 29469897
TI  - Temperature-insensitive sum frequency generation of 355-nm ultraviolet laser
      radiation in LiB3O5 by compensating thermally induced phase mismatch.
AB  - A temperature-insensitive sum frequency generation method based on thermally
      induced phase mismatch compensation is proposed to enhance the thermal stability
      and scale up the output power of ultraviolet (UV) lasers. In the method, three
      LiB3O5 crystals are cascaded for sum frequency generation of a 355-nm UV laser,
      and the two crystals at the ends are employed for frequency conversion; the
      middle one, which is not required to be phase matched and has an opposite sign of
      first temperature derivative of phase mismatch, compensates the thermally induced
      phase mismatch generated in the first crystal. The temperature acceptance
      bandwidth of frequency conversion in the three cascaded crystals is about double
      that in a single long crystal with the same interaction length.

PMID- 29469885
TI  - Sixth-order wave aberration theory of ultrawide-angle optical systems: erratum.
AB  - In this erratum, two errors in our recently published paper [Appl. Opt.56, 8570
      (2017)APOPAI0003-693510.1364/AO.56.008570] are corrected.

PMID- 29469893
TI  - Weighted spline based integration for reconstruction of freeform wavefront.
AB  - In the present work, a spline-based integration technique for the reconstruction
      of a freeform wavefront from the slope data has been implemented. The slope data
      of a freeform surface contain noise due to their machining process and that
      introduces reconstruction error. We have proposed a weighted cubic spline based
      least square integration method (WCSLI) for the faithful reconstruction of a
      wavefront from noisy slope data. In the proposed method, the measured slope data
      are fitted into a piecewise polynomial. The fitted coefficients are determined by
      using a smoothing cubic spline fitting method. The smoothing parameter locally
      assigns relative weight to the fitted slope data. The fitted slope data are then
      integrated using the standard least squares technique to reconstruct the freeform
      wavefront. Simulation studies show the improved result using the proposed
      technique as compared to the existing cubic spline-based integration (CSLI) and
      the Southwell methods. The proposed reconstruction method has been experimentally
      implemented to a subaperture stitching-based measurement of a freeform wavefront
      using a scanning Shack-Hartmann sensor. The boundary artifacts are minimal in
      WCSLI which improves the subaperture stitching accuracy and demonstrates an
      improved Shack-Hartmann sensor for freeform metrology application.

PMID- 29469898
TI  - Distribution of splice loss in single mode optical fiber.
AB  - This work investigates a probabilistic model for splice loss in single mode
      optical fibers. We derive the probability density function for loss values as a
      function of lateral and angular misalignment. We then use observed data to
      estimate these model parameters; both Bayesian and maximum likelihood estimation
      procedures are described. These estimates can then be used to provide an
      indication of the relative importance of various loss mechanisms. Alternatively,
      if one is given values for maximum lateral and angular misalignment, our results
      allow for predictions of expected distribution of loss values. An overall goal of
      this paper is to demonstrate that, beyond the mean and variance of splice loss,
      there is significant information in the shape of the distribution of values. A
      second goal is to understand the trade-off between the number of splice loss
      measurements and the confidence in estimates of parameters in the splice loss
      model.

PMID- 29469896
TI  - Wavefront reconstruction of a non-coaxial diffraction model in a lens system.
AB  - To reconstruct a wavefront in a non-coaxial lens system, we propose a diffraction
      model using the Fresnel integral. Inclination angle is the newly included
      parameter in the mathematical formula describing beam propagation. It is
      determined through two ways in this paper, which are correlation operation and
      optical flow method. Furthermore, the multi-image phase retrieval is incorporated
      to reconstruct the complex optical field of sample from an overdetermined
      dataset. The combination is much closer to the actual situation and thus more
      practical. The proposed diffraction model is validated by numerical analysis and
      experiment. The work will further benefit the application of multi-image phase
      retrieval, such as in biomedical imaging and optical metrology.

PMID- 29469899
TI  - Commentary: Programmable base editing of A.T to G.C in genomic DNA without DNA
      cleavage.

PMID- 29469900
TI  - What Factors Lead to the Success of a Continuity Clinic Immersion Experience for
      Residents?

PMID- 29469901
TI  - Expression of miR-711 and mechanism of proliferation and apoptosis in human
      gastric carcinoma.
AB  - [This retracts the article DOI: 10.3892/ol.2017.6777.].

PMID- 29469902
TI  - Erratum: Stent retriever thrombectomy combined with local thrombolytic therapy
      for cerebral venous sinus thrombosis: A case report.
AB  - [This corrects the article DOI: 10.3892/etm.2017.5043.].

PMID- 29469903
TI  - Prevalence and pattern of cardiovascular risk factors in a population in India.
AB  - Background: Cardiovascular disease is the leading cause of mortality in India.
      Since it is largely driven by risk factors such as hypertension, diabetes and
      smoking, it is important to study the treatment cascade for these conditions and
      identify areas for improvement. Methods: This is a cross-sectional study from
      Project SEHAT (Study to Enhance Heart Associated Treatments), an ongoing cluster
      randomised controlled trial testing the hypothesis that a community health worker
      led intervention can improve the control of cardiovascular risk factors in a
      community in West Bengal, India. For the baseline data, 3556 adults, between the
      ages of 35 and 70, were screened for hypertension, diabetes and smoking. For
      hypertension and diabetes, an elevated reading was confirmed on a repeat visit.
      Results: 18.3% (n=650), 9.0% (n=317) and 14.1% (n=500) of adults were diagnosed
      with hypertension, diabetes and smoking, respectively. Overall, 35.0% (n=1242)
      adults had at least one of the three risk factors. 55.1% (n=358) of participants
      with hypertension and 40.4% (n=128) of participants with diabetes were unaware of
      their respective condition. 36.6% (n=238) of those with hypertension and 58.0%
      (n=184) of diabetics were on treatment. 8.2% (n=53) hypertensives were controlled
      (blood pressure <140/90 mm Hg) while 13.6% (n=43) diabetics were controlled
      (defined as fasting blood sugar <126 mg/dL). Less than 1% diabetics were on
      insulin, and average number of medications for a patient with hypertension was
      1.2. Conclusions: In our population in semiurban India, one in three adults have
      a major cardiovascular risk factor, with low control rates. There is a large
      burden of undiagnosed cardiovascular risk factors and a large gap between
      treatment and control, which may be explained by lack of treatment
      intensification.

PMID- 29469904
TI  - A Resident's Perspective on Academic Bullsh*t.

PMID- 29469906
TI  - Correction to: in-transit development of color abnormalities in turkey breast
      meat during winter season.
AB  - [This corrects the article DOI: 10.1186/s40781-017-0157-1.].

PMID- 29469905
TI  - Predictors of cardiac benefits of renal artery stenting from a multicentre
      retrospective registry.
AB  - Objectives: There have been limited data regarding the prediction of cardiac
      benefits after renal artery stenting for patients with atherosclerotic renal
      artery disease (ARAD). The aim of this multicentre retrospective study was to
      identify clinical or echocardiographic factors associated with improvements of
      cardiac symptoms after renal artery stenting. Methods: We enrolled 58 patients
      with de novo ARAD undergoing successful renal artery stenting for heart failure,
      angina or both between January 2000 and August 2015 at 13 hospitals. Results:
      Improvement of cardiac symptoms was observed in 86.2% of patients during a mean
      follow-up of 6.0+/-2.7 months. Responders demonstrated significantly lower New
      York Heart Association functional class, higher estimated glomerular filtration
      rate, lower serum creatinine and lower interventricular septal wall thickness
      (IVS), lower left ventricular mass index, lower left atrial dimension and lower E
      velocity than non-responders. Backward stepwise multivariate analysis identified
      IVS as an independent predictor of improvement of cardiac symptoms (OR 0.451, 95%
      CI 0.209 to 0.976; p=0.043). According to receiver operating characteristic curve
      analysis, an IVS cut-off of 11.9 mm provided the best predictive value, with
      sensitivity of 71.4%, specificity of 75.5% and accuracy of 73.5%. The positive
      predictive value was 74.5% and the negative predictive value was 72.5%.
      Conclusions: This multicentre retrospective study shows that the
      echocardiographic index of IVS is an independent predictor for improvement of
      cardiac symptoms after renal artery stenting.

PMID- 29469908
TI  - Limited Jaw Movements and Somatization (But Not Pain) May Play a Role in Salivary
      Flow in Female Patients with Temporomandibular Disorders.
AB  - AIMS: To explore the unstimulated salivary flow rate and subjective feeling of
      oral dryness in young adult women with temporomandibular disorders (TMD) and
      their relation to the presence of chronic pain, depression, somatization, and
      limited mandibular mobility. METHODS: Unstimulated whole saliva flow rate and
      presence of oral dryness were determined in 45 women with TMD and 30 healthy
      controls. The Research Diagnostic Criteria for TMD (RDC/TMD) were used for
      assessment of TMD, chronic pain, depression, somatization, and mandibular
      mobility. Factors with P < .05 in the bivariate analysis were included in
      multivariate modeling. RESULTS: The TMD patients showed significantly diminished
      unstimulated salivary flow (P = .010) in comparison to controls, but there was no
      difference in subjective oral dryness. Within the TMD group, patients with
      mandibular hypomobility and free from somatization exhibited significantly lower
      salivary output (P = .037; P = .015, respectively). No relationship between
      salivary flow and depression or TMD pain was observed. Multivariate linear
      regression identified somatization as the single variable contributing to
      salivary flow (P = .044) in the TMD patients. CONCLUSION: The present study shows
      a relationship between TMD and lower salivary flow but no evidence of a
      relationship between TMD and subjective oral dryness in young adult women.
      Somatization was the single variable to emerge from the evaluation of potential
      factors contributing to salivary output in TMD patients.

PMID- 29469907
TI  - Trend in prevalence of coronary artery disease and risk factors over two decades
      in rural Punjab.
AB  - Objectives: The burden of coronary artery disease (CAD) has increased in the last
      three decades in low-income and middle-income countries including India. CAD is
      responsible for 20% deaths in India. The burden of CAD has increased due to a
      higher prevalence of risk factors related to the changing lifestyle. We studied
      the change in prevalence of CAD and risk factors over 20 years in a rural area.
      Methods: A rural population of adults over the age of 30 years from three
      villages of Punjab was surveyed for the prevalence of CAD and its risk factors in
      1994 and 2014 using similar research methodology. CAD was diagnosed by Epstein
      and clinical criteria. Blood pressure, anthropometry, ECG and biochemical
      analysis were carried out. The findings of two surveys were compared with a look
      at the change in the prevalence of CAD and its risk factors over 20 years.
      Results: The overall age standardised prevalence of CAD increased from 2.79% in
      1994 to 4.06% (p<0.05) in 2014. There was a significant increase in the
      prevalence of several risk factors including sedentary lifestyle (8.2% vs 41.3%,
      p<0.001), hypertension (14.5% vs 26.5%, p<0.001), diabetes (4.7% vs 9.7%,
      p<0.001), obesity (16.6% vs 35.4, p<0.001) and hypercholesterolaemia (7% vs 9.6%,
      p 0.011). In contrast, cigarette smoking (8.9% vs 3%, p<0.001) and use of desi
      ghee (51.4% vs 28.5%, p<0.001) decreased. Conclusions: In a rural population of
      Punjab, the prevalence of several CAD risk factors like sedentary lifestyle,
      hypertension, diabetes, obesity and hypercholesterolaemia increased over 20
      years. These changes in risk factors were associated with a modest increase in
      prevalence of CAD.

PMID- 29469909
TI  - Composition-driven shape evolution to Cu-rich PtCu octahedral alloy nanocrystals
      as superior bifunctional catalysts for methanol oxidation and oxygen reduction
      reaction.
AB  - Synergetic effects between Pt and a cheap metal, downshift of the d-band center
      of Pt and the shape can boost the catalytic performance of Pt-based nanocrystals.
      Therefore, tailoring the shape and composition within the nanoscale is the key to
      designing a robust electrocatalyst in electrochemical energy conversion. Here, Cu
      rich PtCu octahedral alloys achieved by a composition-driven shape evolution
      route have been used as outstanding bifunctional electrocatalysts for both
      methanol oxidation (MOR) and oxygen reduction reaction (ORR) in an acid medium.
      When benchmarked against commercial Pt black or Pt/C, for MOR, the specific
      activity/mass activity on Pt34.5Cu65.5 octahedra is 4.74/7.53 times higher than
      that on commercial Pt black; for ORR, the specific activity/mass activity on
      Pt34.5Cu65.5 octahedra is 7.7/4.2 times higher than that on commercial Pt/C.
      After a current-time test for 3600 s, the remaining mass activity on Pt34.5Cu65.5
      octahedra is 35.5 times higher than that on commercial Pt black for MOR. After
      undergoing 5000 cycles for ORR, the remaining mass activity on Pt34.5Cu65.5
      octahedra is 4.2 times higher than that on commercial Pt/C.

PMID- 29469910
TI  - Preparation of acetals from aldehydes and alcohols under basic conditions.
AB  - A new, simple protocol for the synthesis of acetals under basic conditions from
      non-enolizable aldehydes and alcohols has been reported. Such reactivity is
      facilitated by a sodium alkoxide along with a corresponding trifluoroacetate
      ester, utilizing formation of sodium trifluoroacetate as a driving force for
      acetal formation. The usefulness of this protocol is demonstrated by its
      orthogonality with various acid-sensitive protecting groups and by good
      compatibility with functional groups, delivering synthetically useful acetals
      complementarily to the synthesis under acidic conditions from aldehydes and
      alcohols.

PMID- 29469911
TI  - New chiral amino alcohol ligands for catalytic enantioselective addition of
      diethylzincs to aldehydes.
AB  - A study aimed at the synthesis and structure optimization of new, efficient,
      optically active beta-amino alcohol ligands with a structure suitable for
      immobilization on magnetite nanoparticles has been carried out. The optimized
      homogeneous amino alcohol catalysts 13a and 13b, the chirality of which arises
      from the Sharpless epoxidation of suitable allyl alcohols, were tested by
      employing the well-established enantioselective amino alcohol-promoted addition
      of diethylzinc to benzaldehyde, giving the corresponding benzyl alcohol with
      nearly quantitative yield and ee = 95%. Then, their broad applicability as chiral
      catalysts was evaluated by carrying out the same reaction on a family of
      aldehydes, including variously substituted aromatic ones as well as an aliphatic
      analogue. The results have confirmed the validity of the fine-tuning process
      performed on ligands 13a and 13b. In fact, both exhibited excellent catalytic
      activity as demonstrated by the chemical yields and ee obtained from all the
      tested aldehydes, almost independent of the position and type of substitution in
      the aromatic ring.

PMID- 29469912
TI  - Towards energy efficient separations with metal organic frameworks.
AB  - The huge energy requirement for industrial separations of chemical mixtures has
      necessitated the need for the development of energy efficient and alternative
      separation techniques in order to mitigate the negative environmental impacts
      associated with greenhouse gas emissions from fossil fuel combustions for energy
      generation. A promising approach involves the use of magnetic framework
      composites (MFCs) for gas capture and release via localised magnetic induction
      heating in a process known as magnetic induction swing adsorption (MISA). This
      feature article presents an overview of the mechanism of induction heating of
      magnetic nanoparticles, incorporation of the nanoparticles into metal organic
      frameworks to form MFCs and the potential of deploying MFCs for the mitigation of
      greenhouse gas emissions using the MISA process. We also present an overview of
      the potential energy savings as a result of the efficiency of magnetic induction
      heating and we give a perspective on the future directions in material and
      process development that could lead to widespread deployment of the MISA process
      for industrial separation operations.

PMID- 29469913
TI  - Revisiting the carrageenan controversy: do we really understand the digestive
      fate and safety of carrageenan in our foods?
AB  - Carrageenan (CGN), a family of marine polysaccharides isolated from seaweeds, has
      been at the heart of considerable debate in recent years. To date, CGN is
      generally recognized as safe based on a history of safe use, various acute
      toxicology studies and some recent chronic toxicology tests. This review offers
      readers an overview of evidence on CGN characteristics and digestive fate that
      highlight various gaps in our understanding. Specifically, three unresolved gaps
      are identified. Firstly, little information can be found on the current levels of
      public exposure to CGN. Secondly, the link between CGN physicochemical
      properties, its impact on digestive proteolysis, the colon microbiome and
      inflammation are yet to be fully resolved. Thirdly, scant scientific evidence
      exists on the differential digestive fate of CGN in the gut of liable and
      predisposed populations, such as elderly people or IBD patients. Altogether,
      revisiting the scientific evidence indicates that more research is needed to
      elucidate the possibility that continued exposure to increasing levels of CGN in
      the human diet may compromise human health and well-being.

PMID- 29469914
TI  - Citrate stabilized gold nanoparticles interfere with amyloid fibril formation:
      D76N and DeltaN6 beta2-microglobulin variants.
AB  - Protein aggregation including the formation of dimers and multimers in solution,
      underlies an array of human diseases such as systemic amyloidosis which is a
      fatal disease caused by misfolding of native globular proteins damaging the
      structure and function of affected organs. Different kind of interactors can
      interfere with the formation of protein dimers and multimers in solution. A very
      special class of interactors are nanoparticles thanks to the extremely efficient
      extension of their interaction surface. In particular citrate-coated gold
      nanoparticles (cit-AuNPs) were recently investigated with amyloidogenic protein
      beta2-microglobulin (beta2m). Here we present the computational studies on two
      challenging models known for their enhanced amyloidogenic propensity, namely
      DeltaN6 and D76N beta2m naturally occurring variants, and disclose the role of
      cit-AuNPs on their fibrillogenesis. The proposed interaction mechanism lies in
      the interference of the cit-AuNPs with the protein dimers at the early stages of
      aggregation, that induces dimer disassembling. As a consequence, natural fibril
      formation can be inhibited. Relying on the comparison between atomistic
      simulations at multiple levels (enhanced sampling molecular dynamics and Brownian
      dynamics) and protein structural characterisation by NMR, we demonstrate that the
      cit-AuNPs interactors are able to inhibit protein dimer assembling. As a
      consequence, the natural fibril formation is also inhibited, as found in
      experiment.

PMID- 29469915
TI  - Blood-pressure lowering efficacy of winged bean seed hydrolysate in spontaneously
      hypertensive rats, peptide characterization and a toxicity study in Sprague
      Dawley rats.
AB  - Winged bean seed (WBS) is an underutilized tropical crop. The current study
      evaluates its potential to reduce blood pressure (BP) in spontaneously
      hypertensive rats and finds that it reduces BP significantly, in a dose-dependent
      manner. Five peptides with the sequences, RGVFPCLK, TQLDLPTQ, EPALVP, MRSVVT and
      DMKP, have been characterized in terms of their stability against ACE via in
      vitro and in silico modelling. All peptides exhibited IC50 values between 0.019
      and 6.885 mM and various inhibitory modes, including substrate, prodrug and true
      inhibitor modes. The toxicity status of non-Current Good Manufacturing Practice
      (non-CGMP) peptides is evaluated and the results show that such peptides are
      toxic, and thus are not suitable to be tested in animals, particularly in
      repeated-dose studies. In short, WBS hydrolysate demonstrated in vitro ACE
      inhibitory properties and in vivo blood pressure lowering efficacy in rat models,
      fostering its potential as a functional food ingredient. Non-CGMP grade peptides
      are toxic and unfit for testing in animal models.

PMID- 29469917
TI  - Metamagnetism stabilized giant magnetoelectric coupling in ferroelectric xBaTiO3
      (1 - x)BiCoO3 solid solution.
AB  - In order to establish the correlation between the magnetoelectric coupling and
      magnetic instability, we have studied the structural, magnetic, and ferroelectric
      properties of BaTiO3 modified BiCoO3i.e. xBaTiO3-(1 - x)BiCoO3 as a function of
      BaTiO3 concentration (x) and volume from a series of general-gradient-corrected
      (GGA), GGA plus onsite Coulomb repulsion (U), full potential, spin-density
      functional band-structure calculations within the framework of density functional
      theory along with synchrotron X-ray diffraction and magnetic measurement studies.
      G-type antiferromagnetic ordering was found to be energetically favorable among
      all the considered magnetic configurations for x < 0.45 and higher concentrations
      stabilize with nonmagnetic (NM) states. We observe metamagnetic spin state
      transitions associated with paraelectric to ferroelectric transitions as a
      function of volume and x using synchrotron diffraction and computational studies,
      indicating a strong magnetoelectric coupling. Specifically for x = 0.33
      composition, a pressure induced high spin (HS) to low spin (LS) transition occurs
      when the volume is compressed below 2.5%. Our orbital-projected density of states
      show a HS state for Co3+ in the ferroelectric ground state for x < 0.45 and the
      corresponding paraelectric phase is stable in the NM state due to the
      stabilization of LS state as evident from our fixed-spin-moment calculations and
      magnetic measurements. The nature of chemical bonding has been studied using
      partial density of states, electron localization function, and Born effective
      charge analysis. High values of spontaneous ferroelectric polarizations are
      predicted for lower x values which inversely vary with x because of the reduction
      of tetragonality (c/a) with increase in x which indicates the presence of both
      spin-lattice and ferroelectricity-lattice coupling. Our partial polarization
      analysis shows that not only the lone pair at Bi sites but also the d0-ness of
      Ti4+ ions contribute to the net polarization. Moreover, we find that the HS-LS
      transition point and magnetoelectric coupling strength can be varied by x.

PMID- 29469921
TI  - Enhanced chiral recognition by gamma-cyclodextrin-cucurbit[6]uril-cowheeled
      [4]pseudorotaxanes.
AB  - Mixing gamma-cyclodextrin (gamma-CD), cucurbit[6]uril (CB[6]) and tetraammonium
      bearing axles together led to a spontaneous formation of gamma-CD-CB[6]-cowheeled
      [4]pseudorotaxanes. The well-defined unsymmetrical cavities thus formed enhance
      the binding affinity towards chiral amines by factors of several hundreds and
      show remarkably improved chiral discrimination.

PMID- 29469923
TI  - Revealing the nature of low-temperature photoluminescence peaks by laser
      treatment in van der Waals epitaxially grown WS2 monolayers.
AB  - Monolayers of transition metal dichalcogenides (TMD) are promising materials for
      optoelectronics devices. However, one of the challenges is to fabricate large
      scale growth of high quality TMD monolayers with the desired properties in order
      to expand their use in potential applications. Here, we demonstrate large-scale
      tungsten disulfide (WS2) monolayers grown by van der Waals Epitaxy (VdWE). We
      show that, in addition to the large structural uniformity and homogeneity of
      these samples, their optical properties are very sensitive to laser irradiation.
      We observe a time instability in the photoluminescence (PL) emission at low
      temperatures in the scale of seconds to minutes. Interestingly, this change of
      the PL spectra with time, which is due to laser induced carrier doping, is
      employed to successfully distinguish the emission of two negatively charged
      bright excitons. Furthermore, we also detect blinking sharp bound exciton
      emissions which are usually attractive for single photon sources. Our findings
      contribute to a deeper understanding of this complex carrier dynamics induced by
      laser irradiation which is very important for future optoelectronic devices based
      on large scale TMD monolayers.

PMID- 29469925
TI  - How old is too old for cochlear implantation for congenital bilateral
      sensorineural hearing loss?

PMID- 29469924
TI  - T-cell-depleted haploidentical stem cell transplantation results improve with
      time in adults with acute leukemia: A study from the Acute Leukemia Working Party
      of the European Society of Blood and Marrow Transplantation (EBMT).
AB  - BACKGROUND: T-cell-depleted, haploidentical transplantations (haplos) are
      commonly offered to patients who have high-risk, acute leukemia in the absence of
      a human leukocyte antigen (HLA) full-matched donor. METHODS: To determine the
      effect of transplantation period, the authors divided 308 adults with de novo,
      acute leukemia who underwent T-cell-depleted haplo from 2005 to 2015 into 2
      groups, according the year in which they underwent transplantation (2005-2011 [n
      = 191] and 2012-2015 [n = 117]). RESULTS: The median age was 41 years in patients
      who underwent transplantation before 2012 and 46 years in those who underwent
      transplantation after 2012 (P = .04). Most patients had acute myeloid leukemia
      (75% vs 69%; P = .26) and were in first complete remission (CR1) (55% vs 64%; P =
      .12) at the time of transplantation. The cumulative incidence of grade 2, 3, and
      4 acute graft-versus-host disease (GvHD) and chronic GvHD were not different
      between the 2 groups (acute GvHD: 20% vs 22% cumulative incidence in patients who
      underwent haplo before and after 2012, respectively [P = .67]; chronic GvHD: 19%
      vs 11% cumulative incidence, respectively; P = .12]. The 2-year relapse incidence
      was 20%, the nonrelapse mortality (NRM) rate was 48%, and no difference was
      observed over time (21% vs 19% [P = .72] and 54% vs 38% [P = .11] for patients
      who underwent haplo before and after 2012, respectively). The main cause of NRM
      was infection. Haplo after 2012 (hazard ratio [HR], 0.57; P = .01), younger age
      (HR, 0.82; P = .02), and receipt of a reduced-intensity conditioning (RIC)
      regimen (HR, 0.53; P = .01) were independently associated with lower NRM. The 2
      year overall survival rate was 36% and improved after 2012 (29% vs 47% before
      2012; P = .02); and it was higher for patients who underwent transplantation in
      CR1 (41% vs 29%; P = .01). In multivariate analysis, haplo after 2012 (HR, 0.54;
      P = .003) and receipt of a RIC regimen (HR, 0.54; P = .005) were independently
      associated with better overall survival. Similarly, leukemia-free survival and
      GvHD-free/relapse-free survival (GRFS) improved over time: the leukemia-free
      survival rate was 31% (25% vs 43% in the groups who underwent transplantation
      before and after 2012, respectively; P = .05), and the GRFS rate was 24% (19% vs
      34%, respectively; P = .09). In addition, leukemia-free survival and GRFS
      improved among patients who received a RIC regimen. CONCLUSIONS: The outcome of
      patients with acute leukemia who underwent T-cell-depleted haplo has improved
      over time. Cancer 2018;124:2142-50. (c) 2018 American Cancer Society.

PMID- 29469926
TI  - Folic Acid Supplementation throughout pregnancy: psychological developmental
      benefits for children.
AB  - AIM: To test the effect of folic acid supplements taken throughout pregnancy on
      children's psychosocial development. METHOD: A randomised controlled trial of
      folic acid supplementation in pregnancy, with parental rating using the
      Resiliency Attitudes and Skills Profile (RASP), the Strengths and Difficulties
      Questionnaire (SDQ) and the Trait Emotional Intelligence Questionnaire Child
      Short Form (TEIQue-CSF). Children aged 6-7 whose mothers received folic acid
      throughout pregnancy (n = 22) were compared to those whose mothers only received
      it during the first trimester (n = 17). RESULTS: Children whose mothers received
      the full-term supplement scored significantly higher on emotional intelligence
      and resilience. Hierarchical multiple regression analysis identified folate level
      at 36th gestational week as an important predictor of emotional intelligence (EI)
      and resilience. CONCLUSION: Although conclusions must be drawn with caution, this
      research presents a number of potential implications, the main one being a
      proposed policy recommendation for women to take folic acid for the duration of
      pregnancy rather than stopping at the end of the first trimester. The second is
      the potential for future research to explore the possible psychological and
      social development benefits and in line with this to try and identify the
      explanatory mechanism involved.

PMID- 29469927
TI  - Cost-effectiveness analysis of stent type in endoscopic treatment of gastric leak
      after laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: Gastric leak is the most feared surgical postoperative complication
      after sleeve gastrectomy. An endoscopic procedure is usually required to treat
      the leak. No data are available on the cost-effectiveness of different stent
      types in this procedure. METHODS: Between April 2005 and July 2016, patients with
      a confirmed gastric leak undergoing endoscopic treatment using a covered stent
      (CS) or double-pigtail stent (DPS) were included. The primary objective of the
      study was to assess overall costs of the stent types after primary sleeve
      gastrectomy. Secondary objectives were the cost-effectiveness of each stent type
      expressed as an incremental cost-effectiveness ratio (ICER); the incremental net
      benefit; the probability of efficiency, defined as the probability of being cost
      effective at a threshold of ?30 000, and identification of the key drivers of
      ICER derived from a multivariable analysis. RESULTS: One hundred and twelve
      patients were enrolled. The overall mean costs of gastric leak were ?22 470; the
      mean(s.d.) cost was ?24 916(12 212) in the CS arm and ?20 024(3352) in the DPS
      arm (P = 0.018). DPS was more cost-effective than CS (ICER ?4743 per endoscopic
      procedure avoided), with an incremental net benefit of ?25 257 and a 27 per cent
      probability of efficiency. Key drivers of the ICER were the inpatient ward after
      diagnosis of gastric leak (surgery versus internal medicine), type of institution
      (private versus public) and duration of hospital stay per endoscopic procedure.
      CONCLUSION: DPS for the treatment of gastric leak is more cost-effective than CS
      and should be proposed as the standard regimen whenever possible.

PMID- 29469928
TI  - Obstructive Sleep Apnea and Neurocognitive Dysfunction in Edentulous Patients.
AB  - PURPOSE: To record the incidence of cognitive dysfunction in edentulous patients
      suffering from obstructive sleep apnea (OSA) and establish a plausible hypothesis
      to explain the correlation of cognitive dysfunction and OSA. MATERIALS AND
      METHODS: In this study, 315 edentulous patients (aged 60 to 65 years) visiting
      the outpatient department at Saraswati Dental College, Lucknow were recruited
      from January 2013 to October 2015. Prosthodontic Diagnostic Index (PDI)
      classification was used to assess the intraoral condition to relate it with the
      span of edentulousness. The BERLIN questionnaire and Epworth Sleepiness Scales
      were used to diagnose sleep-disordered breathing, following which the patients
      were put through all-night polysomnography. The apnea-hypopnea index (AHI) scores
      were derived. Mild and moderate OSA patients were classified into mild, moderate,
      and severe cognitive dysfunction based on SGRQ-C and SCD. Data were tabulated
      according to a new classification (Cognitive Dysfunction of Dental Sleep Medicine
      Patients [CDDSMP] Classification) designed specifically for this study. Data were
      analyzed using SPSS v15.0. Scores were tabulated as mean +/- SD and median [IQR]
      values. Change from baseline was analyzed using Wilcoxon signed rank test.
      RESULTS: Mean scores at different time intervals were 3.03 +/- 1.76 (3 months),
      2.98 +/- 1.80 (6 months), and 2.81 +/- 1.84 (9 months). The median [IQR] values
      of scores at all time intervals except 9 months were 3 [1 to 5]. At 9 months,
      median [IQR] was 2 [1 to 5]. A significant change in scores was observed in the 3
      month interval (p <= 0.001). CONCLUSIONS: The severity of OSA and neurocognitive
      dysfunction could be directly related to the PDI classification and the span of
      edentulousness of the patient and modified mandibular advancement device
      treatment significantly improved the patients' condition, which was reflective
      from 3 months post-intervention itself.

PMID- 29469929
TI  - Domperidone for increasing breast milk volume in mothers expressing breast milk
      for their preterm infants: a systematic review and meta-analysis.
AB  - BACKGROUND: Mothers of preterm infants often struggle to produce enough breast
      milk to meet the nutritional needs of their infant. Galactagogues such as
      domperidone are often prescribed to increase breast milk supply but evidence
      supporting their role in clinical practice is uncertain. OBJECTIVE: To evaluate
      the efficacy and safety of domperidone for increasing breast milk volume in
      mothers expressing breast milk for their preterm infants. SEARCH STRATEGY:
      MEDLINE, Embase and Web of Science were searched without language restrictions
      from first publication until January 2017. Bibliographies of articles and reviews
      were hand-searched for additional reports. SELECTION CRITERIA: Randomised
      controlled trials that compared domperidone with placebo in mothers of preterm
      infants (<37 weeks' gestation) experiencing insufficient milk supply. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed studies for
      inclusion, extracted data and evaluated study quality. Differences in breast milk
      volume and adverse events were combined using fixed effects meta-analysis. MAIN
      RESULTS: The pooled analysis of five trials consisting of 194 women demonstrated
      a moderate increase in daily breast milk volume of 88.3 ml/day (95% CI 56.8
      119.8) with the use of domperidone compared with placebo. No difference was
      evident with respect to maternal adverse events (odds ratio 1.05, 95% CI 0.65
      1.71), with no reported cases of prolonged QTc syndrome or sudden cardiac death.
      Sensitivity analyses showed no important differences in the estimates of effects.
      CONCLUSIONS: Domperidone is well tolerated and results in a moderate short-term
      increase in expressed breast milk volume among mothers of preterm infants
      previously identified as having insufficient breast milk supply. TWEETABLE
      ABSTRACT: Domperidone leads to short-term improvements in breast milk volume in
      mothers of preterm infants.

PMID- 29469930
TI  - Psychometric properties of the brief loss of control over eating scale (LOCES-B)
      in early adolescents.
AB  - OBJECTIVE: The purpose of this study was to evaluate the psychometric properties
      of the brief loss of control over eating scale (LOCES-B) in a community sample of
      adolescents. METHOD: Participants were 1,116 adolescents (11-15 years; 53% girls;
      53% non-Hispanic White) recruited from middle schools in the Northeast United
      States. Participants were administered self-report surveys during school in the
      fall of 2016. RESULTS: Confirmatory factor analyses indicated that the LOCES-B
      total score was unidimensional, which was invariant across gender and weight
      status. The LOCES-B had excellent internal consistency (alpha = .92). The LOCES-B
      total score had large, positive relationships with the frequency of LOC eating
      episodes, objective bulimic episodes, and subjective bulimic episodes, and a
      small, positive relationship with objective overeating episode frequency. After
      adjusting for demographics, anthropometrics, and LOC eating frequency,
      adolescents reporting higher scores on the LOCES-B total score had greater body
      image dissatisfaction, more internalizing symptoms, and lower trait effortful
      control. DISCUSSION: Findings suggested that the LOCES-B is a reliable and valid
      measure of LOC eating in early adolescents. The availability of the LOCES-B has
      the potential to elucidate the developmental trajectories, predictors, and
      outcomes of LOC eating across the full severity spectrum in large cohort studies
      of youth.

PMID- 29469931
TI  - Development of Portable Flow-Through Electrochemical Sanitizing Unit to Generate
      Near Neutral Electrolyzed Water.
AB  - : We developed a portable flow-through, electrochemical sanitizing unit to
      produce near neutral pH electrolyzed water (producing NEW). Two methods of
      redirecting cathode yields back to the anode chamber and redirecting anode yields
      the cathode chamber were used. The NEW yields were evaluated, including: free
      available chlorine (FAC), oxidation-reduction potential (ORP), and pH. The
      performances of 2 electrodes (RuO2 -IrO2 /TiO2 and IrO2 -Ta2 O5 /TiO2 ) were
      investigated. The unit produced NEW at pH 6.46 to 7.17, an ORP of 805.5 to 895.8
      mV, and FAC of 3.7 to 82.0 mg/L. The NEW produced by redirecting cathode yields
      had stronger bactericidal effects than the NEW produced by redirecting anode
      yields or NEW produced by mixing the commercial unit's anode and cathode product
      (P < 0.05). Electron spin resonance results showed hydroxyl free radicals and
      superoxide anion free radicals were present in the NEW produced by developed
      unit. The NEW generator is a promising sanitizing unit for consumers and the food
      industry to control foodborne pathogens. PRACTICAL APPLICATION: Current
      commercial NEW-producing units are quite large and are not convenient for family
      using. The developed portable flow-through, NEW-producing unit has great
      potential in a wide range of applications, such as organic farm, households, and
      small food industries. The examined sanitizing treatments showed effective
      control of Escherichia coli O157:H7 and Listeria monocytogenes.

PMID- 29469932
TI  - High control rates of proton- and carbon-ion-beam treatment with intensity
      modulated active raster scanning in 101 patients with skull base chondrosarcoma
      at the Heidelberg Ion Beam Therapy Center.
AB  - BACKGROUND: The current study compares the results of irradiation with protons
      and irradiation with carbon ions via a raster scan technique in patients with G1
      and G2 skull base chondrosarcomas. METHODS: Between 2009 and 2014, a total of 101
      patients (40 men and 61 women) with a median age of 44 years (range, 19-77 years)
      were irradiated with carbon ions (79 patients) or protons (22 patients) via a
      raster scan technique at the Heidelberg Ion Beam Therapy Center. The median total
      dose was 60 Gy (relative biological effectiveness [RBE]) at 3 Gy per fraction for
      carbon ions and 70 Gy (RBE) at 2 Gy per fraction for protons. The median boost
      planning target volume was 38 cm3 (range, 8-133 cm3 ). Overall survival (OS) and
      local control (LC) were evaluated with the Kaplan-Meier method. RESULTS: The
      median follow-up period was 40 months (range, 0.8-78.1 months). At the start of
      the irradiation, all patients had residual macroscopic tumors. Five patients (5%)
      developed a local recurrence during the follow-up. The 1-, 2-, and 4-year LC
      rates were 100%, 100%, and 100%, respectively, for protons and 98.6%, 97.2%, and
      90.5%, respectively, for carbon ions. The OS rates during the same periods of
      time were 100%, 100%, and 100%, respectively, for protons and 100%, 98.5%, and
      92.9%, respectively, for carbon ions. An age <= 44 years was associated with a
      trend for a better outcome. No toxicity worse than Common Toxicity Criteria grade
      3 was observed after treatment. CONCLUSIONS: No significant difference between
      carbon ions and protons in the therapy of skull base chondrosarcoma could be
      detected in these initial retrospective results. Cancer 2018;124:2036-44. (c)
      2018 American Cancer Society.

PMID- 29469933
TI  - Implicit attitudes toward eating stimuli differentiate eating disorder and non
      eating disorder groups and predict eating disorder behaviors.
AB  - OBJECTIVE: The current study tested whether people with and without eating
      disorders (EDs) varied in their implicit attitudes toward ED-relevant stimuli.
      Additionally, the study tested whether implicit evaluations of ED-relevant
      stimuli predicted ED symptoms and behaviors over a 4-week interval. METHOD:
      Participants were people without EDs (N = 85) and people seeking treatment for
      EDs (N = 92). All participants completed self-report questionnaires and a version
      of the affect misattribution procedure (AMP) at baseline. The AMP indexed
      implicit evaluations of average body stimuli, eating stimuli, and ED-symptom
      stimuli. Participants with EDs completed weekly follow-up measures of ED symptoms
      and behaviors for 4 weeks. RESULTS: Contrary to predictions, the anorexia nervosa
      (AN) group did not differ from the no ED group on implicit attitudes toward ED
      symptom stimuli, and the bulimia nervosa (BN) group had less positive implicit
      attitudes toward ED-symptom stimuli relative to the no ED group. In line with
      predictions, people with AN and BN had more negative implicit attitudes toward
      average body and eating stimuli relative to the no ED group. In addition, among
      the ED group more negative implicit attitudes toward eating stimuli predicted ED
      symptoms and behaviors 4 weeks later, over and above baseline ED symptoms and
      behaviors. DISCUSSION: Taken together, implicit evaluations of eating stimuli
      differentiated people with AN and BN from people without EDs and longitudinally
      predicted ED symptoms and behaviors. Interventions that increase implicit liking
      of eating-related stimuli may reduce ED behaviors.

PMID- 29469934
TI  - Microbial Quality and Shelf Life of Blueberry Puree Developed Using Cavitation
      Technology.
AB  - : Blueberry puree was developed using hydrodynamic cavitation technology. The
      product was made from entire blueberries without adding any food additives. In
      this study, microbial reduction following each processing stage (at the industry
      setting) and after product pasteurization at 86, 88, 90, 92, 94, and 96  degrees
      C was investigated. Microbial quality including total plate counts, yeast and
      molds, and heat-resistant molds counts was determined. Shelf life of pasteurized
      products stored for up to 24 weeks at room temperature were assessed for
      microbial quality, soluble solids ( degrees Brix), titratable acidity (citric
      acid %), pH, viscosity (cP) and flow rate (cm/30 s). Our results indicated that
      heat-resistant molds, initially present in frozen blueberries with counts at 2.03
      log CFU/200g, were totally inactivated at 94 to 96  degrees C with 1 to 2 min
      holding time. Shelf life study showed that no product spoilage was caused by
      bacteria, yeasts and heat-resistant molds along with non-significant changes of
      textural characteristics. This study provided useful information for the food
      industry to develop variety of fruit puree products with no wastes of fruit
      materials. PRACTICAL APPLICATION: This study provides useful information for the
      food industry to develop safe liquid food products using cavitation technology
      without wasting any raw materials.

PMID- 29469935
TI  - Are children with chronic illnesses requiring dietary therapy at risk for
      disordered eating or eating disorders? A systematic review.
AB  - OBJECTIVE: Pediatric chronic illnesses (CI) can affect a child's mental health.
      Chronic illnesses with treatment regimens that specify a therapeutic diet may
      place the child at increased risk for disordered eating and specific eating
      disorders (ED). The aim of this review is to examine the relation between diet
      treated CI and disordered eating and to determine the order of onset to infer
      directionality. Diet-treated CI is hypothesized to precede and to be associated
      with disordered eating. METHOD: A comprehensive search of empirical articles that
      examine the relation between diet-treated CI (diabetes, cystic fibrosis, celiac
      disease, gastrointestinal disorders, and inflammatory bowel diseases) and
      disordered eating was conducted in Medline and PsycINFO using the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A table of
      the sample's characteristics, ED measures, major pertinent findings, and the
      onset of CI in relation to ED were provided. RESULTS: Diet-treated CI was
      associated with disordered eating and ED. Diet-treated CI had onset prior to
      disordered eating in most studies, except for inflammatory bowel diseases.
      Disordered eating and unhealthy weight management practices put children at risk
      for poor medical outcomes. DISCUSSION: Interventions for diet-treated CI require
      a focus on diet and weight, but may increase the risk for disordered eating.
      Future research is needed to elucidate the mechanisms that transform standard
      treatment practices into pathological eating, including characteristics and
      behaviors of the child, parents/care providers, family, and treatment providers.

PMID- 29469936
TI  - 2D-3D registration for cranial radiation therapy using a 3D kV CBCT and a single
      limited field-of-view 2D kV radiograph.
AB  - PURPOSE: We present and evaluate a fully automated 2D-3D intensity-based
      registration framework using a single limited field-of-view (FOV) 2D kV
      radiograph and a 3D kV CBCT for 3D estimation of patient setup errors during
      brain radiotherapy. METHODS: We evaluated two similarity measures, the Pearson
      correlation coefficient on image intensity values (ICC) and maximum likelihood
      measure with Gaussian noise (MLG), derived from the statistics of transmission
      images. Pose determination experiments were conducted on 2D kV radiographs in the
      anterior-posterior (AP) and left lateral (LL) views and 3D kV CBCTs of an
      anthropomorphic head phantom. In order to minimize radiation exposure and exclude
      nonrigid structures from the registration, limited FOV 2D kV radiographs were
      employed. A spatial frequency band useful for the 2D-3D registration was
      identified from the bone-to-no-bone spectral ratio (BNBSR) of digitally
      reconstructed radiographs (DRRs) computed from the 3D kV planning CT of the
      phantom. The images being registered were filtered accordingly prior to
      computation of the similarity measures. We evaluated the registration accuracy
      achievable with a single 2D kV radiograph and with the registration results from
      the AP and LL views combined. We also compared the performance of the 2D-3D
      registration solutions proposed to that of a commercial 3D-3D registration
      algorithm, which used the entire skull for the registration. The ground truth was
      determined from markers affixed to the phantom and visible in the CBCT images.
      RESULTS: The accuracy of the 2D-3D registration solutions, as quantified by the
      root mean squared value of the target registration error (TRE) calculated over a
      radius of 3 cm for all poses tested, was ICCAP : 0.56 mm, MLGAP : 0.74 mm, ICCLL
      : 0.57 mm, MLGLL : 0.54 mm, ICC (AP and LL combined): 0.19 mm, and MLG (AP and LL
      combined): 0.21 mm. The accuracy of the 3D-3D registration algorithm was 0.27 mm.
      There was no significant difference in mean TRE for the 2D-3D registration
      algorithms using a single 2D kV radiograph with similarity measure and image view
      point. There was no significant difference in mean TRE between ICCLL , MLGLL ,
      ICC (AP and LL combined), MLG (AP and LL combined), and the 3D-3D registration
      algorithm despite the smaller FOV used for the 2D-3D registration. While
      submillimeter registration accuracy was obtained with both ICC and MLG using a
      single 2D kV radiograph, combining the results from the two projection views
      resulted in a significantly smaller (P<=0.05) mean TRE. CONCLUSIONS: Our results
      indicate that it is possible to achieve submillimeter registration accuracy with
      both ICC and MLG using either single or dual limited FOV 2D kV radiographs of the
      head in the AP and LL views. The registration accuracy suggests that the 2D-3D
      registration solutions presented are suitable for the estimation of patient setup
      errors not only during conventional brain radiation therapy, but also during
      stereotactic procedures and proton radiation therapy where tighter setup margins
      are required.

PMID- 29469937
TI  - Radiomic features on MRI enable risk categorization of prostate cancer patients
      on active surveillance: Preliminary findings.
AB  - BACKGROUND: Radiomic analysis is defined as computationally extracting features
      from radiographic images for quantitatively characterizing disease patterns.
      There has been recent interest in examining the use of MRI for identifying
      prostate cancer (PCa) aggressiveness in patients on active surveillance (AS).
      PURPOSE: To evaluate the performance of MRI-based radiomic features in
      identifying the presence or absence of clinically significant PCa in AS patients.
      STUDY TYPE: Retrospective. SUBJECTS MODEL: MRI/TRUS (transperineal grid
      ultrasound) fusion-guided biopsy was performed for 56 PCa patients on AS who had
      undergone prebiopsy. FIELD STRENGTH/SEQUENCE: 3T, T2 -weighted (T2 w) and
      diffusion-weighted (DW) MRI. ASSESSMENT: A pathologist histopathologically
      defined the presence of clinically significant disease. A radiologist manually
      delineated lesions on T2 w-MRs. Then three radiologists assessed MRIs using
      PIRADS v2.0 guidelines. Tumors were categorized into four groups: MRI-negative
      biopsy-negative (Group 1, N = 15), MRI-positive-biopsy-positive (Group 2, N =
      16), MRI-negative-biopsy-positive (Group 3, N = 10), and MRI-positive-biopsy
      negative (Group 4, N = 15). In all, 308 radiomic features (First-order
      statistics, Gabor, Laws Energy, and Haralick) were extracted from within the
      annotated lesions on T2 w images and apparent diffusion coefficient (ADC) maps.
      The top 10 features associated with clinically significant tumors were identified
      using minimum-redundancy-maximum-relevance and used to construct three machine
      learning models that were independently evaluated for their ability to identify
      the presence and absence of clinically significant disease. STATISTICAL TESTS:
      Wilcoxon rank-sum tests with P < 0.05 considered statistically significant.
      RESULTS: Seven T2 w-based (First-order Statistics, Haralick, Laws, and Gabor) and
      three ADC-based radiomic features (Laws, Gradient and Sobel) exhibited
      statistically significant differences (P < 0.001) between malignant and normal
      regions in the training groups. The three constructed models yielded overall
      accuracy improvement of 33, 60, 80% and 30, 40, 60% for patients in testing
      groups, when compared to PIRADS v2.0 alone. DATA CONCLUSION: Radiomic features
      could help in identifying the presence and absence of clinically significant
      disease in AS patients when PIRADS v2.0 assessment on MRI contradicted pathology
      findings of MRI-TRUS prostate biopsies. LEVEL OF EVIDENCE: 3 Technical Efficacy:
      Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 29469938
TI  - Strength and cardiometabolic risk in young adults: The mediator role of aerobic
      fitness and waist circumference.
AB  - The aim of this study was to analyze the mediation role of cardiorespiratory
      fitness and waist circumference in the association between muscular strength and
      cardiometabolic risk. A cross-sectional study involved first-year college
      students (n = 370) from a Spanish public university was performed. We measured
      weight, height, waist circumference, blood pressure, biochemical variables,
      maximum handgrip strength assessment, and cardiorespiratory fitness. We
      calculated handgrip dynamometry/weight and a previously validated cardiometabolic
      risk index. Analysis of covariance models was conducted to test differences in
      cardiometabolic risk values across muscular strength, cardiorespiratory fitness,
      and waist circumference categories, controlling for confounders. Hayes' PROCESS
      macro was used for the multiple mediation analysis. The relationship between
      muscular strength and cardiometabolic risk did not remain significant (c' = 1.76
      [1.4]; P > .05) in a multiple serial bootstrapped mediation model including
      cardiorespiratory fitness and waist circumference as mediators when controlling
      for age and sex. According to the indirect effect, the significant paths in the
      model mediating this relationship between muscular strength and cardiometabolic
      risk index were as follows: muscular strength -> waist circumference ->
      cardiometabolic risk index (-4.899; 95% CI: -6.690; -3.450) and muscular strength
      -> cardiorespiratory fitness -> waist circumference -> cardiometabolic risk index
      (-0.720; 95% CI: -1.316; -0.360). Both cardiorespiratory fitness and waist
      circumference mediate the association between muscular strength and
      cardiometabolic risk in young adults. Thus, our results place cardiorespiratory
      fitness and waist circumference as the main targets of physical activity
      programmes aimed at preventing cardiometabolic diseases.

PMID- 29469939
TI  - Proximate mechanisms of the differences in reproductive success of males bearing
      different alleles of Pgdh - a gene involved in a sexual conflict in bulb mite.
AB  - Enzyme polymorphism in phosphogluconate dehydrogenase (Pgdh) is a striking
      example of single gene polymorphism involved in sexual conflict in bulb mite
      Rhizoglyphus robini. Males homozygous for the S Pgdh allele were shown to achieve
      higher reproductive success than FF homozygous males, while negatively
      influencing fecundity of their female partners. Here, we investigate proximate
      mechanisms responsible for the increased reproductive success of SS males and
      find that the S allele is associated with shorter time until copulation, higher
      copulation frequency and increased sperm production. We also show that Pgdh
      alleles are probably codominant, with SS males gaining the highest reproductive
      success, FF males - the lowest - and FS-heterozygous males taking an intermediate
      position in all fitness parameters differentiating males of different genotypes.
      Additionally, we confirm the negative effect that S-bearing males impose on the
      fecundity of females they mate with, showing a clear pattern of interlocus sexual
      conflict. We discuss that this effect is probably associated with increased
      copulation frequency. Whereas, contrary to what we have predicted, the S allele
      does not cause increased general male mobility, we speculate that the S allele
      bearing males are more efficient in forcing copulation and/or detecting females.

PMID- 29469940
TI  - Different qualifiers of AUS/FLUS thyroid FNA have distinct BRAF, RAS, RET/PTC,
      and PAX8/PPARg alterations.
AB  - BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology category of
      atypia of undetermined significance/follicular lesion of undetermined
      significance (AUS/FLUS) includes fine-needle aspiration (FNA) specimens that
      cannot straightforwardly be classified as benign or malignant. To determine
      whether morphological subcategorization based on atypia qualifiers and molecular
      testing could improve malignancy risk stratification of AUS/FLUS patients, this
      study assessed the correlation between these qualifiers and the molecular
      alterations commonly harbored by thyroid neoplasms. METHODS: A total of 162
      AUS/FLUS cases were subcategorized by atypia qualifiers (Hurthle cell changes,
      architectural atypia, and cytologic atypia [CyA]) and were tested for BRAF, N-H
      KRAS, RET/PTC, and paired box 8 (PAX8)/peroxisome proliferator activated receptor
      gamma (PPARg) mutations. RESULTS: CyA was observed more frequently in mutation
      positive AUS/FLUS (14 of 37 [37.84%]) than mutation-negative AUS/FLUS (20 of 125
      [16.00%]; P < .0084), and it specifically harbored the BRAFV600E point mutation.
      Malignancy was confirmed in the available follow-up. Conversely, although RAS was
      the most frequent mutation identified in AUS/FLUS FNA specimens (26 of 37 cases
      [70.27%]; P < .0001), it was distributed across various AUS/FLUS subcategories
      and was not significantly associated with a specific atypia qualifier or
      malignant outcome according to the available follow-up. Rearrangements of both
      RET/PTC (n = 1) and PAX8/PPARg (n = 3) were rarely retrieved in the FNA samples.
      CONCLUSIONS: BRAF and RAS mutations are associated with different AUS/FLUS
      qualifiers and hence have different risks of malignancy. Consequently, a hybrid
      molecular and morphological subcategorization system could improve the malignancy
      risk stratification of thyroid FNA samples diagnosed as AUS/FLUS. Cancer
      Cytopathol 2018;126:317-25. (c) 2018 American Cancer Society.

PMID- 29469941
TI  - Extensive colonic mucosal defect induced by mesalamine.

PMID- 29469942
TI  - Whole-tumor apparent diffusion coefficient (ADC) histogram analysis to
      differentiate benign peripheral neurogenic tumors from soft tissue sarcomas.
AB  - BACKGROUND: Apparent diffusion coefficient (ADC) histogram analyses have been
      used to differentiate tumor grades and predict therapeutic responses in various
      anatomic sites with moderate success. PURPOSE: To determine the ability of
      diffusion-weighted imaging (DWI) with a whole-tumor ADC histogram analysis to
      differentiate benign peripheral neurogenic tumors (BPNTs) from soft tissue
      sarcomas (STSs). STUDY TYPE: Retrospective study, single institution. SUBJECTS:
      In all, 25 BPNTs and 31 STSs. FIELD STRENGTH/SEQUENCE: Two-b value DWI (b-values
      = 0, 1000s/mm2 ) was at 3.0T. ASSESSMENT: The histogram parameters of whole-tumor
      for ADC were calculated by two radiologists and compared between BPNTs and STSs.
      STATISTICAL TESTS: Nonparametric tests were performed for comparisons between
      BPNTs and STSs. P < 0.05 was considered statistically significant. The ability of
      each parameter to differentiate STSs from BPNTs was evaluated using area under
      the curve (AUC) values derived from a receiver operating characteristic curve
      analysis. RESULTS: The mean ADC and all percentile parameters were significantly
      lower in STSs than in BPNTs (P < 0.001-0.009), with AUCs of 0.703-0.773. However,
      the coefficient of variation (P = 0.020 and AUC = 0.682) and skewness (P = 0.012
      and AUC = 0.697) were significantly higher in STSs than in BPNTs. Kurtosis (P =
      0.295) and entropy (P = 0.604) did not differ significantly between BPNTs and
      STSs. DATA CONCLUSION: Whole-tumor ADC histogram parameters except kurtosis and
      entropy differed significantly between BPNTs and STSs. LEVEL OF EVIDENCE: 3
      Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 29469943
TI  - Effects of Diagnostic Work-Up on Medical Decision-Making for Canine Urinary Tract
      Infection: An Observational Study in Danish Small Animal Practices.
AB  - BACKGROUND: Clinical signs of urinary tract disease in dogs often lead to
      prescription of antibiotics. Appropriate diagnostic work-up could optimize
      treatment and reduce the risk of inappropriate use of antibiotics.
      HYPOTHESIS/OBJECTIVES: To describe and evaluate the impact of diagnostic work-up
      on decision to treat (DTT) and choice of antibiotic treatment (COT) for dogs
      presenting with clinical signs of urinary tract disease. ANIMALS: One hundred and
      fifty-one dogs presenting to 52 Danish veterinary practices. METHODS:
      Prospective, observational study. Clinical signs, diagnostic work-up, and
      prescriptions were recorded. Urine samples were submitted to a reference
      laboratory for quantitative bacterial culture (QBC) and susceptibility testing.
      The laboratory results were used as reference for assessing the appropriateness
      of DTT and COT. RESULTS: In the majority of dogs, veterinarians performed
      dipstick (99%), microscopic examination of urine (80%) and bacterial culture
      (56%). Fifty-one percent of dogs had urinary tract infection (UTI) based on
      reference QBC. Appropriate DTT was made for 62% of the dogs, while 36% were over
      prescribed and 2% under-prescribed. Inappropriate use of second-line agents was
      found in 57% of the UTI cases. Performing microscopy-but not culture
      significantly impacted DTT (P = 0.039) while no difference was seen in COT (P =
      0.67). The accuracy of in-house microscopy and culture were 64.5 and 77%,
      respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Over-prescription of
      antibiotics was common among dogs with suspected UTI, regardless of the
      diagnostic work-up performed. Test inaccuracy under practice conditions and
      incoherence between diagnostic test results and decision-making both explained
      inappropriate and unnecessary use of antibiotics.

PMID- 29469944
TI  - Multicentre randomized clinical trial of the effect of chewing gum after
      abdominal surgery.
AB  - BACKGROUND: Postoperative ileus is a common complication of abdominal surgery,
      leading to patient discomfort, morbidity and prolonged postoperative length of
      hospital stay (LOS). Previous studies suggested that chewing gum stimulates bowel
      function after abdominal surgery, but were underpowered to evaluate its effect on
      LOS and did not include enhanced recovery after surgery (ERAS)-based
      perioperative care. This study evaluated whether chewing gum after elective
      abdominal surgery reduces LOS and time to bowel recovery in the setting of ERAS
      based perioperative care. METHODS: A multicentre RCT was performed of patients
      over 18 years of age undergoing abdominal surgery in 12 hospitals. Standard
      postoperative care (control group) was compared with chewing gum three times a
      day for 30 min in addition to standard postoperative care. Randomization was
      computer-generated; allocation was concealed. The primary outcome was
      postoperative LOS. Secondary outcomes were time to bowel recovery and 30-day
      complications. RESULTS: Between 2011 to 2015, 1000 patients were assigned to
      chewing gum and 1000 to the control arm. Median LOS did not differ: 7 days in
      both arms (P = 0.364). Neither was any difference found in time to flatus (24 h
      in control group versus 23 h with chewing gum; P = 0.873) or time to defaecation
      (60 versus 52 h respectively; P = 0.562). The rate of 30-day complications was
      not significantly different either. CONCLUSION: The addition of chewing gum to an
      ERAS postoperative care pathway after elective abdominal surgery does not reduce
      the LOS, time to bowel recovery or the rate of postoperative complications.
      Registration number: NTR2594 (Netherlands Trial Register).

PMID- 29469945
TI  - Extravillous trophoblast invasion in placenta accreta is associated with
      differential local expression of angiogenic and growth factors: a cross-sectional
      study.
AB  - OBJECTIVE: Placenta accreta is clinically associated with maternal uterine scar.
      Our objective was to investigate the biochemical contribution of maternal
      scarring to hyperinvasive trophoblast. We hypothesised that trophoblast over
      invasion in placenta accreta is associated with aberrant invasion-site signalling
      of growth and angiogenic factors known to be involved in wound healing and
      promotion of cell invasion through the epithelial to mesenchymal cellular
      programme. DESIGN: Cross-sectional series. SETTING: Yale-New Haven Hospital.
      POPULATION: Women with histologically confirmed normal and abnormal placentation.
      METHODS: Placental invasion site tissue sections were immunostained for endoglin
      and other angiogenic regulators, and transforming growth factor beta (TGFbeta)
      proteins. Maternal serum endoglin, and the vascular endothelial growth factor
      (VEGF) mediators hypoxia-inducible factor-1alpha (HIF1alpha) and endostatin, were
      assessed using immunoassay. MAIN OUTCOME MEASURES: Differences in median H-score
      by immunostaining and in mean serum level by immunoassay. RESULTS: By
      immunostaining, placenta accreta samples demonstrated intervillous endoglin
      shedding and increased trophoblast expression of its cleavage protein matrix
      metalloproteinase-14. Absent decidual HIF1alpha and endostatin were observed in
      areas of VEGF upregulation. TGFbeta1 was present in myocytes but not in collagen
      bundles into which accreta trophoblast invaded. Maternal serum endoglin decreased
      in praevia and accreta when corrected for gestational age. CONCLUSION: Angiogenic
      and growth factors at the placental invasion site are altered in accreta, both by
      decidual absence and within myometrial scar. We postulate this promotes the
      invasive phenotype of placenta accreta by activating hyperinvasive trophoblast
      and by dysregulating placental vascular remodelling. FUNDING: Yale Department of
      Obstetrics, Gynecology and Reproductive Sciences funds. TWEETABLE ABSTRACT:
      Placenta accreta histology shows dysregulation of angiogenic and growth factors.

PMID- 29469946
TI  - Genome Variations of Evolved Escherichia coli ET8 With a Rhodopsin-Based
      Phototrophic Metabolism.
AB  - We reported that the phototrophic metabolism via plasmid-originated Gloeobacter
      rhodopsin(GR)-expression is improved in Escherichia coli ET5 harboring pKJ606-GR
      by a genomic point mutation (dgcQC1082A ) encoding a transmembrane cell signaling
      protein (Microb. Cell Fact. 16:111, 2017). Another evolved descendant is isolated
      from the chemostat, and the genome variation of the strain named ET8 harboring
      pKJ606-GR is investigated in this study. Whole genome sequencing analysis
      identifies a single point mutation (C3831976A) located in the non-coding upstream
      region of kdtA and an IS4 insertional mutation at galUG706 without any mutations
      in the plasmid. ET8 strain shows enhanced kdtA transcription and no growth in the
      D-galactose or lactose sole carbon sourced minimal media. Size of ET8 strain are
      almost identical to that of the ancestor. Phototrophic growth and proton pumping
      in ET8 expressing GR (ET8 + GR) are increased 1.5-fold and threefold,
      respectively, compared with those in the ancestor (W3110 + GR). To verify the
      effects of the genomic mutations, either the kdtA-upregulation or the galU
      disruption is conducted in the ancestor. Both the kdtA-upregulation and the galU
      disruption result in the drastic increases of proton-pumping. The physiological
      properties arising from the genomic variations of the evolved host with the new
      phototrophic metabolism are further discussed.

PMID- 29469947
TI  - Evaluation of the metabolic capability of primary human hepatocytes in three
      dimensional cultures on microstructural plates.
AB  - The NanoCulture Plate (NCP) is a novel microstructural plate designed as a base
      for the three-dimensional culture of cells/tissues. This study examined whether
      or not the metabolic capability of human primary hepatocytes is well maintained
      during culture on NCPs. The hepatocytes formed aggregates after seeding and their
      ATP content was well maintained during culture for 21 days. Expression of CYP1A2,
      2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 mRNAs was detected throughout the 21-day culture
      period. Addition of CYP substrate drugs (midazolam, diclofenac, lamotrigine and
      acetaminophen) resulted in the formation of multiple metabolites with a
      corresponding decrease in the amounts of the unchanged compounds. The inducers
      omeprazole, phenobarbital and rifampicin increased the levels of CYP1A2, 2B6 and
      3A4 mRNAs by 110-fold, 12.5-fold and 5.4-fold, respectively, at day 2, compared
      with control human hepatocytes. CYP activities were also increased at 2 days
      after inducer treatment (CYP1A2, 2.2-fold; CYP2B6, 20.6-fold; CYP3A4, 3.3-fold).
      The results indicate that the hepatocyte spheroids on NCP have detectable and
      inducible metabolic abilities during the 7-day culture period.

PMID- 29469948
TI  - Sensory Acceptability of Iron-Fortified Red Lentil (Lens culinaris Medik.) Dal.
AB  - : Panelists in Saskatoon, Canada (n = 45) and Dhaka, Bangladesh (n = 98)
      participated in sensory evaluations of the sensory properties of both cooked and
      uncooked dehulled red lentil dal fortified with FeSO4 .7H2 O, NaFeEDTA or FeSO4
      .H2 O at fortificant Fe concentrations of 800, 1,600 (both cooked and uncooked),
      or 2,800 ppm. Appearance, odor, and overall acceptability of cooked and uncooked
      samples were rated using a 9-point hedonic scale (1 = dislike extremely to 9 =
      like extremely). Taste and texture were rated for the cooked samples prepared as
      typical south Asian lentil meals. Significant differences in sensory quality were
      observed among all uncooked and cooked samples at both locations. Overall, scores
      for all sensory attributes and acceptability of uncooked lentil decreased with
      increasing concentration of Fe in the fortificant; however, Fe fortification
      (particularly with NaFeEDTA) had small effects on acceptability. Panelists from
      Saskatoon provided a wider range of scores than those from Bangladesh for all
      attributes of cooked lentil. Overall, sensory evaluation of Fe fortification
      using NaFeEDTA minimally affected consumer perception of color, taste, texture,
      odor, and overall acceptability of cooked lentil. Reliability estimates
      (Cronbach's alpha [CA]) indicated that consumer scores were generally consistent
      for all attributes of all lentil samples (mean CA > 0.80). NaFeEDTA was found to
      be the most suitable Fe fortificant for lentil based on consumer acceptability.
      Consumption of 45 to 50 g of NaFeEDTA-fortified lentil (fortificant Fe
      concentration of 1,600 ppm) per day meets the estimated average requirements
      (EARs) of Fe for humans (10.8 to 29.4 mg). PRACTICAL APPLICATION: Iron
      fortification of dehulled lentil dal may change organoleptic attributes that can
      influence consumer acceptability. Sensory evaluation by consumers helps to
      determine the effect on appearance, odor, taste, texture, and overall
      acceptability of fortified lentils. In this study, consumer acceptability was
      evaluated with panelists who consume lentil regularly. Panelists provided
      significantly different scores for 5 sensory attributes for 10 uncooked and 3
      cooked lentil samples. Panelists reliably preferred NaFeEDTA as the most suitable
      Fe fortificant for dehulled lentils for 5 attributes. Overall, lentil dal
      fortified with NaFeEDTA can offer a simple and low-cost solution to human health
      problems associated with iron-related malnutrition.

PMID- 29469949
TI  - Safety profile of avelumab in patients with advanced solid tumors: A pooled
      analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel
      200 clinical trials.
AB  - BACKGROUND: Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed
      cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are
      linked to the mechanism of action of this therapeutic class and unique from those
      observed with conventional chemotherapy. METHODS: Patients with advanced solid
      tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patients) and
      phase 2 JAVELIN Merkel 200 (88 patients) trials received avelumab, a human anti
      PD-L1 IgG1 antibody at a dose of 10 mg/kg every 2 weeks. Treatment-related AEs
      (TRAEs) were graded using the National Cancer Institute Common Terminology
      Criteria for Adverse Events (version 4.0). In post hoc analyses, immune-related
      AEs (irAEs) were identified via an expanded AE list and medical review, and
      infusion-related reactions (IRRs) occurring <=2 days after infusion and symptoms
      occurring <=1 day after infusion and resolving <=2 days after onset were
      identified based on prespecified Medical Dictionary for Regulatory Activities
      (MedDRA) terms. RESULTS: Of the 1738 patients analyzed, grade >=3 TRAEs occurred
      in 177 (10.2%); the most common were fatigue (17 patients; 1.0%) and IRR (10
      patients; 0.6%). TRAEs led to discontinuation in 107 patients (6.2%) and death in
      4 patients (0.2%). Grade >=3 irAEs occurred in 39 patients (2.2%) and led to
      discontinuation in 34 patients (2.0%). IRRs or related symptoms occurred in 439
      patients (25.3%; grade 3 in 0.5% [9 patients] and grade 4 in 0.2% [3 patients]).
      An IRR occurred at the time of first infusion in 79.5% of 439 patients who had an
      IRR, within the first 4 doses in 98.6% of 439 patients who had an IRR, and led to
      discontinuation in 35 patients (2.0%). CONCLUSIONS: Avelumab generally was found
      to be well tolerated and to have a manageable safety profile. A minority of
      patients experienced grade >=3 TRAEs or irAEs, and discontinuation was uncommon.
      IRRs occurred mainly at the time of first infusion, and repeated events were
      infrequent. Cancer 2018;124:2010-7. (c) 2018 The Authors. Cancer published by
      Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open
      access article under the terms of the Creative Commons Attribution-NonCommercial
      License, which permits use, distribution and reproduction in any medium, provided
      the original work is properly cited and is not used for commercial purposes.

PMID- 29469950
TI  - Stabilization of the Pentazolate Anion in Three Anhydrous and Metal-Free
      Energetic Salts.
AB  - According to previous reports, metal cations or water molecules are necessary for
      the stabilization of pentazolate anion (cyclo-N5- ) at ambient temperature and
      pressure. Seeking a new method to stabilize N5- is a big challenge. In this work,
      three anhydrous, metal-free energetic salts based on cyclo-N5- 3,9-diamino-6,7
      dihydro-5 H-bis([1,2,4]triazolo)[4,3-e:3',4'-g][1,2,4,5] tetrazepine-2,10-diium,
      N-carbamoylguanidinium, and oxalohydrazinium (oxahy+ ) pentazolate were
      synthesized and isolated. All salts were characterized by elemental analysis, IR
      spectroscopy, 1 H, 13 C, and (in some cases) 15 N NMR spectroscopy, thermal
      analysis (TGA and DSC), and single-crystal XRD analysis. Computational studies
      associated with heats of formation and detonation performance were performed by
      using Gaussian 09 and Explo5 programs, respectively. The sensitivity of the salts
      towards impact and friction was determined, and overall the real N5 explosives
      showed promising energetic properties.

PMID- 29469951
TI  - The minimal clinically important difference of the Richmond Agitation-Sedation
      Scale in patients with cancer with agitated delirium.
AB  - BACKGROUND: The Richmond Agitation-Sedation Scale (RASS) is commonly used to
      assess psychomotor activity; however, to the authors' knowledge, its minimal
      clinically important difference (MCID) has not been determined to date. The
      objective of the current study was to identify the MCID for RASS using 2 anchor
      based approaches. METHODS: The current study was a secondary analysis of a
      randomized controlled trial to compare the effect of lorazepam versus placebo as
      an adjuvant to haloperidol for persistent agitation in patients with delirium.
      The primary outcome was change in RASS (10-point numeric rating scale ranging
      from -5 [unarousable] to +4 [combative]) from baseline to 8 hours after treatment
      administration. The sensitivity-specificity and within-patient change methods
      were used to identify the MCID, with the anchor being patient comfort after the
      study intervention as perceived by caregivers and nurses. RESULTS: A total of 90
      patients were randomized and 58 (64%) received the study medication for
      restlessness/agitation (mean baseline RASS, 1.6). A total of 23 caregivers (61%)
      and 23 nurses (55%) perceived that the patient was more comfortable after
      treatment. Using the sensitivity-specificity method, the optimal RASS reduction
      was >=4 points according to both caregivers (sensitivity of 61% and specificity
      of 80%; area under the curve, 0.71) and nurses (sensitivity of 73% and
      specificity of 84%; area under the curve, 0.78). The RASS cutoff value based on
      the within-patient change method was similar (-4.2 for caregivers and -4.0 for
      nurses). CONCLUSIONS: For patients with persistent restlessness/agitation, a
      reduction of >=4 points in RASS was considered to be the MCID for both nurses and
      caregivers. These preliminary findings may have implications for sample size
      calculation and the interpretation of treatment effect in future delirium trials.
      Cancer 2018;124:2246-52. (c) 2018 American Cancer Society.

PMID- 29469952
TI  - Profiling and Imaging of Phospholipids in Brains of Abcd1-Deficient Mice.
AB  - ABCD1 is a gene responsible for X-linked adrenoleukodystrophy (X-ALD), and is
      critical for the transport of very long-chain fatty acids (VLCFA) into
      peroxisomes and subsequent beta-oxidation. VLCFA-containing lipids accumulate in
      X-ALD patients, although the effect of ABCD1-deficiency on each lipid species in
      the central nervous system has not been fully characterized. In this study, each
      phospholipid and lysophospholipid species in Abcd1-deficient mice brains were
      profiled by liquid chromatography-mass spectrometry. Among the phospholipid and
      lysophospholipid species that are significantly more enriched in Abcd1-deficient
      mice brains, VLCFA were present in 75, 15, 5, 4, and 1 species of
      phosphatidylcholine, phosphatidylethanolamine, sphingomyelin,
      lysophosphatidylcholine, and lysophosphatidylethanolamine, respectively. Most
      VLCFA were incorporated at the sn-1 position of phosphatidylcholine and
      phosphatidylethanolamine. Among the phospholipid species that are significantly
      less enriched in Abcd1-deficient mice brains, odd-numbered saturated or mono
      unsaturated fatty acyl moieties are contained in all phosphatidylcholine species.
      In addition, a number of phosphatidylglycerol, phosphatidylinositol, and
      phosphatidylserine species contained highly unsaturated fatty acyl moieties.
      Intriguingly, 44:1 phosphatidylcholine with VLCFA was mainly distributed in the
      gray matter, such as the cortex, but not in the white matter in the cerebrum and
      cerebellum. These results show that ABCD1-deficiency causes metabolic alternation
      of long-chain fatty acids and VLCFA. Moreover, our results imply a molecular
      mechanism for the incorporation of saturated or monounsaturated VLCFA into the sn
      1 position of phospholipids, and also indicate that the distribution of
      phospholipids with VLCFA may correlate with the development of X-ALD.

PMID- 29469953
TI  - Risk stratification using lean body mass in patients undergoing transcatheter
      aortic valve replacement.
AB  - BACKGROUND: The prognostic impact of skeletal muscle mass, assessed using lean
      body mass (LBM), remain unclear in patients who underwent transcatheter aortic
      valve replacement (TAVR). The aim of this study to assess prognostic impact of
      LBM on mortality after TAVR. METHODS: We assessed 1,613 patients (median age 85
      years, 70% female) who underwent TAVI from October 2013 to April 2016 using OCEAN
      (Optimized transCathEter vAlvular interveNtion)-TAVI registry data. LBM was
      calculated using the James formula. The primary endpoint was all-cause death
      after TAVR. RESULTS: Median follow-up period was 287 days (interquartile range
      110-462). The Kaplan-Meier analysis demonstrated that patients with low LBM had
      significantly higher incidence of all-cause death than those with high LBM in
      male (32.3% vs. 9.9%, log rank P < 0.001) and female (15.8% vs. 9.2%, log-rank P
      = 0.011). On contrary, the risk stratification using body mass index (BMI) could
      not validate into female patients who underwent TAVR. The multivariate analysis
      showed that the LBM was an independent predictor of all-cause death in male
      (Hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.89-0.98) and female (HR
      0.94; 95% CI 0.89-0.99). Inversely, the assessment using BMI could not identify
      the high-risk population in a female. CONCLUSIONS: The patients with low LBM had
      the higher incidence of all-cause death after TAVR than those with high LBM,
      regardless of gender. Thus, the risk stratification using LBM might provide
      further insight to identify the high-risk TAVR population, compared to
      conventional risk stratification using BMI.

PMID- 29469954
TI  - Apremilast Alters Behavioral Responses to Ethanol in Mice: II. Increased
      Sedation, Intoxication, and Reduced Acute Functional Tolerance.
AB  - BACKGROUND: In our companion paper, we reported that the phosphodiesterase type 4
      inhibitor apremilast reduced ethanol (EtOH) intake and preference in different
      drinking models in male and female C57BL/6J mice. In this study, we measured the
      effects of apremilast on other behaviors that are correlated with EtOH
      consumption. METHODS: The effects of apremilast (20 mg/kg) on the following
      behaviors were studied in male and female C57BL/6J mice: locomotor response to a
      novel situation; EtOH- and lithium chloride (LiCl)-induced conditioned taste
      aversion (CTA) to saccharin; conditioned place preference (CPP) and conditioned
      place avoidance (CPA) to EtOH; severity of handling-induced convulsions after
      EtOH administration; EtOH-induced anxiolytic-like behavior in the elevated plus
      maze; duration of EtOH-induced loss of righting reflex (LORR); recovery from EtOH
      induced motor impairment on the rotarod; and acute functional tolerance (AFT) to
      EtOH's ataxic effects. RESULTS: Apremilast did not change the acquisition of EtOH
      induced CPP, severity of acute withdrawal from EtOH, or EtOH's anxiolytic-like
      effect. Apremilast did not alter the extinction of EtOH- or LiCl-induced CTA, but
      may interfere with acquisition of CTA to EtOH. Apremilast increased the
      acquisition of CPA to EtOH, reduced locomotor responses to a novel situation, and
      prolonged the duration of LORR and the recovery from acute motor incoordination
      induced by EtOH. The longer recovery from the ataxic effect may be attributed to
      reduced development of AFT to EtOH. CONCLUSIONS: Our results suggest that
      apremilast increases the duration of EtOH intoxication by reducing AFT.
      Apremilast also reduces some aspects of general reward and increases EtOH's
      aversive properties, which might also contribute to its ability to reduce EtOH
      drinking.

PMID- 29469955
TI  - Variability of Symmetric Dimethylarginine in Apparently Healthy Dogs.
AB  - BACKGROUND: Symmetric dimethylarginine (SDMA) is a screening tool for early
      kidney dysfunction and monitoring treatment in cases of chronic kidney disease
      (CKD). There are no current studies describing the suitability of this test for
      use with published population-based reference intervals. HYPOTHESIS/OBJECTIVES:
      To determine the components of biological variability, the index of individuality
      (IOI), the critical difference between sequential measurements (CD ) and the
      number of measurements required to assess the homeostatic set point (HSP), for
      both SDMA and serum creatinine (sCr), in apparently healthy dogs. ANIMALS: Twenty
      apparently healthy adult dogs owned by clients or staff at a veterinary teaching
      hospital. METHODS: Prospective, observational study. Blood was collected from
      each dog on 9 occasions, and SDMA and sCr were measured in duplicate using
      commercially available assays. RESULTS: SDMA and sCr had intermediate and low IOI
      values of 0.87 and 0.28, respectively. The CD of SDMA and sCr, was 1.34 ug/dL and
      0.89 umol/L, respectively. The sample numbers required for estimation of an
      individual's HSP (with 90 and 95% CI) for SDMA and sCr were 8 and 45, and 2 and
      12 sequential measurements, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Based on our findings, in comparison to sCr, SDMA is better suited for use with
      population-based reference intervals. False-negative test results could occur
      when comparing a single test result from an individual to such intervals. Ideally
      CD should be used with sequential measurements.

PMID- 29469956
TI  - IFN-gamma orchestrates tumor elimination, tumor dormancy, tumor escape, and
      progression.
AB  - Tumor immunoediting consisting of three phases of elimination, equilibrium or
      dormancy, and escape has been supported by preclinical and clinical data. A
      comprehensive understanding of the molecular mechanisms by which antitumor immune
      responses regulate these three phases are important for developing highly
      tailored immunotherapeutics that can control cancer. To this end, IFN-gamma
      produced by Th1 cells, cytotoxic T cells, NK cells, and NKT cells is a
      pleiotropic cytokine that is involved in all three phases of tumor immunoediting,
      as well as during inflammation-mediated tumorigenesis processes. This essay
      presents a review of literature and suggests that overcoming tumor escape is
      feasible by driving tumor cells into a state of quiescent but not indolent
      dormancy in order for IFN-gamma-producing tumor-specific T cells to prevent tumor
      relapse.

PMID- 29469957
TI  - The Effect of Urine Concentration and pH on the Growth of Escherichia Coli in
      Canine Urine In Vitro.
AB  - BACKGROUND: Lower urinary tract infections are common in dogs, and Escherichia
      coli is the most common bacterial pathogen isolated. The literature has
      conflicting evidence regarding the inhibitory effects of urine concentration and
      pH on E. coli growth. HYPOTHESIS/OBJECTIVES: To determine the effect of different
      pH and urine concentrations on E. coli growth in vitro. ANIMALS: Voided urine
      samples from 10 apparently healthy spayed female dogs were used. METHODS: A
      matrix of 9 urine specific gravity (USG; 1.010, 1.020, and 1.030) and pH (5.5,
      7.0, and 8.5) combinations was prepared by diluting and titrating filtered voided
      urine samples. Three E. coli isolates were obtained from urine of female dogs
      with signs of lower urinary tract infection and cultured at different urine pH
      and USG combinations in wells of a microtiter plate. The number of E. coli colony
      forming units (CFU) per mL of urine was calculated after aerobic incubation of
      the urine at 37 degrees C for 18 hours, and statistically compared. RESULTS:
      Significant differences were identified in the mean log CFU/mL among different
      combinations of pH and USG. The lowest log CFU/mL were observed in alkaline
      concentrated urine (pH 8.5 and USG 1.030). CONCLUSIONS AND CLINICAL IMPORTANCE:
      Escherichia coli in vitro growth was higher in neutral to acidic and diluted
      urine compared to alkaline and concentrated urine. The impact of non-alkalizing
      diluting diets on the incidence of E. coli lower urinary tract infections should
      be further explored.

PMID- 29469958
TI  - Long-term experience with intranasal bevacizumab therapy.
AB  - OBJECTIVES/HYPOTHESIS: Long-term follow-up of intranasal bevacizumab therapy in
      hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: Prospective,
      noncomparative study. METHODS: Patients treated for HHT-associated epistaxis by
      intranasal submucosal bevacizumab injections between June 2011 and August 2013
      were included and followed prospectively. The effectiveness of the treatment was
      evaluated by the epistaxis severity score (ESS); the epistaxis intensity,
      frequency, and the need of blood transfusion (IFT) score; and hemoglobin levels.
      RESULTS: Thirty-three patients were included. The total number of treatments with
      intranasal bevacizumab injection was 210. The mean number of treatments per
      patient was 6.2 +/- 4.6 (range, 1-16), and the mean treatment and observation
      period was 38.8 +/- 21.8 months (range, 2-66 months). Four patients showed no
      improvement after treatment. Eleven patients (33.3%) showed initial improvement
      in both ESS and IFT, but the treatment was discontinued before the end of the
      study because the effect became gradually shorter lasting despite repeated
      injections. Twelve patients (36.3%) continued to have a positive response to the
      treatment at the end of the study. No local adverse effects were observed, but
      one patient developed osteonecrosis in both knees during the treatment period.
      CONCLUSIONS: Intranasal bevacizumab injection is an effective treatment for most
      of the moderate and severe grades of HHT-associated epistaxis. The duration of
      the effect of the treatment was variable. Primary and late resistance phenomena
      to the treatment were quite common. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2237
      2244, 2018.

PMID- 29469959
TI  - Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2-Keap1 interaction:
      Activation of antioxidative pathway in papillary thyroid carcinoma.
AB  - BACKGROUND: Nuclear factor erythroid 2-like 2 (NFE2L2) encodes Nrf2,
      transcription factor of antioxidative genes. In the presence of reactive oxygen
      species, Keap1 (Kelch-ECH-associating protein-1) inhibitor complex undergoes
      conformational changes disrupting Keap1-Nrf2 binding and Nrf2 translocates into
      nucleus. We evaluated the presence of mutations in NFE2L2 and KEAP1 in papillary
      thyroid carcinomas (PTCs) and correlated them with clinical presentation.
      METHODS: Coding regions of NFE2L2 and KEAP1 were sequenced in 131 patients with
      PTC. Clinical and histopathological features were analyzed. Immunohistochemical
      analysis of Nrf2 expression was performed in mutated carcinomas. RESULTS:
      Although no mutations were found in NFE2L2, missense mutations in KEAP1 were
      observed in 6 patients with PTC (4.6%). Immunohistochemistry showed increased
      Nrf2 expression in nuclei of all mutated carcinomas, which presented poor
      prognostic features in histopathology. CONCLUSION: We identified mutations in
      KEAP1 associated with Nrf2 overexpression in PTC. Mutations favored disruption of
      inhibitory interaction Nrf2-Keap1 to enable increased antioxidant Nrf2 activity,
      possibly with prognostic consequences.

PMID- 29469960
TI  - Ultra-Performance Liquid Chromatography-Mass Spectrometry Analysis of Free and
      Esterified Oxygenated Derivatives from Docosahexaenoic Acid in Rat Brain.
AB  - Docosahexaenoic acid (DHA), a prominent long-chain fatty acid of the omega-3
      family, is present at high amount in brain tissues, especially in membrane
      phospholipids. This polyunsaturated fatty acid is the precursor of various
      oxygenated lipid mediators involved in diverse physiological and
      pathophysiological processes. Characterization of DHA-oxygenated metabolites is
      therefore crucial for better understanding the biological roles of DHA. In this
      study, we identified and measured, by ultrahigh-performance liquid chromatography
      coupled with tandem mass spectrometry, a number of oxygenated products derived
      from DHA in exsanguinated and nonexsanguinated brains. These metabolites were
      found both in free form and esterified in phospholipids. Interestingly, both (R)-
      and (S)-monohydroxylated fatty acid stereoisomers were observed free and
      esterified in phospholipids. Monohydroxylated metabolites were the main
      derivatives; however, measurable amounts of dihydroxylated products such as
      protectin DX were detected. Moreover, exsanguination allowed discriminating brain
      oxygenated metabolites from those generated in blood. These results obtained in
      healthy rats allowed an overview on the brain oxygenated metabolism of DHA, which
      deserves further research in pathophysiological conditions, especially in
      neurodegenerative diseases.

PMID- 29469961
TI  - Relapse and survival after transplantation for complex karyotype acute myeloid
      leukemia: A report from the Acute Leukemia Working Party of the European Society
      for Blood and Marrow Transplantation and the University of Texas MD Anderson
      Cancer Center.
AB  - BACKGROUND: Despite recent advances in allogeneic hematopoietic stem cell
      transplantation (AHSCT), the outcome of patients who have acute myeloid leukemia
      (AML) with a complex karyotype (CK) remains poor. The objective of this study was
      to identify prognostic factors associated with post-transplantation survival in a
      large cohort of patients with CK AML. METHODS: In total, data on 1342
      consecutively patients who underwent transplantation for CK (>=3 chromosomal
      abnormalities) AML were provided by the Acute Leukemia Working Party of the
      European Society for Blood and Marrow Transplantation and from the University of
      Texas MD Anderson Cancer Center database were included in the analysis. The
      median patient age was 52 years. The donors were human leukocyte antigen-matched
      related donors (N = 749), matched unrelated donors (N = 513), and mismatched
      unrelated donors (N = 80). RESULTS: Relapse was the main cause of treatment
      failure. Overall, 51% of patients relapsed, 17.6% died of treatment-related
      mortality, and 31.3% survived leukemia-free. In multivariate analysis, the
      factors associated with an increased risk of relapse were age (>40 years; hazard
      ratio [HR], 1.1 per 10 years; P = .02), secondary AML (HR, 1.35; P = .01), active
      disease at transplantation (HR, 1.98; P < .001), and deletion/monosomy 5 (HR,
      1.5; P < .001); whereas age (HR, 1.15 per 10 years; P < .001), secondary AML (HR,
      1.36; P = .001), active disease at transplantation (HR, 1.99; P < .001),
      deletion/monosomy 5 (HR, 1.24; P = .008), and deletion/monosomy 7 (HR, 1.44; P <
      .001) predicted for leukemia-free survival. CONCLUSIONS: Disease relapse remains
      the most common cause of treatment failure for patients with CK AML after
      transplantation. Novel approaches to decrease the relapse rate and improve
      survival are needed in these patients. Cancer 2018;124:2134-41. (c) 2018 American
      Cancer Society.

PMID- 29469963
TI  - Electron Transfer around a Molecular Corner.
AB  - The distance dependence of electron transfer (ET) is commonly investigated in
      linear rigid rod-like compounds, but studies of molecular wires with integrated
      corners imposing 90 degrees  angles are very rare. By using spirobifluorene as a
      key bridging element and by substituting it at different positions, two isomeric
      series of donor-bridge-acceptor compounds with either nearly linear or angled
      geometries were obtained. Photoinduced ET in both series is dominated by rapid
      through-bond hole hopping across oligofluorene bridges over distances of up to 70
      A. Despite considerable conformational flexibility, direct through-space and
      through-solvent ET is negligible even in the angled series. The independence of
      the ET rate constant on the total number of fluorene units in the angled series
      is attributed to a rate-limiting tunneling step through the spirobifluorene
      corner. This finding is relevant for multidimensional ET systems and grids in
      which individual molecular wires are interlinked at 90 degrees  angles.

PMID- 29469962
TI  - Apremilast Alters Behavioral Responses to Ethanol in Mice: I. Reduced Consumption
      and Preference.
AB  - BACKGROUND: Phosphodiesterase type 4 (PDE4) inhibitors produce widespread anti
      inflammatory effects and reduce ethanol (EtOH) consumption in several rodent
      models. These drugs are potential treatments for several diseases, including
      central nervous system disorders, but clinical use is limited by their emetic
      activity. Apremilast is a selective PDE4 inhibitor with fewer gastrointestinal
      side effects that is FDA-approved for the treatment of psoriasis. METHODS: We
      measured the acute and chronic effects of apremilast on EtOH consumption in male
      and female C57BL/6J mice using the continuous and intermittent 24-hour 2-bottle
      choice drinking models. We also studied the effects of apremilast on preference
      for sucrose or saccharin, spontaneous locomotor activity, and blood EtOH
      clearance. Finally, apremilast levels in plasma, liver, and brain were measured 1
      or 2 hours after injection. RESULTS: In the continuous and intermittent drinking
      tests, apremilast (15 to 50 mg/kg, p.o.) dose dependently reduced EtOH intake and
      preference in male and female mice. Higher doses of apremilast (30 to 50 mg/kg)
      also reduced total fluid intake in these mice. Chronic administration of
      apremilast (20 mg/kg) produced a stable reduction in EtOH consumption in both
      drinking tests with no effect on total fluid intake. The drinking effects were
      reversible after drug treatment was replaced with vehicle administration (saline)
      for 2 to 4 days. Six daily apremilast injections did not alter preference for
      saccharin or sucrose in male or female mice. Apremilast (20 mg/kg) transiently
      decreased spontaneous locomotor activity and did not alter blood EtOH clearance.
      The highest levels of apremilast were found in liver followed by plasma and
      brain. CONCLUSIONS: Apremilast produced stable reductions in voluntary EtOH
      consumption and was rapidly distributed to plasma and tissues (including the
      brain), suggesting that it may be an improved PDE4 inhibitor for medication
      development and repurposing efforts to treat alcohol abuse.

PMID- 29469964
TI  - Impact of SLCO1B1 Genotype on Pediatric Simvastatin Acid Pharmacokinetics.
AB  - This study investigated the impact of allelic variation in SLCO1B1, a gene
      encoding for the liver-specific solute carrier organic anion transporter family
      member 1B1 protein (SLCO1B1), on simvastatin and simvastatin acid (SVA) systemic
      exposure in children and adolescents. Participants (8-20 years old) with at least
      1 variant SLCO1B1 c.521T>C allele (521TC, n = 15; 521CC, n = 2) and 2 wild-type
      alleles (521TT, n = 15) completed a single oral dose pharmacokinetic study. At
      equivalent doses, SVA exposure was 6.3- and 2.5-fold greater in 521CC and TC
      genotypes relative to 521TT (Cmax , 2.1 +/- 0.2 vs 1.0 +/- 0.5 vs 0.4 +/- 0.3
      ng/mL; P < .0001; and AUC, 12.1 +/- 0.3 vs 4.5 +/- 2.5 vs 1.9 +/- 1.8 ng.h/mL; P
      < .0001). The impact of the SLCO1B1 c.521 genotype was more pronounced in
      children, although considerable interindividual variability in SVA exposure was
      observed within genotype groups. In addition, SVA systemic exposure was
      negligible in 25% of pediatric participants. Further investigation of the
      ontogeny and genetic variation of SVA formation and SLCO1B1-mediated hepatic
      uptake is necessary to better understand the variability in SVA exposure in
      children and its clinical consequences.

PMID- 29469966
TI  - The effect of skin surface topography and skin colouration cues on perception of
      male facial age, health and attractiveness.
AB  - OBJECTIVE: Previous studies investigating the effects of skin surface topography
      and colouration cues on the perception of female faces reported a differential
      weighting for the perception of skin topography and colour evenness, where
      topography was a stronger visual cue for the perception of age, whereas skin
      colour evenness was a stronger visual cue for the perception of health. We extend
      these findings in a study of the effect of skin surface topography and colour
      evenness cues on the perceptions of facial age, health and attractiveness in
      males. METHODS: Facial images of six men (aged 40 to 70 years), selected for co
      expression of lines/wrinkles and discolouration, were manipulated digitally to
      create eight stimuli, namely, separate removal of these two features (a) on the
      forehead, (b) in the periorbital area, (c) on the cheeks and (d) across the
      entire face. Omnibus (within-face) pairwise combinations, including the original
      (unmodified) face, were presented to a total of 240 male and female judges, who
      selected the face they considered younger, healthier and more attractive.
      RESULTS: Significant effects were detected for facial image choice, in response
      to skin feature manipulation. The combined removal of skin surface topography
      resulted in younger age perception compared with that seen with the removal of
      skin colouration cues, whereas the opposite pattern was found for health
      preference. No difference was detected for the perception of attractiveness.
      These perceptual effects were seen particularly on the forehead and cheeks.
      Removing skin topography cues (but not discolouration) in the periorbital area
      resulted in higher preferences for all three attributes. CONCLUSION: Skin surface
      topography and colouration cues affect the perception of age, health and
      attractiveness in men's faces. The combined removal of these features on the
      forehead, cheeks and in the periorbital area results in the most positive
      assessments.

PMID- 29469965
TI  - Vitamin D Receptor Expression in Dogs.
AB  - BACKGROUND: There is growing evidence linking low blood vitamin D concentration
      to numerous diseases in people and in dogs. Vitamin D influences cellular
      function by signaling through the vitamin D receptor (VDR). Little is known about
      which non-skeletal tissues express the VDR or how inflammation influences its
      expression in the dog. OBJECTIVES: To define which non-skeletal canine tissues
      express the VDR and to investigate expression in inflamed small intestine.
      ANIMALS: Thirteen non-skeletal tissues were collected prospectively from 6
      control dogs. Thirty-five dogs diagnosed with a chronic enteropathy (CE) and 24
      control dogs were prospectively enrolled and duodenal biopsies were evaluated for
      VDR expression. METHODS: Prospective; blinded assessment of canine intestinal
      VDR. Dogs with CE were included once other identifiable causes of intestinal
      disease were excluded. Age matched controls were included with no intestinal
      clinical signs. VDR expression was assessed immunohistochemically in all samples,
      using a Rat IgG VDR monoclonal antibody. Quantitative real-time polymerase chain
      reaction (qPCR) was also used for duodenal biopsies. RESULTS: VDR expression as
      assessed by immunohistochemistry (IHC) was highest in the kidney, duodenum, skin,
      ileum and spleen, and weak in the colon, heart, lymph node, liver, lung, and
      ovary. Gastric and testicular tissue did not express the VDR. There was no
      statistical difference in duodenal VDR expression between the 24 healthy dogs and
      34 dogs with CE when quantified by either qPCR (P = 0.87) or IHC (P = 0.099).
      CONCLUSIONS AND CLINICAL IMPORTANCE: The lack of down regulation of VDR
      expression in inflamed intestine contrasts with previous studies in humans. Our
      findings support future studies to investigate whether vitamin D and its
      analogues can be used to modulate intestinal inflammation in the dog.

PMID- 29469968
TI  - First follow-up of a breakable stent for implantation in infants dedicated for a
      life-long stay.
AB  - OBJECTIVE AND METHODS: The use of conventional metal stents in infants is
      severely limited by subsequent somatic growth. The use of a breakable balloon
      expandable stent (BS) designed for initial implant at small diameters but with
      properties that allow unlimited dilation in line with growth has potential
      advantages in this patient group. This study reports our experience with this
      stent between 2010 and 2014. A total of 17 BS were implanted in 14 infants (mean
      age 4.8 months). All but one stent was placed into the aorta to treat
      coarctation. RESULTS: All implantations were successful and initial gradients
      dropped from a mean of 25-6 mm Hg (range from 1-50 down to 0-24 mm Hg). Mean
      follow-up was 3.3 years (range 5 days to 7 years) with a total cumulative follow
      up of 46.7 patient years. Stent redilation was performed a median of 2.5 times
      (range 0-5). Sixteen stents in 13 patients remain in place. Following redilation
      beyond 10 mm, circumferential integrity of the BS was lost in 10 patients. No
      further stent implantation or related surgery was necessary. A 3 mm dissection
      occurred in one patient after redilation. CONCLUSIONS: The BS performed well in
      terms of relief of stenosis and could be successfully dilated during the phase of
      the infants' most rapid growth. Mild intimal proliferation occurred in some
      patients early after implantation. In the course of the stepwise redilations and
      growth adjustments, both, planned longitudinal and transverse fractures occurred
      without allowing a collapse of the stented area.

PMID- 29469967
TI  - Biotransformation of 4-fluoro-N-(1-{2-[(propan-2-yl)phenoxy]ethyl}-8
      azabicyclo[3.2.1]octan-3-yl)-benzenesulfonamide, a novel potent 5-HT7 receptor
      antagonist with antidepressant-like and anxiolytic properties: In vitro and in
      silico approach.
AB  - The aim of the study was to investigate the metabolism of 4-fluoro-N-(1-{2
      [(propan-2-yl)phenoxy]ethyl}-8-azabicyclo[3.2.1]octan-3-yl)-benzenesulfonamide
      (PZ-1150), a novel 5-HT7 receptor antagonist with antidepressant-like and
      anxiolytic properties, by the following three ways: in vitro with microsomes; in
      vitro employing Cunninghamella echinulata, and in silico using MetaSite.
      Biotransformation of PZ-1150 with microsomes resulted in five metabolites, while
      transformation with C. echinulata afforded two metabolites. In both models, the
      predominant metabolite occurred due to hydroxylation of benzene ring. In silico
      data coincide with in vitro experiments, as three MetaSite metabolites matched
      compounds identified in microsomal samples. In human liver microsomes PZ-1150
      exhibited in vitro half-life of 64 min, with microsomal intrinsic clearance of
      54.1 MUL/min/mg and intrinsic clearance of 48.7 mL/min/kg. Therefore, PZ-1150 is
      predicted to be a high-clearance agent. The study demonstrated the applicability
      of using microsomal model coupled with microbial model to elucidate the metabolic
      pathways of compounds and comparison with in silico metabolite predictions.

PMID- 29469969
TI  - Nanobody-Enabled Reverse Pharmacology on G-Protein-Coupled Receptors.
AB  - The conformational complexity of transmembrane signaling of G-protein-coupled
      receptors (GPCRs) is a central hurdle for the design of screens for receptor
      agonists. In their basal states, GPCRs have lower affinities for agonists
      compared to their G-protein-bound active state conformations. Moreover, different
      agonists can stabilize distinct active receptor conformations and do not
      uniformly activate all cellular signaling pathways linked to a given receptor
      (agonist bias). Comparative fragment screens were performed on a beta2 
      adrenoreceptor-nanobody fusion locked in its active-state conformation by a G
      protein-mimicking nanobody, and the same receptor in its basal-state
      conformation. This simple biophysical assay allowed the identification and
      ranking of multiple novel agonists and permitted classification of the efficacy
      of each hit in agonist, antagonist, or inverse agonist categories, thereby
      opening doors to nanobody-enabled reverse pharmacology.

PMID- 29469970
TI  - Glimepiride treatment in a patient with type A insulin resistance syndrome due to
      a novel heterozygous missense mutation in the insulin receptor gene.
AB  - AIMS/INTRODUCTION: Glimepiride is a sulfonylurea known to have unique insulin
      mimetic and sensitizing effects. We aimed to study the efficacy of glimepiride in
      a patient with type A insulin resistance syndrome. MATERIALS AND METHODS: A 15
      year-old girl with type A insulin resistance syndrome was treated with glimpiride
      for 6 months. Self-monitoring of blood glucose was recorded, and oral glucose
      tolerance tests on glucose and insulin were measured during the treatment.
      Hyperinsulinemic euglycemic clamp was used to evaluate whole-body insulin
      sensitivity before and after the treatment. RESULTS: A novel heterozygous
      missense mutation at exon 19 (c.3427A>T) in the tyrosine kinase domain of the
      INSR gene was identified, causing an amino acid replacement of phenylalanine for
      isoleucine at codon 1143 (Ile1143Phe). Before the treatment, the patient's
      glycated hemoglobin was 7.0%, plasma glucose during oral glucose tolerance test
      was 6.7, 12.8 and 17.3 mmol/L, and simultaneous serum insulin was 80.7, 137.5 and
      >300 MUU/mL. There were no significant differences between self-monitored blood
      glucose measured at each time-point among different glimepiride dosages, or
      during the 14 weeks when glimepiride was used at its maximal dosage (6 mg/day).
      Oral glucose tolerance test showed little change in plasma glucose and serum
      insulin. Glycated hemoglobin decreased by 0.8% after the treatment. However, a
      euglycemic clamp study showed that the M value decreased from 5.25 to 2.90
      mg/kg/min, showing increased insulin resistance. CONCLUSIONS: Treatment with
      glimepiride did not improve insulin sensitivity in a patient with type A insulin
      resistance syndrome carrying Ile1143Phe heterozygous mutation in the INSR gene.
      Large-scale long-term studies assembled worldwide are required to optimize
      treatment algorithms for patients with type A insulin resistance syndrome.

PMID- 29469973
TI  - Comment on the article "TFM classification and staging of oral submucous
      fibrosis: A new proposal".

PMID- 29469972
TI  - Cooling of the oral mucosa to prevent adverse effects of chemotherapeutic agents:
      An in vitro study.
AB  - BACKGROUND: The cytotoxic effect of chemotherapeutic agents to the oral mucosa,
      as a side effect of cancer treatment, is a major problem. Cooling the oral mucosa
      using ice chips in conjunction with chemotherapy is known to reduce the severity
      of oral mucositis. However, although the use of ice chips is of clinical value,
      this method of cooling has inherent problems including discomfort for the
      patient, non-uniformity and fluctuations in cooling temperature throughout the
      oral cavity. Furthermore, despite being used clinically, it is not known what
      reduction in temperature is required to prevent oral mucositis. The aim of this
      study was therefore to determine in vitro if the cytotoxic effect of 5
      fluorouracil (5-FU) on the oral mucosa could be reduced by lowering the
      temperature during chemotherapeutic treatment. METHODS: Tissue-engineered oral
      mucosal (TEOM) models were incubated at 20, 25, 30 or 35 degrees C for 30 minutes
      followed by exposure to a clinically relevant concentration of 5-FU (162 MUg/mL)
      for 2 hours and compared with untreated models (35 degrees C). Cell viability and
      inflammatory cytokine production (IL-6 and TNF-alpha) were measured using
      PrestoBlue(r) and ELISA, respectively. RESULTS: TEOM models incubated at 20
      degrees C showed an increased cell viability and had a reduced IL-6 and TNF-alpha
      production compared to models treated with 5-FU incubated at 35 degrees C.
      CONCLUSION: This study demonstrates a reduced cytotoxic effect to the TEOM by
      reducing the temperature of the tissue during chemotherapy treatment and suggests
      that decreasing the temperature to 20 degrees C could have clinical advantages.

PMID- 29469974
TI  - Assessment of Canine Pancreas-Specific Lipase and Outcomes in Dogs with
      Hemodialysis-Dependent Acute Kidney Injury.
AB  - BACKGROUND: Renal replacement therapies can be life-saving for dogs with severe
      acute kidney injury (AKI), however, comorbidities including pancreatitis might
      affect outcome. HYPOTHESIS/OBJECTIVES: To investigate the prevalence of pancreas
      specific lipase (Spec cPL) measurements consistent with pancreatitis (>=400
      MUg/L) in dogs undergoing intermittent hemodialysis (IHD) for treatment of AKI
      and to determine whether there were associations between 30-days outcomes and
      Spec cPL measurements. ANIMALS: Fifty-three client-owned dogs presented to
      teaching hospitals between November 2008 and September 2016 that underwent IHD.
      METHODS: Retrospective medical record review from dogs that received IHD for
      management of AKI and also had a Spec cPL measurement. Association between
      survival, dialysis-dependency, and Spec cPL measurements was assessed. RESULTS:
      Forty of 53 (76%) dogs were alive at 30-days and 33/53(62%) had a Spec cPL result
      >=400 MUg/L. Spec cPL was not significantly different either between surviving
      (635.5 MUg/L, range 29-1,001) and nonsurviving dogs (860 MUg/L, range 56-1,001; P
      = 0.75) or between dialysis-dependent (1,001 MUg/L, range 177-1,001) and
      nondialysis-dependent dogs (520 MUg/L, range 29-1,001; P = 0.08). Spec cPL >=400
      MUg/L was not significantly associated either with survival (P = 0.74) or
      dialysis-dependency (P = 0.33). CONCLUSIONS AND CLINICAL IMPORTANCE: Results
      revealed a high prevalence of Spec cPL >=400 MUg/L in dogs with AKI treated with
      IHD. No significant associations between Spec cPL and survival or dialysis
      dependency in dogs with AKI at 30 days were identified in the current study,
      however, the latter could be due to lack of power in this study.

PMID- 29469975
TI  - Biological activities of 3,4,5-trihydroxypiperidines and their N- and O
      derivatives.
AB  - 3,4,5-Trihydroxypiperidines belong to the family of 1,5-dideoxy-1,5-iminosugar
      natural products and are structural analogues of pentose monosaccharides in the
      pyranose form. The biological activities of these apparently structurally simple
      molecules and their N- and O-alkylated and -arylated derivatives are no less
      remarkable than their C-6 hydroxymethyl counterparts of the hexoses (such as 1
      deoxynojirimycin, DNJ). Their biological profiles indicate that the hydroxymethyl
      branch is crucial to neither potency nor selectivity, with O-alkylation
      demonstrated to produce exquisite selectivity extending beyond glycosidase
      inhibition, to immunosuppressant and antibacterial activities.

PMID- 29469977
TI  - Vibrio cholerae cytolysin: Multiple facets of the membrane interaction mechanism
      of a beta-barrel pore-forming toxin.
AB  - Vibrio cholerae cytolysin (VCC) is a membrane-damaging protein toxin with potent
      cytolytic/cytotoxic activity against wide range of eukaryotic cells. VCC is a
      beta-barrel pore-forming toxin (beta-PFT), and it inflicts damage to the target
      cell membranes by forming transmembrane heptameric beta-barrel pores. To exert
      pore-forming activity, VCC must bind to the cell membranes in an efficient
      manner. Efficient interaction with the cell membranes is an essential pre
      requisite to trigger subsequent structural/conformational and organizational
      changes in the toxin molecules leading toward formation of the transmembrane
      oligomeric beta-barrel pores. Based on the large numbers of studies investigating
      the mode of action of VCC, it is now evident that VCC is capable of using
      multiple distinct mechanisms to recognize and bind to the membrane components and
      cell surface molecules. In this review article, we present an overview of our
      current understanding regarding the membrane interaction mechanisms of VCC, and
      their functional implications for the pore-forming activity of the toxin. (c)
      2018 IUBMB Life, 70(4):260-266, 2018.

PMID- 29469976
TI  - Calcitonin Response to Naturally Occurring Ionized Hypercalcemia in Cats with
      Chronic Kidney Disease.
AB  - BACKGROUND: Hypercalcemia is commonly associated with chronic kidney disease
      (CKD) in cats. OBJECTIVES: To explore the calcitonin response to naturally
      occurring ionized hypercalcemia in cats with azotemic CKD, and to assess the
      relationship of plasma calcitonin with ionized calcium, alkaline phosphatase
      (ALP), and urinary calcium excretion. ANIMALS: Thirty-three client-owned cats
      with azotemic CKD and ionized hypercalcemia from first opinion practice. METHODS:
      Cohort study. Calcitonin was measured with an immunoradiometric assay in
      heparinized plasma. Simple correlations were assessed with Kendall's rank
      correlation, and the within-subject correlations of calcitonin with ionized
      calcium and other clinicopathological variables were calculated with a bivariate
      linear mixed effects model. RESULTS: Calcitonin concentrations above the lower
      limit of detection (>1.2 pg/mL; range, 1.7-87.2 pg/mL) were observed in 11 of 33
      hypercalcemic cats (responders). Blood ionized calcium concentration did not
      differ significantly between responders (median, 1.59 [1.46, 1.66] mmol/L) and
      nonresponders (median, 1.48 [1.43, 1.65] mmol/L; P = 0.22). No evidence was found
      for calcitonin and ionized calcium to correlate between cats (taub  = 0.14; P =
      0.31; n = 33), but significant positive correlation was evident within individual
      responders over time (within-subject correlation coefficient [rwithin ], 0.83;
      95% confidence interval [CI], 0.63-0.92). Calcitonin correlated negatively over
      time with plasma ALP (rwithin , -0.55; 95% CI, -0.79 to -0.16). CONCLUSIONS AND
      CLINICAL IMPORTANCE: Calcitonin does not appear to have an important role in
      calcium metabolism in cats with CKD.

PMID- 29469978
TI  - Survey of Equine Referring Veterinarians' Satisfaction with Their Most Recent
      Equine Referral Experience.
AB  - BACKGROUND: Little is known about the veterinary referral process and factors
      that contribute to positive outcomes. OBJECTIVE: To investigate equine referring
      veterinarians' (rDVMs') satisfaction with their most recent referral experience
      and compare rDVM and specialist perspectives. SAMPLE: 187 rDVMs and 92
      specialists (referral care providers). METHODS: Cross-sectional observational
      study. An online survey was administered to both rDVMs and specialists. Referring
      veterinarian satisfaction with their most recent referral experience was
      evaluated. Both rDVMs and specialists were asked to identify factors influencing
      a rDVM's decision where to refer, and the top 3 factors they perceive are
      barriers to referral care. RESULTS: Median rDVM satisfaction with their most
      recent referral care experience was 80 of 100 (mean, 75; range, 8-100). Referring
      veterinarians provided the lowest satisfaction score for the item asking about
      "The competition the referral hospital poses to your practice" (mean, 56.96;
      median, 62; range, 0-100). The top factor rDVMs identified as influencing their
      decision where to refer was "quality of care," whereas specialists identified
      "quality of communication and updates from the clinician." Referring
      veterinarians' top barrier to referral care was "high cost of referral care," and
      for specialists was "poor service provided to the client by the referral
      hospital." CONCLUSIONS AND CLINICAL IMPORTANCE: Referring veterinarians generally
      were satisfied with referral care, but areas exist where rDVMs and specialists
      differ in what they view as important to the referral process. Exploring
      opportunities to overcome these differences is likely to support high quality
      care.

PMID- 29469979
TI  - Clinicians' perspective on an app for patient self-monitoring in eating disorder
      treatment.
AB  - OBJECTIVE: The Recovery Record smartphone app is a self-monitoring tool for
      individuals recovering from eating disorders. Oppositely to traditional pen-and
      paper meal diaries, the app allows for in-app patient-clinician linkage enabling
      clinicians to access patient app data anytime. The aim of our study was to
      explore the interdisciplinary clinical perspective on Recovery Record and its
      impact on treatment. METHOD: Thirty-one clinicians from a Danish eating disorder
      treatment facility participated in field studies and 23 of these in interviews.
      Data were generated and analyzed concurrently applying the inductive methodology
      of Interpretive Description. RESULTS: We found two overarching themes: "Access to
      app data between treatment sessions", and "The patient-clinician relationship".
      Sub-themes associated with the former were "Online obligations" in relation to
      the added workload of continuously monitoring patient app data, and "Prepared or
      prejudiced" relating to advantages and disadvantages of using patient app data as
      preparation for treatment sessions. Sub-themes pertaining to the latter were
      "Expectation discrepancy" in relation to patients' and clinicians' divergent
      expectations for app usage, and "Pacified patients" regarding the clinicians'
      experience that the app potentially compromised the patient initiative in
      treatment sessions. DISCUSSION: Recovery Record induced new and affected pre
      existing treatment and work conditions for clinicians. Clinicians were
      preoccupied with challenges associated with the app, for example, an added work
      load and potential harm to the patient-clinician collaboration. Thus, prior to
      adopting the app, we encourage clinicians and managements to discuss the
      objectives, advantages and disadvantages of adopting the app, and outline
      specific guidelines for patient and clinician app usage.

PMID- 29469980
TI  - Discovery of thiophene-containing biaryl amide derivatives as novel glucagon
      receptor antagonists.
AB  - A novel series of thiophene-containing biaryl amide glucagon receptor (GCGR)
      antagonists were designed and synthesized. Two compounds of this series, 14f and
      14h, exhibited good GCGR binding (IC50  = 6.1 and 4.4 MUm, respectively) and cAMP
      functional activities (IC50  = 4.4 and 14.4 MUm, respectively). The possible
      binding modes of compounds 14f and 14h with GCGR were explored by molecular
      simulation.

PMID- 29469981
TI  - Moisture availability limits subalpine tree establishment.
AB  - In the absence of broad-scale disturbance, many temperate coniferous forests
      experience successful seedling establishment only when abundant seed production
      coincides with favorable climate. Identifying the frequency of past establishment
      events and the climate conditions favorable for seedling establishment is
      essential to understanding how climate warming could affect the frequency of
      future tree establishment events and therefore future forest composition or even
      persistence of a forest cover. In the southern Rocky Mountains, USA, research on
      the sensitivity of establishment of Engelmann spruce (Picea engelmannii) and
      subalpine fir (Abies lasiocarpa)-two widely distributed, co-occurring conifers in
      North America-to climate variability has focused on the alpine treeline ecotone,
      leaving uncertainty about the sensitivity of these species across much of their
      elevation distribution. We compared annual germination dates for >450 Engelmann
      spruce and >500 subalpine fir seedlings collected across a complex topographic
      moisture gradient to climate variability in the Colorado Front Range. We found
      that Engelmann spruce and subalpine fir established episodically with strong
      synchrony in establishment events across the study area. Broad-scale
      establishment events occurred in years of high soil moisture availability, which
      were characterized by above-average snowpack and/or cool and wet summer climatic
      conditions. In the recent half of the study period (1975-2010), a decrease in the
      number of fir and spruce establishment events across their distribution coincided
      with declining snowpack and a multi-decadal trend of rising summer temperature
      and increasing moisture deficits. Counter to expected and observed increases in
      tree establishment with climate warming in maritime subalpine forests, our
      results show that recruitment declines will likely occur across the core of
      moisture-limited subalpine tree ranges as warming drives increased moisture
      deficits.

PMID- 29469982
TI  - Prophylactic administration of carnosine and melatonin abates the incidence of
      renal toxicity induced by an over dose of titanium dioxide nanoparticles.
AB  - The alleviative effects of two antioxidants, carnosine (Car) and melatonin (Mel),
      against titanium dioxide nanoparticles (TiO2 -NPs) toxicity-induced oxidative and
      inflammatory renal damage were examined in rats. Administration of these
      antioxidants along with TiO2 -NPs effectively reduced serum urea, uric acid,
      creatinine, glucose, tumor necrosis factor-alpha, interleukin-6, C-reactive
      protein, immunoglobulin G, vascular endothelial growth factor, and nitric oxide,
      as well as a significant amelioration of the decrease in glutathione levels in
      renal tissue was observed, compared to those in rats treated with TiO2 -NPs
      alone. The renoprotective properties of the antioxidants were confirmed by
      reduced intensity of renal damage as demonstrated by histological findings. In
      conclusion, Car and Mel play protective roles against TiO2 -NPs-induced renal
      inflammation and oxidative injury, likely due to their antioxidant and anti
      inflammatory properties.

PMID- 29469983
TI  - Identification of 4-aryl-1H-pyrrole[2,3-b]pyridine derivatives for the
      development of new B-Raf inhibitors.
AB  - During the last years, a significant interest in the identification of new
      classes of B-Raf inhibitors has emerged. In this study, which was conceived
      within an effort that culminated in the recent report of the first dual
      inhibitors of B-Raf and Hsp90, we describe the identification of four compounds
      based on 4-aryl-1H-pyrrole[2,3-b]pyridine scaffold as interesting starting points
      for the development of new B-Raf inhibitors. Structure-activity relationships and
      predicted binding modes are discussed. Moreover, the novelty of the newly
      identified structures with respect to currently known B-Raf inhibitors was
      assessed through a ligand-based dissimilarity assessment. Finally, structural
      modifications with the potential ability to improve the activity toward B-Raf are
      put forward.

PMID- 29469984
TI  - Coil embolization to successfully treat annular rupture during transcatheter
      aortic valve replacement.
AB  - Aortic annular rupture is one of the most feared complications of transcatheter
      aortic valve replacement (TAVR). This complication often presents as sudden
      cardiac tamponade with hypotension and requires urgent intervention. The
      traditional rescue strategy for such cases is emergency surgical intervention,
      yet the mortality remains high considering most patients who undergo TAVR are not
      candidates for open heart surgery. As such, there is a need for percutaneous
      alternatives to treat this critical complication. Here, we describe a case of
      annular rupture during TAVR that was successfully treated with coil embolization
      at the rupture site. This case illustrates the use of coil embolization as a
      treatment strategy in patients with acute aortic annular rupture who are at high
      risk for surgical intervention.

PMID- 29469985
TI  - Bis-2(5H)-furanone derivatives as new anticancer agents: Design, synthesis,
      biological evaluation, and mechanism studies.
AB  - New bis-2(5H)-furanone derivatives containing a benzidine core were synthesized
      via a one-step transition-metal-free reaction of benzidine with 5-substituted 3,4
      dihalo-2(5H)-furanones. Their antitumor activities against various tumor cells
      have been evaluated by MTT assay. Among them, compound 4e exhibits significant
      inhibitory activity against C6 glioma cells with an IC50 value of 12.1 MUm and
      low toxicity toward HaCaT human normal cells. Studies on the antitumor mechanism
      reveal that cell cycle arrest at S-phase in C6 cells is induced by compound 4e.
      Furthermore, investigations with electronic, fluorescence emission and circular
      dichroism spectra show that compound 4e can significantly interact with C6-DNA.
      These data indicate that DNA may be one of the potential targets for bis-2(5H)
      furanone derivatives as anticancer drugs.

PMID- 29469987
TI  - Magnetic Reduced Graphene Oxide/Nickel/Platinum Nanoparticles Micromotors for
      Mycotoxin Analysis.
AB  - Magnetic reduced graphene oxide/nickel/platinum nanoparticles (rGO/Ni/PtNPs)
      micromotors for mycotoxin analysis in food samples were developed for food-safety
      diagnosis. While the utilization of self-propelled micromotors in bioassays has
      led to a fundamentally new approach, mainly due to the greatly enhanced target
      receptor contacts owing to their continuous movement around the sample and the
      associated mixing effect, herein the magnetic properties of rGO/Ni/PtNPs
      micromotors for mycotoxin analysis are additionally explored. The micromotor
      based strategy for targeted mycotoxin biosensing focused on the accurate control
      of micromotor-based operations: 1) on-the-move capture of free aptamers by
      exploiting the adsorption (outer rGO layer) and catalytic (inner PtNPs layer)
      properties and 2) micromotor stopped flow in just 2 min by exploiting the
      magnetic properties (intermediate Ni layer). This strategy allowed fumonisin B1
      determination with high sensitivity (limit of detection: 0.70 ng mL-1 ) and
      excellent accuracy (error: 0.05 % in certified reference material and
      quantitative recoveries of 104+/-4 % in beer) even in the presence of concurrent
      ochratoxin A (105-108+/-8 % in wines). These results confirm the developed
      approach as an innovative and reliable analytical tool for food-safety
      monitoring, and confirm the role of micromotors as a new paradigm in analytical
      chemistry.

PMID- 29469988
TI  - Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis
      2.
AB  - Schwannomatosis and neurofibromatosis type 2 are hereditary tumor syndromes, and
      peripheral neuropathy has been reported in both. We prospectively applied in vivo
      morphometric measurement of dorsal root ganglia volume in 16 schwannomatosis
      patients, 14 neurofibromatosis type 2 patients, and 26 healthy controls by
      magnetic resonance neurography. Compared to healthy controls, dorsal root ganglia
      hypertrophy was a consistent finding in neurofibromatosis type 2 (L3, + 267%; L4,
      + 235%; L5, + 241%; S1, + 300%; S2, + 242%; Bonferroni-adjusted p < 0.001) but
      not in schwannomatosis. Dorsal root ganglia may be a vulnerable site in
      origination of areflexia and sensory loss and a useful diagnostic marker in
      neurofibromatosis type 2. Ann Neurol 2018;83:854-857.

PMID- 29469986
TI  - Prevalence and duration of breast milk feeding in very preterm infants: A 3-year
      follow-up study and a systematic literature review.
AB  - BACKGROUND: The World Health Organization recommends exclusive breast milk
      feeding until 6 months and continuing up to 2 years of age; little is known about
      whether very preterm infants are fed in accordance with these recommendations. We
      aimed to describe the prevalence and duration of breast milk feeding in very
      preterm children and to systematically review internationally published data.
      METHODS: We evaluated breast milk feeding initiation and duration in very preterm
      children born in 2 Portuguese regions (2011-2012) enrolled in the EPICE cohort
      and followed-up to the age of 3 (n = 466). We searched PubMed(r) from inception
      to January 2017 to identify original studies reporting the prevalence and/or
      duration of breast milk feeding in very preterm children. RESULTS: 91.0% of
      children received some breast milk feeding and 65.3% were exclusively breast fed
      with a median duration of 2 months for exclusive and 3 months for any breast
      milk; only 9.9% received exclusive breast milk for at least 6 months, 10.2%
      received any breast milk for 12 months or more, and 2.0% for up to 24 months. The
      literature review identified few studies on feeding after hospital discharge (n =
      9); these also reported a low prevalence of exclusive breast milk feeding at 6
      months (1.0% to 27.0%) and of any breast milk at 12 months (8.0% to 12.0%).
      CONCLUSIONS: The duration of breast milk feeding among Portuguese very preterm
      infants was shorter than recommended. However, this appears to be common
      globally. Research is needed to inform strategies to promote continued breast
      milk feeding.

PMID- 29469990
TI  - Differential Metabolic Pathway Analysis of the Proteomes of Leishmania donovani
      and Leptomonas seymouri.
AB  - PURPOSE: Although in trypanosomatids, monoxeny (Leptomonas) is ancestral to
      dixeny (Leishmania), however clinical cases of visceral leishmanisis with
      Leptomonas co-infection are increasingly being reported from India. Using a
      proteogenomic approach, a detailed proteome analysis of these two kinetoplastid
      parasites viz., Leishmania and its sister Leptomonas, to catalog the key proteins
      associated with and therefore possibly responsible for phenotype changes in
      Leptomonas evolution and domestication as co-infection with Leishmania is carried
      out. EXPERIMENTAL DESIGN: LC-MS/MS is utilized for this proteomic purpose. One
      Leishmania donovani WHO reference strain and two Leptomonas seymouri isolates,
      which are originally isolated from clinical cases of kala azar patients with
      different inherent drug sensitivity viz., responsive and unresponsive, are used
      in this study. RESULTS: A network analysis, leveraging protein-protein
      interaction data helped to find the roles of the proteins in carbon metabolism
      and biosynthesis of secondary metabolites which is seen to be altered under
      stress conditions like drug resistance. CONCLUSIONS AND CLINICAL RELEVANCE: The
      information provided about the metabolic pathways modulated when contrasting
      these two phenotypes may lead to the development of new strategies to block
      parasite differentiation within the host and to also circumvent the problem of
      drug resistance. This proteomic study also offers new grounds for the
      investigation of novel hypothetical proteins potentially playing a role in
      evolutionary biology the knowledge of which is essential for treatment of
      patients co-infected with these two kinetoplastid parasites.

PMID- 29469989
TI  - Density and location of CD3+ and CD8+ tumor-infiltrating lymphocytes correlate
      with prognosis of oral squamous cell carcinoma.
AB  - BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are regarded as adaptive immune
      response of the host to cancer cells and valuable prognostic factors. Here, we
      sought to characterize the densities and locations of CD3+ and CD8+ TILs in
      primary oral squamous cell carcinoma (OSCC) samples and assess their
      clinicopathological and prognostic significance. METHODS: A total number of 169
      OSCC samples from 2 independent patient cohorts (Nanjing cohort, 93 cases; Wuxi
      cohort, 76 cases) were retrospectively collected. The numbers of CD3+ and CD8+
      TILs at tumor center (CT) and invasive margin (IM) of OSCC were identified by
      immunohistochemistry and calculated. The optimal cutoff values for CD3+ and CD8+
      TILs to stratify patients were determined by X-tile software in Nanjing cohort
      and further utilized in Wuxi cohort. The associations between CD3+ /CD8+ TILs and
      clinicopathological parameters or patient survival were assessed. The prognostic
      values of CD3+ / CD8+ TILs were evaluated by Cox regression analyses. RESULTS:
      CD3+ and CD8+ TILs were identified at both CT and IM and enriched at IM. High
      density of CD3+ TILs at IM (CD3 IM) was significantly associated with increased
      overall and disease-specific survival (P < .05). High density of CD8+ TILs at CT
      (CD8 CT) was significantly associated with increased overall but not disease
      specific survival. Moreover, CD3 IM and CD8 CT were identified as independent
      prognostic factors for patient survival. CONCLUSIONS: Our findings provide
      further evidence to support the prognostic values of CD3+ and CD8+ TILs for OSCC,
      suggesting that TIL subsets might be viable biomarkers and therapeutic targets
      with translational significance.

PMID- 29469991
TI  - Gene Expression on DNA Biochips Patterned with Strand-Displacement Lithography.
AB  - Lithographic patterning of DNA molecules enables spatial organization of cell
      free genetic circuits under well-controlled experimental conditions. Here, we
      present a biocompatible, DNA-based resist termed "Bephore", which is based on
      commercially available components and can be patterned by both photo- and
      electron-beam lithography. The patterning mechanism is based on cleavage of a
      chemically modified DNA hairpin by ultraviolet light or electrons, and a
      subsequent strand-displacement reaction. All steps are performed in aqueous
      solution and do not require chemical development of the resist, which makes the
      lithographic process robust and biocompatible. Bephore is well suited for
      multistep lithographic processes, enabling the immobilization of different types
      of DNA molecules with micrometer precision. As an application, we demonstrate
      compartmentalized, on-chip gene expression from three sequentially immobilized
      DNA templates, leading to three spatially resolved protein-expression gradients.

PMID- 29469992
TI  - Reproductive outcome of patients undergoing in vitro fertilisation treatment and
      diagnosed with bacterial vaginosis or abnormal vaginal microbiota: a systematic
      PRISMA review and meta-analysis.
AB  - BACKGROUND: Despite recent efforts, the risks associated with bacterial vaginosis
      (BV) or abnormal vaginal microbiota in IVF patients are not well-established.
      OBJECTIVES: We aimed to evaluate the risks associated with BV in IVF patients
      using meta-analysis. SEARCH STRATEGY: Following preliminary searches to find
      relevant keywords and MeSH terms, a systematic search was performed in PubMed
      (MEDLINE) in September 2017. SELECTION CRITERIA: The population was infertile
      women attending IVF treatment. The exposure was BV or abnormal vaginal
      microbiota. Outcomes included live birth rate, early spontaneous abortion rate
      and clinical pregnancy rate. DATA COLLECTION AND ANALYSIS: Data were collected
      for each study and for each outcome using a summary of findings table. If
      appropriate, data were quantitatively assessed using meta-analysis, sensitivity
      analysis, funnel plots and GRADE evidence assessment were performed for the above
      mentioned outcomes. MAIN RESULTS: A total of 12 studies were eligible, comprising
      a total of 2980 patients. The prevalence of BV was 16% (95% CI 15-18%) in the
      general study population and tubal factor infertility was highly prevalent in
      patients diagnosed with BV compared with normal vaginal microbiota patients (P =
      0.001). Despite a significant association with early spontaneous abortion
      [relative risk (RR) 1.68, 95% CI 1.24-2.27], BV did not significantly impact the
      live birth rate (RR 1.47, 95% CI 0.96-1.57) or the clinical pregnancy rate (RR
      0.93, 95% CI 0.75-1.15). CONCLUSIONS: BV is associated with tubal factor
      infertility and early spontaneous abortion. However, the quality of evidence was
      very low and the equivocal results justify the need for further research.
      TWEETABLE ABSTRACT: Abnormal vaginal microbiota is associated with early
      spontaneous abortion in IVF patients.

PMID- 29469993
TI  - Asthma among adult patients presenting with dyspnea to the emergency department:
      An observational study.
AB  - INTRODUCTION: Shortness of breath is a common presenting symptom to the emergency
      department (ED) that can arise from a myriad of possible diagnoses. Asthma is one
      of the major causes. OBJECTIVE: The aim of this study was to describe the
      demographic features, clinical characteristics, management and outcomes of adults
      with an ED diagnosis of asthma who presented to an ED in the Asia Pacific region
      with a principal symptom of dyspnea. METHODS: Planned sub-study of patients with
      an ED diagnosis of asthma identified in the Asia, Australia and New Zealand
      Dyspnoea in Emergency Departments (AANZDEM) study. AANZDEM was a prospective
      cohort study conducted in 46 EDs in Australia, New Zealand, Singapore, Hong Kong
      and Malaysia over three 72 hour periods in May, August and October 2014. Primary
      outcomes were patient epidemiology, clinical features, treatment and outcomes
      (hospital length of stay (LOS) and mortality). RESULTS: Of the 3044 patients with
      dyspnea, 387 (12.7%) patients had an ED diagnosis of asthma. The median age was
      45 years, 60.1% were female, 16.1% were active or recent smokers and 30.4%
      arrived by ambulance. Inhaled bronchodilator therapy was initiated in 88.1% of
      patients, and 66.9% received both inhaled bronchodilators and systemic
      corticosteroids. After treatment in the ED, 65.4% were discharged. No death was
      reported. CONCLUSION: Asthma is common among patients presenting with a principal
      symptom of dyspnea in the ED of the Asia Pacific region. There was a suboptimal
      adherence to international guidelines on investigations and treatments of acute
      asthma exacerbations presenting an opportunity to improve the efficiency of care.

PMID- 29469994
TI  - What is your diagnosis? Cutaneous nodules and atypical blood cells in a dog.

PMID- 29469995
TI  - Hypobaric live high-train low does not improve aerobic performance more than live
      low-train low in cross-country skiers.
AB  - Live high-train low (LHTL) using hypobaric hypoxia was previously found to
      improve sea-level endurance performance in well-trained individuals; however,
      confirmatory controlled data in athletes are lacking. Here, we test the
      hypothesis that natural-altitude LHTL improves aerobic performance in cross
      country skiers, in conjunction with expansion of total hemoglobin mass (Hbmass ,
      carbon monoxide rebreathing technique) promoted by accelerated erythropoiesis.
      Following duplicate baseline measurements at sea level over the course of 2
      weeks, nineteen Norwegian cross-country skiers (three women, sixteen men, age 20
      +/- 2 year, maximal oxygen uptake (VO2 max) 69 +/- 5 mL/min/kg) were assigned to
      26 consecutive nights spent at either low (1035 m, control, n = 8) or moderate
      altitude (2207 m, daily exposure 16.7 +/- 0.5 hours, LHTL, n = 11). All athletes
      trained together daily at a common location ranging from 550 to 1500 m (21.2% of
      training time at 550 m, 44.2% at 550-800 m, 16.6% at 800-1100 m, 18.0% at 1100
      1500 m). Three test sessions at sea level were performed over the first 3 weeks
      after intervention. Despite the demonstration of nocturnal hypoxemia at moderate
      altitude (pulse oximetry), LHTL had no specific effect on serum erythropoietin,
      reticulocytes, Hbmass , VO2 max, or 3000-m running performance. Also, LHTL had no
      specific effect on (a) running economy (VO2 assessed during steady-state
      submaximal exercise), (b) respiratory capacities or efficiency of the skeletal
      muscle (biopsy), and (c) diffusing capacity of the lung. This study, showing
      similar physiological responses and performance improvements in the two groups
      following intervention, suggests that in young cross-country skiers, improvements
      in sea-level aerobic performance associated with LHTL may not be due to moderate
      altitude acclimatization.

PMID- 29469996
TI  - A Survey Exploring the Experiences & Attitudes of Dental Implant Clinicians in
      the Management of Peri-implantitis within the United Kingdom.
AB  - Peri-implantitis remains one of the most challenging complications that could
      threaten the long-term survival of implants. The aim of this survey is to explore
      the experiences, attitudes and challenges that face clinicians in the management
      of peri-implantitis. A validated online questionnaire was emailed to implant
      clinicians in the United Kingdom. 72 clinicians responded to the questionnaire,
      all of whom face many challenges during the treatment of peri-implantitis, with
      79% finding difficulties due to lack of treatment consensus and 78% finding
      treatment outcomes unpredictable. This survey highlights the marked differences
      in opinion and attitudes of clinicians in the management of peri-implantitis.

PMID- 29469997
TI  - The Influence of Nitrile Gloves on the Setting Behavior of Polyvinyl Siloxane
      Putty Impression Materials.
AB  - OBJECTIVE: The purpose of this study was to assess the gelation and
      polymerization time of three polyvinyl siloxane (PVS) putty materials and to
      determine if those times were affected by nitrile gloves under different
      conditions. MATERIALS AND METHODS: Ten specimens (n=10) were obtained for each
      PVS putty material (Express STD, 3M ESPE; Extrude Xtra, Kerr and Exafast, GC) and
      tested under different conditions (gloves washed, gloves unwashed and hands
      contaminated). The gelation and polymerization time were measured using an
      oscillating rheometer and recorded for 400 s at 37 degrees C to simulate the oral
      environment. RESULTS: The mean gelation time of hand contaminated specimens was
      157.50 minutes and was significantly slower than that by using nitrile washed
      gloves (mean=117.94, p=.004) and by using unwashed gloves (mean=99.46, p?0.001).
      Unwashed gloves had significantly quicker gelation times compared to washed
      gloves (p=.046). The gelation time was significantly delayed with Exafast
      compared to Extrude Xtra and Express STD across all the different types of glove
      conditions (p?0.043). No significant differences were observed between
      polymerization time with Exafast and Extrude Xtra Putty. CONCLUSIONS: Extrude
      Xtra putty material had significantly better performance than GC Exafast and
      Express. Hand contaminated specimens were affected by the gelation/polymerization
      time.

PMID- 29469998
TI  - The Effect of Complete Denture Occlusion on Function and Patient Quality of Life:
      Systematic Review.
AB  - Edentulism presents an ongoing challenge for prosthodontic dentistry. Many
      aspects of complete denture construction lack contemporary evidence. One such
      aspect is denture occlusion. Balanced occlusion (BO) has become the prevailing
      occlusal scheme. It has been suggested that canine guidance (CG) is unsuitable
      for complete denture occlusion due to an increased risk for tipping of the
      prostheses. However it may be indicated in patients with minimal alveolus
      resorption. There has been limited evidence suggesting the superiority of either
      occlusal scheme over another. This article investigates the available literature
      assessing complete denture occlusion by means of clinical trials or reviews of
      evidence. We utilised PRISMA guidelines to investigate the effect of complete
      denture occlusal scheme (balance occlusion vs. canine guidance) on functional or
      quality of life. Seven studies were included for review. All studies were poor to
      moderate quality with the majority lacking randomisation, blinding and
      demographic data from the study sample. The available evidence suggests that the
      differences between occlusal schemes may be small, challenging the notion that BO
      may be the optimal occlusal scheme. There is a need for high-quality clinical
      research, investigating both chewing ability and quality of life in complete
      denture wearers in the long-term.

PMID- 29469999
TI  - A Systematic Review and Meta-Analysis of Baseline Ohip-Edent Scores.
AB  - BACKGROUND: OHIP-EDENT is widely used in the literature to assess Oral-Health
      Related-Quality-of-Life (OHRQoL) for edentulous patients. However the normal
      variance and mean of the baseline OHIP scores has not been reported. It would
      facilitate critical appraisal of studies if we had knowledge of the normal
      variation and mean of baseline OHIP-EDENT scores. An established figure for
      baseline OHIP-EDENT, obtained from a meta-analysis, would simplify comparisons of
      studies and quantify variations in initial OHRQoL of the trial participants.
      OBJECTIVES: The aim of this study is to quantify a normal baseline value for pre
      operative OHIP-EDENT scores by a systematic review and meta-analysis of the
      available literature. METHODS: A systematic literature review was carried. 83
      papers were identified that included OHIP-EDENT values. After screening and
      eligibility assessment, 7 papers were selected and included in the meta-analysis.
      RESULTS: A meta-analysis for the 7 papers by a random-effect model yielded a mean
      baseline OHIP-EDENT score of 28.63 with a 95% Confidence intervals from 21.93 to
      35.34. CONCLUSION: A pre-operative baseline OHIP-EDENT has been established by
      meta-analysis of published papers. This will facilitate the comparison of the
      initial OHRQoL of one study population to that found elsewhere in the published
      literature.

PMID- 29470000
TI  - Burnout or Joy?

PMID- 29470001
TI  - No Fear: Be Proactive to End Workplace Violence and Bullying.

PMID- 29470002
TI  - Complementary Therapies for Pain Among Individuals Receiving Hemodialysis: A
      Systematic Review.
AB  - Pain is a major problem for individuals undergoing hemodialysis and can lead to
      decreased quality of life when ineffectively managed. Pain is often reported as
      burdensome; thus, nurses must learn effective, nonpharmacological adjuncts to
      help care for symptomatic patients. The purpose of this review was to identify
      non-pharmacologic complementary therapies and evaluate their effectiveness in
      minimizing pain among individuals undergoing hemodialysis. Multiple complementary
      interventions were identified, and several reduced pain, but evidence is
      qualified by limitations in study methods. Complementary therapies have the
      potential to reduce pain among individuals undergoing hemodialysis; however, more
      research is needed.

PMID- 29470003
TI  - Comfort and Fluid Retention in Adult Patients Receiving Hemodialysis.
AB  - Successful hemodialysis treatments for patients with renal failure depend on
      patient adherence to prescribed treatment regimens. Lack of adherence may
      contribute to patient discomfort between hemodialysis treatments. This article
      reports a descriptive, correlational feasibility study that utilized Kolcaba's
      Comfort Theory as a framework. The purpose of the study was to determine a
      potential relationship between comfort and fluid retention (a proxy for
      adherence) in adults with end stage renal disease receiving hemodialysis. A
      convenience sample of 51 patients receiving hemodialysis was studied. Comparisons
      of patient weight gain between hemodialysis treatment sessions measured fluid
      retention by proxy. Results indicated no significant relationship between the
      variables of comfort and adherence to fluid restrictions. However, this finding
      has potential to support clinical practice to minimize weight gain to sustain
      comfort. Awareness of comfort as a consideration for adherence to prescribed
      treatment regimens may help nurses coach individuals to improve treatment
      adherence.

PMID- 29470004
TI  - Accuracy and Utility of Estimating Lean Body Mass and Nutritional Status in
      Patients with Chronic Kidney Disease on Long-Term Hemodialysis Using
      Anthropometric Skinfold Thickness Measurements.
AB  - Malnutrition is common in patients on hemodialysis (prevalence of 30% to 50%) and
      is associated with higher mortality. Lean body mass (LBM) assessment is an
      accurate way of assessing nutritional status. The dual-energy X-ray
      absorptiometry (DEXA) scan is a reliable method in assessing body compositions
      and LBM; however, it is expensive and largely inaccessible. Anthropometric
      skinfold thickness measurement (ASFM) is useful in assessing LBM. It is cheaper
      and accessible, but underutilized clinically. The subjective global score (SGA)
      is a well-established method of assessing nutritional status. All three methods
      of assessing nutritional status were compared. In this pilot observational study,
      there was a significant correlation between LBM% estimated by DEXA and ASFM (mean
      difference -1.46% [95% CI -4.09 to 1.18]; LOA -14.0 to 11.1). Nutritional status
      by SGA could only detect those severely malnourished when using LBM% by ASFM as
      comparison. Our study demonstrated that ASFM is a useful method of assessing LBM
      and nutritional status, which can be easily utilized clinically.

PMID- 29470005
TI  - Factors Influencing the Introduction of a Process of Advance Care Planning in
      Outpatient Hemodialysis Facilities.
AB  - Individuals with kidney failure on outpatient hemodialysis therapy may experience
      many biopsycho social complications and existential concerns. Consequently, there
      is a need to implement a process of advance care planning to effectively meet the
      extensive needs of these individuals. However, this article suggests there are
      various barriers in some outpatient hemodialysis facilities that may hinder the
      introduction of advance care planning. This article provides a critical
      discussion of some of these elements, including increased time pressure, nurse
      patient communication, and the nurse-patient relationship. The article also makes
      recommendations that would facilitate the implementation of a process of advance
      care planning in outpatient hemodialysis facilities.

PMID- 29470006
TI  - Oxygen Saturation and Heart Rate Variations as Predictors of Intradialytic
      Hypotension.
AB  - AIntradialytic hypotension (IDH) occurring during hemodialysis (HD) may cause
      severe complications and can be life-threatening. IDH is a common symptom in
      patients with end stage renal disease undergoing HD. Currently, no effective
      predictive models for IDH exist. This study analyzed data on variations in oxygen
      saturation (SaO2) and heart rate (HR) in 68 patients during their HD sessions by
      using sequence alignment and Boolean algebra. Three classifiers derived from SaO2
      and HR variation data were developed as predictors for predetermining IDH
      occurrence within 30 minutes. The accuracy of these classifiers in predicting IDH
      occurrence was approximately 80%. SaO2 and HR variations can potentially be used
      as predictors for developing an alarm system for detecting IDH occurrence.

PMID- 29470007
TI  - Women and Kidney Disease: Reflections on World Kidney Day 2018.
AB  - World Kidney Day and International Women's Day 2018 are commemorated on the same
      day (March 8), an opportunity to highlight the importance of women's health, and
      particularly, their kidney health. On its 13th anniversary, World Kidney Day
      promotes affordable and equitable access to health education, health care, and
      prevention for all women and girls in the world. In this article, we focus on
      what we do and do not know about women, kidney health, and kidney disease, and
      what we might learn in the future to improve outcomes worldwide.

PMID- 29470008
TI  - Quality Assessment and Performance Improvement: Oversight for Patient Safety.

PMID- 29470009
TI  - Interventions for Improving Interdialytic Weight Gains in At-Risk Patients on
      Hemodialysis at NYU-Winthrop Dialysis Center - What Works?

PMID- 29470010
TI  - Nonalcoholic Steatohepatitis.

PMID- 29470011
TI  - Nonalcoholic Steatohepatitis.

PMID- 29470012
TI  - Nonalcoholic Steatohepatitis.

PMID- 29470013
TI  - Nonalcoholic Steatohepatitis.

PMID- 29470014
TI  - The Colour Treatment: A Convergence of Art and Medicine at the Red Cross Russell
      Lea Nerve Home.
AB  - When the Red Cross opened its new convalescent home at Russell Lea in Sydney in
      1919, it contained a coloured room designed for treating 'nerve cases'. This room
      was painted by Roy de Maistre, a young artist, and was modelled on the Kemp
      Prossor colour scheme trialled at the McCaul Convalescent Hospital in London for
      the treatment of shell shock. Dubbed the 'colour cure' by the popular press, this
      unconventional treatment was ignored by the Australian medical profession. The
      story of de Maistre's colour experiment is not widely known outside the
      specialist field of Australian art history. Focusing on the colour room as a
      point of convergence between art and medicine in the context of the First World
      War, this article investigates Red Cross activities and the care of soldiers
      suffering from nervous conditions.

PMID- 29470015
TI  - Introduction. Towards a Contemporary Historiography of Amateurs in Science (18th
      20th Century).
AB  - The last few decades have seen considerable growth in the role played by amateurs
      in the sciences. With the development of new techniques for collecting
      information, new virtual networks and the emergence of new problematics calling
      for the participation of citizens, this role has also become more visible, while
      the modern boundary between professionalism and amateurism, first erected in the
      19th century, has been shaken. These contemporary developments have changed our
      perspective on amateurs in science and brought forth questions and analyses that
      sometimes coincide with recent inflections in the history of science.Thus it is
      now possible to take a new approach to the historical study of amateurs in
      contemporary science. This introduction hopes to demonstrate this, while the
      essays brought together in this volume, some of which explore extreme cases,
      reveal the very relative nature of the definition of the "amateur" category and
      how complex and fertile its implementation has been in the history of science.

PMID- 29470016
TI  - [Neither Pedants nor Amateurs? Psychological Journals in Germany in the last
      three Decades of the 18th Century].
AB  - Neither pedants nor amateurs? Psychological journals in Germany in the last three
      decades of the 18th century The Magazin zur Erfahrungsseelenkunde introduced a
      new tone in the evolving field of psychology. For the first time, attention was
      paid not to the abstract relationships between body and soul, but to suffering
      individuals from the "common folk". The collection and systematic publication
      ofaccounts of readers should eventually allow the formulation of an empirical
      "science of the soul". The readers would eventually send accounts of personal and
      experienced "cases". By 1800, this conception of the science of psychology was
      called into question by educated philosophers who, in journals opened only to
      specialists, endeavored to develop a more professional psychology. They
      nevertheless failed in formulating general criteria of scientificity. The main
      argument of this article is that the distinction between amateurs and scientists
      was not an outcome of the inner evolution of the field of psychology, but that it
      developed through practices of communication in which periodicals play a major
      role.

PMID- 29470017
TI  - [Scholars and Amateurs in Ornithology around 1800: Sharing Literature].
AB  - Ornithology has emerged as a science at the turn of the 18th century. To become a
      self-sufficient scientific discipline, studies of birds had to distinguish
      themselves from luxury, trade and poetry. Scholars had to invent new ways of
      writing, different from the beautiful and ornamented books on birds, even if
      these books were often published by other scholars who had been expelled from
      academic institutions and therefore considered as "amateurs". The same scholars
      needed the help of "amateurs" in order to observe and explain bird migration.
      First ornithological discourses in Europe and the United States illustrate the
      relationships between scholars, authors and "amateurs" and show how these words
      can be used in different meanings.

PMID- 29470018
TI  - [The "Chacornac Affair": the Rise and Stigmatizatin of a State Astronomer].
AB  - This article traces the unusual astronomical career of Jean Chacornac (1823-1873)
      during the French Second Empire. This clerk in a bazaar in Marseille became in
      just a few years astronomer at the Paris imperial observatory, and was then
      brutally expelled from this prestigious institution. The "Chacornac affair",
      largely forgotten, was an asymmetric struggle between a self-taught astronomer
      and the most famous professional French astronomer of the time, Urbain Le
      Verrier. Through the study of this case, we want to shed a light on people and
      practices kept on the margins of science by the process of professionalization of
      astronomy. Although he was excluded from the institution, Chacornac tried to
      continue to be an astronomer, independently, "from below". But the construction
      of a new social identity for State astronomy, in particular by Le Verrier, was
      inseparable from the attribution of indelible social stigma, which made Chacornac
      an "obligatory amateur".

PMID- 29470019
TI  - [Entomology around 1900: an Amateur Science?].
AB  - At the turn of the twentieth century, French entomology seemed divided between a
      multitude of fans and few official scholars. On the one hand, thenetwork of the
      French Entomological Society, and on the other, a chair at the Museum national
      d'histoire naturelle. To illustrate this duality betweenacademic entomology and a
      more domestic entomology, we present a study based on two men: Charles Janet, a
      little-known province engineer who could be seen as a mere amateur among the
      professionals, Eugene-Louis Bouvier who was a scholar at the Museum national
      d'histoire naturelle and the Academy of Sciences. The biographical approach
      developed here will allow us to meet close associates of these two men.
      Considering their own perceptions we will see how these actors situated
      themselves within their discipline. This approach will allow us to give a broader
      picture of French entomologists around 1900: their number, their institutions,
      their relationships and their means of communication. This text shows that the
      amateur/professional dichotomy is an unsuitable tool to describe entomology at
      that time.

PMID- 29470020
TI  - [Marcel Sembat's Psychology: the Hobby of a Politician?
AB  - The socialist politician Marcel Sembat's unpublished manuscripts revealthe
      unexpected figure of a diarist with a passion for his own intimate, bodily,sexual
      and affective economy, and of an autodidact and sometimes polemicalreader of
      psychology (for instance Pierre Janet's). Sembat was recognizednonetheless as a
      potentially publishable author by Georges Dumas, the editorof the Journal de
      psychologie normale et pathologique, who asked him tocontribute an article -
      which was never published - on dreaming. Sembatwas also particularly receptive to
      Freud's early conceptions of sexuality. WasMarcel Sembat an amateur, like the
      painter Ingres playing the violin? Couldhe be characterized as a "psychologist
      from below"? As a dilettante? Orsimply as a cultivated man according to the
      meaning this period ascribedto the term?

PMID- 29470021
TI  - [Amateurism in Geology: the French Reception of the Continental Drift Theory
      (1920-1950)].
AB  - At the beginning of the XXth century, Wegener proposed a theory - that of the
      roaming drift of the continents - unifying the rival theories of the Europeans
      and the Americans. As the work of a non-specialist who didn't trouble himself
      with specific details, it raised numerous criticisms from specialists in various
      disciplines though others welcomed and supported it. Some even understood that
      despite its flaws, it started a new research program. Paradoxically, as regards
      its simplicity, nonspecialists - engineers, popularizers, secondary school
      teachers and even believers in para-sciences - gave it a favorable reception.
      Being amateurs, they continued to endorse it when specialists abandoned it.

PMID- 29470022
TI  - [Anne Berman (1889-1979): a "Mere Secretary" in the French Psychoanalytic
      Movement?].
AB  - This article is focused on the figure of personal secretary in the history of
      science with the example of Anne Berman (1889-1979) who was, between1933 and
      1962, the secretary for the psychoanalyst Marie Bonaparte (1882-1962). Berman was
      not a psychoanalyst and psychoanalytic historiography considers her as a minor
      figure. However, her career as a personal secretary and her role in the French
      psychoanalytic movement should be considered in conjunction with her involvement
      with the feminist movement. This pharmacist by training has indeed played a
      prominent role within the Soroptimist, which was a movement that championed the
      professional interest of women and prides female excellence. In the case of
      Berman, the status of personal secretary did not enable her to gain lasting
      recognition by psychoanalysts, but only a weak and fragile legitimacy.

PMID- 29470024
TI  - 'We Were More Radical back then': Victoria's First Self-Advocacy Organisation for
      People with Intellectual Disability.
AB  - This article is concerned with exploring the historical development of Reinforce,
      the oldest self-advocacy organisation for people with intellectual disability in
      Victoria. In particular, it considers how governmental indifference, as well as
      ad hoc funding and support, has hindered the growth of the organisation and, more
      generally, the growth of the self-advocacy movement in Victoria. By obtaining a
      deeper understanding of the input from the policy makers, professionals, and
      supporters working in the field of intellectual disability, we can begin to
      comprehend some of the reasons for the comparatively slow development of self
      advocacy in this country.

PMID- 29470023
TI  - The Red Cross and the Liverpool Field Hospital, Hope and Despair during 1915.
AB  - The outbreak of the First World War in August 1914 was met with much jingoistic
      enthusiasm by the Australian population. Men volunteered in their hundreds for
      service for God, King, and Country; to defend the Empire; for adventure; and to
      see the world. Women on the homefront formed up Red Cross branches across the
      country in small country towns and city suburbs to serve 'their boys'.
      Unfortunately for the men who enlisted their desire to serve the Empire was not
      met with a similar level of organisational efficiency by authorities in
      Australia. The military were completely overwhelmed by the progress of the war,
      especially the level of casualties that resulted from the Gallipoli campaign.

PMID- 29470025
TI  - Travelers, Patent Medicines, and Pharmacopeias: American Pharmacy and British
      India, 1857 to 1931.

PMID- 29470026
TI  - From Pharmacien to First Pharmacist.

PMID- 29470027
TI  - Whitelaw Ainslie: Pioneer in Promoting Indigenous Indian Drugs.

PMID- 29470028
TI  - Recovering and Expanding Mozella Esther Lewis's Pioneering History of African
      American Pharmacy Students, 1870-1925.

PMID- 29470029
TI  - History of the Negro in Pharmacy.

PMID- 29470030
TI  - Development and Use of a Video about the History of Pharmacy: The Case of Quebec.

PMID- 29470033
TI  - Edward Kremers (1865-1941) Reformer of American Pharmaceutical Education.

PMID- 29470034
TI  - Imperial Medicine in a Changing World: The Fourth International Congresses on
      Tropical Medicine and Malaria, 1948.
AB  - The close connections between colonialism and tropical medicine have been widely
      discussed by historians over the last fifty years. However, few authors consider
      the relationship between tropical medicine and European and North American
      imperialism in the immediate post-World War II period. This article examines the
      Fourth International Congresses on Tropical Medicine and Malaria, held jointly in
      Washington in 1948. Using the research presented during the conference, it
      questions to what degree the specialisation had changed in the postwar period. It
      argues that although some changes are discernable, imperial traditions and
      relationships remained firmly embedded within the tropical medicine of the
      congress.

PMID- 29470035
TI  - Turning Points in Political and Health Policy History: The Case of Cambodia 1975
      2014.
AB  - Since 1975, Cambodia has transitioned through three distinct political periods of
      totalitarian, centralist, and neo liberal rule. In order to understand the
      challenges these political reforms present for health systems and policies, this
      case study charts events in health policy and political history in Cambodia
      between 1975 and 2014. Findings illustrate the interconnections of health and
      history, the balancing of tradition and modernity in health management and
      medical practice, and the shift in policy positions in response to political and
      economic reform. This historical view has the potential to enhance the capability
      of policy makers to not only understand the origins of current health policy
      positions, but also to anticipate and respond more flexibly to emerging health
      policy challenges.

PMID- 29470036
TI  - The Hangover: The Early and Lasting Effects of the Controversial Incorporation of
      X-Ray Technology into Chiropractic.
AB  - Chiropractic first adopted the X-ray in 1910 for the purpose of demonstrating
      tiny misalignments of spinal bones, theorised to cause all disease, which they
      called chiropractic subluxations. This paper explores the apparent contradiction
      and resultant controversy of a system of natural healing adopting a medical
      technology. It centres on the actions of B.J. Palmer, the first chiropractor to
      use X-rays. It also clarifies details of Palmer's decision to incorporate the
      technology and interprets the change in the sociological context of boundary
      work. The continuing use of the subluxation paradigm for radiography by
      chiropractors has had a lingering effect on the profession, a metaphorical
      hangover of vitalism that is not consistent with modern healthcare practice. As a
      result of this conflict, arguments within the profession on the use of X-rays
      contribute to the continuing schism between evidence-based and subluxation-based
      chiropractors.

PMID- 29470037
TI  - 'The Right Time and the Right Place': An Interview with Jacques Miller.
AB  - Professor Jacques F.P. Miller spoke about his career in immunology with Warwick
      Anderson on 3 February 2014. Born in Nice, France, Miller attended high school
      and medical school in Sydney, Australia. As a Ph.D. student and postgraduate
      researcher in London, Miller discovered the immunological function of the thymus
      gland. Spending the rest of his career at the Walter and Eliza Hall Institute for
      Medical Research in Melbourne, Miller conducted pioneering research in lymphocyte
      population dynamics and the mechanisms of the human immune response. With Graham
      Mitchell, he demonstrated that mammalian lymphocytes can be divided into what
      became known as T cells and B cells, which interact to produce antibodies.

PMID- 29470038
TI  - Introduction: Australian Perspectives: Genocide, the Health Professions, and an
      Inglorius Past.

PMID- 29470039
TI  - Unfathomable Journey: The Context of Dr. Otto Walter's Departure from Australia.
AB  - Fifty years ago, erstwhile eminent Jewish physician Dr Otto Walter abandoned life
      in Australia to return to Austria, leaving his crestfallen young grandson, Garry,
      to wonder why he had gone. In this paper, the author explores the possible
      reasons for his grandfather's departure, weaving in aspects of Otto's
      extraordinary life, including the flight from Vienna after Kristallnacht (the
      German Reich's coordinated night of attacks on Jewish property), and the
      struggles to stay one step ahead of the Nazis in Europe. Otto was to settle in
      the British Mandate for Palestine (later Israel), before coming to Australia in
      1949 on the Cyrenia-serving as ship's doctor for Jewish refugees. In Australia,
      the consummate medical skills that had proven life-saving for Otto's family, were
      not formally recognised, marking the end of a distinguished career.

PMID- 29470040
TI  - Courage under Adversity: Luba Bielicka-Blum (1906-1973) and the Nursing School of
      the Warsaw Ghetto.
AB  - The Warsaw Ghetto was a place where Jews were kept until deportation to Nazi
      death camps. It contained a nursing school, run by Luba Bielicka-Blum. We explore
      the contribution of Luba Bielicka-Blum to nursing and specifically, the nursing
      school of the Warsaw Ghetto by using primary sources of Bielicka-Blum's
      daughter's archive held by Yad Veshem, supported by secondary sources. We
      conclude that, despite extreme hardship and abject horror, the nursing school in
      the Warsaw Ghetto continued to provide the highest level of nursing education
      possible. The relatively unknown story of Luba Bielicka-Blum and her
      determination to continue the education of nurses in the Warsaw Ghetto
      demonstrates the courage of a nursing leader during dreadful times.

PMID- 29470041
TI  - Doctors and the Armenian and Bosnian Genocides.
AB  - The extensive degree of mass murder that occurred throughout the twentieth
      century saw the rate of non-combatant (civilian) deaths rise by over seventy-five
      percent in the space of seventy years, amounting to a death toll exceeding 170
      million. Where genocides are concerned, the central role of doctors is
      undeniable. Their participation arose from the preoccupation with eugenics for
      improving the health of the nation. From here, their belief in nationalism
      overrode the sacred duty to save lives. These doctors descended into moral
      anarchy, breaching an ethical code of two millennia. This paper examines the role
      of doctors in the Armenian genocide and that of psychiatrists (notably Radovan
      Karadzic), in the Bosnian genocide. That medicine contains the seeds of its own
      destruction is confirmed by the recurrent involvement of doctors in genocide.

PMID- 29470042
TI  - Fabrication of Charge-Conversion Nanoparticles for Cancer Imaging by Flash
      Nanoprecipitation.
AB  - Traditional charge-conversion nanoparticles (NPs) need the breakage of acid
      labile groups on the surface, which impedes the rapid response to the acidic
      microenvironment. Here, we developed novel rodlike charge-conversion NPs with
      amphiphilic dextran- b-poly(lactic- co-glycolic acid), poly(2-(dimethylamino)
      ethylmethylacrylate)- b-poly(epsilon-caprolactone), and an aggregation-induced
      emission-active probe through flash nanoprecipitation (FNP). These NPs exhibit
      reversible negative-to-positive charge transition at a slightly acidic pH relying
      on the rapid protonation/deprotonation of polymers. The size and the critical
      charge-conversion pH can be further tuned by varying the flow rate and polymer
      ratio. Consequently, the charge conversion endows NPs with resistance to protein
      adsorption at physiological pH and enhanced internalization to cancer cells under
      acidic conditions. Ex vivo imaging on harvest organs shows that charge-conversion
      NPs were predominantly distributed in tumors after intravenous administration to
      mice due to the robust response of NPs to the acidic microenvironment in tumor
      tissue, whereas control NPs or free probes were broadly accumulated in tumor,
      liver, kidney, and lung. These results suggest the great potential of the current
      FNP strategy in the facile and generic fabrication of charge-conversion NPs for
      tumor-targeting delivery of drugs or fluorescent probes.

PMID- 29470043
TI  - A Novel Graphdiyne-Based Catalyst for Effective Hydrogenation Reaction.
AB  - The platinum nanoparticles (Pt NPs) hybrided with nanostructured carbon materials
      with high stability are important for catalyzing hydrogenation reaction. Here we
      reported the fabrication of ultrastable Pt NPs anchored on graphdiyne, in which
      the strong interactions induced by the porous graphdiyne can prevent the thermal
      migration of Pt nanoparticles on the graphdiyne surface, exploiting the strong
      charge transfer interactions from Pt NPs to GDY substrate to tune the electron
      density of Pt NPs. Pt NPs catalyst with size of 2-3 nm showed high performance on
      hydrogenation of aldehydes and ketones to the corresponding alcohols compared
      with commercial Pt-C. Our results indicated that graphdiyne is a promising
      substrate for constructing metal nanoparticle-based heterogeneous catalysts,
      especially for those requiring strong interactions between metal nanoparticles
      and reactants.

PMID- 29470044
TI  - Polycrystalline Diamond Coating of Additively Manufactured Titanium for
      Biomedical Applications.
AB  - Additive manufacturing using selective laser melted titanium (SLM-Ti) is used to
      create bespoke items across many diverse fields such as medicine, defense, and
      aerospace. Despite great progress in orthopedic implant applications, such as for
      "just in time" implants, significant challenges remain with regards to material
      osseointegration and the susceptibility to bacterial colonization on the implant.
      Here, we show that polycrystalline diamond coatings on these titanium samples can
      enhance biological scaffold interaction improving medical implant applicability.
      The highly conformable coating exhibited excellent bonding to the substrate.
      Relative to uncoated SLM-Ti, the diamond coated samples showed enhanced mammalian
      cell growth, enriched apatite deposition, and reduced microbial S. aureus
      activity. These results open new opportunities for novel coatings on SLM-Ti
      devices in general and especially show promise for improved biomedical implants.

PMID- 29470045
TI  - Surface-Enhanced Raman Scattering Detection of Pesticide Residues Using
      Transparent Adhesive Tapes and Coated Silver Nanorods.
AB  - The efficient extraction of analytes from complex and severe environments is
      significant for promoting the surface-enhanced Raman scattering (SERS) technique
      to actual applications. In this paper, a proof-of-concept strategy is proposed
      for the rapid detection of pesticide residues by utilizing the flexible,
      transparent, and adhesive properties of commercial tapes and SERS performance of
      Al2O3-coated silver nanorod (AgNR@Al2O3) arrays. The function of tapes is to
      rapidly transfer the analytes from the actual surface to the SERS substrate. The
      novel "tape-wrapped SERS (T-SERS)" approach was constructed by a simple "paste,
      peel off, and paste again" procedure. The easily obtained but clearly
      distinguished SERS signals allow us to quickly determine the constituents of
      complex surfaces, such as tetramethylthiuram disulfide and thiabendazole
      pesticides from fruits and vegetables, which may be practically applied to food
      safety, environmental monitoring, and industrial production process controlling.

PMID- 29470046
TI  - Unravelling the Structure and Electrochemical Performance of Li-Cr-Mn-O Cathodes:
      From Spinel to Layered.
AB  - To explore a new series of cathode materials with high electrochemical
      performance, the spinel-layered (1 - x)[LiCrMnO4]. x[Li2MnO3.LiCrO2] ( x = 0,
      0.25, 0.5, 0.75, and 1) composites are synthesized with the sol-gel method. X-ray
      diffraction, high-resolution transmission electron microscopy, selected area
      electron diffraction, and Raman spectra reveal that the structure of the (1 -
      x)[LiCrMnO4]. x[Li2MnO3.LiCrO2] cathode materials evolves from spinel to hybrid
      spinel-layered and layered structures with the increase of the Li concentration.
      Test results reveal that the structure and electrochemical performance of (1 -
      x)[LiCrMnO4]. x[Li2MnO3.LiCrO2] ( x = 0.25, 0.5 and 0.75) composites have the
      characteristics of both spinel ( x = 0) and Li-rich layered phases ( x = 1). In
      particular, x = 0.5 and 0.75 electrodes exhibit relatively high capacity
      retention and rate capability, which is mainly ascribed to the synergistic effect
      of the spinel and Li-rich layered phases, the 3D Li-ion diffusion channels of the
      spinel phase, and the low charge-transfer resistance ( Rct) and Warburg diffusion
      impedance ( Wo).

PMID- 29470047
TI  - Heterostructured Nanorings of Fe-Fe3O4@C Hybrid with Enhanced Microwave
      Absorption Performance.
AB  - Microwave absorption is a critical challenge with progression in electronics,
      where fine structural designing of absorbent materials plays an effective role in
      optimizing their microwave absorption properties. Here, we have developed Fe3O4@C
      (FC) and Fe-Fe3O4@C (FFC) hybrid nanorings via a hydrothermal method coupled with
      a chemical catalytic vapor deposition technique. FC and FFC hybrid nanorings have
      fine carbon coating while their size can easily be tunable in a certain range
      from 80-130 to 90-140 nm. The optimized FC and FFC hybrid nanorings bear minimum
      reflection loss (RL) values of -39.1 dB at 15.9 GHz and -32.9 dB at 17.1 GHz,
      respectively, whereas FFC shows an effective absorption bandwidth (RL values < 
      10 dB) ranged from 5.2 to 18 GHz. Such an enhanced microwave absorption
      performance of hybrid nanorings is mainly due to the suitable impedance
      characteristics, multilevel interfaces, and polarization features in nanorings.
      This work provides an approach to design hybrid materials having a complex
      structure to enhance the microwave absorption properties.

PMID- 29470048
TI  - Designing Porphyrinic Covalent Organic Frameworks for the Photodynamic
      Inactivation of Bacteria.
AB  - Microbial colonization of biomedical devices is a recognized complication
      contributing to healthcare-associated infections. One of the possible approaches
      to prevent surfaces from the biofilm formation is antimicrobial photodynamic
      inactivation based on the cytotoxic effect of singlet oxygen, O2(1Deltag), a
      short-lived, highly oxidative species, produced by energy transfer between
      excited photosensitizers and molecular oxygen. We synthesized porphyrin-based
      covalent organic frameworks (COFs) by Schiff-base chemistry. These novel COFs
      have a three-dimensional, diamond-like structure. The detailed analysis of their
      photophysical and photochemical properties shows that the COFs effectively
      produce O2(1Deltag) under visible light irradiation, and especially three
      dimensional structures have strong antibacterial effects toward Pseudomonas
      aeruginosa and Enterococcus faecalis biofilms. The COFs exhibit high
      photostability and broad spectral efficiency. Hence, the porphyrinic COFs are
      suitable candidates for the design of antibacterial coating for indoor
      applications.

PMID- 29470050
TI  - Who Are Your Coauthors? Make Sure To Follow Appropriate Practices.

PMID- 29470049
TI  - A Versatile Route toward the Electromagnetic Functionalization of Metal-Organic
      Framework-Derived Three-Dimensional Nanoporous Carbon Composites.
AB  - Designable electromagnetic parameters accompanied by a low density of metal
      organic framework (MOF)-derived metal/carbon composites are essential
      prerequisites for excellent microwave-absorbing materials. However, the
      conventional route is confined to slight modification of the physicochemical
      properties of metal species and carbon, which also restricts the
      functionalization of MOF-derived materials. Here, a facile technique has been
      improved by making full use of highly porous structure to uniformly introduce
      metallic Co nanoparticles into carbon matrix derived from Cu3(btc)2. Through
      changing the starting amount of Co sources, the composition of the final products
      can be tuned, offering an effective route to control electromagnetic properties.
      Multiple attenuation mechanisms are employed to realize excellent reflection loss
      performance, which can be clarified by modified equivalent circuit mode.
      Effective frequency bandwidth ( fe) over the whole X band can be obtained by
      optimizing interfacial polarization through changing interface area and
      electrical conductivity. Broad fe covering almost the whole Ku band from 12.3 to
      18 GHz with a thin thickness of 1.85 mm can be gained through improving impedance
      matching and enhancing conduction loss. The present work not only sheds light on
      the easy fabrication of high-performance lightweight microwave-absorbing
      materials but also paves the way for extending functionalities of MOF-derived
      carbon composites.

PMID- 29470051
TI  - Porous Zr6L3 Metallocage with Synergetic Binding Centers for CO2.
AB  - Coordination-driven assembly has been widely successful in the synthesis of
      metallocages and used for many applications, such as catalysis. However, studies
      on CO2 adsorption with metallocages have been rarely conducted, compared to other
      well-known cage-type materials, such as porous organic cages. In this study, a
      rational choice of ligand and metal led to the synthesis of a Zr6L3-type
      metallocage, exhibiting exceptional CO2 adsorption properties. CO2 adsorption
      experiments revealed that the metallocage shows highly selective adsorption of
      CO2 over N2 with high CO2 binding energy. Density functional theory calculations
      uncovered the origin of this exceptional affinity for CO2 over N2.

PMID- 29470052
TI  - Flexible Asymmetric Supercapacitor Based on Functionalized Reduced Graphene Oxide
      Aerogels with Wide Working Potential Window.
AB  - Flexible energy storage devices are in great demand since the advent of flexible
      electronics. Until now, flexible supercapacitors based on graphene analogues
      usually have had low operating potential windows. To this end, two dissimilar
      electrode materials with complementary potential ranges are employed to obtain an
      optimum cell voltage of 1.8 V. A low-temperature organic sol-gel method is used
      to prepare two different types of functionalized reduced graphene oxide aerogels
      (rGOA) where Ag nanorod functionalized rGOA acts as a negative electrode while
      polyaniline nanotube functionalized rGOA acts as a positive electrode. Both
      materials comprehensively exploit their unique properties to produce a device
      that has high energy and power densities. An assembled all-solid-state asymmetric
      supercapacitor gives a high energy density of 52.85 W h kg-1 and power density of
      31.5 kW kg-1 with excellent cycling and temperature stability. The device also
      performs extraordinarily well under different bending conditions, suggesting its
      potential to meet the requirements for flexible electronics.

PMID- 29470053
TI  - Ag3PO4@UMOFNs Core-Shell Structure: Two-Dimensional MOFs Promoted Photoinduced
      Charge Separation and Photocatalysis.
AB  - Metal-organic frameworks (MOFs) are a new type of functional material that is
      self-assembled by metal ions and organic ligands. In this paper, a bimetal
      organic framework was synthesized and stripped into two-dimensional nanosheets
      structure via an ultrasonic method. We coated the UMOFNs (ultrathinning MOFs into
      two-dimensional nanosheets) on Ag3PO4 nanoparticles to obtain Ag3PO4@UMOFNs core
      shell photocatalysts. Under visible-light irradiation, the degradation of phenol
      was 100% within 16 min, and the degradation of biphenyl A was 98.9% within 20 min
      via Ag3PO4@UMOFNs (5 wt %). These values were 1.6- and 1.8-times higher than
      Ag3PO4, respectively. The activity of the Ag3PO4@UMOFNs increased due to the
      synergistic effects. The pi-pi bonds of the organic ligands and weak interactions
      between UMOFNs and Ag3PO4 collectively promote charge transfer. In addition,
      matching energy-level structures and a sufficiently large contact area accelerate
      the separation of the photogenerated charges and improve the activity. This
      remarkably improves the photocatalytic activity.

PMID- 29470054
TI  - In Situ Growth of Layered Bimetallic ZnCo Hydroxide Nanosheets for High
      Performance All-Solid-State Pseudocapacitor.
AB  - Two-dimensional (2D) hydroxide nanosheets can exhibit exceptional electrochemical
      performance owing to their shortened ion diffusion distances, abundant active
      sites, and various valence states. Herein, we report ZnCo1.5(OH)4.5Cl0.5.0.45H2O
      nanosheets (thickness ~30 nm) which crystallize in a layered structure and
      exhibit a high specific capacitance of 3946.5 F g-1 at 3 A g-1 for an
      electrochemical pseudocapacitor. ZnCo1.5(OH)4.5Cl0.5.0.45H2O was synthesized by a
      homogeneous precipitation method and spontaneously crystallized into 2D
      nanosheets in well-defined hexagonal morphology with crystal structure revealed
      by synchrotron X-ray powder diffraction data analysis. In situ growth of
      ZnCo1.5(OH)4.5Cl0.5.0.45H2O nanosheet arrays on conductive Ni foam substrate was
      successfully realized. Asymmetric supercapacitors based on
      ZnCo1.5(OH)4.5Cl0.5.0.45H2O nanosheets @Ni foam// PVA, KOH//reduced graphene
      oxide exhibits a high energy density of 114.8 Wh kg-1 at an average power density
      of 643.8 W kg-1, which surpasses most of the reported all-solid-state
      supercapacitors based on carbonaceous materials, transition metal
      oxides/hydroxides, and MXenes. Furthermore, a supercapacitor constructed from
      ZnCo1.5(OH)4.5Cl0.5.0.45H2O nanosheets@PET substrate shows excellent flexibility
      and mechanical stability. This study provides layered bimetallic hydroxide
      nanosheets as promising electroactive materials for flexible, solid-state energy
      storage devices, presenting the best reported performance to date.

PMID- 29470056
TI  - Dynamics and Removal Pathway of Edge Dislocations in Imperfectly Attached PbTe
      Nanocrystal Pairs: Toward Design Rules for Oriented Attachment.
AB  - Using in situ high-resolution TEM, we study the structure and dynamics of well
      defined edge dislocations in imperfectly attached PbTe nanocrystals. We identify
      that attachment of PbTe nanocrystals on both {100} and {110} facets gives rise to
      b = a/2?110? edge dislocations. Based on the Burgers vector of individual
      dislocations, we can identify the glide plane of the dislocations. We observe
      that defects in particles attached on {100} facets have glide planes that quickly
      intersect the surface, and HRTEM movies show that the defects follow the glide
      plane to the surface. For {110} attached particles, the glide plane is collinear
      with the attachment direction, which does not provide an easy path for the
      dislocation to reach the surface. Indeed, HRTEM movies of dislocations for {110}
      attached particles show that defect removal is much slower. Further, we observe
      conversion from pure edge dislocations in imperfectly attached particles to
      dislocations with mixed edge and screw character, which has important
      implications for crystal growth. Finally, we observe that dislocations initially
      closer to the surface have a higher speed of removal, consistent with the strong
      dislocation free surface attractive force. Our results provide important design
      rules for defect-free attachment of preformed nanocrystals into epitaxial
      assemblies.

PMID- 29470057
TI  - Mass Spectrometry-Based Immunoassay for the Quantification of Banned Ruminant
      Processed Animal Proteins in Vegetal Feeds.
AB  - The ban of processed animal proteins (PAPs) in feed for farmed animals introduced
      in 2001 was one of the main EU measures to control the bovine spongiform
      encephalopathy (BSE) crisis. Currently, microscopy and polymerase chain reaction
      (PCR) are the official methods for the detection of illegal PAPs in feed.
      However, the progressive release of the feed ban, recently with the legalization
      of nonruminant PAPs for the use in aquaculture, requires the development of
      alternative methods to determine the species origin and the source (legal or
      not). Additionally, discussions about the need for quantitative tests came up,
      particularly if the zero-tolerance-concept is replaced by introducing PAP
      thresholds. To address this issue, we developed and partially validated a
      multiplex mass spectrometry-based immunoassay to quantify ruminant specific
      peptides in vegetal cattle feed. The workflow comprises a new sample preparation
      procedure based on a tryptic digestion of PAPs in suspension, a subsequent
      immunoaffinity enrichment of the released peptides, and a LC-MS/MS-based analysis
      for peptide quantification using isotope labeled standard peptides. For the very
      first time, a mass spectrometry-based method is capable of detecting and
      quantifying illegal PAPs in animal feed over a concentration range of 4 orders of
      magnitude with a detection limit in the range of 0.1% to 1% (w/w).

PMID- 29470058
TI  - Risk Assessments Show Engineered Nanomaterials To Be of Low Environmental
      Concern.

PMID- 29470059
TI  - Low-Pressure Nanofiltration Hollow Fiber Membranes for Effective Fractionation of
      Dyes and Inorganic Salts in Textile Wastewater.
AB  - In this work, novel loose nanofiltration (NF) hollow fiber membranes with
      ultrahigh water permeability and well-defined nanopore and surface charge
      characteristics were developed for effective fractionation of dyes and inorganic
      salts in textile wastewater treatment. The as-spun NF hollow fiber possesses a
      high pure water permeability (PWP) of 80 L.m-2.h-1.bar-1 with a small pore size
      of 1.0 nm in diameter and a MWCO of 1000 Da. The surface modification by means of
      hyperbranched polyethylenimine (PEI) further lowers the pore diameter to 0.85 nm
      and MWCO to 680 Da. The membrane surface also becomes more hydrophilic and
      positively charged after the PEI modification. Because of the synergistic effects
      from size exclusion and charge repulsion, the newly developed NF hollow fibers
      show high permeation fluxes of 7.0-71.2 L.m-2.h-1 and great rejections of 95.5
      99.9% to various dyes at a low operating pressure of 1 bar. At the same time,
      they have ultralow rejections of less than 10% to inorganic salts (i.e., Na2SO4),
      suggesting that more than 90% of the salts would permeate through the fibers. In
      addition, the two hollow fibers exhibit outstanding performance stability, low
      fouling tendency, and great fouling reversibility. Their fluxes can be brought
      back to be more than 80% of the original values by a simple physical backwash.
      The newly developed loose NF hollow fiber membranes may have great potential for
      effective fractionation and treatment of textile wastewater.

PMID- 29470060
TI  - Rationalizing the Regioselectivity of the Diels-Alder Biscycloaddition of
      Fullerenes.
AB  - The physical factors governing the regioselectivity of the double
      functionalization of fullerenes have been explored by means of density functional
      theory calculations. To this end, the second Diels-Alder cycloaddition reactions
      involving 1,3-butadiene and the parent C60 fullerene as well as the ion
      encapsulated system Li+@C60 have been selected. In agreement with previous
      experimental findings on related processes, it is found that the cycloaddition
      reaction, involving either C60 or Li+@C60, occurs selectively at specific [6,6]
      bonds. The combination of the activation strain model of reactivity and the
      energy decomposition analysis methods has been applied to gain a quantitative
      understanding into the markedly different reactivity of the available [6,6]-bonds
      leading to the observed regioselectivity in the transformation.

PMID- 29470061
TI  - Solid-Phase Extraction Coupled to a Paper-Based Technique for Trace Copper
      Detection in Drinking Water.
AB  - Metal contamination of natural and drinking water systems poses hazards to public
      and environmental health. Quantifying metal concentrations in water typically
      requires sample collection in the field followed by expensive laboratory analysis
      that can take days to weeks to obtain results. The objective of this work was to
      develop a low-cost, field-deployable method to quantify trace levels of copper in
      drinking water by coupling solid-phase extraction/preconcentration with a
      microfluidic paper-based analytical device. This method has the advantages of
      being hand-powered (instrument-free) and using a simple "read by eye"
      quantification motif (based on color distance). Tap water samples collected
      across Fort Collins, CO, were tested with this method and validated against ICP
      MS. We demonstrate the ability to quantify the copper content of tap water within
      30% of a reference technique at levels ranging from 20 to 500 000 ppb. The
      application of this technology, which should be sufficient as a rapid screening
      tool, can lead to faster, more cost-effective detection of soluble metals in
      water systems.

PMID- 29470055
TI  - Unique Molecular Regulation of Higher-Order Prefrontal Cortical Circuits:
      Insights into the Neurobiology of Schizophrenia.
AB  - Schizophrenia is associated with core deficits in cognitive abilities and
      impaired functioning of the newly evolved prefrontal association cortex (PFC). In
      particular, neuropathological studies of schizophrenia have found selective
      atrophy of the pyramidal cell microcircuits in deep layer III of the dorsolateral
      PFC (dlPFC) and compensatory weakening of related GABAergic interneurons. Studies
      in monkeys have shown that recurrent excitation in these layer III microcircuits
      generates the precisely patterned, persistent firing needed for working memory
      and abstract thought. Importantly, excitatory synapses on layer III spines are
      uniquely regulated at the molecular level in ways that may render them
      particularly vulnerable to genetic and/or environmental insults. Glutamate
      actions are remarkably dependent on cholinergic stimulation, and there are
      inherent mechanisms to rapidly weaken connectivity, e.g. during stress. In
      particular, feedforward cyclic adenosine monophosphate (cAMP)-calcium signaling
      rapidly weakens network connectivity and neuronal firing by opening nearby
      potassium channels. Many mechanisms that regulate this process are altered in
      schizophrenia and/or associated with genetic insults. Current data suggest that
      there are "dual hits" to layer III dlPFC circuits: initial insults to
      connectivity during the perinatal period due to genetic errors and/or
      inflammatory insults that predispose the cortex to atrophy, followed by a second
      wave of cortical loss during adolescence, e.g. driven by stress, at the descent
      into illness. The unique molecular regulation of layer III circuits may provide a
      nexus where inflammation disinhibits the neuronal response to stress.
      Understanding these mechanisms may help to illuminate dlPFC susceptibility in
      schizophrenia and provide insights for novel therapeutic targets.

PMID- 29470062
TI  - Temperature Effect on Co-Based Catalysts in Oxygen Evolution Reaction.
AB  - Oxygen evolution reaction (OER), as the critical step in splitting water, is a
      thermodynamically "up-hill" process and requires highly efficient catalysts to
      run. Arrhenius' law suggests that the higher temperature, the faster the reaction
      rate, so that a larger OER current density can be achieved at a lower eta.
      Herein, we report an abnormal temperature effect on the performance of Co-based
      catalysts, e.g., Co3O4, Li2CoSiO4, and Fe-doped Co(OH) x, in OER in alkaline
      electrolytes. The OER performance reached a maximum when the temperature
      increased to 65  degrees C, and the OER performance declined when the temperature
      became higher. The mechanism was investigated by using Co3O4 as a model sample,
      and we propose that at an optimal temperature (around 55-65  degrees C) the main
      rate-determining step changes from OH- adsorption dominant to a mixed mode and
      both the adsorption and the cleavage of the OH group can be rate-determining,
      which leads to the fastest kinetics.

PMID- 29470063
TI  - Prediction of 19F NMR Chemical Shifts for Fluorinated Aromatic Compounds.
AB  - Scaling factors are reported for use in predicting 19F NMR chemical shifts for
      fluorinated (hetero)aromatic compounds with relatively low levels of theory. Our
      recommended scaling factors were developed using a curated data set of 52
      compounds, with 100 individual 19F shifts spanning a range of 153 ppm. With a
      maximum deviation of 6.5 ppm between experimental and computed shifts, or 4% of
      the range tested, these scaling factors allow for the assignment of chemical
      shifts to specific fluorines in multifluorinated aromatics. The utility of this
      approach is highlighted by several structural reassignments.

PMID- 29470064
TI  - Correction to Identification of 4-Phenoxyquinoline Based Inhibitors for L1196M
      Mutant of Anaplastic Lymphoma Kinase by Structure-Based Design.

PMID- 29470066
TI  - Disinfection as a Selection Pressure on RNA Virus Evolution.

PMID- 29470067
TI  - Tunable Robust pacs-MOFs: a Platform for Systematic Enhancement of the C2H2
      Uptake and C2H2/C2H4 Separation Performance.
AB  - As a modulatable class of porous crystalline materials, metal-organic frameworks
      (MOFs) have gained intensive research attention in the domain of gas storage and
      separation. In this study, we report on the synthesis and gas adsorption
      properties of two robust MOFs with the general formula [Co3(MU3-OH)(cpt)3Co3(MU3
      OH)(L)3(H2O)9](NO3)4(guests) n [L = 3-amino-1,2,4-triazole (1) and 3,5-diamino
      1,2,4-triazole (2); Hcpt = 4-(4-carboxyphenyl)-1,2,4-triazole], which show the
      same pacs topology. Both MOFs are isostructural to each other and show MIL-88
      type frameworks whose pore spaces are partitioned by different functionlized
      trinuclear 1,2,4-triazolate-based clusters. The similar framework components with
      different amounts of functional groups make them an ideal platform to permit a
      systematic gas sorption/separation study to evaluate the effects of distinctive
      parameters on the C2H2 uptake and separation performance. Because of the presence
      of additional amido groups, the MOF 2 equipped with a datz-based cluster (Hdatz =
      3,5-diamino-1,2,4-triazole) shows a much improved C2H2 uptake capacity and
      separation performance over that of the MOF 1 equipped with atz-based clusters
      (Hatz = 3-amino-1,2,4-triazole), although the surface area of the MOF 1 is almost
      twice than that of the MOF 2. Moreover, the high density of open metal sites,
      abundant free amido groups, and charged framework give the MOF 2 an excellent
      C2H2 separation performance, with ideal adsorbed solution theory selectivity
      values reaching up to 11.5 and 13 for C2H2/C2H4 (1:99) and C2H2/CO2 (50:50) at
      298 K and 1 bar, showing potential for use in natural gas purification.

PMID- 29470065
TI  - Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist
      Toolbox for Real-Time GPCR Photopharmacology.
AB  - Noninvasive methods to modulate G protein-coupled receptors (GPCRs) with temporal
      and spatial precision are in great demand. Photopharmacology uses photons to
      control in situ the biological properties of photoswitchable small-molecule
      ligands, which bodes well for chemical biological precision approaches.
      Integrating the light-switchable configurational properties of an azobenzene into
      the ligand core, we developed a bidirectional antagonist toolbox for an
      archetypical family A GPCR, the histamine H3 receptor (H3R). From 16 newly
      synthesized photoswitchable compounds, VUF14738 (28) and VUF14862 (33) were
      selected as they swiftly and reversibly photoisomerize and show over 10-fold
      increased or decreased H3R binding affinities, respectively, upon illumination at
      360 nm. Both ligands combine long thermal half-lives with fast and high
      photochemical trans-/ cis conversion, allowing their use in real-time
      electrophysiology experiments with oocytes to confirm dynamic photomodulation of
      H3R activation in repeated second-scale cycles. VUF14738 and VUF14862 are robust
      and fatigue-resistant photoswitchable GPCR antagonists suitable for
      spatiotemporal studies of H3R signaling.

PMID- 29470069
TI  - Photochemistry of fac-[Re(CO)3(dcbH2)( trans-stpy)]+: New Insights on the
      Isomerization Mechanism of Coordinated Stilbene-like Ligands.
AB  - In this work, a novel complex fac-[Re(CO)3(dcbH2)( trans-stpy)]+, (dcbH2 = 4,4'
      dicarboxylic acid-2,2'-bipyridine; trans-stpy = trans-4-styrylpyridine) was
      synthesized and characterized toward its spectroscopic, photochemical, and
      photophysical properties. The experimental data provide new insights on the
      mechanism of photochemical trans-to- cis isomerization of the stilbene-like
      ligand coordinated to Re(I) polypyridyl complexes. The new complex exhibits an
      unusual and strong dependence of the isomerization quantum yield (Phit ->c) on
      the irradiation wavelength. Phit ->c was 0.81 +/- 0.08 for irradiation at 365 nm
      and continuously decreased as the irradiation wavelength is shifted to the
      visible. At 405 nm irradiation Phit ->c is almost 2 orders of magnitude lower
      (0.010 +/- 0.005) than that observed at 365 nm excitation. This behavior can be
      explained by the low-lying triplet metal-to-ligand charge-transfer excited state
      (3MLCT) that hinders the triplet photoreaction mechanism under visible light
      absorption. Under UV irradiation, direct population of styrylpyridine-centered
      excited state (1IL) leads to the occurrence of the photoisomerization via a
      singlet mechanism. Further experiments were performed with the complex
      immobilized on the surface of TiO2 and Al2O3 films. The nonoccurrence of
      isomerization at the oxide surfaces even under UV excitation evidences the role
      of energy gap between the 1IL/1MLCT states on the photochemical/photophysical
      processes. The results establish important relationships between the molecular
      structure and the photoelectrochemical behavior, which can further contribute to
      the development of solid-state molecular switches based on Re(I) polypyridyl
      complexes.

PMID- 29470068
TI  - Reduction of Circulating Cancer Cells and Metastases in Breast-Cancer Models by a
      Potent EphA2-Agonistic Peptide-Drug Conjugate.
AB  - EphA2 overexpression has been associated with metastasis in multiple cancer
      types, including melanomas and ovarian, prostate, lung, and breast cancers. We
      have recently proposed the development of peptide-drug conjugates (PDCs) using
      agonistic EphA2-targeting agents, such as the YSA peptide or its optimized
      version, 123B9. Although our studies indicated that YSA- and 123B9-drug
      conjugates can selectively deliver cytotoxic drugs to cancer cells in vivo, the
      relatively low cellular agonistic activities (i.e., the high micromolar
      concentrations required) of the agents toward the EphA2 receptor remained a
      limiting factor to the further development of these PDCs in the clinic. Here, we
      report that a dimeric version of 123B9 can induce receptor activation at
      nanomolar concentrations. Furthermore, we demonstrated that the conjugation of
      dimeric 123B9 with paclitaxel is very effective at targeting circulating tumor
      cells and inhibiting lung metastasis in breast-cancer models. These studies
      represent an important step toward the development of effective EphA2-targeting
      PDCs.

PMID- 29470070
TI  - Stereoelectronic Interactions Exhibited by 1 JC-H One-Bond Coupling Constants and
      Examination of the Possible Existence of the Intramolecular alpha-Effect in Six
      Membered Oxygen-Containing Heterocycles.
AB  - For more than five decades since its original conception, the alpha-effect has
      been advocated with arguments based on kinetic reactivity data. The present study
      was undertaken with the aim of gathering theoretical information on thermodynamic
      bond energy data in systems that could in principle give rise to intramolecular
      alpha-effects. In particular, oxygen-containing six-membered rings oxa-, 1,2
      dioxa-, 1,3-dioxa-, 1,2,4-trioxa-, and 1,2,4,5-tetraoxacyclohexane were optimized
      at the B3LYP/aug-cc-pVTZ level of theory, and the magnitude of all C-H one-bond
      coupling constants was determined. Furthermore, hyperconjugative interactions
      were evaluated with Natural Bond Orbital analysis. Analysis of the collected
      information leads to the conclusion that ether oxygens are apparently better
      donors than peroxide oxygens; that is, the n(O) -> sigma*(C-Hax) two-orbital/two
      electron interaction seems to be stronger than the n(O-O) -> sigma*(C-Hax) two
      orbital/two-electron interaction, and this finding is contrary to expectations in
      terms of the alpha-effect.

PMID- 29470071
TI  - Isomeric Broadening of C60+ Electronic Excitation in Helium Droplets: Experiments
      Meet Theory.
AB  - Helium is considered an almost ideal tagging atom for cold messenger spectroscopy
      experiments. Although helium is bound very weakly to the ionic molecule of
      interest, helium tags can lead to shifts and broadenings that we recorded near
      963.5 nm in the electronic excitation spectrum of C60+ solvated with up to 100
      helium atoms. Dedicated quantum calculations indicate that the inhomogeneous
      broadening is due to different binding energies of helium to the pentagonal and
      hexagonal faces of C60+, their dependence on the electronic state, and the
      numerous isomeric structures that become available for intermediate coverage.
      Similar isomeric effects can be expected for optical spectra of most larger
      molecules surrounded by nonabsorbing weakly bound solvent molecules, a situation
      encountered in many messenger-tagging spectroscopy experiments.

PMID- 29470072
TI  - Molecular Imaging of Cancer Using X-ray Computed Tomography with Protease
      Targeted Iodinated Activity-Based Probes.
AB  - X-ray computed tomography (CT) is a robust, precise, fast, and reliable imaging
      method that enables excellent spatial resolution and quantification of contrast
      agents throughout the body. However, CT is largely inadequate for molecular
      imaging applications due mainly to its low contrast sensitivity that forces the
      use of large concentrations of contrast agents for detection. To overcome this
      limitation, we generated a new class of iodinated nanoscale activity-based probes
      (IN-ABPs) that sufficiently accumulates at the target site by covalently binding
      cysteine cathepsins that are exceptionally highly expressed in cancer. The IN
      ABPs are comprised of a short targeting peptide selective to specific cathepsins,
      an electrophilic moiety that allows activity-dependent covalent binding, and tags
      containing dendrimers with up to 48 iodine atoms. IN-ABPs selectively bind and
      inhibit activity of recombinant and intracellular cathepsin B, L, and S. We
      compared the in vivo kinetics, biodistribution, and tumor accumulation of IN-ABPs
      bearing 18 and 48 iodine atoms each, and their control counterparts lacking the
      targeting moiety. Here we show that although both IN-ABPs bind specifically to
      cathepsins within the tumor and produce detectable CT contrast, the 48-iodine
      bearing IN-ABP was found to be optimal with signals over 2.1-fold higher than its
      nontargeted counterpart. In conclusion, this study shows the synthetic
      feasibility and potential utility of IN-ABPs as potent contrast agents that
      enable molecular imaging of tumors using CT.

PMID- 29470073
TI  - Molecular Hydrogen Yields from the alpha-Self-Radiolysis of Nitric Acid Solutions
      Containing Plutonium or Americium.
AB  - The yield of molecular hydrogen, as a function of nitric acid concentration, from
      the alpha-radiolysis of aerated nitric acid and its mixtures with sulfuric acid
      containing plutonium or americium has been investigated. Comparison of
      experimental measurements with predictions of a Monte Carlo radiation track
      chemistry model shows that, in addition to scavenging of the hydrated electron,
      its precursor, and the hydrogen atom, the quenching of excited state water is
      important in controlling the yield of molecular hydrogen. In addition, increases
      in solution acidity cause a significant change in the track reactions, which can
      be explained as resulting from scavenging of eaq- by Haq+ to form H*. Although
      plutonium has been shown to be an effective scavenger of precursors of molecular
      hydrogen below 0.1 mol dm-3 nitrate, previously reported effects of plutonium on
      G(H2)alpha between 1 and 10 mol dm-3 nitric acid were not reproduced. Modeling
      results suggest that plutonium is unlikely to effectively compete with nitrate
      ions in scavenging the precursors of molecular hydrogen at higher nitric acid
      concentrations, and this was confirmed by comparing molecular hydrogen yields
      from plutonium solutions with those from americium solutions. Finally, comparison
      between radionuclide, ion accelerator experiments, and model predictions leads to
      the conclusion that the high dose rate of accelerator studies does not
      significantly affect the measured molecular hydrogen yield. These reactions
      provide insight into the important processes for liquors common in the
      reprocessing of spent nuclear fuel and the storage of highly radioactive liquid
      waste prior to vitrification.

PMID- 29470074
TI  - Comment on "HYDROPHOBE Challenge: A Joint Experimental and Computational Study on
      the Host-Guest Binding of Hydrocarbons to Cucurbiturils, Allowing Explicit
      Evaluation of Guest Hydration Free-Energy Contributions".

PMID- 29470075
TI  - Combined Experimental-Theoretical Study of the OH + CO -> H + CO2 Reaction
      Dynamics.
AB  - A combined experimental-theoretical study is performed to advance our
      understanding of the dynamics of the prototypical tetra-atom, complex-forming
      reaction OH + CO -> H + CO2, which is also of great practical relevance in
      combustion, Earth's atmosphere, and, potentially, Mars's atmosphere and
      interstellar chemistry. New crossed molecular beam experiments with mass
      spectrometric detection are analyzed together with the results from previous
      experiments and compared with quasi-classical trajectory (QCT) calculations on a
      new, full-dimensional potential energy surface (PES). Comparisons between
      experiment and theory are carried out both in the center-of-mass and laboratory
      frames. Good agreement is found between experiment and theory, both for product
      angular and translational energy distributions, leading to the conclusion that
      the new PES is the most accurate at present in elucidating the dynamics of this
      fundamental reaction. Yet, small deviations between experiment and theory remain
      and are presumably attributable to the QCT treatment of the scattering dynamics.

PMID- 29470076
TI  - Correction to "Factorial Design Based Multivariate Modeling and Optimization of
      Tunable Bioresponsive Arginine Grafted Poly(cystaminebis(acrylamide)
      diaminohexane) Polymeric Matrix Based Nanocarriers".

PMID- 29470077
TI  - Efficient Upper-Excited State Fluorescence in an Organic Hyperbolic Metamaterial.
AB  - Upper-excited state emission is not usually observed from molecules owing to
      competition with much faster nonradiative relaxation pathways; however, it can be
      made more efficient by modifying the photonic density of states to enhance the
      radiative decay rate. Here, we show that embedding the small molecule zinc
      tetraphenylporphyrin (ZnTPP) in a hyperbolic metamaterial enables an ~18-fold
      increase in fluorescence intensity from the second singlet excited state ( S2)
      relative to that from the lowest singlet excited state ( S1). By varying the
      number of periods in the HMM stack, we are able to systematically tune the ZnTPP
      fluorescence spectrum from red (dominated by emission from S1) to blue (dominated
      by emission from S2) with an instrument-limited decay lifetime <10 ps. Our
      results are consistent with a broadband Purcell enhancement in the radiative rate
      of both transitions predicted via transfer matrix modeling and point to a general
      opportunity to harness upper-excited states for spectrally tunable, ultrafast
      fluorescence via radiative decay engineering.

PMID- 29470078
TI  - Engineering DNA Molecule Bridge between Metal Electrodes for High-Performance
      Molecular Transistor: An Environmental Dependent Approach.
AB  - Molecule-based transistors have attracted much attention due to their exclusive
      properties. Creation of a molecular transistor as well as engineering its
      structure have become one of the greatest aims of scientists. We have focused on
      the environmental dependent behavior of a DNA-templated transistor. Using the
      statistical distribution of the energy levels, we were able to distinguish the
      delocalized states of charge carriers and the transition between the localized
      and delocalized behaviors. On the other hand, we can determine the stability
      conditions of our quantum dynamical system. The results are verified by the
      inverse participation ratio method. Therefore, the most appropriate parameters
      for designing the DNA transistor are chosen. The DNA sequence is an important
      factor for its transport properties, but the results have shown that in the
      presence of the bath, the bath parameters are important, too. As is shown, it is
      possible that via the adjustment of bath parameters, one can design a
      conductivity channel for all nucleotide contents. Thus, one can engineer a DNA
      based transistor simply through the setting of only one parameter.

PMID- 29470079
TI  - Biocatalytic C-Glucosylation of Coumarins Using an Engineered C
      Glycosyltransferase.
AB  - The enzymatic synthesis of coumarin C-glucosides by an engineered C
      glycosyltransferase, MiCGTb-GAGM, was explored in vitro and in vivo. MiCGTb-GAGM
      exhibited a robust C-glucosylation capability toward structurally diverse
      coumarin derivatives. The whole-cell bioconversion of MiCGTb-GAGM was exploited
      for large-scale production of coumarin C-glucosides. Two C-glucosides exhibited
      potent SGLT2 inhibitory activities with IC50 values at 10-6 M. These findings
      provide cost-effective and practical synthetic strategies to generate
      structurally diverse and novel bioactive coumarin C-glycosides for drug
      discovery.

PMID- 29470080
TI  - Complex Air Pollution Mixtures Formed by Irradiation of Hydrocarbons Elicit an
      Array of Toxicological Responses.

PMID- 29470081
TI  - Rationally Designed Chiral Synthons Enabling Asymmetric Z- and E-Selective
      Vinylogous Aldol Reactions of Aldehydes.
AB  - In a conceptually different approach, highly stereoselective 2-oxonia-Cope
      rearrangement reactions between rationally designed nonracemic vinylogous
      aldolation synthons and aldehydes are described to provide delta-hydroxy
      alpha,beta-unsaturated esters with excellent enantioselectivities and, for the
      first time, unprecedented Z- and E-selectivities without the regioselectivity
      issue.

PMID- 29470082
TI  - Highly Enantioselective [5 + 2] Annulations through Cooperative N-Heterocyclic
      Carbene (NHC) Organocatalysis and Palladium Catalysis.
AB  - The highly enantioselective [5 + 2] annulation of enals with vinylethylene
      carbonates through a cooperative N-heterocyclic carbene (NHC)/Pd catalytic system
      is reported. The use of a bidentate phosphine ligand was crucial to prevent
      coordination of the NHC organocatalyst to the active Pd catalyst. The
      complementary and matched combination of the chiral NHC catalyst and chiral
      phosphine ligand promotes high levels of both reactivity and enantioselectivity
      (mostly >=99% ee).

PMID- 29470083
TI  - High-Temperature Isomerization of Benzenoid Polycyclic Aromatic Hydrocarbons.
      Analysis through the Bent Bond and Antiperiplanar Hypothesis Orbital Model.
AB  - L. T. Scott has discovered the 1,2-swapping of carbon and hydrogen atoms which is
      known to take place on benzenoid aromatics (up to ~1000  degrees C range). For
      example, 13C-1-naphthalene is specifically converted to 13C-2-naphthalene, and
      there is evidence that this occurs through the formation of benzofulvene and a
      naphthalene-carbene intermediate. Application of the bent bond/antiperiplanar
      hypothesis leads to the postulate that higher in energy pyramidal singlet
      diradical intermediates can be used to propose a mechanism that rationalizes
      various atom rearrangements on benzenoid aromatics and related isomeric
      compounds.

PMID- 29470084
TI  - Synthesis of High Relaxivity Gadolinium AAZTA Tetramers as Building Blocks for
      Bioconjugation.
AB  - Molecular imaging requires the specific accumulation of contrast agents at the
      target. To exploit the superb resolution of MRI for applications in molecular
      imaging, gadolinium chelates, as the MRI contrast agents (CA), have to be
      conjugated to a specific vector able to recognize the epitope of interest.
      Several Gd(III)-chelates can be chemically linked to the same binding vector in
      order to deliver multiple copies of the CA (multimers) in a single targeting
      event thus increasing the sensitivity of the molecular probe. Herein three novel
      bifunctional agents, carrying one functional group for the bioconjugation to
      targeting vectors and four Gd(III)-AAZTA chelate functions for MRI contrast
      enhancement (AAZTA = 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid), are
      reported. The relaxivity in the tetrameric derivatives is 16.4 +/- 0.2 mMGd-1 s-1
      at 21.5 MHz and 25  degrees C, being 2.4-fold higher than that of parent,
      monomeric Gd(III)-AAZTA. These compounds can be used as versatile building blocks
      to insert preformed, high relaxivity, and high density Gd-centers to biological
      targeting vectors. As an example, we describe the use of these bifunctional
      Gd(III)-chelates to label a fibrin-targeting peptide.

PMID- 29470085
TI  - Origins of the Endo and Exo Selectivities in Cyclopropenone, Iminocyclopropene,
      and Triafulvene Diels-Alder Cycloadditions.
AB  - The endo and exo stereoselectivities of Diels-Alder reactions of cyclopropenone,
      iminocyclopropene, and substituted triafulvenes with butadiene were rationalized
      using density functional theory calculations. When cyclopropenone is the
      dienophile, there is a 1.8 kcal/mol preference for the exo cycloaddition with
      butadiene, while the reaction of 3-difluoromethylene triafulvene with butadiene
      favors the endo cycloaddition by 2.8 kcal/mol. The influence of charge transfer
      and secondary orbital interactions on the stereoselectivity of Diels-Alder
      reactions involving triafulvenes and heteroanalogs is discussed. The predicted
      stereoselectivity correlates with both the charge and highest occupied molecular
      orbital (HOMO) coefficient at the C3 carbon of the triafulvene motif.

PMID- 29470086
TI  - Computational Study on N-N Homolytic Bond Dissociation Enthalpies of Hydrazine
      Derivatives.
AB  - The hydrazine derivatives have been regarded as the important building blocks in
      organic chemistry for the synthesis of organic N-containing compounds. It is
      important to understand the structure-activity relationship of the thermodynamics
      of N-N bonds, in particular, their strength as measured by using the homolytic
      bond dissociation enthalpies (BDEs). We calculated the N-N BDEs of 13
      organonitrogen compounds by eight composite high-level ab initio methods
      including G3, G3B3, G4, G4MP2, CBS-QB3, ROCBS-QB3, CBS-Q, and CBS-APNO. Then 25
      density functional theory (DFT) methods were selected for calculating the N-N
      BDEs of 58 organonitrogen compounds. The M05-2X method can provide the most
      accurate results with the smallest root-mean-square error (RMSE) of 8.9 kJ/mol.
      Subsequently, the N-N BDE predictions of different hydrazine derivatives
      including cycloalkylhydrazines, N-heterocyclic hydrazines, arylhydrazines, and
      hydrazides as well as the substituent effects were investigated in detail by
      using the M05-2X method. In addition, the analysis including the natural bond
      orbital (NBO) as well as the energies of frontier orbitals were performed in
      order to further understand the essence of the N-N BDE change patterns.

PMID- 29470087
TI  - Nature of Large Temporal Fluctuations of Hydrogen Transfer Rates in Single
      Molecules.
AB  - Double hydrogen transfer was monitored in single molecules of parent porphycene
      and its tetra- t-butyl derivative using confocal fluorescence microscopy. The
      molecules have been embedded in a polymer matrix. Under such conditions, a
      significant fraction of the population reveals a huge decrease of the
      tautomerization rate with respect to the value obtained from ensemble studies in
      solution. This effect is explained by a model that assumes that the rate is
      determined by the reorganization coordinate that involves slow relaxation of the
      polymer matrix. The model provides indirect evidence for the dominant role of
      tunneling. It is proposed that tautomerization in single molecules of the
      porphycene family can be used to probe polymer relaxation dynamics on the time
      scale ranging from picoseconds to minutes.

PMID- 29470088
TI  - Total Synthesis and Stereochemical Revision of Stereocalpin A: Mirror-Image
      Approach for Stereochemical Assignments of the Peptide-Polyketide Macrocycle.
AB  - Stereocalpin A is a cyclic depsipeptide with cytotoxic activity isolated from the
      Antarctic lichen Stereocaulon alpinum. Although a number of synthetic
      investigations of the unprecedented 12-membered macrocycle of stereocalpin A with
      a dipeptide segment and a polyketide substructure have been conducted, the
      configurational assignment has not been completed. In this study, we achieved the
      first total synthesis and stereochemical revision of stereocalpin A. To
      facilitate the comprehensive assessment of eight possible stereocalpin A isomers,
      four stereoisomers of polyketide precursors were conjugated with l-Phe-l-MePhe
      and d-Phe-d-MePhe dipeptides (MePhe: N-methylphenylalanine) to provide four
      possible isomers and four mirror-image structures of the remaining isomers,
      respectively. The comparative NMR analysis of a series of stereoisomers revealed
      that stereocalpin A possesses 2 R,4 S,5 R-configurations, which is unique among
      the related 12-membered hybrid peptide-polyketide natural products reported
      recently. The NOE correlations in the polyketide substructure of stereocalpin A
      were also retrospectively analyzed among the eight possible stereoisomers.

PMID- 29470089
TI  - Toward Hyperpolarization of Oil Molecules via Single Nitrogen Vacancy Centers in
      Diamond.
AB  - Efficient polarization of organic molecules is of extraordinary relevance when
      performing nuclear magnetic resonance (NMR) and imaging. Commercially available
      routes to dynamical nuclear polarization (DNP) work at extremely low
      temperatures, relying on the solidification of organic samples and thus bringing
      the molecules out of their ambient thermal conditions. In this work, we
      investigate polarization transfer from optically pumped nitrogen vacancy centers
      in diamond to external molecules at room temperature. This polarization transfer
      is described by both an extensive analytical analysis and numerical simulations
      based on spin bath bosonization and is supported by experimental data in
      excellent agreement. These results set the route to hyperpolarization of
      diffusive molecules in different scenarios and consequently, due to an increased
      signal, to high-resolution NMR.

PMID- 29470090
TI  - Engineering Interfacial Processes at Mini-Micro-Nano Scales Using Sessile Droplet
      Architecture.
AB  - Evaporating sessile functional droplets act as the fundamental building block
      that controls the cumulative outcome of many industrial and biological
      applications such as surface patterning, 3D printing, photonic crystals, and DNA
      sequencing, to name a few. Additionally, a drying single sessile droplet forms a
      high-throughput processing technique using low material volume which is
      especially suitable for medical diagnosis. A sessile droplet also provides an
      elementary platform to study and analyze fundamental interfacial processes at
      various length scales ranging from macroscopically observable wetting and
      evaporation to microfluidic transport to interparticle forces operating at a
      nanometric length scale. As an example, to ascertain the quality of 3D printing
      we must understand the fundamental interfacial processes at the droplet scale. In
      this article, we review the coupled physics of evaporation flow-contact-line
      driven particle transport in sessile colloidal droplets and provide methodologies
      to control the same. Through natural alterations in droplet vaporization, one can
      change the evaporative pattern and contact line dynamics leading to internal flow
      which will modulate the final particle assembly in a nontrivial fashion. We
      further show that control over particle transport can also be exerted by external
      stimuli which can be thermal, mechanical oscillations, vapor confinement (walled
      or a fellow droplet), or chemical (surfactant-induced) in nature. For example,
      significant augmentation of an otherwise evaporation-driven particle transport in
      sessile droplets can be brought about simply through controlled interfacial
      oscillations. The ability to control the final morphologies by manipulating the
      governing interfacial mechanisms in the precursor stages of droplet drying makes
      it perfectly suitable for fabrication-, mixing-, and diagnostic-based
      applications.

PMID- 29470091
TI  - Iron-Catalyzed Regiospecific Intermolecular Radical Cyclization of Anilines:
      Strategy for Assembly of 2,2-Disubstituted Indolines.
AB  - The first regiospecific catalytic intermolecular assembly of 2,2-disubstituted
      indolines has been developed. This protocol is based on a ligand and directing
      group free, iron-catalyzed radical [3 + 2] process, allowing efficient coupling
      of different N-sulfonylanilines with various alpha-substituted styrenes.
      Preliminary mechanistic studies elucidated the radical mechanism involving a
      reactive and versatile anilino radical and the importance of iron complex as a
      Lewis acid, rendering both the reactivity and regiospecificity of this
      transformation.

PMID- 29470092
TI  - The Stroop test as a measure of performance validity in adults clinically
      referred for neuropsychological assessment.
AB  - This study was designed to develop performance validity indicators embedded
      within the Delis-Kaplan Executive Function Systems (D-KEFS) version of the Stroop
      task. Archival data from a mixed clinical sample of 132 patients (50% male; MAge
      = 43.4; MEducation = 14.1) clinically referred for neuropsychological assessment
      were analyzed. Criterion measures included the Warrington Recognition Memory Test
      Words and 2 composites based on several independent validity indicators. An age
      corrected scaled score <=6 on any of the 4 trials reliably differentiated
      psychometrically defined credible and noncredible response sets with high
      specificity (.87-.94) and variable sensitivity (.34-.71). An inverted Stroop
      effect was less sensitive (.14-.29), but comparably specific (.85-90) to invalid
      performance. Aggregating the newly developed D-KEFS Stroop validity indicators
      further improved classification accuracy. Failing the validity cutoffs was
      unrelated to self-reported depression or anxiety. However, it was associated with
      elevated somatic symptom report. In addition to processing speed and executive
      function, the D-KEFS version of the Stroop task can function as a measure of
      performance validity. A multivariate approach to performance validity assessment
      is generally superior to univariate models. (PsycINFO Database Record

PMID- 29470093
TI  - Hemispheric asymmetries in setticlavio reading.
AB  - Musical setticlavio (literally, seven clefs) reading refers to the ability to
      read (i.e., to say aloud, without to sing) the musical note labels in the 7
      musical clefs. The present research report aims to investigate hemispheric
      asymmetries in such a basic musical ability, very poorly investigated in the
      domain of cognitive neurosciences. Sixty-three musicians underwent lateralized
      tachistoscopic presentation of musical notes on staves, 50% in the left and 50%
      in the right visual field, associated with each of the 7 musical clefs. The
      subjects' task was to pronounce as fast as possible the name of the presented
      note, taking into account the current clef symbol. Mixed directions of asymmetry
      with different involvements of the left and right hemisphere in each clef were
      observed. Whereas reading in the treble, bass, alto, tenor, and mezzosoprano clef
      showed no lateral asymmetries, a left hemisphere asymmetry was observed with the
      soprano clef and a right hemisphere asymmetry with the baritone clef. This effect
      was observed with accuracy but not with reaction time. These results suggest that
      there is not a univocal hemispheric balance in musical setticlavio reading,
      reflecting several possible underlying reading mechanisms. Moreover, inversely
      proportional results between performance (both accuracy and reaction time) and
      distance from the reference clef (treble) suggest that setticlavio reading is
      based on a spatial rather than verbal code. (PsycINFO Database Record

PMID- 29470094
TI  - Accuracy, User Acceptability, and Safety Evaluation for the FreeStyle Libre Flash
      Glucose Monitoring System When Used by Pregnant Women with Diabetes.
AB  - BACKGROUND: Accuracy of the FreeStyle LibreTM Flash Glucose Monitoring System has
      not been evaluated in pregnant women with diabetes. The aim of this study was to
      determine accuracy (compared to self-monitoring of blood glucose [SMBG]),
      clinical safety, and acceptability of the FreeStyle Libre System when used at
      home by this population. MATERIALS AND METHODS: Seventy-four participants, with
      type 1 (T1D, n = 24), type 2 (T2D, n = 11), or gestational (n = 39) diabetes,
      were enrolled across 13 sites (9 in United Kingdom, 4 in Austria). Average
      gestation was 26.6 +/- 6.8 weeks (mean +/- standard deviation), age was 30.5 +/-
      5.1 years, diabetes duration was 13.1 +/- 7.3 years for T1D and 3.2 +/- 2.5 years
      for T2D, and 49/74 (66.2%) used insulin to manage their diabetes. Sensors were
      worn for up to 14 days. Sensor glucose values (masked) were compared with
      capillary SMBG values (made at least 4 times/day). RESULTS: Clinical accuracy of
      sensor results versus SMBG results was demonstrated, with 88.1% and 99.8% of
      results within Zone A and Zones A and B of the Consensus Error Grid,
      respectively. Overall mean absolute relative difference was 11.8%. Sensor
      accuracy was unaffected by the type of diabetes, the stage of pregnancy, whether
      insulin was used, age or body mass index. User questionnaires indicated high
      levels of satisfaction with sensor wear, system use, and comparison to SMBG.
      There were no unanticipated device-related adverse events. CONCLUSIONS: Good
      agreement was demonstrated between the FreeStyle Libre System and SMBG. Accuracy
      of the system was unaffected by patient characteristics, indicating that the
      system is safe and accurate to use by pregnant women with diabetes.

PMID- 29470095
TI  - Subacromial Local Anesthetics Do Not Interfere With Rotator Cuff Healing After
      Arthroscopic Repair.
AB  - BACKGROUND: Subacromial pain pumps are used for analgesia after arthroscopic
      rotator cuff surgery. However, there is controversy about myotoxic or
      tendinotoxic effects of local anesthetics. HYPOTHESIS: Ropivacaine administered
      via a subacromial pain pump would have no adverse effect on rotator cuff tendon
      healing, fatty degeneration, strength, or functional outcomes after arthroscopic
      repair. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study
      continues follow-up of patients enrolled in the authors' 3 published prospective
      studies regarding pain control after arthroscopic rotator cuff repair. In total,
      118 patients who underwent rotator cuff repair and returned for evaluation at
      least 1 year postoperatively were divided into 3 groups: patients who received
      continuous subacromial ropivacaine infusion (group 1, n = 33), those who received
      patient-controlled subacromial ropivacaine infusion (group 2, n = 30), and those
      who received other pain control modalities (intravenous patient-controlled
      analgesia and/or interscalene block; group 3, n = 55). At least 1 year
      postoperatively, tendon healing and changes in global fatty degeneration index
      (GFDI) were estimated through computed tomographic arthrography, magnetic
      resonance imaging, or ultrasonography. Changes in isokinetic muscle performance
      test (IMPT) were calculated and functional outcomes evaluated, including visual
      analog scales (VASs) for pain and satisfaction, American Shoulder and Elbow
      Surgeons score, and Constant score. RESULTS: At final follow-up, there were no
      differences in pain VAS (group 1, 1.1 +/- 2.3; group 2, 1.3 +/- 1.9; group 3, 0.9
      +/- 1.7; P = .88), satisfaction VAS (group 1, 8.3 +/- 2.4; group 2, 8.7 +/- 1.5;
      group 3, 8.0 +/- 2.1; P = .64), American Shoulder and Elbow Surgeons score (group
      1, 79.5 +/- 10.5; group 2, 81.1 +/- 6.9; group 3, 75.7 +/- 7.6; P = .34), or
      Constant score (group 1, 81.8 +/- 8.7; group 2, 77.6 +/- 9.3; group 3, 78.2 +/-
      8.4; P = .31). Among the 3 groups, there were no significant differences in
      healing rates (group 1, 72.7%; group 2, 73.3%; group 3, 70.9%; P = .83) and no
      differences in changes of GFDI (group 1, 0.45; group 2, 0.62; group 3, 0.41; P =
      .79), and IMPT (abduction: group 1, 113.0%; group 2, 121.5%; group 3, 120.1%; P =
      .73; external rotation: group 1, 112.1%; group 2, 121.6%; group 3, 111.7%; P =
      .71; internal rotation: group 1, 118.2%; group 2, 118.0%; group 3, 118.1%; P =
      .95). When data were reanalyzed with 2 groups (group 1 + 2 vs group 3), there
      were no significant differences in functional scores, healing rates, or changes
      in GFDI and IMPT ( P > .05). CONCLUSION: Current data suggest that myotoxicity of
      subacromial ropivacaine administered via pain pump may be reversible or may not
      be so severe as to interfere with tendon healing and cause muscle degeneration
      and thus may not affect postoperative function.

PMID- 29470096
TI  - The psychometric properties, sensitivity and specificity of the geriatric anxiety
      inventory, hospital anxiety and depression scale, and rating anxiety in dementia
      scale in aged care residents.
AB  - OBJECTIVES: Limited research has been conducted into the identification of a
      valid and reliable screening measure for anxiety in aged care settings, despite
      it being one of the most common psychological conditions. This study aimed to
      determine an appropriate anxiety screening tool for aged care by comparing the
      reliability and validity of three commonly used measures and identifying specific
      cut-offs for the identification of generalized anxiety disorder (GAD). METHOD:
      One-hundred and eighty nursing home residents (M age = 85.39 years) completed the
      GAI, HADS-A, and RAID, along with a structured diagnostic interview. RESULTS:
      Twenty participants (11.1%) met DSM-5 criteria for GAD. All measures had good
      psychometric properties , although reliability estimates for the HADS-A were sub
      optimal. Privileging sensitivity , the GAI cut-off score of 9 gave sensitivity of
      90.0% and specificity of 86.3%; HADS-A cut-off of 6 gave sensitivity of 90.0% and
      specificity of 80.6%; and RAID cut-off of 11 gave sensitivity of 85.0% and
      specificity of 72.5%. CONCLUSION: While all three measures had adequate
      reliability, validity, and cut-scores with high levels of sensitivity and
      specificity to detect anxiety within aged care, the GAI was the most consistently
      reliable and valid measure for screening for GAD.

PMID- 29470097
TI  - A novel minimally invasive method of successful tissue glue injection in patients
      with iatrogenic pseudoaneurysm.
AB  - OBJECTIVE: To investigate the efficacy and safety of ultrasound-guided tissue
      glue injection for the treatment of iatrogenic femoral artery pseudoaneurysm.
      METHODS: The study comprised of nine patients with unsuccessful ultrasound-guided
      thrombin injection and one patient with rapidly progressing anemia. All patients
      had undergone recanalization procedures at least twice, including two subjects
      with a very rapidly enlarging pseudoaneurysm lobe or significant anemia. Tissue
      glue at a dose of 0.9 +/- 0.53 ml was injected under ultrasound guidance in each
      patient. RESULTS: Complete embolization was achieved in all patients. Follow-up
      ultrasound performed 24 h later as well as at 1 and 2 weeks did not show
      recurrent reperfusion of the pseudoaneurysm. CONCLUSION: Embolization of
      iatrogenic pseudoaneurysm using tissue glue seems to be an effective technique
      for the treatment of this complication. It might be considered as a treatment
      option in case of unsuccessful primary repair by means of thrombin injection
      orhemorrhagic shock due to rapid aneurysm progression. Advances in knowledge:
      Patients with multiple recanalizations and those with dynamically enlarging
      pseudoaneurysm or rapidly progressing anemia are at risk of life-threatening
      bleeding. An ultrasound-guided tissue glue injection, a novel method for the
      treatment of femoral artery pseudoaneurysm, might be considered as a treatment
      option especially in case of primary thrombin injection failure.

PMID- 29470098
TI  - Large datasets, logistics, sharing and workflow in screening.
AB  - Cancer screening initiatives exist around the world for different malignancies,
      most frequently breast, colorectal, and cervical cancer. A number of cancer
      registries exist to collect relevant data, but while these data may include
      imaging findings, they rarely, if ever, include actual images. Additionally, the
      data submitted to the registry are usually correlated with eventual cancer
      diagnoses and patient outcomes, rather than used with the individual's future
      screenings. Developing screening programs that allow for images to be submitted
      to a central location in addition to patient meta data and used for comparison to
      future screening exams would be very valuable in increasing access to care and
      ensuring that individuals are effectively screened at appropriate intervals. It
      would also change the way imaging results and additional patient data are
      correlated to eventual outcomes. However, it introduces logistical challenges
      surrounding secure storage and transmission of data to subsequent screening
      sites. In addition, in the absence of standardized protocols for screening,
      comparing current and prior imaging, especially from different equipment, can be
      challenging. Implementing a large-scale screening program with an image-enriched
      screening registry-effectively, an image-enriched electronic screening record
      also requires that incentives exist for screening sites, physicians, and patients
      to participate; to maximize coverage, participation may have to be supported by
      government agencies. Workflows will also have to be adjusted to support registry
      participation for all screening patients in an effort to create a large, robust
      data set that can be used for future screening efforts as well as research
      initiatives.center.

PMID- 29470099
TI  - Doses from cervical spine computed tomography (CT) examinations in the UK.
AB  - OBJECTIVE: To review doses to patients undergoing cervical spine CT examinations
      in the UK. METHODS: A data collection form was developed and distributed to
      medical physicists and radiographers via e-mail distribution lists. The form
      requested details of CT scanners, exposure protocols and patient dose index
      information. RESULTS: Data were received for 73 scanners. It was seen that 97% of
      scanners used automatic exposure control, and 60% of scanners used an iterative
      reconstruction technique for cervical spine examinations. The majority of scans
      were taken at 120 kV. The average patient dose indicators in terms of CT dose
      index (CTDIvol) ranged from 3.5 to 39.7 mGy (mean value 16.7 mGy), and for the
      DLP, ranged from 87 to 1030 mGy cm (mean value 379 mGy cm) as quoted for the
      standard 32 cm phantom. CONCLUSION: The rounded third quartile value of the mean
      dose distributions from this study were a CT dose index (CTDIvol) of 20 mGy and a
      dose-length product of 440 mGy cm as quoted for a 32 cm body phantom. These are
      significantly higher than those in the 2011 Public Health England CT dose survey
      when adjusted for phantom size. It is suggested that the existing national
      diagnostic reference levels for cervical spine CT should be amended, both with
      the new values and also to quote according to the 32 cm phantom. Advances in
      knowledge: Proposed new national diagnostic reference levels are presented for
      cervical spine CT examinations.

PMID- 29470100
TI  - Radiation repair models for clinical application.
AB  - A number of newly emerging clinical techniques involve non-conventional patterns
      of radiation delivery which require an appreciation of the role played by
      radiation repair phenomena. This review outlines the main models of radiation
      repair, focussing on those which are of greatest clinical usefulness and which
      may be incorporated into biologically effective dose assessments. The need to
      account for the apparent "slowing-down" of repair rates observed in some normal
      tissues is also examined, along with a comparison of the relative merits of the
      formulations which can be used to account for such phenomena. Jack Fowler brought
      valuable insight to the understanding of radiation repair processes and this
      article includes reference to his important contributions in this area.

PMID- 29470101
TI  - Ebselen Reversibly Inhibits Human Glutamate Dehydrogenase at the Catalytic Site.
AB  - Human glutamate dehydrogenase (GDH) plays an important role in neurological
      diseases, tumor metabolism, and hyperinsulinism-hyperammonemia syndrome (HHS).
      However, there are very few inhibitors known for human GDH. Recently, Ebselen was
      reported to crosslink with Escherichia coli GDH at the active site cysteine
      residue (Cys321), but the sequence alignment showed that the corresponding
      residue is Ala329 in human GDH. To investigate whether Ebselen could be an
      inhibitor for human GDH, we cloned and expressed an N-terminal His-tagged human
      GDH in E. coli. The recombinant human GDH enzyme showed expected properties such
      as adenosine diphosphate activation and nicotinamide adenine
      dinucleotide/nicotinamide adenine dinucleotide phosphate dual recognition.
      Further, we developed a 2-(3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H
      tetrazol-3-ium-5-yl) benzenesulfonate sodium salt (EZMTT)-based assay for human
      GDH, which was highly sensitive and is suitable for high-throughput screening for
      potent GDH inhibitors. In addition, ForteBio binding assays demonstrated that
      Ebselen is a reversible active site inhibitor for human GDH. Since Ebselen is a
      multifunctional organoselenium compound in Phase III clinical trials for
      inflammation, an Ebselen-based GDH inhibitor might be valuable for future drug
      discovery for HHS patients.

PMID- 29470102
TI  - What You Don't Notice Can Harm You: Age-Related Differences in Detecting
      Concurrent Visual, Auditory, and Tactile Cues.
AB  - Objective This research sought to determine whether people can perceive and
      process three nonredundant (and unrelated) signals in vision, hearing, and touch
      at the same time and how aging and concurrent task demands affect this ability.
      Background Multimodal displays have been shown to improve multitasking and
      attention management; however, their potential limitations are not well
      understood. The majority of studies on multimodal information presentation have
      focused on the processing of only two concurrent and, most often, redundant cues
      by younger participants. Method Two experiments were conducted in which younger
      and older adults detected and responded to a series of singles, pairs, and
      triplets of visual, auditory, and tactile cues in the absence (Experiment 1) and
      presence (Experiment 2) of an ongoing simulated driving task. Detection rates,
      response times, and driving task performance were measured. Results Compared to
      younger participants, older adults showed longer response times and higher error
      rates in response to cues/cue combinations. Older participants often missed the
      tactile cue when three cues were combined. They sometimes falsely reported the
      presence of a visual cue when presented with a pair of auditory and tactile
      signals. Driving performance suffered most in the presence of cue triplets.
      Conclusion People are more likely to miss information if more than two concurrent
      nonredundant signals are presented to different sensory channels. Application The
      findings from this work help inform the design of multimodal displays and ensure
      their usefulness across different age groups and in various application domains.

PMID- 29470103
TI  - An Approach to Children with Pulmonary Edema at High Altitude.
AB  - : Liptzin, Deborah R., Steven H. Abman, Ann Giesenhagen, and D. Dunbar Ivy. An
      approach to children with pulmonary edema at high altitude. High Alt Med Biol.
      19:91-98, 2018. INTRODUCTION: Diagnosis of high-altitude illness can be more
      challenging in children, especially those who are preverbal. Families often
      travel to high elevations for family vacations, either for skiing, hiking, and/or
      camping. They may present to their primary care providers looking for
      anticipatory guidance before travel or may follow-up after developing high
      altitude illness. High-altitude pulmonary edema (HAPE) can be fatal.
      OBSERVATIONS: There is no indication for HAPE prophylaxis in altitude naive
      children. Children may develop HAPE either when traveling from low altitude to
      high altitude for vacation (classic HAPE), when returning to high-altitude homes
      after travel to low altitude (reentry HAPE), or even with a respiratory illness
      at high altitude without any change in elevation (high-altitude resident
      pulmonary edema or HARPE). Children may be more susceptible to HAPE because of
      increased vascular reactivity, immature control of breathing, and increased
      frequency of respiratory illnesses. Children with HAPE warrant evaluation for
      underlying cardiopulmonary abnormalities, including structural heart disease and
      pulmonary hypertension. Treatment of HAPE includes supplemental oxygen and
      descent, but underlying cardiopulmonary disease may also help guide treatment and
      prevention. CONCLUSIONS AND RELEVANCE: Evaluation for structural heart disease
      and pulmonary hypertension should be considered in children with HAPE. Future
      studies should be done to elucidate the optimal strategies for prevention and
      treatment of HAPE and to better understand the development of HAPE in children.

PMID- 29470104
TI  - Association Between Utilization of Chiropractic Services for Treatment of Low
      Back Pain and Use of Prescription Opioids.
AB  - OBJECTIVE: Pain relief resulting from services delivered by doctors of
      chiropractic may allow patients to use lower or less frequent doses of opioids,
      leading to reduced risk of adverse effects. The objective of this investigation
      was to evaluate the association between utilization of chiropractic services and
      the use of prescription opioid medications. DESIGN: The authors used a
      retrospective cohort design to analyze health insurance claims data. SETTING: The
      data source was the all payer claims database administered by the State of New
      Hampshire. The authors chose New Hampshire because health claims data were
      readily available for research, and in 2015, New Hampshire had the second-highest
      age-adjusted rate of drug overdose deaths in the United States. SUBJECTS: The
      study population comprised New Hampshire residents aged 18-99 years, enrolled in
      a health plan, and with at least two clinical office visits within 90 days for a
      primary diagnosis of low-back pain. The authors excluded subjects with a
      diagnosis of cancer. OUTCOME MEASURES: The authors measured likelihood of opioid
      prescription fill among recipients of services delivered by doctors of
      chiropractic compared with nonrecipients. They also compared the cohorts with
      regard to rates of prescription fills for opioids and associated charges.
      RESULTS: The adjusted likelihood of filling a prescription for an opioid
      analgesic was 55% lower among recipients compared with nonrecipients (odds ratio
      0.45; 95% confidence interval 0.40-0.47; p < 0.0001). Average charges per person
      for opioid prescriptions were also significantly lower among recipients.
      CONCLUSIONS: Among New Hampshire adults with office visits for noncancer low-back
      pain, the likelihood of filling a prescription for an opioid analgesic was
      significantly lower for recipients of services delivered by doctors of
      chiropractic compared with nonrecipients. The underlying cause of this
      correlation remains unknown, indicating the need for further investigation.

PMID- 29470105
TI  - Diabetes Mellitus m-Health Applications: A Systematic Review of Features and
      Fundamentals.
AB  - BACKGROUND: The increasing number of diabetes mellitus (DM) m-health applications
      (apps) reveals a panorama of different approaches to the subject, demonstrating
      dynamism and heterogeneity. Available applications have various functions,
      capabilities, and data collection techniques. OBJECTIVE: We systematically
      reviewed the literature to identify and analyze studies regarding the diversity
      of applications aimed at DM monitoring and treatment. We aimed to investigate app
      functionalities, the basis for their design, and how they were tested. MATERIALS
      AND METHODS: We conducted a systematic literature review in Association for
      Computing Machinery (ACM), Institute of Electrical and Electronics Engineers
      (IEEE), ScienceDirect, Springer, and Medical Literature Analysis and Retrieval
      System Online (MEDLINE) databases. The search considered studies published until
      April 2017, without language restrictions. RESULTS: After removal of duplicates,
      679 studies were screened and assessed for eligibility, when 39 studies met the
      inclusion criteria. We present tables summarizing the functionalities, features,
      fundamental techniques, and methods. CONCLUSIONS: There is a variety of
      approaches used in the DM apps, with comprehensive, customizable, and adjusted
      functionalities for different purposes. Most apps are digital logbooks for
      collecting data on various daily tasks from DM treatment. The researchers are
      interested in guidelines of medical organizations, evaluations from health
      professionals and patients, and other methods to verify accuracy and reliability.

PMID- 29470106
TI  - A Dual-Process Perspective on How Sexual Experiences Shape Automatic Versus
      Explicit Relationship Satisfaction: Reply to Brody, Costa, Klapilova, and Weiss
      (2018).

PMID- 29470107
TI  - Leptospira Genomospecies and Sequence Type Prevalence in Small Mammal Populations
      in Germany.
AB  - Leptospirosis is a worldwide emerging infectious disease caused by zoonotic
      bacteria of the genus Leptospira. Numerous mammals, including domestic and
      companion animals, can be infected by Leptospira spp., but rodents and other
      small mammals are considered the main reservoir. The annual number of recorded
      human leptospirosis cases in Germany (2001-2016) was 25-166. Field fever
      outbreaks in strawberry pickers, due to infection with Leptospira kirschneri
      serovar Grippotyphosa, were reported in 2007 and 2014. To identify the most
      commonly occurring Leptospira genomospecies, sequence types (STs), and their
      small mammal host specificity, a monitoring study was performed during 2010-2014
      in four federal states of Germany. Initial screening of kidney tissues of 3,950
      animals by PCR targeting the lipl32 gene revealed 435 rodents of 6 species and 89
      shrews of three species positive for leptospiral DNA. PCR-based analyses resulted
      in the identification of the genomospecies L. kirschneri (62.7%), Leptospira
      interrogans (28.3%), and Leptospira borgpetersenii (9.0%), which are represented
      by four, one, and two STs, respectively. The average Leptospira prevalence was
      highest (~30%) in common voles (Microtus arvalis) and field voles (Microtus
      agrestis). Both species were exclusively infected with L. kirschneri. In
      contrast, in bank voles (Myodes glareolus) and yellow-necked mice (Apodemus
      flavicollis), DNA of all three genomospecies was detected, and in common shrews
      (Sorex araneus) DNA of L. kirschneri and L. borgpetersenii was identified. The
      association between individual infection status and demographic factors varied
      between species; infection status was always positively correlated to body
      weight. In conclusion, the study confirmed a broad geographical distribution of
      Leptospira in small mammals and suggested an important public health relevance of
      common and field voles as reservoirs of L. kirschneri. Furthermore, the
      investigations identified seasonal, habitat-related, as well as individual
      influences on Leptospira prevalence in small mammals that might impact public
      health.

PMID- 29470109
TI  - Determinants of the Intention of Senegal's Physicians to Use Telemedicine in
      Their Professional Activities.
AB  - BACKGROUND: In Senegal, physicians are unevenly distributed, leading to unequal
      access to healthcare in underserved areas. Telemedicine is seen as a potential
      means to address this problem. INTRODUCTION: Telemedicine's potential to improve
      access depends, in part, on physicians' intention to use the technology. In
      Senegal that intention is not well known. This study aimed to determine that
      intention and the factors that influence it. MATERIALS AND METHODS: We conducted
      a cross-sectional study between January and February 2015 with a random sample of
      168 physicians working in public hospitals and 153 in district health centers in
      Senegal. Data were collected using two questionnaires and analyzed using
      descriptive statistics, correlations, and linear regression. RESULTS: The
      intention to use telemedicine by physicians working in public hospitals and
      district health centers was moderate and was positively correlated with their
      attitude, subjective norm, and perceived behavioral control. The intention of the
      physicians working in public hospitals was also positively correlated with their
      region and status as contract employee, but negatively with their status as
      government employee. That of the physicians working in district health centers
      was negatively correlated with their age and years of practice. DISCUSSION: These
      results showed that, overall, the intention of Senegal's physicians to use
      telemedicine was moderate and could be improved by acting on factors related to
      their perceived behavioral control and other factors correlated with their
      intention. CONCLUSIONS: Physicians' intention to use telemedicine in Senegal is
      fair but could be improved by addressing the factors identified in this study.

PMID- 29470108
TI  - Application of 80-kVp scan and raw data-based iterative reconstruction for
      reduced iodine load abdominal-pelvic CT in patients at risk of contrast-induced
      nephropathy referred for oncological assessment: effects on radiation dose, image
      quality and renal function.
AB  - OBJECTIVE: To evaluate the image quality, radiation dose, and renal safety of
      contrast medium (CM)-reduced abdominal-pelvic CT combining 80-kVp and sinogram
      affirmed iterative reconstruction (SAFIRE) in patients with renal dysfunction for
      oncological assessment. METHODS: We included 45 patients with renal dysfunction
      (estimated glomerular filtration rate  <45 ml per min per 1.73 m2) who underwent
      reduced-CM abdominal-pelvic CT (360 mgI kg-1, 80-kVp, SAFIRE) for oncological
      assessment. Another 45 patients without renal dysfunction (estimated glomerular
      filtration rate >60 ml per lmin per 1.73 m2) who underwent standard oncological
      abdominal-pelvic CT (600 mgI kg-1, 120-kVp, filtered-back projection) were
      included as controls. CT attenuation, image noise, and contrast-to-noise ratio
      (CNR) were compared. Two observers performed subjective image analysis on a 4
      point scale. Size-specific dose estimate and renal function 1-3 months after CT
      were measured. RESULTS: The size-specific dose estimate and iodine load of 80-kVp
      protocol were 32 and 41%,, respectively, lower than of 120-kVp protocol (p <
      0.01). CT attenuation and contrast-to-noise ratio of parenchymal organs and
      vessels in 80-kVp images were significantly better than those of 120-kVp images
      (p < 0.05). There were no significant differences in quantitative or qualitative
      image noise or subjective overall quality (p > 0.05). No significant kidney
      injury associated with CM administration was observed. CONCLUSION: 80-kVp
      abdominal-pelvic CT with SAFIRE yields diagnostic image quality in oncology
      patients with renal dysfunction under substantially reduced iodine and radiation
      dose without renal safety concerns. Advances in knowledge: Using 80-kVp and
      SAFIRE allows for 40% iodine load and 32% radiation dose reduction for abdominal
      pelvic CT without compromising image quality and renal function in oncology
      patients at risk of contrast-induced nephropathy.

PMID- 29470110
TI  - Zika-Associated Microcephaly Epidemic and Birth Rate Reduction in Brazilian
      Cities.
AB  - OBJECTIVES: To estimate birth reduction potentially in response to Zika virus
      associated microcephaly among the 36 largest Brazilian cities. METHODS: We
      analyzed the number of live births per month on the basis of information on
      approximately 8.2 million births from all of Brazil's state capitals and cities
      that had more than 10 000 annual births. RESULTS: In the second half of 2016, the
      live birth rate was reduced by 7.78% (95% confidence interval [CI] = 6.64%,
      8.89%; P < .001). This reduction was correlated with the Zika virus-associated
      microcephaly rate. In the cities with the highest microcephaly rate in 2015 (> 1
      case per 1000 live births), the reduction in the live birth rate was 10.84% (95%
      CI = 8.58%, 13.04%). CONCLUSIONS: The birth rate in the largest Brazilian cities
      during the second half of 2016 was significantly reduced, which is potentially
      the effect of a birth control recommendation prompted by an epidemiological
      alert. Public Health Implications. The effects of population-based interventions
      should be weighed by considering the actual risk of disease and the
      sociodemographic impact of strategies such as birth control.

PMID- 29470111
TI  - Long-Acting Reversible Contraception Free of Charge, Method Initiation, and
      Abortion Rates in Finland.
AB  - OBJECTIVES: To evaluate whether a public program providing long-acting reversible
      contraceptive (LARC) methods free of charge increases the LARC initiation rate
      and reduces the unintended pregnancy rate in the general population. METHODS:
      Since 2013, all women in Vantaa, Finland, have been entitled to 1 LARC method
      free of charge. With time-series analysis between 2000 and 2015, we assessed
      whether this public program was associated with changes in steady-state mean
      rates of LARC initiation and abortions. RESULTS: The initiation rate of LARCs
      (1/1000 women) increased 2.2-fold from 1.9 to 4.2 after the intervention (P <
      .001). Concomitantly, the abortion rate (1/1000 women) declined by 16% from 1.1
      to 0.9 in the total sample (P < .001), by 36% from 1.3 to 0.8 among those aged 15
      to 19 years (P < .001), and by 14% from 2.0 to 1.7 among those aged 20 to 24
      years (P = .01). CONCLUSIONS: The LARC program was associated with increased
      uptake of LARC methods and fewer abortions in the population. Public Health
      Implications. Entitling the population to LARC methods free of charge is an
      effective means to reduce the unmet need of contraception and the need for
      abortion, especially among women younger than 25 years.

PMID- 29470112
TI  - Cumulative Prevalence of Maltreatment Among New Zealand Children, 1998-2015.
AB  - OBJECTIVES: To document, via linked administrative data, the cumulative
      prevalence among New Zealand children of notifications to child protective
      services (CPS), substantiated maltreatment cases, and out-of-home placements.
      METHODS: We followed all children born in New Zealand in 1998 until the end of
      2015 (an overall sample of 55 443 children). We determined the cumulative
      frequencies of notifications, substantiated maltreatment cases (by subtype), and
      first entries into foster care from birth through the age of 17 years. We also
      decomposed CPS involvement by gender. RESULTS: We found that almost 1 in 4
      children had been subject to at least 1 report to CPS at age 17 years (23.5%),
      and 9.7% had been a victim of substantiated abuse or neglect. We also found that
      3.1% had experienced out-of-home placements by age 17 years, with boys being more
      affected. CONCLUSIONS: Both notifications and substantiated child maltreatment
      are more common in New Zealand than is generally recognized, with the incidence
      of notifications higher than the incidence of medicated asthma among children and
      the prevalence of substantiations similar to the prevalence of obesity.

PMID- 29470113
TI  - Local-Level Adult Influenza and Pneumococcal Vaccination Disparities: Chicago,
      Illinois, 2015-2016.
AB  - OBJECTIVES: To investigate local-level adult influenza and pneumococcal
      vaccination disparities to inform targeted interventions. METHODS: Questions on
      influenza and pneumococcal vaccination uptake were included in a door-to-door
      community-based representative survey conducted in 10 Chicago, Illinois,
      neighborhoods in 2015 and 2016. A total of 1543 adults completed the survey,
      including 172 adults aged 65 years or older. We calculated adult influenza (>= 18
      years) and pneumococcal (>= 65 years) vaccination coverage by community area and
      respondent characteristics. RESULTS: We observed significant differences in
      pneumococcal vaccination coverage between community areas (range = 18%-91%).
      Influenza vaccination coverage differed by gender, age, insurance coverage,
      acculturation, and confidence or trust in physician. Non-Hispanic Blacks were
      more likely to be vaccinated when they had higher confidence or trust in their
      physician (45% vs 20%; P < .01). Mexicans who reported less acculturation were
      more likely to be vaccinated than were Mexicans who were more acculturated (41%
      vs 27%; P = .02). CONCLUSIONS: Striking disparities between neighborhoods and
      racial/ethnic groups in adult influenza and pneumococcal vaccination coverage
      highlight the need for improved local-level immunization coverage data.

PMID- 29470114
TI  - State Law Approaches to Facility Regulation of Abortion and Other Office
      Interventions.
AB  - OBJECTIVES: To compare the prevalence and characteristics of facility laws
      governing abortion provision specifically (targeted regulation of abortion
      providers [TRAP] laws); office-based surgeries, procedures, sedation or
      anesthesia (office interventions) generally (OBS laws); and other procedures
      specifically. METHODS: We conducted cross-sectional legal assessments of state
      facility laws for office interventions in effect as of August 1, 2016. We coded
      characteristics for each law and compared characteristics across categories of
      laws. RESULTS: TRAP laws (n = 55; in 34 states) were more prevalent than OBS laws
      (n = 25; in 25 states) or laws targeting other procedures (n = 1; in 1 state).
      TRAP laws often regulated facilities that would not be regulated under OBS laws
      (e.g., all TRAP laws, but only 2 OBS laws, applied regardless of sedation or
      anesthesia used). TRAP laws imposed more numerous and more stringent requirements
      than OBS laws. CONCLUSIONS: Many states regulate abortion-providing facilities
      differently, and more stringently, than facilities providing other office
      interventions. The Supreme Court's 2016 decision in Whole Woman's Health v
      Hellerstedt casts doubt on the legitimacy of that differential treatment.

PMID- 29470116
TI  - Mechanisms by Which Anti-Immigrant Stigma Exacerbates Racial/Ethnic Health
      Disparities.
AB  - Anti-immigrant rhetoric and political actions gained prominence and public
      support before, during, and after the 2016 presidential election. This anti
      immigrant political environment threatens to increase health disparities among
      undocumented persons, immigrant groups, and people of color. I discuss the
      mechanisms by which anti-immigrant stigma exacerbates racial/ethnic health
      disparities through increasing multilevel discrimination and stress, deportation
      and detention, and policies that limit health resources. I argue that the anti
      immigrant sociopolitical context is a social determinant of health that affects
      mostly communities of color, both immigrants and nonimmigrants. Public health has
      a moral obligation to consider how immigration policy is health policy and to be
      prepared to respond to worsening health disparities as a result of anti-immigrant
      racism.

PMID- 29470117
TI  - Adaptive Behavior of Sheltered Homeless Children in the French ENFAMS Survey.
AB  - OBJECTIVES: To describe the adaptive behaviors in a large sample of homeless
      children and identify factors associated with developmental delay. METHODS: Data
      were from a cross-sectional survey of 557 children younger than 6 years randomly
      sampled among homeless sheltered families in the Paris region, France (January
      May 2013). An interviewer and a psychologist conducted face-to-face interviews to
      collect information on sociodemographic and health characteristics. We assessed
      adaptive behaviors using the Vineland Adaptive Behavior Scales, second edition
      (VABS-II). RESULTS: The mean VABS-II composite score (SD) was 75.4 (12.0), and
      most participating children (80.9%) were considered developmentally delayed.
      Characteristics negatively associated with children's developmental score were
      age, birth in a country other than France, low birth weight, and past-year
      hospitalization. CONCLUSIONS: There is a high prevalence of developmental delays
      among children growing up homeless. Public Health Implications. Long-term
      integrated programs improving parenting and children's opportunities for
      stimulation and socialization should be developed in daycare centers, schools,
      shelters, and medical practices to minimize negative effects of early living
      conditions on children's development.

PMID- 29470115
TI  - Older Adults' Social Relationships and Health Care Utilization: A Systematic
      Review.
AB  - BACKGROUND: Deficiencies in older people's social relationships (including
      loneliness, social isolation, and low social support) have been implicated as a
      cause of premature mortality and increased morbidity. Whether they affect service
      use is unclear. OBJECTIVES: To determine whether social relationships are
      associated with older adults' use of health services, independently of health
      related needs. SEARCH METHODS: We searched 8 electronic databases (MEDLINE,
      Embase, CINAHL, Web of Science, PsycINFO, Scopus, the Cochrane Library, and the
      Centre for Reviews and Dissemination) for data published between 1983 and 2016.
      We also identified relevant sources from scanning the reference lists of included
      studies and review articles, contacting authors to identify additional studies,
      and searching the tables of contents of key journals. SELECTION CRITERIA: Studies
      met inclusion criteria if more than 50% of participants were older than 60 years
      or mean age was older than 60 years; they included a measure of social networks,
      received social support, or perceived support; and they reported quantitative
      data on the association between social relationships and older adults' health
      service utilization. DATA COLLECTION AND ANALYSIS: Two researchers independently
      screened studies for inclusion. They extracted data and appraised study quality
      by using standardized forms. In a narrative synthesis, we grouped the studies
      according to the outcome of interest (physician visits, hospital admissions,
      hospital readmissions, emergency department use, hospital length of stay,
      utilization of home- and community-based services, contact with general health
      services, and mental health service use) and the domain of social relationships
      covered (social networks, received social support, or perceived support). For
      each service type and social relationship domain, we assessed the strength of the
      evidence across studies according to the quantity and quality of studies and
      consistency of findings. MAIN RESULTS: The literature search retrieved 26 077
      citations, 126 of which met inclusion criteria. Data were reported across 226 678
      participants from 19 countries. We identified strong evidence of an association
      between weaker social relationships and increased rates of readmission to
      hospital (75% of high-quality studies reported evidence of an association in the
      same direction). In evidence of moderate strength, according to 2 high-quality
      and 3 medium-quality studies, smaller social networks were associated with longer
      hospital stays. When we considered received and perceived social support
      separately, they were not linked to health care use. Overall, the evidence did
      not indicate that older patients with weaker social relationships place greater
      demands on ambulatory care (including physician visits and community- or home
      based services) than warranted by their needs. AUTHORS' CONCLUSIONS: Current
      evidence does not support the view that, independently of health status, older
      patients with lower levels of social support place greater demands on ambulatory
      care. Future research on social relationships would benefit from a consensus on
      clinically relevant concepts to measure. Public Health Implications. Our findings
      are important for public health because they challenge the notion that lonely
      older adults are a burden on all health and social care services. In high-income
      countries, interventions aimed at reducing social isolation and loneliness are
      promoted as a means of preventing inappropriate service use. Our review cautions
      against assuming that reductions in care utilization can be achieved by
      intervening to strengthen social relationships.

PMID- 29470118
TI  - The Inverse Equity Hypothesis: Analyses of Institutional Deliveries in 286
      National Surveys.
AB  - OBJECTIVES: To test the inverse equity hypothesis, which postulates that new
      health interventions are initially adopted by the wealthy and thus increase
      inequalities-as population coverage increases, only the poorest will lag behind
      all other groups. METHODS: We analyzed the proportion of births occurring in a
      health facility by wealth quintile in 286 surveys from 89 low- and middle-income
      countries (1993-2015) and developed an inequality pattern index. Positive values
      indicate that inequality is driven by early adoption by the wealthy (top
      inequality), whereas negative values signal bottom inequality. RESULTS: Absolute
      inequalities were widest when national coverage was around 50%. At low national
      coverage levels, top inequality was evident with coverage in the wealthiest
      quintile taking off rapidly; at 60% or higher national coverage, bottom
      inequality became the predominant pattern, with the poorest quintile lagging
      behind. CONCLUSIONS: Policies need to be tailored to inequality patterns. When
      top inequalities are present, barriers that limit uptake by most of the
      population must be identified and addressed. When bottom inequalities exist,
      interventions must be targeted at specific subgroups that are left behind.

PMID- 29470119
TI  - Contraceptive Method Use During the Community-Wide HER Salt Lake Contraceptive
      Initiative.
AB  - OBJECTIVES: To describe a community-wide contraception initiative and assess
      changes in method use when cost and access barriers are removed in an environment
      with client-centered counseling. METHODS: HER Salt Lake is a prospective cohort
      study occurring during three 6-month periods (September 2015 through March 2017)
      and nested in a quasiexperimental observational study. The sample was women aged
      16 to 45 years receiving new contraceptive services at health centers in Salt
      Lake County, Utah. Following the control period, intervention 1 removed cost and
      ensured staffing and pharmacy stocking; intervention 2 introduced targeted
      electronic outreach. We used logistic regression and interrupted time series
      regression analyses to assess impact. RESULTS: New contraceptive services were
      provided to 4107 clients in the control period, 3995 in intervention 1, and 3407
      in intervention 2. The odds of getting an intrauterine device or implant
      increased 1.6 times (95% confidence interval [CI] = 1.5, 1.6) during intervention
      1 and 2.5 times (95% CI = 2.2, 2.8) during intervention 2, relative to the
      control period. Time series analysis demonstrated that participating health
      centers placed an additional 59 intrauterine devices and implants on average per
      month (95% CI = 13, 105) after intervention 1. CONCLUSIONS: Removing client cost
      and increasing clinic capacity was associated with shifts in contraceptive method
      mix in an environment with client-centered counseling; targeted electronic
      outreach further augmented these results.

PMID- 29470120
TI  - Racial/Ethnic Variation in the Impact of the Affordable Care Act on Insurance
      Coverage and Access Among Young Adults.
AB  - OBJECTIVES: To examine the impact of the Affordable Care Act's (ACA's) 2010
      parental insurance coverage extension to young adults aged 19 to 25 years on
      health insurance coverage and access to care, including racial/ethnic
      disparities. METHODS: We pooled data from the Behavioral Risk Factor Surveillance
      System for the periods 2007 to 2009 and 2011 to 2013 (n = 402 777). We
      constructed quasiexperimental difference-in-differences models in which adults
      aged 26 to 35 years served as a control group. Multivariable statistical models
      controlled for covariates guided by the Andersen model for health care
      utilization. RESULTS: On average, insurance rates among young adults increased
      6.12 percentage points after ACA implementation (P < .001). All racial/ethnic
      groups experienced increases in coverage. However, the impact varied by
      race/ethnicity and was largest for Whites. Young adults had a 2.61 percentage
      point (P < .001) decrease in experiencing barriers to health care because of cost
      issues after the ACA, with variation by race/ethnicity. CONCLUSIONS: The ACA's
      expansion had a significant positive effect for young adults acquiring health
      insurance and reducing cost-related barriers to accessing health care. However,
      racial/ethnic disparities in coverage and access persist. Public Health
      Implications. Policies not dependent on parental insurance could further increase
      access and reduce disparities.

PMID- 29470121
TI  - Disparities in Distribution of Particulate Matter Emission Sources by Race and
      Poverty Status.
AB  - OBJECTIVES: To quantify nationwide disparities in the location of particulate
      matter (PM)-emitting facilities by the characteristics of the surrounding
      residential population and to illustrate various spatial scales at which to
      consider such disparities. METHODS: We assigned facilities emitting PM in the
      2011 National Emissions Inventory to nearby block groups across the 2009 to 2013
      American Community Survey population. We calculated the burden from these
      emissions for racial/ethnic groups and by poverty status. We quantified
      disparities nationally and for each state and county in the country. RESULTS: For
      PM of 2.5 micrometers in diameter or less, those in poverty had 1.35 times higher
      burden than did the overall population, and non-Whites had 1.28 times higher
      burden. Blacks, specifically, had 1.54 times higher burden than did the overall
      population. These patterns were relatively unaffected by sensitivity analyses,
      and disparities held not only nationally but within most states and counties as
      well. CONCLUSIONS: Disparities in burden from PM-emitting facilities exist at
      multiple geographic scales. Disparities for Blacks are more pronounced than are
      disparities on the basis of poverty status. Strictly socioeconomic considerations
      may be insufficient to reduce PM burdens equitably across populations.

PMID- 29470122
TI  - A Qualitative Comparative Analysis of Combined State Health Policies Related to
      Human Papillomavirus Vaccine Uptake in the United States.
AB  - OBJECTIVES: To examine how combinations of state policies, rather than single
      policies, are related to uptake of human papillomavirus (HPV) vaccine. METHODS:
      Using publicly available records and the literature, we characterized policies
      for each US state and Washington, DC, in 2015 (n = 51), including (1) Medicaid
      expansion, (2) policies permitting HPV vaccination in pharmacies, (3) school
      entry requirements, (4) classroom sex education mandates, and (5) parental
      education mandates. Using qualitative comparative analysis, we identified which
      existing combinations of these policies were necessary and sufficient for high
      HPV vaccine initiation among adolescents, with National Immunization Survey-Teen
      data. RESULTS: No single policy was necessary or sufficient for high HPV vaccine
      uptake; however, 1 set of policies had consistently high HPV vaccine uptake:
      adoption of all policies except parental education mandates (girls: consistency =
      1.00, coverage = 0.07; boys: consistency = 0.99, coverage = 0.08). CONCLUSIONS:
      We identified a set of polices related to high HPV vaccine uptake. Future studies
      should examine how these policies and others, individually and in combination,
      are associated with HPV vaccine uptake. Public Health Implications. This study
      provides insight into what sets of policies are consistently related to high HPV
      vaccine uptake.

PMID- 29470123
TI  - Trends in Secondary Schools' Practices to Support Lesbian, Gay, Bisexual,
      Transgender, and Questioning Students, 2008-2014.
AB  - OBJECTIVES: To examine trends in the percentage of US secondary schools that
      implemented practices related to the support of lesbian, gay, bisexual,
      transgender, and questioning (LGBTQ) students. METHODS: This analysis used data
      from 4 cycles (2008-2014) of School Health Profiles, a surveillance system that
      provides results representative of secondary schools in each state. Each school
      completed 2 self-administered questionnaires (principal and teacher) per cycle.
      We used logistic regression models to examine linear trends. RESULTS: Of 8
      examined practices to support LGBTQ youths, only 1-identifying safe spaces for
      LGBTQ youths-increased in most states (72%) from 2010 to 2014. Among the
      remaining 7, only 1-prohibiting harassment based on a student's perceived or
      actual sexual orientation or gender identity-had relatively high rates of
      adoption (a median of 90.3% of schools in 2014) across states. CONCLUSIONS: Many
      states have seen no change in the implementation of school practices associated
      with LGBTQ students' health and well-being.

PMID- 29470124
TI  - Storage Practices of US Gun Owners in 2016.
AB  - OBJECTIVES: To examine gun storage practices and factors influencing those
      practices among gun owners. METHODS: We conducted a nationally representative
      online survey of US gun owners (n = 1444) in 2016 to assess gun storage practices
      and attitudes, factors influencing storage practices, and groups that might
      effectively communicate regarding safe storage. We generated descriptive
      statistics by using cross-tabulations and used logistic regression to estimate
      characteristics that influenced safe storage practices. RESULTS: Forty-six
      percent of gun owners reported safely storing all of their guns. Factors
      associated with higher odds of reporting safe storage were having a child in the
      home (adjusted odds ratio [AOR] = 1.44; 95% confidence interval [CI] = 1.03,
      2.03), only owning handguns (AOR = 1.84; 95% CI = 1.24, 2.73), and reporting that
      storage decisions were influenced by a gun safety course (AOR = 2.05; 95% CI =
      1.54, 2.74) or discussions with family members (AOR = 1.39; 95% CI = 1.05, 1.86).
      Gun owners ranked law enforcement, hunting or outdoors groups, active-duty
      military, and the National Rifle Association as most effective in communicating
      safe storage practices. CONCLUSIONS: Public health campaigns to promote safe gun
      storage should consider partnering with groups that garner respect among gun
      owners for their experience with safe use of guns.

PMID- 29470126
TI  - Law Accommodating Nonmotorized Road Users and Pedestrian Fatalities in Florida,
      1975 to 2013.
AB  - OBJECTIVES: To examine the effect of Florida's adoption of Statute 335.065-a law
      requiring the routine accommodation of nonmotorized road users (i.e., a "Complete
      Streets" policy)-on pedestrian fatalities and to identify factors influencing its
      implementation. METHODS: We used a multimethod design (interrupted time-series
      quasi-experiment and interviews) to calculate Florida's pedestrian fatality rates
      from 1975 to 2013-39 quarters before and 117 quarters after adoption of the law.
      Using statistical models, we compared Florida with regional and national
      comparison groups. Semistructured interviews were conducted with 10 current and
      former Florida transportation professionals in 2015. RESULTS: Florida's
      pedestrian fatality rates decreased significantly-by at least 0.500% more each
      quarter-after Statute 335.065 was adopted, resulting in more than 3500 lives
      saved across 29 years. Interviewees described supports and challenges associated
      with implementing the law. CONCLUSIONS: Florida Statute 335.065 is associated
      with a 3-decade decrease in pedestrian fatalities. The study also reveals factors
      that influenced the implementation and effectiveness of the law. Public Health
      Implications. Transportation policies-particularly Complete Streets policies-can
      have significant, quantifiable impacts on population health. Multimethod designs
      are valuable approaches to policy evaluations.

PMID- 29470125
TI  - Prison Health Care Governance: Guaranteeing Clinical Independence.
AB  - Clinical independence is an essential component of good health care and health
      care professionalism, particularly in correctional settings (jails, prisons, and
      other places of detention), where the relationship between patients and
      caregivers is not based on free choice and where the punitive correctional
      setting can challenge optimal medical care. Independence for the delivery of
      health care services is defined by international standards as a critical element
      for quality health care in correctional settings, yet many correctional
      facilities do not meet these standards because of a lack of awareness, persisting
      legal regulations, contradictory terms of employment for health professionals, or
      current health care governance structures. We present recommendations for the
      implementation of independent health care in correctional settings.

PMID- 29470127
TI  - Telemedicine Physical Examination Utilizing a Consumer Device Demonstrates Poor
      Concordance with In-Person Physical Examination in Emergency Department Patients
      with Sore Throat: A Prospective Blinded Study.
AB  - BACKGROUND: Telemedicine allows patients to connect with healthcare providers
      remotely. It has recently expanded to evaluate low-acuity illnesses such as
      pharyngitis by using patients' personal communication devices. The purpose of our
      study was to compare the telemedicine-facilitated physical examination with an in
      person examination in emergency department (ED) patients with sore throat.
      MATERIALS AND METHODS: This was a prospective, observational, blinded diagnostic
      concordance study of patients being seen for sore throat in a 60,000-visit
      Midwestern academic ED. A telemedicine and a face-to-face examination were
      performed independently by two advanced practice providers (APP), blinded to the
      results of the other evaluator. The primary outcome was agreement on pharyngeal
      redness between the evaluators, with secondary outcomes of agreement and inter
      rater reliability on 14 other aspects of the pharyngeal physical examination. We
      also conducted a survey of patients and providers to evaluate perceptions and
      preferences for sore throat evaluation using telemedicine. RESULTS: Sixty-two
      patients were enrolled, with a median tonsil size of 1.0. Inter-rater agreement
      (kappa) for tonsil size was 0.394, which was worse than our predetermined
      concordance threshold. Other kappa values ranged from 0 to 0.434, and
      telemedicine was best for detecting abnormal coloration of the palate and tender
      superficial cervical lymph nodes (anterior structures), but poor for detecting
      abnormal submandibular lymph nodes or asymmetry of the posterior pharynx
      (posterior structures). In survey responses, telemedicine was judged easier to
      use and more comfortable for providers than patients; however, neither patients
      nor providers preferred in-person to telemedicine evaluation. CONCLUSION:
      Telemedicine exhibited poor agreement with the in-person physical examination on
      the primary outcome of tonsil size, but exhibited moderate agreement on
      coloration of the palate and cervical lymphadenopathy. Future work should better
      characterize the importance of the physical examination in treatment decisions
      for patients with sore throat and the use of telemedicine in avoiding in-person
      healthcare visits.

PMID- 29470128
TI  - Human Subcutaneous Tissue Response to Glucose Sensors: Macrophages Accumulation
      Impact on Sensor Accuracy.
AB  - BACKGROUND: Subcutaneous (s.c.) glucose sensors have become a key component in
      type 1 diabetes management. However, their usability is limited by the impact of
      foreign body response (FBR) on their duration, reliability, and accuracy. Our
      study gives the first description of human acute and subacute s.c. response to
      glucose sensors, showing the changes observed in the sensor surface, the
      inflammatory cells involved in the FBR and their relationship with sensor
      performance. METHODS: Twelve obese patients (seven type 2 diabetes) underwent two
      abdominal biopsies comprising the surrounding area where they had worn two
      glucose sensors: the first one inserted 7 days before and the second one 24 h
      before biopsy procedure. Samples were processed and studied to describe tissue
      changes by two independent pathologists (blind regarding sensor duration).
      Macrophages quantification was studied by immunohistochemistry methods in the
      area surrounding the sensor (CD68, CD163). Sensor surface changes were studied by
      scanning electron microscopy. Seven-day continuous glucose monitoring records
      were considered inaccurate when mean absolute relative difference was higher than
      10%. RESULTS: Pathologists were able to correctly classify all the biopsies
      regarding sensor duration. Acute response (24 h) was characterized by the
      presence of neutrophils while macrophages were the main cell involved in subacute
      inflammation. The number of macrophages around the insertion hole was higher for
      less accurate sensors compared with those performing more accurately (32.6 +/- 14
      vs. 10.6 +/- 1 cells/0.01 mm2; P < 0.05). CONCLUSION: The accumulation of
      macrophages at the sensor-tissue interface is related with decrease in accuracy
      of the glucose measure.

PMID- 29470131
TI  - Letters From Our ReadersTo: Editor, The Angle Orthodontist Re: Salivary leptin
      levels in normal weight and overweight individuals and their correlation with
      orthodontic tooth movement. By Tamizhmani Jayachandran, Bhadrinath Srinivasan,
      Sridevi Padmanabhan. Angle Orthod. 2017;87:739-744.

PMID- 29470132
TI  - Letters From Our ReadersTo: Editor, The Angle Orthodontist. Re: Salivary leptin
      levels in normal weight and overweight individuals and their correlation with
      orthodontic tooth movement. Tamizhmani Jayachandran, Bhadrinath Srinivasan,
      Sridevi Padmanabhan. The Angle Orthodontist. 2017; 87: 739-744.

PMID- 29470133
TI  - An Orthodontist's Data.

PMID- 29470134
TI  - The Effect of Aronia Berry on Type 1 Diabetes In Vivo and In Vitro.
AB  - The number of diabetic patients worldwide is increasing, and complications such
      as stroke and cardiovascular disease are becoming a serious cause of death.
      Diabetes mellitus is classified into two types according to the etiopathogenic
      mechanism and insulin dependence. Type 1 diabetes (T1D), an insulin-dependent
      diabetes mellitus, is caused by damage and destruction of pancreatic beta cells
      that produce insulin. It is a disease that is characterized by hyperglycemia and
      hypoinsulinemia. Aronia berry has been used as a medicinal food in Europe. Aronia
      contains a variety of ingredients such as polyphenols, anthocyanins, flavonoids,
      and tannins. Especially, anthocyanin content in aronia berry is known to be much
      higher than in other plants and berries. It is known for exerting antioxidant,
      anti-inflammation, and anti-aging effects. Therefore, this study was conducted to
      investigate the effects of aronia berry extract intake in multiple low-dose
      streptozotocin (STZ)-induced T1D and to confirm the functional properties of
      aronia berry. ICR mice (6-week male) were divided into four groups: control
      (normal control group), STZ (100 mg/kg of STZ-induced T1D group), AR 10 (STZ with
      oral administration of aronia 10 mg/kg), and AR 100 (STZ with oral administration
      of aronia 100 mg/kg). Afterward, STZ was injected in a single dose to induce T1D,
      and the extract was orally administered daily. Dietary intake and body weight
      were measured twice a week. We confirmed that aronia berry has the effect of
      decreasing the increase of blood glucose level and also has the protection effect
      of pancreas beta cell (RINm5F cell). This study confirms the anti-diabetic
      activity of aronia berry, and it can be expected to increase the utilization
      according to the results.

PMID- 29470135
TI  - Effects of Task Difficulty and Display Format on Automation Usage Strategy: A
      Workload Capacity Analysis.
AB  - Objective An experiment used workload capacity analysis to quantify automation
      usage strategy across different task difficulty and display format types in a
      speeded task. Background Workload capacity measures the efficiency of concurrent
      information processing and can serve as a gauge of automation usage strategy in
      speeded decision tasks. The present study used workload capacity analysis to
      investigate automation usage strategy while information display format and task
      difficulty were manipulated. Method Subjects performed a speeded judgment task
      assisted by an automated aid that issued decision cues at varying onset times.
      Response time distributions were converted to measures of workload capacity.
      Results Two variants of a workload capacity measure, CzOR and CzAND, gave
      evidence that operators moderated their own decision times both in anticipation
      of and following the arrival of the aid's diagnosis under difficult task
      conditions regardless of display format. Conclusion Assistance from an automated
      decision aid may cause operators to delay their own responses in a speeded
      decision task, producing joint response time distributions that are slower than
      optimal. Application Even when it renders its own judgments quickly and with high
      accuracy, an automated decision aid may slow responses from a user. Automation
      designers should consider the relative costs and benefits of response accuracy
      and time when choosing whether and how to implement an automated decision aid.

PMID- 29470137
TI  - Open Access: Is There a Predator at the Door?

PMID- 29470136
TI  - 15O-H2O PET/CT as a tool for the quantitative assessment of early post
      radiotherapy changes of heart perfusion in breast carcinoma patients.
AB  - OBJECTIVE: Studies examining radiation-induced heart toxicity in breast cancer
      patients are inconclusive. The aim of this study was to prospectively and
      quantitatively asses myocardial blood flow (MBF) with, for the first time, 15O
      H2O PET/CT as a marker of heart damage in irradiated breast cancer patients.
      METHODS: 15 breast cancer patients receiving intact breast or chest wall
      irradiation were included in the analysis (six with right-sided and nine with
      left-sided breast cancer). They underwent 15O-H2O PET/CT before radiotherapy (RT)
      and 2 and 8 months after RT. MBF was quantitatively assessed at rest and under
      stress conditions in 17 heart segments distinguished according to the American
      Ultrasound Association classification. Regional MBF values were derived in each
      of the coronary artery territories. RESULTS: MBF decreased in 53% and increased
      in 33% of cases 2 months after RT in both left-sided and right-sided breast
      cancer patients. Stress testing was more sensitive than at-rest testing,
      demonstrating decreased perfusion in the segments supplied by the left anterior
      descending coronary artery (LAD) [5.41 +/- 1.74 vs 4.52 +/- 1.82 ml (g*min)-1; p
      = 0.018], which persisted at 6 months [5.41 +/- 1.74 vs 4.40 +/- 1.38 ml (g*min)
      1; p = 0.032] and a decrease in global heart perfusion [5.14 +/- 1.49 vs 4.46 +/-
      1.73 ml (g*min)-1; p = 0.036]. A minimal radiation dose applied to the LAD
      correlated with MBF changes observed 2 months after RT (r = -0.57; p = 0.032).
      Radiological findings were not correlated with clinical symptoms of heart
      toxicity. CONCLUSION: 15O-H2O PET/CT is safe and effective for the early
      detection and quantitative analysis of subclinical post-RT changes in heart
      perfusion in breast cancer patients. The LV segments supplied by the LAD are the
      main site of MBF changes. A minimum radiation dose deposited in the LAD may be a
      predictor of radiation-induced heart toxicity. Advances in knowledge: This is the
      first time that 15O-H2O PET/CT has been used to assess MBF after RT and the first
      granular description of the distribution of blood flow changes after breast
      cancer RT.

PMID- 29470138
TI  - Tracking Nemo: Help Scientists Understand Zebrafish Behavior.
AB  - The advent of automated tracking software has significantly reduced the time
      required to record movement trajectories, thereby facilitating behavioral studies
      of zebrafish. However, results are substantially influenced by tracking errors,
      such as loss and misidentification of individuals. In this study, we present the
      development of an online citizen science platform, Tracking Nemo, to improve data
      accuracy on swimming trajectories of zebrafish groups. As an online extension of
      software for tracking the position of zebrafish from video recordings, Tracking
      Nemo offers volunteers the opportunity to contribute to science by manually
      correcting tracked trajectory data from their personal computers. Researchers can
      upload their videos that require human intervention for correcting and validating
      the data. Citizen scientists can monitor their contributions through a
      leaderboard system, which is designed to strengthen participant retention and
      contribution by tapping into intrinsic and extrinsic motivations. Tracking Nemo
      is expected to help scientists improve data accuracy through the involvement of
      citizen scientists, who, in turn, engage in an authentic research activity and
      learn more about the behavior of zebrafish.

PMID- 29470139
TI  - Microstructural investigation of masticatory muscles: a pre- and post-treatment
      diffusion tensor imaging study in a bruxism case.
AB  - We evaluated, by means of a non-invasive procedure based on MRI, the masticatory
      muscular microstructure in a 55-year-old-female patient affected by bruxism. The
      patient underwent MR examination before and after 1 month of splint therapy, when
      she mentioned the complete disappearance of all symptoms. By means of diffusion
      tensor imaging we observed changes at microstructural level of masticatory
      muscular complex. We conclude that diffusion tensor imaging may be a useful
      instrument both to perform panoramic reconstruction of the masticatory muscle
      complex and to investigate microstructural modifications related to the pain
      relief in bruxism.

PMID- 29470140
TI  - Simple and fast spectrophotometric determination of low levels of thiabendazole
      residues in fruit and vegetables after pre-concentration with ionic liquid phase
      microextraction.
AB  - There is a great importance of monitoring thiabendazole (TBZ) residues in fruits
      and vegetables to ensure food safety. Therefore, a new ionic liquid (IL) phase
      microextraction method using IL, 1-butyl-3-methylimidazoliumhexafluorophosphate
      [C4mim][PF6], as extracting solvent is proposed for simple and fast determination
      of low levels of TBZ in fruits and vegetables by spectrophotometry. The method is
      based on selective complex formation of TBZ with Cu(II) ions in presence of PF6-
      as counter ion at pH 5.5, and then microextraction of the complex into the fine
      micro-drops of IL phase. After optimisation of variables affecting
      microextraction efficiency, the analytical parameters of the method were
      determined by calibration curves. The method exhibits a linear relationship (0.3
      280 MUg L-1), low detection limit (0.1 MUg L-1), good intra- and inter-day
      precision (2.4-4.5% as RSDr%, 2.1-5.6% as RSDR%), good recovery (>=95.1-98.2%)
      and high sensitivity enhancement factor (150) by solvent-based calibration curve.
      It allows a detection limit of 0.24 MUg L-1 and a range of 0.8-250 MUg L-1 by the
      matrix-matched calibration curve. After validation, the method was successfully
      applied to the determination of TBZ residues with method quantification limits in
      fruit and vegetables of 2.0 and 2.5 ug kg-1 with and without adding
      polyvinylpyrrolidone (PVP-15) solution. Recoveries range from 85.5% to 98.2%
      after spiking (10, 50 and 100 ug kg-1, n: 3).

PMID- 29470141
TI  - Denial's Many Faces.

PMID- 29470142
TI  - Screening for Hepatitis B Virus Infection: Are We Asking the Right Questions?

PMID- 29470143
TI  - Tumor PIK3CA Genotype and Prognosis in Early-Stage Breast Cancer: A Pooled
      Analysis of Individual Patient Data.
AB  - Purpose Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (
      PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated
      their prognostic relevance by performing a pooled analysis of individual patient
      data. Patients and Methods Associations between PIK3CA status and
      clinicopathologic characteristics were tested by applying Cox regression models
      adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human
      epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive
      disease-free survival (IDFS) was the primary end point; distant disease-free
      survival (DDFS) and overall survival (OS) were also assessed, overall and by
      breast cancer subtypes. Results Data from 10,319 patients from 19 studies were
      included (median OS follow-up, 6.9 years); 1,787 patients (17%) received
      chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received
      both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations
      occurred in 32% of patients, with significant associations with ER positivity,
      increasing age, lower grade, and smaller size (all P < .001). Prevalence of
      PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2
      positive, and ER-positive/HER2-negative subtypes, respectively. In univariable
      analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI,
      0.71 to 0.84; P < .001), with evidence for a stronger effect in the first years
      of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P < .001; 5 to 10
      years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); > 10 years: (HR, 1.15; 95% CI,
      0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA
      genotype remained significant for improved IDFS ( P = .043), but not for the DDFS
      and OS end points. Conclusion In this large pooled analysis, PIK3CA mutations
      were significantly associated with a better IDFS, DDFS, and OS, but had a lesser
      prognostic effect after adjustment for other prognostic factors.

PMID- 29470144
TI  - Effect of mono- and diglycerides on the digestion and absorption of lutein in
      lymph fistula rats.
AB  - Breast milk lutein is better absorbed by infants than lutein delivered in infant
      formula. Therefore, we wanted to better understand the possible absorption
      differences of lutein in breast milk vs. that in infant formula by determining
      its bioavailability after gastric administration and whether the intestinal
      absorption of lutein can be improved by using new delivery vehicles. Study 1
      compared the intestinal uptake,and the lymphatic and portal transport of lutein
      in conscious lymph fistula rats. Four groups of lymph- and portal vein-cannulated
      rats ( n = 8-10/group) were randomized to receive via gastric tube increasing
      doses (10, 20, 40, or 80 mg/kg) of 20% lutein in safflower oil (SO) suspension to
      assess whether there was a saturable level of lutein that could be absorbed and
      transported in lymph. Aliquots of hourly portal blood and lymph were taken for
      lutein and zeaxanthin analyses. The dose-response study showed that 20 mg/kg
      lutein was the saturable level of lymphatic lutein absorption with no lutein
      detected in portal circulation at any dosage level tested. Study 2 randomized
      five groups of lymph fistula rats ( n = 4-9/group) to receive 20 mg/kg lutein
      from either lutein in SO or lutein in four different mono- and diglyceride oils
      (MDGs). Gastric infusion of lutein suspended in MDG (20 mg/kg) significantly
      improved (71-211%, P < 0.05) lymphatic lutein output 2-6 h after lipid feeding
      vs. lutein in SO. Lymphatic zeaxanthin (10% of the lutein fed mixture) transport
      in both Study 1 and Study 2 followed that of lutein. We conclude that a mixture
      of MDGs helps solubilize lutein and facilitate gastrointestinal micelle
      formation, thus improving lymphatic lutein absorption compared with triglyceride
      oils. NEW & NOTEWORTHY This paper describes how lutein is digested and absorbed
      by the gastrointestinal tract by using the conscious lymph fistula rat model. Our
      dose-response study showed that absorption and lymphatic transport of lutein is a
      saturable process with no lutein detected in portal circulation at any dosage
      level tested. Our paper also provides insight into how this process can be
      improved by modifying the typical lipid mixtures carrying the lutein.

PMID- 29470145
TI  - Portal vein stenosis preconditioning of living donor liver in swine: early
      mechanisms of liver regeneration and gain of hepatic functional mass.
AB  - To reduce the morbidity and mortality risk for the donor in living donor liver
      transplantation (LDLT), we previously identified 20% left portal vein (LPV)
      stenosis as an effective preconditioning method to induce cell proliferation in
      the contralateral lobe without downstream ipsilateral atrophy. In this study, we
      report the pathways involved in the first hours after preconditioning and
      investigate the changes in liver volume and function. Fourteen pigs were used
      this study. Five pigs were used to study the genetic, cellular and molecular
      mechanisms set up in the early hours following the establishment of our
      preconditioning. The remaining nine pigs were equally divided into three groups:
      sham-operated animals, 20% LPV stenosis, and 100% LPV stenosis. Volumetric
      scanning and 99 mTc-Mebrofenin hepatobiliary scintigraphy were performed before
      preconditioning and 14 days after to study morphological and functional changes
      in the liver. We demonstrated that liver regeneration triggered by 20% LPV
      stenosis in the contralateral lobe involves TNF-alpha, IL-6, and inducible nitric
      oxide synthase 2 by means of STAT3 and hepatocyte growth factor. We confirmed
      that our preconditioning was responsible for an increase in the total liver
      volume. Finally, we demonstrated that this volumetric gain was associated with an
      increase in hepatic functional capacity. NEW & NOTEWORTHY We describe a new
      preconditioning method for major hepatectomy that is applicable to hepatectomy
      for donation. We identified 20% left portal vein stenosis as effective
      preconditioning that is capable of inducing cell proliferation in the
      contralateral lobe without the downstream ipsilateral atrophy. In this study, we
      report the pathways involved in the first hours following preconditioning, and we
      confirm that 20% left portal vein stenosis is responsible for an increase in the
      functional capacity and total liver volume in a porcine model.

PMID- 29470146
TI  - Toward an effective peripheral visceral analgesic: responding to the national
      opioid crisis.
AB  - This minireiew summarizes recent new developments in visceral analgesics. This
      promising field is important, as a new approach to address abdominal pain with
      peripheral visceral analgesics is considered a key approach to addressing the
      current opioid crisis. Some of the novel compounds address peripheral pain
      mechanisms through modulation of opioid receptors via biased ligands,
      nociceptin/orphanin FQ opioid peptide (NOP) receptor, or dual action on NOP and
      MU-opioid receptor, buprenorphine and morphiceptin analogs. Other compounds
      target nonopioid mechanisms, including cannabinoid (CB2), N-methyl-d-aspartate,
      calcitonin gene-related peptide, estrogen, and adenosine A2B receptors and
      transient receptor potential (TRP) channels (TRPV1, TRPV4, and TRPM8). Although
      current evidence is based predominantly on animal models of visceral pain, early
      human studies also support the evidence from the basic and animal research. This
      augurs well for the development of nonaddictive, visceral analgesics for
      treatment of chronic abdominal pain, an unmet clinical need.

PMID- 29470147
TI  - Repeated airway constrictions in mice do not alter respiratory function.
AB  - It is suggested that the frequent strain the airways undergo in asthma because of
      repeated airway smooth muscle (ASM)-mediated constrictions contributes to airway
      wall remodeling. However, the effects of repeated constrictions on airway
      remodeling, as well as the ensuing impact of this presumptive remodeling on
      respiratory mechanics, have never been investigated in subjects without asthma.
      In this study, we set out to determine whether repeated constrictions lead to
      features that are reminiscent of asthma in mice without asthma. BALB/c mice were
      subjected to a 30-min constriction elicited by aerosolized methacholine every
      other day over 6 wk. Forty-eight hours after the last constriction, the mechanics
      of the respiratory system was evaluated at baseline and in response to
      incremental doses of nebulized methacholine with the flexiVent. The whole-lung
      lavages, the tracheas, and the lungs were also collected to evaluate
      inflammation, the contractile capacity of ASM, and the structural components of
      the airway wall, respectively. The resistance and the compliance of the
      respiratory system, as well as the Newtonian resistance and the resistive and
      elastic properties of the lung tissue, were not affected by repeated
      constrictions, both at baseline and in response to methacholine. All the other
      examined features also remained unaltered, except the number of goblet cells in
      the epithelium and the number of macrophages in the whole-lung lavages, which
      both increased with repeated constrictions. This study demonstrates that, despite
      causing goblet cell hyperplasia and a mild macrophagic inflammation, repeated
      constrictions with methacholine do not lead to structural changes that adversely
      impact the physiology. NEW & NOTEWORTHY Repeated airway constrictions led to
      signs of remodeling that are typically observed in asthma, which neither altered
      respiratory mechanics nor the contractile capacity of airway smooth muscle. These
      findings shed light on a debate between those claiming that constrictions induce
      remodeling and those convinced that methacholine challenges are harmless. Insofar
      as our results with mice relate to humans, the findings indicate that repeated
      challenges with methacholine can be performed safely.

PMID- 29470148
TI  - Voluntary wheel running increases satellite cell abundance and improves recovery
      from disuse in gastrocnemius muscles from mice.
AB  - Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can
      induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel
      running, has been identified as a nondamaging rehabilitation therapy in rodents,
      but its effects on muscle function, morphology, and satellite cell activity after
      HSU are unclear. This study tested the hypothesis that low-impact wheel running
      would increase satellite cell proliferation and improve recovery of muscle
      structure and function after HSU in mice. Young adult male and female C57BL/6
      mice ( n = 6/group) were randomly placed into five groups. These included HSU
      without recovery (HSU), normal ambulatory recovery for 14 days after HSU
      (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR).
      Two control groups were used: nonsuspended mouse cage controls (Control) and
      voluntary wheel running controls (ControlWR). Satellite cell activation was
      evaluated by providing mice 5-bromo-2'-deoxyuridine (BrdU) in their drinking
      water. As expected, HSU significantly reduced in vivo maximal force, decreased in
      vivo fatigability, and decreased type I and IIa myosin heavy chain (MHC)
      abundance in plantarflexor muscles. HSU+WR mice significantly improved
      plantarflexor fatigue resistance, increased type I and IIa MHC abundance,
      increased fiber cross-sectional area, and increased the percentage of type I and
      IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a
      significantly greater percentage of BrdU-positive and Pax 7-positive nuclei
      inside muscle fibers and a greater MyoD-to-Pax 7 protein ratio compared with
      HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was
      elevated with reloading after HSU, but HSU+WR mice had lower levels of the
      inactive phosphorylated YAPserine127, which may have contributed to increased
      satellite cell activation with reloading after HSU. These results indicate that
      voluntary wheel running increased YAP signaling and satellite cell activity after
      HSU and this was associated with improved recovery. NEW & NOTEWORTHY Although
      satellite cell involvement in muscle remodeling has been challenged, the data in
      this study suggest that voluntary wheel running increased satellite cell activity
      and suppressed Yes-associated protein (YAP) protein relative to no wheel running
      and this was associated with improved muscle recovery of force, fatigue
      resistance, expression of type I myosin heavy chain, and greater fiber cross
      sectional area after disuse.

PMID- 29470150
TI  - Metrics of lung tissue heterogeneity depend on BMI but not age.
AB  - Altered parenchymal microstructure and complexity have been observed in older
      age. How to distinguish between healthy, expected changes and early signs of
      pathology remains poorly understood. An objective quantitative analysis of
      computed tomography imaging was conducted to compare mean lung density, tissue
      density distributions, and tissue heterogeneity in 16 subjects, 8 aged >60 yr who
      were gender and body mass index matched with 8 subjects aged <30 yr. Subjects had
      never been smokers, with no prior respiratory disease, and no radiologically
      identified abnormalities on computed tomography. Volume-controlled breath hold
      imaging acquired at 80% vital capacity (end inspiration) and 55% vital capacity
      (end expiration) were used for analysis. Mean lung density was not different
      between the age groups at end inspiration ( P = 0.806) but was larger in the
      younger group at end expiration (0.26 +/- 0.033 vs. 0.22 +/- 0.026, P = 0.008),
      as is expected due to increased air trapping in the older population. However,
      gravitational gradients of tissue density did not differ with age; the only
      difference in distribution of tissue density between the two age groups was a
      lower density in the apices of the older group at end expiration. The
      heterogeneity of the lung tissue assessed using two metrics showed significant
      differences between end inspiration and end expiration, no dependence on age, and
      a significant relationship with body mass index at both lung volumes when
      heterogeneity was calculated using quadtree decomposition but only at end
      expiration when using a fractal dimension. NEW & NOTEWORTHY Changes to lung
      tissue heterogeneity can be a normal part of aging but can also be an early
      indicator of disease. We use novel techniques, which have previously not been
      used on thoracic computed tomography imaging, to quantify lung tissue
      heterogeneity in young and old healthy subjects. Our results show no dependence
      on age but a significant correlation with body mass index.

PMID- 29470149
TI  - Chronic, complete cervical6-7 cord transection: distinct autonomic and cardiac
      deficits.
AB  - Spinal cord injury (SCI) resulting in tetraplegia is a devastating, life-changing
      insult causing paralysis and sensory impairment as well as distinct autonomic
      dysfunction that triggers compromised cardiovascular, bowel, bladder, and sexual
      activity. Life becomes a battle for independence as even routine bodily functions
      and the smallest activity of daily living become major challenges. Accordingly,
      there is a critical need for a chronic preclinical model of tetraplegia. This
      report addresses this critical need by comparing, for the first time, resting-,
      reflex-, and stress-induced cardiovascular, autonomic, and hormonal responses
      each week for 4 wk in 12 sham-operated intact rats and 12 rats with chronic,
      complete C6-7 spinal cord transection. Loss of supraspinal control to all
      sympathetic preganglionic neurons projecting to the heart and vasculature
      resulted in a profound bradycardia and hypotension, reduced cardiac sympathetic
      and parasympathetic tonus, reduced reflex- and stress-induced sympathetic
      responses, and reduced sympathetic support of blood pressure as well as enhanced
      reliance on angiotensin to maintain arterial blood pressure. Histological
      examination of the nucleus ambiguus and stellate ganglia supports the profound
      and distinct autonomic and cardiac deficits and reliance on angiotensin to
      maintain cardiovascular stability following chronic, complete cervical6-7 cord
      transection. NEW & NOTEWORTHY For the first time, resting-, reflex-, and stress
      induced cardiovascular, autonomic, and hormonal responses were studied in rats
      with chronic, complete C6-7 cord transection. Loss of supraspinal control of all
      sympathetic preganglionic neurons reduced cardiac sympathetic and parasympathetic
      tonus, reflex and stress-induced sympathetic responses, and sympathetic support
      of blood pressure as well as enhanced reliance on angiotensin to maintain
      arterial blood pressure. Histological examination supports the distinct deficits
      associated with cervical cord injury.

PMID- 29470151
TI  - Caffeine increases both total work performed above critical power and peripheral
      fatigue during a 4-km cycling time trial.
AB  - The link between total work performed above critical power (CP) and peripheral
      muscle fatigue during self-paced exercise is unknown. We investigated the
      influence of caffeine on the total work done above CP during a 4-km cycling time
      trial (TT) and the subsequent consequence on the development of central and
      peripheral fatigue. Nine cyclists performed three constant-load exercise trials
      to determine CP and two 4-km TTs ~75 min after oral caffeine (5 mg/kg) or
      cellulose (placebo) ingestion. Neuromuscular functions were assessed before and
      50 min after supplementation and 1 min after TT. Oral supplementation alone had
      no effect on neuromuscular function ( P > 0.05). Compared with placebo, caffeine
      increased mean power output (~4%, P = 0.01) and muscle recruitment (as inferred
      by EMG, ~17%, P = 0.01) and reduced the time to complete the TT (~2%, P = 0.01).
      Work performed above CP during the caffeine trial (16.7 +/- 2.1 kJ) was
      significantly higher than during the placebo (14.7 +/- 2.1 kJ, P = 0.01). End
      exercise decline in quadriceps twitch force (pre- to postexercise decrease in
      twitch force at 1 and 10 Hz) was more pronounced after caffeine compared with
      placebo (121 +/- 13 and 137 +/- 14 N vs. 146 +/- 13 and 156 +/- 11 N; P < 0.05).
      There was no effect of caffeine on central fatigue. In conclusion, caffeine
      increases muscle recruitment, which enables greater work performed above CP and
      higher end-exercise peripheral locomotor muscle fatigue. NEW & NOTEWORTHY The
      link between total work done above critical power and peripheral fatigue during a
      self-paced, high-intensity exercise is unclear. This study revealed that caffeine
      ingestion increases muscle recruitment, which enables greater work done above
      critical power and a greater degree of end-exercise decline in quadriceps twitch
      force during a 4-km cycling time trial. These findings suggest that caffeine
      increases performance at the expense of greater locomotor muscle fatigue.

PMID- 29470152
TI  - Linalyl acetate restores endothelial dysfunction and hemodynamic alterations in
      diabetic rats exposed to chronic immobilization stress.
AB  - Although stress is one of the risk factors of diabetes, few studies have assessed
      the effects of stress on diabetic rats. This study, therefore, analyzed
      differences in cardiovascular-related factors among control, nonstressed
      diabetic, and stressed diabetic rats as well as assessed the effects of linalyl
      acetate (LA) on stressed diabetic rats. Male Sprague-Dawley rats were subjected
      to immobilization stress throughout the experimental period, and diabetes was
      induced on day 15 by a single injection of streptozotocin. After confirming the
      induction of diabetes, stressed diabetic rats were administered LA (10 or 100
      mg/kg) or metformin (500 mg/kg) for the last 7 days. Compared with nonstressed
      diabetic rats, stressed diabetic rats had significantly lower body weight, body
      fat percentage, ACh-induced vasorelaxation, systolic blood pressure (SBP),
      diastolic blood pressure (DBP), heart rate (HR), and NF-kappaB expression as well
      as increased serum nitrite concentration. Although metformin increased serum
      insulin concentration significantly, 100 mg/kg LA showed only an increasing
      tendency. However, treatment with 100 mg/kg LA not only reduced serum glucose and
      NF-kappaB expression, but also restored ACh-induced vasorelaxation, SBP, DBP, HR,
      AMP-activated protein kinase expression, and serum nitrite almost to control
      levels. Importantly, 100 mg/kg LA was more effective than metformin in
      ameliorating serum glucose, endothelial nitric oxide synthase expression, HR, and
      serum nitrite. These findings suggest that chronic stress can aggravate
      endothelial dysfunction and hemodynamic alterations in diabetes and that LA may
      have potent therapeutic efficacy in diabetic patients with cardiovascular disease
      complications or chronic stress. NEW & NOTEWORTHY To our knowledge, this is the
      first study to assess the effects of linalyl acetate (LA) on cardiovascular
      related factors in diabetic rats exposed to chronic stress. Treatment with LA
      restored acetylcholine-induced vasorelaxation, blood pressure, heart rate, and
      AMP-activated protein kinase and serum nitrite levels. The present results
      suggest that LA may have potent therapeutic efficacy in diabetic patients with
      complications of cardiovascular disease or chronic stress.

PMID- 29470153
TI  - Structured Reporting of Multiphasic CT for Hepatocellular Carcinoma: Effect on
      Staging and Suitability for Transplant.
AB  - OBJECTIVE: The purpose of this study is to evaluate whether use of a standardized
      radiology report template would improve the ability of liver transplant surgeons
      to diagnose stage T2 hepatocellular carcinoma (HCC) and determine patient
      suitability to undergo orthotopic liver transplant (OLT). MATERIALS AND METHODS:
      In this retrospective study, a standardized template was devised, and its use was
      mandated for reporting of liver CT findings for patients with cirrhosis and HCC.
      Two surgeons analyzed 200 reports (100 before and 100 after template
      implementation) for descriptions of cirrhosis, portal hypertension, lesion
      enhancement characteristics, tumor thrombus, portal and superior mesenteric vein
      patency, and Organ Procurement Transplantation Network (OPTN) class. Ability to
      determine Milan criteria and surgeon satisfaction were also assessed. Data
      obtained before and after template implementation were statistically analyzed
      using the Cochran-Mantel-Haenszel test. RESULTS: Template implementation
      increased the percentage of reports documenting the presence or absence of portal
      hypertension (74% to 88% for surgeon 1 and 86% to 87% for surgeon 2; p = 0.042);
      lesion number (76% to 88% for surgeon 2 [no change for surgeon 1]; p = 0.038),
      size (95% to 96% for surgeon 1 and 82% to 93% for surgeon 2; p = 0.03), and
      enhancement (93% to 94% for surgeon 1 and 80% to 91% for surgeon 2; p = 0.049);
      presence of tumor thrombus (10% to 57% for surgeon 1 and 31% to 63% for surgeon
      2; p < 0.001); and OPTN class (8% to 82% for surgeon 1 and 2% to 81% for surgeon
      2; p < 0.001). The surgeons were significantly more able to determine the
      presence of T2 disease and qualification for exception points after
      implementation of the template (increasing from 80% to 94%; p = 0.025).
      Satisfaction with reports also improved (p < 0.0001). CONCLUSION: The reporting
      template improved determination of patient suitability to undergo transplant
      according to the Milan criteria.

PMID- 29470154
TI  - Unipedal Diagnostic Lymphangiography Followed by Sequential CT Examinations in
      Patients With Idiopathic Chyluria: A Retrospective Study.
AB  - OBJECTIVE: The objective of our study was to investigate the clinical value of
      diagnostic lymphangiography followed by sequential CT examinations in patients
      with idiopathic chyluria. MATERIALS AND METHODS: Thirty-six patients with
      idiopathic chyluria underwent unipedal diagnostic lymphangiography and then
      underwent sequential CT examinations. The examinations were reviewed separately
      by two radiologists. Abnormal distribution of contrast medium, lymphourinary
      leakages, and retrograde flow were noted, and the range and distribution of
      lymphatic vessel lesions were recorded. The stage of idiopathic chyluria based on
      CT findings and the stage based on clinical findings were compared. Therapeutic
      management and follow-up were recorded. Statistical analyses were performed.
      RESULTS: Compared with CT studies performed after lymphangiography, diagnostic
      lymphangiography showed a unique capability to depict lymphourinary leakages in
      three patients. Lymphourinary fistulas and abnormal dilated lymphatic vessels
      were found in and around kidney in all patients. CT depicted retrograde flow of
      lymph fluid in 47.2% of patients. The consistency in staging chyluria based on CT
      findings and clinical findings was fair (kappa = 0.455). Twenty-nine patients
      underwent conservative therapy, and seven underwent surgery. Surgical therapy was
      superior to conservative management (no recurrence, 85.7% of patients who
      underwent surgery vs 62.1% of patients who underwent conservative therapy; p =
      0.025). CONCLUSION: From assessing the drainage of contrast medium on unipedal
      diagnostic lymphangiography and the redistribution of contrast medium on
      sequential CT examinations, it is possible to detect the existence of
      lymphourinary fistulas, the precise location of lymphatic anomalies, the
      distribution of collateral lymphatic vessels, and hydrodynamic pressure
      abnormality in the lymph circulation in patients with idiopathic chyluria. CT
      staging of chyluria provides additional information that can be used to guide
      therapeutic management.

PMID- 29470155
TI  - Clinical Utility of Dual-Energy CT Analysis of Bone Marrow Edema in Acute Wrist
      Fractures.
AB  - OBJECTIVE: The purpose of this study is to determine the utility of dual-energy
      CT (DECT) for assessing carpal fractures and to obtain an attenuation value
      cutoff (in Hounsfield units) to identify bone marrow edema due to an acute carpal
      fracture. MATERIALS AND METHODS: In this retrospective study, 24 patients who
      presented with wrist fractures from September 3, 2014, through March 9, 2015,
      underwent imaging with DECT (80 and 140 kVp). Using the three-material
      decomposition algorithm specific for virtual noncalcium to construct images, two
      radiologists identified carpal fractures and associated bone marrow edema.
      Readers noted the attenuation at areas with and without bone marrow edema. The
      cutoff value was obtained by ROC analysis and was internally validated on 13
      separate patients with suspected wrist fractures. A p < 0.05 was considered
      statistically significant. RESULTS: CT attenuation was significantly higher in
      areas of bone marrow edema than in areas without it (p < 0.0001, t test). A
      cutoff of 5.90 HU allows detection of bone marrow edema associated with acute
      wrist fractures with 100% sensitivity and 99.5% specificity, compared with visual
      DECT interpretation. In the 13 validation cases, the cutoff of 5.90 HU identified
      bone marrow edema with 100% accuracy, compared with visual interpretation. Kappa
      values were 0.83 between the two readings by reader 1, and 0.73 and 0.96
      comparing the two readings of reader 1 with the reading by reader 2. CONCLUSION:
      DECT is a useful tool for identifying bone marrow edema in the setting of acute
      wrist fractures, providing an alternative to MRI. A cutoff value of 5.90 HU can
      be used for accurate diagnosis and exclusion of carpal fractures.

PMID- 29470156
TI  - JOURNAL CLUB: Evaluation of Diffusion Kurtosis Imaging of Stroke Lesion With
      Hemodynamic and Metabolic MRI in a Rodent Model of Acute Stroke.
AB  - OBJECTIVE: Diffusion kurtosis imaging (DKI) has emerged as a new acute stroke
      imaging approach, augmenting routine DWI. Although it has been shown that a
      diffusion lesion without kurtosis abnormality is more likely to recover after
      reperfusion, whereas a kurtosis lesion shows poor response, little is known about
      the underlying pathophysiologic profile of the kurtosis lesion versus the
      kurtosis lesion-diffusion lesion mismatch. MATERIALS AND METHODS: We performed
      multiparametric MRI, including arterial spin labeling, pH-sensitive amide proton
      transfer, and DKI, in a rodent model of acute stroke caused by embolic middle
      cerebral artery occlusion. Diffusion and kurtosis lesions were semiautomatically
      segmented, and multiparametric MRI indexes were compared among the kurtosis
      lesion, diffusion lesion, kurtosis lesion-diffusion lesion mismatch, and the
      contralateral normal tissue area. RESULTS: We confirmed a significant difference
      between diffusion lesion and kurtosis lesion volumes (mean [+/- SD] volume, 151
      +/- 65 vs 125 +/- 47 mm3; p < 0.05). Although ischemic lesions have significantly
      reduced cerebral blood flow compared with contralateral normal tissue, we did not
      find a significant difference in cerebral blood flow between the kurtosis lesion
      and the kurtosis lesion-diffusion lesion mismatch (mean cerebral blood flow, 0.53
      +/- 0.10 vs 0.47 +/- 0.14 mL/g of tissue per minute; p > 0.05). Of importance,
      the pH of the kurtosis lesion was significantly lower than that of the lesion
      mismatch (mean pH, 6.81 +/- 0.08 vs 6.89 +/- 0.09; p < 0.01). CONCLUSION: The
      present study confirms that DKI provides an expedient approach for refining the
      heterogeneous DWI lesion that is associated with graded metabolic derangement,
      which is promising for improving the infarction core definition and ultimately
      helping to guide stroke treatment.

PMID- 29470157
TI  - Solid Small Renal Mass Without Gross Fat: CT Criteria for Achieving Excellent
      Positive Predictive Value for Renal Cell Carcinoma.
AB  - OBJECTIVE: The purpose of this study was to evaluate CT criteria for achieving
      high positive predictive value (PPV) for renal cell carcinoma (RCC) in patients
      with solid small renal masses (SRMs) less than 4 cm without macroscopic fat.
      MATERIALS AND METHODS: One hundred fifty consecutive patients with a solid SRM
      without macroscopic fat (mean size +/- SD, 2.5 +/- 0.8 cm) who underwent CT
      including unenhanced, corticomedullary (CMP), and nephrographic phases (NP) were
      evaluated. Pathologically proven solid SRMs without macroscopic fat were
      classified into RCC (n = 131) and not RCC (n = 19). A "persistent low" sign was
      defined as a focal area or areas of low attenuation seen at the same location
      within the lesion on both CMP and NP imaging. Calcification, shape, and lesion
      attenuation on unenhanced CT were analyzed by two independent readers. RESULTS:
      PPV of CT criteria (calcification [criterion 1] or spherical shape, lower or
      equal attenuation, and persistent low sign [criterion 2]) for RCC was 98.3%
      (58/59) for reader 1 and 100% (53/53) for reader 2. Weighted kappa of interreader
      agreement was 1.000 for calcification, 0.966 of lower or equal attenuation, 0.834
      for spherical shape, 0.823 for persistent low sign, and 0.829 for CT criteria.
      CONCLUSION: Interpretation of CT allowed reproducible and excellent PPV for RCC.
      Current CT criteria may effectively shorten the management process for solid SRMs
      without macroscopic fat by reducing unnecessary biopsy for a substantial number
      of RCCs showing typical CT findings.

PMID- 29470158
TI  - The Clinical Significance of Osteophytes in Compartments of the Knee Joint With
      Normal Articular Cartilage.
AB  - OBJECTIVE: The purpose of this study is to determine whether marginal osteophytes
      in compartments with normal cartilage would be more frequently observed in knees
      with cartilage lesions and osteophytes in other compartments. MATERIALS AND
      METHODS: This retrospective study reviewed 500 consecutive knee MRI examinations
      performed within 6 months of arthroscopic knee surgery conducted for 497 patients
      with symptoms (289 male patients and 208 female patients; age range, 17-74 years;
      median age, 43 years). The highest grade of cartilage lesion detected at MRI and
      arthroscopy was recorded. Marginal osteophytes were graded on MRI with use of a
      standardized scoring system, with grade 0 denoting no osteophyte; grade 1, small
      osteophyte; grade 2, medium-size osteophyte; and grade 3, large osteophyte). The
      frequency of false-positive osteophytes, defined as osteophytes present in
      compartments (the patellofemoral, medial tibiofemoral, and lateral tibiofemoral
      compartments) with normal cartilage observed on MRI and arthroscopy, was
      calculated. The Goodman and Kruskal gamma statistic was used to test the
      association of osteophyte size between compartments. Logistic regression was used
      to test the association between osteophyte size and the severity of the cartilage
      lesions. RESULTS: Marginal osteophytes were seen in compartments with normal
      cartilage on MRI and arthroscopy in 60.5% of knees (75 of 124) with cartilage
      lesions and osteophytes in other compartments and accounted for all false
      positive grade 2 and grade 3 osteophytes. Marginal osteophytes were seen in 12.7%
      of knees (13 of 102) that had no cartilage lesions in any compartment on MRI or
      arthroscopy, and all of these were grade 1 osteophytes. The presence of larger
      sized osteophytes in the compartments with cartilage lesions was associated with
      the presence of larger sized osteophytes in the compartments with normal
      cartilage. More severe cartilage lesions were associated with larger osteophyte
      size. CONCLUSION: Compartments with marginal osteophytes and normal cartilage are
      commonly seen in knees that have other compartments with osteophytes and
      cartilage lesions.

PMID- 29470159
TI  - Central Metatarsalgia and Walking on Pebbles: Beyond Morton Neuroma.
AB  - OBJECTIVE: Central metatarsalgia relates to abnormalities of the second, third,
      and fourth metatarsals and their respective metatarsophalangeal joints. A variety
      of disorders present with central forefoot pain; they range from traumatic
      lesions (acute or chronic repetitive), inflammatory and infective disorders,
      nonneoplastic soft-tissue lesions, and benign tumors to malignant lesions.
      Patients often present with symptoms of localized pain in the forefoot that
      worsens on weight bearing (walking or running), which can be sharp or dull and
      often is perceived as a lump felt inside or underneath the foot and described as
      walking on a marble or pebbles. These patients are labeled as having central
      metatarsalgia and are further evaluated with ultrasound or MRI to establish a
      diagnosis. CONCLUSION: In this article, we review metatarsal and intermetatarsal
      lesions of the foot that present with central forefoot pain and a sensation of
      walking on pebbles, focusing on conditions mimicking Morton neuroma clinically or
      on imaging. We also briefly review some other plantar lesions and arthropathy
      that can present with awareness of lump underneath the foot.

PMID- 29470160
TI  - Contribution of 3-T Susceptibility-Weighted MRI to Detection of Intraarticular
      Hemosiderin Accumulation in Patients With Hemophilia.
AB  - OBJECTIVE: The purpose of this study was to assess the feasibility of 3-T
      susceptibility-weighted imaging (SWI) for detecting intraarticular hemosiderin
      accumulation in patients with hemophilia. SUBJECTS AND METHODS: Forty-one joints
      in 24 patients with hemophilia were imaged with conventional MRI and SWI
      sequences. Two experienced musculoskeletal radiologists and one general
      radiologist (reader 3) interpreted the images for hemosiderin accumulation. The
      final decision was determined in consensus by readers 1 and 2 using both
      conventional MRI and SWI sequences. The diagnostic consistencies of each MRI
      sequence with the reference and pairwise agreements between interpreters were
      assessed. RESULTS: For conventional MRI sequences, the diagnostic consistencies
      of the two experienced musculoskeletal radiologists with the reference were
      substantial (kappa = 0.63 and 0.62), whereas the consistency of the general
      radiologist with the reference was moderate (kappa = 0.47). The SWI
      interpretations of all readers had almost perfect agreement with the reference
      (kappa = 1, kappa = 1, kappa = 0.97). Interobserver agreement also improved at
      SWI interpretations. CONCLUSION: SWI contributes to more accurate grading of
      intraarticular hemosiderin accumulation than is achieved with conventional MRI
      sequences.

PMID- 29470161
TI  - The Child With Macrocephaly: Differential Diagnosis and Neuroimaging Findings.
AB  - OBJECTIVE: The purpose of this article is to offer a systematic approach to the
      imaging of children with macrocephaly and to illustrate key neuroimaging features
      of common and rare but important disorders. CONCLUSION: Macrocephaly is a common
      clinical finding in children. Increased volume of one of the intracranial
      compartments can enlarge the head either prenatally or postnatally while the
      cranial sutures are open. Imaging plays a central role in establishing a
      diagnosis and guiding management.

PMID- 29470162
TI  - Pulmonary Mucormycosis: Radiologic Features at Presentation and Over Time.
AB  - OBJECTIVE: Pulmonary mucormycosis is an aggressive opportunistic fungal
      infection. We set out to evaluate the CT and MRI features of pulmonary
      mucormycosis. MATERIALS AND METHODS: Through a search of the electronic medical
      record from 2007 to 2017, we identified 30 patients with definite or probable
      mucormycosis. Two radiologists reviewed the initial chest CT examinations for the
      presence of features including the "reverse halo" sign, large ground-glass halo,
      and peripheral lesion distribution. Additional CT and MRI studies were reviewed
      to evaluate evolution over time. RESULTS: The majority (67%) of patients had
      lesions with the reverse halo sign at some point in the disease course. A ground
      glass halo larger than the lesion was seen in 53% of patients. Notably, lesions
      had a peripheral predominance in 87% of cases. Through careful review of images,
      a perivascular ground-glass precursor lesion was identified in 20% of patients 1
      2 weeks before a consolidation developed. In five (17%) patients, CT showed a
      multifocal pneumonia appearance. Finally, MRI of two patients showed T2
      hypointense rims and central nonenhancement, a finding we refer to as the "black
      hole" sign. CONCLUSION: Large nodules or consolidations with an associated
      reverse halo sign or large perilesional ground-glass halos are common in
      mucormycosis. Lesions tend to show a peripheral predominance, and a perivascular
      ground-glass focus preceded nodular lesions in some cases. In some patients with
      severe disease, imaging features evolved to show a multifocal pneumonia pattern,
      and this pattern was associated with a high mortality rate.

PMID- 29470163
TI  - Abdominal Exploration in Neonates Using Transumbilical Exposure Compared with
      Transverse Laparotomies.
AB  - INTRODUCTION: The vertical transumbilical incision (TU) technique during neonatal
      abdominal exploration involves dissection and ligation of umbilical vessels,
      which allow access to all quadrants of the abdomen and complete bowel
      evisceration with minimal violation to the anterior abdominal wall. We compared
      patient characteristics and outcomes for neonates undergoing TU with standard
      transverse exploration. MATERIALS AND METHODS: A single-center retrospective
      review of neonates who underwent abdominal exploration between January 2010 and
      September 2015 was conducted after obtaining Institutional Review Board approval.
      Data included patient demographics, indication for operative intervention,
      operative details, complications, including incisional hernias, and long-term
      outcomes. RESULTS: There were 88 neonates under 4 months of age who underwent
      abdominal exploration, with a median age of 5.5 +/- 17 days and a median
      gestational age of 32.8 +/- 16 weeks. Exploration was emergent in 38 patients
      (43%) and 49 (56%) required ostomy formation. A transverse incision (TV) was used
      in 30 patients and a TU in 58 patients. Both groups had similar postoperative
      complication rates; 27 (47%) in the TU group and 11 (36%) in the TV group, P =
      .51. Median length of follow-up in the TU group was 5.1 +/- 18 months and 6.2 +/-
      16 months in the TV group, P = .48. The TU group had 4 incisional/umbilical
      hernias (7%), none have required repair. CONCLUSION: TUs for abdominal
      explorations in neonates have similar outcomes as the standard TV while
      preserving the integrity of the anterior abdominal wall.

PMID- 29470164
TI  - External Quality Assessment for Zika Virus Molecular Diagnostic Testing, Brazil.
AB  - We conducted an external quality assessment of Zika virus molecular diagnostic
      tests in Brazil using a new Zika virus standard. Of 15 laboratories, 73% showed
      limited sensitivity and specificity. Viral load estimates varied significantly.
      Continuous quality assurance is needed to adequately estimate risk for Zika virus
      associated disease and determine patient care.

PMID- 29470165
TI  - Multiple Introductions of Influenza A(H5N8) Virus into Poultry, Egypt, 2017.
AB  - After high mortality rates among commercial poultry were reported in Egypt in
      2017, we genetically characterized 4 distinct influenza A(H5N8) viruses isolated
      from poultry. Full-genome analysis indicated separate introductions of H5N8 clade
      2.3.4.4 reassortants from Europe and Asia into Egypt, which poses a serious
      threat for poultry and humans.

PMID- 29470166
TI  - What Drives Health Professionals to Tweet About #HPVvaccine? Identifying
      Strategies for Effective Communication.
AB  - INTRODUCTION: We conducted this study to quantify how health professionals use
      Twitter to communicate about the human papillomavirus (HPV) vaccine. METHODS: We
      collected 193,379 tweets from August 2014 through July 2015 that contained key
      words related to HPV vaccine. We classified all tweets on the basis of user,
      audience, sentiment, content, and vaccine characteristic to examine 3 groups of
      tweets: 1) those sent by health professionals, 2) those intended for parents, and
      3) those sent by health professionals and intended for parents. For each group,
      we identified the 7-day period in our sample with the most number of tweets
      (spikes) to report content. RESULTS: Of the 193,379 tweets, 20,451 tweets were
      from health professionals; 16,867 tweets were intended for parents; and 1,233
      tweets overlapped both groups. The content of each spike varied per group. The
      largest spike in tweets from health professionals (n = 851) focused on
      communicating recently published scientific evidence. Most tweets were positive
      and were about resources and boys. The largest spike in tweets intended for
      parents (n = 1,043) centered on a national awareness day and were about
      resources, personal experiences, boys, and girls. The largest spike in tweets
      from health professionals to parents (n = 89) was in January and centered on an
      event hosted on Twitter that focused on cervical cancer awareness month.
      CONCLUSION: Understanding drivers of tweet spikes may help shape future
      communication and outreach. As more parents use social media to obtain health
      information, health professionals and organizations can leverage awareness events
      and personalize messages to maximize potential reach and parent engagement.

PMID- 29470167
TI  - Role of Race/Ethnicity, Language, and Insurance in Use of Cervical Cancer
      Prevention Services Among Low-Income Hispanic Women, 2009-2013.
AB  - INTRODUCTION: Hispanic women in the United States have an elevated risk of
      cervical cancer, but the existing literature does not reveal why this disparity
      persists. METHODS: We performed a retrospective cohort analysis of 17,828 low
      income women aged 21 to 64 years seeking care at Oregon community health centers
      served by a hosted, linked electronic health record during 2009 through 2013. We
      assessed the odds of having had Papanicolaou (Pap) tests and receiving human
      papillomavirus (HPV) vaccine, by race/ethnicity, insurance status, and language.
      RESULTS: Hispanic women, regardless of pregnancy status or insurance, had greater
      odds of having had Pap tests than non-Hispanic white women during the study
      period. English-preferring Hispanic women had higher odds of having had Pap tests
      than Spanish-preferring Hispanic women (OR, 2.08; 95% confidence interval [CI],
      1.63-2.66) but lower odds of having received HPV vaccination (OR, 0.21; 95% CI,
      0.12-0.38). Uninsured patients, regardless of race/ethnicity, had lower odds of
      HPV vaccine initiation than insured patients did. Once a single dose was
      received, there were no significant racial/ethnic differences in vaccine series
      completion. CONCLUSION: In this sample of low-income women seeking care at Oregon
      community health centers, we found minimal racial/ethnic disparities in the
      receipt of cervical cancer prevention services. Inequities by insurance status,
      especially in the receipt of HPV vaccine, persist. Community health center-based
      care may be a useful model to address racial/ethnic disparities in prevention,
      but this model would need further population-wide study.

PMID- 29470168
TI  - Evaluation of the Healthy Lifestyles Initiative for Improving Community Capacity
      for Childhood Obesity Prevention.
AB  - PURPOSE AND OBJECTIVES: Policy, systems, and environmental approaches are
      recommended for preventing childhood obesity. The objective of our study was to
      evaluate the Healthy Lifestyles Initiative, which aimed to strengthen community
      capacity for policy, systems, and environmental approaches to healthy eating and
      active living among children and families. INTERVENTION APPROACH: The Healthy
      Lifestyles Initiative was developed through a collaborative process and
      facilitated by community organizers at a local children's hospital. The
      initiative supported 218 partners from 170 community organizations through
      training, action planning, coalition support, one-on-one support, and the
      dissemination of materials and sharing of resources. EVALUATION METHODS: Eighty
      initiative partners completed a brief online survey on implementation strategies
      engaged in, materials used, and policy, systems, and environmental activities
      implemented. In accordance with frameworks for implementation science, we
      assessed associations among the constructs by using linear regression to identify
      whether and which of the implementation strategies were associated with materials
      used and implementation of policy, systems, and environmental activities targeted
      by the initiative. RESULTS: Each implementation strategy was engaged in by 30% to
      35% of the 80 survey respondents. The most frequently used materials were
      educational handouts (76.3%) and posters (66.3%). The most frequently implemented
      activities were developing or continuing partnerships (57.5%) and reviewing
      organizational wellness policies (46.3%). Completing an action plan and the
      number of implementation strategies engaged in were positively associated with
      implementation of targeted activities (action plan, effect size = 0.82; number of
      strategies, effect size = 0.51) and materials use (action plan, effect size =
      0.59; number of strategies, effect size = 0.52). Materials use was positively
      associated with implementation of targeted activities (effect size = 0.35).
      IMPLICATIONS FOR PUBLIC HEALTH: Community-capacity-building efforts can be
      effective in supporting community organizations to engage in policy, systems, and
      environmental activities for healthy eating and active living. Multiple
      implementation strategies are likely needed, particularly strategies that involve
      a high level of engagement, such as training community organizations and working
      with them on structured action plans.

PMID- 29470169
TI  - Multi-Attributed Graph Matching With Multi-Layer Graph Structure and Multi-Layer
      Random Walks.
AB  - This paper addresses the multi-attributed graph matching problem, which considers
      multiple attributes jointly while preserving the characteristics of each
      attribute for graph matching. Since most of conventional graph matching
      algorithms integrate multiple attributes to construct a single unified attribute
      in an oversimplified manner, the information from multiple attributes is often
      not completely utilized. In order to solve this problem, we propose a novel multi
      layer graph structure that can preserve the characteristics of each attribute in
      separated layers, and also propose a multi-attributed graph matching algorithm
      based on random walk centrality with the proposed multi-layer graph structure. We
      compare the proposed algorithm with other state-of-the-art graph matching
      algorithms based on a single-layer structure using synthetic and real data sets
      and demonstrate the superior performance of the proposed multi-layer graph
      structure and the multi-attributed graph matching algorithm.

PMID- 29470171
TI  - Hyperspectral Image Classification With Markov Random Fields and a Convolutional
      Neural Network.
AB  - This paper presents a new supervised classification algorithm for remotely sensed
      hyperspectral image (HSI) which integrates spectral and spatial information in a
      unified Bayesian framework. First, we formulate the HSI classification problem
      from a Bayesian perspective. Then, we adopt a convolutional neural network (CNN)
      to learn the posterior class distributions using a patch-wise training strategy
      to better use the spatial information. Next, spatial information is further
      considered by placing a spatial smoothness prior on the labels. Finally, we
      iteratively update the CNN parameters using stochastic gradient decent and update
      the class labels of all pixel vectors using -expansion min-cut-based algorithm.
      Compared with the other state-of-the-art methods, the classification method
      achieves better performance on one synthetic data set and two benchmark HSI data
      sets in a number of experimental settings.

PMID- 29470170
TI  - Sub-Network Kernels for Measuring Similarity of Brain Connectivity Networks in
      Disease Diagnosis.
AB  - As a simple representation of interactions among distributed brain regions, brain
      networks have been widely applied to automated diagnosis of brain diseases, such
      as Alzheimer's disease (AD) and its early stage, i.e., mild cognitive impairment
      (MCI). In brain network analysis, a challenging task is how to measure the
      similarity between a pair of networks. Although many graph kernels (i.e., kernels
      defined on graphs) have been proposed for measuring the topological similarity of
      a pair of brain networks, most of them are defined using general graphs, thus
      ignoring the uniqueness of each node in brain networks. That is, each node in a
      brain network denotes a particular brain region, which is a specific
      characteristics of brain networks. Accordingly, in this paper, we construct a
      novel sub-network kernel for measuring the similarity between a pair of brain
      networks and then apply it to brain disease classification. Different from
      current graph kernels, our proposed sub-network kernel not only takes into
      account the inherent characteristic of brain networks, but also captures multi
      level (from local to global) topological properties of nodes in brain networks,
      which are essential for defining the similarity measure of brain networks. To
      validate the efficacy of our method, we perform extensive experiments on subjects
      with baseline functional magnetic resonance imaging data obtained from the
      Alzheimer's disease neuroimaging initiative database. Experimental results
      demonstrate that the proposed method outperforms several state-of-the-art graph
      based methods in MCI classification.

PMID- 29470172
TI  - Hookworm Detection in Wireless Capsule Endoscopy Images With Deep Learning.
AB  - As one of the most common human helminths, hookworm is a leading cause of
      maternal and child morbidity, which seriously threatens human health. Recently,
      wireless capsule endoscopy (WCE) has been applied to automatic hookworm
      detection. Unfortunately, it remains a challenging task. In recent years, deep
      convolutional neural network (CNN) has demonstrated impressive performance in
      various image and video analysis tasks. In this paper, a novel deep hookworm
      detection framework is proposed for WCE images, which simultaneously models
      visual appearances and tubular patterns of hookworms. This is the first deep
      learning framework specifically designed for hookworm detection in WCE images.
      Two CNN networks, namely edge extraction network and hookworm classification
      network, are seamlessly integrated in the proposed framework, which avoid the
      edge feature caching and speed up the classification. Two edge pooling layers are
      introduced to integrate the tubular regions induced from edge extraction network
      and the feature maps from hookworm classification network, leading to enhanced
      feature maps emphasizing the tubular regions. Experiments have been conducted on
      one of the largest WCE datasets with WCE images, which demonstrate the
      effectiveness of the proposed hookworm detection framework. It significantly
      outperforms the state-of-the-art approaches. The high sensitivity and accuracy of
      the proposed method in detecting hookworms shows its potential for clinical
      application.

PMID- 29470173
TI  - Preemptive NUDT15 genotyping: redefining the management of patients with
      thiopurine-induced toxicity.
AB  - BACKGROUND: Thiopurine methyltransferase (TPMT) gene variants have achieved
      limited success in predicting the outcome of thiopurine therapy, which shows wide
      inter-individual variations. The literature indicates a strong association
      between the NUDT15 gene variant and thiopurine-induced toxicity in Asian
      patients. The present study intends to explore the role of the NUDT15 variant
      (C415T) in Indian patients on thiopurine therapy. METHODS: NUDT15 and TPMT
      genotyping were performed using amplification-refractory mutation system
      polymerase chain reaction (ARMS-PCR) and the restriction fragment length
      polymorphism (RFLP) technique. RESULTS: Of 370 samples received for TPMT testing,
      206 samples were available for NUDT15 genotyping. The NUDT15 risk allele
      frequency was 10.7%, with the frequency of wild, heterozygous and mutant
      genotypes being 80.6%, 17.5% and 1.9%, respectively. TPMT variants were seen in
      13 of 370 (3.5%) patients, whereas the NUDT15 variant was seen in 40 of 206
      (19.4%) patients. Thiopurine-induced toxicity information was available for 101
      patients, among whom 10 developed leukopenia and all harbored the NUDT15 variant
      (p<0.0001). NUDT15 was clinically more relevant than TPMT in terms of sensitivity
      and specificity, as well as with a statistically significant difference in
      thiopurine dose requirement for patients with the NUDT15 variant. CONCLUSIONS: A
      preemptive NUDT15 genotyping approach can therefore help identify high-risk
      patients (NUDT15 C415T positive) who could benefit from thiopurine dose
      reduction, thereby preventing fatal thiopurine-induced toxicity.

PMID- 29470174
TI  - Antidiabetic and protective effects of the aqueous extract of Arbutus unedo L. in
      streptozotocin-nicotinamide-induced diabetic mice.

PMID- 29470175
TI  - Modified HuffBit Compress Algorithm - An Application of R.
AB  - The databases of genomic sequences are growing at an explicative rate because of
      the increasing growth of living organisms. Compressing deoxyribonucleic acid
      (DNA) sequences is a momentous task as the databases are getting closest to its
      threshold. Various compression algorithms are developed for DNA sequence
      compression. An efficient DNA compression algorithm that works on both repetitive
      and non-repetitive sequences known as "HuffBit Compress" is based on the concept
      of Extended Binary Tree. In this paper, here is proposed and developed a modified
      version of "HuffBit Compress" algorithm to compress and decompress DNA sequences
      using the R language which will always give the Best Case of the compression
      ratio but it uses extra 6 bits to compress than best case of "HuffBit Compress"
      algorithm and can be named as the "Modified HuffBit Compress Algorithm". The
      algorithm makes an extended binary tree based on the Huffman Codes and the
      maximum occurring bases (A, C, G, T). Experimenting with 6 sequences the proposed
      algorithm gives approximately 16.18 % improvement in compression ration over the
      "HuffBit Compress" algorithm and 11.12 % improvement in compression ration over
      the "2-Bits Encoding Method".

PMID- 29470176
TI  - Association of insulin-like growth factor-1 and IGF binding protein-3 with 25
      hydroxy vitamin D in pre-pubertal and adolescent Indian girls.
AB  - BACKGROUND: There is a high prevalence of vitamin D deficiency (VDD) in India.
      Molecular mechanisms suggest a strong relationship between vitamin D and growth
      factors. However, there is a paucity of literature with regard to a relationship
      between insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding
      protein-3 (IGFBP-3) and vitamin D particularly in subjects with VDD. The
      objective of the study was to assess the relationship between growth factors and
      serum vitamin D-parathormone (PTH) status in school girls and study the impact of
      vitamin D supplementation on growth factors in pre-pubertal girls with VDD.
      METHODS: Our study subjects were apparently healthy school girls aged 6-18 years.
      The baseline height, weight, body mass index (BMI), pubertal status, serum 25
      hydroxy vitamin D (25OHD), PTH, IGF-1 and IGFBP-3 were assessed in 847 girls aged
      6-18 years and in 190 pre-pubertal girls with VDD following supplementation.
      RESULTS: The mean age, BMI and serum 25OHD of girls were 11.5+/-3.2 years, 18.7+/
      4.8 kg/m2 and 9.9+/-5.6 ng/mL, respectively. VDD was observed in 94.6% of girls.
      Unadjusted serum IGF-1 levels and IGF-1/IGFBP-3 molar ratio were significantly
      higher in girls with severe VDD as compared to girls with mild-to-moderate VDD.
      However, these differences disappeared when adjusted for age, height or sexual
      maturation. The serum IGF-1 and IGFBP-3 levels increased significantly post
      supplementation with vitamin D. CONCLUSIONS: There were no differences in serum
      IGF-1 levels and the IGF-1/IGFBP-3 molar ratio among VDD categories when adjusted
      for age, height and sexual maturation in girls. Vitamin D supplementation
      resulted in a significant increase in serum IGF-1 levels in VDD pre-pubertal
      girls.

PMID- 29470177
TI  - Investigating the changes in amino acid values in premature infants: a pilot
      study.
AB  - BACKGROUND: The objective of the study was to investigate the changes in amino
      acid (AAs) values in premature infants. METHODS: A total of 2159 premature and/or
      low birth weight infants were recruited for this study. They were divided into
      three groups: premature infants with normal birth weight (G1), simple low birth
      weight infants (G2) and premature combined with low birth weight infants (G3).
      The tandem mass spectrometry technique was used to detect the levels of 11 AAs in
      neonatal blood. RESULTS: Compared with normal babies, there were eight and five
      AAs that significantly changed in G1 and G2, respectively. It was worth noting
      that the changes greatly exacerbated when the babies were both premature and of
      low birth weight. All the levels of AAs demonstrated significant changes in G3
      compared with the normal control group (G4). With the increase in gestational
      age, the AAs in premature infants tended to the levels in normal newborns.
      Meanwhile, there was a correlation between AAs and birth weight. Four AAs
      significantly changed with the increase in body weight. Among normal newborns,
      the levels of AAs in girls were significantly higher than in boys. However, if
      the newborns were premature or had low birth weight, the differences between AA
      values and sexual distinction would decrease. In the end, we established the
      specific reference ranges of AAs for premature and/or low birth weight infants.
      CONCLUSIONS: There were significant differences in AAs in the premature and/or
      low birth weight infants. Gestational age and birth weight were two important
      factors inflecting the AAs metabolism.

PMID- 29470178
TI  - Erroneous conclusion due to mis-calculation of data: reply to Rai SE, Sidhu AK,
      Krishnan RJ. Transfusion-associated necrotizing enterocolitis re-evaluated: a
      systematic review and meta-analysis. J Perinat Med 2017.

PMID- 29470179
TI  - Health care curricula in multicultural societies.

PMID- 29470180
TI  - Opioid Abuse or Dependence Increases 30-day Readmission Rates after Major
      Operating Room Procedures: A National Readmissions Database Study.
AB  - BACKGROUND: Although opioids remain the standard therapy for the treatment of
      postoperative pain, the prevalence of opioid misuse is rising. The extent to
      which opioid abuse or dependence affects readmission rates and healthcare
      utilization is not fully understood. It was hypothesized that surgical patients
      with a history of opioid abuse or dependence would have higher readmission rates
      and healthcare utilization. METHODS: A retrospective cohort analysis was
      performed of patients undergoing major operating room procedures in 2013 and 2014
      using the National Readmission Database. Patients with opioid abuse or dependence
      were identified using International Classification of Diseases codes. The primary
      outcome was 30-day hospital readmission rate. Secondary outcomes included
      hospital length of stay and estimated hospital costs. RESULTS: Among the
      16,016,842 patients who had a major operating room procedure whose death status
      was known, 94,903 (0.6%) had diagnoses of opioid abuse or dependence. After
      adjustment for potential confounders, patients with opioid abuse or dependence
      had higher 30-day readmission rates (11.1% vs. 9.1%; odds ratio 1.26; 95% CI,
      1.22 to 1.30), longer mean hospital length of stay at initial admission (6 vs. 4
      days; P < 0.0001), and higher estimated hospital costs during initial admission
      ($18,528 vs. $16,617; P < 0.0001). Length of stay was also higher at readmission
      (6 days vs. 5 days; P < 0.0001). Readmissions for infection (27.0% vs. 18.9%; P <
      0.0001), opioid overdose (1.0% vs. 0.1%; P < 0.0001), and acute pain (1.0% vs.
      0.5%; P < 0.0001) were more common in patients with opioid abuse or dependence.
      CONCLUSIONS: Opioid abuse and dependence are associated with increased
      readmission rates and healthcare utilization after surgery. VISUAL ABSTRACT: An
      online visual overview is available for this article at
      http://links.lww.com/ALN/B704.

PMID- 29470181
TI  - Prevention and Management of Thromboembolism in Pregnancy When Heparins Are Not
      an Option.
AB  - Heparins, unfractionated heparin, and low molecular weight heparin, are the
      preferred anticoagulants in pregnancy. There are circumstances, however, in which
      an alternative to heparin should be considered. These circumstances include, the
      presence of heparin resistance, a heparin allergy manifesting as heparin-induced
      skin reactions or heparin-induced thrombocytopenia, and the presence of a
      mechanical heart valve. From time to time, the obstetrician is called on to make
      recommendations about anticoagulants in pregnancy, including in circumstances in
      which an alternative to heparin has been suggested or is necessary. In this
      article, these circumstances are reviewed and alternative anticoagulants are
      discussed.

PMID- 29470182
TI  - Diagnosis and Management of VTE in Pregnancy.
AB  - Venous thromboembolism is a leading cause of maternal death. Because of the low
      absolute frequency of events, however, outcome-based clinical data are limited.
      Consequently, clinicians must additionally rely both on published guidelines and
      on extrapolation of data from studies focused on nonpregnant individuals. The
      diagnosis and treatment of deep vein thrombosis, pulmonary embolism, and cerebral
      vein and dural sinus thrombosis are complicated by pregnancy, and often require
      modifications to standard diagnostic and treatment algorithms outside of
      pregnancy. Treatment of VTE in pregnant women is in particular need of future
      research.

PMID- 29470183
TI  - The Central Effects of Androgenic-anabolic Steroid Use.
AB  - : Millions of men use androgenic-anabolic steroids (AAS) to stimulate muscle
      growth and improve physical appearance. Although 1 out of 3 people who uses
      androgenic-anabolic steroids develops a steroid use disorder, the effects of the
      drugs on the central nervous system and the psyche are still not well understood.
      Although most addictive substances improve mood immediately after administration,
      AAS exert less pronounced euphoric effects. Instead, they are primarily taken for
      the delayed gratification of increased muscle mass. Withdrawal from AAS may lead
      to a range of somatic and psychiatric symptoms, and, in many cases, comprehensive
      treatment supervised by an endocrinologist and a psychiatrist is required.

PMID- 29470184
TI  - Impact of 3D virtual planning on reconstruction of mandibular and maxillary
      surgical defects in head and neck oncology.
AB  - PURPOSE OF REVIEW: This review describes the advances in 3D virtual planning for
      mandibular and maxillary reconstruction surgical defects with full prosthetic
      rehabilitation. The primary purpose is to provide an overview of various
      techniques that apply 3D technology safely in primary and secondary
      reconstructive cases of patients suffering from head and neck cancer. RECENT
      FINDINGS: Methods have been developed to overcome the problem of control over the
      margin during surgery while the crucial decision with regard to resection margin
      and planning of osteotomies were predetermined by virtual planning. The unlimited
      possibilities of designing patient-specific implants can result in creative
      uniquely applied solutions for single cases but should be applied wisely with
      knowledge of biomechanical engineering principles. SUMMARY: The high surgical
      accuracy of an executed 3D virtual plan provides tumor margin control during
      ablative surgery and the possibility of planned combined use of osseus free flaps
      and dental implants in the reconstruction in one surgical procedure. A thorough
      understanding of the effects of radiotherapy on the reconstruction, soft tissue
      management, and prosthetic rehabilitation is imperative in individual cases when
      deciding to use dental implants in patients who received radiotherapy.

PMID- 29470185
TI  - Psychological Factors and the Development of Chronic Whiplash-associated
      Disorder(s): A Systematic Review.
AB  - OBJECTIVES: To assess which psychological factors are important in the
      development of chronic whiplash symptoms. METHODS: Searches were conducted across
      PubMed, CINAHL, Scopus, and PsychINFO up until March 2017. Studies were included
      if they investigated psychological prognostic factors in association with
      recovery from a whiplash injury. Studies also had to be prospective, cohort,
      follow-up or observational studies, have a 6 month follow-up and published in
      English. Quality assessments were conducted by 2 independent reviewers. Thirty
      one articles were included investigating 34 psychological factors. RESULTS: Poor
      expectations of recovery, posttraumatic stress symptoms and passive coping
      emerged as the most consistent prognostic factors of chronic neck pain and/or
      disability after a whiplash injury. Anxiety, travel anxiety, depression,
      personality, precollision distress, general psychological distress, and avoidance
      behavior were not associated with chronic whiplash problems.

PMID- 29470186
TI  - A Comparison of Outcomes Between Open Hysterectomy and Robotic-Assisted
      Hysterectomy for Endometrial Cancer Using the National Cancer Database.
AB  - PURPOSE: The purpose of this study is to evaluate usage patterns and outcomes of
      women who underwent open hysterectomy (OH) versus robotic assisted-hysterectomy
      (RAH) for the treatment of endometrial cancer. METHODS: Women with nonmetastatic
      endometrial adenocarcinoma diagnosed between 2010 and 2012, who either underwent
      an OH or RAH, were selected from the National Cancer Database. The chi, Fisher
      exact, or Mann-Whitney U tests were used where appropriate to compare outcomes
      between groups. Multivariable logistic regression was used to analyze for
      predictors for RAH and other outcome variables. RESULTS: A total of 43,985 women
      were included in this study with a median age of 61 years. Of these, 23,872
      (54.3%) underwent RAH and 20,113 (45.7%) underwent OH. The usage of RAH increased
      from 43.0% in 2010 to 63.8% in 2012 (P < 0.001). Women receiving RAH were more
      commonly found to have a Charlson comorbidity score of 0 to 1, lower pathologic
      stage, nonblack race, treatment at a comprehensive center, and had insurance
      other than Medicaid. Robotic-assisted hysterectomy was associated with a shorter
      inpatient stay, lower readmission rates, and lower 30- and 90-day mortality rates
      (P < 0.001 for all comparisons). There was a significant improvement in overall
      survival favoring RAH, 96.1% versus 94.0%, which persisted on multivariable
      logistic regression (P < 0.001). CONCLUSIONS: In this large, hospital-based
      analysis, RAH was associated with decreased length of stay, lower readmission
      rates, and less perioperative mortality. However, socioeconomic status continues
      to remain a barrier to equal treatment allocation. Overall survival was improved
      with RAH, but the follow-up is limited, and this finding must be interpreted with
      caution.

PMID- 29470187
TI  - The Danish Gynecological Cancer Nursing Database: Creating Evidence for Quality
      Improvements in Preoperative and Postoperative Cancer Care.
AB  - OBJECTIVE: Quality of preoperative and postoperative care is crucial to improve
      postoperative outcome of cancer surgery and to ensure that neither complications
      nor a poor general condition delays any subsequent radiochemotherapy or recovery.
      On this background, the Danish Gynecological Cancer Database (DGCD) established a
      nursing database in 2011. The aim of DGCD Nursing is to monitor the quality of
      preoperative and postoperative care and to generate data for research. MATERIAL
      AND METHODS: In accordance with the current data protection legislation, real
      time data are entered by clinical nurses at all national cancer centers. The DGCD
      Nursing includes data of preoperative and postoperative care, and nurses are
      independently represented in the steering committee. The aim of the present
      article is to present the first results from DGCD Nursing and the national care
      improvements that have followed. RESULTS: With national coverage of an average of
      94%, 5726 patients have been registered since 2011. In patients undergoing
      surgery for ovarian, endometrial, and cervical cancer, 436 different variables
      monitor central preoperative and postoperative care elements within mobilization,
      nutritional status, pain score, vital functions, and psychosocial support.
      CONCLUSIONS: At national level, DGCD offers a comprehensive overview of the total
      patient pathway within gynecological cancer surgery. The DGCD Nursing has added
      to the quality and implementation of evidence-based preoperative and
      postoperative care and in addition supported formation of professional networks.
      With a continued validation of data, DGCD Nursing now constitutes a sound and
      unique basis for research within the field of preoperative and postoperative
      cancer care.

PMID- 29470188
TI  - Extrapelvic Sentinel Lymph Nodes in Endometrial Cancer Patients With Unmapped
      Pelvic Side: A Brief Report.
AB  - OBJECTIVE: The aim of the study was to evaluate extrapelvic sentinel lymph nodes
      (SLNs) in clinical early-stage endometrial cancer patients with unmapped pelvic
      side(s) during fluorescent imaging-based sentinel mapping. MATERIALS AND METHODS:
      Eligible patients underwent sentinel mapping using cervical injection of
      indocyanine green and near-infrared florescent imaging compatible endoscopic
      systems. Pelvic SLNs were identified and resected. If bilateral mapping was not
      achieved, upper lymph nodes areas including presacral, upper common iliac, and
      para-aortic caval regions were explored for any SLN. Systematic lymphadenectomy
      was performed after applying SLN algorithm steps. RESULTS: In 24 of 101 patients,
      bilateral pelvic mapping was not achieved. Bilateral unmapping was seen in 4 of
      24 and unilateral pelvic side mapping in 20 of 24 patients. There was no
      extrapelvic SLN among 4 cases with bilateral pelvic unmapping, whereas 8 (40%) of
      20 patients with unilateral pelvic mapping had extrapelvic SLNs. Five of
      extrapelvic SLNs were in presacral, 2 in upper common iliac, and 1 in paracaval
      regions. CONCLUSIONS: Observing for extrapelvic SLNs in cases with unmapped
      pelvic side(s) could increase detection rate of SLN mapping in clinical early
      stage endometrial cancer.

PMID- 29470189
TI  - Letter From the Editor, March 2018.

PMID- 29470190
TI  - Blood transfusion management in the severely bleeding military patient.
AB  - PURPOSE OF REVIEW: Hemorrhage remains the primary cause of preventable death on
      the battlefield and in civilian trauma. Hemorrhage control is multifactorial and
      starts with point-of-injury care. Surgical hemorrhage control and time from
      injury to surgery is paramount; however, interventions in the prehospital
      environment and perioperative period affect outcomes. The purpose of this review
      is to understand concepts and strategies for successful management of the
      bleeding military patient. Understanding the life-threatening nature of
      coagulopathy of trauma and implementing strategies aimed at full spectrum
      hemorrhage management from point of injury to postoperative care will result in
      improved outcomes in patients with life-threatening bleeding. RECENT FINDINGS:
      Timely and appropriate therapies impact survival. Blood product resuscitation for
      life-threatening hemorrhage should either be with whole blood or a component
      therapy strategy that recapitulates the functionality of whole blood. The US
      military has transfused over 10 000 units of whole blood since the beginning of
      the wars in Iraq and Afghanistan. The well recognized therapeutic benefits of
      whole blood have pushed this therapy far forward into prehospital care in both US
      and international military forces. Multiple hemostatic adjuncts are available
      that are likely beneficial to the bleeding military patient; and other products
      and techniques are under active investigation. SUMMARY: Lessons learned in the
      treatment of combat casualties will likely continue to have positive impact and
      influence and the management of hemorrhage in the civilian trauma setting.

PMID- 29470192
TI  - Sensitivity of a Reduced EEG Montage for Seizure Detection in the Neurocritical
      Care Setting.
AB  - INTRODUCTION: Neurocritical care units commonly implement the double-distance
      reduced EEG montage in postoperative neurosurgic patients who have structural
      barriers that hinder the placement of a standard 10-20 system array. Despite its
      widespread use, its sensitivity has not been adequately addressed. We evaluated
      the sensitivity and specificity of this montage for seizure detection. METHODS:
      One hundred fifty-five full-montage continuous EEGs (cEEGs) completed in the
      Johns Hopkins University neurocritical care unit containing unequivocal
      electrographic seizures, status epilepticus, or other abnormalities were
      selected, comprising 73 ictal and 82 nonictal EEGs. EEGs were reformatted to the
      reduced montage, and 2-hour clips were reviewed independently by 2
      epileptologists who documented the presence of seizures, status, or background
      abnormalities. RESULTS: The sensitivity and specificity of the reduced montage
      for electrographic seizure detection was 81% and 92% with substantial interrater
      agreement (kappa 0.71). The sensitivity for status epilepticus was lower at 69%,
      but specificity remained high at 97% (kappa 0.67). Several EEGs miscategorized as
      nonictal were labeled as rather having rhythmic activity or periodic discharges.
      Evaluation of background patterns on the ictal-interictal continuum resulted in
      sensitivities ranging from 68% to 83%. CONCLUSIONS: Although the specificity of
      the reduced array is good, epileptologists should remain vigilant when monitoring
      patients using this montage, given its reduced sensitivity for epileptic
      activity, especially status epilepticus.

PMID- 29470191
TI  - Characterization of Postinfusion Phenotypic Differences in Fresh Versus
      Cryopreserved TCR Engineered Adoptive Cell Therapy Products.
AB  - Adoptive cell therapy (ACT) consisting of genetically engineered T cells
      expressing tumor antigen-specific T-cell receptors displays robust initial
      antitumor activity, followed by loss of T-cell activity/persistence and frequent
      disease relapse. We characterized baseline and longitudinal T-cell phenotype
      variations resulting from different manufacturing and administration protocols in
      patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1
      clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors
      transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination.
      Patients were divided into cohorts based on several manufacturing changes in the
      generation and administration of the transgenic T cells: decreasing ex vivo
      stimulation/expansion time, increased cell dose, and receiving fresh instead of
      cryopreserved cells. T-cell phenotypes were analyzed by flow cytometry at
      baseline and longitudinally in peripheral blood. Transgenic T cells with shorter
      ex vivo culture/expansion periods displayed significantly increased expression of
      markers associated with less differentiated naive/memory populations, as well as
      significantly decreased expression of the inhibitory receptor programmed death 1
      (PD1). Patients receiving fresh infusions of transgenic cells demonstrated
      expansion of central memory T cells and delayed acquisition of PD1 expression
      compared with patients who received cryopreserved products. Freshly infused
      transgenic T cells showed persistence and expansion of naive and memory T-cell
      populations and delayed acquisition of PD1 expression, which correlated with this
      cohort's superior persistence of transgenic cells and response to dendritic cell
      vaccines. These results may be useful in designing future ACT protocols.

PMID- 29470193
TI  - Breakthrough Reactions to Gadobenate Dimeglumine.
AB  - PURPOSE: The aim of this study was to determine the severity of breakthrough
      reactions to gadobenate dimeglumine in patients premedicated with a 13-hour
      premedication regimen. METHODS: Institutional review board approval was obtained
      and informed consent waived for this Health Insurance Portability and
      Accountability Act-compliant retrospective cohort study. All acute allergic-like
      reactions to gadobenate dimeglumine from 11/1/2008 to 1/31/2016 were identified.
      Of these, 19 allergic-like reactions followed 13-hour premedication: 150 mg
      prednisone and 50 mg diphenhydramine (ie, "breakthrough reactions"). Reasons for
      premedication, risk factors, index reaction characteristics, and breakthrough
      reaction characteristics were catalogued. Reaction severities were assigned using
      American College of Radiology guidelines. Severities of breakthrough (n = 19) and
      nonbreakthrough reactions (n = 97) were compared with the Cochran-Armitage test
      for trend. RESULTS: Premedication was most commonly given (63% [12/19]) for a
      previous allergic-like reaction to gadolinium-based contrast material (GBCM); in
      37% (7/19), it was given for a different risk factor. In those premedicated for a
      previous allergic-like reaction to GBCM of known severity (n = 9), the
      breakthrough reaction severity was the same as index reaction severity in 56%
      (5/9), less severe in 11% (1/9), and of greater severity in 33% (3/9). Two severe
      breakthrough reactions occurred; both were in subjects premedicated for risk
      factors other than a previous GBCM reaction. No subjects died. Five subjects were
      reexposed to GBCM a total of 9 times; no repeat breakthrough reactions occurred.
      Breakthrough reactions were more severe than nonbreakthrough reactions (P =
      0.046), but the level of significance was borderline. CONCLUSION: Premedication
      does not eliminate severe reactions to gadobenate dimeglumine. Breakthrough
      reactions to gadobenate dimeglumine can be of greater severity than index
      reactions.

PMID- 29470194
TI  - Magnetization Transfer Ratio in Peripheral Nerve Tissue: Does It Depend on Age or
      Location?
AB  - BACKGROUND AND PURPOSE: Magnetization transfer contrast imaging provides indirect
      information on the concentration of "bound" water protons and their interactions
      with "free" water molecules. The purpose of this study is to analyze location-
      and age-dependent changes in the magnetization transfer ratio (MTR) of lower
      extremity nerves. MATERIALS AND METHODS: Ten younger (20-32 years) and 5 older
      (50-63 years) healthy volunteers underwent magnetization transfer contrast
      imaging at 3 Tesla Two 3-dimensional gradient echo sequences with and without an
      off-resonance saturation pulse (repetition time: 58 milliseconds; echo time: 2.46
      milliseconds; band width: 530 Hz/Px; flip angle: alpha = 7 degrees ) were
      acquired at 3 different locations covering the proximal thigh to the distal lower
      leg in the group of younger volunteers and at 2 different locations covering the
      proximal to distal thigh in the group of older volunteers. Sciatic and tibial
      nerve regions of interest (ROIs) were manually drawn and additional ROIs were
      placed in predetermined muscles. Magnetization transfer ratios were extracted
      from respective ROIs and calculated for each individual and location. RESULTS: In
      young volunteers, mean values of nerve and muscle MTR were not different between
      the proximal thigh (nerve: 20.34 +/- 0.91; muscle: 31.71 +/- 0.29), distal thigh
      (nerve: 19.90 +/- 0.98; P = 0.76; muscle: 31.53 +/- 0.69; P = 0.87), and lower
      leg (nerve: 20.82 +/- 1.07; P = 0.73; muscle: 32.44 +/- 1.11; P = 0.51). An age
      dependent decrease of sciatic nerve MTR was observed in the group of older
      volunteers (16.95 +/- 1.2) compared with the group of younger volunteers (20.12
      +/- 0.65; P = 0.019). Differences in muscle MTR were not significant between
      older (31.01 +/- 0.49) and younger (31.62 +/- 0.37; P = 0.20) volunteers.
      CONCLUSION: The MTR of lower extremity nerves shows no proximal-to-distal
      gradient in young healthy volunteers but decreases with age. For future studies
      using MTR in peripheral nerve disorders, these findings suggest that referencing
      magnetization transfer contrast values in terms of age, but not anatomical nerve
      location is required.

PMID- 29470195
TI  - Saving the Safety Net.
AB  - Will Medicaid 'reform' render it useless?

PMID- 29470196
TI  - Nursing and Politics.

PMID- 29470197
TI  - Nursing and Politics.

PMID- 29470198
TI  - Nursing and Politics.

PMID- 29470199
TI  - Ethical Issues.

PMID- 29470200
TI  - Addressing HIV Stigma in Health Care.
AB  - Strategies to address this potent barrier to treatment and prevention.

PMID- 29470201
TI  - AMA Resolution Opposes Independent Practice by APRNs.
AB  - An old debate heats up again.

PMID- 29470202
TI  - ED Visits for Self-Harm by Girls Are on the Rise.
AB  - A nearly 20% increase since 2008 worries experts, as the behavior is a suicide
      risk factor.

PMID- 29470204
TI  - Seniors Need Hip Fracture Surgery Within 24 Hours.
AB  - Early surgery found to reduce life-threatening complications.

PMID- 29470205
TI  - Addressing the ICU Patient's Information Needs.
AB  - Nurse researchers create an educational pathway.

PMID- 29470206
TI  - CMS Delays Fines for Nursing Home Infractions.
AB  - Moratorium elicits concern among nursing home advocates.

PMID- 29470208
TI  - The CDC's HI-5 Initiative.
AB  - A plan to improve community health in five years.

PMID- 29470211
TI  - FDA Warns Against Unregulated Products.

PMID- 29470212
TI  - Risk of Heart-Related Death From Gout Medication.

PMID- 29470216
TI  - Creamed Dishes for the Convalescent.
AB  - Editor's note: From its first issue in 1900 through to the present day, AJN has
      unparalleled archives detailing nurses' work and lives over more than a century.
      These articles not only chronicle nursing's growth as a profession within the
      context of the events of the day, but also reveal prevailing societal attitudes
      about women, health care, and human rights. Today's nursing school curricula
      rarely include nursing's history, but it's a history worth knowing. To this end,
      From the AJN Archives highlights articles selected to fit today's topics and
      times.This excerpt, from an article in the June 1915 issue, illustrates the ways
      in which nurses of that era were intimately involved in feeding their patients.
      Cora McCabe Sargent, a nurse who wrote several nutrition-related articles for
      AJN, writes that "while it is not at all essential that a good cook understand
      nursing the sick, it is most important that a good nurse have a certain,
      practical knowledge of cooking." Here she extols the value of a meticulously made
      cream sauce in tempting "the capricious appetite of the sick." (To read the full
      article, go to http://links.lww.com/AJN/A108.)Today's nurses are still concerned
      with patient nutrition, often addressing the nutritional needs of a community or
      a particular patient population in addition to those of individual patients. For
      tools and interventions that can help nurses to support good nutrition later in
      life, see "Malnutrition in Older Adults" in this month's issue.

PMID- 29470217
TI  - The Ethical and Legal Implications of a Nurse's Arrest in Utah.
AB  - Editor's note: On July 26, 2017, Alex Wubbels, the charge nurse on the burn unit
      at the University of Utah Hospital in Salt Lake City, was arrested for refusing
      to allow a police officer to draw blood from an unconscious patient in her care.
      Her arrest, during which she was forcefully placed in handcuffs and dragged out
      of the hospital, was documented on body camera video and drew national attention.
      We asked our ethical and legal contributing editors to provide some insight on
      the issues of this case.

PMID- 29470218
TI  - Expanding RN Scope of Practice to Include Lumbar Puncture.
AB  - : The competing demands of caring for high-acuity patients, reducing health care
      costs, and improving access to specialty care are complex challenges facing all
      health care providers. One approach-empowering nurses to expand their scope of
      practice-has been successfully employed for two decades by the nurse and
      physician leadership of a neurology department in an urban academic medical
      center. This article discusses the department's implementation of a quality
      improvement initiative to enhance access to neurology services in an ambulatory
      clinic by extending nursing practice to include lumbar puncture. Outcomes data
      from 2005 to 2016 demonstrate that through the department's comprehensive
      instructional program, RNs have competently and safely acquired new skills that
      have led to an expansion of their traditional roles, improved patient access to
      specialty care, and reduced costs.

PMID- 29470219
TI  - Great Conversations: A Nurse Tackles the Puberty Talk.
AB  - For three decades, Julie Metzger has fostered dialogue between preteens and
      parents.

PMID- 29470220
TI  - Teaching Wound Care to Family Caregivers.
AB  - : This article is part of a series, Supporting Family Caregivers: No Longer Home
      Alone, published in collaboration with the AARP Public Policy Institute. Results
      of focus groups, conducted as part of the AARP Public Policy Institute's No
      Longer Home Alone video project, supported evidence that family caregivers aren't
      given the information they need to manage the complex care regimens of family
      members. This series of articles and accompanying videos aims to help nurses
      provide caregivers with the tools they need to manage their family member's
      health care at home.The articles in this new installment of the series provide
      simple and useful instructions that nurses should reinforce with family
      caregivers who perform wound care tasks. Each article also includes an
      informational tear sheet-Information for Family Caregivers-that contains links to
      instructional videos. To use this series, nurses should read the article first,
      so they understand how best to help family caregivers, and then encourage
      caregivers to watch the videos and ask questions. For additional information, see
      Resources for Nurses.

PMID- 29470221
TI  - Continuous vs. Interrupted Chest Compressions for Cardiac Arrest.
AB  - Editor's note: This is a summary of a nursing care-related systematic review from
      the Cochrane Library. For more information, see http://nursingcare.cochrane.org.

PMID- 29470222
TI  - Hormonal Contraceptives Increase Breast Cancer Risk.
AB  - According to this study.

PMID- 29470223
TI  - Meta-Analysis Shows Coffee Consumption is Generally Safe.
AB  - According to this study.

PMID- 29470224
TI  - Interprofessional Collaborative Practice Model Improves Staff Communication,
      Patient Care.
AB  - According to this study.

PMID- 29470225
TI  - No Clinical Benefit From Surgery for Shoulder Pain.
AB  - According to this study.

PMID- 29470226
TI  - Death with Dignity (and Love).
AB  - A nurse takes on a challenging new role at her ailing father's request.

PMID- 29470227
TI  - Hospitalized Patients With and Without Hemodialysis Have Markedly Different
      Vancomycin Pharmacokinetics: A Population Pharmacokinetic Model-Based Analysis.
AB  - BACKGROUND: Despite being in clinical use for about 6 decades, vancomycin dosing
      remains perplexing and complex. METHODS: A population pharmacokinetic modeling
      and simulation approach was used to evaluate the efficiency of the current
      nomogram-based dosing of vancomycin. Serum vancomycin concentrations were
      obtained as a part of routine therapeutic drug monitoring from two 500-bed
      academic medical centers. A population pharmacokinetic model was first built
      using these therapeutic drug monitoring data. Population pharmacokinetic modeling
      was conducted using NONMEM (7.2 and 7.3). The forward addition-backward
      elimination approach was used to test the covariate effects. Appropriate
      numerical and visual criteria were used as model diagnostics for checking model
      appropriateness and model qualification. The current nomogram efficiency was
      evaluated by determining the percentage of subjects in the therapeutic range (10
      20 mg/L). RESULTS: A 2-compartment model with between-subject variability on
      clearance (CL), central volume of distribution (Vc), and peripheral volume of
      distribution best fit the data. Blood urea nitrogen, age, creatinine clearance,
      and hemodialysis status were significant covariates on clearance. Hemodialysis
      status was a significant covariate on Vc and peripheral volume of distribution.
      In the final model, creatinine clearance was retained as a covariate on CL
      whereas hemodialysis status was retained as covariate on both CL and Vc. Using
      Monte Carlo simulations, the current nomogram was optimized by the addition of a
      loading dose and reducing the maintenance doses. The current nomogram is
      suboptimal. Optimization of the nomogram resulted in >40% subjects consistently
      being in the therapeutic range at troughs collected after the first 6 doses.
      CONCLUSIONS: CL and Vc differ markedly between patients undergoing hemodialysis
      and those not undergoing hemodialysis. Dosing nomogram based on these covariate
      relationships may potentially help in accurate dosing of vancomycin.

PMID- 29470228
TI  - Amiodarone Rifampicin Drug-Drug Interaction Management With Therapeutic Drug
      Monitoring.
AB  - The authors present a case of a 69-year-old man with arrhythmogenic right
      ventricular cardiomyopathy controlled with amiodarone and an infected orthopedic
      prosthesis requiring treatment with rifampicin. This combination involves a
      pharmacokinetic drug-drug interaction leading to subtherapeutic drug
      concentrations of amiodarone and its active metabolite. The long half-life of
      amiodarone and its active metabolite in combination with the late onset and
      offset of cytochrome P4503A (CYP3A4) induction by rifampicin makes this a
      challenging drug-drug interaction to cope with in clinical practice. Before,
      during, and after rifampicin treatment, the serum concentrations of amiodarone
      and its active metabolite were measured and the amiodarone dose was adjusted
      accordingly. The amiodarone dose required to maintain effective concentrations
      was 450% of the initial dose. The drug-drug interaction between amiodarone and
      rifampicin is relevant, both clinically and pharmacokinetically, and can be
      managed by dose adjustments of amiodarone based on serum concentrations.

PMID- 29470229
TI  - Three-Year Changes in Physical Activity and Subsequent Loss of Ability to Walk
      400 m in Older Adults: The InCHIANTI Study.
AB  - We examined the associations of maintaining or increasing physical activity (PA)
      for a 3-yr follow-up with subsequent incident inability to complete the 400-m
      walk test (i.e., mobility disability) for 6 yrs of follow-up in older adults.
      This study included 421 participants 65 yrs and older. The 400-m walk test was
      assessed at baseline and at 3-, 6-, and 9-yr follow-up. Physical activity was
      self-reported through a 6-point rating scale at baseline and 3-yr follow-up.
      Three-year cumulative PA (i.e., average at baseline and at 3-yr follow-up) and
      its changes (i.e., from baseline to 3-yr follow-up) were linked to subsequent
      incidence of mobility disability for 6 yrs of follow-up (i.e., from 3- to 9-yr
      follow-up), after adjustment for potential covariates. After the 3-yr period,
      incidence of mobility disability for the subsequent 6 yrs of follow-up occurred
      in 129 participants. The odds ratio (95% confidence interval) of incident
      mobility disability associated with 1-category increase in cumulative PA was 0.63
      (0.41-0.97, P = 0.036). The odds ratio (95% confidence interval) of incident
      mobility disability associated with 1-category increase in changes in PA was 0.56
      (0.38-0.84, P = 0.005). Hence, maintaining or increasing PA levels is associated
      with a reduced risk of mobility disability among older adults.

PMID- 29470230
TI  - Patients With Limited Health Literacy Have Similar Preferences but Different
      Perceptions in Surgical Decision-making for Carpal Tunnel Release.
AB  - BACKGROUND: Health literacy is the ability to obtain, process, and understand
      health information needed to make appropriate health decisions. The proper
      comprehension by patients regarding a given disease, its treatment, and the
      physician's instructions plays an important role in shared decision-making.
      Studies have disagreed over the degree to which differences in health literacy
      affect patients' preferences for shared decision-making; we therefore sought to
      evaluate this in the context of shared decision-making about carpal tunnel
      release. QUESTIONS/PURPOSES: (1) Do patients with limited health literacy have
      different preferences of shared decision-making for carpal tunnel release than
      those with greater levels of health literacy? (2) How do patients with limited
      health literacy retrospectively perceive their role in shared decision-making
      after carpal tunnel release? METHODS: Over a 32-month period, one surgeon
      surgically treated 149 patients for carpal tunnel syndrome. Patients were
      eligible if they had cognitive and language function to provide informed consent
      and complete a self-reported questionnaire and were not eligible if they had
      nerve entrapment other than carpal tunnel release or had workers compensation
      issues; based on those, 140 (94%) were approached for study. Of those, seven (5%)
      were lost to followup before 6 months, leaving 133 for analysis here. Their mean
      age was 55 years (range, 31-76 years), and 83% (111 of 133) were women. Thirty
      three percent (44 of 133) of patients had less than a high school education.
      Health literacy was measured according to the Newest Vital Sign during the
      initial visit, and a score of <= 3 was considered limited health literacy. Forty
      four percent of patients had limited health literacy. The Control Preferences
      Scale was used for patients to indicate their preferred role in surgical decision
      making preoperatively and to assess their perceived level of involvement
      postoperatively. Bivariate and multivariable analyses were performed to determine
      whether patients' clinical, demographic, and health literacy factors accounted
      for the preoperative preferences and postoperative assessments of their role in
      shared decision-making. A total of 133 patients would provide 94% power for a
      medium effect size for linear regression with five main predictors. RESULTS: We
      found no differences between patients with lower levels of health literacy and
      those with greater health literacy in terms of preferences of shared decision
      making for carpal tunnel release (3.0 +/- 1.6 versus 2.7 +/- 1.4; mean
      difference, 0.3; 95% confidence interval, -0.2 to 0.8; p = 0.25). A history of
      surgical procedures (coefficient = -0.32, p < 0.01) and a lower Disabilities of
      the Arm, Shoulder and Hand score (coefficient = 0.17, p = 0.02) were
      independently associated with a preference for an active role in shared decision
      making. However, patients with limited health literacy (coefficient = -0.31, p =
      0.01) and an absence of a caregiver (coefficient = -0.28, p = 0.03) perceived a
      more passive role in actual decision-making. CONCLUSIONS: Physicians should be
      aware of the discrepancy between preferences and perceptions of shared decision
      making among patients with limited health literacy, and physicians should
      consider providing a decision aid tailored to basic levels of health literacy to
      help patients achieve their preferred role in decision-making. LEVEL OF EVIDENCE:
      Level II, prognostic study.

PMID- 29470231
TI  - Classifications in Brief: The Pipkin Classification of Femoral Head Fractures.

PMID- 29470232
TI  - Intraoperative Extracorporeal Irradiation and Frozen Treatment on Tumor-bearing
      Autografts Show Equivalent Outcomes for Biologic Reconstruction.
AB  - BACKGROUND: Immediately recycling the resected bone segment in a biologic limb
      salvage reconstruction is an option after wide resection of bone. Intraoperative
      extracorporeal irradiation and freezing are the two major tumor-killing
      techniques applied on the fresh tumor-bearing autografts. However, graft-derived
      tumor recurrence and complications are concerns affecting graft survival.
      QUESTIONS/PURPOSES: We therefore asked: (1) Is there a difference in the
      proportion of patients achieving union by 18 months after surgery between the
      groups with extracorporeal-irradiated autografts and frozen-treated autografts?
      (2) Is there any difference in the frequency of graft-related complications for
      patients receiving either an extracorporeal-irradiated or a frozen-treated
      autograft? (3) Is there a difference between the techniques in terms of graft
      derived recurrence? (4) Are there differences in failure-free grafts, and limb
      and overall survivorship between autografts treated by extracorporeal irradiation
      or by freezing? METHODS: During the study period we treated a total of 333
      patients with high-grade osteosarcoma. One hundred sixty-nine patients were
      excluded. Overall, 79 of the enrolled 164 patients received recycled autografts
      treated with extracorporeal irradiation whereas the other 85 received frozen
      treated autografts. The mean followup was 82 +/- 54 months for the extracorporeal
      irradiation group and 70 +/- 25 months for the frozen autograft group, and one
      patient was lost to followup. Complications and graft failure (revision required
      for primary graft removal) were characterized by adapting the International
      Society of Limb Society (ISOLS) system modified for inclusion of biologic and
      expandable reconstruction. The primary study endpoints were the proportion of
      patients in each group who achieved radiographic union, and had an ISOLS grade of
      fair or good host graft fusion at 6, 9, 12, and 18 months after surgery. Five
      year survival data for graft failure and limb amputation were analyzed by a
      cumulative incidence function regression model whereas the Kaplan-Meier function
      was used to test the 5-year overall survival rate between the two techniques.
      RESULTS: With the numbers available, no differences were found in the accumulated
      proportion of patients achieving union between the groups at 6, 9, 12, and 18
      months. Radiographic evaluation did not show differences in the average scores of
      compared criteria. However in the subchondral bone subcriterion, more patients
      receiving frozen-treated autografts had higher scores (p = 0.03). Complications
      leading to a second surgery were not different between extracorporeal irradiation
      and frozen autografts in aspects of soft tissue failure (Type 1B), nonunion (Type
      2B), structural failure (Type 3A and Type 3B), or infection (Type 4A and Type
      4B). No graft-originating tumor recurrence was found and there was no difference
      in Type 5A tumor progression originating from soft tissue in the groups (odds
      ratio, 0.8; 95% CI, 0.3-2.1; p = 0.7). Neither group showed a difference in the
      cumulative incidence for graft failure and limb amputation. Five-year overall
      survival rates were 83% and 84% (p = 0.69) for extracorporeal-irradiated and
      frozen autografts respectively. A decrease in survivorship was seen at 50 to 100
      months after surgery for the extracorporeal irradiation group. CONCLUSION: We
      segregated the ISOLS criteria evaluating the graft-mediated tumor progression
      into host- or graft-derived complications (Types 5B and 5C) in this study. With
      the available data, there was no difference in the incidence of tumor recurrence
      derived from irradiation- or frozen-treated autografts. Ongoing evaluations
      comparing 10-year survivorship for both groups will be helpful to elucidate the
      possible difference found after 100 months. LEVEL OF EVIDENCE LEVEL: III,
      therapeutic study.

PMID- 29470233
TI  - Can a Nomogram Help to Predict the Overall and Cancer-specific Survival of
      Patients With Chondrosarcoma?
AB  - BACKGROUND: Many factors have been reported to be associated with the prognosis
      of patients with chondrosarcoma, but clinicians have few tools to estimate
      precisely an individual patient's likelihood of surviving the illness. We
      therefore sought to develop effective nomograms to better estimate the survival
      of patients with chondrosarcoma. QUESTIONS/PURPOSES: (1) Which clinicopathologic
      features are independent prognostic factors for patients with chondrosarcoma? (2)
      Can we develop a nomogram to predict 3- and 5-year overall and cancer-specific
      survival of individual patients with chondrosarcoma based on personalized
      information? METHODS: We collected information on patients diagnosed with
      chondrosarcoma between 1988 and 2011 from the Surveillance, Epidemiology, and End
      Results (SEER) database. The SEER database consists of 18 cancer registries and
      covers approximately 30% of the total United States population. One thousand
      thirty-four adult patients with grade II or III chondrosarcoma were included in
      the cohort (patients with grade I chondrosarcoma were not evaluated in this
      study), while 327 patients were excluded from the study owing to missing data
      regarding tumor size or metastasis. Nine hundred nineteen patients (89%) in the
      cohort had complete followup for at least 1 year. The X-tile program was used to
      determine optimal cutoff points. Univariate and multivariate analyses were
      applied to identify independent factors that were further included in the
      nomograms predicting 3- and 5-year overall survival and cancer-specific survival.
      Records of 1034 patients were collected and randomly divided into training (n =
      517) and validation (n = 517) cohorts. The nomograms were developed based on
      training cohort. Data for the training cohort were obtained for internal
      validation of the nomograms, whereas data for the validation cohort were obtained
      for external validation of the nomograms. Bootstrapped validation, which used a
      resample with 500 iterations, was applied to validate the nomograms internally
      and externally. RESULTS: Six independent prognostic factors for overall survival
      and six for cancer-specific survival were identified and incorporated to
      construct nomograms for 3- and 5-year overall and cancer-specific survival. These
      nomograms can easily be used by providers in the office to estimate a patient's
      prognosis; the only clinical details a provider needs to use these nomograms
      effectively are age, histologic subtype, tumor grade, whether surgery was
      performed, tumor size, and the presence or absence of metastases. Internal and
      external calibration plots for the probability of 3- and 5-year overall survival
      and cancer-specific survival showed good agreement between nomogram prediction
      and observed outcomes. The concordance indices (C-indices) for internal
      validation of overall survival and cancer-specific survival prediction were 0.803
      and 0.829, respectively, whereas the C-indices for external validation were 0.753
      and 0.759, respectively. CONCLUSIONS: We were able to develop effective nomograms
      to predict overall survival and cancer-specific survival for patients with
      chondrosarcoma; these nomograms require only basic information, which should be
      available to all providers in the office setting. If these observations can be
      validated in different registries or databases, the nomograms can assist
      clinicians in counseling patients regarding therapeutic choices. LEVEL OF
      EVIDENCE: Level III, prognostic study.

PMID- 29470234
TI  - Incidence of Neuraxial Abnormalities Is Approximately 8% Among Patients With
      Adolescent Idiopathic Scoliosis: A Meta-analysis.
AB  - BACKGROUND: Several studies have sought to address the role of routine
      preoperative MRI in patients with adolescent idiopathic scoliosis (AIS)
      undergoing deformity correction. Despite similar results regarding the prevalence
      of neuraxial anomalies detected on MRI, published conclusions conflict and give
      opposing recommendations. Lack of consensus has led to important variations in
      use of MRI before spinal surgery for patients with AIS. QUESTIONS/PURPOSES: This
      systematic review and meta-analysis of studies about patients with AIS evaluated
      (1) the overall proportion of neuraxial abnormalities; (2) the patient factors
      and curve characteristics that may be associated with abnormalities; and (3) the
      proportion of patients who underwent neurosurgical intervention before scoliosis
      surgery and the kinds of neuraxial lesions that were identified. METHODS: We
      performed a search of four electronic databases (PubMed, EMBASE, CINAHL Plus, and
      SCOPUS) utilizing search terms related to routine MRI and AIS, yielding 206
      articles. Studies included had at least 20 participants, patients with ages 11 to
      21 years, and a Methodological Index for Non-Randomized Studies (MINORS) study
      quality score of 8 and 16 points for noncomparative and comparative studies,
      respectively. Non-English manuscripts, animal studies, and those that did not
      include patients with AIS solely were excluded. Eighteen articles with 4746
      patients were included for analysis of the overall proportion of neuraxial
      abnormalities, 12 articles with 3028 patients for analysis by sex, eight articles
      with 1603 patients for right main thoracic curve, eight articles with 665
      patients for a left main thoracic curve, and 13 articles with 3063 patients and
      230 (7.5%) abnormalities for number of neurosurgical interventions before
      scoliosis correction. The mean MINORS score for studies included was 14 (range,
      10-20). Each study was analyzed for the proportion of patients identified with
      neuraxial abnormalities and associations with specific demographics. We
      determined the proportion of patients who underwent surgical interventions before
      scoliosis surgery as well as the types of neuraxial lesions identified. The
      articles were assessed for heterogeneity and publication bias. Because all groups
      were determined to be heterogeneous, a random-effects model was used for each
      group in this meta-analysis; with this analysis, an overlap of 95% confidence
      intervals suggests no difference at the p < 0.05 level, but this analytic
      approach does not provide p values. RESULTS: The pooled proportion of neuraxial
      abnormalities detected on MRI was 8% (95% confidence interval [CI], 6%-12%). With
      the numbers available, we found no difference in the proportion of male and
      female patients with neuraxial abnormalities (18% [95% CI, 11%-29%] versus 9%
      [95% CI, 6%-12%], respectively). Likewise, there was no difference in the
      proportion of pooled neuraxial abnormalities in right and left curves (9% [95%
      CI, 6%-14%] versus 15% [95% CI, 5%-35%], respectively). In the subset of
      abnormalities analyzed for number of neurosurgical interventions before scoliosis
      correction, the pooled proportion showed that 33% (95% CI, 24%-43%) underwent
      neurosurgical intervention before deformity correction. The most common
      abnormalities of the 367 found on MRI were syringomyelia in 127 patients (35%),
      Arnold-Chiari Type 1 malformation with syrinx in 103 patients (28%), and isolated
      Arnold-Chiari Type 1 malformation in 91 patients (25%). CONCLUSIONS: The
      proportion of patients with AIS who have neuraxial abnormalities is high (8%) and
      a large number undergo surgical intervention before scoliosis reconstruction. We
      did not find any particular demographic variables that indicated an increased
      risk of abnormality. Clinicians should consider advanced imaging before surgical
      intervention in the treatment of a patient with an idiopathic diagnosis.
      Preventable variables need to be identified by future studies to establish a
      better working treatment protocol for these patients. LEVEL OF EVIDENCE: Level
      III, diagnostic study.

PMID- 29470235
TI  - Is Climate Associated With Revision for Prosthetic Joint Infection After Primary
      TKA?
AB  - BACKGROUND: Climate factors have been shown to be associated with spontaneous
      musculoskeletal and some surgical site infections with increased rates of
      infection during warmer periods. To date, little research has been performed to
      determine if this phenomenon is associated with differences in the risk of
      revision for prosthetic joint infection (PJI) in primary TKA. QUESTIONS/PURPOSES:
      (1) Does the rate of revision for early PJI within the first year after primary
      TKA differ between tropical and nontropical regions? (2) Is there a seasonal
      variation in the rate of revision for PJI? (3) Is the geographic and seasonal
      variation (if present) associated with the sex, age, and/or American Society of
      Anesthesiologists (ASA) grade of the patient? METHODS: All 219,983 primary TKAs
      performed for osteoarthritis over a 5-year period (2011-2015) in the Australian
      Orthopaedic Association National Joint Replacement Registry were examined based
      on the month of the primary procedure to determine the rate of revision for PJI
      within 12 months. The data were analyzed to determine the differences in the risk
      of revision for PJI based on geographic region and season of the primary
      procedure adjusting for sex, age, and ASA grade of the patient. RESULTS: The
      early revision rate for PJI was higher in the tropical compared with the
      nontropical region of Australia (0.73% versus 0.37%; odds ratio [OR], 1.87; 95%
      confidence interval [CI], 1.44-2.42; p < 0.001). The tropical region of Australia
      demonstrated a seasonal variation in the rate of revision for PJI with a higher
      rate during the warmer monsoon wet season of summer and fall (summer/fall 0.98%
      versus winter/spring 0.51%; OR, 1.88; 95% CI, 1.12-3.16; p = 0.02). A seasonal
      variation was not seen in the nontropical region (OR, 1.03; 95% CI, 0.90-1.19; p
      = 0.64). The regional and seasonal changes were independent of sex, age, and ASA
      grade. CONCLUSIONS: Climate factors are associated with the risk of early
      revision for PJI in patients undergoing primary TKA with rates of such revisions
      approximately double in tropical regions compared with nontropical regions.
      Additionally, tropical regions demonstrate a seasonal variation with the risk of
      PJI doubling during the warmer, monsoonal wet season of summer and fall. These
      findings should be confirmed in further studies that can better control for
      possible confounding variables. The mechanism for this phenomenon is not clear,
      and further research into this subject is also indicated. LEVEL OF EVIDENCE:
      Level III, therapeutic study.

PMID- 29470236
TI  - Is the Lesser Trochanter Profile a Reliable Means of Restoring Anatomic Rotation
      After Femur Fracture Fixation?
AB  - BACKGROUND: Restoring normal femoral rotation is an important consideration when
      managing femur fractures. Femoral malrotation after fixation is common and
      several preventive techniques have been described. Use of the lesser trochanter
      profile is a simple method to prevent malrotation, because the profile changes
      with femoral rotation, but the accuracy of this method is unclear.
      QUESTIONS/PURPOSES: The purposes of this study were (1) to report the rotational
      profiles of uninjured femora in an adult population; and (2) to determine if the
      lesser trochanter profile was associated with variability in femoral rotation.
      METHODS: One hundred fifty-five consecutive patients (72% female and 28% male)
      with a mean age of 32 years (range, 12-56 years) with a CT scanogram were
      retrospectively evaluated. Patients were included if CT scanograms had adequate
      cuts of the proximal and distal femur. Patients were excluded if they had prior
      hip/femur surgery or anatomic abnormalities of the proximal femur. CT scanogram
      measurements of femoral rotation were compared with the lesser trochanter profile
      (distance from the tip of the lesser trochanter to the medial cortex of the
      femur) measured on weightbearing AP radiographs. These measurements were made by
      a single fellowship-trained orthopaedic surgeon and repeated for intraobserver
      reliability testing. Presence of rotational differences based on sex and
      laterality was assessed and correlation of the difference in lesser trochanter
      profile to the difference in femoral rotation was determined using a coefficient
      of determination (r). RESULTS: The mean femoral rotation was 10.9 degrees  (SD +/
      8.8 degrees ) of anteversion. Mean right femoral rotation was 11.0 degrees  (SD
      +/- 8.9 degrees ) and mean left femoral rotation was 10.7 degrees  (SD +/- 8.7
      degrees ) with a mean difference of 0.3 degrees  (95% confidence interval [CI], 
      1.7 degrees  to 2.3 degrees ; p = 0.76). Males had a mean rotation of 9.4 degrees
      (SD +/- 7.7 degrees ) and females had a mean rotation of 11.5 degrees  (SD +/-
      9.1 degrees ) with a mean difference of 2.1 degrees  (95% CI, -0.1 degrees  to
      4.3 degrees ; p = 0.06). Mean lesser trochanter profile was 6.6 mm (SD +/- 4.0
      mm). Mean right lesser trochanter profile was 6.6 mm (SD +/- 3.9 mm) and mean
      left lesser trochanter profile was 6.5 mm (SD +/- 4.0 mm) with a mean difference
      of 0.1 mm (-0.8 mm to 1.0 mm, p = 0.86). The lesser trochanter profile varied
      between the sexes; males had a mean of 8.3 mm (SD +/- 3.4), and females had a
      mean of 5.9 mm (SD +/- 4.0). The mean difference between sexes was 2.5 mm (1.5
      3.4 mm; p < 0.001). The magnitude of the lesser trochanter profile measurement
      and degree of femoral rotation were positively correlated such that increasing
      measures of the lesser trochanter profile were associated with increasing amounts
      of femoral anteversion. The lesser trochanter profile was associated with femoral
      version in a linear regression model (r = 0.64; p < 0.001). Thus, 64% of the
      difference in femoral rotation can be explained by the difference in the lesser
      trochanter profile. Intraobserver reliability for both the femoral version and
      lesser trochanter profile was noted to be excellent with intraclass correlation
      coefficients of 0.94 and 0.95, respectively. CONCLUSIONS: This study helps define
      the normal femoral rotation profile among adults without femoral injury or bone
      deformity and demonstrated no rotational differences between sexes. The lesser
      trochanter profile was found to be positively associated with femoral rotation.
      Increasing and decreasing lesser trochanter profile measurements are associated
      with increasing and decreasing amounts of femoral rotation, respectively.
      CLINICAL RELEVANCE: The lesser trochanter profile can determine the position of
      the femur in both anteversion and retroversion, supporting its use as a method to
      restore preinjury femoral rotation after fracture fixation. Although some
      variability in the rotation between sides may exist, matching the lesser
      trochanter profile between injured and uninjured femora can help reestablish
      native rotation.

PMID- 29470237
TI  - Primary Shoulder Hemiarthroplasty: What Can Be Learned From 359 Cases That Were
      Surgically Revised?
AB  - BACKGROUND: Primary shoulder hemiarthroplasty is used to address a range of
      glenohumeral disorders, including fracture, arthritis, avascular necrosis, and
      capsulorrhaphy arthropathy; some patients with hemiarthroplasties undergo
      revision surgery for persistent pain or residual shoulder dysfunction. The
      literature does not clarify the features of the hemiarthroplasties having repeat
      surgery in a way that can guide surgeons' efforts to minimize the need for
      revision. To help address this gap, we analyzed the characteristics of patients
      from our region for whom we performed surgical revision of a prior humeral
      hemiarthroplasty QUESTIONS/PURPOSES: (1) What are the common characteristics of
      shoulder hemiarthroplasties having a revision? (2) What are the common
      characteristics of the subset of revised shoulder hemiarthroplasties that were
      performed for fracture? (3) What are characteristics of the subset of all revised
      hemiarthroplasties that were associated with glenoid bone erosion? METHODS: Data
      for 983 patients for whom we performed a surgical revision of any type of
      shoulder arthroplasty between January 1991 and January 2017 were identified in
      our longitudinally maintained institutional arthroplasty revision database. In
      each case, revision had been elected by shared patient and surgeon decision
      making after consideration of the disorder, degree of compromised comfort and
      function, treatment alternatives, and the risks of surgery. Of these 983
      patients, 359 (37%) had a revision of a prior primary hemiarthroplasty; these
      patients were the subjects of this investigation. In this group of patients, we
      investigated the patient demographics, shoulder characteristics, prerevision
      radiographic findings, and findings at revision surgery. No patients were
      excluded. The patients having revision of primary hemiarthroplasties had severe
      loss of self-assessed shoulder comfort and function, with Simple Shoulder Test
      (SST) scores averaging 2.2 +/- 2.2 of the maximum score of 12. The majority of
      these patients (81%) were women. The medical records of these 359 patients were
      abstracted to determine the diagnosis for the index primary hemiarthroplasty,
      clinical characteristics before surgery, and findings at surgical revision. One
      hundred twelve of the arthroplasties had been performed for fracture-related
      diagnoses; a subgroup analysis was performed on these patients. Two hundred
      seventy-three of the 359 patients (76%) had plain radiographs performed within 3
      months before revision surgery that were adequate for assessing the radiographic
      characteristics of the glenoid, humerus, humeral component, and glenohumeral
      relationships; a subgroup analysis was performed on these patients. The degree of
      glenoid erosion was measured by a single observer in accordance with established
      criteria: Grade 1 is no erosion, Grade 2 is erosion limited to subchondral bone,
      Grade 3 is moderate erosion with medialization, and Grade 4 is medialization
      beyond the coracoid base. Some patients were included in both of these subgroups.
      RESULTS: Common characteristics of the revised hemiarthroplasties included female
      sex (81%), rotator cuff (89 of 359; 25%) or subscapularis (81 of 359; 23%)
      failure, problems related to prior fracture (154 of 359; 43%), glenoid erosion
      125 of 359; 35%), and component malposition (89 of 359; 25%). Hemiarthroplasties
      performed for fracture-related problems often were associated with tuberosity
      malunion or nonunion (58 of 79; 73%) and decentering of the humeral component on
      the glenoid surface (45 of 71; 63%). Major erosion of the bony glenoid (Grade 3
      or 4) was more common in decentered hemiarthroplasties (42 of 102; 41%) than for
      centered hemiarthroplasties (36 of 146; 25%) (Fisher's exact p = 0.008) and more
      common for hemiarthroplasties positioned in valgus (28 of 50; 56%) than for those
      positioned in neutral or varus (40 of 188; 21%) (Fishers' exact p < 0.0001).
      CONCLUSIONS: These findings suggest that some revisions of primary
      hemiarthroplasties may be avoided by surgical techniques directed at centering
      the prosthetic humeral articular surface on the glenoid concavity using proper
      humeral component positioning and soft tissue balance, by avoiding valgus
      positioning of the humeral component, and by managing glenoid disorders with a
      primary glenohumeral arthroplasty rather than a hemiarthroplasty alone. When
      durable security of the subscapularis, rotator cuff, and tuberosities is in
      question, the surgeon may consider a reverse total shoulder arthroplasty. LEVEL
      OF EVIDENCE: Level III, therapeutic study.

PMID- 29470239
TI  - Reply to the Letter to the Editor: Editorial: Do Orthopaedic Surgeons Belong on
      the Sidelines at American Football Games?

PMID- 29470238
TI  - CORR Insights(r): Tenosynovial Giant Cell Tumors in Children: A Similar Entity
      Compared With Adults.

PMID- 29470240
TI  - Letter to the Editor: Pearls: The Mobile Segment in Sarcoma Resections.

PMID- 29470241
TI  - CORR Insights(r): Intrawound Antibiotic Powder Decreases Frequency of Deep
      Infection and Severity of Heterotopic Ossification in Combat Lower Extremity
      Amputations.

PMID- 29470242
TI  - CORR Insights(r): Primary Shoulder Hemiarthroplasty: What Can Be Learned From 359
      Cases That Were Surgically Revised?

PMID- 29470243
TI  - Reply to the Letter to the Editor Obesity Epidemic: Is Its Impact on Total Joint
      Arthroplasty Underestimated? An Analysis of National Trends.

PMID- 29470244
TI  - CORR Insights(r): Do Stem Design and Surgical Approach Influence Early Aseptic
      Loosening in Cementless THA?

PMID- 29470245
TI  - Intra-Aortic Balloon Pump Use Before Left Ventricular Assist Device Implantation:
      Insights From the INTERMACS Registry.
AB  - Use of durable, continuous-flow left ventricular assist devices (LVADs) has
      expanded rapidly, although data are limited regarding optimization strategies
      before LVAD implantation. We examined current use of intra-aortic balloon pumps
      (IABPs) before LVAD implantation and compared outcomes of patients with IABP use
      to those without. We analyzed data from the Interagency Registry for Mechanical
      Assisted Circulatory Support (INTERMACS) on patients who underwent LVAD
      implantation between 2006 and 2014. We limited the analysis to patients with an
      admitting diagnosis of LVAD placement. The primary exposure was IABP use within
      48 hours before LVAD implantation. We used propensity scores to compare 30 day
      postoperative outcomes to reduce treatment selection bias. Of 2,446 patients, 433
      (18%) received an IABP before LVAD placement. Patients with IABP use, compared
      with those without, had markers of more advanced disease, including worse renal
      and liver function, worse right ventricular function, and use of mechanical
      ventilation (p < 0.05 for all comparisons). A composite outcome of post-operative
      right heart failure, hepatic dysfunction, renal dysfunction, or death occurred in
      83 (19.2%) patients with IABP use, compared with 342 (17.1%) patients without
      IABP use (unadjusted hazard ratio, 1.13; 95% confidence interval, 0.89-1.44;
      adjusted hazard ratio, 1.02; 95% confidence interval, 0.78-1.33). IABP use before
      LVAD placement was common. Despite markers of higher risk in patients with IABP
      use, we found no significant difference in 30 day outcomes compared to those
      without. The results suggest that IABP use may mitigate risk of early
      postoperative adverse outcomes in select patients.

PMID- 29470246
TI  - Design and Evaluation of a Structural Reinforced Small Intestinal Submucosa
      Vascular Graft for Hemodialysis Access in a Porcine Model.
AB  - Synthetic vascular access for hemodialysis exhibits biological and mechanical
      material properties mismatch with the native vessels. These limitations prevent
      infiltration of endothelial cells and decrease grafts long-term patency,
      particularly in small diameter vessels. We aimed to design a curved structural
      reinforced small intestinal submucosa (SIS) vascular graft for hemodialysis
      access and to evaluate in a porcine animal model graft patency by Doppler
      ultrasonography, tissue remodeling by histology, and vascular wall Young's
      modulus after implantation by biaxial tensile test. Curved 4 mm inner diameter,
      0.5 mm thickness, and 150 mm length SIS grafts were designed. Small intestinal
      submucosa vascular grafts were preliminary tested in vivo in a porcine animal
      model (n=3) constructing an arteriovenous fistula between the carotid artery and
      the jugular vein; GORE-TEX grafts were implanted as control. Small intestinal
      submucosa grafts remained patent 46 +/- 7 days against the control, 30 +/- 3
      days. Histology showed thrombus formation on the lumen (80% to 100% surface area)
      of all explanted grafts. Small intestinal submucosa grafts exhibited
      neovascularization and endothelial cells alignment on the graft wall, indicating
      regeneration. Biaxial tensile tests demonstrated no significant differences in
      Young's moduli between SIS grafts (ECirc = 2.5 +/- 1.0 MPa, ELong = 5.7 +/- 2.6
      MPa) and native artery (ECirc = 1.4 +/- 0.8 MPa, ELong = 5.5 +/- 1.1 MPa),
      indicating similar wall stiffness. This study proposes an innovative design of a
      tissue-engineered vascular graft for hemodialysis access that, besides its
      structural characteristics similar to those of current synthetic grafts, could
      enhance biological performance because of its composition.

PMID- 29470247
TI  - Hypofibrinogenemia Is Associated With Poor Outcome and Secondary Hemophagocytic
      Lymphohistiocytosis/Macrophage Activation Syndrome in Pediatric Severe Sepsis.
AB  - OBJECTIVES: Some children with sepsis exhibit a sustained hyperinflammatory
      response that can trigger secondary hemophagocytic lymphohistiocytosis/macrophage
      activation syndrome. Although hypofibrinogenemia is a shared feature of sepsis
      and hemophagocytic lymphohistiocytosis, there are no data about fibrinogen as a
      biomarker to identify children with sepsis/secondary hemophagocytic
      lymphohistiocytosis/macrophage activation syndrome overlap. We hypothesized that
      hypofibrinogenemia is associated with poor outcomes and secondary hemophagocytic
      lymphohistiocytosis/macrophage activation syndrome and has utility as a screening
      biomarker for this sepsis phenotype. DESIGN: A retrospective cohort study of
      patients less than or equal to 21 years treated for severe sepsis from January
      2012 to December 2014. SETTING: Emergency department and PICU at a single
      academic children's hospital. PATIENTS: Consecutive patients with greater than or
      equal to one episode of hypofibrinogenemia (serum fibrinogen < 150 mg/dL) within
      7 days of sepsis were compared with a random sample of patients without
      hypofibrinogenemia using an a priori sample size target of 190. Thirty-eight
      patients with hypofibrinogenemia were compared with 154 without
      hypofibrinogenemia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The
      primary outcome was "complicated course" (composite of 28-d mortality or >= two
      organ failures at 7 d). Secondary outcomes were 28-day mortality and fulfillment
      of diagnostic criteria for secondary hemophagocytic
      lymphohistiocytosis/macrophage activation syndrome. We used Wilcoxon rank-sum,
      Fisher exact test, and multivariable logistic regression to compare patients with
      versus without hypofibrinogenemia. Patients with hypofibrinogenemia were more
      likely to have a complicated course (73.7% vs 29.2%; p < 0.001), 28-day mortality
      (26.3% vs 7.1%, p = 0.002), and meet diagnostic criteria for secondary
      hemophagocytic lymphohistiocytosis/macrophage activation syndrome (21.1% vs 1.3%;
      p < 0.001). After controlling for confounders, hypofibrinogenemia remained
      associated with complicated course (adjusted odds ratio, 8.8; 95% CI, 3.5-22.4),
      mortality (adjusted odds ratio, 6.0; 95% CI, 2.0-18.1), and secondary
      hemophagocytic lymphohistiocytosis/macrophage activation syndrome (adjusted odds
      ratio, 27.6; 95% CI, 4.4-173). CONCLUSIONS: Hypofibrinogenemia was independently
      associated with poor outcome and secondary hemophagocytic
      lymphohistiocytosis/macrophage activation syndrome in pediatric sepsis.
      Measurement of fibrinogen may provide a pragmatic biomarker to identify children
      with possible sepsis/secondary hemophagocytic lymphohistiocytosis/macrophage
      activation syndrome overlap for whom further diagnostic testing and consideration
      of adjunctive immunomodulatory therapies should be considered.

PMID- 29470248
TI  - Role of cardiovascular imaging in cardiac resynchronization therapy: a literature
      review.
AB  - : Cardiac resynchronization therapy (CRT) is an established treatment in patients
      with symptomatic drug-refractory heart failure and broad QRS complex on the
      surface ECG. Despite the presence of either mechanical dyssynchrony or viable
      myocardium at the site where delivering left ventricular pacing being necessary
      conditions for a successful CRT, their direct assessment by techniques of
      cardiovascular imaging, though feasible, is not recommended in clinical practice
      by the current guidelines. Indeed, even though there is growing body of data
      providing evidence of the additional value of an image-based approach as compared
      with routine approach in improving response to CRT, these results should be
      confirmed in prospective and large multicentre trials before their impact on CRT
      guidelines is considered.

PMID- 29470249
TI  - Elevated serum uric acid affects myocardial reperfusion and infarct size in
      patients with ST-segment elevation myocardial infarction undergoing primary
      percutaneous coronary intervention.
AB  - AIMS: Elevated serum uric acid (eSUA) was associated with unfavorable outcome in
      patients with ST-segment elevation myocardial infarction (STEMI). However, the
      effect of eSUA on myocardial reperfusion injury and infarct size has been poorly
      investigated. Our aim was to correlate eSUA with infarct size, infarct size
      shrinkage, myocardial reperfusion grade and long-term mortality in STEMI patients
      undergoing primary percutaneous coronary intervention. METHODS: We performed a
      post-hoc patients-level analysis of two randomized controlled trials, testing
      strategies for myocardial ischemia/reperfusion injury protection. Each patient
      underwent acute (3-5 days) and follow-up (4-6 months) cardiac magnetic resonance.
      Infarct size and infarct size shrinkage were outcomes of interest. We assessed T2
      weighted edema, myocardial blush grade (MBG), corrected Thrombolysis in
      myocardial infarction Frame Count, ST-segment resolution and long-term all-cause
      mortality. RESULTS: A total of 101 (86.1% anterior) STEMI patients were included;
      eSUA was found in 16 (15.8%) patients. Infarct size was larger in eSUA compared
      with non-eSUA patients (42.3 +/- 22 vs. 29.1 +/- 15 ml, P = 0.008). After
      adjusting for covariates, infarct size was 10.3 ml (95% confidence interval 1.2
      19.3 ml, P = 0.001) larger in eSUA. Among patients with anterior myocardial
      infarction the difference in delayed enhancement between groups was maintained
      (respectively, 42.3 +/- 22.4 vs. 29.9 +/- 15.4 ml, P = 0.015). Infarct size
      shrinkage was similar between the groups. Compared with non-eSUA, eSUA patients
      had larger T2-weighted edema (53.8 vs. 41.2 ml, P = 0.031) and less favorable MBG
      (MBG < 2: 44.4 vs. 13.6%, P = 0.045). Corrected Thrombolysis in myocardial
      infarction Frame Count and ST-segment resolution did not significantly differ
      between the groups. At a median follow-up of 7.3 years, all-cause mortality was
      higher in the eSUA group (18.8 vs. 2.4%, P = 0.028). CONCLUSION: eSUA may affect
      myocardial reperfusion in patients with STEMI undergoing percutaneous coronary
      intervention and is associated with larger infarct size and higher long-term
      mortality.

PMID- 29470250
TI  - Clinically oriented device programming in bradycardia patients: part 1 (sinus
      node disease). Proposals from AIAC (Italian Association of Arrhythmology and
      Cardiac Pacing).
AB  - : Modern pacemakers have an increasing number of programable parameters and
      specific algorithms designed to optimize pacing therapy in relation to the
      individual characteristics of patients. When choosing the most appropriate
      pacemaker type and programing, the following variables must be taken into
      account: the type of bradyarrhythmia at the time of pacemaker implantation; the
      cardiac chamber requiring pacing, and the percentage of pacing actually needed to
      correct the rhythm disorder; the possible association of multiple rhythm
      disturbances and conduction diseases; the evolution of conduction disorders
      during follow-up. The goals of device programing are to preserve or restore the
      heart rate response to metabolic and hemodynamic demands; to maintain
      physiological conduction; to maximize device longevity; to detect, prevent, and
      treat atrial arrhythmia. In patients with sinus node disease, the optimal pacing
      mode is DDDR. Based on all the available evidence, in this setting, we consider
      appropriate the activation of the following algorithms: rate responsive function
      in patients with chronotropic incompetence; algorithms to maximize intrinsic
      atrioventricular conduction in the absence of atrioventricular blocks; mode
      switch algorithms; algorithms for autoadaptive management of the atrial pacing
      output; algorithms for the prevention and treatment of atrial tachyarrhythmias in
      the subgroup of patients with atrial tachyarrhythmias/atrial fibrillation. The
      purpose of this two-part consensus document is to provide specific suggestions
      (based on an extensive literature review) on appropriate pacemaker setting in
      relation to patients' clinical features.

PMID- 29470251
TI  - Clinically oriented device programming in bradycardia patients: part 2
      (atrioventricular blocks and neurally mediated syncope). Proposals from AIAC
      (Italian Association of Arrhythmology and Cardiac Pacing).
AB  - : The purpose of this two-part consensus document is to provide specific
      suggestions (based on an extensive literature review) on appropriate pacemaker
      setting in relation to patients' clinical features. In part 2, criteria for
      pacemaker choice and programming in atrioventricular blocks and neurally mediate
      syncope are proposed. The atrioventricular blocks can be paroxysmal or
      persistent, isolated or associated with sinus node disease. Neurally mediated
      syncope can be related to carotid sinus syndrome or cardioinhibitory vasovagal
      syncope. In sinus rhythm, with persistent atrioventricular block, we considered
      appropriate the activation of mode-switch algorithms, and algorithms for auto
      adaptive management of the ventricular pacing output. If the atrioventricular
      block is paroxysmal, in addition to algorithms mentioned above, algorithms to
      maximize intrinsic atrioventricular conduction should be activated. When sinus
      node disease is associated with atrioventricular block, the activation of rate
      responsive function in patients with chronotropic incompetence is appropriate. In
      permanent atrial fibrillation with atrioventricular block, algorithms for auto
      adaptive management of the ventricular pacing output should be activated. If the
      atrioventricular block is persistent, the activation of rate-responsive function
      is appropriate. In carotid sinus syndrome, adequate rate hysteresis should be
      programmed. In vasovagal syncope, specialized sensing and pacing algorithms
      designed for reflex syncope prevention should be activated.

PMID- 29470252
TI  - Multi and extensively drug-resistant pulmonary tuberculosis: advances in
      diagnosis and management.
AB  - PURPOSE OF REVIEW: Multidrug-resistant (MDR) tuberculosis (TB) and extensively
      drug-resistant (XDR)-TB epidemics are key obstacles towards TB control and
      elimination. RECENT FINDINGS: Diagnosis of MDR/XDR-TB is difficult and requires
      several weeks. New diagnostic tools are being tested and proposed allowing for
      shorter time to diagnosis and reduced delays in starting an adequate treatment
      regimen. MDR/XDR-TB treatment strategies are currently on an evolving stage. New
      shortened treatments based on the recommended 'Bangladesh regimen' or on the
      newer anti-TB drugs, delamanid and bedaquiline may represent part of the future
      scenario. In addition, more information on safety and efficacy of delamanid and
      bedaquiline has been published, allowing to better position these drugs. Recent
      information on treatment regimens for the paediatric age, with or without
      delamanid or bedaquiline, has become available. This is of great help in
      designing safer and more efficacious regimens for the treatment of MDR/XDR-TB in
      children and adolescents. SUMMARY: The accessibility, sustainability and scale-up
      of new diagnostic technologies are lagging behind and more efforts are needed. In
      addition, we need high-quality information on safety and efficacy of various
      combinations of drugs to obtain the best possible regimens to treat the largest
      possible proportion of patients.

PMID- 29470254
TI  - How can we improve clinical research in pneumonia?
AB  - PURPOSE OF REVIEW: The primary challenges in the field of clinical research
      include a lack of support within existing infrastructure, insufficient number of
      clinical research training programs and a paucity of qualified mentors. Most
      medical centers offer infrastructure support for investigators working with
      industry sponsors or government-funded clinical trials, yet there are a
      significant amount of clinical studies performed in the field of pneumonia which
      are observational studies. For this type of research, which is frequently
      unfunded, support is usually lacking. RECENT FINDINGS: In an attempt to optimize
      clinical research in pneumonia, at the University of Louisville, we developed a
      clinical research coordinating center (CRCC). The center manages clinical studies
      in the field of respiratory infections, with the primary focus being pneumonia.
      Other activities of the CRCC include the organization of an annual clinical
      research training course for physicians and other healthcare workers, and the
      facilitation of international research mentoring by a process of connecting new
      pneumonia investigators with established clinical investigators. SUMMARY: To
      improve clinical research in pneumonia, institutions need to have the appropriate
      infrastructure in place to support investigators in all aspects of the clinical
      research process.

PMID- 29470253
TI  - Management of nontuberculous mycobacterial pulmonary disease.
AB  - PURPOSE OF REVIEW: To highlight recent original research and specialty society
      guidelines regarding the diagnosis and treatment of nontuberculous mycobacterial
      (NTM) pulmonary disease. RECENT FINDINGS: The prevalence of NTM pulmonary disease
      has risen in recent years. The prevalence of individual NTM species varies
      geographically, although Mycobacterium avium complex (MAC) and Mycobacterium
      abscessus complex (MABC) remain among the most commonly encountered in many
      regions. Diagnosis and treatment of NTM pulmonary disease can be complex but
      guideline-based recommendations have been published. However, adherence to
      guideline recommendations is poor. Drug susceptibility testing plays a role with
      important caveats for treatment. Alternative therapies are being explored with
      older antimycobacterial drugs like clofazimine, which has demonstrated efficacy
      and tolerability for treatment-refractory NTM infections, and a novel formulation
      of amikacin for inhalation which may be better tolerated than parenteral
      administration. Several studies have shown that patients will have recurrences as
      high as 48%, and that these are not solely relapses but many cases are
      reinfections with a new organism. United States and European research registries
      of patients with non-cystic fibrosis bronchiectasis are expected to provide
      needed data on clinical characteristics of patients at risk for NTM pulmonary
      disease. SUMMARY: The evidence base for optimal management of NTM pulmonary
      disease is expanding but notable gaps in the literature remain.

PMID- 29470255
TI  - Clinical implications of oncogenic mutations in pulmonary Langerhans cell
      histiocytosis.
AB  - PURPOSE OF REVIEW: Langerhans cell histiocytosis (LCH) is a neoplasm of dendritic
      cells with a wide clinical spectrum. Localized pulmonary LCH occurs in young
      adults with a history of smoking and can either resolve spontaneously or lead to
      progressive decline in pulmonary function. Young children can also present with
      localized disease - frequently bone or skin - or with multifocal or multisystem
      disease. Clinical outcomes in these patients also vary widely, ranging from
      spontaneous resolution to multiorgan failure and death. This review describes
      recent developments in our understanding of the underlying pathogenesis of LCH
      and how these discoveries and other research are affecting how the disease is
      classified, treated and monitored. RECENT FINDINGS: Somatic mutations resulting
      in activation of the mitogen-activated protein kinase (MAPK) pathway were
      recently identified as a key pathogenetic mechanism in both pediatric and
      pulmonary LCH. SUMMARY: Knowledge of underlying pathogenetic mechanisms of LCH
      transforming how this disease and other histocytic/dendritic disorders are
      classified, treated and monitored.

PMID- 29470256
TI  - Systematic screening in hereditary hemorrhagic telangiectasia: a review.
AB  - PURPOSE OF REVIEW: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal
      dominant inherited disease characterized by telangiectasia and arteriovenous
      malformations (AVMs). To date, five genetic types of HHT and one combined
      juvenile polyposis syndrome and HHT are known. Clinical and genetic screening of
      patients suspected with HHT is recommended to confirm the diagnosis and to
      prevent complications associated with HHT. The aim of this article is to give an
      overview of the evidence and to formulate a recommendation for clinicians
      concerning screening for HHT. RECENT FINDINGS: Complications of HHT such as
      stroke, brain abscess and intracranial hemorrhage are caused by pulmonary and
      cerebral AVMs (CAVMs) and can often be prevented by screening and treatment when
      possible. Screening and treatment of these AVMs will result in an increased life
      expectancy comparable with that of the general population as opposed to
      unscreened and untreated HHT patients. SUMMARY: Screening of HHT patients and
      their first-degree relatives is recommended to prevent severe complications
      including stroke, brain abscess and intracranial hemorrhage.

PMID- 29470257
TI  - Dynamic Patient-Specific Three-Dimensional Simulation of Mitral Repair: Can We
      Practice Mitral Repair Preoperatively?
AB  - OBJECTIVE: Planned mitral repair strategies are generally established from
      preoperative echocardiography; however, specific details of the repair are often
      determined intraoperatively. We propose that three-dimensional printed, patient
      specific, dynamic mitral valve models may help surgeons plan and trial all the
      details of a specific patient's mitral repair preoperatively. METHODS: Using
      preoperative echocardiography, segmentation, modeling software, and three
      dimensional printing, we created dynamic, high-fidelity, patient-specific mitral
      valve models including the subvalvular apparatus. We assessed the accuracy of 10
      patient mitral valve models anatomically and functionally in a heart phantom
      simulator, both objectively by blinded echocardiographic assessment, and
      subjectively by two mitral repair experts. After this, we attempted model mitral
      repair and compared the outcomes with postoperative echocardiography. RESULTS:
      Model measurements were accurate when compared with patients on anterior
      posterior diameter, circumference, and anterior leaflet length; however, less
      accurate on posterior leaflet length. On subjective assessment, Likert scores
      were high at 3.8 +/- 0.4 and 3.4 +/- 0.7, suggesting good fidelity of the dynamic
      model echocardiogram and functional model in the phantom to the preoperative
      three-dimensional echocardiogram, respectively. Mitral repair was successful in
      all 10 models with significant reduction in mitral insufficiency. In two models,
      mitral repair was performed twice, using two different surgical techniques to
      assess which provided a better outcome. When compared with the actual patient
      mitral repair outcome, the repaired models compared favorably. CONCLUSIONS:
      Complex mitral valve modeling seems to predict an individual patient's mitral
      anatomy well, before surgery. Further investigation is required to determine
      whether deliberate preoperative practice can improve mitral repair outcomes.

PMID- 29470258
TI  - Improving Quality of Dynamic Airway Computed Tomography Using an Expiratory
      Airflow Indicator Device.
AB  - PURPOSE: Dynamic computed tomography (CT) of the airways is increasingly used to
      evaluate patients with suspected expiratory central airway collapse, but current
      protocols are susceptible to inadequate exhalation caused by variable patient
      compliance with breathing instructions during the expiratory phase. We developed
      and tested a low-cost single-use expiratory airflow indicator device that was
      designed to improve study quality by providing a visual indicator to both patient
      and operator when adequate expiratory flow was attained. MATERIALS AND METHODS: A
      total of 56 patients undergoing dynamic airway CT were evaluated, 35 of whom were
      scanned before introduction of the indicator device (control group), with the
      rest comprising the intervention group. Lung volumes and tracheal cross-sectional
      areas on inspiratory/expiratory phases were computed using automated lung
      segmentation and quantitative software analysis. Inadequate exhalation was
      defined as absolute volume change of <500 mL during the expiratory phase.
      RESULTS: Fewer patients in the intervention group demonstrated inadequate
      exhalation. The average change in volume was higher in the intervention group
      (P=0.004), whereas the average minimum tracheal cross-sectional area was lower
      (P=0.01). CONCLUSIONS: The described expiratory airflow indicator device can be
      used to ensure adequate exhalation during the expiratory phase of dynamic airway
      CT. A higher frequency of adequate exhalation may improve reliability and
      sensitivity of dynamic airway CT for diagnosis of expiratory central airway
      collapse.

PMID- 29470259
TI  - Pure-Tone Audiometry With Forward Pressure Level Calibration Leads to Clinically
      Relevant Improvements in Test-Retest Reliability.
AB  - OBJECTIVES: Clinical pure-tone audiometry is conducted using stimuli delivered
      through supra-aural headphones or insert earphones. The stimuli are calibrated in
      an acoustic (average ear) coupler. Deviations in individual-ear acoustics from
      the coupler acoustics affect test validity, and variations in probe insertion and
      headphone placement affect both test validity and test-retest reliability. Using
      an insert earphone designed for otoacoustic emission testing, which contains a
      microphone and loudspeaker, an individualized in-the-ear calibration can be
      calculated from the ear-canal sound pressure measured at the microphone. However,
      the total sound pressure level (SPL) measured at the microphone may be affected
      by standing-wave nulls at higher frequencies, producing errors in stimulus level
      of up to 20 dB. An alternative is to calibrate using the forward pressure level
      (FPL) component, which is derived from the total SPL using a wideband acoustic
      immittance measurement, and represents the pressure wave incident on the eardrum.
      The objective of this study is to establish test-retest reliability for FPL
      calibration of pure-tone audiometry stimuli, compared with in-the-ear and coupler
      sound pressure calibrations. DESIGN: The authors compared standard audiometry
      using a modern clinical audiometer with TDH-39P supra-aural headphones calibrated
      in a coupler to a prototype audiometer with an ER10C earphone calibrated three
      ways: (1) in-the-ear using the total SPL at the microphone, (2) in-the-ear using
      the FPL at the microphone, and (3) in a coupler (all three are derived from the
      same measurement). The test procedure was similar to that commonly used in
      hearing-conservation programs, using pulsed-tone test frequencies at 0.5, 1, 2,
      3, 4, 6, and 8 kHz, and an automated modified Hughson-Westlake audiometric
      procedure. Fifteen adult human participants with normal to mildly-impaired
      hearing were selected, and one ear from each was tested. Participants completed
      10 audiograms on each system, with test-order randomly varied and with headphones
      and earphones refitted by the tester between tests. RESULTS: Fourteen of 15 ears
      had standing-wave nulls present between 4 and 8 kHz. The mean intrasubject SD at
      6 and 8 kHz was lowest for the FPL calibration, and was comparable with the low
      frequency reliability across calibration methods. This decrease in variability
      translates to statistically-derived significant threshold shift criteria
      indicating that 15 dB shifts in hearing can be reliably detected at 6 and 8 kHz
      using FPL-calibrated ER10C earphones, compared with 20 to 25 dB shifts using
      standard TDH-39P headphones with a coupler calibration. CONCLUSIONS: These
      results indicate that reliability is better with insert earphones, especially
      with in-the-ear FPL calibration, compared with a standard clinical audiometer
      with supra-aural headphones. However, in-the-ear SPL calibration should not be
      used due to its sensitivity to standing waves. The improvement in reliability is
      clinically meaningful, potentially allowing hearing-conservation programs to more
      confidently determine significant threshold shifts at 6 kHz-a key frequency for
      the early detection of noise-induced hearing loss.

PMID- 29470260
TI  - Cavernous Transformation and Granulomatous Epididymis in Behcet Disease.

PMID- 29470261
TI  - Concomitant Parvimonas micra Septic Arthritis and Pseudogout After Total Knee
      Arthroplasty.

PMID- 29470263
TI  - Successful Treatment of Amyloid A-Type Amyloidosis Due to Behcet Disease With
      Tocilizumab.

PMID- 29470262
TI  - Serum S100 Proteins as a Marker of Disease Activity in Large Vessel Vasculitis.

PMID- 29470265
TI  - Standardized Clinical Protocols to Promote Maternal Safety.

PMID- 29470264
TI  - Why Is My Foot Swollen?

PMID- 29470266
TI  - Posterior Reversible Encephalopathy Syndrome.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a newly defined syndrome;
      therefore, this transient clinical condition is not well known and probably
      underdiagnosed. It develops quickly with symptoms that are usually
      indistinguishable from eclampsia. Nurses need to be knowledgeable and aware of
      identifying symptoms and appropriate treatment. The condition is thought to share
      pathophysiology with eclampsia, and it is suggested that endothelial dysfunction
      combined with hypertension causes disruption in the blood brain barrier resulting
      in cerebral edema. Seizures develop secondary to cerebral edema, and mark later
      stages of the disease. Treatment is aimed at reducing blood pressure (BP) with
      antihypertensive therapy and seizure control with magnesium sulfate. When PRES is
      treated early, symptoms typically disappear within a few days and imaging studies
      normalize in several weeks. Permanent brain damage can occur if diagnosis and
      treatment are delayed. If PRES is suspected, thorough focused assessments and
      increased communication among the healthcare team are essential for patient care.
      When pregnant or postpartum women present with elevated BP accompanied with
      neurologic symptoms, imaging studies should be considered. An exemplar case is
      presented of a woman with normal prenatal course that is complicated by rapidly
      developing preeclampsia, eclampsia, and PRES.

PMID- 29470267
TI  - Pregnancy after Solid Organ Transplantation.
AB  - PURPOSE: To explore the reproductive decision-making process with women who were
      organ transplant recipients (renal, lung, & heart transplants). STUDY DESIGN AND
      METHODS: Grounded theory guided data collection and analyses. Mixed methods with
      audiotaped telephone interviews and a written survey measuring social support
      were used. As social support is critical for women who are organ transplant
      recipients considering pregnancy, a search for disconfirming evidence for social
      support via a survey and interviews was included. ANALYSES: Verbatim responses
      were analyzed through the constant comparative method using open, axial, and
      selective coding. Trustworthiness was established through prolonged engagement,
      member checking, and thick descriptions. RESULTS: Participants included 10 women
      who were solid organ recipients (2 lung, 1 heart, and 7 renal transplant
      recipients). The core theme was Wanting a child. Other themes included Getting
      information, Advocating, Dealing with problems, Preparing, Talking, Supporting,
      Coping, and Advising others. There was no evidence of a lack of social support as
      evaluated via the survey or interviews. CLINICAL IMPLICATIONS: This study
      provides new knowledge on clinical decision-making about pregnancy for women who
      are solid organ recipients and for healthcare professionals. Nurses can use these
      data to help guide women on how to obtain the most accurate information to make a
      personal decision about pregnancy and to develop support from their healthcare
      team and family.

PMID- 29470269
TI  - Tattoos and Piercings: Increasingly Accepted but Still Risky.

PMID- 29470268
TI  - Facilitating Early Breast Milk Expression in Mothers of Very Low Birth Weight
      Infants.
AB  - BACKGROUND: Although early initiation of human milk (HM) expression after birth
      is known to increase lactation success in mothers of very low birthweight (VLBW)
      infants, initiation is frequently delayed, potentially decreasing both short- and
      long-term HM production. Obstetrical (OB) nurses are typically the healthcare
      provider responsible for facilitating the initial HM expression session. As
      delays in initiation are common, it is likely that nurses experience obstacles to
      facilitation of an early initiation of HM expression. The purpose of this study
      was to determine barriers OB nurses perceive in facilitating early initiation of
      HM expression in mothers of VLBW infants. STUDY DESIGN AND METHODS: An online
      survey was administered to nurses from three tertiary care OB units in Florida to
      determine perceived barriers to early initiation of HM expression in mothers of
      VLBW infants. RESULTS: Eighty-three nurses completed the survey. The following
      barriers were identified: (1) lack of time and personnel to assist mothers with
      HM expression, (2) nurse's perception of the mother's acuity level, and (3)
      nurse's perception of maternal pain and stress. Discrepancies between nursing
      judgment, action, and knowledge of unit policies were evident. CLINICAL
      IMPLICATIONS: Obstetric nurses encounter barriers when facilitating early HM
      expression in mothers giving birth to VLBW infants. It is possible these barriers
      could be removed through improvements in education, use of innovative staffing
      strategies, and maintenance of evidence-based policies.

PMID- 29470270
TI  - Travel Considerations for Breastfeeding.

PMID- 29470271
TI  - Midwives for Haiti.

PMID- 29470274
TI  - Neonatal Neuroprotection: Bringing Best Practice to the Bedside in the NICU.

PMID- 29470273
TI  - Update on Evaluation, Prevention, and Management of Postpartum Hemorrhage.

PMID- 29470275
TI  - Posterior Reversible Encephalopathy Syndrome.

PMID- 29470276
TI  - Anatomical Feasibility of Extradural Transferring S2 and S3 Ventral Roots to S1
      Ventral Root for Restoring Neurogenic Bladder in Spinal Cord Injury.
AB  - STUDY DESIGN: Anatomic study in six formalin-fixed cadavers. OBJECTIVE: To
      determine the anatomical feasibility of transferring the S2 and S3 ventral roots
      (VRs) to S1 VR as a method for restoring bladder dysfunction in spinal cord
      injury. SUMMARY OF BACKGROUND DATA: A large quantity of researches of
      neuroanastomosis methods have been used for treating the bladder dysfunction in
      spinal cord injury. However, some limitations retard the development of those
      studies. METHODS: In this study, six formalin-fixed cadavers (four males, two
      females) were dissected. The feasibility of exposing the S1, S2, and S3
      extradural nerve roots by the limited laminectomy, isolating the VR and dorsal
      roots from each extradural nerve root and transferring the S2,S3 VRs to the S1 VR
      were assessed. The pertinent distances and the nerve cross-sectional areas in
      each specimen were measured. The morphology of each nerve root was observed by
      hematoxylin-eosin staining. RESULTS: The limited laminectomy was performed to
      expose the S1 to S3 extradural nerve roots. The VRs could be isolated from each
      extradural nerve root at the location of the dorsal root ganglion and the
      hematoxylin-eosin staining showed that there were some connective tissues
      separating the VRs from the corresponding dorsal root ganglion. The S2 and S3 VRs
      have sufficient lengths to be transferred to S1 VR without grafting. The mean
      cross-sectional area of the S1 VR was 2.60 +/- 0.17 mm, and that was 1.02 +/-
      0.32 mm and 0.51 +/- 0.21 mm of the S2 and S3 VRs, respectively. CONCLUSION: This
      study demonstrated that use of the S2 and S3 VRs for extradural transfer to S1 VR
      for restoring bladder dysfunction is surgically feasible. LEVEL OF EVIDENCE: 5.

PMID- 29470277
TI  - Does Duration of Pain at Baseline Influence Clinical Outcomes of Low Back Pain
      Patients Managed on an Evidence-based Pathway?
AB  - STUDY DESIGN: Longitudinal observational study. OBJECTIVE: To investigate the
      association between the duration of pain at baseline and the clinical outcomes of
      patients with low back pain (LBP) enrolled on the North East of England Regional
      Back Pain and Radicular Pain Pathway (NERBPP). SUMMARY OF BACKGROUND DATA: The
      NERBPP is a clinical pathway based upon National Institute for Health and Care
      Excellence (NICE) guidelines (2009) for LBP of <1-year duration. Recent changes
      to NICE guidelines (2016) advocate the same management for all LBP patients
      regardless of pain duration. METHODS: Patients with LBP referred onto the NERBPP
      by their General Practitioner between May 2015 and January 2017 were included.
      Data from 667 patients, who provided pre- and post data for pain (Numerical
      rating scale), function (Oswestry Disability Index), quality-of-life (EuroQol
      five-dimension, five-level questionnaire), anxiety (the Generalized Anxiety
      Disorder Screener), and depression (the Patient Health Questionnaire), were
      analyzed using a series of covariate-adjusted models. Patients were categorized
      into four groups based upon baseline pain duration: <3 months, >=3 to <6 months,
      >=6 months to <12 months, >=12 months. RESULTS: Each group showed improved
      outcomes greater than the minimal clinically important difference (MCID) for each
      measure as defined in NICE guidelines (2016). There was a trend toward better
      outcomes for those with shorter pain durations. The magnitude of the differences
      between the groups, in most instances, was below the MCID. For example, mean
      improvement in function for those with baseline pain duration <3 months was 20
      points and 12 points for those of pain duration >=12 months, both above the MCID
      of >=10. CONCLUSION: Patients with different durations of LBP at baseline
      improved on the NERBPP, supporting the recent modification to NICE guidelines.
      However, those with shorter durations of pain may have superior outcomes in the
      short term, suggesting added benefit in getting patients onto the pathway in the
      early stages of LBP. LEVEL OF EVIDENCE: 3.

PMID- 29470278
TI  - Pullout Strength of Pedicle Screws Following Redirection After Lateral or Medial
      Wall Breach.
AB  - STUDY DESIGN: A cadaveric biomechanical study designed to test the pullout
      strength of pedicle screws. OBJECTIVE: To evaluate the pullout strength of
      redirected pedicle screws with a larger diameter following lateral wall breach,
      redirected pedicle screws of the same diameter following medial wall breach, and
      redirected pedicle screws with a larger diameter following medial wall breach.
      SUMMARY OF BACKGROUND DATA: Screw malposition is one of the main pitfalls of
      inserting pedicle screws. Intraoperatively a malpositioned screw is redirected
      and inserted along the correct axis. METHODS: Forty-seven vertebrae (T9-L5) were
      harvested from eight fresh cadaveric spines. The 18 pedicle screws that breached
      the lateral wall were then removed and redirected using a pedicle screw of 1 mm
      larger in diameter. The 16 pedicle screws that had breached the medial wall were
      then removed and redirected using a pedicle screw of the same diameter. The other
      13 pedicle screws that had breached the medial wall were then removed and
      redirected using a pedicle screw of 1 mm larger in diameter. The pullout strength
      was measured. RESULTS: Following lateral wall breach, mean pullout strength for
      the larger redirected screws was 46.9% greater than that of the correctly aligned
      screws. Following medial wall breach, mean pullout strength for the redirected
      screws of the same diameter was 20.6% less than that of the correctly aligned
      screws. Mean pullout strength for the larger pedicle screws following medial wall
      breach was 27.3% more than that of the correctly aligned screws. CONCLUSION:
      Redirected pedicle screws of larger diameter after a lateral or medial pedicle
      breach show recovery of pullout strength. However, the pullout strength of
      redirected pedicle screws of the same diameter after a medial pedicle breach is
      significantly less than that of correctly aligned screws. LEVEL OF EVIDENCE: 1.

PMID- 29470279
TI  - Acute Serum Cartilage Biomarker Response after Walking and Drop Landing.
AB  - INTRODUCTION: An in-depth understanding of the healthy cartilage response to
      activities of daily living is needed to better understand the complex
      relationship between cartilage health and loading. The purpose was to assess the
      role of loading on the acute serum cartilage oligomeric matrix protein (COMP)
      response in recreationally active individuals. METHODS: Forty individuals without
      previous lower extremity injury participated in this repeated-measures study in
      which each participant completed all conditions during independent data
      collection sessions separated by at least 1 wk. An antecubital blood draw was
      performed before and after walking, drop-landing, and control (i.e., sitting)
      conditions. Commercially available enzyme-linked immunosorbent assays measured
      COMP concentration. The acute COMP response was quantified as the percent change
      of COMP concentration from before to after each condition. A one-way, repeated
      measures ANOVA compared the acute COMP response between conditions. Post hoc
      Pearson product-moment correlation and chi-square analysis determined the
      relationship between the walking and drop-landing acute COMP response within
      individuals. RESULTS: Acute COMP response was greater after walking (+4.2, P =
      0.008) and drop landing (+4.6%, P = 0.002) compared with control (-2.3%), but did
      not differ between the walking and drop-landing conditions (P = 0.596). The
      magnitudes of the acute COMP response during walking and drop landing were
      correlated (r = 0.56, P < 0.001). However, the direction (i.e., either increase
      or decrease) of COMP was not the same after the walking and drop-landing
      conditions (chi1 = 0.870, P = 0.351). CONCLUSIONS: Walking and drop landing
      produced a greater acute COMP response when compared with a control condition in
      healthy individuals, but the acute COMP response was similar between the two
      physical activity conditions, although the conditions differed in magnitude and
      frequency of loading.

PMID- 29470280
TI  - Blood Pressure Response during Cardiopulmonary Exercise Testing in Heart Failure.
AB  - INTRODUCTION: The prognostic value of peak VO2 and VE/VCO2 slope measured during
      cardiopulmonary exercise (CPX) testing has been well established in patients with
      advanced heart failure, but blood pressure response to exercise is less well
      characterized. METHODS: We retrospectively studied 151 outpatients who underwent
      CPX testing as part of an advanced heart failure evaluation. The outcome of
      interest was failure of medical management, defined by death, cardiac
      transplantation, or left ventricular assist device placement. Patients were
      stratified into tertiles by change in systolic blood pressure (SBP) (<13, 13-26,
      and >=27 mm Hg) during exercise. RESULTS: Patients in the lowest tertile had the
      lowest peak VO2 (10.2 vs 10.6 vs 13.6 mL.kg.min, P = <0.001), the highest VE/VCO2
      slope (42.8 vs 42.1 vs 36.3, P = 0.030), the shortest mean exercise time (5.1 vs
      6.0 vs 7.0 min, P = <0.001), and the highest probability of failure of medical
      management at 1.5 yr (0.69 vs 0.41 vs 0.34, P = 0.011). After multivariate
      adjustment, increased SBP <20 mm Hg during exercise was associated with a lower
      hazard of medical management failure (hazard ratio = 0.96, 95% confidence
      interval [CI] = 0.934-0.987), whereas SBP increases >20 mm Hg were associated
      with an increased hazard (hazard ratio = 1.046, 95% CI = 1.018-1.075).
      CONCLUSION: In conclusion, changes in SBP during CPX testing provide additional
      prognostic information above standard clinical variables. The peculiar increase
      in risk noted in those with a rise in SBP >20 mm Hg is less clear and needs to be
      investigated further.

PMID- 29470281
TI  - Vascular Nitric Oxide-Superoxide Balance and Thrombus Formation after Acute
      Exercise.
AB  - INTRODUCTION: An acute bout of strenuous exercise in humans results in transient
      impairment of nitric oxide (NO)-dependent function, but it remains unknown
      whether this phenomenon is associated with increased risk of thrombotic events
      after exercise. This study aimed to evaluate effects of a single bout of
      exhaustive running in mice on the balance of vascular NO/reactive oxygen species
      production, and on thrombogenicity. METHODS: At different time points (0, 2, and
      4 h) after exercise and in sedentary C57BL/6 mice, the production of NO and
      superoxide (O2) in aorta was measured by electron paramagnetic resonance spin
      trapping and by dihydroethidium/high-performance liquid chromatography-based
      method, respectively, whereas collagen-induced thrombus formation was analyzed in
      a microchip-based flow-chamber system (total thrombus-formation analysis system).
      We also measured pre- and postexercise plasma concentration of nitrite/nitrate
      and 6-keto-PGF1alpha. RESULTS: An acute bout of exhaustive running in mice
      resulted in decreased production of NO and increased production of O2 in aorta,
      with maximum changes 2 h after completion of exercise when compared with
      sedentary mice. However, platelet thrombus formation was not changed by exercise
      as evidenced by unaltered time to start of thrombus formation, capillary
      occlusion time, and total thrombogenicity (area under the flow pressure curve) as
      measured in a flow-chamber system. Strenuous exercise increased the plasma
      concentration of nitrite but did not affect nitrate and 6-keto-PGF1alpha
      concentrations. CONCLUSION: An acute bout of strenuous exercise in mice reduced
      NO and in parallel increased O2 production in aorta. This response was most
      pronounced 2 h after exercise. Surprisingly, the reduced NO and increased O2
      production in mice after exercise did not result in increased platelet-dependent
      thrombogenicity. These results show that transient reduction in NO
      bioavailability does not modify thromboresistance in healthy mice after exercise.

PMID- 29470282
TI  - The 2017 Shwachman Award.

PMID- 29470283
TI  - 2017 AAP Murray Davidson Award.

PMID- 29470284
TI  - Evolving Practice and Changing Phenotype in Pediatric Autoimmune Liver Disease:
      Outcomes From an Australian Center.
AB  - OBJECTIVES: Autoimmune liver disease (AILD) incorporates primary sclerosing
      cholangitis (PSC), autoimmune hepatitis (AIH), and autoimmune sclerosing
      cholangitis (ASC). ASC is a condition that includes overlap of AIH and PSC. We
      investigate changes in practice in relation to diagnosis and phenotype over 2
      time periods. METHODS: Retrospective chart review was conducted from January 2000
      to 2016. Data were divided into two 8-year cohorts, CI and C2. RESULTS: Data were
      collected in 75 children, 29 in 2000-2007 (C1) and 46 in 2008-2016 (C2).
      Presenting AILD type was AIH in 59%, ASC in 10%, and PSC in 31%. Final AILD type
      was AIH in 53%, ASC in 16%, and PSC in 31%. When comparing C1 to C2, those with
      AIH decreased (65% vs 45%) and those with ASC increased (14% vs 18%). Use of
      magnetic resonance cholangio-pancreatography increased from 34% in C1 to 65% in
      C2. Advanced liver disease on biopsy was noted in 53% of all children at
      presentation. Only 5 female children progressed to liver transplant (3 ASC-IBD
      [inflammatory bowel disease]; 1 PSC-IBD; 1 AIH). Colonoscopy performance
      increased from 48% in C1 to 63% in C2 with diagnosis of AILD-IBD increasing from
      31% to 52%. Right-sided disease was present in 46% and macroscopic rectal sparing
      in 36% of those with ulcerative colitis (UC). Colectomy was required in 3
      children with large duct PSC-IBD. CONCLUSIONS: PSC and ASC are increasing in
      relevance along with IBD and reflect increasing performance of magnetic resonance
      cholangio-pancreatography and colonoscopy. Large duct PSC and ASC with IBD are
      risk factors for colectomy and along with female gender, for liver transplant.

PMID- 29470285
TI  - Clinical and Imaging Predictors of Surgical Splenorenal Shunt Dysfunction in
      Pediatric Patients.
AB  - PURPOSE: Few established criteria exist to prompt angiographic evaluation and
      intervention for surgically created splenorenal shunts (SRS). Clinical and
      Doppler ultrasound (DUS) imaging predictors of shunt dysfunction were evaluated
      in this retrospective study. MATERIALS AND METHODS: Consecutive patients
      undergoing SRS angiography over a 10-year period were retrospectively identified.
      Preangiography platelet count and DUS measurements of spleen diameter, maximum
      splenic vein velocity, and maximum shunt velocity were assessed and compared to
      findings at subsequent catheter angiography. RESULTS: Twenty-six SRS angiograms
      were performed in 16 patients. Two of the 26 procedures were excluded from
      analysis due to insufficient baseline preangiography clinical and DUS data. In
      the remaining 24 cases, significant stenosis/occlusion was confirmed at
      angiography in 20, whereas wide patency was seen in 4. For the 20 cases of
      angiographically confirmed significant stenosis/occlusion, when compared to
      baseline post-SRS creation to immediate preangiography evaluation there was a
      greater decrease in platelet count (-51.8% vs -19.4%), a greater increase in
      spleen diameter (+13.4% vs +3.7%), a greater increase in maximum shunt velocity
      (+74.7% vs +59.7%), and a greater decrease in splenic vein velocity (-25.0% vs 
      18.5%). CONCLUSION: Clinical evidence of splenic sequestration and DUS finding of
      increased maximum shunt velocity correlate with angiographic findings of SRS
      dysfunction and could be used to help predict the need for shunt intervention.

PMID- 29470287
TI  - 2017 NASPGHAN Distinguished Service Award.

PMID- 29470286
TI  - Genetic Variants Associated With Obesity and Insulin Resistance in Hispanic Boys
      With Nonalcoholic Fatty Liver Disease.
AB  - BACKGROUND AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD)
      disproportionately affects Hispanic boys. Further, obesity and insulin resistance
      are major risk factors for NAFLD. No gene localization studies had been performed
      on children with biopsy-proven NAFLD. This study aims to identify genomic
      variants associated with increased adiposity and insulin resistance in a
      population of children with varying histologic severity of NAFLD. METHODS: We
      conducted a genome-wide association scan (GWAS) including 624,297 single
      nucleotide polymorphisms (SNPs) distributed among all 22 autosomal chromosomes in
      234 Hispanic boys (up to 18 years of age) who were consecutively recruited in a
      prospective cohort study in the Nonalcoholic Steatohepatitis Clinical Research
      Network Studies. Traits were examined quantitatively using linear regression.
      SNPs with P value <10 and a minor allele frequency >5% were considered
      potentially significant. RESULTS: Evaluated subjects had a median age of 12.0
      years, body mass index (BMI) of 31.4, and hemoglobin A1C (Hgb A1C) of 5.3. The
      prevalence of NAFL, borderline NASH, and definite NASH were 23%, 53%, and 22%,
      respectively. The GWAS identified 10 SNPs that were associated with BMI z score,
      6 within chromosome 2, and 1 within CAMK1D, which has a potential role in liver
      gluconeogenesis. In addition, the GWAS identified 9 novel variants associated
      with insulin resistance: HOMA-IR (6) and HbA1c (3). CONCLUSIONS: This study of
      Hispanic boys with biopsy-proven NAFLD with increased risk for the metabolic
      syndrome revealed novel genetic variants that are associated with obesity and
      insulin resistance.

PMID- 29470288
TI  - Digested Early Preterm Human Milk Suppresses Tumor Necrosis Factor-induced
      Inflammation and Cytotoxicity in Intestinal Epithelial Cells.
AB  - OBJECTIVES: The aim of this study was to determine the effect of digested whole
      human milk (HM; first sample available after birth from mothers of premature
      infants) on inflammation, oxidative stress, and cytotoxicity in Caco-2 human
      intestinal epithelial cells stimulated with lipopolysaccharides or tumor necrosis
      factor (TNF) to mimic the potential in vivo insults facing the premature infant's
      gastrointestinal tract. METHODS: Fully differentiated Caco-2 cells were exposed
      to digested HM (n = 10; samples from 10 different individuals) before stimulation
      with lipopolysaccharides, TNF, or no stimulation overnight. Inflammation was
      determined by production of interleukin-8, oxidative stress by levels of F2
      isoprostane, and cytotoxicity by released lactate dehydrogenase. RESULTS: HM
      significantly suppressed interleukin-8 production and cytotoxicity in TNF
      stimulated cells, while also suppressing cell death under baseline conditions.
      Individual HM samples differed widely in their ability to modulate cellular
      responses. CONCLUSIONS: Results from this study provide evidence that digested HM
      can reduce both an exaggerated inflammatory response and intestinal damage that
      contribute to the pathogenesis of necrotizing enterocolitis.

PMID- 29470289
TI  - Endoscopic Management Postcholedochoduodenostomy for Choledochal Cysts.

PMID- 29470290
TI  - Autoimmune Hepatitis in Children and Adolescents: Effect on Quality of Life.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of autoimmune
      hepatitis (AIH) on the quality of life of children and adolescents and to
      identify which variables effect health-related quality of life (HRQoL). METHODS:
      The Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) was used to evaluate
      HRQoL. In addition, a questionnaire was applied which included signs, symptoms,
      and use of medications. RESULTS: A total of 43 patients (mean age, 15.0 +/- 3.9
      years; 65.1% girls; 90.7% with type 1 AIH) was evaluated. Advanced liver disease
      was present in 30.2%, and 18.6% had sclerosing cholangitis. Treatment was
      effective in 93.1% of patients. The lowest HRQoL scores were associated with the
      school (67.7), emotional (68.2), and psychosocial (75.5) domains. Compared with
      healthy children, patients presented lower scores on the total, psychosocial,
      emotional, and school domains (P < 0.05). The presence of symptoms (beta = 0.39,
      P < 0.01), extrahepatic autoimmune diseases (beta = 0.27, P < 0.05), and a
      dislike of taking medication (beta = 0.40, P < 0.01) negatively affected the
      psychosocial PedsQL 4.0 score, and the presence of symptoms (beta = 0.40, P <
      0.01) negatively affected the total PedsQL 4.0 score. CONCLUSIONS: AIH has a
      significant and negative effect on HRQoL among children and adolescents. The
      presence of symptoms, extrahepatic autoimmune diseases, and a dislike of taking
      medication were associated with the worsening of HRQoL. Providers should work
      with professionals trained to improve QoL to help improve treatment adherence and
      disease outcomes.

PMID- 29470291
TI  - Recurrent Abdominal Pain in Children: Summary Evidence From 3 Systematic Reviews
      of Treatment Effectiveness.
AB  - OBJECTIVES: Between 4% and 25% of school-aged children complain of recurrent
      abdominal pain (RAP) severe enough to interfere with their daily activities.
      METHODS: We carried out a systematic review of randomised controlled trials
      (RCTs) in eleven databases and 2 trials registries from inception to June 2016.
      An update search was run in November 2017. All screening was performed by 2
      independent reviewers. Included studies were appraised using the Cochrane risk of
      bias tool and the evidence assessed using GRADE. We included any dietary,
      pharmacological or psychosocial intervention for RAP, defined by Apley or an
      abdominal pain-related functional gastrointestinal disorder, as defined by the
      Rome III criteria, in children and adolescents. RESULTS: We included 55 RCTs,
      involving 3572 children with RAP (21 dietary, 15 pharmacological, 19
      psychosocial, and 1 multiarm). We found probiotic diets, cognitive-behavioural
      therapy (CBT) and hypnotherapy were reported to reduce pain in the short-term and
      there is some evidence of medium term effectiveness. There was insufficient
      evidence of effectiveness for all other dietary interventions and psychosocial
      therapies. There was no robust evidence of effectiveness for pharmacological
      interventions. CONCLUSIONS: Overall the evidence base for treatment decisions is
      poor. These data suggest that probiotics, CBT, and hypnotherapy could be
      considered as part of holistic management of children with RAP. The evidence
      regarding relative effectiveness of different strains of probiotics is currently
      insufficient to guide clinical practice. The lack of evidence of effectiveness
      for any drug suggests that there is little justification for their use outside of
      well-conducted clinical trials. There is an urgent need for high-quality RCTs to
      provide evidence to guide management of this common condition.

PMID- 29470292
TI  - Rectal Picking Masquerading as Inflammatory Bowel Disease in Prader-Willi
      Syndrome.
AB  - Prader-Willi syndrome (PWS) is a genetic syndrome in which individuals have
      multisystem medical challenges. Gastroenterological difficulties in the syndrome
      include decreased vomiting, constipation, delayed gastric emptying, delayed
      colonic transit, dysphagia, increased choking, and increased risk of gastric
      dilation and rupture. In addition, self-injurious behavior such as rectal picking
      may be present and severe enough to lead to rectal ulceration and bleeding. Many
      patients have extensive gastroenterological workup and treatment before their
      ultimate diagnosis of severe rectal picking. We describe 4 new cases of rectal
      picking in individuals with PWS leading to rectal bleeding and ulceration as well
      as a review of the literature of prior cases of severe rectal picking in PWS and
      potential treatment options. It is important to recognize these cases early in
      order to prevent unnecessary treatments and implement appropriate behavioral
      interventions.

PMID- 29470293
TI  - Medium-term Outcome of Laparoscopic Kasai Portoenterostomy for Biliary Atresia
      With 49 Cases.
AB  - OBJECTIVE: The aim of this study was to evaluate the mid-term results of
      laparoscopic Kasai portoenterostomy (LKPE) for biliary atresia (BA) at our
      hospital. METHODS: From May 2009 to May 2012, the charts of infants with BA who
      underwent LKPE were reviewed retrospectively. The clearance of jaundice (CJ) as
      well as 3-year, and 5-year survival with native liver (SNL) rates were analyzed
      and compared with those after open Kasai portoenterostomy (OKPE). RESULTS: Forty
      nine patients with BA who underwent LKPE were assigned to group A, and 40
      patients with BA who underwent OKPE were assigned to group B. All patients in
      both groups had type III non-syndromic BA, and the LKPE and OKPE procedures were
      performed by 2 different surgical teams at our hospital. After median follow-up
      periods of 77 months in group A and 79 months in group B, the CJ and 3- and 5
      year SNL rates were 61.2%, 55.1%, and 36.7% in group A, and 45.0%, 37.5%, and
      25.0% in group B, respectively. The difference of CJ between group A and group B
      was not significant. The Kaplan-Meier method analysis showed that the difference
      in SNL between group A and group B was not significant either. CONCLUSIONS: LKPE
      for patients with BA was a technically feasible and alternative procedure to
      OKPE. The 3- and 5-year SNL rates after LKPE were not different compared to those
      after OKPE.

PMID- 29470294
TI  - Dilation of Esophageal Stricture in a Pediatric Patient Using Functional Lumen
      Imaging Probe Technology Without the Use of Fluoroscopy.

PMID- 29470295
TI  - An Omental Lymphatic Malformation Mimicking Ascites in a 2-Year-Old Boy.

PMID- 29470296
TI  - Plexiform Fibromyxoma: A Rare Benign Gastric Tumor.

PMID- 29470297
TI  - Competitively Selected Donor Fecal Microbiota Transplantation: Butyrate
      Concentration and Diversity as Measures of Donor Quality.
AB  - In this prospective cohort study, we examine the feasibility of a protocol to
      optimize microbiota for fecal microbiota transplantation (FMT). Donor stool
      metrics generally accepted as markers of gut health were used to select a stool
      donor based on superior microbial diversity, balanced constitution of
      Bacteroidetes versus Firmicutes and high concentration of fecal butyrate.
      Selected donor microbiota was then administered via FMT. A total of 10 patients
      with median age of 12 years with recurrent Clostridium difficile infection
      received the intervention. The rate of recurrence-free resolution with 1-2 FMTs
      was 100% at Week 10. With a single FMT, 80% of patients cleared Clostridium
      difficile infection without recurrence, whereas 20% of patients required a single
      re-treatment. No serious adverse events occurred. Microbiota sequencing revealed
      that recipients' gut microbiota phylogenic diversity increased by 72-hours post
      transplantation, with sustainment over 10-week follow-up. This study highlights
      the feasibility of purposefully selecting the most ideal microbiota for
      transplantation.

PMID- 29470298
TI  - CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH RETINAL PIGMENT EPITHELIAL TEAR
      IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
AB  - PURPOSE: To report a patient presenting a retinal pigment epithelial tear in
      which optical coherence tomography angiography enabled the visualization of
      subfoveal choroidal neovascularization (CNV) not evidenced by the fluorescein
      angiography. She was treated with 3 monthly intravitreous anti-VEGF injections
      and intraretinal fluid resolution occurred. METHODS: Observational case report.
      RESULTS: A 62-year-old Caucasian woman presented with decreased visual acuity in
      the right eye for 3 months. Fundus biomicroscopy revealed a yellowish macular
      lesion associated with intraretinal hemorrhage. Fluorescein angiography showed a
      large hyperfluorescent area consistent with window defect. Optical coherence
      tomography showed a retinal pigment epithelial tear with subretinal fluid.
      However, there was no clear evidence of CNV on fluorescein angiography or OCT.
      Optical coherence tomography angiography confirmed the presence of an active CNV
      by the visualization of the neovascular network in the region corresponding to
      the scrolled up retinal pigment epithelium. CONCLUSION: This case report
      demonstrates that optical coherence tomography angiography can be useful to
      confirm the presence of CNV in cases where fluorescein angiography and OCT cannot
      establish the diagnosis. The reported case suggests the applicability of optical
      coherence tomography angiography in patients in whom retinal pigment epithelial
      tear is detected and associated CNV is suspected.

PMID- 29470299
TI  - CHOROIDAL THICKNESS CHANGES IN A PATIENT DIAGNOSED WITH CENTRAL SEROUS
      CHORIORETINOPATHY DURING FOLLOW-UP FOR PACHYCHOROID PIGMENT EPITHELIOPATHY.
AB  - PURPOSE: To evaluate chronological changes in choroidal thickness in a patient
      with pachychoroid pigment epitheliopathy (PPE) who was later diagnosed with
      central serous chorioretinopathy (CSC) during follow-up. METHODS: Case report.
      RESULTS: A 43-year-old man complained of metamorphopsia in the left eye.
      Funduscopy showed several punctate white subretinal lesions at the macula, but no
      macular serous retinal detachment in the left eye. Retinal pigment epithelium
      abnormality without serous retinal detachment at the macula on optical coherence
      tomography and choroidal vascular hyperpermeability on indocyanine green
      angiography suggested PPE in the left eye. Macular lesions disappeared with no
      treatment. Twenty-five months after the initial visit, PPE recurred in the left
      eye. Thirty-five months after the initial visit, the patient was diagnosed with
      CSC in the left eye. Macular serous retinal detachment spontaneously resolved. In
      the eye with PPE and CSC, the choroid was consistently thicker than that in the
      fellow eye during follow-up. The choroid became thicker during the alternate
      onsets of PPE and CSC and thinner after regression of these diseases. CONCLUSION:
      These results suggest that PPE and CSC overlap clinically and choroidal
      thickening is involved in the pathogenesis of both diseases.

PMID- 29470300
TI  - RETINOCYTOMA WITH VITREOUS SEEDING: NEW INSIGHTS FROM ENHANCED DEPTH IMAGING
      OPTICAL COHERENCE TOMOGRAPHY AND HIGH-RESOLUTION POSTERIOR SEGMENT
      ULTRASONOGRAPHY.
AB  - PURPOSE: To report an atypical case of a patient with symptomatic retinocytoma
      associated with diffuse calcified vitreous seeds. METHODS: Retrospective chart
      review. RESULTS: A 46-year-old healthy woman presented with a history of floaters
      in the right eye for several months. She had been referred for abnormal findings
      in the retina and vitreous on routine examination. Visual acuity was 20/20. An
      incidental retinocytoma associated with extensive calcified vitreous seeding was
      observed. Enhanced depth optical coherence tomography showed an absence of normal
      retinal layers with numerous cystoid cavities throughout the lesion. High
      resolution 20-MHz posterior B-scan ultrasonography demonstrated that the
      calcified vitreous seeds emanated from the peaked portion of the retinal tumor.
      CONCLUSION: Calcified vitreous seeding is a rare finding associated with
      retinocytomas. Enhanced depth imaging optical coherence tomography and high
      resolution B-scan ultrasonography may be useful tools in the diagnosis of this
      uncommon retinal tumor.

PMID- 29470301
TI  - A CASE OF INTRARETINAL PERIPAPILLARY NEOVASCULARIZATION IN ABCA4-RELATED
      RETINOPATHY.
AB  - PURPOSE: To report a case of ABCA4-related retinopathy and potential
      complications. METHODS: The authors describe a case report of intraretinal
      neovascularization in a patient with ABCA4-related retinopathy and describe the
      multimodal retinal imaging findings. RESULTS: A 49-year-old woman presents with
      cystoid macular edema and diffuse intraretinal and perivascular hyperpigmentation
      in both eyes. Genetic testing confirmed ABCA4-related retinopathy. Fluorescein
      angiography revealed peripapillary intraretinal neovascularization in the absence
      of any other identifiable retinal pathology. CONCLUSION: To the authors'
      knowledge, this is the first reported case of intraretinal neovascularization
      associated ABCA4-related retinopathy. Ancillary testing of ABCA4-related
      retinopathy with fluorescein angiography or optical coherence tomography
      angiography may be helpful in identifying this rare complication.

PMID- 29470302
TI  - HYDRATION FOLDS IN RHEGMATOGENOUS RETINAL DETACHMENT.
AB  - PURPOSE: To describe two cases of retinal detachment with hydration folds and
      discuss the possible cause of these outer retinal abnormalities. METHODS: The
      medical and imaging records of two patients with retinal detachment and hydration
      folds were examined. PATIENTS: A 43-year-old myopic woman who developed a retinal
      detachment secondary to a macular hole and a 35-year-old man referred with a
      rhegmatogenous retinal detachment masquerading as an exudative detachment were
      each found to have retinal hydration folds. RESULTS: On near-infrared reflectance
      imaging, the hydration folds appeared similar to eddy currents, and these
      corresponded to curvilinear outer retinal plications on optical coherence
      tomography. The photoreceptor outer segments appeared thickened and elongated,
      and there was apparent lateral expansion of the outer retinal layers. CONCLUSION:
      Hydration folds are found in rhegmatogenous retinal detachment and demonstrate
      reproducible imaging characteristics on near-infrared imaging and optical
      coherence tomography. The cause for such outer retinal plications is currently
      unknown. We suspect that they form as a result of hydration of the
      glycosaminoglycans in the interphotoreceptor matrix, which lies between the
      photoreceptors. Additional studies are warranted to explore this pathophysiology.

PMID- 29470303
TI  - Clues in Histopathological Diagnosis of Panniculitis.
AB  - BACKGROUND: Panniculitides comprise a group of heterogeneous inflammatory
      diseases. Nevertheless, histopathological study along with clinicopathological
      correlation usually led to a specific diagnosis. In most textbooks, the first
      step in the diagnosis is to classify them as mostly septal or lobular depending
      on where the inflammatory infiltrate is located. The second step is deciding if
      vasculitis is present or not. Finally, the third step is further characterizing
      the inflammatory infiltrate. However, in addition to the algorithmic approach to
      panniculitis diagnosis, some subtle changes may help to the diagnosis. OBJECTIVE:
      To review some clues in panniculitis dermatopathological diagnosis such as
      presence of granulation tissue, sclerotic connective tissue septa, small
      granulomas arranged around a central clear space, so-called ghost adipocytes,
      needle-shaped crystals, small lobules with a proliferation of capillaries,
      Splendore-Hoeppli phenomenon, refractile microspheres, neutrophilic infiltrates,
      granulomas and fibroplasia or presence of adipose tissue in dermis. METHODS: We
      have compiled 12 clues based in our personal experience in this field.
      LIMITATIONS: Specificity and sensibility of every clue may vary and these clues
      are a guide to correct diagnoses that should rely in clinicopathological
      correlation. CONCLUSION: Knowledge of these 12 clues will help to increase the
      diagnostic accuracy in panniculitis diagnosis.

PMID- 29470304
TI  - Index Case of Cutaneous Follicular Mycosis Fungoides With Central Nervous System
      Involvement and Review of Literature.
AB  - Central nervous system involvement by mycosis fungoides (MF) is rare and is
      usually seen in advanced stages of the disease. We describe a patient with early
      stage follicular MF who presented with changes in mental status. Despite an
      initial diagnosis of vasculitis based on clinical and brain biopsy results, the
      postmortem examination revealed extensive infiltration of MF cells throughout the
      brain with leptomeningeal involvement. This case in addition to the accompanied
      review of literature illustrates the importance of the awareness of central
      nervous system involvement by MF and highlights the need for an urgent neurologic
      evaluation in patients with a history of MF now presenting with neurologic signs
      or symptoms.

PMID- 29470305
TI  - Annular Scaly Plaque on the Left Foot: Answer.

PMID- 29470306
TI  - Pruriginous Lesions in a Young Girl: Answer.

PMID- 29470307
TI  - Annular Scaly Plaque on the Left Foot: Challenge.

PMID- 29470308
TI  - EFFICACY AND SAFETY OUTCOMES OF INTRAVITREAL AFLIBERCEPT FOCUSING ON PATIENTS
      WITH DIABETIC MACULAR EDEMA FROM JAPAN.
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal aflibercept
      injection (IAI) in Japanese patients with diabetic macular edema (DME). METHODS:
      VIVID-DME was a Phase 3 study comprising patients with DME randomized 1:1:1 to
      IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 4 weeks until Week 16 then 8-week
      dosing (2q8), and laser. A total of 403 patients (76 Japanese) were included in
      this study. VIVID-Japan (72; all Japanese patients) was a nonrandomized, open
      label study comprising Japanese patients with DME receiving IAI 2q4 until Week
      16, then 2q8. Primary efficacy endpoint (Week 52) of VIVID-DME was mean change
      from baseline in best-corrected visual acuity; VIVID-Japan evaluated safety and
      tolerability. RESULTS: Mean change in best-corrected visual acuity (letters) for
      2q4, 2q8, and laser groups was +10.6, +10.9, and +1.2 and +9.8, +9.5, and +1.1 in
      the non-Japanese and Japanese populations of VIVID-DME, respectively. In VIVID
      Japan, it was +9.3 for IAI 2q8. Intravitreal aflibercept injection also provided
      consistently greater benefits for anatomical outcomes versus laser. Adverse
      events were consistent with the known safety profile of IAI. CONCLUSION: In
      Japanese patients with DME, IAI treatment was superior to laser for visual and
      anatomical outcomes and resulted in efficacy and safety outcomes similar to those
      in a non-Japanese 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.

PMID- 29470309
TI  - Comet Lesions in Retinitis Pigmentosa.

PMID- 29470310
TI  - Novel Vicryl Releasable Suture Technique to Close Leaking Sclerotomies in a
      Transconjunctival Vitrectomy.

PMID- 29470311
TI  - ROUTINE FUNDUS SCREENING OF FAMILIES OF CHILDREN WITH RETINOBLASTOMA: A
      Prospective Study of 131 Consecutive Families.
AB  - PURPOSE: To discuss the importance of routine ophthalmic examination of parents
      and siblings of retinoblastoma (RB) patients. METHODS: Prospective nonrandomized
      observational/interventional case series of consecutive families of 131 RB
      patients. RESULTS: Routine ophthalmic examination of families (parents and
      siblings) of 131 consecutive newly diagnosed RB patients, including 262 parents
      and 23 siblings, revealed spontaneously regressed RB in at least 1 parent of 10
      (8%) patients and active RB in at least 1 sibling of 3 (2%) patients. Of the 10
      parents with spontaneously regressed RB, the lesions were unilateral (n = 7) or
      bilateral (n = 3). The regression patterns (n = 13) were comparable with
      postirradiation regression patterns Type 1 (n = 3), Type 2 (n = 2), Type 3 (n =
      2), and Type 4 (n = 3), and spontaneous phthisis bulbi (n = 3). Fundus screening
      of siblings revealed active RB in at least 1 sibling of 3 (2%) patients. Of these
      3 siblings, 2 had unilateral and 1 had bilateral disease. The mean age at
      detection of RB was 15 months (median, 6 months; range, 2-36 months). The disease
      was unilateral in 2 and bilateral in 1 patient. Based on International
      Classification of Intraocular Retinoblastoma, the tumors (n = 4) were classified
      as Group A (n = 2) and Group B (n = 2). CONCLUSION: Routine fundus screening of
      siblings allows for early detection of RB in otherwise asymptomatic children.
      Detection of spontaneously regressed RB in parents may act as a surrogate marker
      for germline RB1 mutation and is helpful in genetic counseling.

PMID- 29470312
TI  - Heterozygous mutations in GTP-cyclohydrolase-1 reduce BH4 biosynthesis but not
      pain sensitivity.
AB  - Human studies have demonstrated a correlation between noncoding polymorphisms of
      "the pain protective" haplotype in the GCH1 gene that encodes for GTP
      cyclohydrolase I (GTPCH1)-which leads to reduced tetrahydrobiopterin (BH4)
      production in cell systems-and a diminished perception of experimental and
      clinical pain. Here, we investigate whether heterozygous mutations in the GCH1
      gene which lead to a profound BH4 reduction in patients with dopa-responsive
      dystonia (DRD) have any effect on pain sensitivity. The study includes an
      investigation of GCH1-associated biomarkers and pain sensitivity in a cohort of
      22 patients with DRD and 36 controls. The patients with DRD had, when compared
      with controls, significantly reduced levels of BH4, neopterin, biopterin, and
      GTPCH1 in their urine, blood, or cytokine-stimulated fibroblasts, but their pain
      response with respect to non-painful stimulation, (acute) stimulus-evoked pain,
      or pain response after capsaicin-induced sensitization was not significantly
      different. A family-specific cohort of 11 patients with DRD and 11 controls were
      included in this study. The patients with DRD were heterozygous for the pain
      protective haplotype in cis with the GCH1 disease-causing mutation, c.899T>C. No
      effect on pain perception was observed for this combined haplotype. In
      conclusion, a reduced concentration of BH4 is not sufficient to alter ongoing
      pain sensitivity or evoked pain responses.

PMID- 29470313
TI  - Injustice perceptions about pain: parent-child discordance is associated with
      worse functional outcomes.
AB  - Pain is experienced within and influenced by social environments. For children
      with chronic pain, the child-parent relationship and parental beliefs about pain
      are particularly important and may influence pain outcomes. Pain-related
      injustice perceptions have recently been identified as an important cognitive
      emotional factor for children with pain. The current study aimed to better
      understand the pain-related injustice perceptions of children with chronic pain
      and their parents. The sample consisted of 253 pediatric chronic pain patients
      (mean age = 14.1 years, 74% female) presenting to a tertiary pain clinic.
      Patients completed measures of pain intensity, pain-related injustice
      perceptions, stress, functional disability, and quality of life. Parents
      completed a measure of pain-related injustice perceptions about their child's
      pain. Child-parent dyads were categorized into 1 of 4 categories based on the
      degree of concordance or discordance between their scores on the injustice
      measures. One-way analysis of variances examined differences in pain intensity,
      stress, functional disability, and quality of life across the 4 dyad categories.
      Our findings indicated that both the degree (concordant vs discordant) and
      direction (discordant low child-high parent vs discordant high child-low parent)
      of similarity between child and parent injustice perceptions were associated with
      child-reported pain intensity, stress, functional disability, and quality of
      life. The poorest outcomes were reported when children considered their pain as
      highly unjust, but their parents did not. These findings highlight the important
      role of parents in the context of pain-related injustice perceptions in pediatric
      chronic pain.

PMID- 29470315
TI  - A Global Presence.

PMID- 29470314
TI  - Genetic variation in P2RX7 and pain tolerance.
AB  - P2X7 is a nonselective cation channel activated by extracellular ATP. P2X7
      activation contributes to the proinflammatory response to injury or bacterial
      invasion and mediates apoptosis. Recently, P2X7 function has been linked to
      chronic inflammatory and neuropathic pain. P2X7 may contribute to pain modulation
      both by effects on peripheral tissue injury underlying clinical pain states, and
      through alterations in central nervous system processing, as suggested by animal
      models. To further test its role in pain sensitivity, we examined whether
      variation within the P2RX7 gene, which encodes the P2X7 receptor, was associated
      with experimentally induced pain in human patients. Experimental pain was
      assessed in Tromso 6, a longitudinal and cross-sectional population-based study
      (N = 3016), and the BrePainGen cohort, consisting of patients who underwent
      breast cancer surgery (N = 831). For both cohorts, experimental pain intensity
      and tolerance were assessed with the cold-pressor test. In addition, multisite
      chronic pain was assessed in Tromso 6 and pain intensity 1 week after surgery was
      assessed in BrePainGen. We tested whether the single-nucleotide polymorphism
      rs7958311, previously implicated in clinical pain, was associated with
      experimental and clinical pain phenotypes. In addition, we examined effects of
      single-nucleotide polymorphisms rs208294 and rs208296, for which previous results
      have been equivocal. Rs7958311 was associated with experimental pain intensity in
      the meta-analysis of both cohorts. Significant associations were also found for
      multisite pain and postoperative pain. Our results strengthen the existing
      evidence and suggest that P2X7 and genetic variation in the P2RX7-gene may be
      involved in the modulation of human pain sensitivity.

PMID- 29470316
TI  - Protecting the Brain With Xenon Anesthesia for Neurosurgical Procedures.
AB  - Xenon possesses some, but not all, of the clinical features of an ideal
      anesthetic agent. Besides well-known advantages of rapid awakening, stable
      hemodynamics and lack of biotransformation, preclinical data lead to the
      expectation of xenon's advantageous use for settings of acute ongoing brain
      injury; a single randomized clinical trial using an imaging biomarker for
      assessing brain injury corroborated xenon's preclinical efficacy in protecting
      the brain from further injury. In this review, we discuss the mechanisms and
      hence the putative applications of xenon for brain protection in neurosurgery.
      Although the expense of this rare monoatomic gas will likely prevent its
      widespread penetration into routine clinical neurosurgical practice, we draw
      attention to the theoretical benefits of xenon anesthesia over other anesthetic
      regimens for awake craniotomy and for neurosurgery in older, high-risk, and
      sicker patients.

PMID- 29470317
TI  - The Effects of Leukocyte Filtration on Cell Salvaged Autologous Blood Transfusion
      on Lung Function and Lung Inflammatory and Oxidative Stress Reactions in Elderly
      Patients Undergoing Lumbar Spinal Surgery.
AB  - BACKGROUND: This study was designed to investigate the effects of leukocyte
      filtration of autologous salvaged blood on lung function, lung inflammatory
      reaction, and oxidative stress reaction in elderly patients undergoing lumbar
      spinal surgery. MATERIALS AND METHODS: Sixty elderly patients undergoing lumbar
      spinal surgery were randomly divided into 2 groups: Leukocyte Filter group and
      Control group. Serum levels of inflammatory markers including white blood cell
      and polymorphonuclear count, neutrophil elastase, serum surfactant protein A,
      methane dicarboxylic aldehyde, superoxide dismutase, interleukin (IL)-6, IL-8,
      tumor necrosis factor-alpha, and respiratory function markers including dynamic
      respiratory system compliance, oxygenation index, and respiratory index were
      measured immediately before induction of anesthesia (T0), immediately before
      blood transfusion (T1), and 1 (T2), 6 (T3), and 12 hours (T4) after end of blood
      transfusion. RESULTS: The Leukocyte Filter group had higher dynamic respiratory
      system compliance at T2, oxygenation index at T2 and T3, respiratory index and
      superoxide dismutase at T2, T3, and T4 than those in the Control group (P<0.05).
      The Leukocyte Filter group had lower white blood cell, polymorphonuclear count,
      neutrophil elastase, serum surfactant protein A, methane dicarboxylic aldehyde,
      IL-6, IL-8, and tumor necrosis factor-alpha at T2, T3, and T4 than those in the
      Control group (P<0.05). There were no significant differences in adverse
      reactions related specifically to blood transfusion or postoperative respiratory
      complications within 72 hours. CONCLUSIONS: Salvaged autologous blood leukocyte
      filtration can improve ventilation, promote gas exchange and oxygenation, and
      inhibit lung inflammatory and oxidative stress reactions in elderly patients
      undergoing lumbar spinal surgery.

PMID- 29470319
TI  - Splenic Rupture in Children With Portal Hypertension.
AB  - INTRODUCTION: Massive splenomegaly from portal hypertension (PHTN) in children
      raises the specter of splenic rupture; however, the incidence, etiology, and risk
      of rupture have not been studied, nor have existing practices to reduce risk. We
      therefore performed an international survey to describe the splenic rupture cases
      in PHTN and to describe the existing empirical practice among hepatologists.
      METHODS: A questionnaire was constructed to elicit cases of splenic rupture and
      collect hepatologists' common practices for prevention of splenic rupture.
      Pediatric hepatologists working in selected tertiary academic centers in the
      United States, Canada, and the United Kingdom were contacted. RESULTS:
      Hepatologists from 30 of 35 centers who met the inclusion criteria replied to the
      survey. Thirteen cases of splenic rupture were described of which 11 resulted
      from trauma. In the opinion of the practitioners, high-risk activities were
      football, hockey, and wrestling. Sixty-one percent recommended total restriction
      from high-risk activities. Seventy-four percent stated that platelet count had no
      effect on this decision and 61% advised a spleen guard for certain activities.
      CONCLUSIONS: Splenic rupture in patients with PHTN and splenomegaly seems to be
      rare. The reported splenic rupture cases were mostly related to falling (and not
      to participation in sports). There was general agreement among hepatologists
      about restricting high impact sports. There was variation in recommendations
      regarding the use of a spleen guard. The authors recommend use of spleen guards
      in children with splenomegaly from PHTN for physical activities with risk of fall
      or blunt abdominal trauma.

PMID- 29470320
TI  - Exchangeable Zinc Pool Size at Birth in Pakistani Small for Gestational Age and
      Appropriate for Gestational Age Infants Do Not Differ But Are Lower Than in US
      Infants.
AB  - OBJECTIVES: Small for gestational age (SGA) infants are more susceptible to
      infectious morbidity and growth faltering compared to their appropriate for
      gestational age (AGA) counterparts. Zinc supplementation of SGA infants may be
      beneficial but the underlying susceptibility to zinc deficiency of SGA infants
      has not been examined. METHODS: In a community-based, observational, longitudinal
      study in a peri-urban settlement of Karachi, Pakistan, we compared the size of
      the exchangeable zinc pools (EZPs) in term SGA and AGA infants at birth and at 6
      months of age, hypothesizing that the EZP would be lower in the SGA group. To
      measure EZP size, a zinc stable isotope was intravenously administered within 48
      hours of birth (n = 17 and 22) at 6 months (n = 11 and 14) in SGA and AGA
      infants, respectively. Isotopic enrichment in urine was used to determine EZP.
      RESULTS: No significant difference was detected in the mean (+/-standard
      deviation) EZP between SGA and AGA infants at birth, with values of 9.8 +/- 3.5
      and 10.1 +/- 4.1 mg/kg, respectively (P = 0.86), or at 6 months. Longitudinal EZP
      measurements demonstrated a significant decline in EZP relative to body weight in
      both groups at 6 months (P < 0.001). Mean EZP (adjusted for body weight) size at
      birth for the combined Pakistani groups was significantly lower than AGA infants
      at birth in the United States (P = 0.017). CONCLUSIONS: These results did not
      support a difference in zinc endowment between SGA and AGA Pakistani infants.
      They, however, do suggest lower in utero zinc transfer to the fetus in a setting
      where poor maternal nutritional status may confer a high susceptibility to
      postnatal zinc deficiency.

PMID- 29470321
TI  - Long-term Exposure of Children to a Mixed Lipid Emulsion Is Less Hepatotoxic Than
      Soybean-based Lipid Emulsion.
AB  - Lipid emulsions have been associated with liver injury. Newer mixed emulsions
      (ML), such as SMOFlipid (Fresenius Kabi, Germany), are thought to be more
      hepatoprotective than soybean-based emulsions (SL), such as Intralipid (Baxter).
      Pediatric studies comparing long-term use between the 2 are limited. This study
      compares the severity of hepatic injury between a prospective cohort of
      hospitalized children on ML (n = 20) and a historical age- and diagnosis-matched
      cohort of hospitalized children on SL (n = 20). Median exposure to ML and SL were
      10 versus 6 weeks (P = 0.030), respectively, at similar median lipid doses (2.2
      vs 2.1 g . kg . day). Using a generalized estimating equations approach,
      conjugated bilirubin trajectory was found to be lower in patients on ML compared
      with SL (P < 0.001), suggesting that prolonged exposure (>=4 weeks) to ML is
      associated with decreased liver injury compared with SL in hospitalized children.

PMID- 29470323
TI  - Biliary-enteric Fistula, A Rare Complication of Peptic Ulcer Disease in Children.

PMID- 29470325
TI  - Mass Screening for Celiac Disease Among School-aged Children: Toward Exploring
      Celiac Iceberg in Saudi Arabia: Erratum.

PMID- 29470324
TI  - Response to Letter: How Much Free Sugars Intake Should Be Recommended for
      Children Younger Than 2 Years Old?

PMID- 29470326
TI  - National Partnership for Maternal Safety: Consensus Bundle on Safe Reduction of
      Primary Cesarean Births-Supporting Intended Vaginal Births.
AB  - Cesarean births and associated morbidity and mortality have reached near epidemic
      proportions. The National Partnership for Maternal Safety under the guidance of
      the Council on Patient Safety in Women's Health Care responded by developing a
      patient safety bundle to reduce the number of primary cesarean births. Safety
      bundles outline critical practices to implement in every maternity unit. This
      National Partnership for Maternity Safety bundle, as with other bundles, is
      organized into four domains: Readiness, Recognition and Prevention, Response, and
      Reporting and Systems Learning. Bundle components may be adapted to individual
      facilities, but standardization within an institution is advised. Evidence-based
      resources and recommendations are provided to assist implementation.

PMID- 29470327
TI  - A Medically Supervised Pregnancy Exercise Intervention in Obese Women: A
      Randomized Controlled Trial.

PMID- 29470328
TI  - In Reply.

PMID- 29470329
TI  - Maternal Pulse Pressure and the Risk of Postepidural Complications: A Randomized
      Controlled Trial.

PMID- 29470330
TI  - In Reply.

PMID- 29470331
TI  - Prediction Is Very Difficult, Especially If It Is About the Future.

PMID- 29470333
TI  - Practice Bulletin No. 141: Management of Menopausal Symptoms: Correction.

PMID- 29470332
TI  - In Reply.

PMID- 29470334
TI  - Maternal Pulse Pressure and the Risk of Postepidural Complications: A Randomized
      Controlled Trial: Correction.

PMID- 29470322
TI  - Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint
      Recommendations of the North American Society for Pediatric Gastroenterology,
      Hepatology, and Nutrition and the European Society for Pediatric
      Gastroenterology, Hepatology, and Nutrition.
AB  - This document serves as an update of the North American Society for Pediatric
      Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society
      for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2009 clinical
      guidelines for the diagnosis and management of gastroesophageal reflux disease
      (GERD) in infants and children and is intended to be applied in daily practice
      and as a basis for clinical trials. Eight clinical questions addressing
      diagnostic, therapeutic and prognostic topics were formulated. A systematic
      literature search was performed from October 1, 2008 (if the question was
      addressed by 2009 guidelines) or from inception to June 1, 2015 using Embase,
      MEDLINE, the Cochrane Database of Systematic Reviews and the Cochrane Central
      Register of Controlled Clinical Trials. The approach of the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) was applied to
      define and prioritize outcomes. For therapeutic questions, the quality of
      evidence was also assessed using GRADE. Grading the quality of evidence for other
      questions was performed according to the Quality Assessment of Studies of
      Diagnostic Accuracy (QUADAS) and Quality in Prognostic Studies (QUIPS) tools.
      During a 3-day consensus meeting, all recommendations were discussed and
      finalized. In cases where no randomized controlled trials (RCT; therapeutic
      questions) or diagnostic accuracy studies were available to support the
      recommendations, expert opinion was used. The group members voted on each
      recommendation, using the nominal voting technique. With this approach,
      recommendations regarding evaluation and management of infants and children with
      GERD to standardize and improve quality of care were formulated. Additionally, 2
      algorithms were developed, 1 for infants <12 months of age and the other for
      older infants and children.

PMID- 29470337
TI  - ACOG Publications.

PMID- 29470338
TI  - ACOG Practice Bulletin No. 192 Summary: Management of Alloimmunization During
      Pregnancy.
AB  - When any fetal blood group factor inherited from the father is not possessed by
      the mother, antepartum or intrapartum fetal-maternal bleeding may stimulate an
      immune reaction in the mother. Maternal immune reactions also can occur from
      blood product transfusion. The formation of maternal antibodies, or
      "alloimmunization," may lead to various degrees of transplacental passage of
      these antibodies into the fetal circulation. Depending on the degree of
      antigenicity and the amount and type of antibodies involved, this transplacental
      passage may lead to hemolytic disease in the fetus and neonate. Undiagnosed and
      untreated, alloimmunization can lead to significant perinatal morbidity and
      mortality. Advances in Doppler ultrasonography have led to the development of
      noninvasive methods of management of alloimmunization in pregnant women. Together
      with more established protocols, Doppler ultrasound evaluation may allow for a
      more thorough and less invasive workup with fewer risks to the mother and fetus.
      Prevention of alloimmunization is addressed in another Practice Bulletin ().

PMID- 29470339
TI  - ACOG Practice Bulletin No. 193 Summary: Tubal Ectopic Pregnancy.
AB  - Ectopic pregnancy is defined as a pregnancy that occurs outside of the uterine
      cavity. The most common site of ectopic pregnancy is the fallopian tube. Most
      cases of tubal ectopic pregnancy that are detected early can be treated
      successfully either with minimally invasive surgery or with medical management
      using methotrexate. However, tubal ectopic pregnancy in an unstable patient is a
      medical emergency that requires prompt surgical intervention. The purpose of this
      document is to review information on the current understanding of tubal ectopic
      pregnancy and to provide guidelines for timely diagnosis and management that are
      consistent with the best available scientific evidence.

PMID- 29470340
TI  - ACOG Committee Opinion No. 731 Summary: Group Prenatal Care.
AB  - Individual prenatal care is intended to prevent poor perinatal outcomes and
      provide education to women throughout pregnancy, childbirth, and the postpartum
      period through a series of one-on-one encounters between a woman and her
      obstetrician or other obstetric care provider. Concerns regarding increasing
      health care costs, health care provider availability, dissatisfaction with wait
      times, and the minimal opportunity for education and support associated with the
      individual care model have given rise to interest in alternative models of
      prenatal care. One alternative model, group prenatal care, may be beneficial or
      preferred for some practice settings and patient populations, although individual
      prenatal care remains standard practice. Group prenatal care models are designed
      to improve patient education and include opportunities for social support while
      maintaining the risk screening and physical assessment of individual prenatal
      care. Bringing patients with similar needs together for health care encounters
      increases the time available for the educational component of the encounter,
      improves efficiency, and reduces repetition. Evidence suggests patients have
      better prenatal knowledge, feel more ready for labor and delivery, are more
      satisfied with care in prenatal care groups, and initiate breastfeeding more
      often. There is no evidence that suggests that group prenatal care causes harm.
      Individual and group care models warrant additional study with a goal of
      demonstrating differences in outcomes and identifying populations that benefit
      most from specific care models.

PMID- 29470341
TI  - Clinical Updates in Women's Health Care Summary: Arthritis.
AB  - Arthritis is a commonly encountered problem in daily clinical practice, and with
      an aging population it will be as prevalent as any other chronic illness, such as
      diabetes mellitus, hypertension, and hypercholesterolemia. Obstetrician
      gynecologists often encounter patients with arthritic symptoms in their
      practices. They may find it challenging to identify the underlying cause of
      arthritis and provide recommendations, as well as provide obstetric care to
      patients with known arthritis. The monograph will discuss common forms of
      arthritis, diagnostic testing and appropriate management, and referral of
      patients who need specialized care. Commonly encountered forms of inflammatory
      arthritis are discussed in this monograph with special emphasis on diagnosis and
      management. Management of arthritis in the context of pregnancy and lactation
      also is discussed.

PMID- 29470342
TI  - ACOG Practice Bulletin No. 192: Management of Alloimmunization During Pregnancy.
AB  - When any fetal blood group factor inherited from the father is not possessed by
      the mother, antepartum or intrapartum fetal-maternal bleeding may stimulate an
      immune reaction in the mother. Maternal immune reactions also can occur from
      blood product transfusion. The formation of maternal antibodies, or
      "alloimmunization," may lead to various degrees of transplacental passage of
      these antibodies into the fetal circulation. Depending on the degree of
      antigenicity and the amount and type of antibodies involved, this transplacental
      passage may lead to hemolytic disease in the fetus and neonate. Undiagnosed and
      untreated, alloimmunization can lead to significant perinatal morbidity and
      mortality. Advances in Doppler ultrasonography have led to the development of
      noninvasive methods of management of alloimmunization in pregnant women. Together
      with more established protocols, Doppler ultrasound evaluation may allow for a
      more thorough and less invasive workup with fewer risks to the mother and fetus.
      Prevention of alloimmunization is addressed in another Practice Bulletin ().

PMID- 29470343
TI  - ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy.
AB  - Ectopic pregnancy is defined as a pregnancy that occurs outside of the uterine
      cavity. The most common site of ectopic pregnancy is the fallopian tube. Most
      cases of tubal ectopic pregnancy that are detected early can be treated
      successfully either with minimally invasive surgery or with medical management
      using methotrexate. However, tubal ectopic pregnancy in an unstable patient is a
      medical emergency that requires prompt surgical intervention. The purpose of this
      document is to review information on the current understanding of tubal ectopic
      pregnancy and to provide guidelines for timely diagnosis and management that are
      consistent with the best available scientific evidence.

PMID- 29470344
TI  - ACOG Committee Opinion No. 731: Group Prenatal Care.
AB  - Individual prenatal care is intended to prevent poor perinatal outcomes and
      provide education to women throughout pregnancy, childbirth, and the postpartum
      period through a series of one-on-one encounters between a woman and her
      obstetrician or other obstetric care provider. Concerns regarding increasing
      health care costs, health care provider availability, dissatisfaction with wait
      times, and the minimal opportunity for education and support associated with the
      individual care model have given rise to interest in alternative models of
      prenatal care. One alternative model, group prenatal care, may be beneficial or
      preferred for some practice settings and patient populations, although individual
      prenatal care remains standard practice. Group prenatal care models are designed
      to improve patient education and include opportunities for social support while
      maintaining the risk screening and physical assessment of individual prenatal
      care. Bringing patients with similar needs together for health care encounters
      increases the time available for the educational component of the encounter,
      improves efficiency, and reduces repetition. Evidence suggests patients have
      better prenatal knowledge, feel more ready for labor and delivery, are more
      satisfied with care in prenatal care groups, and initiate breastfeeding more
      often. There is no evidence that suggests that group prenatal care causes harm.
      Individual and group care models warrant additional study with a goal of
      demonstrating differences in outcomes and identifying populations that benefit
      most from specific care models.

PMID- 29470345
TI  - Summary of 2017 FDA Public Workshop: Antibody-mediated Rejection in Kidney
      Transplantation.
AB  - Despite major advances in understanding the pathophysiology of antibody-mediated
      rejection (AMR); prevention, diagnosis and treatment remain unmet medical needs.
      It appears that early T cell-mediated rejection, de novo donor-specific antibody
      (dnDSA) formation and AMR result from patient or physician initiated suboptimal
      immunosuppression, and represent landmarks in an ongoing process rather than
      separate events. On April 12 and 13, 2017, the Food and Drug Administration
      sponsored a public workshop on AMR in kidney transplantation to discuss new
      advances, importance of immunosuppressive medication nonadherence in dnDSA
      formation, associations between AMR, cellular rejection, changes in glomerular
      filtration rate, and challenges of clinical trial design for the prevention and
      treatment of AMR. Key messages from the workshop are included in this summary.
      Distinction between type 1 (due to preexisting DSA) and type 2 (due to dnDSA)
      phenotypes of AMR needs to be considered in patient management and clinical trial
      design. Standardization and more widespread adoption of routine posttransplant
      DSA monitoring may permit timely diagnosis and understanding of the natural
      course of type 2 and chronic AMR. Clinical trial design, especially as related to
      type 2 and chronic AMR, has specific challenges, including the high prevalence of
      nonadherence in the population at risk, indolent nature of the process until the
      appearance of graft dysfunction, and the absence of accepted surrogate endpoints.
      Other challenges include sample size and study duration, which could be mitigated
      by enrichment strategies.

PMID- 29470346
TI  - Utilisation of declined liver grafts yields comparable transplant outcomes and
      previous decline should not be a deterrent to graft use.
AB  - BACKGROUND: In the United Kingdom, up to 20% of liver graft offers are not
      utilized for transplantation and the reasons for graft refusal are multi
      factorial and not consistent amongst transplant units. METHODS: Liver grafts
      previously declined by other transplant centers in UK but transplanted in our
      unit in Birmingham between 2011 and 2015 were analyzed. According to the
      indicated reason for previous declines, liver grafts were categorized into 3
      refusal groups: "quality", "logistics" and "other reasons". Results were compared
      to a matched, low risk cohort of livers primarily accepted and transplanted at
      our center. RESULTS: During the study period, 206 livers (DBD: n=141 (68.4%);
      DCD: n=65 (31.6%) were transplanted, which were previously discarded by a median
      of 4 other UK centres. The majority of declines were donor quality (n=102; 49.5%)
      refusals followed by logistics (n=45; 21.8%) and other reasons (n=59; 28.6%).
      Transplantation from both graft types (DBD and DCD) and all 3 refusal groups
      achieved equally good outcomes with an overall low complication rate. The
      incidence of primary-non-function (PNF, 2.4%vs.1.7%; p=0.5483), in-hospital
      mortality (6.3%vs.4.1%; p=0.2293) and 3-year graft (82.5% vs. 84.1%; p=0.6872)-
      and patient (85.4%vs.87.6%; p=0.8623) survival was comparable between livers
      previously declined and livers primarily accepted and transplanted at our centre.
      CONCLUSION: Transplantation of declined livers can achieve comparable outcomes to
      primary liver low risk graft offers. Previous refusal should not be taken as a
      barrier to use the graft and with appropriate recipient selection more lives
      could be saved.

PMID- 29470347
TI  - Establishing a Core Outcome Measure for Graft Health: A Standardized Outcomes in
      Nephrology-Kidney Transplantation (SONG-Tx) Consensus Workshop Report.
AB  - BACKGROUND: Graft loss, a critically important outcome for transplant recipients,
      is variably defined and measured, and incompletely reported in trials. We
      convened a consensus workshop on establishing a core outcome measure for graft
      loss for all trials in kidney transplantation. METHODS: Twenty-five kidney
      transplant recipients/caregivers and 33 health professionals from 8 countries
      participated. Transcripts were analyzed thematically. RESULTS: Five themes were
      identified. "Graft loss as a continuum" conceptualizes graft loss as a process,
      but requiring an endpoint defined as a discrete event. In "defining an event with
      precision and accuracy," loss of graft function requiring chronic dialysis
      (minimum, 90 days) provided an objective and practical definition; retransplant
      would capture preemptive transplantation; relisting was readily measured but
      would overestimate graft loss; and allograft nephrectomy was redundant in being
      preceded by dialysis. However, the thresholds for renal replacement therapy
      varied. Conservative management was regarded as too ambiguous and complex to use
      routinely. "Distinguishing death-censored graft loss" would ensure clarity and
      meaningfulness in interpreting results. "Consistent reporting for decision
      making" by specifying time points and metrics (ie time to event) was suggested.
      "Ease of ascertainment and data collection" of the outcome from registries could
      support use of registry data to efficiently extend follow-up of trial
      participants. CONCLUSIONS: A practical and meaningful core outcome measure for
      graft loss may be defined as chronic dialysis or retransplant, and distinguished
      from loss due to death. Consistent reporting of graft loss using standardized
      metrics and time points may improve the contribution of trials to decision making
      in kidney transplantation.

PMID- 29470348
TI  - Predicting Expected Organ Donor Numbers in Australian Hospitals Outside of the
      Donate-Life Network Using the ANZICS Adult Patient Database.
AB  - BACKGROUND: The majority of organ donations in Australia occur in the DonateLife
      Network of hospitals, but limited monitoring at other sites may allow donation
      opportunities to be missed. Our aim was to estimate expected donor numbers using
      routinely collected data from the Australian and New Zealand Intensive Care
      Society Adult Patient Database and determine whether unrecognized potential
      donors might exist in non-DonateLife hospitals. METHODS: All deaths at 150
      Australian intensive care units (ICUs) contributing to the Australian and New
      Zealand Intensive Care Society Adult Patient Database were analyzed between
      January 2010 and December 2015. Donor numbers were extracted from the Australian
      and New Zealand Organ Donor registry. A univariate linear regression model was
      developed to estimate expected donor numbers in DonateLife hospitals, then
      applied to non-DonateLife hospitals. RESULTS: Of 33 614 deaths at 71 DonateLife
      hospitals, 6835 (20%) met criteria as "ICU deaths potentially suitable to be
      donors," and 1992 (6%) were actual donors. There was a consistent relationship
      between these groups (R = 0.626, P < 0.001) allowing the development of a
      prediction model which adequately estimated expected donors. Of 8077 deaths in 79
      non-DonateLife ICUs, 452 (6%) met criteria as potentially suitable donors.
      Applying the prediction model developed in DonateLife hospitals, the estimated
      expected donors in non-DonateLife hospitals was 130. However, there were only 75
      actual donors. CONCLUSIONS: It is possible to estimate the expected number of
      Australian organ donors using routinely collected registry data. These findings
      suggest that there may be a small but significant pool of underutilized potential
      donors in non-DonateLife hospitals. This may provide an opportunity to increase
      donation rates.

PMID- 29470349
TI  - Impaired Secretion of TNF-alpha by Monocytes Stimulated With EBV Peptides
      Associates With Infectious Complications After Kidney Transplantation.
AB  - BACKGROUND: The successful development of immunosuppressive agents has
      paradoxically led to an era in which adverse effects of immunosuppression, such
      as infections and cancer, are now a major concern in solid organ recipients.
      Nevertheless, the main focus of immune monitoring research remains the
      identification of rejection. There is currently no clinical tool to assess the
      net state of immunosuppression or to identify patients at increased risk of
      infectious complications. METHODS: We report a prospective, longitudinal study in
      which we conducted detailed phenotyping of over 300 peripheral blood mononuclear
      cell samples from 45 kidney recipients during the first 24 months posttransplant.
      Patients were classified as cases or controls according to the following events:
      an opportunistic infection, recurring bacterial infections, or de novo neoplasia.
      RESULTS: Using a training cohort, an exploratory analysis revealed that the
      TNFalpha response to synthetic Epstein-Barr virus peptides by CD14CD16 monocytes
      was lower in cases. A classifier rule based on 2 or greater consecutive values
      below a threshold of 73% of TNFalpha-positive cells provided a sensitivity and
      specificity of 83%. In the validation cohort, the assay exhibited a sensitivity
      of 90% and a specificity of 63%. Analysis of IFNgamma responses by T cells showed
      no correlation with the cases' phenotype. The association between
      overimmunosuppression status and the monocyte response was independent of age,
      renal function, and immunosuppressive regimen. CONCLUSIONS: These data suggest
      that patients with infectious complications posttransplantation have lower
      CD14CD16 monocyte responses to Epstein-Barr virus peptides. This assay seems
      promising to help personalize the immunotherapy.

PMID- 29470350
TI  - Analysis of Luminex-based Algorithms to Define Unacceptable HLA Antibodies in CDC
      crossmatch Negative Kidney Transplant Recipients.
AB  - BACKGROUND: HLA-specific antibodies detected by solid phase assays are
      increasingly used to define unacceptable HLA antigen mismatches (UAM) before
      renal transplantation. The accuracy of this approach is unclear. METHODS: Day of
      transplant sera from 211 complement-dependent cytotoxicity crossmatch-negative
      patients were retrospectively analyzed for donor-specific anti-HLA antibodies
      (DSA) using Luminex technology. HLA were defined as UAM if DSA had mean
      fluorescence intensity above (I) 3000 (patients retransplanted and those with DSA
      against HLA class I and II) or 5000 (all other patients), (II) 5000 for HLA-A, 
      B, and -DR and 10 000 for HLA DQ or (III) 10 000 (all HLA). We then studied the
      accuracy of these algorithms to identify patients with antibody-mediated
      rejection (AMR) and graft loss. UAM were also determined in 256 transplant
      candidates and vPRA levels calculated. RESULTS: At transplantation, 67 of 211
      patients had DSA. Of these, 31 (algorithm I), 24 (II) and 17 (III) had UAM. Nine
      (I and II) and 8 (III) of 11 early AMR episodes and 7 (I), 6 (II) and 5 (III) of
      9 graft losses occurred in UAM-positive patients during 4.9 years of follow-up.
      Algorithms I and II identified patients with persistently lower glomerular
      filtration rate even in the absence of overt AMR. Of the waiting list patients,
      22-33% had UAM with median virtual panel reactive antibody of 69.2% to 79.1%.
      CONCLUSIONS: Algorithms I and II had comparable efficacy but were superior to
      Algorithm III in identifying at-risk patients at an acceptable false-positive
      rate. However, Luminex-defined UAM significantly restrict the donor pool of
      affected patients, which might prolong waiting time.

PMID- 29470351
TI  - Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft
      Failure Within the First 3 Months of Liver Transplantation.
AB  - BACKGROUND: Causes of severe cholestasis after liver transplantation (LT) are
      multi-factorial. Although the etiology is predictable in some, others culminate
      in graft/patient loss without a definitive cause identified. Severe cholestasis
      is usually associated with overlapped histological findings of rejection and
      biliary features, and diagnostic interpretation may pose a challenge. METHODS:
      This is 10-year retrospective analysis of patients with unexplained severe
      cholestasis resulting in death/graft loss within 90 days of LT. Of 1 583 LT
      during the study period, 90-day graft failure occurred in 129 (8%) cases; a total
      of 45 (3%) patients had unresolving severe cholestasis (bilirubin, >100 MUmol/L;
      alkaline phosphatase, >400 UI/L after 15 days from LT), excluding those due to
      primary nonfunction/sepsis/vascular causes (n = 84). Demographics, allograft
      biopsies, radiological investigations, and clinical outcome were analyzed.
      RESULTS: All patients had persistent abnormal liver biochemistry. Doppler
      ultrasound scan was normal in all cases. Thirty-five (78%) recipients had at
      least 1 allograft biopsy (2 [1-9]). On the first biopsy, 22 (63%) patients had
      acute rejection, 4 (18%) early-chronic rejection, 12 (34%) antibody-mediated
      rejection. In subsequent biopsies chronic rejection was evident in 5 (14%) cases.
      Donor-specific antibodies were detected in all patients tested. Biliary anatomy
      was studied in detail in 9 (20%) patients, all presenting biliary strictures. The
      majority (n = 39; 87%) died within 32 (10-91) days, only survivors were from
      retransplantation (n = 3;6.5%) and biliary intervention (n = 3;6.5%).
      CONCLUSIONS: Unresolving severe cholestasis after LT is a key parameter
      predicting patient/allograft outcome. Histologically, rejection seems to overlap
      with biliary strictures; hence, allograft biopsy with signs of rejection should
      not be a reason to overlook biliary problems, in particular when biliary features
      are present. Only extensive radiological investigation/intervention or
      retransplantation prevents patient/allograft loss.

PMID- 29470352
TI  - Intraoperative Management of Liver Transplant Patients Without the Routine Use of
      Renal Replacement Therapy.
AB  - BACKGROUND: Renal failure is common among patients undergoing liver
      transplantation. Liver allocation based on the model for end-stage liver disease
      score has increased the number of recipients who require perioperative renal
      replacement therapy (RRT). Although RRT can be continued intraoperatively, the
      risks and benefits of intraoperative RRT are not well defined. The aim of this
      study is to report the intraoperative management of patients with pretransplant
      renal failure at a transplant center with extremely infrequent utilization of
      intraoperative RRT. MATERIALS AND METHODS: We performed a retrospective analysis
      of all adult patients undergoing orthotopic liver or simultaneous liver-kidney
      (SLK) transplantation between June 2009 and December 2015. Patients were divided
      into 2 groups based on their need for pretransplant RRT. RESULTS: A total of 785
      patients underwent liver or SLK transplant during the study period. One hundred
      and seventy-four patients (22.2%) required preoperative dialysis. Only 2 patients
      required intraoperative RRT. There was no difference in the incidence of acidosis
      or hyperkalemia between patients who required preoperative dialysis and those who
      did not. CONCLUSIONS: We describe the successful management of patients
      undergoing liver or SLK transplantation almost entirely without the need for
      intraoperative RRT.

PMID- 29470353
TI  - Clinical Efficacy of Percutaneous Transhepatic Portal Vein Angioplasty for Late
      onset Portal Vein Stenosis in Pediatric Liver Transplant Patients.
AB  - BACKGROUND: Stenosis of the portal vein (PV) is a rare complication after liver
      transplantation (LT) in pediatric patients, and it adversely affects outcomes. We
      reviewed the safety and efficacy of percutaneous transhepatic balloon angioplasty
      (PTBA) as a treatment for post-LT late-onset PV stenosis (PVS). METHODS: Three
      hundred eighteen patients between the ages of 0 and 21 years received an LT from
      2001 to 2016 at this tertiary center. Twenty-one children were evaluated for PVS
      using percutaneous portal venography. RESULTS: Of the 21, 19 patients (7 female,
      12 male) with a median age of 12 years (7-15 years) were diagnosed with PVS and
      received PTBA. Two patients were excluded: one did not have PVS, and one received
      shunt surgery. Median time between LT and PTBA was 83 months (interquartile
      range, 49-138). For patients in whom pressure could be accurately measured (n =
      9), mean PV pressure gradient was 6.3 mm Hg (SD, 5.0) preprocedure and 0.9 mm Hg
      (SD, 1.2) postprocedure. Mean percentage improvement in gradient across the
      stenotic region was 86.2% (SD, 15.9%; P < 0.01). At 12-month postprocedure, there
      was a mean improvement (pre-PTBA vs post-PTBA means) in bilirubin by 28.2% (0.6
      mg/dL vs 0.4 mg/dL, P = 0.07), aspartate aminotransferase by 31.2% (116.3 IU/L vs
      28.1 IU/L, P = 0.04), alanine aminotransferase by 40.7% (140.3 IU/L vs 28.6 IU/L,
      P = 0.07), gamma-glutamyltransferase by 29.0% (337.2 IU/L vs 38.0 IU/L, P = 0.06)
      and platelets by 62.1% (128.3 vs 191.1 * 10/L, P = 0.03). The PV patency was
      successfully maintained in 18 of 19 patients for a median of 16 months
      (interquartile range, 5-35). One patient received a successful repeat procedure
      for restenosis at 6 weeks. CONCLUSION: Angioplasty for PVS after pediatric LT is
      a safe and effective treatment with good patency and improved clinical outcomes.
      Longer follow-up studies are required.

PMID- 29470354
TI  - Poor Survival after Retransplantation in NASH cirrhosis.
AB  - BACKGROUND: Nonalcoholic steatohepatitis (NASH) cirrhosis is a common indication
      for liver transplantation (LT) in the U.S. There is a paucity of data on
      retransplantation (re-LT) in those who were initially transplanted for NASH.
      METHODS: We queried the UNOS data sets from 2002-2016 to analyze the outcomes of
      adults with NASH (n=128) and compared them to groups that received re-LT for
      cryptogenic cirrhosis (CC, n=189), alcoholic cirrhosis (AC, n=300) or autoimmune
      hepatitis cirrhosis (AIH-C, n=118) after excluding multiple-organ re-LT and
      individuals with HCC. We estimated survival probabilities using a Kaplan-Meier
      estimator, and a relative risk of patient and graft mortality using proportional
      hazards regression. RESULTS: The NASH group was older and had a higher prevalence
      of obesity, type II diabetes mellitus, renal insufficiency, portal vein
      thrombosis, and poor performance status. The median interval between 1st and 2nd
      LT was shorter in the NASH group (27 days). The graft and patient 5-year survival
      rates were lower for the NASH group after re-LT compared to the other 3 groups.
      After adjusting for demographic and disease complication factors, the factors
      that increased a risk of patient or graft failure were a poor performance status
      (HR=1.64 [1.19-2.26]), donor risk index (HR= 1.51 [1.08-2.12]) and a high MELD
      score (HR= 1.02 [1.00-1.04]). CONCLUSIONS: Despite the comparable outcomes
      reported for initial LT among the various etiologies, the outcome of re-LT is
      significantly worse for NASH cirrhosis.

PMID- 29470355
TI  - Effects of Warm Versus Cold Ischemic Donor Lung Preservation on the Underlying
      Mechanisms of Injuries During Ischemia and Reperfusion.
AB  - BACKGROUND: Ischemia-reperfusion injury related to lung transplantation is a
      major contributor to early postoperative morbidity and mortality. We hypothesized
      that donation after cardiac death donor lungs experience warm ischemic conditions
      that activate different injurious mechanisms compared with donor lungs that
      undergo prolonged cold ischemic conditions. METHODS: Rat donor lungs were
      preserved under different cold ischemic times (CIT) (12 hours or 18 hours), or
      under warm ischemia time (WIT) (3 hours) after cardiac death, followed by single
      left lung transplantation. Lung function was analyzed during the 2-hour
      reperfusion period. Microscopic injury, cell death, energy status, and
      inflammatory responses were assessed. RESULTS: Pulmonary oxygenation function was
      significantly worse in both 18hCIT and WIT groups, accompanied by higher peak
      airway pressure, acute lung injury scores, and expression of cell death markers
      compared with the 12hCIT control group. In lung tissue, reperfusion induced
      increased expression levels of interleukin (IL)-1alpha, IL-1beta, IL-6, and
      chemokines CCL2, CCL3, CXCL1, and CXCL2 in CIT lungs. Notably, these changes were
      much lower in the WIT group. Additionally, plasma levels of IL-6, IL-18, CCL2,
      and vascular endothelial growth factor were significantly higher, and adenosine
      triphosphate levels were significantly reduced in warm versus cold ischemic
      lungs. CONCLUSIONS: Compared with 12hCIT, posttransplant pathophysiology
      deteriorated similarly in both 18hCIT and WIT groups. However, tissue adenosine
      triphosphate levels and inflammatory profiling differed between warm versus cold
      ischemic donor lungs. These differences should be carefully considered when
      developing specific therapeutic strategies to reduce ischemia-reperfusion injury
      in lung transplantation.

PMID- 29470356
TI  - Donor Club Cell Secretory Protein G38A Polymorphism Is Associated With a
      Decreased Risk of Primary Graft Dysfunction in the French Cohort in Lung
      Transplantation.
AB  - BACKGROUND: Club Cell Secretory Protein (CCSP) G38A polymorphism has recently
      been involved in lung epithelial susceptibility to external injuries. Lung
      transplantation (LT) is currently limited by ischemia-reperfusion injury leading
      to primary graft dysfunction (PGD). We thus hypothesized that donor CCSP G38A
      polymorphism might impact the risk of PGD after LT. METHODS: We focused on LT
      included in the French multicentric Cohort in Lung Transplantation (COLT),
      performed between January 2009 and December 2014, and associated with
      preoperative blood samples from the donor and the recipient. Characteristics of
      the donors, recipients, procedures, early and late outcomes were prospectively
      recorded in COLT. The CCSP serum concentration and CCSP gene G38A polymorphism
      were retrospectively determined in a blind manner. Their association with grade 3
      PGD was studied in univariate and multivariate analysis. RESULTS: The study group
      included 104 LT donors and recipients, 84 with grade 0 to 2 PGD and 20 with grade
      3 PGD. Preoperative CCSP serum concentration was significantly higher in the
      donors (median, 22.54 ng/mL; interquartile range, 9.6-43.9) than in the
      recipients (median, 7.03 ng/mL; interquartile range, 0.89-19.2; P < 0.001) but
      none impacted the risk of grade 3 PGD (P = 0.93 and P = 0.69, respectively).
      Donor CCSP G38A polymorphism was associated with a decreased risk of grade 3 PGD
      in univariate (AG + AA 3/21 = 14.2% vs GG 10/26 = 38.4%, P = 0.044) and
      multivariate analysis (odds ratio associated with AG + AA, 0.22; 95% confidence
      interval, 0.041-0.88; P = 0.045), but recipient CCSP G38A polymorphism was not.
      CONCLUSIONS: Donor CCSP G38A polymorphism is associated with a decreased risk of
      severe PGD after LT in the COLT study. These findings should be confirmed in the
      frame of a prospective study.

PMID- 29470357
TI  - Validation of the alpha-fetoprotein Model for Hepatocellular Carcinoma Recurrence
      After Transplantation in an Asian Population.
AB  - BACKGROUND: This study was designed to validate the alpha-fetoprotein model for
      predicting recurrence after liver transplantation in Korean hepatocellular
      carcinoma patients. METHODS: Patients who underwent liver transplantation for
      hepatocellular carcinoma at Samsung Medical Center between 2007 and 2015 were
      included. Recurrence, overall survival, and disease-specific survival of patients
      divided by both the Milan criteria and the alpha-fetoprotein model were compared
      using Kaplan-Meier log-rank test. The predictability of the alpha-fetoprotein
      model compared with the Milan criteria was tested by means of net
      reclassification improvement analysis applied to patients with a follow-up of at
      least 2 years. RESULTS: A total of 400 patients were included in the study.
      Patients within Milan criteria had 5-year recurrence, and overall survival rates
      of 20.9% and 76.3%, respectively, compared with corresponding rates of 50.3% and
      55.7%, respectively, for patients who were beyond Milan criteria. alpha
      Fetoprotein model low-risk patients had 5-year recurrence and overall survival
      rates of 21.1% and 76.2%, respectively, compared with corresponding rates of
      57.7% and 52.2%, respectively, in high-risk patients (P < 0.001, all). Although
      overall net reclassification improvements were statistically nonsignificant for
      recurrence (net reclassification improvements [NRI] = 1.7%, Z = 0.30, P =
      0.7624), and overall survival (NRI = 9.0%, Z = 1.60, P = 0.1098), they were
      significantly better for predicting no recurrence (NRI = 6.6%, Z = 3.16, P =
      0.0016) and no death. (NRI = 7.7%, Z = 3.65, P = 0.0003). CONCLUSIONS: The alpha
      fetoprotein model seems to be a promising tool for liver transplantation
      candidacy, but further investigation is needed.

PMID- 29470359
TI  - CD44 Deficiency in Mice Protects the Heart Against Angiotensin II-Induced Cardiac
      Fibrosis.
AB  - This study tested the hypothesis that CD44 is involved in development of cardiac
      fibrosis via angiotensin II (Ang II) AT1 receptor stimulated
      TNFalpha/NFkappaB/IkappaB signaling pathways. Study was conducted in C57BL/6 wild
      type and CD44 knockout mice subjected to Ang II infusion (1000 ng/kg/min) using
      osmotic minipumps up to 4 weeks or with gastric gavage administration of the AT1
      receptor blocker, telmisartan at a dose of 10 mg/kg/day. Results indicated that
      Ang II enhances expression of the AT1 receptor, TNFalpha, NFkappaB and CD44 as
      well as downregulates IkappaB. Further analyses revealed that Ang II increases
      macrophage migration, augments myofibroblast proliferation and induces
      vascular/interstitial fibrosis. Comparison of the Ang II group, treatment with
      telmisartan significantly reduced expression of the AT1 receptor and TNFalpha.
      These changes occurred in coincidence with decreased NFkappaB, increased IkappaB
      and downregulated CD44 in the intracardiac vessels and intermyocardium.
      Furthermore, macrophage migration and myofibroblast proliferation were inhibited
      and fibrosis was attenuated. Knockout of CD44 did not affect Ang II stimulated
      AT1 receptor and modulated TNFalpha/NFkappaB/IkappaB signaling, but significantly
      reduced macrophage/myofibroblast mediated fibrosis as identified by less
      extensive collagen-rich area. These results suggest that the AT1 receptor is
      involved in the development of cardiac fibrosis by stimulating
      TNFalpha/NFkappaB/IkappaB triggered CD44 signaling pathways. Knockout of CD44
      blocked Ang II induced cell migration/proliferation and cardiac fibrosis.
      Therefore, selective inhibition of CD44 may be considered as a potential
      therapeutic target for attenuating Ang II induced deleterious cardiovascular
      effects.

PMID- 29470358
TI  - Is Vulvovaginal Lichen Planus Associated With Squamous Cell Carcinoma?
AB  - OBJECTIVE: The aim of the study was to assess for the presence of vulvar lichen
      planus (LP) in association with human papillomavirus (HPV)-independent squamous
      cell carcinoma (SCC). MATERIALS AND METHODS: We performed a
      clinicohistopathologic review of consecutive vulvectomies and wide local
      excisions for HPV-independent vulvar or vaginal SCC from 2007 to 2017. Data
      collected included site of SCC, adjacent precursor lesions and dermatoses,
      dermatologic treatment, and outcome. RESULTS: There were 43 cases of primary HPV
      independent vulvar SCC treated by excision, but no vaginal cancers. Eighteen
      women (42%) had a preoperative diagnosis of lichen sclerosus (LS); none had a
      diagnosis of LP. Topical corticosteroids were prescribed in 19 (44%) of 43, with
      4 women placed on maintenance therapy. Tumors arose from the labia minora, labia
      majora, and periclitoris, but not from vestibule or perianus. On
      histopathological review, LS was present in 41 (95%) of 43 specimens, 1 had a
      nonspecific lichenoid reaction, and 1 had lichen simplex; both of the latter had
      subsequent biopsies showing LS. Lichen planus was not seen in association with
      SCC. Differentiated vulvar intraepithelial neoplasia (dVIN) was present in 38
      (88%) of 43 specimens, whereas 1 had acanthosis with altered differentiation and
      4 (9%) had no precursor lesion. Differentiated vulvar intraepithelial neoplasia
      had standard, basaloid, and hypertrophic morphology, superficially resembling
      erosive LP in 9 (24%) of 38 and hypertrophic LP in 6 (16%) of 38. CONCLUSIONS:
      Lichen planus was not seen in association with HPV-independent vulvar SCC,
      whereas LS was underrecognized and inadequately treated in this group.
      Pathologists should be aware that dVIN may superficially resemble erosive or
      hypertrophic LP.

PMID- 29470360
TI  - Oral Supplementation with Bovine Colostrum Prevents Septic Shock and Brain
      Barrier Disruption During Bloodstream Infection in Preterm Newborn Pigs.
AB  - Preterm infants have increased risk of neonatal sepsis, potentially inducing
      brain injury, and they may benefit from early initiation of enteral milk feeding.
      Using preterm pigs as models, we hypothesized that early provision of bovine
      colostrum to parentally nourished newborns protects against sepsis and
      neuroinflammation during bloodstream infection. Preterm newborn pigs were
      administered 10 CFU/kg of intra-arterial Staphylococcus epidermidis (SE, an
      opportunistic pathogen often causing sepsis in preterm infants), followed by
      administration of total parenteral nutrition (TPN, SE + TPN, n = 15) or oral
      provision of bovine colostrum with supplementary parenteral nutrition (SE + COL,
      n = 14), and compared with uninfected, TPN-nourished controls (CON + TPN, n =
      11). SE-infected animals showed multiple signs of sepsis, including lethargy,
      hypotension, respiratory acidosis, internal organ hemorrhages, cellular responses
      (leukopenia, thrombocytopenia), brain barrier disruption and neuroinflammation.
      At 24 h, colostrum supplementation reduced the SE abundance in blood and
      cerebrospinal fluid (CSF, both p < 0.05). Further, colostrum feeding normalized
      arterial blood pressure (38.5 +/- 1.20 vs 30.6 +/- 3.79 mmHg), pH (7.37 +/- 0.02
      vs 7.10 +/- 0.07) and lactate (1.01 +/- 0.11 vs 4.20 +/- 1.20 mM, all p < 0.05),
      and increased motor activity, to levels in controls (p < 0.001). Finally,
      colostrum-fed animals showed reduced blood-CSF barrier permeability and CSF
      leukocyte levels, and this was accompanied by normalized gene expression of tight
      junction proteins (Occludin, Claudin-5, both p < 0.05) and reduced expression of
      leukocyte chemoattractants (CXCL9-11, all p < 0.01). Early oral supplementation
      with bovine colostrum prevents septic shock and ameliorates brain barrier
      disruption and neuroinflammation during bloodstream infection in preterm pigs.
      Bovine colostrum supplementation may improve resistance against systemic
      infection in immature, immune-compromised preterm infants.

PMID- 29470361
TI  - Early Heterogenic Response of Renal Microvasculature to Hemorrhagic
      Shock/Resuscitation and the Influence of NF-kappaB Pathway Blockade.
AB  - Hemorrhagic shock (HS) is associated with low blood pressure due to excessive
      loss of circulating blood and causes both macrocirculatory and microcirculatory
      dysfunction. Fluid resuscitation after HS is used in the clinic to restore tissue
      perfusion. The persistent microcirculatory damage caused by HS and/or
      resuscitation can result in multiple organ damage, with the kidney being one of
      the involved organs. The kidney microvasculature consists of different segments
      that possess a remarkable heterogeneity in functional properties. The aim of this
      study was to investigate the inflammatory responses of these different renal
      microvascular segments, i.e., arterioles, glomeruli, and postcapillary venules,
      to HS and resuscitation (HS/R) in mice and to explore the effects of intervention
      with an NF-kappaB inhibitor on these responses. We found that HS/R disturbed the
      balance of the Angiopoietin-Tie2 ligand-receptor system, especially in the
      glomeruli. Furthermore, endothelial adhesion molecules, pro-inflammatory
      cytokines, and chemokines were markedly upregulated by HS/R, with the strongest
      responses occurring in the glomerular and postcapillary venous segments. Blockade
      of NF-kappaB signaling during the resuscitation period only slightly inhibited
      HS/R induced inflammatory activation, possibly because NF-kappaB p65 nuclear
      translocation already occurred during the HS period. In summary, although all
      three renal microvascular segments were activated upon HS/R, responses of
      endothelial cells in glomeruli and postcapillary venules to HS/R, as well as to
      NF-kappaB inhibition were stronger than those in arterioles. NF-kappaB inhibition
      during the resuscitation phase does not effectively counteract NF-kappaB p65
      nuclear translocation initiating inflammatory gene transcription.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- 29470362
TI  - An Evaluation of Supramaximally Loaded Eccentric Leg Press Exercise.
AB  - Harden, M, Wolf, A, Russell, M, Hicks, KM, French, D, and Howatson, G. An
      evaluation of supramaximally loaded eccentric leg press exercise. J Strength Cond
      Res 32(10): 2708-2714, 2018-High-intensity eccentric exercise is a potent
      stimulus for neuromuscular adaptation. A greater understanding of the mechanical
      stimuli afforded by this exercise will aid the prescription of future eccentric
      training regimens. This study sought to investigate the mechanical
      characteristics of supramaximally loaded eccentric exercise when using a custom
      built leg press machine. Using a within-subject, repeated-measures design, 15
      strength trained subjects (age, 31 +/- 7 years; height, 180.0 +/- 6.8 cm; body
      mass, 81.5 +/- 13.9 kg) were assessed under 3 different conditions: low (LO),
      moderate (MOD), and high (HI) intensity, which were equivalent in intensity to
      110, 130, and 150%, respectively, of peak force during an isometric maximal
      voluntary contraction (IMVC) performed on leg press at 90 degrees  knee flexion.
      All loading conditions demonstrated a similar pattern of mechanical profile;
      however, the variables underpinning each profile showed significant (p < 0.01)
      load-dependent response (LO vs. MOD, MOD vs. HI, LO vs. HI) for all variables,
      except for average acceleration. Average force associated with each loading
      conditions exceeded IMVC but equated to a lower intensity than what was
      prescribed. Repetitions under higher relative load intensity stimulated greater
      average force output, faster descent velocity, greater magnitude of acceleration,
      shorter time under tension, and a decline in force output at the end range of
      motion. This research provides new data regarding the fundamental mechanical
      characteristics underpinning supramaximally loaded eccentric leg press exercise.
      The information gathered in the study provides a foundation for practitioners to
      consider when devising loading strategies and implementing or evaluating
      supramaximally loaded eccentric exercise when using a similar exercise and
      device.

PMID- 29470363
TI  - A physiological and sport-specific comparison between division I and division II
      Italian male Field Hockey players.
AB  - The purpose of the present study was to compare the anthropometric and
      performance profiles of division I (D1) and division II (D2) Italian field hockey
      players.Fifteen DI players and fifteen D2 players (age = 25.4 +/- 5.2 y; body
      mass = 78.5 +/- 9.0 kg; body height = 179.6 +/- 7.8 cm) were assessed on one
      occasion for anthropometry, body composition, physiological measurements and
      sport-specific skills. Differences between the two groups were evaluated using a
      one-way analysis of variance. Pearson correlations were used to examine
      relationships between the different measurements.Significantly (p = 0.039) lower
      percentages of body fat were found on D1 group compared to D2 group (-3.5%). A
      significant difference between the groups were noted for shooting accuracy (p =
      0.013), with the D1 group performing 14.5 % better than the DII group. No
      significant differences between the groups were found for shooting speed (p =
      0.103), slalom and dribbling performances (p = 0.292 and p = 0.416,
      respectively). Physiological assessments did not show any significant differences
      between the groups. Large correlations (r = 0.73; p < 0.001) were found between
      shooting speed and accuracy. Moderate correlations were observed between the
      shooting speed and the hand grip strength, in particular of the left hand (r =
      0.61; p = 0.007).Results of the present study indicate that the difference
      between D1 and D2 players may be more related to technical factors than to
      physical fitness. Ball control however, may not be a limiting factor in D2
      players.

PMID- 29470364
TI  - Resistance Training Is Associated With Higher Bone Mineral Density Among Young
      Adult Male Distance Runners Independent of Physiological Factors.
AB  - Duplanty, AA, Levitt, DE, Hill, DW, McFarlin, BK, DiMarco, NM, and Vingren, JL.
      Resistance training is associated with higher bone mineral density among young
      adult male distance runners independent of physiological factors. J Strength Cond
      Res 32(6): 1594-1600, 2018-Low bone mineral density (BMD) in male distance
      runners is common and could be modulated by a host of biomarkers involved in the
      dynamic balance of bone tissue. In contrast, resistance training can increase
      BMD; however, the efficacy of resistance training in protecting BMD in distance
      runners has not been elucidated. The aim of this study was to investigate the
      relationship between resistance training, testosterone and bone metabolism
      biomarker concentrations, and BMD in young adult male distance runners. Twenty
      five apparently healthy men (23-32 years; mean +/- SD: 25.9 +/- 2.9 years; 1.77
      +/- 0.04 m; 75.4 +/- 8.5 kg) were categorized into 1 of 3 groups: untrained
      control participants (CON; n = 8); nonresistance-trained runners (NRT; n = 8); or
      resistance-trained runners (RT; n = 9). Blood was collected and analyzed for
      concentrations of free and total testosterone and 14 bone metabolism biomarkers.
      Bone mineral density was assessed using dual-energy X-ray absorptiometry. At all
      measured sites, BMD was greater (p <= 0.05) for RT compared with NRT and CON.
      Vitamin D concentration was greater (p <= 0.05) in RT and NRT compared with CON.
      Concentrations of testosterone and remaining bone biomarkers did not differ
      between groups (p > 0.05). Resistance-trained runners had greater BMD than
      nonresistance-trained runners and untrained peers. This difference did not seem
      to be modulated by biomarkers that contribute to bone formation or resorption,
      indicating that differences in BMD are associated with habitual load-bearing
      exercise using external resistance. Runners should perform resistance exercise at
      least once per week because this is associated with greater BMD.

PMID- 29470365
TI  - Effect of Acute Complex Training on Upper Body Force and Power in Collegiate
      Wrestlers.
AB  - To determine if chain bench press (BP) exercise would enhance acute upper body
      force and power, 13 collegiate male wrestlers (mean +/- SD; 20.5 +/- 1 years;
      174.3 +/- 4.2 cm; 76.5 +/- 8.3 kg) with >= 1 year of strength training
      participated. Session 1 included body composition ((BodPod) 8.5 +/- 2.6 %body
      fat)), 3 repetition maximum (RM) BP, and familiarization with the plyometric push
      up (PPU) on a force plate. Athletes were matched for 3RM BP and randomly assigned
      to one of two groups: Chain BP or Plate BP. One week after Session 1, athletes
      performed the experimental protocol which consisted of: Baseline PPU, Chain/Plate
      BP Set 1 (6 reps @ 60%), 30 sec rest, PPU, 3 min rest, Chain/Plate BP Set 2 (6
      reps @60%), 30 sec rest, and PPU. Independent samples t-tests analyzed physical
      characteristics (p<0.05). Standardized magnitude-based inferences were used to
      define outcomes. Aside from age (Plate BP 21.4 +/- 0.8, Chain BP 19.9 +/-0.7
      years), no physical differences were observed. Performance of Chain BP and Plate
      BP resulted in a likely (likelihoods of benefit/trivial/harm relative to the
      threshold for a smallest worthwhile benefit of 89 W: 0.5/9.2/90.3) and very
      likely (0.1/0.8/99.1) negative effect on peak power output in the PPU following
      Set 1. Chain BP resulted in a likely positive effect on peak force in the PPU
      following Set 1 (smallest worthwhile benefit 13 N: 82.8/16.9/0.3) and Set 2
      (94.7/5.2/0.1). Chain BP did not result in higher upper body power over
      traditional plate loaded resistances.

PMID- 29470366
TI  - Impact of angiotensin-converting enzyme inhibition on platelet tissue factor
      expression in stroke-prone rats.
AB  - OBJECTIVE: Hypertension is a well known risk factor for thrombotic events such as
      myocardial infarction and stroke. Platelets express tissue factor (TF), the key
      activator of blood coagulation and thrombus formation. The number of TF-positive
      platelets increases in pathological conditions characterized by thrombotic
      complications but whether this occurs in hypertension is unknown. Here we
      investigated whether platelet TF expression is increased in a hypertensive status
      through a mechanism acting on megakaryocytes; the phenomenon could be modulated
      by antihypertensive drug as captopril; angiotensin (AngII) influences platelet TF
      expression. METHODS: Spontaneously hypertensive stroke prone (SHRSP) rats
      received standard diet (StD) or a Japanese high-salt permissive diet (JpD). After
      3 weeks, JpD animals were randomized to receive captopril or vehicle.
      Normotensive Wistar Kyoto (WKY) rats were used as controls. Cell-associated TF
      expression and activity were analyzed by flow cytometry and calibrated automated
      thrombogram, respectively. RESULTS: Hypertensive StD-SHRSP showed an increased
      number of TF-positive platelets compared with normotensive WKY. After JpD
      administration, SHRSP developed severe hypertension and renal damage; the number
      of TF-positive megakaryocytes significantly increased compared with StD-SHRSP
      resulting in a higher number of TF-positive platelets with a faster kinetic of
      thrombin generation. These effects were reverted by captopril. Ex-vivo
      stimulation of platelets, isolated from normotensive WKY and from healthy
      individuals, with AngII induced a concentration-dependent increase of surface
      associated TF expression. CONCLUSION: The current study shows for the first time
      that in hypertension the number of TF-positive megakaryocytes increases thus
      releasing in the circulation more platelets carrying a functionally active TF.
      AngII stimulates platelets to express TF.

PMID- 29470367
TI  - What are the cardiovascular effects of the newer classes of drugs for type 2
      diabetes?
AB  - New classes of drugs to treat type 2 diabetes are continually being developed and
      marketed. The FDA has issued guidance to the pharmaceutical industry that newer
      hypoglycemic agents should not be associated with unacceptable increases in
      cardiovascular risk. To date, five trials have assessed specific cardiovascular
      endpoints for these newer agents. Empagliflozin and liraglutide have been found
      to improve cardiovascular outcomes.

PMID- 29470369
TI  - An unusual cause of an isolated scapula fracture.
AB  - This article reviews an isolated scapula fracture in a teenage athlete. Although
      rarely reported in professional athletes, scapula fracture should be included in
      the differential diagnosis of shoulder injuries. Proper imaging is key to
      effective diagnosis and management.

PMID- 29470370
TI  - Examining, diagnosing, and treating benign anorectal conditions.
AB  - Anorectal pain and discomfort are common complaints in the general population,
      and can stem from a number of possible causes. Often, the complaints present in
      the primary care setting and can be adequately evaluated, diagnosed, and treated
      without the need for referral to a colorectal specialist. Proper evaluation and
      diagnosis can result in prompt, effective patient care. Recognition of red flags
      should prompt immediate referral to a colorectal specialist for further
      evaluation.

PMID- 29470371
TI  - PA program characteristics and diversity in the profession.
AB  - OBJECTIVES: The primary objective of this study was to identify PA program
      characteristics that may be associated with higher or lower percentages of
      underrepresented minority students in PA programs. METHODS: Data from the
      Physician Assistant Education Association (PAEA) 2002-2003 and 2012-2013 annual
      surveys were analyzed. Bivariate correlation coefficients and multiple regression
      modeling were used to identify relationships between program characteristics and
      percentages of black and Hispanic students. RESULTS: The percentage of white
      matriculants in PA programs increased from 76.5% in 2002-2003 to 81.8% in 2012
      2013; the percentage of black students decreased from 6.2% to 4.4%. Multiple
      linear regression revealed a modest negative relationship between master's degree
      and percentage of underrepresented minority students and a modest positive
      relationship between percentages of underrepresented minority employees and
      underrepresented minority students. CONCLUSIONS: Further research is needed to
      identify strategies to increase underrepresented minority participation in
      healthcare professions programs.

PMID- 29470372
TI  - Improving veterans' access to gastroenterology clinical care.
AB  - At a VA hospital, wait times for gastroenterology care have been in the order of
      60 to 90 days for new clinic consults. Through a quality improvement process,
      these times were reduced to less than 30 days. With a revised triage process, the
      number of consults needing to be scheduled into the clinic was reduced 34%. In
      addition to achieving rapid clinical access, the weekly half-day clinic became
      less congested and more efficient. We describe this process of achieving improved
      access.

PMID- 29470373
TI  - Acute epididymitis.

PMID- 29470374
TI  - Ivabradine for systolic heart failure.
AB  - Ivabradine works in the sinoatrial node to prolong diastolic depolarization and
      reduce heart rate. In patients with chronic systolic heart failure, this drug has
      reduced the risk of hospitalization when used in combination with other optimal
      pharmacotherapy.

PMID- 29470375
TI  - What is this patient's mediastinal mass?

PMID- 29470376
TI  - Family matters.

PMID- 29470377
TI  - One specimen cup at a time.

PMID- 29470378
TI  - Preanesthesia concerns in a patient with a thyroid mass.
AB  - Preoperative evaluation helps identify patient comorbidities and surgical
      characteristics that increase perioperative risk, and also can help identify
      patients with potentially difficult airways. Identifying patients with difficult
      airways before surgery lets clinicians plan appropriate perioperative management
      and prepare for potential complications. This article focuses on management of a
      difficult airway in a patient undergoing surgery for a thyroid mass.

PMID- 29470380
TI  - Bringing Compassion Back to the Forefront of Care.

PMID- 29470381
TI  - The Business, Ethics, and Quality Cases for Consumer Engagement in Nursing.
AB  - OBJECTIVE: The aims of this study were to illustrate the quality, safety, cost
      effectiveness, and ethics of consumer engagement initiatives and identify
      promising practices and leadership strategies used by nursing leaders. METHODS: A
      literature review was performed with supplementary interviews conducted with 25
      key nursing informants including nursing executives and chief nursing officers at
      acute care hospitals, community health centers, policy institutions, and quality
      and safety organizations. A narrative synthesis approach was used to identify and
      compare existing measures of consumer engagement and compassionate care in acute
      care settings. One-hour semistructured interviews were performed, and information
      was gathered by notes and audio recordings. RESULTS: Consumer engagement
      activities focusing on compassionate patient and provider interactions involving
      patients and family as partners on the care team are associated with increases in
      treatment savings and patient safety in terms of length of stay and reduced
      medication errors. Engagement initiatives support employee health and reduce
      compassion fatigue. CONCLUSION: Findings illustrate the impact of patients and
      family engagement in decision making and promising organizational practices that
      reinforce engagement.

PMID- 29470382
TI  - A Tool to Identify Key Behaviors and Attributes of High-Performing Nurses.
AB  - OBJECTIVE: The purpose of this project was to identify key behaviors and
      attributes that distinguish high-performing nurses to develop a tool for
      employment screening, staff development, and performance management. BACKGROUND:
      Selecting nurses who will complement an organization's mission and philosophy is
      a key step toward achieving quality and safety goals, ensuring patient and family
      satisfaction, and improving retention rates and overall costs. METHODS: Focus
      group methodology was used to determine perceptions of high-performing nurses'
      behaviors and attributes. Content analysis of the meeting transcripts was
      performed to aggregate data into categories and items. RESULTS: Following several
      phases of testing with various groups, a 16-item scale has been developed.
      CONCLUSIONS: This tool has received positive ratings from nurse managers
      currently using it to interview nurse applicants who best "fit" into the
      organization's nursing culture. Results will be monitored over time including
      hiring decisions, preceptor ratings, and retention rates.

PMID- 29470383
TI  - Participating in a Multisite Study Exploring Operational Failures Encountered by
      Frontline Nurses: Lessons Learned.
AB  - This article describes our experience participating in a multisite collaborative
      study involving frontline nurses and operational failures (OFs). We encountered a
      range of challenges conducting the study as proposed by the study's coordinating
      center (CC), which hindered our ability to meet our goals and objectives. We
      identified 3 general areas in which our expectations and actual experience
      diverged: 1) research resources, design, and methods; 2) CC communications and
      deliverables; and 3) influencing organizational change. Nurse executives
      considering collaborative research or assessing methods to engage clinical nurses
      in organizational improvements will benefit from our experience.

PMID- 29470384
TI  - Continuous Improvement and Employee Engagement, Part 2: Design, Implementation,
      and Outcomes of a Daily Management System.
AB  - A daily management system (DMS) can be used to implement continuous quality
      improvement and advance employee engagement. It can empower staff to identify
      problems in the care environment that impact quality or work flow and to address
      them on a daily basis. Through a DMS, improvement becomes the work of everyone,
      every day. The authors of this 2-part series describe their work to develop a
      DMS. Part 2 describes the implementation and outcomes of the program.

PMID- 29470385
TI  - An Activity Recognition Framework Deploying the Random Forest Classifier and A
      Single Optical Heart Rate Monitoring and Triaxial AccelerometerWrist-Band.
AB  - Wrist-worn sensors have better compliance for activity monitoring compared to
      hip, waist, ankle or chest positions. However, wrist-worn activity monitoring is
      challenging due to the wide degree of freedom for the hand movements, as well as
      similarity of hand movements in different activities such as varying intensities
      of cycling. To strengthen the ability of wrist-worn sensors in detecting human
      activities more accurately, motion signals can be complemented by physiological
      signals such as optical heart rate (HR) based on photoplethysmography. In this
      paper, an activity monitoring framework using an optical HR sensor and a triaxial
      wrist-worn accelerometer is presented. We investigated a range of daily life
      activities including sitting, standing, household activities and stationary
      cycling with two intensities. A random forest (RF) classifier was exploited to
      detect these activities based on the wrist motions and optical HR. The highest
      overall accuracy of 89.6 +/- 3.9% was achieved with a forest of a size of 64
      trees and 13-s signal segments with 90% overlap. Removing the HR-derived features
      decreased the classification accuracy of high-intensity cycling by almost 7%, but
      did not affect the classification accuracies of other activities. A feature
      reduction utilizing the feature importance scores of RF was also carried out and
      resulted in a shrunken feature set of only 21 features. The overall accuracy of
      the classification utilizing the shrunken feature set was 89.4 +/- 4.2%, which is
      almost equivalent to the above-mentioned peak overall accuracy.

PMID- 29470386
TI  - Bioactive Phenolic and Isocoumarin Glycosides from the Stems of Homalium
      paniculiflorum.
AB  - Two new phenolic glycosides (1 and 2) and two new isocoumarin glycosides (3 and
      4), along with 14 known compounds (5-18), were isolated from the stems of
      Homalium paniculiflorum. Their structures were established on the basis of
      extensive spectroscopic analyses and chemical methods. All new compounds were
      evaluated for their anti-inflammatory activities via examining the inhibitory
      activity on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in
      mouse macrophage RAW 264.7 cells in vitro. Compounds 1 and 4 exhibited inhibitory
      activities with IC50 values of 30.23 +/- 1.23 MUM and 19.36 +/- 0.19 MUM,
      respectively.

PMID- 29470387
TI  - Assessment of Chitosan-Based Hydrogel and Photodynamic Inactivation against
      Propionibacterium acnes.
AB  - Chitosan (CH) is a biopolymer that exhibits a number of interesting properties
      such as anti-inflammatory and antibacterial activity and is also a promising
      platform for the incorporation of photosensitizing agents. This study aimed to
      evaluate the efficacy of antimicrobial activity of chitosan hydrogel formulation
      alone and in combination with the methylene blue (MB) associated with
      antimicrobial photodynamic therapy (aPDT) against planktonic and biofilm phase of
      Propionibacterium acnes. Suspensions were sensitized with 12.5, 25.0, 37.5, 50.0
      MUg/mL of MB for 10 min and biofilms to 75, 100 and 150 MUg/mL for 30 min then
      exposed to red light (660 nm) at 90 J/cm2 and 150 J/cm2 respectively. After
      treatments, survival fractions were calculated by counting the number of colony
      forming units. The lethal effect of aPDT associated with CH hydrogel in
      planktonic phase was achieved with 12.5 ug/mL MB and 1.9 log10 biofilm reduction
      using 75 ug/mL MB. Rheological studies showed that formulations exhibited
      pseudoplastic non-Newtonian behavior without thixotropy. Bioadhesion test
      evidenced that the formulations are highly adhesive to skin and the incorporation
      of MB did not influence the bioadhesive force of the formulations.

PMID- 29470388
TI  - Adolescents' Sexual Wellbeing in Southwestern Uganda: A Cross-Sectional
      Assessment of Body Image, Self-Esteem and Gender Equitable Norms.
AB  - Measures of sexual wellbeing and positive aspects of sexuality in the World
      Health Organization definition for sexual health are rarely studied and remain
      poorly understood, especially among adolescents in Sub-Saharan Africa. The
      objective of this study was to assess sexual wellbeing in its broad sense-i.e.,
      body image, self-esteem, and gender equitable norms-and associated factors in
      young adolescents in Uganda. A cross-sectional survey of adolescents ages 10-14
      years in schools was carried out between June and July 2016. Among 1096
      adolescents analyzed, the median age was 12 (Inter-Quartile Range (IQR): 11, 13)
      and 58% were female. Self-esteem and body image scores were high with median 24
      (IQR: 22, 26, possible range: 7-28) and median 22 (IQR: 19, 24, possible range: 5
      25) respectively. Gender equitable norms mean score was 28.1 (SD 5.2: possible
      range 11-44). We noted high scores for self-esteem and body image but moderate
      scores on gender equitable norms. Girls had higher scores compared to boys for
      all outcomes. A higher age and being sexually active were associated with lower
      scores on gender equitable norms. Gender equitable norms scores decreased with
      increasing age of adolescents. Comprehensive and timely sexuality education
      programs focusing on gender differences and norms are recommended.

PMID- 29470389
TI  - A Walnut-Enriched Diet Affects Gut Microbiome in Healthy Caucasian Subjects: A
      Randomized, Controlled Trial.
AB  - Regular walnut consumption is associated with better health. We have previously
      shown that eight weeks of walnut consumption (43 g/day) significantly improves
      lipids in healthy subjects. In the same study, gut microbiome was evaluated. We
      included 194 healthy subjects (134 females, 63 +/- 7 years, BMI 25.1 +/- 4.0
      kg/m2) in a randomized, controlled, prospective, cross-over study. Following a
      nut-free run-in period, subjects were randomized to two diet phases (eight weeks
      each); 96 subjects first followed a walnut-enriched diet (43 g/day) and then
      switched to a nut-free diet, while 98 subjects followed the diets in reverse
      order. While consuming the walnut-enriched diet, subjects were advised to either
      reduce fat or carbohydrates or both to account for the additional calories. Fecal
      samples were collected from 135 subjects at the end of the walnut-diet and the
      control-diet period for microbiome analyses. The 16S rRNA gene sequencing data
      was clustered with a 97% similarity into Operational Taxonomic Units (OTUs).
      UniFrac distances were used to determine diversity between groups. Differential
      abundance was evaluated using the Kruskal-Wallis rank sum test. All analyses were
      performed using Rhea. Generalized UniFrac distance shows that walnut consumption
      significantly affects microbiome composition and diversity. Multidimensional
      scaling (metric and non-metric) indicates dissimilarities of approximately 5%
      between walnut and control (p = 0.02). The abundance of Ruminococcaceae and
      Bifidobacteria increased significantly (p < 0.02) while Clostridium sp. cluster
      XIVa species (Blautia; Anaerostipes) decreased significantly (p < 0.05) during
      walnut consumption. The effect of walnut consumption on the microbiome only
      marginally depended on whether subjects replaced fat, carbohydrates or both while
      on walnuts. Daily intake of 43 g walnuts over eight weeks significantly affects
      the gut microbiome by enhancing probiotic- and butyric acid-producing species in
      healthy individuals. Further evaluation is required to establish whether these
      changes are preserved during longer walnut consumption and how these are linked
      to the observed changes in lipid metabolism.

PMID- 29470390
TI  - Preparation of Fish Skin Gelatin-Based Nanofibers Incorporating Cinnamaldehyde by
      Solution Blow Spinning.
AB  - Cinnamaldehyde, a natural preservative that can non-specifically deactivate
      foodborne pathogens, was successfully incorporated into fish skin gelatin (FSG)
      solutions and blow spun into uniform nanofibers. The effects of cinnamaldehyde
      ratios (5-30%, w/w FSG) on physicochemical properties of fiber-forming emulsions
      (FFEs) and their nanofibers were investigated. Higher ratios resulted in higher
      values in particle size and viscosity of FFEs, as well as higher values in
      diameter of nanofibers. Loss of cinnamaldehyde was observed during solution blow
      spinning (SBS) process and cinnamaldehyde was mainly located on the surface of
      resultant nanofibers. Nanofibers all showed antibacterial activity by direct
      diffusion and vapor release against Escherichia coli O157:H7, Salmonella
      typhimurium, and Listeria monocytogenes. Inhibition zones increased as
      cinnamaldehyde ratio increased. Nanofibers showed larger inhibition effects than
      films prepared by casting method when S. typhimurium was exposed to the released
      cinnamaldehyde vapor, although films had higher remaining cinnamaldehyde than
      nanofibers after preparation. Lower temperature was favorable for cinnamaldehyde
      retention, and nanofibers added with 10% cinnamaldehyde ratio showed the highest
      retention over eight-weeks of storage. Results suggest that FSG nanofibers can be
      prepared by SBS as carriers for antimicrobials.

PMID- 29470391
TI  - Experimental L-Band Airborne SAR for Oil Spill Response at Sea and in Coastal
      Waters.
AB  - Satellite synthetic aperture radar (SAR) is frequently used during oil spill
      response efforts to identify oil slick extent, but suffers from the major
      disadvantages of potential long latency between when a spill occurs and when a
      satellite can image the site and an inability to continuously track the spill as
      it develops. We show using data acquired with the Uninhabited Aerial Vehicle SAR
      (UAVSAR) instrument how a low noise, high resolution, L-band SAR could be used
      for oil spill response, with specific examples of tracking slick extent, position
      and weathering; determining zones of relatively thicker or more emulsified oil
      within a slick; and identifying oil slicks in coastal areas where look-alikes
      such as calm waters or biogenic slicks can confound the identification of mineral
      oil spills. From these key points, the essential features of an airborne SAR
      system for operational oil spill response are described, and further research
      needed to determine SAR's capabilities and limitations in quantifying slick
      thickness is discussed.

PMID- 29470392
TI  - GJA4/Connexin 37 Mutations Correlate with Secondary Lymphedema Following Surgery
      in Breast Cancer Patients.
AB  - Lymphedema is a condition resulting from mutations in various genes essential for
      lymphatic development and function, which leads to obstruction of the lymphatic
      system. Secondary lymphedema is a progressive and incurable condition, most often
      manifesting after surgery for breast cancer. Although its causation appears
      complex, various lines of evidence indicate that genetic predisposition may play
      a role. Previous studies show that mutations in connexin 47 are associated with
      secondary lymphedema. We have tested the hypothesis that connexin 37 gene
      mutations in humans are associated with secondary lymphedema following breast
      cancer surgery. A total of 2211 breast cancer patients were screened and tested
      for reference single nucleotide polymorphisms (SNPs) of the GJA4 gene (gap
      junction protein alpha 4 gene). The results presented in this paper indicate that
      two SNPs in the 3' UTR (the three prime untranslated region) of the GJA4 gene are
      associated with an increased risk of secondary lymphedema in patients undergoing
      breast cancer treatment. Our results provide evidence of a novel genetic
      biomarker for assessing the predisposition to secondary lymphedema in human
      breast cancer patients. Testing for the condition-associated alleles described
      here could assist and inform treatment and post-operative care plans of breast
      cancer patients, with potentially positive outcomes for the management of disease
      progression.

PMID- 29470393
TI  - DFT Insights into the Role of Relative Positions of Fe and N Dopants on the
      Structure and Properties of TiO2.
AB  - The location and nature of the doped elements strongly affect the structural,
      electronic and optical properties of TiO2. To tailor the band structure and
      modify the photoelectrochemical properties of TiO2, a pair of dopants is
      selected. Fe and N atoms are inserted in the TiO2 network at substitutional and
      interstitial sites with different relative distances. The main objective behind
      the different locations and sites of the doped elements is to banish the isolated
      unoccupied states from the forbidden region that normally annihilates the
      photogenerated carriers. Fe at the Ti site and N at the O site doped in the TiO2
      network separated at a distance of 7.805 A provided a suitable configuration of
      dopant atoms in terms of geometry and band structure. Moreover, the optical
      properties showed a notable shift to the visible regime. Individual dopants
      either introduced isolated unoccupied states in the band gap or disturbed the
      fermi level and structural properties. Furthermore, the other co-doped
      configurations showed no remarkable band shift, as well as exhibiting a suitable
      band structure. Resultantly, comparing the band structure and optical properties,
      it is argued that Fe (at Ti) and N (at O) doped at a distance of 7.805 A would
      strongly improve the photoelectrochemical properties of TiO2.

PMID- 29470394
TI  - A Novel Early Warning System Based on a Sediment Microbial Fuel Cell for In Situ
      and Real Time Hexavalent Chromium Detection in Industrial Wastewater.
AB  - Hexavalent chromium (Cr(VI)) is a well-known toxic heavy metal in industrial
      wastewater, but in situ and real time monitoring cannot be achieved by current
      methods used during industrial wastewater treatment processes. In this study, a
      Sediment Microbial Fuel Cell (SMFC) was used as a biosensor for in situ real-time
      monitoring of Cr(VI), which was the organic substrate is oxidized in the anode
      and Cr(VI) is reduced at the cathode simultaneously. The pH 6.4 and temperature
      25  degrees C were optimal conditions for the operation. Under the optimal
      conditions, linearity (R2 = 0.9935) of the generated voltage was observed in the
      Cr(VI) concentration range from 0.2 to 0.7 mg/L. The system showed high
      specificity for Cr(VI), as other co-existing ions such as Cu2+, Zn2+, and Pb2+
      did not interfere with Cr(VI) detection. In addition, when the sediment MFC-based
      biosensor was applied for measuring Cr(VI) in actual wastewater samples, a low
      deviation (<8%) was obtained, which indicated its potential as a reliable
      biosensor device. MiSeq sequencing results showed that electrochemically active
      bacteria (Geobacter and Pseudomonas) were enriched at least two-fold on the
      biofilm of the anode in the biosensor as compared to the SMFC without Cr(VI).
      Cyclic voltammetry curves indicated that a pair of oxidation/reduction peaks
      appeared at -111 mV and 581 mV, respectively. These results demonstrated that the
      proposed sediment microbial fuel cell-based biosensor can be applied as an early
      warning device for real time in situ detection of Cr(VI) in industrial
      wastewaters.

PMID- 29470395
TI  - Therapeutic Potential of Oridonin and Its Analogs: From Anticancer and
      Antiinflammation to Neuroprotection.
AB  - Oridonin, a diterpenoid natural product commonly used in East Asian herbal
      medicine, is garnering increased attention in the biomedical community due to its
      extensive biological activities that include antitumor, anti-inflammatory,
      antimicrobial, hepatic fibrosis prevention, and neurological effects. Over the
      past decade, significant progress has been made in structure activity
      relationship and mechanism of action studies of oridonin for the treatment of
      cancer and other diseases. This review provides a brief summary on oridonin and
      its analogs in cancer drug discovery and antiinflammation and highlights its
      emerging therapeutic potential in neuroprotection applications.

PMID- 29470396
TI  - Sodium and Potassium Consumption in a Semi-Urban Area in Peru: Evaluation of a
      Population-Based 24-Hour Urine Collection.
AB  - Despite the negative effects of high sodium and low potassium consumption on
      cardiovascular health, their consumption has not been quantified in sites
      undergoing urbanization. We aimed to determine the sodium and potassium
      consumption in a semi-urban area in Peru with a cross-sectional study. 24-h urine
      samples were collected. The outcomes were mean consumption of sodium and
      potassium, as well as adherence to their consumption recommendation: <2 g/day and
      >=3.51 g/day, respectively. Bivariate analyses were conducted to identify socio
      economic and clinical variables associated with the consumption recommendations
      of 602 participants, complete urine samples were found in 409: mean age of
      participants was 45.7 (standard deviation (SD): 16.2) years and 56% were women.
      The mean sodium and potassium consumption was 4.4 (SD: 2.1) and 2.0 (SD: 1.2)
      g/day. The sodium and potassium recommendation was met by 7.1% and 13.7% of the
      study sample; none of the participants met both recommendations. People not
      adherent to the sodium recommendation had higher diastolic (73.1 mmHg vs. 68.2
      mmHg, p = 0.015) and systolic (113.1 mmHg vs. 106.3 mmHg, p = 0.047) blood
      pressure than those who comply with the recommendation. Public health actions
      ought to be implemented in areas undergoing urbanization to improve sodium and
      potassium consumption at the population level.

PMID- 29470398
TI  - Structural Designing of a MEMS Capacitive Accelerometer for Low Temperature
      Coefficient and High Linearity.
AB  - The low temperature coefficient and high linearity of the input-output
      characteristics are both required for high-performance microelectromechanical
      systems (MEMS) capacitive accelerometers. In this work, a structural designing of
      a bulk MEMS capacitive accelerometer is developed for both low temperature
      coefficient and high linearity. Firstly, the contrary effect of the wide-narrow
      gaps ratio (WNGR) on the temperature coefficient of the scale factor (TCSF) and
      linearity error is discussed. Secondly, the ability of an improved structure that
      can avoid the contrary effect is illustrated. The improved structure is proposed
      in our previous work for reducing the temperature coefficient of bias (TCB) and
      TCSF. Within the improved structure, both the TCSF and linearity error decrease
      with increasing WNGR. Then, the precise designing of the improved structure is
      developed for achieving lower TCB, TCSF, and linearity error. Finally, the
      precise structural designing is experimentally verified.

PMID- 29470397
TI  - The Alphavirus Exit Pathway: What We Know and What We Wish We Knew.
AB  - Alphaviruses are enveloped positive sense RNA viruses and include serious human
      pathogens, such as the encephalitic alphaviruses and Chikungunya virus.
      Alphaviruses are transmitted to humans primarily by mosquito vectors and include
      species that are classified as emerging pathogens. Alphaviruses assemble highly
      organized, spherical particles that bud from the plasma membrane. In this review,
      we discuss what is known about the alphavirus exit pathway during a cellular
      infection. We describe the viral protein interactions that are critical for virus
      assembly/budding and the host factors that are involved, and we highlight the
      recent discovery of cell-to-cell transmission of alphavirus particles via
      intercellular extensions. Lastly, we discuss outstanding questions in the
      alphavirus exit pathway that may provide important avenues for future research.

PMID- 29470399
TI  - A Novel Dicyanoisophorone-Based Ratiometric Fluorescent Probe for Selective
      Detection of Cysteine and Its Bioimaging Application in Living Cells.
AB  - A selective and ratiometric turn-on fluorescent probe was designed and
      synthesized by using a novel dicyanoisophorone-based derivative and acrylate
      moiety. The probe displayed high stability and good selectivity to cysteine (Cys)
      over homocysteine (Hcy) and glutathione (GSH). It also exhibited rapid response
      to Cys within 180 s. Most importantly, the fluorescence intensity ratio at 590
      and 525 nm (I590/I525) was linearly dependent on the Cys concentration in the
      range from 0 to 40 MUM and the detection limit calculated to be 0.48 MUM. This
      probe was also applied for bioimaging of intracellular Cys in living HeLa cells
      with low cytotoxicity.

PMID- 29470400
TI  - RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway
      Enrichment Analysis of Genes and Metabolites.
AB  - The value of metabolomics in translational research is undeniable, and
      metabolomics data are increasingly generated in large cohorts. The functional
      interpretation of disease-associated metabolites though is difficult, and the
      biological mechanisms that underlie cell type or disease-specific metabolomics
      profiles are oftentimes unknown. To help fully exploit metabolomics data and to
      aid in its interpretation, analysis of metabolomics data with other complementary
      omics data, including transcriptomics, is helpful. To facilitate such analyses at
      a pathway level, we have developed RaMP (Relational database of Metabolomics
      Pathways), which combines biological pathways from the Kyoto Encyclopedia of
      Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome
      DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database
      that maps genes and metabolites to biochemical/disease pathways and can readily
      be integrated into other existing software is currently lacking. For consistent
      and comprehensive analysis, RaMP enables batch and complex queries (e.g., list
      all metabolites involved in glycolysis and lung cancer), can readily be
      integrated into pathway analysis tools, and supports pathway overrepresentation
      analysis given a list of genes and/or metabolites of interest. For usability, we
      have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including
      a user-friendly RShiny web application, that supports basic simple and batch
      queries, pathway overrepresentation analysis given a list of genes or metabolites
      of interest, and network visualization of gene-metabolite relationships. The
      package also includes the raw database file (mysql dump), thereby providing a
      stand-alone downloadable framework for public use and integration with other
      tools. In addition, the Python code needed to recreate the database on another
      system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd).
      Updates for databases in RaMP will be checked multiple times a year and RaMP will
      be updated accordingly.

PMID- 29470401
TI  - The Major Fusarium Species Causing Maize Ear and Kernel Rot and Their
      Toxigenicity in Chongqing, China.
AB  - Fusarium verticillioides, F. proliferatum, and F. meridionale were identified as
      the predominant fungi among 116 Fusarium isolates causing maize ear and kernel
      rot, a destructive disease in Chongqing areas, China. The toxigenic capability
      and genotype were determined by molecular amplification and toxin assay. The
      results showed that the key toxigenic gene FUM1 was detected in 47 F.
      verticillioides and 19 F. proliferatum isolates. Among these, F. verticillioides
      and F. proliferatum isolates mainly produced fumonisin B1, ranging from 3.17 to
      1566.44, and 97.74 to 11,100.99 ug/g for each gram of dry hyphal weight, with the
      averages of 263.94 and 3632.88 ug/g, respectively, indicating the F. proliferatum
      isolates on average produced about an order of magnitude more fumonisins than F.
      verticillioides did in these areas, in vitro. Only NIV genotype was detected
      among 16 F. meridionale and three F. asiaticum isolates. Among these, 11 F.
      meridionale isolates produced NIV, varying from 17.40 to 2597.34 ug/g. ZEA and
      DON toxins were detected in 11 and 4 F. meridionale isolates, with the toxin
      production range of 8.35-78.57 and 3.38-33.41 ug/g, respectively. Three F.
      asiaticum isolates produced almost no mycotoxins, except that one isolate
      produced a small amount of DON. The findings provide us with insight into the
      risk of the main pathogenic Fusarium species and a guide for resistance breeding
      in these areas.

PMID- 29470402
TI  - Cost-Effectiveness of a Specialized Oral Nutritional Supplementation for
      Malnourished Older Adult Patients in Spain.
AB  - Malnutrition has been related to prolonged hospital stays, and to increases in
      readmission and mortality rates. In the NOURISH (Nutrition effect On Unplanned
      Readmissions and Survival in Hospitalized patients) study, administering a high
      protein oral nutritional supplement (ONS) containing beta-hydroxy-beta
      methylbutyrate (HP-HMB) to hospitalised older adult patients led to a significant
      improvement in survival compared with a placebo treatment. The aim of this study
      was to determine whether HP-HMB would be cost-effective in Spain. We performed a
      cost-effectiveness analysis from the perspective of the Spanish National Health
      System using time horizons of 90 days, 180 days, 1 year, 2 years, 5 years and
      lifetime. The difference in cost between patients treated with HP-HMB and placebo
      was ?332.75. With the 90 days time horizon, the difference in life years gained
      (LYG) between both groups was 0.0096, resulting in an incremental cost
      effectiveness ratio (ICER) of ?34,700.62/LYG. With time horizons of 180 days, 1
      year, 2 years, 5 years and lifetime, the respective ICERs were ?13,711.68,
      ?3377.96, ?2253.32, ?1127.34 and ?563.84/LYG. This analysis suggests that
      administering HP-HMB to older adult patients admitted to Spanish hospitals during
      hospitalisation and after discharge could be a cost-effective intervention that
      would improve survival with a reduced marginal cost.

PMID- 29470403
TI  - Cladodionen, a Cytotoxic Hybrid Polyketide from the Marine-Derived Cladosporium
      sp. OUCMDZ-1635.
AB  - A new hybrid polyketide, cladodionen (1), together with a new abscisic acid
      analogue, cladosacid (2), were isolated from the marine-derived fungus,
      Cladosporium sp. OUCMDZ-1635. Their structures, including the absolute
      configurations, were fully elucidated on the basis of spectroscopic analysis, ECD
      spectra, quantum chemical calculations, and chemical methods. Cladodionen (1)
      showed cytotoxic activities against MCF-7, HeLa, HCT-116, and HL-60 human cancer
      cell lines with IC50 values of 18.7, 19.1, 17.9, and 9.1 uM.

PMID- 29470405
TI  - Gentamicin-Releasing Mesoporous ZnO Structures.
AB  - Among metal oxides, zinc oxide (ZnO) is one of the most attractive materials
      thanks to its biocompatible and biodegradable properties along with the existence
      of various morphologies featuring piezoelectric, semiconducting and
      photocatalytic activities. All of these structures were successfully prepared and
      tested for numerous applications, including optoelectronics, sensors and
      biomedical ones. In the last case, biocompatible ZnO nanomaterials positively
      influenced cells growth and tissue regeneration as well, promoting wound healing
      and new bone formation. Despite showing high surface areas, ZnO morphologies
      generally lack an intrinsic mesoporous structure, strongly limiting the
      investigation of the corresponding drug loading and release properties. Within
      this scope, this study focuses on the adsorption and release properties of high
      surface area, mesoporous ZnO structures using gentamicin sulfate (GS), a well
      known antibiotic against bacterial infections especially in orthopedics. The
      particular ZnO morphology was achieved starting from sputtered porous zinc
      layers, finally converted into ZnO by thermal oxidation. By taking advantage of
      this mesoporous framework, GS was successfully adsorbed within the ZnO matrix and
      the kinetic release profile evaluated for up to seven days. The adsorption of GS
      was successfully demonstrated, with a maximum amount of 263 mg effectively loaded
      per gram of active material. Then, fast kinetic release was obtained in vitro by
      simple diffusion mechanism, thus opening further possibilities of smart pore and
      surface engineering to improve the controlled delivery.

PMID- 29470404
TI  - Oleanolic Acid Exerts Osteoprotective Effects and Modulates Vitamin D Metabolism.
AB  - Oleanolic acid (OA) is a triterpenoid with reported bone anti-resorption
      activities. The present study aimed to characterize its bone protective effects
      in vivo and to study its effects on vitamin D metabolism, both in vivo and in
      vitro. OA significantly increased bone mineral density, improved micro
      architectural properties, reduced urinary Ca excretion, increased 1,25(OH)2D3 and
      renal CYP27B1 mRNA expression in mature C57BL/6 ovariectomised (OVX) mice. OA
      also improved bone properties, Ca balance, and exerted modulatory effects on
      renal CYP27B1 and CYP24A1 expressions in aged normal female Sprague-Dawley rats.
      In addition, OA significantly increased renal CYP27B1 mRNA and promoter activity,
      and suppressed CYP24A1 mRNA and protein expressions in human proximal tubule HKC
      8 cells. OA exerted bone protective effects in mature OVX mice and aged female
      rats. This action on bone might be, at least in part, associated with its effects
      on Ca and vitamin D metabolism. The present findings suggest that OA is a
      potential drug candidate for the management of postmenopausal osteoporosis.

PMID- 29470406
TI  - A Spectral Reconstruction Algorithm of Miniature Spectrometer Based on Sparse
      Optimization and Dictionary Learning.
AB  - The miniaturization of spectrometer can broaden the application area of
      spectrometry, which has huge academic and industrial value. Among various
      miniaturization approaches, filter-based miniaturization is a promising
      implementation by utilizing broadband filters with distinct transmission
      functions. Mathematically, filter-based spectral reconstruction can be modeled as
      solving a system of linear equations. In this paper, we propose an algorithm of
      spectral reconstruction based on sparse optimization and dictionary learning. To
      verify the feasibility of the reconstruction algorithm, we design and implement a
      simple prototype of a filter-based miniature spectrometer. The experimental
      results demonstrate that sparse optimization is well applicable to spectral
      reconstruction whether the spectra are directly sparse or not. As for the non
      directly sparse spectra, their sparsity can be enhanced by dictionary learning.
      In conclusion, the proposed approach has a bright application prospect in
      fabricating a practical miniature spectrometer.

PMID- 29470407
TI  - Toxicity of Pristine and Chemically Functionalized Fullerenes to White Rot Fungus
      Phanerochaete chrysosporium.
AB  - Fullerenes are widely produced and applied carbon nanomaterials that require a
      thorough investigation into their environmental hazards and risks. In this study,
      we compared the toxicity of pristine fullerene (C60) and carboxylated fullerene
      (C60-COOH) to white rot fungus Phanerochaete chrysosporium. The influence of
      fullerene on the weight increase, fibrous structure, ultrastructure, enzyme
      activity, and decomposition capability of P. chrysosporium was investigated to
      reflect the potential toxicity of fullerene. C60 did not change the fresh and dry
      weights of P. chrysosporium but C60-COOH inhibited the weight gain at high
      concentrations. Both C60 and C60-COOH destroyed the fibrous structure of the
      mycelia. The ultrastructure of P. chrysosporium was changed by C60-COOH. Pristine
      C60 did not affect the enzyme activity of the P. chrysosporium culture system
      while C60-COOH completely blocked the enzyme activity. Consequently, in the
      liquid culture, P. chrysosporium lost the decomposition activity at high C60-COOH
      concentrations. The decreased capability in degrading wood was observed for P.
      chrysosporium exposed to C60-COOH. Our results collectively indicate that
      chemical functionalization enhanced the toxicity of fullerene to white rot fungi
      and induced the loss of decomposition activity. The environmental risks of
      fullerene and its disturbance to the carbon cycle are discussed.

PMID- 29470409
TI  - Social Image Captioning: Exploring Visual Attention and User Attention.
AB  - Image captioning with a natural language has been an emerging trend. However, the
      social image, associated with a set of user-contributed tags, has been rarely
      investigated for a similar task. The user-contributed tags, which could reflect
      the user attention, have been neglected in conventional image captioning. Most
      existing image captioning models cannot be applied directly to social image
      captioning. In this work, a dual attention model is proposed for social image
      captioning by combining the visual attention and user attention
      simultaneously.Visual attention is used to compress a large mount of salient
      visual information, while user attention is applied to adjust the description of
      the social images with user-contributed tags. Experiments conducted on the
      Microsoft (MS) COCO dataset demonstrate the superiority of the proposed method of
      dual attention.

PMID- 29470408
TI  - Flexible, Stretchable Sensors for Wearable Health Monitoring: Sensing Mechanisms,
      Materials, Fabrication Strategies and Features.
AB  - Wearable health monitoring systems have gained considerable interest in recent
      years owing to their tremendous promise for personal portable health watching and
      remote medical practices. The sensors with excellent flexibility and
      stretchability are crucial components that can provide health monitoring systems
      with the capability of continuously tracking physiological signals of human body
      without conspicuous uncomfortableness and invasiveness. The signals acquired by
      these sensors, such as body motion, heart rate, breath, skin temperature and
      metabolism parameter, are closely associated with personal health conditions.
      This review attempts to summarize the recent progress in flexible and stretchable
      sensors, concerning the detected health indicators, sensing mechanisms,
      functional materials, fabrication strategies, basic and desired features. The
      potential challenges and future perspectives of wearable health monitoring system
      are also briefly discussed.

PMID- 29470410
TI  - The Evolving Role of Multivitamin/Multimineral Supplement Use among Adults in the
      Age of Personalized Nutrition.
AB  - Micronutrient deficiencies occur in segments of the adult population in the
      United States. Multivitamin/multimineral supplements (MVMS) are widely used by
      this population, which reduces inadequacies in micronutrient intake, but the
      potential for exceeding tolerable upper intake levels in others should be
      considered. There are concerns associated with the excessive intake of certain
      nutrients, particularly folic acid, and potential untoward consequences. The
      advent of nutrigenomics and the enhanced ability to directly study the
      interactions between nutrition and genetic variants and expression will allow for
      the conduct of more targeted studies with specific endpoints and may ultimately
      lead to progress in the field of personalized nutrition. The role of MVMS in
      health maintenance and chronic disease prevention remains controversial.
      Conducting studies in this area has been hampered by, among other factors,
      inconsistent definitions of MVMS, ranging from as few as three vitamins to broad
      spectrum products containing more than two dozen vitamins and minerals. Results
      from some observational studies and large-scale, randomized, controlled trials
      suggest that MVMS may reduce the risk of some forms of cancer and, potentially,
      cardiovascular disease. The ongoing COcoa Supplement and Multivitamin Outcomes
      Study (COSMOS) is expected to build on this research and provide additional
      insights into these areas.

PMID- 29470412
TI  - The Prevailing Catalytic Role of Meteorites in Formamide Prebiotic Processes.
AB  - Meteorites are consensually considered to be involved in the origin of life on
      this Planet for several functions and at different levels: (i) as providers of
      impact energy during their passage through the atmosphere; (ii) as agents of
      geodynamics, intended both as starters of the Earth's tectonics and as activators
      of local hydrothermal systems upon their fall; (iii) as sources of organic
      materials, at varying levels of limited complexity; and (iv) as catalysts. The
      consensus about the relevance of these functions differs. We focus on the
      catalytic activities of the various types of meteorites in reactions relevant for
      prebiotic chemistry. Formamide was selected as the chemical precursor and various
      sources of energy were analyzed. The results show that all the meteorites and all
      the different energy sources tested actively afford complex mixtures of
      biologically-relevant compounds, indicating the robustness of the formamide-based
      prebiotic chemistry involved. Although in some cases the yields of products are
      quite small, the diversity of the detected compounds of biochemical significance
      underlines the prebiotic importance of meteorite-catalyzed condensation of
      formamide.

PMID- 29470411
TI  - Stroke-Like Episodes and Cerebellar Syndrome in Phosphomannomutase Deficiency
      (PMM2-CDG): Evidence for Hypoglycosylation-Driven Channelopathy.
AB  - Stroke-like episodes (SLE) occur in phosphomannomutase deficiency (PMM2-CDG), and
      may complicate the course of channelopathies related to Familial Hemiplegic
      Migraine (FHM) caused by mutations in CACNA1A (encoding CaV2.1 channel). The
      underlying pathomechanisms are unknown. We analyze clinical variables to detect
      risk factors for SLE in a series of 43 PMM2-CDG patients. We explore the
      hypothesis of abnormal CaV2.1 function due to aberrant N-glycosylation as a
      potential novel pathomechanism of SLE and ataxia in PMM2-CDG by using whole-cell
      patch-clamp, N-glycosylation blockade and mutagenesis. Nine SLE were identified.
      Neuroimages showed no signs of stroke. Comparison of characteristics between SLE
      positive versus negative patients' group showed no differences. Acute and chronic
      phenotypes of patients with PMM2-CDG or CACNA1A channelopathies show
      similarities. Hypoglycosylation of both CaV2.1 subunits (alpha1A and alpha2alpha)
      induced gain-of-function effects on channel gating that mirrored those reported
      for pathogenic CACNA1A mutations linked to FHM and ataxia. Unoccupied N
      glycosylation site N283 at alpha1A contributes to a gain-of-function by lessening
      CaV2.1 inactivation. Hypoglycosylation of the alpha2delta subunit also
      participates in the gain-of-function effect by promoting voltage-dependent
      opening of the CaV2.1 channel. CaV2.1 hypoglycosylation may cause ataxia and SLEs
      in PMM2-CDG patients. Aberrant CaV2.1 N-glycosylation as a novel pathomechanism
      in PMM2-CDG opens new therapeutic possibilities.

PMID- 29470413
TI  - Electrical/Mechanical Monitoring of Shape Memory Alloy Reinforcing Fibers
      Obtained by Pullout Tests in SMA/Cement Composite Materials.
AB  - Self-healing is an essential property of smart concrete structures. In contrast
      to other structural metals, shape memory alloys (SMAs) offer two unique effects:
      shape memory effects, and superelastic effects. Composites composed of SMA wires
      and conventional cements can overcome the mechanical weaknesses associated with
      tensile fractures in conventional concretes. Under specialized environments, the
      material interface between the cementitious component and the SMA materials plays
      an important role in achieving the enhanced mechanical performance and robustness
      of the SMA/cement interface. This material interface is traditionally evaluated
      in terms of mechanical aspects, i.e., strain-stress characteristics. However, the
      current work attempts to simultaneously characterize the mechanical load
      displacement relationships synchronized with impedance spectroscopy as a function
      of displacement. Frequency-dependent impedance spectroscopy is tested as an in
      situ monitoring tool for structural variations in smart composites composed of
      non-conducting cementitious materials and conducting metals. The artificial
      geometry change in the SMA wires is associated with an improved anchoring action
      that is compatible with the smallest variation in resistance compared with
      prismatic SMA wires embedded into a cement matrix. The significant increase in
      resistance is interpreted to be associated with the slip of the SMA fibers
      following the elastic deformation and the debonding of the SMA fiber/matrix.

PMID- 29470414
TI  - The Sitting-Height Index of Build, (Body Mass)/(Sitting Height)3, as an
      Improvement on the Body Mass Index for Children, Adolescents and Young Adults.
AB  - The body mass index (BMI) is unsatisfactory in being affected by both relative
      leg length and height, and, for use with children and adolescents, therefore
      needs to be interpreted in relation to age. The sitting-height index of build
      (body mass)/(sitting height)3, is largely free of these disadvantages.
      Furthermore, because that index is independent of relative leg length, the latter
      can be treated as a separate indicator of nutritional history and health risks.
      Past studies on white children and adults have shown body mass to be
      approximately proportional to (sitting height)3. Moreover, multiple regression of
      (body mass)1/3 on sitting height and leg length, using year-by-year averages, has
      indicated that leg length is an insignificant predictor of body mass. The present
      study used data for individuals, namely 2-20 years old males and females, black
      as well as white. Regression analysis as above again showed leg length to be an
      insignificant predictor of body mass, but only above the age of about nine years.
      However, sitting height is still a stronger predictor of body mass than leg
      length at all ages. The advantages of the sitting-height index of build for use
      with young people are confirmed.

PMID- 29470415
TI  - Exclusive Breastfeeding Rate and Complementary Feeding Indicators in China: A
      National Representative Survey in 2013.
AB  - Appropriate infant and young child feeding could reduce morbidity and mortality
      and could improve cognitive development of children. However, nationwide data on
      exclusive breastfeeding and complementary feeding status in China are scarce. The
      aim of this study was to assess current exclusive breastfeeding and complementary
      feeding status in China. A national representative survey (Chinese National
      Nutrition and Health Survey) of children aged under 6 years was done in 2013.
      Stratified multistage cluster sampling was used to select study participants.
      World Health Organization (WHO) infant and young child feeding indicators were
      firstly used to assess exclusive breastfeeding and complementary feeding practice
      nationwide. In total, 14,458 children aged under two years (0 to <730 days) were
      studied from 55 counties in 30 provinces in China. The crude exclusive
      breastfeeding rate under 6 months was 20.7% (908/4381) and the weighted exclusive
      breastfeeding rate was 18.6%. The crude prevalence of minimum dietary diversity,
      minimum meal frequency and minimum acceptable diet were 52.5% (5286/10,071),
      69.8% (7027/10,071), and 27.4% (2764/10,071) among children aged 6-23 months,
      respectively. The weighted rate was 53.7%, 69.1%, and 25.1%, respectively.
      Residential area, household income and maternal education were positively
      associated with the three complementary feeding indicators. The exclusive
      breastfeeding rate under 6 months was low and complementary feeding practice was
      not optimal in China. Residential area, household income and maternal education
      might be used to target infants and young children to improve complementary
      feeding practice.

PMID- 29470416
TI  - Carbon-Fibre-Reinforced SiC Composite (C/SiSiC) as an Alternative Material for
      Endoprosthesis: Fabrication, Mechanical and In-Vitro Biological Properties.
AB  - Particle-induced periprosthetic osteolysis and subsequent aseptic implant
      loosening are a major cause of compromising the long-term results of total joint
      replacements. To date, no implant has been able to mirror radically the
      tribological factors (friction/lubrication/wear) of in vivo tribological
      pairings. Carbon-Fibre Reinforced SiC-Composites (C/SiSiC), a material primarily
      developed for brake technology, has the opportunity to fulfil this requirement.
      Until now, the material itself has not been used in medicine. The aim of this
      investigation was to test the suitability of C/SiSiC ceramics as a new material
      for bearing couples in endoprosthetics. After the preparation of the composites
      flexural strength was determined as well as the Young's-modulus and the
      coefficient of friction. To investigate in vitro biological properties, MG 63 and
      primary human osteoblasts were cultured on C/SiSiC composites. To review the
      proliferation, the cytotoxicity standardized tests were used. The cell morphology
      was observed by light microscopy, ESEM, confocal and 3D-laserscanning microscopy.
      C/SiSiC possesses a high resistance to wear. Cells exhibited no significant
      alterations in morphology. Vitality was not impaired by contact with the ceramic
      composite. There was no higher cytotoxicity to observe. Regarding these results,
      C/SiSiC ceramics seem to be biologically and mechanically appropriate for
      orthopaedic applications.

PMID- 29470417
TI  - Ultrarapid Multimode Microwave Synthesis of Nano/Submicron beta-SiC.
AB  - This paper presents the design, development and realization of a fast and novel
      process for the synthesis of 3C silicon carbide (beta-SiC) nanorods and submicron
      powder. Using SiO2 (or Si) and activated carbon (AC), this process allows beta
      SiC to be synthesized with almost 100% purity in timeframes of seconds or minutes
      using multimode microwave rotary tube reactors under open-air conditions. The
      synthesis temperature used was 1460 +/- 50  degrees C for Si + AC and 1660 +/- 50
      degrees C for SiO2 + AC. The shortest beta-SiC synthesis time achieved was about
      20 s for Si + AC and 100 s for SiO2 + AC. This novel synthesis method allows for
      scaled-up flow processes in the rapid industrial-scale production of beta-SiC,
      having advantages of time/energy saving and carbon dioxide emission reduction
      over comparable modern processes.

PMID- 29470418
TI  - Tetrodotoxin, a Candidate Drug for Nav1.1-Induced Mechanical Pain?
AB  - Tetrodotoxin (TTX), the mode of action of which has been known since the 1960s,
      is widely used in pharmacology as a specific inhibitor of voltage-gated sodium
      channels (Nav channels). This toxin has contributed to the characterization of
      the allosteric model of the Nav channel, and to discriminating TTX-sensitive and
      TTX-resistant subtypes. In addition to its role as a pharmacological tool, TTX is
      now considered a therapeutic molecule, and its development should lead to its use
      in certain pathologies involving Nav channels, particularly in the field of pain.
      Specifically, the blockade of Nav channels expressed in nociceptive fibres is one
      strategy for alleviating pain and its deleterious consequences on health. Recent
      work has identified, in addition to the Nav1.7, 1.8 and 1.9 channels, the Nav1.1
      subtype on dorsal root ganglion (DRG) neurons as a crucial player in mechanical
      and non-thermal pain. The sensitivity of Nav1.1 to TTX could be exploited at the
      therapeutic level, especially in chronic pain conditions.

PMID- 29470419
TI  - Nanotherapy and Reactive Oxygen Species (ROS) in Cancer: A Novel Perspective.
AB  - The incidence of numerous types of cancer has been increasing over recent years,
      representing the second-most frequent cause of death after cardiovascular
      diseases. Even though, the number of effective anticancer drugs is increasing as
      well, a large number of patients suffer from severe side effects (e.g.,
      cardiomyopathies) caused by these drugs. This adversely affects the patients'
      well-being and quality of life. On the molecular level, tumor cells that survive
      treatment modalities can become chemotherapy-resistant. In addition, adverse
      impacts on normal (healthy, stromal) cells occur concomitantly. Strategies that
      minimize these negative impacts on normal cells and which at the same time target
      tumor cells efficiently are needed. Recent studies suggest that redox-based
      combinational nanotherapies may represent one option in this direction. Here, we
      discuss recent advances in the application of nanoparticles, alone or in
      combination with other drugs, as a promising anticancer tool. Such novel
      strategies could well minimize harmful side effects and improve patients' health
      prognoses.

PMID- 29470420
TI  - Enhanced Antitumor Effects of Epidermal Growth Factor Receptor Targetable
      Cetuximab-Conjugated Polymeric Micelles for Photodynamic Therapy.
AB  - Nanocarrier-based delivery systems are promising strategies for enhanced
      therapeutic efficacy and safety of toxic drugs. Photodynamic therapy (PDT)-a
      light-triggered chemical reaction that generates localized tissue damage for
      disease treatments-usually has side effects, and thus patients receiving
      photosensitizers should be kept away from direct light to avoid skin
      phototoxicity. In this study, a clinically therapeutic antibody cetuximab (C225)
      was conjugated to the surface of methoxy poly(ethylene glycol)-b-poly(lactide)
      (mPEG-b-PLA) micelles via thiol-maleimide coupling to allow tumor-targetable
      chlorin e6 (Ce6) delivery. Our results demonstrate that more C225-conjugated Ce6
      loaded polymeric micelles (C225-Ce6/PM) were selectively taken up than Ce6/PM or
      IgG conjugated Ce6/PM by epidermal growth factor receptor (EGFR)-overexpressing
      A431 cells observed by confocal laser scanning microscopy (CLSM), thereby
      decreasing the IC50 value of Ce6-mediated PDT from 0.42 to 0.173 MUM. No
      significant differences were observed in cellular uptake study or IC50 value
      between C225-Ce6/PM and Ce6/PM groups in lower EGFR expression HT-29 cells. For
      antitumor study, the tumor volumes in the C225-Ce6/PM-PDT group (percentage of
      tumor growth inhibition, TGI% = 84.8) were significantly smaller than those in
      the Ce6-PDT (TGI% = 38.4) and Ce6/PM-PDT groups (TGI% = 53.3) (p < 0.05) at day
      21 through reduced cell proliferation in A431 xenografted mice. These results
      indicated that active EGFR targeting of photosensitizer-loaded micelles provides
      a possible way to resolve the dose-limiting toxicity of conventional
      photosensitizers and represents a potential delivery system for PDT in a clinical
      setting.

PMID- 29470421
TI  - Phytochemicals in Human Milk and Their Potential Antioxidative Protection.
AB  - Diets contain secondary plant metabolites commonly referred to as phytochemicals.
      Many of them are believed to impact human health through various mechanisms,
      including protection against oxidative stress and inflammation, and decreased
      risks of developing chronic diseases. For mothers and other people, phytochemical
      intake occurs through the consumption of foods such as fruits, vegetables, and
      grains. Research has shown that some these phytochemicals are present in the
      mother's milk and can contribute to its oxidative stability. For infants, human
      milk (HM) represents the primary and preferred source of nutrition because it is
      a complete food. Studies have reported that the benefit provided by HM goes
      beyond basic nutrition. It can, for example, reduce oxidative stress in infants,
      thereby reducing the risk of lung and intestinal diseases in infants. This paper
      summarizes the phytochemicals present in HM and their potential contribution to
      infant health.

PMID- 29470422
TI  - Fragment-Based Discovery of Inhibitors of the Bacterial DnaG-SSB Interaction.
AB  - In bacteria, the DnaG primase is responsible for synthesis of short RNA primers
      used to initiate chain extension by replicative DNA polymerase(s) during
      chromosomal replication. Among the proteins with which Escherichia coli DnaG
      interacts is the single-stranded DNA-binding protein, SSB. The C-terminal
      hexapeptide motif of SSB (DDDIPF; SSB-Ct) is highly conserved and is known to
      engage in essential interactions with many proteins in nucleic acid metabolism,
      including primase. Here, fragment-based screening by saturation-transfer
      difference nuclear magnetic resonance (STD-NMR) and surface plasmon resonance
      assays identified inhibitors of the primase/SSB-Ct interaction. Hits were shown
      to bind to the SSB-Ct-binding site using 15N-1H HSQC spectra. STD-NMR was used to
      demonstrate binding of one hit to other SSB-Ct binding partners, confirming the
      possibility of simultaneous inhibition of multiple protein/SSB interactions. The
      fragment molecules represent promising scaffolds on which to build to discover
      new antibacterial compounds.

PMID- 29470423
TI  - 3,5,6,7,8,3',4'-Heptamethoxyflavone, a Citrus Flavonoid, Inhibits Collagenase
      Activity and Induces Type I Procollagen Synthesis in HDFn Cells.
AB  - Citrus fruits contain various types of flavonoids with powerful anti-aging and
      photoprotective effects on the skin, and have thus been attracting attention as
      potential, efficacious skincare agents. Here, we aimed to investigate the
      chemical composition of Citrus unshiu and its protective effects on photoaging.
      We isolated and identified a bioactive compound, 3,5,6,7,8,3',4'
      heptamethoxyflavone (HMF), from C. unshiu peels using ethanol extraction and
      hexane fractionation. HMF inhibited collagenase activity and increased type I
      procollagen content in UV-induced human dermal fibroblast neonatal (HDFn) cells.
      HMF also suppressed the expression of matrix metalloproteinases 1 (MMP-1) and
      induced the expression of type I procollagen protein in UV-induced HDFn cells.
      Additionally, HMF inhibited ultraviolet B (UVB)-induced phosphorylation of the
      mitogen-activated protein kinases (MAPK) cascade signaling components-ERK, JNK,
      and c-Jun-which are involved in the induction of MMP-1 expression. Furthermore,
      HMF affected the TGF-beta/Smad signaling pathway, which is involved in the
      regulation of type I procollagen expression. In particular, HMF induced Smad3
      protein expression and suppressed Smad7 protein expression in UV-induced HDFn
      cells in a dose-dependent manner. These findings suggest a role for Citrusunshiu
      in the preparation of skincare products in future.

PMID- 29470424
TI  - Young Women's Perspectives of Their Adolescent Treatment Programs: A Qualitative
      Study.
AB  - The perspectives of at-risk adolescent clients can play an important role in
      informing treatment services. The current study examines qualitative interview
      data from 15 young women with histories of maltreatment. Using a semi-structured
      qualitative interview approach, we asked the women to think retrospectively about
      their treatment experiences as adolescent girls. Results highlight the need for
      providing adolescent girls with reliable and practical information about risky
      sexual behavior and drug use from relatable and trustworthy helping
      professionals. We discuss strategies for developing and maintaining trust and
      delivering specific content.

PMID- 29470427
TI  - Application of Ground-Penetrating Radar for Detecting Internal Anomalies in Tree
      Trunks with Irregular Contours.
AB  - To assess the health conditions of tree trunks, it is necessary to estimate the
      layers and anomalies of their internal structure. The main objective of this
      paper is to investigate the internal part of tree trunks considering their
      irregular contour. In this respect, we used ground penetrating radar (GPR) for
      non-invasive detection of defects and deteriorations in living trees trunks. The
      Hilbert transform algorithm and the reflection amplitudes were used to estimate
      the relative dielectric constant. The point cloud data technique was applied as
      well to extract the irregular contours of trunks. The feasibility and accuracy of
      the methods were examined through numerical simulations, laboratory and field
      measurements. The results demonstrated that the applied methodology allowed for
      accurate characterizations of the internal inhomogeneity. Furthermore, the point
      cloud technique resolved the trunk well by providing high-precision coordinate
      information. This study also demonstrated that cross-section tomography provided
      images with high resolution and accuracy. These integrated techniques thus proved
      to be promising for observing tree trunks and other cylindrical objects. The
      applied approaches offer a great promise for future 3D reconstruction of
      tomographic images with radar wave.

PMID- 29470426
TI  - Surface Plasmon Resonance and Bending Loss-Based U-Shaped Plastic Optical Fiber
      Biosensors.
AB  - Escherichia coli (E. coli) is a large and diverse bacteria group that inhabits
      the intestinal tract of many mammals. Most E. coli strains are harmless, however
      some of them are pathogenic, meaning they can make one sick if ingested. By being
      in the feces of animals and humans, its presence in water and food is used as
      indicator of fecal contamination. The main method for this microorganism
      detection is the bacterial culture medium that is time-consuming and requires a
      laboratory with specialized personnel. Other sophisticated methods are still not
      fast enough because they require sending samples to a laboratory and with a high
      cost of analysis. In this paper, a gold-coated U-shaped plastic optical fiber
      (POF) biosensor for E. coli bacteria detection is presented. The biosensor works
      by intensity modulation principle excited by monochromatic light where the power
      absorption is imposed by predominant effect of either bending loss or surface
      plasmon resonance (SPR), depending on the gold thickness. Bacterial selectivity
      is obtained by antibody immobilization on the fiber surface. The biosensor showed
      a detection limit of 1.5 * 103 colony-forming units (CFU)/mL, demonstrating that
      the technology can be a portable, fast response and low-cost alternative to
      conventional methodologies for quality analysis of water and food.

PMID- 29470425
TI  - Major Histocompatibility Complex and Hematopoietic Stem Cell Transplantation:
      Beyond the Classical HLA Polymorphism.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) represents a curative
      treatment for many patients with hematological malignant or non-malignant
      disorders. Evaluation of potential donors for HSCT includes a rigorous assessment
      of the human leukocyte antigens (HLA) match status of family members, and the
      identification of suitable unrelated donors. Genes encoding transplantation
      antigens are placed both within and outside the major histocompatibility complex
      (MHC). The human MHC is located on the short arm of chromosome 6 and contains a
      series of genes encoding two distinct types of highly polymorphic cell surface
      glycoproteins. Donors for HSCT are routinely selected based on the level of
      matching for HLA-A, -B, -C, -DRB1, and -DQB1 loci. However, disease relapse,
      graft-versus-host-disease, and infection remain significant risk factors of
      morbidity and mortality. In the same breath, in high-risk patients, graft-versus
      leukemia effects inherent in HLA mismatching play a substantial immunological
      role to limit the recurrence of post-transplant disease. The definition of a
      suitable donor is ever changing, shaped not only by current typing technology,
      but also by the specific transplant procedure. Indeed, a more complete
      understanding of permissible HLA mismatches and the role of Killer Immunoglobulin
      like receptors' genes increases the availability of HLA-haploidentical and
      unrelated donors.

PMID- 29470428
TI  - Determining Forest Duff Water Content Using a Low-Cost Standing Wave Ratio
      Sensor.
AB  - Forest duff (fermentation and humus) water content is an important parameter for
      fire risk prediction and water resource management. However, accurate
      determination of forest duff water content is difficult due to its loose
      structure. This study evaluates the feasibility of a standing wave ratio (SWR)
      sensor to accurately determine the forest duff water content. The performance of
      this sensor was tested on fermentation and humus with eight different compaction
      levels. Meanwhile, a commercialized time domain reflectometry (TDR) was employed
      for comparison. Calibration results showed that there were strong linear
      relationships between the volumetric water content (thetaV) and the SWR sensor
      readings (VSWR) at different compaction classes for both fermentation and humus
      samples. The sensor readings of both SWR and TDR underestimated the forest duff
      water content at low compacted levels, proving that the compaction of forest duff
      could significantly affect the measurement accuracy of both sensors. Experimental
      data also showed that the accuracy of the SWR sensor was higher than that of TDR
      according to the root mean square error (RMSE). Furthermore, low cost is another
      important advantage of the SWR sensor in comparison with TDR. This low-cost SWR
      sensor performs well in loose materials and is feasible for evaluating the water
      content of forest duff. In addition, the results indicate that decomposition of
      the forest duff should be taken into account for continuous and long-term water
      content measurement.

PMID- 29470429
TI  - Belowground Interactions Impact the Soil Bacterial Community, Soil Fertility, and
      Crop Yield in Maize/Peanut Intercropping Systems.
AB  - Intercropping has been widely used to control disease and improve yield in
      agriculture. In this study, maize and peanut were used for non-separation
      intercropping (NS), semi-separation intercropping (SS) using a nylon net, and
      complete separation intercropping (CS) using a plastic sheet. In field
      experiments, two-year land equivalent ratios (LERs) showed yield advantages due
      to belowground interactions when using NS and SS patterns as compared to
      monoculture. In contrast, intercropping without belowground interactions (CS)
      showed a yield disadvantage. Meanwhile, in pot experiments, belowground
      interactions (found in NS and SS) improved levels of soil-available nutrients
      (nitrogen (N) and phosphorus (P)) and enzymes (urease and acid
      phosphomonoesterase) as compared to intercropping without belowground
      interactions (CS). Soil bacterial community assay showed that soil bacterial
      communities in the NS and SS crops clustered together and were considerably
      different from the CS crops. The diversity of bacterial communities was
      significantly improved in soils with NS and SS. The abundance of beneficial
      bacteria, which have the functions of P-solubilization, pathogen suppression, and
      N-cycling, was improved in maize and peanut soils due to belowground interactions
      through intercropping. Among these bacteria, numbers of Bacillus,
      Brevibacillusbrevis, and Paenibacillus were mainly increased in the maize
      rhizosphere. Burkholderia, Pseudomonas, and Rhizobium were mainly increased in
      the peanut rhizosphere. In conclusion, using maize and peanut intercropping,
      belowground interactions increased the numbers of beneficial bacteria in the soil
      and improved the diversity of the bacterial community, which was conducive to
      improving soil nutrient (N and P) supply capacity and soil microecosystem
      stability.

PMID- 29470430
TI  - Metabolic Responses in Endothelial Cells Following Exposure to Ketone Bodies.
AB  - The ketogenic diet (KD) is a high-fat, low-carbohydrate diet based on the
      induction of the synthesis of ketone bodies (KB). Despite its widespread use, the
      systemic impact of KD is not completely understood. The purpose of this study was
      to evaluate the effects of physiological levels of KB on HMEC-1 endothelial
      cells. To this aim, DNA oxidative damage and the activation of Nrf2, a known
      transcriptional factor involved in cell responses to oxidative stress, were
      assessed. The exposure of cells to KB exerted a moderate genotoxic effect,
      measured by a significant increase in DNA oxidative damage. However, cells pre
      treated with KB for 48 h and subjected to a secondary oxidative insult (H2O2),
      significantly decreased DNA damage compared to control oxidized cells. This
      protection occurred by the activation of Nrf2 pathway. In KB-treated cells, we
      found increased levels of Nrf2 in nuclear extracts and higher gene expression of
      HO-1, a target gene of Nrf2, compared to control cells. These results suggest
      that KB, by inducing moderate oxidative stress, activate the transcription factor
      Nrf2, which induces the transcription of target genes involved in the cellular
      antioxidant defense system.

PMID- 29470432
TI  - Optical Method for Estimating the Chlorophyll Contents in Plant Leaves.
AB  - This work introduces a new vision-based approach for estimating chlorophyll
      contents in a plant leaf using reflectance and transmittance as base parameters.
      Images of the top and underside of the leaf are captured. To estimate the base
      parameters (reflectance/transmittance), a novel optical arrangement is proposed.
      The chlorophyll content is then estimated by using linear regression where the
      inputs are the reflectance and transmittance of the leaf. Performance of the
      proposed method for chlorophyll content estimation was compared with a
      spectrophotometer and a Soil Plant Analysis Development (SPAD) meter. Chlorophyll
      content estimation was realized for Lactuca sativa L., Azadirachta indica,
      Canavalia ensiforme, and Lycopersicon esculentum. Experimental results showed
      that-in terms of accuracy and processing speed-the proposed algorithm
      outperformed many of the previous vision-based approach methods that have used
      SPAD as a reference device. On the other hand, the accuracy reached is 91% for
      crops such as Azadirachta indica, where the chlorophyll value was obtained using
      the spectrophotometer. Additionally, it was possible to achieve an estimation of
      the chlorophyll content in the leaf every 200 ms with a low-cost camera and a
      simple optical arrangement. This non-destructive method increased accuracy in the
      chlorophyll content estimation by using an optical arrangement that yielded both
      the reflectance and transmittance information, while the required hardware is
      cheap.

PMID- 29470431
TI  - Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation
      and Stem Cell Therapy.
AB  - Changes in articular cartilage during the aging process are a stage of natural
      changes in the human body. Old age is the major risk factor for osteoarthritis
      but the disease does not have to be an inevitable consequence of aging.
      Chondrocytes are particularly prone to developing age-related changes. Changes in
      articular cartilage that take place in the course of aging include the
      acquisition of the senescence-associated secretory phenotype by chondrocytes, a
      decrease in the sensitivity of chondrocytes to growth factors, a destructive
      effect of chronic production of reactive oxygen species and the accumulation of
      the glycation end products. All of these factors affect the mechanical properties
      of articular cartilage. A better understanding of the underlying mechanisms in
      the process of articular cartilage aging may help to create new therapies aimed
      at slowing or inhibiting age-related modifications of articular cartilage. This
      paper presents the causes and consequences of cellular aging of chondrocytes and
      the biological therapeutic outlook for the regeneration of age-related changes of
      articular cartilage.

PMID- 29470433
TI  - Monitoring Heavy Metal Contents with Sphagnum Junghuhnianum Moss Bags in Relation
      to Traffic Volume in Wuxi, China.
AB  - Despite its small size, a moss bag can reveal the different temporal and spatial
      deposition patterns of pollutants at a particular site; therefore, researchers
      can use moss bags to determine pollution sources and to put forward strategies
      for pollution control. Although the use of moss bags to monitor atmospheric
      pollution has been widely reported in Europe, there are few such empirical
      studies in China. Thus, in this study, bags containing the moss Sphagnum
      junghuhnianum were used to assess the concentrations of heavy metals (chromium
      (Cr), copper (Cu), lead (Pb), vanadium (V), and zinc (Zn)) at five sampling sites
      (four roads and a forest park) during the summer and winter of 2012. According to
      the relative accumulation factor (RAF) and contamination factor (CF) results,
      pollution in winter was heavier than that in summer, and Cr was found to be the
      most contaminating, having the highest mean CF. There was a significant positive
      correlation (p < 0.05) between traffic volume and concentration for three heavy
      metals (Cr, Cu, and V) in winter, whereas a significant positive correlation (p <
      0.05) was observed between traffic volume and concentrations for four heavy metal
      elements (Cr, Pb, V, and Zn) in summer, indicating a close relationship between
      heavy metal contents and traffic volume. Although there was substantial variation
      in the concentrations of the five heavy metals in the moss bags, significant
      correlations between heavy metals suggested that the contaminants originated from
      a common source, namely vehicle emissions. The results demonstrated that the four
      roads were subject to different degrees of pollution depending on the volume of
      traffic using each road. Therefore, the results of this study suggest that
      traffic volume is a major reason for heavy metal pollution.

PMID- 29470434
TI  - Pharmacokinetics and Scintigraphic Imaging of the Hypoxia-Imaging Agent
      [123I]IAZA in Healthy Adults Following Exercise-Based Cardiac Stress ?.
AB  - The objective of this work is to evaluate the potential effect of cardiac stress
      exercise on the accumulation of [123I]IAZA, a radiopharmaceutical used to image
      focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and
      to determine the impact of exercise on [123I]IAZA pharmacokinetics. The
      underlying goal is to establish a rational basis and a baseline for studies of
      focal myocardial hypoxia in cardiac patients using [123I]IAZA. Three healthy male
      volunteers ran the 'Bruce' treadmill protocol, a clinically-accepted protocol
      designed to expose myocardial ischemia in patients. The 'Bruce' criterion heart
      rate is 85% of [220-age]. Approximately one minute before reaching this level,
      [123I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1-3 min) single
      intravenous (i.v.) injection via an indwelling venous catheter. The volunteer
      continued running for an additional 1 min before being transferred to a gamma
      camera. Serum samples were collected from the arm contralateral to the
      administration site at pre-determined intervals from 1 min to 45 h post injection
      and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for
      [123I]IAZA and total radioactivity (total[123I]) using compartmental and
      noncompartmental analyses. Whole-body planar scintigraphic images were acquired
      from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to
      previously published [123I]IAZA data from healthy volunteers rest. Following
      exercise stress, both [123I]IAZA and total[123I] exhibited bi-exponential decline
      profiles, with rapid distribution phases [half-lives (t1/2alpha) of 1.2 and 1.4
      min, respectively], followed by slower elimination phases [t1/2beta of 195 and
      290 min, respectively]. Total body clearance (CLTB) and the steady state volume
      of distribution (Vss) were 0.647 L/kg and 185 mL/min, respectively, for
      [123I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[123I]. The
      t1/2beta, CLTB and Vss values were comparable to those reported previously for
      rested volunteers. The t1/2alpha was approximately 4-fold shorter for [123I]IAZA
      and approximately 3-fold shorter for total[123I] under exercise relative to
      rested subjects. The heart region was visualized in early whole body
      scintigraphic images, but later images showed no accumulated radioactivity in
      this region, and no differences from images reported for rested volunteers were
      apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was
      consistent with uptake in non-stressed myocardium. Whole-body scintigrams for
      [123I]IAZA in exercise-stressed healthy volunteers were indistinguishable from
      images of non-exercised volunteers. There was no evidence of hypoxia-dependent
      binding in exercised but otherwise healthy myocardium, supporting the conclusion
      that exercise stress at Bruce protocol intensity does not induce measurable
      myocardial hypoxia. Effects of exercise on PK parameters were minimal;
      specifically, the t1/2alpha was shortened, reflecting increased cardiac output
      associated with exercise. It is concluded that because [123I]IAZA was not
      metabolically bound in exercise-stressed myocardium, a stress test will not
      create elevated myocardial background that would mask regions of myocardial
      perfusion deficiency. [123I]IAZA would therefore be suitable for the detection of
      viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis.

PMID- 29470435
TI  - Creative Arts Interventions for Stress Management and Prevention-A Systematic
      Review.
AB  - Stress is one of the world's largest health problems, leading to exhaustion,
      burnout, anxiety, a weak immune system, or even organ damage. In Germany, stress
      induced work absenteeism costs about 20 billion Euros per year. Therefore, it is
      not surprising that the Central Federal Association of the public Health
      Insurance Funds in Germany ascribes particular importance to stress prevention
      and stress management as well as health enhancing measures. Building on current
      integrative and embodied stress theories, Creative Arts Therapies (CATs) or arts
      interventions are an innovative way to prevent stress and improve stress
      management. CATs encompass art, music, dance/movement, and drama therapy as their
      four major modalities. In order to obtain an overview of CATs and arts
      interventions' efficacy in the context of stress reduction and management, we
      conducted a systematic review with a search in the following data bases: Academic
      Search Complete, ERIC, Medline, Psyndex, PsycINFO and SocINDEX. Studies were
      included employing the PICOS principle and rated according to their evidence
      level. We included 37 studies, 73% of which were randomized controlled trials.
      81.1% of the included studies reported a significant reduction of stress in the
      participants due to interventions of one of the four arts modalities.

PMID- 29470436
TI  - Neurobiology of Propofol Addiction and Supportive Evidence: What Is the New
      Development?
AB  - Propofol is a short-acting intravenous anesthetic agent suitable for induction
      and maintenance of general anesthesia as well as for procedural and intensive
      care unit sedation. As such it has become an unparalleled anesthetic agent of
      choice in many institutional and office practices. However, in addition to its
      idealistic properties as an anesthetic agent, there is accumulating evidence
      suggesting its potential for abuse. Clinical and experimental evidence has
      revealed that not only does propofol have the potential to be abused, but also
      that addiction to propofol shows a high mortality rate. Based on this evidence,
      different researchers have shown interest in determining the probability of
      propofol to be an addictive agent by comparing it with other drugs of abuse and
      depicting a functional similitude that involves the mesocorticolimbic pathway of
      addiction. In light of this, the Drug Enforcement Agency and the American Society
      of Anesthesiologists have put forth certain safety recommendations for the use of
      propofol. Despite this, the abuse potential of propofol has been challenged at
      different levels and therefore the preeminent focus will be to further validate
      the linkage from medicinal and occasional use of propofol to its addiction, as
      well as to explore the cellular and molecular targets involved in establishing
      this linkage, so as to curb the harm arising out of it. This review incorporates
      the clinical and biomolecular evidence supporting the abuse potential of propofol
      and brings forth the promising targets and the foreseeable mechanism causing the
      propofol addiction phenotypes, which can be called upon for future developments
      in this field.

PMID- 29470437
TI  - Neurophysiological Assessment of Abnormalities of the Neuromuscular Junction in
      Children.
AB  - The function of the neuromuscular junction in children is amenable to
      electrophysiological testing. Of the two tests available, repetitive nerve
      stimulation is uncomfortable and has a reduced sensitivity compared with single
      fibre methodology. The latter is the method of choice, recording the variability
      in neuromuscular transmission as a value called jitter. It can be performed by
      voluntary activation of the muscle being examined, which is not suitable in
      children, or by stimulation techniques. A modification of these techniques,
      called Stimulated Potential Analysis with Concentric needle Electrodes (SPACE),
      is well tolerated and can be performed while the child is awake. It has a high
      sensitivity (84%) for the diagnosis of neuromuscular transmission disorders, the
      majority of which are myasthenic syndromes, and a moderate specificity (70%). The
      latter can be improved by the exclusion of neurogenic causes and the
      determination of the degree of jitter abnormality. Minor jitter abnormalities,
      under 115% of the upper limit of normal, are usually caused by myopathies with an
      associated neuromuscular transmission disorder, whereas levels higher than this
      value are usually associated with one of the myasthenic conditions.

PMID- 29470439
TI  - Study of Hexane Adsorption on Activated Carbons with Differences in Their Surface
      Chemistry.
AB  - The study of aliphatic compounds adsorption on activated carbon can be carried
      out from the energetic change involved in the interaction; the energy values can
      be determined from isotherms or by the immersion enthalpy. Vapor phase adsorption
      isotherms of hexane at 263 K on five activated carbons with different content of
      oxygenated groups and the immersion enthalpy of the activated carbons in hexane
      and water were determined in order to characterize the interactions in the solid
      liquid system, and for calculating the hydrophobic factor of the activated
      carbons. The micropore volume and characteristic energy from adsorption isotherms
      of hexane, the BET (Brunauer-Emmett-Teller) surface area from the adsorption
      isotherms of N2, and the area accessible to the hexane from the immersion
      enthalpy were calculated. The activated carbon with the lowest content of
      oxygenated groups (0.30 umolg-1) and the highest surface area (996 m2g-1) had the
      highest hexane adsorption value: 0.27 mmol g-1; the values for Eo were between
      5650 and 6920 Jmol-1 and for DeltaHim were between -66.1 and -16.4 Jg-1. These
      determinations allow us to correlate energetic parameters with the surface area
      and the chemical modifications that were made to the solids, where the surface
      hydrophobic character of the activated carbon favors the interaction.

PMID- 29470438
TI  - Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside
      Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid
      Lipofuscinosis.
AB  - Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3
      gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and
      8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C
      terminus. A genetically accurate mouse model (Cln3Deltaex7/8 mice) for this
      deletion has been generated. Using cerebellar precursor cell lines generated from
      wildtype and Cln3Deltaex7/8 mice, we have here analyzed the consequences of the
      CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and
      GD1a. The levels of GM1a and GD1a were found to be significantly reduced by both
      biochemical and cytochemical methods. However, quantitative high-performance
      liquid chromatography analysis revealed a highly significant increase in GM3,
      suggesting a metabolic blockade in the conversion of GM3 to more complex
      gangliosides. Quantitative real-time PCR analysis revealed a significant
      reduction in the transcripts of the interconverting enzymes, especially of beta
      1,4-N-acetyl-galactosaminyl transferase 1 (GM2 synthase), which is the enzyme
      converting GM3 to GM2. Thus, our data suggest that the complex a-series
      gangliosides are reduced in Cln3Deltaex7/8 mouse cerebellar precursor cells due
      to impaired transcription of the genes responsible for their synthesis.

PMID- 29470440
TI  - Membranes: A Variety of Energy Landscapes for Many Transfer Opportunities.
AB  - A membrane can be represented by an energy landscape that solutes or colloids
      must cross. A model accounting for the momentum and the mass balances in the
      membrane energy landscape establishes a new way of writing for the Darcy law. The
      counter-pressure in the Darcy law is no longer written as the result of an
      osmotic pressure difference but rather as a function of colloid-membrane
      interactions. The ability of the model to describe the physics of the filtration
      is discussed in detail. This model is solved in a simplified energy landscape to
      derive analytical relationships that describe the selectivity and the counter
      pressure from ab initio operating conditions. The model shows that the stiffness
      of the energy landscape has an impact on the process efficiency: a gradual
      increase in interactions (such as with hourglass pore shape) can reduce the
      separation energetic cost. It allows the introduction of a new paradigm to
      increase membrane efficiency: the accumulation that is inherent to the separation
      must be distributed across the membrane. Asymmetric interactions thus lead to
      direction-dependent transfer properties and the membrane exhibits diode behavior.
      These new transfer opportunities are discussed.

PMID- 29470441
TI  - Effect of Silver-Emitting Filler on Antimicrobial and Mechanical Properties of
      Soft Denture Lining Material.
AB  - Colonization of silicone-based soft lining materials by pathogenic yeast-type
      fungi is a common problem associated with the use of dentures. In this study,
      silver sodium hydrogen zirconium phosphate (SSHZP) was introduced into
      polydimethylsiloxane-based material as an antimicrobial filler at concentrations
      of 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 14% (w/w). The in vitro antimicrobial
      efficacy was investigated. Candida albicans was used as a characteristic
      representative of pathogenic oral microflora. Staphylococcus aureus and
      Escherichia coli were used as the typical Gram-positive and Gram-negative
      bacterial strains, respectively. The effect of filler addition on the Shore A
      hardness, tensile strength, tensile bond strength, sorption, and solubility was
      investigated. An increase in the filler concentration resulted in an increase in
      hardness, sorption, and solubility, and for the highest concentration, a decrease
      in bond strength. The favorable combination of antimicrobial efficacy with other
      properties was achieved at filler concentrations ranging from 2% to 10%. These
      composites exhibited mechanical properties similar to the material without the
      antimicrobial filler and enhanced in vitro antimicrobial efficiency.

PMID- 29470442
TI  - Phycocyanin Protects Against UVB-induced Apoptosis Through the PKC alpha/betaII
      Nrf-2/HO-1 Dependent Pathway in Human Primary Skin Cells.
AB  - Phycocyanin (Pc) is one of the active pigment constituents of Spirulina
      microalgae. It has been used for its potent antioxidant and anti-inflammatory
      properties. However, the protective effects of Pc against ultraviolet-B (UVB)
      induced primary skin cells damage are still undefined. In the present study, we
      investigated whether Pc prevented UVB-induced apoptotic cell death in human
      dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK). Pc induced the
      transcription of heme oxygenase-1 (HO-1). Furthermore, Pc treatments resulted in
      a marked increase in nuclear factor erythroid-derived 2 (NF-E2)-like 2 (Nrf-2)
      nuclear translocation. Also, Pc protected UVB induced apoptosis and reduced the
      p53 and Bax levels, as well as caspase-3 activation. Pc treatment showed a
      significantly enhanced effect on the phosphorylation of protein kinase C (PKC)
      alpha/beta II, but not that of p38 mitogen-activated protein kinase (MAPK) or
      Akt. Induction of HO-1 induced by Pc was suppressed by Go6976, a selective
      inhibitor of PKC alpha/beta II. In addition, knockdown of HO-1 by small
      interfering (siRNA) caused a significant increase in poly (ADP-ribose) polymerase
      1 (PARP-1) cleavage and caspase-3 activation after Pc pretreatment. Taken
      together, our results demonstrate that Pc-induced expression of HO-1 is mediated
      by the PKC alpha/beta II-Nrf-2/HO-1 pathway, and inhibits UVB-induced apoptotic
      cell death in primary skin cells.

PMID- 29470443
TI  - Structure-Antiplatelet Activity Relationships of Novel Ruthenium (II) Complexes:
      Investigation of Its Molecular Targets.
AB  - The regulation of platelet function by pharmacological agents that modulate
      platelet signaling has proven to be a positive approach to the prevention of
      thrombosis. Ruthenium complexes are fascinating for the development of new drugs,
      as they possess numerous chemical and biological properties. The present study
      aims to evaluate the structure-activity relationship (SAR) of newly synthesized
      ruthenium (II) complexes, TQ-1, TQ-2 and TQ-3 in agonists-induced washed human
      platelets. Silica gel column chromatography, aggregometry, immunoblotting, NMR,
      and X-ray analyses were performed in this study. Of the three tested compounds,
      TQ-3 showed a concentration (1-5 MUM) dependent inhibitory effect on platelet
      aggregation induced by collagen (1 MUg/mL) and thrombin (0.01 U/mL) in washed
      human platelets; however, TQ-1 and TQ-2 had no response even at 250 MUM of
      collagen and thrombin-induced aggregation. TQ-3 was effective with inhibiting
      collagen-induced ATP release, calcium mobilization ([Ca2+]i) and P-selectin
      expression without cytotoxicity. Moreover, TQ-3 significantly abolished collagen
      induced Lyn-Fyn-Syk, Akt-JNK and p38 mitogen-activated protein kinases (p38
      MAPKs) phosphorylation. The compound TQ-3 containing an electron donating amino
      group with two phenyl groups of the quinoline core could be accounted for by its
      hydrophobicity and this nature might be the reason for the noted antiplatelet
      effects of TQ-3. The present results provide a molecular basis for the inhibition
      by TQ-3 in collagen-induced platelet aggregation, through the suppression of
      multiple machineries of the signaling pathway. These results may suggest that TQ
      3 can be considered a potential agent for the treatment of vascular diseases.

PMID- 29470444
TI  - Identification and Evaluation of Cytotoxicity of Peptide Liposome Incorporated
      Citron Extracts in an in Vitro System.
AB  - Abstract: Citrons have been widely used for medicinal purposes for a long time,
      but the application of citron in the food industry is still restricted. The
      extensive advantages of nanotechnology in the food industry have greatly
      broadened the application of foods. In this study, by employing nanotechnology,
      we prepared citron-extract nanoparticle with an average size of 174.11 +/- 3.89
      nm, containing protein peptide and/or liposome. In order to evaluate the toxicity
      of nanoparticles and to ensure food safety, biological cytotoxicity at the cell
      and genomic levels was also identified to examine the toxicity of citron extracts
      by using an in vitro system. Our results demonstrated that the cytotoxicity of
      citronliposome was dependent on cell type in high concentrations (1 and 5 mg/mL),
      selectively against primary human cardiac progenitor cells (hCPCs), and human
      endothelial progenitor cells (hEPCs) in MTT and lactate dehydrogenase (LDH)
      assays. Interestingly, for the NIH-3T3 and H9C2 cell lines, cell cytotoxicity was
      observed with slight genotoxicity, especially from citronpeptide extract for both
      cell lines. Taken together, our study provides cytotoxicity data on
      nanoengineered citron extracts according to different cell type as is crucial for
      further applications.

PMID- 29470446
TI  - A Cross-Layer, Anomaly-Based IDS for WSN and MANET.
AB  - Intrusion detection system (IDS) design for mobile adhoc networks (MANET) is a
      crucial component for maintaining the integrity of the network. The need for
      rapid deployment of IDS capability with minimal data availability for training
      and testing is an important requirement of such systems, especially for MANETs
      deployed in highly dynamic scenarios, such as battlefields. This work proposes a
      two-level detection scheme for detecting malicious nodes in MANETs. The first
      level deploys dedicated sniffers working in promiscuous mode. Each sniffer
      utilizes a decision-tree-based classifier that generates quantities which we
      refer to as correctly classified instances (CCIs) every reporting time. In the
      second level, the CCIs are sent to an algorithmically run supernode that
      calculates quantities, which we refer to as the accumulated measure of
      fluctuation (AMoF) of the received CCIs for each node under test (NUT). A key
      concept that is used in this work is that the variability of the smaller size
      population which represents the number of malicious nodes in the network is
      greater than the variance of the larger size population which represents the
      number of normal nodes in the network. A linear regression process is then
      performed in parallel with the calculation of the AMoF for fitting purposes and
      to set a proper threshold based on the slope of the fitted lines. As a result,
      the malicious nodes are efficiently and effectively separated from the normal
      nodes. The proposed scheme is tested for various node velocities and power levels
      and shows promising detection performance even at low-power levels. The results
      presented also apply to wireless sensor networks (WSN) and represent a novel IDS
      scheme for such networks.

PMID- 29470445
TI  - Recognition of AMP, ADP and ATP through Cooperative Binding by Cu(II) and Zn(II)
      Complexes Containing Urea and/or Phenylboronic-Acid Moieties.
AB  - We report a series of Cu(II) and Zn(II) complexes with different ligands
      containing a dipicolyl unit functionalized with urea groups that may contain or
      not a phenylboronic acid function. These complexes were designed for the
      recognition of phosphorylated anions through coordination to the metal ion
      reinforced by hydrogen bonds involving the anion and NH groups of urea. The
      complexes were isolated and several adducts with pyrophosphate were characterized
      using Xray diffraction measurements. Coordination of one of the urea nitrogen
      atoms to the metal ion promoted the hydrolysis of the ligands containing 1,3
      diphenylurea units, while ligands bearing 1-ethyl-3-phenylurea groups did not
      hydrolyze significantly at room temperature. Spectrophotometric titrations,
      combined with 1H and 31P NMR studies, were used in investigating the binding of
      phosphate, pyrophosphate (PPi), and nucleoside 5'-polyphosphates (AMP, ADP, ATP,
      CMP, and UMP). The association constants determined in aqueous solution (pH 7.0,
      0.1 M MOPS) point to a stronger association with PPi, ADP, and ATP as compared
      with the anions containing a single phosphate unit. The [CuL4]2+ complex shows
      important selectivity for pyrophosphate (PPi) over ADP and ATP.

PMID- 29470448
TI  - The Spectrum Analysis Solution (SAS) System: Theoretical Analysis, Hardware
      Design and Implementation.
AB  - This paper describes a multichannel super-heterodyne signal analyzer, called the
      Spectrum Analysis Solution (SAS), which performs multi-purpose spectrum sensing
      to support spectrally adaptive and cognitive radar applications. The SAS operates
      from ultrahigh frequency (UHF) to the S-band and features a wideband channel with
      eight narrowband channels. The wideband channel acts as a monitoring channel that
      can be used to tune the instantaneous band of the narrowband channels to areas of
      interest in the spectrum. The data collected from the SAS has been utilized to
      develop spectrum sensing algorithms for the budding field of spectrum sharing
      (SS) radar. Bandwidth (BW), average total power, percent occupancy (PO), signal
      to-interference-plus-noise ratio (SINR), and power spectral entropy (PSE) have
      been examined as metrics for the characterization of the spectrum. These metrics
      are utilized to determine a contiguous optimal sub-band (OSB) for a SS radar
      transmission in a given spectrum for different modalities. Three OSB algorithms
      are presented and evaluated: the spectrum sensing multi objective (SS-MO), the
      spectrum sensing with brute force PSE (SS-BFE), and the spectrum sensing multi
      objective with brute force PSE (SS-MO-BFE).

PMID- 29470447
TI  - Empirical Examinations of Effects of Three-Level Green Exercise on Engagement
      with Nature and Physical Activity.
AB  - Green exercise can be classified into three levels based on engagement with
      nature. Although this classification was proposed more than a decade ago, few
      studies have investigated it since. The present study examined the effects of
      green exercise levels on engagement with nature and physical activity (PA)
      through a field experiment. A questionnaire was distributed to 95 students from a
      technology university in Central Taiwan to measure their level of engagement with
      nature in people-environment transactions, while their PA was measured using
      three instruments. In addition, because social interaction may distract
      individual attention from activities or their environments, the present study
      incorporated the presence of partners as a control variable. The results revealed
      that (1) engagement with nature and PA significantly differed between the levels
      of green exercise, and the higher the level of green exercise participated in,
      the greater the level of engagement with nature; and (2) although the presence of
      partners did not influence the level of engagement with nature, it significantly
      affected the level of PA.

PMID- 29470449
TI  - Determinants of Quality of Life and Satisfaction with Life in Women with
      Polycystic Ovary Syndrome.
AB  - The purpose of the study was to assess the quality of life (QoL) and satisfaction
      with life (SwL) of women with polycystic ovary syndrome (PCOS) in comparison with
      those of healthy controls, and to identify and analyze factors determining QoL
      and SwL in women with PCOS. The cross-sectional study was performed between
      January and November 2016 in 504 women using health care services in Poland. The
      study group comprised women with PCOS, the control group women without PCOS. The
      study used a diagnostic survey with questionnaires. Research instruments included
      the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire,
      the satisfaction with life scale (SWLS), and a standardized interview
      questionnaire comprising questions on the participants' characteristics. Women
      with PCOS have lower QoL and SwL than healthy controls (p < 0.05). Factors
      affecting QoL in PCOS patients included socio-economic standing, time from PCOS
      diagnosis, BMI, age, and professional activity (p < 0.05). Factors affecting SwL
      in PCOS patients included socio-economic standing, having children, BMI, and time
      from PCOS diagnosis (p < 0.05). The higher the PCOS patients' QoL, the higher
      their SwL (p < 0.05). Further studies are required, focusing both on PCOS and its
      etiology, and on its impact on the women diagnosed with the disease.

PMID- 29470450
TI  - Exploring the Barriers: A Qualitative Study about the Experiences of Mid-SES Roma
      Navigating the Spanish Healthcare System.
AB  - Whereas the topic of the 'cultural sensitivity' of healthcare systems has been
      addressed extensively in the US and the UK, literature on the subject in most
      European countries, specifically looking at the situation of Roma, is still
      scarce. Drawing on qualitative research conducted mainly in the city of Barcelona
      under the communicative approach with Roma subjects who have stable socioeconomic
      positions and higher cultural capitals (end-users, professionals of the
      healthcare system, and key informants of a regional policy oriented to the
      improvement of Roma living conditions), the present study aims to fill this gap.
      We explore the barriers that the Roma face in accessing the healthcare system,
      reflecting on how these barriers are accentuated by the existing anti-Roma
      prejudices and institutional arrangements that do not account for minority
      cultures. Our results point out a series of obstacles at two levels, in the
      interaction with healthcare professionals, and in relation to existing
      institutional arrangements, which prevent Roma families from having equal access
      to the healthcare system. Education stands up as a mechanism to contest anti-Roma
      sentiments among healthcare professionals.

PMID- 29470451
TI  - The Impacts of Regulations and Financial Development on the Operations of Supply
      Chains with Greenhouse Gas Emissions.
AB  - To establish a micro foundation to understand the impacts of greenhouse gas (GHG)
      emission regulations and financial development levels on firms' GHG emissions, we
      build a two-stage dynamic game model to incorporate GHG emission regulations (in
      terms of an emission tax) and financial development (represented by the
      corresponding financing cost) into a two-echelon supply chain. With the subgame
      perfect equilibrium, we identify the conditions to determine whether an emission
      regulatory policy and/or financial development can affect GHG emissions in the
      supply chain. We also reveal the impacts of the strictness of GHG emission
      regulation, the financial development level, and the unit GHG emission rate on
      the operations of the supply chain and the corresponding profitability
      implications. Managerial insights are also discussed.

PMID- 29470453
TI  - UHPLC-UV Method for Simultaneous Determination of Perindopril Arginine and
      Indapamide Hemihydrate in Combined Dosage Form: A Stability-Indicating Assay
      Method.
AB  - Perindopril arginine and Indapamide hemihydrate in combination were proven to
      have a synergistic antihypertensive impact when compared with the use of each
      component alone. Therefore, a new Ultra-High Performance Liquid Chromatography
      coupled with Ultraviolet detector (UHPLC-UV) method has been developed and
      subsequently validated for simultaneous determination of the anti-hypertensive
      combination of Perindopril arginine and Indapamide hemihydrate. The separation of
      Perindopril arginine and Indapamide hemihydrate was achieved using a BEH C18 (1.7
      MUm, 2.1 * 50 mm) analytical column (Waters(r) Acquity UPLC) and a mobile phase
      composed of 0.01% v/v formic acid in water adjusted to pH 4 with acetic acid and
      acetonitrile (40:60 v/v). The method was able to separate Perindopril arginine
      and Indapamide hemihydrate within less than 4.5 min with high accuracy,
      precision, resolution, and sensitivity. The content of Perindopril arginine and
      Indapamide hemihydrate present in the dosage form Coversyl Plus(r) (5000 ug of
      Perindopril arginine/1250 ug of Indapamide hemihydrate) was determined in
      triplicate to give a concentration of 4991 ug and 1247 ug, respectively, from the
      manufacturer's stated amounts with Relative Standard Deviation (%RSD) of +/-0.63%
      for Perindopril arginine and +/-0.84% for Indapamide hemihydrate. Moreover, the
      degradation products of the combination were elucidated by UHPLC-Quadrupole Time
      of Flight-Mass spectrometry (UHPLC-QToF-MS) under acidic, basic, and thermal
      conditions. In conclusion, the developed UHPLC-UV method was sensitive, rapid,
      and precise. Furthermore, forced degradation studies were performed and the
      degradants were identified by UHPLC-Electro-Spray Ionization-QToF (UHPLC-ESI
      QToF).

PMID- 29470452
TI  - WHO Environmental Noise Guidelines for the European Region: A Systematic Review
      on Environmental Noise and Cardiovascular and Metabolic Effects: A Summary.
AB  - To update the current state of evidence and assess its quality, we conducted a
      systematic review on the effects of environmental noise exposure on the cardio
      metabolic systems as input for the new WHO environmental noise guidelines for the
      European Region. We identified 600 references relating to studies on effects of
      noise from road, rail and air traffic, and wind turbines on the cardio-metabolic
      system, published between January 2000 and August 2015. Only 61 studies,
      investigating different end points, included information enabling estimation of
      exposure response relationships. These studies were used for meta-analyses, and
      assessments of the quality of evidence using the Grading of Recommendations
      Assessment, Development and Evaluation (GRADE). A majority of the studies
      concerned traffic noise and hypertension, but most were cross-sectional and
      suffering from a high risk of bias. The most comprehensive evidence was available
      for road traffic noise and Ischeamic Heart Diseases (IHD). Combining the results
      of 7 longitudinal studies revealed a Relative Risk (RR) of 1.08 (95% CI: 1.01
      1.15) per 10 dB (LDEN) for the association between road traffic noise and the
      incidence of IHD. We rated the quality of this evidence as high. Only a few
      studies reported on the association between transportation noise and stroke,
      diabetes, and/or obesity. The quality of evidence for these associations was
      rated from moderate to very low, depending on transportation noise source and
      outcome. For a comprehensive assessment of the impact of noise exposure on the
      cardiovascular and metabolic system, we need more and better quality evidence,
      primarily based on longitudinal studies.

PMID- 29470454
TI  - Mineralization Induction of Gingival Fibroblasts and Construction of a Sandwich
      Tissue-Engineered Complex for Repairing Periodontal Defects.
AB  - BACKGROUND The ideal healing technique for periodontal tissue defects would
      involve the functional regeneration of the alveolar bone, cementum, and
      periodontal ligament, with new periodontal attachment formation. In this study,
      gingival fibroblasts were induced and a "sandwich" tissue-engineered complex (a
      tissue-engineered periodontal membrane between 2 tissue-engineered mineralized
      membranes) was constructed to repair periodontal defects. We evaluated the
      effects of gingival fibroblasts used as seed cells on the repair of periodontal
      defects and periodontal regeneration. MATERIAL AND METHODS Primitively cultured
      gingival fibroblasts were seeded bilaterally on Bio-Gide collagen membrane (a
      tissue-engineered periodontal membrane) or unilaterally on small intestinal
      submucosa segments, and their mineralization was induced. A tissue-engineered
      sandwich was constructed, comprising the tissue-engineered periodontal membrane
      flanked by 2 mineralized membranes. Periodontal defects in premolar regions of
      Beagles were repaired using the tissue-engineered sandwich or periodontal
      membranes. Periodontal reconstruction was compared to normal and trauma controls
      10 or 20 days postoperatively. RESULTS Periodontal defects were completely
      repaired by the sandwich tissue-engineered complex, with intact new alveolar bone
      and cementum, and a new periodontal ligament, 10 days postoperatively.
      CONCLUSIONS The sandwich tissue-engineered complex can achieve ideal periodontal
      reconstruction rapidly.

PMID- 29470455
TI  - Urban-Rural County and State Differences in Chronic Obstructive Pulmonary Disease
      - United States, 2015.
AB  - Chronic obstructive pulmonary disease (COPD) accounts for the majority of deaths
      from chronic lower respiratory diseases, the third leading cause of death in the
      United States in 2015 and the fourth leading cause in 2016.* Major risk factors
      include tobacco exposure, occupational and environmental exposures, respiratory
      infections, and genetics.? State variations in COPD outcomes (1) suggest that it
      might be more common in states with large rural areas. To assess urban-rural
      variations in COPD prevalence, hospitalizations, and mortality; obtain county
      level estimates; and update state-level variations in COPD measures, CDC analyzed
      2015 data from the Behavioral Risk Factor Surveillance System (BRFSS), Medicare
      hospital records, and death certificate data from the National Vital Statistics
      System (NVSS). Overall, 15.5 million adults aged >=18 years (5.9% age-adjusted
      prevalence) reported ever receiving a diagnosis of COPD; there were approximately
      335,000 Medicare hospitalizations (11.5 per 1,000 Medicare enrollees aged >=65
      years) and 150,350 deaths in which COPD was listed as the underlying cause for
      persons of all ages (40.3 per 100,000 population). COPD prevalence, Medicare
      hospitalizations, and deaths were significantly higher among persons living in
      rural areas than among those living in micropolitan or metropolitan areas. Among
      seven states in the highest quartile for all three measures, Arkansas, Kentucky,
      Mississippi, and West Virginia were also in the upper quartile (>=18%) for rural
      residents. Overcoming barriers to prevention, early diagnosis, treatment, and
      management of COPD with primary care provider education, Internet access,
      physical activity and self-management programs, and improved access to pulmonary
      rehabilitation and oxygen therapy are needed to improve quality of life and
      reduce COPD mortality.

PMID- 29470456
TI  - Notes from the Field: Increase in Acute Hepatitis B Infections - Pasco County,
      Florida, 2011-2016.

PMID- 29470457
TI  - HIV Diagnoses Among Persons Aged 13-29 Years - United States, 2010-2014.
AB  - In 2014, persons aged 13-29 years represented 23% of the U.S. population, yet
      accounted for 40% of diagnoses of human immunodeficiency virus (HIV) infection
      during the same year (1). During 2010-2014, the rates of diagnosis of HIV
      infection decreased among persons aged 15-19 years, were stable among persons
      aged 20-24 years, and increased among persons aged 25-29 years (1). However,
      these 5-year age groups encompass multiple developmental stages and potentially
      mask trends associated with the rapid psychosocial changes during adolescence
      through young adulthood. To better understand HIV infection among adolescents
      aged 13-17 years and young adults aged 18-29 years in the United States and
      identify ideal ages to target primary HIV prevention efforts, CDC analyzed data
      from the National HIV Surveillance System (NHSS)* using narrow age groups. During
      2010-2014, rates of diagnosis of HIV infection per 100,000 population varied
      substantially among persons aged 13-15 years (0.7), 16-17 years (4.5), 18-19
      years (16.5), and 20-21 years (28.6), and were higher, but less variable, among
      persons aged 22-23 years (34.0), 24-25 years (33.8), 26-27 years (31.3), and 28
      29 years (28.7). In light of the remarkable increase in rates between ages 16-17,
      18-19, and 20-21 years, and a recent study revealing that infection precedes
      diagnosis for young persons by an average of 2.7 years (2), these findings
      demonstrate the importance of targeting primary prevention efforts to persons
      aged <18 years and continuing through the period of elevated risk in their mid
      twenties.

PMID- 29470458
TI  - Prevalence of Amyotrophic Lateral Sclerosis - United States, 2014.
AB  - Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a
      progressive and fatal neuromuscular disease; the majority of ALS patients die
      within 2-5 years of receiving a diagnosis (1). Familial ALS, a hereditary form of
      the disease, accounts for 5%-10% of cases, whereas the remaining sporadic cases
      have no clearly defined etiology (1). ALS affects persons of all races and
      ethnicities; however, whites, males, non-Hispanics, persons aged >60 years, and
      those with a family history of ALS are more likely to develop the disease (1-3).
      No cure for ALS has yet been identified, and the lack of proven and effective
      therapeutic interventions is an ongoing challenge. Current treatments available
      do not cure ALS but have been shown to slow disease progression. Until recently,
      only one drug (riluzole) was approved to treat ALS; however, in 2017, the Food
      and Drug Administration approved a second drug, edaravone (4).

PMID- 29470460
TI  - Erratum: Vol. 67, No. 4.

PMID- 29470459
TI  - Prevalence of Self-Reported Hypertension and Antihypertensive Medication Use
      Among Adults Aged >=18 Years - United States, 2011-2015.
AB  - Hypertension, which affects nearly one third of adults in the United States, is a
      major risk factor for heart disease and stroke (1), and only approximately half
      of those with hypertension have their hypertension under control (2). The
      prevalence of hypertension is highest among non-Hispanic blacks, whereas the
      prevalence of antihypertensive medication use is lowest among Hispanics (1).
      Geographic variations have also been identified: a recent report indicated that
      the Southern region of the United States had the highest prevalence of
      hypertension as well as the highest prevalence of medication use (3). Using data
      from the Behavioral Risk Factor Surveillance System (BRFSS), this study found
      minimal change in state-level prevalence of hypertension awareness and treatment
      among U.S. adults during the first half of the current decade. From 2011 to 2015,
      the age-standardized prevalence of self-reported hypertension decreased slightly,
      from 30.1% to 29.8% (p = 0.031); among those with hypertension, the age
      standardized prevalence of medication use also decreased slightly, from 63.0% to
      61.8% (p<0.001). Persistent differences were observed by age, sex,
      race/ethnicity, level of education, and state of residence. Increasing
      hypertension awareness, as well as increasing hypertension control through
      lifestyle changes and consistent antihypertensive medication use, requires
      diverse clinical and public health intervention.

PMID- 29470461
TI  - Self-Reported Receipt of Advice and Action Taken To Reduce Dietary Sodium Among
      Adults With and Without Hypertension - Nine States and Puerto Rico, 2015.
AB  - Hypertension is a major cardiovascular disease risk factor (1,2). Advice given by
      health professionals can result in lower sodium intake and lower blood pressure
      (3).The 2017 Hypertension Guideline released by the American College of
      Cardiology and the American Heart Association emphasizes nonpharmacologic
      approaches, including sodium reduction, as important components of hypertension
      prevention and treatment (4). Data from 50,576 participants in the sodium module
      of the 2015 Behavioral Risk Factor Surveillance System (BRFSS) in nine states and
      Puerto Rico were analyzed to determine the prevalence of reported sodium
      reduction advice and action among participants with and without self-reported
      hypertension. Among participants with self-reported hypertension, adjusted
      prevalence of receiving sodium reduction advice from a health professional was
      41.9%, compared with 12.8% among participants without hypertension. Among those
      with hypertension, adjusted prevalence of reported action to reduce sodium intake
      was 80.9% among participants who received advice and 55.7% among those who did
      not receive advice. Among participants without hypertension, adjusted prevalence
      of taking action to reduce sodium intake was 72.7% among those who received
      advice and 46.9% among those who did not receive advice. The provision of advice
      on sodium reduction by health professionals is associated with respondent action
      to watch or reduce sodium intake. Fewer than half of patients with hypertension
      received this advice from their health professionals, a circumstance that
      represents a substantial missed opportunity to promote hypertension prevention
      and treatment.

PMID- 29470462
TI  - QuickStats: Age-Adjusted Percentage*,? of Adults Aged >=65 Years Who Had an
      Influenza Vaccine in the Past 12 Months,S by Poverty Status  - National Health
      Interview Survey, United States, 1999-2001 and 2014-2016.
AB  - During 2014-2016, 69.2% of all older adults, aged >=65 years, had received an
      influenza vaccine in the past 12 months. The percentage of older adults with
      family income >=200% poverty level who had received an influenza vaccine in the
      past 12 months significantly increased from 67.9% during 1999-2001 to 72.2%
      during 2014-2016. During the same period, the changes from 55.7% to 60.8% among
      those at the <100% poverty level and from 60.3% to 62.9% for those at the 100% to
      <200% poverty level were not statistically significant. During both periods,
      older adults with income >=200% poverty level were significantly more likely to
      receive an influenza vaccine compared with those with lower family income.

PMID- 29470463
TI  - Monitoring intracellular nanomolar calcium using fluorescence lifetime imaging.
AB  - Nanomolar-range fluctuations of intracellular [Ca2+] are critical for brain cell
      function but remain difficult to measure. We have advanced a microscopy technique
      to monitor intracellular [Ca2+] in individual cells in acute brain slices (also
      applicable in vivo) using fluorescence lifetime imaging (FLIM) of the Ca2+
      sensitive fluorescent indicator Oregon Green BAPTA1 (OGB-1). The OGB-1
      fluorescence lifetime is sensitive to [Ca2+] within the 10-500 nM range but not
      to other factors such as viscosity, temperature, or pH. This protocol describes
      the requirements, setup, and calibration of the FLIM system required for OGB-1
      imaging. We provide a step-by-step procedure for whole-cell OGB-1 loading and two
      photon FLIM. We also describe how to analyze the obtained FLIM data using total
      photon count and gated-intensity record, a ratiometric photon-counting approach
      that provides a highly improved signal-to-noise ratio and greater sensitivity of
      absolute [Ca2+] readout. We demonstrate our technique in nerve cells in situ, and
      it is adaptable to other cell types and fluorescent indicators. This protocol
      requires a basic understanding of FLIM and experience in single-cell
      electrophysiology and cell imaging. Setting up the FLIM system takes ~2 d, and
      OGB-1 loading, imaging, and data analysis take 2 d.

PMID- 29470464
TI  - Generation of human brain region-specific organoids using a miniaturized spinning
      bioreactor.
AB  - Human brain organoids, 3D self-assembled neural tissues derived from pluripotent
      stem cells, are important tools for studying human brain development and related
      disorders. Suspension cultures maintained by spinning bioreactors allow for the
      growth of large organoids despite the lack of vasculature, but commercially
      available spinning bioreactors are bulky in size and have low throughput. Here,
      we describe the procedures for building the miniaturized multiwell spinning
      bioreactor SpinOmega from 3D-printed parts and commercially available hardware.
      We also describe how to use SpinOmega to generate forebrain, midbrain and
      hypothalamus organoids from human induced pluripotent stem cells (hiPSCs). These
      organoids recapitulate key dynamic features of the developing human brain at the
      molecular, cellular and structural levels. The reduction in culture volume,
      increase in throughput and reproducibility achieved using our bioreactor and
      region-specific differentiation protocols enable quantitative modeling of brain
      disorders and compound testing. This protocol takes 14-84 d to complete
      (depending on the type of brain region-specific organoids and desired
      developmental stages), and organoids can be further maintained over 200 d.
      Competence with hiPSC culture is required for optimal results.

PMID- 29470466
TI  - E-cigarettes-peering into the mist of uncertainty.

PMID- 29470467
TI  - How comprehensive is suicide risk assessment in the emergency department?

PMID- 29470465
TI  - Genome-wide mapping of endogenous G-quadruplex DNA structures by chromatin
      immunoprecipitation and high-throughput sequencing.
AB  - G-rich DNA sequences can form four-stranded G-quadruplex (G4) secondary
      structures and are linked to fundamental biological processes such as
      transcription, replication and telomere maintenance. G4s are also implicated in
      promoting genome instability, cancer and other diseases. Here, we describe a
      detailed G4 ChIP-seq method that robustly enables the determination of G4
      structure formation genome-wide in chromatin. This protocol adapts traditional
      ChIP-seq for the detection of DNA secondary structures through the use of a G4
      structure-specific single-chain antibody with refinements in chromatin
      immunoprecipitation followed by high-throughput sequencing. This technology does
      not require expression of the G4 antibody in situ, enabling broad applicability
      to theoretically all chromatin sources. Beginning with chromatin isolation and
      antibody preparation, the entire protocol can be completed in <1 week, including
      basic computational analysis.

PMID- 29470468
TI  - An audit of risk assessments for suicide and attempted suicide in ED: a
      retrospective review of quality.
AB  - AIM: The primary aim of this audit was to determine the quality of psychiatric
      risk assessments conducted by Mental Health & Addiction Services clinicians for
      patients presenting to the emergency department, Waikato Hospital, Hamilton, New
      Zealand following an attempted suicide. METHOD: A retrospective, randomised audit
      of 376 files of patients who had presented to the ED over a 12-month period from
      1 July 2015 to 30 June 2016 was conducted, following the standards outlined in
      the present New Zealand Ministry of Health Clinical Practice Guideline for
      Deliberate Self Harm (DSH). RESULTS: It was found that clinicians routinely
      focused on the historical features of the suicide attempt presentation while
      failing to record judgements about future suicidal behaviours. Interactions with
      family members were recorded in less than half of the cases. The guideline most
      poorly adhered to was checking whether Maori patients wanted culturally
      appropriate services during the assessment and treatment planning, with this
      recorded in less than 10% of the clinical records. CONCLUSIONS: To improve the
      quality of the suicide risk assessments, and to better align with Clinical
      Practice Guidelines, the authors propose redevelopment of clinician training,
      including focus on cultural competence, and training in confidentiality and
      privacy relating to an attempted suicide episode.

PMID- 29470469
TI  - Acceptability of electronic cigarettes as an option to replace tobacco smoking
      for alcoholics admitted to hospital for detoxification.
AB  - AIM: A feasibility/acceptability trial was undertaken at Ward 5, Kenepuru
      Hospital, Porirua, to ascertain whether electronic cigarettes (e-cigarettes) were
      a useful option to replace or reduce smoking in the detoxification ward. METHODS:
      Two groups of patients were studied. Tobacco use and dependency data were
      collected for each. The first group was surveyed on the usefulness of standard
      nicotine replacement therapy (NRT). The second group were offered e-cigarettes
      with the option of standard NRT as well. All were asked to record their use of
      cigarettes, e-cigarettes and NRT during their stay on the ward, and to comment on
      their experiences. Outcomes monitored were self-reported use of NRT and of
      tobacco. Informal impressions of the nursing staff were also collected, where
      offered. For the e-cigarette group, a blood sample was taken on day 3 or 4 of
      their stay in hospital for nicotine/cotinine analysis, to confirm nicotine intake
      status. RESULTS: E-cigarettes were well tolerated as a form of nicotine
      replacement, eliciting positive comments, though they were not effective for all.
      The average reduction in median cigarettes per day was very similar between the
      group given standard NRT and the e-cigarette group, at 80% and 86% respectively.
      There were no adverse effects reported. CONCLUSION: The study showed that e
      cigarettes were an acceptable form of nicotine replacement for these alcohol
      dependent patients during their time in the ward. For heavily tobacco-dependent
      smokers, e-cigarettes may provide a useful aid to patient management within a
      hospital setting.

PMID- 29470470
TI  - Limiting complication rates in implant-based breast reconstruction.
AB  - BACKGROUND: External beam radiotherapy (XRT) to the breast has been shown to
      increase complication rates in women undergoing implant-based breast
      reconstruction (IBBR). Owing to concerns about high complication and failure
      rates, our department began to favour autologous reconstructive in patients
      requiring XRT in 2013. This study assesses the outcomes of IBBR prior to and
      following this policy change. METHODS: The records of all patients who underwent
      first-stage IBBR in 2012 and 2013 in our department were reviewed. Patients
      undergoing peri-operative XRT were identified. Complications and failure rates
      were analysed. RESULTS: Over two years, 77 IBBRs were performed in 53 patients.
      In 2012, 11 patients underwent peri-operative XTR compared with five in 2013.
      Radiotherapy was significantly associated with higher reconstructive failure
      rates while pre-operative XRT was associated with more complications overall
      (p=0.0099). Over the two years, the number of IBBRs with any complication fell
      from 16 (43.2%) to 11 (27.5%) while reconstructive failure fell from six (16.2%)
      to four (10%). CONCLUSIONS: Peri-operative XRT increases complication rates and
      reconstructive failure with IBBR. Our current policy of recommending autologous
      reconstruction if they have had pre-operative XRT seems to be resulting in
      decreased complication rates and increased reconstructive success.

PMID- 29470471
TI  - E-cigarette use in New Zealand-a systematic review and narrative synthesis.
AB  - AIM: This study aimed to systematically review the literature on e-cigarette use
      in New Zealand, focusing on prevalence, rationale for use, perceptions and
      exposure to the devices. METHODS: Six databases were systematically searched for
      articles regarding e-cigarette use in New Zealand, supplemented with a grey
      literature search. Seven hundred and eighteen abstracts were identified and full
      text of 100 articles reviewed. Studies addressing prevalence of and rationale for
      use, perceptions of and exposure to e-cigarettes were included. Relevant data
      were synthesised in a narrative summary. RESULTS: Fourteen studies addressed
      aspects of e-cigarette use in New Zealand, published between 2010 and 2017. Ever
      use of e-cigarettes among adults and adolescents has increased, although current
      use remains low. Smoking strongly predicts use, and ever-use may decrease with
      age. Investigation of other predictors has been hindered by low prevalence and
      small samples. While curiosity is commonly cited for sampling e-cigarettes, many
      smokers are drawn by harm reduction or cessation. More complex motivators are
      becoming evident. Although exposure to e-cigarettes is common, many remain
      uncertain about their harm relative to tobacco. CONCLUSION: While the available
      evidence provides an overview of current use, exposure and acceptance of e
      cigarettes in New Zealand, it highlights knowledge deficits and informs future
      monitoring.

PMID- 29470472
TI  - Ethnic- and sex-related differences in pain characteristics, psychological
      distress and pain-related disability in patients attending a New Zealand teaching
      hospital pain service.
AB  - AIM: The aim of the present observational study was to provide a description of
      the demographic, psychological and pain characteristics of patients attending the
      Waitemata Pain Services (WPS), Auckland, New Zealand. METHOD: Data were collected
      via a comprehensive paper-pencil questionnaire handed out to 798 consecutive new
      patients seen at the WPS over a four-year period. RESULTS: 32.3% attending the
      WPS were men and 67.7% women, with a mean age of 52.1 years. 65.7% of patients
      were New Zealand Europeans, followed by 19.1% other Europeans, 5.7% Asians, 3.9%
      Maori, 2.8% Middle Eastern/Latin/Africans and 2.7% Pacific Islanders. Patients
      reported an average of 2.6 visits to the GP before presenting to the unit.
      Average pain duration was seven years and seven months. Women reported a
      significantly higher number of pain sites in the whole body, as well as in the
      left and right side of the body compared to men (p<0.0001 for all). Highest
      interference due to pain was found for enjoyment of life. Men and women further
      differed in a range of psycho-behavioural variables, with women reporting less
      psychological distress and depression but more stress compared to men (p<0.05 for
      all). Men showed higher levels of kinesiophobia (p<0.005) and less pain
      acceptance and pain willingness (p<0.05 for both). Cross-cultural comparison
      found Maori patients reported highest pain levels, highest number of pain sites,
      highest pain interference, as well as highest levels of psychological distress,
      depression, stress and anxiety compared to all other ethnicities. Lowest pain
      severity was reported for New Zealand European patients and lowest interference
      due to pain for Pacific Islanders. While Middle Eastern/Latin/African patients
      showed highest levels of kinesiophobia, Pacific Islanders had the highest
      tendencies to catastrophise about their pain. CONCLUSION: There are important sex
      and ethnicity-related differences in the clinical presentation of chronic pain
      patients attending a large, hospital-based New Zealand pain service. While
      service provision can be based on generalised guidelines, specific interventions
      should be informed by important demographic and cultural variables. Studies are
      needed to identify strategies to improve service delivery in subgroups of the
      population who may be undertreated or lack access to appropriate interventions.

PMID- 29470473
TI  - Liver abscess: contemporary presentation and management in a Western population.
AB  - AIM: Historically, liver abscesses (LA) affected elderly, immunocompromised
      patients and were characterised by high morbidity and mortality, however there
      are no data pertaining to a New Zealand population with little information
      surrounding recent management trends. METHODS: A retrospective review of
      demographic characteristics, clinical management and microbiological data on
      patients presenting with liver abscess between 2005-2014 was conducted. RESULTS:
      Fifty-seven patients [37 males, median age 64 (range 15-87)] presented with LA
      and most patients were not comorbid. Ethnicity included European (47%), Chinese
      (16%) and Pacific Island (11%). Twenty-six patients had primary abscesses, 31
      patients had secondary abscesses [biliary disease, appendicitis, diverticular
      disease]. Presenting symptoms were non-specific. Admission white cell count was
      raised in 50 (88%) of patients and 43 (75%) had a CRP>=200mg/L. All patients were
      investigated with CT scan with 34 LA located in the right lobe, 14 in the left
      and eight bi-lobar. Klebsiella pneumoniae was the commonest pathogen (26% of
      aspirates). Percutaneous drainage (PD) was used to treat 36 of 37 patients, 17
      patients were treated with intravenous antibiotics alone and three patients
      required open drainage for loculated collections despite PD (n=1), intra
      peritoneal rupture or sepsis (n=2). Thirteen patients were readmitted within 30
      days for ongoing symptoms requiring intravenous antibiotics/further PD (9) or
      further investigations (4). The median PD duration was 10 days (range 3-53).
      Twenty-six patients required follow-up imaging over one month with 16 requiring
      follow-up over six weeks. CONCLUSION: In a New Zealand setting, LA affect fit
      patients, and primary abscesses account for almost half of all presentation. PD
      is effective treatment in most LA although prolonged drainage and treatment with
      antibiotics may be necessary.

PMID- 29470474
TI  - Monitoring pre-hospital transport of severely injured patients in the Midland
      Region of New Zealand.
AB  - AIM: Pre-hospital triage strategies aim to identify the type and extent of
      patient injuries and ensure that they are transferred to the most appropriate
      trauma centres. Despite the importance of appropriate pre-hospital transport,
      there is little evidence base to assist medical staff on optimal destination
      policy for emergent pre-hospital transport. This paper explores the spatial
      relationship of patient transfers prior to the implementation of the Midland Pre
      Hospital Trauma Destination Matrix in New Zealand, and is a retrospective view of
      practice against a destination policy that was applied after the study period.
      METHODS: We use data obtained from the Midland Trauma Registry merged with Global
      Positioning System (GPS) data from St John and Land Information New Zealand Data
      Service on major trauma occurring in 2014 and 2015. Using ArcGIS, data were
      analysed for spatial relationships between factors associated with major trauma
      events and pre-hospital transportation. RESULTS: In the retrospective analysis of
      162 major trauma patients, 107 (66%) were transported to a hospital that matched
      the destination specified in the Matrix, and 55 (34%) were transported to a non
      Matrix designated hospital. CONCLUSION: Approximately one-third of patients were
      not directly transported to the preferred definitive care hospital subsequently
      defined in the Midland Pre-Hospital Trauma Destination Matrix. Ongoing monitoring
      of the pre-hospital transportation system and the implementation of a formal pre
      hospital transport policy may improve the efficiency of the Midland Trauma
      System. Future studies should examine the possible reasons for variations in
      triage decisions across the Midland Region.

PMID- 29470475
TI  - Putting action into the revised Australian Medical Council standards on
      Aboriginal and Torres Strait Islander and Maori health.
AB  - Since 2006 the Australian Medical Council (AMC) accreditation standards have
      required medical schools to comprehensively address issues related to the health
      of Aboriginal and Torres Strait Islander peoples in Australia, and Maori in New
      Zealand. This has spanned areas of staff expertise, staff and student
      recruitment, curriculum and institutional leadership. These Indigenous specific
      standards have, until now, been absent for specialist medical college
      accreditation. The AMC revised its accreditation standards for specialist medical
      colleges in 2015, and for the first time included Indigenous specific standards.
      This commentary presents a guideline to support Australasian medical colleges'
      responsiveness to these Indigenous specific standards.

PMID- 29470476
TI  - Primary oral malignant melanoma of the tongue.

PMID- 29470477
TI  - Maori Indigenous Health Framework in action: addressing ethnic disparities in
      healthcare.
AB  - There has been a steady increase in cultural competency training in medical
      education programmes worldwide. To provide high-quality culturally competent care
      and reduce health disparities between Maori and non-Maori in New Zealand, several
      health models have been devised. The Indigenous Health Framework (IHF), currently
      taught at the University of Otago, Christchurch undergraduate medical programme,
      is a tool developed to assist health professionals to broaden their range of
      clinical assessment and communicate effectively with Maori patients and whanau,
      thereby improving health outcomes and reducing disparities. The authors of this
      article present a Maori health case study written from the observations of a
      trainee intern (first author) using components from the IHF to address health
      disparities between Maori and non-Maori.

PMID- 29470478
TI  - Factors influencing the smoking status of ex-prisoners reintegrating into the
      community after release: a pilot study.

PMID- 29470479
TI  - Ireland's new sugar tax: a step in the right direction.

PMID- 29470480
TI  - Reply to Mr Ryan's paper: acupuncture, ACC an d the Medicines Act.

PMID- 29470481
TI  - Alcohol harm-who pays?

PMID- 29470483
TI  - Errata.

PMID- 29470482
TI  - New Zealand's revised Ethnicity Data Protocols must not become a shelved
      document: a challenge from Hei Ahuru Mowai.

PMID- 29470484
TI  - The characteristic of asthma control among nasal diseases population: Results
      from a cross-sectional study.
AB  - Asthma affects a large number of patients in China, but comprehensive evaluation
      of risks associated with poor asthma control in asthmatic patients with nasal
      diseases was still limited. We conducted this study to provide a comprehensive
      estimate of asthma control in Chinese asthma patients with combined nasal
      diseases, to explore the effect of kinds of nasal diseases on the asthma control,
      and to identify risk factors associated with uncontrolled asthmatic patients with
      combined nasal diseases. 1756 asthma patients concomitant with nasal diseases
      aged >=17 years and representing all regions of mainland China were surveyed.
      Multivariate logistic regression model with all related demographic
      characteristics and disease characteristics factors entered was used to identify
      risk factors associated with uncontrolled asthma. 56.4% of asthmatic patients
      with combined allergic rhinitis or rhinosinusitis or rhinopolyp remained
      uncontrolled. Concomitant without allergic rhinitis, younger age, better
      treatment adherence and higher education level might positively impact asthma
      control among asthmatic patients with combined nasal diseases. Perennial allergic
      rhinitis (OR = 1.5, P = 0.021), moderate-severe allergic rhinitis (OR = 2.2, P =
      0.001) were all found to significantly increase the risk of uncontrolled asthma
      among asthma patients with combined allergic rhinitis. The high prevalence of
      uncontrolled asthma indicates that asthma management among adult Chinese
      asthmatic patients comorbid with nasal disease is still a challenge. Efforts
      should be made to raise the awareness of asthma management and to provide
      sufficient treatment will greatly contribute to improved quality of asthma
      management. It is possible to minimize the influence of allergic rhinitis on
      asthma control by improving nasal function, especially for more severe allergic
      rhinitis and perennial allergic rhinitis.

PMID- 29470485
TI  - An innovative HIV testing service using the internet: Anonymous urine delivery
      testing service at drugstores in Beijing, China.
AB  - Innovative human immunodeficiency virus (HIV) testing services will be needed to
      achieve the first 90 (90% of HIV-positive persons aware of their infection
      status) of the 90-90-90 target in China. Here, we describe an internet-based
      urine delivery testing service delivered through three pilot drugstores in
      Beijing that send specimens to a designated laboratory for HIV. From May 2016 to
      January 2017, we provided 500 HIV urine-testing service packs for display at the
      drugstores, and a total of 430 (86.0%) urine specimens were mailed back. All of
      the 430 urine specimens were of good quality and were tested. 70 urine specimens
      were HIV positive, showing a 16.3% (70/430) positivity rate. A total of 94.3%
      (66/70) of the HIV-positive participants obtained their test results through the
      internet, and 69.7% (46/66) of these participants received follow-up care. A
      total of 40 out of 46 (87.0%) participants agreed to have their results confirmed
      by a blood test, and 39 out of 40 (97.5%) participants were confirmed as HIV-1
      positive, including two individuals that were previously diagnosed. Lastly, 28
      out of 37 (75.7%) of the study participants were referred to the hospital and
      provided free antiviral treatment. Our data indicate that this innovative HIV
      testing service is effective and play an important role in HIV testing and
      surveillance.

PMID- 29470486
TI  - Lassa fever-induced sensorineural hearing loss: A neglected public health and
      social burden.
AB  - Although an association between Lassa fever (LF) and sudden-onset sensorineural
      hearing loss (SNHL) was confirmed clinically in 1990, the prevalence of LF
      induced SNHL in endemic countries is still underestimated. LF, a viral
      hemorrhagic fever disease caused by Lassa virus (LASV), is endemic in West
      Africa, causing an estimated 500,000 cases and 5,000 deaths per year. Sudden
      onset SNHL, one complication of LF, occurs in approximately one-third of
      survivors and constitutes a neglected public health and social burden. In the
      endemic countries, where access to hearing aids is limited, SNHL results in a
      decline of the quality of life for those affected. In addition, hearing loss
      costs Nigeria approximately 43 million dollars per year. The epidemiology of LF
      induced SNHL has not been characterized well. The complication of LF induced by
      SNHL is also an important consideration for vaccine development and treatments.
      However, research into the mechanism has been hindered by the lack of autopsy
      samples and relevant small animal models. Recently, the first animal model that
      mimics the symptoms of SNHL associated with LF was developed. Preliminary data
      from the new animal model as well as the clinical case studies support the
      mechanism of immune-mediated injury that causes SNHL in LF patients. This article
      summarizes clinical findings of hearing loss in LF patients highlighting the
      association between LASV infection and SNHL as well as the potential mechanism(s)
      for LF-induced SNHL. Further research is necessary to identify the mechanism and
      the epidemiology of LF-induced SNHL.

PMID- 29470487
TI  - Sex: Not all that it's cracked up to be?

PMID- 29470488
TI  - Intracellular amyloid beta expression leads to dysregulation of the mitogen
      activated protein kinase and bone morphogenetic protein-2 signaling axis.
AB  - Alzheimer's disease (AD) is a neurodegenerative syndrome classically depicted by
      the parenchymal accumulation of extracellular amyloid beta plaques. However,
      recent findings suggest intraneuronal amyloid beta (iAbeta1-42) accumulation
      precedes extracellular deposition. Furthermore, the pathologic increase in
      iAbeta1-42 has been implicated in dysregulation of cellular mechanisms critically
      important in axonal transport. Owing to neuronal cell polarity, retrograde and
      anterograde axonal transport are essential trafficking mechanism necessary to
      convey membrane bound neurotransmitters, neurotrophins, and endosomes between
      soma and synaptic interfaces. Although iAbeta1-42 disruption of axonal transport
      has been implicated in dysregulation of neuronal synaptic transmission, the role
      of iAbeta1-42 and its influence on signal transduction involving the mitogen
      activated protein kinase (MAPK) and morphogenetic signaling axis are unknown. Our
      biochemical characterization of intracellular amyloid beta accumulation on MAPK
      and morphogenetic signaling have revealed increased iAbeta1-42 expression leads
      to significant reduction in ERK 1/2 phosphorylation and increased bone
      morphogenetic protein 2 dependent Smad 1/5/8 phosphorylation. Furthermore, rescue
      of iAbeta1-42 mediated attenuation of MAPK signaling can be accomplished with the
      small molecule PLX4032 as a downstream enhancer of the MAPK pathway.
      Consequently, our observations regarding the dysregulation of these gatekeepers
      of neuronal viability may have important implications in understanding the
      iAbeta1-42 mediated effects observed in AD.

PMID- 29470489
TI  - Integration of machine learning and meta-analysis identifies the transcriptomic
      bio-signature of mastitis disease in cattle.
AB  - Gram-negative bacteria such as Escherichia coli (E. coli) are assumed to be among
      the main agents that cause severe mastitis disease with clinical signs in dairy
      cattle. Rapid detection of this disease is so important in order to prevent
      transmission to other cows and helps to reduce inappropriate use of antibiotics.
      With the rapid progress in high-throughput technologies, and accumulation of
      various kinds of '-omics' data in public repositories, there is an opportunity to
      retrieve, integrate, and reanalyze these resources to improve the diagnosis and
      treatment of different diseases and to provide mechanistic insights into host
      resistance in an efficient way. Meta-analysis is a relatively inexpensive option
      with good potential to increase the statistical power and generalizability of
      single-study analysis. In the current meta-analysis research, six microarray
      based studies that investigate the transcriptome profile of mammary gland tissue
      after induced mastitis by E. coli infection were used. This meta-analysis not
      only reinforced the findings in individual studies, but also several novel terms
      including responses to hypoxia, response to drug, anti-apoptosis and positive
      regulation of transcription from RNA polymerase II promoter enriched by up
      regulated genes. Finally, in order to identify the small sets of genes that are
      sufficiently informative in E. coli mastitis, the differentially expressed gene
      introduced by meta-analysis were prioritized by using ten different attribute
      weighting algorithms. Twelve meta-genes were detected by the majority of
      attribute weighting algorithms (with weight above 0.7) as most informative genes
      including CXCL8 (IL8), NFKBIZ, HP, ZC3H12A, PDE4B, CASP4, CXCL2, CCL20,
      GRO1(CXCL1), CFB, S100A9, and S100A8. Interestingly, the results have been
      demonstrated that all of these genes are the key genes in the immune response,
      inflammation or mastitis. The Decision tree models efficiently discovered the
      best combination of the meta-genes as bio-signature and confirmed that some of
      the top-ranked genes -ZC3H12A, CXCL2, GRO, CFB- as biomarkers for E. coli
      mastitis (with the accuracy 83% in average). This research properly indicated
      that by combination of two novel data mining tools, meta-analysis and machine
      learning, increased power to detect most informative genes that can help to
      improve the diagnosis and treatment strategies for E. coli associated with
      mastitis in cattle.

PMID- 29470490
TI  - Neutralization of cholera toxin with nanoparticle decoys for treatment of
      cholera.
AB  - Diarrheal diseases are a major cause of morbidity and mortality worldwide. In
      many cases, antibiotic therapy is either ineffective or not recommended due to
      concerns about emergence of resistance. The pathogenesis of several of the most
      prevalent infections, including cholera and enteroxigenic Escherichia coli, is
      dominated by enterotoxins produced by lumen-dwelling pathogens before clearance
      by intestinal defenses. Toxins gain access to the host through critical host
      receptors, making these receptors attractive targets for alternative
      antimicrobial strategies that do not rely on conventional antibiotics. Here, we
      developed a new nanotechnology strategy as a countermeasure against cholera, one
      of the most important and prevalent toxin-mediated enteric infections. The key
      host receptor for cholera toxin, monosialotetrahexosylganglioside (GM1), was
      coated onto the surface of polymeric nanoparticles. The resulting GM1-polymer
      hybrid nanoparticles were shown to function as toxin decoys by selectively and
      stably binding cholera toxin, and neutralizing its actions on epithelial cells in
      vitro and in vivo. Furthermore, the GM1-coated nanoparticle decoys attenuated
      epithelial 3',5'-cyclic adenosine monophosphate production and fluid responses to
      infection with live Vibrio cholera in cell culture and a murine infection model.
      Together, these studies illustrate that the new nanotechnology-based platform can
      be employed as a non-traditional antimicrobial strategy for the management of
      enteric infections with enterotoxin-producing pathogens.

PMID- 29470491
TI  - Emergence of Klebsiella pneumoniae subspecies pneumoniae as a cause of
      septicaemia in pigs in England.
AB  - Between 2011 and 2014 outbreaks of septicaemia due to Klebsiella pneumoniae
      subspecies pneumoniae (Kpp) were diagnosed on thirteen English pig farms. The
      most consistent features were rapid deaths of pigs from ten-days-old to weaning,
      seasonal occurrence (May to September), affected farms being outdoor breeding
      herds and the location of all but one of the outbreaks in the East Anglia region
      in Eastern England. Molecular characterisation of the outbreak Kpp isolates
      showed that by multilocus sequencing all were sequence type 25 (ST25) of K2
      capsular type with a combination of a 4.3kb plasmid (pKPMC25), three phage
      sequences and the rmpA virulence gene. No archived Kpp isolates of porcine origin
      pre-dating 2011 were identified as ST25. In 2013 there was the first detection of
      an outbreak Kpp isolate showing antimicrobial resistance to six antibiotics.
      Human infection with Kpp ST25 has not been reported in the UK.

PMID- 29470492
TI  - Memory functions reveal structural properties of gene regulatory networks.
AB  - Gene regulatory networks (GRNs) control cellular function and decision making
      during tissue development and homeostasis. Mathematical tools based on dynamical
      systems theory are often used to model these networks, but the size and
      complexity of these models mean that their behaviour is not always intuitive and
      the underlying mechanisms can be difficult to decipher. For this reason, methods
      that simplify and aid exploration of complex networks are necessary. To this end
      we develop a broadly applicable form of the Zwanzig-Mori projection. By first
      converting a thermodynamic state ensemble model of gene regulation into mass
      action reactions we derive a general method that produces a set of time evolution
      equations for a subset of components of a network. The influence of the rest of
      the network, the bulk, is captured by memory functions that describe how the
      subnetwork reacts to its own past state via components in the bulk. These memory
      functions provide probes of near-steady state dynamics, revealing information not
      easily accessible otherwise. We illustrate the method on a simple cross
      repressive transcriptional motif to show that memory functions not only simplify
      the analysis of the subnetwork but also have a natural interpretation. We then
      apply the approach to a GRN from the vertebrate neural tube, a well characterised
      developmental transcriptional network composed of four interacting transcription
      factors. The memory functions reveal the function of specific links within the
      neural tube network and identify features of the regulatory structure that
      specifically increase the robustness of the network to initial conditions. Taken
      together, the study provides evidence that Zwanzig-Mori projections offer
      powerful and effective tools for simplifying and exploring the behaviour of GRNs.

PMID- 29470493
TI  - Effective polyploidy causes phenotypic delay and influences bacterial
      evolvability.
AB  - Whether mutations in bacteria exhibit a noticeable delay before expressing their
      corresponding mutant phenotype was discussed intensively in the 1940s to 1950s,
      but the discussion eventually waned for lack of supportive evidence and perceived
      incompatibility with observed mutant distributions in fluctuation tests.
      Phenotypic delay in bacteria is widely assumed to be negligible, despite the lack
      of direct evidence. Here, we revisited the question using recombineering to
      introduce antibiotic resistance mutations into E. coli at defined time points and
      then tracking expression of the corresponding mutant phenotype over time.
      Contrary to previous assumptions, we found a substantial median phenotypic delay
      of three to four generations. We provided evidence that the primary source of
      this delay is multifork replication causing cells to be effectively polyploid,
      whereby wild-type gene copies transiently mask the phenotype of recessive mutant
      gene copies in the same cell. Using modeling and simulation methods, we explored
      the consequences of effective polyploidy for mutation rate estimation by
      fluctuation tests and sequencing-based methods. For recessive mutations, despite
      the substantial phenotypic delay, the per-copy or per-genome mutation rate is
      accurately estimated. However, the per-cell rate cannot be estimated by existing
      methods. Finally, with a mathematical model, we showed that effective polyploidy
      increases the frequency of costly recessive mutations in the standing genetic
      variation (SGV), and thus their potential contribution to evolutionary
      adaptation, while drastically reducing the chance that de novo recessive
      mutations can rescue populations facing a harsh environmental change such as
      antibiotic treatment. Overall, we have identified phenotypic delay and effective
      polyploidy as previously overlooked but essential components in bacterial
      evolvability, including antibiotic resistance evolution.

PMID- 29470494
TI  - Fish mutant, where is thy phenotype?

PMID- 29470495
TI  - Reproducibility of preclinical animal research improves with heterogeneity of
      study samples.
AB  - Single-laboratory studies conducted under highly standardized conditions are the
      gold standard in preclinical animal research. Using simulations based on 440
      preclinical studies across 13 different interventions in animal models of stroke,
      myocardial infarction, and breast cancer, we compared the accuracy of effect size
      estimates between single-laboratory and multi-laboratory study designs. Single
      laboratory studies generally failed to predict effect size accurately, and larger
      sample sizes rendered effect size estimates even less accurate. By contrast,
      multi-laboratory designs including as few as 2 to 4 laboratories increased
      coverage probability by up to 42 percentage points without a need for larger
      sample sizes. These findings demonstrate that within-study standardization is a
      major cause of poor reproducibility. More representative study samples are
      required to improve the external validity and reproducibility of preclinical
      animal research and to prevent wasting animals and resources for inconclusive
      research.

PMID- 29470496
TI  - Reduced-order modeling of soft robots.
AB  - We present a general strategy for the modeling and simulation-based control of
      soft robots. Although the presented methodology is completely general, we
      restrict ourselves to the analysis of a model robot made of hyperelastic
      materials and actuated by cables or tendons. To comply with the stringent real
      time constraints imposed by control algorithms, a reduced-order modeling strategy
      is proposed that allows to minimize the amount of online CPU cost. Instead, an
      offline training procedure is proposed that allows to determine a sort of
      response surface that characterizes the response of the robot. Contrarily to
      existing strategies, the proposed methodology allows for a fully non-linear
      modeling of the soft material in a hyperelastic setting as well as a fully non
      linear kinematic description of the movement without any restriction nor
      simplifying assumption. Examples of different configurations of the robot were
      analyzed that show the appeal of the method.

PMID- 29470497
TI  - Most yeast SH3 domains bind peptide targets with high intrinsic specificity.
AB  - A need exists to develop bioinformatics for predicting differences in protein
      function, especially for members of a domain family who share a common fold, yet
      are found in a diverse array of proteins. Many domain families have been
      conserved over large evolutionary spans and representative genomic data during
      these periods are now available. This allows a simple method for grouping domain
      sequences to reveal common and unique/specific binding residues. As such, we
      hypothesize that sequence alignment analysis of the yeast SH3 domain family
      across ancestral species in the fungal kingdom can determine whether each member
      encodes specific information to bind unique peptide targets. With this approach,
      we identify important specific residues for a given domain as those that show
      little conservation within an alignment of yeast domain family members (paralogs)
      but are conserved in an alignment of its direct relatives (orthologs). We find
      most of the yeast SH3 domain family members have maintained unique amino acid
      conservation patterns that suggest they bind peptide targets with high intrinsic
      specificity through varying degrees of non-canonical recognition. For a minority
      of domains, we predict a less diverse binding surface, likely requiring
      additional factors to bind targets specifically. We observe that our predictions
      are consistent with high throughput binding data, which suggests our approach can
      probe intrinsic binding specificity in any other interaction domain family that
      is maintained during evolution.

PMID- 29470498
TI  - U-shaped association between sleep duration and urinary albumin excretion in
      Korean adults: 2011-2014 Korea National Health and Nutrition Examination Survey.
AB  - Although sleep duration has been extensively studied in metabolic diseases, few
      studies have investigated the impact of sleep duration on chronic kidney disease.
      The aim of this study was to examine the relationship between sleep duration and
      albuminuria in the general population. Among 24,948 adults who participated in
      the 2011-2014 KNHANES, a total of 19,994 subjects were included in this analysis.
      Subjects were categorized into the following five groups according to self
      reported sleep duration: less than 5 h, 6 h, 7 h, 8 h, and more than 9 h. The
      association between sleep duration and urinary albumin-creatinine ratio (UACR)
      was examined cross-sectionally. Subjects with both short and long sleep durations
      were significantly associated with higher UACR levels and higher proportions of
      patients with microalbuminuria (30-299 mg/g) and macroalbuminuria (>=300 mg/g)
      compared to those with a sleep duration of 7 hours. The U-shaped association
      between sleep duration and UACR remained significant even after adjustment for
      potential confounders, including age, sex, body mass index, smoking, alcohol,
      education, income, exercise, estimated glomerular filtration rate, diabetes
      mellitus, hypertension and hypercholesterolemia. The U-shaped association is more
      evident in the subgroup aged 65 or older, or in female subjects. Our findings
      suggest that both short and long sleep durations have a U-shaped association with
      UACR levels in the general population, independent of potential confounders.

PMID- 29470499
TI  - Unveiling relationships between crime and property in England and Wales via
      density scale-adjusted metrics and network tools.
AB  - Scale-adjusted metrics (SAMs) are a significant achievement of the urban scaling
      hypothesis. SAMs remove the inherent biases of per capita measures computed in
      the absence of isometric allometries. However, this approach is limited to urban
      areas, while a large portion of the world's population still lives outside cities
      and rural areas dominate land use worldwide. Here, we extend the concept of SAMs
      to population density scale-adjusted metrics (DSAMs) to reveal relationships
      among different types of crime and property metrics. Our approach allows all
      human environments to be considered, avoids problems in the definition of urban
      areas, and accounts for the heterogeneity of population distributions within
      urban regions. By combining DSAMs, cross-correlation, and complex network
      analysis, we find that crime and property types have intricate and hierarchically
      organized relationships leading to some striking conclusions. Drugs and burglary
      had uncorrelated DSAMs and, to the extent property transaction values are
      indicators of affluence, twelve out of fourteen crime metrics showed no evidence
      of specifically targeting affluence. Burglary and robbery were the most connected
      in our network analysis and the modular structures suggest an alternative to
      "zero-tolerance" policies by unveiling the crime and/or property types most
      likely to affect each other.

PMID- 29470500
TI  - Glutathionylation of dengue and Zika NS5 proteins affects guanylyltransferase and
      RNA dependent RNA polymerase activities.
AB  - It has been estimated for dengue infection that the global population at risk is
      3.5 billion people, which makes dengue an important public health problem. The
      causative agents of dengue are dengue viruses. For dengue virus replication, the
      dengue virus NS5 protein is of special importance as it has several enzyme
      activities important for viral replication. Previous reports of phosphorylation
      and SUMOylation of dengue NS5 have shown these protein modifications have
      important consequences for NS5 functions. In this report we identify
      glutathionylation, another reversible post translation modification that impacts
      on NS5 enzyme activity. Using dengue virus infected cells we employed specific
      antibodies and mass spectrometry to identify 3 cysteine residues of NS5 protein
      as being glutathionylated. Glutathionylation is a post translational protein
      modification where glutathione is covalently attached to a cysteine residue. We
      showed glutathionylation occurs on 3 conserved cysteine residues of dengue NS5.
      Then we generated two flavivirus recombinant full length proteins, dengue NS5 and
      Zika NS5, to characterize two of the NS5 enzyme activities, namely,
      guanylyltransferase and RNA-dependent RNA polymerase activities. We show
      glutathionylation of dengue and Zika NS5 affects enzyme activities of the two
      flavivirus proteins. The data suggests that glutathionylation is a general
      feature of the flavivirus NS5 protein and the modification has the potential to
      modulate several of the NS5 enzyme functions.

PMID- 29470501
TI  - Tissue-specific and mosaic imprinting defects underlie opposite congenital growth
      disorders in mice.
AB  - Differential DNA methylation defects of H19/IGF2 are associated with congenital
      growth disorders characterized by opposite clinical pictures. Due to structural
      differences between human and mouse, the mechanisms by which mutations of the
      H19/IGF2 Imprinting Control region (IC1) result in these diseases are undefined.
      To address this issue, we previously generated a mouse line carrying a humanized
      IC1 (hIC1) and now replaced the wildtype with a mutant IC1 identified in the
      overgrowth-associated Beckwith-Wiedemann syndrome. The new humanized mouse line
      shows pre/post-natal overgrowth on maternal transmission and pre/post-natal
      undergrowth on paternal transmission of the mutation. The mutant hIC1 acquires
      abnormal methylation during development causing opposite H19/Igf2 imprinting
      defects on maternal and paternal chromosomes. Differential and possibly mosaic
      Igf2 expression and imprinting is associated with asymmetric growth of bilateral
      organs. Furthermore, tissue-specific imprinting defects result in deficient liver
      and placenta-derived Igf2 on paternal transmission and excessive Igf2 in
      peripheral tissues on maternal transmission, providing a possible molecular
      explanation for imprinting-associated and phenotypically contrasting growth
      disorders.

PMID- 29470502
TI  - Chronic Obstructive Pulmonary Disease (COPD) as a disease of early aging:
      Evidence from the EpiChron Cohort.
AB  - BACKGROUND: Aging is an important risk factor for most chronic diseases. Patients
      with COPD develop more comorbidities than non-COPD subjects. We hypothesized that
      the development of comorbidities characteristically affecting the elderly occur
      at an earlier age in subjects with the diagnosis of COPD. METHODS AND FINDINGS:
      We included all subjects carrying the diagnosis of COPD (n = 27,617), and a
      similar number of age and sex matched individuals without the diagnosis,
      extracted from the 727,241 records of individuals 40 years and older included in
      the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of
      comorbidities, their prevalence and the mortality risk between both groups. Using
      network analysis, we explored the connectivity between comorbidities and the most
      influential comorbidities in both groups. We divided the groups into 5
      incremental age categories and compared their comorbidity networks. We then
      selected those comorbidities known to affect primarily the elderly and compared
      their prevalence across the 5 age groups. In addition, we replicated the analysis
      in the smokers' subgroup to correct for the confounding effect of cigarette
      smoking. Subjects with COPD had more comorbidities and died at a younger age
      compared to controls. Comparison of both cohorts across 5 incremental age groups
      showed that the number of comorbidities, the prevalence of diseases
      characteristic of aging and network's density for the COPD group aged 56-65 were
      similar to those of non-COPD 15 to 20 years older. The findings persisted after
      adjusting for smoking. CONCLUSION: Multimorbidity increases with age but in
      patients carrying the diagnosis of COPD, these comorbidities are seen at an
      earlier age.

PMID- 29470503
TI  - Sevoflurane posttreatment prevents oxidative and inflammatory injury in
      ventilator-induced lung injury.
AB  - Mechanical ventilation is a life-saving clinical treatment but it can induce or
      aggravate lung injury. New therapeutic strategies, aimed at reducing the negative
      effects of mechanical ventilation such as excessive production of reactive oxygen
      species, release of pro-inflammatory cytokines, and transmigration as well as
      activation of neutrophil cells, are needed to improve the clinical outcome of
      ventilated patients. Though the inhaled anesthetic sevoflurane is known to exert
      organ-protective effects, little is known about the potential of sevoflurane
      therapy in ventilator-induced lung injury. This study focused on the effects of
      delayed sevoflurane application in mechanically ventilated C57BL/6N mice. Lung
      function, lung injury, oxidative stress, and inflammatory parameters were
      analyzed and compared between non-ventilated and ventilated groups with or
      without sevoflurane anesthesia. Mechanical ventilation led to a substantial
      induction of lung injury, reactive oxygen species production, pro-inflammatory
      cytokine release, and neutrophil influx. In contrast, sevoflurane posttreatment
      time dependently reduced histological signs of lung injury. Most interestingly,
      increased production of reactive oxygen species was clearly inhibited in all
      sevoflurane posttreatment groups. Likewise, the release of the pro-inflammatory
      cytokines interleukin-1beta and MIP-1beta and neutrophil transmigration were
      completely prevented by sevoflurane independent of the onset of sevoflurane
      administration. In conclusion, sevoflurane posttreatment time dependently limits
      lung injury, and oxidative and pro-inflammatory responses are clearly prevented
      by sevoflurane irrespective of the onset of posttreatment. These findings
      underline the therapeutic potential of sevoflurane treatment in ventilator
      induced lung injury.

PMID- 29470504
TI  - Predicting the duration of reach-to-grasp movements to objects with asymmetric
      contact surfaces.
AB  - The duration of reach-to-grasp movements is influenced by the size of the contact
      surfaces, such that grasping objects with smaller contact surface areas takes
      longer. But what is the influence of asymmetric contact surfaces? In Experiment
      1a, participants reached-to-lift wooden blocks off a table top, with the contact
      locations for the thumb and index finger varying in surface size. The time taken
      to lift the block was driven primarily by the thumb contact surface, which showed
      a larger effect size for the dependent variable of movement duration than the
      index finger's contact surface. In Experiment 1b participants reached-to-grasp
      (but not lift) the blocks. The same effect was found with duration being largely
      driven by contact surface size for the thumb. Experiment 2 tested whether this
      finding generalised to movements towards conical frusta grasped in a different
      plane mounted off the table top. Experiment 2 showed that movement duration again
      was dictated primarily by the size of the thumb's contact surface. The thumb
      contact surface was the visible surface in experiments 1 and 2 so Experiment 3
      explored grasping when the index finger's contact surface was visible
      (participants grasped the frusta with the index finger at the top). An
      interaction between thumb and finger surface size was now found to determine
      movement duration. These findings provide the first empirical report of the
      impact of asymmetric contact surfaces on prehension, and may have implications
      for scientists who wish to model reach-to-grasp behaviours.

PMID- 29470505
TI  - Grunting's competitive advantage: Considerations of force and distraction.
AB  - BACKGROUND: Grunting is pervasive in many athletic contests, and empirical
      evidence suggests that it may result in one exerting more physical force. It may
      also distract one's opponent. That grunts can distract was supported by a study
      showing that it led to an opponent being slower and more error prone when viewing
      tennis shots. An alternative explanation was that grunting masks the sound of a
      ball being hit. The present study provides evidence against this alternative
      explanation by testing the effect of grunting in a sport-mixed martial arts-where
      distraction, rather than masking, is the most likely mechanism.
      METHODOLOGY/PRINCIPAL FINDINGS: We first confirmed that kicking force is
      increased when a grunt is performed (Experiment 1), and then adapted methodology
      used in the tennis study to mixed martial arts (Experiment 2). Lifting the foot
      to kick is a silent act, and therefore there is nothing for a grunt to mask,
      i.e., its effect on an opponent's response time and/or accuracy can likely be
      attributed to attentional distraction. Participants viewed videos of a trained
      mixed martial artist kicking that included, or did not include, a simulated
      grunt. The task was to determine as quickly as possible whether the kick was
      traveling upward or downward. Overall, and replicating the tennis finding, the
      present results indicate that a participant's response to a kick was delayed and
      more error prone when a simulated grunt was present. CONCLUSIONS/SIGNIFICANCE:
      The present findings indicate that simulated grunting may distract an opponent,
      leading to slower and more error prone responses. The implications for martial
      arts in particular, and the broader question of whether grunting should be
      perceived as 'cheating' in sports, are examined.

PMID- 29470506
TI  - Cuticular hydrocarbons correlate with queen reproductive status in native and
      invasive Argentine ants (Linepithema humile, Mayr).
AB  - In insect societies, chemical communication plays an important role in colony
      reproduction and individual social status. Many studies have indicated that
      cuticular hydrocarbons (CHCs) are the main chemical compounds encoding
      reproductive status. However, these studies have largely focused on queenless or
      monogynous species whose workers are capable of egg laying and have mainly
      explored the mechanisms underlying queen-worker or worker-worker reproductive
      conflicts. Less is known about what occurs in highly polygynous ant species with
      permanently sterile workers. Here, we used the Argentine ant as a model to
      examine the role of CHCs in communicating reproductive information in such insect
      societies. The Argentine ant is unicolonial, highly polygynous, and polydomous.
      We identified several CHCs whose presence and levels were correlated with queen
      age, reproductive status, and fertility. Our results also provide new insights
      into queen executions in the Argentine ant, a distinctive feature displayed by
      this species in its introduced range. Each spring, just before new sexuals
      appear, workers eliminate up to 90% of the mated queens in their colonies. We
      discovered that queens that survived execution had different CHC profiles from
      queens present before and during execution. More specifically, levels of some
      CHCs were higher in the survivors, suggesting that workers could eliminate queens
      based on their chemical profiles. In addition, queen CHC profiles differed based
      on season and species range (native vs. introduced). Overall, the results of this
      study provide new evidence that CHCs serve as queen signals and do more than just
      regulate worker reproduction.

PMID- 29470507
TI  - Vehicle development, pharmacokinetics and toxicity of the anti-invasive agent 4
      fluoro-3',4',5'-trimethoxychalcone in rodents.
AB  - Effective inhibitors of invasion and metastasis represent a serious unmet
      clinical need. We have recently identified 4-fluoro-3',4',5'-trimethoxychalcone
      or C16 as a potent anti-invasive molecule. In this paper, we report on the
      development of an optimized vehicle for oral administration of C16. We also
      explore its pharmacokinetic and toxicity profile in rodents as a prelude to a
      broad-scope evaluation as a pharmacological tool in animal models of disease. C16
      showed suboptimal pharmacokinetics with limited oral bioavailability and whole
      blood stability. Rapid metabolism with elimination via glutathione conjugation
      was observed. An oral dosing routine using medicated gels was developed to
      overcome bioavailability issues and yielded sustained whole blood levels above
      the half maximal effective concentration (EC50) in a 7-day study. The compound
      proved well-tolerated in acute and chronic experiments at 300 mg/kg PO dosing.
      The medicated gel formulation is highly suitable for evaluation of C16 in animal
      models of disease.

PMID- 29470508
TI  - Preterm delivery and small-for-gestation outcomes in HIV-infected pregnant women
      on antiretroviral therapy in rural South Africa: Results from a cohort study,
      2010-2015.
AB  - OBJECTIVES: Increasingly more women conceive on antiretroviral therapy (ART) with
      non-nucleoside reverse transcriptase-based regimens. This study assessed the
      effect of preconception tenofovir disoproxil fumarate (TDF)-lamivudine
      (3TC)/emtricitabine (FTC)-efavirenz (EFV) and post-conception TDF-(3TC/FTC)-EFV
      (versus other regimens) on preterm delivery (PTD) and small-for-gestational age
      (SGA) births. METHODS: We analysed data of 2549 HIV-infected women attending
      antenatal clinics in KwaZulu-Natal from 2010 through 2015 in this retrospective
      cohort study. Preconception, TDF-(3TC/FTC)-EFV was compared to nevirapine (NVP)
      based regimens and other 3-drug EFV-based regimens. Post-conception, TDF
      (3TC/FTC)-EFV was compared to NVP-based ART and zidovudine (ZDV) prophylaxis.
      Outcomes included PTD <37 weeks and SGA births. Generalized linear mixed effects
      were used to fit logistic regression models to account for repeat pregnancies.
      RESULTS: Among 2549 singleton live births, 10.4% (n = 264) were PTD and 10.4% (n
      = 265) SGA. PTD declined from 16.3% in 2010 to 9.3% in 2015 and SGA remained
      stable from 9.9% in 2010 to 10% in 2015. Preconception NVP-based regimens
      [adjusted odds ratio (aOR) 0.66; 95% CI 0.27-1.63] and other 3-drug EFV-based
      regimens (aOR 0.72; 95% CI 0.24-2.12) were not associated with PTD versus TDF
      (3TC/FTC)-EFV. NVP-based (aOR 0.75; 95% CI 0.40-1.42) and other 3-drug EFV-based
      regimens (aOR 1.55; 95% CI 0.76-3.16) were not associated with SGA births versus
      TDF-(3TC/FTC)-EFV. Post-conception NVP-based ART (1.77; 95% CI 0.89-3.51) and ZDV
      (1.03; 95% CI 0.68-1.58) were not associated with PTD versus TDF-(3TC/FTC)-EFV.
      NVP-based ART (1.55; 95% CI 0.66-3.61) and ZDV (0.89; 95% CI 0.53-1.47) were not
      associated with SGA versus TDF-(3TC/FTC)-EFV. CONCLUSIONS: Preconception TDF
      (3TC/FTC)-EFV and post-conception TDF-(3TC/FTC)-EFV were not associated with PTD
      or SGA, compared with other regimens. Increasing ART use merits further study of
      the optimum ART regimen for safe birth outcomes.

PMID- 29470509
TI  - Co-circulation of all the four dengue virus serotypes and detection of a novel
      clade of DENV-4 (genotype I) virus in Pune, India during 2016 season.
AB  - Dengue is the most common mosquito-borne viral infection in tropical and sub
      tropical countries. In recent years, India has reported increased incidences of
      concurrent infection with multiple serotypes of dengue viruses (DENV). In the
      present study, we have characterized DENV circulating during a single season of
      2016 in Pune, India. A total of 64 serum samples from NS1 ELISA positive dengue
      patients were used for PCR amplification of CprM region of the viral genome and
      sequencing. Phylogenetic analysis documented circulation of all the four DENV
      serotypes with predominance of DENV-2 (40.6%). DENV genotyping classified DENV-1
      to Genotype V, DENV-2 to Genotype IV, DENV-3 to Genotype III and DENV-4 to
      Genotype I. Further analysis revealed emergence of a novel clade (D) of genotype
      I of DENV-4. Subsequent isolation of three DENV-4 viruses in cell culture
      followed by complete genome sequence analysis confirmed this observation.
      Additionally, a new genotype within serotype-4 with >6.7% sequence variation from
      other genotypes was identified. This first report of significant co-circulation
      of all the four serotypes in a single outbreak in Pune reconfirms need for
      molecular monitoring of DENV.

PMID- 29470510
TI  - Impacts of the active layer on runoff in an upland permafrost basin, northern
      Tibetan Plateau.
AB  - The paucity of studies on permafrost runoff generation processes, especially in
      mountain permafrost, constrains the understanding of permafrost hydrology and
      prediction of hydrological responses to permafrost degradation. This study
      investigated runoff generation processes, in addition to the contribution of
      summer thaw depth, soil temperature, soil moisture, and precipitation to
      streamflow in a small upland permafrost basin in the northern Tibetan Plateau.
      Results indicated that the thawing period and the duration of the zero-curtain
      were longer in permafrost of the northern Tibetan Plateau than in the Arctic.
      Limited snowmelt delayed the initiation of surface runoff in the peat permafrost
      in the study area. The runoff displayed intermittent generation, with the
      duration of most runoff events lasting less than 24 h. Precipitation without
      runoff generation was generally correlated with lower soil moisture conditions.
      Combined analysis suggested runoff generation in this region was controlled by
      soil temperature, thaw depth, precipitation frequency and amount, and antecedent
      soil moisture. This study serves as an important baseline to evaluate future
      environmental changes on the Tibetan Plateau.

PMID- 29470511
TI  - Preliminary analysis of proteome alterations in non-aneurysmal, internal mammary
      artery tissue from patients with abdominal aortic aneurysms.
AB  - OBJECTIVE: The pathogenesis of abdominal aortic aneurysms (AAA) involves a
      disturbed balance of breakdown and buildup of arterial proteins. We envision that
      individuals with AAA carry generalized arterial protein alterations either
      because of effects of genetically or environmental AAA risk factors or because of
      compensatory changes due to signaling molecules released from the affected
      aneurysmal tissue. APPROACH: Protein extraction and quantitative proteome
      analysis by LC-MS/MS (liquid chromatography-mass spectrometry) was done on
      individual samples from the internal mammary artery from 11 individuals with AAA
      and 33 sex- and age-matched controls without AAA. Samples were selected from a
      biobank of leftover internal mammary arterial tissue gathered at coronary by-pass
      operations. RESULTS: We identified and quantitated 877 proteins, of which 44 were
      differentially expressed between the two groups (nominal p-values without
      correction for multiple testing). Some proteins related to the extracellular
      matrix displayed altered concentrations in the AAA group, particularly among
      elastin-related molecules [elastin, microfibrillar-associated protein 4 (MFAP4),
      lysyl oxidase]. In addition, several histones e.g. (e.g. HIST1H1E, HIST1H2BB) and
      other vascular cell proteins (e.g. versican, type VI collagen) were altered.
      CONCLUSIONS: Our results support the notion that generalized alterations occur in
      the arterial tree in patients with AAA. Elastin-related proteins and histones
      seem to be part of such changes, however these preliminary results require
      replication in an independent set of specimens and validation by functional
      studies.

PMID- 29470512
TI  - Association between HIV status and depressive symptoms among children and
      adolescents in the Southern Highlands Zone, Tanzania: A case-control study.
AB  - BACKGROUND: Children and adolescents continue to have HIV/AIDS in southern
      Saharan Africa. Scaling up of HIV services has significantly improved access to
      ARV and consequently improved on morbidity and mortality related to HIV/AIDS
      including opportunistic infection. Despite the above efforts, non-communicable
      conditions including mental disorders such as depression have been observed to
      contribute to the burden of disabilities about which little is documented. This
      study, therefore, aimed to determine the magnitude of depressive symptoms and the
      associated factors among HIV-infected children and adolescents. METHODS: The
      study was a matched case-control design involving 300 cases of HIV-infected
      children matched by age and sex against 600 uninfected controls. Systematic
      sampling technique was used to select the cases while multistage sampling
      technique was employed to identify villages/ streets purposive and sampling
      technique was employed to obtain participants from households. RESULTS: The
      overall prevalence of depressive symptoms among the cohort of 900 participants
      was found to be 12.9%, with 27% of HIV-infected and 5.8% of HIV-uninfected
      children and adolescents screened positive for depressive symptoms. Multiple
      logistic regression revealed that being HIV-infected (AOR 1.96(1.11-3.45)),
      residing in a rural setting (AOR 0.61(0.39-0.96)) and history of childhood
      deprivation (AOR 4.76 (2.79-8.13)) were significantly associated with depressive
      symptoms. CONCLUSION: HIV infected adolescents are more affected by depression
      compared to non-infected counterparts. Childhood deprivation was significantly
      associated with presence of depressive symptoms. Integration of mental health
      evaluation and treatment into the HIV care provided for adolescents can be
      beneficial. More studies to delineate factors associated with depressed
      adolescents with HIV may add value to the body of knowledge and overall
      improvement of care.

PMID- 29470515
TI  - Correction: Distinct temporal roles for the promyelocytic leukaemia (PML) protein
      in the sequential regulation of intracellular host immunity to HSV-1 infection.
AB  - [This corrects the article DOI: 10.1371/journal.ppat.1006769.].

PMID- 29470514
TI  - Profile of suicide attempts and risk factors among psychiatric patients: A case
      control study.
AB  - BACKGROUND: Suicidal behaviour remains challenging for clinicians to predict,
      with few established risk factors and warning signs among psychiatric patients.
      AIM: We aimed to describe characteristics and identify risk factors for suicide
      attempts among patients with psychiatric disorders. METHODS: Multivariable
      logistic regression analysis, adjusted for clinically important confounders, was
      employed to determine risk factors for suicide attempts within a psychiatric
      patient population. RESULTS: The case (n = 146) and control groups (n = 104) did
      not differ significantly with regards to sociodemographic characteristics. The
      majority of the participants who had attempted suicide did so with high intent to
      die, and expected to die without medical intervention. The primary method of
      attempt was pharmaceutical overdose among the case participants (73.3%). Results
      showed impulsivity (odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.03
      1.30) and borderline personality symptoms (OR = 1.07, 95% CI = 1.01-1.13) were
      significantly associated with attempted suicide. CONCLUSIONS: Our findings
      indicate that known sociodemographic risk factors for suicide may not apply
      within psychiatric populations. Prevention strategies for suicidal behaviour in
      psychiatric patients may be effective, including limited access to means for
      suicide attempts (i.e. excess pharmaceutical drugs) and target screening for high
      risk personality and impulsivity traits.

PMID- 29470513
TI  - Offspring sex impacts DNA methylation and gene expression in placentae from women
      with diabetes during pregnancy.
AB  - AIMS/HYPOTHESIS: We hypothesized that diabetes during pregnancy (DDP) alters
      genome-wide DNA methylation in placenta resulting in differentially methylated
      loci of metabolically relevant genes and downstream changes in RNA and protein
      expression. METHODS: We mapped genome-wide DNA methylation with the Infinium 450K
      Human Methylation Bead Chip in term fetal placentae from Native American and
      Hispanic women with DDP using a nested case-control design (n = 17 pairs). RNA
      expression and protein levels were assayed via RNA-Seq and Western Blot. RESULTS:
      Genome-wide DNA methylation analysis revealed 465 CpG sites with significant
      changes for male offspring, 247 for female offspring, and 277 for offspring of
      both sexes (p<0.001). Placentae from female offspring were 40% more likely to
      have significant gains in DNA methylation compared with placentae from male
      offspring exposed to DDP (p<0.001). Changes in DNA methylation corresponded to
      changes in RNA and protein levels for 6 genes: PIWIL3, CYBA, GSTM1, GSTM5, KCNE1
      and NXN. Differential DNA methylation was detected at loci related to
      mitochondrial function, DNA repair, inflammation, oxidative stress.
      CONCLUSIONS/INTERPRETATION: These findings begin to explain mechanisms
      responsible for the increased risk for obesity and type 2 diabetes in offspring
      of mothers with DDP.

PMID- 29470518
TI  - Universal scaling laws in metro area election results.
AB  - We explain the anomaly of election results between large cities and rural areas
      in terms of urban scaling in the 1948-2016 US elections and in the 2016 EU
      referendum of the UK. The scaling curves are all universal and depend on a single
      parameter only, and one of the parties always shows superlinear scaling and
      drives the process, while the sublinear exponent of the other party is merely the
      consequence of probability conservation. Based on the recently developed model of
      urban scaling, we give a microscopic model of voter behavior in which we replace
      diversity characterizing humans in creative aspects with social diversity and
      tolerance. The model can also predict new political developments such as the
      fragmentation of the left and the immigration paradox.

PMID- 29470516
TI  - Evaluation of diagnostic methods for the detection of intestinal schistosomiasis
      in endemic areas with low parasite loads: Saline gradient, Helmintex, Kato-Katz
      and rapid urine test.
AB  - BACKGROUND: In some tropical countries, such as Brazil, schistosomiasis control
      programs have led to a significant reduction in the prevalence and parasite
      burden of endemic populations. In this setting, the Kato-Katz technique, as the
      standard diagnostic method for the diagnosis of Schistosoma mansoni infections,
      which involves the analysis of two slides from one fecal sample, loses its
      sensitivity. As a result, a significant number of infected individuals are not
      detected. The objective of this study was to perform extensive parasitological
      testing of up to three fecal samples and include a rapid urine test (POC-CCA) in
      a moderate prevalence area in Northern Minas Gerais, Brazil, and evaluate the
      performance of each test separately and in combination. METHODS AND FINDINGS: A
      total of 254 individuals were examined with variants of the standard Kato-Katz
      technique (up to18 Kato-Katz slides prepared from three fecal samples), a
      modified Helmintex (30 g of feces), the saline gradient (500 mg of feces), and
      the POC-CCA methods. We established a reference standard taking into
      consideration all the positive results in any of the parasitological exams.
      Evaluation of the parasite burden by two Kato-Katz slides confirmed that most of
      the individuals harbored a light infection. When additional slides and different
      parasitological methods were included, the estimated prevalence rose 2.3 times,
      from 20.4% to 45.9%. The best sensitivity was obtained with the Helmintex method
      (84%). All parasitological methods readily detected a high or moderate intensity
      of infection; however, all lost their high sensitivity in the case of low or very
      low intensity infections. The overall sensitivity of POC-CCA (64.9%) was similar
      to the six Kato-Katz slides from three fecal samples. However, POC-CCA showed low
      concordance (kappa = 0.34) when compared with the reference standard.
      CONCLUSIONS: The recommended Kato-Katz method largely underestimated the
      prevalence of S. mansoni infection. Because the best performance was achieved
      with a modified Helmintex method, this technique might serve as a more precise
      reference standard. An extended number of Kato-Katz slides in combination with
      other parasitological methods or with POC-CCA was able to detect more than 80% of
      egg-positive individuals; however, the rapid urine test (POC-CCA) produced a
      considerable percentage of false positive results.

PMID- 29470519
TI  - Correction: Management of vertebral compression fracture in general practice:
      BEACH program.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0176351.].

PMID- 29470517
TI  - Two essential Thioredoxins mediate apicoplast biogenesis, protein import, and
      gene expression in Toxoplasma gondii.
AB  - Apicomplexan parasites are global killers, being the causative agents of diseases
      like toxoplasmosis and malaria. These parasites are known to be hypersensitive to
      redox imbalance, yet little is understood about the cellular roles of their
      various redox regulators. The apicoplast, an essential plastid organelle, is a
      verified apicomplexan drug target. Nuclear-encoded apicoplast proteins traffic
      through the ER and multiple apicoplast sub-compartments to their place of
      function. We propose that thioredoxins contribute to the control of protein
      trafficking and of protein function within these apicoplast compartments. We
      studied the role of two Toxoplasma gondii apicoplast thioredoxins (TgATrx), both
      essential for parasite survival. By describing the cellular phenotypes of the
      conditional depletion of either of these redox regulated enzymes we show that
      each of them contributes to a different apicoplast biogenesis pathway. We provide
      evidence for TgATrx1's involvement in ER to apicoplast trafficking and TgATrx2 in
      the control of apicoplast gene expression components. Substrate pull-down further
      recognizes gene expression factors that interact with TgATrx2. We use genetic
      complementation to demonstrate that the function of both TgATrxs is dependent on
      their disulphide exchange activity. Finally, TgATrx2 is divergent from human
      thioredoxins. We demonstrate its activity in vitro thus providing scope for drug
      screening. Our study represents the first functional characterization of
      thioredoxins in Toxoplasma, highlights the importance of redox regulation of
      apicoplast functions and provides new tools to study redox biology in these
      parasites.

PMID- 29470521
TI  - Correction: Correction: Do weaner pigs need in-feed antibiotics to ensure good
      health and welfare?
AB  - [This corrects the article DOI: 10.1371/journal.pone.0189434.].

PMID- 29470520
TI  - Association between expression of random gene sets and survival is evident in
      multiple cancer types and may be explained by sub-classification.
AB  - One of the goals of cancer research is to identify a set of genes that cause or
      control disease progression. However, although multiple such gene sets were
      published, these are usually in very poor agreement with each other, and very few
      of the genes proved to be functional therapeutic targets. Furthermore, recent
      findings from a breast cancer gene-expression cohort showed that sets of genes
      selected randomly can be used to predict survival with a much higher probability
      than expected. These results imply that many of the genes identified in breast
      cancer gene expression analysis may not be causal of cancer progression, even
      though they can still be highly predictive of prognosis. We performed a similar
      analysis on all the cancer types available in the cancer genome atlas (TCGA),
      namely, estimating the predictive power of random gene sets for survival. Our
      work shows that most cancer types exhibit the property that random selections of
      genes are more predictive of survival than expected. In contrast to previous
      work, this property is not removed by using a proliferation signature, which
      implies that proliferation may not always be the confounder that drives this
      property. We suggest one possible solution in the form of data-driven sub
      classification to reduce this property significantly. Our results suggest that
      the predictive power of random gene sets may be used to identify the existence of
      sub-classes in the data, and thus may allow better understanding of patient
      stratification. Furthermore, by reducing the observed bias this may allow more
      direct identification of biologically relevant, and potentially causal, genes.

PMID- 29470524
TI  - Correction: Predicting Hospitalised Paediatric Pneumonia Mortality Risk: An
      External Validation of RISC and mRISC, and Local Tool Development (RISC-Malawi)
      from Malawi.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0168126.].

PMID- 29470522
TI  - Quantification of edematous changes by diffusion magnetic resonance imaging in
      gastrocnemius muscles after spinal nerve ligation.
AB  - Patients with complex regional pain syndrome (CRPS) exhibit diverse symptoms,
      such as neuropathic pain, allodynia, local edema and skin color changes in the
      affected lesion. Although nerve injury may cause CRPS, pathophysiological
      mechanisms underlying the syndrome are unclear, and local edema, a characteristic
      of CRPS, has not been evaluated quantitatively for technical reasons. Here, using
      a rat spinal nerve ligation-induced CRPS model, we show that edematous changes in
      gastrocnemius muscle can be detected quantitatively by diffusion magnetic
      resonance imaging (MRI). Using the line-scan diffusion spectrum on a 1.5 T
      clinical MR imager, we demonstrate significant elevation of the apparent
      diffusion coefficient (ADC) ratios in gastrocnemius muscle on the ligated versus
      the sham-operated rats by one day after surgery, those ratios gradually decreased
      over time. Meanwhile, T2 ratios in gastrocnemius muscle on the ligated rats
      increased gradually and significantly, peaking two weeks after surgery, and those
      ratios remained high and were consistent with edema. Expression of vascular
      endothelial growth factor (VEGF), a key regulator of blood vessel formation and
      function, was significantly lower in gastrocnemius muscle on the ligated versus
      non-ligated side, suggesting that nerve ligation promotes edematous changes and
      perturbs VEGF expression in target muscle.

PMID- 29470523
TI  - A "late-but-fitter revertant cell" explains the high frequency of revertant
      mosaicism in epidermolysis bullosa.
AB  - Revertant mosaicism, or "natural gene therapy", is the phenomenon in which
      germline mutations are corrected by somatic events. In recent years, revertant
      mosaicism has been identified in all major types of epidermolysis bullosa, the
      group of heritable blistering disorders caused by mutations in the genes encoding
      epidermal adhesion proteins. Moreover, revertant mosaicism appears to be present
      in all patients with a specific subtype of recessive epidermolysis bullosa. We
      therefore hypothesized that revertant mosaicism should be expected at least in
      all patients with recessive forms of epidermolysis bullosa. Naturally corrected,
      patient-own cells are of extreme interest for their promising therapeutic
      potential, and their presence in all patients would open exciting, new treatment
      perspectives to those patients. To test our hypothesis, we determined the
      probability that single nucleotide reversions occur in patients' skin using a
      mathematical developmental model. According to our model, reverse mutations are
      expected to occur frequently (estimated 216x) in each patient's skin. Reverse
      mutations should, however, occur early in embryogenesis to be able to drive the
      emergence of recognizable revertant patches, which is expected to occur in only
      one per ~10,000 patients. This underestimate, compared to our clinical
      observations, can be explained by the "late-but-fitter revertant cell"
      hypothesis: reverse mutations arise at later stages of development, but provide
      revertant cells with a selective growth advantage in vivo that drives the
      development of recognizable healthy skin patches. Our results can be extrapolated
      to any other organ with stem cell division numbers comparable to skin, which may
      offer novel future therapeutic options for other genetic conditions if these
      revertant cells can be identified and isolated.

PMID- 29470525
TI  - Coral reef fishes exhibit beneficial phenotypes inside marine protected areas.
AB  - Human fishing effort is size-selective, preferentially removing the largest
      individuals from harvested stocks. Intensive, size-specific fishing mortality
      induces directional shifts in phenotypic frequencies towards the predominance of
      smaller and earlier-maturing individuals, which are among the primary causes of
      declining fish biomass. Fish that reproduce at smaller size and younger age
      produce fewer, smaller, and less viable larvae, severely reducing the
      reproductive capacity of harvested populations. Marine protected areas (MPAs) are
      extensively utilized in coral reefs for fisheries management, and are thought to
      mitigate the impacts of size-selective fishing mortality and supplement fished
      stocks through larval export. However, empirical evidence of disparities in
      fitness-relevant phenotypes between MPAs and adjacent fished reefs is necessary
      to validate this assertion. Here, we compare key life-history traits in three
      coral-reef fishes (Acanthurus nigrofuscus, Ctenochaetus striatus, and Parupeneus
      multifasciatus) between MPAs and fished reefs in the Philippines. Results of our
      analyses support previous hypotheses regarding the impacts of MPAs on phenotypic
      traits. Asymptotic length (Linf) and growth rates (K) differed between
      conspecifics in MPAs and fished reefs, with protected populations exhibiting
      phenotypes that are known to confer higher fecundity. Additionally, populations
      demonstrated increases in length at 50% maturity (L50) inside MPAs compared to
      adjacent areas, although age at 50% maturity (A50) did not appear to be impacted
      by MPA establishment. Shifts toward advantageous phenotypes were most common in
      the oldest and largest MPAs, but occurred in all of the MPAs examined. These
      results suggest that MPAs may provide protection against the impacts of size
      selective harvest on life-history traits in coral-reef fishes.

PMID- 29470527
TI  - Value of diagnostic and therapeutic laparoscopy for patients with blunt abdominal
      trauma: A 10-year medical center experience.
AB  - Laparoscopy has been used for the diagnosis and treatment for hemodynamically
      stable patients with penetrating abdominal trauma. This study evaluated whether
      diagnostic and therapeutic laparoscopy can be used as effectively in select
      patients with blunt abdominal trauma. All hemodynamically stable patients
      undergoing operations for blunt abdominal trauma over a 10-year period (2006
      2015) at a tertiary medical center were included. Patients undergoing laparotomy
      were categorized as group A. Patients who underwent laparoscopy were categorized
      as group B. The clinical outcomes of the 2 groups were compared. There were 139
      patients in group A and 126 patients in group B. Group A patients were more
      severely injured (mean injury severity score of 23.3 vs. 18.9, P < .001) and had
      a higher frequency of traumatic brain injuries (25.2% vs. 14.3%, P = .039). The
      sensitivity and specificity of diagnostic laparoscopy for patients in group B was
      99.1% and 100.0%, respectively. No non-therapeutic laparotomies were performed in
      group B, and the success rate of therapeutic laparoscopy was 92.0% (103/112) for
      patients with significant intra-abdominal injuries. Patients in the 2 groups had
      similar perioperative and postoperative outcomes in terms of operation times,
      blood loss, blood transfusion requirements, mortality, and complications (all, P
      > .05). Laparoscopy is a feasible and safe tool for the diagnosis and treatment
      of hemodynamically stable patients with blunt abdominal trauma who require
      surgery.

PMID- 29470526
TI  - Expression of Yin Yang 1 in cervical cancer and its correlation with E-cadherin
      expression and HPV16 E6.
AB  - The molecular mechanisms of normal cervical squamous epithelium advancing to
      cervical intraepithelial neoplasia (CIN) and eventually to cervical squamous cell
      carcinoma (CSCC) are largely unknown. This study explored abnormal expression of
      Yin Yang 1 (YY1) in cervical cancer and its correlation with the expression of E
      cadherin and human papillomavirus (HPV) 16 E6. YY1, E-cadherin and HPV16 E6
      expression were detected by immunohistochemistry in 90 cervical tissue specimens
      collected from 30 patients with hysteromyoma, 15 patients with CIN I, 15 patients
      with CIN II-III, and 30 patients with CSCC. The H-score method was employed to
      measure the expression of YY1, E-cadherin and HPV16 E6. Increased expression of
      YY1 and HPV16 E6, and the decreased expression levels of E-cadherin were strongly
      associated with malignant transformation of the cervical epithelium and the
      histological progression of CSCC. The expression of YY1 in cervical tissues was
      inversely correlated with E-cadherin expression, and positively correlated with
      HPV16 E6 expression. Expression of YY1 in CSCC tissues was not significantly
      correlated with tumor differentiation, but was significantly correlated with an
      advanced clinical stage of CSCC. These results suggest that up-regulation of YY1
      is closely associated with the progression of CSCC, and YY1 may play an important
      role in the pathogenesis of cervical cancer by modulating the expression of E
      cadherin and HPV16 E6.

PMID- 29470528
TI  - Linear relationship between peak and season-long abundances in insects.
AB  - An accurate quantitative relationship between key characteristics of an insect
      population, such as season-long and peak abundances, can be very useful in pest
      management programs. To the best of our knowledge, no such relationship has yet
      been established. Here we establish a predictive linear relationship between
      insect catch Mpw during the week of peak abundance, the length of seasonal flight
      period, F (number of weeks) and season-long cumulative catch (abundance) A =
      0.41MpwF. The derivation of the equation is based on several general assumptions
      and does not involve fitting to experimental data, which implies generality of
      the result. A quantitative criterion for the validity of the model is presented.
      The equation was tested using extensive data collected on captures of male gypsy
      moths Lymantria dispar (L.) (Lepidoptera: Erebidae) in pheromone-baited traps
      during 15 years. The model was also tested using trap catch data for two species
      of mosquitoes, Culex pipiens (L.) (Diptera: Culicidae) and Aedes albopictus
      (Skuse) (Diptera: Culicidae), in Gravid and BG-sentinel mosquito traps,
      respectively. The simple, parameter-free equation approximates experimental data
      points with relative error of 13% and R2 = 0.997, across all of the species
      tested. For gypsy moth, we also related season-long and weekly trap catches to
      the daily trap catches during peak flight. We describe several usage scenarios,
      in which the derived relationships are employed to help link results of small
      scale field studies to the operational pest management programs.

PMID- 29470529
TI  - Xenopus: An alternative model system for identifying muco-active agents.
AB  - The airway epithelium in human plays a central role as the first line of defense
      against environmental contaminants. Most respiratory diseases such as chronic
      obstructive pulmonary disease (COPD), asthma, and respiratory infections, disturb
      normal muco-ciliary functions by stimulating the hypersecretion of mucus. Several
      muco-active agents have been used to treat hypersecretion symptoms in patients.
      Current muco-active reagents control mucus secretion by modulating either airway
      inflammation, cholinergic parasympathetic nerve activities or by reducing the
      viscosity by cleaving crosslinking in mucin and digesting DNAs in mucus. However,
      none of the current medication regulates mucus secretion by directly targeting
      airway goblet cells. The major hurdle for screening potential muco-active agents
      that directly affect the goblet cells, is the unavailability of in vivo model
      systems suitable for high-throughput screening. In this study, we developed a
      high-throughput in vivo model system for identifying muco-active reagents using
      Xenopus laevis embryos. We tested mucus secretion under various conditions and
      developed a screening strategy to identify potential muco-regulators. Using this
      novel screening technique, we identified narasin as a potential muco-regulator.
      Narasin treatment of developing Xenopus embryos significantly reduced mucus
      secretion. Furthermore, the human lung epithelial cell line, Calu-3, responded
      similarly to narasin treatment, validating our technique for discovering muco
      active reagents.

PMID- 29470530
TI  - Effectiveness of health education intervention in improving knowledge, attitude,
      and practices regarding Tuberculosis among HIV patients in General Hospital
      Minna, Nigeria - A randomized control trial.
AB  - INTRODUCTION: The risk of development of active TB in HIV-infected individuals is
      20-37 times higher than those that are HIV negative. Poor knowledge of TB amongst
      people living with HIV has been associated with high transmission. OBJECTIVES: To
      determine the effectiveness of a new health education intervention module in
      improving knowledge, attitude, and practice (KAP) regarding tuberculosis among
      HIV patients in General Hospital Minna, Nigeria. METHODS: A randomized control
      trial was carried out from July 2015 to June 2017. A random number generating
      program was used to allocate 226 respondents into 2 groups. The intervention
      group received health education regarding tuberculosis using the developed
      module. The control group received the normal services provided for HIV patients.
      Data were collected from December 2015 to September 2016 at baseline, immediate
      post intervention, three, six and nine months. The outcome measures were
      knowledge, attitude, and practice. RESULTS: There was no significant difference
      with respect to socio-demographic characteristics, KAP of the respondents in the
      intervention and control group at baseline. However, there was significant
      improvement in knowledge in the intervention group compared to the control group,
      group main effect (F = (1,218) = 665.889, p = 0.001, partial ?2 = 0.753, d =
      5.4); time (F = (3.605, 218) = 52.046, p = 0.001, partial ?2 = 0.193, d = 1.52)
      and interaction between group with time (F = (3.605, 218) = 34.028, p = 0.001,
      partial ?2 = 0.135, d = 1.23). Likewise, there was significant improvement in
      attitude, group main effect (p = 0.001, d = 1.26) and time (p = 0.001, p, d =
      0.65). Similarly, there was improvement in practice, group main effect, time, and
      interaction of group with time (p < 0.05). CONCLUSION: The health education
      intervention program was effective in improving KAP regarding tuberculosis among
      HIV patients.

PMID- 29470531
TI  - Epidemiology and risk factors of extensively drug-resistant Pseudomonas
      aeruginosa infections.
AB  - BACKGROUND: The incidence of nosocomial infections from extensively drug
      resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide. We
      investigated the prevalence and factors associated with XDR-PA infections,
      including the factors that predict mortality. METHODS: We retrospectively studied
      a cohort of adult, hospitalized patients with P. aeruginosa (PA) infections
      between April and December 2014. RESULTS: Of the 255 patients with PA infections,
      56 (22%) were due to XDR-PA, 32 (12.5%) to multidrug resistant Pseudomonas
      aeruginosa (MDR-PA), and 167 (65.5%) to non-MDR PA. Receiving total parenteral
      nutrition (adjusted OR [aOR] 6.21; 95% CI 1.05-36.70), prior carbapenem use (aOR
      4.88; 95% CI 2.36-10.08), and prior fluoroquinolone use (aOR 3.38; 95% CI 1.44
      7.97) were independently associated with the XDR-PA infections. All XDR-PA
      remained susceptible to colistin. Factors associated with mortality attributable
      to the infections were the presence of sepsis/septic shock (aOR 11.60; 95% CI
      4.66-28.82), admission to a medical department (aOR 4.67; 95% CI 1.81-12.06),
      receiving a central venous catheter (aOR 3.78; 95% CI 1.50-9.57), and XDR-PA
      infection (aOR 2.73; 95% CI 1.05-7.08). CONCLUSION: The prevalence of XDR-PA
      infections represented almost a quarter of Pseudomonas aeruginosa hospital
      acquired infections and rendered a higher mortality. The prompt administration of
      an appropriate empirical antibiotic should be considered when an XDR-PA infection
      is suspected.

PMID- 29470532
TI  - Psychosocial health and suicidal ideation among people living with HIV/AIDS: A
      cross-sectional study in Nanjing, China.
AB  - BACKGROUND: Suicide is a serious cause of mortality worldwide and is considered
      as a psychiatric emergency. People living with HIV/AIDS (PLWHA) have higher rates
      of suicidal behavior than the general population. This study assessed the
      prevalence and verified the syndemic effect of psychosocial health conditions on
      suicidal ideation among PLWHA in China. METHODS: An institutional-based cross
      sectional study was conducted from July to August 2016 in Nanjing, China, using a
      self-report questionnaire. Sociodemographic characteristics, infection status,
      psychosocial variables and suicide ideation reports of participants were
      collected. Logistic regressions were used to identify potential factors
      associated with suicidal ideation and to verify the syndemic effect of
      psychosocial factors. Additionally, odds ratios (ORs) with 95% confidence
      intervals (95% CI) were computed. RESULTS: In total, four hundred sixty-five
      PLWHA participated, 31.6% (n = 147) of whom had suicidal ideation. The results
      from univariate analysis showed that older age, low education level, being
      married, having children, and psychosocial variables (high perceived stigma,
      depression, low self-esteem, social support and resilience) were significantly
      associated with increased suicidal ideation. Multiple logistic regression models
      revealed that depression (OR = 2.70, 95%CI = 1.62-4.51), perceived stigma (OR =
      1.97, 95%CI = 1.17-3.32), and low social support (OR = 1.85, 95%CI = 1.08-3.20)
      and self-esteem (OR = 4.11, 95%CI = 2.06-8.16) were statistically significant.
      PLWHA with at least two psychosocial health problems were nearly 5 times more
      likely (OR = 4.72, 95% CI 3.11-7.17) to have had suicidal ideation. CONCLUSIONS:
      Suicidal ideation is frequent among PLWHA in China and is consistent with
      prevalence estimates from abroad. Psychosocial health problems were the
      determining factors associated with suicidal ideation, and a syndemic effect of
      psychosocial health conditions was confirmed in predicting suicidal ideation.
      Therefore, early screening of high-risk groups for suicidal ideation and more
      psychosocial health care among PLWHA are needed.

PMID- 29470533
TI  - Human antibody recognition of antigenic site IV on Pneumovirus fusion proteins.
AB  - Respiratory syncytial virus (RSV) is a major human pathogen that infects the
      majority of children by two years of age. The RSV fusion (F) protein is a primary
      target of human antibodies, and it has several antigenic regions capable of
      inducing neutralizing antibodies. Antigenic site IV is preserved in both the pre
      fusion and post-fusion conformations of RSV F. Antibodies to antigenic site IV
      have been described that bind and neutralize both RSV and human metapneumovirus
      (hMPV). To explore the diversity of binding modes at antigenic site IV, we
      generated a panel of four new human monoclonal antibodies (mAbs) and competition
      binding suggested the mAbs bind at antigenic site IV. Mutagenesis experiments
      revealed that binding and neutralization of two mAbs (3M3 and 6F18) depended on
      arginine (R) residue R429. We discovered two R429-independent mAbs (17E10 and
      2N6) at this site that neutralized an RSV R429A mutant strain, and one of these
      mAbs (17E10) neutralized both RSV and hMPV. To determine the mechanism of cross
      reactivity, we performed competition-binding, recombinant protein mutagenesis,
      peptide binding, and electron microscopy experiments. It was determined that the
      human cross-reactive mAb 17E10 binds to RSV F with a binding pose similar to
      101F, which may be indicative of cross-reactivity with hMPV F. The data presented
      provide new concepts in RSV immune recognition and vaccine design, as we describe
      the novel idea that binding pose may influence mAb cross-reactivity between RSV
      and hMPV. Characterization of the site IV epitope bound by human antibodies may
      inform the design of a pan-Pneumovirus vaccine.

PMID- 29470534
TI  - The effect of isohydric hemodialysis on the binding and removal of uremic
      retention solutes.
AB  - BACKGROUND: There is growing evidence that the accumulation of protein- bound
      uremic retention solutes, such as indoxyl sulfate, p-cresyl sulfate and kynurenic
      acid, play a role in the accelerated cardiovascular disease seen in patients
      undergoing chronic hemodialysis. Protein-binding, presumably to albumin, renders
      these solutes poor-dialyzable. We previously observed that the free fraction of
      indoxyl sulfate was markedly reduced at the end of hemodialysis. We hypothesized
      that solute binding might be pH-dependent and attributed the changes in free
      solute concentration to the higher serum pH observed at the end of standard
      hemodialysis with dialysis buffer bicarbonate concentration greater than 35
      mmol/L. We observed that acidification of uremic plasma to pH 6 in vitro greatly
      increased the proportion of freeIS. METHODS: We tested our hypothesis by reducing
      the dialysate bicarbonate buffer concentration to 25 mmol/L for the initial half
      of the hemodialysis treatment ("isohydric dialysis"). Eight stable hemodialysis
      patients underwent "isohydric dialysis" for 90 minutes and then were switched to
      standard buffer (bicarbonate = 37mmol/L). A second dialysis, 2 days later,
      employed standard buffer throughout. RESULTS: We found a clearcut separation of
      blood pH and bicarbonate concentrations after 90 minutes of "isohydric dialysis"
      (pH = 7.37, bicarbonate = 22.4 mmol/L) and standard dialysis (pH = 7.49,
      bicarbonate = 29.0 mmol/L). Binding affinity varied widely among the 10 uremic
      retention solutes analyzed. Kynurenic acid (0.05 free), p-cresyl sulfate (0.12
      free) and indoxyl sulfate (0.13 free) demonstrated the greatest degree of
      binding. Three solutes (indoxyl glucuronide, p-cresyl glucuronide, and phenyl
      glucuronide) were virtually unbound. Analysis of free and bound concentrations of
      uremic retention solutes confirmed our prediction that binding of solute is
      affected by pH. However, in a mixed models analysis, we found that the reduction
      in total uremic solute concentration during dialysis accounted for a greater
      proportion of the variation in free concentration, presumably an effect of
      saturation binding to albumin, than did the relatively small change in pH
      produced by isohydric dialysis. The effect of pH on binding appeared to be
      restricted to those solutes most highly protein-bound. The solutes most tightly
      bound exhibited the lowest dialyzer clearances. An increase in dialyzer clearance
      during isohydric and standard dialyses was statistically significant only for
      kynurenic acid. CONCLUSION: These findings provide evidence that the binding of
      uremic retention solutes is influenced by pH. The effect of reducing buffer
      bicarbonate concentration ("isohydric dialysis:"), though significant, was small
      but may be taken to suggest that further modification of dialysis technique that
      would expose blood to a greater decrease in pH would lead to a greater increase
      the free fraction of solute and enhance the efficacy of hemodialysis in the
      removal of highly protein-bound uremic retention solutes.

PMID- 29470535
TI  - Body configuration at first stepping-foot contact predicts backward balance
      recovery capacity in people with chronic stroke.
AB  - OBJECTIVE: To determine the predictive value of leg and trunk inclination angles
      at stepping-foot contact for the capacity to recover from a backward balance
      perturbation with a single step in people after stroke. METHODS: Twenty-four
      chronic stroke survivors and 21 healthy controls were included in a cross
      sectional study. We studied reactive stepping responses by subjecting
      participants to multidirectional stance perturbations at different intensities on
      a translating platform. In this paper we focus on backward perturbations.
      Participants were instructed to recover from the perturbations with maximally one
      step. A trial was classified as 'success' if balance was restored according to
      this instruction. We recorded full-body kinematics and computed: 1) body
      configuration parameters at first stepping-foot contact (leg and trunk
      inclination angles) and 2) spatiotemporal step parameters (step onset, step
      length, step duration and step velocity). We identified predictors of balance
      recovery capacity using a stepwise logistic regression. Perturbation intensity
      was also included as a predictor. RESULTS: The model with spatiotemporal
      parameters (perturbation intensity, step length and step duration) could
      correctly classify 85% of the trials as success or fail (Nagelkerke R2 = 0.61).
      In the body configuration model (Nagelkerke R2 = 0.71), perturbation intensity
      and leg and trunk angles correctly classified the outcome of 86% of the recovery
      attempts. The goodness of fit was significantly higher for the body configuration
      model compared to the model with spatiotemporal variables (p<0.01). Participant
      group and stepping leg (paretic or non-paretic) did not significantly improve the
      explained variance of the final body configuration model. CONCLUSIONS: Body
      configuration at stepping-foot contact is a valid and clinically feasible
      indicator of backward fall risk in stroke survivors, given its potential to be
      derived from a single sagittal screenshot.

PMID- 29470536
TI  - Metastatic site as a predictor of nivolumab efficacy in patients with advanced
      non-small cell lung cancer: A retrospective multicenter trial.
AB  - PURPOSE: To conduct a retrospective multicenter trial to determine the
      significance of metastatic site as a predictor of nivolumab efficacy in patients
      with advanced non-small cell lung cancer. METHODS: This study was conducted
      across three medical centers in Japan. We retrospectively reviewed all patients
      who commenced nivolumab treatment at these centers between December 17, 2015 and
      July 31, 2016. Clinical data were collected, including age, sex, smoking status,
      Eastern Cooperative Oncology Group performance status, and metastatic site (lymph
      nodes, liver, brain, bone, lungs [intrapulmonary metastasis], and malignant
      pleural effusion) at the time of commencing nivolumab treatment. Patients were
      followed-up until March 31, 2017. RESULTS: Two hundred and one patients were
      enrolled. The median age at the time of commencing nivolumab treatment was 68
      (range, 27-87) years. One hundred and thirty-five patients were male, 157
      patients had a history of smoking, 153 patients had a performance status of 0-1,
      and 42 patients had squamous cell carcinoma. The median progression-free survival
      of all patients was 2.5 months. In the univariate analysis, a performance status
      of >=2 (hazard ratio [HR]: 1.89, 95.0% confidence interval [CI]: 1.33-2.69; p <
      0.001) and liver (HR: 2.09, 95.0% CI: 1.35-3.25; p < 0.001) and lung (HR: 1.57,
      95.0% CI: 1.14-2.16; p < 0.01) metastases correlated with a significantly shorter
      progression-free survival in nivolumab-treated patients. In the multivariate
      analysis, a performance status of >=2 (HR: 1.54, 95.0% CI: 1.05-2.25; p < 0.05)
      and liver (HR: 1.90, 95.0% CI: 1.21-2.98; p < 0.01) and lung (HR: 1.41, 95.0% CI:
      1.00-1.99; p < 0.05) metastases were independently correlated with a
      significantly shorter progression-free survival in nivolumab-treated patients.
      CONCLUSION: Liver and lung metastases and a poor performance status are
      independent predictors of nivolumab efficacy in patients with advanced non-small
      cell lung cancer.

PMID- 29470538
TI  - Correction: Diverse Gastropod Hosts of Angiostrongylus cantonensis, the Rat
      Lungworm, Globally and with a Focus on the Hawaiian Islands.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0094969.].

PMID- 29470537
TI  - Microsomal prostaglandin E synthase-1 gene deletion impairs neuro-immune
      circuitry of the cholinergic anti-inflammatory pathway in endotoxaemic mouse
      spleen.
AB  - The cholinergic anti-inflammatory pathway (CAP) is an innate neural reflex where
      parasympathetic and sympathetic nerves work jointly to control inflammation.
      Activation of CAP by vagus nerve stimulation (VNS) has paved way for novel
      therapeutic strategies in treating inflammatory diseases. Recently, we discovered
      that VNS mediated splenic acetylcholine (ACh) release and subsequent
      immunosuppression in response to LPS associated inflammation is impaired in mice
      lacking microsomal prostaglandin E synthase-1 (mPGES-1) expression, a key enzyme
      responsible for prostaglandin E2 synthesis. Here, we have further investigated
      the consequences of mPGES-1 deficiency on various molecular/cellular events in
      the spleen which is critical for the optimal functioning of VNS in endotoxaemic
      mice. First, VNS induced splenic norepinephrine (NE) release in both mPGES-1
      (+/+) and (-/-) mice. Compared to mPGES-1 (+/+), immunomodulatory effects of NE
      on cytokines were strongly compromised in mPGES-1 (-/-) splenocytes.
      Interestingly, while LPS increased choline acetyltransferase (ChAT) protein level
      in mPGES-1 (+/+) splenocytes, it failed to exert similar effects in mPGES-1 (-/-)
      splenocytes despite unaltered beta2 AR protein expression. In addition, nicotine
      inhibited TNFalpha release by LPS activated mPGES-1 (+/+) splenocytes in vitro.
      However, such immunosuppressive effects of nicotine were reversed both in mPGES-1
      (-/-) mouse splenocytes and human PBMC treated with mPGES-1 inhibitor. In
      summary, our data implicate PGE2 as an important mediator of ACh synthesis and
      noradrenergic/cholinergic molecular events in the spleen that constitute a
      crucial part of the CAP immune regulation. Our results suggest a possible link
      between cholinergic and PG system of CAP that may be of clinical significance in
      VNS treatment.

PMID- 29470539
TI  - Divergence in male sexual odor signal and genetics across populations of the red
      mason bee, Osmia bicornis, in Europe.
AB  - In some insect species, females may base their choice for a suitable mate on male
      odor. In the red mason bee, Osmia bicornis, female choice is based on a male's
      odor bouquet as well as its thorax vibrations, and its relatedness to the female,
      a putative form of optimal outbreeding. Interestingly, O. bicornis can be found
      as two distinct color morphs in Europe, which are thought to represent subspecies
      and between which we hypothesize that female discrimination may be particularly
      marked. Here we investigated (i) if these two colors morphs do indeed represent
      distinct, reproductively differentiated populations, (ii) how odor bouquets of
      male O. bicornis vary within and between populations, and (iii) whether variation
      in male odor correlates with genetic distance, which might represent a cue by
      which females could optimally outbreed. Using GC and GC-MS analysis of male odors
      and microsatellite analysis of males and females from 9 populations, we show
      that, in Denmark, an area of subspecies sympatry, the two color morphs at any one
      site do not differ, either in odor bouquet or in population genetic
      differentiation. Yet populations across Europe are distinct in their odor profile
      as well as being genetically differentiated. Odor differences do not, however,
      mirror genetic differentiation between populations. We hypothesize that
      populations from Germany, England and Denmark may be under sexual selection
      through female choice for local odor profiles, which are not related to color
      morph though which could ultimately lead to population divergence and speciation.

PMID- 29470540
TI  - A-674563, a putative AKT1 inhibitor that also suppresses CDK2 activity, inhibits
      human NSCLC cell growth more effectively than the pan-AKT inhibitor, MK-2206.
AB  - AKT is a serine-threonine kinase implicated in tumorigenesis as a central
      regulator of cellular growth, proliferation, survival, and metabolism. Activated
      AKT is commonly overexpressed in non-small cell lung cancer (NSCLC) and
      accordingly AKT inhibitors are under clinical investigation for NSCLC treatment.
      Thus far, the AKT inhibitors being evaluated broadly target all three (1-3) AKT
      isoforms but recent evidence suggests opposing roles in lung tumorigenesis where
      loss of Akt1 inhibits while the loss of Akt2 enhances lung tumor development.
      Based on these findings, we hypothesized that selective inhibition of AKT-1 would
      be a more effective therapeutic strategy than pan-AKT inhibition for NSCLC
      treatment. Using six NSCLC cell lines, we found that the AKT-1 inhibitor, A
      674563, was significantly more effective at reducing NSCLC cell survival relative
      to the pan-AKT inhibitor MK-2206. Comparison of the downstream effects of the
      inhibitors suggests that altered cell cycle progression and off-target CDK2
      inhibition are likely vital to the improved efficacy of A-674563 over MK-2206.

PMID- 29470541
TI  - RNA 3-dimensional structural motifs as a critical constraint of viroid RNA
      evolution.

PMID- 29470542
TI  - Functional fine-tuning between bacterial DNA recombination initiation and quality
      control systems.
AB  - Homologous recombination (HR) is crucial for the error-free repair of DNA double
      strand breaks (DSBs) and the restart of stalled replication. However, imprecise
      HR can lead to genome instability, highlighting the importance of HR quality
      control. After DSB formation, HR proceeds via DNA end resection and recombinase
      loading, whereas helicase-catalyzed disruption of a subset of subsequently formed
      DNA invasions is thought to be essential for maintaining HR accuracy via
      inhibiting illegitimate (non-allelic) recombination. Here we show that in vitro
      characterized mechanistic aberrations of E. coli RecBCD (resection and
      recombinase loading) RecQ (multifunctional DNA-restructuring helicase) mutant
      enzyme variants, on one hand, cumulatively deteriorate cell survival under
      certain conditions of genomic stress. On the other hand, we find that RecBCD and
      RecQ defects functionally compensate each other in terms of HR accuracy. The
      abnormally long resection and unproductive recombinase loading activities of a
      mutant RecBCD complex (harboring the D1080A substitution in RecB) cause enhanced
      illegitimate recombination. However, this compromised HR-accuracy phenotype is
      suppressed in double mutant strains harboring mutant RecQ variants with
      abnormally enhanced helicase and inefficient invasion disruptase activities.
      These results frame an in vivo context for the interplay of biochemical
      activities leading to illegitimate recombination, and underscore its long-range
      genome instability effects manifest in higher eukaryotes.

PMID- 29470543
TI  - Translational autoregulation of BZW1 and BZW2 expression by modulating the
      stringency of start codon selection.
AB  - The efficiency of start codon selection during ribosomal scanning in eukaryotic
      translation initiation is influenced by the context or flanking nucleotides
      surrounding the AUG codon. The levels of eukaryotic translation initiation
      factors 1 (eIF1) and 5 (eIF5) play critical roles in controlling the stringency
      of translation start site selection. The basic leucine zipper and W2 domain
      containing proteins 1 and 2 (BZW1 and BZW2), also known as eIF5-mimic proteins,
      are paralogous human proteins containing C-terminal HEAT domains that resemble
      the HEAT domain of eIF5. We show that translation of mRNAs encoding BZW1 and BZW2
      homologs in fungi, plants and metazoans is initiated by AUG codons in conserved
      unfavorable initiation contexts. This conservation is reminiscent of the
      conserved unfavorable initiation context that enables autoregulation of EIF1. We
      show that overexpression of BZW1 and BZW2 proteins enhances the stringency of
      start site selection, and that their poor initiation codons confer autoregulation
      on BZW1 and BZW2 mRNA translation. We also show that overexpression of these two
      proteins significantly diminishes the effect of overexpressing eIF5 on stringency
      of start codon selection, suggesting they antagonize this function of eIF5. These
      results reveal a surprising role for BZW1 and BZW2 in maintaining homeostatic
      stringency of start codon selection, and taking into account recent biochemical,
      genetic and structural insights into eukaryotic initiation, suggest a model for
      BZW1 and BZW2 function.

PMID- 29470544
TI  - Validation of the What Matters Index: A brief, patient-reported index that guides
      care for chronic conditions and can substitute for computer-generated risk
      models.
AB  - INTRODUCTION: Current health care delivery relies on complex, computer-generated
      risk models constructed from insurance claims and medical record data. However,
      these models produce inaccurate predictions of risk levels for individual
      patients, do not explicitly guide care, and undermine health management
      investments in many patients at lesser risk. Therefore, this study prospectively
      validates a concise patient-reported risk assessment that addresses these
      inadequacies of computer-generated risk models. METHODS: Five measures with well
      documented impacts on the use of health services are summed to create a "What
      Matters Index." These measures are: 1) insufficient confidence to self-manage
      health problems, 2) pain, 3) bothersome emotions, 4) polypharmacy, and 5) adverse
      medication effects. We compare the sensitivity and predictive values of this
      index with two representative risk models in a population of 8619 Medicaid
      recipients. RESULTS: The patient-reported "What Matters Index" and the
      conventional risk models are found to exhibit similar sensitivities and
      predictive values for subsequent hospital or emergency room use. The "What
      Matters Index" is also reliable: akin to its performance during development, for
      patients with index scores of 1, 2, and >=3, the odds ratios (with 95% confidence
      intervals) for subsequent hospitalization within 1 year, relative to patients
      with a score of 0, are 1.3 (1.1-1.6), 2.0 (1.6-2.4), and 3.4 (2.9-4.0),
      respectively; for emergency room use, the corresponding odds ratios are 1.3 (1.1
      1.4), 1.9 (1.6-2.1), and 2.9 (2.6-3.3). Similar findings were replicated among
      smaller populations of 1061 mostly older patients from nine private practices and
      4428 Medicaid patients without chronic conditions. SUMMARY: In contrast to
      complex computer-generated risk models, the brief patient-reported "What Matters
      Index" immediately and unambiguously identifies fundamental, remediable needs for
      each patient and more sensibly directs the delivery of services to patient
      categories based on their risk for subsequent costly care.

PMID- 29470545
TI  - Private healthcare provider experiences with social health insurance schemes:
      Findings from a qualitative study in Ghana and Kenya.
AB  - BACKGROUND: Incorporating private healthcare providers into social health
      insurance schemes is an important means towards achieving universal health
      coverage in low and middle income countries. However, little research has been
      conducted about why private providers choose to participate in social health
      insurance systems in such contexts, or their experiences with these systems. We
      explored private providers' perceptions of and experiences with participation in
      two different social health insurance schemes in Sub-Saharan Africa-the National
      Health Insurance Scheme (NHIS) in Ghana and the National Hospital Insurance Fund
      (NHIF) in Kenya. METHODS: In-depth interviews were held with providers working at
      79 facilities of varying sizes in three regions of Kenya (N = 52) and three
      regions of Ghana (N = 27). Most providers were members of a social franchise
      network. Interviews covered providers' reasons for (non) enrollment in the health
      insurance system, their experiences with the accreditation process, and benefits
      and challenges with the system. Interviews were coded in Atlas.ti using an open
      coding approach and analyzed thematically. RESULTS: Most providers in Ghana were
      NHIS-accredited and perceived accreditation to be essential to their businesses,
      despite challenges they encountered due to long delays in claims reimbursement.
      In Kenya, fewer than half of providers were NHIF-accredited and several said that
      their clientele were not NHIF enrolled. Understanding of how the NHIF functioned
      was generally low. The lengthy and cumbersome accreditation process also emerged
      as a major barrier to providers' participation in the NHIF in Kenya, but the NHIS
      accreditation process was not a major concern for providers in Ghana.
      CONCLUSIONS: In expanding social health insurance, coordinated efforts are needed
      to increase coverage rates among underserved populations while also accrediting
      the private providers who serve those populations. Market pressure was a key
      force driving providers to gain and maintain accreditation in both countries.
      Developing mechanisms to engage private providers as stakeholders in social
      health insurance schemes is important to incentivizing their participation and
      addressing their concerns.

PMID- 29470546
TI  - Computer simulations reveal changes in the conformational space of the
      transcriptional regulator MosR upon the formation of a disulphide bond and in the
      collective motions that regulate its DNA-binding affinity.
AB  - M. tuberculosis oxidation sense Regulator (MosR) is a transcriptional regulator
      from Mycobacterium tuberculosis. It senses the environment oxidation and
      regulates the expression of a secreted oxidoreductase, thus defending the bacilli
      against oxidative stress from the phagosome. While most of the members of the
      Multiple antibiotics resistance Regulator (MarR) family are ligand-responsive,
      MosR may dissociate from its DNA site upon formation of an intrachain disulphide
      bond. However, the structure of MosR in its oxidized state is not known, and it
      is not clear how the formation of this disulphide bond would lead to the
      conformational changes required for dissociation of the DNA. Nonetheless, MosR
      presents two crystallographically resolved conformations in its reduced state:
      bound and unbound to DNA. We managed to simulate MosR unbound to the DNA, both in
      the presence and in the absence of the disulphide bond. Our results indicate that
      this disulphide bond precludes the N-terminal residues from adopting a
      conformation that stands in-between the helix alpha1 and the DNA binding domain
      (DBD) from the other chain. Once this conformation is achieved in the reduced
      state, this DBD detaches from the dimerization domain and becomes more flexible,
      being able to perform motions with higher amplitude and higher degree of
      collectivity. Only then, MosR may achieve a conformation where its recognition
      helices fit into the major grooves of its DNA site. The analysis of the
      collective motions performed by MosR, during the different situations sampled by
      the molecular dynamics (MDs), was only possible by the method of filtering
      harmonic modes with specific frequencies. The frequency of the collective motions
      performed by the DBD of MosR in the reduced state to achieve a DNA-binding
      conformation is in the range of 20 to 50 MHz, but it may be associated to more
      sporadic events since it requires the combination of a suitable conformation of
      the N-terminal residues.

PMID- 29470547
TI  - The characteristics of residents with unawareness of hepatitis C virus infection
      in community.
AB  - BACKGROUND: Control of hepatitis C virus infection (HCV) is an increasingly
      important issue. Enhancing screening coverage is necessary to discover more HCV
      infected subjects in community. However, a substantial population is unaware of
      HCV infection that needs more attention. AIM: The aims of this study were to
      evaluate the status of HCV infected residents in remote villages, to compare
      characteristics between already known and unaware HCV infection subjects, and to
      analyze the disease insights. PATIENTS AND METHODS: Screening intervention for
      liver diseases was conducted in remote villages of Tainan City of southern Taiwan
      from August 2014 to July 2016. Items of screening examinations included
      questionnaire, blood sampling for liver tests and viral hepatitis markers
      (hepatitis B surface antigen and anti-HCV antibody), abdominal sonography survey,
      and liver stiffness measurement by transient elastography. Quantitation of HCV
      RNA was measured for residents with positive anti-HCV antibody. RESULTS: A total
      of 194 (13.5%) out of 1439 participants showed positive for anti-HCV antibody.
      HCV viremia was detected in 119 (61.3%) residents. Previously unaware HCV
      infection by questionnaire record was present in 68 (35.1%) of ant-HCV positive
      residents. By multivariate logistic analysis, unaware HCV infected residents
      exhibited significantly mild liver fibrosis (OR 0.876, 95% CI 0.782~0.981, p =
      0.022), more prevalent of heart diseases (OR 6.082, 95% CI 1.963~18.839, p =
      0.002), and less cluster of family history of liver diseases (OR 0.291, 95% CI
      0.113~0.750, p = 0.011) when comparing with already known HCV infected residents.
      Among the 126 already know HCV infected residents, only 59 (46.8%) received
      antiviral treatment or regular follow-up. No concept or no willing to receive
      medical care was observed in 44 (34.9%) residents. CONCLUSION: In HCV endemic
      villages of Taiwan, residents with unaware HCV infection comprised about one
      third of HCV infected residents and exhibited obscure characteristics to
      identify. Less than half of already known HCV infected residents received
      adequate medical care. To eliminate HCV infection, vigorous efforts on enhancing
      screening coverage, educating update knowledge of liver diseases, and linking to
      medical care are urgently needed.

PMID- 29470548
TI  - Using aided cortical assessment as an objective tool to evaluate cochlear implant
      fitting in users with single-sided deafness.
AB  - OBJECTIVES: To assess the use of cortical auditory evoked potentials (CAEPs) to
      verify, and if necessary, optimize the cochlear implant (CI) fitting of adult CI
      users with postlingual single-sided deafness (SSD). METHODS: Sound field cortical
      responses to the speech tokens /m/, /g/, /t/, and /s/ were recorded from input to
      the CI while the normal hearing ear was masked. Responses were evaluated by
      visual inspection and classified as presence or absence of the CAEPs components
      P1, N1, P2. In case of an absence fitting was adjusted accordingly. After
      fitting, subjects were asked to use their new setting for 2-3 weeks for
      acclimatization purposes and then return for retesting. At retesting, new CAEP
      recordings were performed to objectively ensure that the new fitting maps
      effectively activated the auditory cortex. RESULTS: In 14/19 subjects, as per
      visual inspection, clear CAEPs were recorded by each speech token and were,
      therefore, not refit. In the other 5 subjects, CAEPs could not be evoked for at
      least one speech token. The fitting maps in these subjects were adjusted until
      clear CAEPs were evoked for all 4 speech tokens. CONCLUSIONS: CAEP can be used to
      quickly and objectively verify the suitability of CI fitting in experienced adult
      CI users with SSD. If used in the early post-implantation stage, this method
      could help CI users derive greater benefit for CI use and, therefore, be more
      committed to auditory training.

PMID- 29470549
TI  - Genome-wide identification and analysis of A-to-I RNA editing events in bovine by
      transcriptome sequencing.
AB  - RNA editing increases the diversity of the transcriptome and proteome. Adenosine
      to-inosine (A-to-I) editing is the predominant type of RNA editing in mammals and
      it is catalyzed by the adenosine deaminases acting on RNA (ADARs) family. Here,
      we used a largescale computational analysis of transcriptomic data from brain,
      heart, colon, lung, spleen, kidney, testes, skeletal muscle and liver, from three
      adult animals in order to identify RNA editing sites in bovine. We developed a
      computational pipeline and used a rigorous strategy to identify novel editing
      sites from RNA-Seq data in the absence of corresponding DNA sequence information.
      Our methods take into account sequencing errors, mapping bias, as well as
      biological replication to reduce the probability of obtaining a false-positive
      result. We conducted a detailed characterization of sequence and structural
      features related to novel candidate sites and found 1,600 novel canonical A-to-I
      editing sites in the nine bovine tissues analyzed. Results show that these sites
      1) occur frequently in clusters and short interspersed nuclear elements (SINE)
      repeats, 2) have a preference for guanines depletion/enrichment in the flanking
      5'/3' nucleotide, 3) occur less often in coding sequences than other regions of
      the genome, and 4) have low evolutionary conservation. Further, we found that a
      positive correlation exists between expression of ADAR family members and tissue
      specific RNA editing. Most of the genes with predicted A-to-I editing in each
      tissue were significantly enriched in biological terms relevant to the function
      of the corresponding tissue. Lastly, the results highlight the importance of the
      RNA editome in nervous system regulation. The present study extends the list of
      RNA editing sites in bovine and provides pipelines that may be used to
      investigate the editome in other organisms.

PMID- 29470550
TI  - The pregnane X receptor (PXR) and the nuclear receptor corepressor 2 (NCoR2)
      modulate cell growth in head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer
      worldwide. The pregnane X receptor (PXR) is a nuclear receptor regulating several
      target genes associated with cancer malignancy. We here demonstrated a
      significant effect of PXR on HNSCC cell growth, as evidenced in PXR knock-down
      experiments. PXR transcriptional activity is more importantly regulated by the
      presence of coactivators and corepressors than by PXR protein expression. To
      date, there is scarce information on the regulation of PXR in HNSCC and on its
      role in the pathogenesis of this disease. Coactivator and corepressor expression
      was screened through qRT-PCR in 8 HNSCC cell lines and correlated to PXR
      activity, determined by using a reporter gene assay. All cell lines considerably
      expressed all the cofactors assessed. PXR activity negatively correlated with
      nuclear receptor corepressor 2 (NCoR2) expression, indicating a major role of
      this corepressor in PXR modulation and suggesting its potential as a surrogate
      for PXR activity in HNSCC. To test the association of NCoR2 with the malignant
      phenotype, a subset of three cell lines was transfected with an over-expression
      plasmid for this corepressor. Subsequently, cell growth and chemoresistance
      assays were performed. To elucidate the mechanisms underlying NCoR2 effects on
      cell growth, caspase 3/7 activity and protein levels of cleaved caspase 3 and
      PARP were evaluated. In HNO97 cells, NCoR2 over-expression decreased cell growth,
      chemoresistance and increased cleaved caspase 3 levels, caspase activity and
      cleaved PARP levels. On the contrary, in HNO124 and HNO210 cells, NCoR2 over
      expression increased cell growth, drug resistance and decreased cleaved caspase 3
      levels, caspase activity and cleaved PARP levels. In conclusion, we demonstrated
      a role of PXR and NCoR2 in the modulation of cell growth in HNSCC. This may
      contribute to a better understanding of the highly variable HNSCC therapeutic
      response.

PMID- 29470551
TI  - Tph2-/- female mice restore socio-sexual recognition through upregulating ERalpha
      and OTR genes in the amygdala.
AB  - The central 5-hydroxytryptamine system impairs sociosexual behaviors and
      olfaction preferences in sexually naive mice. However, it remains unknown whether
      reproductive experiences impart an effect on the sexual olfactory preferences of
      female mice lacking central serotonin. Here, we aimed at examining such effects
      and the underlying mechanisms using Tph2 knockout female mice. Sexually naive
      Tph2-/- female mice failed to recognize olfactory cues regarding sex, genetic
      relatedness, and social hierarchy despite exhibiting normal olfactory
      discrimination. However, reproduction-experienced Tph2-/- female mice recovered
      sexual olfactory preferences, as did sexually naive Tph2+/+ females. Meanwhile,
      both the estrogen receptor alpha and oxytocin receptor in the amygdala of
      reproduction-experienced Tph2-/- females presented upregulated expression at the
      mRNA level and an upward tendency at the protein level vs. sexually naive Tph2-/-
      females. Intracerebroventricular administration of a combination of estrogen
      receptor alpha and oxytocin receptor agonists, but not either agent alone, could
      restore the sexual olfactory preferences of sexually naive Tph2-/- female mice to
      some degree. We speculate that estrogen receptor alpha and oxytocin receptor
      activation in the amygdala after reproductive experiences restores sexual
      olfactory recognition in Tph2-/- female mice.

PMID- 29470553
TI  - Pneumocystis and interactions with host immune receptors.

PMID- 29470552
TI  - Increased HIV-1 transcriptional activity and infectious burden in peripheral
      blood and gut-associated CD4+ T cells expressing CD30.
AB  - HIV-1-infected cells persist indefinitely despite the use of combination
      antiretroviral therapy (ART), and novel therapeutic strategies to target and
      purge residual infected cells in individuals on ART are urgently needed. Here, we
      demonstrate that CD4+ T cell-associated HIV-1 RNA is often highly enriched in
      cells expressing CD30, and that cells expressing this marker considerably
      contribute to the total pool of transcriptionally active CD4+ lymphocytes in
      individuals on suppressive ART. Using in situ RNA hybridization studies, we show
      co-localization of CD30 with HIV-1 transcriptional activity in gut-associated
      lymphoid tissues. We also demonstrate that ex vivo treatment with brentuximab
      vedotin, an antibody-drug conjugate (ADC) that targets CD30, significantly
      reduces the total amount of HIV-1 DNA in peripheral blood mononuclear cells
      obtained from infected, ART-suppressed individuals. Finally, we observed that an
      HIV-1-infected individual, who received repeated brentuximab vedotin infusions
      for lymphoma, had no detectable virus in peripheral blood mononuclear cells.
      Overall, CD30 may be a marker of residual, transcriptionally active HIV-1
      infected cells in the setting of suppressive ART. Given that CD30 is only
      expressed on a small number of total mononuclear cells, it is a potential
      therapeutic target of persistent HIV-1 infection.

PMID- 29470554
TI  - Likelihood ratios of quantitative laboratory results in medical diagnosis: The
      application of Bezier curves in ROC analysis.
AB  - Receiver operating characteristic (ROC) analysis is widely used to describe the
      discriminatory power of a diagnostic test to differentiate between populations
      having or not having a specific disease, using a dichotomous threshold. In this
      way, positive and negative likelihood ratios (LR+ and LR-) can be calculated to
      be used in Bayes' way of estimating disease probabilities. Similarly, LRs can be
      calculated for certain ranges of test results. However, since many diagnostic
      tests are of quantitative nature, it would be desirable to estimate LRs for each
      quantitative result. These LRs are equal to the slope of the tangent to the ROC
      curve at the corresponding point. Since the exact distribution of test results in
      diseased and non-diseased people is often not known, the calculation of such LRs
      for quantitative test results is not straightforward. Here, a simple distribution
      independent method is described to reach this goal using Bezier curves that are
      defined by tangents to a curve. The use of such a method would help in
      standardizing quantitative test results, which are not always comparable between
      different test providers, by reporting them as LRs for a specific diagnosis, in
      addition to, or instead of, quantities such as mg/L or nmol/L, or even indices or
      units.

PMID- 29470555
TI  - Bernese motive and goal inventory in exercise and sport: Validation of an updated
      version of the questionnaire.
AB  - Target group-specific intervention strategies are often called for in order to
      effectively promote exercise and sport. Currently, motives and goals are rarely
      included systematically in the design of interventions, despite the key role they
      play in well-being and adherence to exercise. The Bernese motive and goal
      inventory (BMZI) allows an individual diagnosis of motives and goals in exercise
      and sport in people in middle adulthood. The purpose of the present study was to
      elaborate on the original BMZI and to modify the questionnaire in order to
      improve its psychometric properties. The study is based on data from two samples
      (sample A: 448 employees of companies and authorities; sample B: 853 patients of
      a medical rehabilitation programme). We applied confirmatory factor analysis and
      exploratory structural equation modelling. Overall, both the original and the
      updated BMZI had an acceptable to good validity and a good reliability. However,
      the revised questionnaire had slightly better reliability. The updated BMZI
      consists of 23 items and covers the following motives and goals: Body/Appearance,
      Contact, Competition/Performance, Aesthetics, Distraction/Catharsis, Fitness and
      Health. It is recommended as an economical inventory for the individual diagnosis
      of important psychological conditions for exercise and sport.

PMID- 29470557
TI  - Design of a 3D-printed, open-source wrist-driven orthosis for individuals with
      spinal cord injury.
AB  - Assistive technology, such as wrist-driven orthoses (WDOs), can be used by
      individuals with spinal cord injury to improve hand function. A lack of
      innovation and challenges in obtaining WDOs have limited their use. These
      orthoses can be heavy and uncomfortable for users and also time-consuming for
      orthotists to fabricate. The goal of this research was to design a WDO with user
      (N = 3) and orthotist (N = 6) feedback to improve the accessibility,
      customizability, and function of WDOs by harnessing advancements in 3D-printing.
      The 3D-printed WDO reduced hands-on assembly time to approximately 1.5 hours and
      the material costs to $15 compared to current fabrication methods. Varying
      improvements in users' hand function were observed during functional tests, such
      as the Jebsen Taylor Hand Function Test. For example, one participant's ability
      on the small object task improved by 29 seconds with the WDO, while another
      participant took 25 seconds longer to complete this task with the WDO. Two users
      had a significant increase in grasp strength with the WDO (13-122% increase),
      while the other participant was able to perform a pinching grasp for the first
      time. The WDO designs are available open-source to increase accessibility and
      encourage future innovation.

PMID- 29470556
TI  - No evidence for association between APOL1 kidney disease risk alleles and Human
      African Trypanosomiasis in two Ugandan populations.
AB  - BACKGROUND: Human African trypanosomiasis (HAT) manifests as an acute form caused
      by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma
      brucei gambiense (Tbg). Previous studies have suggested a host genetic role in
      infection outcomes, particularly for APOL1. We have undertaken candidate gene
      association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to
      determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG,
      MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT.
      METHODOLOGY AND RESULTS: We included 238 and 202 participants from the Busoga Tbr
      and Northwest Uganda Tbg endemic areas respectively. Single Nucleotide
      Polymorphism (SNP) genotype data were analysed in the CGAS. The study was powered
      to find odds ratios > 2 but association testing of the SNPs with HAT yielded no
      positive associations i.e. none significant after correction for multiple
      testing. However there was strong evidence for no association with Tbr HAT and
      APOL1 G2 of the size previously reported in the Kabermaido district of Uganda.
      CONCLUSIONS/SIGNIFICANCE: A recent study in the Soroti and Kaberamaido focus in
      Central Uganda found that the APOL1 G2 allele was strongly associated with
      protection against Tbr HAT (odds ratio = 0.2, 95% CI: 0.07 to 0.48, p = 0.0001).
      However, in our study no effect of G2 on Tbr HAT was found, despite being well
      powered to find a similar sized effect (OR = 0.9281, 95% CI: 0.482 to 1.788, p =
      0.8035). It is possible that the G2 allele is protective from Tbr in the
      Soroti/Kabermaido focus but not in the Iganga district of Busoga, which differ in
      ethnicity and infection history. Mechanisms underlying HAT infection outcome and
      virulence are complex and might differ between populations, and likely involve
      several host, parasite or even environmental factors.

PMID- 29470558
TI  - HIC1 links retinoic acid signalling to group 3 innate lymphoid cell-dependent
      regulation of intestinal immunity and homeostasis.
AB  - The intestinal immune system must be able to respond to a wide variety of
      infectious organisms while maintaining tolerance to non-pathogenic microbes and
      food antigens. The Vitamin A metabolite all-trans-retinoic acid (atRA) has been
      implicated in the regulation of this balance, partially by regulating innate
      lymphoid cell (ILC) responses in the intestine. However, the molecular mechanisms
      of atRA-dependent intestinal immunity and homeostasis remain elusive. Here we
      define a role for the transcriptional repressor Hypermethylated in cancer 1
      (HIC1, ZBTB29) in the regulation of ILC responses in the intestine. Intestinal
      ILCs express HIC1 in a vitamin A-dependent manner. In the absence of HIC1, group
      3 ILCs (ILC3s) that produce IL-22 are lost, resulting in increased susceptibility
      to infection with the bacterial pathogen Citrobacter rodentium. Thus, atRA
      dependent expression of HIC1 in ILC3s regulates intestinal homeostasis and
      protective immunity.

PMID- 29470559
TI  - Changes in the prevalence and social distribution of cardiovascular disease and
      risk factors in India.

PMID- 29470560
TI  - Renal artery revascularisation: can we predict who benefits?

PMID- 29470561
TI  - Safety and Efficacy of Cosmetic Augmentation of the Nasal Tip and Nasal Dorsum
      With Expanded Polytetrafluoroethylene: A Randomized Clinical Trial.
AB  - Importance: Expanded polytetrafluoroethylene (ePTFE) is a widely used alloplast,
      but studies of augmentation of the nasal tip and nasal dorsum with ePTFE are
      lacking. Objective: To investigate whether attaching the conchal cartilage as
      shield grafts at the distal end of the graft can prevent extrusion and whether
      the use of ePTFE in the nasal tip can achieve a stable aesthetic outcome. Design,
      Setting, and Participants: A randomized clinical trial was performed from April
      1, 2006, to October 31, 2008. Follow-up was completed in 2012 and 2017. The study
      was conducted at the Department of Plastic and Reconstructive Surgery, Shanghai
      Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine,
      Shanghai, China. One hundred fifty patients seeking rhinoplasty were recruited,
      and 129 were eligible for inclusion in the study. All the recruited patients were
      intent-to-treat populations who were randomized into 2 groups: an ePTFE-only
      group and an ePTFE with conchal cartilage group. Interventions: Expanded PTFE was
      used for augmentation of the nasal tip and nasal dorsum in both groups. Conchal
      cartilage was placed above the distal end in the ePTFE with conchal cartilage
      group. Main Outcomes and Measures: Preoperative and postoperative standard
      photographs were obtained. Postoperative satisfaction and complications were
      evaluated. Results: Of the 129 patients (mean age [range], 28 years [21-45
      years]; 6 male and 123 female) eligible for inclusion in this study, 76 (mean age
      [range], 31 years [22-45 years]; 4 male and 72 female) were available for follow
      up (mean [range], 106.9 months [100-131 months]) through 2017, including 39 in
      the ePTFE-only group and 37 in the ePTFE with conchal cartilage group. Infection
      occurred in 2 patients (5%) in the ePTFE-only group vs 1 patient (3%) in the
      ePTFE with conchal cartilage group (infection rate [OR, 1.946; 95% CI, 0.169
      22.413; P > .99]). Soft-tissue reaction occurred in 0 patients in the ePTFE-only
      group vs 1 patient (3%) in the ePTFE with conchal cartilage group (soft-tissue
      reaction rate [OR, 0.000; 95% CI, 0.000-8.538; P = .49]). Irregularity occurred
      in 0 patients in the ePTFE-only group vs 3 patients (8%) in the ePTFE with
      conchal cartilage group (irregularity rate [OR, 0.000; 95% CI, 0.000-1.066; P =
      .11]). Extrusion occurred in neither of the 2 groups. Conclusions and Relevance:
      A new technique using ePTFE alone for augmentation of the nasal tip and nasal
      dorsum achieved safe, attractive, and acceptable outcomes in nasal contouring and
      patient satisfaction. The use of conchal cartilage as a shield in the nasal tip
      is not necessary. Level of Evidence: 1. Trial Registration: Chinese Clinical
      Trial Registry identifier: ChiCTR-INR-17011101.

PMID- 29470562
TI  - Association of Nasal Tip Rotation Outcome Estimation With the New Domes Technique
      in Primary Rhinoplasty.
AB  - Importance: The postoperative changes in the rotation of the nasal tip in
      rhinoplasty must be estimated for the surgical planning. Objective: To determine
      whether the outcome in the rotation angle of the nasal tip can be estimated in
      patients undergoing primary rhinoplasty with the new domes technique. Design,
      Setting, and Participants: This retrospective analytic cohort study included 323
      patients undergoing primary rhinoplasty with the new domes technique in a private
      clinic in Bogota, Colombia, by a single surgeon from January 1, 2011, through
      January 31, 2016. Patients undergoing secondary rhinoplasty and those with less
      than 6 months of follow-up were excluded. Exposures: Primary rhinoplasty using
      the new domes technique. Main Outcomes and Measures: Measurement of the rotation
      angle of the nasal tip before and 1 week and 6 months after surgery. The main
      variable taken into consideration was the measurement, in millimeters, of the
      lateralized nasal domes. Results: A total of 323 patients (288 women [89.2%] and
      35 men [10.8%]; mean age, 27.8 years; age range, 13-70 years) were included in
      the study. The mean (SD) preoperative nasolabial angle was 92.7 degrees  (4.4
      degrees ; range, 77 degrees -107 degrees ); at 1 postoperative week, 105.5
      degrees  (4.9 degrees ; range, 92 degrees -120 degrees ); and at 6 postoperative
      months, 102.1 degrees  (4.6 degrees ; range, 90 degrees -115 degrees ). The mean
      (SD) increase of the rotation that was achieved per lateralized millimeter was
      3.6 degrees  (2.0 degrees ). The mean (SD) rotation angle at 6 months decreased
      to 3.4 degrees  (2.4 degrees ). Conclusions and Relevance: The new domes
      technique was reliable and reproducible in most patients. Despite the
      unpredictable inflammatory changes, the exact lateralization in millimeters with
      the new domes technique allowed precise estimation of the long-term outcome of
      the rotation of the nasal tip, enabling the surgeon to determine from the
      preoperative plan the definitive rotation angle of the nose. Level of Evidence:
      4.

PMID- 29470564
TI  - A Painful Submandibular Mass in a Patient With Bruxism.

PMID- 29470563
TI  - Nonsurgical Treatment for Posttraumatic Complete Facial Nerve Paralysis.
AB  - Importance: Current recommendations envisage early surgical exploration for
      complete facial nerve paralysis associated with temporal bone fracture and
      unfavorable electrophysiologic features (response to electroneuronography, <5%).
      However, the evidence base for such a practice is weak, with the potential for
      spontaneous improvement being unknown, and the expected results from alternative
      nonsurgical treatment also undefined. Objective: To document the results of
      nonsurgical treatment for posttraumatic complete facial paralysis with
      undisplaced temporal bone fracture and unfavorable electrophysiologic features.
      Design, Setting, and Participants: Prospective cohort study recruiting from April
      2010 to April 2013 at a tertiary care university hospital. Follow-up continued
      until 9 months or until complete recovery if earlier. Study group included 28
      patients with head injury-associated complete unilateral facial nerve paralysis
      with unfavorable results of electroneuronography (<5% response) with or without
      undisplaced temporal bone fracture. Undisplaced temporal bone fractures were
      documented in 26 patients (24 longitudinal fractures and 2 transverse fractures).
      Interventions: Patients received prednisolone, 1 mg/kg, for 3 weeks combined with
      clinical monitoring every 2 weeks and electromyography monitoring every 4 weeks.
      As per study protocol, surgical exploration was limited to patients demonstrating
      motor end plate degeneration on results of electromyography, or having no
      improvement until 18 weeks. Main Outcomes and Measures: Facial nerve function was
      evaluated by the House-Brackmann grading system; Forehead, Eye, Mouth, and
      Associated defect grading system; and the modified Adour system. Observations
      were completed at 40 weeks. Results: Among the 28 patients in the study (3 women
      and 25 men; mean [SD] age, 32.2 [8.7] years), facial nerve recovery with
      conservative treatment alone was noted in all patients. No recovery was seen in
      any patient at the initial 4-week review. The first signs of clinical recovery
      were noted in 4 patients by 8 weeks, in 27 patients by 12 weeks, and in all
      patients by 20 weeks. No patient required surgical exploration. At 40 weeks, 27
      patients recovered to House-Brackmann grade I/II and 1 patient to grade III. All
      24 patients with longitudinal fractures had grade I/II recovery. Conclusions and
      Relevance: For undisplaced temporal bone fractures, nonsurgical treatment leads
      to near-universal recovery to House-Brackmann grade I/II and is superior to
      reported surgical results. Recovery is delayed and usually first manifests at 8
      to 12 weeks after the fracture. In the current era of high-resolution computed
      tomography, surgical exploration should not be first-line treatment for
      undisplaced longitudingal temporal bone fractures associated with complete facial
      nerve paralysis and unfavorable electrophysiologic features.

PMID- 29470565
TI  - Sociodemographic, Medical, and Psychosocial Factors Associated With Supportive
      Care Needs in Adults Diagnosed With Uveal Melanoma.
AB  - Importance: Understanding supportive care needs in patients with cancer is
      important for developing approaches that enhance quality of life and promote
      satisfaction with care. Objective: To characterize the nature and frequency of
      sociodemographic, medical, and psychosocial factors associated with unmet needs
      in patients with uveal melanoma 1 week and 3 months after diagnosis. Design,
      Setting, and Participants: This 3-month, prospective, longitudinal survey study
      was conducted at a university-based ophthalmology practice from June 1, 2007, to
      July 1, 2011. Data were analyzed in April 2017. Consecutive patients (n = 429)
      scheduled for diagnostic evaluation for an intraocular abnormality were assessed
      for eligibility. Participants were ineligible (n = 25) if they were younger than
      18 years, had previous advanced cancer, or evidenced cognitive impairment. Of the
      patients who provided informed consent (n = 306), those subsequently diagnosed
      with uveal melanoma by an ophthalmologist (n = 107) were included in the
      analysis. Main Outcomes and Measures: Unmet needs (ie, desire for help in
      psychological, physical, health information, communication, or social domains)
      were assessed using the Cancer Needs Questionnaire. Multivariable regression
      analyses determined factors associated with unmet need severity across 3 months.
      Results: One hundred seven patients (58 [54%] men; mean [SD] age, 59.0 [12.8]
      years) completed the baseline assessment. At 1 week after diagnosis, nearly all
      patients (85 of 86 [99%]) expressed at least 1 unmet need, as did 68 of 79 (86%)
      3 months later. The most frequently endorsed needs were in the health information
      and psychological domains. Patients' unmet needs declined significantly over 3
      months (mean [SD] change, -10.0 [14.4]; 95% CI, -6.4 to -13.6; t = -5.6).
      Sociodemographic and medical characteristics were unrelated to unmet need
      severity. However, higher prediagnosis instrumental social support (b = -0.2; 95%
      CI, -0.3 to -0.1; z = -2.8) and lower neuroticism (b = 0.3; 95% CI, 0.1-0.5; z =
      2.9) predicted lower unmet need severity 1 week after diagnosis. Having a smaller
      social network predicted lower unmet need severity 3 months after diagnosis (b <
      0.1; 95% CI, <0.1 to <0.1; z = 2.4) as well as a decline in needs from diagnosis
      to 3 months later (b < 0.1; 95% CI, <0.1 to <0.1; z = 2.3). Conclusions and
      Relevance: Within 1 week after diagnosis and 3 months later, most patients with
      uveal melanoma cited important health information and psychological needs. These
      findings suggest that prior to or at diagnosis, the severity of such needs and
      psychosocial factors that may be associated can be identified for proactive
      supportive intervention.

PMID- 29470566
TI  - Comparison of Subjective Assessment and Precise Quantitative Assessment of Lesion
      Distribution in Diabetic Retinopathy.
AB  - Importance: Predominantly peripheral disease in eyes with nonproliferative
      diabetic retinopathy (DR) is suggested as a potential strong risk factor for
      progression to proliferative disease. However, the reliability and optimal method
      for the assessment of lesion distribution are still uncertain. Objective: To
      compare agreement between subjective assessment and precise quantification of
      lesion burden in ultrawidefield (UWF) images of eyes with DR. Design, Setting,
      and Participants: This multisite cross-sectional study examines UWF pseudocolor
      images acquired from DR screening clinic patients from December 20, 2014, through
      August 1, 2014. Of 104 cases, 161 eyes with DR were included. Data analysis was
      conducted from June 1, 2016, through December 1, 2016 at the Doheny Image Reading
      Center. Main Outcomes and Measures: Distribution of DR lesions in eyes was
      assessed subjectively and quantitatively, and eyes were classified as having
      predominantly central lesions (PCLs) or predominantly peripheral lesions (PPLs).
      The frequency and surface area (SA) of each lesion type were quantified.
      Intergrader and subjective vs quantitative classification were compared for level
      of agreement. Several methods of determining PPL distribution were also compared.
      Results: On subjective frequency-based evaluation by graders, 133 eyes were
      classified as having PCL, and 28 eyes as having PPL. On exact quantification of
      lesion SA, 121 eyes were classified as PCL, and 40 eyes as having PPL. On SA
      based quantification, 134 eyes were classified as having PCL, and 27 eyes as
      having PPL. There was a significant difference between qualitative and
      quantitative classification of DR lesion distribution for both frequency-based
      (mean difference [SD]: PCL, 6 [2]; PPL, 13 [6]; P < .001) and SA-based (mean
      difference [SD]: PCL, 6 [1]; PPL, 20 [7]; P < .001) methods. Both intergrader
      reproducibility and subjective vs quantitative agreement were higher with
      frequency-based classification. Conclusions and Relevance: Subjective assessment
      of PPL DR lesions on UWF images differed in some cases from precise quantitative
      assessments, particularly when considering the area of lesions. These findings
      highlight the benefit of objective quantitative approaches to DR assessment,
      which may facilitate the development of a more precise DR scoring system.

PMID- 29470567
TI  - Reappraising the Psychosocial Needs of Patients With Uveal Melanoma.

PMID- 29470568
TI  - Reducing Overtreatment of Cancer With Precision Medicine: Just What the Doctor
      Ordered.

PMID- 29470569
TI  - Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed
      Tomography in Locally Advanced, Recurrent, and Metastatic Prostate Cancer.

PMID- 29470570
TI  - A Magnetic Resonance Imaging-Based Prediction Model for Prostate Biopsy Risk
      Stratification.
AB  - Importance: Multiparametric magnetic resonance imaging (MRI) in conjunction with
      MRI-transrectal ultrasound (TRUS) fusion-guided biopsies have improved the
      detection of prostate cancer. It is unclear whether MRI itself adds additional
      value to multivariable prediction models based on clinical parameters. Objective:
      To determine whether an MRI-based prediction model can reduce unnecessary
      biopsies in patients with suspected prostate cancer. Design, Setting, and
      Participants: Patients underwent MRI, MRI-TRUS fusion-guided biopsy, and 12-core
      systematic biopsy in 1 session. The development cohort used to derive the
      prediction model consisted of 400 patients from 1 institution enrolled between
      May 14, 2015, and August 31, 2016, and the validation cohort included 251
      patients from 2 independent institutions who underwent biopsies between April 1,
      2013, and June 30, 2016, at 1 institution and between July 1, 2015, and October
      31, 2016, at the other institution. The MRI model included MRI-derived parameters
      in addition to clinical variables. Area under the curve of receiver operating
      characteristic curves and decision curve analysis were performed. Main Outcomes
      and Measures: Risk of clinically significant prostate cancer on biopsy, defined
      as a Gleason score of 3 + 4 or higher in at least 1 biopsy core. Results:
      Overall, 193 (48.3%) of the 400 patients in the development cohort (mean [SD] age
      at biopsy, 64.3 [7.1] years) and 96 (38.2%) of the 251 patients in the validation
      cohort (mean [SD] age at biopsy, 64.9 [7.2] years) had clinically significant
      prostate cancer, defined as a Gleason score greater than or equal to 3 + 4. By
      applying the model to the external validation cohort, the area under the curve
      increased from 64% to 84% compared with the baseline model (P < .001). At a risk
      threshold of 20%, the MRI model had a lower false-positive rate than the baseline
      model (46% [95% CI, 32%-66%] vs 92% [95% CI, 70%-100%]), with only a small
      reduction in the true-positive rate (89% [95% CI, 85%-96%] vs 99% [95% CI, 89%
      100%]). Eighteen of 100 fewer biopsies could have been performed, with no
      increase in the number of patients with missed clinically significant prostate
      cancers. Conclusions and Relevance: The inclusion of MRI-derived parameters in a
      risk model could reduce the number of unnecessary biopsies while maintaining a
      high rate of diagnosis of clinically significant prostate cancers.

PMID- 29470572
TI  - Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed
      Tomography in Locally Advanced, Recurrent, and Metastatic Prostate Cancer-Reply.

PMID- 29470571
TI  - Prevalence of Myelin Oligodendrocyte Glycoprotein and Aquaporin-4-IgG in Patients
      in the Optic Neuritis Treatment Trial.
AB  - Importance: Autoantibodies to aquaporin-4 (AQP4) and myelin oligodendrocyte
      glycoprotein (MOG) are recently established biomarkers of autoimmune optic
      neuritis whose frequency and accompanying phenotype, especially for MOG-IgG, are
      still being characterized. The Optic Neuritis Treatment Trial (ONTT) was a well
      known randomized clinical trial in optic neuritis; therefore, knowledge of the
      serostatus and accompanying phenotype of these patients would be useful to
      determine the frequency of these antibodies in patients presenting with typical
      monocular optic neuritis and their outcomes. Objectives: To determine the AQP4
      IgG and MOG-IgG serostatus of patients within the ONTT and describe the clinical
      features of seropositive patients. Design, Setting, and Participants: In this
      follow-up study of the randomized clinical trial, ONTT, conducted between July 1,
      1988, and June 30, 1991, analysis of serum for AQP4-IgG and MOG-IgG was performed
      from January 1 to April 30, 2017. A total of 177 patients from the ONTT with
      acute optic neuritis and serum available for analysis were enrolled from 13
      academic referral centers. Interventions: Analysis of serum for AQP4-IgG and MOG
      IgG was performed at Mayo Clinic Neuroimmunology Laboratory in 2017 with a flow
      cytometry, live cell, AQP4- and MOG-transfected cell-based assay. Main Outcomes
      and Measures: Aquaporin-4-IgG and MOG-IgG serostatus. Results: Of the 177
      patients in the study (135 women and 42 men; mean [SD] age, 32.8 [6.9] years), 3
      were positive for MOG-IgG (1.7%) and none were positive for AQP4-IgG. All 3
      patients positive for MOG-IgG had disc edema at presentation. Two patients later
      had a single episode of recurrent optic neuritis. All 3 patients had complete
      recovery of visual acuity, and none were corticosteroid dependent, although
      peripheral visual field loss persisted in 1 patient. None of the 3 patients
      positive for MOG-IgG had demyelinating lesions on magnetic resonance imaging
      scans, and none had developed multiple sclerosis at the 15-year follow-up.
      Conclusions and Relevance: Frequency of MOG-IgG was rare in the ONTT, and AQP4
      IgG was not found in patients in the ONTT. Characteristics of patients positive
      for MOG-IgG in the ONTT support the previously described phenotype of MOG-IgG
      optic neuritis. Myelin oligodendrocyte glycoprotein-related disease appears to be
      a different entity than multiple sclerosis. Overall, AQP4-IgG and MOG-IgG may be
      less common in isolated optic neuritis than previously reported.

PMID- 29470573
TI  - Factors Associated With Health-Related Quality of Life in Medically and
      Surgically Treated Patients With Glaucoma.
AB  - Importance: Health-related quality of life (HRQOL) is often reduced with
      glaucoma, but associated factors are poorly understood. Objective: To determine
      factors associated with reduced HRQOL in medically and surgically treated
      patients with glaucoma. Design, Setting, and Participants: Prospective cohort
      study at a tertiary referral glaucoma practice, with 160 consecutive,
      prospectively enrolled medically or surgically treated adult patients with
      glaucoma. Main Outcome and Measures: All patients completed 2 HRQOL
      questionnaires (the 25-item National Eye Institute Visual Function Questionnaire
      and the Adult Strabismus-20 questionnaire [AS-20]). Thirty-six patients had
      undergone glaucoma drainage device surgery, 51 underwent trabeculectomy, and 73
      were medically treated. Factors considered for association with HRQOL in multiple
      regression analyses were age, sex, best-eye and worst-eye mean deviation on
      Humphrey visual fields, treatment modality, best-eye and worst-eye visual acuity,
      and diplopia. Results: The mean (SD) age of participants was 69 (13) years, 63%
      were female, 97% were white, 93% were not Hispanic, and the mean deviation (SD)
      was -13 (10) dB. Reduced HRQOL was associated with worse diplopia (Diplopia
      Questionnaire score) on 6 subscales (range of partial r2 [rp2], 0.207-0.069).
      Reduced HRQOL was associated with lower best-eye mean deviation on 5 of 6
      subscales (rp2 range, 0.379-0.027), lower worst-eye mean deviation on 4 of 6 (rp2
      range, 0.242-0.046), treatment group on 3 of 6 (rp2 range, 0.190-0.025), lower
      worst-eye visual acuity on 5 of 6 (rp2 range, 0.063-0.025), lower best-eye visual
      acuity on 2 of 6 (rp2 range, 0.032-0.017), and younger age on 2 of 6 (rp2 range,
      0.021-0.014). In adjusted analyses, glaucoma drainage device was associated with
      worse HRQOL in 3 AS-20 subscales compared with trabeculectomy and 2 AS-20
      subscales compared with medical. Differences ranged from -14.7 to -7.4, with half
      the absolute magnitude of the full range of the 95% CI ranging from 9.2 to 5.7.
      Conclusions and Relevance: Our findings support the assertion that reduced HRQOL
      is common in surgically and medically treated patients with glaucoma. Overall,
      poor HRQOL in patients with glaucoma is moderately associated with worse
      diplopia, lower mean deviation on visual field testing in either eye, poorer
      visual acuity in either eye, treatment type, and younger age. Previous glaucoma
      drainage device surgery was specifically associated with poorer HRQOL compared
      with trabeculectomy or medical treatment. Psychosocial effects of glaucoma
      drainage device should be considered when counseling patients with glaucoma.

PMID- 29470574
TI  - Changes in Scope of Procedures Performed by Pediatric Otolaryngologists in the
      Past Decade.
AB  - Importance: Monitoring current trends in pediatric otolaryngology will help
      adjust our training and practice paradigms in a way that ensures the long-term
      viability of the specialty. Objectives: To gauge the current scope of pediatric
      otolaryngology (ORL) practice within and outside of the United States and to
      identify changes in caseload over the past decade. Design, Setting, and
      Participants: An online survey was sent to pediatric ORL chairs and/or fellowship
      directors at 42 institutions in the United States and abroad. For 59 procedures,
      respondents were asked to estimate the percentage of cases performed by their
      department, determine whether this percentage has changed over the past 10 years
      (2006-2016), and identify any other specialties performing the procedure. Data
      were collected during a 2-week period in October 2016, from October 7 through 21,
      and analyzed from November 2016 through February 2017. Main Outcomes and
      Measures: Main outcomes included the percentage of operations currently performed
      by the respondent's department for each procedure; whether this percentage has
      decreased, increased, or remained the same over the past decade; other
      specialties that perform each procedure; and any procedures added to or
      eliminated from the respondent's practice over the past decade. Results:
      Respondents from 33 of the 42 academic institutions completed the survey (23 in
      the United States and 10 international; 79% response rate). Respondents reported
      the least involvement in procedures pertaining to facial plastic and
      reconstructive surgery, aerodigestive endoscopy, and congenital anomalies.
      Conversely, a mean (SD) of 91% (7%) reported performing 90% to 100% of otology,
      airway, rhinology, and general procedures. A mean (SD) of 82% (11%) reported that
      their department's involvement in each procedure has remained the same from 2006
      to 2016. Conclusions and Relevance: The specialty of pediatric ORL has evolved
      over the past decade. There has been a notable decline in involvement in facial
      plastic and reconstructive surgery and treatment of vascular malformations and
      esophageal disorders. The management of thyroid disease is in flux. Monitoring
      current trends to adjust training and practice paradigms will ensure the long
      term viability of the specialty.

PMID- 29470575
TI  - Discharge Destination and Disparities in Postoperative Care.

PMID- 29470576
TI  - Navigating Prostate Cancer Screening in the Real World of Primary Care: The
      Mirage and the Quicksand.

PMID- 29470577
TI  - Novel Ingested Foreign Bodies-A Fidget Spinner Case Report.

PMID- 29470578
TI  - Spending by Commercial Insurers on Chemotherapy Based on Site of Care, 2004-2014.

PMID- 29470580
TI  - Data Presentation Error in Results Paragraph of Abstract.

PMID- 29470579
TI  - Defining the Most Appropriate Primary End Point in Phase 2 Trials of Immune
      Checkpoint Inhibitors for Advanced Solid Cancers: A Systematic Review and Meta
      analysis.
AB  - Importance: Checkpoint inhibitors have a unique mechanism of action that differs
      from chemotherapy or targeted therapies. The validity of objective response rate
      (ORR) as a surrogate for progression-free survival (PFS) and overall survival
      (OS) in checkpoint-inhibitor trials is uncertain. Objective: To determine the
      types of primary end points used in phase 2 checkpoint-inhibitor trials, and to
      assess the strength of associations for ORR with PFS and OS. Data Sources: Trials
      listed in electronic databases from 2000 to 2017 (PREMEDLINE, MEDLINE, Embase,
      and the Cochrane Central Register of Controlled Trials). Study Selection:
      Advanced solid cancers in phase 2 and phase 3 trials. Data Extraction and
      Synthesis: Correlations between ORR odds ratios and hazard ratios (HRs) for PFS
      and OS were examined for randomized comparisons. Within checkpoint-inhibitor
      treatment arms, correlations for ORR with 6-month PFS and 12-month OS rates were
      examined. All analyses were weighted by trial size. Multivariable models to
      predict 6-month PFS and 12-month OS rates from ORR were developed and their
      performance validated in an independent sample of trials. Main Outcomes and
      Measures: Correlation coefficient (r) of ORR with PFS and OS. Results: Of 87
      phase 2 trials identified, ORR was the most common (52 [60%]) primary end point.
      Twenty randomized clinical trials with 25 treatment comparisons were identified.
      Checkpoint-inhibitor therapy was associated with pooled ORR of 24% (95% CI, 18%
      31%). For randomized comparisons, r between ORR odds ratio and PFS HR was 0.63
      (95% CI, 0.35-0.89), ORR odds ratio and OS HR was 0.57 (95% CI, 0.23-0.89), and
      between PFS HR and OS HR was 0.42 (95% CI, 0.04-0.81). Within the checkpoint
      inhibitor arms, r correlation coefficients between ORR with 6-month PFS, ORR with
      12-month OS, and 6-month PFS with 12-month OS were 0.37 (95% CI, -0.06 to 0.95),
      0.08 (95% CI, -0.17 to 0.70), and 0.74 (95% CI, 0.57-0.92), respectively. In
      validation, when 6-month PFS was used to predict 12-month OS, there was a good
      calibration between actual and predicted 12-month OS. When ORR was used to
      predict 6-month PFS and 12-month OS rates, respectively, the actual vs predicted
      rates calibrated poorly. Conclusions and Relevance: In checkpoint-inhibitor
      trials, ORR correlated poorly with OS. For future phase 2 studies, 6-month PFS
      rate is recommended as an end point.

PMID- 29470581
TI  - Progressive Bilateral Scleral Pigmentation in a Patient With Ocular Hypertension.

PMID- 29470583
TI  - Virtual Reality Check: Are You Ready?

PMID- 29470582
TI  - Prognostic Factors for Complete Response to Ibrutinib in Patients With Chronic
      Lymphocytic Leukemia: A Pooled Analysis of 2 Clinical Trials.
AB  - Importance: Ibrutinib, a first-in-class Bruton tyrosine kinase inhibitor taken
      once daily, is approved in the United States for patients with chronic
      lymphocytic leukemia/small lymphocytic lymphoma and allows for treatment without
      chemotherapy. Extended treatment with ibrutinib has demonstrated increased
      complete response (CR) rates over time. Objective: To analyze baseline factors
      that predict CR in patients with chronic lymphocytic leukemia/small lymphocytic
      lymphoma treated with ibrutinib. Design, Setting, and Participants: Univariate
      and multivariate analyses of pooled data from 2 clinical trials were used to
      assess the prognostic value of baseline factors associated with CR in 327
      patients from the PCYC-1102 and PCYC-1112 studies treated with single-agent
      ibrutinib. Participants were followed up in academic and community medical
      centers in the United States, the United Kingdom, Australia, France, Italy,
      Ireland, Poland, Spain, and Austria. Main Outcomes and Measures: Odds ratio (OR)
      of CR rate. Results: The 327 patients included in this analysis had a median age
      of 67 years (range, 30-86 years) and 227 (69.4%) were male. At baseline, 185
      patients (56.6%) had bulky disease (lymph node >=5 cm), 184 (56.3%) had advanced
      stage disease, and 182 (55.7%) had an Eastern Cooperative Oncology Group
      performance status of 1 or higher. Thirty-one patients (9.5%) were in the first
      line setting; 38 (11.6%) had undergone 1 previous therapy, 81 (24.8%) had
      undergone 2, and 177 (54.1%) had undergone 3 or more; patients with
      relapsed/refractory disease had undergone a median of 3 (range, 0-12) previous
      therapies. Median time on study was 26.4 months (range, 0.3-55.6 months). Thirty
      two of the 327 patients (9.8%) treated with ibrutinib had a CR (PCYC-1102:
      relapsed/refractory, 12 of 101 [11.9%]; treatment-naive, 8 of 31 [25.8%]; and
      PCYC-1112: 12 of 195 [6.2%]). The median time to CR for these patients was 14.7
      months (range, 4.6-47.1 months). Univariate analysis of baseline factors showed
      that bulky disease, clinical stage, number of previous therapies, and beta2
      microglobulin concentration had a significant effect on the odds of CR. The final
      multivariate model showed that patients with no previous therapy vs patients with
      at least 1 previous therapy (OR, 2.65; 95% CI, 1.01-6.95; P = .047) and patients
      without bulky disease (lymph node <5 cm) vs those with bulky disease (lymph node
      >=5 cm [OR, 4.97; 95% CI, 1.91-12.91; P = .001]) had an increased likelihood of
      CR. Conclusions and Relevance: Patients receiving ibrutinib as a first-line
      therapy for chronic lymphocytic leukemia and those without bulky disease had a
      better likelihood of CR to treatment. The CR rate with continued longer-term
      ibrutinib treatment was higher than in previous reports. Trial Registration:
      clinicaltrials.gov Identifiers: NCT01105247 and NCT01578707.

PMID- 29470587
TI  - New Geriatrics Legislation Promises a Better Present and Future for Us All as We
      Age.

PMID- 29470586
TI  - Implications of the CARE Act for Latino Caregivers.
AB  - The Caregiver Advise, Record, Enable (CARE) Act has the potential to make a
      positive impact in the lives of Latino older adults and their caregivers. As
      Latino individuals are the fastest growing older adult population, the number of
      Latino families and caregivers is also expected to grow, particularly among those
      providing care for someone with Alzheimer's disease or other dementias.
      Caregiving has been considered a culturally embedded value among Latino
      individuals. Although few studies have focused on caregiving in this population,
      those that exist suggest that Latino caregivers struggle to find bilingual and
      bicultural support and information and show higher levels of distress and health
      disparities. The purpose of the CARE Act is to help and support family caregivers
      when older adults are admitted to the hospital and during care transitions. The
      current article examines the potential implications of this state law,
      specifically on Latino individuals, including recommendations for policy
      implementation. [Journal of Gerontological Nursing, 44(3), 9-14.].

PMID- 29470588
TI  - [Extra-articular impingement of the hip : Treatment of snapping hip by
      lengthening of the iliotibial band].
AB  - OBJECTIVE: Snapping of the iliotibial band over the greater trochanter should be
      eliminated by reducing tension via lengthening, release, and incision of the
      iliotibial band. INDICATIONS: Positive clinical examination and painful snapping
      of the iliotibial band over the greater trochanter, despite extensive
      conservative treatments, for over 6 months. CONTRAINDICATIONS: Weakness of the
      abductor muscles with positive Trendelenburg sign. SURGICAL TECHNIQUE: Direct
      approach to the iliotibial tract. The snapping of the tract over the greater
      trochanter can be provoked and observed in situ via internal rotation and
      adduction of the hip. Lengthening of the iliotibial band is performed with a
      tongue-shape flap technique ("Griffelschachtelplastik") directly over the greater
      trochanter. This leads to simultaneous release and incision over the greater
      trochanter. Hereafter, no snapping of the tract should be observed upon motion
      analysis. POSTOPERATIVE MANAGEMENT: Pain-adapted mobilization with full
      weightbearing, no active abduction against resistance, and no adduction over and
      exceeding the 0-degree level for 6 weeks. RESULTS: The snapping of the iliotibial
      band could be eliminated in all cases. Apart from 2 patients with previous
      surgery who still complain of unimproved pain, improvement of symptoms with
      consequent subjective satisfaction with the outcome of surgery was reported in
      all cases.

PMID- 29470590
TI  - Correction to: Chronomedicine and type 2 diabetes: shining some light on
      melatonin.
AB  - The authors have been made aware that the following sentence is incorrect: 'Like
      IIK7, both ramelteon and tasimelteon have a greater affinity for the MT2 receptor
      [162].'

PMID- 29470589
TI  - Can insulin response patterns predict metabolic disease risk in individuals with
      normal glucose tolerance?

PMID- 29470591
TI  - [Differences in subjective health, mental health, and health behavior among 11-
      to 17-year-olds at secondary schools in Germany : Results of the German health
      interview and examination survey for children and adolescents: first follow-up
      (KiGGS Wave 1)].
AB  - BACKGROUND: Social inequalities in health can already be found among children and
      adolescents to the disadvantage of socially deprived population groups. This
      paper aims to detect, whether differences in subjective health, mental health and
      health behavior among young people are due to the secondary school type attended
      and whether these associations exist independently of the family's socioeconomic
      position (SEP). METHODS: The data basis was the German Health Interview and
      Examination Survey for Children and Adolescents (KiGGS Wave 1, 2009-2012). Data
      of 11- to 17-year-old girls and boys (n = 4665) who attend different types of
      secondary schools in Germany were analyzed. The dependent variables were self
      rated health, findings of the Strengths and Difficulties Questionnaire (SDQ) for
      the detection of psychological abnormalities, as well as self-reported
      information regarding leisure sport, tobacco, and alcohol consumption. Prevalence
      and odds ratios (ORs) based on logistic regressions are shown. RESULTS: For the
      majority of the examined indicators, it can be shown that adolescents in lower
      secondary schools are more likely to report worse self-rated health and mental
      problems and engage in unhealthy behavior than peers in grammar schools
      ("Gymnasium"). The differences decrease after controlling for family's SEP but
      mostly remain statistically significant. Adolescents who don't attend grammar
      schools are most strongly disadvantaged in terms of inattention/hyperactivity for
      both gender (OR: 2.29 [1.70-3.08]), smoking among girls (2.91 [1.85-4.57]) and
      physical inactivity (no leisure sport) among boys (OR: 2.71 [1.85-3.95]).
      DISCUSSION: Unequal health opportunities should be viewed in relation to people's
      living conditions. For adolescents, school constitutes an important setting for
      learning, experience, and health. The results indicate divergent needs of school
      based health promotion and prevention regarding differences among gender and type
      of school.

PMID- 29470592
TI  - [Treatment after anatomical and inverse shoulder TEP].
AB  - Shoulder arthroplasties in specialized centers are routine procedures with an
      increasing number of operations in the developed countries. Restoration of pain
      free shoulder function requires an intensive, specific and individual
      rehabilitation program for each patient. There is a phase-like course with
      different specific demands and measures that extends over a period of several
      weeks. Return to sport and a pain free function for activities of daily living
      resulting in a high patient satisfaction can routinely be expected. This
      excellent perspective, extent and intensity of the rehabilitation program shall
      be part of the preoperative decision making.

PMID- 29470594
TI  - Comments on Minisola et al.: Correction of vitamin D status by calcidiol:
      pharmacokinetic profile, safety, and biochemical effects on bone and mineral
      metabolism of daily and weekly dosage regimens.

PMID- 29470593
TI  - Increased Gi protein signaling potentiates the negative chronotropic effect of
      adenosine in the SHR right atrium.
AB  - Hypertension is a risk factor for cardiovascular diseases, which have been
      associated with dysfunction of sympathetic and purinergic neurotransmission.
      Therefore, herein, we evaluated whether modifications of adenosine receptor
      signaling may contribute to the cardiac dysfunction observed in hypertension.
      Isolated right atria from spontaneously hypertensive (SHR) or normotensive Wistar
      rats (NWR) were used to investigate the influence of adenosine receptor signaling
      cascade in the cardiac chronotropism. Our results showed that adenosine, the
      endogenous agonist of adenosine receptors, and CPA, a selective agonist of A1
      receptor, decreased the atrial chronotropism of NWR and SHR in a concentration-
      and time-dependent manner, culminating in cardiac arrest (0 bpm). Interestingly,
      a 3-fold lower concentration of adenosine was required to induce the negative
      chronotropic effect in SHR atria. Pre-incubation of tissues from both strains
      with DPCPX, a selective A1 receptor antagonist, inhibited the negative
      chronotropic effect of CPA, while simultaneous inhibition of A2 and A3 receptors,
      with ZM241385 and MRS1523, did not change the adenosine chronotropic effects.
      Moreover, 1 MUg/ml pertussis toxin, which inactivates the Galphai protein
      subunit, reduced by 80% the negative chronotropic effects of adenosine in the NWR
      atrium, with minor effects in SHR tissue. These data indicate that the negative
      chronotropic effect of adenosine in right atrium depends exclusively on the
      activation of A1 receptors. Moreover, the distinct responsiveness of NWR and SHR
      atria to pertussis toxin reveals that the enhanced negative chronotropic response
      of SHR right atrium is probably due to an increased activity of Galphai protein
      mediated.

PMID- 29470595
TI  - Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and
      biochemical effects on bone and mineral metabolism of daily and weekly dosage
      regimens: response to comments by Chen et al.

PMID- 29470596
TI  - Mental health burden in a national sample of American Indian and Alaska Native
      adults: differences between multiple-race and single-race subgroups.
AB  - PURPOSE: Research on American Indian and Alaska Native (AIAN) mental health
      disparities is based largely on either tribal populations or national samples of
      adults that do not account for multiracial AIANs, even though over 40% of AIANs
      identify with multiple racial groups. The present investigation extends this
      research by assessing mental health status in a national sample of multiracial
      AIAN adults relative to adults who identify exclusively as either AIAN or White.
      METHODS: 2012 BRFSS data were used to conduct multinomial logistic regression
      analyses comparing mental health outcomes among respondents who identified as
      either AIAN and one or more other races (AIAN-MR), AIAN-Single Race (AIAN-SR), or
      White-SR. RESULTS: After demographic adjustment, the AIAN-MR group reported a
      higher lifetime prevalence of diagnosed depressive disorder, more days of poor
      mental health, and more frequent mental distress compared to both the AIAN-SR and
      White-SR groups. AIAN-MR individuals also had higher levels of Kessler 6 (K6) non
      specific psychological distress compared to White-SR individuals but not AIAN-SR
      adults. Differences between AIAN-SR and White-SR adults were found in days of
      poor mental health, frequent mental distress, and total K6 scores. CONCLUSIONS:
      These findings help gauge the magnitude of mental health disparities in the U.S.
      AIAN population and pinpoint AIAN subgroups for whom mental health is
      particularly problematic. As such, they raise concerns about restrictions that
      limit the identification of national survey respondents who report multiple race
      designations. Such restrictions will thwart efforts to understand the causal
      mechanisms and pathways leading to mental distress among AIAN individuals.

PMID- 29470597
TI  - Mucosa-associated invariant T cells in malignancies: a faithful friend or
      formidable foe?
AB  - Mucosa-associated invariant T (MAIT) cells are a subset of innate-like T
      lymphocytes known for their ability to respond to MHC-related protein 1 (MR1)
      restricted stimuli and select cytokine signals. They are abundant in humans and
      especially enriched in mucosal layers, common sites of neoplastic transformation.
      MAIT cells have been found within primary and metastatic tumors. However, whether
      they promote malignancy or contribute to anticancer immunity is unclear. On the
      one hand, MAIT cells produce IL-17A in certain locations and under certain
      circumstances, which could in turn facilitate neoangiogenesis, intratumoral
      accumulation of immunosuppressive cell populations, and cancer progression. On
      the other hand, they can express a potent arsenal of cytotoxic effector
      molecules, NKG2D and IFN-gamma, all of which have established roles in cancer
      immune surveillance. In this review, we highlight MAIT cells' characteristics as
      they might pertain to cancer initiation, progression, or control. We discuss
      recent findings, including our own, that link MAIT cells to cancer, with a focus
      on colorectal carcinoma, as well as some of the outstanding questions in this
      active area of research. Finally, we provide a hypothetical picture in which MAIT
      cells constitute attractive targets in cancer immunotherapy.

PMID- 29470599
TI  - Metabolomics in Plant Stress Physiology.
AB  - Metabolomics is an essential technology for functional genomics and systems
      biology. It plays a key role in functional annotation of genes and understanding
      towards cellular and molecular, biotic and abiotic stress responses. Different
      analytical techniques are used to extend the coverage of a full metabolome. The
      commonly used techniques are NMR, CE-MS, LC-MS, and GC-MS. The choice of a
      suitable technique depends on the speed, sensitivity, and accuracy. This chapter
      provides insight into plant metabolomic techniques, databases used in the
      analysis, data mining and processing, compound identification, and limitations in
      metabolomics. It also describes the workflow of measuring metabolites in plants.
      Metabolomic studies in plant responses to stress are a key research topic in many
      laboratories worldwide. We summarize different approaches and provide a generic
      overview of stress responsive metabolite markers and processes compiled from a
      broad range of different studies. Graphical Abstract.

PMID- 29470598
TI  - Heterotopic ossification around the knee after tibial nailing and ipsilateral
      antegrade and retrograde femoral nailing in the treatment of floating knee
      injuries.
AB  - PURPOSE: Floating knee injuries are relatively uncommon injuries. We report the
      prevalence, location, and severity of heterotopic ossification (HO) around the
      knee in patients treated with antegrade tibial intramedullary nailing and
      ipsilateral antegrade versus retrograde femoral intramedullary nailing as well as
      how the severity of HO around the knee affects knee range of motion (ROM).
      METHODS: From 2004 to 2014, 26 floating knee injuries were included. Radiographs
      were reviewed to determine presence, location, and severity of HO. Post-operative
      knee ROM was determined. RESULTS: A significantly higher prevalence of HO around
      the knee was detected in the retrograde group (90%) compared to the antegrade
      group (43%) (p = 0.028). There was a trend for more HO into the patellar tendon
      occurring in 29% of patients in the antegrade group and 74% in the retrograde
      group (p = 0.069). The severity of HO was higher for the retrograde group 1.6 +/-
      1.0 compared to the antegrade group 0.4 +/- 0.5 (p = 0.004). There was poor
      correlation between HO severity and knee ROM. CONCLUSIONS: Treatment of floating
      knee injuries with a retrograde femoral nail was demonstrated to result in a
      greater likelihood of developing HO and a greater severity of HO around the knee
      than if treated with an antegrade femoral nail. However, this increased severity
      of HO is unlikely to affect ROM. LEVEL OF EVIDENCE: III.

PMID- 29470600
TI  - Genetic Mapping Populations for Conducting High-Resolution Trait Mapping in
      Plants.
AB  - Fine mapping of quantitative trait loci (QTL) is the route to more detailed
      molecular characterization and functional studies of the relationship between
      polymorphism and trait variation. It is also of direct relevance to breeding
      since it makes QTL more easily integrated into marker-assisted breeding and into
      genomic selection. Fine mapping requires that marker-trait associations are
      tested in populations in which large numbers of recombinations have occurred.
      This can be achieved by increasing the size of mapping populations or by
      increasing the number of generations of crossing required to create the
      population. We review the factors affecting the precision and power of fine
      mapping experiments and describe some contemporary experimental approaches,
      focusing on the use of multi-parental or multi-founder populations such as the
      multi-parent advanced generation intercross (MAGIC) and nested association
      mapping (NAM). We favor approaches such as MAGIC since these focus explicitly on
      increasing the amount of recombination that occurs within the population.
      Whatever approaches are used, we believe the days of mapping QTL in small
      populations must come to an end. In our own work in MAGIC wheat populations, we
      started with a target of developing 1,000 lines per population: that number now
      looks to be on the low side. Graphical Abstract.

PMID- 29470601
TI  - Expansionary Adaptive Transformations of Socio-Hydrological Systems (SHSs): The
      Case of Drought in Messara Plain, Crete, Greece.
AB  - The paper attempts to document the ontology of socio-hydrological systems (SHSs),
      propose approaches of delimitation of SHSs' (territorial) boundaries, and
      investigate operational aspects of their adaptation to drought including
      repercussions on sustainability. To this end, a series of hypotheses are tested:
      (a) SHSs contain social subsystems with different expectations regarding water
      resources, different adaptive capacities, adaptation limits and prospects of
      sustainability, (b) SHSs do not adapt homogenously; some of their subsystems
      manage optimum adaptation, others fail to adapt and (c) territorial
      transformation of SHSs (e.g., through expansion of SHSs) may be the result of
      differential adaptation and sustainability potential within the SHS owing to
      power relations. After testing above hypotheses in the SHS of Messara Plain,
      Crete, the authors found out that powerful and dynamic sub-SHSs expand or break
      the boundaries of the initial SHS by establishing new relationships with other
      SHSs for the sake of resilience resources. Conversely, powerless sub-SHSs
      incapable to adapt descend and disappear. Therefore, territorial transformation
      of SHSs comes about from a combination of successful and failed adaptations, or
      in other words from different adaptation limits within SHSs. Consequently, water
      management and local development planning to guarantee adaptability to drought
      for all should be based on SHSs' analysis and management, not on jurisdictional
      areas or hydrological basins.

PMID- 29470602
TI  - Who Really Wants an Ambitious Large-Scale Restoration of the Seine Estuary? A
      Strategic Analysis of a Science-Policy Interface Locked in a Stalemate.
AB  - The development of ecosystem knowledge is an essential condition for effective
      environmental management but using available knowledge to solve environmental
      controversies is still difficult in "real" situations. This paper explores the
      conditions under which ecological knowledge could contribute to the environmental
      strategies and actions of stakeholders at science-policy interface. Ecological
      restoration of the Seine estuary is an example of an environmental issue whose
      overall management has run into difficulties despite the production of a large
      amount of knowledge by a dedicated organization, GIP Seine Aval. Thanks to an
      action-research project, based on a futures study, we analyze the reasons of
      these difficulties and help the GIP Seine Aval adopt a robust strategy to
      overcome them. According to our results, most local stakeholders involved in the
      large-scale restoration project emphasize the need for a clear divide between
      knowledge production and environmental action. This kind of divide may be
      strategic in a context where the robustness of environmental decisions is
      strongly depending on the mobilization of "neutral" scientific knowledge. But in
      our case study, this rather blocks action because some powerful stakeholders
      continuously ask for more knowledge before taking action. The construction and
      analysis of possible future scenarios has led to three alternative strategies
      being identified to counter this stalemate situation: (1) to circumvent
      difficulties by creating indirect links between knowledge and actions; (2) to use
      knowledge to sustain advocacy for the interests of each and every stakeholder;
      (3) to involve citizens in decisions about knowledge production and use, so that
      environmental issues weight more on the local political agenda.

PMID- 29470603
TI  - Cardiac-gated intravoxel incoherent motion diffusion-weighted magnetic resonance
      imaging for the investigation of intracranial cerebrospinal fluid dynamics in the
      lateral ventricle: a feasibility study.
AB  - PURPOSE: Intravoxel incoherent motion (IVIM) in diffusion-weighted magnetic
      resonance imaging (DW-MRI) attributes the signal attenuation to the molecular
      diffusion and to a faster pseudo-diffusion. Purpose of the study was to
      demonstrate the feasibility of IVIM for the investigation of intracranial
      cerebrospinal fluid (CSF) dynamics. METHODS: Cardiac-gated DW-MRI images with
      fifteen b-values (0-1300s/mm2) along three orthogonal directions (mediolateral
      (ML), anteroposterior (AP), and craniocaudal (CC)) were acquired during maximum
      systole and diastole in 10 healthy volunteers (6 males, mean age 36 +/- 15
      years). A pixel-wise bi-exponential fitting with an iterative nonparametric
      algorithm was carried out to calculate the following parameters: diffusion
      coefficient (D), fast diffusion coefficient (D*), and fraction of fast diffusion
      (f). Region of interest measurements were performed in both lateral ventricles.
      Comparison of IVIM parameters was performed among two cardiac cycle acquisitions
      and among the diffusion-encoding directions using a paired Student's t test.
      RESULTS: f significantly (p < 0.05) depended on the diffusion-encoding direction
      and on the cardiac cycle (diastole AP 0.30 +/- 0.13, ML 0.22 +/- 0.12, CC 0.26 +/
      0.17; systole AP 0.45 +/- 0.17, ML 0.34 +/- 0.15, CC 0.40 +/- 0.21). Neither a
      cardiac cycle nor a direction dependency was found among mean D values (which is
      in line with the expected intraventricular isotropic diffusion) and D* values (p
      > 0.05 each). CONCLUSION: The fraction of fast diffusion from IVIM is feasible to
      detect a direction-dependent and cardiac-dependent pulsatile CSF flow within the
      lateral ventricles allowing for quantitative monitoring of CSF dynamics. This
      technique might provide opportunities to further investigate the pathophysiology
      of various neurological disorders involving altered CSF dynamics.

PMID- 29470604
TI  - Cathepsin H deficiency in mice induces excess Th1 cell activation and early-onset
      of EAE though impairment of toll-like receptor 3 cascade.
AB  - OBJECTIVE: The objective of this study is to investigate the role of cathepsin H
      (CatH), a lysosomal cysteine protease, in the development of experimental
      autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis.
      METHODS: EAE was induced in CatH-deficient mice (CatH-/-) and wild-type
      littermates (+/+) using myelin oligodendrocyte glycoprotein (MOG) 35-55. The
      effects of CatH deficiency were determined by clinical scoring, mRNA expression
      levels of Tbx21, Rorc and FoxP3, protein levels of poly(I:C)-induced toll-like
      receptor 3 (TLR3) and phosphorylation of IRF3, and secretion of interferon-beta
      (IFN-beta) by splenocytes. RESULTS AND CONCLUSIONS: CatH-/- showed a
      significantly earlier disease onset of EAE and increased Th1 cell differentiation
      in splenocytes. Splenocytes prepared from immunized CatH-/- showed a significant
      decrease in poly(I:C)-induced increased TLR3 expression, interferon regulatory
      factor 3 (IRF3) phospholylation and IFN-beta secretion. Therefore, CatH
      deficiency impaired TLR3-mediated activation of IRF3 and consequent secretion of
      IFN-beta from dendritic cells, leading to the enhancement of Th1 cell
      differentiation and consequent early disease onset of EAE.

PMID- 29470606
TI  - Anatomical and Histological Evaluation of the Retroauricular Fascia Flap for
      Staged Auricular Reconstruction.
AB  - OBJECTIVES: The retroauricular fascia flap (RFF) is one of the most commonly used
      vascularized linings for auriculocephalic sulcus reconstruction in staged total
      auricular reconstruction. This study aims to investigate the histomorphometric
      features regarding the retroauricular fascia. METHODS: Histological evaluation
      included qualitative observation and quantitative analysis of sections of RFF
      stained with hematoxylin and eosin, Masson's trichrome, Elastica van Gieson,
      CD31, and Lyve-1. Ultrasonographic evaluation included measurement of the
      thickness of the superficial layer of the retroauricular fascia (RFF origin) at
      three different positions in microtia patients. P < 0.05 was considered
      statistically significant. RESULTS: RFF was a thin, highly organized layer with
      mainly collagen fibers. From its superior to inferior portions, the percentage of
      collagen fibers differed significantly (superior 87.57 +/- 10.85%, middle 68.29
      +/- 29.02%, inferior 53.31 +/- 33.33%, p < 0.05). The percentages of elastic
      fibers in the superior (4.86 +/- 5.17%) and middle (5.05 +/- 5.37%) areas were
      higher than that in the inferior (2.14 +/- 2.42%, p < 0.05). RFF blood vessel
      density (20* magnification) decreased significantly from the superior to inferior
      portions (superior 6.39 +/- 1.18, middle 5.17 +/- 1.15, inferior 2.67 +/- 0.78, p
      < 0.05). Lymphatic vessel density (20* magnification) also decreased
      significantly from the superior to inferior regions (superior 6.80 +/- 0.62,
      middle 5.26 +/- 1.17, inferior 2.11 +/- 0.46, p < 0.05). Thickness of the
      superficial layer of retroauricular fascia increased significantly from the
      superior to inferior regions (superior 0.29 +/- 0.06 mm, middle 0.36 +/- 0.09 mm,
      inferior 0.53 +/- 0.14 mm, p < 0.001). CONCLUSIONS: From cranial to caudal, the
      RFF became thicker, less elastic, and less vascularized, and contained fewer
      lymphatic vessels. Therefore, when the retroauricular fascia is large enough, the
      superior portion would be preferred for RFF in auriculocephalic sulcus
      reconstruction. 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- 29470605
TI  - Considering the context: social factors in responses to drugs in humans.
AB  - BACKGROUND: Drugs are typically used in social settings. Here, we consider two
      factors that may contribute to this observation: (i) the presence of other people
      may enhance the positive mood effects of a drug, and conversely, (ii) drugs may
      enhance the value of social stimuli. METHODS: We review evidence from controlled
      laboratory studies with human volunteers, which investigated either of these
      interactions between social factors and responses to drugs. We examine the
      bidirectional effects of social stimuli and single doses of alcohol, stimulants,
      opioids, and cannabis. RESULTS: All four classes of drugs interact with social
      contexts, but the nature of these interactions varies across drugs, and depends
      on whether the context is positive or negative. CONCLUSIONS: Alcohol and
      stimulant drugs enhance the attractiveness of social stimuli and the desire to
      socialize, and social contexts, in turn, enhance these drugs' effects. In
      contrast, opioids and cannabis have subtler effects on social interactions and
      their effects are less influenced by the presence of others. Overall, there is
      stronger evidence that drugs enhance positive social contexts than that they
      dampen the negativity of unpleasant social settings. Controlled research is
      needed to understand the interactions between drugs of abuse and social contexts,
      to model and understand the determinants of drug use outside the laboratory.

PMID- 29470607
TI  - The Relationship Between Patients' Personality Traits and Breast Reconstruction
      Process.
AB  - BACKGROUND: Breast reconstruction after mastectomy is a part of breast cancer
      treatment. There is a lack of data regarding the impact of reconstruction over
      psychological traits and quality of life. The aim of this study is to evaluate
      personality changes in patients who underwent reconstructive surgery. METHODS:
      Thirty-seven women underwent breast reconstruction. These women took the Crown
      Crisp Experiential Index before and after the different procedures. The
      questionnaire analyzes: (a) the satisfaction level with personal relationships
      before and after surgery, and the level of satisfaction with surgical results and
      (b) personality index. Comparisons of preoperative and postoperative personality
      traits were made by using the Crown-Crisp test and analyzed by Chi-square test.
      Correlations between preoperative concerns and CCEI traits and correlations
      between physical aspects and Crown-Crisp, both preoperatively and
      postoperatively, were performed using the Spearman test. RESULTS: We found
      statistically significant differences in the following traits: anxiety
      anticipating possible technique failures (p = 0.01); cancer recurrence (p =
      0.04); dissatisfaction with results (p = 0.02); phobic anxiety for possible
      technique failure (p = 0.03); obsessionality with possible technique failure (p =
      0.01); preoccupations around cancer recurrence (p = 0.01) and dissatisfaction
      with results (p = 0.03); somatic of technique failure (p = 0.05); and finally,
      depression and hysteria traits in response to surgical procedures except
      anesthesia. CONCLUSION: This prospective study suggests that personality traits
      define perceptions of body image, which has an influence over quality of life and
      satisfaction with results. 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- 29470608
TI  - Bacterial Communities Inhabiting the Sponge Biemna fortis, Sediment and Water in
      Marine Lakes and the Open Sea.
AB  - Marine lakes are small bodies of landlocked seawater that are isolated from the
      open sea and have been shown to house numerous rare and unique taxa. The
      environmental conditions of the lakes are also characterised by lower pH and
      salinity and higher temperatures than generally found in the open sea. In the
      present study, we used a 16S rRNA gene barcoded pyrosequencing approach and a
      predictive metagenomic approach (PICRUSt) to examine bacterial composition and
      function in three distinct biotopes (sediment, water and the sponge species
      Biemna fortis) in three habitats (two marine lakes and the open sea) of the Berau
      reef system, Indonesia. Both biotope and habitat were significant predictors of
      higher taxon abundance and compositional variation. Most of the variation in
      operational taxonomic unit (OTU) composition was related to the biotope (42% for
      biotope alone versus 9% for habitat alone and 15% combined). Most OTUs were also
      restricted to a single biotope (1047 for B. fortis, 6120 for sediment and 471 for
      water). Only 98 OTUs were shared across all three biotopes. Bacterial communities
      from B. fortis, sediment and water samples were, however, also distinct in marine
      lake and open sea habitats. This was evident in the abundance of higher bacterial
      taxa. For example, the phylum Cyanobacteria was significantly more abundant in
      samples from marine lakes than from the open sea. This difference was most
      pronounced in the sponge B. fortis. In line with the compositional differences,
      there were pronounced differences in predicted relative gene count abundance
      among biotopes and habitats. Of particular interest was the predicted enrichment
      in B. fortis from the marine lakes for pathways including DNA replication and
      repair and the glutathione metabolism. This may facilitate adaptation of host and
      microbes to life in 'stressful' low pH, low salinity and/or high temperature
      environments such as those encountered in marine lakes.

PMID- 29470609
TI  - [New aspects in systemic treatment of atopic dermatitis].
AB  - In severe cases of atopic dermatitis (AD) systemic treatment is indicated. So
      far, cyclosporine and systemic glucocorticosteroids represented the only systemic
      treatment options approved for the indications of AD in Germany; however, from
      clinical practice there is increasing evidence for beneficial therapeutic effects
      in AD by other immunosuppressive or immunomodulatory substances, such as
      mycophenolate, methotrexate, alitretinoin and ustekinumab. Beyond this, ongoing
      research activities focus on a better understanding of genetic and immunological
      aspects of this chronic inflammatory skin disease. Regarding treatment with
      mycophenolate, genetic polymorphisms in AD patients could be identified that
      might predict responsiveness to this medication. Moreover, several new substances
      specifically targeting inflammation in AD are currently being studied and the
      first promising treatment effects on skin condition and pruritic symptoms of AD
      could be observed. As an exceptional result of this development in September 2017
      in Europe and therefore in Germany the first biologic as first-line treatment was
      approved for the indication of moderate to severe AD in adults. Dupilumab is a
      human monoclonal IgG4 antibody that blocks a subunit of the interleukin (IL)-4
      and IL-13 receptors, thus inhibiting the proinflammatory effects of these
      cytokines. Furthermore, the cytokine IL-13 itself, the IL-31 receptor, which is
      of particular relevance for pruritus in AD, the histamine-4-receptor and Janus
      kinases represent further promising targets currently being investigated in
      clinical trials for the treatment of AD.

PMID- 29470610
TI  - A comparison of new drugs approved by the FDA, the EMA, and Swissmedic: an
      assessment of the international harmonization of drugs.
AB  - INTRODUCTION: This study compared the characteristics of new human drugs approved
      by the Food and Drug Administration (FDA), the European Medicine Agency (EMA),
      and Swissmedic (SMC) in the period 2007 to 2016. METHODS: The list of new drugs
      and therapeutic biologics approved by the FDA, the EMA, and SMC in the period
      2007 to 2016 was collected from websites of those agencies. The study included
      regulatory information, approval date, and indication for each drug. Descriptive
      statistical t tests and x2-tests were performed for the analysis. RESULTS: From
      2007 to 2016, 134 new drugs were approved by all three regulatory agencies.
      Overall, 66.4% of the drugs were first approved by the FDA, 30.6% by the EMA, and
      3.0% by SMC. The difference in approval dates between SMC and the EMA, SMC and
      the FDA, and the FDA and the EMA were statistically significant. The indications
      approved by the FDA, the EMA, and SMC for the same drugs were similar in content
      for 23.1% drugs and different in 76.9% of the drugs. Significant differences in
      indications existed between the FDA and SMC and the FDA and the EMA, but not
      between the EMA and SMC. CONCLUSION: There were differences in the
      characteristics of new drugs approved by the EMA, the FDA, and SMC in the period
      2007-2016. Overall, two thirds of the new drugs were first approved by the FDA.
      Differences in indications were found in three out of four new drugs approved by
      the three regulatory agencies. Despite international drug regulation
      harmonization efforts, significant differences in the characteristics of new
      drugs approved by different agencies persist.

PMID- 29470611
TI  - Osteoporosis in Rheumatic Diseases: Anti-rheumatic Drugs and the Skeleton.
AB  - Osteoporosis in rheumatic diseases is a very well-known complication. Systemic
      inflammation results in both generalized and localized bone loss and erosions.
      Recently, increased knowledge of inflammatory process in rheumatic diseases has
      resulted in the development of potent inhibitors of the cytokines, the biologic
      DMARDs. These treatments reduce systemic inflammation and have some effect on the
      generalized and localized bone loss. Progression of bone erosion was slowed by
      TNF, IL-6 and IL-1 inhibitors, a JAK inhibitor, a CTLA4 agonist, and rituximab.
      Effects on bone mineral density varied between the biological DMARDs. Medications
      that are approved for the treatment of osteoporosis have been evaluated to
      prevent bone loss in rheumatic disease patients, including denosumab, cathepsin
      K, bisphosphonates, anti-sclerostin antibodies and parathyroid hormone (hPTH 1
      34), and have some efficacy in both the prevention of systemic bone loss and
      reducing localized bone erosions. This article reviews the effects of biologic
      DMARDs on bone mass and erosions in patients with rheumatic diseases and trials
      of anti-osteoporotic medications in animal models and patients with rheumatic
      diseases.

PMID- 29470612
TI  - Efficacy of aliskiren supplementation for heart failure : A meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Aliskiren might be beneficial for heart failure. However, the results
      of various studies are controversial. We conducted a systematic review and meta
      analysis to explore the efficacy of aliskiren supplementation for heart failure.
      METHODS: PubMed, Embase, Web of Science, EBSCO, and the Cochrane Library
      databases were systematically searched. Randomized controlled trials (RCTs)
      assessing the efficacy of aliskiren for heart failure were included. Two
      investigators independently searched for articles, extracted data, and assessed
      the quality of included studies. The meta-analysis was performed using the random
      effect model. RESULTS: Five RCTs comprising 1973 patients were included in the
      meta-analysis. Compared with control interventions in heart failure, aliskiren
      supplementation was found to significantly reduce NT-proBNP levels (standardized
      mean difference [SMD] = -0.12; 95% CI = -0.21 to -0.03 pg/ml; p = 0.008) and
      plasma renin activity (SMD = -0.66; 95% CI = -0.89 to -0.44 ng/ml.h; p < 0.00001)
      while increasing plasma renin concentration (SMD = 0.52; 95% CI = 0.30-0.75 ng/l;
      p < 0.00001); however, it demonstrated no significant influence on BNP levels
      (SMD = -0.08; 95% CI = -0.31-0.15 pg/ml; p = 0.49), mortality (RR = 0.97; 95% CI
      = 0.79-1.20; p = 0.79), aldosterone levels (SMD = -0.09; 95% CI = -0.32-0.14
      pmol/l; p = 0.44), adverse events (RR = 3.03; 95% CI = 0.18-49.51; p = 0.44), and
      serious adverse events (RR = 1.34; 95% CI = 0.54-3.33; p = 0.53). CONCLUSION:
      Aliskiren supplementation was found to significantly decrease NT-proBNP levels
      and plasma renin activity and to improve plasma renin concentration in the
      setting of heart failure.

PMID- 29470614
TI  - Roles of posttherapy 18F-FDG PET/CT in patients with advanced squamous cell
      carcinoma of the uterine cervix receiving concurrent chemoradiotherapy.
AB  - PURPOSE: To assess the clinical roles of [18F]fluorodeoxyglucose (18F-FDG)
      positron emission tomography/computed tomography (PET/CT) performed 2-3 months
      after completion of concurrent chemoradiotherapy (CCRT), along with pretherapy
      characteristics, in patients with advanced squamous cell carcinoma of the uterine
      cervix enrolled in a prospective randomized clinical trial. METHODS: Posttherapy
      PET/CT in patients with advanced FIGO stage or positive pelvic or para-aortic
      lymph node (PALN) defined on pretherapy PET/CT was classified as positive,
      equivocal, or negative. Overall survival (OS) rates between patients with
      different PET/CT results are compared. Pretherapy characteristics are examined
      for association with posttherapy PET/CT results and for prognostic significance
      in patients with equivocal or negative PET/CT. RESULTS: PET/CT scans (n = 55)
      were positive, equivocal and negative in 9, 13 and 33 patients, respectively. All
      patients with positive scans were confirmed to have residual or metastatic
      disease and died despite salvage therapies. There is a significant OS difference
      between patients with positive and equivocal scans (P < .001) but not between
      patients with equivocal and negative scans (P = .411). Positive pretherapy PALN
      is associated with positive posttherapy PET/CT (P = .033) and predicts a poorer
      survival in patients with equivocal or negative posttherapy PET/CT (P < .001).
      CONCLUSIONS: Positive PET/CT 2-3 months posttherapy implies treatment failure and
      novel therapy is necessary to improve outcomes for such patients. A more intense
      posttherapy surveillance may be warranted in patients with positive pretherapy
      PALN.

PMID- 29470615
TI  - Pre-dosing with lilotomab prior to therapy with 177Lu-lilotomab satetraxetan
      significantly increases the ratio of tumor to red marrow absorbed dose in non
      Hodgkin lymphoma patients.
AB  - PURPOSE: 177Lu-lilotomab satetraxetan is a novel anti-CD37 antibody radionuclide
      conjugate for the treatment of non-Hodgkin lymphoma (NHL). Four arms with
      different combinations of pre-dosing and pre-treatment have been investigated in
      a first-in-human phase 1/2a study for relapsed CD37+ indolent NHL. The aim of
      this work was to determine the tumor and normal tissue absorbed doses for all
      four arms, and investigate possible variations in the ratios of tumor to organs
      at-risk absorbed doses. METHODS: Two of the phase 1 arms included cold lilotomab
      pre-dosing (arm 1 and 4; 40 mg fixed and 100 mg/m2 BSA dosage, respectively) and
      two did not (arms 2 and 3). All patients were pre-treated with different regimens
      of rituximab. The patients received either 10, 15, or 20 MBq 177Lu-lilotomab
      satetraxetan per kg body weight. Nineteen patients were included for dosimetry,
      and a total of 47 lesions were included. The absorbed doses were calculated from
      multiple SPECT/CT-images and normalized by administered activity for each
      patient. Two-sided Student's t tests were used for all statistical analyses.
      RESULTS: Organs with distinct uptake of 177Lu-lilotomab satetraxetan, in addition
      to tumors, were red marrow (RM), liver, spleen, and kidneys. The mean RM absorbed
      doses were 0.94, 1.55, 1.44, and 0.89 mGy/MBq for arms 1-4, respectively. For the
      patients not pre-dosed with lilotomab (arms 2 and 3 combined) the mean RM
      absorbed dose was 1.48 mGy/MBq, which was significantly higher than for both arm
      1 (p = 0.04) and arm 4 (p = 0.02). Of the other organs, the highest uptake was
      found in the spleen, and there was a significantly lower spleen absorbed dose for
      arm-4 patients than for the patient group without lilotomab pre-dosing (1.13 vs.
      3.20 mGy/MBq; p < 0.01). Mean tumor absorbed doses were 2.15, 2.31, 1.33, and
      2.67 mGy/MBq for arms 1-4, respectively. After averaging the tumor absorbed dose
      for each patient, the patient mean tumor absorbed dose to RM absorbed dose ratios
      were obtained, given mean values of 1.07 for the patient group not pre-dosed with
      lilotomab, of 2.16 for arm 1, and of 4.62 for arm 4. The ratios were
      significantly higher in both arms 1 and 4 compared to the group without pre
      dosing (p = 0.05 and p = 0.02). No statistically significant difference between
      arms 1 and 4 was found. CONCLUSIONS: RM is the primary dose-limiting organ for
      177Lu-lilotomab satetraxetan treatment, and pre-dosing with lilotomab has a
      mitigating effect on RM absorbed dose. Increasing the amount of lilotomab from 40
      mg to 100 mg/m2 was found to slightly decrease the RM absorbed dose and increase
      the ratio of tumor to RM absorbed dose. Still, both pre-dosing amounts resulted
      in significantly higher tumor to RM absorbed dose ratios. The findings encourage
      continued use of pre-dosing with lilotomab.

PMID- 29470616
TI  - Automated SPECT analysis compared with expert visual scoring for the detection of
      FFR-defined coronary artery disease.
AB  - PURPOSE: Traditionally, interpretation of myocardial perfusion imaging (MPI) is
      based on visual assessment. Computer-based automated analysis might be a simple
      alternative obviating the need for extensive reading experience. Therefore, the
      aim of the present study was to compare the diagnostic performance of automated
      analysis with that of expert visual reading for the detection of obstructive
      coronary artery disease (CAD). METHODS: 206 Patients (64% men, age 58.2 +/- 8.7
      years) with suspected CAD were included prospectively. All patients underwent
      99mTc-tetrofosmin single-photon emission computed tomography (SPECT) and invasive
      coronary angiography with fractional flow reserve (FFR) measurements. Non
      corrected (NC) and attenuation-corrected (AC) SPECT images were analyzed both
      visually as well as automatically by commercially available SPECT software.
      Automated analysis comprised a segmental summed stress score (SSS), summed
      difference score (SDS), stress total perfusion deficit (S-TPD), and ischemic
      total perfusion deficit (I-TPD), representing the extent and severity of
      hypoperfused myocardium. Subsequently, software was optimized with an
      institutional normal database and thresholds. Diagnostic performances of
      automated and visual analysis were compared taking FFR as a reference. RESULTS:
      Sensitivity did not differ significantly between visual reading and most
      automated scoring parameters, except for SDS, which was significantly higher than
      visual assessment (p < 0.001). Specificity, however, was significantly higher for
      visual reading than for any of the automated scores (p < 0.001 for all).
      Diagnostic accuracy was significantly higher for visual scoring (77.2%) than for
      all NC images scores (p < 0.05), but not compared with SSS AC and S-TPD AC (69.8%
      and 71.2%, p = 0.063 and p = 0.134). After optimization of the automated
      software, diagnostic accuracies were similar for visual (73.8%) and automated
      analysis. Among the automated parameters, S-TPD AC showed the highest accuracy
      (73.5%). CONCLUSION: Automated analysis of myocardial perfusion SPECT can be as
      accurate as visual interpretation by an expert reader in detecting significant
      CAD defined by FFR.

PMID- 29470617
TI  - Effects of the Razor Clam Tagelus plebeius on the Fate of Petroleum Hydrocarbons:
      A Mesocosm Experiment.
AB  - The relationship between organisms and contaminants may be a two-way interaction:
      contaminants affecting the biota and the biota affecting the environmental fate
      and distribution of the contaminants. This may be especially so for sediment
      dwelling organisms, because their burrowing and feeding can drastically influence
      sediment characteristics. The present study looked at the influence of the
      suspension-feeding stout razor clam Tagelus plebeius on the distribution of crude
      oil and pyrene in greenhouse mesocosm experiments. Water column turbidity and
      sediment redox also were monitored during the 15- to 30-day exposures to provide
      information on the influence of hydrocarbons and the razor clams on environmental
      conditions. For the experiment with crude oil, sediment was taken from the
      mesocosms at the end of the experiment, and the hydrocarbon-degradation potential
      was assessed in incubations with 14C-naphthalene. The experiments used four
      treatments: hydrocarbons present/absent and razor clams present/absent.
      Hydrocarbon dosing levels were relatively low (1 mL of oil or 30 mg of pyrene per
      mesocosm with 22 L of natural sediment and 11 L of seawater). The presence of the
      razor clams resulted in hydrocarbon concentrations at the sediment surface being
      25% lower than in mesocosms without clams. No consistent effects were noted for
      polycyclic aromatic hydrocarbon (PAH) concentrations in the water column or in
      subsurface sediment. The naphthalene-degradation potential was elevated for
      sediment from mesocosms dosed with oil, but the presence of the clams did not
      affect this potential. The presence of the razor clams resulted in a lowering of
      water column turbidity, but no effect on sediment redox. The hydrocarbon addition
      had no effect on turbidity, but sediment redox was lowered. While results show
      that the presence of the razor clams resulted in a loss of hydrocarbons from the
      surface sediment, the other results do not provide a clear picture of the
      underlying mechanisms and the fate of the PAHs lost from the sediment surface. We
      hypothesize that the loss of surface sediment PAHs was due to burial of surface
      sediment and possibly bioaccumulation by the clams. While additional research is
      needed for further insights into underlying mechanisms, the present work
      demonstrates that the presence of sediment-burrowing suspension feeders decreases
      hydrocarbon levels in surface sediment. This means that assessments of the impact
      of an oil spill should pay attention to effects on these organisms and to their
      influence on the fate and distribution of the spilled oil.

PMID- 29470618
TI  - Tuning of acyl-ACP thioesterase activity directed for tailored fatty acid
      synthesis.
AB  - Medium-chain fatty acids have attracted significant attention as sources of
      biofuels in recent years. Acyl-ACP thioesterase, which is considered as the key
      enzyme to determine the carbon chain length, catalyzes the termination of de novo
      fatty acid synthesis. Although recombinant medium-chain acyl-ACP thioesterase
      (TE) affects the fatty acid profile in heterologous cells, tailoring of the fatty
      acid composition merely by engineering a specific TE is still intractable. In
      this study, the activity of a C8-C10-specific thioesterase FatB2 from Cuphea
      hookeriana on C10-ACP was quantified twice as high as that on C8-ACP based on a
      synthetic C8-C16 acyl-ACP pool in vitro. Whereas in vivo, it was demonstrated
      that ChFatB2 preferred to accumulate C8 fatty acids with 84.9% composition in the
      ChFatB2-engineered E. coli strain. To achieve C10 fatty acid production, ChFatB2
      was rationally tuned based on structural investigation and enzymatic analysis. An
      I198E mutant was identified to redistribute the C8-ACP flow, resulting in C10
      fatty acid being produced as the principal component at 57.6% of total fatty
      acids in vivo. It was demonstrated that the activity of TE relative to beta
      ketoacyl-ACP synthases (KAS) directly determined the fatty acid composition. Our
      results provide a prospective strategy in tailoring fatty acid synthesis by
      tuning of TE activities based on TE-ACP interaction.

PMID- 29470619
TI  - Exploring the sequence diversity in glycoside hydrolase family 13_18 reveals a
      novel glucosylglycerol phosphorylase.
AB  - In the carbohydrate-active enzyme database, GH13_18 is a family of retaining
      glycoside phosphorylases that act on alpha-glucosides. In this work, we explored
      the functional diversity of this family by comparing distinctive sequence motifs
      in different branches of its phylogenetic tree. A glycoside phosphorylase from
      Marinobacter adhaerens HP15 that was predicted to have a novel function was
      expressed and characterised. The enzyme was found to catalyse the reversible
      phosphorolysis of 2-O-alpha-D-glucosylglycerol with retention of the anomeric
      configuration, a specificity that has never been described before. Homology
      modelling, docking and mutagenesis were performed to pinpoint particular acceptor
      site residues (Tyr194, Ala333, Gln336) involved in the binding of glycerol. The
      new enzyme specificity provides additional insights into bacterial metabolic
      routes, being the first report of a phosphorolytic route for glucosylglycerol in
      a glucosylglycerol-producing organism. Furthermore, glucosylglycerol
      phosphorylase might be an attractive biocatalyst for the production of the
      osmolyte glucosylglycerol, which is currently produced on industrial scale by
      exploiting a side activity of the closely related sucrose phosphorylase. Family
      GH13_18 has clearly proven to be more diverse than was initially assumed, and the
      analysis of specificity-determining sequence motifs has shown to be a
      straightforward and fruitful tool for enzyme discovery.

PMID- 29470620
TI  - Dengue viruses and promising envelope protein domain III-based vaccines.
AB  - Dengue viruses are emerging mosquito-borne pathogens belonging to Flaviviridae
      family which are transmitted to humans via the bites of infected mosquitoes Aedes
      aegypti and Aedes albopictus. Because of the wide distribution of these mosquito
      vectors, more than 2.5 billion people are approximately at risk of dengue
      infection. Dengue viruses cause dengue fever and severe life-threatening
      illnesses as well as dengue hemorrhagic fever and dengue shock syndrome. All four
      serotypes of dengue virus can cause dengue diseases, but the manifestations are
      nearly different depending on type of the virus in consequent infections.
      Infection by any serotype creates life-long immunity against the corresponding
      serotype and temporary immunity to the others. This transient immunity declines
      after a while (6 months to 2 years) and is not protective against other
      serotypes, even may enhance the severity of a secondary heterotypic infection
      with a different serotype through a phenomenon known as antibody-depended
      enhancement (ADE). Although, it can be one of the possible explanations for more
      severe dengue diseases in individuals infected with a different serotype after
      primary infection. The envelope protein (E protein) of dengue virus is
      responsible for a wide range of biological activities, including binding to host
      cell receptors and fusion to and entry into host cells. The E protein, and
      especially its domain III (EDIII), stimulates host immunity responses by inducing
      protective and neutralizing antibodies. Therefore, the dengue E protein is an
      important antigen for vaccine development and diagnostic purposes. Here, we have
      provided a comprehensive review of dengue disease, vaccine design challenges, and
      various approaches in dengue vaccine development with emphasizing on newly
      developed envelope domain III-based dengue vaccine candidates.

PMID- 29470621
TI  - Novel sources of resistance to Septoria nodorum blotch in the Vavilov wheat
      collection identified by genome-wide association studies.
AB  - KEY MESSAGE: The fungus Parastagonospora nodorum causes Septoria nodorum blotch
      (SNB) of wheat. A genetically diverse wheat panel was used to dissect the
      complexity of SNB and identify novel sources of resistance. The fungus
      Parastagonospora nodorum is the causal agent of Septoria nodorum blotch (SNB) of
      wheat. The pathosystem is mediated by multiple fungal necrotrophic effector-host
      sensitivity gene interactions that include SnToxA-Tsn1, SnTox1-Snn1, and SnTox3
      Snn3. A P. nodorum strain lacking SnToxA, SnTox1, and SnTox3 (toxa13) retained
      wild-type-like ability to infect some modern wheat cultivars, suggesting evidence
      of other effector-mediated susceptibility gene interactions or the lack of host
      resistance genes. To identify genomic regions harbouring such loci, we examined a
      panel of 295 historic wheat accessions from the N. I. Vavilov Institute of Plant
      Genetic Resources in Russia, which is comprised of genetically diverse landraces
      and breeding lines registered from 1920 to 1990. The wheat panel was subjected to
      effector bioassays, infection with P. nodorum wild type (SN15) and toxa13. In
      general, SN15 was more virulent than toxa13. Insensitivity to all three effectors
      contributed significantly to resistance against SN15, but not toxa13. Genome-wide
      association studies using phenotypes from SN15 infection detected quantitative
      trait loci (QTL) on chromosomes 1BS (Snn1), 2DS, 5AS, 5BS (Snn3), 3AL, 4AL, 4BS,
      and 7AS. For toxa13 infection, a QTL was detected on 5AS (similar to SN15), plus
      two additional QTL on 2DL and 7DL. Analysis of resistance phenotypes indicated
      that plant breeders may have inadvertently selected for effector insensitivity
      from 1940 onwards. We identify accessions that can be used to develop bi-parental
      mapping populations to characterise resistance-associated alleles for subsequent
      introgression into modern bread wheat to minimise the impact of SNB.

PMID- 29470623
TI  - Long-distance longitudinal prostate MRI quality assurance: from startup to 12
      months.
AB  - PURPOSE: To evaluate a 12-month long-distance prostate MRI quality assurance (QA)
      program. METHODS: The need for IRB approval was waived for this prospective
      longitudinal QA effort. One academic institution experienced with prostate MRI [~
      1000 examinations/year (Site 2)] partnered with a private institution 240 miles
      away that was starting a new prostate MRI program (Site 1). Site 1 performed all
      examinations (N = 249). Four radiologists at Site 1 created finalized reports,
      then sent images and reports to Site 2 for review on a rolling basis. One
      radiologist at Site 2 reviewed findings and exam quality and discussed results by
      phone (~ 2-10 minutes/MRI). In months 1-6 all examinations were reviewed. In
      months 7-12 only PI-RADS <= 2 and 'difficult' cases were reviewed. Repeatability
      was assessed with intra-class correlation (ICC). 'Clinically significant cancer'
      was Gleason >= 7. RESULTS: Image quality significantly (p < 0.001) improved after
      the first three months. Inter-rater agreement also improved in months 3-4 [ICC:
      0.849 (95% CI 0.744-0.913)] and 5-6 [ICC: 0.768 (95% CI 0.619-0.864)] compared to
      months 1-2 [ICC: 0.621 (95% CI 0.436-0.756)]. PI-RADS <= 2 examinations were
      reclassified PI-RADS >= 3 in 19% (30/162); of these, 23 had post-MRI histology
      and 57% (13/23) had clinically significant cancer (5.2% of 249). False-negative
      examinations [N = 18 (PI-RADS <= 2 and Gleason >= 7)] were more common at Site 1
      during months 1-6 [9% (14/160) vs. 4% (4/89)]. Positive predictive values for PI
      RADS >= 3 were similar. CONCLUSION: Remote quality assurance of prostate MRI is
      feasible and useful, enabling new programs to gain durable skills with minimal
      risk to patients.

PMID- 29470622
TI  - Genetic dissection of wheat panicle traits using linkage analysis and a genome
      wide association study.
AB  - KEY MESSAGE: Coincident regions on chromosome 4B for GW, on 5A for SD and TSS,
      and on 3A for SL and GNS were detected through an integration of a linkage
      analysis and a genome-wide association study (GWAS). In addition, six stable QTL
      clusters on chromosomes 2D, 3A, 4B, 5A and 6A were identified with high PVE% on a
      composite map. The panicle traits of wheat, such as grain number per spike and
      1000-grain weight, are closely correlated with grain yield. Superior and
      effective alleles at loci related to panicles developments play a crucial role in
      the progress of molecular improvement in wheat yield breeding. Here, we revealed
      several notable allelic variations of seven panicle-related traits through an
      integration of genome-wide association mapping and a linkage analysis. The
      linkage analysis was performed using a recombinant inbred line (RIL) population
      (173 lines of F8:9) with a high-density genetic map constructed with 90K SNP
      arrays, Diversity Arrays Technology (DArT) and simple sequence repeat (SSR)
      markers in five environments. Thirty-five additive quantitative trait loci (QTL)
      were discovered, including eleven stable QTLs on chromosomes 1A, 2D, 4B, 5B, 6B,
      and 6D. The marker interval between EX_C101685 and RAC875_C27536 on chromosome 4B
      exhibited pleiotropic effects for GW, SL, GNS, FSN, SSN, and TSS, with the
      phenotypic variation explained (PVE) ranging from 5.40 to 37.70%. In addition, an
      association analysis was conducted using a diverse panel of 205 elite wheat lines
      with a composite map (24,355 SNPs) based on the Illumina Infinium assay in four
      environments. A total of 73 significant marker-trait associations (MTAs) were
      detected for panicle traits, which were distributed across all wheat chromosomes
      except for 4D, 5D, and 6D. Consensus regions between RAC875_C27536_611 and
      Tdurum_contig4974_355 on chromosome 4B for GW in multiple environments, between
      QTSS5A.7-43 and BS00021805_51 on 5A for SD and TSS, and between QSD3A.2-164 and
      RAC875_c17479_359 on 3A for SL and GNS in multiple environments were detected
      through linkage analysis and a genome-wide association study (GWAS). In addition,
      six stable QTL clusters on chromosomes 2D, 3A, 4B, 5A, and 6A were identified
      with high PVE% on a composite map. This study provides potentially valuable
      information on the dissection of yield-component traits and valuable genetic
      alleles for molecular-design breeding or functional gene exploration.

PMID- 29470624
TI  - Measuring liver T2* and cardiac T2* in a single acquisition.
AB  - PURPOSE: The purpose of this study is determine if both liver T2* and cardiac T2*
      can be measured on a single breath-hold acquisition. MATERIALS AND METHODS: For
      this IRB-approved retrospective study, 137 patients with dedicated Cardiac MRI
      and Liver MRI examinations obtained sequentially on 1.5T scanners and on the same
      day were included for analysis. Both the cardiac and liver MRI examinations
      utilized GRE sequences for quantification of tissue iron. Specifically, T2* was
      measured using an 8-echo, multi-echo gradient echo single breath-hold sequence.
      Liver T2* was measured in a blinded manner on images from each of the cardiac and
      dedicated liver MRI examinations and were correlated. Bland-Altman difference
      plot was used to assess mean bias. RESULTS: 137 examinations from 93 subjects met
      inclusion criteria. 10 examination pairs were excluded because the first echo
      time (TE) on the cardiac MRI was insufficiently short for the very high liver
      iron content. After exclusion, 127 studies from 89 subjects (67.4% males) were
      included in the final analysis. The mean subject age (+/- standard deviation) was
      11.5 +/- 7.5 years (range 0-29.3 years; median 10.5 years). Mean liver T2*
      measured on cardiac MRI was 8.3 +/- 7.7 ms and mean liver T2* measured on
      dedicated liver MRI was 7.8 +/- 7.4 ms (p < 0.001). There was strong positive
      correlation between the two liver T2* measurements (r = 0.989, p < 0.0001; 95% CI
      0.985-0.992). With the exception of borderline outliers, all values fell within
      two standard deviations on the Bland-Altman difference plots, with a mean bias of
      0.5 ms (range - 1.8 to + 2.7 ms). CONCLUSION: In most patients with suspected or
      known iron overload, a single breath-hold GRE sequence may be sufficient to
      evaluate the iron concentration (T2*) of both the myocardium and the liver.

PMID- 29470625
TI  - Fluoroscopy-guided trans-anal decompression tube placement in the treatment of
      acute colonic pseudo-obstruction: a single center experience.
AB  - PURPOSE: Acute colonic pseudo-obstruction (ACPO or Ogilvie's syndrome) is a rare
      but often fatal disease; timely colonic decompression may be essential for
      successful treatment. This study describes a technique of placing a trans-anal
      tube via fluoroscopy-guiding and investigates the effect of colon decompression
      on ACPO. METHODS: Patients undergoing colonic decompression via fluoroscopy
      guided trans-anal tube placement from April 2015 to May 2017 were included. The
      technical and clinical successes of this procedure were evaluated. Clinical
      features and long-term outcomes are described. RESULTS: Decompression was
      successful in 72.73% (16/22) of the patients; the procedure was considered a
      clinical success in 50% (11/22) of the patients. 31.82% (7/22) of the patients
      underwent elective surgery, and only 18.19% (4/22) of the patients need emergency
      surgery. CONCLUSIONS: Fluoroscopy-guided trans-anal decompression tube placement
      was an easy and efficient method for treating ACPO. Additionally, ACPO once
      required emergency surgery, but now may only require elective surgery in certain
      instances.

PMID- 29470626
TI  - Living donor liver transplantation: post-operative imaging follow-up of right
      lobe liver donors.
AB  - PURPOSE: To identify long-term post-operative imaging findings resulting from
      right lobe liver donation. METHODS: This retrospective imaging review consisted
      of 42 adults (20 males, 22 females, mean age 36.6 years, range 18.7-55.9 years)
      who underwent right lobe liver donation with pre- and post-operative imaging
      between 1999 and 2006. The mean follow-up period was 30.2 months (range 12.3-69.6
      months). Follow-up imaging evaluation included assessment of the biliary tree,
      particularly isolated bile ducts draining to and terminating at the cut surface
      (orphan ducts). Three-dimensional volumetry of the liver remnant was also
      assessed. RESULTS: After liver donation, 29/42 (69%) participants demonstrated
      orphan ducts on follow-up imaging (95% confidence interval 52.9% to 82.4%). In
      those patients with orphan ducts, the main draining ducts were normal in 70% and
      dilated in 69%. Nearly all right lobe liver donors with orphan ducts had no
      clinical symptoms on follow-up (28/29); the only liver donor with clinical
      symptoms on follow-up was subsequently diagnosed with primary biliary cirrhosis.
      Mean regenerated liver volume was approximately 93%, with mean pre-operative
      total liver volume of 1552 ml (median 1504 ml, range 1040-2520 ml) and mean post
      operative total liver volume of 1446 ml (median 1455 ml, range 964-2090 ml).
      CONCLUSIONS: Orphan ducts are changes that may be seen after liver donation. The
      presence of these findings in the absence of clinical symptoms or abnormal
      hepatic chemistries does not require further work-up and should not be considered
      pathologic.

PMID- 29470627
TI  - Value of hepatocellular phase imaging after intravenous gadoxetate disodium for
      assessing hepatic metastases from gastroenteropancreatic neuroendocrine tumors:
      comparison with other MRI pulse sequences and with extracellular agent.
AB  - OBJECTIVE: To compare hepatocellular phase imaging after intravenous gadoxetate
      disodium with other MRI pulse sequences and with extracellular agent for
      assessing hepatic metastases from gastroenteropancreatic neuroendocrine neoplasms
      (GEP-NEN). MATERIALS AND METHODS: In this IRB-approved, HIPAA-compliant
      retrospective study, we included 30 patients (15 women, mean age: 58 years, range
      44-77 years) with GEP-NEN metastatic to the liver, who underwent MRI with
      gadoxetate disodium. Six MRI sequences were reviewed by two radiologists to score
      tumor-liver interface (TLI) on a 5-point scale, to assess lesion detectability in
      different liver segments (divided into 3 zones/patient), and to measure lesion
      size. Contrast-to-noise ratio (CNR) was calculated on each sequence. In 19
      patients, lesion size and CNR on dynamic imaging with gadopentetate dimeglumine
      was compared with hepatocellular phase. Wilcoxon signed-rank test was used to
      compare TLI scores, lesion size, and median CNR, using Bonferroni correction for
      multiple testing. Interobserver agreement for TLI was analyzed using
      Krippendorff's alpha, and for lesion size using concordance correlation
      coefficient (CCC) and mean relative difference. RESULTS: Hepatocellular phase had
      the best TLI (mean TLI for reader 1 = 1.2, reader 2 = 1.3) compared to all other
      sequences (p < 0.0001) with excellent interobserver agreement (Krippendorff's
      alpha = 1.0), maximum lesion detectability (61/90 zones), highest interobserver
      agreement for lesion measurement (CCC 0.9875 and smallest mean relative
      difference - 1.567%), and highest median CNR (31.2, p < 0.008). Hepatocellular
      phase also had the highest CNR when compared with gadopentetate imaging.
      CONCLUSION: Hepatocellular phase imaging offers significant advantages for
      assessment of hepatic metastasis in GEP-NEN, and should be routinely considered
      for follow-up of these patients.

PMID- 29470628
TI  - Bladder debris on ultrasound in the emergency department: correlation with
      urinalysis.
AB  - PURPOSE: To evaluate the correlation between the presence of bladder debris on
      ultrasound and urinalysis results in the emergency department setting. METHODS:
      Adult patients presenting to the emergency department with an ultrasound of the
      bladder and a urinalysis performed within 24 h of the ultrasound were included in
      this retrospective study. Two radiologists in consensus evaluated for the
      presence or absence of debris within the bladder. Urinalysis results were
      recorded including continuous variables (specific gravity and pH) and categorical
      variables (presence of occult blood, bilirubin, ketones, glucose, protein,
      urobilinogen, nitrite, leukocyte esterase, white blood cells, and red blood
      cells). The presence and absence of white and red blood cells were defined as > 5
      cells/high-powered field. To control the experimentwise type I error rate at
      0.05, a Bonferroni-corrected significance level of 0.0042 was used to determine
      significant associations. RESULTS: The presence of bladder debris was associated
      with the presence of urobilinogen, nitrite, and white blood cells (p = < 0.0001,
      0.0005, and 0.0004, respectively). CONCLUSIONS: Bladder debris in the emergency
      department setting correlates with urinalysis laboratory values suggesting a
      urinary tract infection. Therefore, the presence of bladder debris should elicit
      the recommendation of a urinalysis in such a setting.

PMID- 29470629
TI  - Adding ancillary features to enhancement patterns of hepatocellular carcinoma on
      gadoxetic acid-enhanced magnetic resonance imaging improves diagnostic
      performance.
AB  - PURPOSE: To assess the added value of intratumoral ancillary features to
      conventional enhancement pattern-based diagnosis of hepatocellular carcinoma
      (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: A total of 773 consecutive patients with surgically resected 773 primary
      hepatic tumors (699 HCCs, 63 intrahepatic cholangiocarcinomas, and 11 benign
      nodules) who underwent gadoxetic acid-enhanced MRI were retrospectively
      identified. Enhancement patterns and three ancillary features of capsule, septum,
      and T2 spotty hyperintensity were assessed by two radiologists. Performance of
      enhancement pattern-based diagnosis of HCC was compared to diagnosis of HCC based
      on enhancement pattern plus ancillary features. RESULTS: Enhancement patterns
      were positive (arterial diffuse hyperenhancement with washout) for 562 (72.7%)
      tumors, negative (no arterial hyperenhancement and no washout) for 75 (9.7%), and
      inconclusive (either no arterial hyperenhancement or no washout) for 136 (17.6%).
      Capsule was observed in 498 (64.4%) tumors, septum in 521 (67.3%), and T2 spotty
      hyperintensity in 107 (13.8%). The accuracy and sensitivity of HCC diagnosis was
      improved significantly after adding at least one ancillary feature compared with
      enhancement pattern-based diagnosis of HCCs (79.9% vs. 91.1% for accuracy, p <
      0.0001 and 79.1% vs. 92.0% for sensitivity, p < 0.0001) with a minor tradeoff in
      specificity (87.8% vs. 82.4%, p = 0.125). Adding at least two ancillary features
      improved accuracy (88.1%, p < 0.0001) and sensitivity (88.1%, p < 0.0001) without
      changing specificity (87.8%, p = 1.0). CONCLUSION: Adding intratumoral ancillary
      features of capsule, septum and T2 spotty hyperintensity to conventional
      enhancement patterns on gadoxetic acid-enhanced MRI improved accuracy and
      sensitivity, while maintaining specificity for HCC diagnosis.

PMID- 29470632
TI  - 2017 Acknowledgment of reviewers.

PMID- 29470631
TI  - Flavor perception and the risk of malnutrition in patients with Parkinson's
      disease.
AB  - Flavor perception involves both olfactory and gustatory function. In patients
      with Parkinson's disease (PD), hyposmia is a frequent finding, as well as an
      increased risk of malnutrition. We performed a pilot study to investigate the
      relationship between flavor perception and risk of malnutrition in PD patients.
      63 PD patients participated to perform an olfactory (Sniffin' Sticks) and
      gustatory (Taste Strips) task, and a questionnaire to establish nutritional risk
      (MUST), which includes BMI measurements. The relationship between olfactory and
      gustatory function and BMI was analyzed using partial correlations, corrected for
      disease duration, and regression analysis. Patients displayed a high prevalence
      of hyposmia (68.3%), and a low prevalence (6.3%) of hypogeusia. A small, but
      significant correlation was found between olfactory function and BMI (r = 0.261,
      p = 0.038), and not for gustatory function and BMI (r = 0.137, p = 0.284).
      Hyposmia, and not hypogeusia, may contribute to weight loss in Parkinson's
      disease, and hence increase the risk of malnutrition.

PMID- 29470630
TI  - Modified ante situm liver resection without use of cold perfusion nor veno-venous
      bypass for treatment of hepatic lesions infiltrating the hepatocaval confluence.
AB  - PURPOSE: Treatment of malignancies invading the hepatic veins/inferior vena cava
      is a surgical challenge. An ante situm technique allows luxation of the liver in
      front of the situs to perform tumor resection. Usually, cold perfusion and veno
      venous bypass are applied. Our experience with modified ante situm resection
      relying only on total vascular occlusion is reported. METHODS: Retrospective
      analysis on an almost 15-year experience with ante situm resection without
      application of cold perfusion or veno-venous bypass RESULTS: The ante situm
      technique was applied on eight patients. Five individuals were treated due to
      intrahepatic cholangiocellular cancer and one case each for mixed cholangio
      /hepatocellular carcinoma, colorectal liver metastasis, and pheochromocytoma.
      Trisectorectomy (n = 4), left hemihepatectomy, right hepatectomy, atypical
      resection, or mesohepatectomy (each n = 1) were performed, combined with
      dissection of suprahepatic/retrohepatic vena cava/hepatic veins. Venous
      reconstruction was achieved by reimplantation of hepatic veins with/without
      vascular replacement using allogeneic donor veins or PTFE grafts. Median total
      vascular occlusion of the liver was 23 min. Severe morbidity occurred in three
      patients (Dindo-Clavien > 3A). R0 status was achieved in six cases with a median
      overall survival of 33.5 months. CONCLUSIONS: Ante situm liver resection can be
      applied without cold perfusion nor veno-venous bypass with acceptable morbidity
      and mortality. However, this procedure remains challenging even for the
      experienced hepato-pancreato-biliary surgeon.

PMID- 29470633
TI  - Feasibility of a novel laparoscopic technique with unidirectional knotless barbed
      sutures for the primary closure of duodenal ulcer perforation.
AB  - BACKGROUND: Laparoscopic primary repair is one of the main procedures used for
      perforated gastric ulcers, and this technique requires reproducible and secure
      suturing. The aim of this study was to investigate the safety and efficacy of a
      novel continuous suture method with barbed sutures during laparoscopic repair for
      perforated peptic ulcers. PATIENTS AND METHODS: Clinical data from 116
      consecutive patients undergoing laparoscopic repair for perforated peptic ulcers
      were collected between November 2009 and October 2015. Continuous suturing with
      15-cm-long unidirectional absorbable barbed sutures was used for laparoscopic
      repair in the study group, termed group V (n = 51). Patients who underwent
      laparoscopic repair with conventional interrupted sutures were defined as group C
      (n = 65). The complication and operative data were compared between groups.
      RESULTS: Although there was no difference between group V and group C in the
      overall complication rate (15.7% vs. 24.6%; p = 0.259), the complication rate
      related to suturing was lower (3.9% vs. 15.4%; p = 0.04) in group V. Group V
      showed rates of 0% for leakage, 2% for intra-abdominal fluid collection, and 2%
      for stricture; the corresponding rates in group C were 3.1, 7.7, and 4.6%,
      respectively. Regarding operative data, the total operation time (V vs. C, 87.7
      min vs. 131.2 min), total suture time (7.1 min vs. 25.3 min), and suture time per
      stitch (1.2 min vs. 6.2 min) were significantly shorter in group V than in group
      C (p < 0.001). CONCLUSION: The use of a continuous suture technique with
      unidirectional barbed sutures is as safe as the conventional suture technique and
      allows easier and faster suturing in the repair of perforated peptic ulcers.

PMID- 29470634
TI  - Detection of Bacterial DNA During the Process of Sake Production Using Sokujo
      Moto.
AB  - There are two types of starter cultures used in Japanese rice wine (sake)
      fermentation, namely, sokujo-moto and yamahai-moto. Analyses of microbiota
      changes during sake production using yamahai-moto have already been reported. In
      this study, we analyzed microbiota changes during sake production using sokujo
      moto. In addition, we sequenced bacterial DNA from the water used in sake
      production. The Lactobacillus DNA sequences, which are frequently detected during
      sake production using yamahai-moto, were not detected during sake production
      using sokujo-moto, indicating that the Lactobacillus DNA detected in sakes made
      from yamahai-moto is from the fermentation starter. Most bacterial DNA sequences
      detected in water were not found in the production samples of sake suggesting
      that these bacteria do not proliferate during sake production. Thus, most of the
      bacterial DNA sequences detected during the production may be from the bacterial
      contamination during the production process.

PMID- 29470635
TI  - Distribution, sources, and toxicity assessment of polycyclic aromatic
      hydrocarbons in surface soils of a heavy industrial city, Liuzhou, China.
AB  - As a heavy industrial city, Liuzhou has been facing a serious pollution problem.
      It is necessary to take steps to control and prevent environmental pollution
      wherever possible. Surface soil samples were collected from four communities in
      Liuzhou City, to determine the concentrations, distributions, sources, and
      toxicity potential of polycyclic aromatic hydrocarbons (PAHs) present. The mean
      concentrations of total PAHs in the surface soil are 756.43 ng/g for the heavy
      industrial area, 605.06 ng/g for the industrial area, 481.24 ng/g for the
      commercial-cum-residential area, and 49.93 ng/g for the rural area. Both the
      isomer ratio and principal component analyses for the PAHs prove that these
      pollutants originate mainly from coal, diesel, gasoline, and natural gas
      combustion. The pollution hierarchies and toxic equivalency factor of BaP prove
      that the city is subject to heavy pollution caused by industry, transportation,
      and daily human activities.

PMID- 29470636
TI  - Migration background and childhood overweight in the Hannover Region in 2010
      2014: a population-based secondary data analysis of school entry examinations.
AB  - : Overweight and obesity constitute a global epidemic with rates that are
      increasing rapidly in children. The aim of the present study was to examine
      ethnic differences in the prevalence of overweight in pre-school children in a
      multicultural context. Data were collected from a compulsory school entry
      examination in the Hannover Region, Germany (n = 50,716) from 2010 to 2014. The
      prevalence of overweight (including pre-obesity and obesity status) and obesity
      was estimated using a German national reference. The migration status of the
      children was based on the parent's migration history. Multivariable logistic and
      hierarchical multinomial regression analyses were performed to identify factors
      associated with the overweight, pre-obesity, and obesity status. The prevalence
      of overweight was significantly higher among migrant children (12.7%) than among
      the non-migrant children (6.9%). After adjusting for socioeconomic and child
      development variables, migration background was strongly associated with weight
      status. The Turkish migrant children showed the highest odds of being pre-obesity
      (OR 2.05, 95%CI 1.7-2.56) and obesity (OR 2.09, 95%CI 1.67-2.77) compared to non
      migrant children. CONCLUSION: Ethnic and social inequalities exist in childhood
      overweight among pre-school children in the Hannover Region. Thus, appropriate
      interventions targeting high-risk migrant groups are needed. What is Known: * The
      current trend of prevalence rates in Germany for overweight and obesity of pre
      school children is becoming stable. * Prevalence of overweight and obesity is
      clearly higher among migrant children than among non-migrant children. What is
      New: * This article reveals ethnic variance among different migrant groups. *
      Turkish migrant children have a higher rate of prevalence even compared to other
      migrant groups. * Length of child day care attendance fails to exert a strong
      influence on overweight after adjusting for socio-economic and child development
      variables.

PMID- 29470637
TI  - A higher association of medial collateral ligament injury of the knee in
      pronation injuries of the ankle.
AB  - INTRODUCTION: To evaluate the prevalence of medial collateral ligament (MCL)
      injury of the knee among ankle-fracture patients and to determine the risk
      factors associated with MCL injury in this patient group. MATERIALS AND METHODS:
      303 patients (303 affected ankles) who underwent surgical treatment for an ankle
      fracture were assessed. Supination versus pronation injury, Danis-Weber
      classification, age, sex, body mass index (BMI), limb dominance, and mechanism of
      injury were reviewed to identify factors related to MCL injury. RESULTS:
      Prevalence of MCL injury of the knee among the total number of patients with an
      ankle fracture was 3.96% (12 out of 303 injuries). Multivariable logistic and
      linear regression analysis with adjustment of possible confounding factors
      confirmed that female sex and pronation injury were associated significantly (p <
      0.05) with MCL injury. CONCLUSIONS: The prevalence of MCL injury among females
      and the pronation type of ankle injury was 8.19% (10 out of 122 females) and
      10.75% (10 out of 93 pronation injuries), respectively. More careful physical
      examination of the knee joint is strongly recommended in patients with ankle
      fractures, especially if the patient is female or the ankle-fracture pattern
      corresponds to the pronation type of injury.

PMID- 29470638
TI  - Long-term effects of low-dose mouse liver irradiation involve ultrastructural and
      biochemical changes in hepatocytes that depend on lipid metabolism.
AB  - The aim of the study was to investigate long-term effects of radiation on the
      (ultra)structure and function of the liver in mice. The experiments were
      conducted on wild-type C57BL/6J and apolipoprotein E knock-out (ApoE-/-) male
      mice which received a single dose (2 or 8 Gy) of X-rays to the heart with
      simultaneous exposure of liver to low doses (no more than 30 and 120 mGy,
      respectively). Livers were collected for analysis 60 weeks after irradiation and
      used for morphological, ultrastructural, and biochemical studies. The results
      show increased damage to mitochondrial ultrastructure and lipid deposition in
      hepatocytes of irradiated animals as compared to non-irradiated controls.
      Stronger radiation-related effects were noted in ApoE-/- mice than wild-type
      animals. In contrast, radiation-related changes in the activity of lysosomal
      hydrolases, including acid phosphatase, beta-glucuronidase, N-acetyl-beta-D
      hexosaminidase, beta-galactosidase, and alpha-glucosidase, were observed in wild
      type but not in ApoE-deficient mice, which together with ultrastructural picture
      suggests a higher activity of autophagy in ApoE-proficient animals. Irradiation
      caused a reduction of plasma markers of liver damage in wild-type mice, while an
      increased level of hepatic lipase was observed in plasma of ApoE-deficient mice,
      which collectively indicates a higher resistance of hepatocytes from ApoE
      proficient animals to radiation-mediated damage. In conclusion, liver
      dysfunctions were observed as late effects of irradiation with an apparent
      association with malfunction of lipid metabolism.

PMID- 29470639
TI  - Arabinogalactan proteins and their sugar chains: functions in plant reproduction,
      research methods, and biosynthesis.
AB  - The arabinogalactan protein (AGP) family is one of the most complex protein
      families and is ubiquitous in the plant kingdom. Moreover, it has been
      demonstrated to play various roles during plant reproduction. A typical AGP
      contains a hydroxyproline-rich core protein with high heterogeneity and varying
      numbers of polysaccharide side chains. However, the functions of the
      polysaccharide components (i.e. AG sugar chains) remain largely unknown due to
      the general difficulties associated with studying sugar chains in glycobiology.
      In recent years, methodological breakthroughs have resulted in substantial
      progress in AGP research. Here, we summarise the multiple roles of AGPs during
      plant gametophyte development and male-female communication, with a focus on
      recent advances. In addition, we discuss the analytical tools used in AGP
      research, and the biosynthesis and function of AG sugar chains. A comprehensive
      understanding of the AGP family will help clarify the mechanisms precisely
      controlling reproductive processes.

PMID- 29470641
TI  - Acid-base balance during muscular exercise: response to Dr. Boning and Dr.
      Maassen.

PMID- 29470640
TI  - Quantitative susceptibility mapping in combination with water-fat separation for
      simultaneous liver iron and fat fraction quantification.
AB  - PURPOSES: To evaluate the feasibility of simultaneous quantification of liver
      iron concentration (LIC) and fat fraction (FF) using water-fat separation and
      quantitative susceptibility mapping (QSM). METHODS: Forty-five patients suspected
      of liver iron overload (LIO) were included. A volumetric interpolated breath-hold
      examination sequence for QSM and FF, a fat-saturated gradient echo sequence for
      R2*, a spin echo sequence for LIC measurements and MRS analyses for FF (FF-MRS)
      were performed. Magnetic susceptibility and FF were calculated using a water-fat
      separation method (FF-MRI). Correlation and receiver operating characteristic
      analyses were performed. RESULTS: Magnetic susceptibility showed strong
      correlation with LIC (rs=0.918). The optimal susceptibility cut-off values were
      0.34, 0.63, 1.29 and 2.23 ppm corresponding to LIC thresholds of 1.8, 3.2, 7.0
      and 15.0 mg/g dry weight. The area under the curve (AUC) were 0.948, 0.970, 1 and
      1, respectively. No difference in AUC was found between susceptibility and R2* at
      all LIC thresholds. Correlation was found between FF-MRI and FF-MRS (R2=0.910).
      CONCLUSIONS: QSM has a high diagnostic performance for LIC quantification,
      similar to that of R2*. FF-MRI provides simultaneous fat quantification. Findings
      suggest QSM in combination with water-fat separation has potential value for
      evaluating LIO, especially in cases with coexisting steatosis. KEY POINTS: *
      Magnetic susceptibility showed strong correlation with LIC (r s =0.918). * QSM
      showed high diagnostic performance for LIC, similar to that of R 2* . *
      Simultaneously estimated FF-MRI showed strong correlation with MR-Spectroscopy
      based FF (R 2 =0.910). * QSM combining water-fat separation has quantitative
      value for LIO with coexisted steatosis.

PMID- 29470642
TI  - Real-World Switching to Riociguat: Management and Practicalities in Patients with
      PAH and CTEPH.
AB  - PURPOSE: A proportion of patients with pulmonary arterial hypertension (PAH) and
      chronic thromboembolic pulmonary hypertension (CTEPH) do not achieve treatment
      goals or experience side effects on their current therapy. In such cases,
      switching patients to a new drug while discontinuing the first may be a viable
      and appropriate treatment option. CAPTURE was designed to investigate how
      physicians manage the switching of patients to riociguat in real-world clinical
      practice. Observations from the study were used to assess whether recommendations
      in the riociguat prescribing information are reflected in clinical practice.
      METHODS: CAPTURE was an international, multicenter, uncontrolled, retrospective
      chart review that collected data from patients with PAH or inoperable or
      persistent/recurrent CTEPH who switched to riociguat from another pulmonary
      hypertension (PH)-targeted medical therapy. The primary objective of the study
      was to understand the procedure undertaken in real-world clinical practice for
      patients switching to riociguat. RESULTS: Of 127 patients screened, 125 were
      enrolled in CAPTURE. The majority of patients switched from a phosphodiesterase
      type 5 inhibitor (PDE5i) to riociguat and the most common reason for switching
      was lack of efficacy. Physicians were already using the recommended treatment
      free period when switching patients to riociguat from sildenafil, but a slightly
      longer period than recommended for tadalafil. In line with the contraindication,
      the majority of patients did not receive riociguat and PDE5i therapy
      concomitantly. Physicians also followed the recommended dose-adjustment procedure
      for riociguat. CONCLUSION: Switching to riociguat from another PH-targeted
      therapy may be feasible in real-world clinical practice in the context of the
      current recommendations.

PMID- 29470643
TI  - Diurnal, semidiurnal, and fortnightly tidal components in orthotidal proglacial
      rivers.
AB  - The orthotidal rivers are a new concept referring to inland rivers influenced by
      gravitational tides through the groundwater tides. "Orthotidal signals" is
      intended to describe tidal signals found in inland streamwaters (with no oceanic
      input); these tidal signals were locally generated and then exported into
      streamwaters. Here, we show that orthotidal signals can be found in proglacial
      rivers due to the gravitational tides affecting the glaciers and their
      surrounding areas. The gravitational tides act on glacier through earth and
      atmospheric tides, while the subglacial water is affected in a manner similar to
      the groundwater tides. We used the wavelet analysis in order to find tidally
      affected streamwaters. T_TIDE analyses were performed for discovering the tidal
      constituents. Tidal components with 0.95 confidence level are as follows: O1,
      PI1, P1, S1, K1, PSI1, M2, T2, S2, K2, and MSf. The amplitude of the diurnal
      tidal constituents is strongly influenced by the daily thermal cycle. The average
      amplitude of the semidiurnal tidal constituents is less altered and ranges from
      0.0007 to 0.0969 m. The lunisolar synodic fortnightly oscillation, found in the
      time series of the studied river gauges, is a useful signal for detecting
      orthotidal rivers when using noisier data. The knowledge of the orthotidal
      oscillations is useful for modeling fine resolution changes in rivers.

PMID- 29470644
TI  - Two genes encoding GH10 xylanases are essential for the virulence of the oomycete
      plant pathogen Phytophthora parasitica.
AB  - Plant cell walls are pivotal battlegrounds between microbial pathogens and their
      hosts. To penetrate the cell wall and thereby to facilitate infection, microbial
      pathogens are equipped with a wide array of cell wall-degrading enzymes to
      depolymerize the polysaccharides in the cell wall. However, many of these enzymes
      and their role in the pathogenesis of microbial pathogens are not characterized,
      especially those from Oomycetes. In this study, we analyzed the function of four
      putative endo-beta-1,4-xylanase-encoding genes (ppxyn1-ppxyn4) from Phytophthora
      parasitica, an oomycete plant pathogen known to cause severe disease in a wide
      variety of plant species. All four genes belong to the glycoside hydrolase family
      10 (GH10). Recombinant proteins of ppxyn1, ppxyn2, and ppxyn4 obtained from the
      yeast Pichia pastoris showed degrading activities toward birch wood xylan, but
      they behaved differently in terms of the conditions for optimal activity,
      thermostability, and durability. Quantitative RT-PCR revealed upregulated
      expression of all four genes, especially ppxyn1 and ppxyn2, during plant
      infection. In contrast, ppxyn3 was highly expressed in cysts and its close
      homolog, ppxyn4, in germinating cysts. To uncover the role of ppxyn1 and ppxyn2
      in the pathogenesis of P. parasitica, we generated silencing transformants for
      these two genes by double-stranded RNA-mediated gene silencing. Silencing ppxyn1
      and ppxyn2 reduced the virulence of P. parasitica toward tobacco (Nicotiana
      benthamiana) and tomato plants. These results demonstrate the crucial role of
      xylanase-encoding ppxyn1 and ppxyn2 in the infection process of P. parasitica.

PMID- 29470645
TI  - Branching the Tel2 pathway for exact fit on phosphatidylinositol 3-kinase-related
      kinases.
AB  - Phosphatidylinositol 3-kinase-related kinases (PIKKs), are structurally related
      to phosphatidylinositol 3-kinase (lipid kinase), but possess protein kinase
      activities. PIKKs include ATM, ATR, DNA-PK, mTOR and SMG1, key regulators of cell
      proliferation and genome maintenance. TRRAP, which is devoid of protein kinase
      activity, is the sixth member of the PIKK family. PIKK family members are
      gigantic proteins in the range of 300-500 kDa. It has become apparent in the last
      decade that the stability or maturation of the PIKK family members depends on a
      molecular chaperone called the Tel2-Tti1-Tti2 (TTT) complex. Several lines of
      evidence have established a model in which TTT connects to the Hsp90 chaperone
      through the Rvb1-Rvb2-Tah1-Pih1 (R2TP) complex in mammalian and yeast cells.
      However, recent studies of yeast cells indicate that TTT is able to form
      different complexes. These observations raise a possibility that several
      different mechanisms regulate TTT-mediated protein stability of PIKKs.

PMID- 29470646
TI  - Reactive oxygen radicals and gaseous transmitters in carotid body activation by
      intermittent hypoxia.
AB  - Sleep apnea is a prevalent respiratory disease characterized by periodic
      cessation of breathing during sleep causing intermittent hypoxia (IH). Sleep
      apnea patients and rodents exposed to IH exhibit elevated sympathetic nerve
      activity and hypertension. A heightened carotid body (CB) chemoreflex has been
      implicated in causing autonomic abnormalities in IH-treated rodents and in sleep
      apnea patients. The purpose of this article is to review the emerging evidence
      showing that interactions between reactive oxygen species (ROS) and gaseous
      transmitters as a mechanism cause hyperactive CB by IH. Rodents treated with IH
      exhibit markedly elevated ROS in the CB, which is due to transcriptional
      upregulation of pro-oxidant enzymes by hypoxia-inducible factor (HIF)-1 and
      insufficient transcriptional regulation of anti-oxidant enzymes by HIF-2. ROS, in
      turn, increases cystathionine gamma-lyase (CSE)-dependent H2S production in the
      CB. Blockade of H2S synthesis prevents IH-evoked CB activation. However, the
      effects of ROS on H2S production are not due to direct effects on CSE enzyme
      activity but rather due to inactivation of heme oxygenase-2 (HO-2), a carbon
      monoxide (CO) producing enzyme. CO inhibits H2S production through inactivation
      of CSE by PKG-dependent phosphorylation. During IH, reduced CO production
      resulting from inactivation of HO-2 by ROS releases the inhibition of CO on CSE
      thereby increasing H2S. Inhibiting H2S synthesis prevented IH-evoked sympathetic
      activation and hypertension.

PMID- 29470647
TI  - Dopaminergic innervation and modulation of hippocampal networks.
AB  - The catecholamine dopamine plays an important role in hippocampus-dependent
      plasticity and related learning and memory processes. Dopamine secretion in the
      hippocampus is activated by, e.g., salient or novel stimuli, thereby helping to
      establish and to stabilize hippocampus-dependent memories. Disturbed dopaminergic
      function in the hippocampus leads to severe pathophysiological conditions. While
      the role and importance of dopaminergic modulation of hippocampal networks have
      been unequivocally proven, there is still a lack of detailed molecular and
      cellular mechanistic understanding of how dopamine orchestrates these hippocampal
      processes. In this chapter of the special issue "Hippocampal structure and
      function," we will discuss the current understanding of dopaminergic modulation
      of basal synaptic transmission and long-lasting, activity-dependent potentiation
      or depression.

PMID- 29470648
TI  - Reply to letter to editor regarding: LHRH analog therapy is associated with worse
      metabolic side effects than bilateral orchiectomy in prostate cancer.

PMID- 29470649
TI  - Structural arrangement of the intrinsic muscles of the tongue and their
      relationships with the extrinsic muscles.
AB  - The tongue is a dense muscular organ, in which the muscles are arranged in a
      confusing pattern. The intrinsic muscles were gross anatomically investigated in
      25 cadavers to clarify their configuration. The superior longitudinal muscle
      (SLm) ran beneath the dorsal mucosa and was divided into bundles by the other
      muscles passing through it to the dorsum. The external bundle of the
      styloglossus, with the palatoglossus, coursed externally to the hyoglossus. Their
      fibers spread beneath the SLm or attached to the apex and the inferior
      longitudinal muscle (ILm) ascended from the root and joined them. The
      genioglossus and the anterior part of the hyoglossus extended internally and
      externally to the ILm, respectively, to the dorsum, and the vertical muscle was
      sandwiched between them. The transverse muscle passed laterally from the lingual
      septum. The fibers of the posterior part of the hyoglossus converged to the root
      and spread beneath the SLm. The intersections between these vertical and
      transverse fibers divided one another into bundles or lamellae. The middle bundle
      of the styloglossus, passing between the two parts of the hyoglossus, was divided
      into slips by the intersection with the genioglossus. The internal bundle of the
      styloglossus, with the glossopharyngeus, descended internally to the posterior
      part to the root. The findings indicate that the intrinsic and extrinsic muscles
      of the tongue are not independent groups, and their fibers form a three
      dimensional latticework. Each muscle contains numerous bundles or lamellae as
      functional units that can act separately or cooperate across the muscles.

PMID- 29470651
TI  - Prediction of surgical site infection in spine surgery from tests of nasal MRSA
      colonization and drain tip culture.
AB  - PURPOSE: MRSA is an organism that is a possible risk factor for postoperative
      SSI. The purpose of the study was to examine relationships among surgical site
      infection (SSI) after spinal surgery, nasal methicillin-resistant staphylococcus
      aureus (MRSA) colonization, and wound drain culture results. METHODS: The
      subjects were 132 patients who underwent spinal instrumentation surgery. A
      preoperative nasal swab was used to check for the presence of MRSA colonization,
      and a wound drain tip culture was performed for detection of SSI. Data from
      culture studies using nasal samples and those from the distal tip of the wound
      drain were used for analysis. RESULTS: Five patients (3.8%) had nasal MRSA, 17
      (13%) had positive drain tip cultures, 15 (11%) had SSIs, and 10 (8%) had SSIs
      with MRSA. Patients with nasal MRSA had a higher rate of detection of bacteria in
      the drain tip culture (40 vs. 19%, p = 0.065), and the SSI rate was significantly
      higher in patients with a positive drain tip culture (33 vs. 10%, p = 0.012). The
      total SSI rate differed significantly between patients with and without nasal
      MRSA (40 vs. 10%, p = 0.039); however, the SSI with MRSA rate did not differ
      significantly between these groups. CONCLUSION: MRSA carriers were not
      necessarily associated with MRSA infection, but were related to a positive drain
      tip culture and SSI, which might be due to endogenous skin bacteria. Therefore,
      possible SSI should be considered in patients with nasal MRSA colonization or
      bacteria detected in a drain tip culture.

PMID- 29470650
TI  - Management of knee dislocation prior to ligament reconstruction: What is the
      current evidence? Update of a universal treatment algorithm.
AB  - Traumatic knee dislocation is a rare but potentially limb-threatening injury.
      Thus proper initial diagnosis and treatment up to final ligament reconstruction
      are extremely important and a precondition to successful outcomes. Reports
      suggest that evidence-based systematic approaches lead to better results. Because
      of the complexity of this injury and the inhomogeneity of related literature,
      there are still various controversies and knowledge gaps regarding decision
      making and step-sequencing in the treatment of acute multi-ligament knee injuries
      and knee dislocations. The use of ankle-brachial index, routine or selective
      angiography, braces, joint-spanning or dynamic external fixation, and the
      necessity of initial ligament re-fixation during acute surgery constitutes
      current topics of a scholarly debate. The aim of this article was to provide a
      comprehensive literature review bringing light into some important aspects about
      the initial treatment of knee dislocation (vascular injury, neural injury,
      immobilization techniques) and finally develop an accurate data-based universal
      algorithm, enabling attending physicians to become more acquainted with the
      management of acute knee dislocation.

PMID- 29470652
TI  - Engineering of chitosan and collagen macromolecules using sebacic acid for
      clinical applications.
AB  - Transformation of natural polymers to three-dimensional (3D) scaffolds for
      biomedical applications faces a number of challenges, viz., solubility, stability
      (mechanical and thermal), strength, biocompatibility, and biodegradability.
      Hence, intensive research on suitable agents to provide the requisite properties
      has been initiated at the global level. In the present study, an attempt was made
      to engineer chitosan and collagen macromolecules using sebacic acid, and further
      evaluation of the mechanical stability and biocompatible property of the
      engineered scaffold material was done. A 3D scaffold material was prepared using
      chitosan at 1.0% (w/v) and sebacic acid at 0.2% (w/v); similarly, collagen at
      0.5% (w/v) and sebacic acid at 0.2% (w/v) were prepared individually by freeze
      drying technique. Analysis revealed that the engineered scaffolds displayed an
      appreciable mechanical strength and, in addition, were found to be biocompatible
      to NIH 3T3 fibroblast cells. Studies on the chemistry behind the interaction and
      the characteristics of the cross-linked scaffold materials suggested that non
      covalent interactions play a major role in deciding the property of the said
      polymer materials. The prepared scaffold was suitable for tissue engineering
      application as a wound dressing material.

PMID- 29470653
TI  - [Lymph-node-positive penile cancer : Management and systemic therapy].
AB  - Cancer-specific survival in men with penile cancer depends foremost on regional
      lymphatic metastasis and its extent. Patients with limited inguinal lymph node
      metastases have a 5-year survival of up to 80%. However, those with pelvic lymph
      node metastases and/or systemic disease have a 5-year survival prognosis of only
      0-33%. In any case, in patients with regional lymph node metastases multimodal
      treatment with complete lymphadenectomy and adjuvant chemotherapy is indicated.

PMID- 29470654
TI  - [Molecular characterization of penile cancer : Literature review of new
      prognostic markers and potential therapeutic targets].
AB  - Squamous cell carcinoma of the penis (SCCP) is a rare cancer type in Western
      industrialized nations; nevertheless, it shows an aggressive course of disease in
      advanced tumor stages with accordantly high recurrence and progression rates.
      While molecular biomarkers are not established in clinical routine for the
      management of SCCP patients yet, the accordant unmet need is enormous, as
      adequate biomarkers would be meaningful for prognostic determination, planning of
      modality and extent of primary therapy, indication for inguinal lymph node
      resection, adjuvant treatment, and as potential targets for specific systemic
      treatment. SCCP regularly develops from a precursor lesion. In this regard, human
      papillomavirus (HPV)-dependent and -independent pathways are differentiated. The
      potential for specific target therapy options is mainly based on the decoding of
      genetic and epigenetic signatures of distinct molecular pathways. In order to
      develop targeted and personalized treatment strategies based on molecular
      pathways, an increase in translational research in large multi-institutional
      collaborations must be promoted. This review article aims to summarize the
      current status of research concerning molecular changes related to SCCP under
      separate consideration of prognostic molecular markers, on the one hand, and
      biomarkers considered potential therapeutic targets, on the other hand. In
      addition, previous research activities of our own working group on this topic are
      briefly described.

PMID- 29470655
TI  - [Lymph node management of cN0 penile cancer].
AB  - In penile cancer, lymph node metastasis is the main known prognostic factor
      affecting patients' survival. Early inguinal lymph node dissection or the
      resection of clinically occult lymph node metastases improves survival compared
      with removal when the metastases become clinically apparent. Micrometastatic
      lymph node involvement is undetectable by current imaging modalities. Nomograms
      based on clinical and histopathological tumor characteristics are unreliable in
      predicting lymph node involvement. Consequently, in penile cancer patients with
      clinically normal inguinal lymph nodes (cN0) and a tumor stage >=pT1, G2 surgical
      lymph node exploration is recommended. Radical inguinal lymphadenectomy is no
      longer recommended because of its invasiveness and high complication rate.
      Modified lymphadenectomy and dynamic sentinel lymph node surgery allow the
      detection of lymph node-positive patients with sufficient certainty. Thereby, the
      sentinel lymph node approach offers the least invasiveness and high sensitivity.
      Extended inguinal lymphadenectomy is still recommended in the case of positive
      nodes.

PMID- 29470656
TI  - Industrial point source CO2 emission strength estimation with aircraft
      measurements and dispersion modelling.
AB  - CO2 remains the greenhouse gas that contributes most to anthropogenic global
      warming, and the evaluation of its emissions is of major interest to both
      research and regulatory purposes. Emission inventories generally provide quite
      reliable estimates of CO2 emissions. However, because of intrinsic uncertainties
      associated with these estimates, it is of great importance to validate emission
      inventories against independent estimates. This paper describes an integrated
      approach combining aircraft measurements and a puff dispersion modelling
      framework by considering a CO2 industrial point source, located in Biganos,
      France. CO2 density measurements were obtained by applying the mass balance
      method, while CO2 emission estimates were derived by implementing the
      CALMET/CALPUFF model chain. For the latter, three meteorological initializations
      were used: (i) WRF-modelled outputs initialized by ECMWF reanalyses; (ii) WRF
      modelled outputs initialized by CFSR reanalyses and (iii) local in situ
      observations. Governmental inventorial data were used as reference for all
      applications. The strengths and weaknesses of the different approaches and how
      they affect emission estimation uncertainty were investigated. The mass balance
      based on aircraft measurements was quite succesful in capturing the point source
      emission strength (at worst with a 16% bias), while the accuracy of the
      dispersion modelling, markedly when using ECMWF initialization through the WRF
      model, was only slightly lower (estimation with an 18% bias). The analysis will
      help in highlighting some methodological best practices that can be used as
      guidelines for future experiments.

PMID- 29470657
TI  - Characterization of crystalline cellulose of jute reinforced poly (vinyl alcohol)
      (PVA) biocomposite film for potential biomedical applications.
AB  - Cellulose crystals (CC) were chemically derived from jute by alkali treatment,
      bleaching and subsequent hydrolysis with 40 % sulfuric acid. Infrared
      spectroscopy (FT-IR) suggested sufficient removal of lignin and hemicellulose
      from the raw jute and scanning electron microscopy (SEM), and X-ray diffraction
      (XRD) studies demonstrated the preparation of microcrystalline cellulose. CC
      reinforced polyvinyl alcohol (PVA) composite was prepared by solution casting
      method under laminar flow. In order to maintain uniform dispersion of 3-15 %
      (w/w) of the CC in the composite N, N dimethylformamide (DMF) was used as a
      dispersant. FT-IR, XRD, SEM, thermogravimetric analysis (TG, DTG and DTA) and
      thermomechanical analyses (TMA) were used to characterize the CC and the
      composites. The study of tensile properties showed that tensile strength (TS) and
      modulus (TM) increase with increasing CC content up to 9 % and then decrease with
      the addition of a high content of CC (above 9 %) because of the aggregation of
      CCs in the composite. The highest TS (43.9 MPa) and TM (2,190 MPa) have been
      shown to be the composite prepared with 9 % CC and the lowest to be from pure PVA
      film 17.1 and 1470 MPa. In addition, the composites have showed no cytotoxicity
      that can also prohibit microbial growth and; hence, it can be a potential
      material for biomedical applications such as wound healing accelerators.

PMID- 29470658
TI  - Current Status of Potential Therapies for IgE-Mediated Food Allergy.
AB  - PURPOSE OF REVIEW: The goal of this review is to provide the reader with an
      updated summary of published trial data regarding the use of oral immunotherapy
      (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) for
      treatment of IgE-mediated food allergies. RECENT FINDINGS: Data from phase 2
      trials for treatment of peanut allergy with OIT and EPIT reveal an increase in
      the threshold of reactivity for peanut-allergic children. Compared to EPIT, OIT
      promotes a greater increase in the threshold of reactivity; however, adverse
      events are more common with OIT. OIT, EPIT, and SLIT appear to modulate the
      immune response for some food-allergic individuals. Data regarding utility for
      treatment of food allergies regardless of modality is limited to few foods, as is
      investigation into treatment of food-allergic infants, young children, and
      adults. Future trials are likely to focus on young children, food allergies other
      than peanut, and treatment of multifood-allergic individuals.

PMID- 29470659
TI  - Impact of Particulate Air Pollution on Cardiovascular Health.
AB  - PURPOSE OF REVIEW: Air pollution is established as an independent risk factor for
      cardiovascular diseases (CVDs). Ambient particulate matter (PM), a principal
      component of air pollutant, has been considered as a main culprit of the adverse
      effects of air pollution on human health. RECENT FINDINGS: Extensive
      epidemiological and toxicological studies have demonstrated particulate air
      pollution is positively associated with the development of CVDs. Short-term PM
      exposure can trigger acute cardiovascular events while long-term exposure over
      years augments cardiovascular risk to an even greater extent and can reduce life
      expectancy by a few years. Inhalation of PM affects heart rate variability, blood
      pressure, vascular tone, blood coagulability, and the progression of
      atherosclerosis. The potential molecular mechanisms of PM-caused CVDs include
      direct toxicity to the cardiovascular system or indirect injury by inducing
      systemic inflammation and oxidative stress in circulation. This review mainly
      focuses on the acute and chronic effects of ambient PM exposure on the
      development of cardiovascular diseases and the possible mechanisms for PM-induced
      increases in cardiovascular morbidity and mortality. Additionally, we summarized
      some appropriate interventions to attenuate PM air pollution-induced
      cardiovascular adverse effects, which may promote great benefits to public
      health.

PMID- 29470660
TI  - The Effect of Inhalant Organic Dust on Bone Health.
AB  - PURPOSE OF REVIEW: Agriculture remains a major economic sector globally, and
      workers experience high rates of chronic inflammatory lung and musculoskeletal
      diseases. Whereas obstructive pulmonary diseases are known risk factors for bone
      loss, the underlying relationship between lung inflammation and bone health is
      not well known. RECENT FINDINGS: An agriculture organic dust extract inhalation
      animal model has recently linked lung injury-induced inflammation to systemic
      bone loss. This process is dependent upon lipopolysaccharide and the toll-like
      receptor 4 (TLR4) signaling pathway. Downstream systemic interleukin-6 is a key
      mediator that subsequently activates osteoclastogenesis. Age is a host factor
      that impacted bone disease with younger mice demonstrating increased
      susceptibility to bone loss following inhalant exposures as compared to older
      mice. Supplemental dietary vitamin D was shown to prevent organic dust-induced
      bone loss, but not lung disease, in animals. Recent animal studies provide new
      mechanistic insight into the lung-bone inflammatory axis. Host factors, diet, and
      lipopolysaccharide/TLR4 signaling pathways play a significant role in explaining
      how inhalant organic dust exposures impact bone health. These investigations
      might lead to specific targeted therapeutic approaches.

PMID- 29470661
TI  - Granulomatous-Lymphocytic Interstitial Lung Disease in 22q11.2 Deletion Syndrome:
      a Case Report and Literature Review.
AB  - PURPOSE OF REVIEW: Granulomatous-lymphocytic interstitial lung disease (GLILD)
      has classically been associated with common variable immune deficiency (CVID),
      but is increasingly being reported in other immunodeficiencies. We describe the
      second reported case of GLILD in a patient with 22q11.2 deletion syndrome
      (22q11.2DS) and review the recent literature surrounding GLILD. RECENT FINDINGS:
      GLILD is characterized by granulomata and lymphoproliferation. Consensus
      statements and retrospective and case-control studies have better elucidated the
      clinicopathological and radiographic manifestations of GLILD, allowing for its
      differentiation from similar conditions like sarcoidosis. Gaps of knowledge
      remain, however, particularly regarding optimal management strategies.
      Combination therapies targeting T and B cell populations have recently shown
      favorable results. GLILD is associated with poorer outcomes in CVID. Its
      recognition as a rare complication of 22q11.2DS and other immunodeficiencies
      therefore has important therapeutic and prognostic implications. Additional
      research is needed to better understand the natural history and pathogenesis of
      GLILD and to develop evidence-based practice guidelines.

PMID- 29470662
TI  - Current status of water environment and their microbial biosensor techniques -
      Part I: Current data of water environment and recent studies on water quality
      investigations in Japan, and new possibility of microbial biosensor techniques.
AB  - In my 2010 review, I addressed conventional water analysis and biosensing of
      organic pollutants in Japan between 1960s and 2000s. It is now timely to
      reexamine current analytical and biomonitoring approaches in view of the new
      challenges in assessing pollution, particularly in closed water bodies, as
      pollutants tend to accumulate in these endorheic basins. In the present review
      series, I presented current water environment and its microbial biosensors. In
      this part, I presented current data of the water quality of these water bodies in
      Japan and established the need to further develop microbial biosensor
      technologies to address and monitor water quality here. Graphical Abstract
      Current water pollution indirectly occurring by anthropogenic eutrophication
      (Part I).

PMID- 29470663
TI  - Miniaturized dispersive liquid-liquid microextraction and MALDI MS using ionic
      liquid matrices for the detection of bacterial communication molecules and
      virulence factors.
AB  - The identification and quantification of molecules involved in bacterial
      communication are major prerequisites for the understanding of interspecies
      interactions at the molecular level. We developed a procedure allowing the
      determination of 2-heptyl-4(1H)-quinolone (HHQ) and 2-heptyl-3-hydroxy-4(1H)
      quinolone (PQS) and the virulence factor pyocyanin (PYO) formed by the Gram
      negative bacterium Pseudomonas aeruginosa. The method is based on dispersive
      liquid-liquid microextraction from small supernatant volumes (below 10 MUL)
      followed by quantitative matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry (MS). The use of ionic liquid matrix led to a lowered limit of
      detection for pyocyanin and, due to suppression of matrix background signals,
      easy to interpret mass spectra compared to crystalline matrices. Using an isotope
      labeled pyocyanin standard synthesized in small-scale synthesis, quantitative
      analysis spanning approximately one order of magnitude (0.5 to 250 fmol) was
      feasible. The method was successfully applied to the detection of the signaling
      molecules PQS and HHQ in cultures of P. aeruginosa strains isolated from sputum
      of cystic fibrosis patients and allowed a highly sensitive quantification of PYO
      from these cultures. Hence, the developed method bears the potential to be used
      for screening purposes in clinical settings and will help to decipher the
      molecular basis of bacterial communication. Graphical abstract Ionic liquid
      matrices for the detection and quantification of the toxin pyocyanin and other
      signaling molecules from P. aeruginosa by MALDI MS.

PMID- 29470664
TI  - Toward miniaturized analysis of chemical identity and purity of
      radiopharmaceuticals via microchip electrophoresis.
AB  - Miniaturized synthesis of positron emission tomography (PET) tracers is poised to
      offer numerous advantages including reduced tracer production costs and increased
      availability of diverse tracers. While many steps of the tracer production
      process have been miniaturized, there has been relatively little development of
      microscale systems for the quality control (QC) testing process that is required
      by regulatory agencies to ensure purity, identity, and biological safety of the
      radiotracer before use in human subjects. Every batch must be tested, and in
      contrast with ordinary pharmaceuticals, the whole set of tests of
      radiopharmaceuticals must be completed within a short-period of time to minimize
      losses due to radioactive decay. By replacing conventional techniques with
      microscale analytical ones, it may be possible to significantly reduce instrument
      cost, conserve lab space, shorten analysis times, and streamline this aspect of
      PET tracer production. We focus in this work on miniaturizing the subset of QC
      tests for chemical identity and purity. These tests generally require high
      resolution chromatographic separation prior to detection to enable the approach
      to be applied to many different tracers (and their impurities), and have not yet,
      to the best of our knowledge, been tackled in microfluidic systems. Toward this
      end, we previously explored the feasibility of using the technique of capillary
      electrophoresis (CE) as a replacement for the "gold standard" approach of using
      high-performance liquid chromatography (HPLC) since CE offers similar separating
      power, flexibility, and sensitivity, but can readily be implemented in a
      microchip format. Using a conventional CE system, we previously demonstrated the
      successful separation of non-radioactive version of a clinical PET tracer, 3'
      deoxy-3'-fluorothymidine (FLT), from its known by-products, and the separation of
      the PET tracer 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-cytosine (D-FAC)
      from its alpha-isomer, with sensitivity nearly as good as HPLC. Building on this
      feasibility study, in this paper, we describe the first effort to miniaturize the
      chemical identity and purity tests by using microchip electrophoresis (MCE). The
      fully automated proof-of-concept system comprises a chip for sample injection, a
      separation capillary, and an optical detection chip. Using the same model
      compound (FLT and its known by-products), we demonstrate that samples can be
      injected, separated, and detected, and show the potential to match the
      performance of HPLC. Addition of a radiation detector in the future would enable
      analysis of radiochemical identity and purity in the same device. We envision
      that eventually this MCE method could be combined with other miniaturized QC
      tests into a compact integrated system for automated routine QC testing of
      radiopharmaceuticals in the future. Graphical abstract Miniaturized quality
      control (QC) testing of batches of radiopharmaceuticals via microfluidic
      analysis. The proof-of-concept hybrid microchip electrophoresis (MCE) device
      demonstrated the feasibility of achieving comparable performance to conventional
      analytical instruments (HPLC or CE) for chemical purity testing.

PMID- 29470665
TI  - A new method for water quality assessment: by harmony degree equation.
AB  - Water quality assessment is an important basic work in the development,
      utilization, management, and protection of water resources, and also a
      prerequisite for water safety. In this paper, the harmony degree equation (HDE)
      was introduced into the research of water quality assessment, and a new method
      for water quality assessment was proposed according to the HDE: by harmony degree
      equation (WQA-HDE). First of all, the calculation steps and ideas of this method
      were described in detail, and then, this method with some other important methods
      of water quality assessment (single factor assessment method, mean-type
      comprehensive index assessment method, and multi-level gray correlation
      assessment method) were used to assess the water quality of the Shaying River
      (the largest tributary of the Huaihe in China). For this purpose, 2 years (2013
      2014) dataset of nine water quality variables covering seven monitoring sites,
      and approximately 189 observations were used to compare and analyze the
      characteristics and advantages of the new method. The results showed that the
      calculation steps of WQA-HDE are similar to the comprehensive assessment method,
      and WQA-HDE is more operational comparing with the results of other water quality
      assessment methods. In addition, this new method shows good flexibility by
      setting the judgment criteria value HD0 of water quality; when HD0 = 0.8, the
      results are closer to reality, and more realistic and reliable. Particularly,
      when HD0 = 1, the results of WQA-HDE are consistent with the single factor
      assessment method, both methods are subject to the most stringent "one vote veto"
      judgment condition. So, WQA-HDE is a composite method that combines the single
      factor assessment and comprehensive assessment. This research not only broadens
      the research field of theoretical method system of harmony theory but also
      promotes the unity of water quality assessment method and can be used for
      reference in other comprehensive assessment.

PMID- 29470666
TI  - The effect of polymer and CaCl2 concentrations on the sulfasalazine release from
      alginate-N,O-carboxymethyl chitosan beads.
AB  - In this study, pH-sensitive blended polymeric beads were prepared by ionic
      gelation of mixed alginate and N,O-carboxymethyl chitosan (NOCC) solutions in
      aqueous media containing calcium chloride. To prepare drug-loaded beads,
      sulfasalazine (SA) as a model drug was added to the initial aqueous polymer
      solution. These beads were characterized and evaluated in vitro as potential
      carriers for colon-specific drug delivery. A 32 full factorial experimental
      design was employed to evaluate the effect of polymer and CaCl2 concentrations on
      swelling and drug release behavior of the beads in simulated gastrointestinal
      tract fluid. It was found that the rate of swelling and drug release decreased
      significantly with increasing polymer and CaCl2 concentrations, but polymer
      concentration was more effective than CaCl2 concentration. The beads prepared
      using 4.5% polymer concentration and 4% CaCl2 concentration retained
      approximately 60% of the loaded drug before approaching the simulated colonic
      fluid. Based on the results, the alginate-NOCC beads prepared with high polymer
      concentration could be potentially suitable polymeric carriers for colon-specific
      delivery of SA.

PMID- 29470667
TI  - Microhardness of bi-antibiotic-eluting bone cement scaffolds.
AB  - Bi-antibiotic-impregnated bone cements (BIBCs) are widely used in orthopaedics as
      a prophylactic agent (depot) to address post-surgical infections. Although
      hardness is widely considered a viable index to measure the integrity of the
      cement structure, there are few specific studies involving changes in hardness
      characteristics of BIBCs post elution of high doses of two widely used
      antibiotics: tobramycin and gentamicin. Increased doses of antibiotics and
      increased duration of elution may also decrease the hardness of polymethyl
      methacrylate (PMMA) bone cement, thus increasing the chances of shattering,
      scratching, and deformation.In this project, we have investigated the changes in
      surface hardness of five different antibiotic-loaded specimens: 0.5 g tobramycin
      and 0.5 g gentamicin together, 1 g tobramycin, 1 g gentamicin, 5 g tobramycin and
      5 g gentamicin together, and 10 g tobramycin (each added to 40 g of PMMA), post
      elution for various time periods (1, 3, and 21 days). The effect of hydration on
      the hardness of bone cement was studied to replicate in vivo conditions. The
      micro-indentation tester (Buehler m5103) was utilized to determine if the
      increased antibiotic loads would compromise the integrity of the bone cement
      matrix.The results demonstrated that the amount of drug initially incorporated
      determined the hardness of the cement post elution. As compared to the control
      (no antibiotic), specimens containing 1 and 10 g of antibiotic exhibited over 50%
      and 73% decrease in hardness, respectively. The different treatment durations
      (post 1 day) as well as the hydration conditions had insignificant effect on the
      hardness of the cement.

PMID- 29470668
TI  - Indoor Environmental Interventions and their Effect on Asthma Outcomes.
AB  - PURPOSE OF REVIEW: The use of environmental interventions to improve outcomes in
      asthmatics has long been an elusive goal. While numerous interventions have been
      studied, the results of clinical trials have been mixed. This review aims to
      identify combinations of interventions that have been proven to be effective and
      to propose a model for using them in a clinical setting. RECENT FINDINGS: An NIH
      workshop emphasized a need for research to identify effective interventions for
      reducing indoor exposures and improving asthma outcomes. A number of innovative
      measures were described, though evidence supporting their use was lacking. A
      recent systematic review described various interventions for which evidence is
      available. The greatest challenge for this approach is the same as that for the
      medical approach to treatment: nonadherence. Given evidence for effective
      interventions, control of environmental exposures should lead to improved asthma
      outcomes. Methods to improve adherence need to be identified.

PMID- 29470669
TI  - Electrospun poly(caprolactone)-elastin scaffolds for peripheral nerve
      regeneration.
AB  - Peripheral nerve regeneration can be enhanced by chemical and mechanical cues for
      neurite growth. Aligned and randomly oriented electrospun nanofibers of
      poly(epsilon-caprolactone) (PCL) or a blend of PCL and elastin were fabricated to
      test their potential to provide contact guidance to embryonic chick dorsal root
      ganglia for peripheral nerve regeneration. Scanning electron microscopy was used
      to analyze the fiber diameter. Fiber diameter was found to be significantly
      smaller when elastin was incorporated into the scaffold (934 +/- 58 nm for PCL
      and 519 +/- 36 nm for PCL:elastin). After 24 h in culture, there was preferential
      cell attachment and neurite extension along the fibers of the elastin-containing
      scaffolds (average neurite extension 173.4 +/- 20.7 MUm), indicating that the
      presence of elastin promotes neurite outgrowth on electrospun scaffolds.

PMID- 29470671
TI  - Predicting soil water content at - 33 kPa by pedotransfer functions in stoniness
      1 soils in northeast Venezuela.
AB  - Soil water content is a key property in the study of water available for plants,
      infiltration, drainage, hydraulic conductivity, irrigation, plant water stress
      and solute movement. However, its measurement consumes time and, in the case of
      stony soils, the presence of stones difficult to determinate the water content.
      An alternative is the use of pedotransfer functions (PTFs), as models to predict
      these properties from readily available data. The present work shows a comparison
      of different widely used PTFs to estimate water content at-33 kPa (WR-33kPa) in
      high stoniness soils. The work was carried out in the Caramacate River, an area
      of high interest because the frequent landslides worsen the quality of drinking
      water. The performance of all evaluated PTFs was compared with a PTF generated
      for the study area. Results showed that the Urach's PTF presented the best
      performance in relation to the others and could be used to estimate WR-33kPa in
      soils of Caramacate River basin. The calculated PTFs had a R2 of 0.65. This was
      slightly higher than the R2 of the Urach's PTF. The inclusion of the rock
      fragment volume could have the better results. The weak performance of the other
      PTFs could be related to the fact that the mountain soils of the basin are rich
      in 2:1 clay and high stoniness, which were not used as independent variables for
      PTFs to estimate the WR-33kPa.

PMID- 29470672
TI  - Infrared spectroscopic analysis of restorative composite materials' surfaces and
      their saline extracts.
AB  - This study aims at finding out if multiple attenuated internal reflection
      infrared (MAIR-IR) spectroscopic analysis can be used as a tool to differentiate
      commercial resin composite brands and to find out if different resin composites
      will have different abilities of leaching materials that are cytotoxic to human
      gingival fibroblasts (HGFs) Tooth-colored resin fillings have become increasingly
      popular as restorative materials, which make it important to differentiate the
      commercial brands for forensic and biological purposes. Fourteen resin composite
      brands were used in the study. MAIR-IR spectroscopic analysis was used for
      surface characterization of the organic and inorganic parts of the resin
      composite samples which were studied as is and after 2 weeks of saline
      incubation. IR spectroscopy was also done on the saline extracts to find out if
      different resin composite materials would have different leaching abilities. The
      saline extracts were also used for the viability testing of HGF cell cultures.
      One-way analysis of variance test statistics was used to analyze the results. It
      was found that the resin composite brands have different spectra after saline
      soaking. It was also found that these resin composite brands possess different
      leaching abilities with regard to the amount and type of materials and different
      cytotoxic effects, which were found to be threshold dependent, meaning there is a
      critical or threshold value of leaching material at or above which the toxic
      effect will be significant and below which there is no toxic effect. Therefore,
      IR spectroscopy might be considered as a useful tool for dental resin composite
      characterization. However, more oral simulating environmental testing methods,
      different surface characterization methods, and more cell viability testing
      methods and assays must be considered for more specific results which relate more
      to the behavior of these dental resin composites in the oral environment.

PMID- 29470673
TI  - How much does the treatment of each major disease cost? A decomposition of Swiss
      National Health Accounts.
AB  - In most countries, surprisingly little is known on how national healthcare
      spending is distributed across diseases. Single-disease cost-of-illness studies
      cover only a few of the diseases affecting a population and in some cases lead to
      untenably large estimates. The objective of this study was to decompose
      healthcare spending in 2011, according to Swiss National Health Accounts, into 21
      collectively exhaustive and mutually exclusive major disease categories. Diseases
      were classified following the Global Burden of Disease Study. We first assigned
      the expenditures directly mapping from National Health Accounts to the 21
      diseases. The remaining expenditures were assigned based on diagnostic codes and
      clues contained in a variety of microdata sources. Expenditures were dominated by
      non-communicable diseases with a share of 79.4%. Cardiovascular diseases stood
      out with 15.6% of total spending, followed by musculoskeletal disorders (13.4%),
      and mental and substance use disorders (10.6%). Neoplasms (6.0% of the total)
      ranked only sixth, although they are the leading cause of premature death in
      Switzerland. These results may be useful for the design of health policies, as
      they illustrate how healthcare spending is influenced by the epidemiological
      transition and increasing life expectancy. They also provide a plausibility check
      for single cost-of-illness studies. Our study may serve as a starting point for
      further research on the drivers of the constant growth of healthcare spending.

PMID- 29470674
TI  - Evaluation of silk sericin as a biomaterial: in vitro growth of human corneal
      limbal epithelial cells on Bombyx mori sericin membranes.
AB  - Sericin and fibroin are the two major proteins in the silk fibre produced by the
      domesticated silkworm, Bombyx mori. Fibroin has been extensively investigated as
      a biomaterial. We have previously shown that fibroin can function successfully as
      a substratum for growing cells of the eye. Sericin has been so far neglected as a
      biomaterial because of suspected allergenic activity. However, this misconception
      has now been dispelled, and sericin's biocompatibility is currently indisputable.
      Aiming at promoting sericin as a possible substratum for the growth of corneal
      cells in order to make tissue-engineered constructs for the restoration of the
      ocular surface, in this study we investigated the attachment and growth in vitro
      of human corneal limbal epithelial cells (HLECs) on sericin-based membranes.
      Sericin was isolated and regenerated from the silkworm cocoons by an aqueous
      procedure, manufactured into membranes, and characterized (mechanical properties,
      structural analysis, contact angles). Primary cell cultures from two donors were
      established in serum-supplemented media in the presence of murine feeder cells.
      Membranes made of sericin and fibroin-sericin blends were assessed in vitro as
      substrata for HLECs in a serum-free medium, in a cell attachment assay and in a 3
      day cell growth experiment. While the mechanical characteristics of sericin were
      found to be inferior to those of fibroin, its ability to enhance the attachment
      of HLECs was significantly superior to fibroin, as revealed by the PicoGreen(r)
      assay. Evidence was also obtained that cells can grow and differentiate on these
      substrata.

PMID- 29470675
TI  - St. Catherine of Siena (1347-1380 AD): one of the earliest historic cases of
      altered gustatory perception in anorexia mirabilis.
AB  - St. Catherine of Siena suffered from an extreme form of holy fasting, a condition
      classified as anorexia mirabilis (also known as inedia prodigiosa). Historical
      and medical scholarships alike have drawn a comparison between this primaeval
      type of anorexia with a relatively common form of eating disorder among young
      women in the modern world, anorexia nervosa. St. Catherine's condition was
      characterised by a disgust for sweet taste, a condition also described in
      anorexia nervosa, and characterised by specific neurophysiological changes in the
      brain. St. Catherine's case may be considered one of the oldest veritable
      descriptions of altered gustation (dysgeusia). Moreover, a more compelling
      neurophysiological similarity between anorexia mirabilis and anorexia nervosa may
      be proposed.

PMID- 29470670
TI  - Calcium orthophosphate coatings, films and layers.
AB  - In surgical disciplines, where bones have to be repaired, augmented or improved,
      bone substitutes are essential. Therefore, an interest has dramatically increased
      in application of synthetic bone grafts. As various interactions among cells,
      surrounding tissues and implanted biomaterials always occur at the interfaces,
      the surface properties of the implants are of the paramount importance in
      determining both the biological response to implants and the material response to
      the physiological conditions. Hence, a surface engineering is aimed to modify
      both the biomaterials, themselves, and biological responses through introducing
      desirable changes to the surface properties of the implants but still maintaining
      their bulk mechanical properties. To fulfill these requirements, a special class
      of artificial bone grafts has been introduced in 1976. It is composed of various
      mechanically stable (therefore, suitable for load bearing applications)
      biomaterials and/or bio-devices with calcium orthophosphate coatings, films and
      layers on their surfaces to both improve interactions with the surrounding
      tissues and provide an adequate bonding to bones. Many production techniques of
      calcium orthophosphate coatings, films and layers have been already invented and
      new promising techniques are continuously investigated. These specialized
      coatings, films and layers used to improve the surface properties of various
      types of artificial implants are the topic of this review.

PMID- 29470676
TI  - Evaluation of polyphenylene ether ether sulfone/nanohydroxyapatite nanofiber
      composite as a biomaterial for hard tissue replacement.
AB  - The present work is aimed at investigating the mechanical and in vitro biological
      properties of polyphenylene ether ether sulfone (PPEES)/nanohydroxyapatite (nHA)
      composite fibers. Electrospinning was used to prepare nanofiber composite mats of
      PPEES/nHA with different weight percentages of the inorganic filler, nHA. The
      fabricated composites were characterized using Fourier transform infrared
      spectroscopy (FTIR)-attenuated total reflectance spectroscopy (ATR) and scanning
      electron microscopy (SEM)-energy dispersive X-ray spectroscopy (EDX) techniques.
      The mechanical properties of the composite were studied with a tensile tester.
      The FTIR-ATR spectrum depicted the functional group as well as the interaction
      between the PPEES and nHA composite materials; in addition, the elemental groups
      were identified with EDX analysis. The morphology of the nanofiber composite was
      studied by SEM. Tensile strength analysis of the PPEES/nHA composite revealed the
      elastic nature of the nanofiber composite reinforced with nHA and suggested
      significant mechanical strength of the composite. The biomineralization studies
      performed using simulated body fluid with increased incubation time showed
      enhanced mineralization, which showed that the composites possessed high
      bioactivity property. Cell viability of the nanofiber composite, studied with
      osteoblast (MG-63) cells, was observed to be higher in the composites containing
      higher concentrations of nHA.

PMID- 29470677
TI  - A critical view of the quest for brain structural markers of Albert Einstein's
      special talents (a pot of gold under the rainbow).
AB  - Assertions regarding attempts to link glial and macrostructural brain events with
      cognitive performance regarding Albert Einstein, are critically reviewed. One
      basic problem arises from attempting to draw causal relationships regarding
      complex, delicately interactive functional processes involving finely tuned
      molecular and connectivity phenomena expressed in cognitive performance, based on
      highly variable brain structural events of a single, aged, formalin fixed brain.
      Data weaknesses and logical flaws are considered. In other instances, similar
      neuroanatomical observations received different interpretations and conclusions,
      as those drawn, e.g., from schizophrenic brains. Observations on white matter
      events also raise methodological queries. Additionally, neurocognitive
      considerations on other intellectual aptitudes of A. Einstein were simply
      ignored.

PMID- 29470678
TI  - An integrated experimental and modeling approach to propose biotinylated PLGA
      microparticles as versatile targeting vehicles for drug delivery.
AB  - Polymeric microparticles with covalently attached biotin are proposed as
      versatile targeting vehicles for drug delivery. The proposed microparticles made
      of 85/15 poly (lactic-co-glycolic acid) (PLGA) will have biotin available on the
      outside of the particle for the further attachment with an avidin group. Taking
      advantage of biotin's high affinity for avidin, and avidin's well-known
      chemistry, the particle has the potential to be easily coated with a variety of
      targeting moieties. This paper focuses on the design and resulting effect of
      adding biotin to PLGA microparticles using an integrated experimental and
      modeling approach. A fluorescent-tagged avidin (488-streptavidin) was used to
      confirm the presence and bioavailability of biotin on the outside of the
      particles. For the purpose of this study, bovine serum albumin (BSA) was used as
      a model therapeutic drug. Microparticles were created using two different types
      of polyvinyl alcohol 88 and 98 mol% hydrolyzed, which were then analyzed for
      their size, morphology, and encapsulation capacity of BSA. Release studies
      performed in vitro confirmed the slow release of the BSA over a 28-day period.
      Based on these release profiles, a release kinetics model was used to further
      quantify the effect of biotinylation of PLGA microparticles on their release
      characteristics by quantitatively extracting the effective drug diffusivity and
      drug desorption rate from the release profiles. It was found that the
      biotinylation of the PLGA microparticles slowed down both the drug desorption and
      drug diffusion process, which confirmed that biotinylated PLGA microparticles can
      be used for controlled drug release. The presented technology, as well as the
      proposed integrated experimental and modeling approach, forms a solid foundation
      for future studies using a cell-specific ligand that can be attached to avidin
      and incorporated onto the microparticles for targeted delivery.

PMID- 29470679
TI  - Reply to correspondence by Smart and Watson.

PMID- 29470680
TI  - Changes in Skeletal Muscle and Body Weight on Sleeping Beauty Transposon-Mediated
      Transgenic Mice Overexpressing Pig mIGF-1.
AB  - Insulin-like growth factor (IGF-I) is an important growth factor in mammals, but
      the functions of the local muscle-specific isoform of insulin-like growth factor
      1 (mIGF-1) to skeletal muscle development have rarely been reported. To determine
      the effect of pig mIGF-1 on body development and muscle deposition in vivo and to
      investigate the molecular mechanisms, the transgenic mouse model was generated
      which can also provide experimental data for making transgenic pigs with pig
      endogenous IGF1 gene. We constructed a skeletal muscle-specific expression vector
      using 5'- and 3'-regulatory regions of porcine skeletal alpha-actin gene. The
      expression cassette was flanked with Sleeping Beauty transposon (SB)-inverted
      terminal repeats. The recombinant vector could strongly drive enhanced green
      fluorescence protein (EGFP) reporter gene expression specifically in mouse
      myoblast cells and porcine fetal fibroblast cells, but not in porcine kidney
      cells. The EGFP level driven by alpha-actin regulators was significantly stronger
      than that driven by cytomegalovirus promoters. These results indicated that the
      cloned alpha-actin regulators could effectively drive specific expression of
      foreign genes in myoblasts, and the skeletal muscle-specific expression vector
      mediated with SB transposon was successfully constructed. To validate the effect
      of pig mIGF-1 on skeletal muscle growth, transgenic mice were generated by
      pronuclear microinjection of SB-mediated mIGF-1 skeletal expression vector and SB
      transposase-expressing plasmid. The transgene-positive rates of founder mice and
      the next-generation F1 mice were 30% (54/180) and 90.1% (64/71), respectively.
      The mIGF-1 gene could be expressed in skeletal muscle specifically. The levels of
      mRNA and protein in transgenic mice were 15 and 3.5 times higher, respectively,
      than in wild-type mice. The body weights of F1 transgenic mice were significantly
      heavier than wild-type mice from the age of 8 weeks onwards. The paraffin
      embedded sections of gastrocnemius from 16-week-old transgenic male mice showed
      that the numbers of myofibers per unit were increased in comparison with those in
      the wild-type mice. mIGF-1 overexpression in mice skeletal muscle may promote
      myofibers hypertrophy and muscle production, and increased the average body
      weight of adult mice. Transgenic mice models can be generated by the mediation of
      SB transposon with high transgene efficiency.

PMID- 29470682
TI  - Structure and biocompatibility of poly(vinyl alcohol)-based and agarose-based
      monolithic composites with embedded divinylbenzene-styrene polymeric particles.
AB  - Macroporous monolithic composites with embedded divinylbenzene-styrene (DVB-ST)
      polymeric particles were prepared by cryogelation techniques using poly(vinyl
      alcohol) or agarose solutions. Scanning electron microscopy images showed
      multiple interconnected pores with an average diameter in the range of 4 to 180
      MUm and quite homogeneous distribution of DVB-ST particles in the composites.
      Biocompatibility of the composites was assessed by estimation of the C5a fragment
      of complement in the blood serum and concentration of fibrinogen in the blood
      plasma which contacted the composites. A time-dependent generation of C5a
      fragment indicated weak activation of the complement system. At the same time,
      the difference in fibrinogen concentration, one of the most important proteins in
      the coagulation system of the blood, between the pristine blood plasma and the
      plasma, circulated through the monolithic columns, was insignificant.

PMID- 29470681
TI  - A large-scale multiomics analysis of wheat stem solidness and the wheat stem
      sawfly feeding response, and syntenic associations in barley, Brachypodium, and
      rice.
AB  - The wheat stem sawfly (WSS), Cephus cinctus Norton (Hymenoptera: Cephidae), is an
      important pest of wheat and other cereals, threatening the quality and quantity
      of grain production. WSS larvae feed and develop inside the stem where they are
      protected from the external environment; therefore, pest management strategies
      primarily rely on host plant resistance. A major locus on the long arm of wheat
      chromosome 3B underlies most of the variation in stem solidness; however, the
      impact of stem solidness on WSS feeding has not been completely characterized.
      Here, we used a multiomics approach to examine the response to WSS in both solid-
      and semi-solid-stemmed wheat varieties. The combined transcriptomic, proteomic,
      and metabolomic data revealed that two important molecular pathways,
      phenylpropanoid and phosphate pentose, are involved in plant defense against WSS.
      We also detected a general downregulation of several key defense transcripts,
      including those encoding secondary metabolites such as DIMBOA, tricetin, and
      lignin, which suggested that the WSS larva might interfere with plant defense. We
      comparatively analyzed the stem solidness genomic region known to be associated
      with WSS tolerance in wild emmer, durum, and bread wheats, and described syntenic
      regions in the close relatives barley, Brachypodium, and rice. Additionally,
      microRNAs identified from the same genomic region revealed potential regulatory
      pathways associated with the WSS response. We propose a model outlining the
      molecular responses of the WSS-wheat interactions. These findings provide insight
      into the link between stem solidness and WSS feeding at the molecular level.

PMID- 29470683
TI  - Clinical significance of the 2016 WHO classification in Japanese patients with
      gliomas.
AB  - In this study, we retrospectively compared the prognostic value of the 2016 WHO
      classification with the former classification in 387 patients with glioma treated
      at our institution. According to the new classification, diagnoses included
      oligodendroglioma with isocitrate dehydrogenase (IDH) mutation and 1p/19q co
      deletion (5.4%), anaplastic oligodendroglioma with IDH mutation and 1p/19q co
      deletion (3.4%), diffuse astrocytoma IDH-mutated (3.9%), anaplastic astrocytoma
      IDH-mutated (2.8%), glioblastoma IDH-mutated (7.8%), glioblastoma IDH-wildtype
      (58.4%), diffuse midline glioma H3 K27M mutation (2.6%), oligodendroglioma NOS
      (1.3%), anaplastic oligodendroglioma NOS (0.8%), diffuse astrocytoma IDH-wildtype
      (2.8%), and anaplastic astrocytoma IDH-wildtype (10.9%). The prognoses of IDH
      mutated astrocytomas clearly varied according to tumor grade. However, we
      identified no survival difference between IDH-wildtype anaplastic astrocytomas
      and glioblastomas; additionally, these tumors showed similar gene expression
      profiles. After exclusion of those without 1p/19q co-deletion, patients with
      oligodendroglial tumors showed excellent survival regardless of tumor grade. Our
      evaluation of chromosomal aberrations suggests that the MAPK/PI3K pathway plays a
      role in acquired malignancy of astrocytic tumors, whereas TP53 participates in
      tumorigenesis. We suspect the RB pathway also plays a role in tumorigenesis of
      IDH-mutated gliomas. The new WHO classification more clearly reflects the
      tumorigenesis of gliomas and improves the prognostic power of classification.

PMID- 29470684
TI  - Comparative studies on osteogenic potential of micro- and nanofibre scaffolds
      prepared by electrospinning of poly(epsilon-caprolactone).
AB  - The biocompatibility and osteogenic potential of four fibrous scaffolds prepared
      by electrospinning of poly(epsilon-caprolactone) (PCL) was studied with MG-63
      osteoblast cells. Two different kinds of scaffolds were obtained by adjustment of
      spinning conditions, which were characterized as nano- or microfibrous. In
      addition of one nanofibrous, scaffold was made more hydrophilic by blending PCL
      with Pluronics F 68. Scaffolds were characterized by scanning electron microscopy
      and water contact angle measurements. Morphology and growth of MG63 cells seeded
      on the different scaffolds were investigated by confocal laser scanning
      microscopy after vital staining with fluorescein diacetate and by colorimetric
      assays. It was found that scaffolds composed of microfibres stipulated better
      growth conditions for osteoblasts probably by providing a real three-dimensional
      culture substratum, while nanofibre scaffolds restricted cell growth
      predominantly to surface regions. Osteogenic activity of cells was determined by
      alkaline phosphatase (ALP) and o-cresolphthalein complexone assay. It was
      observed that osteogenic activity of cells cultured in microfibre scaffolds was
      significantly higher than in nanofibre scaffolds regarding ALP activity. Overall,
      one can conclude that nanofibre scaffold provides better conditions for initial
      attachment of cells but does not provide advantages in terms of scaffold
      colonization and support of osteogenic activity compared to scaffolds prepared
      from microfibres.

PMID- 29470685
TI  - The effect of halogen light stimulation on duration of ultrasound parameters of
      biophysical profile: a randomized clinical trial.
AB  - INTRODUCTION: The objective is to assess if fetal halogen light stimulation can
      reduce the time needed to obtain a normal biophysical profile (BPP). METHODS:
      Patients scheduled for a BPP and who satisfied the inclusion criteria were
      prospectively randomized to halogen light stimulation and no stimulation groups.
      The study group was exposed to handheld halogen light for 10 s whenever fetal
      breathing, movement, or tone was absent through the first 5 min of BPP. The time
      required to achieve complete BPP score was recorded. In patients with complete
      BPP score who had delivery within 1 week after the test, perinatal morbidity was
      examined. RESULTS: A total of 598 patients were randomized (light = 302, no light
      = 296). There was no difference between the two groups in terms of gestational
      age, maternal age, body mass index, and indication for BPP except for preterm
      labor (light: 9%, no light: 4%, p = 0.03). Among the patients who had a normal
      BPP score (n = 507), the mean (light: 7.1 +/- 6 min, no light: 12.3 +/- 8 min, p
      < 0.0001) and median (light: 4.3, no light: 8, p = 0.004) time needed to complete
      the BPP score was significantly less in the light stimulation group than the no
      stimulation group. Perinatal outcomes were not different between groups who had
      delivery during the first week after BPP. CONCLUSION: Fetal halogen light
      stimulation can be utilized to reduce the time needed to complete a BPP. However,
      further studies should be conducted in order to determine the effect of this
      method on decreasing non-reassuring test results. CLINICAL TRIAL REGISTRATION:
      The study was submitted to the Registry of Clinical Trials on 04/20/2017
      (IRCT2017041633470N1). After IRCT registration on 06/07/2017, we recruited
      patients from 06/08/2017 till 10/15/2017.

PMID- 29470686
TI  - A case of stage IA pancreatic ductal adenocarcinoma accompanied with focal
      pancreatitis demonstrated by contrast-enhanced ultrasonography.
AB  - A patient with slight dilatation of the main pancreatic duct was followed-up with
      ultrasonography every 6 months as a high-risk case of pancreatic cancer. Twelve
      years later, a faint hypoechoic area 13 mm in diameter was first detected on the
      body of the pancreas. Contrast-enhanced ultrasonography revealed a well
      demarcated hypoenhanced area 8 mm in diameter and a hyperenhanced area with an
      unclear margin. The former was suspected to be a small pancreatic cancer lesion,
      and the latter to be focal pancreatitis accompanying cancer. However, contrast
      enhanced dynamic CT did not suggest any tumor, diagnosis of adenocarcinoma was
      confirmed with pancreatic juice cytology through endoscopic retrograde
      pancreatography. Surgical resection was performed, and the lesion was
      pathologically diagnosed as invasive ductal carcinoma as follows: pTS1 (1.0 cm),
      infiltrative type (pT1), stage IA. When comparing the images from contrast
      enhanced ultrasonography with the pathological findings, the hypoenhanced area
      corresponded to ductal adenocarcinoma, and the hyperenhanced area to focal
      pancreatitis. Contrast-enhanced ultrasonography was able to reveal detailed
      information on the focal lesion in the pancreas, and it was effective for the
      early diagnosis of pancreatic cancer.

PMID- 29470687
TI  - Surgical management of extensive dissecting thoracic aortic aneurysm via the semi
      clamshell approach.
AB  - BACKGROUND: We retrospectively evaluated the initial clinical experience of the
      surgical management of extensive dissecting thoracic aortic aneurysm (TAA) via
      the semi-clamshell approach. METHODS: Thirteen patients (3 women and 10 men, mean
      age 67 +/- 15 years) who underwent elective surgical intervention for extensive
      dissecting TAA via semi-clamshell approach in our institute between May 2007 and
      April 2017 participated in this study. Regarding surgical techniques, left
      thoracotomy with transverse sternotomy was initially performed via the third or
      fourth intercostal space following an incision from the right sternal borderline
      to the anterior axillary line on the left sternal borderline. Cardiopulmonary
      bypass was then established and extensive graft replacement was conducted with
      hypothermia. RESULTS: Extensive total arch replacement (TAR) was performed on 4
      patients, TAR with descending thoracic aortic replacement (DTAR) on 4, distal
      hemiarch replacement with DTAR on 3, and extensive graft replacement from the
      ascending to descending thoracic aorta on 2. There was one (7.7%) case of
      surgical and hospital mortality due to low-output syndrome. None of our patients
      developed respiratory failure requiring secondary tracheotomy; however, new-onset
      cerebrovascular infarction was noted in 2 (15.4%). No mediastinitis or serious
      infectious complications were observed after surgery. With a mean follow-up
      period of 45.1 +/- 44.1 months, a Kaplan-Meier analysis revealed that 1- and 5
      year survival rates were both 92.3%, respectively. CONCLUSIONS: The surgical
      management of extensive dissecting TAA by semi-clamshell approach may contribute
      to acceptable early clinical outcomes in high-risk patients, and represents an
      alternative surgical option in the current endovascular era.

PMID- 29470688
TI  - Spatial variability and geochemistry of rare earth elements in soils from the
      largest uranium-phosphate deposit of Brazil.
AB  - The Itataia uranium-phosphate deposit is the largest uranium reserve in Brazil.
      Rare earth elements (REEs) are commonly associated with phosphate deposits;
      however, there are no studies on the concentrations of REEs in soils of the
      Itataia deposit region. Thus, the objective of the research was to evaluate the
      concentration and spatial variability of REEs in topsoils of Itataia phosphate
      deposit region. In addition, the influence of soil properties on the geochemistry
      of REEs was investigated. Results showed that relatively high mean concentrations
      (mg kg-1) of heavy REEs (Gd 6.01; Tb 1.25; Ho 1.15; Er 4.05; Tm 0.64; Yb 4.61; Lu
      0.65) were found in surface soils samples. Soil properties showed weak influence
      on the geochemical behavior of REEs in soils, except for the clay content. On the
      other hand, parent material characteristics, such as P and U, had strong
      influence on REEs concentrations. Spatial distribution patterns of REEs in soils
      are clearly associated with P and U contents. Therefore, geochemical surveys
      aiming at the delineation of ore-bearing zones in the region can benefit from our
      data. The results of this work reinforce the perspective for co-mining of P, U
      and REEs in this important P-U reserve.

PMID- 29470690
TI  - Early introduction of complementary foods and childhood overweight in breastfed
      and formula-fed infants in the Netherlands: the PIAMA birth cohort study.
AB  - PURPOSE: To investigate whether early introduction of complementary foods (CF) is
      associated with an increased risk of overweight during childhood, and whether
      this association differs between formula-fed and breastfed infants. METHODS: We
      included 2611 participants that were born at term from a Dutch population-based
      birth cohort (n = 3963) designed to investigate the development of asthma and
      allergies. Parents kept records of their infant's age when CF were first
      introduced. Weight and height were parent reported yearly from age 1 to 8 years,
      and at ages 11, 14 and 17 years. We used multivariate generalized estimating
      equations analysis to investigate the association between timing of CF
      introduction (before 4 months vs at or after 4 months of age) and overweight at
      ages 1-17 years. RESULTS: Children with CF introduction before 4 months had
      higher odds of being overweight during childhood than children with CF
      introduction at or after 4 months (OR 1.32, 95% CI 1.19, 1.47). This association
      was observed in formula-fed infants (OR 1.51, 95% CI 1.17, 1.94) and breastfed
      infants (OR 1.32, 95% CI 1.19, 1.47). The duration of breastfeeding modified the
      association between CF introduction and overweight: children breastfed for
      shorter than 4 months, but not children breastfed for 4 months or longer with CF
      introduction before 4 months had higher odds of being overweight (OR 1.37, 95% CI
      1.19, 1.57 and 1.07, 95% CI 0.87, 1.32, respectively), compared to those with CF
      introduction at or after 4 months. CONCLUSIONS: In children born at term, formula
      fed infants and infants who were breastfed for shorter than 4 months, but not
      infants who were breastfed for 4 months or longer, had a higher risk of being
      overweight during childhood when being introduced to CF before 4 months of age.

PMID- 29470689
TI  - The nutritional and health attributes of kiwifruit: a review.
AB  - PURPOSE: To describe the nutritional and health attributes of kiwifruit and the
      benefits relating to improved nutritional status, digestive, immune and metabolic
      health. The review includes a brief history of green and gold varieties of
      kiwifruit from an ornamental curiosity from China in the 19th century to a crop
      of international economic importance in the 21st century; comparative data on
      their nutritional composition, particularly the high and distinctive amount of
      vitamin C; and an update on the latest available scientific evidence from well
      designed and executed human studies on the multiple beneficial physiological
      effects. Of particular interest are the digestive benefits for healthy
      individuals as well as for those with constipation and other gastrointestinal
      disorders, including symptoms of irritable bowel syndrome. The mechanisms of
      action behind the gastrointestinal effects, such as changes in faecal (stool)
      consistency, decrease in transit time and reduction of abdominal discomfort,
      relate to the water retention capacity of kiwifruit fibre, favourable changes in
      the human colonic microbial community and primary metabolites, as well as the
      naturally present proteolytic enzyme actinidin, which aids protein digestion both
      in the stomach and the small intestine. The effects of kiwifruit on metabolic
      markers of cardiovascular disease and diabetes are also investigated, including
      studies on glucose and insulin balance, bodyweight maintenance and energy
      homeostasis. CONCLUSIONS: The increased research data and growing consumer
      awareness of the health benefits of kiwifruit provide logical motivation for
      their regular consumption as part of a balanced diet. Kiwifruit should be
      considered as part of a natural and effective dietary strategy to tackle some of
      the major health and wellness concerns around the world.

PMID- 29470691
TI  - Even effect of milk protein and carbohydrate intake but no further effect of
      heavy resistance exercise on myofibrillar protein synthesis in older men.
AB  - PURPOSE: The responsiveness of older individuals' skeletal muscle to anabolic
      strategies may be impaired. However, direct comparisons within the same
      experimental setting are sparse. The aim of this study was to assess the resting
      and post-resistance exercise muscle protein synthesis rates in response to two
      types of milk protein and carbohydrate using a unilateral exercise leg model.
      METHODS: Twenty-seven older (69 +/- 1 year, mean +/- SE) men were randomly
      assigned one of three groups: Whey hydrolysate (WH), caseinate (CAS), or
      carbohydrate (CHO). By applying stable isotope tracer techniques (L
      [15N]phenylalanine), the fasted-rested (basal) myofibrillar fractional synthesis
      rate (FSR) was measured. Hereafter, FSR was measured in the postprandial phase
      (0.45 g nutrient/kg LBM) in both legs, one rested (fed-rest) and one exercised
      (10 * 8 reps at 70% 1RM; fed-exercise). In addition, the activity of p70S6K and
      venous plasma insulin, phenylalanine, and leucine concentrations were measured.
      RESULTS: Insulin, phenylalanine, and leucine concentrations differed markedly
      after intake of the different study drinks. The basal FSR in WH, CAS, and CHO
      were 0.027 +/- 0.003, 0.030 +/- 0.003, and 0.030 +/- 0.004%/h, the fed-rested FSR
      were 0.043 +/- 0.004, 0.045 +/- 0.003, and 0.035 +/- 0.004%/h, and the fed
      exercised FSR were 0.041 +/- 0.004, 0.043 +/- 0.004, and 0.034 +/- 0.004%/h,
      respectively. No significant differences were observed at any state between the
      groups. Fed-rested- and fed-exercised FSR were higher than basal (P < 0.001). 3 h
      after exercise and feeding, no significant group differences were detected in the
      activity of p70S6K. CONCLUSIONS: Milk protein and carbohydrate supplementation
      stimulate myofibrillar protein synthesis in older men, with no further effect of
      heavy resistance exercise within 0-3 h post exercise.

PMID- 29470692
TI  - Validation of the Chowdhury overall survival score in patients with melanoma
      brain metastasis treated with Gamma Knife Radiosurgery.
AB  - Melanoma brain metastases (MBM) are common in patients with stage IV disease. For
      Gamma Knife radiosurgery (GKRS) on MBM, risk scores such as RPA and melanoma-GPA
      aid to identify prognostic subgroups. This study aimed to validate the overall
      survival (OS) risk score developed by Chowdhury et al. in our center's patient
      cohort. A total of 104 MBM patients were treated with GKRS between 1/1/2002 and
      31/12/2014 in our institution. Patients were categorized according to RPA,
      melanoma-GPA and Chowdhury OS score. The Kaplan-Meier method was used to estimate
      overall survival, and predicted survival probabilities were calculated for
      calibration. Cox proportional hazards regressions were performed to identify
      additional risk factors. Overall, median follow-up time was 80 months, while
      median OS (mOS) after GKRS was 6 months. Stratified according to the Chowdhury OS
      score, mOS in the high, medium and low risk group was 3.4, 7.1, and 10.0 months,
      respectively. The addition of other patient or disease characteristics to the
      Chowdhury OS model did not improve its performance. The C-index of the melanoma
      GPA was 0.46 while the Chowdhury OS had an index of 0.67. In comparison with the
      RPA and melanoma-GPA, the Chowdhury OS score more accurately distinguished
      between separate risk groups among patients with MBM treated with GKRS. Contrary
      to the original study by Chowdhury, follow-up time was sufficient here for the
      low-risk group to reach the mOS time of 10 months.

PMID- 29470693
TI  - Anti-inflammatory, anti-rheumatic and analgesic activities of 2-(5-mercapto-1,3,4
      oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS) in rodents.
AB  - Chronic inflammation is pathologically associated with various clinical
      conditions such as rheumatoid arthritis. Several anti-inflammatory and analgesic
      drugs currently available in market presents a wide range of problems. Therefore,
      the current study was aimed to evaluate anti-inflammatory and analgesic
      activities of newly synthesized compound 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N
      propylbenzenesulphonamide (MOPBS). Carrageenan and CFA-induced models were
      developed for evaluation of anti-inflammatory and analgesic activity.
      Quantitative real-time PCR (qRT-PCR) was performed to determine the mRNA
      expression levels of inflammatory mediators. Pain behaviours were evaluated by
      performing Von Frey, Randall Selitto, cold acetone and hot plate test
      respectively. X-ray imaging and haematoxylin and eosin (H&E) staining were
      performed for examination of soft tissues of treated mice paw. Additionally,
      Kodzeila's screen test and weight test were performed for determination of any
      side effects on motor function and muscle strength. Acute pretreatment of animals
      with MOPBS (1, 10, 50 and 100 mg/kg, i.p.) produced a significant reduction of
      paw oedema against carrageenan-induced acute inflammation as well as notable
      inhibition of mechanical hyperalgesia, allodynia and thermal hyperalgesia.
      Similarly, in chronic inflammation model, administration of MOPBS (50 mg/kg,
      i.p.) produced a remarkable reduction of paw oedema. Additionally, MOPBS
      pretreatment showed a significant inhibition of thermal hyperalgesia, mechanical
      allodynia, and mechanical hyperalgesia in chronic arthritis model. Several pro
      inflammatory mediators such as nitric oxide (NO), vascular endothelial growth
      factor (VEGF), interleukins (IL-1beta, IL-6) and tumor necrosis factor-alpha (TNF
      alpha) were inhibited by MOPBS treatment in blood plasma and paw tissues,
      respectively. MOPBS also enhanced the mRNA expression levels of nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2), superoxide dismutase (SOD2) and heme
      oxygenase (HO-1) and in turn reduced arthritis severity and inflammation.
      Furthermore, anti-inflammatory data were confirmed by X-rays and histological
      analysis. MOPBS pretreatment did not produce any apparent toxic effect on
      gastric, kidney and liver function and on muscle strength and motor function.
      Hence, the present data suggest that MOPBS might be a candidate for several
      chronic inflammatory diseases such RA and other auto-immune diseases.

PMID- 29470694
TI  - New prospects of mesenchymal stem cells for ameliorating temporal lobe epilepsy.
AB  - Temporal lobe epilepsy (TLE) is present in 30% of epileptic patients and does not
      respond to conventional treatments. Bone marrow derived mesenchymal stem cells
      (BMSCs) induce endogenous neural stem cells, inhibit neurodegeneration, and
      promote brain self-repair mechanisms. The present study addresses the feasibility
      of BMSCs transplantation against pilocarpine-induced TLE experimentally. BMSCs
      were injected either intravenously (IV) or in hippocampus bilaterally (IC).
      Increased cell count of BMSCs was achieved via IC route. BMSCs treatment
      ameliorated the pilocarpine-induced neurochemical and histological changes,
      retained amino acid neurotransmitters to the normal level, downregulated the
      immunoreactivity to insulin growth factor-1 receptor, synaptophysin, and caspase
      3 and reduced oxidative insult and inflammatory markers detected in epileptic
      model. It is worth noting that BMSCs IC-administered showed more pronounced
      effects than those administered via IV route. BMSCs transplantation presents a
      promise for TLE treatment that has to be elucidated clinically.

PMID- 29470696
TI  - Additive hazards model with auxiliary subgroup survival information.
AB  - The semiparametric additive hazards model is an important way for studying the
      effect of potential risk factors for right-censored time-to-event data. In this
      paper, we study the additive hazards model in the presence of auxiliary subgroup
      [Formula: see text]-year survival information. We formulate the known auxiliary
      information in the form of estimating equations, and combine them with the
      conventional score-type estimating equations for the estimation of the regression
      parameters based on the maximum empirical likelihood method. We prove that the
      new estimator of the regression coefficients follows asymptotically a
      multivariate normal distribution with a sandwich-type covariance matrix that can
      be consistently estimated, and is strictly more efficient, in an asymptotic
      sense, than the conventional one without incorporation of the available auxiliary
      information. Simulation studies show that the new proposal has substantial
      advantages over the conventional one in terms of standard errors, and with the
      accommodation of more informative information, the proposed estimator becomes
      more competing. An AIDS data example is used for illustration.

PMID- 29470695
TI  - A banana NAC transcription factor (MusaSNAC1) impart drought tolerance by
      modulating stomatal closure and H2O2 content.
AB  - KEY MESSAGE: MusaSNAC1 function in H2O2 mediated stomatal closure and promote
      drought tolerance by directly binding to CGT[A/G] motif in regulatory region of
      multiple stress-related genes. Drought is a abiotic stress-condition, causing
      reduced plant growth and diminished crop yield. Guard cells of the stomata
      control photosynthesis and transpiration by regulating CO2 exchange and water
      loss, thus affecting growth and crop yield. Roles of NAC (NAM, ATAF1/2 and CUC2)
      protein in regulation of stress-conditions has been well documented however,
      their control over stomatal aperture is largely unknown. In this study we report
      a banana NAC protein, MusaSNAC1 which induced stomatal closure by elevating H2O2
      content in guard cells during drought stress. Overexpression of MusaSNAC1 in
      banana resulted in higher number of stomata closure causing reduced water loss
      and thus elevated drought-tolerance. During drought, expression of GUS (beta
      glucuronidase) under P MusaSNAC1 was remarkably elevated in guard cells of
      stomata which correlated with its function as a transcription factor regulating
      stomatal aperture closing. MusaSNAC1 is a transcriptional activator belonging to
      SNAC subgroup and its 5'-upstream region contain multiple Dof1 elements as well
      as stress-associated cis-elements. Moreover, MusaSNAC1 also regulate multiple
      stress-related genes by binding to core site of NAC-proteins CGT[A/G] in their 5'
      upstream region. Results indicated an interesting mechanism of drought tolerance
      through stomatal closure by H2O2 generation in guard cells, regulated by a NAC
      protein in banana.

PMID- 29470697
TI  - Reliability analysis of load-sharing systems with memory.
AB  - The load-sharing model has been studied since the early 1940s to account for the
      stochastic dependence of components in a parallel system. It assumes that, as
      components fail one by one, the total workload applied to the system is shared by
      the remaining components and thus affects their performance. Such dependent
      systems have been studied in many engineering applications which include but are
      not limited to fiber composites, manufacturing, power plants, workload analysis
      of computing, software and hardware reliability, etc. Many statistical models
      have been proposed to analyze the impact of each redistribution of the workload;
      i.e., the changes on the hazard rate of each remaining component. However, they
      do not consider how long a surviving component has worked for prior to the
      redistribution. We name such load-sharing models as memoryless. To remedy this
      potential limitation, we propose a general framework for load-sharing models that
      account for the work history. Through simulation studies, we show that an
      inappropriate use of the memoryless assumption could lead to inaccurate inference
      on the impact of redistribution. Further, a real-data example of plasma display
      devices is analyzed to illustrate our methods.

PMID- 29470698
TI  - Permanent Hypoparathyroidism After Total Thyroidectomy in Children: Results from
      a National Registry.
AB  - INTRODUCTION: Hypoparathyroidism is the most common complication following
      thyroidectomy. There are few population-based reports on the rate of
      hypoparathyroidism in children. The incidence of medical treatment of permanent
      hypoparathyroidism in children is reported using a national registry. METHODS:
      The study population included patients below 18 years of age undergoing total
      thyroidectomy reported to the Scandinavian Quality Registry for Thyroid,
      Parathyroid and Adrenal Surgery 2004-2014. Patients with previous thyroid or
      parathyroid surgery or treatment with vitamin D before surgery were excluded from
      analysis. Permanent postoperative hypoparathyroidism was defined as treatment
      with vitamin D for more than 6 months after thyroidectomy. Risk factors for
      permanent hypoparathyroidism were calculated with uni- and multivariable logistic
      regression. Using data from the Swedish Inpatient Registry, rates of readmissions
      and annual number of days in hospital after total thyroidectomy were compared
      between patients with and without permanent hypoparathyroidism. RESULTS: Some 274
      children (215 girls and 59 boys) underwent total thyroidectomy. The median age
      was 14 (range 0-17) years. Indications for surgery were Graves' disease (214,
      78.1%), other benign disease (27, 9.9%) and thyroid cancer (33, 12%). Median
      follow-up was 4.8 years. Twenty (7.3%) children developed permanent
      hypoparathyroidism. No statistically significant risk factors for permanent
      hypoparathyroidism were identified. Rates of readmission and annual number of
      days in hospital after discharge were similar in patients with and without
      permanent hypoparathyroidism. CONCLUSIONS: The rate of permanent
      hypoparathyroidism following total thyroidectomy in children was high and is a
      cause of concern.

PMID- 29470699
TI  - A Nested Case-Control Study on the Risk of Surgical Site Infection After Thyroid
      Surgery.
AB  - INTRODUCTION: It is unclear if antibiotic prophylaxis reduces the risk of
      surgical site infection (SSI) in thyroid surgery. This study assessed risk
      factors for SSI and antibiotic prophylaxis in subgroups of patients. METHOD AND
      DESIGN: A nested case-control study on patients registered in the Swedish
      National Register for Endocrine Surgery was performed. Patients with SSI were
      matched 1:1 by age and gender to controls. Additional information on patients
      with SSI and controls was queried from attending surgeons using a questionnaire.
      Risk factors for SSI were evaluated by logistic regression analysis and presented
      as odds ratio (OR) with 95% confidence interval (CI). RESULTS: There were 9494
      operations; 109 (1.2%) patients had SSI. Patients with SSI were older (median 53
      vs. 49 years) than patients without SSI p = 0.01 and more often had a cancer
      diagnosis 23 (21.1%) versus 1137 (12.1%) p = 0.01. In the analysis of patients
      with SSI versus controls, patients with SSI more often had post-operative
      drainage 68 (62.4%) versus 46 (42.2%) p = 0.01 and lymph node surgery 40 (36.7%)
      versus 14 (13.0%) p < 0.01, and both were independent risk factors for SSI, drain
      OR 1.82 (CI 1.04-3.18) and lymph node dissection, OR 3.22 (95% CI 1.32-7.82). A
      higher number of 26(62%) patients with independent risk factors for SSI and
      diagnosed with SSI did not receive antibiotic prophylaxis. Data were missing for
      8 (31%) patients. CONCLUSION: Lymph node dissection and drain are independent
      risk factors for SSI after thyroidectomy. Antibiotic prophylaxis might be
      considered in patients with these risk factors.

PMID- 29470700
TI  - Incidental Diagnosis of Parathyroid Lesions by Preoperative Use of Next
      Generation Molecular Testing.
AB  - BACKGROUND: Parathyroid glands can mimic thyroid follicular lesions on fine
      needle aspiration (FNA) cytology and can lead to unnecessary or incorrect
      surgery. Newer molecular panel tests using next-generation sequencing (NGS)
      include analysis of cell type-specific gene expression profiles such as
      parathyroid. The study aim is to determine the frequency and clinical
      implications of parathyroid tissue identification by molecular testing in
      cytologically indeterminate "thyroid" lesions. METHODS: Molecular analysis of
      indeterminate thyroid FNA specimens is obtained routinely and relies on
      amplification-based NGS inclusive of PTH-specific expression profiles. For this
      study, we retrospectively examined the clinical data and management of patients
      with molecular results positive for PTH expression from May 2014 until May 2016.
      RESULTS: Among 4765 consecutive patients with indeterminate cytology for a
      presumed thyroid nodule, NGS instead indicated a parathyroid lesion in 20
      patients (0.42%). The clinical data of 15 patients were available, and the
      subsequent clinical management was altered in 93% (14/15 patients), including
      five (33%) eucalcemic patients who could avoid unnecessary surgery. Primary
      hyperparathyroidism was not suspected in seven patients until the molecular
      analysis results, and primary hyperparathyroidism was diagnosed in one (14%).
      During parathyroid exploration, most patients (6/8, 75%) required concurrent
      thyroidectomy or lobectomy, but thyroid preservation was still possible in two
      patients. A parathyroid gland was histologically confirmed in 89%. CONCLUSIONS:
      In 0.42% of patients with indeterminate cytology results, next-generation
      molecular results will indicate the presence of a parathyroid lesion. When this
      occurs, it is accurate and can robustly impact clinical management (93%).

PMID- 29470701
TI  - Preservation of gonadal function in women undergoing chemotherapy: a systematic
      review and meta-analysis of the potential role for gonadotropin-releasing hormone
      agonists.
AB  - PURPOSE: To evaluate the available randomized controlled trials (RCTs) in the
      literature investigating the use of gonadotropin-releasing hormone agonist
      (GnRHa) co-treatment for ovarian preservation in women receiving chemotherapy.
      METHODS: A systematic review of the literature was performed from 1960 through
      2017 to identify relevant RCTs. Included patients had lymphoma, ovarian cancer,
      or breast cancer. The primary outcome was the proportion of women who retained
      ovarian function after chemotherapy. Extracted data points included study design,
      patient characteristics, and proportion of women who developed premature ovarian
      failure (POF). A risk of bias assessment was performed according to the criteria
      outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The
      pooled odds ratio was calculated, and outcomes of individual studies were
      compared using the random-effects model with the inverse-variance method and the
      DerSimonian-Laird estimator. RESULTS: Twenty-nine RCTs were identified, and 10
      met criteria for inclusion in the meta-analysis. An analysis of patients who did
      not develop POF after chemotherapy revealed eight studies supporting the use of
      GnRHa (OR 1.83; 95% CI 1.34-2.49). The duration of benefit of GnRHa is unclear.
      An analysis of three studies with outcome data at 2 years revealed a non
      significant OR of 0.53 (95% CI 0.22-1.30) for the preservation of ovarian
      function with GnRHa treatment. CONCLUSION: GnRHa may have a protective effect
      against the development of POF after gonadotoxic chemotherapy; however, the
      duration of benefit is unclear and requires further study.

PMID- 29470702
TI  - The mutual benefits of research in wild animal species and human-assisted
      reproduction.
AB  - Studying the reproductive biology of wild animal species produces knowledge
      beneficial to their management and conservation. However, wild species also share
      intriguing similarities in reproductive biology with humans, thereby offering
      alternative models for better understanding the etiology of infertility and
      developing innovative treatments. The purpose of this review is to raise
      awareness in different scientific communities about intriguing connections
      between wild animals and humans regarding infertility syndromes or improvement of
      fertility preservation. The objectives are to (1) highlight commonalities between
      wild species and human fertility, (2) demonstrate that research in wild species
      assisted reproductive technologies can greatly enhance success in human
      reproductive medicine, and (3) recognize that human fertility preservation is
      highly inspiring and relevant to wild species conservation. In addition to having
      similar biological traits in some wild species and humans, the fact of sharing
      the same natural environment and the common needs for more options in fertility
      preservation are strong incentives to build more bridges that will eventually
      benefit both animal conservation and human reproductive medicine.

PMID- 29470703
TI  - Guide for health professionals addressing oral care for individuals in
      oncological treatment based on scientific evidence.
AB  - OBJECTIVE: Oncological treatment can cause changes in the oral cavity
      compromising oral functions. The aim of the study was, based on a systematic
      review, to draft a guide directed at the team of health professionals involved in
      the oral care of oncological patients. METHODS: A systematic search of the
      literature was performed for articles published between 2000 and April 2017.
      Searches were made of electronic databases and hand search. The inclusion
      criteria were systematic reviews of randomized clinical trials (RCTs) and RCTs
      published in English, involving pediatric and adult oncological patients and
      focused on the prevention and treatment of oral complications as well as studies
      addressing the maintenance of oral health. Among the 1237 studies identified, 129
      were pre-selected and 54 were selected to form the basis for the clinical guide.
      RESULTS: The studies analyzed stress the need for oral assessments as well as
      preventive and curative actions prior to oncological treatment. To minimize the
      severity of oral problems, the studies emphasize daily oral care, the treatment
      of xerostomia with saliva substitute and hydration, and low-level laser therapy,
      nystatin, acyclovir, respectively, for the prevention and treatment of oral
      mucositis, oral candidiasis, and infection by herpes simplex virus. Thus, the
      guide produced addresses oral assessments and professional and home care before,
      during, and after oncological treatment. CONCLUSION: The guide drafted has the
      function of assisting health professionals involved in the oral care of patients
      with cancer, enabling the prevention or treatment of oral complications stemming
      from oncological treatment.

PMID- 29470704
TI  - Relationship between sleep and exercise as colorectal cancer survivors transition
      off treatment.
AB  - PURPOSE: The primary objective of this study was to evaluate the relationship
      between exercise and sleep disturbance in a sample of individuals diagnosed with
      stage I, II, and III colorectal cancer (CRC) as patients transitioned off first
      line treatment. We also sought to identify heterogeneity in the relationship
      between sleep disturbance and exercise. METHODS: Data were obtained from the MY
      Health study, a community-based observational study of adults diagnosed with
      cancer. Patient-Reported Outcomes Measurement Information System(r) (PROMIS)
      measures (e.g., PROMIS Sleep) were administered, and participants self-reported
      demographics, comorbidities, cancer treatment, and exercise. Regression mixture
      and multiple regression models were used to evaluate the relationship between
      sleep disturbance and exercise cross-sectionally at an average of 10 months after
      diagnosis, and the change in sleep disturbance over a 7-month period, from
      approximately 10 to 17 months post-diagnosis. RESULTS: Patients whose exercise
      was categorized as likely at or above American College of Sports Medicine's
      guidelines did not report statistically better sleep quality compared to patients
      who were classified as not active. However, retirement (B = - 2.4), anxiety (B =
      0.21), and fatigue (B = 0.24) had statistically significant relationships with
      sleep disturbance (p < 0.05). Increase in exercise was not significantly
      associated with a decrease in sleep disturbance. No statistical heterogeneity was
      revealed in the relationship between sleep and exercise. CONCLUSIONS: Further
      prospective research using an objective measure of exercise is warranted to
      confirm or refute the nature of the relationship between exercise and sleep
      disturbance in individuals diagnosed with CRC transitioning off first-line
      treatment.

PMID- 29470706
TI  - Reduced proliferation capacity of lung cells in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND AND OBJECTIVES: The prevalence of chronic obstructive pulmonary
      disease (COPD) and lung emphysema increases with age and both lung diseases are
      again risk factors for lung cancer. Since a reduced capacity of fibroblasts for
      proliferation is a good indicator of tissue aging, we studied the cell
      proliferation of lung fibroblasts from normal and tumor tissue of lung cancer
      patients depending on lung comorbidities. MATERIAL AND METHODS: Fibroblasts were
      isolated from tumor and normal lung tissue of 40 lung cancer patients. Cumulative
      population doubling (CPD) was determined to assess the proliferation capacity,
      and the PCR technique was used to measure telomere lengths. Since many patients
      had previously been exposed to severe air pollution, we also studied the effect
      of air pollution particles on the fibroblast CPD in vitro. RESULTS: Fibroblasts
      from tumor and normal lung tissue had comparable CPDs; however, the CPD of
      fibroblasts from both tumor and normal lung tissue was significantly reduced in
      patients also suffering from COPD. This CPD reduction was highest in COPD
      patients who had already developed emphysema or were smokers. A significant
      correlation between CPD and telomere length was identified only for fibroblasts
      of non-COPD patients. Further studies also showed an adverse effect of air
      pollution particles on the CPD of lung fibroblasts. CONCLUSION: Lung cells of
      COPD patients are characterized by accelerated senescence which must have been
      initiated prior to lung tumorigenesis and cannot depend on telomere shortening
      only. In addition to smoking as a known risk factor for COPD and lung cancer, air
      pollution particles could be another reason for the accelerated senescence of
      lung cells.

PMID- 29470705
TI  - The effects of high-dose calcitriol and individualized exercise on bone
      metabolism in breast cancer survivors on hormonal therapy: a phase II feasibility
      trial.
AB  - INTRODUCTION: Cancer treatment-induced bone loss (CTIBL) is a long-term side
      effect of breast cancer therapy. Both calcitriol and weight-bearing exercise
      improve bone metabolism for osteoporotic patients, but are unproven in a breast
      cancer population. We used a novel high-dose calcitriol regimen with an
      individualized exercise intervention to improve bone metabolism in breast cancer
      survivors. METHODS: We accrued 41 subjects to this open label, 2 * 2 factorial,
      randomized feasibility trial. Breast cancer survivors were randomized to receive
      the following: (1) calcitriol (45 micrograms/week), (2) individualized exercise
      with progressive walking and resistance training, (3) both, or (4) a daily
      multivitamin (control condition) for 12 weeks. Primary outcomes included changes
      in biomarkers of bone formation, bone resorption, and the bone remodeling index,
      a composite measure of bone formation and resorption. Safety measures included
      clinical and biochemical adverse events. A main effect analysis was used for
      these endpoints. RESULTS: Hypercalcemia was limited to three grade I cases with
      no grade >= 2 cases. Among exercisers, 100% engaged in the prescribed aerobic
      training and 44.4% engaged in the prescribed resistance training. Calcitriol
      significantly improved bone formation (Cohen's d = 0.64; p < 0.01), resulting in
      a non-significant increase in the bone remodeling index (Cohen's d = 0.21; p =
      31). Exercise failed to improve any of the bone biomarkers. CONCLUSIONS: Both
      calcitriol and exercise were shown to be feasible and well tolerated. Calcitriol
      significantly improved bone formation, resulting in a net increase of bone
      metabolism. Compliance with the exercise intervention was sub-optimal, which may
      have led to a lack of effect of exercise on bone metabolism.

PMID- 29470707
TI  - Modeling, simulation, and employing dilution-dialysis microfluidic chip (DDMC)
      for heightening proteins refolding efficiency.
AB  - Miniaturized systems based on the principles of microfluidics are widely used in
      various fields, such as biochemical and biomedical applications. Systematic
      design processes are demanded the proper use of these microfluidic devices based
      on mathematical simulations. Aggregated proteins (e.g., inclusion bodies) in
      solution with chaotropic agents (such as urea) at high concentration in
      combination with reducing agents are denatured. Refolding methods to achieve the
      native proteins from inclusion bodies of recombinant protein relying on
      denaturant dilution or dialysis approaches for suppressing protein aggregation is
      very important in the industrial field. In this paper, a modeling approach is
      introduced and employed that enables a compact and cost-effective method for on
      chip refolding process. The innovative aspect of the presented refolding method
      is incorporation dialysis and dilution. Dilution-dialysis microfluidic chip
      (DDMC) increases productivity folding of proteins with the gradual reduction of
      the amount of urea. It has shown the potential of DDMC for performing refolding
      of protein trials. The principles of the microfluidic device detailed in this
      paper are to produce protein on the dilution with slow mixing through diffusion
      of a denatured protein solution and stepwise dialysis of a refolding buffer
      flowing together and the flow regime is creeping flow. The operation of DDMC was
      modeled in two dimensions. This system simulated by COMSOL Multiphysics Modeling
      Software. The simulation results for a microfluidic refolding chip showed that
      DDMC was deemed to be perfectly suitable for control decreasing urea in the fluid
      model. The DDMC was validated through an experimental study. According to the
      results, refolding efficiency of denaturant Hen egg white lysozyme (HEWL) (EC
      3.2.1.17) used as a model protein was improved. Regard to the remaining activity
      test, it was increased from 42.6 in simple dilution to 93.7 using DDMC.

PMID- 29470708
TI  - The wound response in fresh-cut lettuce involves programmed cell death events.
AB  - In this work, the involvement of programmed cell death (PCD) in the wound-induced
      postharvest browning disorder and senescence in butterhead lettuce (Lactuca
      sativa L.) fresh-cuts was studied. At the wounded (cut, bruised) sites, rapid
      browning, loss of chlorophyll and massive cell death, accompanied with
      accumulation of reactive oxygen species and increased electrolyte leakage
      occurred in a narrow strip of tissue adjacent the injury. The dead cell
      morphology (protoplast and nuclei shrinkage) together with the biochemical and
      physiological changes resembled necrotic PCD type. With a slight delay post
      wounding, senescence associated with similar cell death features was initiated in
      distant non-wounded sites. In addition to necrotic PCD, both in wounded and
      senescing tissue, the appearance of empty cell corpses was observed, indicating
      that part of the cells might undergo vacuolar PCD (self-digestion of cellular
      content after vacuole collapse). The wounding-induced local cell death at the
      primary site of damage suggested that PCD may serve as a mechanism to seal-off
      the wound by building a physical barrier of dead cells. However, the cell death
      at sites remote from the wound suggests the distribution of long-distance
      senescence-inducing wound messengers. Trichomes in unwounded tissue often were
      the first to show H2O2 accumulation and dead cells; thereafter, the elevated H2O2
      and cell death appeared in connecting cells and senescence progressed over larger
      areas. This suggests that trichomes may contribute to mediating the wound
      signalling leading to subsequent senescence. Our findings demonstrate that PCD is
      an integral part of the wound syndrome in fresh-cut lettuce.

PMID- 29470709
TI  - Arctic, Antarctic, and temperate green algae Zygnema spp. under UV-B stress:
      vegetative cells perform better than pre-akinetes.
AB  - Species of Zygnema form macroscopically visible mats in polar and temperate
      terrestrial habitats, where they are exposed to environmental stresses. Three
      previously characterized isolates (Arctic Zygnema sp. B, Antarctic Zygnema sp. C,
      and temperate Zygnema sp. S) were tested for their tolerance to experimental UV
      radiation. Samples of young vegetative cells (1 month old) and pre-akinetes (6
      months old) were exposed to photosynthetically active radiation (PAR, 400-700 nm,
      400 MUmol photons m-2 s-1) in combination with experimental UV-A (315-400 nm, 5.7
      W m-2, no UV-B), designated as PA, or UV-A (10.1 W m-2) + UV-B (280-315 nm, 1.0 W
      m-2), designated as PAB. The experimental period lasted for 74 h; the radiation
      period was 16 h PAR/UV-A per day, or with additional UV-B for 14 h per day. The
      effective quantum yield, generally lower in pre-akinetes, was mostly reduced
      during the UV treatment, and recovery was significantly higher in young
      vegetative cells vs. pre-akinetes during the experiment. Analysis of the
      deepoxidation state of the xanthophyll-cycle pigments revealed a statistically
      significant (p < 0.05) increase in Zygnema spp. C and S. The content of UV
      absorbing phenolic compounds was significantly higher (p < 0.05) in young
      vegetative cells compared to pre-akinetes. In young vegetative Zygnema sp. S,
      these phenolic compounds significantly increased (p < 0.05) upon PA and PAB.
      Transmission electron microscopy showed an intact ultrastructure with massive
      starch accumulations at the pyrenoids under PA and PAB. A possible increase in
      electron-dense bodies in PAB-treated cells and the occurrence of cubic membranes
      in the chloroplasts are likely protection strategies. Metabolite profiling by non
      targeted RP-UHPLC-qToF-MS allowed a clear separation of the strains, but could
      not detect changes due to the PA and PAB treatments. Six hundred seventeen
      distinct molecular masses were detected, of which around 200 could be annotated
      from databases. These results indicate that young vegetative cells can adapt
      better to the experimental UV-B stress than pre-akinetes.

PMID- 29470710
TI  - Risk stratification, genomic data and the law.
AB  - Risk prediction models have a key role in stratified disease prevention, and the
      incorporation of genomic data into these models promises more effective
      personalisation. Although the clinical utility of incorporating genomic data into
      risk prediction tools is increasingly compelling, at least for some applications
      and disease types, the legal and regulatory implications have not been examined
      and have been overshadowed by discussions about clinical and scientific utility
      and feasibility. We held a workshop to explore relevant legal and regulatory
      perspectives from four EU Member States: France, Germany, the Netherlands and the
      UK. While we found no absolute prohibition on the use of such data in those
      tools, there are considerable challenges. Currently, these are modest and result
      from genomic data being classified as sensitive data under existing Data
      Protection regulation. However, these challenges will increase in the future
      following the implementation of EU Regulations on data protection which take
      effect in 2018, and reforms to the governance of the manufacture, development and
      use of in vitro diagnostic devices to be implemented in 2022. Collectively these
      will increase the regulatory burden placed on these products as risk
      stratification tools will be brought within the scope of these new Regulations.
      The failure to respond to the challenges posed by the use of genomic data in
      disease risk stratification tools could therefore prove costly to those
      developing and using such tools.

PMID- 29470713
TI  - Health-related quality of life in patients undergoing cervico-thoracic
      osteotomies for fixed cervico-thoracic kyphosis in patients with ankylosing
      spondylitis.
AB  - PURPOSE: Ankylosing spondylitis (AS) can result in severe cervico-thoracic
      kyphotic deformity (CTKD). Few studies have addressed the relationship between
      cervico-thoracic osteotomies in AS and health-related quality of life scores. The
      aim of this study is to evaluate the impact of cervico-thoracic osteotomy (CTO)
      on improving quality of life for patients with fixed CTKD. METHODS: A database of
      all patients who underwent a CTO for CTKD in patients with AS was created. Data
      entered into the database consisted of patients' demographics and comorbidities,
      as well as surgical, clinical and radiological data. The outcome measures used in
      our study were Neck Disability Index (NDI), EuroQol 5D-5L (EQ-5D-5L) and Visual
      Analogue Scale. We also measured the following radiological parameters: chin-brow
      to vertical angle (CBVA), C7-Slope, C2-7 angle, Regional Kyphosis Angle, C2-C7
      sagittal vertical axis (SVA) and C7-S1 SVA. RESULTS: A total of 13 male patients
      with AS were included in our study. The mean age was 57.5 years (40-74); and mean
      follow-up was 37.6 months (12-78). Following the C7-T1 osteotomy (10 Smith
      Peterson Osteotomies and 3 Pedicle Subtraction Osteotomies), NDI improved from a
      mean of 65.54 (SD 8.95) to a mean of 22.09 (SD 6.99). The EQ-5D-5L improved from
      a mean of 0.41 (SD 0.16) to 0.86 (SD 0.088). Pre-operative CBVA was on average 54
      degrees  (40 degrees -75 degrees ) and post-operative was 7 degrees  (2 degrees 
      12 degrees ). There were no major complications, 1 superficial infection and 5
      minor nerve root irritations. CONCLUSIONS: Cervical osteotomy for the management
      of fixed flexion deformity of cervical spine in ankylosing spondylitis is a safe
      procedure and can result in restoration of horizontal gaze and sagittal balance
      with significant improvement of the patient's health-related quality of life.
      These slides can be retrieved under Electronic Supplementary Material.

PMID- 29470711
TI  - Mast cell-nerve interaction in the colon of Trypanosoma cruzi-infected
      individuals with chagasic megacolon.
AB  - Chagas disease is an infection caused by the parasite Trypanosoma cruzi that
      affects millions of people worldwide and is endemic in Latin America. Megacolon
      is the most frequent complication of the digestive chronic form and happens due
      to lesions of the enteric nervous system. The neuronal lesions seem to initiate
      in the acute phase and persist during the chronic phase, albeit the mechanisms
      involved in this process are still debated. Among the cells of the immune system
      possibly involved in this pathological process is the mast cell (MC) due to its
      well-known role in the bi-directional communication between the immune and
      nervous systems. Using ultrastructural analysis, we found an increased number of
      degranulated MCs in close proximity to nerve fibers in infected patients when
      compared with uninfected controls. We also immunostained MCs for the two pro
      inflammatory molecules tryptase and chymase, the first being also important in
      neuronal death. The number of MCs immunostained for tryptase or chymase was
      increased in patients with megacolon, whereas increased tryptase staining was
      additionally observed in patients without megacolon. Moreover, we detected the
      expression of the tryptase receptor PAR2 in neurons of the enteric nervous
      system, which correlated to the tryptase staining results. Altogether, the data
      presented herein point to the participation of MCs on the denervation process
      that occurs in the development of T. cruzi-induced megacolon.

PMID- 29470712
TI  - Diversity of Mammomonogamus (Nematoda: Syngamidae) in large African herbivores.
AB  - Four species of Mammomonogamus are known from large African herbivores. A recent
      study demonstrated that a single Mammomonogamus species was shared by both
      western lowland gorillas (Gorilla gorilla gorilla) and African forest elephants
      (Loxodonta cyclotis) in Central African Republic, suggesting lower species
      diversity than previously described in literature. We examined more than 500
      fecal samples collected from sympatric African forest elephants, western lowland
      gorillas, and African forest buffaloes (Syncerus caffer nanus) at four study
      sites across Central Africa and examined them by coproscopic methods to detect
      Mammomonogamus eggs, which were found at three of the study sites. Subsequently,
      sequences of 18S rDNA, 28S rDNA, and cox1 amplified from individual eggs were
      analyzed. Phylogenetic analyses of both nuclear and mitochondrial DNA revealed
      two clades: one formed by sequences originating from Gabonese buffaloes and the
      other comprising gorillas and elephants. The gorilla-elephant clade was further
      differentiated depending on the locality. We show the existence of at least two
      distinct species of Mammomonogamus, M. loxodontis in elephants and gorillas and
      M. nasicola in buffaloes. The available information on Mammomonogamus in African
      herbivores is reviewed.

PMID- 29470714
TI  - Surgical management of cauda syndrome in third trimester of pregnancy focusing on
      spinal anesthesia and right lateral positioning during surgery as possible
      practices.
AB  - PURPOSE: This article presents a surgical solution of a lumbar disc hernia of a
      pregnant woman focusing on the use of right lateral positioning, spinal
      anesthesia which has not previously been utilized in third trimester and
      discusses positioning options, and possible anesthesia methods with the surgical
      procedure options. METHODS: Case report. RESULTS: A left-sided L5/S1 lumbar disc
      hernia (verified by magnetic resonance imaging) of a 35-year-old, 32-week
      pregnant woman with a deteriorating neurological status leading to cauda syndrome
      was treated successfully by microdiscectomy in right lateral position applying
      spinal anesthesia. CONCLUSIONS: So far examples are given for almost every
      possible patient position in the third trimester except the right lateral one.
      All the previously presented positionings (prone, left lateral) were equally
      effective regarding the outcome with none being better than another. For left
      sided lumbar pathologies performed in the third trimester the right lateral
      position might be an alternative option for easier access. Based on the
      literature an epidural and general anesthesia can be applied successfully in the
      third trimester. Spinal anesthesia might be another anesthesia consideration.

PMID- 29470715
TI  - ISSLS PRIZE IN BIOENGINEERING SCIENCE 2018: dynamic imaging of degenerative
      spondylolisthesis reveals mid-range dynamic lumbar instability not evident on
      static clinical radiographs.
AB  - PURPOSE: Degenerative spondylolisthesis (DS) in the setting of symptomatic lumbar
      spinal stenosis is commonly treated with spinal fusion in addition to
      decompression with laminectomy. However, recent studies have shown similar
      clinical outcomes after decompression alone, suggesting that a subset of DS
      patients may not require spinal fusion. Identification of dynamic instability
      could prove useful for predicting which patients are at higher risk of post
      laminectomy destabilization necessitating fusion. The goal of this study was to
      determine if static clinical radiographs adequately characterize dynamic
      instability in patients with lumbar degenerative spondylolisthesis (DS) and to
      compare the rotational and translational kinematics in vivo during continuous
      dynamic flexion activity in DS versus asymptomatic age-matched controls. METHODS:
      Seven patients with symptomatic single level lumbar DS (6 M, 1 F; 66 +/- 5.0
      years) and seven age-matched asymptomatic controls (5 M, 2 F age 63.9 +/- 6.4
      years) underwent biplane radiographic imaging during continuous torso flexion. A
      volumetric model-based tracking system was used to track each vertebra in the
      radiographic images using subject-specific 3D bone models from high-resolution
      computed tomography (CT). In vivo continuous dynamic sagittal rotation
      (flexion/extension) and AP translation (slip) were calculated and compared to
      clinical measures of intervertebral flexion/extension and AP translation obtained
      from standard lateral flexion/extension radiographs. RESULTS: Static clinical
      radiographs underestimate the degree of AP translation seen on dynamic in vivo
      imaging (1.0 vs 3.1 mm; p = 0.03). DS patients demonstrated three primary motion
      patterns compared to a single kinematic pattern in asymptomatic controls when
      analyzing continuous dynamic in vivo imaging. 3/7 (42%) of patients with DS
      demonstrated aberrant mid-range motion. CONCLUSION: Continuous in vivo dynamic
      imaging in DS reveals a spectrum of aberrant motion with significantly greater
      kinematic heterogeneity than previously realized that is not readily seen on
      current clinical imaging. LEVEL OF EVIDENCE: Level V data These slides can be
      retrieved under Electronic Supplementary Material.

PMID- 29470716
TI  - Denosumab: a potential treatment option for aneurysmal bone cyst of the atlas.
AB  - PURPOSE: Aneurysmal bone cysts (ABCs) of spine are conventionally treated with en
      bloc resection or intralesional excision/curettage and reconstruction or filling
      of defects with bone cement. For the treatment of upper cervical ABCs, en-bloc
      resections are often not desirable considering the risk/benefit ratio while the
      risk of recurrence after intralesional excision is high. Hence, alternative
      management options are often necessary. We describe our clinical experience with
      one such treatment alternative-denosumab for the treatment of ABC of Atlas.
      METHODS AND RESULTS: We present a case of 16-year-old boy who presented with neck
      pain and restriction of neck movements. A large lytic lesion with multiple fluid
      fluid interfaces involving vertebral arch of atlas was identified on further
      imaging. There was destruction of right lateral mass and the lesion was found
      encasing the right vertebral artery. Core needle biopsy confirmed the diagnosis
      of ABC. With no visible CT response after first session of intra-lesional
      injection of Calcitonin and Methylprednisolone, the patient was treated with
      denosumab (120 mg SC once-a-month) for a period of 12 months. His symptoms
      resolved within 7 months of onset of treatment and serial CT scans over 12-month
      treatment period showed complete ossification of the lesion. Further there was no
      evidence of recurrence at 12 months after completion of treatment. CONCLUSION:
      Our case report contributes to the accruing evidence on the effectiveness of
      denosumab for the treatment of spinal ABCs. However, long-term safety, risk of
      recurrence, optimal duration of treatment and consistency of denosumab are yet to
      be determined.

PMID- 29470717
TI  - Risk of central nervous system defects in offspring of women with and without
      mental illness.
AB  - We sought to determine the relationship between maternal mental illness and the
      risk of having an infant with a central nervous system defect. We analyzed a
      cohort of 654,882 women aged less than 20 years between 1989 and 2013 who later
      delivered a live born infant in any hospital in Quebec, Canada. The primary
      exposure was mental illness during pregnancy or hospitalization for mental
      illness before pregnancy. The outcomes were neural and non-neural tube defects of
      the central nervous system in any offspring. We computed risk ratios (RR) and 95%
      confidence intervals (CI) for the association between mental disorders and risk
      of central nervous system defects in log-binomial regression models adjusted for
      age at delivery, total parity, comorbidity, socioeconomic deprivation, place of
      residence, and time period. Maternal mental illness was associated with an
      increased risk of nervous system defects in offspring (RR 1.76, 95% CI 1.64
      1.89). Hospitalization for any mental disorder was more strongly associated with
      non-neural tube (RR 1.84, 95% CI 1.71-1.99) than neural tube defects (RR 1.31,
      95% CI 1.08-1.59). Women at greater risk of nervous system defects in offspring
      tended to be diagnosed with multiple mental disorders, have more than one
      hospitalization for mental disease, or be 17 or older at first hospitalization. A
      history of mental illness is associated with central nervous system defects in
      offspring. Women hospitalized for mental illness may merit counseling at first
      symptoms to prevent central nervous system defects at pregnancy.

PMID- 29470718
TI  - Prediction of Human Pharmacokinetics of Ulixertinib, a Novel ERK1/2 Inhibitor
      from Mice, Rats, and Dogs Pharmacokinetics.
AB  - BACKGROUND AND OBJECTIVES: Ulixertinib (BVD-523) is a novel and selective
      reversible inhibitor of ERK1/ERK2. The primary objectives of the study were to
      evaluate the pharmacokinetics of ulixertinib in mice, rats, and dogs followed by
      prediction of human pharmacokinetic profile by allometric equations with/without
      correction factors. METHODS: Oral and intravenous pharmacokinetic profiles of
      ulixertinib were generated in mice, rats, and dogs. The human intravenous
      pharmacokinetics profiles [volume of distribution (Vss) and clearance (CL)] were
      predicted employing simple allometry and using correction factors [maximum life
      span potential (MLP) and brain weight (BW)]. Pharmacokinetic data obtained from
      dogs were used to simulate human oral profile [area under the curve (AUC) and
      maximum plasma concentrations (Cmax)]. RESULTS: Post-intravenous administration
      the CL was moderate in dogs (15.5 mL/min/kg) and low in mice (6.24 mL/min/kg) and
      rats (1.67 mL/min/kg). Vss was 0.56, 0.36, and 1.61 L/kg in mice, rats, and dogs,
      respectively. The half-life (t1/2) of ulixertinib ranged between 1.0 and 2.5 h
      across the animal species. Following oral administration ulixertinib attained
      maximum concentration in plasma (Tmax) within 0.50-0.75 h in mice and rats,
      indicating that absorption was rapid; however, in dogs, Tmax attained at 2 h.
      Absolute oral bioavailability in mice and rats was > 92%; however, in dogs, it
      was 34%. By different allometric approaches, simple method and brain weight
      correction factor shown clear improvement in the prediction efficiency of
      allometric scaling for Vss (1.34-1.70 L/kg) and CL (4.18-6.09 mL/min/kg),
      respectively, comparing with the MLP method and simple method for CL. Similarly,
      simulation of oral human profile was attained from scaled values and dog data to
      predict reported human profile (AUC and Cmax). CONCLUSIONS: The derived
      pharmacokinetic parameters (AUC and Cmax at 600 mg dose) and simulated plasma
      concentration-time profiles of ulixertinib in humans were predicted with good
      confidence by allometric approach.

PMID- 29470719
TI  - Seasonal and spatial variation of reservoir water quality in the southwest of
      Ethiopia.
AB  - This research investigated the spatiotemporal variation of water quality in the
      Gilgel Gibe reservoir, Ethiopia, using physicochemical water quality parameters.
      Nonparametric tests and multivariate statistical techniques were used to evaluate
      data sets measured during dry and rainy seasons. Electrical conductivity (EC),
      pH, biochemical oxygen demand (BOD5), total phosphorus (TP), total nitrogen (TN),
      nitrate (NO3-), total dissolved solids (TDSs), and total suspended solids (TSSs)
      were all significantly different among seasons (Mann-Whitney U test, p < 0.01).
      In addition, principal component analysis distinguished dry season samples from
      wet season samples. The dry season was positively associated with EC, pH, TP, TN,
      NO3-, TDS, and TSS and negatively associated with BOD5. The wet season was in
      contrast associated with high values of turbidity, soluble reactive phosphorus
      (SRP), water temperature, and dissolved oxygen (DO). Within the reservoir,
      spatial variation was observed for some of the water quality parameters, with
      significant difference at p = < 0.05. Overall, high nutrient concentrations
      suggest eutrophic conditions, likely due to high nutrient loading from the
      watershed. Levels of TSS, attributed to inputs from tributaries, have been
      excessive enough to inhibit light penetration and thus have a considerable impact
      on the aquatic food web. Our findings indicate that the reservoir is at high risk
      of eutrophication and siltation, and hence, urgent action should target the
      planning and implementation of integrated watershed management for this and
      similar reservoirs in the region.

PMID- 29470721
TI  - Association of ischemic stroke with ankylosing spondylitis: a nationwide
      longitudinal cohort study.
AB  - BACKGROUND: The purpose of this nationwide age- and sex-matched longitudinal
      follow-up study was to investigate the risk of developing ischemic stroke in
      ankylosing spondylitis (AS). METHODS: The data in this study, spanning from
      January 1, 2010 to December 31, 2014, was obtained from a database maintained by
      the Korean National Health Insurance Service. A total of 12,988 patients with a
      diagnosis of AS were enrolled. The control group consisted of 64,940 age-sex
      stratified matching subjects without AS. The 6year ischemic stroke incidence rate
      for each group was calculated using the Kaplan-Meier method. Cox proportional
      hazards regression analysis was used to estimate the hazard ratio of ischemic
      stroke. RESULTS: During the follow-up period, 73 patients (0.56%) in the AS group
      and 250 patients (0.38%) in the control group developed ischemic stroke (p =
      0.0041). The hazard ratio of ischemic stroke in the AS group was 1.46 (95%
      confidence interval [95% CI], 1.13-1.90) after adjusting for age and sex. The
      adjusted hazard ratio of ischemic stroke in the AS group was 1.35 (95% CI, 1.04
      1.75) after controlling for demographics and comorbid medical disorders.
      According to subgroup analysis, in female and diabetes and non-hypertension and
      dyslipidemia subgroups, ischemic stroke incidence rates were significantly higher
      in AS patients than those in control group. CONCLUSION: Our nationwide
      longitudinal study suggests an increased risk of ischemic stroke in AS patients.

PMID- 29470720
TI  - Diagnostic Tools for Inborn Errors of Human Immunity (Primary Immunodeficiencies
      and Immune Dysregulatory Diseases).
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an overview of
      diagnostic testing in primary immunodeficiency and immune dysregulatory disorders
      (PIDDs), particularly focusing on flow cytometry and genetic techniques,
      utilizing specific examples of PIDDs. RECENT FINDINGS: Flow cytometry remains a
      vital tool in the diagnosis and monitoring of immunological diseases. Its utility
      ranges from cellular analysis and specific protein quantitation to functional
      assays and signaling pathway analysis. Mass cytometry combines flow cytometry and
      mass spectrometry to dramatically increase the throughput of multivariate single
      cell analysis. Next-generation sequencing in combination with other molecular
      techniques and processing algorithms has become more widely available and
      identified the diverse and heterogeneous genetic underpinnings of these
      disorders. As the spectrum of disease is further clarified by increasing
      immunological, genetic, and epigenetic knowledge, the careful application of
      these diagnostic tools and bioinformatics will assist not only in our
      understanding of these complex disorders, but also enable the implementation of
      personalized therapeutic approaches for disease management.

PMID- 29470722
TI  - Can anodised zirconium implants stimulate bone formation? Preliminary study in
      rat model.
AB  - The mechanical properties and good biocompatibility of zirconium and some of its
      alloys make these materials good candidates for biomedical applications. The
      attractive in vivo performance of zirconium is mainly due to the presence of a
      protective oxide layer. In this preliminary study, the surface of pure zirconium
      modified by anodisation in acidic media at low potentials to enhance its barrier
      protection given by the oxides and osseointegration. Bare, commercially pure
      zirconium cylinders were compared to samples anodised at 30 V through
      electrochemical tests and scanning electron microscopy (SEM). For both
      conditions, in vivo tests were performed in a rat tibial osteotomy model. The
      histological features and fluorochrome-labelling changes of newly bone formed
      around the implants were evaluated on the non-decalcified sections 63 days after
      surgery. Electrochemical tests and SEM images show that the anodisation treatment
      increases the barrier effect over the material and the in vivo tests show
      continuous newly formed bone around the implant with a different amount of
      osteocytes in their lacunae depending on the region. There was no significant
      change in bone thickness around either kind of implant but the anodised samples
      had a significantly higher mineral apposition, suggesting that the anodisation
      treatment stimulates and assists the osseointegration process. We conclude that
      anodisation treatment at 30 V can stimulate the implant fixation in a rat model,
      making zirconium a strong candidate material for permanent implants.

PMID- 29470723
TI  - Cyclin-dependent kinase 4/6 inhibitors as first-line treatment for post
      menopausal metastatic hormone receptor-positive breast cancer patients: a
      systematic review and meta-analysis of phase III randomized clinical trials.
AB  - BACKGROUND: To compare the efficacy and toxicity of the combination of cyclin
      dependent kinase 4/6 (CDK 4/6) inhibitors and nonsteroidal aromatase inhibitors
      (AI) versus AI alone as first-line therapy for patients with advanced hormone
      receptor-positive breast cancer. MATERIALS AND METHODS: Phase III randomized
      clinical trials (RCT) were identified after a systematic review of electronic
      databases. A random-effect model was used to determine the pooled hazard ratio
      (HR) for progression-free survival (PFS) using the inverse-variance method. The
      Mantel-Haenszel method was used to calculate the pooled odds ratio (OR) for
      overall response, clinical benefit rate and treatment-related side effects.
      Heterogeneity was measured using the tau-squared and I2 statistics. RESULTS:
      After a systematic search, three phase III RCT (n = 1827) were included. The use
      of CDK 4/6 inhibitors (abemaciclib, palbociclib, and ribociclib) in combination
      with an AI was significantly associated with longer PFS compared to the use of
      letrozole or anastrozole alone (HR: 0.57; 95% CI 0.50-0.65; p < 0.00001), with no
      significant heterogeneity among trials. Similarly, overall response rate and
      clinical benefit rate were higher for patients who received the combination
      therapy than for patients allocated to AI alone. Grade 3 or higher treatment
      related side effects were more frequently reported for patients who received CDK
      4/6 inhibitors (OR: 7.51; 95% CI 6.01-9.38; p < 0.00001), these included mainly
      neutropenia, leukopenia and anemia. CONCLUSION: The addition of CDK 4/6
      inhibitors (either abemaciclib, palbociclib, or ribociclib) to an AI (anastrozole
      or letrozole) significantly improved PFS, overall response rate, and clinical
      benefit rate in comparison with a nonsteroidal AI alone.

PMID- 29470724
TI  - Physico-chemical characteristics of gamma-irradiated gelatin.
AB  - This article reports the effects of gamma irradiation (dose ranges 0.1-10 kGy
      from 60Co source) on the characteristics of solid gelatin and the physico
      mechanical, microstructural and bioactive properties of the scaffold prepared
      from irradiated gelatin solution. FTIR, intrinsic viscosity, bloom strength,
      thermal properties, SEM, tensile properties, water uptake ability and
      antimicrobial activities of non-irradiated and irradiated solid gelatin and its
      scaffolds were investigated. The detailed experimental results for the solid
      gelatin demonstrated that 1 kGy gamma-irradiated samples showed higher intrinsic
      viscosity, enhanced thermal stability and bloom strength than other irradiated
      samples. Furthermore, the scaffold thus prepared from irradiated and non
      irradiated gelatin also revealed that 1 kGy samples showed the highest tensile
      strength and modulus with good water resistivity than other irradiated and non
      irradiated samples. In addition to the physico-mechanical properties, 1 kGy
      scaffolds have also exhibited the highest resistivity towards microbial growth
      that can have potentiality as scaffold in biomedical sector. The enhanced
      functional and bioactive properties at low irradiation doses (1 kGy) may occurred
      due to an initial breaking of hydrogen bonds of polypeptide chains in gelatin
      molecules that indicated by the shift of amide A, I and II peaks to higher wave
      numbers in FTIR. This enhancement resulted probably due to the domination of
      crosslinking over degradation at 1 kGy. It was also observed that 1 kGy gamma
      radiation-induced crosslinking has lowered the hydrophilicity by decreasing water
      uptake and mean pore diameter of the interconnected porous structures of gelatin.

PMID- 29470725
TI  - Recent advances in therapeutic strategies for unresectable or metastatic melanoma
      and real-world data in Japan.
AB  - New therapeutic strategies including immunotherapy and selective molecular target
      inhibitors have brought about a new era in the treatment of patients with
      advanced melanoma. In Japan, the immune checkpoint inhibitors ipilimumab,
      nivolumab and pembrolizumab, the BRAF inhibitor (BRAFi) vemurafenib, dabrafenib
      and MEK inhibitor (MEKi) trametinib have been available for the treatment of
      unresectable and metastatic melanoma. The BRAFi + MEKi combination shows high
      response rates (60-70%) and rapid response induction associated with symptom
      control, with a progression-free survival of 12 months. Nivolumab and
      pembrolizumab offer moderate response rates (30-40%) and long survival (3- to 5
      year survival: 30-50%). In Japan, treatment options for the first-line setting
      frequently include nivolumab or pembrolizumab monotherapy and BRAFi + MEKi
      combinations (for patients with BRAF-mutant melanoma). Ipilimumab is included in
      the second-line setting, and the nivolumab + ipilimumab combination has not been
      approved yet in Japan. Although these medications have demonstrated impressive
      efficacy, the clinical trials and real-world data have shown that the clinical
      benefit is not fully satisfactory. We have to carefully manage a new class of
      adverse events due to these medicines. Moreover, biomarkers are emerging with
      which we can identify a population that would experience more benefits without
      severe adverse events.

PMID- 29470726
TI  - Polystyrene surface modification using excimer laser and radio-frequency plasma:
      blood compatibility evaluations.
AB  - Biomaterial surface modification is an efficient method to improve and control
      blood component-material interactions. In the present study, two different
      methods (ArF excimer laser irradiation and radio-frequency (RF) plasma treatment)
      were applied in separate procedures to create a vast range of physicochemical
      characteristics on the surface of polystyrene (PS) and investigate their effects
      on blood compatibility of treated surfaces. Atomic force microscopy (AFM) and
      Fourier transmission infrared analysis were applied to study the morphology and
      chemical characteristics of treated samples in comparison with those of the
      untreated PS. Contact angle and surface tension measurements with two different
      solvents were used to evaluate the wettability and surface energy of the treated
      PS films. The effect of the physicochemical properties of the PS surface on blood
      compatibility was investigated using lactate dehydrogenase (LDH) method. AFM
      studies showed that after laser treatment, some distinctive nanostructures are
      created on the surface of PS. The data from contact angle measurements
      demonstrated that ArF excimer laser irradiation and RF plasma treatment created
      surfaces with a vast range of properties in the wettability point of view. The
      LDH results revealed that after surface modification by laser irradiation and
      plasma treatment, blood compatibility of PS films was enhanced. In addition,
      these results offered that the most blood compatible samples were those which
      irradiated with 5 pulses of laser and the one treated 4 minutes in oxygen plasma.

PMID- 29470727
TI  - pH-responsive stealth micelles composed of cholesterol-modified PLA as a nano
      carrier for controlled drug release.
AB  - Present research is a preliminary report on the novel pH-responsive micelles
      based on an amphiphilic brush copolymer P(PEGMA)-b-P(DMAEMA-co-CPLAMA) used as
      the promising drug carrier. The copolymer was synthesized using cholesteryl
      poly(L-lactic acid) methacrylate (CPLAMA), poly(ethylene glycol) monomethyl ether
      methacrylate (PEGMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) with
      appropriate hydrophobic/hydrophilic ratios via atom transfer radical
      polymerization. The copolymer compositions were determined by 1H NMR. The
      synthesized copolymer self-assembled into nano-scale micelles capable of
      encapsulating hydrophobic model drug naproxen in their hydrophobic cores in
      aqueous solutions. pH sensitivity and self-assembly behaviors of copolymer were
      studied by UV-vis transmittance, fluorescence spectroscopy, transmission electron
      microscopy (TEM) and dynamic light scattering. The results showed that the
      copolymer had high pH responsivity with a phase transition pH around pH 6.2. The
      critical micelle concentrations at pH 6.5 were found about 2.4 mg L-1. The stable
      and small micelles were obtained at pH 5.5-6.5. Upon increasing pH higher than 7,
      the single micelles further assembled into the micellar aggregates. TEM images of
      copolymer micelles showed that the micelles are spherical in shape with the mean
      diameter of 152 nm at pH 6.2. In vitro release study of naproxen-loaded micelles
      with about 44 % loading efficiency and 8 % loading capacity was performed using
      dialysis method in phosphate-buffered solution at 37  degrees C. Release study
      implied that the proposed brush copolymer could produce stable nano-carriers with
      controllable drug release at the target sites (pH 5.5-7).

PMID- 29470728
TI  - Fecal incontinence after transanal endoscopic microsurgery.
AB  - PURPOSE: Transanal endoscopic microsurgery (TEM) procedure could potentially
      influence the development of fecal incontinence later in life. The aim of our
      study was to assess long-term functional outcomes after TEM and to determine
      possible variables related to incontinence. METHODS: Patients, enrolled in a
      prospectively collected TEM operation database, were interviewed using a postal
      questionnaire. The questionnaire consisted of EuroQol (EQ)-5D-5L quality of life
      questionnaire, Wexner fecal incontinence grading scale, and additional questions
      about other perianal operations and obstetric history for women. We divided
      patients into two groups: no or minor fecal incontinence (Wexner score of 2 and
      less) and non-minor incontinence (Wexner score of 3 or more). RESULTS: One
      hundred thirty-two patients were included in the study. Patients' median follow
      up time was 96 (12-168) months from their operation. Thirty-eight patients
      (28.8%) reported Wexner score of 3 or more, and they reported significantly worse
      quality of life in all tested life spheres. They were older at the time of the
      operation (63 (18-82) vs. 68 (50-89) years; p = 0.004), underwent longer
      operations (50 (10-140) vs. 60 (15-210) min; p = 0.017), and more often were
      operated for malignant lesions (17 (18.3%) vs. 14 (36.8%); p = 0.040). Older age
      at the time of operation was an independent risk factor in multivariate model (OR
      1.057, 95% CI 1.010-1.106; p = 0.016). CONCLUSIONS: Fecal incontinence after TEM
      is more common than thought previously, resulting in significantly impaired
      quality of life. Older age at the time of operation was an independent risk
      factor for developing significant fecal incontinence.

PMID- 29470729
TI  - Retromesenteric course of the middle colic artery-challenges and pitfalls in D3
      right colectomy for cancer.
AB  - BACKGROUND: The middle colic artery (MCA) is of crucial importance in abdominal
      surgery, for laparoscopic or open right and transverse colectomies. Against this
      background, a high number of reports concerning anatomical variations of the MCA
      have been published intended to contribute to the improvement of operative
      techniques for the treatment of colon cancer. Despite this extensive literature,
      briefly reviewed in the present paper, a course of the MCA posterior to the
      superior mesenteric vein, called a retromesenteric trajectory, has been related
      to only once, to the best of our knowledge. METHODS: A total series of 507
      patients included in two prospective trials concerning laparoscopic or open right
      colectomy for cancer between 2011 and 2017 are reported. The investigation
      included preoperative or postoperative multidetector-computed tomography
      angiography. RESULTS: We found four (0.79%) cases of retromesenteric MCA. They
      all underwent meticulous image analysis with mesenteric vessels' road mapping,
      detailed morphometry, and surgical validation which revealed that, apart from
      their course, those cases did not differ significantly from the rest of the
      series. CONCLUSION: This paper therefore documents the worth-knowing behavior
      causing considerable confusion for the operating surgeon unaware of the
      abnormality and shows its concrete impact on patient-tailored surgical practice,
      in particular for laparoscopic D3 colectomy (including the "uncinated process
      first" approach).

PMID- 29470730
TI  - Sacral nerve stimulation versus percutaneous tibial nerve stimulation for faecal
      incontinence: a systematic review and meta-analysis.
AB  - AIMS: Percutaneous tibial nerve stimulation (PTNS) and sacral nerve stimulation
      (SNS) are both second-line treatments for faecal incontinence (FI). To compare
      the clinical outcomes and effectiveness of SNS versus PTNS for treating FI in
      adults. METHOD: A literature search of MEDLINE, Embase, Science Citation Index
      Expanded and Cochrane was performed in order to identify studies comparing SNS
      and PTNS for treating FI. A risk of bias assessment was performed using The
      Cochrane Collaboration's risk of bias tool. A random effects model was used for
      the meta-analysis. RESULTS: Four studies (one randomised controlled trial and
      three nonrandomised prospective studies) reported on 302 patients: 109 underwent
      SNS and 193 underwent PTNS. All included studies noted an improvement in symptoms
      after treatment, without any significant difference in efficacy between SNS and
      PTNS. Meta-analysis demonstrated that the Wexner score improved significantly
      with SNS compared to PTNS (weighted mean difference 2.27; 95% confidence interval
      3.42, 1.12; P < 0.01). Moreover, SNS was also associated with a significant
      reduction in FI episodes per week and a greater improvement in the Fecal
      Incontinence Quality of Life coping and depression domains, compared to PTNS on
      short-term follow-up. Only two studies reported on adverse events, reporting no
      serious adverse events with neither SNS nor PTNS. CONCLUSION: Current evidence
      suggests that SNS results in significantly improved functional outcomes and
      quality of life compared to PTNS. No serious adverse events were identified with
      either treatment. Further, high-quality, multi-centre randomised controlled
      trials with standardised outcome measures and long-term follow-up are required in
      this field.

PMID- 29470732
TI  - Thermal, mechanical, and moisture absorption properties of egg white protein
      bioplastics with natural rubber and glycerol.
AB  - Petroleum-based plastics have many drawbacks: the large amount of energy required
      to produce the plastic, the waste generated as a result of plastic production,
      and the accumulation of waste due to slow degradation rate. It is because of
      these negative attributes of conventional plastic use that attention is being
      focused on environmentally friendly plastics from alternative sources. Albumin
      protein provides one possible source of raw material, with inherent antimicrobial
      properties that may make it suitable for medical applications. We conducted this
      study to investigate the various bioplastic properties of the albumin with the
      use of three plasticizers - water, glycerol, and natural rubber latex. Based on
      results, 75:25 albumin-water, 75:25 albumin-glycerol, and 80:20 albumin-natural
      rubber were the best blending ratios for each plasticizer for a subsequent time
      study to determine water stability, with the 80:20 albumin-natural rubber blend
      ratio having possessed the best thermal, tensile, and viscoelastic properties
      overall.

PMID- 29470731
TI  - Sacral neuromodulation versus personalized conservative treatment in patients
      with idiopathic slow-transit constipation: study protocol of the No.2-trial, a
      multicenter open-label randomized controlled trial and cost-effectiveness
      analysis.
AB  - PURPOSE: The evidence regarding the (cost-)effectiveness of sacral
      neuromodulation (SNM) in patients with therapy-resistant idiopathic slow-transit
      constipation is of suboptimal quality. The Dutch Ministry of Health, Welfare and
      Sports has granted conditional reimbursement for SNM treatment. The objective is
      to assess the effectiveness, cost-effectiveness, and budget impact of SNM
      compared to personalized conservative treatment (PCT) in patients with idiopathic
      slow-transit constipation refractory to conservative treatment. METHODS: This
      study is an open-label, multicenter randomized controlled trial. Patients aged 14
      to 80 with slow-transit constipation, a defecation frequency (DF) < 3 per week
      and meeting at least one other Rome-IV criterion, are eligible. Patients with
      obstructed outlet, irritable bowel syndrome, bowel pathology, or rectal prolapse
      are excluded. Patients are randomized to SNM or PCT. The primary outcome is
      success at 6 months (DF >= 3 a week), requiring a sample size of 64 (alpha =
      0.05, beta = 0.80, 30% difference in success). Secondary outcomes are straining,
      sense of incomplete evacuation, constipation severity, fatigue, constipation
      specific and generic quality of life, and costs at 6 months. Long-term costs and
      effectiveness will be estimated by a decision analytic model. The time frame is
      57 months, starting October 2016. SNM treatment costs are funded by the Dutch
      conditional reimbursement program, research costs by Medtronic. CONCLUSIONS: The
      results of this trial will be used to make a final decision regarding
      reimbursement of SNM from the Dutch Health Care Package in this patient group.
      TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov , identifier
      NCT02961582, on 12 October 2016.

PMID- 29470733
TI  - Optimization of monomethoxy poly(ethylene glycol) grafting on Langerhans islets
      capsule using response surface method.
AB  - Langerhans islet transplantation is a much less invasive approach compared with
      the pancreas transplantation to 'cure' diabetes. However, destruction of
      transplanted islets by the immune system is an impediment for a successful
      treatment. Chemical grafting of monomethoxy poly(ethylene glycol) onto pancreatic
      islet capsule is a novel approach in islet immunoisolation. The aim of this study
      was to determine an optimized condition for grafting of monomethoxy poly(ethylene
      glycol) succinimidyl propionate (mPEG-SPA) on islets capsule. Independent
      variables such as reaction time, the percentage of longer mPEG in the mixture,
      and polymer concentration were optimized using a three-factor, three-level Box
      Behnken statistical design. The dependent variable was IL-2 (interleukin-2)
      secretion of lymphocytes co-cultured with PEGylated or uncoated control islets
      for 7 days co-culturing. A mathematical relationship is obtained which explained
      the main and quadratic effects and the interaction of factors which affected IL-2
      secretion. Response surface methodology predicted the optimized values of
      reaction time, the percentage of longer mPEG in the mixture, and polymer
      concentration of 60 min to be 63.7% mPEG10 and 22 mg/mL, respectively, for the
      minimization of the secreted IL-2 as response. Islets which were PEGylated at
      this condition were transplanted to diabetic rats. The modified islets could
      survive for 24 days without the aid of any immunosuppressive drugs and it is the
      longest survival date reported so far. However, free islets (unmodified islets as
      control) are completely destroyed within 7 days. These results strongly suggest
      that this new protocol provides an effective clinical means of decreasing
      transplanted islet immunogenicity.

PMID- 29470734
TI  - Characterization of a novel nanobiomaterial fabricated from HA, TiO2 and Al2O3
      powders: an in vitro study.
AB  - For the purposes of this study, hydroxyapatite (HA)-Al2O3-TiO2 nanobiomaterial
      with significant surface properties and biocompatibility capable of forming
      surface apatite was fabricated by cold-press and sintering method. Samples were
      examined for hardness and porosity. The results showed that in terms of hardness
      and porosity, sample A (50 wt% TiO2-30 wt% HA-20 wt% Al2O3) was superior to
      sample B (30 wt% TiO2-50 wt% HA-20 wt% Al2O3), and also the density of
      nanobiomaterial was close to natural bone density. Bioactivity of the samples in
      a simulated body fluid (SBF) was investigated. Then, after immersing the samples
      in SBF solution for a period of 7 days, sample B exhibited greater ability to
      form calcium phosphate compounds on the surface as compared to sample A. In
      addition, in vitro studies showed that MG-67 osteoblast-like cells attached and
      spread on the samples surface. The results showed that cells proliferated in
      greater numbers on the sample B as compared to the sample A. Finally, X-ray
      diffraction, scanning electron microscopy, and energy-dispersive X-ray analysis
      were performed to identify phases, study microstructure, and determine percentage
      of elements, respectively. The results revealed that considering their different
      properties, both nanobiomaterials can be used in medical applications.

PMID- 29470735
TI  - The influence of different sterilization types on mosquito net mesh
      characteristics in groin hernia repair.
AB  - BACKGROUND: In low-resource countries, a suture repair is still in common use due
      to the limited access to commercial mesh implants. The search for less expensive
      alternatives to the synthetic meshes has led to using mosquito nets. Sterilized
      mosquito net appears to be a low-cost and commonly available product that closely
      resembles commercially available meshes. However, the extent to which
      sterilization alters the structure of mosquito nets is still unknown. The aim of
      this research was to assess the effects of different sterilization types on
      physico-mechanical properties of mosquito nets. MATERIALS AND METHODS: Nine
      different polymers were analyzed (six mosquito nets from low-resource countries,
      one European net, and two commercial meshes). The analyzed parameters included:
      polymer type, net surface area, fiber diameter, net thickness, mesh weight, pore
      size, tensile strength, and tear force. The measurements were taken before
      sterilization, after sterilization at 121 and at 134  degrees C. RESULTS:
      Sterilization altered net surface and pore size, but did not significantly alter
      the single fiber diameter, weave of filaments, or net thickness. Steam
      sterilization did not affect the tensile strength or tear force. CONCLUSIONS: The
      reduction of the mosquito net surface area by more than 40% due to sterilization
      at 121  degrees C, results in a loss of macroporous structure, turning the mesh
      into hard, shrunken, non-pliable masses. Sterilization at 134  degrees C causes
      some mosquito nets to melt and completely destroys their porous structure.
      Maximum pressure in the abdominal cavity is higher than the tensile strength and
      tear force of some locally available mosquito nets; therefore, these nets should
      not be used.

PMID- 29470736
TI  - Correction to: Color stability of different composite resins after polishing.
AB  - In the original publication of the article, the author's name "Prof. Rene Daher"
      was inadvertently missed in the author group. This has been updated in this
      erratum. Also, the original article has been corrected.

PMID- 29470737
TI  - The safety of iloprost in systemic sclerosis in a real-life experience.
AB  - Iloprost (ILO) is employed intravenously for the treatment of severe Raynaud
      phenomenon (RP) and digital ulcers (DU) in systemic sclerosis (SSc). The aim of
      this study was to evaluate the safety and tolerability of the intravenous
      treatment with ILO in different phases of SSc. Eighty-one consecutive non
      selected SSc patients, all on nifedipine, with moderate RP, treated with ILO
      infusion, were retrospectively evaluated. Patients were sub classified according
      to the edematous or fibrotic/atrophic cutaneous phase of the disease. ILO was
      infused with a progressive increase of the dosage up to the achievement of
      patient's tolerance, 1 day/week. In cases of slower infusion regimen due to
      adverse events (AE) at the beginning of the administration, patients received a
      lower dose of the drug (not possible to quantify precisely the final cumulative
      dosage). 16/81 SSc patients presented digital edema, 5 developed diarrhea, and 9
      developed transient hypotension during the infusion at 20 ml/h that ameliorated
      when the drug was withdrawn. Moreover, 10/16 edematous patients experienced
      significant and painful digital swelling, unlike patients in the fibrotic group
      (p < 0.0001); 11/16 patients reported flushing and 7/16 headache, always
      controlled with dose tapering below 10 ml/h. In the atrophic/fibrotic phase
      patients (65/81), 10 developed diarrhea and 24 hypotension at infusion rate of 20
      ml/h that led to temporary withdrawal of the drug. When ILO was restarted and
      kept below 10 ml/h, no side effects were experienced. 23/65 patients experienced
      flushing and 8/65 headache, all controlled with infusion reduction below 10 ml/h.
      In these patients, adverse events were significantly less frequent than in the
      edematous group (p = 0.023 and p = 0.008, respectively). Our data suggest that
      calcium channel blockers should be transitorily stopped while using ILO and that
      a pre-treatment approach might reduce or control adverse events. In patients with
      digital edema, ILO infusion should be carefully employed after the evaluation of
      patient's drug tolerance.

PMID- 29470738
TI  - Prevalence and type II diabetes-associated factors in psoriatic arthritis.
AB  - Diabetes is a common cardiovascular risk factor in psoriatic arthritis (PsA).
      Although the prevalence of diabetes is high, the factors associated with it in
      PsA are poorly understood. We aimed to analyse the prevalence of type II diabetes
      and diabetes-associated factors in a hospital-based population with PsA. This
      cross-sectional study included 340 consecutive patients attended in a tertiary
      care hospital. The prevalence of diabetes was compared to that of 600 outpatients
      without inflammatory conditions. To analyse diabetes-associated factors, odds
      ratio (OR) values were calculated by conditional logistic regression analysis.
      Significant variables in the univariate analysis were then introduced in a
      multivariate analysis with a backward stepwise approach. Diabetes was more
      prevalent among PsA patients (13.8 vs. 5%, OR 2.8, 95% CI: 1.7-4.3, p < 0.0001).
      Diabetes-associated factors in the univariate analysis (p < 0.05) were the
      following: an age of onset of psoriasis > 40 years, an age of onset of arthritis
      > 40 years, a low educational level, family history of psoriasis, pustular
      psoriasis, high number of swollen joints during follow-up, hypertension,
      dyslipidemia, obesity, and cardiovascular events. After controlling for several
      confounders, diabetes was significantly associated with late-onset psoriasis (OR
      8.2, 95% CI: 1.9-12.4, p = 0.002) and hypertension (OR 7.5, 95% CI: 1.5-13.3, p =
      0.008). Diabetes risk should be carefully evaluated in patients with PsA whose
      psoriasis begins after 40 years.

PMID- 29470739
TI  - The association between osteoarthritis and sleep duration in Koreans: a
      nationwide cross-sectional observational study.
AB  - Osteoarthritis (OA) causes chronic pain, physical disability, and mental health
      deterioration and reduces the quality of life of patients. Sleep is an important
      factor in the recovery, and adequate sleep is important for quality of life.
      Several features of patients with OA can affect sleep time, and sleep also
      affects OA. We investigated the relationship between OA and sleep duration. Data
      for 2010-2012 were collected from the Korea National Health and Nutrition
      Examination Survey. We included 11,540 participants (4915 men and 6625 women).
      Patients with OA were defined as participants with knee/hip joint pain and
      radiographic changes of the knee/hip joints. Sleep time was divided into 4
      sections as follows: (1) 0-3 h, (2) 4-5 h, (3) 6-7 h, and (4) >= 8 h. Sleep time
      of 6 and 7 h was the most frequent and set as the reference time. In the multiple
      logistic regression model, the patients who slept for 0-3 and 4-5 h had odds
      ratios (ORs) of 2.28 (95% confidence interval [CI] 1.14-4.55) and 1.38 (95% CI
      1.01-1.89) for men and 1.63 (95% CI 1.19-2.24) and 1.26 (95% CI 1.08-1.47) for
      women, respectively, for having OA. The prevalence of OA was lowest in the
      participants who had 6-7 h of sleep and progressively increased with shorter
      sleep time. Thus, sleep duration was significantly associated with OA.

PMID- 29470740
TI  - Effect of supplementing germinated sprouts of pulses on performance, carcass
      variables, immune and oxidative stress indicators in broiler chickens reared
      during tropical summer season.
AB  - An experiment was conducted to study the effects of supplementing sprouts of
      pulses on performance, carcass variables, immune responses, and anti-oxidant
      variables in broiler chicken (day 1 to 6 weeks of age) reared during summer
      season in tropical region. Sprouts of black gram (BG, Vigna mungo), green gram
      (GG, Vigna radiata), and wild gram (WG, Vigna trilobata) were produced by soaking
      the pulses in water for 16 h and incubating at 37  degrees C for 24 h. Total
      phenolic content in sprouts of WG, BG, and GG was 102, 96.1, and 79.2 mg GAE/g,
      respectively, while the anti-radical activity in the sprouts was 61, 58, and 52%,
      respectively. A total of 200-day-old broiler male chicks were equally and
      randomly distributed in to 4 groups, each having 10 replicates of 5 chicks and
      housed in battery brooders in open-sided poultry house. Each of these groups was
      fed sprouts of BG, GG, or WG at 5% of feed intake, while the control group
      without feeding sprouts was kept for comparison. The trial was conducted during
      mid summer season (April and May, 2017). Feed conversion ratio (FCR) was reduced
      (P < 0.05) in broilers fed sprouted pulses compared to the control group at day
      21. However, the body weight gain and FCR at 42 days of age, slaughter variables,
      and immune responses were not affected due to feeding of sprouted pulses. Feeding
      of sprouts significantly (P < 0.05) reduced lipid peroxidation and increased (P <
      0.05) the activities of glutathione peroxidase, glutathione reductase, and
      superoxide dismutase in liver and spleen of broilers compared to the control
      group. Based on the results, it is concluded that oxidative stress in broiler
      chicken reared in tropical summer could be reduced by supplementing sprouted
      pulses without affecting performance, carcass variables, and immune responses.

PMID- 29470741
TI  - Electrospun eri silk fibroin scaffold coated with hydroxyapatite for bone tissue
      engineering applications.
AB  - Natural biomaterials such as collagen, silk fibroin, and chitosan, and synthetic
      biopolymers such as polylactic acid, polycaprolactone, polyglycolic acid, and
      their copolymers are being used as scaffold for tissue engineering applications.
      In the present work, a fibrous mat was electrospun from eri silk fibroin (ESF). A
      composite of hydroxyapatite (Hap) and the ESF scaffold was prepared by soaking
      the ESF scaffold in a solution of calcium chloride and then in sodium diammonium
      phosphate. The average tensile stress of the pure ESF and hydroxyapatite-coated
      ESF scaffold (ESF-Hap) was found to be 1.84 and 0.378 MPa, respectively. Pure ESF
      and ESF-Hap scaffolds were evaluated for their characteristics by a
      themogravimetric analyzer and Fourier transform infrared spectroscope. The
      crystallinity and thermal stability of the ESF-Hap scaffold were found to be more
      than that of uncoated eri silk nanofiber scaffold. The water uptake of the pure
      ESF and ESF-Hap scaffolds was found to be 69% and 340%, respectively, in
      distilled water as well as phosphate buffer saline. The hemolysis percentage of
      both scaffolds was less than 5%, which indicate their good blood compatibility.
      The cytocompatibility studied by 3-(4,5-dimethyl) thiazol-2-yl-2,5-dimethyl
      tetrazolium bromide assay showed that the scaffold is biocompatible. To assess
      cell attachment and growth on the scaffold, human mesenchymal stem cells were
      cultured on the scaffolds. The results from scanning electron microscopy and
      fluorescent microscopy showed a notable cellular growth and favorable
      morphological features. Hence, the ESF-Hap scaffold is better suited for cell
      growth than the pure ESF scaffold.

PMID- 29470742
TI  - Renal hemosiderosis with uncontrolled hypertension.

PMID- 29470744
TI  - Polystyrene microsphere and 5-fluorouracil release from custom-designed wound
      dressing films.
AB  - Custom-designed wound dressing films of chitosan and alginate have been prepared
      by a casting/solvent evaporation method for hydrophobic therapeutic agent
      encapsulation. In this parametric study, the propylene glycol (PG) and calcium
      chloride (CaCl2) concentrations were varied for chitosan and alginate films,
      respectively. Mechanical and chemical inter-related responses under observations
      included thickness (th), elasticity (E), tensile strength (TS), sorption ability
      (S%) and kinetics of in-vitro drug release, specifically in terms of membrane
      time to burst (t B ) and duration of release (t R ). As shown by results of a one
      tailed t-test significance testing at the 95% confidence interval (alpha = 0.05),
      alginate films were significantly more elastic (p = 0.003), thinner (p = 0.004)
      and more susceptible to osmotic burst (p = 0.011) and characterized by a longer
      duration of release (p = 0.03). Meanwhile chitosan films exhibited superior
      moisture permeability (p = 0.006) and sorption characteristics (p = 0.001),
      indicative of higher hydrophilicity. There were no significant differences in
      tensile strength (p = 0.324) for alginate and chitosan-based formulations.
      Preliminary testing was conducted using 0.71 MUm in diameter microspheres for
      modeling film dissolution into Lactated Ringer's solution. Experimental release
      profiles were modeled for each film from which the average release from alginate
      films (M AGCa  = 81%) was estimated to be twice the percentage associated with
      chitosan films (M CD  = 42%). The film comprised of 2.5% (w/v) medium MW
      chitosan/dextran 70 kDa (5:1) was selected for studying the release of 5
      Fluorouracil (5-FU) as a model hydrophobic drug. Diffusion coupled with film
      disintegration is immediate (t B  = 0) in case of encapsulated 5-FU as compared
      to the control film encapsulating microspheres characterized by t B  = 70 min +/-
      7 min. This shift in release profile and the ability to modulate the timing of
      membrane burst can be attributed to the approximate ratio (1: 505) in molecular
      size between drug and microsphere. This hypothesis has been validated by the film
      pore size measured to be 430 nm +/- 88 nm using atomic force microscopy.

PMID- 29470743
TI  - Progress and challenges in biomaterials used for bone tissue engineering:
      bioactive glasses and elastomeric composites.
AB  - Driven by the increasing economic burden associated with bone injury and disease,
      biomaterial development for bone repair represents the most active research area
      in the field of tissue engineering. This article provides an update on recent
      advances in the development of bioactive biomaterials for bone regeneration.
      Special attention is paid to the recent developments of sintered Na-containing
      bioactive glasses, borate-based bioactive glasses, those doped with trace
      elements (such as Cu, Zn, and Sr), and novel elastomeric composites. Although
      bioactive glasses are not new to bone tissue engineering, their tunable
      mechanical properties, biodegradation rates, and ability to support bone and
      vascular tissue regeneration, as well as osteoblast differentiation from stem and
      progenitor cells, are superior to other bioceramics. Recent progresses on the
      development of borate bioactive glasses and trace element-doped bioactive glasses
      expand the repertoire of bioactive glasses. Although boride and other trace
      elements have beneficial effects on bone remodeling and/or associated
      angiogenesis, the risk of toxicity at high levels must be highly regarded in the
      design of new composition of bioactive biomaterials so that the release of these
      elements must be satisfactorily lower than their biologically safe levels.
      Elastomeric composites are superior to the more commonly used thermoplastic
      matrix composites, owing to the well-defined elastic properties of elastomers
      which are ideal for the replacement of collagen, a key elastic protein within the
      bone tissue. Artificial bone matrix made from elastomeric composites can,
      therefore, offer both sound mechanical integrity and flexibility in the dynamic
      environment of injured bone.

PMID- 29470745
TI  - Estimated Brain Tissue Response Following Impacts Associated With and Without
      Diagnosed Concussion.
AB  - Kinematic measurements of head impacts are sensitive to sports concussion, but
      not highly specific. One potential reason is these measures reflect input
      conditions only and may have varying degrees of correlation to regional brain
      tissue deformation. In this study, previously reported head impact data recorded
      in the field from high school and collegiate football players were analyzed using
      two finite element head models (FEHM). Forty-five impacts associated with
      immediately diagnosed concussion were simulated along with 532 control impacts
      without identified concussion obtained from the same players. For each
      simulation, intracranial response measures (max principal strain, strain rate,
      von Mises stress, and pressure) were obtained for the whole brain and within four
      regions of interest (ROI; cerebrum, cerebellum, brain stem, corpus callosum). All
      response measures were sensitive to diagnosed concussion; however, large inter
      athlete variability was observed and sensitivity strength depended on measure,
      ROI, and FEHM. Interestingly, peak linear acceleration was more sensitive to
      diagnosed concussion than all intracranial response measures except pressure.
      These findings suggest FEHM may provide unique and potentially important
      information on brain injury mechanisms, but estimations of concussion risk based
      on individual intracranial response measures evaluated in this study did not
      improve upon those derived from input kinematics alone.

PMID- 29470746
TI  - Nitinol Stents in the Femoropopliteal Artery: A Mechanical Perspective on
      Material, Design, and Performance.
AB  - Endovascular stenting has matured into a commonly used treatment for peripheral
      arterial disease (PAD) due to its minimally invasive nature and associated
      reductions in short-term morbidity and mortality. The mechanical properties of
      the superelastic Nitinol alloy have played a major role in the explosion of
      peripheral artery stenting, with modern stents demonstrating reasonable
      resilience and durability. Yet in the superficial femoral and popliteal arteries,
      even the newest generation Nitinol stents continue to demonstrate clinical
      outcomes that leave significant room for improvement. Restenosis and progression
      of native arterial disease often lead to recurrence of symptoms and
      reinterventions that increase morbidity and health care expenditures. One of the
      main factors thought to be associated with stent failure in the femoropopliteal
      artery (FPA) is the unique and highly dynamic mechanical environment of the lower
      limb. Clinical and experimental data demonstrate that the FPA undergoes
      significant deformations with limb flexion. It is hypothesized that the inability
      of many existing stent designs to conform to these deformations likely plays a
      role in reconstruction failure, as repetitive movements of the leg and thigh
      combine with mechanical mismatch between the artery and the stent and result in
      mechanical damage to both the artery and the stent. In this review we will
      identify challenges and provide a mechanical perspective of FPA stenting, and
      then discuss current research directions with promise to provide a better
      understanding of Nitinol, specific features of stent design, and improved
      characterization of the biomechanical environment of the FPA to facilitate
      development of better stents for patients with PAD.

PMID- 29470747
TI  - Solid Stress Facilitates Fibroblasts Activation to Promote Pancreatic Cancer Cell
      Migration.
AB  - Pancreatic fibroblasts are continuously gaining ground as an important component
      of tumor microenvironment that dynamically interact with cancer cells to promote
      tumor progression. In addition, these tumor-infiltrated fibroblasts can acquire
      an activated phenotype and produce excessive amounts of extracellular matrix
      creating a highly dense stroma, a situation known as desmoplasia. Desmoplasia,
      along with the uncontrolled proliferation of cancer cells, leads to the
      development of compressive forces within the tumor, generating the so-called
      solid stress. Solid stress is previously shown to affect cancer cell
      proliferation and migration, however there is no pertinent study taking into
      account the effects of solid stress on fibroblasts and whether these effects
      contribute to tumor progression. In this work, we applied a defined compressive
      stress on pancreatic fibroblasts, similar in magnitude to that experienced by
      cells in native pancreatic tumors. Our results suggest that solid stress
      stimulates fibroblasts activation and strongly upregulates Growth Differentiation
      Factor-15 (GDF15) expression. Moreover, co-culture of compression-induced
      activated fibroblasts with pancreatic cancer cells significantly promotes cancer
      cell migration, which is inhibited by shRNA-mediated silencing of GDF15 in
      fibroblasts. Conclusively, our findings highlight the involvement of biophysical
      factors, such as solid stress, in tumor progression and malignancy revealing a
      novel role for GDF15.

PMID- 29470748
TI  - Investigating the Longitudinal Effect of Ovariectomy on Bone Properties Using a
      Novel Spatiotemporal Approach.
AB  - Osteoporosis is the most common bone disease. However, the mechanism of
      osteoporosis-induced alterations in bone is still unclear. The aim of this study
      was to investigate the effects of osteoporosis on the structural, densitometric
      and mechanical properties of the whole tibia using in vivo MUCT imaging,
      spatiotemporal analysis and finite element modeling. Twelve C57Bl/6 female mice
      were adopted. At 14 weeks of age, half of the mice were ovariectomized (OVX), and
      the other half were SHAM-operated. The whole right tibia was scanned using an in
      vivo MUCT imaging system at 14, 16, 17, 18, 19, 20, 21 and 22 weeks. The image
      datasets were registered in order to precisely quantify the bone properties. The
      results showed that OVX led to a significant increase in the endosteal area
      across the whole tibia 4 weeks after OVX intervention but did not have a
      significant influence on the periosteal area. Additionally, the bone volume and
      mineral content significantly decreased only in the proximal regions, but these
      decreases did not have a significant influence on the stiffness and failure load
      of the tibia. This study demonstrated the application of a novel spatiotemporal
      approach in the comprehensive analysis of bone adaptations in the spatiotemporal
      space.

PMID- 29470749
TI  - Editorial-ozone and plant life: the Italian state-of-the-art.

PMID- 29470750
TI  - Biological responses of aquatic organisms and assessment water contamination and
      ecotoxicity.

PMID- 29470752
TI  - Assessing changes in the toxicity of effluents from intensive marine fish farms
      over time by using a battery of bioassays.
AB  - Although intensive marine fish farming is often assumed to be eco-friendly, the
      associated activity can lead to chronic exposure of marine organisms to
      potentially toxic discharges. Moreover, despite the increasing popularity of
      integrated multi-trophic aquaculture (IMTA), studies of the effects of fish farm
      effluents are almost non-existent. In the present study, the changes in the toxic
      potential of effluents from five land-based marine fish farms in NW Spain
      subjected for different lengths of time to a biodegradation procedure (for 0, 48,
      120, and 240 h) were assessed in a battery of bioassays including organisms from
      different trophic levels (Vibrio fischeri, Isochrysis galbana, and Paracentrotus
      lividus). The results of the bioassays at the different times were then
      considered together with farm water flow in the Potential Ecotoxic Effects Probe
      (PEEP) index. Despite the high volumes of effluents discharged, the generally low
      toxicity of the effluents hinders assessment of potentially toxic effects.
      However, dose-response curves and statistical analysis demonstrated the existence
      of toxic effects during the first five days of the biodegradation procedure,
      especially immediately after sampling. The proposed modification of the PEEP
      index better reflects the changes in toxicity over time. Graphical abstract ?.

PMID- 29470751
TI  - Method development for determination of migrated phthalate acid esters from
      polyethylene terephthalate (PET) packaging into traditional Iranian drinking
      beverage (Doogh) samples: a novel approach of MSPE-GC/MS technique.
AB  - In the current study, a novel magnetic solid phase extraction (MSPE) technique
      combined with a gas chromatography/mass spectroscopy (GC/MS) was developed to
      determine the phthalate ester content of bottled Doogh samples. Doogh is a yogurt
      based drinking beverage, which is frequently consumed in Middle East and Balkans.
      It is produced by stirring yogurt in Chern separation machine and consists of
      substances such as water, yogurt, and salt in addition to aqueous extracts of
      native herbs. The magnetic multi-walled carbon nanotubes (MWCNT-Fe3O4) were used
      as adsorbents of phthalate acid esters (PAEs) due to a superior adsorption
      capability of hydrophobic compounds. In this context, the quantity of the
      extractable migrated phthalate esters (dibutyl phthalate (DBP), dimethyl
      phthalate (DMP), butyl benzyl phthalate (BBP), diethyl phthalate (DEP), di-N
      octyl phthalate (DNOP), and bis (2-ethylhexyl) phthalate (DEHP)) from
      polyethylene terephthalate (PET) bottles into Doogh samples was measured. The
      correlation between the concentration of migrated PAEs and some factors such as
      the type of Doogh (gaseous and without gas), difference in brand (five brands),
      volume (1500 and 300 mL), and the storage time also was investigated. The
      migration level into Doogh samples was increased by incorporating of gas as well
      as increasing the volume of PET bottles. Also, with elaborating of storage time,
      the migration of some phthalates such as DEHP (the mean from 2419.85 ng L-1 in
      the first week to 2716.15 ng L-1 in the second month), DEP, and total phthalate
      was increased. However, no significant difference in concentrations of migrated
      phthalate esters among different examined brands was noted. Finally, the
      concentration of migrated PAEs from bottle into all the examined Doogh samples
      was below the defined standards by EPA; 6 MUg/L for DEHP in drinking water.
      Graphical abstract ?.

PMID- 29470753
TI  - Spatial variation, source identification, and quality assessment of surface water
      geochemical composition in the Indus River Basin, Pakistan.
AB  - The Indus River Basin (IRB) with an area of 139,202 km2 is the lifeline river
      basin of Pakistan. An intensive study was conducted in six subcatchments of the
      IRB with five in the Upper Indus Basin (UIB) and one of the Lower Indus Basin
      (LIB; between Tarbela Dam and Panjand), i.e., the Gilgit River Basin (UIB-I),
      Hunza River Basin (UIB-II), UIB-III, UIB-IV and UIB-V, and LIB. A total of 84
      surface water samples were collected from main stream and tributaries from June
      to August, 2016. The pH, electric conductivity (EC), and total dissolved solids
      (TDS) were measured in situ, whereas major ions (Ca2+, Mg2+, K+, Na+, Cl-, SO42-,
      and NO3-) and Si were analyzed in the laboratory. The results exhibited alkaline
      pH (8.55 +/- 0.20) with diverse TDS (114.69 +/- 77.65 mg L-1) and ion
      concentrations that were characterized primarily by the Ca-Mg-HCO3 type in the
      whole basin. The average TDS in the UIB and LIB were 93.99 +/- 39.73 and 181.67
      +/- 167.82 mg L-1, respectively, under the influence of the arid to semi-arid
      climatic conditions and relatively higher anthropogenic interference in LIB
      compared to the UIB. The order of dominant major cations was different in the UIB
      and LIB, reflecting the diverse nature of geological formation. Gibbs plot,
      mixing diagrams, and ionic ratios were used to identify the controlling mechanism
      of river geochemistry in the IRB as carbonate weathering in general with
      different degrees of silicate weathering and minor contribution by evaporite
      dissolution. In addition, principal component/factor analysis also indicated that
      the major sources of dissolved loads in the basin are carbonates followed by
      silicates. Significant influences of silicate minerals were observed in the LIB,
      and there was a large contribution of evaporites in the UIB-II, UIB-III, and LIB.
      The suitability assessment showed that the river water fits the WHO permissible
      limits for drinking purposes from the perspective of major ions, whereas for
      irrigation purposes, most of the samples exhibited excellent and good levels
      except for a couple of permissible and doubtful levels from the Sawan and
      Deratang tributaries in the LIB, which may deteriorate the quality of soil and
      degrade the water quality downstream.

PMID- 29470755
TI  - Water planning in a mixed land use Mediterranean area: point-source abstraction
      and pollution scenarios by a numerical model of varying stream-aquifer regime.
AB  - Integrated hydrodynamic modelling is an efficient approach for making semi
      quantitative scenarios reliable enough for groundwater management, provided that
      the numerical simulations are from a validated model. The model set-up, however,
      involves many inputs due to the complexity of both the hydrological system and
      the land use. The case study of a Mediterranean alluvial unconfined aquifer in
      the lower Var valley (Southern France) is useful to test a method to estimate
      lacking data on water abstraction by small farms in urban context. With this
      estimation of the undocumented pumping volumes, and after calibration of the
      exchange parameters of the stream-aquifer system with the help of a river model,
      the groundwater flow model shows a high goodness of fit with the measured
      potentiometric levels. The consistency between simulated results and real
      behaviour of the system, with regard to the observed effects of lowering weirs
      and previously published hydrochemistry data, confirms reliability of the
      groundwater flow model. On the other hand, accuracy of the transport model output
      may be influenced by many parameters, many of which are not derived from field
      measurements. In this case study, for which river-aquifer feeding is the main
      control, the partition coefficient between direct recharge and runoff does not
      show a significant effect on the transport model output, and therefore,
      uncertainty of the hydrological terms such as evapotranspiration and runoff is
      not a first-rank issue to the pollution propagation. The simulation of pollution
      scenarios with the model returns expected pessimistic outputs, with regard to
      hazard management. The model is now ready to be used in a decision support system
      by the local water supply managers.

PMID- 29470754
TI  - Mitigation measures to avert the impacts of plastics and microplastics in the
      marine environment (a review).
AB  - The increasing demand for and reliance on plastics as an everyday item, and rapid
      rise in their production and subsequent indiscriminate disposal, rise in human
      population and industrial growth, have made the material an important
      environmental concern and focus of interest of many research. Historically,
      plastic production has increased tremendously to over 250 million tonnes by 2009
      with an annual increased rate of 9%. In 2015, the global consumption of plastic
      materials was reported to be > 300 million tonnes and is expected to surge
      exponentially. Because plastic polymers are ubiquitous, highly resistant to
      degradation, the influx of these persistent, complex materials is a risk to human
      and environmental health. Because microplastics are principally generated from
      the weathering or breakdown of larger plastics (macroplastics), it is noteworthy
      and expedient to discuss in detail, expatiate, and tackle this main source. Macro
      and microplastic pollution has been reported on a global scale from the poles to
      the equator. The major problem of concern is that they strangulate and are
      ingested by a number of aquatic biota especially the filter feeders, such as
      molluscs, mussels, oysters, from where it enters the food chain and consequently
      could lead to physical and toxicological effects on aquatic organisms and human
      being as final consumers. To this end, in order to minimise the negative impacts
      posed by plastic pollution (macro- and microplastics), a plethora of strategies
      have been developed at various levels to reduce and manage the plastic wastes.
      The objective of this paper is to review some published literature on management
      measures of plastic wastes to curb occurrence and incidents of large- and
      microplastics pollution in the marine environments.

PMID- 29470756
TI  - Study on transport and transformation of contaminant through layered soil with
      large deformation.
AB  - Based on large-deformation consolidation theory and the advection-dispersion
      equation of contaminant in saturated porous media, a one-dimensional theoretical
      model for coupled large-deformation and solute transport through layered finite
      soil is presented. This model comprehensively takes the effect of soil weight,
      sorption, and biodegradation into account. Model validation and applications are
      achieved through case studies of double-layered finite soil, with the transport
      and transformation process of contaminant being reproduced numerically. It is
      found that the breakthrough time of contaminant obtained from the linear
      adsorption solution is greater than the case of the non-linear adsorption
      solution, which can provide a reference for the design of landfill liner.
      Simulation results also indicate that relevant factors affect the transport of
      contaminant in layered soil interdependently; comprehensive study is required to
      assess the capacity of natural clay barrier for contaminant transportation.

PMID- 29470757
TI  - The Pediatric Committee of the American Autonomic Society.

PMID- 29470758
TI  - Cyclic vomiting syndrome: the nervous system has the guts.

PMID- 29470760
TI  - Organized Activity Involvement among Urban Youth: Understanding Family- and
      Neighborhood- Level Characteristics as Predictors of Involvement.
AB  - Research examining factors that predict youth's involvement in organized
      activities is very limited, despite associations with positive outcomes. Using
      data from 1043 youth (49% female; 46.4% Hispanic, 35.4% African American, 14.0%
      Caucasian, and 4.2% other) from the Project on Human Development in Chicago
      Neighborhoods, this study examined how characteristics of parents (supervision,
      warmth) and neighborhoods (perceived neighborhood safety and collective efficacy)
      predict patterns of adolescents' involvement in organized activities concurrently
      (i.e., intensity) and longitudinally (i.e., type and breadth). Parental
      supervision predicted adolescents' participation in organized activities across
      multiple waves. Neighborhood violence was positively associated with concurrent
      participation in organized activities after controlling for socioeconomic status
      (SES), whereas higher neighborhood collective efficacy predicted greater breadth
      in organized activity participation across time. These findings have important
      implications regarding how to attract and sustain organized activity
      participation for low-income, urban youth.

PMID- 29470759
TI  - Problem Gambling and Delinquent Behaviours Among Adolescents: A Scoping Review.
AB  - Despite many studies indicating an association between problem gambling and
      delinquent behaviours among adolescents, there has been no effort to
      systematically analyze the state of the literature on this relationship. To fill
      this gap, we conducted a scoping review of the literature published between 2000
      and 2016 on problem gambling and delinquent behaviours among adolescents. We
      searched twelve databases and reviewed reference lists to identify eligible
      studies. Search terms included a combination of medical subject headings and
      keywords for gambling, youth, and delinquency, which were combined with the
      Boolean operator "AND". 1795 studies were identified through the literature
      search. Nine studies were eligible for inclusion. All of the studies were
      conducted in North America, with primarily male participants, and most of the
      data were cross-sectional. No qualitative studies met the inclusion criteria.
      Screening tools used to measure problem gambling were inconsistent, making
      comparisons across studies difficult. We found a consistent moderate to strong
      association between problem gambling and delinquent behaviour. Only one study
      presented associations by socio-economic status and none considered gender, sex
      or ethnic differences. Studies in the review showed that problem gambling is
      associated with both violent and non-violent behaviours among adolescents. These
      associations may suggest that problem gambling and delinquent behaviours have
      common risk factors and reflect a syndrome of risky behaviours best targeted
      through prevention and treatment that is holistic and considers the context in
      which the youth is situated. Further research is warranted to better understand
      the relationship between problem gambling and delinquent behaviours.

PMID- 29470761
TI  - The Rise and Fall of Depressive Symptoms and Academic Stress in Two Samples of
      University Students.
AB  - Self-reported depressive experiences are common among university students.
      However, most studies assessing depression in university students are cross
      sectional, limiting our understanding of when in the academic year risk for
      depression is greatest and when interventions may be most needed. We examined
      within-person change in depressive symptoms from September to April. Study 1 (N =
      198; 57% female; 72% white; Mage = 18.4): Depressive symptoms rose from
      September, peaked in December, and fell across the second semester. The rise in
      depressive symptoms was associated with higher perceived stress in December.
      Study 2 (N = 267; 78.7% female; 67.87% white; Mage = 21.25): Depressive symptoms
      peaked in December and covaried within persons with perceived stress and academic
      demands. The results have implications for understanding when and for whom there
      is increased risk for depressive experiences among university students.

PMID- 29470762
TI  - Intergenerational Transmission of Educational Aspirations in Chinese Families:
      Identifying Mediators and Moderators.
AB  - Parents' educational aspirations for youth play an important role in shaping
      youth's own educational aspirations; however, little is known about how and in
      what context parents may transmit their aspirations to youth effectively. This is
      of particular interest and import to be examined in Chinese families, given
      Chinese cultural emphasis on educational achievement and Chinese youth's
      outstanding academic performance internationally. By integrating several key
      theories of motivation and parental socialization (i.e., the expectancy-value
      model of academic achievement, the two-step model of value transmission, the
      contextual model of parenting, and the self-determination theory), the current
      study investigated simultaneously the mediating roles of parental involvement in
      youth's learning and youth's perceptions of parental aspirations, as well as the
      moderating role of parental warmth in the intergenerational transmission process
      of educational aspirations in Chinese families. A two-wave longitudinal study
      spanning about half a year was conducted among 323 Chinese seventh graders (54%
      female; Mage = 13.25 years) and one of their parents (median educational
      attainment = completion of high school, median monthly income = USD 766-1226). It
      was found that parental educational aspirations for youth were related positively
      both indirectly through parental involvement and directly to youth's perceptions
      of parental aspirations, which in turn were associated positively with youth's
      own educational aspirations about half a year later. It was also found that
      parental educational aspirations for youth and youth's own educational
      aspirations were associated positively with each other only when youth reported
      experiencing high levels of parental warmth, but unrelated when youth reported
      experiencing low levels of parental warmth, whereas such moderating effects of
      parental warmth were absent on the links from parental aspirations to youth's
      perceptions of parental aspirations and parental involvement. These findings
      highlight the importance of integrating multiple theories to understand parent-to
      youth transmission of educational aspirations in non-western cultures, which
      helps not only reveal generalizability, as well as boundary conditions for
      Western-originated theories, but also inform practical endeavors at promoting
      youth's educational achievement worldwide to draw on strengths of different
      cultures.

PMID- 29470763
TI  - A Rapid On-Site Assay for the Detection of Influenza A by Capillary Convective
      PCR.
AB  - BACKGROUND: Morbidity and mortality from influenza A (Flu A) have increased in
      recent years. Timely diagnosis and management are critical for disease control.
      Therefore, the development of a rapid, accurate, and portable analytical method
      for on-site analysis is imperative. OBJECTIVES: The aim of this work was to
      develop a rapid, on-site, automated assay for the detection of Flu A and to
      evaluate the assay. METHODS: A handheld instrument (TD-01) based on capillary
      convective polymerase chain reaction (PCR) was developed for rapid on-site
      detection of Flu A. Since a previous version of the instrument, an automated
      motion mechanism has been introduced to TD-01 to achieve RNA automated testing.
      The primers and probe used for Flu A detection were designed according to the Flu
      A gene sequence of matrix proteins. Finally, we evaluated the detection spectra,
      sensitivity, specificity, and diagnostic performance of the assay. RESULTS: The
      TD-01 was able to successfully automatically detect Flu A RNA within 30 min.
      Results for serially diluted viruses indicated that the lower limit of detection
      for Flu A was 0.1 TCID50/ml (50% tissue culture infective dose). After evaluating
      known virus stocks, including 15 strains of Flu A, four strains of Flu B, and two
      strains of respiratory syncytial virus (RSV), the assay had a favorable detection
      spectrum and no obvious cross-reactivity. Method verification based on 554
      clinical samples indicated that the sensitivity and specificity of TD-01 were
      98.30% (231/235) and 98.75% (315/319), respectively. CONCLUSIONS: The results
      indicate that Flu A detection by TD-01 is particularly suitable for on-site
      testing and has the potential for application in point-of-care testing.

PMID- 29470764
TI  - Levels of Circulating mRNA for the Tenascin-X (TNXB) Gene in Maternal Plasma at
      the Second Trimester in Pregnancies with Isolated Congenital Ventricular Septal
      Defects.
AB  - OBJECTIVE: Maternal plasma is a source of circulating placental nucleic acids. In
      this study, we validated previous observations on abnormal levels of circulating
      messenger RNA (mRNA) for the tenascin-X gene in pregnancies with ventricular
      septal defects in the second trimester of pregnancy. METHODS: This was a
      bicentric retrospective study conducted from March 2016 to July 2017. Real-time
      polymerase chain reaction was used to identify abnormally expressed genes,
      comparing ten women carrying a euploid fetus with ventricular septal defects to
      30 controls at 19-24 weeks of gestation. The univariable analysis was used to
      determine whether the mean mRNA for the tenascin-X gene values would differ from
      the expected values for the controls. RESULTS: mRNA for tenascin-X gene values
      was higher in ventricular septal defects, 4.38 +/- 3.01 versus 1.00 +/- 0.80. The
      result was still significant even after adjustment for gestational age.
      CONCLUSIONS: These data confirm previous studies on the specific association of
      mRNA species and type of congenital heart defect and confirm that ventricular
      septal defects are associated with abnormal mRNA for the tenascin-X gene. The
      positive predictive value of this molecular marker in the general population
      should be assessed through prospective studies.

PMID- 29470765
TI  - Angiotensin II receptor blockers for the treatment of portal hypertension in
      patients with liver cirrhosis: a systematic review and meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Randomized controlled trials (RCTs) showed inconsistent results
      regarding the efficacy of angiotensin II receptor blockers (ARBs) on portal
      pressure as indicated by hepatic venous pressure gradient (HVPG). METHODS: A meta
      analysis of RCTs was performed to evaluate the influence of ARBs treatment on
      HVPG. PubMed, Embase, and Cochrane's Library were searched for relevant RCTs. A
      fixed or a randomized effect model was used to pool the results according the
      heterogeneity. Subgroup analyses were performed to explore the source of
      heterogeneity. RESULTS: Eleven RCTs with 394 patients were included. ARBs
      treatment did not significantly change HVPG as compared with controls (weighted
      mean difference [WMD] = -0.63, 95% confidence interval [CI] -1.73 to 0.47 mmHg, p
      = 0.26; I2 = 60%). These results were consistent in studies comparing ARBs with
      propranolol (WMD = -0.40, 95% CI -2.22 to 1.41 mmHg, p = 0.67; I2 = 68%), and
      those comparing ARBs with non-active controls including placebo or no treatment
      (WMD = -1.05, 95% CI -2.33 to 0.24 mmHg, p = 0.13; I2 = 44%). These results were
      also not affected by the individual ARBs used. Moreover, treatment of ARBs
      significantly reduced mean arterial blood pressure (WMD = -6.12, 95% CI -9.69 to 
      2.55 mmHg, p = 0.008; I2 = 53%), and the risk of symptomatic hypotension was
      increased (RR = 4.13, 95% CI 0.94 to 18.18, p = 0.06; I2 = 0%). CONCLUSIONS: ARBs
      did not reduce portal pressure in patients with cirrhosis; moreover, the risk of
      symptomatic hypotension may increase.

PMID- 29470766
TI  - Haloperidol attenuates Methylphenidate and Modafinil induced behavioural
      sensitization and cognitive enhancement.
AB  - Previous studies have demonstrated that repeated psychostimulant administration
      produces behavioural sensitization and cognitive tolerance. Brain dopaminergic
      system and the involvement of dopamine D2-receptors are considered to be
      important in psychostimulant-induced sensitization. Study designed to compared
      the motor activity by using familiar and novel enviroments and cognitive effects
      by water maze and passive avoidance test after long term administration of
      methylphenidate(at the dose 0.6 mg/kg/day, 2.5 mg/kg/day and 10 mg/kg/day) and
      modafinil (50 mg/kg/day, 64 mg/kg/day and 75 mg/kg/day) in rats. The effects of
      challenge dose of haloperidol (at the dose of 1 mg/kg i.p.) has monitored to
      visualize any subsensitization or supersensitization of D2 receptors. We found
      that motor activity and cognitive performance was increased in all doses and
      sensitization effect was more pronounced after 13 days of drug administration
      were greater at high than low and medium doses.Challenge dose of haloperidol
      attenuate motor activity in familiar and novel environment and impaired cognition
      in water maze and passive avoidance test in all treated rats. The effect of
      Haloperidol in high dose treated rats were however somewhat greater than low and
      medium dose treated rats following methylphenidate and modafinil administration.
      Increased response of haloperidol in methylphenidate treated rats can be
      explained in term of supersensitization of D2 receptors which is greater in high
      dose treated rats. The results show that the role of D2 receptors to develop side
      effects such as behavioural sensitization and cognitive tolerance by the long
      term administration of psychostimulants is of sufficient importance and helpful
      in understanding the mechanisms underlying the undesirable effects of
      psychostimulants.

PMID- 29470767
TI  - The effects of tramadol administration on hippocampal cell apoptosis, learning
      and memory in adult rats and neuroprotective effects of crocin.
AB  - Tramadol, a frequently used pain reliever drug, present neurotoxic effects
      associated to cognitive dysfunction. Moreover, crocin has been reported to have
      neuroprotective effects. The aim of this study was to assess crocin's capacity to
      protect learning, and memory abilities on tramadol-treated rats. A total of 35
      rats were divided into five groups: Control, Saline, tramadol (50 mg/kg),
      tramadol + crocin(30 mg/kg), crocin groups and treated orally for 28 consecutive
      days. Morris water maze (MWM) and passive avoidance (PA) tests were done,
      followed by dissection of the rat's brains for toluidine blue and TUNEL staining.
      In MWM test, tramadol group spent lower time and traveled shorter distance in the
      target quadrant (Q1) (P < 0.05). On the other side, the traveled distance in
      tramadol-crocin group was higher than tramadol (P < 0.05). In PA test, both the
      delay for entering the dark, and the total time spent in the light compartment
      decreased in tramadol comparing to the control group (P < 0.05), while it
      increased in tramadol-crocin compared with the tramadol group (P < 0.05). In
      tramadol-treated animals, the dark neurons (DNs) and apoptotic cells in CA1, CA3
      and DG increased (P < 0.05), while concurrent intake of crocin decreased the
      number of DNs and apoptotic cells in these areas (P < 0.05). Crocin was able to
      improve learning and memory of tramadol-treated rats and also decreased DNs and
      apoptotic cells in the hippocampus. Considering these results, the potential
      capacity of crocin for decreasing side effects of tramadol on the nervous system
      is suggested.

PMID- 29470768
TI  - Invivo biocompatibility determination of acellular aortic matrix of buffalo
      origin.
AB  - In the present study, biocompatibility of native, acellular, 1,4-butanediol
      diglycidylether and 1-ethyl-3-(3-dimethyl aminopropyl carbodiimide (EDC) cross
      linked acellular aortic grafts was evaluated following subcutaneous implantation
      in guinea pigs. Biocompatibility was evaluated based on macroscopic,
      histopathological observations and immune responses elicited by the implanted
      grafts. Results showed that macroscopically, no abnormal cellular reaction was
      observed at the host-graft junction in any of the implanted animals.
      Histopathological observations revealed that the inflammatory response was mild
      during first 15 days post-implantation and increased at 30 days post-implantation
      in acellular and cross-linked tissues. By day 60, marked ingrowth of host tissue
      was observed in EDC cross-linked acellular aortic grafts. ELISA and lymphocyte
      proliferation assay revealed that animals implanted with EDC grafts showed least
      immune response when compared to others. Therefore, it was concluded that EDC
      cross-linked acellular aortic grafts were more compatible and had better handling
      qualities than the other cross-linked grafts.

PMID- 29470769
TI  - Advancement of wound care from grafts to bioengineered smart skin substitutes.
AB  - This review gives a brief description on the skin and its essential functions,
      damages or injury which are common to the skin and the role of skin substitute to
      replace the functions of the skin soon after an injury. Skin substitutes have
      crucial role in the management of deep dermal and full thickness wounds. At
      present, there is no skin substitute in the market that can replace all the
      functions of skin 'and the research is still continuing for a better alternative.
      This review is an attempt to recollect and report the past efforts including skin
      grafting and recent trends like use of bioengineered smart skin substitutes in
      wound care. Incorporation functional moieties like antimicrobials and wound
      healing agents are also described.

PMID- 29470770
TI  - Antibacterial effects of silver-zirconia composite coatings using pulsed laser
      deposition onto 316L SS for bio implants.
AB  - Bacterial invasion on biomedical implants is a challenging task for long-term and
      permanent implant fixations. Prevention of initial bacterial adherence on
      metallic implants is an important concern to avoid extracellular matrix (biofilm)
      secretion from bacteria that is resistant to antibacterial agents. In order to
      overcome this defect, recently, surface coatings such as zirconia (ZrO2) with
      higher smoothness have been shown to improve implants durability. In the present
      study, pulsed laser deposition (PLD) was used to deposit ZrO2 and silver (Ag)
      ZrO2 composite coatings onto 316L stainless steel (316L SS). Phase purity,
      surface roughness and surface morphology, thickness of the coatings and elemental
      compositions of the coatings were analyzed using X-ray diffraction (XRD), atomic
      force microscopy (AFM) and scanning electron microscopy (SEM) with energy
      dispersive X-ray spectroscopy (EDS). Total viable count (TVC) and epifluorescence
      microscopy analysis were studied to evaluate antimicrobial efficiency of ZrO2 and
      Ag-ZrO2 composite coatings using gram negative (gram -ve) Escherichia coli
      (E.coli) and gram positive (gram +ve) Staphylococcus aureus (S.aureus). On the
      basis of the present study, it could be speculated that ZrO2 coatings exhibited
      antibacterial activity against only E.coli, whereas Ag-ZrO2 composite coatings
      showed superior activity against E.coli and S.aureus strains.

PMID- 29470771
TI  - In vitro-in vivo correlation from lactide-co-glycolide polymeric dosage forms.
AB  - The objective of this study was to compare the in vitro behavior of four long
      acting subcutaneous risperidone formulations with in vivo performance, with the
      intent of establishing an IVIVC. Two copolymers of PLGA (50:50 and 75:25) were
      used to prepare four microsphere formulations of risperidone, an atypical
      antipsychotic. In vitro behavior was assessed at the physiological temperature
      (37  degrees C) using the 'modified dialysis' technique. The in vitro release
      profile demonstrated rank order behavior with Formulations A and B, prepared
      using the 50:50 copolymer, exhibiting rapid drug release, while Formulations C
      and D, prepared using 75:25 PLGA, released drug in a slower manner. In vivo
      profiles were obtained by two approaches, i.e., deconvolution using the Nelson
      Wagner equation (the FDA recommended approach) and using fractional AUC. With
      both in vivo approaches, the 50:50 PLGA preparations released drug faster than
      the 75:25 PLGA microspheres, exhibiting the same rank order observed in vitro.
      Additionally, profiles for the four formulations obtained using the deconvolution
      approach were nearly superimposable with fractional AUC, implying that the latter
      procedure could be used as a substitute for the Nelson-Wagner method. A
      comparison of drug release profiles for the four formulations revealed that in
      three of the four formulations, in vivo release was slightly faster than that in
      vitro, but the results were not statistically significant (P > 0.0001). An
      excellent linear correlation (R2 values between 0.97 and 0.99) was obtained when
      % in vitro release for each formulation was compared with its corresponding in
      vivo release profile, obtained by using fraction absorbed (Nelson-Wagner method)
      or fractional AUC. In summary, using the four formulations that exhibited
      different release rates, a Level A IVIVC was established using the FDA
      recommended deconvolution method and fractional AUC approach. The excellent
      relationship between in vitro drug release and the amount of drug absorbed in
      vivo in this study was corroborated by the nearly 1:1 correlation (R2 greater
      than 0.97) between in vitro release and in vivo performance. Thus, the results of
      the current study suggest that proper selection of an in vitro method to assess
      drug release from long-acting injectables will aid in obtaining a Level A IVIVC.

PMID- 29470772
TI  - Robotics confers an advantage in right hemicolectomy with intracorporeal
      anastomosis when matched against conventional laparoscopy.
AB  - Comparisons between robotic and laparoscopic right hemicolectomy have been
      confounded by variations in operative technique. This study evaluates the two
      procedures after standardizing the intraoperative steps and perioperative
      management. Patients who underwent robotic right hemicolectomy with
      intracorporeal bowel anastomosis between July 2015 and June 2017 were matched
      with a laparoscopic group. Perioperative management was in accordance to an
      enhanced recovery protocol. Outcomes and histopathological data were compared.
      Thirty-two patients were included. Amongst the patients who did not undergo
      complete mesocolic excision, the median operative time did not differ between the
      two groups (p = 0.413). The robotic group recorded a statistically shorter time
      for intracorporeal anastomosis (13 vs 19 min, p = 0.024). Postoperative recovery
      and complication rates were similar, except for a greater lymph node harvest in
      the robotic group (41 vs 31, p = 0.038). Robotic surgery achieves short-term
      results comparable to existing conventional laparoscopy, notwithstanding the
      advantages of enhanced ergonomics.

PMID- 29470773
TI  - Estimation of linear energy transfer distribution for broad-beam carbon-ion
      radiotherapy at the National Institute of Radiological Sciences, Japan.
AB  - A treatment of carbon-ion radiotherapy (CIRT) is generally evaluated using the
      dose weighted by relative biological effectiveness (RBE) while ignoring the
      radiation quality varying in the patient. In this study, we have developed a
      method of estimating linear energy transfer (LET) from the RBE in an archived
      treatment plan to represent the radiation quality of the treatment. The LET in a
      beam database was associated with the RBE by two fitting functions per energy,
      one for the spread-out Bragg peak (SOBP) and the other for shallower depths, to
      be differentiated by RBE per energy per modulation. The estimated LET was
      generally consistent with the original calculation within a few keV/MUm, except
      for the overkill region near the distal end of SOBP. The knowledge of
      experimental radiobiology can thereby be associated with CIRT treatments through
      LET, which will potentially contribute to deeper understanding of clinical
      radiobiology and further optimization of CIRT.

PMID- 29470774
TI  - Multi-indication and Combination Pricing and Reimbursement of Pharmaceuticals:
      Opportunities for Improved Health Care through Faster Uptake of New Innovations.
AB  - Many pharmaceuticals are effective in multiple indications and the degree of
      effectiveness may differ. A product-based pricing and reimbursement system with a
      single price per product is insufficient to reflect the variable values between
      different indications. The objective of this article is to present examples of
      actual pricing and reimbursement decisions using current value-based pricing in
      Sweden and to discuss their implications and possible solutions. The value of
      several cancer drugs was estimated for various indications based on a willingness
      to-pay threshold of 1 million SEK (EUR 104,000) per QALY gained. For some drugs,
      the estimated value was higher than the drug acquisition cost in several
      indications, whilst in others, the estimated value was lower than the drug
      acquisition cost. Drugs used in combination present a special case. If a drug
      prolongs survival and consequently also a continued use of the anchor drug, the
      combination use may not be cost effective even at a zero price. In a product
      based pricing and reimbursement system, patients may not get access to drugs or
      access may be delayed and manufacturers may be discouraged to invest in future
      indications. To overcome these issues, there are several approaches to link price
      and value. One approach is a "weighted-average" price based on an average of the
      value across all indications. Another is "multi-indication pricing," which
      enables price differentiation between indications. However, there are several
      barriers for applying multi-indication pricing and reimbursement schemes. One
      barrier is the lack of existing administrative infrastructure to track patients'
      indications.

PMID- 29470775
TI  - Influence of body mass index in anti-Mullerian hormone levels in 951 non
      polycystic ovarian syndrome women followed at a reproductive medicine unit.
AB  - PURPOSE: Anti-Mullerian hormone (AMH) is a useful marker of ovarian reserve.
      Obesity/overweight are increasing and may affect the reproductive health.
      Previous studies regarding the effect of body mass index (BMI) on AMH levels are
      discordant. Our main goal was to evaluate the influence of BMI on AMH levels in
      women without polycystic ovarian syndrome. METHODS: Revision of medical records
      of 951 women who performed AMH determinations as part of their fertility workup,
      between 2011 and 2016. RESULTS: Median AMH concentration was 1.75 [interquartile
      range (IQR) 2] ng/mL (12.9 pmol/mL) and median age at AMH determination was 35
      (IQR 6) years. These women evidenced a median BMI of 23 (IQR 5) kg/m2. Caucasian
      women were more represented [889(89.3%)]. Smoking habits (present/past) were
      present in 359(36.1%), and 147(14.8%) harboured a history of ovarian surgery. On
      univariable analysis AMH was not correlated with BMI (r = 0.048/p = 0.135); the
      only factors influencing AMH were age (p < 0.001), ethnicity (p = 0.004), and
      previous ovarian surgery (p < 0.001). On multivariable analysis, age was the only
      variable significantly associated with AMH, evidencing a reduction of 6.2% for
      each additional year (p < 0.0001). Furthermore, we verified a trend suggesting an
      AMH reduction of 22% (p = 0.08) in black patients comparing with the caucasian
      ones, when controlling for the other variables. CONCLUSION: We report one of the
      largest series evaluating the influence of BMI on AMH levels and, consequently,
      on ovarian reserve. BMI does not seem to affect AMH levels. The reported concerns
      on infertility in overweight and obese women may be related to follicular
      development/oocyte maturation or endometrial disorders, rather than decreased
      ovarian reserve.

PMID- 29470776
TI  - A path model analysis on predictors of dropout (at 6 and 12 months) during the
      weight loss interventions in endocrinology outpatient division.
AB  - INTRODUCTION: This study aimed to identify the dropout rate at 6 and 12 months
      from the first outpatient visit, and to analyze dropout risk factors among the
      following areas: biochemical examinations, anthropometric measures, psychological
      tests, personal data, and life attitude such as smoking, physical activity, and
      pathologies. METHODS: This is a retrospective longitudinal observational study.
      Patients undergo an outpatient endocrinology visit, which includes collecting
      biographical data, anthropometric measurements, physical and pathological
      history, psychological tests, and biochemical examinations. RESULTS: The sample
      consists of 913 subjects (682 women and 231 men), with an average age of 50.88
      years (+/-15.80) for the total sample, with a BMI of 33.11 +/- 5.65 kg/m2. 51.9%
      of the patients abandoned therapy at 6 months after their first visit, and
      analyzing the dropout rate at 12 months, it appears that 69.5% of subjects
      abandon therapy. The main predictor of dropout risk factors at 6 and 12 months is
      the weight loss during the first 3 months (p < 0.05). As regards the
      hematological predictors, white blood cell and iron level stated dropout at 12
      months. Patients who introduced physical activity had a reduction of - 17% (at 6
      months) and -13% (at 12 months) of dropout risk (p < 0.05). As regards the
      "worker" status, patients classified as"retired" had a decrease risk of dropout
      vs. other categories of worker (i = 0.58; p < 0.05). Dropout risk at 12 months
      decrease in patients with a previous history of cancer, Endocrine and psychic and
      behavioral disorders (p < 0.001). CONCLUSIONS: The main factor that predisposes
      patients to continue therapy or to abandon it is the success (or failure) of the
      diet in the initial period, based on weight lost (or not lost) in the early
      months of the initiation of therapy. Furthermore, considerable differences were
      found in different categories of "workers", and with previous "pathologies". The
      level of physical activity and previous diseases also seem to be predictors of
      dropout.

PMID- 29470778
TI  - Guselkumab for the Treatment of Psoriasis.
AB  - Psoriasis is a common, chronic, immune-mediated, inflammatory skin disease with
      systemic involvement and significant impact on patients' quality of life. Several
      biologic treatments have been developed in recent decades, such as tumor necrosis
      factor (TNF)-alpha inhibitors, a non-selective interleukin (IL)-23 inhibitor
      (ustekinumab, which also inhibits IL-12), and-most recently-IL-17 inhibitors.
      Guselkumab is a novel biological therapy that selectively targets IL-23 and is
      the first-in-class selective IL-23 inhibitor approved to treat moderate-to-severe
      plaque psoriasis. These inhibitors are expected to have some advantages over the
      highly effective IL-17 inhibitors, as they do not worsen inflammatory bowel
      disease and are not involved in the development of candida infections.
      Additionally, selective inhibition of IL-23 may have additional benefits over
      ustekinumab as the IL-12-dependent cascades remain functional. These benefits
      include a decrease in IL-17A-producing T cells in the skin and the promotion of
      an anti-inflammatory effect through production of interferon-gamma and IL-10. In
      terms of efficacy, guselkumab showed promising results in the treatment of
      psoriasis and psoriatic arthritis, although it did not show significant clinical
      improvement in rheumatoid arthritis. Studies in other inflammatory diseases and
      Crohn's disease are expected to begin soon. Overall, guselkumab was well
      tolerated; the most common adverse event was nasopharyngitis. Head-to-head
      studies comparing IL-23 inhibitors with agents in different classes, namely IL-17
      inhibitors, will be crucial to establish the true role of these agents in
      psoriasis treatment.

PMID- 29470777
TI  - Pleiotropic effects of heparins: does anticoagulant treatment increase survival
      in cancer patients?
AB  - The association between venous thromboembolism (VTE) and cancer has been
      recognized for more than 100 years. Numerous studies have been performed to
      investigate strategies to decrease VTE incidence and to establish whether
      treating VTE impacts cancer progression and overall survival. Accordingly, it is
      important to understand the role of the hemostatic system in tumorigenesis and
      progression, as there is abundant evidence associating it with cell survival and
      proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis
      formation. In attempts to further the scientific evidence, several studies
      examine survival benefits in cancer patients treated with anticoagulant therapy,
      specifically treatment with vitamin K antagonists, unfractionated heparin, and
      low-molecular-weight heparin. Several studies and meta-analyses have been
      conducted with a special focus on brain tumors. However, no definitive
      conclusions have been obtained, and more well-designed clinical trials are
      needed.

PMID- 29470779
TI  - Current progress on bio-based polymers and their future trends.
AB  - This article reviews the recent trends, developments, and future applications of
      bio-based polymers produced from renewable resources. Bio-based polymers are
      attracting increased attention due to environmental concerns and the realization
      that global petroleum resources are finite. Bio-based polymers not only replace
      existing polymers in a number of applications but also provide new combinations
      of properties for new applications. A range of bio-based polymers are presented
      in this review, focusing on general methods of production, properties, and
      commercial applications. The review examines the technological and future
      challenges discussed in bringing these materials to a wide range of applications,
      together with potential solutions, as well as discusses the major industry
      players who are bringing these materials to the market.

PMID- 29470780
TI  - Ecological preferences and seasonal dynamics of ticks (Acari: Ixodidae) on and
      off bovine hosts in the Eastern Cape Province, South Africa.
AB  - A total of 31,425 ticks were collected from 10 cattle and also from six drag
      samples during the 12-month study period. Adult ticks were removed from the right
      hand side of each animal and all instars of ticks were placed in containers
      filled with 70% ethanol. Based on morphological traits, 10 tick species were
      identified: Rhipicephalus (Boophilus) decoloratus (32.5%), R. evertsi evertsi
      (18.8%), R. appendiculatus (17.3%), Amblyomma hebraeum (16.3%), R. simus (7.7%),
      Ixodes pilosus (3.8%), Hyalomma rufipes (3.5%), R. follis (0.08%), Haemaphysalis
      elliptica (0.04%), H. silacea (0.02%). The southern African yellow dog tick, H.
      elliptica, was only found on vegetation. The agro-ecological zones differ
      significantly in tick species and their distribution. The A. hebraeum and R.
      evertsi evertsi counts were higher in Kowie Thicket (KT) during summer season
      (2.05 +/- 0.01 and 1.00 +/- 0.09, respectively) compared to Bedford Dry Grassland
      (BDG) and Bhisho Thornveld (BT) veld types. In all vegetation types, R.
      appendiculatus had higher counts in KT in spring (0.91 +/- 0.08), summer (0.78 +/
      0.08) and winter (0.78 +/- 0.08). Rhipicephalus (Boophilus) decoloratus was more
      frequent in the BT (1.78 +/- 0.11) during the summer season. BDG had lower tick
      infestation with R. evertsi evertsi being the most frequent species in summer. No
      H. rufipes was collected in the KT. Of epidemiological interest, R. (B.)
      microplus was absent in the study area which needs further investigation. Within
      the context of this study, we found agro-ecological differences and seasonal
      variations to have influence on tick species distribution.

PMID- 29470781
TI  - Gender-specific differences in cannibalism between a laboratory strain and a
      field strain of a predatory mite.
AB  - Many phytoseiid species, including Phytoseiulus persimilis, are known to engage
      in cannibalism when food is scarce and when there is no possibility to disperse.
      In nature adult females of P. persimilis are known to disperse when prey is
      locally depleted. Males, in contrast, are expected to stay and wait for potential
      mates to mature. During this phase, males can obtain food by cannibalizing.
      Therefore, we hypothesize that male P. persimilis exhibit a higher tendency to
      cannibalize than females. Because rearing conditions in the laboratory usually
      prevent dispersal, prolonged culturing may also affect cannibalistic behavior. We
      hypothesize that this should especially affect cannibalism by females, because
      they consume far more food. We tested these hypotheses by comparing males and
      females from two strains, one of which had been in culture for over 20 years,
      whereas the other was recently collected from the field. It is known that this
      predator can discriminate between kin and non-kin and prefers cannibalizing the
      latter, hence to construct lines with high relatedness we created isofemale lines
      of these two original strains. We subsequently tested to what extent the adult
      females and males of the original strains and the isofemale lines cannibalized
      conspecific larvae from the same strain/line in a closed system. Relatedness with
      the victims did not affect cannibalistic behavior, but males engaged more often
      in cannibalism than females, and females of the laboratory strain engaged more in
      cannibalism than those of the field strain, both in agreement with our ideas. We
      hypothesize that the difference in cannibalism between the two genders will
      increase when they have the alternative to disperse.

PMID- 29470782
TI  - Treatment of Hepatitis C during Pregnancy-Weighing the Risks and Benefits in
      Contrast to HIV.
AB  - PURPOSE OF REVIEW: Increasing hepatitis C virus (HCV) cases over the past decade
      have raised concerns about subsequent increased cases in infants due to mother to
      child transmission (MTCT). Many are reminded of the early days of HIV and the
      rationale for using antiretroviral agents during pregnancy. RECENT FINDINGS:
      Direct-acting antivirals (DAAs) that are highly potent, all-oral, short-duration
      regimens that cure HCV have led many to consider what it would entail to use DAAs
      for pregnant women. Considering HIV and Hepatitis B virus (HBV) as two infections
      with MTCT to draw lessons from, DAA use to interrupt HCV MTCT comes with risks,
      costs, and many potential benefits. When considering how to effectively curb the
      current epidemic of HCV in the US population, using DAAs to treat pregnant women
      with HCV offers potential benefits to the mother immediately, to the pair in the
      short-term and to the child, family, and society over a lifetime.

PMID- 29470783
TI  - The Economic Foundations of Cohabiting Couples' Union Transitions.
AB  - In recent decades, cohabitation has become an increasingly important relationship
      context for U.S. adults and their children, a union status characterized by high
      levels of instability. To understand why some cohabiting couples marry but others
      separate, researchers have drawn on theories emphasizing the benefits of
      specialization, the persistence of the male breadwinner norm, low income as a
      source of stress and conflict, and rising economic standards associated with
      marriage (the marriage bar). Because of conflicting evidence and data
      constraints, however, important theoretical questions remain. This study uses
      survival analysis with prospective monthly data from nationally representative
      panels of the Survey of Income and Program Participation from 1996-2013 to test
      alternative theories of how money and work affect whether cohabiting couples
      marry or separate. Analyses indicate that the economic foundations of cohabiting
      couples' union transitions do not lie in economic specialization or only men's
      ability to be good providers. Instead, results for marriage support marriage bar
      theory: adjusting for couples' absolute earnings, increases in wealth and
      couples' earnings relative to a standard associated with marriage strongly
      predict marriage. For dissolution, couples with higher and more equal earnings
      are significantly less likely to separate. Findings demonstrate that within
      couple earnings equality promotes stability, and between-couple inequalities in
      economic resources are critical in producing inequalities in couples'
      relationship outcomes.

PMID- 29470784
TI  - Identification of Novel Autophagy Inhibitors via Cell-Based High-Content
      Screening.
AB  - Autophagy is a fundamental cellular catabolic pathway mediating the recycling of
      cellular components. Autophagy has been implicated in pathogenesis of diverse
      diseases such as neurodegeneration and cancer. Due to the therapeutic potential,
      the autophagy-modulating agents have profoundly enriched the spectrum of tools
      used to investigate autophagy. However, many of these compounds have additional
      off-target effects that may confound elucidation of autophagy in certain
      contexts. There remains high demand for highly specific and novel chemotypes that
      can be used to study the regulation mechanism of autophagy and contribute novel
      pharmacophores for therapeutic purposes. Here, we describe a cell-based
      quantitative high-content screening (HCS) for autophagy inhibitors using a human
      breast adenocarcinoma MCF7 cell line stably expressing EGFP-LC3, a bona fide
      marker of autophagy.

PMID- 29470786
TI  - Enzyme-modified indium tin oxide microelectrode array-based electrochemical uric
      acid biosensor.
AB  - We fabricated a miniaturized electrochemical uric acid biosensor with a 3
      aminopropyltriethoxysilane (APTES)-modified indium tin oxide (ITO) microelectrode
      array (MUEA). The ITO-MUEA on a glass plate was immobilized with the enzyme
      uricase, through a cross-linker, bis[sulfosuccinimidyl]suberate (BS3). The enzyme
      immobilized electrode (uricase/BS3/APTES/ITO-MUEA/glass) was characterized by
      atomic force microscopy and electrochemical techniques. The cyclic voltammetry
      and impedance studies show an effective binding of uricase at the MUEA surface.
      The amperometric response of the modified electrode was measured towards uric
      acid concentration in aqueous solution (pH 7.4), under microfluidic channel made
      of polydimethylsiloxane. The MUEA biosensor shows a linear response over a
      concentration range of 0.058 to 0.71 mM with a sensitivity of 46.26 MUA mM-1 cm
      2. A response time of 40 s reaching a 95% steady-state current value was
      obtained. The biosensor retains about 85% of enzyme activity for about 6 weeks.
      The biosensor using MUEA instead of a large single band of electrode allows the
      entire core of the channel to be probed though keeping an improved sensitivity
      with a small volume of sample and reagents.

PMID- 29470785
TI  - The Abscopal Effect in the Era of Cancer Immunotherapy: a Spontaneous Synergism
      Boosting Anti-tumor Immunity?
AB  - Radiotherapy is one of the main treatment strategies used in cancer. Aside from
      the local control of the disease, which is mediated by a direct cytotoxic effect
      on tumor cells, radiotherapy has also been shown to exert immune-mediated local
      and systemic effects. Radiotherapy can elicit anti-tumor responses in distant
      sites from the radiation field; this phenomenon is known as the abscopal effect
      and has been described in patients previously treated with immune checkpoint
      blockade (ICB). Considering that the efficacy of immunotherapy has been
      demonstrated only in a subset of patients-who often benefit with lasting
      responses-efforts are ongoing to potentiate its activity with the development of
      new combination strategies. Radiotherapy might represent a potential candidate
      for a synergistic combination with immunotherapy, by improving the immunogenicity
      of tumors and by enhancing local and systemic immune effects. This review aims to
      summarize the current pre-clinical and clinical data on the immune effects of
      radiotherapy and their potential implications for cancer immunotherapy.

PMID- 29470787
TI  - Arterial Stiffness and Vascular Aging: From Pathophysiology to Treatment, with a
      Look at the Future.

PMID- 29470788
TI  - Commentary: Using Impedance Cardiography to Detect Asymptomatic Cardiovascular
      Disease in Prehypertensive Adults with Risk Factors.
AB  - New guidelines on hypertension eliminated the classification of prehypertension
      and divided those blood pressure (BP) levels into elevated BP and stage 1
      hypertension. For elevated BP, this study showed that cardiovascular (CV)
      abnormalities were prevalent in adults over 40 years of age with at least 2 CV
      risk factors. Detecting abnormalities of the CV system moves a patient from being
      at high risk to having earlystage cardiovascular disease (CVD) and supports a
      decision to treat. By redefining stage 1 and lowering the target BP, the new
      guidelines have set an ambitious goal for early intervention to prevent
      progression of CVD. Proper drug selection and titration are critical.
      Hypertensive patients have diverse CV abnormalities that can be quantified by
      impedance cardiography. By stratifying patients with ventricular, vascular, and
      hemodynamic abnormalities, treatment can be customized based on the abnormal
      underlying mechanisms to rapidly control BP and prevent progression of CVD.

PMID- 29470789
TI  - Evaluation of Psychometric and Linguistic Properties of the Italian Adolescent
      Pain Assessment Scales: A Systematic Review.
AB  - INTRODUCTION: Adolescents' pain experiences are complex and multidimensional, and
      evaluating pain only from a sensory and affective point of view may be in many
      instances limiting and inadequate; this is the reason why it is of paramount
      importance to identify the tools which can better assess the pain experienced by
      young patients. A person-oriented approach is highly encouraged, as it may better
      investigate the cognitive and behavioral development typical of this age group.
      The aim of this review paper is to describe the available tools which are able to
      adequately assess pain intensity in adolescents, in particular those validated in
      Italian. METHODS: We conducted a systematic review using four databases: CINAHL,
      PsycINFO, PubMed and Cochrane, and selected all the articles published between
      January 1970 and November 2017. We selected all the papers reporting the
      validation process of pain assessment tools specifically tailored for adolescent
      patients (age range 10-18 years) and based on psychometric and linguistic
      parameters, and focused especially on the tools available in Italian and able to
      measure acute and chronic pain. RESULTS: The results of our investigation have
      revealed the existence of 40 eligible tools, 17 of which are monodimensional and
      the remaining 23 multidimensional, more specifically tailored to assess both
      acute and chronic pain. Some of the instruments (26) were self-reports while
      others were classified as behavioral (13) and/or mixed. Only one tool turned out
      to be suitable for fragile adolescents, while six adopted a person-oriented
      approach that better emphasized the cognitive and behavioral process typical of
      the adolescent population. None of them has ever been validated in Italian.
      CONCLUSION: Valid and reliable psychometric tools specifically organized to
      provide a cultural and linguistic evaluation of the patient are indeed the most
      recommended instruments to assess the intensity of the pain experienced by the
      patient, as they may provide useful information to implement a health policy
      aimed at identifying the best assistance programs.

PMID- 29470790
TI  - Magnesium corrosion particles do not interfere with the immune function of
      primary human and murine macrophages.
AB  - Magnesium is currently under investigation as a prospective biodegradable implant
      material. Biodegradation of magnesium causes a release of magnesium, hydroxide
      ions and hydrogen gas but it can also lead to the formation of particulate
      debris. Implant-derived particles may have immunotoxic effects. To investigate
      the influence of magnesium-derived particles on the immune functions of primary
      macrophages, up to 500 MUg/ml magnesium or magnesium corrosion particles were
      added to the cell culture medium. No major effects were observed on cell
      viability and on the release of the proinflammatory cytokine tumor necrosis
      factor (TNF)alpha. In addition, the ability of macrophages to stimulate
      proliferation of allogenic lymphocytes in a mixed leukocyte reaction remained
      unaffected. When macrophages were incubated with magnesium particles and then
      infected with the apathogenic Mycobacterium smegmatis, infection-induced TNFalpha
      secretion from murine macrophages was inhibited but not from human macrophages.
      However, the bactericidal activity of either cell type was not influenced. In
      conclusion, magnesium-related particles did not restrict the immune function of
      macrophages, suggesting that magnesium implants and corrosion particles derived
      thereof are highly biocompatible and have a low inflammatory potential.

PMID- 29470791
TI  - Development of microspheres for biomedical applications: a review.
AB  - An overview of microspheres manufactured for use in biomedical applications based
      on recent literature is presented in this review. Different types of glasses
      (i.e. silicate, borate, and phosphates), ceramics and polymer-based microspheres
      (both natural and synthetic) in the form of porous , non-porous and hollow
      structures that are either already in use or are currently being investigated
      within the biomedical area are discussed. The advantages of using microspheres in
      applications such as drug delivery, bone tissue engineering and regeneration,
      absorption and desorption of substances, kinetic release of the loaded drug
      components are also presented. This review also reports on the preparation and
      characterisation methodologies used for the manufacture of these microspheres.
      Finally, a brief summary of the existing challenges associated with processing
      these microspheres which requires further research and development are presented.

PMID- 29470792
TI  - Assessment of injectable and cohesive nanohydroxyapatite composites for
      biological functions.
AB  - Pressing need for utilization of injectables/fillers in various forms of
      orthopaedic treatments/surgeries commands an equal demand for better graft
      material. Injectable bone graft material based on biomimetically synthesized
      nanohydroxyapatite was developed and subjected to ball milling for different
      times; three materials thus produced were evaluated for their biological
      properties. The three composites tested were found to have some difference in
      proliferation and differentiation on mesenchymal stem cells in cultures. In vivo
      studies were performed by implanting the graft materials with or without cells in
      the bone drill hole injury created in the femur of Wistar rats. Our studies show
      that the composites lead to well-healed injury site with normal histology without
      inflammation or fibrous tissue formation and bone deformity. This material needs
      to be tested on large animals for further ascertaining its applicability in
      clinical use.

PMID- 29470793
TI  - Designing casein-coated iron oxide nanostructures (CCIONPs) as superparamagnetic
      core-shell carriers for magnetic drug targeting.
AB  - Magnetic drug targeting is a drug delivery system applicable to cancer treatment.
      Coated magnetic particles, called carriers, are very useful for delivering
      chemotherapeutic drugs. In the present research, casein-coated iron oxide
      nanocarriers (CCIONPs) of core shell nanostructure have been described as being
      applicable to magnetic drug targeting. The structure, morphology, and composition
      of prepared magnetic nanoparticles were determined by analytical techniques like
      Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy
      (TEM), scanning electron microscopy (SEM), Electron diffraction (ED), X-ray
      diffraction (XRD), Zeta potential, Dynamic light scattering (DLS), Mossbauer and
      Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), Vibrating sample
      magnetometery (VSM)) and in vitro cytotoxicity analysis. Magnetization studies of
      CCIONPs conducted at room temperature using a vibrating sample magnetometer
      suggested their superparamagnetic nature as having a saturation magnetization
      (Ms) of 64 emu g-1 at an applied magnetic field of 5 kOe. The size of the
      magnetic polymeric nanoparticles was found to lie in the range of 73.9 +/-0.36
      nm, and the particles exhibited superparamagnetic behavior. The prepared
      particles could be used as a drug carrier for controlled and targeted drug
      delivery.

PMID- 29470794
TI  - Erratum to: Injectable scaffold as minimally invasive technique for cartilage
      tissue engineering: in vitro and in vivo preliminary study.

PMID- 29470795
TI  - Assessment of lactoferrin-conjugated solid lipid nanoparticles for efficient
      targeting to the lung.
AB  - The aim of the present study was to develop a target oriented drug delivery
      system for the lungs. Lactoferrin (Lf)-coupled solid lipid nanoparticles (SLNs)
      bearing rifampicin was prepared by a solvent injection method. The prepared
      nanoparticles were characterized for shape, particle size, polydispersity and
      percentage drug entrapment. An optimized formulation was then studied for its in
      vivo performance in animals and to determine its targeting efficiency. It was
      observed that, upon coupling with Lf, the size of SLNs increased while the
      percent entrapment efficiency decreases. In in vitro release, determined by a
      dialysis technique, analysis showed that uncoupled SLNs exhibited higher drug
      release as compared to coupled SLNs. An in vivo biodistribution study shows 47.7
      +/-0.4 drug uptakes by the lungs, which was 3.05 times higher in comparison to
      uncoupled SLNs. These biodistribution studies are further supported by the
      fluorescence study that revealed enhanced uptake of Lf-coupled SLNs in the lung.
      From the presented results, it can be concluded that Lf-coupled SLNs enhanced
      drug uptake in the lung. Moreover, lactoferrin is an efficient molecule that can
      be used for targeting active agents directly to the lung.

PMID- 29470796
TI  - Peers influence adolescent reward processing, but not response inhibition.
AB  - Most adolescent risk taking occurs in the presence of peers. Prior research
      suggests that peers alter adolescents' decision making by increasing reward
      sensitivity and the engagement of regions involved in the processing of rewards,
      primarily the striatum. However, the potential influence of peers on the capacity
      for impulse control, and the associated recruitment of the brain's control
      circuitry, has not yet been adequately examined. In the current study,
      adolescents underwent functional neuroimaging while they completed interleaved
      rounds of risk-taking and response-inhibition tasks. Social context was
      manipulated such that the participants believed they were either playing alone
      and unobserved, or watched by an anonymous peer. Compared to those who completed
      the tasks alone, adolescents in the peer condition took more risks during the
      risk-taking task and exhibited relatively heightened activation of the striatum.
      Activity within this striatal region also predicted individual differences in
      overall risk taking. In contrast, the presence of peers had no effect on
      behavioral response inhibition and had minimal impact on the engagement of
      typical cognitive control regions. In a subregion of the anterior insula engaged
      mutually by both tasks, activity was again found to be sensitive to social
      context during the risk-taking task, but not during the response-inhibition task.
      These findings extend the evidence that the presence of peers biases adolescents
      towards risk taking by increasing reward sensitivity rather than disrupting
      cognitive control.

PMID- 29470797
TI  - Body mass index is independently associated with xanthine oxidase activity in
      overweight/obese population.
AB  - PURPOSE: The pathophysiological mechanism of the relationship between xanthine
      oxidase (XO) activity and obesity has not been completely elucidated. Since
      inflammation and oxidative stress are regarded as key determinants of enlarged
      adipose tissue, we aimed to investigate the association between oxidative stress
      (as measured with XO activity), inflammation [as measured with high-sensitivity C
      reactive protein (hsCRP)] and obesity [as measured with body mass index (BMI)].
      In addition, we wanted to examine whether hsCRP itself plays an independent role
      in XO activity increase or it is only mediated through obesity. METHODS: A total
      of 118 overweight/obese volunteers (mean age 54.76 +/- 15.13 years) were included
      in the current cross-sectional study. Anthropometric, biochemical parameters, and
      blood pressure were obtained. RESULTS: Significant differences between age, BMI,
      waist circumference, concentrations of uric acid and hsCRP, as well as xanthine
      dehydrogenase (XDH) activities were evident among XO tertile groups. Multiple
      linear regression analysis revealed that BMI (beta = 0.241, p = 0.012) and XDH
      (beta = - 0.489, p < 0.001) are the independent predictors of XO activity (R2
      adjusted = 0.333), whereas hsCRP lost its independent role in XO activity
      prediction. CONCLUSION: Obesity (as determined with increased BMI) is an
      independent predictor of high XO activity in overweight/obese population. LEVEL
      OF EVIDENCE: Level V: cross-sectional descriptive study.

PMID- 29470798
TI  - NR4A1 contributes to high-fat associated endothelial dysfunction by promoting
      CaMKII-Parkin-mitophagy pathways.
AB  - Parkin-related mitophagy is vital for endothelial cell viability and the
      development of atherosclerosis, although the upstream regulatory factor
      underlying Parkin-mediated mitophagy in endothelial apoptosis and atherosclerosis
      progression remains unknown. In the present study, we demonstrated that nuclear
      receptor subfamily 4 group A member 1 (NR4A1) is actually expressed in aortic
      endothelial cells (AECs) under oxidized low-density lipoprotein (ox-LDL)
      treatment in vitro or isolated from high-fat treated mice in vivo. Higher NR4A1
      levels were associated with AEC apoptosis, mitochondrial dysfunction, and energy
      disorder. At the molecular level, ox-LDL stimulation increased NR4A1 expression,
      which evoked Parkin-mediated mitophagy. Excessive mitophagy overtly consumed
      mitochondrial mass, leading to an energy shortage and mitochondrial dysfunction.
      However, loss of NR4A1 protected AECs against ox-LDL induced apoptosis by
      inhibiting excessive mitophagy. Furthermore, we also identified that NR4A1
      regulated Parkin activation via post-transcriptional modification by
      Ca2+/calmodulin-dependent protein kinase II (CaMKII). Activated CaMKII via NR4A1
      induced the phosphorylated activation of Parkin. In summary, our data support the
      role of NR4A1/CaMKII/Parkin/mitophagy in AEC apoptosis and atherosclerosis
      formation and provide new insights into treating atherosclerosis with respect to
      endothelial viability, mitophagy, and NR4A1.

PMID- 29470800
TI  - Landiolol: A Review in Tachyarrhythmias.
AB  - Intravenous landiolol [Rapibloc(r) (EU)], an ultra short-acting highly
      cardioselective beta1-blocker, is approved in the EU for the rapid short-term
      control of tachyarrhythmias in the perioperative and intensive care settings. It
      has long been used in Japan to treat perioperative tachyarrhythmias. The efficacy
      of landiolol has been demonstrated in a large number of randomized controlled
      clinical trials. Landiolol significantly reduced heart rate in patients with
      postoperative or intraoperative supraventricular tachycardia relative to placebo
      and in those with atrial fibrillation/flutter and left ventricular dysfunction
      relative to digoxin. It was more effective than diltiazem in converting
      postoperative atrial fibrillation (POAF) to normal sinus rhythm. Perioperative
      prophylactic administration of landiolol significantly reduced the incidence of
      POAF during the first week after cardiac and other surgeries, compared with
      diltiazem, placebo or no landiolol treatment. Landiolol also attenuated adverse
      haemodynamic and other responses to invasive procedures such as percutaneous
      coronary intervention, tracheal intubation, extubation and electroconvulsive
      therapy. Landiolol was generally well tolerated, with a relatively low risk of
      hypotension and bradycardia. Landiolol has more favourable pharmacological
      properties than esmolol, a short-acting beta-blocker commonly used for the rapid
      control of heart rate. Although additional comparative studies are warranted to
      define the place of landiolol relative to esmolol, current evidence suggest that
      landiolol is a useful option for the rapid short-term control of
      tachyarrhythmias. Landiolol offers a simple dosage scheme and is available in two
      easy-to-use formulations (concentrate and powder).

PMID- 29470799
TI  - An Intervention Framework for Institutions to Meet New ACGME Common Program
      Requirements for Physician Well-Being.

PMID- 29470801
TI  - Episodic Breathlessness in Patients with Advanced Cancer: Characteristics and
      Management.
AB  - The aim of this review is to present the way in which episodic breathlessness
      (EB) has been recognized over the years, with regard to definition,
      characteristics, and management of these acute episodes that have serious
      consequences for patients. EB is characterized by a sudden increase in intensity
      of dyspnea over a short duration of time, leading to high levels of anxiety. A
      significant aggravation of dyspnea may occur in patients with a background of
      dyspnea or intermittently even without basal breathlessness. Often, known
      precipitating factors may trigger EB. Flares of breathlessness are accompanied by
      degrees of psychological distress, although it is unclear whether psychological
      factors may precede or be induced by EB. In any case, there is a reinforcing
      circuit. The duration of EB ranges from 10-30 min. Given the specific temporal
      pattern, requiring rapid intervention, substances with a short onset of action
      are suitable to overlap this phenomenon. Short-onset opioids could provide a
      clinical effect overlapping the onset and duration of an episode, resembling what
      has been largely reported for breakthrough pain. Although data are still
      insufficient to suggest specific recommendations, strategies such as avoiding
      exertion, pacing or using devices, or keeping calm have been described. Few
      controlled studies have investigated the effects of different formulations of
      opioids. Some data were gathered from studies assessing the pre-emptive use of
      rapid onset opioids, such as transmucosal preparations of fentanyl, followed by a
      provocative test, while other studies attempted to reproduce real-life
      conditions, given as needed. All these trials were insufficiently powered to
      address the efficacy of fentanyl products over oral morphine or placebo,
      reflecting the difficulties in patient recruiting and finalizing the studies.
      Strategies to prevent the occurrence of EB should be taken into consideration,
      including optimization of the condition of persistent dyspnea or treating
      psychologic or environmental causes.

PMID- 29470802
TI  - Male Undergraduates' HPV Vaccination Behavior: Implications for Achieving HPV
      Associated Cancer Equity.
AB  - Despite the availability of the human papillomavirus (HPV) vaccine for males,
      uptake of the vaccine has been low, particularly among young adult males. This
      study aimed to investigate the levels of HPV vaccination and predictors of HPV
      vaccine completion in college men ages 18-26. We analyzed data from the 2015
      College Student Health Survey, which was administered at 17 post-secondary
      institutions in Midwest areas. We included only responses from male participants
      who were ages 18-26 years old, resulting in a sample size of 2516. We used
      Andersen's Behavioral Model of Health Services Utilization to guide our study
      design. Multivariate logistic regression was used to examine predictors of HPV
      vaccine receipt. College-aged males in our sample had a HPV vaccine completion
      rate of 50.0%. Male students who were younger, had at least one parent who held a
      graduate degree, had initiated sex, and were enrolled at a private 4-year
      institution were more likely to have been vaccinated. These findings suggest that
      HPV vaccination in college-aged men are low. Efforts are needed to increase HPV
      vaccination in male students who are older, from lower socioeconomic statuses,
      have not initiated sex, and enrolled at public institutions. Findings also
      indicate important gender disparities in vaccine uptake that must be addressed in
      order to achieve optimal vaccine uptake in college-aged males.

PMID- 29470803
TI  - Correction to: Chronic Granulomatous Disease in a Brazilian Patient Mimetizing
      Sarcoidosis.
AB  - The original version of abstract PO-162 "Chronic Granulomatous Disease in a
      Brazilian Patient Mimetizing Sarcoidosis" incorrectly listed the name of the
      second author as Micheli Barsioti. The correct spelling of the author's name is
      Michele Baziotti Man.

PMID- 29470804
TI  - Effects of physical exercise on breast cancer-related secondary lymphedema: a
      systematic review.
AB  - PURPOSE: The aim of this systematic review is to assess the effect of different
      types of exercise on breast cancer-related lymphedema (BCRL) in order to
      elucidate the role of exercise in this patient group. METHODS: A systematic data
      search was performed using PubMed (December 2016). The review is focused on the
      rehabilitative aspect of BCRL and undertaken according to the PRISMA statement
      with Levels of Evidence (LoE) assessed. RESULTS: 11 randomized controlled trials
      (9 with LoE 1a and 2 with LoE 1b) that included 458 women with breast cancer in
      aftercare were included. The different types of exercise consisted of aqua lymph
      training, swimming, resistance exercise, yoga, aerobic, and gravity-resistive
      exercise. Four of the studies measured a significant reduction in BCRL status
      based on arm volume and seven studies reported significant subjective
      improvements. No study showed adverse effects of exercise on BCRL. CONCLUSION:
      The evidence indicates that exercise can improve subjective and objective
      parameters in BCRL patients, with dynamic, moderate, and high-frequency exercise
      appearing to provide the most positive effects.

PMID- 29470805
TI  - Adjuvant versus neoadjuvant chemotherapy in triple-negative breast cancer
      patients with BRCA mutations.
AB  - PURPOSE: As triple-negative breast cancers are associated with earlier
      recurrences and poorer survival, optimal treatment of early-stage breast cancer
      is essential. Several retrospective studies in triple-negative breast cancer have
      reported conflicting results in overall survival in patients receiving
      neoadjuvant or adjuvant systemic therapy. This study aims to analyze outcomes of
      adjuvant versus neoadjuvant in patients with early-stage triple-negative breast
      cancer with and without BRCA germline mutations. METHODS: Patients with stage I
      or II triple-negative breast cancer who had BRCA testing were identified from a
      prospective cohort study of 4027 patients. Clinical, demographic, genetic test
      results, chemotherapy, recurrence, and survival data were analyzed. Overall
      survival and disease-free survival were estimated using the Kaplan-Meier method.
      RESULTS: 319 patients with stage I and II triple-negative breast cancer who met
      eligibility criteria were included in the analysis. 187 received adjuvant
      chemotherapy (58.6%) and 132 received neoadjuvant chemotherapy (41.4%). 135 were
      BRCA positive (42.3%) and 184 were BRCA negative (57.7%). There was no
      significant association between overall survival or disease-free survival and
      treatment with neoadjuvant versus adjuvant in the overall cohort. Furthermore,
      there were no significant differences between patient subgroups (neoadjuvant BRCA
      positive, neoadjuvant BRCA negative, adjuvant BRCA positive, and adjuvant BRCA
      negative) with respect to either overall survival or disease-free survival.
      CONCLUSIONS: Neoadjuvant versus adjuvant with standard anthracycline- and taxane
      containing regimens results in similar disease-free survival and overall survival
      among patients with stage I and II triple-negative breast cancer regardless of
      BRCA status. Further studies are needed to evaluate whether similar results are
      observed with newer agents.

PMID- 29470806
TI  - Screening of over 1000 Indian patients with breast and/or ovarian cancer with a
      multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations.
AB  - PURPOSE: Breast and/or ovarian cancers are among the most common cancers in women
      across the world. In the Indian population, the healthcare burden of breast
      and/or ovarian cancers has been steadily rising, thus stressing the need for
      early detection, surveillance, and disease management measures. However, the
      burden attributable to inherited mutations is not well characterized. METHODS: We
      sequenced 1010 unrelated patients and families from across India with an
      indication of breast and/or ovarian cancers, using the TruSight Cancer panel
      which includes 14 genes, strongly associated with risk of hereditary breast
      and/or ovarian cancers. Genetic variations were identified using the StrandNGS
      software and interpreted using the StrandOmics platform. RESULTS: We were able to
      detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A
      majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared
      to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at
      diagnosis and family history of cancer, the high rate of 75% of detection of
      hereditary variants was observed in patients whose age at diagnosis was below 40
      years and had first-degree family member(s) affected by breast and/or ovarian
      cancers. Our findings indicate that in the Indian population, there is a high
      prevalence of mutations in the high-risk breast cancer genes: BRCA1, BRCA2, TP53,
      and PALB2. CONCLUSION: In India, socioeconomic inequality limiting access to
      treatment is a major factor towards increased cancer burden; therefore,
      incorporation of a cost-effective and comprehensive multi-gene test will be
      helpful in ensuring widespread implementation of genetic screening in the
      clinical practice for hereditary breast and/or ovarian cancers.

PMID- 29470807
TI  - Longitudinal Effects of Adjuvant Endocrine Therapy on the Quality of Life of Post
      menopausal Women with Non-metastatic ER+ Breast Cancer: A Systematic Review.
AB  - BACKGROUND: Anti-estrogen (ER) endocrine therapy is an effective treatment
      strategy in reducing breast cancer mortality. This therapy has a better
      therapeutic index than chemotherapy but can still affect patients' quality of
      life (QOL) over time. OBJECTIVE: The objectives of this systematic review were to
      (1) describe QOL instruments used in ER-positive (ER+) non-metastatic breast
      cancer trials and (2) document the longitudinal effects of adjuvant endocrine
      therapy on the QOL of post-menopausal women with ER+ non-metastatic breast
      cancer. METHODS: We searched three electronic bibliographic databases for
      articles published from inception to October 2017 that described (1) a randomized
      controlled trial (RCT) of non-metastatic breast cancer containing an adjuvant
      endocrine regimen in at least one arm; (2) the use of a patient self-report
      measure assessing general or breast cancer-specific QOL; and (3) QOL outcomes at
      multiple time points during follow-up of at least 5 years. All included trials
      were independently evaluated by two reviewers, and data were extracted using
      standardized forms. RESULTS: In total, 13 studies met our inclusion criteria and
      were assessed in this review. The quality of the trials was reasonably good. The
      top three most commonly used QOL instruments in the trials were the Functional
      Assessment of Cancer Therapy/Functional Assessment of Chronic Illness Therapy,
      the Short Form-36 and the Menopause-Specific Quality of Life. Most studies found
      no differences between tamoxifen and aromatase inhibitor groups in terms of
      global QOL. QOL data affected treatment regimen recommendations in a few cases. A
      meta-analysis was not feasible because the RCTs included in our review varied in
      terms of sample size, comparators, QOL instrument used, and timing of QOL
      measurement. Additionally, as no search strategy has perfect sensitivity,
      specificity and accuracy, there is always a chance that potentially relevant
      articles were missed. CONCLUSION: This systematic review suggests that the QOL of
      post-menopausal women is unlikely to be adversely affected by long-term use of
      adjuvant endocrine therapy. Efforts are needed to improve the quality of QOL
      reporting in clinical trials.

PMID- 29470808
TI  - Comparative Analysis of Recruitment Strategies in a Study of Men Who Have Sex
      with Men (MSM) in Metropolitan Detroit.
AB  - HIV/AIDS-related research requires recruitment of representative samples of MSM;
      yet, we know little about the comparative yield, diversity and cost-benefit
      tradeoffs between different recruitment venues. We compared 11 recruitment venues
      used for nine HIV prevention-related focus groups with MSM in Metropolitan
      Detroit. Of the 64 participants, 24 were clients recruited via an HIV/AIDS
      focused nonprofit, 20 from Grindr advertisements, 6 from university-student email
      lists, and 5 from flyers/palmcards. Significantly more African-American, low
      income and HIV-positive participants were recruited via the nonprofit. The best
      cost-benefit tradeoffs were for organizational Facebook posts, email groups,
      personal networking, and nonprofit recruitment. Grindr increased the size of the
      sample, though at greater expense. Facebook and Scruff advertisements and gay bar
      outreach represented greater costs than benefits. Only 11.6% of Grindr
      respondents attended the focus groups. A mix of online and offline recruitment
      venues can generate a large and diverse sample of MSM, but venue performance is
      uneven.

PMID- 29470810
TI  - Diversity of Anopheles spp. (Diptera: Culicidae) in an Amazonian Urban Area.
AB  - The genus Anopheles encompasses several species considered as vectors of human
      infecting Plasmodium. Environmental changes are responsible for behavior changes
      in these vectors and therefore the pattern of malaria transmission. To better
      understand the dynamics of malaria transmission, this study aimed at identify the
      species of adult anophelines found in a malaria endemic urban area of the Amazon
      region, Mancio Lima, located in the Acre State Brazil. Using Shannon-type light
      traps installed at 11 collection points near fish ponds, a total of 116
      anophelines were collected belonging to nine species. Anopheles darlingi Root
      1926 and An. albitarsis s.l. Lynch-Arribalzaga 1878 were the most abundant and
      predominant species. Despite the low number of captured adult anophelines, the
      occurrence of An. darlingi throughout all urban area and the presence of
      secondary vectors reinforce the need of a permanent and continuous entomological
      surveillance.

PMID- 29470811
TI  - Correction to: The Genus Coccidella Hambleton (Hemiptera: Rhizoecidae) with
      Description of Two New Species.
AB  - Due to an unfortunate turn of events, the initials of the third author appeared
      incorrectly in the original publication as the name should have read T Kondo.

PMID- 29470809
TI  - Receiving HIV Serostatus Disclosure from Partners Before Sex: Results from an
      Online Survey of Chinese Men Who Have Sex with Men.
AB  - HIV serostatus disclosure before sex can facilitate serosorting, condom use and
      potentially decrease the risk of HIV acquisition. However, few studies have
      evaluated HIV serostatus disclosure from partners before sex. We examined the
      rate and correlates of receiving HIV serostatus disclosure from regular and
      casual male partners before sex among an online sample of men who have sex with
      men (MSM) in China. An online cross-sectional study was conducted among MSM in
      eight Chinese cities in July 2016. Participants completed questions covering
      sociodemographic information, sexual behaviors, HIV testing (including HIV self
      testing) history, self-reported HIV status, and post-test violence. In addition,
      participants were asked whether they received HIV serostatus disclosure from
      their most recent partners before sex. Overall, 2105 men completed the survey.
      Among them, 85.9% were never married, and 35.4% had high school or less
      education. A minority (20.6%, 346/1678; 17.8%, 287/1608) of men received HIV
      serostatus disclosure from their most recent regular and casual male partners,
      respectively. Multivariate analysis indicated that participants who ever self
      tested for HIV were more likely to have received HIV status disclosure from
      regular [adjusted OR (aOR) = 1.92, 95% CI 1.50-2.44] and casual (aOR = 2.34, 95%
      CI 1.80-3.04) male partners compared to never self-tested participants. Compared
      to participants who had not received HIV status disclosure from regular partners,
      participants who received disclosure from regular male partners had higher
      likelihood in experiencing post-test violence (aOR = 5.18, 95% CI 1.53-17.58).
      Similar results were also found for receiving HIV serostatus disclosure from
      casual partners. This study showed that HIV serostatus disclosure from partners
      was uncommon among Chinese MSM. Interventions and further implementation research
      to facilitate safe disclosure are urgently needed for MSM.

PMID- 29470812
TI  - Lumbosacral polyradiculopathy after intrathecal chemotherapy in pediatric acute
      lymphoblastic leukemia.

PMID- 29470813
TI  - Structural and Socio-cultural Barriers to Prenatal Care in a US Marshallese
      Community.
AB  - Objectives Pacific Islanders are disproportionately burdened by poorer perinatal
      health outcomes with higher rates of pre-term births, low birth weight babies,
      infant mortality, and inadequate or no prenatal care. The aim of this study is to
      examine Marshallese mothers' beliefs, perceptions, and experiences of prenatal
      care and to identify potential barriers. Methods Three focus groups were
      conducted with Marshallese mothers, who were 18 years or older, and living in
      Arkansas. Focus groups focused on mothers' beliefs, perceptions, and experiences
      of prenatal care. A thematic qualitative analysis was conducted to identify
      salient themes within the data. Results The results demonstrated that negotiating
      health insurance, transportation, and language barriers were all major structural
      barriers that constrain prenatal care. The social-cultural barriers that emerged
      included a lack of understanding of the importance of seeking early and
      consistent prenatal care, as well as how to navigate the healthcare process. The
      more complicated challenges that emerged were the feelings of shame and
      embarrassment due to the perception of their age or being unmarried during
      pregnancy not being acceptable in American culture. Furthermore, the participants
      described perceived discrimination from prenatal care providers. Lastly, the
      participants described fear as a barrier to seeking out prenatal care.
      Conclusions for Practice This study identified both structural and socio-cultural
      barriers that can be incorporated into suggestions for policy makers to aid in
      alleviating maternal health disparities among Pacific Islander women. Further
      research is needed to address the Marshallese mothers' perceived discrimination
      from maternal health care providers.

PMID- 29470814
TI  - Continuing Professional Development in Maternal Health Care: Barriers to Applying
      New Knowledge and Skills in the Hospitals of Rwanda.
AB  - Objectives Training healthcare professionals in emergency maternal healthcare is
      a critical component of improving overall maternal health in developing countries
      like Rwanda. This paper explored the challenges that healthcare professionals who
      participated in a Continuing Professional Development (CPD) program on Advanced
      Life Support in Obstetrics(r) (ALSO) face in putting the learned knowledge and
      skills into practice in hospitals of Rwanda. Methods This study used a mixed
      methods approach to understand the challenges/barriers to applying new knowledge
      and skills in the hospitals of Rwanda. We conducted thirteen purposive in-depth
      interviews with ALSO(r) trainees (nurses, midwives and physicians) complemented
      with a cross-sectional survey on staff turnover in eight of the nine hospitals in
      the Eastern province of Rwanda. Results Our study found that trainees do not get
      enough opportunity to apply the new knowledge and skills in their hospitals and
      expand to health centers. In part because they are frequently rotating to
      different departments of the hospital and are not getting the opportunity to
      train their colleagues to share the learned knowledge and skills. The lack of
      refresher trainings/mentorship and the high personnel turnover were also reported
      as a barrier to applying new knowledge and skills. Reasons for staff turnover
      included pursuing further studies, a better opportunity (job/remuneration), low
      morale, and family related motives including joining a spouse or better schools
      for children. Conclusions for Practice Expanding and formalizing CPD training to
      all the healthcare professionals involved in providing maternal care services
      would improve the provision of emergency maternal healthcare in Rwanda.

PMID- 29470815
TI  - Identification of miR-9 as a negative factor of insulin secretion from beta
      cells.
AB  - MicroRNA is a novel class of small noncoding RNA that has been implicated in a
      variety of physiological and pathological processes, including glucose
      homeostasis and diabetes mellitus. So far, a few studies have reported that
      miRNAs may be an important regulator in glucose-stimulated insulin secretion
      (GSIS) pathway. However, the role of miRNAs in this process remains unclear. The
      levels of miRNAs in mouse islets and MIN6 cells were determined by quantitative
      RT-PCR. Concentration of insulin was determined by ELISA, and the expression of
      the target protein was determined with western blot assay. The overexpression and
      downregulation of miRNAs in MIN6 were conducted using cell transfection methods.
      And luciferase assay was used to measure the direct interaction between miRNAs
      and target messenger RNAs 3'UTR. miR-9 was screened out for it was downregulated
      under the effects of short-term high glucose, while long-term high glucose
      relatively increased miR-9 expression. The Stxbp1 expression was decreased with
      the overexpression of miR-9 in MIN6 cells and increased when miR-9 was
      downregulated. Moreover, it was verified by luciferase assay that miR-9 regulated
      Stxbp1 gene expression by directly targeting Stxbp1 messenger RNA 3'UTR. This
      study suggests that the pathway consisting of miR-9 and Stxbp1 plays a key role
      in beta-cell function, thus contributing to the network of miRNA-insulin
      secretion and offering a new candidate for diabetes therapy.

PMID- 29470817
TI  - Capsule Commentary on Pilla et al., Predictors of Insulin Initiation in Patients
      with Type 2 Diabetes: an Analysis of the Look AHEAD Randomized Trial.

PMID- 29470816
TI  - Hepatic subcellular distribution of squalene changes according to the
      experimental setting.
AB  - Squalene is the main unsaponifiable component of virgin olive oil, the main
      source of dietary fat in Mediterranean diet, traditionally associated with a less
      frequency of cardiovascular diseases. In this study, two experimental approaches
      were used. In the first, New Zealand rabbits fed for 4 weeks with a chow diet
      enriched in 1% sunflower oil for the control group, and in 1% of sunflower oil
      and 0.5% squalene for the squalene group. In the second, APOE KO mice received
      either Western diet or Western diet enriched in 0.5% squalene for 11 weeks. In
      both studies, liver samples were obtained and analyzed for their squalene content
      by gas chromatography-mass spectrometry. Hepatic distribution of squalene was
      also characterized in isolated subcellular organelles. Our results show that
      dietary squalene accumulates in the liver and a differential distribution
      according to studied model. In this regard, rabbits accumulated in cytoplasm
      within small size vesicles, whose size was not big enough to be considered lipid
      droplets, rough endoplasmic reticulum, and nuclear and plasma membranes. On the
      contrary, mice accumulated in large lipid droplets, and smooth reticulum
      fractions in addition to nuclear and plasma membranes. These results show that
      the squalene cellular localization may change according to experimental setting
      and be a starting point to characterize the mechanisms involved in the protective
      action of dietary squalene in several pathologies.

PMID- 29470818
TI  - Variability in Predictions from Online Tools: A Demonstration Using Internet
      Based Melanoma Predictors.
AB  - BACKGROUND: Prognostic models are increasingly being made available online, where
      they can be publicly accessed by both patients and clinicians. These online tools
      are an important resource for patients to better understand their prognosis and
      for clinicians to make informed decisions about treatment and follow-up. The goal
      of this analysis was to highlight the possible variability in multiple online
      prognostic tools in a single disease. METHODS: To demonstrate the variability in
      survival predictions across online prognostic tools, we applied a single
      validation dataset to three online melanoma prognostic tools. Data on melanoma
      patients treated at Memorial Sloan Kettering Cancer Center between 2000 and 2014
      were retrospectively collected. Calibration was assessed using calibration plots
      and discrimination was assessed using the C-index. RESULTS: In this demonstration
      project, we found important differences across the three models that led to
      variability in individual patients' predicted survival across the tools,
      especially in the lower range of predictions. In a validation test using a single
      institution data set, calibration and discrimination varied across the three
      models. CONCLUSIONS: This study underscores the potential variability both within
      and across online tools, and highlights the importance of using methodological
      rigor when developing a prognostic model that will be made publicly available
      online. The results also reinforce that careful development and thoughtful
      interpretation, including understanding a given tool's limitations, are required
      in order for online prognostic tools that provide survival predictions to be a
      useful resource for both patients and clinicians.

PMID- 29470819
TI  - Adequate Local Control in High-Risk Soft Tissue Sarcoma of the Extremity Treated
      with Surgery Alone at a Reference Centre: Should Radiotherapy Still be a
      Standard?
AB  - BACKGROUND: Established practice for the management of soft tissue sarcoma (STS)
      of the extremity and trunk wall combines perioperative radiotherapy (RT) with
      limb-preserving surgery. OBJECTIVE: The aim of this study was to explore whether
      high-quality surgery at high-volume centers may offer equivalent local control in
      selected cases, when RT needs to be avoided. METHODS: All consecutive adult cases
      of primary, high-risk STSs treated in a high-volume reference center over a 12
      year timeframe were included, and, on retrospective analysis, were divided into
      two groups. Group A received RT with surgery, and Group B received surgery alone.
      The primary endpoint was local recurrence-free survival (LRFS). RESULTS: Overall,
      390 patients were included (318 in Group A and 72 in Group B), with a median
      follow-up of 53 months. The main reasons for avoiding RT were patient choice and
      technical considerations (vascular bypass or flap reconstruction). No difference
      in R0 resection was seen between the groups (79% vs. 70%; p = 0.18), but Group A
      had more G3 tumors (80.5% vs. 68%; p = 0.021). No difference in 5-year LRFS was
      evident (84% vs. 81%; p = 0.16). CONCLUSIONS: LRFS did not differ between
      patients with high-risk STSs receiving perioperative RT and those treated with
      surgery alone. The study was retrospective and omission of RT was largely
      uncontrolled with inherent bias. Nonetheless, data suggest that in experienced
      centers, the omission of RT did not diminish local disease outcome. Future
      studies on a selective approach to RT administration are awaited.

PMID- 29470820
TI  - The Impact of Intraoperative Re-Resection of a Positive Bile Duct Margin on
      Clinical Outcomes for Hilar Cholangiocarcinoma.
AB  - BACKGROUND: The impact of re-resection of a positive intraoperative bile duct
      margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA)
      remains controversial. We sought to define the impact of re-resection of an
      initially positive frozen-section bile duct margin on outcomes of patients
      undergoing surgery for HCCA. METHODS: Patients who underwent curative-intent
      resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary
      centers. Short- and long-term outcomes were analyzed among patients stratified by
      margin status. RESULTS: Among 215 (83.7%) patients who underwent frozen-section
      evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal
      margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary
      negative margin (secondary R0). There was no difference in morbidity, 30-day
      mortality, and length of stay among patients who had primary R0, secondary R0,
      and R1 resection (all p > 0.10). Median and 5-year survival were 22.3 months and
      23.3%, respectively, among patients who had a primary R0 resection compared with
      18.5 months and 7.9%, respectively, for patients with an R1 resection (p = 0.08).
      In contrast, among patients who had a secondary R0 margin with re-resection of
      the bile duct margin, median and 5-year survival were 30.6 months and 44.3%,
      respectively, which was comparable to patients with a primary R0 margin (p =
      0.804). On multivariable analysis, R1 margin resection was associated with
      decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0
      1.7; p = 0.027), but secondary R0 resection was associated with comparable long
      term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4-2.3; p = 0.829).
      CONCLUSIONS: Additional resection of a positive frozen-section ductal margin to
      achieve R0 resection was associated with improved long-term outcomes following
      curative-intent resection of HCCA.

PMID- 29470821
TI  - Is EQ-5D-5L Better Than EQ-5D-3L? A Head-to-Head Comparison of Descriptive
      Systems and Value Sets from Seven Countries.
AB  - OBJECTIVE: This study describes the first empirical head-to-head comparison of EQ
      5D-3L (3L) and EQ-5D-5L (5L) value sets for multiple countries. METHODS: A large
      multinational dataset, including 3L and 5L data for eight patient groups and a
      student cohort, was used to compare 3L versus 5L value sets for Canada, China,
      England/UK (5L/3L, respectively), Japan, The Netherlands, South Korea and Spain.
      We used distributional analyses and two methods exploring discriminatory power:
      relative efficiency as assessed by the F statistic, and an area under the curve
      for the receiver-operating characteristics approach. Differences in outcomes were
      explored by separating descriptive system effects from valuation effects, and by
      exploring distributional location effects. RESULTS: In terms of distributional
      evenness, efficiency of scale use and the face validity of the resulting
      distributions, 5L was superior, leading to an increase in sensitivity and
      precision in health status measurement. When compared with 5L, 3L systematically
      overestimated health problems and consequently underestimated utilities. This led
      to bias, i.e. over- or underestimations of discriminatory power. CONCLUSION: We
      conclude that 5L provides more precise measurement at individual and group
      levels, both in terms of descriptive system data and utilities. The increased
      sensitivity and precision of 5L is likely to be generalisable to longitudinal
      studies, such as in intervention designs. Hence, we recommend the use of the 5L
      across applications, including economic evaluation, clinical and public health
      studies. The evaluative framework proved to be useful in assessing preference
      based instruments and might be useful for future work in the development of
      descriptive systems or health classifications.

PMID- 29470822
TI  - The concept of the CCN protein family revisited: a centralized coordination
      network.
AB  - The wide array of biological properties attributed to the CCN family of proteins
      (Perbal in Lancet 363(9402):62-64, 2004) led me to reconsider the possible
      relationship and roles that these proteins may play as a team, instead of acting
      on their own as individual regulators in various signaling pathways. The dynamic
      model which I present in this review stems from the contribution of the
      biological properties that we established for CCN3, one of the three founding
      members of the CCN family, which was identified by our group as the first CCN
      protein showing growth inhibitory properties (1992), expressed mainly in
      quiescent cells (1996), and showing anti-tumor activities in several cellular
      models both ex vivo and in vivo. At the present time CCN3 is the only member of
      the family that has been reported to negatively act on the progression of the
      cell cycle. The unique dual localisation of CCN3 in the nucleus and outside
      cells, either at the membrane or in the extracellular matrix, that I first
      established in 1999, and that now appears to be shared by several other CCN
      proteins, is a unique essential feature which can no longer be ignored. Based on
      the structural and functional properties of CCN3, shared by most of the CCN
      family members, I propose an " all in one " concept in which CCN proteins are
      team members with specific functions that are aimed at the same goal. This model
      accounts both for the functional specificity of the various CCN proteins, their
      sequential and opposite or complementary effects in various biological context,
      and for the biological consequences of their physical interaction and biological
      cross-regulation.

PMID- 29470824
TI  - Turning Up the Heat: An Evaluation of the Evidence for Heating to Promote
      Exercise Recovery, Muscle Rehabilitation and Adaptation.
AB  - Historically, heat has been used in various clinical and sports rehabilitation
      settings to treat soft tissue injuries. More recently, interest has emerged in
      using heat to pre-condition muscle against injury. The aim of this narrative
      review was to collate information on different types of heat therapy, explain the
      physiological rationale for heat therapy, and to summarise and evaluate the
      effects of heat therapy before, during and after muscle injury, immobilisation
      and strength training. Studies on skeletal muscle cells demonstrate that heat
      attenuates cellular damage and protein degradation (following in vitro
      challenges/insults to the cells). Heat also increases the expression of heat
      shock proteins (HSPs) and upregulates the expression of genes involved in muscle
      growth and differentiation. In rats, applying heat before and after muscle injury
      or immobilisation typically reduces cellular damage and muscle atrophy, and
      promotes more rapid muscle growth/regeneration. In humans, some research has
      demonstrated benefits of microwave diathermy (and, to a lesser extent, hot water
      immersion) before exercise for restricting muscle soreness and restoring muscle
      function after exercise. By contrast, the benefits of applying heat to muscle
      after exercise are more variable. Animal studies reveal that applying heat during
      limb immobilisation attenuates muscle atrophy and oxidative stress. Heating
      muscle may also enhance the benefits of strength training for improving muscle
      mass in humans. Further research is needed to identify the most effective forms
      of heat therapy and to investigate the benefits of heat therapy for restricting
      muscle wasting in the elderly and those individuals recovering from serious
      injury or illness.

PMID- 29470825
TI  - Effect of Resistance Training Frequency on Gains in Muscular Strength: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Current recommendations on resistance training (RT) frequency for
      gains in muscular strength are based on extrapolations from limited evidence on
      the topic, and thus their practical applicability remains questionable.
      OBJECTIVE: To elucidate this issue, we conducted a systematic review and meta
      analysis of the studies that compared muscular strength outcomes with different
      RT frequencies. METHODS: To carry out this review, English-language literature
      searches of the PubMed/MEDLINE, Scopus, and SPORTDiscus databases were conducted.
      The meta-analysis was performed using a random-effects model. The meta-analysis
      models were generated with RT frequencies classified as a categorical variable as
      either 1, 2, 3, or 4+ times/week, or, if there were insufficient data in subgroup
      analyses, the training frequencies were categorized as 1, 2, or 3 times/week.
      Subgroup analyses were performed for potential moderators, including (1) training
      volume; (2) exercise selection for the 1 repetition maximum (RM) test (for both
      multi-joint and single-joint exercises); (3) upper and lower body strength gains;
      (4) training to muscular failure (for studies involving and not involving
      training to muscular failure); (5) age (for both middle-aged/older adults and
      young adults); and (6) sex (for men and for women). The methodological quality of
      studies was appraised using the modified Downs and Black checklist. RESULTS: A
      total of 22 studies were found to meet the inclusion criteria. The average score
      on the Downs and Black checklist was 18 (range 13-22 points). Four studies were
      classified as being of good methodological quality, while the rest were
      classified as being of moderate methodological quality. Results of the meta
      analysis showed a significant effect (p = 0.003) of RT frequency on muscular
      strength gains. Effect sizes increased in magnitude from 0.74, 0.82, 0.93, and
      1.08 for training 1, 2, 3, and 4+ times per week, respectively. A subgroup
      analysis of volume-equated studies showed no significant effect (p = 0.421) of RT
      frequency on muscular strength gains. The subgroup analysis for exercise
      selection for the 1RM test suggested a significant effect of RT frequency on
      multi-joint (p < 0.001), but not single-joint, 1RM test results (p = 0.324). The
      subgroup analysis for upper and lower body showed a significant effect of
      frequency (p = 0.004) for upper body, but not lower body, strength gains (p =
      0.070). In the subgroup analysis for studies in which the training was and was
      not carried out to muscular failure, no significant effect of RT frequency was
      found. The subgroup analysis for the age groups suggested a significant effect of
      training frequency among young adults (p = 0.024), but not among middle-aged and
      older adults (p = 0.093). Finally, the subgroup analysis for sex indicated a
      significant effect of RT frequency on strength gains in women (p = 0.030), but
      not men (p = 0.190). CONCLUSIONS: The results of the present systematic review
      and meta-analysis suggest a significant effect of RT frequency as higher training
      frequencies are translated into greater muscular strength gains. However, these
      effects seem to be primarily driven by training volume because when the volume is
      equated, there was no significant effect of RT frequency on muscular strength
      gains. Thus, from a practical standpoint, greater training frequencies can be
      used for additional RT volume, which is then likely to result in greater muscular
      strength gains. However, it remains unclear whether RT frequency on its own has
      significant effects on strength gain. It seems that higher RT frequencies result
      in greater gains in muscular strength on multi-joint exercises in the upper body
      and in women, and, finally, in contrast to older adults, young individuals seem
      to respond more positively to greater RT frequencies. More evidence among
      resistance-trained individuals is needed as most of the current studies were
      performed in untrained participants.

PMID- 29470826
TI  - Small papillary thyroid carcinoma with minimal extrathyroidal extension should be
      managed as ATA low-risk tumor.
AB  - PURPOSE: According to American Thyroid Association (ATA) guideline, papillary
      thyroid cancer (PTC) with minimal extrathyroidal extension (mETE) is classified
      at "intermediate risk" of persistent/recurrent disease. However, the impact of
      mETE per se on patients' outcome is not fully understood. The aim of our study
      was to evaluate the prognostic significance of mETE in patients with PTC not
      submitted to therapeutic or prophylactic lymph node dissection, according to
      tumor size and other prognostic factors. PATIENTS AND METHODS: We retrospectively
      evaluated a total of 514 PTC patients: 127 (24.7%) had mETE (pT3Nx) and 387
      (75.3%) had negative margins (pT1-2Nx). At a median follow-up of 9.1 years,
      patients were divided in two groups: patients with "good outcome" (no evidence of
      disease) and patients with "poor outcome" (persistent structural disease or
      recurrent disease or tumor-related death). RESULTS: The rate of patients with
      "poor outcome" was significantly higher in patients with mETE compared with
      patients with negative margins (11.8 versus 5.1%; OR 2.4576, 95% CI 1.2178
      4.9594, p = 0.01). However, mETE was significantly associated with poor outcome
      only in patients with tumors larger than 1.5 cm. CONCLUSIONS: mETE is an
      unfavorable prognostic factor in tumors larger than 1.5 cm, suggesting that, in
      the absence of other unfavorable characteristics, smaller tumors with mETE should
      be classified and managed as "low risk" tumors.

PMID- 29470827
TI  - In Vitro Characterization and Evaluation of the Cytotoxicity Effects of Nisin and
      Nisin-Loaded PLA-PEG-PLA Nanoparticles on Gastrointestinal (AGS and KYSE-30),
      Hepatic (HepG2) and Blood (K562) Cancer Cell Lines.
AB  - The aim of this study was an in vitro evaluation and comparison of the cytotoxic
      effects of free nisin and nisin-loaded PLA-PEG-PLA nanoparticles on
      gastrointestinal (AGS and KYSE-30), hepatic (HepG2), and blood (K562) cancer cell
      lines. To create this novel anti-cancer drug delivery system, the nanoparticles
      were synthesized and then loaded with nisin. Subsequently, their
      biocompatibility, ability to enter cells, and physicochemical properties,
      including formation, size, and shape, were studied using hemolysis, fluorescein
      isothiocyanate (FITC), Fourier transform infrared (FTIR) spectroscopy, dynamic
      light scattering (DLS), and scanning electron microscopy (SEM), respectively.
      Then, its loading efficiency and release kinetics were examined to assess the
      potential impact of this formulation for the nanoparticle carrier candidacy. The
      cytotoxicities of nisin and nisin-loaded nanoparticles were evaluated by using
      the MTT and Neutral Red (NR) uptake assays. Detections of the apoptotic cells
      were done via Ethidium Bromide (EB)/Acridine Orange (AO) staining. The FTIR
      spectra, SEM images, and DLS graph confirmed the formations of the nanoparticles
      and nisin-loaded nanoparticles with spherical, distinct, and smooth surfaces and
      average sizes of 100 and 200 nm, respectively. The loading efficiency of the
      latter nanoparticles was about 85-90%. The hemolysis test represented their non
      cytotoxicities and the FITC images indicated their entrance inside the cells. An
      increase in the percentage of apoptotic cells was observed through EB/AO
      staining. These results demonstrated that nisin had a cytotoxic effect on AGS,
      KYSE-30, HepG2, and K562 cancer cell lines, while the cytotoxicity of nisin
      loaded nanoparticles was more than that of the free nisin.

PMID- 29470828
TI  - Enhancement of Dissolution and Skin Permeability of Pentazocine by Proniosomes
      and Niosomal Gel.
AB  - Proniosomes (PN) are the dry water-soluble carrier systems that may enhance the
      oral bioavailability, stability, and topical permeability of therapeutic agents.
      The low solubility and low oral bioavailability due to extensive first pass
      metabolism make Pentazocine as an ideal candidate for oral and topical sustained
      release delivery. The present study was aimed to formulate the PNs by quick
      slurry method that are converted to niosomes (liquid dispersion) by hydration,
      and subsequently formulated to semisolid niosomal gel. The PNs were found in
      spherical shape in the SEM and stable in the physicochemical and thermal analysis
      (FTIR, TGA, and XRD). The quick slurry method produced high recovery (> 80%
      yield) and better flow properties (theta = 28.1-37.4 degrees ). After hydration,
      the niosomes exhibited desirable entrapment efficiency (44.45-76.23%), size (4.98
      21.3 MUm), and zeta potential (- 9.81 to - 21.53 mV). The in vitro drug release
      (T100%) was extended to more than three half-lives (2-4 h) and showed good fit to
      Fickian diffusion indicated by Korsmeyer-Peppas model (n = 0.136-0.365 and R2 =
      0.9747-0.9954). The permeation of niosomal gel was significantly enhanced across
      rabbit skin compared to the pure drug-derived gel. Therefore, the PNs are found
      promising candidates for oral as dissolution enhancement and sustained release
      for oral and topical delivery of pentazocine for the management of cancer pain.

PMID- 29470829
TI  - Enhancing the Therapeutic Efficacy of Tamoxifen Citrate Loaded Span-Based Nano
      Vesicles on Human Breast Adenocarcinoma Cells.
AB  - Serious adverse effects and low selectivity to cancer cells are the main
      obstacles of long term therapy with Tamoxifen (Tmx). This study aimed to develop
      Tmx-loaded span-based nano-vesicles for delivery to malignant tissues with
      maximum efficacy. The effect of three variables on vesicle size (Y1), zeta
      potential (Y2), entrapment efficiency (Y3) and the cumulative percent release
      after 24 h (Y4) were optimized using Box-Behnken design. The optimized formula
      was prepared and tested for its stability in different storage conditions. The
      observed values for the optimized formula were 310.2 nm, - 42.09 mV, 75.45 and
      71.70% for Y1, Y2, Y3, and Y4, respectively. The examination using electron
      microscopy confirmed the formation of rounded vesicles with distinctive bilayer
      structure. Moreover, the cytotoxic activity of the optimized formula on both
      breast cancer cells (MCF-7) and normal cells (BHK) showed enhanced selectivity
      (9.4 folds) on cancerous cells with IC50 values 4.7 +/- 1.5 and 44.3 +/- 1.3
      MUg/ml on cancer and normal cells, respectively. While, free Tmx exhibited lower
      selectivity (2.5 folds) than optimized nano-vesicles on cancer cells with IC50
      values of 9.0 +/- 1.1 MUg/ml and 22.5 +/- 5.3 MUg/ml on MCF-7 and BHK cells,
      respectively. The promising prepared vesicular system, with greater efficacy and
      selectivity, provides a marvelous tool to overcome breast cancer treatment
      challenges.

PMID- 29470823
TI  - Methodological Characteristics and Future Directions for Plyometric Jump Training
      Research: A Scoping Review.
AB  - Recently, there has been a proliferation of published articles on the effect of
      plyometric jump training, including several review articles and meta-analyses.
      However, these types of research articles are generally of narrow scope.
      Furthermore, methodological limitations among studies (e.g., a lack of
      active/passive control groups) prevent the generalization of results, and these
      factors need to be addressed by researchers. On that basis, the aims of this
      scoping review were to (1) characterize the main elements of plyometric jump
      training studies (e.g., training protocols) and (2) provide future directions for
      research. From 648 potentially relevant articles, 242 were eligible for inclusion
      in this review. The main issues identified related to an insufficient number of
      studies conducted in females, youths, and individual sports (~ 24.0, ~ 37.0, and
      ~ 12.0% of overall studies, respectively); insufficient reporting of effect size
      values and training prescription (~ 34.0 and ~ 55.0% of overall studies,
      respectively); and studies missing an active/passive control group and
      randomization (~ 40.0 and ~ 20.0% of overall studies, respectively). Furthermore,
      plyometric jump training was often combined with other training methods and added
      to participants' daily training routines (~ 47.0 and ~ 39.0% of overall studies,
      respectively), thus distorting conclusions on its independent effects.
      Additionally, most studies lasted no longer than 7 weeks. In future, researchers
      are advised to conduct plyometric training studies of high methodological quality
      (e.g., randomized controlled trials). More research is needed in females, youth,
      and individual sports. Finally, the identification of specific dose-response
      relationships following plyometric training is needed to specifically tailor
      intervention programs, particularly in the long term.

PMID- 29470830
TI  - Strong enhancement by IGF1-R antagonists of hepatocellular carcinoma cell
      migration inhibition by Sorafenib and/or vitamin K1.
AB  - PURPOSE: Emerging evidence indicates that combining Sorafenib with vitamin K1
      (VK1) may result in a synergistic inhibition of hepatocellular carcinoma (HCC)
      cell migration and proliferation. Despite this synergy, its benefits may be
      limited due to drug resistance resulting from cross-talk with the tumor
      microenvironment. Insulin-like growth factor-1 (IGF1) signaling acts as an
      important modulator of HCC cell growth, motility and drug resistance. Therefore,
      we aimed to explore the effects of Sorafenib in combination with VK1 and/or IGF1
      R antagonists on HCC cells. METHODS: Scratch wound migration assays were
      performed to assess the motility of HCC-derived PLC/PRF/5, HLF and Hep3B cells.
      The synergistic, additive or antagonistic effects of Sorafenib, VK1 and IGF1-R
      antagonists on HCC cell motility were assessed using CompuSyn software. The
      effects mediated by these various compounds on HCC cytoskeleton organization were
      evaluated using DyLight 554 Phalloidin staining. Proliferation and migration
      associated signaling pathways were analyzed in PLC/PRF/5 cells using Erk1/2 and
      Akt activation kits and Western blotting (Mek, JNK, Akt, Paxillin and p38),
      respectively. RESULTS: The effects of the IGF1-R antagonists GSK1838705A and OSI
      906 on HCC cell migration inhibition after Sorafenib and/or VK1 administration,
      individually or in combination, were evaluated. We found a synergistic effect in
      PLC/PRF/5, HLF and Hep3B cells for combinations of fixed doses of GSK1838705A or
      OSI-906 together with different doses of Sorafenib and/or VK1. The levels of
      synergy were found to be stronger at higher Sorafenib and/or VK1 concentrations
      and lower or absent at lower concentrations, with some variation among the
      different cell lines tested. In addition, we found that in PLC/PRF/5 and HLF
      cells IGF1-R blockage strongly enhanced the reduction and redistribution of F
      actin induced by Sorafenib and/or VK1 through alterations in the phosphorylation
      levels of some of the principal proteins involved in the MAPK signaling cascade,
      which is essential for cell migration. CONCLUSIONS: Our results indicate that
      modulation of the efficacy of Sorafenib through combinations with VK1 and/or IGF1
      R antagonists results in synergistic inhibition of HCC cell migration.

PMID- 29470832
TI  - Real-World Treatment Patterns for Golimumab and Concomitant Medications in
      Japanese Rheumatoid Arthritis Patients.
AB  - INTRODUCTION: The aim of this study was to investigate real-world treatment
      patterns for use of golimumab and concomitant medications in Japanese patients
      with rheumatoid arthritis. METHODS: This study was a post hoc retrospective
      analysis from post-marketing surveillance data on 2350 Japanese patients with
      moderate/severe rheumatoid arthritis who received golimumab for 24 weeks. The
      study population was divided based on initiation treatment or dose adjustment
      patterns with golimumab, methotrexate, or oral glucocorticoids. RESULTS: Logistic
      regression analysis revealed that the baseline factors associated with
      administration of golimumab (100 mg) were higher body weight, failure of prior
      biological therapy (bio-failure), no previous methotrexate use, and respiratory
      disease, while previous methotrexate use and absence of renal impairment or
      respiratory disease were associated with concomitant methotrexate therapy, and
      previous glucocorticoid use was associated with concomitant glucocorticoid
      therapy. The following associations were identified with regard to dose
      adjustment during treatment: bio-failure, no previous methotrexate use, previous
      csDMARDs use, presence of respiratory disease, allergy history, and higher CRP
      for golimumab dose escalation; shorter disease duration, previous GC, and no
      previous methotrexate use for methotrexate dose escalation; no prior biological
      therapy and renal impairment for methotrexate dose reduction; no previous GC use
      for glucocorticoid dose escalation; and absence of Steinbrocker's stage
      II/III/IV, absence of Steinbrocker's class II, no bio-failure, and no previous
      csDMARDs use for glucocorticoid dose reduction. CONCLUSIONS: This study revealed
      that various baseline factors were associated with initiation of treatment and
      dose adjustment of golimumab, methotrexate, or oral glucocorticoids, reflecting
      both the treatment strategies of physicians for improving RA symptoms and/or
      reducing adverse events. FUNDING: Janssen Pharmaceutical K.K. and Mitsubishi
      Tanabe Pharma Corporation.

PMID- 29470831
TI  - Expression and function of immune ligand-receptor pairs in NK cells and cancer
      stem cells: therapeutic implications.
AB  - BACKGROUND: The interplay between the immune system and cancer cells has come to
      the forefront of cancer therapeutics, with novel immune blockade inhibitors being
      approved for the treatment of an increasing list of cancers. However, the
      majority of cancer patients still display or develop resistance to these
      promising drugs. It is possible that cancer stem cells (CSCs) are contributing to
      this therapeutic resistance. Although CSCs usually represent a small percentage
      of the total number of cancer cells, they are endowed with the ability of self
      renewal and to produce differentiated progeny. Additionally, they have shown the
      capacity to establish tumors after transplantation to animals, even in small
      numbers. CSCs have also been found to be resistant to various anti-cancer
      therapies, including chemotherapy, radiation therapy and, more recently,
      immunotherapy. This is true despite the sensitivity of CSCs to lysis in vitro by
      natural killer (NK) cells, the main effector cells of the innate immune system.
      In this paper the expression of ligands specific for NK cells on CSCs, the
      intracellular network responsible for the expression of the NK cytotoxicity
      receptors, and the status of activation of NK cells in the tumor micro
      environment are reviewed. The aim of this review is to highlight potential
      strategies for overcoming CSC immune resistance, thereby enhancing the efficacy
      of current and future anti-cancer therapies. THERAPEUTIC IMPLICATIONS: NK cell
      activation in the tumor micro-environment through drugs neutralizing inhibitory
      immune receptors, and combined with other drugs harnessing the potential of the
      adaptive immune system, could be the most effective approach for attacking both
      stem cell and non-stem cell cancer populations.

PMID- 29470833
TI  - Cost of Depression in Japanese Patients with Rheumatoid Arthritis: Evidence from
      Administrative Data.
AB  - INTRODUCTION: To determine the cost of depression comorbidity among Japanese
      adults with rheumatoid arthritis (RA). METHODS: A retrospective database study of
      8968 patients diagnosed with RA between 2010 and 2015 and treated with any RA
      medication was conducted. Health care utilization characteristics were compared
      between patients with and without a comorbidity of depression. Propensity score
      matching was applied to ensure a balanced comparison between the two cohorts.
      RESULTS: The prevalence of a depression comorbidity was found for 5% of the total
      RA patients. This comorbidity was associated with 62% (56%) higher total
      outpatient visits and 66% (163%) higher rate of emergency room visits after 6
      (12) months. CONCLUSIONS: Burden of depression among RA patients in Japan is
      relatively high and awareness for depression as a comorbidity of RA needs to be
      reinforced. FUNDING: Janssen Pharmaceutical KK.

PMID- 29470834
TI  - Worldwide, 3-Year, Post-Marketing Surveillance Experience with Tofacitinib in
      Rheumatoid Arthritis.
AB  - INTRODUCTION: Post-marketing surveillance (PMS) is an integral part of monitoring
      adverse events (AEs) following approval of new drugs. Tofacitinib is an oral
      Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). An
      analysis of PMS reports was conducted to evaluate the safety of tofacitinib in a
      post-marketing setting. METHODS: Worldwide tofacitinib PMS data received in the
      Pfizer safety database from November 6, 2012 (first marketing authorization of
      tofacitinib) to November 5, 2015 were analyzed. Serious AEs (SAEs) of interest
      were reviewed and reporting rates (RRs) were calculated by dividing the number of
      SAEs by the estimated 100 patient-years of exposure. Patient exposure was
      calculated based on estimated worldwide sales and an estimated daily regimen of
      tofacitinib 5 mg twice daily. RESULTS: During the 3-year reporting period,
      worldwide post-marketing exposure to tofacitinib since approval was estimated to
      be 34,223 patient-years. In total, 9291 case reports (82.9% non-serious) were
      received and 25,417 AEs, 102 fatal cases, and 4352 SAEs were reported. The RRs
      (per 100 patient-years) for SAEs of interest by Medical Dictionary for Regulatory
      Activities System Organ Class were 2.57 for infections, 0.91 for gastrointestinal
      disorders, 0.60 for respiratory disorders, 0.45 for neoplasms, 0.43 for cardiac
      disorders, and 0.12 for hepatobiliary disorders. CONCLUSIONS: Although there are
      limitations to these data, no new safety risks were revealed in this real-world
      setting compared with the safety profile identified in the tofacitinib RA
      clinical development program. Any risks identified through the tofacitinib
      development program and PMS will continue to be monitored through
      pharmacovigilance surveillance. FUNDING: Pfizer Inc.

PMID- 29470835
TI  - Costs of Disease Relapses Among Individuals with Granulomatosis, with
      Polyangiitis, or Microscopic Polyangiitis in the United States.
AB  - INTRODUCTION: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis
      (MPA) are two related forms of systemic vasculitis. Patients with these
      conditions often experience relapses affecting various body systems. Here we
      describe rates of relapse and review healthcare costs resulting from relapse
      among patients with GPA/MPA. METHODS: Two groups of patients with GPA and MPA
      were selected from the MarketScan claims databases between 2011 and 2013 based on
      diagnosis codes. Patients were followed for 12 months to identify relapses based
      on an algorithm of diagnoses in medical and medication claims. Relapses were
      categorized into one of the following groups: renal relapse, pulmonary relapse,
      other relapse-associated condition relapse, GPA or MPA utilization relapse, and
      mixed relapse. RESULTS: The final sample of patients with GPA and MPA consisted
      of 2707 and 740 patients, respectively. In both groups, approximately one-quarter
      of patients experienced relapse during the 12-month follow-up period. The mean
      all-cause healthcare costs in the 4-month period after relapse were $38,313 (SD,
      $54,120) for patients with GPA and $35,947 (SD, $48,065) for patients with MPA.
      In both groups, renal relapses were the costliest. Costs during the 4 months
      immediately following relapses were substantially higher than what could be
      expected over a 4-month follow-up among patients who did not experience relapse
      based on 12-month all-cause costs (GPA, $32,005 [SD, $64,570]; MPA, $61,044 [SD,
      $125,093]). CONCLUSIONS: Relapses are common among patients with GPA and MPA, and
      treatment of relapses can be costly. More effective therapies are needed to
      prevent relapses. FUNDING: Genentech, Inc.

PMID- 29470836
TI  - Role of Vancomycin Minimum Inhibitory Concentrations by Modified Population
      Analysis Profile Method and Clinical Outcomes in High Inoculum Methicillin
      Resistant Staphylococcus aureus Infections.
AB  - INTRODUCTION: Vancomycin remains the standard of care for invasive methicillin
      resistant Staphylococcus aureus (MRSA) infections. Treatment failures from
      heteroresistant vancomycin-intermediate subpopulations (hVISA) are challenging to
      detect. Minimum inhibitory concentrations (MIC) identified by modified population
      analysis profile (PAP) is an alternative testing method. The aim of this study
      was to evaluate the role of PAP MIC on vancomycin failures in two high inoculum
      infections: MRSA infective endocarditis and pneumonia. METHODS: Retrospective,
      observational study at Detroit Medical Center from 2008 to 2016. Adults >= 18
      years with >= 1 positive MRSA blood culture from IE or pneumonia source and
      received >= 48 h vancomycin were included. The primary outcome was composite
      failure: MRSA bacteremia >= 7 days or 30-day all-cause mortality. RESULTS: A
      total of 191 patients were included; 47.6% IE and 52.4% pneumonia. About 19% were
      hVISA isolates, median vancomycin PAP MIC of 3 (2, 3). More than half (54.5%)
      experienced composite failure with a larger proportion of PAP MIC >= 4 mg/L in
      this group (25 vs. 15%, p = 0.086). Patients with IE experienced prolonged
      bacteremia whereas patients with pneumonia experienced higher 30-day mortality.
      On logistic regression analysis, age [adjusted odds ratio (aOR), 1.026; 95%
      confidence interval (CI), 1.005-1.047; p = 0.014] and APACHE II score (aOR 1.039;
      95% CI, 1.004-1.076; p = 0.029) independently predicted composite failure.
      CONCLUSION: Vancomycin PAP MIC may be a more relevant predictor of patient
      outcomes in persistent bacteremic MRSA infections (e.g., IE). This susceptibility
      method is less applicable in other high inoculum infections with shorter
      bacteremia durations and higher mortality rates (e.g., pneumonia).

PMID- 29470837
TI  - Past, Present and Future Approaches to the Prevention and Treatment of
      Respiratory Syncytial Virus Infection in Children.
AB  - INTRODUCTION: The REGAL (RSV Evidence - A Geographical Archive of the Literature)
      series has provided a comprehensive review of the published evidence in the field
      of respiratory syncytial virus (RSV) in Western countries over the last 20 years.
      This seventh and final publication covers the past, present and future approaches
      to the prevention and treatment of RSV infection among infants and children.
      METHODS: A systematic review was undertaken of publications between January 1,
      1995 and December 31, 2017 across PubMed, Embase and The Cochrane Library.
      Studies reporting data on the effectiveness and tolerability of prophylactic and
      therapeutic agents for RSV infection were included. Study quality and strength of
      evidence (SOE) were graded using recognized criteria. A further nonsystematic
      search of the published literature and Clinicaltrials.gov on antiviral therapies
      and RSV vaccines currently in development was also undertaken. RESULTS: The
      systematic review identified 1441 studies of which 161 were included. Management
      of RSV remains centered around prophylaxis with the monoclonal antibody
      palivizumab, which has proven effective in reducing RSV hospitalization (RSVH) in
      preterm infants < 36 weeks' gestational age (72% reduction), children with
      bronchopulmonary dysplasia (65% reduction), and infants with hemodynamically
      significant congenital heart disease (53% reduction) (high SOE). Palivizumab has
      also shown to be effective in reducing recurrent wheezing following RSVH (high
      SOE). Treatment of RSV with ribavirin has conflicting success (moderate SOE).
      Antibodies with increased potency and extended half-life are currently entering
      phase 3 trials. There are approximately 15 RSV vaccines in clinical development
      targeting the infant directly or indirectly via the mother. CONCLUSION:
      Palivizumab remains the only product licensed for RSV prophylaxis, and only
      available for high-risk infants. For the general population, there are several
      promising vaccines and monoclonal antibodies in various stages of clinical
      development, with the aim to significantly reduce the global healthcare impact of
      this common viral infection. FUNDING: AbbVie.

PMID- 29470838
TI  - First-Line Cetuximab Monotherapy in KRAS/NRAS/BRAF Mutation-Negative Colorectal
      Cancer Patients.
AB  - BACKGROUND: Colorectal carcinomas (CRCs) are sensitive to treatment by anti
      epidermal growth factor receptor (EGFR) antibodies only if they do not carry
      activating mutations in down-stream EGFR targets (KRAS/NRAS/BRAF). Most clinical
      trials for chemo-naive CRC patients involved combination of targeted agents and
      chemotherapy, while single-agent cetuximab or panitumumab studies included either
      heavily pretreated patients or subjects who were not selected on the basis of
      molecular tests. We hypothesized that anti-EGFR therapy would have significant
      efficacy in chemo-naive patients with KRAS/NRAS/BRAF mutation-negative CRC.
      METHODS: Nineteen patients were prospectively included in the study. RESULTS: Two
      (11%) patients experienced partial response (PR) and 11 (58%) subjects showed
      stable disease (SD). Median time to progression approached 6.1 months (range 1.6
      15.0 months). Cetuximab efficacy did not correlate with RNA expression of EGFR
      and insulin-like growth factor 2 (IGF2). Only one tumor carried PIK3CA mutation,
      and this CRC responded to cetuximab. Exome analysis of patients with progressive
      disease (PD) revealed 1 CRC with high-level microsatellite instability and 1
      instance of HER2 oncogene amplification; 3 of 4 remaining patients with PD had
      allergic reactions to cetuximab, while none of the subjects with PR or SD had
      this complication. Comparison with 19 retrospective KRAS/NRAS/BRAF mutation
      negative patients receiving first-line fluoropyrimidines revealed no advantages
      or disadvantages of cetuximab therapy. CONCLUSIONS: Cetuximab demonstrates only
      modest efficacy when given as a first-line monotherapy to KRAS/NRAS/BRAF mutation
      negative CRC patients. It is of question, why meticulous patient selection, which
      was undertaken in the current study, did not result in the improvement of
      outcomes of single-agent cetuximab treatment.

PMID- 29470840
TI  - Thermal Transition of Bimetallic Metal-Phenolic Networks to Biomass-Derived
      Hierarchically Porous Nanofibers.
AB  - The development and utilization of biomass resources could contribute to new
      materials for long-term sustainable energy storage and environmental
      applications, reduce environmental impacts, and meet the urgent need for green
      and sustainable development strategies. Herein, a bimetallic metal-phenolic
      network (MPN) was applied to incorporate different metallic element species into
      cattle skin and fabricate collagen-fiber-derived complex oxide nanofibers using
      natural polyphenols (Myrica tannins). Direct thermal transition of these biomass
      MPN composites generates hierarchically porous nanofibers possessing micro- and
      mesoporous architectures along with a well-preserved macroscopic structure. The
      pore system and complex oxide composition provide excellent photocatalytic
      performance. This low-cost, simple, and readily scalable MPN-based approach
      provides a straightforward route to synthesize nanostructured materials directly
      from biomass, which could play important roles in a wide range of potential
      applications.

PMID- 29470839
TI  - Embryonic neurogenesis in echinoderms.
AB  - The phylogenetic position of echinoderms is well suited to revealing shared
      features of deuterostomes that distinguish them from other bilaterians. Although
      echinoderm neurobiology remains understudied, genomic resources, molecular
      methods, and systems approaches have enabled progress in understanding mechanisms
      of embryonic neurogenesis. Even though the morphology of echinoderm larvae is
      diverse, larval nervous systems, which arise during gastrulation, have numerous
      similarities in their organization. Diverse neural subtypes and specialized
      sensory neurons have been identified and details of neuroanatomy using neuron
      specific labels provide hypotheses for neural function. The early patterning of
      ectoderm and specification of axes has been well studied in several species and
      underlying gene regulatory networks have been established. The cells giving rise
      to central and peripheral neural components have been identified in urchins and
      sea stars. Neurogenesis includes typical metazoan features of asymmetric division
      of neural progenitors and in some cases limited proliferation of neural
      precursors. Delta/Notch signaling has been identified as having critical roles in
      regulating neural patterning and differentiation. Several transcription factors
      functioning in pro-neural phases of specification, neural differentiation, and
      sub-type specification have been identified and structural or functional
      components of neurons are used as differentiation markers. Several methods for
      altering expression in embryos have revealed aspects of a regulatory hierarchy of
      transcription factors in neurogenesis. Interfacing neurogenic gene regulatory
      networks to the networks regulating ectodermal domains and identifying the
      spatial and temporal inputs that pattern the larval nervous system is a major
      challenge that will contribute substantially to our understanding of the
      evolution of metazoan nervous systems. This article is categorized under:
      Comparative Development and Evolution > Model Systems Comparative Development and
      Evolution > Body Plan Evolution Early Embryonic Development > Gastrulation and
      Neurulation.

PMID- 29470841
TI  - Disease Duration and Stage Influence Bone Microstructure in Patients With Primary
      Biliary Cholangitis.
AB  - Primary biliary cholangitis (PBC) is known to be a major risk factor for
      osteoporosis reflected by a reduction of bone mineral density (BMD). However,
      both the extent of the macro- and microstructural alterations of bone as well as
      the causative factors are unknown. We have retrospectively analyzed a total of 96
      patients with PBC and 53 healthy controls matched for age, sex, and body mass
      index. In addition to dual-energy X-ray absorptiometry (DXA) measurements at the
      lumbar spine and hip, high-resolution peripheral quantitative computed tomography
      (HR-pQCT) was used to assess the geometric, volumetric, and microstructural
      changes of bone at the distal radius and tibia. Furthermore, serum analyses and
      measures of disease duration and stage including transient elastography were
      performed. Total, cortical, and trabecular volumetric BMD as well as geometric
      parameters were significantly reduced in PBC patients. Microstructural analysis
      revealed a significantly lower cortical thickness (p < 0.001) and bone volume per
      tissue volume (p < 0.001) in the radius and tibia but unchanged trabecular number
      in patients with PBC (radius: p = 0.42; tibia: p = 0.12). Multivariate regression
      models pointed out that disease duration and stage are the primary factors that
      are independently associated with bone loss in PBC. A subgroup analysis of
      patients with additional autoimmune hepatitis (AIH) revealed no significant
      changes in bone structure compared with PBC only. Taken together, PBC patients
      demonstrate severe alterations in bone microstructure that are positively
      associated with disease duration and stage. By applying HR-pQCT in the distal
      radius and tibia, a combined bone loss syndrome expressed by a predominant
      decrease in BMD and cortical thickness could be detected. (c) 2018 American
      Society for Bone and Mineral Research.

PMID- 29470842
TI  - Elucidating the Nature of the Excited State of a Heteroleptic Copper
      Photosensitizer by using Time-Resolved X-ray Absorption Spectroscopy.
AB  - We report the light-induced electronic and geometric changes taking place within
      a heteroleptic CuI photosensitizer, namely [(xant)Cu(Me2 phenPh2 )]PF6
      (xant=xantphos, Me2 phenPh2 =bathocuproine), by time-resolved X-ray absorption
      spectroscopy in the ps-MUs time regime. Time-resolved X-ray absorption near edge
      structure (XANES) and extended X-ray absorption fine structure (EXAFS) analysis
      enabled the elucidation of the electronic and structural configuration of the
      copper center in the excited state as well as its decay dynamics in different
      solvent conditions with and without triethylamine acting as a sacrificial
      electron donor. A three-fold decrease in the decay lifetime of the excited state
      is observed in the presence of triethylamine, showing the feasibility of the
      reductive quenching pathway in the latter case. A prominent pre-edge feature is
      observed in the XANES spectrum of the excited state upon metal to charge ligand
      transfer transition, showing an increased hybridization of the 3d states with the
      ligand p orbitals in the tetrahedron around the Cu center. EXAFS and density
      functional theory illustrate a significant shortening of the Cu-N and an
      elongation of the Cu-P bonds together with a decrease in the torsional angle
      between the xantphos and bathocuproine ligand. This study provides mechanistic
      time-resolved understanding for the development of improved heteroleptic CuI
      photosensitizers, which can be used for the light-driven production of hydrogen
      from water.

PMID- 29470843
TI  - A Polycarboxyl-Decorated FeIII -Based Xerogel-Derived Multifunctional Composite
      (Fe3 O4 /Fe/C) as an Efficient Electrode Material towards Oxygen Reduction
      Reaction and Supercapacitor Application.
AB  - Low cost, non-noble metal catalysts with a good oxygen reduction reaction (ORR)
      activity comparable to that of platinum and also having good energy storage
      properties are highly desirable but challenging. Several challenges are
      associated with the development of such materials. Herein, we demonstrate a new
      polycarboxyl-functionalised FeIII -based gel material, synthesised following a
      solvothermal method and the development of its composite (Fe3 O4 /Fe/C) by
      annealing at optimised temperature. The developed composite displayed excellent
      electrocatalytic activity for the oxygen reduction reaction with an onset
      potential of 0.87 V (vs. RHE) and a current density value of -5 mA cm-2 , which
      are comparable with commercial 20 wt % Pt/C. In addition, as one of the most
      desirable properties, the composite exhibits a better methanol tolerance and
      greater durability than Pt/C. The same material was explored as an energy storage
      material for supercapacitors, which showed a specific capacitance of 245 F g-1 at
      a current density of 1 A g-1 . It is expected that this Fe3 O4 /Fe/C composite
      with a disordered graphitised carbon matrix will pave a horizon for developing
      energy conversion and energy storage devices.

PMID- 29470844
TI  - Reference values for respiratory impedance measured by the forced oscillation
      technique in adult men and women.
AB  - INTRODUCTION: The forced oscillation technique (FOT) is a particularly useful
      test of the mechanical properties of the respiratory system that has an
      increasingly important role in lung function laboratories. There is general
      agreement in the literature that the determination of reference values is of
      utmost importance in the clinical use of the FOT. OBJECTIVE: Our aim was to
      present reference values for whole-breath FOT measurements, establish which
      anthropometric variables were more predictive of impedance parameters, and
      provide all the details to adequately adopt these reference equations in
      individual laboratories. METHODS: We prospectively evaluated a randomly selected
      non-smoking sample of the adult Brazilian population (288 subjects, 144 males and
      144 females aged 20-86 years). The volunteers were separated by sex and divided
      into six groups based on decade of age. Sex-specific linear prediction equations
      were developed by multiple regression analysis using age, body mass and height as
      explanatory variables. RESULTS: Age introduced a slight, but significant,
      reduction of resistance in men (P < .001) and women (P < .001). In general,
      significantly higher values of resistance were observed in females (P < .0001).
      Among the anthropometric variables analyzed, height was the best predictor for
      all parameters studied. CONCLUSION: This study provides an original frame of
      reference for the FOT in Brazilian males and females aged 20-86 years. Height was
      the best predictor of respiratory impedance parameters. Details contributing to
      an adequate adoption of these reference equations elsewhere by transference and
      verification are also provided.

PMID- 29470845
TI  - Electron cryotomography of Mycoplasma pneumoniae mutants correlates terminal
      organelle architectural features and function.
AB  - The Mycoplasma pneumoniae terminal organelle functions in adherence and gliding
      motility and is comprised of at least eleven substructures. We used electron
      cryotomography to correlate impaired gliding and adherence function with changes
      in architecture in diverse terminal organelle mutants. All eleven substructures
      were accounted for in the prkC, prpC and P200 mutants, and variably so for the
      HMW3 mutant. Conversely, no terminal organelle substructures were evident in HMW1
      and HMW2 mutants. The P41 mutant exhibits a terminal organelle detachment
      phenotype and lacked the bowl element normally present at the terminal organelle
      base. Complementation restored this substructure, establishing P41 as either a
      component of the bowl element or required for its assembly or stability, and that
      this bowl element is essential to anchor the terminal organelle but not for
      leverage in gliding. Mutants II-3, III-4 and topJ exhibited a visibly lower
      density of protein knobs on the terminal organelle surface. Mutants II-3 and III
      4 lack accessory proteins required for a functional adhesin complex, while the
      topJ mutant lacks a DnaJ-like co-chaperone essential for its assembly. Taken
      together, these observations expand our understanding of the roles of certain
      terminal organelle proteins in the architecture and function of this complex
      structure.

PMID- 29470846
TI  - Benchmarking the "Question, Persuade, Refer" Program Against Evaluations of
      Established Suicide Prevention Gatekeeper Trainings.
AB  - Gatekeeper training is a common approach for aiding suicidal youth. This study
      utilizes comparative effectiveness "benchmarks" from established programs to
      evaluate the Question, Persuade, Refer (QPR) program. The QPR program was
      implemented with adults (N = 2,389) working in youth-serving community agencies.
      Questionnaires assessed suicide prevention knowledge, attitudes, subjective
      norms, perceived behavioral control, and behaviors. Consistent with benchmarked
      studies, participants in QPR demonstrated knowledge and suicide prevention
      behavior gains compared with control groups. Future research should utilize
      benchmarking methods as a measure of effectiveness, and more thoroughly assess
      mechanisms that promote behavior change.

PMID- 29470847
TI  - Cryo-electron tomography analyses of terminal organelle mutants suggest the
      motility mechanism of Mycoplasma genitalium.
AB  - The terminal organelle of Mycoplasma genitalium is responsible for bacterial
      adhesion, motility and pathogenicity. Localized at the cell tip, it comprises an
      electron-dense core that is anchored to the cell membrane at its distal end and
      to the cytoplasm at its proximal end. The surface of the terminal organelle is
      also covered with adhesion proteins. We performed cellular cryoelectron
      tomography on deletion mutants of eleven proteins that are implicated in building
      the terminal organelle, to systematically analyze the ultrastructural effects.
      These data were correlated with microcinematographies, from which the motility
      patterns can be quantitatively assessed. We visualized diverse phenotypes,
      ranging from mild to severe cell adhesion, motility and segregation defects.
      Based on our observations, we propose a double-spring ratchet model for the
      motility mechanism that explains our current and previous observations. Our
      model, which expands and integrates the previously suggested inchworm model,
      allocates specific functions to each of the essential components of this unique
      bacterial motility system.

PMID- 29470848
TI  - Simultaneous determination of evodiamine and its four metabolites in rat plasma
      by LC-MS/MS and its application to a pharmacokinetic study.
AB  - A simple and sensitive liquid chromatography tandem mass spectrometry method was
      validated for simultaneous quantification of evodiamine and its metabolites 10
      hydroxyevodiamine (M1), 18-hydroxyevodiamine (M2), 10-hydroxyevodiamine
      glucuronide (M3) and 18-hydroxy- evodiamine-glucuronide (M4) in rat plasma for
      the first time. The analytes were extracted with acetonitrile and separated on a
      C18 column within 3 min. The detection was achieved in positive selected reaction
      monitoring mode with precursor-to-product transitions at m/z 304.1 -> 161.1 for
      evodiamine, m/z 320.1 -> 134.1 for M1, m/z 320.1 -> 150.1 for M2, m/z 496.2 ->
      134.1 for M3, m/z 496.2 -> 171.1 for M4 and m/z 349.2 -> 305.1 for camptothecin
      (internal standard). The linearity was evident over the tested concentration
      ranges with correlation coefficients >0.9991. The lower limits of quantification
      for evodiamine, M1, M2, M3 and M4 were 0.1, 0.1, 0.1, 0.25 and 0.25 ng mL-1 ,
      respectively. Extraction recoveries and matrix effects of the analytes were
      within the ranges of 84.51-97.21 and 90.13-103.30%, respectively. The accuracy
      (relative error) ranged from -8.14 to 7.23% while the intra- and inter-day
      precisions (relative standard deviation) were < 9.31%. The validated assay was
      successfully applied for the pharmacokinetic study of evodiamine, M1, M2, M3 and
      M4 in rat. The current study will be helpful in understanding the in vivo
      disposition of evodiamine.

PMID- 29470849
TI  - Direct Integration of Red-NIR Emissive Ceramic-like An M6 Xi8 Xa6 Metal Cluster
      Salts in Organic Copolymers Using Supramolecular Interactions.
AB  - Hybrid nanomaterials made of inorganic nanocomponents dispersed in an organic
      host raise an increasing interest as low-cost solution-processable functional
      materials. However, preventing phase segregation while allowing a high inorganic
      doping content remains a major challenge, and usual methods require a
      functionalization step prior integration. Herein, we report a new approach to
      design such nanocomposite in which ceramic-like metallic nanocluster compounds
      are embedded at 10 wt % in organic copolymers, without any functionalization.
      Dispersion homogeneity and stability are ensured by weak interactions occurring
      between the copolymer lateral chains and the nanocluster compound. Hybrids could
      be ink-jet printed and casted on a blue LED. This proof-of-concept device emits
      in the red-NIR area and generates singlet oxygen, O2 (1 Deltag), of particular
      interest for lights, display, sensors or photodynamic based therapy applications.

PMID- 29470850
TI  - Identification and functional analysis of a novel G310D variant in the insulin
      like growth factor 1 receptor (IGF1R) gene associated with type 2 diabetes in
      American Indians.
AB  - AIMS: Insulin-like growth factor 1 receptor (IGF1R) is involved in cell growth
      and glucose homeostasis. In the current study, the IGF1R locus was analysed as a
      candidate gene for type 2 diabetes (T2D) in American Indians. MATERIALS AND
      METHODS: Whole genome sequence data from 335 American Indians identified 3 novel
      missense variants in IGF1R. The associations of IGF1R variants with T2D, age of
      T2D onset and birth weight were analysed in a population-based sample of 7701
      American Indians. RESULTS: A novel glycine-to-aspartic acid substitution (G310D)
      in IGF1R was identified, which associated with T2D in a sex-specific manner (Psex
      interaction = 0.02). In women, the aspartic acid (D) allele (frequency = 0.034)
      was associated with increased risk for T2D (n = 4292, P = 2.0 * 10-5 adjusted for
      age, birth year, and the first 5 genetic principal components; odds ratio [OR] =
      2.23 [1.54-3.23] per risk allele) and an earlier age of T2D onset (n = 4292, P =
      2 * 10-4 , hazard rate ratio = 1.45 [1.20-1.75], Psex interaction = 0.05). Female
      carriers of the D-allele also had lower birth weight (n = 1313, beta = -163 g, P
      = .006, Psex interaction = 0.008). Among 85 siblings discordant for G310D,
      carriers of the D-allele had shorter stature as compared with carriers of the G
      allele (beta = -1.6 cm, P = .001, within family model). The G310D variant was
      functionally studied in vitro, where the D-allele had a 22% increase (P = .0005)
      in FOXO1-induced transcriptional activity, due to decreased activation of the
      PI3K/AKT pathway mediated through reduced IGF1R activity. CONCLUSION: A unique
      G310D variant in IGF1R, which occurs in 6% American Indians, may impair IGF1R
      signalling pathways, thereby increasing the risk of T2D.

PMID- 29470851
TI  - The Relation between Descriptive Norms, Suicide Ideation, and Suicide Attempts
      among Adolescents.
AB  - This study examined the relationship between adolescents' beliefs about the
      prevalence of youth suicide ideation (ideation descriptive norms) and suicide
      attempts (attempt descriptive norms) with self-reported suicide ideation and
      attempts. Descriptive norms, suicide ideation, and suicide attempts as well as
      gender, race/ethnicity, and exposure to family, peer, and others' suicide were
      assessed in 2,109 students at six suburban New York State high schools. After
      controlling for demographic variables and exposure to suicide, elevated ideation
      descriptive norms and attempt descriptive norms were associated with higher rates
      of suicide ideation and lifetime suicide attempts among adolescents. Adolescents
      who believed suicide ideation and attempts to be more widespread among peers
      (i.e., elevated ideation and attempt descriptive norms) were more likely to
      endorse suicide ideation and attempts. Correcting these descriptive norms may be
      a worthwhile goal for school-based suicide prevention programs.

PMID- 29470853
TI  - "How, of All The Millions of People...": Re-Examination of a Question From an
      Early MRI Research Project.
AB  - "How, of all the millions of people in the world, did the two of you get
      together?", a question to be addressed conjointly to a couple, part of a
      Structure Family Interview developed during the early heydays of the Mental
      Research Institute at Palo Alto, California, is analyzed in terms of structure,
      process and outcome of responses to it, and discussed as a powerful research and
      clinical tool with current potentials, as it provides in a succinct fashion
      remarkable insights into a narrative that is constitutive of the couple and, by
      omission or commission, revealing in terms of the couple's evolution.

PMID- 29470852
TI  - High-quality human and rat spermatozoal RNA isolation for functional genomic
      studies.
AB  - Sperm RNA is a sensitive monitoring endpoint for male reproductive toxicants, and
      a potential biomarker to assess male infertility and sperm quality. However,
      isolation of sperm RNA is a challenging procedure due to the heterogeneous
      population of cells present in the ejaculate, the low yield of RNA per
      spermatozoon, and the absence of 18S and 28S ribosomal RNA subunits. The unique
      biology of spermatozoa has created some uncertainty in the field about RNA
      isolation methods, indicating the need for rigorous quality control checks to
      ensure reproducibility of data generated from sperm RNA. Therefore, we developed
      a reliable and effective protocol for RNA isolation from rat and human
      spermatozoa that delivers highly purified and intact RNA, verified using RNA
      specific electrophoretic chips and molecular biology approaches such as RT-PCR
      and Western blot analysis. The sperm RNA isolation technique was optimized using
      rat spermatozoa and then adapted to human spermatozoa. Three steps in the sperm
      isolation procedure, epididymal fluid collection, sperm purification, and
      spermatozoon RNA extraction, were evaluated and assessed. The sperm RNA
      extraction methodology consists of collection of rat epididymal fluid with
      repeated needle punctures of the epididymis, somatic cell elimination using
      detergent-based somatic cell lysis buffer (SCLB) and the use of RNA isolation
      Kit. Rat sperm heads are more resistant to disruption than human spermatozoa,
      necessitating the addition of mechanical lysis with microbeads and heat in the
      rat protocol, whereas the human sperm protocol only required lysis buffer. In
      conclusion, this methodology results in reliable and consistent isolation of high
      quality sperm RNA. Using this technique will aid in translation of data collected
      from animal models, and reproducibility of clinical assessment of male factor
      fertility using RNA molecular biomarkers.

PMID- 29470854
TI  - The Cost-Effectiveness of Screening in the Community to Reduce Osteoporotic
      Fractures in Older Women in the UK: Economic Evaluation of the SCOOP Study.
AB  - The SCOOP study was a two-arm randomized controlled trial conducted in the UK in
      12,483 eligible women aged 70 to 85 years. It compared a screening program using
      the FRAX(r) risk assessment tool in addition to bone mineral density (BMD)
      measures versus usual management. The SCOOP study found a reduction in the
      incidence of hip fractures in the screening arm, but there was no evidence of a
      reduction in the incidence of all osteoporosis-related fractures. To make
      decisions about whether to implement any screening program, we should also
      consider whether the program is likely to be a good use of health care resources,
      ie, is it cost-effective? The cost per gained quality adjusted life year of
      screening for fracture risk has not previously been demonstrated in an economic
      evaluation alongside a clinical trial. We conducted a "within trial" economic
      analysis alongside the SCOOP study from the perspective of a national health
      payer, the UK National Health Service (NHS). The main outcome measure in the
      economic analysis was the cost per quality adjusted life year (QALY) gained over
      a 5-year time period. We also estimated cost per osteoporosis-related fracture
      prevented and the cost per hip fracture prevented. The screening arm had an
      average incremental QALY gain of 0.0237 (95% confidence interval -0.0034 to
      0.0508) for the 5-year follow-up. The incremental cost per QALY gained was L2772
      compared with the control arm. Cost-effectiveness acceptability curves indicated
      a 93% probability of the intervention being cost-effective at values of a QALY
      greater than L20,000. The intervention arm prevented fractures at a cost of L4478
      and L7694 per fracture for osteoporosis-related and hip fractures, respectively.
      The current study demonstrates that a systematic, community-based screening
      program of fracture risk in older women in the UK represents a highly cost
      effective intervention. (c) 2018 The Authors. Journal of Bone and Mineral
      Research Published by Wiley Periodicals, Inc.

PMID- 29470855
TI  - Role of the Open-Shell Character on the Pressure-Induced Conductivity of an
      Organic Donor-Acceptor Radical Dyad.
AB  - Single-component conductors based on neutral organic radicals have received a lot
      of attention due to the possibility that the unpaired electron can serve as a
      charge carrier without the need of a previous doping process. Although most of
      these systems are based on delocalized planar radicals, we present here a
      nonplanar and spin localized radical based on a tetrathiafulvalene (TTF) moiety,
      linked to a perchlorotriphenylmethyl (PTM) radical by a conjugated bridge, which
      exhibits a semiconducting behavior upon application of high pressure. The
      synthesis, electronic properties, and crystal structure of this neutral radical
      TTF-Ph-PTM derivative (1) are reported and implications of its crystalline
      structure on its electrical properties are discussed. On the other hand, the non
      radical derivative (2), which is isostructural with the radical 1, shows an
      insulating behavior at all measured pressures. The different electronic
      structures of these two isostructural systems have a direct influence on the
      conducting properties, as demonstrated by band structure DFT calculations.

PMID- 29470856
TI  - Leishmania donovani inhibits ferroportin translation by modulating FBXL5-IRP2
      axis for its growth within host macrophages.
AB  - Hepcidin mediated ferroportin (Fpn) degradation in macrophages is a well adopted
      strategy to limit iron availability towards invading pathogens. Leishmania
      donovani (LD), a protozoan parasite, resides within macrophage and competes with
      host for availing iron. Using in vitro and in vivo model of infection, we reveal
      that LD decreases Fpn abundance in host macrophages by hepcidin independent
      mechanism. Unaffected level of Fpn-FLAG in LD infected J774 macrophage confirms
      that Fpn down-regulation is not due its degradation. While increased Fpn mRNA but
      decreased protein expression in macrophages suggests blocking of Fpn translation
      by LD infection that is confirmed by 35 S-methionine labelling assay. We further
      reveal that LD blocks Fpn translation by induced binding of iron regulatory
      proteins (IRPs) to the iron responsive element present in its 5'UTR. Supershift
      analysis provides evidence of involvement of IRP2 particularly during in vivo
      infection. Accordingly, a significant increase in IRP2 protein expression with
      simultaneous decrease in its stability regulator F-box and leucine-rich repeat
      Protein 5 (FBXL5) is detected in splenocytes of LD-infected mice. Increased
      intracellular growth due to compromised expressions of Fpn and FBXL5 by specific
      siRNAs reveals that LD uses a novel strategy of manipulating IRP2-FBXL5 axis to
      inhibit host Fpn expression.

PMID- 29470857
TI  - Numerical study on the hemodynamics of patient-specific carotid bifurcation using
      a new mesh approach.
AB  - The definition of a suitable mesh to simulate blood flow in the human carotid
      bifurcation has been investigated. In this research, a novel mesh generation
      method is proposed: hexahedral cells at the center of the vessel and a fine grid
      of tetrahedral cells near the artery wall, in order to correctly simulate the
      large blood velocity gradients associated with specific locations. The selected
      numerical examples to show the pertinence of the novel generation method are
      supported by carotid ultrasound image data of a patient-specific case. Doppler
      systolic blood velocities measured during ultrasound examination are compared
      with simulated velocities using 4 different combinations of hexahedral and
      tetrahedral meshes and different fluid dynamic simulators. The Lin's test was
      applied to show the concordance of the results. Wall shear stress-based
      descriptors and localized normalized helicity descriptor emphasize the
      performance of the new method. Another feature is the reduced computation time
      required by the developed methodology. With the accurate combined mesh, different
      flow rate partitions, between the internal carotid artery and external carotid
      artery, were studied. The overall effect of the partitions is mainly in the blood
      flow patterns and in the hot-spot modulation of atherosclerosis-susceptible
      regions, rather than in their distribution along the bifurcation.

PMID- 29470859
TI  - Added value of second biopsy target in screen-detected widespread suspicious
      breast calcifications.
AB  - INTRODUCTION: There is controversy on the optimal work-up of screen-detected
      widespread breast calcifications: whether to biopsy a single target or multiple
      targets. This study evaluates agreement between multiple biopsy targets within
      the same screen-detected widespread (>=25 mm) breast calcification to determine
      if the second biopsy adds value. METHODS: Retrospective observational study of
      women screened in a statewide general population risk breast cancer mammographic
      screening program from 2009 to 2016. Screening episodes recalled for widespread
      calcifications where further views indicated biopsy, and two or more separate
      target areas were sampled within the same lesion were included. Percentage
      agreement and Cohen's Kappa were calculated. RESULTS: A total of 293317 women
      were screened during 761124 separate episodes with recalls for widespread
      calcifications in 2355 episodes. In 171 women, a second target was biopsied
      within the same lesion. In 149 (86%) cases, the second target biopsy result
      agreed with the first biopsy (kappa = 0.6768). Agreement increased with
      increasing mammography score (85%, 86% and 92% for score 3, 4 and 5 lesions).
      Same day multiple biopsied lesions were three times more likely to yield
      concordant results compared to post-hoc second target biopsy cases. CONCLUSION:
      While a single target biopsy is sufficient to discriminate a benign vs. malignant
      diagnosis in most cases, in 14% there is added value in performing a second
      target biopsy. Biopsies performed prospectively are more likely to yield
      concordant results compared to post-hoc second target biopsy cases, suggesting a
      single prospective biopsy may be sufficient when results are radiological
      pathological concordant; discordance still requires repeat sampling.

PMID- 29470858
TI  - Genes affecting progression of bacteriophage P22 infection in Salmonella
      identified by transposon and single gene deletion screens.
AB  - Bacteriophages rely on their hosts for replication, and many host genes
      critically determine either viral progeny production or host success via phage
      resistance. A random insertion transposon library of 240,000 mutants in
      Salmonella enterica serovar Typhimurium was used to monitor effects of individual
      bacterial gene disruptions on bacteriophage P22 lytic infection. These
      experiments revealed candidate host genes that alter the timing of phage P22
      propagation. Using a False Discovery Rate of < 0.1, mutations in 235 host genes
      either blocked or delayed progression of P22 lytic infection, including many
      genes for which this role was previously unknown. Mutations in 77 genes reduced
      the survival time of host DNA after infection, including mutations in genes for
      enterobacterial common antigen (ECA) synthesis and osmoregulated periplasmic
      glucan (OPG). We also screened over 2000 Salmonella single gene deletion mutants
      to identify genes that impacted either plaque formation or culture growth rates.
      The gene encoding the periplasmic membrane protein YajC was newly found to be
      essential for P22 infection. Targeted mutagenesis of yajC shows that an
      essentially full-length protein is required for function, and potassium efflux
      measurements demonstrated that YajC is critical for phage DNA ejection across the
      cytoplasmic membrane.

PMID- 29470860
TI  - Investigation of the in vivo metabolism of harpagoside and distribution of its
      metabolites in rats by HPLC-IT-TOF-MSn.
AB  - Harpagoside, an iridoid glycoside, is the major bioactive constituent of the
      traditional Chinese medicine Scrophulariae Radix. High-performance liquid
      chromatography with a diode array detector combined with electrospray ionization
      ion trap time-of-flight multistage mass spectrometry (HPLC-ESI-IT-TOF-MSn ) was
      used to profile and identify the metabolites of harpagoside in rats in vivo and
      to study the distribution of these metabolites in rats for the first time. A
      total of 45 metabolites were identified, 37 of which were postulated to be new
      compounds. The number of detected metabolites in the heart, liver, spleen, lung,
      kidney, stomach and small intestine was 2, 9, 6, 16, 4, 16 and 6, respectively,
      which indicated that the target organs of harpagoside should be spleen, lung and
      stomach. The main types of metabolic reactions of harpagoside in rats are
      hydrolysis, reduction, sulfuric acid addition, hydroxylation, methoxylation,
      sulfate substitution, methylation, glucose conjugation and amino acid
      conjugation. Furthermore, 23 metabolites were determined to have bioactivities
      based on the literature and 'PharmMapper' analysis. These findings are useful for
      better comprehension of the effective forms, target organs and pharmacological
      effects of harpagoside. Moreover, these findings provide a reference for studying
      the metabolism and distribution of iridoid compounds.

PMID- 29470861
TI  - Mini-Cog for the diagnosis of Alzheimer's disease dementia and other dementias
      within a primary care setting.
AB  - BACKGROUND: Alzheimer's disease and other forms of dementia are becoming
      increasingly common with the aging of most populations. The majority of
      individuals with dementia will first present for care and assessment in primary
      care settings. There is a need for brief dementia screening instruments that can
      accurately diagnose dementia in primary care settings. The Mini-Cog is a brief,
      cognitive screening test that is frequently used to evaluate cognition in older
      adults in various settings. OBJECTIVES: To determine the diagnostic accuracy of
      the Mini-Cog for diagnosing Alzheimer's disease dementia and related dementias in
      a primary care setting. SEARCH METHODS: We searched the Cochrane Dementia and
      Cognitive Improvement Register of Diagnostic Test Accuracy Studies, MEDLINE,
      Embase and four other databases, initially to September 2012. Since then, four
      updates to the search were performed using the same search methods, and the most
      recent was January 2017. We used citation tracking (using the databases' 'related
      articles' feature, where available) as an additional search method and contacted
      authors of eligible studies for unpublished data. SELECTION CRITERIA: We only
      included studies that evaluated the Mini-Cog as an index test for the diagnosis
      of Alzheimer's disease dementia or related forms of dementia when compared to a
      reference standard using validated criteria for dementia. We only included
      studies that were conducted in primary care populations. DATA COLLECTION AND
      ANALYSIS: We extracted and described information on the characteristics of the
      study participants and study setting. Using the Quality Assessment of Diagnostic
      Accuracy Studies (QUADAS-2) criteria we evaluated the quality of studies, and we
      assessed risk of bias and applicability of each study for each domain in QUADAS
      2. Two review authors independently extracted information on the true positives,
      true negatives, false positives, and false negatives and entered the data into
      Review Manager 5 (RevMan 5). We then used RevMan 5 to determine the sensitivity,
      specificity, and 95% confidence intervals. We summarized the sensitivity and
      specificity of the Mini-Cog in the individual studies in forest plots and also
      plotted them in a receiver operating characteristic plot. We also created a 'Risk
      of bias' and applicability concerns graph to summarize information related to the
      quality of included studies. MAIN RESULTS: There were a total of four studies
      that met our inclusion criteria, including a total of 1517 total participants.
      The sensitivity of the Mini-Cog varied between 0.76 to 1.00 in studies while the
      specificity varied between 0.27 to 0.85. The included studies displayed
      significant heterogeneity in both methodologies and clinical populations, which
      did not allow for a meta-analysis to be completed. Only one study (Holsinger
      2012) was found to be at low risk of bias on all methodological domains. The
      results of this study reported that the sensitivity of the Mini-Cog was 0.76 and
      the specificity was 0.73. We found the quality of all other included studies to
      be low due to a high risk of bias with methodological limitations primarily in
      their selection of participants. AUTHORS' CONCLUSIONS: There is a limited number
      of studies evaluating the accuracy of the Mini-Cog for the diagnosis of dementia
      in primary care settings. Given the small number of studies, the wide range in
      estimates of the accuracy of the Mini-Cog, and methodological limitations
      identified in most of the studies, at the present time there is insufficient
      evidence to recommend that the Mini-Cog be used as a screening test for dementia
      in primary care. Further studies are required to determine the accuracy of Mini
      Cog in primary care and whether this tool has sufficient diagnostic test accuracy
      to be useful as a screening test in this setting.

PMID- 29470862
TI  - Arabidopsis HIPP27 is a host susceptibility gene for the beet cyst nematode
      Heterodera schachtii.
AB  - Sedentary plant-parasitic cyst nematodes are obligate biotrophs that infect the
      roots of their host plant. Their parasitism is based on the modification of root
      cells to form a hypermetabolic syncytium from which the nematodes draw their
      nutrients. The aim of this study was to identify nematode susceptibility genes in
      Arabidopsis thaliana and to characterize their roles in supporting the parasitism
      of Heterodera schachtii. By selecting genes that were most strongly upregulated
      in response to cyst nematode infection, we identified HIPP27 (HEAVY METAL
      ASSOCIATED ISOPRENYLATED PLANT PROTEIN 27) as a host susceptibility factor
      required for beet cyst nematode infection and development. Detailed expression
      analysis revealed that HIPP27 is a cytoplasmic protein and that HIPP27 is
      strongly expressed in leaves, young roots and nematode-induced syncytia. Loss-of
      function Arabidopsis hipp27 mutants exhibited severely reduced susceptibility to
      H. schachtii and abnormal starch accumulation in syncytial and peridermal
      plastids. Our results suggest that HIPP27 is a susceptibility gene in Arabidopsis
      whose loss of function reduces plant susceptibility to cyst nematode infection
      without increasing the susceptibility to other pathogens or negatively affecting
      the plant phenotype.

PMID- 29470863
TI  - The evolution of mollusc shells.
AB  - Molluscan shells are externally fabricated by specialized epithelial cells on the
      dorsal mantle. Although a conserved set of regulatory genes appears to underlie
      specification of mantle progenitor cells, the genes that contribute to the
      formation of the mature shell are incredibly diverse. Recent comparative analyses
      of mantle transcriptomes and shell proteomes of gastropods and bivalves are
      consistent with shell diversity being underpinned by a rapidly evolving mantle
      secretome (suite of genes expressed in the mantle that encode secreted proteins)
      that is the product of (a) high rates of gene co-option into and loss from the
      mantle gene regulatory network, and (b) the rapid evolution of coding sequences,
      particular those encoding repetitive low complexity domains. Outside a few
      conserved genes, such as carbonic anhydrase, a so-called "biomineralization
      toolkit" has yet to be discovered. Despite this, a common suite of protein
      domains, which are often associated with the extracellular matrix and immunity,
      appear to have been independently and often uniquely co-opted into the mantle
      secretomes of different species. The evolvability of the mantle secretome
      provides a molecular explanation for the evolution and diversity of molluscan
      shells. These genomic processes are likely to underlie the evolution of other
      animal biominerals, including coral and echinoderm skeletons. This article is
      categorized under: Comparative Development and Evolution > Regulation of Organ
      Diversity Comparative Development and Evolution > Evolutionary Novelties.

PMID- 29470864
TI  - Styrene Polymerization under Ambient Conditions by using a Transient 1,3,2
      Diazaphospholane-2-oxyl Complex.
AB  - A combined theoretical and experimental study on the formation and reactivity of
      a P-OTEMP (P-bound TEMPO (TEMPO=2,2,6,6-tetramethyl-piperidin-1-oxyl))
      substituted 1,3,2-diazaphospholane W(CO)5 complex is presented, including DFT
      based mechanistic details. The complex possesses a thermally labile O-N bond that
      cleaves homolytically yielding the transient 1,3,2-diazaphospholane-2-oxyl
      complex [(CO)5 W(R2 PO. )], which acts as a radical initiator for styrene
      polymerization under ambient conditions.

PMID- 29470865
TI  - [Not Available.]
AB  - The purpose of this article is to provide a review on Human cytomegalovirus (CMV)
      in pregnancy. Approximately 10% of congenitally infected infants have symptoms of
      disease at birth: sensorineural hearing loss, mental retardation, microcephaly,
      development delay, seizure disorders, and cerebral palsy. We discuss epidemiology
      of congenital CMV and the prevention, diagnosis, prognosis, and management CMV in
      pregnancy and congenital CMV infection.

PMID- 29470866
TI  - [UTERINE SCAR DEFECT IN WOMEN AFTER CESAREAN SECTION - ULTRASOUND AND
      HYSTEROSCOPIC DIAGNOSI.]
AB  - : The aim of our study was to determine the frequency of defect scar in women
      with clinical complaints after Cesarean section (CS) diagnosed by transvaginal
      ultrasonography and diagnostic hysteroscopy as well as to determine the degree of
      match between the data obtained by the two methods. MATERIALS AND METHODS: The
      study was retrospective and was conducted in the Department of General Oncology
      and Gynecology, MMA for the period from 2014 to 2016 years. Included are 25 non
      pregnant premenopausal women aged 29 to 45 years with clinical symptoms. The main
      inclusion criteria were delivery by CS, overt clinical gynecological symptoms and
      positive imaging findings of a defect in the scar. The main gynecological
      symptoms are: postmenstrual and breakthrough bleeding, dysmenorrhea, dispaureny
      and idiopathic pain over the symphysis. Imaging studies were performed using two
      dimensional transvaginal sonography and diagnostic hysteroscopy. The data are
      processed by Social statistic STAT 10. We used Chi square statistic test 12.5
      (Pearson). Data were compared to two independent groups. Results were
      statistically significant at values of p<0. 05. RESULTS: The most common symptom
      in women included in the study was a post-menstrual bleeding - 22 (88 %). In 15
      (60 %) of them we found out ultrasound signs of a defect in uterine scar (p =0,
      00407). In 10 (40%) of those patients by diagnostic hysteroscopy we found
      defective scar (p=0, 000004). There has been no significant difference between
      the two methods in terms of accuracy of diagnosis (isthmocele) (p=0.1572)
      although the hysteroscopy there was a statistically higher one. CONCLUSION: With
      increasing frequency of cesarean section (CS) increases and frequency of early
      and late complications of this surgery. Irregular uterine bleeding in women after
      CS and a lack of other organic causes are the result of a defect in uterine scar.
      First choice for the diagnosis of this type of pathology is ultrasonography
      examination followed by diagnostic hysteroscopy. It is conducting further studies
      on the etiology of this complication.

PMID- 29470867
TI  - [FREQUENCY OF PRETERM BIRTH IN WOMEN WITH CERVICAL VAGINAL INFECTIONS.]
AB  - Premature birth (PB) occurs in 5% to 18% of births in the world. Children born
      prematurely are at increased risk of death, major neonatal complications, long
      term adverse consequences for health and development. The cause of spontaneous
      preterm birth is often unknown, but it is believed that intrauterine infection is
      implicated in 40% of cases. The most likely route to intrauterine infection is
      ascending infection of the genital tract. Infection of the genital tract is more
      common in women with spontaneous preterm births in lower ge. tational age. s
      performed a retrospective research of 70 pregnant women and their newborns. In
      the group with preterm birth was reported high percentage of CVI - 37.14%, while
      in the control group this percentage is 17.14%. The results showed the increase
      in the incidence of CVI group of PB more than twice. There is a need an effective
      prevention and treatment of CVI during pregnancy. The timely detection of
      deviations from normal vaginal microflora and the correct therapeutic approach
      would reduce the risks of PB and infectious complications in newborns.

PMID- 29470868
TI  - [Not Available.]
AB  - Anemia is one of the most frequent pathologic conditions during pregnancy and
      puerperium. WHO define anemia according to blood hemoglobin levels. Severe anemia
      in pregnancy is associated with a higher risk of preterm birth and intrauterine
      retardation and other complications during pregnancy. It remains a major
      contributing factor to maternal morbidity and mortality, especially in developing
      countries. Iron deficiency anemia in pregnancy is a common disorder; even in
      countries with their favorable socioeconomic conditions. In the majority of
      cases, it is preexistent and can be aggravated during pregnancy. Even with
      optimal nutrition pregnancy is characterized by a negative iron balance. Defining
      the type of anemia is necessary for its adequate treatment.

PMID- 29470869
TI  - [ASPHYXIA IN INTRAUTERINE GROWTH RESTRICTION OF THE FETUS- CARDIOTOCOGRAPHY AND
      ULTRASOUND METHODS OF DIAGNOSIS.]
AB  - Fetal asphyxia remains an important cause of neonatal morbidity and mortality.
      The tests in themselves (cardiotocography (NST), sonography, Doppler studies)
      which are used for antenatal fetus surveillance are aimed at timely diagnosing
      the signs of the fetus asphyxia. The objective of the current research is to
      study which modifications in the cardiotocography (NST), arterial and venosus
      Doppler correlate most strongly with severe asphyxia pH< 7.10 and BE>=12 mmol/l
      regarding pregnancies which are complicated with intrauterine growth restriction
      of the fetus. The presence of spontaneous decelerations in the cardiotocography
      shows sensitivity 81.3%, specificity 97.1%, positive predictive value (PPV) 83.2,
      negative predictive value (NPV) 98.2%, odds ratio (OR) 260, p< 0.0001, the
      reversed blood velocity of artery umbilicalis shows sensitivity 58.3%,
      specificity 96.2%, PPV 63.6%, NPV 95. 3% OR 35.7 p< 0.001, reversed a-wave ductus
      venosus shows sensitivity 51%, specificity 94.3%, PPV 48% NPV 93.2% OR 16.7, p<
      0.001. Concerning pregnant women with intrauterine growth restriction of the
      fetus the prognostication of severe fetus asphyxia at delivery - pH<7. 10 and BE 
      12 mmol/I with the highest specificity of antenatal testing is the occurrence of
      spontaneous decelerations in NST, the reversed blood velocity of umbilical artery
      and the reversed a-wave ductus venosus in Doppler studies.

PMID- 29470870
TI  - [(DIASTOLIC DECELERATIONTIME - DDT).]

PMID- 29470871
TI  - [Not Available.]
AB  - Although the precise pathophysiology of pre-eclampsia remains unknown, this
      condition continues to be a major cause of maternal and fetal mortality and
      morbidity. Early prediction of pre-eclampsia would allow for timely initiation of
      preventive therapy A combination of biophysical and biochemical markers are
      superior to other tests for early prediction of the development of pre-eclampsia.
      This article reviews the current research of the most important strategies for
      prediction of pre-eclampsia, including the use of maternal risk factors, mean
      maternal arterial pressure, ultrasound parameters, and biomarkers.

PMID- 29470872
TI  - [Not Available.]
AB  - A short overview of hemorrhagic shock in pregnancy, childbirth and postpartum
      period are presented data from major and recent developments on the subject.
      Presented a clinical case - pregnant with complications and hemorrhagic shock.

PMID- 29470873
TI  - [in - process.]

PMID- 29470874
TI  - [In-process.]

PMID- 29470875
TI  - [In-process.]

PMID- 29470876
TI  - [A histological unexpected finding.]

PMID- 29470877
TI  - [Epigastric pain and extraluminal retroperitoneal gas.]

PMID- 29470878
TI  - [Cost-effectiveness of screening for colorectal cancer in Argentina.]
AB  - : International evidence show that screening for colorectal cancer is cost
      effective; however, in Argentina is unknown. OBJECTIVE: The study shows the
      results of a cost-effectiveness evaluation based on two alternative mechanisms:
      annual faecal immunochemical testing (FIT), and colonoscopy every ten years in
      Argentina. METHODS: The study develops a Mar- kov model in ten stages, based on
      information provided by the INC, prior literature review and on-line
      questionnaires to physicians enrolled in the four major scientific societies
      related to cancer. Cost information arrived from the Na- tional Superintendence
      of Social Health Insurances and a sample of managers in social and private
      insurance schemes. RESULTS: The most cost-effective strategy consisted annual
      FIT, in comparison no intervention and colonoscopy every 10 years. The
      incremental cost effectiveness ratio (ICER) of FIT versus no intervention was of
      980.5 pesos per QALY The findings were robust to deterministic sensitivity
      analysis. CONCLUSIONS: We confirmed that screening for CRC is a cost-effective
      intervention. Whereas the CCR is one of the leading causes of mortality in
      Argentina, these results support the widespread use of screening for CRC using
      anual FIT which proves to be highly cost effective for the country.

PMID- 29470879
TI  - [Patient-Related Factors Affecting Bowel Preparation Prior to Colonoscopy.]
AB  - INTRODUCTION: Colorectal cancer is a major health problem worldwide because it is
      the third most common cancer and the third leading cause of cancer mortality in
      western countries. Screening for colorectal cancer in asymptomatic patients is
      crucialfor reducing the incidence and colonoscopy is one of the methods of
      choice. The ability of colonoscopy in detecting small lesions is clearly
      influenced by the quality of the colonic preparation. OBJECTIVES: To know which
      are the variablesrelating to the patient and the type ofpreparation that affect
      the quality of colonic cleansing. MATERIALS AND METHODS: It was designed a cross
      sectional study. It was administered a questionnaire for the enrolled subjects to
      assess the presence offactors that could affect the quality of colonic cleansing.
      Then they underwent a colonoscopy. The different variables between subjects with
      adequate or inadequate colonic cleansing were compared. RESULTS: We evaluated 277
      subjects. In multivariate analysis the only variables that showed significant
      differences are split dose [OR 0.45 (0.21 to 0.99)] and age [OR 1.02 (1-1.05)].
      Obesity showed no significant differences in multivariate analysis [OR 1.84 (0.9
      3.78)]. CONCLUSIONS: Age and split-dose were the only variables significantly
      associated with the quality of bowel preparation prior to colonoscopy. Not so
      constipation or the presence ofdiverticula, so these patients do not require
      special preparation regimes.

PMID- 29470880
TI  - [Flexible endoscopic treatment for Zenker's diverticulum: preliminary results in
      a single center experience in a public hospital in Argentina.]
AB  - : Zenker's diverticulum (ZD) is an acquired protrusion of the esophageal wall.
      Treatment is reservedfor symptomatic cases. In Argentina, ZD has historically
      managed exclusively by surgical intervention. In 1995, Ishioka, et al and Mulder,
      et a1published their experience using flexible endoscopes for diverticulotomy.
      Since then, a wide variety ofdifferent techniques have been published. Objetive.
      To present technique modifications and results ofour center. MATERIAL AND
      METHODS: We reviewed the database of57patients (36 men), with a mean age of 71.9
      years (range 37-98), with symptomatic Zenker ' diverticulum, who underwent
      endoscopic myotomy, from December 1997 to April 2015. All procedures were
      performed in our center, by the same endoscopist (HM). The most common symptom
      was dysphagia (94.7%), which was recorded by a 0-4 score (0=no dysphagia, 1
      =solids, 2=semisolids, 3=liquids, 4=saliva). The first nine cases were done
      exposing the septum with a nasogastric tube, and the others with a soft
      diverticuloscope. Allprocedures were carried out with the patient under deep
      sedation, adminis- tered by an anesthesiologist. A myotomy was done in all cases
      with a needle-knife, using a coagulation current, to prevent bleeding. Clips were
      placed to close mucosalilaps, decrease the risk of unsuspected perforation and
      postprocedure bleeding. RESULTS: Seventy procedures were performed, in 56
      patients. One patient was excluded because of incomplete myotomy due to a severe
      adverse event. Ninety-eight percent ofpatients had resolution or improvement of
      the dysphagia score, at 30 days. Three patients with regurgitation as their sole
      complaint completely resolved their symptom. Median follow-up was 25 months (1
      99). Thirty-seven patients were followed for at least 1 year and 97.3% showed a
      favorable outcome. In 13 cases (22.8%) a reintervention was needed, with positive
      results in all cases. Bleeding occurred in one patient (1.4%), who required
      surgery. Another patient required surgical intervention due to technical issues.
      There were no perforations or infections. CONCLUSION: Treatment of ZD with
      flexible endoscope is a safe and effective option, with good long-term results.
      We need randomized clinical trials comparing different therapeutic options to be
      able to recommend a definitive strategy. Until then, we suggest using the
      technique with which each center has the most experience and feels most
      comfortable performing.

PMID- 29470881
TI  - [Syncrhonous carcinosarcoma of the extrahepatic bile duct and gallbladder.]
AB  - : Carcinosarcoma is a malignant neoplasm characterized for intermingled
      epithelial and mesenchymal components. CASE REPORT: A preoperative suspected
      diagnosis will allow a radical therapy avoiding a very bad prognosis. We report
      on a male patient who was operated in our Service with diagnosis of synchronous
      carcinosarcoma of gallbladder and extrahepatic bile duct and a review of the
      Medical Literature. DISCUSSION: A gallblader carcinosarcoma showing extension
      into common bile duct is very rare, a carcinosarcoma of the bile duct is
      exceptional, and a synchronous carcinosarcoma ofthe bile duct and gallbladder has
      not been reported previously.

PMID- 29470882
TI  - [Severe acute hepatitis by delta virus superinfection: diagnostic significance of
      molecular biology.]
AB  - HDV infection may occur within a primary HBV infection (co-infection) or by sub
      sequent acquisition ofthe virus in patients with chronic hepatitis B
      (superinfection). Acute HDV infection is rarely diagnosed. Since cero conversion
      usually takes place about six weeks after viral infection, early diagnosis
      requires the use of direct diagnostic techniques, such as antigen HD V (HDAg)
      detection, or genomic amplification by means of molecular biology methods (RT
      PCR). Here were port the case of a patient with chronic HBV infection that
      develops a severe acute hepatitis due to VHD superinfec- tion only detected by
      molecular biology.

PMID- 29470883
TI  - [Pediatric gastrointestinal disorders at hight altitude. Report of two cases and
      review of literature.]
AB  - Upon ascending above 2500 meters sea level, the human body undergoes a series of
      physiological changes that have been studied during years. These changes
      undertake various systems including gastrointestinal tract, with diverse clinical
      manifestations, most mild and therefore little reported and are underdiagnosed.
      Two pediatric patients who atended to the Pediatric Unit of Gastroenterolog,
      Hepatolog and Nutrition (Gastronutriped) in Bogota, in whose we documented
      symptoms affecting gastrointestinal tract associated with high altitude.Regarding
      to these cases, a review of the available literature focusing on physiolog,
      clinical manifestations and feasible treatment was made. The final aim of this
      article is to sensitize to health care professionals working in cities located at
      high altitudes, to consider this entity as a differential diagnosis in children
      from places with lower altitude.

PMID- 29470884
TI  - Extensive mesenteric lipodystrophy of the left colon: case report and brief
      review of the literature.
AB  - Mesenteric lipodystrophy is a rare inflammatory process that predominantly
      affects mesenteric adipose tissue of the small bowell. Several mechanisms have
      been suggested as responsible for this entity although the precise etiolog
      remains unknown. The diagnosis is based on CT or MRI imaging and generally
      confirmed by surgical biopsies. Treatment is individualized and empiric and
      depends on disease stage and symptoms. We report a case of a 35-year-old male who
      was admitted to our hospital with a history of abdominal pain, constipation and a
      palpable mass in the left lower quadrant. Abdominal CT scan showed diffuse
      thickening of the descending and rectosigmoid colon, associated with increased
      density of the mesenteric fat. After failure ofan initial treat- ment with
      glucocorticoids, he underwent a laparoscopic sigmoidectomy. Histopatholog
      analysis revealed extensive stea- tonecrosis ofpericolonicfat and lipid
      ladenfoamy cells which was consistent with the diagnosis of mesenteric
      lipodystrophy. Clinical presentation and treatment as well as a brief review of
      the literature are discussed.

PMID- 29470885
TI  - [Inflammatory fibroid polyp as the cause of upper gastrointestinal bleeding.]
AB  - The inflammatory fibroid polyp or Vanek's tumor is a benign polypoid lesion that
      can be found in any section of the digestive tract. It is most frequently located
      in the stomach and when found in this organ, the symptoms include upper
      gastrointestinal bleeding (often silent), anemia and melena. The case described
      below, on the contrary, presents a gastric inflammatory fibroid polyp which
      developed acute upper gastrointestinal bleeding and required surgical treatment.

PMID- 29470886
TI  - [Pediatric acute liver failure. Working group of the Latinamerican Society of
      Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN).]
AB  - Pediatric acute liver failure is a syndrome ofsevere and sudden dysfunction of
      the hepatocytes which produces a failure in synthetic and detoxifyingfunction. It
      is an infrequent and severe disease butpotentiallyfatal, occurring in children
      with no prior history of liver disease. Etiology is related to the age and
      geographic region of the patient, recognizing the origin: metabolic, infectious,
      drug exposure, autoinmune, vascular and oncologic. Indeterminate cause where all
      the etiological search is negative, can range between 18 and 47%, depending on
      the center and access to the realization of etiological studies. The process
      which determines the liver injury is still not well known and is considered
      multifactorial. Essentially, it depends on host susceptibility, the cause and
      severity of the damage and the ability of liver regeneration. The clinical
      presentation depends on the etiology, which usually begins with an episode
      ofacute hepatitis, that in the following days or weeks presents unfavorable
      outcome, deepening jaundice, affecting the general state and presenting severe
      coagulopathy that characterizes the syndrome. The treatment consists of general
      measures which take into account the metabolic disorders, nutritional aspect, and
      the prevention and treatment of all complications that occur in the evolutionary
      course (infectious, neurological, etc). Besides it is also vital to implement the
      specific treatment of those diseases which can benefit from it (alloimmune
      hepatitis, galactosemia, tyrosinemia, herpes simplex infection, Wilson's disease,
      etc.). However, despite therapeutic advances, acute liver failure results in
      death or liver transplantation in over 45% ofcases.

PMID- 29470887
TI  - [PATHOPHISIOLOGY OF POSTINFARCTION ANEURYSM OF LEFT VENTRICLE.]
AB  - In this article, the definition of a heart attack postinfarction aneurysm of the
      left ventricle of the heart is given, describe the geometric changes to the left
      ventricle, proceeding transmural myocardial transferred after a heart attack,
      they were described the adaptive machinery of the organism on the whole way the
      anesthesiologist in process of the anesthesia can encounter; and also indicate
      the presence of a possible sources of pathological threatening the life
      arrhythmias. At the end of the article is given the evolution of the procedures
      of correction of the heart attack postinfarction aneurism left ventricle of
      conducting revascularization myocardial or without it.

PMID- 29470888
TI  - [DEXMEDETOMIDINE SEDATION DURING TRANSCATHETER AORTIC VALVE IMPLANTATION.]
AB  - THE AIM: to determine the efficacy and safety of dexmedetomidinefor sedation and
      analgesia during transcatheter aortic valve implantation (TA VI) withfemoral
      access. MATERIALS AND METHODS: the study included 34 high-risk surgical patients
      with "critical aortic stenosis". All patients underwent TAVI with femoral access.
      TAVI performed under local anaesthesia: in 18 cases - with midazolam-ketamine
      sedetion, in 16 cases - with dexmedetomidine sedation. The depth of sedation was
      evaluated by Richmond agitation-sedation scale (RASS) and Ramsay scale.
      Assessment includes frequency of complications arising during perioperative
      period. RESULTS: in dexmedetomidine group compared with a group of
      midazolam/ketamine was observed significantly greater median of sedation level
      with RASS and Ramsay scales (- 3.5 and -1.0, p=0,000004, 5.0 and 3.0,
      respectively, p=0,000001). There was a signficant decrease in rapid pacing
      episodes in dexmedetomidine group (p = 0.0005). In the structure of complications
      prevailed delirium, stroke, ventricularfibrillation. There were no significant
      differences in the incidence and nature of complications in the groups studied.
      Under midazolam/ ketamine trend toward increased incidence of delirium compared
      with a group of dexmedetomidine (6.16 % and 6.25 %, respectively, p =0.604).
      There was no significant difference in the duration of operation and anesthesia
      in the study groups (p=0.889, p=0.103). There were no significant differences in
      length of hospital-stay and in the length of ICU-stay in groups studied (p
      =0.243, p=0.899). CONCLUSIONS: Sedation with dexmedetomidine during TA VI with
      femoral access demonstrates its safety and effectiveness. Dexmedetomidine
      provides deep level of sedation with RASS and Ramsay scales without depression of
      respiratory function. There is a good tolerability of operation and good
      conditions for long-term use of transesophageal ECHO. In the context of ECHO
      monitoring further reduces the need for multiple rapid pacing (p = 0.0005), which
      may reduce frequency of delirium in elderly patients.

PMID- 29470889
TI  - [ACCREDITATION OF THE HEALTH PROFESSIONAL AS A LAUNCH PAD FOR CONTINUING MEDICAL
      EDUCATION.]
AB  - The rapid development of medical science and health care practice, the need to
      improve the quality of health care, the ongoing modernization of education was
      the basis for scientfic rationale and implementation of the system of continuous
      medical education, which will be gradually expanded to cover individuals who have
      undergone 2016 accredited specialist.

PMID- 29470890
TI  - [THE STANDARTIZATION OF TEACHING PRACTICAL SKILLS IN MEDICAL UNIVERSITY.]
AB  - The article discusses the experience of unification of the teaching of obligatory
      practical skills for medical students. The technology teaching skills using
      simulation equipment and the results of implementing the standard of teaching.
      The example of the control knowledge using a checklist.

PMID- 29470891
TI  - [ACTUAL QUESTIONS OF TEACHING PALLIATIVE CARE IN A SYSTEM OF FURTHER PROFESSIONAL
      EDUCATION.]
AB  - In response to the introduction ofpalliative care as a new kind of medical care
      in Russian Federation (Federal law No.323 from 21.11.2011), Russian Federation
      Health Ministry has taskedfurther educational institutions with teaching doctors
      about this new kind of care. I.M Sechenov First Moscow State Medical University
      has answered this plea in 2015 by introducing a new course focused on palliative
      care. The program of education was prepared in accordance with rec- ommendations
      of World Health Organization (WHO) and European Association for Palliative Care
      (EAPC). A special attention was paid to the pain relief communication skills and
      organization ofpalliative care for adults in ambulatory and stationary treatment.
      The program integrates different teaching methods including eLearning, trainings
      on pain relief and practical trainings on communication skills for interaction
      with palliative patients and their relatives using the technology of
      <<standardized patient>>.

PMID- 29470892
TI  - [ULTRASOUND IN ANESTHESIOLOGY AND INTENSIVE CARE: WHAT TO TEACH?]
AB  - Despite the fact that there is a wealth of experience of using ultrasound in
      medicine, its application in anesthesiology and critical care began relatively
      recently Ultrasound navigation can improve the quality of the invasive
      procedures. There were developed special protocols for critically ill patients,
      which helps to obtain the diagnosis at the bedside. Therefore all the world's
      leading societies and associations recommend to include the training of
      ultrasound technology in the education program for anesthesiologists and
      intensive care specialists. Society for Ultrasound in Anaesthesia recommended to
      acquire six competencies: ultrasound monitoring of the respiratory tract in
      anesthesiology and critical care medicine; ultrasound monitoring of the pleura
      and the lungs; focused echocardiography and intraoperative monitoring;
      catheterization of blood vessels under the control of ultrasound; ultrasound
      monitoring ofcritically ill patients; ultrasound navigation for regional
      anesthesia. Resident physician should have skills for ultrasound assistance
      during catheterization central veins and for ultrasound monitoring in critical
      ill patients to the extent of FAST protocol (level ofpractical skill "to be
      able'). Other topics should being studied at the level "to know". It is
      reasonable to hone practical skills on these competences as part ofpostgraduate
      continuing education program to the extent that is needed for specialist at his
      workplace.

PMID- 29470893
TI  - [INFLUENCED ARBEPOETINALFA TO REDUCE THE NUMBER OF BLOOD TRANSFUSION IN CHILDREN
      WITH NON-SYNDROMIC CRANIOSYNOSTOSIS.]
AB  - BACKGROUND: According to the literature, the prevalence of non-syndromic forms of
      craniosynostosis in children is very high. Given that the treatment of this
      pathology and surgery performed only at an early age of the child, the need for
      transfusion arise very often. THE AIM: To study the efficacy ofpreoperative use
      of darbepoetin alfa in combination with intraoperative normovolemic hemodilution
      to reduce the number of blood transfusions during surgery and in the early
      postoperative period. MATERIALS AND METHODS: The study included 70 children
      between the ages of 6 months up to 12 months, divided into two groups: a control
      group (n=34) without stimulation of erythropoiesis and the study group (n =36)
      using apre-stimulation oferythropoiesis darbepoetin alfa. RESULTS: In the control
      group, blood transfusion was performed in 79% of cases, compared with the test
      group-22% of cases. Also, the patients ofthe study group determined a
      statistically significant (p<0. 05) increase the level of red blood cells,
      hemoglobin and reticulocytes. CONCLUSION: In children up to a year with various
      forms ofnon-syndromic craniosynostosis preoperative stimulation of erythropoiesis
      in conjunction with normovolemic hemodilution reduces the number of blood
      transfusions 3 times, or to opt out of its holding.

PMID- 29470894
TI  - [TREATMENT OF SEVERE INTRAPATUM ASPHYXIA.]
AB  - THE AIM: Estimate of efficiency of newborns with severe birth asphyxia treatment
      using systemic therapeutic hypothermia. MATERIALS AND METHODS: a retrospective
      open-controlled clinical research with a resolution of the Ethics;Committee
      performed in 33 neonates born in asphyxia and treated at the NICU All newborns
      due to the presence of indications, overall controlled hypothermia was conducted
      according to the approved protocol, using the apparatus Allon 2001". RESULTS: The
      neurological status at admission: Sarnat II was detected in 60.6% (20) children;
      Sarnat III was detected in 39.4% (13) children. The correlation ofApgar scores
      with the most severe hypoxic ischemic encephalopathy. Pupillary reflexes
      admission absent in 48.5% (16) newborns. Convulsions within first hours of lfe
      were observed in 57.6% (19) newborns. Convulsions within I day of life were
      observed in 81.8 % (27) newborns. The correlation of the amniotic infection (AI)
      and meconium aspiration syndrome (MAS) treatment using high-frequency mechanical
      ventilation (p<0,05) and prolongation of mechanical ventilation for more than 5
      days (p<0,01). At the beginning of systemic hypothermia fraction of inspired
      oxygen (FiO2), mean airway pressure (MAP), respiratory rate (RR) were down to the
      12th hour of life and reaches a minimum at the end of the third day. These trends
      have been observed in children with MAS. The correlation of the use of high
      frequency mechanical ventilation using high doses ofcardiotonics and the
      transition to the infusion of epinephrine or norepinephrine (p <0.01).There were
      no deaths in the studying group. CONCLUSIONS: 1. Reliable predictor of the
      clinical outcomes severity of hypoxic-ischemic encephalopathy (HIE) by the end of
      the first month lf is the presence of convulsions within the first hour of lf
      (p<0. 03). 2. When comparing the evaluation on Apgar scale with the data of acid
      base balance and severity of HIE a significant correlation between the estimation
      at the first minute is I point and at the fifth minute 3 point and more severe pH
      shift, base deficiency, hyperlactatacidosis and severe HIE. 3. MAS and AI are the
      most frequent accompanying diseases that complicates the severity of newborn
      status causing prolonged artificial ventilation and the infusion ofcardiotonics.
      4. There is a decrease in all parameters of artficial lung ventilation to the
      twelfth hour life in early systemic hypothermia and reached minimum by the end of
      the third day.

PMID- 29470895
TI  - [PECULIARITIES OF ANESTHESIA DURING COCHLEAR IMPLANTATION IN PEDIATRICS.]
AB  - THE AIM: analysis of the use of laryngeal mask in anesthesia for cochlear
      implantation. MATERIALS AND METHODS: 10 patients aged from 1 year to 5 years were
      operated on according to the classical method KI with the use of laryngeal masks.
      As anesthesia was performed a balanced multimodal anesthesia by Sevoflurane and
      Fentanyl. RESULTS: The use of laryngeal masks in all 10 cases have gave the
      possible to avoid the use of muscle relaxants and to clear the threshold of
      detection of acoustic reflexes ofstapes musclestendon, and to reduce time of
      surgical intervention. A short time surgery provided rapid awakening of the
      patient, absence of nausea and vomiting in the early postoperative period.
      CONCLUSION: use of laryngeal mask airway is reduces the time of surgery, minimize
      the patient's trauma, reduce input anesthetic drugs and get good results
      intraoperative audiological testing.

PMID- 29470896
TI  - [THE IMPACT OF PERINATAL METABOLIC DISORDERS CHOICE MODE MECHANICAL VENTILATION
      IN NEWBORNS.]
AB  - THE AIM: To study the influence of perinatal metabolic disorders, metabolism on
      the choice of mode of artificial lung ventilation in newborns. MATERIALS AND
      METHODS: The study included 73 neonates with severe respiratory failure,
      therefore, all children underwent ALV Depending on the mode ofventilation,
      patients were divided into two groups: group 1 - 33 neonates who were at the
      beginning of treatment on a ventilator in the SIMV mode, then led to HFO
      ventilation; group 2 - 40 neonates who underwent only the SIMV The study used
      following research methods: analysis ofpregnancy anamnestic data; clinical
      assessment of the newborn's condition at birth including Apgar score (AS) on the
      1st minute after birth; registration of changes of mode and parameters of
      mechanical ventilation: a mathematical calculation of oxygenation index (0I);
      determination of triglycerides and cholesterol in the central venous blood of
      newborns in thefirst hours ofpostnatal life and on the 5th day of life Results:
      At birth the triglycerides level in the blood of newborns is reduced and didn't
      differ signicantly between the groups. Along with this,. the newborns of 1st
      group remained impaired oxygen status, severe hypoxia, progressive increase of 01
      not resolved in the conventional ventilation, which is an indication to lead the
      children to HFO ventilation. CONCLUSION: Asphyxia at birth, resistant to therapy,
      characterized by worsening hypoxemia, impaired lung function oxygenation, the
      increase of lactate in the blood, deep base deficiency, disorders of the
      metabolism of triglycerides and cholesterol and high oxygenation index are
      testimony to the high-frequency oscillatory ventilation. Pathogenetically
      justified the use of this kind of respiratory theory, not only during RDSN.

PMID- 29470897
TI  - [METABOLIC PREVENTION OF FAT EMBOLISM.]
AB  - THE AIM: to study the effect of solution with methionine "Remaxol" on metabolic
      disorders andfat embolism developing in severe combined trauma. MATERIALS AND
      METHODS: 544 patient with severe skeletal trauma were undergone to a prospective
      study of dynamics of fat embolism syndrome development depending on the inclusion
      in the program of infusion therapy drug "Remaxol". The dynamics of lactate,
      glucose, free fatty acids, globularia and the incidence offat embolism syndrome
      were analyzed. RESULTS: Corrective action drug with methionine "Remaxol" on
      hyperglycemia, hyperlactatemia, hyperlipemia and de- crease circulation offat
      globules, which is reflected in the decrease in the frequency of development
      offat embolism syndrome was identified. CONCLUSION: One of the proposed
      mechanisms reduce the risk offat embolism development is assumed restoration of
      endogenous carnitine synthesis with methionine and transport offree fatty acids
      in the cell and their subsequent inclusion in metabolic processes.

PMID- 29470898
TI  - [OBESITY AS A RISK FACTOR FOR MASSIVE POSTPARTUM HEMORRHAGE.]
AB  - INTRODUCTION: No mat analysis devoted to the study of obstetric hemorrhage due to
      obesity has not yet been carried out. Publications of the results of major
      studies on the subject have appeared recently. Only the multivariate analysis
      will make a reasonable conclusion about the causes that affect the outcome and
      assess the extent of the simultaneous influence on him of often interrelated
      reasons. THE AIM: To estimate the signficance of obesity as an independent risk
      factor for serious obstetric haemorrhage. MATERIALS AND METHODS: A retrospective
      cohort study ofpregnancy and childbirth outcomes of 24634 women in childbirth.
      Depending on the initial body mass index (BM) of the patients were allocated two
      groups: basic - 2140 obese women with control - 17937 patients with an initial BW
      of 18.5 to 24.9 kg / m2. In order to determine the significance of obesity as a
      riskfactor of massive blood loss midwife performed multivariate statistical
      analysis, including cluster analysis, multiple correlation, linear and non-linear
      regression, statistical quality control using control charts. RESULTS:
      Hypotension uterus has been a major factor in the development of massive blood
      loss. For the implementation of hypotonic uterine bleeding was necessary set of
      conditions, interacting with other causal factors affecting the outcome. The
      minimum combination of these factors is the combination of "obesity" + "somatic
      pathology" + "induction of labor," in which the OR of postpartum hemorrhage was
      8,57 [CI 95% 6,13-36,28], p < 0.001. It is also significant risk factors were
      fetal macrosomia, multiple pregnancy, abdominal method of delivery, the degree of
      obesity, the method of anesthesia and duration of the operation. OR to define
      obesity as an isolated risk factor for the implementation of massive blood loss
      was 1.18 [95% CI: 0,78-1,27], p > 0.05. DISCUSSION: The impact of obesity as an
      isolated causes massive obstetric hemorrhage was minimal, but is powerful
      potentiating factor in the outcome. CONCLUSION: Analysis of the causes of
      complications in childbirth did not confirm the possibility of considering
      obesity as an independent risk factor for massive blood loss.

PMID- 29470899
TI  - [PERIOPERATIVE MANAGEMENT OF PATIENTS WITH DIABETES MELLITUS.]
AB  - The article is devoted to the existence of the problem of intraoperative provide
      patients with concomitant diabetes mellitus: a disease is not diagnosed in time,
      it increases the probability of death in the performance of surgery by 50%, where
      as the timely prevention and preparation reduces the chance of developing
      specific complications to the level of patients with the general population. The
      paper discusses the recommendations developed by the British Association
      ofEndocrinologists 2011 and Russia in 2015, as well as the Association
      ofAnaesthetists of Great Britain and Ireland (2015), provides practical
      recommendations for the preoperative preparation, anesthetic and resuscitation
      provide patients with concomitant diabetes mellitus.

PMID- 29470900
TI  - [PROGNOSTIC SIGNIFICANCE OF CHANGES OF BLOOD GLUCOSE LEVEL IN PATIENTS WITH
      THORACOABDOMINAL INJURIES.]
AB  - : Background Currently, one of the causes of high morbidity and mortality is
      injuries. Predict the outcome of injuries - it is an important task of the
      treating physician. Trauma is a stress factor so to predict the outcome, you can
      use markers of stress, the most accessible ofwhich is blood glucose. THE AIM: to
      reveal the dynamics of the relationship between blood glucose levels and the
      outlook for the life ofpatients with thoracoabdominal injuries. MATERIALS AND
      METHODS: A retrospective analysis of medical records of hospitalized patients
      were divided into two groups, depending on the outlook for the life of (favorable
      or unfavorable), and each of the groups - into two subgroups according to the
      presence or absence of signs of intoxication at admission. The subgroups were
      calculated and compared the mean blood glucose levels at different hours of
      hospital treatment. RESULTS: It was found that the average blood glucose levels
      at various hours of hospital stay were significantly higher in patients with poor
      outcome. The most noticeable was the difference in the first days of hospital
      treatment. Signs of intoxication was associated with lower values of glucose and
      a tendency to hypoglycaemia. In addition, among patients with high blood glucose
      ( 8 mg / dL) was observed over deaths in the first day of hospital stay.
      CONCLUSION: High blood glucose levels ( 8,0 mmol / L) in the first day of
      hospital treatment is a predictor ofpoor outcome in patients with
      thoracoabdominal injuries.

PMID- 29470901
TI  - [STRUCTURAL AND FUNCTIONAL PROPERTIES OF ERYTHROCYTES WHEN USING VARIOUS METHODS
      OF MULTICOMPONENT GENERAL ANESTHESIA AT LAPAROSCOPIC HOLETSISTEKTOMY AT PATIENTS
      WITH CHOLELITHIASIS.]
AB  - At patients with the verfied diagnosis have a cholelithiasis, transferred a
      laparoscopic holetsistektomy against the combined general anesthesia with muscle
      relaxants and artificial lung ventilation with use ofvarious anesthetics, the
      intraerythrocyte intensifi- cation of processes of peroxidation of lipids is
      established, and in a membrane of erythrocytes essential change of the contents
      and a ratio of the proteins and lipids responsible for structure, stabilization
      of a membrane and function of erythrocytes is revealed. Application of a
      sevoflurane, in comparison with propofol and, especially, a halothane, to a
      lesser extent influences structurally functional properties of erythrocytes that
      demands profile development ofpharmacological correction of the revealed
      violations.

PMID- 29470902
TI  - [AQUATIC AND ELECTROLYTE DISORDERS AT THE PATIENT WITH SEVERE TRAUMATIC BRAIN
      INJURY.]
AB  - This article is dedicated to the problem ofwater and electrolyte disturbances in
      patient with acute severe head trauma. We present the case study of patient with
      severe head injury who consistently developed diabetes insipidus and cerebral
      salt wasting syndrome. His water and electrolyte disorders were successfully
      corrected by target-oriented intensive care. Constant tight monitoring and of
      intensive care allowed to avoid secondary ischemic injuries till the water and
      electrolytic homeostasis regulation mechanisms restoration.

PMID- 29470903
TI  - [ANTIBACTERIAL THERAPY OF CATHETER ASSOCIATED URINARY TRACT INFECTION AFTER
      RADICAL PROSTATECTOMY.]
AB  - : Background Catheter associated urinary tract infections (CA UTI) are common
      nosocomial infections greatly increase morbidity and mortality and potentially
      increase hospital costs. Bladder catheterization is a common procedure, which
      surgical patients are undergone in the perioperative period, and the occurrence
      of about 80% of all urinary tract infections associated with it. There is no
      postoperative standard tactics of management patients with the urinary catheter.
      However, implementation of recommendations for the prevention of the development
      of CAUTI led to a reduction in the incidence of this type of hospital infections.
      Aim of our study is to analyse the incidence of catheter associated urinary tract
      infections in patients undergoing radical prostatectomy, and the establishment of
      indications for antibiotic therapy in the postoperative period, regarding to the
      riskfactors. METHODS: The 42 patients undergoing radical prostatectomy combined
      with pelvic lymphadenectomy were included into the study. The management of
      perioperative period and the antimicrobial policy was carried out according to
      the recommendations of IDSA 2009.

PMID- 29470904
TI  - [TO THE PROTOCOL OF ANTIBIOTIC PROPHYLAXIS IN CARDIAC SURGERY.]
AB  - BACKGROUND: Guidelines recommend that duration of antibiotic prophylaxis in
      cardiac surgery should be no more than 48 h, but at the same time it has been
      suggested that a 24h or even a single dose may be sufficient. THE AIM: To define
      whether 24-hour antibiotic prophylaxis on the incidence of infectious
      complications in cardiac surgery compared to the 72-hour period. Materials
      andmethods. All 125 patients were operatedfrom 01.01.2014 till 01.10.2014. All
      preoperative, intra and postoperative data were analyzed. Group 1 (n = 56) -
      these patients were administered cefazolinfor 24 h antibiotic prophylaxis (3
      g/day); group 2 (n = 69) -patients with cefazolin for 72 h antibiotic prophylaxis
      (1 g every 8 h). Pre and intraoperative characteristics were the same in both
      groups. RESULTS: Duration of stay in intensive care unit (ICU), postoperative
      hospitalization, sternomediastinitis frequency were also similar in both groups.
      The frequency of nosocomial pneumonia and rate ofprescription of antibiotics
      after antibiotic prophylaxis was significantly higher in group 1. CONCLUSION: 24
      hour antibiotic prophylaxis does not increase the frequency of the surgical
      field's infection, but the frequency of postoperative pneumonia and change of
      antibiotic prophylaxis on antibiotic therapy was higher in group 1.

PMID- 29470905
TI  - [ANAPHYLACTIC SHOCK AT 3,5 MONTH-LIFE CHILD (Case report).]
AB  - The article presents a clinical case of severe anaphylactic reaction to first
      introduced as complementary foods in the diet of the 3.5 months-life child
      formula based on cow milk.protein. Issues for discussion: the distribution of
      anaphylactic reactions in children, especially early age, causes, clinical
      features and the complex life-saving activities.

PMID- 29470906
TI  - [PROLONGED CARDIO-PULMONARY RESUSCITATION OF THE PATIENT WITH SEVERE ACCIDENTAL
      HYPOTHERMIA (clinical case).]
AB  - Cooling of the human body leads to progressive depression of cardiac activity,
      until it stops. In the presented clinical case is described of prolonged
      cardiopulmonary resuscitation (CPR) of a patient with accidental deep
      hypothermia. Also discuss the characteristics of CPR and the possible
      modification ofthe CPR algorithm in patients with severe hypothermia.

PMID- 29470907
TI  - [ADJUVANT ENERGY PROTECTION WITH REAMBERIN IN PRACTICE OF INTENSIVE CARE AND
      RESUSCITATION: META-ANALYSIS DATA ABOUT EFFECTIVENESS (SYSTEMATIC REVIEW).]
AB  - THE AIM: a synthesis of evaluations ofReamberin's clinical efficacy as energy
      protectorfor the results of a meta-analysis of published data obtained during
      controlled clinical studies with the same design and a high level of evidence.
      MATERIALS AND METHODS: To estimate succinic acid based remedy for infusions
      (reamberin), the meta-analysis was undertaken with data of reamberin use in
      intensive care, resuscitation departments, in critical post surgery period, in
      oncology (multiple chemotherapy of tumors), in emergent toxicology and
      pediatrics. 32 controlled randomized trials and all together 6221 patients were
      included. RESULTS: Unified indicators of clinical efficiency were systemically
      and thoroughly processed with advanced statistic tools, resulting data were
      sufficient for association and assessment of their heterogeneity in different
      articles. The adjuvant effects of reamberin were proven, as good outcome
      frequency enlarged more than by 25%, absolute and relative treatment benefits
      increased more than by 50%, positive outcome chance grew twice and more.
      CONCLUSIONS: According to sensitivity analysis and this meta-analysis results
      reamberin may be positioned as adjuvant energetic protector valid to improve
      effectiveness of pharmacologic correction during the treatment of emergencies
      joint with hypoxia, energy deficiencies and vegetative disregulations.

PMID- 29470908
TI  - Hexadecaphyrin-(1.0.0.0.1.1.0.1.1.0.0.0.1.1.0.1): A Dual Site Ligand That
      Supports Thermal Conformational Changes.
AB  - A new expanded porphyrin, hexadecaphyrin-(1.0.0.0.1.1.0.1.1.0.0.0.1.1.0.1), is
      reported. It was obtained via the condensation of a hexapyrrolic derivative
      prepared in turn from a bipyrrole dialdehyde and a stable quaterpyrrole
      precursor. This hexadecaphyrin contains eight direct alpha-pyrrole-to-alpha
      pyrrole linkages in its structure. It supports the formation of bimetallic
      complexes of both zinc and cobalt that are characterized by different
      conformational structures. Furthermore, a mixed zinc/cobalt macrocycle has been
      prepared. The cobalt bimetallic complex shows two stable conformations with the
      same oxidation state that are in equilibrium. All compounds have been
      characterized by common spectroscopic means, and single crystal X-ray diffraction
      structures were obtained for all macrocyclic compounds. DFT calculations and
      transient absorption spectra were used to study the electronic features of the
      complexes and the effect of conformational changes. This system shows promise as
      an accumulated heat sensor.

PMID- 29470909
TI  - Kernel Tuning and Nonuniform Influence on Optical and Electrochemical Gaps of
      Bimetal Nanoclusters.
AB  - Fine tuning nanoparticles with atomic precision is exciting and challenging and
      is critical for tuning the properties, understanding the structure-property
      correlation and determining the practical applications of nanoparticles. Some
      ultrasmall thiolated metal nanoparticles (metal nanoclusters) have been shown to
      be precisely doped, and even the protecting staple metal atom could be precisely
      reduced. However, the precise addition or reduction of the kernel atom while the
      other metal atoms in the nanocluster remain the same has not been successful
      until now, to the best of our knowledge. Here, by carefully selecting the
      protecting ligand with adequate steric hindrance, we synthesized a novel
      nanocluster in which the kernel can be regarded as that formed by the addition of
      two silver atoms to both ends of the Pt@Ag12 icosohedral kernel of the
      Ag24Pt(SR)18 (SR: thiolate) nanocluster, as revealed by single crystal X-ray
      crystallography. Interestingly, compared with the previously reported
      Ag24Pt(SR)18 nanocluster, the as-obtained novel bimetal nanocluster exhibits a
      similar absorption but a different electrochemical gap. One possible explanation
      for this result is that the kernel tuning does not essentially change the
      electronic structure, but obviously influences the charge on the Pt@Ag12 kernel,
      as demonstrated by natural population analysis, thus possibly resulting in the
      large electrochemical gap difference between the two nanoclusters. This work not
      only provides a novel strategy to tune metal nanoclusters but also reveals that
      the kernel change does not necessarily alter the optical and electrochemical gaps
      in a uniform manner, which has important implications for the structure-property
      correlation of nanoparticles.

PMID- 29470910
TI  - Fluctuation in Interface and Electronic Structure of Single-Molecule Junctions
      Investigated by Current versus Bias Voltage Characteristics.
AB  - Structural and electronic detail at the metal-molecule interface has a
      significant impact on the charge transport across the molecular junctions, but
      its precise understanding and control still remain elusive. On the single
      molecule scale, the metal-molecule interface structures and relevant charge
      transport properties are subject to fluctuation, which contain the fundamental
      science of single-molecule transport and implication for manipulability of the
      transport properties in electronic devices. Here, we present a comprehensive
      approach to investigate the fluctuation in the metal-molecule interface in single
      molecule junctions, based on current-voltage ( I- V) measurements in combination
      with first-principles simulation. Contrary to conventional molecular conductance
      studies, this I- V approach provides a correlated statistical description of both
      the degree of electronic coupling across the metal-molecule interface and the
      molecular orbital energy level. This statistical approach was employed to study
      fluctuation in single-molecule junctions of 1,4-butanediamine (DAB), pyrazine
      (PY), 4,4'-bipyridine (BPY), and fullerene (C60). We demonstrate that molecular
      dependent fluctuation of sigma-, pi-, and pi-plane-type interfaces can be
      captured by analyzing the molecular orbital (MO) energy level under mechanical
      perturbation. While the MO level of DAB with the sigma-type interface shows weak
      distance dependence and fluctuation, the MO level of PY, BPY, and C60 features
      unique distance dependence and molecular-dependent fluctuation against the
      mechanical perturbation. The MO level of PY and BPY with the sigma+pi-type
      interface increases with the increase in the stretch distance. In contrast, the
      MO level of C60 with the pi-plane-type interface decreases with the increase in
      the stretching perturbation. This study provides an approach to resolve the
      structural and electronic fluctuation in the single-molecule junctions and
      insight into the molecular-dependent fluctuation in the junctions.

PMID- 29470911
TI  - Comparison of Experimental and Broken Symmetry Density Functional Theory
      Calculated Electron Paramagnetic Resonance Parameters for the Manganese Catalase
      Active Site in the Superoxidized MnIII/MnIV State.
AB  - Broken symmetry density functional theory has been used to calculate g-tensor,
      55Mn, 14N, and 17O hyperfine couplings for active site models of superoxidized
      MnIII/MnIV manganese catalase both in its native and azide-inhibited form. While
      a good agreement is found between the calculated and experimental g-tensor and
      55Mn hyperfine couplings for all models, the active site geometry and Mn ion
      oxidation state can only be readily distinguished based on a comparison of the
      calculated and experimental 14N azide and 17O HFCs. This comparison shows that
      only models containing a Jahn-Teller distorted 5-coordinate (MnIII)2 site and a 6
      coordinate (MnIV)1 site can satisfactorily reproduce the experimental 14N and 17O
      hyperfine couplings.

PMID- 29470912
TI  - Halloysite Nanotubes-Induced Al Accumulation and Fibrotic Response in Lung of
      Mice after 30-Day Repeated Oral Administration.
AB  - Natural halloysite (Al2Si2O5(OH)4. nH2O) nanotubes (HNT) are clay materials with
      hollow tubular structure and are widely applied in many fields. Many in vitro
      studies indicate that HNTs exhibit a high level of biocompatibility; however, the
      in vivo toxicity of HNTs remains unclear. In this study, the biodistribution and
      pulmonary toxicity of the purified HNTs in mice were investigated after
      intragastric administration for 30 days. HNTs have high stability in biological
      conditions. Oral administration of HNTs caused significant Al accumulation
      predominantly in the lung with relative slight effects on Si biodistribution.
      Oral administration of HNTs stimulated the growth of the mice at low dose (5
      mg/kg BW) with no pulmonary toxicity but inhibited the mouse growth and resulted
      in oxidative stress and inflammation in lung at high dose (50 mg/kg BW). In
      addition, oral HNTs at high dose could be absorbed from the gastrointestinal
      tract and deposited in lung and could also induce pulmonary fibrosis.

PMID- 29470913
TI  - Interlocking Mechanism between Molecular Gears Attached to Surfaces.
AB  - While molecular machines play an increasingly significant role in nanoscience
      research and applications, there remains a shortage of investigations and
      understanding of the molecular gear (cogwheel), which is an indispensable and
      fundamental component to drive a larger correlated molecular machine system.
      Employing ab initio calculations, we investigate model systems consisting of
      molecules adsorbed on metal or graphene surfaces, ranging from very simple triple
      arm gears such as PF3 and NH3 to larger multiarm gears based on carbon rings. We
      explore in detail the transmission of slow rotational motion from one gear to the
      next by these relatively simple molecules, so as to isolate and reveal the
      mechanisms of the relevant intermolecular interactions. Several characteristics
      of molecular gears are discussed, in particular the flexibility of the arms and
      the slipping and skipping between interlocking arms of adjacent gears, which
      differ from familiar macroscopic rigid gears. The underlying theoretical concepts
      suggest strongly that other analogous structures may also exhibit similar
      behavior which may inspire future exploration in designing large correlated
      molecular machines.

PMID- 29470914
TI  - Stimuli-Responsive Multilayers Based on Thiolated Polysaccharides That Affect
      Fibroblast Cell Adhesion.
AB  - Control of the biomaterial properties through stimuli-responsive polymeric
      platforms has become an essential technique in recent biomedical applications. A
      multilayer system of thiolated chitosan (t-Chi) and thiolated chondroitin sulfate
      (t-CS), consisting of five double layers ([t-Chi/t-CS]5), was fabricated here by
      applying a layer-by-layer coating strategy. To represent a novel class of
      chemically tunable nanostructures, the ability to cross-link pendant thiol groups
      was tested by a rise from pH 4 during layer formation to pH 9.3 and a more
      powerful chemical stimulus by using chloramine-T (ChT). Following both
      treatments, the resulting multilayers showed stimuli-dependent behavior, as
      demonstrated by their content of free thiols, wettability, surface charge,
      elastic modulus, roughness, topography, thickness, and binding of fibronectin.
      Studies with human dermal fibroblasts further demonstrated the favorable
      potential of the ChT-responsive multilayers as a cell-adhesive surface compared
      to pH-induced cross-linking. Because the [t-Chi/t-CS]5 multilayer system is
      responsive to stimuli such as the pH and redox environment, multilayer systems
      with disulfide bond formation may help to tailor their interaction with cells,
      film degradation, and controlled release of bioactive substances like growth
      factors in a stimuli-responsive manner useful in future wound healing and tissue
      engineering applications.

PMID- 29470915
TI  - Magnetically Modified Agricultural and Food Waste: Preparation and Application.
AB  - The annual food and agricultural waste production reaches enormous numbers.
      Therefore, an increasing need to valorize produced wastes arises. Waste materials
      originating from the food and agricultural industry can be considered as
      functional materials with interesting properties and broad application potential.
      Moreover, using an appropriate magnetic modification, smart materials exhibiting
      a rapid response to an external magnetic field can be obtained. Such materials
      can be easily and selectively separated from desired environments. Magnetically
      responsive waste derivatives of biological origins have already been prepared and
      used as efficient biosorbents for the isolation and removal of both biologically
      active compounds and organic and inorganic pollutants and radionuclides, as
      biocompatible carriers for the immobilization of diverse types of (bio)molecules,
      cells, nano- and microparticles, or (bio)catalysts. Potential bactericidal,
      algicidal, or anti-biofilm properties of magnetic waste composites have also been
      tested. Furthermore, low cost and availability of waste biomaterials in larger
      amounts predetermine their utilization in large-scale processes.

PMID- 29470916
TI  - Micromotors for "Chemistry-on-the-Fly".
AB  - This perspective reviews mobile micro/nanomotor scaffolds for performing
      "chemistry-on-the-fly". Synthetic nano/micromotors offer great versatility and
      distinct advantages in diverse chemical applications owing to their efficient
      propulsion and facile surface functionalization that allow these mobile platforms
      to move and disperse reactive materials across the solution. Such dynamic
      microreactors have led to accelerated chemical processes, including organic
      pollutant degradation, metal chelation, biorecognition, redox chemistry, chemical
      "writing", and a variety of other chemical transformations. Representative
      examples of such micromotor-enhanced chemical reactions are discussed, focusing
      on the specific chemical role of these mobile microreactors. The advantages, gaps
      and limitations of using micromotors as mobile chemical platforms are discussed,
      concluding with the future prospects of this emerging field. We envision that
      artificial nano/micromotors will become attractive dynamic tools for speeding up
      and enhancing "on-the-fly" chemical reactions.

PMID- 29470917
TI  - Theoretical Studies on the Photophysics and Photochemistry of 5-Formylcytosine
      and 5-Carboxylcytosine: The Oxidative Products of Epigenetic Modification of
      Cytosine in DNA.
AB  - Cytosine methylation and demethylation play crucial roles in understanding the
      genomic DNA expression regulation. The epigenetic modification of cytosine and
      its continuous oxidative products are called the "new four bases of DNA"
      including 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5
      formylcytosine (5fC), and 5-carboxylcytosine (5caC). However, compared to the
      abundant studies on the classical DNA bases, the photophysical and photochemical
      properties of those new bases have not yet aroused people's excessive attention.
      In this contribution, a systematic study on the nonradiative decay and
      photochemical pathways via excited states or conical intersections upon
      photoexcitation has been explored through high-level computational approaches
      such as the complete active space self-consistent field method, complete active
      space with second-order perturbation theory, and density functional theory.
      Pathways like the ring-distortion deactivation, hydrogen dissociation, hydrogen
      transfer, and also Norrish type I and II photochemical reactions have been
      investigated, and it was proposed that intersystem crossing from the S1 state to
      the T1 state is the most effective route for 5fC. For 5caC, ring-pucking and
      intramolecular isomerism are effective deactivation ways at both neutral and
      protonated forms. In the meantime, the influences of two important environmental
      factors, the solution and acidic environment (i.e., the protonated state), were
      also considered in this study. From the theoretical perspective, the initial
      properties of the photostability and photochemical reactivity for 5fC and 5caC
      have become a crucial aspect to facilitate a further comprehension of their
      potential role in gene regulation and transcription.

PMID- 29470918
TI  - Early Immune Function and Duration of Organ Dysfunction in Critically III
      Children with Sepsis.
AB  - RATIONALE: Late immune suppression is associated with nosocomial infection and
      mortality in adults and children with sepsis. Relationships between early immune
      suppression and outcomes in children with sepsis remain unclear. OBJECTIVES:
      Prospective observational study to test the hypothesis that early innate and
      adaptive immune suppression are associated with longer duration of organ
      dysfunction in children with severe sepsis or septic shock. METHODS: Children
      younger than 18 years of age meeting consensus criteria for severe sepsis or
      septic shock were sampled within 48 hours of sepsis onset. Healthy control
      subjects were sampled once. Innate immune function was quantified by whole blood
      ex vivo LPS-induced TNF-alpha (tumor necrosis factor-alpha) production capacity.
      Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFN
      gamma production capacity. MEASUREMENTS AND MAIN RESULTS: One hundred two
      children with sepsis and 35 healthy children were enrolled. Compared with healthy
      children, children with sepsis demonstrated lower LPS-induced TNF-alpha
      production (P < 0.0001) and lower phytohemagglutinin-induced IFN-gamma production
      (P < 0.0001). Among children with sepsis, early innate and adaptive immune
      suppression were associated with greater number of days with multiple organ
      dysfunction syndrome and greater number of days with any organ dysfunction. On
      multivariable analyses, early innate immune suppression remained independently
      associated with increased multiple organ dysfunction syndrome days (adjusted
      relative risk, 1.2; 95% confidence interval, 1.03-1.5) and organ dysfunction days
      (adjusted relative risk, 1.2; 95% confidence interval, 1.1-1.3). CONCLUSIONS:
      Critically ill children with severe sepsis or septic shock demonstrate early
      innate and adaptive immune suppression. Early innate and adaptive immune
      suppression are associated with longer durations of organ dysfunction and may be
      useful markers to help guide future investigations of immunomodulatory therapies
      in children with sepsis.

PMID- 29470920
TI  - Long-Term Microevolution of Pseudomonas aeruginosa Differs between Mildly and
      Severely Affected Cystic Fibrosis Lungs.
AB  - Chronic airway infections with Pseudomonas aeruginosa determine morbidity in most
      individuals with cystic fibrosis (CF). P. aeruginosa may persist for decades in
      CF lungs, which provides a rare opportunity to study the long-term within-host
      evolution of a bacterial airway pathogen. In this work, we sought to resolve the
      genetic adaptation of P. aeruginosa in CF lungs from the onset of colonization
      until the patient's death or permanent replacement by another P. aeruginosa
      clone. We followed the microevolution of the first persisting P. aeruginosa clone
      by whole-genome sequencing of serial isolates from highly divergent clinical
      courses of airway infection, i.e., a fatal outcome because of respiratory
      insufficiency within less than 15 years, or a rather normal daily life 25-35
      years after acquisition of P. aeruginosa. Nonneutral mutations predominantly
      emerged in P. aeruginosa genes relevant for protection against and communication
      with signals from the lung environment, i.e., antibiotic resistance, cell wall
      components, and two-component systems. Drastic and loss-of-function mutations
      preferentially happened during the severe courses of infection, and the bacterial
      lineages of the mild courses more proficiently incorporated extra metabolic genes
      into their accessory genome. P. aeruginosa followed different evolutionary paths
      depending on whether the bacterium had taken up residence in a patient with CF
      and normal or already compromised lung function.

PMID- 29470928
TI  - Longitudinal Assessment of Lung Function in Survivors of Bronchopulmonary
      Dysplasia from Birth to Adulthood. The Padova BPD Study.

PMID- 29470929
TI  - Interferon Alpha-2a for the Treatment of Post-Infectious Uveitis Secondary to
      Presumed Intraocular Tuberculosis.
AB  - PURPOSE: To assess the efficacy and tolerability of interferon (IFN) alpha-2a in
      post-infectious uveitis secondary to presumed intraocular tuberculosis (IOTB).
      METHODS: Patients with chronic uveitis secondary to presumed IOTB who, after
      completing an antitubercular treatment, showed poor response to treatments or
      recurred after tapering oral corticosteroids to <=7.5 mg/day were enrolled. All
      patients were treated with IFN alpha-2a subcutaneous injections. Best-corrected
      visual acuity (BCVA), central retinal thickness (CRT), and inflammatory signs
      were compared between baseline and follow-up visits up to six months. RESULTS:
      Twelve eyes (six patients) were enrolled. Mean BCVA improved from 0.64 +/- 0.55
      logMAR at baseline to 0.32 +/- 0.31 logMAR at 6 months (p = 0.03). Mean CRT
      decreased from 372 +/- 132.2 MUm to 274.66 +/- 34.9 MUm at six months (p = 0.01).
      Inflammatory signs (vitritis, vasculitis) also decreased overtime. No major
      complications or tuberculosis reactivations were recorded. CONCLUSIONS: IFN alpha
      2a was efficacious and safe in treating chronic post-infectious uveitis secondary
      to presumed IOTB.

PMID- 29470930
TI  - Diagnostic Utility of Quantitative Polymerase Chain Reaction versus Culture in
      Endophthalmitis and Uveitis.
AB  - PURPOSE: To compare genetic testing for microbes in infectious endophthalmitis or
      uveitis to culture. METHODS: This was a retrospective, single-center case series
      that enrolled patients with clinically suspected endophthalmitis or uveitis of
      unknown etiology. Aqueous humor or vitreous was collected and sent for routine
      cultures and genetic testing. RESULTS: In total, 46 patients were enrolled.
      Genetic testing was positive in 32/46 (70%) cases and culture 6/46 cases (13%).
      Five of 16 uveitis cases had a final clinical diagnosis of infectious uveitis,
      and polymerase chain reaction (PCR) was positive in 4/5 cases (80%), versus 0%
      for culture. In uveitis cases, PCR was 80% sensitive and 82% specific, and
      culture had 0% sensitivity. The overall sensitivity and specificity of PCR for
      all cases were 85% and 67%, respectively, compared with 17% and 100% for culture.
      CONCLUSION: Genetic assays are inexpensive ($25/case) and more sensitive than
      culture for identifying intraocular pathogens in endophthalmitis and uveitis.

PMID- 29470931
TI  - The need for sustainability and alignment of future support for National
      Immunization Technical Advisory Groups (NITAGs) in low and middle-income
      countries.
AB  - National Immunisation Technical Advisory Groups (NITAGs) provide independent
      guidance to health ministries to support evidence-based and nationally relevant
      immunisation decisions. We examined NITAGs' value, sustainability, and need for
      support in low and middle-income countries, drawing from a mixed-methods study
      including 130 global and national-level key informant interviews. NITAGs were
      particularly valued for providing independent and nationally owned evidence-based
      decision-making (EBDM), but needed to be integrated within national processes to
      effectively balance independence and influence. Participants agreed that most
      NITAGs, being relatively new, would need developmental and strengthening support
      for at least a decade. While national governments could support NITAG
      functioning, external support is likely needed for requisite capacity building.
      This might come from Gavi mechanisms and WHO, but would require alignment among
      stakeholders to be effective.

PMID- 29470932
TI  - Precise identification of wheat - Thinopyrum intermedium translocation
      chromosomes carrying resistance to wheat stripe rust in line Z4 and its derived
      progenies.
AB  - The wheat - Thinopyrum intermedium derived line Z4 has displayed novel and
      effective stripe rust resistance for over 40 years. This study aimed to precisely
      identify the chromosome constitution of line Z4 and determine the stripe rust
      resistance contribution using multicolor fluorescent in situ hybridization (FISH)
      and molecular marker analysis. The results indicated that the Z4 line (2n = 44)
      contained two pairs of non-Robertsonian translocations without the 3A chromosomes
      of wheat. FISH karyotypes of F3 progenies derived from crosses between Z4 and
      MY11 indicated that the transmission of the translocated chromosomes appeared
      normal and the number of wheat chromosomes 3A and 3D frequently varied. The FISH
      signal distribution of a new repetitive probe, named Oligo-3A1, confirmed the
      physical breakage points on chromosome 3AL incorporated into translocated
      chromosomes. PLUG markers revealed the breakage points on chromosomes 3A, 7JS,
      and 3D invloved in the translocated chromosomes, and they were designated as T3DS
      3AS.3AL-7JSS and T3AL-7JSS.7JSL. Stripe rust resistances surveys indicated that
      the proximal region of 7JSS or 7JSL may confer the resistance at the adult plant
      stage. The precise characterization of the chromosome complements of wheat - Th.
      intermedium Z4 and derived progenies has demonstrated the importance of combining
      cytogenetic and molecular approaches in the genomics era for further wheat
      genetic manipulation and breeding purposes.

PMID- 29470933
TI  - Fluorescein Labeled Leukocytes for in vivo Imaging of Retinal Vascular
      Inflammation and Infiltrating Leukocytes in Laser-Induced Choroidal
      Neovascularization Model.
AB  - PURPOSE: To study the effect of anti-VEGF treatment on retinal inflammation in a
      laser-induced CNV rodent model. METHODS: Leukocytes labeled with 1% sodium
      fluorescein were injected into the laser-induced CNV (wild type C57BL/6) mice at
      days 4 (baseline), 7, 14, and 19. At baseline intravitreally 3 mice received 1*
      PBS, and 3 mice received anti-VEGF. FFA, OCT, and SLO were performed at each time
      point to assess the CNV pathophysiology and inflammatory response. RESULTS:
      Fluorescein leakage, SRF, and leukocyte infiltration were observed at baseline in
      both the groups before injection. From days 7 to 19, leukocyte infiltration and
      SRF were noted in the 1* PBS group, but limited or no SRF and leukocyte
      infiltration was observed in the anti-VEGF group. CONCLUSIONS: Leukocyte
      infiltration was established as an in vivo imaging inflammatory marker and along
      with FFA and OCT showed response to anti-VEGF therapy in laser-induced CNV model.

PMID- 29470934
TI  - Bivalent oral cholera vaccine in participants aged 1 year and older in the
      Dominican Republic: A phase III, single-arm, safety and immunogenicity trial.
AB  - The Dominican Republic, historically non-endemic for cholera, is experiencing an
      ongoing cholera epidemic. We assessed the safety and immunogenicity of two doses
      of the killed bivalent (O1 and O139) whole-cell oral cholera vaccine (OCV) on day
      (D)0 and D14 in healthy participants aged >=1 year. Immediate unsolicited
      systemic adverse events (AEs) were monitored up to 30 minutes and solicited
      systemic reactions, up to 7 days after each vaccination. Unsolicited AEs were
      recorded up to D14 (post-dose 1) and 30 days post-dose 2. A vibriocidal antibody
      assay with microtiter technique was used to measure serum antibodies to V.
      cholerae strains (O1 El Tor Inaba, O1 El Tor Ogawa, O139) on D0, D14 and D28.
      Geometric mean titers (GMTs) and seroconversion (>=4-fold increase from D0) rates
      were calculated. We recruited 336 participants; 112 in three age groups (1-4, 5
      14 and >=15 years). No safety concerns were observed. GMTs increased from
      baseline for all serotypes, with marked increases for O1 Inaba and Ogawa post
      dose 1. Post-dose 2 GMTs tended to be equal or slightly lower, with ranges: O1
      Inaba, 283 (95% confidence interval 191-419) to 612 (426-880); O1 Ogawa, 346 (223
      536) to 754 (553-1028); and O139, 20.3 (13.5-30.6) to 43.8 (30.1-63.7).
      Seroconversion rates post-dose 2 for O1 Inaba and Ogawa were high (>=87%) for all
      age groups. OCV demonstrated an acceptable safety profile and robust
      immunogenicity in these participants, in-line with previous observations in
      epidemic and endemic settings.This study is registered on www.clinicaltrials.gov
      (NCT02434822).

PMID- 29470937
TI  - Renal Lesion Characterization with Spectral CT: Determining the Optimal Energy
      for Virtual Monoenergetic Reconstruction.
AB  - Purpose To investigate the relationship between energy level of virtual
      monoenergetic (VM) imaging and sensitivity in the detection of minimally
      enhancing renal lesions. Materials and Methods Phantoms simulating unenhanced and
      contrast material-enhanced renal parenchyma were equipped with inserts containing
      different concentrations of iodine (range, 0-1.15 mg iodine per milliliter). A
      total of 180 patients (117 men; mean age, 65.2 years +/- 13.0 [standard
      deviation]) with 194 (62 solid, 132 cystic) renal lesions larger than 10 mm in
      diameter underwent unenhanced single-energy CT and contrast-enhanced dual-energy
      CT. VM imaging data sets were created for 70, 80, 90, and 100 keV. Renal lesions
      were measured, and enhancement was calculated. Area under the receiver operating
      characteristic curve (AUC) for renal lesion characterization was determined by
      using the DeLong method. Results The AUC was highest at 70 keV and decreased as
      energy increased toward 100 keV. AUC in the phantom decreased from 98% (95%
      confidence interval [CI]: 95, 100) at 70 keV to 88% (95% CI: 79, 96) at 100 keV
      (P = .004). AUC in patients decreased from 96% (95% CI: 94, 98) at 70 keV to 79%
      (95% CI: 71, 86) at 100 keV (P = .001). In patients with an enhancement threshold
      of 15 HU, sensitivity in the detection of solid renal lesions decreased between
      from 91% (49 of 62 [95% CI: 78, 97]) at 70 keV to 48% (33 of 62 [95% CI: 25, 71])
      at 100 keV (P < .05), with no change in specificity (93% [120 of 132 {95% CI: 87,
      97}] at 70 keV, 97% [125 of 132 {95% CI: 92, 99}] at 100 keV). Conclusion There
      is a reduction in diagnostic accuracy for renal lesion characterization with
      increasing VM imaging energy. The 70-keV setting may provide an optimal trade-off
      between sensitivity and specificity. (c) RSNA, 2018 Online supplemental material
      is available for this article.

PMID- 29470938
TI  - Diagnostic Performance of MR Elastography for Liver Fibrosis in Children and
      Young Adults with a Spectrum of Liver Diseases.
AB  - Purpose To assess the diagnostic performance of magnetic resonance (MR)
      elastography-derived liver stiffness to detect liver fibrosis in a pediatric and
      young adult population with a spectrum of liver diseases. Materials and Methods
      This retrospective study included patients younger than 21 years of age who
      underwent MR elastography and liver biopsy within 3 months of one another between
      January 2012 and September 2016 for indications other than liver transplantation
      or Fontan palliation of congenital heart disease. MR elastography examinations
      were reprocessed by a single observer, blinded to pathologic findings. Pathology
      specimens were reviewed by a single pathologist who scored steatosis (lipid in >=
      5% of hepatocytes) and staged fibrosis. Receiver operating characteristic (ROC)
      curves were used to assess diagnostic performance. Results A total of 86
      patients, 49 (57%) male with a median age of 14.2 years (range, 0.3-20.6 years),
      were included. Fifty-one patients (59.3%) had Ludwig stage 2 or higher fibrosis;
      44 patients (51.2%) had hepatic steatosis. The area under the ROC curve for
      Ludwig stage 0-1 versus stage 2 or higher fibrosis was 0.70 (95% confidence
      interval [CI]: 0.59, 0.81) for the whole population and was significantly lower
      for patients with steatosis versus those without (0.53 [95% CI: 0.35, 0.71] vs
      0.82 [95% CI: 0.67, 0.96], P = .014). Optimal stiffness cut-offs for the entire
      population were 2.27 kPa with 68.6% sensitivity (95% CI: 57.2%, 80.1%) and 74.3%
      specificity (95% CI: 63.5%, 85.1%) or 1.67 kPa with 35.3% sensitivity (95% CI:
      23.5%, 47.1%) and 91.4% specificity (95% CI: 84.5%, 98.3%). Conclusion In
      children and young adults, MR elastography performs significantly better for
      distinguishing stage 0-1 versus stage 2 or higher fibrosis in patients without
      steatosis than in those with steatosis. This suggests a confounding effect of
      steatosis or inflammation in the population with nonalcoholic fatty liver
      disease. (c) RSNA, 2018.

PMID- 29470939
TI  - Free-breathing Pulmonary MR Imaging to Quantify Regional Ventilation.
AB  - Purpose To measure regional specific ventilation with free-breathing hydrogen 1
      (1H) magnetic resonance (MR) imaging without exogenous contrast material and to
      investigate correlations with hyperpolarized helium 3 (3He) MR imaging and
      pulmonary function test measurements in healthy volunteers and patients with
      asthma. Materials and Methods Subjects underwent free-breathing 1H and static
      breath-hold hyperpolarized 3He MR imaging as well as spirometry and
      plethysmography; participants were consecutively recruited between January and
      June 2017. Free-breathing 1H MR imaging was performed with an optimized balanced
      steady-state free-precession sequence; images were retrospectively grouped into
      tidal inspiration or tidal expiration volumes with exponentially weighted phase
      interpolation. MR imaging volumes were coregistered by using optical flow
      deformable registration to generate 1H MR imaging-derived specific ventilation
      maps. Hyperpolarized 3He MR imaging- and 1H MR imaging-derived specific
      ventilation maps were coregistered to quantify regional specific ventilation
      within hyperpolarized 3He MR imaging ventilation masks. Differences between
      groups were determined with the Mann-Whitney test and relationships were
      determined with Spearman (rho) correlation coefficients. Statistical analyses
      were performed with software. Results Thirty subjects (median age: 50 years;
      interquartile range [IQR]: 30 years), including 23 with asthma and seven healthy
      volunteers, were evaluated. Both 1H MR imaging-derived specific ventilation and
      hyperpolarized 3He MR imaging-derived ventilation percentage were significantly
      greater in healthy volunteers than in patients with asthma (specific ventilation:
      0.14 [IQR: 0.05] vs 0.08 [IQR: 0.06], respectively, P < .0001; ventilation
      percentage: 99% [IQR: 1%] vs 94% [IQR: 5%], P < .0001). For all subjects, 1H MR
      imaging-derived specific ventilation correlated with plethysmography-derived
      specific ventilation (rho = 0.54, P = .002) and hyperpolarized 3He MR imaging
      derived ventilation percentage (rho = 0.67, P < .0001) as well as with forced
      expiratory volume in 1 second (FEV1) (rho = 0.65, P = .0001), ratio of FEV1 to
      forced vital capacity (rho = 0.75, P < .0001), ratio of residual volume to total
      lung capacity (rho = -0.68, P < .0001), and airway resistance (rho = -0.51, P =
      .004). 1H MR imaging-derived specific ventilation was significantly greater in
      the gravitational-dependent versus nondependent lung in healthy subjects (P =
      .02) but not in patients with asthma (P = .1). In patients with asthma,
      coregistered 1H MR imaging specific ventilation and hyperpolarized 3He MR imaging
      maps showed that specific ventilation was diminished in corresponding 3He MR
      imaging ventilation defects (0.05 +/- 0.04) compared with well-ventilated regions
      (0.09 +/- 0.05) (P < .0001). Conclusion 1H MR imaging-derived specific
      ventilation correlated with plethysmography-derived specific ventilation and
      ventilation defects seen by using hyperpolarized 3He MR imaging. (c) RSNA, 2018
      Online supplemental material is available for this article.

PMID- 29470944
TI  - Antimicrobial resistance and prevalence of diarrheagenic Escherichia coli (DEC),
      in diarrheic yaks of Tibetan Plateau, China.
AB  - This study was conducted to test the distribution of diarrheagenic Escherichia
      coli (DEC) associated genes in fecal isolates from diarrheic yaks of a high
      remote region of China. Briefly, we obtained 203 fecal samples from diarrheic
      adult yaks and E. coli strains were isolated and identified via standard methods
      The antibiotic sensitivity of isolates was determined via disk diffusion method
      and polymerase chain reaction (PCR) was used to detect the DEC virulence
      associated genes. Results of the current study showed a high rate of resistance
      to tetracycline (93.6%) and low rate of resistance to ofloxacin (16.7%)
      antibiotics. Meanwhile, five different diarrheagenic associated virulence traits
      were detected including; EAEC (11.80%), EHEC (25.62%), EIEC (17.18%), EPEC
      (36.92%) and ETEC (11.36%). Moreover, E. coli isolates were positive for all
      tested DEC associated virulence genes ranging from 1.48% to 33%. Additionally,
      four isolates were positive for more than one virulence genes. In conclusion, our
      investigation showed a relatively low number of E. coli virulence genes isolated
      from diarrheic Tibetan yaks, which could be attributed to the high altitude
      induced harsh environmental conditions that may not help in the growth and
      survival of pathogenic organisms. In addition, this study highlights the high
      level of antibiotic resistance in yaks, therefore; preventive measures should be
      taken to monitor the antibiotic usage in Tibet region of China.

PMID- 29470945
TI  - Porcine circovirus 2 in the North Eastern region of India: Disease prevalence and
      genetic variation among the isolates from areas of intensive pig rearing.
AB  - Porcine Circovirus type-2 (PCV-2) is considered as a major threat to the piggery
      sector in India. To ascertain the epidemiological status and infection level of
      PCV2, a pilot study was undertaken to find out the prevalence of PCV2 in swine
      population by ELISA and PCR in the interior and border areas of Meghalaya which
      includes the area where accessibility and medical aid is a rare phenomenon. A
      total of 249 serum samples were collected from October 2014 to February 2016 from
      three divisions of Meghalaya: Khasi, Jaintia and Garo Hills Divisions. The mean
      positivity of PCV-2 antibodies in suspected sera was 83.93% whereas 62.25% of the
      suspected samples respectively were found to contain PCV2 as detected by PCR.
      Additional 190 tissue samples were collected during necropsy from both
      symptomatic and asymptomatic animals following reported outbreak in this region,
      which indicated a mean positivity of 18.94% (36/190); out of which 13 samples
      were subjected to sequencing to find out the genetic diversity of PCV2 amongst
      the field isolates. Molecular characterization and phylogenetic analysis of PCV2
      isolates based on cap gene depicted genetic diversity among the strains in pig
      population of Meghalaya as the isolates belonged to PCV2a, PCV2b-1c and PCV2d
      genotypes; identification of the PCV2d genotype is probably the first report from
      Meghalaya. Four isolates forming an outlier group in the phylogenetic tree were
      arising out of natural inter-genotypic recombination between PCV2a and PCV2b.
      PCV2 being immunosuppressive in nature impairs the host immune response
      increasing the susceptibility to other co-infections leading to disease severity
      and high mortality in pig population. This baseline data gives a brief
      epidemiological status of PCV2 infection and circulating PCV2 genotype in this
      region which will be useful in the formulation of control and eradication
      programs in remotes areas of Meghalaya where accessibility is less and
      vaccination is a rare practice.

PMID- 29470946
TI  - Effect of ubiquinone-10 on the stability of biomimetic membranes of relevance for
      the inner mitochondrial membrane.
AB  - Ubiquinone-10 (Q10) plays a pivotal role as electron-carrier in the mitochondrial
      respiratory chain, and is also well known for its powerful antioxidant
      properties. Recent findings suggest moreover that Q10 could have an important
      membrane stabilizing function. In line with this, we showed in a previous study
      that Q10 decreases the permeability to carboxyfluorescein (CF) and increases the
      mechanical strength of 1-palmitoyl-2-oleyl-sn-glycero-phosphocholine (POPC)
      membranes. In the current study we report on the effects exerted by Q10 in
      membranes having a more complex lipid composition designed to mimic that of the
      inner mitochondrial membrane (IMM). Results from DPH fluorescence anisotropy and
      permeability measurements, as well as investigations probing the interaction of
      liposomes with silica surfaces, corroborate a membrane stabilizing effect of Q10
      also in the IMM-mimicking membranes. Comparative investigations examining the
      effect of Q10 and the polyisoprenoid alcohol solanesol on the IMM model and on
      membranes composed of individual IMM components suggest, moreover, that Q10
      improves the membrane barrier properties via different mechanisms depending on
      the lipid composition of the membrane. Thus, whereas Q10's inhibitory effect on
      CF release from pure POPC membranes appears to be directly and solely related to
      Q10's lipid ordering and condensing effect, a mechanism linked to Q10's ability
      to amplify intrinsic curvature elastic stress dominates in case of membranes
      containing high proportions of palmitoyl-2-oleoyl-sn-glycero-3
      phosphoethanolamine (POPE).

PMID- 29470947
TI  - Small and large intestine express a truncated Dab1 isoform that assembles in cell
      cell junctions and co-localizes with proteins involved in endocytosis.
AB  - Disabled-1 (Dab1) is an essential intracellular adaptor protein in the reelin
      pathway. Our previous studies in mice intestine showed that Dab1 transmits the
      reelin signal to cytosolic signalling pathways. Here, we determine the Dab1
      isoform expressed in rodent small and large intestine, its subcellular location
      and co-localization with clathrin, caveolin-1 and N-Wasp. PCR and sequencing
      analysis reveal that rodent small and large intestine express a Dab1 isoform that
      misses three (Y198, Y200 and Y220) of the five tyrosine phosphorylation sites
      present in brain Dab1 isoform (canonical) and contains nuclear localization and
      export signals. Western blot assays show that both, crypts, which shelter
      progenitor cells, and enterocytes express the same Dab1 isoform, suggesting that
      epithelial cell differentiation does not regulate intestinal generation of
      alternatively spliced Dab1 variants. They also reveal that the canonical and the
      intestinal Dab1 isoforms differ in their total degree of phosphorylation.
      Immunostaining assays show that in enterocytes Dab1 localizes at the apical and
      lateral membranes, apical vesicles, close to adherens junctions and desmosomes,
      as well as in the nucleus; co-localizes with clathrin and with N-Wasp but not
      with caveolin-1, and in Caco-2 cells Dab1 localizes at cell-to-cell junctions by
      a Ca2+-dependent process. In conclusion, the results indicate that in rodent
      intestine a truncated Dab1 variant transmits the reelin signal and may play a
      role in clathrin-mediated apical endocytosis and in the control of cell-to-cell
      junction assembly. A function of intestinal Dab1 variant as a nucleocytoplasmic
      shuttling protein is also inferred from its sequence and nuclear location.

PMID- 29470948
TI  - Direct analysis of PI(3,4,5)P3 using liquid chromatography electrospray
      ionization tandem mass spectrometry.
AB  - Phosphatidylinositol (3,4,5) trisphosphate (PIP3) is a biologically active
      membrane phospholipid that is essential for the growth and survival of all
      eukaryotic cells. We describe a new method that directly measures PIP3 and
      describe the HPLC separation and measurement of the positional isomers of
      phosphatidylinositol bisphosphate, PI(3,5)P2, PI(3,4)P2 and PI(4,5)P2. Mass
      spectrometric analyses were performed online using ultra-high performance liquid
      chromatography (UHPLC)-electrospray ionization tandem mass spectrometry (LC-ESI
      MS/MS) in the negative multiple-reaction monitoring (MRM) modes. Rapid separation
      of PIP3 from PI, phosphatidylinositol phosphate (PIP) and PIP2 was accomplished
      by C18 reverse phase chromatography with the addition of the ion pairing reagents
      diisopropylethanolamine (DiiPEA) and ethylenediamine tetraacetic acid tetrasodium
      salt dihydrate (EDTA) to the samples and mobile phase with a total run time,
      including equilibration, of 12 min. Importantly, these chromatography conditions
      result in no carryover of PIP, PIP2, and PIP3 between samples. To validate the
      new method, U87MG cancer cells were serum starved and treated with PDGF to
      stimulate PIP3 biosynthesis in the presence or absence of the
      phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Results generated with
      the LC/MS method were in excellent agreement with results generated using [33P]
      phosphate radiolabeled U87MG cells and anion exchange chromatography analysis, a
      well validated method for measuring PIP3. To demonstrate the usefulness of the
      new method, we generated reproducible IC50 data for several well-characterized
      PI3K small molecule inhibitors using a U87MG cell-based assay as well as showing
      PIP3 can be measured from additional cancer cell lines. Together, our results
      demonstrate this novel method is sensitive, reproducible and can be used to
      directly measure PIP3 without radiolabeling or complex lipid derivatization.

PMID- 29470949
TI  - Amputation of a C-terminal helix of the gamma subunit increases ATP-hydrolysis
      activity of cyanobacterial F1 ATP synthase.
AB  - F1 is a soluble part of FoF1-ATP synthase and performs a catalytic process of ATP
      hydrolysis and synthesis. The gamma subunit, which is the rotary shaft of F1
      motor, is composed of N-terminal and C-terminal helices domains, and a protruding
      Rossman-fold domain located between the two major helices parts. The N-terminal
      and C-terminal helices domains of gamma assemble into an antiparallel coiled-coil
      structure, and are almost embedded into the stator ring composed of alpha3beta3
      hexamer of the F1 molecule. Cyanobacterial and chloroplast gamma subunits harbor
      an inserted sequence of 30 or 39 amino acids length within the Rossman-fold
      domain in comparison with bacterial or mitochondrial gamma. To understand the
      structure-function relationship of the gamma subunit, we prepared a mutant F1-ATP
      synthase of a thermophilic cyanobacterium, Thermosynechococcus elongatus BP-1, in
      which the gamma subunit is split into N-terminal alpha-helix along with the
      inserted sequence and the remaining C-terminal part. The obtained mutant showed
      higher ATP-hydrolysis activities than those containing the wild-type gamma.
      Contrary to our expectation, the complexes containing the split gamma subunits
      were mostly devoid of the C-terminal helix. We further investigated the effect of
      post-assembly cleavage of the gamma subunit. We demonstrate that insertion of the
      nick between two helices of the gamma subunit imparts resistance to ADP
      inhibition, and the C-terminal alpha-helix is dispensable for ATP-hydrolysis
      activity and plays a crucial role in the assembly of F1-ATP synthase.

PMID- 29470950
TI  - Not seeking yet trying long-acting reversible contraception: a 24-month
      randomized trial on continuation, unintended pregnancy and satisfaction.
AB  - OBJECTIVES: To measure the 24-month impact on continuation, unintended pregnancy
      and satisfaction of trying long-acting reversible contraception (LARC) in a
      population seeking short-acting reversible contraception (SARC). STUDY DESIGN: We
      enrolled 916 women aged 18-29 who were seeking pills or injectables in a
      partially randomized patient preference trial. Women with strong preferences for
      pills or injectables started on those products, while others opted for
      randomization to LARC or SARC and received their methods gratis. We estimated
      continuation and unintended pregnancy rates through 24months. Intent-to-treat
      principles were applied after method initiation for comparing incidence of
      unintended pregnancy. We also examined how satisfaction levels varied by cohort
      and how baseline negative LARC attitudes were associated with satisfaction over
      time. RESULTS: Forty-three percent chose randomization, and 57% chose the
      preference option. Complete loss to follow-up was<2%. The 24-month LARC
      continuation probability was 64.3% [95% confidence interval (CI): 56.6-70.9],
      statistically higher than SARC groups [25.5% (randomized) and 40.0%
      (preference)]. The 24-month cumulative unintended pregnancy probabilities were
      9.9% (95% CI: 7.2-12.6) (preference-SARC), 6.9% (95% CI: 3.3-10.6) (randomized
      SARC) and 3.6% (95% CI: 1.8-6.4) (randomized-LARC). Statistical tests for
      comparing randomized groups on unintended pregnancy were mixed: binomial at 24
      month time point (p=.02) and log-rank survival probabilities (p=.14 for first
      pregnancies and p=.07 when including second pregnancies). LARC satisfaction was
      high (80% happy/neutral, 73% would use LARC again, 81% would recommend to a
      friend). Baseline negative attitudes toward LARC (27%) were not clearly
      associated with satisfaction or early discontinuation. CONCLUSIONS: The decision
      to try LARC resulted in high continuation rates and substantial protection from
      unintended pregnancy over 24months. Despite participants' initial desires to
      begin short-acting regimens, they had high satisfaction with LARC. Voluntary
      decisions to try LARC will benefit large proportions of typical SARC users.
      IMPLICATIONS: Even women who do not necessarily view LARC as a first choice may
      have a highly satisfying experience and avoid unintended pregnancy if they try
      it.

PMID- 29470951
TI  - Serum level of long noncoding RNA H19 as a diagnostic biomarker of multiple
      myeloma.
AB  - Circulating long noncoding RNA (lncRNA) H19 has been reported to be a biomarker
      for cancer monitoring. The purpose of this study was to determine whether serum
      lncRNA could serve as a novel biomarker for the diagnosis of multiple myeloma
      (MM) and evaluate its value of clinical application. In our study, the expression
      of lncRNA H19 was up-regulated in 80 patients with MM and MM cell lines by RT-PCR
      analysis. Clinicopathological analysis showed the expression level of H19 could
      assist clinical staging, and the severity of the disease could be roughly
      determined according to the amount of H19 expressed in the patient serum. This is
      the first report to show that H19 was expressed in the serum of MM patients,
      suggesting that upregulation of serum lncRNA H19 may prove to be a novel
      biomarker for early diagnosis and clinical treatment of MM.

PMID- 29470952
TI  - Urinary myeloperoxidase to creatinine ratio as a new marker for monitoring
      treatment effects of urinary tract infection.
AB  - OBJECTIVE: We want to determine whether urinary myeloperoxidase to creatinine
      ratio could be served as a new marker for monitoring treatment effects of urinary
      tract infection or not. METHODS: A total of 328 patients suspected of UTI were
      enrolled in present study. Patients been received antibiotic therapy within two
      weeks were excluded (n = 26). Patients with urine contaminated specimens (n = 49)
      and negative urine culture results (n = 96) were also excluded, the remaining
      culture positive subjects (n = 157) were followed up for 7 to 14 days, finally, a
      total of 49 subjects were followed up and further divided into cure (n = 35) and
      none-cure (n = 14) subgroups according to urine culture results. MPO
      concentration was determined by immunoturbidimetric method and creatinine level
      was measured by creatinine enzyme method. Two sided P values < 0.05 were
      considered statistically significant. RESULTS: Urinary MCR level between before
      and after antibiotic treatment of cure group were (1437.1 +/- 1777.9 vs.48.3 +/-
      59.3, t = 4.608, P = 0.001), respectively. Urinary MCR level between before and
      after antibiotic treatment of none-cure group were (1633.1 +/- 2168.7 vs. 999.4
      +/- 1708.0, t = 1.809, P = 0.094), respectively. CONCLUSIONS: Urinary MCR could
      be served as a promising marker for monitoring treatment effects of urinary tract
      infection.

PMID- 29470953
TI  - Cat preantral follicle survival after prolonged cooled storage followed by
      vitrification.
AB  - The aim of this study was to investigate the impact of prolonged storage at 4 
      degrees C on survival of cat preantral follicles (PAFs) pre- and post
      vitrification. Ovaries were obtained from 12 queens and transported at 4 oC
      within 2-6 h. Parts of the ovaries were stored for an additional 24 h or 72 h.
      The ovarian cortex was dissected, analyzed for viability (neutral red - NR) and
      morphology (histology - HE and ultrastructural analysis by TEM) and vitrified. We
      used 2 mm biopsy punches to obtain equal size pieces as the experimental units.
      After NR assessment, each sample was fixed and embedded in paraffin for HE
      staining to determine the number of morphologically intact follicles. Another 2
      mm piece of ovary was subjected to TEM. NR viability assessment and HE results
      showed a similar tendency with PAF survival postvitrification even after
      prolonged cooling at 24 h and 72 h. With TEM, integrity of mitochondria, plasma
      and basal membranes as well as the presence of pre-granulose cells of PAFs were
      documented postvitrification for the control group and 24 h prolonged storage
      group, but not after 72 h storage. Our results showed that cat PAFs can survive
      prolonged storage followed by vitrification. The described set of techniques are
      applicable towards creating a gamete bank for endangered feline species.

PMID- 29470954
TI  - The optical properties of rat, porcine and human lenses in organ culture treated
      with dexamethasone.
AB  - Organ culturing of lenses is useful for testing the direct effect of moieties
      such as cations, glucose, oxygen, antioxidants or drugs on the lens. Lens opacity
      changes in organ cultured lenses have never been measured quantitatively. Our
      aims were twofold: to establish the time course of lens opacity changes in organ
      cultured rat, porcine and human lenses and to test the utility of our system to
      measure opacity changes in lenses treated with dexamethasone. Human, porcine and
      rat lenses were incubated with or without 5 MUM dexamethasone in minimum
      essential medium for 13 days. Lens absorbance and light scattering were measured
      using a spectrometer. Lens opacity was graded from lens photographs. Sixteen
      human lenses were obtained from 10 donors. Light scattering accounted for all of
      the absorbance of the human lens above 550 nm, 72% of the absorbance at 500 nm
      and 50% of the absorbance at 450 nm. Similarly, for the porcine lens, light
      scattering accounted for all of the absorbance above 400 nm and 40% of the
      absorbance at 350 nm. For the rat lens, scattering accounted for all of the
      absorbance above 325 nm, and 37% of the absorbance at 300 nm. In the rat lens
      spectrum, the broad absorbance peak near 600 nm was unique to the rat lens. After
      day five in organ culture, the level of light scattering, absorbance and optical
      grade of human lenses were higher in dexamethasone treated lenses compared with
      those without dexamethasone. Similar differences were observed for rat lenses
      after one day in organ culture. The opacity of porcine lenses did not change with
      dexamethasone treatment. In conclusion, this study showed that dexamethasone
      induced opacity in human and rat lenses could be measured which is important to
      future studies to test the positive or negative efficacy of moieties that cause
      or ameliorate cataract.

PMID- 29470955
TI  - PI3K regulates intraepithelial cell positioning through Rho GTP-ases in the
      developing neural tube.
AB  - Phosphatidylinositol 3-kinases (PI3Ks) are signal transducers of many biological
      processes. Class 1 A PI3Ks are hetero dimers formed by a regulatory and a
      catalytic subunit. We have used the developing chicken neural tube (NT) to study
      the roles played by PI3K during the process of cell proliferation and
      differentiation. Notably, we have observed that in addition to its well
      characterized anti apoptotic activity, PI3K also plays a crucial role in intra
      epithelial cell positioning, and unlike its role in survival that mainly depends
      on AKT, the activity in cell positioning is mediated by Rho GTPase family
      members. Additionally, we have observed that activating mutations of PI3K that
      are remarkably frequent in many human cancers, cause an unrestrained basal
      migration of the neuroepithelial cells that end up breaking through the basal
      membrane invading the surrounding mesenchymal tissue. The mechanism described in
      this work contribute not only to acquire a greater knowledge of the
      intraepithelial cell positioning process, but also give new clues on how
      activating mutations of PI3K contribute to cell invasion during the first stages
      of tumour dissemination.

PMID- 29470956
TI  - Metabolomic insights into the effects of thyroid hormone on Rana [Lithobates]
      catesbeiana metamorphosis using whole-body Matrix Assisted Laser
      Desorption/Ionization-Mass Spectrometry Imaging (MALDI-MSI).
AB  - Anuran metamorphosis involves the transformation of an aquatic tadpole into a
      juvenile frog. This process is completely dependent upon thyroid hormones (THs).
      Although much research has been focused on changes in gene expression programs
      during this postembryonic developmental period, transitions in the metabolic
      profiles are relatively poorly understood. Matrix Assisted Laser
      Desorption/Ionization-Mass Spectrometry Imaging (MALDI-MSI) is a technique that
      generates highly multiplexed mass spectra while retaining spatial location
      information on a thin tissue section. Reconstructed ion heat maps are correlated
      with morphology of the tissue section for biological interpretation. The present
      study is the first to use whole-body MALDI-MSI on tadpoles to gain insights into
      anuran metamorphosis. Approximately 1000 features were detected in each of five
      tissues examined (brain, eye, liver, notochord, and tail muscle) from
      premetamorphic North American bullfrog (Rana [Lithobates] catesbeiana) tadpoles.
      Of these detected metabolites, 1700 were unique and 136 were significantly
      affected by exposure to 50 nM thyroxine for 48 h. Of the significantly-affected
      metabolites, 64 features were tentatively identified using the MassTRIX
      annotation tool. All tissues revealed changes in lipophilic compounds including
      phosphatidylcholines, phosphatidylinositols, phosphatidylglycerols,
      phosphatidylethanolamines, and phosphatidylserines. These lipophilic compounds
      made up the largest portion of significantly-affected metabolites indicating that
      lipid signaling is a major target of TH action in frog tadpoles.

PMID- 29470957
TI  - Kaempferol 7-O-beta-D-glucoside isolated from the leaves of Cudrania tricuspidata
      inhibits LPS-induced expression of pro-inflammatory mediators through
      inactivation of NF-kappaB, AP-1, and JAK-STAT in RAW 264.7 macrophages.
AB  - Kaempferol 7-O-beta-D-glucoside (KPG), a natural flavonol isolated from Cudrania
      tricuspidata, has been reported to exert anti-cancer effects; however, its anti
      inflammatory effects have not yet been reported. In this study, we demonstrate
      the suppressive effect of KPG on the production of nitric oxide (NO),
      prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha), interleukin
      1beta (IL-1beta), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced
      RAW 264.7 macrophages and mouse bone marrow-derived macrophages. KPG
      downregulated the expression of inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) at the protein level and iNOS, COX-2, TNF-alpha, IL
      1beta, and IL-6 at the mRNA level in LPS-treated RAW 264.7 macrophages. Moreover,
      we elucidated the underlying molecular mechanism, demonstrating that KPG
      attenuated LPS-induced nuclear factor-kappaB (NF-kappaB) activation by decreasing
      p65 nuclear translocation, inhibiting kappaBalpha (IkappaBalpha)
      phosphorylation/degradation and IkappaB kinasealpha/beta (IKKalpha/beta)
      phosphorylation. KPG additionally reduced LPS-induced activator protein-1 (AP-1)
      activity by inhibiting c-Fos expression in the nucleus, though c-Jun was not
      affected. Furthermore, we revealed that KPG significantly abrogated the LPS
      induced phosphorylation of signal transducer and activator of transcription
      (STAT) 1 (Ser 727, Tyr 701) and STAT3 (Tyr 705) through inhibiting the
      phosphorylation of Janus kinase (JAK) 1 and JAK2, its upstream activating
      proteins. Taken together, our data suggest that KPG induces anti-inflammatory
      activity by blocking NF-kappaB, AP-1, and JAK-STAT signaling pathways in LPS
      treated RAW 264.7 macrophages, thus suppressing inflammatory mediators.

PMID- 29470958
TI  - Amentoflavone is a potent broad-spectrum inhibitor of human UDP
      glucuronosyltransferases.
AB  - Amentoflavone (AMF), an abundant natural biflavonoid found in many medicinal
      plants, displays various beneficial effects including anti-inflammatory, anti
      oxidative and anti-cancer. Despite the extensive studies on pharmacological
      activities, the toxicity or undesirable effects of AMF are rarely reported. In
      this study, the inhibitory effects of AMF on human UDP-glucuronosyltransferases
      (UGTs) were carefully investigated. AMF displayed strong inhibition towards most
      of human UGTs including UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4 and 2B17,
      with the IC50 values ranging from 0.12 MUM to 16.81 MUM. Inhibition constants
      (Ki) of AMF against various human UGTs varied from 0.29 MUM to 11.51 MUM. Further
      investigation demonstrated that AMF was a noncompetitive inhibitor of UGT1A1
      mediated NCHN-O-glucuronidation but functioned as a competitive inhibitor of
      UGT1A1 mediated 4-MU-O-glucuronidation. In addition, AMF was a competitive
      inhibitor of UGT1A4 mediated TFP-N-glucuronidation in both UGT1A4 and human liver
      microsomes, while functioned as a competitive inhibitor of UGT1A9 mediated
      propofol or 4-MU-O-glucuronidation. These findings demonstrated that AMF was a
      strong and broad-spectrum natural inhibitor of most human UGTs, which might bring
      potential risks of herb-drug interactions (HDIs) via UGT inhibition.
      Additionally, this study provided novel insights into the underlying mechanism of
      AMF-associated toxicity from the perspective of UGT inhibition.

PMID- 29470959
TI  - Differential effects of serotonin reuptake inhibitors fluoxetine and escitalopram
      on bone markers and microarchitecture in Wistar rats.
AB  - Evidence from several studies indicates that the long-term treatment of selective
      serotonin reuptake inhibitors (SSRIs) is associated with a decrease in bone mass
      and increase the risk of fractures. The present work evaluated and compared the
      effect of treatment with two SSRIs viz. fluoxetine and escitalopram on bone
      biomarkers (P1NP and betaCTX) in male Wistar rats. In addition, the effect of
      these drugs on bone microarchitecture of lumbar and tibia bones was carried out.
      Fluoxetine (8.2 mg/kg) treatment for 40 days significantly reduced (P < 0.01) the
      levels of the P1NP while escitalopram (2.0 mg/kg) was without such effects. Both
      drugs were devoid of any effects on bone resorption marker betaCTX. The pCREB
      levels were reduced by both the antidepressants but the reduction was
      significantly (P < 0.001) marked in case of fluoxetine. The micro-CT data
      revealed that fluoxetine, but not escitalopram, treatment resulted in reduced
      bone volume fraction, trabecular thickness and number while increased trabecular
      separation, trabecular pattern factor and connectivity density in the proximal
      tibial metaphysis. No significant changes were, however, discernible in lumbar
      bones. The study shows that fluoxetine reduces bone formation possibly through
      reduced pCREB mediated by the action of gut serotonin in osteoblasts and that
      escitalopram can be a better treatment option as far as adverse effects on bone
      are concerned.

PMID- 29470960
TI  - Establishment of reference intervals for the salivary cortisol circadian cycle,
      by electrochemiluminescence (ECLIA), in healthy adults.
AB  - OBJECTIVES: To determine salivary cortisol reference intervals in a healthy adult
      population, at 6 different time points during a 24-hour (h) period. METHODS: In a
      prospective study, salivary cortisol concentrations were measured upon waking,
      one-hour post-waking and at specific times of the day: at 12 h00, 16 h00, 20 h00
      and midnight. Samples were analyzed by the first and second-generation
      electrochemiluminescence assays (ECLIA) from Roche Cobas Cortisol(r). RESULTS:
      Salivary cortisol values were obtained from 134 healthy volunteers. Reference
      intervals for the first-generation assay were 6.14-33.19 nmol/L (95% prediction
      interval) at waking, 5.42-28.06 nmol/L one-hour post-waking, 3.62-16.23 nmol/L at
      12 h00, 2.78-15.27 nmol/L at 16 h00, 2.08-14.90 nmol/L at 20 h00 and 2.09-16.92
      nmol/L at midnight. Mean salivary cortisol values were 14.63 nmol/L at waking and
      6.44 nmol/L at midnight. Reference intervals for the second-generation assay were
      1.50-22.02 nmol/L (2.5th to 97.5th percentiles) at waking, 1.50-20.87 nmol/L one
      hour post-waking, 1.50-12.51 nmol/L at 12 h00, 1.50-13.03 nmol/L at 16 h00, 1.50
      9.52 nmol/L at 20 h00 and 1.50-6.28 nmol/L at midnight. Values for the second
      generation assay at all 6 different time points were almost half of the first
      generation assay. The second-generation assay showed a better correlation with LC
      MS/MS (r = 0,97). CONCLUSION: Our study confirms that reference intervals for
      salivary cortisol are not comparable across first and second-generation Roche
      Cobas Cortisol(r) assays. Furthermore, the second-generation assay has a better
      correlation with LC-MS/MS and a better analytical performance (accuracy and
      precision).

PMID- 29470961
TI  - Mechano-growth factor protects against mechanical overload induced damage and
      promotes migration of growth plate chondrocytes through RhoA/YAP pathway.
AB  - Epiphyseal growth plate is highly dynamic tissue which is controlled by a variety
      of endocrine, paracrine hormones, and by complex local signaling loops and
      mechanical loading. Mechano growth factor (MGF), the splice variant of the IGF-I
      gene, has been discovered to play important roles in tissue growth and repair.
      However, the effect of MGF on the growth plate remains unclear. In the present
      study, we found that MGF mRNA expression of growth plate chondrocytes was
      upregulated in response to mechanical stimuli. Treatment of MGF had no effect on
      growth plate chondrocytes proliferation and differentiation. But it could inhibit
      growth plate chondrocytes apoptosis and inflammation under mechanical overload.
      Moreover, both wound healing and transwell assay indicated that MGF could
      significantly enhance growth plate chondrocytes migration which was accompanied
      with YAP activation and nucleus translocation. Knockdown of YAP with YAP siRNA
      suppressed migration induced by MGF, indicating the essential role of YAP in MGF
      promoting growth plate chondrocytes migration. Furthermore, MGF promoted YAP
      activation through RhoA GTPase mediated cytoskeleton reorganization, RhoA
      inhibition using C3 toxin abrogated MGF induced YAP activation. Importantly, we
      found that MGF promoted focal adhesion(FA) formation and knockdown of YAP with
      YAP siRNA partially suppressed the activation of FA kinase, implying that YAP is
      associated with FA formation. In conclusion, MGF is an autocrine growth factor
      which is regulated by mechanical stimuli. MGF could not only protect growth plate
      chondrocytes against damage by mechanical overload, but also promote migration
      through activation of RhoA/YAP signaling axis. Most importantly, our findings
      indicate that MGF promote cell migration through YAP mediated FA formation to
      determine the FA-cytoskeleton remodeling.

PMID- 29470963
TI  - Autoantibodies Hurt: Transfer of Patient-Derived CASPR2 Antibodies Induces
      Neuropathic Pain in Mice.
AB  - In this issue of Neuron, Dawes et al. (2018) show that CASPR2 antibodies (Abs)
      isolated from patients bind specifically to primary afferent cell bodies and
      induce neuropathic pain in mice. Consequent decreased expression of Kv1 channels
      and their aberrant localization along myelinated axons explain the observed
      hyperexcitability and pain.

PMID- 29470962
TI  - Indomethacin induced glioma apoptosis involving ceramide signals.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are increasingly implicated in the
      prevention and treatment of cancers apart from their known inhibitory effects on
      eicosanoid production. One of the NSAIDs, indomethacin, in particular shows
      promising antineoplastic outcome against glioma. To extend such finding, we here
      studied in human H4 and U87 glioma cells the possible involvement of the
      ceramide/protein phosphatase 2 A (PP2A)/Akt axis in the indomethacin-induced
      apoptosis. We found that the induced apoptosis was accompanied by a series of
      biochemical events, including intracellular ceramide generation, PP2A activation,
      Akt dephosphorylation, Mcl-1 and FLICE inhibiting protein (FLIP) transcriptional
      downregulation, Bax mitochondrial distribution, and caspase 3 activation. Such
      events were also duplicated with a cell-permeable C2-ceramide and Akt inhibitor
      LY294002. Pharmacological inhibition of ceramide synthase by fumonisin B1 and
      PP2A by okadaic acid moderately attenuated indomethacin-induced Akt
      dephosphorylation along with the apoptosis. Results suggested that the
      ceramide/PP2A/Akt axis is involved in the apoptosis and a possible cyclooxygenase
      independent target for indomethacin. Furthermore, apoptosis regulatory proteins
      such as Mcl-1 and FLIP are potential downstream effectors of this axis and their
      downregulation could turn on the apoptotic program.

PMID- 29470964
TI  - Everything in Its Right Place: A Prefrontal-Midbrain Circuit for Contextual Fear
      Discrimination.
AB  - In this issue of Neuron, Rozeske et al. (2018) use an ingenuous behavioral
      paradigm to change pertinent sensory stimuli defining a given context to
      interrogate how the dorsomedial prefrontal cortex (dmPFC) and periaqueductal gray
      (PAG) interact during contextual fear discrimination.

PMID- 29470965
TI  - Causal Evidence for a Neural Component of Spatially Global Hemodynamic Signals.
AB  - In this issue of Neuron, Turchi et al. (2018) reversibly inactivate the basal
      forebrain to show that this region magnifies global neocortical signal
      fluctuations without altering the topography of canonical resting-state networks.
      Thus, spatially diffuse signals measurable via functional neuroimaging may track
      large-scale neuromodulatory state changes in the primate brain.

PMID- 29470966
TI  - Untangling Neural Representations in the Motor Cortex.
AB  - How the brain generates accurate movement is a long-standing problem in
      neuroscience. In this issue of Neuron, Russo et al. (2018) argue that population
      activity in motor cortex does not represent muscle patterns but rather untangled
      neural trajectories that are robust to noise.

PMID- 29470967
TI  - A Spotlight on Appetite.
AB  - Remarkably few hormones have been identified that stimulate appetite. The recent
      discovery of asprosin, a hormone that activates AgRP neurons to increase food
      intake and body weight, begins to fill this gap (Duerrschmid et al., 2017; Romere
      et al., 2016).

PMID- 29470968
TI  - Multiple Sclerosis: Mechanisms and Immunotherapy.
AB  - Multiple sclerosis (MS) is an autoimmune disease triggered by environmental
      factors that act on a genetically susceptible host. It features three clinical
      stages: a pre-clinical stage detectable only by MRI; a relapsing-remitting (RRMS)
      stage characterized by episodes of neurologic dysfunction followed by resolution;
      and a progressive stage, which usually evolves from the relapsing stage. Advances
      in our understanding of the immune mechanisms that contribute to MS have led to
      more than ten FDA-approved immunotherapeutic drugs that target effector T cells,
      regulatory cells, B cells, and cell trafficking into the nervous system. However,
      most drugs for relapsing MS are not effective in treating progressive disease.
      Progressive MS features a compartmentalized immune response in the central
      nervous system, involving microglia cells and astrocytes, as well as immune
      independent processes that drive axonal dysfunction. Major challenges for MS
      research involve understanding the mechanisms of disease progression, developing
      treatment for progressive MS, and determining the degree to which progressive
      disease can be prevented by early treatment. Key priorities for MS research
      include developing biomarkers, personalized medicine and advanced imaging, and a
      better understanding of the microbiome. With a better understanding of the
      genetic and epidemiological aspects of this disease, approaches to prevent MS are
      now also being considered.

PMID- 29470970
TI  - Comparisons Between Histology and Optical Coherence Tomography Angiography of the
      Periarterial Capillary-Free Zone.
AB  - PURPOSE: To use the capillary-free zone along retinal arteries, a physiologic
      area of superficial avascularization, as an anatomic paradigm to investigate the
      reliability of optical coherence tomography angiography (OCTA) for visualizing
      the deep retinal circulation. DESIGN: Validity analysis and laboratory
      investigation. METHODS: Five normal human donor eyes (mean age 69.8 years) were
      perfusion-labeled with endothelial antibodies and the capillary networks of the
      perifovea were visualized using confocal scanning laser microscopy. Regions of
      the capillary-free zone along the retinal artery were imaged using OCTA in 16
      normal subjects (age range 24-51 years). Then, 3 * 3-mm scans were acquired using
      the RTVue XR Avanti (ver. 2016.1.0.26; Optovue, Inc, Fremont, California, USA),
      PLEX Elite 9000 (ver. 1.5.0.15909; Zeiss Meditec, Inc, Dublin, California, USA),
      Heidelberg Spectralis OCT2 (Family acquisition module 6.7.21.0; Heidelberg
      Engineering, Heidelberg, Germany), and DRI-OCT Triton (Ver. 1.1.1; Topcon Corp,
      Tokyo, Japan). Images of the superficial plexus, deep vascular plexus, and a slab
      containing all vascular plexuses were generated using manufacturer-recommended
      default settings. Comparisons between histology and OCTA were performed. RESULTS:
      Histologic analysis revealed that the capillary-free zone along the retinal
      artery was confined to the plane of the superficial capillary plexus and did not
      include the intermediate and deep capillary plexuses. Images derived from OCTA
      instruments demonstrated a prominent capillary-free zone along the retinal artery
      in slabs of the superficial plexus, deep plexus, and all capillary plexuses. The
      number of deep retinal capillaries seen in the capillary-free zone was
      significantly greater on histology than on OCTA (P < .001). CONCLUSION: Using the
      capillary-free zone as an anatomic paradigm, we show that the deep vascular beds
      of the retina are not completely visualized using OCTA. This may be a limitation
      of current OCTA techniques.

PMID- 29470971
TI  - Use of Autologous Serum Tears for the Treatment of Ocular Surface Disease From
      Patients With Systemic Autoimmune Diseases.
AB  - PURPOSE: To describe the safety and efficacy of autologous serum tears (AST) in
      managing ocular surface disease resistant to conventional therapy in patients
      with systemic autoimmune disease(s). DESIGN: Retrospective, interventional case
      series. METHODS: Records of patients from 2009 to 2015 with systemic autoimmune
      disease treated with AST (20%-50%) for chronic surface disease were analyzed.
      Standardized measures of subjective dry eye symptoms, objective dry eye staining
      of the cornea, and slit-lamp findings including punctate epithelial erosion
      (PEE), filamentary keratopathy (FK), and corneal epithelial defects (KED) were
      compared during first and last visit. We attempted to standardize outcomes by
      creating a scale from 1 to 4 for subjective and objective components: worsening
      (1), no improvement (2), partial improvement (3), and complete resolution (4).
      RESULTS: Fifty-one patients (101 eyes) were included. The mean age was 59.8 +/-
      13.2 years (72.5% female). Average use of AST was 14.3 +/- 11.7 months. Complete
      objective improvement of initial slit-lamp findings was achieved in 30% and
      partial improvement in 55% of eyes. Presence of PEE, FK, and KED decreased from
      92.1% to 52.5% (P < .001), from 22.8% to 9.9% (P = .02), and from 5% to 2% (P =
      .44) of the eyes, respectively. Full subjective improvement of symptoms was
      achieved in 34.6%, partial in 50.5%, and none in 14.9% of patients. No adverse
      side effects were noted during follow-up. CONCLUSIONS: AST are a safe and
      effective adjunct therapy in improving both objective signs and subjective
      symptoms of ocular surface disorders associated with systemic autoimmune
      disease(s).

PMID- 29470972
TI  - Influence of Nasal Tear Osmolarity on Ocular Symptoms Related to Dry Eye Disease.
AB  - PURPOSE: To investigate relationships between local tear osmolarity and tear film
      characteristics and dry eye disease (DED) symptoms. DESIGN: Prospective, cross
      sectional, observational study. METHODS: Nasal and temporal tear osmolarity were
      measured in subjects with DED. The difference between nasal and temporal tears
      (OSM difference) was then calculated. Ocular symptoms were evaluated and tear
      break-up time (TBUT), corneal fluorescein staining score (CFSS), eyelid
      hyperemia, and tear production were measured. Correlations between DED symptoms
      and nasal tear osmolarity, temporal tear osmolarity, OSM difference, and tear
      film characteristics were evaluated using Pearson correlation analyses. Subjects
      were divided into 3 groups based on OSM difference: the temporal group had a
      temporal osmolarity > nasal osmolarity, the nasal group had a temporal osmolarity
      < nasal osmolarity, and the equal group had an OSM difference < 10 mOsm/L.
      RESULTS: Forty-eight eyes of 48 subjects were included. Eleven eyes were in the
      temporal group, 17 eyes were in the equal group, and 20 eyes were in the nasal
      group. Temporal osmolarity, nasal osmolarity, and OSM difference were not
      correlated with TBUT, CFSS, lid hyperemia, or tear production. Nasal tear
      osmolarity was correlated with cold sensitivity frequency (r = 0.298, P = .040),
      foreign body sensation severity (r = 0.293, P = .043), and light sensitivity
      severity (r = 0.293, P = .043). Additionally, OSM difference was correlated with
      daily symptom frequency (r = 0.339, P = .019). CONCLUSIONS: Nasal tear osmolarity
      and OSM difference play an important role in DED symptoms. Lid hyperemia, TBUT,
      CFSS, and tear secretion volume are not significantly affected by tear
      osmolarity. It is important to measure both nasal and temporal tear osmolarity
      when evaluating patients with DED.

PMID- 29470969
TI  - Neuromodulation of Attention.
AB  - Attention is critical to high-level cognition and attention deficits are a
      hallmark of neurologic and neuropsychiatric disorders. Although years of research
      indicates that distinct neuromodulators influence attentional control, a
      mechanistic account that traverses levels of analysis (cells, circuits, behavior)
      is missing. However, such an account is critical to guide the development of next
      generation pharmacotherapies aimed at forestalling or remediating the global
      burden associated with disorders of attention. Here, we summarize current
      neuroscientific understanding of how attention affects single neurons and
      networks of neurons. We then review key results that have informed our
      understanding of how neuromodulation shapes these neuron and network properties
      and thereby enables the appropriate allocation of attention to relevant external
      or internal events. Finally, we highlight areas where we believe hypotheses can
      be formulated and tackled experimentally in the near future, thereby critically
      increasing our mechanistic understanding of how attention is implemented at the
      cellular and network levels.

PMID- 29470973
TI  - Long-term Surgical Outcomes for Large-angle Infantile Esotropia.
AB  - PURPOSE: To report the long-term surgical outcomes for a cohort of children with
      large-angle infantile esotropia. DESIGN: Multicenter, nonrandomized clinical
      study. METHODS: Setting: Two tertiary-care pediatric hospitals. STUDY POPULATION:
      Children with large-angle (>=55 prism diopters) infantile esotropia.
      INTERVENTION: Surgical treatment of infantile esotropia. MAIN OUTCOME MEASURE:
      Success rate at final follow-up (postoperative deviation <= 10 prism diopters and
      no need for retreatment). RESULTS: A total of 88 patients with large-angle
      infantile esotropia were treated during the 13-year study period. Treatment was
      bilateral medial rectus muscle recessions in 70 patients, botulinum toxin
      augmented surgery in 15 patients, and 3-muscle surgery in 3 patients. After a
      mean follow-up of 40 months, 20 patients (23%) had a successful outcome compared
      to 68 treatment failures (77%). Of the 68 treatment failures, 59 had residual or
      recurrent esotropia and 9 had sequential exotropia. On multivariate logistic
      regression, treatment modality was the only factor significantly associated with
      a successful outcome. Specifically, patients treated with botulinum toxin
      augmented surgery were more likely to have a successful outcome compared to
      patients treated with bilateral medial rectus muscle recessions. For the 26
      patients (30%) who underwent retreatment, the mean number of procedures was 2.1,
      and 7 (27%) had a deviation of <=10 prism diopters at final follow-up.
      CONCLUSIONS: The overall success rate for treatment of large-angle infantile
      esotropia was poor in this cohort, with most failures owing to recurrent or
      residual esotropia. Botulinum toxin-augmented surgery was associated with a
      higher success rate at final follow-up.

PMID- 29470974
TI  - A step towards standardization: A method for end-point titer determination by
      fluorescence index of an automated microscope. End-point titer determination by
      fluorescence index.
AB  - OBJECTIVES: Indirect Immunofluorescence (IIF) is widely considered the Gold
      Standard for Antinuclear Antibody (ANA) screening. However, the high inter-reader
      variability remains the major disadvantage associated with ANA testing and the
      main reason for the increasing demand of the computer-aided immunofluorescence
      microscope. Previous studies proposed the quantification of the fluorescence
      intensity as an alternative for the classical end-point titer evaluation.
      However, the different distribution of bright/dark light linked to the nature of
      the self-antigen and its location in the cells result in different mean
      fluorescence intensities. The aim of the present study was to correlate
      Fluorescence Index (F.I.) with end-point titers for each well-defined ANA
      pattern. METHODS: Routine serum samples were screened for ANA testing on HEp-2000
      cells using Immuno Concepts Image Navigator System, and positive samples were
      serially diluted to assign the end-point titer. A comparison between F.I. and end
      point titers related to 10 different staining patterns was made. RESULTS:
      According to our analysis, good technical performance of F.I. (97% sensitivity
      and 94% specificity) was found. A significant correlation between quantitative
      reading of F.I. and end-point titer groups was observed using Spearman's test and
      regression analysis. A conversion scale of F.I. in end-point titers for each
      recognized ANA-pattern was obtained. CONCLUSIONS: The Image Navigator offers the
      opportunity to improve worldwide harmonization of ANA test results. In
      particular, digital F.I. allows quantifying ANA titers by using just one sample
      dilution. It could represent a valuable support for the routine laboratory and an
      effective tool to reduce inter- and intra-laboratory variability.

PMID- 29470975
TI  - High-throughput screening of T7 phage display and protein microarrays as a
      methodological approach for the identification of IgE-reactive components.
AB  - Olive pollen and yellow mustard seeds are major allergenic sources with high
      clinical relevance. To aid with the identification of IgE-reactive components,
      the development of sensitive methodological approaches is required. Here, we have
      combined T7 phage display and protein microarrays for the identification of
      allergenic peptides and mimotopes from olive pollen and mustard seeds. The
      identification of these allergenic sequences involved the construction and
      biopanning of T7 phage display libraries of mustard seeds and olive pollen using
      sera from allergic patients to both biological sources together with the
      construction of phage microarrays printed with 1536 monoclonal phages from the
      third/four rounds of biopanning. The screening of the phage microarrays with
      individual sera from allergic patients enabled the identification of 10 and 9 IgE
      reactive unique amino acid sequences from olive pollen and mustard seeds,
      respectively. Five immunoreactive amino acid sequences displayed on phages were
      selected for their expression as His6-GST tag fusion proteins and validation.
      After immunological characterization, we assessed the IgE-reactivity of the
      constructs. Our results show that protein microarrays printed with T7 phages
      displaying peptides from allergenic sources might be used to identify allergenic
      components -peptides, proteins or mimotopes- through their screening with
      specific IgE antibodies from allergic patients.

PMID- 29470976
TI  - Evaluation of methods to reduce background using the Python-based ELISA_QC
      program.
AB  - Almost all immunological approaches [immunohistochemistry, enzyme-linked
      immunosorbent assay (ELISA), Western blot], that are used to quantitate specific
      proteins have had to address high backgrounds due to non-specific reactivity. We
      report here for the first time a quantitative comparison of methods for reduction
      of the background of commercial biotinylated antibodies using the Python-based
      ELISA_QC program. This is demonstrated using a recombinant humanized anti-cocaine
      monoclonal antibody. Several approaches, such as adjustment of the incubation
      time and the concentration of blocking agent, as well as the dilution of
      secondary antibodies, have been explored to address this issue. In this report,
      systematic comparisons of two different methods, contrasted with other more
      traditional methods to address this problem are provided. Addition of heparin
      (HP) at 1 MUg/ml to the wash buffer prior to addition of the secondary
      biotinylated antibody reduced the elevated background absorbance values (from a
      mean of 0.313 +/- 0.015 to 0.137 +/- 0.002). A novel immunodepletion (ID) method
      also reduced the background (from a mean of 0.331 +/- 0.010 to 0.146 +/- 0.013).
      Overall, the ID method generated more similar results at each concentration of
      the ELISA standard curve to that using the standard lot 1 than the HP method, as
      analyzed by the Python-based ELISA_QC program. We conclude that the ID method,
      while more laborious, provides the best solution to resolve the high background
      seen with specific lots of biotinylated secondary antibody.

PMID- 29470977
TI  - The unfolded protein response in ischemic heart disease.
AB  - Ischemic heart disease is a severe stress condition that causes extensive
      pathological alterations and triggers cardiac cell death. Accumulating evidence
      suggests that the unfolded protein response (UPR) is strongly induced by
      myocardial ischemia. The UPR is an evolutionarily conserved cellular response to
      cope with protein-folding stress, from yeast to mammals. Endoplasmic reticulum
      (ER) transmembrane sensors detect the accumulation of unfolded proteins and
      stimulate a signaling network to accommodate unfolded and misfolded proteins.
      Distinct mechanisms participate in the activation of three major signal pathways,
      viz. protein kinase RNA-like ER kinase, inositol-requiring protein 1, and
      activating transcription factor 6, to transiently suppress protein translation,
      enhance protein folding capacity of the ER, and augment ER-associated degradation
      to refold denatured proteins and restore cellular homeostasis. However, if the
      stress is severe and persistent, the UPR elicits inflammatory and apoptotic
      pathways to eliminate terminally affected cells. The ER is therefore recognized
      as a vitally important organelle that determines cell survival or death. Recent
      studies indicate the UPR plays critical roles in the pathophysiology of ischemic
      heart disease. The three signaling branches may elicit distinct but overlapping
      effects in cardiac response to ischemia. Here, we outline the findings and
      discuss the mechanisms of action and therapeutic potentials of the UPR in the
      treatment of ischemic heart disease.

PMID- 29470978
TI  - Contractile responses to endothelin-1 are regulated by PKC phosphorylation of
      cardiac myosin binding protein-C in rat ventricular myocytes.
AB  - The shortening of sarcomeres that co-ordinates the pump function of the heart is
      stimulated by electrically-mediated increases in [Ca2+]. This process of
      excitation-contraction coupling (ECC) is subject to modulation by neurohormonal
      mediators that tune the output of the heart to meet the needs of the organism.
      Endothelin-1 (ET-1) is a potent modulator of cardiac function with effects on
      contraction amplitude, chronotropy and automaticity. The actions of ET-1 are
      evident during normal adaptive physiological responses and increased under
      pathophysiological conditions, such as following myocardial infarction and during
      heart failure, where ET-1 levels are elevated. In myocytes, ET-1 acts through ETA
      or ETB-G protein-coupled receptors (GPCRs). Although well studied in atrial
      myocytes, the influence and mechanisms of action of ET-1 upon ECC in ventricular
      myocytes are not fully resolved. We show in rat ventricular myocytes that ET-1
      elicits a biphasic effect on fractional shortening (initial transient negative
      and sustained positive inotropy) and increases the peak amplitude of systolic
      Ca2+ transients in adult rat ventricular myocytes. The negative inotropic phase
      was ETB receptor-dependent, whereas the positive inotropic response and increase
      in peak amplitude of systolic Ca2+ transients required ETA receptor engagement.
      Both effects of ET-1 required phospholipase C (PLC)-activity, although distinct
      signalling pathways downstream of PLC elicited the effects of each ET receptor.
      The negative inotropic response involved inositol 1,4,5-trisphosphate (InsP3)
      signalling and protein kinase C epsilon (PKCepsilon). The positive inotropic
      action and the enhancement in Ca2+ transient amplitude induced by ET-1 were
      independent of InsP3 signalling, but suppressed by PKCepsilon. Serine 302 in
      cardiac myosin binding protein-C was identified as a PKCepsilon substrate that
      when phosphorylated contributed to the suppression of contraction and Ca2+
      transients by PKCepsilon following ET-1 stimulation. Thus, our data provide a new
      role and mechanism of action for InsP3 and PKCepsilon in mediating the negative
      inotropic response and in restraining the positive inotropy and enhancement in
      Ca2+ transients following ET-1 stimulation.

PMID- 29470979
TI  - Transcriptional information revealed differentially expressed circular RNAs in
      facet joint osteoarthritis.
AB  - Circular RNAs are newly identified RNAs that regulate gene expression and execute
      various biological activities. Facet joint osteoarthritis (FJOA) is a severe
      facet joint cartilage degeneration disease that induces chronic low back pain to
      a larger population. The molecular mechanisms of FJOA, especially the presence
      and changes of circular RNAs in FJOA have not been investigated. In the current
      study, we analyzed RNA deep sequencing outcomes from healthy control group and
      FJOA group, identified and annotated circular RNAs, and determined the
      expressions of circular RNAs. Differentially expressed circular RNAs in the FJOA
      group were then screened and the host genes of these differentially expressed
      circular RNAs were functional analyzed by Gene Ontology (GO), Kyoto Enrichment of
      Genes and Genomes (KEGG), and protein-protein interaction network analysis. Seven
      circRNAs were arbitrarily selected to confirm the trustworthiness of these
      profiles by quantitative qRT-PCR. The potential binding sites of microRNAs
      (miRNAs) and identified circular RNAs were also predicted. Our current study
      provided valuable bioinformation regarding circular RNAs in FJOA and expanded our
      knowledge of FJOA.

PMID- 29470980
TI  - Graphene coating on the surface of CoCrMo alloy enhances the adhesion and
      proliferation of bone marrow mesenchymal stem cells.
AB  - The objective was to investigate whether a graphene coating could improve the
      surface bioactivity of a cobalt-chromium-molybdenum-based alloy (CoCrMo).
      Graphene was produced by chemical vapor deposition and transferred to the surface
      of the CoCrMo alloy using an improved wet transfer approach. The morphology of
      the samples was observed, and the adhesion force and stabilization of graphene
      coating were analyzed by a nanoscratch test and ultrasonication test. In an in
      vitro study, the adhesion and proliferation of bone marrow mesenchymal stem cells
      (BMSCs) cultured on the samples were quantified via an Alamar Blue assay and cell
      counting kit-8 (CCK-8) assay. The results showed that it is feasible to apply
      graphene to modify the surface of a CoCrMo alloy, and the enhancement of the
      adhesion and proliferation of BMSCs was also shown in the present study. In
      conclusion, graphene exhibits considerable potential for enhancing the surface
      bioactivity of CoCrMo alloy.

PMID- 29470981
TI  - GhoT of the GhoT/GhoS toxin/antitoxin system damages lipid membranes by forming
      transient pores.
AB  - GhoT is a bacterial toxin of the type V toxin/antitoxin system that allows
      Escherichia coli to reduce its metabolism in response to oxidative and bile
      stress. GhoT functions by increasing membrane permeability and reducing both ATP
      levels and the proton motive force. However, how GhoT damages the inner membrane
      has not been elucidated. Here we investigated how GhoT damages membranes by
      studying its interaction with lipid bilayers and determined that GhoT does not
      cause macroscopic disruption of the lipid bilayer to increase membrane
      permeability to the dye carboxyfluorescein. Using circular dichroism, we found
      that GhoT forms an alpha helical structure in lipid bilayers that agrees with the
      structure predicted by the I-TASSER protein structure prediction program. The
      structure generated using I-TASSER was used to conduct coarse-grained molecular
      dynamics simulations, which indicate that GhoT damages the cell membrane, as a
      multimer, by forming transient transmembrane pores.

PMID- 29470982
TI  - RIP3 deficiency protects against traumatic brain injury (TBI) through suppressing
      oxidative stress, inflammation and apoptosis: Dependent on AMPK pathway.
AB  - Traumatic brain injury (TBI) is a leading cause of disability and mortality in
      young adults worldwide. The pathophysiology is not fully understood. Programmed
      necrosis (necroptosis) is a newly identified mechanism of cell death combining
      features of both apoptosis and necrosis. Receptor-interacting protein 3 (RIP3)
      plays an important role in programmed necrosis. However, the effect of RIP3
      related pathway in TBI is little to be known. We attempted to explore the
      significance of RIP3 in regulating TBI in vivo. Significantly, TBI induced over
      expression of RIP3 in the hippocampus of mice, as well as RIP1 and phosphorylated
      mixed lineage kinase domain-like protein (MLKL). Mice after TBI exhibited
      cognitive dysfunction and activation of glia cells, which were significantly
      attenuated by RIP3-knockout (KO). Moreover, inflammation and oxidative stress in
      hippocampus were markedly induced by TBI in wild type (WT) mice. Of note, the
      reduction of pro-inflammatory cytokines and oxidants was observed in RIP3
      deficient mice, which was linked to the blockage of NLR pyrin domain containing 3
      (NLRP3)/apoptosis-associated speck-like protein containing a CARD (ASC)/Caspase-1
      and kelch-like ECH-associated protein 1 (Keap 1) pathways. Further, TBI induced
      hippocampus apoptosis, evidenced by the increase of cleaved Caspase-8/-3 and poly
      (ADP)-ribose polymerase (PARP) in WT mice, whereas being decreased by RIP3
      knockout. In addition, RIP3 knockout led to phosphorylation of AMP-activated
      protein kinase alpha (AMPKalpha) in hippocampus of mice after TBI. And of note,
      the in vitro findings indicated that RIP3-ablation attenuated oxidative stress,
      inflammation and apoptosis in astrocytes, which was dependent on AMPKalpha
      activation. Together, suppressing RIP3 might be served as a therapeutic target
      against brain injury through inhibiting inflammation, oxidative stress and
      apoptosis.

PMID- 29470983
TI  - Development of a functional thyroid model based on an organoid culture system.
AB  - The low turnover rate of thyroid follicular cells and the lack of a long-term
      thyroid cell culture system have hampered studies of thyroid carcinogenesis. We
      have now established a thyroid organoid culture system that supports thyroid cell
      proliferation in vitro. The established mouse thyroid organoids performed thyroid
      functions including thyroglobulin synthesis, iodide uptake, and the production
      and release of thyroid hormone. Furthermore, transplantation of the organoids
      into recipient mice resulted in the formation of normal thyroid-like tissue
      capable of iodide uptake and thyroglobulin production in vivo. Finally, forced
      expression of oncogenic NRAS (NRASQ61R) in thyroid organoids established from p53
      knockout mice and transplantation of the manipulated organoids into mouse
      recipients generated a model of poorly differentiated thyroid cancer. Our
      findings suggest that this newly developed thyroid organoid culture system is a
      potential research tool for the study of thyroid physiology and pathology
      including thyroid cancer.

PMID- 29470984
TI  - Ribosome biogenesis protein Urb2 regulates hematopoietic stem cells development
      via P53 pathway in zebrafish.
AB  - Ribosome biogenesis is a significant process in cells. Dysfunction in this
      process will result in the defects of protein synthesis and consequently cause
      the development of specific diseases called ribosomopathies. Mutations in
      ribosome biogenesis protein Rps19, Rpl5, or Rpl11 can lead to hematopoietic
      defects in human, thus triggering the disease Diamond Blackfan anemia. However,
      the regulatory mechanisms of ribosome biogenesis in hematopoiesis remain
      incompletely understood. In this study, we describe a zebrafish mutant cq42,
      which carries a nonsense mutation in the gene that encodes ribosome biogenesis 2
      homolog (Urb2). Urb2 is strongly expressed in the caudal hematopoietic tissue
      (CHT) during hematopoietic stem cells (HSCs) expanding. Molecular
      characterization of urb2cq42 larvae suggest that urb2 deficiency notably decrease
      the population of HSCs in CHT and early T cells in thymus. Further analysis shows
      that compromised cell proliferation and superfluous apoptosis are observed in the
      CHT of urb2cq42 mutant. P53 pathway is upregulated in the urb2cq42 larvae and
      loss-of-function of P53 can fully rescue the hematopoietic defects in urb2cq42
      mutant. These data demonstrate that urb2 is essential for HSCs development
      through the regulation of P53 pathway.

PMID- 29470985
TI  - Cytoplasmic p53 contributes to the removal of uracils misincorporated by HIV-1
      reverse transcriptase.
AB  - HIV-1 reverse transcriptase (RT) in the cytoplasm of HIV-infected cells
      efficiently inserts the non-canonical dUTP into the proviral DNA, and extends the
      dU-terminated DNA. The misincorporation of dUTP leads to mutagenesis, and uracils
      can down-regulate viral gene expression. However, uracilation might also protect
      HIV DNA from auto-integration in the cytoplasm. Tumor suppressor p53 protein,
      exhibiting inherent 3'->5' exonuclease activity, provides a potential host
      derived repair mechanism during HIV reverse transcription for the
      misincorporation of various wrong nucleotides, leading to both base-base
      mismatches and incorporated non-canonical ribonucleotides. Since the presence of
      proofreading activity is essential for DNA synthesis accuracy, we elucidated the
      potential involvement of cytoplasmic p53 in the U-editing activities during
      insertion of dUTP into DNA by recombinant HIV-1 RT (using isogenic p53-proficient
      and -deficient HCT116 cells). The biochemical data show that p53 in cytoplasm can
      participate through the intermolecular pathway in a dU-damage-associated repair
      mechanism by its ability to remove preformed 3'-terminal dUs, thus preventing
      further extension of 3' dU-terminated primer during DNA synthesis by HIV-1 RT.
      The specific depletion of p53 from cytoplasmic lysates of repair-proficient p53
      harboring cells reduced this negative effect. Accordingly, the increased
      abundance of p53 in nutlin-treated cells correlates with enhanced error
      correction functions, namely, removal of incorporated uracil. The data
      substantiate the significance of p53 as a potential proofreader for removal of
      non-canonical dUTP from HIV DNA, thus preventing the consequences of dUTP
      misincorporation in cell-type specific infectivity of HIV.

PMID- 29470986
TI  - Silencing of LncRNA-HOTAIR decreases drug resistance of Non-Small Cell Lung
      Cancer cells by inactivating autophagy via suppressing the phosphorylation of
      ULK1.
AB  - Drug resistance is an important factor leading to the recurrence and metastasis
      of Non-Small Cell Lung Cancer (NSCLC). Long non-coding RNAs (LncRNAs) play
      important roles in drug resistance of tumor cells. The aim of our study was to
      investigate the mechanism of LncRNA-HOTAIR in regulating drug resistance of NSCLC
      cells. Our data indicated that HOTAIR was overexpressed in NSCLC cell lines.
      Silencing of HOTAIR decreased cell proliferation and increased apoptosis of NSCLC
      cells (A549). Besides that, HOTAIR shRNA transfection suppressed drug resistance
      of A549 cells to Crizotinib by more effectively inhibiting cell viability and
      promoting apoptosis compared with HOTAIR scramble group. Moreover, silencing of
      HOTAIR decreased the number of LC3+ puncta and the expression of Beclin1, p-ULK1
      and the ratio of LC3 II/I/in Crizotinib treated A549 cells, indicating that
      silencing of HOTAIR decreased drug resistance of NSCLC cells might through
      inhibiting autophagy via the ULK1 pathway. In order to further prove our
      conclusion, Rapamycin (Rapa), an autophagy inducer, was used in our study. With
      the adjunction of Rapa, obvious autophagy was induced by increasing the number of
      LC3+ puncta, the ratio of LC3 II/I and the expression of p-ULK1 compared with
      Crizotinib + HOTAIR shRNA group. What is more, the activation of autophagy
      abolished the effect of HOTAIR shRNA on decreasing drug resistance by increasing
      cell viability and decreasing cell apoptosis. These results supported our
      conclusion that silencing of HOTAIR decreased drug resistance of NSCLC cells to
      Crizotinib through inhibition of autophagy via suppressing phosphorylation of
      ULK1.

PMID- 29470987
TI  - Angiotensin-II regulates dosing time-dependent intratumoral accumulation of
      macromolecular drug formulations via 24-h blood pressure rhythm in tumor-bearing
      mice.
AB  - One approach to increasing pharmacotherapy effects is administering drugs at
      times of day when they are most effective and/or best tolerated. Circadian
      variation in expression of pharmacokinetics- and pharmacodynamics-related genes
      was shown to contribute to dosing time-dependent differences in therapeutic
      effects of small molecule drugs. However, influence of dosing time of day on
      effects of high molecular weight formulations, such as drugs encapsulated in
      liposomes, has not been studied in detail. This study demonstrates that blood
      pressure rhythm affects dosing time-dependent variation in effects of high
      molecular weight formulations. Systolic blood pressure in sarcoma 180-bearing
      mice showed significant 24-h oscillation. Intratumoral accumulation of
      fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA), an indicator
      of tumor vascular permeability, varied with dosing time of day, matching phases
      of blood pressure circadian rhythm. Furthermore, intratumoral accumulation of
      liposome-encapsulated oxaliplatin (Lipo-L-OHP) increased with increases in
      systolic blood pressure. Our findings suggest that circadian blood pressure
      oscillations may be an important factor to consider in dosing strategies for
      macromolecular drugs and liposomes in cancer therapy.

PMID- 29470988
TI  - Shear-dependent fibrillogenesis of fibronectin: Impact of platelet integrins and
      actin cytoskeleton.
AB  - Soluble plasma fibronectin (Fn) with its inactive compact structure requires
      unfolding to assemble into active fibrils, which play a role in hemostasis and
      thrombosis. Fn fibril assembly involves Fn binding to cell receptors,
      biomechanical coupling of Fn to the cytoskeleton by integrins, exposure of self
      assembly sites via contractile cell forces, and elongation of fibrils by Fn
      polymerization. In this report, we investigated the effect of platelet integrins
      and actin cytoskeleton on conformational changes of Fn induced by shear. Plasma
      Fn, in the presence or absence of washed platelets, was exposed to dynamic shear
      simulating venous or arterial flow conditions. Platelet integrins (alphaIIbbeta3,
      alphavbeta3, and alpha5beta1) were blocked by inhibitory antibodies to determine
      their contribution to shear-induced Fn fibrillogenesis. To examine the role of
      platelet cytoskeleton in Fn fibrillogenesis induced by shear, platelets were
      preincubated with cytoskeleton drugs, i. e jasplakinolide to stabilize actin or
      cytochalasin D to inhibit actin polymerization. Microscopic analyses demonstrated
      that flow and resulting shear stress over a broad range of physiological and
      pathological rates (50-5000 s-1) could induce conformational changes of plasma
      Fn. In addition, the formation of Fn fibrils is modulated by platelet integrins.
      In this respect, beta3 integrins play a dominant role in terms of Fn
      fibrillogenesis induced by shear. Disruption of the actin polymerization markedly
      diminished Fn unfolding and assembly. These observations lead to the conclusion
      that Fn-integrin beta3-cytoskeleton interaction is crucial for the assembly of
      plasma Fn matrix under flow conditions.

PMID- 29470989
TI  - Redox exchange of the disulfides of human two-domain CD4 regulates the
      conformational dynamics of each domain, providing insight into its mechanisms of
      control.
AB  - CD4, a membrane glycoprotein expressed by specific leukocytes, plays a vital role
      in the human immune response and acts as a primary receptor for HIV entry. Of its
      four ecto-domains (D1-D4), D1, D2, and D4 each contain a distinctive disulfide
      bond. Whereas the disulfides of D1 and D4 are more traditional in nature,
      providing structural functions, that of D2 is referred to as an "allosteric"
      disulfide due to its high dihedral strain energy and relative ease of reduction
      that is thought to regulate CD4 structure and function by shuffling its redox
      state. While we have shown previously that elimination of the pre-stressed D2
      disulfide results in a favorable structural collapse that increases the stability
      of a CD4 variant comprising only D1 and D2 (2dCD4), we sought to further localize
      and determine the nature of the biophysical modifications that take place upon
      redox exchange of the D1 and D2 disulfides by using amide hydrogen-deuterium
      exchange mass spectrometry (HDX-MS) to measure induced changes in conformational
      dynamics. By analyzing various redox isomers of 2dCD4, we demonstrate that
      ablation of the D1 disulfide enhances the dynamics of the domain considerably,
      with little effect on that of D2. Reduction of the D2 disulfide however decreases
      the conformational dynamics of many of the beta-strands of the domain that
      enclose the bond, suggesting a model in which inward collapse of secondary
      structure occurs around the allosteric disulfide upon its eradication, resulting
      in a marked decrease in hydrodynamic volume and increase in stability as
      previously described. Increases in the dynamics of regions important for HIV
      gp120 and MHCII binding in D1 also result allosterically after reducing the D2
      disulfide, which are likely a consequence of the structural changes that take
      place in D2, findings that advance our understanding of the mechanisms by which
      redox exchange of the CD4 disulfides regulates its function.

PMID- 29470991
TI  - Modeling factors that regulate cell cooperativity in the zebrafish posterior
      lateral line primordium.
AB  - Collective cell migration is an integral part of organismal development. We
      consider migration of the zebrafish primordium during development of the
      posterior lateral line, a sensory system that detects water movement patterns.
      Experiments have shown that the chemokine ligand CXCL12a and its receptors CXCR4b
      and CXCR7b are key players for driving migration of the primordium, while FGF
      signaling helps maintain cohesion. In this work, we formulate a mathematical
      model of a laser ablated primordium separated into two smaller cell collectives:
      a leading collective that responds to local CXCL12a levels and a trailing
      collective that migrates up a local FGF gradient. Our model replicates recent
      experimental results, while also predicting a "runaway" behavior when FGF
      gradient response is inhibited. We also use our model to estimate diffusion
      coefficients of CXCL12a and FGF in the lateral line.

PMID- 29470990
TI  - Lis1 dysfunction leads to traction force reduction and cytoskeletal
      disorganization during cell migration.
AB  - Cell migration is a critical process during development, tissue repair, and
      cancer metastasis. It requires complex processes of cell adhesion, cytoskeletal
      dynamics, and force generation. Lis1 plays an important role in the migration of
      neurons, fibroblasts and other cell types, and is essential for normal
      development of the cerebral cortex. Mutations in human LIS1 gene cause classical
      lissencephaly (smooth brain), resulting from defects in neuronal migration.
      However, how Lis1 may affect force generation in migrating cells is still not
      fully understood. Using traction force microscopy (TFM) with live cell imaging to
      measure cellular traction force in migrating NIH3T3 cells, we showed that Lis1
      knockdown (KD) by RNA interference (RNAi) caused reductions in cell migration and
      traction force against the extracellular matrix (ECM). Immunostaining of
      cytoskeletal components in Lis1 KD cells showed disorganization of microtubules
      and actin filaments. Interestingly, focal adhesions at the cell periphery were
      significantly reduced. These results suggest that Lis1 is important for cellular
      traction force generation through the regulation of cytoskeleton organization and
      focal adhesion formation in migrating cells.

PMID- 29470992
TI  - Control of cell fraction and population recovery during tissue regeneration in
      stem cell lineages.
AB  - Multicellular tissues are continually turning over, and homeostasis is maintained
      through regulated proliferation and differentiation of stem cells and
      progenitors. Following tissue injury, a dramatic increase in cell proliferation
      is commonly observed, resulting in rapid restoration of tissue size. This
      regulation is thought to occur via multiple feedback loops acting on cell self
      renewal or differentiation. Models of ordinary differential equations have been
      widely used to study the cell lineage system. Prior modeling studies have
      suggested that loss of homeostasis and initiation of tumorigenesis can be
      contributed to the loss of control of these processes, and the rate of symmetric
      versus asymmetric division of the stem cells may also be altered. While most of
      the previous works focused on analysis of stability, existence and uniqueness of
      steady states of multistage cell lineage models, in this work we attempt to
      understand the cell lineage model from a different perspective. We compare three
      variants of hierarchical stem cell lineage tissue models with different
      combinations of negative feedbacks and use sensitivity analysis to examine the
      possible strategies for the cells to achieve certain performance objectives. Our
      results suggest that multiple negative feedback loops must be present in the stem
      cell lineage to keep the fractions of stem cells to differentiated cells in the
      total population as robust as possible to variations in cell division parameters,
      and to minimize the time for tissue recovery in a non-oscillatory manner.

PMID- 29470993
TI  - Stress: Common themes toward the next frontier.
AB  - "Stress is complicated". A phrase uttered by many a stress researcher. This is
      true, from the vast array of stimuli considered "stressors" to the interactive
      and hormetic nature of the molecular, cellular, endocrine, and behavioral
      responses generated by such stressors. This commentary takes the position that
      stress researchers are poised to make even bigger contributions if they begin to
      shift from investigating the myriad effects of stress on brain and body, and to
      refocus a larger part of our efforts on more in-depth investigations of common
      themes in stress biology, with the goal of uncovering potential "universal
      principles" of stress that may help us better interpret the findings at higher
      levels of analysis, and provide a structured approach to help breach the next
      frontiers of stress research.

PMID- 29470994
TI  - A virus-like particle vaccine protects mice against coxsackievirus A10 lethal
      infection.
AB  - Coxsackievirus A10 (CVA10) has emerged worldwide as one of the main pathogens of
      hand, foot, and mouth disease (HFMD) in recent years. However, there is currently
      no commercial vaccine available to prevent CVA10 infection. Here we report the
      development of a recombinant virus-like particle (VLP) based candidate vaccine
      for CVA10. Co-expression of the capsid protein precursor P1 and the protease 3CD
      of CVA10 in Pichia pastoris resulted in cleavage of P1 into three capsid subunit
      proteins VP0, VP1, and VP3. These three subunit proteins co-assembled into CVA10
      VLPs, which were visualized as spherical particles with a diameter of ~30 nm
      under electron microscope. Immunization studies showed that CVA10 VLP could
      efficiently induce antigen-specific serum antibodies in mice. The anti-VLP sera
      were able to potently neutralize homologous and heterologous CVA10 strains.
      Importantly, passively transferred anti-VLP sera fully protected recipient
      neonatal mice from lethal CVA10 infection. In addition, neonatal mice born to the
      VLP-immunized dams were also completely protected from CVA10 lethal challenge.
      Collectively, these data show that CVA10 VLP represents a promising CVA10 vaccine
      candidate.

PMID- 29470995
TI  - RACK1/TRAF2 regulation of modulator of apoptosis-1 (MOAP-1).
AB  - MOAP-1 is a pro-apoptotic tumor suppressor molecule with a growing set of known
      interacting partners. We have demonstrated that during death receptor-dependent
      apoptosis, MOAP-1 is recruited to TNF-R1 or TRAIL-R1, followed by RASSF1A and Bax
      association. MOAP-1/Bax association promotes Bax conformational change resulting
      in the translocation of Bax into the mitochondrial membrane, mitochondrial
      membrane insertion and dysregulation resulting in several hallmark events that
      execute apoptosis. Although a role in apoptosis is established, it is currently
      unknown how MOAP-1 is regulated and how it links to Bax to promote apoptosis. In
      this study, we demonstrate robust association with RACK1, a versatile scaffolding
      protein that responds to activation of protein kinase C. Furthermore, we can
      demonstrate that RACK1 functions to bring the E3 ligase, TRAF2, to MOAP-1 in
      order to undergo a K63-dependent ubiquitination. Furthermore, RACK1 associates
      with MOAP-1 via electrostatic associations similar to those observed between MOAP
      1/RASSF1A and MOAP-1/TNF-R1. These events illustrate the complex nature of MOAP-1
      regulation and characterizes the important role of the scaffolding protein,
      RACK1, in influencing MOAP-1 biology.

PMID- 29470996
TI  - Default-mode network and deep gray-matter analysis in neuromyelitis optica
      patients.
AB  - OBJECTIVE: The aim of our study was to detect functional changes in default-mode
      network of neuromyelitis optica (NMO) patients using resting-state functional
      magnetic resonance images and the evaluation of subcortical gray-matter
      structures volumes. MATERIALS AND METHODS: NMO patients (n=28) and controls
      patients (n=19) were enrolled. We used the integrated registration and
      segmentation tool, part of FMRIB's Software Library (FSL) to segment subcortical
      structures including the thalamus, caudate nucleus, putamen, hippocampus and
      amygdalae. Resting-state functional magnetic resonance images were post-processed
      using the Multivariate Exploratory Linear Optimized Decomposition into
      Independent Components, also part of FSL. Average Z-values extracted from the
      default-mode network were compared between patients and controls using t-tests (P
      values <0.05 were considered statistically significant). RESULTS: There were
      areas of increased synchronization in the default-mode network of patients
      compared to controls, notably in the precuneus and right hippocampus (corrected
      P<0.01). The frontal area had decreased synchronization in patients compared to
      controls (corrected P<0.01). There were no observed differences between patients
      and controls in subcortical volumes or average Z-values values for default-mode
      network. CONCLUSION: The hyperactivity of certain default-mode network areas may
      reflect cortical compensation for subtle structural damage in NMO patients.

PMID- 29470997
TI  - Predictors of favorable outcome after mechanical thrombectomy for anterior
      circulation acute ischemic stroke in octogenarians.
AB  - INTRODUCTION: Mechanical thrombectomy for anterior circulation large vessel
      occlusion (LVO) improves functional outcome at three months. This therapeutic
      approach is the new gold standard, with a benefit being also observed in elderly
      patients. However, data are limited in this heterogeneous and fragile population.
      The objectives of this study were, first, to describe outcome after mechanical
      thrombectomy in a representative group of patients over 80. Second, to evaluate
      factors associated with a favorable functional outcome after thrombectomy for
      anterior circulation LVO in elderly patients (aged>=80 years). METHODS: A total
      of 169 patients with anterior circulation LVO referred for an endovascular
      treatment were included. Primary outcome evaluated functional outcome at three
      months. Multivariable analysis was performed to identify prognostic factors in
      elderly patients with pre-stroke mRS<=3. RESULTS: Overall, 25.34% of patients
      (43/169) were functionally independent at three months (mRS<=2) and 16.57%
      (28/169) had a moderate functional disability (mRS=3). Mortality rate was 33.14%
      (56/169). At 24h, 7.1% of patients (12/169) had symptomatic hemorrhage. Male
      gender (P=0.033), low initial NIHSS (P=0.037), higher DWI-ASPECTS (P=0.022) and
      use of intravenous thrombolysis (IVT) (P=0.0193) were associated with a better
      functional outcome. CONCLUSIONS: There is no reason to withhold mechanical
      thrombectomy on the basis of age alone. Small infarct core, low NIHSS, male
      gender and use of IVT are associated with a better functional outcome.

PMID- 29470998
TI  - Evaluation of a New Design of Antireflux-biodegradable Ureteral Stent in Animal
      Model.
AB  - OBJECTIVE: To determine the effects in urinary tract of a new antireflux
      biodegradable ureteral stent. MATERIALS AND METHODS: Thirty six ureters belonging
      to 24 pigs were used. The study began with endoscopic, nephrosonographic, and
      fluoroscopic assessments. Three study groups of ureters (n = 12) were then
      specified. In group I, a biodegradable antireflux ureteral stent (BDG-ARS) was
      inserted in the right ureter of 12 pigs. Group II comprised the left ureter of
      the same animals, in which a double-pigtail stent was placed for 6 weeks. Group
      III ureters, belonging to 12 additional animals, were subjected to a
      ureteropelvic junction obstruction model that was then treated by endopyelotomy
      and stenting with BDG-ARS. Follow-ups were performed at 3-6 weeks and at 5
      months. RESULTS: None of the ureters receiving the BDG-ARS showed any evidence of
      vesicoureteral reflux (VUR). BDG-ARS degradation took place in a controlled and
      predictable fashion from the third to the sixth weeks, and no obstructive
      fragments appeared. No differences were found between groups I and II regarding
      passive ureteral dilation, but significant differences were found regarding VUR
      and ureteral orifice damage. BDG-ARS always maintained distal ureteral
      peristalsis. BDG-ARS in group III showed a 50% positive urine culture rate and a
      16.6% migration rate in both BDG-ARS groups. CONCLUSION: BDG-ARS avoided VUR and
      bladder trigone irritation. In addition, this polymer combination and stent
      braided design achieved a consistent biodegradation rate with no obstructive
      fragments and with uniform degradation between the third and the sixth weeks.
      Consequently, morbidity associated with ureteral stents might be reduced.

PMID- 29470999
TI  - Mast cells regulate CD4+ T-cell differentiation in the absence of antigen
      presentation.
AB  - BACKGROUND: Given their unique capacity for antigen uptake, processing, and
      presentation, antigen-presenting cells (APCs) are critical for initiating and
      regulating innate and adaptive immune responses. We have previously shown the
      role of nicotinamide adenine dinucleotide (NAD+) in T-cell differentiation
      independently of the cytokine milieu, whereas the precise mechanisms remained
      unknown. OBJECTIVE: The objective of this study is to further dissect the
      mechanism of actions of NAD+ and determine the effect of APCs on NAD+-mediated T
      cell activation. METHODS: Isolated dendritic cells and bone marrow-derived mast
      cells (MCs) were used to characterize the mechanisms of action of NAD+ on CD4+ T
      cell fate in vitro. Furthermore, NAD+-mediated CD4+ T-cell differentiation was
      investigated in vivo by using wild-type C57BL/6, MC-/-, MHC class II-/-, Wiskott
      Aldrich syndrome protein (WASP)-/-, 5C.C7 recombination-activating gene 2 (Rag2)
      /-, and CD11b-DTR transgenic mice. Finally, we tested the physiologic effect of
      NAD+ on the systemic immune response in the context of Listeria monocytogenes
      infection. RESULTS: Our in vivo and in vitro findings indicate that after NAD+
      administration, MCs exclusively promote CD4+ T-cell differentiation, both in the
      absence of antigen and independently of major APCs. Moreover, we found that MCs
      mediated CD4+ T-cell differentiation independently of MHC II and T-cell receptor
      signaling machinery. More importantly, although treatment with NAD+ resulted in
      decreased MHC II expression on CD11c+ cells, MC-mediated CD4+ T-cell
      differentiation rendered mice resistant to administration of lethal doses of L
      monocytogenes. CONCLUSIONS: Collectively, our study unravels a novel cellular and
      molecular pathway that regulates innate and adaptive immunity through MCs
      exclusively and underscores the therapeutic potential of NAD+ in the context of
      primary immunodeficiencies and antimicrobial resistance.

PMID- 29471000
TI  - Relationship between cerebrospinal fluid concentrations of orexin A/hypocretin-1
      and body composition in humans.
AB  - The hypothalamic neuropeptide orexin A (hypocretin-1) is a key signal in
      sleep/wake regulation and promotes food intake. We investigated the relationship
      between cerebrospinal fluid orexin A concentrations and body composition in non
      narcoleptic human subjects with a wide range of body weight to gain insight into
      the role of orexin A in human metabolism. We collected cerebrospinal fluid and
      blood samples and measured body composition by bioelectric impedance analysis in
      36 subjects (16 women and 20 men) with body mass indices between 16.24 and 38.10
      kg/m2 and an age range of 19-80 years. Bivariate Pearson correlations and
      stepwise multiple regressions were calculated to determine associations between
      orexin A and body composition as well as biometric variables. Concentrations of
      orexin A in cerebrospinal fluid averaged 315.6 +/- 6.0 pg/ml, were comparable
      between sexes (p > 0.15) and unrelated to age (p > 0.66); they appeared slightly
      reduced in overweight/obese compared to normal-weight subjects (p = .07). Orexin
      A concentrations decreased with body weight (r = -0.38, p = .0229) and fat-free
      mass (r = -0.39, p = .0173) but were not linked to body fat mass (p > 0.24). They
      were inversely related to total body water (r = -0.39, p = .0174) as well as
      intracellular (r = -0.41, p = .0139) and extracellular water (r = -0.35, p =
      .0341). Intracellular water was the only factor independently associated with
      cerebrospinal fluid orexin A concentrations (p = .0139). We conclude that
      cerebrospinal fluid orexin A concentrations do not display associations with body
      adiposity, but are inversely related to intracellular water content. These cross
      sectional findings suggest a link between orexin A signaling and the regulation
      of water homeostasis in humans.

PMID- 29471001
TI  - Activated CXCL5-CXCR2 axis promotes the migration, invasion and EMT of papillary
      thyroid carcinoma cells via modulation of beta-catenin pathway.
AB  - Initiation of epithelial-to-mesenchymal transition (EMT) is common in papillary
      thyroid carcinoma (PTC) and may contribute to its metastasis. Aims of the present
      study are to investigate whether and how the C-X-C motif chemokine ligand (CXCL)
      5/C-X-C motif receptor 2 (CXCR2) axis affects PTC metastasis, with a focus on the
      EMT process. Herein, two PTC cell lines, KTC-1 and B-CPAP cells, identified as
      CXCR2-positive cells were used as the cell model. We found that a 24-h
      stimulation of 1 or 10 nM recombinant human CXCL5 (rhCXCL5) enhanced the
      migration and invasion of both KTC-1 and B-CPAP cells without affecting their
      proliferation. The migration- and invasion-promoting effects of rhCXCL5 were
      attenuated if CXCR2 was silenced by its specific short hairpin RNAs (shRNAs). EMT
      initiation is defined as downregulation of epithelial-cadherin (E-cadherin) and
      upregulation of N-cadherin, Vimentin and Snail. Our data showed that rhCXCL5
      induced EMT in PTC cells was suppressed by CXCR2 shRNA. Furthermore, the active
      CXCL5-CXCR2 axis enhanced the phosphorylation of Akt at Ser 473 residue and that
      of glycogen synthase kinase-3 (GSK-3beta) at Ser 9 residue, and accelerated the
      nuclear accumulation of beta-catenin in PTC cells. Re-expression of the active
      form of beta-catenin in PTC cells rescued their impaired invasiveness caused by
      the blockade of CXCL5-CXCR2 axis. In addition, CXCL5 and CXCR2 were overexpressed
      in the metastatic lymph nodes obtained from 18 patients with PTC. In summary, our
      study demonstrates that the activated CXCL5-CXCR2 axis contributes to the
      metastatic phenotype of PTC cells by modulating Akt/GSK-3beta/beta-catenin
      pathway.

PMID- 29471002
TI  - Interpersonal relationship modulates the behavioral and neural responses during
      moral decision-making.
AB  - Interpersonal relationship (IR) may play an important role in moral decision
      making. However, it is little known about how IR influences neural and behavioral
      responses during moral decision-making. The present study utilized the dilemma
      scenario-priming paradigm to examine the time course of the different intimate IR
      (friend, acquaintance, or stranger) impacts on the emotional and cognitive
      processes during moral decision-making. Results showed that participants made
      less altruistic decisions with increased decision times and experienced more
      unpleasure for strangers versus friends and acquaintances. Moreover, at the early
      moral intuitional process, there was no significance difference observed at N1
      under different intimate IR; however, at the emotional process, larger P260 which
      reflects the dilemma conflicts and negative emotional responses, was elicited
      when moral decision-making for strangers; at the later cognitive process, such
      difference was also observed at LPP (300-450 ms) which indexes the later top-down
      cognitive appraisal and reasoning processes. However, such differences were not
      observed between friends and acquaintances. Results indicate that IR modulates
      the emotional and cognitive processes during moral decision-making, suggesting
      that the closer the IR is, the weaker the dilemma conflicts and emotional
      responses are, and the more efficient this conflicts are solved.

PMID- 29471003
TI  - TrkB receptor antagonism inhibits stab injury induced proliferative response in
      adult zebrafish (Danio rerio) brain.
AB  - The Tropomyosin related kinase B (TrkB) receptor, is known to promote neuronal
      maturation, differentiation, maintenance and survival through its cognate ligands
      Brain derived neurotrophic factor (BDNF) and neurotrophin 4 (NT4). BDNF, NT4 and
      TrkB are highly conserved proteins among vertebrates. Although the role of TrkB
      during brain development is well established, its role in adult neurogenesis and
      brain regeneration awaits thorough investigation. In this study, we used the
      zebrafish stab wound injury model to determine whether the injury induced
      regeneration response in the telencephalon region is governed by TrkB or not. We
      induced stab wound injury in the mid-dorsal region of telencephalon of ANA-12
      (selective TrkB antagonist) treated and non-treated zebrafish brain and examined
      the proliferation activity in selected brain regions using immunohistochemistry.
      We found that proliferation activity was significantly low in ANA-12 injected
      injured fishes as compared to vehicle control injured fishes. Other major
      findings of the study include the temporal pattern of proliferation activity
      after an injury and activation of adult neural stem cells (aNSCs) situated
      distantly apart from the injury site in the adult zebrafish brain.

PMID- 29471005
TI  - MiR-155-5p controls colon cancer cell migration via post-transcriptional
      regulation of Human Antigen R (HuR).
AB  - Colorectal cancer (CRC) is the third most common cancer and a significant cause
      of cancer-related deaths worldwide. Metastasis is the worst prognostic factor for
      patients with CRC. HuR (ELAVL1) is overexpressed in CRC and has been reported to
      promote colon cancer growth by targeting RNA in the cell cytoplasm. Herein, the
      role of miR-155-5p in regulating HuR expression and cell migration was examined
      in colon cancer cells. MiR-155-5p knockdown in serum-starved colon cancer cells
      decreased both colon cancer cell chemotaxis and cytoplasmic expression of HuR.
      Bioinformatics analysis predicted two putative binding sites in the AU-rich
      elements (AREs) at the 3'-UTR of HuR mRNA. MiR-155-5p binding to HuR was verified
      using specific target site blockers and functionally validated by use of RNA
      immunoprecipitation assays, showing that miR-155-5p-dependent regulation of HuR
      expression is mediated by AREs. Targeting AREs with a specific blocker inhibited
      colon cancer cell migration. Taken together, these novel findings demonstrate
      that AREs mediate miR-155-5p positive regulation of HuR mRNA levels and
      translation as well as migration in colon cancer cells, suggesting that targeting
      miR-155-5p and/or Hur might be useful therapeutic strategies against colon cancer
      metastasis.

PMID- 29471004
TI  - Prostate cancer chemoprevention by natural agents: Clinical evidence and
      potential implications.
AB  - Prostate cancer (PCa) is the most common non-skin cancer and the second leading
      cause of cancer-related deaths in American men. Due to its long latency period,
      PCa is considered as an ideal cancer type for chemopreventive interventions.
      Chemopreventive agents include various natural or synthetic agents that prevent
      or delay cancer development, progression and/or recurrence. Pre-clinical studies
      suggest that many natural products and dietary agents have chemopreventive
      properties. However, a limited number of these agents have been tested in
      clinical trials, with varying success. In this review, we have discussed the
      available clinical studies regarding the efficacy of natural chemopreventive
      agents against PCa, including tea polyphenols, selenium, soy proteins, vitamins
      and resveratrol. We have also provided a discussion on the clinical challenges
      and opportunities for the potential use of chemopreventive agents against PCa.
      Based on available literature, it appears that the variable outcomes of the
      chemopreventive clinical studies necessitate a need for additional studies with
      more rigorous designs and methodical interpretations in order to measure the
      potential of the natural agents against PCa.

PMID- 29471006
TI  - Astilbin ameliorates cisplatin-induced nephrotoxicity through reducing oxidative
      stress and inflammation.
AB  - Oxidative stress and inflammation are considered to be the main pathogenesis of
      cisplatin nephrotoxicity. Astilbin, a flavonoid with anti-oxidation and anti
      inflammation function, has been used to treat heavy metal induced kidney injury.
      In this study, we investigated the protective effects of astilbin on cisplatin
      induced nephrotoxicity and its underlying mechanisms. Our results showed that
      astilbin markedly inhibited cisplatin-induced cell apoptosis and recovered cell
      growth. Astilbin significantly decreased reactive oxygen species (ROS)
      accumulation and alleviated ROS-induced activation of p53, MAPKs and AKT
      signaling cascades, which in turn attenuated cisplatin-induced HEK-293 cell
      apoptosis. Astilbin effectively enhanced NRF2 activation and transcription of its
      targeting antioxidant genes to reduce ROS accumulation in cisplatin-induced HEK
      293 cells. Furthermore, we found that astilbin obviously suppressed tumor
      necrosis factor alpha (TNF-alpha) expression and NF-kappaB activation, and also
      inhibited the expression of induced nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2). Finally, we confirmed that the effect of astilbin to
      improve renal oxidative stress and inflammation in cisplatin induced acute
      nephrotoxic mice. In conclusion, our study suggests that astilbin could
      ameliorate the cisplatin-induced nephrotoxicity by reducing oxidative stress and
      inflammation.

PMID- 29471007
TI  - Risk assessment of benzene in food samples of Iran's market.
AB  - The concentration of benzene in ninety-eight collected food and drink samples
      (carbonated beverage, fruit juice, pickle, lime juice, mayonnaise and salad
      dressing, 16 samples from each) from Iran local markets were investigated using
      gas chromatography equipped with flame ionization detector (GC-FID). Moreover,
      the correlation of benzene concentration with sodium benzoate and ascorbic acid
      concentrations was assessed. Benzene concentration in carbonated beverages, fruit
      juices, pickle, lime juices, mayonnaise and salad dressing were 3.57 +/- 1.70,
      5.17 +/- 3.63, 4.37 +/- 2.24, 4.99 +/- 0.54, 1.38 +/- 0.87 and 1.47 +/- 0.83
      MUg/L, respectively, being in all cases below the acceptable limit (10 MUg/L)
      proposed by the World Health Organization (WHO) as a reference for drinking
      water. Benzene concentration exceeded the maximum tolerable limit in 12.5% of
      carbonated beverages and fruit juices (two samples from each). A significant
      correlation coefficient between the concentrations of benzene, sodium benzoate,
      and ascorbic acid in fruit juices, and levels of benzene, sodium benzoate in
      carbonated beverage samples was observed. To characterize the risk of exposure of
      urban and rural consumers of Iran (female in age group of 15-24 and male in age
      group of 25-64) to benzene in food and drink samples the Margin of Exposure (MoE)
      approach was applied revealing there is no severe concern regarding benzene
      intake through assessed food and beverages samples in Iran.

PMID- 29471008
TI  - The chain of survival: Not all links are equal.
AB  - The chain of survival aims to demonstrate the interrelationship between key
      stages of resuscitation and emphasises the need for all links to be effective in
      order to optimise the chances of survival. The contribution of each of the four
      links diminishes rapidly as patients succumb at each stage and the actual
      attrition rate results in rapidly decreasing numbers of patients progressing
      along the chain. This revised representation adjusts the area of each link in
      order to graphically represent the flow of patients through the chain. Greatest
      benefit in improving outcome will be achieved by focussing on improving care at
      links in the chain where there is the greatest number of patients.

PMID- 29471009
TI  - Patterns induced by super cross-diffusion in a predator-prey system with
      Michaelis-Menten type harvesting.
AB  - Turing instability and pattern formation in a super cross-diffusion predator-prey
      system with Michaelis-Menten type predator harvesting are investigated. Stability
      of equilibrium points is first explored with or without super cross-diffusion. It
      is found that cross-diffusion could induce instability of equilibria. To further
      derive the conditions of Turing instability, the linear stability analysis is
      carried out. From theoretical analysis, note that cross-diffusion is the key
      mechanism for the formation of spatial patterns. By taking cross-diffusion rate
      as bifurcation parameter, we derive amplitude equations near the Turing
      bifurcation point for the excited modes by means of weakly nonlinear theory.
      Dynamical analysis of the amplitude equations interprets the structural
      transitions and stability of various forms of Turing patterns. Furthermore, the
      theoretical results are illustrated via numerical simulations.

PMID- 29471010
TI  - Phylogenetic diversity and biodiversity indices on phylogenetic networks.
AB  - In biodiversity conservation it is often necessary to prioritize the species to
      conserve. Existing approaches to prioritization, e.g. the Fair Proportion Index
      and the Shapley Value, are based on phylogenetic trees and rank species according
      to their contribution to overall phylogenetic diversity. However, in many cases
      evolution is not treelike and thus, phylogenetic networks have been developed as
      a generalization of phylogenetic trees, allowing for the representation of non
      treelike evolutionary events, such as hybridization. Here, we extend the concepts
      of phylogenetic diversity and phylogenetic diversity indices from phylogenetic
      trees to phylogenetic networks. On the one hand, we consider the treelike content
      of a phylogenetic network, e.g. the (multi)set of phylogenetic trees displayed by
      a network and the so-called lowest stable ancestor tree associated with it. On
      the other hand, we derive the phylogenetic diversity of subsets of taxa and
      biodiversity indices directly from the internal structure of the network. We
      consider both approaches that are independent of so-called inheritance
      probabilities as well as approaches that explicitly incorporate these
      probabilities. Furthermore, we introduce our software package NetDiversity, which
      is implemented in Perl and allows for the calculation of all generalized measures
      of phylogenetic diversity and generalized phylogenetic diversity indices
      established in this note that are independent of inheritance probabilities. We
      apply our methods to a phylogenetic network representing the evolutionary
      relationships among swordtails and platyfishes (Xiphophorus: Poeciliidae), a
      group of species characterized by widespread hybridization.

PMID- 29471011
TI  - Gaussian process approximations for fast inference from infectious disease data.
AB  - We present a flexible framework for deriving and quantifying the accuracy of
      Gaussian process approximations to non-linear stochastic individual-based models
      of epidemics. We develop this for the SIR and SEIR models, and we show how it can
      be used to perform quick maximum likelihood inference for the underlying
      parameters given population estimates of the number of infecteds or cases at
      given time points. We also show how the unobserved processes can be inferred at
      the same time as the underlying parameters.

PMID- 29471012
TI  - Paediatric fatty liver disease (PeFLD): All is not NAFLD - Pathophysiological
      insights and approach to management.
AB  - The recognition of a pattern of steatotic liver injury where histology mimicked
      alcoholic liver disease, but alcohol consumption was denied, led to the
      identification of non-alcoholic fatty liver disease (NAFLD). Non-alcoholic fatty
      liver disease has since become the most common chronic liver disease in adults
      owing to the global epidemic of obesity. However, in paediatrics, the term NAFLD
      seems incongruous: alcohol consumption is largely not a factor and inherited
      metabolic disorders can mimic or co-exist with a diagnosis of NAFLD. The term
      paediatric fatty liver disease may be more appropriate. In this article, we
      summarise the known causes of steatosis in children according to their typical,
      clinical presentation: i) acute liver failure; ii) neonatal or infantile
      jaundice; iii) hepatomegaly, splenomegaly or hepatosplenomegaly; iv)
      developmental delay/psychomotor retardation and perhaps most commonly; v) the
      asymptomatic child with incidental discovery of abnormal liver enzymes. We offer
      this model as a means to provide pathophysiological insights and an approach to
      management of the ever more complex subject of fatty liver.

PMID- 29471013
TI  - Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs.
      sorafenib for advanced hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: To compare the overall survival (OS) and disease progression
      free survival (PFS) in patients with advanced hepatocellular carcinoma (Ad-HCC)
      who are undergoing hepatic arterial infusion (HAI) of oxaliplatin,
      fluorouracil/leucovorin (FOLFOX) treatment vs. sorafenib. METHODS: This
      retrospective study was approved by the ethical review committee, and informed
      consent was obtained from all patients before treatment. HAI of FOLFOX (HAIF) was
      recommended as an alternative treatment option for patients who refused
      sorafenib. Of the 412 patients with Ad-HCC (376 men and 36 women) between Jan
      2012 to Dec 2015, 232 patients were treated with sorafenib; 180 patients were
      given HAIF therapy. The median age was 51 years (range, 16-82 years). Propensity
      score matched estimates were used to reduce bias when evaluating survival.
      Survival curves were calculated by performing the Kaplan-Meier method and
      compared by using the log-rank test and Cox regression models. RESULTS: The
      median PFS and OS in the HAIF group were significantly longer than those in the
      sorafenib group (PFS 7.1 vs. 3.3 months [RECIST]/7.4 vs. 3.6 months [mRECIST],
      respectively; OS 14.5 vs. 7.0 months; p <0.001 for each). In the propensity-score
      matched cohorts (147 pairs), both PFS and OS in the HAIF group were longer than
      those in the sorafenib group (p <0.001). At multivariate analysis, HAIF treatment
      was an independent factor for PFS (hazard ratio [HR] 0.389 [RECIST]/0.402
      [mRECIST]; p <0.001 for each) and OS (HR 0.129; p <0.001). CONCLUSION: HAIF
      therapy may improve survival compared to sorafenib in patients with Ad-HCC. A
      prospective randomized trial is ongoing to confirm this finding. LAY SUMMARY: We
      compared the hepatic arterial infusion of FOLFOX (a combination chemotherapy)
      with sorafenib (a tyrosine kinase inhibitor) in patients with advanced
      hepatocellular carcinoma, retrospectively. It was found that hepatic arterial
      infusion of FOLFOX therapy may improve both progression free and overall survival
      in patients with advanced hepatocellular carcinoma.

PMID- 29471014
TI  - Epigenomic drugs and the germline: Collateral damage in the home of heritability?
AB  - The testis and ovary provide specialised environments that nurture germ cells and
      facilitate their maturation, culminating in the production of mature gametes that
      can found the following generation. The sperm and egg not only transmit genetic
      information, but also epigenetic modifications that affect the development and
      physiology of offspring. Importantly, the epigenetic information contained in
      mature sperm and oocytes can be influenced by a range of environmental factors,
      such as diet, chemicals and drugs. An increasing range of studies are revealing
      how gene-environment interactions are mediated through the germline. Outside the
      germline, altered epigenetic state is common in a range of diseases, including
      many cancers. As epigenetic modifications are reversible, pharmaceuticals that
      directly target epigenetic modifying proteins have been developed and are
      delivering substantial benefits to patients, particularly in oncology. While
      providing the most effective patient treatment is clearly the primary concern,
      some patients will want to conceive children after treatment. However, the
      impacts of epigenomic drugs on the male and female gametes are poorly understood
      and whether these drugs will have lasting effects on patients' germline epigenome
      and subsequent offspring remains largely undetermined. Currently, evidence based
      clinical guidelines for use of epigenomic drugs in patients of reproductive age
      are limited in this context. Developing a deeper understanding of the epigenetic
      mechanisms regulating the germline epigenome and its impact on inherited traits
      and disease susceptibility is required to determine how specific epigenomic drugs
      might affect the germline and inheritance. Understanding these potential effects
      will facilitate the development of informed clinical guidelines appropriate for
      the use of epigenomic drugs in patients of reproductive age, ultimately improving
      the safety of these therapies in the clinic.

PMID- 29471015
TI  - Biological profiling of plasma neuropeptide Y in relation to posttraumatic stress
      symptoms in two combat cohorts.
AB  - In order to decrease the risk of developing stress-related disorders after
      military deployment, biological vulnerability factors should be identified.
      Neuropeptide Y (NPY) is a peptide neurotransmitter that is associated with
      modulation of the stress response. Using the data of two longitudinal prospective
      cohort studies (N = 892 and N = 2427), plasma NPY (pNPY) was assessed as a
      possible susceptibility biomarker for the development of PTSD symptoms over time.
      Data collection started prior to deployment and follow-up assessments were
      completed up to two years after deployment. In pNPY levels, measured before and
      shortly after deployment, three distinct trajectories were identified. In both
      cohorts, these trajectories were not related to the level of reported PTSD
      symptoms over time and neither were pre-deployment pNPY levels. Whereas previous
      research suggested that high NPY levels might be a marker for resilience, the
      current findings suggest limited usefulness of peripherally measured NPY in the
      development of PTSD.

PMID- 29471016
TI  - Sensitivity to psychosocial chronic stressors and adolescents' externalizing
      problems: Combined moderator effects of resting heart rate and parental
      psychiatric history.
AB  - From the literature it is not clear whether low resting heart rate (HR) reflects
      low or high sensitivity to the detrimental effects of adverse environments on
      externalizing problems. We studied parental psychiatric history (PH), reflecting
      general vulnerability, as possible moderator explaining these inconsistencies.
      Using Linear Mixed Models, we analyzed data from 1914 subjects, obtained in three
      measurement waves (mean age 11, 13.5, and 16 years) from the TRacking
      Adolescents' Individual Lives Survey population-based cohort and the parallel
      clinic-referred cohort. As hypothesized, more chronic stressors predicted more
      externalizing problems in vulnerable individuals with high resting HR but not in
      those with low resting HR, suggesting high vs. low sensitivity, respectively, to
      adverse environmental influences. Low sensitivity to adverse environmental
      influences in vulnerable individuals exposed to high stressor levels was
      additionally confirmed by high heart rate variability (Root Mean Squared
      Successive Difference; RMSSD). In adolescents with low vulnerability, in
      contrast, the association between chronic stressors and externalizing problems
      did not substantially differ by resting HR and RMSSD. Future research may
      demonstrate whether our findings extend to other adverse, or beneficial,
      influences. Notwithstanding their theoretical interest, the effects were small,
      only pertained to parent-reported externalizing problems, refer to a small subset
      of respondents in our sample, and are in need of replication. We conclude that HR
      and RMSSD are unlikely to be strong moderators of the association between
      stressors and externalizing problems.

PMID- 29471017
TI  - Moderate effects of noninvasive brain stimulation of the frontal cortex for
      improving negative symptoms in schizophrenia: Meta-analysis of controlled trials.
AB  - BACKGROUND: Negative symptoms in schizophrenia concern a clinically relevant
      reduction of goal-directed behavior that strongly and negatively impacts daily
      functioning. Existing treatments are of marginal effect and novel approaches are
      needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic
      stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel
      approaches that may hold promise. OBJECTIVES: To provide a quantitative
      integration of the published evidence regarding effects of rTMS and tDCS over the
      frontal cortex on negative symptoms, including an analysis of effects of sham
      stimulation. METHODS: Meta-analysis was applied, using a random effects model, to
      calculate mean weighted effect sizes (Cohen's d). Heterogeneity was assessed by
      using Cochrans Q and I2 tests. RESULTS: For rTMS treatment, the mean weighted
      effect size compared to sham stimulation was 0.64 (0.32-0.96; k = 22, total N =
      827). Studies with younger participants showed stronger effects as compared to
      studies with older participants. For tDCS studies a mean weighted effect size of
      0.50 (-0.07 to 1.07; k = 5, total N = 134) was found. For all frontal noninvasive
      neurostimulation studies together (i.e., TMS and tDCS studies combined) active
      stimulation was superior to sham, the mean weighted effect size was 0.61 (24
      studies, 27 comparisons, 95% confidence interval 0.33-0.89; total N = 961). Sham
      rTMS (baseline - posttreatment comparison) showed a significant improvement of
      negative symptoms, d = 0.31 (0.09-0.52; k = 16, total N = 333). Whereas previous
      meta-analyses were underpowered, our meta-analysis had a power of 0.87 to detect
      a small effect. CONCLUSIONS: The available evidence indicates that noninvasive
      prefrontal neurostimulation can improve negative symptoms. This finding suggests
      a causal role for the lateral frontal cortex in self-initiated goal-directed
      behavior. The evidence is stronger for rTMS than for tDCS, although this may be
      due to the small number of studies as yet with tDCS. More research is needed to
      establish moderator variables that may affect response to neurostimulation and to
      optimize treatment parameters in order to achieve stable and durable (and thus
      clinically relevant) effects.

PMID- 29471018
TI  - Rotenone induces gastrointestinal pathology and microbiota alterations in a rat
      model of Parkinson's disease.
AB  - While people are often aware of the motor symptoms in Parkinson's disease (PD),
      few know of the many non-motor symptoms, which patients report have a greater
      impact on their quality of life. Gastrointestinal (GI) dysfunction is one of the
      most common non-motor symptoms, which can occur at any stage of PD, even years
      prior to diagnosis, and can affect all sections along the GI tract causing a
      range of symptoms including drooling, gastroparesis and constipation. We have
      investigated whether a neurotoxin model of PD induced by rotenone, a
      mitochondrial complex I inhibitor, is capable of reproducing the GI dysfunction
      seen clinically. Sprague-Dawley rats were administered 2.75 mg/kg rotenone, 5
      days/week for 4 weeks, via intraperitoneal injection. Rats underwent behavioural
      testing, including the one-hour stool and gastric emptying tests before GI
      contents and tissues were collected for microbiota and histological analysis.
      Rats exposed to rotenone had more days with evidence of diarrhoea and
      significantly delayed gastric emptying, reproducing the clinical symptom of
      gastroparesis. Microbiota analysis revealed alterations in the small intestine
      and colon of rotenone-treated rats, relatively consistent with changes described
      in PD patients. Histological analysis demonstrated mucosal thickening and goblet
      cell hyperplasia in the colon of rotenone rats, which may be an adaptive response
      to the toxin or changes in GI microbiota. Our results indicate that rotenone may
      be a good model for investigating the mechanisms involved with Parkinson's GI
      symptoms and for screening potential therapeutic options as it is capable of
      recapitulating some key GI changes that occur during PD progression.

PMID- 29471020
TI  - Ezrin as a complementary marker in ocular toxicity assessment using a three
      dimensional reconstructed human corneal-like epithelium model, EpiOcularTM.
AB  - INTRODUCTION: A variety of in vitro tests to replace the Draize test have been
      developed; however, there is no available method for assessing the full spectrum
      of Globally Harmonized System (GHS) categories. Human cornea-like three
      dimensional (3D) reconstructed tissue models are the most promising in vitro
      systems. The objective of this study was to evaluate the ocular toxicity of 11
      test substances using the EpiOcularTM model after performing proficiency tests.
      We further evaluated the effectiveness of ezrin staining as a complementary
      marker in histological analysis to overcome the limitation of eye irritation
      tests using 3D reconstructed human corneal epithelium models. METHODS: The
      assessment of ocular toxicity was performed by the suggested OECD TG 492
      procedure. After treatment with proficiency test chemicals and 10 test
      substances, EpiOcularTM tissue models were stained with hematoxylin and eosin and
      ezrin, and the histological changes were observed by immunofluorescence
      microscopy. RESULTS: The ocular toxicity assessment of 10 test chemicals using
      the EpiOcularTM eye irritation test were in accordance with the UN GHS
      classification of test chemicals. Histological analysis of ezrin staining showed
      that the cell membranes of models treated with 10 out of 11 non-irritant
      chemicals were maintained, whereas those of models treated with 14 eye irritant
      substances resulted in the apparent translocation of ezrins from the cell
      membrane to the cytoplasm or nucleus by destruction of cell membrane. DISCUSSION:
      Ezrin may be used as a complementary marker to more accurately assess ocular
      toxicity using 3D reconstructed human cornea-like epithelium models.

PMID- 29471019
TI  - Hsp90 Co-chaperone p23 contributes to dopaminergic mitochondrial stress via
      stabilization of PHD2: Implications for Parkinson's disease.
AB  - The heat shock factor 90 (hsp90) complex has long been associated with
      neuropathological phenotypes linked to Parkinson's disease (PD) and its
      inhibition is neuroprotective in disease models. Hsp90 is conventionally believed
      to act by suppressing induction of hsp70. Here, we report a novel hsp70
      independent mechanism by which Hsp90 may also contribute to PD-associated
      neuropathology. We previously reported that inhibition of the enzyme prolyl
      hydroxylase domain 2 (PHD2) in conjunction with increases in hypoxia-inducible
      factor 1 alpha (HIF1alpha) results in protection of vulnerable dopaminergic
      substantia nigra pars compacta (DAergic SNpc) neurons in in vitro and in vivo
      models of PD. We discovered an increased interaction between PHD2 and the
      p23:Hsp90 chaperone complex in response to mitochondrial stress elicited by the
      mitochondrial neurotoxin 1-methyl-4-phenylpyridine (MPP+) within cultured DAergic
      cells. Genetic p23 knockdown was found to result in decreases in steady-state
      PHD2 protein and activity and reduced susceptibility to MPP+ neurotoxicity.
      Administration of the p23 inhibitor gedunin was also neuroprotective in these
      cells as well as in human induced pluripotent stem cell (iPSC)-derived neurons.
      Our data suggests that mitochondrial stress-mediated elevations in PHD2
      interaction with the p23-hsp90 complex have detrimental effects on the survival
      of DAergic neurons, while p23 inhibition is neuroprotective. We propose that
      neurotoxic effects are tied to enhanced PHD2 stabilization by the hsp90-p23
      chaperone complex that is abrogated by p23 inhibition. This demonstrates a novel
      connection between two independent pathways previously linked to PD, hsp90 and
      PHD2-HIF1alpha, which could have important implications for here-to-fore
      unexplored mechanisms underlying PD neuropathology.

PMID- 29471022
TI  - Temporal lobe epilepsy-induced neurodegeneration and cognitive deficits:
      Implications for aging.
AB  - Epilepsy is a neurological condition associated with seizures, neurodegeneration,
      circuit reorganization, and other structural and functional abnormalities. These
      elements ultimately lead to behavioural alterations such as anxiety, depression,
      and importantly cognitive impairment like learning disability and memory
      impairment. These factors can attribute to acceleration of aging and cognitive
      impairment in middle-aged people, which is otherwise evident in dementia and
      Alzheimer's disease among elderly people. In addition to epilepsy per se, several
      studies have shown that conventional anti-epileptic drugs used to treat epilepsy
      also contributes to aging and cognitive deficits through their adverse effects.
      The current review focuses on prevention of accelerated aging and cognitive
      impairment through an unconventional approach of combining non-pharmacological
      (enriched environment) and pharmacological therapy, which reduces the factors
      responsible for accentuated aging and memory impairment in chronic epileptic
      condition.

PMID- 29471021
TI  - Does male preference play a role in maintaining female limited polymorphism in a
      Batesian mimetic butterfly?
AB  - Female-limited polymorphism occurs in multiple butterfly species with Batesian
      mimicry. While frequency-dependent selection is often argued as the driving force
      behind polymorphism in Batesian mimicry systems, male preference and alternative
      female mating strategies may also influence the maintenance of multiple female
      forms. Through a series of behavioural assays with the female-limited Batesian
      mimetic butterfly Papilio polytes, we show that males prefer stationary mimetic
      females over stationary non-mimetic females, but weigh female activity levels
      more heavily than female wing pattern when choosing between active mimetic and
      active non-mimetic females. Male preference for mimetic vs. non-mimetic females
      is independent of male genotype at the locus responsible for the female wing
      pattern, the autosomal gene doublesex. However male genotype does influence their
      response to active females. Male emphasis on female behaviour instead of
      appearance may reduce sexual selection pressures on female morphology, thereby
      facilitating frequency-dependent natural selection due to predation risk and
      toxic model abundance.

PMID- 29471023
TI  - Evidence of clinical response and stability of Ceftolozane/Tazobactam used to
      treat a carbapenem-resistant Pseudomonas Aeruginosa lung abscess on an outpatient
      antimicrobial program.

PMID- 29471024
TI  - In situ antimicrobial behavior of materials with copper-based additives in a
      hospital environment.
AB  - Copper and its alloys are effective antimicrobial surface materials in the
      laboratory and in clinical trials. Copper has been used in the healthcare setting
      to reduce environmental contamination, and thus prevent healthcare-associated
      infections, complementing traditional protocols. The addition of copper
      nanoparticles to polymer/plastic matrices can also produce antimicrobial
      materials, as confirmed under laboratory conditions. However, there is a lack of
      studies validating the antimicrobial effects of these nanocomposite materials in
      clinical trials. To satisfy this issue, plastic waiting room chairs with embedded
      metal copper nanoparticles, and metal hospital IV pools coated with an organic
      paint with nanostructured zeolite/copper particles were produced and tested in a
      hospital environment. These prototypes were sampled once weekly for 10 weeks and
      the viable microorganisms were analysed and compared with the copper-free
      materials. In the waiting rooms, chairs with copper reduced by around 73% the
      total viable microorganisms present, showing activity regardless of the
      microorganism tested. Although there were only low levels of microorganisms in
      the IV pools installed in operating rooms because of rigorous hygiene protocols,
      samples with copper presented lower total viable microorganisms than unfilled
      materials. Some results did not have statistical significance because of the low
      load of microorganisms; however, during at least three weeks the IV pools with
      copper had reduced levels of microorganisms by a statistically significant 50%.
      These findings show for the first time the feasibility of utilizing the
      antimicrobial property of copper by adding nanosized fillers to other materials
      in a hospital environment.

PMID- 29471025
TI  - Releasing iron from ferritin protein nanocage by reductive method: The role of
      electron transfer mediator.
AB  - BACKGROUND: Ferritin detoxifies excess of free Fe(II) and concentrates it in the
      form of ferrihydrite (Fe2O3.xH2O) mineral. When in need, ferritin iron is
      released for cellular metabolic activities. However, the low solubility of
      Fe(III) at neutral pH, its encapsulation by stable protein nanocage and presence
      of dissolved O2 limits in vitro ferritin iron release. METHODS: Physiological
      reducing agent, NADH (E1/2 = -330 mV) was inefficient in releasing the ferritin
      iron (E1/2 = +183 mV), when used alone. Thus, current work investigates the role
      of low concentration (5-50 MUM) of phenazine based electron transfer (ET)
      mediators such as FMN, PYO - a redox active virulence factor secreted by
      Pseudomonas aeruginosa and PMS towards iron mobilization from recombinant frog M
      ferritin. RESULTS: The presence of dissolved O2, resulting in initial lag phase
      and low iron release in FMN, had little impact in case of PMS and PYO, reflecting
      their better ET relay ability that facilitates iron mobilization. The molecular
      modeling as well as fluorescence studies provided further structural insight
      towards interaction of redox mediators on ferritin surface for electron relay.
      CONCLUSIONS: Reductive mobilization of iron from ferritin is dependent on the
      relative rate of NADH oxidation, dissolved O2 consumption and mineral core
      reduction, which in turn depends on E1/2 of these mediators and their interaction
      with ferritin. GENERAL SIGNIFICANCE: The current mechanism of in vitro iron
      mobilization from ferritin by using redox mediators involves different ET steps,
      which may help to understand the iron release pathway in vivo and to check
      microbial growth.

PMID- 29471026
TI  - Fungal extracellular vesicles: modulating host-pathogen interactions by both the
      fungus and the host.
AB  - The secretion of biomolecules by fungal cells occurs via the conventional export
      of signal peptide-coupled soluble molecules, but it also results from transport
      within extracellular vesicles (EV). During the last ten years since the
      description of this non-conventional secretion pathway, varied, interesting
      biological roles have been associated with EV release by fungi. The various
      organic molecules carried by these structures are involved in pathogenesis and
      immune evasion, and may be associated with cell-cell communication. In regards to
      host-pathogen interactions, EV roles are diverse and organism-specific, although
      some features seem to be conserved among the pathogenic fungal organisms studied
      to date. This review aims to highlight our current understanding of the
      biologically relevant findings regarding EV released by the pathogenic fungal
      organisms and describes our knowledge of the roles of EV in host-pathogen
      interactions.

PMID- 29471027
TI  - Cytotoxic homoisoflavonoids from the bulbs of Bellevalia flexuosa.
AB  - Four new homoisoflavonoids, 7-O-methyl-8-demethoxy-3'-hydroxy-3,9
      dihydropunctatin (4), 6-hydroxy-8-demethoxy-4'-O-methyl-3,9-dihydropunctatin (8),
      7,4'-O-dimethyl-8-demethoxy-3,3'-dihydroxy-3,9-dihydropunctatin (13), and 7-O
      methyl-3-hyroxy-3,9-dihydropunctatin (14) were identified from a chloroform
      extract of the bulbs of Bellevalia flexuosa, along with 13 known analogues. The
      structures were determined by analysis of HRMS and NMR data, while ECD
      spectroscopy enabled the assignment of the absolute configurations of the new
      compounds 4, 8, 13 and 16. The cytotoxic activities of the isolated compounds (1
      17) were evaluated using a panel of human cancer cell lines. Compounds 2 and 7
      were the most potent against the MDA-MB-435 (melanoma) cancer cell line with IC50
      values of 1.6 and 2.0 MUM, respectively, and were essentially equipotent against
      the OVCAR3 (ovarian) cancer cell line with IC50 values of 9.5 and 10.8 MUM,
      respectively. However, compound 7, with an IC50 value of 3.6 MUM, was the most
      potent against the MDA-MB-231 (breast) cancer cell line.

PMID- 29471028
TI  - The structural and functional brain networks that support human social networks.
AB  - Social skills rely on a specific set of cognitive processes, raising the
      possibility that individual differences in social networks are related to
      differences in specific brain structural and functional networks. Here, we tested
      this hypothesis with multimodality neuroimaging. With diffusion MRI (DMRI), we
      showed that differences in structural integrity of particular white matter (WM)
      tracts, including cingulum bundle, extreme capsule and arcuate fasciculus were
      associated with an individual's social network size (SNS). A voxel-based
      morphology analysis demonstrated correlations between gray matter (GM) volume and
      SNS in limbic and temporal lobe regions. These structural changes co-occured with
      functional network differences. As a function of SNS, dorsomedial and
      dorsolateral prefrontal cortex showed altered resting-state functional
      connectivity with the default mode network (DMN). Finally, we integrated these
      three complementary methods, interrogating the relationship between social GM
      clusters and specific WM and resting-state networks (RSNs). Probabilistic
      tractography seeded in these GM nodes utilized the SNS-related WM pathways.
      Further, the spatial and functional overlap between the social GM clusters and
      the DMN was significantly closer than other control RSNs. These integrative
      analyses provide convergent evidence of the role of specific circuits in SNS,
      likely supporting the adaptive behavior necessary for success in extensive social
      environments.

PMID- 29471029
TI  - The contribution of left heart disease in COPD patients with pulmonary
      hypertension.
AB  - BACKGROUND: Pulmonary hypertension (PH), regardless of its etiology, is
      associated with an impaired outcome in patients with chronic obstructive
      pulmonary disease (COPD). The aim of our study was to determine the incidence,
      cause, and effect of PH as detected by echocardiography in COPD patients.
      METHODS: Patients with confirmed COPD of any stage were evaluated by
      echocardiography for the likelihood of PH according to the proposed criteria.
      Patients with possible/likely to have PH underwent right heart catheterization,
      upon agreement, to confirm the presence, severity, and cause of PH. RESULTS: Of
      91 patients, 39 were in stable condition (group A) and 52 with COPD exacerbation
      (group B). Group B patients presented with PH and left ventricular diastolic
      dysfunction more often than group A patients. One of two fulfilled the criteria
      for possible/likely PH. The incidence of likely/possible PH was significantly
      higher in group B. Nineteen group B patients with likely/possible PH underwent
      RHC, and PH was confirmed in 15 cases and in 73.3% was associated with left heart
      disease. The presence of possible/likely PH was associated with a statistically
      significant increase in mortality compared to those with unlikely PH.
      CONCLUSIONS: The use of echocardiographic criteria for the presence of PH is
      adequate for the screening of COPD patients. Patients with acute exacerbation of
      COPD and possible/likely PH demonstrate worse mortality compared to patients
      unlikely to have PH.

PMID- 29471030
TI  - Neuroprotective effects of fecal microbiota transplantation on MPTP-induced
      Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-alpha
      signaling pathway.
AB  - Parkinson's disease (PD) patients display alterations in gut microbiota
      composition. However, mechanism between gut microbial dysbiosis and pathogenesis
      of PD remains unexplored, and no recognized therapies are available to halt or
      slow progression of PD. Here we identified that gut microbiota from PD mice
      induced motor impairment and striatal neurotransmitter decrease on normal mice.
      Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales
      decreased, while phylum Proteobacteria, order Turicibacterales and
      Enterobacteriales increased in fecal samples of PD mice, along with increased
      fecal short-chain fatty acids (SCFAs). Remarkably, fecal microbiota
      transplantation (FMT) reduced gut microbial dysbiosis, decreased fecal SCFAs,
      alleviated physical impairment, and increased striatal DA and 5-HT content of PD
      mice. Further, FMT reduced the activation of microglia and astrocytes in the
      substantia nigra, and reduced expression of TLR4/TNF-alpha signaling pathway
      components in gut and brain. Our study demonstrates that gut microbial dysbiosis
      is involved in PD pathogenesis, and FMT can protect PD mice by suppressing
      neuroinflammation and reducing TLR4/TNF-alpha signaling.

PMID- 29471031
TI  - Authors' response.

PMID- 29471032
TI  - Results of an asthma education program delivered via telemedicine in rural
      schools.
AB  - BACKGROUND: Asthma morbidity is high in low-income children living in rural US
      regions, yet few interventions have been designed to decrease the asthma burden
      in rural populations. OBJECTIVE: To examine the effect of a school-based asthma
      education program delivered by telemedicine in children living in an impoverished
      rural region. METHODS: We conducted a cluster randomized trial with rural
      children 7 to 14 years old by comparing a school-based telemedicine asthma
      education intervention with usual care. The intervention provided comprehensive
      asthma education by telemedicine to participants and provided evidence-based
      treatment recommendations to primary care providers. RESULTS: Of the 393 enrolled
      children, median age was 9.6 years, 81% were African American, and 47% lived in
      households with an annual income less than $14,999. At enrollment, 88% of
      children reported uncontrolled asthma symptoms. At the end of the intervention,
      there were no statistically significant differences in reported symptom-free days
      (primary outcome) for the intervention or usual-care group. Participants in the
      intervention group reported significantly higher use of peak flow meters to
      monitor asthma and reported taking their asthma medications as prescribed more
      frequently compared with the usual-care group. There were no changes in other
      outcome measures, including quality of life, self-efficacy, asthma knowledge, or
      lung function, between groups. CONCLUSION: Although there was some evidence of
      behavior change among intervention participants, these changes were inadequate to
      overcome the significant morbidity experienced by this highly symptomatic rural
      impoverished population. Future interventions should be designed with a
      multifaceted approach that considers caregiver engagement, distance barriers, and
      inadequate access to asthma providers in rural regions. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01167855.

PMID- 29471033
TI  - Inhibition of lymphocyte proliferation: An ability shared by murine mesenchymal
      stem cells, dermal fibroblasts and chondrocytes.
AB  - It has been demonstrated that mesenchymal stem cells (MSCs) have potent
      immunosuppressive capacities. But it is controversial whether differentiated
      mature stromal cells (SCs) share the immunosuppressive capacities. A previous
      study examined the ability of SCs from different human tissue sites to inhibit
      the proliferation of lymphocytes. The results are all positive but the mechanism
      isn't clear, and few mouse data have been published on this topic. Using an
      efficient mixed cell culture assay, our in vitro data show that the anti
      proliferative ability of murine MSCs on lymphocytes is shared by mature murine
      SCs, i.e. chondrocytes and fibroblasts. Though conflicting results have been
      published, our results suggest that nitric oxide and IFN-gamma are critical to
      the immunosuppressive effect. We also demonstrate that murine MSCs cultivated in
      chondrogenic differentiation medium still possess the anti-proliferative
      capacities on lymphocytes in vitro.

PMID- 29471035
TI  - How Safe Is the Safety Net? Comparison of Ivor-Lewis Esophagectomy at a Safety
      Net Hospital Using the NSQIP Database.
AB  - BACKGROUND: Recent data suggest that surgical outcomes at hospitals caring for
      low-income, vulnerable populations are suboptimal compared with outcomes from
      nonsafety-net hospitals. Therefore, the purpose of our study was to compare
      outcomes for patients who underwent an Ivor-Lewis esophagectomy at a safety-net
      hospital with the National Surgical Quality Improvement Program (NSQIP) database.
      STUDY DESIGN: We retrospectively reviewed the medical records of consecutive
      patients who underwent an Ivor-Lewis esophagectomy, between September 2013 and
      January 2017, at a single safety-net hospital. Patient characteristics and
      outcomes were compared with the 2013 to 2015 NSQIP database. Continuous variables
      were compared using Student's t-test, and categorical variables were analyzed
      using chi-square tests. Values of p < 0.05 were considered significant. RESULTS:
      We identified 78 patients from the safety-net hospital and 1,825 patients in the
      NSQIP database who underwent an Ivor-Lewis esophagectomy. Baseline
      characteristics were similar, except the safety-net hospital patients were more
      likely to have COPD (19.2% vs 8.1%; p = 0.001) and be current smokers (42.3% vs
      26.0%; p = 0.001); patients in the NSQIP group had a higher BMI (28 kg/m2 vs 26
      kg/m2; p = 0.001). There were no differences between groups for mortality,
      readmission, discharge destination, or mean operative time. Safety-net hospital
      patients had significantly fewer complications (16.7% vs 33.3%; p = 0.003), fewer
      reoperations (6.4% vs 14.5%; p = 0.046), and shorter hospital length of stay
      (10.3 vs 13.1 days; p = 0.001). CONCLUSIONS: Patients who underwent an Ivor-Lewis
      esophagectomy at a safety-net hospital had fewer complications and reoperations,
      and a shorter hospital length of stay compared with a national cohort. These
      findings illustrate the value of clinical pathways in optimizing the patient
      outcomes at safety-net hospitals and providing excellent care to their vulnerable
      patient population.

PMID- 29471036
TI  - eNOS S-nitrosylation mediated OxLDL-induced endothelial dysfunction via
      increasing the interaction of eNOS with beta-catenin.
AB  - Protein S-nitrosylation plays an important role in the progression of
      cardiovascular diseases. eNOS can be S-nitrosylated in endothelial cells, and
      this modification reversibly attenuates enzyme activity. Under physiological
      conditions, eNOS directly interacts with beta-catenin. However, whether and how
      eNOS S-nitrosylation regulates the beta-catenin signal pathway and participates
      in endothelial dysfunction remains unknown. Here, we show that OxLDL induces the
      S-nitrosylation of eNOS, which enhances the interaction between eNOS and beta
      catenin, transcriptional activity of beta-catenin, cell migration and adhesion
      molecule expression in endothelial cells. In addition, these effects are
      partially abolished after eNOS is mutated at Cys94 and Cys99, but not Cys441, in
      endothelial cells. Furthermore, OxLDL increases iNOS expression. The specific
      iNOS inhibitor 1400 W decreases eNOS S-nitrosylation and the association of eNOS
      and beta-catenin, thereby blocking the beta-catenin signal pathway to alleviate
      OxLDL-induced endothelial dysfunction. Taken together, OxLDL induces eNOS S
      nitrosylation at Cys94 and Cys99 via an iNOS-dependent manner, which may increase
      beta-catenin activation and trigger endothelial injury. This study describes a
      novel mechanism of endothelial dysfunction.

PMID- 29471034
TI  - The Microbiome and Hematopoietic Cell Transplantation: Past, Present, and Future.

PMID- 29471038
TI  - Co-delivery nanoparticle to overcome metastasis promoted by insufficient
      chemotherapy.
AB  - Heterogeneous distribution of drug inside tumor is ubiquitous, causing regional
      insufficient chemotherapy, which might be the hotbed for drug resistance, tumor
      cell repopulation and metastasis. Herein, we verify, for the first time, that
      heterogeneous drug distribution induced insufficient chemotherapy would
      accelerate the process of epithelial mesenchymal transition (EMT), consequently
      resulting in the promotion of tumor metastasis. To eliminate the insufficient
      chemotherapy promoted metastasis, we conceived a co-delivery strategy by
      hydroxyethyl starch-polylactide (HES-PLA) nanoparticle, in which DOX and TGF-beta
      receptor inhibitor, LY2157299 (LY), were administered together. In vitro and in
      vivo studies demonstrate that this co-delivery strategy can simultaneously
      suppress primary tumor and distant metastasis. Further study on
      immunofluorescence images of primary tumor verifies that low dose of DOX
      exasperates the EMT process, whereas the co-delivery nanoparticle can
      dramatically inhibit the progression of EMT. We reveal the impact of
      heterogeneous drug distribution on tumor metastasis and develop an effective co
      delivery strategy to suppress the metastasis, providing guidance for clinical
      cancer therapy.

PMID- 29471037
TI  - Butyrophilin3A proteins and Vgamma9Vdelta2 T cell activation.
AB  - Despite playing critical roles in the immune response and having significant
      potential in immunotherapy, gammadelta T cells have garnered little of the
      limelight. One major reason for this paradox is that their antigen recognition
      mechanisms are largely unknown, limiting our understanding of their biology and
      our potential to modulate their activity. One of the best-studied gammadelta
      subsets is the human Vgamma9Vdelta2T cell population, which predominates in
      peripheral blood and can combat both microbial infections and cancers. Although
      it has been known for decades that Vgamma9Vdelta2T cells respond to the presence
      of small pyrophosphate-based metabolites, collectively named phosphoantigens
      (pAgs), derived from microbial sources or malignant cells, the molecular basis
      for this response has been unclear. A major breakthrough in this area came with
      the identification of the Butyrophilin 3A (BTN3A) proteins, members of the
      Butyrophilin/Butyrophilin-like protein family, as mediators between pAgs and
      Vgamma9Vdelta2T cells. In this article, we review the most recent studies
      regarding pAg activation of human Vgamma9Vdelta2T cells, mainly focusing on the
      role of BTN3A as the pAg sensing molecule, as well as its potential impact on
      downstream events of the activation process.

PMID- 29471039
TI  - High-frequency, low-intensity ultrasound and microbubbles enhance nerve blockade.

PMID- 29471040
TI  - Biodistribution, activation, and retention of proinsulin-transferrin fusion
      protein in the liver: Mechanism of liver-targeting as an insulin prodrug.
AB  - A recombinant proinsulin-transferrin fusion protein (ProINS-Tf) has been
      previously reported to be a novel long-lasting INS analog, acting specifically on
      the inhibition of hepatic glucose output. In this study, we investigated the
      biodistribution, activation and tissue retention of ProINS-Tf to elucidate its
      liver targeted anti-diabetic mechanism. The biodistribution study revealed that
      ProINS-Tf exhibited liver specific accumulation after a single intravenous
      injection, whereas transferrin (Tf) or insulin (INS) showed relatively even
      distribution among different organs. The conversion of inactive ProINS-Tf into an
      active immune-reactive INS-Tf form (irINS-Tf) via a Tf receptor (TfR) mediated
      process only occurred in the liver, but not in other organs. In addition, ProINS
      Tf demonstrated a prolonged retention in the liver after an intravenous
      injection, suggesting the enhanced association of the bifunctional active form,
      irINS-Tf, within liver cells. Taken together, our results indicate that ProINS-Tf
      is a highly liver-targeted INS prodrug with a combination of 3 specific actions
      in liver cells: (1) TfR-mediated binding and uptake of the prodrug on the cell
      surface, (2) liver-specific, TfR-mediated conversion of the prodrug into its
      active form, and (3) the bifunctional binding of the active fusion protein to
      both Tf and INS receptors in the liver to achieve prolonged retention and thus
      enhanced anti-diabetic activities.

PMID- 29471041
TI  - Mechanically activated ion channels.
AB  - The ability of cells to sense and respond to their physical environment is
      fundamental to a broad spectrum of biological processes. Cells express an array
      of force sensors that can transduce mechanical inputs into biochemical signals,
      including the mechanically activated ion channels PIEZO1, PIEZO2 and TRPV4. The
      identification and characterisation of mechanically activated ion channels has
      proven challenging, as has identifying their mode of activation and regulation in
      vivo. However, the diverse channelopathies associated with the known channels
      highlights their physiological importance.

PMID- 29471042
TI  - Aspirin-induced attenuation of adipogenic differentiation of bone marrow
      mesenchymal stem cells is accompanied by the disturbed epigenetic modification.
AB  - Aspirin has positive effects on bone marrow mesenchymal stem cells (BMSCs)
      osteogenic differentiation. However, researchers did not give much thought to its
      effect on BMSCs adipogenic differentiation. Here, we analyzed the effect of
      aspirin on the BMSCs adipogenic differentiation. To detect whether the effect of
      aspirin on the adipogenic differentiation of BMSCs is associated with the
      disturbed epigenetic modification, the expression of histone deacetylases
      (HDACs), activity of HDACs and HAT, global histone H3 acetylation and H3k9
      acetylation alterations were investigated. Moreover, to further explore and
      understand the binding mode between aspirin and HDACs, an attempt was made to
      identify the interaction between aspirin and the HDACs with the aid of in silico
      docking study. The results showed that aspirin could induce inhibition of BMSCs
      adipogenesis. The level of HDAC activity, global histone H3 acetylation, and H3k9
      acetylation were all down regulated during adipogenic differentiation, and
      aspirin can reverse these decreases. Furthermore, the HDAC isoforms have
      different expression patterns in those progresses. The expression of HDAC9 was
      increased in a does-dependent manner when aspirin was introduced during BMSCs
      adipogenic differentiation. Docking study showed that high affinity of HDAC9 to
      aspirin was existed, suggesting that HDAC9 may has an important role in the
      process of aspirin-induced suppression of adipogenesis. Further studies are
      needed to define the intricate mechanisms of the HDAC isoforms, and all of these
      enable us to understand aspirin and its efficacy of inhibition of adipogenic
      differentiation and pave the way to aspirin clinical using for the tissue
      regenerating.

PMID- 29471043
TI  - Public Reporting of Congenital Heart Surgery Outcomes: Counting Numbers, Caring
      for Patients.
AB  - The purpose of public reporting is to provide transparency and accountability so
      that patients and their families can make informed choices. Our ability to assess
      and publicly report quality in congenital cardiac surgery is constrained by the
      available data and statistical techniques. Efforts should be directed toward
      collecting and evaluating information that provides a broad picture of what makes
      a high-quality program. For public reporting to succeed, the outcomes presented
      must be accessible, relevant, and understandable.

PMID- 29471044
TI  - Engineered protein degradation of farnesyl pyrophosphate synthase is an effective
      regulatory mechanism to increase monoterpene production in Saccharomyces
      cerevisiae.
AB  - Monoterpene production in Saccharomyces cerevisae requires the introduction of
      heterologous monoterpene synthases (MTSs). The endogenous farnesyl pyrosphosphate
      synthase (FPPS; Erg20p) competes with MTSs for the precursor geranyl
      pyrophosphate (GPP), which limits the production of monoterpenes. ERG20 is an
      essential gene that cannot be deleted and transcriptional down-regulation of
      ERG20 has failed to improve monoterpene production. Here, we investigated an N
      degron-dependent protein degradation strategy to down-regulate Erg20p activity.
      Degron tagging decreased GFP protein half-life drastically to 1 h (degron K3K15)
      or 15 min (degrons KN113 and KN119). Degron tagging of ERG20 was therefore paired
      with a sterol responsive promoter to ensure sufficient metabolic flux to
      essential downstream sterols despite the severe destabilisation effect of degron
      tagging. A dual monoterpene/sesquiterpene (linalool/nerolidol) synthase, AcNES1,
      was used as a reporter of intracellular GPP and FPP production. Transcription of
      the synthetic pathway was controlled by either constitutive or diauxie-inducible
      promoters. A combination of degron K3K15 and the ERG1 promoter increased linalool
      titre by 27-fold to 11 mg L-1 in the strain with constitutive promoter
      constructs, and by 17-fold to 18 mg L-1 in the strain with diauxie-inducible
      promoter constructs. The sesquiterpene nerolidol remained the major product in
      both strains. The same strategies were applied to construct a limonene-producing
      strain, which produced 76 mg L-1 in batch cultivation. The FPPS regulation method
      developed here successfully redirected metabolic flux toward monoterpene
      production. Examination of growth defects in various strains suggested that the
      intracellular FPP concentration had a significant effect on growth rate. Further
      strategies are required to balance intracellular production of FPP and GPP so as
      to maximise monoterpene production without impacting on cellular growth.

PMID- 29471045
TI  - PRDM14, a putative histone methyl-transferase, interacts with and decreases the
      stability and activity of the HOXA1 transcription factor.
AB  - Understanding how the activity of transcription factors like HOX proteins is
      regulated remains a widely open question. In a recent screen for proteins
      interacting with HOXA1, we identified a PRDM protein family member, PRDM14, which
      is known to be transiently co-expressed with HOXA1 in epiblast cells before their
      specification towards somatic versus germ cell fate. Here, we confirm PRDM14 is
      an interactor of HOXA1 and we identify the homeodomain of HOXA1 as well as the PR
      domain and Zinc fingers of PRDM14 to be required for the interaction. An 11-His
      repeat of HOXA1 previously highlighted to contribute to HOXA1-mediated protein
      protein interactions is also involved. At a functional level, we provide evidence
      that HOXA1 displays an unexpectedly long half-life and demonstrate that PRDM14
      can reduce the stability and affect the transcriptional activity of HOXA1.

PMID- 29471046
TI  - Congenital microcephaly: A diagnostic challenge during Zika epidemics.
AB  - The multiple, wide and diverse etiologies of congenital microcephaly are complex
      and multifactorial. Recent advances in genetic testing have improved
      understanding of novel genetic causes of congenital microcephaly. The recent Zika
      virus (ZIKV) epidemic in Latin America has highlighted the need for a better
      understanding of the underlying pathological mechanisms of microcephaly including
      both infectious and non-infectious causes. The diagnostic approach to
      microcephaly needs to include potential infectious and genetic etiologies, as
      well as environmental in-utero exposures such as alcohol, toxins, and
      medications. Emerging genetic alterations linked to microcephaly include abnormal
      mitotic microtubule spindle structure and abnormal function of centrosomes. We
      discuss the diagnostic challenge of congenital microcephaly in the context of
      understanding the links with ZIKV emergence as a new etiological factor involved
      in this birth defect.

PMID- 29471047
TI  - A urinary biosignature for mitochondrial myopathy, encephalopathy, lactic
      acidosis and stroke like episodes (MELAS).
AB  - We used a comprehensive metabolomics approach to study the altered urinary
      metabolome of two mitochondrial myopathy, encephalopathy lactic acidosis and
      stroke like episodes (MELAS) cohorts carrying the m.3243A>G mutation. The first
      cohort were used in an exploratory phase, identifying 36 metabolites that were
      significantly perturbed by the disease. During the second phase, the 36 selected
      metabolites were able to separate a validation cohort of MELAS patients
      completely from their respective control group, suggesting usefulness of these 36
      markers as a diagnostic set. Many of the 36 perturbed metabolites could be linked
      to an altered redox state, fatty acid catabolism and one-carbon metabolism.
      However, our evidence indicates that, of all the metabolic perturbations caused
      by MELAS, stalled fatty acid oxidation prevailed as being particularly disturbed.
      The strength of our study was the utilization of five different analytical
      platforms to generate the robust metabolomics data reported here. We show that
      urine may be a useful source for disease-specific metabolomics data, linking,
      amongst others, altered one-carbon metabolism to MELAS. The results reported here
      are important in our understanding of MELAS and might lead to better treatment
      options for the disease.

PMID- 29471048
TI  - New innovative method relating guided surgery to dental implant placement.
AB  - INTRODUCTION: Companies selling dental implant guided systems mostly offer
      similar surgical guides. The purpose of this paper is to present an innovative
      guided surgery system which originality lies in its guidance device, and to
      report the author's experience in using this system for dental implant surgery.
      TECHNICAL PROTOCOL: Two parallel tubes on either side of the drilling axis guide
      the successive drills and the implant placement. As a result of the lateral
      guidance, there is no friction of the drills on the surgical guide, which would
      damage it or contaminate the drilling hole with particles torn out from the
      guide. No radiological guide is needed during the radiographic examination stage.
      No successive diameter reduction tubes are requested. This guide can be used for
      all brands of implants. DISCUSSION: In our experience, 67 implants (31 titanium
      and 36 zircon implants) were placed in 35 patients with guided surgery system.
      Multiple clinical cases were treated with this system: 'one-stage' or a 'two
      stage' surgical protocol, with flap and flapless surgical techniques, and with
      delayed or immediate loading. Clinical cases treated revealed good implant
      placement with planning. The widely open design of this guide allows irrigation
      and practitioner's sight control under conditions comparable to those of
      operations performed without surgical guide. CONCLUSION: This dental implant
      guided system appears to be a significant advance in the field of implant
      surgical guides.

PMID- 29471049
TI  - Temporomandibular joint arthroplasty for osteoarthrosis: A series of 24 patients
      that received a uni- or bilateral inter-positional silicone sheet.
AB  - PURPOSE: To evaluate mid-term results from using a silicone sheet for inter
      positional arthroplasty in moderate or severe cases of osteoarthrosis of the
      temporo-mandibular joint (TMJ). To also determine any remaining indications from
      this method. PATIENTS AND METHODS: This retrospective study included patients
      that underwent surgery between 2008 and 2016. Pre- and post-operative mouth
      opening (MO), according to inter-incisal distance (mm) and pain score (PS: 0=no
      pain to 4=very severe pain) were recorded for 24 patients. Patients were divided
      according to thickness of the silicone sheet (group A: 1.0 mm, group B: 1.5 mm).
      RESULTS: The cohort included 22 females (92%). Mean age at surgery was 55 years+/
      13 (26-80). Mean length of follow-up was 26 months+/-24 (6-80). Mean improvement
      in MO was 8.2 mm (+33%) and of PS was 1.7 (-68%). MO was not improved for two
      patients and worsened for one. PS score improved for all patients. No statistical
      difference was found between groups A and B. There was also a tendency for
      degradation of outcomes over time. CONCLUSION: The poor reputation of prosthetic
      discoplasty was not as evident in our series, even though anatomical and
      functional status seemed to deteriorate over time. This is because total-joint
      prosthetic replacement is often proposed instead. However, for elderly or fragile
      patients that have severe pain, and regarding cost-benefit aspects, conventional
      arthroplasty can still be discussed, especially since French national health-care
      insurance does not yet support TMJ prosthetic replacement for osteoarthrosis.

PMID- 29471050
TI  - The protein-protein interactions between Amsacta moorei entomopoxvirus (AMEV)
      protein kinases (PKs) and all viral proteins.
AB  - Entomopoxviruses are an important group of viruses infecting only insects. They
      belong to Poxviridae which infect both invertebrates and vertebrates, including
      humans. Protein kinases are known to have roles at virus morphogenesis, host
      selectivity, the regulation of cell division and apoptosis in some vertebrate
      poxviruses. In this study, 2 protein kinases (PKs) (AMV153 and AMV197) of Amsacta
      moorei entomopoxvirus (AMEV) were investigated for the interactions among 230
      viral proteins using yeast two-hybrid system (Y2H). For this purpose, two protein
      kinases and 230 viral genes were cloned into the bait and prey vectors,
      respectively. Bait vectors were introduced into Saccharomyces cerevisiae AH109.
      Expression of the bait genes were confirmed by western blot analysis. Both yeast
      strains of bait were transformed individually with each prey clone and grown on a
      selective medium (minimal synthetic defined) to determine the protein-protein
      interactions between bait and prey proteins. Transformations identified totally
      16 interactions among AMEV protein kinases and all viral proteins of which 5
      belong to AMV153 and 11 belong to AMV197. One of the five interactions detected
      for AMV153 protein kinase is self-association. Its other four interactions are
      with two virus entry complex proteins (AMV035 and AMV083), a membrane protein
      (AMV165) and a subunit of RNA polymerase (AMV230). The other protein kinase,
      AMV197, interacted with two virus entry complex proteins (AMV035 and AMV083) as
      AMV153, a caspase-2 enzyme (AMV063), a Holliday junction resolvase (AMV162), a
      membrane protein (AMV165), a subunit of RNA polymerase (AMV230) and five other
      hypothetical proteins (AMV026, AMV040, AMV062, AMV069, AMV120) encoded by AMEV
      genome. Glutathione S-transferase (GST) pull-down assay was used to confirm all
      interactions described by Y2H analysis. In addition, the theoretical structures
      of the two of 16 interactions were interpreted by docking analysis. Consistent
      with Y2H and pull down assays, docking analysis also showed the interactions of
      AMV063 with AMV153 and AMV197. Detected interactions of the AMEV viral proteins
      with viral protein kinases could lead to the understanding of the regulation of
      the viral activities of interacted viral proteins.

PMID- 29471051
TI  - An analysis of two open reading frames (ORF3 and ORF4) of rat hepatitis E virus
      genome using its infectious cDNA clones with mutations in ORF3 or ORF4.
AB  - Rat hepatitis E virus (ratHEV) genome has four open reading frames (ORFs: ORF1,
      ORF2, ORF3 and ORF4). The functions of ORF3 and ORF4 are unknown. An infectious
      cDNA clone (pUC-ratELOMB-131L_wt, wt) and its derivatives including ORF3
      defective (DeltaORF3) and ORF4-defective (DeltaORF4) mutants, were constructed
      and their full-length RNA transcripts transfected into PLC/PRF/5 cells. DeltaORF3
      replicated as efficiently as wt in cells. However, <=1/1000 of the number of
      progenies were detectable in the culture supernatant of DeltaORF3-infected cells
      compared with wt-infected cells. ORF4 protein was not detectable in ratHEV
      infected cells or in the liver tissues of ratHEV-infected rats. No marked
      differences were noted between wt and DeltaORF4 regarding the viral replication
      and protein expression. ORF3 mutants with proline-to-leucine mutations at amino
      acids (aa) 93, 96 and/or 98 in ORF3 were constructed and transfected into
      PLC/PRF/5 cells. Wt and an ORF3 mutant with leucine at aa 98 (ORF3-L98)
      replicated efficiently (density 1.15-1.16 g/cm3), while ORF3-L93 + L96 exhibited
      a decreased viral release and banded at 1.26-1.27 g/cm3, similar to DeltaORF3. In
      conclusion, the ORF3 protein, especially its proline residues at aa 93 and 96, is
      essential for the release of membrane-associated ratHEV particles, and ORF4 is
      unnecessary for the replication of ratHEV.

PMID- 29471052
TI  - Revisiting rabies virus neutralizing antibodies through infecting BALB/c mice
      with live rabies virus.
AB  - This study investigates the production of rabies virus (RABV) neutralizing
      antibody after virus infection through a mouse model. The BALB/c mice from
      different age groups (three, five, seven week old) were intramuscularly
      inoculated with live rabies virus (TX coyote 323R). Without pre-exposure or post
      exposure prophylaxis (PEP), we found there is a decreased fatality with increased
      age of animals, the mortalities are 60%, 50%, and 30%, respectively.
      Interestingly, through assay of rapid fluorescent focus inhibition test (RFFIT),
      direct fluorescent antibody (DFA) and quantitative Polymerase Chain Reaction
      (qPCR), the results showed that all the animals that succumbed to rabies
      challenge, except one, developed circulating neutralizing antibodies, and all the
      healthy animals, except two, did not generate virus neutralizing antibodies
      (VNA). Our animal study suggests that the induction of VNA was an indicator of
      infection progression in the central nervous system (CNS) and speculate that RABV
      neutralizing antibodies did not cross the blood-brain barrier of the CNS for
      those diseased animals. We hypothesize that early release of viral antigens from
      damaged nerve tissue might potentially be a benefit for survivors, and we also
      discuss several other aspects of the interaction of RABV and its neutralizing
      antibodies.

PMID- 29471055
TI  - Brain insulin signalling, glucose metabolism and females' reproductive aging: A
      dangerous triad in Alzheimer's disease.
AB  - Alzheimer's disease (AD) constitutes a major socioeconomic challenge due to its
      disabling features and the rise in prevalence (especially among (peri)menopausal
      women and type 2 diabetes patients). The precise etiopathogenesis of AD remains
      poorly understood. Importantly, its neurodegenerative perspective has been
      challenged towards a more "systemic" view. Amyloid-beta (Abeta) and
      hyperphosphorylated Tau protein (P-Tau) (the main AD neuropathological features)
      affect and are affected by peripheral and brain insulin signalling dysfunction,
      leading to glucose dysmetabolism, synaptic loss and AD-related cognitive
      deficits. This may be anticipated and exacerbated by the progressive loss of
      estrogen (and interactions, e.g., with insulin) during females' aging, increasing
      their risk for AD, especially during menopause. Under this perspective, we aimed
      to discuss the recent findings (and controversies) behind the peripheral view of
      AD, and the role for insulin deficits and brain glucose dysmetabolism in such
      diseased brain. We also focused on the metabolic shift and the putative effects
      of gender (especially during midlife/perimenopause) herein. We finally discussed
      AD as the potential "type 3 diabetes", and the therapeutic potential of restoring
      brain insulin levels or glucose energy metabolism via administration of
      intranasal insulin and use of ketogenic diets. In sum, AD appears to lie on an
      intricate crosstalk between age-related metabolic, hormonal and specific genetic
      changes that challenge its traditional view. Hence, clarification of AD risk
      factors (besides aging and gender) and pathophysiological mechanisms will allow
      to establish accurate preventive strategies, biomarkers and more efficient drugs 
      all urgent medical needs in our increasingly aged societies. This article is
      part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for
      Neurodegenerative Disorders.'

PMID- 29471054
TI  - Developmental changes of GABA immunoreactivity in cortico-thalamic networks of an
      absence seizure model.
AB  - Absence seizures (ASs) are associated with abnormalities in gamma-aminobutyric
      acid (GABA) neurotransmission in the thalamus and the cortex. In the present
      study, we used light microscopy GABA immunocytochemistry to quantify the GABA
      immunoreactive (GABA-IR) neurons and neuropil in the thalamic ventral basal (VB)
      nucleus, the nucleus reticularis thalami (NRT), the dorsal lateral geniculate
      (dLGN), the primary motor cortex (M1) and perioral region of the somatosensory
      cortex (S1po) of genetic absence epilepsy rats from Strasbourg (GAERS). We used
      both the relative non-epileptic control (NEC) and normal Wistar rats as control
      strains, and investigated GABA immunostaining at postnatal day 15 (P15), P25, and
      P90. The main findings were i) an increase in GABA-IR neuropil in the VB at P25
      and P90 in GAERS but not in NEC and Wistar rats; ii) an increase in NRT GABA-IR
      neurons in GAERS and NEC, but not Wistar, rats at both P25 and P90; and iii) an
      increase in GABA-IR neuron density in S1po of GAERS at P25 and P90 and in Wistar
      at P90. These results indicate that the increased GABAergic innervation in the VB
      at P25 most likely contributes to the enhanced tonic inhibition observed in GAERS
      prior to AS onset, whereas the lack of any anatomo-morphological GABAergic
      differences in GAERS S1po suggests that functional more than structural
      abnormalities underlie the origin of cortical paroxysms in S1po of this AS model.
      This article is part of the "Special Issue Dedicated to Norman G. Bowery".

PMID- 29471056
TI  - Number of raised steps: A tool to assess brief and intense effort involving
      anaerobic metabolism.
AB  - BACKGROUND: Although the initial anaerobic component of exercise adaptation is
      unavoidable, no specific functional test is available for use in routine non
      sporting practice to evaluate it. OBJECTIVE: To assess the bioenergetic and
      biomechanical properties of the Short and Fast Step Test (SFST), which consists
      of walking up and down a step as many times as possible in 1minute and to analyse
      its ability to explore the initial anaerobic component of effort in comparison to
      a reference self-paced step test. METHODS: Overall, 31 healthy subjects (19
      women; mean [SD] age, 32.4 [10.2] years) completed a test-retest of a self-paced
      step test and the SFST, with pre- and post-test measurement of blood lactate
      concentration and continuous recording of VO2 and modelling of excess post
      exercise oxygen consumption (EPOC), near-infrared spectroscopy (NIRS) of the
      quadriceps and mechanical power (estimated by the number of steps climbed and 3-D
      motion analysis). RESULTS: Both step tests were well tolerated. The reliability
      of the bioenergetics parameters, number of raised steps, mechanical power and
      NIRS tissue saturation index was good. Indirect mechanical power (estimated from
      number of steps) was correlated with direct power (computed from the centre of
      mass). Lactate accumulation was significantly increased during exercise with only
      the SFST (mean [SD] increase, 3.86 [3.26]mmolL-1 from resting values, P<0.05).
      EPOC was higher with the SFST than the self-paced step test (P<0.05). Only the
      SFST showed significant correlations between number of steps climbed and EPOC
      (r=0.84; P<0.001) and decreased tissue saturation index (NIRS) and EPOC area (r=
      0.39; P<0.05). CONCLUSIONS: SFST is feasible, well tolerated, reliable and
      responsive to explore a brief exercise involving anaerobic metabolism at
      submaximal intensity. The number of steps taken in 1minute seems a suitable
      parameter for practical application.

PMID- 29471057
TI  - Pediatric brain tumors: Update of proteome-based studies.
AB  - Pediatric brain tumors (PBTs) are the most common solid malignancies in childhood
      and continue to pose a serious burden to modern societies. Existing treatments
      impose debilitating effects on the developing child, highlighting the need for
      molecularly targeted treatments with reduced toxicity, as well as the necessity
      of markers that reliably assess efficacy of, and tumor response to targeted
      therapies of PBTs. On this regard advances in technologies of protein
      identification and quantification, the large-scale, high-throughput investigation
      of the proteome, as well the newly-emerging field of "proteogenomics" aim to
      further our knowledge towards understanding the molecular pathophysiology of
      PBTs. This mini review article presents all updates on knowledge produced and
      published during the last years on PBT research derived from "omics"
      technologies, mainly involving protein research and proteomics.

PMID- 29471053
TI  - Morphological and functional evidence of increased excitatory signaling in the
      prelimbic cortex during ethanol withdrawal.
AB  - Excessive alcohol consumption in humans induces deficits in decision making and
      emotional processing, which indicates a dysfunction of the prefrontal cortex
      (PFC). The present study aimed to determine the impact of chronic intermittent
      ethanol (CIE) inhalation on mouse medial PFC pyramidal neurons. Data were
      collected 6-8 days into withdrawal from 7 weeks of CIE exposure, a time point
      when mice exhibit behavioral symptoms of withdrawal. We found that spine maturity
      in prelimbic (PL) layer 2/3 neurons was increased, while dendritic spines in PL
      layer 5 neurons or infralimbic (IL) neurons were not affected. Corroborating
      these morphological observations, CIE enhanced glutamatergic transmission in PL
      layer 2/3 pyramidal neurons, but not IL layer 2/3 neurons. Contrary to our
      predictions, these cellular alterations were associated with improved, rather
      than impaired, performance in reversal learning and strategy switching tasks in
      the Barnes maze at an earlier stage of chronic ethanol exposure (5-7 days
      withdrawal from 3 to 4 weeks of CIE), which could result from the anxiety-like
      behavior associated with ethanol withdrawal. Altogether, this study adds to a
      growing body of literature indicating that glutamatergic activity in the PFC is
      upregulated following chronic ethanol exposure, and identifies PL layer 2/3
      pyramidal neurons as a sensitive target of synaptic remodeling. It also indicates
      that the Barnes maze is not suitable to detect deficits in cognitive flexibility
      in CIE-withdrawn mice.

PMID- 29471058
TI  - iTRAQ-based quantitative proteomic analysis reveals pathways associated with re
      establishing desiccation tolerance in germinating seeds of Caragana korshinskii
      Kom.
AB  - : Mature seeds of Caragana korshinskii Kom. lose desiccation tolerance (DT)
      during germination. However, DT can be re-induced by polyethylene glycol (PEG) or
      abscisic acid (ABA), and this provides a novel system to analyse the mechanism of
      DT. Although the global gene expression during the re-establishment of DT treated
      by PEG or ABA has been characterized, the changes in protein species abundance
      are still unknown. Here, we used an iTRAQ-based quantitative proteomics approach
      to perform a comparative analysis of protein abundances in germinated seeds of
      PEG-treated, ABA-treated and untreated radicles in response to the re
      establishment of DT. A total of 3009 proteins were quantified; compared with the
      untreated samples, 274 and 261 differentially abundant protein species were found
      in PEG- and ABA-treated samples, respectively. The observed protein abundance
      patterns showed a clear overlap in seeds with ABA-and PEG-induced re
      establishment of DT. During the re-establishment of DT, the expression of auxin
      repressed protein and metallothionien-like protein was induced, and the content
      of proline increased significantly; however, proteins related to cell
      proliferation were found to be expressed at lower levels, and the glycolytic
      pathway was partially inhibited. These results provide promising insights into
      the molecular mechanisms underlying the re-establishment of DT in germinated
      seeds. BIOLOGICAL SIGNIFICANCE: The major challenge for seed storage is the
      complexity of the tolerance to desiccation. Re-establishment of desiccation
      tolerance (DT) in germinating seed as a model was used for DT researching.
      Although several researches have been focusing on the transcriptome of DT re
      establishment, little proteomic information remained to be available. In the
      present study, the iTRAQ-based quantitative proteomic analysis was employed to
      identify the differentially accumulated protein species from radicles of
      germinating C. korshinskii seedling after ABA-, PEG- treatment or not. The data
      obtained not only provides basic information about proteome, but also
      characterize the quantitative changes that occur in the abundance of proteins
      species during DT re-establishment. These results are helpful understanding the
      mechanism of DT re-establishment induced by PEG or ABA.

PMID- 29471059
TI  - Endogenous molecules released by haemocytes receiving Sargassum oligocystum
      extract lead to downstream activation and synergize innate immunity in white
      shrimp Litopenaeus vannamei.
AB  - White shrimp Litopenaeus vannamei haemocytes receiving immunostimulating
      Sargassum oligocystum extract (SE) caused necrosis in haemocyte cells, which
      released endogenous EM-SE molecules. This study examined the immune response of
      white shrimp L. vannamei receiving SE and EM-SE in vitro and in vivo. Shrimp
      haemocytes receiving SE exhibited degranulation, changes in cell size and cell
      viability, necrosis and a release of EM-SE. Shrimp haemocytes receiving SE, EM
      SE, and the SE + EM-SE mixture (SE + EM-SE) increased their phenoloxidase (PO)
      activity which was significantly higher in shrimp haemocytes receiving the SE +
      EM-SE mixture. Furthermore, shrimp haemocytes receiving EM-SE showed
      degranulation and changes in cell size and cell viability. Shrimp receiving SE,
      EM-SE, and SE + EM-SE all increased their immune parameters, phagocytic activity,
      clearance efficiency and resistance to Vibrio alginolyticus, being significantly
      higher in shrimp receiving SE + EM-SE. Meanwhile, the recombinant
      lipopolysaccharide- and beta-1,3-glucan binding protein of L. vannamei (rLvLGBP)
      was bound to SE, EM-SE, and SE + EM-SE. We conclude that in shrimp haemocytes
      receiving a non-self molecule, SE in dying cells released EM-SE which led to
      downstream activation and synergization of the immune response. This study
      demonstrated that the innate immunity of shrimp was elicited and enhanced by a
      mixture of endogenous molecules and exogenous substances (or immunostimulants).

PMID- 29471060
TI  - Identification of three class A scavenger receptors from rainbow trout
      (Oncorhynchus mykiss): SCARA3, SCARA4, and SCARA5.
AB  - Class A scavenger receptors (SR-As) are a family of five surface receptors whose
      functions in mammals are associated with innate immunity; however, their role in
      fish immunity requires further elucidation. The present study identifies,
      performs sequence analysis, and constitutive transcript expression analysis for
      three SR-A family members, SCARA3, SCARA4 and SCARA5, from rainbow trout. This
      work will provide a basis for future studies on SR-A function and their role in
      innate immunity in this economically important fish.

PMID- 29471061
TI  - Effects of dietary inulin and mannan oligosaccharide on immune related genes
      expression and disease resistance of Pacific white shrimp, Litopenaeus vannamei.
AB  - The effects of inulin and mannan oligosaccharide (MOS) at different doses (2.5, 4
      and 10 mg/g) in singular or combined diet on growth rate, immune related genes
      expression, and resistance to white spot syndrome virus (WSSV) and Vibrio
      alginolyticus in Pacific white shrimp (Litopenaeus vannamei) were investigated.
      At the end of 28-day singular feeding experiment, the highest values of specific
      growth rate (SGR) and the expression of toll-like receptor1, 2 and 3 (TLR1, 2,
      3), signal transducer and activator of transcription (STAT), crustin, anti
      lipopolysaccharide factor (ALF) as well as prophenoloxidase (proPO) were observed
      in shrimp individually fed with 5 mg/g dietary inulin or MOS, respectively.
      Compared with individual treatments, diet containing combined prebiotics (5 mg/g
      inulin and MOS) significantly improved the expression of TLRs, STAT, proPO,
      crustin and ALF in L. vannamei after four-week feeding. Additionally, Pacific
      white shrimp fed with combined dietary prebiotics showed significantly higher
      expression of immune related genes and lower cumulative mortality in WSSV and
      Vibrio alginolyticus challenges, compared to the singular feeding groups and
      control. These results in the present study demonstrated that the combined
      supplementation of inulin (5 mg/g) and MOS (5 mg/g) remarkably enhanced innate
      immune response and pathogen resistance of shrimp, and should be considered as a
      promising immunostimulatory additive for the culture of Pacific white shrimp.

PMID- 29471063
TI  - Intermolecular interactions determined by NOE build-up in macromolecules from
      hyperpolarized small molecules.
AB  - The nuclear Overhauser effect (NOE) is a primary means to characterize
      intermolecular interactions using modern NMR spectroscopy. Multiple experiments
      measured using different mixing time can be used for quantifying NOE buildup and
      measuring cross-relaxation rates. However, this approach using conventional multi
      dimensional NMR is time consuming. Hyperpolarization by dissolution dynamic
      nuclear polarization (D-DNP) can generate deviations from equilibrium spin
      polarization by orders of magnitude, thereby enhancing signals and allowing to
      characterize NOE build up in real-time. Since most small molecules can be
      hyperpolarized using D-DNP, this method is applicable to the study of
      intermolecular interactions between small molecules and macromolecules. This
      application is demonstrated using a model system for host-guest interactions
      including the third generation polyamidoamine dendrimer (G3 PAMAM) and the
      pharmaceutical phenylbutazone (PBZ). After mixing 1H hyperpolarized PBZ with
      PAMAM, the NOE build up is directly observed at different sites of the dendrimer
      in series of one-dimensional NMR spectra. Cross-relaxation rates specific to
      individual source and target spins are determined from the build up curves.
      Further, the polarization enhancement is shown to be sufficiently large to allow
      identification of cross-peaks not observed in a conventional 2D-NOESY spectrum.
      The improved signal-to-noise ratio provided by hyperpolarization allows for
      characterizing the intermolecular interaction in an almost instantaneous
      measurement, opening an application to macromolecular and biomacromolecular NMR.

PMID- 29471062
TI  - Constitutive stimulatory G protein activity in limb mesenchyme impairs bone
      growth.
AB  - GNAS mutations leading to constitutively active stimulatory G protein alpha
      subunit (Gsalpha) cause different tumors, fibrous dysplasia of bone, and McCune
      Albright syndrome, which are typically not associated with short stature.
      Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide
      receptor, which couples to multiple G proteins including Gsalpha, leads to short
      bones with delayed endochondral ossification. It has remained unknown whether
      constitutive Gsalpha activity also impairs bone growth. Here we generated mice
      expressing a constitutively active Gsalpha mutant (Gsalpha-R201H) conditionally
      upon Cre recombinase (cGsalphaR201H mice). Gsalpha-R201H was expressed in
      cultured bone marrow stromal cells from cGsalphaR201H mice upon adenoviral-Cre
      transduction. When crossed with mice in which Cre is expressed in a tamoxifen
      regulatable fashion (CAGGCre-ERTM), tamoxifen injection resulted in mosaic
      expression of the transgene in double mutant offspring. We then crossed the
      cGsalphaR201H mice with Prx1-Cre mice, in which Cre is expressed in early limb
      bud mesenchyme. The double mutant offspring displayed short limbs at birth, with
      narrow hypertrophic chondrocyte zones in growth plates and delayed formation of
      secondary ossification center. Consistent with enhanced Gsalpha signaling, bone
      marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA.
      Our findings indicate that constitutive Gsalpha activity during limb development
      disrupts endochondral ossification and bone growth. Given that Gsalpha
      haploinsufficiency also leads to short bones, as in patients with Albright's
      hereditary osteodystrophy, these results suggest that a tight control of Gsalpha
      activity is essential for normal growth plate physiology.

PMID- 29471064
TI  - TMS SMART - Scalp mapping of annoyance ratings and twitches caused by
      Transcranial Magnetic Stimulation.
AB  - BACKGROUND: The magnetic pulse generated during transcranial magnetic stimulation
      (TMS) also stimulates cutaneous nerves and muscle fibres, with the most commonly
      reported side effect being muscle twitches and sometimes painful sensations.
      These sensations affect behaviour during experimental tasks, presenting a
      potential confound for 'online' TMS studies. NEW METHOD: Our objective was to
      systematically map the degree of disturbance (ratings of annoyance, pain, and
      muscle twitches) caused by TMS at 43 locations across the scalp. Ten participants
      provided ratings whilst completing a choice reaction time task, and ten different
      participants provided ratings whilst completing a 'flanker' reaction time task.
      RESULTS: TMS over frontal and inferior regions resulted in the highest ratings of
      annoyance, pain, and muscle twitches caused by TMS. We predicted the difference
      in reaction times (RT) under TMS by scalp location and subjective ratings.
      Frontal and inferior scalp locations showed the greatest cost to RTs under TMS
      (i.e., slowing), with midline sites showing no or minimal slowing. Increases in
      subjective ratings of disturbance predicted longer RTs under TMS. Critically,
      ratings were a better predictor of the cost of TMS than scalp location or scalp
      to-cortex distance. The more difficult 'flanker' task showed a greater effect of
      subjective disturbance. COMPARISON WITH EXISTING METHODS: We provide the data as
      an online resource (www.tms-smart.info) so that researchers can select control
      sites that account for the level of general interference in task performance
      caused by online single-pulse TMS. CONCLUSIONS: The peripheral sensations and
      discomfort caused by TMS pulses significantly and systematically influence RTs
      during single-pulse, online TMS experiments.

PMID- 29471065
TI  - Clustering fMRI data with a robust unsupervised learning algorithm for
      neuroscience data mining.
AB  - BACKGROUND: Clustering approaches used in functional magnetic resonance imaging
      (fMRI) research use brain activity to divide the brain into various parcels with
      some degree of homogeneous characteristics, but choosing the appropriate
      clustering algorithms remains a problem. NEW METHOD: A novel application of the
      robust unsupervised learning approach is proposed in the current study. Robust
      growing neural gas (RGNG) algorithm was fed into fMRI data and compared with
      growing neural gas (GNG) algorithm, which has not been used for this purpose or
      any other medical application. Learning algorithms proposed in the current study
      are fed with real and free auditory fMRI datasets. RESULTS: The fMRI result
      obtained by running RGNG was within the expected outcome and is similar to those
      found with the hypothesis method in detecting active areas within the expected
      auditory cortices. COMPARISON WITH EXISTING METHOD(S): The fMRI application of
      the presented RGNG approach is clearly superior to other approaches in terms of
      its insensitivity to different initializations and the presence of outliers, as
      well as its ability to determine the actual number of clusters successfully, as
      indicated by its performance measured by minimum description length (MDL) and
      receiver operating characteristic (ROC) analysis. CONCLUSIONS: The RGNG can
      detect the active zones in the brain, analyze brain function, and determine the
      optimal number of underlying clusters in fMRI datasets. This algorithm can define
      the positions of the center of an output cluster corresponding to the minimal MDL
      value.

PMID- 29471066
TI  - A pharmacokinetic study on lapatinib in type 2 diabetic rats.
AB  - BACKGROUND: Diabetes mellitus (DM) is a complex metabolic disorder which affects
      the function of numerous tissues and alters the pharmacokinetic parameters of
      many drugs. As many oncological patients are diabetics, it is important to
      determine the influence of this chronic disease on the pharmacokinetics (PK) of
      anticancer drugs. Lapatinib is a tyrosine kinase inhibitor (TKI), approved for
      the treatment of human epidermal growth factor receptor 2 (HER2)-positive
      metastatic breast cancer. The aim of the study was to compare the PK of lapatinib
      in normal and type 2 diabetes mellitus (T2DM) model rats. Additionally, the
      effect of lapatinib on blood glucose concentrations was examined. METHODS: The PK
      of lapatinib was studied in healthy rats (n=6, the healthy group) and T2DM model
      rats (n=6, the diabetic group). The rats received lapatinib orally as a single
      dose of 50mg. Plasma concentrations of lapatinib were measured with high
      performance liquid chromatography method coupled with a tandem mass spectrometry.
      RESULTS: The plasma concentrations of lapatinib were increased in the T2DM model
      rats. There were statistically significant differences between the groups in Cmax
      (p=0.0104) and AUC0-t (p=0.0265). The reduction of glycaemia in the range of 1.2
      41.5% and in the range of 4.1-36.8% was observed in the diabetic and healthy
      animals, respectively. CONCLUSIONS: Higher concentrations of lapatinib in the
      diabetic rats may suggest the need for application of lower doses of this TKI in
      patients with DM.

PMID- 29471067
TI  - The smell of renal protection against chronic kidney disease: Hydrogen sulfide
      offers a potential stinky remedy.
AB  - Chronic kidney disease (CKD) is a common global health challenge characterized by
      irreversible pathological processes that reduce kidney function and culminates in
      development of end-stage renal disease. It is associated with increased morbidity
      and mortality in addition to increased caregiver burden and higher financial
      cost. A central player in CKD pathogenesis and progression is renal hypoxia.
      Renal hypoxia stimulates induction of oxidative and endoplasmic reticulum stress,
      inflammation and tubulointerstitial fibrosis, which in turn, promote cellular
      susceptibility and further aggravate hypoxia, thus forming a pathological vicious
      cycle in CKD progression. Although the importance of CKD is widely appreciated,
      including improvements in the quality of existing therapies such as dialysis and
      transplantation, new therapeutic options are limited, as there is still increased
      morbidity, mortality and poor quality of life among CKD patients. Growing
      evidence indicates that hydrogen sulfide (H2S), a small gaseous signaling
      molecule with an obnoxious smell, accumulates in the renal medulla under hypoxic
      conditions, and functions as an oxygen sensor that restores oxygen balance and
      increases medullary flow. Moreover, plasma H2S level has been recently reported
      to be markedly reduced in CKD patients and animal models. Also, H2S has been
      established to possess potent antioxidant, anti-inflammatory, and anti-fibrotic
      properties in several experimental models of kidney diseases, suggesting that its
      supplementation could protect against CKD and retard its progression. The purpose
      of this review is to discuss current clinical and experimental developments
      regarding CKD, its pathophysiology, and potential cellular and molecular
      mechanisms of protection by H2S in experimental models of CKD.

PMID- 29471068
TI  - Weight loss decreases self-reported appetite and alters food preferences in
      overweight and obese adults: Observational data from the DiOGenes study.
AB  - People with obesity often struggle to maintain their weight loss after a weight
      loss period. Furthermore, the effect of weight loss on appetite and food
      preferences remains unclear. Hence this study investigated the effect of weight
      loss on subjective appetite and food preferences in healthy, overweight and obese
      volunteers. A subgroup of adult participants (n = 123) from the Diet Obesity and
      Genes (DiOGenes) study (subgroup A) was recruited from across six European
      countries. Participants lost >=8% of initial body weight during an 8-week low
      calorie diet (LCD). Subjective appetite and food preferences were measured before
      and after the LCD, in response to a standardized meal test, using visual analogue
      rating scales (VAS) and the Leeds Food Choice Questionnaire (FCQ). After the LCD,
      participants reported increased fullness (p < 0.05), decreased desire to eat (p <
      0.05) and decreased prospective consumption (p < 0.05) after consuming the test
      meal. An interaction effect (visit x time) was found for hunger ratings (p <
      0.05). Area under the curve (AUC) for hunger, desire to eat and prospective
      consumption was decreased by 18.1%, 20.2% and 21.1% respectively whereas AUC for
      fullness increased by 13.9%. Preference for low-energy products measured by the
      Food Preference Checklist (FPC) decreased by 1.9% before the test meal and by
      13.5% after the test meal (p < 0.05). High-carbohydrate and high-fat preference
      decreased by 11.4% and 16.2% before the test meal and by 17.4% and 22.7% after
      the meal (p < 0.05). No other effects were observed. These results suggest that
      LCD induced weight loss decreases the appetite perceptions of overweight
      volunteers whilst decreasing their preference for high-fat-, high-carbohydrate-,
      and low-energy products.

PMID- 29471070
TI  - Are there different types of dieters? A review of personality and dietary
      restraint.
AB  - We review the research on the association between personality and dietary
      restraint as measured by commonly-used self-report assessment instruments
      (Restraint Scale, TFEQ, DEBQ, and EDE-Q). In order to expand our understanding of
      the potentially different types of dieters, we examine the different personality
      profiles that emerge from existing studies of restraint and personality,
      including associations between restraint and body dissatisfaction and body focus,
      self-esteem, neuroticism, sensation seeking, impulsivity, perfectionism and
      narcissism. This research provides some preliminary evidence that different
      measures of restraint are associated not only with different eating behaviours,
      but that they capture different personality profiles.

PMID- 29471069
TI  - What's technology cooking up? A systematic review of the use of technology in
      adolescent food literacy programs.
AB  - Over one-third of adolescents are overweight or obese. Food literacy (FL), the
      ability to plan and manage, select, prepare, and eat healthy foods, is a
      contemporary concept that provides a mechanism to understand the relationship
      between food-related knowledge and skills and dietary intake. Innovative
      interventions which focus on the core concepts of FL and include generationally
      appropriate technology have the potential to provide positive impact on the
      dietary habits of adolescents. This systematic review followed PRISMA guidelines
      and employed the Downs and Black criteria for rating studies. Titles and
      abstracts of 545 articles were collected and reviewed from 13 electronic
      databases. Studies were selected if they were peer-reviewed, included adolescents
      12-19 years-old, incorporated concepts related to FL, and employed technology as
      part of the intervention. Eight studies, six randomized controlled trials (RCT)
      and two interventions without controls were included. Seven of the interventions
      used Internet or web-based platforms to access program components and all RCTs
      incorporated game elements. Studies included between two and four constructs of
      FL. All reported positive changes in food intake with five reporting significant
      positive pre- and post-intervention changes. Few technology-driven FL-related
      studies exist within the literature. Although all studies reported improvements
      in dietary intake, due to variation in program design, delivery, and evaluation
      it is difficult to tease out the effect of the technology component. Continued
      research is needed to: 1) determine the degree to which FL should be included in
      interventions to effect a positive change on dietary intake; 2) develop
      adolescent-specific FL measures to more appropriately evaluate changes in
      knowledge, food-related skills, and dietary intake; and 3) design technology
      driven interventions so that technology components can be analyzed separately
      from other program elements.

PMID- 29471071
TI  - Intragastric preloads of l-tryptophan reduce ingestive behavior via oxytocinergic
      neural mechanisms in male mice.
AB  - Human and laboratory animal studies suggest that dietary supplementation of a
      free essential amino acid, l-tryptophan (TRP), reduces food intake. It is unclear
      whether an acute gastric preload of TRP decreases consumption and whether central
      mechanisms underlie TRP-driven hypophagia. We examined the effect of TRP
      administered via intragastric gavage on energy- and palatability-induced feeding
      in mice. We sought to identify central mechanisms through which TRP suppresses
      appetite. Effects of TRP on consumption of energy-dense and energy-dilute
      tastants were established in mice stimulated to eat by energy deprivation or
      palatability. A conditioned taste aversion (CTA) paradigm was used to assess
      whether hypophagia is unrelated to sickness. c-Fos immunohistochemistry was
      employed to detect TRP-induced activation of feeding-related brain sites and of
      oxytocin (OT) neurons, a crucial component of satiety circuits. Also, expression
      of OT mRNA was assessed with real-time PCR. The functional importance of OT in
      mediating TRP-driven hypophagia was substantiated by showing the ability of OT
      receptor blockade to abolish TRP-induced decrease in feeding. TRP reduced intake
      of energy-dense standard chow in deprived animals and energy-dense palatable chow
      in sated mice. Anorexigenic doses of TRP did not cause a CTA. TRP failed to
      affect intake of palatable yet calorie-dilute or noncaloric solutions (10%
      sucrose, 4.1% Intralipid or 0.1% saccharin) even for TRP doses that decreased
      water intake in thirsty mice. Fos analysis revealed that TRP increases activation
      of several key feeding-related brain areas, especially in the brain stem and
      hypothalamus. TRP activated hypothalamic OT neurons and increased OT mRNA levels,
      whereas pretreatment with an OT antagonist abolished TRP-driven hypophagia. We
      conclude that intragastric TRP decreases food and water intake, and TRP-induced
      hypophagia is partially mediated via central circuits that encompass OT.

PMID- 29471072
TI  - Neuroreflex control of cardiovascular function is impaired after acute poisoning
      with chlorpyrifos, an organophosphorus insecticide: Possible short and long term
      clinical implications.
AB  - Although it is well-established that severe poisoning by organophosphorus (OP)
      compounds strongly affects the cardiorespiratory system, the effects of sub
      lethal exposure to these compounds on the neural control of cardiovascular
      function are poorly explored. The aim of this study was to evaluate the effects
      of acute sub-lethal exposure to chlorpyrifos (CPF), a commonly used OP
      insecticide, on three basic reflex mechanisms involved in blood pressure
      regulation, the peripheral chemoreflex, the baroreflex and the Bezold-Jarisch
      reflex. Adult male Wistar rats were injected intraperitoneally with a single dose
      of CPF (30 mg/kg) or saline (0.9%). 24 h after injections, cardiovascular
      reflexes were tested in awake rats. Potassium cyanide (KCN) and phenylbiguanide
      (PBG) were injected intravenously to activate the chemoreflex and the Bezold
      Jarisch reflex, respectively. The baroreflex was activated by phenylephrine and
      sodium nitroprusside infusions. Blood samples were taken for measurements of
      butyrylcholinesterase (BChE) activity while acetylcholinesterase (AChE) activity
      was measured in brainstem samples. Animals treated with CPF presented signs of
      intoxication such as ataxia, tremor, lacrimation, salivation, tetany, urination
      and defecation. The hypertensive and the bradycardic responses of the chemoreflex
      as well as the hypotensive and bradycardic responses of the Bezold-Jarisch reflex
      were attenuated in CPF treated animals (P < 0.05). Concerning the baroreflex
      responses, CPF treatment reduced the bradycardia plateau, the range and the gain
      of the reflex (P < 0.05). Plasma BChE and brainstem AChE were both reduced
      significantly after CPF treatment (P < 0.05). Our results showed that acute sub
      lethal exposure to CPF impairs the cardiovascular responses of homeostatic and
      defensive cardiovascular reflexes. These effects are associated with a marked
      inhibition of plasma BChE and brainstem AChE.

PMID- 29471073
TI  - The impact of chemotherapeutic drugs on the CYP1A1-catalysed metabolism of the
      environmental carcinogen benzo[a]pyrene: Effects in human colorectal HCT116
      TP53(+/+), TP53(+/-) and TP53(-/-) cells.
AB  - Polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) can induce
      cytochrome P450 1A1 (CYP1A1) via a p53-dependent mechanism. The effect of
      different p53-activating chemotherapeutic drugs on CYP1A1 expression, and the
      resultant effect on BaP metabolism, was investigated in a panel of isogenic human
      colorectal HCT116 cells with differing TP53 status. Cells that were TP53(+/+),
      TP53(+/-) or TP53(-/-) were treated for up to 48 h with 60 MUM cisplatin, 50 MUM
      etoposide or 5 MUM ellipticine, each of which caused high p53 induction at
      moderate cytotoxicity (60-80% cell viability). We found that etoposide and
      ellipticine induced CYP1A1 in TP53(+/+) cells but not in TP53(-/-) cells,
      demonstrating that the mechanism of CYP1A1 induction is p53-dependent; cisplatin
      had no such effect. Co-incubation experiments with the drugs and 2.5 MUM BaP
      showed that: (i) etoposide increased CYP1A1 expression in TP53(+/+) cells, and to
      a lesser extent in TP53(-/-) cells, compared to cells treated with BaP alone;
      (ii) ellipticine decreased CYP1A1 expression in TP53(+/+) cells in BaP co
      incubations; and (iii) cisplatin did not affect BaP-mediated CYP1A1 expression.
      Further, whereas cisplatin and etoposide had virtually no influence on CYP1A1
      catalysed BaP metabolism, ellipticine treatment strongly inhibited BaP
      bioactivation. Our results indicate that the underlying mechanisms whereby
      etoposide and ellipticine regulate CYP1A1 expression must be different and may
      not be linked to p53 activation alone. These results could be relevant for
      smokers, who are exposed to increased levels of BaP, when prescribing
      chemotherapeutic drugs. Beside gene-environment interactions, more considerations
      should be given to potential drug-environment interactions during chemotherapy.

PMID- 29471074
TI  - Do humans still forage in an obesogenic environment? Mechanisms and implications
      for weight maintenance.
AB  - Many people struggle to control their food intake and bodyweight. This is often
      interpreted as evidence that humans are generally predisposed to consume food
      when it is available, because adiposity offered insurance against the threat of
      starvation in our ancestral environment. In this paper we suggest that modern
      humans have actually inherited a far broader range of foraging skills that
      continue to influence our dietary behaviour. To evaluate this idea, we identify
      three challenges that would need to be addressed to achieve efficient foraging;
      (1) monitoring the 'procurement cost' of foods, (2) determining the energy
      content of foods, and (3) proactively adapting to perceived food insecurity. In
      each case, we review evidence drawn from controlled and observational studies of
      contemporary humans and conclude that psychological mechanisms that address these
      challenges are conserved. For contemporary humans who live in fast-paced
      obesogenic environments, this foraging 'toolkit' no longer serves the same
      function to which it was adapted, and in many cases, this leads to an increase in
      food intake. Understanding these forms of 'evolutionary mismatch' is important
      because it can provide a stronger theoretical basis for informed dietary
      interventions that leverage fundamental foraging goals rather than work against
      them.

PMID- 29471075
TI  - Interspecific variation in avian thermoregulatory patterns and heat dissipation
      behaviours in a subtropical desert.
AB  - Deserts are physiologically challenging environments for birds, with scarce,
      unpredictable water resources combined with air temperatures (Tair) regularly
      exceeding avian body temperature (Tb). For arid-zone birds, mismatches between
      water supply and demand are a constant threat, yet interspecific variation in
      trade-offs between hyperthermia avoidance and dehydration avoidance remain poorly
      understood, particularly for free-ranging individuals. We examined behavioural
      and physiological responses to high Tair in nine species representing three
      orders that vary substantially in their heat dissipation thresholds, specifically
      pant50, the Tair at which panting behaviour is present in 50% of observations.
      Birds housed during mid-summer in large free-flight aviaries in the Kalahari
      Desert each received a surgically-implanted Tb logger, and we quantified shade
      seeking, activity and panting behaviours to examine relationships between species
      specific pant50 and Tb regulation. Overall, species setpoint Tb values were
      higher (range: 41.4 +/- 0.5  degrees C to 43.1 +/- 0.4  degrees C) than expected
      with maximum Tb values of 43.4-45.5  degrees C. Interspecific variation in Tb
      patterns at high Tair was substantial, with Tb increasing with Tair in most
      species, whereas in others no pattern or a negative relationship between Tb and
      Tair was evident. Most species avoided prolonged hyperthermia, with reductions in
      activity and increased shade-seeking evidently adequate to manage heat load
      without resorting to hyperthermia in in several of our study species. Access to
      drinking water and food resources in captivity may have affected Tb patterns. Our
      data reveal that thermoregulation varies substantially among species, and suggest
      that free-ranging birds in hot, arid environments may maintain higher Tb than
      currently thought.

PMID- 29471076
TI  - Daily pattern of energy distribution and weight loss.
AB  - Timing of energy intake, a temporal dietary pattern, may enhance health. Eating a
      greater amount of energy earlier and a smaller amount of energy later in the day,
      a behavioral circadian rhythm, may assist with chronoenhancement.
      Chronoenhancement seeks to enhance entrainment (synchronization) of biological
      and behavioral circadian rhythms. In humans, research reports that eating a
      greater amount of energy early and a smaller amount of energy later in the day
      increases dietary induced thermogenesis, improves cardiometabolic outcomes, and
      enhances weight loss. However, little human research has examined if this eating
      pattern enhances regularity of biological circadian rhythm. In a randomized
      controlled 8-week pilot study, the influence of energy distribution timing on
      weight loss and regularity of sleep onset and wake times (marker for biological
      circadian rhythm) was examined. Within an hypocaloric, three-meal prescription,
      participants (n = 8) were assigned to either: 1) Morning: 50%, 30%, and 20% of
      kcal at breakfast, lunch, and dinner, respectively; or 2) Evening: 20%, 30%, and
      50% of kcal at breakfast, lunch, and dinner, respectively. Percent weight loss
      and regularity of sleep onset and wake times were significantly (p < 0.05)
      greater for Morning than Evening. To enhance understanding of the influence of
      energy distribution timing on health, longer studies conducted in free-living
      participants, with dietary intake assessed using time-stamped methods, that
      include measures of the circadian timing system are needed. This small review is
      based upon a symposium presentation at the Society of the Study of Ingestive
      Behavior in 2017.

PMID- 29471077
TI  - Fabrication of antibody-loaded microgels using microfluidics and thiol-ene
      photoclick chemistry.
AB  - Reducing burst effects, providing controlled release, and safeguarding biologics
      against degradation are a few of several highly attractive applications for
      microgels in the field of controlled release. However, the incorporation of
      proteins into microgels without impairing stability is highly challenging. In
      this proof of concept study, the combination of microfluidics and thiol-ene
      photoclick chemistry was evaluated for the fabrication of antibody-loaded
      microgels with narrow size distribution. Norbornene-modified eight-armed
      poly(ethylene glycol) with an average molecular mass of 10,000 Da, 20,000 Da, or
      40,000 Da were prepared as macromonomers for microgel formation. For
      functionalization, either hydrolytically cleavable ester or stable amide bonds
      were used. A microfluidic system was employed to generate precursor solution
      droplets containing macromonomers, the cross-linker dithiothreitol and the
      initiator Eosin-Y. Irradiation with visible light was used to trigger thiol-ene
      reactions which covalently cross-linked the droplets. For all bond-types,
      molecular masses, and concentrations gelation was very rapid (<20 s) and a
      plateau for the complex shear modulus was reached after only 5 min. The generated
      microgels had a rod-like shape and did not show considerable cellular toxicity.
      Stress conditions during the fabrication process were simulated and it could be
      shown that fabrication did not impair the activity of the model proteins lysozyme
      and bevacizumab. It was confirmed that the average hydrogel network mesh size was
      similar or smaller than the hydrodynamic diameter of bevacizumab which is a
      crucial factor for restricting diffusion and delaying release. Finally, microgels
      were loaded with bevacizumab and a sustained release over a period of 30 +/- 4
      and 47 +/- 7 days could be achieved in vitro.

PMID- 29471079
TI  - Exploring the utility of "next-generation" sequence data on inferring the
      phylogeny of the South American Valeriana (Valerianaceae).
AB  - This study aimed to investigate the phylogenetic utility of genotyping-by
      sequencing (GBS) data in the southern South American subclade of Valerianaceae
      (Dipsacales). The variety of forms that has arisen in this clade, presumably over
      the past 5-10 million years, has all the signatures of an adaptive and rapid
      radiation. While the phylogeny of Valerianaceae has received a great deal of
      attention in the last decade, species relationships have been hard to resolve
      using traditional phylogenetic markers. Here, we collected high-throughput
      genomic sequence data from reduced-representation libraries obtained through GBS
      protocols. Putative orthologs were identified using within- and among-sample
      clustering using the computer software pyRAD. We recovered over 3000 loci for 14
      species of southern South AmericanValeriana,with 140 loci present across all
      samples.We analyzed a set of phylogenetic trees generated from each locus using
      maximum likelihood methods, as well as multispecies coalescent (*BEAST) methods.
      For comparative purposes, we also used a supermatrix approach to infer the
      phylogeny for these taxa. Across different methods and data sets, we recovered
      consistent relationships for the southern South American valerians that we
      sampled with varying degrees of support.

PMID- 29471081
TI  - Schematic beliefs and problem solving performance predict depression in people
      experiencing persecutory delusions.
AB  - Depression occurring alongside psychosis is an important treatment target, both
      in its own right and as a potential maintenance factor for positive psychotic
      symptoms. The present paper reports a prospective longitudinal analysis of
      depression and its predictors over six months in a group of 60 participants
      experiencing persecutory delusions. We hypothesised that negative schematic
      beliefs about the self and problem solving difficulties would predict the
      persistence of depression over time. The results showed, as hypothesised, that
      more negative schematic beliefs about the self and poorer problem solving
      predicted higher depression scores six months later, beyond what could be
      predicted by baseline depression scores. These findings support a proposed role
      for schematic beliefs and problem solving difficulties in the perpetuation of
      depression occurring alongside psychosis, as has been substantiated for major
      depressive disorder. Interventionist research is warranted to confirm causal
      effects.

PMID- 29471080
TI  - Subjective age and risk of incident dementia: Evidence from the National Health
      and Aging Trends survey.
AB  - The present study examines the association between subjective age and risk of
      incident dementia in a large longitudinal sample of older adults. Participants
      were adults aged 65 years and older from the National Health and Aging Trends
      Study (NHATS). Subjective age, covariates, and cognitive status were assessed in
      2011 and cognitive status was again assessed in 2012, 2013, 2014 and 2015.
      Incident dementia was determined based on answers from self and proxy
      respondents. The analyses included 4262 participants without dementia at
      baseline. Adjusting for demographic factors and baseline cognition, an older
      subjective age was related to higher likelihood of incident dementia. This
      association was partly accounted by depressive symptoms. Beyond the effect of
      chronological age, feeling older is associated with the risk of incident
      dementia.

PMID- 29471078
TI  - Development of controlled drug delivery systems for bone fracture-targeted
      therapeutic delivery: A review.
AB  - Impaired fracture healing is a major clinical problem that can lead to patient
      disability, prolonged hospitalization, and significant financial burden. Although
      the majority of fractures heal using standard clinical practices, approximately
      10% suffer from delayed unions or non-unions. A wide range of factors contribute
      to the risk for nonunions including internal factors, such as patient age,
      gender, and comorbidities, and external factors, such as the location and extent
      of injury. Current clinical approaches to treat nonunions include bone grafts and
      low-intensity pulsed ultrasound (LIPUS), which realizes clinical success only to
      select patients due to limitations including donor morbidities (grafts) and
      necessity of fracture reduction (LIPUS), respectively. To date, therapeutic
      approaches for bone regeneration rely heavily on protein-based growth factors
      such as INFUSE, an FDA-approved scaffold for delivery of bone morphogenetic
      protein 2 (BMP-2). Small molecule modulators and RNAi therapeutics are under
      development to circumvent challenges associated with traditional growth factors.
      While preclinical studies has shown promise, drug delivery has become a major
      hurdle stalling clinical translation. Therefore, this review overviews current
      therapies employed to stimulate fracture healing pre-clinically and clinically,
      including a focus on drug delivery systems for growth factors, parathyroid
      hormone (PTH), small molecules, and RNAi therapeutics, as well as recent advances
      and future promise of fracture-targeted drug delivery.

PMID- 29471082
TI  - Anhedonic behavior and gamma-amino butyric acid during a sensitive period in
      female rats exposed to early adversity.
AB  - Early life adversity increases depressive behavior that emerges during
      adolescence. Sensitive periods have been associated with fewer GABAergic
      interneurons, especially parvalbumin (PV), brain derived growth factor, and its
      receptor, TrkB. Here, maternal separation (MS) and social isolation (ISO) were
      used to establish a sensitive period for anhedonic depression using the learned
      helplessness (LH) paradigm. Female Sprague-Dawley rat pups underwent MS for 4
      h/day or received typical care (CON) between postnatal days 2-20; for the ISO
      condition, separate cohorts were individually housed between days 20-40 or served
      as controls (CON2). Anhedonia was defined by dichotomizing subjects into two
      groups based on one standard deviation of the mean number of escapes for the CON
      group (<14). This approach categorized 22% of CON subjects and 44% of MS subjects
      as anhedonic (p < 0.05), similar to the prevalence in maltreated human
      populations. Only 12.5% of ISO rats met criterion versus 28.5% in CON2 rats.
      Levels of PV and TrkB were reduced in the amygdala and prelimbic prefrontal
      cortex (PFC) in MS rats with <14 escapes, but elevated in behaviorally resilient
      MS rats (>13 escapes). The number of escapes in MS subjects significantly
      correlated with PV and TrkB levels (PFC: r = 0.93 and 0.91 and amygdala: r = 0.63
      and 0.81, respectively; n = 9), but not in CON/ISO/CON2 subjects. Calretinin, but
      not calbindin, was elevated in the amygdala of MS subjects. These data suggest
      that low levels of PV and TrkB double the risk for anhedonia in females with an
      MS history compared to normal adolescent females.

PMID- 29471083
TI  - Imaging the penetration and distribution of zinc and zinc species after topical
      application of zinc pyrithione to human skin.
AB  - Zinc pyrithione is an active component incorporated in an extensive range of
      topically applied commercial products that are used worldwide. Despite its
      prevalence, no published study has investigated the penetration of zinc from the
      zinc pyrithione complex into human skin. Zinc is crucial for healthy skin
      function however an elevated concentration of labile zinc is toxic outside a
      narrow concentration range. Synchrotron X-ray fluorescence microscopy in
      conjunction with X-ray absorption near edge structure spectroscopy was used to
      map the deposition of zinc, quantitate the amount of zinc within the skin and to
      identify a change in the chemical form of zinc after application. This study has
      demonstrated a ~3.8 fold increase in zinc concentration within the viable
      epidermis (VE) after 24 h topical application of zinc pyrithione that increased
      significantly by ~250 fold after 48 h when compared to control skin. Confocal
      microscopy using a labile zinc specific dye, ZinPyr-1, showed that zinc
      pyrithione disrupted the skin cells zinc homeostasis and significantly increased
      the intracellular zinc concentration leading to cell toxicity. Overall, this
      study demonstrates that topical application of zinc pyrithione formulations leads
      to an increase in zinc penetration in human skin, consequently, raising concerns
      for potential localised toxicity to occur.

PMID- 29471084
TI  - Erratum to "Gene expression profiles modulated by the human carcinogen
      aristolochic acid I in human cancer cells and their dependence on TP53" [Toxicol.
      Appl. Pharmacol. 232(1) (2008) 86-98].

PMID- 29471085
TI  - Houttuynia cordata polysaccharides ameliorate pneumonia severity and intestinal
      injury in mice with influenza virus infection.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Hottuynia cordata is an important traditional
      Chinese medicine for the treatment of respiratory diseases including bacterial
      and viral infections. Polysaccharides isolated from Houttuynia cordata (HCP), as
      its main ingredients, have been demonstrated to ameliorate the LPS-induced acute
      lung injury in mice. The study aimed to determine the protective effects of HCP
      on multiple organ injury in influenza A virus (IAV) H1N1 infected mice and its
      primary mechanisms in anti-inflammation and immune regulation. MATERIALS AND
      METHODS: Mice were inoculated with IAV H1N1 and then treated with 20 or 40
      mg/kg/d of HCP for survival test and acute lung-gut injury test. RESULTS: The
      treatment with HCP resulted in an increase in the survival rate of H1N1 infected
      mice and the protection from lung and intestine injury, accompanied with the
      reduced virus replication. HCP markedly decreased the concentration of pulmonary
      proinflammatory cytokines/chemokines and the number of intestinal goblet cells,
      and strengthened the intestinal physical and immune barrier, according to the
      increase of sIgA and tight junction protein (ZO-1) in intestine. At the same
      time, the inhibition of inflammation in lung and gut was related to the
      suppressing of the expression of TLR4 and p-NFkappaB p65 in lung. CONCLUSIONS:
      These results indicated that HCP ameliorated lung and intestine injury induced by
      IAV attack. The mechanisms were associated with inhibition of inflammation,
      protection of intestinal barrier and regulation of mucosal immunity, which may be
      related to the regulation of gut-lung axis. As an alternative medicine, HCP may
      have clinical potential to treat IAV infection in human beings.

PMID- 29471086
TI  - Gastroprotective effect of ethanol extracts of cladodes and roots of Pilosocereus
      gounellei (A. Weber ex K. Schum.) Bly. Ex Rowl (Cactaceae) on experimental ulcer
      models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pilosocereus gounellei Cactaceae), popularly
      known as "xique xique", is a species native from Caatinga region of Northeast
      Brazil, which is used by traditional communities in folk medicine for a variety
      of health problems, especially inflammatory processes and gastritis. AIM OF THE
      STUDY: The present study investigates the possible gastric antiulceractivity of
      ethanol extracts obtained from the cladodes and roots of Pilosocereus gounellei
      (EECPG and EERPG, respectively) and mechanisms of action underlying this effect.
      MATERIALS AND METHODS: Mice were used for the evaluation of the acute toxicity,
      and mice and rats to study the gastroprotective activity. The gastroprotective
      action of EECPG and EERPG was analyzed in the absolute ethanol in mice, ischemia
      reperfusion and cold restraint stress in rats. In the investigation of the
      gastroprotective mechanisms of EECPG and EERPG, the participation of the NO and
      prostaglandins, the levels of the non-protein sulfhydril groups (NP-SH) and the
      catalase activity using the ethanol-induced gastric mucosa lesion model and the
      quantification of the gastric mucus and the antisecretory activity through
      pylorus ligature model in rats were analyzed. RESULTS: The animals did not
      present any signs of acute toxicity for the EECPG and EERPG, and it was not
      possible to calculate the DL50. EECPG and EERPG (200 and 400 mg/kg) exhibited a
      significant gastroprotective effect in absolute ethanol, ischemia-reperfusion
      induced and cold restraint stress gastric lesion models. Gastroprotection of
      EECPG and EERPG (200 mg/kg) was significantly decreased in pre-treated mice with
      L-NAME. Our studies revealed that EECPG and EERPG (200 mg/kg) prevented the
      decrease of the non-protein sulfhydril groups (NPSH) and increased the catalase
      levels in ethanol-treated animals. However, the gastric secretion parameters
      (volume, [H+], pH) did not show any alteration. CONCLUSIONS: Our results indicate
      that the ethanolic extract from the cladodes and roots of Pilosocereus gounellei
      exhibits a significant gastroprotection, because it inhibits the formation of
      gastric lesions using different models. The participation of the nitric oxide,
      prostaglandins, the non-protein sulfhydril groups (NP-SH), catalase seem to be
      involved in the gastroprotection activity of the EECPG and EERPG. Nevertheless,
      this activity does not seem to be related to antisecretory mechanisms.

PMID- 29471087
TI  - Decontamination of Hg(II) from aqueous solution using polyamine-co-thiourea
      inarched chitosan gel derivatives.
AB  - Ethylenediamine (EDA), triethylenetetramine (TETA) and tetraethylenepentamine
      (TEPA) had been successfully introduced into the structure of thiourea (TC)
      modified chitosan (CS) by using formaldehyde as linkage, respectively. The
      resulted materials, TC-CS, TC-EDA-CS, TC-TETA-CS, and TC-TEPA-CS were
      characterized and employed as adsorbents in batch experiment for the Hg(II)
      removal. We have found the modification enhanced the Hg(II) adsorption
      significantly in comparison with raw CS. Hg(II) adsorption amounts for all
      adsorbents increased gradually and reached maxima at pH>=4.0. The adsorption of
      Hg(II) achieved an equilibrium state within 12h with the process drove by the
      pseudo-second-order model. The ionic strength had no remarkable inhibition effect
      on Hg(II) adsorption. While the Hg(II) adsorption capacities of the adsorbents
      were strongly related with the modifier types and the length of the incorporating
      amino ligands. Langmuir model described Hg(II) adsorption well with the maximum
      adsorption capacities of prepared adsorbents in order of TC-EDA-CS (217.1mg/g)>TC
      CS (164.8mg/g)>TC-TETA-CS (149.7mg/g)>TC-TEPA-CS (140.6mg/g) at room temperature.
      The FT-IR and XPS investigations implied that Hg(II) ion adsorption mechanism was
      characterized by a complexation reaction process. Adsorbents could be readily
      regenerated and had great reusability potential in Hg(II) ions capture from
      aqueous solution.

PMID- 29471088
TI  - Characterization of highly branched dextran produced by Leuconostoc citreum B-2
      from pineapple fermented product.
AB  - A strain Leuconostoc citreum B-2 was isolated from homemade fermentation product
      of pineapple and its polysaccharide yield was 28.3g/L after cultivating the
      strain in Man-Rogosa-Sharpe (MRS) medium with 75g/L sucrose. The
      exopolysaccharide (EPS) was characterized by gas chromatography (GC), Fourier
      transform infrared (FT-IR) spectra, high-performance size-exclusion
      chromatography (HPSEC), nuclear magnetic resonance (NMR) spectroscopy and
      scanning electron microscope (SEM) analysis in present study. The monosaccharide
      composition of EPS was glucose and molecular weight was 3.77*106Da. FT-IR and NMR
      spectra revealed that the B-2 EPS was composed of 75% alpha-(1->6) linked d
      glucopyranose units existing in the main chain with 19% alpha-(1->3) branching
      and only a few alpha-(1->2) branching. The SEM of the dried EPS appeared
      irregular sheets with glittering surface and compact structure. Water solubility
      index and water holding capacity of B-2 EPS were 80% and 450%, respectively. All
      the mentioned characteristics suggested that the EPS has a potential application
      in the food, cosmetic and pharmaceuticals industry.

PMID- 29471089
TI  - Facile, green and scalable method to produce carrageenan-based hydrogel
      containing in situ synthesized AgNPs for application as wound dressing.
AB  - This manuscript was focused on introducing a facile, green and scalable method to
      produce kappa-carrageenan (kappaC) hydrogel membranes containing in situ
      synthesized silver nanoparticles (AgNPs). In a typical protocol, kappaC hydrogels
      were obtained by heating (sol phase), followed by cooling (gel phase) the
      polysaccharide solution, which enabled the simultaneous synthesis of AgNPs during
      the heating time. The as synthesized AgNPs were characterized
      spectrophotometrically, and by dynamic light scattering and transmission electron
      microscopy. The swelling properties at different pH and the antimicrobial
      activity of kappaC-AgNP hydrogel were investigated. AgNPs were mostly spherical
      in shape, crystalline in nature and measuring ca. 27nm in diameter. The in situ
      synthesis of AgNPs changed the swelling properties of kappaC hydrogel and also
      reduces its viscosity and gelling temperature. The AgNPs were continuously
      released from kappaC hydrogel for up to 48h in a concentration sufficient to
      prevent the bacterial growth as confirmed by antimicrobial tests. The simplicity
      involved in the AgNPs synthesis combined to the good spreadability of kappaC
      hydrogel makes this method suitable for scale-up to manufacturing quantities of
      wound dressing.

PMID- 29471090
TI  - Structure characterization of two functional polysaccharides from Polygonum
      multiflorum and its immunomodulatory.
AB  - Two purified polysaccharides named WPMP-1 and WPMP-2 were obtained from Polygonum
      multiflorum with an average molecular weight of 2.04kDa and 92.13kDa,
      respectively. Structural characterization revealed that WPMP-1was supposed to be
      a glucan composed of 1,4-linked alpha-d-Glcp, 1,4,6-linked alpha-d-Glcp, and
      terminal alpha-d-Glcp. WPMP-2 contained a complex branched structre formed by 1,2
      linked alpha-d-Rhap, 1,2,4-linked alpha-d-Rhap, 1,3,5-linked alpha-l-Ara, 1,5-
      linked alpha-l-Araf, terminal alpha-l-Araf, 1,4-linked beta-d-Galp, 1,4-linked
      alpha-d-GalpA, and 4-linked alpha-d-GalpA. In vitro, WPMPs were of activation
      effect on splenocyte and macrophages, and could also protect immunocyte against 5
      Fu induced immunosupression by restoring the proliferation rate, phagocytic index
      and cytokines secretion level. Moreover, the acid polysaccharide WPMP-2 exhibited
      better immunomodulatory activity than neutral polysaccharide WPMP-1, which
      indicated that the immunomodulatory activity of WPMPs were positively associated
      with higher content of uronic acid, percentage of rhamnose, arabinose and
      galactose, and branching degree. These findings could promote the polysaccharides
      from Polygonum multiflorum to be attractive functional food supplement and
      immunomodulatory adjuvant.

PMID- 29471091
TI  - Study of telomerase reverse transcriptase and uterine-ovarian-specific genes
      expression in the endometrial tissue of ovariectomized female Sprague-Dawley
      rats.
AB  - BACKGROUND: An in vivo study was carried out to study of telomerase reverse
      transcriptase and Uterine-Ovarian-specific genes expression in the endometrial
      tissue of ovariectomized female Sprague-Dawley rats. MATERIAL AND METHODS: Twenty
      four female Sprague-Dawley rats divided into 4 groups of six rats. The first and
      second groups were ovariectomized and given tamoxifen and tamoxifen-loaded SLN
      respectively for six days continuously. Group 3 served as the untreated
      ovariectomized control group and group 4 was made up of untreated normal healthy
      rats. At the end of the study, the rats were sacrificed and study of the genes
      expression and serum zinc and copper were carried out. RESULTS: The results
      showed that the expression of TERT in the group treated with tamoxifen, and
      tamoxifen-loaded solid lipid nanoparticles, significantly decreased (p<0.001)
      compared with ovariectomized control group. The results also revealed that the
      treatment with tamoxifen-loaded solid lipid nanoparticles increased expression of
      UO-44 gene compared to ovariectomized control group, while there was no
      difference between tamoxifen treated and control group. CONCLUSIONS:
      Encapsulation of tamoxifen in solid lipid nanoparticles increased its targeting
      efficiency and improved the impact of the drug on the serum levels of some trace
      elements.

PMID- 29471092
TI  - Purification and functional characterization of recombinant balsamin, a ribosome
      inactivating protein from Momordica balsamina.
AB  - Balsamin, a type I ribosome-inactivating protein (RIP), has been shown to inhibit
      HIV-1 replication at the translation step. Our recent studies have shown that
      balsamin also possess anti-tumor, antibacterial and DNase-like activity, however,
      the amount of natural balsamin in Momordica balsamina seeds is limited and
      preclinical studies require large quantities of pure, bioactive balsamin.
      Therefore, in this study, we cloned the balsamin gene, expressed it in E.coli
      BL21 (DE3) strain and purified it by nickel affinity chromatography. Functional
      analysis indicated that balsamin exhibits both RNA N-glycosidase activity,
      releasing the Endo-fragment from rabbit reticulocyte rRNA, and DNase-like
      activity, converting the supercoiled form of a plasmid into the linear form in a
      concentration-dependent manner. Analysis of secondary structure revealed that
      recombinant balsamin mainly consisted of alpha-helical and random coiled with
      minimal turns and beta-sheets. Recombinant balsamin was found to be stable in the
      temperature range of 20-60  degrees C and pH range of 6-9. Antimicrobial assays
      showed that the minimum inhibitory concentrations of recombinant balsamin for
      various pathogens ranged between 1.56 and 12.5 MUg/ml. Heterologous expression
      and purification of balsamin carries great importance as it provides an
      alternative approach for large-scale preparation of biologically active
      recombinant balsamin, which is difficult from its natural source.

PMID- 29471093
TI  - Chemical cross-linked polyvinyl alcohol/cellulose nanocrystal composite films
      with high structural stability by spraying Fenton reagent as initiator.
AB  - Cross-linked polyvinyl alcohol (PVA) composite films with high structural
      stability were prepared by free radical copolymerization between cellulose
      nanocrystal (CNC) and maleic anhydride (MAH) modified PVA through spraying Fenton
      free radical as initiator. The influence of chemical cross-linked and physical
      network structure on mechanical, thermal and water absorption properties of the
      composite films were investigated. Compared to PVA and PVA/CNC composite film,
      significant improvements in the mechanical, thermal and water uptake properties
      of the cross-linked composite film were found. The tensile strength of the cross
      linked composite film was enhanced from 23.1MPa (neat PVA film) and 32.6MPa
      (PVA/CNC-10%) to 42.5MPa, and the maximum thermal degradation temperature was
      increased from 266.8 degrees C and 281.2 degrees C to 366.7 degrees C (cross
      linked composite film). Besides, the water absorption was reduced from 385.9% and
      220.6% to 175.7% for cross-linked composite film. It indicates that compared with
      physical network structure in PVA/CNC composite film, the multiple cross-linked
      networks showed excellent thermal stability, resistance of water swelling and
      structural stability at the same CNC loading level. Thus, the PVA/CNC composite
      film with the multiple cross-linked network shows greater property
      reinforcements.

PMID- 29471094
TI  - Electrospinning of food-grade nanofibres from whey protein.
AB  - In this study, electrospinning has been employed to produce micro to nano scale
      fibres of whey protein in order to investigate their potential for use in the
      food industry. Initially, spinning of pure whey protein proved challenging; so in
      order to facilitate the spinning of freshly prepared aqueous solutions, small
      amounts of polyethylene oxide (as low as 1% w/w in solution) were incorporated in
      the spinning solutions. The electrospun composite polyethylene-oxide/whey fibres
      exhibited diameters in the region of 100 to 400 nm, showing the potential to
      build fibre bundles from this size up. Time-dependent examinations of pure whey
      protein aqueous solutions were conducted using rheometery and small angle neutron
      scattering techniques, with the results showing a substantial change in the
      solution properties with time and stirring; and allowing the production of
      fibres, albeit with large diameters, without the need for an additive. The
      spinability is related to the potential of the whey protein composites to form
      aggregate structures, either through hydration and interaction with neighbouring
      proteins, or through interaction with the polyethylene oxide.

PMID- 29471095
TI  - Proteomic of goat milk whey and its bacteriostatic and antitumour potential.
AB  - Goat whey is normally discarded in the milk processing industry. However, several
      studies have addressed its biological properties and possible use in human or
      animal diet. The present study aimed to analysis the protein profile of goat whey
      to evaluate its possible oxidant, antioxidant, antibacterial, antitumour, and
      cytotoxic activities in vitro against human erythrocytes. Goat whey was skimmed,
      and crude protein extract (CPE) was obtained. Next, protein fractions (F) were
      obtained using ammonium sulphate precipitation method. The proteins were
      characterized by SDS-PAGE, two-dimensional electrophoresis and soluble protein
      measurements. No significant differences were observed in protein profile of CPE,
      F 30-60% and F 60-90%. The highest protein content was found in F 60-90%
      (0.41mgP/mL). All samples, except F 0-30% showed bacteriostatic activity against
      different bacterial strains. Only CPE at a concentration of 1000MUg/mL was
      haemolytic against human erythrocytes. Oxidant activity against erythrocytes was
      not observed. Antioxidant activity was observed only for CPE. Cytotoxicity
      against C6 rat glioma cell line that was performed with CPE revealed tumour cell
      death>70% at concentrations of 0.05 and 0.1MUg/mL. These results demonstrate at
      first time that CPE may be used as an antioxidant, bacteriostatic and cytotoxic
      compound against tumour cells.

PMID- 29471096
TI  - Ionically crosslinked magnetic chitosan/kappa-carrageenan bioadsorbents for
      removal of anionic eriochrome black-T.
AB  - Magnetic bioadsorbents based on chitosan with different molecular weights were
      prepared. To stabilize under acidic condition the synthesized magnetic chitosan
      was crosslinked with kappa-carrageenan. The characterization of magnetic
      bioadsorbents revealed that the size of magnetic nanoparticles is affected by the
      chitosan molecular weight. Magnetic nanoparticles with larger sizes were obtained
      with the high molecular weight of chitosan. The removal of eriochrome black-T
      (EBT) by the magnetic bioadsorbents was investigated. The equilibrium adsorption
      isotherm data of EBT on bioadsorbents were found to be well explained through
      Langmuir isotherm model, from which the maximum adsorption capacities were found
      to be 280, 235, and 199mg/g for bioadsorbents prepared with low, medium, and high
      molecular weights of chitosan, respectively. A remarkable reduction in adsorption
      capacities of bioadsorbents was observed as the pH of dye solution was increased.
      The reduction in the dye adsorption under basic media suggested using a mild
      condition (pH=9) to recycle and reuse the bioadsorbents. Cyclic experiments
      indicated that current bioadsorbents can be effectively reused to remove anionic
      EBT from aqueous solutions. The removal efficiencies remained >93% even after
      five adsorption-desorption cycles, which suggest the present bioadsorbents as a
      great candidate in the wastewater treatment.

PMID- 29471097
TI  - Purification of a fragment obtained by autolysis of a PIIIb-SVMP from Bothrops
      alternatus venom.

PMID- 29471098
TI  - The role of effective connectivity between the task-positive and task-negative
      network for evidence gathering [Evidence gathering and connectivity].
AB  - Reports linking a 'jumping-to-conclusions' bias to delusions have led to growing
      interest in the neurobiological correlates of probabilistic reasoning. Several
      brain areas have been implicated in probabilistic reasoning; however, findings
      are difficult to integrate into a coherent account. The present study aimed to
      provide additional evidence by investigating, for the first time, effective
      connectivity among brain areas involved in different stages of evidence
      gathering. We investigated evidence gathering in 25 healthy individuals using
      fMRI and a new paradigm (Box Task) designed such as to minimize the effects of
      cognitive effort and reward processing. Decisions to collect more evidence
      ('draws') were contrasted to decisions to reach a final choice ('conclusions')
      with respect to BOLD activity. Psychophysiological interaction analysis was used
      to investigate effective connectivity. Conclusion events were associated with
      extensive brain activations in widely distributed brain areas associated with the
      task-positive network. In contrast, draw events were characterized by higher
      activation in areas assumed to be part of the task-negative network. Effective
      connectivity between the two networks decreased during draws and increased during
      conclusion events. Our findings indicate that probabilistic reasoning may depend
      on the balance between the task-positive and task-negative network, and that
      shifts in connectivity between the two may be crucial for evidence gathering.
      Thus, abnormal connectivity between the two systems may significantly contribute
      to the jumping-to-conclusions bias.

PMID- 29471099
TI  - The dynamics of error processing in the human brain as reflected by high-gamma
      activity in noninvasive and intracranial EEG.
AB  - Error detection in motor behavior is a fundamental cognitive function heavily
      relying on local cortical information processing. Neural activity in the high
      gamma frequency band (HGB) closely reflects such local cortical processing, but
      little is known about its role in error processing, particularly in the healthy
      human brain. Here we characterize the error-related response of the human brain
      based on data obtained with noninvasive EEG optimized for HGB mapping in 31
      healthy subjects (15 females, 16 males), and additional intracranial EEG data
      from 9 epilepsy patients (4 females, 5 males). Our findings reveal a multiscale
      picture of the global and local dynamics of error-related HGB activity in the
      human brain. On the global level as reflected in the noninvasive EEG, the error
      related response started with an early component dominated by anterior brain
      regions, followed by a shift to parietal regions, and a subsequent phase
      characterized by sustained parietal HGB activity. This phase lasted for more than
      1 s after the error onset. On the local level reflected in the intracranial EEG,
      a cascade of both transient and sustained error-related responses involved an
      even more extended network, spanning beyond frontal and parietal regions to the
      insula and the hippocampus. HGB mapping appeared especially well suited to
      investigate late, sustained components of the error response, possibly linked to
      downstream functional stages such as error-related learning and behavioral
      adaptation. Our findings establish the basic spatio-temporal properties of HGB
      activity as a neural correlate of error processing, complementing traditional
      error-related potential studies.

PMID- 29471101
TI  - On object selectivity and the anatomy of the human fusiform gyrus.
AB  - pFs is a functionally-defined region in the human brain that is involved in
      recognizing objects. A recent trend refers to pFs as the posterior fusiform
      sulcus, which is a neuroanatomical structure that does not exist. Here, we
      correct this mistake. To achieve this goal, we first recount the original
      definitions of pFs and then review the identification of sulci within and
      surrounding the fusiform gyrus (FG) including the mid-fusiform sulcus (MFS),
      which is a tertiary sulcus within the FG. We highlight that tertiary sulci, such
      as the MFS, are often absent from brain atlases, which complicates the accurate
      localization of functional regions, as well as the understanding of structural
      functional relationships in ventral temporal cortex (VTC). When considering the
      location of object-selective pFs from previously published data relative to the
      sulci surrounding the FG, as well as the MFS, we illustrate that (1) pFs spans
      several macroanatomical structures, which is consistent with the original
      definitions of pFs (Grill-Spector et al., 1999, 2000), and (2) the topological
      relationship between pFs and MFS has both stable and variable features. To
      prevent future confusion regarding the anatomical location of functional regions
      within VTC, as well as to complement tools that automatically identify sulci
      surrounding the FG, we provide a method to automatically identify the MFS in
      individual brains using FreeSurfer. Finally, we highlight the benefits of using
      cortical surface reconstructions in large datasets to identify and quantify
      tertiary sulci compared to classic dissection methods because the latter often
      fail to differentiate tertiary sulci from shallow surface indentations produced
      by veins and arteries. Altogether, we propose that the inclusion of definitions
      and labels for tertiary sulci in neuroanatomical atlases and neuroimaging
      software packages will enhance understanding of functional-structural
      relationships throughout the human brain.

PMID- 29471100
TI  - Dynamic fMRI networks predict success in a behavioral weight loss program among
      older adults.
AB  - More than one-third of adults in the United States are obese, with a higher
      prevalence among older adults. Obesity among older adults is a major cause of
      physical dysfunction, hypertension, diabetes, and coronary heart diseases. Many
      people who engage in lifestyle weight loss interventions fail to reach targeted
      goals for weight loss, and most will regain what was lost within 1-2 years
      following cessation of treatment. This variability in treatment efficacy suggests
      that there are important phenotypes predictive of success with intentional weight
      loss that could lead to tailored treatment regimen, an idea that is consistent
      with the concept of precision-based medicine. Although the identification of
      biochemical and metabolic phenotypes are one potential direction of research,
      neurobiological measures may prove useful as substantial behavioral change is
      necessary to achieve success in a lifestyle intervention. In the present study,
      we use dynamic brain networks from functional magnetic resonance imaging (fMRI)
      data to prospectively identify individuals most likely to succeed in a behavioral
      weight loss intervention. Brain imaging was performed in overweight or obese
      older adults (age: 65-79 years) who participated in an 18-month lifestyle weight
      loss intervention. Machine learning and functional brain networks were combined
      to produce multivariate prediction models. The prediction accuracy exceeded 95%,
      suggesting that there exists a consistent pattern of connectivity which correctly
      predicts success with weight loss at the individual level. Connectivity patterns
      that contributed to the prediction consisted of complex multivariate network
      components that substantially overlapped with known brain networks that are
      associated with behavior emergence, self-regulation, body awareness, and the
      sensory features of food. Future work on independent datasets and diverse
      populations is needed to corroborate our findings. Additionally, we believe that
      efforts can begin to examine whether these models have clinical utility in
      tailoring treatment.

PMID- 29471102
TI  - High fructose diet-induced metabolic syndrome: Pathophysiological mechanism and
      treatment by traditional Chinese medicine.
AB  - Fructose is a natural monosaccharide broadly used in modern society. Over the
      past few decades, epidemiological studies have demonstrated that high fructose
      intake is an etiological factor of metabolic syndrome (MetS). This review
      highlights research advances on fructose-induced MetS, especially the underlying
      pathophysiological mechanism as well as pharmacotherapy by traditional Chinese
      medicine (TCM), using the PubMed, Web of science, China National Knowledge
      Infrastructure, China Science and Technology Journal and Wanfang Data. This
      review focuses on de novo lipogenesis (DNL) and uric acid (UA) production, two
      unique features of fructolysis different from glucose glycolysis. High level of
      DNL and UA production can result in insulin resistance, the key pathological
      event in developing MetS, mostly through oxidative stress and inflammation. Some
      other pathologies like the disturbance in brain and gut microbiota in the
      development of fructose-induced MetS in the past years, are also discussed. In
      management of MetS, TCM is an excellent representative in alternative and
      complementary medicine with a complete theory system and substantial herbal
      remedies. TCMs against MetS or MetS components, including Chinese patent
      medicines, TCM compound formulas, single TCM herbs and active compounds of TCM
      herbs, are reviewed on their effects and molecular mechanisms. TCMs with
      hypouricemic activity, which specially target fructose-induced MetS, are
      highlighted. And new technologies and strategies (such as high-throughput assay
      and systems biology) in this field are further discussed. In summary, fructose
      induced MetS is a multifactorial disorder with the underlying complex mechanisms.
      Current clinical and pre-clinical evidence supports the potential of TCMs in
      management of MetS. Additionally, TCMs may show some advantages against complex
      MetS as their holistic feature through multiple target actions. However, further
      work is needed to confirm the effectivity and safety of TCMs by high-standard
      clinical trials, clarify the molecular mechanisms, and develop new anti-MetS
      drugs by development and application of optimized and feasible strategies and
      methods.

PMID- 29471103
TI  - Embelin and its derivatives unravel the signaling, proinflammatory and
      antiatherogenic properties of GPR84 receptor.
AB  - GPR84 is an orphan G-protein coupled receptor, expressed on monocytes,
      macrophages and neutrophils and is significantly upregulated by inflammatory
      stimuli. The physiological role of GPR84 remains largely unknown. Medium chain
      fatty acids (MCFA) activate the receptor and have been proposed to be its
      endogenous ligands, although the high concentrations of MCFAs required for
      receptor activation generally exceed normal physiological levels. We identified
      the natural product embelin as a highly potent and selective surrogate GPR84
      agonist (originally disclosed in patent application WO2007027661A2, 2007) and
      synthesized close structural analogs with widely varying receptor activities.
      These tools were used to perform a comprehensive study of GPR84 signaling and
      function in recombinant cells and in primary human macrophages and neutrophils.
      Activation of recombinant GPR84 by embelin in HEK293 cells results in Gi/o as
      well as G12/13-Rho signaling. In human macrophages, GPR84 initiates PTX sensitive
      Erk1/2 and Akt phosphorylation, PI-3 kinase activation, calcium flux, and release
      of prostaglandin E2. In addition, GPR84 signaling in macrophages elicits Gi
      Gbetagamma-mediated augmentation of intracellular cAMP, rather than the decrease
      expected from Gialpha engagement. GPR84 activation drives human neutrophil
      chemotaxis and primes them for amplification of oxidative burst induced by FMLP
      and C5A. Loss of GPR84 is associated with attenuated LPS-induced release of
      proinflammatory mediators IL-6, KC-GROalpha, VEGF, MIP-2 and NGAL from peritoneal
      exudates. While initiating numerous proinflammatory activities in macrophages and
      neutrophils, GPR84 also possesses GPR109A-like antiatherosclerotic properties in
      macrophages. Macrophage receptor activation leads to upregulation of cholesterol
      transporters ABCA1 and ABCG1 and stimulates reverse cholesterol transport. These
      data suggest that GPR84 may be a target of therapeutic value and that distinct
      modes of receptor modulation (inhibition vs. stimulation) may be required for
      inflammatory and atherosclerotic indications.

PMID- 29471104
TI  - Cellular senescence as a therapeutic target to improve renal transplantation
      outcome.
AB  - Kidney transplants from aged donors are more vulnerable to ischemic injury,
      suffer more from delayed graft function and have a lower graft survival compared
      to kidneys from younger donors. On a cellular level, aging results in an increase
      in cells that are in a permanent cell cycle arrest, termed senescence, which
      secrete a range of pro-inflammatory cytokines and growth factors. Consequently,
      these senescent cells negatively influence the local milieu by causing
      inflammaging, and by reducing the regenerative capacity of the kidney. Moreover,
      the oxidative damage that is inflicted by ischemia-reperfusion injury during
      transplantation can induce senescence and accelerate aging. In this review, we
      describe recent developments in the understanding of the biology of aging that
      have led to the development of a new class of therapeutic agents aimed at
      eliminating senescent cells. These compounds have already shown to be able to
      restore tissue homeostasis in old mice, improve kidney function and general
      health- and lifespan. Use of these anti-senescence compounds holds great promise
      to improve the quality of marginal donor kidneys as well as to remove senescent
      cells induced by ischemia-reperfusion injury. Altogether, senescent cell removal
      may increase the donor pool, relieving the growing organ shortage and improve
      long-term transplantation outcome.

PMID- 29471105
TI  - Icariin doped bioactive glasses seeded with rat adipose-derived stem cells to
      promote bone repair via enhanced osteogenic and angiogenic activities.
AB  - AIMS: Cell communication between mesenchymal stem cells and blood vessel cells
      are crucial for bone repair. We have previously shown that the phyto-molecule
      icariin significantly promoted osteogenic differentiation of rat adipose-derived
      stem cells (ASCs). In the present study, we aimed to investigate the relationship
      between icariin induced osteogenic differentiation of ASCs and angiogenesis of
      rat endothelial progenitor cells (EPCs). Besides, we used icariin doped 45S5
      Bioglass seeded with ASCs to promote bone healing in rat calvarial bone defect
      models. MAIN METHODS: The conditioned medium from undifferentiated ASCs (ASCs-CM)
      and icariin induced ASCs (Icariin-ASCs-CM) was obtained and the vascular
      endothelial growth factor (VEGF) protein secretion level was measured. The
      angiogenic capacity and molecular mechanism of ASC-CM and Icariin-ASCs-CM on rat
      EPCs was analyzed. Rat calvarial bone defect models were established and treated
      with scaffolds implantation. Micro-CT imaging, histological and
      immunohistological staining were performed on the isolated specimens at 12 weeks
      post-surgery. KEY FINDINGS: VEGF protein expression was significantly increased
      after icariin treatment with the highest expression in the 10-7 M icariin group.
      Icariin-ASCs-CM obviously increased the angiogenesis of rat EPCs and this
      capacity was inhibited by a VEGF/VEGF receptor-specific binding inhibitor
      bevacizumab. Results of the in vivo investigations showed that all scaffolds
      promoted bone healing compared to the Control group. Icariin significantly
      improved the healing capacity of 45S5 Bioglass seeded with ASCs. SIGNIFICANCE:
      Implantation of Icariin/45S5 Bioglass seeded with rat ASCs could obviously
      promote both osteogenesis and angiogenesis and therefore represents an ideal
      candidate bone substitutes for bone repair and regeneration.

PMID- 29471106
TI  - Historical and contemporary features of infections due to Clostridium novyi.
AB  - Clostridium novyi is an anaerobic bacterium that resides in the soil in nature
      and that may cause severe clinical infections in humans. It is named after
      Frederick Novy, who incidentally discovered the anaerobic organism responsible
      for septicemia in rabbits. In this paper, we explore the circumstances
      surrounding the identification of the organism. In particular, we address who
      Novy was and what he was trying to do when he first described the organism in the
      1890s. We then address what is known about the biological features of the
      organism today, as well as the clinical syndromes that are now recognized to be
      associated with the microbe. Finally, we review efforts that have been made to
      use the organism for potential beneficial purposes for humans.

PMID- 29471107
TI  - PICK1 deficiency exacerbates sepsis-associated acute lung injury and impairs
      glutathione synthesis via reduction of xCT.
AB  - The role of oxidative stress has been well documented in the development of
      sepsis-induced acute lung injury (ALI). Protein interaction with C-kinase 1
      (PICK1) participates in oxidative stress-related neuronal diseases. However, its
      function in lung infections and inflammatory diseases is not known. We therefore
      sought to investigate whether PICK1 is involved in sepsis-induced ALI. Cecal
      ligation and puncture (CLP) was performed in anesthetized wild type (WT) and
      PICK1 knock out (KO, PICK1-/-) mice with C57BL/6 background. At the time of CLP,
      mice were given fluid resuscitation. Mouse lungs were harvested at 24 and 72 h
      for Western blot analysis, qRT-PCR, BALF analysis, Hematoxylin and Eosin
      staining, TUNEL staining, maleimide staining, flow cytometry analysis, GCL, GSH,
      GSSG and cysteine levels measurement. A marked elevation of PICK1 mRNA and
      protein level were demonstrated in lung tissue, which was accompanied by
      increased production of reactive oxygen species (ROS) and reactive nitrogen
      species (RNS) and consumption of glutathione (GSH). N-acetylcysteine (NAC),
      buthionine sulfoximine (BSO) and GSH-monoethyl ester (GSH-MEE) were injected into
      mice via caudal vein to regulate glutathione (GSH) level in lung. Alterations of
      lung GSH content induced PICK1 level change after CLP challenge. In PICK1-/-
      underwent with CLP, lung injury and survival were significantly aggravated
      compared with wild-type mice underwent with CLP. Concomitantly, CLP-induced lung
      cell apoptosis was exacerbated in PICK1-/- mice. The level of xCT, other than
      PKCalpha, in lung tissue was significantly lowered in PICK1-/- but not in wild
      type that underwent CLP surgery. Meanwhile, Nrf2 activation, which dominating xCT
      expression, was inhibited in PICK1-/- but not in wild type mice that underwent
      CLP surgery, as well. Moreover, higher level of PICK1 was detected in PBMCs of
      septic patients than healthy controls. Taken together, PICK1 plays a pivotal role
      in sepsis-induced ALI by regulating GSH synthesis via affecting the substrate
      specific subunit of lung cystine/glutamate transporter, xCT.

PMID- 29471108
TI  - Redox stress in Marfan syndrome: Dissecting the role of the NADPH oxidase NOX4 in
      aortic aneurysm.
AB  - Marfan syndrome (MFS) is characterized by the formation of ascending aortic
      aneurysms resulting from altered assembly of extracellular matrix fibrillin
      containing microfibrils and dysfunction of TGF-beta signaling. Here we identify
      the molecular targets of redox stress in aortic aneurysms from MFS patients, and
      investigate the role of NOX4, whose expression is strongly induced by TGF-beta,
      in aneurysm formation and progression in a murine model of MFS. Working models
      included aortae and cultured vascular smooth muscle cells (VSMC) from MFS
      patients, and a NOX4-deficient Marfan mouse model (Fbn1C1039G/+-Nox4-/-).
      Increased tyrosine nitration and reactive oxygen species levels were found in the
      tunica media of human aortic aneurysms and in cultured VSMC. Proteomic analysis
      identified nitrated and carbonylated proteins, which included smooth muscle alpha
      actin (alphaSMA) and annexin A2. NOX4 immunostaining increased in the tunica
      media of human Marfan aorta and was transcriptionally overexpressed in VSMC.
      Fbn1C1039G/+-Nox4-/- mice aortas showed a reduction of fragmented elastic fibers,
      which was accompanied by an amelioration in the Marfan-associated enlargement of
      the aortic root. Increase in the contractile phenotype marker calponin in the
      tunica media of MFS mice aortas was abrogated in Fbn1C1039G/+-Nox4-/- mice.
      Endothelial dysfunction evaluated by myography in the Marfan ascending aorta was
      prevented by the absence of Nox4 or catalase-induced H2O2 decomposition. We
      conclude that redox stress occurs in MFS, whose targets are actin-based
      cytoskeleton members and regulators of extracellular matrix homeostasis.
      Likewise, NOX4 have an impact in the progression of the aortic dilation in MFS
      and in the structural organization of the aortic tunica media, the VSMC
      phenotypic modulation, and endothelial function.

PMID- 29471109
TI  - Extensively drug-resistant Acinetobacter baumannii bacteraemia in a
      multidisciplinary intensive care unit during a 6-year period: Risk factors for
      fulminant sepsis.
AB  - OBJECTIVES: This study aimed to determine potential host-, pathogen-, infection-
      and treatment-related risk factors that might predict a fulminant fatal course of
      bacteraemia caused by extensively drug-resistant Acinetobacter baumannii (XDR
      Aba). METHODS: Eighty-seven patients with monomicrobial growth of XDR-Aba in
      blood cultures within a 6-year period (2011-2016) were studied. Patients were
      divided into three groups according to ICU outcome: Group A (n=40) consisted of
      patients who survived; Group B (n=10) included patients with fulminant sepsis who
      died early (<=48h); and Group C (n=37) included patients who died later (>48h)
      after the onset of bacteraemia. RESULTS: Regarding patient co-morbidities,
      patients who died from fulminant XDR-Aba bacteraemia had a significantly higher
      prevalence of chronic renal failure compared with patients who survived (40.0%
      vs. 7.5%; P=0.029). Patients with fulminant sepsis showed more severe organ
      dysfunction based on SOFA score compared with survivors (10.83+/-2.93 vs. 6.65+/
      3.6; P=0.013). The primary to secondary bacteraemia ratio and appropriate
      treatment were similar among the three outcome groups. Patients with fulminant
      bacteraemia displayed higher rates of colistin-, tigecycline- and pandrug
      resistant strains, although not statistically significant. CONCLUSIONS: Patients
      suffering from a fulminant course of XDR-Aba bacteraemia showed significantly
      higher rates of chronic renal failure and multiple organ dysfunction. Resistance
      patterns of XDR-Aba isolates and receipt of appropriate treatment did not affect
      outcomes. Further studies including larger samples of patients along with
      investigation of specific virulence determinants of individual Aba strains are
      needed.

PMID- 29471110
TI  - Antagonistic and synergistic interactions during the binding of binary mixtures
      of polycyclic aromatic hydrocarbons to the aryl hydrocarbon receptor.
AB  - In order to assess the potential of polycyclic aromatic hydrocarbons (PAHs) to
      interact with each other, benzo(a)pyrene (B(a)P) was incubated either alone or in
      combination with other isomeric 5-ring PAHs in precision-cut rat liver slices. At
      the end of the incubation, the slices were removed and the O-deethylation of
      ethoxyresorufin (EROD) was determined in microsomal preparations. The BP-mediated
      rise in EROD activity was suppressed in the presence of dibenzo(a,j)anthracene,
      dibenzo(a,c)anthracene and picene, whereas it was increased in the presence of
      pentacene. In the case of benzo(b)chrysene, benzo(c)chrysene and benzo(g)chrysene
      the effect was concentration-dependent with both antagonism and synergism being
      observed. The binding of B(a)P to the aryl hydrocarbon (Ah) receptor was
      similarly modulated by other PAHs. No correlation was evident between binding
      avidity of the PAH to the Ah receptor and either its potential for interaction or
      nature of interaction, e.g. synergism or antagonism. These interactions were also
      independent of the molecular shape (ring arrangement) of the 5-ring isomeric
      PAHs. Bearing in mind the role of the Ah receptor in chemical carcinogenesis, it
      may be concluded that interactions at the Ah receptor site may contribute to the
      well-established modulation of the carcinogenicity of one PAH in the presence of
      another.

PMID- 29471111
TI  - Mortality prediction in intensive care units (ICUs) using a deep rule-based fuzzy
      classifier.
AB  - Electronic health records (EHRs) contain critical information useful for clinical
      studies. Early assessment of patients' mortality in intensive care units is of
      great importance. In this paper, a Deep Rule-Based Fuzzy System (DRBFS) was
      proposed to develop an accurate in-hospital mortality prediction in the intensive
      care unit (ICU) patients employing a large number of input variables. Our main
      contribution is proposing a system, which is capable of dealing with big data
      with heterogeneous mixed categorical and numeric attributes. In DRBFS, the hidden
      layer in each unit is represented by interpretable fuzzy rules. Benefiting the
      strength of soft partitioning, a modified supervised fuzzy k-prototype clustering
      has been employed for fuzzy rule generation. According to the stacked approach,
      the same input space is kept in every base building unit of DRBFS. The training
      set in addition to random shifts, obtained from random projections of prediction
      results of the current base building unit is presented as the input of the next
      base building unit. A cohort of 10,972 adult admissions was selected from Medical
      Information Mart for Intensive Care (MIMIC-III) data set, where 9.31% of patients
      have died in the hospital. A heterogeneous feature set of first 48 h from ICU
      admissions, were extracted for in-hospital mortality rate. Required preprocessing
      and appropriate feature extraction were applied. To avoid biased assessments,
      performance indexes were calculated using holdout validation. We have evaluated
      our proposed method with several common classifiers including naive Bayes (NB),
      decision trees (DT), Gradient Boosting (GB), Deep Belief Networks (DBN) and D-TSK
      FC. The area under the receiver operating characteristics curve (AUROC) for NB,
      DT, GB, DBN, D-TSK-FC and our proposed method were 73.51%, 61.81%, 72.98%,
      70.07%, 66.74% and 73.90% respectively. Our results have demonstrated that DRBFS
      outperforms various methods, while maintaining interpretable rule bases. Besides,
      benefiting from specific clustering methods, DRBFS can be well scaled up for
      large heterogeneous data sets.

PMID- 29471112
TI  - Evaluation of Two Commercial Real-Time PCR Kits for Aspergillus DNA Detection in
      Bronchoalveolar Lavage Fluid in Patients with Invasive Pulmonary Aspergillosis.
AB  - Invasive pulmonary aspergillosis (IPA) is a common complication of
      immunosuppression. Rapid diagnosis using molecular techniques is essential to
      improve patient survival. PCR techniques are promising in enhancing Aspergillus
      detection in blood and respiratory samples. We evaluate for the first time the
      performances of two commercial real-time PCR kits, the A. fumigatus Bio-Evolution
      and the MycoGENIE A. fumigatus for the detection of A. fumigatus DNA in
      bronchoalveolar lavage (BAL) from patients with and without IPA. Seventy-three
      BAL samples were included. Thirty-one of them corresponded to patients with
      probable IPA, 11 to patients with possible IPA, and 31 to patients without
      aspergillosis, according to the 2008 European Organization for Research and
      Treatment of Cancer/Mycoses Study Group criteria. In the probable IPA group, A.
      fumigatus Bio-Evolution and the MycoGENIE A. fumigatus real-time PCR kits showed
      a specificity of 100% and a sensitivity of 81% and 71%, respectively. The A.
      fumigatus Bio-Evolution detected Aspergillus DNA in the 14 BAL samples with a
      positive Aspergillus culture result, whereas the MycoGENIE A. fumigatus PCR
      result was positive only for 12. In the possible IPA group, there were no
      positive real-time PCR or positive Aspergillus culture results. For the patients
      without aspergillosis, no positive result was observed for real-time PCR kit,
      despite the presence of various other non-Aspergillus pathogens in this group.
      Our study demonstrates an excellent specificity and a good sensitivity of A.
      fumigatus DNA detection in BAL samples with both kits.

PMID- 29471113
TI  - Validation of a Customized Bioinformatics Pipeline for a Clinical Next-Generation
      Sequencing Test Targeting Solid Tumor-Associated Variants.
AB  - Bioinformatic analysis is an integral and critical part of clinical next
      generation sequencing. It is especially challenging for some pipelines to
      consistently identify insertions and deletions. We present the validation of an
      open source tumor amplicon pipeline (OTA-pipeline) for clinical next-generation
      sequencing targeting solid tumor-associated variants. Raw data generated from 557
      TruSight Tumor 26 samples and in silico data were analyzed by the OTA-pipeline
      and legacy pipeline and compared. Discrepant results were confirmed by orthogonal
      methods. The OTA-pipeline reported 22 variants that were not detected by the
      previously validated pipeline, including seven synonymous or intronic single
      nucleotide variants, five single-nucleotide variants at frequency <5%, one
      insertion, and nine deletions. Variant allele frequencies reported by the two
      pipelines were highly concordant, although a few significant discrepancies were
      present. Analysis of in silico FASTQ files demonstrated a higher sensitivity of
      detecting complex insertions and deletions with the OTA-pipeline. The higher
      sensitivity came at a cost, because false-positive calls were increased in
      difficult-to-sequence regions. However, these calls were all flagged by our
      strand bias filter, distinguishing them from true variants. Our validation
      process provides a model for laboratories that want to establish an in-house
      bioinformatics pipeline for clinical next-generation sequencing.

PMID- 29471114
TI  - Reference Size Matching, Whole-Genome Amplification, and Fluorescent Labeling as
      a Method for Chromosomal Microarray Analysis of Clinically Actionable Copy Number
      Alterations in Formalin-Fixed, Paraffin-Embedded Tumor Tissue.
AB  - Cancer genome copy number alterations (CNAs) assist clinicians in selecting
      targeted therapeutics. Solid tumor CNAs are most commonly evaluated in formalin
      fixed, paraffin-embedded (FFPE) tissue by fluorescence in situ hybridization.
      Although fluorescence in situ hybridization is a sensitive and specific assay for
      interrogating preselected genomic regions, it provides no information about
      coexisting clinically significant copy number changes. Chromosomal microarray
      analysis is an alternative DNA-based method for interrogating genome-wide CNAs in
      solid tumors. However, DNA extracted from FFPE tumor tissue produces an
      essential, yet problematic, sample type. The College of American
      Pathologists/American Society of Clinical Oncology guidelines for optimal tumor
      tissue handling, published in 2007 for breast cancer and in 2016 for
      gastroesophageal adenocarcinomas, are lacking for other solid tumors. Thus, cold
      ischemia times are seldom monitored in non-breast cancer and non-gastroesophageal
      adenocarcinomas, and all tumor biospecimens are affected by chemical fixation.
      Although intended to preserve specimens for long-term storage, formalin fixation
      causes loss of genetic information through DNA damage. Herein, we describe a
      reference size matching, whole-genome amplification, and fluorescent labeling
      method for FFPE-derived DNA designed to improve chromosomal microarray results
      from suboptimal nucleic acids and salvage highly degraded samples. With this
      technological advance, whole-genome copy number analysis of tumor DNA can be
      reliably performed in the clinical laboratory for a wide variety of tissue
      conditions and tumor types.

PMID- 29471115
TI  - Targeted Next-Generation Sequencing Is a Sensitive Tool for Differential
      Diagnosis of Myelodysplastic Syndromes in Bone Marrow Trephines.
AB  - Myelodysplastic syndromes are hematological neoplasias in which immunohistologic
      examination of bone marrow trephines is important for a definite diagnosis.
      Unequivocal distinction from reactive bone marrow changes is, however, sometimes
      difficult. Because neoplastic clones in myelodysplastic syndrome carry mutations
      in recurrent genes, mutation detection by targeted next-generation sequencing may
      be a useful support for differential diagnosis. To elucidate the accuracy of this
      approach in the clinical diagnostic setting, we analyzed single and consecutive
      bone marrow trephines processed for immunohistologic examination from 145
      patients by targeted next-generation sequencing of 12 genes recurrently mutated
      in myelodysplastic syndromes. Of 110 patients with immunohistologic unequivocal
      diagnosis, 41 of 47 with myelodysplastic syndrome carried mutations. In 14
      consecutive samples available from these patients, remissions were accompanied by
      loss of mutations and ongoing disease with persisting mutations. Of 35 samples
      with indefinite immunohistologic appearance, 22 developed clinical unequivocal
      myelodysplastic syndrome in the further course, and 19 carried mutations already
      in the initial biopsy, which persisted in consecutive samples available from 13
      patients. No mutation was detected in any initial and consecutive sample of 13
      patients with indefinite immunohistologic appearance without clinical unequivocal
      myelodysplastic syndrome in the further course. We conclude that targeted next
      generation sequencing is an accurate tool for differential diagnosis of
      myelodysplastic syndrome in the clinical diagnostic setting.

PMID- 29471117
TI  - Coexistence of mcr-1, blaKPC-2 and two copies of fosA3 in a clinical Escherichia
      coli strain isolated from urine.
AB  - Here we report the first clinical Escherichia coli isolate co-harboring mcr-1,
      blaKPC-2 and two copies of fosA3 from China. The five plasmids of the isolate
      were completely sequenced and analyzed. Gene mcr-1 and blaKPC-2 were located on
      IncI2 and IncR plasmid, respectively. A variety of other resistance determinants
      such as fosA3 (two copies), blaCTX-M-123, blaOXA-1 and blaCTX-M-65 were also
      identified from the rest plasmids.

PMID- 29471116
TI  - Genetic populations and virulence factors of Helicobacter pylori.
AB  - Helicobacter pylori is a bacterium that has infected more than half of the human
      population worldwide. This bacterium is closely associated with serious human
      diseases, such as gastric cancer, and identifying and understanding factors that
      predict bacterial virulence is a priority. In addition, this pathogen shows high
      genetic diversity and co-evolution with human hosts. H. pylori population
      genetics, therefore, has emerged as a tool to track human demographic history. As
      the number of genome sequences available is increasing, studies on the evolution
      and virulence of H. pylori are gaining momentum. This review article summarizes
      the most recent findings on H. pylori virulence factors and population genetics.

PMID- 29471118
TI  - The dynamics of norovirus genotypes and genetic analysis of a novel recombinant
      GII.P12-GII.3 among infants and children in Bangkok, Thailand between 2014 and
      2016.
AB  - Norovirus (NoV) is the leading cause of viral acute gastroenteritis among all age
      groups in the world. We performed a molecular epidemiological study of the NoVs
      prevalent in Bangkok between November 2014 and July 2016 to investigate the
      emergence of new NoV variants in Thailand. A total of 332 stool specimens were
      collected from hospitalized pediatric patients with acute gastroenteritis in
      Bangkok, Thailand. NoVs were detected by real-time PCR. The genome of the N
      terminal/shell domain was amplified, the nucleotide sequence was determined, and
      phylogenetic analyses were performed. GII NoV was detected in 58 (17.5%) of the
      332 specimens. GII.17, a genotype strain prevalent from 2014 to mid-2015, was
      hardly detected and replaced by the GII.3 genotype strain. Entire genome
      sequencing followed by phylogenetic analysis of the GII.3 genotype strains
      indicated that they are new recombinant viruses, because the genome encoding ORF1
      is derived from a GII.12 genotype strain, whereas that encoding ORF2-3 is from a
      GII.3 genotype strain. The putative recombination breakpoints with the highest
      statistical significance were located around the border of 3Dpol and ORF2. The
      change in the prevalent strain of NoV seems to be linked to the emergence of new
      forms of recombinant viruses. These findings suggested that the swapping of the
      structural and non-structural proteins of NoV is a common mechanism by which new
      epidemic variants are generated in nature.

PMID- 29471119
TI  - Enediynes bearing polyfluoroaryl sulfoxide as new antiproliferative agents with
      dual targeting of microtubules and DNA.
AB  - A novel series of enediynes possessing pentafluorophenylsulfoxide have been
      developed. The innovative compounds possess antiproliferative activity against a
      broad panel of human cancer cells originating from breast, blood, lung, kidney,
      colon, prostate, pancreas or skin with IC50 ranging from 0.6 to 3.4 MUM. The
      antiproliferative activity of enediynes in darkness is associated to their
      ability to compromise microtubule network. In addition, exposure to UV leads to
      double-stranded DNA cleavage caused by the newly synthesized molecules reducing
      further their IC50 in nanomolar range against human tumor cells, including chemo
      resistant pancreatic cancer cells. Taken together, the examined data demonstrate
      that enediynes possessing pentafluorosulfoxide are promising molecules in the
      cancer therapy.

PMID- 29471120
TI  - The 4-N-acyl and 4-N-alkyl gemcitabine analogues with silicon-fluoride-acceptor:
      Application to 18F-Radiolabeling.
AB  - The coupling of gemcitabine with functionalized carboxylic acids using peptide
      coupling conditions afforded 4-N-alkanoyl analogues with a terminal alkyne or
      azido moiety. Reaction of 4-N-tosylgemcitabine with azidoalkyl amine provided 4-N
      alkyl gemcitabine with a terminal azido group. Click reaction with silane
      building blocks afforded 4-N-alkanoyl or 4-N-alkyl gemcitabine analogues suitable
      for fluorination. RP-HPLC analysis indicated better chemical stability of 4-N
      alkyl gemcitabine analogues versus 4-N-alkanoyl analogues in acidic aqueous
      conditions. The 4-N-alkanoyl gemcitabine analogues showed potent cytostatic
      activity against L1210 cell line, but cytotoxicity of the 4-N-alkylgemcitabine
      analogues was low. However, 4-N-alkanoyl and 4-N-alkyl analogues had comparable
      antiproliferative activities in the HEK293 cells. The 4-N-alkyl analogue with a
      terminal azide group was shown to be localized inside HEK293 cells by
      fluorescence microscopy after labelling with Fluor 488-alkyne. The [18F]4-N-alkyl
      or alkanoyl silane gemcitabine analogues were successfully synthesized using
      microscale and conventional silane-labeling radiochemical protocols. Preliminary
      positron-emission tomography (PET) imaging in mice showed the biodistribution of
      [18F]4-N-alkyl to have initial concentration in the liver, kidneys and GI tract
      followed by increasing signal in the bone.

PMID- 29471121
TI  - Diamine and PEGylated-diamine conjugates of triterpenic acids as potential
      anticancer agents.
AB  - A set of 18 amide derivatives of oleanolic or maslinic acid has been semi
      synthesised. Twelve were diamine conjugates at C-28 of these triterpenic acids
      and the other six were PEGylated-diamine derivatives. The cytotoxic effects of
      these 18 triterpenic derivatives in three cancer-cell lines (B16-F10, HT29, and
      Hep G2) have been assayed, and have been compared to three non-tumour cell lines
      of the same or a similar tissue (HPF, IEC-18, and WRL68). The cell viability
      percentages for the non-tumour HPF line for almost all diamine conjugates of the
      tested triterpenic acids ranged from 81% to 94%. The best cytotoxic results were
      achieved with the diamine conjugates of oleanolic or maslinic acid with the
      shortest and the longest diamine chain (IC50 values from 0.76 MUM to 1.76 MUM),
      on the B16-F10 cell line, being between 140- and 20-fold more effective than
      their corresponding precursors. Four diamine conjugates of these triterpenic
      acids showed apoptotic effects on treated cells of the B16-F10 line, with total
      apoptosis rates, relative to control, of between 73% and 90%. The DNA-histogram
      analysis revealed that all compounds tested produced cell-cycle arrest in B16-F10
      cells, increasing the number of these cells in the S phase. All the compounds
      analysed, except one, did not cause changes in mitochondrial-membrane potential
      during apoptosis of the B16-F10 cancer cells, suggesting an activation of the
      extrinsic apoptotic pathway for these compounds.

PMID- 29471122
TI  - Conformational mimetics of the alpha-methyl chalcone TUB091 binding tubulin:
      Design, synthesis and antiproliferative activity.
AB  - Based on the conformation of the alpha-methyl chalcone TUB091 in its complex with
      tubulin, a series of conformational mimetics have been designed and synthesized
      where the methyl group of the chalcone has been fused to phenyl ring B resulting
      in 1,2,3,4-tetrahydronaphthalen-2-yl aryl ketones. Among the synthesized
      compounds, the 5-amino-6-methoxy derivative, with a similar substitution pattern
      to that of TUB091, showed antiproliferative activity around 20 nM against tumor
      and endothelial cells. Tubulin binding experiments confirmed its binding to
      tubulin at the colchicine site with a Kb of 2.4 * 106 M-1 resulting in the
      inhibition of the in vitro assembly of purified tubulin. Moreover, based on the
      recently reported complex of combretastatin A4 (CA4) with tubulin, a comparative
      analysis of the binding mode of CA4 and the alpha-methyl chalcone to tubulin has
      been performed.

PMID- 29471123
TI  - Gold(III) bis(thiosemicarbazonate) compounds in breast cancer cells: Cytotoxicity
      and thioredoxin reductase targeting.
AB  - Gold(III) compounds have received increasing attention in cancer research. Three
      gold complexes of general formula [AuIIIL]Cl, where L is benzil
      bis(thiosemicarbazonate), compound 1, benzil bis(4-methyl-3-thiosemicarbazonate),
      compound 2, or benzil bis(4-cyclohexyl-3-thiosemicarbazonate), compound 3, have
      been synthesized and fully characterized, including the X-ray crystal structure
      of compound 3, confirming square-planar geometry around the gold(III) centre.
      Compound 1 showed moderate cytotoxicity and accumulation in MCF7 breast cancer
      cells but did not inhibit thioredoxin reductase (TrxR) activity and did not
      induce reactive oxygen species (ROS) production. Compound 2, the least cytotoxic,
      was found to be capable of modestly inhibiting TrxR activity and produced low
      levels of ROS in the MCF7 cell line. The most cytotoxic compound, 3, had the
      highest cellular accumulation and its distribution pattern showed a clear
      preference for the cytosol and mitochondria of MCF7 cells. It readily hampered
      intracellular TrxR activity leading to a dramatic alteration of the cellular
      redox state and to the induction of cell death.

PMID- 29471124
TI  - Methods and procedures for: A randomized double-blind study investigating dose
      dependent longitudinal effects of vitamin D supplementation on bone health.
AB  - The optimum dose of vitamin D and corresponding serum 25-hydroxyvitamin D (25OHD)
      concentration for bone health is still debated and some health practitioners are
      recommending doses well above the Canada/USA recommended Dietary Reference Intake
      (DRI). We designed a three-year randomized double-blind clinical trial
      investigating whether there are dose-dependent effects of vitamin D
      supplementation above the Dietary Reference Intake (DRI) on bone health. The
      primary aims of this study are to assess, whether supplementation of vitamin D3
      increases 1) volumetric bone mineral density measured by high-resolution
      peripheral quantitative computed tomography (HR-pQCT); 2) bone strength assessed
      by finite element analysis, and 3) areal bone mineral density by dual X-ray
      absorptiometry (DXA). Secondary aims are to understand whether vitamin D3
      supplementation improves parameters of bone microarchitecture, balance, physical
      function and quality of life. Participants are men and women aged 55-70 years,
      with women at least 5-years post-menopause. The intervention is daily vitamin D3
      supplementation doses of 400, 4000 or 10,000 IU. Participants not achieving
      adequate dietary calcium intake are provided with calcium supplementation, up to
      a maximum supplemental dose of 600 mg elemental calcium per day. Results from
      this three-year study will provide evidence whether daily vitamin D3
      supplementation with adequate calcium intake can affect bone density, bone
      microarchitecture and bone strength in men and women. Furthermore, the safety of
      high dose daily vitamin D3 supplementation will be explored.

PMID- 29471125
TI  - Biochar activation with exoenzymes induced by earthworms: A novel functional
      strategy for soil quality promotion.
AB  - The activation of biochar (carbonaceous material generated by pyrolysis of
      biomass) with extracellular enzymes generated from soil biological processes was
      studied via a 2-month microcosm using earthworms. The isolation of biochar
      particles (post-incubated biochar) from earthworm-treated soils allowed to
      confirm an enrichment of biochar with extracellular enzymes associated to
      biogeochemical (alkaline phosphatase, beta-glucosidase and arylsulfatase) and
      bioremediation pathways (carboxylesterase). The hydrolytic activity of this
      biochar incubated with earthworms was up to 8 times higher compared with that of
      control biochar (incubated in earthworm-free soils). More interestingly, the
      enzyme carboxylesterase was stabilized onto biochar surface as demonstrated by
      its unchanged hydrolytic activity after multiple water rinses of the post
      incubated biochar, and the remaining activity following heat stress. Moreover,
      this biochar-bound carboxylesterase activity was sensitive to inhibition by
      organophosphorus (23-100% of control activity) and methyl carbamate pesticides
      (37-57%), demonstrating that bioactivated biochar with carboxylesterases may
      inactivate these agrochemicals by providing stable ligands of enzymatic nature.

PMID- 29471126
TI  - Adsorption mechanism of extracellular polymeric substances from two bacteria on
      Ultisol and Alfisol.
AB  - The primary objective of this study was to identify the capacity and mechanism of
      extracellular polymeric substance (EPS) adsorption on soil colloids of Alfisol
      and Ultisol at different pH and ionic strengths. Two kinds of EPS were extracted
      from Bacillus subtilis and Pseudomonas fluorescens by centrifugation, and their
      adsorption on Ultisol and Alfisol was investigated using a batch adsorption
      experiment and attenuated total reflectance-Fourier transform infrared
      spectroscopy (ATR-FTIR). The average diameter of EPS from B. subtilis and P.
      fluorescens was 1825 and 1288 nm, respectively, and both the EPS were negatively
      charged. The zeta potentials of the two EPS became more negative with increasing
      solution pH from 3 to 8 and less negative with increasing ionic strength from 0
      to 80 mM. The maximum adsorption capacity of EPS-C and EPS-N on Alfisol was
      higher than that on Ultisol, whereas the maximum adsorption capacity of EPS-P on
      Alfisol was lower than that on Ultisol. The adsorption of EPS-C, EPS-N, and EPS-P
      of both the EPS on Ultisol and Alfisol decreased with increasing solution pH from
      3 to 8. Adsorption of EPS-C, EPS-N, and EPS-P of both the EPS on Alfisol
      significantly increased with increasing ionic strength from 0 to 10 mM, whereas
      it remained constant, slightly increased, or reduced, when the ionic strength was
      increased from 10 to 80 mM. The adsorption of EPS-C, EPS-N, and EPS-P on Ultisol
      slightly increased with increasing ionic strength from 0 to 80 mM. Saturation
      coverage determined by ATR-FTIR showed that adsorption of whole EPS on Ultisol
      was higher than that on Alfisol at pH 6 after 60 min. Thus, electrostatic force
      between EPS and soil colloids played an important role in EPS adsorption.
      Besides, proteins and phosphate groups in EPS also contributed to EPS adsorption
      on soil colloids.

PMID- 29471128
TI  - Spatiotemporal magnetic fields enhance cytosolic Ca2+ levels and induce actin
      polymerization via activation of voltage-gated sodium channels in skeletal muscle
      cells.
AB  - Cellular function is modulated by the electric membrane potential controlling
      intracellular physiology and signal propagation from a motor neuron to a muscle
      fiber resulting in muscle contraction. Unlike electric fields, magnetic fields
      are not attenuated by biological materials and penetrate deep into the tissue. We
      used complex spatiotemporal magnetic fields (17-70 mT) to control intracellular
      signaling in skeletal muscle cells. By changing different parameters of the
      alternating magnetic field (amplitude, inversion time, rotation frequency), we
      induced transient depolarization of cellular membranes leading to i) Na+ influx
      through voltage-gated sodium channels (VGSC), ii) cytosolic calcium increase, and
      iii) VGSC- and ryanodine receptor-dependent increase of actin polymerization. The
      ion fluxes occurred only, when the field was applied and returned to baseline
      after the field was turned off. The 30-s-activation-cycle could be repeated
      without any loss of signal intensity. By contrast, static magnetic fields of the
      same strength exhibited no effect on myotube Ca2+ levels. Mathematical modeling
      suggested a role for the alternating magnetic field-induced eddy current, which
      mediates a local change in the membrane potential triggering the activation of
      VGSC. These findings might pave the way for the use of complex magnetic fields to
      improve function of skeletal muscles in myopathies.

PMID- 29471127
TI  - Targeting CD14 on blood derived cells improves intracortical microelectrode
      performance.
AB  - Intracortical microelectrodes afford researchers an effective tool to precisely
      monitor neural spiking activity. Additionally, intracortical microelectrodes have
      the ability to return function to individuals with paralysis as part of a brain
      computer interface. Unfortunately, the neural signals recorded by these
      electrodes degrade over time. Many strategies which target the biological and/or
      materials mediating failure modes of this decline of function are currently under
      investigation. The goal of this study is to identify a precise cellular target
      for future intervention to sustain chronic intracortical microelectrode
      performance. Previous work from our lab has indicated that the Cluster of
      Differentiation 14/Toll-like receptor pathway (CD14/TLR) is a viable target to
      improve chronic laminar, silicon intracortical microelectrode recordings. Here,
      we use a mouse bone marrow chimera model to selectively knockout CD14, an innate
      immune receptor, from either brain resident microglia or blood-derived
      macrophages, in order to understand the most effective targets for future
      therapeutic options. Using single-unit recordings we demonstrate that inhibiting
      CD14 from the blood-derived macrophages improves recording quality over the 16
      week long study. We conclude that targeting CD14 in blood-derived cells should be
      part of the strategy to improve the performance of intracortical microelectrodes,
      and that the daunting task of delivering therapeutics across the blood-brain
      barrier may not be needed to increase intracortical microelectrode performance.

PMID- 29471129
TI  - Issues in estimating probability of detection of NDT techniques - A model
      assisted approach.
AB  - In order to successfully implement Damage Tolerance (DT) methodology for aero
      engines, Non-Destructive Testing (NDT) techniques are vital for assessing the
      remaining life of the component. Probability of Detection (POD), a standard
      measure of NDT reliability, is usually estimated as per MIL-HDBK-1823A standard.
      Estimation of POD of any NDT technique can be obtained by both experimental and
      model assisted methods. POD depends on many factors such as material, geometry,
      defect characteristics, inspection technique, etc. These requirements put
      enormous limitations on generating experimental POD curves and hence, Model
      Assisted Probability of Detection (MAPOD) curves are currently in vogue. In this
      study, MAPOD approaches were demonstrated by addressing various issues related to
      selection of crack sizes distribution, challenges involved in censoring and
      regression, estimation of distribution parameters, etc. Ultrasonic testing on
      volumetric defects has been identified as a platform to discuss the challenges
      involved. A COMSOL Multiphysics based FEM numerical model developed to simulate
      ultrasonic response from a Ti-6Al-4V cylindrical block has been validated
      experimentally. Further, the individual ultrasonic response from various Flat
      Bottom Hole (FBH) defects following lognormal distribution has been generated
      using the numerical model. a90/95 (detecting a flaw with 90% probability and 95%
      confidence) value obtained from POD curve showed that the POD value increased
      with an increase in decision threshold.

PMID- 29471130
TI  - Effect of e-cigarette advertisement exposure on intention to use e-cigarettes in
      adolescents.
AB  - INTRODUCTION: With the growth of electronic cigarettes use, curiosity about and
      experimentation with these products has increased among adolescents. The purpose
      of the present study was to evaluate the moderating effect of e-cigarette
      advertisement (ad) exposure on the relation between perceptions of use and
      intentions to use in youth. METHODS: Multiple regression analyses utilizing data
      from the 2014 National Youth Tobacco Survey (N = 17,286) were used to evaluate
      the effect of ad exposure, perceived harmfulness, barriers, and benefits of e
      cigarette use on intentions to use among youth who had never used e-cigarettes.
      RESULTS: Models for non-smokers accounted for 15.5% of the variance in intention
      to use (R2 = 0.155, F (15) = 187.0, p < 0.001). Results demonstrate that an
      increase in the number of exposures to e-cigarette ads was associated with an
      increase in intent to use (b = 0.039, t = 7.4, p < 0.001). Models also
      demonstrated significant interactions between ad exposure and perceptions of use
      on future intention to use. For smokers, models explained 11.1% of the variance
      in intention to use (R2 = 0.111, F (15) = 3.1, p < 0.001). Ad exposure had a non
      significant effect on intention to use e-cigarettes (b = -0.010, t = -0.2, p =
      0.859). In smokers, ad exposure did not significantly affect the association
      between perceptions of use and intention to use. CONCLUSIONS: Ads are most
      effective at attracting non-smoking youth as new users rather than promoting
      product switching in young cigarette smokers.

PMID- 29471131
TI  - Aerobic and strength training induce changes in oxidative stress parameters and
      elicit modifications of various cellular components in skeletal muscle of aged
      rats.
AB  - Skeletal muscle aging is associated with loss of mass, function, and strength-a
      condition known as sarcopenia. It has been reported that sarcopenia can be
      attenuated by physical exercise. Therefore, we investigated whether 2 different
      physical exercise protocols could modulate and induce changes in oxidative and
      inflammatory parameters, as well as in BDNF and DNA repair enzyme levels in
      skeletal muscle tissue of aged rats. Aging Wistar rats performed treadmill or
      strength training for 50 min 3 to 4 times a week for 8 weeks. Strength training
      decreased 2',7'-dichlorofluorescein (DCFH) oxidation (P = 0.0062); however,
      nitric oxide, protein deglycase DJ-1, and tumor necrosis factor alpha (TNF-alpha)
      levels increased after aerobic training (P = 0.04, P = 0.027 and P = 0.009,
      respectively). Both exercise protocols increased superoxide dismutase (SOD) and
      catalase (CAT) activity (P = 0.0017 and P = 0.0326) whereas the activity of
      glutathione (GSH) (P = 0.0001) was decreased. Brain-derived neurotropic factor
      (BDNF) levels were not affected by exercise, but 8-oxoguanine glycosylase (OGG1)
      decreased after strength training (P = 0.0007). In conclusion, oxidative
      parameters showed that skeletal muscle adapt to increased ROS levels, reducing
      the risk of free radical damage to the tissue after both exercise protocols.
      These results show that the effects of physical exercise on skeletal muscle are
      mediated in an exercise type-dependent manner.

PMID- 29471132
TI  - High-intensity body weight training is comparable to combined training in changes
      in muscle mass, physical performance, inflammatory markers and metabolic health
      in postmenopausal women at high risk for type 2 diabetes mellitus: A randomized
      controlled clinical trial.
AB  - OBJECTIVE: This study compared the effects of 12 weeks of high-intensity interval
      body weight training (HIBWT) with combined training (COMT; aerobic and resistance
      exercises on body composition, a 6-minute walk test (6MWT; physical performance),
      insulin resistance (IR) and inflammatory markers in postmenopausal women (PW) at
      high risk of type 2 diabetes mellitus (TDM2). METHODS: In this randomized
      controlled clinical study, 16 PW at high risk of TDM2 were randomly allocated
      into two groups: HIBWT (n = 8) and COMT (n = 8). The HIBWT group performed a
      training protocol (length time ~28 min) consisting of ten sets of 60 s of high
      intensity exercise interspersed by a recovery period of 60 s of low intensity
      exercise. The COMT group performed a training protocol (length time ~60 min)
      consisting of a 30 min walk of moderate intensity following by five resistance
      exercises. All training sessions were performed in the university gym facility
      three days a week (no consecutive days) for 12 weeks. All outcomes (body
      composition, muscle function, and IR and inflammatory markers) were assessed at
      the baseline and at the end of the study. RESULTS: Both groups increased (P <
      0.05) muscle mass index (MMI), 6MWT, and interleukin 1 receptor antagonist and
      decreased fasting glucose, glycated hemoglobin, Insulin, HOMA-IR, and monocyte
      chemoattractant protein-1 (trend, P = 0.056). HIBWT effects were
      indistinguishable (P > 0.05) from the effects of COMT. There was a significant (P
      < 0.05) interaction of time by the group in muscle strength, indicating that only
      the COMT increased the muscle strength. CONCLUSIONS: This study suggests that
      changes in HOMA, IL-1ra, 6MWT, and MMI with HITBW are similar when compared to
      COMT in PW at high risk of TDM2. TRIAL REGISTRATION: The patients were part of a
      12-week training study (ClinicalTrials.gov Identifier: NCT03200639).

PMID- 29471133
TI  - Neural network for nonsmooth pseudoconvex optimization with general convex
      constraints.
AB  - In this paper, a one-layer recurrent neural network is proposed for solving a
      class of nonsmooth, pseudoconvex optimization problems with general convex
      constraints. Based on the smoothing method, we construct a new regularization
      function, which does not depend on any information of the feasible region. Thanks
      to the special structure of the regularization function, we prove the global
      existence, uniqueness and "slow solution" character of the state of the proposed
      neural network. Moreover, the state solution of the proposed network is proved to
      be convergent to the feasible region in finite time and to the optimal solution
      set of the related optimization problem subsequently. In particular, the
      convergence of the state to an exact optimal solution is also considered in this
      paper. Numerical examples with simulation results are given to show the
      efficiency and good characteristics of the proposed network. In addition, some
      preliminary theoretical analysis and application of the proposed network for a
      wider class of dynamic portfolio optimization are included.

PMID- 29471134
TI  - Citrobacter freundii impairs the phosphoryl transfer network in the gills of
      Rhamdia quelen: Impairment of bioenergetics homeostasis.
AB  - The precise coupling of spatially separated intracellular adenosine triphosphate
      (ATP)-producing and ATP-consuming, catalyzed by creatine kinase (CK), adenylate
      kinase (AK), and pyruvate kinase (PK), is a critical process in the bioenergetics
      of tissues with high energy demand, such as the branchial tissue. The effects of
      Citrobacter freundii infection on gills remain poorly understood, limited only to
      histopathological studies. Thus, the aim of this study was to evaluate whether
      experimental infection by C. freundii impairs the enzymes of the phosphoryl
      transfer network in gills of silver catfish (Rhamdia quelen). The CK (cytosolic
      and mitochondrial) and AK activities decreased in infected compared to uninfected
      animals, while the PK activity did not differ between groups. The gill
      histopathology of infected animals revealed extensive degeneration with fusion
      and necrosis of secondary lamellae, detachment of superficial epithelium,
      aneurysm, vessel congestion and inflammatory process. Based on these evidences,
      the inhibition and absence of an efficient communication between CK compartments
      caused the impairment of the branchial bioenergetics homeostasis, which was not
      compensated by the augmentation on branchial AK activity in an attempt to restore
      energy homeostasis. In summary, these alterations contribute to disease
      pathogenesis linked to branchial tissue in animals infected with C. freundii.

PMID- 29471135
TI  - Murine model for the evaluation of candiduria caused by Candida tropicalis from
      biofilm.
AB  - To evaluate the pathophysiology of catheter-associated candiduria, the bladders
      of female mice were infected with Candida tropicalis. One group was implanted
      with a catheter fragment with preformed biofilm by cystotomy technique, while
      another group received, in separate, a sterile catheter fragment and a
      correspondent yeast suspension. The bladder tissues were examined by
      histopathology and the quantity of colony forming units was evaluated. All the
      animals presented inflammation and the presence of C. tropicalis was observed in
      the tissue within 72 h of the introduction of biofilm, while 75% of the mice
      remained infected after 144 h. However, only 50% of animals from the group
      infected with C. tropicalis in suspension (planktonic yeasts), exhibited such
      signs of infection over time. The cystotomy technique is therefore viable in
      mice, and is an effective model for evaluating the pathogenesis of candiduria
      from catheter biofilms. The model revealed the potential of C. tropicalis
      infectivity and demonstrated more effective evasion of the host response in
      biofilm form than the planktonic yeast.

PMID- 29471136
TI  - Post-weaning piglets fed with different levels of fungal mycotoxins and spray
      dried porcine plasma have improved weight gain, feed intake and reduced diarrhea
      incidence.
AB  - Mycotoxins are responsible for economic losses in the swine production industry,
      especially during post-weaning, when piglets are physiologically immature. Spray
      dried porcine plasma (SDPP), added to pig diets, may help reduce losses due to
      mycotoxins. This work investigates the effects of SDPP in post-weaning piglets
      fed with diets containing natural contaminants or with more contaminants (co
      contamination by mycotoxins). Fifty-six castrated weaned piglets were used in a
      randomized 2 (0 and 6% of SDPP) x 2 (natural contamination or co-contamination
      with mycotoxin) factorial design, with seven experimental units of two piglets
      each. The natural contaminants were 0.95 MUg/kg aflatoxins +450 MUg/kg
      fumonisins. The co-contaminated diet contained 300 MUg/kg aflatoxins +8000 MUg/kg
      fumonisins. Animals were fed 15 days with experimental diets. Feed intake, weight
      gain, feed efficiency, diarrhea incidence, and economic feasibility of SDPP
      treatement were evaluated in three periods of five days each. There was no
      interaction (P < 0.05) between mycotoxins levels and SDPP. Feed intake, weight
      gain and feed efficiency were higher (P < 0.05) in diets supplemented with SDPP.
      Animals fed with SDPP showed lower (P < 0.05) diarrhea incidence in the 1-10 day
      and 1-15 day periods. The experimental dose of mycotoxins reduced (P < 0.05)
      weight gain at 11-15 days. SDPP proved to be economical feasible over the total
      experimental period (1-15 days). Spray-dried plasma improved weight gain, feed
      intake and reduced diarrhea incidence in piglets post-weaning, but did not
      correlate with various levels of mycotoxins.

PMID- 29471137
TI  - Mucosal and systemic responses of immunogenic vaccines candidates against enteric
      Escherichia coli infections in ruminants: A review.
AB  - Innumerable Escherichia coli of animal origin are identified, which are of
      economic significance, likewise, cattle, sheep and goats are the carrier of
      enterohaemorrhagic E. coli, which are less pathogenic, and can spread to people
      by way of direct contact and through the contamination of foodstuff or portable
      drinking water, causing serious illness. The immunization of ruminants has been
      carried out for ages and is largely acknowledged as the most economical and
      maintainable process of monitoring E. coli infection in ruminants. Yet, only a
      limited number of E. coli vaccines are obtainable. Mucosal surfaces are the most
      important ingress for E. coli and thus mucosal immune responses function as the
      primary means of fortification. Largely contemporary vaccination processes are
      done by parenteral administration and merely limited number of E. coli vaccines
      are inoculated via mucosal itinerary, due to its decreased efficacy.
      Nevertheless, aiming at maximal mucosal partitions to stimulate defensive
      immunity at both mucosal compartments and systemic site epitomises a prodigious
      task. Enormous determinations are involved in order to improve on novel mucosal
      E. coli vaccines candidate by choosing apposite antigens with potent
      immunogenicity, manipulating novel mucosal itineraries of inoculation and
      choosing immune-inducing adjuvants. The target of E. coli mucosal vaccines is to
      stimulate a comprehensive, effective and defensive immunity by specifically
      counteracting the antibodies at mucosal linings and by the stimulation of
      cellular immunity. Furthermore, effective E. coli mucosal vaccine would make
      vaccination measures stress-free and appropriate for large number of inoculation.
      On account of contemporary advancement in proteomics, metagenomics, metabolomics
      and transcriptomics research, a comprehensive appraisal of the immeasurable genes
      and proteins that were divulged by a bacterium is now in easy reach. Moreover,
      there exist marvellous prospects in this bourgeoning technologies in
      comprehending the host bacteria affiliation. Accordingly, the flourishing
      knowledge could massively guarantee to the progression of immunogenic vaccines
      against E. coli infections in both humans and animals. This review highlight and
      expounds on the current prominence of mucosal and systemic immunogenic vaccines
      for the prevention of E. coli infections in ruminants.

PMID- 29471138
TI  - Antibacterial activities of tannic acid against isolated ruminal bacteria from
      sheep.
AB  - This present study was conducted to evaluate the antimicrobial effects of tannic
      acid (TA) against isolated ruminal bacteria from adult sheep. Rumen samples were
      collected from two (2) adults sheep, and a total of nine (9) ruminal bacteria
      were isolated from the sample. The sensitivity of the ruminal bacteria isolates
      to 0.63, 1.25, 2.50, 5.00 and 10.00 mg TA/mL of growth medium was determined
      using clearance zone (CZ) of Kirby-Bauer disc diffusion susceptibility test.
      There was observable increase in the sensitivity of all bacterial isolates as the
      level of TA increases. Not all bacterial isolates have the capacity to tolerate
      more than 1.25 mg TA/mL. The result shows that only 20% of the bacterial isolates
      had the capacity to tolerate 0.63 and 1.25 mg of tannic acid per liter. This
      concentration of tannic acid would be equivalent to 2% tannin in the diet of
      ruminant. Our findings shows that increase in concentration of tannic acid
      completely inhibited the ruminal bacteria from the sheep rumen.

PMID- 29471139
TI  - TLR2/MyD88/NF-kappaB signaling pathway regulates IL-1beta production in DF-1
      cells exposed to Mycoplasma gallisepticum LAMPs.
AB  - Mycoplasma gallisepticum (M. gallisepticum) is one of the most important
      pathogens that cause chronic respiratory disease in chickens. M. gallisepticum
      derived lipid-associated membrane proteins (LAMPs) are thought to be one of the
      major factors in mycoplasma pathogenesis and are potent inducers of the host
      innate immune response. However, the interaction of pathogenic M. gallisepticum
      derived LAMPs with Toll-like receptors (TLRs) and the signaling pathways
      responsible for activating inflammation and NF-kappaB have not been fully
      elucidated. In this study, we found that IL-1beta expression was induced in DF-1
      cells stimulated with M. gallisepticum LAMPs. Subcellular localization
      experiments using immunofluorescence assays (IFAs) showed p65 translocation from
      the cytoplasm to the nucleus in DF-1 cells following stimulation with M.
      gallisepticum LAMPs. Phosphorylation of p65 was detected in LAMP-stimulated DF-1
      cells. Treatment with an NF-kappaB-specific inhibitor showed that NF-kappaB is
      required for M. gallisepticum LAMP-induced IL-1beta expression. In addition, the
      results indicated that TLR2 and myeloid differentiation primary-response protein
      88 (MyD88)-dependent signaling pathways were involved in the activation of NF
      kappaB by M. gallisepticum LAMPs. Together, these results provide evidence that
      M. gallisepticum LAMPs activate IL-1beta production through the NF-kappaB pathway
      via TLR2 and MyD88.

PMID- 29471141
TI  - The morphological and molecular mechanisms of epithelial/endothelial-to
      mesenchymal transition and its involvement in atherosclerosis.
AB  - Cell transdifferentiation occurs during cardiovascular development or remodeling
      either as a pathologic feature in the progression of disease or as a response to
      injury. Endothelial-to-Mesenchymal Transition (EndMT) is a process that is
      classified as a specialized form of Epithelial-to-Mesenchymal Transition (EMT),
      in which epithelial cells lose their epithelial characteristics and gain a
      mesenchymal phenotype. During transdifferentiation, cells lose both cell-cell
      contacts and their attachment to the basement membrane. Subsequently, the shape
      of the cells changes from a cuboidal to an elongated shape. A rearrangement of
      actin filaments facilitates the cells to become motile and prime their migration
      into the underlying tissue. EMT is a key process during embryonic development,
      wound healing and tissue regeneration, but has also been implicated in
      pathophysiological processes, such organ fibrosis and tumor metastases. EndMT has
      been associated with additional pathophysiological processes in cardiovascular
      related diseases, including atherosclerosis. Recent studies prove a significant
      role for EndMT in the progression and destabilization of atherosclerotic plaques,
      as a consequence of EndMT-derived fibroblast infiltration and the increased
      secretion of matrix metalloproteinase respectively. In this review we will
      discuss the essential molecular and morphological mechanisms of EMT and EndMT,
      along with their common denominators and key differences. Finally, we will
      discuss the role of EMT/EndMT in developmental and pathophysiological processes,
      focusing on the potential role of EndMT in atherosclerosis in more depth.

PMID- 29471140
TI  - Activation of endothelial TrkB receptors induces relaxation of resistance
      arteries.
AB  - While brain-derived neurotrophic factor (BDNF) was previously reported to induce
      relaxation of conduit artery, whether the BDNF/TrkB (tropomyosin-related kinase)
      pathway is involved in the tone control of resistance arteries is not known. This
      study investigated TrkB receptors levels/localization and the vasomotor effect of
      the TrkB receptor agonist LM22A-4 in isolated third-order mesenteric arteries
      from rats. Immunostaining revealed the presence of both full-length and truncated
      TrkB receptors, especially at the endothelial level. By using wire myography,
      LM22A-4 induced vascular relaxation that was significantly decreased by
      cyclotraxin B as a non-competitive TrkB antagonist and fully prevented by
      endothelium removal. Inhibitors of NO, EDHF, PGI2 production and the PI3K/Akt
      pathways separately reduced LM22A-4 induced-relaxation. By contrast, inhibition
      of Raf/MEK, PLCgamma and CaM/CaMKII pathways did not change the relaxant effect
      of LM22A-4. Interestingly, BDNF also induced an endothelium and TrkB-dependent
      relaxation. These results indicate that endothelial TrkB activation results in
      the relaxation of resistance vessels via PI3K/Akt-induced eNOS phosphorylation
      and production of EDHF and PGI2. These data are consistent with the contribution
      of the endothelial BDNF/TrkB pathway to the regulation of peripheral vascular
      tone. They also validate the use of LM22A-4 as a reliable pharmacological agent
      for studying the vascular effect of BDNF.

PMID- 29471142
TI  - Hair analysis when external contamination is in question: A review of practical
      approach for the interpretation of results.
AB  - Despite having been extensively discussed over the last decade, the
      differentiation between systemic exposure and external contamination still
      continues to be one of the limitations of hair testing for drugs. For this
      reason, we consider it worthwhile to re-state some basic principles in this short
      review. Various studies investigating a diversity of wash protocols, most using
      artificially contaminated hair with cocaine, have been valuable in evaluating
      wash efficacy and in understanding the incorporation of drugs in hair. However,
      assessments of wash efficacy made with real hair samples, as opposed to
      artificially contaminated samples, provide a different perspective, and
      demonstrate how rarely external contamination affects the interpretation of
      results. Data from a large number of hair samples from crack cocaine users,
      confirmed the usefulness of our protocol to remove most of the externally
      deposited cocaine. The data showed that hair levels of cocaine and
      benzoylecgonine in crack cocaine users were overall high with ratio of
      benzoylecgonine to cocaine in all samples above 0.1. The wash residue
      concentrations of cocaine ranged from not detected to 21ng/mg with a median of
      0.5ng/mg. Cocaine was detected in the wash residue in 105 out of 138 samples. The
      wash to hair cocaine ratio ranged from not detected to 0.36 with a median of
      0.02. The wash to hair cocaine ratios were below 0.07 in 133 cases. The five
      cases that produced wash to hair ratios above 0.1, one sample was at 0.11, three
      at 0.13 and one at 0.36, possibly because these cases were at the lower end of
      cocaine levels, however, we could not rule out that the hair was contaminated.
      Whilst it is not possible to differentiate between the drug extracted from the
      hair and the drug attached to the outside of the hair, we can compare levels of
      drug in the wash residue with levels detected in the hair sample. In addition,
      further diagnostic criteria must be applied to minimise potential misdiagnosis of
      external contamination. When drugs are detected in hair, individuals have clearly
      been in an environment where drugs are present, but it is only on rare occasions
      that it is unclear whether this is the result of drug use or of external
      contamination, and, in those cases, the results of testing need to be interpreted
      in the light of corroborating evidence from clinical data or social context.

PMID- 29471143
TI  - Transdermal delivery of vitamin K using dissolving microneedles for the
      prevention of vitamin K deficiency bleeding.
AB  - Vitamin K deficiency within neonates can result in vitamin K deficiency bleeding.
      Ensuring that newborns receive vitamin K is particularly critical in places where
      access to health care and blood products and transfusions is limited. The World
      Health Organization recommends that newborns receive a 1 mg intramuscular
      injection of vitamin K at birth. Evidence from multiple surveillance studies
      shows that the introduction of vitamin K prophylaxis reduces the incidence of
      vitamin K deficiency bleeding. Despite these recommendations, coverage of vitamin
      K prophylactic treatment in low-resource settings is limited. An intramuscular
      injection is the most common method of vitamin K administration in neonates. In
      low- and middle-income countries, needle sharing may occur, which may result in
      the spread of bloodborne diseases. The objective of our study was to investigate
      the manufacture of microneedles for the delivery of vitamin K. Following
      microneedle fabrication, we performed insertion studies to assess the
      microneedle's mechanical properties. Results indicate that vitamin K in a
      microneedle array was successfully delivered in vitro across neonatal porcine
      skin with 1.80 +/- 0.08 mg delivered over 24 h. Therefore, this initial study
      shows that microneedles do have the potential to prevent vitamin K deficiency
      bleeding. Future work will assess delivery of vitamin K in microneedle array in
      vivo.

PMID- 29471144
TI  - Intestinal absorption and activation of decitabine amino acid ester prodrugs
      mediated by peptide transporter PEPT1 and enterocyte enzymes.
AB  - Decitabine (DAC), a potent DNA methyltransferase (DNMT) inhibitor, has a limited
      oral bioavailability. Its 5'-amino acid ester prodrugs could improve its oral
      delivery but the specific absorption mechanism is not yet fully understood. The
      aim of this present study was to investigate the in vivo absorption and
      activation mechanism of these prodrugs using in situ intestinal perfusion and
      pharmacokinetics studies in rats. Although PEPT1 transporter is pH dependent,
      there appeared to be no proton cotransport in the perfusion experiment with a
      preferable transport at pH 7.4 rather than pH 6.5. This suggested that the
      transport was mostly dependent on the dissociated state of the prodrugs and the
      proton gradient might play only a limited role. In pH 7.4 HEPES buffer, an
      increase in Peff was observed for L-val-DAC, D-val-DAC, L-phe-DAC and L-trp-DAC
      (2.89-fold, 1.2-fold, 2.73-fold, and 1.90-fold, respectively), compared with the
      parent drug. When co-perfusing the prodrug with Glysar, a known substrate of
      PEPT1, the permeabilities of the prodrugs were significantly inhibited compared
      with the control. To further investigate the absorption of the prodrugs, L-val
      DAC was selected and found to be concentration-dependent and saturable,
      suggesting a carrier-mediated process (intrinsic Km: 7.80 +/- 2.61 mM) along with
      passive transport. Determination of drug in intestinal homogenate after perfusion
      further confirmed that the metabolic activation mainly involved an intestinal
      first-pass effect. In a pharmacokinetic evaluation, the oral bioavailability of L
      val-DAC, L-phe-DAC and L-trp-DAC were nearly 1.74-fold, 1.69-fold and 1.49-fold
      greater than that of DAC. The differences in membrane permeability and oral
      bioavailability might be due to the different stability in the intestinal lumen
      and the distinct PEPT1 affinity which is mainly caused by the stereochemistry,
      hydrophobicity and steric hindrance of the side chains. In summary, the detailed
      investigation of the absorption mechanism by in vivo intestinal perfusion and
      pharmacokinetic studies showed that the prodrugs of DAC exhibited excellent
      permeability and oral bioavailability, which might be attributed to a hybrid
      (partly PEPT1-mediated and partly passive) transport mode and a rapid activation
      process in enterocytes.

PMID- 29471145
TI  - Establishment of an evaluation method to detect drug distribution in hair
      follicles.
AB  - Development of an appropriate method to evaluate drug disposition or targeting
      ability in hair follicles (HFs) is urgently needed in order to develop useful
      pharmaceutical products with pharmacological effects in HFs. In the present
      study, a cyanoacrylate biopsy (CB) method was used to measure drug disposition in
      HFs using a model hydrophilic drug, caffeine (CAF), and a lipophilic drug, 4
      butylresorcinol (BR), in excised porcine skin. As a result, the height of HF
      replicas and the recovery ratio decreased with an increase in the application
      times of the CB method. HF replicas with a length of approximately 175 um were
      obtained using a single application of the CB method. Drug distribution in the HF
      was detected even 5 min after topical application regardless of the lipophilicity
      of the drugs, although no drug disposition was observed in the deeper layers of
      the stratum corneum at the same time (5 min). Furthermore, significantly higher
      amounts of BR were observed in the stratum corneum and HF, compared with those of
      CAF. These results suggested that the CB method could be useful to evaluate the
      safety and efficacy as well as the disposition of topically applied chemicals,
      especially for HF-targeting drugs.

PMID- 29471146
TI  - The impact of feedback valence and communication style on intrinsic motivation in
      middle childhood: Experimental evidence and generalization across individual
      differences.
AB  - Prior research among adolescents and emerging adults has provided evidence for
      the beneficial effects of positive (relative to negative) feedback and an
      autonomy-supportive (relative to a controlling) communication style on students'
      intrinsic motivation. Unfortunately, similar experimental research in middle
      childhood is lacking. Moreover, little attention has been paid to the question of
      whether individual differences in personality and perceived parenting play a role
      in these effects. In the current experimental study (N = 110; Mage = 10.71
      years), children completed puzzles at school under one of four experimental
      conditions, thereby crossing normative feedback valence (i.e., positive vs.
      negative) with communication style (i.e., autonomy supportive vs. controlling).
      Prior to the experiment, children filled out questionnaires tapping into the Big
      Five personality traits and into perceived maternal autonomy support and
      psychological control. After the experimental induction, children rated several
      motivational constructs (i.e., intrinsic motivation and need-based experiences).
      In addition, their voluntary behavioral persistence in a subsequent challenging
      puzzle task was recorded objectively. Providing positive normative feedback in an
      autonomy-supportive way yielded the most favorable motivational outcomes. Both
      feedback valence and communication style yielded an independent impact on
      children's experiences of competence and autonomy during task engagement, which
      in turn helped to explain children's elevated intrinsic motivation, as reflected
      by their perceived interest and behavioral persistence. A few effects were
      moderated by children's perceived parenting and personality traits, but the
      number of interactions was limited. The discussion focuses on the motivating role
      of positive normative feedback and an autonomy-supportive communication style for
      children.

PMID- 29471148
TI  - Photonic technology for the treatments of venous and arterial ulcers: Case
      report.
AB  - In this report, we report a case study on a 50-year-old male patient with
      different chronic wounds, such as venous ulcer and arterial ulcer in both legs.
      These wounds have persisted for more than 10 years, despite the different
      treatments applied, including, different dressings, hyperbaric camera, as well as
      the used of several medicines of oral and topical application. The case is
      addressed with the aim to evaluate if treatment that uses combined techniques
      such as low level laser therapy (LLLT), photodynamic therapy and cellulose
      membrane is able to improve healing and reduction of time of treatment in those
      types of chronic wounds. The results show the clinical protocol is effective for
      the healing of arterial and venous ulcers and can be considered as a promising
      possibility.

PMID- 29471147
TI  - Blue light versus red light for photodynamic therapy of basal cell carcinoma in
      patients with Gorlin syndrome: A bilaterally controlled comparison study.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a non-scarring alternative for treating
      basal cell carcinoma (BCC) in patients with Basal Cell Nevus Syndrome (BCNS),
      also known as Gorlin syndrome. In Europe, red light (635 nm) is the predominant
      source for PDT, whereas in the United States blue light (400 nm) is more widely
      available. The objective of this study was to conduct a head-to-head comparison
      of blue light and red light PDT in the same BCNS patients. METHODS: In a pilot
      study of three patients with 141 BCC lesions, 5-aminolevulinate (20% solution)
      was applied to all tumors. After 4 h, half of the tumors were illuminated with
      blue light and the remainder with red light. To ensure safety while treating this
      many tumors simultaneously, light doses were escalated gradually. Six treatments
      were administered in three biweekly sessions over 4 months, with a final
      evaluation at 6 months. Tumor status was documented with high-resolution
      photographs. Persistent lesions were biopsied at 6 months. RESULTS: Clearance
      rates after blue light (98%) were slightly better than after red light (93%),
      with blue light shown to be statistically non-inferior to red light. Eight
      suspicious lesions were biopsied, 5 after red light (5/5 were BCC) and 3 after
      blue light (1 was BCC). Blue light PDT was reportedly less painful. CONCLUSION:
      Blue light and red light PDT appear to be equally safe and perhaps equally
      effective for treating BCC tumors in BCNS patients. Further studies to evaluate
      long-term clearance after blue light PDT are needed.

PMID- 29471149
TI  - Is adjunctive photodynamic therapy more effective than scaling and root planing
      alone in the treatment of periodontal disease in hyperglycemic patients? A
      systematic review.
AB  - BACKGROUND: To assess the impact of scaling and root planing (SRP) with and
      without adjunct photodynamic therapy (PDT) in the treatment of periodontal
      disease (PD) in hyperglycemic patients. METHODS: Databases (MEDLINE, EMBASE; and
      CENTRAL) were searched up to December 2017. The addressed PICO question was:
      "What is the effectiveness of adjunctive PDT to non-surgical periodontal
      treatment by means of clinical periodontal and glycemic parameters in
      hyperglycemic patients?" RESULTS: Four clinical trials and 1 experimental study
      were included. Energy fluence, power output, power density and duration of
      irradiation were 2.79 J per square centimeters (J cm-2), 150 milliwatts (mW), 428
      milliwatts per square centimeters (mW/cm2) and 133 s (s) respectively. All
      studies reporting clinical periodontal and metabolic parameters, showed that aPDT
      was effective in the treatment of periodontal inflammation in hyperglycemic
      patients at follow-up. When compared with SRP alone, none of the studies showed
      additional benefits of PDT as compared to SRP alone at follow up. Three studies
      showed no influence of SRP with or without aPDT on HbA1c levels. One study showed
      a significant reduction of HbA1c levels in adjunctive aPDT as compared to SRP
      alone at follow-up. CONCLUSION: It remains debatable whether adjunctive PDT as
      compared to SRP is effective in the treatment of periodontal inflammation and
      reduction of HbA1c levels in hyperglycemic patients.

PMID- 29471150
TI  - Comprehensive virome analysis reveals the complexity and diversity of the viral
      spectrum in pediatric patients diagnosed with severe and mild hand-foot-and-mouth
      disease.
AB  - The management of hand-foot-and-mouth disease(HFMD) epidemic is difficult due to
      the frequent emergence of non-EV71 and non-CVA16 enteroviruses and some cases
      testing negative for HFMD-associated causative agents. To clarify the virus
      spectrum of mild and severe HFMD, a comprehensive virome analysis of 238 samples
      was performed using next-generation sequencing (NGS). The data revealed total
      thirteen mammalian- and plant- virus families and diverse viral populations
      including enteroviruses, common respiratory viruses, diarrhea-related viruses,
      plant viruses and anelloviruses. A total of 18 viruses from 7 virus families were
      identified in severe cases, versus 37 viruses from 12 virus families in mild
      cases. Moreover, complicated mixed-infections of enteroviruses with common
      respiratory viruses were mainly found in severe cases(P = 0.013), while diarrhea
      related viruses were mainly found in mild cases(P < 0.001). This study provides
      the preliminary understanding of viromes both in mild and severe cases, which may
      benefit the detection of etiologic agents and prevention of HFMD.

PMID- 29471151
TI  - The herbicide atrazine affects sperm quality and the expression of antioxidant
      and spermatogenesis genes in zebrafish testes.
AB  - The herbicide atrazine (ATZ) is used worldwide in the control of annual grasses
      and broad-leaved weeds. The present study evaluated sperm quality parameters in
      zebrafish Danio rerio after 11-day exposure to nominal ATZ concentrations of 2,
      10, and 100 MUg L-1. All ATZ concentrations caused a decrease in motility,
      mitochondrial functionality, and membrane integrity, as measured using
      conventional microscopy or fluorescence microscopy with specific probes. The DNA
      integrity of sperm was not affected. The levels of expression of genes related to
      spermatogenesis, antioxidant defenses, and DNA repair were also investigated
      using RT-qPCR. The ATZ caused transcriptional repression of the spermatogenesis
      related genes SRD5A2 and CFTR, the antioxidant defense genes SOD2 and GPX4B, and
      the DNA repair gene XPC. This is the first study to show that environmentally
      relevant concentrations of ATZ significantly affect the sperm quality in fish,
      possibly resulting in reduced fertility rates. In addition, we showed that the
      repression of genes related to spermatogenesis and cellular defense could be part
      of the mechanisms involved in the ATZ toxicity in the testes of male fish.

PMID- 29471152
TI  - Carpal tunnel release with a new mini-incision approach versus a conventional
      approach, a retrospective cohort study.
AB  - PURPOSE: We have make use of a new method to perform carpal tunnel release (CTR)
      through a 1.5-2.0 cm long incision The aim of this study is to introduce this
      method and to compare the effectiveness and safety of this approach to the
      conventional one. METHODS: We included consecutive patients diagnosed with
      primary carpal tunnel syndrome (CTS) who had CTR from January 2015 to September
      2016. A total of 85 patients were included in our study. Among them, 42 patients
      with mini-incision approach were enrolled in group A, and the other 43 patients
      with conventional approach were enrolled in group B. Objective tests and
      subjective evaluations were performed to compare the outcomes of mini-incision
      approach with the conventional approach. Postoperative complications after the
      two approaches were also compared. RESULTS: At the 12-months follow-up, all
      patients in both groups got recovery. We found no significant differences between
      the two groups in postoperative pinch strength, grip strength, 2-point
      discrimination (2-PD), visual analogue scale (VAS) score, Levine score and the
      Disabilities of the Arm, Shoulder and Hand (DASH) score (P > 0.05). However, at
      the one-month follow-up, the percentage of patients with wound pain in group A
      was significantly lower than that in group B (0.05% vs. 0.23%, P = 0.03). At the
      12 months follow-up, the number of patients with persistent wound pain and pillar
      pain in group B were 2 (4.7%) and 3 (7.0%) respectively, while no patients showed
      wound pain and pillar pain in group A. CONCLUSION: Patients with mini-incision
      approach have satisfactory surgical outcomes, low postoperative complications,
      and good appearance.

PMID- 29471153
TI  - The prevalence and clinical significance of postgastrectomy anemia in patients
      with early-stage gastric cancer: A retrospective cohort study.
AB  - BACKGROUND: This study explored the cumulative incidence of anemia after
      gastrectomy in patients with early-stage gastric cancer and evaluated the
      relationship between postgastrectomy anemia and nutritional factors during long
      term follow-up. METHODS: The medical records of patients with stage I gastric
      cancer who underwent curative gastrectomy between January 2006 and December 2013
      were reviewed retrospectively. Hematologic parameters like hemoglobin, iron,
      ferritin, and vitamin B12 level were obtained prior to and after surgery with
      other nutritional parameters such as total protein, albumin, total cholesterol,
      triglyceride, calcium, and phosphate. Postoperative follow-up was conducted at 6
      months after surgery and then annually for 5 years. RESULTS: Among 566 patients
      who did not have anemia preoperatively, 240 (42.4%) experienced anemia at least
      once during the 5 years after gastrectomy. These 240 patients (the anemia group)
      showed lower preoperative levels of hemoglobin, iron, ferritin, and triglyceride
      than those of the patients who did not experience anemia (the normal group).
      Total gastrectomy, advanced T stage, and lymph node metastasis were significantly
      more common in the anemia group compared with the normal group. During long-term
      follow-up, the anemia group showed significantly lower serum levels of
      nutritional markers, especially triglycerides, compared with the normal group.
      The overall survival rate was significantly lower in the anemia group than in the
      normal group. CONCLUSIONS: Anemia was common among gastric cancer patients after
      gastrectomy. Total gastrectomy and advanced T stage were identified as
      independent risk factors for postgastrectomy anemia. In addition, anemia might be
      associated with nutritional problems and a poor prognosis. Thus, regular
      monitoring and appropriate management of postgastrectomy anemia are important for
      early-stage gastric cancer patients with a long life expectancy.

PMID- 29471154
TI  - Tibial component sizing and alignment of TKR components does not significantly
      affect patient reported outcome measures at six months. A case series of 474
      participants.
AB  - OBJECTIVES: Total knee replacement (TKR) is an effective means of alleviating the
      symptoms of end stage osteoarthritis. However, 20% of patients report
      dissatisfaction one year post-operatively. Previous literature has demonstrated
      contradictory evidence regarding the relationship between alignment and tibial
      component sizing with patient reported outcome measures (PROMs). We aim to
      investigate the association between alignment of TKR components and effect of
      tibial component sizing on PROMs. METHOD: A prospective, multicentre case series
      was performed at six centres. Baseline characteristics were collected at
      recruitment. Coronal and sagittal plain films were taken day one post
      operatively. Trained medical professionals blinded to outcome measured the
      alignment and degree of over/underhang of the tibial component in the coronal and
      sagittal place, with Oxford Knee Score (OKS) measured six months post
      operatively. RESULTS: 474 patients were recruited. Malaligned TKRs caused no
      significant difference in mean OKS change at six months (independent t-test) (p >
      0.05). A multivariate regression model taking into account age, gender, body mass
      index and baseline OKS also demonstrated no significant difference (p > 0.05).
      With regards to tibial component sizing, 125 (27%) of patients had appropriately
      sized tibial components, 120 (26%) had overhang and 219 (53%) had underhang with
      no significant difference in OKS between the groups (p > 0.05). CONCLUSION:
      Tibial component sizing and alignment does not significantly affect short-term
      function, as measured by OKS, after total knee replacement. Dissatisfaction after
      TKR is likely due to other factors other than alignment of implant.

PMID- 29471155
TI  - Early results of magnetic sphincter augmentation versus fundoplication for
      gastroesophageal reflux disease: Systematic review and meta-analysis.
AB  - BACKGROUND: Laparoscopic Nissen and Toupet fundoplication (LF) are currently
      considered gold-standard surgical treatment for Gastroesophageal Reflux Disease
      (GERD). Magnetic Sphincter Augmentation (MSA) is an innovative surgical procedure
      that has been showed to be effective to control GERD symptoms and to reduce
      esophageal acid exposure. The aim of this systematic review and meta-analysis was
      to compare early outcomes of LF and MSA. MATERIALS AND METHODS: PubMed, MEDLINE,
      Embase, and Cochrane databases were consulted matching the terms
      "Gastroesophageal reflux or heartburn", "LINX or magnetic sphincter augmentation"
      and "fundoplication". Pooled effect measures were calculated using an inverse
      variance weighted or Mantel-Haenszel in random effects meta-analysis.
      Heterogeneity was evaluated using I2-index and Cochrane Q-test. Meta-regression
      was used to address the effect of potential confounders. RESULTS: Seven
      observational cohort studies, published between 2014 and 2017, matched the
      inclusion criteria. Overall, 1211 patients, 686 MSA and 525 LF, were included.
      Postoperative morbidity ranged from 0 to 3% in the MSA group and from 0 to 7% in
      the LF group, and there was no mortality. Dysphagia requiring endoscopic
      dilatation occurred in 9.3% and 6.6% of patients respectively (OR = 1.56, 95% CI
      = 0.61-3.95, p = 0.119). The pooled OR of gas/bloat symptoms, ability to vomit,
      and ability to belch were 0.39 (95% CI 0.25-0.61; p < 0.001), 10.10 (95% CI 5.33
      19.15; p < 0.001), and 5.53 (95% CI 3.73-8.19; p < 0.001), respectively. The
      postoperative GERD-HRQL was similar (p = 0.101). The pooled OR of PPI suspension,
      endoscopic dilation, and reoperation were similar in the two patients groups (p =
      0.548, p = 0.119, p = 0.183, respectively). CONCLUSION: Both anti-reflux
      procedures are safe and effective up to 1-year follow-up. PPI suspension rate,
      dysphagia requiring endoscopic dilatation, and disease-related quality of life
      are similar in the two patient groups. MSA is associated with less gas/bloat
      symptoms and increased ability to vomit and belch.

PMID- 29471156
TI  - Sliding hip screw versus cannulated cancellous screws for fixation of femoral
      neck fracture in adults: A systematic review.
AB  - OBJECTIVE: Femoral neck fracture is considered a difficult fracture to treat and
      often gives rise to unsatisfactory treatment results. Cannulated cancellous
      screws (CCS) or a sliding hip screw (SHS) are the mainstream internal fixations
      used for osteosynthesis of femoral neck fractures. There is a need to integrate
      existing data through a meta-analysis to investigate the safety and effectiveness
      of CCS and SHS in the treatment of femoral neck fractures. METHOD: According to
      the Cochrane Handbook for Systematic Reviews of Interventions, we screened for
      the relevant studies by searching Google Scholar, the Cochrane Controlled Trials
      Register, the Cochrane Library, Web of Science, EMBASE, and PubMed. The PICOS
      criteria was used to make sure the included studies fulfilled the inclusion
      criteria. RESULTS: Pooled data showed that there were no significant differences
      between the SHS and CCS groups for the Harris Hip Score. Significant differences
      were found between the SHS and CCS groups in terms of union time, postoperative
      complications, blood loss, operation time, incision length and length of hospital
      stay. CONCLUSIONS: Although the SHS and CCS groups showed similar functional
      recovery in treatment of femoral neck fracture in terms of the Harris Hip Score,
      the SHS group showed fewer postoperative complications and faster union time for
      patients with femoral neck fractures. Therefore, compared with CCS, the use of
      SHS may be a more effective treatment of femoral neck fractures.

PMID- 29471157
TI  - The effectiveness and safety of aminocaproic acid for reducing blood loss in
      total knee and hip arthroplasty: A meta-analysis.
AB  - OBJECTIVE: This meta-analysis aimed to evaluate the safety and efficacy of
      aminocaproic acid in total knee arthroplasty (TKA) and total hip arthroplasty
      (THA). METHODS: The electronic databases include PubMed, Medline, Embase, Web of
      Science and the Cochrane Library from inception to January, 2018. Two reviewers
      abstracted total blood loss, hemoglobin drop, transfusion requirements, and
      postoperative complications. Data were using fixed-effects or random-effects
      models with weighted mean differences and risk difference for continuous and
      dichotomous variables, respectively. STATA 14.0 was used to perform the meta
      analysis. RESULTS: Six studies encompassing 756 participants were retrieved for
      this meta-analysis. Our study indicated that intravenous aminocaproic acid was
      associated with a significantly reduction in total blood loss, hemoglobin drop
      and need for transfusion. Additionally, no increased risk of thromboembolic
      events were identified. CONCLUSION: Based on the present meta-analysis,
      intravenous aminocaproic acid is effective and safe in total knee and hip
      arthroplasty without increasing the incidence of thromboembolic events. Further
      studies should focus on the comparison of aminocaproic acid and TXA in
      arthroplasties.

PMID- 29471158
TI  - Road traffic injuries: Cross-sectional cluster randomized countrywide population
      data from 4 low-income countries.
AB  - INTRODUCTION: Road traffic injuries (RTI) are a leading cause of morbidity and
      mortality around the world. The burden is highest in low and middle-income
      countries (LMICs) and is increasing. We aimed to describe the epidemiology of
      RTIs in 4 low-income countries using nationally representative survey data.
      METHODS: The Surgeons Overseas Assessment of Surgical Needs (SOSAS) survey tool
      was administered in four countries: Sierra Leone, Rwanda, Nepal and Uganda. We
      performed nationally representative cross-sectional, cluster randomized surveys
      in each country. Information regarding demographics, injury characteristics,
      anatomic location of injury, healthcare seeking behavior, and disability from
      injury was collected. Data were reported with descriptive statistics and
      evaluated for differences between the four countries using statistical tests
      where appropriate. RESULTS: A total of 13,765 respondents from 7115 households in
      the four countries were surveyed. RTIs occurred in 2.2% (2.0-2.5%) of the
      population and accounted for 12.9% (11.5-14.2%) of all injuries incurred. The
      mean age was 34 years (standard deviation +/-1years); 74% were male. Motorcycle
      crashes accounted for 44.7% of all RTIs. The body regions most affected included
      head/face/neck (36.5%) followed by extremity fractures (32.2%). Healthcare was
      sought by 78% road injured; 14.8% underwent a major procedure (requiring
      anesthesia). Major disability resulting in limitations of work or daily activity
      occurred in 38.5% (33.0-43.9%). CONCLUSION: RTIs account for a significant
      proportion of disability from injury. Younger men are most affected, raising
      concerns for potential detrimental consequences to local economies. Prevention
      initiatives are urgently needed to stem this growing burden of disease;
      additionally, improved access to timely emergency, trauma and surgical care may
      help alleviate the burden due to RTI in LMICs.

PMID- 29471159
TI  - Operation versus watchful waiting in asymptomatic or minimally symptomatic
      inguinal hernias: The meta-analysis results of randomized controlled trials.
AB  - INTRODUCTION: The aim of this article was to compare and analyze the outcomes of
      surgical repair and watchful waiting (WW) in the treatment of asymptomatic or
      minimally symptomatic inguinal hernias. METHODS: A systematic literature review
      was undertaken to identify studies that compare surgical repair and watchful
      waiting in asymptomatic or minimally symptomatic inguinal hernias. And all
      related data matching our standards were abstracted for Meta-analysis with RevMan
      5.0.1. RESULTS: Less pain was observed in Operation group. However, there were no
      significant differences in Physical Component Score (PCS), mortality, surgical
      complications and postoperative hernia recurrence between WW group and Operation
      group. But a great number of patients would develop significant hernia-related
      symptoms and cross over to surgery over time in WW group. CONCLUSIONS: Patients
      have relative less pain in operation group compared with WW group. Although WW is
      safe in patients with asymptomatic or minimally symptomatic inguinal hernias,
      however, this strategy would merely delay rather than avoid surgical repair of
      hernias in the majority of inguinal hernia patients.

PMID- 29471160
TI  - Persistent first intersegmental artery (PFIA) visualized by three-dimensional
      computed tomography angiography in Chinese population.
AB  - BACKGROUND: Persistent first intersegmental artery (PFIA) is one of the most
      frequently vertebral artery (VA) variations. The presence of PFIA obviously
      increases the complexity and difficulty of vertebral lesion treatment. Thus,
      preoperative detection of PFIA is necessary to increase the successful rate of
      surgeries. We attempted to evaluate the utility value of three-dimension (3D)
      computed tomography angiography (CTA) for detecting PFIA in the north Chinese
      population. MATERIALS AND METHODS: Consecutive patients subjected to CTA between
      June 2012 and March 2014 were recruited from 5 clinical centers in the north of
      China. . The VA-cervical atlas complexus were observed by CTA. The assessment of
      PFIA was performed by reconstructing the images via Materialise's interactive
      medical image control system (MIMICS) and the measurement of VA diameter was
      performed on the source images. PFIA including unilateral and bilateral was
      calculated. The dominant side was defined as the unilateral VA with 130% fold
      larger diameter than the other side. RESULTS: A total of 200 north Chinese
      patients with mean age of 57.8 +/- 9.3 years old were enrolled in the present
      study. Total 400 VA-cervical atlas complexus were observed by 3D-CTA, among which
      9 complexus (2.25%) were diagnosed with PFIA, and 3 complexus (0.75%) were
      presented with the dominant VA. The spinal surgical procedures were performed
      successfully in all the patients with no injury and complications to the VA.
      CONCLUSIONS: The incidence of PFIA in 400 VA-cervical atlas complexus are
      relatively high (2.25%) in our patient population. On the basis of relatively
      high prevalence of this anomaly, the preoperative detection of PFIA by 3D-CTA is
      recommended for the north Chinese population.

PMID- 29471161
TI  - Peripheral artery disease and antiplatelet treatment.
AB  - Peripheral artery disease (PAD) is one of the most important causes of
      cardiovascular morbidity and mortality and its prevalence is alarmingly
      increasing in modern societies. PAD shares common characteristics with the other
      atherosclerotic diseases but involves specifically the arteries of the lower
      extremities. Apart from the changes in lifestyle, antiplatelet agents are the
      hallmark of the treatment and improve the symptoms as well as the progression of
      the disease. Aspirin is the cornerstone of treatment and is administrated in
      doses ranging from 75 to 325mg daily. Additionally, cilostazol and clopidogrel
      have an important therapeutic role too. Novel antiplatelet agents are the subject
      of research in both experimental and clinical studies in order to evaluate the
      efficacy and safety profile. The most important antiplatelet factors which are
      under investigation are the novel P2Y12 receptor inhibitors prasugrel and
      ticagrelor. Furthermore, vorapaxar, a protease-activated receptor inhibitor,
      exhibits antiplatelet properties and has been studied in PAD.

PMID- 29471163
TI  - Capacity and recycling of polyoxometalate applied in As(III) oxidation by Fe(II)
      Amended zero-valent aluminum.
AB  - Arsenic remediation is often initiated by oxidizing As(III) to As(V) to alleviate
      its toxicity and mobility. Due to the easy availability, zero-valent Al (ZVAl)
      like Al can was considered as potential alternatives to facilitate As(III)
      oxidation. This study determined the capability and recycling of polyoxometalate
      (POM) to catalyze As(III) oxidation in Fe(II)-amended ZVAl systems. POM acquired
      electrons from ZVAl more effectively at pH 1 than at pH 2. While 76% of the
      reduced POM [POM(e-)] reacted with O2(g) to generate H2O2 at pH 1, only 60% of
      POM(e-) was used to produce H2O2 at pH 2. The remaining POM(e-) was oxidized by
      the generated H2O2. Such additional consumption of POM(e-) and H2O2 led to the
      incomplete As(III) oxidation in the system without residual ZVAl and emphasized
      the need for a continuous electron supply from ZVAl to compensate the depletion
      of POM(e-). After the hydrolyzation at pH 6.0, the XANES data evidenced that not
      only As(V) but WO4 released from the POM retained on surfaces of Al/Fe
      hydroxides. The competition for sorption sites on Al/Fe hydroxides between As(V)
      and WO4 led to the incomplete As removal. Despite the loss of WO4, the POM re
      polymerized at pH 1 still showed the comparable capability to catalyze As(III)
      oxidation with original POM. This study revealed electron transfer pathways from
      ZVAl to As(III) as catalyzed by POM and evidenced the effective POM recycling
      after As removal, which lowers the cost of POM application and turns the
      ZVAl/Fe(II)/POM/O2 system into a practical strategy for As remediation.

PMID- 29471164
TI  - Nanoparticles of volcanic ash as a carrier for toxic elements on the global
      scale.
AB  - At present, there is concern about engineered nanoparticles in the environment,
      whereas natural nanoparticles (NPs) and their impact are often neglected. In our
      paper, we demonstrate the important role of nanoparticles of volcanic ash in
      transport of toxic elements on a global scale. A single volcanic eruption can
      eject millions of tons of ash. NPs of volcanic ash reach the upper troposphere
      and the stratosphere and may "travel" around the world for years affecting human
      health, environment, and even climate. So far, there is a gap in exposure
      assessment of volcanic ash NPs since their chemical composition remains largely
      unknown. Here we show for the first time that volcanic ash NPs can serve as an
      important carrier for potentially toxic elements. The concentrations of Ni, Zn,
      Cd, Ag, Sn, Se, Te, Hg, Tl, Pb, Bi in volcanic ash NPs (<100 nm) were found to be
      10-500 times higher than total contents of these elements in bulk samples. This
      is valid for volcanoes from different regions of the world (Kamchatka, Far East
      of Russia and Andes, Chile). The work opens a new door into studies on
      biogeochemical impact of volcanic ash.

PMID- 29471162
TI  - Hydrogen peroxide production by lactobacilli promotes epithelial restitution
      during colitis.
AB  - Inflammatory bowel disease (IBD) is a multifactorial chronic inflammatory disease
      of the gastrointestinal tract, characterized by cycles of acute flares, recovery
      and remission phases. Treatments for accelerating tissue restitution and
      prolonging remission are scarce, but altering the microbiota composition to
      promote intestinal homeostasis is considered a safe, economic and promising
      approach. Although probiotic bacteria have not yet fulfilled fully their promise
      in clinical trials, understanding the mechanism of how they exert beneficial
      effects will permit devising improved therapeutic strategies. Here we probe if
      one of the defining features of lactobacilli, the ability to generate nanomolar
      H2O2, contributes to their beneficial role in colitis. H2O2 generation by wild
      type L. johnsonii was modified by either deleting or overexpressing the enzymatic
      H2O2 source(s) followed by orally administering the bacteria before and during
      DSS colitis. Boosting luminal H2O2 concentrations within a physiological range
      accelerated recovery from colitis, while significantly exceeding this H2O2 level
      triggered bacteraemia. This study supports a role for increasing H2O2 within the
      physiological range at the epithelial barrier, independently of the enzymatic
      source and/or delivery mechanism, for inducing recovery and remission in IBD.

PMID- 29471165
TI  - Emission characteristics of PCDD/Fs in stack gas from municipal solid waste
      incineration plants in Northern China.
AB  - Emission characteristics including congener's profile, gas emissions and toxic
      equivalent concentration (TEQ) indicators of polychlorinated dibenzo-p-dioxins
      and dibenzofurans (PCDD/Fs) in 57 stack gas samples from 6 municipal solid waste
      incinerators (MSWIs) in Northern China were investigated by gas chromatography
      high resolution mass spectrometry (HRGC-HRMS). Additionally, PCDD/Fs formation
      mechanisms from the MSWIs were briefly discussed. Results revealed that the
      concentrations and equivalent concentrations of PCDD/Fs emissions in stack gas
      from 6 MSWIs were in the range of 0.11-2.53 ng Nm-3 and 0.007-0.059 ng TEQ Nm-3,
      respectively. The emission factors of PCDD/Fs from 6 MSWIs varied from 0.027 to
      0.225 MUg I-TEQ tonne-1, with a mean value of 0.17 MUg I-TEQ tonne-1 waste, which
      was estimated to an annual emission of 234.96 mg I-TEQ of PCDD/Fs from 6 MSWIs to
      the atmosphere. O8CDD, O8CDF and 1,2,3,4,6,7,8-H7CDD were the indicatory
      compounds of PCDD/Fs to apportion the sources of PCDD/Fs in environmental medium
      especially in ambient environment of MSWIs. 1,2,3,7,8,9-H6CDF and 1,2,3,4,7,8
      H6CDF can be used as TEQ indicators for monitoring PCDD/Fs emission. Based on the
      positive matrix factorization (PMF) model, eight factors were extracted by the
      PMF analysis. Formation of low-chlorinated PCDDs (1,2,3,7,8-P5CDD, 1,2,3,4,7,8
      H6CDD, 1,2,3,6,7,8-H6CDD and 1,2,3,7,8,9-H6CDD) possessed strong correlation, and
      the chlorophenols maybe the important precursors of low-chlorinated PCDDs, which
      were generated within the low chlorinated content. Penta- and hexa-PCDFs
      formation in stack gas from MSWI may block catalytic sites for PCDFs formation
      from carbon. Meanwhile, possible formation mechanisms of high-chlorinated PCDDs
      (hepta- and octa-PCDDs) and high-chlorinated PCDFs (hepta- and octa-PCDFs) were
      respectively dependent.

PMID- 29471166
TI  - Neurobehavioral effects of two metabolites of BDE-47 (6-OH-BDE-47 and 6-MeO-BDE
      47) on zebrafish larvae.
AB  - Two metabolites, OH-BDEs and MeO-BDEs, of polybrominated diphenyl ethers (PBDEs)
      were ubiquitously detected in animal tissues and environmental samples, drawing a
      widely public concern to their toxicity. The comparison of toxicity between PBDEs
      and their metabolites has been a focus in recent years, however, comparisons
      seldom involve neurobehavioral toxicity of PBDEs metabolites in published works.
      In this study, zebrafish larvae were exposed to 6-OH-BDE-47 and 6-MeO-BDE-47 and
      their neurobehavioral traits (including locomotion, path angle, and social
      activity) were recorded using the instrument Zebrabox; meanwhile, light
      illumination was used as stimuli in the test duration. The results showed larvae
      were more active in dark periods than light periods, and preferred turning right
      (+) to left (-). Effects of the two metabolites varied in different behavioral
      indicators. They induced different effects on path angle but did not reverse the
      left-right asymmetry. 6-OH-BDE-47 did not induce the effects on larval locomotion
      and social activity, but mainly decreased average and routine turn numbers; 6-MeO
      BDE-47 promoted larvae responsive turns but inhibited social activity. This study
      offered new experimental means to the neurobehavioral toxicity of various PBDE
      metabolites. Further studies may focus on the toxic mechanisms of specific
      neurobehavioral traits.

PMID- 29471167
TI  - Adsorption of pharmaceuticals onto isolated polyamide active layer of NF/RO
      membranes.
AB  - Adsorption of trace organic compounds (TrOCs) onto the membrane materials has a
      great impact on their rejection by nanofiltration (NF) and reverse osmosis (RO)
      membranes. This study aimed to investigate the difference in adsorption of
      various pharmaceuticals (PhACs) onto different NF/RO membranes and to demonstrate
      the necessity of isolating the polyamide (PA) active layer from the polysulfone
      (PS) support layer for adsorption characterization and quantification. Both the
      isolated PA layers and the PA+PS layers of NF90 and ESPA1 membranes were used to
      conduct static adsorption tests. Results showed that apparent differences existed
      between the PA layer and the PA+PS layer in the adsorption capacity of PhACs as
      well as the time necessary to reach the adsorption equilibrium. PhACs with
      different physicochemical properties could be adsorbed to different extents by
      the isolated PA layer, which was mainly attributed to electrostatic
      attraction/repulsion and hydrophobic interactions. The PA layer of ESPA1
      exhibited apparently higher adsorption capacities for the positively charged
      PhACs and similar adsorption capacities for the neutral PhACs although it had
      significantly less total interfacial area (per unit membrane surface area) for
      adsorption compared to the PA layer of NF90. The higher affinity of the PA layer
      of ESPA1 for the PhACs could be due to its higher capacity of forming hydrogen
      bonds with PhACs resulted from the modified chemistry with more -OH groups. This
      study provides a novel approach to determining the TrOC adsorption onto the
      active layer of membranes for the ease of investigating adsorption mechanisms.

PMID- 29471168
TI  - Developmental toxicity of penconazole in Zebrfish (Danio rerio) embryos.
AB  - Penconazole is a widely used fungicide that is toxic to a variety of organisms
      including fish. In the present study, we investigated the developmental toxicity
      of penconazole on zebrafish embryos by exposing to different concentrations of
      penconazole (0.8, 1.6 and 2.4 mg/L) from 4-h post-fertilization (hpf). Hatching,
      survival, and heart rates, body length, malformation and expression of several
      genes were detected. The results showed that penconazole exposure induced
      developmental toxicity, including delayed hatching, reduced survival, and heart
      rate. In addition to this, exposure to penconazole caused malformations,
      including pericardial edema, yolk sac edema, axial malformation, tail
      malformation and spinal curvature. Furthermore, RT-PCR results showed that mRNA
      levels of antioxidant genes were down-regulated after penconazole exposure. On
      the other hand, mRNA levels of interleukin 1 beta and interferon in embryos were
      up-regulated after exposure to penconazole. In summary, our data indicated that
      penconazole cause embryonic development toxicity on zebrafish embryos.

PMID- 29471169
TI  - PEGylated dendritic polyglycerol conjugate targeting NCAM-expressing
      neuroblastoma: Limitations and challenges.
AB  - Neural cell adhesion molecule (NCAM) is found to be a stem-cell marker in several
      tumor types and its overexpression is known to correlate with increased
      metastatic capacity. To combine extravasation- and ligand-dependent targeting to
      NCAM overexpressing-cells in the tumor microenvironment, we developed a PEGylated
      NCAM-targeted dendritic polyglycerol (PG) conjugate. Here, we describe the
      synthesis, physico-chemical characterization and biological evaluation of a PG
      conjugate bearing the mitotic inhibitor paclitaxel (PTX) and an NCAM-targeting
      peptide (NTP). PG-NTP-PTX-PEG was evaluated for its ability to inhibit
      neuroblastoma progression in vitro and in vivo as compared to non-targeted
      derivatives and free drug. NCAM-targeted conjugate inhibited the migration of
      proliferating endothelial cells, suggesting it would be able to inhibit tumor
      angiogenesis. The targeting conjugate provided an improved binding and uptake on
      IMR-32 cells compared to non-targeted control. However, these results did not
      translate to our in vivo model on orthotopic neuroblastoma bearing mice.

PMID- 29471170
TI  - Chitosan whisker grafted with oligo(lactic acid) nanoparticles via a green
      synthesis pathway and Lidocaine encapsulation: is there any forgotten issue?

PMID- 29471171
TI  - Triggering the activation of Activin A type II receptor in human adipose stem
      cells towards tenogenic commitment using mechanomagnetic stimulation.
AB  - Stem cell therapies hold potential to stimulate tendon regeneration and
      homeostasis, which is maintained in response to the native mechanical
      environment. Activins are members of the mechano-responsive TGF-beta superfamily
      that participates in the regulation of several downstream biological processes.
      Mechanosensitive membrane receptors such as activin can be activated in different
      types of stem cells via magnetic nanoparticles (MNPs) through remote magnetic
      actuation resulting in cell differentiation. In this work, we target the Activin
      receptor type IIA (ActRIIA) in human adipose stem cells (hASCs), using anti
      ActRIIA functionalized MNPs, externally activated through a oscillating magnetic
      bioreactor. Upon activation, the phosphorylation of Smad2/3 is induced allowing
      translocation of the complex to the nucleus, regulating tenogenic transcriptional
      responses. Our study demonstrates the potential remote activation of MNPs tagged
      hASCs to trigger the Activin receptor leading to tenogenic differentiation. These
      results may provide insights toward tendon regeneration therapies.

PMID- 29471172
TI  - Enhancing glioblastoma treatment using cisplatin-gold-nanoparticle conjugates and
      targeted delivery with magnetic resonance-guided focused ultrasound.
AB  - Glioblastoma (GBM) is the most common and aggressive primary brain tumor
      resulting in high rates of morbidity and mortality. A strategy to increase the
      efficacy of available drugs and enhance the delivery of chemotherapeutics through
      the blood brain barrier (BBB) is desperately needed. We investigated the
      potential of Cisplatin conjugated gold nanoparticle (GNP-UP-Cis) in combination
      with MR-guided Focused Ultrasound (MRgFUS) to intensify GBM treatment. Viability
      assays demonstrated that GNP-UP-Cis greatly inhibits the growth of GBM cells
      compared to free cisplatin and shows marked synergy with radiation therapy.
      Additionally, increased DNA damage through gammaH2AX phosphorylation was observed
      in GNP-UP-Cis treated cells, along with enhanced platinum concentrations. In
      vivo, GNP-UP-Cis greatly reduced the growth of GBM tumors and MRgFUS led to
      increased BBB permeability and GNP-drug delivery in brain tissue. Our studies
      suggest that GNP-Cis conjugates and MRgFUS can be used to focally enhance the
      delivery of targeted chemotherapeutics to brain tumors.

PMID- 29471173
TI  - Correlating growth mechanism and morphology in Cu-TCNQ organometallic complex: A
      microscopic study.
AB  - The structure-property correlation in the Cu-TCNQ organometallic complex is very
      important for explaining its unusual electrical, optical and magnetic properties.
      Consequently several morphological studies and their correlation with the
      properties of these materials can be found in the literature, although no
      systematic study of various morphologies with growth conditions and their
      correlation has been reported to the best of our knowledge. Therefore in this
      manuscript the interconversion of various morphologies is reported using electron
      and probe microscopies. A conventional Cu TEM grid acted as the copper source to
      form a Cu-TCNQ complex and the complex, which formed at the surface of the TEM
      grid. The complex thus prepared was characterized by FTIR and Raman spectroscopic
      techniques. The shifting of -CN from 2221 cm-1 (TCNQ) to 2201 cm-1 indicates
      formation of a complex and the identical nature of IR spectra in two phases
      indicates that they are polymorphs. The morphologies of Cu-TCNQ were followed
      through FE-SEM and TEM studies. Various morphologies such as needle, square tube,
      platelet etc. were observed as a function of time. A distinct transition from
      needle to platelet morphology was observed as the complex grew. The conductance
      of various morphologies in phase-I as well as phase-II were also measured and
      compared by Spreading Resistance Imaging (SRI) at different bias voltage i.e. 1
      V, 3 V and 5 V.

PMID- 29471174
TI  - Characterizing gestational weight gain in a cohort of Indigenous Australian
      women.
AB  - OBJECTIVE: to determine the adequacy of gestational weight gain for a cohort of
      Indigenous Australian women and investigate whether it is associated with pre
      pregnancy body mass index. DESIGN: analysis of observational data collected from
      a longitudinal cohort study that follows Indigenous Australian women through
      pregnancy. SETTING: women recruited through antenatal clinics in regional and
      remote towns in NSW, Australia to the Gomeroi gaaynggal program. PARTICIPANTS:
      110 pregnant women who either identified as being an Indigenous Australian or as
      carrying an Indigenous child. MEASUREMENTS AND FINDINGS: measurements included
      weight and height, self-reported pre-pregnancy weight and smoking status, parity
      and health conditions that may contribute to gestational weight gain, such as
      hypertensive or diabetic disorders. Compared to the 2009 Institute of Medicine
      recommendations for gestational weight gain and based on prepregnancy body mass
      index, the rate of adequate gestational weight gain in this cohort was very low
      (15%). 32% of women had inadequate weight gain and 54% had excessive weight gain.
      The highest rate of excessive gestational weight gain was found in overweight
      women (74%), with rates of 48% and 50% found in healthy and obese (all classes)
      categories, respectively. Parity (coefficient 4.5, p<0.01) and hypertension
      (coefficient 4.8, p = 0.04) were found to be significantly associated with
      gestational weight gain in mixed model linear regression. CONCLUSIONS: few women
      gained adequate gestational weight gain in this study. Culturally acceptable ways
      of addressing this issue are needed for this group of women, as inadequate and
      excessive rates of gestational weight gain have health implications for women and
      their offspring. IMPLICATIONS FOR PRACTICE: a systematic approach to addressing
      gestational weight gain within antenatal care is required, including asking about
      diet and exercise, for all women identifying as Indigenous Australian.

PMID- 29471175
TI  - Midwifery education in the U.S. - Certified Nurse-Midwife, Certified Midwife and
      Certified Professional Midwife.
AB  - US midwifery education is provided through graduate education for the CNM/CM and
      didactic education with apprenticeship for the CPM. Clinical practice varies
      throughout the country depending on the credential held and current state
      legislation. A lack of clinical sites for midwifery education is a significant
      challenge to all programs and a barrier to meeting the national maternity care
      provider shortage.

PMID- 29471177
TI  - Needs of students seeking careers in communication sciences and disorders and
      barriers to their success.
AB  - PURPOSE: The purpose of this study was to identify the needs for and barriers to
      success of underrepresented students in the Communication Sciences and Disorders
      field and to determine factors linked to student persistence and academic
      achievement. METHOD: An online survey was completed by 126 undergraduates
      pursuing graduate studies in Communication Sciences and Disorders. Data were
      subjected to Mann-Whitney U and Kruskal-Wallis H tests. RESULTS: Survey responses
      indicated that financial matters exerted the most influence on students'
      preparation for and number of choices for graduate-school applications. However,
      socioeconomic status was associated with needed financial support for paying
      tuition and completing the admission process. In addition, students at lower
      socioeconomic status reported spending fewer hours studying for tests and earned
      lower grade-point averages than peers who self-identified with a relatively high
      socioeconomic status. The findings also show a relationship between students'
      grade-point averages and family members' levels of education. The majority
      reported that mothers had earned the highest degree in their household, followed
      by siblings, themselves, and fathers. CONCLUSIONS: The findings suggest that
      students of low socioeconomic status were less academically prepared than those
      self-reporting a higher status. Moreover, the presence of a role model, such as a
      college-educated family member, may affect academic performance. Therefore,
      interventions for students at risk of not gaining admissions to graduate school
      include financial assistance and mentoring and advising programs.

PMID- 29471176
TI  - Rhythmic performance in hypokinetic dysarthria: Relationship between reading,
      spontaneous speech and diadochokinetic tasks.

PMID- 29471178
TI  - A role for epistemic trust in speech-language pathology: A tutorial paper.
AB  - This paper provides an introduction to epistemic trust for speech-language
      pathologists (SLPs). 'Epistemic trust' describes a specific form of trust that an
      individual places in others when learning about the world, particularly the
      social world. To date, the relevance of epistemic trust to SLP clinical practice
      has received little theoretical or empirical attention. The aim of this paper is
      to define epistemic trust and explain its relationship with parent-child
      attachment and mentalization which have, in turn, been linked with language
      development and use. Suggestions are made for ways in which SLPs may encourage
      epistemic trust in clients, emphasizing the need to establish strong therapeutic
      alliances. The authors conclude that epistemic trust is an important
      consideration for SLPs and that further research exploring the relationship
      between epistemic trust and language skills is needed to better understand the
      interplay of these variables and inform clinical practice.

PMID- 29471179
TI  - The link between income inequality and health in Europe, adding strength
      dimensions of primary care to the equation.
AB  - Income inequality has been clearly associated with reduced population health. A
      body of evidence suggests that a strong primary care system may mitigate this
      negative association. The aim of this study is to assess the strength of the
      primary care system's effect on the inverse association between income inequality
      and health in Europe. Health is operationalised using four cross-sectional
      outcomes: self-rated health, life expectancy, mental well-being, and infant
      mortality. Strength of the primary care system is measured using the framework of
      the Primary Health Care Activity Monitor Europe, and income inequality by the
      Gini coefficient. Multiple regression models with interaction terms were used.
      The results confirm that especially the structure and continuity dimension of
      primary care strength can buffer the inverse association between income
      inequality and health. European policymakers should therefore focus on
      strengthening primary care systems in order to reduce inequity in health.

PMID- 29471180
TI  - Linking financial hardship throughout the life-course with psychological distress
      in old age: Sensitive period, accumulation of risks, and chain of risks
      hypotheses.
AB  - The primary objective was to investigate the life course hypotheses - sensitive
      period, chain of risks, and accumulation of risks - in relation to financial
      hardship and psychological distress in old age. We used two Swedish longitudinal
      surveys based on nationally representative samples. The first survey includes
      people 18-75 years old with multiple waves, the second survey is a longitudinal
      continuation, including people 76 + years old. The analytical sample included
      2990 people at baseline. Financial hardship was assessed in childhood
      (retrospectively), at the mean ages of 54, 61, 70, and 81 years. Psychological
      distress (self-reported anxiety and depressive symptoms) was assessed at the same
      ages. Path analysis with WLSMV estimation was used. There was a direct path from
      financial hardship in childhood to psychological distress at age 70 (0.26, p =
      0.002). Financial hardship in childhood was associated with increased risk of
      psychological distress and financial hardship both at baseline (age 54), and
      later. Financial hardship, beyond childhood, was not independently associated
      with psychological distress at age 81. Higher levels of education and employment
      decreased the negative effects of financial hardship in childhood on the risk of
      psychological distress and financial hardship later on. There was a bi
      directional relationship between psychological distress and financial hardship;
      support for health selection was slightly higher than for social causation. We
      found that psychological distress in old age was affected by financial hardship
      in childhood through a chain of risks that included psychological distress
      earlier in life. In addition, financial hardship in childhood seemed to directly
      affect psychological distress in old age, independent of other measured
      circumstances (i.e., chains of risks). Education and employment could decrease
      the effect of an adverse financial situation in childhood on later-life
      psychological distress. We did not find support for accumulation of risks when
      including tests of all hypotheses in the same model.

PMID- 29471181
TI  - Clinic access and teenage birth rates: Racial/ethnic and spatial disparities in
      Houston, TX.
AB  - Teenage motherhood is a pressing issue in the United States, and one that is
      disproportionately affecting racial/ethnic minorities. In this research, we
      examine the relationship between the distance to the nearest reproductive health
      clinic and teenage birth rates across all zip codes in Houston, Texas. Our
      primary data come from the Texas Department of State Health Services. We use
      spatial regression analysis techniques to examine the link between clinic
      proximity and local teenage birth rates for all females aged 15 to 19, and
      separately by maternal race/ethnicity. We find, overall, limited support for a
      connection between clinic distance and local teenage birth rates. However,
      clinics seem to matter most for explaining non-Hispanic white teenage birth
      rates, particularly in high-poverty zip codes. The racial/ethnic and economic
      variation in the importance of clinic distance suggests tailoring clinic outreach
      to more effectively serve a wider range of teenage populations. We argue social
      accessibility should be considered in addition to geographic accessibility in
      order for clinics to help prevent teenage pregnancy.

PMID- 29471182
TI  - The impact of vitamin A supplementation in childhood on adult outcomes: An
      exploration of mechanisms, timing of exposure, and heterogeneous effects.
AB  - There is now a critical threshold of evidence documenting the relationship
      between one's exposure to shocks in early life and outcomes in adulthood. Using
      Nepal's vitamin A supplementation program, this study provides additional
      insights on the mechanisms and differences in effects by the timing of the first
      exposure and across different groups. The program's sequential rollout between
      1993 and 2001 and the age eligibility provide an exogenous variation in exposure
      to the program. I utilize that variation and data on more than 700,000
      individuals from the 2011 census to estimate the program's causal effect on long
      term health and educational outcomes. I find that the program reduced the
      probability of having a disability but had no effect on educational outcomes. The
      positive effects on disability seem to have improved marriage prospects. The
      program also had different effects on individuals based on their timing of the
      exposure to the program, with an early exposure strengthening the positive health
      effects. Effects also differed by the individual's gender and ethnicity. They
      were more pronounced for men and individuals from traditionally advantaged ethnic
      groups. The findings suggest that long-term effects can differ even when the take
      up rate is similar for different segments of the population.

PMID- 29471183
TI  - Axillary motor nerve conduction study: Description of technique and provision of
      normative data.
AB  - BACKGROUND: Axillary nerve lesions can commonly occur secondary to trauma or
      brachial plexopathy. Our aim was to describe our technique of axillary nerve
      motor conduction studies and provide the respective normal values. METHODS:
      Active electrode was positioned over the most prominent portion of the middle
      deltoid, approximately 5-7 cm distal to the acromion. Reference electrode was
      positioned over the acromion. Ground electrode was placed between the active and
      the reference electrodes. Supramaximal stimulation was at the Erb's point.
      RESULTS: A total of 154 participants (61% male, age range 18-84) were included.
      There was a significant positive correlation between the subjects' age and the
      onset latency (Spearman's rho 0.312, p < 0.001) and a significant negative
      correlation between the participants' age and the CMAP (Spearman's rho -0.481, p
      < 0.001). For the total male population the lower normal value for the CMAP was
      7.6 mV and the higher normal value for the onset latency was 5.0 ms. For the
      total female population the respective normal values were 6.5 mV and 3.5 ms. In
      order to detect an axillary nerve lesion, asymmetry of >40% in the CMAPS between
      the symptomatic and the asymptomatic side show a sensitivity of 95.2% and a
      specificity of 96.6%. CONCLUSION: We described our technique of axillary nerve
      motor conduction studies and provided the respective normal values stratified for
      age and gender. When suspecting an axillary nerve lesion it is always worth
      performing axillary motor NCS bilaterally and compare the CMAPs.

PMID- 29471184
TI  - Targeting metabotropic glutamate receptors for the treatment of
      neuroinflammation.
AB  - A large body of evidence suggests that neuroinflammation lies at the core of
      nearly all CNS disorders, including psychiatric disorders. Invading and local
      immune cells orchestrate the series of events that lead to either tissue repair
      or damage in response to neuroinflammation. Both lymphocytes and microglia
      express metabotropic glutamate (mGlu) receptors, which respond to glutamate or
      other endogenous activators (e.g. some kynurenine metabolites of tryptophan
      metabolism) influencing immune phenotype and the balance between pro-inflammatory
      and anti-inflammatory cytokines. Here, we offer an up-to-date on the role of
      individual mGlu receptor subtypes in the regulation of innate and adaptive immune
      response, highlighting the relevance of this information in the development of
      subtype-selective mGlu receptor ligands for treatment of CNS disorders.

PMID- 29471185
TI  - The Attention Training Technique improves Children's ability to delay
      gratification: A controlled comparison with progressive relaxation.
AB  - The ability to delay gratification at a young age is a predictor of
      psychological, cognitive, health, and academic later-life outcomes. This study
      aimed to extend earlier research and explore whether a metacognitive
      intervention, Wells' (1990) Attention Training Technique (ATT), could improve
      young children's ability to delay gratification compared to an active-control
      (Progressive Muscle Relaxation: PMR), and no-intervention group. One hundred and
      one children aged 5-6 years old were recruited from schools. Classes of children
      were randomly allocated to receive the ATT, PMR or no-intervention and tested at
      pre- and post-intervention on measures of delay of gratification (the Marshmallow
      Test) and verbal inhibition (Day/Night Task). Results showed that, even when
      covariates were controlled for, following ATT, children delayed gratification
      significantly longer than after PMR or no-intervention. ATT also improved verbal
      inhibition compared with the no-intervention group, whilst PMR did not. The
      results add to earlier findings; ATT appears to provide a simple and effective
      way of improving young children's ability to delay gratification which has
      previously been shown to predict positive outcomes in later-life.

PMID- 29471186
TI  - Maternal exposure to ambient PM10 during pregnancy increases the risk of
      congenital heart defects: Evidence from machine learning models.
AB  - Previous research suggested an association between maternal exposure to ambient
      air pollutants and risk of congenital heart defects (CHDs), though the effects of
      particulate matter <=10MUm in aerodynamic diameter (PM10) on CHDs are
      inconsistent. We used two machine learning models (i.e., random forest (RF) and
      gradient boosting (GB)) to investigate the non-linear effects of PM10 exposure
      during the critical time window, weeks 3-8 in pregnancy, on risk of CHDs. From
      2009 through 2012, we carried out a population-based birth cohort study on 39,053
      live-born infants in Beijing. RF and GB models were used to calculate odds ratios
      for CHDs associated with increase in PM10 exposure, adjusting for maternal and
      perinatal characteristics. Maternal exposure to PM10 was identified as the
      primary risk factor for CHDs in all machine learning models. We observed a clear
      non-linear effect of maternal exposure to PM10 on CHDs risk. Compared to 40MUgm
      3, the following odds ratios resulted: 1) 92MUgm-3 [RF: 1.16 (95% CI: 1.06,
      1.28); GB: 1.26 (95% CI: 1.17, 1.35)]; 2) 111MUgm-3 [RF: 1.04 (95% CI: 0.96,
      1.14); GB: 1.04 (95% CI: 0.99, 1.08)]; 3) 124MUgm-3 [RF: 1.01 (95% CI: 0.94,
      1.10); GB: 0.98 (95% CI: 0.93, 1.02)]; 4) 190MUgm-3 [RF: 1.29 (95% CI: 1.14,
      1.44); GB: 1.71 (95% CI: 1.04, 2.17)]. Overall, both machine models showed an
      association between maternal exposure to ambient PM10 and CHDs in Beijing,
      highlighting the need for non-linear methods to investigate dose-response
      relationships.

PMID- 29471187
TI  - Mechanistic explanation of time-dependent cross-phenomenon based on quorum
      sensing: A case study of the mixture of sulfonamide and quorum sensing inhibitor
      to bioluminescence of Aliivibrio fischeri.
AB  - Cross-phenomenon in which the concentration-response curve (CRC) for a mixture
      crosses the CRC for the reference model has been identified in many studies,
      expressed as a heterogeneous pattern of joint toxic action. However, a
      mechanistic explanation of the cross-phenomenon has thus far been extremely
      insufficient. In this study, a time-dependent cross-phenomenon was observed, in
      which the cross-concentration range between the CRC for the mixture of
      sulfamethoxypyridazine (SMP) and (Z-)-4-Bromo-5-(bromomethylene)-2(5H)-furanone
      (C30) to the bioluminescence of Aliivibrio fischeri (A. fischeri) and the CRC for
      independent action model with 95% confidence bands varied from low-concentration
      to higher-concentration regions in a timely manner expressed the joint toxic
      action of the mixture changing with an increase of both concentration and time.
      Through investigating the time-dependent hormetic effects of SMP and C30 (by
      measuring the expression of protein mRNA, simulating the bioluminescent reaction
      and analyzing the toxic action), the underlying mechanism was as follows: SMP and
      C30 acted on the quorum sensing (QS) system of A. fischeri, which induced low
      concentration stimulatory effects and high-concentration inhibitory effects; in
      the low-concentration region, the stimulatory effects of SMP and C30 made the
      mixture produce a synergistic stimulation on the bioluminescence; thus, the joint
      toxic action exhibited antagonism. In the high-concentration region, the
      inhibitory effects of SMP and C30 in the mixture caused a double block in the
      loop circuit of the QS system; thus, the joint toxic action exhibited synergism.
      With the increase of time, these stimulatory and inhibitory effects of SMP and
      C30 were changed by the variation of the QS system at different growth phases,
      resulting in the time-dependent cross-phenomenon. This study proposes an induced
      mechanism for time-dependent cross-phenomenon based on QS, which may provide new
      insight into the mechanistic investigation of time-dependent cross-phenomenon,
      benefitting the environmental risk assessment of mixtures.

PMID- 29471188
TI  - Developing, cross-validating and applying regression models to predict the
      concentrations of faecal indicator organisms in coastal waters under different
      environmental scenarios.
AB  - This study developed, cross-validated and applied a regression-based model to
      predict concentrations of faecal indicator organisms (FIOs) under different
      environmental conditions in the North and South bays of Santa Catarina, South of
      Brazil. The model was developed using a database of FIO concentrations in
      seawater sampled at 50 sites and the validation was performed using a different
      database by comparing 288 pairs of measured and modelled results for 15 sites.
      The index of agreement between the model outputs and the FIO concentrations
      measured during the validation period was 66%; the mean average error was 0.43
      log10 and the root mean square error was 0.58 log10 MPN.100mL-1. These validation
      results indicate that the model provides a fair representation of the FIO
      contamination in the bays for the meteorological conditions under which the model
      was trained. The simulation of different scenarios showed that under typical
      levels of resident human population in the catchments and median rainfall and
      solar radiation conditions, the median FIO concentration in the bays is 0.4
      MPN.100mL-1. Under extreme meteorological conditions, the combined effect of high
      rainfall and low solar radiation increased FIO concentrations up to 5 log10
      MPN.100mL-1. The simulated scenarios also show that increases in resident
      population during the summer tourist season and average rainfall concentrations
      do not increase median FIO concentrations in the bays relative to periods of time
      with average population, possibly because of higher bacterial die-off in the
      waters. The models can be an effective tool for management of human health risks
      in bathing and shellfish waters impacted by sewage pollution.

PMID- 29471189
TI  - Concentrations of trace elements and PCDD/Fs around a municipal solid waste
      incinerator in Girona (Catalonia, Spain). Human health risks for the population
      living in the neighborhood.
AB  - Previously to the modernization of the municipal solid waste incinerator (MSWI)
      of Campdora (Girona, Catalonia, Spain) two sampling campaigns (2015 and 2016)
      were conducted. In each campaign, 8 soil and 4 air samples (PM10 and total
      particle phase and gas phase) were collected. The levels of As, Cd, Co, Cr, Cu,
      Hg, Mn, Ni, Pb, Sb, Sn, Tl and V, and PCDD/Fs were analysed at different
      distances and wind directions around the MSWI. Environmental levels of trace
      elements and PCDD/Fs were used to assess exposure and health risks (carcinogenic
      and non-carcinogenic) for the population living around the facility. In soils, no
      significant differences were observed for trace elements and PCDD/Fs between both
      campaigns. In air, significant higher levels of As, Cd, Co, Mn, Ni, Pb, Tl and V
      were detected in 2016. Regarding soil levels, only Cd (distances) and As, Cu, Mn,
      and Ni (wind directions) showed significant differences. No differences were
      noted in the concentrations of trace elements and PCDD/Fs in air levels with
      respect to distances and directions to the MSWI. No differences were registered
      in air levels (elements and PCDD/Fs) between points influenced by MSWI emissions
      and background point. However some differences in congener profile were noted
      regarding from where back-trajectories come from (HYSPLIT model results),
      pointing some influence of Barcelona metropolitan area. The concentrations of
      trace elements and PCDD/Fs were similar -or even lower- than those reported
      around other MSWIs in Catalonia and various countries. Non-carcinogenic risks
      were below the safety limit (HQ<1). In turn, carcinogenic risks due to exposure
      to trace elements and PCDD/Fs were in acceptable ranges, according to national
      and international standard regulations.

PMID- 29471190
TI  - Interdecadal changes of summer aerosol pollution in the Yangtze River Basin of
      China, the relative influence of meteorological conditions and the relation to
      climate change.
AB  - Winter is a season of much concern for aerosol pollution in China, but less
      concern for pollution in the summertime. There are even less concern and larger
      uncertainty about interdecadal changes in summer aerosol pollution, relative
      influence of meteorological conditions, and their links to climate change. Here
      we try to reveal the relation among interdecadal changes in summer's most
      important circulation system affecting China (East Asian Summer Monsoon-EASM), an
      index of meteorological conditions (called PLAM, Parameter Linking Air Quality
      and Meteorological Elements, which is almost linearly related with aerosol
      pollution), and aerosol optical depth (AOD) in the middle and lower reaches of
      the Yangtze River (M-LYR) in central eastern China during summertime since the
      1960's. During the weak monsoon years, the aerosol pollution load was heavier in
      the M-LYR and opposite in the strong monsoon years mainly influenced by EASM and
      associated maintenance position of the anti-Hadley cell around 115 degrees E. The
      interdecadal changes in meteorological conditions and their associated aerosol
      pollution in the context of such climate change have experienced four periods
      since the 1960's, which were a relatively large decreased period from 1961 to
      1980, a large rise between 1980 and 1999, a period of slow rise or maintenance
      from 1999 to 2006, and a relatively rapid rise between 2006 and 2014. Among later
      three pollution increased periods, about 51%, 25% and 60% of the aerosol
      pollution change respectively come from the contribution of worsening weather
      conditions, which are found to be greatly affected by changes in EASM.

PMID- 29471191
TI  - Peak knee biomechanics and limb symmetry following unilateral anterior cruciate
      ligament reconstruction: Associations of walking gait and jump-landing outcomes.
AB  - BACKGROUND: Aberrant walking-gait and jump-landing biomechanics may influence the
      development of post-traumatic osteoarthritis and increase the risk of a second
      anterior cruciate ligament injury, respectively. It remains unknown if
      individuals who demonstrate altered walking-gait biomechanics demonstrate similar
      altered biomechanics during jump-landing. Our aim was to determine associations
      in peak knee biomechanics and limb-symmetry indices between walking-gait and jump
      landing tasks in individuals with a unilateral anterior cruciate ligament
      reconstruction. METHODS: Thirty-five individuals (74% women, 22.1 [3.4] years
      old, 25 [3.89] kg/m2) with an anterior cruciate ligament reconstruction performed
      5-trials of self-selected walking-gait and jump-landing. Peak kinetics and
      kinematics were extracted from the first 50% of stance phase during walking-gait
      and first 100 ms following ground contact for jump-landing. Pearson product
      moment (r) and Spearman's Rho (rho) analyses were used to evaluate relationships
      between outcome measures. Significance was set a priori (P <= 0.05). FINDINGS:
      All associations between walking-gait and jump-landing for the involved limb,
      along with the majority of associations for limb-symmetry indices and the
      uninvolved limb, were negligible and non-statistically significant. There were
      weak significant associations for instantaneous loading rate (rho = 0.39, P =
      0.02) and peak knee abduction angle (rho = 0.36, p = 0.03) uninvolved limb, as
      well as peak abduction displacement limb-symmetry indices (rho= - 0.39, p = 0.02)
      between walking-gait and jump-landing. INTERPRETATION: No systematic associations
      were found between walking-gait and jump-landing biomechanics for either limb or
      limb-symmetry indices in people with unilateral anterior cruciate ligament
      reconstruction. Individuals with an anterior cruciate ligament reconstruction who
      demonstrate high-involved limb loading or asymmetries during jump-landing may not
      demonstrate similar biomechanics during walking-gait.

PMID- 29471193
TI  - The value of tests evaluating visual functions in detecting overt or subclinical
      optic neuritis in multiple sclerosis.

PMID- 29471192
TI  - The effect of magnolol on Ca2+ homeostasis and its related physiology in human
      oral cancer cells.
AB  - OBJECTIVE: Magnolol, a polyphenol compound from herbal medicines, was shown to
      alter physiology in various cell models. However, the effect of magnolol on Ca2+
      homeostasis and its related physiology in oral cancer cells is unclear. This
      study examined whether magnolol altered Ca2+ signaling and cell viability in OC2
      human oral cancer cells. METHODS: Cytosolic Ca2+ concentrations ([Ca2+]i) in
      suspended cells were measured by using the fluorescent Ca2+-sensitive dye fura-2.
      Cell viability was examined by 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5
      tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1) assay.
      RESULTS: Magnolol at concentrations of 20-100 MUM induced [Ca2+]i rises. Ca2+
      removal reduced the signal by approximately 50%. Magnolol (100 MUM) induced Mn2+
      influx suggesting of Ca2+ entry. Magnolol-induced Ca2+ entry was partially
      suppressed by protein kinase C (PKC) regulators, and inhibitors of store-operated
      Ca2+ channels. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+
      pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished magnolol-evoked
      [Ca2+]i rises. Conversely, treatment with magnolol abolished BHQ-evoked [Ca2+]i
      rises. Inhibition of phospholipase C (PLC) with U73122 partially inhibited
      magnolol-induced [Ca2+]i rises. Magnolol at 20-100 MUM decreased cell viability,
      which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM).
      CONCLUSIONS: Together, in OC2 cells, magnolol induced [Ca2+]i rises by evoking
      partially PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+
      entry via PKC-sensitive store-operated Ca2+ entry. Magnolol also caused Ca2+
      independent cell death. Therefore, magnolol-induced cytotoxicity may not be
      involved in activation mechanisms associated with intracellular Ca2+ mobilization
      in oral cancer cells.

PMID- 29471194
TI  - Relationship between postural control and muscle activity during a handstand in
      young and adult gymnasts.
AB  - The aim of this study was to evaluate the relationship between muscle activity
      and inter-muscle contributions patterns and postural control during a handstand.
      Additionally, outcomes were compared between young and adult gymnasts (mean +/-
      SD: 13.9 +/- 0.7 and 23 +/- 3 years respectively). Participants performed three
      trials of a 10 s handstand on a force platform with simultaneous EMG signal
      recording at the upper and lower limbs. Adult gymnasts demonstrated significantly
      better postural control in each studied variable. The wrist flexors demonstrated
      the highest relative mean (60%) and peak (200%) EMG activity of all muscle groups
      studied. Wrist flexor activity was also highly correlated with postural control
      variables in both groups. The trapezius descendens and wrist flexor muscles
      demonstrated the highest contribution (20-26% and 25.5-28% respectively),
      followed by anterior deltoid (15-18%) and triceps brachii (13-16%) in both
      groups. The young gymnast group demonstrated significantly greater mean relative
      muscle activity at the triceps brachii, biceps brachii and rectus femoris
      compared with the adult group (88% (p = 0.023), 150% (p = 0.003) and 75% (p =
      0.039) respectively). To conclude, despite comparable inter-muscle contributions
      during a handstand, young and adult gymnasts demonstrated a different
      relationship between muscle activity and postural control variables.

PMID- 29471195
TI  - GXNOR-Net: Training deep neural networks with ternary weights and activations
      without full-precision memory under a unified discretization framework.
AB  - Although deep neural networks (DNNs) are being a revolutionary power to open up
      the AI era, the notoriously huge hardware overhead has challenged their
      applications. Recently, several binary and ternary networks, in which the costly
      multiply-accumulate operations can be replaced by accumulations or even binary
      logic operations, make the on-chip training of DNNs quite promising. Therefore
      there is a pressing need to build an architecture that could subsume these
      networks under a unified framework that achieves both higher performance and less
      overhead. To this end, two fundamental issues are yet to be addressed. The first
      one is how to implement the back propagation when neuronal activations are
      discrete. The second one is how to remove the full-precision hidden weights in
      the training phase to break the bottlenecks of memory/computation consumption. To
      address the first issue, we present a multi-step neuronal activation
      discretization method and a derivative approximation technique that enable the
      implementing the back propagation algorithm on discrete DNNs. While for the
      second issue, we propose a discrete state transition (DST) methodology to
      constrain the weights in a discrete space without saving the hidden weights.
      Through this way, we build a unified framework that subsumes the binary or
      ternary networks as its special cases, and under which a heuristic algorithm is
      provided at the website https://github.com/AcrossV/Gated-XNOR. More particularly,
      we find that when both the weights and activations become ternary values, the
      DNNs can be reduced to sparse binary networks, termed as gated XNOR networks
      (GXNOR-Nets) since only the event of non-zero weight and non-zero activation
      enables the control gate to start the XNOR logic operations in the original
      binary networks. This promises the event-driven hardware design for efficient
      mobile intelligence. We achieve advanced performance compared with state-of-the
      art algorithms. Furthermore, the computational sparsity and the number of states
      in the discrete space can be flexibly modified to make it suitable for various
      hardware platforms.

PMID- 29471196
TI  - Distant supervision for neural relation extraction integrated with word attention
      and property features.
AB  - Distant supervision for neural relation extraction is an efficient approach to
      extracting massive relations with reference to plain texts. However, the existing
      neural methods fail to capture the critical words in sentence encoding and
      meanwhile lack useful sentence information for some positive training instances.
      To address the above issues, we propose a novel neural relation extraction model.
      First, we develop a word-level attention mechanism to distinguish the importance
      of each individual word in a sentence, increasing the attention weights for those
      critical words. Second, we investigate the semantic information from word
      embeddings of target entities, which can be developed as a supplementary feature
      for the extractor. Experimental results show that our model outperforms previous
      state-of-the-art baselines.

PMID- 29471197
TI  - Extracting cardiac dynamics within ECG signal for human identification and
      cardiovascular diseases classification.
AB  - Cardiac characteristics underlying the time/frequency domain features are limited
      and not comprehensive enough to reflect the temporal/dynamical nature of ECG
      patterns. This paper proposes a dynamical ECG recognition framework for human
      identification and cardiovascular diseases classification via a dynamical neural
      learning mechanism. The proposed method consists of two phases: a training phase
      and a test phase. In the training phase, cardiac dynamics within ECG signals is
      extracted (approximated) accurately by using radial basis function (RBF) neural
      networks through deterministic learning mechanism. The obtained cardiac system
      dynamics is represented and stored in constant RBF networks. An ECG signature is
      then derived from the extracted cardiac dynamics along the periodic ECG state
      trajectories. A bank of estimators is constructed using the extracted cardiac
      dynamics to represent the trained gait patterns. In the test phase, recognition
      errors are generated and taken as the similarity measure by comparing the cardiac
      dynamics of the trained ECG patterns and the dynamics of the test ECG pattern.
      Rapid recognition of a test ECG pattern begins with measuring the state of test
      pattern, and automatically proceeds with the evolution of the recognition error
      system. According to the smallest error principle, the test ECG pattern can be
      rapidly recognized. This kind of cardiac dynamics information represents the beat
      to-beat temporal change of ECG modifications and the temporal/dynamical nature of
      ECG patterns. Therefore, the amount of discriminability provided by the cardiac
      dynamics is larger than the original signals. This paper further discusses the
      extension of the proposed method for cardiovascular diseases classification. The
      constructed recognition system can distinguish and assign dynamical ECG patterns
      to predefined classes according to the similarity of cardiac dynamics.
      Experiments are carried out on the FuWai and PTB ECG databases to demonstrate the
      effectiveness of the proposed method.

PMID- 29471198
TI  - Gaze patterns reveal how situation models and text representations contribute to
      episodic text memory.
AB  - When recalling something you have previously read, to what degree will such
      episodic remembering activate a situation model of described events versus a
      memory representation of the text itself? The present study was designed to
      address this question by recording eye movements of participants who recalled
      previously read texts while looking at a blank screen. An accumulating body of
      research has demonstrated that spontaneous eye movements occur during episodic
      memory retrieval and that fixation locations from such gaze patterns to a large
      degree overlap with the visuospatial layout of the recalled information. Here we
      used this phenomenon to investigate to what degree participants' gaze patterns
      corresponded with the visuospatial configuration of the text itself versus a
      visuospatial configuration described in it. The texts to be recalled were scene
      descriptions, where the spatial configuration of the scene content was
      manipulated to be either congruent or incongruent with the spatial configuration
      of the text itself. Results show that participants' gaze patterns were more
      likely to correspond with a visuospatial representation of the described scene
      than with a visuospatial representation of the text itself, but also that the
      contribution of those representations of space is sensitive to the text content.
      This is the first demonstration that eye movements can be used to discriminate on
      which representational level texts are remembered and the findings provide novel
      insight into the underlying dynamics in play.

PMID- 29471199
TI  - Statistical modelling of Fat, Oil and Grease (FOG) deposits in wastewater pump
      sumps.
AB  - The accumulation of FOG (Fat, Oil and Grease) deposits in sewer pumping stations
      results in an increase in maintenance costs, malfunctioning of pumps and, a
      potential increase of wastewater spills in receiving open water bodies. It is
      thought that a variety of parameters (e.g. geometry of the pump sump, pump
      operation, socioeconomic parameters of the catchment) influences the built-up of
      FOG. Based on a database containing data of 126 pumping stations located in five
      Dutch municipalities a statistical model was built. It is shown that 3 parameters
      are most significant in explaining the occurrence of FOG deposits: mean income of
      the population in a catchment, the amount of energy (kinetic and potential) per
      m3 per day and the density of restaurants, bars and hotels in a catchment.
      Further it is shown that there are significant differences between municipalities
      that can be traced back to the local 'design paradigm'. For example, in
      Amsterdam, the design philosophy of discharging in the pump sump under the water
      surface (and hence maintaining a low level of turbulence in the pump sump)
      results in an increase of the probability of the formation of FOG.

PMID- 29471200
TI  - A review on recent progress in the detection methods and prevalence of human
      enteric viruses in water.
AB  - Waterborne human enteric viruses, such as noroviruses and adenoviruses, are
      excreted in the feces of infected individuals and transmitted via the fecal-oral
      route including contaminated food and water. Since viruses are normally present
      at low concentrations in aquatic environments, they should be concentrated into
      smaller volumes prior to downstream molecular biological applications, such as
      quantitative polymerase chain reaction (qPCR). This review describes recent
      progress made in the development of concentration and detection methods of human
      enteric viruses in water, and discusses their applications for providing a better
      understanding of the prevalence of the viruses in various types of water
      worldwide. Maximum concentrations of human enteric viruses in water that have
      been reported in previous studies are summarized to assess viral abundances in
      aquatic environments. Some descriptions are also available on recent applications
      of sequencing analyses used to determine the genetic diversity of viral genomes
      in water samples, including those of novel viruses. Furthermore, the importance
      and significance of utilizing appropriate process controls during viral analyses
      are discussed, and three types of process controls are considered: whole process
      controls, molecular process controls, and (reverse transcription (RT)-)qPCR
      controls. Although no standards have been established for acceptable values of
      virus recovery and/or extraction-(RT-)qPCR efficiency, use of at least one of
      these appropriate control types is highly recommended for more accurate
      interpretation of observed data.

PMID- 29471201
TI  - Facile synthesis of Bi2MoO6/reduced graphene oxide composites as anode materials
      towards enhanced lithium storage performance.
AB  - Bi2MoO6/reduced graphene oxide (Bi2MoO6/rGO) composites were fabricated by a
      facile one-pot hydrothermal approach, in which Bi2MoO6 nanosheets and rGO were
      simultaneously obtained. The structure and composition of the as-synthesized
      Bi2MoO6 and Bi2MoO6/rGO materials were characterized via FT-IR, BET, TGA, XRD,
      TEM, SEM and XPS analyses, and the electrochemical performance of Bi2MoO6/rGO as
      an anode in a lithium-ion battery was investigated. Compared with pristine
      Bi2MoO6, the Bi2MoO6/rGO composites have higher capacities, better cycle
      stability and higher rates. For a current density of 100 mA g-1, the initial
      discharge capacities of the Bi2MoO6/rGO-20 and pristine Bi2MoO6 were 1049.6 mAh g
      1 and 528.5 mAh g-1, respectively. After 100 cycles, the capacity retention for
      the Bi2MoO6/rGO-20 and pristine Bi2MoO6 were respectively 80.4% and 30.7% using
      the 2nd cycle capacities (895.8 and 402.4 mAh g-1) as references. The enhanced
      electrochemical performance can be ascribed to the synergistic effect of the
      Bi2MoO6 and rGO sheets, which dramatically improves the conductivities of the
      Bi2MoO6/rGO anodes. In addition, the rGO sheets also supply electron transfer
      routes for the anode and suppress volume changes of Bi2MoO6 nanosheets during the
      charge-discharge cycles.

PMID- 29471202
TI  - Conductive micropatterned polyurethane films as tissue engineering scaffolds for
      Schwann cells and PC12 cells.
AB  - Controlling cellular alignment and elongation has been demonstrated as an
      important parameter for developing nerve tissue engineering scaffolds. Many
      approaches have been developed to guide cellular orientation for nerve
      regeneration such as micropatterning techniques. However, most of materials used
      for developing micropatterning scaffolds lack of bioactivity and
      biofunctionability. Here we present a functional conductive micropatterned
      scaffold based on bioactive conductive biodegradable polyurethane prepared using
      a micro-molding technique. These conductive micropatterned scaffolds are able to
      not only induce the Schwann cells (SCs) alignment and elongation by the
      micropatterned surface but also enhance the nerve growth factor (NGF) gene
      expression of SCs by the bioactivity of these materials. Additionally, the
      combined effect of the bioactivity of such conductive materials and the
      micropatterned structure also dramatically promotes the neurite extension and
      elongation of PC12 cells in a highly aligned direction. These data suggest that
      these conductive micropatterned scaffolds that easily control cellular
      orientation and organization, and dramatically enhance NGF gene expression and
      significantly induce the neurite extension of PC12 cells, have a great potential
      for nerve regeneration applications.

PMID- 29471203
TI  - Significance of an in-situ generated boundary film on tribocorrosion behavior of
      polymer-metal sliding pair.
AB  - Polymer composites have a high potential for applications as tribo-materials
      exposed to sea water owing to their self-lubrication characteristic and high
      chemical stability. In the present work, tribological behaviors of
      polyetheretherketone (PEEK) composites rubbing with stainless steel in sea water
      were explored using a pin-on-disc tribometer integrated with a potentiostat for
      electrochemical control. It was demonstrated that further adding 5 vol% hexagonal
      boron nitride (h-BN) nanoparticles into PEEK reinforced with short carbon fibers
      (SCF) significantly enhanced the wear resistance. Moreover, the stainless steel
      exhibited significantly enhanced tribocorrosion resistance when rubbing with the
      hybrid nanocomposite, in comparison to the sliding against PEEK filled only with
      SCF. Nanostructures of the boundary films formed on the steel surface were
      comprehensively investigated. It was manifested that tribo-chemistry products of
      h-BN, i.e. H3BO3 and B2O3, were arrayed in a closely packed boundary film. It
      seems that inclusion of layer-structured H3BO3 and B2O3 improved the resilience
      of the boundary film. The continuous boundary film covering the steel surface
      provided a lubrication effect and strengthened the passivation layer. A new route
      for enhancing simultaneously tribological and corrosion resistance of polymer
      metal pairs by controlling in-situ tribo-chemistry was thus proposed.

PMID- 29471204
TI  - Fabrication of a solution-gated transistor based on valinomycin modified iron
      oxide nanoparticles decorated zinc oxide nanorods for potassium detection.
AB  - There are considerable interests to detect and monitor the abnormal level of
      minerals in water for avoiding/preventing any toxic effects after consumption.
      Herein, we report the fabrication of solution-gated field-effect-transistor (FET)
      based potassium sensor using iron oxide nanoparticles (Fe2O3 NPs) modified
      directly grown zinc oxide nanorods (ZnO NRs). The Fe2O3 NPs modification of ZnO
      NRs provided stability to nanorods surface and improved surface area for
      valinomycin immobilization. As-fabricated potassium sensor (valinomycin-Fe2O3 NPs
      ZnO NRs/SiO2/Si) provided enhanced current response with increasing potassium
      concentration. During sensing measurements, FET sensor showed high sensitivity
      (4.65 MUA/MUM/cm2) in the linear range of 0.1 MUM to 125 MUM, low limit of
      detection (~0.04 MUM), good stability, excellent reproducibility, and favorable
      selectivity. Thus, good sensing performance of the FET based potassium sensor
      presents it as simple, low-cost, and convenient device for selective detection of
      potassium in solution.

PMID- 29471205
TI  - Fabrication of bioinspired, self-cleaning superliquiphilic/phobic stainless steel
      using different pathways.
AB  - The mechanical properties, corrosion-resistance, and aesthetics of stainless
      steel make it one of the most important and widely used materials worldwide in
      the construction, food, and transportation industries just to name a few. In this
      paper we demonstrate how these properties can be further enhanced by changing the
      hydrophilic stainless steel surface to be superhydrophilic, superhydrophobic, or
      superliquiphobic. Creation of these functional surfaces requires hierarchical
      roughness and chemistry. Roughness is created using various pathways including
      sandblasting, chemical etching, and nanocomposite coatings. Surface chemistry is
      controlled using methylchlorosilane, nanoparticles in methylphenyl silicone, and
      fluorosilane treatment. The broad approach allows for direct comparisons of these
      pathways. Resulting treatments can create stainless steel surfaces with a
      hexadecane contact angle of 155 degrees  and tilt angle of 7-10 degrees .
      Discussions of rust-avoidance and coating through condensation reactions are
      included. Enhanced properties of self-cleaning behavior, anti-icing behavior,
      wear resistance, and bending resistance are demonstrated on stainless steel 304
      L. Stainless steel 430, which is more corrosion prone than stainless steel 304 L,
      is then used to demonstrate transferability of the treatments and corrosion
      resistance imparted through superliquiphobicity.

PMID- 29471206
TI  - State-trait anxiety levels during pregnancy and foetal parameters following
      intervention with music therapy.
AB  - BACKGROUND: Research indicates that anxiety during pregnancy may be a risk factor
      for the development of alterations in the mental health of the pregnant woman and
      of obstetric complications. OBJECTIVE: to investigate the effect of music therapy
      on maternal anxiety, before and after a non-stress test (NST), and the effect of
      maternal anxiety on the birthing process and birth size. METHODS: 409 nulliparous
      women coming for routine prenatal care were randomized in the third trimester to
      receive either music therapy (n = 204) or no music therapy (n = 205) during an
      NST. Maternal anxiety was assessed using the Spielberger State-Trait Anxiety
      Inventory before and after the NST. RESULTS: After the NST, the women from the
      music group showed significantly lower scores in state anxiety (OR = 0.87; p <
      0.001) as well as trait anxiety (p < 0.001) than the control group. Furthermore,
      the pregnant women from the music group presented lower levels of state-trait
      anxiety than the control group in relation to the variables of birth process, and
      higher birth weight and chest circumference in the newborn (OR = 3.5 and OR =
      0.81, respectively; p < 0.05). LIMITATIONS: This study was limited by the fact
      that it was a single-centre study; the observers conducting the NST were not
      blinded to the allocation, although neither midwife had any knowledge of the
      maternal anxiety scores, and we could not apply the double-blind method due to
      the nature of the observation. CONCLUSIONS: Our findings confirm that music
      therapy intervention during pregnancy could reduce elevated state-trait anxiety
      levels during the third trimester. Further research into the influence of music
      therapy as intervention on maternal anxiety and on the birthing process and birth
      size is required during pregnancy.

PMID- 29471207
TI  - Locomotive function and quality of life among older people in Liaoning, China:
      Falls efficacy as mediator or moderator?
AB  - OBJECTIVES: This study aimed to examine the role of falls efficacy in the
      relationship between the locomotive function and quality of life. METHODS: From
      March to May in 2016, we conducted a cross-sectional survey among 830 community
      residents aged >=60 years from Jinzhou,China.GLFS-25 (25-question Geriatric
      Locomotive Function Scale), FES-I(International edition of Falls Efficacy
      Scale),and SF-12 (12-item Short Form Health Survey) were used to estimate
      locomotive function, falls efficacy and quality of life, respectively. The higher
      score of GLFS-25, the worse the locomotive function. RESULTS: Median age was
      68.69 years (ranges 60-88). Locomotive function, falls efficacy and quality of
      life all presented a linear relationship within each other, locomotive function
      score was negatively correlated with falls efficacy score (-0.461, P < 0.01).
      locomotive function score was negatively correlated with quality of life score (
      0.523, P < 0.01).Falls efficacy score was positively correlated with quality of
      life score (0.415, P < 0.01).Falls efficacy exerted both a mediating and
      moderating role between locomotive function and quality of life, and the
      mediation effect accounted for 45.5% of the total effect. CONCLUSIONS: Poorer
      locomotive function was associated with poorer quality of life, and greater falls
      efficacy was associated with better quality of life. In addition, falls efficacy
      was demonstrated to be both a mediator and moderator variable in the linkage
      between locomotive function and quality of life. Aged care professional
      practitioners and our policy makers should strengthen the awareness of the
      psychological role of the elderly falls efficacy.

PMID- 29471208
TI  - Understanding biopharmaceutical production at single nucleotide resolution using
      ribosome footprint profiling.
AB  - Biopharmaceuticals such as monoclonal antibodies have revolutionised the
      treatment of a variety of diseases. The production of recombinant therapeutic
      proteins, however, remains expensive due to the manufacturing complexity of
      mammalian expression systems and the regulatory burden associated with
      administrating these medicines to patients in a safe and efficacious manner. In
      recent years, academic and industrial groups have begun to develop a greater
      understanding of the biology of host cell lines, such as Chinese hamster ovary
      (CHO) cells and utilise that information for process development and cell line
      engineering. In this review, we focus on ribosome footprint profiling (RiboSeq),
      an exciting next generation sequencing (NGS) method that provides genome-wide
      information on translation, and discuss how its application can transform our
      understanding of therapeutic protein production.

PMID- 29471209
TI  - Genetic engineering of host organisms for pharmaceutical synthesis.
AB  - Pharmaceutical production hosts may be derived from almost any organism, from
      Chinese Hamster Ovary (CHO) cell lines to isolated actinomycetes. Each host can
      be improved, historically only through adaptive evolution. Recently, the
      maturation of organism engineering has expanded the available models, methods,
      and tools for altering host phenotypes. New tools like CRISPR-associated
      endonucleases promise to enable precise cellular reprogramming and to access
      previously intractable hosts. In this review, we discuss the most recent advances
      in engineering several types of pharmaceutical production hosts. These include
      model organisms, potential platform hosts with advantageous metabolism or
      physiology, specialized producers capable of unique biosynthesis, and CHO, the
      most widely used recombinant protein production host. To realize improved
      engineered hosts, an increasing number of approaches involving DNA sequencing and
      synthesis, host rewriting technologies, computational methods, and organism
      engineering strategies must be used. Integrative workflows that enable
      application of the right combination of methods to the right production host
      could enable economical production solutions for emerging human health
      treatments.

PMID- 29471210
TI  - Reply to: The effect of bariatric surgery on direct-acting oral anticoagulant
      drug levels.

PMID- 29471211
TI  - Exogenous nanosilica improves germination and growth of cucumber by maintaining
      K+/Na+ ratio under elevated Na+ stress.
AB  - The current work was aimed to elucidate the role of engineered nanosilica (SiNPs)
      particles to mitigate the damaging impacts of Na+-derived salinity on cucumber
      (Cucumis sativus) Beit Alpha variety by conducting in vitro experiments applying
      various Na+ concentrations i.e. 0, 1000, 2000, 3000, 4000 and 5000 mg L-1. By
      treating seeds and seedlings, respectively, of cucumber with SiNPs (0, 100, 200
      and 300 ppm) and subsequent determination some germination and vegetative
      parameters as well as chemical analysis of seedlings, we verified that SiNPs
      succeeded to alleviate the detrimental effects of high Na+ salinity by increasing
      germination parameters and vegetative growth of cucumber seedlings. Even as
      little as 100 ppm of N-Si results in considerable improvement of seed germination
      and seedlings growth of cucumber compared to the control, while 200 ppm was
      optimal among the doses tested. At 5000 mg Na+ L-1, applying SiNPs with 200 ppm
      increased final germination percentage by 101% over control, vigor index by 101%,
      germination rate index by 116%, germination index by 110%, fresh mass by 13%,
      K+/Na+ ratio by 77%, shoot dry mass by 384%, root dry mass by 304% and plant
      height by 70%. The results mentioned in this paper obviously outline the large
      practical relevance of SiNPs and imply that applying of SiNPs for cucumber seeds
      and seedlings under high Na+-derived salinity enhances germination and growth as
      a result for decreasing Na+ uptake and sequentially improves high K+/Na+ ratio.

PMID- 29471212
TI  - Nodular fasciitis mimicking a soft tissue sarcoma - A case report.
AB  - INTRODUCTION: Nodular Fasciitis, also known as infiltrative or pseudosarcomatous
      fasciitis, is a benign soft tissue tumour of fibroblastic/myofibroblastic
      differentiation, that was first described in 1955 by Konwaler et al. PRESENTATION
      OF CASE: This is a case report of a 27-year old male with complaints of a
      swelling in the right axilla for 2 and 1/2 years measuring 12 cm * 10 cm. Chest X
      Ray was normal. Magnetic Resonance Imaging of the right arm and chest showed an
      irregular mass in the axilla in the muscular-subcutaneous plane measuring 10.8 cm
      * 8.8 cm * 12 cm, with no neural involvement. Magnetic Resonance Angiogram showed
      feeders from the branches of the Right Subclavian and Right Axillary Artery and
      venous drainage into the Right Subclavian Vein. USG guided biopsy was done which
      showed benign spindle cell neoplasm. Patient underwent wide local excision under
      general anesthesia. The specimen was sent for histopathological examination which
      showed histological and immunohistochemical features in favour of Nodular
      Fasciitis. DISCUSSION: Most nodular fasciitis lesions are solitary and occur in
      adults 20-40 years of age. Nodular fasciitis affects both men and women with
      equal frequency. Differential diagnosis of nodular fasciitis includes,
      fibrosarcoma, fibroma, fibrous histiocytoma, and desmoids and histopathology and
      immunohistochemistry play a key role in identifying the condition. CONCLUSION:
      Owing to the size, location and findings of the Magnetic Resonance Angiogram we
      initially suspected a Soft Tissue Sarcoma, but to our surprise, on further
      investigation the mass was revealed to be Nodular Fasciitis.

PMID- 29471213
TI  - Cerebellar gray matter explains bimanual coordination performance in children and
      older adults.
AB  - The cerebellum appears to undergo late maturation in children and early decline
      at older age. Whether these age-related changes affect bimanual coordination
      performance remains unclear at best. Here, we identified the ages at which
      bimanual coordination performance stops improving and starts declining. In an
      independent cohort, we defined brain regions of interest involved in bimanual
      coordination using functional magnetic resonance imaging. We used these regions
      of interest to investigate the extent to which the gray matter of cerebellar and
      other brain regions explains bimanual coordination performance from 10- to 80
      year-olds. Results showed that bimanual coordination performance starts declining
      from the age of 40 years. In participants aged 10-20 years, cerebellar lobule VI
      was the only significant brain predictor of bimanual coordination performance. In
      participants aged 60-80 years, this cerebellar region, together with the primary
      sensorimotor cortex, formed a group of strongest predictors. These results from 2
      independent samples (10-20 and 60-80 years) suggest that cerebellar lobule VI is
      critical for the development and preservation of bimanual coordination skills in
      children and older adults, respectively. In addition, post hoc analyses suggested
      that the primary motor cortex mediated the adverse effect of age on bimanual
      coordination performance in older adults.

PMID- 29471216
TI  - Toward true closed-loop neuromodulation: artifact-free recording during
      stimulation.
AB  - Closed-loop and responsive neuromodulation systems improve open-loop
      neurostimulation by responding directly to measured neural activity and providing
      adaptive, on-demand therapy. To be effective, these systems must be able to
      simultaneously record and stimulate neural activity, a task made difficult by
      persistent stimulation artifacts that distort and obscure underlying biomarkers.
      To enable simultaneous stimulation and recording, several techniques have been
      proposed. These techniques involve artifact-preventing system configurations,
      resilient recording front-ends, and back-end signal processing for removing
      recorded artifacts. Co-designing and integrating these artifact cancellation
      techniques will be key to enabling neuromodulation systems to stimulate and
      record at the same time. Here, we review the state-of-the-art for these
      techniques and their role in achieving artifact-free neuromodulation.

PMID- 29471214
TI  - Joint associations of beta-amyloidosis and cortical thickness with cognition.
AB  - In 1164 cognitively unimpaired persons, aged 50-95 years, from the population
      based Mayo Clinic Study of Aging, we examined the relationships of baseline
      cognition and cognitive changes across the full range of cortical thickness of an
      Alzheimer signature region of interest and global beta-amyloid levels measured by
      Pittsburgh compound B positron emission tomography (PIB PET) standardized uptake
      value ratio (SUVR). In machine-learning models accounting for both biomarkers
      simultaneously, worsening biomarker values were additive and associated with
      lower baseline global cognition and greater subsequent decline in global
      cognition. Associations between Alzheimer's disease signature cortical thickness
      or PIB PET beta-amyloid SUVR and baseline cognition were mainly linear. Lower
      Alzheimer's disease signature cortical thickness values across the entire range
      of thickness predicted future decline in global cognitive scores, demonstrating
      its close relationship to cognitive functioning. PIB PET beta-amyloid SUVR also
      predicted cognitive decline across its full range, even when cortical thickness
      was accounted for. PIB PET beta-amyloid's relationship to cognitive decline was
      nonlinear, more prominent at lower beta-amyloid levels and less prominent at
      higher beta-amyloid levels.

PMID- 29471215
TI  - Genetic approaches to access cell types in mammalian nervous systems.
AB  - Understanding brain circuit organization and function requires systematic
      dissection of its cellular components. With vast cell number and diversity,
      mammalian nervous systems present a daunting challenge for achieving specific and
      comprehensive cell type access-prerequisite to circuit analysis. Genetic
      approaches in the mouse have relied on germline engineering to access marker
      defined cell populations. Combinatorial strategies that engage marker
      intersection, anatomy and projection pattern (e.g. antero-grade and retro-grade
      viral vectors), and developmental lineage substantially increase the specificity
      of cell type targeting. While increasing number of mouse cell types are becoming
      experimentally accessible, comprehensive coverage requires larger coordinated
      efforts with strategic infrastructural and fiscal planning. CRISPR-based genome
      editing may enable cell type access in other species, but issues of time, cost
      and ethics remain, especially for primates. Novel approaches that bypass the
      germline, such as somatic cell engineering and cell surface-based gene delivery,
      may reduce the barrier of genetic access to mammalian cell types.

PMID- 29471217
TI  - How gender norms are reinforced through violence against adolescent girls in two
      conflict-affected populations.
AB  - Violence against women and girls is a global concern, and particularly salient in
      humanitarian settings. Successful efforts to prevent gender-based violence in
      humanitarian settings must address a wide range of issues, from discriminatory
      laws to explicit community support for violence, and yet, at the core of these
      efforts is reducing oppressive gender and social norms. This study examined local
      attitudes towards and social norms around responding to physical and sexual abuse
      of girls through interviews conducted with adolescent girls (n = 66) and with
      caregivers (n = 58) among two conflict-affected populations: villages in South
      Kivu in the Democratic Republic of the Congo and Sudanese and South Sudanese
      refugees in Ethiopian camps. The findings suggest how communities use violence as
      a tool to enforce the importance of girls practicing community-defined "good"
      adolescent girl behavior, and have implications for gender-based violence
      programming among other conflict-affected populations.

PMID- 29471218
TI  - Albumin-covered lipid nanocapsules exhibit enhanced uptake performance by breast
      tumor cells.
AB  - Liquid lipid nanocapsules (LLN) represent a promising new generation of drug
      delivery systems. They can carry hydrophobic drugs in their oily core, but the
      composition and structure of the surrounding protective shell determine their
      capacity to survive in the circulatory system and to achieve their goal:
      penetrate tumor cells. Here, we present a study of LLN covered by the protein
      human serum albumin (HSA) and loaded with curcumin as a hydrophobic model drug. A
      cross-linking procedure was performed to further strengthen the protective
      protein layer. Physicochemical properties and release kinetics of the
      nanocapsules were investigated, and cellular uptake and killing capacity were
      evaluated on the human breast-cancer line MCF-7. The nanocapsules exhibited a
      half maximal inhibitory concentration (IC50) capacity similar to that of free
      curcumin, but avoiding problems associated with excipients, and displayed an
      outstanding uptake performance, entering cells massively in less than 1 min.

PMID- 29471219
TI  - The effects of extrinsic factors on the structural and mechanical properties of
      Pseudomonas fluorescens biofilms: A combined study of nutrient concentrations and
      shear conditions.
AB  - The growth of biofilms on surfaces is a complicated process influenced by several
      environmental factors such as nutrient availability and fluid shear. In this
      study, combinations of growth conditions were selected for the study of
      Pseudomonas fluorescens biofilms including as cultivation time (24- or 48 h),
      nutrient levels (1:1 or 1:10 King B medium), and shear conditions (75 RPM
      shaking, 0.4 mL min -1 or 0.7 mL min -1). The use of Confocal Laser Scanning
      Microscopy (CLSM) determined biofilm structure, while liquid-phase Atomic Force
      Microscopy (AFM) techniques resolved the mechanical properties of biofilms. Under
      semi-static conditions, high nutrient environments led to more abundant biofilms
      with three times higher EPS content compared to biofilms grown under low nutrient
      conditions. AFM results revealed that biofilms formed under these conditions were
      less stiff, as shown by their Young's modulus values of 2.35 +/- 0.08 kPa,
      compared to 4.98 +/- 0.02 kPa for that of biofilms formed under low nutrient
      conditions. Under dynamic conditions, however, biofilms exposed to low nutrient
      conditions and high shear rates led to more developed biofilms compared to other
      tested dynamic conditions. These biofilms were also found to be significantly
      more adhesive compared to their counterparts grown at higher nutrient conditions.

PMID- 29471220
TI  - An investigation of konjac glucomannan-keratin hydrogel scaffold loaded with
      Avena sativa extracts for diabetic wound healing.
AB  - We have developed a novel hydrogel composed of konjac glucomannan (KGM), human
      hair proteins (KER), and an ethanolic extract of Avena sativa (OAT) and evaluated
      its potential as a dressing material for diabetic wounds. KGM is an excellent
      biocompatible gelling agent that stimulates fibroblast proliferation and
      immunomodulation. Human hair proteins (KER) are biocompatible, biodegradable, and
      possess abundant cell adhesion sites. KER also promotes fibroblast attachment and
      proliferation, keratinocyte migration, and collagen expression, which can
      accelerate wound healing. OAT consists of oat beta-glucans and several anti
      inflammatory and antioxidant moieties that can reduce prolonged inflammation in
      chronic wounds. SEM images confirm the highly porous architecture of the
      scaffolds. When immersed in PBS, KGM+KER+OAT hydrogels absorb 7.5 times their dry
      weight. These hydrogels display a measured rate of degradation in lysozyme.
      KGM+KER+OAT hydrogels showed no significant cytotoxicity against NIH/3T3
      fibroblasts. DAPI and SEM images obtained after 48h of cell culture illustrate
      the attachment and infiltration of fibroblasts. In vivo studies performed using a
      diabetic rat excision wound model showed that KGM+KER+OAT hydrogels significantly
      accelerated wound healing compared to the control and the KGM+KER hydrogels.

PMID- 29471221
TI  - Estimating the Minimal Important Difference for the Western Ontario Rotator Cuff
      Index (WORC) in adults with shoulder pain associated with partial-thickness
      rotator cuff tears.
AB  - BACKGROUND: Knowledge about Minimal Important Differences (MIDs) is essential for
      the interpretation of continuous outcomes, especially patient-reported outcome
      measures (PROMS). OBJECTIVE: The aim of this study was to estimate the MID for
      the Western Ontario Rotator Cuff Index (WORC: score 0 (best) to 2100 (worst
      disability)) in adults with shoulder pain associated with partial-thickness
      rotator cuff tears, 'symptomatic PTTs', undergoing conservative treatment with
      physiotherapy. DESIGN: A prospectively-designed anchor-based MID analysis using
      data from a prospective prognostic study with a three-month follow-up conducted
      within an outpatient care setting in Germany. METHODS: The MID was estimated
      using data from 64 adults with atraumatic symptomatic PTTs who underwent three
      months of conservative treatment with physiotherapy. The anchor was a seven-point
      Global Perceived Change (GPC) scale. RESULTS: Based on a definition of the MID
      being the threshold of "being (at least slightly) improved" with a probability
      nearest to 0.90 (i.e. 9 of 10 patients achieving the MID), the MID for the WORC
      was estimated as -300 for 'improved' shoulder-related disability in 9 out of 10
      patients (95% CI 8 out of 10 patients to everyone) undergoing three months of
      exercise-based physiotherapy for symptomatic PTTs. CONCLUSIONS: This is the first
      published MID estimate for the WORC in adults with symptomatic PTTs of the
      rotator cuff undergoing typical treatment comprising conservative treatment with
      physiotherapy. The conceptual framework for interpretation facilitates its use in
      similar clinical contexts.

PMID- 29471222
TI  - Clinical experience with indigenous kit-based preparation of 68Ga-DOTATOC using
      commercial 68Ge/68Ga generator.
AB  - Pharmaceutical grade DOTATOC kits compliant with all the quality control criteria
      were formulated and radiolabeled with 68Ga in high yields. Comparison with module
      based 68Ga-DOTATOC established product equivalency. Clinical utility was
      evaluated in patients with histopathologically confirmed well-differentiated
      neuroendocrine tumors. Kit-based preparation of 68Ga-DOTATOC could identify sites
      of primary and metastatic disease. PET/CT images of patients conformed to the
      established criteria for somatostatin imaging agents and clinical expectations.
      Results of this study emphasize the potential of kit-based 68Ga-DOTATOC for PET
      imaging of neuroendocrine tumors.

PMID- 29471223
TI  - Indirect calculation of monoclonal antibodies in nanoparticles using the
      radiolabeling process with technetium 99 metastable as primary factor:
      Alternative methodology for the entrapment efficiency.
AB  - The use of monoclonal antibodies (Mab) in the current medicine is increasing.
      Antibody-drug conjugates (ADCs) represents an increasingly and important modality
      for treating several types of cancer. In this area, the use of Mab associated
      with nanoparticles is a valuable strategy. However, the methodology used to
      calculate the Mab entrapment, efficiency and content is extremely expensive. In
      this study we developed and tested a novel very simple one-step methodology to
      calculate monoclonal antibody entrapment in mesoporous silica (with magnetic
      core) nanoparticles using the radiolabeling process as primary methodology. The
      magnetic core mesoporous silica were successfully developed and characterised.
      The PXRD analysis at high angles confirmed the presence of magnetic cores in the
      structures and transmission electron microscopy allowed to determine structures
      size (58.9 +/- 8.1 nm). From the isotherm curve, a specific surface area of 872
      m2/g was estimated along with a pore volume of 0.85 cm3/g and an average pore
      diameter of 3.15 nm. The radiolabeling process to proceed the indirect
      determination were well-done. Trastuzumab were successfully labeled (>97%) with
      Tc-99m generating a clear suspension. Besides, almost all the Tc-99m used
      (labeling the trastuzumab) remained trapped in the surface of the mesoporous
      silica for a period as long as 8 h. The indirect methodology demonstrated a high
      entrapment in magnetic core mesoporous silica surface of Tc-99m-traztuzumab. The
      results confirmed the potential use from the indirect entrapment efficiency
      methodology using the radiolabeling process, as a one-step, easy and cheap
      methodology.

PMID- 29471224
TI  - Quantification of desoxyrhapontigenin (4-methoxyresveratrol) in rat plasma by LC
      MS/MS: Application to pre-clinical pharmacokinetic study.
AB  - Desoxyrhapontigenin (DRG, 4-methoxyresveratrol or trans-3,5-dihydroxy-4'
      methoxystilbene) is a naturally occurring resveratrol (RES) derivative with a
      variety of biological activities. To facilitate its further medicinal
      exploration, a reliable LC-MS/MS method was developed and validated for the
      quantification of DRG in rat plasma using heavy isotope labelled RES as an
      internal standard. The ESI was operated in its negative ion mode while DRG and
      RES were determined by multiple reaction monitoring (MRM) using precursor-to
      product ion transitions of m/z 241.1 -> 180.8 and m/z 233.0 -> 191.0,
      respectively. This LC-MS/MS method displayed excellent selectivity, sensitivity
      (LLOQ = 2.5 ng/ml), accuracy (both intra- and interday mean analytical recovery
      within 100 +/- 15%) and precision (both intra- and interday CV < 15%). The mean
      matrix factors were all within 1.000 +/- 0.150 with CV < 15%. The pharmacokinetic
      profiles of DRG were subsequently examined in Sprague-Dawley rats. Upon
      intravenous administration (4 or 10 mg/kg), DRG displayed very rapid clearance
      (Cl = 338 +/- 66 or 275 +/- 30 ml/min/kg) and short mean residence time (MRT =
      12.9 +/- 4.7 or 10.4 +/- 0.5 min). After oral administration of DRG fully
      solubilized by 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD), the plasma
      profiles of DRG were highly erratic with a low absolute bioavailability (F < 9.83
      +/- 5.31%). When DRG was given at a higher dose (50 mg/kg) in suspension form,
      the F was increased to 24.1 +/- 5.6%. The pharmacokinetic comparison among DRG,
      RES and some of its hydroxyl analogues stilbenes was performed. The information
      obtained from this study will facilitate further exploration on DRG as well as
      other RES derivatives.

PMID- 29471225
TI  - Location, location, location: Assessing the spatial patterning between marijuana
      licenses, alcohol outlets and neighborhood characteristics within Washington
      state.
AB  - BACKGROUND: The availability of marijuana products is becoming increasingly
      prevalent across the United States (US), many states are allowing for the
      production, processing, and retailing of these products for medical and/or
      recreational use. The purpose of this study is to: (1) examine the spatial
      patterning of marijuana licenses, and (2) examine the impact of alcohol outlets
      in addition to other neighborhood characteristics on marijuana licenses within
      the state of Washington. METHODS: This cross-sectional observational study
      examined 1458 census tracts in Washington state from 2017, using marijuana and
      alcohol data from the Washington State Liquor and Cannabis Board as well as
      neighborhood characteristics data from the American Community Survey 2011-2015 5
      year estimates. We used exploratory and formal spatial regression methods,
      including integrated nested Laplace approximation within a Bayesian statistical
      framework, to address the study aims. RESULTS: Our results indicate there is
      significant spatial patterning of marijuana producers and processors across the
      state. We also found that all marijuana licenses are located in poorer census
      tracts, and marijuana retailers are co-located in census tracts with off-premises
      alcohol outlets. CONCLUSIONS: Our study provides empirical evidence of the
      relationship between marijuana licenses, alcohol outlets, and neighborhood
      characteristics, and has important implications for policymakers in other states
      currently considering legalizing marijuana-products for medical and/or
      recreational use.

PMID- 29471226
TI  - Examining effects of medical cannabis narratives on beliefs, attitudes, and
      intentions related to recreational cannabis: A web-based randomized experiment.
AB  - BACKGROUND: This experimental study tests effects of exposure to video narratives
      about successful symptom relief with Medical Cannabis (MC) on attitudes, beliefs,
      and intentions related to recreational cannabis use. METHODS: Patient video
      testimonials were modeled after those found in extant media coverage. Israeli
      participants (N = 396) recruited through an online survey company were randomly
      assigned to view a narrative or a non-narrative video containing equivalent
      information about MC. Video content was further manipulated based on whether the
      protagonist had a stigmatized disease or not, and whether attribution of
      responsibility for his disease was internal or external. RESULTS: Exposure to
      patient testimonials indirectly increased positive attitudes, beliefs and
      intentions related to recreational cannabis use through changing attitudes,
      beliefs and intentions related to MC. Furthermore, exposure to narratives in
      which the patient was presented as not to blame for contracting his illness
      (external attribution) was associated with more positive attitudes, beliefs and
      intentions toward MC, a factor that was significantly associated with more
      positive attitudes, beliefs and intentions related to recreational cannabis use.
      CONCLUSIONS: These results suggest that narrative news media coverage of MC may
      influence public attitudes toward recreational cannabis. Because such media
      stories continue to be commonplace, it is important to examine potential
      spillover effects of this coverage on public perceptions of recreational
      cannabis. Cannabis prevention programs should address the role of media coverage
      in shaping public opinion and address the distinction between medical and
      recreational cannabis use.

PMID- 29471227
TI  - The impact of acute and short-term methamphetamine abstinence on brain
      metabolites: A proton magnetic resonance spectroscopy chemical shift imaging
      study.
AB  - BACKGROUND: Abuse of methamphetamine (MA) is a global health concern. Previous 1H
      MRS studies have found that, with methamphetamine abstinence (MAA), there are
      changes in n-acetyl-aspartate (NAA/Cr), myo-inositol (mI/Cr), choline (Cho/Cr and
      Cho/NAA), and glutamate with glutamine (Glx) metabolites. Limited studies have
      investigated the effect of acute MAA, and acute-to-short-term MAA on brain
      metabolites. METHODS: Adults with chronic MA dependence (n = 31) and healthy
      controls (n = 22) were recruited. Two-dimensional chemical shift 1H-MRS imaging
      (TR2000 ms, TE30 ms) slice was performed and included voxels in bilateral
      anterior-cingulate (ACC), frontal-white-matter (FWM), and dorsolateral-prefrontal
      cortices (DLPFC). Control participants were scanned once. The MA group was
      scanned twice, with acute (1.5 +/- 0.6 weeks, n = 31) and short-term MAA (5.1 +/-
      0.8 weeks, n = 22). The change in 1H-MRS metabolites over time (n = 19) was also
      investigated. Standard 1H-MRS metabolites are reported relative to Cr + PCr.
      RESULTS: Acute MAA showed lower n-acetyl-aspartate (NAA) and n-acetyl-aspartate
      with n-acetyl-aspartyl-glutamate (NAA + NAAG) in left DLPFC, and
      glycerophosphocholine with phosphocholine (GPC + PCh) in left FWM. Short-term MAA
      showed lower NAA + NAAG and higher myo-inositol (mI) in right ACC, lower NAA and
      NAA + NAAG in the left DLPFC, and lower GPC + PCh in left FWM. Over time, MAA
      showed decreased NAA and NAA + NAAG and increased mI in right ACC, decreased NAA
      and NAA + NAAG in right FWM, and decreased in mI in left FWM. CONCLUSION: In
      acute MAA, there was damage to the integrity of neuronal tissue, which was
      enhanced with short-term MAA. From acute to short-term MAA, activation of
      neuroinflammatory processes are suggested. This is the first 1H-MRS study to
      report the development of neuroinflammation with loss of neuronal integrity in
      MAA.

PMID- 29471228
TI  - Correlates and trends in youth co-use of marijuana and tobacco in the United
      States, 2005-2014.
AB  - BACKGROUND: Past-month marijuana and tobacco use (co-use) are increasing among
      U.S. adults, but little is known about the prevalence of co-use among U.S. youth.
      This study uses nationally representative data to assess the prevalence,
      correlates, and trends in co-use of marijuana and tobacco, tobacco-only use, and
      marijuana-only use among U.S. youth. METHODS: Data came from 176,245 youth ages
      12-17 who responded to the National Survey on Drug Use and Health - a nationally
      representative, household interview survey - between 2005 and 2014. Prevalence,
      demographics and substance use characteristics from 2013 to 14 were assessed
      across three groups: past-month users of marijuana and tobacco (co-users), past
      month tobacco-only users, and past-month marijuana-only users. Multinomial
      logistic regression was used to assess demographic correlates of each group.
      Linear and quadratic trends were assessed from 2005 to 2014 using logistic
      regression with orthogonal polynomials. RESULTS: In 2013-14, 5.4% of youth
      reported past-month co-use of tobacco and marijuana, 2.2% reported marijuana-only
      use, and 3.9% reported tobacco-only use. Co-use was associated with higher
      prevalence of past year marijuana dependence (vs. marijuana-only users), and
      higher past-month risky alcohol and other illicit drug use (vs. both tobacco and
      marijuana-only use groups). Co-use did not increase significantly between 2005
      and 2014; tobacco-only use declined, and marijuana-only use increased.
      CONCLUSIONS: Co-use of marijuana and tobacco is more prevalent than tobacco-only
      or marijuana-only use in U.S. youth. Given changing tobacco and marijuana
      policies, ongoing surveillance and studies that seek to increase our
      understanding of co-use behaviors in youth are critical.

PMID- 29471229
TI  - Impacts of biochar on the environmental risk of antibiotic resistance genes and
      mobile genetic elements during anaerobic digestion of cattle farm wastewater.
AB  - Biochar has positive effects on nitrogen conservation during anaerobic digestion,
      but its impacts on antibiotic resistance genes (ARGs) are unclear. Therefore, the
      effect of biochar (0, 5, 20, and 50 g/L) on the environmental risk of ARGs during
      cattle manure wastewater anaerobic digestion were investigated. The results
      showed that 5 g/L biochar reduced the relative abundances (RAs) of 5/13 ARGs
      while 20 g/L biochar significantly reduced the total RAs of ARGs in the digestion
      products, where the RA of ISCR1 was 0.89 log lower than the control. Biochar
      mainly affected the distribution of ARGs by influencing the RAs of Firmicutes and
      Proteobacteria, and the influence of 20 g/L biochar was greater than that of 5
      g/L. Mobile genetic elements also influenced the ARG profiles, especially intI2
      and ISCR1. The addition of 20 g/L biochar to cattle farm wastewater anaerobic
      digestion systems could reduce the environmental risk of ARGs.

PMID- 29471230
TI  - Variations of floc morphology and extracellular organic matters (EOM) in relation
      to floc filterability under algae flocculation harvesting using polymeric
      titanium coagulants (PTCs).
AB  - The work evaluated the algae cells removal efficiency using titanium salt
      coagulants with different degree of polymerization (PTCs), and the algae cells
      aggregates and extracellular organic matter (EOM) under chemical flocculation
      were investigated. The results indicated that PTCs performed well in algae cells
      flocculation and separation. The main mechanism using PTCs of low alkalisation
      degree for algae flocculation was associated with charge neutralization, while
      adsorption bridging and sweep flocculation was mainly responsible for algae
      removal by PTCs of high alkalisation degree treatment. In addition, the flocs
      formed by PTC1.0 showed the best filtration property, and EOM reached the minimum
      at this time, indicating the flocs formed by PTC1.0 were more compact than other
      PTCs, which can be confirmed by SEM analysis. Three-dimensional excitation
      emission matrix fluorescence (3D-EEM) and high performance size exclusion
      chromatography (HPSEC) revealed that the EOMs were removed under PTCs
      flocculation, which improved floc filterability.

PMID- 29471231
TI  - A novel methanotrophic co-metabolic system with high soluble methane
      monooxygenase activity to biodegrade refractory organics in pulping wastewater.
AB  - Pulping wastewater still contains massive refractory organics after biotreatment,
      with high colority, low biodegradability, and lasting biotoxicity. To eliminate
      refractory organics in pulping wastewater, a methanotrophic co-metabolic system
      in a gas cycle Sequencing Batch Biofilm Reactor (gcSBBR) seeded by soil at a
      ventilation opening of coal mine was quickly built on the 92nd day. The removal
      rate of COD, colority and TOC was 53.28%, 50.59% and 51.60%, respectively.
      Analysis of 3D-EEM indicated that glycolated protein-like, melanoidin-like or
      lignocellulose-like, and humic acid-like decreased by 7.85%, 5.02% and 1.74%,
      respectively. Moreover, this system exhibited high activity of soluble methane
      monooxygenase (sMMO) and mmoX encoding sMMO reached up to 7.89 * 105 copies/MUL.
      Methanotrophs, namely, Methylocaldum (8.28%), Methylococcus (6.06%) and
      Methylomonas (0.07%), were detected by 16S rRNA sequencing. And other bacteria
      were dominated by Denitratisoma, Anaerolineaceae_uncultured and
      Methylophilaceae_uncultured. Refractory organics was biodegraded through the
      synergy among microorganisms, and a postulated synergy pathway was put forward.

PMID- 29471232
TI  - Changes in pro-inflammatory cytokine levels and late-life depression: A two year
      population based longitudinal study.
AB  - Longitudinal associations of cytokine levels with depression are unclear. This
      study aimed to investigate cross-sectional and prospective associations between
      five serum pro-inflammatory cytokine levels and late-life depression. 732 Korean
      people aged 65+ were evaluated at baseline. Of 631 without depression (Geriatric
      Mental State schedule) at baseline, 521 (83%) were followed over a 2 year period
      and incident depression was ascertained. Serum tumor necrosis factor-alpha,
      interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-8 levels were assayed at both
      baseline and follow-up. Associations between cytokine levels and depressive
      status were evaluated using linear regression models, considering potential
      covariates (demographics, cognitive function, disability, lifestyle factors, and
      vascular risk factors) and applying Bonferroni corrections. Prevalent depression
      at baseline was significantly associated with higher contemporaneous levels of IL
      1beta and IL-8, independent of relevant covariates and after applying Bonferroni
      corrections. In the analyses of the five cytokine levels in combination,
      independent associations were found between prevalent depression and increased
      numbers of cytokines at higher levels at baseline. Incident depression was
      significantly associated with increases in IL-1beta, IL-6, and IL-8 levels during
      the follow-up independent of relevant covariates and after applying Bonferroni
      corrections. In combination analyses, incident depression was independently
      associated with higher numbers of cytokines showing increasing levels over the
      same follow-up period. However, incident depression was not predicted by higher
      baseline pro-inflammatory cytokine levels in any analysis. Our findings suggest
      that depression might affect serum cytokines alterations and lead to inflammatory
      processes in late-life.

PMID- 29471233
TI  - A Raman spectroscopy study on the effects of intermolecular hydrogen bonding on
      water molecules absorbed by borosilicate glass surface.
AB  - The structural forms of water/deuterated water molecules located on the surface
      of borosilicate capillaries have been first investigated in this study on the
      basis of the Raman spectral data obtained at different temperatures and under
      atmospheric pressure for molecules in bulk and also for molecules absorbed by
      borosilicate glass surface. The strongest two fundamental bands locating at
      3063cm-1 (2438cm-1) in the recorded Raman spectra are assigned here to the OH
      (OD) bond stretching vibrations and they are compared with the corresponding
      bands observed at 3124cm-1 (2325cm-1) in the Raman spectrum of ice Ih. Our
      spectroscopic observations have indicated that the structure of water and
      deuterated water molecules on borosilicate surface is similar to that of ice Ih
      (hexagonal phase of ice). These observations have also indicated that water
      molecules locate on the borosilicate surface so as to construct a bilayer
      structure and that strong and weak intermolecular hydrogen bonds are formed
      between water/deuterated molecules and silanol groups on borosilicate surface. In
      accordance with these findings, water and deuterated water molecules at the
      interface of capillary have a higher melting temperature.

PMID- 29471234
TI  - Influences of motorcycle rider and driver characteristics and road environment on
      red light running behavior at signalized intersections.
AB  - In Thailand, red light running is considered as one of the most dangerous
      behaviors at intersection. Red light running (RLR) behavior is the failure to
      obey the traffic control signal. However, motorcycle riders and car drivers who
      are running through red lights could be influenced by human factors or road
      environment at intersection. RLR could be advertent or inadvertent behavior
      influenced by many factors. Little research study has been done to evaluate the
      contributing factors influencing the red-light violation behavior. This study
      aims to determine the factors influencing the red light running behavior
      including human characteristics, physical condition of intersection, traffic
      signal operation, and traffic condition. A total of 92 intersections were
      observed in Chiang Mai, Nakhon Ratchasima, and Chonburi, the major provinces in
      each region of Thailand. In addition, the socio-economic characteristics of red
      light runners were obtained from self-reported questionnaire survey. The Binary
      Logistic Regression and the Multiple Linear Regression models were used to
      determine the characteristics of red light runners and the factors influencing
      rates of red light running respectively. The results from this study can help to
      understand the characteristics of red light runners and factors affecting them to
      run red lights. For motorcycle riders and car drivers, age, gender, occupation,
      driving license, helmet/seatbelt use, and the probability to be penalized when
      running the red light significantly affect RLR behavior. In addition, the results
      indicated that vehicle travelling direction, time of day, existence of turning
      lane, number of lanes, lane width, intersection sight distance, type of traffic
      signal pole, type of traffic signal operation, length of yellow time interval,
      approaching speed, distance from intersection warning sign to stop line, and
      pavement roughness significantly affect RLR rates.

PMID- 29471235
TI  - Competition between heavy metal ions for binding sites in lichens: Implications
      for biomonitoring studies.
AB  - The competitive behavior of divalent heavy metals (Cd, Cr, Pb, Zn) during cation
      uptake was investigated in the foliose lichen Xanthoria parietina. Lichen thalli
      were incubated with solutions containing 10 and 100 MUM of CdCl2, CuCl2, and
      ZnCl2 as well as 5 and 50 MUM of Pb(NO3)2, tested individually and in combination
      (Cd2++Cu2++Pb2++Zn2+). The analysis of molar concentrations suggests that a
      competition between cations for binding sites in X. parietina does exist. The
      decrease in net uptake between single and mixed solutions ranged between 14 and
      29% at the lowest concentration and between 38 and 68% at the highest
      concentration. Furthermore, the uptake was proportionally lower for richer
      solutions. Each metal may behave differently when uptook: some (toxic elements)
      are preferentially stored at extracellular level (Cd, Pb), while others (micro
      nutrients) are also present at intracellular level (Cu and Zn). The proportion
      between extracellular and total content changed for those elements accumulated
      also at intracellular level (Cu and Zn), while for Cd and Pb almost all the
      uptake occurred by passive mechanisms mainly at extracellular binding sites. The
      competition between metals for binding sites in the lichen surface entails that
      bioaccumulation data might result in an underestimation of some element levels
      measured in biomonitoring studies.

PMID- 29471236
TI  - Shifts of system performance and microbial community structure in a constructed
      wetland after exposing silver nanoparticles.
AB  - The increasing utilization of silver nanoparticles (Ag NPs) in industry and
      commerce inevitably raises its release into wastewater. In this work, effects of
      Ag NPs on system performance and microbial community along the way of a vertical
      flow constructed wetland (VFCW) were investigated, along with the removal and
      fate of Ag NPs within the system. Results showed that the performance of control
      wetland kept stable during the experimental period, and the top substrate layer
      (soil layer) of wetland could remove most of pollutants in the influent. The
      study also suggested that addition of Ag NPs did not significantly affect organic
      matters removal. However, adverse effects were observed on the nitrogen and
      phosphorus removal. Removal efficiencies of TN, NH4+-N and TP approximately
      obviously reduced by approximately 10.10%, 8.42% and 28.35% respectively in
      contrast to before dosing after exposing 100 MUg/L Ag NPs for 94 d, while the no
      dosing wetland with the stable performance. It was found that Ag NPs accumulated
      in the upper soil layer more than in the lower soil layer, and Ag NPs could enter
      into the plant tissues. After continuous input of Ag NPs, removal efficiency of
      Ag NPs was measured as 95.72%, which showed that the CW could effectively remove
      Ag NPs from the wastewater. The high-throughput sequencing results revealed that
      Ag NPs caused the shifts in microbial community structures and changed the
      relative abundances of key functional bacteria, which finally resulted in a lower
      efficiency of biological nitrogen and phosphorus removal.

PMID- 29471237
TI  - Quantifying the harmful potential of ten essential oils on immature Trichogramma
      pretiosum stages.
AB  - The use of chemical insecticides and non-selective natural products authorized
      for use in organic farming may reduce the effectiveness of egg parasitoids. The
      side-effects of ten plant essential oils on immature stages of Trichogramma
      pretiosum were evaluated. Carapa guianensis, Origanum vulgare and Zingiber
      officinalle during the F1 generation, and Azadirachtin and Mentha piperita in the
      F2 generation were slightly harmful (class II: 30-79%) to the emergence of this
      parasitoid. All essential oils affected the longevity of females of the F1 and F2
      generations. Thymus vulgaris and Z. officinalle were the oils most harmful to
      female longevity. Carapa guianensis proved slightly harmful (class II: 30-79%) to
      parasitism in the F1 generation when applied during the egg-larval and pre-pupal
      stages and O. vulgare in the F1 generation in the pre-pupal stage alone, of this
      parasitoid. The sex ratio was lower than 0.5 during the pre-pupal stage of the F1
      generation with Azadirachtin, C. guianensis, O. vulgare, Piper nigrum and
      Syzigium aromaticum, but this parameter was not affected for the other biological
      stages of T. pretiosum in the F1 and F2 generations. The Azadirachtin, C.
      guianensis, M. piperita, O. vulgare, T. vulgaris and Z. officinalle oils revealed
      a mild toxic effect to the immature stages of T. pretiosum and, therefore, it
      should be used according to patterns of ecological selectivity. Allium sativum
      and Citrus sinensis essential oils were not harmful to T. pretiosum, and can be
      used in Integrated Pest Management.

PMID- 29471238
TI  - Prediction of soil urea conversion and quantification of the importance degrees
      of influencing factors through a new combinatorial model based on cluster method
      and artificial neural network.
AB  - Quantitative prediction of soil urea conversion is crucial in determining the
      mechanism of nitrogen transformation and understanding the dynamics of soil
      nutrients. This study aimed to establish a combinatorial prediction model (MCA-F
      ANN) for soil urea conversion and quantify the relative importance degrees (RIDs)
      of influencing factors with the MCA-F-ANN method. Data samples were obtained from
      laboratory culture experiments, and soil nitrogen content and physicochemical
      properties were measured every other day. Results showed that when MCA-F-ANN was
      used, the mean-absolute-percent error values of NH4+-N, NO3--N, and NH3 contents
      were 3.180%, 2.756%, and 3.656%, respectively. MCA-F-ANN predicted urea
      transformation under multi-factor coupling conditions more accurately than
      traditional models did. The RIDs of reaction time (RT), electrical conductivity
      (EC), temperature (T), pH, nitrogen application rate (F), and moisture content
      (W) were 32.2%-36.5%, 24.0%-28.9%, 12.8%-15.2%, 9.8%-12.5%, 7.8%-11.0%, and 3.5%
      6.0%, respectively. The RIDs of the influencing factors in a descending order
      showed the pattern RT > EC > T > pH > F > W. RT and EC were the key factors in
      the urea conversion process. The prediction accuracy of urea transformation
      process was improved, and the RIDs of the influencing factors were quantified.

PMID- 29471239
TI  - Identification of miR-200c-3p as a major regulator of SaoS2 cells activation
      induced by fluoride.
AB  - The skeletal lesion of fluoride has become a major concern in many countries due
      to its damage to bone and joints and even leading to disability. Skeletal
      fluorosis is characterized by disturbance of bone metabolism, aberrant
      proliferation and activation of osteoblasts is critical for the pathogenesis.
      However, the mechanism underlying the osteotoxicity of fluoride has not been
      clearly illustrated and there is still limited information on the role of miRNAs
      in skeletal fluorosis. In this study, we found that NaF promoted SaoS2
      proliferation and activation by activating BMP4/Smad pathway. NaF increased
      expression of miR-200c-3p and miR-200c-3p inhibitor reduced activation of SaoS2
      induced by NaF via targeting Noggin to repress BMP4/Smad. These findings
      suggested an important regulatory role of miR-200c-3p on BMP4/Smad pathway during
      skeletal fluorosis. MiR-200c-3p might be a novel therapeutic target for skeletal
      fluorosis.

PMID- 29471240
TI  - A multiregional survey of nickel in outdoor air particulate matter in China:
      Implication for human exposure.
AB  - Nickel is a widespread environmental contaminant, and it is toxic to humans in
      certain forms at high doses. Despite this, nationwide data on nickel in outdoor
      air particulate matter and human exposure to nickel through inhalation in China
      are limited. In the present study, 662 outdoor air samples from seven
      representative provinces such as Shanghai, Hubei, Hunan, Hebei, Guangdong,
      Yunnan, and Shanxi were collected between March 2013 and February 2014 and
      analyzed by inductively coupled plasma mass spectrometry. The concentrations of
      nickel in the air were in the range of 2.1-80.9 ng/m3 (geometric mean: 14.4
      ng/m3). In most areas, the concentrations of nickel were higher in winter and
      spring than those measured in summer and autumn. The daily intake (median) of
      nickel through inhalation of air particulate matter was estimated. Although the
      nickel concentrations in some air samples were high, inhalation of the air
      particulate matter accounted for a minor part of the total nickel intake;
      however, the adverse effects of human exposure to nickel through inhalation and
      its potential sources require more attention, particularly in Shanghai. This is a
      multiregional survey of nickel in outdoor air particulate matter in China.

PMID- 29471241
TI  - Influence of chelation on the Fenton-based electrochemical degradation of
      herbicide tebuthiuron.
AB  - This study describes the performance of electro-Fenton (EF) and photoelectro
      Fenton (PEF) processes to degrade the herbicide tebuthiuron (TBH) in 0.050 M
      Na2SO4 at pH = 3.0. Experiments were performed in an undivided cell equipped with
      a boron-doped diamond (BDD) or Pt anode and an air-diffusion cathode that
      produces H2O2. Physisorbed hydroxyl radicals (M(OH)) generated from water
      oxidation at the anode and/or free OH formed from Fenton's reaction acted as main
      oxidants. All processes became much more effective using a BDD anode because of
      the higher oxidation power of BDD(OH). Sulfate and nitrate were the predominant
      ions released during TBH destruction. In both, EF and PEF treatments, two
      distinct kinetic regimes were observed, the first one corresponding to the
      oxidation of free TBH by OH and the second one to that of the Fe(III)-TBH complex
      by M(OH). The effect of Fe2+ and TBH concentrations on the kinetics of both
      regions has been examined. Moreover, a poor mineralization was reached with Pt
      anode, whereas almost total mineralization was attained by EF and PEF with BDD.
      Both processes showed analogous mineralization rates because the intermediates
      produced could not be photodegraded by UVA light. Gas chromatography-mass
      spectrometry analysis of electrolyzed solutions revealed the generation of eight
      heteroaromatics along with 1,3-dimethylurea, which have been included in a
      reaction pathway proposed for the initial degradation of TBH.

PMID- 29471242
TI  - Development of a glucose sensor employing quick and easy modification method with
      mediator for altering electron acceptor preference.
AB  - Enzyme based electrochemical biosensors are divided into three generations
      according to their type of electron transfer from the cofactors of the enzymes to
      the electrodes. Although the 3rd generation sensors using direct electron
      transfer (DET) type enzymes are ideal, the number of enzyme types which possess
      DET ability is limited. In this study, we report of a glucose sensor using
      mediator-modified glucose dehydrogenase (GDH), that was fabricated by a new quick
      and-easy method using the pre-functionalized amine reactive phenazine ethosulfate
      (arPES). Thus mediator-modified GDH obtained the ability to transfer electrons to
      bulky electron acceptors as well as electrodes. The concentration of glucose was
      successfully measured using electrodes with immobilized PES-modified GDH, without
      addition of external electron mediators. Therefore, continuous monitoring systems
      can be developed based on this "2.5th generation" electron transfer principle
      utilizing quasi-DET. Furthermore, we successfully modified two other
      diagnostically relevant enzymes, glucoside 3-dehydrogenase and lactate oxidase,
      with PES. Therefore, various kinds of diagnostic enzymes can achieve quasi-DET
      ability simply by modification with arPES, suggesting that continuous monitoring
      systems based on the 2.5th generation principle can be developed for various
      target molecules.

PMID- 29471243
TI  - TRPS1 Suppresses Breast Cancer Epithelial-mesenchymal Transition Program as a
      Negative Regulator of SUZ12.
AB  - Breast cancer (BC) is among the most common malignant diseases and metastasis is
      the handcuff of treatment. Cancer metastasis is a multistep process associated
      with the epithelial-mesenchymal transition (EMT) program. Several studies have
      demonstrated that transcriptional repressor GATA binding 1 (TRPS1) played
      important roles in development and progression of primary BC. In this study we
      sought to identify the mechanisms responsible for this function of TRPS1 in the
      continuum of the metastatic cascade. Here we described that TRPS1 was
      significantly associated with BC metastasis using public assessable datasets.
      Clinically, loss of TRPS1 expression in BC was related to higher histological
      grade. In vitro functional study and bioinformatics analysis revealed that TRPS1
      inhibited cell migration and EMT in BC. Importantly, we identified SUZ12 as a
      novel target of TRPS1 related to EMT program. ChIP assay demonstrated TRPS1
      directly inhibited SUZ12 transcription by binding to the SUZ12 promoter. Loss of
      TRPS1 resulted in increased SUZ12 binding and H3K27 tri-methylation at the CDH1
      promoter and repression of E-cadherin. In all, our data indicated that TRPS1
      maintained the expression of E-cadherin by inhibiting SUZ12, which might provide
      novel insight into how loss of TRPS1 contributed to BC progression.

PMID- 29471244
TI  - Two sesquiterpene aminoquinones protect against oxidative injury in HaCaT
      keratinocytes via activation of AMPKalpha/ERK-Nrf2/ARE/HO-1 signaling.
AB  - AIMS: To investigate the cytoprotective effects of two sesquiterpene
      aminoquinones isolated from the marine sponge Dysidea fragilis, Dysidaminone H
      (DA8) and 3'-methylamino-avarone (DA14), we examined their effects against
      hydrogen peroxide (H2O2)-induced oxidative injury in human keratinocyte cell line
      and elucidated the underlying mechanisms. MAIN METHODS: Cell viability was
      detected using a CCK-8 assay kit. Intracellular reactive oxygen species (ROS)
      production was measured by fluorescence of 2, 7-Dichlorodi-hydrofluorescein
      diacetate (DCFH-DA). Messenger RNA and protein expression were measured by real
      time quantitative PCR and western blotting analysis. Immunocytochemistry was
      performed to determine the intracellular location of nuclear factorerythroid 2
      p45 related factor 2 (Nrf2). The antioxidant response element (ARE)-luciferase
      reporter gene assay and RNA interference were used to establish the role of ARE
      and Nrf2. KEY FINDINGS: DA8 and DA14 (DAs) resisted H2O2induced decline of cell
      viability by inhibiting the accumulation of ROS. Meanwhile, DAs increased HO-1
      expression and ARE activity and induced Nrf2 expression, as well as the
      accumulation of Nrf2 in the cell nucleus. However, silencing of Nrf2 abolished
      DAs-induced HO-1 expression and ARE luciferase activation. In addition, DAs
      induced the phosphorylation of both cyclic AMP-activated protein kinase-alpha
      (AMPKalpha) and extracellular signal-regulated kinase (ERK), while specific
      inhibitors of AMPKalpha and ERK abrogated HO1 upregulation and Nrf2 activation.
      SIGNIFICANCE: DAs provided cytoprotective effects against H2O2-induced
      cytotoxicity by activation of the Nrf2/ARE/HO-1 pathway via phosphorylation of
      AMPKalpha and ERK. The findings suggested that DA8 and DA14 might be the
      candidate therapeutic agents for skin diseases caused by oxidative injury.

PMID- 29471245
TI  - Intraperitoneal administration of mesenchymal stem cells ameliorates acute
      dextran sulfate sodium-induced colitis by suppressing dendritic cells.
AB  - Dendritic cells (DCs) have important pathogenic role in the induction and
      progression of ulcerative colitis (UC), but their role in mesenchymal stem cells
      (MSCs)-mediated suppression of colon injury and inflammation is not revealed. By
      using dextran sodium sulfate (DSS)-induced colitis, a well-established murine
      model of UC, we examined effects of MSCs on phenotype and function of colon
      infiltrating DCs. Clinical, histological, immunophenotypic analysis and passive
      transfer of MSCs-primed DCs were used to evaluate capacity of MSC to suppress
      inflammatory phenotype of DCs in vivo. Additionally, DCs:MSCs interplay was also
      investigated in vitro, to confirmed in vivo obtained findings. Intraperitoneally
      administered MSCs (2 * 106) significantly reduced progression of DSS-induced
      colitis and reduced serum levels of inflammatory cytokines (IL-1beta, IL-12, and
      IL-6). Passive transfer of in vivo MSCs-primed DCs reduced severity of colitis
      while passive transfer of MSCs-non-primed DCs aggravated DSS-induced colitis.
      Through the secretion of immunomodulatory Galectin 3, MSCs, in paracrine manner,
      down-regulated production of inflammatory cytokines in DCs and attenuated
      expression of co-stimulatory and major histocompatibility complex class II
      molecules on their membranes. Taken together, these results indicate that MSCs
      achieved their beneficial effects in DSS-induced colitis by suppressing
      inflammatory phenotype of DCs in Gal-3 dependent manner. Therapeutic targeting of
      DCs by MSCs should be explored in future studies as a useful approach for the
      treatment of UC.

PMID- 29471246
TI  - Effects of sunitinib targeted chemotherapy on the osseointegration of titanium
      implants.
AB  - Targeted chemotherapies are novel therapeutic approaches for many malignancies.
      In contrast to conventional chemotherapies, which are given for a predetermined
      duration, treatment with targeted chemotherapies like sunitinib is routinely
      continuous over longer periods, sometimes years. During this prolonged treatment
      period, patients may need to restore their missing teeth with dental implants.
      The aim of this study was to examine the effect of the anti-angiogenic substance
      sunitinib targeted chemotherapy on the osseointegration of titanium implants in a
      rabbit model. Fourteen white New Zealand rabbits were randomly assigned to two
      groups of either oral sunitinib at 10 mg/kg twice per week dose for 4 weeks (n =
      7) or placebo (n = 7). The first dose was given 2 days before the surgical
      intervention. Each rabbit received one titanium dental implant in the right
      distal femoral condyle. Four weeks following implant insertion, rabbits were
      sacrificed and bone specimens containing the implants were retrieved.
      Osseointegration of the implants was analyzed using micro-computed tomography and
      histomorphometric evaluation. Both micro-computed tomography and
      histomorphometric analysis showed that the osseointegration parameters, including
      the ratio of bone volume to total volume and bone-implant contact percent for the
      sunitinib group were significantly lower than those in the control group (P <=
      0.05). Sunitinib targeted chemotherapy had a negative effect on the
      osseointegration of titanium implants inserted in a rabbit model.

PMID- 29471247
TI  - Family functioning and adolescent internalizing symptoms: A latent profile
      analysis.
AB  - This study aimed to characterize adolescent family functioning typologies using
      latent profile analysis (LPA). A secondary aim was to examine profile
      associations with adolescent internalizing symptoms at one-year follow-up.
      Students (N = 1029; 53% female; mean age = 16.14, SD = .75 years) completed
      measures of family functioning, anxiety, and depressive symptoms at two time
      points. LPA was conducted to characterize family functioning typologies at Time
      1, revealing five profiles: 1) Low Family Functioning, 2) Only Close to Father,
      3) Average Family Functioning, 4) Only Close to Mother, and 5) High Family
      Functioning. Results indicated that the Low and Only Close to Mother profiles had
      greater depressive symptoms at Time 2, compared with the Average profile. The
      High profile had fewer depressive symptoms at Time 2. The Low and Only Close to
      Mother profiles also had significantly more anxiety symptoms at Time 2. Findings
      highlight the utility of examining family functioning profiles.

PMID- 29471248
TI  - Using structured light three-dimensional surface scanning on living individuals:
      Key considerations and best practice for forensic medicine.
AB  - Non-contact three-dimensional (3D) surface scanning methods have been applied to
      forensic medicine to record injuries and to mitigate ordinary photography
      shortcoming. However, there are no literature concerning practical guidance for
      3D surface scanning of live victims. This paper aimed to investigate key 3D
      scanning issues of the live body to develop a series of scanning principles for
      future use on injured victims. The Pico Scan 3D surface scanner was used on live
      test subjects. The work focused on analysing the following concerns: (1) an
      appropriate 3D scanning technique to scan different body areas, (2) the ideal
      number of scans, (3) scanning approaches to access various areas of the body and
      (4) elimination of environmental background noise in the acquired data. Results
      showed that scanning only a required surface of the body area in the stable
      manner was more efficient when compared to complete 360 degrees -scanning;
      therefore, it used as a standard 3D scanning technique. More than three scans
      were sufficient when trying to obtain an optimal wireframe mode presentation of
      the result. Three different approaches were suggested to provide access to the
      various areas of the body. Undertaking scanning using a black background
      eliminated the background noise. The work demonstrated that the scanner will be
      promising to reconstruct injuries from different body areas, although the 3D
      scanning of the live subjects faced some challenges.

PMID- 29471249
TI  - Post-mortem biochemistry of NSE and S100B: A supplemental tool for detecting a
      lethal traumatic brain injury?
AB  - PURPOSE: Traumatic brain injury (TBI) is a very common entity that leads to
      numerous fatalities all over the world. Therefore, forensic pathologists are in
      desperate need of supplemental methodological tools for the diagnosis of TBI in
      everyday practice besides the standard autopsy. The present study determined post
      mortem neuron specific enolase (NSE) and S100 calcium-binding protein B (S100B)
      levels as biological markers of an underlying TBI in autopsy cases. METHODS:
      Paired serum and CSF samples of 92 fatalities were collected throughout routine
      autopsies. Afterwards, the marker levels were assessed using commercially
      available immunoassays (ECLIA, Roche Diagnostics). For statistical analysis, we
      compared the TBI cases to three control groups (sudden natural death by acute
      myocardial infarction, traumatic death without impact on the head, cerebral
      hypoxia). Moreover, the TBI cases were subdivided according to their survival
      time of the trauma. Brain specimens have been collected and stained
      immunohistochemically against the aforementioned proteins to illustrate their
      typical cellular staining patterns with an underlying TBI compared to non-TBI
      fatalities. PRINCIPAL RESULTS: CSF NSE and S100B levels were elevated after TBI
      compared to all control groups (p < 0.001). Although this finding can already be
      investigated among the TBI cases dying immediately subsequent to the trauma, the
      marker levels in CSF increase with longer survival times until a peak level
      within the first three days after trauma. There is a strong correlation between
      both marker levels in CSF (r = 0.67). The presence or absence of cerebral tissue
      contusion following the initial trauma does not seem to affect the CSF levels of
      both proteins (p > 0.05). Post-mortem serum levels of both proteins were not
      elevated in TBI cases compared to controls (p > 0.05). Former elaborated cut-off
      values in CSF were confirmed and were only exceeded when a TBI survival time of
      at least 30 min was reached. MAJOR CONCLUSIONS: The present results report that
      post-mortem NSE and S100B CSF levels are significantly elevated subsequent to a
      fatal TBI.

PMID- 29471250
TI  - Duret haemorrhage: An unusual finding in compression of neck structures.
AB  - Hanging is one of the most lethal methods of suicide, where survival is an
      obvious rarity. Those who survive the initial act of hanging mostly suffer from
      hypoxic ischemic encephalopathy, and show some form of neurological damage.
      Intracranial haemorrhages are rarely associated with hanging. We report the first
      case of Duret haemorrhages in a 58 years old victim who survived for 8 days after
      the attempted hanging. Duret haemorrhage is mostly associated with fatal outcome.
      It is thus implied that cerebral edema should be brought under control at the
      earliest to prevent transtentorial herniation and subsequent Duret haemorrhages.

PMID- 29471251
TI  - Adopting data interpretation on mining fine-grained near-repeat patterns in
      crimes.
AB  - The near-repeat effect is a well-known phenomenon in crime analysis. The classic
      research methods focus on two aspects. One is the geographical factor, which
      indicates the influence of a certain crime risk on other similar crime incidents
      in nearby places. The other is the social network, which demonstrates the
      contacts of the offenders and explain "near" as degrees instead of geographic
      distances. In our work, these coarse-grained patterns discovering methods are
      summarized as bundled-clues techniques. In this paper, we propose a knotted-clues
      method. Adopting a data science perspective, we make use of a data interpretative
      technology and discover that the near-repeat effect is not always so near in
      geographic or network structure. With this approach, we analyze the near-repeat
      patterns in all districts of the dataset, as well as in different crime types.
      Using open source data from Crimes in Chicago provided by Chicago Police
      Department, we find interesting relationships and patterns with our mining
      method, which have a positive effect on police deployment and decision making.

PMID- 29471252
TI  - Relationship between monocytes to lymphocytes ratio and axial spondyloarthritis.
AB  - BACKGROUND: Axial spondyloarthritis (axSpA) is a progressive, chronic,
      inflammatory skeletal disorder affecting the spine and sacroiliac joints. Many
      studies have shown that neutrophils, lymphocytes, monocytes, platelets, and red
      blood cells (RBCs) play important roles in the inflammatory process of axSpA.
      Neutrophils to lymphocytes ratio (NLR) and red blood cell distribution width
      (RDW) have been reported to be simple and inexpensive markers to indicate the
      disease activity of axSpA. However, the role of monocytes to lymphocytes ratio
      (MLR) and platelets to lymphocytes ratio (PLR) in axSpA was rarely mentioned.
      OBJECTIVE: The study's aim was to determine the role of MLR and PLR in axSpA
      patients and to investigate their relationships with disease severity. METHODS:
      AxSpA patients who fulfilled the Assessment in Ankylosing Spondylitis
      International Society classification criteria published in 2009 were enrolled in
      this study and divided into nonradiographic axial spondyloarthritis (nr-axSpA)
      group and ankylosing spondylitis (AS) group. Healthy age and gender-matched
      subjects were also enrolled as control group. MLR, PLR, NLR, RDW, C-reactive
      protein (CRP) level, and erythrocyte sedimentation rate (ESR) level were
      assessed. The correlation between the variables with finger-to-floor distance,
      Modified Schober test, and occiput-to-wall distance were tested with Pearson
      correlation. Furthermore, area under curve (AUC) value, sensitivity, specificity,
      and the optimal cutoff values were determined using receiver operating
      characteristic (ROC) curves. RESULTS: A total of 148 axSpA patients (67 nr-axSpA
      patients and 81 AS patients) and 58 healthy subjects were included in the study.
      The MLR, NLR, PLR, and RDW in axSpA group were higher than those in the control
      group (P < 0.05). Among them, MLR and RDW were highly increased in AS group
      compared with the nr-axSpA group (P < 0.05). MLR, NLR, PLR, and RDW were all
      positively correlated with ESR level and CRP level (P < 0.05). MLR and RDW were
      positively correlated with finger-to-floor distance and negatively correlated
      with Modified Schober test (P < 0.05). RDW was positively correlated with occiput
      to-wall distance (P < 0.05). ROC curve results showed MLR yielded a higher AUC
      than NLR, PLR, and RDW (P < 0.05). In addition, the optimal cutoff value of MLR
      for axSpA was 0.22, with a specificity of 70.9% and sensitivity of 68.4%.
      CONCLUSIONS: MLR was elevated in AS patients compared to nr-axSpA patients and
      had a close relationship with CRP level, ESR level, and spine movements. MLR may
      be a reliable, cost-effective, and novel potential parameter to evaluate disease
      severity in axSpA.

PMID- 29471253
TI  - High performance resorbable composites for load-bearing bone fixation devices.
AB  - Bone fractures are some of the most common injuries annually, and many require a
      fixation device to help properly heal. The present study focuses on developing a
      bioresorbable composite that has high strength and stiffness for bone fixation
      applications. To achieve this, a design of experiments was performed, testing the
      effect of long fiber reinforcement type, matrix type, matrix amount, and particle
      reinforcement amount on the flexural properties of the composite. Based on these
      results, the ideal resorbable long fiber reinforcement, particle reinforcement,
      and matrix material are degummed silk fibroin, hydroxyapatite, and polylactic
      acid, respectively. Through further optimizations of the particle reinforcement
      phase a flexural modulus and strength of 13.7 GPa and 437 MPa, respectively, was
      achieved. Both values are among the highest found in literature, with the
      strength far exceeding the requirement for a fixation device and the highest for
      such a bioresorbable composite material, showing great promise for use as a
      bioresorbable fixation device.

PMID- 29471254
TI  - UPLC-MS/MS assay validation for tacrolimus quantitative determination in
      peripheral blood T CD4+ and B CD19+ lymphocytes.
AB  - Monitoring tacrolimus (Tac) exposure in cell matrices enriched with lymphocytes
      can improve Tac therapeutic drug monitoring (TDM) in solid organ transplant
      recipients. An UPLC-MS/MS based assay for Tac quantification in peripheral blood
      T CD4+ and B CD19+ lymphocytes was developed. Peripheral blood mononuclear cells
      (PBMC) were obtained by density gradient centrifugation and highly purified
      (purity >90%) T CD4+ and B CD19+ cell suspensions were acquired by magnetic
      negative selection from whole blood of 6 healthy volunteers. The purity of
      lymphocyte suspensions was checked by flow cytometry. Tac extraction was
      performed in a liquid-liquid zinc sulfate, methanol and acetonitrile based
      medium. Ascomycin was used as internal standard. The equipment used was a
      Waters(r) AcquityTM UPLC system (Waters Corporation, Milford, MA, USA). The
      chromatographic run was performed on a Waters(r) MassTrak TDM C18 (2.1 * 10 mm)
      column (Waters Corporation, Milford, MA, USA). at a flow rate of 0.4 mL/min. The
      instrument was set in electrospray positive ionization mode. The method was
      validated according to Clinical Laboratory Standard Institute (CLSI) guidelines
      and showed a high sensitivity and specificity over a range of 0-5.2 ng/mL in
      PBMC, 0-5.0 ng/mL in T CD4+ Lymphocytes and 0-5.3 ng/mL in B CD19+ lymphocytes.
      Precision was appropriate with CV of intra-assay quantifications ranging from 4.9
      to 7.4%, and of inter-assay quantifications from 7.2 to 13.9%. Limit of detection
      and quantification were 0.100 and 0.115 ng/mL in PBMC, 0.058 and 0.109 ng/mL in T
      CD4+ and 0.017 and 0.150 ng/mL in B CD19+ cells. Matrix effect was not
      significant among all the studied matrices. Samples showed stability for Tac
      quantification over a period of 90 days either at room temperature or at -30 
      degrees C storage conditions. The method was applied to clinical samples of 20
      kidney transplant recipients. Concentrations ranged from 2.200 to 11.900 ng/mL in
      whole blood, from 0.005 to 0.570 ng/106 cells in PBMC, from 0.081 to 1.432 ng/106
      cells in T CD4+, and from 0.197 to 1.564 ng/106 cells in B CD19+ cell matrices.
      The method has potential applicability for Tac TDM in solid organ transplant
      recipients.

PMID- 29471255
TI  - Non-stop aptasensor capable of rapidly monitoring norovirus in a sample.
AB  - A cost-effective and simple biosensor was developed for the accurate and rapid
      monitoring of norovirus GII in a sample. The modified DNA aptamer, 5 guanines
      linked to conventional DNA aptamer, designed for the research, was able to
      rapidly capture norovirus GII in tap water as well artificial urine. In addition,
      the extra guanines of the modified DNA aptamer enhanced the sensitivity of
      biosensor with guanine chemiluminescence detection based on the principle of
      intra chemiluminescent resonance transfer (Intra-CRET). This is because
      additional high-energy intermediates formed from the reaction of extra guanines
      and 3, 4, 5-trimethoxylphenylglyoxal (TMPG) were able to directly transfer energy
      to 6-carboxylfluorescein (6-FAM) to emit bright chemiluminescence. The biosensor
      operated without time-consuming and tedious procedures (e.g., sample
      pretreatment, long and multiple incubations, washings) was able to accurately
      quantify trace levels of norovirus GII capsid with excellent specificity and
      reproducibility. The limit of detection (LOD = 3sigma) of the biosensor for
      norovirus GII capsids in tap water was as low as 80 ng/ml. It is expected that
      the new technology confirmed while developing the biosensor can be applied to
      devise alternative biosensors capable of rapidly quantifying various food-borne
      pathogens in a sample.

PMID- 29471257
TI  - What is a practical duration time for capturing psychogenic non-epileptic
      seizures by video-EEG monitoring?

PMID- 29471256
TI  - Consensus research priorities for paediatric status epilepticus: A Delphi study
      of health consumers, researchers and clinicians.
AB  - PURPOSE: Status epilepticus (SE) is a paediatric emergency with significant
      morbidity and mortality. Recommendations beyond first line care are not based on
      high quality evidence. Emergency physicians and neurologists are key stakeholders
      in managing this condition. A collaborative, widely consulted approach to
      identifying priorities can help direct limited research funds appropriately. The
      objectives of this study are to identify consensus research priorities in
      paediatric SE among experts and health consumers. METHODS: A three-stage Delphi
      process was conducted. Paediatric Neurologists and Emergency Physicians in
      Australia and New Zealand participated. Round one asked participants to generate
      three research questions important for further research in paediatric status
      epilepticus. Responses were refined into unique individual questions. Rounds two
      and three required participants to rate questions on a seven point ordinal scale.
      Health consumers were invited to participate by providing up to three problem
      areas that could be addressed by research. RESULTS: 54 experts and 76 health
      consumers participated in the process. Nine questions reached our definition of
      consensus "high priority", 21 questions achieved consensus "low priority" and
      seven questions did not achieve consensus. High priority areas included second
      line management including levetiracetam (efficacy, dose and timing), use of third
      line agents, induction of anaesthesia (timing and best agent), management of
      focal SE, and indicators of "subtle SE". Consumer priority areas included themes
      of treatment efficacy, aetiology, and community education. CONCLUSION: We
      identified nine priority research questions in paediatric SE, congruent with the
      health consumer theme of treatment efficacy. Future research efforts should be
      directed towards these priority areas.

PMID- 29471258
TI  - Outcomes of pregnancies in women taking antiepileptic drugs for non-epilepsy
      indications.
AB  - PURPOSE: Antiepileptic drugs (AEDs), particularly valproate (VPA), are known to
      be teratogens when taken by women with epilepsy (WWE), but the risk in women who
      take these drugs for indications other than epilepsy have been little studied.
      This study aims to investigate the incidence of birth defects in children born to
      mothers taking AEDs for non-epilepsy indications. METHODS: The Australian
      Pregnancy Register (APR), established in 1998, is a prospective observational
      study operating with ethical approval and informed written consent for
      participation. Of the 2066 pregnancies enrolled in the Register, 98% are WWE and
      the remainder received AEDs for other indications. Data from this Register was
      analysed to study the rates of congenital malformations (CM) in infants exposed
      to AEDs in utero in WWE compared to those women taking AEDs for other
      indications. RESULTS: The malformation rates in pregnancies of WWE taking AEDs
      (5%), is higher than the rates of infants born to untreated WWE (2%). There were
      32 pregnancies enrolled from 29 mothers taking AEDs for indications other than
      epilepsy (2 women/2 pregnancies were lost to follow up). Out of 30 pregnancies, 9
      of which were exposed to VPA, 1 resulted in a child with a malformation (3%)
      (cleft palate) on 1700 mg/day of valproate. CONCLUSIONS: This is the first
      attempt to assess the use of AEDs in a prospective study of women who are
      pregnant but do not have active epilepsy. Although underpowered, this study
      suggests that women taking AEDs for non-epilepsy indications have a similar risk
      of having a child with a CM as compared with women taking AEDs for epilepsy.
      Larger numbers are required to investigate the risk of AED-associated
      malformations in this important group.

PMID- 29471259
TI  - Functional genomics and assays of regulatory activity detect mechanisms at loci
      for lipid traits and coronary artery disease.
AB  - Many genome-wide association studies (GWAS) have identified signals located in
      non-coding regions, and an increasing number of functional genomics annotations
      of regulatory elements and assays of regulatory activity have been used to
      investigate mechanisms. Genome-wide datasets that characterize chromatin
      structure help detect potential regulatory elements. Assays to experimentally
      assess candidate variants include transcriptional reporter assays, and recently,
      massively parallel reporter assays (MPRAs). Additionally, the effect of candidate
      regulatory elements and variants on gene expression and function can be evaluated
      using genomic editing with the CRISPR-Cas9 technology. We highlight some recent
      studies that employed these strategies to identify variant effects and elucidate
      molecular and/or biological mechanisms at GWAS loci for lipid traits and coronary
      artery disease.

PMID- 29471260
TI  - Stress underestimation and mental health literacy of depression in Japanese
      workers: A cross-sectional study.
AB  - Appropriately estimating stress levels in daily life is important for motivating
      people to undertake stress-management behaviors or seek out information on stress
      management and mental health. People who exhibit high stress underestimation
      might not be interested in information on mental health, and would therefore have
      less knowledge of it. We investigated the association between stress
      underestimation tendency and mental health literacy of depression (i.e.,
      knowledge of the recognition, prognosis, and usefulness of resources of
      depression) in Japanese workers. We cross-sectionally surveyed 3718 Japanese
      workers using a web-based questionnaire on stress underestimation, mental health
      literacy of depression (vignettes on people with depression), and covariates
      (age, education, depressive symptoms, income, and worksite size). After adjusting
      for covariates, high stress underestimation was associated with greater odds of
      not recognizing depression (i.e., choosing anything other than depression).
      Furthermore, these individuals had greater odds of expecting the case to improve
      without treatment and not selecting useful sources of support (e.g. talk over
      with friends/family, see a psychiatrist, take medication, see a counselor)
      compared to those with moderate stress underestimation. These relationships were
      all stronger among males than among females. Stress underestimation was related
      to poorer mental health literacy of depression.

PMID- 29471262
TI  - Generation of a human iPSC line, IISHDOi002-A, with a 46, XY/47, XYY mosaicism
      and belonging to an African mitochondrial haplogroup.
AB  - We have generated a human iPSC line, IISHDOi002-A, from commercial primary normal
      human dermal fibroblasts belonging to an African mitochondrial haplogroup (L3),
      and with a 46, XY/47, XYY mosaicism. For this purpose, reprogramming factors
      Oct3/4, Sox2, Klf4 and cMyc were delivered using a non-integrative methodology
      that involves the use of Sendai virus.

PMID- 29471261
TI  - Regulation of cortical and peripheral GCH1 expression and biopterin levels in
      schizophrenia-spectrum disorders.
AB  - Tetrahydrobiopterin (BH4) is an essential cofactor for dopamine, serotonin and
      nitric oxide synthesis. Deficits of plasma total biopterin (a measure of BH4)
      have been described in schizophrenia and schizoaffective disorder. GCH1 encodes
      the first and rate-limiting enzyme in BH4 synthesis. Peripheral GCH1 expression
      is lower in first episode psychosis patients versus controls, and we hypothesized
      that a GCH1 promoter polymorphism associated with psychiatric illness,
      contributes to regulation of both GCH1 expression and BH4 levels. We tested this
      hypothesis in 120 subjects (85 patients with schizophrenia or schizoaffective
      disorder and 35 controls): Patients with the rs10137071 A allele had
      significantly lower plasma biopterin than GG patients and controls. In additional
      samples we assessed the relationship between genotype and diagnosis
      (schizophrenia or control) on GCH1 expression in the prefrontal cortex (n = 67)
      and peripheral leukocytes (n = 53). We found a significant linear relationship
      between GCH1 and study group in the CNS and periphery, with A allele patients
      having lower expression. Finally, in antipsychotic naive patients (n = 13) we
      tested for an effect of medication on GCH1: Expression rose significantly after
      the onset of medication, primarily in A allele patients. These data suggest the
      potential for personalized genetic approaches to ameliorating BH4 deficits in
      schizophrenia-spectrum disorders.

PMID- 29471263
TI  - Predictive models for tyrosinase inhibitors: Challenges from heterogeneous
      activity data determined by different experimental protocols.
AB  - Quantitative Structure-Activity Relationship (QSAR) models of tyrosinase
      inhibitors were built using Random Forest (RF) algorithm and evaluated by the out
      of-bag estimation (R2OOB) and 10-fold cross validation (Q2CV). We found that the
      performances of QSAR models were closely correlated with the systematic errors of
      inhibitory activities of tyrosinase inhibitors arising from the different
      measuring protocols. By defining ERRsys, outliers with larger errors can be
      efficiently identified and removed from heterogeneous activity data. A reasonable
      QSAR model (R2OOB of 0.74 and Q2CV of 0.80) was obtained by the exclusion of 13
      outliers with larger systematic errors. It is a clear example of the challenge
      for QSAR model that can overwhelm heterogeneous data from different experimental
      protocols.

PMID- 29471264
TI  - Collective transcriptomic deregulation of hypertrophic and dilated cardiomyopathy
      - Importance of fibrotic mechanism in heart failure.
AB  - Myocardial fibrosis reside a common pathological feature in hypertrophic and
      dilated cardiomyopathy that results in ventricular dysfunction leading to heart
      failure. Though several studies reported the role of fibrosis in cardiac
      diseases, their pathologic mechanisms leading to heart failure remains unclear. A
      few studies have proposed integrated analysis of microarray information and
      protein-protein interaction (PPI) systems to discover subnetwork markers related
      to diagnosis and prognosis of the disease. In addition to PPI networks, we
      incorporated miRNAs and transcription factors to find the putative miRNAs and
      transcription factors that might regulate the pathological process and
      progression of cardiomyopathy and their further progression to heart failure. The
      important submodules from network revealed the significance of Small Leucine Rich
      Proteoglycans (SLRPs), Extracellular matrix (ECM) related proteins and complement
      system in fibrosis. Sequence analysis of different SLRPs suggest that Keratocan
      and Fibromodulin possesses the same collagen binding site. A predicted mechanism
      of TGFbeta1 shows the involvement of different pathway of HCM and DCM in
      progression of heart failure.

PMID- 29471265
TI  - Role of RpoS in stress resistance, quorum sensing and spoilage potential of
      Pseudomonas fluorescens.
AB  - Microorganism activities are considered the main cause of most food spoilage,
      leading to great economic losses. Pseudomonas fluorescens is a Gram-negative
      bacterium that is widely found in food and has high spoilage activity. RpoS is
      considered an important global regulator involved in stress survival and
      virulence in many pathogens. Thus, it is very possible that RpoS plays an
      important role in spoilage regulation in P. fluorescens. In this study an in
      frame deletion mutation of rpoS was constructed to explore its function in P.
      fluorescens. The results showed that RpoS positively regulated the resistance of
      P. fluorescens to H2O2, heat, ethanol and crystal violet, negatively regulated
      the resistance to acetic acid, and had no effect on the resistance to NaCl.
      Further studies indicated that acylated homoserine lactone (AHL) production and
      the transcription levels of five AHL-related genes were significantly decreased
      in the rpoS mutant compared with those in the wild-type strain. Interestingly,
      the two homologous genes coding for AHL synthases contained RpoS-dependent -10
      elements, suggesting that AHL quorum sensing is directly regulated by RpoS. RpoS
      also contributed to the spoilage activities of P. fluorescens by regulating
      extracellular protease and total volatile basic nitrogen (TVB-N) production in
      sterilized salmon juice. Our results reveal that RpoS was a key regulatory factor
      involved in stress resistance, the AHL quorum sensing system, and spoilage
      potential of P. fluorescens. Our study may benefit food safety control and food
      preservation.

PMID- 29471266
TI  - Genetic characterization of respiratory syncytial virus highlights a new BA
      genotype and emergence of the ON1 genotype in Lyon, France, between 2010 and
      2014.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is a well-recognized cause of
      respiratory tract infections. Based on G gene variations, 11 RSV-A and 36 RSV-B
      genotypes have been described to date. The ON1 genotype was detected in Ontario
      in 2010 and subsequently reported in several countries. OBJECTIVES: The objective
      of the present study was to investigate for the first time the RSV epidemiology
      and genotype diversity in France between 2010 and 2014. STUDY DESIGN: All
      respiratory samples received from patients with influenza-like illness or
      respiratory tract infection were screened for RSV infection by RT-PCR. The
      results were stratified according to winter season. Among the RSV-positive cases,
      117 samples were further investigated for phylogenetic analysis out of 150
      randomly selected for sequencing. RESULTS: Among the 20,359 cases screened, 14%
      of the cases were RSV-positive. RSV-A was predominant during the four winter
      seasons. The first ON1 variant was detected during the 2010-2011 winter and
      reached 85% of all RSV-A-positive cases in 2013-2014. Most RSV-B was classified
      as BA9 and BA10 genotypes but a new genotype (BA-Ly) was described. CONCLUSION:
      As reported in different countries, ON1 variants were firstly detected in 2011
      and became the predominant RSV-A genotype in Lyon. Among RSV-B, BA9 was
      predominant but detected alongside BA10 or a transient genotype (BA-Ly).

PMID- 29471267
TI  - The effectiveness of traditional Chinese medicine-based lifestyle interventions
      on biomedical, psychosocial, and behavioral outcomes in individuals with type 2
      diabetes: A systematic review with meta-analysis.
AB  - BACKGROUND: Integrative diabetes care, which combines conventional diabetes
      therapy with traditional Chinese medicine (TCM)-based interventions, has gained
      popularity worldwide. Numerous TCM-based lifestyle modification approaches have
      been proposed for individuals with type 2 diabetes (T2DM). OBJECTIVES: To
      synthesize and present the best available evidence on the effectiveness of TCM
      based lifestyle interventions in individuals with T2DM. DESIGN: We undertook a
      systematic review of randomized controlled trials or controlled clinical trials.
      DATA SOURCES: Six English and four Chinese electronic databases were searched
      from their inceptions to December 2016. REVIEW METHODS: Trials investigating the
      effectiveness of various TCM-based lifestyle interventions among adults with T2DM
      were reviewed. Studies were excluded if TCM-based lifestyle interventions were
      only part of the intervention regimen. Two reviewers independently selected
      studies according to pre-specified inclusion and exclusion criteria and appraised
      the risk of bias of the included studies. One reviewer extracted details of the
      included studies and the second reviewer checked the extracted data critically.
      When feasible, data were statistically pooled for meta-analysis. Otherwise,
      narrative summaries were used. RESULTS: Twenty-four studies were included. The
      pooled analysis of the eight studies on tai chi showed tai chi practice for at
      least 150 min per week was beneficial in lowering glycosylated hemoglobin (mean
      difference, -1.48%; 95%CI, -2.58% to -0.39%; p < 0.001). Tai chi was effective in
      reducing fasting blood glucose (mean difference, -1.14 mmol/L; 95%CI, -1.78 to 
      0.50 mmol/L; p < 0.001) and body mass index (mean difference, -0.62; 95%CI, -1.14
      to -0.11; p = 0.02), and improving quality of life. The effects of tai chi on
      blood pressure and waist circumference were inconclusive due to the limited
      number of studies. The meta-analysis of the 12 studies on ba duan jin
      demonstrated beneficial effects on glycosylated hemoglobin (mean difference, 
      0.77%; 95%CI, -0.97% to -0.56%; p < 0.001), fasting blood glucose (mean
      difference, -0.82 mmol/L; 95%CI, -1.05 to -0.59 mmol/L; p < 0.001), body mass
      index (mean difference, -2.77; 95%CI, -4.11 to -1.43; p < 0.001), and depression
      (mean difference, -4.53; 95%CI, -7.12 to -1.94; p < 0.001). Conclusions on the
      effects of ba duan jin on quality of life cannot be drawn because only two
      studies measured the outcome. Evidence regarding the effectiveness of other TCM
      based lifestyle interventions is limited. CONCLUSIONS: Tai chi and ba duan jin
      are potentially effective options for individuals with T2DM to improve biomedical
      and psychosocial well-being. Further well-designed studies are needed to explore
      the optimal intervention dose and to investigate the effectiveness of other TCM
      based lifestyle interventions.

PMID- 29471268
TI  - Clydonella sawyeri n. sp. (Amoebozoa, Vannellida): Morphological and molecular
      study and a re-definition of the genus Clydonella Sawyer, 1975.
AB  - We isolated and described a brackish-water amoeba, Clydonella sawyeri n. sp.
      (Amoebozoa, Vannellida), from the littoral habitat in Kandalaksha Bay (The White
      Sea, northwestern Russia). Morphology of this amoeba corresponds to the initially
      proposed diagnosis of the genus Clydonella Sawyer, 1975, although it is
      sufficiently different from other described species of this genus to warrant a
      distinct species designation. Phylogenetic analysis based on the small-subunit
      rRNA gene shows that this species is closely related to the two previously
      studied ATCC strains identified as Clydonella sp., for which only ultrastructural
      and molecular data were published. Cytochrome oxidase subunit 1 (COI) gene
      sequence of the studied species was for the first time obtained for Clydonella.
      Analysis of this marker shows that this genus belongs to Vannellida and is
      separated from the other vannellids sampled to date. Phylogenetic analysis of the
      concatenated SSU rRNA and COI genes dataset yields the best resolved position of
      Clydonella compared to both markers when analysed separately. Based on the data
      presented we finally link light microscopic, ultrastructural and molecular data
      in a description of a single strain, which allows a refinement of the diagnosis
      of the genus Clydonella.

PMID- 29471269
TI  - How to build a phagosome: new concepts for an old process.
AB  - Phagocytosis is a complex and elegant mechanism requiring finely coordinated
      deformation and restructuring of the membrane and the underlying cytoskeleton.
      Here we discuss the early events of receptor clustering and engagement required
      for signal transduction and actin remodeling. In addition, we summarize recent
      studies of the mechanisms whereby the nascent phagosome seals and evolves into a
      degradative phagolysosome by a process that seemingly involves the autophagic
      machinery. These studies provided new insights of the molecular basis of this
      long-appreciated, essential homeostatic process.

PMID- 29471270
TI  - Validation of time to task performance assessment method in simulation: A
      comparative design study.
AB  - BACKGROUND: There is a lack of objective and valid measures for assessing nursing
      clinical competence which could adversely impact patient safety. Therefore, we
      evaluated an objective assessment of clinical competence, Time to Task (ability
      to perform specific, critical nursing care activities within 5 min), and compared
      it to two subjective measures, (Lasater Clinical Judgement Rubric [LCJR] and
      common "pass/fail" assessment). DESIGN/METHODS: Using a prospective, "Known
      Groups" (Expert vs. Novice nurses) comparative design, Expert nurses (ICU nurses
      with >5 years of ICU experience) and Novice nurses (senior prelicensure nursing
      students) participated individually in a simulation of a patient in decompensated
      heart failure. Fourteen nursing instructors or preceptors, blinded to group
      assignment, reviewed 28 simulation videos (15 Expert and 13 Novice) and scored
      them using the LCJR and pass/fail assessments. Time to Task assessment was scored
      based on time thresholds for specific nursing actions prospectively set by an
      expert clinical panel. Statistical analysis consisted of Medians Test and
      sensitivity and specificity analyses. RESULTS: The LCJR total score was
      significantly different between Experts and Novices (p < 0.01) and revealed
      adequate sensitivity (ability to correctly identify "Expert" nurses; 0.72) but
      had a low specificity (ability to correctly identify "Novice" nurses; 0.40). For
      the subjective measure 'pass/fail', sensitivity was high (0.90) but specificity
      was low (0.47). The Time to Task measure had statistical significance between
      Expert and Novice groups (p < 0.01) and sensitivity (0.80) and specificity (0.85)
      were good. CONCLUSION: Commonly used subjective measures of clinical nursing
      competence have difficulties with achieving acceptable specificity. However, an
      objective measure, Time to Task, had good sensitivity and specificity in
      differentiating between groups. While more than one assessment instrument should
      be used to determine nurse competency, an objective measure, such as Time to
      Task, warrants further study.

PMID- 29471271
TI  - Design thinking: Opportunities for application in nursing education.

PMID- 29471272
TI  - Gene architecture and expression analyses provide insights into the role of
      glutathione peroxidases (GPXs) in bread wheat (Triticum aestivum L.).
AB  - Glutathione peroxidases (GPXs) are redox sensor proteins that maintain a steady
      state of H2O2 in plant cells. They exhibit distinct sub-cellular localization and
      have diverse functionality in response to different stimuli. In this study, a
      total of 14 TaGPX genes and three splice variants were identified in the genome
      of Triticum aestivum and evaluated for various physicochemical properties. The
      TaGPX genes were scattered on the various chromosomes of the A, B, and D sub
      genomes and clustered into five homeologous groups based on high sequence
      homology. The majority of genes were derived from the B sub-genome and localized
      on chromosome 2. The intron-exon organization, motif and domain architecture, and
      phylogenetic analyses revealed the conserved nature of TaGPXs. The occurrence of
      both development-related and stress-responsive cis-acting elements in the
      promoter region, the differential expression of these genes during various
      developmental stages, and the modulation of expression in the presence of biotic
      and abiotic stresses suggested their diverse role in T. aestivum. The majority of
      TaGPX genes showed higher expression in various leaf developmental stages.
      However, TaGPX1-A1 was upregulated in the presence of each abiotic stress
      treatment. A co-expression analysis revealed the interaction of TaGPXs with
      numerous development and stress-related genes, which indicated their vital role
      in numerous biological processes. Our study revealed the opportunities for
      further characterization of individual TaGPX proteins, which might be useful in
      designing future crop improvement strategies.

PMID- 29471273
TI  - Effect of simultaneously induced environmental stimuli on electrical signalling
      and gas exchange in maize plants.
AB  - Electrical signalling in response to environmental stimuli is a well-known
      phenomenon in higher plants. For example, in maize, different stimuli, such as
      wounding or re-irrigation after drought, incite characteristic electrical signals
      which have quite particular effects on gas exchange. What is less well understood
      is how plants (specifically maize) respond when two different environmental
      stimuli are applied simultaneously. To explore this, a three-stage experiment was
      designed. In the first stage, drought conditions were simulated by decreasing the
      soil water content to 30-40 % of field capacity. In these conditions, and in
      contrast to well-watered plants, the maize exhibited only 60-70% of the original
      level of stomatal conductance and 50-60 % of the original photosynthesis rate. In
      the second stage of the experiment the plants were re-irrigated and heat
      stimulated separately. Re-irrigation led to specific electrical signals followed
      by a gradual increase of gas exchange. In contrast, after heat stimulation of a
      leaf an electrical signal was evoked that reduced the net CO2-uptake rate as well
      as stomatal conductance. In the third stage, to elucidate how plants process
      simultaneous re-irrigation and heat stimulation, the drought-stressed maize
      plants were re-watered and heat-stimulated at the same time. Results showed a two
      phase response. In the first phase there was a rapid decrease in both the CO2
      uptake rate and the stomatal conductance, while in the second phase each of these
      parameters increased gradually. Thus, the results strongly support the view that
      the responses from both stimuli were combined, indicating that maize plants can
      process simultaneously applied stimuli.

PMID- 29471274
TI  - Accession-specific life strategies affect responses in leaves of Arabidopsis
      thaliana plants exposed to excess Cu and Cd.
AB  - The natural accession Columbia (Col-0) is considered as the reference genome of
      the model plant Arabidopsis thaliana. Nonetheless, Col-0 plants are more
      sensitive to excess copper (Cu) and cadmium (Cd) than other widely used
      accessions such as Wassilewskija (Ws) plants. In the current study, this
      accession-specific metal sensitivity is further explored by comparing the
      responses in leaves of Col-0 and Ws plants exposed to excess Cu and Cd. Our
      results suggest that different life strategies favored by both accessions under
      physiological conditions affect their response to metal exposure. While Col-0
      plants mainly invest in metal detoxification, Ws plants center on nutrient
      homeostasis. In particular, the higher expression of genes related to Cu
      homeostasis genes in non-exposed conditions indicates that Ws plants possess a
      constitutively efficient metal homeostasis. On the other hand, oxidative stress
      related MAPK signaling appears to be boosted in leaves of Col-0 plants exposed to
      excess Cu. Furthermore, the upregulation of the glutathione (GSH) biosynthesis
      GSH2 gene and the increased GSH concentration after Cd exposure suggest the
      activation of detoxification mechanisms, such as phytochelatin production, to
      counteract the more severe Cd-induced oxidative stress in leaves of Col-0 plants.
      Exposure to Cd also led to a more pronounced ethylene signaling response in
      leaves of Col-0 as compared to Ws plants, which could be related to Cd-induced
      GSH metabolism. In conclusion, accession-specific life strategies clearly affect
      the way in which leaves of A. thaliana plants cope with excess Cu and Cd.

PMID- 29471275
TI  - Frequency-agile gyrotron for electron decoupling and pulsed dynamic nuclear
      polarization.
AB  - We describe a frequency-agile gyrotron which can generate frequency-chirped
      microwave pulses. An arbitrary waveform generator (AWG) within the NMR
      spectrometer controls the microwave frequency, enabling synchronized pulsed
      control of both electron and nuclear spins. We demonstrate that the acceleration
      of emitted electrons, and thus the microwave frequency, can be quickly changed by
      varying the anode voltage. This strategy results in much faster frequency
      response than can be achieved by changing the potential of the electron emitter,
      and does not require a custom triode electron gun. The gyrotron frequency can be
      swept with a rate of 20 MHz/MUs over a 670 MHz bandwidth in a static magnetic
      field. We have already implemented time-domain electron decoupling with dynamic
      nuclear polarization (DNP) magic angle spinning (MAS) with this device. In this
      contribution, we show frequency-swept DNP enhancement profiles recorded without
      changing the NMR magnet or probe. The profile of endofullerenes exhibits a DNP
      profile with a <10 MHz linewidth, indicating that the device also has sufficient
      frequency stability, and therefore phase stability, to implement pulsed DNP
      mechanisms such as the frequency-swept solid effect. We describe schematics of
      the mechanical and vacuum construction of the device which includes a novel
      flanged sapphire window assembly. Finally, we discuss how commercially available
      continuous-wave gyrotrons can potentially be converted into similar frequency
      agile high-power microwave sources.

PMID- 29471276
TI  - Optimized phases for the acquisition of J-spectra in coupled spin systems for
      thermally and PHIP polarized molecules.
AB  - We demonstrate that the relative phases in the refocusing pulses of multipulse
      sequences can compensate for pulse errors and off-resonant effects, which are
      commonly encountered in J-spectroscopy when CPMG is used for acquisition. The use
      of supercycles has been considered many times in the past, but always from the
      view point of time-domain NMR, that is, in an effort to lengthen the decay of the
      magnetization. Here we use simple spin-coupled systems, in which the quantum
      evolution of the system can be simulated and contrasted to experimental results.
      In order to explore fine details, we resort to partial J-spectroscopy, that is,
      to the acquisition of J-spectra of a defined multiplet, which is acquired with a
      suitable digital filter. We unambiguously show that when finite radiofrequency
      pulses are considered, the off-resonance effects on nearby multiplets affects the
      dynamics of the spins within the spectral window under acquisition. Moreover, the
      most robust phase cycling scheme for our setup consists of a 4-pulse cycle, with
      phases yyyy? or xxxx? for an excitation pulse with phase x. We show simulated and
      experimental results in both thermally polarized and PHIP hyperpolarized systems.

PMID- 29471277
TI  - Simultaneous acquisition for T2-T2 Exchange and T1-T2 correlation NMR
      experiments.
AB  - The NMR measurements of longitudinal and transverse relaxation times and its
      multidimensional correlations provide useful information about molecular
      dynamics. However, these experiments are very time-consuming, and many
      researchers proposed faster experiments to reduce this issue. This paper presents
      a new way to simultaneously perform T2-T2 Exchange and T1-T2 correlation
      experiments by taking the advantage of the storage time and the two steps phase
      cycling used for running the relaxation exchange experiment. The data
      corresponding to each step is either summed or subtracted to produce the T2-T2
      and T1-T2 data, enhancing the information obtained while maintaining the
      experiment duration. Comparing the results from this technique with traditional
      NMR experiments it was possible to validate the method.

PMID- 29471278
TI  - Intestinal bacteria in bioaerosols and factors affecting their survival in two
      oxidation ditch process municipal wastewater treatment plants located in
      different regions.
AB  - Samples from two oxidation ditch process municipal wastewater treatment plants
      (MWTPs) (HJK and GXQ) in two regions of China were analysed for bacteria,
      particles, total organic carbon, and water-soluble ions in bioaerosols. Diversity
      and potential pathogen populations were evaluated by high-throughput sequencing.
      Bioaerosol sources, factors affecting intestinal bacterial survival, and the
      relationship between bioaerosols and water were analysed by Source tracker and
      partial least squares-discriminant, principal component, and canonical
      correspondence analyses. Culturable bacteria concentrations were 110-846 and 27
      579 CFU/m3 at HJK and GXQ, respectively. Intestinal bacteria constituted 6-33% of
      bacteria. Biochemical reaction tank, sludge dewatering house (SDH), and fine
      screen samples showed the greatest contribution to bioaerosol contamination.
      Enterobacter aerogenes was the main intestinal bacteria (> 99.5%) in HJK and
      detected at each sampling site. Enterobacter aerogenes (98.67% in SDH), Aeromonas
      sp. (76.3% in biochemical reaction tank), and Acinetobacter baumannii (99.89% in
      fine screens) were the main intestinal bacteria in GXQ. Total suspended
      particulate masses in SDH were 229.46 and 141.6 MUg/m3 in HJK and GXQ,
      respectively. Percentages of insoluble compounds in total suspended particulates
      decreased as height increased. The main soluble ions in bioaerosols were Ca2+,
      Na+, Cl-, and SO42-, which ranged from 3.8 to 27.55 MUg/m3 in the MWTPs. Water
      was a main source of intestinal bacteria in bioaerosols from the MWTPs.
      Bioaerosols in HJK but not in GXQ were closely related. Relative humidity and
      some ions positively influenced intestinal bacteria in bioaerosols, while wind
      speed and solar illumination had a negative influence.

PMID- 29471279
TI  - Sequenced ascorbate-proline-glutathione seed treatment elevates cadmium tolerance
      in cucumber transplants.
AB  - During its life cycle, plant has to cope with a number of abiotic stresses
      including cadmium stress. Cadmium (Cd) is highly toxic to plant and greatly
      influences its growth and entire metabolism. Antioxidants have to enable plant to
      beat such stresses. Therefore, effects of ascorbate (AsA), proline (Pro) and
      glutathione (GSH) applied, as seed soaking solutions, singly or in a sequence on
      cucumber transplant growth, physio-biochemical attributes and antioxidant defense
      system activity were investigated under 2 mM Cd stress. Adding Cd to transplants
      in irrigation water reduced photosynthetic efficiency, and nutrient (K+ and Ca2+)
      contents, while increased the activity of defense systems (non-enzymatic and
      enzymatic antioxidants) and Cd2+ contents in roots and leaves. Exogenous AsA, Pro
      and GSH applied singly or in a sequence improved transplant growth (e.g., shoot
      length, leaf area, shoot fresh weight and shoot dry weight), photosynthetic
      efficiency (i.e., SPAD chlorophyll, Fv/Fm and PI), transplant health (i.e.,
      increased leaf MSI and RWC, and decreased root and leaf Cd2+ contents),
      antioxidant defense systems activity (enzymatic; superoxide dismutase, catalase,
      glutathione reductase and ascorbate peroxidase, and non-enzymatic; Pro, AsA and
      GSH antioxidants) and nutrient (K+ and Ca2+) contents. These positive results
      were obtained under irrigation with or without Cd, AsA. Sequenced AsA-Pro-GSH was
      the best treatment of which this study recommends to use, followed by GSH
      treatment, for growing cucumber transplants under Cd stress.

PMID- 29471280
TI  - Stretchable wireless system for sweat pH monitoring.
AB  - Sensor-laden wearable systems that are capable of providing continuous
      measurement of key physiological parameters coupled with data storage, drug
      delivery and feedback therapy have attracted huge interest. Here we report a
      stretchable wireless system for sweat pH monitoring, which is able to withstand
      up to 53% uniaxial strain and more than 500 cycles to 30% strain. The
      stretchability of the pH sensor patch is provided by a pair of serpentine-shaped
      stretchable interconnects. The pH sensing electrode is made of graphite
      polyurethane composite, which is suitable for biosensor application. The sensing
      patch validated through in-depth electrochemical studies, exhibits a pH
      sensitivity of 11.13 +/- 5.8 mV/pH with a maximum response time of 8 s.
      Interference study of ions and analyte (Na+, K+ and glucose) in test solutions
      shows negligible influence on the pH sensor performance. The pH data can be
      wirelessly and continuously transmitted to smartphone through a stretchable radio
      frequency-identification antenna, of which the radiating performance is stable
      under 20% strain, as proved by vector network analyzer measurement. To evaluate
      the full system, the pH value of a human sweat equivalent solution has been
      measured and wirelessly transmitted to a custom-developed smart phone App.

PMID- 29471281
TI  - Theoretical and experimental study for the biomimetic recognition of
      levothyroxine hormone on magnetic molecularly imprinted polymer.
AB  - This study addresses the rational design of a magnetic molecularly imprinted
      polymer (magnetic-MIP) for the selective recognition of the hormone
      levothyroxine. The theoretical study was carried out by the density functional
      theory (DFT) computations considering dispersion interaction energies, and using
      the D2 Grimme's correction. The B97-D/def2-SV(P)/PCM method is used not only for
      studying the structure of the template the and monomer-monomer interactions, but
      also to assess the stoichiometry, noncovalent binding energies, solvation effects
      and thermodynamics properties such as binding energy. Among the 13 monomers
      studied in silico, itaconic acid is the most suitable according to the
      thermodynamic values. In order to assess the efficiency of the computational
      study, three different magnetic-MIPs based on itaconic acid, acrylic acid and
      acrylamide were synthesized and experimentally compared. The theoretical results
      are in agreement with experimental binding studies based on laser confocal
      microscopy, magneto-actuated immunoassay and electrochemical sensing.
      Furthermore, and for the first time, the direct electrochemical sensing of L
      thyroxine preconcentrated on magnetic-MIP was successfully performed on magneto
      actuated electrodes within 30 min with a limit of detection of as low as 0.0356
      ng mL-1 which cover the clinical range of total L-thyroxine. Finally, the main
      analytical features were compared with the gold standard method based on
      commercial competitive immunoassays. This work provides a thoughtful strategy for
      magnetic molecularly imprinted polymer design, synthesis and application, opening
      new perspectives in the integration of these materials in magneto-actuated
      approaches for replacing specific antibodies in biosensors and microfluidic
      devices.

PMID- 29471282
TI  - AuNPs/CNOs/SWCNTs/chitosan-nanocomposite modified electrochemical sensor for the
      label-free detection of carcinoembryonic antigen.
AB  - In this work, a nanocomposite of gold nanoparticles (AuNPs), carbon nano-onions
      (CNOs), single-walled carbon nanotubes (SWCNTs) and chitosan (CS)
      (AuNPs/CNOs/SWCNTs/CS) was prepared for the development of highly sensitive
      electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA),
      clinical tumor marker. Firstly, layer-by-layer fabrication of the CEA
      immunosensors was studied using cyclic voltammetry (CV) and square wave
      voltammetry (SWV). By combining the advantages of large surface area and
      electronic properties of AuNPs, CNOs, SWCNTs, and film forming properties of CS,
      AuNPs/CNOs/SWCNTs/CS-nanocomposite-modified glassy carbon electrode showed a 200%
      increase in effective surface area and electronic conductivity. The calibration
      plot gave a negative linear relationship between log[concentration] of CEA and
      electrical current with a correlation coefficient of 0.9875. The CEA-immunosensor
      demonstrated a wide linear detection range of 100 fg mL-1 to 400 ng mL-1 with a
      low detection limit of 100 fg mL-1. In addition to high sensitivity,
      reproducibility and large stability, CEA-immunosensor provided an excellent
      selectivity and resistant-to-interference in the presence of other antigens in
      serum and hence a potential to be used with real samples.

PMID- 29471283
TI  - Task-residual functional connectivity of language and attention networks.
AB  - Functional connectivity using task-residual data capitalizes on remaining
      variance after mean task-related signal is removed from a time series. The degree
      of network specificity in language and attention domains featured by task
      residual and resting-state data types were compared. Functional connectivity
      based on task-residual data evidenced stronger laterality of the language and
      attention connections and thus greater network specificity compared to resting
      state functional connectivity of the same connections. Covariance between network
      nodes of task-residuals may thus reflect the degree to which two regions are
      coordinated in their specific activity, rather than a general shared co
      activation. Task-residual functional connectivity provides complementary data to
      that of resting-state, emphasizing network relationships during task engagement.

PMID- 29471285
TI  - Effects of docosahexanoic acid supplementation on inflammatory and subcutaneous
      adipose tissue gene expression in HIV-infected patients on combination
      antiretroviral therapy (cART). A sub-study of a randomized, double-blind, placebo
      controlled study.
AB  - BACKGROUND: Omega-3 fatty acids have the potential to decrease inflammation and
      modify gene transcription. Whether docosahexanoic acid (DHA) supplementation can
      modify systemic inflammatory and subcutaneous adipose tissue (SAT) gene
      expression in HIV-infected patients is unknown. METHODS: A randomized, double
      blind, placebo-controlled trial that enrolled 84 antiretroviral-treated patients
      who had fasting TG levels from 2.26 to 5.65 mmol/l and received DHA or placebo
      for 48 weeks was performed (ClinicalTrials.gov, NCT02005900). Systemic
      inflammatory and SAT gene expression was assessed at baseline and at week 48 in
      39 patients. RESULTS: Patients receiving DHA had a 43.9% median decline in
      fasting TG levels at week 4 (IQR: -31% to -56%), compared with -2.9% (-18.6% to
      16.5%) in the placebo group (P < 0.0001). High sensitivity C reactive protein
      (hsCRP) and arachidonic acid levels significantly decreased in the DHA group.
      Adipogenesis-related and mitochondrial-related gene expression did not experience
      significant changes. Mitochondrial DNA (mtDNA) significantly decreased in the
      placebo group. SAT inflammation-related gene expression (Tumor necrosis factor
      alpha [TNF-alpha], and monocyte chemoattractant protein-1 [MCP-1]) significantly
      decreased in the DHA group. CONCLUSIONS: DHA supplementation down-regulated
      inflammatory gene expression in SAT. DHA impact on markers of systemic
      inflammation was restricted to hsCRP and arachidonic acid.

PMID- 29471286
TI  - Advanced MRI study of migrainous infarction presenting as cortical laminar
      necrosis - Case report and literature review.

PMID- 29471284
TI  - Adverse metabolic effects in fish exposed to contaminants of emerging concern in
      the field and laboratory.
AB  - Several metabolic parameters were assessed in juvenile Chinook salmon
      (Oncorhynchus tshawytscha) and staghorn sculpin (Leptocottus armatus) residing in
      two estuaries receiving wastewater treatment effluent and one reference estuary.
      We also conducted a laboratory study with fish dosed for 32 days with 16 of the
      most common contaminants of emerging concern (CECs) detected in feral fish.
      Several blood chemistry parameters and other indicators of health were measured
      in fish from the field and laboratory study that were used to assess potential
      metabolic disruption. The blood chemistry values observed in feral juvenile
      Chinook salmon were relatively consistent among fish collected from effluent
      impacted sites and substantially different compared to reference site fish. These
      responses were more pronounced in Chinook salmon, which is supported by the
      disparity in accumulated CECs. The blood chemistry results for juvenile Chinook
      salmon collected at effluent-impacted sites exhibited a pattern generally
      consistent with starvation because of similarities to observations from studies
      of food-deprived fish; however, this response is not consistent with physical
      starvation but may be contaminant induced. The altered blood chemistry parameters
      are useful as an early indicator of metabolic stress, even though organismal
      characteristics (lipid content and condition factor) were not different among
      sites indicating an early response. Evidence of metabolic disruption was also
      observed in juvenile Chinook salmon that were exposed in the laboratory to a
      limited mixture of CECs; however, the plasma parameters were qualitatively
      different possibly due to exposure route, season, or the suite of CECs. Growth
      was impaired in the high-dose fish during the dosing phase and the low- and
      medium-dose fish assayed after 2 weeks of depuration. Overall, these results are
      consistent with metabolic disruption for fish exposed to CECs, which may result
      in early mortality or an impaired ability to compete for limited resources.

PMID- 29471287
TI  - Preoperative Grading of Glioma Using Dynamic Susceptibility Contrast MRI:
      Relative Cerebral Blood Volume Analysis of Intra-tumoural and Peri-tumoural
      Tissue.
AB  - OBJECTIVES: To assess the usefulness of intra-tumor and peri-tumoral relative
      cerebral blood volume (rCBV) in preoperative glioma grading. PATIENTS AND
      METHODS: 21 patients with histopathologically confirmed glioma were included.
      Imaging was achieved on a 1.5T MRI scanner. Dynamic susceptibility contrast (DSC)
      MRI was performed using T2* weighted gradient echo-planner imaging (EPI).
      Multiple regions of interest (ROIs) have been drawn in the hotspots regions, the
      highest ROI has been selected to represent the rCBV of each intra-tumoral and
      peri-tumoral regions. Based on histopathology, tumors were subdivided into low
      grade and high grade. Receiver operating characteristic analysis (ROC) of rCBV,
      of both intra-tumoral and peri-tumoral regions, was performed to find cut-off
      values between high and low-grade tumors. The resulting sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy were
      calculated. RESULTS: Based on the histopathology, high-grade glioma (HGG)
      represented 76.2% whereas low-grade glioma (LGG) represented 23.8%. Both intra
      tumoral and peri-tumoral rCBV of HGG were significantly higher than those of LGG.
      A cut-off value >2.9 for intra-tumoral rCBV provided sensitivity, specificity,
      and accuracy of 80%, 100%, and 85.7% respectively to differentiate between HGG
      and LGG. Additionally, the cut-off value >0.7 for peri-tumoral rCBV provided
      sensitivity, specificity, and accuracy of 100%, 66.6%, and 90.5% respectively to
      differentiate between HGG and LGG. CONCLUSION: rCBV of each of intra-tumoral and
      peri-tumoral rCBV are significantly reliable for the preoperative distinction
      between HGG and LGG. Combined intra-tumoral and peri-tumoral rCBV provides
      overall better diagnostic accuracy and helps to decrease the invasive
      intervention for non-surgical candidates.

PMID- 29471288
TI  - Clinically aggressive phenotype: A clinicopathological case series of atypical
      pituitary adenomas.
AB  - OBJECTIVE: Atypical pituitary adenomas were relatively more malignant lesions
      defined by WHO criteria. However, not all of them show clinically aggressive
      behavior. Thus, the current WHO criteria of atypical adenoma didn't seem to be
      enough to distinguish clinically aggressive adenoma. Therefore, we would like to
      identify other clinical factors in a cohort of atypical pituitary adenomas to a
      better identification of clinical aggressiveness. PATIENTS AND METHODS: In order
      to verify predictors of clinically aggressive phenotype among atypical pituitary
      adenomas, we retrospectively analyzed the clinical characteristics and
      therapeutic outcomes of consecutive 49 cases. RESULTS: Totally, 26 cases were
      identified as clinically aggressive pituitary adenoma. Clinically aggressive
      lesions were more likely to be functional (46.2% vs. 17.4%, p = .0388) and be
      detected in males (65.4% vs. 21.7%, p = .0037). Clinically aggressive adenomas
      also had higher Ki-67 index [5.0 (5.3)% vs. 4.1 (1.3)%, p = .0011] and presented
      bigger tumor size [11.83 (11.95) cm3 vs. 5.39 (6.08) cm3, p = .0174]. In
      multivariate analysis, gender (p = .017), functional status (p = .009) and Ki-67
      index (p = .024) were independent predictors of clinical aggressiveness. Further
      analysis revealed that Ki-67 index of more than 4.45% was associated with worse
      progression-free survival. CONCLUSIONS: Gender, functional status, tumor size and
      Ki-67 index >=4.45% were associated with clinical aggressiveness. A
      clinicopathological classification of pituitary adenomas may be useful to
      determine who should be under closer radiological follow-up or followed
      multimodal treatment strategy.

PMID- 29471290
TI  - Presence of Kidney Disease as an Outcome Predictor in Patients with Pulmonary
      Arterial Hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) may lead to right heart failure
      and subsequently alter glomerular filtration rates (GFR). Chronic kidney disease
      (CKD, GFR <60 mL/min/1.73 m2) may also adversely affect PAH prognosis. This study
      aimed to assess how right heart hemodynamics was associated with reduced
      estimated GFR (eGFR) and the association of CKD with survival in PAH patients.
      METHODS: In a prospective PAH cohort (2003-2012), invasive hemodynamics and eGFR
      were collected at diagnosis (179 patients) and during follow-up (159 patients).
      The prevalence of CKD was assessed at PAH diagnosis. Variables, including
      hemodynamics, associated with reduced eGFR at diagnosis and during follow-up were
      tested in multivariate analysis. The association of CKD with survival was
      evaluated using a multivariate Cox regression model. RESULTS: At diagnosis, mean
      age was 60.4 +/- 16.5 years, mean pulmonary arterial pressure was 43 +/- 12 mm
      Hg, and eGFR was 74.4 +/- 26.4 mL/min/1.73 m2. CKD was observed in 52 incident
      patients (29%). Independent determinants of reduced eGFR at diagnosis were age,
      systemic hypertension, and decreased cardiac index. Independent determinants of
      reduced eGFR during follow-up were age, female gender, PAH etiology, systemic
      hypertension, decreased cardiac index, and increased right atrial pressure. Age
      >=60 years, female gender, NYHA 4, and CKD at diagnosis were independently
      associated with decreased survival. The adjusted hazards ratio for death
      associated with CKD was 1.81 (95% confidence interval [1.01-3.25]). CONCLUSION:
      CKD is frequent at PAH diagnosis and is independently associated with increased
      mortality. Right heart failure may induce renal hypoperfusion and congestion, and
      is associated with eGFR decrease.

PMID- 29471289
TI  - Single Nucleotide Polymorphism Facilitated Down-Regulation of the Cohesin Stromal
      Antigen-1: Implications for Colorectal Cancer Racial Disparities.
AB  - The biological underpinnings for racial disparities in colorectal cancer (CRC)
      incidence remain to be elucidated. We have previously reported that the cohesin
      SA-1 down-regulation is an early event in colon carcinogenesis which is
      dramatically accentuated in African-Americans. In order to investigate the
      mechanism, we evaluated single nucleotide polymorphisms (SNPs) for association
      with SA-1-related outcomes followed by gene editing of candidate SNP. We observed
      that rs34149860 SNP was significantly associated with a lower colonic mucosal SA
      1 expression and evaluation of public databases showed striking racial
      discordance. Given that the predicted SNP would alter miR-29b binding site, we
      used CRISPR knock-in in CRC cells and demonstrated that the SNP but not wild-type
      had profound alterations in SA-1 expression with miR-29b inhibitor. This is the
      first demonstration of high-order chromatin regulators as a modulator of racial
      differences, risk alteration with SNPs and finally specific modulation by
      microRNAs.

PMID- 29471292
TI  - Step Numbers and Hoehn-Yahr Stage after Six Years.
AB  - BACKGROUND: Freezing of gait (FOG) has been linked to increased numbers of steps
      taken while walking. We tested the hypothesis that an increased number of steps
      associated with FOG might predict the exacerbation of the severity of Parkinson's
      disease (PD). METHODS: We prospectively studied 26 patients. Clinical assessments
      were performed and balance was evaluated in 30 patients with Hoehn-Yahr stage III
      PD 6 years previously. Gait parameters were analyzed with the use of an
      originally designed, suddenly narrowed path. PD-related independent variables,
      balance investigation-related variables, and gait-independent-related variables
      were analyzed by multiple logistic regression analysis. RESULTS: The Hoehn-Yahr
      stage increased in 14 patients and was unchanged in 12 patients. The 36-item
      Short-Form Health Survey score (OR 1.079, p = 0.041, 95% CI 1.003-1.161) and the
      number of steps on the suddenly narrow path (OR 1.605, p = 0.047, 95% CI 1.006
      2.56) were related to an increase in the Hoehn-Yahr stage. The number of steps
      was significantly higher on the suddenly narrowed path (11.3 +/- 3.6) than on a
      straightly narrowed path (10.1 +/- 3.2) at the time of final follow-up in the 26
      patients (p < 0.001). CONCLUSIONS: An increased number of steps associated with
      FOG, which was elicited by the suddenly narrowed path, might be one predictor of
      an upgrade of stage in patients with Hoehn-Yahr stage III PD.

PMID- 29471293
TI  - Neonatal Stress Has a Long-Lasting Sex-Dependent Effect on Anxiety-Like Behavior
      and Neuronal Morphology in the Prefrontal Cortex and Hippocampus.
AB  - The long-lasting effects of early stress on brain development have been well
      studied. Recent evidence indicates that males and females respond differently to
      the same stressor. We examined the chronic effects of daily maternal separation
      (MS) on behavior and cerebral morphology in both male and female rats. Cognitive
      and anxiety-like behaviors were evaluated, and neuroplastic changes in 2
      subregions of the prefrontal cortex (dorsal agranular insular cortex [AID] and
      cingulate cortex [Cg3]) and hippocampus (CA1 and dentate gyrus) were measured in
      adult male and female rats. The animals were subjected to MS on postnatal day (P)
      3-14 for 3 h per day. Cognitive and emotional behaviors were assessed in the
      object/context mismatch task, elevated plus maze, and locomotor activity test in
      early adulthood (P87-P95). Anatomical assessments were performed in the
      prefrontal cortex (i.e., cortical thickness and spine density) and hippocampus
      (i.e., spine density). Sex-dependent effects were observed. MS increased anxiety
      related behavior only in males, whereas locomotor activity was higher in females,
      with no effects on cognition. MS decreased spine density in the AID and increased
      spine density in the CA1 area in males. Females exhibited an increase in spine
      density in the Cg3. Our findings confirm previous work that found that MS causes
      long-term behavioral and anatomical effects, and these effects were dependent on
      sex and the duration of MS stress.

PMID- 29471294
TI  - Novel Familial Variant of the Desert Hedgehog Gene: Clinical Findings in Two
      Sisters with 46,XY Gonadal Dysgenesis or 46,XX Karyotype and Literature Review.
AB  - BACKGROUND: In humans, Desert Hedgehog (DHH) gene mutations are a very rare cause
      of 46,XY gonadal dysgenesis (GD), eventually associated with peripheral
      neuropathy. PATIENTS AND METHODS: Clinical records of 12 patients with 46,XY GD
      and unknown genetic background were reviewed and a 46,XY woman with peripheral
      neuropathy was individuated. Her 46,XX sister affected by similar neuropathy was
      also investigated. Genomic DNA was extracted and DHH exons sequenced and
      analyzed. A comparative genomic hybridization array was also performed. RESULTS:
      In both the 46,XY and 46,XX sisters, a homozygous c.554C>A mutation in exon 2 of
      the DHH gene was found, determining a premature termination codon (p.Ser 185*).
      Heterozygous consanguineous carrier parents showed neither reproductive problems
      nor peripheral neuropathy. In the proband and her sister, a 499-kb duplication in
      9p22.1 was also found. CONCLUSION: A 46,XY European woman with 46,XY GD and a
      novel homozygous DHH pathogenic variant is reported, confirming that this gene
      plays a key role in male gonadal development. Her 46,XX sister, harboring the
      same mutation, showed normal internal and external female phenotype. Thus, DHH
      seems not to be involved in the ovarian development pathway or its postpubertal
      function. Homozygous DHH mutations cause a specific peripheral neuropathy in
      humans with both 46,XY and 46,XX karyotypes.

PMID- 29471295
TI  - Higher Failure of Endoscopic Third Ventriculostomy in Infants: The "Distensible"
      Skull Is the Culprit.
AB  - The efficacy of endoscopic third ventriculostomy (ETV) in childhood strongly
      correlates with age. Reasons for the higher failure rate in infants are under
      debate but the "distensible" head with its immature skull (which would prevent an
      adequate flow through the ETV and/or a sufficient pressure gradient between the
      cortical subarachnoid spaces and the venous sinuses) has been suggested as a
      possible cause. Our evidence of spontaneous conversion of a failed, but always
      patent, third ventriculostomy into an effective one occurring in a child after
      maturation of the skull supports this hypothesis.

PMID- 29471298
TI  - Abstracts of the 15th Italian Congress of Neuroepidemiology.

PMID- 29471296
TI  - Ambulatory Assessment of Borderline Personality Disorder.
AB  - Ambulatory assessment (AA) is an important tool that promises to minimize
      retrospective biases while gathering ecologically valid data, including self
      reports, physiological or biological data, and observed behavior, for example,
      from daily life experiences. AA is well suited for studying borderline
      personality disorder (BPD) because it can measure moods and emotion (as well as
      dynamic mood processes, mood changes, and mood instability), problematic
      behaviors (including interpersonal conflicts, addictive behaviors, binge and
      purge episodes, and motoric activity), and problematic
      cognitions/expectancies/urges (e.g., rejection sensitivity, cravings, and self
      harm urges) as they occur in daily life. In this article, I review existing AA
      research on BPD, and I discuss future applications of AA as well as limitations
      and considerations for future use.

PMID- 29471299
TI  - The Effect of Allium cepa Extract on Lung Oxidant, Antioxidant, and Immunological
      Biomarkers in Ovalbumin-Sensitized Rats.
AB  - OBJECTIVES: To evaluate the effects of Allium cepa (A. cepa) on levels of
      oxidants, antioxidants, and immunological markers in bronchoalveolar lavage
      fluids (BALF) of sensitized rats. MATERIALS AND METHODS: Oxidant/antioxidant
      markers and cytokines in BALF of control rats treated with saline (group C),
      ovalbumin-sensitized rats (group S), rats treated with 1.25 MUg/mL dexamethasone
      and 3 doses of A. cepa extract (35, 70, and 140 mg/kg body weight [BW]/day) (S +
      AC) were investigated. Comparison of the results between groups was performed
      using analysis of variance with the Tukey-Kramer post hoc test. RESULTS: The
      oxidant markers nitrogen dioxide (NO2), nitrate (NO3-), and malondialdehyde
      (MDA), and immunological markers interleukin (IL)-4 and immunoglobulin E (IgE)
      were significantly higher, but the antioxidant markers superoxide dismutase
      (SOD), catalase (CAT), thiol, and interferon (IFN)-gamma, and the IFN-gamma/IL-4
      ratio were lower in sensitized rats compared to control rats (p < 0.001 to p <
      0.01). Compared to group S, the levels of the following markers were
      significantly lower: NO2, NO3-, and IgE in groups treated with the A. cepa
      extract, MDA and IL-4 levels in groups treated with 70 and 140 mg/kg BW/day of
      the A. cepa extract, and all these markers as well as IFN-gamma in rats treated
      with dexamethasone (p < 0.001 to p < 0.05). However, there were significantly
      higher levels of SOD and CAT and an increased IFN-gamma/IL-4 ratio (groups
      treated with 70 and 140 mg/kg BW/day of the A. cepa extract), and levels of thiol
      and IFN-gamma (group treated with 140 mg/kg BW/day of the A. cepa extract) as
      well as SOD, CAT, and thiol (dexamethasone-treated group) versus group S (p <
      0.00 to p < 0.05). CONCLUSION: A. cepa showed antioxidant and immunomodulatory
      properties in sensitized rats.

PMID- 29471301
TI  - Repeated Bioimpedance Measurements Predict Prognosis of Peritoneal Dialysis
      Patients.
AB  - BACKGROUND: Fluid overload is a major risk factor for mortality in patients
      undergoing peritoneal dialysis (PD). However, few studies have investigated the
      effect of chronic exposure to sustained fluid overload on long-term outcomes.
      METHOD: A total of 284 prevalent PD patients were included in this prospective
      study. Repeated multifrequency body composition analysis was performed 12 months
      apart, and 1-year cumulative chronic fluid overload were used to predict all
      cause mortality and the risk for transfer to hemodialysis (HD) during the ensuing
      15.6 +/- 9.1 months. RESULTS: The prevalence of fluid overload was approximately
      27%. Interestingly, a substantial number of hypervolemic patients at first test
      were persistently hypervolemic at their second test. With this, chronic fluid
      overload was observed in 18.3% (n = 52). Notably, most of chronic fluid overload
      patients had diabetes (86.5%), and it was accompanied by concomitant changes in
      peritoneal membrane characteristics, a higher progression rate to high
      transporter. The risk of transfer to HD increased 2.8 times in patients with
      chronic fluid overload than in those without. Also, it significantly increased
      the risk of mortality (p = 0.038). Surprisingly, subgroup analysis found that
      patients with euvolemic status at follow-up experienced no mortality despite
      being in a fluid overload state at baseline. CONCLUSIONS: One-year chronic
      exposure to fluid overload is a strong independent risk factor for transfer to HD
      and death in prevalent PD patients. Although the fluid status of most PD patients
      is not easily changed over time, becoming euvolemic during the entire PD
      treatment period seems to be very important.

PMID- 29471300
TI  - Yttrium-90-Ibritumomab Tiuxetan (Zevalin(r)) Radioimmunotherapy after
      Cytoreduction with ESHAP Chemotherapy in Patients with Relapsed Follicular Non
      Hodgkin Lymphoma: Final Results of a Phase II Study.
AB  - BACKGROUND: Radioimmunotherapy (RIT) is effective in treating relapsed/refractory
      follicular lymphoma (FL), with durable remissions in first-line consolidation. We
      hypothesized that RIT with ibritumomab tiuxetan (Zevalin(r)) would result in
      durable remissions by eliminating minimal residual disease after cytoreduction.
      METHODS: Patients with FL received 2 cycles of ESHAP (etoposide,
      methylprednisolone, cytarabine, cisplatin) every 28 days, followed by Zevalin 4-6
      weeks later if there was no disease progression and bone marrow biopsy showed <
      25% involvement. RESULTS: Twenty-eight patients were treated, with a median age
      of 61 years, median of 3 prior therapies, 49% high-risk disease (Follicular
      Lymphoma International Prognostic Index, FLIPI), and 39% progressive disease.
      Three patients did not receive Zevalin due to residual bone marrow involvement.
      The main toxicities were cytopenias, with 11% febrile neutropenia. The overall
      response rate (ORR) was 72%, with 45% achieving complete response. With a median
      follow-up of 73 months, 1-year progression-free survival (PFS) was 38%, and
      median PFS was 10 months, but median overall survival (OS) was not reached.
      CONCLUSION: The study did not reach its primary endpoint of a 1-year PFS of
      67.3%. Reasons for this could include low accrual, high-risk disease, and
      inadequate debulking provided by 2 cycles of ESHAP. However, this protocol was
      associated with tolerable toxicity, high ORR, and high OS. Further studies would
      optimize debulking and focus on high-risk FL patients.

PMID- 29471302
TI  - SOCS3 Is Upregulated and Targeted by miR30a-5p in Allergic Rhinitis.
AB  - BACKGROUND: Suppressor of cytokine signaling 1 (SOCS1) and SOCS3 play important
      roles in T helper cell differentiation, which is involved with the pathologic
      mechanisms of allergic rhinitis (AR). The aim of this study was to evaluate the
      expression of SOCS1 and SOCS3 in AR and find their regulatory microRNAs (miRNAs)
      to provide a basis for the treatment of AR. METHODS: The expression of SOCS1 and
      SOCS3 were analyzed by real-time PCR, immunohistochemistry, and Western blot. The
      correlative regulatory miRNAs were detected by real-time PCR. Luciferase assays
      and AR mouse model experiments were applied to identify correlative miRNAs that
      target SOCS3. RESULTS: SOCS1 and SOCS3 mRNA were upregulated in the nasal mucosa
      and peripheral blood mononuclear cells of AR compared with controls. The
      expression of SOCS3 protein was significantly increased in the nasal mucosa of
      AR. The immunohistochemical staining results showed that SOCS3 was similarly
      localized in the superficial epithelium, submucosal glands, and vascular
      endothelium in the nasal mucosa of AR subjects and controls. However, SOCS3
      protein was especially localized in the inflammatory cells, such as eosinophils,
      monocytes, and lymphocytes. CONCLUSIONS: SOCS3 was targeted by miR30a- 5p in AR.
      Further study should be performed to identify the regulatory effect of miR30a-5p
      in AR, which may provide insights into a new therapeutic strategy.

PMID- 29471303
TI  - Awareness of the New Kidney Allocation System among United States Dialysis
      Providers with Low Waitlisting.
AB  - It is unknown whether dialysis facility staff are aware of the new kidney
      allocation system implemented in December 2014, which changed how deceased donor
      kidneys are allocated and waiting time is calculated. U.S. dialysis facilities
      with low annual waitlisting (<15.2%) were surveyed as part of a large randomized
      study. Among 653 facilities, 57.9% of staff were aware of the policy change, with
      medical directors (84.4%) being more aware than social workers (73.3%), facility
      administrators (53.1%), nurse managers (46.4%), and other staff (43.8%). Targeted
      education among dialysis facilities with low waitlisting may help extend the
      reach of the new policy.

PMID- 29471304
TI  - Pulmonary Arterial Hypertension and the Kidney: Getting to the Heart of the
      Matter.

PMID- 29471305
TI  - Humanized Exposures of Cefiderocol, a Siderophore Cephalosporin, Display
      Sustained in vivo Activity against Siderophore-Resistant Pseudomonas aeruginosa.
AB  - We evaluated the in vivo efficacy of humanized exposures of cefiderocol, a novel
      siderophore cephalosporin, against a test panel of P. aeruginosa (PSA) previously
      shown to develop resistance to 2 preclinical candidate siderophores (MB-1 and SMC
      3176). In the thigh infection model, the PSA bacterial density in untreated
      controls grew from 5.54 +/- 0.23 to 8.68 +/- 0.57 log10 CFU over 24 h. The
      humanized cefiderocol exposure resulted in >1 log10 CFU reduction in all 8
      isolates, while MB-1 and SMC-3176 exhibited variable activity similar to that
      previously reported. Humanized exposures of cefepime and levofloxacin, acting as
      positive antimicrobial controls displayed activity consistent with that of the
      bacterial phenotypic susceptibility profiles. Cefiderocol manifested in vivo
      efficacy against all PSA isolates including those resistant to cefepime and
      levofloxacin in contrast to its predecessor siderophore compounds. These
      preclinical data are supportive of further evaluation of cefiderocol in the
      treatment of P. aeruginosa.

PMID- 29471307
TI  - EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting.

PMID- 29471308
TI  - Reporting guidelines for oncology research: helping to maximise the impact of
      your research.
AB  - Many reports of health research omit important information needed to assess their
      methodological robustness and clinical relevance. Without clear and complete
      reporting, it is not possible to identify flaws or biases, reproduce successful
      interventions, or use the findings in systematic reviews or meta-analyses. The
      EQUATOR Network (http://www.equator-network.org/) promotes responsible reporting
      and the use of reporting guidelines to improve the accuracy, completeness, and
      transparency of health research. EQUATOR supports researchers by providing online
      resources and training. EQUATOR Oncology, a project funded by Cancer Research UK,
      aims to support cancer researchers reporting their research through the provision
      of online resources. In this article, our objective is to highlight reporting
      issues related to oncology research publications and to introduce reporting
      guidelines that are designed to aid high-quality reporting. We describe generic
      reporting guidelines for the main study types, and explain how these guidelines
      should and should not be used. We also describe 37 oncology-specific reporting
      guidelines, covering different clinical areas (e.g., haematology or urology) and
      sections of the report (e.g., methods or study characteristics); most of these
      are little-used. We also provide some background information on EQUATOR Oncology,
      which focuses on addressing the reporting needs of the oncology research
      community.

PMID- 29471309
TI  - The role of the diet in tooth wear.
AB  - An acidic diet has been associated with erosive tooth wear. However, some people
      who consume dietary acids develop erosive tooth wear and some do not. This review
      paper provides an overview of the risk factors of dietary acid consumption which
      increase the likelihood of developing severe erosive tooth wear. Increased
      frequency of dietary acid consumption, particularly between meals appears to be
      the predominant risk factor. However, habitually drinking acidic drinks by
      sipping them slowly or swishing, rinsing or holding acidic drinks in the mouth
      before swallowing will also increase risk of progression. Consuming fruit over
      long time periods at a single sitting and dietary acids being served at increased
      temperatures have also been implicated. Additions of fruit or fruit flavourings
      to drinks and regular consumption of vinegars, pickles, acidic medications or
      acidic sugar-free sweets are potential hidden risk factors that should be
      discussed with patients at risk of erosive tooth wear progression. Behaviour
      change is difficult to achieve but specific, targeted behavioural interventions
      and offering alternatives may increase success.

PMID- 29471317
TI  - Examining Duration of Protection: Should a Booster Dose Be Part of All Infant
      Pneumococcal Conjugate Vaccine Programs?

PMID- 29471310
TI  - Age-related reduction of trunk muscle torque and prevalence of trunk sarcopenia
      in community-dwelling elderly: Validity of a portable trunk muscle torque
      measurement instrument and its application to a large sample cohort study.
AB  - Trunk muscle weakness and imbalance are risk factors for postural instability,
      low back pain, and poor postoperative outcomes. The association between trunk
      muscle strength and aging is poorly understood, and establishing normal reference
      values is difficult. We aimed to establish the validity of a novel portable trunk
      muscle torque measurement instrument (PTMI). We then estimated reference data for
      healthy young adults and elucidated age-related weakness in trunk muscle
      strength. Twenty-four university students were enrolled to validate values for
      PTMI, and 816 volunteers from the general population who were recruited to the
      Iwaki Health Promotion Project were included to estimate reference data for trunk
      muscle strength. Trunk flexion and extension torque were measured with PTMI and
      KinCom, and interclass correlation coefficients (ICC) were estimated to evaluate
      the reliability of PTMI values. Furthermore, from the young adult reference, the
      age-related reduction in trunk muscle torque and the prevalence of sarcopenia
      among age-sex groups were estimated. The ICC in flexion and extension torque were
      0.807 (p<0.001) and 0.789 (p<0.001), respectively. The prevalence of sarcopenia
      increased with age, and the prevalence due to flexion torque was double that of
      extension torque. Flexion torque decreased significantly after 60 years of age,
      and extension torque decreased after 70 years of age. In males over age 80, trunk
      muscle torque decreased to 49.1% in flexion and 63.5% in extension. In females
      over age 80, trunk muscle torque decreased to 60.7% in flexion and 68.4% in
      extension. The validity of PTMI was confirmed by correlation with KinCom. PTMI
      produced reference data for healthy young adults, and demonstrated age-related
      reduction in trunk muscle torque. Trunk sarcopenia progressed with aging, and the
      loss of flexion torque began earlier than extension torque. At age 80, trunk
      muscle torque had decreased 60% compared with healthy young adults.

PMID- 29471316
TI  - Influence of Prior Knowledge of Human Papillomavirus Status on the Performance of
      Cytology Screening.
AB  - Objectives: This study aimed to evaluate the influence of prior knowledge of
      human papillomavirus (HPV) status in cervical cytopathology readings. Methods:
      Participants comprised 2,376 women who underwent parallel cytology and HPV-DNA
      testing. Smears were read twice by the same team, first with previous knowledge
      of HPV-DNA status. Results: Overall, 239 (10.2%) smears had their cytology
      classification altered by the HPV-informed review. Cytology readings with prior
      knowledge of the HPV status revealed 10.5% of abnormal smears (atypical squamous
      cells of undetermined significance or higher), while without prior knowledge,
      this rate dropped to 7.6%. When HPV status was informed, a significant increase
      in all categories of altered smears was observed. Cytology with prior knowledge
      of HPV status detected more cervical intraepithelial neoplasia grade 2 or higher
      (CIN 2+) compared with blinded: 86.7% vs 60.0%. Conclusions: Our data indicate
      that cytology interpreted with prior knowledge of the HPV status provides higher
      sensitivity for CIN 2+ lesions while marginally reducing the overall specificity
      compared with HPV status blinded cytology.

PMID- 29471318
TI  - Family physician awareness of Charles Bonnet syndrome.
AB  - Background: Charles Bonnet syndrome is characterized by formed visual
      hallucinations in individuals with vision loss. It is reported that one in five
      older adults with vision loss suffer from Charles Bonnet syndrome and the
      suspected lack of awareness amongst family physicians may lead to misdiagnosis
      and inappropriate treatment. Objective: To assess Canadian family physicians'
      awareness of Charles Bonnet syndrome. Methods: We conducted a national perception
      and practices survey of family physicians across Canada to assess (i) the level
      of awareness of Charles Bonnet syndrome amongst family physicians; (ii) the
      frequency of family physicians' encounters with patients with visual
      hallucinations and (iii) management strategies and referral patterns for patients
      with Charles Bonnet syndrome presenting to family physicians. Results: Four
      hundred and ninety-nine family physicians across Canada answered at least one
      question on the survey. 54.7% indicated they were not at all aware and 19.7%
      indicated they were slightly aware of Charles Bonnet syndrome. 72.8% of
      physicians had patients present with visual hallucinations once a year or less
      often. The frequency of patients seen in practice with visual hallucinations is
      significantly associated with awareness by physicians of Charles Bonnet syndrome
      (beta = 0.501, t(388) = 5.59, P < 0.001). Of those who encountered patients with
      visual hallucinations, the majority of respondents (77.4%) provided counselling
      or education to the patient. Conclusion: There is a great lack of knowledge about
      Charles Bonnet syndrome among family physicians. Awareness of Charles Bonnet
      syndrome is critical to appropriate diagnosis, assessment and treatment of this
      condition and to reassure patients that they are not suffering from a mental
      disorder.

PMID- 29471319
TI  - The Power of Beauty.

PMID- 29471320
TI  - Cover Crop Species and Management Influence Predatory Arthropods and Predation in
      an Organically Managed, Reduced-Tillage Cropping System.
AB  - Agricultural practices affect arthropod communities and, therefore, have the
      potential to influence the activities of arthropods. We evaluated the effect of
      cover crop species and termination timing on the activity of ground-dwelling
      predatory arthropods in a corn-soybean-wheat rotation in transition to organic
      production in Pennsylvania, United States. We compared two cover crop treatments:
      1) hairy vetch (Vicia villosa Roth) planted together with triticale
      (*Triticosecale Wittmack) after wheat harvest, and 2) cereal rye (Secale cereale
      Linnaeus) planted after corn harvest. We terminated the cover crops in the spring
      with a roller-crimper on three dates (early, middle, and late) based on cover
      crop phenology and standard practices for cash crop planting in our area. We
      characterized the ground-dwelling arthropod community using pitfall traps and
      assessed relative predation using sentinel assays with live greater waxworm
      larvae (Galleria mellonella Fabricius). The activity density of predatory
      arthropods was significantly higher in the hairy vetch and triticale treatments
      than in cereal rye treatments. Hairy vetch and triticale favored the predator
      groups Araneae, Opiliones, Staphylinidae, and Carabidae. Specific taxa were
      associated with cover crop condition (e.g., live or dead) and termination dates.
      Certain variables were positively or negatively associated with the relative
      predation on sentinel prey, depending on cover crop treatment and stage,
      including the presence of predatory arthropods and various habitat measurements.
      Our results suggest that management of a cover crop by roller-crimper at specific
      times in the growing season affects predator activity density and community
      composition. Terminating cover crops with a roller-crimper can conserve
      generalist predators.

PMID- 29471321
TI  - Overexpression of heparanase in mice promoted megakaryopoiesis.
AB  - Heparanase, an endo-glucuronidase that specifically cleaves heparan sulfate (HS),
      is upregulated in several pathological conditions. In this study, we aimed to
      find a correlation of heparanase expression and platelets production. In the
      transgenic mice overexpressing human heparanase (Hpa-tg), hematological analysis
      of blood samples revealed a significantly higher number of platelets in
      comparison with wild-type (Ctr) mice, while no significant difference was found
      in leukocytes and red blood cell number between the two groups. Total number of
      thiazole orange positive platelets was increased in Hpa-tg vs. Ctr blood,
      reflecting a higher rate of platelets production. Concomitantly, megakaryocytes
      from Hpa-tg mice produced more and shorter HS fragments that were shed into the
      medium. Further, thrombopoietin (TPO) level was elevated in the liver and plasma
      of Hpa-tg mice. Together, the data indicate that heparanase expression promoted
      megakaryopoiesis, which may be through upregulated expression of TPO and direct
      effect of released HS fragments expressed in the megakaryocytes.

PMID- 29471322
TI  - Whole-body nitrogen utilization and tissue protein and casein synthesis in
      lactating primiparous sows fed low- and high-protein diets.
AB  - Twenty-eight lactating Yorkshire and Yorkshire * Landrace primiparous sows were
      used to test the hypothesis that feeding a diet with reduced CP concentration and
      supplemented with crystalline AA (CAA) does not decrease milk protein yield and
      litter growth but improves apparent N utilization for milk protein production.
      Sows were assigned to 1 of 2 dietary treatments: 1) control (CON; 16.2% CP;
      analyzed content) or 2) low CP with CAA to meet estimated requirements of
      limiting AA (LCP; 12.7% CP) over a 17-d lactation period. A N balance was
      conducted for each sow between days 13 and 17 of lactation. On day 17, a 12-h
      primed continuous infusion of l-[ring-2H5]-Phe was conducted on 12 sows (n = 6)
      with serial blood and milk sampling to determine plasma AA concentrations and Phe
      enrichment, and milk casein synthesis, respectively. Thereafter, sows were
      sacrificed and tissues were collected to determine tissue protein fractional
      synthesis rates (FSR). Litter growth rate and milk composition did not differ.
      Sows fed the LCP diet had reduced N intake (122.7 vs. 153.2 g/d; P < 0.001) and
      maternal N retention (13.5 vs. 24.6 g/d; P < 0.05) and greater apparent
      efficiency of using dietary N intake for milk production (85.1% vs. 67.5%; P <
      0.001). On day 17 of lactation, all plasma essential AA concentrations exhibited
      a quartic relationship over time relative to consumption of a meal, where peaks
      occurred at approximately 1- and 4-h postprandial (P < 0.05). Protein FSR in
      liver, LM, gastrocnemius muscle, mammary gland, and in milk caseins did not
      differ between treatments. Feeding primiparous sows with a diet containing 12.7%
      CP and supplemented with CAA to meet the limiting AA requirements did not reduce
      milk protein yield or piglet growth rate and increased the apparent utilization
      of dietary N, Arg, Leu, Phe+Tyr, and Trp for milk protein production. The
      improved apparent utilization of N and AA appears to be related exclusively to a
      reduction in N and AA intake.

PMID- 29471323
TI  - What's to Be Done About Laboratory Quality? Process Indicators, Laboratory
      Stewardship, the Outcomes Problem, Risk Assessment, and Economic Value:
      Responding to Contemporary Global Challenges.
AB  - Objectives: For 50 years, structure, process, and outcomes measures have assessed
      health care quality. For clinical laboratories, structural quality has generally
      been assessed by inspection. For assessing process, quality indicators (QIs),
      statistical monitors of steps in the clinical laboratory total testing, have
      proliferated across the globe. Connections between structural and process
      laboratory measures and patient outcomes, however, have rarely been demonstrated.
      Methods: To inform further development of clinical laboratory quality systems, we
      conducted a selective but worldwide review of publications on clinical laboratory
      quality assessment. Results: Some QIs, like seven generic College of American
      Pathologists Q-Tracks monitors, have demonstrated significant process
      improvement; other measures have uncovered critical opportunities to improve test
      selection and result management. The College of Pathologists of Australasia Key
      Indicator Monitoring and Management System has deployed risk calculations,
      introduced from failure mode effects analysis, as surrogate measures for
      outcomes. Showing economic value from clinical laboratory testing quality is a
      challenge. Conclusions: Clinical laboratories should converge on fewer (7-14)
      rather than more (21-35) process monitors; monitors should cover all steps of the
      testing process under laboratory control and include especially high-risk
      specimen-quality QIs. Clinical laboratory stewardship, the combination of
      education interventions among clinician test orderers and report consumers with
      revision of test order formats and result reporting schemes, improves test
      ordering, but improving result reception is more difficult. Risk calculation
      reorders the importance of quality monitors by balancing three probabilities:
      defect frequency, weight of potential harm, and detection difficulty. The triple
      approach of (1) a more focused suite of generic consensus quality indicators, (2)
      more active clinical laboratory testing stewardship, and (3) integration of
      formal risk assessment, rather than competing with economic value, enhances it.

PMID- 29471325
TI  - Dual Stain With SATB2 and CK20/Villin Is Useful to Distinguish Colorectal
      Carcinomas From Other Tumors.
AB  - Objectives: Small sample size limits the number of immunostains that may be
      attempted in colorectal carcinoma (CRC) biopsy specimens. We investigated the
      utility of dual stain with special AT-rich sequence binding protein 2 (SATB2) or
      caudal-type homeobox 2 (CDX2) and cytokeratin 20 (CK20) or villin in identifying
      CRC. Methods: Tissue microarrays with 222 CRCs and 375 other carcinomas were
      built. Dual stain was performed pairing nuclear stains CDX2 or SATB2 with CK20 or
      villin. Results: All four single stains showed excellent sensitivity (93%-99%)
      but variable specificity (56%-88%) for CRC. All four dual stains also showed
      excellent sensitivity (90%-96%) while much improved specificity (88%-98%)
      compared with single stains. SATB2 dual stain (with CK20 or villin) showed a
      higher specificity than CDX2 dual stain (with CK20 or villin) with a comparable
      sensitivity. Conclusions: SATB2 dual stain shows the greatest potential clinical
      utility in identifying CRC and is superior to CDX2 dual stain. More important,
      SATB2 dual stain could be helpful for specimens with limited tissues or those
      having a nonclassic staining pattern.

PMID- 29471324
TI  - Effectiveness of Practices to Support Appropriate Laboratory Test Utilization: A
      Laboratory Medicine Best Practices Systematic Review and Meta-Analysis.
AB  - Objectives: To evaluate the effectiveness of practices used to support
      appropriate clinical laboratory test utilization. Methods: This review followed
      the Centers for Disease Control and Prevention (CDC) Laboratory Medicine Best
      Practices A6 cycle method. Eligible studies assessed one of the following
      practices for effect on outcomes relating to over- or underutilization:
      computerized provider order entry (CPOE), clinical decision support systems/tools
      (CDSS/CDST), education, feedback, test review, reflex testing, laboratory test
      utilization (LTU) teams, and any combination of these practices. Eligible
      outcomes included intermediate, systems outcomes (eg, number of tests
      ordered/performed and cost of tests), as well as patient-related outcomes (eg,
      length of hospital stay, readmission rates, morbidity, and mortality). Results:
      Eighty-three studies met inclusion criteria. Fifty-one of these studies could be
      meta-analyzed. Strength of evidence ratings for each practice ranged from high to
      insufficient. Conclusion: Practice recommendations are made for CPOE
      (specifically, modifications to existing CPOE), reflex testing, and combined
      practices. No recommendation for or against could be made for CDSS/CDST,
      education, feedback, test review, and LTU. Findings from this review serve to
      inform guidance for future studies.

PMID- 29471326
TI  - Urinary Cytomegalovirus Shedding in the United States: The National Health and
      Nutrition Examination Surveys, 1999-2004.
AB  - Background: There are no data on the prevalence of cytomegalovirus (CMV) shedding
      from a representative sample of the US population. This information is critical
      for understanding and preventing CMV. Methods: We tested urine specimens from CMV
      immunoglobulin (Ig) G-positive participants aged 6-49 years in 3 racial/ethnic
      groups from the National Health and Nutrition Examination Surveys 1999-2004 for
      the presence of CMV DNA using real-time polymerase chain reaction assay. We
      examined the association of sociodemographic characteristics with shedding
      prevalence and viral loads. Results: Among 6828 CMV IgG-positive participants
      tested, 537 had CMV DNA detected in urine-a shedding prevalence of 9.70%. Among
      persons aged 6-49 years, shedding prevalence was 3.83%. The prevalence of urinary
      shedding was inversely associated with increasing age (26.60%, 6.50%, and 3.45%
      in CMV IgG-positive participants aged 6-11, 12-19, and 20-49 years, respectively;
      P < .001 for trend test and pairwise comparisons). Urinary viral load also
      decreased significantly with age (mean, 2.97, 2.69, and 2.43 log10 copies/mL in
      those age groups, respectively; P < .001 for trend test and pairwise
      comparisons). Conclusions: Urinary CMV shedding and viral loads decreased
      dramatically with age, likely reflecting higher rates of primary CMV infection
      and longer duration of shedding in younger individuals. The findings demonstrate
      that children aged 6-11 years continue to shed CMV at higher rates and viral
      loads than adolescents and adults and thus may still be an important source for
      CMV transmission.

PMID- 29471327
TI  - Alachlor Use and Cancer Incidence in the Agricultural Health Study: An Updated
      Analysis.
AB  - Background: The herbicide alachlor has been widely used in US agriculture since
      its introduction in 1969. Experimental animal studies show that alachlor causes
      tumors in vivo; however, few epidemiologic studies have examined associations
      with human cancer risk. We evaluated alachlor use and cancer incidence in the
      Agricultural Health Study, updating an earlier analysis that suggested
      associations with lymphohematopoietic cancers with an additional 540 142 person
      years of follow-up and 5113 cancer cases. Methods: Pesticide applicators in Iowa
      and North Carolina reported lifetime alachlor use at enrollment (1993-1997) and
      follow-up (1999-2005). Exposure was characterized by cumulative intensity
      weighted days. We estimated relative risks (RRs) and 95% confidence intervals
      (CIs) using Poisson regression for incident cancers from enrollment through
      2012(NC)/2013(IA). Models adjusted for age, tobacco, alcohol, and other
      pesticides. All statistical tests are two-sided. Results: Among 49 685
      applicators, 25 640 (51.6%) used alachlor, with 3534 alachlor-exposed cancers.
      The relative risks of laryngeal cancer (nexposed = 34) increased in the second
      (RR = 4.68, 95% CI = 1.95 to 11.23), third (RR = 6.04, 95% CI = 2.44 to 14.99),
      and fourth quartiles (RR = 7.10, 95% CI = 2.58 to 19.53) of intensity-weighted
      days of use compared with no use (Ptrend = .001). Risk of myeloid leukemia was
      elevated, though not statistically significantly so, in the fourth quartile of
      intensity-weighted days of use (RR = 1.82, 95% CI = 0.85 to 3.87, Ptrend = .17).
      Conclusions: We observed a strong positive association with use of alachlor and
      laryngeal cancer and a weaker association with myeloid leukemia. The strength and
      robustness of the association with laryngeal cancer suggests that long-term
      occupational exposure to alachlor may be a risk factor for laryngeal cancer. This
      first report requires confirmation.

PMID- 29471328
TI  - A member of the Roseobacter clade, Octadecabacter sp., is the dominant symbiont
      in the brittle star Amphipholis squamata.
AB  - Symbiotic associations with subcuticular bacteria (SCB) have been identified and
      studied in many echinoderms, including the SCB of the brooding brittle star,
      Amphipholis squamata. Previous studies on the SCB of A. squamata placed the
      isolated bacterium, designated as AS1, in the genus Vibrio (Gammaproteobacteria),
      but subsequent studies suggested that the SCB of echinoderms belong to the
      Alphaproteobacteria. This study examines the taxonomic composition of SCB
      associated with A. squamata from the Northwest Atlantic using the 16S rRNA gene
      and next generation sequencing. Results show the presence of a single dominant
      bacterial type, within the Roseobacter clade, family Rhodobacteraceae, which
      composes 70%-80% of the A. squamata microbiome. These Rhodobacteraceae sequences
      were identified as members of the genus Octadecabacter. Additionally, the
      original isolate, AS1, from the brittle star A. squamata also belongs in the
      genus Octadecabacter based on Sanger sequencing of cloned 16S rRNA gene
      sequences. By comparison, adjacent seawater and sediment porewater communities
      were significantly more diverse, hosting bacteria in the phyla Proteobacteria,
      Bacteroidetes, Cyanobacteria, Verrucomicrobia and Actinobacteria. Thus, a
      distinct SCB community is present in A. squamata that is dominated by a member of
      the genus Octadecabacter and is identical to the original isolate, AS1, from this
      brittle star.

PMID- 29471329
TI  - Effects of Varenicline, Depressive Symptoms, and Region of Enrollment on Smoking
      Cessation in Depressed Smokers.
AB  - Introduction: Despite effective treatments, relapse to smoking remains a vexing
      global health problem. One predictor of relapse is depressive symptoms.
      Medications such as varenicline reduce withdrawal-related symptoms of depression,
      reducing relapse. This study examined whether varenicline moderated the effect of
      depressive symptoms on relapse, and whether this varied by region of enrollment.
      Methods: Adult smokers (n=525; 37% male) with past or current, stable major
      depressive disorder recruited from US (n=255), and European (n=270) sites
      participated in a randomized, double-blind cessation treatment trial including 12
      weeks of varenicline or placebo, with 40-week non-treatment follow-up. Results:
      Longitudinal and binary logistic regression were used to model the probability of
      sustained abstinence by end of treatment and point-prevalence abstinence in
      follow-up. The association between depression symptoms and abstinence was
      moderated by intervention group at end of treatment, and by region during follow
      up: more severe symptoms were associated with end-of-treatment relapse for
      placebo (OR = 0.91, p=.003), but not varenicline (OR = 0.99, p = .568). During
      follow-up, increased symptoms of depression predicted greater likelihood of
      smoking for European (p=.009) but not US participants. Europeans were more likely
      to be abstinent for both outcomes (p<.01). Conclusions: These results extend
      studies demonstrating varenicline is associated with less withdrawal-related
      depression, and suggest it aids cessation even in smokers with depressive
      symptoms. Findings also suggest regional differences in the relationship between
      depressive symptoms and cessation that may be related to differences in
      prevalence. Implications: This study indicates varenicline may aid cessation
      partially by reducing withdrawal-related symptoms of depression. It also suggests
      that the impact of depressive symptoms on cessation varies regionally, and that
      this variation may be related to differences in smoking prevalence.

PMID- 29471330
TI  - Converging and diverging needs between patients and providers who are collecting
      and using patient-generated health data: an integrative review.
AB  - Objective: This integrative review identifies convergent and divergent areas of
      need for collecting and using patient-generated health data (PGHD) identified by
      patients and providers (i.e., physicians, nurses, advanced practice nurses,
      physician assistants, and dietitians). Methods: A systematic search of 9
      scholarly databases targeted peer-reviewed studies published after 2010 that
      reported patients' and/or providers' needs for incorporating PGHD in clinical
      care. The studies were assessed for quality and bias with the Mixed-Methods
      Appraisal Tool. The results section of each article was coded to themes
      inductively developed to categorize patient and provider needs. Distinct claims
      were extracted and areas of convergence and divergence identified. Results:
      Eleven studies met inclusion criteria. All had moderate to low risk of bias.
      Three themes (clinical, logistic, and technological needs), and 13 subthemes
      emerged. Forty-eight claims were extracted. Four were divergent and twenty were
      convergent. The remainder was discussed by only patients or only providers.
      Conclusion: As momentum gains for integrating PGHD into clinical care, this
      analysis of primary source data is critical to understanding the requirements of
      the 2 groups directly involved in collection and use of PGHD.

PMID- 29471332
TI  - Mycobacterium tuberculosis-Infected Hematopoietic Stem and Progenitor Cells
      Unable to Express Inducible Nitric Oxide Synthase Propagate Tuberculosis in Mice.
AB  - Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has
      been identified as a potential bacterial niche during latent tuberculosis. Using
      a murine model of tuberculosis, we show here that bone marrow stem and progenitor
      cells containing M. tuberculosis propagated tuberculosis when transferred to
      naive mice, given that both transferred cells and recipient mice were unable to
      express inducible nitric oxide synthase, which mediates killing of intracellular
      bacteria via nitric oxide. Our findings suggest that bone marrow stem and
      progenitor cells containing M. tuberculosis propagate hallmarks of disease if
      nitric oxide-mediated killing of bacteria is defective.

PMID- 29471331
TI  - Cross Cultural Validation and Extension of the Clinical Assessment Interview for
      Negative Symptoms (CAINS) in the Chinese Context: Evidence from a Spectrum
      Perspective.
AB  - The Clinical Assessment Interview for Negative Symptoms (CAINS) was designed in
      accordance with the recent theory and research in social affective neuroscience
      and to address the psychometric and conceptual limitations of other instruments
      assessing negative symptoms. The present study aimed to provide a large-scale
      validation of the CAINS in China and examine its applicability and validity
      evidence across the schizophrenia spectrum. Using confirmatory factor analysis,
      our results replicated the original findings in the US development samples that
      the CAINS possesses a stable 2-factor structure, namely "motivation/pleasure" and
      "expression". We also found significant correlations between the CAINS and other
      negative symptom measures. The CAINS demonstrated good discriminant validity in
      differentiating negative symptoms in people with schizophrenia, nonpsychotic
      first-degree relatives and people with social anhedonia. People with
      schizophrenia exhibited significantly higher CAINS subscale scores than first
      degree relatives and healthy controls. In addition, first-degree relatives had
      higher "motivation/pleasure" scores than healthy controls. The
      "motivation/pleasure" subscale scores of individuals with social anhedonia were
      also significantly higher than healthy controls.

PMID- 29471333
TI  - Genomic dissection of enhancers uncovers principles of combinatorial regulation
      and cell type-specific wiring of enhancer-promoter contacts.

PMID- 29471334
TI  - Progress toward elimination of onchocerciasis in the Americas.
AB  - The Onchocerciasis Elimination Program for the Americas (OEPA) is a regional
      initiative and international partnership that has made considerable progress
      toward its goal since it was launched in 1993. Its strategy is based on mass drug
      administration of ivermectin (Mectizan, donated by MSD, also known as Merck &
      Co., Inc., Kenilworth, NJ, USA), twice or four times per year, with at least 85%
      coverage of eligible populations. From 1989 to 2016, 11 741 276 ivermectin
      treatments have been given in the Americas, eliminating transmission in 11 of 13
      foci. The OEPA's success has had a great influence on programs in Africa,
      especially Sudan and Uganda, which moved from a control to an elimination
      strategy in 2006 and 2007, respectively. The successes in the Americas have also
      greatly influenced WHO guidelines for onchocerciasis transmission elimination.
      With four of the six originally endemic American countries now WHO verified as
      having eliminated onchocerciasis transmission, and 95% of ivermectin treatments
      in the region halted, the regional focus is now on the remaining active
      transmission zone, called the Yanomami Area, on the border between Venezuela and
      Brazil. Both countries have difficult political climates that hinder the
      elimination task in this remote and relatively neglected region. As with other
      elimination efforts, 'the final inch' is often the most difficult task of all.

PMID- 29471335
TI  - After 70 years of fighting an age-old scourge, onchocerciasis in Uganda, the end
      is in sight.
AB  - Onchocerciasis causes severe itching, serious skin disease and ocular damage
      leading to visual impairment or permanent blindness. It is associated with
      hanging groin, epilepsy, Nakalanga dwarfism and, most recently, nodding disease.
      This disease affected communities in 17 transmission foci in 37 districts of
      Uganda, where about 6.7 million people are once at risk. The efforts against
      onchocerciasis in Uganda commenced in the late 1940s, when vector control was
      launched using dichlorodiphenyltrichloroethane; by 1973, Simulium damnosum had
      been eliminated in the Victoria focus. Success outside of the Victoria focus was
      short-lived due to changes in government priorities and the political upheavals
      of the 1970s and 1980s. With the return of political stability, annual treatment
      with ivermectin through mass drug administration was launched in the early 1990s.
      Control of the disease has been successful, but there has been failure in
      interrupting transmission after more than 15 years. In 2007 Uganda launched a
      nationwide transmission elimination policy based on twice-per-year treatment and
      vector control/elimination, with a goal of eliminating river blindness nationwide
      by 2020. By 2017, 1 157 303 people from six foci had been freed from river
      blindness. This is the largest population ever declared free under World Health
      Organization elimination guidelines, providing evidence that elimination of river
      blindness in Africa is possible.

PMID- 29471336
TI  - Diagnostics for onchocerciasis in the era of elimination.
AB  - In the past few years, efforts to eliminate onchocerciasis from Africa have
      intensified. These efforts are primarily based on the mass distribution of the
      anti-helminthic drug MectizanTM (ivermectin). This program has led to the
      development of new guidelines by the World Health Organization for the
      verification that transmission has been suppressed and eventually eliminated. The
      requirements of diagnostic tools for this purpose differ in many ways from tests
      used to diagnose infection in individuals. In this review, we summarize the
      progress that has been made to identify diagnostics that meet the specialized
      requirements needed to verify onchocerciasis elimination, discuss why these tests
      were selected and summarize the needs that still exist to complete the arsenal of
      diagnostic tools that will be useful as the goal of elimination is achieved.

PMID- 29471337
TI  - The role of national committees in eliminating onchocerciasis.
AB  - National onchocerciasis elimination committees (NOECs) serve to help ministries
      of health complete the pathway to successful verification of elimination of
      onchocerciasis (river blindness), as outlined in the 2016 World Health
      Organization guidelines. These guidelines, however, only take effect when the
      country believes it has reached a point that elimination can be demonstrated, and
      do not address the preceding milestones. Therefore, NOECs can be of great help
      with guiding and tailoring earlier planning, programming and assessments to
      empower national programs to aggressively move toward their countries'
      elimination goals. In this article, we provide suggestions for organizing NOECs
      and examples of four such committees that have successfully operated in Africa
      and the Americas.

PMID- 29471338
TI  - Transitioning from river blindness control to elimination: steps toward stopping
      treatment.
AB  - The transition from onchocerciasis control to elimination requires country
      programmes to rethink their approach to a variety of activities as they move from
      addressing morbidity to addressing transmission of the parasite. Although the
      2016 WHO guidelines provide extensive recommendations, it was beyond the scope of
      the document to provide guidance on all aspects of the transition. This paper
      will discuss some of the important issues that programmes are grappling with as
      they transition to elimination and provide some potential approaches that
      programmes can use to address them. Although there are some data to support some
      aspects of the suggested approaches, operational research will be needed to
      generate data to support these approaches further and to determine how programmes
      could best tailor them to their own unique epidemiological challenges. Good
      communication between the national programmes and the broader global programme
      will facilitate the clear articulation of programmatic challenges and the
      development of the evidence to support programme decision-making.

PMID- 29471339
TI  - The role of the NGDO Coordination Group for the Elimination of Onchocerciasis.
AB  - The NGDO Coordination Group for the Control of Onchocerciasis was launched in
      1992, and with the paradigm shift from control of disease to elimination of
      onchocerciasis transmission, the Group shifted its orientation to that new
      paradigm in 2013. It also changed its name, replacing 'control' with
      'elimination.' In doing so, the Group has repositioned itself to build on the
      successes of the past to finish the job it began over 25 years ago.

PMID- 29471340
TI  - Operationalization of the test and not treat strategy to accelerate the
      elimination of onchocerciasis and lymphatic filariasis in Central Africa.
AB  - After 30 years of treatment with Mectizan (ivermectin), cutaneous and ocular
      complications of Onchocerca volvulus infection are now scarce in endemic
      communities. Indeed, transmission has been interrupted and the O. volvulus-
      associated disease has disappeared in some African foci. Despite this success,
      onchocerciasis elimination in Loa loa co-endemic areas is still constrained by
      severe adverse events (SAEs) occurring after ivermectin treatment in some
      individuals harbouring very high L. loa microfilaremia. One approach towards the
      prevention of these SAEs is to identify individuals with high L. loa
      microfilaremia and exclude them from ivermectin treatment. The development of the
      LoaScope has provided the tool that underlies this test and not treat (TaNT)
      strategy. The first successful TaNT campaign was conducted in a L. loa highly
      endemic focus in Cameroon in 2015 without any SAEs. To accomplish this within a
      research setting, 60 people were deployed for this campaign, making this
      'research' strategy not sustainable from a cost perspective. We describe here a
      way of reducing the cost of the TaNT strategy with a smaller team (three people)
      selected within affected communities. We also suggest the organization of a TaNT
      campaign in affected countries.

PMID- 29471341
TI  - Onchocerciasis: shifting the target from control to elimination requires a new
      first-step-elimination mapping.
AB  - The meaning of 'mapping' in relation to onchocerciasis has changed at least three
      times over the past 50 years as the programmatic goals and the assessment tools
      have changed. With the current goal being global elimination of Onchocerca
      volvulus (OV), all areas where OV might currently be transmitted and where mass
      drug administration (MDA) with ivermectin treatment has not been delivered
      previously must now be identified by careful, detailed 'elimination mapping' as
      either OV endemic or not, so that appropriate programmatic targets can be
      established. New tools and strategies for such elimination mapping have become
      available, though ongoing studies must still be completed to define agreed upon
      optimal diagnostic evaluation units, sampling strategies and serologic tools.
      With detailed guidance and technical support from the World Health Organization
      and with implementation and financial support from their global partners, the OV
      endemic countries of Africa can soon complete their elimination mapping and then
      continue with MDA programmes to progressively achieve the same success in OV
      elimination as that already achieved by the growing list of formerly OV-endemic
      countries in the Americas.

PMID- 29471343
TI  - Onchocerciasis in Yemen: moving forward towards an elimination program.
AB  - The onchocerciasis focus in Yemen has been known for many years as an endemic
      area with unique characteristics, notably the atypical and most severe form of
      onchodermatitis, known as sowda or reactive onchodermatitis (ROD). The national
      effort to control the disease began in 1992 as an individual case treatment
      program by administering ivermectin to those presenting with ROD. The challenging
      geography of the endemic area and the current political and military unrest both
      underscore a need for special approaches when attempting to eliminate
      onchocerciasis from this country. An assessment of the national situation
      regarding this disease was carried out in 2011-2013 aimed at defining the best
      approach for moving from individual clinical case treatment to elimination of
      transmission. The history of the control efforts and the current status of the
      disease are reviewed and the essential changes needed to a mass drug
      administration (MDA) approach are identified as the national program addresses
      elimination. Yemen, despite the current troubles, has shown that it can
      successfully implement MDA programs despite many difficulties and therefore
      should be supported in its efforts towards countrywide elimination of this
      infection; however, success will need renewed national and international efforts.

PMID- 29471342
TI  - Alternative treatment strategies to accelerate the elimination of onchocerciasis.
AB  - The use of alternative (or complementary) treatment strategies (ATSs) i.e.
      differing from annual community-directed treatment with ivermectin (CDTI) is
      required in some African foci to eliminate onchocerciasis by 2025. ATSs include
      vector control, biannual or pluriannual CDTI, better timing of CDTI, community
      directed treatment with combinations of currently available anthelminthics or new
      drugs, and 'test-and-treat' (TNT) strategies requiring diagnosis of infection
      and/or contraindications to treatment for decisions on who to treat with what
      regimen. Two TNT strategies can be considered. Loa-first TNT, designed for
      loiasis-endemic areas and currently being evaluated using a rapid test
      (LoaScope), consists of identifying individuals with levels of Loa microfilaremia
      associated with a risk of post-ivermectin severe adverse events to exclude them
      from ivermectin treatment and in treating the rest (usually >97%) of the
      population safely. Oncho-first TNT consists of testing community members for
      onchocerciasis before giving treatment (currently ivermectin or doxycycline) to
      those who are infected. The choice of the ATS depends on the prevalences and
      intensities of infection with Onchocerca volvulus and Loa loa and on the relative
      cost-effectiveness of the strategies for the given epidemiological situation.
      Modelling can help select the optimal strategies, but field evaluations to
      determine the relative cost-effectiveness are urgently needed.

PMID- 29471344
TI  - Cross-border issues: an important component of onchocerciasis elimination
      programmes.
AB  - Endemic areas that involve national or local borders present an important
      challenge to the success of elimination of onchocerciasis; such cross-border
      endemic foci require special attention to ensure that programme activities are
      unified. It is vital that national programmes and the committees responsible for
      the oversight of progress towards elimination are aware and address such issues
      in their current planning and programmatic activities. Although international
      borders that intersect endemic zones present the biggest challenge, intracountry
      borders (such as between administrative districts or loiasis endemic and non
      loiasis areas) can also pose problems. The recent change in the onchocerciasis
      programme from disease control to transmission interruption, given the historical
      lack of treatment in hypo-endemic areas, may have increased the already
      relatively high number of cross-national scenarios in Africa. It is vital that
      all national programmes address the issue of any cross-border endemic areas as a
      matter of urgency and include this important issue in their elimination plans.

PMID- 29471345
TI  - Establishing quality assured (QA) laboratory support for onchocerciasis
      elimination in Africa.
AB  - An essential component in achieving accepted successful elimination of a disease
      or a pathogen involves the acquisition of quality-assured (QA) data that
      ultimately define the absence of infection or transmission in previously endemic
      areas. The acquisition of these essential data, in the case of onchocerciasis
      elimination, requires strong laboratory support for both testing and continuing
      evaluation/validation of the tools used for the required diagnostic and
      epidemiology procedures. There is also a need for standardization of the
      laboratory-based and field-based assays used across the onchocerciasis-endemic
      countries as well as continuing technical, fiscal and logistical support for
      laboratory activities. To achieve these needs, it is proposed to build on the
      existing onchocerciasis programme laboratory activities in the endemic areas by
      expanding these to include additional laboratories as referral services organized
      on a regional basis to support the needs of endemic countries. Included in these
      plans are the development of quality assurance mechanisms, supply chain
      procedures and standardization of protocols for the basic assays needed for both
      national onchocerciasis elimination programme surveys and supporting research
      activities. Such an entity could then include quality-assured testing for other
      neglected tropical diseases.

PMID- 29471346
TI  - Refocusing vector assessment towards the elimination of onchocerciasis from
      Africa: a review of the current status in selected countries.
AB  - Measures to control onchocerciasis have been in place for well over 30 years.
      Recently, programs have turned from disease control towards transmission
      elimination. The absence of infective larvae in the black fly Simulium sp. vector
      is central to defining elimination, and assessments of infectivity by O150
      polymerase chain reaction in the vector not only provide valuable information to
      programs, but are also required for verification of elimination. The status of
      transmission in black flies was assessed in five countries in the African region
      during 2014 and 2015. Several of these countries were evaluated because of
      promising results from epidemiological studies in humans. No infective flies were
      found in two countries. Infective flies were found in the other three, despite
      the absence of infection in humans (as evaluated by skin-snip microscopy).
      Ongoing transmission as demonstrated in the black flies could be due to a variety
      of factors, including lack of treatment of hypo-endemic areas and cross-border
      issues. Challenges identified during the course of the entomological work suggest
      that there is a need for improved selection of vector collection sites and vector
      collection periods in order to improve fly catches. Two important challenges to
      achieving elimination identified were definition of the hypo-endemic zones and
      establishing the existence of areas of cross-border transmission occurring
      between countries.

PMID- 29471347
TI  - Onchocerciasis: the beginning of the end.

PMID- 29471348
TI  - Sexual Dimorphism of Resting-State Network Connectivity in Healthy Ageing.
AB  - Objectives: The onset of many illnesses is confounded with age and sex.
      Increasing age is a risk factor for the development of many illnesses, and sexual
      dimorphism influences brain anatomy, function, and cognition. Here, we examine
      frequency-specific connectivity in resting-state networks in a large sample (n =
      406) of healthy aged adults. Method: We quantify frequency-specific connectivity
      in three resting-state networks known to be implicated in age-related decline:
      the default mode, dorsal attention, and salience networks, using multiband
      functional magnetic resonance imaging. Frequency-specific connectivity was
      quantified in four bands: low (0.015-0.027 Hz), moderately low (0.027-0.073 Hz),
      moderately high (0.073-0.198 Hz), and high (0.198-0.5 Hz) frequency bands, using
      mean intensity and spatial extent. Differences in connectivity between the sexes
      in each of the three networks were examined. Results: Each network showed the
      largest intensity and spatial extent at low frequencies and smallest extent at
      high frequencies. Males showed greater connectivity than females in the salience
      network. Females showed greater connectivity than males in the default mode
      network. Discussion: Results in this healthy aged cohort are compatible with
      those obtained in young samples, suggesting that frequency-specific connectivity,
      and differences between the sexes, are maintained into older age. Our results
      indicate that sex should be considered as an influencing factor in studies of
      resting-state connectivity.

PMID- 29471349
TI  - Intestinal Colonization Traits of Pandemic Multidrug-Resistant Escherichia coli
      ST131.
AB  - Background: Epidemiological studies point to the gut as a key reservoir of
      multidrug resistant Escherichia coli multilocus sequence type 131 (ST131), a
      globally dominant pathogenic clone causing urinary tract and bloodstream
      infections. Here we report a detailed investigation of its intestinal lifestyle.
      Methods: Clinical ST131 isolates and type 1 fimbriae null mutants were assessed
      for colonization of human intestinal epithelia and in mouse intestinal
      colonization models. Mouse gut tissue underwent histologic analysis for pathology
      and ST131 localization. Key findings were corroborated in mucus-producing human
      cell lines and intestinal biopsy specimens. Results: ST131 strains adhered to and
      invaded human intestinal epithelial cells more than probiotic and commensal
      strains. The reference ST131 strain EC958 established persistent intestinal
      colonization in mice, and expression of type 1 fimbriae mediated higher
      colonization levels. Bacterial loads were highest in the distal parts of the
      mouse intestine and did not cause any obvious pathology. Further analysis
      revealed that EC958 could bind to both mucus and underlying human intestinal
      epithelia. Conclusions: ST131 strains can efficiently colonize the mammalian gut
      and persist long term. Type 1 fimbriae enhance ST131 intestinal colonization,
      suggesting that mannosides, currently developed as therapeutics for bladder
      infections and Crohn's disease, could also be used to limit intestinal ST131
      reservoirs.

PMID- 29471350
TI  - Structural and mechanistic insights into UHRF1-mediated DNMT1 activation in the
      maintenance DNA methylation.
AB  - UHRF1 plays multiple roles in regulating DNMT1-mediated DNA methylation
      maintenance during DNA replication. The UHRF1 C-terminal RING finger functions as
      an ubiquitin E3 ligase to establish histone H3 ubiquitination at Lys18 and/or
      Lys23, which is subsequently recognized by DNMT1 to promote its localization onto
      replication foci. Here, we present the crystal structure of DNMT1 RFTS domain in
      complex with ubiquitin and highlight a unique ubiquitin binding mode for the RFTS
      domain. We provide evidence that UHRF1 N-terminal ubiquitin-like domain (UBL)
      also binds directly to DNMT1. Despite sharing a high degree of structural
      similarity, UHRF1 UBL and ubiquitin bind to DNMT1 in a very distinct fashion and
      exert different impacts on DNMT1 enzymatic activity. We further show that the
      UHRF1 UBL-mediated interaction between UHRF1 and DNMT1, and the binding of DNMT1
      to ubiquitinated histone H3 that is catalyzed by UHRF1 RING domain are critical
      for the proper subnuclear localization of DNMT1 and maintenance of DNA
      methylation. Collectively, our study adds another layer of complexity to the
      regulatory mechanism of DNMT1 activation by UHRF1 and supports that individual
      domains of UHRF1 participate and act in concert to maintain DNA methylation
      patterns.

PMID- 29471351
TI  - Viability of Campylobacter spp. in frozen and chilled broiler carcasses according
      to real-time PCR with propidium monoazide pretreatment.
AB  - The aim of this study was to evaluate the viability of Campylobacter spp. in
      frozen and chilled broiler carcasses using real-time PCR with propidium monoazide
      (PMA) pretreatment. Sixty broiler carcasses were collected: 30 frozen and 30
      chilled. Each carcass was submitted to 2 real-time PCR protocols to detect and
      quantify Campylobacter spp.: one using pretreatment with PMA, which blocks the
      amplification of DNA from dead bacteria, and the other without PMA. The results
      showed that PMA-pretreated carcasses, either frozen or chilled, had a lower
      positivity rate compared to untreated samples (P < 0.001). Regarding storage
      temperatures, PMA-pretreated frozen carcasses that tested positive were in a
      lesser number than chilled carcasses (P < 0.05). However, the quantification of
      total and live bacteria in PMA-pretreated frozen carcasses that tested positive
      showed no significant difference compared to chilled carcasses. It was concluded
      that the real-time PCR with PMA pretreatment was a sensitive method for
      evaluating the viability of Campylobacter spp. in broiler carcasses. Chilled
      broiler carcasses would represent greater hazard to public health concerning
      Campylobacter transmission.

PMID- 29471352
TI  - Delay to Formalin Fixation (Cold Ischemia Time) Effect on Breast Cancer
      Molecules.
AB  - Objectives: The gold standard of examining breast biomarkers, including estrogen
      receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2
      (HER2)/Ki-67, is to perform these assays on formalin-fixed, paraffin-embedded
      tissue. However, preanalytical variables may confound these assays. One of these
      factors is delay to formalin fixation (DFF). The purpose of this review is to
      evaluate each study that investigated the effect of DFF on breast biomarkers and
      other molecules. Methods: Thirteen primary research articles were identified by
      the literature search. The credibility of the studies was judged based on the
      degree of controlling other confounding factors. Nine studies had a prospective
      design with a high number of controlled variables. Results: Most of the studies
      concluded that DFF had an effect on ER/PR/HER2. Some of these studies showed that
      DFF had negative effect on other markers used either clinically or for research
      purposes. Conclusions: The vast majority of the studies agree that DFF has
      negative effect on breast biomarkers.

PMID- 29471353
TI  - Spleen Registry: Still a Chimera.

PMID- 29471354
TI  - A coliform-targeted metagenomic method facilitating human exposure estimates to
      Escherichia coli-borne antibiotic resistance genes.
AB  - Antimicrobial resistance and the spread of antibiotic resistance genes (ARGs)
      pose a threat to human health. Community-acquired infections resistant to
      treatment with first-line antibiotics are increasing, and there are few studies
      investigating environmental exposures and transmission. Our objective is to
      develop a novel targeted metagenomic method to quantify the abundance and
      diversity of ARGs in a faecal indicator bacterium, and to estimate human exposure
      to resistant bacteria in a natural environment. Sequence data from Escherichia
      coli metagenomes from 13 bathing waters in England were analysed using the ARGs
      Online Analysis Pipeline to estimate the abundance and diversity of resistance
      determinants borne by this indicator bacterium. These data were averaged over the
      13 sites and used along with data on the levels of E. coli in English bathing
      waters in 2016 and estimates of the volume of water that water users typically
      ingest in an average session of their chosen activityto quantify the numbers of
      ARGs that water users ingest. Escherichia coli in coastal bathing waters were
      found to harbour on average 1.24 ARGs per cell. Approximately 2.5 million water
      sports sessions occurred in England in 2016 that resulted in water users
      ingesting at least 100 E. coli-borne ARGs.

PMID- 29471355
TI  - Closing the loop with an enhanced referral management system.
AB  - Objective: To evaluate the impact of a referral manager tool on primary care
      practices. Materials and Methods: We evaluated a referral manager module in a
      locally developed electronic health record (EHR) that was enhanced to improve the
      referral management process in primary care practices. Baseline (n = 61) and
      follow-up (n = 35) provider and staff surveys focused on the ease of performing
      various steps in the referral process, confidence in completing those steps, and
      user satisfaction. Additional metrics were calculated that focused on completed
      specialist visits, acknowledged notes, and patient communication. Results: Of
      1341 referrals that were initiated during the course of the study, 76.8% were
      completed. All the steps of the referral process were easier to accomplish
      following implementation of the enhanced referral manager module in the EHR.
      Specifically, tracking the status of an in-network referral became much easier
      (+1.43 [3.91-2.48] on a 5-point scale, P < .0001). Although we found improvement
      in the ease of performing out-of-network referrals, there was a greater impact on
      in-network referrals. Discussion: Implementation of an electronic tool developed
      using user-centered design principles along with adequate staff to monitor and
      intervene when necessary made it easier for primary care practices to track
      referrals and to identify if a breakdown in the process occurred. This is
      especially important for high-priority referrals. Out-of-network referrals
      continue to present challenges, which may eventually be helped by improving
      interoperability among EHRs and scheduling systems. Conclusion: An enhanced
      referral manager system can improve referral workflows, leading to enhanced
      efficiency and patient safety and reduced malpractice risk.

PMID- 29471356
TI  - Characterization of p57, a Stage-Specific Antigen of Pneumocystis murina.
AB  - Pneumocystis has a large multicopy gene family encoding proteins related to the
      major surface glycoprotein (Msg), whose functions are largely unknown. We
      expressed one such protein of Pneumocystis murina, p57, which is encoded by 3
      highly conserved genes, and demonstrated by immunoblot that immunocompetent mice
      that were immunized with crude Pneumocystis antigens or that had cleared
      Pneumocystis infection developed antibodies to p57. Using hyperimmune anti-p57
      serum combined with immunolabeling, we found that p57 was expressed by small
      trophic forms and intracystic bodies, whereas it was not expressed on larger
      trophic forms or externally by cysts. Expression of p57 and Msg by trophic forms
      was largely mutually exclusive. Treatment of infected animals with caspofungin
      inhibited cyst formation and markedly decreased p57 expression. While p57
      expression was seen in immunocompetent mice infected with Pneumocystis,
      immunization with recombinant p57 did not result in altered cytokine expression
      by lymphocytes or in diminished infection in such mice. Thus, p57 appears to be a
      stage-specific antigen of Pneumocystis that is expressed on intracystic bodies
      and young trophic forms and may represent a mechanism to conserve resources in
      organisms during periods of limited exposure to host immune responses.

PMID- 29471357
TI  - Obese Hypertensive Men Have Lower Circulating Proatrial Natriuretic Peptide
      Concentrations Despite Greater Left Atrial Size.
AB  - BACKGROUND: Obese persons have lower circulating natriuretic peptide (NP)
      concentrations. It has been proposed that this natriuretic handicap plays a role
      in obesity-related hypertension. In contrast, hypertensive patients with left
      atrial enlargement have higher circulating NP concentrations. On this background,
      we investigated whether obese hypertensive men could have lower circulating NP
      concentrations despite evidence of pressure-induced greater left atrial size.
      METHODS: We examined 98 obese men (body mass index [BMI] >= 30.0 kg/m2) and 27
      lean normotensive men (BMI 20.0-24.9 kg/m2). All men were healthy, medication
      free, with normal left ventricular ejection fraction. We measured blood pressure
      using 24-hour ambulatory blood pressure (ABP) recordings. Hypertension was
      defined as 24-hour ABP >= 130/80 mm Hg, and normotension was defined as 24-hour
      ABP < 130/80 mm Hg. We determined left atrial size using echocardiography, and we
      measured fasting serum concentrations of midregional proatrial NP (MR-proANP).
      RESULTS: Of the 98 obese men, 62 had hypertension and 36 were normotensive. The
      obese hypertensive men had greater left atrial size (mean +/- SD: 28.7 +/- 6.0
      ml/m2) compared with the lean normotensive men (23.5 +/- 4.5 ml/m2) and the obese
      normotensive men (22.7 +/- 5.1 ml/m2), P < 0.01. Nevertheless, despite evidence
      of pressure-induced greater left atrial size, the obese hypertensive men had
      lower serum MR-proANP concentrations (median [interquartile range]: 48.5 [37.0
      64.7] pmol/l) compared with the lean normotensive men (69.3 [54.3-82.9] pmol/l),
      P < 0.01, whereas the obese normotensive men had serum MR-proANP concentrations
      in between the 2 other groups (54.1 [43.6-62.9] pmol/l). CONCLUSIONS: Despite
      greater left atrial size, obese hypertensive men have lower circulating MR-proANP
      concentrations compared with lean normotensive men.

PMID- 29471358
TI  - eIF4A alleviates the translational repression mediated by classical secondary
      structures more than by G-quadruplexes.
AB  - Increased activity of the mRNA helicase eIF4A drives cellular malignancy by
      reprogramming cellular translation, and eIF4A activity is the direct or indirect
      target of many emerging cancer therapeutics. The enriched presence of (GGC)4
      motifs, which have the potential to fold into two-layered G-quadruplexes, within
      the 5'UTRs of eIF4A-dependent mRNAs suggests that eIF4A is required for the
      unwinding of these structures within these eIF4A-controlled mRNAs. However, the
      existence of folded G-quadruplexes within cells remains controversial, and G
      quadruplex folding is in direct competition with classical Watson-Crick based
      secondary structures. Using a combination of reverse transcription stalling
      assays and 7-deazaguanine incorporation experiments we find that (GGC)4 motifs
      preferentially form classical secondary structures rather than G-quadruplexes in
      full-length mRNAs. Furthermore, using translation assays with the eIF4A inhibitor
      hippuristanol, both in vitro and in cells, we find that eIF4A activity alleviates
      translational repression of mRNAs with 5'UTR classical secondary structures
      significantly more than those with folded G-quadruplexes. This was particularly
      evident in experiments using a G-quadruplex stabilizing ligand, where shifting
      the structural equilibrium in favour of G-quadruplex formation diminishes eIF4A
      dependency. This suggests that enrichment of (GGC)4 motifs in the 5'UTRs of eIF4A
      dependent mRNAs is due to the formation of stable hairpin structures rather than
      G-quadruplexes.

PMID- 29471360
TI  - Adverse Consequences of Unmet Needs for Care in High-Need/High-Cost Older Adults.
AB  - Objectives: We explore adverse consequences of unmet needs for care among high
      need/high-cost (HNHC) older adults. Method: Interviews with 4,024 community
      dwelling older adults with ADL/IADL/mobility disabilities from the 2011 National
      Health and Aging Trends Study (NHATS). Reports of socio-demographics, disability
      compensatory strategies, and adverse consequences of unmet needs in the past
      month were obtained from older adults with multiple chronic conditions (MCC),
      probable dementia (DEM), and/or near end-of-life (EOL) and compared older adults
      not meeting these criteria. Results: Older adults with MCC (31.6%), DEM (39.6%),
      and EOL (48.7%) reported significantly more adverse consequences than low-need
      older adults (21.4%). Persons with MCC & DEM (53.4%), MCC & EOL (53.2%), and all
      three (MCC, DEM, EOL, 65.6%) reported the highest levels of adverse consequences.
      HNHC participants reported more environmental modifications, assistive device,
      and larger helper networks. HNHC status independently predicted greater adverse
      consequences after controlling for disability compensatory strategies in
      multivariate models. Discussion: Adverse consequences of unmet needs for care are
      prevalent among HNHC older adults, especially those with multiple indicators,
      despite more disability-related compensatory efforts and larger helper networks.
      Helping caregivers provide better informal care has potential to contain
      healthcare costs by reducing hospitalization and unplanned readmissions.

PMID- 29471361
TI  - Microbial community composition along a 50 000-year lacustrine sediment sequence.
AB  - For decades, microbial community composition in subseafloor sediments has been
      the focus of extensive studies. In deep lacustrine sediments, however, the
      taxonomic composition of microbial communities remains undercharacterized.
      Greater knowledge on microbial diversity in lacustrine sediments would improve
      our understanding of how environmental factors, and resulting selective
      pressures, shape subsurface biospheres in marine and freshwater sediments. Using
      high-throughput sequencing of 16S rRNA genes across high-resolution climate
      intervals covering the last 50 000 years in Laguna Potrok Aike, Argentina, we
      identified changes in microbial populations in response to both past
      environmental conditions and geochemical changes of the sediment during burial.
      Microbial communities in Holocene sediments were most diverse, reflecting a
      layering of taxa linked to electron acceptors availability. In deeper intervals,
      the data show that salinity, organic matter and the depositional conditions over
      the Last Glacial-interglacial cycle were all selective pressures in the deep
      lacustrine assemblage resulting in a genetically distinct biosphere from the
      surface dominated primarily by Bathyarchaeota and Atribacteria groups. However,
      similar to marine sediments, some dominant taxa in the shallow subsurface
      persisted into the subsurface as minor fraction of the community. The subsequent
      establishment of a deep subsurface community likely results from a combination of
      paleoenvironmental factors that have shaped the pool of available substrates,
      together with substrate depletion and/or reworking of organic matter with depth.

PMID- 29471362
TI  - Changes in hospital bond ratings after the transition to a new electronic health
      record.
AB  - Objective: To assess the impact of electronic health record (EHR) implementation
      on hospital finances. Materials and Methods: We analyzed the impact of EHR
      implementation on bond ratings and net income from service to patients (NISP) at
      32 hospitals that recently implemented a new EHR and a set of controls. Results:
      After implementing an EHR, 7 hospitals had a bond downgrade, 7 had a bond
      upgrade, and 18 had no changes. There was no difference in the likelihood of bond
      rating changes or in changes to NISP following EHR go-live when compared to
      control hospitals. Discussion: Most hospitals in our analysis saw no change in
      bond ratings following EHR go-live, with no significant differences observed
      between EHR implementation and control hospitals. There was also no apparent
      difference in NISP. Conclusions: Implementation of an EHR did not appear to have
      an impact on bond ratings at the hospitals in our analysis.

PMID- 29471363
TI  - Proteome Analysis of a M. avium Mutant Exposes a Novel Role of the Bifunctional
      Protein LysX in the Regulation of Metabolic Activity.
AB  - Lysyl-phosphatidylglycerol is one of the components of the mycobacterial membrane
      that contributes to the resistance to cationic antimicrobial peptides, a host
      induced frontline defense against invading pathogens. Its production is catalyzed
      by LysX, a bifunctional protein with lysyl transferase and lysyl transfer RNA
      synthetase activity. Comparative proteome analysis of a lysX mutant of
      Mycobacterium avium strain 104 and the wild type indicated that the lysX mutant
      strain undergoes a transition in phenotype by switching the carbon metabolism to
      beta-oxidation of fatty acids, along with accumulation of lipid inclusions.
      Surprisingly, proteins associated with intracellular survival were upregulated in
      the lysX mutant, even during extracellular growth, preparing bacteria for the
      conditions occurring inside host cells. In line with this, the lysX mutant
      exhibited enhanced intracellular growth in human-blood-derived monocytes. Thus,
      our study exposes the significance of lysX in the metabolism and virulence of the
      environmental pathogen M. avium hominissuis.

PMID- 29471364
TI  - Association of early- and adult-life socioeconomic circumstances with muscle
      strength in older age.
AB  - Background: socioeconomic circumstances (SEC) during a person's lifespan
      influence a wide range of health outcomes. However, solid evidence of the
      association of early- and adult-life SEC with health trajectories in ageing is
      still lacking. This study assessed whether early-life SEC are associated with
      muscle strength in later life-a biomarker of health-and whether this relationship
      is caused by adult-life SEC and health behaviours. Methods: we used data from the
      Survey of Health Ageing and Retirement in Europe, a 12-year population-based
      cohort study with repeated measurement in six waves (2004-15) and retrospective
      collection of life-course data. Participants' grip strength was assessed by using
      a handheld dynamometer. Confounder-adjusted logistic mixed-effect models were
      used to examine the associations of early- and adult-life SEC with the risk of
      low muscle strength (LMS) in older age. Results: a total of 24,179 participants
      (96,375 observations) aged 50-96 living in 14 European countries were included in
      the analyses. Risk of LMS was increased with disadvantaged relative to advantaged
      early-life SEC. The association between risk of LMS and disadvantaged early-life
      SEC gradually decreased when adjusting for adult-life SEC for both sexes and with
      unhealthy behaviours for women. After adjusting for these factors, all
      associations between risk of LMS and early-life SEC remained significant for
      women. Conclusion: early-life SEC are associated with muscle strength after
      adjusting for adult-life SEC and behavioural lifestyle factors, especially in
      women, which suggests that early life may represent a sensitive period for future
      health.

PMID- 29471365
TI  - Integrator subunit 4 is a 'Symplekin-like' scaffold that associates with INTS9/11
      to form the Integrator cleavage module.
AB  - Integrator (INT) is a transcriptional regulatory complex associated with RNA
      polymerase II that is required for the 3'-end processing of both UsnRNAs and
      enhancer RNAs. Integrator subunits 9 (INTS9) and INTS11 constitute the catalytic
      core of INT and are paralogues of the cleavage and polyadenylation specificity
      factors CPSF100 and CPSF73. While CPSF73/100 are known to associate with a third
      protein called Symplekin, there is no paralog of Symplekin within INT raising the
      question of how INTS9/11 associate with the other INT subunits. Here, we have
      identified that INTS4 is a specific and conserved interaction partner of INTS9/11
      that does not interact with either subunit individually. Although INTS4 has no
      significant homology with Symplekin, it possesses N-terminal HEAT repeats similar
      to Symplekin but also contains a beta-sheet rich C-terminal region, both of which
      are important to bind INTS9/11. We assess three functions of INT including UsnRNA
      3'-end processing, maintenance of Cajal body structural integrity, and formation
      of histone locus bodies to conclude that INTS4/9/11 are the most critical of the
      INT subunits for UsnRNA biogenesis. Altogether, these results indicate that
      INTS4/9/11 compose a heterotrimeric complex that likely represents the Integrator
      'cleavage module' responsible for its endonucleolytic activity.

PMID- 29471366
TI  - Loss of Trust in the Neighborhood: The Experience of Older African Americans in
      Detroit.
AB  - Objective: Although evidence suggests that neighborhood conditions are related to
      stress and health, the processes connecting neighborhood conditions and stress
      for older minorities is little explored. The purpose of this analysis is to
      contribute new insights into this issue. Method: We conducted a qualitative
      analysis as part of a larger mixed methods study of 100 African Americans aged 55
      years and older living in neighborhoods of varying quality in Detroit, Michigan.
      A subsample of (n = 20) older adults took photographs of bothersome aspects of
      their neighborhoods and participated in in-depth photo-elicitation interviews.
      Data were analyzed using a grounded theory approach. Results: "Loss of trust in
      the neighborhood" emerged as the core category to explain how older African
      Americans in our sample experienced neighborhood stressors in their daily lives.
      Loss of trust in physical, social, and institutional dimensions of the
      neighborhood contributed to the core category. Discussion : The life course of
      neighborhoods and the trust placed in them appears to be intimately connected to
      the well-being of older African Americans. We therefore hypothesize that a
      fundamental pathway through which neighborhood stressors are experienced for
      older African Americans in United States "Rust Belt" cities is the multifaceted
      loss of trust in the neighborhood.

PMID- 29471368
TI  - Human Factors Risk Analyses of a Doffing Protocol for Ebola-Level Personal
      Protective Equipment: Mapping Errors to Contamination.
AB  - Background: Doffing protocols for personal protective equipment (PPE) are
      critical for keeping healthcare workers (HCWs) safe during care of patients with
      Ebola virus disease. We assessed the relationship between errors and self
      contamination during doffing. Methods: Eleven HCWs experienced with doffing Ebola
      level PPE participated in simulations in which HCWs donned PPE marked with
      surrogate viruses (phi6 and MS2), completed a clinical task, and were assessed
      for contamination after doffing. Simulations were video recorded, and a failure
      modes and effects analysis and fault tree analyses were performed to identify
      errors during doffing, quantify their risk (risk index), and predict
      contamination data. Results: Fifty-one types of errors were identified, many
      having the potential to spread contamination. Hand hygiene and removing the
      powered air purifying respirator (PAPR) hood had the highest total risk indexes
      (111 and 70, respectively) and number of types of errors (9 and 13,
      respectively). phi6 was detected on 10% of scrubs and the fault tree predicted a
      10.4% contamination rate, likely occurring when the PAPR hood inadvertently
      contacted scrubs during removal. MS2 was detected on 10% of hands, 20% of scrubs,
      and 70% of inner gloves and the predicted rates were 7.3%, 19.4%, 73.4%,
      respectively. Fault trees for MS2 and phi6 contamination suggested similar
      pathways. Conclusions: Ebola-level PPE can both protect and put HCWs at risk for
      self-contamination throughout the doffing process, even among experienced HCWs
      doffing with a trained observer. Human factors methodologies can identify error
      prone steps, delineate the relationship between errors and self-contamination,
      and suggest remediation strategies.

PMID- 29471367
TI  - Evolution of genes associated with gynoecium patterning and fruit development in
      Solanaceae.
AB  - Background and Aims: The genetic basis of fruit development has been extensively
      studied in Arabidopsis, where major transcription factors controlling valve
      identity (i.e. FRUITFULL), replum development (i.e. REPLUMLESS) and the
      differentiation of the dehiscence zones (i.e. SHATTERPROOF, INDEHISCENT and
      ALCATRAZ) have been identified. This gene regulatory network in other flowering
      plants is influenced by duplication events during angiosperm diversification.
      Here we aim to characterize candidate fruit development genes in the Solanaceae
      and compare them with those of Brassicaceae. Methods: ALC/SPT, HEC/IND, RPL and
      AG/SHP homologues were isolated from publicly available databases and from our
      own transcriptomes of Brunfelsia australis and Streptosolen jamesonii. Maximum
      likelihood phylogenetic analyses were performed for each of the gene lineages.
      Shifts in protein motifs, as well as expression patterns of all identified
      homologues, are shown in dissected floral organs and fruits in different
      developmental stages of four Solanaceae species exhibiting different fruit types.
      Key Results: Each gene lineage has undergone different duplication time-points,
      resulting in very different genetic complements in the Solanaceae when compared
      with the Brassicaceae. In general, Solanaceae species have more copies of HEC1/2
      and RPL than Brassicaceae, have fewer copies of SHP and the same number of copies
      of AG, ALC and SPT. Solanaceae lack IND orthologues, but have pre-duplication
      HEC3 homologues. The expression analyses showed opposite expression of SPT and
      ALC orthologues between dry- and fleshy-fruited species during fruit maturation.
      Fleshy-fruited species turn off RPL and SPT orthologues during maturation.
      Conclusions: The gynoecium patterning and fruit developmental genetic network in
      the Brassicaceae cannot be directly extrapolated to the Solanaceae. In Solanaceae
      ALC, SPT and RPL contribute differently to maturation of dry dehiscent and fleshy
      fruits, whereas HEC genes are not generally expressed in the gynoecium. RPL genes
      have broader expression patterns than expected.

PMID- 29471369
TI  - Genome-wide association study of Stayability and Heifer Pregnancy in Red Angus
      cattle.
AB  - Reproductive performance is the most important component of cattle production
      from the standpoint of economic sustainability of commercial beef enterprises.
      Heifer Pregnancy (HPG) and Stayability (STAY) genetic predictions are 2 selection
      tools published by the Red Angus Association of America (RAAA) to assist with
      improvements in reproductive performance. Given the importance of HPG and STAY to
      the profitability of commercial beef enterprises, the objective of this study was
      to identify QTL associated with both HPG and STAY in Red Angus cattle. A genome
      wide association study (GWAS) was performed using deregressed HPG and STAY EBV,
      calculated using a single-trait animal model and a 3-generation pedigree with
      data from the Spring 2015 RAAA National Cattle Evaluation. Each individual animal
      possessed 74,659 SNP genotypes. Individual animals with a deregressed EBV
      reliability > 0.05 were merged with the genotype file and marker quality control
      was performed. Criteria for sifting genotypes consisted of removing those markers
      where any of the following were found: average call rate less than 0.85, minor
      allele frequency < 0.01, lack of Hardy-Weinberg equilibrium (P < 0.0001), or
      extreme linkage disequilibrium (r2 > 0.99). These criteria resulted in 2,664
      animals with 62,807 SNP available for GWAS. Association studies were performed
      using a Bayes Cpi model in the BOLT software package. Marker significance was
      calculated as the posterior probability of inclusion (PPI), or the number of
      instances a specific marker was sampled divided by the total number of samples
      retained from the Markov chain Monte Carlo chains. Nine markers, with a PPI >= 3%
      were identified as QTL associated with HPG on BTA 1, 11, 13, 23, and 29. Twelve
      markers, with a PPI >= 75% were identified as QTL associated with STAY on BTA 6,
      8, 9, 12, 15, 18, 22, and 23.

PMID- 29471370
TI  - Competitive ability of Capsella species with different mating systems and ploidy
      levels.
AB  - Background and Aims: Capsella is a model genus for studying the transition from
      outcrossing to selfing, with or without change in ploidy levels. The genomic
      consequences and changes in reproductive traits (selfing syndrome) associated
      with these shifts have been studied in depth. However, potential ecological
      divergence among species of the genus has not been determined. Among ecological
      traits, competitive ability could be relevant for selfing evolution, as selfing
      has been shown to be statistically associated with reduced competitiveness in a
      recent meta-analysis. Methods: We assessed the effect of competition on three
      Capsella species differing in their mating system and ploidy level. We used an
      experimental design where fitness related traits were measured in focal
      individuals with and without competitors. Key Results: The diploid selfer (C.
      rubella) was most sensitive to competition, whereas the tetraploid selfer (C.
      bursa-pastoris) performed the best, with the diploid outcrosser (C. grandiflora)
      being intermediate. Conclusions: These results add to the detailed
      characterization of Capsella species and highlight the possible roles of
      ecological context and ploidy in the evolutionary trajectories of selfing
      species.

PMID- 29471371
TI  - Digital holography and its multidimensional imaging applications: a review.
AB  - In this review, we introduce digital holographic techniques and recent progress
      in multidimensional sensing by using digital holography. Digital holography is an
      interferometric imaging technique that does not require an imaging lens and can
      be used to perform simultaneous imaging of multidimensional information, such as
      three-dimensional structure, dynamics, quantitative phase, multiple wavelengths
      and polarization state of light. The technique can also obtain a holographic
      image of nonlinear light and a three-dimensional image of incoherent light with a
      single-shot exposure. The holographic recording ability of this technique has
      enabled a variety of applications.

PMID- 29471372
TI  - A Multistate Outbreak of Human Salmonella Agona Infections Associated With
      Consumption of Fresh, Whole Papayas Imported From Mexico-United States, 2011.
AB  - Background: Nontyphoidal Salmonella causes ~1 million food-borne infections
      annually in the United States. We began investigating a multistate outbreak of
      Salmonella serotype Agona infections in April 2011. Methods: A case was defined
      as infection with the outbreak strain of Salmonella Agona occurring between 1
      January and 25 August 2011. We developed hypotheses through iterative interviews.
      Product distribution analyses and traceback investigations were conducted. The
      Food and Drug Administration (FDA) tested papayas from Mexico for Salmonella.
      Results: We identified 106 case patients from 25 states. Their median age was 21
      years (range, 1-91). Thirty-nine of 61 case patients (64%) reported
      Hispanic/Latino ethnicity; 11 of 65 (17%) travelled to Mexico before illness.
      Thirty-two of 56 case patients (57%) reported papaya consumption. Distribution
      analyses revealed that three firms, including Distributor A, distributed papaya
      to geographic areas that aligned with both the location and timing of illnesses.
      Traceback of papayas purchased by ill persons in four states identified
      Distributor A as the common supplier. FDA testing isolated the outbreak strain
      from a papaya sample collected at distributor A and from another sample collected
      at the US-Mexico border, destined for distributor A. FDA isolated Salmonella
      species from 62 of 388 papaya import samples (16%). The investigation led to a
      recall of fresh, whole papayas from Distributor A and an FDA import alert for all
      papayas from Mexico. Conclusions: This is the first reported Salmonella outbreak
      in the United States linked to fresh, whole papayas. The outbreak highlights
      important issues regarding the safety of imported produce.

PMID- 29471373
TI  - Deep Brain Stimulation of the Subthalamic Nucleus Parameter Optimization for
      Vowel Acoustics and Speech Intelligibility in Parkinson's Disease.
AB  - Purpose: The settings of 3 electrical stimulation parameters were adjusted in 12
      speakers with Parkinson's disease (PD) with deep brain stimulation of the
      subthalamic nucleus (STN-DBS) to examine their effects on vowel acoustics and
      speech intelligibility. Method: Participants were tested under permutations of
      low, mid, and high STN-DBS frequency, voltage, and pulse width settings. At each
      session, participants recited a sentence. Acoustic characteristics of vowel
      production were extracted, and naive listeners provided estimates of speech
      intelligibility. Results: Overall, lower-frequency STN-DBS stimulation (60 Hz)
      was found to lead to improvements in intelligibility and acoustic vowel
      expansion. An interaction between speaker sex and STN-DBS stimulation was found
      for vowel measures. The combination of low frequency, mid to high voltage, and
      low to mid pulse width led to optimal speech outcomes; however, these settings
      did not demonstrate significant speech outcome differences compared with the
      standard clinical STN-DBS settings, likely due to substantial individual
      variability. Conclusions: Although lower-frequency STN-DBS stimulation was found
      to yield consistent improvements in speech outcomes, it was not found to
      necessarily lead to the best speech outcomes for all participants. Nevertheless,
      frequency may serve as a starting point to explore settings that will optimize an
      individual's speech outcomes following STN-DBS surgery. Supplemental Material:
      https://doi.org/10.23641/asha.5899228.

PMID- 29471374
TI  - Opponent's comments.

PMID- 29471375
TI  - Increasing stomatal conductance in response to rising atmospheric CO2.

PMID- 29471376
TI  - Corrigendum.

PMID- 29471377
TI  - TNF inhibitor treatment is associated with a lower risk of hand osteoarthritis
      progression in rheumatoid arthritis patients after 10 years.
AB  - Objective: To investigate the effect of TNF inhibitors (TNFis) on incidental and
      progressive hand OA in recent-onset RA patients after a 10 year follow-up.
      Methods: Radiographs of 262 RA patients (mean age 52 years, 66% women) from the
      BeSt study were scored for osteophytes in DIP/PIP joints using the Osteoarthritis
      Research Society International atlas (0-3; summed score 0-54) and according to
      the Kellgren-Lawrence (KL) score (0-4; summed score 0-72) at baseline and 10 year
      follow-up. TNFi treatment was assessed on visits every 3 months. Associations
      between TNFi treatment and hand OA were analysed on the patient and joint level
      using generalized linear models and generalized estimating equations,
      respectively. Results: Fifty-eight percent of the patients were treated with
      TNFi, with a median duration of 42 months. A total of 143 patients (55%) had hand
      OA in any IP joint at baseline based on the Osteoarthritis Research Society
      International osteophyte score. On the patient level, TNFi treatment duration did
      not affect incidental hand OA. However, every month of TNFi treatment resulted in
      a reduced relative risk (RR) of hand OA progression in DIP joints [relative risk
      (RR) 0.987 (95% CI 0.978, 0.996)] but not in PIP joints. On the joint level, the
      effect on hand OA progression was observed in DIP joints [RR 0.996 (95% CI 0.991,
      1.000)] but not in PIP joints. The results from the KL score analyses were
      comparable to the osteophyte score. Conclusion: TNFi treatment was associated
      with a reduced risk on radiographic hand OA progression in DIP joints but not in
      PIP joints after 10 years. Although the effect sizes are small, these results
      provide evidence for influence of TNF-alpha in hand OA pathogenesis.

PMID- 29471378
TI  - Communicative Function Use of Preschoolers and Mothers From Differing Racial and
      Socioeconomic Groups.
AB  - Purpose: This study explores whether communicative function (CF: reasons for
      communicating) use differs by socioeconomic status (SES), race/ethnicity, or
      gender among preschoolers and their mothers. Method: Mother-preschooler dyads (N
      = 95) from the National Center for Early Development and Learning's (2005) study
      of family and social environments were observed during 1 structured learning and
      free-play interaction. CFs were coded by trained independent raters. Results:
      Children used all CFs at similar rates, but those from low SES homes produced
      fewer utterances and less reasoning, whereas boys used less self-maintaining and
      more predicting. African American mothers produced more directing and less
      responding than European American and Latino American mothers, and Latino
      American mothers produced more utterances than European American mothers. Mothers
      from low SES homes did more directing and less responding. Conclusions: Mothers
      exhibited more sociocultural differences in CFs than children; this suggests that
      maternal demographic characteristics may influence CF production more than child
      demographics at school entry. Children from low SES homes talking less and boys
      producing less self-maintaining coincided with patterns previously detected in
      pragmatic literature. Overall, preschoolers from racial/ethnic minority and low
      SES homes were not less deft with CF usage, which may inform how their pragmatic
      skills are described. Supplemental Material:
      https://doi.org/10.23641/asha.5890255.

PMID- 29471379
TI  - Do Women and Men Have the Same Patterns of Multiple Occupational Carcinogenic
      Exposures? Results from a Cohort of Cancer Patients.
AB  - Complex exposure situations are frequent at the workplace, but few studies have
      characterized multiple occupational carcinogenic exposures (MOCE) and their
      gendered differences across jobs' characteristics. We assessed MOCE separately in
      male and female jobs and identified patterns of MOCE at job level. Participants
      (834 men and 183 women) were cancer patients recruited between March 2002 and
      December 2010 in the ongoing SCOP93 cohort study, Seine-Saint-Denis department,
      France. Job histories were collected through personal interviews, and
      carcinogenic exposures were assessed by a multidisciplinary expert committee
      using a list of 53 carcinogens. Proportion of MOCE (i.e. >=2 carcinogens) was
      assessed for male and female jobs separately. Principal component analysis
      combined with hierarchical ascendant classification was used to identify patterns
      of MOCE. Among the 5202 male jobs and 885 female jobs, respectively 42 and 9%
      were multi-exposed. Blue-collar workers and jobs in the construction and industry
      sectors had the highest rates of MOCE, contrasting with jobs held in recent
      periods (>=1997) and by patients aged >=45 years at job start. A gradient of MOCE
      was also observed according to occupational segregation for both men and women.
      Eight patterns of MOCE were identified among male jobs: widespread carcinogens,
      mixed silica dust, heavy metals/combustion products, organic compounds/radiation,
      metal working, solvents/heavy metals, wood dust/formaldehyde/pesticides, and fuel
      exhausts. Three patterns of MOCE were found among female jobs: biological/organic
      compounds, industrial working, and fuel exhausts. Some patterns of MOCE were job
      specific, whereas other patterns were found across different occupations. These
      results suggest that patterns of MOCE partly differ between men and women. They
      stress the importance of gendering multiple exposure assessment studies and point
      out the inadequacy of occupational disease compensation systems based on a single
      factor and non-gendered approach of carcinogenesis, ignoring differences between
      men and women in complex occupational exposure situations.

PMID- 29471380
TI  - Dysarthria in Mandarin-Speaking Children With Cerebral Palsy: Speech Subsystem
      Profiles.
AB  - Purpose: This study explored the speech characteristics of Mandarin-speaking
      children with cerebral palsy (CP) and typically developing (TD) children to
      determine (a) how children in the 2 groups may differ in their speech patterns
      and (b) the variables correlated with speech intelligibility for words and
      sentences. Method: Data from 6 children with CP and a clinical diagnosis of
      moderate dysarthria were compared with data from 9 TD children using a multiple
      speech subsystems approach. Acoustic and perceptual variables reflecting 3 speech
      subsystems (articulatory-phonetic, phonatory, and prosodic), and speech
      intelligibility, were measured based on speech samples obtained from the Test of
      Children's Speech Intelligibility in Mandarin (developed in the lab for the
      purpose of this research). Results: The CP and TD children differed in several
      aspects of speech subsystem function. Speech intelligibility scores in children
      with CP were influenced by all 3 speech subsystems, but articulatory-phonetic
      variables had the highest correlation with word intelligibility. All 3 subsystems
      influenced sentence intelligibility. Conclusion: Children with CP demonstrated
      deficits in speech intelligibility and articulation compared with TD children.
      Better speech sound articulation influenced higher word intelligibility, but did
      not benefit sentence intelligibility.

PMID- 29471382
TI  - Gendered Safety and Health Risks in the Construction Trades.
AB  - Objectives: Despite women's increased representation in the overall workforce,
      construction remains a male-dominated industry. Prior studies have noted that the
      hazardous workplace environment combined with a culture that can be
      discriminatory and openly hostile can threaten women workers' health and safety.
      However, little information exists about the current physical and psychosocial
      hazards at work affecting tradeswomen. Methods: We examined differences in
      workplace exposure between women and men, and the association of these exposures
      with self-reported stress and work injury, in order to highlight how gendered
      conditions of work negatively affect tradeswomen's health. A holistic view of
      health that included the influence of both home and work spheres as well as
      hazards related to women's social experience was considered. Almost 300 workers
      (198 tradeswomen and 93 tradesmen) throughout Washington State completed surveys.
      We used descriptive statistics to compare exposures between genders, and logistic
      regression to model the association between psychosocial exposures and injury and
      stress outcomes. Results: We found that women were significantly more likely than
      men to report high perceived stress (31 and 18%, respectively) and being injured
      at work in the past year (31 and 12%, respectively). Ten of the 12 work-related
      psychosocial exposures were found to be associated with either stress (job
      strain, gender and age discrimination, bullying, work/life balance, isolation,
      sexual harassment, safety climate, and social support) or injury (gender
      discrimination, bullying, overcompensation, and sexual harassment) for women.
      Conclusions: The industry continues to lag in supporting tradeswomen's health and
      safety needs. This study suggests that multiple exposures (including
      discrimination, overcompensation, and work/life balance) have an important impact
      on worker well-being. The findings underscore the complex interaction of gender,
      psychosocial exposures, and occupational risks, and indicate areas for
      intervention.

PMID- 29471381
TI  - Efficacy of Vedolizumab in Fistulising Crohn's Disease: Exploratory Analyses of
      Data from GEMINI 2.
AB  - Background and Aims: Medical management of fistulising Crohn's disease [CD] is
      constrained by the limited number of available therapies. We evaluated the
      efficacy of vedolizumab, a gut-selective alpha4beta7 integrin antagonist approved
      for treating moderately to severely active CD, in a subpopulation of patients
      with fistulising CD who participated in the GEMINI 2 trial [NCT00783692].
      Methods: Exploratory analyses of data from the GEMINI 2 trial were conducted in
      461 responders to 6-week vedolizumab induction therapy who received maintenance
      placebo [VDZ/PBO, N = 153] or vedolizumab [VDZ/VDZ, N = 308]. Fistula closure
      rates were assessed at Weeks 14 and 52, and the time to fistula closure was
      analysed by the Cox proportional hazards model with adjustments for significant
      covariates. Results: At entry into the maintenance period, 153 [33%] patients had
      a history of fistulising disease and 57 [12%] patients had >=1 active draining
      fistula. By Week 14, 28% of VDZ/VDZ-treated patients compared with 11% of VDZ/PBO
      treated patients (95% confidence interval [CI], -11.4 to 43.9) achieved fistula
      closure. Corresponding rates at Week 52 were 31% and 11% (absolute risk reduction
      [ARR]: 19.7%; 95% CI, -8.9 to 46.2). Similarly, VDZ/VDZ-treated patients had
      faster time to fistula closure and were more likely to have fistula closure at
      Week 52 [33% vs 11%; HR: 2.54; 95% CI, 0.54-11.96]. Prior failure of antibiotic
      therapy was a negative predictor of fistula closure [HR: 0.217; 95% CI, 0.059
      0.795; p = 0.021], whereas trough vedolizumab concentrations did not affect
      closure rates. Conclusions: Our findings are consistent with the beneficial
      effect of vedolizumab treatment for fistulising CD.

PMID- 29471384
TI  - Increased BMI in children-an indicator for less compliance during orthodontic
      treatment with removable appliances.
AB  - Aim: To assess whether or not childhood overweight is associated with lower
      levels of compliance during orthodontic therapy with removable appliances.
      Materials and methods: Starting in 2011, all upper expansion plates and Sander II
      appliances were equipped with a Theramon(r) microsensor chip to assess appliance
      wear time objectively. According to their pre-treatment, BMI normal weight
      patients were matched to consecutively treated overweight or obese patients by
      gender, age, and appliance type. Cooperation was assessed with microelectronic
      wear time documentation over a period of at least 6 months. Results: A total of
      50 patients (25 overweight, 25 normal weight) with upper expansion plates and 64
      patients (32 overweight, 32 normal weight) with Sander II appliances were
      analysed. Spearman Rho coefficients showed an indirect association between BMI
      and appliance wear time, indicating that the higher the BMI, the less the
      patients wore their appliances (P < 0.05). Furthermore, both normal- and
      overweight children wore upper expansion plates significantly more than Sander II
      appliances (P < 0.05). Although no gender-specific difference was found (P =
      0.723), an age-related correlation could be verified, indicating a decrease in
      wear time with increasing age (P < 0.05). Conclusions: An increased BMI appears
      to be a risk factor for less appliance wear during orthodontic treatment with
      removable appliances. Additional factors which influenced cooperation during
      treatment with removable appliances were patient age and appliance type.

PMID- 29471383
TI  - Genetic analysis of calf health in Charolais beef cattle.
AB  - The objective of this study was to investigate the factors that influence calf
      health and survival in Charolais cattle. Data from 2,740 calves, originating from
      16 French farms and observed from birth until 30 d of age, were analyzed using
      models that took account of direct genetic, maternal genetic, and common
      environmental effects. Both direct and maternal genetic parameters were estimated
      for birth weight (BW), calving ease (CE), neonatal vitality (NV), survival at 30
      d (Surv), and umbilical infection and diarrhea at different ages (0 to 5 d: Umb1
      and Diar1; 6 to 20 d: Umb2 and Diar2; and 21 to 30 d: Umb3 and Diar3). The
      heritability values for direct and maternal genetic effects were, 0.026 (SE =
      0.027) and 0.096 (SE = 0.042) for Surv, 0.280 (SE = 0.063) and 0.063 (SE = 0.038)
      for BW, 0.129 (SE = 0.041) and 0 for CE, 0.073 (SE = 0.035) and 0 for NV, 0.071
      (SE = 0.038) and 0.017 (SE = 0.026) for Umb1, 0 and 0.082 (SE = 0.029) for Umb2,
      0 and 0.044 (SE = 0.030) for Diar1, 0.016 (SE = 0.022) and 0.012 (SE = 0.026) for
      Diar2, and 0.016 (SE = 0.028) and 0 for Diar3, respectively. Significant genetic
      variability in beef cattle was thus revealed for five calf health traits: NV,
      Surv, Diar1, Umb1, and Umb2. In addition, for three traits (Surv, Diar1, and
      Umb2), maternal genetic effects clearly contributed more to health performance
      than direct genetic effects. Estimates of genetic correlation between traits
      varied markedly (from 0 to 1 in absolute values) depending on the traits in
      question, the age for a given trait, and the type (direct or maternal) of the
      genetic effects considered. These results suggest that not all health traits in
      Charolais cattle can be improved simultaneously, and breeders will therefore have
      to prioritize certain traits of interest in their breeding objectives. Overall,
      our results demonstrate the potential utility of collecting and integrating data
      on calf diseases, NV and survival in future beef cattle breeding programs. To
      ensure appropriate biological and genetic evaluations of calf health performance,
      it is important to accurately describe the phenotypes for diarrhea and umbilical
      infections (in terms of age ranges) and account for maternal genetic and common
      environmental effects that explain calf health performance traits. Further
      investigation and improved data collection are now necessary to maximize the
      efficiency of breeding schemes designed to simultaneously improve production and
      health traits.

PMID- 29471385
TI  - Functional neural correlates of slower gait among older adults with mild
      cognitive impairment.
AB  - Background: Subtle, but observable, changes in mobility often exist among older
      adults with mild cognitive impairment (MCI). Notably, these changes are not
      inconsequential. Therefore, there is a strong interest to better understand the
      underlying neural correlates of gait slowing among older adults with MCI. In this
      study, we aimed to characterize patterns of functional connectivity associated
      with slower gait speed in older adults with MCI. Methods: 49 participants >= 60
      years with MCI were included in the cross-sectional study. All participants
      underwent assessments of gait speed and resting state functional magnetic
      resonance imaging. Results: In this sample of older adults with MCI, slower usual
      gait was characterized by altered connectivity between the sensorimotor network
      (SMN) and the frontoparietal network (FPN) (p<0.05) - specifically, slower usual
      gait was associated with greater connectivity between the supplementary motor
      area (SMA) and the bilateral ventral visual (BVV) cortices (p=0.01); lower
      connectivity between the SMA and the bilateral superior lateral occipital cortex
      (BSLOC) (p<0.01); and lower connectivity between the SMA and the bilateral
      frontal eye field (BFEF) (p<0.01). Conclusion: Altered inter-network functional
      connectivity between the SMN and FPN may be a neural mechanism for slowing of
      gait in older adults with MCI.

PMID- 29471386
TI  - First Report of CTX-M-15 Salmonella Typhi From England.

PMID- 29471388
TI  - Novel Behavioral and Neural Evidences for Age-Related changes in Force
      complexity.
AB  - This study investigated age-related changes in behavioral and neural complexity
      for a polyrhythmic movement, which appeared to be an exception to the loss of
      complexity hypothesis. Young (n = 15; age = 24.2 years) and older (15; 68.1
      years) adults performed low-level force-tracking with isometric index abduction
      to couple a compound sinusoidal target. Multiscale entropy (MSE) of tracking
      force and inter-spike interval (ISI) of motor unit (MU) in the first dorsal
      interosseus muscle were assessed. The MSE area of tracking force at shorter time
      scales of older adults was greater (more complex) than that of young adults,
      whereas an opposite trend (less complex for the elders) was noted at longer time
      scales. The MSE area of force fluctuations (the stochastic component of the
      tracking force) were generally smaller (less complex) for older adults. Along
      with greater mean and coefficient of ISI, the MSE area of the cumulative
      discharge rate of elders tended to be lower (less complex) than that of young
      adults. In conclusion, age-related complexity changes in polyrhythmic force
      tracking depended on the time scale. The adaptive behavioral consequences could
      be multifactorial origins of the age-related impairment in rate coding, increased
      discharge noises, and lower discharge complexity of pooled MUs.

PMID- 29471387
TI  - Heavy Cannabis Use Associated With Reduction in Activated and Inflammatory Immune
      Cell Frequencies in Antiretroviral Therapy-Treated Human Immunodeficiency Virus
      Infected Individuals.
AB  - Background: Cannabis is a widely used drug in the United States, and the
      frequency of cannabis use in the human immunodeficiency virus (HIV)-infected
      population is disproportionately high. Previous human and macaque studies suggest
      that cannabis may have an impact on plasma viral load; however, the relationship
      between cannabis use and HIV-associated systemic inflammation and immune
      activation has not been well defined. Methods: The impact of cannabis use on
      peripheral immune cell frequency, activation, and function was assessed in 198
      HIV-infected, antiretroviral-treated individuals by flow cytometry. Individuals
      were categorized into heavy, medium, or occasional cannabis users or noncannabis
      users based on the amount of the cannabis metabolite 11-nor-carboxy
      tetrahydrocannabinol (THC-COOH) detected in plasma by mass spectrometry. Results:
      Heavy cannabis users had decreased frequencies of human leukocyte antigen (HLA)
      DR+CD38+CD4+ and CD8+ T-cell frequencies, compared to frequencies of these cells
      in non-cannabis-using individuals. Heavy cannabis users had decreased frequencies
      of intermediate and nonclassical monocyte subsets, as well as decreased
      frequencies of interleukin 23- and tumor necrosis factor-alpha-producing antigen
      presenting cells. Conclusions: While the clinical implications are unclear, our
      findings suggest that cannabis use is associated with a potentially beneficial
      reduction in systemic inflammation and immune activation in the context of
      antiretroviral-treated HIV infection.

PMID- 29471389
TI  - The effect of paternal factors on perinatal and paediatric outcomes: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Maternal factors, including increasing childbearing age and various
      life-style factors, are associated with poorer short- and long-term outcomes for
      children, whereas knowledge of paternal parameters is limited. Recently,
      increasing paternal age has been associated with adverse obstetric outcomes,
      birth defects, autism spectrum disorders and schizophrenia in children. OBJECTIVE
      AND RATIONALE: The aim of this systematic review is to describe the influence of
      paternal factors on adverse short- and long-term child outcomes. SEARCH METHODS:
      PubMed, Embase and Cochrane databases up to January 2017 were searched. Paternal
      factors examined included paternal age and life-style factors such as body mass
      index (BMI), adiposity and cigarette smoking. The outcome variables assessed were
      short-term outcomes such as preterm birth, low birth weight, small for
      gestational age (SGA), stillbirth, birth defects and chromosomal anomalies. Long
      term outcome variables included mortality, cancers, psychiatric
      diseases/disorders and metabolic diseases. The systematic review follows PRISMA
      guidelines. Relevant meta-analyses were performed. OUTCOMES: The search included
      14 371 articles out of which 238 met the inclusion criteria, and 81 were included
      in quantitative synthesis (meta-analyses). Paternal age and paternal life-style
      factors have an association with adverse outcome in offspring. This is
      particularly evident for psychiatric disorders such as autism, autism spectrum
      disorders and schizophrenia, but an association is also found with stillbirth,
      any birth defects, orofacial clefts and trisomy 21. Paternal height, but not BMI,
      is associated with birth weight in offspring while paternal BMI is associated
      with BMI, weight and/or body fat in childhood. Paternal smoking is found to be
      associated with an increase in SGA, birth defects such as congenital heart
      defects, and orofacial clefts, cancers, brain tumours and acute lymphoblastic
      leukaemia. These associations are significant although moderate in size, with
      most pooled estimates between 1.05 and 1.5, and none exceeding 2.0. WIDER
      IMPLICATIONS: Although the increased risks of adverse outcome in offspring
      associated with paternal factors and identified in this report represent serious
      health effects, the magnitude of these effects seems modest.

PMID- 29471390
TI  - Hybrid treatment for a type 2 Kommerell's aneurysm in a nonagenarian.

PMID- 29471392
TI  - Effects of fermentation on the hemolytic activity and degradation of Camellia
      oleifera saponins by Lactobacillus crustorum and Bacillus subtilis.
AB  - The saponins, as components of tea seed meal, are undesirable hemolytic
      components and should be degraded for reducing their hemolytic activity in order
      to be used in animal feed. In this study, beta-glucuronidase was verified to be a
      potent hydrolase of tea seed saponins to reduce their hemolytic activity and a
      beta-glucuronidase-producing Lactobacillus crustorum strain was screened from raw
      bovine milk. Next, solid-state fermentation with the isolated L. crustorum and a
      Bacillus subtilis natto strain, which can produce cellulase and hence improve the
      fermentation performance of tea seed meal, was carried out for detoxification of
      tea seed meal. The 50% hemolytic dosage (HD50) value of tea seed saponins was
      increased from 6.69 to 27.43 MUg mL-1. The results of LC-MS analysis showed that
      the percentage of saponin aglycones increased from 30.95 to 84.25% after the
      fermentation. According to the roles of sugar moieties in hemolytic activity, and
      the enzymatic hydrolysis characteristics of beta-glucuronidase, the degradation
      of tea seed saponins from glucosides to aglycones may contribute to the reduction
      of hemolytic activity. Therefore, tea seed meal may be used as animal feed after
      fermentation with the tested saponin-degrading microbial strains.

PMID- 29471391
TI  - Comparative efficacy of enrofloxacin to that of tulathromycin for the control of
      bovine respiratory disease and prevalence of antimicrobial resistance in
      Mannheimia haemolytica in calves at high risk of developing bovine respiratory
      disease.
AB  - Bovine respiratory disease (BRD) is the most common cause of morbidity and
      mortality in North American beef cattle. Mannheimia haemolytica is the bacterial
      pathogen most often isolated from cattle with BRD, and the prevalence of
      antimicrobial resistance (AMR) in this organism has increased in recent years.
      Antimicrobials are commonly used to prevent BRD in cattle at high risk of
      developing BRD; however, recent work would suggest that this practice might be
      one factor contributing to the increased prevalence of AMR in M. haemolytica. We
      hypothesized that the administration of the short-acting fluoroquinolone,
      enrofloxacin, would be just as effective as the long-acting triamilide,
      tulathromycin, in preventing BRD but would be less likely to select for AMR M.
      haemolytica in stocker calves at high risk of developing BRD. Three hundred forty
      one stocker calves were enrolled in the study with 172 calves in 4 pens being
      randomly assigned to treatment with enrofloxacin and 169 calves in 4 pens
      randomly assigned to treatment with tulathromycin. Calves within each treatment
      group were allocated to one of 4 replicate pens based on the week of enrollment.
      Of calves receiving enrofloxacin, 33.7% required treatment for BRD at least once
      within 45 d after arrival, compared with 18.3% of calves receiving tulathromycin
      (P = 0.040). The percentages of calves that required more than one treatment for
      BRD within 45 d after arrival did not differ statistically for those receiving
      enrofloxacin compared with those receiving tulathromycin (10.5% and 4.7%,
      respectively; P = 0.107) Likewise, the percentages of calves that died during the
      45-d follow-up period did not differ for those receiving enrofloxacin compared
      with those receiving tulathromycin (12.2% and 10.1%, respectively; P = 0.592).
      Mannheimia haemolytica was cultured from 11% of calves sampled at arrival and
      from 50% of calves sampled at revaccination 14 to 17 d later. There was a
      significanst effect of sampling time on the proportion of calves carrying
      multidrug-resistant (MDR) isolates, with calves having a higher prevalence of MDR
      isolates at revaccination than arrival (100% vs. 13%; P < 0.001). Future research
      evaluating the impact of MDR on response to antimicrobial therapy is necessary.

PMID- 29471393
TI  - The Severe Impairment Profile: A Conceptual Shift.
AB  - Objective: The current study sought to evaluate and replicate the severe
      impairment profile (SIP) of the Word Memory Test (WMT) in patients referred for
      dementia evaluations. Method: The sample consisted of 125 patients referred for a
      neuropsychological evaluation at a large Veterans Affairs Medical Center.
      Patients were assigned a Clinical Dementia Rating (CDR) by blind raters, and were
      classified according to their performance on performance validity testing.
      Subsequent chart reviews were conducted to help in more accurately determining
      the presence of severe memory impairment likely due to an underlying dementing
      process versus poor effort/task engagement. Results: In our sample, 51% of
      patients failed easy WMT subtests and 93% of these patients obtained the SIP. The
      rates of failure on these easy subtests generally coincided with both more
      severely impaired CDR ratings, as well as more impaired delayed memory composite
      scores. Upon chart review, it was determined that there were likely a significant
      portion of classification errors using the SIP, with a positive posttest
      probability of impairment based on having the SIP being 65% as opposed to 28% for
      a negative result. Conclusions: Our findings suggest that the SIP does not appear
      to function effectively in a mixed dementia sample where there is increased
      potential for secondary gain. Additional concern is expressed regarding the
      overall likelihood of obtaining the SIP and subsequent inferential decisions
      related to obtaining an SIP. Future research should examine more optimal cut
      scores or alternative methods for more accurately classifying patients in
      different clinical contexts and patterns of impairment.

PMID- 29471394
TI  - hsa-let-7b-5p facilitates Mycobacterium tuberculosis survival in THP-1 human
      macrophages by Fas downregulation.
AB  - Tuberculosis continues to be one of the deadliest infectious diseases worldwide.
      MicroRNAs (miRNAs) are small non-coding entities that play critical role as post
      transcriptional regulators and are transcriptionally deregulated upon
      mycobacterial infection. In this study, we found significant upregulation of hsa
      let-7b-5p in Mycobacterium tuberculosis (MTB) infected THP-1 human macrophages.
      Concomitantly, we detected the reduced level of Fas protein, one of the targets
      of hsa-let-7b-5p, in MTB-infected THP-1 macrophages. Using luciferase assay, a
      direct interaction between hsa-let-7b-5p and the Fas 3?-untranslated region (3?
      UTR) was established. Inhibition of hsa-let-7b-5p augmented the apoptosis of THP
      1 cells enabling enhanced clearance of MTB. Our findings suggest that hsa-let-7b
      5p helps intracellular survival of MTB in THP-1 cells by downregulating Fas
      protein level. This highlights hsa-let-7b-5p as a potential therapeutic target
      for tuberculosis treatment.

PMID- 29471395
TI  - Origin and composition of cell-free DNA in spent medium from human embryo culture
      during preimplantation development.
AB  - STUDY QUESTION: What is the origin and composition of cell-free DNA in human
      embryo spent culture media? SUMMARY ANSWER: Cell-free DNA from human embryo spent
      culture media represents a mix of maternal and embryonic DNA, and the mixture can
      be more complex for mosaic embryos. WHAT IS KNOWN ALREADY: In 2016, ~300 000
      human embryos were chromosomally and/or genetically analyzed using
      preimplantation genetic testing for aneuploidies (PGT-A) or monogenic disorders
      (PGT-M) before transfer into the uterus. While progress in genetic techniques has
      enabled analysis of the full karyotype in a single cell with high sensitivity and
      specificity, these approaches still require an embryo biopsy. Thus, non-invasive
      techniques are sought as an alternative. STUDY DESIGN, SIZE, DURATION: This study
      was based on a total of 113 human embryos undergoing trophectoderm biopsy as part
      of PGT-A analysis. For each embryo, the spent culture media used between Day 3
      and Day 5 of development were collected for cell-free DNA analysis. In addition
      to the 113 spent culture media samples, 28 media drops without embryo contact
      were cultured in parallel under the same conditions to use as controls. In total,
      141 media samples were collected and divided into two groups: one for direct DNA
      quantification (53 spent culture media and 17 controls), the other for whole
      genome amplification (60 spent culture media and 11 controls) and subsequent
      quantification. Some samples with amplified DNA (N = 56) were used for aneuploidy
      testing by next-generation sequencing; of those, 35 samples underwent single
      nucleotide polymorphism (SNP) sequencing to detect maternal contamination.
      Finally, from the 35 spent culture media analyzed by SNP sequencing, 12 whole
      blastocysts were analyzed by fluorescence in situ hybridization (FISH) to
      determine the level of mosaicism in each embryo, as a possible origin for
      discordance between sample types. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Trophectoderm biopsies and culture media samples (20 MUl) underwent whole-genome
      amplification, then libraries were generated and sequenced for an aneuploidy
      study. For SNP sequencing, triads including trophectoderm DNA, cell-free DNA, and
      follicular fluid DNA were analyzed. In total, 124 SNPs were included with 90 SNPs
      distributed among all autosomes and 34 SNPs located on chromosome Y. Finally, 12
      whole blastocysts were fixed and individual cells were analyzed by FISH using
      telomeric/centromeric probes for the affected chromosomes. MAIN RESULTS AND THE
      ROLE OF CHANCE: We found a higher quantity of cell-free DNA in spent culture
      media co-cultured with embryos versus control media samples (P <= 0.001). The
      presence of cell-free DNA in the spent culture media enabled a chromosomal
      diagnosis, although results differed from those of trophectoderm biopsy analysis
      in most cases (67%). Discordant results were mainly attributable to a high
      percentage of maternal DNA in the spent culture media, with a median percentage
      of embryonic DNA estimated at 8%. Finally, from the discordant cases, 91.7% of
      whole blastocysts analyzed by FISH were mosaic and 75% of the analyzed
      chromosomes were concordant with the trophectoderm DNA diagnosis instead of the
      cell-free DNA result. LIMITATIONS, REASONS FOR CAUTION: This study was limited by
      the sample size and the number of cells analyzed by FISH. WIDER IMPLICATIONS OF
      THE FINDINGS: This is the first study to combine chromosomal analysis of cell
      free DNA, SNP sequencing to identify maternal contamination, and whole-blastocyst
      analysis for detecting mosaicism. Our results provide a better understanding of
      the origin of cell-free DNA in spent culture media, offering an important step
      toward developing future non-invasive karyotyping that must rely on the specific
      identification of DNA released from human embryos. STUDY FUNDING/ COMPETING
      INTEREST: This work was funded by Igenomix S.L. There are no competing interests.

PMID- 29471396
TI  - Involvement of Epigenetic Modifications of GABAergic Interneurons in Basolateral
      Amygdala in Anxiety-like Phenotype of Prenatally Stressed Mice.
AB  - Background: Prenatal stress is considered a risk factor for anxiety disorder.
      Downregulation in the expression of GABAergic gene, that is, glutamic acid
      decarboxylase 67, associated with DNA methyltransferase overexpression in
      GABAergic neurons has been regarded as a characteristic component of anxiety
      disorder. Prenatal stress has an adverse effect on the development of the
      basolateral amygdala, which is a key region in anxiety regulation. The aim of
      this study is to analyze the possibility of epigenetic alterations of GABAergic
      neurons in the basolateral amygdala participating in prenatal stress-induced
      anxiety. Methods: Behavioral tests were used to explore the prenatal stress
      induced anxiety behaviors of female adult mice. Real-time RT-PCR, western blot,
      chromatin immunoprecipitation, and electrophysiological analysis were employed to
      detect epigenetic changes of GABAergic system in the basolateral amygdala.
      Results: Prenatal stress mice developed an anxiety-like phenotype accompanied by
      a significant increase of DNA methyltransferase 1 and a reduced expression of
      glutamic acid decarboxylase 67 in the basolateral amygdala. Prenatal stress mice
      also showed the increased binding of DNA methyltransferase 1 and methyl CpG
      binding protein 2 to glutamic acid decarboxylase 67 promoter region. The decrease
      of glutamic acid decarboxylase 67 transcript was paralleled by an enrichment of 5
      methylcytosine in glutamic acid decarboxylase 67 promoter regions.
      Electrophysiological study revealed the increase of postsynaptic neuronal
      excitability in the cortical-basolateral amygdala synaptic transmission of
      prenatal stress mice. 5-Aza-deoxycytidine treatment restored the increased
      synaptic transmission and anxiety-like behaviors in prenatal stress mice via
      improving GABAergic system. Conclusion: The above results suggest that DNA
      epigenetic modifications of GABAergic interneurons in the basolateral amygdala
      participate in the etiology of anxiety-like phenotype in prenatal stress mice.

PMID- 29471397
TI  - A Conceptual Framework: The Musical Self as a Unique Pathway to Outcomes in the
      Acute Pediatric Health Setting.
AB  - This article reports on a project at the Royal Children's Hospital Melbourne in
      which the music therapy team synthesized their practice and related theories to
      propose a new conceptual framework for music therapy in their acute pediatric
      setting. The impetus for the project was the realization that in the process of
      producing key statements about the non-musical benefits of music therapy, the
      cost was often the suppression of information about the patient's unique musical
      potential as the major (mediating) pathway from referral reason, to music
      therapy, and to effective outcomes. The purpose of the project was to articulate
      how this team of clinicians conceive of the patient's musical self as the major
      theoretical pathway for music therapy in an evidence-based acute medical setting.
      The clinicians' shared reflexive process across six months involved robust
      directed discussion, annotation of shared reading, and documentation of all
      engagement in words and diagrams. The outcome was a consensus framework including
      three constructs: the place of music in the life of the infant, child, and young
      people, Culture and Context, and Musical Manifestations. The constructs were
      tested in a clinical audit, and found to be robustly inclusive. In addition to
      the conceptual framework, this project serves to demonstrate a process by which
      clinical teams may reflect on their individual practice and theory together to
      create a consensus stance for the overall service they provide in the one
      setting.

PMID- 29471398
TI  - Reducing BW loss during lactation in sows: a meta-analysis on the use of a
      nonstarch polysaccharide-hydrolyzing enzyme supplement.
AB  - A meta-analysis was performed on eight trials, which included a total of 992
      parity 1 to 8 lactating sows, to evaluate the effects of feeding xylanase which
      is the main enzyme activity present in the enzymatic complex (Rovabio Excel,
      Adisseo, France) supplement throughout lactation on the following sow performance
      factors: BW loss, feed intake, backfat depth, and piglet growth. Even a short
      period of enzyme supplementation during lactation led to a reduction in BW loss
      of approximately 3 kg per sow (P = 0.003). This reduction represented 1-2% of the
      BW of sows. This effect could be explained by an increase in feed energy intake
      and enhanced feed digestibility. Sows fed enzyme-supplemented diets exhibited
      greater DM, OM, and GE digestibilities (3.4, 3.9, and 4.2% increases,
      respectively; P < 0.001) than sows fed control diets. During lactation, sows lost
      from 19 to 25 kg of BW (i.e., approximately 10% of their BW), with a difference
      between parity groups (P < 0.001). Body reserve mobilization was decreased in
      sows fed enzyme-supplemented diets (-2.9 kg, P = 0.003), with a more pronounced
      effect in primiparous than multiparous sows when BW loss is expressed relative to
      total BW (-2.27 vs. -0.59%, respectively; P = 0.058). Enzyme supplementation also
      increased litter weight gain up to weaning, with a greater effect in litters from
      multiparous sows than those from primiparous sows (5.4 vs. 0.6 kg, respectively;
      P = 0.009). These results could be explained in part by the relationship between
      their NE intake and either variations in BW or litter weight gain (R2 = 0.51 and
      0.49, respectively; P < 0.001). Finally, the meta-analysis suggests that there
      are differences in the partitioning of the NE intake between growth and milk
      production and in relation to the sow's parity or physiological status. Extra
      energy released by enzyme is used for one of these functions (i.e., body
      mobilization reduction or greater milk export for litter gain).

PMID- 29471399
TI  - From genome-wide association studies to Mendelian randomization: novel
      opportunities for understanding cardiovascular disease causality, pathogenesis,
      prevention, and treatment.
AB  - The Mendelian randomization approach is an epidemiological study design
      incorporating genetic information into traditional epidemiological studies to
      infer causality of biomarkers, risk factors, or lifestyle factors on disease
      risk. Mendelian randomization studies often draw on novel information generated
      in genome-wide association studies on causal associations between genetic
      variants and a risk factor or lifestyle factor. Such information can then be used
      in a largely unconfounded study design free of reverse causation to understand if
      and how risk factors and lifestyle factors cause cardiovascular disease. If
      causation is demonstrated, an opportunity for prevention of disease is
      identified; importantly however, before prevention or treatment can be
      implemented, randomized intervention trials altering risk factor levels or
      improving deleterious lifestyle factors needs to document reductions in
      cardiovascular disease in a safe and side-effect sparse manner. Documentation of
      causality can also inform on potential drug targets, more likely to be successful
      than prior approaches often relying on animal or cell studies mainly. The present
      review summarizes the history and background of Mendelian randomization, the
      study design, assumptions for using the design, and the most common caveats,
      followed by a discussion on advantages and disadvantages of different types of
      Mendelian randomization studies using one or more samples and different levels of
      information on study participants. The review also provides an overview of
      results on many of the risk factors and lifestyle factors for cardiovascular
      disease examined to date using the Mendelian randomization study design.

PMID- 29471400
TI  - Increased dietary protein or free amino acids supply for heat stress pigs: effect
      on performance and carcass traits.
AB  - Heat stress (HS) pigs reduce their voluntary feed intake (VFI) and ingestion of
      indispensable amino acids (AA). Increasing the dietary crude protein (CP) content
      may help to correct the reduced AA intake by HS pigs, but it may further increase
      their body heat load. Increasing the AA intake by adding free AA to the diet does
      not affect the heat load of HS pigs. Two 21-d experiments were conducted. In Exp.
      1, 30 pigs (31.1 +/- 1.2 kg initial body weight) were used to determine the
      performance depression because of HS. Treatments were: thermo neutral pigs fed a
      22% CP control diet (TN-C); HS pigs fed the control diet (HS-C); HS pigs fed a
      14% CP, AA supplemented diet (HS-AA). HS pigs had lower ADG and Lys utilization
      efficiency, and consumed 20 and 25% less Lys and Thr, respectively, than the TN-C
      pigs (P < 0.05). In Exp. 2 (comparative slaughter), 25 pigs (33.6 +/- 0.65 kg
      initial body weight) were used to evaluate the effect of extra dietary AA either
      as protein-bound or free AA on the performance and carcass traits of HS pigs.
      Treatments were: control wheat-SBM-free Lys, Thr and Met diet (CON); diet with
      30% more CP than CON (HSxP); diet added with free AA to contain at least 25% more
      of each AA than the recommended level (HSxAA). Ambient temperature (AT) ranged
      from 27.7 to 37.7 degrees C, and body temperature (39.9 to 41.2 degrees C)
      followed a similar daily pattern as the AT did. There was no dietary treatment
      effect on daily feed and NE intake (P > 0.10), but the Lys, Thr, and Met intake
      was higher in pigs fed the HSxP or HSxAA diets than in pigs fed the CON diet (P <
      0.05). The daily weight gain (ADG) was not affected (P > 0.10) but G:F tended to
      be higher and the Lys utilization efficiency (ADG, g/g Lys intake) tended to be
      lower in HSxP pigs than in CON pigs (P < 0.10). The HSxAA pigs had higher ADG (P
      < 0.05), and tended to have higher weight of hot carcass and leg muscle, and the
      weight gain of hot carcass and leg muscle than the CON pigs (P < 0.10). The
      weight and daily weight gain of loin muscle was higher in the HSxAA than in the
      HSxP pigs (P < 0.05). Kidney weight and serum urea in HSxP pigs were higher than
      in CON and HSxAA pigs, but spleen weight was higher in HSxAA pigs than in CON and
      HSxP pigs (P < 0.05). These results confirm that HS reduces the VFI, and show
      that increased levels of AA either as free or protein-bound do not additionally
      reduce the VFI of HS pigs. These also show that extra free AA supply rather than
      protein-bound AA better ameliorate the reduced growth performance of HS pigs.

PMID- 29471401
TI  - Influence of Tree Size and Application Rate on Expression of Thiamethoxam in
      Citrus and Its Efficacy Against Diaphorina citri (Hemiptera: Liviidae).
AB  - Neonicotinoids are a key group of insecticides used to manage Diaphorina citri
      Kuwayama (Hemiptera: Liviidae), in Florida citrus. Diaphorina citri is the vector
      of Candidatus Liberibacter asiaticus, the presumed causal agent of huanglongbing,
      a worldwide disease of citrus. A two-season field study was conducted to evaluate
      the effect of tree size and application rate on the expression of thiamethoxam in
      young citrus following application to the soil. D. citri adult and nymph
      abundance was also correlated with thiamethoxam titer in leaves. Tree size and
      application rate each significantly affected thiamethoxam titer in leaf tissue.
      The highest mean thiamethoxam titer observed (33.39 ppm) in small trees (mean
      canopy volume = 0.08 m3) occurred after application of the high rate (0.74 g
      Platinum 75SG per tree) tested. There was a negative correlation between both
      nymph and adult abundance with increasing thiamethoxam titer in leaves. A
      concentration of 64.63 ppm thiamethoxam was required to reach a 1% probability of
      encountering a flush shoot with at least one adult D. citri, while 19.05 ppm was
      required for the same probability of encountering nymphs. The LC90 for the field
      population was 7.62 ppm thiamethoxam when administered through ingestion.
      Exposure to dosages as low as 7.62 ppm would likely result in sublethal exposure
      of some proportion of the population, which could exacerbate resistance
      development. Based on our results, subsequent work should investigate the use of
      neonicotinoids by foliar rather than soil application to maintain the chemical
      class in future insecticide management programs in Florida citrus.

PMID- 29471402
TI  - A Review of Sclerodermus Latreille, 1809 (Hymenoptera: Bethylidae) Infestations
      and Report of the First Case in North America North of Mexico.
AB  - Sclerodermus Latreille, 1809 (Hymenoptera: Bethylidae), are parasitoids of wood
      boring beetle larvae that can co-infest furniture and homes attacked by such
      larvae. This can result in the human inhabitants receiving stings from adult
      female wasps as they wander in search of new hosts. Herein, I report the first
      infestation of Sclerodermus macrogaster (Ashmead, 1887) of a home in North
      America and provide a review of Sclerodermus biology and clinical signs relevant
      to their pestiferous nature.

PMID- 29471403
TI  - Influence of distiller's dried grains with solubles on ram lamb growth and
      reproductive traits.
AB  - The hypothesis of this experiment was that increasing the inclusion level of
      distiller's dried grains with solubles (DDGS) in the diets would decrease semen
      quality but have no negative effects on growth performance. Following the removal
      of DDGS from the diet, it was hypothesized that the ram lambs would recover and
      become reproductively sound, independent of treatment. To test this hypothesis,
      Suffolk and Hampshire ram lambs (n = 112) were allocated to 4 treatments (n = 4
      pens per treatment; 7 rams per pen) in a completely randomized design. Dietary
      treatments were 60% corn, 25% oats, and 15% commercial lamb pellet (CON), 15% of
      the ration as DDGS substituted for corn (% DM basis; 15DDGS), 30% of the ration
      as DDGS substituted for corn (% DM basis; 30DDGS), and 45% of the ration as DDGS
      substituted for corn (% DM basis; 45DDGS). Lambs were fed for 112 d on their
      respective treatment, after which they were placed on the CON ration until day
      168. Lambs were weighed on consecutive d at the beginning (days 0 and 1) and end
      (days 167 and 168) of the study. Scrotal circumference was measured on all lambs
      on days 84, 112, 140, and 168. Semen samples were collected on a subset of 64
      rams (4 rams per pen) to evaluate semen quality on days 84, 112, 140, and 168.
      Blood samples were collected on the same subset of rams every 14 d throughout the
      study. A quadratic effect on BW on day 112 and overall BW (P = 0.03 and P =
      0.005, respectively), ADG on day 112 and overall ADG (P = 0.02 and P = 0.02,
      respectively), DMI (P = 0.007) on day 112, and a cubic effect (P = 0.05) for
      overall G:F were observed. Overall and day 168 scrotal circumference had a
      quadratic (P = 0.05) response. A linear increase in spermatozoa concentration on
      day 168 was observed (P = 0.03) as DDGS concentration increased in the treatment
      diets, although rams in this stage of the study were no longer receiving DDGS.
      Overall, testosterone concentrations exhibited a linear decrease (P = 0.005) as
      DDGS increased in the diet. The linear increase (P = 0.04) on day 168 in
      morphologically normal sperm as DDGS increased in the diets indicated that all
      rams, regardless of treatment, would have passed a reproductive soundness exam.
      In the current study, no negative effects were observed in lamb feedlot or
      reproductive traits due to increasing DDGS in the diet, indicating that DDGS may
      be included at levels up to 45% of growing lamb diets.

PMID- 29471404
TI  - The War on the Placenta: The Differing Battles of High-Fat Diet and Obesity.

PMID- 29471406
TI  - Multiobjective multifactor dimensionality reduction to detect SNP-SNP
      interactions.
AB  - Motivation: Single-nucleotide polymorphism (SNP)-SNP interactions (SSIs) are
      popular markers for understanding disease susceptibility. Multifactor
      dimensionality reduction (MDR) can successfully detect considerable SSIs.
      Currently, MDR-based methods mainly adopt a single-objective function (a single
      measure based on contingency tables) to detect SSIs. However, generally, a single
      measure function might not yield favorable results due to potential model
      preferences and disease complexities. Approach: This study proposes a
      multiobjective MDR (MOMDR) method that is based on a contingency table of MDR as
      an objective function. MOMDR considers the incorporated measures, including
      correct classification and likelihood rates, to detect SSIs and adopts set theory
      to predict the most favorable SSIs with cross-validation consistency. MOMDR
      enables simultaneously using multiple measures to determine potential SSIs.
      Results: Three simulation studies were conducted to compare the detection success
      rates of MOMDR and single-objective MDR (SOMDR), revealing that MOMDR had higher
      detection success rates than SOMDR. Furthermore, the Wellcome Trust Case Control
      Consortium dataset was analyzed by MOMDR to detect SSIs associated with coronary
      artery disease. Availability and implementation: MOMDR is freely available at
      https://goo.gl/M8dpDg. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29471405
TI  - Socioeconomic and Human Behavioral Factors Associated With Aedes aegypti
      (Diptera: Culicidae) Immature Habitat in Tucson, AZ.
AB  - Aedes aegypti (L.; Diptera: Culicidae) has been established in the southwestern
      United States for several decades, but relationships between humans and
      mosquitoes in this arid region are not well-characterized. In August 2012, the
      outdoor premises of 355 houses within 20 neighborhoods in Tucson, Arizona were
      surveyed for containers that could provide larval habitat for Ae. aegypti
      mosquitoes. At the same time, a knowledge, attitudes and practices (KAP)
      questionnaire was administered to a resident of each house surveyed for immature
      mosquitoes. The KAP questionnaire assessed respondents' knowledge and concerns
      about vector-borne illnesses as well as practices they used to avoid mosquitoes.
      Of the houses surveyed, 91% had at least one container present, and 64% had at
      least one container with standing water. On average, each house had 2.2
      containers with water at the time of the survey. The overall House Index
      (proportion of premises surveyed with at least one container with Ae. aegypti
      immatures present) was 13%. Based on questionnaire responses, there was a
      significant positive association between the number of residents in the home and
      the odds of finding Ae. aegypti positive containers on the premises, while
      household income showed a significant negative association. The reported
      frequency of checking for standing water was also significantly associated with
      the odds of finding immatures, although the nature of this association was
      ambiguous. Flower pots were the principal type of container with Ae. aegypti
      larvae. These findings show that larval habitat is widely available even in an
      arid environment and city with good housing and sanitation infrastructure.

PMID- 29471407
TI  - Plasma copeptin as a predictor of kidney disease.
AB  - Background: Plasma copeptin, a marker of vasopressin, is associated with renal
      function decline in the general population. Our aim was to study the links
      between elevated copeptin and future risk of kidney disease. Methods: Copeptin
      was measured in a sample of the Malmo Preventive Project (MPP) Reinvestigation (n
      = 5158) and in the Malmo Diet and Cancer Cardiovascular Cohort (MDC-CC) (n =
      5162). According to national registers, 89 subjects in MPP and 180 in MDC-CC
      developed chronic kidney disease (CKD) during follow-up (8.7 and 19.6 years,
      respectively). Results: After multivariate adjustment (gender, age, body mass
      index, smoking status, estimated glomerular filtration rate, prevalent diabetes,
      systolic blood pressure and prevalent antihypertensive treatment), copeptin (beta
      coefficient per 1 standard deviation increment of ln copeptin) was independently
      associated with increased risk of CKD during follow-up in both cohorts (MPP: (HR)
      1.46, 95% confidence interval (CI) 1.18-1.80, P < 0.001; MDC-CC: HR 1.25, 95% CI
      1.02-1.54, P = 0.03) among subjects free from prevalent kidney disease at
      baseline. Furthermore, in MPP, elevated copeptin predicted a specified diagnosis
      of kidney disease other than CKD (HR 1.31, 95% CI 1.08-1.59, P = 0.006) after
      multivariate adjustment. In a corresponding analysis in MDC-CC, copeptin was
      associated with a 10% increased risk, which, however, was non-significant (P =
      0.25). A meta-analysis of the MPP and MDC-CC data showed significant association
      between elevated copeptin and a specified diagnosis of kidney disease other than
      CKD (HR 1.18, 95% CI 1.05-1.34, P = 0.008). Conclusion: An increased level of
      copeptin independently predicts development of both CKD and other specified
      kidney diseases, suggesting that copeptin can be used to identify individuals at
      risk for kidney disease development.

PMID- 29471408
TI  - Thiazole derivatives act on virulence factors of Cryptococcus spp.
AB  - Cryptococcosis is an opportunistic or primary fungal infection considered to be
      the most prevalent fatal fungal disease worldwide. Owing to the limited number of
      available drugs, it is necessary to search for novel antifungal compounds. In the
      present work, we assessed the antifungal efficacy of three thiazole derivatives
      (1, 2, and 3). We conducted in vitro and in vivo assays to investigate their
      effects on important virulence factors, such as capsule and biofilm formation. In
      addition, the phagocytosis index of murine macrophages exposed to compounds 1, 2,
      and 3 and the in vivo efficacy of 1, 2, and 3 in Galleria mellonella infected
      with Cryptococcus spp. were evaluated. All compounds exhibited antifungal
      activity against biofilms and demonstrated a reduction in biofilm metabolic
      activity by 43-50% for C. gattii and 26-42% for C. neoformans. Thiazole compounds
      promoted significant changes in the capsule thickness of C. gattii compared to
      that of C. neoformans. Further examination of these compounds suggests that they
      can improve the phagocytosis process of peritoneal murine macrophages in vitro,
      causing an increase in the phagocytosis rate. Survival percentage was examined in
      the invertebrate model Galleria mellonella larvae, and only compound 3 could
      increase the survival at doses of 5 mg/kg after infection with C. gattii (P =
      .0001) and C. neoformans (P = .0007), similar to fluconazole at 10 mg/kg. The
      results demonstrated that thiazole compounds, mainly compound 3, have potential
      to be used for future studies in the search for new therapeutics for
      cryptococcosis.

PMID- 29471409
TI  - Innovation in the Treatment of Insomnia in Breast Cancer Survivors.

PMID- 29471410
TI  - Risk Factors Associated With Sustaining a Sport-related Concussion: An Initial
      Synthesis Study of 12,320 Student-Athletes.
AB  - Objective: The empirical identification of risk factors associated with sport
      related concussion (SRC) may improve the management of student-athletes. The
      current study attempted to identify and quantify bio-cognitive risk factors
      associated with sustaining a SRC. Methods: Cross-sectional ambispective study;
      level of evidence, 3. Neurocognitive testing of 12,320 middle school, high school
      and collegiate athletes was completed at preseason baseline and post-SRC.
      Univariate and multivariable logistic regressions were used to determine which
      pre-injury variables accurately predicted the occurrence of SRC. A quantitative
      risk score for each variable was developed. Results: Five of 13 variables
      maintained significance in the multivariable model with the associated weighted
      point scores: SRC history (21), prior headache treatment (6), contact sport (5),
      youth level of play (7), and history of ADHD/LD (2). Six stratified groups were
      formed based on probability of SRC, which produced an area under the curve (AUC)
      of 0.71 (95% CI 0.69-0.72, p < .001). Though the model was a significant
      predictor of SRC (X2 = 1,112.75, p < .001), the effect size was small and
      accounted for only 16% of the overall variance. Conclusions: An initial aggregate
      model of weighted bio-cognitive factors associated with increased odds of
      sustaining a SRC was developed. Previously validated factors were confirmed, yet
      a large source of variance remained unexplained. These findings emphasize the
      need to expand the host factors studied when assessing SRC risk, and that the
      existing, empirically based bio-cognitive factors do not adequately quantify the
      risk of SRC.

PMID- 29471411
TI  - Mechanisms Underpinning the Polypharmacy Effects of Medications in Psychiatry.
AB  - Background: Bipolar disorder is a mental health condition with progressive social
      and cognitive function disturbances. Most patients' treatments are based on
      polypharmacy, but with no biological basis and little is known of the drugs'
      interactions. The aim of this study was to analyze the effects of lithium,
      valproate, quetiapine, and lamotrigine, and the interactions between them, on
      markers of inflammation, bioenergetics, mitochondrial function, and oxidative
      stress in neuron-like cells and microglial cells. Methods: Neuron-like cells and
      lipopolysaccharide-stimulated C8-B4 cells were treated with lithium (2.5 mM),
      valproate (0.5 mM), quetiapine (0.05 mM), and lamotrigine (0.05 mM) individually
      and in all possible combinations for 24 h. Twenty cytokines were measured in the
      media from lipopolysaccharide-stimulated C8-B4 cells. Metabolic flux analysis was
      used to measure bioenergetics, and real-time PCR was used to measure the
      expression of mitochondrial function genes in neuron-like cells. The production
      of superoxide in treated cells was also assessed. Results: The results suggest
      major inhibitory effects on proinflammatory cytokine release as a therapeutic
      mechanism of these medications when used in combination. The various combinations
      of medications also caused overexpression of PGC1alpha and ATP5A1 in neuron-like
      cells. Quetiapine appears to have a proinflammatory effect in microglial cells,
      but this was reversed by the addition of lamotrigine independent of the drug
      combination. Conclusion: Polypharmacy in bipolar disorder may have
      antiinflammatory effects on microglial cells as well as effects on mitochondrial
      biogenesis in neuronal cells.

PMID- 29471412
TI  - Interactions between the concentration of non-starch polysaccharides in wheat and
      the addition of an enzyme mixture in a broiler digestibility and performance
      trial.
AB  - Two broiler trials were designed to investigate the relationship between the
      concentration of non-starch polysaccharides (NSP) in wheat and 1) its nutritional
      value for broilers and 2) the efficacy of exogenous enzymes. In a balance trial,
      diets were formulated with 3 wheat cultivars (Rustic and Viscount-medium NSP,
      Centenaire-high NSP) and were tested with or without the addition of an exogenous
      enzyme mixture. The diets were fed to 144 male Ross 308 broiler chickens housed
      in digestibility cages. Total tract nutrient digestibilities and AMEn were
      measured from 18 to 22 d of age. In a performance trial, diets were formulated
      with wheat (medium NSP diet) or with wheat mixed with rye and barley (high NSP
      diet) and were tested with or without the addition of an exogenous enzyme
      mixture. The diets were fed to 960 male Ross 308 broilers housed in pens and
      broiler performance during starter, grower and finisher periods was measured.In
      the balance trial, wheat cultivar did not affect nutrient digestibility or AMEn.
      Enzyme addition caused a significant increase in nutrient digestibilities and
      AMEn for the diet formulated with the high NSP wheat Centenaire only. In the
      performance trial, feeding the high NSP diet resulted in a higher feed conversion
      ratio and lower final body weight compared to the medium NSP diet. The largest
      improvements by enzyme addition were observed in the high NSP diet.In conclusion,
      the study was not able to show a consistent relationship between the NSP
      concentration of wheat and its nutritional value, but did demonstrate that the
      effect of an enzyme mixture on nutrient digestibility or broiler performance
      depends upon the NSP concentration in the diet.

PMID- 29471414
TI  - Examination of a Managed Pollinator Strategy for Almond Production Using Apis
      mellifera (Hymenoptera: Apidae) and Osmia lignaria (Hymenoptera: Megachilidae).
AB  - Pollination services provided by managed bees are essential for California almond
      (Prunus dulcis Mill.; Rosales: Rosaceae) production. Currently, pollination needs
      are met by rented or owned Apis mellifera L. (Hymenoptera: Apidae; honey bee)
      colonies. Excessive demand on a challenged A. mellifera industry to provide
      strong colonies in early spring has caused sharp increases in rental prices over
      the past decade, inviting the consideration of alternative pollinators in
      addition to, or in place of, A. mellifera. Osmia lignaria Say (Hymenoptera:
      Megachilidae; the blue orchard bee) is an excellent pollinator of fruit and nut
      trees, but its pollination impacts when used in tandem with A. mellifera have yet
      to be evaluated in commercial almond orchards. A 2-yr study was conducted in
      California orchards to compare almond pollination and production using A.
      mellifera as sole pollinator to an alternative practice of adding O. lignaria as
      a co-pollinator with A. mellifera. Almond orchard managerial decisions, such as
      for pesticide use and irrigation intensity, vary between almond growing regions
      because of local climates. Therefore, both north-central and southern sites of
      California's San Joaquin Valley are represented. We compared bee visitation, nut
      set, and nut yield between orchards and between tree rows within orchards. Also,
      O. lignaria reproductive success was recorded to assure that these bees remained
      in the orchards as pollinators and to assess the ability to sustain these bees
      under regional orchard conditions. We demonstrated that augmenting large
      commercial almond orchards with O. lignaria can significantly increase nut set
      and sometimes nut yield in both regions evaluated.

PMID- 29471413
TI  - Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI
      as a co-repressor for RUNX1.
AB  - SKI is a transcriptional co-regulator and overexpressed in various human tumors,
      for example in acute myeloid leukemia (AML). SKI contributes to the origin and
      maintenance of the leukemic phenotype. Here, we use ChIP-seq and RNA-seq analysis
      to identify the epigenetic alterations induced by SKI overexpression in AML
      cells. We show that approximately two thirds of differentially expressed genes
      are up-regulated upon SKI deletion, of which >40% harbor SKI binding sites in
      their proximity, primarily in enhancer regions. Gene ontology analysis reveals
      that many of the differentially expressed genes are annotated to hematopoietic
      cell differentiation and inflammatory response, corroborating our finding that
      SKI contributes to a myeloid differentiation block in HL60 cells. We find that
      SKI peaks are enriched for RUNX1 consensus motifs, particularly in up-regulated
      SKI targets upon SKI deletion. RUNX1 ChIP-seq displays that nearly 70% of RUNX1
      binding sites overlap with SKI peaks, mainly at enhancer regions. SKI and RUNX1
      occupy the same genomic sites and cooperate in gene silencing. Our work
      demonstrates for the first time the predominant co-repressive function of SKI in
      AML cells on a genome-wide scale and uncovers the transcription factor RUNX1 as
      an important mediator of SKI-dependent transcriptional repression.

PMID- 29471415
TI  - Blue and Black Cloth Targets: Effects of Size, Shape, and Color on Stable Fly
      (Diptera: Muscidae) Attraction.
AB  - Stable fly management is challenging because of the fly's dispersal behavior and
      its tendency to remain on the host only while feeding. Optically attractive traps
      have been used to survey and sometimes reduce adult populations. Insecticide
      treated blue and black cloth targets developed for tsetse fly management in
      Africa were found to be attractive to stable flies in the United States, and
      various evaluations were conducted in Louisiana and Florida. Tests using
      untreated targets were designed to answer questions about configuration, size,
      and color relative to efficacy and stability in high winds. Studies with electric
      grid targets and with targets paired with Olson traps showed cloth target color
      attraction in the following decreasing order: black > blue-black > blue. A solid
      black target is easier to make than a blue-black target because no sewing is
      involved. Attraction was not affected when flat 1-m2 targets were formed into
      cylinders, despite the limited view of the blue and black colors together. There
      was no reduction in attraction when the 1-m2 cylindrical targets were compared
      with smaller (63 * 30 cm high) cylindrical targets. In addition, there was no
      difference in attraction between the small blue-black, blue, and black targets.
      Significance of findings and implications of potential uses for treated targets
      are discussed. Target attraction was indicated by the numbers of stable flies
      captured on an Olson sticky trap placed 30 cm from the target. Although this
      system is adequate for field research, it greatly underestimates the actual
      numbers of stable flies attracted to treated targets.

PMID- 29471417
TI  - A study of circulating microRNAs identifies a new potential biomarker panel to
      distinguish aggressive prostate cancer.
AB  - Prostate cancer is one of the most common cancers in men worldwide. Currently
      available diagnostic and prognostic tools for this disease, such as prostate
      specific antigen, suffer from lack of specificity and sensitivity, resulting in
      over- and misdiagnosis. Hence, there is an urgent need for clinically relevant
      biomarkers capable of distinguishing between aggressive and nonaggressive forms
      of prostate cancer to aid in stratification, management and therapeutic
      decisions. To address this unmet need, we investigated the patterns of expression
      of a panel of 68 plasma-derived microRNAs (miRNAs) in a cohort of African
      American (AA) and European American (EA) prostate cancer patients (n = 114).
      miRNA qPCR results were analyzed using in-depth statistical methods, and a
      bioinformatics analysis was conducted to identify potential targets of the
      differentially expressed miRNAs. Our data demonstrate that a new previously
      unreported circulating miRNA signature consisting of a combination of interacting
      miRNAs (miR-17/miR-192) and an independent miRNA (miR-181a) are capable of
      segregating aggressive and nonaggressive prostate cancer in both AA and EA
      patients. The interacting miRNAs outperformed independent miRNAs in identifying
      aggressiveness. Our results suggest that these circulating miRNAs may constitute
      novel biomarkers of prostate cancer aggressiveness in both races and warrant
      further investigation.

PMID- 29471418
TI  - Skin-specific training experience of workers assessed for contact dermatitis.
AB  - Background: Contact dermatitis is a common and preventable work-related disease.
      Skin-specific training may be effective for preventing occupational contact
      dermatitis, but little information is available regarding actual workplace
      training and its effectiveness. Aims: To describe workplace skin-specific
      training among workers with suspected contact dermatitis. Methods: Patch test
      patients being assessed for suspected contact dermatitis at an occupational
      health clinic in Toronto, Canada, completed a questionnaire on training
      experiences, workplace characteristics, exposures and skin protection practices.
      Results: Of 175 patients approached, 122 (71%) workers completed questionnaires.
      Many (80%) had received general occupational health and safety and hazardous
      materials training (76%). Fewer (39%) received skin-specific training. Of those
      with work-related contact dermatitis, 52% did not receive skin-specific training.
      Skin-specific training was commonly provided by health and safety professionals
      or supervisors using video, classroom and online techniques. Content included
      glove use, exposure avoidance and hand washing information. Workers that received
      skin-specific training found it memorable (87%), useful (85%) and common sense in
      nature (100%). Conclusions: This study indicates gaps in workplace training on
      skin disease prevention for workers with contact dermatitis. Workers perceived
      skin-specific training to be useful. Understanding worker training experiences is
      important to prevention programme development and reducing work-related skin
      disease.

PMID- 29471416
TI  - Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with
      Behcet's disease: multicentre retrospective study.
AB  - Objective: To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of
      Behcet's disease (BD). Methods: Multicentre study of patients with BD-associated
      uveitis. Patients were refractory to conventional and biologic immunosuppressive
      drugs. The main outcome measures were intraocular inflammation, macular
      thickness, visual acuity and corticosteroid-sparing effects. Results: We studied
      11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was
      bilateral in nine patients. The patterns of ocular involvement were panuveitis (n
      = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior
      uveitis (n = 1). Cystoid macular oedema was present in seven patients. The
      clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients
      had received systemic corticosteroids, conventional immunosuppressants and the
      following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n
      = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or
      combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or
      162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations
      were present: oral and/or genital ulcers (n = 7), arthritis (n = 4),
      folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo
      reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and
      maintained improvement in all ocular parameters of the patients, with complete
      remission in eight of them. However, this was not the case for the extraocular
      manifestations, since TCZ was only effective in three of them. After a mean
      (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a
      severe infusion reaction and arthritis impairment, respectively. Conclusion: TCZ
      could be a therapeutic option in patients with BD and refractory uveitis.

PMID- 29471419
TI  - True-lumen and false-lumen diameter changes in the downstream aorta after frozen
      elephant trunk implantation.
AB  - OBJECTIVES: To evaluate early and mid-term clinical outcomes and to assess the
      potential of the frozen elephant trunk technique to induce remodelling of
      downstream aortic segments in acute and chronic thoracic aortic dissections.
      METHODS: Over a 4-year period, 65 patients (48 men, aged 61 +/- 12 years)
      underwent total aortic arch replacement using the frozen elephant trunk technique
      for acute (n = 31) and chronic (n = 34) thoracic aortic dissections at our
      institution. We assessed diameter changes at 3 levels: the L1 segment at the
      stent graft level; the L2 segment at the thoraco-abdominal transition level and
      the L3 segment at the coeliac trunk level. True-lumen (TL) and false-lumen (FL)
      diameter changes were assessed at each level. RESULTS: Fifty-six percent of
      patients had already undergone previous aortic or cardiac surgery. In-hospital
      mortality was 6%. Symptomatic spinal cord injury was not observed in this series.
      During a mean follow-up of 12 +/- 12 months, late death was observed in 6% of
      patients. Aortic reinterventions in downstream aortic segments were performed in
      28% at a mean of 394 +/- 385 days. TL expansion and FL shrinkage were measured in
      all segments and were observed at each level. This effect was the most pronounced
      at the level of the stent graft in patients with chronic aortic dissection, TL
      diameter increased from 15 +/- 17 mm before surgery to 28 +/- 2 mm (P = 0.001)
      after 2 years, and the FL diameter decreased from 40 +/- 11 mm before surgery to
      32 +/- 17 mm (P = 0.026). CONCLUSIONS: The frozen elephant trunk technique is
      associated with an excellent clinical outcome in a complex cohort of patients,
      and also effectively induces remodelling in downstream aortic segments in acute
      and chronic thoracic aortic dissections. The need for secondary interventions in
      downstream segments, which mainly depends on the extent of the underlying disease
      process, remains substantial. Further studies are required to assess the long
      term outcome of this approach.

PMID- 29471420
TI  - Ethics, effectiveness and population health information interventions: a Canadian
      analysis.
AB  - Population health information interventions (PHIIs) use information in efforts to
      promote health. PHIIs may push information to a target audience (communication),
      pull information from the public (surveillance), or combine both in a
      bidirectional intervention. Although PHIIs have often been framed as non-invasive
      and ethically innocuous, in reality they may be intrusive into people's lives,
      affecting not only their health but their senses of security, respect, and self
      determination. Ethical acceptability of PHIIs may have impacts on intervention
      effectiveness, potentially giving rise to unintended consequences. This article
      examines push, pull, and bidirectional PHIIs using empirical data from an
      ethnographic study of young mothers in Greater Vancouver, Canada. Data were
      collected from October 2013 to December 2014 via naturalistic observation and
      individual interviews with 37 young mothers ages 16-22. Transcribed interviews
      and field notes were analyzed using inductive qualitative thematic analysis. Both
      push and pull interventions were experienced as non-neutral by the target
      population, and implementation factors on a structural and individual scale
      affected intervention ethics and effectiveness. Based on our findings, we suggest
      that careful ethical consideration be applied to use of PHIIs as health promotion
      tools. Advancing the 'ethics of PHIIs' will benefit from empirical data that is
      informed by information and computer science theory and methods. Information
      technologies, digital health promotion services, and integrated surveillance
      programs reflect important areas for investigation in terms of their effects and
      ethics. Health promotion researchers, practitioners, and ethicists should explore
      these across contexts and populations.

PMID- 29471421
TI  - Class 3 semaphorins modulate the invasive capacity of rheumatoid arthritis
      fibroblast-like synoviocytes.
AB  - Objective: Class 3 semaphorins regulate diverse cellular processes relevant to
      the pathology of RA, including immune modulation, angiogenesis, apoptosis and
      invasive cell migration. Therefore, we analysed the potential role of class 3
      semaphorins in the pathology of RA. Methods: Protein and mRNA expression in RA
      synovial tissue, SF and fibroblast-like synoviocytes (FLS) were determined by
      immunoblotting and quantitative PCR (qPCR). RA FLS migration and invasion were
      determined using wound closure and transwell invasion assays, respectively.
      PlexinA1, neuropilin-1 and neuropilin-2 expression was knocked down using small
      interfering RNA (siRNA). Activation of FLS intracellular signalling pathways was
      assessed by immunoblotting. Results: mRNA expression of semaphorins (Sema)3B,
      Sema3C, Sema3F and Sema3G was significantly lower in the synovial tissue of early
      arthritis patients at baseline who developed persistent disease compared with
      patients with self-limiting disease after 2 years follow-up. Sema3B and Sema3F
      expression was significantly lower in arthritis patients fulfilling
      classification criteria for RA compared with those who did not. FLS expression of
      Sema3A was induced after stimulation with TNF, IL-1beta or lipopolysaccharides
      (LPS), while Sema3B and Sema3F expression was downregulated. Exogenously applied
      Sema3A induced the migration and invasive capacity of FLS, while stimulation with
      Sema3B or Sema3F reduced spontaneous FLS migration, and platelet-derived growth
      factor induced cell invasion, effects associated with differential regulation of
      MMP expression and mediated by the PlexinA1 and neuropilin-1 and -2 receptors.
      Conclusion: Our data suggest that modulation of class 3 semaphorin signaling
      could be a novel therapeutic strategy for modulating the invasive behaviour of
      FLS in RA.

PMID- 29471422
TI  - Phylogenetic analysis of Histoplasma capsulatum var duboisii in baboons from
      archived formalin-fixed, paraffin embedded tissues.
AB  - Histoplasma capsulatum var. duboisii (Hcd) infections have been well documented
      to cause chronic granulomatous disease, mainly involving the skin of baboons and
      humans in African countries primarily. This retrospective study classified the
      subspecies of Histoplasma and developed a phylogenetic tree utilizing DNA
      sequences extracted from formalin-fixed, paraffin embedded (FFPE) tissues from 9
      baboons from a research colony in Texas histologically diagnosed with Hcd. Based
      on sequence analysis of ITS-2, Tub-1, and ARF, Hcd isolated from the archived
      samples closely aligns with the African clade and has 88% sequence homology with
      a sample isolated from an individual in Senegal.

PMID- 29471423
TI  - Predictive Models of Cognitive Fatigue in Multiple Sclerosis.
AB  - Objective: Cognitive fatigue (CF) can be defined as decreased performance with
      sustained cognitive effort. The present study examined the interrelatedness of
      disease severity, fatigue, depression, and sleep quality in order to evaluate
      their predictive roles of CF in MS. Four theoretical models examining these
      variables were assessed. Methods: Fifty-eight individuals with a diagnosis of MS
      were recruited. CF was measured by examining last third versus first third
      performance on the Paced Auditory Serial Addition Test (PASAT). The PASAT and
      self-report measures of fatigue, depression, and sleep quality were administered.
      Path analysis was used to evaluate each of the models. Results: CF was correlated
      only with depression (r = .362, p = .006) and sleep quality (r = .433, p = .001).
      Sleep quality was the greatest significant independent predictor of CF (beta =
      .433, t(1,55) = 3.53, p < .001), accounting for 17.3% of the total variance. The
      best fitting model showed sleep quality as the largest contributor to CF;
      however, depression played a smaller predictive role. Furthermore, depression
      emerged as the strongest predictor of sleep quality and fatigue. Disease severity
      weakly predicted depression. Conclusions: Sleep quality is the most significant
      predictor of CF in MS. As such, sleep quality may be a treatable cause of CF.
      Sleep quality itself, however, accounted for only 17.3% of the variance in CF
      suggesting that other variables which were not formally assessed in this sample
      (e.g., anxiety, etc.) may also play a predictive role. Follow-up studies should
      evaluate how results may differ with a larger sample size.

PMID- 29471424
TI  - Predicting user adherence to behavioral eHealth interventions in the real world:
      examining which aspects of intervention design matter most.
AB  - Existing frameworks have identified a range of intervention design features that
      may facilitate adherence to eHealth interventions; however, empirical data are
      lacking on whether intervention design features can predict user adherence in the
      real world-where the public access available tools-and whether some design
      aspects of behavioral eHealth interventions are more important than others in
      predicting adherence. This study examined whether intervention design qualities
      predict user adherence to behavioral eHealth interventions in real-world use and
      which qualities matter the most. We correlated the online activities of users of
      30 web-based behavioral interventions-collected from a proprietary data set of
      anonymized logs from consenting users of Microsoft Internet Explorer add-on-with
      interventions' quality ratings obtained by trained raters prior to empirical
      examination. The quality ratings included: Usability, Visual Design, User
      Engagement, Content, Therapeutic Persuasiveness (i.e., persuasive design and
      incorporation of behavior change techniques), and Therapeutic Alliance. We found
      Therapeutic Persuasiveness (i.e., the incorporation of persuasive design/behavior
      change principles) to be the most robust predictor of adherence (i.e., duration
      of use, number of unique sessions; 40 <= rs <= .58, ps <= .005), explaining 42%
      of the variance in user adherence in our regression model. Results indicated up
      to six times difference in the percentage of users utilizing the interventions
      for more than a minimum amount of time and sessions based on Therapeutic
      Persuasiveness. Findings suggest the importance of persuasive design and behavior
      change techniques incorporation during the design and evaluation of digital
      behavioral interventions.

PMID- 29471426
TI  - Isolation, characterization, and antibiotic sensitivity assessment of
      Gallibacterium anatis biovar haemolytica, from diseased Egyptian chicken flocks
      during the years 2013 and 2015.
AB  - Gallibacterium anatis biovar haemolytica constitutes a part of the normal
      microflora in the upper respiratory and genital tracts of healthy chickens, but
      it is also associated with different pathological conditions. In the current
      study, 102 commercial chicken flocks suffering from respiratory disease and/or
      drop in egg production were investigated for the presence of G. anatis during
      2013 and 2015. These flocks comprised 8 breeder, 32 layer, and 62 broiler flocks.
      By culture method, 20 flocks were found positive: one isolate derived from
      broiler breeders, 6 isolates from layers, and 13 isolates from broilers. G.
      anatis biovar haemolytica was identified by phenotyping and PCR. Additionally,
      partial genome sequencing of 11 isolates (5 layer isolates of 2013 and 6 broiler
      isolates of 2015) based on 16S rRNA and 23S rRNA gene sequences was performed and
      revealed 96.5% to 100% genetic relatedness. Antibiotic sensitivity of these
      isolates revealed that the 2013 isolates were highly susceptible to florfenicol
      while the isolates of 2015 were highly susceptible to cefotaxime. Gallibacterium
      anatis biovar haemolytica is a newly introduced bacteria in Egypt causing
      salpingitis, peritonitis, drop in egg production, and/or respiratory signs.

PMID- 29471425
TI  - FOXL2C134W-Induced CYP19 Expression via Cooperation With SMAD3 in HGrC1 Cells.
AB  - Germline knockout studies in female mice demonstrated an essential role for
      forkhead box L2 (FOXL2) in early follicle development, whereas an inducible
      granulosa cell (GC)-specific deletion of Foxl2 in adults has shown ovary-to
      testis somatic sex reprogramming. In women, over 120 different germline mutations
      in the FOXL2 gene have been shown to cause blepharophimosis/ptosis/epicantus
      inversus syndrome associated with or without primary ovarian insufficiency. By
      contrast, a single somatic mutation (FOXL2C134W) accounts for almost all adult
      type GC tumors (aGCTs). To test the hypothesis that FOXL2C134W differentially
      regulates the expression of aGCT markers, we investigated the effect of
      FOXL2C134W on inhibin B and P450 aromatase expression using a recently
      established human GC line (HGrC1), which we now show to bear two normal alleles
      of FOXL2. Neither FOXL2wt nor FOXL2C134W regulate INHBB messenger RNA (mRNA)
      expression. However, FOXL2C134W selectively displays a 50-fold induction of CYP19
      mRNA expression dependent upon activin A. Mechanistically, the CYP19 promoter is
      activated in a similar way by FOXL2C134W interaction with SMAD3, but not by
      FOXL2wt. SMAD2 had no effect. Moreover, FOXL2C134W interactions with SMAD3 and
      with the FOX binding element located at -199 bp upstream of the ATG initiation
      codon of CYP19 are more sustainable than FOXL2wt. Thus, FOXL2C134W potentiates
      CYP19 expression in HGrC1 cells via enhanced recruitment of SMAD3 to a proximal
      FOX binding element. These findings may explain the pathophysiology of estrogen
      excess in patients with aGCT.

PMID- 29471427
TI  - Health and Work in Women and Men in the Welding and Electrical Trades: How Do
      They Differ?
AB  - Objectives: There is little information on how work tasks, demands, and exposures
      differ between women and men in nominally the same job. This is critical in
      setting workplace standards that will protect the health of both men and those
      women moving into less traditional work roles. Information used in setting
      standards is currently based almost entirely on male workers. This paper
      describes differences in work and health, and the relation between them, in women
      and men who have undergone the same trade training for the welding or electrical
      trades. Method: Four cohorts were established. Two were women across Canada in
      the welding and electrical trades who had been in an apprenticeship since 2005.
      Cohorts of men in the same trades during the same period were established in the
      province of Alberta, Canada. Participants completed a baseline questionnaire at
      recruitment and were followed up every 6 months to collect detailed information
      on work carried out and on their health and habits. At the end of the study (up
      to 5 years for women and up to 3 years for men), the cohort members completed a
      final questionnaire including questions on mental health, harassment, and gender.
      Results: The four cohorts comprised 1001 welders (447 female; 554 male) and 885
      in the electrical trades (438 female; 447 male). Follow-up information was
      available for 89%. Women were more likely than men to have had some post
      secondary education before starting their trade and were less likely to be living
      as married or to have a child. More welders smoked, and more men were heavy
      drinkers. At recruitment, more welders than those in the electrical trades
      reported rhinitis (sneezing and runny nose), depression, and anxiety. Female
      welders reported more depression (38%) than male welders (30%), compared to 24%
      in the electrical trades. At first follow-up, new-onset shoulder pain was more
      frequent in men and new-onset asthma or wheezing in welders. Within each trade,
      women reported less variety in tasks. Women welders were less likely to be
      employed in construction than men, and women were less likely to become
      industrial electricians. Overall, 54% of women and 46% of men reported never
      using respiratory protection when welding. In the end-of-study questionnaires
      received to date, 49% reported bullying or harassment during the apprenticeship,
      with higher proportions in welding than electrical trades and in women compared
      with men. Such harassment was reflected in higher anxiety and depression scores.
      Conclusions: This is the first report on these four cohorts and demonstrates the
      capacity for detailed analysis of the differences in exposure and new-onset
      occupationally related ill-health. While women and men in the same trades appear
      to be doing broadly similar work, and to have similar patterns on health at the
      first follow-up, there are some significant differences in the types of
      employment and variety of tasks. The very detailed information collected will
      allow more precise estimates of exposures to be correlated with health outcomes
      at the end of the follow-up period.

PMID- 29471428
TI  - Cognitive behavioural therapy for fear of falling and balance among older people:
      a systematic review and meta-analysis.
AB  - Background: fear of falling is prevalent among older people and associated with
      various health outcomes. A growing number of studies have examined the effects of
      interventions designed to reduce the fear of falling and improve balance among
      older people, yet our current understanding is restricted to physiological
      interventions. Psychological interventions such as cognitive behavioural therapy
      (CBT) have not been reviewed and meta-analysed. Objective: to perform a
      systematic review and meta-analysis evaluating the effects of CBT on reducing
      fear of falling and enhancing balance in community-dwelling older people. Method:
      randomised controlled trials (RCTs) addressing fear of falling and balance were
      identified through searches of six electronic databases, concurrent registered
      clinical trials, forward citation and reference lists of three previous
      systematic reviews. Results: a total of six trials involving 1,626 participants
      were identified. Four studies used group-based interventions and two adopted
      individual intervention. Intervention period ranged from 4 to 20 weeks, and the
      number and duration of face-to-face contact varied. Core components of the CBT
      intervention included cognitive restructuring, personal goal setting and
      promotion of physical activities. The risk of bias was low across the included
      studies. Our analysis suggests that CBT interventions have significant immediate
      and retention effects up to 12 months on reducing fear of falling, and 6 months
      post-intervention effect on enhancing balance. Conclusions: CBT appears to be
      effective in reducing fear of falling and improving balance among older people.
      Future researches to investigate the use of CBT on reducing fear of falling and
      improving balance are warranted.

PMID- 29471429
TI  - Comparison of 3 methods for estimating enteric methane and carbon dioxide
      emission in nonlactating cows.
AB  - Among techniques for estimating enteric methane (CH4) emission by ruminants, open
      circuit respiration chambers (OC), the use of a gas tracer (SF6), and the
      GreenFeed (GF) device are the most commonly used. In this study, we compared
      these techniques in 8 dry cows receiving a diet made of 70% hay and 30%
      concentrates given in limited and constant amounts, in a 15-wk experiment. Two
      periods in free stalls for SF6 and GF and in chambers for OC were used; in
      addition, SF6 was determined in chambers for 1 period. Methane emission (g/d) and
      CH4 yield (g/kg DMI) were higher (P < 0.0001) for OC than for SF6 and GF (367,
      310, and 319 g/d for OC, SF6, and GF, respectively). The difference between OC
      and GF was related to a difference in post-prandial rate of gas emission. The
      between-animal coefficient of variation of CH4 emission was higher for SF6 than
      for OC and GF (20.8, 13.5, and 12.0% on average, respectively). Correlation
      coefficients between OC and SF6 were high and significant for CH4 emission and
      CH4 yield (r = 0.782 and r = 0.717, respectively; P < 0.05), but not significant
      between OC and GF, or between SF6 and GF. Correlation coefficients were highly
      significant for SF6 determined either in free stalls or in chambers (r = 0.908
      and 0.903 for CH4 in g/d and g/kg DMI, respectively; P < 0.01). Carbon dioxide
      (CO2) emission and CO2 yield were similar for GF and OC (10,003 and 9,887 g/d,
      752 and 746 g/kg DMI, respectively); CO2 data obtained with SF6 were lower (7,718
      g/d and 606 g/kg DMI; P < 0.0001), but this technique is not relevant for CO2
      emission determination. Correlation coefficients between OC and GF were not
      significant for CO2 emission and CO2 yield. This set of results shows that
      differences between methods are minor for average values, but that individual
      correlations may limit their interchangeability for determining gas emissions of
      individual animals. This study also shows the reliability of GF on-farm
      determination of CH4 and CO2 emissions for groups of animals.

PMID- 29471430
TI  - GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12.
AB  - Colorectal cancer (CRC) is the fourth leading cause of cancer mortality
      worldwide. Genome-wide association studies (GWAS) identified more than 50 CRC
      loci. However, most of the previous studies were conducted in European
      population, and host genetic factors among Japanese population are largely
      remained to be identified. To identify novel loci in the Japanese population,
      here, we performed a large-scale GWAS using 6692 cases and 27 178 controls
      followed by a replication analysis using more than 11 000 case-control samples.
      We found the significant association of 10 loci (P < 5 * 10-8), including 2 novel
      loci on 16q24.1 (IRF8-FOXF1, rs847208, P = 3.15 * 10-9 and odds ratio = 1.107
      with 95% confidence interval (CI) of 1.071-1.145) and 20q13.12 (TOX2, rs6065668,
      P = 4.47 * 10-11 and odds ratio = 0.897 with 95% CI of 0.868-0.926). Moreover, 35
      previously reported single nucleotide polymorphisms (SNPs) in 24 regions were
      validated in the Japanese population (P < 0.05) with the same risk allele as in
      the previous studies. SNP rs6065668 was significantly associated with TOX2
      expression in the sigmoid colon. In addition, nucleotide substitutions in the
      regulatory region of TOX2 were predicted to alter the binding of several
      transcription factors, including KLF5. Our findings elucidate the important role
      of genetic variations in the development of CRC in the Japanese population.

PMID- 29471431
TI  - Making Waves: New Developments in Toxicology With the Zebrafish.
AB  - The laboratory zebrafish (Danio rerio) is now an accepted model in toxicologic
      research. The zebrafish model fills a niche between in vitro models and mammalian
      biomedical models. The developmental characteristics of the small fish are
      strategically being used by scientists to study topics ranging from high
      throughput toxicity screens to toxicity in multi- and transgenerational studies.
      High-throughput technology has increased the utility of zebrafish embryonic
      toxicity assays in screening of chemicals and drugs for toxicity or effect.
      Additionally, advances in behavioral characterization and experimental
      methodology allow for observation of recognizable phenotypic changes after
      xenobiotic exposure. Future directions in zebrafish research are predicted to
      take advantage of CRISPR-Cas9 genome editing methods in creating models of
      disease and interrogating mechanisms of action with fluorescent reporters or
      tagged proteins. Zebrafish can also model developmental origins of health and
      disease and multi- and transgenerational toxicity. The zebrafish has many
      advantages as a toxicologic model and new methodologies and areas of study
      continue to expand the usefulness and application of the zebrafish.

PMID- 29471432
TI  - Effectiveness of 7- and 13-Valent Pneumococcal Conjugate Vaccines in a Schedule
      Without a Booster Dose: A 10-Year Observational Study.
AB  - Background: Unique among high-income countries, Australia has used a 3 + 0
      schedule (3 primary doses, no booster) for infant pneumococcal conjugate vaccine
      (PCV) since January 2005, initially 7 valent (PCV7) then 13 valent (PCV13) from
      July 2011. We measured vaccine effectiveness (VE) of both PCVs against invasive
      pneumococcal disease (IPD) using 2 methods. Methods: Cases were IPD notifications
      to the national surveillance system of children eligible for respective PCVs. For
      case-control method, up to 10 age-matched controls were derived from the
      Australian Childhood Immunisation Register. For indirect cohort method, controls
      were IPD cases due to serotypes not in PCVs. VE was calculated as (1 - odds ratio
      [OR]) * 100 by logistic regression. VE waning was estimated as odds of vaccine
      type (VT) IPD in consecutive 12-month periods post-dose 3. Results: Between 2005
      and 2014, there were 1209 and 308 IPD cases in PCV7-eligible and PCV13-eligible
      cohorts, respectively. Both methods gave comparable VE estimates. In infants, VE
      for 3 doses against VT IPD was 92.9% (95% confidence interval [CI], 27.7% to
      99.3%) for PCV7 and 86.5% (95% CI, 11.7% to 97.9%) for PCV13. From 12 months post
      dose 3, the odds of VT IPD by 24-36 months increased significantly for PCV7 (5.6,
      95% CI, 1.2-25.4) and PCV13 (5.9, 95% CI, 1.0-35.2). Conclusions: For both PCVs
      in a 3 + 0 schedule, despite similar VE, progressive increase in breakthrough
      cases only occurred post-PCV13. This supports the importance of a booster dose of
      PCV13 in the second year of life to maintain protection.

PMID- 29471433
TI  - Reply to Godbole et al.

PMID- 29471434
TI  - Disease Definition for Schizophrenia by Functional Connectivity Using Radiomics
      Strategy.
AB  - Specific biomarker reflecting neurobiological substrates of schizophrenia (SZ) is
      required for its diagnosis and treatment selection of SZ. Evidence from
      neuroimaging has implicated disrupted functional connectivity in the
      pathophysiology. We aimed to develop and validate a method of disease definition
      for SZ by resting-state functional connectivity using radiomics strategy. This
      study included 2 data sets collected with different scanners. A total of 108
      first-episode SZ patients and 121 healthy controls (HCs) participated in the
      current study, among which 80% patients and HCs (n = 183) and 20% (n = 46) were
      selected for training and testing in intra-data set validation and 1 of the 2
      data sets was selected for training and the other for testing in inter-data set
      validation, respectively. Functional connectivity was calculated for both groups,
      features were selected by Least Absolute Shrinkage and Selection Operator (LASSO)
      method, and the clinical utility of its features and the generalizability of
      effects across samples were assessed using machine learning by training and
      validating multivariate classifiers in the independent samples. We found that the
      accuracy of intra-data set training was 87.09% for diagnosing SZ patients by
      applying functional connectivity features, with a validation in the independent
      replication data set (accuracy = 82.61%). The inter-data set validation further
      confirmed the disease definition by functional connectivity features (accuracy =
      83.15% for training and 80.07% for testing). Our findings demonstrate a valid
      radiomics approach by functional connectivity to diagnose SZ, which is helpful to
      facilitate objective SZ individualized diagnosis using quantitative and specific
      functional connectivity biomarker.

PMID- 29471435
TI  - Immune Infiltration in Invasive Lobular Breast Cancer.
AB  - Background: Invasive lobular breast cancer (ILC) is the second most common
      histological subtype of breast cancer after invasive ductal cancer (IDC). Here,
      we aimed at evaluating the prevalence, levels, and composition of tumor
      infiltrating lymphocytes (TILs) and their association with clinico-pathological
      and outcome variables in ILC, and to compare them with IDC. Methods: We
      considered two patient series with TIL data: a multicentric retrospective series
      (n = 614) and the BIG 02-98 study (n = 149 ILC and 807 IDC). We compared immune
      subsets identified by immuno-histochemistry in the ILC (n = 159) and IDC (n =
      468) patients from the Nottingham series, as well as the CIBERSORT immune
      profiling of the ILC (n = 98) and IDC (n = 388) METABRIC and The Cancer Genome
      Atlas patients. All ILC/IDC comparisons were done in estrogen receptor (ER)
      positive/human epidermal growth factor receptor 2 (HER2)-negative tumors. All
      statistical tests were two-sided. Results: TIL levels were statistically
      significantly lower in ILC compared with IDC (fold-change = 0.79, 95% confidence
      interval = 0.70 to 0.88, P < .001). In ILC, high TIL levels were associated with
      young age, lymph node involvement, and high proliferative tumors. In the
      univariate analysis, high TIL levels were associated with worse prognosis in the
      retrospective and BIG 02-98 lobular series, although they did not reach
      statistical significance in the latter. The Nottingham series revealed that the
      levels of intratumoral but not total CD8+ were statistically significantly lower
      in ILC compared with IDC. Comparison of the CIBERSORT profiles highlighted
      statistically significant differences in terms of immune composition.
      Conclusions: This study shows differences between the immune infiltrates of ER
      positive/HER2-negative ILC and IDC in terms of prevalence, levels, localization,
      composition, and clinical associations.

PMID- 29471438
TI  - Development of a health assessment instrument for people with intellectual
      disabilities: a Delphi study.
AB  - Background: People with intellectual disabilities (IDs) experience health
      inequalities. Applying health assessments is one way of diminishing these
      inequalities. A health assessment instrument can support general practitioners
      (GPs) in providing better medical care to people with ID. Objectives: The aim of
      this study was to determine which items should be part of a health assessment
      instrument for people with ID to be used in primary care. Methods: This Delphi
      consensus study was conducted among 24 GP experts and 21 ID physicians. We
      performed three anonymous sequential online questionnaire rounds. We started with
      82 'general' items and 14 items concerning physical and additional examinations
      derived from the international literature and a focus group study among Dutch
      GPs. We definitely included items if more than 75% of the GP experts agreed on
      their inclusion. Results: The participation rate in all rounds was above 88%. The
      expert groups proposed 10 new items. Consensus was reached on 64 'general' items
      related to highly prevalent diseases, public health and health promotion.
      Consensus was also reached on 18 physical and additional examination items.
      Conclusions: For the first time, experts in a Delphi study were able to arrive at
      a selection of items for a health assessment instrument for people with ID. The
      overall agreement among the GPs and ID physicians was good. Because the experts
      prefer that patients complete the health assessment questionnaire at home,
      questions that cover these items must be formulated clearly.

PMID- 29471436
TI  - Antiandrogen Treatment Ameliorates Reproductive and Metabolic Phenotypes in the
      Letrozole-Induced Mouse Model of PCOS.
AB  - Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of
      reproductive age, is characterized by hyperandrogenism, anovulation, and
      polycystic ovaries. Although its etiology is unknown, excess androgens are
      thought to be a critical factor driving the pathology of PCOS. We previously
      demonstrated that continuous exposure to the aromatase inhibitor letrozole (LET)
      in mice produces many hallmarks of PCOS, including elevated testosterone (T) and
      luteinizing hormone, anovulation, and obesity. In the current study, we sought to
      determine whether androgen receptor (AR) actions are responsible for any of the
      phenotypes observed in LET mice. C57BL/6 female mice were subcutaneously
      implanted with LET or placebo control and subsequently treated with the
      nonsteroidal AR antagonist flutamide or vehicle control. Flutamide treatment in
      LET females reversed elevated T levels and restored ovarian expression of Cyp17a1
      (critical for androgen synthesis) to normal levels. Pituitary expression of Lhb
      was decreased in LET females that received flutamide treatment, with no changes
      in expression of Fshb or Gnrhr. Flutamide treatment also restored estrous cycling
      and reduced the number of ovarian cyst-like follicles in LET females.
      Furthermore, body weight and adipocyte size were decreased in flutamide-treated
      LET females. Altogether, our findings provide strong evidence that AR signaling
      is responsible for many key reproductive and metabolic PCOS phenotypes and
      further establish the LET mouse model as an important tool for the study of
      androgen excess.

PMID- 29471439
TI  - Robot-assisted ligation of bronchial artery could be an alternative to
      embolization.
AB  - A 37-year-old patient presented with a self-limiting episode of moderate
      haemoptysis. Contrast-enhanced chest computed tomography showed a tortuous and
      dilated right bronchial artery arising from the descending aorta at the level of
      T6. Therapeutic angiography was attempted, but in the presence of spinal artery
      arising from the bronchial artery in question, selective embolization was
      contraindicated due to risk of spinal cord ischaemia. After a multidisciplinary
      meeting, it was decided to attempt surgery to ligate this pathological artery. We
      performed minimally invasive robot-assisted ligation of this pathological artery.
      The postoperative course was uneventful with good clinical and radiological
      outcome at 3-month follow-up. A minimally invasive approach provides a real
      alternative to embolization and could be a therapeutic option.

PMID- 29471437
TI  - Cerebellar BDNF Promotes Exploration and Seeking for Novelty.
AB  - Background: Approach system considered a motivational system that activates
      reward-seeking behavior is associated with exploration/impulsivity, whereas
      avoidance system considered an attentional system that promotes inhibition of
      appetitive responses is associated with active overt withdrawal. Approach and
      avoidance dispositions are modulated by distinct neurochemical profiles and
      synaptic patterns. However, the precise working of neurons and trafficking of
      molecules in the brain activity predisposing to approach and avoidance are yet
      unclear. Methods: In 3 phenotypes of inbred mice, avoiding, balancing, and
      approaching mice, selected by using the Approach/Avoidance Y-maze, we analyzed
      endogenous brain levels of brain derived neurotrophic factor, one of the main
      secretory proteins with pleiotropic action. To verify the effects of the acute
      increase of brain derived neurotrophic factor, balancing and avoiding mice were
      bilaterally brain derived neurotrophic factor-infused in the cortical cerebellar
      regions. Results: Approaching animals showed high levels of explorative behavior
      and response to novelty and exhibited higher brain derived neurotrophic factor
      levels in the cerebellar structures in comparison to the other 2 phenotypes of
      mice. Interestingly, brain derived neurotrophic factor-infused balancing and
      avoiding mice significantly increased their explorative behavior and response to
      novelty. Conclusions: Cerebellar brain derived neurotrophic factor may play a
      role in explorative and novelty-seeking responses that sustain the approach
      predisposition.

PMID- 29471440
TI  - Spotlight on recently published ICVTS articles.

PMID- 29471441
TI  - Retraction to 'Functional results after chest wall stabilization with a new
      screwless fixation device' [Eur J Cardiothorac Surg 2015;47:868-75].

PMID- 29471442
TI  - Estimation of adaptive ventilation success and failure using polysomnogram and
      outpatient therapy biomarkers.
AB  - Study Objectives: Adaptive servo-ventilation (ASV) devices provide anticyclic
      pressure support for the treatment of central and/or complex sleep apnea,
      including heart failure patients. Variability in responses in the clinic and
      negative clinical trials motivated assessment of standard and novel signal
      biomarkers for ASV efficacy. Methods: Multiple clinical databases were queried to
      assess potential signal biomarkers of ASV effectiveness, including the following:
      (1) attended laboratory adaptive ventilation titrations: 108, of which 66 had
      mainstream ETCO2 measurements; (2) AirView data in 98 participants, (3) complete
      data, from diagnostic polysomnogram (PSG) through review and prospective analysis
      of on-therapy data using SleepyHead freeware in 44 participants; and (4)
      hemodynamic data in the form of beat-to-beat blood pressure during ASV titration,
      using a Finometer in five participants. Results: Signal biomarkers of reduced ASV
      efficacy were noted as follows: (1) an arousal index which markedly exceeded the
      respiratory event index during positive pressure titration; (2) persistent
      pressure cycling during long-term ASV therapy, visible in online review systems
      or reviewing data using freeware; (3) the ASV-associated pressure cycling induced
      arousals, sleep fragmentation, and blood pressure surges; and (4) elevated ratios
      of 95th percentile to median tidal volume, minute ventilation, and respiratory
      rate were associated with pressure cycling. High intraclass coefficients (>0.8)
      for machine apnea-hypopnea index and other extractable metrics were consistent
      with stability of patterns over multiple nights of use. Global clinical outcomes
      correlated negatively with pressure cycling. Conclusions: Potential
      polysomnographic- and device-related signal biomarkers of ASV efficacy are
      described and may allow improved estimation of therapeutic effectiveness of
      adaptive ventilation.

PMID- 29471443
TI  - Immunomodulatory potential of dietary soybean-derived isoflavones and saponins in
      pigs.
AB  - In this review, the potential for use of soy-derived bioactive compounds as
      immunomodulatory feed additives in pigs is discussed. Soy is a major component of
      the modern U.S. swine diet in today's commercial industry, providing the bulk of
      dietary AA necessary for growth and production. However, soy use has generally
      been limited in early growth phases, during which the risks of immunological
      insult and disease are among the highest. Improvements of soybean processing and
      development of soy protein products with little to no antinutritional factors
      have made soy more appropriate for use in young pigs but additional processing
      may affect bioactive compound levels in the feed. The bioactive compounds of
      interest for this review are soy isoflavones and soy saponins. Soy isoflavones
      are flavonoid compounds with a range of biological activity including moderate
      estrogenic effects at low biological concentrations. Although estrogenic effects
      are of more interest in human medical research, isoflavones are also known for
      their anti-inflammatory, antioxidative properties at cellular levels, engaging
      several receptors and pathways including inhibition of NF-kappaB activation and
      inducible-nitric oxide synthase enzymes, thereby ascribing antiviral properties.
      Saponins, amphipathic glycoside compounds, also engage anti-inflammatory
      pathways, though their biological activity in pigs has not been well investigated
      and seem to mainly be observed on the mucous membrane in the gastrointestinal
      tract. Regarding use as an immunomodulatory feed additive, supplemental soy
      isoflavones have been shown to improve immunological status of pigs and produce
      mild improvements of growth performance under certain disease challenges
      including porcine reproductive and respiratory syndrome virus. Although more in
      vivo research in pigs is needed to fully understand biological activity of these
      compounds in the live animal, soy-derived bioactive compounds show great
      potential as a health promoting feed additive for the modern swine industry.

PMID- 29471444
TI  - Relation of Sex Hormone Levels With Prevalent and 10-Year Change in Aortic
      Distensibility Assessed by MRI: The Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Women experience a steeper decline in aortic elasticity related to
      aging compared to men. We examined whether sex hormone levels were associated
      with ascending aortic distensibility (AAD) in the Multi-Ethnic Study of
      Atherosclerosis. METHODS: We studied 1,345 postmenopausal women and 1,532 men
      aged 45-84 years, who had serum sex hormone levels, AAD measured by phase
      contrast cardiac magnetic resonance imaging, and ejection fraction>50% at
      baseline. Among these participants, 457 women and 548 men returned for follow-up
      magnetic resonance imaging 10-years later. Stratified by sex, and using mixed
      effects linear regression methods, we examined associations of sex hormones (as
      tertiles) with baseline and annual change in log-transformed AAD (mm Hg-110-3),
      adjusting for demographics, body size, lifestyle factors, mean arterial pressure,
      heart rate, hypertensive medication use (and in women, for hormone therapy use
      and years since menopause). RESULTS: The mean (SD) age was 65 (9) for women and
      62 (10) years for men. AAD was lower in women than men (P < 0.001). In adjusted
      cross-sectional analysis, the highest tertile of free testosterone (compared to
      lowest) in women was significantly associated with lower AAD [-0.10 (-0.19, 
      0.01)] and the highest tertile of estradiol in men was associated with greater
      AAD [0.12 (0.04, 0.20)]. There were no associations of sex hormones with change
      in AAD over 10 years, albeit in a smaller sample size. CONCLUSIONS: Lower free
      testosterone in women and higher estradiol in men were associated with greater
      aortic distensibility at baseline, but not longitudinally. Sex hormone levels may
      account for differences in AAD between women and men.

PMID- 29471445
TI  - Does Soil Treated with Conidial Formulations of Trichoderma spp. Attract or Repel
      Subterranean Termites?
AB  - Previous studies showed that many wood-rotting fungi were attractive to termites;
      however, little attention has been paid to the relationship between termites and
      soil fungus. In the present study, different designs of two-choice tests were
      conducted to investigate the behaviors of two subterranean termites, Coptotermes
      formosanus Shiraki (wood-feeding lower termites) and Odontotermes formosanus
      (Shiraki) (fungus-growing higher termites), in response to soil (or sand) treated
      with the commercial conidial formulations of Trichoderma harzianum Rifai
      (BioWorks) and Trichoderma viride Pers. ex Fries (Shuiguxin). The short-term (1
      d) choice tests showed no significant difference in termite aggregation (C.
      formosanus and O. formosanus) between treated and untreated soil, regardless of
      Trichoderma species and concentrations. However, in the long-term choice tests,
      C. formosanus consumed significantly more wood in the chambers containing soil
      treated with the conidial formulation of T. viride (1 * 108 conidia/g) than that
      containing untreated soil. The tunneling choice tests showed that sand treated
      with T. viride (1 * 106 or 1 * 108 conidia/g) or T. harzianum (1 * 106 conidia/g)
      significantly increased the tunneling activities of C. formosanus. However, sand
      treated with T. viride (1 * 106 or 1 * 108 conidia/g) had a repellent effect on
      O. formosanus. Our study showed that the two subterranean termites behaved
      differently when responding to the conidial formulations of Trichoderma.

PMID- 29471447
TI  - Corrigendum.

PMID- 29471446
TI  - Simultaneous care in neuro-oncology.

PMID- 29471448
TI  - The CBTRUS story: providing accurate population-based statistics on brain and
      other central nervous system tumors for everyone.

PMID- 29471449
TI  - Obesity associated advanced glycation end products within the human uterine
      cavity adversely impact endometrial function and embryo implantation competence.
AB  - STUDY QUESTION: Do obese levels of advanced glycation end products (AGEs) within
      the uterine cavity detrimentally alter tissue function in embryo implantation and
      placental development? SUMMARY ANSWER: Obese levels of AGEs activate inflammatory
      signaling (p65 NFkappaB) within endometrial epithelial cells and alter their
      function, cause endoplasmic reticulum (ER) stress in endometrial stromal cells
      and impair decidualization, compromise implantation of blastocyst mimics and
      inhibit trophoblast invasion. WHAT IS KNOWN ALREADY: Obese women experience a
      higher incidence of infertility, recurrent miscarriage and pregnancy
      complications compared with lean women. Oocyte donation cycles suggest a
      detrimental uterine environment plays a role in these outcomes. STUDY DESIGN,
      SIZE, DURATION: Uterine lavage and tissues from lean (BMI 19.5-24.9, n = 17) and
      obese (BMI > 30, n = 16) women examined. Cell culture experiments utilizing human
      endometrial epithelial, trophectoderm and trophoblast cell lines and primary
      human stromal cells used to examine the functional impact of obese levels of
      AGEs. PARTICIPANTS/MATERIALS, SETTING, METHODS: Levels of AGEs examined within
      uterine lavage assessed by ELISA to determine differences between lean and obese
      women. Expression and localization of AGEs, receptor for AGEs (RAGE) and NFkappaB
      within endometrial tissues obtained from lean and obese women determined by
      immunohistochemistry. Endometrial epithelial cells (ECC-1), primary human stromal
      cells and trophoblast cells (HTR8-SVneo) treated with lean (2000 nmol/mol lysine)
      or obese (8000 nmol/mol lysine) uterine levels of AGEs and p65 NFkappaB (western
      immunoblot), real-time adhesion, proliferation migration and invasion
      (xCelligence real-time cell function analysis), decidualization (cell morphology
      and prolactin release), ER stress (western immunoblot for p-PERK) determined. Co
      cultures of endometrial epithelial cells and blastocyst mimics (trophectoderm
      spheroids) similarly treated with lean or obese uterine levels of AGEs to
      determine their impact on embryo implantation. MAIN RESULTS AND THE ROLE OF
      CHANCE: AGEs were significantly elevated (P = 0.004) within the obese (6503.59
      MUmol/mol lysine) versus lean (2165.88 MUmol/mol lysine) uterine cavity (uterine
      lavage) with increased immunostaining for AGEs, RAGE and NFkB within obese
      endometrial tissues during the proliferative phase of the menstrual cycle. Obese
      uterine levels of AGEs inhibited adhesion and proliferation of endometrial
      epithelial (ECC-1) cells compared to treatment with lean uterine levels of AGEs.
      Obese uterine AGE levels impacted primary human endometrial stromal cell
      decidualization and activated ER stress within these cells. Obese uterine levels
      of AGEs also inhibited trophectodermal spheroid adhesion to hormonally primed
      endometrial epithelial cells and trophoblast cell line HTR8/SV-neo invasion.
      LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Mechanistic studies are
      performed in vitro and may not completely recapitulate cell function in vivo.
      WIDER IMPLICATIONS OF THE FINDINGS: These data corroborate clinical data
      suggesting the presence of an altered uterine environment in obese women and
      demonstrate that elevated uterine levels of AGEs within these women may
      detrimentally impact endometrial function, embryo implantation and placental
      development. Uterine AGE assessment in infertility work up may prove useful in
      determining underlying causes of infertility. AGEs can be targeted
      pharmacologically and such treatments may prove effective in improving
      reproductive complications experience by obese women. STUDY FUNDING/COMPETING
      INTEREST(S): Supported by NHMRC Fellowship (#1002028 to L.A.S.), and the
      Victorian Government's Operational Infrastructure Support Program. MTC is
      supported by a JDRF Australia Clinical Research Network Career Development Award.
      The authors have declared that no conflict of interest exists.

PMID- 29471450
TI  - Stage-Dependent Expression of Deltamethrin Toxicity and Resistance in Triatoma
      infestans (Hemiptera: Reduviidae) From Argentina.
AB  - Triatoma infestans Klug (Hemiptera: Reduviidae) is the main vector of Chagas
      disease in Latin America. This insect has been controlled with pyrethroids since
      the 1980s, although the emergence of resistance to deltamethrin has decreased
      control success in some areas of the Gran Chaco ecoregion. The response of T.
      infestans to deltamethrin was evaluated per developmental stage. In addition, we
      evaluated the possible stage-dependent expression of deltamethrin resistance. The
      bioassays were conducted by topical application of the insecticide in acetone.
      The drop size, age at the time of exposure, and mortality measuring time were
      standardized per stage. The lethal dose of deltamethrin moderately increased with
      the developmental stage. The resistance to deltamethrin was expressed in every
      instar, and was the highest in the fourth- and fifth-instar nymphs. While
      increasing, weight plays a relevant role in lethal dose stage dependency, a
      number of contributing factors such as degradative metabolism are probably
      involved in the variability of insecticide effect and resistance described for
      different T. infestans developmental stages. Possible explanations for these
      differences and their implications on resistance management and chemical control
      are discussed.

PMID- 29471451
TI  - Genomic Evidence of Widespread Admixture from Polar Bears into Brown Bears during
      the Last Ice Age.
AB  - Recent genomic analyses have provided substantial evidence for past periods of
      gene flow from polar bears (Ursus maritimus) into Alaskan brown bears (Ursus
      arctos), with some analyses suggesting a link between climate change and genomic
      introgression. However, because it has mainly been possible to sample bears from
      the present day, the timing, frequency, and evolutionary significance of this
      admixture remains unknown. Here, we analyze genomic DNA from three additional and
      geographically distinct brown bear populations, including two that lived
      temporally close to the peak of the last ice age. We find evidence of admixture
      in all three populations, suggesting that admixture between these species has
      been common in their recent evolutionary history. In addition, analyses of ten
      fossil bears from the now-extinct Irish population indicate that admixture peaked
      during the last ice age, whereas brown bear and polar bear ranges overlapped.
      Following this peak, the proportion of polar bear ancestry in Irish brown bears
      declined rapidly until their extinction. Our results support a model in which ice
      age climate change created geographically widespread conditions conducive to
      admixture between polar bears and brown bears, as is again occurring today. We
      postulate that this model will be informative for many admixing species pairs
      impacted by climate change. Our results highlight the power of paleogenomics to
      reveal patterns of evolutionary change that are otherwise masked in contemporary
      data.

PMID- 29471452
TI  - Protecting the Community Through Child Vaccination.
AB  - The direct impact of vaccines on children is well described, but the major public
      health impact of indirect protection provided to the community by vaccines is
      underappreciated. Community protection occurs when vaccinated persons block the
      chain of transmission, protecting undervaccinated or unvaccinated susceptible
      community members by preventing exposure and limiting the spread of the pathogen
      through the community. Substantial declines in disease incidence have occurred
      shortly after implementing new childhood vaccines, including declines among
      vaccine-ineligible children, adolescents, and adults. Protection of susceptible
      community members depends on maintaining high vaccination rates. Improved
      recognition of community protection will strengthen childhood vaccination
      strategies that will protect our communities into the future.

PMID- 29471453
TI  - Modified Minimally Invasive Transforaminal Lumbar Interbody Fusion Technique Can
      Potentially Improve Safety of Interbody Graft Placement.
AB  - BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MITLIF) is
      a well-described procedure with excellent reported outcomes. A modification of
      interbody graft placement can potentially improve the ease and safety of this
      procedure. OBJECTIVE: To describe a modification of the MITLIF graft placement
      and retrospectively review our experience including intraoperative and
      postoperative complications. METHODS: Single surgeon, single institution,
      retrospective analysis of consecutive patients who underwent a modified MITLIF
      technique between November 2011 and December 2013. Hospital records including
      operative notes and discharge summaries were reviewed for patient demographics,
      surgical parameters including operative time and estimated blood loss,
      intraoperative complications including durotomy/cerebrospinal fluid leak, and
      postoperative outcomes including time before ambulation and length of stay were
      all reviewed and analyzed. RESULTS: Eighty-three consecutive MITLIF patients; 71
      underwent 1-level fusion and 12 had multilevel fusions. Average operative time
      for single level was 181 min; multilevel was 323 min. Average estimated blood
      loss was 140 mL. Time before ambulation was <1 d, average length of stay was 1.6
      d. There were a total of 4 complications in this series (4.8%). There was zero
      incidence of durotomy or cerebrospinal fluid leak. CONCLUSION: This modified
      MITLIF technique of maintaining the medial facet prior to discectomy and
      interbody graft placement can offer the minimally invasive spine surgeons
      increased assurance while placing the graft and potentially enhance the overall
      safety and efficacy of this approach. Surgeons utilizing this approach will have
      little difficulty utilizing this slight modification.

PMID- 29471454
TI  - The Impact of Using Different Reference Populations on Measurement of Breast
      Cancer-Related Cognitive Impairment Rates.
AB  - Objective: To evaluate how use of different reference populations affects
      estimates of breast cancer-related cognitive impairment rates. Methods: Patients
      aged >=60 years with stage 0-3 breast cancer (n = 371) and matched non-cancer
      controls (n = 370) completed 13 neuropsychological tests prior to systemic
      therapy or at enrollment (controls). The tests captured three domains: attention,
      processing speed and executive function; learning and memory; and visual-spatial
      function. Domain-specific impairment was defined as having one test score 2 SD
      below or two or more test scores 1.5 SD below the reference population means.
      Different reference populations were used to define impairment: published
      normative data, study-specific controls, age and education-stratified controls,
      and age and education-adjusted controls. The associations between the resultant
      impairment rates and breast cancer (vs. control) were evaluated using chi-square
      tests and logistic regression models. Cohen's kappa coefficients were used to
      evaluate agreement of impairment rates between study-specific control performance
      and the other reference population groups. Results: The patients and controls
      were aged 68.0 (SD 6.0) and 67.9 (SD 7.0) years, respectively. The association of
      breast cancer-control status with impairment did not differ based on reference
      group. Cognitive impairment based on published normative data yielded less
      agreement on impairment rates (kappa = 0.22-0.89) than study-specific age and
      education-stratified control performance (kappa = 0.62-1.00). Conclusion: The
      choice of reference populations did not affect conclusions about the association
      of cognition with breast cancer. However, while study-specific reference
      populations provided greater internal consistency in defining cognitive
      impairment, benchmarking against published normative data will enhance the
      ability to compare results across studies.

PMID- 29471455
TI  - Chemical composition, energy, and amino acid digestibility in 7 cottonseed co
      products fed to growing pigs.
AB  - The objective of this study was to determine the chemical composition, DE and ME
      contents, and apparent ileal digestibility (AID) and standardized ileal
      digestibility (SID) of AA in 7 cottonseed co-products fed to growing pigs. The 7
      cottonseed co-products were: cottonseed meals (solvent extracted) with CP level
      of 46%, 50%, and 55% (46CSM, 50CSM, and 55CSM), cottonseed protein with CP level
      of 50% and 55% (50CSP and 55CSP), fermented cottonseed meal (CSMF), and expelled
      cottonseed meal (CSME). The DE and ME contents of the 7 test ingredients were
      measured using 48 crossbreed barrows (BW: 44.1 +/- 4.2 kg) and 8 diets (including
      a corn-soybean meal basal diet) in a completely randomized design. The AID and
      SID of AA of the 7 test ingredients were determined using 7 crossbreed barrows
      (initial BW: 67.4 +/- 8.5 kg) in a 6 * 8 Youden square design with 6 periods and
      8 diets (including one N-free diet). The DE and ME values of the 7 cottonseed co
      products varied from 12.72 to 15.63 MJ/kg and 12.24 to 14.83 MJ/kg, respectively.
      Among the 7 cottonseed co-products, 55CSP and CSME had the greatest (P < 0.05) ME
      and DE values compared to the other cottonseed co-products. In addition, 55CSP
      had the greatest (P < 0.05) AID and SID of all the AA tested except for Gly and
      Pro. In contrast, 46CSM or 55CSM had the lowest (P < 0.05) AID and SID of all the
      AA tested except for Gly and Pro. The 55CSP also had the greatest (P < 0.05)
      concentrations of standardized ileal digestible CP and all the AA tested except
      for Gly and Pro. In conclusion, the chemical composition, energy, and AA
      digestibility of cottonseed co-products with different processing techniques
      varied widely. Based on the energy and AA digestibility, cottonseed protein with
      CP level of 55% is a better dietary ingredient for growing pigs compared with the
      other cottonseed co-products.

PMID- 29471456
TI  - Effects of resistance training, endurance training and whole-body vibration on
      lean body mass, muscle strength and physical performance in older people: a
      systematic review and network meta-analysis.
AB  - Background: A variety of different types of exercise are promoted to improve
      muscle strength and physical performance in older people. Objective: We aimed to
      determine the relative effects of resistance training, endurance training and
      whole-body vibration on lean body mass, muscle strength and physical performance
      in older people. Design: A systematic review and network meta-analysis. Subjects:
      Adults aged 60 and over. Methods: Evidence from randomised controlled trials of
      resistance training, endurance training and whole-body vibration were combined.
      The effects of exercise interventions on lean body mass, muscle strength and
      physical performance were evaluated by conducting a network meta-analysis to
      compare multiple interventions and usual care. Risk of bias of included studies
      was assessed using the Cochrane Collaboration's tool. A meta-regression was
      performed to assess potential effect modifiers. Results: Data were obtained from
      30 trials involving 1,405 participants (age range: 60-92 years). No significant
      differences were found between the effects of exercise or usual care on lean body
      mass. Resistance training (minimum 6 weeks duration) achieved greater muscle
      strength improvement than did usual care (12.8 kg; 95% confidence interval [CI]:
      8.5-17.0 kg). Resistance training and whole-body vibration were associated with
      greater physical performance improvement compared with usual care (2.6 times
      greater [95% CI: 1.3-3.9] and 2.1 times greater [95% CI: 0.5-3.7], respectively).
      Conclusions: Resistance training is the most effect intervention to improve
      muscle strength and physical performance in older people. Our findings also
      suggest that whole-body vibration is beneficial for physical performance.
      However, none of the three exercise interventions examined had a significant
      effect on lean body mass.

PMID- 29471458
TI  - Pro: The rationale for dietary therapy for patients with advanced chronic kidney
      disease.
AB  - Dietary treatment offers many benefits to patients with advanced chronic kidney
      disease (CKD) who are approaching the need for renal replacement therapy. A large
      number of these benefits are independent of whether diets slow the rate of
      progression of CKD. These diets are low in protein and many minerals, and provide
      adequate energy for the CKD patient. The diets can reduce accumulation of
      potentially toxic metabolic products derived from protein and amino acid
      degradation, maintain a healthier balance of body water, sodium, potassium,
      phosphorus, calcium and other minerals, and prevent or improve protein-energy
      wasting. Such diets may enable patients to safely delay the onset of chronic
      dialysis therapy or kidney transplantation. Dietary therapy may also augment the
      effectiveness of infrequent or incremental dialysis by maintaining healthier
      metabolic and clinical status and may enable some end-stage renal disease
      patients to avoid the need for temporary placement of hemodialysis catheters
      while their arterial venous fistulae or grafts mature. The anxiety that many
      advanced CKD patients commonly experience with regard to starting dialysis may
      incentivize them to accept and adhere to dietary therapy.

PMID- 29471457
TI  - Improving Anatomic Pathology in Sub-Saharan Africa to Support Cancer Care.
AB  - Objectives: Cancer care requires both accurate pathologic diagnosis as well as
      pathologic cancer staging. We evaluated three approaches to training pathologists
      in sub-Saharan Africa to perform pathologic cancer staging of breast, cervix,
      prostate, and colorectal cancers. Methods: One of three training methods was used
      at each workshop: didactic, case-based testing (CBT), or a blended approach. The
      project involved 52 participants from 16 pathology departments in 11 countries in
      East, Central, and Southern Africa. Evaluation of each method included pre- and
      postworkshop knowledge assessments, online pre- and postworkshop surveys of
      practice changes at the individual and institutional levels, and selected site
      visits. Results: While CBT resulted in the highest overall average postassessment
      individual scores, both CBT and blended approaches resulted in 19% increases in
      average scores from pre- to postworkshop assessments. Institutions that
      participated in the blended workshop had increased changes in practice as
      indicated by the institutional survey. Conclusions: Both CBT and a blended
      approach are effective methods for training pathologists in pathologic cancer
      staging. Both are superior to traditional lectures alone.

PMID- 29471459
TI  - Descriptive texture analyses of broiler breast fillets with the wooden breast
      condition stored at 4 degrees C and -20 degrees C.
AB  - The objective of this study was to evaluate the effects of the wooden breast (WB)
      condition on the texture of cooked broiler breast fillets (Pectoralis major)
      after fresh and frozen storage. Texture characteristics of normal (NORM) and
      severe WB fillets were studied by both sensory descriptive analyses and Warner
      Bratzler shear force. Broiler breast fillets were collected over 3 separate trial
      days from a commercial deboning line at 3 h postmortem, classified according to
      the wooden breast condition, and then stored at either 4 degrees C or -20 degrees
      C prior to cooking and texture evaluation. Fillets were cooked to an endpoint
      temperature of 76 degrees C and then evaluated by an 8-member trained sensory
      panel for springiness, cohesiveness, hardness, juiciness, cohesiveness of mass,
      bolus size, wetness of mass, fibrous texture, rate of breakdown, and chewiness.
      The fillets with the WB condition showed higher cook loss than those with NORM
      condition regardless of storage temperature. The mean value of shear force of WB
      fillets was lower than NORM fillets when cooked after 4 degrees C storage.
      Sensory evaluation showed that WB fillets were higher in springiness and
      cohesiveness than NORM fillets and that the sensory attributes springiness,
      hardness and fibrousness were perceived differently between ventral and dorsal
      sections of cooked WB fillets. This work indicates that human perception of
      cooked WB meat has texture irregularities. The cooked breast meat with the WB
      condition is perceived with more springiness and cohesiveness than that with no
      WB condition.

PMID- 29471460
TI  - Coaching primary care clinics for HPV vaccination quality improvement: Comparing
      in-person and webinar implementation.
AB  - State health departments commonly use quality improvement coaching as an
      implementation strategy for improving low human papillomavirus (HPV) vaccination
      coverage, but such coaching can be resource intensive. To explore opportunities
      for improving efficiency, we compared in-person and webinar delivery of coaching
      sessions on implementation outcomes, including reach, acceptability, and delivery
      cost. In 2015, we randomly assigned 148 high-volume primary care clinics in
      Illinois, Michigan, and Washington State to receive either in-person or webinar
      coaching. Coaching sessions lasted about 1 hr and used our Immunization Report
      Card to facilitate assessment and feedback. Clinics served over 213,000 patients
      ages 11-17. We used provider surveys and delivery cost assessment to collect
      implementation data. This report is focused exclusively on the implementation
      aspects of the intervention. More providers attended in-person than webinar
      coaching sessions (mean 9 vs. 5 providers per clinic, respectively, p = .004).
      More providers shared the Immunization Report Card at clinic staff meetings in
      the in-person than webinar arm (49% vs. 20%; p = .029). In both arms, providers'
      belief that their clinics' HPV vaccination coverage was too low increased, as did
      their self-efficacy to help their clinics improve (p < .05). Providers rated
      coaching sessions in the two arms equally highly on acceptability. Delivery cost
      per clinic was $733 for in-person coaching versus $461 for webinar coaching. In
      person and webinar coaching were well received and yielded improvements in
      provider beliefs and self-efficacy regarding HPV vaccine quality improvement. In
      summary, in-person coaching cost more than webinar coaching per clinic reached,
      but reached more providers. Further implementation research is needed to
      understand how and for whom webinar coaching may be appropriate.

PMID- 29471461
TI  - Gendered Pathways to Burnout: Results from the SALVEO Study.
AB  - Aim: Burnout is a pervasive mental health problem in the workforce, with mounting
      evidence suggesting ties with occupational and safety outcomes such as work
      injuries, critical events and musculoskeletal disorders. While environmental
      [work and non-work, work-to-family conflict (WFC)] and individual (personality)
      pathways to burnout are well documented, little is known about how gender comes
      to influence such associative patterns. The aim of the study consisted in
      examining gendered pathways to burnout. Methods: Data were derived from the
      SALVEO study, a cross-sectional study of 2026 workers from 63 workplaces from the
      province of Quebec (Canada). Data were analyzed using multilevel path analysis.
      Results: Direct effects of gendered pathways were evidenced for work (e.g.
      decision latitude) and non-work (e.g. child-related strains) environmental
      pathways, as well as for individual pathways (i.e. internal locus of control).
      Indirect effects of gendered pathways were also evidenced, with women reporting
      higher levels of burnout compared to men due to lower levels of decision latitude
      and of self-esteem, as well as higher levels of WFC. Women also reported lower
      burnout levels through investing more time into domestic tasks, which could
      represent a recovery strategy to highly demanding work. WFC further mediated the
      associations between working hours and burnout, as well as the between irregular
      work schedules and burnout. These result suggest than men distinctively reported
      higher levels of burnout due to the specific nature of their work contract
      negatively impacting on WFC, and incidentally, on their mental health.
      Conclusion: Study results supported our hypotheses positing that gender
      distinctively shapes environmental and individual pathways to burnout. OHS
      prevention efforts striving for better mental health outcomes in the workforce
      could relevantly be informed by a gendered approach to burnout.

PMID- 29471462
TI  - Opening the Door for Immune Oncology Studies in Invasive Lobular Breast Cancer.

PMID- 29471463
TI  - Metapragmatic Explicitation and Social Attribution in Social Communication
      Disorder and Developmental Language Disorder: A Comparative Study.
AB  - Purpose: The purposes of this study are to investigate metapragmatic (MP) ability
      in 6-11-year-old children with social communication disorder (SCD), developmental
      language disorder (DLD), and typical language development and to explore factors
      associated with MP explicitation and social understanding (SU). Method: In this
      cross-sectional study, all participants (N = 82) completed an experimental task,
      the Assessment of Metapragmatics (Collins et al., 2014), in which pragmatic
      errors are identified in filmed interactions. Responses were scored for
      complexity/type of explicitation (MP score) and attribution of social
      characteristics to the films' characters (SU score). Results: Groups with SCD and
      DLD had significantly lower MP scores and less sophisticated explicitation than
      the group with typical language development. After controlling for language and
      age, the group with SCD had significantly lower SU scores than the group with
      DLD. Significant correlations were found between MP scores and age/language
      ability but not with pragmatic impairment. Conclusions: Children with SCD or DLD
      performed poorly on an MP task compared with children who are typically
      developing but do not differ from each other in ability to reflect verbally on
      pragmatic features in interactions. MP ability appears to be closely related to
      structural language ability. The limited ability of children with SCD to
      attribute social/psychological states to interlocutors may indicate additional
      social attribution limitations.

PMID- 29471464
TI  - Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2
      Influenza Vaccine Effectiveness in 2012-2013.
AB  - Background: Influenza vaccination aims to prevent infection by influenza virus
      and reduce associated morbidity and mortality; however, vaccine effectiveness
      (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to
      mismatches between the vaccine and circulating influenza strains and to the
      vaccine's elicitation of protective immunity in only a subset of the population.
      The low H3N2 VE in the 2012-2013 season was attributed to egg-adaptive mutations
      that created antigenic mismatch between the actual vaccine strain (IVR-165) and
      both the intended vaccine strain (A/Victoria/361/2011) and the predominant
      circulating strains (clades 3C.2 and 3C.3). Methods: We investigated the basis of
      low VE in 2012-2013 by determining whether vaccinated and unvaccinated
      individuals were infected by different viral strains and by assessing the
      serologic responses to IVR-165, A/Victoria/361/2011, and 3C.2 and 3C.3 strains in
      an adult cohort before and after vaccination. Results: We found no significant
      genetic differences between the strains that infected vaccinated and unvaccinated
      individuals. Vaccination increased titers to A/Victoria/361/2011 and 3C.2 and
      3C.3 representative strains as much as to IVR-165. These results are consistent
      with the hypothesis that vaccination boosted cross-reactive immune responses
      instead of specific responses against unique vaccine epitopes. Only approximately
      one-third of the cohort achieved a >=4-fold increase in titer. Conclusions: In
      contrast to analyses based on ferret studies, low H3N2 VE in 2012-2013 in adults
      does not appear to be due to egg adaptation of the vaccine strain. Instead, low
      VE might have been caused by low vaccine immunogenicity in a subset of the
      population.

PMID- 29471466
TI  - Changes in Metabolites Present in Lung-Lining Fluid Following Exposure of Humans
      to Ozone.
AB  - Controlled human exposure to the oxidant air pollutant ozone causes decrements in
      lung function and increased inflammation as evidenced by neutrophil influx into
      the lung and increased levels of proinflammatory cytokines in the airways. Here
      we describe a targeted metabolomics evaluation of human bronchoalveolar lavage
      fluid (BALF) following controlled in vivo exposure to ozone to gain greater
      insight into its pulmonary effects. In a 2-arm cross-over study, each healthy
      adult human volunteer was randomly exposed to filtered air (FA) and to 0.3 ppm
      ozone for 2 h while undergoing intermittent exercise with a minimum of 4 weeks
      between exposures. Bronchoscopy was performed and BALF obtained at 1 (n = 9) or
      24 (n = 23) h postexposure. Metabolites were detected using ultrahigh performance
      liquid chromatography-tandem mass spectroscopy. At 1-h postexposure, a total of
      28 metabolites were differentially expressed (DE) (p < .05) following ozone
      exposure compared with FA-exposure. These changes were associated with increased
      glycolysis and antioxidant responses, suggesting rapid increased energy
      utilization as part of the cellular response to oxidative stress. At 24-h
      postexposure, 41 metabolites were DE. Many of the changes were in amino acids and
      linked with enhanced proteolysis. Changes associated with increased lipid
      membrane turnover were also observed. These later-stage changes were consistent
      with ongoing repair of airway tissues. There were 1.37 times as many metabolites
      were differentially expressed at 24 h compared with 1-h postexposure. The changes
      at 1 h reflect responses to oxidative stress while the changes at 24 h indicate a
      broader set of responses consistent with tissue repair. These results illustrate
      the ability of metabolomic analysis to identify mechanistic features of ozone
      toxicity and aspects of the subsequent tissue response.

PMID- 29471465
TI  - Effects of dietary energy level and intake of corn by-product-based diets on
      newly received growing cattle: antibody production, acute phase protein response,
      stress, and immunocompetency of healthy and morbid animals.
AB  - Effects of dietary energy level and intake of corn by-product-based diets on
      antibody production, acute phase protein response, stress, and immunocompetency
      of healthy and morbid newly received growing cattle were evaluated. Four dietary
      treatments were formulated to supply 0.99, 1.10, 1.21, and 1.32 Mcal NEg/ kg DM
      and were offered at 100%, 95%, 90%, and 85% of ad libitum based on 0.99/100
      treatment intake, respectively. Thirty-two pens were utilized with approximately
      12 animals/pen. Four animals from each pen (32/dietary treatment) were randomly
      selected and used to serve as a subset to monitor immune function and acute phase
      proteins following a split-plot design. In addition, two animals were randomly
      and independently selected from each pen (16/dietary treatment) and used to
      measure fecal cortisol metabolite. Additionally, animals removed from the pen one
      (M1), two (M2), or three (M3) times and classified as morbid were bled in
      conjunction with a healthy control (H) removed at the same time and the serum
      analyzed for the same parameters. A quadratic response to time (P < 0.01) was
      detected for haptoglobin concentrations and for antibody titers for bovine viral
      diarrhea type 1 (BVD-I) and infectious bovine rhinotracheitis (IBR; P < 0.01).
      Haptoglobin was lowest on arrival, highest on day 14, and similar to baseline
      levels by day 27. Titer levels for BVD-I and IBR were lowest on arrival, higher
      on day 14, and significantly higher on day 27. Titers for bovine viral diarrhea
      type 2 (BVD-II) responded linearly (P < 0.05) with lower levels on arrival and
      highest levels on day 27. Haptoglobin was elevated in morbid animals compared to
      healthy pen mates (P < 0.05). Titer levels for BVD-I and IBR were also higher in
      healthy animals compared to animals pulled for morbidity (P < 0.01). Fecal
      cortisol was higher on arrival than on day 14 (P < 0.05). Dietary treatment had
      no effect on any of the parameters investigated. In summary, high-energy
      receiving diets based on fermentable fiber from by-products can be fed to newly
      received growing cattle without negative effects on antibody production toward
      vaccines, inflammation, or overall stress. In addition, haptoglobin
      concentrations and titer levels for BVD-I and IBR viruses are higher in healthy
      animals compared to sick animals.

PMID- 29471467
TI  - Myeloperoxidase influences the complement regulatory activity of complement
      factor H.
AB  - Objective: The interaction between neutrophils and activation of alternative
      complement pathway plays a critical role in the pathogenesis of ANCA-associated
      vasculitis (AAV). MPO, which can be released from ANCA-stimulated neutrophils,
      was recently demonstrated to be capable of activating the alternative complement
      pathway. Here we aimed to investigate the interaction between MPO and factor H
      (FH), a key regulator of the alternative pathway, and its effect on the
      functional activities of FH. Methods: Detection of FH and MPO on neutrophil
      extracellular traps (NETs) induced by serum from AAV patients and in kidney
      biopsies of AAV patients was performed by immunostaining. In vitro binding
      between MPO and FH was examined by ELISA and surface plasmon resonance. The
      influence of MPO on the complement regulatory activity of FH was further
      assessed. Results: FH deposited and co-localized with MPO in NETs. In kidney
      biopsies from AAV patients, MPO was closely adjacent to FH in glomerular
      capillaries. We demonstrated that MPO binds to FH with an apparent nanomolar
      affinity and identified short consensus repeats 1-4 of FH as the major binding
      sites. In terms of functional analysis, MPO inhibited the interaction between FH
      and C3b and the decay-accelerating activity of FH. The fluid phase and surface
      cofactor activities of FH upon C3b inactivation were inhibited by MPO.
      Conclusion: Our findings indicate that MPO binds to FH and influences the
      complement regulatory activity of FH. MPO-FH interaction may participate in the
      pathogenesis of AAV by contributing to activation of the alternative complement
      pathway.

PMID- 29471468
TI  - Working conditions and stress in the English education system.
AB  - Background: The UK education sector has among the highest level of stress
      sickness absence of all occupations. However, investigations of psychosocial
      working conditions which contribute to stress, including behaviour of students
      and parents, has not been conducted. Aims: To investigate the psychosocial
      working conditions and prevalence of negative parental and student behaviour in a
      large sample of school teachers and college lecturers based in England. In
      addition, to assess the influence of working conditions, student behaviour and
      parental behaviour on perceived stress. Methods: A cross-sectional survey of
      teachers in England. Respondents completed the Management Standards Indicator
      Tool (MSIT), Perceived Stress Scale (PSS-4), Student Behaviour Scale and a two
      item measure of parental behaviour. Differences in these measures across
      different teaching roles were assessed using analysis of variance. Regression
      analyses were used to evaluate the association of MSIT, student and parental
      behaviour on PSS outcomes. Results: Compared to UK benchmark scoring,
      psychosocial working conditions were at a poor level, with primary teachers in
      particular exposed to negative parental behaviours, and secondary teachers to
      poor student behaviour. Demands were consistently associated with perceived
      stress outcomes across job roles, although management support and relationships
      with peers also played a part. Conclusions: Demands faced by teachers in England
      played an important part in the experience of stress. Interventions to reduce
      these demands, and the high frequencies of negative pupil and parental
      behaviours, should be considered.

PMID- 29471470
TI  - A Registry for Patients With Asplenia/Hyposplenism Reduces the Risk of Infections
      With Encapsulated Organisms.
AB  - Background: Overwhelming post-splenectomy infection (OPSI) is a serious
      complication of asplenia. Clinical guidelines recommend numerous measures to
      reduce the risk of OPSI, but awareness and adherence to preventative measures are
      generally poor. We aimed to determine whether a registry for asplenic/hyposplenic
      patients was associated with a reduction in the incidence of infection with
      encapsulated bacteria. Methods: We performed a retrospective cohort study of
      asplenic/hyposplenic patients in the state of Victoria, Australia, who registered
      with Spleen Australia from 2003 through 2014. Spleen Australia provides
      education, clinical guidance, and annual vaccination reminders to registrants and
      their healthcare providers. We compared the incidence of infection with
      Streptococcus pneumoniae, Haemophilus influenzae type B (Hib), and Neisseria
      meningitidis before and after registration. Registry data were linked with
      Victorian notifiable disease data on invasive pneumococcal disease (IPD),
      invasive meningococcal disease (IMD), and Hib between 2000 and 2014. Results:
      Twenty-seven cases of IPD and 1 of IMD occurred among 3221 registrants. No cases
      of Hib were reported. The rate of IPD/IMD was 150 per 100000 patient-years prior
      to registration and 36 per 100000 patient-years after registration; registration
      was associated with a 69% reduction in the risk of infection (incidence rate
      ratio, 0.31; 95% confidence interval, 0.12 to 0.83; P = .019). Based on the
      absolute reduction in incidence, we estimate that Spleen Australia prevents 5-6
      invasive infections with encapsulated organisms annually among registrants.
      Conclusions: Systematic, long-term approaches to post-splenectomy care can
      significantly reduce the risk of infection with encapsulated organisms among
      individuals with asplenia/hyposplenism.

PMID- 29471469
TI  - Effect of lemon leaves on energy and C-N balances, methane emission, and milk
      performance in Murciano-Granadina dairy goats.
AB  - The objective of this experiment was to find out the effect of lemon leaves on
      energy and C-N balances, methane emission, and milk performance in dairy goats.
      Lemon leaves were used to replace alfalfa as forage in a diet for Murciano
      Granadina goats. Ten Murciano-Granadina dairy goats (44.1 +/- 4.47 kg of BW) in
      late lactation (185 +/- 7.2 d) were selected in a crossover design experiment,
      where each goat received 2 treatments in 2 periods. One group was fed a mixed
      ration with 450 g of pelleted alfalfa per kilogram of DM (ALF diet) and, the
      other group replaced alfalfa with 450 g of pelleted lemon leaves per kilogram DM
      (LEM diet). The concentrate was pelleted, being the same for the two groups
      (forage to concentrate ratio was 45/55). The goats were allocated to individual
      metabolism cages. After 14 d of adaptation, feed intake, total fecal and urine
      output, and milk yield were recorded daily over a 5-d period. Then, gas exchange
      measurements were recorded individually by an open-circuit indirect calorimetry
      system using a head box. Higher dietary lipids in LEM diet reduced DMI (200 g/d)
      and energy intake (251 kJ/kg of BW0.75), although no differences between
      treatments were observed for ME intake (998 kJ/kg of BW0.75, on average) and
      oxidation of nutrients (64% and 25% for carbohydrates and fat oxidation,
      respectively, on heat production from oxidation basis). Greater (P < 0.05) milk
      fat values for C18:2n6t and CLA 9c11t + 9t11c were found in LEM compared with ALF
      diet. Goats fed LEM diet produced significantly fewer CH4 emissions than ALF diet
      (18%). Likewise, the use of lemon leaves as forage reduced the amount of CH4 in
      2.7 g/kg of milk. Results suggest that lemon leaves are effective in reducing CH4
      emission without detrimental effect on milk yield.

PMID- 29471471
TI  - Cohort Profile: Maternal mental health and child development in situations of
      past violent conflict and ongoing adversity: the DILI birth cohort study.

PMID- 29471472
TI  - Commentary: Beyond child survival: public policy priorities for avoiding
      premature adult mortality.

PMID- 29471474
TI  - The Crus exhibits stronger functional connectivity with executive network nodes
      than with the default mode network.

PMID- 29471473
TI  - Bidirectional GPR119 Agonism Requires Peptide YY and Glucose for Activity in
      Mouse and Human Colon Mucosa.
AB  - The lipid sensor G protein-coupled receptor 119 (GPR119) is highly expressed by
      enteroendocrine L-cells and pancreatic beta-cells that release the hormones,
      peptide YY (PYY) and glucagonlike peptide 1, and insulin, respectively.
      Endogenous oleoylethanolamide (OEA) and the dietary metabolite, 2
      monoacylglycerol (2-OG), can each activate GPR119. Here, we compared mucosal
      responses with selective, synthetic GPR119 agonists (AR440006 and AR231453) and
      the lipids, OEA, 2-OG, and N-oleoyldopamine (OLDA), monitoring epithelial ion
      transport as a readout for L-cell activity in native mouse and human
      gastrointestinal (GI) mucosae. We also assessed GPR119 modulation of colonic
      motility in wild-type (WT), GPR119-deficient (GPR119-/-), and PYY-deficient (PYY
      /-) mice. The water-soluble GPR119 agonist, AR440006 (that cannot traverse
      epithelial tight junctions), elicited responses, when added apically or
      basolaterally in mouse and human colonic mucosae. In both species, GPR119
      responses were PYY, Y1 receptor mediated, and glucose dependent. AR440006
      efficacy matched the GI distribution of L-cells in WT tissues but was absent from
      GPR119-/- tissue. OEA and 2-OG responses were significantly reduced in the GPR119
      /- colon, but OLDA responses were unchanged. Alternative L-cell activation via
      free fatty acid receptors 1, 3, and 4 and the G protein-coupled bile acid
      receptor TGR5 or by the melanocortin 4 receptor, was unchanged in GPR119-/-
      tissues. The GPR119 agonist slowed transit in WT but not the PYY-/- colon in
      vitro. AR440006 (intraperitoneally) slowed WT colonic and upper-GI transit
      significantly in vivo. These data indicate that luminal or blood-borne GPR119
      agonism can stimulate L-cell PYY release with paracrine consequences and slower
      motility. We suggest that this glucose-dependent L-cell response to a gut
      restricted GPR119 stimulus has potential therapeutic advantage in modulating
      insulinotropic signaling with reduced risk of hypoglycemia.

PMID- 29471476
TI  - 10th European Public Health Conference: Sustaining resilient and healthy
      communities, Stockholm, Sweden, 1-4 November 2017.

PMID- 29471475
TI  - Assessing Viral Transfer During Doffing of Ebola-Level Personal Protective
      Equipment in a Biocontainment Unit.
AB  - Background: Personal protective equipment (PPE) protects healthcare workers
      (HCWs) caring for patients with Ebola virus disease (EVD), and PPE doffing is a
      critical point for preventing viral self-contamination. We assessed contamination
      of skin, gloves, and scrubs after doffing Ebola-level PPE contaminated with
      surrogate viruses: bacteriophages MS2 and Phi6. Methods: In a medical
      biocontainment unit, HCWs (n = 10) experienced in EVD care donned and doffed PPE
      following unit protocols that incorporate trained observer guidance and alcohol
      based hand rub (ABHR). A mixture of Phi6 (enveloped), MS2 (nonenveloped), and
      fluorescent marker was applied to 4 PPE sites, approximating body fluid viral
      load (Phi6, 105; MS2, 106). They performed a patient care task, then doffed.
      Inner gloves, face, hands, and scrubs were sampled for virus, as were
      environmental sites with visible fluorescent marker. Results: Among 10 HCWs there
      was no Phi6 transfer to inner gloves, hands, or face; 1 participant had Phi6 on
      scrubs at low levels (1.4 * 102). MS2 transfer (range, 101-106) was observed to
      scrubs (n = 2), hands (n = 1), and inner gloves (n = 7), where it was highest.
      Most (n = 8) had only 1 positive site. Environmental samples with visible
      fluorescent marker (n = 21) were negative. Conclusions: Among experienced HCWs,
      structured, observed doffing using ABHR protected against hand contamination with
      enveloped virus. Nonenveloped virus was infrequent on hands and scrubs but common
      on inner gloves, suggesting that inner gloves, but not necessarily ABHR, protect
      against hand contamination. Optimizing doffing protocols to protect against all
      types of viruses may require reinforcing careful handling of scrubs and good
      glove/hand hygiene with effective agents.

PMID- 29471477
TI  - Feasibility of smartphone application and social media intervention on breast
      cancer survivors' health outcomes.
AB  - Breast cancer survivors are at risk for poor health, with physical activity a
      possible treatment. Little research has examined how technology might promote
      breast cancer survivor physical activity or health. The aim of this study is to
      investigate the feasibility of employing a commercially available mobile health
      application- and social media-based health education intervention to improve
      breast cancer survivor physical activity or health.Ten breast cancer survivors (X
      age = 45.80 +/- 10.23 years; X weight = 79.51 +/- 20.85 kg) participated in this
      10-week single-group pilot study from 2015 to 2016. Participants downloaded the
      MapMyFitness application, documented all physical activity with MapMyFitness, and
      were enrolled in a Social Cognitive Theory-based, Facebook-delivered health
      education intervention. Objectively measured physical activity, weight or body
      composition, cardiovascular fitness, psychosocial constructs, and quality of life
      indices were measured at baseline and 10 weeks. Intervention use and
      acceptability was evaluated during and following the intervention. Descriptive
      statistics were calculated for all study outcomes, with qualitative analyses
      performed regarding use and acceptability. At postintervention, average daily
      moderate-to-vigorous physical activity and steps increased by 2.6 min and 1,657,
      respectively, with notable decreases in weight (2.4 kg) and body fat percentage
      (2.3%). Physical activity-related social support and ability to engage in social
      roles or activity demonstrated the greatest improvements among all psychosocial
      and quality of life indices, respectively. Participants enjoyed the feedback and
      tracking features of MapMyFitness, with most finding the Facebook component
      helpful. All participants recommended the intervention for future use.Physical
      activity interventions combining commercially available mobile health
      applications and theoretically based social media-delivered health interventions
      may promote certain physiological, psychosocial, and quality of life outcomes
      among breast cancer survivors. Larger samples and randomized studies are
      warranted.

PMID- 29471478
TI  - Internet-Delivered Cognitive-Behavioral Therapy for Insomnia in Breast Cancer
      Survivors: A Randomized Controlled Trial.
AB  - Background: Insomnia is two to three times more prevalent in cancer survivors
      than in the general population, where it is estimated to be 10% to 20%. Cognitive
      behavioral therapy for insomnia (CBT-I) is the recommended treatment for chronic
      insomnia, but meeting survivor needs remains a challenge. Internet-delivered CBT
      I (iCBT-I) has been shown efficacious in otherwise healthy adults. We tested the
      efficacy of iCBT-I in breast cancer survivors with clinically significant sleep
      disturbance. Methods: Women from a national sample of Danish breast cancer
      survivors who experienced clinically significant sleep disturbance were randomly
      allocated to iCBT-I or waitlist control (55:45). The fully automated iCBT-I
      program consisted of six cores. Online measures of insomnia severity, sleep
      quality, and fatigue were collected at baseline, postintervention (nine weeks),
      and follow-up (15 weeks). Online sleep diaries were completed over two-week
      periods pre- and postintervention. Intention-to-treat analyses (time * group
      interactions) were conducted with mixed linear models and corrected for multiple
      outcomes. All statistical tests were two-sided. Results: A total of 255 women
      were randomly allocated to iCBT-I (n = 133) or waitlist control (n = 122).
      Statistically significant (P <= .02) time * group interactions were found for all
      sleep-related outcomes from pre- to postintervention. Effect sizes (Cohen's d)
      ranged from 0.33 (95% confidence interval [CI] = 0.06 to 0.61) for wake after
      sleep onset to 1.17 (95% CI = 0.87 to 1.47) for insomnia severity. Improvements
      were maintained for outcomes measured at follow-up (d = 0.66-1.10). Conclusions:
      iCBT-I appears to be effective in breast cancer survivors, with additional
      benefit in terms of reduced fatigue. This low-cost treatment could be
      incorporated in cancer rehabilitation programs.

PMID- 29471479
TI  - Seasonal Effects and the Impact of In-Hive Pesticide Treatments on Parasite,
      Pathogens, and Health of Honey Bees.
AB  - Honey bee, Apis mellifera (L.; Hymenoptera: Apidae), populations are in decline
      and their losses pose a serious threat for crop pollination and food production.
      The specific causes of these losses are believed to be multifactorial.
      Pesticides, parasites and pathogens, and nutritional deficiencies have been
      implicated in the losses due to their ability to exert energetic stress on bees.
      While our understanding of the role of these factors in honey bee colony losses
      has improved, there is still a lack of knowledge of how they impact the immune
      system of the honey bee. In this study, honey bee colonies were exposed to
      Fumagilin-B, Apistan (tau-fluvalinate), and chlorothalonil at field realistic
      levels. No significant effects of the antibiotic and two pesticides were observed
      on the levels of varroa mite, Nosema ceranae (Fries; Microsporidia: Nosematidae),
      black queen cell virus, deformed wing virus, or immunity as measured by
      phenoloxidase and glucose oxidase activity. Any effects on the parasites,
      pathogens, and immunity we observed appear to be due mainly to seasonal changes
      within the honey bee colonies. The results suggest that Fumagilin-B, Apistan, and
      chlorothalonil do not significantly impact the health of honey bee colonies,
      based on the factors analyzed and the concentration of chemicals tested.

PMID- 29471480
TI  - Family Medicine Clinic: a case study of a hospital-family medicine practice
      redesign to improve chronic disease care in the community in Singapore.
AB  - Background: Singapore's health care system is strained by the health care needs
      of a rapidly aging population. The unprecedented collaboration between a public
      hospital and a private family practice to set up the Family Medicine Clinic (FMC)
      to co-manage patients with chronic disease is an example of efforts to shift care
      to the community. Objective: To explore patients' initial experience of shared
      chronic disease care in a private family practice setting. Methods: In this
      exploratory case study, we surveyed 330 patients with stable chronic diseases and
      interviewed 10 complex care patients and their caregivers. Results: Most patients
      were willing to transfer their care from the hospital to a FMC and satisfied with
      the care received. Patients reported enhanced access at FMC and appreciated the
      improvement in care continuity and care coordination across settings. Patients
      with complex care needs felt engaged with their case manager even though they did
      not understand case management. Despite the favourable assessment of FMC,
      patients sought care from other health care providers and a third of patients
      would leave if the subsidy for their care at FMC was removed. Families and
      caregivers felt that their needs could be better addressed and that FMC could
      play a role. Conclusions: To ensure that patients' initial positive experience
      translates to a long-term relationship with FMC, providers should move beyond
      providing improved access to care. It is necessary to help patients understand
      the comparative advantage of community-based care and its contribution to long
      term health outcomes. Providers should also elicit patients' desires and
      expectations when designing future models of care. At a policy level, higher cost
      of private primary care should be addressed.

PMID- 29471482
TI  - Discovery of Haemaphysalis longicornis (Ixodida: Ixodidae) Parasitizing a Sheep
      in New Jersey, United States.
AB  - We report the discovery of large numbers of Haemaphysalis longicornis Neumann
      (Ixodida: Ixodidae) infesting a sheep in Hunterdon County, New Jersey, United
      States. All life stages were found on the sheep, which had no history of travel
      outside the country. H. longicornis is native to East Asia, and there are
      invasive populations in Australia, New Zealand and several Pacific islands, where
      this tick is a major livestock pest. It is currently unknown whether the New
      Jersey collections represent a limited or established population, but because
      this species could present a significant threat to human and animal health in the
      United States, vigilance is encouraged.

PMID- 29471481
TI  - Bacterial-fungal interactions: ecology, mechanisms and challenges.
AB  - Fungi and bacteria are found living together in a wide variety of environments.
      Their interactions are significant drivers of many ecosystem functions and are
      important for the health of plants and animals. A large number of fungal and
      bacterial families engage in complex interactions that lead to critical
      behavioural shifts of the microorganisms ranging from mutualism to antagonism.
      The importance of bacterial-fungal interactions (BFI) in environmental science,
      medicine and biotechnology has led to the emergence of a dynamic and
      multidisciplinary research field that combines highly diverse approaches
      including molecular biology, genomics, geochemistry, chemical and microbial
      ecology, biophysics and ecological modelling. In this review, we discuss recent
      advances that underscore the roles of BFI across relevant habitats and
      ecosystems. A particular focus is placed on the understanding of BFI within
      complex microbial communities and in regard of the metaorganism concept. We also
      discuss recent discoveries that clarify the (molecular) mechanisms involved in
      bacterial-fungal relationships, and the contribution of new technologies to
      decipher generic principles of BFI in terms of physical associations and
      molecular dialogues. Finally, we discuss future directions for research in order
      to stimulate synergy within the BFI research area and to resolve outstanding
      questions.

PMID- 29471483
TI  - Transfer accuracy of two indirect bonding techniques-an in vitro study with 3D
      scanned models.
AB  - Background and objectives: Indirect bonding (IDB) proved to be an effective
      method for appropriate bracket positioning in patients. Different methods and
      materials are available for fabricating transfer trays. This in vitro study was
      designed to measure and compare the transfer accuracy of two common IDB methods.
      Materials and methods: Sixty stone models were fabricated and separated in two
      groups of 30 models each (15 working models, 15 patient models). After placing
      brackets on the working models, 30 IDB trays were made: 15 silicone (method I)
      and 15 double-vacuum forms (method II). With these trays, the brackets were
      transferred to the patient models. The bracket positions were scanned before and
      after the IDB procedure with an intraoral scanner. The linear and angular
      discrepancies were then determined digitally by measuring six different
      dimensions: occluso-cervical, mesio-distal, bucco-lingual, tip, rotation, and
      torque. Results: The silicone trays showed fewer transfer discrepancies, on
      average, in all measured dimensions. There were significant differences between
      the methods in the occluso-cervical (P < 0.001), mesio-distal (P = 0.001), and
      torque (P = 0.044) dimensions. With both methods, 100 per cent of the horizontal
      and transversal measurements of both methods were within the clinically
      acceptable range of 0.25 mm. With method I, 98.5 per cent of the vertical and
      95.9 per cent of the angular measurements were within the range of 0.25 mm and 1
      degrees , respectively. With method II, 94 per cent of the vertical and 84.8 per
      cent of the angular measurements were within the clinically acceptable range.
      Conclusions: Although both transfer methods showed a high precision, silicone
      trays scored better in terms of accuracy than double-vacuum forms.

PMID- 29471484
TI  - A study of the knowledge, attitudes and practices of Tibetan yak herders with
      respect to brucellosis.
AB  - Background: Little information is available regarding the knowledge, attitudes
      and practices (KAP) of the owners of yaks in Tibet with respect to brucellosis.
      Methods: This manuscript reports on the results of a cross-sectional survey using
      a structured questionnaire investigating the KAP of 317 yak herders from 34
      villages in the three main yak-rearing counties of Maizhokunggar, Damxung and
      Yadong from April to August 2015. Results: Although 60.6% of the respondents had
      heard of brucellosis, there was an overall low level of knowledge about the
      disease. Herders did, however, adopt management/husbandry practices which would
      reduce transmission of the disease to humans and other animals. Multivariable
      logistic modelling showed that a better knowledge was predicted by age,
      production system adopted, education level and number of people in a household.
      Differences in attitudes and practices were predicted by education level,
      production system and household size. Conclusions: In order to increase the
      awareness of herders on brucellosis and to reduce the risk of infection in both
      humans and other animals, public health education campaigns should be developed
      and offered to livestock owners in Tibet.

PMID- 29471485
TI  - Trabecular bone score as an assessment tool to identify the risk of osteoporosis
      in axial spondyloarthritis: a case-control study.
AB  - Objectives: To compare the trabecular bone score (TBS) between patients with
      axial spondyloarthritis (axSpA) and matched normal controls and identify risk
      factors associated with a low TBS. Methods: TBS and BMD were assessed in the two
      groups (axSpA and control) using DXA. Osteoporosis risk factors and inflammatory
      markers were also assessed. Disease activity and radiographic progression in the
      sacroiliac joint and spine were evaluated in the axSpA group. Multivariate linear
      regression analysis was performed to identify risk factors associated with TBS.
      Results: In the axSpA group, 248 subjects were enrolled; an equal number of age-
      and sex-matched subjects comprised the control group. The mean TBS was 1.43
      (0.08) and 1.38 (0.12) in the control and axSpA groups, respectively (P < 0.001);
      BMD at the lumbar spine did not differ between the two groups. The TBS was
      negatively correlated with ESR and CRP levels in the axSpA group only (P < 0.001
      and P = 0.007, respectively). Syndesmophytes in the axSpA group was associated
      with lower TBS (P < 0.001) but higher lumbar BMD (P = 0.021) vs controls. In the
      multivariate analyses, ESR, CRP and spinal radiographic progression were
      significantly associated with TBS. Conclusion: TBS assessments revealed poor bone
      quality in patients with axSpA compared with the matched controls. In axSpA,
      systemic inflammatory markers were negatively correlated with TBS and spinal
      radiographic progression and inflammatory markers were independently correlated
      with low TBS. TBS may, therefore, be a useful clinical tool to identify the risk
      of osteoporosis in patients with axSpA.

PMID- 29471486
TI  - Selection of hyperproduction of AmpC and SME-1 in a carbapenem-resistant Serratia
      marcescens isolate during antibiotic therapy.
AB  - Objectives: Antibiotic selective pressure may result in changes to antimicrobial
      susceptibility throughout the course of infection, especially for organisms that
      harbour chromosomally encoded AmpC beta-lactamases, notably Enterobacter spp., in
      which hyperexpression of ampC may be induced following treatment with
      cephalosporins. In this study, we document a case of bacteraemia caused by a
      blaSME-1-harbouring Serratia marcescens that subsequently developed resistance to
      expanded-spectrum cephalosporins, piperacillin/tazobactam and fluoroquinolones,
      over the course of several months of treatment with piperacillin/tazobactam and
      ciprofloxacin. Methods: Susceptibility testing and WGS were performed on three S.
      marcescens isolates from the patient. beta-Lactamase activity in the presence or
      absence of induction by imipenem was measured by nitrocefin hydrolysis assays.
      Expression of ampC and blaSME-1 under the same conditions was determined by real
      time PCR. Results: WGS demonstrated accumulation of missense and nonsense
      mutations in ampD associated with stable derepression of AmpC. Gene expression
      and beta-lactamase activity of both AmpC and SME-1 were inducible in the initial
      susceptible isolate, but were constitutively high in the resistant isolate, in
      which total beta-lactamase activity was increased by 128-fold. Conclusions:
      Although development of such in vitro resistance due to selective pressure
      imposed by antibiotics is reportedly low in S. marcescens, our findings highlight
      the need to evaluate isolates on a regular basis during long-term antibiotic
      therapy.

PMID- 29471487
TI  - The Lesser Antillean Iguana (Iguana delicatissima) on St. Eustatius: Genetically
      Depauperate and Threatened by Ongoing Hybridization.
AB  - The Lesser Antillean Iguana (Iguana delicatissima) is an endangered species
      threatened by habitat loss and hybridization with non-native Green Iguanas
      (Iguana iguana). Iguana delicatissima has been extirpated on several islands, and
      the Green Iguana has invaded most islands with extant populations. Information is
      essential to protect this species from extinction. We collected data on 293
      iguanas including 17 juveniles from St. Eustasius, one of the few remaining I.
      delicatissima strongholds. Genetic data were leveraged to test for hybridization
      presence with the Green Iguana using both mitochondrial and nuclear genes,
      including 16 microsatellite loci. The microsatellites were also analyzed to
      estimate genetic diversity, population structure, and effective population size.
      Using molecular and morphological data, we identified 286 I. delicatissima
      individuals captured during our first fieldwork effort, and 7 non-native iguanas
      captured during a second effort, showing hybridization occurs within this
      population. Comparing homologous microsatellites used in studies on Dominica and
      Chancel, the I. delicatissima population on St. Eustatius has extremely low
      genetic diversity (HO = 0.051; HE = 0.057), suggesting this population is
      genetically depauperate. Furthermore, there is significant evidence for
      inbreeding (FIS = 0.12) and weak spatial genetic structure (FST = 0.021, P =
      0.002) within this population. Besides immediate threats including hybridization,
      this population's low genetic diversity, presence of physiological abnormalities
      and low recruitment could indicate presence of inbreeding depression that
      threatens its long-term survival. We conclude there is a continued region-wide
      threat to I. delicatissima and highlight the need for immediate conservation
      action to stop the continuing spread of Green Iguanas and to eliminate
      hybridization from St. Eustatius.

PMID- 29471488
TI  - Morphological responses of plant roots to mechanical stress.
AB  - Background: Roots are continuously exposed to mechanical pressure and this often
      results in their morphological modification. Most obvious are changes in the
      overall form of the root system as well as in the shapes of particular roots.
      These changes are often accompanied by modifications of the cell pattern and cell
      morphology. Scope: This review focuses on the morphological responses of roots to
      mechanical stress. Results of early and recent experiments in which roots have
      been exposed to mechanical pressure are assembled, analysed and discussed.
      Research applying different experimental sets, obstacles, media of various
      compactness and structure are reviewed. An effect of the combination of
      mechanical stresses with other abiotic stresses on roots, and results of
      estimating the force exerted by the roots are briefly discussed. Possible
      consequences of the cell pattern rearrangements are considered. Conclusions:
      Several modifications in root morphology are commonly reported: (1) decreased
      root size, (2) radial swelling accompanied by increased radial dimension of the
      cortex cell layers and (3) enhanced cap cell sloughing. Nevertheless, because of
      differences between species and individual plants, a universal scenario for root
      morphological changes resulting from externally applied pressures is not
      possible. Thus, knowledge of the root response to mechanical impedance remains
      incomplete. Studies on the mechanical properties of the root as well as on
      possible modifications in cell wall structure and composition as the elements
      responsible for the mechanical properties of the plant tissue are required to
      understand the response of root tissue as a biomaterial.

PMID- 29471489
TI  - The H-subunit of the restriction endonuclease CglI contains a prototype DEAD-Z1
      helicase-like motor.
AB  - CglI is a restriction endonuclease from Corynebacterium glutamicum that forms a
      complex between: two R-subunits that have site specific-recognition and nuclease
      domains; and two H-subunits, with Superfamily 2 helicase-like DEAD domains, and
      uncharacterized Z1 and C-terminal domains. ATP hydrolysis by the H-subunits
      catalyses dsDNA translocation that is necessary for long-range movement along DNA
      that activates nuclease activity. Here, we provide biochemical and molecular
      modelling evidence that shows that Z1 has a fold distantly-related to RecA, and
      that the DEAD-Z1 domains together form an ATP binding interface and are the
      prototype of a previously undescribed monomeric helicase-like motor. The DEAD-Z1
      motor has unusual Walker A and Motif VI sequences those nonetheless have their
      expected functions. Additionally, it contains DEAD-Z1-specific features: an H/H
      motif and a loop (aa 163-aa 172), that both play a role in the coupling of ATP
      hydrolysis to DNA cleavage. We also solved the crystal structure of the C
      terminal domain which has a unique fold, and demonstrate that the Z1-C domains
      are the principal DNA binding interface of the H-subunit. Finally, we use small
      angle X-ray scattering to provide a model for how the H-subunit domains are
      arranged in a dimeric complex.

PMID- 29471490
TI  - Pharmacologic assessment of bovine ruminal and mesenteric vascular serotonin
      receptor populations.
AB  - Prior work using a contractility bioassay determined that the serotonin (5-HT)
      receptor subtype 5-HT2A is present in bovine lateral saphenous veins and plays a
      role in ergot alkaloid (EA)-induced vascular contraction in steers grazing
      endophyte-infected (Epichloe coenophiala) tall fescue (Lolium arundinaceum).
      Ergot alkaloids have also been shown to be vasoactive in bovine gut vasculature.
      To determine what 5-HT receptors are involved in vasoconstriction of gut
      vasculature, contractility of ruminal and mesenteric arteries and veins collected
      from cattle was evaluated in the presence of agonists selective for 5-HT1B (CP
      93129), 5-HT1D (L-694, 247), 5-HT2A (TCB-2), 5-HT2B (BW 723C86), 5-HT4 (BIMU-8),
      and 5-HT7 (LP 44) receptors. Segments of ruminal and mesenteric veins and
      arteries were collected and suspended in a multimyograph containing continuously
      oxygenated Krebs-Henseleit buffer. Blood vessels were exposed to increasing
      concentrations of 5-HT agonists every 15 min and contractile response data were
      normalized as a percentage of the maximum contractile response induced by 120 mM
      KCl. Analysis of variance was evaluated using mixed models procedure of SAS for
      effects of agonist concentration for each vessel type. Receptor agonists for 5
      HT2B, 5-HT1D, and 5-HT7 did not induce a contractile response for ruminal or
      mesenteric vasculature (P > 0.05). However, when exposed to agonists for 5-HT2B
      or 5-HT1D, mesenteric veins relaxed below zero (P < 0.05). Exposure of all 4
      blood vessel types to 5-HT2A agonist induced contractile responses (P < 0.05).
      The findings of this study indicate that 5-HT1D and 5-HT2B are present in
      mesenteric veins and may play a role in vasorelaxation. Further, 5-HT2A is
      present in ruminal and mesenteric vasculature, plays a role in vasoconstriction
      of these vessels, and could be influenced by EA exposure as has been demonstrated
      in peripheral blood vessels.

PMID- 29471491
TI  - Farming characteristics and self-reported health outcomes of Irish farmers.
AB  - Background: Irish farmers represent a 'high-risk' group for non-communicable
      diseases, which, arguably, pose a greater occupational health challenge for
      farmers. To date, there has been little exploration of the farming
      characteristics associated with farmers' poor health outcomes. Aims: To examine
      the relationship between farming and male farmers' self-reported health outcomes
      and to compare the study findings to national health studies to explore which
      factors specifically are associated with Irish farmers' poorer health outcomes
      relative to the general population. Methods: This cross-sectional survey research
      used self-reported quantitative data on the health outcomes and health behaviours
      of male farmers from the South-East of Ireland. Data were entered into SPSS and
      descriptive and binary regression techniques were used for data analysis.
      Results: There were 314 participants (99% response rate). Age, full-time farming
      and dairy farming significantly impacted self-reported health outcomes and health
      behaviours. There was a high prevalence of self-reported arthritis compared with
      the national average of Irish males. 'Younger' farmers (<45 years) were more
      likely to engage in harmful health behaviours such as smoking and 'binge
      drinking' one or more times per week. Conclusions: This study identified self
      reported patterns of risky lifestyle behaviours among particular subgroups of
      Irish farmers for whom targeted health interventions are warranted. Interventions
      are particularly important for younger farmers who may see themselves as
      invincible and impregnable to ill-health.

PMID- 29471492
TI  - Corrigendum: Towards recommendations for metadata and data handling in plant
      phenotyping.

PMID- 29471493
TI  - The effect of pregnancy on endometriosis-facts or fiction?
AB  - BACKGROUND: It is not uncommon for women with endometriosis to be advised that
      becoming pregnant might be a useful strategy to manage their symptoms and reduce
      disease progression. Consequently, many women diagnosed with endometriosis and
      motivated to become pregnant, may also have expectations regarding improvement of
      symptoms and the disease. However, study results on the effect of pregnancy on
      endometriosis are controversial and pregnancy in women with endometriosis is not
      always associated with improved symptoms. Moreover, there is increasing evidence
      that endometriosis may interfere with a successful pregnancy outcome. OBJECTIVE
      AND RATIONALE: The objective was to evaluate the evidence on whether pregnancy
      and lactation has a beneficiary effect on growth characteristics and symptoms of
      endometriosis diagnosed prior to pregnancy. SEARCH METHODS: A search for articles
      containing keywords related to pregnancy and endometriosis was performed via
      PubMed. Manuscripts dealing with a potential effect of pregnancy on endometriosis
      were systematically reviewed. We included English, French and German language
      publications on human studies from 1966 to May 2017. Bibliographies of these
      manuscripts were searched for further relevant literature. OUTCOMES: Five small
      observational studies were identified concerning the longitudinal development of
      endometriotic lesions during and after pregnancy, four of medium and one of low
      quality. Eleven publications reported measurements of endometriomas during
      pregnancy and the postpartum period (the five studies just mentioned and six case
      reports). Another 22 case reports/small case series (maximum of five cases), six
      studies on histology of endometriotic lesions in pregnancy, plus eight studies on
      the role of pregnancy in initial development and recurrence of endometriosis were
      included. Few studies of very limited quality are available to evaluate the
      effect of pregnancy and the postnatal period on the development of endometriosis.
      The development of endometriosis is variable and there is no evidence that
      pregnancy can be expected to generally reduce the size and number of
      endometriotic lesions. Growth and structural changes of lesions during pregnancy
      may occur with decidualization. Results on the association between pregnancy and
      symptoms of endometriosis are controversial and strongly biased. WIDER
      IMPLICATIONS: Available data on the development of endometriosis during and after
      pregnancy show fewer beneficial effects than previously reported. Therefore,
      women aiming for pregnancy on the background of endometriosis should not be told
      that pregnancy may be a strategy for managing symptoms and reducing progression
      of the disease.

PMID- 29471494
TI  - Morphological, Physiological, and Biochemical Responses of Two Tea Cultivars to
      Empoasca onukii (Hemiptera: Cicadellidae) Infestation.
AB  - The tea green leafhopper, Empoasca onukii Matsuda (Hemiptera: Cicadellidae), is
      an economically important pest of tea crops, Camellia sinensis (L.) O. Kuntze
      (Ericales: Theaceae), in China. The morphological, physiological, and biochemical
      changes of two tea cultivars, the normal green tea cultivar 'Fudingdabai' and the
      novel chlorophyll-deficient albino cultivar 'Huangjinya', infested by E. onukii
      were investigated to determine the tolerance of different tea cultivars to E.
      onukii attack. E.onukii infestation affected the growth of tea plants, and
      decreased the shoot length, leaf area, leaf thickness, and stem diameter. Also,
      E. onukii infestation lowered the thicknesses of upper epidermis, palisade
      tissue, and spongy tissue of leaves, and the parenchyma tissue thickness and pith
      diameter of stem internode. E.onukii infestation reduced the chlorophyll a, b and
      carotenoid contents within the leaves of 'Huangjinya,' which further influenced
      the photosynthetic rate. The maximum quantum yield and actual photochemical
      efficiency of photosystem II, and non-photochemical quenching in 'Huangjinya'
      were inhibited under E. onukii infestation. Peroxidase activity of E. onukii
      infested 'Huangjinya' increased more than superoxide dismutase and catalase. In
      addition, E. onukii feeding changed the contents of free amino acids, tea
      polyphenols, caffeine, and catechins in leaves of 'Huangjinya'. Overall, the
      light-induced albino cultivar 'Huangjinya' was susceptible to E. onukii while
      'Fudingdabai' was resistant.

PMID- 29471495
TI  - Arginine methylation of the C-terminus RGG motif promotes TOP3B topoisomerase
      activity and stress granule localization.
AB  - DNA topoisomerase 3B (TOP3B) is unique among all mammalian topoisomerases for its
      dual activities that resolve both DNA and RNA topological entanglements to
      facilitate transcription and translation. However, the mechanism by which TOP3B
      activity is regulated is still elusive. Here, we have identified arginine
      methylation as an important post-translational modification (PTM) for TOP3B
      activity. Protein arginine methyltransferase (PRMT) 1, PRMT3 and PRMT6 all
      methylate TOP3B in vitro at its C-terminal arginine (R) and glycine (G)-rich
      motif. Site-directed mutagenesis analysis identified R833 and R835 as the major
      methylation sites. Using a methylation-specific antibody, we confirmed that TOP3B
      is methylated in cells and that mutation of R833 and R835 to lysine (K)
      significantly reduces TOP3B methylation. The methylation-deficient TOP3B
      (R833/835K) is less active in resolving negatively supercoiled DNA, which
      consequently lead to accumulation of co-transcriptionally formed R-loops in vitro
      and in cells. Additionally, the methylation-deficient TOP3B (R833/835K) shows
      reduced stress granule localization, indicating that methylation is critical for
      TOP3B function in translation regulation. Mechanistically, we found that R833/835
      methylation is partially involved in the interaction of TOP3B with its auxiliary
      factor, the Tudor domain-containing protein 3 (TDRD3). Together, our findings
      provide the first evidence for the regulation of TOP3B activity by PTM.

PMID- 29471496
TI  - Should Acute Q-Fever Patients be Screened for Valvulopathy to Prevent
      Endocarditis?
AB  - Background: Echocardiographic screening of acute Q-fever patients and antibiotic
      prophylaxis for patients with cardiac valvulopathy is considered an important
      approach to prevent chronic Q-fever-related endocarditis. During a large Q-fever
      epidemic in the Netherlands, routine screening echocardiography was discontinued,
      raising controversy in the international literature. We followed a cohort of
      acute Q-fever patients to estimate the risk for developing chronic Q-fever, and
      we evaluated the impact of screening in patients who were not yet known to have a
      valvulopathy. Methods: The study population consisted of patients diagnosed with
      acute Q-fever in 2007 and 2008. We retrospectively reviewed all screening
      echocardiographs and checked for development of chronic Q-fever 8 years after the
      acute episode. Risks of developing chronic Q-fever in relation to the presence or
      absence of valvulopathy were analyzed with logistic regression. Results: The
      cohort included 509 patients, of whom 306 received echocardiographic screening.
      There was no significant difference (P-value = .22) in occurrence of chronic Q
      fever between patients with a newly detected valvulopathy (2/84, 2.4%) and those
      with no valvulopathy (12/202, 5.9%). Two patients with a newly detected
      valvulopathy, who did not receive antibiotic prophylaxis, developed chronic Q
      fever at a later stage. Conclusions: We found no difference in outcome between
      patients with and without a valvulopathy newly detected by echocardiographic
      screening. In retrospect, the 2 above-mentioned patients could have benefitted
      from antibiotic prophylaxis, but its omission must be weighed against the
      unnecessary large-scale and long-term use of antibiotics that would have resulted
      from universal echocardiographic screening.

PMID- 29471497
TI  - Increased NK Cell Function After Cessation of Long-Term Nucleos(t)ide Analogue
      Treatment in Chronic Hepatitis B Is Associated With Liver Damage and HBsAg Loss.
AB  - Background: Treatment with nucleos(t)ide analogues (NA) suppresses hepatitis B
      virus (HBV) DNA but rarely leads to functional cure of chronic hepatitis B (CHB).
      Following NA cessation, some hepatitis B e antigen (HBeAg)-negative CHB patients
      experience hepatitis B s antigen (HBsAg) loss. Cellular immune responses,
      including natural killer (NK) cell responses, explaining virological events
      following NA treatment cessation remain elusive. Methods: In a single-center
      prospective trial, 15 HBeAg-negative CHB patients on long-term NA treatment
      underwent structured NA cessation and were studied longitudinally. The NK cell
      compartment was assessed using high-dimensional flow cytometry and correlated
      with the clinical course. Results: Unsupervised stochastic neighbor embedding
      analysis revealed NA-treated CHB patients to have a significantly affected NK
      cell compartment compared to controls. Cessation of NA treatment resulted in
      minor phenotypic alterations, but it significantly augmented NK cell natural
      cytotoxicity responses in the CHB patients. This increased NK cell functionality
      correlated with alanine aminotransferase flares in the patients and was
      particularly enhanced in patients experiencing HBsAg seroclearance at long-term
      follow-up. Conclusions: Increased NK cell function is associated with active
      hepatitis and HBsAg seroclearance following structured NA cessation. This adds to
      our knowledge of the immunological events that develop following cessation of NA
      treatment in CHB.

PMID- 29471498
TI  - "It was the best worst day of my life": Narrative Content, Structure, and Process
      in Wisdom-Fostering Life Event Memories.
AB  - Objectives: The purpose of this study was to examine laypeople's subjective
      understanding of their own wisdom development. To do this, autobiographical
      memories of wisdom-fostering life events were examined for (a) life-event
      characteristics, and (b) self-reflective processes believed to support growth in
      wisdom through life experience. Methods: Midlife adults (N = 482) provided a
      written autobiographical memory of a wisdom-fostering life event. Memories were
      content analyzed by expert coders for life-event characteristics (i.e.,
      fundamentality, emotional valence, cultural normativity, and specific event
      types) and self-reflective processes (i.e., narrative coherence, meaning-making,
      and personal growth). Participants also completed self-report and performance
      measures of wisdom. Results: Wisdom-fostering life events tended to be
      fundamental to life, culturally non-normative, and emotionally negative.
      Participants frequently reported developing wisdom from relationship events
      (e.g., interpersonal conflict, divorce) and life-threatening/mortality events
      (e.g., death, serious illness). Wisdom was positively associated with
      reconstructive (i.e., narrative coherence) and analytical (i.e., meaning-making,
      personal growth) components of self-reflection. Self-reflective processes varied
      as a function of life-event characteristics. Discussion: This study emphasizes
      the role of both persons and environments in the development of wisdom, and
      highlights the importance of self-reflection as a mechanism through which wisdom
      is constructed from life experience.

PMID- 29471499
TI  - Mineral content of eggs differs with hen strain, age, and rearing environment.
AB  - Egg nutrient quality is strongly influenced by hen diet but is also affected by
      rearing environment, hen strain, and hen age. The objective of the current study
      was to determine the effect of: 1) conventional battery cages, 2) enrichable cage
      systems, 3) enriched colony housing, 4) cage-free, and 5) free-range rearing
      systems on mineral concentrations of whole, dried egg (yolk and albumen combined)
      from TA Tetra White (TW) and Hy-Line Brown (HB) hens at 44, 68, and 88 wk of age.
      We hypothesized that mineral concentration of eggs would differ among rearing
      systems but not between strains or with hen age. Hens held in enriched colony
      housing systems produced eggs with 10% lower Mg and 11% lower Mn levels than
      conventional hens. Concentrations of Ca and Cu were higher (7 and 8%,
      respectively) in eggs from TW hens than from HB hens. Eggs from HB hens had 8%
      higher concentrations of Fe, 6% higher Mg and 5% higher Mn than TW hens. Mn was
      higher in eggs from 44-wk hens than from 68- or 88-wk hens (16 and 11%,
      respectively). Interaction effects between rearing environment and hen age were
      observed for K and Mn concentrations. Eggs from 68-wk hens in conventional
      rearing systems contained 14 to 21% more K than eggs from conventional hens at 44
      and 88 wk and 14 to 18% more than eggs from 68-wk hens in other rearing systems.
      At 88 wk of age, hens in conventional rearing systems produced eggs with higher
      Mn concentration than hens in enrichable or enriched colony housing systems (22
      and 23%, respectively). Interactions between rearing environment, hen strain, and
      hen age were observed for egg Zn levels among 44- and 68-wk hens but were not
      detectable among 88-wk hens regardless of rearing system or hen strain. Observed
      differences in egg mineral content in our study were small and are unlikely to
      have substantial impact on human nutrition.

PMID- 29471500
TI  - Molecular Identification of Leishmania spp. in Sand Flies (Diptera: Psychodidae:
      Phlebotominae) in the Lencois Maranhenses National Park, Brazil.
AB  - Sand flies are very common in the region of Lencois Maranhenses National Park, an
      important tourist attraction in Brazil. However, the role of some species and
      their relative importance locally in Leishmania Ross 1903 transmission is
      unclear. The objective of this study was to identify Leishmania infection in
      phlebotomine sand flies collected around the Lencois Maranhenses National Park,
      an important conservation area and popular international/national tourist
      destination with a high incidence of leishmaniasis. Sand flies were collected in
      peridomiciliary areas on the tourist route from September 2012 to August 2013.
      The captured females were subjected to molecular analyses for the detection of
      Leishmania DNA. Sand flies were infected with four Leishmania species: Leishmania
      (Viannia) braziliensis (Vianna, 1911) was found in Lutzomyia whitmani (Antunes
      and Coutinho, 1939) (2.1%) and Lutzomyia longipalpis (Lutz and Neiva, 1912)
      (1.7%); Leishmania (Leishmania) infantum (Nicole, 1908) infected Lutzomyia
      wellcomei (Fraiha, Shaw, and Lainson, 1971) (20%), Lutzomyia sordellii (Shannon
      and Del Ponte, 1927) (4.3%), Lu. longipalpis (3.7%), and Lu. whitmani (0.8%);
      Leishmania (Leishmania) amazonensis (Lainson & Shaw, 1972) was found in Lu.
      whitmani (0.58%), while Leishmania (Viannia) lainsoni infected Lutzomyia evandroi
      (Costa Lima and Antunes, 1936) (3.4%), Lu. longipalpis (1.06%), and Lu. whitmani
      (0.29%). The occurrence of these parasites requires control measures to reduce
      the incidence of cutaneous leishmaniasis and to contain a possible epidemic of
      visceral leishmaniasis, the most severe form of the disease.

PMID- 29471501
TI  - Contemporary Ecological Interactions Improve Models of Past Trait Evolution.
AB  - Despite the fact that natural selection underlies both traits and interactions,
      evolutionary models often neglect that ecological interactions may, and in many
      cases do, influence the evolution of traits. Herein, we explore the
      interdependence of ecological interactions and functional traits in the
      pollination associations of hawkmoths and flowering plants. Specifically, we
      develop an adaptation of the Ornstein-Uhlenbeck model of trait evolution that
      allows us to study the influence of plant corolla depth and observed hawkmoth
      plant interactions on the evolution of hawkmoth proboscis length. Across diverse
      modelling scenarios, we find that the inclusion of contemporary interactions can
      provide a better description of trait evolution than the null expectation.
      Moreover, we show that the pollination interactions provide more-likely models of
      hawkmoth trait evolution when interactions are considered at increasingly fine
      scale groups of hawkmoths. Finally, we demonstrate how the results of best-fit
      modeling approaches can implicitly support the association between interactions
      and trait evolution that our method explicitly examines. In showing that
      contemporary interactions can provide insight into the historical evolution of
      hawkmoth proboscis length, we demonstrate the clear utility of incorporating
      additional ecological information to models designed to study past trait
      evolution.

PMID- 29471502
TI  - Elevated G6PD expression contributes to migration and invasion of hepatocellular
      carcinoma cells by inducing epithelial-mesenchymal transition.
AB  - Altered metabolism is one of the hallmarks of cancer cells. Pentose phosphate
      pathway (PPP) is a fundamental component of cellular metabolism. Glucose-6
      phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is elevated
      in many cancers and contributes to tumor growth by producing ribose-5-phosphate
      and NADPH through PPP. However, the role of G6PD in hepatocellular carcinoma
      (HCC) metastasis and the clinical significance of G6PD in HCC progression and
      prognosis have not been well determined. In this study, by investigating tissue
      samples from HCC patients and HCC cell lines, we found that elevated G6PD
      expression is significantly associated with HCC metastasis and poor prognosis of
      HCCs, and that knockdown of G6PD inhibits in vitro proliferation, migration and
      invasion of HCC cell lines. Further studies reveal that G6PD contributes to HCC
      migration and invasion of hepatocellular carcinoma cells by inducing epithelial
      mesenchymal transition through activation of signal transducer and activator of
      transcription 3 (STAT3) pathway. Our findings suggest that targeting G6PD could
      open up possibilities for metastasis intervention and improve the patients'
      outcomes for HCC.

PMID- 29471503
TI  - The role of the reprogramming method and pluripotency state in gamete
      differentiation from patient-specific human pluripotent stem cells.
AB  - The derivation of gametes from patient-specific pluripotent stem cells may
      provide new perspectives for genetic parenthood for patients currently facing
      sterility. We use current data to assess the gamete differentiation potential of
      patient-specific pluripotent stem cells and to determine which reprogramming
      strategy holds the greatest promise for future clinical applications. First, we
      compare the two best established somatic cell reprogramming strategies: the
      production of induced pluripotent stem cells (iPSC) and somatic cell nuclear
      transfer followed by embryonic stem cell derivation (SCNT-ESC). Recent reports
      have indicated that these stem cells, though displaying a similar pluripotency
      potential, show important differences at the epigenomic level, which may have
      repercussions on their applicability. By comparing data on the genetic and
      epigenetic stability of these cell types during derivation and in-vitro culture,
      we assess the reprogramming efficiency of both technologies and possible effects
      on the subsequent differentiation potential of these cells. Moreover, we discuss
      possible implications of mitochondrial heteroplasmy. We also address the ethical
      aspects of both cell types, as well as the safety considerations associated with
      clinical applications using these cells, e.g. the known genomic instability of
      human PSCs during long-term culture. Secondly, we discuss the role of the stem
      cell pluripotency state in germ cell differentiation. In mice, success in germ
      cell development from pluripotent stem cells could only be achieved when starting
      from a naive state of pluripotency. It remains to be investigated if the naive
      state is also crucial for germ cell differentiation in human cells and to what
      extent human naive pluripotency resembles the naive state in mouse.

PMID- 29471504
TI  - Anodyne by Design; Measuring the Prevalence of Esoteric Designer Opioids in Pain
      Management Patients.
AB  - The recent increase in illicit opioids sold on the black market, cut into heroin
      and masqueraded as prescription pills prompts a significant public health
      concern. Most designer opioids possess unknown potencies and unknown
      pharmacokinetics and their unregulated, variable dosages lead to rashes of
      overdoses. Additionally, many of the designer opioids, especially the fentanyl
      analogs are significantly more potent than heroin. High-profile cases involving
      overdoses of U-47700 and carfentanil have been reported in the media; however,
      the true prevalence of these and other designer opioids is unknown. Independent
      LC-MS-MS screen and confirmation methods have been developed and validated to
      identify and quantify fentanyl, and 18 designer opioids and their metabolites;
      methods were then exercised on urine specimens from contract pain management
      clients. Assuming patients in a pain management program may have a higher
      probability to seek out self-medication, samples from pain management patients
      were investigated for designer opioids. Similarly, pain management patients
      identified as using heroin may be more likely to experiment with or be
      accidentally exposed to designer opioids, specimens screening positive for the
      heroin metabolite 6-acetylmorphine were specifically chosen for designer opioid
      screening. Within this small group of pain management and heroin-positive
      samples, nine designer opioids were detected at a total prevalence of 25%. When
      screening random pain management samples not positive for heroin, a considerably
      lower percentage of samples (<1%) were identified as positive for designer
      opioids. Furanyl fentanyl, fluorobutyryl fentanyl and acetylfentanyl were the
      most prevalent designer opioids detected in both test groups.

PMID- 29471505
TI  - Involvement of cholinesterases in oxidative stress induced by chlorpyrifos in the
      brain of Japanese quail.
AB  - Chlorpyrifos is a widely used organophosphate pesticide (OP). In birds and
      mammals OP exhibits a toxic effect via inhibition of cholinesterases
      [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)] and through
      oxidative/nitrosative stress. In this study, the influence of chlorpyrifos on
      cholinesterase activity, parameters of oxidative stress [malondialdehyde (MDA);
      glutathione (GSH); superoxide dismutase (SOD); nitrite concentration (NO2-);
      hydrogen peroxide (H2O2)], and inflammatory parameter [activity of
      myeloperoxidase (MPO)] in the brain of Japanese quail (Coturnix japanica) was
      examined. The study was conducted on a total of 60 male Japanese quails (one
      control and 5 experimental groups, n = 10), 3 to 4 wk old. Quails were
      administered by gavage chlorpyrifos (CPF) for 7 consecutive da at doses of 0.375
      mg/kg BW, 0.75 mg/kg BW, 1.5 mg/kg BW, 3 mg/kg BW, and 6 mg/kg BW. Our studies
      have shown that all doses of CPF significantly inhibited both cholinesterases in
      brain: AChE from 22.74 to 37.83% and BChE from 19.53 to 61.9%, and that
      inhibition was dose dependent. Also, CPF has led to an increase in the
      concentration of MDA, GSH, NO2-, and H2O2 and activity of SOD and MPO. Overall,
      these results support the hypothesis that CPF causes oxidative stress and
      inflammatory response. This research was carried out on quails because there is
      hardly any or not enough data about the neurotoxic effect of CPF and especially
      about its influence on oxidative stress in birds. This study is highly important
      because we are witnessing massive avian mortality in certain countries due to
      pesticides.

PMID- 29471507
TI  - Di(2-Ethylhexyl) Phthalate Exposure During Prenatal Development Causes Adverse
      Transgenerational Effects on Female Fertility in Mice.
AB  - Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant and
      endocrine disrupting chemical, but little is known about its effects on female
      reproduction. Thus, we tested the hypothesis that prenatal exposure to DEHP
      accelerates the onset of puberty, disrupts estrous cyclicity, disrupts birth
      outcomes, and reduces fertility in the F1, F2, and F3 generations of female mice.
      Pregnant CD-1 mice were orally dosed with corn oil (vehicle control) or DEHP (20
      and 200 ug/kg/day and 500 and 750 mg/kg/day) from gestation day 10.5 until birth.
      F1 females were mated with untreated males to obtain the F2 generation. F2
      females were mated with untreated males to produce the F3 generation. In all
      generations, the onset of puberty, estrous cyclicity, select birth outcomes, and
      fertility-related indices were evaluated. In the F1 generation, prenatal DEHP
      exposure (200 ug/kg/day) accelerated the onset of puberty, it (200 ug and 500
      mg/kg/day) disrupted estrous cyclicity, and it (20 and 200 ug/kg/day) decreased
      fertility-related indices. In the F2 generation, ancestral DEHP exposure (500
      mg/kg/day) accelerated the onset of puberty, it (20 and 200 ug/kg/day) disrupted
      estrous cyclicity, it (20 ug and 500 mg/kg/day) increased litter size, and it
      (500 mg/kg/day) decreased fertility-related indices. In the F3 generation,
      ancestral DEHP exposure (20, 200 ug, and 500 mg/kg/day) accelerated the onset of
      puberty, it (20 ug/kg/day) disrupted estrous cyclicity, and it (750 mg/kg/day)
      decreased female pup anogenital index. Collectively, these data indicate that
      prenatal DEHP exposure causes female reproductive problems in a multigenerational
      and transgenerational manner.

PMID- 29471508
TI  - Protein hydrolysate from turkey meat and optimization of its antioxidant
      potential by response surface methodology.
AB  - The objective of this research was to optimize antioxidant potential of
      hydrolyzed protein using Flavourzyme assisted hydrolysis of turkey meat and
      compare the antioxidant activity of hydrolysates from turkey meat, chicken, and
      beef. Response surface methodology (RSM) was used to determine the optimal
      Flavourzyme hydrolysis conditions for preparation of hydrolysate from turkey
      meat, which were at a temperature of 50.09 degrees C, pH of 5.42, and processing
      time of 1.08 hours. For comparison, antioxidant activities of the hydrolysate
      from turkey meat, chicken, and beef under the optimum conditions were determined
      using reducing power, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)
      (ABTS) radical cation, hydroxyl radical, and 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      radical scavenging activities. The antioxidant activity of turkey meat and
      chicken meat was significantly higher than that of beef (P < 0.05). Therefore
      Flavourzyme could be regarded as an effective hydrolytic enzyme for preparation
      of antioxidant hydrolysate from turkey meat, indicating the potential use of it
      as a functional food ingredient with shelf-life extension purposes.

PMID- 29471506
TI  - A translational silencing function of MCPIP1/Regnase-1 specified by the target
      site context.
AB  - The expression of proteins during inflammatory and immune reactions is
      coordinated by post-transcriptional mechanisms. A particularly strong suppression
      of protein expression is exerted by a conserved translational silencing element
      (TSE) identified in the 3' UTR of NFKBIZ mRNA, which is among the targets of the
      RNA-binding proteins Roquin-1/2 and MCPIP1/Regnase-1. We present evidence that in
      the context of the TSE MCPIP1, so far known for its endonuclease activity toward
      mRNAs specified by distinct stem-loop (SL) structures, also suppresses
      translation. Overexpression of MCPIP1 silenced translation in a TSE-dependent
      manner and reduced ribosome occupancy of the mRNA. Correspondingly, MCPIP1
      depletion alleviated silencing and increased polysomal association of the mRNA.
      Translationally silenced NFKBIZ or reporter mRNAs were mostly capped,
      polyadenylated and ribosome associated. Furthermore, MCPIP1 silenced also cap
      independent, CrPV-IRES-dependent translation. This suggests that MCPIP1
      suppresses a post-initiation step. The TSE is predicted to form five SL
      structures. SL4 and 5 resemble target structures reported for MCPIP1 and together
      were sufficient for MCPIP1 binding and mRNA destabilization. Translational
      silencing, however, required SL1-3 in addition. Thus the NFKBIZ TSE functions as
      an RNA element in which sequences adjacent to the site of interaction with MCPIP1
      and dispensable for accelerated mRNA degradation extend the functional repertoire
      of MCPIP1 to translational silencing.

PMID- 29471509
TI  - Reply: The Crus exhibits stronger functional connectivity with executive network
      nodes than with the default mode network.

PMID- 29471510
TI  - Moderator's view: Low-protein diet in chronic kidney disease: effectiveness,
      efficacy and precision nutritional treatments in nephrology.
AB  - Intention-to-treat and per-protocol analyses provide complementary information
      about the usefulness of therapies. While intention-to-treat analyses of trials
      that tested low-protein diets remain debated, per-protocol analyses of the same
      trials show that low protein intake actually reduces the risk of kidney failure.
      Per-protocol analyses are notoriously open to bias but intention-to-treat
      analyses are less immaculate than commonly realized because they critically
      depend on adherence to the treatment being tested and therefore may not be
      directly relevant for informing clinical decisions when different degrees of
      adherence to therapy occur. Over the last 20 years new statistical techniques
      censoring patients at the time when they become uncompliant and that adjust for
      confounding attributable to incomplete adherence, i.e. for prognostic factors
      that predict adherence to treatment, have been developed. These techniques can be
      usefully applied to reanalyse the Modification Diet in Renal Disease (MDRD) and
      other trials. Intensive surveillance of patients on a low-protein diet is
      fundamental for early detection of malnutrition. However, the resources demanded
      by such surveillance are likely superior to the actual dietitians workforce
      dedicated to follow-up of the chronic kidney disease (CKD) population.
      Surveillance efforts may perhaps be preferentially devoted to preselected
      patients, i.e. patients that maintain good compliance and an adequate metabolic
      and nutritional status, while patients who are resistant to educational efforts
      and show persisting uncompliance may be reallocated to a diet with a higher
      protein content, which poses a lower risk of malnutrition and other adverse
      health outcomes.

PMID- 29471511
TI  - Sexual Dimorphism in the Behavioral Responses and the Immunoendocrine Status in d
      Galactose-Induced Aging.
AB  - For almost 20 years, chronic systemic d-galactose, a monosaccharide abundantly
      present in milk products, fruits, and vegetables, has been used as a tool to
      achieve models of accelerated aging. Its neurotoxicity, induced by abnormal
      accumulation of reactive oxygen species and advanced glycation end products, has
      been widely reported. However, behavioral outcomes are still controversial and
      little is known about sex-dependent vulnerability. We performed a comprehensive
      behavioral and multifunctional screening of the chronic effects of low (50 mg/kg)
      and high (100 mg/kg) doses of d-galactose in 6-month-old male and female gold
      standard C57BL/6 mice. Twelve classical tests with convergent validity analyzed
      sensorimotor, emotional and cognitive domains, indicating the existence of
      thresholds of response. Distinct vulnerability patterns were found in a selective
      sex- and dose-dependent manner. In males, d-galactose induced sensorimotor
      impairment and immunoendocrine senescence, but the low dose resulted in improved
      learning and memory. Oppositely, d-galactose-treated females exhibited a dose
      dependent worse motor and spatial learning, but improved memory. Behavioral
      outcome items point at distinct neuronal substrates underlying the functional
      capacity of d-galactose-treated animals to meet task-dependent performance
      demands. They support that males and females can be regarded as two exceptional
      natural scenarios to study the functional interplay in the cross talk of
      homeostatic networks in aging.

PMID- 29471513
TI  - The genetic correlation between scapula shape and shoulder lesions in sows.
AB  - Shoulder lesions and body condition of sows at weaning have both environmental
      and genetic causes. The traits can be scored at farm level, and following
      recording, the traits can be included in the breeding goal and directional
      selection can be applied. However, to further increase the genetic progress of
      these traits, it is advantageous to develop indicator traits on the selection
      candidates (test boars or gilts, not yet exhibiting the phenotype themselves). It
      has previously been suggested that the scapula morphology and the spine of
      scapula might be a key factor for the sow to develop shoulder lesions. In this
      study, we developed 11 novel traits describing the morphology of the shoulder
      blade based on computed tomography images from scanned test boars. These traits
      include the area, length, width, height, and volume of the shoulder blade as well
      as 6 traits obtained from principal component analysis, describing 80% of the
      variation observed for the scapula spine profile. The analyzed traits have
      moderate to high heritability (h2 from 0.29 to 0.78, SE = 0.06), low to medium
      genetic correlations with shoulder lesions (up to 0.4, SE = 0.1), and body
      condition scoring at weaning (up to 0.25, SE = 0.1). These novel phenotypes can
      now be recorded automatically and accurately prior to selection of the AI boars.
      If such recordings are included in multivariate genomic selection models, it is
      expected to improve the genetic progress of shoulder lesions and body condition
      score by weaning.

PMID- 29471514
TI  - Management of anaemia and iron deficiency in patients with cancer: ESMO Clinical
      Practice Guidelines.

PMID- 29471515
TI  - Corrigendum: Association between intraoral pressure and molar position and
      inclination in subjects with facial asymmetry.

PMID- 29471516
TI  - Optical spectral transmission to assess inflammation in hand and wrist joints of
      rheumatoid arthritis patients.
AB  - Objective: To develop an optical spectral transmission (OST) model to measure
      joint inflammation, and thus disease activity, as well as to evaluate (patho
      )physiological findings that could lead to misclassification of inflammation.
      Methods: Forty-six RA patients were included in this cross-sectional study, where
      US scores, duplicate OST measurements and 28-joint DAS (DAS28) were acquired.
      With US as a reference standard, the diagnostic performance of OST in detecting
      inflammation at the joint level was evaluated using receiver operating
      characteristic (ROC) curve analyses. At the patient level, correlations with US
      were analysed for DAS28 and OST, and at joint level for OST and tender and
      swollen joint counts (TJC and SJC, respectively). Joint pathology potentially
      influencing misclassification by OST [erosions, osteophytes, tendon (sheath)
      inflammation (ab)normal vasculature and chondrocalcinosis] was evaluated for
      significance in a multivariate nominal logistic regression model. Results:
      Diagnostic performance of OST was good for MCP [area under the ROC curve (AUC
      ROC) 0.88], PIP (AUC-ROC 0.83) and wrist (AUC-ROC 0.74) joints and for all joints
      together (AUC-ROC 0.85). At the patient level, DAS28 correlated very poorly (rho
      = 0.06) and OST moderately (rho = 0.54) with US. At the joint level, US
      correlation with OST was strong (rho = 0.64), with SJC it was weak (rho = 0.30)
      and with TJC it was very weak (rho = -0.02). Misclassification of inflammation by
      OST was relatively rare (17%). Dorsal erosions [odds ratio (OR) 4.0], osteophytes
      (OR 2.1) and extensor tendinitis (OR 4.6) increased the risk of underestimating
      inflammation of MCP and PIP joints and osteophytes (OR 3.0) also increased the
      risk of overestimating inflammation. Conclusion: OST is a sensitive, specific and
      objective technique to assess joints inflammation of the hands and wrists of RA
      patients, even though bone and tendon pathology increases the risk of
      misclassification.

PMID- 29471517
TI  - The role of the ground-glass opacity ratio in resected lung adenocarcinoma.
AB  - OBJECTIVES: The goal of this study was to investigate the role of the ground
      glass opacity (GGO) ratio in lung adenocarcinoma in predicting surgical outcomes.
      METHODS: Patients who underwent surgical resection for pulmonary adenocarcinoma
      between January 2004 and December 2013 were reviewed. The clinical data, imaging
      characteristics of nodules, surgical approaches and outcomes were analysed with a
      mean follow-up of 87 months. RESULTS: Of 789 enrolled patients, 267 cases were
      categorized as having a GGO ratio >=0.75; 522 cases were categorized as having a
      GGO ratio <0.75. The gender, tumour differentiation, epidermal growth factor
      receptor mutation, smoking habits, lymphovascular space invasion, tumour size,
      maximum standard uptake value and carcinoembryonic antigen levels were
      significantly different in the 2 groups. In the group with a GGO ratio >=0.75,
      63.3% of the patients underwent sublobar resection (18.8% with a GGO ratio <
      0.75, P <0.001). These patients had fewer relapses (2.2% for GGO ratio >=0.75,
      26.8% for GGO ratio <0.75, P < 0.001) and a better 5-year survival rate (95.5%
      for GGO ratio >=0.75, 77.4% for GGO ratio <0.75, P < 0.001). None of the patients
      with a GGO ratio >=0.75 had lymph node involvement. The multivariable Cox
      regression analysis revealed that a GGO ratio <0.75 was an independent factor for
      postoperative relapse with a hazard ratio of 3.96. CONCLUSIONS: A GGO ratio
      >=0.75 provided a favourable prognostic prediction in patients with resected lung
      adenocarcinoma. Sublobar resection and lymph node sampling revealed a fair
      outcome regardless of tumour size. However, anatomical resection is still the
      standard approach for patients with tumours with a GGO ratio <0.75, size >2 cm.

PMID- 29471518
TI  - Differences between Supportive Music and Imagery and Music Listening during
      Outpatient Chemotherapy and Potential Moderators of Treatment Effects.
AB  - Background: Supportive music and imagery and music listening interventions have
      been effective in decreasing distress and improving mood in cancer patients
      receiving chemotherapy, but it is unclear whether the two interventions differ in
      their treatment benefits. Furthermore, previous studies have not examined
      moderators to determine which subgroup(s) of patients may benefit most from each
      intervention. Objective: To examine the effects of supportive music and imagery
      compared with preferred music listening on responsiveness to music therapy,
      distress, anxiety and depression, and benefit finding. A secondary purpose was to
      explore sense of coherence and locus of control as potential moderators of
      intervention effectiveness. Methods: A single-session, two-group comparative
      effectiveness randomized trial in two cancer centers. Patients were randomized to
      supportive music and imagery or preferred music listening during outpatient
      chemotherapy treatment. Data were collected at baseline and immediately after the
      45-minute session. ANCOVA models were used to determine main effects of
      intervention as well as pairing potential moderators with group assignment to
      explore differences in intervention effects by moderator. Results: There were
      differential effects between the two interventions with the supportive music and
      imagery group scoring higher in responsiveness to music therapy and benefit
      finding. The music listening group scores indicated lower distress. The
      exploratory moderating analyses suggested Health Locus of Control-Internal and
      Sense of Coherence influenced intervention effectiveness. Conclusions: Music and
      imagery and preferred music listening experiences may serve different therapeutic
      purposes, access and activate different patient resources, and may be helpful at
      different stages of treatment.

PMID- 29471519
TI  - Higher Risk of Abdominal Obesity, Elevated Low-Density Lipoprotein Cholesterol,
      and Hypertriglyceridemia, but not of Hypertension, in People Living With Human
      Immunodeficiency Virus (HIV): Results From the Copenhagen Comorbidity in HIV
      Infection Study.
AB  - Background: People living with human immunodeficiency virus (PLWH) are
      characterized by excess risk of cardiovascular diseases (CVD) and CVD risk
      factors compared to uninfected individuals. We investigated the association
      between HIV infection and abdominal obesity, elevated low-density lipoprotein
      cholesterol (LDL-C), hypertriglyceridemia, and hypertension in a large cohort of
      predominantly well-treated PLWH and matched controls. Methods: 1099 PLWH from the
      Copenhagen Co-morbidity in HIV Infection Study and 12 161 age- and sex-matched
      uninfected controls from the Copenhagen General Population Study were included
      and underwent blood pressure, waist, hip, weight, and height measurements and
      nonfasting blood samples. We assessed whether HIV was independently associated
      with abdominal obesity, elevated LDL-C, hypertriglyceridemia, and hypertension
      using logistic regression models adjusted for known risk factors. Results: HIV
      infection was associated with higher risk of abdominal obesity (adjusted odds
      ratio [aOR], 1.92 [1.60-2.30]) for a given body mass index, elevated LDL-C (aOR,
      1.32 [1.09-1.59]), hypertriglyceridemia (aOR, 1.76 [1.49-2.08]), and lower risk
      of hypertension (aOR, 0.63 [0.54-0.74]). The excess odds of abdominal obesity in
      PLWH was stronger with older age (p interaction, 0.001). Abdominal obesity was
      associated with elevated LDL-C (aOR, 1.44 [1.23-1.69]), hypertension (aOR, 1.32
      [1.16-1.49]), and hypertriglyceridemia (aOR, 2.12 [1.86-2.41]). Conclusions:
      Abdominal obesity was associated with proaterogenic metabolic factors including
      elevated LDL-C, hypertension, and hypertriglyceridemia and remains a distinct HIV
      related phenotype, particularly among older PLWH. Effective interventions to
      reduce the apparent detrimental impact on cardiovascular risk from this phenotype
      are needed.

PMID- 29471520
TI  - Effect of exposure to second-hand smoke from husbands on biochemical
      hyperandrogenism, metabolic syndrome and conception rates in women with
      polycystic ovary syndrome undergoing ovulation induction.
AB  - STUDY QUESTION: Does second-hand smoke (SHS) exposure from husbands have adverse
      effects on sex hormones, metabolic profiles, clinical phenotypes and fertility
      outcomes in women with polycystic ovary syndrome (PCOS) undergoing ovulation
      induction? SUMMARY ANSWER: SHS exposure is associated with worsened biochemical
      hyperandrogenism, higher incidence of metabolic syndrome and reduced conception
      rates in women with PCOS. WHAT IS KNOWN ALREADY: Smoking in women impairs
      fecundity at some stages of the reproductive process including folliculogenesis,
      embryo transport, endometrial angiogenesis and uterine blood flow. Yet little is
      known about the hazard of SHS exposure in women with PCOS. STUDY DESIGN, SIZE,
      DURATION: This study was a secondary analysis of the Polycystic Ovary Syndrome
      Acupuncture and Clomiphene Trial (PCOSAct), a large randomized controlled trial
      conducted at 27 hospitals from 2012 to 2015 in mainland China.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Out of 1000 women with PCOS, SHS
      exposure status were available in 500 women, of whom 271 women were non-exposed
      and 229 exposed to cigarette smoke (170 women <=10 cigarettes per day as low-SHS
      exposed and 59 women >10 cigarettes per day as high-SHS exposed). We compared
      circulating sex steroids, glucose and lipid metabolism, metabolic syndrome and
      phenotypes, fertility and obstetric outcomes between non-exposed and exposed
      women. MAIN RESULTS AND THE ROLE OF CHANCE: Women exposed to SHS, compared to non
      exposed women, had a higher serum total testosterone (1.7 vs 1.5 nmol/L, P =
      0.01), free androgen index (5.7 vs 4.0, P = 0.001) and lower sex hormone binding
      globulin (30.1 vs 35.6 nmol/L, P = 0.03). Metabolic syndrome, but not other
      phenotypes, was more frequent in exposed women as compared to non-exposed women
      (21.8 vs 13.3%, adjusted odds ratio (OR)=1.66; 95% CI, 1.02-2.71, P = 0.04).
      Ovulation rates between exposed and non-exposed groups were not significantly
      different (76.9 vs 82.9%, adjusted OR=0.72; 95% CI, 0.45-1.15, P = 0.17).
      Conception rates were significant lower in the exposed group (26.6 vs 36.9%;
      adjusted OR=0.61; 95% CI, 0.41-0.91; P = 0.01), while clinical pregnancy and live
      birth rates showed a similar trend that was not statistically significant.
      Gestational age, birth weight and other obstetric outcomes were not affected by
      SHS exposure. LIMITATIONS, REASONS FOR CAUTION: Data on SHS exposure were missing
      in 50% of the women. We did not assay serum nicotine or cotinine levels to
      quantify the SHS exposure status. WIDER IMPLICATIONS OF THE FINDINGS: These data
      suggest that smoking partners of infertile women with PCOS who seek treatment
      should be advised to quit smoking. STUDY FUNDING/COMPETING INTEREST(S): Funding
      was provided by the National Public Welfare Projects for Chinese Medicine
      (201107005 and 200807002) and the National Clinical Trial Base in Chinese
      Medicine Special Projects (JDZX2012036 and 2015B009). There are no conflicts of
      interest. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov number: NCT01573858 and
      chictr.org.cn number: ChiCTR-TRC-12002081.

PMID- 29471521
TI  - Variable response of nirK and nirS containing denitrifier communities to long
      term pH manipulation and cultivation.
AB  - Denitrification is a key process responsible for the majority of soil nitrous
      oxide (N2O) emissions but the influences of pH and cultivation on the soil
      denitrifier community remain poorly understood. We hypothesised that the
      abundance and community structure of the total bacterial community and bacterial
      denitrifiers would be pH sensitive and that nirK and nirS containing denitrifiers
      would differ in their responses to change in pH and cultivation. We investigated
      the effect of long-term pH-adjusted soils (ranging from pH 4.2 to 6.6) under
      different lengths of grass cultivation (one, two and three years of ley grass) on
      the general bacterial and denitrifier functional communities using 16S rRNA, nirK
      and nirS genes as markers. Denitrifier abundance increased with pH, and at pH
      below 4.7 there was a greater loss in nirS abundance per unit drop in pH than
      soils above this threshold pH. All community structures responded to changes in
      soil pH, while cultivation only influenced the community structure of nirK. These
      differences in denitrifier responses highlight the importance of considering both
      nirK and nirS gene markers for estimating denitrifier activity. Identifying such
      thresholds in response of the microbial community to changes in pH is essential
      to understanding impacts of management or environmental change.

PMID- 29471522
TI  - PRMT-5 converts monomethylarginines into symmetrical dimethylarginines in
      Caenorhabditis elegans.

PMID- 29471523
TI  - Liver transcriptomic and plasma metabolomic profiles of fattening lambs are
      modified by feed restriction during the suckling period.
AB  - The increasing world population is driving demand for improved efficiency of feed
      resources of livestock. However, the molecular mechanisms behind various feed
      efficiency traits and their regulation by nutrition remain poorly understood.
      Here, we aimed to identify differentially expressed (DE) genes in the liver
      tissues of fattening Merino lambs and differences in metabolites accumulated in
      plasma to identify modified metabolic pathways as a consequence of milk
      restriction during the suckling period. Twenty-four male Merino lambs (4.81 +/-
      0.256 kg) were divided into 2 groups (n = 12 per dietary treatment). The first
      group (ad libitum, ADL) was kept permanently with the dams, whereas the other
      group (restricted, RES) was milk restricted. When they reached 15 kg of live body
      weight (LBW), all the animals were offered the same complete pelleted diet at the
      same level (35 g DM/kg LBW per day) to ensure no differences in dry matter
      intake. All the lambs were harvested when they reached 27 kg of LBW. For
      transcriptomic analysis, 4 liver samples from each group (8 samples in total)
      were selected for RNA sequencing (RNA-seq), and plasma samples from all animals
      (24 samples in total) were used to perform a nontargeted metabolomic analysis on
      a hybrid quadrupole-time-of-flight mass spectrometer coupled to an ultra-high
      performance liquid chromatographic system (UHPLC/QTOF-MS). Thirty-eight DE
      annotated genes were identified by RNA-seq, with 23 DE genes being down-regulated
      and 15 up-regulated in the liver of RES lambs relative to the ADL group (P <
      0.10). Also, the metabolomic assay identified 38 differentially accumulated
      compounds (P < 0.10). In general, those genes and pathways involved in protein
      synthesis or protease inhibitors were down-regulated in the RES group, whereas
      those related to proteolytic degradation were up-regulated, thus suggesting a
      higher catabolism of proteins in these lambs. RES lambs showed over-expression of
      xenobiotic metabolism pathways, whereas those genes related to beta-oxidation of
      fatty acids were down-regulated. According to the data obtained, early feed
      restriction during the suckling period of Merino lambs promoted long-term effects
      on both the hepatic transcriptomic profile and plasma metabolic profile, which
      might have modified fatty acids metabolism, catabolism of proteins, and
      detoxification of xenobiotics, thus reducing feed efficiency during the fattening
      period.

PMID- 29471525
TI  - Rightsizing root phenotypes for drought resistance.
AB  - I propose that reduced root development would be advantageous for drought
      resistance in high-input agroecosystems. Selection regimes for crop ancestors and
      landraces include multiple stresses, intense competition, and variable resource
      distribution, which favored prolific root production, developmental plasticity in
      response to resource availability, and maintenance of unspecialized root tissues.
      High-input agroecosystems have removed many of these constraints to root
      function. Therefore, root phenotypes that focus on water capture at the expense
      of ancestral adaptations would be better suited to high-input agroecosystems.
      Parsimonious architectural phenotypes include fewer axial roots, reduced density
      of lateral roots, reduced growth responsiveness to local resource availability,
      and greater loss of roots that do not contribute to water capture. Parsimonious
      anatomical phenotypes include a reduced number of cortical cell files, greater
      loss of cortical parenchyma to aerenchyma and senescence, and larger cortical
      cell size. Parsimonious root phenotypes may be less useful in low-input
      agroecosystems, which are characterized by multiple challenges and trade-offs for
      root function in addition to water capture. Analysis of the fitness landscape of
      root phenotypes is a complex challenge that will be aided by the development of
      robust functional-structural models capable of simulating the dynamics of root
      soil interactions.

PMID- 29471524
TI  - Enteric methane production and ruminal fermentation of forage brassica diets fed
      in continuous culture.
AB  - The aim of the current study was to determine nutrient digestibility, VFA
      production, N metabolism, and CH4 production of canola (Brassica napus L.),
      rapeseed (B. napus L.), turnip (Brassica rapa L.), and annual ryegrass (Lolium
      multiflorum Lam.) fed with orchardgrass (Dactylis glomerata L.) in continuous
      culture. Diets were randomly assigned to fermentors in a 4 * 4 Latin square
      design using 7 d for adaptation and 3 d for collection. Diets were: 1) 50%
      orchardgrass + 50% annual ryegrass (ARG); 2) 50% orchardgrass + 50% canola (CAN);
      3) 50% orchardgrass + 50% rapeseed (RAP); and 4) 50% orchardgrass + 50% turnip
      (TUR). Feedings (82 g DM/d) occurred four times daily throughout 4, 10-d periods
      at 730, 1030, 1400, and 1900 h. Methane samples were collected every 10 min using
      a photoacoustic gas analyzer (LumaSense Technologies, Inc.; Santa Clara, CA)
      during the last 3 d of the experiment. Effluent samples were collected on d 8, 9,
      and 10, composited by fermentor, and analyzed for VFA and pH as well as DM, OM,
      CP, and fiber fractions for determination of nutrient digestibility. Forage
      samples were analyzed for CP, NDF, ADF, minerals, and glucosinolate (GLS)
      concentrations. Data were analyzed using the GLIMMIX procedure of SAS. Apparent
      DM, OM, and NDF digestibilities and true DM and OM digestibilities were similar
      (P > 0.28) among diets (45.1, 63.2, 44.1, 67.1, and 87.2%, respectively). Total
      VFA (87.2 mol/100 mol), pH (6.47), and acetate (A: 44.6 mol/100 mol) were also
      not different (P > 0.20) among diets. The A:P (P = propionate) ratio was greater
      (P < 0.01) in ARG and CAN than RAP and TUR. Daily CH4 production was greater (P <
      0.01) in ARG than all other diets (68.9 vs. 11.2 mg/d). Methane, whether
      expressed as g per g of OM, NDF, digestible OM, or digestible NDF fed was
      greatest (P < 0.01) in ARG but similar (P > 0.18) among brassica diets. A
      significant negative correlation was observed between total GLS and CH4
      production. However, when multiple regression analysis on CH4 production was
      completed, neither total GLS nor individual GLS were a significant component of
      the model. Addition of brassicas provided similar nutrient digestibility to ARG
      while reducing daily CH4 production, potentially making brassicas an alternative
      for ARG in pasture-based ruminant diets.

PMID- 29471526
TI  - Predictors and Outcomes of Mealtime Emotional Climate in Families With
      Preschoolers.
AB  - Objective: Mealtime emotional climate (MEC) is related to parent feeding and
      mental health, and possibly to child food consumption. However, MEC has been
      inconsistently assessed with a variety of coding schemes and self-report
      instruments, and has not been examined longitudinally. This study aims to
      characterize MEC systematically using an observational, count-based coding
      scheme; identify whether parent feeding or mental health predict MEC; and examine
      whether MEC predicts child food consumption and weight. Methods: A subsample of
      parents (n = 74) recruited from a larger study completed questionnaires when
      children were about 37 months, participated in a home visit to videotape a
      mealtime when children were about 41 months, and completed questionnaires again
      when children were about 51 months old. Maternal and child positive and negative
      emotions were coded from videotaped mealtimes. Observational data were submitted
      to cluster analyses, to identify dyads with similar emotion expression patterns,
      or MEC. Logistic regression was used to identify predictors of MEC, and Analysis
      of Covariance was used to examine differences between MEC groups. Results: Dyads
      were characterized as either Positive Expressers (high positive, low negative
      emotion) or All Expressers (similar positive and negative emotion). Increased
      food involvement feeding practices were related to decreased likelihood of being
      an All Expresser. Positive Expressers reported that their children ate more
      healthy food, compared with All Expressers. Conclusions: Observed MEC is driven
      by maternal emotion, and may predict child food consumption. Food involvement may
      promote positive MEC. Improving MEC may increase child consumption of healthy
      foods.

PMID- 29471527
TI  - The Heterogeneity Between Lynch-Associated and Sporadic MMR Deficiency in
      Colorectal Cancers.
AB  - Background: Previous studies demonstrated that prognosis of germline deficiency
      in mismatch repair protein (dMMR) was different from that of sporadic dMMR. The
      underlying mechanism has not been studied. Methods: From a prospectively
      maintained database, we collected dMMR colorectal cancer (CRC) patients
      identified by postoperative immunohistochemistry screening. According to genetic
      test, patients were grouped as Lynch-associated or sporadic dMMR. We compared the
      clinical-pathological features, prognosis, and immunoreactive differences between
      the two groups. By whole-exome sequencing and neoantigen detection pipeline,
      mutational frequencies and neoantigen burdens were also compared. All statistical
      tests were two-sided. Results: Sixty-seven sporadic dMMR and 85 Lynch-associated
      CRC patients were included in the study. Sporadic dMMR patients were older (P <
      .001) and their tumors were poorly differentiated (P = .03). The survival was
      better in the Lynch-associated group (P = .001). After adjustment, the difference
      still remained statistically significant (hazard ratio = 0.29, 95% confidence
      interval = 0.09 to 0.95, P = .04). The scores of Crohn's-like reaction (CRO; P <
      .001), immunoreactions in the invasive margin (IM; P = .01), tumor stroma (TS; P
      = .009), and cancer nest (CN; P = .02) of the Lynch-associated group were
      statistically significantly higher. The numbers of CD3+, CD8+, Foxp3+ tumor
      infiltrating lymphocytes (TILs) in IM; CD3+, CD4+ TILs in TS; and CD3+, CD4+,
      CD8+ TILs in CN were statistically significantly higher in Lynch-associated dMMR
      patients. Based on the 16 patients who under went whole-exome sequencing, there
      were also more somatic mutations and neoantigen burdens in the Lynch-associated
      group compared with the sporadic dMMR group (439/pt vs 68/pt, P = .006; 628/pt vs
      97/pt, P = .009). Conclusions: There are heterogeneities in dMMR CRCs. Lynch
      associated dMMR patients present with more somatic mutations and neoantigens
      compared with sporadic dMMR, which probably results in stronger immunoreactions
      and survival improvement.

PMID- 29471530
TI  - Awake Brain Mapping in Dominant Side Insular Glioma Surgery: 2-Dimensional
      Operative Video.

PMID- 29471531
TI  - Carbon monoxide poisoning in wood pellet storerooms.
AB  - Background: Carbon monoxide is the leading cause of mortality from unintentional
      poisoning in Slovenia. It has been shown that carbon monoxide levels can rise in
      wood pellet storerooms because of chemical degradation of pellets, even at room
      temperature. We present a case of lethal carbon monoxide poisoning with first
      responder carbon monoxide exposure. Aims: To highlight the dangers rescuers face
      during interventions in pellet storerooms and the need for preventive
      precautions. Case report: Paramedics and firemen were called to help an
      unconscious man in a wood pellet storeroom. Firemen immediately evacuated the
      victim and paramedics began cardiopulmonary resuscitation. Soon after, rescuers
      complained of dizziness and developed headache, nausea and fatigue. A carbon
      monoxide level of 600 ppm was detected. Three rescuers were treated with 100%
      oxygen. Blood carboxyhaemoglobin levels were up to 8% on arrival at the emergency
      department. The victim died and autopsy confirmed carbon monoxide poisoning.
      Conclusions: First responders have to be aware of the dangers of carbon monoxide
      in wood pellet storerooms. Basic precautions and safety instructions should be
      followed before entering a wood pellet storeroom. Carbon monoxide should be
      measured before entering and self-contained breathing apparatus should be used.
      Wood pellet storerooms require continuous ventilation and should be equipped with
      carbon monoxide detectors.

PMID- 29471532
TI  - Hyperparasitism and Non-Nidicolous Mating by Male Ixodes angustus Ticks (Acari:
      Ixodidae).
AB  - Ixodes angustus (Neumann) (Acari: Ixodidae) is considered to be a nidicolous tick
      in that the entire life cycle can be completed in the host nest. Males of this
      tick have been reported to be rare on hosts because most mating occurs in the
      host nest and males typically do not feed on hosts. Collections of I. angustus in
      Alaska departed slightly from this paradigm in that nine males were collected
      from hosts, mostly in copulation with females that were attached to mammalian
      hosts. Non-nidicolous mating was therefore more common in I. angustus collected
      in this study than has been reported previously. A hyperparasitic male I.
      angustus was found firmly attached via its hypostome and chelicerae to the
      ventral idiosoma of a partially engorged female I. angustus that was attached to,
      and feeding on, an American red squirrel, Tamiasciurus hudsonicus (Erxleben).
      This hyperparasitic interaction is discussed and illustrated with a Scanning
      Electron Micrograph.

PMID- 29471533
TI  - Reproducibility of work ability and work functioning instruments.
AB  - Background: Work ability (WA) and work functioning (WF) instruments can be useful
      in occupational health practice. The reproducibility of both instruments is
      important to their relevance for daily practice. Clinimetrics concerns the
      methodological and statistical quality of instruments and their performance in
      practice. Aims: To assess the reproducibility of WA and WF instruments. Methods:
      Dutch workers completed a questionnaire containing WA questions and the WF
      questionnaire twice with a 7-day interval between. The questionnaire included an
      appraisal of current general, physical and mental/emotional WA (0-10) and the
      composite WF questionnaire of 49 items (0-100). We measured reproducibility,
      reliability and agreement by calculating the intraclass correlation coefficient
      (ICC), the standard error of measurement (SEM) and the smallest detectable change
      (SDC). Results: The answers of 104 respondents were available for analysis.
      General, physical and mental/emotional WA had ICC values of 0.52, 0.69 and 0.56,
      respectively. For WF, the ICC value was 0.85. For general WA, the SEM was 0.71.
      For physical and mental/emotional WA, the SEMs were 0.75 and 0.74, respectively.
      For general, physical and mental/emotional WA, the SDC was 1.98, 2.09 and 2.05
      respectively. The SEM of the WF score was 4.78, and the SDC was 13.25.
      Conclusions: The WA questions showed moderate reliability, while the WF
      instrument showed good reliability. Occupational health professionals can use the
      SDCs of the instruments to monitor changes in WA and WF in workers over time.

PMID- 29471534
TI  - Cypermethrin Promotes Lung Cancer Metastasis via Modulation of Macrophage
      Polarization by Targeting MicroRNA-155/Bcl6.
AB  - Cypermethrin (CYM), a type II pyrethroid, is widely used as an insecticide for
      agriculture and household. Cumulative evidence indicates that acute and chronic
      exposure to CYM might cause a number of health problems, such as cancer and
      neuronal system diseases. However, the molecular mechanism underlying this
      pathology is not known. The main objective of this study was to define the
      effects of CYM on macrophages and the implication of such effects in cancer
      metastasis and the potential mechanism involved. The effects of CYM on the
      macrophages were evaluated by detecting the expression of M1 and M2 macrophage
      polarization markers through ELISA, quantitative RT-PCR, and Western blot assay.
      Transwell and wound healing assays were used to test the migration of lung cancer
      cells after exposure to CYM in vitro and a metastasis animal model in vivo.
      Treatment with CYM significantly suppressed lipopolysaccharide (LPS)-induced M1
      macrophage polarization and promoted a shift toward M2 macrophage status.
      Mechanistically, CYM downregulated miR-155 significantly, leading to enhanced
      expression of its target gene Bcl6, thereby reducing the expression of mitogen
      activated protein kinase 4 (MKK4), an upstream kinase of c-Jun N-terminal kinases
      (JNK), and inhibiting JNK activation. Impaired JNK activation thus promoted a
      shift in macrophage polarization from the M1 to the M2 phenotype. Finally, CYM
      treated macrophages promoted metastasis of Lewis lung cancer cells in both in
      vitro and in vivo models. Taken together, our findings show that CYM is able to
      inhibit the M1 polarization and promote the macrophages to the M2 phenotype,
      which plays an important role in tumor metastasis.

PMID- 29471535
TI  - The MEDIA model: An innovative method for digitizing and training community
      members to facilitate an HIV prevention intervention.
AB  - As human immunodeficiency virus (HIV) continues to disproportionately affect
      African American women, practitioners remain committed to developing innovative
      strategies to reduce HIV prevalence. These strategies include training community
      organizations, such as churches, and utilizing digital media to make intervention
      dissemination more sustainable. This article describes one such effort to train
      lay community members within predominantly Black churches in Atlanta, GA, to
      implement an HIV prevention intervention. Lay educators were trained by
      translating a face-to-face Training of Facilitators (TOF) to a digital platform
      using the MEDIA (Motivate-Engage-Digitize-Implement-Assess) model. Formative
      evaluations, consultation with experts in the digital platform of choice, and the
      experience of two P4 for Women Master Trainers informed our translation. The
      model guided the translation process as our research team worked alongside
      topical experts and a production company to develop storyboards for core
      curriculum activities, which were later scripted and filmed with mock
      participants. A user guide, toolkit, and program website were also developed as
      supplemental materials to accompany the video training. Lessons learned from this
      study indicate future attempts at digitizing TOFs should keep in mind that
      digitization can be a time-consuming process, pilot testing in the new format is
      necessary even for a previously tested intervention, and the structure provided
      by facilitators in face-to-face training must be embedded into the format of
      digitized trainings.

PMID- 29471536
TI  - Variation Across Mitochondrial Gene Trees Provides Evidence for Systematic Error:
      How Much Gene Tree Variation Is Biological?
AB  - The use of large genomic data sets in phylogenetics has highlighted extensive
      topological variation across genes. Much of this discordance is assumed to result
      from biological processes. However, variation among gene trees can also be a
      consequence of systematic error driven by poor model fit, and the relative
      importance of biological vs. methodological factors in explaining gene tree
      variation is a major unresolved question. Using mitochondrial genomes to control
      for biological causes of gene tree variation, we estimate the extent of gene tree
      discordance driven by systematic error and employ posterior prediction to
      highlight the role of model fit in producing this discordance. We find that the
      amount of discordance among mitochondrial gene trees is similar to the amount of
      discordance found in other studies that assume only biological causes of
      variation. This similarity suggests that the role of systematic error in
      generating gene tree variation is underappreciated and critical evaluation of fit
      between assumed models and the data used for inference is important for the
      resolution of unresolved phylogenetic questions.

PMID- 29471538
TI  - Novel roles of ascorbate in plants: induction of cytosolic Ca2+ signals and
      efflux from cells via anion channels.
AB  - Ascorbate is not often considered as a signalling molecule in plants. This study
      demonstrates that, in Arabidopsis roots, exogenous l-ascorbic acid triggers a
      transient increase of the cytosolic free calcium activity ([Ca2+]cyt.) that is
      central to plant signalling. Exogenous copper and iron stimulate the ascorbate
      induced [Ca2+]cyt. elevation, while cation channel blockers, free radical
      scavengers, low extracellular [Ca2+], transition metal chelators, and removal of
      the cell wall inhibit this reaction. These data show that apoplastic redox-active
      transition metals are involved in the ascorbate-induced [Ca2+]cyt. elevation.
      Exogenous ascorbate also induces a moderate increase in programmed cell death
      symptoms in intact roots, but it does not activate Ca2+ influx currents in patch
      clamped root protoplasts. Intriguingly, the replacement of gluconate with
      ascorbate in the patch-clamp pipette reveals a large ascorbate efflux current,
      which shows sensitivity to the anion channel blocker, anthracene-9-carboxylic
      acid (A9C), indicative of the ascorbate release via anion channels. EPR
      spectroscopy measurements demonstrate that salinity (NaCl) triggers the
      accumulation of root apoplastic ascorbyl radicals in an A9C-dependent manner,
      confirming that l-ascorbate leaks through anion channels under depolarization.
      This mechanism may underlie ascorbate release, signalling phenomena, apoplastic
      redox reactions, iron acquisition, and control the ionic and electrical
      equilibrium (together with K+ efflux via GORK channels).

PMID- 29471537
TI  - The C-terminal helix of ribosomal P stalk recognizes a hydrophobic groove of
      elongation factor 2 in a novel fashion.
AB  - Archaea and eukaryotes have ribosomal P stalks composed of anchor protein P0 and
      aP1 homodimers (archaea) or P1*P2 heterodimers (eukaryotes). These P stalks
      recruit translational GTPases to the GTPase-associated center in ribosomes to
      provide energy during translation. The C-terminus of the P stalk is known to
      selectively recognize GTPases. Here we investigated the interaction between the P
      stalk and elongation factor 2 by determining the structures of Pyrococcus
      horikoshii EF-2 (PhoEF-2) in the Apo-form, GDP-form, GMPPCP-form (GTP-form), and
      GMPPCP-form bound with 11 C-terminal residues of P1 (P1C11). Helical structured
      P1C11 binds to a hydrophobic groove between domain G and subdomain G' of PhoEF-2,
      where is completely different from that of aEF-1alpha in terms of both position
      and sequence, implying that such interaction characteristic may be requested by
      how GTPases perform their functions on the ribosome. Combining PhoEF-2 P1-binding
      assays with a structural comparison of current PhoEF-2 structures and molecular
      dynamics model of a P1C11-bound GDP form, the conformational changes of the P1C11
      binding groove in each form suggest that in response to the translation process,
      the groove has three states: closed, open, and release for recruiting and
      releasing GTPases.

PMID- 29471539
TI  - Breaking Down Barriers to the Utilization of Standardized Tests and Outcome
      Measures in Acute Care Physical Therapist Practice: An Observational Longitudinal
      Study.
AB  - Background: Standardized tests and outcome measures (STOM) have not been
      consistently implemented as part of most physical therapists' practice. Incidence
      of STOM use among physical therapists at Beth Israel Deaconess Medical Center was
      similar to low levels cited nationally among acute care physical therapists.
      Targeted knowledge translation (KT) strategies have been suggested to promote the
      application of research evidence into clinical decision making. Purpose: The
      purpose of this quality improvement (QI) effort was to implement a series of
      interventions aimed at increasing both use and interpretation of STOM by physical
      therapists practicing in acute care. Design: This study used an observational
      longitudinal design. Methods: A literature review identified current barriers and
      facilitators to the use of STOM by physical therapists. KT strategies were
      tailored to the practice setting in order to target barriers and promote
      facilitators to the use of STOM. Data were collected through retrospective chart
      review at baseline and then subsequently at 4 periods following the
      implementation of the QI project. Results: A statistically significant increase
      in both the use (primary outcome) and interpretation (secondary outcome) of STOM
      was observed following the implementation of KT strategies. The increase was
      sustained at all subsequent measurement periods. Limitations: Limitations include
      the lack of a control group and the small number of setting- and diagnosis
      specific STOM available for use by physical therapists practicing in acute care.
      Conclusions: Implementation of KT strategies was associated with an increase in
      the frequency of use and interpretation of STOM. Similar QI efforts are feasible
      in any acute care physical therapy department and potentially other settings.

PMID- 29471540
TI  - Diagnosis and Microsurgical Ligation of an Intradural Ventral (Type IV)
      Arteriovenous Fistula of the Filum Terminale: 3-Dimensional Operative Video.

PMID- 29471541
TI  - The Caucasian Nasal Septum: An In Vivo Computed Tomography Study.
AB  - Background: The nasal septum is composed of cartilaginous and bony components and
      an understanding of each component volume is essential in both functional and
      cosmetic surgery. Objectives: We sought to radiographically measure septal
      dimensions on cross sectional computer tomography (CT) images, establishing
      average parameters for normal anatomy among a single, Caucasian population group.
      Methods: One hundred and fifty consecutive sinus CT scan images were examined and
      100 cases with appropriate sagittal views were included in the study. On each
      septum, the sagittal CT images were assessed and 14 points were identified and 23
      lengths measured and tabulated. Trigonometric formulae were used to accurately
      calculate surface areas of 11 resulting triangles which constituted the
      components of the nasal septum. Results: Measurements from 100 patients were
      included, with a mean age of 50.2 years, constituting 47 males and 53 females.
      Our surface area mapping established the following areas for both males and
      females respectively (mm2): quadrangular cartilage 1148 and 981; vomer 894 and
      741; perpendicular plate of ethmoid bone 1244 and 1006; and total surface area
      3287 and 2728. Our only statistically significant comparison in the series was
      found in the female series when age and reducing quadrilateral cartilage size
      were compared, highlighting reducing size with age (P = 0.04). Conclusions: The
      study presents the largest published data series representing nasal septal
      measurements on CT images in a living Caucasian population. Our data demonstrates
      that septal size remains constant after adolescence, throughout our age-varied
      series (18-79 years), except in the female population where the quadrilateral
      cartilage reduces in size with age. Level of Evidence 4: 

PMID- 29471543
TI  - Current and Future Potential Risk of Establishment of Grapholita molesta
      (Lepidoptera: Tortricidae) in Washington State.
AB  - The oriental fruit moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae),
      is a primary pest of stone fruits that cause significant economic damage. Larvae,
      which enter the host plant through shoot tips, damage shoots, and ripe fruits.
      Native to Asia, this pest now occurs in many fruit-growing countries, including
      the United States and Canada. Though the pest was previously reported from many
      states within the United States, its current distribution and the environmental
      variables that influence its distribution are not properly identified. The
      objectives of this study were to 1) identify the environmental factors associated
      with G. molesta current distribution, 2) predict the current distribution of G.
      molesta in Washington State (WA) using Maxent and Climex models, 3) identify
      those areas within WA best suited for establishment of pest free zones, areas of
      low pest prevalence, and pest free production areas, and 4) identify regions most
      at risk for further expansion of G. molesta populations as a function of climate
      change. The current models predicted a small portion of central WA is suitable to
      support G. molesta, which is consistent with observed distributions. However,
      climate change models predict that more areas will become suitable for the pest.
      These results indicate that action should be taken to monitor and reduce current
      populations of G. molesta to stem its potential expansion into the major
      commercial tree fruit production areas in the state.

PMID- 29471542
TI  - Specialized Pro-Resolving Lipid Mediators Regulate Ozone-Induced Pulmonary and
      Systemic Inflammation.
AB  - Exposure to ozone (O3) induces lung injury, pulmonary inflammation, and alters
      lipid metabolism. During tissue inflammation, specialized pro-resolving lipid
      mediators (SPMs) facilitate the resolution of inflammation. SPMs regulate the
      pulmonary immune response during infection and allergic asthma; however, the role
      of SPMs in O3-induced pulmonary injury and inflammation is unknown. We
      hypothesize that O3 exposure induces pulmonary inflammation by reducing SPMs. To
      evaluate this, male C57Bl/6J mice were exposed to filtered air (FA) or 1 ppm O3
      for 3 h and necropsied 24 h after exposure. Pulmonary injury/inflammation was
      determined by bronchoalveolar lavage (BAL) differentials, protein, and lung
      tissue cytokine expression. SPMs were quantified by liquid chromatography tandem
      mass spectrometry and SPM receptors leukotriene B4 receptor 1 (BLT-1), formyl
      peptide receptor 2 (ALX/FPR2), chemokine-like receptor 1 (ChemR23), and SPM
      generating enzyme (5-LOX and 12/15-LOX) expression were measured by real time
      PCR. 24 h post-O3 exposure, BAL PMNs and protein content were significantly
      increased compared to FA controls. O3-induced lung inflammation was associated
      with significant decreases in pulmonary SPM precursors (14-HDHA, 17-HDHA), the
      SPM PDX, and in pulmonary ALX/FPR2, ChemR23, and 12/15-LOX expression. Exogenous
      administration of 14-HDHA, 17-HDHA, and PDX 1 h prior to O3 exposure rescued
      pulmonary SPM precursors/SPMs, decreased proinflammatory cytokine and chemokine
      expression, and decreased BAL macrophages and PMNs. Taken together, these data
      indicate that O3-mediated SPM reductions may drive O3-induced pulmonary
      inflammation.

PMID- 29471544
TI  - 10 best resources on power in health policy and systems in low- and middle-income
      countries.
AB  - Power is a critical concept to understand and transform health policy and
      systems. Power manifests implicitly or explicitly at multiple levels-local,
      national and global-and is present at each actor interface, therefore shaping all
      actions, processes and outcomes. Analysing and engaging with power has important
      potential for improving our understanding of the underlying causes of inequity,
      and our ability to promote transparency, accountability and fairness. However,
      the study and analysis of the role of power in health policy and systems,
      particularly in the context of low- and middle-income countries, has been
      lacking. In order to facilitate greater engagement with the concept of power
      among researchers and practitioners in the health systems and policy realm, we
      share a broad overview of the concept of power, and list 10 excellent resources
      on power in health policy and systems in low- and middle-income countries,
      covering exemplary frameworks, commentaries and empirical work. We undertook a
      two-stage process to identify these resources. First, we conducted a
      collaborative exercise involving crowdsourcing and participatory validation,
      resulting in 24 proposed articles. Second, we conducted a structured literature
      review in four phases, resulting in 38 articles reviewed. We present the 10
      selected resources in the following categories to bring out key facets of the
      literature on power and health policy and systems-(1) Resources that provide an
      overarching conceptual exploration into how power shapes health policy and
      systems, and how to investigate it; and (2) examples of strong empirical work on
      power and health policy and systems research representing various levels of
      analyses, geographic regions and conceptual understandings of power. We conclude
      with a brief discussion of key gaps in the literature, and suggestions for
      additional methodological approaches to study power.

PMID- 29471545
TI  - High-protein distillers dried grains with solubles produced using a novel front
      end-back-end fractionation technology has greater nutritional value than
      conventional distillers dried grains with solubles when fed to growing pigs.
AB  - Two experiments were conducted to determine the standardized ileal digestibility
      (SID) of CP and AA, apparent total tract digestibility (ATTD) of GE, and DE and
      ME in conventional distillers dried grains with solubles (DDGS-CV) and in a novel
      source of high-protein distillers dried grains with solubles (DDGS-HP) produced
      by Lincolnway Energy (Nevada, IA). In Exp. 1, 18 barrows (initial BW: 72.47 +/-
      9.16 kg) that had a T-cannula installed in the distal ileum were allotted to a
      completely randomized design with 3 diets and 6 replicate pigs per diet. A
      nitrogen-free diet and 2 diets that contained cornstarch and DDGS-CV or DDGS
      HPLincolnway as the sole source of CP and AA were formulated. Diets were fed to
      pigs for 7 d, and ileal digesta were collected on days 6 and 7 of each period.
      The SID for Leu, Lys, Met, Phe, and Glu was greater (P < 0.05) in DDGS
      HPLincolnway than in DDGS-CV, and the SID of Ile, Val, and total indispensable
      AA, as well as the SID of Tyr, tended to be greater (P < 0.10) in DDGS
      HPLincolnway than in DDGS-CV. No difference between DDGS-CV and DDGS-HPLincolnway
      was observed for the SID of CP and all other AA. In Exp. 2, 24 barrows (initial
      BW: 52.80 +/- 2.55 kg) were housed individually in metabolism crates and randomly
      allotted to 1 of 3 diets. A corn-based basal diet (97.25% corn) and 2 diets that
      contained corn and DDGS-CV or corn and DDGS-HPLincolnway were formulated. Each
      diet was fed to 8 pigs. Feces and urine were collected using the marker to marker
      approach with 7-d adaptation and 5-d collection periods. The DE and ME in DDGS-CV
      and DDGS-HPLincolnway were calculated using the difference procedure. The DE and
      ME in DDGS-HPLincolnway on an as-fed basis were greater (P < 0.05) than in corn
      and DDGS-CV, but the ATTD of GE in DDGS-HPLincolnway and DDGS-CV was less (P <
      0.01) than in corn. In conclusion, the SID of some AA and the DE and ME in DDGS
      HPLincolnway were greater than in DDGS-CV.

PMID- 29471547
TI  - Erratum to "Comprehensive Intrametastatic Immune Quantification and Major Impact
      of Immunoscore on Survival".

PMID- 29471546
TI  - Longitudinal Analyses of Blood Transcriptome During Conversion to Psychosis.
AB  - The biological processes associated with the onset of schizophrenia remain
      largely unknown. Current hypotheses favor gene * environment interactions as
      supported by our recent report about DNA methylation changes during the onset of
      psychosis. Here, we conducted the first longitudinal transcriptomic analysis of
      blood samples from 31 at-risk individuals who later converted to psychosis and 63
      at-risk individuals who did not. Individuals were followed for a maximum of 1
      year. Blood samples were collected at baseline and at the end of follow-up and
      individuals served as their own controls. Differentially expressed genes between
      the 2 groups were identified using the RNA sequencing of an initial discovery
      subgroup (n = 15 individuals). The most promising results were replicated using
      high-throughput real-time qPCR in the whole cohort (n = 94 individuals). We
      identified longitudinal changes in 4 brain-expressed genes based on RNAseq
      analysis. One of these genes (CPT1A) was replicated in the whole cohort. The
      previously observed hypermethylation in NRP1 and GSTM5 during the onset of
      psychosis correlated with a decrease in corresponding gene expression. RNA
      sequencing also identified 2 co-expression networks that were impaired after
      conversion compared with baseline-the Wnt pathway including AKT1, CPT1A and
      semaphorins, and the Toll-like receptor pathway, related to innate immunity. This
      longitudinal study of transcriptomic changes in individuals with at-risk mental
      state revealed alterations during conversion to psychosis in pathways and genes
      relevant to schizophrenia. These results may be a first step toward better
      understanding psychosis onset. They may also help to identify new biomarkers and
      targets for disease-modifying therapeutic strategies.

PMID- 29471548
TI  - Maternal Smoking During Pregnancy and Negative Health Outcomes in the Offspring.

PMID- 29471549
TI  - Glutamate Dehydrogenase-Deficient Mice Display Schizophrenia-Like Behavioral
      Abnormalities and CA1-Specific Hippocampal Dysfunction.
AB  - Brain imaging has revealed that the CA1 subregion of the hippocampus is
      hyperactive in prodromal and diagnosed patients with schizophrenia (SCZ), and
      that glutamate is a driver of this hyperactivity. Strikingly, mice deficient in
      the glutamate synthetic enzyme glutaminase have CA1 hypoactivity and a SCZ
      resilience profile, implicating glutamate-metabolizing enzymes. To address this
      further, we examined mice with a brain-wide deficit in the glutamate-metabolizing
      enzyme glutamate dehydrogenase (GDH), encoded by Glud1, which should lead to
      glutamate excess due to reduced glutamate metabolism in astrocytes. We found that
      Glud1-deficient mice have behavioral abnormalities in the 3 SCZ symptom domains,
      with increased baseline and amphetamine-induced hyperlocomotion as a positive
      symptom proxy, nest building and social preference as a negative symptom proxy,
      and reversal/extradimensional set shifting in the water T-maze and contextual
      fear conditioning as a cognitive symptom proxy. Neuroimaging of cerebral blood
      volume revealed hippocampal hyperactivity in CA1, which was associated with
      volume reduction. Parameters of hippocampal synaptic function revealed excess
      glutamate release and an elevated excitatory/inhibitory balance in CA1. Finally,
      in a direct clinical correlation using imaging-guided microarray, we found a
      significant SCZ-associated postmortem reduction in GLUD1 expression in CA1. These
      findings advance GLUD1 deficiency as a driver of excess hippocampal excitatory
      transmission and SCZ symptoms, and identify GDH as a target for glutamate
      modulation pharmacotherapy for SCZ. More broadly, these findings point to the
      likely involvement of alterations in glutamate metabolism in the pathophysiology
      of SCZ.

PMID- 29471550
TI  - Phenotype-Genotype Correlation in Children with Neurofibromatosis Type 1.
AB  - Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder with an
      incidence of ~1 in 4,000 live births. Neurofibromin, the gene product, is
      ubiquitously expressed at high levels in the nervous system and functions as a
      tumor suppressor. Haploinsufficiency of neurofibromin through mutation leads to
      an increased risk of developing benign and malignant tumors in affected
      individuals. Although NF1 has complete penetrance, it displays considerable inter
      and intrafamilial variability in phenotypic expression which poses disease
      prediction and management problems. Some NF1 genotype-phenotype correlations have
      been described. To evaluate the genetic component of variable expressivity in
      NF1, we examined the phenotypic correlations between affected relatives in 52 NF1
      patients from 45 families.

PMID- 29471552
TI  - Novel GCH1 Compound Heterozygosity Mutation in Infancy-Onset Generalized
      Dystonia.

PMID- 29471551
TI  - Bilateral Striatal Necrosis after Sydenham's Chorea in a 7-Year-Old Boy: A 2-Year
      Follow-Up.
AB  - Child bilateral striatal necrosis (BSN) is a rare and etiologically heterogeneous
      condition. An association with group A streptococcus (GAS) infection was
      previously reported in two cases of BSN in infancy and early childhood. We here
      report on a 7-year-old boy who developed chorea and dystonia 20 days after
      symptomatic recovery from Sydenham's chorea. Repeated brain magnetic resonance
      imaging scans, obtained before, soon after the onset of the post-Sydenham
      symptoms, and 1 year later were consistent with an evolution from bilateral
      striatal microbleeding to necrosis, and consequently reduced basal ganglia volume
      and enlargement of the frontal horns. No support was found for other possible
      autoimmune, infectious, metabolic, toxic or genetic etiologies for BSN.
      Prednisone treatment was instituted and continued for 1 year. Two years after the
      onset of the post-Sydenham symptoms, the child, although much improved, still has
      generalized dystonic-choreic movements. This case confirms and extends into
      school age, the link between GAS and BSN.

PMID- 29471553
TI  - [The Role of Organizational Indicators within the Implementation of Cross
      Sectoral Mental Health Care and Home Treatment in Germany - A Literature and
      Theory Review].
AB  - OBJECTIVE: To elucidate organizational and human resource management-related
      drivers of community mental health services and home treatment in Germany.
      METHODS: Systematic review of psychiatric and organizational science literature,
      additional manual search. RESULTS: Relevant driver variables in community mental
      health services and home treatment have mostly been addressed. However, only a
      few have been evaluated and complex cause-and-effect models are missing so far.
      CONCLUSIONS: The proposed drivers, moderators, and throughputs should be
      integrated into an evaluation system that should be able to estimate effects of
      organizational and human resources on care-related and economic outcomes.

PMID- 29471554
TI  - [Day Surgery for Endoscopic Inguinal Hernia Repair].
AB  - BACKGROUND: Whereas international guidelines recommend day surgery for endoscopic
      inguinal hernia repair, this approach is still controversial in Germany. In the
      light of international guidelines and at the request of patients, we have
      established total extraperitoneal patch plastic (TEP) surgery in the outpatient
      setting in our hospital. METHODS: A retrospective analysis of all unilateral TEP
      procedures carried out between January 2013 and December 2015 in our outpatient
      surgery, focused on postoperative complications, conversion to admission and rate
      of recurrence. Patient satisfaction with the outpatient setting was evaluated by
      telephone interview. RESULTS: In the 3 year period analysed, 164 patients were
      admitted for day surgery. Outpatient surgery was carried out in 152 patients,
      whereas 12 patients had to be admitted overnight due to circulatory disturbance,
      pain or bleeding. A total of 102 patients could be questioned for follow-up.
      Hematoma developed in 9 patients, and recurrence of hernia in 3 patients.
      Infections or seromas were not described or detected. 88 patients were very
      satisfied with the outpatient procedure, and 82 patients would clearly prefer day
      surgery again. CONCLUSIONS: Unilateral endoscopic hernia repair is safe and can
      be performed in the outpatient setting without increased risk. Satisfaction and
      acceptance by the patients is high. There is a dramatic difference between day
      surgery and inpatient procedure in the costs for hernia repair and this is one of
      the major reasons why outpatient endoscopic hernia repair is still rare in
      Germany.

PMID- 29471555
TI  - [Pregnancy after Obesity and Metabolic Surgery - Risks and Complications].
AB  - The increasing prevalence of morbid obesity in Germany is associated with an
      increasing number of metabolic surgical interventions. Short-term surgical and
      long-term metabolic complications - such as nutrient deficiencies - are the main
      risks of metabolic surgery and the resulting malabsorption. Obesity, especially
      morbid obesity, is associated with a high incidence of female infertility. One
      important cause of female infertility in obese women is the polycystic ovary
      syndrome, with 6 - 10%. Metabolic surgery significantly increases the fertility
      of obese women. The positive effect of obesity surgery on weight loss, remission
      of comorbidities, psychological outcome and fertility (in comparison with the
      effect of conservative treatment) has led to an increase in the number of
      metabolic operations. Nutrient deficiencies after restrictive, combined and
      malabsorptive procedures must be considered. Prophylaxis of these deficiencies
      during pregnancy after obesity surgery must be based on intensive
      interdisciplinary treatment. The aim of this overview is to characterise the
      metabolic complications and their prophylaxis, which are specific for the various
      bariatric procedures and which, subsequently, require temporary or permanent
      surveillance and supplementation.

PMID- 29471556
TI  - ?

PMID- 29471557
TI  - Prospective Comparison of a Metal-Free Ceramic Total Knee Arthroplasty with an
      Identical Metal System.
AB  - AIMS: The aim of this open-label, prospective, short-term study was to carry out
      an initial comparison of a completely metal-free ceramic with a geometrically
      identical metallic arthroplasty over a 1-year follow-up period. METHODS: This
      study investigates a completely metal-free system using a composite matrix
      material containing aluminum oxide (Al2O3, BPK-S Integration, Peter Brehm GmbH,
      Weisendorf, Germany) or zirconium oxide (ZrO2, BPK-S Integration Ceramic, Biolox
      Delta-CeramTec GmbH, Plochingen, Germany). Eighty patients (40 in each group)
      received either a completely metal-free ceramic system (matrix of aluminum and
      zirconium oxide) or an anatomically identical metallic knee system made of a
      cobalt-chromium alloy. Clinical assessment was performed preoperatively, and
      during follow-up at 3 and 12 months, using the Knee Society Score, Oxford Knee
      Score, and EQ-5D-VAS. For radiological evaluation, standard preoperative and
      postoperative standardized radiographs were taken at the given follow-up visits.
      RESULTS: The postoperative clinical scores improved significantly at the 3- and
      12-month follow-ups, but did not differ statistically between the two groups. The
      radiologically evaluated mean postoperative mechanical and anatomical axes showed
      proper alignment within both groups at all times. No revision surgery had to be
      performed, and no complications or loosening were recorded whatsoever.
      CONCLUSIONS: To our knowledge, this is the first study comparing a total ceramic
      metal-free knee system with a geometrically identical metallic TKA (total knee
      arthroplasty). Longer follow-ups will be required to demonstrate the overall
      efficiency of this TKR and perhaps to expand its medical indication.

PMID- 29471558
TI  - Indication, Technique and Long-term Results after Shoulder Arthrodesis Performed
      with Plate Fixation.
AB  - AIM: Arthrodesis of the shoulder joint is a radical event, so it is difficult to
      explain its significance to patients. It has been the last resort in hopeless
      cases. Knowledge of long-term results and evaluation of advantages and
      disadvantages seems to be helpful in this regard. METHODS: Eleven patients with
      mean age of 45 (31 - 58) years were operated between 2000 and 2013. All patients
      could be included in the investigation (FU mean 8.5 [3 - 16] years; 8 male and 3
      female; right 9, left 2). Patients had the following indications: persistent
      instability 5 (2 with epilepsy), rotator cuff rupture 2 (1* after combined
      latissimus dorsi and teres major transfer), brachial plexus injury/defect 2,
      locked dislocation 1 and posttraumatic arthropathy 1. Fixation with DC plate (pre
      bent to 110 degrees ) was used in all cases; with special focus on placing at
      least one screw in the scapular neck. The targeted arthrodesis position was
      abduction 30 degrees , forward flexion 30 degrees , and internal rotation 30
      degrees . RESULTS: Active abduction improved from 12 to 63 degrees , forward
      flexion from 21 to 79 degrees  and internal rotation from 10 to 47 degrees  (mean
      values). In the resting position with hanging arm aside, mean abduction was 3
      degrees  and forward flexion 8 degrees . Nine of 11 patients had considerable
      relief of pain, from 8.3 to 2.4 points VAS. Five patients rated the outcome as
      excellent, 3 as good and 1 as satisfactory. Nine patients would repeat the
      procedure. In summary, an Oxford Shoulder Score of 31.6 points was achieved, and
      SSV of 58%. Bony fusion was achieved in all cases, 3 - 4 months p. o. in mean.
      There were no important neurological or angiological complications. CONCLUSIONS:
      Plate arthrodesis in the technique used achieves high fusion and a low
      complication rate. Relief of pain and functional improvement are astonishing.
      Analysis of our results indicates that correction of the positions mentioned
      above is necessary: i. o. arthrodesis position for abduction 25 degrees  (by
      means of pre-bending plate of 105 degrees ), forward flexion 20 degrees  and
      internal rotation 30 degrees  are suggested.

PMID- 29471559
TI  - [Suturing an Acute ACL Lesion with Dynamic Intraligamentary Stabilisation].
AB  - BACKGROUND: The established surgical technique for lesion of the anterior
      cruciate ligament (ACL) is reconstruction with an autologous tendon. However,
      patients after ACL-replacement have increased osteoarthritis rates. Possible
      explanations are persistent knee instability and the loss of the ACL's
      proprioceptive function. Therefore, surgeons have developed an alternative
      treatment to preserve the ACL by readapting femoral ACL lesions by temporary
      protective dynamic intraligamentary stabilisation (DIS). INDICATION: The
      indication includes acute (< 21 days old) ACL injuries of young patients who are
      active in sport. The rupture should be located in the proximal third of the ACL
      with a side-to-side interval of more than 5 mm in the antero-posterior tibial
      translation. METHODS: In this video, a 22-year-old patient with an ACL lesion was
      operated three weeks after injury. CONCLUSION: Readapting femoral ACL lesions by
      DIS is an adequate technique to preserve the ACL and to restore knee stability.

PMID- 29471560
TI  - ?
AB  - Bone sarcomas are extremely rare representing approximately 0.2% among all cancer
      types. Due to the rarity of these tumors both the patients and the physicians can
      overlook or misinterpret the first often unspecific symptoms of these tumors
      (pain, limping and swelling). Therefore, radiographic examination (X-ray and/or
      MRI) of the involved region in case of inexplicable symptoms is strongly
      recommended. The most common primary malignant bone tumor entity is osteosarcoma,
      followed by chondrosarcoma and Ewing sarcoma. Osteosarcomas and Ewing sarcomas
      occur predominantly in children, adolescents and young adults, while
      chondrosarcomas primarily affect older patients. Most of the tumors are located
      in the extremities and the pelvis and in about 90% of cases the surgical
      treatment can be performed by means of a limb-sparing wide resection. An
      endoprosthetic or biological reconstruction of the resulting defect, depending on
      several patient- und tumor-related factors, usually is necessary. Apart from the
      surgical treatment, patients with osteosarcoma and Ewing sarcoma require a pre-
      and postoperative chemotherapy, while Ewing sarcoma patients often undergo
      radiation therapy as well - in some cases as the only local therapy option.
      Regular follow-up examinations are required after the completion of treatment for
      the early detection and management of local and/or systemic recurrences.
      Diagnosis and therapy of these rare tumors must be obtained by an
      interdisciplinary approach for optimal patient care (i.e. oncologist,
      radiologists, pathologists, orthopaedic surgeons, radiotherapists). Without an
      interdisciplinary proceeding the risk of mistakes increases significantly, which
      can have grave consequences on the patients' prognosis and functional outcome.
      Therefore, the centralized treatment of these patients in specialized sarcoma
      centres is recommended.

PMID- 29471561
TI  - Nonalcoholic Fatty Liver Disease in Children.
AB  - Nonalcoholic steatohepatitis, a progressive form of nonalcoholic fatty liver
      disease (NAFLD), is one of the most common hepatic diseases in children who
      present with particular risk factors including obesity, sedentary lifestyle,
      and/or a predisposing genetic background. The worldwide prevalence of NAFLD in
      children is a worrying phenomenon because this disease is closely associated with
      the development of both cirrhosis and cardiometabolic syndrome in adulthood. To
      date, the etiopathogenesis of primary NAFLD in children is unknown. Understanding
      the pathogenetic mechanisms provides the basis to characterize early predictors
      of the disease and noninvasive diagnostic tools and to design novel specific
      treatments and possible management strategies. Despite a few clinical trials on
      the use of antioxidants combined with lifestyle intervention for NAFLD, no
      treatment exists for children with NAFLD. In this review, the authors provide an
      overview of current concepts in epidemiology, histological features,
      etiopathogenesis, diagnosis, and treatment of NAFLD in pediatric population.

PMID- 29471562
TI  - Can Elastography Differentiate Isolated Fatty Liver from Nonalcoholic
      Steatohepatitis?
AB  - Ultrasound and magnetic resonance (MR)-based elastography have demonstrated
      excellent performance for noninvasive staging of fibrosis in patients with
      nonalcoholic fatty liver disease (NAFLD); however, their ability to differentiate
      isolated fatty liver from nonalcoholic steatohepatitis (NASH) is unclear. In this
      review, the authors provide background on elastography and review the ability of
      elastography to discriminate between isolated steatosis and NASH. Studies with
      available data on the diagnosis of NASH histology are limited to vibration
      controlled transient elastography and MR elastography. A wide range of optimal
      cutoffs for the diagnosis of NASH are reported and likely depend on the
      prevalence of advanced fibrosis in the study population. MR elastography has good
      performance characteristics for identifying patients with any fibrosis who are at
      greatest risk of disease-related morbidity. Currently, neither modality can
      reliably discriminate NASH from simple steatosis. Novel multiparametric MR
      imaging and elastography are emerging and may help detect presence of NASH in the
      future.

PMID- 29471563
TI  - Hepatic Damage by Natural Remedies.
AB  - The rising burden of herbal and dietary supplement hepatotoxicity (HILI) is a
      growing concern in Western countries. The estimated incidence of HILI in well
      designed prospective studies ranges from less than 1 to 3 individuals per 100,000
      inhabitants/year. Herbal hepatotoxicity has a particular signature encompassing
      female predominance, hepatocellular type of damage with markedly elevated
      transaminases on presentation, more common unintentional rechallenge, and a
      greater risk of death/liver transplantation. Herbal hepatotoxicity recognition is
      particularly challenging for hepatologists because of the often hidden herbal
      consumption, difficulties in identifying the causative herbal component, and the
      possibility of contamination, adulteration, and misidentification, which preclude
      a proper adjudication and lead to inaccurate reporting of cases in scientific
      journals. Collaborative efforts to retrieve detailed phenotypic data and
      biological samples of patients with HILI would facilitate genomic and other
      molecular approaches for a better understanding of host risk factors and,
      hopefully, for biomarker identification.

PMID- 29471564
TI  - Genetic and Epigenetic Heterogeneity in Normal Liver Homeostasis and Its
      Implications for Liver Disease and Hepatocellular Cancer.
AB  - Hepatocellular carcinoma (HCC) is the most prevalent primary tumor of the liver,
      and is steadily becoming one of the most lethal cancers worldwide. Liver
      resection, which is the recommended procedure for early localized HCC, results in
      frequent recurrence (50-70%), while the standard of care for late-stage HCC,
      multikinase inhibitors, only improves survival by a few months. The lack of
      success for these treatment modalities is attributable, at least in part, to
      marked phenotypic heterogeneity within the tumor. Intratumoral heterogeneity
      (ITH) has emerged as a defining characteristic of human tumors, with individual
      cancer cells displaying distinct differences in properties including growth rate,
      metastatic capacity, and response to treatment. This heterogeneity, which is
      unlikely to be captured from a biopsy, impacts outcome because a single treatment
      targeting one cancer-specific pathway would spare tumor cells having distinct
      characteristics. Development of effective biomarkers remains a major challenge
      for similar reasons. Understanding, interpreting, and circumventing the impact of
      ITH is therefore paramount for developing reliable biomarkers and designing
      effective individualized treatment strategies for HCC.

PMID- 29471565
TI  - Fibrolamellar Carcinoma: Recent Advances and Unresolved Questions on the
      Molecular Mechanisms.
AB  - Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of primary liver
      cancer that affects adolescents and young adults without underlying liver
      disease. Surgery remains the mainstay of therapy; however, most patients are
      either not surgical candidates or suffer from recurrence. There is no approved
      systemic therapy and the overall survival remains poor. Historically classified
      as a subtype of hepatocellular carcinoma (HCC), FLC has a unique clinical,
      histological, and molecular presentation. At the genomic level, FLC contains a
      single 400kB deletion in chromosome 19, leading to a functional DNAJB1-PRKACA
      fusion protein. In this review, we detail the recent advances in our
      understanding of the molecular underpinnings of FLC and outline the current
      knowledge gaps.

PMID- 29471566
TI  - Mucosal-Associated Invariant T Cells in Chronic Inflammatory Liver Disease.
AB  - The broadening field of microbiome research has led to a substantial reappraisal
      of the gut-liver axis and its role in chronic liver disease. The liver is a
      central immunologic organ that is continuously exposed to food and microbial
      derived antigens from the gastrointestinal tract. Mucosal-associated invariant T
      (MAIT) cells are enriched in the human liver and can be activated by inflammatory
      cytokines and microbial antigens. In chronic inflammatory liver disease, MAIT
      cells are depleted suggesting an impaired MAIT cell-dependent protection against
      bacterial infections.

PMID- 29471567
TI  - Targeting Hepatitis D.
AB  - New therapeutic strategies to treat chronic hepatitis D are directed to deprive
      the hepatitis D virus (HDV) of functions necessary to complete its life cycle
      that are provided by the hepatitis B virus (HBV) and by the host. Current options
      are (1) the block by the synthetic peptide Myrcludex B of HBV surface antigen
      (HBsAg) entry into cells through the inhibition of the sodium taurocholate
      cotransporting receptor; (2) the inhibition with lonafarnib of the farnesylation
      of the large HD antigen, required for virion assembly; (3) the presumed reduction
      by the nucleic acid polymer REP 2139 of the release of the HBsAg and subviral HBV
      particles necessary for HD virion morphogenesis. Lonafarnib and Myrcludex in
      monotherapy reduced serum HDV-RNA but did not reduce the HBsAg and HD viremia
      rebounded after therapy; they may provide additional efficacy to pegylated
      interferon alpha (Peg IFN-alpha) therapy. Treatment with REP-2139 in combination
      with Peg IFN-alpha induced a sustained clearance both of the HDV-RNA and HBsAg in
      5 of 12 patients, providing the best interim results so far obtained in the
      therapy of chronic hepatitis D.

PMID- 29471569
TI  - Does Transjugular Intrahepatic Portosystemic Shunt Stent Differentially Improve
      Survival in a Subset of Cirrhotic Patients?
AB  - Does transjugular intrahepatic portosystemic shunt stent (TIPS) improve survival
      in a subgroup of patients? Yes. TIPS nearly halves portal pressure and increases
      the effective blood volume. In cases of acute variceal hemorrhage and with a high
      risk of treatment failure, defined as either hepatic venous pressure gradient
      higher than 20 mm Hg, Child B with active bleeding at the endoscopy, or Child C
      with less than 14 points, early or preemptive placement of TIPS (within 72 hours)
      improves survival. Also, in suitable patients with intractable or refractory
      ascites, TIPS improves survival if placed early in the course of treatment. While
      TIPS does not improve survival in other situations, it improves disease
      management, especially in patients without TIPS contraindications but with
      refractory bleeding, early rebleeding, portal vein thrombosis, and hepatorenal
      syndrome. Experience gained at the centers and follow-up of TIPS patients are key
      features that improve outcome. Important factors for selection and follow-up
      include cardiac function, inflammation, sarcopenia, age, and early evaluation for
      liver transplantation.

PMID- 29471568
TI  - The Receptor Interacting Protein Kinases in the Liver.
AB  - The receptor interacting serine/threonine kinase1 and 3 (RIPK1, RIPK3) are
      regulators of cell death and survival. RIPK1 kinase activity is required for
      necroptosis and apoptosis, while its scaffolding function is necessary for
      survival. Although both proteins can mediate apoptosis, RIPK1 and RIPK3 are most
      well-known for their role in the execution of necroptosis via the mixed lineage
      domain like pseudokinase. Necroptosis is a caspase-independent regulated cell
      death program which was first described in cultured cells with unknown
      physiologic relevance in the liver. Many recent reports have suggested that RIPK1
      and/or RIPK3 participate in liver disease pathogenesis and cell death. Notably,
      both proteins have been shown to mediate inflammation independent of cell death.
      Whether necroptosis occurs in hepatocytes, and how it is executed in the presence
      of an intact caspase machinery is controversial. In spite of this controversy, it
      is evident that RIPK1 and RIPK3 participate in many experimental liver disease
      models. Therefore, in addition to cell death signaling, their necroptosis
      independent role warrants further examination.

PMID- 29471570
TI  - [Differentiated Drug Therapy - Especially Important in Old Age].

PMID- 29471571
TI  - [57-Year-Old Women: Skin Alteration on Belly].

PMID- 29471572
TI  - [Cardiovascular Medication in Elderly Patients].
AB  - Elderly people show increased probability to develop atherosclerotic diseases; in
      consequence heart failure - most often following coronary heart disease - as well
      as atrial fibrillation is more common. Following guidelines may lead to
      polypharmacy, i. e. use of more than 5 drugs daily. Thus, drug interactions as
      well as side effects become more likely; especially in elderly patients reduced
      kidney function has to be taken into account. Only drugs which have shown to
      prolong life or to reduce symptoms in controlled clinical trials should be used.
      There is little evidence to use low dose aspirin or lipid lowering agents in
      primary prevention especially in elderly. ACE inhibitors, beta blocker and MRA
      are effective to improve symptoms and outcome in HFrEF but not in HFmEF or HFpEF.
      This also holds true for the elderly. Withdrawal of long term diuretic treatment
      in the elderly patients may lead to symptoms of heart failure or increase in
      blood pressure to hypertensive values often. In coronary heart disease beta
      blocker may be used to control symptoms as well as to reduce the need for
      coronary intervention following 1 year after myocardial infarction. Because the
      risk of stroke increases with age more than the risk of bleeding, the absolute
      benefit of oral anticoagulation in atrial fibrillation patients is highest in the
      elderly. NOAK appear to be safer and at least as efficacious as warfarin.

PMID- 29471573
TI  - [Which drugs in Hemato-Oncology are Unnecessary or Inappropriate for Use in the
      Elderly?]
AB  - There is a vast amount of drugs and therapeutic regimens available today to treat
      hemato-oncological diseases. This offers new opportunities to close known gaps of
      undertreatment in older individuals with cancer, but also increases the risk of
      overtreatment in this patient group. Currently available criteria (drug listings)
      for potentially inadequate prescribing in the elderly are not matured enough to
      serve hemato-oncologists as a guidance when trying to identify unnecessary or
      inappropriate cancer medication in routine clinical practice. In some clinical
      situations (e. g., decision-making for adjuvant treatment), online tools that
      allow for a rough prediction of remaining life expectancy (without or with
      cancer) as well as chemotherapy toxicity could help to detect risks of
      overtreatment in individual patients, however. Avoiding chemotherapy in distinct
      therapeutic situations has become possible for some hematological and solid
      tumors due to a growing number of novel targeted (i. e. non-cytostatic) drugs.
      This development appears of particular benefit for elderly patients. The present
      review discusses tools that generally could support the identification of
      overtreatment in older patients with such diseases. Drug examples are presented
      for some common hemato-oncological entities.

PMID- 29471574
TI  - [Type 2 Diabetes Diabetes in Older Adults: Example for Patient-Centered Drug
      Therapy].
AB  - Diabetes in older adults has a high prevalence and is frequently associated with
      comorbidities of the cardiovascular system, dysfunction of cognition as well as
      depression and impaired mobility or increased frailty. Furthermore, impaired
      renal function, heart failure, risk for hypoglycemia and polypharmacy has to be
      considered in the decision about the diabetes treatment strategy. The goal of
      blood glucose management is driven by patient relevant issues and patient self
      esteem, quality of life defined by the patient, preservation of physical and
      social mobility rather than potential long-term effects on reduction of cardio-
      and microvascular events in the future, which is limited by patient-inherent
      reduced life expectancy of the aged individual. Therefore, long-term diabetes
      medication should avoid hypoglycemia and prevent acute hyperglycemia or short
      term complications on morbidity and clinical course of geriatric syndromes
      associated with regular blood glucose levels above 200 mg/dl (11.1 mmol/l). The
      therapy should be safe, easy to handle for the patient and possibly affect co
      morbidities positively. However, there are limited data available about efficacy,
      safety and pharmacokinetics of drugs in patients over 75 years of age or older.
      Since more than 5 % of the population in Germany is older than 80 years means
      that more than 1 million of these individuals suffer from diabetes. It is time to
      ask for data in these elderly subpopulations by policy makers in health care.

PMID- 29471575
TI  - [Breast Cancer: Diagnostics and Therapy - the Most Important Facts for
      Internists].
AB  - LEARNING OBJECTIVES:  After reviewing this article, the participant should be
      able to: 1. Understand the epidemiology of breast cancer, its incidence and
      impact. 2. Appreciate the importance of early diagnosis and treatment. 3.
      Understand the concept of comprehensive breast cancer management and its
      multidisciplinarity. 4. Be knowledgeable about the entire process required to
      manage breast cancer, since the early diagnosis until the management of non
      breast related conditions derived from the treatment. 5. Position their specialty
      and knowledge in the process and know clearly their role and involvement in the
      management of the patients with breast cancer. SUMMARY:  Breast carcinoma
      accounts for the majority of the malignant diseases in women. In Germany has an
      estimated incidence of 70 000 new cases per year, which is 30 % of all the
      malignancies in women, predominantly between 45 and 83 years old, although it can
      affect as well younger women and men, the latter, in a very low rate. It is
      accountable for 17.4 % mortality in the country.The high frequency and impact of
      the mammary carcinoma had lead to the establishment and standardization of
      screening programs, encompassing self examination, early and regular
      consultation, sonography and mammography, aimed to the early detection not only
      of primary disease but also in recurrent or relapsing disease, and continued
      following up after treatment. Several treatment strategies and tools have been
      developed and are being chosen in accordance to the histology and biology of the
      tumor, the patient condition, the social and familiar status, with the increase
      of conservation of the mammary gland either by adjuvant or neoadjuvant therapies,
      with radiotherapy or by breast conserving surgery, improving therefore the
      quality of living without compromising the disease free survival. Next step in
      the process is the follow up, intended to maintain the patients the healthiest
      possible, not only from the malignancy but also minimizing the effects of the
      treatment strategies, incorporating lifestyle improving measures e.g. sports and
      nutrition, and alternative medicine resources like acupuncture, hence improving
      the disease free survival rate, the overall survival and diminishing the disease
      related impact yet personal, familiar, social and economical.The aim of this CME
      is to give a thorough review of this multifactorial entity, helping the
      healthcare professional understand the scientific aspects of it and, through
      comprehensive reading, provide a clear understanding of their role and degree of
      involvement in the breast cancer management process.

PMID- 29471576
TI  - [Vegetarian Diets in Children? - An Assessment from Pediatrics and Nutrition
      Science].
AB  - In Germany, the "Dietary Schedule for the 1st year of life" and the "Optimised
      Mixed Diet" for children and adolescents serve as scientifically based and
      generally applicable dietary concepts throughout the period of growth and
      development. Vegetarian diets as the lacto-ovo-vegetarian diet (exclusion of
      meat, fish) and the vegan diet (exclusion of all food groups of animal origin)
      need to be evaluated for their potential to safely meet the high and specific
      requirements for growth and development. In this regard, high-quality studies are
      needed. In individuals on lacto-ovo-vegetarian diets, the safe supply with
      critical nutrients should be checked by thorough dietary history, possibly
      additional laboratory tests in risk situations like pregnancy, infancy and
      toddlerhood. Children on pure vegan diet need ongoing elaborate dietary
      strategies and continuous supplementation at any age, similar to nutritional
      management in children with metabolic disorders. A vegan diet is disadvised
      during all periods with intense growth and development.

PMID- 29471577
TI  - [Advances in Cardiology - 40 Years Influenced by Erland Erdmann].

PMID- 29471578
TI  - 2017 Eberhard F. Mammen Award Announcements: Part II-Young Investigator Awards.

PMID- 29471579
TI  - Extrahemostatic Functions of Platelets and Coagulation Factors.

PMID- 29471580
TI  - Prevalence of early and late prematurity is similar among pediatric type 1
      diabetes patients and the general population.
AB  - BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) has increased in
      recent decades, as has the incidence of preterm births (<37 weeks). We aimed to
      evaluate and compare the prevalence of prematurity and early prematurity (<34
      weeks) and birth season variability among T1DM and non-T1DM children. METHODS: A
      nationwide cross-sectional study was conducted, with linkage of data from 13
      paediatric diabetes centers and Israeli National Registries, including T1DM
      patients and general non-T1DM population, born during 2000 to 2013. Gathered data
      included ethnicity, gender, birth week, weight, and season. The prevalence of
      prematurity and birth season were compared with the general population birth
      registry using Pearson Chi-square test. RESULTS: The study population included
      1452 T1DM patients, 52.7% males, and 2 138 668 subjects in the general non-T1DM
      population, 51.2% males. The prevalence of late and early prematurity was similar
      between groups (6.1% and 2.2% in the T1DM group vs 5.6% and 2.0% in the general
      non-T1DM group, P = 0.25 and P = 0.38, respectively). OR for prematurity among
      T1DM patients was 1.15 (0.95-1.39), P = 0.16. No difference in birth season was
      demonstrated between preterm and term, in T1DM and general non-T1DM populations.
      Ethiopian descent was more prevalent among T1DM patients compared with the non
      T1DM population, in both term and preterm born. CONCLUSIONS: This is the largest
      population-based study, and the first in the Middle East geographical area,
      indicating that prematurity, including early prematurity, is not associated with
      T1DM during childhood. The study was registered at https://clinicaltrials.gov/:
      NCT02929953.

PMID- 29471581
TI  - Brief Report: Association of Quantitative and Topographic Assessment of
      Heberden's Nodes With Knee Osteoarthritis: Data From the Osteoarthritis
      Initiative.
AB  - OBJECTIVE: To determine whether the presence, number, and topography (digit
      location and symmetry) of Heberden's nodes are associated with the incidence and
      progression of radiographic osteoarthritis (OA) of the knee. METHODS: We analyzed
      8,023 knees (with 8 years of follow-up) from the Osteoarthritis Initiative. Cox
      regression was performed on Heberden's node presence, total number, location, and
      symmetry (using 2 symmetry index models) obtained at baseline physical
      examination as well as self-report of Heberden's node presence for evaluation of
      association with radiographic knee OA incidence (development of a
      Kellgren/Lawrence grade of >=2) and progression (worsening in the medial joint
      space narrowing score of >=1). Covariate adjustments relevant to OA outcomes were
      performed. RESULTS: The presence of Heberden's nodes (in 64% of the subjects) at
      baseline physical examinations, but not subjective self-report of Heberden's
      nodes, was associated with radiographic knee OA incidence (hazard ratio [HR] 1.19
      and 95% confidence interval [95% CI] 1.001-1.402 [approached statistical
      significance]). Each additional Heberden's node found on physical examination was
      associated with knee OA incidence (HR 1.03 [95% CI 1.000-1.054] [approached
      statistical significance]) and progression (HR 1.04 [95% CI 1.016-1.063]). Knee
      OA incidence and progression were associated with Heberden's nodes located on the
      third digit (HR 1.26 [95% CI 1.068-1.487] and 1.18 [95% CI 1.019-1.361],
      respectively) and first digit (HR 1.186 [95% CI 0.992-1.418] [approached
      statistical significance] and HR 1.26 [95% CI 1.084-1.453], respectively).
      Heberden's node symmetry was associated with knee OA incidence (model 1 HR 1.09
      [95% CI 0.997-1.185] [approached statistical significance]) and progression
      (model 2 HR 1.13 [95% CI 1.035-1.234]). CONCLUSION: The number of Heberden's
      nodes, their locations, and symmetry were associated with knee OA incidence and
      progression over 8 years.

PMID- 29471582
TI  - Diabetic dyslipidaemia is associated with alterations in eNOS, caveolin-1, and
      endothelial dysfunction in streptozotocin treated rats.
AB  - BACKGROUND: Diabetes is a complex progressive disease characterized by chronic
      hyperglycaemia and dyslipidaemia associated with endothelial dysfunction.
      Oxidized LDL (Ox-LDL) is elevated in diabetes and may contribute to endothelial
      dysfunction. The aim of this study was to relate the serum levels of Ox-LDL with
      endothelial dysfunction in streptozotocin (STZ)-diabetic rats and to further
      explore the changes in endothelial nitric oxide synthase (eNOS) and caveolin-1
      (CAV-1) expression in primary aortic endothelial cells. METHODS: Diabetes was
      induced with a single intraperitoneal injection of STZ in male Wistar rats.
      During the hyperglycaemic diabetes state serum lipid markers, aortic relaxation
      and aortic endothelial cell eNOS and CAV-1 protein expressions were measured.
      RESULTS: Elevated serum Ox-LDL (STZ 1486 +/- 78.1 pg/mL vs control 732.6 +/-
      160.6 pg/mL, P < .05) was associated with hyperglycaemia (STZ 29 +/- 0.9 mmol/L
      vs control: 7.2 +/- 0.2 mmol/L, P < .001) and hypertriglyceridaemia (STZ 9.0 +/-
      1.5 mmol/L vs control: 3.0 +/- 0.3 mmol/L, P < .01) in diabetic rats. A
      significant reduction was observed in STZ-diabetic aortic endothelial cell eNOS
      and CAV-1 of 40% and 30%, respectively, accompanied by a compromised STZ-diabetic
      carbachol-induced vasodilation (STZ 29.6 +/- 9.3% vs control 77.2 +/- 2.5%, P <
      .001). CONCLUSIONS: The elevated serum Ox-LDL in hyperglycaemic STZ-diabetic rats
      may contribute to diabetic endothelial dysfunction, possibly through
      downregulation of endothelial CAV-1 and eNOS.

PMID- 29471583
TI  - National Partnership for Maternal Safety: Consensus Bundle on Safe Reduction of
      Primary Cesarean Births- Supporting Intended Vaginal Births.
AB  - Cesarean births and associated morbidity and mortality have reached near epidemic
      proportions. The National Partnership for Maternal Safety under the guidance of
      the Council on Patient Safety in Women's Health Care responded by developing a
      patient safety bundle to reduce the number of primary cesarean births. Safety
      bundles outline critical practices to implement in every maternity unit. This
      National Partnership for Maternity Safety bundle, as with other bundles, is
      organized into four domains: Readiness, Recognition and Prevention, Response, and
      Reporting and Systems Learning. Bundle components may be adapted to individual
      facilities, but standardization within an institution is advised. Evidence-based
      resources and recommendations are provided to assist implementation.

PMID- 29471584
TI  - Vasudhaiva Kutumbakam: The World Is One Family.

PMID- 29471585
TI  - Ripply3 is required for the maintenance of epithelial sheets in the morphogenesis
      of pharyngeal pouches.
AB  - During tissue development, the morphogenesis of epithelial sheets is regulated by
      many factors, including mechanical force, although the underlying mechanisms
      remain largely unknown. In the pharyngeal region of the vertebrate embryo,
      endodermal epithelium is reiteratively folded outward to form pharyngeal pouches,
      making partitions between the pharyngeal arches. Ripply3, encoding a member of
      the Ripply family of adaptor proteins, is required for the pouch formation
      posterior to the 2nd pharyngeal pouch. In this study, we found that the
      expression of mouse Ripply3 was specifically activated in accordance with the
      bending of the endodermal epithelium during the pouch formation. In Ripply3
      deficient embryos, a continuous monolayer of the endodermal epithelium was not
      maintained posterior to the 2nd pharyngeal pouch. Corresponding to the endodermal
      region of the deformed epithelium, the activated form of Integrin beta1, which
      was localized at the basal side of the epithelial cells in the wild-type embryos,
      was not persistently observed in the mutants. On the other hand, cell
      proliferation and apoptotic cell death in the endoderm were not obviously
      affected by the Ripply3 deficiency. Significantly, Ripply3 expressed in cultured
      cells was found to be preferentially accumulated in the focal adhesions, which
      are Integrin-mediated adhesive contact sites transmitting mechanical force
      between the extracellular matrix and attached cells. Furthermore, Ripply3
      promoted the maturation of focal adhesions in these cells. Thus, Ripply3 appears
      to have been activated to enhance the connection between the extracellular matrix
      and endodermal epithelial cells, as a mechanism to resist the mechanical stress
      generated during the bending of the epithelial sheets.

PMID- 29471586
TI  - Editorial: Inflammatory Back Pain and Axial Spondyloarthritis: Lessons for
      Clinical Practice and Epidemiologic Research.

PMID- 29471587
TI  - Managing unsolicited findings in genomics: A qualitative interview study with
      cancer patients.
AB  - OBJECTIVE: Next-generation sequencing (NGS) is increasingly being employed in the
      context of personalized cancer treatment. Anticipating unsolicited findings that
      may arise during a NGS procedure is a key consideration; however, little is known
      about cancer patients' intentions, needs, and preferences concerning the return
      of unsolicited findings. METHODS: A qualitative design using individual semi
      structured interviews with 24 cancer patients was utilized to explore patients'
      decisions on whether to receive unsolicited findings from NGS. These interviews
      were subsequently analyzed using the constant comparative method to develop codes
      and themes. RESULTS: We identified 4 interrelated themes that emerged in the
      context of the return of unsolicited findings. First, we describe how cancer
      patients expressed a strong need to control their lives. Second, we show the
      importance of family dynamics. Third, the NGS procedure regarding unsolicited
      findings is perceived as cognitively complex, and fourth, the procedure is also
      considered emotionally complex. CONCLUSIONS: The results of our study contribute
      to a better understanding of what cancer patients consider important and what may
      motivate and influence them when making decisions on the disclosure of
      unsolicited findings following NGS. We show how Joel Feinberg's classification of
      autonomy may help clinicians to better understand cancer patients' desire for
      autonomous decision making while also acknowledging the emotional and cognitive
      difficulties regarding the disclosure of unsolicited findings. These insights
      could be helpful for clinicians to guide patients through this complex process.

PMID- 29471588
TI  - Brief Report: Attenuated Effectiveness of Tumor Necrosis Factor Inhibitors for
      Anti-Human T Lymphotropic Virus Type I Antibody-Positive Rheumatoid Arthritis.
AB  - OBJECTIVE: To evaluate the effectiveness of tumor necrosis factor (TNF)
      inhibitors for the treatment of human T lymphotropic virus type I (HTLV-I)
      positive patients with rheumatoid arthritis (RA) in an area endemic for HTLV-I
      infection. METHODS: We conducted an observational study of 585 RA patients in
      whom TNF inhibitors were newly introduced as a first biologic disease-modifying
      antirheumatic drug in an area in southwestern Japan that is endemic for HTLV-I
      infection. RESULTS: Fifty patients (8.5%) were anti-HTLV-I antibody-positive. The
      ages of the patients in this group were significantly higher at entry compared
      with the ages of patients who were anti-HTLV-I antibody-negative (n = 535). The
      median Disease Activity Score in 28 joints using the erythrocyte sedimentation
      rate (DAS28-ESR) was 5.21. Among the total group of patients, 82% were anti
      citrullinated protein antibody (ACPA)-positive. The persistence rate of TNF
      inhibitors at 24 weeks was 89%. The median DAS28-ESR was significantly decreased
      at 24 weeks in each group. The European League Against Rheumatism (EULAR)
      response rate was significantly better in the anti-HTLV-I antibody-negative
      patients (P = 0.0277). Multiple regression analysis demonstrated that anti-HTLV-I
      antibody status was significantly associated with the EULAR response rate and
      change in the DAS28-ESR and was prominent especially in the ACPA-negative
      subjects. No patients developed adult T cell leukemia/lymphoma (ATL) or HTLV-I
      associated myelopathy (HAM) during the 24-week treatment period. CONCLUSION: The
      efficacy of TNF inhibitors may be attenuated in anti-HTLV-I antibody-positive
      patients with RA. ATL and HAM did not develop when TNF inhibitors were used for
      24 weeks, but the long-term risk is not known.

PMID- 29471589
TI  - Looking back and looking forward.

PMID- 29471590
TI  - Consumer use and response to online third-party raw DNA interpretation services.
AB  - BACKGROUND: With the availability of raw DNA generated from direct-to-consumer
      (DTC) testing companies, there has been a proliferation of third-party online
      services that are available to interpret the raw data for both genealogy and/or
      health purposes. This study examines the current landscape and downstream
      clinical implications of consumer use of third-party services. METHODS: Study
      participants were recruited online from social media platforms. A total of 321
      survey respondents reported using third-party services for raw DNA
      interpretation. RESULTS: Participants were highly motivated to explore raw DNA
      for ancestral information (67%), individual health implications (62%), or both
      (40%). Participants primarily used one of seven companies to interpret raw DNA;
      73% used more than one. Company choice was driven by the type of results offered
      (51%), price (45%), and online reviews (31%). Approximately 30% of participants
      shared results with a medical provider and 21% shared with more than one.
      Outcomes of sharing ranged from disinterest/discounting of the information to
      diagnosis of genetic conditions. Participants were highly satisfied with their
      decision to analyze raw DNA (M = 4.54/5), yet challenges in understanding
      interpretation results were reported irrespective of satisfaction ratings.
      CONCLUSION: Consumers face challenges in understanding the results and may seek
      out clinical assistance in interpreting their raw DNA results.

PMID- 29471592
TI  - Editorial: What Can Our Hands Tell Us About the Future of Our Knees?

PMID- 29471591
TI  - Improvement of life quality measured by Lansky Score after enzymatic replacement
      therapy in children with Gaucher disease type 1.
AB  - BACKGROUND: Gaucher disease type 1 (GD1, OMIM# 230800), is a condition with high
      impact in patient's quality of life (QoL). We report the improvement in QoL of
      children with GD1 measured by Lansky play-performance scale (LS) after enzymatic
      replacement therapy (ERT) and to describe our experience in the treatment of
      children with GD1. METHODS: Five children with diagnosis of GD1 received
      imiglucerase 60 mg/kg every two weeks. LS, hepatomegaly, splenomegaly,
      hemoglobin, platelets, and growth rate were measured every 6 months after
      beginning ERT for 30 months. RESULTS: After ERT, LS increased significantly from
      28 +/- 16.48 points before ERT to 70 +/- 10 (P = 0.0046) and 95 +/- 10 (P =
      0.0022) points after 6 and 30 months of ERT, respectively; hemoglobin and
      platelets changed significantly from 9.28 +/- 0.61 to 12.40 +/- 0.85 (P = 0.0198)
      and from 71.50 +/- 14.89 to 205.00 +/- 65.34 (P = 0.0428) after 30 months of ERT,
      respectively. All patients demonstrated decreased hepatic and splenic size with
      mean reductions of 66% and 80% at 30 months of treatment and the USG longitudinal
      axis was reduced in both liver and spleen after ERT. CONCLUSION: The use of ERT
      with imiglucerase 60 mg/kg every two weeks has substantial benefits and
      significantly improves QoL, assessed with Lansky Score, of the five children with
      GD1 studied.

PMID- 29471593
TI  - Clinical Evolution in Patients With New-Onset Inflammatory Back Pain: A
      Population-Based Cohort Study.
AB  - OBJECTIVE: Inflammatory back pain (IBP) is often an early manifestation of
      spondyloarthritis (SpA), but the prognosis of patients with incident IBP is
      unknown. This study was undertaken to investigate long-term outcomes in patients
      with IBP, and predictors of progression to SpA, in a population-based cohort.
      METHODS: We conducted a retrospective, longitudinal study using the Rochester
      Epidemiology Project, a longstanding population-based cohort of residents of
      Olmsted County, MN. Patients ages 16-35 years with clinical visits for back pain
      from 1999 to 2003 were identified, and we screened these patients for the
      presence of new-onset IBP and performed medical record reviews to collect data on
      clinical, laboratory, and imaging features of SpA. Outcomes in these patients
      were followed up until July 2016. We used survival analysis for competing risks
      to examine progression to either SpA, a non-SpA diagnosis, or resolution of back
      pain. Recursive partitioning was used to identify predictors of progression to
      SpA. RESULTS: Among 5,304 patients with back pain, we identified 124 patients
      with new-onset IBP. After a median follow-up of 13.2 years, IBP had progressed to
      SpA in 39 patients, 15 patients developed a non-SpA diagnosis, and 58 patients
      had resolution of IBP. At 10 years, the probability of having SpA was 30%, while
      the probability of resolution of IBP was 43%. The most important predictors for
      progression to SpA were uveitis, male sex, and family history of SpA. CONCLUSION:
      In a minority of patients, new-onset IBP progresses to SpA, while IBP resolves in
      many. That IBP often resolves may explain the difference between the prevalence
      of IBP (3-6%) and the prevalence of SpA (0.4-1.3%).

PMID- 29471594
TI  - Year in review 2017: Interstitial lung disease, pulmonary vascular disease and
      sleep.

PMID- 29471595
TI  - Procollagen-III peptide identifies adipose tissue-associated inflammation in type
      2 diabetes with or without nonalcoholic liver disease.
AB  - BACKGROUND: Procollagen-III peptide (PIIINP) is a marker of fibrosis associated
      with increased cardiometabolic risk and progression of chronic liver diseases
      such as nonalcoholic fatty liver disease (NAFLD) and steatohepatitis; its
      association with type 2 diabetes mellitus (T2DM) has not been elucidated yet. The
      aim of this study was to investigate the relationship among circulating PIIINP
      levels, metabolic traits, and body fat distribution in subjects with T2DM with or
      without NAFLD. METHODS: Data from 62 T2DM subjects recruited in our diabetes
      outpatient clinics at Sapienza University of Rome, Italy, were analysed.
      Participants underwent metabolic and inflammatory profiling (CRP, TNFalpha, IL-6,
      IL-8, WISP1, and adiponectin) and magnetic resonance imaging for diagnosing NAFLD
      on the basis of hepatic fat fraction (>=5.5%) and quantifying visceral and
      subcutaneous adipose tissue (AT) areas. Serum PIIINP was measured by human-PIIINP
      ELISA kits. RESULTS: Higher PIIINP levels correlated with greater BMI and
      visceral AT area and were associated with systemic signatures of AT-associated
      inflammation-ie, higher WISP-1, IL-8, and lower adiponectin levels; conversely,
      PIIINP did not differ significantly between T2DM patients with or without NAFLD
      and were not associated with hepatic fat fraction, Fatty Liver Index, FIB-4, or
      transaminases. CONCLUSIONS: Elevated circulating PIIINP levels specifically
      identify T2DM individuals with AT expansion and systemic proinflammatory profile
      suggestive for AT dysfunction; our results point toward a new role of PIIINP as a
      marker of fibroinflammation in dysmetabolic conditions, likely related to AT
      expansion.

PMID- 29471596
TI  - [Clinical Benefits of Transurethral Resection Under Narrow Band Imaging for Non
      Muscle Invasive Bladder Cancer].
AB  - The aim of this study was to reveal the clinical benefits of transurethral
      resection (TUR) under narrow band imaging (NBI-TUR) for non-muscle-invasive
      bladder cancer (NMIBC) compared with conventional white light imaging TUR (WLI
      TUR). The subjects were 172 patients with NMIBC who were followed for more than 1
      year after undergoing TUR with no additional postoperative treatment. In the WLI
      TUR group (n=101), lesions that were detected as positive after systematic
      intravesical observation under WLI were resected completely under WLI. In the NBI
      TUR group (n=71), similar observations under WLI were followed by systematic
      intravesical observation under NBI. After multiple site biopsy under NBI, TUR was
      performed for all lesions that were detected as positive under NBI. The
      sensitivity was calculated based on the results of cystoscopy and pathology of
      multiple site biopsy samples under WLI and NBI in the NBITUR group. The tumor
      recurrence rate was analyzed in both groups. Background factors did not differ
      significantly between the two groups, except for the observation period (63.3
      months in the WLI-TUR group vs 42.0 months in the NBI-TUR group, p<0.01). The
      procedure under NBI had significantly higher sensitivity (94.6% vs 75.0%, p<0.01)
      compared with that under WLI. The recurrence-free rate in the NBITUR group was
      significantly higher than that in the WLI-TUR group (p=0.013). The tumor
      recurrencefree rate of NBI-TUR is higher than that of conventional WLI-TUR for
      patients with NMIBC.

PMID- 29471597
TI  - [Clinical Study of 2014 ISUP New Grade Group Classification for Prostate Cancer
      Patients Treated by Androgen Deprivation Therapy].
AB  - The 2014 International Society of Urological Pathology (ISUP) has proposed a new
      grade group (GG) classification for Gleason scores (GS). The usefulness of the
      new GG classification was investigated with 518 prostate cancer patients who
      underwent androgen deprivation therapy. According to the new GG classification,
      Stages B-D and the new GG classification relapse-free rate for each stage were
      calculated using the Kaplan-Meier method. The new GG classification revealed a
      significant difference for the relapse-free rate only between some groups.
      Analysis using the Cox proportional hazards model indicated that the risk of
      relapse was higher in GGs 4 and 5 than in GG 1. The usefulness about the relapse
      free rate in androgen deprivation therapy of the 2014 ISUP new grade group
      classification a waits future examination.

PMID- 29471598
TI  - [Ureteral Cancer Developing in Retrocaval Ureter : A Case Report].
AB  - Ureteral cancer in the retrocaval ureter is rare. We herein report a patient with
      this condition laparoscopically treated. A 69-year-old man was referred to us
      because of right ureteral cancer diagnosed during ureteroscopic surgery for a
      ureteral calculus. Histological diagnosis of the ureteroscopically biopsied
      material was non-invasive papillary urothelial carcinoma, low grade (G2).
      Computed tomography (CT) demonstrated a retrocaval ureter : a double J stent
      placed during ureteroscopy assisted the diagnosis. The patient underwent
      retroperitoneoscopic complete nephroureterectomy on the right side. Sufficient
      separation of the right ureter and the inferior vena cava under
      retroperitoneoscopic procedures facilitated en bloc extirpation of the kidney and
      ureter with a minimal lower abdominal incision. The surgical procedures for
      ureteral cancer in the retrocaval ureter, should be preoperatively considered
      with care.

PMID- 29471599
TI  - [Acute Urinary Retention Caused by Acute Disseminated Encephalomyelitis : A Case
      Report].
AB  - An 11-year-old boy was referred to our department with the chief complaint of
      acute urinary retention. He had had a history of viral enteritis a few days
      before the onset of dysuria. He presented with a slight fever, mild headache and
      weakness of the extremities. A cerebrospinal fluid examination showed the
      elevation of cell number (cell number : 158/3, polynuclear cells : 29/3, and
      mononuclear cells : 129/3). Although spinal magnetic resonance imaging (MRI) did
      not show abnormal findings, fluid attenuated inversion recovery (FLAIR) image of
      the brain MRI showed a high signal area on the cerebral cortex. Acute
      disseminated encephalomyelitis (ADEM) was suspected from the clinical course, the
      cerebrospinal fluid examination, and brain MRI findings. A urethral catheter was
      indwelled for urinary retention, and steroid pulse therapy was promptly started.
      After removal of the urethral catheter seven days after the therapy initiation,
      normal urination without residual urine was observed. Findings of a cerebrospinal
      fluid test and brain MRI also showed improvement.

PMID- 29471600
TI  - [Two Cases of Transperineal Urethral Resection of the Prostate].
AB  - Two patients who could not take normal lithotomy position, one by fixation of the
      right hip joint due to coxitis, and the other by cerebral palsy, underwent
      transurethral resection of the prostate under perineal external urethrotomy. The
      perineal wound was closed and urethral catheter was inserted via the external
      urethral meatus. Postoperative course was uneventful for both patients.

PMID- 29471602
TI  - [Evolving Therapeutic Strategies in the Inflammatory Bowel Disease].
AB  - It is important to have effective therapeutic strategies and goals in clinical
      practice and research of inflammatory bowel disease. Conventional end points for
      clinical trials in Crohn's disease and ulcerative colitis have been based on
      composite indices, such as the Crohn's Disease Activity Index and the Mayo Clinic
      Score. Although these indices have been shown to reduce the intestinal injury to
      some extent, satisfactory results have not been obtained in improving the quality
      of life of patients. Recently, alternative measures of outcome and definitions of
      response are being developed beyond symptoms. Mucosal healing as a clinical
      response and treatment goal has showed better long-term outcomes. Patient
      reported outcomes (PROs) are emerging instrument directly created by patient to
      quantify symptoms. Coprimary realistic treatment 'target', comprising mucosal
      healing and PROs, can offer a clinically valid endpoint and can be readily
      applied in practice compare to existing composite indices. 'Treat-to-target'
      algorithm based on mucosal healing and PROs, in which therapy is progressively
      intensified until a specific personal treatment goal is reached, could improve
      quality of life of patient by reducing disease-related disability. Furthermore,
      histologic remission is an area of increased research focus and has the potential
      to guide treatment decisions in the future.

PMID- 29471601
TI  - [Bladder Rupture during Intravesical BCG Therapy : A Case Report].
AB  - A 69-year-old man received transurethral resection (TUR) ofbladder tumor. The
      histopathological diagnosis was urothelial carcinoma, high grade, pT1+pTis. The
      surgical specimens obtained by second TUR showed no residual malignancy
      histopathologically. Intravesical Bacillus Calmette-Guerin (BCG) instillation
      therapy was initiated 2 months after the second TUR. He complained of lower
      abdominal pain and painful urination on the day following the second instillation
      of BCG. Computed tomography and cystography demonstrated rupture ofthe urinary
      bladder. During 2 weeks ofconservative treatment, the symptoms persisted. Then,
      open repair ofthe bladder was performed. Intravesical BCG therapy has been a
      widely accepted treatment for bladder cancer with high grade Ta and T1, and
      carcinoma in situ. In the present case, thinning ofthe bladder wall, delayed
      wound healing caused by 2 TURs, and abdominal pressure may have been the factors
      leading to the bladder rupture in addition to inflammation of the bladder due to
      BCG instillation. Although bladder rupture caused by intravesical BCG therapy has
      not been reported, we must be aware ofthe possibility ofthis rare condition,
      especially after 2 consecutive TURs.

PMID- 29471603
TI  - [Monitoring Disease Activity: How and When?]
AB  - Inflammatory bowel disease (IBD) is a chronic, idiopathic inflammatory disease of
      gastrointestinal tract with waxing and waning clinical course, which may lead to
      irreversible bowel damage and a loss of bowel function. Cumulative intestinal
      damage results in complications such as stricture or fistulae, and eventually a
      large number of IBD patients undergo surgery. Notably, even during remission
      period (no clinical symptoms), subclinical inflammation often persists and the
      disease continues to progress. Therefore, the therapeutic target of IBD has been
      evolving from symptomatic control to mucosal healing to prevent structural
      intestinal damage. To achieve therapeutic goals in IBD, it is important to
      optimize therapy according to disease severity and response to treatment.
      Therefore, monitoring disease activity is recommended throughout the disease
      course of IBD. Especially strategies to monitor disease beyond symptoms through
      endoscopy, laboratory markers, and imaging is required.

PMID- 29471604
TI  - [How to Optimally Use Currently Available Drugs in a Therapeutic Algorithm?]
AB  - Recently, the incidence and prevalence of inflammatory bowel disease (IBD) have
      been increasing in worldwide, especially in Asian area. IBD is a chronic and
      progressive disease eventually causing bowel damage. The advance in the treatment
      of IBD over the past several decades has been achieved with the development of
      biologics. Furthermore, goals for management of IBD have been evolving from
      symptom-based management to mucosal healing, which can reduce the surgery rate
      and hospitalization. To treat the patients with IBD properly, identification of
      risk factors of patients should be preceded. In addition, the knowledge of
      several drugs, which are available in current situation is essential. In this
      review, optimal therapeutic approach with drugs including 5-aminosalicylate,
      steroid, immunomodulators and anti-TNF antagonists is discussed.

PMID- 29471605
TI  - [Emerging Therapies: What Are Promising in the Near Future?]
AB  - The treatment of inflammatory bowel disease has evolved with the development of
      anti-TNF agents. In spite of long-term effectiveness, many patients do not
      respond or no longer responds to these drugs. Therefore, the development of new
      drugs that act on different inflammatory pathways has become necessary.
      Vedolizumab, a gut-specific biological agent, inhibits interaction alpha4beta7
      integrin with mucosal addressin cell adhesion molecule-1 without inhibiting
      systemic immune responses. Long-term vedolizumab therapy in patients with Crohn's
      disease and ulcerative colitis was safe and effective. Additionally, vedolizumab
      can be used in patients already failed an anti-TNF therapy. Ustekinumab is a
      fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40
      subunit of IL-12 and IL-23. Ustekinumab will be a clinically effective agent to
      use in medically-refractory Crohn's disease especially as a second line drug.
      Tofacitinib is an oral, small molecule that inhibits JAK1, JAK3 and in a lesser
      extent, JAK2. Perhaps the most attractive things of these JAK inhibitors is that
      they are given orally instead of parenterally. Early results showed that patients
      with moderately to severely active ulcerative colitis receiving tofacitinib were
      more likely to achieve remission at 8 weeks than those receiving placebo.
      However, these results have not been as robust in Crohn's disease. Much of the
      positioning will depend on the safety profile such as opportunistic infection and
      atherogenic risk. The challenges for the future are to determine the therapeutic
      drug monitoring-guided dose optimization, optimal timing and drug combinations to
      produce the most effective, and safest outcomes for IBD patients.

PMID- 29471606
TI  - [Clinical Approach to Abdominal Pain as Functional Origin].
AB  - Abdominal pain is a common symptom that patients refer to a hospital. Organic
      causes should be differentiated in patients with abdominal pain and treatment
      should be administered in accordance with the causes. A meticulous history taking
      and physical examination are highly useful in making a diagnosis, and blood
      tests, imaging modalities, and endoscopy are useful for confirming diagnosis.
      However, in many cases, patients have functional disorders with no obvious
      abnormal findings obtained even if many diagnostic tests are performed. Patients
      with functional disorders usually complain the vague abdominal pain located in
      the center and other portions of the abdominal area. Although the most
      representative disease is irritable bowel syndrome, functional abdominal pain
      syndrome is currently researched as a new disease entity of functional abdominal
      pain. As various receptors related to functional abdominal pain have been
      discovered, drugs associated with those receptors are used to treat the
      disorders, and additional new drugs are vigorously developed. In addition,
      medical therapy with pharmacological or non-pharmacological psychiatric treatment
      is effective for treating functional abdominal pain.

PMID- 29471607
TI  - Mushroom Poisoning by Macrolepiota neomastoidea.
AB  - There are currently over 5,000-known species of mushrooms worldwide. Only 20-25%
      of mushrooms have been named, and 3% of these are poisonous. More than 95% of
      mushroom poisoning cases occur due to difficulties associated with the
      identification of mushroom species. Most of the fatal mushroom poisoning cases
      recorded to date have been related to the Amanita species. Until now, a case of
      fatal poisoning caused by Macrolepiota neomastoidea (M. neomastoidea) has not
      been reported in Asia. A 57-year-old male patient was admitted to the emergency
      room with nausea, vomiting, diarrhea, and abdominal pain. He reported ingesting
      wild mushrooms with his mother and sister about 2 days ago. His mother and sister
      were treated with only supportive care, but he was admitted to the intensive care
      unit and underwent liver transplantation due to acute liver failure. We are
      reporting a case of fatal M. neomastoidea intoxication from wild mushrooms, a
      rare case of mushroom poisoning.

PMID- 29471608
TI  - [Pancreatic Neuroendocrine Tumor Presenting as Acute Pancreatitis].
AB  - We report a case of acute pancreatitis secondary to pancreatic neuroendocrine
      tumor. A 46-year old man presented with upper abdominal pain. The serum amylase
      and lipase were elevated. Abdominal computed tomography (CT) and magnetic
      resonance cholangiopancreatography revealed a 1.7 cm sized mass at the pancreas
      body with a dilatation of the upstream pancreatic duct and mild infiltrations of
      peripancreatic fat. An endoscopic ultrasound-guided fine needle biopsy was
      performed for the pancreatic mass, but only necrotic tissue was observed on the
      pathologic examination. A chest and neck CT scan revealed anterior mediastinal,
      paratracheal, and cervical lymph node enlargement, which were indicative of
      metastasis. An ultrasound-guided core needle biopsy was performed for the
      enlarged neck lymph node, and pathologic examination revealed a metastatic poorly
      differentiated carcinoma. Immunohistochemical analysis showed positive staining
      for synaptophysin, chromogranin A, and CD 56, indicative of a neuroendocrine
      carcinoma.

PMID- 29471609
TI  - Comparison of surgical resection versus transarterial chemoembolization with
      additional radiation therapy in patients with hepatocellular carcinoma with
      portal vein invasion.

PMID- 29471610
TI  - Ototoxicity: A Challenge in Diagnosis and Treatment.
AB  - Ototoxicity is the pharmacological adverse reaction affecting the inner ear or
      auditory nerve, characterized by cochlear or vestibular dysfunction. The panorama
      of drug-induced hearing loss has widened over last few decades. Although ototoxic
      medications play an imperative role in modern medicine, they have the capacity to
      cause harm and lead to significant morbidity. Evidence has shown early detection
      of toxicity through prospective ototoxicity monitoring allows for consideration
      of treatment modifications to minimize or prevent permanent hearing loss and
      balance impairment. Although many ototoxicity monitoring protocols exist, their
      practicality is questionable due to several factors. Even though the existing
      protocols have proven to be effective, certain lacunae in practice have been
      encountered due to discrepancies among recommended protocols. Implementation of
      these protocols is mostly held back due to the incapacitated status of the
      patient. The choice of early ototoxicity identification techniques is still
      debatable due to variables such as high degree of sensitivity, specificity and
      reliability, less time consumption and less labour-intensive to the patient.
      Hence, the diagnosis and effective treatment of ototoxicity is challenging, even
      today. A stringent protocol with more practicality encompassing all elements
      aimed at profiling the effects of ototoxicity is greatly needed. This review
      describes an efficient application of ototoxicity monitoring and treatment
      protocol as an attempt to reduce the challenges in diagnosis and management of
      ototoxicity.

PMID- 29471611
TI  - Update on Bone-Conduction Auditory Brainstem Responses: A Review.
AB  - Auditory brainstem responses (ABR) have been used as a powerful and the most
      common objective tool to evaluate hearing sensitivity and to diagnose the types
      of hearing loss and neurological disorders, through the auditory peripheral
      pathway to a central level of the brainstem, since 1971. Although bone-conduction
      (BC) ABR could be an alternative to air-conduction (AC) ABR, as the former
      overcomes some limitations of the latter, the majority of clinicians rarely
      utilize it due to a lack of knowledge and no routine test administration. This
      review presents the weaknesses of AC ABR that apply to all clinical population,
      and discusses the development of BC ABR. The optimal placements of bone
      oscillators to obtain favorable clinical outcomes in infants, children, and
      adults, and the appropriate stimuli for BC ABR are examined. While providing
      absolute thresholds and latencies of BC ABR based on previous studies compared to
      AC ABR, this review includes clinical data of infants and young children with
      both normal hearing in terms of maturation, and with pathology such as congenital
      external auditory canal atresia. We recommend the future clinical application of
      BC ABR for candidacy as well as for patients with BC hearing implants.

PMID- 29471612
TI  - Analysis of Output Levels of an MP3 Player: Effects of Earphone Type, Music
      Genre, and Listening Duration.
AB  - Background and Objectives: To prevent noise induced hearing losses caused by
      listening to music with personal listening devices for young adults, this study
      was aimed to measure output levels of an MP3 and to identify preferred listening
      levels (PLLs) depending on earphone types, music genres, and listening durations.
      Subjects and METHODS: Twenty-two normal hearing young adults (mean=18.82,
      standard deviation=0.57) participated. Each participant was asked to select his
      or her most PLLs when listened to Korean ballade or dance music with an earbud or
      an over-the-ear earphone for 30 or 60 minutes. One side of earphone was connected
      to the participant's better ear and the other side was connected to a sound level
      meter via a 2 or 6 cc-couplers. Depending on earphone types, music genres, and
      listening durations, loudness A-weighted equivalent (LAeq) and loudness maximum
      time-weighted with A-frequency sound levels in dBA were measured. RESULTS:
      Neither main nor interaction effects of the PLLs among the three factors were
      significant. Overall output levels of earbuds were about 10-12 dBA greater than
      those of over-the-ear earphones. The PLLs were 1.73 dBA greater for earbuds than
      over-the-ear earphones. The average PLL for ballad was higher than for dance
      music. The PLLs at LAeq for both music genres were the greatest at 0.5 kHz
      followed by 1, 0.25, 2, 4, 0.125, 8 kHz in the order. Conclusions: The PLLs were
      not different significantly when listening to Korean ballad or dance music as
      functions of earphone types, music genres, and listening durations. However, over
      the-ear earphones seemed to be more suitable to prevent noise induce hearing loss
      when listening to music, showing lower PLLs, possibly due to isolation from the
      background noise by covering ears.

PMID- 29471613
TI  - Examination of Previously Published Data to Identify Patterns in the Social
      Representation of 'Hearing Aids' Across Countries.
AB  - BACKGROUND AND OBJECTIVES: Societal factors seem to exercise a strong influence
      on hearing aid uptake, use, and satisfaction. In particular, knowledge,
      perception, and attitude of people will have bearing towards their and others
      health behavior and decisions. The current study aimed at understanding the
      perception of hearing aids by adults belonging to the general population in
      different countries. SUBJECTS AND METHODS: The study employed a crosssectional
      design. A sample of 404 adults from India, Iran, Portugal, and the United Kingdom
      were recruited by relying on a convenience sampling. Previously published data
      was re-analyzed but it was applied for different approach. Free association task
      was used to collect the data. They were asked to provide up to five words or
      phrases that come to mind when thinking about "hearing aids." The data was
      initially analyzed based on qualitative content analysis. This was followed by
      quantitative cluster analysis and chi square analysis. RESULTS: The content
      analysis suggested 39 main categories of responses related to hearing aids. The
      cluster analysis resulted in five main clusters, namely: 1) positive attitude, 2)
      external factors, 3) hearing aid use and satisfaction, 4) etiology, and 5)
      benefits and limitations of technology. A few demographic factors (i.e.,
      education, occupation type, country) showed association with different clusters,
      although country of origin seemed to be associated with most clusters.
      CONCLUSIONS: The study provides us with unique insights into the perception of
      hearing aids by the general public, and additionally, the way demographic
      variables may influence these perceptions.

PMID- 29471614
TI  - Surgical steps for standard laparoscopic low anterior resection.
AB  - Once considered an incurable disease, the continuous evolution of technologies
      and techniques has improved both oncological outcomes and quality of life for
      patients with rectal cancer. Multiport laparoscopic surgery for rectal cancer is
      the standard of care in many institutions and countries and is the approach that
      has been most subjected to controlled trial. Following a number of randomized
      trials as well as large series and registry reports and several Cochrane reviews,
      there is no evidence of any oncological disadvantage to laparoscopic surgery
      compared with the open approach and there is good evidence of improved short-term
      outcomes and some evidence of improved long-term outcomes. We describe the
      "standard" approach to multiport, laparoscopic low anterior resection.

PMID- 29471615
TI  - Endoscopic ultrasound guided drainage of a pancreatic pseudocyst: a case report
      of a fistula to the common bile duct.

PMID- 29471616
TI  - Non-operative management of rectal cancer: future perspectives turning into
      reality?
AB  - The management of rectal cancer has considerably changed over the last decades
      and complete response to neoadjuvant chemoradiotherapy is becoming a common
      clinical entity. There is still no consensus on the definition of complete
      response to neoadjuvant treatment prior to surgery. Treatment programs are mostly
      heterogeneous and non-randomized. In addition, techniques to diagnose complete
      response are still unclear and there is no uniformity in surveillance modality of
      those patients managed without operative intervention. We review the most recent
      evidences reported in literature.

PMID- 29471617
TI  - How to reduce surgical complications in rectal cancer surgery using fluorescence
      techniques.
AB  - Anastomotic leakage (AL) is a serious complication in colorectal surgery leading
      to significant morbidity and mortality. Progressively lower anastomoses are
      associated with a greater leak rate. Adequate bowel perfusion has been stressed
      as one of the key elements for suture healing. Currently, there is no widespread
      method to assess and quantify the perfusion of gastrointestinal anastomoses
      intraoperatively, besides the subjective evaluation by the surgeon. The aim of
      this paper is to describe the basis of Indocyanine Green (ICG) fluorescence
      guided surgery applied to assessment of bowel perfusion and to highlight studies
      on the use of fluorescence angiography (FA) in laparoscopic rectal surgery. ICG
      fluorescence guided surgery has increasingly been used as a tool for
      intraoperative diagnostics to assess microperfusion and viability of tissues by
      means of a real-time FA; this technique has achieved the role of major
      contribution to intraoperative decision making during surgical procedures,
      especially in order to assess bowel perfusion before anastomosis creation in
      colorectal surgery. Several studies in literature already reported that ICG FA as
      a feasible technique to decrease AL rate in colorectal surgery; to date no
      randomized controlled trials have been completed but large series and prospective
      studies that focus on fluorescence perfusion assessment in rectal surgery have
      been published. Real time intraoperative ICG fluorescent angiography (FA) is a
      safe and feasible technique to guide the surgeon in intraoperative decision
      making process. ICG FA seems to reduce AL rates following rectal surgery for
      cancer. However large well-designed RCTs are needed to provide evidence for its
      routine use.

PMID- 29471619
TI  - Post-surgical recurrence of hepatocellular carcinoma along resection margin
      treated by percutaneous US-guided ablation.
AB  - BACKGROUND: The aim of this study was to evaluate the safety and efficacy of
      percutaneous ablation for hepatocellular carcinoma (HCC) hepatic recurrence along
      surgical resection margins to achieve complete cure or bridge for additional
      treatment. No current recommendations exist for these lesions. METHODS:
      Retrospective review of post-surgical recurrent HCC located along surgical
      margins treated by percutaneous ultrasound-guided ablation from 2006-2014.
      Ablation was performed by radiofrequency ablation (RFA) or percutaneous ethanol
      injection (PEI), selected for recurrence in proximity to extrahepatic organs.
      RESULTS: In total, nine patients (49-82 y, mean 73.8+/-8.3) were treated for 13
      recurrent HCC nodules (9-35 mm, mean 21.5+/-8.1) located along resection margins
      by RFA (11 nodules) and PEI (2 nodules). Mean time between surgery and
      percutaneous ablation was 64 months (range 10-149). At a mean follow-up of 17
      months (+/-9), complete ablation was achieved in 9 nodules (69.2%, 8 after RF, 1
      after PEI) and partial ablation was achieved in 4 nodules (3 after RFA, 1 after
      PEI). Complications were limited to minor abdominal pain in 2 patients requiring
      medical therapy (15.3%). Of the 4 partially ablated nodules, subsequent therapy
      achieved complete response in 3 nodules (1 patient with TACE, 1 patient with
      stereotactic radiotherapy, and one with liver transplantation), while the last
      nodule progressed despite subsequent TACE. CONCLUSIONS: HCC recurrence along the
      surgical margin can be safely and effectively treated by percutaneous therapy,
      despite the misconception of the surgical margin as a hostile location.
      Percutaneous treatment may bridge the patient for additional therapy.

PMID- 29471618
TI  - Visual probing of rectal neoplasia: near-infrared interrogation of primary tumors
      and secondary lymph nodes.
AB  - Laparoscopic and endoscopic colorectal intervention and operations have their
      basis in real-time, image-based decision-making and step-by-step sequenced
      technical progress. The capacity to visualize accurately malignant disease
      wherever it may be including within the primary lesion and its draining lymph
      node basin as well as at potential sites of metastatic harbor (i.e. peritoneum,
      liver and lung) would allow more accurate surgery at the time of operation and
      enable personalized, stratified surgical intervention. In addition, such capacity
      could efficiently compress the diagnostic and therapeutic stages of a patient's
      progress from presentation, through work-up and onto appropriate treatment,
      important in this era of restricted resource and increased user demand. Near
      infrared endolaparoscopic illumination enables broad spectral imaging of tissue
      in situ, most often, at present, in conjunction with the approved safe and low
      cost fluorophore indocyanine green. While additional targeted agents are in
      development, here we detail how this developed and available technology may be
      used as a visual probe of neoplasia to inform surgeons regarding functional,
      tissue characterization through the direct observation of metabolic and
      metabolomic processes within the area under inspection perhaps helping in the
      distinction between invasive cancer and non-invasive dysplastic lesions. This
      understanding can inform and accelerate development of specific agents and
      techniques that can better advance surgical practice into the era of surgical
      data science and true precision surgery.

PMID- 29471620
TI  - Augmented reality for breast imaging.
AB  - Augmented reality (AR) enables the superimposition of virtual reality
      reconstructions onto clinical images of a real patient, in real time. This allows
      visualization of internal structures through overlying tissues, thereby providing
      a virtual transparency vision of surgical anatomy. AR has been applied to
      neurosurgery, which utilizes a relatively fixed space, frames, and bony
      references; the application of AR facilitates the relationship between virtual
      and real data. Augmented breast imaging (ABI) is described. Breast MRI studies
      for breast implant patients with seroma were performed using a Siemens 3T system
      with a body coil and a four-channel bilateral phased-array breast coil as the
      transmitter and receiver, respectively. Gadolinium was injected as a contrast
      agent (0.1 mmol/kg at 2 mL/s) using a programmable power injector. Dicom
      formatted images data from 10 MRI cases of breast implant seroma and 10 MRI cases
      with T1-2 N0 M0 breast cancer, were imported and transformed into augmented
      reality images. ABI demonstrated stereoscopic depth perception, focal point
      convergence, 3D cursor use, and joystick fly-through. ABI can improve clinical
      outcomes, providing an enhanced view of the structures to work on. It should be
      further studied to determine its utility in clinical practice.

PMID- 29471621
TI  - Oncoplastic breast reduction in conservative surgery.
AB  - Advances in reconstructive breast surgery with new materials and techniques now
      allow us to offer patients the best possible cosmetic results without the risks
      associated with oncological control of the disease. These advances, in both
      oncological and plastic surgery, have led to a new field, oncoplastic breast
      surgery, which enables us to undertake large resections and, with advance
      planning, and prevent subsequent deformities. This is particularly important when
      more than 30% of the breast volume is removed, as it allows us to obtain precise
      information for conservative surgery according to the site of the lesion and to
      set the boundary between conservative surgery and mastectomy.

PMID- 29471622
TI  - Effectiveness of influenza vaccine in preventing medically-attended influenza
      virus infection in primary care, Israel, influenza seasons 2014/15 and 2015/16.
AB  - IntroductionInfluenza vaccine is recommended for the entire population in Israel.
      We assessed influenza vaccine effectiveness (VE) for the 2014/15 and 2015/16
      seasons in Israel, for the first time. Methods: Combined nose and throat swab
      specimens were collected from patients with influenza-like illness (ILI)
      presenting to sentinel primary care clinics and tested for influenza virus by RT
      PCR. VE of the trivalent inactivated vaccine (TIV) was assessed using test
      negative case-control design. Results: During the 2014/15 season 1,142 samples
      were collected; 327 (28.6%) were positive for influenza, 83.8% A(H3N2), 5.8%
      A(H1N1)pdm09, 9.2% B and 1.2% A un-subtyped. Adjusted VE against all influenza
      viruses for this influenza season was -4.8% (95% confidence interval (CI): -54.8
      to 29.0) and against influenza A(H3N2), it was -15.8% (95% CI: -72.8 to 22.4).
      For the 2015/16 season, 1,919 samples were collected; 853 (44.4%) were positive
      for influenza, 43.5% A(H1N1)pdm09, 57% B, 0.7% A(H3N2) and 11 samples positive
      for both A(H1N1)pdm09 and B. Adjusted VE against all influenza viruses for this
      influenza season was 8.8% (95% CI: -25.1 to 33.5), against influenza
      A(H1N1)pdm09, it was 32.3% (95% CI: (-4.3 to 56.1) and against influenza B, it
      was -2.2% (95% CI: (-47.0 to 29.0). Conclusions: Using samples from patients with
      ILI visiting sentinel clinics in Israel, we demonstrated the feasibility of
      influenza VE estimation in Israel.

PMID- 29471623
TI  - Monitoring human enteric viruses in wastewater and relevance to infections
      encountered in the clinical setting: a one-year experiment in central France,
      2014 to 2015.
AB  - BackgroundHuman enteric viruses are resistant in the environment and transmitted
      via the faecal-oral route. Viral shedding in wastewater gives the opportunity to
      track emerging pathogens and study the epidemiology of enteric infectious
      diseases in the community. Aim: The aim of this study was to monitor the
      circulation of enteric viruses in the population of the Clermont-Ferrand area
      (France) by analysis of urban wastewaters. Methods: Raw and treated wastewaters
      were collected between October 2014 and October 2015 and concentrated by a two
      step protocol using tangential flow ultrafiltration and polyethylene glycol
      precipitation. Processed samples were analysed for molecular detection of
      adenovirus, norovirus, rotavirus, parechovirus, enterovirus (EV), hepatitis A
      (HAV) and E (HEV) viruses. Results: All wastewater samples (n = 54) contained
      viruses. On average, six and four virus species were detected in, respectively,
      raw and treated wastewater samples. EV-positive samples were tested for EV-D68 to
      assess its circulation in the community. EV-D68 was detected in seven of 27 raw
      samples. We collected data from clinical cases of EV-D68 (n = 17), HAV (n = 4)
      and HEV infection (n = 16) and compared wastewater-derived sequences with
      clinical sequences. We showed the silent circulation of EV-D68 in September 2015,
      the wide circulation of HAV despite few notifications of acute disease and the
      presence in wastewater of the major HEV subtypes involved in clinical local
      cases. Conclusion: The environmental surveillance overcomes the sampling bias
      intrinsic to the study of infections associated with hospitalisation and allows
      the detection in real time of viral sequences genetically close to those reported
      in clinical specimens.

PMID- 29471625
TI  - Erratum for Euro Surveill. 2018;23(6).

PMID- 29471626
TI  - Job vacancy at the European Centre for Disease Prevention and Control.

PMID- 29471627
TI  - Oxidant-Free C(sp2)-H Functionalization/C-O Bond Formation: A Kolbe Oxidative
      Cyclization Process.
AB  - An anodic oxidation/cyclization of 2-arylbenzoic acids for the synthesis of
      dibenzopyranones has been developed. The reaction proceeds at room temperature
      with no oxidant or electrolyte required and exhibits a high atom economy with H2
      being the only byproduct. A series of dibenzopyranones was obtained in good to
      excellent yields. Urolithins A, B, and C are formally synthesized by adopting
      this method as a key step to demonstrate its synthetic utility.

PMID- 29471624
TI  - Interim effectiveness of trivalent influenza vaccine in a season dominated by
      lineage mismatched influenza B, northern Spain, 2017/18.
AB  - The 2017/18 interim estimate of trivalent influenza vaccine effectiveness (VE)
      was 39% (95% confidence interval: 20-54) in Navarre. Compared with individuals
      unvaccinated in the current and five previous seasons, VE against influenza B was
      41% for current and any prior doses, 67% for current vaccination only, and 22%
      for any prior doses, and 43%, 51% and 54%, respectively against influenza
      A(H3N2). This suggests moderate VE despite predominance of lineage mismatched
      influenza B.

PMID- 29471629
TI  - Biocompatible Microporous Organically Modified Silicate Material with Rapid
      Internal Diffusion of Protons.
AB  - A new four-component organically modified silicate (ORMOSIL) material was
      developed with optical pH sensors in mind. Through a sol-gel process, the
      porosity of an ORMOSIL framework was optimized to allow rapid diffusion of
      protons, ideal for fast response to pH in an optical sensor. The optically
      transparent material was produced by catalyzing the dual polymerization of 3
      (glycidoxy)propyltrimethoxysilane (GPTMS) and propyltriethoxysilane (PrTES) with
      boron trifluoride diethyl etherate. The performance of the resulting material in
      fluorescence based optical pH sensors was evaluated by incorporation of active
      dye components in the inorganic polymer framework. It is demonstrated that the
      material has a short response time ( t90 < 30 s) and high stability in medium and
      during storage, and resulting sensor spots are biocompatible. It is concluded
      that this ORMOSIL material has excellent properties for optical pH sensors.

PMID- 29471628
TI  - Activation of Pyruvate Dehydrogenase by Sodium Dichloroacetate Shifts Metabolic
      Consumption from Amino Acids to Glucose in IPEC-J2 Cells and Intestinal Bacteria
      in Pigs.
AB  - The extensive metabolism of amino acids (AA) as fuel is an important reason for
      the low use efficiency of protein in pigs. In this study, we investigated whether
      regulation of the pyruvate dehydrogenase kinase (PDK)/pyruvate dehydrogenase
      alpha 1 (PDHA1) pathway affected AA consumption by porcine intestinal epithelial
      (IPEC-J2) cells and intestinal bacteria in pigs. The effects of knockdown of
      PDHA1 and PDK1 with small interfering RNA (siRNA) on nutrient consumption by IPEC
      J2 cells were evaluated. IPEC-J2 cells were then cultured with sodium
      dichloroacetate (DCA) to quantify AA and glucose consumption and nutrient
      oxidative metabolism. The results showed that knockdown of PDHA1 using siRNA
      decreased glucose consumption but increased total AA (TAA) and glutamate (Glu)
      consumption by IPEC-J2 cells ( P < 0.05). Opposite effects were observed using
      siRNA targeting PDK1 ( P < 0.05). Additionally, culturing IPEC-J2 cells in the
      presence of 5 mM DCA markedly increased the phosphorylation of PDHA1 and PDH
      phosphatase 1, but inhibited PDK1 phosphorylation ( P < 0.05). DCA treatment also
      reduced TAA and Glu consumption and increased glucose depletion ( P < 0.05).
      These results indicated that PDH was the regulatory target for shifting from AA
      metabolism to glucose metabolism and that culturing cells with DCA decreased the
      consumption of AAs by increasing the depletion of glucose through PDH activation.

PMID- 29471633
TI  - Benchmarks and Breakthroughs.

PMID- 29471630
TI  - Ir(III)/MPAA-Catalyzed Mild and Selective C-H Amidation of N-Sulfonyl Ketimines:
      Access To Benzosultam-Fused Quinazolines/Quinazolinones.
AB  - Ir(III)-catalyzed unprecedented mild C-H amidation for weakly coordinating cyclic
      N-sulfonyl ketimines, accelerated by a mono protected l-amino acid, has been
      developed. The method uses 1,4,2-dioxazol-5-ones as the robust amidating reagent
      in conjunction with a catalytic amount of silver triflate. It is highly selective
      and does not require a stoichiometric amount of oxidants or additives. A series
      of mechanistic experiments was performed to gain some insights into the reaction
      mechanism. The strategy provides easy access to novel benzosultam-quinazoline and
      benzosultam-quinazolinone hybrid scaffolds endowed with pharmaceutically relevant
      features.

PMID- 29471634
TI  - Force fields for monovalent and divalent metal cations in TIP3P water based on
      thermodynamic and kinetic properties.
AB  - Metal cations are essential in many vital processes. In order to capture the role
      of different cations in all-atom molecular dynamics simulations of biological
      processes, an accurate parametrization is crucial. Here, we develop force field
      parameters for the metal cations Li+, Na+, K+, Cs+, Mg2+, Ca2+, Sr2+, and Ba2+ in
      combination with the TIP3P water model that is frequently used in biomolecular
      simulations. In progressing toward improved force fields, the approach presented
      here is an extension of previous efforts and allows us to simultaneously
      reproduce thermodynamic and kinetic properties of aqueous solutions. We
      systematically derive the parameters of the 12-6 Lennard-Jones potential which
      accurately reproduces the experimental solvation free energy, the activity
      derivative, and the characteristics of water exchange from the first hydration
      shell of the metal cations. In order to reproduce all experimental properties, a
      modification of the Lorentz-Berthelot combination rule is required for Mg2+.
      Using a balanced set of solution properties, the optimized force field parameters
      aim to capture the fine differences between distinct metal cations including
      specific ion binding affinities and the kinetics of cation binding to
      biologically important anionic groups.

PMID- 29471635
TI  - Global potential energy surface of ground state singlet spin O4.
AB  - A new global potential energy for the singlet spin state O4 system is reported
      using CASPT2/aug-cc-pVTZ ab initio calculations. The geometries for the six
      dimensional surface are constructed using a novel point generation scheme that
      employs randomly generated configurations based on the beta distribution. The
      advantage of this scheme is apparent in the reduction of the number of required
      geometries for a reasonably accurate potential energy surface (PES) and the
      consequent decrease in the overall computational effort. The reported surface
      matches well with the recently published singlet surface by Paukku et al. [J.
      Chem. Phys. 147, 034301 (2017)]. In addition to the O4 PES, the ground state N4
      PES is also constructed using the point generation scheme and compared with the
      existing PES [Y. Paukku et al., J. Chem. Phys. 139, 044309 (2013)]. The singlet
      surface is constructed with the aim of studying high energy O2-O2 collisions and
      predicting collision induced dissociation cross section to be used in simulating
      non-equilibrium aerothermodynamic flows.

PMID- 29471636
TI  - Semiclassical analysis of jm -> j'm' transitions in rotationally inelastic
      collisions in cell experiments.
AB  - Recent quantum calculations of rotationally inelastic collisions of NaK
      (A1Sigma+) with He or Ar in a cell experiment are analyzed using semiclassical
      approximations valid for large quantum numbers. The results suggest a physical
      interpretation of jm -> j'm' transitions based on the vector model and lead to
      expressions that explicitly involve the initial and final polar angles of the
      angular momentum of the target molecule. The relation between the polar angle
      theta and the azimuthal quantum number m links the semiclassical results for the
      change in polar angle (theta -> theta') to quantum results for an m -> m'
      transition. Analytic formulas are derived that relate the location and width of
      peaks in the final polar angle distribution (PAD) to the K-dependence of the
      coefficients dK(j, j'), which are proportional to tensor cross sections sigmaK(j 
      > j'). Several special cases are treated that lead to final PADs that are
      approximately Lorentzian or sinc functions centered at theta' = theta. Another
      interesting case, "angular momentum reversal," was observed in the calculations
      for He. This phenomenon, which involves a reversal of the direction of the
      target's angular momentum, is shown to be associated with oscillatory behavior of
      the dK for certain transitions. Finally, several strategies for obtaining the dK
      coefficients from experimental data are discussed.

PMID- 29471637
TI  - Adsorption of squaraine molecules to Au(111) and Ag(001) surfaces.
AB  - The adsorption of anilino squaraines, an important chromophore for the use in
      organic solar cells, to Ag(001) and Au(111) has been studied with scanning
      tunneling microscopy. Self-assembly into square building blocks with eight
      molecules per unit cell is revealed on the Ag surface, while no ordering effects
      occur on gold. The squaraine-silver interaction is mediated by the carbonyl and
      hydroxyl oxygens located in the center of the molecule. The intermolecular
      coupling, on the other hand, is governed by hydrogen bonds formed between the
      terminal isobutyl groups and oxygen species of adjacent molecules. The latter
      gets maximized by rotating the molecules by a few degrees against a perfect
      square alignment. A similar molecular pattern does not form on Au(111) due to
      symmetry mismatch. Moreover, the high electronegativity of gold reduces the
      directing effect of oxygen-metal bonds that trigger the ordering process on
      silver. As a consequence, only frustrated three-fold symmetric units that do not
      expand into an ordered molecular network are present on the gold surface.

PMID- 29471638
TI  - Monitoring polariton dynamics in the LHCII photosynthetic antenna in a
      microcavity by two-photon coincidence counting.
AB  - The relaxation dynamics of light-harvesting complex II in an optical cavity is
      explored theoretically by multidimensional photon coincidence counting
      spectroscopy. This technique reveals the dynamics in both single (e) and double
      (f) excitation bands. We study how the polariton dynamics are affected by
      coupling to photon modes and molecular vibrations described by a realistic
      spectral density at 77 K. Without the cavity, the e- and f-band energy transfer
      pathways are not clearly resolved due to the line broadening caused by fast
      exciton dephasing. The strong coupling to cavity photons results in well-resolved
      polariton modes. The hybrid nature of polaritons slows down their energy transfer
      rates.

PMID- 29471639
TI  - Using monomer vibrational wavefunctions to compute numerically exact (12D)
      rovibrational levels of water dimer.
AB  - We compute numerically exact rovibrational levels of water dimer, with 12
      vibrational coordinates, on the accurate CCpol-8sf ab initio flexible monomer
      potential energy surface [C. Leforestier et al., J. Chem. Phys. 137, 014305
      (2012)]. It does not have a sum-of-products or multimode form and therefore
      quadrature in some form must be used. To do the calculation, it is necessary to
      use an efficient basis set and to develop computational tools, for evaluating the
      matrix-vector products required to calculate the spectrum, that obviate the need
      to store the potential on a 12D quadrature grid. The basis functions we use are
      products of monomer vibrational wavefunctions and standard rigid-monomer basis
      functions (which involve products of three Wigner functions). Potential matrix
      vector products are evaluated using the F matrix idea previously used to compute
      rovibrational levels of 5-atom and 6-atom molecules. When the coupling between
      inter- and intra-monomer coordinates is weak, this crude adiabatic type basis is
      efficient (only a few monomer vibrational wavefunctions are necessary), although
      the calculation of matrix elements is straightforward. It is much easier to use
      than an adiabatic basis. The product structure of the basis is compatible with
      the product structure of the kinetic energy operator and this facilitates
      computation of matrix-vector products. Compared with the results obtained using a
      [6 + 6]D adiabatic approach, we find good agreement for the inter-molecular
      levels and larger differences for the intra-molecular water bend levels.

PMID- 29471640
TI  - Temperature dependence of dissociative electron attachment to bromo-chlorotoluene
      isomers: Competition between detachment of Cl- and Br.
AB  - Dissociative electron attachment to three isomers of bromo-chlorotoluene was
      investigated in the electron energy range from 0 to 2 eV for gas temperatures in
      the range of 392-520 K using a crossed electron-molecular beam apparatus with a
      temperature regulated effusive molecular beam source. For all three molecules,
      both Cl- and Br- are formed. The ion yields of both halogenides show a pronounced
      temperature effect. In the case of Cl- and Br-, the influence of the gas
      temperature can be observed at the threshold peak close to 0 eV. The population
      of molecules that have some of their out-of-plane modes excited varies strongly
      in the temperature range investigated, indicating that such vibrations might play
      a role in the energy transfer towards bond breaking. Potential energy curves for
      the abstraction of Cl- and Br- were calculated and extrapolated into the
      metastable domain. The barriers in the diabatic curves approximated in this way
      agree well with the ones derived from the temperature dependence observed in the
      experiments.

PMID- 29471641
TI  - Origin of the size-dependence of the equilibrium van der Waals binding between
      nanostructures.
AB  - Nanostructures can be bound together at equilibrium by the van der Waals (vdW)
      effect, a small but ubiquitous many-body attraction that presents challenges to
      density functional theory. How does the binding energy depend upon the size or
      number of atoms in one of a pair of identical nanostructures? To answer this
      question, we treat each nanostructure as a whole object, not as a collection of
      atoms. Our calculations start from an accurate static dipole polarizability for
      each considered nanostructure, and an accurate equilibrium center-to-center
      distance for the pair (the latter from experiment or from the vdW-DF-cx
      functional). We consider the competition in each term -C2k/d2k (k = 3, 4, 5) of
      the long-range vdW series for the interaction energy, between the size dependence
      of the vdW coefficient C2k and that of the 2kth power of the center-to-center
      distance d. The damping of these vdW terms can be negligible, but in any case, it
      does not affect the size dependence for a given term in the absence of non-vdW
      binding. To our surprise, the vdW energy can be size-independent for quasi
      spherical nanoclusters bound to one another by vdW interaction, even with strong
      nonadditivity of the vdW coefficient, as demonstrated for fullerenes. We also
      show that, for low-dimensional systems, the vdW interaction yields the strongest
      size-dependence, in stark contrast to that of fullerenes. We illustrate this with
      parallel planar polycyclic aromatic hydrocarbons. The size dependences of other
      morphologies or bonding types lie between, as shown by sodium clusters.

PMID- 29471642
TI  - Linear and non-linear infrared response of one-dimensional vibrational Holstein
      polarons in the anti-adiabatic limit: Optical and acoustical phonon models.
AB  - The theory of linear and non-linear infrared response of vibrational Holstein
      polarons in one-dimensional lattices is presented in order to identify the
      spectral signatures of self-trapping phenomena. Using a canonical transformation,
      the optical response is computed from the small polaron point of view which is
      valid in the anti-adiabatic limit. Two types of phonon baths are considered:
      optical phonons and acoustical phonons, and simple expressions are derived for
      the infrared response. It is shown that for the case of optical phonons, the
      linear response can directly probe the polaron density of states. The model is
      used to interpret the experimental spectrum of crystalline acetanilide in the C=O
      range. For the case of acoustical phonons, it is shown that two bound states can
      be observed in the two-dimensional infrared spectrum at low temperature. At high
      temperature, analysis of the time-dependence of the two-dimensional infrared
      spectrum indicates that bath mediated correlations slow down spectral diffusion.
      The model is used to interpret the experimental linear-spectroscopy of model
      alpha-helix and beta-sheet polypeptides. This work shows that the Davydov
      Hamiltonian cannot explain the observations in the NH stretching range.

PMID- 29471643
TI  - Optimization of long range potential interaction parameters in ion mobility
      spectrometry.
AB  - The problem of optimizing Lennard-Jones (L-J) potential parameters to perform
      collision cross section (CCS) calculations in ion mobility spectrometry has been
      undertaken. The experimental CCS of 16 small organic molecules containing carbon,
      hydrogen, oxygen, nitrogen, and fluoride in N2 was compared to numerical
      calculations using Density Functional Theory (DFT). CCS calculations were
      performed using the momentum transfer algorithm IMoS and a 4-6-12 potential
      without incorporating the ion-quadrupole potential. A ceteris paribus
      optimization method was used to optimize the intercept sigma and potential well
      depth epsilon for the given atoms. This method yields important information that
      otherwise would remain concealed. Results show that the optimized L-J parameters
      are not necessarily unique with intercept and well-depth following an exponential
      relation at an existing line of minimums. Similarly, the method shows that some
      molecules containing atoms of interest may be ill-conditioned candidates to
      perform optimizations of the L-J parameters. The final calculated CCSs for the
      chosen parameters differ 1% on average from their experimental counterparts. This
      result conveys the notion that DFT calculations can indeed be used as potential
      candidates for CCS calculations and that effects, such as the ion-quadrupole
      potential or diffuse scattering, can be embedded into the L-J parameters without
      loss of accuracy but with a large increase in computational efficiency.

PMID- 29471644
TI  - Magnetic moment and magnetic anisotropy of Ge3Mn5 thinfilms on Ge(111) substrate:
      A density functional study.
AB  - Magnetism and magnetic anisotropy energy (MAE) of the Ge3Mn5 bulk, free-standing
      surface, and Ge3Mn5(001)|Ge(111) thinfilms and superlattice have been
      systemically investigated by using the relativistic first-principles electronic
      structure calculations. For Ge3Mn5 adlayers on Ge(111) substrates within Mn1
      termination, the direction of magnetization undergoes a transition from in-plane
      at 1 monolayer (ML) thickness (MAE = -0.50 meV/ML) to out-of-plane beginning at 3
      ML thickness (nearly invariant MAE = 0.16 meV/ML). The surficial/interfacial MAE
      is extracted to be 1.23/-0.54 meV for Mn1-termination; the corresponding value is
      0.19/1.03 meV for Mn2/Ge-termination; the interior MAE is averaged to be 0.09 meV
      per ML. For various Ge3Mn5 systems, the in-plane lattice expansion and/or
      interlayer distance contraction would enhance the out-of-plane MAE. Our
      theoretical magnetic moments and MAEs fit well with the experimental
      measurements. Finally, the origination of MAE is elucidated under the framework
      of second-order perturbation with the electronic structure analyses.

PMID- 29471645
TI  - Erratum: "Combining the ensemble and Franck-Condon approaches for calculating
      spectral shapes of molecules in solution" [J. Chem. Phys. 148, 024110 (2018)].

PMID- 29471646
TI  - Computing energy levels of CH4, CHD3, CH3D, and CH3F with a direct product basis
      and coordinates based on the methyl subsystem.
AB  - Quantum mechanical calculations of ro-vibrational energies of CH4, CHD3, CH3D,
      and CH3F were made with two different numerical approaches. Both use
      polyspherical coordinates. The computed energy levels agree, confirming the
      accuracy of the methods. In the first approach, for all the molecules, the
      coordinates are defined using three Radau vectors for the CH3 subsystem and a
      Jacobi vector between the remaining atom and the centre of mass of CH3. Euler
      angles specifying the orientation of a frame attached to CH3 with respect to a
      frame attached to the Jacobi vector are used as vibrational coordinates. A direct
      product potential-optimized discrete variable vibrational basis is used to build
      a Hamiltonian matrix. Ro-vibrational energies are computed using a re-started
      Arnoldi eigensolver. In the second approach, the coordinates are the spherical
      coordinates associated with four Radau vectors or three Radau vectors and a
      Jacobi vector, and the frame is an Eckart frame. Vibrational basis functions are
      products of contracted stretch and bend functions, and eigenvalues are computed
      with the Lanczos algorithm. For CH4, CHD3, and CH3D, we report the first J > 0
      energy levels computed on the Wang-Carrington potential energy surface [X.-G.
      Wang and T. Carrington, J. Chem. Phys. 141(15), 154106 (2014)]. For CH3F, the
      potential energy surface of Zhao et al. [J. Chem. Phys. 144, 204302 (2016)] was
      used. All the results are in good agreement with experimental data.

PMID- 29471647
TI  - The hydrophilic-to-hydrophobic transition in glassy silica is driven by the
      atomic topology of its surface.
AB  - The surface reactivity and hydrophilicity of silicate materials are key
      properties for various industrial applications. However, the structural origin of
      their affinity for water remains unclear. Here, based on reactive molecular
      dynamics simulations of a series of artificial glassy silica surfaces annealed at
      various temperatures and subsequently exposed to water, we show that silica
      exhibits a hydrophilic-to-hydrophobic transition driven by its silanol surface
      density. By applying topological constraint theory, we show that the surface
      reactivity and hydrophilic/hydrophobic character of silica are controlled by the
      atomic topology of its surface. This suggests that novel silicate materials with
      tailored reactivity and hydrophilicity could be developed through the topological
      nanoengineering of their surface.

PMID- 29471648
TI  - Erratum: "Towards numerically robust multireference theories: The driven
      similarity renormalization group truncated to one- and two-body operators" [J.
      Chem. Phys. 144, 164114 (2016)].

PMID- 29471649
TI  - Low-energy electron collisions with proline and pyrrolidine: A comparative study.
AB  - We present a comparative study on the calculated cross sections obtained for the
      elastic collisions of low-energy electrons with the amino acid proline (C5H9NO2)
      and its building block pyrrolidine (C4H9N). We employed the Schwinger
      multichannel method implemented with pseudopotentials to compute integral,
      differential, and momentum transfer cross sections in the static-exchange plus
      polarization approximation, for energies up to 15 eV. We report three shape
      resonances for proline at around 1.7 eV, 6.8 eV, and 10 eV and two shape
      resonances for pyrrolidine centered at 7 eV and 10.2 eV. The present resonance
      energies are compared with available experimental data on vertical attachment
      energies and dissociative electron attachment, where a good agreement is found.
      From the comparison of the present results with available calculated cross
      sections for the simplest carboxylic acid, formic acid (HCOOH), and from
      electronic structure calculations, we found that the first resonance of proline,
      at 1.7 eV, is due the presence of the carboxylic group, whereas the other two
      structures, at 6.8 eV and 10 eV, clearly arise from the pyrrolidine ring. A
      comparison between the differential cross sections for proline and pyrrolidine at
      some selected energies of the incident electron is also reported in this paper.

PMID- 29471650
TI  - Electronic annealing Fermi operator expansion for DFT calculations on metallic
      systems.
AB  - Density Functional Theory (DFT) calculations with computational effort which
      increases linearly with the number of atoms (linear-scaling DFT) have been
      successfully developed for insulators, taking advantage of the exponential decay
      of the one-particle density matrix. For metallic systems, the density matrix is
      also expected to decay exponentially at finite electronic temperature and linear
      scaling DFT methods should be possible by taking advantage of this decay. Here we
      present a method for DFT calculations at finite electronic temperature for
      metallic systems which is effectively linear-scaling (O(N)). Our method generates
      the elements of the one-particle density matrix and also finds the required
      chemical potential and electronic entropy using polynomial expansions. A fixed
      expansion length is always employed to generate the density matrix, without any
      loss in accuracy by the application of a high electronic temperature followed by
      successive steps of temperature reduction until the desired (low) temperature
      density matrix is obtained. We have implemented this method in the ONETEP linear
      scaling (for insulators) DFT code which employs local orbitals that are optimised
      in situ. By making use of the sparse matrix machinery of ONETEP, our method
      exploits the sparsity of Hamiltonian and density matrices to perform calculations
      on metallic systems with computational cost that increases asymptotically
      linearly with the number of atoms. We demonstrate the linear-scaling
      computational cost of our method with calculation times on palladium
      nanoparticles with up to ~13 000 atoms.

PMID- 29471651
TI  - Composite pulses in N-level systems with SU(2) symmetry and their geometrical
      representation on the Majorana sphere.
AB  - High fidelity and robustness in population inversion is very desirable for many
      quantum control applications. We expand composite pulse schemes developed for two
      level dynamics and present an analytic solution for the coherent evolution of an
      N-level quantum system with SU(2) symmetry, for achieving high fidelity and
      robust population inversion. Our approach offers a platform for accurate steering
      of the population transfer in physical multi-level systems, which is crucial for
      fidelity in quantum computation and achieving fundamental excitations in nuclear
      magnetic resonances and atomic physics. We also introduce and discuss the
      geometrical trajectories of these dynamics on the Majorana sphere as an
      interpretation, allowing us to gain physical insight on the dynamics of many-body
      or high-dimensional quantum systems.

PMID- 29471652
TI  - Formation and identification of borane radical anions isolated in solid argon.
AB  - The infrared (IR) spectrum of borane(3) anions (BH3-) isolated in solid Ar was
      recorded; two vibrational modes were observed at 2259.4 and 606.6 cm-1, which
      were assigned to the BH2 stretching (nu3) and out-of-plane large-amplitude (nu2)
      modes, respectively. These anions were produced by the electron bombardment of an
      Ar matrix sample containing a small proportion of B2H6 and H2 during matrix
      deposition or by the photolysis of single-bridged-B2H5- in an Ar matrix with the
      selected ultraviolet light. The band positions, relative intensity ratios,
      isotopic splitting pattern, and isotopic shift ratios of the observed IR features
      of BH3- are generally in good agreement with those predicted by the B2PLYP/aug-cc
      pVTZ method.

PMID- 29471654
TI  - Erratum: "Driven similarity renormalization group: Third-order multireference
      perturbation theory" [J. Chem. Phys. 146, 124132 (2017)].

PMID- 29471653
TI  - Quantifying entanglement of rotor chains using basis truncation: Application to
      dipolar endofullerene peapods.
AB  - We propose a variational approach for the calculation of the quantum entanglement
      entropy of assemblies of rotating dipolar molecules. A basis truncation scheme
      based on the total angular momentum quantum number is proposed. The method is
      tested on hydrogen fluoride (HF) molecules confined in C60 fullerene cages
      themselves trapped in a nanotube to form a carbon peapod. The rotational degrees
      of freedom of the HF molecules and dipolar interactions between neighboring
      molecules are considered in our model Hamiltonian. Both screened and unscreened
      dipoles are simulated and results are obtained for the ground state and one
      excited state that is expected to be accessible via a far-infrared collective
      excitation. The effect of basis truncation on energetic and entanglement
      properties is examined and discussed in terms of size extensivity. It is
      empirically found that for unscreened dipoles, a total angular momentum cutoff
      that increases linearly with the number of rotors is required in order to obtain
      proper system size scaling of the chemical potential and entanglement entropy.
      Recent experiments [A. Krachmalnicoff et al., Nat. Chem. 8, 953 (2016)] suggest
      substantial screening of the HF dipole moment, so much smaller basis sets are
      required to obtain converged results in this realistic case. Static correlation
      functions are also computed and are shown to decay much quicker in the case of
      screened dipoles. Our variational results are also used to test the accuracy of
      perturbative and pairwise ansatz treatments.

PMID- 29471655
TI  - Long-lived transient anion of c-C4F8O.
AB  - We report partial cross sections for electron attachment to c-C4F8O, a gas with
      promising technological applications in free-electron-rich environments. The
      dissociative electron attachment leads to a number of anionic fragments resulting
      from complex bond-breaking and bond-forming processes. However, the anion with
      the highest abundance is the non-dissociated (transient) parent anion which is
      formed around 0.9 eV electron energy. Its lifetime reaches tens of microseconds.
      We discuss the origin of this long lifetime, the anion's strong interactions with
      other molecules, and the consequences for electron-scavenging properties of c
      C4F8O in denser environments, in particular for its use in mixtures with CO2 and
      N2.

PMID- 29471657
TI  - Time-dependent density functional theory description of total photoabsorption
      cross sections.
AB  - The time-dependent version of the density functional theory (TDDFT) has been used
      to calculate the total photoabsorption cross section of a number of molecules,
      namely, benzene, pyridine, furan, pyrrole, thiophene, phenol, naphthalene, and
      anthracene. The discrete electronic pseudo-spectra, obtained in a L2 basis set
      calculation were used in an analytic continuation procedure to obtain the
      photoabsorption cross sections. The ammonia molecule was chosen as a model system
      to compare the results obtained with TDDFT to those obtained with the linear
      response coupled cluster approach in order to make a link with our previous work
      and establish benchmarks.

PMID- 29471656
TI  - Cumulant expansions for measuring water exchange using diffusion MRI.
AB  - The rate of water exchange across cell membranes is a parameter of biological
      interest and can be measured by diffusion magnetic resonance imaging (dMRI). In
      this work, we investigate a stochastic model for the diffusion-and-exchange of
      water molecules. This model provides a general solution for the temporal
      evolution of dMRI signal using any type of gradient waveform, thereby
      generalizing the signal expressions for the Karger model. Moreover, we also
      derive a general nth order cumulant expansion of the dMRI signal accounting for
      water exchange, which has not been explored in earlier studies. Based on this
      analytical expression, we compute the cumulant expansion for dMRI signals for the
      special case of single diffusion encoding (SDE) and double diffusion encoding
      (DDE) sequences. Our results provide a theoretical guideline on optimizing
      experimental parameters for SDE and DDE sequences, respectively. Moreover, we
      show that DDE signals are more sensitive to water exchange at short-time scale
      but provide less attenuation at long-time scale than SDE signals. Our theoretical
      analysis is also validated using Monte Carlo simulations on synthetic structures.

PMID- 29471658
TI  - Excited-state dissociation dynamics of phenol studied by a new time-resolved
      technique.
AB  - Phenol is an important model molecule for the theoretical and experimental
      investigation of dissociation in the multistate potential energy surfaces. Recent
      theoretical calculations [X. Xu et al., J. Am. Chem. Soc. 136, 16378 (2014)]
      suggest that the phenoxyl radical produced in both the X and A states from the O
      H bond fission in phenol can contribute substantially to the slow component of
      photofragment translational energy distribution. However, current experimental
      techniques struggle to separate the contributions from different dissociation
      pathways. A new type of time-resolved pump-probe experiment is described that
      enables the selection of the products generated from a specific time window after
      molecules are excited by a pump laser pulse and can quantitatively characterize
      the translational energy distribution and branching ratio of each dissociation
      pathway. This method modifies conventional photofragment translational
      spectroscopy by reducing the acceptance angles of the detection region and
      changing the interaction region of the pump laser beam and the molecular beam
      along the molecular beam axis. The translational energy distributions and
      branching ratios of the phenoxyl radicals produced in the X, A, and B states from
      the photodissociation of phenol at 213 and 193 nm are reported. Unlike other
      techniques, this method has no interference from the undissociated hot molecules.
      It can ultimately become a standard pump-probe technique for the study of large
      molecule photodissociation in multistates.

PMID- 29471659
TI  - Thermodynamic properties of confined square-well fluids with multiple associating
      sites.
AB  - In this work, a molecular simulation study of confined hard-spheres particles
      with square-well (SW) attractive interactions with two and four associating SW
      sites based on the first-order perturbation form of Wertheim's theory is
      presented. An extended version of the Gibbs ensemble technique for inhomogeneous
      fluids [A. Z. Panagiotopoulos, Mol. Phys. 62, 701 (1987)] is used to predict the
      adsorption density profiles for associating fluids confined between opposite
      parallel walls. The fluid is confined in four kinds of walls: hard-wall, SW wall,
      Lennard-Jones (LJ) 12-6 wall potential, and LJ 10-4 wall potential. We analyze
      the behavior of the confined system for several supercritical temperatures as a
      function of variation of molecular parameters: potential range lambda, bulk
      densities rhob*, pore width H, cutoff range interaction rc*, and range of the
      potential and depth of the particle-wall (lambdaw, epsilonw*). Additionally, we
      include predictions for liquid-vapor coexistence of bulk associative particles
      and how their critical properties are modified by the presence of associative
      sites in the molecule. The molecular simulation data presented in this work are
      of prime importance to the development of theoretical approaches for
      inhomogeneous fluids as classical density functional theory. The simulation
      results presented here are resourceful for predicting adsorption isotherms of
      real associating fluids such as water.

PMID- 29471660
TI  - Molecular dynamics simulation for the test of calibrated OPLS-AA force field for
      binary liquid mixture of tri-iso-amyl phosphate and n-dodecane.
AB  - Tri-isoamyl phosphate (TiAP) has been proposed to be an alternative for tri-butyl
      phosphate (TBP) in the Plutonium Uranium Extraction (PUREX) process. Recently, we
      have successfully calibrated and tested all-atom optimized potentials for liquid
      simulations using Mulliken partial charges for pure TiAP, TBP, and dodecane by
      performing molecular dynamics (MD) simulation. It is of immense importance to
      extend this potential for the various molecular properties of TiAP and TiAP/n
      dodecane binary mixtures using MD simulation. Earlier, efforts were devoted to
      find out a suitable force field which can explain both structural and dynamical
      properties by empirical parameterization. Therefore, the present MD study reports
      the structural, dynamical, and thermodynamical properties with different mole
      fractions of TiAP-dodecane mixtures at the entire range of mole fraction of 0-1
      employing our calibrated Mulliken embedded optimized potentials for liquid
      simulation (OPLS) force field. The calculated electric dipole moment of TiAP was
      seen to be almost unaffected by the TiAP concentration in the dodecane diluent.
      The calculated liquid densities of the TiAP-dodecane mixture are in good
      agreement with the experimental data. The mixture densities at different
      temperatures are also studied which was found to be reduced with temperature as
      expected. The plot of diffusivities for TiAP and dodecane against mole fraction
      in the binary mixture intersects at a composition in the range of 25%-30% of TiAP
      in dodecane, which is very much closer to the TBP/n-dodecane composition used in
      the PUREX process. The excess volume of mixing was found to be positive for the
      entire range of mole fraction and the excess enthalpy of mixing was shown to be
      endothermic for the TBP/n-dodecane mixture as well as TiAP/n-dodecane mixture as
      reported experimentally. The spatial pair correlation functions are evaluated
      between TiAP-TiAP and TiAP-dodecane molecules. Further, shear viscosity has been
      computed by performing the non-equilibrium molecular dynamics employing the
      periodic perturbation method. The calculated shear viscosity of the binary
      mixture is found to be in excellent agreement with the experimental values. The
      use of the newly calibrated OPLS force field embedding Mulliken charges is shown
      to be equally reliable in predicting the structural and dynamical properties for
      the mixture without incorporating any arbitrary scaling in the force field or
      Lennard-Jones parameters. Further, the present MD simulation results demonstrate
      that the Stokes-Einstein relation breaks down at the molecular level. The present
      methodology might be adopted to evaluate the liquid state properties of an
      aqueous-organic biphasic system, which is of great significance in the
      interfacial science and technology.

PMID- 29471661
TI  - Path integrals with higher order actions: Application to realistic chemical
      systems.
AB  - Quantum thermodynamic parameters can be determined using path integral Monte
      Carlo (PIMC) simulations. These simulations, however, become computationally
      demanding as the quantum nature of the system increases, although their
      efficiency can be improved by using higher order approximations to the thermal
      density matrix, specifically the action. Here we compare the standard, primitive
      approximation to the action (PA) and three higher order approximations, the
      Takahashi-Imada action (TIA), the Suzuki-Chin action (SCA) and the Chin action
      (CA). The resulting PIMC methods are applied to two realistic potential energy
      surfaces, for H2O and HCN-HNC, both of which are spectroscopically accurate and
      contain three-body interactions. We further numerically optimise, for each
      potential, the SCA parameter and the two free parameters in the CA, obtaining
      more significant improvements in efficiency than seen previously in the
      literature. For both H2O and HCN-HNC, accounting for all required potential and
      force evaluations, the optimised CA formalism is approximately twice as efficient
      as the TIA formalism and approximately an order of magnitude more efficient than
      the PA. The optimised SCA formalism shows similar efficiency gains to the CA for
      HCN-HNC but has similar efficiency to the TIA for H2O at low temperature. In H2O
      and HCN-HNC systems, the optimal value of the a1 CA parameter is approximately
      13, corresponding to an equal weighting of all force terms in the thermal density
      matrix, and similar to previous studies, the optimal alpha parameter in the SCA
      was ~0.31. Importantly, poor choice of parameter significantly degrades the
      performance of the SCA and CA methods. In particular, for the CA, setting a1 = 0
      is not efficient: the reduction in convergence efficiency is not offset by the
      lower number of force evaluations. We also find that the harmonic approximation
      to the CA parameters, whilst providing a fourth order approximation to the
      action, is not optimal for these realistic potentials: numerical optimisation
      leads to better approximate cancellation of the fifth order terms, with deviation
      between the harmonic and numerically optimised parameters more marked in the more
      quantum H2O system. This suggests that numerically optimising the CA or SCA
      parameters, which can be done at high temperature, will be important in fully
      realising the efficiency gains of these formalisms for realistic potentials.

PMID- 29471662
TI  - Pressure effect on micellization of non-ionic surfactant Triton X-100.
AB  - Micellar aggregates can be arranged in new types of conformational assemblies
      when they are isotropically compressed. Thus, the pressure effects in the
      underlying fundamental interactions leading to self-assembly of micellar
      aggregates can be represented by changes in the phase boundaries with increasing
      pressure. In this paper, we have employed molecular dynamics simulations to study
      the self-assembly of micelles composed of the non-ionic surfactant Triton X-100
      at the atomic scale, monitoring the changes in the solvation dynamics when the
      micelles are subjected to a wide range of hydrostatic pressures. The
      computational molecular model was capable of self-assembling and forming a non
      ionic micelle, which subsequently was coupled to a high-pressure barostat
      producing a geometric transition of the micelle due to changes in the solvation
      dynamics. Accordingly, under a high pressure regime, the hydrogen bonds are
      redistributed, the water density is modified, and water acts as an unstructured
      liquid, capable of penetrating into the micelle.

PMID- 29471663
TI  - Quantum coherence in the reflection of above barrier wavepackets.
AB  - The quantum phenomenon of above barrier reflection is investigated from a time
      dependent perspective using Gaussian wavepackets. The transition path time
      distribution, which in principle is experimentally measurable, is used to study
      the mean flight times ?t?R and ?t?T associated with the reflection and the
      transmission over the barrier paying special attention to their dependence on the
      width of the barrier. Both flight times, and their difference Deltat, exhibit two
      distinct regimes depending on the ratio of the spatial width of the incident
      wavepacket and the length of the barrier. When the ratio is larger than unity,
      the reflection and transmission dynamics are coherent and dominated by the
      resonances above the barrier. The flight times ?t?R/T and the flight time
      difference Deltat oscillate as a function of the barrier width (almost in phase
      with the transmission probability). These oscillations reflect a momentum
      filtering effect related to the coherent superposition of the reflected and
      transmitted waves. For a ratio less than unity, the barrier reflection and
      transmission dynamics are incoherent and the oscillations are absent. The barrier
      width which separates the coherent and incoherent regimes is identified
      analytically. The oscillatory structure of the time difference Deltat as a
      function of the barrier width in the coherent regime is absent when considered in
      terms of the Wigner phase time delays for reflection and transmission. We
      conclude that the Wigner phase time does not correctly describe the temporal
      properties of above barrier reflection. We also find that the structure of the
      reflected and transmitted wavepackets depends on the coherence of the process. In
      the coherent regime, the wavepackets can have an overlapping peak structure, but
      the peaks are not fully resolved. In the incoherent regime, the wavepackets split
      in time into distinct separated Gaussian like waves, each one reflecting the
      number of times the wavepacket crosses the barrier region before exiting. A
      classical Wigner approximation, using classical trajectories which upon reaching
      an edge of the barrier are reflected or transmitted as if the edge was a step
      potential, is quantitative in the incoherent regime. The implications of the
      coherence observed on resonance reactive scattering are discussed.

PMID- 29471664
TI  - Anhydrosaccharides-A new class of the fragile plastic crystals.
AB  - In this paper, 1,6-anhydro-beta-D-glucopyranose (anhGLU), 1,6-anhydro-beta-D
      mannopyranose (anhMAN), and 1,6-anhydro-beta-D-galactopyranose (anhGAL), three
      new materials that form the Orientationally Disordered Crystal (ODIC) phase, have
      been thoroughly investigated using various experimental techniques. All
      measurements clearly indicated that these compounds possess a series of very
      interesting physical properties that are considerably different than those
      reported for ordinary plastic crystals. X-Ray diffraction investigations have
      revealed enormously long-range static correlations between molecules, reaching
      even 120 A. Moreover, dielectric studies showed that besides Freon 113, the
      investigated anhydrosaccharides are the most fragile systems that form the ODIC
      phase. Further analysis of Fourier transform infrared spectra indicated that such
      peculiar behavior of anhydrosaccharides might be closely related to
      multidirectional H-bonds of various strengths that most likely affect the number
      of available conformations, density states, and the potential barriers in the
      energy landscape of these compounds. This is consistent with the results from
      previous reports [L. C. Pardo, J. Chem. Phys. 124, 124911 (2006) and Th. Bauer et
      al., J Chem. Phys. 133, 144509 (2010)] showing that the higher fragility of Freon
      112 as well as a mixture of 60% succinonitrile and 40% glutaronitrile (60SN-40GN)
      can be closely related to the enhanced conformational ability and additional
      disorder introduced by various substituents, which further make energy landscape
      more complex. Finally, by studying the properties of 2,3,4-tri-O-acetyl-1,6
      anhydro-beta-D-glucopyranose (ac-anhGLU) it was found that besides the shape of
      the molecules, H-bonds or generally strong intermolecular interactions are
      extremely important parameters contributing to the ability to form the plastic
      phase. This is in line with current observations that in most cases the ODIC
      phase is created in highly interacting compounds.

PMID- 29471665
TI  - Communication: The electronic entropy of charged defect formation and its impact
      on thermochemical redox cycles.
AB  - The ideal material for solar thermochemical water splitting, which has yet to be
      discovered, must satisfy stringent conditions for the free energy of reduction,
      including, in particular, a sufficiently large positive contribution from the
      solid-state entropy. By inverting the commonly used relationship between defect
      formation energy and defect concentration, it is shown here that charged defect
      formation causes a large electronic entropy contribution manifesting itself as
      the temperature dependence of the Fermi level. This result is a general feature
      of charged defect formation and motivates new materials design principles for
      solar thermochemical hydrogen production.

PMID- 29471666
TI  - Rural-urban differences in exposure to adverse childhood experiences among South
      Carolina adults.
AB  - INTRODUCTION: Adverse childhood experiences (ACEs) are traumatic events that
      occur in a child's life between birth and 18 years. Exposure to one or more ACE
      has been linked to participation in risky health behaviors and the experience of
      chronic health conditions in adulthood. The risk for poor outcomes increases as
      the number of ACEs experienced increases. This research investigates rural-urban
      differences in exposure to ACEs using a sample from a representative southern US
      state, South Carolina. METHODS: Using data from the 2014-2015 South Carolina
      Behavioral Risk Factor Surveillance System &#40;BRFSS&#41; and residential
      rurality based on UICs, ACE exposure among South Carolina adults was tabulated by
      urban versus rural residence and selected other demographic characteristics.
      Using standard descriptive statistics, frequencies and proportions were
      calculated for each categorical variable. Multivariable regression modeling was
      used to examine the impact of residential rurality and selected sociodemographic
      characteristics on overall and specific types of ACE exposure. All analyses used
      survey sampling weights that accounted for the BRFSS sampling strategy. RESULTS:
      The analytic sample of 18 176 respondents comprised 15.9% rural residents. Top
      reported ACEs for both rural and urban residents were the same: parental
      divorce/separation, emotional abuse, and household substance use. Compared to
      urban residents, a higher proportion of rural respondents reported experiencing
      no ACEs (41.4% vs 38.3%, p<0.01). The prevalence of four or more ACEs in rural
      respondents was 15.0%; in comparison, 17.6% of urban respondents had four or more
      ACEs (p<0.01). In logistic regression predicting exposure to four or more ACEs
      and adjusting for sex, age, race/ethnicity, education, and income, rural
      respondents were less likely than urban respondents to report four or more ACEs
      (adjusted odds ratio 0.75, 95% confidence interval 0.74-0.75). CONCLUSIONS:
      Despite reporting less ACE exposure than urban counterparts, almost 60% of rural
      residents reported at least one ACE and 15% reported experiencing four or more
      ACEs. In contrast to urban residents, rural residents may experience more social
      connections within their families and communities, which may influence ACE
      exposure; however, care coordination, social support services, and access to
      health care are limited in rural areas. Thus, families in rural areas may be less
      equipped to mitigate and manage the effects of ACEs. Findings from this study
      thus suggest that interventions to prevent ACE exposure are just as needed in
      rural southern communities as they are in urban southern communities. Topics
      important for future research could include an examination of ACEs in rural
      communities in terms of individuals' health outcomes and their access to health
      care, as well as the role of protective factors. Programs and policies that
      assist in ACE prevention in rural areas are important to reducing these
      multigenerational threats to health and wellbeing.

PMID- 29471667
TI  - Review of differentiated approaches to antiretroviral therapy distribution.
AB  - In response to global trends of maximizing the number of patients receiving
      antiretroviral therapy (ART), this review summarizes literature describing
      differentiated models of ART distribution at facility and community levels in
      order to highlight promising strategies and identify evidence gaps. Databases and
      gray literature were searched, yielding thirteen final articles on differentiated
      ART distribution models supporting stable adult patients. Of these, seven
      articles focused on distribution at facility level and six at community level.
      Findings suggest that differentiated models of ART distribution contribute to
      higher retention, lower attrition, and less loss to follow-up (LTFU). These
      models also reduced patient wait time, travel costs, and time lost from work for
      drug pick-up. Facility- and community-level ART distribution models have the
      potential to extend treatment availability, enable improved access and adherence
      among people living with HIV (PLHIV), and facilitate retention in treatment and
      care. Gaps remain in understanding the desirability of these models for PLHIV,
      and the need for more information the negative and positive impacts of stigma,
      and identifying models to reach traditionally marginalized groups such as key
      populations and youth. Replicating differentiated care so efforts can reach more
      PLHIV will be critical to scaling these approaches across varying contexts.

PMID- 29471668
TI  - Explained and unexplained racial and regional inequality in obesity prevalence in
      the United States.
AB  - OBJECTIVE: There are substantial racial and regional disparities in obesity
      prevalence in the United States. This study partitioned the mean Body Mass Index
      (BMI) and obesity prevalence rate gaps between non-Hispanic blacks and non
      Hispanic whites into the portion attributable to observable obesity risk factors
      and the remaining portion attributable to unobservable factors at the national
      and the state levels in the United States (U.S.) in 2010. DESIGN: This study used
      a simulated micro-population dataset combining common information from the
      Behavioral Risk Factor Surveillance System and the U.S. Census data to obtain a
      reliable, large sample representing the adult populations at the national and
      state levels. It then applied a reweighting decomposition method to decompose the
      black-white mean BMI and obesity prevalence disparities at the national and state
      levels into the portion attributable to the differences in distribution of
      observable obesity risk factors and the remaining portion unexplainable with risk
      factors. RESULTS: We found that the observable differences in distribution of
      known obesity risk factors explain 18.5% of the mean BMI difference and 20.6% of
      obesity prevalence disparities between non-Hispanic blacks and non-Hispanic
      whites. There were substantial variations in how much the differences in
      distribution of known obesity risk factors can explain black-white gaps in mean
      BMI (-67.7% to 833.6%) and obesity prevalence (-278.5% to 340.3%) at the state
      level. CONCLUSION: The results from this study demonstrate that known obesity
      risk factors explain a small proportion of the racial, ethnic and between-state
      disparities in obesity prevalence in the United States. Future etiologic studies
      are required to further understand the causal factors underlying obesity and
      racial, ethnic and geographic disparities.

PMID- 29471669
TI  - Optimizing stress responses with reappraisal and mindset interventions: an
      integrated model.
AB  - BACKGROUND: The dominant perspective in society is that stress has negative
      consequences, and not surprisingly, the vast majority of interventions for coping
      with stress focus on reducing the frequency or severity of stressors. However,
      the effectiveness of stress attenuation is limited because it is often not
      possible to avoid stressors, and avoiding or minimizing stress can lead
      individuals to miss opportunities for performance and growth. Thus, during
      stressful situations, a more efficacious approach is to optimize stress responses
      (i.e., promote adaptive, approach-motivated responses). Objectives and
      Conclusions: In this review, we demonstrate how stress appraisals (e.g.,
      [Jamieson, J. P., Nock, M. K., & Mendes, W. B. (2012). Mind over matter:
      reappraising arousal improves cardiovascular and cognitive responses to stress.
      Journal of Experimental Psychology: General, 141(3), 417-422. doi:
      10.1037/a0025719 ]) and stress mindsets (e.g., [Crum, A. J., Salovey, P., &
      Achor, S. (2013). Rethinking stress: The role of mindsets in determining the
      stress response. Journal of Personality and Social Psychology, 104(4), 716-733.
      doi: 10.1037/a0031201 ]) can be used as regulatory tools to optimize stress
      responses, facilitate performance, and promote active coping. Respectively, these
      interventions invite individuals to (a) perceive stress responses as functional
      and adaptive, and (b) see the opportunity inherent in stress. We then propose a
      novel integration of reappraisal and mindset models to maximize the utility and
      effectiveness of stress optimization. Additionally, we discuss future directions
      with regard to how stress responses unfold over time and between people to impact
      outcomes in the domains of education, organizations, and clinical science.

PMID- 29471670
TI  - Utility of intravoxel incoherent motion magnetic resonance imaging and arterial
      spin labeling for recurrent glioma after bevacizumab treatment.
AB  - Background Detecting recurrence of glioma on magnetic resonance imaging (MRI) is
      getting more and more important, especially after administration of new anti
      tumor agent. However, it is still hard to identify. Purpose To examine the
      utility of intravoxel incoherent motion (IVIM) MRI and arterial spin labeling
      cerebral blood flow (ASL-CBF) for recurrent glioma after initiation of
      bevacizumab (BEV) treatment. Material and Methods Thirteen patients (7 men, 6
      women; age range = 41-82 years) with glioma (high grade, n = 11; low grade, n =
      2) were enrolled in the study. IVIM parameters including apparent diffusion
      coefficient (ADC), true diffusion coefficient (D), and perfusion fraction (f)
      were obtained with 14 different b-values. We identified tumor progression during
      BEV therapy by MRI monitoring consisting of diffusion-weighted imaging (DWI),
      fluid-attenuated inversion recovery (FLAIR) imaging, and contrast-enhanced T1
      weighted (CE-T1W) imaging by measuring tumor area. We also measured each
      parameter of IVIM and ASL-CBF, and calculated relative ADC (rADC), relative D
      (rD), relative f (rf), and relative CBF (rCBF) by obtaining the ratio between
      each area and the contralateral cerebral white matter. We calculated the rate of
      change (Delta) by subtracting values from those from the preceding MRI study, and
      obtained Spearman's rank correlation coefficient (rs). Results Tumor progression
      was identified in nine patients (high grade, n = 7; low grade, n = 2). Negative
      correlations were identified between DeltarD and DeltaDWI area (rs = -0.583), and
      between DeltarD and DeltaCE-T1W imaging area (rs = -0.605). Conclusion Tumor
      progression after BEV treatment can be identified by decreasing rD.

PMID- 29471672
TI  - Association of physical inactivity with hypertension and low educational level in
      people living with HIV / AIDS.
AB  - The aim of this study was to determine the prevalence of physical inactivity and
      whether it is associated with sociodemographic, lifestyle, clinical,
      anthropometric, and body composition variables in people living with HIV/AIDS
      (PLWHA). This study makes use of data from a cohort of 288 adults aged >=19
      years, conducted between October 2009 and July 2011. The variables studied were
      sex, age, education, income, skin color, tobacco use, alcohol intake, body mass
      index, body fat percentage, waist circumference, and waist-hip ratio, length of
      HIV/AIDS diagnosis, use of antiretroviral therapy and length of its use, CD4,
      hypertension (HT) and diabetes mellitus. Physical inactivity was defined as a
      score below 600 metabolic equivalent minutes/week according to the International
      Physical Activity Questionnaire - Short Version. Poisson multiple regression was
      applied in the multivariate analysis with a significance level of 5%. The
      prevalence of physical inactivity was 44.1%. Education of <=4 years of study
      (prevalence ratio [PR]: 1.71) and HT (PR: 1.49) were associated with physical
      inactivity. Physical inactivity was highly prevalent in PLWHA and associated with
      low educational level and HT. We highlight the simultaneous association between
      two cardiometabolic risk factors, HT and physical inactivity.

PMID- 29471671
TI  - Cholesterol-enriched membrane microdomains are needed for insulin signaling and
      proliferation in hepatic cells.
AB  - Hepatocyte proliferation during liver regeneration is a well-coordinated process
      regulated by the activation of several growth factor receptors, including the
      insulin receptor (IR). The IR can be localized in part to cholesterol-enriched
      membrane microdomains, but the role of such domains in insulin-mediated events in
      hepatocytes is not known. We investigated whether partitioning of IRs into
      cholesterol-enriched membrane rafts is important for the mitogenic effects of
      insulin in the hepatic cells. IR and lipid rafts were labeled in HepG2 cells and
      primary rat hepatocytes. Membrane cholesterol was depleted in vitro with metyl
      beta-cyclodextrin (MbetaCD) and in vivo with lovastatin. Insulin-induced calcium
      (Ca2+) signals studies were examined in HepG2 cells and in freshly isolated rat
      hepatocytes as well as in whole liver in vivo by intravital confocal imaging.
      Liver regeneration was studied by 70% partial hepatectomy (PH), and hepatocyte
      proliferation was assessed by PCNA staining. A subpopulation of IR was found in
      membrane microdomains enriched in cholesterol. Depletion of cholesterol from
      plasma membrane resulted in redistribution of the IR along the cells, which was
      associated with impaired insulin-induced nuclear Ca2+ signals, a signaling event
      that regulates hepatocyte proliferation. Cholesterol depletion also led to ERK1/2
      hyper-phosphorylation. Lovastatin administration to rats decreased hepatic
      cholesterol content, disrupted lipid rafts and decreased insulin-induced Ca2+
      signaling in hepatocytes, and delayed liver regeneration after PH. Therefore,
      membrane cholesterol content and lipid rafts integrity showed to be important for
      the proliferative effects of insulin in hepatic cells. NEW & NOTEWORTHY One of
      insulin's actions is to stimulate liver regeneration. Here we show that a
      subpopulation of insulin receptors is in a specialized cholesterol-enriched
      region of the cell membrane and this subfraction is important for insulin's
      proliferative effects.

PMID- 29471673
TI  - Identifying Additional Risk Factors for Thrombosis and Pregnancy Morbidities
      Among Antiphospholipid Antibodies Carriers.
AB  - The evaluation of thrombotic and pregnancy risks associated with antiphospholipid
      antibodies (aPL)in individual patients without antiphospholipid syndrome (APS)
      clinical manifestation is challenging. Our aim is to identify additional risk
      factors or potential candidate "second hits" for APS clinical events in a large
      cohort of ethnically diverse aPL-positive patients. We included 219 consecutive
      aPL-positive patients who attended clinic at our institution. All patients had at
      least 1 persistent high titer (>=99 percentiles) aPL. Independent risk factors
      for thrombosis and pregnancy morbidities among patients with positive aPL were
      evaluated. When assessing risk factors associated with pregnancy morbidities,
      only female controls of reproductive age (age <=45) were used. Pearson chi2
      analysis and multivariable logistic regression were used to evaluate correlation
      between different risk factors and clinical manifestations. Of the 219 aPL
      positive patients, 120 (54.8%) patients had criteria APS clinical manifestations
      and 99 patients did not. A total of 46.1% were Caucasian, 26.4% of African
      descent, 16.9% Hispanic, 1.8% Asian, and 8.7% were unspecified. Among traditional
      risk factors and signs of endothelial injury, only hypertension demonstrated an
      independent association with arterial thrombosis (odds ratio [OR] = 3.826, 95%
      confidence interval [CI]: 1.597-9.167, P = .0026), and lupus anticoagulant (LA)
      demonstrated an independent association with venous thrombosis (OR = 3.308, 95%
      CI: 1.544-7.085, P = .0021). None of the evaluated risk factors demonstrated a
      significant association with pregnancy morbidity. Hypertension is a potential
      predictor of arterial thrombosis and the presence of LA is a potential predictor
      of venous thrombosis in aPL-positive patients.

PMID- 29471674
TI  - Concomitant Versus Individual Administration of Antithrombin and Thrombomodulin
      for Sepsis-Induced Disseminated Intravascular Coagulation: A Nationwide Japanese
      Registry Study.
AB  - BACKGROUND: Antithrombin and recombinant human thrombomodulin (rhTM) are
      individually reported to improve survival in sepsis-induced disseminated
      intravascular coagulation (DIC). However, continuing controversy exists as to
      which agent is superior and whether concomitant therapy is superior to individual
      administration. METHODS: This post hoc analysis included adult patients with
      sepsis-induced DIC from a nationwide multicenter registry database in Japan. We
      categorized patients into 4 groups: patients who received (1) individual
      administration of antithrombin, (2) individual administration of rhTM, (3) both,
      and (4) neither. In-hospital mortality was compared between every 2 groups among
      the 4 groups by Cox proportional hazards model adjusted with propensity scores.
      RESULTS: In total, 1432 patients with sepsis-induced DIC were included. Although
      both antithrombin and rhTM were associated better outcome compared with no
      anticoagulants, mortality benefits were similar between each individual
      anticoagulant. Similarly, no significant difference in mortality was detected
      between individual administrations and concomitant therapy. CONCLUSION:
      Antithrombin and rhTM might have comparable efficacy in reducing mortality in
      patients with sepsis; however, concomitant therapy appeared to offer no
      additional survival benefit.

PMID- 29471675
TI  - Alterations in nucleotide-binding oligomerization domain-2 expression, pathway
      activation, and cytokine production in Yao syndrome.
AB  - Yao syndrome (YAOS) is a systemic autoinflammatory disease (SAID), formerly
      termed nucleotide-binding oligomerization domain-2 (NOD2)-associated
      autoinflammatory disease. Due to the recent identification of YAOS, the molecular
      mechanisms underlying its disease pathogenesis are unclear. With specific NOD2
      variants as characteristic genotypic features of YAOS, our study examined NOD2
      expression, transcript splicing, signaling pathway activation, and cytokine
      profiles in peripheral blood mononuclear cells (PBMCs) from 10 YAOS patients and
      six healthy individuals. All participants were genotyped for NOD2 variants; all
      YAOS patients were heterozygous for the NOD2 IVS8+158 variant (IVS8+158) and four
      patients also carried a concurrent NOD2 R702W variant (IVS8+158/R702W haplotype).
      Resembling other SAIDs, plasma levels of TNFalpha, IL-1beta, IL-6, IFNgamma, and
      S100A12 were unaltered in YAOS patients. Intron-8 splicing of NOD2 transcripts
      was unaffected by carriage of NOD2 IVS8+158. However, NOD2 transcript level and
      basal p38 mitogen-activated protein kinase (MAPK) activity were significantly
      elevated in PBMCs from IVS8+158 YAOS patients. Moreover, these patients' cells
      had elevated basal IL-6 secretion that was enhanced by muramyl dipeptide (MDP)
      stimulation. Tocilizumab treatment of a YAOS IVS8+158 patient resulted in marked
      clinical improvement. In contrast, MDP-stimulated NF-kappaB activity was uniquely
      suppressed in haplotype IVS8+158/R702W patients, as was TNFalpha secretion. Our
      study demonstrates for the first time that NOD2 expression and pathway activation
      are aberrant in YAOS, and specific NOD2 genotypes result in distinct NOD2
      expression and cytokine profiles. These findings may also help select therapeutic
      strategies in the future.

PMID- 29471676
TI  - Results and challenges of immune checkpoint inhibitors in colorectal cancer.
AB  - INTRODUCTION: Colorectal cancer (CRC) is the third most commonly diagnosed cancer
      worldwide and clinical outcome has improved substantially during the last two
      decades with targeted therapies. The immune system has a major role in cancers,
      especially the CD8 + T cells specific to tumor antigens. However, tumors can
      escape immune response by different mechanisms including upregulation of
      inhibitory immune checkpoint receptors, such as well-known Programmed cell Death
      protein-1 (PD-1)/Programmed cell Death Ligand 1 (PD-L1) interaction, leading CD8
      + T cells to a state of anergy. Immunotherapy, with the so-called immune
      checkpoint inhibitors (CPIs), has recently been approved in treatment of multiple
      cancers due to its prolonged disease control and acceptable toxicities. The
      recent groundbreaking success involving anti-PD-1 CPIs in metastatic CRC with
      deficient mismatch repair system (dMMR) is promising, with several trials
      ongoing. Major challenges are ahead in order to determine how, when and for which
      patients we should use these CPIs in CRC. Areas covered: This review highlights
      some promises and challenges concerning personalized immunotherapy in CRC. First
      results and ongoing breakthrough trials are presented. The crucial role of
      biomarkers in selecting patient is also discussed. Expert opinion: As of now,
      dMMR and POLE mutations (DNA polymerase epsilon) with ultramutator phenotype are
      the most powerful predictive biomarkers of CPI efficacy. The most challenging
      issue is pMMR mCRC and determination of how to convert a 'nonimmunogenic'
      neoplasm into an 'immunogenic' neoplasm, a combination of CPIs with radiation or
      MEK inhibitor probably being the most relevant strategy. Next-generation
      sequencing (NGS) assays to quantify mutational load could be more reliable
      predictive biomarkers of CPIs efficacy than PD-L1 expression or immune scores.

PMID- 29471677
TI  - Association between coping strategies, social support, and depression and anxiety
      symptoms among rural Ugandan women living with HIV/AIDS.
AB  - Poor mental health detrimentally affects quality of life among women living with
      HIV/AIDS. An improved understanding of how coping and social support relate to
      depression and anxiety in this population can facilitate the design and
      implementation of appropriate mental health treatment and support services.
      Secondary analysis was conducted on baseline data from 288 HIV-positive women
      enrolled in a parenting intervention in Uganda. Depression and anxiety symptoms,
      social support, and coping were assessed with the Hopkins Symptom Checklist and
      adapted versions of the Multidimensional Scale for Perceived Social Support and
      Ways of Coping Questionnaire. General linear regression models were used to
      estimate associations between coping and mental health. Based on report of
      elevated symptoms, approximately 10% of women were categorized as having
      clinically-relevant depression or anxiety. Emotion-focused (EF: p < .001) and
      problem-focused (PF: p = .01) coping were associated with more depressive
      symptoms while greater family support (EF: p = .002; PF: p = .003) was associated
      with fewer depression symptoms. More anxiety symptoms were associated with
      reporting both coping strategies (EF: p < .001; PF: p = .02) and higher community
      support (EF&PF: p = .01). The cross-sectional nature of the study limits our
      ability to rule out the role of reverse causation in the significant relationship
      between coping and mental health. Findings do suggest that high family support
      can be protective against depression and anxiety symptoms among women living with
      HIV.

PMID- 29471678
TI  - Early versus delayed pulmonary rehabilitation: A randomized controlled trial -
      Can we do it?

PMID- 29471679
TI  - ARISE: A Phase 3 randomized trial of erenumab for episodic migraine.
AB  - Background Calcitonin gene-related peptide plays an important role in migraine
      pathophysiology. Erenumab, a human monoclonal antibody that inhibits the
      calcitonin gene-related peptide receptor, is being evaluated for migraine
      prevention. Methods In this randomized, double-blind, placebo-controlled, phase 3
      study, 577 adults with episodic migraine were randomized to placebo or 70 mg
      erenumab; 570 patients were included in efficacy analyses. Primary endpoint was
      change in monthly migraine days. Secondary endpoints were >=50% reduction in
      monthly migraine days, change in acute migraine-specific medication treatment
      days, and >=5-point reduction in Physical Impairment and Impact on Everyday
      Activities domain scores measured by the Migraine Physical Function Impact Diary.
      All endpoints assessed change from baseline at month 3. Results Patients
      receiving erenumab experienced -2.9 days change in monthly migraine days,
      compared with -1.8 days for placebo, least-squares mean (95% CI) treatment
      difference of -1.0 (-1.6, -0.5) ( p < 0.001). A >= 50% reduction in monthly
      migraine days was achieved by 39.7% (erenumab) and 29.5% (placebo) of patients
      (OR:1.59 (95% CI: 1.12, 2.27) ( p = 0.010). Migraine-specific medication
      treatment days were reduced by -1.2 (erenumab) and -0.6 (placebo) days, a
      treatment difference of -0.6 (-1.0, -0.2) ( p = 0.002). The >=5-point reduction
      rates in Migraine Physical Function Impact Diary - Physical Impairment were 33.0%
      and 27.1% (OR:1.33 (0.92, 1.90) ( p = 0.13) and in Migraine Physical Function
      Impact Diary - Everyday Activities were 40.4% and 35.8% (OR:1.22 (0.87, 1.71) ( p
      = 0.26). Safety and adverse event profiles of erenumab were similar to placebo.
      Most frequent adverse events were upper respiratory tract infection, injection
      site pain, and nasopharyngitis. Conclusions As a preventive treatment of episodic
      migraine, erenumab at a dosage of 70 mg monthly significantly reduced migraine
      frequency and acute migraine-specific medication use. (Funded by Amgen). Trial
      registration ClinicalTrials.gov, NCT02483585.

PMID- 29471680
TI  - Proteomic profiling of extracellular vesicles released from vascular smooth
      muscle cells during initiation of phosphate-induced mineralization.
AB  - : Purpose/Aim: Elevated serum phosphate is one of the major factors contributing
      to vascular calcification. Studies suggested that extracellular vesicles released
      from vascular smooth muscle cells significantly contribute to the initiation and
      progression of this pathology. Recently, we have demonstrated that elevated
      phosphate stimulates release of extracellular vesicles from osteogenic cells at
      the initiation of the mineralization process. Here, we used MOVAS cell line as an
      in vitro model of vascular calcification to examine whether vascular smooth
      muscle cells respond to high phosphate levels in a similar way and increase
      formation of extracellular vesicles. MATERIALS AND METHODS: Vesicles residing in
      extracellular matrix as well as vesicles released to culture medium were
      evaluated by nanoparticle tracking analyses. In addition, using mass spectrometry
      and protein profiling, protein composition of extracellular vesicles released by
      MOVAS cells under standard growth conditions and upon exposure to high phosphate
      was compared. RESULTS: Significant increase of the number of extracellular
      vesicles was detected after 72 h of exposure of cells to high phosphate. Elevated
      phosphate levels also affected protein composition of extracellular vesicles
      released from MOVAS cells. Finally, the comparative analyses of proteins in
      extracellular vesicles isolated from extracellular matrix and from conditioned
      medium identified significant differences in protein composition in these two
      groups of extracellular vesicles. CONCLUSIONS: Results of this study demonstrate
      that exposure of MOVAS cells to high phosphate levels stimulates the release of
      extracellular vesicles and changes their protein composition.

PMID- 29471681
TI  - rA1M-035, a Physicochemically Improved Human Recombinant alpha1-Microglobulin,
      Has Therapeutic Effects in Rhabdomyolysis-Induced Acute Kidney Injury.
AB  - AIMS: Human alpha1-microglobulin (A1M) is an endogenous reductase and radical-
      and heme-binding protein with physiological antioxidant protective functions.
      Recombinant human A1M (rA1M) has been shown to have therapeutic properties in
      animal models of preeclampsia, a pregnancy disease associated with oxidative
      stress. Recombinant A1M, however, lacks glycosylation, and shows lower solubility
      and stability than A1M purified from human plasma. The aims of this work were to
      (i) use site-directed mutagenesis to improve the physicochemical properties of
      rA1M, (ii) demonstrate that the physicochemically improved rA1M displays full in
      vitro cell protective effects as recombinant wild-type A1M (rA1M-wt), and (iii)
      show its therapeutic potential in vivo against acute kidney injury (AKI), another
      disease associated with oxidative stress. RESULTS: A novel recombinant A1M
      variant (rA1M-035) with three amino acid substitutions was constructed,
      successfully expressed, and purified. rA1M-035 had improved solubility and
      stability compared with rA1M-wt, and showed intact in vitro heme-binding,
      reductase, antioxidation, and cell protective activities. Both rA1M-035 and rA1M
      wt showed, for the first time, potential in vivo protective effects on kidneys
      using a mouse rhabdomyolysis glycerol injection model of AKI. INNOVATION: A novel
      recombinant A1M-variant, rA1M-035, was engineered. This protein showed improved
      solubility and stability compared with rA1M-wt, full in vitro functional
      activity, and potential protection against AKI in an in vivo rhabdomyolysis mouse
      model. CONCLUSION: The new rA1M-035 is a better drug candidate than rA1M-wt for
      treatment of AKI and preeclampsia in human patients. Antioxid. Redox Signal. 00,
      000-000.

PMID- 29471682
TI  - The role of spousal relationships in fibromyalgia patients' quality of life.
AB  - Fibromyalgia (FM) is a chronic pain syndrome that includes debilitating symptoms
      such as widespread pain and tenderness, fatigue, and poor physical functioning.
      Research has shown FM patients' choice of coping style and relationship quality
      with their spouse can impact their mental quality of life (QoL), but no known
      study has examined the protective nature of relationship quality and coping
      behaviors on both patient physical and mental QoL in the context of chronic pain.
      We examined 204 patients with FM on the (a) roles of coping styles and
      relationship quality on patient quality of life, and (b) moderating effect of
      relationship quality on the association between negative coping style and patient
      QoL. A series of multiple regressions found patients' coping styles were not
      significantly associated with physical QoL, but were significantly associated
      with mental QoL. Patients' relationship quality with their spouse was
      significantly associated with mental QoL, but not physical QoL and no significant
      interactions with negative coping style were found. Our results emphasize the
      importance of coping styles and relationship quality between patients and their
      spouses in the context of chronic pain. Clinicians can incorporate the patient's
      relationship as part of a more holistic approach to care and improving outcomes.

PMID- 29471683
TI  - Uso Del Condon en Adolescentes Nahuas, un Modelo Explicativo.
AB  - En Mexico, la poblacion indigena supera los siete millones de habitantes, en
      Puebla el grupo mas representativo es el Nahuatl. Sin embargo, las condiciones de
      vida, salud, educacion y transporte son precarias para esta poblacion. En los
      adolescentes, las responsabilidades como el matrimonio, la familia y los
      compromisos ante la comunidad, favorecen conductas de riesgo sexual que
      dificultan su desarrollo economico, social y reproductivo. El objetivo fue
      proponer un modelo explicativo del uso del condon en adolescentes nahuas. Metodo.
      Bajo el marco de la teoria social cognitiva, el concepto de valores culturales de
      Leininger y el proceso de la sustraccion teorica, se desarrollo este articulo. Se
      muestran las relaciones del modelo con las proposiciones y los factores que
      influyen en el uso del condon para este grupo especifico. Finalmente, el modelo
      explica las variables de interes, los niveles de abstraccion y las relaciones
      entre si en el contexto nahuatl. El siguiente paso sera implementar los
      indicadores empiricos para conocer el grado de influencia de los factores
      personales y ambientales hacia el uso del condon en adolescentes nahuas.
      Resultados que aportaran informacion para el desarrollo del conocimiento en
      enfermeria y la reduccion de riesgo sexual de esta poblacion.

PMID- 29471684
TI  - The future role of proteomics in the understanding of acute kidney injury.

PMID- 29471685
TI  - Bronchial thermoplasty as a treatment for severe asthma: controversies, progress
      and uncertainties.
AB  - INTRODUCTION: Bronchial thermoplasty is a licensed non-pharmacological treatment
      for severe asthma. Area covered: This article considers evidence for the efficacy
      and safety of bronchial thermoplasty from clinical trials and observational
      studies in clinical practice. Its place in the management of severe asthma,
      predictors of response and mechanisms of action are reviewed. Expert commentary:
      Bronchial thermoplasty improves quality of life and reduces exacerbations in
      moderate to severe asthma. Morbidity from asthma is increased during treatment.
      Overall, patients treated in clinical practice have worse baseline
      characteristics and comparable clinical outcomes to trial data. Follow-up studies
      provide reassurance on long-term safety. Despite some progress, future research
      needs to investigate uncertainties about predictors of response, mechanism of
      action and place in management of asthma.

PMID- 29471686
TI  - Comparison of HbA1c and glycated albumin as a control marker for newborn
      complications in diabetic women in a multicentre study in Japan (Japan glycated
      albumin study group: study 2).
AB  - Background To clarify the relationship between glycated haemoglobin and glycated
      albumin concentrations during pregnancy with neonatal outcomes, a multicentre
      study was conducted by the Japanese Society of Diabetes and Pregnancy. Methods A
      total of 136 patients (type 1: n = 47, type 2: n = 89) who enrolled in the study
      were diagnosed based on the Japanese Diabetes Society diagnostic criteria for
      diabetes mellitus. Thresholds for glycated haemoglobin and glycated albumin were
      set at 5.8% and 15.8%, respectively, as the upper limits of the reference
      interval in pregnant women. Result Random plasma glucose decreased linearly, and
      reached the reference interval at 40 weeks. Glycated albumin concentrations also
      decreased in the same manner. But glycated haemoglobin concentrations were out of
      the reference interval during the study. The frequency of the neonatal
      complications did not show significant differences between the glycated
      haemoglobin ?5.8% group and the glycated haemoglobin <5.8% group. On the other
      hand, the frequency of neonatal complications showed higher tendency of neonatal
      complications in the incidence of polycythaemia ( P = 0.094) and heavy-for-date (
      P = 0.071) in the glycated albumin ?15.8% group compared with the glycated
      albumin <15.8 group. The respiratory disorder in type 1 diabetes was
      significantly higher than type 2 diabetes. Conclusions For the treatment of
      pregnant women with diabetes, glycated albumin would be a better marker than
      glycated haemoglobin. However, glycated albumin is also affected by obesity and
      albumin, and it is desirable to make a comprehensive judgment with glycated
      haemoglobin, random plasma glucose and other glycaemic index.

PMID- 29471687
TI  - Neutrophil CD64 - A potential biomarker in patients with complicated intra
      abdominal infections? - A literature review.
AB  - Complicated intra-abdominal infections (cIaIs) respresent a serious cause of
      morbidity and mortality. Early diagnosis and well-timed treatment can improve
      patients' outcome, whereas the delay in management often result in rapid
      progression to circulatory collapse, multiple organ failure, and death.
      Neutrophil CD64 antigen expression has been studied for several years as
      infectious and sepsis biomarker and has several characteristics that make it good
      for clinical employment. It has been suggested to be predictive of positive
      bacterial cultures and a useful test for management of sepsis and other
      significant bacterial infections. Our review concluded that the neutrophil CD64
      expression could be a promising and meaningful biomarker in patients with cIaIs.
      It shows good potential for evaluating the severity of the disease and could give
      information about the outcome. However, more large studies should be performed
      before using it in clinical practice.

PMID- 29471688
TI  - Plasmid-mediated quinolone resistance determinants in Enterobacteriaceae from
      urine clinical samples.
AB  - Plasmid-mediated quinolone resistance (PMQR) determinants including, qnrA, qnrB,
      qnrC, qnrD, qnrS, aac(6')-Ib-cr, oqxAB, and qepA, were investigated in 214
      Enterobacteriaceae strains from urine clinical samples. Antimicrobial
      susceptibility testing for ciprofloxacin, ceftriaxone, and imipenem was performed
      by broth microdilution method. All strains were screened for PMQR genes by PCR.
      Virulence determinants, namely afa, pap, pil, sfa/foc, and kpsMT of eight
      Escherichia coli strains proven positive for at least one qnr gene, were
      investigated by PCR. All of the eight investigated strains carried the pil gene,
      showing that P fimbria is a common virulence determinant among qnr positive E.
      coli. Out of 214 tested strains, 38 yielded any PMQR determinant, altogether 45
      genes were detected namely, 6 qnrA, 1 qnrB, 2 qnrD and 8 qnrS, 9 aac(6')-Ib-cr,
      and 19 oqxAB; however, neither qepA nor qnrC were detected. Notably, 18
      Klebsiella spp., harbored oqxAB, nine E. coli were positive for qnrS and two
      Morganella morganii yielded qnrD resistance determinant. In this study, we
      demonstrated 17.7% prevalence of PMQR-positive Enterobacteriaceae and first
      reported qnrD-resistance determinant in Hungary. Altogether, 25 PMQR-positive
      strains were susceptible or low-level resistant to ciprofloxacin with minimum
      inhibitory concentration (MIC) between 0.06 and 1 mg/L, suggesting that
      prevalence of PMQR determinants is underestimated and screening among clinical
      isolates exhibiting reduced susceptibility is necessary. Fluoroquinolone
      resistance breakpoints of Enterobacteriaceae were revised in 2017 by European
      Committee of Antimicrobial Susceptibility Testing indicating ciprofloxacin
      susceptibility only until 0.25 mg/L MIC value.

PMID- 29471689
TI  - Mediation of inflammatory ascites formation induced by macromolecules in mice.
AB  - The first 60-min phase of inflammatory ascites formation was studied by
      intraperitoneally (i.p.) administered macromolecular inducers: yeast cell wall
      zymosan binds to specific macrophage receptors, polyethyleneimine (PEI) and
      concanavalin A (ConA), produces non-covalent cross-links on the surface of
      various cells, while lambda-carrageenan may function as a contact activator.
      Depletion of peritoneal macrophages was performed by overnight pretreatment with
      diphtheria toxin in transgenic mice, resulting in a significant (p < 0.01)
      decrease in the induced formation of ascitic fluid. It was shown that induced
      ascites is mediated partly (PEI, ConA, and carrageenan) or completely (zymosan)
      by peritoneal macrophages. Inhibition of prostanoid synthesis with indomethacine
      or of the kallikrein/bradykinin system with aprotinin also produced a significant
      (p < 0.01) but incomplete inhibition. A slight additivity occurred between the
      different inhibitory effects. In another series of experiments, the i.p.
      administration of bradykinin (without a macromolecular inducer) also produced
      marked ascites, which was not affected by macrophage depletion. The origin of the
      macrophage-independent part of the induced ascites is best explained by the
      deformation of the mesothelial cell surface, resulting in signal transfer to the
      underlying endothelium and the passage of ascitic fluid in the opposite
      direction. The soluble mediators are represented by prostanoids, bradykinin and
      other, unidentified agonists.

PMID- 29471690
TI  - Genetic support of carbapenemases in double carbapenemase producer Klebsiella
      pneumoniae isolated in the Arabian Peninsula.
AB  - Enterobacteriaceae co-producing NDM- and OXA-48-type carbapenemases were
      encountered in higher frequency in the United Arab Emirates (UAE) than in the
      neighboring countries in our earlier study. The aim of this investigation was to
      characterize the seven double carbapenemase producer Klebsiella pneumoniae found
      in the region to assess factors contributing to their emergence. Three K.
      pneumoniae ST14 isolated in the UAE harboring blaNDM-1 on IncHI1b and blaOXA-232
      on IncColE plasmids were clonally related. Furthermore, two K. pneumoniae from
      the UAE, ABC106 and ABC137 belonged to ST307 and ST1318, respectively. ABC106
      carried blaNDM-1 on IncHI1b, and blaOXA-162 on IncL/M plasmids, whereas ABC137
      possessed blaNDM-1 on IncX3 and blaOXA-48 on IncL/M plasmids. The double
      carbapenemase-producing K. pneumoniae from Oman (OMABC109) and Saudi Arabia
      (SA54) belonged to ST11 and ST152, respectively. OMABC109 harbored blaNDM-1 on an
      IncHI1b plasmid highly similar to the NDM-plasmid of ABC106 and carried a
      chromosomally coded blaOXA-181 located on Tn2013. SA54 possessed a blaNDM-1 on an
      IncFIb/FII plasmid and a blaOXA-48 on an IncL/M plasmid. Based on these findings,
      clonal spread and horizontal transfer of carbapenemase genes located on
      transposons or self-transmissible plasmids contributed equally to the emergence
      of double carbapenemase-producing Enterobacteriaceae in the region.

PMID- 29471691
TI  - Streptococcus pneumoniae quorum sensing and biofilm formation are affected by
      Thymus daenensis, Satureja hortensis, and Origanum vulgare essential oils.
AB  - The aim of this study was to investigate the effect of Thymus daenensis L.,
      Satureja hortensis L., and Origanum vulgare L. essential oils (EOs) on the
      planktonic growth, biofilm formation, quorum sensing (QS), and competence system
      (CS) of Streptococcus pneumoniae. The anti-biofilm activity of EOs was determined
      by Microtiter-Plate Test (MtP) and scanning electron microscope (SEM). The QS and
      CS inhibitory activities were determined on the pre-grown biofilm by gene
      expression analysis using quantitative real-time RT-PCR. Using gas chromatography
      mass spectrometry analysis, the major components of the tested EOs were detected.
      The MtP and SEM detected a significant inhibitory effect of the three EOs on
      biofilm formation at sub-minimum inhibitory concentrations (MICs). The most anti
      biofilm activity was seen for T. daenensis. LuxS and pfs genes (genes involved in
      QS) downregulated the following treatment with MIC/2 of Thymus and Satureja EOs.
      Thymol, carvacrol, p-cymene, pulegone, and 1,8-cineole were the major components
      of the tested EOs. The used EOs seem to be good candidates for preventing biofilm
      formation and subsequent colonization of S. pneumoniae. This study introduced T.
      daenensis and S. hortensis as new anti-biofilm and QS inhibitor agents with a
      natural origin.

PMID- 29471692
TI  - Bacterial diversity in soils of different Hungarian karst areas.
AB  - Karst areas have great environmental importance as sources of subsurface water
      and often maintain very sensitive ecosystems. In recent years, increasing number
      of microbiological studies focused on the bacterial communities of karst soils.
      In this study, diversity examinations on two distinct Hungarian karst areas,
      Aggtelek and Tapolca, were performed using parallel cultivation and molecular
      cloning methods. The phylogenetic affiliation of bacterial strains and molecular
      clones was determined based on their 16S rRNA gene sequences. Bacterial isolates
      were identified as members of the phyla Actinobacteria, Firmicutes,
      Proteobacteria, and Bacteroidetes. Besides the taxa identified by cultivation,
      members of the phyla Chloroflexi, Cyanobacteria, Acidobacteria, Verrucomicrobia,
      and Gemmatimonadetes were detected by the cloning. The difference in the
      composition of soil bacterial communities was related to geographic locations and
      soil types. Both the highest and the lowest bacterial diversities were detected
      in samples from Aggtelek National Park, characterized by Leptic Luvisol and
      Rendzic Leptosol soil types. The difference in the composition of bacterial
      communities between Rendzic Leptosol and Leptic Phaeozem soil types at Tapolca
      could be the result of human impacts.

PMID- 29471693
TI  - Study of MazEF, sam, and phd-doc putative toxin-antitoxin systems in
      Staphylococcus epidermidis.
AB  - Today, to replace the antibacterial targets to overcome antibiotic resistance,
      toxin-antitoxin (TA) system is noticeable, where the unstable antitoxin
      neutralizes the stable toxin and protects the bacteria against the toxic effects.
      The presence and expression of TA genes in clinical and non-clinical strains of
      Staphylococcus epidermidis were investigated in this study. After identification
      of three TA pairs (mazEF, sam, and phd-doc) via existing databases (earlier,
      there has been no information in the case of S. epidermidis isolates), the
      presence and expression of these pairs were investigated by PCR and q-PCR,
      respectively. We detected three TA modules in all antibiotic sensitive and
      resistant isolates. In addition, q-PCR analysis revealed that the transcripts
      were produced from the three TA modules. This study showed the significant
      prevalence of these systems in pathogenic bacteria and they were equally found in
      both oxacillin-resistant and oxacillin-susceptible bacteria. The high prevalence
      of three systems can make them suitable as potential targets for antibiotic
      therapy.

PMID- 29471694
TI  - Assessing the microbial communities inhabiting drinking water networks and
      nitrifying enrichments with special respect on nitrifying microorganisms.
AB  - This study provides a comprehensive microbiological survey of three drinking
      water networks applying different water treatment processes. Variability of
      microbial communities was assessed by cultivation-based [nitrifying, denitrifying
      most probable number (MPN) heterotrophic plate count] and sequence-aided terminal
      restriction fragment length polymorphism (T-RFLP) analysis. The effect of
      microbial community composition on nitrifying MPN values was revealed. The non
      treated well water samples showed remarkable differences to their corresponding
      distribution systems regarding low plate count, nitrifying MPN, and the
      composition of microbial communities, which increased and changed, respectively,
      in distribution systems. Environmental factors, such as pH, total inorganic
      nitrogen content (ammonium and nitrite concentration), and chlorine dioxide
      treatment had effect on microbial community compositions. The revealed
      heterogeneous nitrifying population achieved remarkable nitrification, which
      occurred at low ammonium concentration (14-51 MUM) and slightly alkaline pH 7.7
      7.9 in chlorine dioxide disinfected water networks. No change was observed in
      nitrification-generated nitrate concentration, although nitrate-reducing (and
      denitrifying) bacteria were present with low MPN and characterized by sequence
      aided T-RFLP. The community structures of water samples partially changed in
      nitrifying enrichments and had influence on the generated nitrifying, especially
      nitrite-oxidizing MPN regarding the facilitated growth of nitrate-reducing
      bacteria and even methanogenic archaea beside ammonia-oxidizing microorganisms
      and nitrite-oxidizing bacteria.

PMID- 29471695
TI  - A rarely isolated Gram-negative bacterium in microbiology laboratories: Leclercia
      adecarboxylata ?.

PMID- 29471696
TI  - The recombinant fusion protein CFP10-ESAT6-dIFN has protective effect against
      tuberculosis in guinea pigs.
AB  - Development of effective vaccine candidates against tuberculosis is currently the
      most important challenge in the prevention of this disease since the BCG vaccine
      fails to guarantee a lifelong protection, while any other approved vaccine with
      better efficiency is still absent. The protective effect of the recombinant
      fusion protein ESAT6-CFP10-dIFN produced in a prokaryotic expression system
      (Escherichia coli) has been assessed in a guinea pig model of acute tuberculosis.
      The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6
      and CFP10 as well as modified human gamma-interferon (dIFN) for boosting the
      immune response. Double intradermal immunization of animals with the tested
      fusion protein (2 * 0.5 MUg) induces a protective effect against subsequent Mtb
      infection. The immunized animals do not develop the symptoms of acute
      tuberculosis and their body weight gain was five times more as compared with the
      non-immunized-infected animals. The animal group immunized with this dose of
      antigen displays the minimum morphological changes in the internal organs and
      insignificant inflammatory lesions in the liver tissue, which complies with a
      decrease in the bacterial load in the spleen and average Mtb counts in
      macrophages.

PMID- 29471697
TI  - First report of Acanthamoeba genotype T8 human keratitis.
AB  - Acanthamoeba has a worldwide distribution in the environment and it is capable of
      causing a painful sight-threatening disease of the cornea designated as
      Acanthamoeba keratitis (AK). Nowadays, the cases of AK have surged all over the
      world along with its disease burden due to increasing use of contact lenses used
      not only for optical correction but also for cosmetic purposes. In our present
      work, epithelial abrasion of a 27-year-old female soft contact lens wearer with
      keratitis was examined. Genotype identification was carried out with a real-time
      fluorescence resonance energy transfer polymerase chain reaction (PCR) assay
      based on sequence analysis of the 18S rRNA gene. Genotyping allowed the
      identification of a T8 group isolate. The analysis confirmed the importance of a
      complete diagnostic protocol, including a PCR assay, for the clinical diagnosis
      of AK from human samples. Acanthamoeba T8 should be considered as potential
      causative organism in keratitis in human.

PMID- 29471698
TI  - Gender differences in acute coronary syndromes: focus on the women with ACS
      without an obstructing culprit lesion.
AB  - INTRODUCTION: The etiologies of acute coronary syndromes (ACS) in women expand
      beyond the traditional paradigm of obstructive epicardial atherosclerotic disease
      and plaque rupture. Fundamental differences in pathobiology and presentation can
      partially explain the gender disparity in ACS diagnosis and management, but there
      is also much we do not know about the spectrum of coronary artery disease in
      women. Areas covered: This review seeks to explain some key differences between
      men and women in terms of risk factors, pathophysiology, and clinical
      presentations, as well as identify areas where more data are needed, focusing on
      women presenting with ACS but without a culprit lesion to explain their
      presentation. Literature search was undertaken with PubMed and Google Scholar.
      Expert commentary: Women with acute coronary syndromes but without plaque rupture
      or obstructive epicardial atherosclerosis can be difficult to diagnose and
      manage. Improving care in this underdiagnosed and undertreated population will
      require early identification of at risk patients, development of better
      diagnostic strategies, and standardized implementation of guideline-based
      therapies.

PMID- 29471699
TI  - Atezolizumab for the treatment of colorectal cancer: the latest evidence and
      clinical potential.
AB  - INTRODUCTION: Atezolizumab is a fully humanized, engineered monoclonal antibody
      that specifically targets PD-L1, key molecule in the cancer-immunity pathway.
      Atezolizumab is currently approved for the treatment of metastatic non-small-cell
      lung cancer and advanced urothelial carcinomas. Areas covered: In this review, we
      will present the available data supporting the efficacy of atezolizumab for the
      treatment of metastatic colorectal cancer (mCRC). We will also provide an update
      on the ongoing/future clinical trials evaluating the role of atezolizumab for the
      treatment of CRC in different settings (alone or in combination with other
      checkpoint inhibitors and/or targeted therapies). So far, a small subgroup of
      mCRC (those with deficiency in mismatch repair - dMMR) appears to benefit
      significantly from checkpoint inhibitors. As expected, further research is needed
      to develop biomarkers, effective therapeutic strategies and novel combinations to
      overcome immune escape resistance and achieve better responses with minimal
      toxicities. Expert opinion: Interim analyses from ongoing early-phase studies in
      mCRC have shown encouraging activity of atezolizumab in combination with
      chemotherapy and/or targeted therapies, especially with MEK inhibitor
      cobimetinib. Within the next few years, this PD-L1 checkpoint inhibitor will
      likely be included as one of the treatment options for CRC, at least for patients
      with dMMR.

PMID- 29471700
TI  - Methodological concerns with the meta-analysis comparing insulin
      degludec/liraglutide and insulin glargine/lixisenatide.

PMID- 29471701
TI  - Repairing the corneal epithelium using limbal stem cells or alternative cell
      based therapies.
AB  - INTRODUCTION: The corneal epithelium is maintained by limbal stem cells (LSCs)
      that reside in the basal epithelial layer of the tissue surrounding the cornea
      termed the limbus. Loss of LSCs results in limbal stem cell deficiency (LSCD)
      that can cause severe visual impairment. Patients with partial LSCD may respond
      to conservative therapies designed to rehabilitate the remaining LSCs. However,
      if these conservative approaches fail or, if complete loss of LSCs occurs,
      transplantation of LSCs or their alternatives is the only option. While a number
      of clinical studies utilizing diverse surgical and cell culture techniques have
      shown favorable results, a universal cure for LSCD is still not available.
      Knowledge of the potential risks and benefits of current approaches, and
      development of new technologies, is essential for further improvement of LSCD
      therapies. Areas covered: This review focuses on cell-based LSCD treatment
      approaches ranging from current available clinical therapies to preclinical
      studies of novel promising applications. Expert opinion: Improved understanding
      of LSC identity and development of LSC expansion methods will influence the
      evolution of successful LSCD therapies. Ultimately, future controlled clinical
      studies enabling direct comparison of the diverse employed approaches will help
      to identify the most effective treatment strategies.

PMID- 29471702
TI  - Children With ADHD Symptoms: Who Can Do Without Specialized Mental Health Care?
AB  - OBJECTIVE: A new Dutch Child and Youth Act should reduce specialized mental
      health care for children with symptoms of ADHD. Characteristics of children
      referred to a specialized ADHD clinic are explored to give direction to this
      intention. METHOD: Data of 261 children who underwent a multidisciplinary best
      practice evaluation (including rating scales, and demographic, psychological, and
      somatic findings) were analyzed. Univariable and multivariable logistic
      regression models were used to find predictive variables for the need of
      specialized mental health care. RESULTS: Collected data were heterogeneous.
      (Sub)clinical total scores on the Teacher Report Form (TRF) and Child Behavior
      Checklist (CBCL) were predictive variables for specialized mental health care.
      Also children with divorced parents were more often referred to specialized care.
      CONCLUSION: (Sub)clinical scores on the CBCL and TRF increased the need for
      specialized care, but comprehensive assessment of every child with ADHD symptoms
      was necessary to differentiate between levels of care.

PMID- 29471703
TI  - Maternal second trimester blood levels of selected heavy metals in pregnancies
      complicated with neural tube defects.
AB  - PURPOSE: Neural tube defects (NTDs) are the most common malformations of the
      central nervous system (CNS). There is continuing research for the identification
      of risk factors and interventions for prevention of NTDs. The aim of this study
      was to investigate the maternal second trimester blood levels of selected heavy
      metals namely, arsenic (As), cadmium (Cd), mercury (Hg), manganese (Mn), nickel
      (Ni), and lead (Pb) and their possible relation with the occurrence of NTDs.
      METHODS: Twenty-one healthy second trimester pregnant women with fetuses affected
      with NTD (cases) were matched with 21 healthy pregnant women with unaffected
      fetuses (controls) with respect to age, body mass index (BMI), and gestational
      age. Maternal blood levels of heavy metals were measured after an overnight
      fasting period. RESULTS: No significant differences were observed in terms of
      maternal blood levels of As, Cd, Hg, and Ni between NTD-affected and unaffected
      pregnancies. The blood Pb and Mn levels were found to be higher in pregnant women
      with a fetus affected with NTD when compared with pregnant women with unaffected
      fetuses (for Pb, in cases 12.3 +/- 5.5 ug/L, in controls 7.8 +/- 2.4 ug/L; for Mn
      in cases 3.6 +/- 1.4 ug/L, in controls 2.4 +/- 1.0 ug/L, p < .05). CONCLUSIONS:
      High maternal second trimester blood levels of Pb and Mn during pregnancy are
      associated with NTDs in the newborn.

PMID- 29471704
TI  - Flow-diverter stents for endovascular management of non-fetal posterior
      communicating artery aneurysms-analysis on aneurysm occlusion, vessel patency,
      and patient outcome.
AB  - Background Use of flow-diversion technology in the treatment of incidental and
      recanalized posterior communicating artery (PComA) aneurysms. Methods Patients
      treated with the Pipeline embolization device (PED) for PComA aneurysms were
      identified and included in our retrospective analysis. We evaluated aneurysm
      characteristics, modified Rankin Scale score (mRS) on admission, angiography
      follow-up, and patient clinical outcome at discharge, at three to nine months,
      and at 12-18 months. Results We included 56 patients with a mean age of 56 years.
      Median mRS on admission was 0. All aneurysms involved the PComA and were either
      new findings or found to have shown recanalization at angiography follow-up from
      previous coil embolization or surgical clipping. Intraprocedural device
      foreshortening was observed in one case requiring additional placement of a self
      expanding stent. One intraprocedural aneurysm rupture occurred because of a
      broken distal wire. This patient had an mRS of 4 after the procedure. Three- to
      nine-month and 12- to 18-month follow-up angiography showed near complete or
      complete aneurysm occlusion in most cases. Minimal to mild intimal hyperplasia
      was seen in five cases at three to nine months. PComA patency over time showed 29
      of 46 initially patent vessels still patent at six months. Thirteen and seven
      PComAs showed progressive decrease in flow at three to nine months and 12-18
      months, respectively. Median mRS remained 0 for all patients at three- to nine
      month and 12- to 18-month follow-up. Conclusions Our preliminary results show
      that flow-diversion technology is an effective and safe treatment option. Larger
      studies with long-term follow-up are needed to validate our promising results.

PMID- 29471705
TI  - Differences in outcomes between cesarean section in the second versus the first
      stages of labor.
AB  - OBJECTIVE: We aimed to compare maternal morbidity and mortality of cesarean
      sections (CS) in the second versus first stage of labor. STUDY DESIGN:
      Retrospective study of all CS at a single, university-affiliated medical center,
      between January 2010 and December 2014. Eligibility was limited to term,
      singleton pregnancies with cephalic presentation. Maternal outcomes of second
      stage CS were compared to those of first-stage CS. The primary outcome was
      defined as estimated blood loss >1000 ml. RESULTS: Overall, 1004 women met the
      inclusion criteria, of which 290 (29%) had a second-stage CS and 714 (71%) had a
      first-stage CS. Women in the second-stage CS group had a higher nulliparity and
      hypertensive disorders rates and a lower rate of previous CS. Second-stage CS was
      associated with more than double the rate of estimated blood loss >1000 ml (9.7%
      versus 3.8%, p<.001), and more prone to unintentional uterine incision extension,
      uterine atony, hemoglobin decrease >2 g/l and antibiotic treatment for suspected
      endometritis. In a multivariable logistic regression model, second-stage CS was
      found to be independently associated with unintentional uterine incision
      extension (OR 6.8, 95% CI 4.1-11.2), uterine atony (OR 3.3, 95% CI 1.4-8.0) and
      antibiotic treatment for suspected endometritis (OR 2.6, 95% CI 1.4-5.1), but not
      with excessive blood loss (OR 1.5, 95% CI 0.8-2.8). Additionally, failed assisted
      vaginal delivery prior to second-stage CS was not associated with a higher rate
      of complications. CONCLUSION: Second-stage CS is associated with higher rates of
      adverse maternal outcomes, mainly unintentional uterine incision extension,
      uterine atony, and suspected endometritis.

PMID- 29471707
TI  - Delivery during extracorporeal membrane oxygenation (ECMO) support of pregnant
      woman with severe respiratory distress syndrome caused by influenza: a case
      report and review of the literature.
AB  - OBJECTIVE: To report a case of labour induction during extracorporeal membrane
      oxygenation (ECMO) support in a patient with acute respiratory distress syndrome
      (ARDS) caused by influenza and review of the literature. METHODS: Case report and
      the literature search of all English articles on delivery while on ECMO in
      patients with ARDS caused by influenza. RESULTS: A 25-year-old pregnant woman was
      initiated with ECMO due to severe ARDS caused by influenza A (H1N1) virus. When
      the patient had symptoms of colporrhagia and uterine contractions, the medical
      team decided to start labour induction while on ECMO. There were in total five
      case reports identified. Maternal oxygenation was improved after delivery and
      ECMO was successfully discontinued. CONCLUSIONS: Maternal oxygenation was
      improved after delivery, which may be beneficial to reduce the duration of ECMO.
      Caesarean section (CS) may be the most used mode and labour induction could be
      another option. The procedure should be performed by an experienced ECMO team,
      cooperating with the obstetrician, anaesthesiologist, and ICU doctors.

PMID- 29471706
TI  - "Where Did This [PrEP] Come From?" African American Mother/Daughter Perceptions
      Related to Adolescent Preexposure Prophylaxis (PrEP) Utilization and Clinical
      Trial Participation.
AB  - Despite the demonstrated effectiveness of preexposure prophylaxis (PrEP) to
      reduce incident HIV infections, PrEP's potential as an HIV prevention strategy
      for adolescent populations is unknown. This study assessed perceptions of
      adolescent PrEP use and clinical trial participation among African American women
      and their adolescent daughters. We conducted focus group discussions with 15
      African American mother/daughter pairs ( N = 30). Findings suggest a general lack
      of PrEP awareness, favorable attitudes toward adolescent PrEP use, altruistic
      attitudes regarding research participation among daughters, and less favorable
      attitudes toward adolescent clinical trial participation among mothers. Study
      findings have the potential to inform strategies that provide equitable access to
      HIV scientific advances among African American women and girls and promote
      informed parent-child research decision making.

PMID- 29471708
TI  - Visual attention mechanisms in happiness versus trustworthiness processing of
      facial expressions.
AB  - A happy facial expression makes a person look (more) trustworthy. Do perceptions
      of happiness and trustworthiness rely on the same face regions and visual
      attention processes? In an eye-tracking study, eye movements and fixations were
      recorded while participants judged the un/happiness or the un/trustworthiness of
      dynamic facial expressions in which the eyes and/or the mouth unfolded from
      neutral to happy or vice versa. A smiling mouth and happy eyes enhanced perceived
      happiness and trustworthiness similarly, with a greater contribution of the smile
      relative to the eyes. This comparable judgement output for happiness and
      trustworthiness was reached through shared as well as distinct attentional
      mechanisms: (a) entry times and (b) initial fixation thresholds for each face
      region were equivalent for both judgements, thereby revealing the same
      attentional orienting in happiness and trustworthiness processing. However, (c)
      greater and (d) longer fixation density for the mouth region in the happiness
      task, and for the eye region in the trustworthiness task, demonstrated different
      selective attentional engagement. Relatedly, (e) mean fixation duration across
      face regions was longer in the trustworthiness task, thus showing increased
      attentional intensity or processing effort.

PMID- 29471709
TI  - Trilinguals' language switching: A strategic and flexible account.
AB  - The goal of this study was to determine how trilinguals select the language they
      intend to use in a language switching context. Two accounts are examined: (a) a
      language-specific account, according to which language selection considers the
      activation level of words of the intended language only (i.e., language co
      activation without language competition), and (b) a language non-specific
      account, where activated words from both the intended and non-intended languages
      compete for selection (i.e., language co-activation with language competition).
      Results showed that, in both groups, all three languages competed for selection
      and that selection was achieved by inhibiting the currently non-relevant
      languages. Moreover, extending findings from previous research, the study reveals
      that, in both Experiments 1 and 2, the amount of inhibition was influenced not
      only by language proficiency but also by the typological similarity between
      languages. Overall, the study shows that language switching performance can be
      accounted for by a strategic and flexible inhibitory account. In particular, the
      controlling system is "strategic" in the sense that it aims at preventing
      potential conflicting situations, such as typological closeness between
      languages, and it is "flexible" in that it adjusts languages' activation levels,
      depending on the conflict to be solved.

PMID- 29471710
TI  - Predicting our own and others' future preferences: The role of social distance.
AB  - People underestimate how much their preferences will change in the future, a
      phenomenon sometimes referred to as a "presentism bias." Recently, we found that
      this presentism bias is attenuated when thinking about the preferences of other
      people. The aim of this study was to investigate whether predicting future
      preferences also differs depending on the level of social distance between self
      and other. A total of 67 participants completed a perspective-taking task in
      which they were required to think about their own preferences, those of a generic
      peer, and those of a close other both now and in the future. They were also asked
      to consider the preferences of an older adult now. Participants predicted less
      change between their current and future preferences than between the current and
      future preferences of a generic peer. Predicted change in preferences for a close
      other were similar, but not identical, to those made for the self. When
      considering relevant future preferences, participants predicted less change for
      themselves than for their close others and less change for close others than for
      generic peers. In other words, as social distance increases, the presentism bias
      decreases. Interestingly, participants estimated that both they and their peers
      would not change so much that they become similar to current older adults.
      Simulating the future perspectives of a generic peer or, even better, the current
      perspectives of an older adult may thus result in improved long-term decision
      making, as it may enable a more realistic estimation of the magnitude of likely
      changes in the future.

PMID- 29471711
TI  - Enhancing Autonomy in Biobank Decisions: Too Much of a Good Thing?
AB  - The opportunity to receive individual research results (IRRs) in accordance with
      personal preferences may incentivize biobank participation and maximize perceived
      benefit. This trial investigated the relationship between parents' preferences
      and intent to participate (ITP) in biobank research utilizing their child's
      genetic information. We randomized parents of pediatric patients to four
      hypothetical biobanks, one of which employed a preference-setting model for
      return of results regarding their child. ITP was highest among those desiring all
      types of IRRs (93.3%) and decreased as participants became increasingly selective
      with their preferences ( p < .0001). We demonstrated that most parents would
      participate in a biobank that allows for preference setting; however, those who
      set preferences to receive a narrower set of IRRs are less likely to participate.

PMID- 29471712
TI  - Memory and conceptual learning of relevant and non-relevant items in item-method
      directed forgetting.
AB  - The present research investigates the fate of non-target information when people
      are trying to either intentionally memorise or forget target information. By
      using an object-based attentional manipulation within a directed forgetting
      paradigm (item-method), we show a directed forgetting effect (DFE, i.e., better
      memory for to-be-remembered (TBR) than for to-be-forgotten (TBF) items) for items
      that participants are explicitly instructed to attend but not for irrelevant
      items that happen to be part of the context. Alongside the classic DFE, we
      investigate how the category of the attended and unattended items are learned.
      The results obtained in three experiments, show that people can successfully
      learn only the category of the TBR attended items and that the DFE extends to new
      items that are related to the old TBR and TBF items (an effect that we call
      conceptual DFE). These results give us new insight about how TBR and TBF items
      are processed and conceptually learned.

PMID- 29471713
TI  - Silk fibroin/chitosan thin film promotes osteogenic and adipogenic
      differentiation of rat bone marrow-derived mesenchymal stem cells.
AB  - As a biodegradable polymer thin film, silk fibroin/chitosan composite film
      overcomes the defects of pure silk fibroin and chitosan films, respectively, and
      shows remarkable biocompatibility, appropriate hydrophilicity and mechanical
      properties. Silk fibroin/chitosan thin film can be used not only as metal implant
      coating for bone injury repair, but also as tissue engineering scaffold for skin,
      cornea, adipose, and other soft tissue injury repair. However, the
      biocompatibility of silk fibroin/chitosan thin film for mesenchymal stem cells, a
      kind of important seed cell of tissue engineering and regenerative medicine, is
      rarely reported. In this study, silk fibroin/chitosan film was prepared by
      solvent casting method, and the rat bone marrow-derived mesenchymal stem cells
      were cultured on the silk fibroin/chitosan thin film. Osteogenic and adipogenic
      differentiation of rat bone marrow-derived mesenchymal stem cells were induced,
      respectively. The proliferation ability, osteogenic and adipogenic
      differentiation abilities of rat bone marrow-derived mesenchymal stem cells were
      systematically compared between silk fibroin/chitosan thin film and polystyrene
      tissue culture plates. The results showed that silk fibroin/chitosan thin film
      not only provided a comparable environment for the growth and proliferation of
      rat bone marrow-derived mesenchymal stem cells but also promoted their osteogenic
      and adipogenic differentiation. This work provided information of rat bone marrow
      derived mesenchymal stem cells behavior on silk fibroin/chitosan thin film and
      extended the application of silk fibroin/chitosan thin film. Based on the
      results, we suggested that the silk fibroin/chitosan thin film could be a
      promising material for tissue engineering of bone, cartilage, adipose, and skin.

PMID- 29471714
TI  - The Bodily Illusion in Adverse Conditions: Virtual Arm Ownership During
      Visuomotor Mismatch.
AB  - Classically, body ownership illusions are triggered by cross-modal synchronous
      stimulations, and hampered by multisensory inconsistencies. Nonetheless, the
      boundaries of such illusions have been proven to be highly plastic. In this
      immersive virtual reality study, we explored whether it is possible to induce a
      sense of body ownership over a virtual body part during visuomotor
      inconsistencies, with or without the aid of concomitant visuo-tactile
      stimulations. From a first-person perspective, participants watched a virtual
      tube moving or an avatar's arm moving, with or without concomitant synchronous
      visuo-tactile stimulations on their hand. Three different virtual arm/tube speeds
      were also investigated, while all participants kept their real arms still. The
      subjective reports show that synchronous visuo-tactile stimulations effectively
      counteract the effect of visuomotor inconsistencies, but at slow arm movements, a
      feeling of body ownership might be successfully induced even without concomitant
      multisensory correspondences. Possible therapeutical implications of these
      findings are discussed.

PMID- 29471715
TI  - The effect of acute dissociation on the electrophysiological properties of rat
      dorsal root ganglion neurons.
AB  - The acutely dissociated neurons from the dorsal root ganglia (DRGs) are
      extensively used. The effects of acute dissociation on the properties of these
      neurons are, however, not clear. In this study, the action potentials (APs) were
      recorded from both acutely dissociated and in vivo identified DRG neurons with
      patch clamp and sharp electrode recording techniques, respectively. We found that
      acute dissociation slowed both the depolarizing and repolarizing rate of APs, and
      elongated the AP duration (APD). The lower recording temperature presented in the
      acutely dissociated neurons contributed to about 10% of these differences. The
      major contributor of these differences was possibly modulation of the mRNA
      expression especially those of the ion channels, as suggested by our observation
      that acute dissociation significantly reduced the mRNA abundance of Nav1.6-1.9.
      In conclusion, acute dissociation altered the electrophysiological properties of
      the DRG neurons; the disrupted gene-expression pattern may contribute to this
      effect.

PMID- 29471716
TI  - Age-related differences in emotion matching are limited to low intensity
      expressions.
AB  - Multi-label tasks confound age differences in perceptual and cognitive processes.
      We examined age differences in emotion perception with a technique that did not
      require verbal labels. Participants matched the emotion expressed by a target to
      two comparison stimuli, one neutral and one emotional. Angry, disgusted, fearful,
      happy, and sad facial expressions of varying intensity were used. Although older
      adults took longer to respond than younger adults, younger adults only outmatched
      older adults for the lowest intensity disgust and fear expressions. Some
      participants also completed an identity matching task in which target stimuli
      were matched on personal identity instead of emotion. Although irrelevant to the
      judgment, expressed emotion still created interference. All participants were
      less accurate when the apparent difference in expressive intensity of the matched
      stimuli was large, suggesting that salient emotion cues increased difficulty of
      identity matching. Age differences in emotion perception were limited to very low
      intensity expressions.

PMID- 29471717
TI  - Differential Response in Novel Stem Cell Niches of the Brain after Cervical
      Spinal Cord Injury and Traumatic Brain Injury.
AB  - Populations of neural stem cells (NSCs) reside in a number of defined niches in
      the adult central nervous system (CNS) where they continually give rise to mature
      cell types throughout life, including newly born neurons. In addition to the
      prototypical niches of the subventricular zone (SVZ) and subgranular zone (SGZ)
      of the hippocampal dentate gyrus, novel stem cell niches that are also neurogenic
      have recently been identified in multiple midline structures, including
      circumventricular organs (CVOs) of the brain. These resident NSCs serve as a
      homeostatic source of new neurons and glial cells under intact physiological
      conditions. Importantly, they may also have the potential for reparative
      processes in pathological states such as traumatic spinal cord injury (SCI) and
      traumatic brain injury (TBI). As the response in these novel CVO stem cell niches
      has been characterized after stroke but not following SCI or TBI, we
      quantitatively assessed cell proliferation and the neuronal and glial lineage
      fate of resident NSCs in three CVO nuclei-area postrema (AP), median eminence
      (ME), and subfornical organ (SFO) -in rat models of cervical contusion-type SCI
      and controlled cortical impact (CCI)-induced TBI. Using bromodeoxyuridine (BrdU)
      labeling of proliferating cells, we find that TBI significantly enhanced
      proliferation in AP, ME, and SFO, whereas cervical SCI had no effects at early or
      chronic time-points post-injury. In addition, SCI did not alter NSC
      differentiation profile into doublecortin-positive neuroblasts, GFAP-expressing
      astrocytes, or Olig2-labeled cells of the oligodendrocyte lineage within AP, ME,
      or SFO at both time-points. In contrast, CCI induced a pronounced increase in
      Sox2- and doublecortin-labeled cells in the AP and Iba1-labeled microglia in the
      SFO. Lastly, plasma derived from CCI animals significantly increased NSC
      expansion in an in vitro neurosphere assay, whereas plasma from SCI animals did
      not exert such an effect, suggesting that signaling factors present in blood may
      be relevant to stimulating CVO niches after CNS injury and may explain the
      differential in vivo effects of SCI and TBI on the novel stem cell niches.

PMID- 29471719
TI  - An fMRI study of loneliness in younger and older adults.
AB  - Loneliness, the subjective experience of social isolation, may reflect, in part,
      underlying neural processing of social signals. Aging may exacerbate loneliness
      due to decreased social networks and increased social isolation, or it may reduce
      loneliness due to preferential attentional processing of positive information and
      increased interactions with emotionally close partners. Here, we conducted a
      functional magnetic resonance imaging (fMRI) study of loneliness in younger (N =
      50, 26 female, Mage = 20.4) and older (N = 49, 30 female, Mage = 62.9) adults.
      Compared to younger adults, older adults were less lonely and dwelled longer on
      faces, regardless of valence. Previous studies in younger adults found that
      loneliness was negatively correlated with ventral striatal (VS) activation to
      pleasant social pictures of strangers yet positively correlated with VS
      activation to faces of close others. In the present study, we observed no
      association between loneliness and VS activation to social pictures of strangers
      in either age group. Further, unlike previous studies, we observed no association
      between social network size and amygdala activation to social stimuli. Additional
      research is needed to examine the effect of loneliness and social network size on
      neural processing of different dimensions of social stimuli.

PMID- 29471720
TI  - Idols as Sunshine or Road Signs: Comparing Absorption-Addiction Idolatry With
      Identification-Emulation Idolatry.
AB  - This study seeks to contrast absorption-addiction idolatry and identification
      emulation idolatry. Whereas absorption-addiction idolatry progresses from
      entertainment/socializing to personalizing and obsession about the idol,
      identification-emulation idolatry unfolds in terms of identification, attachment,
      romantization, idealization, and consumption about the idol or his or her
      derivatives. Based on a sample of 1310 secondary school and university students
      in Hong Kong, the study verified the original factor model composed of five first
      order identification-emulation idolatry and three first-order absorption
      addiction idolatry factors, with the latter more predictable by fans' club
      membership.

PMID- 29471718
TI  - The VraSR regulatory system contributes to virulence in Streptococcus suis via
      resistance to innate immune defenses.
AB  - Streptococcus suis is a highly invasive pathogen that can cause sepsis and
      meningitis in pigs and humans. However, we have limited understanding of the
      mechanisms S. suis uses to evade innate immunity. To investigate the involvement
      of the two-component signal transduction system of S. suis in host immune
      defense, we examined the expression of 15 response regulators of S. suis
      following stimulation with polymorphonuclear leukocytes (PMNs). We found that
      several response regulators were significantly up-regulated including vraR. Thus,
      we constructed an isogenic deletion mutant of vraSR genes in S. suis and
      demonstrated VraSR promotes both bacterial survival in human blood and resistance
      to human PMN-mediated killing. The VraSR mutant was more susceptible to
      phagocytosis by human PMNs and had greater sensitivity to oxidant and lysozyme
      than wild-type S. suis. Furthermore, in vitro findings and in vivo evidence from
      a mouse infection model together strongly demonstrate that DeltavraSR had greatly
      attenuated virulence compared with wild-type S. suis. Collectively, our data
      reveal that VraSR is a critical regulatory system that contributes to the
      survival of S. suis and its ability to defend against host innate immunity.

PMID- 29471721
TI  - Evaluation of Epithelial Lining Fluid Concentration of Amikacin in Critically Ill
      Patients With Ventilator-Associated Pneumonia.
AB  - INTRODUCTION: Classically, aminoglycosides are known to have low penetration into
      the lung tissue. So far, no study has been conducted on human adult patients to
      evaluate amikacin concentration in epithelial lining fluid (ELF) of the alveoli.
      Therefore, convincing data are not available from the perspective of
      pharmacokinetics to support the fact that a dosage of 20 mg/kg of amikacin is
      sufficient to treat patients with ventilator-associated pneumonia (VAP). METHOD:
      This was a pilot study of amikacin concentration measurement in the alveolar site
      of action in critically ill adult patients with VAP who required aminoglycoside
      therapy. A dose of 20 mg/kg of amikacin was administered over a 30-minute
      infusion. The serum concentrations of amikacin were evaluated in the first,
      second, fourth, and sixth hours. However, the ELF concentration of amikacin was
      evaluated in the second hour with the help of bronchoalveolar lavage sampling
      technique. RESULTS: A total number of 8 patients was included in the study. The
      mean (SD) administered dose was 20 (0.9) mg/kg. The mean (SD) peak plasma
      concentration of amikacin was 59.6 (23) mg/L, with the volume of distribution of
      0.36 (0.13)L/kg. The amikacin concentration in ELF was successfully measured in 7
      patients (6.3) mg/L. The lung tissue penetration of the drug was described as
      alveolar percentage, proportional to both the first- and second-hour plasma
      concentrations, with a mean (SD) of 10.1% (8.4%) and 18% (16.7%), respectively.
      CONCLUSION: To our knowledge, the current study is the first that investigates
      whether standard doses of amikacin may lead to sufficient alveolar concentration
      of the drug. The results show that administration of amikacin in doses of 20
      mg/kg in critically ill patients with VAP may not provide sufficient
      concentrations in ELF.

PMID- 29471722
TI  - Outcomes and Resource Use Among Overweight and Obese Children With Sepsis in the
      Pediatric Intensive Care Unit.
AB  - OBJECTIVE: To evaluate the effect of overweight and obesity on outcomes and
      resource use among patients with sepsis in the pediatric intensive care unit
      (PICU). DESIGN: Retrospective analysis of clinical characteristics, resource use,
      and mortality among children 0 to 20 years of age admitted to the C.S.
      MottChildren's Hospital PICU (University of Michigan) between January 2009 and
      December 2015, with a diagnostic code for sepsis at admission (based on
      International Classification of Diseases, Ninth Revision- Clinical Modification
      codes) and with weight and height measurements at PICU admission. MEASUREMENTS
      AND MAIN RESULTS: A total of 454 participants met the inclusion criteria. Seventy
      six were categorized as underweight (body mass index [BMI] percentile <5th) and
      were excluded, which left a final sample size of 378 participants. Children with
      a BMI >5th and <85th percentiles for age were categorized as normal weight and
      those with a BMI >85th percentile as overweight/obese. After descriptive and
      bivariate analyses, multivariate regression methods were used to assess the
      independent effect of obesity status on mortality and the use of PICU technology
      after adjustment for patient age and illness severity at admission. Of the 378
      patients studied, 41.3% were overweight/obese. There was no difference in
      microbiologic etiology of sepsis ( P = .36), median PICU length of stay in days
      (5.4 vs 5.6; P = .61), or PICU mortality (6.4% vs 7.2%; P = .76) by weight
      status. The use of specialized PICU technology including extracorporeal membrane
      oxygenation (odds ratio [OR]: 2.77, 95% confidence interval [CI]:1.13-6.79) and
      continuous renal replacement therapy (OR: 4.58, 95% CI: 1.16-18.0) was higher
      among overweight/obese patients, compared with normal weight patients.
      CONCLUSIONS: Although PICU mortality and length of stay were similar for obese
      overweight patients and normal weight critically ill children with sepsis, there
      was significantly higher use of specialized organ-supportive technology among
      obese patients, likely indicating higher occurrence of multiple organ
      dysfunction.

PMID- 29471723
TI  - Minimally-invasive, microneedle-array extraction of interstitial fluid for
      comprehensive biomedical applications: transcriptomics, proteomics, metabolomics,
      exosome research, and biomarker identification.
AB  - Interstitial fluid (ISF) has recently garnered interest as a biological fluid
      that could be used as an alternate to blood for biomedical applications,
      diagnosis, and therapy. ISF extraction techniques are promising because they are
      less invasive and less painful than venipuncture. ISF is an alternative,
      incompletely characterized source of physiological data. Here, we describe a
      novel method of ISF extraction in rats, using microneedle arrays, which provides
      volumes of ISF that are sufficient for downstream analysis techniques such as
      proteomics, genomics, and extracellular vesicle purification and analysis. This
      method is potentially less invasive than previously reported techniques. The
      limited invasiveness and larger volumes of extracted ISF afforded by this
      microneedle-assisted ISF extraction method provide a technique that is less
      stressful and more humane to laboratory animals, while also allowing for a
      reduction in the numbers of animals needed to acquire sufficient volumes of ISF
      for biomedical analysis and application.

PMID- 29471724
TI  - Existential loneliness: An attempt at an analysis of the concept and the
      phenomenon.
AB  - BACKGROUND: According to ethical guidelines, healthcare professionals should be
      able to provide care that allows for the patients' values, customs and beliefs,
      and the existential issues that are communicated through them. One widely
      discussed issue is existential loneliness. However, much of the debate dealing
      with existential loneliness concludes that both the phenomenon and the concept
      are quite vague. AIM: To clarify what constitutes existential loneliness, and to
      describe its lived experiences. A further aim was to provide a definition of
      existential loneliness that can function as a tool for identifying the phenomenon
      and for differentiating it from other kinds of loneliness. METHOD: A literature
      review including theoretical and empirical studies. Different search strategies
      were used to gather the articles included in the study. The analysis of the
      empirical studies had an interpretative approach. The articles were also analysed
      with the aim of providing a definition of existential loneliness. This was done
      by means of criteria such as language, uniqueness, theory and usefulness. This
      study is not empirical and does therefore not require an ethics review. RESULTS:
      The analysis resulted in two main characteristics. The first one was perceiving
      oneself as inherently separated (disconnected) from others and from the universe.
      The second one brings out emotional aspects of EL, such as isolation, alienation,
      emptiness and a feeling of being abandoned. The empirical findings were divided
      into two categories: experiences of EL and circumstances in which EL arises. A
      definition of EL is also suggested, based on the two main characteristics
      identified. CONCLUSION: In order to meet patients' needs, it is an ethical duty
      for healthcare staff to be able to recognise experiences of EL, that is, to
      communicate with the patients about these experiences in an appropriate manner.
      This in turn demands knowledge about existential issues and skills to deal with
      them.

PMID- 29471725
TI  - Dignity from the nurses' and older patients' perspective: A qualitative
      literature review.
AB  - INTRODUCTION: Dignity is one of the most important values sensitively perceived
      by patients in nursing care. Older patients have been identified as having a high
      risk of losing their dignity in institutional care. To promote optimum nursing
      care, a deeper insight into the problem of older patients' dignity is needed.
      AIM: The aim was to identify, analyse and synthesise the qualitative evidence of
      dignity views and factors affecting it from the nurses' and older patients'
      perspective in the context of nursing care and to compare synthesised finding
      from the both perspective. METHODS: A literature review of qualitative evidence
      was chosen as a study design. The ENTREQ statement was implemented to enhance
      transparency. The CASP - Qualitative checklist and the thematic synthesis for
      synthesised findings were used. The electronic databases Academic Search
      Complete, CINAHL, Health Source: Nursing/Academic Edition, MEDLINE and PROQUEST
      were used to gather information for qualitative studies. RESULTS: A total of 306
      papers were retrieved. Fourteen qualitative studies met the inclusion criteria
      and were included in the review after methodological quality assessment using
      CASP. Four main themes of dignity from nurses' perspective were synthesised:
      seeing the patient as a unique person, communication and privacy, involving the
      patient, and working culture and environment. From the patients' perspective, six
      main themes were synthesised: autonomy and control, privacy, relationships, care
      and comfort, communication and identity. The comparison shows that the key
      difference is that older patients highlighted the theme relationships and nurses
      underlined the theme working culture and environment. CONCLUSION: The model
      structures of the older patients' dignity from both the nurses' and patients'
      perspectives support the idea of a multidimensional structure of human dignity.
      The resulting model might be used in a nursing self-reflection, in the management
      of the institutions providing all-day care for the older people and in the
      education and practice.

PMID- 29471726
TI  - Exploring dual disclosures for men who have sex with men in Mpumalanga, South
      Africa: a report from the field.
AB  - We explored to whom rural men who have sex with men (MSM) disclose their sexual
      identity and HIV status in Mpumalanga, South Africa. Participants were recruited
      using a modified snowball sampling method in order to complete a questionnaire.
      Descriptive and logistic regression analyses were conducted. There were 47
      participants of whom 22 self-reported as HIV-positive. Most participants
      disclosed their sexuality and HIV status to immediate family members and gay
      identified friends. We found that the longer someone had identified as MSM, the
      more likely they were to be HIV-positive and not go to clinic. Education and
      employment modified these findings. This study presents a broader picture of MSM
      in this rural African setting: that they do disclose their sexuality and HIV
      status to others in their community. However, more research is needed to develop
      these measures. We need to assess how long participants identify as MSM, how long
      they have been HIV-positive, and to whom they have disclosed these aspects of
      their lives to inform HIV prevention and treatment interventions for MSM in rural
      settings.

PMID- 29471727
TI  - Variations in Cigarette Smoking and Quit Attempts by Health Insurance Among US
      Adults in 41 States and 2 Jurisdictions, 2014.
AB  - OBJECTIVES: Information on the impact of health insurance on smoking and quit
      attempts at the state level is limited. We examined the state-specific prevalence
      of cigarette smoking and past-year quit attempts among adults aged 18-64 by
      health insurance and other individual- and state-level factors. METHODS: We used
      data from 41 states, the District of Columbia, and Puerto Rico, the jurisdictions
      that administered the Health Care Access module of the 2014 Behavioral Risk
      Factor Surveillance System. Data on quit attempts included current smokers with a
      past-year quit attempt and former smokers who quit during the past year. RESULTS:
      Overall, smoking prevalence ranged from 14.6% among those with private insurance
      to 34.7% among Medicaid enrollees, and past-year quit-attempt prevalence ranged
      from 66.4% among the uninsured to 71.5% among Medicaid enrollees. By insurance
      group, differences in the prevalence of state-specific past-year quit attempts
      ranged from 15 to 26 percentage points. Regardless of insurance type, people who
      were non-Hispanic white and had lower education levels were less likely to
      attempt quitting than were Hispanic people, non-Hispanic black people, and adults
      with more than a high school education. CONCLUSIONS: We found disparities in
      smoking and quit attempts by insurance status and state. Opportunities exist to
      increase access to cessation treatments through comprehensive state tobacco
      control programs and improved cessation insurance coverage, coupled with
      promotion of covered cessation treatments.

PMID- 29471729
TI  - Erratum.

PMID- 29471728
TI  - Derivation of Haploid Neural Stem Cell Lines by Selection for a Pax6-GFP
      Reporter.
AB  - Haploid cells facilitate genetic screening of recessive mutations for a single
      set of chromosomes. Haploid embryonic stem cells (haESCs) have been achieved in
      several species and widely utilized in genetic screens. The fact that haESCs
      undergo substantial diploidization during differentiation has limited the
      screening to other haploid cell types. In this study, we report a method to
      establish haploid neural stem cells (haNSCs) by selection for a Pax6 reporter. We
      inserted a green fluorescence protein (GFP) marker gene by homologous
      recombination into the Pax6 locus of an haESC line. GFP-positive haploid cells
      could be sorted and further cultured in the NSC medium for more than 30 passages.
      The established haNSCs expressed neural lineage markers and could differentiate
      into neurons, oligodendroglia, and astrocytes. Our study shows the feasibility of
      deriving haploid proliferative somatic cell lines using a genetically encoded
      reporter that suggest a system for genetic screening of neural and retinal
      development.

PMID- 29471730
TI  - Perceptions of why Malawians engage in concurrent sexual partnerships among a
      select population of radio listeners: findings from an exploratory study.
AB  - Concurrent sexual partnerships have been identified as a potential driver in the
      HIV epidemic in Southern Africa. This study utilised an innovative approach to
      explore perceptions of why Malawians may engage in these relationships, and their
      suggestions for reducing the practice among a select population of radio
      listeners. Using radio listener feedback in the form of text messages, we
      analysed approximately 1 000 text messages sent by individuals who listened to a
      reality radio programme that included real stories, told by Malawians, on topics
      related to HIV/AIDS. Listeners suggested that lack of satisfaction with one's
      partner was the overarching reason why individuals had concurrent sexual
      partnerships. Within the context of lack of satisfaction, listeners cited alcohol
      use, poor communication and gendered norms as factors related to satisfaction.
      Listeners suggested that couple communication could increase satisfaction, which,
      in turn, could reduce concurrent sexual partnerships. Prevention efforts should
      consider how to utilise couple communication to improve satisfaction as an
      approach to reduce HIV risk in Southern Africa.

PMID- 29471731
TI  - The role of pelvis-thorax coupling in controlling within-golf club swing speed.
AB  - Pelvis-thorax coordination has been recognised to be associated with swing speed.
      Increasing angular separation between the pelvis and thorax has been thought to
      initiate the stretch shortening cycle and lead to increased clubhead speed. The
      purpose of this study was to determine whether pelvis-thorax coupling played a
      significant role in regulating clubhead speed, in a group of low-handicap golfers
      (mean handicap = 4.1). Sixteen participants played shots to target distances
      determined based on their typical 5- and 6-iron shot distances. Half the
      difference between median 5- and 6-iron distance for each participant was used to
      create three swing effort conditions: "minus", "norm", and "plus". Ten shots were
      played under each swing effort condition using both the 5-iron and 6-iron,
      resulting in six shot categories and 60 shots per participant. No significant
      differences were found for X-factor for club or swing effort. X-factor stretch
      showed significant differences for club and swing effort. Continuous relative
      phase (CRP) results mainly showed evidence of the stretch shortening cycle in the
      downswing and that it was more pronounced late in the downswing as swing effort
      increased. Substantial inter-individual CRP variability demonstrated the need for
      individual analyses when investigating coordination in the golf swing.

PMID- 29471733
TI  - The influence of lotteries on employees' workplace HIV testing behaviour.
AB  - The aim of the study was to understand how lottery incentives influenced the HIV
      counselling and testing (HCT) behaviour and behaviour intention of shop-floor
      workers who participated in a workplace HCT campaign initiative in two companies
      in the Nelson Mandela Bay municipality, South Africa. A post-test only quasi
      experimental approach was used. The data were first collected, using a self
      administered cross-sectional survey instrument, among the control group (n = 88)
      followed by the experimental group (n = 110) after the advent of HIV testing and
      lotteries was announced. HIV testing behaviour data were collected on the days of
      the HIV testing events. The theory of planned behaviour (TPB) was used as guiding
      theory. Principal component analysis (PCA), t- and chi-square tests, and logistic
      regression were conducted to analyse the data. A significant increase in the mean
      scores of the experimental as compared to the control condition for the
      subjective norm's construct (t = -3.55, p < 0.001) and HIV testing behaviour
      intention (chi2 = 12.35, p < 0.001) was measured following the announcement of
      lottery incentives. The constructs of TPB explained 40% of the variance in HCT
      behaviour intention (R2 = 0.40). The strongest predictor of behaviour intention
      was the subjective norm (B = 0.435 and p < 0.001), followed by the attitudinal
      component (B = 0.323 and p = 0.040). The announcement of lotteries made shop
      floor workers develop a stronger intention to participate in workplace HIV
      testing through anticipation of stronger social support and encouragement. It was
      not possible to link behaviour intention to behaviour due to missing data. The
      findings point to the importance of providing workers with an opportunity to
      openly discuss HIV testing thus allowing mitigation of HIV stigma and
      discrimination and permitting HIV testing to become socially sanctioned and seen
      as part of a collective effort.

PMID- 29471732
TI  - Large Animal Models of an In Vivo Bioreactor for Engineering Vascularized Bone.
AB  - Reconstruction of large skeletal defects is challenging due to the requirement
      for large volumes of donor tissue and the often complex surgical procedures.
      Tissue engineering has the potential to serve as a new source of tissue for bone
      reconstruction, but current techniques are often limited in regards to the size
      and complexity of tissue that can be formed. Building tissue using an in vivo
      bioreactor approach may enable the production of appropriate amounts of
      specialized tissue, while reducing issues of donor site morbidity and infection.
      Large animals are required to screen and optimize new strategies for growing
      clinically appropriate volumes of tissues in vivo. In this article, we review
      both ovine and porcine models that serve as models of the technique proposed for
      clinical engineering of bone tissue in vivo. Recent findings are discussed with
      these systems, as well as description of next steps required for using these
      models, to develop clinically applicable tissue engineering applications.

PMID- 29471734
TI  - Probing light chain mutation effects on thrombin via molecular dynamics
      simulations and machine learning.
AB  - Thrombin is a key component for chemotherapeutic and antithrombotic therapy
      development. As the physiologic and pathologic roles of the light chain still
      remain vague, here, we continue previous efforts to understand the impacts of the
      disease-associated single deletion of LYS9 in the light chain. By combining
      supervised and unsupervised machine learning methodologies and more traditional
      structural analyses on data from 10 MUs molecular dynamics simulations, we show
      that the conformational ensemble of the DeltaK9 mutant is significantly
      perturbed. Our analyses consistently indicate that LYS9 deletion destabilizes
      both the catalytic cleft and regulatory functional regions and result in some
      conformational changes that occur in tens to hundreds of nanosecond scaled
      motions. We also reveal that the two forms of thrombin each prefer a distinct
      binding mode of a Na+ ion. We expand our understanding of previous experimental
      observations and shed light on the mechanisms of the LYS9 deletion associated
      bleeding disorder by providing consistent but more quantitative and detailed
      structural analyses than early studies in literature. With a novel application of
      supervised learning, i.e. the decision tree learning on the hydrogen bonding
      features in the wild-type and DeltaK9 mutant forms of thrombin, we predict that
      seven pairs of critical hydrogen bonding interactions are significant for
      establishing distinct behaviors of wild-type thrombin and its DeltaK9 mutant
      form. Our calculations indicate the LYS9 in the light chain has both localized
      and long-range allosteric effects on thrombin, supporting the opinion that light
      chain has an important role as an allosteric effector.

PMID- 29471737
TI  - Erratum.

PMID- 29471736
TI  - Incursions from the epicentre: Southern theory, social science, and the global
      HIV research domain.
AB  - Research about HIV constitutes a global domain of academic knowledge. The
      patterns that structure this domain reflect inequalities in the production and
      dissemination of knowledge, as well as broader inequalities in geopolitics.
      Conventional metrics for assessing the value and impact of academic research
      reveal that "Northern" research remains dominant, while "Southern" research
      remains peripheral. Southern theory provides a framework for greater critical
      engagement with knowledge produced by researchers within the global South. With a
      focus on HIV social science, we show that investigators working in and from
      Africa have produced and disseminated knowledge fundamental to the global domain
      of HIV research, and argue that their epistemological contribution may be
      understood within the framework of Southern theory. Through repurposing a
      bibliometrical measure of citation count, we constitute a new archive of highly
      cited social science research. With a focus on South Africa, we situate this
      archive within changing historical contexts, connecting research findings to
      developments in medicine, health sciences and politics. We focus on two key
      themes in the evolution of HIV knowledge: (1) the significance of context and
      locality - the "setting" of HIV research; and (2) sex, race and risk - changing
      ideas about the social determinants of HIV transmission.

PMID- 29471735
TI  - Cognitive impairment in older patients undergoing colorectal surgery.
AB  - Background With increasing numbers of older people being referred for elective
      colorectal surgery, cognitive impairment is likely to be present and affect many
      aspects of the surgical pathway. This study is aimed to determine the prevalence
      of cognitive impairment and assess it against surgical outcomes. Methods The
      Montreal Cognitive Assessment (MoCA) was carried out in patients aged more than
      65 years. We recorded demographic information. Data were collected on length of
      hospital stay, complications and 30-day mortality. Results There were 101
      patients assessed, median age was 74 years (interquartile range = 68-80), 54
      (53.5%) were women. In total, 58 people (57.4%) 'failed' the Montreal Cognitive
      Assessment test (score <= 25). There were two deaths (3.4%) within 30 days of
      surgery in the abnormal Montreal Cognitive Assessment group and none in the
      normal group. Twenty-nine (28.7%) people experienced a complication. The
      percentage of patients with complications was higher in the group with normal
      Montreal Cognitive Assessment (41.9%) than abnormal Montreal Cognitive Assessment
      (19.9%) ( p = 0.01) and the severity of those complications were greater (chi
      squared for trend p = 0.01). The length of stay was longer in people with an
      abnormal Montreal Cognitive Assessment (mean 8.1 days vs. 5.8 days, p = 0.03).
      Conclusion Cognitive impairment was common, which has implications for informed
      consent. Cognitive impairment was associated with less postoperative
      complications but a longer length of hospital stay.

PMID- 29471738
TI  - Exploring the binding interaction between herring sperm DNA and sunitinib:
      insights from spectroscopic and molecular docking approaches.

PMID- 29471739
TI  - Comparison and strategy of nitrogen removal at different low temperatures in a
      pilot-scale A2/O system.
AB  - To ensure low effluent total nitrogen (TN <= 15 mg L-1) and NH3-N( <= 5 mg L-1)
      at low temperatures (8.8-14.7 degrees C), a pilot-scale A2/O system with a low
      return activated sludge (200%) was employed to seek the optimal operation
      strategy. In the 90 days' experiment, the tests were separated into three stages
      (14.2 degrees C, 11.0 degrees C, and 9.1 degrees C), and the 49 samples were
      analysed. Our results showed that the nitrification was remarkably inhibited when
      the temperature was below 10 degrees C, while the denitrification was remarkably
      inhibited at the temperatures of 10-15 degrees C. Once the effluent NH3-N
      concentration was over 2.5 mg L-1, or [Formula: see text] concentration was over
      13 mg L-1, the effluent TN would be in excess of 15 mg L-1. When the temperature
      was over 10 degrees C, increasing dissolved oxygen (DO) was an optimal strategy
      to reduce the effluent NH3-N; nevertheless, when the temperature was below 10
      degrees C, simultaneously increasing DO and MLVSS would be carried out due to the
      low max. nitrification rates (36.0 mg (g-1 d-1)). If the carbon source
      (CODcr/[Formula: see text] ratio >= 7.3) was enough, increasing MLVSS was an
      effective method to relieve the negative influence of low temperature on
      denitrification.

PMID- 29471740
TI  - Orthophosphate modulates the phytotoxicity of nano-ZnO to Lemna minor (L.).
AB  - Because of their applications in large numbers of products, Zinc Oxide
      nanoparticles (nano-ZnO) will inevitably enter into the environment. Nano-ZnO
      released into the environment will be present in a complex matrix which can cause
      various chemical and physical transformations and modulate the biological
      reactivity of these particles. Due to their rapid growth and small size, Lemna
      minor is recommended by OECD for toxicological testing. Here, we tested how nano
      ZnO reactivity is modulated by the suite of macro- and micronutrients that are
      present in Lemna minor growth media. Specifically, we measured ex situ Reactive
      Oxygen Species (ROS) formation by nano-ZnO, and subsequent in planta toxicity.
      The data show how orthophosphate can modulate both ex situ ROS formation, and in
      planta toxicity. This has ramifications for phytotoxicity testing, which is
      commonly performed under controlled conditions and on media containing
      orthophosphate.

PMID- 29471741
TI  - Rabies in India: where do we stand?

PMID- 29471742
TI  - Does Missed Care in Isolated Rural Hospitals Matter?
AB  - Missed care is associated with adverse outcomes such as patient falls and
      decreased nurse job satisfaction. Although studied in populations of interest
      such as neonates, children, and heart failure patients, there are no studies
      about missed care in rural hospitals. Reducing care omissions in rural hospitals
      might help improve rural patient outcomes and ensure that rural hospitals can
      remain open in an era of hospital reimbursement dependent on care outcomes, such
      as through value-based purchasing. Understanding the extent of missed nursing
      care and its implications for rural populations might provide crucial information
      to alert rural hospital administrators and nurses about the incidence and
      influence of missed care on health outcomes. Focusing on missed care within rural
      hospitals and other rural health care settings is important to address the
      specific health needs of aging rural U.S. residents who are isolated from high
      volume, urban health care facilities.

PMID- 29471743
TI  - Masticatory performance parameters for young adults with "normal" occlusion.
AB  - Objective To develop reference data for young men/women on the variability of
      parameters used for the evaluation of masticatory function with an artificial
      test food. Methods Subjects included were 200 18-25-year olds with complete
      dentition and "normal" occlusion. An artificial test food was chewed in two tests
      (20 cycles and swallowing threshold), during which sequences/cycles were counted
      and timed. Medium-particle-size (MPS) and broadness of particle distribution were
      calculated evaluating the chewed material. Reference data was based on order
      statistics. Sex-specific 95% reference limits with 90% confidence intervals were
      calculated with RefVal-v2.1-software. Coefficients of variation were also
      obtained. Results Tables with reference data for young men/women chewing an
      artificial test food were constructed with the data collected displaying ample
      variability: MPS after 20 cycles anywhere between 0.7-3.5 mm or 14-84 cycles to
      deem the test food ready to be swallowed (C.V. 43% males/34% females). Conclusion
      There is much variability in masticatory parameters for young adults with good
      oral health.

PMID- 29471744
TI  - Injury-related gaining momentum as external causes of deaths in Ethiopian health
      and demographic surveillance sites: evidence from verbal autopsy study.
AB  - BACKGROUND: In Ethiopia, though all kinds of mortality due to external causes are
      an important component of overall mortality often not counted or documented on an
      individual basis. OBJECTIVE: The aim of this study was to describe the patterns
      of mortality from external causes using verbal autopsy (VA) method at the
      Ethiopian HDSS Network sites. METHODS: All deaths at Ethiopian HDSS sites were
      routinely registered and followed up with VA interviews. The VA forms comprised
      deaths up to 28 days, between four weeks and 14 years and 15 years and above. The
      cause of a death was ascertained based on an interview with next of families or
      other caregivers using a standardized questionnaire that draws information on
      signs, symptoms, medical history and circumstances preceding death after 45 days
      mourning period. Two physician assigned probable causes of death as underlying,
      immediate and contributing factors independently using information in VA forms
      based on the WHO ICD-10 and VA code system. Disagreed cases sent to third
      physician for independent review and diagnosis. The final cause of death
      considered when two of the three physicians assigned underlying cause of death;
      otherwise, labeled as undetermined. RESULTS: In the period from 2009 to 2013, a
      total of 9719 deaths were registered. Of the total deaths, 623 (6.4%) were from
      external causes. Of these, accidental drowning and submersion, 136 (21.8%),
      accidental fall, 113 (18.1%) and transport-related accidents, 112 (18.0%) were
      the topmost three leading external causes of deaths. About 436 (70.0%) of deaths
      were from the age group above 15 years old. Drowning and submersion and transport
      related accidents were high in age group between 5 and 14 years old. CONCLUSION:
      In this study, external causes of death are significant public health problems
      and require attention as one of prior health agenda.

PMID- 29471746
TI  - The trainee leadership blueprint: opportunities, benefits, and a call to action.
AB  - OBJECTIVE: Leadership experiences are vital not only to individual long-term
      career success but also the development, direction, and operation of higher
      spheres including professional organizations and the field of clinical
      neuropsychology itself. METHOD: The present paper presents a blueprint guide for
      neuropsychology trainees on available opportunities and resources for increasing
      their involvement in professional governance and developing leadership skills.
      First, we present a discussion of the benefits of leadership and professional
      service, including the acquisition of interpersonal skills and new professional
      competencies, the prospect of recognition and advancement, and the opportunity to
      participate in advocacy efforts. Then, we present an overview of existing
      opportunities for involvement, followed by the provision of specific, actionable
      items for trainees, mentors and leadership committees, and for neuropsychology
      organizations to ensure continued trainee engagement. CONCLUSIONS: These
      resources can serve as a guide for trainees and early career neuropsychologists
      seeking to acquire leadership proficiencies, and the recommendations aspire to
      promote advancement for trainees, professionals, and organizations alike.

PMID- 29471745
TI  - Effects of high ambient temperature on ambulance dispatches in different age
      groups in Fukuoka, Japan.
AB  - BACKGROUND: The elderly population has been the primary target of intervention to
      prevent heat-related illnesses. According to the literature, the highest risks
      have been observed among the elderly in the temperature-mortality relationship.
      However, findings regarding the temperature-morbidity relationship are
      inconsistent. OBJECTIVES: This study aimed to examine the association of
      temperature with ambulance dispatches due to acute illnesses, stratified by age
      group. Specifically, we explored the optimum temperature, at which the relative
      health risks were found to be the lowest, and quantified the health risk
      associated with higher temperatures among different age groups. METHODS: We used
      the data for ambulance dispatches in Fukuoka, Japan, during May and September
      from 2005 to 2012. The data were grouped according to age in 20-year increments.
      We explored the pattern of the association of ambulance dispatches with
      temperature using a smoothing spline curve to identify the optimum temperature
      for each age group. Then, we applied a distributed lag nonlinear model to
      estimate the risks of the 85th-95th percentile temperature relative to the
      overall optimum temperature, for each age group. RESULTS: The relative risk of
      ambulance dispatches at the 85th and 95th percentile temperature for all ages was
      1.08 [95% confidence interval (CI): 1.05, 1.12] and 1.12 (95% CI: 1.08, 1.16),
      respectively. In comparison, among age groups, the optimum temperature was
      observed as 25.0 degrees C, 23.2 degrees C, and 25.3 degrees C for those aged 0
      19, 60-79, and >=80, respectively. The optimum temperature could not be
      determined for those aged 20-39 and 40-59. The relative risks of high temperature
      tended to be higher for those aged 20-39 and 40-59 than those for other age
      groups. CONCLUSIONS: We did not find any definite difference in the effect of
      high temperature on ambulance dispatches for different age groups. However, more
      measures should be taken for younger and middle-aged people to avoid heat-related
      illnesses.

PMID- 29471747
TI  - Voices of leadership: wisdom from women leaders in neuropsychology.
AB  - OBJECTIVE: Inspired by panel discussions at various neuropsychology conferences,
      the aim of this paper is to share wisdom that women in neuropsychology acquired
      from their leadership experiences. METHOD: We identified 46 women leaders in
      governance and academic research through reviews of organizational websites and
      journal editorial boards, and requested their response to brief questions via
      email. Twenty-one leaders provided responses to three questions formulated by the
      authors. RESULTS: This paper summarizes the primary themes for the following
      questions: (1) What advice would you give to a woman neuropsychologist who is
      seeking to move into a leadership role? Responses included: increase visibility,
      make connections, know yourself, be confident, and gather information. (2) What
      leadership style(s) works best? No respondents endorsed a 'best' leadership
      style; however, they suggested that leaders should know their own personal style,
      be open and transparent, find a shared mission, and most importantly - use a
      collaborative approach. (3) What helps a woman earn respect as a leader in
      neuropsychology? Respondents recommended that leaders should: get involved in the
      work, demonstrate integrity, do your homework, be dependable, and keep meetings
      focused. CONCLUSIONS: It is the authors' intent that by gathering and distilling
      advice from successful women leaders in neuropsychology, more women may be
      catalyzed to pursue leadership roles in our profession.

PMID- 29471748
TI  - Editorial: raising awareness about gender bias and disparity in clinical
      neuropsychology and a call to action.

PMID- 29471749
TI  - Comparing mentorship and sponsorship in clinical neuropsychology.
AB  - OBJECTIVE: Mentoring is a well-known concept that is widely regarded as
      beneficial for personal and professional development. The concept of sponsoring
      is less recognized although it is considered critical by some for career
      advancement. The purpose of this study was to provide an initial exploration of
      differences between mentoring and sponsoring within neuropsychology and to learn
      what sponsors look for in proteges. METHOD: Twenty neuropsychologists with
      experience in mentorship and sponsorship were interviewed. Topics covered
      included the number of proteges they had mentored/sponsored, training received in
      mentoring/sponsoring, characteristics they look for in proteges, expectations of
      proteges, reasons they mentor/sponsor, and benefits of mentoring/sponsoring.
      RESULTS: On average, neuropsychologists interviewed had mentored 58 proteges and
      sponsored 40. None had ever received formal training in mentoring or sponsoring.
      Key characteristics needed for neuropsychologists to feel comfortable
      mentoring/sponsoring proteges were similar while those characteristics valued
      differed slightly with sponsored proteges valued for competence and getting
      things done and mentored proteges valued for interpersonal qualities. Reasons for
      and benefits of mentorship/sponsorship were similar, with rewarding feelings,
      satisfaction, and pride in the protege's successes at the top of the list.
      CONCLUSIONS: Neuropsychologists who provide training are in the position to
      mentor and sponsor individuals; mentoring relationships often entail sponsorship
      and vice versa such that the two constructs may be considered part of a
      continuum. Improving knowledge and skills in mentorship and sponsorship will not
      only advance personal and professional development of proteges but will also
      positively impact mentors/sponsors and help shape the field of neuropsychology in
      deliberate ways.

PMID- 29471750
TI  - Differential Transcriptome Analysis of Early Postnatal Developing Longissimus
      Dorsi Muscle from Two Pig Breeds Characterized in Divergent Myofiber Traits and
      Fatness.
AB  - Meat quality traits (MQTs) are very important in the porcine industry, which are
      mainly determined by skeletal muscle fiber composition, extra-muscular and/or
      intramuscular fat content. To identify the differentially expressed candidate
      genes affecting the meat quality traits, first we compared the MQTs and skeletal
      muscle fiber characteristics in the longissimus dorsi muscle (LDM) of the
      Northeast Min pig (NM) and the Changbaishan wild boar (CW) with their body weight
      approaching 90 kg. The significant divergences in the skeletal muscle fiber
      phenotypes and fatness traits between the two porcine breeds established an ideal
      model system for further identifying potential key functional genes that
      dominated MQTs. Further, a transcriptome profile analysis was performed using the
      Illumina sequencing method in early postnatal developing LDM from the two breeds
      at the ages of 42 days. Comparative analysis between these two cDNA libraries
      showed that there were 17,653 and 22,049 unambiguous tag-mapped sense transcripts
      detected from NM and CW, respectively. 4522 differentially expressed genes (DEGs)
      were revealed between the two tissue samples, of them, 4176 genes were found as
      having been upregulated and 346 genes were identified as having been
      downregulated in the NM library. By pathway enrichment analysis, a set of
      significantly enriched pathways were identified for the DEGs, which are
      potentially involved in myofiber development, differentiation and growth,
      lipogenesis and lipolysis in porcine skeletal muscle. The expression levels of 30
      out of the DEGs were validated by real-time quantitative reverse transcriptase
      PCR (qRT-PCR) and the observed result was consistent noticeably with the Illumina
      transcriptome profiles. The findings from this study can contribute to future
      investigations of skeletal muscle growth and development mechanism and to
      establishing molecular approaches to improve meat quality traits in pig breeding.

PMID- 29471751
TI  - Maternal serum thrombospondin-1 is significantly altered in cases with
      established preeclampsia.
AB  - PURPOSE: The aim of the study was to investigate whether maternal serum TSP-1
      level was associated with PE. MATERIALS AND METHODS: In our case control study,
      84 pregnant women in the third trimester were included. Forty-one of them were
      healthy and 43 of them were with the diagnosis of PE. The diagnosis was based on
      the definitions of the National High Blood Pressure Education Program working
      Group on High Blood Pressure in Pregnancy. Preeclamptic patients were divided
      into two subgroups as mild and severe. Blood pressure (BP) of pregnant women were
      obtained in left-side lying position using a mercury sphygmomanometer after at
      least 10 minutes of rest. Ten milliliters of venous blood was taken from every
      pregnant women and dispensed into lithium heparin and serum was obtained. Samples
      were stored at -80  degrees C until analyzed. Serum TSP-1 level was measured
      using enzyme-linked immunosorbent assay (ELISA). All tests were two-tailed and p
      < .05 was considered to be statistically significant. RESULTS: TSP-1 level was
      significantly lower in PE group than in controls (p = .003). Platelet counts were
      similar in two groups (p = .26). TSP-1 levels were significantly lower in severe
      PE than in mild PE cases. According to the subgroup analysis, TSP-1 level was
      found significantly lower in severe preeclampsia group compared to control group
      (p = .015). CONCLUSIONS: In light of the association between endothelial
      dysfunction and preeclampsia, we claim that lower levels of TSP-1 which is
      released mostly from endothelial cells seem to reflect disease severity in PE.
      Our study reveals that maternal serum TSP-1 levels decrease in pregnant women
      presenting with PE and TSP-1 may be a new biomarker for the detection of PE and
      even severity of it. Further studies especially prospective ones with greater
      numbers of cases are needed.

PMID- 29471752
TI  - Simultaneous removal of nitrate and hydrogen sulfide by autotrophic
      denitrification in nitrate-contaminated water treatment.
AB  - Nitrate contamination is a risk to human health and may cause eutrophication,
      whereas H2S is an undesirable constituent in biogas. In order to better
      understand denitrification using gaseous H2S as electron donor, this study
      investigated denitrification at different molar ratios of sulfur and nitrogen
      (S/N ratios) and H2S dosages. Although nitrate continued to decrease, a lag in
      sulfate generation was observed, implying the generation of sulfide oxidizing
      intermediates, which accumulated even though nitrate was in excess at lower S/N
      ratios of 0.19 and 0.38. More addition of H2S could result in a longer lag of
      sulfate generation. Before depletion of dissolved sulfide, denitrification could
      proceed with little nitrite accumulation. High throughout sequencing analysis
      identified two major genera, Thiobacillus and Sulfurimonas, that were responsible
      for autotrophic denitrification. The simultaneous removal of nitrate and H2S
      using a wide range of concentrations could be achieved.

PMID- 29471753
TI  - Evaluation of virus reduction at a large-scale wastewater reclamation plant by
      detection of indigenous F-specific RNA bacteriophage genotypes.
AB  - Evaluating the reduction of virus load in water reclamation plants is important
      to ensuring the hygienic safety of the reclaimed water. A virus-spiking test is
      usually used to estimate virus reduction but is not practicable at large-scale
      plants. Thus, we evaluated virus reduction by ultrafiltration (UF) plus
      ultraviolet (UV) irradiation at a large-scale reclamation plant (1000 m3/d) by
      quantifying indigenous F-specific RNA bacteriophages (FRNAPHs). To detect the
      infectious FRNAPH, we used both plaque assay and integrated culture-reverse
      transcription polymerase chain reaction combined with the most probable number
      assay, which can detect infectious FRNAPH genotypes. For comparison, we
      determined reductions of indigenous FRNAPHs and spiked MS2 at a small-scale pilot
      plant (10 m3/d) at the same time. Reductions by UF were not significantly
      different among the bacteriophages at pilot plants. This result suggests that
      indigenous bacteriophages could be used for evaluating virus reduction by UF at
      large-scale plants. Indigenous Genotype I (GI) FRNAPH showed the highest UV
      resistance, followed by GII, GIII, and GIV. The resistance of GI-FRNAPH was
      equivalent to that of spiked MS2. The reduction of the total infectious FRNAPHs
      determined by plaque assay was affected by the predominant FRNAPH genotype,
      presumably because of their different UV resistances. Our results reveal that
      indigenous GI-FRNAPH can be a good alternative indicator to spiked MS2 in view of
      virus reduction during water reclamation. The reclaimed water from our large
      scale reclamation plant could be used for irrigation because the expected
      reduction (6.3 log10) of indigenous GI-FRNAPH achieved the Title 22 (>5 log10).

PMID- 29471754
TI  - Anoctamin Channels in Human Myometrium: A Novel Target for Tocolysis.
AB  - BACKGROUND: Spontaneous preterm labor leading to preterm birth is a significant
      obstetric problem leading to neonatal morbidity and mortality. Current tocolytics
      are not completely effective and novel targets may afford a therapeutic benefit.
      OBJECTIVE: To determine whether the anoctamin (ANO) family, including the calcium
      activated chloride channel ANO1, is present in pregnant human uterine smooth
      muscle (USM) and whether pharmacological and genetic modulation of ANO1 modulates
      USM contraction. METHODS: Reverse transcription-polymerase chain reaction (RT
      PCR), quantitative RT-PCR, and immunohistochemical staining were done to
      determine which members of the ANO family are expressed in human USM. Uterine
      smooth muscle strips were studied in an organ bath to determine whether ANO1
      antagonists inhibit oxytocin-induced USM contractions. Anoctamin 1 small
      interfering RNA (siRNA) knockdown was performed to determine its effect on
      filamentous-/globular (F/G)-actin ratio, a measurement of actin polymerization's
      role in promoting smooth muscle contraction. RESULTS: Messenger RNA (mRNA)
      encoding all members of the ANO family (except ANO7) are expressed in pregnant
      USM tissue. Anoctamin 1 mRNA expression was decreased 15.2-fold in pregnant USM
      compared to nonpregnant. Anoctamin 1 protein is expressed in pregnant human USM
      tissue. Functional organ bath studies with pregnant human USM tissue demonstrated
      that the ANO1 antagonist benzbromarone attenuates the force and frequency of
      oxytocin-induced contractions. In human USM cells, siRNA knockdown of ANO1
      decreases F-/G-actin ratios. CONCLUSION: Multiple members of the ANO family,
      including the calcium-activated chloride channel ANO1, are expressed in human
      USM. Antagonism of ANO1 by pharmacological inhibition and genetic knockdown leads
      to an attenuation of contraction in pregnant human USM. Anoctamin 1 is a
      potentially novel target for tocolysis.

PMID- 29471755
TI  - Sustained return to work and work participation after a new legislation
      obligating employers to notify prolonged sickness absence.
AB  - AIMS: Return to work (RTW) after prolonged sickness absence benefits both the
      individual and society. However, the effectiveness of legislation aiming to
      improve RTW remains uncertain. We examined whether sustained RTW and work
      participation were different before and after a legislative change enacted in
      2012 (i.e. an intervention) that obligated employers to give notice of prolonged
      sickness absence to occupational health services. METHODS: Two random samples
      (2010 and 2013) of the Finnish working aged population (70%, ~2.6 million each)
      were drawn. Using survival analysis, we assessed sustained RTW (>=28 consecutive
      working days) during a two-month follow-up after a sickness absence minimum of 30
      calendar days in the pre- and post-intervention period. We also identified
      pathways for RTW with cluster analysis and calculated relative gain in work
      participation in the total sample and by several population subgroups. RESULTS:
      In the total sample, sustained RTW was 4% higher and the mean time to sustained
      RTW was 0.42 days shorter in the post- than in the pre-intervention period. The
      estimates were larger among women than men and among those with mental disorders
      compared with other diagnoses. Changes in the pathways for sustained RTW
      indicated a 4.9% relative gain in work participation in the total sample. The
      gain was larger among those who lived in areas of low unemployment rate (20.6%)
      or worked in the public sector (11.9%). CONCLUSIONS: From 2010 to 2013, RTW and
      work participation increased among the employees with prolonged sickness absence,
      suggesting that the legislative change enhanced RTW. The change in work
      participation varied by population subgroup.

PMID- 29471756
TI  - Age and gender differences in the impact of labour-market transitions on
      subjective health in Germany.
AB  - AIMS: Applying a gender- and age group-sensitive approach, we investigated the
      effect of labour-market transitions (job loss and re-employment) on subjective
      physical and mental health. METHODS: A combination of the difference-in
      differences approach and propensity score matching controls for selectivity and
      initial health differences. This allowed us to analyse the causal effect of job
      loss and re-employment on subjective health. We made use of data from the German
      Panel Study Labour Market and Social Security and combined survey information
      with administrative records of the Federal Employment Agency for employed and
      unemployed men and women 31-60 years of age ( n = 2213). We controlled for labour
      market experiences before the time period under study and for labour-market
      transitions between the interviews. Subjective health was assessed using the SF
      12 health questionnaire, enabling us to differentiate between subjective mental
      and physical health functioning. RESULTS: We found that physical health was
      affected mainly in older persons between 45 and 60 years old. Controlling for
      covariates using propensity score matching, mental health was affected only when
      living-wage jobs (i.e. jobs that provide sufficient income to achieve a defined
      minimum standard of living above the social benefit level) are gained or lost.
      Younger women showed a significant improvement in mental health after re
      employment. In contrast, job loss affected only older individuals' mental health,
      with a particularly negative effect observed for men. CONCLUSIONS: Our results
      not only showed that women and men are affected differently by job loss and re
      employment, but also that age is an important factor. Older men were affected
      most severely by job loss, whereas re-employment was found to improve mental
      health only in women aged 31-44 years. It is therefore important to address the
      health problems of different socio-demographic groups separately, and to apply
      active labour-market policies with regard to unemployed men and women with health
      impairments. Based on our results, we suggest the promotion of employment with
      income levels above the maximum welfare benefit award.

PMID- 29471757
TI  - Unfit for work: Health and labour-market prospects.
AB  - AIM: The aim of this study was to examine whether health status (number of
      chronic diseases, health shock and use of tranquilizers/sleeping pills) is
      related to labour-market outcomes later in life. METHODS: Twin data for Finnish
      men and women who were at least 33 years old in 1990 were linked to comprehensive
      register-based information on unemployment and the incidence of disability
      pension. We used the within-twin dimension of the data to account for shared
      family and genetic factors. Self-reported information on the number of diagnosed
      chronic diseases, health shock and drug use were obtained from the 1975 and 1981
      twin surveys, when the twins were at least 18 years old. Unemployment months and
      the incidence of disability pension were measured during prime working age over
      the 1990-2004/2009 period. RESULTS: Poor health status is significantly
      positively related to unemployment and the incidence of disability pension. The
      results are robust to controlling for shared family and genetic factors and the
      key measures of risky health behaviours (alcohol use, lifetime smoking and body
      mass index). CONCLUSIONS: Health status is a fundamental determinant of long-term
      labour-market outcomes.

PMID- 29471758
TI  - Impact of a personalised active labour market programme for persons with
      disabilities.
AB  - AIMS: The paper estimates the impact of a supported employment programme
      implemented in Hungary. METHODS: This is a non-experimental evaluation using a
      matching identification strategy supported by rich data on individual
      characteristics, personal employment and unemployment history and the local
      labour market situation. We use a time-window approach to ensure that programme
      participants and matched controls entered unemployment at the same point in time,
      and thus faced very similar labour market conditions. RESULTS: We find that the
      programme had a positive effect of 16 percentage points on the probability of
      finding a job among men and 25 percentage points among women. The alternative
      outcome indicator of not re-entering the unemployment registry shows somewhat
      smaller effects in the case of women. CONCLUSIONS: In comparison to similarly
      costly programmes that do not facilitate employment in the primary labour market,
      rehabilitation services represent a viable alternative.

PMID- 29471759
TI  - Pieces in a big puzzle: On the relationship between health and employment.

PMID- 29471760
TI  - Working while on a disability pension in Finland: Association of diagnosis and
      financial factors to employment.
AB  - AIMS: The aim of this study was to find out whether health and financial factors
      are associated with engagement in paid work during a disability pension. METHODS:
      The data included a 10 per cent sample of Finns aged 20-62 years who were drawing
      earnings-related full or partial disability pension in 2012 ( n = 14,418).
      Logistic regression analysis was used to estimate odds ratios for working while
      on a full or partial disability pension. RESULTS: Fourteen per cent of full
      disability pensioners and 76 per cent of partial disability pensioners were
      engaged in paid work. Full disability pensioners due to mental disorders were
      working less often than full disability pensioners due to other diseases. Partial
      disability pensioners due to cardiovascular diseases were working more than
      partial disability pensioners due to other diseases. More recent timing of
      disability pension was associated with working for both partial and full
      disability pensioners. Working while on disability pension was more common among
      those with higher education. Partial disability pensioners with average pension
      worked more often than those with high pension. CONCLUSIONS: By knowing the
      factors associated with working while on a disability pension, policies could be
      more efficiently allocated to encourage disability pensioners to take up work.
      One way would be to support disability pensioners with low education to work
      more. Another way to increase work among disability pensioners is to support the
      recently retired in working longer.

PMID- 29471761
TI  - Health and retirement age: Comparison of expectations and actual retirement.
AB  - AIM: We examine the relationship between the subjective assessment of health
      status and retirement by using information on expected and actual retirement
      ages. METHODS: Subjective data from cross-sectional surveys, conducted in Finland
      in 2003 and 2008, are linked to information on actual retirement age from
      register data from 2003 to 2013. Regression models are estimated for actual and
      expected retirement ages. RESULTS: While the health status is positively
      correlated with both actual and anticipated full-time retirement age, the actual
      age of retirement is less sensitive to health. On average, individuals tend to
      retire later than they had anticipated. We examine potential biases in the health
      retirement relationship. Measurement error in regard to health status biases the
      results downwards. Using data on observed retirement ages, omitting those who do
      not retire during the data period, leads to a selection problem. Ignoring the
      selection also leads to a downwards bias in the health-retirement age connection.
      As a more exogenous health variable we use health shocks, which are measured by
      average annual days of absence due to sickness in the follow-up period. These
      shocks are negatively related to retirement age in a subsample of initially
      healthy individuals. CONCLUSIONS: When subjective assessment of health is used
      for explaining retirement behavior, the effects of health can often be
      underestimated rather than overestimated. To lengthen working careers, attention
      should be given to both the ability (health) and willingness (perceptions of
      proper retirement age) of people to continue longer at work.

PMID- 29471762
TI  - Impact of cocaine use on protease inhibitor-associated dyslipidemia in HIV
      infected adults.
AB  - Previous studies have demonstrated a link between protease inhibitor (PI)-based
      therapy and lipid dysregulation. The main objective of this study was to examine
      whether cocaine use may modify PI-associated dyslipidemia in adults. Between June
      2003 and June 2014, 957 human immunodeficiency virus (HIV)-infected participants
      in Baltimore, Maryland were enrolled in a study that investigated
      HIV/antiretroviral therapy-associated comorbidities. Multiple linear and logistic
      regression models were fitted to examine the associations between PI therapy and
      lipid profiles for the pooled sample and cocaine use subgroups, respectively.
      Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC/high
      density lipoprotein cholesterol (HDL-C) ratio, and atherogenic index of plasma
      (AIP) levels were positively associated with duration of PI-based therapy in long
      term cocaine users (all p < 0.05). However, longer-term PI therapy was
      significantly associated with increased HDL-C in non-chronic cocaine users (beta
      = 0.109, SE = 0.042, p < 0.05). The participants who received PI therapy >=12
      months and used cocaine >=15 years were more likely to have hypertriglyceridemia
      (OR = 2.82, 95% CI = 1.63, 4.88) and abnormal AIP (OR = 1.73, 95% CI = 1.08,
      2.79) as compared to their counterparts. Our findings showed that long-term
      cocaine use may exacerbate adverse effects of PI therapy on lipid metabolism,
      suggesting that reduced cocaine use may be considered an alternative approach to
      managing PI-associated dyslipidemia in chronic cocaine users with HIV infection.

PMID- 29471763
TI  - Risk factors associated with sexually transmitted infections among women under
      community supervision in New York City.
AB  - The number of women under community supervision in the United States has
      increased, and this population has a high risk for sexually transmitted
      infections (STIs). We examined STI prevalence and multiple risk factors among
      drug-involved women under community supervision in New York City. Data were from
      a randomized controlled trial testing the efficacy of a behavioral HIV/STI
      intervention (Women on the Road to Health [WORTH]) among drug-involved women in
      the community corrections system in New York City from 2009 to 2012. To be
      eligible for inclusion, women had to be under community supervision within the
      past 90 days, have used illicit drugs at least once in the past six months, and
      have unprotected sex at least once in the past 90 days. Participants completed a
      survey containing items on STI risk factors and were tested for Chlamydia
      trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Multivariable
      regression was used to examine associations between risk factors and STI
      diagnosis. Of 333 women tested, 89 (26.7%) tested positive for an STI. Ten (3.0%)
      were positive for C. trachomatis, 4 (1.2%) for N. gonorrhoeae, and 77 (23.1%) for
      T. vaginalis. Women with any STI were more likely to be black (AOR: 2.02; 95% CI:
      1.08-3.77), homeless in the past 90 days (AOR: 2.07; 95% CI: 1.01-4.26), arrested
      in the past 90 days (AOR: 1.97; 95% CI: 1.14-3.39), and have a greater number of
      sexual partners in the past 90 days (AOR: 1.24; 95% CI: 1.08-1.42). Drug-using
      women under community supervision have a high burden of STIs driven by multiple
      risk factors. Implementing STI screening, prevention, and treatment programs in
      community supervision settings could facilitate a reduction in STIs among this
      population.

PMID- 29471764
TI  - Oropharyngeal HPV infection: prevalence and sampling methods among HIV-infected
      men in South Africa.
AB  - Worldwide, 96,000 cases of oropharyngeal cancer (OPC) occurred in 2012. Human
      papillomavirus (HPV) is a risk factor for OPC. Data on oropharyngeal HPV
      infection are limited. There is no consensus on the best sampling method for
      detecting the infection. We describe the prevalence of oropharyngeal HPV
      infection among HIV-infected men and compare the performance of oral rinses and
      swabs in detecting oropharyngeal HPV infection. Paired oral rinses and swabs for
      181 men were tested for HPV DNA using the Roche Linear Array. Performance was
      determined by the number of infections detected and the percentage of samples
      with adequate DNA extraction. Agreement between sampling methods was assessed by
      the kappa statistic. Prevalence of oropharyngeal HPV infection with rinse samples
      was 1.8% (three infections) and 0.6% (one infection) with swabs (p = 0.06).
      Adequate cellular DNA extraction was more likely with rinse (93.4%) than swab
      samples (89.0%, p = 0.05). There was moderate agreement between the methods
      (kappa = 0.49). The prevalence of oropharyngeal HPV DNA infection among this
      predominantly heterosexual sample of men living with HIV was low and consistent
      with the infrequent oral sex practices. Oral rinse performed better than oral
      swab in detecting oropharyngeal HPV DNA infection and might contribute to
      screening for OPCs.

PMID- 29471765
TI  - Non-consensual sterilization of women living with HIV.
AB  - Women living with HIV are stigmatized and discriminated against. They often wish
      to have children, but they are subjected to the practice of forced (involuntary)
      sterilization in at least 27 countries under the guise of protecting maternal
      health and preventing the birth of infected infants. Some women are not asked to
      give consent, or a third party consents on their behalf. Others are given
      insufficient information or fed misinformation. The circumstances under which
      such women have been asked to sign consent forms for sterilization include fear,
      coercion, intimidation, and undue influence. Courts have been clear that such
      practice is a breach of human rights, but, so far, it has not been formally
      declared in courts that such practice constitutes discrimination. More needs to
      be done in terms of education, sanctions against those who carry out this
      practice, and help for victims.

PMID- 29471768
TI  - Their Time Has Come: Providing Culturally Competent Care to LGBT Older Adults.

PMID- 29471769
TI  - Providing Competent and Affirming Services for Transgender and Gender
      Nonconforming Older Adults.
AB  - Despite the growing visibility and acceptance of transgender and gender
      nonconforming (TGNC) individuals, TGNC older adults experience many barriers in
      accessing competent and affirming health and social services due to anti-TGNC
      prejudice, discrimination, and lack of competent healthcare training on the part
      of healthcare workers. Clinical gerontologists and geriatricians will likely
      encounter TGNC adults in their practice given population aging and greater
      numbers of TGNC people who are living in their affirmed gender identities. The
      American Psychological Association recently published its Guidelines for
      Psychological Practice with Transgender and Gender Nonconforming People, which
      document the unique needs of TGNC individuals and outlines approaches for
      competent and affirming service provision (APA, 2015). We interpret these
      Guidelines using a gerontological lens to elucidate specific issues faced by the
      TGNC older adult along with the practice and policy implications for this
      population.

PMID- 29471770
TI  - Exploring Staff Clinical Knowledge and Practice with LGBT Residents in Long-Term
      Care: A Grounded Theory of Cultural Competency and Training Needs.
AB  - OBJECTIVES: Existing literature shows that LGBT residents are likely to face
      suboptimal care in LTC facilities due to prejudice and discriminatory policies.
      The aim of this project was to assess the LGBT cultural competency of staff
      working in LTC facilities, identify their current training needs, and develop a
      framework for understanding LGBT cultural competency among LTC staff and
      providers. METHODS: This grounded theory study comprised data from focus groups
      of interdisciplinary staff from three LTC facilities. RESULTS: Results suggested
      that LTC staff struggle with how to be sensitive to LGBT residents' needs.
      Tension appeared to exist between wanting to provide an equal standard of care to
      all LTC residents and fearing they would show "favoritism" or "special
      treatment," which might be viewed as unprofessional. Participants indicated
      training could help to address the ambivalence they experience about providing
      sensitive care to subpopulations of residents who face stigma and oppression.
      CONCLUSIONS: LTC staff stand to benefit from cultural competency training focused
      on LGBT residents. Training should be not only informational in nature, but also
      facilitate greater self-awareness and self-efficacy with respect to providing
      care to LGBT people.

PMID- 29471771
TI  - The Effect of a Self-management Program on the Quality-of-Life of Community
      dwelling Older Adults with Chronic Musculoskeletal Knee Pain: A Pilot Randomized
      Controlled Trial.
AB  - OBJECTIVES: To evaluate a 6-week self-management program on pain conducted in a
      mobile setting at the residences of older adult participants. METHODS: In this
      single-blinded randomized controlled trial, 46 community-dwelling older adults
      with chronic knee pain were randomly assigned to the experimental (n = 19) and
      wait-list control groups (n = 27). The experimental group engaged in the 6-week
      program while the control group was only given some pamphlets on exercise and
      joint care. The pain level, physical functions, QOL, and self-efficacy of the
      participants in both groups were assessed at baseline, post-program, and at the 1
      month follow-up session. Both baseline and post-program (or post-control-period
      assessment) data were analyzed. RESULTS: The results showed that the participants
      in the experimental group had a higher level of self-efficacy, better performance
      in walking test, a higher level of quality-of-life, and less frequency of pain at
      the post-program follow-up as compared to the control group. The effect was
      maintained among the experimental group at post-4-week follow-up and further
      reduction in pain was detected. CONCLUSIONS: The program appeared to be effective
      at improving the pain status, self-efficacy, functional performance, and quality
      of-life of older adults. However, as the sample size was small, further study is
      suggested to investigate the effects of the program.

PMID- 29471772
TI  - A Randomized Control Study on Psycho-Education Group on Improving Health-Related
      Quality of Life of Chinese Persons with Major Neurocognitive Disorder.
AB  - OBJECTIVES: People with a major neurocognitive disorder (PwND) are found to have
      a lower health related quality of life (HRQoL) than those without neurocognitive
      disorder. This research study aims to evaluate the effectiveness of a psycho
      education group in improving the HRQoL of Chinese PwND. METHODS: By adopting
      randomized control trial (RCT), Chinese PwND were randomly assigned to either a
      10-session psycho-education group or the control group. Family caregivers of
      treatment group were encouraged to take part in two sessions focusing on the
      caring and communication skills. Control group and their family caregivers
      received standardized educational materials on basic information on
      neurocognitive disorder for them to read at home. Standardized assessment was
      conducted both with PwND and their caregivers independently to give the self
      rated and caregiver-rated HRQoL of PwND in the pre- and post- treatment periods
      by a research assistant who was blind to the group assignment of the
      participants. Moreover, qualitative interviews were also conducted for ten
      participants and five family caregivers of the treatment group to identify those
      group elements relating to its effectiveness. RESULTS: 2 * 2 repeated measures
      ANCOVA demonstrated that the treatment group (n = 32) was significantly more
      effective than the control group (n = 32) in improving the caregiver-rated HRQoL
      (F[1, 61] = 4.35, p = .04 < .05) with a moderate effect size, but not self-rated
      HRQoL, Qualitative analysis suggested several group elements relating to its
      effectiveness. CONCLUSIONS: This present RCT shows that the psycho-education
      group significantly improves caregiver-rated HRQoL of PwND, supporting the
      feasibility and effectiveness of the psycho-education group.

PMID- 29471773
TI  - Religiousness and Psychological Distress in Jewish and Christian Older Adults.
AB  - OBJECTIVES: In this study, the authors explore how the association between
      religiousness and psychological distress varies by religious affiliation. Prior
      work has shown that the association between religious belief and psychological
      distress is stronger for Christians than Jews, while religious activity is
      associated with lower psychological distress for both groups. METHODS: Interviews
      were conducted using a community sample of 143 Christian and Jewish older adults,
      ages 65 and over. Quantitative measures were used to assess levels of
      organizational and intrinsic religiosity, as well as symptoms of depression and
      anxiety. RESULTS: Christians who are highly involved in the organizational
      aspects of their religion report fewer depressive symptoms than Jews who have
      high levels of organizational religiosity, and the opposite is the case at lower
      levels of organizational religiosity. No significant group differences were found
      in the relationship between religiousness and anxiety. CONCLUSIONS: The results
      of this study indicate a difference between Jews and Christians in the reasons
      that they turn to their respective religious services, particularly in late life.

PMID- 29471774
TI  - Cognitive Training Program to Improve Working Memory in Older Adults with MCI.
AB  - OBJECTIVES: Deficits in working memory (WM) are associated with age-related
      decline. We report findings from a clinical trial that examined the effectiveness
      of Cogmed, a computerized program that trains WM. We compare this program to a
      Sham condition in older adults with Mild Cognitive Impairment (MCI). METHODS:
      Older adults (N = 68) living in the community were assessed. Participants
      reported memory impairment and met criteria for MCI, either by poor delayed
      memory or poor performance in other cognitive areas. The Repeatable Battery for
      the Assessment of Neuropsychological Status (RBANS, Delayed Memory Index) and the
      Clinical Dementia Rating scale (CDR) were utilized. All presented with normal
      Mini Mental State Exams (MMSE) and activities of daily living (ADLs).
      Participants were randomized to Cogmed or a Sham computer program. Twenty-five
      sessions were completed over five to seven weeks. Pre, post, and follow-up
      measures included a battery of cognitive measures (three WM tests), a subjective
      memory scale, and a functional measure. RESULTS: Both intervention groups
      improved over time. Cogmed significantly outperformed Sham on Span Board and
      exceeded in subjective memory reports at follow-up as assessed by the Cognitive
      Failures Questionnaire (CFQ). The Cogmed group demonstrated better performance on
      the Functional Activities Questionnaire (FAQ), a measure of adjustment and far
      transfer, at follow-up. Both groups, especially Cogmed, enjoyed the intervention.
      CONCLUSIONS: Results suggest that WM was enhanced in both groups of older adults
      with MCI. Cogmed was better on one core WM measure and had higher ratings of
      satisfaction. The Sham condition declined on adjustment.

PMID- 29471775
TI  - Coping: Impact of Gender and Stressful Life Events in Middle and in Old Age.
AB  - OBJECTIVES: This study seeks to identify different life events that participants
      considered stressful and to study the joint effect of gender, age group, and main
      stressful life events on the use of different coping strategies. METHODS: The
      sample comprised 243 men and women, 55 to 99 years old, who attended senior
      activity centers. Analyses were conducted using multivariate analysis of variance
      (MANOVA). RESULTS: Three main categories of stressful life events were
      identified: health problems, family problems, and other problems. Significant
      main effects of gender and stressful life events, and marginal effects of age
      group on coping strategies were found. Furthermore, an interaction between gender
      and age group, and also between gender and stressful life events emerged in some
      of the coping strategies analyzed. CONCLUSIONS: Age, gender or type of stressful
      situation impact on the coping strategies used by older people. Older men and
      women were found to use different strategies depending upon the situation they
      are facing and upon their age group. The results may prove useful to
      practitioners and clinicians who directly work with older people and may help
      clinicians provide effective coping strategies to address the specific life
      events that older adults find stressful.

PMID- 29471777
TI  - Spontaneous and Drug-induced Arteritis/Polyarteritis in the Gottingen Minipig
      Review.
AB  - Arteritis/polyarteritis occurs spontaneously in many species used in preclinical
      toxicology studies. In Gottingen minipigs, arteritis/polyarteritis is an
      occasionally observed background change. In the minipig, this finding differs in
      frequency and nature from age-related polyarteritis nodosa in rats or monkeys,
      and Beagle pain syndrome in dogs. In minipigs, it can be present in a single
      small- or medium-sized artery of an organ or a few organs and is most commonly
      recorded in the cardiac and extracardiac blood vessels, vagina, oviduct, rectum,
      epididymis, spinal cord, pancreas, urinary bladder, kidneys, and stomach. The
      etiology is unknown although it has been considered in minipigs as well as in
      rats, dogs, and monkeys to be possibly immune mediated. This background change is
      important with respect to its nature and distribution in the minipig in order to
      distinguish it from drug-induced vascular changes, which might occur in similar
      locations and have similar morphologic features. This review summarizes the
      morphology, incidence, and predilection sites of arteritis as a spontaneously
      occurring background change and as a drug-induced vasculopathy in the minipig,
      and also describes the main aspects to consider when evaluating vascular changes
      in Gottingen minipig toxicity studies and their human relevance.

PMID- 29471776
TI  - T-cell Immunotherapies and the Role of Nonclinical Assessment: The Balance
      between Efficacy and Pathology.
AB  - Gene-engineered T-cell therapies have the potential to revolutionize the
      treatment of cancer. These therapies have shown exceptional clinical efficacy
      specifically in the field of B-cell malignancies and the first products
      (KymriahTM and YescartaTM) have recently been approved in the United States for
      specific indications. The power of these treatments is also linked with a
      distinct set of toxicities both predicted and unpredicted, including off-tumor
      activity, cytokine release syndromes, and neurotoxicity, occasionally with fatal
      consequences. As these therapies begin to reach more patients, it is critical to
      develop the nonclinical tools to adequately determine the mechanisms driving
      these toxicities, to assess the safety risks of candidate products, and to
      develop strategies for safety management.

PMID- 29471778
TI  - Evaluation of Uracil, Sodium Ascorbate, and Rosiglitazone as Promoters of Urinary
      Bladder Transitional Cell Carcinomas in Male Sprague-Dawley Rats.
AB  - The purpose of this study was to establish a 2-stage model of urinary bladder
      carcinogenesis in male Sprague-Dawley rats to identify tumor promoters. In phase
      1 of the study, rats ( n = 170) were administered 100 mg/kg of the tumor
      initiator, N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), twice weekly by oral
      gavage (po) for a period of 6 weeks. Phase 2 consisted of dividing rats into 4
      groups ( n = 40 per group) and administering one of the following for 26 weeks to
      identify putative tumor promoters: (1) vehicle po, (2) 25 mg/kg/day rosiglitazone
      po, (3) 5% dietary sodium l-ascorbate, and (4) 3% dietary uracil. Rats were
      necropsied after 7.5 months, and urinary bladders were evaluated by
      histopathology. BBN/vehicle treatments induced the development of urothelial
      hyperplasia (83%) and papillomas (15%) but no transitional cell carcinomas
      (TCCs). Rosiglitazone increased the incidence and severity of papillomas (93%)
      and resulted in TCC in 10% of treated rats. Uracil was the most effective tumor
      promoter in our study and increased the incidence of papillomas (90%) and TCC
      (74%). Sodium ascorbate decreased the incidence of urothelial hyperplasia (63%)
      and did not increase the incidence of urothelial papillomas or TCC. These data
      confirm the capacity of our 2-stage model to identify urinary bladder tumor
      promoters.

PMID- 29471779
TI  - Characterizing Adversity of Lysosomal Accumulation in Nonclinical Toxicity
      Studies: Results from the 5th ESTP International Expert Workshop.
AB  - Lysosomes have a central role in cellular catabolism, trafficking, and processing
      of foreign particles. Accumulation of endogenous and exogenous materials in
      lysosomes represents a common finding in nonclinical toxicity studies.
      Histologically, these accumulations often lack distinctive features indicative of
      lysosomal or cellular dysfunction, making it difficult to consistently interpret
      and assign adverse dose levels. To help address this issue, the European Society
      of Toxicologic Pathology organized a workshop where representative types of
      lysosomal accumulation induced by pharmaceuticals and environmental chemicals
      were presented and discussed. The expert working group agreed that the diversity
      of lysosomal accumulations requires a case-by-case weight-of-evidence approach
      and outlined several factors to consider in the adversity assessment, including
      location and type of cell affected, lysosomal contents, severity of the
      accumulation, and related pathological effects as evidence of cellular or organ
      dysfunction. Lysosomal accumulations associated with cytotoxicity, inflammation,
      or fibrosis were generally considered to be adverse, while those found in
      isolation (without morphologic or functional consequences) were not. Workshop
      examples highlighted the importance of thoroughly characterizing the biological
      context of lysosomal effects, including mechanistic data and functional in vitro
      readouts if available. The information provided here should facilitate greater
      consistency and transparency in the interpretation of lysosomal effects.

PMID- 29471780
TI  - How large B-factors can be in protein crystal structures.
AB  - BACKGROUND: Protein crystal structures are potentially over-interpreted since
      they are routinely refined without any restraint on the upper limit of atomic B
      factors. Consequently, some of their atoms, undetected in the electron density
      maps, are allowed to reach extremely large B-factors, even above 100 square
      Angstroms, and their final positions are purely speculative and not based on any
      experimental evidence. RESULTS: A strategy to define B-factors upper limits is
      described here, based on the analysis of protein crystal structures deposited in
      the Protein Data Bank prior 2008, when the tendency to allow B-factor to
      arbitrary inflate was limited. This B-factor upper limit (B_max) is determined by
      extrapolating the relationship between crystal structure average B-factor and
      percentage of crystal volume occupied by solvent (pcVol) to pcVol =100%, when, ab
      absurdo, the crystal contains only liquid solvent, the structure of which is, by
      definition, undetectable in electron density maps. CONCLUSIONS: It is thus
      possible to highlight structures with average B-factors larger than B_max, which
      should be considered with caution by the users of the information deposited in
      the Protein Data Bank, in order to avoid scientifically deleterious over
      interpretations.

PMID- 29471781
TI  - Solid lipid curcumin particles provide greater anti-amyloid, anti-inflammatory
      and neuroprotective effects than curcumin in the 5xFAD mouse model of Alzheimer's
      disease.
AB  - BACKGROUND: Neuroinflammation and the presence of amyloid beta protein (Abeta)
      and neurofibrillary tangles are key pathologies in Alzheimer's disease (AD). As a
      potent anti-amyloid and anti-inflammatory natural polyphenol, curcumin (Cur)
      could be potential therapies for AD. Unfortunately, poor solubility, instability
      in physiological fluids, and low bioavailability limit its clinical utility.
      Recently, different lipid modifications in the formulae of Cur have been
      developed that would enhance its therapeutic potential. For example, we have
      reported greater permeability and neuroprotection with solid lipid curcumin
      particles (SLCP) than with natural Cur in an in vitro model of AD. In the present
      study, we compared the Abeta aggregation inhibition, anti-amyloid, anti
      inflammatory responses of Cur and or SLCP in both in vitro and in vivo models of
      AD. One-year-old 5xFAD-and age-matched wild-type mice were given intraperitoneal
      injections of Cur or SLCP (50 mg/kg body weight) for 2- or 5-days. Levels of
      Abeta aggregation, including oligomers and fibril formation, were assessed by dot
      blot assay, while Abeta plaque load and neuronal morphology in the pre-frontal
      cortex (PFC) and hippocampus were assayed by immunolabeling with Abeta-specific
      antibody and cresyl violet staining, respectively. In addition, neuroinflammation
      was assessed the immunoreactivity (IR) of activated astrocytes (GFAP) and
      microglia (Iba-1) in different brain areas. Finally, comparisons of solubility
      and permeability of Cur and SLCP were made in cultured N2a cells and in primary
      hippocampal neurons derived from E16 pups of 5xFAD mice. RESULTS: We observed
      that relative to Cur, SLCP was more permeable, labeled Abeta plaques more
      effectively, and produced a larger decrease in Abeta plaque loads in PFC and
      dentate gyrus (DG) of hippocampus. Similarly, relative to Cur, SLCP produced a
      larger decrease of pyknotic, or tangle-like, neurons in PFC, CA1, and CA3 areas
      of hippocampus after 5 days of treatment. Both Cur and or SLCP significantly
      reduced GFAP-IR and Iba-1-IR in PFC, in the striatum as well as CA1, CA3, DG,
      subicular complex of hippocampus, and the entorhinal cortex in the 5xFAD mice
      after 5 days of treatment. CONCLUSIONS: The use of SLCP provides more anti
      amyloid, anti-inflammatory, and neuroprotective outcomes than does Cur in the
      5xFAD mouse model of AD.

PMID- 29471782
TI  - Transcapillary fluid flux and inflammatory response during neonatal therapeutic
      hypothermia: an open, longitudinal, observational study.
AB  - BACKGROUND: Therapeutic hypothermia is neuroprotective in asphyxiated neonates by
      counteracting mechanisms contributing to brain injury. Although an initial
      increased permeability is part of an inflammatory reaction and thereby a natural
      healing process, an excessive endothelial permeability with edema formation may
      result in impaired hemodynamics. Reduced permeability may, however, benefit
      healing. Although plasma and interstitial colloid osmotic pressure are accessible
      and essential parameters for understanding fluid imbalance, the mechanisms of
      fluid exchange remain poorly understood. The potential influence of therapeutic
      hypothermia on plasma and interstitial colloid osmotic pressure, and the
      relationship between inflammatory markers and colloid osmotic pressure in
      asphyxiated neonates, was investigated. METHODS: Seventeen neonates with moderate
      to severe hypoxic ischemic encephalopathy, born after 35 weeks gestation,
      received servo-controlled whole body cooling before 6 h of age, followed by
      gradual rewarming after 72 h. All infants were treated according to a national
      hypothermia protocol. Interstitial fluid in the skin was collected at 7, 13, 25,
      49, and 73 h after birth by subcutaneous implantation of multifilamentous nylon
      wicks with 60 min of implantation time. Biomarkers of inflammation and colloid
      osmotic pressure were measured in serum and interstitial fluid. RESULTS: A modest
      decrease in serum and interstitial colloid osmotic pressure was measured, leaving
      an unaltered difference in colloid osmotic pressure gradient. A decline in mean
      arterial pressure was observed between 7 and 13 h of life, with a concomitant
      decrease in positive fluid balance within the same time frame. White blood cell
      count and leukocyte subclasses dropped significantly throughout treatment, with
      elevated interstitial interleukin (IL)-1alpha and decreased serum IL-1RA, IL-6,
      and IL-10 during treatment time points. CONCLUSIONS: Colloid osmotic pressures
      measured in serum and interstitial fluid during asphyxia is lower than previously
      reported, with small alteration of pressure differences across capillaries,
      reducing vascular filtration. An inherent local and systemic regulation of
      inflammation together with changes in colloid osmotic pressure may indicate a
      possible preventive mechanism of edema generation during neonatal asphyxia and
      therapeutic hypothermia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01044940 . Date of registration: January 8, 2010.

PMID- 29471783
TI  - Seroprevalence of dengue IgG antibodies in symptomatic and asymptomatic
      individuals three years after an outbreak in Zhejiang Province, China.
AB  - BACKGROUND: Cross-reacting antibodies enhanced dengue infection in humans and
      antibody dependent enhancement (ADE) have been proposed as early mechanisms
      underlying DHF/DSS. However, the duration of dengue IgG antibodies in the body as
      well as factors associated with said duration remain unclear. METHODS: Blood
      samples from 59 dengue symptomatic persons and 48 asymptomatic individuals were
      collected. Study participant demographic information (including age in 2009,
      gender, and place of residence) were also collected. Serum samples were tested
      for dengue specific IgG by Panbio dengue IgG indirect enzyme-linked immunosorbent
      assay (ELISA). Chi-square tests and logistic regression analysis of dengue IgG
      antibodies seroprevalence divided by gender, age groups, and symptomatic or
      asymptomatic infection were conducted using the Statistical Package for the
      Social Sciences. RESULTS: Overall, 70 (65.42%) blood samples were seropositive
      for dengue IgG antibodies with similar seroprevalences found when dividing by
      gender and different age groups. However, seroprevalence of dengue IgG antibodies
      in samples from dengue symptomatic persons was significantly higher than that in
      samples from asymptomatic individuals (96.61% vs 27.08%) according to
      multivariable logistic regression analysis, the odds ratio (OR) of the factor was
      76.731. CONCLUSIONS: Dengue IgG antibodies were detectable in samples from most
      individuals three years after infection. Dengue symptomatic persons had a higher
      dengue IgG prevalence compared to asymptomatic individuals.

PMID- 29471784
TI  - Potential cost savings to be made by slowing cognitive decline in mild
      Alzheimer's disease dementia using a model derived from the UK GERAS
      observational study.
AB  - BACKGROUND: Given the high costs associated with the care of those with
      Alzheimer's disease (AD) dementia, we examined the likely impact of a reduction
      in the rate of cognitive decline upon cost outcomes associated with this disease.
      METHODS: Using the group of patients with mild AD dementia from the GERAS study,
      generalised linear modelling (GLM) was used to explore the relationship between
      change in cognition as measured using the Mini-Mental State Examination (MMSE)
      and UK overall costs (health care and social care costs, and total societal
      costs) associated with AD dementia. RESULTS: A total of 200 patients with mild AD
      dementia were identified. Least squares mean (LSM) +/- standard error (SE)
      reduction in MMSE score was 3.6 +/- 0.4 points over 18 months. Using GLM it was
      possible to calculate that this worsening in cognition was associated with an
      8.7% increase in total societal costs, equating to an increase of approximately
      L2200 per patient over an 18-month period. If the rate of decline in cognition
      was reduced by 30% or 50%, the associated savings in total societal costs over 18
      months would be approximately L670 and L1100, respectively, of which only L110
      and L180, respectively, could be attributed to a saving of health care costs.
      CONCLUSION: This study demonstrates that there are potential savings to be made
      in the care of patients with AD dementia through reducing the rate of cognitive
      decline. A reduction in wider societal costs is likely to be the main contributor
      to these potential savings, and need to be further evaluated when intervention
      costs and cost offsets can be measured.

PMID- 29471785
TI  - Phylogeny with introgression in Habronattus jumping spiders (Araneae:
      Salticidae).
AB  - BACKGROUND: Habronattus is a diverse clade of jumping spiders with complex
      courtship displays and repeated evolution of Y chromosomes. A well-resolved
      species phylogeny would provide an important framework to study these traits, but
      has not yet been achieved, in part because the few genes available in past
      studies gave conflicting signals. Such discordant gene trees could be the result
      of incomplete lineage sorting (ILS) in recently diverged parts of the phylogeny,
      but there are indications that introgression could be a source of conflict.
      RESULTS: To infer Habronattus phylogeny and investigate the cause of gene tree
      discordance, we assembled transcriptomes for 34 Habronattus species and 2
      outgroups. The concatenated 2.41 Mb of nuclear data (1877 loci) resolved
      phylogeny by Maximum Likelihood (ML) with high bootstrap support (95-100%) at
      most nodes, with some uncertainty surrounding the relationships of H. icenoglei,
      H. cambridgei, H. oregonensis, and Pellenes canadensis. Species tree analyses by
      ASTRAL and SVDQuartets gave almost completely congruent results. Several nodes in
      the ML phylogeny from 12.33 kb of mitochondrial data are incongruent with the
      nuclear phylogeny and indicate possible mitochondrial introgression: the internal
      relationships of the americanus and the coecatus groups, the relationship between
      the altanus, decorus, banksi, and americanus group, and between H. clypeatus and
      the coecatus group. To determine the relative contributions of ILS and
      introgression, we analyzed gene tree discordance for nuclear loci longer than 1
      kb using Bayesian Concordance Analysis (BCA) for the americanus group (679 loci)
      and the VCCR clade (viridipes/clypeatus/coecatus/roberti groups) (517 loci) and
      found signals of introgression in both. Finally, we tested specifically for
      introgression in the concatenated nuclear matrix with Patterson's D statistics
      and DFOIL. We found nuclear introgression resulting in substantial admixture
      between americanus group species, between H. roberti and the clypeatus group, and
      between the clypeatus and coecatus groups. CONCLUSIONS: Our results indicate that
      the phylogenetic history of Habronattus is predominantly a diverging tree, but
      that hybridization may have been common between phylogenetically distant species,
      especially in subgroups with complex courtship displays.

PMID- 29471786
TI  - Dengue score as a diagnostic predictor for pleural effusion and/or ascites:
      external validation and clinical application.
AB  - BACKGROUND: The Dengue Score is a model for predicting pleural effusion and/or
      ascites and uses the hematocrit (Hct), albumin concentration, platelet count and
      aspartate aminotransferase (AST) ratio as independent variables. As this metric
      has not been validated, we conducted a study to validate the Dengue Score and
      assess its clinical application. METHODS: A retrospective study was performed at
      a private hospital in Jakarta, Indonesia. Patients with dengue infection
      hospitalized from January 2011 through March 2016 were included. The Dengue Score
      was calculated using four parameters: Hct increase>=15.1%, serum albumin<=3.49
      mg/dL, platelet count<=49,500/MUL and AST ratio >= 2.51. Each parameter was
      scored as 1 if present and 0 if absent. To validate the Dengue Score, goodness-of
      fit was used to assess calibration, and the area under the receiver operating
      characteristic curve (AROC) was used to assess discrimination. Associations
      between clinical parameters and Dengue Score groups were determined by bivariate
      analysis. RESULTS: A total of 207 patients were included in this study. The
      calibration of the Dengue Score was acceptable (Hosmer-Lemeshow test, p = 0.11),
      and the score's discriminative ability was good (AROC = 0.88 (95% CI: 0.83
      0.92)). At a cutoff of >=2, the Dengue Score had a positive predictive value
      (PPV) of 79.03% and a negative predictive value (NPV) of 90.36% for the
      diagnostic prediction of pleural effusion and/or ascites. Compared with the
      Dengue Score <= 1 group, the Dengue Score = 2 group was significantly associated
      with hemoconcentration> 20% (p = 0.029), severe thrombocytopenia (p = 0.029), and
      increased length of hospital stay (p = 0.003). Compared with the Dengue Score = 2
      group, the Dengue Score >= 3 group was significantly associated with
      hemoconcentration> 20% (p = 0.001), severe thrombocytopenia (p = 0.024), severe
      dengue (p = 0.039), and increased length of hospital stay (p = 0.011).
      CONCLUSION: The Dengue Score performed well and can be used in daily practice to
      help clinicians identify patients who have plasma leakage associated with severe
      dengue.

PMID- 29471787
TI  - Evolutionary and expression analyses of soybean basic Leucine zipper
      transcription factor family.
AB  - BACKGROUND: Soybean, a major legume crop native to East Asia, presents a wealth
      of resources for utilization. The basic leucine zipper (bZIP) transcription
      factors play important roles in various biological processes including
      developmental regulation and responses to environmental stress stimuli.
      Currently, little information is available regarding the bZIP family in the
      legume crop soybean. RESULTS: Using a genome-wide domain analysis, we identified
      160 GmbZIP genes in soybean genome, named from GmbZIP1 to GmbZIP160. These
      160GmbZIP genes, distributed unevenly across 20 chromosomes, were grouped into 12
      subfamilies based on phylogenetic analysis. Gene structure and conserved motif
      analyses showed that GmbZIP within the same subfamily shared similar intron-exon
      organizations and motif composition. Syntenic and phylogenetic analyses
      identified 40 Arabidopsis bZIP genes and 83 soybean bZIP genes as orthologs. By
      investigating the expression profiling of GmbZIP in different tissues and under
      drought and flooding stresses, we showed that a majority of GmbZIP (83.44%)
      exhibited transcript abundance in all examined tissues and 75.6% displayed
      transcript changes after drought and flooding treatment, suggesting that GmbZIP
      may play a broad role in soybean development and response to water stress.
      CONCLUSIONS: One hundred sixty GmbZIP genes were identified in soybean genome.
      Our results provide insights for the evolutionary history of bZIP family in
      soybean and shed light on future studies on the function of bZIP genes in
      response to water stress in soybean.

PMID- 29471788
TI  - Modelling physiological and pathological conditions to study pericyte biology in
      brain function and dysfunction.
AB  - BACKGROUND: Brain pericytes ensheathe the endothelium and contribute to formation
      and maintenance of the blood-brain-barrier. Additionally, pericytes are involved
      in several aspects of the CNS immune response including scarring, adhesion
      molecule expression, chemokine secretion, and phagocytosis. In vitro cultures are
      routinely used to investigate these functions of brain pericytes, however, these
      are highly plastic cells and can display differing phenotypes and functional
      responses depending on their culture conditions. Here we sought to investigate
      how two commonly used culture media, high serum containing DMEM/F12 and low serum
      containing Pericyte Medium (ScienCell), altered the phenotype of human brain
      pericytes and neuroinflammatory responses. METHODS: Pericytes were isolated from
      adult human brain biopsy tissue and cultured in DMEM/F12 (D-pericytes) or
      Pericyte Medium (P-pericytes). Immunocytochemistry, qRT-PCR, and EdU
      incorporation were used to determine how this altered their basal phenotype,
      including the expression of pericyte markers, proliferation, and cell morphology.
      To determine whether culture media altered the inflammatory response in human
      brain pericytes, immunocytochemistry, qRT-PCR, cytometric bead arrays, and flow
      cytometry were used to investigate transcription factor induction, chemokine
      secretion, adhesion molecule expression, migration, phagocytosis, and response to
      inflammatory-related growth factors. RESULTS: P-pericytes displayed elevated
      proliferation and a distinct bipolar morphology compared to D-pericytes.
      Additionally, P-pericytes displayed lower expression of pericyte-associated
      markers NG2, PDGFRbeta, and fibronectin, with notably lower alphaSMA, CD146, P4H
      and desmin, and higher Col-IV expression. Nuclear NF-kB translocation in response
      to IL-1beta stimulation was observed in both cultures, however, P-pericytes
      displayed elevated expression of the transcription factor C/EBPdelta, and lower
      expression of the adhesion molecule ICAM-1. P-pericytes displayed elevated
      phagocytic and migratory ability. Both cultures responded similarly to
      stimulation by the growth factors TGFbeta1 and PDGF-BB. CONCLUSIONS: Despite
      differences in their phenotype and magnitude of response, both P-pericytes and D
      pericytes responded similarly to all examined functions, indicating that the
      neuroinflammatory phenotype of these cells is robust to culture conditions.

PMID- 29471789
TI  - Melanin-embedded materials effectively remove hexavalent chromium (CrVI) from
      aqueous solution.
AB  - BACKGROUND: Currently, it is recognized that water polluted with toxic heavy
      metal ions may cause serious effects on human health. Therefore, the development
      of new materials for effective removal of heavy metal ions from water is still a
      widely important area. Melanin is being considered as a potential material for
      removal of heavy metal from water. METHODS: In this study, we synthesized two
      melanin-embedded beads from two different melanin powder sources and named IMB
      (Isolated Melanin Bead originated from squid ink sac) and CMB (Commercial Melanin
      Bead originated from sesame seeds). These beads were of globular shape and 2-3 mm
      in diameter. We investigated and compared the sorption abilities of these two
      bead materials toward hexavalent-chromium (CrVI) in water. The isotherm sorption
      curves were established using Langmuir and Freundlich models in the optimized
      conditions of pH, sorption time, solid/liquid ratio, and initial concentration of
      CrVI. The FITR analysis was also carried out to show the differences in surface
      properties of these two beads. RESULTS: The optimized conditions for isotherm
      sorption of CrVI on IMB/CMB were set at pH values of 2/2, sorption times of
      90/300 min, and solid-liquid ratios of 10/20 mg/mL. The maximum sorption
      capacities calculated based on the Langmuir model were 19.60 and 6.24 for IMB and
      CMB, respectively. However, the adsorption kinetic of CrVI on the beads fitted
      the Freundlich model with R2 values of 0.992 for IMB and 0.989 for CMB. The
      deduced Freundlich constant, 1/n, in the range of 0.2-0.8 indicated that these
      beads are good adsorption materials. In addition, structure analysis data
      revealed great differences in physical and chemical properties between IMB and
      CMB. Interestingly, FTIR analysis results showed strong signals of -OH (3295.35
      cm- 1) and -C=O (1608.63 cm- 1) groups harboring on the IMB but not CMB.
      Moreover, loading of CrVI on the IMB caused a shift of broad peaks from 3295.35
      cm- 1 and 1608.63 cm- 1 to 3354.21 cm- 1 and 1597.06 cm- 1, respectively, due to 
      OH and -C=O stretching. CONCLUSIONS: Taken together, our study suggests that IMB
      has great potential as a bead material for the elimination of CrVI from aqueous
      solutions and may be highly useful for water treatment applications.

PMID- 29471790
TI  - Gene expression correlated with delay in shell formation in larval Pacific
      oysters (Crassostrea gigas) exposed to experimental ocean acidification provides
      insights into shell formation mechanisms.
AB  - BACKGROUND: Despite recent work to characterize gene expression changes
      associated with larval development in oysters, the mechanism by which the larval
      shell is first formed is still largely unknown. In Crassostrea gigas, this shell
      forms within the first 24 h post fertilization, and it has been demonstrated that
      changes in water chemistry can cause delays in shell formation, shell
      deformations and higher mortality rates. In this study, we use the delay in shell
      formation associated with exposure to CO2-acidified seawater to identify genes
      correlated with initial shell deposition. RESULTS: By fitting linear models to
      gene expression data in ambient and low aragonite saturation treatments, we are
      able to isolate 37 annotated genes correlated with initial larval shell
      formation, which can be categorized into 1) ion transporters, 2) shell matrix
      proteins and 3) protease inhibitors. Clustering of the gene expression data into
      co-expression networks further supports the result of the linear models, and also
      implies an important role of dynein motor proteins as transporters of cellular
      components during the initial shell formation process. CONCLUSIONS: Using an RNA
      Seq approach with high temporal resolution allows us to identify a conceptual
      model for how oyster larval calcification is initiated. This work provides a
      foundation for further studies on how genetic variation in these identified genes
      could affect fitness of oyster populations subjected to future environmental
      changes, such as ocean acidification.

PMID- 29471791
TI  - Systemic fluoroquinolone prescriptions for hospitalized children in Belgium,
      results of a multicenter retrospective drug utilization study.
AB  - BACKGROUND: Fluoroquinolones (FQ) are increasingly prescribed for children,
      despite being labeled for only a limited number of labeled pediatric indications.
      In this multicenter retrospective drug utilization study, we analyzed indications
      for systemic FQ prescriptions in hospitalized children and the appropriateness of
      the prescribed dose. METHODS: Using data obtained from electronic medical files,
      the study included all children who received a systemic FQ prescription in two
      Belgian university children's hospitals between 2010 and 2013. Two authors
      reviewed prescribed daily doses. Univariate and multivariate logistic regression
      models were used to analyze risk factors for inadequately dosing. Results262 FQ
      prescriptions for individual patients were included for analysis. 16.8% of these
      prescriptions were for labeled indications, and 35.1% were guided by
      bacteriological findings. Prescribed daily dose was considered to be
      inappropriate in 79 prescriptions (30.2%). Other FQ than ciprofloxacin accounted
      for 9 prescriptions (3.4%), of which 8 were correctly dosed. Underdosing
      represented 45 (56.9%) dosing errors. Infants and preschool children were at
      particular risk for dosing errors, with associated adjusted OR of 0.263 (0.097
      0.701) and 0.254 (0.106-0.588) respectively. CONCLUSIONS: FQ were often
      prescribed off-label and not guided by bacteriological findings in our study
      population. Dosing errors were common, particularly in infants and preschool
      children. FQ prescriptions for children should be improved by specific pediatric
      antimicrobial stewardship teams. Furthermore, pharmacokinetic studies should
      optimise dosing recommendations for children.

PMID- 29471792
TI  - Inpatient falls in older adults: a cohort study of antihypertensive prescribing
      pre- and post-fall.
AB  - BACKGROUND: Falls are common during hospital admissions and may occur more
      frequently in patients who are taking antihypertensive medications, particularly
      in the context of normal to low blood pressure. The review and adjustment of
      these medications is an essential aspect of the post-fall assessment and should
      take place as soon as possible after the fall. Our aim was to investigate whether
      appropriate post-fall adjustments of antihypertensive medications are routinely
      made in a large National Health Service (NHS) Trust. METHODS: Inpatient records
      over an eight-month period were captured from an electronic prescribing system to
      identify older adults (>=80 years old) with normal/low blood pressures (< 140
      mmHg systolic) who had a documented inpatient fall as these patients were
      considered to be at high risk of further falls. Prescribed antihypertensive
      medication on admission was then compared with the post-fall (within 24 h after
      the fall) and discharge prescriptions. RESULTS: A total of 146 patients were
      included in the analysis. Of those, 120 patients (82%) were taking the same
      number of antihypertensive medications in the 24 h after the fall as they were
      before; only 19 patients (13%) had a reduction in the number of medications and
      seven patients (5%) had an increase in medications during that period. Only 9% of
      the antihypertensive classes assessed were either stopped or reduced in dose
      immediately post-fall. In addition, 11 new antihypertensives were prescribed at
      this time. At discharge, half of the patients (n = 73) remained on the same
      number of antihypertensive medication as on admission, 51 patients (35%) were on
      fewer antihypertensives and 22 (15%) were on more. Additionally, no changes were
      made to individual antihypertensives in 49% of prescriptions; 34% were stopped or
      reduced in dose but 38 new agents were started by the time of discharge.
      Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers
      (ACEi/ARB) were the class of medications most commonly stopped or reduced (51%).
      CONCLUSIONS: Antihypertensive prescriptions are frequently unchanged after an
      inpatient fall. Routine medication review needs to be part of post-fall
      assessments in hospital to reduce the risk of further falls.

PMID- 29471793
TI  - Factors associated with the time to cessation of breastfeeding among mothers who
      have index children aged two to three years in Debre Markos, northwest Ethiopia:
      a retrospective follow up study.
AB  - BACKGROUND: Breastfeeding of children, which needs to continue until two years
      and beyond, is one of the essential requirements for child survival. However, in
      Ethiopia there is scarcity of literatures on the duration of breastfeeding.
      Therefore, the aim of this study was to assess the rate of cessation of
      breastfeeding among mothers with index children aged 2 to 3 years, northwest
      Ethiopia. METHODS: A retrospective follow-up study was conducted at Debre Markos
      town from March 1, 2014 to March 30, 2016. A total of 500 mother-child pairs were
      selected using the systematic random sampling method by moving from house to
      house with an interval of three eligible houses. A structured questionnaire was
      used to collect data. The Cox regression model was employed to identify the
      predictors of breastfeeding cessation. RESULTS: The proportion of women
      breastfeeding until 2 years was 13.70 per 1000 person- months. HIV-positive
      mothers decreased the time of breastfeeding by 3.4 times compared to HIV-negative
      mothers (AHR = 3.41, 95% CI: 1.96, 5.94). Government employee mothers decreased
      the time of breastfeeding by 2.8 times compared to housewives (AHR = 2.8, 95% CI:
      1.80, 4.40).Better education increased the time of breastfeeding (AHR = 0.45, 95%
      CI: 0.24, 0.58). Number of children, family income, and place of delivery were
      the other significant predictors of time to cessation of breastfeeding (p <
      0.05). CONCLUSION: In this study, the rate of cessation of breastfeeding was
      good. HIV negative mothers, government employment, number of children, place of
      delivery, and family monthly income were significant predictors to the time of
      breastfeeding cessation. Therefore, family planning and breastfeeding education
      in health institutions are essential to increase breastfeeding duration.

PMID- 29471794
TI  - LGR5 overexpression confers poor relapse-free survival in breast cancer patients.
AB  - BACKGROUND: Cancer stem cells (CSCs) are believed to promote the malignant
      transformation of breast cancer via multiple signaling pathways, including the
      Wnt/beta-catenin pathway. Leucine-rich repeat-containing G protein-coupled
      receptor 5 (LGR5) has been identified as a CSC-associated Wnt-regulated target
      gene, but its clinical significance in the context of breast cancer remains
      elusive. Therefore, the purpose of this study was to investigate the clinical
      significance of the LGR5-beta-catenin axis in breast cancer. METHODS: Breast
      cancer tissue blocks from 126 patients were used to construct a tissue microarray
      (TMA). Histopathological and clinical data including age; tumor size; estrogen
      receptor (ER), progesterone receptor (PR), and human epidermal growth factor
      receptor 2 (HER2) level; tumor grade; lymph node (LN) status; and survival were
      obtained from the cancer registry database and patients' medical records. Tissue
      on the breast TMA was scored for LGR5 and beta-catenin expression using semi
      quantitative immunohistochemical (IHC) staining. We also analyzed LGR5 expression
      in cellular datasets available through ONCOMINE, a web-based cancer microarray
      database. RESULTS: Immunohistochemical staining revealed that 58 tumors (46%)
      exhibited high LGR5 expression, whereas 56 tumors (47%) displayed high beta
      catenin expression. High levels of LGR5 expression were significantly associated
      with tumor size (p = 0.002), LN metastasis status (p = 0.044), and triple
      negative breast cancer (p = 0.029), consistent with our findings from the
      ONCOMINE database. In addition, we also found that beta-catenin -expressing
      breast cancers were positive correlated with HER2 overexpression. Finally, with
      respect to clinical outcomes, patients with high levels of LGR5-beta-catenin axis
      expression exhibited poorer relapse-free survival (RFS) compared to patients with
      low levels of LGR5-beta-catenin axis expression (p = 0.027). CONCLUSION: LGR5
      overexpression was significantly associated with high T stage and LN metastasis
      status. High LGR5 expression was also associated with reduced RFS, indicating
      that LGR5 may represent a promising prognostic marker for breast cancer patients.

PMID- 29471795
TI  - Superficial punctate keratopathy in a pediatric patient was related to adenoid
      hypertrophy and obstructive sleep apnea syndrome: a case report.
AB  - BACKGROUND: Known causes of superficial punctuate keratopathy (SPK) in children
      include entropion, viral infection, blepharokeratoconjunctivitis (BKC), and
      toxicity of eye drops. However, there are some SPK patients whose causes could
      not be identified well. Herein, we describe the history, diagnosis, treatment,
      and prognosis of a rare case. CASE PRESENTATION: To report a case of superficial
      punctate keratopathy (SPK) which coexisted with floppy eyelid syndrome (FES) and
      presented as intermittent red eye and blurred vision in an 11-year-old boy who
      slept in the prone position. His condition did not improve despite treatment with
      topical antibiotics (levofloxacin, tobramycin), steroid eye drops (prednisolone),
      and artificial tears. The patient was diagnosed with tonsil hypertrophy and
      nasopharyngeal adenoid hypertrophy and obstructive sleep apnea syndrome (OSAS).
      He underwent tonsillectomy and adenoidectomy. Then he started sleeping in the
      supine position postoperatively. The SPK, red eye and blurred vision completely
      resolved after surgery without additional treatment. The corneal sensation also
      recovered gradually during the next 7 years. However, the floppy eyelid did not
      resolve. CONCLUSION: Recurrent SPK of childhood might be related to tonsil
      hypertrophy, adenoid hypertrophy and OSAS, which can be rehabilitated by a
      surgical approach.

PMID- 29471796
TI  - Impact of pulsed xenon ultraviolet disinfection on surface contamination in a
      hospital facility's expressed human milk feed preparation area.
AB  - BACKGROUND: Expressed human milk (EHM) feed preparation areas represent a
      potential source of unintentional nosocomial infection. Daily disinfection of
      environmental surfaces remains an essential intervention to mitigate nosocomial
      infections. The inefficiency of conventional cleaning and disinfection
      contributes to an increased risk for the acquisition of multi-drug resistant
      pathogens. "Non touch" technologies such as the pulsed xenon ultraviolet (PX-UVD)
      light device have documented sustained reduction in surface bacterial
      colonization and reduced cross contamination. METHODS: The impact of a PX-UVD on
      surface colony forming units per square centimeter (cfu/cm2) in feed preparation
      areas was evaluated following its implementation as standard care. A quasi
      experimental study was performed documenting bacterial colonization from 6 high
      risk feed preparation areas in a community care hospital in South Africa. Pre and
      post conventional cleaning neutralizing rinse swabs were collected fortnightly
      over a 16 week control period prior to the introduction of the PX-UVD and
      compared to a matching set of samples for the PX-UVD period. RESULTS: A 90%
      reduction in total surface bioburden was noted from the control period (544
      cfu/cm2) compared to the corresponding PX-UVD period (50 cfu/cm2). Sub -analysis
      of both the Pre-clean Control: Pre-clean PX-UVD counts as well as the Post-clean
      Control: Post-clean PX-UVD counts noted significant improvements (p < 0.001). A
      statistically significant improvement was noted between pre-and post-cleaning
      total surface bioburden following exposure to the PX-UVD (p = 0.0004). The
      introduction of the PX-UVD was associated with a sustained reduction in the pre
      clean bioburden counts with a risk trend (per week) 0.19, (95% CI [0.056, 0.67],
      p = 0.01). DISCUSSION: The use of a PX-UVD as adjunct to standard cleaning
      protocols was associated with a significant decrease in surface bioburden. The
      study demonstrated the inefficiency of conventional cleaning. Persistence of
      potentially pathological species in both periods highlights current health sector
      challenges.

PMID- 29471797
TI  - Exercise reduces body fat and improves insulin sensitivity and pancreatic beta
      cell function in overweight and obese male Taiwanese adolescents.
AB  - BACKGROUND: Improvements in insulin resistance and pancreatic beta-cell function
      have been shown following exercise in adults with obesity; however, few
      adolescent-based studies have been conducted. This study examined the impact of
      exercise training on body fat and insulin sensitivity and secretion in overweight
      and obese adolescents. METHODS: The effects of a 12-week exercise program on the
      parameters of adiposity and glucose homeostasis were investigated in 47
      overweight and obese male adolescents. RESULTS: After the exercise training
      program, body weight, body mass index, waist circumference, and body fat were
      significantly decreased (P < 0.001). Improvements in insulin sensitivity (HOMA
      IR: 1.40 vs. 0.86, P < 0.001) and the disposition index (5.84 vs. 12.77, P <
      0.001) were also observed. Compared to baseline, oral glucose tolerance tests
      showed reduced glucose and insulin levels at all time points following the
      exercise training (all P < 0.001). Subgroup analysis of overweight and obese
      adolescents with abnormal glucose tolerance revealed that there was no difference
      in plasma glucose levels as compared to the lean group. CONCLUSIONS: A 12-week
      exercise training is effective in reducing body fat and improving insulin
      sensitivity and secretion. In addition, the benefits of the exercise intervention
      were even experienced by those with impaired glucose tolerance.

PMID- 29471798
TI  - Different patterns of myopia prevalence and progression between internal migrant
      and local resident school children in Shanghai, China: a 2-year cohort study.
AB  - BACKGROUND: In 2010, there were ~ 36 million migrant children under 18 y old in
      China. This study compared patterns of myopia prevalence and progression between
      migrant and resident children. METHODS: Eight hundred forty-two migrant children
      from 2 migrant schools and 1081 from 2 local schools in Baoshan District,
      Shanghai, were randomly chosen. Baseline measurements were taken on children in
      grades one through four, and children in grades one and two were followed for 2
      y. The children underwent comprehensive ophthalmic examinations, including
      cycloplegic refraction and axial length. The average time per week spent on
      homework and outdoor activities were investigated. RESULTS: Migrant children in
      grades one and two showed a lower myopia prevalence than resident children;
      however, from grades three to four, the prevalence accelerated and exceeded that
      of residents. In the follow-up, the myopia incidence did not significantly change
      from grades one to two in resident children but was significantly higher in grade
      two in migrant children. Correspondingly, for migrant children, increased
      progression of refraction and axial length was observed; however, it decreased in
      resident children. The average time spent on homework increased from grades two
      to three in parallel with the acceleration of myopia prevalence for migrant
      children; however, the time spent outdoors did not correspondingly change.
      CONCLUSION: The patterns of myopia prevalence and progression are different
      between migrant and non-migrant children. The acceleration of myopia in migrant
      children might be a result of a change in their environment, such as intensive
      education pressure.

PMID- 29471800
TI  - Correction to: An audit of clinical training exposure amongst junior doctors
      working in Trauma & Orthopaedic Surgery in 101 hospitals in the United Kingdom.
AB  - CORRECTION: Following publication of the original article [1], the corresponding
      author wrote to say that he had missed the names of some of the collaborators in
      the list he sent to the typesetters. In addition, there was a spelling error in
      one of the author's names: instead of Nagriz Seyidova it should read Nargiz
      Seyidova. The complete list of collaborators is as follows.

PMID- 29471799
TI  - "Not just another Wii training": a graded Wii protocol to increase physical
      fitness in adolescent girls with probable developmental coordination disorder-a
      pilot study.
AB  - BACKGROUND: Adolescents with low motor competence participate less in physical
      activity and tend to exhibit decreased physical fitness compared to their peers
      with high motor competence. It is therefore essential to identify new methods of
      enhancing physical fitness in this population. Active video games (AVG) have been
      shown to improve motor performance, yet investigations of its impact on physical
      fitness are limited. The objective of this study was to examine the impact of the
      graded Wii protocol in adolescent girls with probable Developmental Coordination
      Disorder (p-DCD). METHODS: A single-group pre-post design was conducted to assess
      the impact of a newly developed Wii protocol in adolescent girls attending school
      in a low income community of Cape Town, South Africa. Sixteen participants (aged
      13-16 years) with p-DCD (<=16th percentile on the MABC-2 test) were recruited.
      Participants received 45 min Wii training for 14 weeks. Outcome measures included
      the six-minute walk distance and repeated sprint ability. Information on heart
      rate, enjoyment and perceived exertion ratings were also collected. RESULTS:
      Significant improvements in aerobic and anaerobic fitness were observed. The
      participants reported high enjoyment scores and low perceived exertion ratings.
      The graded Wii protocol was easily adaptable and required little resources
      (space, equipment and expertise) to administer. CONCLUSIONS: The findings provide
      preliminary evidence to support the use of the graded Wii protocol for promoting
      physical fitness in adolescent girls with p-DCD. Further studies are needed to
      confirm these results and to validate the clinical efficacy of the protocol in a
      larger sample with a more robust design.

PMID- 29471801
TI  - A maximum likelihood algorithm for reconstructing 3D structures of human
      chromosomes from chromosomal contact data.
AB  - BACKGROUND: The development of chromosomal conformation capture techniques,
      particularly, the Hi-C technique, has made the analysis and study of the spatial
      conformation of a genome an important topic in bioinformatics and computational
      biology. Aided by high-throughput next generation sequencing techniques, the Hi-C
      technique can generate genome-wide, large-scale intra- and inter-chromosomal
      interaction data capable of describing in details the spatial interactions within
      a genome. These data can be used to reconstruct 3D structures of chromosomes that
      can be used to study DNA replication, gene regulation, genome interaction, genome
      folding, and genome function. RESULTS: Here, we introduce a maximum likelihood
      algorithm called 3DMax to construct the 3D structure of a chromosome from Hi-C
      data. 3DMax employs a maximum likelihood approach to infer the 3D structures of a
      chromosome, while automatically re-estimating the conversion factor (alpha) for
      converting Interaction Frequency (IF) to distance. Our results show that the
      models generated by 3DMax from a simulated Hi-C dataset match the true models
      better than most of the existing methods. 3DMax is more robust to structural
      variability and noise. Compared on a real Hi-C dataset, 3DMax constructs
      chromosomal models that fit the data better than most methods, and it is faster
      than all other methods. The models reconstructed by 3DMax were consistent with
      fluorescent in situ hybridization (FISH) experiments and existing knowledge about
      the organization of human chromosomes, such as chromosome compartmentalization.
      CONCLUSIONS: 3DMax is an effective approach to reconstructing 3D chromosomal
      models. The results, and the models generated for the simulated and real Hi-C
      datasets are available here: http://sysbio.rnet.missouri.edu/bdm_download/3DMax/
      . The source code is available here: https://github.com/BDM-Lab/3DMax . A short
      video demonstrating how to use 3DMax can be found here:
      https://youtu.be/ehQUFWoHwfo .

PMID- 29471802
TI  - The short-term economic burden of gestational diabetes mellitus in Italy.
AB  - BACKGROUND: The incidence of Gestational Diabetes Mellitus (GDM) is rising in all
      developed countries. This study aimed at assessing the short-term economic burden
      of GDM from the Italian healthcare system perspective. METHODS: A model was built
      over the last pregnancy trimester (i.e., from the 28th gestational week until
      childbirth included). The National Hospital Discharge Database (2014) was
      accessed to estimate delivery outcome probabilities and inpatient costs in GDM
      and normal pregnancies (i.e., euglycemia). International Classification of
      Disease-9th Revision-Clinical Modification (ICD9-CM) diagnostic codes and
      Diagnosis-Related Group (DRG) codes were used to identify GDM cases and different
      types of delivery (i.e., vaginal or cesarean) within the database. Neonatal
      outcomes probabilities were estimated from the literature and included
      macrosomia, hypoglycemia, hyperbilirubinemia, shoulder dystocia, respiratory
      distress, and brachial plexus injury. Additional data sources such as regional
      documents, official price and tariff lists, national statistics and expert
      opinion were used to populate the model. The average cost per case was calculated
      at national level to estimate the annual economic burden of GDM. One-way
      sensitivity analyses and Monte Carlo simulations were performed to quantify the
      uncertainty around base case results. RESULTS: The amount of pregnancies
      complicated by GDM in Italy was assessed at 54,783 in 2014 using a prevalence
      rate of 10.9%. The antenatal outpatient cost per case was estimated at ?43.7 in
      normal pregnancies compared to ?370.6 in GDM patients, which is equivalent to a
      weighted sum of insulin- (14%; ?1034.6) and diet- (86%; ?262.5) treated women's
      costs. Inpatient delivery costs were assessed at ?1601.6 and ?1150.3 for
      euglycemic women and their infants, and at ?1835.0 and ?1407.7 for GDM women and
      their infants, respectively. Thus, the overall cost per case difference between
      GDM and normal pregnancies was equal to ?817.8 (+ 29.2%), resulting in an
      economic burden of about ?44.8 million in 2014 at national level. Probabilistic
      sensitivity analysis yielded a cost per case difference ranging between ?464.9
      and ?1164.8 in 80% of simulations. CONCLUSIONS: The economic burden of GDM in
      Italy is substantial even accounting for short-term medical costs only. Future
      research also addressing long-term consequences from a broader societal
      perspective is recommended.

PMID- 29471803
TI  - Divergence and evolution of cotton bHLH proteins from diploid to allotetraploid.
AB  - BACKGROUND: Polyploidy is considered a major driving force in genome expansion,
      yielding duplicated genes whose expression may be conserved or divergence as a
      consequence of polyploidization. RESULTS: We compared the genome sequences of
      tetraploid cotton (Gossypium hirsutum) and its two diploid progenitors, G.
      arboreum and G. raimondii, and found that the bHLH genes were conserved over the
      polyploidization. Oppositely, the expression of the homeolgous gene pairs was
      diversified. The biased homeologous proportion for bHLH family is significantly
      higher (64.6%) than the genome wide homeologous expression bias (40%). Compared
      with cacao (T. cacao), orthologous genes only accounted for a small proportion
      (41.7%) of whole cotton bHLHs family. The further Ks analysis indicated that bHLH
      genes underwent at least two distinct episodes of whole genome duplication: a
      recent duplication (1.0-60.0 million years ago, MYA, 0.005 < Ks < 0.312) and an
      old duplication (> 60.0 MYA, 0.312 < Ks < 3.0). The old duplication event might
      have played a key role in the expansion of the bHLH family. Both recent and old
      duplicated pairs (68.8%) showed a divergent expression profile, indicating
      specialized functions. The expression diversification of the duplicated genes
      suggested it might be a universal feature of the long-term evolution of cotton.
      CONCLUSIONS: Overview of cotton bHLH proteins indicated a conserved and divergent
      evolution from diploids to allotetraploid. Our results provided an excellent
      example for studying the long-term evolution of polyploidy.

PMID- 29471804
TI  - Genetic mapping and comparative genomics to inform restoration enhancement and
      culture of southern flounder, Paralichthys lethostigma.
AB  - BACKGROUND: Southern flounder, Paralichthys lethostigma, historically support a
      substantial fishery along the Atlantic and Gulf coasts of the southern United
      States. Low year-class strengths over the past few years in the western Gulf of
      Mexico have raised concern that spawning stocks may be overfished. Current
      management of the resource includes releasing hatchery-raised juveniles to
      restock bays and estuaries; additionally, there is a growing interest in the
      potential for commercial aquaculture of the species. Currently, genomic resources
      for southern flounder do not exist. Here, we used two hatchery-reared families
      and double-digest, restriction-site-associated DNA (ddRAD) sequencing to create a
      reduced-representation genomic library consisting of several thousand single
      nucleotide polymorphisms (SNPs) located throughout the genome. RESULTS: The
      relative position of each SNP-containing locus was determined to create a high
      density genetic map spanning the 24 linkage groups of the southern flounder
      genome. The consensus map was used to identify regions of shared synteny between
      southern flounder and seven other fish species for which genome assemblies are
      available. Finally, syntenic blocks were used to localize genes identified from
      transcripts in European flounder as potentially being involved in
      ecotoxicological and osmoregulatory responses, as well as QTLs associated with
      growth and disease resistance in Japanese flounder, on the southern flounder
      linkage map. CONCLUSIONS: The information provided by the linkage map will enrich
      restoration efforts by providing a foundation for interpreting spatial genetic
      variation within the species, ultimately furthering an understanding of the
      adaptive potential and resilience of southern flounder to future changes in local
      environmental conditions. Further, the map will facilitate the use of genetic
      markers to enhance restoration and commercial aquaculture.

PMID- 29471805
TI  - Single nucleotide polymorphisms in native South American Atlantic coast
      populations of smooth shelled mussels: hybridization with invasive European
      Mytilus galloprovincialis.
AB  - BACKGROUND: Throughout the world, harvesting of mussels Mytilus spp. is based on
      the exploitation of natural populations and aquaculture. Aquaculture activities
      include transfers of spat and live adult mussels between various geographic
      locations, which may result in large-scale changes in the world distribution of
      Mytilus taxa. Mytilus taxa are morphologically similar and difficult to
      distinguish. In spite of much research on taxonomy, evolution and geographic
      distribution, the native Mytilus taxa of the Southern Hemisphere are poorly
      understood. Recently, single nucleotide polymorphisms (SNPs) have been used to
      clarify the taxonomic status of populations of smooth shelled mussels from the
      Pacific coast of South America. In this paper, we used a set of SNPs to
      characterize, for the first time, populations of smooth shelled mussels Mytilus
      from the Atlantic coast of South America. RESULTS: Mytilus spp. samples were
      collected from eastern South America. Six reference samples from the Northern
      Hemisphere were used: Mytilus edulis from USA and Northern Ireland, Mytilus
      trossulus from Canada, and Mytilus galloprovincialis from Spain and Italy. Two
      other reference samples from the Southern Hemisphere were included: M.
      galloprovincialis from New Zealand and Mytilus chilensis from Chile. Fifty-five
      SNPs were successfully genotyped, of which 51 were polymorphic. Population
      genetic analyses using the STRUCTURE program revealed the clustering of eight
      populations from Argentina (Mytilus platensis) and the clustering of the sample
      from Ushuaia with M. chilensis from Chile. All individuals in the Puerto Madryn
      (Argentina) sample were identified as M. platensis * M. galloprovincialis F2
      (88.89%) hybrids, except one that was classified as Mediterranean M.
      galloprovincialis. No F1 hybrids were observed. CONCLUSIONS: We demonstrate that
      M. platensis (or Mytilus edulis platensis) and M. chilensis are distinct native
      taxa in South America, which indicates that the evolutionary histories of Mytilus
      taxa along the Atlantic and Pacific coasts differ. M. platensis is endangered by
      hybridization with M. galloprovincialis that was introduced from Europe into the
      Puerto Madryn area in Argentina, presumably by accidental introduction via ship
      traffic. We confirm the occurrence of a native M. chilensis population in
      southern Argentina on the coast of Patagonia.

PMID- 29471806
TI  - Variation of polypharmacy in older primary care attenders occurs at prescriber
      level.
AB  - BACKGROUND: Polypharmacy is particularly important in older persons as they are
      more likely to experience adverse events compared to the rest of the population.
      Despite the relevance, there is a lack of studies on the possible association of
      patient, prescriber and practice characteristics with polypharmacy. Thus, the aim
      of this study was to determine the rate of polypharmacy among older persons
      attending public and private primary care clinics, and its association with
      patient, prescriber and practice characteristics. METHODS: We used data from The
      National Medical Care Survey (NMCS), a national cross-sectional survey of
      patients' visits to primary care clinics in Malaysia. A weighted total of 22,832
      encounters of patients aged >=65 years were analysed. Polypharmacy was defined as
      concomitant use of five medications and above. Multilevel logistic regression was
      performed to examine the association of polypharmacy with patient, prescriber and
      practice characteristics. RESULTS: A total of 20.3% of the older primary care
      attenders experienced polypharmacy (26.7%% in public and 11.0% in private
      practice). The adjusted odds ratio (OR) of polypharmacy were 6.37 times greater
      in public practices. Polypharmacy was associated with patients of female gender
      (OR 1.49), primary education level (OR 1.61) and multimorbidity (OR 14.21). The
      variation in rate of polypharmacy was mainly found at prescriber level.
      CONCLUSION: Polypharmacy is common among older persons visiting primary care
      practices. Given the possible adverse outcomes, interventions to reduce the
      burden of polypharmacy are best to be directed at individual prescribers.

PMID- 29471807
TI  - The treatment of malignant glaucoma in nanophthalmos: a case report.
AB  - BACKGROUND: The management of eyes with nanophthalmos is a dilemma for
      ophthalmologists due to various complications, especial the eye with malignant
      glaucoma. We report a case of effective treatment for malignant glaucoma in
      nanophthalmos. CASE PRESENTATION: An 82-year-old man was performed
      phacoemulsification in the right eye with normal ocular pressure and
      nanophthalmos. The surgery was uneventful: an intraocular lens (IOL) was placed
      and centered in the capsular bag. 2 months later, the patient presented with
      malignant glaucoma, and the intraocular pressure fluctuated between 18.6 mmHg and
      30.8 mmHg with antiglaucoma medications. The patient did not respond to surgical
      peripheral iridotomy and goniosynechialysis. Then a single treatment with laser
      peripheral lens posterior capsulotomy and vitreous anterior membranectomy was
      performed. The intraocular pressure normalized, and the anterior chamber deepened
      within 24 h. The patient's condition remained stable for 9 months with no further
      treatment, and his Snellen corrected distance visual acuity was 20/50. The left
      eye of this patient was treated by combined surgery including
      phacoemulsification, IOL implantation, anterior vitrectomy, surgical peripheral
      iridotomy (PI), and goniosynechialysis. No intraoperative or postoperative
      complications were observed. CONCLUSIONS: This case suggests that it is essential
      to choose a suitable treatment for nanophthalmos patients to deal with malignant
      glaucoma and to reduce the incidence of malignant glaucoma.

PMID- 29471808
TI  - Whole genome duplications have provided teleosts with many roads to peptide
      loaded MHC class I molecules.
AB  - BACKGROUND: In sharks, chickens, rats, frogs, medaka and zebrafish there is
      haplotypic variation in MHC class I and closely linked genes involved in antigen
      processing, peptide translocation and peptide loading. At least in chicken, such
      MHCIa haplotypes of MHCIa, TAP2 and Tapasin are shown to influence the repertoire
      of pathogen epitopes being presented to CD8+ T-cells with subsequent effect on
      cell-mediated immune responses. RESULTS: Examining MHCI haplotype variation in
      Atlantic salmon using transcriptome and genome resources we found little evidence
      for polymorphism in antigen processing genes closely linked to the classical
      MHCIa genes. Looking at other genes involved in MHCI assembly and antigen
      processing we found retention of functional gene duplicates originating from the
      second vertebrate genome duplication event providing cyprinids, salmonids, and
      neoteleosts with the potential of several different peptide-loading complexes.
      One of these gene duplications has also been retained in the tetrapod lineage
      with orthologs in frogs, birds and opossum. CONCLUSION: We postulate that the
      unique salmonid whole genome duplication (SGD) is responsible for eliminating
      haplotypic content in the paralog MHCIa regions possibly due to frequent
      recombination and reorganization events at early stages after the SGD. In return,
      multiple rounds of whole genome duplications has provided Atlantic salmon, other
      teleosts and even lower vertebrates with alternative peptide loading complexes.
      How this affects antigen presentation remains to be established.

PMID- 29471809
TI  - Body mass index and lung cancer risk: a pooled analysis based on nested case
      control studies from four cohort studies.
AB  - BACKGROUND: Obesity has been proposed as a potential protective factor against
      lung cancer. We examined the association between BMI and lung cancer risk in a
      pooled analysis based on nested case-control studies from four cohort studies.
      METHODS: A case-control study was nested within four cohorts in USA, Europe,
      China and Singapore that included 4172 cases and 8471 control subjects. BMI at
      baseline was calculated as weight in kilograms divided by height in meters
      squared (kg/m2), and classified into 4 categories: underweight (BMI < 18.5),
      normal weight (18.5 <= BMI < 25), overweight (25 <= BMI < 30) and obese (>=30).
      Odds ratios (ORs) and 95% confidence intervals (CIs) for BMI-lung cancer
      associations were estimated using unconditional logistic regression, adjusting
      for potential confounders. RESULTS: Considering all participants, and using
      normal weight as the reference group, a decreased risk of lung cancer was
      observed for those who were overweight (OR 0.77, 95% CI: 0.68-0.86) and obese (OR
      0.69, 95% CI: 0.59-0.82). In the stratified analysis by smoking status, the
      decreased risk for lung cancer was observed among current, former and never
      smokers (P for interaction 0.002). The adjusted ORs for overweight and obese
      groups were 0.79 (95% CI: 0.68-0.92) and 0.75 (95% CI: 0.60-0.93) for current
      smokers, 0.70 (95% CI: 0.53-0.93) and 0.55 (95% CI: 0.37-0.80) for former
      smokers, 0.77 (95% CI: 0.59-0.99), and 0.71 (95% CI: 0.44-1.14) for never
      smokers, respectively. While no statistically significant association was
      observed for underweight subjects who were current smokers (OR 1.24, 95% CI: 0.98
      1.58), former smokers (OR 0.27, 95% CI: 0.12-0.61) and never smokers (OR 0.83,
      95% CI: 0.5.-1.28). CONCLUSION: The results of this study provide additional
      evidence that obesity is associated with a decreased risk of lung cancer. Further
      biological studies are needed to address this association.

PMID- 29471810
TI  - Expression and function of microRNA-9 in the mid-hindbrain area of embryonic
      chick.
AB  - BACKGROUND: MiR-9 is a small non-coding RNA that is highly conserved between
      species and primarily expressed in the central nervous system (CNS). It is known
      to influence proliferation and neuronal differentiation in the brain and spinal
      cord of different vertebrates. Different studies have pointed to regional and
      species-specific differences in the response of neural progenitors to miR-9.
      METHODS: In ovo and ex ovo electroporation was used to overexpress or reduce miR
      9 followed by mRNA in situ hybridisation and immunofluorescent stainings to
      evaluate miR- expression and the effect of changed miR-9 expression. RESULTS: We
      have investigated the expression and function of miR-9 during early development
      of the mid-hindbrain region (MH) in chick. Our analysis reveals a closer
      relationship of chick miR-9 to mammalian miR-9 than to fish and a dynamic
      expression pattern in the chick neural tube. Early in development, miR-9 is
      diffusely expressed in the entire brain, bar the forebrain, and it becomes more
      restricted to specific areas of the CNS at later stages. MiR-9 overexpression at
      HH9-10 results in a reduction of FGF8 expression and premature neuronal
      differentiation in the mid-hindbrain boundary (MHB). Within the midbrain miR-9
      does not cause premature neuronal differentiation it rather reduces proliferation
      in the midbrain. CONCLUSION: Our findings indicate that miR-9 has regional
      specific effects in the developing mid-hindbrain region with a divergence of
      response of regional progenitors.

PMID- 29471811
TI  - Ethnic differences in infectious burden and the association with metabolic risk
      factors for cardiovascular disease: a cross-sectional analysis.
AB  - BACKGROUND: The burden of metabolic risk factors for cardiovascular disease
      (CVD), such as type 2 diabetes, elevated cholesterol and hypertension, is
      unequally distributed across ethnic groups. Recent findings suggest an
      association of infectious burden (IB) and metabolic risk factors, but data from
      ethnic groups are scarce. Therefore, we investigated ethnic differences in IB and
      its association with metabolic risk factors. METHODS: We included 440 Dutch, 320
      Turkish and 272 Moroccan participants, 18-70 years, of the 2004 general health
      survey in Amsterdam, the Netherlands. IB was defined by seropositivity to the sum
      of 6 infections: Herpes Simplex Virus 1 and 2; Hepatitis A, B and C; and
      Helicobacter pylori. Associations between IB categories 4-6 (high), 3
      (intermediate) and 0-2 (low) infections and metabolic risk factors were assessed
      by logistic regression. Finally, we determined the contribution of IB to the
      association between ethnicity and the metabolic risk factors by comparing
      adjusted logistic regression models with and without IB categories. RESULTS: A
      high IB was more frequently observed among the Turkish and Moroccans than among
      the Dutch. After adjustment for age, sex, ethnicity, educational level, physical
      activity and body mass index, high IB was associated with type 2 diabetes (odds
      ratio high vs low IB (OR) =2.14, 95%-confidence interval (CI) 1.05-4.36). The
      association was weaker and not statistically significant, for elevated
      cholesterol (OR = 1.39, 95%-CI 0.82-2.34) and hypertension (OR = 1.49, 95%-CI
      0.88-2.51). IB attenuated ethnic differences particularly for type 2 diabetes.
      CONCLUSIONS: Our study showed that Turkish and Moroccan adults in Amsterdam have
      a higher IB than Dutch adults, which was associated with the differences in type
      2 diabetes. Due to the cross-sectional nature of the study, we cannot draw a
      conclusions with regards to the time-sequence of cause and effect. Nevertheless,
      the findings ask for further research into the nature of association of IB with
      metabolic risk factors in a longitudinal setting.

PMID- 29471812
TI  - Effect of weight loss on circulating fatty acid profiles in overweight subjects
      with high visceral fat area: a 12-week randomized controlled trial.
AB  - BACKGROUND: Significant associations between visceral fat and alterations in
      plasma fatty acids have been identified in overweight individuals. However, there
      are scant data regarding the relationships of the visceral fat area (VFA) with
      the plasma fatty acid profiles and desaturase activities following weight loss.
      We investigated the effect of weight loss with mild calorie restriction on the
      circulating fatty acid profiles and desaturase activities in nondiabetic
      overweight subjects with high VFA. METHODS: Eighty overweight subjects with high
      VFA (L4 VFA >=100 cm2) were randomized into the 12-week mild-calorie-restriction
      (300 kcal/day) or control groups. RESULTS: Comparison of the percent of body
      weight changes between groups revealed that the weight-loss group had greater
      reductions in body weight. The VFA decreased by 17.7 cm2 from baseline in the
      weight-loss group (P < 0.001). At follow-up, the weight-loss group showed greater
      reductions in serum triglycerides, insulin, and HOMA-IR than the control group.
      Significantly greater reductions in total saturated fatty acids, palmitic acid,
      stearic acid, total monounsaturated fatty acids, palmitoleic acid, oleic acid,
      eicosadienoic acid, and dihomo-gamma-linolenic acid levels were detected in the
      weight-loss group compared with the control group after adjusting for baseline
      values. Following weight loss, C16 Delta9-desaturase activity was significantly
      decreased and Delta5-desaturase activity was significantly increased, and the
      changes were greater in the weight-loss group than in the control group.
      CONCLUSIONS: The results suggest that mild weight loss improves abdominal
      obesity, overall fatty acid profiles, and desaturase activities; therefore, mild
      calorie restriction has potential health benefits related to obesity-related
      diseases in overweight subjects with high VFA. TRIAL REGISTRATION: NCT02992639.
      Retrospectively registered 11 December 2016.

PMID- 29471813
TI  - Rural-urban and racial-ethnic differences in awareness of direct-to-consumer
      genetic testing.
AB  - BACKGROUND: Access to direct-to-consumer genetic testing services has increased
      in recent years. However, disparities in knowledge and awareness of these
      services are not well documented. We examined awareness of genetic testing
      services by rural/urban and racial/ethnic status. METHODS: Analyses were
      conducted using pooled cross-sectional data from 4 waves (2011-2014) of the
      Health Information National Trends Survey (HINTS). Descriptive statistics
      compared sample characteristics and information sources by rural/urban residence.
      Logistic regression was used to examine the relationship between geography,
      racial/ethnic status, and awareness of genetic testing, controlling for
      sociodemographic characteristics. RESULTS: Of 13,749 respondents, 16.7% resided
      in rural areas, 13.8% were Hispanic, and 10.1% were non-Hispanic black. Rural
      residents were less likely than urban residents to report awareness of genetic
      testing (OR = 0.74, 95% CI = 0.63-0.87). Compared with non-Hispanic whites,
      racial/ethnic minorities were less likely to be aware of genetic testing:
      Hispanic (OR = 0.68, 95% CI = 0.56-0.82); and non-Hispanic black (OR = 0.74, 95%
      CI = 0.61-0.90). CONCLUSIONS: Rural-urban and racial-ethnic differences exist in
      awareness of direct-to-consumer genetic testing. These differences may translate
      into disparities in the uptake of genetic testing, health behavior change, and
      disease prevention through precision and personalized medicine.

PMID- 29471814
TI  - Moral dilemmas and conflicts concerning patients in a vegetative
      state/unresponsive wakefulness syndrome: shared or non-shared decision making? A
      qualitative study of the professional perspective in two moral case
      deliberations.
AB  - BACKGROUND: Patients in a vegetative state/ unresponsive wakefulness syndrome
      (VS/UWS) pose ethical dilemmas to those involved. Many conflicts occur between
      professionals and families of these patients. In the Netherlands physicians are
      supposed to withdraw life sustaining treatment once recovery is not to be
      expected. Yet these patients have shown to survive sometimes for decades. The
      role of the families is thought to be important. The aim of this study was to
      make an inventory of the professional perspective on conflicts in long-term care
      of patients in VS/UWS. METHODS: A qualitative study of transcripts on 2 Moral
      Deliberations (MD's) in 2 cases of patients in VS/UWS in long-term care
      facilities. RESULTS: Six themes emerged: 1) Vision on VS/UWS; 2) Treatment and
      care plan; 3) Impact on relationships; 4) Feelings/attitude; 5) Communication; 6)
      Organizational aspects. These themes are related to professionals and to what
      families had expressed to the professionals. We found conflicts as well as
      contradictory feelings and thoughts to be a general feature in 4 of these themes,
      both in professionals and families. Conflicts were found in several actors:
      within families concerning all 6 themes, in nurse teams concerning the theme
      treatment and care plan, and between physicians concerning all 6 themes.
      CONCLUSIONS: Different visions, different expectations and hope on recovery,
      deviating goals and contradictory feelings/thoughts in families and professionals
      can lead to conflicts over a patient with VS/UWS. Key factors to prevent or solve
      such conflicts are a carefully established diagnosis, clarity upon visions,
      uniformity in treatment goals and plans, an open and empathic communication,
      expertise and understanding the importance of contradictory feelings/thoughts.
      Management should bridge conflicts and support their staff, by developing
      expertise, by creating stability and by facilitating medical ethical discourses.
      Shared compassion for the patient might be a key to gain trust and bridge the
      differences from non-shared to shared decision making.

PMID- 29471815
TI  - Glucocorticosteroids and ciclosporin do not significantly impact canine cutaneous
      microbiota.
AB  - BACKGROUND: As prednisone and ciclosporin can have immunosuppressive effects and
      have been considered potential predisposing factors for skin infections, we
      investigated the impact of these drugs on the diversity of the cutaneous
      microbiota, the abundance of Malassezia and infection with Papillomaviruses.
      RESULTS: Six atopic, asymptomatic Maltese-beagle dogs were treated with
      ciclosporin for one month and then with prednisone for another month, with a one
      month wash-out between treatments. The dogs were sampled on the abdomen and pinna
      before and after each treatment using a swab. Samples for Papillomavirus
      detection were obtained with cytobrush sticks. The bacterial microbiota was
      characterized using 16S amplicon high-throughput sequencing. Malassezia
      populations were quantified with nested real-time PCR targeting the ribosomal
      internal transcribed spacer 1. The diversity and composition of cutaneous
      microbiota was not impacted in a detectable manner by any of the treatments. As
      observed for the bacterial microbiota, Malassezia populations were not affected
      by treatment. Three dogs were positive for Papillomavirus at more than one
      timepoint, but an association with treatment was not apparent. CONCLUSIONS:
      Ciclosporin and prednisone at doses used for the treatment of atopic dermatitis
      do not impact the canine cutaneous microbiota in a detectable manner.

PMID- 29471817
TI  - Health care quality measures for children and adolescents in Foster Care:
      feasibility testing in electronic records.
AB  - BACKGROUND: Preventive quality measures for the foster care population are
      largely untested. The objective of the study is to identify healthcare quality
      measures for young children and adolescents in foster care and to test whether
      the data required to calculate these measures can be feasibly extracted and
      interpreted within an electronic health records or within the Statewide Automated
      Child Welfare Information System. METHODS: The AAP Recommendations for Preventive
      Pediatric Health Care served as the guideline for determining quality measures.
      Quality measures related to well child visits, developmental screenings,
      immunizations, trauma-related care, BMI measurements, sexually transmitted
      infections and depression were defined. Retrospective chart reviews were
      performed on a cohort of children in foster care from a single large pediatric
      institution and related county. Data available in the Ohio Statewide Automated
      Child Welfare Information System was compared to the same population studied in
      the electronic health record review. Quality measures were calculated as observed
      (received) to expected (recommended) ratios (O/E ratios) to describe the actual
      quantity of recommended health care that was received by individual children.
      RESULTS: Electronic health records and the Statewide Automated Child Welfare
      Information System data frequently lacked important information on foster care
      youth essential for calculating the measures. Although electronic health records
      were rich in encounter specific clinical data, they often lacked custodial
      information such as the dates of entry into and exit from foster care. In
      contrast, Statewide Automated Child Welfare Information System included robust
      data on custodial arrangements, but lacked detailed medical information. Despite
      these limitations, several quality measures were devised that attempted to
      accommodate these limitations. CONCLUSIONS: In this feasibility testing, neither
      the electronic health records at a single institution nor the county level
      Statewide Automated Child Welfare Information System was able to independently
      serve as a reliable source of data for health care quality measures for foster
      care youth. However, the ability to leverage both sources by matching them at an
      individual level may provide the complement of data necessary to assess the
      quality of healthcare.

PMID- 29471816
TI  - Idiopathic pulmonary fibrosis: pathogenesis and management.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease
      characterized by the aberrant accumulation of fibrotic tissue in the lungs
      parenchyma, associated with significant morbidity and poor prognosis. This review
      will present the substantial advances achieved in the understanding of IPF
      pathogenesis and in the therapeutic options that can be offered to patients, and
      will address the issues regarding diagnosis and management that are still open.
      MAIN BODY: Over the last two decades much has been clarified about the pathogenic
      pathways underlying the development and progression of the lung scarring in IPF.
      Sustained alveolar epithelial micro-injury and activation has been recognised as
      the trigger of several biological events of disordered repair occurring in
      genetically susceptible ageing individuals. Despite multidisciplinary team
      discussion has demonstrated to increase diagnostic accuracy, patients can still
      remain unclassified when the current diagnostic criteria are strictly applied,
      requiring the identification of a Usual Interstitial Pattern either on high
      resolution computed tomography scan or lung biopsy. Outstanding achievements have
      been made in the management of these patients, as nintedanib and pirfenidone
      consistently proved to reduce the rate of progression of the fibrotic process.
      However, many uncertainties still lie in the correct use of these drugs, ranging
      from the initial choice of the drug, the appropriate timing for treatment and the
      benefit-risk ratio of a combined treatment regimen. Several novel compounds are
      being developed in the perspective of a more targeted therapeutic approach; in
      the meantime, the supportive care of these patients and their carers should be
      appropriately prioritized, and greater efforts should be made toward the prompt
      identification and management of relevant comorbidities. CONCLUSIONS: Building on
      the advances in the understanding of IPF pathobiology, the further investigation
      of the role of gene variants, epigenetic alterations and other molecular
      biomarkers reflecting disease activity and behaviour will hopefully enable
      earlier and more confident diagnosis, improve disease phenotyping and support the
      development of novel agents for personalized treatment of IPF.

PMID- 29471818
TI  - Adult Wilms tumor with inferior vena cava thrombus and distal deep vein
      thrombosis - a case report and literature review.
AB  - BACKGROUND: Adult Wilms tumor (WT, nephroblastoma) is a rare, but well-described
      renal neoplasm. Although inferior vena cava tumor thrombosis is present in up to
      10% of Wilms tumors in childhood, only few cases of this clinical manifestation
      in adults have been reported. To the best of our knowledge, this is the first
      case of adult WT infiltrating into inferior vena cava (IVC) with concomitant
      distal deep vein thrombosis. CASE PRESENTATION: A 28-year-old male patient with
      gross hematuria and right flank pain was diagnosed with right kidney tumor
      penetrating to IVC. Preoperatively, acute distal thrombosis in inferior vena cava
      and lower extremities veins occurred. Right radical nephrectomy with tumor
      thrombectomy via cavotomy was performed. In order to prevent pulmonary embolism,
      IVC was ligated below left renal vein level. Histopathological examination
      revealed a triphasic nephroblastoma without anaplastic features. Postoperatively,
      patient was diagnosed with metastatic liver disease, which was treated with two
      lines of chemotherapy followed by radiotherapy with achievement of complete
      response. CONCLUSIONS: Adult WT occurs usually in young patients, under 40 years
      of age. Neoadjuvant chemotherapy proved to be effective in children, resulting
      with tumor shrinkage and venous tumor thrombus regression. Therefore,
      percutaneous biopsy should be always considered in young patients presenting with
      renal tumor invading venous system. IVC ligation is a safe treatment option in
      the event of complete inferior vena cava occlusion due to distal thrombosis
      concomitant to tumor thrombus, provided collateral venous pathways are well
      developed.

PMID- 29471819
TI  - Dengue periodic outbreaks and epidemiological trends in Nepal.
AB  - Dengue is a global health problem and expansion of its endemics towards new
      territories in the hilly regions in Nepal is a serious concern. It appeared as a
      new disease in Nepal in 2004 from Japanese traveler with sporadic cases every
      year and massive outbreaks in 2010, 2013 and 2016. The serotype was responsible
      for outbreak in particular year was dengue virus serotype-1 (DENV-1) in 2010,
      2016; and DENV-2 in 2013. Nepal lacks basic health related infrastructure in
      rural areas and does not have a stringent health care policy. With severances of
      epidemic like dengue, a new surveillance or an upgrading of existing one are
      direly needed to better challenge the possible outbreaks. This review paper aims
      to explain the dengue trend in last one decade in Nepal and warrants concerted
      and timely public health interventions to minimize the deleterious effects of the
      disease.

PMID- 29471820
TI  - Directly mining a fungal thermostable alpha-amylase from Chinese Nong-flavor
      liquor starter.
AB  - BACKGROUND: Chinese Nong-flavor (NF) liquor is continuously and stably produced
      by solid-state fermentation technology for 1000 years, resulting in enrichment of
      special microbial community and enzymes system in its starter. Based on
      traditional culture-dependent methods, these functional enzymes are hardly
      obtained. According to our previous metatranscriptomic analysis, which identifies
      plenty of thermostable carbohydrate-active enzymes in NF liquor starter, the aim
      of this study is to provide a direct and efficient way to mine these thermostable
      enzymes. RESULTS: In present study, an alpha-amylase (NFAmy13A) gene, which
      showed the highest expression level of enzymes in starch degradation at high
      temperature stage (62  degrees C), was directly obtained by functional
      metatranscriptomics from Chinese Nong-flavor liquor starter and expressed in
      Pichia pastoris. NFAmy13A had a typical signal peptide and shared the highest
      sequence identity of 64% with alpha-amylase from Aspergillus niger. The
      recombinant enzyme of NFAmy13A showed an optimal pH at 5.0-5.5 and optimal
      temperature at 60  degrees C. NFAmy13A was activated and stabilized by Ca2+, and
      its half-lives at 60 and 70  degrees C were improved significantly from 1.5 and
      0.4 h to 16 and 0.7 h, respectively, in the presence of 10 mM CaCl2. Meanwhile,
      Hg2+, Co2+ and SDS largely inhibited its activity. NFAmy13A showed the maximum
      activity on amylopectin, followed by various starches, amylose, glycogen, and
      pullulan, and its specificity activity on amylopectin was 200.4 U/mg. Moreover,
      this alpha-amylase efficiently hydrolyzed starches (from corn, wheat, and potato)
      at high concentrations up to 15 mg/ml. CONCLUSIONS: This study provides a direct
      way to mine active enzymes from man-made environment of NF liquor starter, by
      which a fungal thermostable alpha-amylase (NFAmy13A) is successfully obtained.
      The good characteristics of NFAmy13A in degrading starch at high temperature are
      consistent with its pivotal role in solid-state fermentation of NF liquor
      brewing. This work would stimulate mining more enzymes from NF liquor starter and
      studying their potentially synergistic roles in NF liquor brewing, thus paving
      the way toward the optimization of liquor production and improvement of liquor
      quality in future.

PMID- 29471821
TI  - Decision-making at the limit of viability: differing perceptions and opinions
      between neonatal physicians and nurses.
AB  - BACKGROUND: In the last 20 years, the chances for intact survival for extremely
      preterm infants have increased in high income countries. Decisions about
      withholding or withdrawing intensive care remain a major challenge in infants
      born at the limits of viability. Shared decision-making regarding these fragile
      infants between health care professionals and parents has become the preferred
      model today. However, there is an ongoing ethical debate on how decisions
      regarding life-sustaining treatment should be reached and who should have the
      final word when health care professionals and parents do not agree. We designed a
      survey among neonatologists and neonatal nurses to analyze practices,
      difficulties and parental involvement in end-of-life decisions for extremely
      preterm infants. METHODS: All 552 physicians and nurses with at least 12 months
      work experience in level III neonatal intensive care units (NICU) in Switzerland
      were invited to participate in an online survey with 50 questions. Differences
      between neonatologists and NICU nurses and between language regions were
      explored. RESULTS: Ninety six of 121 (79%) physicians and 302 of 431(70%) nurses
      completed the online questionnaire. The following difficulties with end-of-life
      decision-making were reported more frequently by nurses than physicians:
      insufficient time for decision-making, legal constraints and lack of consistent
      unit policies. Nurses also mentioned a lack of solidarity in our society and
      shortage of services for disabled more often than physicians. In the context of
      limiting intensive care in selected circumstances, nurses considered withholding
      tube feedings and respiratory support less acceptable than physicians. Nurses
      were more reluctant to give parents full authority to decide on the course of
      action for their infant. In contrast to professional category (nurse or
      physician), language region, professional experience and religion had little
      influence if any on the answers given. CONCLUSIONS: Physicians and nurses differ
      in many aspects of how and by whom end-of-life decisions should be made in
      extremely preterm infants. The divergencies between nurses and physicians may be
      due to differences in ethics education, varying focus in patient care and direct
      exposure to the patients. Acknowledging these differences is important to avoid
      potential conflicts within the neonatal team but also with parents in the process
      of end-of-life decision-making in preterm infants born at the limits of
      viability.

PMID- 29471822
TI  - Direct whole-genome sequencing of Plasmodium falciparum specimens from dried
      erythrocyte spots.
AB  - BACKGROUND: Plasmodium falciparum malaria remains a major health burden and
      genomic research represents one of the necessary approaches for continued
      progress towards malaria control and elimination. Sample acquisition for this
      purpose is troublesome, with the majority of malaria-infected individuals living
      in rural areas, away from main infrastructure and the electrical grid. The aim of
      this study was to describe a low-tech procedure to sample P. falciparum specimens
      for direct whole genome sequencing (WGS), without use of electricity and cold
      chain. METHODS: Venous blood samples were collected from malaria patients in
      Bandim, Guinea-Bissau and leukocyte-depleted using Plasmodipur filters, the
      enriched parasite sample was spotted on Whatman paper and dried. The samples were
      stored at ambient temperatures and subsequently used for DNA-extraction. Ratios
      of parasite:human content of the extracted DNA was assessed by qPCR, and five
      samples with varying parasitaemia, were sequenced. Sequencing data were used to
      analyse the sample content, as well as sample coverage and depth as compared to
      the 3d7 reference genome. RESULTS: qPCR revealed that 73% of the 199 samples were
      applicable for WGS, as defined by a minimum ratio of parasite:human DNA of 2:1.
      WGS revealed an even distribution of sequence data across the 3d7 reference
      genome, regardless of parasitaemia. The acquired read depths varied from 16 to
      99*, and coverage varied from 87.5 to 98.9% of the 3d7 reference genome. SNP
      analysis of six genes, for which amplicon sequencing has been performed
      previously, confirmed the reliability of the WGS-data. CONCLUSION: This study
      describes a simple filter paper based protocol for sampling P. falciparum from
      malaria patients for subsequent direct WGS, enabling acquisition of samples in
      remote settings with no access to electricity.

PMID- 29471823
TI  - Unidimensional scales for fears of cancer recurrence and their psychometric
      properties: the FCR4 and FCR7.
AB  - BACKGROUND: The assessment of fear of recurrence (FCR) is crucial for
      understanding an important psychological state in patients diagnosed and treated
      for cancer. The study aim was to determine psychometric details of a seven
      question self-report scale (FCR7) and a short form (FCR4) based upon items
      already used in various extensive measures of FCR. METHODS: Two consecutive
      samples of patients (breast and colorectal) were recruited from a single
      specialist cancer centre. The survey instrument contained the FCR7 items,
      Hospital Anxiety and Depression Scale (HADS), and demographic details. Clinical
      information was obtained from patient hospital records. Statistical analyses were
      performed using classical test and item response theory approaches, to
      demonstrate unidimensional factor structure and testing key parameters. Construct
      validity was inspected through nomological and theoretical prediction. RESULTS:
      Internal consistency was demonstrated by alpha coefficients (FCR4: 0.93 and FCR7:
      0.92). Both scales (FCR7 & FCR4) were associated with the HADs subscales as
      predicted. Patients who experienced chemotherapy, minor aches/pains, thought
      avoidance of cancer and high cancer risk belief were more fearful. Detailed
      inspection of item responses profile provided some support for measurement
      properties of scales. CONCLUSION: The internal consistency, and pattern of key
      associations and discriminability indices provided positive psychometric evidence
      for these scales. The brief measures of FCR may be considered for audit,
      screening or routine use in clinical service and research investigations.

PMID- 29471824
TI  - Perceived stress, reasons for and sources of stress among medical students at
      Rabigh Medical College, King Abdulaziz University, Jeddah, Saudi Arabia.
AB  - BACKGROUND: Medical students have high levels of stress that could be due to the
      daily life stressors and the extra stress of academic burden. The present study
      investigated the perceived stress level as well as the reasons and sources of
      stress among medical students at a comparatively newly established medical
      college affiliated with King Abdulaziz University (KAU), Jeddah, Saudi Arabia
      (SA). METHODS: The present study was carried out at Rabigh Medical College (RMC),
      KAU, Jeddah, and completed in 2015. The data was collected by an anonymous self
      administered questionnaire that has three components: a list of 33 items of
      probable stressors, perceived stress scale, and demographic information and
      academics. RESULTS: The response rate in our study was 86% (152/176), the mean
      age was 20.35 +/- 1.09, 77 (51%) were from preclinical years and 75 (49%) from
      clinical years. The mean PSS score among our participants was 28.5 +/- 3.8 with a
      median of 28.0 (IQR 26.0-31.0) and 59.2% of participants were stressed. The mean
      PSS score 30.6 +/- 4.4 for students with sibling > 5 was significantly higher as
      compared to the mean PSS score (27.9 +/- 3.3) for students with sibling <=5.
      Similarly, the mean PSS score (32.0 +/- 3.4) of students with often/always
      occurrence of psychosocial stressors was higher as compared to the mean PSS score
      (28.3 +/- 3.7) of those students with less than a frequent occurrence of
      stressors. Moreover, those students that were more stressed had lower marks in
      the last exam (< 80%) as compared to students with less stress who had higher
      marks (>=80%) (P < .05). Performance in practicals, examinations frequency,
      disappointment with the class lectures, lack of personal interest in medicine,
      lengthy academic curriculum/syllabus, worries about the future and periodic
      examinations performance were rated as severe. The logistic regression analysis
      showed that stress cases were linked with last exam marks [OR 1.26, 95% CI 0.64
      2.48], number of siblings [OR 2.27, 95% CI 0.97-5.27], and academic stressor [OR
      2.02, 95% CI 0.61-6.66] but no significant relationship was found. CONCLUSION:
      There were high-stress levels among the participants of this study, and the main
      stressors were academic-related.

PMID- 29471825
TI  - Finish line distinctness and accuracy in 7 intraoral scanners versus conventional
      impression: an in vitro descriptive comparison.
AB  - BACKGROUND: Several studies have evaluated accuracy of intraoral scanners (IOS),
      but data is lacking regarding variations between IOS systems in the depiction of
      the critical finish line and the finish line accuracy. The aim of this study was
      to analyze the level of finish line distinctness (FLD), and finish line accuracy
      (FLA), in 7 intraoral scanners (IOS) and one conventional impression (IMPR).
      Furthermore, to assess parameters of resolution, tessellation, topography, and
      color. METHODS: A dental model with a crown preparation including supra and
      subgingival finish line was reference-scanned with an industrial scanner (ATOS),
      and scanned with seven IOS: 3M, CS3500 and CS3600, DWIO, Omnicam, Planscan and
      Trios. An IMPR was taken and poured, and the model was scanned with a laboratory
      scanner. The ATOS scan was cropped at finish line and best-fit aligned for 3D
      Compare Analysis (Geomagic). Accuracy was visualized, and descriptive analysis
      was performed. RESULTS: All IOS, except Planscan, had comparable overall
      accuracy, however, FLD and FLA varied substantially. Trios presented the highest
      FLD, and with CS3600, the highest FLA. 3M, and DWIO had low overall FLD and low
      FLA in subgingival areas, whilst Planscan had overall low FLD and FLA, as well as
      lower general accuracy. IMPR presented high FLD, except in subgingival areas, and
      high FLA. Trios had the highest resolution by factor 1.6 to 3.1 among IOS,
      followed by IMPR, DWIO, Omnicam, CS3500, 3M, CS3600 and Planscan. Tessellation
      was found to be non-uniform except in 3M and DWIO. Topographic variation was
      found for 3M and Trios, with deviations below +/- 25 MUm for Trios. Inclusion of
      color enhanced the identification of the finish line in Trios, Omnicam and
      CS3600, but not in Planscan. CONCLUSIONS: There were sizeable variations between
      IOS with both higher and lower FLD and FLA than IMPR. High FLD was more related
      to high localized finish line resolution and non-uniform tessellation, than to
      high overall resolution. Topography variations were low. Color improved finish
      line identification in some IOS. It is imperative that clinicians critically
      evaluate the digital impression, being aware of varying technical limitations
      among IOS, in particular when challenging subgingival conditions apply.

PMID- 29471826
TI  - The family talk intervention in palliative care: a study protocol.
AB  - BACKGROUND: In palliative care contexts, support programs for families with a
      severely ill parent and minor children are few, and even fewer have been
      evaluated scientifically. The aims of this study are to examine feasibility and
      potential effects of a modified version of the Family Talk Intervention (FTI) in
      palliative care. METHODS: This ongoing family-centered intervention has a quasi
      experimental design comparing one intervention and one comparison group. The
      intervention includes severely ill parents who have minor children (aged 6-19
      yrs) and are receiving advanced homecare in Stockholm, Sweden between March 2017
      and March 2018. The main goal of the FTI is to support family communication
      through psycho-education and narrative theory. The modified FTI consists of six
      meetings with family members, and is held by two interventionists. Each family
      sets up needs-based goals for the intervention. For evaluation purposes, data are
      collected by questionnaire before the intervention, within two months after
      baseline, and one year after baseline. Interviews will be conducted within two
      months after FTI is completed. Notes taken by one of the interventionists during
      the family meetings will also be used. Questionnaire data analysis will focus on
      patterns over time using descriptive statistics. For interview data and notes,
      content analysis will be used. DISCUSSION: This study will add knowledge about
      palliative care for parents who have minor children. It will contribute by
      testing use of FTI in palliative care, and point out directions for future
      evaluations of FTI in palliative care settings. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier NCT03119545 , retrospectively registered in April
      18, 2017.

PMID- 29471828
TI  - A Delphi study and ranking exercise to support commissioning services: future
      delivery of Thrombectomy services in England.
AB  - BACKGROUND: Intra-arterial thrombectomy is the gold standard treatment for large
      artery occlusive stroke. However, the evidence of its benefits is almost entirely
      based on trials delivered by experienced neurointerventionists working in
      established teams in neuroscience centres. Those responsible for the design and
      prospective reconfiguration of services need access to a comprehensive and
      complementary array of information on which to base their decisions. This will
      help to ensure the demonstrated effects from trials may be realised in practice
      and account for regional/local variations in resources and skill-sets. One
      approach to elucidate the implementation preferences and considerations of key
      experts is a Delphi survey. In order to support commissioning decisions, we aimed
      using an electronic Delphi survey to establish consensus on the options for
      future organisation of thrombectomy services among physicians with clinical
      experience in managing large artery occlusive stroke. METHODS: A Delphi survey
      was developed with 12 options for future organisation of thrombectomy services in
      England. A purposive sampling strategy established an expert panel of stroke
      physicians from the British Association of Stroke Physicians (BASP) Clinical
      Standards and/or Executive Membership that deliver 24/7 intravenous thrombolysis.
      Options with aggregate scores falling within the lowest quartile were removed
      from the subsequent Delphi round. Options reaching consensus following the two
      Delphi rounds were then ranked in a final exercise by both the wider BASP
      membership and the British Society of Neuroradiologists (BSNR). RESULTS: Eleven
      stroke physicians from BASP completed the initial two Delphi rounds. Three
      options achieved consensus, with subsequently wider BASP (97%, n = 43) and BSNR
      members (86%, n = 21) assigning the highest approval rankings in the final
      exercise for transferring large artery occlusive stroke patients to nearest
      neuroscience centre for thrombectomy based on local CT/CT Angiography.
      CONCLUSIONS: The initial Delphi rounds ensured optimal reduction of options by an
      expert panel of stroke physicians, while subsequent ranking exercises allowed
      remaining options to be ranked by a wider group of experts within stroke to reach
      consensus. The preferred implementation option for thrombectomy is investigating
      suspected acute stroke patients by CT/CT Angiography and secondary transfer of
      large artery occlusive stroke patients to the nearest neuroscience (thrombectomy)
      centre.

PMID- 29471829
TI  - Transcriptional profiles of different states of cancer stem cells in triple
      negative breast cancer.
AB  - Breast cancer stem cells (BCSCs) are thought to be responsible for tumor
      initiation, metastasis and relapse. Our group and others have described markers
      useful in isolating BCSCs just as aldehyde dehydrogenase positive (ALDH+) or CD24
      CD44+. In fact, cells which simultaneously express both sets of markers have the
      highest tumor initiating capacity. Although the transcriptomic profile of cells
      expressing each BCSC marker alone has been reported, the profile of the most
      tumorigenic population expressing both sets of markers has not. Here we used the
      biomarker combination of ALDH and CD24/CD44 to sort four populations isolated
      from triple-negative breast cancer (TNBC) patient-derived xenografts, and
      performed whole-transcriptome sequencing on each population. We systematically
      compared the profiles of the three states of BCSCs (ALDH+CD24-CD44+, ALDH+non
      CD24-CD44+ and ALDH-CD24-CD44+) to that of the differentiated tumor cells (ALDH
      non-CD24-CD44+). For the first time, we compared the ALDH+CD24-CD44+ BCSCs with
      the other two BCSC populations. In ALDH+CD24-CD44+ BCSCs, we identified P4HA2,
      PTGR1 and RAB40B as potential prognostic markers, which were virtually related to
      the status of BCSCs and tumor growth in TNBC cells.

PMID- 29471827
TI  - Nuclear functions of mammalian MicroRNAs in gene regulation, immunity and cancer.
AB  - MicroRNAs (miRNAs) are endogenous non-coding RNAs that contain approximately 22
      nucleotides. They serve as key regulators in various biological processes and
      their dysregulation is implicated in many diseases including cancer and
      autoimmune disorders. It has been well established that the maturation of miRNAs
      occurs in the cytoplasm and miRNAs exert post-transcriptional gene silencing
      (PTGS) via RNA-induced silencing complex (RISC) pathway in the cytoplasm.
      However, numerous studies reaffirm the existence of mature miRNA in the nucleus,
      and nucleus-cytoplasm transport mechanism has also been illustrated. Moreover,
      active regulatory functions of nuclear miRNAs were found including PTGS,
      transcriptional gene silencing (TGS), and transcriptional gene activation (TGA),
      in which miRNAs bind nascent RNA transcripts, gene promoter regions or enhancer
      regions and exert further effects via epigenetic pathways. Based on existing
      interaction rules, some miRNA binding sites prediction software tools are
      developed, which are evaluated in this article. In addition, we attempt to
      explore and review the nuclear functions of miRNA in immunity, tumorigenesis and
      invasiveness of tumor. As a non-canonical aspect of miRNA action, nuclear miRNAs
      supplement miRNA regulatory networks and could be applied in miRNA based
      therapies.

PMID- 29471830
TI  - Beyond coverage: improving the quality of antenatal care delivery through
      integrated mentorship and quality improvement at health centers in rural Rwanda.
AB  - BACKGROUND: Inadequate antenatal care (ANC) can lead to missed diagnosis of
      danger signs or delayed referral to emergency obstetrical care, contributing to
      maternal mortality. In developing countries, ANC quality is often limited by
      skill and knowledge gaps of the health workforce. In 2011, the Mentorship,
      Enhanced Supervision for Healthcare and Quality Improvement (MESH-QI) program was
      implemented to strengthen providers' ANC performance at 21 rural health centers
      in Rwanda. We evaluated the effect of MESH-QI on the completeness of danger sign
      assessments. METHODS: Completeness of danger sign assessments was measured by
      expert nurse mentors using standardized observation checklists. Checklists
      completed from October 2010 to May 2011 (n = 330) were used as baseline
      measurement and checklists completed between February and November 2012 (12-15
      months after the start of MESH-QI implementation) were used for follow-up. We
      used a mixed-effects linear regression model to assess the effect of the MESH-QI
      intervention on the danger sign assessment score, controlling for potential
      confounders and the clustering of effect at the health center level. RESULTS:
      Complete assessment of all danger signs improved from 2.1% at baseline to 84.2%
      after MESH-QI (p <  0.001). Similar improvements were found for 20 of 23 other
      essential ANC screening items. After controlling for potential confounders, the
      improvement in danger sign assessment score was significant. However, the effect
      of the MESH-QI was different by intervention district and type of observed ANC
      visit. In Southern Kayonza District, the increase in the danger sign assessment
      score was 6.28 (95% CI: 5.59, 6.98) for non-first ANC visits and 5.39 (95% CI:
      4.62, 6.15) for first ANC visits. In Kirehe District, the increase in danger sign
      assessment score was 4.20 (95% CI: 3.59, 4.80) for non-first ANC visits and 3.30
      (95% CI: 2.80, 3.81) for first ANC visits. CONCLUSION: Assessment of critical
      danger signs improved under MESH-QI, even when controlling for nurse-mentees'
      education level and previous training in focused ANC. MESH-QI offers an approach
      to enhance quality of care after traditional training and may be an approach to
      support newer providers who have not yet attended content-focused courses.

PMID- 29471831
TI  - Prediction of suboptimal cytoreductive surgery in patients with advanced ovarian
      cancer based on preoperative and intraoperative determination of the peritoneal
      carcinomatosis index.
AB  - BACKGROUND: The peritoneal carcinomatosis index (PCI) can be used to quantify the
      tumor burden in patients with advanced ovarian cancer. The aim of the present
      study was to establish a predictive model for suboptimal cytoreductive surgery
      (SCS) (residual tumor of > 1 cm) using preoperative and intraoperative
      determination of the PCI. METHODS: In total, 110 consecutive patients treated for
      advanced ovarian cancer during a 4-year period in our institution were assessed.
      Eighty of these patients were eligible for primary debulking surgery and thus
      included in the present study. All data were prospectively collected and
      retrospectively evaluated. We determined the PCI both preoperatively and
      intraoperatively and assessed postoperative complications. RESULTS: A PCI of > 20
      was the best cut-off with which to predict a risk of SCS among all three
      diagnostic techniques assessed in this study (computed tomography, laparoscopy,
      and laparotomy). Intraoperative PCI determination was associated with the lowest
      risk of false negatives for SCS when detecting a PCI of < 20. The combination of
      preoperative computed tomography and laparoscopy, when both techniques predicted
      SCS, was associated with the lowest risk of false positives for SCS when
      detecting a PCI of > 20. CONCLUSION: The combination of computed tomography and
      laparoscopy to obtain the PCI can help to determine which patients with advanced
      ovarian cancer are suitable for primary debulking surgery and which should
      undergo neoadjuvant chemotherapy.

PMID- 29471832
TI  - Accuracy and impact of spatial aids based upon satellite enumeration to improve
      indoor residual spraying spatial coverage.
AB  - BACKGROUND: Indoor residual spraying (IRS) is a key tool in the fight to control,
      eliminate and ultimately eradicate malaria. IRS protection is based on a communal
      effect such that an individual's protection primarily relies on the community
      level coverage of IRS with limited protection being provided by household-level
      coverage. To ensure a communal effect is achieved through IRS, achieving high and
      uniform community-level coverage should be the ultimate priority of an IRS
      campaign. Ensuring high community-level coverage of IRS in malaria-endemic areas
      is challenging given the lack of information available about both the location
      and number of households needing IRS in any given area. A process termed 'mSpray'
      has been developed and implemented and involves use of satellite imagery for
      enumeration for planning IRS and a mobile application to guide IRS
      implementation. This study assessed (1) the accuracy of the satellite enumeration
      and (2) how various degrees of spatial aid provided through the mSpray process
      affected community-level IRS coverage during the 2015 spray campaign in Zambia.
      METHODS: A 2-stage sampling process was applied to assess accuracy of satellite
      enumeration to determine number and location of sprayable structures. Results
      indicated an overall sensitivity of 94% for satellite enumeration compared to
      finding structures on the ground. RESULTS: After adjusting for structure size,
      roof, and wall type, households in Nchelenge District where all types of
      satellite-based spatial aids (paper-based maps plus use of the mobile mSpray
      application) were used were more likely to have received IRS than Kasama district
      where maps used were not based on satellite enumeration. The probability of a
      household being sprayed in Nchelenge district where tablet-based maps were used,
      did not differ statistically from that of a household in Samfya District, where
      detailed paper-based spatial aids based on satellite enumeration were provided.
      CONCLUSION: IRS coverage from the 2015 spray season benefited from the use of
      spatial aids based upon satellite enumeration. These spatial aids can guide
      costly IRS planning and implementation leading to attainment of higher spatial
      coverage, and likely improve disease impact.

PMID- 29471833
TI  - Plasmodium falciparum diagnostic tools in HIV-positive under-5-year-olds in two
      ART clinics in Ghana: are there missed infections?
AB  - BACKGROUND: Plasmodium falciparum, the most dominant species in sub-Saharan
      Africa, causes the most severe clinical malaria manifestations. In resource
      limited Ghana, where malaria and HIV geographically overlap, histidine-rich
      protein 2 (HRP2)-based rapid diagnostic test (RDT) is a faster, easier and
      cheaper alternative to clinical gold standard light microscopy. However,
      mutations in parasite hrp2 gene may result in missed infections, which have
      severe implications for malaria control. METHODS: The performance of a common
      HRP2-based RDT and expert light microscopy in HIV-positive and HIV-negative
      children under 5 years old was compared with PCR as laboratory gold standard.
      Finger-prick capillary blood was tested with First Response(r) Malaria Ag P.
      falciparum (HRP2). Giemsa-stained thick and thin blood films were examined with
      >= 200 high power fields and parasites counted per 200 white blood cells. Nested
      PCR species identification of P. falciparum was performed and resolved on agarose
      gel. False negatives from RDT were further tested for deleted pfhrp2/3 and
      flanking genes, using PCR. The study was performed in two anti-retroviral therapy
      clinics in Accra and Atibie. RESULTS: Out of 401 participants enrolled, 150 were
      HIV positive and 251 HIV negative. Malaria was more prevalent in children without
      HIV. Microscopy had a higher sensitivity [100% (99-100)] than RDT [83% (53.5
      100)]. Parasites with pfhrp2/3 deletions contributed to missed infections from
      RDT false negatives. CONCLUSION: Circulation of malaria parasites with pfrhp2/3
      deletions in this population played a role in missed infections with RDT. This
      ought to be addressed if further strides in malaria control are to be made.

PMID- 29471834
TI  - Widening disparities in health between educational levels and their determinants
      in later life: evidence from a nine-year cohort study.
AB  - BACKGROUND: Education has attracted more attention as a key determinant of health
      in later life. In this study, the hypothesis that widened educational disparities
      in health can be observed in later life was investigated, and the factors that
      mediated the association between education and changes in health were also
      assessed. METHODS: Using the 9-year (10-wave) longitudinal data of 20,024
      individuals (9320 men and 10,704 women) aged 50-59 years at baseline, collected
      from a nationwide population survey in Japan (2005-2014), the changes in self
      rated health, functional limitations, and psychological distress between
      educational levels were compared. Mediation analysis was further conducted to
      assess the factors that mediated the association between education and changes in
      health, with reference to six types of potential mediators (household spending,
      social participation, leisure-time physical activity, smoking, problem drinking,
      and regular health check-ups). The analyses were conducted separately for men and
      women. RESULTS: All three health variables rapidly deteriorated among lower
      educated men and women. For men, the six potential mediators mediated 55.2%,
      64.3%, and 47.3% of the associations between educational levels and changes in
      self-rated health, functional limitations, and psychological distress,
      respectively. The proportions for women were 42.0%, 49.5%, and 58.8%,
      respectively. Social participation was the primary mediator, followed by physical
      activity, regular health check-ups, and smoking. In general, no substantial or
      consistent differences were observed between men and women. CONCLUSIONS: The
      results suggested that policy measures that encourage social participation and
      promote healthy behaviors can improve educational disparities in health in later
      life.

PMID- 29471835
TI  - Dietary quality linkage to overall competence at school and emotional disturbance
      in representative Taiwanese young adolescents: dependence on gender, parental
      characteristics and personal behaviors.
AB  - BACKGROUND: Child school performance during puberty may be at increased risk
      through emotional disturbance. It is hypothesized that this may be mitigated by
      dietary quality. METHODS: In a nationally representative sample (Nutrition and
      Health Survey in Taiwan, NAHSIT), 1371 Taiwanese aged 11-16 years, overall
      competence at school, (OCS) and emotional status have been assessed by teachers
      with the SAED (Scale for Assessing Emotional Disturbance). Parents provided
      family socio-demographics and students completed a behavioral and dietary
      questionnaire (Youth Healthy Eating Index - Taiwan, YHEI-TW). Associations
      between emotional disturbance (ED), OCS and dietary quality (YHEI-TW) were
      assessed in multiple linear regression models with adjustments for covariates
      including parental characteristics, personal behaviors, body fatness and puberty.
      RESULTS: Boys or girls with ED had a less favorable OCS (p < 0.001), minimally
      dependent on YHEI-TW. On multivariable analysis there was a more positive
      association between OCS and YHEI-TW among boys (beta = 0.05, p < 0.01) and girls
      (beta = 0.07, p < 0.001). Poor dietary quality was associated with ED, especially
      in girls (beta =  - 0.06, p < 0.001). Additionally, parental characteristics,
      body fatness, and personal behaviors are associated with OCS. Puberty is
      associated with ED and may be indirectly linked to OCS. CONCLUSIONS:
      Unsatisfactory food intake is associated with the link between emotional
      disturbance and impaired school performance, as assessed by OCS, especially among
      girls. For both genders, socio-economic and behavioral factors including
      parenteral income, reading, screen viewing and smoking are modulators of this
      association. Puberty was a modifying factor in girls. Dietary quality is a
      relevant factor for health (ED) as well as education (OCS) during early
      adolescence.

PMID- 29471837
TI  - The effect of knowledge on uptake of breast cancer prevention modalities among
      women in Kyadondo County, Uganda.
AB  - BACKGROUND: Breast cancer, the third most frequent cancer of women is preventable
      through knowledge on breast self-examination. Of the 44% of women diagnosed with
      breast cancer at the Uganda Cancer Institute, only 22% go for check-up in less
      than three months. This study explored the effect of breast cancer knowledge on
      the uptake of breast cancer prevention modalities among women in Kyadondo County,
      Uganda. METHODS: A household survey of women in Kyadondo County was conducted
      during June, 2014 to August, 2015. This involved studying in-depth using a
      questionnaire the level of breast cancer knowledge of the respondents. Data was
      analyzed using logistic regression model. Chi-square test was used to establish
      relationships between knowledge base factors and the uptake of breast cancer
      prevention modalities. RESULTS: This study has established an empirical
      relationship between uptake of breast cancer prevention modalities and source of
      information especially radio (OR 1.94 95% CI: 1.16-3.24), television (OR 1.82
      95%CI: 1.14-2.93), awareness of breast cancer (OR 4.03 95%CI: 1.01-15.98),
      knowledge on how to reduce risk of breast cancer (OR 1.98 95% CI: 1.20-3.27),
      what reduces breast cancer acquisition (OR 2.75 95% CI: 1.42-5.35), how to check
      for signs of breast cancer especially through breast self-examination (OR 3.09
      95% CI: 1.62-5.88), and other methods of breast cancer diagnosis in a health care
      set up. CONCLUSION: The women's level of breast cancer awareness as a primary
      prevention strategy was found wanting, and requires a boost through community
      health education.

PMID- 29471836
TI  - Differences in health literacy profiles of patients admitted to a public and a
      private hospital in Melbourne, Australia.
AB  - BACKGROUND: Health literacy refers to an individual's ability to find, understand
      and use health information in order to promote and maintain health. An
      individual's health literacy may also be influenced by the way health care
      organisations deliver care. The aim of this study was to investigate the
      influence of hospital service type (public versus private) on individual health
      literacy. METHODS: Two cross-sectional surveys were conducted using the Health
      Literacy Questionnaire (HLQ), a multi-dimensional self-report instrument covering
      nine health literacy domains. Recently discharged private patients (n = 3121)
      were sent the survey in English, public patients (n = 384) were sent the survey
      in English, Arabic, Chinese, Vietnamese, Italian or Greek. Eligibility included
      hospitalisation >=24 h in last 30 days, aged >=18 years, no cognitive impairment.
      Odds ratios were used to assess differences between hospital sociodemographic and
      health related variables. ANOVA and Cohen's effect sizes compared HLQ scores
      between hospitals. Chi square and multiple logistic regression were used to
      determine whether differences between private and public hospital HLQ scores was
      independent of hospital population sociodemographic differences. ANOVA was used
      to review associations between HLQ scores and subgroups of demographic, health
      behaviour and health conditions and these were then compared across the two
      hospital populations. RESULTS: Public hospital participants scored lower than
      private hospital participants on eight of the nine health literacy domains of the
      HLQ (scores for Active Appraisal did not differ between the two samples). Six
      domains, five of which in part measure the impact of how care is delivered on
      health literacy, remained lower among public hospital participants after
      controlling for age, education, language and income. Across both hospital
      populations, participants who were smokers, those who had low physical activity,
      those with depression and/or anxiety and those with 3 or more chronic conditions
      reported lower scores on some HLQ domains. CONCLUSIONS: Our finding of lower
      health literacy among patients who had received care at a public hospital in
      comparison to a private hospital, even after adjustment for sociodemographic and
      language differences, suggests that private hospitals may possess organisational
      attributes (environment, structure, values, practices and/or workforce
      competencies) that result in improved health literacy responsiveness.

PMID- 29471838
TI  - Impact assessment of Iran's health technology assessment programme.
AB  - BACKGROUND: Following approximately 10 years from the beginning of Iran's
      national Health Technology Assessment (HTA) programme, the present study aims to
      evaluate its success by examining the impact of HTA and identifying the
      determinant factors leading to the implementation of HTA report results. METHODS:
      The triangulation method was employed herein. HTA reports were initially
      identified and their impact and determinant factors were then examined from the
      perspectives of both researchers (by preparing a questionnaire according to the
      Payback model and sending it to HTA principle investigators) and stakeholders
      (semi-structured interviews held with each HTA stakeholder). Simultaneously, the
      quality of the HTA reports was examined with relevant critical appraisal
      checklists. RESULTS: The impact of 19 equipment technologies and four
      pharmaceutical technologies were assessed in this study. Twenty researchers
      replied (response rate, 86.96%) to the questionnaire on the impact of HTA reports
      from the researcher's perspective. To assess the impact of HTA reports from the
      stakeholder's perspective, seven policy-makers were chosen and interviewed as the
      main target audience. The most common step taken to disseminate the results of
      the HTA projects was publication. Conducting the HTA had taught researchers and
      their colleagues' new skills and had facilitated the securing of research grants
      from other organisations. Most reports had used the systematic review method but
      the relevant details had been scarcely presented regarding outcomes, costs and
      analysis. The greatest impact of HTA reports on decision-making had been on
      policy-makers providing and allocating finances. Barriers in stewardship,
      identification and prioritisation of topics, performance and dissemination of HTA
      results were the main barriers of implementing HTAs. CONCLUSIONS: In most
      aspects, the status of HTA impact reports need improvement. Thus far, the
      barriers and facilitators of the HTA programme in Iran have been investigated in
      other studies. These findings should be pooled to reach a solution that can be
      actively applied to the health system to improve the status quo of HTA in Iran.

PMID- 29471840
TI  - Designing evaluation studies to optimally inform policy: what factors do policy
      makers in China consider when making resource allocation decisions on healthcare
      worker training programmes?
AB  - BACKGROUND: In light of the gap in evidence to inform future resource allocation
      decisions about healthcare provider (HCP) training in low- and middle-income
      countries (LMICs), and the considerable donor investments being made towards
      training interventions, evaluation studies that are optimally designed to inform
      local policy-makers are needed. The aim of our study is to understand what
      features of HCP training evaluation studies are important for decision-making by
      policy-makers in LMICs. We investigate the extent to which evaluations based on
      the widely used Kirkpatrick model - focusing on direct outcomes of training,
      namely reaction of trainees, learning, behaviour change and improvements in
      programmatic health indicators - align with policy-makers' evidence needs for
      resource allocation decisions. We use China as a case study where resource
      allocation decisions about potential scale-up (using domestic funding) are being
      made about an externally funded pilot HCP training programme. METHODS:
      Qualitative data were collected from high-level officials involved in resource
      allocation at the national and provincial level in China through ten face-to
      face, in-depth interviews and two focus group discussions consisting of ten
      participants each. Data were analysed manually using an interpretive thematic
      analysis approach. RESULTS: Our study indicates that Chinese officials not only
      consider information about the direct outcomes of a training programme, as
      captured in the Kirkpatrick model, but also need information on the resources
      required to implement the training, the wider or indirect impacts of training,
      and the sustainability and scalability to other settings within the country. In
      addition to considering findings presented in evaluation studies, we found that
      Chinese policy-makers pay close attention to whether the evaluations were robust
      and to the composition of the evaluation team. CONCLUSIONS: Our qualitative study
      indicates that training programme evaluations that focus narrowly on direct
      training outcomes may not provide sufficient information for policy-makers to
      make decisions on future training programmes. Based on our findings, we have
      developed an evidence-based framework, which incorporates but expands beyond the
      Kirkpatrick model, to provide conceptual and practical guidance that aids in the
      design of training programme evaluations better suited to meet the information
      needs of policy-makers and to inform policy decisions.

PMID- 29471839
TI  - Controlled Education of patients after Stroke (CEOPS)- nurse-led multimodal and
      long-term interventional program involving a patient's caregiver to optimize
      secondary prevention of stroke: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Setting up a follow-up secondary prevention program after stroke is
      difficult due to motor and cognitive impairment, but necessary to prevent
      recurrence and improve patients' quality of life. To involve a referent nurse and
      a caregiver from the patient's social circle in nurse-led multimodal and long
      term management of risk factors after stroke could be an advantage due to their
      easier access to the patient and family. The aim of this study is to compare the
      benefit of optimized follow up by nursing personnel from the vascular neurology
      department including therapeutic follow up, and an interventional program
      directed to the patient and a caregiving member of their social circle, as
      compared with typical follow up in order to develop a specific follow-up program
      of secondary prevention of stroke. METHODS/DESIGN: The design is a randomized,
      controlled, clinical trial conducted in the French Stroke Unit of the Strokavenir
      network. In total, 410 patients will be recruited and randomized in optimized
      follow up or usual follow up for 2 years. In both group, patients will be seen by
      a neurologist at 6, 12 and 24 months. The optimized follow up will include follow
      up by a nurse from the vascular neurology department, including therapeutic
      follow up, and a training program on secondary prevention directed to the patient
      and a caregiving member of their social circle. After discharge, a monthly
      telephone interview, in the first year and every 3 months in the second year,
      will be performed by the nurse. At 6, 12 and 24 month, the nurse will give the
      patient and caregiver another training session. Usual follow up is only done by
      the patient's general practitioner, after classical information on secondary
      prevention of risk factors during hospitalization. The primary outcome measure is
      blood pressure measured after the first year of follow up. Blood pressure will be
      measured by nursing personnel who do not know the group into which the patient
      has been randomized. Secondary endpoints are associated mortality, morbidity,
      recurrence, drug side-effects and medico-economic analysis. DISCUSSION: The
      result of this trial is expected to provide the benefit of a nurse-led optimized
      multimodal and long-term interventional program for management of risk factors
      after stroke, personalizing the role of the nurse and including the patient's
      caregiver. TRIAL REGISTRATION: ClinicalTrials.gov, NCT 02132364. Registered on 7
      May 2014. EUDRACT, A 00473-40.

PMID- 29471841
TI  - Artificial oxygen carriers: a new future?

PMID- 29471842
TI  - Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer's disease
      in wild-type, C57BL/6 mice.
AB  - BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease
      associated with cognitive decline and complete loss of basic functions. The
      ubiquitous apicomplexan parasite Toxoplasma gondii (T. gondii) infects up to one
      third of the world's population and is implicated in AD. METHODS: We infected
      C57BL/6 wild-type male and female mice with 10 T. gondii ME49 cysts and assessed
      whether infection led to behavioral and anatomical effects using
      immunohistochemistry, immunofluorescence, Western blotting, cell culture assays,
      as well as an array of mouse behavior tests. RESULTS: We show that T. gondii
      infection induced two major hallmarks of AD in the brains of C57BL/6 male and
      female mice: beta-amyloid (Abeta) immunoreactivity and hyperphosphorylated Tau.
      Infected mice showed significant neuronal death, loss of N-methyl-D-aspartate
      receptor (NMDAR) expression, and loss of olfactory sensory neurons. T. gondii
      infection also caused anxiety-like behavior, altered recognition of social
      novelty, altered spatial memory, and reduced olfactory sensitivity. This last
      finding was exclusive to male mice, as infected females showed intact olfactory
      sensitivity. CONCLUSIONS: These results demonstrate that T. gondii can induce
      advanced signs of AD in wild-type mice and that it may induce AD in some
      individuals with underlying health problems.

PMID- 29471843
TI  - Prevalence and phylogenetic analysis of hepatitis E virus in pigs, wild boars,
      roe deer, red deer and moose in Lithuania.
AB  - BACKGROUND: Hepatitis E virus (HEV) is one of the major causes of acute viral
      hepatitis worldwide. In Europe, food-borne zoonotic transmission of HEV genotype
      3 has been associated with domestic pigs and wild boar. Controversial data are
      available on the circulation of the virus in animals that are used for human
      consumption, and to date, no gold standard has yet been defined for the diagnosis
      of HEV-associated hepatitis. To investigate the current HEV infection status in
      Lithuanian pigs and wild ungulates, the presence of viral RNA was analyzed by
      nested reverse transcription polymerase chain reaction (RT-nPCR) in randomly
      selected samples, and the viral RNA was subsequently genotyped. RESULTS: In
      total, 32.98 and 22.55% of the domestic pig samples were HEV-positive using RT
      nPCR targeting the ORF1 and ORF2 fragments, respectively. Among ungulates, 25.94%
      of the wild boar samples, 22.58% of the roe deer samples, 6.67% of the red deer
      samples and 7.69% of the moose samples were positive for HEV RNA using primers
      targeting the ORF1 fragment. Using primers targeting the ORF2 fragment of the HEV
      genome, viral RNA was only detected in 17.03% of the wild boar samples and 12.90%
      of the roe deer samples. Phylogenetic analysis based on a 348-nucleotide-long
      region of the HEV ORF2 showed that all obtained sequences detected in Lithuanian
      domestic pigs and wildlife belonged to genotype 3. In this study, the sequences
      identified from pigs, wild boars and roe deer clustered within the 3i subtype
      reference sequences from the GenBank database. The sequences obtained from pig
      farms located in two different counties of Lithuania were of the HEV 3f subtype.
      The wild boar sequences clustered within subtypes 3i and 3h, clearly indicating
      that wild boars can harbor additional subtypes of HEV. For the first time, the
      ORF2 nucleotide sequences obtained from roe deer proved that HEV subtype 3i can
      be found in a novel host. CONCLUSION: The results of the viral prevalence and
      phylogenetic analyses clearly demonstrated viral infection in Lithuanian pigs and
      wild ungulates, thus highlighting a significant concern for zoonotic virus
      transmission through both the food chain and direct contact with animals.
      Unexpected HEV genotype 3 subtype diversity in Lithuania and neighboring
      countries revealed that further studies are necessary to understand the mode of
      HEV transmission between animals and humans in the Baltic States region.

PMID- 29471844
TI  - Spatiotemporal patterns and environmental drivers of human echinococcoses over a
      twenty-year period in Ningxia Hui Autonomous Region, China.
AB  - BACKGROUND: Human cystic (CE) and alveolar (AE) echinococcoses are zoonotic
      parasitic diseases that can be influenced by environmental variability and change
      through effects on the parasites, animal intermediate and definitive hosts, and
      human populations. We aimed to assess and quantify the spatiotemporal patterns of
      human echinococcoses in Ningxia Hui Autonomous Region (NHAR), China between
      January 1994 and December 2013, and examine associations between these infections
      and indicators of environmental variability and change, including large-scale
      landscape regeneration undertaken by the Chinese authorities. METHODS: Data on
      the number of human echinococcosis cases were obtained from a hospital-based
      retrospective survey conducted in NHAR for the period 1 January 1994 through 31
      December 2013. High-resolution imagery from Landsat 4/5-TM and 8-OLI was used to
      create single date land cover maps. Meteorological data were also collected for
      the period January 1980 to December 2013 to derive time series of bioclimatic
      variables. A Bayesian spatio-temporal conditional autoregressive model was used
      to quantify the relationship between annual cases of CE and AE and environmental
      variables. RESULTS: Annual CE incidence demonstrated a negative temporal trend
      and was positively associated with winter mean temperature at a 10-year lag.
      There was also a significant, nonlinear effect of annual mean temperature at 13
      year lag. The findings also revealed a negative association between AE incidence
      with temporal moving averages of bareland/artificial surface coverage and annual
      mean temperature calculated for the period 11-15 years before diagnosis and
      winter mean temperature for the period 0-4 years. Unlike CE risk, the selected
      environmental covariates accounted for some of the spatial variation in the risk
      of AE. CONCLUSIONS: The present study contributes towards efforts to understand
      the role of environmental factors in determining the spatial heterogeneity of
      human echinococcoses. The identification of areas with high incidence of CE and
      AE may assist in the development and refinement of interventions for these
      diseases, and enhanced environmental change risk assessment.

PMID- 29471845
TI  - Association of the client-provider ratio with the risk of maternal mortality in
      referral hospitals: a multi-site study in Nigeria.
AB  - BACKGROUND: The paucity of human resources for health buoyed by excessive
      workloads has been identified as being responsible for poor quality obstetric
      care, which leads to high maternal mortality in Nigeria. While there is anecdotal
      and qualitative research to support this observation, limited quantitative
      studies have been conducted to test the association between the number and
      density of human resources and risk of maternal mortality. This study aims to
      investigate the association between client-provider ratios for antenatal and
      delivery care and the risk of maternal mortality in 8 referral hospitals in
      Nigeria. METHODS: Client-provider ratios were calculated for antenatal and
      delivery care attendees during a 3-year period (2011-2013). The maternal
      mortality ratio (MMR) was calculated per 100,000 live births for the hospitals,
      while unadjusted Poisson regression analysis was used to examine the association
      between the number of maternal deaths and density of healthcare providers.
      RESULTS: A total of 334,425 antenatal care attendees and 26,479 births were
      recorded during this period. The client-provider ratio in the maternity
      department for antenatal care attendees was 1343:1 for doctors and 222:1 for
      midwives. The ratio of births to one doctor in the maternity department was 106:1
      and 18:1 for midwives. On average, there were 441 births per specialist
      obstetrician. The results of the regression analysis showed a significant
      negative association between the number of maternal deaths and client-provider
      ratios in all categories. CONCLUSION: We conclude that the maternal mortality
      ratios in Nigeria's referral hospitals are worsened by high client-provider
      ratios, with few providers attending a large number of pregnant women. Efforts to
      improve the density and quality of maternal healthcare providers, especially at
      the first referral level, would be a critical intervention for reducing the
      currently high rate of maternal mortality in Nigeria. TRIAL REGISTRATION: Trial
      Registration Number: NCTR91540209 . Nigeria Clinical Trials Registry. Registered
      14 April 2016.

PMID- 29471846
TI  - Understanding nurses' dual practice: a scoping review of what we know and what we
      still need to ask on nurses holding multiple jobs.
AB  - BACKGROUND: Mounting evidence suggests that holding multiple concurrent jobs in
      public and private (dual practice) is common among health workers in low- as well
      as high-income countries. Nurses are world's largest health professional
      workforce and a critical resource for achieving Universal Health Coverage.
      Nonetheless, little is known about nurses' engagement with dual practice.
      METHODS: We conducted a scoping review of the literature on nurses' dual practice
      with the objective of generating hypotheses on its nature and consequences, and
      define a research agenda on the phenomenon. The Arksey and O'Malley's
      methodological steps were followed to develop the research questions, identify
      relevant studies, include/exclude studies, extract the data, and report the
      findings. PRISMA guidelines were additionally used to conduct the review and
      report on results. RESULTS: Of the initial 194 records identified, a total of 35
      met the inclusion criteria for nurses' dual practice; the vast majority (65%)
      were peer-reviewed publications, followed by nursing magazine publications (19%),
      reports, and doctoral dissertations. Twenty publications focused on high-income
      countries, 16 on low- or middle-income ones, and two had a multi country
      perspective. Although holding multiple jobs not always amounted to dual practice,
      several ways were found for public-sector nurses to engage concomitantly in
      public and private employments, in regulated as well as in informal, casual
      fashions. Some of these forms were reported as particularly prevalent, from over
      50% in Australia, Canada, and the UK, to 28% in South Africa. The opportunity to
      increase a meagre salary, but also a dissatisfaction with the main job and the
      flexibility offered by multiple job-holding arrangements, were among the reported
      reasons for engaging in these practices. DISCUSSION AND CONCLUSIONS: Limited and
      mostly circumstantial evidence exists on nurses' dual practice, with the few
      existing studies suggesting that the phenomenon is likely to be very common and
      carry  implications for health systems and nurses' welfare worldwide. We offer an
      agenda for future research to consolidate the existing evidence and to further
      explore nurses' motivation; without a better understanding of nurse dual
      practice, this will continue to be a largely 'hidden' element in nursing
      workforce policy and practice, with an unclear impact on the delivery of care.

PMID- 29471847
TI  - The impact of metallothionein-II on microglial response to tumor necrosis factor
      alpha (TNFalpha) and downstream effects on neuronal regeneration.
AB  - BACKGROUND: The extracellular environment plays an important role in supporting
      the regeneration of axons after injury. Metallothionein-II (MTII) is a metal
      binding protein known for its neuroprotective effect by directly stimulating the
      growth of axons after injury. Previous studies have shown that MTII also
      modulates the response of astrocytes and microglia after injury. However, a
      detailed analysis describing how MTII modulates the interaction between microglia
      and neurons is lacking. METHODS: We introduced fluorescently labelled MTII into
      the cortex at the time of needlestick injury to investigate the cellular uptake
      of MTII using immunohistochemistry with antibodies against cell-type-specific
      markers. The role of MTII in modulating the effect of microglia on axon outgrowth
      following an inflammatory response is further investigated using a co-culture
      model involving primary rodent microglia pre-treated with TNFalpha and primary
      rodent cortical neurons. The axon lengths were assessed 24 h after the plating of
      the neurons onto treated microglia. We also utilised siRNA to knockdown the
      expression of LRP1, which allows us to investigate the role of LRP1 receptors in
      the MTII-mediated effect of microglia on axon outgrowth. RESULTS: Fluorescently
      labelled MTII was found to be associated with neurons, astrocytes and microglia
      following injury in vivo. Microglia-neuron co-culture experiments demonstrated
      that exogenous MTII altered the response of microglia to TNFalpha. The neurons
      plated onto the TNFalpha-stimulated microglia pre-treated with MTII have shown a
      significantly longer axonal length compare to the TNFalpha-stimulated microglia
      without the MTII treatment. This suggested that MTII reduce cytokine-stimulated
      activation of microglia, which would ordinarily impair neurite outgrowth. This
      inhibitory effect of MTII on activated microglia was blocked by siRNA-mediated
      downregulation of LRP1 receptor expression in microglia, suggesting that MTII
      acts via the LRP1 receptor on microglia. CONCLUSIONS: This study demonstrates
      that exogenous MTII acts via the LRP1 receptor to alter the inflammatory response
      of microglia following TNFalpha stimulation, providing a more supportive
      environment for axon growth.

PMID- 29471848
TI  - Canine caliciviruses of four serotypes from military and research dogs recovered
      in 1963-1978 belong to two phylogenetic clades in the Vesivirus genus.
AB  - BACKGROUND: Vesiviruses (family Caliciviridae) had been shown capable of invading
      a variety of host species, raising concern of their zoonotic potential. Since the
      1980's, several canine caliciviruses (CaCV) isolates have been reported and are
      phylogenetically related to the vesiviruses with features distinct from both
      Vesicular exanthema of swine virus (VESV) and Feline calicivirus (FCV) species in
      phylogeny, serology and cell culture specificities. Etiological studies of canine
      diseases in dogs used for military services and laboratory studies were conducted
      in 1963-1978 at the Walter Reed Army Institute of Research. Multiple known and
      unknown viral pathogens including caliciviruses were recovered. METHODS: Four
      unidentified isolates were recovered in Walter Reed Canine Cells (WRCC) from
      respiratory, fecal and penile specimens. Physicochemical tests, electron
      microscopy, viral cultivation in human and animal cells, antibody neutralization
      assays, and recently the genome sequencing were used to characterize the
      isolates. Sera from these dogs and their cohorts were tested with the isolates to
      determine origin and prevalence of the infections. RESULTS: The viral isolates
      were small non-enveloped spherical RNA virions, 27 to 42 nm in diameter with cup
      like structures, indicating they are caliciviruses. They propagated in WRCC and
      MDCK cells, not in either other canine cells or human and other animal cells.
      Each isolate is antigenically distinct and react with dog sera in respective
      cohorts. The genomes have nucleotide identities ranging from 70.3% to 90.7% and
      encode the non-structural polyprotein (1810 amino acids), major capsid protein
      (691 amino acids) and minor structural protein (134 amino acids). They belong to
      two different phylogenetic clades in Vesivirus genus with close relation with
      canine calicivirus (CaCV). CONCLUSIONS: These CaCV isolates have restricted cell
      tropism, antigenic diversity and genetic variation. Further investigation will
      shed light on antigenic relation to other vesiviruses, and its pathogenicity for
      dogs and potential infectivity to other animals. Together with the previously
      reported CaCV strains provides significant evidence to support the formation of a
      new CaCV species in the Vesivirus genus.

PMID- 29471849
TI  - Implementing Alcohol Misuse SBIRT in a National Cohort of Pediatric Trauma
      Centers-a type III hybrid effectiveness-implementation trial.
AB  - BACKGROUND: The American College of Surgeons mandates universal screening for
      alcohol misuse and delivery of an intervention for those screening positive as a
      requirement for certification as a level 1 trauma center. Though this requirement
      has been mandated for over a decade, its implementation has been challenging. Our
      research team completed an implementation study supporting seven pediatric trauma
      centers' compliance with the requirement by developing and implementing an
      institutional alcohol Screening, Brief Intervention and Referral to Treatment
      (SBIRT) policy for adolescent trauma patients. A mixed-methods approach indicated
      that SBIRT adoption rates increased at all sites; however, providers' fidelity to
      the SBIRT intervention was variable, and providers reported a number of barriers
      to SBIRT implementation. The goal of this study is to conduct a fully powered
      type III hybrid effectiveness-implementation trial to test the effectiveness of a
      comprehensive implementation strategy in increasing the implementation of SBIRT
      for alcohol and other drug use (AOD) in pediatric trauma centers. METHODS: Our
      implementation strategy is based on the Science to Service Laboratory (SSL), an
      approach developed by the SAMHSA-funded Addiction Technology Transfer Centers
      that consists of three core elements (i.e., didactic training + performance
      feedback + leadership coaching). Utilizing a stepped wedge design, a national
      cohort of 10 pediatric trauma centers will receive the SSL implementation
      strategy. At six distinct time points, each of the 10 sites will provide data
      from 30 electronic medical records (n = 1800 in total). A subset of adolescents
      will also report on fidelity of intervention delivery and linkage to care (i.e.,
      continued AOD discussion and/or treatment with a primary care provider) 1 month
      after hospital discharge. In addition, nurses, social workers, and leaders will
      report on organizational readiness for implementation at four distinct time
      points. DISCUSSION: This protocol proposes a unique opportunity to examine
      whether a comprehensive implementation strategy can improve the fidelity of SBIRT
      delivery across a national cohort of pediatric trauma centers. With injured
      adolescents, this could optimize the detection and intervention of AOD use and
      improve adolescent health. TRIAL REGISTRATION: Clinicaltrials.gov NCT03297060 .

PMID- 29471850
TI  - Taliglucerase alfa: safety and efficacy across 6 clinical studies in adults and
      children with Gaucher disease.
AB  - Taliglucerase alfa is an enzyme replacement therapy (ERT) approved for treatment
      of adult and paediatric patients with Type 1 Gaucher disease (GD) in several
      countries and the first plant cell-expressed recombinant therapeutic protein
      approved by the US Food and Drug Administration for humans. Here, we review the
      findings across six key taliglucerase alfa clinical studies. A total of 33
      treatment-naive adult patients were randomized to taliglucerase alfa 30 U/kg or
      60 U/kg in a 9-month, multicentre, randomized, double-blind, parallel-group, dose
      comparison pivotal study, after which eligible patients continued into two
      consecutive extension studies; 17 treatment-naive adult patients completed 5
      total years of treatment with taliglucerase alfa. In the only ERT study focused
      on exclusively paediatric patients with GD, 11 treatment-naive children were
      randomized to taliglucerase alfa 30 U/kg or 60 U/kg in a 12-month, multicentre,
      double-blind study; nine completed 3 total years of treatment in a dedicated
      paediatric extension study. The effect of switching patients from imiglucerase to
      taliglucerase alfa was also investigated in a separate 9-month study that
      included 26 adults and five children; 10 adults completed a total of 3 years and
      two children completed a total of 2.75 years of taliglucerase alfa treatment in
      the extension studies. All studies evaluated safety and spleen volume, liver
      volume, platelet count, haemoglobin concentration, and biomarkers as measures of
      efficacy. Detailed results from baseline through the end of these studies are
      presented. Taliglucerase alfa was well tolerated, and adverse events were
      generally mild/moderate in severity and transient. Treatment with taliglucerase
      alfa resulted in improvements (treatment-naive patients) or stability (patients
      switched from imiglucerase) in visceral, haematologic, and biomarker parameters.
      Together, this comprehensive data set supports the treatment of adult and
      paediatric patients with GD who are naive to ERT or who have previously been
      treated with imiglucerase.

PMID- 29471851
TI  - Multilocus sequence typing: genetic diversity in Trypanosoma cruzi I (TcI)
      isolates from Brazilian didelphids.
AB  - BACKGROUND: Trypanosoma cruzi is a protozoan parasite characterized by extensive
      genetic heterogeneity. There are currently six recognised, genetically distinct,
      monophyletic clades designated discrete typing units (DTUs). TcI has the broadest
      geographical range and most genetic diversity evidenced by a wide range of
      genetic markers applied to isolates spanning a vast geographical range across
      Latin America. However, little is known of the diversity of TcI that exists
      within sylvatic mammals across the geographical expanse of Brazil. RESULTS:
      Twenty-nine sylvatic TcI isolates spanning multiple ecologically diverse biomes
      across Brazil were analyzed by the application of multilocus sequence typing
      (MLST) using four nuclear housekeeping genes. Results revealed extensive genetic
      diversity and also incongruence among individual gene trees. There was no
      association of intralineage genotype with geography or with any particular biome,
      with the exception of isolates from Caatinga that formed a single cluster.
      However, haplotypic analyses of METIII and LYT1 constitutive markers provided
      evidence of recombination events in two isolates derived from Didelphis
      marsupialis and D. albiventris, respectively. For diversity studies all possible
      combinations of markers were assessed with the objective of selecting the
      combination of gene targets that are most resolutive using the minimum number of
      genes. A panel of just three gene fragments (DHFR-TS, LYT1 and METIII)
      discriminated 26 out of 35 genotypes. CONCLUSIONS: These findings showed
      geographical association of genotypes clustering in Caatinga but more
      characteristically TcI genotypes widely distributed without specific association
      to geographical areas or biomes. Importantly, we detected the signature of
      recombination events at the nuclear level evidenced by haplotypic analysis and
      incongruence.

PMID- 29471852
TI  - CDK9 inhibitors in acute myeloid leukemia.
AB  - Current treatment for acute myeloid leukemia (AML) is less than optimal, but
      increased understanding of disease pathobiology and genomics has led to clinical
      investigation of novel targeted therapies and rational combinations. Targeting
      the cyclin-dependent kinase 9 (CDK9) pathway, which is dysregulated in AML, is an
      attractive approach. Inhibition of CDK9 leads to downregulation of cell survival
      genes regulated by super enhancers such as MCL-1, MYC, and cyclin D1. As CDK9
      inhibitors are nonselective, predictive biomarkers that may help identify
      patients most likely to respond to CDK9 inhibitors are now being utilized, with
      the goal of improving efficacy and safety.

PMID- 29471853
TI  - Oncoprotein HBXIP enhances HOXB13 acetylation and co-activates HOXB13 to confer
      tamoxifen resistance in breast cancer.
AB  - BACKGROUND: Resistance to tamoxifen (TAM) frequently occurs in the treatment of
      estrogen receptor positive (ER+) breast cancer. Accumulating evidences indicate
      that transcription factor HOXB13 is of great significance in TAM resistance.
      However, the regulation of HOXB13 in TAM-resistant breast cancer remains largely
      unexplored. Here, we were interested in the potential effect of HBXIP, an
      oncoprotein involved in the acceleration of cancer progression, on the modulation
      of HOXB13 in TAM resistance of breast cancer. METHODS: The Kaplan-Meier plotter
      cancer database and GEO dataset were used to analyze the association between
      HBXIP expression and relapse-free survival. The correlation of HBXIP and HOXB13
      in ER+ breast cancer was assessed by human tissue microarray. Immunoblotting
      analysis, qRT-PCR assay, immunofluorescence staining, Co-IP assay, ChIP assay,
      luciferase reporter gene assay, cell viability assay, and colony formation assay
      were performed to explore the possible molecular mechanism by which HBXIP
      modulates HOXB13. Cell viability assay, xenograft assay, and immunohistochemistry
      staining analysis were utilized to evaluate the effect of the HBXIP/HOXB13 axis
      on the facilitation of TAM resistance in vitro and in vivo. RESULTS: The analysis
      of the Kaplan-Meier plotter and the GEO dataset showed that mono-TAM-treated
      breast cancer patients with higher HBXIP expression levels had shorter relapse
      free survivals than patients with lower HBXIP expression levels. Overexpression
      of HBXIP induced TAM resistance in ER+ breast cancer cells. The tissue microarray
      analysis revealed a positive association between the expression levels of HBXIP
      and HOXB13 in ER+ breast cancer patients. HBXIP elevated HOXB13 protein level in
      breast cancer cells. Mechanistically, HBXIP prevented chaperone-mediated
      autophagy (CMA)-dependent degradation of HOXB13 via enhancement of HOXB13
      acetylation at the lysine 277 residue, causing the accumulation of HOXB13.
      Moreover, HBXIP was able to act as a co-activator of HOXB13 to stimulate
      interleukin (IL)-6 transcription in the promotion of TAM resistance.
      Interestingly, aspirin (ASA) suppressed the HBXIP/HOXB13 axis by decreasing HBXIP
      expression, overcoming TAM resistance in vitro and in vivo. CONCLUSIONS: Our
      study highlights that HBXIP enhances HOXB13 acetylation to prevent HOXB13
      degradation and co-activates HOXB13 in the promotion of TAM resistance of breast
      cancer. Therapeutically, ASA can serve as a potential candidate for reversing TAM
      resistance by inhibiting HBXIP expression.

PMID- 29471855
TI  - Phase-based treatment versus immediate trauma-focused treatment in patients with
      childhood trauma-related posttraumatic stress disorder: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: The treatment of posttraumatic stress disorder (PTSD) related to a
      history of sexual and/or physical abuse in childhood is the subject of
      international debate, with some favouring a phase-based approach as their
      preferred treatment, while others argue for immediate trauma-focused treatment. A
      history of (chronic) traumatisation during childhood has been linked to the
      development of distinct symptoms that are often labelled as symptoms of complex
      PTSD. Many therapists associate the presence of symptoms of complex PTSD with a
      less favourable treatment prognosis. The purpose of this study is to determine
      whether a phase-based approach is more effective than stand-alone trauma-focused
      therapy in individuals with PTSD and possible symptoms of complex PTSD resulting
      from a history of repeated sexual and/or physical abuse in childhood. An
      additional aim is to investigate moderators, predictors of treatment (non)
      response and drop-out. METHOD: The sample consists of patients between 18 and 65
      years old with a diagnosis of PTSD who report a history of repeated sexual and/or
      physical abuse in childhood (N = 122). Patients will be blindly allocated to
      either 16 sessions of eye movement desensitization and reprocessing (EMDR)
      therapy preceded by a stabilization phase (eight sessions of Skills Training in
      Affect and Interpersonal Regulation (STAIR)) or only 16 sessions of EMDR therapy.
      Assessments are carried out pre-treatment, after every eighth session, post
      treatment, and at 3 and 6 months follow up. The main parameter will be the
      severity of PTSD symptoms (PTSD Symptoms Scale-Self Report). Secondary outcome
      variables are the presence of a PTSD diagnosis (Clinician-Administered PTSD Scale
      for DSM-5), severity of complex PTSD symptoms (Structured Interview for Disorders
      of Extreme Stress-Revised and symptoms-specific questionnaires), changes in
      symptoms of general psychopathology (Brief Symptom Inventory), and quality of
      life (Euroqol-5D). Health care consumption and productivity loss in patients will
      also be indexed. DISCUSSION: The study results may help to inform the ongoing
      debate about whether a phase-based approach has added value over immediate trauma
      focused therapy in patients suffering from PTSD due to childhood abuse.
      Furthermore, the results will contribute to knowledge about the safety, efficacy,
      and cost-effectiveness of treatments in this target group. TRIAL REGISTRATION:
      Nederlands Trialregister, NTR5991 . Registered on 23 august 2016.
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5991.

PMID- 29471854
TI  - Recent advances in retroviruses via cryo-electron microscopy.
AB  - Cryo-electron microscopy has undergone a revolution in recent years and it has
      contributed significantly to a number of different areas in biological research.
      In this manuscript, we will describe some of the recent advancements in cryo
      electron microscopy focussing on the advantages that this technique can bring
      rather than on the technology. We will then conclude discussing how the field of
      retrovirology has benefited from cryo-electron microscopy.

PMID- 29471856
TI  - Quantitative cardiovascular magnetic resonance perfusion imaging identifies
      reduced flow reserve in microvascular coronary artery disease.
AB  - BACKGROUND: Preliminary semi-quantitative cardiovascular magnetic resonance (CMR)
      perfusion studies have demonstrated reduced myocardial perfusion reserve (MPR) in
      patients with angina and risk factors for microvascular disease (MVD), however
      fully quantitative CMR has not been studied. The purpose of this study is to
      evaluate whether fully quantitative CMR identifies reduced MPR in this
      population, and to investigate the relationship between epicardial
      atherosclerosis, left ventricular hypertrophy (LVH), extracellular volume (ECV),
      and perfusion. METHODS: Forty-six patients with typical angina and risk factors
      for MVD (females, or males with diabetes or metabolic syndrome) who had no
      obstructive coronary artery disease by coronary angiography and 20 healthy
      control subjects underwent regadenoson stress CMR perfusion imaging using a dual
      sequence quantitative spiral pulse sequence to quantify MPR. Subjects also
      underwent T1 mapping to quantify ECV, and computed tomographic (CT) coronary
      calcium scoring to assess atherosclerosis burden. RESULTS: In patients with risk
      factors for MVD, both MPR (2.21 [1.95,2.69] vs. 2.93 [2.763.19], p < 0.001) and
      stress myocardial perfusion (2.65 +/- 0.62 ml/min/g, vs. 3.17 +/- 0.49 ml/min/g p
      < 0.002) were reduced as compared to controls. These differences remained after
      adjusting for age, left ventricular (LV) mass, body mass index (BMI), and gender.
      There were no differences in native T1 or ECV between subjects and controls.
      CONCLUSIONS: Stress myocardial perfusion and MPR as measured by fully
      quantitative CMR perfusion imaging are reduced in subjects with risk factors for
      MVD with no obstructive CAD as compared to healthy controls. Neither myocardial
      hypertrophy nor fibrosis accounts for these differences.

PMID- 29471858
TI  - Tumor-promoting properties of miR-8084 in breast cancer through enhancing
      proliferation, suppressing apoptosis and inducing epithelial-mesenchymal
      transition.
AB  - BACKGROUND: Breast cancer is one of the most frequent malignancies and the second
      leading cause of cancer-related mortality in women. MicroRNAs play a key role in
      breast cancer development and progression. microRNA(miR)-8084 has been observed
      an aberrant expression in breast cancer. However, the functions and regulatory
      axes of miR-8084, particularly in breast cancer, were not entirely clear.
      METHODS: miR-8084 expression in breast cancer were investigated in a GEO dataset
      by in silico analysis and in 42 paired tumor tissues by qPCR. The effects of
      deregulation of miR-8084 on breast cancer cell proliferation, migration and
      invasion in vitro and tumorigenicity in vivo were examined by colony-formation
      assay, wound healing assay, transwell assay and nude mouse subcutaneous tumor
      formation model. The target gene of miR-8084 were predicted by TargetScan and
      miRDB, and confirmed by luciferase reporter system. The roles of miR-8084 in the
      breast cancer cell proliferation, apoptosis and epithelial-mesenchymal transition
      (EMT) were investigated by MTS, FACS and associated-marker detection by western
      blot. RESULTS: miR-8084 is significantly up-regulated in both serum and malignant
      tissues from the source of breast cancer patients. miR-8084 promotes the
      proliferation of breast cancer cells by activating ERK1/2 and AKT. Meanwhile miR
      8084 inhibits apoptosis by decreasing p53-BAX related pathway. miR-8084 also
      enhances migration and invasion by inducing EMT. Moreover, the tumor suppressor
      ING2 is a potential target of miR-8084, and miR-8084 regulatory axes contribute
      to pro-tumor effect, at least partially through regulating ING2. CONCLUSION: Our
      results strongly suggest that miR-8084 functions as an oncogene that promotes the
      development and progression of breast cancer, and miR-8084 is a potential new
      diagnostic marker and therapeutic target of breast cancer.

PMID- 29471857
TI  - Patterns of Midichloria infection in avian-borne African ticks and their trans
      Saharan migratory hosts.
AB  - BACKGROUND: Ticks are obligate haematophagous ectoparasites of vertebrates and
      frequently parasitize avian species that can carry them across continents during
      their long-distance migrations. Ticks may have detrimental effects on the health
      state of their avian hosts, which can be either directly caused by blood-draining
      or mediated by microbial pathogens transmitted during the blood meal. Indeed,
      ticks host complex microbial communities, including bacterial pathogens and
      symbionts. Midichloria bacteria (Rickettsiales) are widespread tick endosymbionts
      that can be transmitted to vertebrate hosts during the tick bite, inducing an
      antibody response. Their actual role as infectious/pathogenic agents is, however,
      unclear. METHODS: We screened for Midichloria DNA African ticks and blood samples
      collected from trans-Saharan migratory songbirds at their arrival in Europe
      during spring migration. RESULTS: Tick infestation rate was 5.7%, with most ticks
      belonging to the Hyalomma marginatum species complex. Over 90% of Hyalomma ticks
      harboured DNA of Midichloria bacteria belonging to the monophylum associated with
      ticks. Midichloria DNA was detected in 43% of blood samples of avian hosts. Tick
      infested adult birds were significantly more likely to test positive to the
      presence of Midichloria DNA than non-infested adults and second-year individuals,
      suggesting a long-term persistence of these bacteria within avian hosts. Tick
      parasitism was associated with a significantly delayed timing of spring migration
      of avian hosts but had no significant effects on body condition, whereas blood
      Midichloria DNA presence negatively affected fat deposits of tick-infested avian
      hosts. CONCLUSIONS: Our results show that ticks effectively transfer Midichloria
      bacteria to avian hosts, supporting the hypothesis that they are infectious to
      vertebrates. Bird infection likely enhances the horizontal spread of these
      bacteria across haematophagous ectoparasite populations. Moreover, we showed that
      Midichloria and tick parasitism have detrimental non-independent effects on avian
      host health during migration, highlighting the complexity of interactions
      involving ticks, their vertebrate hosts, and tick-borne bacteria.

PMID- 29471859
TI  - Impact of time-related factors on biologically accurate radiotherapy treatment
      planning.
AB  - BACKGROUND: The incomplete repair (IR) model expresses the cell repair effect
      from radiation-induced damage over time, which is given little consideration in
      actual treatment planning. By incorporating the IR model into the normal tissue
      complication probability (NTCP), the accuracy and safety of treatment plan
      evaluations concerning the effect of repair can be improved. This study aims to
      evaluate the impact of incorporating the IR model into the NTCP by varying time
      related factors such as the repair half-time (T1/2) and the junction-shift
      sc3hedule in craniospinal irradiation (CSI). METHODS: CSI was planned
      retrospectively, and the NTCP of the spinal cord was calculated with the IR model
      for values of T1/2 from 1 to 10 h. The NTCP in the case of changing the junction
      shift schedule was also examined in the same manner. RESULTS: The NTCP with the
      IR model increased with increasing T1/2, which is prominent for the larger T1/2.
      By changing the junction-shift schedule, the NTCP with the IR model decreased
      when adjacent fields overlapped. CONCLUSIONS: The IR model is a valuable addition
      to treatment planning because it enables the NTCP to be evaluated including the
      effect of repair and differences in scheduling to be reflected in the NTCP.
      However, these are largely dependent on the value of the T1/2.

PMID- 29471860
TI  - Urinary phthalate metabolites in relation to serum anti-Mullerian hormone and
      inhibin B levels among women from a fertility center: a retrospective analysis.
AB  - BACKGROUND: Phthalates, a class of endocrine disruptors, have been demonstrated
      to accelerate loss of ovarian follicle pool via disrupting folliculogenesis, and
      lead to diminished ovarian reserve. However, human data are limited. Here, we
      aimed to examine whether urinary phthalate metabolites are correlated with
      markers of ovarian reserve among women attending a fertility clinic. METHODS: We
      measured eight phthalate metabolites in urine samples collected from 415 women
      seeking infertility treatment at the Reproductive Medicine Center of Tongji
      Hospital, Wuhan, China. Data on measures of ovarian reserve, as indicated by
      serum anti-Mullerian hormone (AMH) and inhibin B (INHB) levels, were retrieved
      retrospectively through electronic medical charts. Multivariate linear models
      were performed to estimate the associations of urinary phthalate metabolites and
      serum AMH and INHB. We further explored the potential nonlinearity of the
      relationships with restricted cubic spline analysis. RESULTS: Overall, we found
      largely null associations between urinary phthalate metabolites and serum AMH.
      The multivariable adjusted differences in serum INHB levels comparing the highest
      quartile of urinary MEHP to the lowest were - 18.29% (95% CI: - 31.89%, - 1.98%;
      P-trend = 0.04). Women in the second to fourth quartiles of MEOHP had a
      significant decrease of - 23.74% (95% CI: -35.85%, - 9.24%), - 19.91% (95% CI: 
      33.30%, - 3.82%) and - 20.23% (95% CI: -34.43%, - 2.96%), respectively, in INHB
      levels compared to the first quartile. In the spline analysis, we identified a
      nonlinear relationship between MEOHP exposure and serum INHB. CONCLUSIONS: We
      provided evidence for a negative association between urinary concentrations of
      certain phthalate metabolites and serum INHB levels, suggesting an adverse effect
      of phthalates exposure on growing antral follicles. Whether phthalates exposure
      at environmentally level will pose a risk for ovarian reserve needs further
      investigation.

PMID- 29471861
TI  - Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In
      Teenagers on the interNET in the NHS) compared to Activity Management to treat
      paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME):
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis
      (CFS/ME) is a relatively common and disabling condition. The National Institute
      for Health and Clinical Excellence (NICE) recommends Cognitive Behavioural
      Therapy (CBT) as a treatment option for paediatric CFS/ME because there is good
      evidence that it is effective. Despite this, most young people in the UK are
      unable to access local specialist CBT for CFS/ME. A randomised controlled trial
      (RCT) showed FITNET was effective in the Netherlands but we do not know if it is
      effective in the National Health Service (NHS) or if it is cost-effective. This
      trial will investigate whether FITNET-NHS is clinically effective and cost
      effective in the NHS. METHODS: Seven hundred and thirty-four paediatric patients
      (aged 11-17 years) with CFS/ ME will be randomised (1:1) to receive either FITNET
      NHS (online CBT) or Activity Management (delivered via video call). The internal
      pilot study will use integrated qualitative methods to examine the feasibility of
      recruitment and the acceptability of treatment. The full trial will assess
      whether FITNET-NHS is clinically effective and cost-effective. The primary
      outcome is disability at 6 months, measured using the SF-36-PFS (Physical
      Function Scale) questionnaire. Cost-effectiveness is measured via cost-utility
      analysis from an NHS perspective. Secondary subgroup analysis will investigate
      the effectiveness of FITNET-NHS in those with co-morbid mood disorders.
      DISCUSSION: If FITNET-NHS is found to be feasible and acceptable (internal pilot)
      and effective and cost-effective (full trial), its provision by the NHS has the
      potential to deliver substantial health gains for the large number of young
      people suffering from CFS/ME but unable to access treatment because there is no
      local specialist service. This trial will provide further evidence evaluating the
      delivery of online CBT to young people with chronic conditions. TRIAL
      REGISTRATION: ISRCTN registry, registration number: ISRCTN18020851 . Registered
      on 4 August 2016.

PMID- 29471862
TI  - Human-Forest interfaces in Hugumburda-Gratkhassu National Forest Priority Area,
      North-eastern Ethiopia.
AB  - BACKGROUND: Traditional management regimes and knowledge systems of forest
      resources have shaped forests throughout the world where materials from
      individual species are harvested in a sustainable manner. To comprehend this, the
      vegetation of Hugumburda-Gratkhassu Forest was described and related to
      anthropogenic factors. METHODS: Three ethnobotanical research methods were used
      to collect indigenous knowledge of the local inhabitants related to conservation
      and utilization of forest resources. Direct matrix ranking was conducted to
      discover local attitudes on species preference for multiple use. During this
      work, the 46 most important tree and shrub species were selected based on
      recommendations of local guides and key informants to determine the range of uses
      obtained from each species. Through paired comparison, activities supposed to be
      the major cause of degradation of the forest were adopted. Pairs of activities
      were then established from the relation n (n-1)/2. Each respondent was then asked
      to select an activity that he considered being a major problem to management of
      the forest. Semi-structured interviews were used to obtain information from sixty
      local informants to address community attitudes towards forest management and
      utilization. RESULTS: The result obtained from direct matrix ranking showed; that
      20 out of 46 plant species compared had the highest scores and rank, indicating
      that these species are the most important and are exploited by the local
      communities for multiple purposes. The paired comparison exercise revealed
      logging for construction materials to be the major threat to the forest due to
      cutting of large volume of wood for construction of churches, health centers,
      schools and new houses. Juniperus procera, Olea europaea ssp. cuspidata, Rhus
      glutinosa, Ficus sur, Hagenia abyssinica, Cassipourea malosana and Acacia etbaica
      were the most selected and exploited plant species for these purposes.
      CONCLUSIONS: Survival of protected areas depends on the support of local
      communities, rather than on fences, fines, or even force. The local communities
      in the study area have a rich indigenous ecological knowledge to suggest
      appropriate solutions for improvement of the forest resources. Thus the old
      tradition of isolating forests from the community has to be avoided and the basic
      needs and traditional rights of the communities over the uses of forest resources
      should be recognized.

PMID- 29471863
TI  - The microbiome in precision medicine: the way forward.
AB  - Novel associations between the human microbiome and health and disease are
      routinely emerging, and important host-microbiome interactions are targets for
      new diagnostics and therapeutics. Understanding how broadly host-microbe
      associations are maintained across populations is revealing individualized host
      microbiome phenotypes that can be integrated with other 'omics' data sets to
      enhance precision medicine.

PMID- 29471864
TI  - In tune with nature: Wolbachia does not prevent pre-copula acoustic communication
      in Aedes aegypti.
AB  - BACKGROUND: Mosquito-borne diseases are rapidly spreading to vast territories,
      putting at risk most of the world's population. A key player in this scenario is
      Aedes aegypti, a hematophagous species which hosts and transmits viruses causing
      dengue and other serious illnesses. Since vector control strategies relying only
      on insecticides have proven unsustainable, an alternative method involving the
      release of Wolbachia-harboring individuals has emerged. Its successful
      implementation vastly depends on how fit the released individuals are in the
      natural habitat, being able to mate with wild populations and to spread Wolbachia
      to subsequent generations. In mosquitoes, an important aspect of reproductive
      fitness is the acoustic communication between males and females, which translates
      to interactions between harmonic frequencies in close proximity flight. This
      study aimed to characterize the flight tone produced by individuals harboring
      Wolbachia, also evaluating their ability to establish stable acoustic
      interactions. METHODS: Wild-type (WT) and Wolbachia-harboring specimens (wMelBr)
      were thorax-tethered to blunt copper wires and placed at close proximity to
      sensitive microphones. Wing-beat frequencies (WBFs) were characterized at
      fundamental and harmonic levels, for both single individuals and couples.
      Harmonic interactions in homogeneous and heterogeneous couples of WT and wMelBr
      variants were identified, categorized and quantified accordingly. RESULTS: In
      tethered 'solo' flights, individuals harboring Wolbachia developed WBFs,
      differing slightly, in a sex-dependent way, from those of the WT strain. To test
      the ability to form harmonic 'duets', tethered couples of wMelBr and WT
      individuals were shuffled in different sex pairs and had their flight tones
      analyzed. All couple types, with WT and/or wMelBr individuals, were able to
      interact acoustically in the frequency range of 1300-1500 Hz, which translates to
      the convergence between male's second harmonic and female's third. No significant
      differences were found in the proportions of interacting couples between the pair
      types. Surprisingly, spectrograms also revealed the convergence between
      alternative harmonic frequencies, inside and outside the species putative hearing
      threshold. CONCLUSIONS: Wolbachia infection leads to small sex-dependent changes
      on the flight tones of Ae. aegypti, but it does not seem to prevent the
      stereotyped harmonic interaction between males and females. Therefore, when
      released in the natural habitat to breed with native individuals, Wolbachia
      harboring individuals shall be fit enough to meet the criteria of acoustically
      related mating behavior and promote bacteria dispersion effectively.

PMID- 29471865
TI  - A multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox
      eflornithine combination to standard eflornithine monotherapy for late stage
      Trypanosoma brucei gambiense human African trypanosomiasis in Uganda.
AB  - BACKGROUND: While the combination of nifurtimox and eflornithine (NECT) is
      currently recommended for the treatment of the late stage human African
      trypansomiasis (HAT), single-agent eflornithine was still the treatment of choice
      when this trial commenced. This study intended to provide supportive evidence to
      complement previous trials. METHODS: A multi-centre randomised, open-label, non
      inferiority trial was carried out in the Trypanosoma brucei gambiense endemic
      districts of North-Western Uganda to compare the efficacy and safety of NECT (200
      mg/kg eflornithine infusions every 12 h for 7 days and 8 hourly oral nifurtimox
      at 5 mg/kg for 10 days) to the standard eflornithine regimen (6 hourly at 100
      mg/kg for 14 days). The primary endpoint was the cure rate, determined as the
      proportion of patients alive and without laboratory signs of infection at 18
      months post-treatment, with no demonstrated trypanosomes in the cerebrospinal
      fluid (CSF), blood or lymph node aspirates, and CSF white blood cell count < 20
      /MUl. The non-inferiority margin was set at 10%. RESULTS: One hundred and nine
      patients were enrolled; all contributed to the intent-to-treat (ITT), modified
      intent-to-treat (mITT) and safety populations, while 105 constituted the per
      protocol population (PP). The cure rate was 90.9% for NECT and 88.9% for
      eflornithine in the ITT and mITT populations; the same was 90.6 and 88.5%,
      respectively in the PP population. Non-inferiority was demonstrated for NECT in
      all populations: differences in cure rates were 0.02 (95% CI: -0.07-0.11) and
      0.02 (95% CI: -0.08-0.12) respectively. Two patients died while on treatment (1
      in each arm), and 3 more during follow-up in the NECT arm. No difference was
      found between the two arms for the secondary efficacy and safety parameters. A
      meta-analysis involving several studies demonstrated non-inferiority of NECT to
      eflornithine monotherapy. CONCLUSIONS: These results confirm findings of earlier
      trials and support implementation of NECT as first-line treatment for late stage
      T. b. gambiense HAT. The overall risk difference for cure between NECT and
      eflornithine between this and two previous randomised controlled trials is 0.03
      (95% CI: -0.02-0.08). The NECT regimen is simpler, safer, shorter and less
      expensive than single-agent DFMO. TRIAL REGISTRATION: ISRCTN ISRCTN03148609
      (registered 18 April 2008).

PMID- 29471866
TI  - Endophenotypes in psychiatric disease: prospects and challenges.
AB  - Endophenotypes, quantitative neurobehavioral traits that index genetic
      susceptibility for a psychiatric disorder, have been examined in thousands of
      studies. Nevertheless, they have underexploited potential to provide etiological
      insights into prognosis, how psychopathology develops, the etiology of
      comorbidity, and the mechanisms of gene function.

PMID- 29471867
TI  - Earplugs in the ICU: To sleep, to dream.

PMID- 29471868
TI  - Asymptomatic thyroiditis presenting as pyrexia of unknown origin: a case report.
AB  - BACKGROUND: Pyrexia of unknown origin is a difficult and challenging problem for
      the physician. Endocrine disorders, such as subacute thyroiditis, rarely present
      with pyrexia of unknown origin. Subacute thyroiditis can have a broad spectrum of
      clinical presentations including fever and biochemical thyrotoxicosis without
      overt signs or symptoms. CASE PRESENTATION: A previously healthy 42-year-old Sri
      Lankan Sinhalese man was extensively investigated for a prolonged fever of 3
      weeks with high inflammatory markers. He had mild tenderness over his neck with
      cervical lymphadenopathy with no thyrotoxic symptoms or signs. An ultrasound scan
      revealed an enlarged thyroid with increased vascularity and he had suppressed
      thyroid-stimulating hormone with elevated free thyroxine and free
      triiodothyronine hormone levels. Fine-needle aspiration cytology confirmed
      thyroiditis. He responded well to low-dose steroids. CONCLUSION: Subacute
      thyroiditis should be considered in the diagnostic workup of pyrexia of unknown
      origin even in the absence of overt toxic symptoms of thyroid hormone excess.

PMID- 29471870
TI  - Autologous bone marrow-derived mononuclear cell therapy in Chinese patients with
      critical limb ischemia due to thromboangiitis obliterans: 10-year results.
AB  - BACKGROUND: For patients with thromboangiitis obliterans (TAO), revascularization
      with bypass or angioplasty is frequently not feasible due to the poor outflow of
      the distal small vessels. We evaluated the long-term results of our experience
      treating patients with TAO with autologous bone marrow-derived mononuclear cells
      (ABMMNCs) to determine the safety and efficacy of ABMMNC therapy in patients with
      critical limb ischemia due to TAO. METHODS: This was a retrospective chart review
      from a single university hospital vascular surgery center between January 2005
      and July 2006. Patients were treated with smoking cessation and either aspirin
      (100 mg/day) alone or aspirin and ABMMNC injection according to patient
      preference. Groups were compared for demographics, clinical characteristics, and
      short-term and long-term results. RESULTS: Of 59 patients with TAO who were
      treated, 19 patients elected aspirin alone and 40 patients elected aspirin and
      ABMMNC injection. No patients suffered perioperative complications and 49 (83%)
      patients remained smoke-free for 10 years. The 10-year amputation-free survival
      was 85.3% (29/34) in patients treated with ABMMNCs compared to 40% (6/15) in
      patients treated with aspirin alone (p = 0.0019). Ulcer area (p < 0.0001), toe
      brachial index (TBI; p < 0.0001), transcutaneous oxygen pressure (TcPO2; p <
      0.0001), and pain score (p < 0.0001) were also significantly improved with ABMMNC
      treatment, although there was no difference in mean ankle-brachial index (ABI; p
      = 0.806). CONCLUSIONS: In patients with critical limb ischemia due to TAO, ABMMNC
      treatment was safe and effective. ABMMNC treatment significantly improved
      amputation-free survival, ulcer healing, and pain, although there is no
      difference in ABI compared to treatment with aspirin alone.

PMID- 29471871
TI  - Correction: Sudden death associated with silent myocardial infarction in a 35
      year-old man: a case report.
AB  - In the publication of this article [1], there is an error in Table 1 at the Test
      Ca2+ at the Result. The error in Test Ca2+ Result: '1.24' Should instead read
      Test Ca2+ Result: '2.24' This has now been included in this erratum.

PMID- 29471869
TI  - Type 2 diabetes impairs odour detection, olfactory memory and olfactory
      neuroplasticity; effects partly reversed by the DPP-4 inhibitor Linagliptin.
AB  - Recent data suggest that olfactory deficits could represent an early marker and a
      pathogenic mechanism at the basis of cognitive decline in type 2 diabetes (T2D).
      However, research is needed to further characterize olfactory deficits in
      diabetes, their relation to cognitive decline and underlying mechanisms.The aim
      of this study was to determine whether T2D impairs odour detection, olfactory
      memory as well as neuroplasticity in two major brain areas responsible for
      olfaction and odour coding: the main olfactory bulb (MOB) and the piriform cortex
      (PC), respectively. Dipeptidyl peptidase-4 inhibitors (DPP-4i) are clinically
      used T2D drugs exerting also beneficial effects in the brain. Therefore, we aimed
      to determine whether DPP-4i could reverse the potentially detrimental effects of
      T2D on the olfactory system.Non-diabetic Wistar and T2D Goto-Kakizaki rats,
      untreated or treated for 16 weeks with the DPP-4i linagliptin, were employed.
      Odour detection and olfactory memory were assessed by using the block, the
      habituation-dishabituation and the buried pellet tests. We assessed
      neuroplasticity in the MOB by quantifying adult neurogenesis and GABAergic
      inhibitory interneurons positive for calbindin, parvalbumin and carletinin. In
      the PC, neuroplasticity was assessed by quantifying the same populations of
      interneurons and a newly identified form of olfactory neuroplasticity mediated by
      post-mitotic doublecortin (DCX) + immature neurons.We show that T2D dramatically
      reduced odour detection and olfactory memory. Moreover, T2D decreased
      neurogenesis in the MOB, impaired the differentiation of DCX+ immature neurons in
      the PC and altered GABAergic interneurons protein expression in both olfactory
      areas. DPP-4i did not improve odour detection and olfactory memory. However, it
      normalized T2D-induced effects on neuroplasticity.The results provide new
      knowledge on the detrimental effects of T2D on the olfactory system. This
      knowledge could constitute essentials for understanding the interplay between T2D
      and cognitive decline and for designing effective preventive therapies.

PMID- 29471873
TI  - miRCancerdb: a database for correlation analysis between microRNA and gene
      expression in cancer.
AB  - OBJECTIVES: microRNAs regulate expression of target genes by specifically binding
      to their transcripts, subsequently leading to translational inhibition or mRNA
      degradation. Gene regulation by microRNAs has been implicated in a wide range of
      physiological and pathological conditions. Here, we leverage the use of public
      access data and the available genomic annotations to pre-calculate the
      correlation of the expression of a large number of microRNAs with gene at the
      mRNA and protein level in the context of cancers. RESULTS: Expression data of
      miRNAs, mRNAs and proteins in cancer patients from The Cancer Genome Atlas along
      with TargetScan miRNAs-target annotations were used to calculate the expression
      correlations between miRNAs and features (mRNAs/proteins) in a number of cancer
      studies. We then packed the output of this analysis into a database and made it
      available through an interactive web application. The miRCancerdb is an easy-to
      use database to investigate the microRNAs-dependent regulation of target genes
      involved in development of cancer.

PMID- 29471872
TI  - A reservoir of 'historical' antibiotic resistance genes in remote pristine
      Antarctic soils.
AB  - BACKGROUND: Soil bacteria naturally produce antibiotics as a competitive
      mechanism, with a concomitant evolution, and exchange by horizontal gene
      transfer, of a range of antibiotic resistance mechanisms. Surveys of bacterial
      resistance elements in edaphic systems have originated primarily from human
      impacted environments, with relatively little information from remote and
      pristine environments, where the resistome may comprise the ancestral gene
      diversity. METHODS: We used shotgun metagenomics to assess antibiotic resistance
      gene (ARG) distribution in 17 pristine and remote Antarctic surface soils within
      the undisturbed Mackay Glacier region. We also interrogated the phylogenetic
      placement of ARGs compared to environmental ARG sequences and tested for the
      presence of horizontal gene transfer elements flanking ARGs. RESULTS: In total,
      177 naturally occurring ARGs were identified, most of which encoded single or
      multi-drug efflux pumps. Resistance mechanisms for the inactivation of
      aminoglycosides, chloramphenicol and beta-lactam antibiotics were also common.
      Gram-negative bacteria harboured most ARGs (71%), with fewer genes from Gram
      positive Actinobacteria and Bacilli (Firmicutes) (9%), reflecting the taxonomic
      composition of the soils. Strikingly, the abundance of ARGs per sample had a
      strong, negative correlation with species richness (r = - 0.49, P < 0.05). This
      result, coupled with a lack of mobile genetic elements flanking ARGs, suggests
      that these genes are ancient acquisitions of horizontal transfer events.
      CONCLUSIONS: ARGs in these remote and uncontaminated soils most likely represent
      functional efficient historical genes that have since been vertically inherited
      over generations. The historical ARGs in these pristine environments carry a
      strong phylogenetic signal and form a monophyletic group relative to ARGs from
      other similar environments.

PMID- 29471874
TI  - Calcitonin gene-related peptide (receptor) antibodies: an exciting avenue for
      migraine treatment.
AB  - Specific prophylactic migraine treatments are urgently needed because of the
      unmet needs of many migraine patients. Antibodies targeting calcitonin gene
      related peptide (CGRP) or its receptor have recently shown efficacy in episodic
      and chronic migraine and will be available soon.

PMID- 29471875
TI  - Pre-treatment DWI as a predictor of overall survival in locally advanced
      pancreatic cancer treated with Cyberknife radiotherapy and sequential S-1
      therapy.
AB  - BACKGROUND: To identify the value of the pre-treatment apparent diffusion
      coefficient (ADC) derived from diffusion weighted imaging (DWI) in predicting the
      overall survival (OS) for locally advanced pancreatic cancer (LAPC) treated with
      Cyberknife followed by sequential S-1 chemotherapy. METHODS: Patients with UICC
      T4 LAPC who underwent DWI scan (3.0 Tesla) using two b-values (0, 600 s/mm2) in
      our center between 2015 and 2017 were enrolled. Mean ADCs of the region of
      interest (ROI) drawn manually on DWI imaging were measured by two independent
      radiologists at an interval of 1 month. The association between prognostic
      factors and patient survival was determined using univariate and multivariate
      analyses. Cox proportional hazard model was used for identification of
      independent prognostic factors of OS. RESULTS: A total of 41 patients (28 males
      and 13 females) were included, with a median age of 64 years, with 5 patients (3
      males and 2 females) lost. The median OS was 11.7 months (range 2.8-23.3) among
      all 41 patients. The 1-year OS was 46% (95% CI 30%-62%). Univariate and
      multivariate analyses indicated that pre-treatment ADC value (HR 10.652, P =
      0.0093), age (HR 0.952, P = 0.015), CA19-9 (HR 1.001, P = 0.0022) and
      administration of S-1 (HR 0.128, P = 0.0002) were independent predicting factors
      of OS. CONCLUSION: The mean ADC value of the primary tumor on pre-treatment DWI
      imaging was an independent predictor of OS in patients with LAPC receiving
      Cyberknife followed by sequential S-1.

PMID- 29471876
TI  - Effect of propranolol on heart rate variability in hyperthyroidism.
AB  - OBJECTIVES: We aimed to determine the effect of propanolol on heart rate
      variability (HRV) in hyperthyroidism before antithyroid treatment. This was a
      before and after study, on ten patients presenting overt hyperthyroidism naive to
      treatment. In each patient, a resting electrocardiogram was done followed by
      estimation of cardiac autonomic dysfunction during five maneuvers (Ewing battery
      tests). Long term HRV measurement was done using 24 h ambulatory
      electrocardiographic recording. This automatically provided estimation of HRV
      using SDNN and RMSSD index, LF, HF, and HF/LF ratio. After baseline
      investigations, 40 mg of propanolol was given twice a day for 3 days and same
      parameters were measured after 72 h of treatment. RESULTS: Our patients were aged
      40 +/- 10 years. Propanolol significantly reduced RR and HR interval (669 ms vs
      763 ms and 91 vs 79 bpm; p < 0.01). QT and PR space were significantly extended
      (360 vs 384 ms and 133 vs 172 ms; p = 0.01). It increases QRS complex and blood
      pressure response to sustained handgrip but failed to modify previously decreased
      heart response to deep breathing. HRV parameters such as SDNN, RMSSD, LF, HF and
      sympathovagal balance estimate by HF/LF ratio remained unchanged. Although a
      significant reduction in heart excitability, propanolol failed to restore a good
      sympathovagal balance in hyperthyroidism. Trial registration NCT03393728
      "Retrospectively registered".

PMID- 29471877
TI  - A personalized intervention to prevent depression in primary care: cost
      effectiveness study nested into a clustered randomized trial.
AB  - BACKGROUND: Depression is viewed as a major and increasing public health issue,
      as it causes high distress in the people experiencing it and considerable
      financial costs to society. Efforts are being made to reduce this burden by
      preventing depression. A critical component of this strategy is the ability to
      assess the individual level and profile of risk for the development of major
      depression. This paper presents the cost-effectiveness of a personalized
      intervention based on the risk of developing depression carried out in primary
      care, compared with usual care. METHODS: Cost-effectiveness analyses are nested
      within a multicentre, clustered, randomized controlled trial of a personalized
      intervention to prevent depression. The study was carried out in 70 primary care
      centres from seven cities in Spain. Two general practitioners (GPs) were randomly
      sampled from those prepared to participate in each centre (i.e. 140 GPs), and
      3326 participants consented and were eligible to participate. The intervention
      included the GP communicating to the patient his/her individual risk for
      depression and personal risk factors and the construction by both GPs and
      patients of a psychosocial programme tailored to prevent depression. In addition,
      GPs carried out measures to activate and empower the patients, who also received
      a leaflet about preventing depression. GPs were trained in a 10- to 15-h
      workshop. Costs were measured from a societal and National Health care
      perspective. Qualityadjustedlife years were assessed using the EuroQOL five
      dimensions questionnaire. The time horizon was 18 months. RESULTS: With a
      willingness-to-pay threshold of ?10,000 (L8568) the probability of cost
      effectiveness oscillated from 83% (societal perspective) to 89% (health
      perspective). If the threshold was increased to ?30,000 (L25,704), the
      probability of being considered cost-effective was 94% (societal perspective) and
      96%, respectively (health perspective). The sensitivity analysis confirmed these
      results. CONCLUSIONS: Compared with usual care, an intervention based on personal
      predictors of risk of depression implemented by GPs is a cost-effective strategy
      to prevent depression. This type of personalized intervention in primary care
      should be further developed and evaluated. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT01151982. Registered on June 29, 2010.

PMID- 29471878
TI  - Objective assessment of physical activity and sedentary behaviour in knee
      osteoarthritis patients - beyond daily steps and total sedentary time.
AB  - BACKGROUND: Knee osteoarthritis patients may become physically inactive due to
      pain and functional limitations. Whether physical activity exerts a protective or
      harmful effect depends on the frequency, intensity, time and type (F.I.T.T.). The
      F.I.T.T. dimensions should therefore be assessed during daily life, which so far
      has hardly been feasible. Furthermore, physical activity should be assessed
      within subgroups of patients, as they might experience different activity
      limitations. Therefore, this study aimed to objectively describe physical
      activity, by assessing the F.I.T.T. dimensions, and sedentary behaviour of knee
      osteoarthritis patients during daily life. An additional goal was to determine
      whether activity events, based on different types and durations of physical
      activity, were able to discriminate between subgroups of KOA patients based on
      risk factors. METHODS: Clinically diagnosed knee osteoarthritis patients
      (according to American College of Rheumatology criteria) were monitored for 1
      week with a tri-axial accelerometer. Furthermore, they performed three functional
      tests and completed the Knee Osteoarthritis Outcome Score. Physical activity
      levels were described for knee osteoarthritis patients and compared between
      subgroups. RESULTS: Sixty-one patients performed 7303 mean level steps, 319
      ascending and 312 descending steps and 601 bicycle crank revolutions per day.
      Most waking hours were spent sedentary (61%), with 4.6 bouts of long duration (>
      30 min). Specific events, particularly ascending and descending stairs/slopes,
      brief walking and sedentary bouts and prolonged walking bouts, varied between
      subgroups. CONCLUSIONS: From this sample of KOA patients, the most common form of
      activity was level walking, although cycling and stair climbing activities
      occurred frequently, highlighting the relevance of distinguishing between these
      types of PA. The total active time encompassed a small portion of their waking
      hours, as they spent most of their time sedentary, which was exacerbated by
      frequently occurring prolonged bouts. In this study, event-based parameters, such
      as stair climbing or short bouts of walking or sedentary time, were found more
      capable of discriminating between subgroups of KOA patients compared to overall
      levels of PA and sedentary time. Thereby, subtle limitations in physical
      behaviour of KOA-subgroups were revealed, which might ultimately be targeted in
      rehabilitation programs. TRIAL REGISTRATION: German Clinical Trials Registry
      under ' DRKS00008735 ' at 02.12.2015.

PMID- 29471879
TI  - Dosimetric impact of tumor treating field (TTField) transducer arrays onto
      treatment plans for glioblastomas - a planning study.
AB  - BACKGROUND: Tumor-Treating Fields (TTFields) are a novel treatment strategy for
      glioblastoma (GBM) that is approved for the use concomitantly to adjuvant
      chemotherapy. Preclinical data suggest a synergistic interaction of TTFields and
      radiotherapy (RT). However, the dosimetric uncertainties caused by the highly
      dense arrays have led to caution of applying the TTF setup during RT. METHODS: In
      a RW3 slab phantom we compared the MV- and kV-CT based planned dose with the
      measured dose. VMAT-plans were optimized on MV-CTs of an Alderson head phantom
      without TTF arrays and then re-calculated on the same phantom equipped with TTF
      arrays. Dose at organs at risk (OAR) and target volumes (PTVs) were compared.
      RESULTS: Measurements at a depth of 2, 3 and 4 cm of a RW 3 slab phantom show an
      attenuation due to TTField arrays of 3.4, 3.7 and 2.7% respectively. This was in
      line with calculated attenuations based on MV-CT (1.2, 2.5 and 2.5%) but not with
      the attenuation expected from kV-CT based calculations (7.1, 8.2 and 8.6%).
      Consecutive MV-CT based VMAT planning and re-calculation reveals, that the
      conformity and homogeneity are not affected by the presence of TTField arrays.
      The dose at organs at risk (OAR) can show increases or decreases by < 0.5 Gy,
      which should be considered especially in cases next to the scull base.
      CONCLUSION: MV-CT based dose calculation results in reliable dose distributions
      also in the presence of TTField arrays. There is a small but clinically not
      relevant interaction between the TTField arrays and VMAT dose application. Thus,
      daily replacement of TTField arrays is not necessary in regard to deeply located
      OARs. RT is feasible, when a VMAT treatment plan is optimized to an array free
      planning CT. As the biologic effect of a concomitant treatment especially on OARs
      is currently unknown, a concomitant treatment should be performed only within
      clinical trials.

PMID- 29471880
TI  - [18F]FSPG-PET reveals increased cystine/glutamate antiporter (xc-) activity in a
      mouse model of multiple sclerosis.
AB  - BACKGROUND: The cystine/glutamate antiporter (xc-) has been implicated in several
      neurological disorders and, specifically, in multiple sclerosis (MS) as a
      mediator of glutamate excitotoxicity and proinflammatory immune responses. We
      aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer,
      (4S)-4-(3-[18F]fluoropropyl)-L-glutamate ([18F]FSPG), for its ability to allow
      non-invasive monitoring of xc- activity in a mouse model of MS. METHODS:
      Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by
      subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG35-55) peptide
      in complete Freund's adjuvant (CFA) followed by pertussis toxin. Control mice
      received CFA emulsion and pertussis toxin without MOG peptide, while a separate
      cohort of naive mice received no treatment. PET studies were performed to
      investigate the kinetics and distribution of [18F]FSPG in naive, control, pre
      symptomatic, and symptomatic EAE mice, compared to 18F-fluorodeoxyglucose
      ([18F]FDG). After final PET scans, each mouse was perfused and radioactivity in
      dissected tissues was measured using a gamma counter. Central nervous system
      (CNS) tissues were further analyzed using ex vivo autoradiography or western
      blot. [18F]FSPG uptake in human monocytes, and T cells pre- and post-activation
      was investigated in vitro. RESULTS: [18F]FSPG was found to be more sensitive than
      [18F]FDG at detecting pathological changes in the spinal cord and brain of EAE
      mice. Even before clinical signs of disease, a small but significant increase in
      [18F]FSPG signal was observed in the spinal cord of EAE mice compared to
      controls. This increase in PET signal became more pronounced in symptomatic EAE
      mice and was confirmed by ex vivo biodistribution and autoradiography. Likewise,
      in the brain of symptomatic EAE mice, [18F]FSPG uptake was significantly higher
      than controls, with the largest changes observed in the cerebellum. Western blot
      analyses of CNS tissues revealed a significant correlation between light chain of
      xc- (xCT) protein levels, the subunit of xc- credited with its transporter
      activity, and [18F]FSPG-PET signal. In vitro [18F]FSPG uptake studies suggest
      that both activated monocytes and T cells contribute to the observed in vivo PET
      signal. CONCLUSION: These data highlight the promise of [18F]FSPG-PET as a
      technique to provide insights into neuroimmune interactions in MS and the in vivo
      role of xc- in the development and progression of this disease, thus warranting
      further investigation.

PMID- 29471881
TI  - Evaluation of the long-term efficacy of K-Othrine(r) PolyZone on three surfaces
      against laboratory reared Anopheles gambiae in semi-field conditions.
AB  - BACKGROUND: In this semi-field study, a new polymer-enhanced deltamethrin
      formulation, K-Othrine(r) PolyZone, was compared to a standard deltamethrin
      product for residual activity against a susceptible strain of laboratory-reared
      Anopheles gambiae using standard WHO cone bioassays. METHODS: Residual
      insecticide efficacy was recorded after exposure to metal, cement and wood panels
      maintained in experimental huts in sub-tropical environmental conditions in north
      central Florida, USA, and panels stored in a climate controlled chamber located
      at the Centers for Disease Control and Prevention, Georgia, USA. CONCLUSIONS: K
      Othrine(r) PolyZone demonstrated 100% control on metal and cement panels 1 year
      post application and > 80% control on wood panels up to 6 mo. The new formulation
      should be considered for use in indoor residual spray programmes requiring long
      term control of malaria vectors.

PMID- 29471882
TI  - The use of Latin terminology in medical case reports: quantitative, structural,
      and thematic analysis.
AB  - BACKGROUND: This paper focuses on the prevalence of Latin terms and
      terminological collocations in the issues of Journal of Medical Case Reports
      (February 2007-August 2017) and discusses the role of Latin terminology in the
      contemporary process of writing medical case reports. METHODS: The objective of
      the research is to study the frequency of using Latin terminology in English
      language medical case reports, thus providing relevant guidelines for medical
      professionals who deal with this genre and drawing their attention to the
      peculiarities of using Latin in case reports. The selected medical case reports
      are considered, using methods of quantitative examination and structural,
      narrative, and contextual analyses. RESULTS: We developed structural and thematic
      typologies of Latin terms and expressions, and we conducted a quantitative
      analysis that enabled us to observe the tendencies in using these lexical units
      in medical case reports. The research revealed that the use of Latin fully
      complies with the communicative strategies of medical case reports as a genre.
      Owing to the fact that Latin medical lexis is internationally adopted and
      understood worldwide, it promotes the conciseness of medical case reports, as
      well as contributes to their narrative style and educational intentions.
      CONCLUSIONS: The adequate use of Latin terms in medical case reports is an
      essential prerequisite of effective sharing of one's clinical findings with
      fellow researchers from all over the world. Therefore, it is highly important to
      draw students' attention to Latin terms and expressions that are used in medical
      case reports most frequently. Hence, the analysis of structural, thematic, and
      contextual features of Latin terms in case reports should be an integral part of
      curricula at medical universities.

PMID- 29471883
TI  - The extremity localized classic osteosarcomas have better survival than the axial
      non-classics.
AB  - BACKGROUND: Osteosarcoma is one of the most malignant primary bone cancers, while
      is rarely reported in China. Of note, very few data of prognosis has been
      documented in this region. Thus, we carried a retrospective study to identify
      prognostic factors and to analyze outcomes in patients of both classic and non
      classic high-grade osteosarcomas. Classic osteosarcoma is defined as of high
      grade histology, age below 40 years, with extremity localized primary tumor, and
      without detectable metastasis at primary diagnosis. METHODS: A total of 98
      patients (68 classic and 30 non-classic) aged from 4 to 64 years old were
      diagnosed as high-grade osteosarcoma from 2008 to 2015 in Nanfang Hospital,
      Guangzhou, China. Univariate and multivariate analyses were performed to identify
      the independent predictors for overall survival and event-free survival. Kaplan
      Meier method was used for survival analysis. RESULTS: The median overall survival
      was 117 vs. 21 months, and the median event-free survival was 31 vs. 6 months in
      classic and non-classic osteosarcoma, respectively. The most frequently found
      tumor site was around the knee. The classic osteosarcoma had better overall
      survival and event-free survival than the non-classics. Tumor site and primary
      metastasis were found to be associated with overall survival and event-free
      survival in the univariate analysis. In the multivariate Cox regression analysis,
      tumor site and primary metastasis were each verified as independent prognostic
      factors. However, no similar result was found in elevated serum alkaline
      phosphatase or lactate dehydrogenase. Amputation or limb salvage surgery had no
      significant effect on overall survival and event-free survival in the extremity
      osteosarcomas. Classic osteosarcomas with extremity tumor site and free of
      primary metastasis exhibited better overall survival and event-free survival,
      while the axial and metastatic non-classics exhibited the worse. CONCLUSIONS: The
      extremity classic osteosarcomas have better survivals than the axial non-classic
      cases. Amputation and limb salvage surgery make no significant change in overall
      survival and event-free survival in the extremity osteosarcomas. TRIAL
      REGISTRATION: Nanfang2013071; Date of registration: 7 September 2013
      (retrospectively registered).

PMID- 29471884
TI  - Should we measure the central venous pressure to guide fluid management? Ten
      answers to 10 questions.
AB  - The central venous pressure (CVP) is the most frequently used variable to guide
      fluid resuscitation in critically ill patients, although its use has been
      challenged. In this viewpoint, we use a question and answer format to highlight
      the potential advantages and limitations of using CVP measurements to guide fluid
      resuscitation.

PMID- 29471886
TI  - LncRNA NORAD contributes to colorectal cancer progression by inhibition of miR
      202-5p.
AB  - Previous study indicates that long noncoding RNA NORAD could serve as a competing
      endogenous RNA to pancreatic cancer metastasis. However, its role in colorectal
      cancer requires to be investigated. In the present study, we found that the
      expression of NORAD was significantly upregulated in colorectal cancer (CRC)
      tissues. Furthermore, the expression of NORAD was positively related with CRC
      metastasis and patients' poor prognosis. Knockdown of NORAD markedly inhibited
      CRC cell proliferation, migration and invasion but induced cell apoptosis in
      vitro. In vivo experiments also indicated an inhibitory effect of NORAD on tumor
      growth. In mechanism, we found that NORAD served as a competing endogenous RNA
      for miR-202-5p. We found that there was an inversely relationship between the
      expression of NORAD and miR-202-5p in CRC tissues. Moreover, overexpression of
      miR-202-5p in SW480 and HCT116 cells significantly inhibited cellular
      proliferation, migration and invasion. Taken together, our study demonstrated
      NORAD/miR-202-5p axis plays a pivot function on CRC progression.

PMID- 29471887
TI  - Long non-coding RNA CCAL promotes papillary thyroid cancer progression by
      activation of NOTCH1 pathway.
AB  - Long non-coding RNA CCAL has been reported to promote tumor progression in
      various human cancers, including hepatocellular carcinoma, osteosarcoma, and
      colorectal cancer. However, the role of CCAL in papillary thyroid cancer remains
      largely unknown. In the present study, we found that the expression of CCAL was
      upregulated in papillary thyroid tumor tissues compared to adjacent normal
      tissues. Moreover, the expression of CCAL was positively related with papillary
      thyroid cancer severity and TNM stage, and predicated poor prognosis. Besides, we
      found that knockdown of CCAL significantly inhibited papillary thyroid cancer
      cell proliferation, migration and invasion in vitro and reduced tumor growth and
      metastasis in vivo. In mechanism, we found that knockdown of CCAL dramatically
      decreased the expression of NOTCH1 and suppressed the activation of NOTCH1
      signaling pathway. Furthermore, Overexpression of NOTCH1 rescued the
      proliferation, migration and invasion in papillary thyroid cancer cells. Taken
      together, our data indicated that CCAL promoted papillary thyroid cancer
      development and progression by activation of NOTCH1 pathway, which provided a new
      insight on the design of therapeutic targets.

PMID- 29471885
TI  - Does bird metabolic rate influence mosquito feeding preference?
AB  - BACKGROUND: Host selection by mosquitoes plays a central role in the transmission
      of vector-borne infectious diseases. Although interspecific variation in mosquito
      attraction has often been reported, the mechanisms underlying intraspecific
      differences in hosts' attractiveness to mosquitoes are still poorly known.
      Metabolic rate is related to several physiological parameters used as location
      cues by mosquitoes, and so potentially affect host-vector contact rates.
      Therefore, individual hosts with higher metabolic rates should be more attractive
      to host-seeking mosquitoes. Here, we experimentally investigated the role of bird
      metabolic rate in the feeding preferences of Culex pipiens (Linnaeus), a
      widespread mosquito vector of many pathogens affecting human and wildlife health.
      RESULTS: Passer domesticus (Linnaeus) pairs containing one bird treated with 2,4
      dinitrophenol (DNP) and the other injected with phosphate-buffered saline
      solution (PBS) (i.e. control) were simultaneously exposed overnight to
      mosquitoes. The treatment did not affect the proportion of mosquitoes biting on
      each individual. However, mosquito feeding preference was negatively associated
      with bird resting metabolic rate but positively with bird body mass. These two
      variables explained up to 62.76% of the variations in mosquito feeding
      preference. CONCLUSIONS: The relationships between mosquito feeding preferences
      and individual host characteristics could be explained by enhanced anti-mosquito
      behaviour associated with higher metabolic rates. The potential role of cues
      emitted by hosts is also discussed. Thus, individuals with high metabolism may
      actively avoid being bitten by mosquitoes, despite releasing more attractant
      cues. Since metabolic rates can be related to individual differences in
      personality and life history traits, differences in mosquitoes' feeding
      preferences may be related to intraspecific differences in exposure to vector
      borne pathogens.

PMID- 29471888
TI  - Liquiritigenin inhibits colorectal cancer proliferation, invasion and epithelial
      to mesenchymal transition by decreasing expression of runt-related transcription
      factor 2.
AB  - Inhibition of tumor metastasis is one of the most important purposes in
      colorectal cancer (CRC) treatment. This study aimed to explore the effects of
      liquiritigenin, one of flavonoids extracted from the roots of Glycyrrhiza
      uralensis Fisch, on HCT116 cell proliferation, invasion, and epithelial to
      mesenchymal transition (EMT). We found that liquiritigenin significantly
      inhibited HCT116 cell proliferation, invasion and EMT process but had no
      influence on cell apoptosis. Moreover, liquiritigenin remarkably reduced the
      expression of runt-related transcription factor 2 (Runx2) in HCT116 cells.
      Overexpression of Runx2 obviously reversed the liquiritigenin-induced invasion
      and EMT inhibition. Furthermore, liquiritigenin inactivated the phosphoinositide
      3-kinase/protein kinase B (PI3K/AKT) pathway in HCT116 cells. Up-regulation of
      Runx2 reversed the liquiritigenin-induced PI3K/AKT pathway inactivation. In
      conclusion, our research verified that liquiritigenin exerted significant
      inhibitory effects on CRC invasion and EMT process by down-regulating the
      expression of Runx2 and inactivating PI3K/AKT signaling pathway. Liquiritigenin
      could be as an effective therapeutic and prevention medicine for CRC treatment.

PMID- 29471889
TI  - MiR-365 suppresses cholangiocarcinoma cell proliferation and induces apoptosis by
      targeting E2F2.
AB  - Cholangiocarcinoma (CCA) is one of the most malignant adenocarcinoma arising from
      bile duct epithelial cells. However,the molecular mechanism regulating CCA
      development and progression requires to be investigated. Here, we found that miR
      365 was downregulated in CCA tissues compared with adjacent normal tissues. By
      functional experiments, we found that overexpression of miR-365 significantly
      inhibited CCA cell proliferation and promoted cellular apoptosis in vitro.
      Furthermore, administration with miR-365 markedly suppressed the growth of tumor
      tissues in vivo. Mechanistically, we identified E2F2 was the target gene of miR
      365 in CCA cells. We found that overexpression significantly inhibited the
      expression of E2F2 in CCA cells. And there was an inversely correlation between
      the expression levels of E2F2 and miR-365 in CCAtissues. What's more, we found
      that E2F2 was highly expressed in CCA tissues and cell lines. And restoration of
      E2F2 in miR-365-overexpressing CCA cells promoted cell viability and reduced
      cellular apoptosis in CCA. Collectively, our study demonstrated the essential
      role of miR-365 and its functional mechanism in CCA cells, which provided a new
      insight on the design of therapeutic targets for CCA treatment.

PMID- 29471890
TI  - MicroRNA-744 inhibits cellular proliferation and invasion of colorectal cancer by
      directly targeting oncogene Notch1.
AB  - Accumulated studies have strongly implicated aberrantly expressed microRNAs
      (miRNAs) in carcinogenesis and cancer progression of various cancers, including
      colorectal cancer (CRC). Hence, a comprehensive study of miRNAs and their
      association with CRC may be a promising therapeutic method for patients with this
      malignancy. MiRNA-744 (miR-744) is abnormally expressed in several types of human
      cancer. Thus far, little is known about the expression, biological roles and
      exact mechanisms of miR-744 in CRC. Thus, the present study measured the
      expression level of miR-744 and investigated its roles and associated molecular
      mechanisms in CRC. This study demonstrated that miR-744 expression was
      significantly underexpressed in CRC tissues and cell lines. Low miR-744
      expression was positively associated with lymphatic metastasis and TNM stage.
      Functional experiments revealed that miR-744 overexpression obviously inhibited
      the proliferation and invasion of CRC cells. Furthermore, Notch1 was identified
      as a direct target of miR-744 in CRC. Moreover, the inhibition of Notch1
      phenocopied the inhibitory effects of miR-744 overexpression on CRC cells.
      Restored Notch1 expression markedly rescued the tumour suppressive effects of miR
      744 overexpression on CRC cells. Overall, miR-744 exhibits an essential role in
      CRC progression, and the miR-744/Notch1 axis may provide novel insights into
      future treatments for patients with CRC.

PMID- 29471891
TI  - MiR-188-5p suppresses gastric cancer cell proliferation and invasion via
      targeting ZFP91.
AB  - MicroRNAs (miRNAs) have been demonstrated to be essential regulators in the
      development and progression of various cancers. The role of miR-188-5p in gastric
      cancer has not been determined. In this study, we found that the expression of
      miR-188-5p was downregulated in gastric cancer (GC) tissues compared with
      adjacent normal tissues. And lowly expressed miR-188-5p was significantly
      associated with lymph node metastasis and advanced TNM stage. Moreover,
      overexpression of miR-188-5p significantly inhibited GC cell proliferation,
      migration and invasion but promoted cellular apoptosis. In mechanism, we
      identified transcription factor ZFP91 as a target gene of miR-188-5p in GC. We
      found that miR-188-5p overexpression significantly inhibited the expression of
      ZFP91 in GC cell lines. And there was an inversely correlation between the
      expression of miR-188-5p and ZFP91 in GC tissues. What's more, we found that
      restoration of ZFP91 in miR-188-5poverexpressed MGC-803 and SGC-7901 cells
      promoted cell proliferation, migration and invasion. Finally, we also showed that
      overexpression of miR-188-5p inhibited tumor growth in vivo. Taken together, our
      findings indicated that miR-188-5p serves as a tumor suppressor in human gastric
      cancer by targeting ZFP91, suggesting that miR-188-5p might be a promising
      therapeutic target for GC treatment.

PMID- 29471892
TI  - MicroRNA-935 inhibits proliferation and invasion of osteosarcoma cells by
      directly targeting High mobility group box 1.
AB  - Substantial studies have suggested that microRNAs (miRNAs) are dysregulated in
      osteosarcoma (OS), which is implicated in OS initiation and progression.
      Therefore, knowledge of aberrantly expressed miRNAs in OS may provide novel
      mechanistic insights into the tumorigenesis and tumor development of OS and
      facilitate therapeutic methods for patients with this aggressive bone neoplasm.
      In this study, data obtained from reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR) revealed that miR-935 was significantly decreased in OS
      tissues and cell lines. Restoration expression of miR-935 obviously restricted
      proliferation and invasion of OS cells. In addition, high mobility group box 1
      (HMGB1) was predicted to be a putative target of miR-935. Subsequent luciferase
      reporter assay, RT-qPCR and Western blot analysis confirmed that miR-935 could
      directly target the 3'-untranslated region of HMGB1 and negatively regulated
      HMGB1 expression in OS cells. Furthermore, a significant negative association was
      found between miR-935 and HMGB1 mRNA expression in OS tissues. Rescue experiments
      showed that recovered HMGB1 expression partially rescued miR-935-induced
      suppression of cell proliferation and invasion in OS. These results provide first
      evidence for the suppressive roles of miR-935 in OS by directly targeting HMGB1,
      suggesting that miR-935 may be a potential candidate for the treatment of
      patients with this disease.

PMID- 29471893
TI  - MiR-363-3p inhibits osteosarcoma cell proliferation and invasion via targeting
      SOX4.
AB  - MiR-363-3p has been proven to suppress tumor growth and metastasis in various
      human cancers. However, the function of miR-363-3p in osteosarcoma (OS) has not
      been determined. In our study, we found that the expression of miR-363-3p was
      significantly downregulated in OS tissues compared with adjacent normal tissues.
      And miR-363-3p expression was associated with the poor overall survival rate of
      OS patients. Moreover, we found that overexpression of miR-363-3p markedly
      inhibited the proliferation, migration and invasion of U2OS and MG63 cells.
      Moreover, we found that SOX4 was a direct target of miR-363-3p in OS cells.
      Overexpression of miR-363-3p significantly inhibited the expression of SOX4. And
      their expression levels were negatively correlated in OS tissues. Finally, we
      found that restoration of SOX4 attenuated the suppressive effects of miR-363-3p
      on the proliferation, migration, and invasion of U2OS and MG63 cells. Therefore,
      our findings demonstrated that miR-363-3p served as a tumor suppressor in OS
      tissues by targeting SOX4.

PMID- 29471894
TI  - MiR-615 inhibits prostate cancer cell proliferation and invasion by directly
      targeting Cyclin D2.
AB  - Previous studies have reported that miR-615 exerts a tumor suppressor in some
      tumors, such as esophageal squamous cellcarcinoma and non-small cell lung cancer.
      However, the role of miR-615 in prostate cancer cells has not been defined. Here,
      we found that miR-615 was downregulated in prostate cancer tissues and cell
      lines. And overexpression of miR-615 in PC-3 cells significantly inhibited
      cellular proliferation, migration and invasion. Moreover, overexpression of miR
      615 delayed tumor growth in vivo. In term of mechanism, we found that Cyclin D2
      is a target gene of miR-615 in prostate cancer. We showed that miR-615 could bind
      to the 3?-UTR region of CCND2 mRNA and inhibit its expression. And there was a
      negatively correlation between the expression of miR-615 and CCND2 in prostate
      cancer tissues. Moreover, restoration of Cyclin D2 abolished the inhibitory
      effects of miR-615 on the proliferation, migration and invasion of prostate
      cancer cells. Taken together, our study identified miR-615 as a tumor suppressor
      by targeting Cyclin D2 in prostate cancer.

PMID- 29471895
TI  - ETV6/FLT3 Fusion Is a Novel Client Protein of Hsp90.
AB  - FMS-like tyrosine kinase-3 fragments from exon 14 to the end without any
      mutations or deletions have been reported to fuse to ETV6 (TEL) in a few cases of
      myeloid/lymphoid neoplasms with eosinophilia carrying a translocation
      t(12;13)(p13;q12). This fusion protein confers constitutive activation on the
      FLT3 fragment and induces factor-independent growth in transfected Ba/F3 cells,
      indicating that it is an oncoprotein. However, the mechanism controlling the
      stability of this oncoprotein is unknown. In this study, we focus on finding
      factors controlling the stability of ETV6/FLT3. We have shown that the stability
      of ETV6/FLT3 is regulated by the Hsp90 chaperone. ETV6/FLT3 fusion protein forms
      a complex with Hsp90 by coimmunoprecipitation analyses using an Hsp90 antibody.
      The association between ETV6/FLT3 fusion protein and Hsp90 was impaired after
      treating ETV6/FLT3 transient transfection cos7 cells with 17-allylamino-17
      demethoxygeldanamycin (17-AAG). 17-AAG induced a time- and dose-dependent
      downregulation of ectopically expressed ETV6/FLT3 protein in cos7 and HeLa
      transfected cells. By using cycloheximide to block new protein translation, we
      found that 17-AAG accelerated the decay of ETV6/FLT3. Our findings could
      contribute to more understanding of the ETV6/FLT3 regulation through Hsp90
      chaperone and open the way to finding effective treatment strategies for this
      rare disease.

PMID- 29471898
TI  - Towards patient-centred care: analysing TB treatment literacy documents and
      adherence discourses.

PMID- 29471897
TI  - The tip of the iceberg.

PMID- 29471899
TI  - Principles for constructing a tuberculosis treatment regimen: the role and
      definition of core and companion drugs.
AB  - Current World Health Organization guidelines for the formulation of treatment
      regimens for multidrug-resistant tuberculosis (MDR-TB) pay too little attention
      to the microbiological activity of anti-tuberculosis drugs. Here, we draw lessons
      from the pioneering work done on shorter MDR-TB treatment regimens and the
      current knowledge of the bactericidal and sterilizing properties of the drugs to
      inform the composition of treatment regimens for MDR-TB. We propose to reserve
      the term 'core drug' for the one drug in a regimen that contributes most to
      relapse-free cure. The core drug has both moderate to high bactericidal and
      sterilizing activity, is given throughout treatment, is well tolerated, and has
      no cross-resistance with the core drug used in the previous regimen. Currently
      used core drugs include rifampicin in the first-line 6-month regimen, and fourth
      generation fluoroquinolones and bedaquiline in regimens for drug-resistant TB.
      All other drugs are 'companion drugs', used to avert treatment failure due to
      acquired drug resistance against the core drug. Some also help further reduce the
      risk of relapse. Moreover, toxic drugs should be avoided if there is an
      alternative. A regimen must always include the core drug, plus at least one
      companion drug with high bactericidal activity, a second bactericidal companion
      drug, plus two sterilizing companion drugs.

PMID- 29471900
TI  - Prevalence of latent tuberculous infection among adults in the general population
      of Ca Mau, Viet Nam.
AB  - SETTING: The study was conducted in a randomly selected sample of persons aged
      ?15 years living in Ca Mau Province, southern Viet Nam. OBJECTIVE: To estimate
      the prevalence of latent tuberculous infection (LTBI) in the general adult
      population of this province of Viet Nam. The secondary objective was to examine
      age and sex differences in prevalence. DESIGN: A cross-sectional survey was
      conducted in a cluster-random sample of the population. Clusters were
      subcommunes. The presence of LTBI was assessed using the QuantiFERON(r)-TB Gold
      In-Tube test system. RESULTS: QuantiFERON tests were performed among 1319 persons
      aged ?15 years (77.7% of those selected). The overall prevalence of positive
      tests was 36.8% (95%CI 33.4-40.3). The prevalence of a positive test was lower in
      females than in males (31.0% vs. 44.7%, OR 0.57, 95%CI 0.45-0.72, P < 0.0001).
      The prevalence of positive tests increased with increasing age quintile (P <
      0.0001). CONCLUSION: More than one third of the general adult population in a
      province in southern Viet Nam have evidence of LTBI. Although LTBI prevalence is
      higher in males, the sex difference is not as great as that for TB notification
      rates.

PMID- 29471901
TI  - Investigating a tuberculosis cluster among Filipino health care workers in a low
      incidence country.
AB  - SETTING: Nearly 8% of adult tuberculosis (TB) cases in England, Wales and
      Northern Ireland (EW&NI) occur among health care workers (HCWs), the majority of
      whom are from high TB incidence countries. OBJECTIVES: To determine if a TB
      cluster containing multiple HCWs was due to nosocomial transmission. METHODS: A
      cluster of TB cases notified in EW&NI from 2009 to 2014, with indistinguishable
      24-locus mycobacterial interspersed repetitive unit-variable number of tandem
      repeats (MIRU-VNTR) profiles, was identified through routine national cluster
      review. Cases were investigated to identify epidemiological links, and
      occupational health (OH) information was collected for HCW cases. To further
      discriminate strains, typing of eight additional loci was conducted. RESULTS: Of
      the 53 cases identified, 22 were HCWs. The majority (n = 43), including 21 HCWs,
      were born in the Philippines. Additional typing split the cluster into three
      subclusters and seven unique strains. No epidemiological links were identified
      beyond one household and a common residential area. HCWs in this cluster received
      no or inadequate OH assessment. CONCLUSIONS: The MIRU-VNTR profile of this
      cluster probably reflects common endemic strains circulating in the Philippines,
      with reactivation occurring in the UK. Furthermore, 32-locus typing showed that
      24-locus MIRU-VNTR failed to distinguish strain diversity. The lack of OH
      assessment indicates that latent tuberculous infection could have been identified
      and treated, thereby preventing active cases from occurring.

PMID- 29471902
TI  - Under-reporting of tuberculosis in Praia, Cape Verde, from 2006 to 2012.
AB  - SETTING: According to World Health Organization (WHO) estimates, the under
      reporting rate for tuberculosis (TB) in Cape Verde between 2006 and 2012 was 49%.
      However, the WHO recognises the challenges associated with this estimation
      process and recommends implementing other methods, such as record linkage, to
      combat TB under-reporting. OBJECTIVES: To estimate and analyse under-reporting of
      cases by TB surveillance health units and to evaluate TB cases retrieved from
      other TB diagnostic sources in Praia, Cape Verde, from 2006 to 2012. DESIGN: This
      cross-sectional study evaluated under-reporting using the following data: 1) the
      under-reporting index from TB reporting health units (RHUs), where the number of
      validated TB cases from RHUs was compared with data from the National Programme
      for the Fight against Tuberculosis and Leprosy (NPFTL); and 2) the under
      reporting index among overall data sources, or a comparison of the number of all
      validated TB cases from all sources with NPFTL data. RESULTS: The TB under
      reporting rate was 40% in Praia during the study period, and results were
      influenced by laboratory findings. CONCLUSION: The TB under-reporting rate was
      very similar to the rate estimated by the WHO. TB surveillance must be improved
      to reduce under-reporting.

PMID- 29471903
TI  - Estimating the magnitude of pulmonary tuberculosis patients missed by primary
      health care clinics in South Africa.
AB  - SETTING: The present study was conducted at 20 randomly selected primary health
      clinics across Buffalo City Metropolitan Health District, a high TB burden
      district in South Africa. OBJECTIVE: To estimate the proportion of TB patients
      missed by primary health clinics. DESIGN: We enrolled 1255 TB-symptomatic
      individuals exiting primary health clinics between March and December 2015.
      Participants were interviewed and asked to provide sputum for Xpert(r) MTB/RIF
      testing. RESULTS: Clinic staff screened 79.1% of participants seeking care for TB
      related symptoms and 21.9% of those attending a clinic for other reasons (P <
      0.001). Of those screened by clinic staff, 21.5% reported submitting sputum,
      although only 9.8% had available results. Study staff tested sputum from 779
      participants not tested by clinic staff. Of these, 39 (5.0%) individuals tested
      positive for TB, three of whom were rifampicin-resistant; 15/39 (38.5%) were
      never screened and 24/39 (61.5%) were screened but not tested by clinic staff. We
      estimate that the health system missed 62.9-78.5% of TB patients attending
      primary health clinics for TB-related symptoms and 89.5-100% of those attending a
      clinic for other reasons. CONCLUSION: Low rates of TB screening and testing by
      the health system resulted in missed TB patients. Universal TB screening and
      testing of symptomatic individuals should be instituted in high TB burden
      communities in South Africa.

PMID- 29471904
TI  - Completion of isoniazid preventive therapy among human immunodeficiency virus
      positive adults in urban Malawi.
AB  - SETTING: Despite worldwide scale-up of human immunodeficiency virus (HIV) care
      services, relatively few countries have implemented isoniazid preventive therapy
      (IPT). Among other programmatic concerns, IPT completion tends to be low,
      especially when not fully integrated into HIV care clinics. OBJECTIVE: To
      estimate non-completion of 6-month IPT and its predictors among HIV-positive
      adults aged ?16 years. DESIGN: A prospective cohort study nested within a cluster
      randomised trial of TB prevention was conducted between February 2012 and June
      2014. IPT for 6 months was provided with pyridoxine at study clinics. Non
      completion was defined as loss to follow-up (LTFU), death, active/presumptive TB
      or stopping IPT for any other reason. Random-effects logistic regression was used
      to determine predictors of non-completion. RESULTS: Of 1284 HIV-positive adults
      initiated on IPT, 885/1280 (69.1%) were female; the median CD4 count was 337
      cells/MUl (IQR 199-511); 320 (24.9%) did not complete IPT. After controlling for
      antiretroviral treatment status, IPT initiation year, age and sex, non-completion
      of IPT was associated with World Health Organization stage 3/4 (aOR 1.76, 95%CI
      1.22-2.55), CD4 count 100-349 cells/MUl (aOR 1.93, 95%CI 1.10-3.38) and any
      reported side effects (aOR 22.00, 95%CI 9.45-46.71). CONCLUSION: Completion of
      IPT was suboptimal. Interventions to further improve retention should target
      immunosuppressed HIV-positive adults and address side effects.

PMID- 29471905
TI  - Delay in seeking care for tuberculosis symptoms among adults newly diagnosed with
      HIV in rural Malawi.
AB  - SETTING: Ten primary health clinics in rural Thyolo District, Malawi. OBJECTIVE:
      Tuberculosis (TB) is a common initial presentation of human immunodeficiency
      virus (HIV) infection. We investigated the time from TB symptom onset to HIV
      diagnosis to describe TB health-seeking behaviour in adults newly diagnosed with
      HIV. DESIGN: We asked adults (?18 years) about the presence and duration of TB
      symptoms at the time of receiving a new HIV diagnosis. Associations with delayed
      health seeking (defined as >30 and >90 days from the onset of TB symptoms) were
      evaluated using multivariable logistic regression. RESULTS: TB symptoms were
      reported by 416 of 1265 participants (33%), of whom 36% (150/416) had been
      symptomatic for >30 days before HIV testing. Most participants (260/416, 63%)
      were below the poverty line (US$0.41 per household member per day). Patients who
      first sought care from informal providers had an increased odds of delay of >30
      days (adjusted odds ratio [aOR] 1.6, 95%CI 0.9-2.8) or 90 days (aOR 2.0, 95%CI
      1.1-3.8). CONCLUSIONS: Delayed health seeking for TB-related symptoms was common.
      Poverty was ubiquitous, but had no clear relationship to diagnostic delay. HIV
      positive individuals who first sought care from informal providers were more
      likely to experience diagnostic delays for TB symptoms.

PMID- 29471906
TI  - Spatial clustering of drug-resistant tuberculosis in Hlabisa subdistrict, KwaZulu
      Natal, 2011-2015.
AB  - SETTING: Incidencerates of tuberculosis (TB) in South Africa are among the
      highest in the world, and drug resistance is a major concern. Understanding
      geographic variations in disease may guide targeted interventions. OBJECTIVE: To
      characterise the spatial distribution of drug-resistant TB (DR-TB) in a rural
      area of KwaZulu-Natal, South Africa, and to test for clustering. DESIGN: This was
      a cross-sectional analysis of DR-TB patients managed at a rural district hospital
      from 2011 to 2015. We mapped all patients in hospital data to local areas, and
      then linked to a population-based demographic surveillance system to map the
      patients to individual homesteads. We used kernel density estimation to visualise
      the distribution of disease and tested for clustering using spatial scan
      statistics. RESULTS: There were 489 patients with DR-TB in the subdistrict; 111
      lived in the smaller demographic surveillance area. Spatial clustering analysis
      identified a high-risk cluster (relative risk of DR-TB inside vs. outside cluster
      3.0, P < 0.001) in the south-east, a region characterised by high population
      density and a high prevalence of human immunodeficiency virus infection.
      CONCLUSION: We have demonstrated evidence of a geographic high-risk cluster of DR
      TB. This suggests that targeting interventions to spatial areas of highest risk,
      where transmission may be ongoing, could be effective.

PMID- 29471907
TI  - Multidrug-resistant tuberculosis in Australia, 1998-2012.
AB  - OBJECTIVE: To describe the epidemiology and outcomes of multidrug-resistant
      tuberculosis (MDR-TB) diagnosed in Australia between 1998 and 2012. DESIGN: A
      retrospective review was undertaken involving all patients with laboratory
      confirmed MDR-TB notified in Australia between 1998 and 2012 inclusive.
      Demographic, clinical and laboratory features are described. Clinical outcomes
      were defined according to World Health Organization definitions of treatment
      success (cure and treatment completion), treatment failure, death, loss to follow
      up (including transfer out), or not evaluated at treatment completion. RESULTS: A
      total of 244 cases of MDR-TB were diagnosed in Australia during the study period,
      representing 1.4% of all TB cases notified. The majority were born outside
      Australia, including one third in Papua New Guinea. Of those with treatment
      outcome data available, treatment success was demonstrated in 81%. Treatment
      success was positively associated with use of a second-line injectable agent.
      Those born in Papua New Guinea were less likely to achieve treatment success.
      CONCLUSION: MDR-TB is uncommon in Australia. The large number of cases born in
      Papua New Guinea, and the poorer outcomes in this cohort, represent challenges
      with cross-border management of MDR-TB in the Torres Strait. Australia has an
      ongoing role in the prevention and management of MDR-TB locally and in the
      region.

PMID- 29471908
TI  - Prognostic factors for treatment success in patients with multidrug-resistant
      tuberculosis in China.
AB  - OBJECTIVE: To examine the clinical outcomes and associated prognostic factors
      among patients with multidrug-resistant tuberculosis (MDR-TB) in China. METHODS:
      This retrospective study involved 243 patients with MDR-TB. All patients received
      standard regimens containing para-amino salicylic acid (PAS) and/or cycloserine
      (CS). The demographic, social and clinical characteristics of patients were
      recorded and the patients were followed up for 24 months. RESULTS: Treatment
      success was closely associated with young age, non-farming occupations, shorter
      history or smoking, normal urine results, initial MDR-TB treatment regimen,
      increased haemoglobin, direct bilirubin, uric acid and thyroid stimulating
      hormone (TSH) levels, and lower white blood cell, neutrophil and blood platelet
      counts (all P < 0.05). On multivariable analysis, increased haemoglobin (hazard
      ratio [HR] 1.019, 95%CI 1.007-1.032, P = 0.002) and TSH levels (HR 1.002, 95%CI
      1.006-1.039, P = 0.008), normal urine results (HR 1.541, 95%CI 1.008-2.358, P =
      0.046) and initial MDR-TB treatment regimen (HR 2.238, 95%CI 1.090-4.597, P =
      0.028) were prognostic factors for treatment success in MDR-TB. CONCLUSIONS:
      Higher haemoglobin and TSH levels, normal urine results and initial MDR-TB
      treatment regimen might predict successful treatment of MDR-TB.

PMID- 29471909
TI  - Sputum smear-positive, culture-negative state during anti-tuberculosis treatment
      in the MGIT liquid culture era.
AB  - The sputum smear-positive, culture-negative state poses a challenge for
      clinicians. Previous studies have shown that most samples with positive smears
      during the later stages of treatment are culture-negative. Earlier studies
      generally used solid culture media, which tend to be less sensitive than current
      liquid culture systems. We examined the smear-positive, culture-negative state in
      the era of MGITTM 960TM liquid cultures. We found that the smear-positive,
      culture-negative state occurred less frequently with MGIT culture, and that the
      majority of the samples with late positive smears were culture-negative,
      regardless of media type.

PMID- 29471910
TI  - Impact of quality improvement in tuberculosis laboratories in low- and lower
      middle-income countries: a systematic review.
AB  - BACKGROUND: The effect of quality improvement measures on the performance of
      diagnostic tuberculosis (TB) laboratories in low- and lower-middle-income
      countries is not known, and is the subject of this review. METHODS: Three
      databases were searched for quality improvement studies presenting data on
      performance parameters before and after the implementation of quality improvement
      interventions. RESULTS: Twenty-one studies were included in this review. Quality
      improvement measures were most frequently implemented by an external
      organization; settings targeted ranged from microscopy centers, hospitals,
      districts, regional and national reference laboratories. Quality improvement
      interventions and outcome measurements were highly heterogeneous. Most studies
      investigated interventions aimed at improving smear microscopy (n = 17). Two
      studies evaluated comprehensive quality improvement measures (n = 2) and another
      three studies focused on mycobacterial culture and drug susceptibility testing.
      Most studies showed an improvement in outcomes measured on before-after or time
      trend analysis. CONCLUSION: Quality improvement measures implemented in TB
      laboratories showed a positive impact on various outcomes. Due to the high
      heterogeneity of outcome reporting and interventions and the low quality of the
      studies, the effect size was not clear. Identification of standardized quality
      indicators and their link to the quality of patient care would improve knowledge
      in this field.

PMID- 29471911
TI  - The neuro-endocrine-immune relationship in pulmonary and pleural tuberculosis: a
      better local profile in pleural fluid.
AB  - BACKGROUND: Tuberculosis (TB) is a major health problem worldwide. In TB, the
      immune and central nervous systems modulate each other. The two main components
      of this network are the hypothalamic-pituitary-adrenal axis (HPA) and autonomic
      nervous system (ANS). OBJECTIVE: To elucidate neuro-endocrine-immune (NEI)
      interactions in pulmonary (PTB) or pleural (PLTB) TB, we analysed the
      relationship among compounds from these systems. METHODS: We quantified levels of
      catecholamines, hormones and cytokines in plasma from patients with PTB (n = 46)
      or PLTB (n = 12) and controls (n = 32), and in the pleural fluid from PLTB
      patients. Transcript expression for genes involved in glucocorticoid-related
      function (quantitative real-time polymerase chain reaction) was also analysed in
      mononuclear cells (MCs) from peripheral blood (PBMC) or pleural effusion (PEMC)
      compartments. RESULTS: Both patient groups had increased plasma levels of pro-
      and anti-inflammatory cytokines, cortisol, growth hormone (GH) and dopamine,
      whereas insulin-like growth factor 1 (IGF-1) and dehydroepiandrosterone levels
      were decreased. The pleural fluid contained increased levels of pro-inflammatory
      cytokines, GH and IGF-1 and reduced levels of steroid hormones compared with
      their plasma counterparts. PBMCs from PTB patients had increased expression of
      transcripts for 11beta-hydroxysteroid dehydrogenase (11betaHSD1) and a decreased
      glucocorticoid receptor (GR) ratio (GRalpha/GRbeta). In PLTB cases, expression of
      11betaHSD1 and GRalpha transcripts was higher in PEMCs. CONCLUSION: PTB patients
      seem to display adverse NEI dysregulation. Changes in pleural fluid are
      compatible with a more effective NEI reaction.

PMID- 29471912
TI  - Detection of tuberculosis patterns in digital photographs of chest X-ray images
      using Deep Learning: feasibility study.
AB  - OBJECTIVE: To evaluate the feasibility of Deep Learning-based detection and
      classification of pathological patterns in a set of digital photographs of chest
      X-ray (CXR) images of tuberculosis (TB) patients. MATERIALS AND METHODS: In this
      prospective, observational study, patients with previously diagnosed TB were
      enrolled. Photographs of their CXRs were taken using a consumer-grade digital
      still camera. The images were stratified by pathological patterns into classes:
      cavity, consolidation, effusion, interstitial changes, miliary pattern or normal
      examination. Image analysis was performed with commercially available Deep
      Learning software in two steps. Pathological areas were first localised; detected
      areas were then classified. Detection was assessed using receiver operating
      characteristics (ROC) analysis, and classification using a confusion matrix.
      RESULTS: The study cohort was 138 patients with human immunodeficiency virus
      (HIV) and TB co-infection (median age 34 years, IQR 28-40); 54 patients were
      female. Localisation of pathological areas was excellent (area under the ROC
      curve 0.82). The software could perfectly distinguish pleural effusions from
      intraparenchymal changes. The most frequent misclassifications were
      consolidations as cavitations, and miliary patterns as interstitial patterns (and
      vice versa). CONCLUSION: Deep Learning analysis of CXR photographs is a promising
      tool. Further efforts are needed to build larger, high-quality data sets to
      achieve better diagnostic performance.

PMID- 29471913
TI  - A rapid review of treatment literacy materials for tuberculosis patients.
AB  - OBJECTIVE: To assess available treatment literacy materials for patients
      undergoing treatment for tuberculosis (TB). DESIGN: We conducted a rapid review
      by searching the US Centers for Disease Control's Find TB Resources website and
      the websites of health departments and TB-focused organizations. We included
      English-language documents intended to educate TB patients about anti
      tuberculosis treatment. We evaluated the format, readability, and content of
      documents, and audience. We defined 12 essential content elements based on those
      previously identified as facilitating human immunodeficiency virus treatment
      literacy. RESULTS: Of the 205 documents obtained, 45 were included in our review.
      The median reading grade level was 7 (IQR 5-8). The median number of essential
      content elements present was 6 (IQR 4-8), with the most comprehensive document
      containing 11 of the 12 elements. Only two documents were written for children
      with TB or their care givers, and two for patients with drug-resistant TB. Many
      documents contained paternalistic and non-patient-centered language. CONCLUSION:
      We found few examples of comprehensive, patient-centered documents. Work is
      needed to achieve consensus as to the essential elements of TB treatment literacy
      and to create additional materials for children, patients with drug-resistant TB,
      and those with lower literacy levels.

PMID- 29471914
TI  - Molecular tests expedite the diagnosis of multidrug-resistant tuberculosis in
      childhood.

PMID- 29471915
TI  - A case report of hot tub lung: identical strains of Mycobacterium avium from the
      patient and the bathroom air.

PMID- 29471916
TI  - Errata.

PMID- 29471917
TI  - Foreword.

PMID- 29471918
TI  - Pathophysiology and Prevention of Heart Disease in Diabetes Mellitus.
AB  - Diabetes mellitus (DM) has become a public health problem worldwide, and it has
      large implications for cardiovascular disease (CVD). In this article, we discuss
      the etiology and pathophysiology of CVD in DM including the effects of abnormal
      glucose homeostasis, genetic factors, epigenetics, apoptosis, common
      pathophysiological mechanisms shared by both DM and CVD, and contributions of
      other comorbidities. We then cover the pathogenesis of both atherosclerotic
      disease and cardiomyopathy in relation to DM. Finally, we discuss the prevention
      of heart disease in DM with a focus on hypertension and dyslipidemia management,
      weight loss, lifestyle changes, antiplatelet therapy, and glycemic control.

PMID- 29471920
TI  - Correction to Lancet Diabetes Endocrinol 2015; published online Nov 24.
      http://dx.doi.org/10.1016/S2213-8587(15)00417-9.

PMID- 29471919
TI  - Dupilumab: A review of its use in the treatment of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic, pruritic immune-mediated inflammatory
      dermatosis characterized by a T helper 2 (Th2) immune response phenotype and may
      be associated with systemic inflammation. Dupilumab is an interleukin 4 (IL-4)
      receptor alpha-antagonist that inhibits IL-4 and IL-13 signaling through blockade
      of the shared IL-4alpha subunit. Blockade of IL-4/13 is effective in reducing Th2
      response. Dupilumab has recently been approved in the United States and Europe
      for the treatment of adult patients with moderate-to-severe AD. Clinical trials
      have shown that adults with moderate-to-severe AD who receive weekly or biweekly
      dupilumab injections have significantly improved clinical and patient-reported
      outcomes, including Eczema Area Severity Index, SCORing Atopic Dermatitis,
      Dermatology Life Quality Index, and itch Numeric Rating Scale scores. Concomitant
      use of topical corticosteroids along with dupilumab results in a greater
      improvement in signs and symptoms of AD than with use of dupilumab alone.
      Biomarker analyses show that dupilumab modulates the AD molecular signature and
      other Th2-associated biomarkers. Common adverse events reported in the clinical
      trials were nasopharyngitis, upper respiratory tract infection, injection site
      reactions, skin infections, and conjunctivitis. These were mild-to-moderate in
      nature, and overall rates of adverse events occurred with similar frequency
      between the treatment and placebo groups. There were no significant serious
      safety concerns identified in phase III clinical trials. Dupilumab, as
      monotherapy or with concomitant use of topical corticosteroids, can significantly
      improve clinical outcomes and quality of life in patients suffering from moderate
      to-severe AD. Ongoing studies of dupilumab will help determine the clinical
      efficacy and safety profile of its long-term use.

PMID- 29471921
TI  - Concurrent drug injection during opioid agonist treatment among people who inject
      drugs in Ukraine.
AB  - Ongoing drug use during opioid agonist treatment (OAT) negatively affects
      treatment and health outcomes, and increases treatment dropout. This study aimed
      to examine correlates of concurrent illicit drug use among OAT patients in
      Ukraine. A random sample of 434 patients currently on OAT receiving buprenorphine
      (BMT) or methadone maintenance treatment (MMT) from five cities in Ukraine were
      assessed for factors associated with self-reported concurrent illicit drug use
      during OAT using a multivariable logistic regression. Among 434 OAT patients, 100
      (23%) reported concurrent drug injecting in the previous 30 days; 28% of these
      were injecting >=20 days. While 100 (100%) of these injected opioids, 24 (24%)
      injected stimulants; 40 (40%) met criteria for polysubstance use disorder that
      included opioids, stimulants and alcohol. Independent correlates of concurrent
      drug injection included: being on MMT vs. BMT (aOR = 2.8, 95%CI = 1.4-5.8), lower
      OAT dosage (aOR = 1.7, 95%CI = 1.1-2.7), more severe addiction severity (aOR =
      2.3, 95%CI = 1.4-3.8), younger age of injection initiation (aOR = 2.3, 95%CI =
      1.3-3.9), and presence of alcohol use disorder (aOR = 2.1, 95%CI = 1.3-3.5);
      participants living with parents were negatively associated with concurrent drug
      injection. Concurrent drug use was prevalent among OAT patients in Ukraine
      indicating the urgent needs for tailored interventions and changes in OAT program
      design and implementation. Results highlight the importance of prescribing an
      adequate OAT dosage, and discrepancies between MMT and BMT programs in Ukraine
      addressing needs of OAT patients with specific characteristics such as severe
      opioid and alcohol dependence.

PMID- 29471922
TI  - Approach bias modification for cannabis use disorder: A proof-of-principle study.
AB  - BACKGROUND: More effective treatments for cannabis use disorder (CUD) are needed.
      Evidence suggests that biases in cognitive processing of drug-related stimuli are
      central to the development and maintenance of addiction. The current study
      examined the feasibility and effect of a novel intervention - approach bias
      modification (ApBM) - on cannabis approach bias and cue-reactivity. METHODS: A
      randomized, double-blind, sham-controlled proof-of-principle laboratory
      experiment investigated the effect of a four-session computerized ApBM training
      protocol on cannabis approach bias and cue-reactivity in non-treatment seeking
      adults age 18-65 with CUD (N = 33). ApBM procedures involved responding to
      cannabis or neutral stimuli using a computer joystick to model approach or
      avoidance behavior. Reactivity to tactile, olfactory, and auditory cue sets was
      assessed with physiological (blood pressure and heart rate) and subjective
      (cannabis craving) measures. Cannabis use was assessed via self-report. RESULTS:
      Participants receiving ApBM showed blunted cannabis cue-induced craving at the
      end of training compared to those in the sham-ApBM condition (p = .05). A
      preliminary gender effect on cannabis use was also found; men receiving ApBM
      reported fewer cannabis use sessions per day at the end of training compared to
      women (p = .02), while there were no differences between men and women in the
      sham condition. ApBM did not attenuate cannabis approach bias following training.
      CONCLUSION: Preliminary results indicate that ApBM may be efficacious in reducing
      cannabis cue-reactivity and improving cannabis use outcomes. While encouraging,
      the results should be interpreted with caution. Investigation of ApBM as an
      adjunct to psychosocial treatments for treatment-seeking adults with CUD is
      warranted.

PMID- 29471923
TI  - Integration of Transcendental Meditation(r) (TM) into alcohol use disorder (AUD)
      treatment.
AB  - AIMS: Maladaptive responses to stress are thought to play a role in addiction and
      relapse. Transcendental Meditation (TM) is a popular meditation technique with
      promising clinical applications. This study sought to: (a) examine the
      feasibility of providing TM during AUD treatment; (b) compare outcomes for TM vs.
      treatment as usual (TAU); and (c) investigate the relationship between TM
      practice and outcomes. METHODS: Meditation-naive adults with primary AUD (N = 60;
      35% female, 60% white) newly admitted to inpatient treatment were recruited in
      sequential cohorts (30 receiving TAU and 30 receiving TM training). Assessments
      were conducted at baseline and 3-months post-discharge. RESULTS: Integrating TM
      into inpatient AUD treatment was feasible. Uptake of TM was high (85% meditating
      on most of the past 30 days at follow-up; 61% closely adherent to recommended
      practice of twice-daily TM). Participants reported high satisfaction with TM. The
      sample as a whole improved on multiple measures after AUD treatment, but there
      were no significant differences between TM and TAU cohorts. However, those
      practicing TM twice-daily as recommended were less likely than the rest of the
      sample to return to any drinking (25% vs. 59%; p = .02) or heavy drinking post
      discharge (0% vs. 47%, p < .001). Greater regularity of TM practice was inversely
      correlated with stress, psychological distress, craving, and alcohol use at
      follow-up. CONCLUSIONS: This study established the feasibility and acceptability
      of using TM during AUD treatment. Consistently practicing TM (but not just
      learning it) was associated with better outcomes. These promising findings
      warrant further investigation in larger, controlled studies.

PMID- 29471924
TI  - Employment after beginning treatment for substance use disorders: The impact of
      race/ethnicity and client community of residence.
AB  - Employment is an important substance use treatment outcome, frequently used to
      assess individual progress during and after treatment. This study examined
      whether racial/ethnic disparities exist in employment after beginning treatment.
      It also examined the extent to which characteristics of clients' communities
      account for such disparities. Analyses are based on data that linked individual
      treatment information from Washington State's Behavioral Health Administration
      with employment data from the state's Employment Security Department. Analyses
      subsequently incorporated community-level data from the U.S. Census Bureau. The
      sample includes 10,636 adult clients (Whites, 68%; American Indians, 13%,
      Latinos, 10%; and Blacks, 8%) who had a new outpatient treatment admission to
      state-funded specialty treatment. Heckman models were used to test whether
      racial/ethnic disparities existed in the likelihood of post-admission employment,
      as well as employment duration and wages earned. Results indicated that there
      were no racial/ethnic disparities in the likelihood of employment in the year
      following treatment admission. However, compared to White clients, American
      Indian and Black clients had significantly shorter lengths of employment and
      Black clients had significantly lower wages. With few exceptions, residential
      community characteristics were associated with being employed after initiating
      treatment, but not with maintaining employment or with wages. After accounting
      for community-level variables, disparities in length of employment and earned
      wages persisted. These findings highlight the importance of considering the
      race/ethnicity of a client when examining post-treatment employment alongside
      community characteristics, and suggest that the effect of race/ethnicity and
      community characteristics on post-treatment employment may differ based on the
      stage of the employment process.

PMID- 29471925
TI  - Cost and cost-effectiveness of computerized vs. in-person motivational
      interventions in the criminal justice system.
AB  - INTRODUCTION: Although substance use is common among probationers in the United
      States, treatment initiation remains an ongoing problem. Among the explanations
      for low treatment initiation are that probationers are insufficiently motivated
      to seek treatment, and that probation staff have insufficient training and
      resources to use evidence-based strategies such as motivational interviewing. A
      web-based intervention based on motivational enhancement principles may address
      some of the challenges of initiating treatment but has not been tested to date in
      probation settings. The current study evaluated the cost-effectiveness of a
      computerized intervention, Motivational Assessment Program to Initiate Treatment
      (MAPIT), relative to face-to-face Motivational Interviewing (MI) and supervision
      as usual (SAU), delivered at the outset of probation. METHODS: The intervention
      took place in probation departments in two U.S. cities. The baseline sample
      comprised 316 participants (MAPIT = 104, MI = 103, and SAU = 109), 90% (n = 285)
      of whom completed the 6-month follow-up. Costs were estimated from study records
      and time logs kept by interventionists. The effectiveness outcome was self
      reported initiation into any treatment (formal or informal) within 2 and 6 months
      of the baseline interview. The cost-effectiveness analysis involved assessing
      dominance and computing incremental cost-effectiveness ratios and cost
      effectiveness acceptability curves. Implementation costs were used in the base
      case of the cost-effectiveness analysis, which excludes both a hypothetical
      license fee to recoup development costs and startup costs. An intent-to-treat
      approach was taken. RESULTS: MAPIT cost $79.37 per participant, which was ~$55
      lower than the MI cost of $134.27 per participant. Appointment reminders
      comprised a large proportion of the cost of the MAPIT and MI intervention arms.
      In the base case, relative to SAU, MAPIT cost $6.70 per percentage point increase
      in the probability of initiating treatment. If a decision-maker is willing to pay
      $15 or more to improve the probability of initiating treatment by 1%, estimates
      suggest she can be 70% confident that MAPIT is good value relative to SAU at the
      2-month follow-up and 90% confident that MAPIT is good value at the 6-month
      follow-up. CONCLUSIONS: Web-based MAPIT may be good value compared to in-person
      delivered alternatives. This conclusion is qualified because the results are not
      robust to narrowing the outcome to initiating formal treatment only. Further work
      should explore ways to improve access to efficacious treatment in probation
      settings.

PMID- 29471926
TI  - Do benefits restrictions limit Medicaid acceptance in addiction treatment?
      Results from a national study.
AB  - OBJECTIVE: To assess the relationship of restrictions on Medicaid benefits for
      addiction treatment to Medicaid acceptance among addiction treatment programs.
      DATA SOURCES: We collected primary data from the 2013-2014 wave of the National
      Drug Abuse Treatment System Survey. STUDY DESIGN: We created two measures of
      benefits restrictiveness. In the first, we calculated the number of addiction
      treatment services covered by each state Medicaid program. In the second, we
      calculated the total number of utilization controls imposed on each service.
      Using a mixed-effects logistic regression model, we estimated the relationship
      between state Medicaid benefit restrictiveness for addiction treatment and
      adjusted odds of Medicaid acceptance among addiction treatment programs. DATA
      COLLECTION: Study data come from a nationally-representative sample of 695
      addiction treatment programs (85.5% response rate), representatives from Medicaid
      programs in forty-seven states and the District of Columbia (response rate 92%),
      and data collected by the American Society for Addiction Medicine. PRINCIPAL
      FINDINGS: Addiction treatment programs in states with more restrictive Medicaid
      benefits for addiction treatment had lower odds of accepting Medicaid enrollees
      (AOR = 0.65; CI = 0.43, 0.97). The predicted probability of Medicaid acceptance
      was 35.4% in highly restrictive states, 48.3% in moderately restrictive states,
      and 61.2% in the least restrictive states. CONCLUSIONS: Addiction treatment
      programs are more likely to accept Medicaid in states with less restrictive
      benefits for addiction treatment. Program ownership and technological
      infrastructure also play an important role in increasing Medicaid acceptance.

PMID- 29471927
TI  - Assessment of the relationship between a written measure of empathy and an
      independently rated interview of Motivational Interviewing.
AB  - Motivational Interviewing (MI) is an evidence-based practice shown to be
      effective when working with people in treatment for substance use disorders.
      However, MI is a complex treatment modality optimized by training with feedback.
      Feedback, assessment and monitoring of treatment fidelity require measurement,
      which is typically done using audiotaped sessions. The gold standard for such
      measurement of MI skill has been an audiotaped interview, scored by a rater with
      a detailed structured instrument such as the Motivational Interviewing Treatment
      Integrity 2.0 (MITI 2.0) Coding System (Moyers, et al., 2005). The Helpful
      Responses Questionnaire (HRQ) (Miller, Hedrick, & Orlofsky, 1991) is a pen-and
      paper test of empathy (a foundational MI skill) that does not require an
      audiotaped session. A randomized trial of three different regimens for training
      counselors in MI (live supervision using Teleconferencing, Tape-based supervision
      and Workshop only) (Smith et al., 2012) offered the opportunity to evaluate the
      performance of the HRQ as a measure of MI ability, compared to the several MITI
      2.0 global scores and subscales. Participants were counselors (N=97) working at
      community-based substance use treatment programs, whose MI proficiency was
      measured at four time points: baseline (before an initial 2-day MI workshop),
      post-workshop, 8weeks post-workshop (i.e., post-supervision), and 20weeks post
      workshop with both MITI 2.0 and HRQ. HRQ total scores correlated significantly
      with the Reflection to Question Ratio from the MITI 2.0 at post-workshop
      (r=0.33), week 8 (r=0.34), and week 20 (r=0.38), and with the Spirit (r=0.32) and
      Empathy (r=0.32) global scores at week 20. Correlations of HRQ with other MITI
      2.0 subscales and time points after workshop were small and not significant. As
      predicted, HRQ scores differed between training conditions (X2(2)=7.88, p=0.02),
      with counselors assigned to live supervision achieving better HRQ scores than
      those in Workshop only. In summary, HRQ is a modestly accurate measure, mainly of
      the Reflection to Question Ratio, considered a core marker of MI skill. It is
      sensitive to training effects and may help identify counselors needing more
      intensive supervision. Given its ease of administration and scoring, HRQ may be a
      useful marker of MI skill during training efforts.

PMID- 29471929
TI  - Employment services and substance abuse treatment.
AB  - This qualitative study of over 800 participants focused on the employment
      experiences of consumers of substance abuse treatment programs to provide a
      better understanding of what employment services are offered and what needs
      treatment agencies have in the area of employment services, examining barriers
      and facilitators from both the consumer and provider perspectives. Data were
      collected via a mixed research methodology of focus groups and surveys from July
      2015 through June 2016 in a large Midwestern U.S. state. Employment is a
      challenge for persons with substance use disorders. Only a quarter of this
      study's large sample of substance abuse treatment consumers reported being cur
      rently employed; and of those consumers who reported no current employment,
      greater than half reported that their current unemployment was due to their
      substance use. Persons receiving substance abuse treatment face many challenges
      in obtaining and maintaining employment. Treatment providers identified several
      barriers to implementation of employment services. They named an array of
      resources as needed, including increased funding for supportive employment
      programs and staff appropriate to the delivery of employment services. Some
      providers believed employment services to fall outside of their scope of
      practice. Data generated through this study may inform policy to invest resources
      in employment services within substance abuse treatment settings.

PMID- 29471928
TI  - Effects of motivational interviewing fidelity on substance use treatment
      engagement in primary care.
AB  - OBJECTIVE: Primary care (PC) may be an opportune setting to engage patients with
      opioid and alcohol use disorders (OAUDs) in treatment. We examined whether
      motivational interviewing (MI) fidelity was associated with engagement in primary
      care-based OAUD treatment in an integrated behavioral health setting. METHODS: We
      coded 42 first session therapy recordings and examined whether therapist MI
      global ratings and behavior counts were associated with patient engagement,
      defined as the patient receiving one shot of extended-release injectable
      naltrexone or any combination of at least two additional behavioral therapy,
      sublingual buprenorphine/naloxone prescriptions, or OAUD-related medical visits
      within 30days of their initial behavioral therapy visit. RESULTS:
      Autonomy/support global ratings were higher in the non-engaged group (OR=0.28,
      95%CI: 0.09-0.93; p=0.037). No other MI fidelity ratings were significantly
      associated with engagement. CONCLUSION: We did not find positive associations
      between MI fidelity and engagement in primary care-based OAUD treatment. More
      research with larger samples is needed to examine how providing autonomy/support
      to patients who are not ready to change may affect engagement. PRACTICE
      IMPLICATIONS: Training providers to strategically use MI to reinforce change as
      opposed to the status quo is needed. This may be especially important in primary
      care where patients may not be specifically seeking help for their OAUDs.

PMID- 29471930
TI  - Outcomes of compulsory detention compared to community-based voluntary methadone
      maintenance treatment in Vietnam.
AB  - INTRODUCTION: In Vietnam, like many countries in East and Southeast Asia, the
      government has invested heavily in center-based compulsory treatment (CCT) as the
      mainstay demand reduction strategy for illicit drug use. This approach has been
      criticised on human rights grounds. Meanwhile, community-based voluntary
      methadone maintenance treatment (MMT) has been implemented for nearly a decade
      with promising results. To date, there have been no comparative Vietnamese
      studies of these approaches. MATERIAL AND METHODS: The study, involving 208 CCT
      participants and 384 MMT participants with heroin dependence, was a combined
      retrospective and prospective observational study conducted over three years
      between 2012 and 2014 (with data at five time-points). The primary outcome was:
      self-report heroin use (confirmed by urinalysis). The four secondary outcomes
      were: illegal behaviours, overdose, blood-borne virus (BBV) risk behaviours, and
      monthly drug expenditure. Mixed effects regression analyses, which took into
      account baseline differences between the groups, were used to analyse the data.
      This study is registered with ClinicalTrials.gov, number NCT03071315. RESULTS:
      The study found MMT was more strongly associated with four outcome measures
      compared to CCT (reduction in heroin use (beta = 3.39, SE = 0.31, p < .0001)
      (equivalent to an odds ratio of 29.67 (95% CI 21.76-40.45)), reduction in illegal
      behaviours (beta = 0.94, SE = 0.39, p < .0001), (equivalent to an odds ratio of
      2.56 (95% CI 1.79-3.78)), reduction in BBV risk behaviours (beta = 1.08, SE =
      0.17, p < .0001), (equivalent to an odds ratio of 2.94 (95% CI 2.48-3.49)), and
      reduction in monthly drug spending (beta = -VND1,515,200 (equivalent to
      US$72.00), SE = VND452,900, p < .0001)). The analyses did not support the
      hypothesis that MMT was associated with better outcomes pertaining to overdose
      (beta = -0.27, SE = 0.30, p = .62), probably due to the infrequency of these self
      reported events. CONCLUSIONS: Our observational study suggests that MMT is
      associated with greater reductions in heroin use, BBV risk behaviours, drug
      related illegal behaviours, and monthly drug spending compared with CCT. In the
      context that the CCT approach has been criticized for human rights violations,
      this study provides evidence to support the scale up of MMT and the transition of
      CCT to voluntary community based treatment.

PMID- 29471931
TI  - Coronary Artery Bypass Surgery Improves Outcomes in Patients With Diabetes and
      Left Ventricular Dysfunction.
AB  - BACKGROUND: The role of percutaneous coronary intervention (PCI) and coronary
      artery bypass grafting (CABG) in patients with diabetes mellitus (DM) and
      multivessel coronary artery disease (CAD) has been established by large trials;
      however, these trials largely excluded patients with left ventricular dysfunction
      (LVD). OBJECTIVES: The aim of this study was to determine whether treatment with
      PCI or CABG leads to improved outcomes in patients with DM, CAD, and LVD.
      METHODS: In this propensity-matched study, outcomes were compared for patients
      with CAD, DM, and LVD treated with PCI or CABG between 2004 and 2016. The primary
      outcome was major adverse cardiac and cerebrovascular events, defined as the
      composite of death, stroke, myocardial infarction, and repeat revascularization.
      Secondary outcomes were the individual components of the primary outcome.
      RESULTS: PCI compared with CABG was associated with a higher risk for major
      adverse cardiac and cerebrovascular events in cohorts with ejection fraction (EF)
      35% to 49% (p < 0.001) and <35% (p < 0.001). Treatment with PCI was associated
      with an increased risk for death in both the EF 35% to 49% and the EF <35%
      cohorts. Stroke rate did not differ between PCI and CABG in either EF cohort. PCI
      was associated with an increased rate of MI in the EF <35% cohort, and repeat
      revascularization occurred more frequently in patients treated with PCI in both
      the EF 35% to 49% cohort and the EF <35% cohort. CONCLUSIONS: At long-term follow
      up, patients with CAD, DM, and LVD treated with CABG exhibited a significantly
      lower incidence of major adverse cardiac and cerebrovascular events and better
      long-term survival over PCI, without a higher risk for stroke.

PMID- 29471932
TI  - CABG or PCI for Diabetic Patients With Left Ventricular Dysfunction: Closing in
      on the Truth?

PMID- 29471934
TI  - Which Stent Should We Select for the Left Main?

PMID- 29471933
TI  - Safety and Effectiveness of Second-Generation Drug-Eluting Stents in Patients
      With Left Main Coronary Artery Disease.
AB  - BACKGROUND: Limited data are available on the relative performances between
      different types of drug-eluting stents (DES) for obstructive left main coronary
      artery disease (LMCAD). OBJECTIVES: This study sought to compare effectiveness
      and safety profiles of various second-generation DES for LMCAD in real-world
      clinical practice. METHODS: Among 4,470 patients in 3, multicenter, prospective
      registries (IRIS-DES [Interventional Cardiology Research Incorporation Society
      Drug-Eluting Stents] registry, the IRIS-MAIN [Interventional Cardiology Research
      Incorporation Society-Left MAIN Revascularization] registry, and the PRECOMBAT
      [PREmier of Randomized COMparison of Bypass Surgery versus AngioplasTy Using Drug
      Eluting Stent in Patients with Left Main Coronary Artery Disease] study) treated
      between July 2007 and July 2015, the authors identified 2,692 patients with
      significant LMCAD who received second-generation DES; 1,254 with cobalt-chromium
      everolimus-eluting stents (CoCr-EES), 232 with biodegradable polymer biolimus
      eluting stents (BP-BES), 616 with platinum-chromium EES (PtCr-EES), and 590 with
      Resolute zotarolimus-eluting stent (Re-ZES). The primary outcome was target
      vessel failure. RESULTS: The observed 3-year rates of target-vessel failure were
      not significantly different for the different types of DES (16.7% for the CoCr
      EES, 13.2% for the BP-BES, 18.7% for the PtCr-EES, and 14.7% for the Re-ZES; p =
      0.15). In multiple treatment propensity score analysis, the adjusted hazard
      ratios (HRs) for target-vessel failure were similar in between-group comparisons
      of the different DES, except for the PtCr-EES versus the BP-BES (reference; HR:
      1.60; 95% confidence interval: 1.01 to 2.54; p = 0.046). There were no
      significant differences in risk of composite of all-cause death, any myocardial
      infarction, or any revascularization and its individual components according to
      the different types of DES. Although the 3-year incidence of stent thrombosis was
      considerably low (<=1.0%) for all types of DES, between-group differences were
      observed, generally favoring the EES platforms. CONCLUSIONS: In this pooled
      analysis of 3 prospective registries involving unrestricted use of various second
      generation DES for LMCAD, we found no significant between-group differences in 3
      year risk of target-vessel failure, except for a higher risk of primary outcome
      with PtCr-EES compared to BP-BES. (Evaluation of the First, Second, and New Drug
      Eluting Stents in Routine Clinical Practice [IRIS-DES]; NCT01186133).

PMID- 29471935
TI  - Multivessel Percutaneous Coronary Intervention in Patients With ST-Segment
      Elevation Myocardial Infarction With Cardiogenic Shock.
AB  - BACKGROUND: Recent trials demonstrated a benefit of multivessel percutaneous
      coronary intervention (PCI) for noninfarct-related artery (non-IRA) stenosis over
      IRA-only PCI in patients with ST-segment elevation myocardial infarction (STEMI)
      multivessel disease. However, evidence is limited in patients with cardiogenic
      shock. OBJECTIVES: This study investigated the prognostic impact of multivessel
      PCI in patients with STEMI multivessel disease presenting with cardiogenic shock,
      using the nationwide, multicenter, prospective KAMIR-NIH (Korea Acute Myocardial
      Infarction-National Institutes of Health) registry. METHODS: Among 13,104
      consecutive patients enrolled in the KAMIR-NIH registry, we selected patients
      with STEMI with multivessel disease presenting with cardiogenic shock and who
      underwent primary PCI. Primary outcome was 1-year all-cause death, and secondary
      outcomes included patient-oriented composite outcome (a composite of all-cause
      death, any myocardial infarction, and any repeat revascularization) and its
      individual components. RESULTS: A total of 659 patients were treated by
      multivessel PCI (n = 260) or IRA-only PCI (n = 399) strategy. The risk of all
      cause death and non-IRA repeat revascularization was significantly lower in the
      multivessel PCI group than in the IRA-only PCI group (21.3% vs. 31.7%; hazard
      ratio: 0.59; 95% confidence interval: 0.43 to 0.82; p = 0.001; and 6.7% vs. 8.2%;
      hazard ratio: 0.39; 95% confidence interval: 0.17 to 0.90; p = 0.028,
      respectively). Results were consistent after multivariable regression, propensity
      score matching, and inverse probability weighting to adjust for baseline
      differences. In a multivariable model, multivessel PCI was independently
      associated with reduced risk of 1-year all-cause death and patient-oriented
      composite outcome. CONCLUSIONS: Of patients with STEMI and multivessel disease
      with cardiogenic shock, multivessel PCI was associated with a significantly lower
      risk of all-cause death and non-IRA repeat revascularization. Our data suggest
      that multivessel PCI for complete revascularization is a reasonable strategy to
      improve outcomes in patients with STEMI with cardiogenic shock.

PMID- 29471936
TI  - Revascularization Strategies in Cardiogenic Shock Patients With MVD: For Now,
      Keep it Simple.

PMID- 29471938
TI  - Revisiting Reverse Remodeling After Aortic Valve Replacement for Aortic Stenosis.

PMID- 29471937
TI  - Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic
      Stenosis.
AB  - BACKGROUND: Left ventricular (LV) hypertrophy, a key process in human cardiac
      disease, results from cellular (hypertrophy) and extracellular matrix expansion
      (interstitial fibrosis). OBJECTIVES: This study sought to investigate whether
      human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can
      regress. METHODS: Patients with symptomatic, severe AS (n = 181; aortic valve
      area index 0.4 +/- 0.1 cm2/m2) were assessed pre-aortic valve replacement (AVR)
      by echocardiography (AS severity, diastology), cardiovascular magnetic resonance
      (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N
      terminal pro-B-type natriuretic peptide and high-sensitivity troponin T), and the
      6-min walk test. CMR was used to measure the extracellular volume fraction (ECV),
      thereby deriving matrix volume (LV mass * ECV) and cell volume (LV mass * [1 -
      ECV]). Biopsy excluded occult bystander disease. Assessment was repeated at 1
      year post-AVR. RESULTS: At 1 year post-AVR in 116 pacemaker-free survivors (age
      70 +/- 10 years; 54% male), mean valve gradient had improved (48 +/- 16 mm Hg to
      12 +/- 6 mm Hg; p < 0.001), and indexed LV mass had regressed by 19% (88 +/- 26
      g/m2 to 71 +/- 19 g/m2; p < 0.001). Focal fibrosis by CMR late gadolinium
      enhancement did not change, but ECV increased (28.2 +/- 2.9% to 29.9 +/- 4.0%; p
      < 0.001): this was the result of a 16% reduction in matrix volume (25 +/- 9 ml/m2
      to 21 +/- 7 ml/m2; p < 0.001) but a proportionally greater 22% reduction in cell
      volume (64 +/- 18 ml/m2 to 50 +/- 13 ml/m2; p < 0.001). These changes were
      accompanied by improvement in diastolic function, N-terminal pro-B-type
      natriuretic peptide, 6-min walk test results, and New York Heart Association
      functional class. CONCLUSIONS: Post-AVR, focal fibrosis does not resolve, but
      diffuse fibrosis and myocardial cellular hypertrophy regress. Regression is
      accompanied by structural and functional improvements suggesting that human
      diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic
      target. (Regression of Myocardial Fibrosis After Aortic Valve Replacement;
      NCT02174471).

PMID- 29471940
TI  - Clonal Hematopoiesis Wages War on the Myocardium.

PMID- 29471941
TI  - Editor-in-Chief's Top Picks From 2017.
AB  - Each week, I record audio summaries for every article in JACC, as well as an
      issue summary. While this process has been time-consuming, I have become quite
      familiar with every paper that we publish. Thus, I personally select papers (both
      original investigations and review articles) from 15 distinct specialties each
      year for your review. In addition to my personal choices, I have included
      manuscripts that have been the most accessed or downloaded on our websites, as
      well as those selected by the JACC Editorial Board members. In order to present
      the full breadth of this important research in a consumable fashion, we will
      present these manuscripts in this issue of JACC. The highlights comprise the
      following sections: Basic & Translational Research, Cardiac Failure,
      Cardiomyopathies/Myocardial & Pericardial Diseases, Cardio-oncology, Congenital
      Heart Disease, Coronary Disease & Interventions, CVD Prevention & Health
      Promotion, Hypertension, Imaging, Metabolic & Lipid Disorders, Rhythm Disorders,
      Valvular Heart Disease, and Vascular Medicine (1-110).

PMID- 29471939
TI  - Tet2-Mediated Clonal Hematopoiesis Accelerates Heart Failure Through a Mechanism
      Involving the IL-1beta/NLRP3 Inflammasome.
AB  - BACKGROUND: Recent studies have shown that hematopoietic stem cells can undergo
      clonal expansion secondary to somatic mutations in leukemia-related genes, thus
      leading to an age-dependent accumulation of mutant leukocytes in the blood. This
      somatic mutation-related clonal hematopoiesis is common in healthy older
      individuals, but it has been associated with an increased incidence of future
      cardiovascular disease. The epigenetic regulator TET2 is frequently mutated in
      blood cells of individuals exhibiting clonal hematopoiesis. OBJECTIVES: This
      study investigated whether Tet2 mutations within hematopoietic cells can
      contribute to heart failure in 2 models of cardiac injury. METHODS: Heart failure
      was induced in mice by pressure overload, achieved by transverse aortic
      constriction or chronic ischemia induced by the permanent ligation of the left
      anterior descending artery. Competitive bone marrow transplantation strategies
      with Tet2-deficient cells were used to mimic TET2 mutation-driven clonal
      hematopoiesis. Alternatively, Tet2 was specifically ablated in myeloid cells
      using Cre recombinase expressed from the LysM promoter. RESULTS: In both
      experimental heart failure models, hematopoietic or myeloid Tet2 deficiency
      worsened cardiac remodeling and function, in parallel with increased interleukin
      1beta (IL-1beta) expression. Treatment with a selective NLRP3 inflammasome
      inhibitor protected against the development of heart failure and eliminated the
      differences in cardiac parameters between Tet2-deficient and wild-type mice.
      CONCLUSIONS: Tet2 deficiency in hematopoietic cells is associated with greater
      cardiac dysfunction in murine models of heart failure as a result of elevated IL
      1beta signaling. These data suggest that individuals with TET2-mediated clonal
      hematopoiesis may be at greater risk of developing heart failure and respond
      better to IL-1beta-NLRP3 inflammasome inhibition.

PMID- 29471942
TI  - ACC Appropriate Use Criteria Methodology: 2018 Update: A Report of the American
      College of Cardiology Appropriate Use Criteria Task Force.

PMID- 29471943
TI  - State of the States 2017.

PMID- 29471944
TI  - Effect of NT-proBNP-Guided Therapy on All-Cause Mortality in Chronic Heart
      Failure With Reduced Ejection Fraction.

PMID- 29471945
TI  - PCSK9 as a Positive Modulator of Platelet Activation.

PMID- 29471946
TI  - Effect of Cocaine on Coronary Microvasculature.

PMID- 29471948
TI  - Seeking Quality Cardiac Care: Is Public Reporting the Answer?

PMID- 29471947
TI  - Appropriateness and Outcomes of Percutaneous Coronary Intervention at Top-Ranked
      and Nonranked Hospitals in the United States.
AB  - OBJECTIVES: This study sought to compare the appropriate use and outcomes of
      percutaneous coronary intervention (PCI) between top-ranked and nonranked
      hospitals. BACKGROUND: The U.S. News & World Report "Best Hospitals" rankings are
      an influential consumer-directed publication of hospital quality, and are
      commonly used in promotional campaigns by hospital systems. METHODS: Hospitals in
      the National Cardiovascular Data Registry CathPCI registry between July 1, 2014,
      and June 30, 2015, were classified as top-ranked if they were included in the
      2015 U.S. News & World Report 50 best "Cardiology and Heart Surgery" hospitals.
      The remaining were classified as nonranked. We compared in-hospital mortality,
      post-procedural bleeding, post-procedural acute kidney injury, and the proportion
      of appropriate PCI procedures between top-ranked and nonranked hospitals.
      RESULTS: A total of 509,153 PCIs at 654 hospitals were included, of which 55,550
      (10.9%) were performed at 44 top-ranked hospitals. After adjusting for patient
      case mix, PCIs performed at top-ranked hospitals had similar odds of in-hospital
      mortality (adjusted odds ratio [aOR]: 0.96; 95% confidence interval [CI]: 0.83 to
      1.12; p = 0.64), acute kidney injury (aOR: 1.10; 95% CI: 0.98 to 1.22; p =
      0.099), and bleeding (aOR: 1.15; 95% CI: 0.99 to 1.31; p = 0.052). Top-ranked
      hospitals had a slightly lower proportion of appropriate PCI compared with
      nonranked hospitals (89.2% vs. 92.8%; OR: 0.56; 95% CI: 0.45 to 0.69; p < 0.001).
      CONCLUSIONS: PCI performed at top-ranked hospitals was not associated with
      superior outcomes compared with PCI at nonranked hospitals. The inclusion of
      metrics based on clinical data may be important for hospital quality rankings.

PMID- 29471950
TI  - Treatment Strategy Change After Routine Pressure Wire Assessment for Coronary
      Artery Disease: What You See Is "NOT" What You Get.

PMID- 29471949
TI  - Impact of Routine Invasive Physiology at Time of Angiography in Patients With
      Multivessel Coronary Artery Disease on Reclassification of Revascularization
      Strategy: Results From the DEFINE REAL Study.
AB  - OBJECTIVES: This study sought to prospectively assess the impact of routine
      invasive physiology at the time of angiography on reclassification of therapeutic
      management of multivessel disease (MVD) patients, and to assess how
      implementation of instantaneous wave-free ratio (iFR) alters the process.
      BACKGROUND: Routine invasive physiology in intermediate coronary lesions at the
      time of diagnostic angiography, primarily in patients with single-vessel disease
      and using fractional flow reserve (FFR), reclassifies coronary revascularization
      management in 26% to 44% of patients. The role of invasive physiology in patients
      with MVD is unclear. METHODS: In 18 centers, 484 patients undergoing diagnostic
      angiography disclosing MVD with lesions >40% by visual assessment were included.
      Investigators were asked to prospectively define their initial management
      strategy based on angiography and clinical information. Invasive physiology (FFR
      or iFR driven) was then performed and final strategy defined. Initial and final
      vessel, patient, procedural, and overall management were described.
      Reclassification was defined as the difference between initial and final
      strategy. RESULTS: The majority of patients were clinically stable (82.2%). Two-
      and 3-vessel disease was present in 73.3% and 26.7% of patients, respectively.
      Lesions investigated were "intermediate" with median percent stenosis, median
      FFR, and median iFR at 60% (interquartile range [IQR]: 50% to 70%), 0.84 (IQR:
      0.78 to 0.90), and 0.92 (IQR: 0.85 to 0.96), respectively. Vessel management was
      reclassified by physiology in 30.0% (249 of 828) of vessels. Patient and overall
      management were reclassified in 26.9% (130 of 484) and 45.7% (211 of 484) of
      patients, respectively. Reclassification rates were high irrespective of initial
      management (optimal medical therapy, percutaneous coronary intervention, or
      coronary artery bypass grafting), and performance and results of pre-procedural
      noninvasive tests. Reclassification of overall management in particular increased
      with the number of vessels investigated (1 vessel: 37.3%; 2 vessels: 45.0%; 3
      vessels: 66.7%; p = 0.002). Incorporating iFR in the decision process was
      associated with investigation of more vessels (p = 0.04) and higher
      reclassification (p = 0.0001). CONCLUSIONS: In patients with MVD and intermediate
      coronary lesions, invasive physiology at time of angiography reclassifies
      revascularization strategy in a large proportion of cases (26.9%) and
      investigation of more vessels is associated with higher reclassification rates.

PMID- 29471951
TI  - Contemporary Patterns of Early Coronary Angiography Use in Patients With Non-ST
      Segment Elevation Myocardial Infarction in the United States: Insights From the
      National Cardiovascular Data Registry Acute Coronary Treatment and Intervention
      Outcomes Network Registry.
AB  - OBJECTIVES: The study sought to characterize patient- and hospital-level
      variation in early angiography use among non-ST-segment elevation myocardial
      infarction (NSTEMI) patients. BACKGROUND: Contemporary implementation of
      guideline recommendations for early angiography use in NSTEMI patients in the
      United States have not been described. METHODS: The study analyzed NSTEMI
      patients included in ACTION (Acute Coronary Treatment and Intervention Outcomes
      Network) registry (2012 to 2014) who underwent in-hospital angiography. Timing of
      angiography was categorized as early (<=24 h) vs. delayed (>24 h). The study
      evaluated factors associated with early angiography, hospital-level variation in
      early angiography use, and the relationship with quality-of-care measures.
      RESULTS: A total of 79,760 of 138,688 (57.5%) patients underwent early
      angiography. Factors most strongly associated with delayed angiography included
      weekend or holiday presentation, lower initial troponin ratio values, higher
      initial creatinine values, heart failure on presentation, and older age. Median
      hospital-level use of early angiography was 58.5% with wide variation across
      hospitals (21.7% to 100.0%). Patient characteristics did not differ substantially
      across hospitals grouped by tertiles of early angiography use (low, middle, and
      high). Hospitals in the highest tertile tended to more commonly use guideline
      recommended medications and had higher defect-free care quality scores.
      CONCLUSIONS: In contemporary U.S. practice, high-risk clinical characteristics
      were associated with lower use of early angiography in NSTEMI patients; hospital
      level use of early angiography varied widely despite few differences in case mix.
      Hospitals that most commonly utilized early angiography also had higher quality
      of-care metrics, highlighting the need for improved NSTEMI guideline adherence.

PMID- 29471952
TI  - Behind the Times?: Optimal Timing of an Invasive Strategy in Non-ST-Segment
      Elevation Acute Coronary Syndromes.

PMID- 29471953
TI  - Improvement of Risk Prediction After Transcatheter Aortic Valve Replacement by
      Combining Frailty With Conventional Risk Scores.
AB  - OBJECTIVES: This study sought to evaluate whether frailty improves mortality
      prediction in combination with the conventional scores. BACKGROUND: European
      System for Cardiac Operative Risk Evaluation (EuroSCORE) or Society of Thoracic
      Surgeons (STS) score have not been evaluated in combined models with frailty for
      mortality prediction after transcatheter aortic valve replacement (TAVR).
      METHODS: This prospective cohort comprised 330 consecutive TAVR patients >=70
      years of age. Conventional scores and a frailty index (based on assessment of
      cognition, mobility, nutrition, and activities of daily living) were evaluated to
      predict 1-year all-cause mortality using Cox proportional hazards regression
      (providing hazard ratios [HRs] with confidence intervals [CIs]) and measures of
      test performance (providing likelihood ratio [LR] chi-square test statistic and C
      statistic [CS]). RESULTS: All risk scores were predictive of the outcome
      (EuroSCORE, HR: 1.90 [95% CI: 1.45 to 2.48], LR chi-square test statistic 19.29,
      C-statistic 0.67; STS score, HR: 1.51 [95% CI: 1.21 to 1.88], LR chi-square test
      statistic 11.05, C-statistic 0.64; frailty index, HR: 3.29 [95% CI: 1.98 to
      5.47], LR chi-square test statistic 22.28, C-statistic 0.66). A combination of
      the frailty index with either EuroSCORE (LR chi-square test statistic 38.27, C
      statistic 0.72) or STS score (LR chi-square test statistic 28.71, C-statistic
      0.68) improved mortality prediction. The frailty index accounted for 58.2% and
      77.6% of the predictive information in the combined model with EuroSCORE and STS
      score, respectively. Net reclassification improvement and integrated
      discrimination improvement confirmed that the added frailty index improved risk
      prediction. CONCLUSIONS: This is the first study showing that the assessment of
      frailty significantly enhances prediction of 1-year mortality after TAVR in
      combined risk models with conventional risk scores and relevantly contributes to
      this improvement.

PMID- 29471954
TI  - Frailty: An Important Measure in Patients Considered for Transcatheter Aortic
      Valve Replacement.

PMID- 29471955
TI  - A Case of Successful Reopening of Left Main Coronary Artery Occlusion After
      Transcatheter Aortic Valve Replacement.

PMID- 29471957
TI  - The COFFEE Trial (COmparison of Fractional Flow Reserve Measurements through 4
      FrEnch versus 6 FrEnch Diagnostic Catheter).

PMID- 29471956
TI  - First-in-Human Use of a Retention-Enhanced Catheter for Endomyocardial Cell
      Delivery.

PMID- 29471958
TI  - Multimodality Imaging of a Very Late Thrombosis of a Sutureless Aortic
      Prosthesis.

PMID- 29471959
TI  - Hypertrophic Left Ventricle With Small Cavity and Severe Aortic Angulation: A
      Dangerous Association in Case of Transcatheter Aortic Valve Replacement.

PMID- 29471960
TI  - Overview of autosomal dominant polycystic kidney disease in the south of Spain.
AB  - INTRODUCTION: Although autosomal dominant polycystic kidney disease is the most
      common hereditary kidney disease, available data tend to be limited to after
      initiation of renal replacement therapy. OBJECTIVE: To ascertain an overview of
      autosomal dominant polycystic kidney disease within the health area of Granada in
      southern Spain. MATERIAL AND METHODS: From January 2007 to December 2016, we
      collected clinical, family and demographic information about all patients with
      autosomal dominant polycystic kidney disease, irrespective of whether or not they
      were treated with RRT, in the Granada health area. The computer software SPSS
      15.0 and GenoPro were used. RESULTS: 50.6% of the 1,107 diagnosed patients were
      men. 99.1% were Caucasian and 4-6 generations/family were studied. The
      geographical distribution was heterogeneous. There was no family history in
      2.43%. The mean age of diagnosis was 34.0+/-17.80 years and the diagnosis was
      made after having offspring in 57.7% of cases. The main reason for diagnosis was
      family history (46.4%). The mean age of initiation of renal replacement therapy
      was 54.2+/-11.05 years. 96.3% of the deceased had some degree of renal failure at
      the time of death. The mean age of death was 60.9+/-14.10 years, the main cause
      of death being unknown in 33.5% of cases, followed by cardiovascular (27.8%).
      CONCLUSIONS: Cases and families were concentrated in certain geographical areas
      and a significant number of individuals were undiagnosed prior to cardiovascular
      death or diagnosed late after reproduction. Given that there is currently no
      curative treatment, the primary prevention strategy of preimplantation genetic
      diagnosis should play a leading role.

PMID- 29471962
TI  - Influenza: Our Old Fickle Foe.

PMID- 29471961
TI  - Acute Kidney Injury due to granulomatous interstitial nephritis induced by
      tramadol administration.

PMID- 29471963
TI  - [Hepatotoxicity of tyrosine kinase inhibitors: Mechanisms involved and practical
      implications].
AB  - Tyrosine kinase inhibitors (TKIs) are used for the targeted treatment of solid
      cancers. TKIs produce a variable incidence of liver adverse events (5-25%) which
      can progress to severe liver injury in a minority of patients if treatment is
      maintained despite ongoing injury. This risk requires careful patient management
      to maintain treatment benefit without harm. This review highlights the various
      mechanisms of idiosyncratic hepatotoxicity, the formation of reactive metabolites
      and how this leads to toxicity. These critical events depend of the drug-specific
      characteristics of each TKI and the patient risk factors, especially genetic
      characterization. With improved understanding of the mechanisms leading to
      hepatotoxicity, several strategies have been adopted to prevent or treat this
      side effect. Recommendations on liver function liver test monitoring have been
      proposed according to each TKI.

PMID- 29471964
TI  - Use of integrative services is associated with maintenance of work schedule
      during and after cancer treatment.
AB  - INTRODUCTION: Cancer diagnosis affects employment status. Our health network
      offers supportive services to cancer patients. We hypothesized patients who used
      these services were more likely to continue to work during and after treatment.
      METHODS: A mailed survey was used to assess employment before, during, and after
      treatment, and support services used. Chi-square analysis was performed. RESULTS:
      The response rate was 34% (273/782). 87% of patients worked full or part time
      before cancer diagnosis, 68.8% continued to work during treatment, and 73.9%
      returned to work after treatment. 61% of patients used at least one type of
      support service. Patients who had no change in work status during treatment and
      who returned to work less than one month after treatment were more likely to use
      services. CONCLUSIONS: Most patients used support services, continued to work
      during treatment, and returned to pre-cancer employment status. Physicians should
      encourage patients to pursue supportive therapies.

PMID- 29471965
TI  - Early experience with a combined surgical and obstetrics/gynecology clerkship: We
      do get along.
AB  - BACKGROUND: In 2012, the Ohio State University College of Medicine (OSUCOM)
      implemented a new undergraduate medical curriculum. We compare outcomes of a
      third year traditional clerkship format to a combined Surgery and
      Obstetrics/Gynecology 'ring'. METHODS: Performance outcomes of 4 consecutive
      classes were compared between pre- (2014, 2015) and post-curricular revision
      (2016, 2017). RESULTS: Three hundred ninety-one students consented use of their
      educational data for research. We examined medical knowledge (NBME scores, USMLE
      Step 1 and Step 2 CK scores) and student satisfaction between pre- and post
      curricular revision. Results demonstrated no statistically significant difference
      in the Obstetrics/Gynecology NBME shelf examination. Surgery NBME and USMLE Step
      2 scores were increased and statistically significant but satisfaction of both
      disciplines was higher pre-curricular revision. CONCLUSION: Medical knowledge
      outcomes in this combined 'ring' were similar to or higher than performance in
      previous years'. Future analyses are needed to assess the impact of OSUCOM
      curricular revision.

PMID- 29471966
TI  - Oral health management considerations for patients with sickle cell disease.
AB  - Sickle cell disease (SCD) can affect many systems in the body including the oral
      cavity. This necessitates modifications in oral health care management of these
      patients. The purpose of this paper is to make recommendations for management of
      SCD patients according to their oral health care needs based on the known
      findings.

PMID- 29471967
TI  - Blistering During Phototherapy.

PMID- 29471968
TI  - An adaptive three-stage extended Kalman filter for nonlinear discrete-time system
      in presence of unknown inputs.
AB  - Considering the performances of conventional Kalman filter may seriously degrade
      when it suffers stochastic faults and unknown input, which is very common in
      engineering problems, a new type of adaptive three-stage extended Kalman filter
      (AThSEKF) is proposed to solve state and fault estimation in nonlinear discrete
      time system under these conditions. The three-stage UV transformation and
      adaptive forgetting factor are introduced for derivation, and by comparing with
      the adaptive augmented state extended Kalman filter, it is proven to be uniformly
      asymptotically stable. Furthermore, the adaptive three-stage extended Kalman
      filter is applied to a two-dimensional radar tracking scenario to illustrate the
      effect, and the performance is compared with that of conventional three stage
      extended Kalman filter (ThSEKF) and the adaptive two-stage extended Kalman filter
      (ATEKF). The results show that the adaptive three-stage extended Kalman filter is
      more effective than these two filters when facing the nonlinear discrete-time
      systems with information of unknown inputs not perfectly known.

PMID- 29471969
TI  - Improved results on state feedback stabilization for a networked control system
      with additive time-varying delay components' controller.
AB  - This paper investigates the problems of stability and stabilization for a
      networked control system (NCS) with additive time-varying delay components'
      controller. Firstly, stability of a NCS with additive time-varying delays is
      investigated. A novel approach with free parameters is proposed. By constructing
      a new Lyapunov-Krasovskii functional (LKF) with two free parameters, stability
      criteria are obtained. The obtained stability criteria depend not only on upper
      bounds of delays but also free parameters. In addition, input-output method is
      extended to study the stability problem for the NCS. Compared with other
      approaches such as input-output method, the free-parameter approach is more
      flexible and effective in reducing the conservatism. Then, based on the stability
      results, a state feedback controller is designed to guarantee the asymptotically
      stable of the closed-loop systems. Finally, numerical examples are provided to
      show the effectiveness and less conservatism of the proposed results.

PMID- 29471970
TI  - The accuracy and precision of Kilovoltage Intrafraction Monitoring (KIM) six
      degree-of-freedom prostate motion measurements during patient treatments.
AB  - BACKGROUND AND PURPOSE: To perform a quantitative analysis of the accuracy and
      precision of Kilovoltage Intrafraction Monitoring (KIM) six degree-of-freedom
      (6DoF) prostate motion measurements during treatments. MATERIAL AND METHODS: Real
      time 6DoF prostate motion was acquired using KIM for 14 prostate cancer patients
      (377 fractions). KIM outputs the 6DoF prostate motion, combining 3D translation
      and 3D rotational motion information relative to its planning position. The
      corresponding groundtruth target motion was obtained post-treatment based on
      kV/MV triangulation. The accuracy and precision of the 6DoF KIM motion estimates
      were calculated as the mean and standard deviation differences compared with the
      ground-truth. RESULTS: The accuracy +/- precision of real-time 6DoF KIM-measured
      prostate motion were 0.2 +/- 1.3 degrees  for rotations and 0.1 +/- 0.5 mm for
      translations, respectively. The magnitude of KIM-measured motion was well
      correlated with the magnitude of ground-truth motion resulting in Pearson
      correlation coefficients of  >=0.88 in all DoF. CONCLUSIONS: The results
      demonstrate that KIM is capable of providing the real-time 6DoF prostate target
      motion during patient treatments with an accuracy +/- precision of within 0.2 +/-
      1.3 degrees  and 0.1 +/- 0.5 mm for rotation and translation, respectively. As
      KIM only requires a single X-ray imager, which is available on most modern cancer
      radiotherapy devices, there is potential for widespread adoption of this
      technology.

PMID- 29471971
TI  - Towards the Integration of Niche and Network Theories.
AB  - The quest for understanding how species interactions modulate diversity has
      progressed by theoretical and empirical advances following niche and network
      theories. Yet, niche studies have been limited to describe coexistence within
      tropic levels despite incorporating information about multi-trophic interactions.
      Network approaches could address this limitation, but they have ignored the
      structure of species interactions within trophic levels. Here we call for the
      integration of niche and network theories to reach new frontiers of knowledge
      exploring how interactions within and across trophic levels promote species
      coexistence. This integration is possible due to the strong parallelisms in the
      historical development, ecological concepts, and associated mathematical tools of
      both theories. We provide a guideline to integrate this framework with
      observational and experimental studies.

PMID- 29471972
TI  - [Author's response to the letter on the article: "Absence of proof does not
      constitute proof of absence. On the misuse of evidence-based medicine"].

PMID- 29471973
TI  - ?

PMID- 29471975
TI  - ?

PMID- 29471974
TI  - ?

PMID- 29471976
TI  - Organic contaminant removal efficiency of sodium bentonite/clay (BC) mixtures in
      high permeability regions utilizing reclaimed wastewater: A meso-scale study.
AB  - Wastewater reclamation now represents an effective measure for sustainable water
      resource management in arid regions, however wastewater components (organic
      micropollutants) may potentially impact local ecological and/or human health.
      Previous studies have shown that sodium bentonite/natural clay (BC) mixes may be
      used to effectively reduce riverbed infiltration in regions characterized by
      excessively high hydraulic conductivity. Accordingly, the current study sought to
      investigate the contaminant removal efficiency (Re) of several BC mass ratios in
      simulated dry riverbeds. Results indicate that the measured Re of NH4+-N, CODcr
      and BOD5 increased in concurrence with an increasing sodium bentonite ratio, up
      to a maximum Re of 97.4% (NH4+-N), 55.2% (CODcr), and 51.5% (BOD5). The primary
      contaminant removal site was shown to be the infiltration-reducing (BC) layer,
      accounting for approximately 40%, 60%, and 70% of NH4+-N, CODcr and BOD5 removal,
      respectively. Conversely, the removal efficiency of NO3-N was found to be low
      (<15%), while total phosphorous (TP) was found to actively leach from the
      infiltration-reduction layer, resulting in measured TP discharges 2.4-4.8 times
      those of initial infiltration values. The current study provides a technical
      baseline for the efficacy of sodium bentonite as an effective bi-functional
      material in areas utilizing reclaimed water i.e. concurrent reduction of
      infiltration rates (Function 1) and decontamination of reclaimed wastewater
      infiltration/recharge (Function 2). Findings indicate that sodium bentonite-clay
      mixes may represent a feasible alternative for managing recharge of non-potable
      aquifers with reclaimed wastewater.

PMID- 29471977
TI  - Effects of parity on productive, reproductive, metabolic and hormonal responses
      of Holstein cows.
AB  - The objective of this study was to determine the effects that parity may have on
      production, reproduction and the metabolic status of Holstein cows managed in a
      production system based on total mixed ration and pasture. Primiparous (n = 22)
      and multiparous (n = 24) cows from a dairy farm research station in Uruguay were
      used in a completely randomized design. Body weight (BW), body condition score
      (BCS) and backfat thickness (BFT) were recorded weekly from -30 to 70 days
      postpartum. Milk production was measured daily, and milk composition was
      determined weekly. Resumption of postpartum ovarian activity and progesterone
      profiles were measured three times a week based on milk progesterone. Blood was
      collected to determine the levels of glucose, insulin-like growth factor I (IGF
      1), insulin, non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB),
      albumin, total protein and cholesterol. Milk production and components were lower
      for primiparous cows (p < 0.01) than multiparous cows. Body weights were also
      lower in primiparous cows than in multiparous cows (p < 0.05); however, BCS and
      BFT were greater (p < 0.01) in primiparous cows than in multiparous cows.
      Primiparous cows had greater levels of glucose, insulin and IGF-1 and lower
      concentrations of NEFA and BHB (p < 0.01) than multiparous cows. The intervals
      from calving to first ovulation were not affected by parity; however, primiparous
      cows showed less abnormal cycles (27.2%) than multiparous cows (50.0%) (p <
      0.01). The present study found that a feeding system based on TMR and pasture was
      sufficient to produce over 25 L of milk per day without extending their calving
      to first ovulation interval in primiparous and multiparous cows. However,
      multiparous cows showed a greater imbalance in metabolic and hormonal profiles
      than primiparous cows, causing abnormal ovarian activity.

PMID- 29471978
TI  - Generalization and maintenance of functional communication training for
      individuals with developmental disabilities: A systematic and quality review.
AB  - BACKGROUND: Functional communication training (FCT) is considered an evidence
      based practice for treating problem behavior in individuals with developmental
      disabilities (e.g. autism, intellectual disabilities, down syndrome, etc.).
      However, there is little known on how to sustain behavioral change following FCT
      interventions. This systematic and quality review synthesizes the current
      literature base evaluating the maintenance and generalization of behavioral
      effects following FCT. METHOD: A systematic review identified 37 studies that met
      the pre-set inclusion criteria. Those studies were summarized in terms of: (a)
      generalization dimension, (b) generalization assessment design, (c) maintenance
      assessment design, (d) maintenance and generalization teaching strategy, and (e)
      latency to maintenance probes. All studies employed single-case research designs
      and were evaluated using the What Works Clearinghouse pilot single-case research
      standards (Kratochwill et al., 2013) as adapted by Maggin, Briesch, and
      Chafouleas (2013). Maintenance and generalization data were evaluated using a
      researcher-developed rubric based on the WWC standards. RESULTS AND DISCUSSION:
      Results indicate that 30 studies met standards or met standards with reservations
      while only six studies also met all of the maintenance and generalization
      standards. Of the six studies, five did not implement any additional strategies
      beyond the contacting natural contingencies that is inherent in the FCT
      intervention. Implications for future research and practice are discussed.

PMID- 29471979
TI  - Future alternative therapies in the pipeline for mild neonatal encephalopathy:
      Review of evidence of neuroprotection with erythropoiesis stimulating agents.

PMID- 29471980
TI  - The influence of risk labeling on risk perception and willingness to seek help in
      an experimental simulation of preventive medical examinations.
AB  - OBJECTIVE: To study the influence of the presentation of results of a preventive
      medical examination on risk perception and willingness to seek help for work
      related fatigue or being overweight. METHODS: A factorial design experiment was
      conducted, presenting workers (n = 82) with vignettes including eight scenarios
      of test results with and without an emphasis on the risk of a current or future
      health condition or a probe to seek help. Participants rated perceived risk and
      willingness to seek help (0-100 Visual Analogue Scale) as if these were their own
      results. Differences were tested with paired-sample t-tests. RESULTS: In
      scenarios emphasizing the risk of a current or future disorder, participants
      perceived higher risk and were more willing to seek help (p-values < .00).
      Slightly higher willingness to seek help scores was observed in all scenarios
      that included probes (p < .00). CONCLUSION: Risk perception and willingness to
      seek help of workers participating in a preventive medical examination were
      higher when they were told that the test results indicate a risk of a current or
      future disorder and after being advised to seek help. PRACTICE IMPLICATIONS:
      Healthcare providers should take the potential effects on risk perception and
      help-seeking into account in preventive settings.

PMID- 29471981
TI  - Methodologic Considerations for Transition Research Using the National Survey of
      Children with Special Health Care Needs: A Systematic Review of the Literature.
AB  - The purpose of this review was to describe methodologic considerations in using
      the National Survey of Children With Special Health Care Needs (NS-CSHCN) for
      transition research in terms of variable inclusion and definition of transition
      outcomes and to provide suggestions for using NS-CSHCN for transition research. A
      systematic review was conducted. Inclusion criteria included use of NS-CSHCN data
      and transition as an outcome variable. Fourteen studies were included. Ten (71%)
      studies evaluated a sample of all CSHCN. Ten (71%) articles used all four
      variables recommended by the Maternal and Child Health Bureau core outcome on
      transition. Other variables included patient-centered medical home. The NS-CSHCN
      provides a rich dataset that can be used in transition research addressing
      transition preparation from the parent perspective. Using the NS-CSHCN, we
      recommend analyzing all variables related to the Maternal and Child Health Bureau
      core outcome for transition, variables related to patient-centered medical home,
      and further analysis of specific health conditions.

PMID- 29471982
TI  - Decreasing Caregivers' Positive Attitudes Toward Spanking.
AB  - The Play Nicely program is a multimedia training program designed to teach
      caregivers and health care professionals how to manage early childhood aggression
      and to use positive parenting practices. The aim of this article is to help the
      practicing clinician determine whether the Play Nicely program should be
      incorporated into his/her practice and to evaluate whether the program is
      effective at decreasing positive attitudes toward spanking in a socioeconomically
      disadvantaged population in both a resident pediatric clinic and a community
      center. Thirty-three caregivers of children aged 2 to 5 years viewed the Play
      Nicely program and completed pre- and post-training questionnaires. Decreased
      positive attitudes toward spanking were reported after training. Favorable
      attitudes toward spanking were associated with increased use of harsher
      discipline and higher child externalizing behavior. This study provides support
      that this brief intervention is effective in a socioeconomically disadvantaged
      population, is portable, and can be used in a group setting. This program may
      serve as a prevention and population-based approach to addressing the adverse
      childhood experience of spanking.

PMID- 29471983
TI  - Current Trends in Methylotrophy.
AB  - Methylotrophy is a field of study dealing with microorganisms capable of
      utilization of compounds devoid of carbon-carbon bonds (C1 compounds). In this
      review, we highlight several emerging trends in methylotrophy. First, we discuss
      the significance of the recent discovery of lanthanide-dependent alcohol
      dehydrogenases for understanding both the occurrence and the distribution of
      methylotrophy functions among bacteria, and then we discuss the newly appreciated
      role of lanthanides in biology. Next, we describe the detection of other
      methylotrophy pathways across novel bacterial taxa and insights into the
      evolution of methylotrophy. Further, data are presented on the occurrence and
      activity of aerobic methylotrophs in hypoxic and anoxic environments, questioning
      the prior assumptions on niche separation of aerobic and anaerobic methylotrophy.
      The concept of communal function in aerobic methane oxidation is also briefly
      discussed. Finally, we review recent research in engineering methylotrophs for
      biotechnological applications as well as recent progress in engineering synthetic
      methylotrophy.

PMID- 29471985
TI  - Heart failure with preserved ejection fraction: Classification based upon
      phenotype is essential for diagnosis and treatment.
AB  - Heart failure (HF) is classified based upon the left ventricular ejection
      fraction (LVEF). Heart failure with preserved ejection fraction (HFpEF) is a
      heterogeneous disorder with increasing prevalence in the elderly that remains
      incompletely understood and inadequately treated as no therapy has shown
      favorable effects. In this review, we summarize the current theories regarding
      HFpEF pathogenesis, propose a phenotype-based classification of HFpEF, discuss
      prevention strategies, explain why clinical trials on HFpEF treatment have
      failed, and make suggestions for the future.

PMID- 29471984
TI  - Increasing Diagnosis and Treatment of Perinatal Depression in Latinas and African
      American Women: Addressing Stigma Is Not Enough.

PMID- 29471986
TI  - Molecular Cogs: Interplay between Circadian Clock and Cell Cycle.
AB  - The cell cycle and the circadian clock operate as biological oscillators whose
      timed functions are tightly regulated. Accumulating evidence illustrates the
      presence of molecular links between these two oscillators. This mutual interplay
      utilizes various coupling mechanisms, such as the use of common regulators. The
      connection between these two cyclic systems has unique interest in the context of
      aberrant cell proliferation since both of these oscillators are frequently
      misregulated in cancer cells. Further studies will provide deeper understanding
      of the detailed molecular connections between the cell cycle and the circadian
      clock and may also serve as a basis for the design of innovative therapeutic
      strategies.

PMID- 29471987
TI  - Unique contributions of Keraleeya Ayurveda in pediatric health care.
AB  - Childhood is considered as the most important phase in life, which determines the
      quality of health, well being, learning and behaviour across the lifespan. This
      may be the reason for giving the foremost position for Balacikitsa among
      Ashtangas (8 branches) of Ayurveda. The regional growth of indigenous medicine
      gave significant contribution for the development of primary health care. Kerala
      has major contribution of many authentic textbooks of Balacikitsa like
      Arogyakalpadruma, Vaidya Tarakam etc. These are more practically oriented and it
      can be considered as a physician's quick reference hand book. Many new diseases
      which are not mentioned in classical textbooks have found their place in these
      books. Medications like Praakaara yoga, Uramarunnuprayoga were administered in
      children as a mode of immunization, which helps in the maintenance of health and
      prevention of disease. Many diseases like Karappan (balavisarpa), Shakarogas etc.
      were common in Kerala and various indigenous treatment modalities were developed
      for such diseases. Single drug Prayogas with herbs like Mayaphal (galls), Tripadi
      (DesmodiumTriflorum L.), etc. and yogams like Nalikerakwatha (Putapakakalpana),
      Mukkuti (Takrakalpana) etc. were practiced commonly. Many effective therapies
      like Shashtikapindasweda, Thalapothichil (Sirolepa) etc. are an inevitable part
      of Balacikitsa. In this paper, an attempt is made to compile the theoretical
      concepts and unique practices of Balacikitsa in Kerala and to convey it's
      importance. The present article also addresses, how these vernacular books and
      traditional knowledge waned away from the Mainstream Ayurveda.

PMID- 29471988
TI  - Multicenter, Randomized Trial of Conventional Balloon Angioplasty versus
      Paclitaxel-Coated Balloon Angioplasty for the Treatment of Dysfunctioning
      Autologous Dialysis Fistulae.
AB  - PURPOSE: To investigate the potential added value of paclitaxel-coated balloon
      (PCB) angioplasty to reduce fistula dysfunction related to recurrent stenoses in
      patients undergoing hemodialysis. MATERIALS AND METHODS: A prospective,
      randomized study was conducted in 3 dialysis referral centers. From January 2013
      to October 2015, 64 patients (22 female, 42 male) with dysfunctional autologous
      dialysis fistulae were randomized to undergo conventional percutaneous balloon
      angioplasty (n = 31) or PCB angioplasty (n = 33). Procedural and postprocedural
      data were assessed. Primary patency of the fistula was evaluated at 3, 6, and 12
      months following the procedure. Statistical analysis was based on the Fisher
      exact test and independent t test. RESULTS: There were no procedural or
      postprocedural complications. After 3, 6, and 12 months of follow-up, primary
      patency rates after PCB angioplasty and percutaneous transluminal angioplasty
      (PTA) were 88% and 80% (P = .43), 67% and 65% (P = .76), and 42% and 39% (P =
      .95), respectively. CONCLUSIONS: Although primary patency rates after PCB
      angioplasty in autologous dialysis fistulae at 3, 6, and 12 months of follow-up
      are slightly better than those after PTA, the difference is not statistically
      significant.

PMID- 29471989
TI  - The Relationship Between Intradialytic Nutrition and Gastrointestinal Symptoms
      Using a Modified Version of the Gastrointestinal Symptom Rating Scale.
AB  - OBJECTIVE: Intradialytic nutrition has been shown to improve nutritional status
      in maintenance hemodialysis (HD) patients but remains controversial due in part
      to concerns over hemodynamic stability and gastrointestinal (GI) distress. There
      are limited data on the relationship between intradialytic nutrition and GI
      symptoms, possibly due to the lack of a validated tool. Therefore, we intended to
      validate a questionnaire to measure GI symptoms associated with a single HD
      treatment and determine the relationship between intradialytic nutrition and GI
      symptoms. DESIGN: Cross-sectional study. Forty-eight maintenance HD patients.
      MAIN OUTCOME MEASURE: GI symptoms and dietary intake during HD treatment.
      RESULTS: In general, we found acceptable internal consistency (Cronbach's alpha
      >0.5, exception reflux domain) and repeatability in all 5 domains of a modified
      version of the Gastrointestinal Symptom Rating Scale. The prevalence of GI
      symptoms associated with a single HD treatment (generalized score greater than 1)
      was 54.2, 43.7, 6.2, 41.7, and 45.8% for the abdominal pain, indigestion, reflux,
      diarrhea, and constipation domains, respectively. More than two-thirds of
      patients chose to eat during treatment (168.6 +/- 165.6 kcal) with the most
      commonly consumed items being candy, oral supplements, and cookies. There was no
      difference in GI symptoms among patients who did or did not eat (P > .05).
      However, the amount of total dietary fat and fiber consumed during treatment was
      associated with greater indigestion (P < .05) prior to accounting for outliers or
      multiple comparisons. CONCLUSION: In this sample, the modified version of the
      Gastrointestinal Symptom Rating Scale was a generally valid tool for measuring GI
      symptoms associated with a single HD treatment. Patients who ate during treatment
      did not experience greater GI symptoms than those who did not; however, high
      amounts of fat and fiber may be associated with greater GI symptoms. Prospective
      trials should examine the relationship between GI symptoms and dietary intake
      during treatment in HD patients.

PMID- 29471991
TI  - Nutritional Considerations for Dialysis Vegetarian Patients, Part One.

PMID- 29471992
TI  - In vivo and in vitro preparation of divinyl-132,173-cyclopheophorbide-a enol.
AB  - Divinyl-132,173-cyclopheophorbide-a enol was in vivo produced as a metabolite of
      divinyl-chlorophyll-a by protists and in vitro prepared by the intramolecular
      cyclization of methyl divinyl-pyropheophorbide-a, one of the divinyl-chlorophyll
      a derivatives. The 1H NMR spectra in CDCl3 showed that the obtained product took
      exclusively its enol form in the solution. The intramolecular cyclization of
      chlorin pi-system at the C132 and C173 positions affected the optical properties
      of such chlorophyll derivatives including the non-fluorescent emission of the
      enol.

PMID- 29471993
TI  - Live Without Regret.

PMID- 29471994
TI  - Ergonomics in the Development and Prevention of Musculoskeletal Injury in
      Interventional Radiologists.
AB  - Interventional radiology is a constantly evolving specialty overlapping with
      multiple other specialties, including cardiology, vascular surgery, orthopedic
      surgery, urology, and minimally invasive surgery. Unique ergonomic considerations
      for interventional radiology include utilization of intraoperative viewing
      monitors and personal radiation protection equipment. Work-related injuries are
      common in interventional radiologists,1 often leading to pain while performing
      procedures or during time away from work. This review article aims to identify
      the ergonomic challenges related to interventional radiology and provide
      background, guidelines, and specific recommendations for prevention of
      musculoskeletal injury.

PMID- 29471995
TI  - Should We Keep the Lead in the Aprons?
AB  - Medical staff should not be exposed to the primary X-ray beam during fluoroscopy
      guided interventional procedures (FGIP). The main source of staff exposure is
      scatter radiation from the patient, which can be significant. Although many
      aspects of X-ray exposure to the patient as well as occupational exposure to
      interventional radiologists and other staff are strongly regulated and monitored
      in most countries, it is surprising how loosely the labeling and testing of the
      protective aprons is regulated. Interventional radiologists (IRs) have to be
      experts in interventional radiology as well as in basic facts regarding ways to
      provide a satisfactory level of protection from occupational exposure. IRs,
      however, are not familiar with the apron testing methods. The accompanying
      documents provided with aprons by manufacturers may not be informative enough.
      Vendors often report apron effectiveness at a single beam quality and
      attenuation. The vendor reports repeatedly disagree with independent reports,
      which clearly show that the attenuation of these garments at other important
      unreported energies may be lower than expected. Better trust no one and check
      your protective garment yourself, or, better yet, consult a medical physicist
      when making purchasing decisions related to protective garments. Each
      interventionist should choose garments that are appropriately protective for that
      individual's practice. Review of past personal dosimetry results and consultation
      with a medical physicist can help the IR make the best decision. This article
      will help the reader to understand why all protective garments are not created
      equally, and provides some practical tools that will allow safe and healthy
      practice in FGIP.

PMID- 29471996
TI  - The Eyes Have It.
AB  - The ocular lens is one of the most susceptible structures in the body to
      radiation damage. Unfortunately, much of the traditional academic and regulatory
      thinking on thresholds to develop radiation-induced opacities or cataracts has
      proven to be false. Individual vulnerability to the effects of radiation is
      extremely variable, largely because each individual is variably genetically
      equipped to repair the damage caused by radiation. Therefore many people,
      including some unsuspecting interventional radiologists may have no, or almost
      no, threshold at all for cataract development after radiation injury. For most
      others, if there is a threshold it is a fraction of what was previously thought.
      These new data have become apparent during the same time period when
      unprecedented numbers of physicians and medical staff have been exposed to
      unprecedented doses of scatter radiation as the number and complexity of
      fluoroscopic guided procedures has exploded. Increased rates of radiation lens
      damage have already been documented in physicians and support staff working in
      interventional medicine. As there is a latency period of years to decades for
      lens injury to fully evolve it is quite possible the true incidence will not be
      known for some time. Strategies to minimize the potential risks encountered in
      interventional medicine include radiation safety best practices, passive and
      personal barrier protection, and philosophical approach to interventional
      radiology practice. Ignore this article at your peril.

PMID- 29471997
TI  - Always on My Mind.
AB  - This article is focused on occupational radiogenic brain tumors and some
      radioprotective techniques used to manage this risk. Published case reports have
      stimulated concern among operators. The anatomical pattern of tumor locations is
      not consistent with measured radiation dose distributions at operators' heads. In
      addition, the lack of statistically positive findings in these reports, and a
      recently published survey on radiologist's mortality both indicate that the
      current level of fluoroscopists' radiation safety practices is likely to be
      adequate. This presumes that the rules of dose-management, time, distance, and
      shielding continue to be followed. These are briefly reviewed in this article.
      The use of radioprotective surgical caps is a current fashion. In clinical
      practice, these caps provide minimal reductions in brain dose and might induce
      operators to neglect applying the practical rules mentioned above. Appropriate
      management of personal, staff, and patient risk should always be on the
      radiologists' mind.

PMID- 29471998
TI  - Baby on Board: Managing Occupational Radiation Exposure During Pregnancy.
AB  - This article reviews the issue of occupational radiation exposure as a deterrent
      to recruitment of women into the field of interventional radiology and provides
      the reader with three strategies to optimize radiation protection during
      fluoroscopically guided procedures. These include personal protective shielding,
      use of ancillary shielding, and techniques that limit fluoroscopy x-ray tube
      output. When optimal radiation safety practices are implemented as the norm in
      the IR suite, very little extra needs to be done to ensure that fetal dose of a
      pregnant interventionalist is negligible.

PMID- 29471999
TI  - Make Radiation Protection a Habit.
AB  - This review describes the basic concepts and methods for optimization of
      occupational dose in the interventional suite. In fluoroscopy, the source of
      virtually all radiation exposure to the operator is scattered radiation from the
      patient. All other things being equal, reducing patient radiation dose will
      reduce operator and staff dose. Most tools and methods of occupational radiation
      protection are entirely operator dependent. These methods must be used routinely
      and properly to be effective. Your occupational dose depends on how well you
      follow good radiation protection practices and on the kinds of procedures you do.
      The only way to know your own occupational dose is to wear your dosimeters for
      every case. If proper protection practices are followed and appropriate
      protection tools are used, annual effective dose for an interventionalist should
      be well below 10mSv/y, and will more likely be in the range of 2-4mSv/y. However,
      if proper protection practices and tools are not used, annual effective doses may
      be much higher. You should review your own doses periodically.

PMID- 29472000
TI  - Get the Lead off Our Backs!
AB  - Many interventionalists face physical challenges almost daily for years or
      decades. The burden of assuming awkward positions while carrying extra weight can
      take its toll on the musculoskeletal system to such an extent that the career is
      ended or modified to exclude procedural aspects. The proliferation of lighter
      aprons has unfortunately resulted in reduced protection with poor correlation of
      protection to labeling due to the inadequacies of testing methods for nonlead
      materials. The protective quality of the non-leads is not superior to lead
      containing composites on a weight basis, and the user no longer knows how well
      they are protected unless buying aprons containing lead. Various useful methods
      and shields that may reduce radiation exposure are supported by the floor,
      ceiling, table, or patient. The suspended personal radiation protection system is
      a recent development which provides substantially greater radiation protection
      than conventional lead aprons combined with other shields, while also taking all
      of the weight off of the operator. It is composed of an expansive and thick (1mm
      Pb equiv) apron with a large face-shield to protect the neck, head, and eyes, and
      is suspended overhead to provide motion in the x, y, and z planes. Exposures may
      also be substantially reduced by leaving the area during acquisition sequences
      and use of power injectors.

PMID- 29472001
TI  - MACRA 2018 and the Virtual Group.

PMID- 29472002
TI  - Role of orexins in the central and peripheral regulation of glucose homeostasis:
      Evidences & mechanisms.
AB  - Orexins (A & B), neuropeptides of hypothalamic origin, act through G-protein
      coupled receptors, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). The
      wide projection of orexin neurons in the hypothalamic region allows them to
      interact with the other neurons and regulate food intake, emotional status, sleep
      wake cycle and energy metabolism. The autonomic nervous system plays an important
      regulatory role in the energy metabolism as well as glucose homeostasis. Orexin
      neurons are also under the control of GABAergic neurons. Emerging preclinical as
      well as clinical research has reported the role of orexins in the glucose
      homeostasis since orexins are involved in hypothalamic metabolism circuitry and
      also rely on sensing peripheral metabolic signals such as gut, adipose derived
      and pancreatic peptides. Apart from the hypothalamic origin, integration and
      control in various physiological functions, peripheral origin in wide organs,
      raises the possibility of use of orexins as a therapeutic biomarker in the
      management of metabolic disorders. The present review focuses the central as well
      as peripheral roles of orexins in the glucose homeostasis.

PMID- 29472003
TI  - Overcoming adversity-a critical step toward career satisfaction and leadership in
      academic surgery.
AB  - The experiences of life are what shape us. This article relays stories of
      adversity and resiliency as experienced and told by members of our own surgical
      community at the Academic Surgical Congress in Las Vegas, NV in February 2017. We
      aim to express in words the lessons of each experience so that others can learn
      about life and leadership.

PMID- 29472004
TI  - Diagnosis and Management of Stress-Induced Cardiomyopathy in Cancer Patients.

PMID- 29472005
TI  - Not All Electrocardiographic Variants in Black Patients Can be Considered
      "Normal".

PMID- 29472006
TI  - Is It Fair to Screen Only Competitive Athletes for Sudden Death Risk, or Is It
      Time to Level the Playing Field?

PMID- 29472007
TI  - Anticoagulant Agents for Atrial Fibrillation in Cancer Patients.

PMID- 29472008
TI  - Efficacy and Safety of Alirocumab in High-Risk Patients With Clinical
      Atherosclerotic Cardiovascular Disease and/or Heterozygous Familial
      Hypercholesterolemia (from 5 Placebo-Controlled ODYSSEY Trials).
AB  - Patients with previous atherosclerotic cardiovascular disease (ASCVD) and/or
      heterozygous familial hypercholesterolemia (HeFH) are at high risk of future
      cardiovascular events. Despite maximally tolerated doses of statins, many
      patients still have elevated low-density lipoprotein cholesterol (LDL-C) levels.
      We evaluated the efficacy and safety of alirocumab in patients with ASCVD and/or
      HeFH on a maximally tolerated dose of statin (rosuvastatin 20 or 40 mg,
      atorvastatin 40 or 80 mg, or simvastatin 80 mg, or lower doses with an
      investigator-approved reason) +/- other lipid-lowering therapies from 5 placebo
      controlled phase 3 trials (52 to 78 weeks). Patients with (n = 2,449) and without
      (n = 1,050) ASCVD were pooled from the FH I, FH II, HIGH FH, LONG TERM, and COMBO
      I trials. Patients with HeFH with (n = 575) and without ASCVD (n = 682) were
      pooled from all trials except COMBO I. High-intensity statins were utilized in
      55.7% to 59.0% and in 72.4% to 87.6% of the ASCVD and the HeFH groups,
      respectively. Efficacy end points included LDL-C percent change from baseline to
      week 24 stratified by alirocumab dose. Mean baseline demographics and lipid
      levels were comparable in alirocumab- and placebo-treated patients. LDL-C
      reductions from baseline at week 24 ranged from 46.6% to 51.3% for alirocumab
      75/150 mg and from 54.1% to 61.9% for alirocumab 150 mg in ASCVD and HeFH groups
      and were sustained for up to 78 weeks. LDL-C reductions with alirocumab were
      independent of ASCVD and/or HeFH status (interaction p value >0.05). Concordant
      results were observed for other lipids analyzed. The overall safety in the
      subgroups analyzed was similar in both treatment arms. Injection-site reactions
      were observed more frequently with alirocumab versus placebo.

PMID- 29472009
TI  - Long-Term Change in Cardiorespiratory Fitness in Relation to Atrial Fibrillation
      and Heart Failure (from the Kuopio Ischemic Heart Disease Risk Factor Study).
AB  - The benefits of aerobic fitness in relation to all-cause and cardiovascular
      mortality is well established; however, the associations of long-term change in
      cardiorespiratory fitness (CRF) with incident heart failure (HF) and atrial
      fibrillation (AF) have not been studied before. The Kuopio Ischaemic Heart
      Disease Risk Factor Study is a prospective cohort comprising men aged 42 to 60
      years from the city of Kuopio and its surroundings, with a baseline examination
      between 1984 and 1989 (V1), a re-examination at 11 years (V2), and up to 15 years
      of follow-up from V2. CRF, as assessed by VO2max, was measured at both visits
      using respiratory gas exchange during maximal exercise tolerance test. The
      difference (DeltaVO2max) was estimated as VO2max (V2) - VO2max (V1). Participants
      with no missing data on both baseline and 11-year exercise test were included (n
      = 481). The mean DeltaVO2max was -5.4 ml/min?kg (standard deviation 5.4). During
      a median follow-up of 14.3 years (interquartile range 13.3 to 15.1), 46 incident
      HF (9.6%) and 73 incident AF (15.2%) events were recorded. In a multivariate
      analysis adjusted for baseline age, baseline VO2max, systolic blood pressure,
      smoking, type 2 diabetes, and cardiovascular disease, per 1 ml/min?kg higher
      DeltaVO2max was log linearly associated with incident HF with a 10% relative risk
      reduction of HF (hazard ratio 0.90, 95% confidence interval 0.83 to 0.97). No
      significant relation of DeltaVO2max with incident AF was observed. In conclusion,
      overall long-term improvement in CRF is associated with reduced risk of HF,
      indicating the importance of maintaining good CRF over time.

PMID- 29472010
TI  - A little bit faster: Lower extremity joint kinematics and kinetics as
      recreational runners achieve faster speeds.
AB  - There appears a linear relationship between small increases in running speed and
      cardiovascular health benefits. Encouraging or coaching recreational runners to
      increase their running speed to derive these health benefits might be more
      effective if their joint level kinematic and kinetic strategy was understood. The
      aim of this investigation was to compare the peak sagittal plane motions,
      moments, and powers of the hip, knee and ankle at 85%, 100%, 115% and 130% of
      self-selected running speed. Overground running data were collected in 12
      recreational runners (6 women, 6 men) with a full body marker set using a 12
      camera Vicon MX system with an AMTI force plate. Kinematics and kinetics were
      analyzed with Vicon Nexus software. Participants chose to run at 2.6 +/- 0.5 m/s
      (85%); 3.0 +/- 0.5 m/s (100%); 3.3 +/- 0.5 m/s (115%); and 3.7 +/- 0.5 m/s
      (130%); these four speeds approximately correspond to 6:24-, 5:33-, 5:03-, and
      4:30-min kilometer running paces. Running speed had a significant effect (P <
      0.05) on peak kinematic and kinetic variables of the hips, knees and ankles, with
      peak sagittal hip moments invariant (P > 0.54) and the peak sagittal ankle power
      generation (P < 0.0001) the most highly responsive variable. The timing of the
      peak sagittal extensor moments and powers at the hip, knee and ankle were
      distributed across stance in a sequential manner. This study shows that running
      speed affects lower limb joint kinematics and kinetics and suggests that specific
      intersegmental kinetic strategies might exist across the narrow range of running
      speeds.

PMID- 29472011
TI  - Chemokine regulation of innate lymphoid cell tissue distribution and function.
AB  - Three groups of innate lymphoid cells (ILCs) can be defined based on
      transcription factor requirements, cytokine production profiles, and roles in
      immunity. Given their strategic anatomical location into barrier tissues and the
      ability to rapidly produce cytokines and to cross-talk with other immune and non
      immune cells, ILCs play fundamental functions in tissue homeostasis and
      regulation of immune responses. Several members of the chemokine family influence
      ILC tissue localization in the correct microenvironment by regulating their
      release from the bone marrow as well as their homing and retention in the
      tissues. In this review, we discuss the recent advances on how chemokine
      regulation of ILC tissue-positioning and functional interaction with other cells
      play essential roles in tissue-specific regulation of innate and adaptive immune
      responses.

PMID- 29472012
TI  - Prioritising recommendations to advance community pharmacy practice.
AB  - INTRODUCTION: The nature of community pharmacy in many countries has changed.
      Despite the significant efforts made to change practice, there is a paucity of
      literature that highlights consensus on the approaches that should be prioritised
      for advancing practice particularly in the context of developing countries.
      OBJECTIVE: To systematically identify and prioritise a range of potential
      recommendations to improve practice in Indonesian community pharmacy from the
      perspective of pharmacy stakeholders. METHODS: Qualitative research using Nominal
      Group Technique (NGT) was conducted in July 2017 involving 34 nationwide pharmacy
      stakeholders. Participants were assigned to four nominal group discussions based
      on the areas for action as developed by researchers. The results were
      thematically analysed. RESULTS: Nine priority recommendations were generated from
      the group discussion reflecting four main themes to advance community pharmacy
      sector, namely improving professional pharmacy practice, reforming pharmacy
      education, enforcing policy and regulation and enhancing public recognition of
      pharmacists. The analysis using the culture-structure-agency approach highlights
      that the top down structure in terms of policy and regulatory framework has not
      been effectively enforced. In addition, the role of pharmacists as the central
      agency in delivering pharmacy services has been limited due to their common
      absence from practice. The approach, however, provides an alternative to advocate
      changes by locating the role of pharmacists and community pharmacy as central
      agency within the challenging health system structure. CONCLUSIONS: The
      recommendations generated from and approach used in this study provide an impetus
      to advance community pharmacy practice in Indonesia. Amongst the important
      solutions, there is substantial need to provide evidence of pharmacists'
      contribution to healthcare.

PMID- 29472013
TI  - Using Technology in Global Otolaryngology.
AB  - Technology is integral to the diverse diagnostics and interventions of
      Otolaryngology. Historically, major advances in this field derive from advances
      of associated technologies. Challenges of visualization and surgical access are
      increasingly overcome by integrating endoscopic, electronic, and robotic
      instruments. Otolaryngology is often limited to urban areas and large academic
      centers, making it difficult to allocate care and resources to many underserved
      populations. The widespread use of technology has important implications in
      regards to global access to this field as telemedicine is most effectively
      applied to specialties that are heavily reliant on data and visuals that may be
      electronically disseminated.

PMID- 29472014
TI  - Imaging diagnosis of portal hypertension.
AB  - Portal hypertension is a clinical entity defined by a hydrostatic pressure
      greater than 5mm Hg in the portal territory, being clinically significant when it
      is greater than or equal to 10mm Hg. Starting from this threshold, complications
      can develop, such as the bleeding of esophageal varices, the appearance of
      ascites, or hepatic encephalopathy. Imaging techniques play an important role as
      a noninvasive method for determining whether portal hypertension is present. This
      article analyzes various imaging findings that can suggest the presence of portal
      hypertension and can help to define its etiology, severity, and possible
      complications.

PMID- 29472015
TI  - [What is the cost of treatment of diabetic retinopathy by argon laser in
      Yaounde?]
AB  - PURPOSE: To evaluate the total cost of treatment of diabetic retinopathy by argon
      laser for a patient when indicated. PATIENTS AND METHOD: Prospective cross
      sectional and descriptive survey, carried out in the angiography and laser center
      of the Yaounde Central Hospital from October 2014 to October 2015. All
      consecutive diabetic patients with retinopathy and suitable indication for argon
      laser treatment were included. The costs related to the initial and final
      fluorescein angiography, the appointment for follow-up, round-trip transportation
      costs from the patient's home and the cost of laser treatment were included.
      RESULTS: Included were 43 (13 %) patients out of 330 with diabetic retinopathy.
      The mean age was 55.67+/-8.40years. There were 25 women (58.1 %) and 18 men (41.9
      %) for a M/F ratio of 0.7. Unemployed patients were represented by 28 (65.1 %)
      versus 15 employed (34.9 %). Twenty-seven patients (62.8 %) were self-pay for all
      their expenses, 14 (32.6 %) were assisted by their families, and 2 (4.6 %) were
      insured. On average, the total expenditure was 86002+/-67197 f CFA per eye,
      corresponding to 131+/-102 euros with an exchange rate of 1 euro for 656 f CFA.
      CONCLUSION: The cost of treatment of diabetic retinopathy by argon laser is high,
      mostly increased by the additional costs related to transportation in our area.
      The creation of satellite centers in the 10 regions of Cameroon would reduce
      these costs.

PMID- 29472016
TI  - Opioid use in gynecologic oncology in the age of the opioid epidemic: Part I -
      Effective opioid use across clinical settings, a society of gynecologic oncology
      evidence-based review.
AB  - As the only oncologists that provide both medical and surgical oncologic care,
      gynecologic oncologists encounter an exceptionally broad range of indications for
      prescribing opioids, from management of acute post-operative pain to chronic
      cancer-related pain to end-of-life care. If we are to balance opioid efficacy,
      safety and accessibility for our patients, we must be intimately familiar with
      appropriate clinical use of opioids in a range of settings, and engage in the
      national conversation around opioid misuse and how associated regulations and
      legislation may impact us and our patients. This article examines the appropriate
      use of opioids across the range of clinical settings encountered in gynecologic
      oncology.

PMID- 29472017
TI  - Rethinking tuberculosis control by targeting previously treated individuals.

PMID- 29472019
TI  - Dynamics of serum C-type natriuretic peptide as predictor for preeclampsia.
AB  - OBJECTIVE: To evaluate serum levels of the amino-terminal propeptide of C-type
      natriuretic peptide (NTproCNP) in uneventful pregnancies and pregnancies
      complicated by preeclampsia (PE) and NTproCNP's accuracy for prediction of PE.
      STUDY DESIGN: Nested case control pilot study including women with uneventful
      pregnancy (Control, n = 100) and asymptomatic women who later developed PE
      (PE_long, n = 12). NTproCNP levels were measured in a maximum of ten sequential
      blood samples per patient (seven visits during pregnancy, three afterwards),
      which had been collected prospectively. RESULTS: In controls, NTproCNP decreased
      from weeks 11-13 on, reaching a nadir at the end of the second trimester (weeks
      23-27), and subsequently reached the highest levels at the end of pregnancy. In
      comparison, the PE_long group showed a significantly different NTproCNP course (p
      = .042), including significantly elevated levels in weeks 18-22 (p = .034) and 23
      27 (p = .016). Significant predictive power of single time point measurements of
      NTproCNP for predicting short-term occurrence of preeclampsia in asymptomatic
      women was found in weeks 28-32 (p = .023) and 33-36 (p = .014). Furthermore, an
      increase > -0.038 pmol/l per week between weeks 11-13 and 14-17 was also
      predictive for PE (area under the curve, AUC: 0.75; p < .001; sensitivity: 90%;
      specificity: 60%), as was an increase of > 0.084 pmol/l per week between weeks 11
      13 and 18-22 (AUC: 0.69, p = .048; sensitivity: 55%; specificity: 88%).
      CONCLUSIONS: Measurement of NTproCNP in pregnancy might be useful to increase
      diagnostic awareness in women who will develop PE.

PMID- 29472018
TI  - Tuberculosis control interventions targeted to previously treated people in a
      high-incidence setting: a modelling study.
AB  - BACKGROUND: In high-incidence settings, recurrent disease among previously
      treated individuals contributes substantially to the burden of incident and
      prevalent tuberculosis. The extent to which interventions targeted to this high
      risk group can improve tuberculosis control has not been established. We aimed to
      project the population-level effect of control interventions targeted to
      individuals with a history of previous tuberculosis treatment in a high-incidence
      setting. METHODS: We developed a transmission-dynamic model of tuberculosis and
      HIV in a high-incidence setting with a population of roughly 40 000 people in
      suburban Cape Town, South Africa. The model was calibrated to data describing
      local demography, TB and HIV prevalence, TB case notifications and treatment
      outcomes using a Bayesian calibration approach. We projected the effect of annual
      targeted active case finding in all individuals who had previously completed
      tuberculosis treatment and targeted active case finding combined with lifelong
      secondary isoniazid preventive therapy. We estimated the effect of these targeted
      interventions on local tuberculosis incidence, prevalence, and mortality over a
      10 year period (2016-25). FINDINGS: We projected that, under current control
      efforts in this setting, the tuberculosis epidemic will remain in slow decline
      for at least the next decade. Additional interventions targeted to previously
      treated people could greatly accelerate these declines. We projected that annual
      targeted active case finding combined with secondary isoniazid preventive therapy
      in those who previously completed tuberculosis treatment would avert 40% (95%
      uncertainty interval [UI] 21-56) of incident tuberculosis cases and 41% (16-55)
      of tuberculosis deaths occurring between 2016 and 2025. INTERPRETATION: In this
      high-incidence setting, the use of targeted active case finding in combination
      with secondary isoniazid preventive therapy in previously treated individuals
      could accelerate decreases in tuberculosis morbidity and mortality. Studies to
      measure cost and resource implications are needed to establish the feasibility of
      this type of targeted approach for improving tuberculosis control in settings
      with high tuberculosis and HIV prevalence. FUNDING: National Institutes of
      Health, German Research Foundation.

PMID- 29472020
TI  - Sudden paraplegia due to spontaneous bleeding in a thoracic epidural angiolipoma
      and literature review.
AB  - BACKGROUND: Spinal angiolipomas are rare epidural tumours that are usually
      revealed by chronic symptoms of medullar irritation. We report a case of acute
      paraplegia caused by spontaneous bleeding revealing a thoracic angiolipoma. CASE
      DESCRIPTION: A 17-year-old male patient with no previous medical history was
      admitted for acute onset of paraplegia with bladder retention and loss of
      sensation in the lower limbs, preceded by dorsal pain during the three previous
      days. MRI showed an enhanced T1-weighted image of a T7-T12 epidural lesion. The
      T1-weighted isosignal and the T2-weighted hyposignal suggested haemorrhagic
      complications. Due to a mass effect on the spinal cord, an emergency laminectomy
      was performed. Histopathological examination of the lesion revealed an
      angiolipoma with spontaneous bleeding. Clinical outcome was favourable after two
      months. CONCLUSION: This case is one of the first to be reported, although the
      clinical presentation is similar to that of other rare reported cases of
      paraplegia due to spinal compression by tumoural bleeding.

PMID- 29472021
TI  - Burnout Syndrome: Global Medicine Volunteering as a Possible Treatment Strategy.
AB  - BACKGROUND: In the last few decades, "burnout syndrome" has become more common
      among clinicians, or at least more frequently recognized. Methods to prevent and
      treat burnout have had inconsistent results. Simultaneously, clinicians' interest
      in global medicine has increased dramatically, offering a possible intervention
      strategy for burnout while providing help to underserved areas. DISCUSSION:
      Caused by a variety of stressors, burnout syndrome ultimately results in
      physicians feeling that their work no longer embodies why they entered the
      medical field. This attitude harms clinicians, their patients and colleagues, and
      society. Few consistently successful interventions exist. At the same time,
      clinicians' interest in global medicine has risen exponentially. This paper
      reviews the basics of both phenomena and posits that global medicine experiences,
      although greatly assisting target populations, also may offer a strategy for
      combating burnout by reconnecting physicians with their love of the profession.
      CONCLUSIONS: Because studies have shown that regular volunteering improves mental
      health, short-term global medicine experiences may reinvigorate and reengage
      clinicians on the verge of, or suffering from, persistent burnout syndrome.
      Fortuitously, this intervention often will greatly benefit medically underserved
      populations.

PMID- 29472022
TI  - Is food protein induced enterocolitis syndrome only a non IgE-mediated food
      allergy?
AB  - Food protein induced enterocolitis syndrome (FPIES) is classified as non-IgE
      mediated or cell-mediated food allergy, although there is an atypical phenotype
      so defined for the presence of specific IgEs. All diagnostic criteria for FPIES
      include the absence of skin or respiratory symptoms of IgE-mediated type. We
      present four cases that suggest that specific IgEs may have a pathogenic role,
      resulting in the existence of different FPIES phenotypes. This could be important
      from a diagnostic and therapeutic point of view.

PMID- 29472023
TI  - First Patient With Salla Disease Confirmed by Genomic Analysis in Japan.

PMID- 29472024
TI  - Evaluation of the relationship between ventricular end-diastolic pressure and
      echocardiographic measures of diastolic function in adults with a Fontan
      circulation.
AB  - BACKGROUND: Echocardiographic assessment of diastolic function in the setting of
      Fontan physiology is not well validated. We recently demonstrated that
      atrioventricular systolic to diastolic duration ratio (AVV S/D ratio)
      independently predicts mortality in Fontan-adults and that a value >1.1 was
      associated with poor prognosis. PURPOSE: To correlate echocardiographic measures
      of diastolic function with direct measurement of ventricular end-diastolic
      pressure (VEDP). METHODS: A retrospective analysis was undertaken of Fontan
      adults who had transthoracic echocardiography (TTE) within 12 months of direct
      measurement of VEDP during cardiac catheterisation. RESULTS: Fifteen Fontan
      adults (3 males, mean age 29 +/- 9 years) were evaluated. Thirteen patients had
      dominant morphologic left ventricle and 2 had morphologic right ventricle. Four
      had atriopulmonary connection and 11 had total cavopulmonary connection. Twelve
      patients were NYHA Class I/II and 3 were Class III. Time between TTE and cardiac
      catheter was 46 +/- 113 days; VEDP was 8 +/- 5 mmHg. Ten patients had preserved
      ventricular function, 3 had mild and 2 had moderate systolic impairment by
      subjective TTE assessment. AVV S/D ratio had the strongest correlation with VEDP
      (r = 0.8, p = 0.001). AVV S/D ratio >= 1.1 had 100% positive predictive value and
      92% negative predictive value for detecting VEDP >10 mmHg. The only conventional
      echocardiographic measure of diastolic function that correlated with VEDP was
      pulmonary vein A wave - atrioventricular A wave duration difference (r = 0.8, p =
      0.02). CONCLUSIONS: TTE measures reflect VEDP in adults with a Fontan
      circulation. AVV S/D ratio is a simple parameter yet to enter standard practice
      that can be used to identify elevated VEDP.

PMID- 29472025
TI  - Aortic stenosis and aortic regurgitation express different titin isoforms:
      Differences and relationships with functional and geometric characteristics.
AB  - Background-Titin represents an important biomechanical sensor which determines
      compliance and diastolic/systolic function of the left ventricle (LV). To assess
      the different titin-isoform expression and the relationships with functional and
      geometric patterns, we analyzed titin-isoform expression and cardiomyocytes
      contractile function in myocardial biopsy samples of patients undergoing aortic
      valve replacement (AVR) for aortic stenosis (AS) and for aortic regurgitation
      (AR). Method -Specimens, collected from the LV of 35 with AS and 35 with AR
      undergoing AVR were analyzed for titin-isoform expression and cardiomyocytes
      force measurement. Ten donor hearts were analyzed as controls for normal values.
      Results were implemented with preoperative geometry and function assessed by
      Doppler echocardiography. Results-Compared to controls, N2BA/N2B titin-isoforms
      ratio was reduced to 0.24 in AS (p < 0.001) but increased to 0.51 in AR (p <
      0.001). N2BA/N2B titin-isoforms ratio was further reduced in 8 patients with
      severe (restrictive) diastolic dysfunction (0.17 +/- 0.03, p < 0.001) but was
      increased in patients with severe systolic dysfunction (0.58 +/- 0.07, p <
      0.001). As compared to controls, Fpasive was higher in AS (6.7 +/- 0.2 vs 4.4 +/-
      0.4 kN/m2, p < 0.001) but was lower in AR (3.7 +/- 0.2 vs 4.4 +/- 0.4 kN/m2, p <
      0.001). Total force was comparable. Fpassive was significantly higher in AS
      patients with severe than with moderate LV diastolic dysfunction (7.1 +/- 0.5 vs
      6.6. +/- 0.6, p = 0.004). Conclusions-titin-isoform expression differs in AS and
      AR as adaptive response to different pathophysiologic scenarios. Co-expressing
      isoforms at varying ratios results in modulation of the passive mechanical
      behavior of the LV at different degree of dysfunction and allows for compensative
      adjustment of the diastolic/systolic properties of the myocardium.

PMID- 29472026
TI  - Trends in the prevalence of metabolic syndrome and its components in the United
      States 2007-2014.
AB  - BACKGROUND: Recent trends in the prevalence of metabolic syndrome (MetS) and its
      components among U.S. adults are not known. METHODS: We performed an updated
      analysis using the National Health and Nutrition Examination Survey 2007-2014
      data to investigate the latest trends of prevalence of MetS and its components.
      MetS was defined based on the modified National Cholesterol Education Program
      Adult Treatment Panel III criteria. Multiple regression models were used to
      assess linear trends over the years, after adjusting for sex, age, and
      race/ethnicity, as appropriate. Sampling weights were considered to account for
      complex sampling design, and all estimates were adjusted by age by a direct
      method. RESULTS: During 2007-2014, the age-adjusted weighted prevalence (+/
      standard error) of MetS among U.S. adults was 34.3 +/- 0.8%. In age-stratified
      analysis, 54.9 +/- 1.7% of elderly population aged 60 and over had MetS. When
      evaluating trends from 2007 to 2014, the prevalence of MetS remained stable in
      all sex, age, and race/ethnicity groups (P-trends > 0.100 for all). Among the
      components of MetS, the prevalence of hypertriglyceridemia and fasting
      hyperglycemia decreased (P-trend <0.050). However, the prevalence of abdominal
      obesity significantly increased, especially in women (P-trend = 0.009). The
      prevalence of elevated blood pressure and low high-density lipoprotein
      cholesterol level remained stable. CONCLUSIONS: The prevalence of MetS remained
      stable during 2007-2014. However, it was still prevalent in the U.S., especially
      among the elderly population. The prevalence of abdominal obesity continued to
      increase in women for which more efforts should be made.

PMID- 29472027
TI  - Quantified degree of eccentricity of aortic valve calcification predicts risk of
      paravalvular regurgitation and response to balloon post-dilation after self
      expandable transcatheter aortic valve replacement.
AB  - BACKGROUND: Limited data exist regarding the impact of aortic valve calcification
      (AVC) eccentricity on the risk of paravalvular regurgitation (PVR) and response
      to balloon post-dilation (BPD) after transcatheter aortic valve replacement
      (TAVR). We investigated the prognostic value of AVC eccentricity in predicting
      the risk of PVR and response to BPD in patients undergoing TAVR. METHODS: We
      analyzed 85 patients with severe aortic stenosis who underwent self-expandable
      TAVR (43 women; 77.2+/-7.1years). AVC was quantified as the total amount of
      calcification (total AVC load) and as the eccentricity of calcium (EoC) using
      calcium volume scoring with contrast computed tomography angiography (CTA). The
      EoC was defined as the maximum absolute difference in calcium volume scores
      between 2 adjacent sectors (bi-partition method) or between sectors based on
      leaflets (leaflet-based method). RESULTS: Total AVC load and bi-partition EoC,
      but not leaflet-based EoC, were significant predictors for the occurrence of
      >=moderate PVR, and bi-partition EoC had a better predictive value than total AVC
      load (area under the curve [AUC]=0.863 versus 0.760, p for difference=0.006). In
      multivariate analysis, bi-partition EoC was an independent predictor for the risk
      of >=moderate PVR regardless of perimeter oversizing index. The greater bi
      partition EoC was the only significant parameter to predict poor response to BPD
      (AUC=0.775, p=0.004). CONCLUSION: Pre-procedural assessment of AVC eccentricity
      using CTA as "bi-partition EoC" provides useful predictive information on the
      risk of significant PVR and response to BPD in patients undergoing TAVR with self
      expandable valves.

PMID- 29472028
TI  - Failure mode and bimodal restenosis of drug-coated balloon in femoropopliteal
      intervention.
AB  - BACKGROUND: Pattern of DCB restenosis and associated outcomes in facing complex
      femoropopliteal lesions remain uncertain. METHODS: Data were retrospectively
      collected from dual centers in Taiwan on patients who underwent treatment with
      DCBs for femoropopliteal lesions between 2013 and 2016. The restenosis pattern
      was categorized by the index-treated length. Clinical outcomes and time to DCB
      restenosis were retrospectively analyzed. Cox proportional hazards model
      identified restenosis predictors. RESULTS: We recruited a total of 164 patients
      (91 men; median age 73 years) into the final analysis. The mean lesion length was
      204.0 +/- 109.2 mm. Of them, 45% total occlusions, 28% severe calcification and
      15% in-stent restenosis were treated. Fifty-five patients have DCB restenosis (28
      focal and 27 diffuse-occlusive patterns) over a 55-month follow-up. The median
      restenosis time emerged as a bimodal pattern with a significant difference
      between the diffuse-occlusive and focal restenosis group (225 vs. 484 days, P =
      0.01). The 1-year patency rate after reintervention for DCB restenosis also was
      different between both restenosis group (29% vs. 65%, P = 0.017). The anticipated
      timing of escape for diffuse-occlusive or focal restenosis was 687 and 1068 days,
      respectively. Independent factors were lesion length (P = 0.049) for diffuse
      occlusive restenosis and lumen gain of the popliteal artery for focal restenosis
      (P = 0.034). CONCLUSIONS: This study demonstrated time to DCB failure emerged as
      a bimodal pattern of distribution and associations of restenosis pattern to
      subsequent outcomes after the repeated intervention. Exemption from late catchup
      restenosis required 3-year observation instead of the 1-year mark for
      conventional treatment.

PMID- 29472029
TI  - Diets containing salmon fillet delay development of high blood pressure and
      hyperfusion damage in kidneys in obese Zucker fa/fa rats.
AB  - Hypertension is the leading risk factor for cardiovascular and chronic renal
      diseases, affecting more than 1 billion people. Fish intake is inversely
      correlated with the prevalence of hypertension in several, but not all, studies,
      and intake of fish oil and fish proteins has shown promising potential to delay
      development of high blood pressure in rats. The effects of baked and raw salmon
      fillet intake on blood pressure and renal function were investigated in obese
      Zucker fa/fa rats, which spontaneously develop hypertension with proteinuria and
      renal failure. Rats were fed diets containing baked or raw salmon fillet in an
      amount corresponding to 25% of total protein from salmon and 75% of protein from
      casein, or casein as the sole protein source (control group) for 4 weeks. Results
      show lower blood pressure and lower urine concentrations of albumin and cystatin
      C (relative to creatinine) in salmon diet groups when compared to control group.
      Morphological examinations revealed less prominent hyperfusion damage in
      podocytes from rats fed diets containing baked or raw salmon when compared to
      control rats. In conclusion, diets containing baked or raw salmon fillet delayed
      the development of hypertension and protected against podocyte damage in obese
      Zucker fa/fa rats.

PMID- 29472030
TI  - A randomized controlled trial comparing home-based isometric handgrip exercise
      versus endurance training for blood pressure management.
AB  - Aerobic endurance exercise (AEX) is an effective treatment in the prevention and
      management of high blood pressure (BP). Growing evidence suggests potential
      benefits from isometric handgrip (IHG) exercise, which may promote similar or
      even larger reductions in BP than AEX. We compared the effects of home-based AEX
      and home-based IHG on BP. Sixty healthy individuals (31 men; mean age, 33.1
      years; mean BP, 126.9 +/- 1.6/84.7 +/- 1.1 mm Hg) were randomized to IHG, AEX, or
      a control group. Both exercise interventions were performed in the home
      environment. The IHG group performed daily 4 * 2 minutes sustained grips at 30%
      of maximal volitional contraction. Participants in the AEX group were advised to
      perform at least 150 min/wk of aerobic exercise at moderate intensity. Outcome
      measurements were assessed at baseline and 8 weeks of follow-up. Compared with
      the control group, AEX resulted in a larger reduction in ambulatory BP; both AEX
      and IHG exercise tended to induce larger reductions in office systolic BP, and
      office diastolic BP was significantly more reduced after AEX but not IHG
      exercise. Responses to training were not significantly different between both the
      exercise interventions. Eight weeks of home-based AEX results in significant
      reductions in both ambulatory BP and office BP in healthy adults, whereas IHG
      reduces only office BP.

PMID- 29472031
TI  - Preoperative MR imaging for ESMO-ESGO-ESTRO classification of endometrial cancer.
AB  - OBJECTIVE: To retrospectively investigate whether magnetic resonance imaging
      (MRI) findings could contribute to predict histologic type, tumor grade and
      lymphovascular space invasion (LVSI) to improve preoperative assessment of
      endometrial cancer using the European Society for Medical Oncology (ESMO)
      European Society for Radiotherapy & Oncology (ESTRO) and European Society of
      Gynecological Oncology (ESGO) classification. METHODS: Between January 2008 and
      August 2014, 104 women (mean age, 65+/-11 [SD] years; range, 32-84 years) with
      International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial
      cancer underwent preoperative MRI of the pelvis. Two independent readers
      evaluated tumor heterogeneity and measured tumor size on T2-weighted, diffusion
      weighted and T1-weighted images obtained after gadolinium chelate administration
      at 2minutes. The apparent diffusion coefficient (ADC) was generated from pixel
      ADC from the whole tumor volume. RESULTS: A short axis>24mm on MRI was associated
      with histopathologic type 2, grade 3 tumor and presence of LVSI (P<0.01). There
      were no significant differences in minimum, mean and maximum ADC between
      presence/absence of LVSI. In 9.1% women (9/99), the accuracy of the ESMO-ESGO
      ESTRO classification with the inclusion of the MRI short-axis criterion was
      higher than that of the conventional ESMO classification to predict high-risk
      recurrence endometrial cancer (P=0.02). CONCLUSION: Tumor size reflects
      histologic type, tumor grade and LVSI in endometrial cancer. FIGO stage 1
      endometrial cancer>24mm should be classified preoperatively in the high
      intermediate or high-risk recurrence risk groups.

PMID- 29472032
TI  - Xanthogranulomatous pyelonephritis complicating crizotinib treatment of an ALK
      rearranged non-small-cell lung cancer.

PMID- 29472033
TI  - Impact of ocean acidification and warming on the productivity of a rock pool
      community.
AB  - This study examined experimentally the combined effect of ocean acidification and
      warming on the productivity of rock pool multi-specific assemblages, composed of
      coralline algae, fleshy algae, and grazers. Natural rock pool communities
      experience high environmental fluctuations. This may confer physiological
      advantage to rock pool communities when facing predicted acidification and
      warming. The effect of ocean acidification and warming have been assessed at both
      individual and assemblage level to examine the importance of species interactions
      in the response of assemblages. We hypothesized that rock pool assemblages have
      physiological advantage when facing predicted ocean acidification and warming.
      Species exhibited species-specific responses to increased temperature and pCO2.
      Increased temperature and pCO2 have no effect on assemblage photosynthesis, which
      was mostly influenced by fleshy algal primary production. The response of
      coralline algae to ocean acidification and warming depended on the season, which
      evidenced the importance of physiological adaptations to their environment in
      their response to climate change. We suggest that rock pool assemblages are
      relatively robust to changes in temperature and pCO2, in terms of primary
      production.

PMID- 29472034
TI  - Contrasting impacts of light reduction on sediment biogeochemistry in deep- and
      shallow-water tropical seagrass assemblages (Green Island, Great Barrier Reef).
AB  - Seagrass meadows increasingly face reduced light availability as a consequence of
      coastal development, eutrophication, and climate-driven increases in rainfall
      leading to turbidity plumes. We examined the impact of reduced light on above
      ground seagrass biomass and sediment biogeochemistry in tropical shallow- (~2 m)
      and deep-water (~17 m) seagrass meadows (Green Island, Australia). Artificial
      shading (transmitting ~10-25% of incident solar irradiance) was applied to the
      shallow- and deep-water sites for up to two weeks. While above-ground biomass was
      unchanged, higher diffusive O2 uptake (DOU) rates, lower O2 penetration depths,
      and higher volume-specific O2 consumption (R) rates were found in seagrass
      vegetated sediments as compared to adjacent bare sand (control) areas at the
      shallow-water sites. In contrast, deep-water sediment characteristics did not
      differ between bare sand and vegetated sites. At the vegetated shallow-water
      site, shading resulted in significantly lower hydrogen sulphide (H2S) levels in
      the sediment. No shading effects were found on sediment biogeochemistry at the
      deep-water site. Overall, our results show that the sediment biogeochemistry of
      shallow-water (Halodule uninervis, Syringodium isoetifolium, Cymodocea rotundata
      and C. serrulata) and deep-water (Halophila decipiens) seagrass meadows with
      different species differ in response to reduced light. The light-driven dynamics
      of the sediment biogeochemistry at the shallow-water site could suggest the
      presence of a microbial consortium, which might be stimulated by
      photosynthetically produced exudates from the seagrass, which becomes limited due
      to lower seagrass photosynthesis under shaded conditions.

PMID- 29472035
TI  - An overview of the accumulation of microcystins in aquatic ecosystems.
AB  - Cyanotoxins produced by toxic cyanobacteria pose a major, worldwide environmental
      threat to freshwater ecosystems. Microcystins (MCs) are considered to be the most
      hazardous groups. Indeed, some of the largest aquatic ecosystems on the earth are
      being contaminated with MCs. Questions have arisen regarding their transfer and
      bioaccumulation in natural environment. This review summarizes the present state
      of knowledge regarding toxic cyanobacteria and MCs, with a specific focus on
      their distribution in different components of aquatic ecosystems. Their
      accumulation in water columns, aquatic animals, plants, and sediments is
      summarized. MCs have been contaminating all areas of the aquatic ecosystems. Of
      these, the water column was the most contaminated with MCs and served as an
      intermediate transmission substation. Via this route, MCs could enter to other
      stations such as sediment, animals, aquatic and terrestrial plants. Therefore,
      the use of water contaminated with MCs may induce food chain contaminations with
      considerable health risks.

PMID- 29472036
TI  - Lanthanum-doped silica xerogels for the removal of fluorides from waters.
AB  - The objective of this study was to determine the influence of different
      operational variables on fluoride (F-) removal from waters using lanthanum (La)
      doped silica xerogels and the mechanisms involved in this process. Accordingly,
      four xerogels were synthesized, one acting as blank (X-B), two doped with LaCl3
      and dried at different temperatures (X-LaCl and X-LaCl-M), and a fourth doped
      with La2O3 (X-LaO). The results show that fluorides are only removed when La
      doped xerogels are utilized. In addition, X-LaCl yielded the highest adsorption
      capacity, removing 28.44% of the initial fluoride concentration at a solution pH
      of 7. Chemical characterization of materials confirmed that fluoride removal from
      waters is due to the precipitation of LaF3 on the surface of La-doped xerogels.
      The presence of dissolved organic matter on the aqueous solution also reduce the
      removal capacity of La xerogels. Finally, analysis of the influence of solution
      pH revealed that the adsorption capacity of all xerogels was highest at a
      solution pH of 7.

PMID- 29472037
TI  - Misplacing V1 and V2 can have clinical consequences.
AB  - The precordial electrocardiogram (ECG) leads V1 and V2 are often misplaced. Such
      misplacement usually involves placing these leads too high on the chest. The
      resulting ECG may generate erroneous ECG patterns: e.g. incomplete right bundle
      branch block, anterior T wave inversion, septal Q waves, ST-segment elevation.
      These features may falsely suggest acute or old cardiac ischemia, pulmonary
      embolism, or a type-2 Brugada pattern. On rare occasion, conversely, high
      placement of V1 and V2 may reveal a true type-1 Brugada pattern. The emergency
      clinician needs to be aware of the possibility of lead misplacement, and should
      know how to suspect it based on unusual P wave morphology in V1 and V2.

PMID- 29472038
TI  - Prognostic performance of Emergency Severity Index (ESI) combined with qSOFA
      score.
AB  - OBJECTIVE: We conducted this study to investigate whether ESI combined with qSOFA
      score (ESI+qSOFA) predicts hospital outcome better than ESI alone in the
      emergency department (ED). METHODS: This was a retrospective study for patients
      aged over 15years who visited an ED of a tertiary referral hospital from January
      1st, 2015 to December 31st, 2015. We calculated and compared predictive
      performances of ESI alone and ESI+qSOFA for prespecified outcomes. The primary
      outcome was hospital mortality, and the secondary outcome was composite outcome
      of in-hospital mortality and ICU admission. We calculated in-hospital mortality
      rates by positive qSOFA in each subgroup divided according to ESI levels (1, 2,
      3, 4+5). RESULTS: 43,748 patients were enrolled. The area under receiver
      operating characteristics curves were higher in ESI+qSOFA than in ESI alone for
      both mortality and composite outcome (0.786 vs. 0.777, P<.001 for mortality;
      0.778 vs. 0.774, P<.001 for composite outcome). In each subgroup divided by ESI
      levels, patients with positive qSOFA had significantly higher in-hospital
      mortality rate compared to those with negative qSOFA (20.4% vs. 14.7%, P=.117 in
      ESI level 1 subgroup; 11.3% vs. 2.7%, P=.001 in ESI level 2 subgroup; 2.3% vs.
      0.4%, P<.001 in ESI level 3 subgroup; 0.0% vs. 0.0% in ESI level 4 or 5
      subgroup). CONCLUSION: The prognostic performance of ESI+qSOFA for in-hospital
      mortality was significantly higher than that of ESI alone. Within each subgroup,
      patients with positive qSOFA had higher in-hospital mortality compared to those
      with negative qSOFA.

PMID- 29472039
TI  - Safety of bolus-dose phenylephrine for hypotensive emergency department patients.
AB  - INTRODUCTION: Bolus-dose phenylephrine (BDPE) is routinely used to treat
      hypotension in the operating room. BDPE's fast onset of action and ability to be
      administered peripherally have prompted calls for its use in the Emergency
      Department (ED). There are few published data on the safety of BDPE use in the
      ED. Primary concerns include BDPE's potential to cause dangerous hypertension or
      reflex bradycardia. We hypothesize that BDPE is a safe short-term vasopressor
      choice for hypotensive ED patients. METHODS: We conducted a structured chart
      review for all patients who received BDPE from preloaded syringes over 42months.
      We defined an adverse event (AE) as sBP>180, dBP>110, or HR<50 within 30min of
      receiving BDPE. We defined a serious adverse event (SAE) as an AE with
      pharmacologic intervention to correct vital sign abnormality. We also compared
      mean arterial pressure (MAP), sBP, and dBP pre/post BDPE administration to assess
      effectiveness. We used a two-sample t-test to assess for differences between the
      mean delta MAP after low versus high-dose BDPE. RESULTS: We identified 181 cases
      of ED use. 147 cases had complete pre/post vital signs. We identified 5 AEs and
      no SAEs. Three patients developed sBP>180mmHg. The patients suffered no apparent
      harm. No patients had dBP>110. Two patients developed bradycardia post-drug. In
      both cases, MAP improved despite bradycardia. CONCLUSIONS: BDPE does not appear
      to cause reflex bradycardia or hypertension requiring intervention among
      hypotensive ED patients. The apparent safety of BDPE should be confirmed in
      prospective trials.

PMID- 29472040
TI  - Nasal cannula during noninvasive positive pressure ventilation: Combining
      preoxygenation with apneic oxygen.

PMID- 29472042
TI  - Identification of predictors for wound complications following preoperative or
      postoperative radiotherapy in extremity soft tissue sarcoma.
AB  - INTRODUCTION: In extremity soft tissue sarcoma (ESTS), external beam radiotherapy
      (EBRT) has been used in addition to limb-sparing surgery (LSS). This study aims
      to identify predictors for major wound complication (MWC) development following
      EBRT and LSS in ESTS. METHODS: This retrospective study includes ESTS patients
      treated with EBRT and LSS between 2005 and 2017. Two groups were formed; Group I
      included preoperatively irradiated patients, whereas Group II included patients
      who underwent postoperative EBRT. Multivariate logistic regression analyses were
      performed to create a prediction model for MWC development. RESULTS: One hundred
      twenty-seven patients were included, 58 patients (45.7%) in Group I and 69
      patients (54.3%) in Group II. Some differences in baseline characteristics were
      found between the groups, e.g. in tumor size and grade, histological subtype and
      total RT dose. Twenty-three patients (39.7%) in Group I and 14 patients (20.3%)
      in Group II developed a MWC (p = 0.02). Preoperative EBRT was identified as
      independent predictor for MWC development, OR 2.75 (95%CI 1.21-6.26), p = 0.02.
      Furthermore, a trend towards an increased MWC risk was shown for patients' age
      (OR 1.02 (0.99-1.04)), delayed wound closure (OR 3.20 (0.64-16.02)) and negative
      surgical margins (OR 2.26 (0.72-7.11)). The area under the curve (AUC) of the
      model was 0.68 (0.57-0.79). CONCLUSIONS: This study corroborates the increased
      MWC risk following preoperative EBRT in ESTS. It remains important to carefully
      weigh the MWC risk against the expected long-term functional outcome, and to
      consider the liberal use of primary plastic surgical reconstructions in an
      individualized multidisciplinary tumor board prior to treatment.

PMID- 29472043
TI  - Neoadjuvant and adjuvant strategies in retroperitoneal sarcoma.
AB  - Extended surgery remains the mainstay of treatment in retroperitoneal sarcoma,
      although conflicting data exist on the benefit of neoadjuvant and adjuvant
      therapies, particularly with regard to tumour grade and histological type.
      Experience of radiotherapy and chemotherapy in extremity soft tissue sarcoma can
      inform treatment strategies, however these data cannot be universally
      extrapolated to the retroperitoneum where disease biology and anatomical
      considerations are different. The present review sets a historical context before
      discussing recent evidence and on-going multi-centre trials in retroperitoneal
      sarcoma. Promising data on histologically- and molecularly-targeted chemotherapy
      are discussed and the need for centralisation of retroperitoneal sarcoma services
      in order to facilitate large international collaborative trials is emphasised.

PMID- 29472044
TI  - Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Summary of
      Recommendations.
AB  - Pulmonary hypertension is a hemodynamic disorder defined by abnormally high
      pulmonary artery pressure that can occur in numerous diseases and clinical
      situations. The causes of pulmonary hypertension are classified into 5 major
      groups: arterial, due to left heart disease, due to lung disease and/or
      hypoxemia, chronic thromboembolic, with unclear and/or multifactorial mechanisms.
      This is a brief summary of the Guidelines on the Diagnostic and Treatment of
      Pulmonary Hypertension of the Spanish Society of Pulmonology and Thoracic
      Surgery. These guidelines describe the current recommendations for the diagnosis
      and treatment of the different pulmonary hypertension groups.

PMID- 29472045
TI  - Dosimetric properties of alpha-Al2O3: Tm+PTFE phosphor.
AB  - A new alpha-Al2O3 doped with Tm3+ ions was obtained by combustion method; doped
      alpha-Al2O3 in the powder form was mixed with polytetrafluoroethylene resin
      (PTFE) to obtain dosimeters in pellet form, in order to be used as radiation
      dosimeter. The glow curve, linearity, lower detection limit, repeatability and
      fading, were studied. The kinetic parameters were determined by deconvolution
      method. Morphological characteristics were studied by low vacuum scanning
      electron microscopy and X-ray diffraction. Results showed that alpha-Al2O3+PTFE
      obtained is a promising material to radiation dosimetry.

PMID- 29472046
TI  - Functional range of motion in the metacarpophalangeal joints of the hand measured
      by single axis electric goniometers.
AB  - BACKGROUND: The functional range of motion (fROM) of the metacarpophalangeal
      (MCP) joints during the performance of activities of daily living (ADL) has not
      yet been established. This study aimed to determine the fROM of all five digits
      and verify the accuracy and reproducibility of dynamic angle measurement using a
      single-axis electric goniometer (EG) during ADL movements of the hand. METHODS:
      This was a cross-sectional study. In EG suitability testing, we first confirmed
      the angles of a three-dimensional calibration device 10 times, and then compared
      EG readings with those determined by tomosynthesis images. Next, we determined
      the fROM of the MCP joints by evaluating all five digits of the dominant hands of
      10 healthy adults performing 16 ADL. Intra-rater reproducibility of MCP joint
      data during task performance was assessed in two healthy adults. RESULTS: Static
      measurements of the triangular object showed variance to be within one degree in
      39 of 40 trials. Differences between angles measured by the EG and those depicted
      by radiograph were a range of plus or minus five degrees in 88 of 96 digits. The
      fROM values for the thumb and index, middle, ring, and little fingers were -7.5
      to 35.3, 10.6 to 67.8, 4.0 to 79.9, 3.0 to 83.9, and 2.9-91.4 degrees of flexion,
      respectively. Flexion angle in the fROM of the index finger was significantly
      smaller than those of the ring and little fingers. The flexion and extension
      angles of the thumb were significantly smaller than those of the four ulnar
      fingers. The intra-rater correlation coefficients of two participants were high
      at 0.94 and 0.93, respectively. CONCLUSIONS: The method adopted in this study
      exhibited excellent accuracy and reproducibility and was therefore considered
      suitable for the real-time establishment of fROM flexion-extension angles of the
      MCP joints for all five digits. Our data are useful as a target arc of motion in
      the treatment of MCP joint disease or injury.

PMID- 29472047
TI  - Prevalence estimation and familial tendency of common forefoot deformities in
      Turkey: A survey of 2662 adults.
AB  - OBJECTIVE: This survey was designed to evaluate the prevalence estimations of HV,
      bunionette, hammertoe as well as their relations to shoe wearing and also
      familial tendency, in Turkey. MATERIAL AND METHODS: Two thousand six hundred
      sixty two volunteers (1615 females and 1047 males) with a mean age of 34.15 +/-
      14.23 (range; 18 to 96) years were asked to answer the predetermined
      questionnaire between January and June, 2016. Hallux valgus, hammertoe and
      bunionette images were provided as references and every adult participant without
      any known forefoot problems or past forefoot surgery history was asked to rate
      his/her foot and to respond the questions about family history and shoe wearing
      habits. Responses were statistically analyzed. RESULTS: The prevalence
      estimations of hallux valgus, bunionette and hammertoe were calculated as 54.3%,
      13.8% and 8.9% and positive family history rates were 53.2%, 61.2% and 56.1%,
      respectively. All three deformities were more common in females than in males (p
      < 0.001). Nonetheless the older age group reported significantly higher
      prevalence rates for only HV (p < 0.001). Likewise, among the three deformities,
      females reported a higher rate of positive family history only in HV compared to
      men (p < 0.001). Constricting shoe wear was found to affect HV incidence in women
      (p < 0.001) and bunionette incidence in both sexes (p < 0.01). CONCLUSION: This
      study concludes that forefoot deformities are common with high familial tendency.
      Hence it is worthwhile to work on molecular genetics and this may enable the
      anticipation of forthcoming deformities in order to take early action in
      prevention, in nearly the half of the population.

PMID- 29472048
TI  - Oral lichen planus - Differential diagnoses, serum autoantibodies, hematinic
      deficiencies, and management.
AB  - Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease that
      occurs more frequently in middle-aged and elderly female patients. Previous
      studies indicate that OLP is a T-cell dysfunction-induced localized autoimmune
      disease. Clinically, six types of OLP, namely reticular, papular, plaque-like,
      atrophic/erosive, ulcerative, and bullous types, can be identified. OLP more
      commonly affects buccal mucosa, tongue, and gingiva. It always has a bilateral
      and symmetric distribution of the oral lesions. Plaque-like and atrophic/erosive
      OLP may be misdiagnosed as oral leukoplakia and oral erythroleukoplakia,
      respectively. Our previous study found serum autoantibodies in 195 (60.9%) of the
      320 OLP patients. Specific serum anti-nuclear, anti-smooth muscle, anti
      mitochondrial, gastric parietal cell, thyroglobulin, and thyroid microsomal
      autoantibodies are present in 28.1%, 8.4%, 1.6%, 26.3%, 21.3%, and 24.4% of 320
      OLP patients, respectively. Furthermore, we also discovered that 21.9%, 13.6%,
      7.1%, 0.3%, and 14.8% of 352 OLP patients have hemoglobin, iron, vitamin B12, and
      folic acid deficiencies, and abnormally high serum homocysteine level,
      respectively. Therefore, it is very important to examine the serum autoantibody,
      hematinic and homocysteine levels in OLP patients before starting the treatments
      for OLP patients. Because OLP is an immunologically-mediated disease,
      corticosteroids are the drugs of choice for treatment of OLP.

PMID- 29472041
TI  - Adherence to best practice consensus guidelines for implant-based breast
      reconstruction: Results from the iBRA national practice questionnaire survey.
AB  - INTRODUCTION: The 2008 National Mastectomy and Breast Reconstruction Audit
      demonstrated marked variation in the practice and outcomes of breast
      reconstruction in the UK. To standardise practice and improve outcomes for
      patients, the British professional associations developed best-practice
      guidelines with specific guidance for newer mesh-assisted implant-based
      techniques. We explored the degree of uptake of best-practice guidelines within
      units performing implant-based reconstruction (IBBR) as the first phase of the
      implant Breast Reconstruction Evaluation (iBRA) study. METHODS: A questionnaire
      developed by the iBRA Steering Group was completed by trainee and consultant
      leads at breast and plastic surgical units across the UK. Simple summary
      statistics were calculated for each survey item to assess compliance with current
      best-practice guidelines. RESULTS: 81 units from 79 NHS Trusts completed the
      questionnaire. Marked variation was observed in adherence to guidelines,
      especially those relating to clinical governance and infection prevention
      strategies. Less than half (n = 28, 47%) of units obtained local clinical
      governance board approval prior to offering new mesh-based techniques and
      prospective audit of the clinical, cosmetic and patient-reported outcomes of
      surgery was infrequent. Most units screened for methicillin-resistant
      staphylococcus aureus prior to surgery but fewer than 1 in 3 screened for
      methicillin-sensitive strains. Laminar-flow theatres (recommended for IBBR) were
      not widely-available with less than 1 in 5 units having regular access. Peri
      operative antibiotics were widely-used, but the type and duration were highly
      variable. CONCLUSIONS: The iBRA national practice questionnaire has demonstrated
      variation in reported practice and adherence to IBBR guidelines. High-quality
      evidence is urgently required to inform best practice.

PMID- 29472050
TI  - 2017-A Banner Year for Thoracic Oncology.

PMID- 29472049
TI  - Comprehensive geriatric assessment: Benefits and limitations.

PMID- 29472051
TI  - The PD-L1 Immunohistochemistry Biomarker: Two Steps Forward, One Step Back?

PMID- 29472052
TI  - Thymic Tumors: Revisiting Autoimmunity to Give a Chance to Immunotherapy.

PMID- 29472053
TI  - Role of Thoracic Surgeons in Lung Cancer Screening: Opportune Time for
      Involvement.

PMID- 29472054
TI  - EGFR-RAD51 Fusion: A Targetable Partnership Originated from the Tumor Evolution?

PMID- 29472055
TI  - Late-Onset Cholecystitis with Cholangitis after Avelumab Treatment in Non-Small
      Cell Lung Cancer.

PMID- 29472056
TI  - Response to Nivolumab as Salvage Therapy in a Patient with Thymic Carcinoma.

PMID- 29472057
TI  - Late-Onset Adrenal Insufficiency More Than 1 Year after Stopping Pembrolizumab.

PMID- 29472058
TI  - PD-L1 Expression in Small Cell Lung Cancer.

PMID- 29472059
TI  - Co-alteration of c-Met and ROS1 in Advanced NSCLC: ROS1 Wins.

PMID- 29472060
TI  - Reporting on Two Novel Fusions, DYSF-ALK and ITGAV-ALK, Coexisting in One Patient
      with Adenocarcinoma of Lung, Sensitive to Crizotinib.

PMID- 29472061
TI  - Concomitant Epidermal Growth Factor Receptor Mutation and EML4-ALK Fusion in a
      Patient with Multifocal Lung Adenocarcinomas.

PMID- 29472062
TI  - Computational modeling of the human auditory periphery: Auditory-nerve responses,
      evoked potentials and hearing loss.
AB  - Models of the human auditory periphery range from very basic functional
      descriptions of auditory filtering to detailed computational models of cochlear
      mechanics, inner-hair cell (IHC), auditory-nerve (AN) and brainstem signal
      processing. It is challenging to include detailed physiological descriptions of
      cellular components into human auditory models because single-cell data stems
      from invasive animal recordings while human reference data only exists in the
      form of population responses (e.g., otoacoustic emissions, auditory evoked
      potentials). To embed physiological models within a comprehensive human auditory
      periphery framework, it is important to capitalize on the success of basic
      functional models of hearing and render their descriptions more biophysical where
      possible. At the same time, comprehensive models should capture a variety of key
      auditory features, rather than fitting their parameters to a single reference
      dataset. In this study, we review and improve existing models of the IHC-AN
      complex by updating their equations and expressing their fitting parameters into
      biophysical quantities. The quality of the model framework for human auditory
      processing is evaluated using recorded auditory brainstem response (ABR) and
      envelope-following response (EFR) reference data from normal and hearing-impaired
      listeners. We present a model with 12 fitting parameters from the cochlea to the
      brainstem that can be rendered hearing impaired to simulate how cochlear gain
      loss and synaptopathy affect human population responses. The model description
      forms a compromise between capturing well-described single-unit IHC and AN
      properties and human population response features.

PMID- 29472063
TI  - Modified Yarham and Smith scores for pathogenicity assessment of mtDNA tRNA
      variants.

PMID- 29472064
TI  - Major postoperative complications compromise oncological outcomes of patients
      with intrahepatic cholangiocarcinoma after curative resection - A 13-year cohort
      in a tertiary center.
AB  - BACKGROUND/OBJECTIVE: Hepatectomy is the mainstay of curative treatment for
      intrahepatic cholangiocarcinoma (ICC). The relationship between postoperative
      complication and oncological outcome has not been defined. We aimed to elucidate
      the effect of postoperative complication on long-term survival of ICC patients
      after curative resection. METHODS: Data of consecutive patients who had curative
      resection for ICC at our hospital from 1991 to 2013 were reviewed. Patients with
      cholangiohepatocellular carcinoma, metastatic adenocarcinoma or Klaskin tumor
      were excluded. Clinicopathological data and postoperative events were extracted
      from database for survival analysis. RESULTS: There were 107 patients in our
      series. Their median age was 61 years. The median follow-up time was 24 months.
      The median tumor size was 6 cm. Major hepatectomy was required in 52.3% of them.
      The median operation time and blood loss was 439 minutes and 0.9L respectively.
      R0 resection was achieved in 88.8% of them. The median length of stay was 11
      days. The 30-day and 90-day mortality was 2.5% and 6.8% respectively. Major
      complications were found in 20.6% of them. Patients with postoperative
      complications had significantly inferior survival than patients without (3-yr DFS
      38% vs. 27%, P = 0.001; 3-yr overall: 51% vs. 27%, P < 0.001). Multivariable
      analysis showed that postoperative complication was an independent factor
      associated with disease-free survival (OR 1.9 95% C.I. 1.10-3.24, P = 0.021) and
      overall survival (OR 2.1, 95% C.I. 1.13-3.93, P = 0.018). CONCLUSION:
      Postoperative complication has a significant impact on ICC patients' long-term
      survival. Extra measures such as adjuvant chemotherapy should be considered for
      patients who develop major complications after surgery.

PMID- 29472065
TI  - Size- and site-dependent distribution of therapeutic proteins into thoracic
      lymph: Cover Story.

PMID- 29472066
TI  - Serum levels of irisin predict short-term outcomes in ischemic stroke.
AB  - OBJECTIVE: Irisin is a 112-amino acid peptide found in rat and human skeletal
      muscle after exercise. Previous studies had suggested that higher circulating
      irisin levels were associated with an increased risk of vascular atherosclerosis
      and cardiovascular diseases. In this study, we determined irisin levels in serum,
      and investigated their associations with functional outcomes in a 3-month follow
      up study in Chinese patients with first-ever acute ischemic stroke (AIS).
      METHODS: From September 2015 to December 2016, consecutive first-ever AIS
      patients admitted to the Department of Emergency of our hospital were identified.
      Serum irisin levels were measured at admission. Functional impairment was
      evaluated at discharge using the modified Rankin scale. The levels of irisin were
      expressed as median and interquartile ranges [IQR]. RESULTS: The irisin level was
      obtained in 324 patients (97.6%) with a median value of 291.2 ng/ml (IQR: 214.1
      404.2 ng/ml). There were significantly negative correlations between levels of
      irisin and NHISS (r = -0.272; P < 0.001) and BMI (r = -0.193; P = 0.003). A poor
      functional outcome was found in 99 patients (30.6%; 95%CI: 25.5-35.6%). The poor
      functional outcome distribution across the irisin quartiles ranged between 51.9%
      (first quartile: Q1) to 12.4% (fourth quartile: Q4). In a multivariate model
      using the Q1 of irisin vs. Q2-4 together with the clinical variables, the marker
      displayed prognostic information and increased risk of poor outcomes by 94% (OR
      for Q1, 1.94 [95% CI, 1.19-3.42]; P = 0.018) and mortality 66% (OR for Q1, 1.66
      [95% CI, 1.11-3.07]; P = 0.009). In addition, a model containing known risk
      factors plus irisin compared with a model containing known risk factors without
      irisin showed a greater discriminatory ability to predict poor outcomes (P =
      0.01) and mortality (P = 0.02). CONCLUSIONS: A low serum irisin level is a
      predictor of poor early functional outcome in ischemic stroke patients. The
      underlying mechanisms of these associations remain to be investigated.

PMID- 29472067
TI  - Neurophysiology of hearing in patients with mucopolysaccharidosis type IV.
AB  - BACKGROUND: Hearing impairment is a common problem in patients with
      mucopolysaccharidosis IV (MPS IV) throughout their life. Many of the adult
      patients with MPS IV exhibit permanent or severe hearing loss. However, there has
      been no systematic review of detailed audiological test results in MPS IV.
      MATERIALS AND METHODS: Fourteen individuals with MPS IV (13 MPS IVA and 1 MPS
      IVB; aged between 12 and 38 years old) participated in the current study. We
      obtained auditory neurophysiological responses (auditory brainstem responses and
      otoacoustic emissions test) in addition to pure-tone audiometry and middle ear
      function tests (tympanometry and acoustic reflexes). RESULTS: The results
      indicated various levels and types of hearing loss with abnormal
      neurophysiological responses even in those patients with MPS IVA with normal pure
      tone thresholds. We also found a strong relationship between height (short
      stature is an indicator of skeletal severity) and hearing sensitivity as well as
      a strong relationship between height and outer hair cell function in the inner
      ear (measured by otoacoustic emissions) among MPS IVA patients. CONCLUSION: The
      strong correlation between reduced height and hearing loss indicates that
      patients with severe skeletal dysplasia may be at higher risk of developing more
      severe hearing loss. More importantly, the spectrum of hearing disorders
      indicates that MPS IV patients should have annual neurophysiological hearing
      tests in addition to audiometric testing from an early age regardless of their
      skeletal severity to more carefully monitor disease progression.

PMID- 29472068
TI  - Childhood cardiorespiratory fitness, muscular fitness and adult measures of
      glucose homeostasis.
AB  - OBJECTIVES: To assess whether childhood cardiorespiratory fitness (CRF) and
      muscular fitness phenotypes (strength, power, endurance) predict adult glucose
      homeostasis measures. DESIGN: Prospective longitudinal study. METHODS: Study
      examining participants who had physical fitness measured in childhood (aged 7-15
      years) and who attended follow-up clinics approximately 20 years later and
      provided a fasting blood sample which was tested for glucose and insulin.
      Physical fitness measurements included muscular strength (right and left grip,
      shoulder flexion, shoulder and leg extension), power (standing long jump
      distance) and endurance (number of push-ups in 30s), and CRF (1.6km run
      duration). In adulthood, fasting glucose and insulin levels were used to derive
      glucose homeostasis measures of insulin resistance (HOMA2-IR) and beta cell
      function (HOMA2-beta). RESULTS: A standard deviation increase in childhood CRF or
      muscular strength (males) was associated with fasting glucose (CRF: beta=
      0.06mmol/L), fasting insulin (CRF: beta=-0.73mU/L; strength: beta=-0.40mU/L),
      HOMA2-IR (CRF: beta=-0.06; strength: beta=-0.05) and HOMA2-beta (CRF: beta=
      3.06%; strength: beta=-2.62%) in adulthood, independent of the alternative
      fitness phenotype (all p<0.01). Adjustment for childhood waist circumference
      reduced the effect by 17-35% for CRF and 0-15% for muscular strength (males) and
      statistical significance remained for all associations expect between CRF,
      fasting glucose and HOMA2-beta (p>0.06). CONCLUSIONS: CRF and muscular fitness in
      childhood were inversely associated with measures of fasting insulin, insulin
      resistance and beta cell function in adulthood. Childhood CRF and muscular
      fitness could both be potential independent targets for strategies to help reduce
      the development of adverse glucose homeostasis.

PMID- 29472069
TI  - Idiopathic thoracic spinal cord herniation.
AB  - Idiopathic spinal cord herniation represents an uncommon and unique diagnostic
      entity, most commonly affecting middle-aged individuals, with a nearly twofold
      female predilection. It most characteristically affects the mid-thoracic spine,
      with the herniation occurring ventrally or ventrolaterally. Clinical presentation
      is typically a slowly-progressive myelopathy, with Brown-Sequard syndrome
      occurring more frequently than spastic paraparesis. Diagnosis is made by imaging,
      with high-resolution or phase-contrast MR sequences and/or CT myelography.
      Treatment should be individualized, with options including conservative
      management with routine follow-up and surgical intervention. We review the
      literature on this interesting topic and report on, and present our technique
      for, operative reduction and repair of idiopathic spinal cord herniation in a 66
      year-old woman.

PMID- 29472070
TI  - Investigating the causes of low detectability of pesticides in fruits and
      vegetables analysed by high-performance liquid chromatography - Time-of-flight.
AB  - Because of the high number of possible pesticide residues and their chemical
      complexity, it is necessary to develop methods which cover a broad range of
      pesticides. In this work, a qualitative multi-screening method for pesticides was
      developed by use of HPLC-ESI-Q-TOF. 110 pesticides were chosen for the creation
      of a personal compound database and library (PCDL). The MassHunter Qualitative
      Analysis software from Agilent Technologies was used to identify the analytes.
      The software parameter settings were optimised to produce a low number of false
      positive as well as false negative results. The method was validated for 78
      selected pesticides. However, the validation criteria were not fulfilled for 45
      analytes. Due to this result, investigations were started to elucidate reasons
      for the low detectability. It could be demonstrated that the three main causes of
      the signal suppression were the co-eluting matrix (matrix effect), the low
      sensitivity of the analyte in standard solution and the fragmentation of the
      analyte in the ion source (in-source collision-induced dissociation). In this
      paper different examples are discussed showing that the impact of these three
      causes is different for each analyte. For example, it is possible that an analyte
      with low signal intensity and an intense fragmentation in the ion source is
      detectable in a difficult matrix, whereas an analyte with a high sensitivity and
      a low fragmentation is not detectable in a simple matrix. Additionally, it could
      be shown that in-source fragments are a helpful tool for an unambiguous
      identification.

PMID- 29472071
TI  - Prediction of collision cross section and retention time for broad scope
      screening in gradient reversed-phase liquid chromatography-ion mobility-high
      resolution accurate mass spectrometry.
AB  - Exact mass, retention time (RT), and collision cross section (CCS) are used as
      identification parameters in liquid chromatography coupled to ion mobility high
      resolution accurate mass spectrometry (LC-IM-HRMS). Targeted screening analyses
      are now more flexible and can be expanded for suspect and non-targeted screening.
      These allow for tentative identification of new compounds, and in-silico
      predicted reference values are used for improving confidence and filtering false
      positive identifications. In this work, predictions of both RT and CCS values are
      performed with machine learning using artificial neural networks (ANNs).
      Prediction was based on molecular descriptors, 827 RTs, and 357 CCS values from
      pharmaceuticals, drugs of abuse, and their metabolites. ANN models for the
      prediction of RT or CCS separately were examined, and the potential to predict
      both from a single model was investigated for the first time. The optimized
      combined RT-CCS model was a four-layered multi-layer perceptron ANN, and the 95th
      prediction error percentiles were within 2 min RT error and 5% relative CCS error
      for the external validation set (n = 36) and the full RT-CCS dataset (n = 357).
      88.6% (n = 733) of predicted RTs were within 2 min error for the full dataset.
      Overall, when using 2 min RT error and 5% relative CCS error, 91.9% (n = 328) of
      compounds were retained, while 99.4% (n = 355) were retained when using at least
      one of these thresholds. This combined prediction approach can therefore be
      useful for rapid suspect/non-targeted screening involving HRMS, and will support
      current workflows.

PMID- 29472072
TI  - Parallel loading and complete automation of a 3-step mAb purification process for
      multiple samples using a customized preparative chromatography instrument with
      networked pumps.
AB  - Advancement in high-throughput screening methods of novel therapeutic proteins
      for early stage research and development, specifically mAbs, have given mid-scale
      (milligram to gram scale) purification groups access to more of these molecules.
      The available purification technologies built to support mid-scale production was
      not efficient or versatile enough to keep up with this surge. To remedy this
      problem, we have designed and built a custom instrument using an AKTA Pure. This
      system enables parallel processing up to 5 samples and has the versatility to
      perform 1- to 3-step purification processes in a single queue. Furthermore, a
      unique purification scheme can be selected for each of the five samples in the
      queue. Overall processing time has reduced by 83% compared to manual, non
      parallel load methods. Here, we describe our novel approach and demonstrate the
      flexibility, speed and efficiency of the instrument.

PMID- 29472073
TI  - Positional uncertainty of vaginal cuff and feasibility of implementing portable
      bladder scanner in postoperative cervical cancer patients.
AB  - PURPOSE: To propose a geometrical margin for definition of the vaginal cuff PTV
      using only CT images of the full bladder (CTfull) in postoperative cervical
      cancer patients. METHODS: Twenty-nine operated cervical cancer patients underwent
      volumetric arc therapy with a bladder filling protocol. This study assessed
      bladder filling using a portable bladder scanner and cone-beam computed
      tomography (CBCT) during the entire treatment period. The measured bladder
      volumes with a BladderScan(r) were compared with the delineated volume on CBCT.
      Titanium clips in the vaginal cuff were analysed to assess geometrical
      uncertainty and the influence of rectal and bladder volume changes. RESULTS:
      BladderScan(r) showed good agreement with the delineated volume (R = 0.80). The
      volume changes in the bladder have a greater influence on the clip displacements
      than in the rectum. The 95th percentile of uncertainty of the clips in reference
      to CTfull in the right-left (RL), the superoinferior (SI), and the
      anteroposterior (AP) was 0.32, 0.65, and 1.15 cm, respectively. From this result
      and intra-fractional movements of the vaginal cuff reported by Haripotepornkul, a
      new geometrical margin was proposed for definition of the vaginal cuff planning
      target volume (PTV): 0.5, 0.9, and 1.4 cm in the RL, SI, and AP directions,
      respectively. CONCLUSIONS: A new geometrical margin was proposed for definition
      of the vaginal cuff PTV based on CTfull, which will be needless of empty bladder
      at the planning CT scan. This method allows patients to reduce the burden and
      efficient routine CT scans can be improved.

PMID- 29472074
TI  - Feasibility of using a dose-area product ratio as beam quality specifier for
      photon beams with small field sizes.
AB  - PURPOSE: To investigate the feasibility of using the ratio of dose-area product
      at 20 cm and 10 cm water depths (DAPR20,10) as a beam quality specifier for
      radiotherapy photon beams with field diameter below 2 cm. METHODS: Dose-area
      product was determined as the integral of absorbed dose to water (Dw) over a
      surface larger than the beam size. 6 MV and 10 MV photon beams with field
      diameters from 0.75 cm to 2 cm were considered. Monte Carlo (MC) simulations were
      performed to calculate energy-dependent dosimetric parameters and to study the
      DAPR20,10 properties. Aspects relevant to DAPR20,10 measurement were explored
      using large-area plane-parallel ionization chambers with different diameters.
      RESULTS: DAPR20,10 was nearly independent of field size in line with the small
      differences among the corresponding mean beam energies. Both MC and experimental
      results showed a dependence of DAPR20,10 on the measurement setup and the surface
      over which Dw is integrated. For a given setup, DAPR20,10 values obtained using
      ionization chambers with different air-cavity diameters agreed with one another
      within 0.4%, after the application of MC correction factors accounting for
      effects due to the chamber size. DAPR20,10 differences among the small field
      sizes were within 1% and sensitivity to the beam energy resulted similar to that
      of established beam quality specifiers based on the point measurement of Dw.
      CONCLUSIONS: For a specific measurement setup and integration area, DAPR20,10
      proved suitable to specify the beam quality of small photon beams for the
      selection of energy-dependent dosimetric parameters.

PMID- 29472075
TI  - A novel high-resolution 2D silicon array detector for small field dosimetry with
      FFF photon beams.
AB  - PURPOSE: Flattening filter free (FFF) beams are increasingly being considered for
      stereotactic radiotherapy (SRT). For the first time, the performance of a
      monolithic silicon array detector under 6 and 10 MV FFF beams was evaluated. The
      dosimeter, named "Octa" and designed by the Centre for Medical Radiation Physics
      (CMRP), was tested also under flattened beams for comparison. METHODS: Output
      factors (OFs), percentage depth-dose (PDD), dose profiles (DPs) and dose per
      pulse (DPP) dependence were investigated. Results were benchmarked against
      commercially available detectors for small field dosimetry. RESULTS: The
      dosimeter was shown to be a 'correction-free' silicon array detector for OFs and
      PDD measurements for all the beam qualities investigated. Measured OFs were
      accurate within 3% and PDD values within 2% compared against the benchmarks.
      Cross-plane, in-plane and diagonal DPs were measured simultaneously with high
      spatial resolution (0.3 mm) and real time read-out. A DPP dependence (24% at
      0.021 mGy/pulse relative to 0.278 mGy/pulse) was found and could be easily
      corrected for in the case of machine specific quality assurance applications.
      CONCLUSIONS: Results were consistent with those for monolithic silicon array
      detectors designed by the CMRP and previously characterized under flattened beams
      only, supporting the robustness of this technology for relative dosimetry for a
      wide range of beam qualities and dose per pulses. In contrast to its
      predecessors, the design of the Octa offers an exhaustive high-resolution 2D dose
      map characterization, making it a unique real-time radiation detector for small
      field dosimetry for field sizes up to 3 cm side.

PMID- 29472076
TI  - Robustness of VMAT and 3DCRT plans toward setup errors in radiation therapy of
      locally advanced left-sided breast cancer with DIBH.
AB  - PURPOSE: The aim of our study was to evaluate and compare the robustness of
      treatment plans produced using the volumetric modulated arc-therapy (VMAT) and
      the standard three-dimensional conformal radiotherapy (3DCRT) techniques by
      estimating perturbed doses induced by localization offsets for deep inspiration
      breath-hold (DIBH) in locally advanced breast cancer radiation therapy. METHODS:
      Twenty patients with left breast carcinoma requiring radiation therapy were
      analysed in this planning study. Robust VMAT plans regarding minimum CTV doses
      and standard 3DCRT plans were produced, and perturbed doses were calculated in
      accordance with localization values from the weekly offline imaging protocol.
      Offsets from 5 weeks were summed to a perturbed overall treatment plan. Dose
      criteria for evaluation were coverage and homogeneity of the target, as well as
      doses to organs at risk. RESULTS: VMAT plans resulted in significantly better
      target coverage compared to 3DCRT, as well as lowered doses to heart and left
      anterior descending artery, while the perturbed doses were less variable for VMAT
      than 3DCRT plans. Homogeneity was significantly improved in VMAT plans. The
      statistical analysis taking all organs into account found that VMAT plans were
      more robust than 3DCRT to localization offsets (p = .001). The overall mean setup
      deviation for the DIBH-patients was less than 2 mm in all directions.
      CONCLUSIONS: VMAT plans were more robust on average than conventional 3DCRT plans
      for DIBH when localization errors were taken into consideration. The combination
      of robust VMAT planning and DIBH generally improves the homogeneity and target
      doses.

PMID- 29472077
TI  - Evaluation of size, morphology, concentration, and surface effect of gold
      nanoparticles on X-ray attenuation in computed tomography.
AB  - Increasing attention has been focused on the use of nanostructures as contrast
      enhancement agents in medical imaging, especially in computed tomography (CT). To
      date, gold nanoparticles (GNPs) have been demonstrated to have great potential as
      contrast agents for CT imaging. This study was designed to evaluate any effect on
      X-ray attenuation that might result from employing GNPs with a variety of shapes,
      sizes, surface chemistries, and concentrations. Gold nanorods (GNRs) and
      spherical GNPs were synthesized for this application. X-ray attenuation was
      quantified by Hounsfield unit (HU) in CT. Our findings indicated that smaller
      spherical GNPs (13 nm) had higher X-ray attenuation than larger ones (60 nm) and
      GNRs with larger aspect ratio exhibited great effect on X-ray attenuation.
      Moreover, poly ethylene glycol (PEG) coating on GNRs declined X-ray attenuation
      as a result of limiting the aggregation of GNRs. We observed X-ray attenuation
      increased when mass concentration of GNPs was elevated. Overall, smaller
      spherical GNPs can be suggested as a better alternative to Omnipaque, a good
      contrast agent for CT imaging. This data can be also considered for the
      application of gold nanostructures in radiation dose enhancement where
      nanoparticles with high X-ray attenuation are applied.

PMID- 29472078
TI  - Intercomparison of 99mTc, 18F and 111In activity measurements with radionuclide
      calibrators in Belgian hospitals.
AB  - This study presents current status of performance of radiopharmaceutical activity
      measurements using radionuclide calibrators in Belgium. An intercomparison
      exercise was performed among 15 hospitals to test the accuracy of 99mTc, 18F and
      111In activity measurements by means of radionuclide calibrators. Four sessions
      were held in different geographical regions between December 2013 and February
      2015. The data set includes measurements from 38 calibrators, yielding 36
      calibrations for 99mTc and 111In, and 21 calibrations for 18F. For each
      radionuclide, 3 ml of stock solution was measured in two clinical geometries: a
      10 ml glass vial and a 10 ml syringe. The initial activity was typically 100 MBq
      for 99mTc, 15 MBq for 111In and 115 MBq for 18F. The reference value for the
      massic activity of the radioactive solutions was determined by means of primary
      and secondary standardisation techniques at the radionuclide metrology laboratory
      of the JRC. The overall results of the intercomparison were satisfactory for
      99mTc and 18F, since most radionuclide calibrators (>70%) were accurate within +/
      5% of the reference value. Nevertheless, some devices underestimated the activity
      by 10-20%. Conversely, 111In measurements were strongly affected by source
      geometry effects and this had a negative impact on the accuracy of the
      measurements, in particular for the syringe sample. Large overestimations (up to
      72%) were observed, even when taking into account the corrections and
      uncertainties supplied by the manufacturers for container effects. The results of
      this exercise encourage the hospitals to perform corrective actions to improve
      the calibration of their devices where needed.

PMID- 29472079
TI  - Thermoluminescence dosimetry of the dose received by scrotum and testes in
      radiotherapy of rectal cancer, compared to the point doses calculated by 3D
      planning software.
AB  - PURPOSE: Radiation received by the testes in the course of radiotherapy for
      rectal cancer may cause oligospermia and azospermia. We sought to determine the
      dose to the scrotum and testes with thermoluminescence dosimetry (TLD), and
      compare it to the dose calculated by 3D planning software. METHODS: The TLDs were
      fixed to the scrotum in six points anteriorly and posteriorly in two fractions of
      radiotherapy. All patients received a 50-50.4 Gy total dose in prone position
      with 3D-planning. The average dose of TLD measurements was compared to the
      average of 6 relevant point doses calculated by the planning software. RESULTS:
      The mean scrotal dose of radiation in 33 patients as measured by TLD was 3.77 Gy
      (7.5% of the total prescribed dose), and the mean of point doses calculated by
      the planning software was 4.11 Gy (8.1% of the total dose), with no significant
      difference. A significant relationship was seen between the position of the
      inferior edge of the fields and the mean scrotal dose (P = .04). Also body mass
      index (BMI) was inversely related with the scrotal dose (P = .049). CONCLUSION:
      We found a dose of about 4 Gy received by the scrotum and testes from a total
      prescribed dose of 50 Gy in the radiotherapy of rectal carcinoma patients, with
      TLD measurements confirming testicular dose estimations by the planning software.
      This dose could be significantly harmful for spermatogenesis. Thus careful
      attention to the testicular dose in radiotherapy of rectal cancer for men
      desiring continued fertility is a necessity.

PMID- 29472081
TI  - Experimental optimisation of the X-ray energy in microbeam radiation therapy.
AB  - Microbeam radiation therapy has demonstrated superior normal tissue sparing
      properties compared to broadbeam radiation fields. The ratio of the microbeam
      peak dose to the valley dose (PVDR), which is dependent on the X-ray
      energy/spectrum and geometry, should be maximised for an optimal therapeutic
      ratio. Simulation studies in the literature report the optimal energy for MRT
      based on the PVDR. However, most of these studies have considered different
      microbeam geometries to that at the Imaging and Medical Beamline (50 MUm beam
      width with a spacing of 400 MUm). We present the first fully experimental
      investigation of the energy dependence of PVDR and microbeam penumbra. Using
      monochromatic X-ray energies in the range 40-120 keV the PVDR was shown to
      increase with increasing energy up to 100 keV before plateauing. PVDRs measured
      for pink beams were consistently higher than those for monochromatic energies
      similar or equivalent to the average energy of the spectrum. The highest PVDR was
      found for a pink beam average energy of 124 keV. Conversely, the microbeam
      penumbra decreased with increasing energy before plateauing for energies above 90
      keV. The effect of bone on the PVDR was investigated at energies 60, 95 and 120
      keV. At depths greater than 20 mm beyond the bone/water interface there was
      almost no effect on the PVDR. In conclusion, the optimal energy range for MRT at
      IMBL is 90-120 keV, however when considering the IMBL flux at different energies,
      a spectrum with 95 keV weighted average energy was found to be the best
      compromise.

PMID- 29472080
TI  - Patient-specific organ and effective dose estimates in pediatric oncology
      computed tomography.
AB  - PURPOSE: Estimate organ and effective doses from computed tomography scans of
      pediatric oncologic patients using patient-specific information. MATERIALS AND
      METHODS: With IRB approval patient-specific scan parameters and patient size
      obtained from DICOM images and vendor-provided dose monitoring application were
      obtained for a cross-sectional study of 1250 pediatric patients from 0 through 20
      y-olds who underwent head, chest, abdomen-pelvis, or chest-abdomen-pelvis CT
      scans. Patients were categorized by age. Organ doses and effective doses were
      estimated using VirtualDoseTM CT based on patient-specific information, tube
      current modulation (TCM), and age-specific realistic phantoms. CTDIvol, DLP, and
      dose results were compared with those reported in the literature. RESULTS:
      CTDIvol and DLP varied widely as patient size varied. The 75th percentiles of
      CTDIvol and DLP were no greater than in the literature with the exception of head
      scans of 16-20 y-olds and of abdomen-pelvis scans of larger patients. Eye lens
      dose from a head scan was up to 69 mGy. Mean organ doses agreed with other
      studies at maximal difference of 38% for chest and 41% for abdomen-pelvis scans.
      Mean effective dose was generally higher for older patients. The highest
      effective doses were estimated for the 16-20 y-olds as: head 3.3 mSv, chest 4.1
      mSv, abdomen-pelvis 10.0 mSv, chest-abdomen-pelvis 14.0 mSv. CONCLUSION: Patient
      specific organ and effective doses have been estimated for pediatric oncologic
      patients from <1 through 20 y-olds. The effect of TCM was successfully accounted
      for in the estimates. Output parameters varied with patient size. CTDIvol and DLP
      results are useful for future protocol optimization.

PMID- 29472082
TI  - On the use of a novel Ferrous Xylenol-orange gelatin dosimeter for HDR
      brachytherapy commissioning and quality assurance testing.
AB  - PURPOSE: To evaluate a commercially available Ferrous-Xylenol Orange-Gel (FXG)
      dosimeter (TrueViewTM) coupled with Optical-Computed Tomography (OCT) read out,
      for 3D dose verification in an Ir-192 superficial brachytherapy application.
      METHODS: Two identical polyethylene containers filled with gel from the same
      batch were used. One was irradiated with an 18 MeV electron field to examine the
      dose-response linearity and obtain a calibration curve. A flap surface applicator
      was attached to the other to simulate treatment of a skin lesion. The dose
      distribution in the experimental set up was calculated with the TG-43 and the
      model based dose calculation (MBCA) algorithms of a commercial treatment planning
      system (TPS), as well as Monte Carlo (MC) simulation using the MCNP code.
      Measured and calculated dose distributions were spatially registered and
      compared. RESULTS: Apart from a region close to the container's neck, where gel
      measurements exhibited an over-response relative to MC calculations (probably due
      to stray light perturbation), an excellent agreement was observed between
      measurements and simulations. More than 97% of points within the 10% isodose line
      (80 cGy) met the gamma index criteria established from uncertainty analysis (5%/2
      mm). The corresponding passing rates for the comparison of experiment to
      calculations using the TG-43 and MBDCA options of the TPS were 57% and 92%,
      respectively. CONCLUSION: TrueViewTM is suitable for the quality assurance of
      demanding radiotherapy applications. Experimental results of this work confirm
      the advantage of the studied MBDCA over TG-43, expected from the improved account
      of scatter radiation in the treatment geometry.

PMID- 29472083
TI  - Quantifying the performance of two different types of commercial software
      programs for 3D patient dose reconstruction for prostate cancer patients: Machine
      log files vs. machine log files with EPID images.
AB  - We clarified the reconstructed 3D dose difference between two different
      commercial software programs (Mobius3D v2.0 and PerFRACTION v1.6.4). Five
      prostate cancer patients treated with IMRT (74 Gy/37 Fr) were studied. Log files
      and cine EPID images were acquired for each fraction. 3D patient dose was
      reconstructed using log files (Mobius3D) or log files with EPID imaging
      (PerFRACTION). The treatment planning dose was re-calculated on homogeneous and
      heterogeneous phantoms, and log files and cine EPID images were acquired.
      Measured doses were compared with the reconstructed point doses in the phantom.
      Next, we compared dosimetric metrics (mean dose for PTV, rectum, and bladder)
      calculated by Mobius3D and PerFRACTION for all fractions from five patients. Dose
      difference at isocenter between measurement and reconstructed dose for two
      software programs was within 3.0% in both homogeneous and heterogeneous phantoms.
      Moreover, the dose difference was larger using skip arc plan than that using full
      arc plan, especially for PerFRACTION (e.g., dose difference at isocenter for
      PerFRACTION: 0.34% for full arc plan vs. -4.50% for skip arc plan in patient 1).
      For patients, differences in dosimetric parameters were within 1% for almost all
      fractions. PerFRACTION had wider range of dose difference between first fraction
      and the other fractions than Mobius3D (e.g., maximum difference: 0.50% for
      Mobius3D vs. 1.85% for PerFRACTION), possibly because EPID may detect some types
      of MLC positioning errors such as miscalibration errors or mechanical backlash
      which cannot be detected by log files, or that EPID data might include image
      acquisition failure and image noise.

PMID- 29472084
TI  - Effect of image registration on 3D absorbed dose calculations in 177Lu-DOTATOC
      peptide receptor radionuclide therapy.
AB  - Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular
      radiotherapy) treatment, which consists of multiple administrations of a
      radiopharmaceutical labelled with 177Lu or 90Y. Through sequential functional
      imaging a patient specific 3D dosimetry can be derived. Multiple scans should be
      previously co-registered to allow accurate absorbed dose calculations. The
      purpose of this study is to evaluate the impact of image registration algorithms
      on 3D absorbed dose calculation. A cohort of patients was extracted from the
      database of a clinical trial in PRRT. They were administered with a single
      administration of 177Lu-DOTATOC. All patients underwent 5 SPECT/CT sequential
      scans at 1 h, 4 h, 24 h, 40 h, 70 h post-injection that were subsequently
      registered using rigid and deformable algorithms. A similarity index was
      calculated to compare rigid and deformable registration algorithms. 3D absorbed
      dose calculation was carried out with the Raydose Monte Carlo code. The
      similarity analysis demonstrated the superiority of the deformable registrations
      (p < .001). Average absorbed dose to the kidneys calculated using rigid image
      registration was consistently lower than the average absorbed dose calculated
      using the deformable algorithm (90% of cases), with percentage differences in the
      range [-19; +4]%. Absorbed dose to lesions were also consistently lower (90% of
      cases) when calculated with rigid image registration with absorbed dose
      differences in the range [-67.2; 100.7]%. Deformable image registration had a
      significant role in calculating 3D absorbed dose to organs or lesions with
      volumes smaller than 100 mL. Image based 3D dosimetry for 177Lu-DOTATOC PRRT is
      significantly affected by the type of algorithm used to register sequential
      SPECT/CT scans.

PMID- 29472085
TI  - Evaluation and comparison of second-check monitor unit calculation software with
      Pinnacle3 treatment planning system.
AB  - The purpose of this study was to evaluate and compare the accuracy of dose
      calculations in second check softwares (Diamond, IMSure, MuCheck, and RadCalc)
      against the Phillips Pinnacle3 treatment planning system. Eighteen previously
      treated patients' treatment planning files consisting of a total of 204 beams
      were exported from the Pinnacle3 TPS to each of the four second check software.
      Of these beams, 145 of the beams used were IMRT plans while 59 were VMAT arcs.
      The values were represented as a percent difference between primary and secondary
      calculations and used for statistical analysis. Box plots, Pearson Correlation,
      and Bland-Altman analysis were performed in MedCalc. The mean percent difference
      in calculated dose for Diamond, IMSure, MuCheck, and RadCalc from Pinnacle3 were 
      0.67%, 0.31%, 1.51% and -0.36%, respectively. The corresponding variances were
      calculated to be 0.07%, 0.13%, 0.08%, and 0.03%; and the largest percent
      differences were -7.9%, 9.70%, 9.39%, and 5.45%. The dose differences of each of
      the second check software in this study can vary considerably and VMAT plans have
      larger differences than IMRT. Among the four second check softwares, RadCalc
      values has shown a high agreement on average with low variation, and had the
      smallest percent range from Pinnacle3 values. The closest in average percent
      difference from the Pinnacle3data was the IMSure software, but suffered from
      significantly larger variance and percent range. The values reported by Diamond
      and MuCheck had significantly high percent differences with TPS values.

PMID- 29472086
TI  - Image quality of four-dimensional cone-beam computed tomography obtained at
      various gantry rotation speeds for liver stereotactic body radiation therapy with
      fiducial markers.
AB  - In this study, qualities of 4D cone-beam CT (CBCT) images obtained using various
      gantry rotation speeds (GRSs) for liver stereotactic body radiation therapy
      (SBRT) with fiducial markers were quantitatively evaluated. Abdominal phantom
      containing a fiducial marker was moved along a sinusoidal waveform, and 4D-CBCT
      images were acquired with GRSs of 50-200 degrees  min-1. We obtained the 4D-CBCT
      projection data from six patients who underwent liver SBRT and generated 4D-CBCT
      images at GRSs of 67-200 degrees  min-1, by varying the number of projection data
      points. The image quality was evaluated based on the signal-to-noise ratio (SNR),
      contrast-to-noise ratio (CNR), and structural similarity index (SSIM). The
      fiducial marker positions with different GRSs were compared with the setup values
      and a reference position in the phantom and clinical studies, respectively. The
      root mean square errors (RMSEs) were calculated relative to the reference
      positions. In the phantom study, the mean SNR, CNR, and SSIM decreased from 37.6
      to 10.1, from 39.8 to 10.1, and from 0.9 to 0.7, respectively, as the GRS
      increased from 50 to 200 degrees  min-1. The fiducial marker positions were
      within 2.0 mm at all GRSs. Similarly, in the clinical study, the mean SNR, CNR,
      and SSIM decreased from 50.4 to 13.7, from 24.2 to 6.0, and from 0.92 to 0.73,
      respectively. The mean RMSEs were 2.0, 2.1, and 3.6 mm for the GRSs of 67, 100,
      and 200 degrees  min-1, respectively. We conclude that GRSs of 67 and 85 degrees 
      min-1 yield images of acceptable quality for 4D-CBCT in liver SBRT with fiducial
      markers.

PMID- 29472087
TI  - An assessment of a 3D EPID-based dosimetry system using conventional two- and
      three-dimensional detectors for VMAT.
AB  - PURPOSE: To provide a 3D dosimetric evaluation of a commercial portal dosimetry
      system using 2D/3D detectors under ideal conditions using VMAT. METHODS: A 2D ion
      chamber array, radiochromic film and gel dosimeter were utilised to provide a
      dosimetric evaluation of transit phantom and pre-treatment 'fluence' EPID back
      projected dose distributions for a standard VMAT plan. In-house 2D and 3D gamma
      methods compared pass statistics relative to each dosimeter and TPS dose
      distributions. RESULTS: Fluence mode and transit EPID dose distributions back
      projected onto phantom geometry produced 2D gamma pass rates in excess of 97%
      relative to other tested detectors and exported TPS dose planes when a 3%, 3 mm
      global gamma criterion was applied. Use of a gel dosimeter within a glass vial
      allowed comparison of measured 3D dose distributions versus EPID 3D dose and TPS
      calculated distributions. 3D gamma comparisons between modalities at 3%, 3 mm
      gave pass rates in excess of 92%. Use of fluence mode was indicative of transit
      results under ideal conditions with slightly reduced dose definition.
      CONCLUSIONS: 3D EPID back projected dose distributions were validated against
      detectors in both 2D and 3D. Cross validation of transit dose delivered to a
      patient is limited due to reasons of practicality and the tests presented are
      recommended as a guideline for 3D EPID dosimetry commissioning; allowing direct
      comparison between detector, TPS, fluence and transit modes. The results indicate
      achievable gamma scores for a complex VMAT plan in a homogenous phantom geometry
      and contributes to growing experience of 3D EPID dosimetry.

PMID- 29472088
TI  - Occupational exposures during abdominal fluoroscopically guided interventional
      procedures for different patient sizes - A Monte Carlo approach.
AB  - In this study we evaluated the occupational exposures during an abdominal
      fluoroscopically guided interventional radiology procedure. We investigated the
      relation between the Body Mass Index (BMI), of the patient, and the conversion
      coefficient values (CC) for a set of dosimetric quantities, used to assess the
      exposure risks of medical radiation workers. The study was performed using a set
      of male and female virtual anthropomorphic phantoms, of different body weights
      and sizes. In addition to these phantoms, a female and a male phantom, named
      FASH3 and MASH3 (reference virtual anthropomorphic phantoms), were also used to
      represent the medical radiation workers. The CC values, obtained as a function of
      the dose area product, were calculated for 87 exposure scenarios. In each
      exposure scenario, three phantoms, implemented in the MCNPX 2.7.0 code, were
      simultaneously used. These phantoms were utilized to represent a patient and
      medical radiation workers. The results showed that increasing the BMI of the
      patient, adjusted for each patient protocol, the CC values for medical radiation
      workers decrease. It is important to note that these results were obtained with
      fixed exposure parameters.

PMID- 29472089
TI  - Investigation of the XCAT phantom as a validation tool in cardiac MRI tracking
      algorithms.
AB  - PURPOSE: To describe our magnetic resonance imaging (MRI) simulated
      implementation of the 4D digital extended cardio torso (XCAT) phantom to validate
      our previously developed cardiac tracking techniques. Real-time tracking will
      play an important role in the non-invasive treatment of atrial fibrillation with
      MRI-guided radiosurgery. In addition, to show how quantifiable measures of
      tracking accuracy and patient-specific physiology could influence MRI tracking
      algorithm design. METHODS: Twenty virtual patients were subjected to simulated
      MRI scans that closely model the proposed real-world scenario to allow
      verification of the tracking technique's algorithm. The generated phantoms
      provide ground-truth motions which were compared to the target motions output
      from our tracking algorithm. The patient-specific tracking error, ep, was the 3D
      difference (vector length) between the ground-truth and algorithm trajectories.
      The tracking errors of two combinations of new tracking algorithm functions that
      were anticipated to improve tracking accuracy were studied. Additionally, the
      correlation of key physiological parameters with tracking accuracy was
      investigated. RESULTS: Our original cardiac tracking algorithm resulted in a mean
      tracking error of 3.7 +/- 0.6 mm over all virtual patients. The two combinations
      of tracking functions demonstrated comparable mean tracking errors however
      indicating that the optimal tracking algorithm may be patient-specific.
      CONCLUSIONS: Current and future MRI tracking strategies are likely to benefit
      from this virtual validation method since no time-resolved 4D ground-truth signal
      can currently be derived from purely image-based studies.

PMID- 29472090
TI  - Non-invasive characterization of coronary artery atherosclerotic plaque using
      dual energy CT: Explanation in ex-vivo samples.
AB  - PURPOSE: In this study non-calcified plaque composition is evaluated by Dual
      Energy CT (DECT). Energy Dispersive X-ray Spectroscopy (EDS) has been used to
      study the Plaque composition. An attempt has been made to explain the DECT
      results with EDS analysis. METHODS: Thirty-two ex-vivo human cadaver coronary
      artery samples were scanned by DECT and data was evaluated to calculate their
      effective atomic number and electron density (Zeff & rhoe) by inversion method.
      Result of DECT was compared with pathology to assess their differentiating
      capability. The EDS study was used to explain DECT outcome. RESULTS: DECT study
      was able to differentiate vulnerable plaque from stable with 87% accuracy (area
      under the curve (AUC):0.85 [95% confidence interval {CI}:0.73-0.98}] and Kappa
      Coefficient (KC):0.75 with respect to pathology. EDS revealed significant
      compositional difference in vulnerable and stable plaque at p < .05. The weight
      percentage of higher atomic number elements like F, Na, Mg, S, Si, P, Cl, K and
      Ca was found to be slightly more in vulnerable plaques as compared to a stable
      plaque. EDS also revealed a significantly increased weight percentage of nitrogen
      in stable plaques. CONCLUSIONS: The EDS results were able to explain the outcomes
      of DECT study. This study conclusively explains the physics of DECT as a tool to
      assess the nature of non-calcified plaques as vulnerable and stable. The method
      proposed in this study allows for differentiation between vulnerable and stable
      plaque using DECT.

PMID- 29472091
TI  - Assessment of the variation in CT scanner performance (image quality and
      Hounsfield units) with scan parameters, for image optimisation in radiotherapy
      treatment planning.
AB  - PURPOSE: To define a method and investigate how the adjustment of scan parameters
      affected the image quality and Hounsfield units (HUs) on a CT scanner used for
      radiotherapy treatment planning. A lack of similar investigations in the
      literature may be a contributing factor in the apparent reluctance to optimise
      radiotherapy CT protocols. METHOD: A Catphan phantom was used to assess how image
      quality on a Toshiba Aquilion LB scanner changed with scan parameters.
      Acquisition and reconstruction field-of-view (FOV), collimation, image slice
      thickness, effective mAs per rotation and reconstruction algorithm were varied.
      Changes were assessed for HUs of different materials, high contrast spatial
      resolution (HCSR), contrast-noise ratio (CNR), HU uniformity, scan direction low
      contrast and CT dose-index. RESULTS: CNR and HCSR varied most with reconstruction
      algorithm, reconstruction FOV and effective mAs. Collimation, but not image slice
      width, had a significant effect on CT dose-index with narrower collimation giving
      higher doses. Dose increased with effective mAs. Highest HU differences were seen
      when changing reconstruction algorithm: 56 HU for densities close to water and
      117 HU for bone-like materials. Acquisition FOV affected the HUs but
      reconstruction FOV and effective mAs did not. CONCLUSIONS: All the scan
      parameters investigated affected the image quality metrics. Reconstruction
      algorithm, reconstruction FOV, collimation and effective mAs were most important.
      Reconstruction algorithm and acquisition FOV had significant effect on HU. The
      methodology is applicable to radiotherapy CT scanners when investigating image
      quality optimisation, prior to assessing the impact of scan protocol changes on
      clinical CT images and treatment plans.

PMID- 29472092
TI  - IEC 61331-1: A new setup for testing lead free X-ray protective clothing.
AB  - PURPOSE: Lead free protective clothing can create a higher part of secondary
      radiation (SR) than products that are based on lead. Hence, the attenuation
      properties may be downgraded. The international measuring standard IEC 61331
      1:2014 declares the "inverse broad beam geometry" (IBG) as standard method, which
      has recently been modified to IBG* by the Physikalisch Technische Bundesanstalt
      (PTB). Because of the unspecific partial irradiation of the ionization chamber
      problems in the evaluation of lead equivalence values (LEVs) can occur. An
      alternative method proposed in this paper overcomes these problems. MATERIALS AND
      METHODS: The alternative setup "modified broad beam geometry" (BBG*) was tested
      and compared to the IBG* method by performing Monte Carlo simulations and
      radiation measurements including several lead-composite and lead-free protective
      materials. RESULTS: Simulations show a reduced collection efficiency of SR under
      IBG* whereas BBG* features a high degree of SR collection. Material samples with
      a high amount of SR can feature up to 8% higher LEVs compared to IBG*. For most
      of the currently salable materials the differences of BBG* vs IBG* amount to <3%
      (0.25 mm LEV) and <1% (0.50 mm LEV). In special cases the currently practiced
      method can lead to heavier protective clothings. CONCLUSIONS: The proposed BBG*
      setup meets the specifications of the IEC standard with respect to energy
      response and SR collection. The method should be implemented in the IEC standard.

PMID- 29472093
TI  - Image quality for radiotherapy CT simulators with different scanner bore size.
AB  - PURPOSE: We compare image quality parameters derived from phantom images taken on
      three commercially available radiotherapy CT simulators. To make an unbiased
      evaluation, we assured images were obtained with the same surface dose measured
      using XR-QA2 model GafChromicTM film placed at the imaging phantom surface for
      all three CT-simulators. METHODS: Radiotherapy CT simulators GE LS 16, Philips
      Brilliance Big Bore, and Toshiba Aquilion LB were compared in terms of spatial
      resolution, low contrast detectability, image uniformity, and contrast to noise
      ratio using CATPHAN-504 phantom, scanned with Head and Pelvis protocols. Dose was
      measured at phantom surface, with CT scans repeated until doses on all scanners
      were within 2%. RESULTS: In terms of spatial resolution, the GE simulator appears
      slightly better, while Philips CT images are superior in terms of SNR for both
      scanning protocols. The CNR results show that Philips CT images appear to be
      better, except for high Z material, while Toshiba appears to fit in between the
      two simulators. CONCLUSIONS: While the image quality parameters for three RT CT
      simulators show comparable results, the scanner bore size is of vital importance
      in various radiotherapy applications. Since the image quality is a function of a
      large number of confounding parameters, any loss in image quality due to scanner
      bore size could be compensated by the appropriate choice of scanning parameters,
      including the exposure and by balancing between the additional imaging dose to
      the patient and high image quality required in highly conformal RT techniques.

PMID- 29472094
TI  - Multi-institutional comparison of computer-based independent dose calculation for
      intensity modulated radiation therapy and volumetric modulated arc therapy.
AB  - PURPOSE: No multi-institutional studies of computer-based independent dose
      calculation have addressed the discrepancies among radiotherapy treatment
      planning systems (TPSs) and the verification programs for intensity modulated
      radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). We
      conducted a multi-institutional study to investigate whether +/-5% is a
      reasonable action level for independent dose calculation for IMRT/VMAT. METHODS:
      In total, 477 IMRT/VMAT plans for prostate or head and neck (H&N) malignancies
      were retrospectively analyzed using a modified Clarkson-based commercial
      verification program. The doses from the TPSs and verification programs were
      compared using the mean +/-1 standard deviation (SD). RESULTS: In the TPS
      calculated dose comparisons for prostate and H&N malignancies, the sliding window
      (SW) technique (-2.5 +/- 1.8% and -5.3 +/- 2.6%) showed greater negative
      systematic differences than the step-and-shoot (S&S) technique (-0.3 +/- 2.2% and
      -0.8 +/- 2.2%). The VMAT dose differences for prostate and H&N malignancies were
      0.9 +/- 1.8% and 1.1 +/- 3.3%, respectively. The SDs were larger for the H&N
      plans than for the prostate plans in both IMRT and VMAT. Such plans including
      more out-of-field control points showed greater systematic differences and SDs.
      CONCLUSIONS: This study will help individual institutions to establish an action
      level for agreement between primary calculations and verification for IMRT/VMAT.
      A local dose difference of +/-5% at a point within the planning target volume
      (above -350 HU) may be a reasonable action level.

PMID- 29472095
TI  - Dosimetric evaluation of modern radiation therapy techniques for left breast in
      deep-inspiration breath-hold.
AB  - PURPOSE: The dosimetric differences between four radiation therapy techniques for
      left sided whole breast irradiation were evaluated side by side in the same
      patient population. METHODS: Radiotherapy treatment plans were retrospectively
      created with Accuray TomoDirect (TD), Elekta Volumetric Modulated Arc Therapy (E
      VMAT), Varian RapidArc (RA) and Field-in-field (FinF) technique for 20 patients,
      who had received left breast irradiation during deep-inspiration breath-hold.
      Dose characteristics of planning target volume and organs at risk were compared.
      RESULTS: The E-VMAT, TD and RA treatment plans had higher target coverage (V95%)
      than FinF plans (97.7-98.3% vs. 96.6%). The low-dose spillage to contralateral
      breast and lung was smaller with FinF and TD (mean 0.1 and 0.3 Gy) compared to E
      VMAT and RA (mean 0.6 and 0.9 Gy). E-VMAT, RA and TD techniques were more
      effective than FinF in sparing left anterior descending artery (mean 4.0, 4.2 and
      4.7 Gy vs. 6.1 Gy, respectively). CONCLUSIONS: In whole breast irradiation TD, E
      VMAT and RA plans generated in this study achieved higher dose coverage and
      sparing of organs from the high dose in the vicinity of the PTV. The advantage of
      calculated FinF plans is the lowest dose on contralateral organs. The choice of
      the technique used should be weighted by each institution taking into account the
      dose characteristics of each technique and its fit with patient anatomy bearing
      in mind the increased workload of using modulated techniques and the increased
      beam on time.

PMID- 29472096
TI  - Prediction of GTV median dose differences eases Monte Carlo re-prescription in
      lung SBRT.
AB  - BACKGROUND AND PURPOSE: The use of Monte Carlo (MC) dose calculation algorithm
      for lung patients treated with stereotactic body radiotherapy (SBRT) can be
      challenging. Prescription in low density media and time-consuming optimization
      conducted CyberKnife centers to propose an equivalent path length (EPL)-to-MC re
      prescription method based on GTV median dose. Unknown at the time of planning,
      GTV D50% practical application remains difficult. The current study aims at
      creating a re-prescription predictive model in order to limit conflicting dose
      value during EPL optimization. MATERIAL AND METHODS: 129 patients planned with
      EPL algorithm were recalculated with MC. Relative GTV_D50% discrepancies were
      assessed and influencing parameters identified using wrapper feature selection.
      Based on best descriptive parameters, predictive nomogram was built from
      multivariate linear regression. EPL-to-MC OARs near max-dose discrepancies were
      reported. RESULTS: The differences in GTV_D50% (median 10%, SD: 9%) between MC
      and EPL were significantly (p < .001) impacted by the lesion's surface-to-volume
      ratio and the average relative electronic density of the GTV and the GTV's 15 mm
      shell. Built upon those parameters, a nomogram (R2 = 0.79, SE = 4%) predicting
      the GTV_D50% discrepancies was created. Furthermore EPL-to-MC OAR dose tolerance
      limit showed a strong linear correlation with coefficient range [0.84-0.99].
      CONCLUSION: Good prediction on the required re-prescription can be achieved prior
      planning using our nomogram. Based on strong linear correlation between EPL and
      MC for OARs near max-dose, further restriction on dose constraints during the EPL
      optimization can be warranted. This a priori knowledge eases the re-prescription
      process in limiting conflicting dose value.

PMID- 29472098
TI  - Comparison of relative renal functions calculated with 99mTc-DTPA and 99mTc-DMSA
      for kidney patients of wide age ranges.
AB  - Renal scintigraphy is an imaging method that uses small amount of radioactive
      materials called radiotracers, a Gamma camera and a computer to evaluate kidney
      functions and its anatomy. The present work reports the comparison of the
      relative renal functions (RRF) calculated with technetium-99m dimercaptosuccinic
      acid (99mTc-DMSA) and technetium-99m diethylenetriaminepentaacetic acid (99mTc
      DTPA) for kidney patients of ages between 5 months and 71 years. A total of 50
      patients including 29 male and 21 female has been selected and studied for
      renography. The mean RRFs have been found to be 52.68 +/- 23.63% and 47.32 +/-
      23.63% respectively for the left and right kidneys with 99mTc-DMSA measurement.
      With 99mTc-DTPA the values are 52.74 +/- 23.54% and 47.26 +/- 23.54% for the
      same. In bivariate correlation analysis, a significant positive correlation (r =
      0.996, P < .001) has been found between the RRFs calculated with the two methods.
      Following the patients' diagnosis, in ANOVA test, no difference has been found
      between the RRFs calculated for the left and right kidneys. In Bland-Altman
      plots, the mean difference between the two methods has been found to be 0.1 and
      the correlation limit lies between -4.3 and 4.2. According to the result obtained
      in the present work, both the 99mTc-DMSA and 99mTc-DTPA scanning methods provide
      almost the same RRF values. It is, therefore, always not necessary to calculate
      the RRFs with both the methods. This study suggests that 99mTc-DMSA may be the
      primary choice for the evaluation of RRF, but if the glomerular filtration rate
      (GFR) and renogram curve are required, 99mTc-DTPA can be the obvious selection.

PMID- 29472097
TI  - The influence of the image registration method on the adaptive radiotherapy. A
      proof of the principle in a selected case of prostate IMRT.
AB  - PURPOSE: To analyse the influence of the image registration method on the
      adaptive radiotherapy of an IMRT prostate treatment, and to compare the dose
      accumulation according to 3 different image registration methods with the planned
      dose. MATERIAL AND METHODS: The IMRT prostate patient was CT imaged 3 times
      throughout his treatment. The prostate, PTV, rectum and bladder were segmented on
      each CT. A Rigid, a deformable (DIR) B-spline and a DIR with landmarks
      registration algorithms were employed. The difference between the accumulated
      doses and planned doses were evaluated by the gamma index. The Dice coefficient
      and Hausdorff distance was used to evaluate the overlap between volumes, to
      quantify the quality of the registration. RESULTS: When comparing adaptive vs no
      adaptive RT, the gamma index calculation showed large differences depending on
      the image registration method (as much as 87.6% in the case of DIR B-spline). The
      quality of the registration was evaluated using an index such as the Dice
      coefficient. This showed that the best result was obtained with DIR with
      landmarks compared with the rest and it was always above 0.77, reported as a
      recommended minimum value for prostate studies in a multi-centre review.
      CONCLUSIONS: Apart from showing the importance of the application of an adaptive
      RT protocol in a particular treatment, this work shows that the election of the
      registration method is decisive in the result of the adaptive radiotherapy and
      dose accumulation.

PMID- 29472099
TI  - Neurotransmitter activity is linked to outcome following subthalamic deep brain
      stimulation in Parkinson's disease.
AB  - INTRODUCTION: While the mechanisms underlying the therapeutic effects of deep
      brain stimulation (DBS) in Parkinson's Disease (PD) are not yet fully understood,
      DBS appears to exert a wide range of neurochemical effects on the network level,
      thought to arise from activation of inhibitory and excitatory pathways. The
      activity within the primary inhibitory (GABAergic) and excitatory (glutamatergic)
      neurotransmitter systems may therefore play an important role in the therapeutic
      efficacy of DBS in PD. The purpose of this study was to investigate abnormalities
      in GABA-ergic and glutamatergic neurotransmission in PD, and to examine the link
      between neurotransmitter levels and outcome following DBS. METHODS: Magnetic
      resonance spectra were acquired from the pons and basal ganglia in sixteen
      patients with PD and sixteen matched control participants. GABA and glutamate
      levels were quantified with LCModel, an automated spectral fitting package.
      Fourteen patients subsequently underwent DBS, and PD symptoms were evaluated with
      the MDS-UPDRS at baseline and six months after surgery. The efficacy of DBS
      treatment was evaluated from the percentage improvement in MDS-UPDRS scores.
      RESULTS: Basal ganglia GABA levels were significantly higher in PD patients
      relative to control participants (p < 0.01), while pontine glutamate + glutamine
      (Glx) levels were significantly lower in patients with PD (p < 0.05). While GABA
      levels were not significantly related to outcome post-surgery, basal ganglia
      glutamate levels emerged as a significant predictor of outcome, suggesting a
      possible role for glutamatergic neurotransmission in the therapeutic mechanism of
      DBS. CONCLUSION: GABAergic and glutamatergic neurotransmission is altered in PD,
      and glutamatergic activity in particular may influence outcome post-surgery.

PMID- 29472100
TI  - Diablo: A Double-Edged Sword in Cancer?

PMID- 29472101
TI  - Corrigendum to "Revitalisation of metal-contaminated, EDTA-washed soil by
      addition of unpolluted soil, compost and biochar: Effects on soil enzyme
      activity, microbial community composition and abundance" [Chemosphere 193 (2018)
      729-734].

PMID- 29472102
TI  - Modeling human pancreatic beta cell dedifferentiation.
AB  - OBJECTIVE: Dedifferentiation could explain reduced functional pancreatic beta
      cell mass in type 2 diabetes (T2D). METHODS: Here we model human beta-cell
      dedifferentiation using growth factor stimulation in the human beta-cell line,
      EndoC-betaH1, and human pancreatic islets. RESULTS: Fibroblast growth factor 2
      (FGF2) treatment reduced expression of beta-cell markers, (INS, MAFB, SLC2A2,
      SLC30A8, and GCK) and activated ectopic expression of MYC, HES1, SOX9, and
      NEUROG3. FGF2-induced dedifferentiation was time- and dose-dependent and
      reversible upon wash-out. Furthermore, FGF2 treatment induced expression of
      TNFRSF11B, a decoy receptor for RANKL and protected beta-cells against RANKL
      signaling. Finally, analyses of transcriptomic data revealed increased FGF2
      expression in ductal, endothelial, and stellate cells in pancreas from T2D
      patients, whereas FGFR1, SOX,9 and HES1 expression increased in islets from T2D
      patients. CONCLUSIONS: We thus developed an FGF2-induced model of human beta-cell
      dedifferentiation, identified new markers of dedifferentiation, and found
      evidence for increased pancreatic FGF2, FGFR1, and beta-cell dedifferentiation in
      T2D.

PMID- 29472104
TI  - Lighting Up Alpha-synuclein Oligomers.

PMID- 29472105
TI  - Identification of patients at high risk for post-discharge venous thromboembolism
      after hepato-pancreato-biliary surgery: which patients benefit from extended
      thromboprophylaxis?
AB  - BACKGROUND: The objective of the current study was to define risk factors
      associated with the 30-day post-operative risk of VTE after HPB surgery and
      create a model to identify patients at highest risk of post-discharge VTE.
      METHODS: Patients who underwent hepatectomy or pancreatectomy in the ACS-NSQIP
      Participant Use Files 2011-2015 were identified. Logistic regression modeling was
      used; a model to predict post-discharge VTE was developed. Model discrimination
      was tested using area under the curve (AUC). RESULTS: Among 48,860 patients, the
      overall 30-day incidence of VTE after hepatectomy and pancreatectomy was 3.2% (n
      = 1580) with 1.1% (n = 543) of VTE events occurring after discharge. Patients who
      developed post-discharge VTE were more likely to be white, had a higher median
      BMI, have undergone pancreatic surgery, had longer median operative times, and to
      have had a transfusion. A weighted prediction model demonstrated good calibration
      and fair discrimination (AUC = 0.63). A score of >=-4.50 had maximum sensitivity
      and specificity, resulting in 44% of patients being treating with prophylaxis for
      an overall VTE risk of 1.1%. CONCLUSIONS: Utilizing independent factors
      associated with post-discharge VTE, a prediction model was able to stratify
      patients according to risk of VTE and may help identify patients who are most
      likely to benefit from pharmacoprophylaxis.

PMID- 29472103
TI  - p204 Is Required for Canonical Lipopolysaccharide-induced TLR4 Signaling in Mice.
AB  - p204, a murine member of an interferon-inducible p200 family, was reported to
      recognize intracellular viral and bacterial DNAs, however, its role in the innate
      immunity in vivo remains unknown due to the lack of p204-deficient animal models.
      In this study we first generated the p204-/- mice. Unexpectedly, p204 deficiency
      led to significant defect in extracellular LPS signaling in macrophages, as
      demonstrated by dramatic reductions of LPS-mediated IFN-beta and pro-inflammatory
      cytokines. The serum levels of IFN-beta and pro-inflammatory cytokines were also
      significantly reduced in p204-/- mice following LPS challenge. In addition, p204
      /- mice were resistant to LPS-induced shock. LPS-activated NF-KB and IRF-3
      pathways were all defective in p204-deficient macrophages. p204 binds to TLR4
      through its Pyrin domain, and it is required for the dimerization of TLR4
      following LPS-challenge. Collectively, p204 is a critical component of canonical
      LPS-TLR4 signaling pathway, and these studies also suggest that p204 could be a
      potential target to prevent and treat inflammatory and infectious diseases.

PMID- 29472106
TI  - Open versus laparoscopic portal lymphadenectomy in gallbladder cancer: is there a
      difference in lymph node yield?
AB  - BACKGROUND: Gallbladder cancer (GBC) is the most common biliary tract malignancy.
      Because it commonly metastasizes via lymphatics, portal lymphadenectomy should be
      included in oncologic resections. This study aimed to compare the oncologic
      equivalence of the laparoscopic versus open technique by evaluating lymph node
      (LN) yield. METHODS: The 2010-2012 National Cancer Data Base identified patients
      who underwent laparoscopic or open resection of GBC with dedicated
      lymphadenectomy. LN yield was compared by resection method. Variables associated
      with LN yield >=3 were identified. RESULTS: Of 1524 patients identified, 52% were
      intended to undergo laparoscopic surgery, with 20% of these patients converted to
      open. Collection of >=3 LNs following open resection (47%) was higher than for
      laparoscopic resection (34%), p < 0.001. Operations performed at high-volume
      (aOR:1.74, p < 0.001) and/or academic centers (aOR:1.70, p = 0.024) had superior
      LN yield. LN yield was not associated with overall survival (aHR:0.93, p =
      0.493). CONCLUSIONS: In this analysis of national data, LN yield following
      laparoscopic resection for GBC was significantly lower than following open
      resection. Open resection is more frequently performed at academic centers,
      possibly to assure adequate oncologic resection. Enforcing consensus guidelines
      for lymphadenectomy in gallbladder cancer will optimize outcomes as minimally
      invasive approaches evolve.

PMID- 29472107
TI  - Are antimicrobial stewardship programs effective strategies for preventing
      antibiotic resistance? A systematic review.
AB  - BACKGROUND: Antimicrobial stewardship programs (ASPs) have been proposed as a
      solution for the global burden of antibiotic resistance, despite the lack of
      evidence on the subject. OBJECTIVE: To analyze the role of ASPs in reducing
      bacterial resistance to antibiotics in hospital settings. DATA SOURCES: A review
      in PubMed, Scopus, LILACS, and SciELO databases was performed. The period
      analyzed was January 1, 2012-January 4, 2017. ELIGIBILITY CRITERIA: Studies that
      related ASPs to bacterial resistance. DATA EXTRACTION: All studies that did not
      focus on ASPs were removed. Antifungal and antiviral programs were excluded.
      RESULTS: Only 8 studies had quasi-experimental designs, and none were controlled
      trials. ASP strategies and microorganism-antibiotic pairs evaluated varied
      widely. Seven studies were classified as presenting clearly positive results, 3
      had limited positive results, 7 had doubtful results, 4 had negative results, and
      5 had noninterpretable results. The implementation of new infection control
      practices occurred in 7 studies. LIMITATIONS: There are yet few studies on this
      matter, and most of them have inadequate study designs. Great heterogeneity
      between study features was detrimental to drawing evidence-based conclusions.
      CONCLUSIONS: There is no solid evidence that ASPs are effective in reducing
      antibiotic resistance in hospital settings. We uphold the need for more studies
      with appropriate study designs, standardized ASP interventions targeting common
      microorganism-antibiotic pairs, and avoiding simultaneous implementation of
      infection control practices.

PMID- 29472108
TI  - Pediatric issues in thrombosis and hemostasis: The how and why of venous
      thromboembolism risk stratification in hospitalized children.
AB  - Multiple observational studies have identified risk factors for venous
      thromboembolism (VTE) in hospitalized children, but very few interventional
      studies have assessed the safety and efficacy of thromboprophylaxis in this
      population. In recent years, however, evidence in pediatric VTE risk
      stratification has grown considerably. This has led to the conception of a
      pediatric subpopulation-specific risk-based paradigm for mechanical and
      pharmacological thromboprophylaxis in hospitalized children. More research is
      required to validate and further refine pediatric subpopulation-specific risk
      models and to subsequently investigate risk-stratified thromboprophylaxis
      strategies for hospitalized children.

PMID- 29472109
TI  - Bradycardia: What is the mechanism?

PMID- 29472110
TI  - Experimental confirmation of a character-facing bias in literacy development.
AB  - When learning to write, children often mirror-reverse individual letters. For
      children learning to use the Latin alphabet, in a left-to-right writing culture,
      letters that appear to face left (such as J and Z) seem to be more prone to
      reversal than those that appear to face right (such as B and C). It has been
      proposed that, because most asymmetrical Latin letters face right, children
      statistically learn this general regularity and are subsequently biased to write
      any letter rightward. The evidence for this character-facing bias is
      circumstantial, however, because letter-facing direction is confounded with other
      factors that could affect error rates; for instance, J and Z are left-facing, but
      they are also infrequent. We report the first controlled experimental test of the
      character-facing bias. We taught 43 Scottish primary schoolchildren (aged 4.8-5.8
      years) four artificial, letter-like characters, two of which were left-facing and
      two of which were right-facing. The characters were novel and so were not subject
      to prior exposure effects, and alternate groups of children were assigned to
      identical but mirror-reflected character sets. Children were three times more
      likely to mirror-write a novel character they had learned in a left-facing format
      than to mirror-write one they had learned in a right-facing format. This provides
      the first experimental confirmation of the character-facing bias in literacy
      development and suggests that implicit knowledge acquired from exposure to
      written language is readily generalized to novel letter-like forms.

PMID- 29472111
TI  - Lady Windermere syndrome in Castile and Leon.
AB  - INTRODUCTION: Lady Windermere syndrome (LWS) is a pulmonary disease caused by
      Mycobacterium avium complex (MAC). The objective of this study is to ascertain
      its frequency and characteristics in the northern area of the autonomous
      community of Castile and Leon. METHODS: A retrospective study of patients with
      MAC isolates in respiratory samples from five public hospitals in the autonomous
      community over a six-year period, following the ATS/IDSA criteria. The MAC
      strains were identified by GenoType Mycobacterium reverse hybridisation probes or
      PCR-RFLP analysis of the hsp65 gene. RESULTS: Of 183 cases of MAC identified,
      only five women (2.7%) aged 68.8+/-10.7years met LWS criteria. In three cases,
      MAC was isolated jointly and intermittently with other pathogens. Only one
      patient was treated according to ATS/IDSA criteria. DISCUSSION: LWS remains
      underestimated, with affected patients representing a significant burden on
      healthcare resources over long periods of time. As a result, greater
      microbiological and therapeutic knowledge of the syndrome is needed.

PMID- 29472112
TI  - Abnormal Heavy/Light Chain Ratio and Matched Pair Suppression Increase Residual
      Disease Detection Sensitivity in Patients With Multiple Myeloma With Deep
      Responses.
AB  - BACKGROUND: Heavy/light chain (HLC) assay can quantify involved as well as
      uninvolved immunoglobulin pairs and is used to detect monoclonal proteins.
      PATIENTS AND METHODS: We compared the sensitivity between HLC assay and serum
      protein electrophoresis, serum immunofixation electrophoresis (IFE), and free
      light chain (FLC) assay in patients with symptomatic multiple myeloma (n = 111)
      whose responses were stable disease or better. RESULTS: Among patients with
      negative IFE and normal FLC ratios, 84.4% (38 of 45) and 80% (36 of 45) exhibited
      normal HLC ratios and no pair suppression, respectively (13.3% [6 of 45],
      moderate pair suppression and 6.7% [3 of 45], severe pair suppression). The lower
      the monoclonal protein levels, the more the possibility that the patients had
      normal HLC ratios and no matched pair suppression (both P < .000001). HLC ratios
      or pair suppression combined with IFE results and FLC ratios were more sensitive
      for detecting monoclonal proteins than were IFE results and FLC ratios alone (P =
      .016 and .0039, respectively). A combination of all 4 methods (IFE, FLC, HLC, and
      pair suppression) was far more sensitive than were IFE findings plus FLC ratios
      alone (P = .00024). CONCLUSION: Abnormal HLC ratios and HLC-matched pair
      suppression can increase the sensitivity for detecting residual disease in
      patients with multiple myeloma with deep responses.

PMID- 29472113
TI  - Revised Value of Contrast-Enhanced Ultrasound for Solid Hypo-Echoic Thyroid
      Nodules Graded with the Thyroid Imaging Reporting and Data System.
AB  - The use of ultrasound in differentiation of benign and malignant solid hypo
      echoic thyroid nodules is a dilemma in clinical practice. The aim of this study
      was to investigate the revised value of contrast-enhanced ultrasound (CEUS) for
      differentiating solid hypo-echoic thyroid nodules using the Thyroid Imaging
      Reporting and Data System (TI-RADS).The study included 135 patients with 135
      nodules confirmed by fine-needle aspiration and/or surgery. Every nodule
      underwent both conventional US and CEUS. Binary logistic regression analysis for
      conventional US features revealed that irregular shape, microcalcification and
      height greater than width were significant malignant predictive features. Binary
      logistic analysis for CEUS features indicated that hetero-enhancement, slow wash
      in, an ill-defined enhancement border and fast wash-out were significantly
      associated with malignancy. The areas under the curve of the TI-RADS, CEUS and
      the combination were 0.806, 0.934 and 0.950, respectively. CEUS is a potentially
      useful tool in the differentiation of solid hypo-echoic thyroid nodules.

PMID- 29472114
TI  - Enlarged Size and Impaired Elastic Properties of the Ascending Aorta are
      Associated with Endothelial Dysfunction and Elevated Plasma Matrix
      Metalloproteinase-2 Level in Patients with Bicuspid Aortic Valve.
AB  - The aim of this study was to test whether enlarged size and impaired elastic
      properties of the ascending aorta are associated with impaired endothelial
      function and increases in plasma matrix metalloproteinase (MMP)-2 concentrations
      in patients with bicuspid aortic valve (BAV) without significant valvular
      dysfunction. The size and the elasticity of the ascending aorta and the flow
      mediated vasodilation (FMD) in the brachial artery in response to hyperemia were
      evaluated with 2-D echocardiography and high-frequency linear ultrasound in 42
      patients with BAV without significant valvular dysfunction and 30 age- and sex
      matched healthy controls. In the BAV group, diastolic ascending aortic diameter
      (AoD) (32.1 +/- 8.1 mm vs. 25.3 +/- 3.6 mm, p <0.001) and aortic stiffness index
      (8.0 +/- 5.3 vs. 4.0 +/- 1.8, p <0.001) were significantly higher, and aortic
      strain (7.4 +/- 3.6% vs. 11.1 +/- 3.0%, p <0.001) and aortic distensibility (7.4
      +/- 4.1 * 10-6cm2/dyn vs. 11.1 +/- 4.3 * 10-6cm2/dyn, p <0.001) were
      significantly lower than those in the control group. The BAV group also had lower
      FMD (6.5 +/- 2.2% vs. 11.9 +/- 2.7%, p <0.001) and higher plasma MMP-2 levels
      (226.7 +/- 55.0 ng/mL vs. 177.0 +/- 45.3 ng/mL, p <0.001) compared with the
      control group. In the BAV group, AoD, aortic strain, aortic stiffness index and
      aortic distensibility significantly correlated with FMD and MMP-2 (all p <0.05).
      The multivariable linear regression analysis further indicated that FMD and MMP-2
      were independently associated with AoD (beta = -1.1, p = 0.005, and beta = 0.09,
      p <0.001, respectively). These findings suggest that enlarged size and impaired
      elastic properties of the ascending aorta are associated with endothelial
      dysfunction and elevated plasma MMP-2 level in patients with BAV without
      significant valvular dysfunction. FMD and plasma MMP-2 level are the significant
      and independent predictors of dilation of the ascending aorta in patients with
      BAV.

PMID- 29472115
TI  - CT colonography provides new insights into interval cancers.

PMID- 29472116
TI  - Post-imaging colorectal cancer or interval cancer rates after CT colonography: a
      systematic review and meta-analysis.
AB  - BACKGROUND: CT colonography is highly sensitive for colorectal cancer, but
      interval or post-imaging colorectal cancer rates (diagnosis of cancer after
      initial negative CT colonography) are unknown, as are their underlying causes. We
      did a systematic review and meta-analysis of post-CT colonography and post
      imaging colorectal cancer rates and causes to address this gap in understanding.
      METHODS: We systematically searched MEDLINE, Embase, and the Cochrane Central
      Register of Controlled Trials. We included randomised, cohort, cross-sectional,
      or case-control studies published between Jan 1, 1994, and Feb 28, 2017, using CT
      colonography done according to international consensus standards with the aim of
      detecting cancer or polyps, and reporting post-imaging colorectal cancer rates or
      sufficient data to allow their calculation. We excluded studies in which all CT
      colonographies were done because of incomplete colonoscopy or if CT colonography
      was done with knowledge of colonoscopy findings. We contacted authors of
      component studies for additional data where necessary for retrospective CT
      colonography image review and causes for each post-imaging colorectal cancer. Two
      independent reviewers extracted data from the study reports. Our primary outcome
      was prevalence of post-imaging colorectal cancer 36 months after CT colonography.
      We used random-effects meta-analysis to estimate pooled post-imaging colorectal
      cancer rates, expressed using the total number of cancers and total number of CT
      colonographies as denominators, and per 1000 person-years. This study is
      registered with PROSPERO, number CRD42016042437. FINDINGS: 2977 articles were
      screened and 12 studies were eligible for analysis. These studies reported data
      for 19 867 patients (aged 18-96 years; of 11 590 with sex data available, 6532
      [56%] were female) between March, 2002, and May, 2015. At a mean of 34 months'
      follow-up (range 3-128.4 months), CT colonography detected 643 colorectal
      cancers. 29 post-imaging colorectal cancers were subsequently diagnosed. The
      pooled post-imaging colorectal cancer rate was 4.42 (95% CI 3.03-6.42) per 100
      cancers detected, corresponding to 1.61 (1.11-2.33) post-imaging colorectal
      cancers per 1000 CT colonographies or 0.64 (0.44-0.92) post-imaging colorectal
      cancers per 1000 person-years. Heterogeneity was low (I2=0%). 17 (61%) of 28 post
      imaging colorectal cancers were attributable to perceptual error and were visible
      in retrospect. INTERPRETATION: CT colonography does not lead to an excess of post
      test cancers relative to colonoscopy within 3-5 years, and the low 5-year post
      imaging colorectal cancer rate confirms that the recommended screening interval
      of 5 years is safe. Since most post-imaging colorectal cancers arise from
      perceptual errors, radiologist training and quality assurance could help to
      reduce post-imaging colorectal cancer rates. FUNDING: St Mark's Hospital
      Foundation and the UK National Institute for Health Research via the UCL/UCLH
      Biomedical Research Centre.

PMID- 29472117
TI  - DNA methylation signature in blood does not predict calendar age in patients with
      chronic lymphocytic leukemia but may alert to the presence of disease.

PMID- 29472118
TI  - Loss of heterozygosity of MIR15A/MIR16-1, negative regulators of the
      antiapoptotic gene BCL2, is not common in odontogenic keratocysts.
AB  - OBJECTIVES: The odontogenic keratocyst (OKC) is an aggressive odontogenic cyst
      that has a high recurrence rate. Apart from PTCH1 mutations, few molecular
      alterations are described in OKCs. Low expression of microRNAs (miRNAs) miR-15a
      and/or miR-16-1 in association with increased expression of their target, Bcl-2,
      have been previously found in OKC. In humans, MIR15A and MIR16-1 are clustered at
      chromosome position 13 q14, and loss of heterozygosity (LOH) at this locus occurs
      in different tumors. We aimed to determine whether deletion at 13 q14 is a
      potential mechanism leading to miR-15a/16-1 aberrant expression in OKC. METHODS:
      Genomic DNA was extracted from 15 formalin-fixed, paraffin-embedded
      microdissected OKC cases. The polymorphic DNA markers D13S272 and D13S273 on
      chromosome 13 q14.3, around MIR15A/MIR16-1, were amplified by polymerase chain
      reaction. LOH was examined by capillary electrophoresis DNA-fragment analysis.
      RESULTS: The D13S272 marker had no LOH in 12 informative cases, whereas 2 out of
      9 informative cases (22%) had LOH at the D13S273 marker. CONCLUSIONS: An LOH
      event at MIR15A/MIR16-1 locus is not common in OKC. The mechanism underlying the
      regulation of miR-15a and miR-16-1 expression in OKC remains to be determined.

PMID- 29472119
TI  - Dupilumab treatment in moderate-to-severe atopic dermatitis: A systematic review
      and meta-analysis.
AB  - BACKGROUND: Dupilumab, a fully human monoclonal antibody against the interleukin
      4-receptor alpha subunit, has been developed and used in clinical trials to treat
      atopic dermatitis (AD). OBJECTIVE: We aimed to assess the overall efficacy and
      safety of dupilumab treatment in AD. METHODS: PubMed, Embase, Cochrane library
      databases, and the Chinese Biological Medicine (CBM) published up to September
      2017 were searched. All randomized controlled trials (RCTs) of dupilumab
      treatment on adult patients with AD were included. Fixed- or random-effects
      models were used to calculate pooled standard mean differences or relative risks
      (SMD or RR, respectively). RESULTS: Six trials involving 2447 patients were
      identified. Pooled analysis revealed significant improvements in Eczema Area and
      Severity Index (EASI) score (SMD = -0.89, 95% CI: -1.0 to -0.78), percentage of
      body surface area (BSA) (SMD = -0.83, 95% CI: -0.90 to -0.75), pruritus numeric
      rating scale (NRS) scores (SMD = -0.81, 95% CI: -0.96 to -0.66), and Dermatology
      Life Quality Index (DLQI) scores (SMD = -0.78, 95% CI: -0.89 to -0.66). Dupilumab
      treatment was also associated with a significant increase in the proportion of
      patients achieving Investigator's Global Assessment (IGA) response (RR = 3.82;
      95% CI: 3.23 to 4.51) and a similar incidence of adverse events (RR = 1.0; 95%
      CI: 0.96 to 1.04). CONCLUSIONS: Our analysis provided evidence that dupilumab had
      an acceptable safety profile and resulted in clinically relevant improvements in
      signs and symptoms of AD. Dose regimens of 300 mg qw and q2 w seemed to have
      similar benefits. Further long-term trials are required for confirmation.

PMID- 29472120
TI  - Targeting CD6 for the treatment of experimental autoimmune uveitis.
AB  - OBJECTIVE: CD6 is emerging as a new target for treating many pathological
      conditions in which T cells are integrally involved, but even the latest data
      from studies of CD6 gene engineered mice were still contradictory. To address
      this issue, we studied experimental autoimmune uveitis (EAU), a model of
      autoimmune uveitis, in wild-type (WT) and CD6 knockout (KO) mice. METHODS: After
      EAU induction in WT and CD6 KO mice, we evaluated ocular inflammation and
      compared retinal antigen-specific T-cell responses using scanning laser
      ophthalmoscopy, spectral-domain optical coherence tomography, histopathology, and
      T cell recall assays. Uveitogenic T cells from WT and CD6 KO mice were adoptively
      transferred into WT naive mice to confirm the impact of CD6 on T cells. In
      addition, we immunized CD6 KO mice with recombinant CD6 protein to develop mouse
      anti-mouse CD6 monoclonal antibodies (mAbs) in which functional antibodies
      exhibiting cross-reactivity with human CD6 were screened and identified for
      treatment studies. RESULTS: In CD6 KO mice with EAU, we found significantly
      decreased retinal inflammation and reduced autoreactive T-cell responses, and
      confirmed the impaired uveitogenic capacity of T cells from these mice in an
      adoptive transfer experiment. Notably, one of these cross-reactive mAbs
      significantly ameliorated retinal inflammation in EAU induced by the adoptive
      transfer of uveitogenic T cells. CONCLUSIONS: Together, these data strongly
      suggest that CD6 plays a previously unknown, but pivotal role in autoimmune
      uveitis, and may be a promising new treatment target for this blinding disease.
      In addition, the newly developed mouse anti-mouse/human CD6 mAbs could be
      valuable tools for testing CD6-targeted therapies in other mouse models of human
      diseases.

PMID- 29472121
TI  - The relationship between energy intake and body-growth in children with cystic
      fibrosis.
AB  - BACKGROUND & AIMS: Body-growth, expressed as weight- and height gain, is a strong
      predictor of morbidity and mortality in patients with cystic fibrosis (CF).
      Whether current historically based recommendations on a high-energy diet are
      sufficient for optimal growth is questionable. We therefore assessed the
      longitudinal relation between body-growth and routine energy intake in paediatric
      CF patients. METHODS: Included were patients with CF, aged 2-10 years of whom we
      obtained 969 measurements of weight and height along with dietary records, and
      786 coefficient of fat absorption measurements (CFA). We described body-growth,
      energy intake, macronutrient intake and the long-term effect of energy intake and
      coefficient of fat absorption on body-growth during the 8-year follow-up period.
      RESULTS: Enrolled were 191 children with CF who had a compromised growth when
      compared to healthy children. The dietary intake was >=110% estimated average
      requirement (EAR) in 47% of the measurements (457/969) and did not (fully)
      achieve the recommended high-energy level (110-200% EAR). Further, the intake
      expressed as EAR decreased with increasing age. Cross-sectionally, boys and girls
      with higher caloric intakes had higher weight-for-age (WFA). The caloric intake
      explained 18 and 6% of the variation. Further, boys with higher caloric intakes
      had also higher height-for-age-adjusted-for-target-height (HFA/TH) or BMI. The
      caloric intake explained 6 or 7% of the variation. Longitudinally, caloric intake
      was associated with both WFA in boys and girls, and with BMI in boys. Each 100
      calories increased intake would result in a 0.01 (girls)-0.02 increase in z-score
      WFA and 0.03 increase in z-score BMI. We found no significant association between
      CFA and WFA, HFA/TH or BMI. The contribution of protein, fat and carbohydrates
      was not associated with WFA, nor with HFA/TH or BMI. CONCLUSION: Even at this
      relatively early age, a compromised growth in children with CF was found when
      compared to healthy children. The energy intake was below 110% EAR in 47% of the
      measurements, and appeared to be insufficient to prevent suboptimal body-growth
      over the 8-years of follow-up.

PMID- 29472122
TI  - Recent developments of downstream processing for microbial lipids and conversion
      to biodiesel.
AB  - With increasing global population and depleting resources, there is an apparent
      demand for radical unprecedented innovation to satisfy the basal needs of lives.
      Hence, non-conventional renewable energy resources like biodiesel have been
      worked out in past few decades. Biofuel (e.g. Biodiesel) serves to be the most
      sustainable answer to solve "food vs. fuel crisis". In biorefinery process, lipid
      extraction from oleaginous microbial lipids is an integral part as it facilitates
      the release of fatty acids. Direct lipid extraction from wet cell-biomass is
      favorable in comparison to dry-cell biomass because it eliminates the application
      of expensive dehydration. However, this process is not commercialized yet,
      instead, it requires intensive research and development in order to establish
      robust approaches for lipid extraction that can be practically applied on an
      industrial scale. This review aims for the critical presentation on cell
      disruption, lipid recovery and purification to support extraction from wet cell
      biomass for an efficient transesterification.

PMID- 29472123
TI  - Can algae-based technologies be an affordable green process for biofuel
      production and wastewater remediation?
AB  - Algae is a well-known organism that its characteristic is prominent for biofuel
      production and wastewater remediation. This critical review aims to present the
      applicability of algae with in-depth discussion regarding three key aspects: (i)
      characterization of algae for its applications; (ii) the technical approaches and
      their strengths and drawbacks; and (iii) future perspectives of algae-based
      technologies. The process optimization and combinations with other chemical and
      biological processes have generated efficiency, in which bio-oil yield is up to
      41.1%. Through life cycle assessment, algae bio-energy achieves high energy
      return than fossil fuel. Thus, the algae-based technologies can reasonably be
      considered as green approaches. Although selling price of algae bio-oil is still
      high (about $2 L-1) compared to fossil fuel's price of $1 L-1, it is expected
      that the algae bio-oil's price will become acceptable in the next coming decades
      and potentially dominate 75% of the market.

PMID- 29472125
TI  - Discovery of isatin and 1H-indazol-3-ol derivatives as d-amino acid oxidase
      (DAAO) inhibitors.
AB  - d-Amino acid oxidase (DAAO) is a potential target in the treatment of
      schizophrenia as its inhibition increases brain d-serine level and thus
      contributes to NMDA receptor activation. Inhibitors of DAAO were sought testing
      [6+5] type heterocycles and identified isatin derivatives as micromolar DAAO
      inhibitors. A pharmacophore and structure-activity relationship analysis of
      isatins and reported DAAO inhibitors led us to investigate 1H-indazol-3-ol
      derivatives and nanomolar inhibitors were identified. The series was further
      characterized by pKa and isothermal titration calorimetry measurements.
      Representative compounds exhibited beneficial properties in in vitro metabolic
      stability and PAMPA assays. 6-fluoro-1H-indazol-3-ol (37) significantly increased
      plasma d-serine level in an in vivo study on mice. These results show that the 1H
      indazol-3-ol series represents a novel class of DAAO inhibitors with the
      potential to develop drug candidates.

PMID- 29472124
TI  - Design, synthesis and biological assessment of N-adamantyl, substituted adamantyl
      and noradamantyl phthalimidines for nitrite, TNF-alpha and angiogenesis
      inhibitory activities.
AB  - A library of 15 novel and heretofore uncharacterized adamantyl and noradamantyl
      phthalimidines was synthesized and evaluated for neuroprotective and anti
      angiogenic properties. Phthalimidine treatment in LPS-challenged cells effected
      reductions in levels of secreted TNF-alpha and nitrite relative to basal amounts.
      The primary SAR suggests nitration of adamantyl phthalimidines has marginal
      effect on TNF-alpha activity but promotes anti-nitrite activity; thioamide
      congeners retain anti-nitrite activity but are less effective reducing TNF-alpha.
      Site-specific nitration and thioamidation provided phthalimidine 24, effecting an
      88.5% drop in nitrite concurrent with only a 4% drop in TNF-alpha. Notable anti
      angiogenesis activity was observed for 20, 21 and 22.

PMID- 29472126
TI  - Development of benzoxazole deoxybenzoin oxime and acyloxylamine derivatives
      targeting innate immune sensors and xanthine oxidase for treatment of gout.
AB  - Both the inhibition of inflammatory flares and the treatment of hyperuricemia
      itself are included in the management of gout. Extending our efforts to
      development of gout therapy, two series of benzoxazole deoxybenzoin oxime
      derivatives as inhibitors of innate immune sensors and xanthine oxidase (XOD)
      were discovered in improving hyperuricemia and acute gouty arthritis. In vitro
      studies revealed that most compounds not only suppressed XOD activity, but
      blocked activations of NOD-like receptor (NLRP3) inflammasome and Toll-like
      receptor 4 (TLR4) signaling pathway. More importantly, (E)-1-(6
      methoxybenzo[d]oxazol-2-yl)-2-(4-methoxyphenyl)ethanone oxime (5d) exhibited anti
      hyperuricemic and anti-acute gouty arthritis activities through regulating XOD,
      NLRP3 and TLR4. Compound 5d may serve as a tool compound for further design of
      anti-gout drugs targeting both innate immune sensors and XOD.

PMID- 29472127
TI  - Synthesis of S-linked NeuAc-alpha(2-6)-di-LacNAc bearing liposomes for H1N1
      influenza virus inhibition assays.
AB  - S-NeuAc-alpha(2-6)-di-LacNAc (5) was efficiently synthesized by a [2+2] followed
      by a [1+4] glycosylation, and later conjugated with 1,2-dilauroyl-sn-glycero-3
      phosphoethanolamine (DLPE) to form both single-layer and multi-layer homogeneous
      liposomes in the presence of dipalmitoyl phosphatidylcholine (DPPC) and
      cholesterol. These liposomes were found to be weak inhibitors in both the
      influenza virus entry assay and the hemagglutination inhibition assay. The single
      layer liposome was found to more efficiently interfere with the entry of the H1N1
      influenza virus into MDCK cells than the multilayer liposome containing 5.

PMID- 29472128
TI  - Educating and Training the Future Adolescent Health Workforce.
AB  - Unprecedented attention is now focused on adolescents with growing appreciation
      of their disease burden and of the opportunities of investing in adolescent
      health. New investments are required to build the technical capacity for policy,
      programming, research, and clinical care across the world, especially in resource
      poor settings where most adolescents live. Strategies to educate and train the
      future workforce are needed. Competency-based education and training is the
      standard of education in preservice (undergraduate and postgraduate) health
      education and medical specialty training. Yet competency is difficult to quantify
      and standardize, as are the processes that underpin competency-based education
      and training. The primary objective of this review was to identify how quality
      education in adolescent health and medicine is determined. This information was
      used to inform the development of a conceptual framework for institutions
      teaching adolescent health, which can be used to assess the quality of teaching
      and learning and to monitor the implementation of these adolescent health
      competencies. Specific teaching modalities and assessment tools that have been
      used to teach adolescent health are described to exemplify how an educational
      program can be delivered and assessed. This framework is a step toward the
      development of a more adolescent-competent health workforce.

PMID- 29472129
TI  - Reduced variability of visual left ventricular ejection fraction assessment with
      reference images: The Japanese Association of Young Echocardiography Fellows
      multicenter study.
AB  - BACKGROUND: Visual estimation of left ventricular ejection fraction (LVEF) is
      widely applied to confirm quantitative EF. However, visual assessment is
      subjective, and variability may be influenced by observer experience. We
      hypothesized that a learning session might reduce the misclassification rate.
      METHODS: Protocol 1: Visual LVEFs for 30 cases were measured by 79 readers from
      13 cardiovascular tertiary care centers. Readers were divided into 3 groups by
      their experience: limited (1-5 years, n=28), intermediate (6-11 years, n=26), and
      highly experienced (12-years, n=25). Protocol 2: All readers were randomized to
      assess the effect of a learning session with reference images only or feedback
      plus reference images. After the session, 20 new cases were shown to all readers
      following the same methodology. To assess the concordance and accuracy pre- and
      post-intervention, each visual LVEF measurement was compared to overall average
      values as a reference. RESULTS: Experience affected the concordance in visual EF
      values among the readers. Groups with intermediate and high experience showed
      significantly better mean difference (MD), standard deviation (SD), and
      coefficient of variation (CV) than those with limited experience at baseline. The
      learning session with reference image reduced the MD, SD, and CV in readers with
      limited experience. The learning session with reference images plus feedback also
      reduced proportional bias. Importantly, the misclassification rate for mid-range
      EF cases was reduced regardless of experience. CONCLUSION: This large multicenter
      study suggested that a simple learning session with reference images can
      successfully reduce the misclassification rate for LVEF assessment.

PMID- 29472130
TI  - Zinc in soils, water and food crops.
AB  - A basic knowledge of the dynamics of zinc (Zn) in soils, water and plants are
      important steps in achieving sustainable solutions to the problem of Zn
      deficiency in crops and humans. This paper aims at reviewing and discussing the
      relevant aspects of the role of Zn in the soil-water-plant agro biological
      system: from the origins of Zn in soils and water to soil Zn deficiency
      distribution and the factors affecting soil Zn availability to plants, therefore
      to elucidate the strategies potentially help combating Zn deficiency problems in
      soil-plant-human continuum. This necessitates identifying the main areas of Zn
      deficient soils and food crops and treating them with Zn amendments, mainly
      fertilizers in order to increase Zn uptake and Zn use efficiency to crops. In
      surface and groundwater, Zn enters the environment from various sources but
      predominately from the erosion of soil particles containing Zn. In plants is
      involved in several key physiological functions (membrane structure,
      photosynthesis, protein synthesis, and drought and disease tolerance) and is
      required in small but nevertheless critical contents. Several high revenue food
      crops such as beans, citrus, corn, rice etc are highly susceptible to Zn
      deficiency and biofortification is considered as a promising method to accumulate
      high content of Zn especially in grains. With the world population continuing to
      rise and the problems of producing extra food rich in Zn to provide an adequate
      standard of nutrition to increase, it is very important that any losses in
      production easily corrected so as Zn deficiencies are prevented.

PMID- 29472131
TI  - Species fractionation in a case-control study concerning Parkinson's disease: Cu
      amino acids discriminate CSF of PD from controls.
AB  - BACKGROUND: Parkinson's disease is affecting about 1% of the population above 65
      years. Improvements in medicine support prolonged lifetime which increases the
      total concentration of humans affected by the disease. It is suggested that
      occupational and environmental exposure to metals like iron (Fe), manganese (Mn),
      copper (Cu) and zinc (Zn) can influence the risk for Parkinson's disease. These
      metals play a key role as cofactors in many enzymes and proteins. METHODS: In
      this case-control study, we investigated the Mn-, Fe-, Cu- and Zn-species in
      cerebrospinal fluid (CSF) by size-exclusion chromatography hyphenated to
      inductively coupled plasma mass spectrometry (SEC-ICP-MS) and the total
      concentration of these metals by inductively coupled plasma sector field mass
      spectrometry (ICP-sf-MS). RESULTS: The investigation of total metal concentration
      and speciation provided only minor changes, but it produced strong significance
      for a number of ratios. The analysis revealed a strong change in the ratio
      between total concentration of Fe and the amino acid-fraction of Cu. This could
      be observed when analyzing both the respective element concentrations of the
      fraction (which also depends on individual variation of the total element
      concentration) as well as when being expressed as percentage of total
      concentration (normalization) which more clearly shows changes of distribution
      pattern independent of individual variation of total element concentrations.
      CONCLUSION: Speciation analysis, therefore, is a powerful technique to
      investigate changes in a case-control study where ratios of different species
      play an important role.

PMID- 29472133
TI  - Vaccine safety testing using magnetic resonance imaging in suckling pigs.
AB  - Safety testing is one major part of the licensing procedure for veterinary
      vaccines and demands a large number of animals. Magnetic resonance imaging (MRI)
      was tested as an alternative, which may lead to a reduction in numbers of animals
      required for safety testing, and, correspondingly to a detailed description of
      the three-dimensional extent of the local tissue reaction repetitively in live
      pigs. In previous pig studies the following questions arose:To answer these
      questions the following study was performed by comparing two vaccine groups of
      suckling piglets (8 animals per group; A and B) with two control groups (4
      animals per group; C and D). One control group was injected with a saline
      solution (C) and the other was only tattoo marked (D). The animals were examined
      using MRI at days 1, 8, 15, 22, 29, 36, and 43 post vaccination, ending with a
      final pathomorphologic examination. Pathomorphologic examination confirmed MRI
      findings. Saline solution does not result in a local tissue reaction as detected
      after injecting vaccines. Tattoo marking causes no local tissue reaction, neither
      in MRI nor in pathomorphologic examination. Therefore, MRI can be used as an
      alternative method for safety testing of vaccines in pigs of different age
      categories offering repetitive measurements of local tissue reactions. Involved
      cells might be examined only in a final pathomorphologic examination at the end
      of the trial on a reduced number of animals.

PMID- 29472134
TI  - Disruption of cortical synaptic homeostasis in individuals with chronic low back
      pain.
AB  - OBJECTIVE: Homeostatic plasticity mechanisms regulate synaptic plasticity in the
      human brain. Impaired homeostatic plasticity may contribute to maladaptive
      synaptic plasticity and symptom persistence in chronic musculoskeletal pain.
      METHODS: We examined homeostatic plasticity in fifty individuals with chronic low
      back pain (cLBP) and twenty-five pain-free controls. A single block (7-min) of
      anodal transcranial direct current stimulation ('single tDCS'), or two subsequent
      blocks (7-min and 5-min separated by 3-min rest; 'double tDCS'), were randomised
      across two experimental sessions to confirm an excitatory response to tDCS
      applied alone, and evaluate homeostatic plasticity, respectively. Corticomotor
      excitability was assessed in the corticomotor representation of the first dorsal
      interosseous muscle by transcranial magnetic stimulation-induced motor evoked
      potentials (MEPs) recorded before and 0, 10, 20, and 30-min following each tDCS
      protocol. RESULTS: Compared with baseline, MEP amplitudes increased at all time
      points in both groups following the single tDCS protocol (P < 0.003). Following
      the double tDCS protocol, MEP amplitudes decreased in pain-free controls at all
      time points compared with baseline (P < 0.01), and were unchanged in the cLBP
      group. CONCLUSION: These data indicate impaired homeostatic plasticity in the
      primary motor cortex of individuals with cLBP. SIGNIFICANCE: Impaired homeostatic
      plasticity could explain maladaptive synaptic plasticity and symptom persistence
      in cLBP.

PMID- 29472132
TI  - Efficacy of a high quality O1/Campos foot-and-mouth disease vaccine upon
      challenge with a heterologous Korean O Mya98 lineage virus in pigs.
AB  - In 2010 serotype O foot-and-mouth disease virus of the Mya98 lineage/SEA topotype
      spread into most East Asian countries. During 2010-2011 it was responsible for
      major outbreaks in the Republic of Korea where a monovalent O/Manisa vaccine
      (belonging to the ME-SA topotype) was applied to help control the outbreaks.
      Subsequently, all susceptible animals were vaccinated every 6 months with a
      vaccine containing the O/Manisa antigen. Despite vaccination, the disease re
      occurred in 2014 and afterwards almost annually. This study focuses on the in
      vivo efficacy in pigs of a high quality monovalent commercial O1/Campos vaccine
      against heterologous challenge with a representative 2015 isolate from the
      Jincheon Province of the Republic of Korea. Initially, viral characterizations
      and r1 determinations were performed on six viruses recovered in that region
      during 2014-2015, centering on their relationship with the well characterized and
      widely available O1/Campos vaccine strain. Genetic and antigenic analysis
      indicated a close similarity among 2014-2015 Korean isolates and with the
      previous 2010 virus, with distinct differences with the O1/Campos strain. Virus
      neutralisation tests using O1/Campos cattle and pig post vaccination sera and
      recent Korean outbreak viruses predicted acceptable cross-protection after a
      single vaccination, as indicated by r1 values, and in pigs, by expectancy of
      protection. In agreement with the in vitro estimates, in vivo challenge with a
      selected field isolate indicated that O1/Campos primo vaccinated pigs were
      protected, resulting in a PD50 value of nearly 10. The results indicated that
      good quality oil vaccines containing the O1/Campos strain can successfully be
      used against isolates belonging to the O Mya98/SEA topotype.

PMID- 29472135
TI  - Reply to "10-10 electrode system for EEG recording".

PMID- 29472136
TI  - A field-based characterization of conductivity in areas of minimal alteration: A
      case example in the Cascades of northwestern United States.
AB  - The concentration of salts in streams is increasing world-wide making freshwater
      a declining resource. Developing thresholds for freshwater with low specific
      conductivity (SC), a measure of dissolved ions in water, may protect high quality
      resources that are refugia for aquatic life and that dilute downstream waters. In
      this case example, methods are illustrated for estimating protective levels for
      streams with low SC. The Cascades in the Pacific Northwest of the United States
      of America was selected for the case study because a geophysical model indicated
      that the SC of freshwater streams was likely to be very low. Also, there was an
      insufficient range in the SC data to accurately derive a criterion using the
      2011, US Environmental Protection Agency field-based extirpation concentration
      distribution method. Instead, background and a regression model was used to
      estimate chronic and acute SC levels that could extirpate 5% of benthic
      invertebrate genera. Background SC was estimated at the 25th centile (33MUS/cm)
      of the measured data and used as the independent variable in a least squares
      empirical background-to-criteria (B-C) model. Because no comparison could be made
      with effect levels estimated from a paired SC and biological data set from the
      Cascades, the lower 50% prediction limit (PL) was identified as an example
      chronic water quality criterion (97MUS/cm). The maximum exposure threshold was
      estimated at the 90th centile SC of streams meeting the chronic SC level. The
      example acute SC level was 190MUS/cm. Because paired aquatic life and SC data are
      often sparse, the B-C method is useful for developing SC criteria for other
      systems with limited data.

PMID- 29472137
TI  - Synthesis of steroid hormones in the porcine oviduct during early pregnancy.
AB  - Past studies of the oviducts have documented oviductal steroid production during
      the oestrous cycle in pigs. The present study examined whether the pig oviducts
      are the source of steroid hormones during early pregnancy. In the ampulla and
      isthmus, the expression of 3beta-hydroxysteroid dehydrogenase (3betaHSD) and
      aromatase cytochrome P450 (CYP19) mRNA by real-time PCR, cellular localization
      and quantities of the studied proteins by immunofluorescence and Western blot
      analysis, and concentration of steroid hormones in oviductal flushings by
      radioimmunoassay, were studied. The expression of 3betaHSD in the ampulla and
      isthmus was correlated (r = 0.89) and higher on Days 2-3 and 15-16 than on Days
      10-11 and 12-13. CYP19 expression was elevated in the ampulla on Days 2-3, 10-11
      and 15-16 and in the isthmus on Days 2-3 vs. the other days studied. The studied
      proteins were localized in oviductal epithelial cells. In the ampulla, the
      quantity of 3betaHSD protein did not change, and was greater in the isthmus on
      Days 2-3 vs. Days 12-13 of pregnancy. The P450arom protein quantity increased in
      the ampulla on Days 2-3 vs. Days 10-11 and 15-16 and vs. Days 10-11 and 12-13 in
      the isthmus. The concentrations of progesterone and androstenedione in oviductal
      flushings were lowest on Days 12-13 and on Days 2-3 and 15-16, respectively,
      while oestradiol-17beta and oestrone levels did not change. Porcine oviducts are
      the sources of steroid hormones during early pregnancy. The expression of
      steroidogenic enzymes primarily increases during the embryos presence in the
      oviduct, i.e., on Days 2-3 of pregnancy.

PMID- 29472138
TI  - Understanding the underlying motives and intention among Indian blood donors
      towards voluntary blood donation: A cross-sectional study.
AB  - OBJECTIVES: The present study aims to fill the gap in the literature by
      conducting a comprehensive research on Indian donor's intention towards voluntary
      blood donation in India. The study attempts to conceptualize and validate an
      integrative framework incorporating voluntary function inventory (VFI) in the
      theory of planned behaviour (TPB) model with the purpose tomeasure the voluntary
      blood donation intention. MATERIAL AND METHODS: Structural equation modeling
      (SEM) has been used to rigorously test the hypothesized interrelationships among
      the underlying motives influencing voluntary blood donation intention. A self
      administered questionnaire was used to collect data from a sample of respondents
      selected conveniently from selct locations in India. Total 450 completed
      questionnaires were received out of 1000 distributed. RESULTS: The study develops
      a final conceptual framework that determines the drivers of blood donor's
      intention towards voluntary donation. The components of theory of planned
      behavior (TPB) model which include 'attitude', 'subjective norms' (SN), and
      'perceived behavioral control' (PBC) along with modified volunteer functions
      namely 'value', 'social', 'career' and 'enhancement' were found significantly
      explaining the donation intention in the model. CONCLUSION: The model achieves
      robustness with respect to predicting Indian donor's intention towards the
      voluntary donation of blood. The proposed model in this study advances the theory
      and research on thevolunteering motives towards blood donation. The study would
      provide a comprehensiveunderstanding of donors' intention to the practitioners,
      policy makers and Non-Government Organization (NGO), helping them to frame a
      calibrated strategydirected towards facilitating healthy blood donation
      practices.

PMID- 29472139
TI  - Amplitude-integrated electroencephalography for seizure detection in newborn
      infants.
AB  - The amplitude-integrated electroencephalogram (aEEG) is a filtered and compressed
      EEG trend that can be used for long-term monitoring of brain function in patients
      of all ages. aEEG is increasingly used in neonatal intensive care units since
      several studies have shown its utility in high-risk newborn infants. Main
      indications for aEEG monitoring include early evaluation of brain function after
      perinatal asphyxia and seizure detection. The aEEG is usually recorded from one
      or two channels derived from parietal, central, or frontal leads. Although the
      aEEG is very useful for identifying high-risk infants and infants with seizures,
      the compressed trend has limitations with regards to detection of individual
      seizures. However, modern monitors also display the corresponding EEG (aEEG/EEG),
      which increases the probability of detecting single brief seizures. For improved
      evaluation of electrocortical brain activity the aEEG/EEG should be assessed
      together with repeated conventional EEGs or multi-channel EEG monitoring in a
      multi-disciplinary team.

PMID- 29472140
TI  - Hemolytic strains of Propionibacterium acnes do not demonstrate greater
      pathogenicity in periprosthetic shoulder infections.
AB  - BACKGROUND: Hemolysis has been suggested as a feature conferring increased
      pathogenicity to certain Propionibacterium acnes strains in the setting of
      shoulder infection. The purpose of this study was to compare the virulence of
      hemolytic and nonhemolytic P acnes strains in patients undergoing revision
      shoulder arthroplasty. METHODS: Thirty-nine patients with at least 1 positive
      culture growth for P acnes at the time of revision surgery were identified with P
      acnes isolates available for hemolysis testing. Patients were grouped into those
      with P acnes isolates positive (n = 20) and negative (n = 19) for hemolysis. The
      groups were retrospectively compared based on objective perioperative findings
      around the time of revision surgery and the postoperative clinical course,
      including the need for revision surgery. All cases were classified into
      categories of infection (definite infection, probable infection, and probable
      contaminant) based on objective perioperative criteria. RESULTS: The presence of
      hemolysis was not significantly associated with an increased likelihood of
      infection (P = .968). Hemolysis demonstrated a 75% sensitivity and 26%
      specificity for determining infection (definite infection and probable infection
      categories). The hemolytic and nonhemolytic groups showed no difference regarding
      preoperative serum erythrocyte sedimentation rate and/or C-reactive protein level
      (P = .70), number of positive cultures (P = .395), time to positive culture (P =
      .302), and presence of positive frozen section findings (P = .501).
      Postoperatively, clindamycin resistance, shoulder function, and the rate of
      reoperation were not significantly different between the hemolytic and
      nonhemolytic groups. CONCLUSION: The presence of hemolysis was not associated
      with increased pathogenicity in patients with P acnes-positive cultures following
      revision shoulder arthroplasty, when assessed by objective perioperative criteria
      and the postoperative clinical course.

PMID- 29472141
TI  - T cell deficiencies as a common risk factor for drug associated progressive
      multifocal leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy (PML) is a disease of the central
      nervous system caused by neuropathogenic prototypes of ubiquitous community
      acquired JC virus (JCV). The disease became of particular concern following its
      association with certain therapies that modulate immune system function without
      heavy immunosuppression. Due to lack of prophylactic/treatment options and poor
      outcomes, which often include severe disability or death, PML is a considerable
      concern for development of new drugs that interfere with immune system functions.
      In this review of clinical and research findings, we discuss the evidence that
      deficiencies in CD4+ T helper cells, cytotoxic CD8+ T cells, and interferon gamma
      are of crucial importance for development of PML under a variety of
      circumstances, including those associated with use of various drugs, regardless
      of differences in their mechanisms of action. These deficiencies apparently
      enable transformation of the harmless JCV archetype into neuropathogenic
      prototypes, but the site(s), and the mechanisms, of this transformation are yet
      to be elucidated. Here we discuss the evidence for brain as one of the sites of
      this transformation, and propose a model of PML pathogenesis that emphasizes the
      central role of T cell deficiencies in the two life cycles of the JCV, one non
      pathogenic and one neuropathogenic. Finally, we conclude that the development of
      clinical grade T cell functional tests and more consistent use of already
      available laboratory tests for T cell subset analysis would greatly aid the
      effort to more accurately predict and assess the magnitude of PML risk for
      concerned therapeutic interventions.

PMID- 29472142
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- 29472143
TI  - Safety of Vaginal Mesh Surgery Versus Laparoscopic Mesh Sacropexy for Cystocele
      Repair: Results of the Prosthetic Pelvic Floor Repair Randomized Controlled
      Trial.
AB  - BACKGROUND: Laparoscopic mesh sacropexy (LS) or transvaginal mesh repair (TVM)
      are surgical techniques used to treat cystoceles. Health authorities have
      highlighted the need for comparative studies to evaluate the safety of surgeries
      with meshes. OBJECTIVE: To compare the rate of complications, and functional and
      anatomical outcomes between LS and TVM. DESIGN, SETTING, AND PARTICIPANTS:
      Multicenter randomized controlled trial from October 2012 to April 2014 in 11
      French public hospitals. Women with cystocele stage >=2 (pelvic organ prolapse
      quantification), aged 45-75 yr, without previous prolapse surgery. INTERVENTION:
      Synthetic nonabsorbable mesh placed in the vesicovaginal space, sutured to the
      promontory (LS) or maintained by arms through pelvic ligaments (TVM). OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Rate of surgical complications >=grade II
      according to the modified Clavien-Dindo classification at 1 yr. Secondary
      outcomes were reintervention rate, and functional and anatomical results. RESULTS
      AND LIMITATIONS: A total of 130 women were randomized in LS and 132 in TVM; five
      women withdrew before intervention, leaving 129 in LS and 128 in TVM. The rate of
      complications >=grade II was lower after LS than after TVM, but did not meet
      statistical significance (17% vs 26%, treatment difference 8.6% [95% confidence
      interval, CI -1.5 to 18]; p=0.088). The rate of complications of grade III or
      higher was nonetheless significantly lower after LS (LS=0.8%, TVM=9.4%, treatment
      difference 8.6% [95% CI 3.4%; 15%]; p=0.001). LS was converted to TVM in 6.3%.
      The total reoperation rate was lower after LS but did not meet statistical
      significance (LS=4.7%, TVM=10.9%, treatment difference 6.3% [95% CI -0.4 to
      13.3]; p=0.060). There was no difference in symptoms, quality of life,
      improvement, composite definition of success, anatomical results rates between
      groups except for the vaginal apex and length, and dyspareunia (in favor of LS).
      CONCLUSIONS: LS is a valuable option for primary repair of cystocele in sexually
      active patients. LS is safer than TVM, but may not be feasible in all cases. Both
      techniques offer same functional outcomes, success rates, and anatomical
      outcomes, but sexual function is better preserved by LS. PATIENT SUMMARY: Our
      study demonstrates that laparoscopic sacropexy (LS) is a valuable option for
      primary repair of cystocele. LS offers equivalent success rates to vaginal mesh
      procedures, but is safer with a lower rate of complications and reoperations, and
      sexual function is better preserved.

PMID- 29472144
TI  - Is 68Ga-Prostate-specific Membrane Antigen-ligand Positron Emission
      Tomography/Computed Tomography Ready To Simplify the Conundrum of Biochemically
      Recurrent Prostate Cancer?

PMID- 29472145
TI  - Decreased hemodynamic response in inferior frontotemporal regions in elderly with
      mild cognitive impairment.
AB  - The verbal fluency task (VFT) is a well-established cognitive marker for mild
      cognitive impairment (MCI) in the prodromal stage of Alzheimer's dementia (AD).
      The behavioral VFT performance of patients allows the prediction of dementia two
      years later. But effective compensatory mechanism might cover or reduce the
      predictive value of the VFT. Therefore the aim of this study is to measure the
      hemodynamic response during VFT in patients with mild cognitive impairment (MCI)
      to establish the hemodynamic response during the VFT as a screening instrument
      for the prediction of dementia. One method which allows measuring the hemodynamic
      response during speech production without severe problems with moving artifacts
      like in functional magnetic resonance imaging (fMRI) is the functional near
      infrared spectroscopy (fNIRS). It is optimal as a screening instrument, as it is
      easy to apply and without any contraindications. In this study we assessed the
      hemodynamic response in prefrontal and temporal regions in patients with MCI as
      well as matched healthy controls with fNIRS. We found a decreased hemodynamic
      response in the inferior frontotemporal cortex for the MCI group. Our results
      indicate that a frontotemporal decreased hemodynamic response could serve as a
      diagnostic biomarker for dementia.

PMID- 29472146
TI  - Machine Learning Algorithms Utilizing Quantitative CT Features May Predict
      Eventual Onset of Bronchiolitis Obliterans Syndrome After Lung Transplantation.
AB  - RATIONALE AND OBJECTIVES: Long-term survival after lung transplantation (LTx) is
      limited by bronchiolitis obliterans syndrome (BOS), defined as a sustained
      decline in forced expiratory volume in the first second (FEV1) not explained by
      other causes. We assessed whether machine learning (ML) utilizing quantitative
      computed tomography (qCT) metrics can predict eventual development of BOS.
      MATERIALS AND METHODS: Paired inspiratory-expiratory CT scans of 71 patients who
      underwent LTx were analyzed retrospectively (BOS [n = 41] versus non-BOS [n =
      30]), using at least two different time points. The BOS cohort experienced a
      reduction in FEV1 of >10% compared to baseline FEV1 post LTx. Multifactor
      analysis correlated declining FEV1 with qCT features linked to acute inflammation
      or BOS onset. Student t test and ML were applied on baseline qCT features to
      identify lung transplant patients at baseline that eventually developed BOS.
      RESULTS: The FEV1 decline in the BOS cohort correlated with an increase in the
      lung volume (P = .027) and in the central airway volume at functional residual
      capacity (P = .018), not observed in non-BOS patients, whereas the non-BOS cohort
      experienced a decrease in the central airway volume at total lung capacity with
      declining FEV1 (P = .039). Twenty-three baseline qCT parameters could
      significantly distinguish between non-BOS patients and eventual BOS developers (P
      < .05), whereas no pulmonary function testing parameters could. Using ML methods
      (support vector machine), we could identify BOS developers at baseline with an
      accuracy of 85%, using only three qCT parameters. CONCLUSIONS: ML utilizing qCT
      could discern distinct mechanisms driving FEV1 decline in BOS and non-BOS LTx
      patients and predict eventual onset of BOS. This approach may become useful to
      optimize management of LTx patients.

PMID- 29472148
TI  - The man whose head expanded.

PMID- 29472147
TI  - Phosphoinositide 3-kinase pathways and autophagy require phosphatidylinositol
      phosphate kinases.
AB  - Phosphatidylinositol phosphate kinases (PIPKs) generate a lipid messenger
      phosphatidylinositol 4,5-bisphosphate (PI4,5P2) that controls essentially all
      aspects of cellular functions. PI4,5P2 rapidly diffuses in the membrane of the
      lipid bilayer and does not greatly change in membrane or cellular content, and
      thus PI4,5P2 generation by PIPKs is tightly linked to its usage in subcellular
      compartments. Based on this verity, recent study of PI4,5P2 signal transduction
      has been focused on investigations of individual PIPKs and their underlying
      molecular regulation of cellular processes. Here, we will discuss recent advances
      in the study of how PIPKs control specific cellular events through assembly and
      regulation of PI4,5P2 effectors that mediate specific cellular processes. A focus
      will be on the roles of PIPKs in control of the phosphoinositide 3-kinase pathway
      and autophagy.

PMID- 29472149
TI  - The Effect of Parkinson Disease Tremor Phenotype on Cepstral Peak Prominence and
      Transglottal Airflow in Vowels and Speech.
AB  - OBJECTIVES: The physiological manifestations of Parkinson disease are
      heterogeneous, as evidenced by disease subtypes. Dysphonia has been well
      documented as an early and progressively significant impairment associated with
      the disease. The purpose of this study was to investigate how acoustic and
      aerodynamic measures of vocal function were affected by Parkinson tremor subtype
      (phenotype) in an effort to better understand the heterogeneity of voice
      impairment severity in Parkinson disease. STUDY DESIGN: This is a prospective
      case-control study. METHODS: Thirty-two speakers with Parkinson disease assigned
      to tremor and nontremor phenotypes and 10 healthy controls were recruited.
      Sustained vowels and connected speech were recorded from each speaker. Acoustic
      measures of cepstral peak prominence (CPP) and aerodynamic measures of
      transglottal airflow (TAF) were calculated from the recorded acoustic and
      aerodynamic waveforms. RESULTS: Speakers with a nontremor dominant phenotype
      exhibited significantly (P < 0.05) lower CPP and higher TAF in vowels compared
      with the tremor dominant phenotype and control speakers, who were not different
      from each other. No significant group differences were observed for CPP or TAF in
      connected speech. CONCLUSIONS: When producing vowels, participants with nontremor
      dominant phenotype exhibited reduced phonation periodicity and elevated TAF
      compared with tremor dominant and control participants. This finding is
      consistent with differential limb-motor and cognitive impairments between tremor
      and nontremor phenotypes reported in the extant literature. Results suggest that
      sustained vowel production may be sensitive to phonatory control as a function of
      Parkinson tremor phenotype in mild to moderate stages of the disease.

PMID- 29472150
TI  - Cost Analysis of Channeled, Distal Chip Laryngoscope for In-office
      Laryngopharyngeal Biopsies.
AB  - OBJECTIVE: Given that financial considerations play an increasingly prominent
      role in clinical decision-making, we sought (1) to determine the cost
      effectiveness of in-office biopsy for the patient, the provider, and the health
      care system, and (2) to determine the diagnostic accuracy of in-office biopsy.
      STUDY DESIGN: Retrospective, financial analyses were performed. METHODS: Patients
      who underwent in-office (Current Procedural Terminology Code 31576) or operative
      biopsy (CPT Code 31535) for laryngopharyngeal lesions were included. Two
      financial analyses were performed: (1) the average cost of operating room (OR)
      versus in-office biopsy was calculated, and (2) a break-even analysis was
      calculated to determine the cost-effectiveness of in-office biopsy for the
      provider. In addition, the diagnostic accuracy of in-office biopsies and need for
      additional biopsies or procedures was recorded. RESULTS: Of the 48 patients
      included in the current study, 28 underwent in-office biopsy. A pathologic sample
      was obtained in 26 of 28 (92.9%) biopsies performed in the office. Of these
      patients, 16 avoided subsequent OR procedures. The average per patient cost was
      $7000 and $11,000 for in-office and OR biopsy, respectively. Break-even analysis
      demonstrated that the provider could achieve a profit 2 years after purchase of
      the necessary equipment. CONCLUSION: In-office laryngopharyngeal biopsies are
      accurate and, overall, more cost-effective than OR biopsies. Purchase of the
      channeled, distal chip laryngoscope and biopsy forceps to perform in-office
      biopsies can be profitable for a provider with a videolaryngoscopy tower. In
      office biopsy should be considered the initial diagnostic tool for suspected
      laryngopharyngeal malignancies noted on videolaryngoscopy.

PMID- 29472151
TI  - Evaluation of the biodegradability and toxicity of landfill leachates after
      pretreatment using advanced oxidative processes.
AB  - Leachate from urban solid waste landfills is a complex mixture of organic and
      inorganic substances that cause damage to the environment, due to the high
      concentration of recalcitrant organic matter and toxicity. The objective of this
      study was to apply advanced oxidation processes (AOP), namely the dark Fenton and
      solar photo-Fenton processes, to young and old landfill leachates prior to
      biological treatment. The leachates were obtained from the Seropedica and
      Gramacho landfill sites, respectively, located in Rio de Janeiro State, Brazil.
      For the two Fenton processes, different conditions of pH (1.5, 3.0 and 5.0) and
      Fe2+: H2O2 ratio (1:2, 1:5 and 1:10) were evaluated. Biodegradability was
      evaluated using the Zahn-Wellens methodology and Aliivibrio fischeri acute
      toxicity tests were conducted in order to predict the toxicity in the activated
      sludge. The best conditions for both Fenton processes were pH of 3.0 and Fe2+:
      H2O2 and CODRAW:H2O2 mass ratios of 1:5 and 1:1, respectively. The solar photo
      Fenton process was more effective at improving the quality for both leachates,
      reaching COD, TOC and abs 254 nm reductions of 82%, 85% and 96.3%, respectively,
      for the Seropedica landfill leachate. In the case of the Gramacho landfill
      leachate, the corresponding reductions were 78.2, 80.7% and 91.1%, respectively.
      The biodegradability results for the untreated leachates from the Seropedica and
      Gramacho sites were 65% and 30% respectively. The biodegradability of both
      leachates was improved by the Fenton processes, especially the solar photo-Fenton
      process, which increased the leachate biodegradability to 89% (Seropedica) and
      69% (Gramacho). For both leachates, a greater reduction in the acute toxicity was
      achieved with the solar photo-Fenton compared to the dark-Fenton process. The
      Seropedica landfill leachate showed high toxicity (EC50 = 33%, 15 min), after the
      dark Fenton and solar photo Fenton processes, with EC50 values of 81 and 91%,
      respectively. In the case of Gramacho landfill leachate toxicity, the EC50 value
      of the raw leachate was 13%, whereas after the dark Fenton and solar photo Fenton
      processes the corresponding values were 54% and 59%, respectively. These results
      indicate that the Fenton process (especially solar photo-Fenton), was efficient
      in terms of increasing the biodegradability and reducing the toxicity of the
      leachate. This is important in relation to protecting the microbiological
      community in the activated sludge process.

PMID- 29472152
TI  - Designing and verifying a disassembly line approach to cope with the upsurge of
      end-of-life vehicles in China.
AB  - An upsurge of end-of-life vehicles (ELVs) is emerging in China, which means a
      potential monumental environmental crisis. The approach of disassembly line is
      expected to be an effective solution to such increasing volumes. Due to the
      complexity of vehicle product and uncertainties of disassembly processes, a
      complete set of disassembly line system should be taken into detailed
      consideration. We have designed and constructed a novel disassembly line using a
      flexible transition technique with the objective of complete disassembly. Prior
      to productivity testing, comparative Arena-based simulations on four scenarios
      have been performed and finally a best scenario is selected. The results show
      that the guarantee of cycle time is the key to meet the productivity target of
      30,000 vehicles for one year. To achieve it, some constructive measures such as
      forcible entry tools are given.

PMID- 29472153
TI  - Global status of recycling waste solar panels: A review.
AB  - With the enormous growth in the development and utilization of solar-energy
      resources, the proliferation of waste solar panels has become problematic. While
      current research into solar panels has focused on how to improve the efficiency
      of the production capacity, the dismantling and recycling of end-of-life (EOL)
      panels are seldom considered, as can be seen, for instance, in the lack of
      dedicated solar-panel recycling plants. EOL solar-panel recycling can effectively
      save natural resources and reduce the cost of production. To address the
      environmental conservation and resource recycling issues posed by the huge amount
      of waste solar panels regarding environmental conservation and resource
      recycling, the status of the management and recycling technologies for waste
      solar panels are systemically reviewed and discussed in this article. This review
      can provide a quantitative basis to support the recycling of PV panels, and
      suggests future directions for public policy makers. At present, from the
      technical aspect, the research on solar panel recovery is facing many problems,
      and we need to further develop an economically feasible and non-toxic technology.
      The research on solar photovoltaic panels' management at the end of life is just
      beginning in many countries, and there is a need for further improvement and
      expansion of producer responsibility.

PMID- 29472154
TI  - Treatment-related hemophagocytic lymphohistiocytosis secondary to checkpoint
      inhibition with nivolumab plus ipilimumab.

PMID- 29472155
TI  - The 'WiFi' otoplasty : Combined concentric posterior microchondrectomies and
      sutures for correction of prominent ears.
AB  - BACKGROUND: Prominent ears are by far the most common congenital ear deformity.
      Many techniques have been described using one or a combination of 3 basic
      methods: cartilage cutting, cartilage weakening and pure cartilage shaping
      techniques. The ideal otoplasty technique should yield a natural correction of
      the deformity, with low recurrence rates and with little risk of complications.
      METHODS: A new cartilage shaping technique using closing wedge concentric
      microchondrectomies through an entirely posterior approach is presented. Between
      2006 and 2017, 200 bilateral otoplasties using this 'WiFi' pattern technique were
      performed. This technique combined with Mustarde sutures is based on the excision
      of concentric partial thickness cartilage wedges designed in the pattern of the
      WiFi symbol. RESULTS: There were no major complications such as anterior skin
      necrosis and no returns to theatre for infections or haematomas. 3 patients
      (1.5%) had complete recurrence of the deformity and 10 patients (5%) had to
      undergo a minor revision for recurrence at the upper pole. 5 patients have had
      exposure of the end of the permanent upper pole scapho-temporal suture more than
      3 months after surgery requiring simple outpatient suture trimming/removal
      without any recurrence of results. Palpable or bridging sutures were present upon
      clinical examination in 10 patients (5%) but did not require revision surgery.
      CONCLUSIONS: Here, we describe a fast, safe and reliable technique for otoplasty
      with no need for extensive dissection, which is applicable to the full range of
      deformity.

PMID- 29472157
TI  - Glioblastoma Presenting with Acute Middle Cerebral Artery Territory Infarct.
AB  - Acute ischemic stroke caused by a malignant mass has been described in the
      literature in few case reports. We describe an unusual case of acute ischemic
      middle cerebral artery distribution infarction secondary to glioblastoma.

PMID- 29472156
TI  - Novel biomarkers in bladder cancer.
AB  - A sea change has occurred in the treatment options available for metastatic
      urothelial bladder cancer with the recent Food and Drug Administration approval
      of 5 immune checkpoint blockade agents for patients who have progressed on
      platinum-based chemotherapy or are not candidates for cisplatin. Additionally,
      comprehensive characterization of the landscape of genomic alterations in this
      disease through The Cancer Genome Atlas and other efforts has detected numerous
      potential targets for small molecule inhibitors. Detailed analysis of the
      urothelial carcinoma transcriptome has allowed for molecular subtyping of the
      disease and the ramifications of these subtypes upon treatment response is an
      active area of investigation. Coupled with these advances is a critical unmet
      need to define predictive biomarkers of response to therapy. Here, we highlight
      select research relevant to the validation and continued discovery of novel
      biomarkers to advance precision oncology in bladder cancer.

PMID- 29472158
TI  - [Dumbbell malignant dorsal schwannoma embolized and operated by single posterior
      approach].
AB  - We report a case of a 41 years old patient complaining of chronic dorsalgia. MRI
      showed a well defined intradural extramedular dumbbell-shaped lesion, associated
      to a left paravertebral tumor at D5-D6 level. The tumor was embolizated prior to
      surgery. Following she underwent a D4-D6 laminotomy, left D5-D6
      costotransversectomy and resection of the intracanal extradural part of the
      lesion with section of the left D5 nerve. Posteriorly, complete resection of the
      extracanal portion of the tumor was performed by a postero-lateral approach. The
      anatomopathologic diagnosis was a malignant schwannoma. After the surgery, the
      patient required adyuvant radiotherapic treatment. Malignant schwannoma is a very
      uncommon tumor which belongs to the malignant peripheral nerve sheath tumors
      (MPNST). It develops from Schwann cells. It is frequently associated with type 1
      neurofibromatosis. MPNST usually present local recurrence and can metastatize.

PMID- 29472159
TI  - Bereavement care interventions and outcome criteria planned by community nurses
      in the Canary Islands.
AB  - : Nursing care in bereavement is complex. Primary health care is the ideal
      setting to support the bereaved, but we do not know much about the care plans
      designed by primary health care nurses in the treatment of grief. OBJECTIVE: To
      identify the outcomes criteria and interventions planned by nurses for mourners
      with and without complications in the Canary Islands. METHOD: Retrospective
      longitudinal study, using the electronic health records of the Canary Islands
      health service of people with a diagnosis of grieving, risk of complicated
      grieving and complicated grieving, in the period 2009-2014. RESULTS: NOC outcomes
      criteria were recorded in 67% of the mourners, and up to 24 different outcomes
      were identified. The main outcomes measures were Grief resolution; Psychosocial
      adjustment, Life change; Coping; Family coping; Family social climate and
      Caregiver emotional health. The remaining outcomes were present in less than 1%
      of the mourners. Although the outcomes criteria proposed by nurses in the
      mourners with and without complications were quite homogeneous, differences in
      interventions were found. In 67% of the cases, NIC interventions were reported.
      Ninety-nine different interventions were identified in the mourners; the most
      frequent were Emotional support; Grief work facilitation; Active listening;
      Coping enhancement and counselling. The remaining identified interventions were
      present in less than 5% of patients. The main interventions in the mourners with
      complications were Grief work facilitation; Coping enhancement; Active listening;
      Counselling and Family integrity promotion. CONCLUSION: Nurses state that there
      are more interventions and outcomes in mourners with complications. Given the few
      methodologically reliable studies that prove their effectiveness, continued
      research in this area is recommended.

PMID- 29472161
TI  - Overview of the management of postural tachycardia syndrome in pregnant patients.
AB  - Postural tachycardia syndrome (POTS) is a chronic condition characterized by
      symptoms of orthostatic intolerance. Pregnancy can cause different physiological
      changes in cardiovascular parameters, that could have greater impact on POTS
      patients. In this review, we discuss the management of POTS in the pregnant and
      obstetric settings.

PMID- 29472160
TI  - Babesia microti thioredoxin 3 is an effective antioxidant and involved in the
      response to antiprotozoal drugs.
AB  - The intra-erythrocytic apicomplexan Babesia microti is the predominant pathogen
      that causes human babesiosis, an infectious disease that occurs worldwide. B.
      microti relies on the antioxidant including thioredoxin system to maintain the
      redox balance during the erythrocytic stage. In the present study, the full
      length B. microti thioredoxin 3 (BmTrx3) gene was cloned, expressed in vitro, and
      its response to antiprotozoal drugs were tested. The full-length BmTrx3 was 663
      bp and contained an intact open reading frame of 567 bp. The encoded polypeptide
      was 188 amino acids and the predicted molecular weight of the protein was 21.7
      kDa. A conserved thioredoxin-like family domain was found in BmTrx3. The
      expression of BmTrx3 was upregulated on both the third and eighth day post
      infection in mice, whereas expression was downregulated during the beginning and
      later stages. Western blot analysis showed that mouse anti-BmTrx3 serum could
      recognize the native BmTrx3 in parasite lysates and that the mouse anti-B.
      microti serum could recognize the recombinant BmTrx3 protein. Immunofluorescence
      microscopy showed that BmTrx3 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 enzyme activity of the purified recombinant BmTrx3
      protein. The anti-malaria drug chloroquine significantly inhibited the expression
      of BmTrx3, however, another anti-malaria drug qunine, and a known anti-babesiosis
      drug clindamycin, induced significantly higher upregulation of BmTrx3 mRNA. The
      results of the present study demonstrate that BmTrx3 is a functional enzyme with
      antioxidant activity and may be involved in the response of B. microti to anti
      parasite drugs.

PMID- 29472162
TI  - "Schizophrenia" and "psychosis" in Italian national newspapers: Do these terms
      convey different messages?

PMID- 29472163
TI  - Validation of an algorithm-based definition of treatment resistance in patients
      with schizophrenia.
AB  - Large-scale pharmacoepidemiological research on treatment resistance relies on
      accurate identification of people with treatment-resistant schizophrenia (TRS)
      based on data that are retrievable from administrative registers. This is usually
      approached by operationalising clinical treatment guidelines by using
      prescription and hospital admission information. We examined the accuracy of an
      algorithm-based definition of TRS based on clozapine prescription and/or meeting
      algorithm-based eligibility criteria for clozapine against a gold standard
      definition using case notes. We additionally validated a definition entirely
      based on clozapine prescription. 139 schizophrenia patients aged 18-65years were
      followed for a mean of 5years after first presentation to psychiatric services in
      South-London, UK. The diagnostic accuracy of the algorithm-based measure against
      the gold standard was measured with sensitivity, specificity, positive predictive
      value (PPV) and negative predictive value (NPV). A total of 45 (32.4%)
      schizophrenia patients met the criteria for the gold standard definition of TRS;
      applying the algorithm-based definition to the same cohort led to 44 (31.7%)
      patients fulfilling criteria for TRS with sensitivity, specificity, PPV and NPV
      of 62.2%, 83.0%, 63.6% and 82.1%, respectively. The definition based on lifetime
      clozapine prescription had sensitivity, specificity, PPV and NPV of 40.0%, 94.7%,
      78.3% and 76.7%, respectively. Although a perfect definition of TRS cannot be
      derived from available prescription and hospital registers, these results
      indicate that researchers can confidently use registries to identify individuals
      with TRS for research and clinical practices.

PMID- 29472165
TI  - Aberrant cerebellar-default-mode functional connectivity underlying auditory
      verbal hallucinations in schizophrenia revealed by multi-voxel pattern analysis
      of resting-state functional connectivity MRI data.

PMID- 29472164
TI  - Associations of independent living and labor force participation with impairment
      indicators in schizophrenia and bipolar disorder at 20-year follow-up.
AB  - BACKGROUND: Since the Iowa 500 study, residential and occupational status have
      been frequently used as indicators of everyday achievements in research on
      schizophrenia and bipolar disorder. The relationships of residential and
      occupational status with impairment in multiple domains including physical health
      indicators across these two diagnoses, however, have rarely been studied. We
      examined these relationships at the 20-year follow-up assessment of a first
      admission sample. METHODS: We included 146 participants with schizophrenia and 87
      with bipolar disorder with psychosis who participated in the 20-year follow-up of
      the Suffolk County Mental Health Project. In addition to interviewer-based
      ratings of employment and residential independence, we examined self-reported
      impairment derived from the WHODAS, standard measures of current psychopathology,
      indicators of obesity, as well as performance-based measures of physical and
      cognitive functioning. RESULTS: Participants with bipolar disorder were more
      likely to live independently and be gainfully employed; they also performed
      significantly better on each indicator of impairment apart from balance ability.
      In both groups, unemployment, but not residential independence, was associated
      with greater self-reported disability on the WHODAS. Residential independence,
      gainful employment, and subjective disability were also associated with better
      physical functioning. Across the two groups, psychiatric symptoms and physical
      functioning were the major determinants of subjective disability. DISCUSSION:
      People with psychotic bipolar disorder were more likely to be gainfully employed
      and living independently than participants with schizophrenia but as a group,
      much less frequently than population standards. Interventions aimed at physical
      fitness may have the potential to improve both objective functioning and
      perceived disability.

PMID- 29472166
TI  - Conceptual disorganization and dissociative symptoms in women with first episode
      psychosis.

PMID- 29472167
TI  - Preliminary evidence for neural responsiveness to infants in mothers with
      schizophrenia and the implications for healthy parenting.
AB  - Schizophrenia is a severe mental illness that may significantly affect maternal
      sensitive behaviour. Neural correlates of maternal behaviour represent a
      potentially valuable means of differentiating objectively between healthy mothers
      expressing variations in maternal sensitivity. As mothers with schizophrenia
      (MWS) show deficits in behavioural responses to infants compared to healthy
      mothers, we explored whether maternal brain responses to infant stimuli would be
      significantly reduced in MWS. We also examined whether differences in maternal
      behaviour between healthy and ill mothers (during play interactions with own
      infant) were associated with differences in brain activation to infant stimuli.
      We found no evidence of differential 'maternal brain' responses or 'maternal
      behavioural' responses in 11 new MWS compared to 20 healthy new mums; neither
      were neural responses to infants linked to behavioural or cognitive aspects of
      the mother's relationship with her infant in MWS. These preliminary findings
      suggest maternal sensitivity differences between MWS and healthy mothers,
      suggested in previous studies, may be reversible in stable treated MWS.

PMID- 29472168
TI  - Stability of Locking Plate and Compression Screws for Lapidus Arthrodesis: A
      Biomechanical Comparison of Plate Position.
AB  - Lapidus (first tarsometatarsal joint) arthrodesis is an established and widely
      used procedure for the management of moderate to severe hallux valgus, especially
      in cases involving hypermobility of the first tarsometatarsal joint. Multiple
      fixation methods are available, and several previous investigations have studied
      the relative strengths of these methods, including dorsomedial and plantar
      plating comparisons. However, these studies compared plates of varying designs
      and mechanical properties and used varying modes of compression and
      interfragmentary screw techniques. The present study mechanically investigated
      the resulting motion, stiffness, and strength of identical locking plate
      constructs fixed at various anatomic positions around the first tarsometatarsal
      joint. In a bench-top study, fourth-generation composite bones were divided into
      3 fixation groups, each having identical interfragmentary screw applications, and
      randomized to 1 of 3 plate positions: dorsal, medial, or plantar. The plates
      applied in each case were identical locking plates, precontoured to fit the
      anatomy. Each construct was experimentally tested using a cantilever bending
      approach. The outcomes obtained were stiffness, yield force, displacement at
      yield, ultimate force, and displacement at ultimate force. The plantar plate
      position showed superior initial stiffness and force to ultimate failure. The
      plantar and medial plate positions exhibited superior force to yield. The medial
      plate position was superior regarding displacement tolerated before the yield
      point and catastrophic failure. The dorsal plate position was not superior for
      any outcome measured. Plantar and medial plating each offered biomechanical
      benefits. Clinical studies using similarly matched constructs are required to
      show whether these findings translate into improved clinical outcomes.

PMID- 29472169
TI  - Malignant Hidradenocarcinoma in the Lower Extremity: A Case Report of a Rare
      Tumor.
AB  - Malignant hidradenocarcinomas are rare soft tissue tumors of sweat gland origin.
      We present the case of a soft tissue, fungating tumor of 15 years' duration of
      the medial ankle in an 85-year-old male that exhibited malignant features
      clinically and radiographically. Subsequent punch biopsy revealed a diagnosis of
      malignant hidradenocarcinoma. Given the risk of recurrence and the poor radiation
      and chemotherapy options, the patient initially decided to leave the lesion
      untreated. However, he soon developed lower extremity cellulitis from the exposed
      lesion and decided to have the tumor excised, eliminating the source of the
      infection. In the present case study, we discuss the etiology, clinical and
      radiographic characteristics, and treatment options for this rare lesion. At the
      18-month follow-up visit, he had had no recurrence of the lesion.

PMID- 29472170
TI  - Surgical Treatment of Neglected Bilateral Hemophilic Equinus Contracture With
      External Fixation: A Case Report.
AB  - Hemophilia is a disorder of blood coagulation with X-linked recessive
      inheritance. It is characterized by uncontrollable hemorrhage, and 80% of these
      occur intraarticularly. With recurrent hemarthrosis, recurrent synovitis occurs,
      which eventually leads to the formation of articular contractures. The key to the
      prevention of hemophilic joint complications is successful prevention of bleeding
      and management of the initial hemarthrosis. However, after the development of a
      rigid contracture, surgical correction remains the only method to correct the
      deformity. Achilles tendon lengthening, synovectomy, anterior osteophyte
      resection, corrective osteotomies, external fixators, or arthrodesis should be
      considered as surgical options. In the present report, we describe our experience
      using hybrid-type external fixators to manage bilateral neglected rigid equinus
      contractures in a hemophilic patient, with 78 months of follow-up data.

PMID- 29472171
TI  - Treatment of uveitis and ankylosing spondylitis refractory to three tumor
      necrosis factor alpha inhibitors drugs with golimumab.

PMID- 29472172
TI  - Shrinking lung syndrome and pleural effusion as an initial manifestation of
      primary Sjogren's syndrome.

PMID- 29472173
TI  - Co-Designing a Collaborative Chronic Care Network (C3N) for Inflammatory Bowel
      Disease: Development of Methods.
AB  - BACKGROUND: Our health care system fails to deliver necessary results, and
      incremental system improvements will not deliver needed change. Learning health
      systems (LHSs) are seen as a means to accelerate outcomes, improve care delivery,
      and further clinical research; yet, few such systems exist. We describe the
      process of codesigning, with all relevant stakeholders, an approach for creating
      a collaborative chronic care network (C3N), a peer-produced networked LHS.
      OBJECTIVE: The objective of this study was to report the methods used, with a
      diverse group of stakeholders, to translate the idea of a C3N to a set of
      actionable next steps. METHODS: The setting was ImproveCareNow, an improvement
      network for pediatric inflammatory bowel disease. In collaboration with patients
      and families, clinicians, researchers, social scientists, technologists, and
      designers, C3N leaders used a modified idealized design process to develop a
      design for a C3N. RESULTS: Over 100 people participated in the design process
      that resulted in (1) an overall concept design for the ImproveCareNow C3N, (2) a
      logic model for bringing about this system, and (3) 13 potential innovations
      likely to increase awareness and agency, make it easier to collect and share
      information, and to enhance collaboration that could be tested collectively to
      bring about the C3N. CONCLUSIONS: We demonstrate methods that resulted in a
      design that has the potential to transform the chronic care system into an LHS.

PMID- 29472175
TI  - Impact of a Student-Driven, Virtual Patient Application on Objective Structured
      Clinical Examination Performance: Observational Study.
AB  - BACKGROUND: Peer-assisted learning (PAL) refers to a learning activity whereby
      students of similar academic level teach and learn from one another. Groupe de
      perfectionnement des habiletes cliniques (Clinical Skills Improvement Group), a
      student organization at Universite Laval, Canada, propelled PAL into the digital
      era by creating a collaborative virtual patient platform. Medical interviews can
      be completed in pairs (a student-patient and a student-doctor) through an
      interactive Web-based application, which generates a score (weighted for key
      questions) and automated feedback. OBJECTIVES: The aim of the study was to
      measure the pedagogical impact of the application on the score at medical
      interview stations at the summative preclerkship Objective Structured Clinical
      Examination (OSCE). METHODS: We measured the use of the application (cases
      completed, mean score) in the 2 months preceding the OSCE. We also accessed the
      results of medical interview stations at the preclerkship summative OSCE. We
      analyzed whether using the application was associated with higher scores and/or
      better passing grades (>=60%) at the OSCE. Finally, we produced an online form
      where students could comment on their appreciation of the application. RESULTS:
      Of the 206 students completing the preclerkship summative OSCE, 170 (82.5%) were
      registered users on the application, completing a total of 3133 cases (18 by
      active user in average, 7 minutes by case in average). The appreciation
      questionnaire was answered online by 45 students who mentioned appreciating the
      intuitive, easy-to-use, and interactive design, the diversity of cases, and the
      automated feedback. Using the application was associated with reduced reported
      stress, improved scores (P=.04), and improved passing rates (P=.11) at the
      preclerkship summative OSCE. CONCLUSIONS: This study suggests that PAL can go far
      beyond small-group teaching, showing students' potential to create helpful
      pedagogical tools for their peers.

PMID- 29472176
TI  - Inducing Behavioral Change in Seekers of Pro-Anorexia Content Using Internet
      Advertisements: Randomized Controlled Trial.
AB  - BACKGROUND: The influence of pro-anorexia (pro-ana) websites is debated, with
      studies indicating both negative and positive effects, as well as significant
      variation in the effects of different websites for those suffering from eating
      disorders (EDs) and the general population. Online advertising, known to induce
      behavioral change both online and in the physical world, has not been used so far
      to modify the search behavior of people seeking pro-ana content. OBJECTIVE: The
      objective of this randomized controlled trial (RCT) was to examine if online
      advertisements (ads) can change online search behaviors of users who are looking
      for online pro-ana content. METHODS: Using the Bing Ads system, we conducted an
      RCT to randomly expose the searchers for pro-ana content to 10 different ads
      referring people to one of the three websites: the National Eating Disorders
      Association, the National Institutes of Mental Health, and MyProAna. MyProAna is
      a pro-ana website that was found in a previous study to be associated with less
      pathological online behaviors than other pro-ana websites. We followed
      participants exposed and unexposed to the ads to explore their past and future
      online searches. The ads were shown 25,554 times and clicked on 217 times.
      RESULTS: Exposure to the ads was associated with a decrease in searches for pro
      ana and self-harm content. Reductions were greatest among those referred to
      MyProAna (reduction of 34.0% [73/215] and 37.2% [80/215] for pro-ana and self
      harm, respectively) compared with users who were referred elsewhere (reduction of
      15.47% [410/2650] and 3.21% [85/2650], respectively), and with users who were not
      shown the ads, who increased their behaviors (increase of 57.12% [6462/11,314]
      and 4.07% [461/11,314], respectively). In addition, those referred to MyProAna
      increased their search for treatment, as did control users, who did so to a
      lesser extent. However, users referred elsewhere decreased their searches for
      this content. CONCLUSIONS: We found that referring users interested in ED-related
      content to specific pro-ana communities might lessen their maladaptive online
      search behavior. This suggests that those who are preoccupied with EDs can be
      redirected to less pathological online searches through appropriate pathways.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT03439553;
      https://clinicaltrials.gov/show/NCT03439553 (Archived by WebCite at
      http://www.webcitation.org/6xNYnxYlw).

PMID- 29472174
TI  - Peer-Based Social Media Features in Behavior Change Interventions: Systematic
      Review.
AB  - BACKGROUND: Incorporating social media features into digital behavior change
      interventions (DBCIs) has the potential to contribute positively to their
      success. However, the lack of clear design principles to describe and guide the
      use of these features in behavioral interventions limits cross-study comparisons
      of their uses and effects. OBJECTIVE: The aim of this study was to provide a
      systematic review of DBCIs targeting modifiable behavioral risk factors that have
      included social media features as part of their intervention infrastructure. A
      taxonomy of social media features is presented to inform the development,
      description, and evaluation of behavioral interventions. METHODS: Search terms
      were used in 8 databases to identify DBCIs that incorporated social media
      features and targeted tobacco smoking, diet and nutrition, physical activities,
      or alcohol consumption. The screening and review process was performed by 2
      independent researchers. RESULTS: A total of 5264 articles were screened, and 143
      articles describing a total of 134 studies were retained for full review. The
      majority of studies (70%) reported positive outcomes, followed by 28% finding no
      effects with regard to their respective objectives and hypothesis, and 2% of the
      studies found that their interventions had negative outcomes. Few studies
      reported on the association between the inclusion of social media features and
      intervention effect. A taxonomy of social media features used in behavioral
      interventions has been presented with 36 social media features organized under 7
      high-level categories. The taxonomy has been used to guide the analysis of this
      review. CONCLUSIONS: Although social media features are commonly included in
      DBCIs, there is an acute lack of information with respect to their effect on
      outcomes and a lack of clear guidance to inform the selection process based on
      the features' suitability for the different behaviors. The proposed taxonomy
      along with the set of recommendations included in this review will support future
      research aimed at isolating and reporting the effects of social media features on
      DBCIs, cross-study comparisons, and evaluations.

PMID- 29472177
TI  - Implementation of the Enhanced Moderated Online Social Therapy (MOST+) Model
      Within a National Youth E-Mental Health Service (eheadspace): Protocol for a
      Single Group Pilot Study for Help-Seeking Young People.
AB  - BACKGROUND: There is a substantial need for youth electronic mental health (e
      mental health) services. In addressing this need, our team has developed a novel
      moderated online social therapy intervention called enhanced moderated online
      social therapy (MOST+). MOST+ integrates real-time, clinician-delivered Web chat
      counseling, interactive user-directed online therapy, expert and peer moderation,
      and private and secure peer-to-peer social networking. MOST+ has been designed to
      give young people immediate, 24-hour access to anonymous, evidence-based, and
      short-term mental health care. OBJECTIVE: The primary aims of this pilot study
      were to determine the feasibility, acceptability, and safety of the intervention.
      Secondary aims were to assess prepost changes in key psychosocial outcomes and
      collect qualitative data for future intervention refinement. METHODS: MOST+ will
      be embedded within eheadspace, an Australian youth e-mental health service, and
      will be evaluated via an uncontrolled single-group study. Approximately 250 help
      seeking young people (16-25 years) will be progressively recruited to the
      intervention from the eheadspace home page over the first 4 weeks of an 8-week
      intervention period. All participants will have access to evidence-based
      therapeutic content and integrated Web chat counseling. Additional access to
      moderated peer-to-peer social networking will be granted to individuals for whom
      it is deemed safe and appropriate, through a three-tiered screening process.
      Participants will be enrolled in the MOST+ intervention for 1 week, with the
      option to renew their enrollment across the duration of the pilot. Participants
      will complete a survey at enrollment to assess psychological well-being and other
      mental health outcomes. Additional assessment will occur following account
      deactivation (ie, after participant has opted not to renew their enrollment, or
      at trial conclusion) and will include an online survey and telephone interview
      assessing psychological well-being and experience of using MOST+. RESULTS:
      Recruitment for the study commenced in October 2017. We expect to have initial
      results in March 2018, with more detailed qualitative and quantitative analyses
      to follow. CONCLUSIONS: This is the first Australia-wide research trial to pilot
      an online social media platform merging real-time clinical support, expert and
      peer moderation, interactive online therapy, and peer-to-peer social networking.
      The importance of the project stems from the need to develop innovative new
      models for the efficient delivery of responsive evidence-based online support to
      help-seeking young people. If successful, this research stands to complement and
      enhance e-mental health services in Australia.

PMID- 29472178
TI  - Telegerontology as a Novel Approach to Address Health and Safety by Supporting
      Community-Based Rural Dementia Care Triads: Randomized Controlled Trial Protocol.
AB  - BACKGROUND: Telegerontology is an approach using videoconferencing to connect an
      interdisciplinary team in a regional specialty center to patients in rural
      communities, which is becoming increasingly practical for addressing current
      limitations in rural community-based dementia care. OBJECTIVE: Using the remotely
      delivered expertise of the Telegerontology dementia care team, we aim to enhance
      the caregiver/patient/physician triad and thereby provide the necessary support
      for the person with dementia to "age in place." METHODS: This is a cluster
      randomized feasibility trial with four rural regions in the province of
      Newfoundland and Labrador, Canada (2 regions randomly assigned to "intervention"
      and 2 to "control"). The study population includes 22 "dementia triads" that
      consist of a community-dwelling older Canadian with moderate to late dementia,
      their family caregivers, and their Primary Care Physician (PCP). Over the 6-month
      active study period, all participants will be provided an iPad. The intervention
      is intended as an adjunct to existing PCP care, consisting of weekly Skype-based
      videoconferencing calls with the Telegerontology physician, and other team
      members as needed (occupational therapist, physical therapist etc). Control
      participants receive usual community-based dementia care with their PCP. A
      baseline (pre-) assessment will be performed during a home visit with the study
      team. Post intervention, 6- and 12-month follow-up assessments will be collected
      remotely using specialized dementia monitoring applications and Skype calls.
      Primary outcomes include admission to long-term care, falls, emergency room
      visits, hospital stays, and caregiver burden. RESULTS: Results will be available
      in March of 2018. CONCLUSIONS: Results from this study will demonstrate a novel
      approach to dementia care that has the potential to impact both rural PCPs,
      family caregivers, and people with dementia, as well as provide evidence for the
      utility of Telegerontology in models of eHealth-based care.

PMID- 29472179
TI  - Representation of Time-Relevant Common Data Elements in the Cancer Data Standards
      Repository: Statistical Evaluation of an Ontological Approach.
AB  - BACKGROUND: Today, there is an increasing need to centralize and standardize
      electronic health data within clinical research as the volume of data continues
      to balloon. Domain-specific common data elements (CDEs) are emerging as a
      standard approach to clinical research data capturing and reporting. Recent
      efforts to standardize clinical study CDEs have been of great benefit in
      facilitating data integration and data sharing. The importance of the temporal
      dimension of clinical research studies has been well recognized; however, very
      few studies have focused on the formal representation of temporal constraints and
      temporal relationships within clinical research data in the biomedical research
      community. In particular, temporal information can be extremely powerful to
      enable high-quality cancer research. OBJECTIVE: The objective of the study was to
      develop and evaluate an ontological approach to represent the temporal aspects of
      cancer study CDEs. METHODS: We used CDEs recorded in the National Cancer
      Institute (NCI) Cancer Data Standards Repository (caDSR) and created a CDE parser
      to extract time-relevant CDEs from the caDSR. Using the Web Ontology Language
      (OWL)-based Time Event Ontology (TEO), we manually derived representative
      patterns to semantically model the temporal components of the CDEs using an
      observing set of randomly selected time-related CDEs (n=600) to create a set of
      TEO ontological representation patterns. In evaluating TEO's ability to represent
      the temporal components of the CDEs, this set of representation patterns was
      tested against two test sets of randomly selected time-related CDEs (n=425).
      RESULTS: It was found that 94.2% (801/850) of the CDEs in the test sets could be
      represented by the TEO representation patterns. CONCLUSIONS: In conclusion, TEO
      is a good ontological model for representing the temporal components of the CDEs
      recorded in caDSR. Our representative model can harness the Semantic Web
      reasoning and inferencing functionalities and present a means for temporal CDEs
      to be machine-readable, streamlining meaningful searches.

PMID- 29472180
TI  - Deep vein thrombosis.

PMID- 29472181
TI  - Improving animal research: PREPARE before you ARRIVE.

PMID- 29472182
TI  - Doctors developing apps to try to modernise the NHS.

PMID- 29472183
TI  - NHS response to vaginal mesh scandal will be reviewed.

PMID- 29472184
TI  - Hospitals in England see deficits grow as wage bills rise and earning capacity
      falls.

PMID- 29472185
TI  - Atypical chest pain in an older woman.

PMID- 29472186
TI  - Minimum alcohol pricing in Wales would cut deaths and hospital admissions, study
      finds.

PMID- 29472187
TI  - Population attributable fraction.

PMID- 29472189
TI  - Government dismisses call to ringfence public health budgets.

PMID- 29472190
TI  - China's "new" silk road.

PMID- 29472191
TI  - Research sponsors who fail to report results to be named and shamed.

PMID- 29472192
TI  - Studying new antibiotics for multidrug resistant infections: are today's patients
      paying for unproved future benefits?

PMID- 29472193
TI  - Outcomes of neonatal jaundice in Taiwan.
AB  - OBJECTIVE: To investigate the burden of clinically significant neonatal jaundice
      (SNJ) in Taiwan, 2000-2010. STUDY DESIGN: The nationwide, population-based health
      insurance database in Taiwan was used to investigate the incidence, kernicterus
      rate and mortality rates of SNJ cohort born between 2000 and 2010. RESULTS: From
      2000 to 2010, up to 242 546 patients admitted with neonatal jaundice (NJ) were
      identified. The incidence of SNJ was 5.9% in 2000 and increased to 13.7% in 2010
      (P<0.001). The mortality rate significantly decreased from 0.51% in 2000 to 0.26%
      in 2010 (P<0.001) and the average incidence of kernicterus was 0.86 per 100 000
      live births, indicating dramatically decreased rates compared with earlier rates
      in Taiwan. CONCLUSIONS: In spite of the increased incidence rates, the rates of
      mortality and kernicterus in patients with NJ significantly declined in Taiwan.
      The public health prevention programme, clinicians' awareness and effective
      management might contribute to the reduction of these acute severe sequelae.

PMID- 29472194
TI  - Paediatric overdiagnosis modelled by coronary abnormality trends in Kawasaki
      disease.
AB  - OBJECTIVE: Compare trends in coronary artery (CA) abnormality diagnoses to trends
      in adverse cardiac outcomes among American children with Kawasaki disease (KD) to
      assess the fit of detection of CA abnormalities to an established model of
      overdiagnosis. DESIGN: Multicenter retrospective cohort. SETTING: 48 US
      children's hospitals in the Paediatric Health Information System database.
      PARTICIPANTS: Children <18 years receiving care for KD between 2000 and 2014.
      MAIN OUTCOME MEASURES: The main outcomes were rates of CA abnormality diagnoses
      and adverse cardiac outcomes, measured during a child's incident KD visit and
      longitudinally at all subsequent visits to the same hospital, through December
      2016. CA abnormalities were considered severe if long-term anticoagulation other
      than aspirin was prescribed. Trends were tested using mixed effects logistic
      regression, adjusting for patient demographics. RESULTS: Among 17 809 children
      treated for KD, a CA abnormality was diagnosed in 1435 children (8%), including
      1117 considered non-severe and 318 severe. The rate of non-severe CA abnormality
      diagnoses increased from 45 per 1000 patients with KD in 2000 to 81 per 1000
      patients with KD in 2014, representing an adjusted 2.3-fold increased odds (95%
      CI 1.8 to 3.0) of diagnosis. There was no significant change in diagnoses of
      severe CA abnormalities. Adverse cardiac outcomes were stable over the study
      period at 19 per 1000 patients with KD (P=0.24 for trend). CONCLUSIONS: The
      rising rate of detection of non-severe CA abnormalities accompanied by an
      unchanging rate of adverse cardiac outcomes among American children with KD fits
      an overdiagnosis pattern.

PMID- 29472196
TI  - The mouth and maltreatment: safeguarding issues in child dental health.

PMID- 29472195
TI  - Acid suppressants for managing gastro-oesophageal reflux and gastro-oesophageal
      reflux disease in infants: a national survey.
AB  - OBJECTIVES: To evaluate the diagnosis and management of reflux and gastro
      oesophageal reflux disease (GORD) in infants aged <1 year presenting to general
      practitioners (GPs). DESIGN, SETTING AND PARTICIPANTS: A nationally
      representative, prospective, cross-sectional survey of GP activity in Australia,
      2006-2016 (Bettering the Evaluation And Care of Health Study). Annually, a random
      sample of around 1000 GPs recorded details for 100 consecutive visits with
      consenting, unidentified patients. OUTCOME MEASURES: Diagnoses of reflux and GORD
      and their management including prescribing of acid-suppressant medicines (proton
      pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs)) and
      counselling, advice or education. RESULTS: Of all infants' visits, 512 (2.7%)
      included a diagnosis of reflux (n=413, 2.2%) or GORD (n=99, 0.5%). From 2006 to
      2016, diagnostic rates decreased for reflux and increased for GORD. Prescribing
      of acid suppressants occurred in 43.6% visits for reflux and 48.5% visits for
      GORD, similar to rates of counselling, advice or education (reflux: 38.5%, GORD:
      43.4% of visits). Prescribing of PPIs increased (statistically significant only
      for visits for reflux), while prescribing of H2RAs decreased. CONCLUSIONS:
      Overprescribing of acid suppressants to infants may be occurring. In infants,
      acid-suppressant medicines are no better than placebo and may have significant
      negative side effects; however, guidelines are inconsistent. Clear, concise and
      consistent guidance is needed. GPs and parents need to understand what is normal
      and limitations of medical therapy. We need a greater understanding of the
      influences on GP prescribing practices, of parents' knowledge and attitudes and
      of the pressures on parents of infants with these conditions.

PMID- 29472197
TI  - Multiple paranasal mucoceles in a child.

PMID- 29472198
TI  - Kangaroo mother care for the prevention of neonatal hypothermia: a randomised
      controlled trial in term neonates.
AB  - OBJECTIVE: To test the hypothesis that kangaroo mother care (KMC) initiated
      either at birth or at 1 hour after birth reduces moderate or severe hypothermia
      in term neonates at (A) 1 hour after birth and (B) at discharge when compared
      with standard thermoregulation care. METHODS: Term neonates born at a tertiary
      delivery centre in Zambia were randomised in two phases (phase 1: birth to 1
      hour, phase 2: 1 hour to discharge) to either as much KMC as possible in
      combination with standard thermoregulation care (KMC group) or to standard
      thermoregulation care (control group). The primary outcomes were moderate or
      severe hypothermia (axillary temperature <36.0 degrees C) at (A) 1 hour after
      birth and (B) at discharge. RESULTS: The proportion of neonates with moderate or
      severe hypothermia did not differ between the KMC and control groups at 1 hour
      after birth (25% vs 27%, relative risk (RR)=0.93, 95% CI 0.59 to 1.4, P=0.78) or
      at discharge (7% vs 2%, RR=2.8, 95% CI 0.6 to 13.9, P=0.16). Hypothermia was not
      found among the infants who had KMC for at least 9 hours or 80% of the hospital
      stay. CONCLUSIONS: KMC practised as much as possible in combination with standard
      thermoregulation care initiated either at birth or at 1 hour after birth did not
      reduce moderate or severe hypothermia in term infants compared with standard
      thermoregulation care. The current study also shows that duration of KMC either
      for at least 80% of the time or at least 9 hours during the day of birth was
      effective in preventing hypothermia in term infants. CLINICAL TRIAL REGISTRATION:
      NCT02189759.

PMID- 29472199
TI  - Question 2: Should nasal mask or binasal prongs be used for continuous positive
      airway pressure in preterm infants?

PMID- 29472201
TI  - Hard Data.

PMID- 29472200
TI  - Degenerative cervical myelopathy.

PMID- 29472202
TI  - Making technology-enabled health care work in general practice.

PMID- 29472203
TI  - Information flow to enable integrated health care: integration or
      interoperability.

PMID- 29472204
TI  - C-reactive protein: guiding antibiotic prescribing decisions at the point of
      care.

PMID- 29472205
TI  - New UK General Practice Core Standards for Advanced Serious Illness and End of
      Life Care.

PMID- 29472206
TI  - Population-based, person-centred end-of-life care: time for a rethink.

PMID- 29472207
TI  - General complaint.

PMID- 29472208
TI  - The GP consultant.

PMID- 29472209
TI  - Organ donation in Wales.

PMID- 29472210
TI  - A squash and a squeeze.

PMID- 29472211
TI  - Requirement for retinal screening in patients taking hydroxychloroquine and
      chloroquine.

PMID- 29472212
TI  - Viewpoint: Professional powerlessness: reflections from a WhatsApp group.

PMID- 29472213
TI  - Something's awry (again) in the debate on patient data sharing.

PMID- 29472214
TI  - Organ donation among ethnic minorities: how UK primary care can help promote it.

PMID- 29472215
TI  - Viewpoint: The Practice Visit - An Obituary.

PMID- 29472216
TI  - Yonder: PTSD, piles, Pharma visits, and parkrun.

PMID- 29472217
TI  - What's in a name? A brief foray into the world of medical linguistics.

PMID- 29472218
TI  - Bad Medicine: Private medicine practice.

PMID- 29472219
TI  - Exhibition: Charles I - King and Collector: All The King's Pictures.

PMID- 29472220
TI  - Books: Is Your Job Making You Ill? How to Survive and Thrive When it Happens to
      You: Some Guidance for Patients and GPs in Tough Times.

PMID- 29472221
TI  - Books: This is Going to Hurt: Secret Diaries of a Junior Doctor: Only When I
      Laugh.

PMID- 29472222
TI  - Books: Mind and Cosmos: Why the Materialist Neo-Darwinian Conception of Nature is
      Almost Certainly False: Can Sentience be Explained by Substance?

PMID- 29472223
TI  - Can everyone stop using the 'F' word?

PMID- 29472224
TI  - Artificial intelligence in medicine: current trends and future possibilities.

PMID- 29472225
TI  - Preventing gatekeeping delays in the diagnosis of rare diseases.

PMID- 29472226
TI  - Finding and using routine clinical datasets for observational research and
      quality improvement.

PMID- 29472227
TI  - Cognitive tests to help diagnose dementia in symptomatic people in primary care
      and the community.

PMID- 29472228
TI  - Secondary prevention following myocardial infarction: a clinical update.

PMID- 29472229
TI  - Management of exertional heat stroke: a practical update for primary care
      physicians.

PMID- 29472230
TI  - Platelets Drive Thrombus Propagation in a Hematocrit and Glycoprotein VI
      Dependent Manner in an In Vitro Venous Thrombosis Model.
AB  - OBJECTIVE: The objective of this study was to measure the role of platelets and
      red blood cells on thrombus propagation in an in vitro model of venous valvular
      stasis. APPROACH AND RESULTS: A microfluidic model with dimensional similarity to
      human venous valves consists of a sinus distal to a sudden expansion, where for
      sufficiently high Reynolds numbers, 2 countercurrent vortices arise because of
      flow separation. The primary vortex is defined by the points of flow separation
      and reattachment. A secondary vortex forms in the deepest recess of the valve
      pocket characterized by low shear rates. An initial fibrin gel formed within the
      secondary vortex of a tissue factor-coated valve sinus. Platelets accumulated at
      the interface of the fibrin gel and the primary vortex. Red blood cells at
      physiological hematocrits were necessary to provide an adequate flux of platelets
      to support thrombus growth out of the valve sinus. A subpopulation of platelets
      that adhered to fibrin expose phosphatidylserine. Platelet-dependent thrombus
      growth was attenuated by inhibition of glycoprotein VI with a blocking Fab
      fragment or D-dimer. CONCLUSIONS: A 3-step process regulated by hemodynamics was
      necessary for robust thrombus propagation: First, immobilized tissue factor
      initiates coagulation and fibrin deposition within a low flow niche defined by a
      secondary vortex in the pocket of a model venous valve. Second, a primary vortex
      delivers platelets to the fibrin interface in a red blood cell-dependent manner.
      Third, platelets adhere to fibrin, activate through glycoprotein VI, express
      phosphatidylserine, and subsequently promote thrombus growth beyond the valve
      sinus and into the bulk flow.

PMID- 29472231
TI  - Carotid Artery Remodeling Is Segment Specific: An In Vivo Study by Vessel Wall
      Magnetic Resonance Imaging.
AB  - OBJECTIVE: Early atherosclerosis is often undetected due in part to compensatory
      enlargement of the outer wall, termed positive remodeling. Variations in
      hemodynamic conditions and clinical factors influence the patterns of remodeling.
      The carotid artery provides an opportunity to examine these variations because of
      the unique geometry of the carotid bulb. This study aimed to determine
      differences in remodeling of the common, internal, and bifurcation segments of
      the carotid using magnetic resonance imaging. APPROACH AND RESULTS: Carotid
      arteries of 525 subjects without history of cardiovascular disease were imaged by
      magnetic resonance imaging. The carotid artery was divided into 3 segments:
      common carotid artery; bifurcation; and internal carotid artery. Remodeling
      patterns were characterized using linear regression analysis of lumen and total
      vessel areas (dependent variables) compared with maximum wall thickness
      (independent variable) for each segment, adjusted for age, sex, and height. The
      common carotid artery demonstrated a pattern consistent with positive remodeling,
      whereas the bifurcation demonstrated negative remodeling. The internal carotid
      artery demonstrated a mixed pattern of outer wall expansion and lumen
      constriction. Females and subjects with diabetes mellitus showed more positive
      remodeling, hypertension was associated with attenuated positive remodeling, and
      those with hypercholesterolemia showed more negative remodeling. CONCLUSIONS: In
      this cohort of 55- to 80-year-old individuals without history of cardiovascular
      disease, the pattern of early carotid artery remodeling was segment specific and
      appeared to be associated with sex and clinical characteristics. These findings
      provide the groundwork for longitudinal studies to define local and systemic
      factors such as hemodynamic and clinical conditions on carotid artery remodeling.

PMID- 29472234
TI  - Hypoxia Triggers SENP1 (Sentrin-Specific Protease 1) Modulation of KLF15 (Kruppel
      Like Factor 15) and Transcriptional Regulation of Arg2 (Arginase 2) in Pulmonary
      Endothelium.
AB  - OBJECTIVE: KLF15 (Kruppel-like factor 15) has recently been shown to suppress
      activation of proinflammatory processes that contribute to atherogenesis in
      vascular smooth muscle, however, the role of KLF15 in vascular endothelial
      function is unknown. Arginase mediates inflammatory vasculopathy and vascular
      injury in pulmonary hypertension. Here, we tested the hypothesis that KLF15 is a
      critical regulator of hypoxia-induced Arg2 (arginase 2) transcription in human
      pulmonary microvascular endothelial cells (HPMEC). APPROACH AND RESULTS:
      Quiescent HPMEC express ample amounts of full-length KLF15. HPMECs exposed to 24
      hours of hypoxia exhibited a marked decrease in KLF15 protein levels and a
      reciprocal increase in Arg2 protein and mRNA. Chromatin immunoprecipitation
      indicated direct binding of KLF15 to the Arg2 promoter, which was relieved with
      HPMEC exposure to hypoxia. Furthermore, overexpression of KLF15 in HPMEC reversed
      hypoxia-induced augmentation of Arg2 abundance and arginase activity and rescued
      nitric oxide (NO) production. Ectopic KLF15 also reversed hypoxia-induced
      endothelium-mediated vasodilatation in isolated rat pulmonary artery rings.
      Mechanisms by which hypoxia regulates KLF15 abundance, stability, and
      compartmentalization to the nucleus in HPMEC were then investigated. Hypoxia
      triggered deSUMOylation of KLF15 by SENP1 (sentrin-specific protease 1), and
      translocation of KLF15 from nucleus to cytoplasm. CONCLUSIONS: KLF15 is a
      critical regulator of pulmonary endothelial homeostasis via repression of
      endothelial Arg2 expression. KLF15 abundance and nuclear compartmentalization are
      regulated by SUMOylation/deSUMOylation-a hypoxia-sensitive process that is
      controlled by SENP1. Strategies including overexpression of KLF15 or inhibition
      of SENP1 may represent novel therapeutic targets for pulmonary hypertension.

PMID- 29472233
TI  - Novel Role of IL (Interleukin)-1beta in Neutrophil Extracellular Trap Formation
      and Abdominal Aortic Aneurysms.
AB  - OBJECTIVE: Neutrophils promote experimental abdominal aortic aneurysm (AAA)
      formation via a mechanism that is independent from MMPs (matrix
      metalloproteinases). Recently, we reported a dominant role of IL (interleukin)
      1beta in the formation of murine experimental AAAs. Here, the hypothesis that IL
      1beta-induced neutrophil extracellular trap formation (NETosis) promotes AAA was
      tested. APPROACH AND RESULTS: NETs were identified through colocalized staining
      of neutrophil, Cit-H3 (citrullinated histone H3), and DNA, using
      immunohistochemistry. NETs were detected in human AAAs and were colocalized with
      IL-1beta. In vitro, IL-1RA attenuated IL-1beta-induced NETosis in human
      neutrophils. Mechanistically, IL-1beta treatment of isolated neutrophils induced
      nuclear localization of ceramide synthase 6 and synthesis of C16-ceramide, which
      was inhibited by IL-1RA or fumonisin B1, an inhibitor of ceramide synthesis.
      Furthermore, IL-1RA or fumonisin B1 attenuated IL1-beta-induced NETosis. In an
      experimental model of murine AAA, NETs were detected at a very early stage-day 3
      of aneurysm induction. IL-1beta-knockout mice demonstrated significantly lower
      infiltration of neutrophils to aorta and were protected from AAA. Adoptive
      transfer of wild-type neutrophils promoted AAA formation in IL-1beta-knockout
      mice. Moreover, treatment of wild-type mice with Cl-amidine, an inhibitor
      NETosis, significantly attenuated AAA formation, whereas, treatment with
      deoxyribonuclease, a DNA digesting enzyme, had no effect on AAA formation.
      CONCLUSIONS: Altogether, the results suggest a dominant role of IL-1beta-induced
      NETosis in AAA formation.

PMID- 29472235
TI  - Aid agencies call for access to besieged Eastern Ghouta.

PMID- 29472232
TI  - Genome-Wide Association and Functional Studies Identify SCML4 and THSD7A as Novel
      Susceptibility Genes for Coronary Artery Disease.
AB  - OBJECTIVE: The genetic contribution to coronary artery disease (CAD) remains
      largely unclear. We combined genetic screening with functional characterizations
      to identify novel loci and candidate genes for CAD. APPROACH AND RESULTS: We
      performed genome-wide screening followed by multicenter validation in 8 cohorts
      consisting of 21 828 participants of Han ethnicity and identified 3 novel
      intragenic SNPs (single nucleotide polymorphisms), rs9486729 (SCML4 [Scm polycomb
      group protein-like 4]; odds ratio, 1.25; 95% CI, 1.17-1.34; P=3.51*10-11),
      rs17165136 (THSD7A [thrombospondin type 1 domain-containing 7A]; odds ratio 1.28;
      95% CI, 1.21-1.35; P<1.00*10-25), and rs852787 (DAB1 [disabled-1]; odds ratio,
      1.29; 95% CI, 1.21-1.38; P=2.02*10-14), associated with CAD with genome-wide
      significance. The risk allele of rs9486729 and protective allele of rs17165136
      were associated with the decreased expression of their host genes, SCML4 and
      THSD7A, respectively, whereas rs852787 did not have transcriptional effects on
      any gene. Knockdown of SCML4 activated endothelial cells by increasing the
      expression of IL-6, E-selectin, and ICAM and weakened their antiapoptotic
      activity, whereas the knockdown of THSD7A had little effect on these endothelial
      cell functions but attenuated monocyte adhesion via decreasing the expression of
      ICAM, L-selectin, and ITGB2. We further showed that inhibiting the expression of
      SCML4 exacerbated endothelial dysfunction and vascular remodeling in a rat model
      with partial carotid ligation. CONCLUSIONS: We identify 3 novel loci associated
      with CAD and show that 2 genes, SCML4 and THSD7A, make functional contributions
      to atherosclerosis. How rs852787 and its host gene DAB1 are linked to CAD needs
      further studies.

PMID- 29472236
TI  - Assessment of choroidal blood flow using laser speckle flowgraphy.
AB  - BACKGROUND/AIMS: There is considerable interest in novel techniques to quantify
      choroidal blood flow (CBF) in humans. In the present study, we investigated a
      novel technique to measure CBF based on laser speckle flowgraphy (LSFG) in
      healthy subjects. METHODS: This study included 31 eyes of 31 healthy, non-smoking
      subjects aged between 19 and 74 years. A commercial LSFG instrument was used to
      measure choroidal vessel diameter (CVD) and relative flow volume (RFV) in
      choroidal vessels that were identified on fundus photos, an approach that was
      used previously only for retinal vessels. The reproducibility and the effect of
      isometric exercise on these parameters were investigated. The latter was compared
      with measurement of subfoveal CBF using laser Doppler flowmetry (LDF). RESULTS:
      Intraclass correlation coefficients for CVD and RFV were higher than 0.8
      indicating excellent reproducibility. During isometric exercise, we observed an
      increase in ocular perfusion pressure of approximately 60% (P<0.001). The
      increase in RFV and CBF was lower, but also highly significant versus baseline
      (at minute 6 of isometric exercise: RFV 10.5%+/-4.2%, CBF 8.3%+/-3.6%; P<0.001
      each) indicating choroidal autoregulation. CONCLUSION: LSFG may be a novel
      approach to study blood flow in choroidal vessels. Data are reproducible and show
      good agreement with LDF data. TRIAL REGISTRATION NUMBER: NCT02102880, Results.

PMID- 29472238
TI  - Divided we fall: the commodification of primary medical care.

PMID- 29472239
TI  - CAR T-cell Therapies Produce Durable Remissions.
AB  - Two studies reported durable long-term remissions in patients with acute
      lymphoblastic leukemia treated with CAR T-cell therapies. One study focused on
      children and young adults treated with tisagenlecleucel; the other focused on
      adults who received infusions of 19-28z CAR T cells.

PMID- 29472240
TI  - Clinical Factors Predict Atezolizumab Response.
AB  - Researchers have presented a new model that uses six readily available clinical
      factors to predict whether a patient with advanced bladder cancer who has already
      received platinum chemotherapy will respond to treatment with the PD-L1 inhibitor
      atezolizumab. The results may help patients and their doctors decide how to
      proceed with treatment.

PMID- 29472242
TI  - What police officers want public health professionals to know.

PMID- 29472241
TI  - Adrenal activity and metabolic risk during randomized escitalopram or placebo
      treatment in PCOS.
AB  - BACKGROUND/AIMS: Polycystic ovary syndrome (PCOS) is associated with insulin
      resistance, adrenal hyperactivity and decreased mental health. We aimed to
      investigate the changes in adrenal activity, metabolic status and mental health
      in PCOS during treatment with escitalopram or placebo. METHODS: Forty-two
      overweight premenopausal women with PCOS and no clinical depression were
      randomized to 12-week SSRI (20 mg escitalopram/day, n = 21) or placebo (n = 21).
      Patients underwent clinical examination, fasting blood samples,
      adrenocorticotroph hormone (ACTH) test, 3-h oral glucose tolerance test (OGTT)
      and filled in questionnaires regarding mental health and health-related quality
      of life (HRQoL): WHO Well-Being Index (WHO-5), Major Depression Inventory (MDI),
      Short Form 36 (SF-36) and PCOS questionnaire. RESULTS: Included women were aged
      31 (6) years (mean (s.d.)) and had body mass index (BMI) 35.8 (6.5) kg/m2 and
      waist 102 (12) cm. Escitalopram was associated with increased waist (median
      (quartiles) change 1 (0; 3) cm), P = 0.005 vs change during placebo and increased
      cortisol levels (cortisol 0, cortisol 60, peak cortisol and area under the curve
      for cortisol during ACTH test), all P  < 0.05 vs changes during placebo.
      Escitalopram had no significant effect on measures of insulin sensitivity,
      insulin secretion, fasting lipids, mental health or HRQoL. CONCLUSION: Waist
      circumference and cortisol levels increased during treatment with escitalopram in
      women with PCOS and no clinical depression, whereas metabolic risk markers,
      mental health and HRQol were unchanged.

PMID- 29472243
TI  - If the papers don't come to the journal....

PMID- 29472244
TI  - Age and Other Factors Affecting the Outcome of AABR Screening in Neonates.
AB  - BACKGROUND: Although the utility of universal newborn hearing screening is
      undisputed, testing protocols vary. In particular, the impact of the infant's age
      at the time of automated auditory brainstem response (AABR) screening has not
      been well studied. METHODS: We conducted a retrospective review of newborn
      hearing screening data in 6817 low-risk, term and late-preterm newborns at our
      large, urban, academic medical center for a 1-year period to analyze the impact
      of age and other factors on the screening failure rate and referral for
      diagnostic testing. RESULTS: AABR screening failure rates decreased with
      postnatal age over the first 48 hours; 13.3% failed at <24 hours versus 3.8% at
      >=48 hours (P < .0001). Infants who were initially tested at >=36 hours failed
      repeat testing more often than those who were tested at <36 hours (11.5% vs
      18.9%; P = .03). Other factors that were associated with failure included being a
      boy and of a race other than white. Sensorineural hearing loss (SNHL) was
      diagnosed in 18.6% of infants who failed their final screening at >=48 hours
      compared with 2.8% of those whose final screening occurred earlier (P = .03).
      SNHL was more likely in infants who failed their first screening bilaterally
      (21.2%) than unilaterally (4.4%); P = .03). CONCLUSIONS: Among healthy newborns,
      delaying AABR screening in the first 48 hours minimized failure rates. SNHL was 6
      times as likely in infants who failed their final screening at >=48 hours
      compared with those who were screened at <48 hours of age. In our study, we offer
      guidance for nursery directors and audiologists who determine hearing screening
      protocols and counsel families about results.

PMID- 29472246
TI  - Counteracting the effects of TNF receptor-1 has therapeutic potential in
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia, and
      neuroinflammation is an important hallmark of the pathogenesis. Tumor necrosis
      factor (TNF) might be detrimental in AD, though the results coming from clinical
      trials on anti-TNF inhibitors are inconclusive. TNFR1, one of the TNF signaling
      receptors, contributes to the pathogenesis of AD by mediating neuronal cell
      death. The blood-cerebrospinal fluid (CSF) barrier consists of a monolayer of
      choroid plexus epithelial (CPE) cells, and AD is associated with changes in CPE
      cell morphology. Here, we report that TNF is the main inflammatory upstream
      mediator in choroid plexus tissue in AD patients. This was confirmed in two
      murine AD models: transgenic APP/PS1 mice and intracerebroventricular (icv)
      AbetaO injection. TNFR1 contributes to the morphological damage of CPE cells in
      AD, and TNFR1 abrogation reduces brain inflammation and prevents blood-CSF
      barrier impairment. In APP/PS1 transgenic mice, TNFR1 deficiency ameliorated
      amyloidosis. Ultimately, genetic and pharmacological blockage of TNFR1 rescued
      from the induced cognitive impairments. Our data indicate that TNFR1 is a
      promising therapeutic target for AD treatment.

PMID- 29472248
TI  - Introducing preLights: preprint highlights, selected by the biological community.

PMID- 29472247
TI  - Time-varying effects of prognostic factors associated with long-term survival in
      breast cancer.
AB  - The impact of some prognostic factors on breast cancer survival has been shown to
      vary with time since diagnosis. However, this phenomenon has not been evaluated
      in Asians. In the present study, 4886 patients were recruited from the Shanghai
      Breast Cancer Survival Study, a longitudinal study of patients diagnosed during
      2002-2006, with a median follow-up time of 11.2 years. Cox model incorporating
      time-by-covariate interactions was used to describe the time-varying effects of
      prognostic factors related to overall survival and disease-free survival. Age
      >=65 years showed a progressively negative effect on breast cancer prognosis over
      time, whereas tumour size >2 cm had a lasting and constant impact. Age
      significantly modified the effects of the tumour grade, nodal status and
      oestrogen receptor (ER) status on breast cancer survival. The detrimental effect
      of poorly differentiated tumours was time limited and more obvious in patients
      aged 45-54 years. Having >=4 positive lymph nodes had a persistent and negative
      impact on prognosis, although it attenuated in later years; the phenomenon was
      more prominent in the 55-64-year age group. ER-positive status was protective in
      the first 3 years after diagnosis but was related to a higher risk of recurrence
      in later years; the time-point when ER-positive status turned into a risk factor
      was earlier in younger patients. These results suggest that older age, positive
      lymph node status, larger tumour size and ER-positive status are responsible for
      late death or recurrence in Asian breast cancer survivors. Extended endocrine
      therapy should be given earlier in younger ER-positive patients.

PMID- 29472245
TI  - Mitotic and Meiotic Functions for the SUMOylation Pathway in the Caenorhabditis
      elegans Germline.
AB  - Meiosis is a highly regulated process, partly due to the need to break and then
      repair DNA as part of the meiotic program. Post-translational modifications are
      widely used during meiotic events to regulate steps such as protein complex
      formation, checkpoint activation, and protein attenuation. In this paper, we
      investigate how proteins that are obligatory components of the SUMO (small
      ubiquitin-like modifier) pathway, one such post-translational modification,
      affect the Caenorhabditis elegans germline. We show that UBC-9, the E2
      conjugation enzyme, and the C. elegans homolog of SUMO, SMO-1, localize to
      germline nuclei throughout prophase I. Mutant analysis of smo-1 and ubc-9
      revealed increased recombination intermediates throughout the germline,
      originating during the mitotic divisions. SUMOylation mutants also showed late
      meiotic defects including defects in the restructuring of oocyte bivalents and
      endomitotic oocytes. Increased rates of noninterfering crossovers were observed
      in ubc-9 heterozygotes, even though interfering crossovers were unaffected. We
      have also identified a physical interaction between UBC-9 and DNA repair protein
      MRE-11 ubc-9 and mre-11 null mutants exhibited similar phenotypes at germline
      mitotic nuclei and were synthetically sick. These phenotypes and genetic
      interactions were specific to MRE-11 null mutants as opposed to RAD-50 or
      resection-defective MRE-11 We propose that the SUMOylation pathway acts
      redundantly with MRE-11, and in this process MRE-11 likely plays a structural
      role.

PMID- 29472249
TI  - Improved Murine MHC-Deficient HLA Transgenic NOD Mouse Models for Type 1 Diabetes
      Therapy Development.
AB  - Improved mouse models for type 1 diabetes (T1D) therapy development are needed.
      T1D susceptibility is restored to normally resistant NOD.beta2m-/- mice
      transgenically expressing human disease-associated HLA-A*02:01 or HLA-B*39:06
      class I molecules in place of their murine counterparts. T1D is dependent on
      pathogenic CD8+ T-cell responses mediated by these human class I variants.
      NOD.beta2m-/--A2.1 mice were previously used to identify beta-cell autoantigens
      presented by this human class I variant to pathogenic CD8+ T cells and for
      testing therapies to attenuate such effectors. However, NOD.beta2m-/- mice also
      lack nonclassical MHC I family members, including FcRn, required for antigen
      presentation, and maintenance of serum IgG and albumin, precluding therapies
      dependent on these molecules. Hence, we used CRISPR/Cas9 to directly ablate the
      NOD H2-Kd and H2-Db classical class I variants either individually or in tandem
      (cMHCI-/-). Ablation of the H2-Ag7 class II variant in the latter stock created
      NOD mice totally lacking in classical murine MHC expression (cMHCI/II-/-). NOD
      cMHCI-/- mice retained nonclassical MHC I molecule expression and FcRn activity.
      Transgenic expression of HLA-A2 or -B39 restored pathogenic CD8+ T-cell
      development and T1D susceptibility to NOD-cMHCI-/- mice. These next-generation
      HLA-humanized NOD models may provide improved platforms for T1D therapy
      development.

PMID- 29472250
TI  - Tau protein liquid-liquid phase separation can initiate tau aggregation.
AB  - The transition between soluble intrinsically disordered tau protein and
      aggregated tau in neurofibrillary tangles in Alzheimer's disease is unknown.
      Here, we propose that soluble tau species can undergo liquid-liquid phase
      separation (LLPS) under cellular conditions and that phase-separated tau droplets
      can serve as an intermediate toward tau aggregate formation. We demonstrate that
      phosphorylated or mutant aggregation prone recombinant tau undergoes LLPS, as
      does high molecular weight soluble phospho-tau isolated from human Alzheimer
      brain. Droplet-like tau can also be observed in neurons and other cells. We found
      that tau droplets become gel-like in minutes, and over days start to
      spontaneously form thioflavin-S-positive tau aggregates that are competent of
      seeding cellular tau aggregation. Since analogous LLPS observations have been
      made for FUS, hnRNPA1, and TDP43, which aggregate in the context of amyotrophic
      lateral sclerosis, we suggest that LLPS represents a biophysical process with a
      role in multiple different neurodegenerative diseases.

PMID- 29472251
TI  - Secondary stroke prevention services in Canada: a cross-sectional survey and
      geospatial analysis of resources, capacity and geographic access.
AB  - BACKGROUND: Rapid assessment and management of transient ischemic attacks and
      nondisabling strokes by specialized stroke prevention services reduces the risk
      of recurrent stroke and improves outcomes. In Canada, with its vast geography and
      with 16.8% of the population living in rural areas, access to these services is
      challenging, and considerable variation in access to care exists. The purpose of
      this multiphase study was to identify sites across Canada providing stroke
      prevention services, evaluate resource capacity and determine geographic access
      for Canadians. METHODS: We developed a Stroke Prevention Services Resource
      Inventory that contained 22 questions on the organization and delivery of stroke
      prevention services and quality monitoring. The inventory ran from November 2015
      to January 2016 and was administered online. We conducted a geospatial analysis
      to estimate access by drive times. Considerations were made for hours of
      operation and access within and across provincial borders. RESULTS: A total of
      123 stroke prevention sites were identified, of which 119 (96.7%) completed the
      inventory. Most (95) are designated stroke prevention or rapid assessment
      clinics. Of the 119 sites, 68 operate full time, and 39 operate less than 2.5
      days per week. A total of 87.3% of the Canadian population has access to a stroke
      prevention service within a 1-hour drive; however, only 69.2% has access to a
      service that operates 5-7 days a week. Allowing provincial border crossing
      improves access (< 6-h drive) for those who are beyond a 6-hour drive within
      their home province (3.4%). INTERPRETATION: Most Canadians have reasonable
      geographic access to stroke prevention services. Allowing patients to cross
      borders improves the existing access for many, particularly some remote
      communities along the Ontario-Quebec and British Columbia-Alberta borders.

PMID- 29472252
TI  - N_LyST: a simple and rapid screening test for Lynch syndrome.
AB  - AIMS: We sought to use PCR followed by high-resolution melting analysis to
      develop a single closed-tube screening panel to screen for Lynch syndrome. This
      comprises tests for microsatellite instability (MSI), MLH1 methylation promoter
      and BRAF mutation. METHODS: For MSI testing, five mononucleotide markers (BAT25,
      BAT26, BCAT25, MYB, EWSR1) were developed. In addition, primers were designed to
      interrogate Region C of the MLH1 promoter for methylation (using bisulphite
      modified DNA) and to test for mutations in codon 600 of BRAF. Two separate
      cohorts from Nottingham (n=99, 46 with MSI, 53 being microsatellite stable (MSS))
      and Edinburgh (n=88, 45 MSI, 43 MSS) were tested. RESULTS: All the cases (n=187)
      were blind tested for MSI and all were correctly characterised by our panel. The
      MLH1 promoter and BRAF were tested only in the Nottingham cohort. Successful
      blinded analysis was performed on the MLH1 promoter in 97 cases. All MSS cases
      showed a pattern of non-methylation while 41/44 cases with MSI showed full
      methylation. The three cases with MSI and a non-methylated pattern had
      aberrations in MSH2 and MSH6 expression. BRAF mutation was detected in 61% of MSI
      cases and 11% of MSS cases.Finally, 12 cases were blind screened by using the
      whole panel as a single test. Of these, five were identified as MSS, four as
      MSI/non-LS and three as MSI/possible LS. These results were concordant with the
      previous data. CONCLUSION: We describe the Nottingham Lynch Syndrome Test
      (N_LyST). This is a quick, simple and cheap method for screening for Lynch
      syndrome.

PMID- 29472253
TI  - Is smoking a risk factor for tinnitus? A systematic review, meta-analysis and
      estimation of the population attributable risk in Germany.
AB  - OBJECTIVE: To assess the epidemiological association of smoking status and
      tinnitus with a systematic review and meta-analysis and to estimate the
      population attributable risk in Germany. DATA SOURCES: A systematic literature
      search in PubMed and ISI-Web of Science Core Collection resulted in 1026 articles
      that were indexed until 15 September 2015. Additionally, proceedings of the
      international tinnitus seminars and reference lists of relevant articles were
      screened. STUDY SELECTION: Two reviewers searched independently for
      epidemiological studies. Tinnitus as a manifestation of tumours, vascular
      malformations, specific syndromes or as a consequence of surgical and medical
      treatment was not considered. Moreover, studies conducted among patients of ear,
      nose and throat clinics were excluded. DATA EXTRACTION: If only raw data were
      provided, effect sizes were calculated. Further unpublished data were received by
      corresponding authors. DATA SYNTHESIS: Data of 20 studies were pooled. Current
      smoking (OR 1.21, 95% CI 1.09 to 1.35), former smoking (OR 1.13, 95% CI 1.01 to
      1.26) and ever smoking (OR 1.20, 95% CI 1.11 to 1.30) were significantly
      associated with tinnitus. Moreover, sensitivity analyses for severe tinnitus (OR
      1.32, 95% CI 1.10 to 1.58) and for studies of superior quality (OR 1.15, 95% CI
      1.03 to 1.29) showed increased risks. According to this, the population
      attributable risk estimate in Germany is 3.5%. CONCLUSION: There is sufficient
      evidence that smoking is associated with tinnitus. As the review mainly consists
      of cross-sectional studies, the observed correlation does not give evidence of a
      causal relationship. Due to the impact of various confounders, further research
      is needed to provide more evidence on the strength of association and causal
      relationships.

PMID- 29472254
TI  - Comparison of new-generation drug-eluting stents versus drug-coated balloon for
      in-stent restenosis: a meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: The study sought to compare angiographic and clinical outcomes of new
      generation drug-eluting stents (DES) versus drug-coated balloon (DCB) in patients
      with coronary in-stent restenosis (ISR). DESIGN: Meta-analysis using data from
      randomised trial found by searches on PubMed, the Cochrane Library,
      ClinicalTrials.gov and websites of major cardiovascular congresses. SETTING: Only
      randomised trials comparing DES with DCB were included. PARTICIPANTS: Patients
      with ISR in the included trials. INTERVENTIONS: New-generation DES versus DCB.
      OUTCOMES: The angiographic and clinical outcomes including cardiac death, all
      cause death, myocardial infarction, target lesion revascularisation (TLR), target
      vessel revascularisation (TVR), major adverse cardiac events (MACE) and stent
      thrombosis were investigated. RESULTS: Five trials including 913 patients were
      eligible and included. Pooled analysis in angiographic results identified that
      new-generation DES were associated with higher acute luminal gain (-0.31 mm, 95%
      CI -0.42 to -0.20, P<0.001) and lower per cent diameter stenosis (risk ratio
      (RR): 0.28, 95% CI 0.02 to 0.55, P=0.04). DES significantly reduced the risk of
      TLR (RR: 1.96, 95% CI 1.17 to 3.28, P=0.01) compared with DCB; however, there was
      no statistical differences for MACE (RR: 1.21, 95% CI 0.67 to 2.17, P=0.53),
      myocardial infarction (RR: 1.16, 95% CI 0.55 to 2.48, P=0.69) and cardiac death
      (RR: 1.80, 95% CI 0.60 to 5.39, P=0.29). CONCLUSIONS: Interventions with new
      generation DES appear to be associated with significant reduction in per cent
      diameter stenosis and TLR at short-term follow-up, but had similar MACE,
      myocardial infarction and cardiac death for patients with coronary ISR compared
      with DCB. Appropriately powered studies with longer term follow-up are warranted
      to confirm these findings.

PMID- 29472255
TI  - Comparison of a newly established emotional stimulus approach to a classical
      assessment-driven approach in BLS training: a randomised controlled trial.
AB  - OBJECTIVE: The study objective was to implement two strategies (short emotional
      stimulus vs announced practical assessment) in the teaching of resuscitation
      skills in order to evaluate whether one led to superior outcomes. SETTING: This
      study is an educational intervention provided in one German academic university
      hospital. PARTICIPANTS: First-yearmedical students (n=271) during the first3
      weeks of their studies. INTERVENTIONS: Participants were randomly assigned to one
      of two groups following a sequence of random numbers: the emotional stimulus
      group (EG) and the assessment group (AG). In the EG, the intervention included
      watching an emotionally stimulating video prior to the Basic Life Support (BLS)
      course. In the AG, a practical assessment of the BLS algorithm was announced and
      tested within a 2 min simulated cardiac arrest scenario. After the baseline
      testing, a standardised BLS course was provided. Evaluation points were defined 1
      week and 6 months after. PRIMARY OUTCOME MEASURES: Compression depth (CD) and
      compression rate (CR) were recorded as the primary endpoints for BLS quality.
      RESULTS: Within the study, 137 participants were allocated to the EG and 134 to
      the AG. 104 participants from EG and 120 from AG were analysed1 week after the
      intervention, where they reached comparable chest-compression performance without
      significant differences (CR P=0.49; CD P=0.28). The chest-compression performance
      improved significantly for the EG (P<0.01) and the AG (P<0.01) while adhering to
      the current resuscitation guidelines criteria for CD and CR. CONCLUSIONS: There
      was no statistical difference between both groups' practical chest-compression
      performance. Nevertheless, the 2 min video sequence used in the EG with its low
      production effort and costs, compared with the expensive assessment approach,
      provides broad opportunities for applicability in BLS training.

PMID- 29472256
TI  - Protocol for a longitudinal twin birth cohort study to unravel the complex
      interplay between early-life environmental and genetic risk factors in health and
      disease: the Chongqing Longitudinal Twin Study (LoTiS).
AB  - INTRODUCTION: Non-communicable diseases (NCD) now represent the major burden of
      adverse health in most countries. It is clear that much of the risk of such
      conditions begins very early in life, potentially in utero. Given their complex
      aetiology, an understanding of the origins of NCD requires an in-depth analysis
      of the interplay between genetic variation and environment, preferably over time.
      For decades, twin studies have played a key role in understanding such traits.
      Their strength lies in the ability to disentangle genetic and environmental
      factors that contribute to a phenotype. This is done by comparing genetically
      identical monozygotic (MZ) with dizygotic twins, who share on average 50% of
      genetic variation, or by comparing MZ twins within a pair. This study aims to
      determine the relative contributions of genes and environment to early-onset
      intermediate phenotypes related to later adult onset disease (such as growth and
      neurodevelopment) and to identify specific biomarkers and time points for
      emergence of phenotypes from infancy, largely independent of underlying genetic
      factors. METHODS/DESIGN: The Chongqing Longitudinal Twin Study (LoTiS) will
      recruit 300 women pregnant with twins, enriched for MZ pregnancies, with follow
      up to 3 years of age. Data collection will be undertaken at key time points in
      gestation (*3), at delivery and postnatally (*9). Maternal and infant
      biospecimens including blood, urine, hair, nails and buccal swabs along with
      measures such as fetal scans and body measurements will be collected. Additional
      information from questionnaires and medical records includes pregnancy, diet,
      sociodemographics, maternal stress, and infant growth and neurodevelopment.
      ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of
      Chongqing Medical University (record no: 201530) and has been registered with the
      Chinese Clinical Trial Registry (registry no: ChiCTR-OOC-16008203). Results of
      the recruitment and all subsequent analyses will be submitted for publication in
      peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR-OOC-16008203; Results.

PMID- 29472257
TI  - Dementia prevalence in a population at high vascular risk: the Trinidad national
      survey of ageing and cognition.
AB  - OBJECTIVE: To investigate the dementia prevalence in a country with high levels
      of cardiovascular risk factors DESIGN AND METHODS: Older people in Trinidad are
      recognised to have particularly high levels of cardiovascular risk factors. We
      carried out a survey in a nationally representative sample of people aged >=70
      years using household enumeration. Dementia status was ascertained using
      standardised interviews and algorithms from the 10/66 schedule and age-specific
      prevalence were compared with identically defined output from the 10/66 surveys
      of 16 536 residents in eight other low-income and middle-income countries.
      RESULTS: Of 1832 participants (77.0% response rate), dementia was present in 442
      (23.4%). Prevalences were 12.0% in persons aged 70-74 years, 23.5% at 75-79,
      25.8% at 80-84, 41.3% at 85-89 and 54.0% in those aged >=90 years. Prevalence
      ratios compared with averages from 10/66 surveys in these age groups were 2.2,
      2.6, 1.6, 1.7 and 1.6, respectively, and were 2.7, 2.8, 1.7, 1.4 and 0.8,
      respectively, compared with previously published consensus estimates for the
      Latin American region. Dementia was significantly associated with reported stroke
      and diabetes in logistic regression models adjusted for sociodemographic status
      and other vascular risk factors (OR (95% CI) 4.40 (2.70 to 7.19) and 1.56 (1.20
      to 2.03), respectively). Projected national numbers of people with dementia (18
      206) were 70%-100% higher than those estimated using most recent regional
      consensus prevalences. CONCLUSION: In a nation with high levels of vascular risk,
      dementia prevalence is higher than expected, particularly at the lower end of the
      70+ age range. International prevalence projections may need to take into account
      risk status as well as age structures.

PMID- 29472258
TI  - Compassionate care intervention for hospital nursing teams caring for older
      people: a pilot cluster randomised controlled trial.
AB  - OBJECTIVE: Compassionate care continues to be a focus for national and
      international attention, but the existing evidence base lacks the experimental
      methodology necessary to guide the selection of effective interventions for
      practice. This study aimed to evaluate the Creating Learning Environments for
      Compassionate Care (CLECC) intervention in improving compassionate care. SETTING:
      Ward nursing teams (clusters) in two English National Health Service hospitals
      randomised to intervention (n=4) or control (n=2). Intervention wards comprised
      two medicines for older people (MOPs) wards and two medical/surgical wards.
      Control wards were both MOPs. PARTICIPANTS: Data collected from 627 patients and
      178 staff. EXCLUSION CRITERIA: reverse barrier nursed, critically ill, palliative
      or non-English speaking. All other patients and all nursing staff and Health Care
      Assistant HCAs were invited to participant, agency and bank staff were excluded.
      INTERVENTION: CLECC, a workplace intervention focused on developing sustainable
      leadership and work-team practices to support the delivery of compassionate care.
      CONTROL: No educational activity. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary
      Quality of Interaction Schedule (QuIS) for observed staff-patient interactions.
      Secondary-patient-reported evaluations of emotional care in hospital (PEECH);
      nurse-reported empathy (Jefferson Scale of Empathy). RESULTS: Trial proceeded as
      per protocol, randomisation was acceptable. Some but not all blinding strategies
      were successful. QuIS observations achieved 93% recruitment rate with 25% of
      patient sample cognitively impaired. At follow-up there were more total positive
      (78% vs 74%) and less total negative (8% vs 11%) QuIS ratings for intervention
      wards versus control wards. Sixty-three per cent of intervention ward patients
      scored lowest (ie, more negative) scores on PEECH connection subscale, versus 79%
      of control. This was not a statistically significant difference. No statistically
      significant differences in nursing empathy were observed. CONCLUSIONS: Use of
      experimental methods is feasible. The use of structured observation of staff
      patient interaction quality is a promising outcome measure inclusive of hard to
      reach groups. TRIAL REGISTRATION NUMBER: ISRCTN16789770.

PMID- 29472259
TI  - Feasibility of a multicentre, randomised controlled trial of laparoscopic versus
      open colorectal surgery in the acute setting: the LaCeS feasibility trial
      protocol.
AB  - INTRODUCTION: Acute colorectal surgery forms a significant proportion of
      emergency admissions within the National Health Service. There is limited
      evidence to suggest minimally invasive surgery may be associated with improved
      clinical outcomes in this cohort of patients. Consequently, there is a need to
      assess the clinical effectiveness and cost-effectiveness of laparoscopic surgery
      in the acute colorectal setting. However,emergency colorectal surgical trials
      have previously been difficult to conduct due to issues surrounding recruitment
      and equipoise. The LaCeS (randomised controlled trial of Laparoscopic versus open
      Colorectal Surgery in the acute setting) feasibility trial will determine the
      feasibility of conducting a definitive, phase III trial of laparoscopic versus
      open acute colorectal resection. METHODS AND ANALYSIS: The LaCeS feasibility
      trial is a prospective, multicentre, single-blinded, parallel group, pragmatic
      randomised controlled feasibility trial. Patients will be randomised on a 1:1
      basis to receive eitherlaparoscopic or open surgery. The trial aims to recruit at
      least 66 patients from five acute general surgical units across the UK. Patients
      over the age of 18 with a diagnosis of acute colorectal pathology requiring
      resection on clinical and radiological/endoscopic investigations, with a National
      Confidential Enquiry into Patient Outcome and Death classification of urgent will
      be considered eligible for participation. The primary outcome is recruitment.
      Secondary outcomes include assessing the safety profile of laparoscopic surgery
      using intraoperative and postoperative complication rates, conversion rates and
      patient-safety indicators as surrogate markers. Clinical and patient-reported
      outcomes will also be reported. The trial will contain an embedded qualitative
      study to assess clinician and patient acceptability of trial processes. ETHICS
      AND DISSEMINATION: The LaCeS feasibility trial is approved by the Yorkshire and
      The Humber, Bradford Leeds Research Ethics Committee (REC reference: 15/
      YH/0542). The results from the trial will be presented at national and
      international colorectal conferences and will be submitted for publication to
      peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN15681041; Pre-results.

PMID- 29472260
TI  - Exploring the relationship between local food environments and obesity in UK,
      Ireland, Australia and New Zealand: a systematic review protocol.
AB  - INTRODUCTION: Obesity is a global pandemic that affects all socioeconomic strata,
      however, the highest figures have been observed in the most disadvantaged social
      groups. Evidence from the USA and Canada showed that specific urban settings
      encourage obesogenic behaviour in the population living and/or working there. We
      aim to examine the evidence on the association between local food environments
      and obesity in the UK, Ireland, Australia and New Zealand. METHODS: Six databases
      from 1990 to 2017 will be searched: MEDLINE (Ovid), Embase (Ovid), Scopus, The
      Cumulative Index to Nursing and Allied Health Literature (CINAHL), Applied Social
      Sciences Index and Abstracts (ASSIA) and Web of Science. Grey literature will
      also be sought by searching Opengrey Europe, The Grey Literature Report and
      relevant government websites. Additional studies will be retrieved from the
      reference lists of the selected articles. It will include cohort, longitudinal,
      case study and cross-sectional studies that have assessed the relationship
      between local food environments and obesity in the UK, Ireland, Australia and New
      Zealand regardless of sex, age and ethnicity of the population. Two researchers
      will independently select the studies and extract the data. Data items will
      incorporate: author names, title, study design, year of study, year exposure data
      collected, country, city, urban/rural, age range, study exclusions, special
      characteristics of study populations, aims, working definitions of food
      environments and food outlets, exposure and methods of data collection, outcomes
      and key findings. A narrative synthesis and a summary of the results will be
      produced separately for children and adults, according to the type of food
      exposure-outcome. All the selected studies will be assessed using The Quality
      Assessment Tool for Observational Cohort and Cross-Sectional Studies. ETHICS AND
      DISSEMINATION: This study will be based on published literature, and therefore
      ethical approval has not been sought. Our findings will be presented at relevant
      national and international scientific conferences and published in a peer
      reviewed journal.

PMID- 29472261
TI  - Development and validation of the Swedish national stroke register Riksstroke's
      questionnaires in patients at 3 and 12 months after stroke: a qualitative study.
AB  - OBJECTIVES: Because healthcare and community organisations and treatment methods
      are always changing, continuous changes might also be needed in questionnaires
      that register patient-reported outcomes (PRO) and patient-reported experiences
      (PRE) of healthcare interventions and community support. Thus, the aim of this
      study was to test the content and face validity, including the readability, of
      two questionnaires used by the Swedish national stroke register Riksstroke to
      register PRO and PRE at 3 and 12 months poststroke. DESIGN: Clinicians' and
      patients' knowledge and experiences of current care, rehabilitation, community
      support and functioning after stroke as well as comments noted regarding the
      content and layout of the questionnaires were retrieved in focus-groups with
      expert clinicians and in patient interviews analysed with content analysis. A
      workgroup of experts with experience in stroke care, rehabilitation and research
      repeatedly revised the questionnaires regarding content, layout and consistency
      throughout the validation process. PARTICIPANTS: The participants included allied
      healthcare professionals, nurses and physicians with extensive experience of
      working with stroke care and rehabilitation (expert clinicians) as well as
      patients who had suffered a stroke 3 or 12 months earlier and who were
      purposefully selected among those who had completed and returned the 3-month
      questionnaire. SETTING: Expert clinicians met at their work place in focus
      groups. Patients were interviewed where they resided, that is, in their home or
      nursing home, including rural, town and city areas in Sweden. RESULTS: Based on
      clinical expertise and comments from the patients (n=47), the questionnaires were
      revised and then found to be valid in terms of content validity and face
      validity, including readability. CONCLUSIONS: The present evaluation emphasises
      the need for testing aspects of validity, including readability, of
      questionnaires addressing PRO and PRE and for the recurrent revision of such
      questionnaires in order to maintain their validity in a society undergoing
      constant change.

PMID- 29472262
TI  - A prospective cohort study to investigate parental stress and child health in low
      income Chinese families: protocol paper.
AB  - INTRODUCTION: Chronic stress has adverse effects on health. Adults and children
      from low-income families are subject to multiple sources of stress. Existing
      literature about economic hardship mostly focuses on either adults or children
      but not both. Moreover, there is limited knowledge on the relationship between
      parental generalised stress and child health problems. This study aims to explore
      the bidirectional relationship between parental stress and child health in
      Chinese low-income families and to identify other modifiable factors influencing
      this relationship. METHODS AND ANALYSIS: This prospective cohort study will
      sample 254 low-income parent-child pairs and follow them up for 24 months with
      assessments at three time points (baseline, 12 and 24 months) on parental stress,
      health-related quality of life (HRQOL) and child health and behaviour using both
      subjective measures and objective physiological parameters. This study will
      collect data using standardised measures on HRQOL and behaviours of children as
      well as on HRQOL, mental health and stress levels of parents along with
      physiological tests of allostatic load and telomere length. The mediating or
      moderating effect of family harmony, parenting style and neighbourhood conditions
      will also be assessed. Data will be analysed using latent growth modelling and
      cross-lagged path analysis modelling to examine the bidirectional effect of
      parental stress and child health over time. Mediation and moderation analysis
      will also be conducted to examine the mechanism by which the variables relate.
      ETHICS AND DISSEMINATION: This study was approved by the institutional review
      board of the University of Hong Kong-the Hospital Authority Hong Kong West
      Cluster, reference no: UW 16-415. The study findings will be disseminated through
      peer-reviewed publications and international conferences. TRIAL REGISTRATION
      NUMBER: NCT03185273; Pre-results.

PMID- 29472263
TI  - Defining a set of standardised outcome measures for newly diagnosed patients with
      multiple myeloma using the Delphi consensus method: the IMPORTA project.
AB  - OBJECTIVE: To define a standard set of outcomes and the most appropriate
      instruments to measure them for managing newly diagnosed patients with multiple
      myeloma (MM). METHODS: A literature review and five discussion groups facilitated
      the design of two-round Delphi questionnaire. Delphi panellists (haematologists,
      hospital pharmacists and patients) were identified by the scientific committee,
      the Spanish Program of Haematology Treatments Foundation, the Spanish Society of
      Hospital Pharmacies and the Spanish Community of Patients with MM. Panellist's
      perception about outcomes' suitability and feasibility of use was assessed on a
      seven-point Likert scale. Consensus was reached when at least 75% of the
      respondents reached agreement or disagreement. A scientific committee led the
      project. RESULTS: Fifty-one and 45 panellists participated in the first and
      second Delphi rounds, respectively. Consensus was reached to use overall
      survival, progression-free survival, minimal residual disease and treatment
      response to assess survival and disease control. Panellists agreed to measure
      health-related quality of life, pain, performance status, fatigue, psychosocial
      status, symptoms, self-perception on body image, sexuality and
      preferences/satisfaction. However, panellist did not reach consensus about the
      feasibility of assessing in routine practice psychosocial status, symptoms, self
      perception on body image and sexuality. Consensus was reached to collect patient
      reported outcomes through the European Organisation for the Research and
      Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core
      questionnaire 30 (C30), three items from EORTC-QLQ-Multiple Myeloma (MY20) and
      EORTC-QLQ-Breast Cancer (BR23), pain Visual Analogue Scale, Morisky-Green and ad
      hoc questions about patients' preferences/satisfaction. CONCLUSIONS: A consensual
      standard set of outcomes for managing newly diagnosed patients with MM has been
      defined. The feasibility of its implementation in routine practice will be
      assessed in a future pilot study.

PMID- 29472264
TI  - Cost-effectiveness of mechanical thrombectomy within 6 hours of acute ischaemic
      stroke in China.
AB  - OBJECTIVES: Endovascular mechanical thrombectomy is an effective but expensive
      therapy for acute ischaemic stroke with proximal anterior circulation occlusion.
      This study aimed to determine the cost-effectiveness of mechanical thrombectomy
      in China, which is the largest developing country. DESIGN: A combination of
      decision tree and Markov model was developed. Outcome and cost data were derived
      from the published literature and claims database. The efficacy data were derived
      from the meta-analyses of nine trials. One-way and probabilistic sensitivity
      analyses were performed in order to assess the uncertainty of the results.
      SETTING: Hospitals in China. PARTICIPANTS: The patients with acute ischaemic
      stroke caused by proximal anterior circulation occlusion within 6 hours.
      INTERVENTIONS: Mechanical thrombectomy within 6 hours with intravenous tissue
      plasminogen activator (tPA) treatment within 4.5 hours versus intravenous tPA
      treatment alone. OUTCOME MEASURES: The benefit conferred by the treatment was
      assessed by estimating the cost per quality-adjusted life-year (QALY) gained in
      the long term (30 years). RESULTS: The addition of mechanical thrombectomy to
      intravenous tPA treatment compared with standard treatment alone yielded a
      lifetime gain of 0.794 QALYs at an additional cost of CNY 50 000 (US$7700),
      resulting in a cost of CNY 63 010 (US$9690) per QALY gained. The probabilistic
      sensitivity analysis indicated that mechanical thrombectomy was cost-effective in
      99.9% of the simulation runs at a willingness-to-pay threshold of CNY 125 700
      (US$19 300) per QALY. CONCLUSIONS: Mechanical thrombectomy for acute ischaemic
      stroke caused by proximal anterior circulation occlusion within 6 hours was cost
      effective in China. The data may be used as a reference with regard to medical
      resources allocation for stroke treatment in low-income and middle-income
      countries as well as in the remote areas in the developed countries.

PMID- 29472265
TI  - Does early vitamin B12 supplementation improve neurodevelopment and cognitive
      function in childhood and into school age: a study protocol for extended follow
      ups from randomised controlled trials in India and Tanzania.
AB  - INTRODUCTION: As many as 250 million children under the age of 5 may not be
      reaching their full developmental potential partly due to poor nutrition during
      pregnancy and the first 2 years of life. Micronutrients, including vitamin B12,
      are important for the development of brain structure and function; however, the
      timing, duration and severity of deficiencies may alter the impact on functional
      development outcomes. Consequently, to fully explore the effect of vitamin B12 on
      cognitive function, it is crucial to measure neurodevelopment at different ages,
      in different populations and with vitamin B12 supplementation at different times
      during the critical periods of neurodevelopment. METHODS AND ANALYSIS: In this
      project, we follow up children from four recently completed randomised placebo
      controlled trials of oral vitamin B12 supplementation, two in India and two in
      Tanzania, to explore the long-term effects on neurodevelopmental outcomes and
      growth. All the included trials provided at least two recommended dietary
      allowances of oral vitamin B12 daily for at least 6 months. Vitamin B12 was
      supplemented either during pregnancy, early infancy or early childhood. Primary
      outcomes are neurodevelopmental status, cognitive function and growth later in
      childhood. We apply validated and culturally appropriate instruments to identify
      relevant developmental outcomes. All statistical analyses will be done according
      to intention-to-treat principles. The project provides an excellent opportunity
      to examine the effect of vitamin B12 supplementation in different periods during
      early life and measure the outcomes later in childhood. ETHICS AND DISSEMINATION:
      The study has received ethical approvals from all relevant authorities in Norway,
      USA, Tanzania and India and complies fully with ethical principles for medical
      research. Results will be presented at national and international research and
      policy meetings and published in peer-reviewed scientific journals, preferably
      open access. TRIAL REGISTRATION NUMBER: NCT00641862 (Bangalore); NCT00717730,
      updated CTRI/2016/11/007494 (Delhi); NCT00197548 and NCT00421668 (Dar es Salaam).

PMID- 29472266
TI  - Long-term mortality in outpatients with type 2 diabetes in a reference hospital
      in Cameroon: a retrospective cohort study.
AB  - OBJECTIVES: There are limited data on mortality in patients with type 2 diabetes
      mellitus (T2DM) in Sub-Saharan Africa. We aimed at determining the mortality
      rate, and the causes and the predictors of death in patients with T2DM followed
      as outpatients in a reference hospital in Cameroon. DESIGN: Retrospective cohort
      study. SETTING: A reference hospital in Cameroon. PARTICIPANTS: From December
      2015 to March 2016, patients with T2DM aged 18 years and older and who consulted
      between January 2009 and December 2014, were contacted directly or through their
      next of kin, and included in this study. All participants with less than 75% of
      desired data in files, those who could not be reached on the phone and those who
      refused to provide consent were excluded from the study. Of the 940 eligible
      patients, 628 (352 men and 276 women) were included and completed the study,
      giving a response rate of 66.8%. OUTCOME MEASURES: Death rate, causes of death
      and predictors of death. RESULTS: Of the 628 patients (mean age: 56.5 years;
      median diabetes duration: 3.5 years) followed up for a total of 2161 person
      years, 54 died, giving a mortality rate of 2.5 per 100 person-years and a
      cumulative mortality rate of 8.6%. Acute metabolic complications (22.2%),
      cardiovascular diseases (16.7%), cancers (14.8%), nephropathy (14.8%) and
      diabetic foot syndrome (13.0%) were the most common causes of death. Advanced age
      (adjusted HR (aHR) 1.06, 95% CI 1.02 to 1.10; P=0.002), raised glycated
      haemoglobin (HbA1c) (aHR 1.16, 95% CI 1.00 to 1.35; P=0.051), low blood
      haemoglobin (aHR 1.06, 95% CI 1.02 to 1.10; P=0.002) and proteinuria (aHR 2.97,
      95% CI 1.40 to 6.28; P=0.004) were identified as independent predictors of death.
      CONCLUSIONS: The mortality rate in patients with T2DM is high in our population,
      with acute metabolic complications as the leading cause. Patients with advanced
      age, raised HbA1c, anaemia or proteinuria are at higher risk of death and
      therefore represent the target of interest to prevent mortality in T2DM.

PMID- 29472267
TI  - Measurement properties of the craniocervical flexion test: a systematic review
      protocol.
AB  - INTRODUCTION: Neck pain is the leading cause of years lived with disability
      worldwide and it accounts for high economic and societal burden. Altered
      activation of the neck muscles is a common musculoskeletal impairment presented
      by patients with neck pain. The craniocervical flexion test with pressure
      biofeedback unit has been widely used in clinical practice to assess function of
      deep neck flexor muscles. This systematic review will assess the measurement
      properties of the craniocervical flexion test for assessing deep cervical flexor
      muscles. METHODS AND ANALYSIS: This is a protocol for a systematic review that
      will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis
      statement. MEDLINE (via PubMed), EMBASE, PEDro, Cochrane Central Register of
      Controlled Trials (CENTRAL), Scopus and Science Direct will be systematically
      searched from inception. Studies of any design that have investigated and
      reported at least one measurement property of the craniocervical flexion test for
      assessing the deep cervical flexor muscles will be included. All measurement
      properties will be considered as outcomes. Two reviewers will independently rate
      the risk of bias of individual studies using the updated COnsensus-based
      Standards for the selection of health Measurement Instruments risk of bias
      checklist. A structured narrative synthesis will be used for data analysis.
      Quantitative findings for each measurement property will be summarised. The
      overall rating for a measurement property will be classified as 'positive',
      'indeterminate' or 'negative'. The overall rating will be accompanied with a
      level of evidence. ETHICS AND DISSEMINATION: Ethical approval and patient consent
      are not required since this is a systematic review based on published studies.
      Findings will be submitted to a peer-reviewed journal for publication. PROSPERO
      REGISTRATION NUMBER: CRD42017062175.

PMID- 29472268
TI  - Neuroimaging of headaches in patients with normal neurological examination:
      protocol for a systematic review.
AB  - INTRODUCTION: Headache disorders (HD) are among the most frequent neurological
      disorders seen in neurology practice. Because secondary HD are rare, patients'
      examination is most often unremarkable. However, the will to relieve patients'
      anxiety and the fear of prosecutions lead to overuse of neuroimaging thus
      resulting in the discovery of incidental findings (IF) or normal variants that
      can lead to futile or harmful procedures. Knowing the probability of identifying
      a potentially clinically significant lesion in patients with isolated headache
      could facilitate decision-making and reduce health costs. This review aims to
      determine the prevalence of incidental findings and normal anatomic variants
      (NAV) on neuroimaging studies performed in patients presenting with headache and
      normal neurological examination. METHOD AND ANALYSIS: Studies reporting
      neuroimaging findings in patients with headache and normal neurological
      examination and published before the 30 September 2017 will be identified by
      searching PubMed, Medline and EMBASE (Excerpta Medica Database). Relevant
      unpublished papers and conference proceedings will also be checked. Full texts of
      eligible studies will then be accessed and data extracted using a standard data
      extraction sheet. Studies will be assessed for quality and risk of bias.
      Heterogeneity of studies will be evaluated by the chi2 test on Cochrane's Q
      statistic. The prevalence of NAV and IF across studies and in relevant subgroups
      will be estimated by pooling the study-specific estimates using a random-effects
      meta-analysis. Visual analysis of funnel plot and Egger's test will be used to
      detect publication bias. The report of this systematic review will be compliant
      with the Meta-analysis of Observational Studies in Epidemiology guidelines.
      ETHICS AND DISSEMINATION: The current study is based on published data; ethical
      approval is, therefore, not required. The final report of this systematic review
      will be published in a peer-reviewed journal. Furthermore, findings will be
      presented at conferences and submitted to relevant health authorities. TRIAL
      REGISTRATION NUMBER: CRD42017079714.

PMID- 29472269
TI  - Understanding the gender gap in antibiotic prescribing: a cross-sectional
      analysis of English primary care.
AB  - OBJECTIVES: To explore the causes of the gender gap in antibiotic prescribing,
      and to determine whether women are more likely than men to receive an antibiotic
      prescription per consultation. DESIGN: Cross-sectional analysis of routinely
      collected electronic medical records from The Health Improvement Network (THIN).
      SETTING: English primary care. PARTICIPANTS: Patients who consulted general
      practices registered with THIN between 2013 and 2015. PRIMARY AND SECONDARY
      OUTCOME MEASURES: Total antibiotic prescribing was measured in children (<19
      years), adults (19-64 years) and the elderly (65+ years). For 12 common
      conditions, the number of adult consultations was measured, and the relative risk
      (RR) of being prescribed antibiotics when consulting as female or with
      comorbidity was estimated. RESULTS: Among 4.57 million antibiotic prescriptions
      observed in the data, female patients received 67% more prescriptions than male
      patients, and 43% more when excluding antibiotics used to treat urinary tract
      infection (UTI). These gaps were more pronounced in adult women (99% more
      prescriptions than men; 69% more when excluding UTI) than in children (9%; 0%) or
      the elderly (67%; 38%). Among adults, women accounted for 64% of consultations
      (62% among patients with comorbidity), but were not substantially more likely
      than men to receive an antibiotic prescription when consulting with common
      conditions such as cough (RR 1.01; 95% CI 1.00 to 1.02), sore throat (RR 1.01,
      95% CI 1.00 to 1.01) and lower respiratory tract infection (RR 1.00, 95% CI 1.00
      to 1.01). Exceptions were skin conditions: women were less likely to be
      prescribed antibiotics when consulting with acne (RR 0.67, 95% CI 0.66 to 0.69)
      or impetigo (RR 0.85, 95% CI 0.81 to 0.88). CONCLUSIONS: The gender gap in
      antibiotic prescribing can largely be explained by consultation behaviour.
      Although in most cases adult men and women are equally likely to be prescribed an
      antibiotic when consulting primary care, it is unclear whether or not they are
      equally indicated for antibiotic therapy.

PMID- 29472270
TI  - CRISPR RNAs trigger innate immune responses in human cells.
AB  - Here, we report that CRISPR guide RNAs (gRNAs) with a 5'-triphosphate group (5'
      ppp gRNAs) produced via in vitro transcription trigger RNA-sensing innate immune
      responses in human and murine cells, leading to cytotoxicity. 5'-ppp gRNAs in the
      cytosol are recognized by DDX58, which in turn activates type I interferon
      responses, causing up to ~80% cell death. We show that the triphosphate group can
      be removed by a phosphatase in vitro and that the resulting 5'-hydroxyl gRNAs in
      complex with Cas9 or Cpf1 avoid innate immune responses and can achieve targeted
      mutagenesis at a frequency of 95% in primary human CD4+ T cells. These results
      are in line with previous findings that chemically synthesized sgRNAs with a 5'
      hydroxyl group are much more efficient than in vitro-transcribed (IVT) sgRNAs in
      human and other mammalian cells. The phosphatase treatment of IVT sgRNAs is a
      cost-effective method for making highly active sgRNAs, avoiding innate immune
      responses in human cells.

PMID- 29472271
TI  - TNFalpha and Radioresistant Stromal Cells Are Essential for Therapeutic Efficacy
      of Cyclic Dinucleotide STING Agonists in Nonimmunogenic Tumors.
AB  - The cGAS-STING cytosolic DNA sensing pathway may play an integral role in the
      initiation of antitumor immune responses. Studies evaluating the immunogenicity
      of various cyclic dinucleotide (CDN) STING agonists administered by intratumoral
      (i.t.) injection showed potent induction of inflammation, tumor necrosis, and, in
      some cases, durable tumor-specific adaptive immunity. However, the specific
      immune mechanisms underlying these responses remain incompletely defined. The
      majority of these studies have focused on the effect of CDNs on immune cells but
      have not conclusively interrogated the role of stromal cells in the acute
      rejection of the CDN-injected tumor. Here, we revealed a mechanism of STING
      agonist-mediated tumor response that relied on both stromal and immune cells to
      achieve tumor regression and clearance. Using knockout and bone marrow chimeric
      mice, we showed that although bone marrow-derived TNFalpha was necessary for CDN
      induced necrosis, STING signaling in radioresistant stromal cells was also
      essential for CDN-mediated tumor rejection. These results provide evidence for
      crosstalk between stromal and hematopoietic cells during CDN-mediated tumor
      collapse after i.t. administration. These mechanistic insights may prove critical
      in the clinical development of STING agonists. Cancer Immunol Res; 6(4); 422-33.
      (c)2018 AACR.

PMID- 29472272
TI  - Mutations in XRCC1 cause cerebellar ataxia and peripheral neuropathy.

PMID- 29472274
TI  - Bridging gaps in care: Implementation of a pharmacist-led transitions-of-care
      program.
AB  - PURPOSE: The development and implementation of a hospitalwide, pharmacist-led
      transitions-of-care (TOC) program are described. METHODS: This 21-week quality
      improvement initiative was conducted from October 1, 2015, to February 26, 2016,
      at Memorial Hospital Pembroke. A TOC team was comprised of pharmacists, a
      pharmacy resident, pharmacy students, a physician, case managers, and nurses. All
      patients over the age of 18 admitted to the inpatient telemetry unit were
      included in this initiative. The primary endpoint was a sustained improvement in
      Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores
      for "Communication About Medications" and "Care Transitions: Understood the
      Purpose of Taking Medications." Secondary outcomes included 90% of admission and
      80% of discharge medication reconciliations reviewed by a pharmacist. RESULTS: A
      total of 661 patients were included. The HCAHPS scores for "Communication About
      Medications" and "Care Transitions: Understood the Purpose of Taking Medications"
      had a sustained improvement during the study period. A pharmacist completed 94%
      and 75% of admission and discharge medication reviews, respectively, and a total
      of 1,579 interventions were made. Discharge education was completed at a rate of
      73%. CONCLUSION: After a quality improvement initiative developed by pharmacists
      was implemented, HCAHPS scores showed improvement and more patients received
      medication reconciliation.

PMID- 29472273
TI  - A unified approach for quantifying and interpreting DNA shape readout by
      transcription factors.
AB  - Transcription factors (TFs) interpret DNA sequence by probing the chemical and
      structural properties of the nucleotide polymer. DNA shape is thought to enable a
      parsimonious representation of dependencies between nucleotide positions. Here,
      we propose a unified mathematical representation of the DNA sequence dependence
      of shape and TF binding, respectively, which simplifies and enhances analysis of
      shape readout. First, we demonstrate that linear models based on mononucleotide
      features alone account for 60-70% of the variance in minor groove width, roll,
      helix twist, and propeller twist. This explains why simple scoring matrices that
      ignore all dependencies between nucleotide positions can partially account for
      DNA shape readout by a TF Adding dinucleotide features as sequence-to-shape
      predictors to our model, we can almost perfectly explain the shape parameters.
      Building on this observation, we developed a post hoc analysis method that can be
      used to analyze any mechanism-agnostic protein-DNA binding model in terms of
      shape readout. Our insights provide an alternative strategy for using DNA shape
      information to enhance our understanding of how cis-regulatory codes are
      interpreted by the cellular machinery.

PMID- 29472275
TI  - Comparison of clinical pharmacy specialists and primary care physicians in
      treatment of type 2 diabetes mellitus in rural Veterans Affairs facilities.
AB  - PURPOSE: Results of a study to compare the impact of clinical pharmacy specialist
      (CPS) interventions with primary care physician (PCP) interventions in veterans
      with type 2 diabetes mellitus (T2D) in a rural setting are presented. METHODS: A
      retrospective analysis was performed examining veterans diagnosed with T2D with a
      glycosylated hemoglobin (HbA1c) of >=8% receiving treatment at a rural community
      based outpatient clinic associated with the Memphis Veterans Affairs Medical
      Center. Propensity score matching was used to create a 1:1 cohort of patients
      managed by physicians or clinical pharmacy specialists. Patients were evaluated
      as their own control and as compared cohorts. The primary outcome was the
      difference in HbA1c. Secondary outcomes included changes in total cholesterol,
      low-density lipoprotein cholesterol, triglycerides, and body mass index. RESULTS:
      Data were collected from 124 patients (n = 62 CPS patients, n = 62 PCP patients).
      Baseline HbA1c in the CPS and PCP groups were 10.2% +/- 1.9% and 9.6% +/- 1.6%,
      respectively. Postintervention HbA1c in the CPS cohort was 7.5% +/- 1.1% (range,
      6-11.7%), indicating an absolute reduction of 2.7% (p < 0.001). Postintervention
      HbA1c in the PCP cohort was 8.5% +/- 1.5% (range, 5.4-12.6%), resulting in an
      absolute reduction of 1.1% (p < 0.001). The CPS intervention resulted in a
      greater mean HbA1c absolute reduction of 1.6 percentage points compared to
      physician intervention (p < 0.001). CONCLUSION: Compared with physician
      intervention, clinical pharmacy intervention in the treatment of T2D led to a
      greater mean HbA1c reduction in patients receiving care through VA facilities in
      rural settings.

PMID- 29472276
TI  - Using lean methodology to optimize time to antibiotic administration in patients
      with sepsis.
AB  - PURPOSE: Results of a study to apply lean methodology to an inpatient pharmacy
      workflow to optimize timely administration of Centers for Medicare and Medicaid
      Services (CMS)-approved antibiotics for patients with severe sepsis or septic
      shock are presented. METHODS: This quasi-experimental study was conducted at an
      802-bed institution using lean methodology to assess the inpatient pharmacy
      workflow for dispensing antibiotics to adult patients. The preintervention and
      postintervention phases occurred from February to September, 2015, and from
      October 2015 to May 2016, respectively. Patients were included if they were
      hospitalized with an intensive care department 9 or 10 code for severe sepsis or
      septic shock, had an order for a CMS-approved antibiotic, and met clinical
      criteria for severe sepsis or septic shock. Patients were excluded if they
      received first-dose antibiotics in the emergency department. The primary outcome
      was time from CMS-approved antibiotic order entry to medication administration.
      Secondary outcomes included timeliness of individual workflow dispensing
      parameters, patient outcomes, and compliance with the newly implemented workflow.
      RESULTS: A total of 102 patients were included, 54 in the preintervention and 48
      in the postintervention group. Baseline demographics between the groups were
      similar. There was a significant reduction in the median time from order entry to
      antibiotic administration by 40 minutes (preintervention phase 120 minutes versus
      postintervention phase 80 minutes, p = 0.014). Time from order verification to
      administration was significantly reduced. There was no difference in other
      secondary outcomes. CONCLUSION: Lean methodology was successfully used to reduce
      time to antibiotic administration, which led to improved compliance with the
      newly implemented sepsis CMS core measure.

PMID- 29472277
TI  - Documenting Stage 1 and 2 Meaningful Use criteria: A comparison of clinical
      pharmacists with other healthcare providers.
AB  - PURPOSE: Documentation of Stage 1 and Stage 2 Meaningful Use (MU) criteria for
      patients with type 2 diabetes mellitus between clinical pharmacists and other
      healthcare providers was compared. METHODS: Patients seen at 8 clinics in a
      federally qualified health center who had type 2 diabetes mellitus and were seen
      by clinical pharmacists or other healthcare providers were randomly selected for
      inclusion in this retrospective study. Approximately half of the encounters were
      evaluated for Stage 1 MU compliance (encounters from October through December
      2014), and half were evaluated for Stage 2 MU compliance (encounters from January
      through March 2015). Categorical and descriptive variables were analyzed by
      calculating frequencies and percentages. Chi-square tests were used to compare
      groups with an a priori level of significance set at 0.05. RESULTS: A total of
      790 patients were seen by 46 providers, 8 (18%) of whom were clinical
      pharmacists. The study also included 24 medical doctors, 8 family nurse
      practitioners, 1 physician assistant, and 5 doctors of osteopathic medicine.
      Other healthcare providers more consistently documented 5 Stage 1 MU criteria
      than did clinical pharmacists. Clinical pharmacists more consistently documented
      2 core objectives than did other healthcare providers. Otherwise, no significant
      differences in documentation were detected. CONCLUSION: Other healthcare
      providers more consistently documented 5 Stage 1 MU criteria than did clinical
      pharmacists. Clinical pharmacists more consistently documented 2 core objectives
      than did other healthcare providers.

PMID- 29472279
TI  - Comprehensive analysis of the MLH1 promoter region in 480 patients with
      colorectal cancer and 1150 controls reveals new variants including one with a
      heritable constitutional MLH1 epimutation.
AB  - BACKGROUND: Germline defects in MLH1, MSH2, MSH6 and PMS2 predisposing for Lynch
      syndrome (LS) are mainly based on sequence changes, whereas a constitutional
      epimutation of MLH1(CEM) is exceptionally rare. This abnormal MLH1 promoter
      methylation is not hereditary when arising de novo, whereas a stably heritable
      and variant-induced CEM was described for one single allele. We searched for MLH1
      promoter variants causing a germline or somatic methylation induction or
      transcriptional repression. METHODS: We analysed the MLH1 promoter sequence in
      five different patient groups with colorectal cancer (CRC) (n=480) composed of
      patients with i) CEM (n=16), ii) unsolved loss of MLH1 expression in CRC (n=37),
      iii) CpG-island methylator-phenotype CRC (n=102), iv) patients with LS (n=83) and
      v) MLH1-proficient CRC (n=242) as controls. 1150 patients with non-LS tumours
      also served as controls to correctly judge the results. RESULTS: We detected 10
      rare MLH1 promoter variants. One novel, complex MLH1 variant c.-63_-58delins18 is
      present in a patient with CRC with CEM and his sister, both showing a complete
      allele-specific promoter methylation and transcriptional silencing. The other
      nine promoter variants detected in 17 individuals were not associated with
      methylation. For four of these, a normal, biallelic MLH1 expression was found in
      the patients' cDNA. CONCLUSION: We report the second promoter variant stably
      inducing a hereditary CEM. Concerning the classification of promoter variants, we
      discuss contradictory results from the literature for two variants, describe
      classification discrepancies between existing rules for five variants, suggest
      the (re-)classification of five promoter variants to (likely) benign and regard
      four variants as functionally unclear.

PMID- 29472280
TI  - Letter by Guo et al Regarding Article, "Prevalence and Natural History of
      Superficial Siderosis: A Population-Based Study".

PMID- 29472281
TI  - Letter by Ellis and Sheets Regarding Article, "No Racial Difference in
      Rehabilitation Therapy Across All Post-Acute Care Settings in the Year Following
      a Stroke".

PMID- 29472278
TI  - SIAMESE-RELATED1 Is Regulated Posttranslationally and Participates in Repression
      of Leaf Growth under Moderate Drought.
AB  - The plant cell cycle is tightly regulated by factors that integrate endogenous
      cues and environmental signals to adapt plant growth to changing conditions.
      Under drought, cell division in young leaves is blocked by an active mechanism,
      reducing the evaporative surface and conserving energy resources. The molecular
      function of cyclin-dependent kinase-inhibitory proteins (CKIs) in regulating the
      cell cycle has already been well studied, but little is known about their
      involvement in cell cycle regulation under adverse growth conditions. In this
      study, we show that the transcript of the CKI gene SIAMESE-RELATED1 (SMR1) is
      quickly induced under moderate drought in young Arabidopsis (Arabidopsis
      thaliana) leaves. Functional characterization further revealed that SMR1 inhibits
      cell division and affects meristem activity, thereby restricting the growth of
      leaves and roots. Moreover, we demonstrate that SMR1 is a short-lived protein
      that is degraded by the 26S proteasome after being ubiquitinated by a Cullin-RING
      E3 ubiquitin ligase. Consequently, overexpression of a more stable variant of the
      SMR1 protein leads to a much stronger phenotype than overexpression of the native
      SMR1. Under moderate drought, both the SMR1 transcript and SMR1 protein
      accumulate. Despite this induction, smr1 mutants do not show overall tolerance to
      drought stress but do show less growth inhibition of young leaves under drought.
      Surprisingly, the growth-repressive hormone ethylene promotes SMR1 induction, but
      the classical drought hormone abscisic acid does not.

PMID- 29472282
TI  - Letter by Wolters Regarding Article, "Impact on Prehospital Delay of a Stroke
      Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster Randomized Controlled
      Trial)".

PMID- 29472283
TI  - Response by Denti and Schulz to Letter Regarding Article, "Impact on Prehospital
      Delay of a Stroke Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster
      Randomized Controlled Trial)".

PMID- 29472285
TI  - Seven days in medicine: 14-20 February 2018.

PMID- 29472284
TI  - Symbiosis in the microbial world: from ecology to genome evolution.
AB  - The concept of symbiosis - defined in 1879 by de Bary as 'the living together of
      unlike organisms' - has a rich and convoluted history in biology. In part,
      because it questioned the concept of the individual, symbiosis fell largely
      outside mainstream science and has traditionally received less attention than
      other research disciplines. This is gradually changing. In nature organisms do
      not live in isolation but rather interact with, and are impacted by, diverse
      beings throughout their life histories. Symbiosis is now recognized as a central
      driver of evolution across the entire tree of life, including, for example,
      bacterial endosymbionts that provide insects with vital nutrients and the
      mitochondria that power our own cells. Symbioses between microbes and their
      multicellular hosts also underpin the ecological success of some of the most
      productive ecosystems on the planet, including hydrothermal vents and coral
      reefs. In November 2017, scientists working in fields spanning the life sciences
      came together at a Company of Biologists' workshop to discuss the origin,
      maintenance, and long-term implications of symbiosis from the complementary
      perspectives of cell biology, ecology, evolution and genomics, taking into
      account both model and non-model organisms. Here, we provide a brief synthesis of
      the fruitful discussions that transpired.

PMID- 29472286
TI  - A novel de novo CAPN5 mutation in a patient with inflammatory vitreoretinopathy,
      hearing loss, and developmental delay.
AB  - Mutations that activate the protease calpain-5 (CAPN5) cause a nonsyndromic adult
      onset autoinflammatory eye disease characterized by uveitis, altered synaptic
      signaling, retinal degeneration, neovascularization, and intraocular fibrosis. We
      describe a pediatric patient with severe inflammatory vitreoretinopathy
      accompanied by hearing loss and developmental delay associated with a novel, de
      novo CAPN5 missense mutation (c.865C>T, p.Arg289Trp) that shows greater
      hyperactivation of the calpain protease, indicating a genotype-phenotype
      correlation that links mutation severity to proteolytic activity and the
      possibility of earlier onset syndromic disease with auditory and neurological
      abnormalities.

PMID- 29472289
TI  - Preventing disease by integrating physical activity in clinical practice: what
      works for whom?

PMID- 29472288
TI  - Usefulness of positron emission tomography/computed tomography in patients with
      valve-tube graft infection.
AB  - OBJECTIVE: Infection of valved aortic grafts is a rare entity whose diagnosis
      remains challenging. Positron emission tomography (PET)/CT has become a criterion
      for the diagnosis of infective endocarditis (IE) in prosthetic valves, but its
      role on ascending aortic graft infections remains unclear. This study aims to
      assess the diagnostic value of PET/CT in patients with valved aortic graft
      infection. METHODS: 12 episodes with a valved aortic graft who had undergone a
      PET/CT due to suspicion of IE were prospectively included (group I) and compared
      with five controls free of infection who underwent PET/CT for other reasons
      (group II). Pathological uptake of 18F-fluorodeoxyglucose (FDG) and its pattern
      at the prosthetic valve and aortic graft were studied. RESULTS: Diagnosis of IE
      was confirmed in 9 out of 12 episodes of group I. 18F-FDG uptake was detectable
      in eight out of nine cases with a final diagnosis of IE. The most repeated
      pattern of uptake was homogeneous around the valve and heterogeneous around the
      tube. There was one false-negative study. Of the three patients in which IE was
      ruled out, there were two false positives and one true negative. In group II,
      there were three patients with a positive PET/CT study, two of them had active
      aortitis and the third was considered false positive. CONCLUSIONS: 18F-FDG PET/CT
      shows high sensitivity in the detection of infected aortic grafts. Thus, this
      technique should be considered in the diagnostic work-up of patients with
      suspicion of aortic graft infection. However, further validation of this approach
      is needed.

PMID- 29472290
TI  - Coronary heart disease risk associated with the dyslipidaemia of chronic kidney
      disease.
AB  - OBJECTIVE: This study sought to characterise the main dyslipidaemic phenotypes
      present in chronic kidney disease (CKD) and their association with coronary heart
      disease (CHD) risk. METHODS: Analyses included 6612 individuals in the
      multiethnic study of atherosclerosis free of CHD at baseline. CKD was defined as
      an estimated glomerular filtration rate (eGFR) of 15 to <60 mL/min/1.73 m2
      (stages 3-4). Principal component analyses were used to characterise the main
      dyslipidaemic phenotypes of CKD accounting for the correlation among different
      lipoproteins and lipoprotein particles. CHD was defined as incident myocardial
      infarction, angina followed by revascularisation, resuscitated cardiac arrest or
      CHD death. RESULTS: CHD developed in 303 individuals (5%) with eGFR >=60 and in
      72 individuals (12%) with CKD (p for difference <0.001). A dyslipidaemic
      phenotype (principal component 1 (PC1)) consisting of elevations in
      triglycerides, triglyceride-rich lipoproteins (VLDL particles), small LDL
      particles and reductions in HDL particles, was more common in those with CKD,
      compared with those without CKD (p for difference <0.001). This phenotype was
      also more strongly associated with CHD in those with CKD: adjusted HRs (95% CIs)
      per SD increase in PC1 1.13 (95% CI 1.00 to 1.27; P=0.05) and 1.51 (95% CI 1.17
      to 1.94; P<0.001) in eGFR >=60 and CKD, respectively (P for interaction=0.05).
      CONCLUSION: In individuals with mainly stage 3 CKD, a dominant lipid phenotype
      consisting of triglyceride-rich lipoproteins and other closely correlated
      lipoproteins is strongly associated with CHD risk. Future studies should
      investigate whether modification of the components of this phenotype leads to a
      reduction in the CHD burden in individuals with CKD.

PMID- 29472292
TI  - Repair of partial atrioventricular septal defects in infancy: a paradigm shift or
      a road block?

PMID- 29472291
TI  - Outcomes after surgical coronary artery revascularisation in children with
      congenital heart disease.
AB  - OBJECTIVE: Surgical coronary revascularisation in children with congenital heart
      disease (CHD) is a rare event for which limited information is available. In this
      study, we review the indications and outcomes of surgical coronary
      revascularisation from the Pediatric Cardiac Care Consortium, a large US-based
      multicentre registry of interventions for CHD. METHODS: This is a retrospective
      cohort study of children (<18 years old) with CHD who underwent surgical coronary
      revascularisation between 1982 and 2011. In-hospital mortality and graft patency
      data were obtained from the registry. Long-term transplant-free survival through
      2014 was achieved for patients with adequate identifiers via linkage with the US
      National Death Index and the Organ Procurement and Transplantation Network.
      RESULTS: Coronary revascularisation was accomplished by bypass grafting (n=72,
      median age 6.8 years, range 3 days-17.4 years) or other operations (n=65, median
      age 2.6 years, range 5 days-16.7 years) in 137 patients. Most revascularisations
      were related to the aortic root (61.3%) or coronary anomalies (27.7%), but 10.9%
      of them were unrelated to either of them. Twenty in-hospital deaths occurred, 70%
      of them after urgent 'rescue' revascularisation in association with another
      operation. Long-term outcomes were available by external linkage for 54 patients
      surviving to hospital discharge (median follow-up time 15.0 years, max follow-up
      29.8 years) with a 15-year transplant-free survival of 91% (95% CI 83% to 99%).
      CONCLUSIONS: Surgical coronary revascularisation can be performed in children
      with CHD with acceptable immediate and long-term survival. Outcomes are dependent
      on indication, with the highest mortality in rescue procedures.

PMID- 29472293
TI  - Degradation of the endoplasmic reticulum-anchored transcription factor MyRF by
      the ubiquitin ligase SCFFbxw7 in a manner dependent on the kinase GSK-3.
AB  - The ubiquitin-proteasome system regulates the abundance of many cellular proteins
      by mediating their targeted degradation. We previously developed a method
      differential proteomics-based identification of ubiquitylation substrates
      (DiPIUS)-for the comprehensive identification of substrates for a given F-box
      protein subunit of SCF-type ubiquitin ligases. We have now applied DiPIUS to the
      F-box protein Fbxw7 in three cell lines (mHepa, Neuro2A, and C2C12) and thereby
      identified myelin regulatory factor (MyRF), an endoplasmic reticulum-anchored
      transcription factor that is essential for myelination of nerves in the central
      nervous system, as a candidate substrate of Fbxw7 specifically in mHepa cells. Co
      immunoprecipitation analysis confirmed that the NH2-terminal cytoplasmic domain
      of MyRF interacted with Fbxw7 in these cells. Furthermore, an in vitro
      ubiquitylation assay revealed that MyRF undergoes polyubiquitylation in the
      presence of purified recombinant SCFFbxw7 In addition, the stability of MyRF in
      mHepa cells was increased by mutation of a putative phosphodegron sequence or by
      exposure of the cells to an inhibitor of glycogen synthase kinase-3 (GSK-3). We
      found that MyRF mRNA is not restricted to the central nervous system but is
      instead distributed widely among mouse tissues. Furthermore, with the use of RNA
      sequencing in mHepa cells overexpressing or depleted of MyRF, we identified many
      novel potential target genes of MyRF. Our results thus suggest that Fbxw7
      controls the transcription of MyRF target genes in various tissues through
      regulation of MyRF protein stability in a manner dependent on MyRF
      phosphorylation by GSK-3.

PMID- 29472295
TI  - Association between proton pump inhibitors use and risk of gastric cancer in
      patients with GERD.

PMID- 29472294
TI  - Impact of the epoxide hydrolase EphD on the metabolism of mycolic acids in
      mycobacteria.
AB  - Mycolic acids are the hallmark of the cell envelope in mycobacteria, which
      include the important human pathogens Mycobacterium tuberculosis and
      Mycobacterium leprae Mycolic acids are very long C60-C90 alpha-alkyl beta-hydroxy
      fatty acids having a variety of functional groups on their hydrocarbon chain that
      define several mycolate types. Mycobacteria also produce an unusually large
      number of putative epoxide hydrolases, but the physiological functions of these
      enzymes are still unclear. Here, we report that the mycobacterial epoxide
      hydrolase EphD is involved in mycolic acid metabolism. We found that orthologs of
      EphD from M. tuberculosis and M. smegmatis are functional epoxide hydrolases,
      cleaving a lipophilic substrate, 9,10-cis-epoxystearic acid, in vitro and forming
      a vicinal diol. The results of EphD overproduction in M. smegmatis and M. bovis
      BCG Deltahma strains producing epoxymycolic acids indicated that EphD is involved
      in the metabolism of these forms of mycolates in both fast- and slow-growing
      mycobacteria. Moreover, using MALDI-TOF-MS and 1H NMR spectroscopy of mycolic
      acids and lipids isolated from EphD-overproducing M. smegmatis, we identified new
      oxygenated mycolic acid species that accumulated during epoxymycolate depletion.
      Disruption of the ephD gene in M. tuberculosis specifically impaired the
      synthesis of ketomycolates and caused accumulation of their precursor,
      hydroxymycolate, indicating either direct or indirect involvement of EphD in
      ketomycolate biosynthesis. Our results clearly indicate that EphD plays a role in
      metabolism of oxygenated mycolic acids in mycobacteria.

PMID- 29472297
TI  - Intraoperative Conebeam CT for Assessment of Intracochlear Positioning of
      Electrode Arrays in Adult Recipients of Cochlear Implants.
AB  - BACKGROUND AND PURPOSE: Intraoperative conebeam CT has been introduced into the
      operating room and provides quick radiologic feedback. This study aimed to
      investigate its utility in the assessment of the positioning of the electrode
      array after cochlear implantation. MATERIALS AND METHODS: This was a
      retrospective study of 51 patients (65 ears) with intraoperative imaging by
      conebeam CT (O-arm) after cochlear implantation between 2013 and 2017. Correct
      placement into the cochlea was immediately identified. Positioning assessments
      were later analyzed with OsiriX software. RESULTS: Intraoperative imaging was
      quickly performed in all cases. No misplacement into the vestibule or
      semicircular canals was found. A foldover of the implanted array was identified
      in 1 patient. Secondary analysis by 2 raters showed excellent agreement on
      insertion depth angle (intraclass correlation = 0.96, P < .001) and length of
      insertion of the electrode array (intraclass correlation coefficient = 0.93, P =
      .04) measurements. The evaluation of the number of extracochlear electrodes was
      identical between the 2 raters in 78% of cases (Cohen kappa = 0.55, P < .001).
      The scalar position was inconsistent between raters. When we compared O-arm and
      high-resolution CT images in 14 cases, the agreement was excellent for insertion
      depth angle (intraclass correlation coefficient = 0.97, P < .001) and insertion
      length (intraclass correlation coefficient = 0.98, P < .001), good for the number
      of extracochlear electrodes (Cohen kappa = 0.63, P = .01), but moderate for the
      scalar position (Cohen kappa = 0.59, P = .02). CONCLUSIONS: Intraoperative
      conebeam CT using the O-arm is a safe, rapid, easy, and reliable procedure to
      immediately identify a misplacement or foldover of an electrode array. The
      insertion depth angle, insertion length, and number of electrodes inserted can be
      accurately assessed.

PMID- 29472296
TI  - Brain Injury Lesion Imaging Using Preconditioned Quantitative Susceptibility
      Mapping without Skull Stripping.
AB  - BACKGROUND AND PURPOSE: Identifying cerebral microhemorrhage burden can aid in
      the diagnosis and management of traumatic brain injury, stroke, hypertension, and
      cerebral amyloid angiopathy. MR imaging susceptibility-based methods are more
      sensitive than CT for detecting cerebral microhemorrhage, but methods other than
      quantitative susceptibility mapping provide results that vary with field strength
      and TE, require additional phase maps to distinguish blood from calcification,
      and depict cerebral microhemorrhages as bloom artifacts. Quantitative
      susceptibility mapping provides universal quantification of tissue magnetic
      property without these constraints but traditionally requires a mask generated by
      skull-stripping, which can pose challenges at tissue interphases. We evaluated
      the preconditioned quantitative susceptibility mapping MR imaging method, which
      does not require skull-stripping, for improved depiction of brain parenchyma and
      pathology. MATERIALS AND METHODS: Fifty-six subjects underwent brain MR imaging
      with a 3D multiecho gradient recalled echo acquisition. Mask-based quantitative
      susceptibility mapping images were created using a commonly used mask-based
      quantitative susceptibility mapping method, and preconditioned quantitative
      susceptibility images were made using precondition-based total field inversion.
      All images were reviewed by a neuroradiologist and a radiology resident. RESULTS:
      Ten subjects (18%), all with traumatic brain injury, demonstrated blood products
      on 3D gradient recalled echo imaging. All lesions were visible on preconditioned
      quantitative susceptibility mapping, while 6 were not visible on mask-based
      quantitative susceptibility mapping. Thirty-one subjects (55%) demonstrated brain
      parenchyma and/or lesions that were visible on preconditioned quantitative
      susceptibility mapping but not on mask-based quantitative susceptibility mapping.
      Six subjects (11%) demonstrated pons artifacts on preconditioned quantitative
      susceptibility mapping and mask-based quantitative susceptibility mapping; they
      were worse on preconditioned quantitative susceptibility mapping. CONCLUSIONS:
      Preconditioned quantitative susceptibility mapping MR imaging can bring the
      benefits of quantitative susceptibility mapping imaging to clinical practice
      without the limitations of mask-based quantitative susceptibility mapping,
      especially for evaluating cerebral microhemorrhage-associated pathologies, such
      as traumatic brain injury.

PMID- 29472298
TI  - Sonographic Development of the Pericallosal Vascularization in the First and
      Early Second Trimester of Pregnancy.
AB  - BACKGROUND AND PURPOSE: Anomalies of the corpus callosum are rare. Routine
      scanning in midtrimester of the pregnancy often fails to identify defective
      development. The purpose of the study was to identify the pericallosal artery and
      all its main branching arteries during early gestation from the first trimester
      onward, to measure the length of the pericallosal artery during its development,
      and to establish a normal vascular map for each week of development. MATERIALS
      AND METHODS: We performed a single-center prospective, longitudinal clinical
      study in 15 patients between 11 and 22 weeks of gestation. The origin and course
      of the different blood vessels were identified. RESULTS: There was a linear
      association among gestational age, the biparietal diameter, and the length of the
      pericallosal artery. The curvature of the developing pericallosal artery
      increases linearly with the gestational age and biparietal diameter, and 4
      variations of branching of the callosomarginal artery were observed. CONCLUSIONS:
      The pericallosal artery and its branches can be identified and measured from 11
      weeks on, and the pericallosal artery takes its characteristic course. A
      defective course or an abnormal biometry of the pericallosal artery could be an
      early sonographic marker of abnormal development of the corpus callosum.

PMID- 29472299
TI  - Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI
      for Multiple Sclerosis.
AB  - BACKGROUND AND PURPOSE: Inhomogeneous magnetization transfer is a new endogenous
      MR imaging contrast mechanism that has demonstrated high specificity for myelin.
      Here, we tested the hypothesis that inhomogeneous magnetization transfer is
      sensitive to pathology in a population of patients with relapsing-remitting MS in
      a way that both differs from and complements conventional magnetization transfer.
      MATERIALS AND METHODS: Twenty-five patients with relapsing-remitting MS and 20
      healthy volunteers were enrolled in a prospective MR imaging research study,
      whose protocol included anatomic imaging, standard magnetization transfer, and
      inhomogeneous magnetization transfer imaging. Magnetization transfer and
      inhomogeneous magnetization transfer ratios measured in normal-appearing brain
      tissue and in MS lesions of patients were compared with values measured in
      control subjects. The potential association of inhomogeneous magnetization
      transfer ratio variations with the clinical scores (Expanded Disability Status
      Scale) of patients was further evaluated. RESULTS: The magnetization transfer
      ratio and inhomogeneous magnetization transfer ratio measured in the thalami and
      frontal, occipital, and temporal WM of patients with MS were lower compared with
      those of controls (P < .05). The mean inhomogeneous magnetization transfer ratio
      measured in lesions was lower than that in normal-appearing WM (P < .05).
      Significant (P < .05) negative correlations were found between the clinical
      scores and inhomogeneous magnetization transfer ratio measured in normal
      appearing WM structures. Weaker nonsignificant correlation trends were found for
      the magnetization transfer ratio. CONCLUSIONS: The sensitivity of the
      inhomogeneous magnetization transfer technique for MS was highlighted by the
      reduction in the inhomogeneous magnetization transfer ratio in MS lesions and in
      normal-appearing WM of patients compared with controls. Stronger correlations
      with the Expanded Disability Status Scale score were obtained with the
      inhomogeneous magnetization transfer ratio compared with the standard
      magnetization transfer ratio, which may be explained by the higher specificity of
      inhomogeneous magnetization transfer for myelin.

PMID- 29472301
TI  - Revenue Increase following 2017 Multiple Procedures Payment Reduction
      Modification: Differential Impact on Neuroradiology-Report from an Academic
      Medical Center.
AB  - BACKGROUND AND PURPOSE: The Centers for Medicare and Medicaid Services imposed a
      25% professional component multiple procedure payment reduction for the
      professional component of advanced diagnostic imaging modalities in January 2012.
      In 2017, the Centers for Medicare and Medicaid Services rolled back the multiple
      procedure payment reduction to 5% for subsequent imaging. To evaluate the effect
      of this change, we analyzed 5 months of Centers for Medicare and Medicaid
      Services procedures at Johns Hopkins Medical Institution. MATERIALS AND METHODS:
      We analyzed the procedure codes and reimbursement rate for studies performed
      between January 1 and May 31, 2017. Patients with Medicare insurance who had
      multiple diagnostic procedures in a day were selected. Per the Centers for
      Medicare and Medicaid Services guidelines, procedures with the highest price were
      considered fully reimbursed and subsequent studies were marked for differences
      between 25% (2013-2016) and 5% reduction (2017). RESULTS: We included 8787
      patients with 22,236 procedures (mean, 2.53 studies/day). CT, MR imaging, and
      ultrasound scans composed 75.9%, 21.5%, and 2.6% of all studies, with 61.2%,
      54.9%, and 85.4% of the procedures of each technique subject to multiple
      procedure payment reduction, respectively. The projected reimbursement for these
      studies was $1,666,437, which translated to a $179,782 (12.1%) increase in
      revenue comparing 25%-versus-5% multiple procedure payment reduction rates for 5
      months: $128,542 for CT, $47,802 for MR imaging, and $3439 for ultrasound. The
      annual overall prorated increase in revenue would be $431,476. The impact was
      maximal for neuroradiology. CONCLUSIONS: With the recent favorable adjustment in
      multiple procedure payment reduction regulations, CT-heavy subspecialties like
      neuroradiology benefit the most with revenue increases. Different practice
      settings might experience revenue increases to a different extent, depending on
      the procedure and payer mix.

PMID- 29472300
TI  - An Automated Statistical Technique for Counting Distinct Multiple Sclerosis
      Lesions.
AB  - BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis,
      yet it has historically shown modest association with clinical outcome. Lesion
      count, which encapsulates the natural history of lesion formation and is thought
      to provide complementary information, is difficult to assess in patients with
      confluent (ie, spatially overlapping) lesions. We introduce a statistical
      technique for cross-sectionally counting pathologically distinct lesions.
      MATERIALS AND METHODS: MR imaging was used to assess the probability of a lesion
      at each location. The texture of this map was quantified using a novel technique,
      and clusters resembling the center of a lesion were counted. Validity compared
      with a criterion standard count was demonstrated in 60 subjects observed
      longitudinally, and reliability was determined using 14 scans of a clinically
      stable subject acquired at 7 sites. RESULTS: The proposed count and the criterion
      standard count were highly correlated (r = 0.97, P < .001) and not significantly
      different (t59 = -.83, P = .41), and the variability of the proposed count across
      repeat scans was equivalent to that of lesion load. After accounting for lesion
      load and age, lesion count was negatively associated (t58 = -2.73, P < .01) with
      the Expanded Disability Status Scale. Average lesion size had a higher
      association with the Expanded Disability Status Scale (r = 0.35, P < .01) than
      lesion load (r = 0.10, P = .44) or lesion count (r = -.12, P = .36) alone.
      CONCLUSIONS: This study introduces a novel technique for counting pathologically
      distinct lesions using cross-sectional data and demonstrates its ability to
      recover obscured longitudinal information. The proposed count allows more
      accurate estimation of lesion size, which correlated more closely with disability
      scores than either lesion load or lesion count alone.

PMID- 29472302
TI  - Quantification of Intracranial Aneurysm Volume Pulsation with 7T MRI.
AB  - BACKGROUND AND PURPOSE: Aneurysm volume pulsation is a potential predictor of
      intracranial aneurysm rupture. We evaluated whether 7T MR imaging can quantify
      aneurysm volume pulsation. MATERIALS AND METHODS: In Stage I of the study, 10
      unruptured aneurysms in 9 patients were studied using a high-resolution (0.6-mm,
      isotropic) 3D gradient-echo sequence with cardiac gating. Semiautomatic
      segmentation was used to measure aneurysm volume (in cubic millimeters) per
      cardiac phase. Aneurysm pulsation was defined as the relative increase in volume
      between the phase with the smallest volume and the phase with the largest volume.
      The accuracy and precision of the measured volume pulsations were addressed by
      digital phantom simulations and a repeat image analysis. In Stage II, the imaging
      protocol was optimized and 9 patients with 9 aneurysms were studied with and
      without administration of a contrast agent. RESULTS: The mean aneurysm pulsation
      in Stage I was 8% +/- 7% (range, 2%-27%), with a mean volume change of 15 +/- 14
      mm3 (range, 3-51 mm3). The mean difference in volume change for the repeat image
      analysis was 2 +/- 6 mm3. The artifactual volume pulsations measured with the
      digital phantom simulations were of the same magnitude as the volume pulsations
      observed in the patient data, even after protocol optimization in Stage II.
      CONCLUSIONS: Volume pulsation quantification with the current imaging protocol on
      7T MR imaging is not accurate due to multiple imaging artifacts. Future studies
      should always include aneurysm-specific accuracy analysis.

PMID- 29472303
TI  - HARMless: Transient Cortical and Sulcal Hyperintensity on Gadolinium-Enhanced
      FLAIR after Elective Endovascular Coiling of Intracranial Aneurysms.
AB  - BACKGROUND AND PURPOSE: Cortical and sulcal hyperintensity on gadolinium-enhanced
      FLAIR has been increasingly recognized after iodinated contrast medium exposure
      during angiographic procedures. The goal of this study was to assess the
      relationship of cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR
      against various variables in patients following elective endovascular treatment
      of intracranial aneurysms. MATERIALS AND METHODS: We performed a retrospective
      review of 58 patients with 62 MR imaging studies performed within 72 hours
      following endovascular treatment of intracranial aneurysms. Patient demographics,
      aneurysm location, and vascular territory distribution of cortical and sulcal
      hyperintensity on gadolinium-enhanced FLAIR were documented. Analysis of cortical
      and sulcal hyperintensity on gadolinium-enhanced FLAIR with iodinated contrast
      medium volume, procedural duration, number of angiographic runs, and DWI lesions
      was performed. RESULTS: Cortical and sulcal hyperintensity on gadolinium-enhanced
      FLAIR was found in 32/62 (51.61%) post-endovascular treatment MR imaging studies,
      with complete resolution of findings in all patients on the available follow-up
      studies (27/27). Angiographic iodinated contrast medium injection and arterial
      anatomy matched the vascular distribution of cortical and sulcal hyperintensity
      on gadolinium-enhanced FLAIR. No significant association was found between
      cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR with iodinated
      contrast medium volume (P = .56 value) and the presence of DWI lesions (P = .68).
      However, a significant association was found with procedural time (P = .001) and
      the number of angiographic runs (P = .019). No adverse clinical outcomes were
      documented. CONCLUSIONS: Cortical and sulcal hyperintensity on gadolinium
      enhanced FLAIR is a transient observation in the arterial territory exposed to
      iodinated contrast medium during endovascular treatment of intracranial
      aneurysms. Cortical and sulcal hyperintensity on gadolinium-enhanced FLAIR is
      significantly associated with procedural time, and the frequency of angiographic
      runs suggesting a potential technical influence on the breakdown of the BBB, but
      no reported adverse clinical outcome or association with both iodinated contrast
      medium volume and DWI lesions was found. Recognition of cortical and sulcal
      hyperintensity on gadolinium-enhanced FLAIR as a benign incidental finding is
      vital to avoid unnecessary investigation.

PMID- 29472304
TI  - Responsive Designed Interventions Are Needed to Support Positive Outcomes of
      Children and Adolescents with CKD.

PMID- 29472305
TI  - Metabolic and Hypertensive Complications of Pregnancy in Women with
      Nephrolithiasis.
AB  - BACKGROUND AND OBJECTIVES: Kidney stones are associated with future development
      of hypertension, diabetes, and the metabolic syndrome. Our objective was to
      assess whether stone formation before pregnancy was associated with metabolic and
      hypertensive complications in pregnancy. We hypothesized that stone formation is
      a marker of metabolic disease and would be associated with higher risk for
      maternal complications in pregnancy. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We conducted a retrospective cohort study of women who delivered
      infants at the Massachusetts General Hospital from 2006 to 2015. Women with
      abdominal imaging (computed tomography or ultrasound) before pregnancy were
      included in the analysis. Pregnancy outcomes in women with documented kidney
      stones on imaging (stone formers, n=166) were compared with those of women
      without stones on imaging (controls, n=1264). Women with preexisting CKD,
      hypertension, and diabetes were excluded. RESULTS: Gestational diabetes and
      preeclampsia were more common in stone formers than nonstone formers (18% versus
      6%, respectively; P<0.001 and 16% versus 8%, respectively; P=0.002). After
      multivariable adjustment, previous nephrolithiasis was associated with higher
      risks of gestational diabetes (adjusted odds ratio, 3.1; 95% confidence interval,
      1.8 to 5.3) and preeclampsia (adjusted odds ratio, 2.2; 95% confidence interval,
      1.3 to 3.6). Infants of stone formers were born earlier (38.7+/-2.0 versus 39.2+/
      1.7 weeks, respectively; P=0.01); however, rates of small for gestational age
      offspring and neonatal intensive care admission were similar between groups (8%
      versus 7%, respectively; P=0.33 and 10% versus 6%, respectively; P=0.08). First
      trimester body mass index significantly influenced the association between stone
      disease and hypertensive complications of pregnancy: in a multivariable linear
      regression model, stone formation acted as an effect modifier of the relationship
      between maximum systolic BP in the third trimester and body mass index (P
      interaction <0.001). CONCLUSIONS: In women without preexisting diabetes,
      hypertension, and CKD, a history of nephrolithiasis was associated with
      gestational diabetes and hypertensive disorders of pregnancy, especially in women
      with high first trimester body mass index.

PMID- 29472306
TI  - Neurocognitive and Educational Outcomes in Children and Adolescents with CKD: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND OBJECTIVES: Poor cognition can affect educational attainment, but
      the extent of neurocognitive impairment in children with CKD is not well
      understood. This systematic review assessed global and domain-specific cognition
      and academic skills in children with CKD and whether these outcomes varied with
      CKD stage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Electronic databases
      were searched for observational studies of children with CKD ages 21 years old or
      younger that assessed neurocognitive or educational outcomes. Risk of bias was
      assessed using a modified Newcastle-Ottawa scale. We used random effects models
      and expressed the estimates as mean differences with 95% confidence intervals
      stratified by CKD stage. RESULTS: Thirty-four studies (25 cross-sectional,
      n=2095; nine cohort, n=991) were included. The overall risk of bias was high
      because of selection and measurement biases. The global cognition (full-scale
      intelligence quotient) of children with CKD was classified as low average.
      Compared with the general population, the mean differences (95% confidence
      intervals) in full-scale intelligence quotient were -10.5 (95% confidence
      interval, -13.2 to -7.72; all CKD stages, n=758), -9.39 (95% confidence interval,
      -12.6 to -6.18; mild to moderate stage CKD, n=582), -16.2 (95% confidence
      interval, -33.2 to 0.86; dialysis, n=23), and -11.2 (95% confidence interval, 
      17.8 to -4.50; transplant, n=153). Direct comparisons showed that children with
      mild to moderate stage CKD and kidney transplants scored 11.2 (95% confidence
      interval, 2.98 to 19.4) and 10.1 (95% confidence interval, -1.81 to 22.0) full
      scale intelligence quotient points higher than children on dialysis. Children
      with CKD also had lower scores than the general population in executive function
      and memory (verbal and visual) domains. Compared with children without CKD, the
      mean differences in academic skills (n=518) ranged from -15.7 to -1.22 for
      mathematics, from -9.04 to -0.17 for reading, and from -14.2 to 2.53 for
      spelling. CONCLUSIONS: Children with CKD may have low-average cognition compared
      with the general population, with mild deficits observed across academic skills,
      executive function, and visual and verbal memory. Limited evidence suggests that
      children on dialysis may be at greatest risk compared with children with mild to
      moderate stage CKD and transplant recipients.

PMID- 29472307
TI  - A Genome-Wide Association Study for Host Resistance to Ostreid Herpesvirus in
      Pacific Oysters (Crassostrea gigas).
AB  - Ostreid herpesvirus (OsHV) can cause mass mortality events in Pacific oyster
      aquaculture. While various factors impact on the severity of outbreaks, it is
      clear that genetic resistance of the host is an important determinant of
      mortality levels. This raises the possibility of selective breeding strategies to
      improve the genetic resistance of farmed oyster stocks, thereby contributing to
      disease control. Traditional selective breeding can be augmented by use of
      genetic markers, either via marker-assisted or genomic selection. The aim of the
      current study was to investigate the genetic architecture of resistance to OsHV
      in Pacific oyster, to identify genomic regions containing putative resistance
      genes, and to inform the use of genomics to enhance efforts to breed for
      resistance. To achieve this, a population of ~1,000 juvenile oysters were
      experimentally challenged with a virulent form of OsHV, with samples taken from
      mortalities and survivors for genotyping and qPCR measurement of viral load. The
      samples were genotyped using a recently-developed SNP array, and the genotype
      data were used to reconstruct the pedigree. Using these pedigree and genotype
      data, the first high density linkage map was constructed for Pacific oyster,
      containing 20,353 SNPs mapped to the ten pairs of chromosomes. Genetic parameters
      for resistance to OsHV were estimated, indicating a significant but low
      heritability for the binary trait of survival and also for viral load measures
      (h2 0.12 - 0.25). A genome-wide association study highlighted a region of linkage
      group 6 containing a significant QTL affecting host resistance. These results are
      an important step toward identification of genes underlying resistance to OsHV in
      oyster, and a step toward applying genomic data to enhance selective breeding for
      disease resistance in oyster aquaculture.

PMID- 29472308
TI  - Systematic Complex Haploinsufficiency-Based Genetic Analysis of Candida albicans
      Transcription Factors: Tools and Applications to Virulence-Associated Phenotypes.
AB  - Genetic interaction analysis is a powerful approach to the study of complex
      biological processes that are dependent on multiple genes. Because of the largely
      diploid nature of the human fungal pathogen Candida albicans, genetic interaction
      analysis has been limited to a small number of large-scale screens and a handful
      for gene-by-gene studies. Complex haploinsufficiency, which occurs when a strain
      containing two heterozygous mutations at distinct loci shows a phenotype that is
      distinct from either of the corresponding single heterozygous mutants, is an
      expedient approach to genetic interactions analysis in diploid organisms. Here,
      we describe the construction of a barcoded-library of 133 heterozygous TF
      deletion mutants and deletion cassettes for designed to facilitate complex
      haploinsufficiency-based genetic interaction studies of the TF networks in C.
      albicans We have characterized the phenotypes of these heterozygous mutants under
      a broad range of in vitro conditions using both agar-plate and pooled signature
      tag-based assays. Consistent with previous studies, haploinsufficiency is
      relative uncommon. In contrast, a set of 12 TFs enriched in mutants with a role
      in adhesion were found to have altered competitive fitness at early time points
      in a murine model of disseminated candidiasis. Finally, we characterized the
      genetic interactions of a set of biofilm related TFs in the first two steps of
      biofilm formation, adherence and filamentation of adherent cells. The genetic
      interaction networks at each stage of biofilm formation are significantly
      different indicating that the network is not static but dynamic.

PMID- 29472309
TI  - Photosensitive Alternative Splicing of the Circadian Clock Gene timeless Is
      Population Specific in a Cold-Adapted Fly, Drosophila montana.
AB  - To function properly, organisms must adjust their physiology, behavior and
      metabolism in response to a suite of varying environmental conditions. One of the
      central regulators of these changes is organisms' internal circadian clock, and
      recent evidence has suggested that the clock genes are also important in the
      regulation of seasonal adjustments. In particular, thermosensitive splicing of
      the core clock gene timeless in a cosmopolitan fly, Drosophila melanogaster, has
      implicated this gene to be involved in thermal adaptation. To further investigate
      this link we examined the splicing of timeless in a northern malt fly species,
      Drosophila montana, which can withstand much colder climatic conditions than its
      southern relative. We studied northern and southern populations from two
      different continents (North America and Europe) to find out whether and how the
      splicing of this gene varies in response to different temperatures and day
      lengths. Interestingly, we found that the expression of timeless splice variants
      was sensitive to differences in light conditions, and while the flies of all
      study populations showed a change in the usage of splice variants in constant
      light compared to LD 22:2, the direction of the shift varied between populations.
      Overall, our findings suggest that the splicing of timeless in northern
      Drosophila montana flies is photosensitive, rather than thermosensitive and
      highlights the value of studying multiple species and populations in order to
      gain perspective on the generality of gene function changes in different kinds of
      environmental conditions.

PMID- 29472310
TI  - Temozolomide Plus Bevacizumab in Elderly Patients with Newly Diagnosed
      Glioblastoma and Poor Performance Status: An ANOCEF Phase II Trial (ATAG).
AB  - LESSONS LEARNED: Results suggest that the combination of bevacizumab plus
      temozolomide is active in terms of response rate, survival, performance, quality
      of life, and cognition in elderly patients with glioblastoma multiforme with poor
      performance status.Whether this combination is superior to temozolomide alone
      remains to be demonstrated by a randomized study. BACKGROUND: The optimal
      treatment of glioblastoma multiforme (GBM) in patients aged >=70 years with a
      Karnofsky performance status (KPS) <70 is not established. This clinical trial
      evaluated the efficacy and safety of upfront temozolomide (TMZ) and bevacizumab
      (Bev) in patients aged >=70 years and a KPS <70. MATERIALS AND METHODS: Patients
      aged >=70 years with a KPS <70 and biopsy-proven GBM were eligible for this
      multicenter, prospective, nonrandomized, phase II trial of older patients with
      impaired performance status. Treatment consisted of TMZ administered at 130-150
      mg/m2 per day for 5 days every 4 weeks plus Bev administered at 10 mg/kg every 2
      weeks. RESULTS: The trial included 66 patients (median age of 76 years; median
      KPS of 60). The median overall survival (OS) was 23.9 weeks (95% confidence
      interval [CI], 19-27.6), and the median progression-free survival (PFS) was 15.3
      weeks (95% CI, 12.9-19.3). Twenty-two (33%) patients became transiently capable
      of self-care (i.e., KPS >70). Cognition and quality of life significantly
      improved over time during treatment. Grade >=3 hematological adverse events
      occurred in 13 (20%) patients, high blood pressure in 16 (24%), venous
      thromboembolism in 3 (4.5%), cerebral hemorrhage in 2 (3%), and intestinal
      perforation in 2 (3%). CONCLUSION: This study suggests that TMZ + Bev treatment
      is active in elderly patients with GBM with low KPS and has an acceptable
      tolerance level.

PMID- 29472311
TI  - Cancer Diagnosis: A Trauma for Patients and Doctors Alike.

PMID- 29472312
TI  - Complete Remission Following Pembrolizumab in a Woman with Mismatch Repair
      Deficient Endometrial Cancer and a Germline BRCA1 Mutation.
AB  - : Endometrial cancer is the most common gynecologic malignancy in the U.S. and,
      although the majority of cases present at an early stage and can be treated with
      curative intent, those who present with advanced disease, or develop metastatic
      or recurrent disease, have a poorer prognosis. A subset of endometrial cancers
      exhibit mismatch repair (MMR) deficiency. It is now recognized that MMR-deficient
      cancers are particularly susceptible to programmed cell death protein 1 (PD
      1)/programmed death-ligand 1 (PD-L1) inhibitors, and in a landmark judgement in
      2017, the U.S. Food and Drug Administration granted accelerated approval to
      pembrolizumab for these tumors, the first tumor-agnostic approval of a drug.
      However, less is known about the sensitivity to PD-1 blockade among patients with
      known mutations in double-strand break DNA repair pathways involving homologous
      recombination, such as those in BRCA1 or BRCA2. Here we report a case of a
      patient with an aggressive somatic MMR-deficient endometrial cancer and a
      germline BRCA1 who experienced a rapid complete remission to pembrolizumab. KEY
      POINTS: Endometrial cancers, and in particular endometrioid carcinomas, should
      undergo immunohistochemical testing for mismatch repair proteins.Uterine cancers
      with documented mismatch repair deficiency are candidates for treatment with
      programmed cell death protein 1 inhibition.Genomic testing of recurrent,
      advanced, or metastatic tumors may be useful to determine whether patients are
      candidates for precision therapies.

PMID- 29472313
TI  - Luminal A Breast Cancer and Molecular Assays: A Review.
AB  - PURPOSE: Chemotherapy has been the historical mainstay of treatment for patients
      with breast cancer, with immunohistochemical markers and tumor characteristics
      driving treatment decisions. The discovery of different intrinsic subtypes of
      breast cancer has advanced the understanding of breast cancer, with gene-based
      assays shedding further light on tumor behavior and response to treatment.
      DESIGN: This review focuses on the landscape of the luminal A subtype, its
      definition based on immunohistochemistry (IHC) and gene assays, the prognostic
      and predictive value of these assays, guideline recommendations, and treatment
      implications. RESULTS: Clinical studies of the prognostic value of gene-based and
      IHC-based assays in patients with luminal A-subtype breast cancers suggest a
      better prognosis for these patients compared with those with breast cancers of
      other subtypes. CONCLUSION: In today's era of precision medicine, the best
      treatment regimen for patients with luminal A-subtype tumors is still
      undetermined, but available data raise the question whether chemotherapy can be
      omitted and endocrine therapy alone is sufficient for this patient population.
      IMPLICATIONS FOR PRACTICE: Immunohistochemical markers have traditionally guided
      treatment decisions in breast cancer. However, advances in gene-expression
      profiling and availability of gene-based assays have launched these newer tests
      into everyday clinical practice. Luminal A-subtype tumors are a unique subset
      that may have favorable tumor biology. Properly defining this tumor subtype is
      important and may identify a subset of patients for whom endocrine therapy alone
      is sufficient.

PMID- 29472314
TI  - Cysteine modifiers suggest an allosteric inhibitory site on the CAL PDZ domain.
AB  - Protein-protein interactions have become attractive targets for both experimental
      and therapeutic interventions. The PSD-95/Dlg1/ZO-1 (PDZ) domain is found in a
      large family of eukaryotic scaffold proteins that plays important roles in
      intracellular trafficking and localization of many target proteins. Here, we seek
      inhibitors of the PDZ protein that facilitates post-endocytic degradation of the
      cystic fibrosis (CF) transmembrane conductance regulator (CFTR): the CFTR
      associated ligand (CAL). We develop and validate biochemical screens and identify
      methyl-3,4-dephostatin (MD) and its analog ethyl-3,4-dephostatin (ED) as CAL PDZ
      inhibitors. Depending on conditions, MD can bind either covalently or non
      covalently. Crystallographic and NMR data confirm that MD attacks a pocket at a
      site distinct from the canonical peptide-binding groove, and suggests an
      allosteric connection between target residue Cys319 and the conserved Leu291 in
      the GLGI motif. MD and ED thus appear to represent the first examples of small
      molecule allosteric regulation of PDZ:peptide affinity. Their mechanism of action
      may exploit the known conformational plasticity of the PDZ domains and suggests
      that allosteric modulation may represent a strategy for targeting of this family
      of protein-protein binding modules.

PMID- 29472316
TI  - Border crossings: joining a multidisciplinary conversation about medical
      humanities.

PMID- 29472315
TI  - Prognostic values of aquaporins mRNA expression in human ovarian cancer.
AB  - Aquaporins (AQPs), a family of transmembrane channel, are composed of 13
      identified members (AQP0-12). Accumulating evidences reported that AQPs were
      correlated with various biological roles and represented a prognostic predictor
      in various cancer types. However, the prognostic value of AQPs expression in
      ovarian cancer remains unclear. Using 'Kaplan-Meier plotter' (KM plotter) online
      database, we explored the predictive prognostic value of individual AQPs members'
      mRNA expression to overall survival (OS) in different clinical data, such as
      histology, pathological grades, clinical stages, TP53 status, and applied
      chemotherapy in ovarian cancer patients. Our results revealed that higher AQP0,
      AQP1, and AQP4 mRNA expression were correlated with poor OS, whereas higher AQP3,
      AQP5, AQP6, AQP8, AQP10, and AQP11 showed better OS in ovarian cancer patients.
      Moreover, AQP4 and AQP8 showed poor OS in TP53-mutated ovarian cancer patients
      and AQP1 presented unfavorable OS in both TP53 mutated and wild ovarian cancer
      patients. Additionally, AQP3, AQP6, and AQP11 mRNA expression were correlated
      with better OS, whereas AQP0 and AQP1 showed poor OS in all ovarian cancer
      patients treated with Platin, Taxol, and Taxol + Platin chemotherapy. AQP5, AQP8,
      and AQP10 were associated with improved OS, however, AQP4 predicted unfavorable
      OS in all patients treated with Platin chemotherapy. Our results suggest that
      individual AQPs, except AQP2 and AQP9, are associated with unique prognostic
      significance and may thus act as new predictive prognostic indicators and
      potential drug therapeutic target in ovarian cancer.

PMID- 29472317
TI  - Dynamic Control of Chromosome Topology and Gene Expression by a Chromatin
      Modification.
AB  - The function of chromatin modification in establishing higher-order chromosome
      structure during gene regulation has been elusive. We dissected the machinery and
      mechanism underlying the enrichment of histone modification H4K20me1 on
      hermaphrodite X chromosomes during Caenorhabditis elegans dosage compensation and
      discovered a key role for H4K20me1 in regulating X-chromosome topology and
      chromosome-wide gene expression. Structural and functional analysis of the dosage
      compensation complex (DCC) subunit DPY-21 revealed a novel Jumonji C demethylase
      subfamily that converts H4K20me2 to H4K20me1 in worms and mammals. Inactivation
      of demethylase activity in vivo by genome editing eliminated H4K20me1 enrichment
      on X chromosomes of somatic cells, increased X-linked gene expression, reduced X
      chromosome compaction, and disrupted X-chromosome conformation by diminishing the
      formation of topologically associated domains. H4K20me1 is also enriched on the
      inactive X of female mice, making our studies directly relevant to mammalian
      development. Unexpectedly, DPY-21 also associates specifically with autosomes of
      nematode germ cells in a DCC-independent manner to enrich H4K20me1 and trigger
      chromosome compaction. Thus, DPY-21 is an adaptable chromatin regulator. Its
      H4K20me2 demethylase activity can be harnessed during development for distinct
      biological functions by targeting it to diverse genomic locations through
      different mechanisms. In both somatic cells and germ cells, H4K20me1 enrichment
      modulates three-dimensional chromosome architecture, demonstrating the direct
      link between chromatin modification and higher-order chromosome structure.

PMID- 29472319
TI  - Draft Genome Sequence of an Isolate of Colletotrichum fructicola, a Causal Agent
      of Mango Anthracnose.
AB  - Here, we present a draft genome sequence of isolate 15060 of Colletotrichum
      fructicola, a causal agent of mango anthracnose. The final assembly consists of
      1,048 scaffolds totaling 56,493,063 bp (G+C content, 53.38%) and 15,180 predicted
      genes.

PMID- 29472318
TI  - Fork Protection and Therapy Resistance in Hereditary Breast Cancer.
AB  - The BRCA-Fanconi anemia (FA) pathway preserves the genome and suppresses cancer
      and is a main determinant of chemotherapeutic efficacy. The hereditary breast
      cancer genes BRCA1 and BRCA2 function in DNA double-strand break repair mediating
      distinct steps of homologous recombination (HR). More recently, independent of
      DNA repair, functions in the replication stress response have come to light,
      providing insight as to how the BRCA-FA pathway also balances genome preservation
      with proliferation. The BRCA-FA proteins associate with the replisome and
      contribute to the efficiency and recovery of replication following perturbations
      that slow or arrest DNA replication. Although the full repertoire of functions in
      the replication stress response remains to be elucidated, the function of BRCA1
      and BRCA2 in protecting stalled replication forks contributes along with HR to
      the sensitivity of BRCA-associated tumors to chemotherapy. Moreover,
      chemoresistance evolves from restoration of either HR and/or fork protection.
      Although mechanisms underlying the restoration of HR have been characterized, it
      remains less clear how restoration of fork protection is achieved. Here, we
      outline mechanisms of "rewired" fork protection and chemotherapy resistance in
      BRCA cancer. We propose that mechanisms are linked to permissive replication that
      limits fork remodeling and therefore opportunities for fork degradation.
      Combating this chemoresistance mechanism will require drugs that inactivate
      replication bypass mechanisms.

PMID- 29472320
TI  - Draft Genome Sequence of a Novel Thermofilum sp. Strain from a New Zealand Hot
      Spring Enrichment Culture.
AB  - A draft genome of a new Thermofilum sp. strain was obtained from an enrichment
      culture metagenome. Like its relatives, Thermofilum sp. strain NZ13 is adapted to
      organic-rich thermal environments and has to depend on other organisms and the
      environment for some key amino acids, purines, and cofactors.

PMID- 29472321
TI  - Complete Genome Sequence of vB_BveP-Goe6, a Virus Infecting Bacillus velezensis
      FZB42.
AB  - The new virus vB_BveP-Goe6 was isolated on the host organism Bacillus velezensis
      FZB42. The virus morphology indicated its association with the genus Phi29virus
      The genome of vB_BveP-Goe6 (19,105 bp) comprises a linear chromosome with a GC
      content of 39.99%. The genome harbors 26 putative protein-coding genes and a
      noncoding packaging RNA.

PMID- 29472322
TI  - Complete Genome Sequences of pLMA1 and pLMA7, Two Large Linear Plasmids of
      Micrococcus Strains Isolated from a High-Altitude Lake in Argentina.
AB  - The two linear plasmids pLMA1 (109,112 bp) and pLMA7 (82,075 bp) from Micrococcus
      strains were isolated from a high-altitude lake in the Argentinean Puna,
      sequenced, and annotated. These extrachromosomal elements are probably
      conjugative and harbor genes potentially involved in coping with the harsh
      conditions in such extreme environments.

PMID- 29472323
TI  - Complete Genome Sequence of the Facultative Methylotroph Methylobacterium
      extorquens TK 0001 Isolated from Soil in Poland.
AB  - Methylobacterium extorquens TK 0001 (DSM 1337, ATCC 43645) is an aerobic pink
      pigmented facultative methylotrophic alphaproteobacterium isolated from soil in
      Poland. Here, we report the whole-genome sequence and annotation of this
      organism, which consists of a single 5.71-Mb chromosome.

PMID- 29472324
TI  - Complete Genome Sequence of Xanthomonas arboricola pv. juglandis Strain DW3F3,
      Isolated from a Juglans regia L. Bacterial Blighted Fruitlet.
AB  - Here, we report the complete genome sequence of Xanthomonas arboricola pv.
      juglandis DW3F3, a strong pathogenic strain isolated from blighted walnut
      immature fruit (Juglans regia L. cv. Qingxiang). The genome consists of a single
      chromosome (5,144 kb).

PMID- 29472325
TI  - Draft Genome Sequences of blaKPC-Containing Enterobacter aerogenes, Citrobacter
      freundii, and Citrobacter koseri Strains.
AB  - We report here the draft genome sequences of four blaKPC-containing bacteria
      identified as Klebsiella aerogenes, Citrobacter freundii, and Citrobacter koseri
      Additionally, we report the draft genome sequence of a K. aerogenes strain that
      did not contain a blaKPC gene but was isolated from the patient who had the
      blaKPC-2-containing K. aerogenes strain.

PMID- 29472326
TI  - Complete Genome Sequences of 11 Type Species from the Thermococcus Genus of
      Hyperthermophilic and Piezophilic Archaea.
AB  - We report here the genome sequences of the type strains of the species
      Thermococcus barossii, T. celer, T. chitonophagus, T. gorgonarius, T. pacificus,
      T. peptonophilus, T. profundus, T. radiotolerans, T. siculi, and T. thioreducens,
      as well as the prototype of a possible type strain of a novel Thermococcus
      species, strain P6.

PMID- 29472327
TI  - Draft Genome Sequence of Methylocella silvestris TVC, a Facultative Methanotroph
      Isolated from Permafrost.
AB  - Permafrost environments play a crucial role in global carbon and methane cycling.
      We report here the draft genome sequence of Methylocella silvestris TVC, a new
      facultative methanotroph strain, isolated from the Siksik Creek catchment in the
      continuous permafrost zone of Inuvik (Northwest Territories, Canada).

PMID- 29472328
TI  - Draft Genome Sequence of a Propanotroph, Rhodococcus sp. Strain ENV425, Capable
      of Degrading Methyl tert-Butyl Ether and N-Nitrosodimethylamine.
AB  - In this study, the draft genome of Rhodococcus sp. strain ENV425 was determined.
      The propane-grown strain ENV425 cometabolically degrades environmental
      contaminants such as methyl tert-butyl ether and N-nitrosodimethylamine. The
      sequence revealed the presence of multiple hydrocarbon metabolic genes that could
      play pivotal roles in the biodegradation of pollutants.

PMID- 29472329
TI  - Draft Genome Sequence of Bacillus sp. Strain UFRGS-B20, a Hydrocarbon Degrader.
AB  - Bacillus sp. strain UFRGS-B20 was isolated in 2012 from Brazilian land-farming
      soil contaminated with petrochemical oily sludge. This strain was subjected to
      hydrocarbon biodegradation tests, showing degradation rates of up to 60%. Here,
      we present the 6.82-Mb draft genome sequence of the strain, which contains 2,178
      proteins with functional assignments.

PMID- 29472330
TI  - First Report of a Complete Genome Sequence of White spot syndrome virus from
      India.
AB  - White spot syndrome virus is a major pathogen of shrimp, causing economic loss to
      the aquaculture industry. For the first time, a complete de novo genome of an
      Indian isolate of this virus has been deciphered using Illumina and Nanopore
      sequencing technologies. The genome has 280,591 bp with 442 predicted coding
      genes.

PMID- 29472331
TI  - Complete Genome Sequence of Escherichia coli 81009, a Representative of the
      Sequence Type 131 C1-M27 Clade with a Multidrug-Resistant Phenotype.
AB  - The sequence type 131 (ST131)-H30 clone is responsible for a significant
      proportion of multidrug-resistant extraintestinal Escherichia coli infections.
      Recently, the C1-M27 clade of ST131-H30, associated with blaCTX-M-27, has
      emerged. The complete genome sequence of E. coli isolate 81009 belonging to this
      clone, previously used during the development of ST131-specific monoclonal
      antibodies, is reported here.

PMID- 29472332
TI  - Complete Genome Sequence of a New Strain of Tanay Virus, Isolate YN15_103_01,
      from Yunnan, China.
AB  - We report here the complete genome sequence of a new strain of Tanay virus,
      isolate YN15_103_01, which was isolated from Anopheles sinensis mosquitoes caught
      in China. Sequence analysis showed that it shares a 79% nucleotide sequence
      identity with the only other previously reported strains of Tanay virus, which
      were isolated from the Philippines.

PMID- 29472333
TI  - Complete Genome Sequences of Two Porcine Enterotoxigenic Escherichia coli
      Strains.
AB  - Enterotoxigenic Escherichia coli (ETEC) is one of the main causes of illness and
      death in neonatal and recently weaned pigs. Here, we sequenced the genomes of two
      ETEC strains that were previously used as inactivated vaccines in China.

PMID- 29472334
TI  - Complete Genome Sequence of a Fusarium graminearum Double-Stranded RNA Virus in a
      Newly Proposed Family, Alternaviridae.
AB  - We describe here a double-stranded RNA mycovirus, termed Fusarium graminearum
      alternavirus 1 (FgAV1/AH11), from the isolate AH11 of the phytopathogenic fungus
      F. graminearum Phylogenetic analysis showed that FgAV1/AH11 belongs to a newly
      proposed family, Alternaviridae This is the first report of a mycovirus in the
      family Alternaviridae that infects F. graminearum.

PMID- 29472335
TI  - Complete Genome Sequence of Lactococcus lactis subsp. lactis G50 with
      Immunostimulating Activity, Isolated from Napier Grass.
AB  - Lactococcus lactis subsp. lactis G50 is a strain with immunostimulating activity,
      isolated from Napier grass (Pennisetum purpureum). We determined the complete
      genome sequence of this strain using the PacBio RS II platform. The single
      circular chromosome consists of 2,346,663 bp, with 35.03% G+C content and no
      plasmids.

PMID- 29472336
TI  - Draft Genome Sequence of Clostridium sp. Strain chh4-2 Isolated from Human Feces.
AB  - Here, we report the draft genome sequence of a Clostridium sp. strain isolated
      from a fecal sample of a 34-year-old adult male in Taiwan. This strain may
      represent a new bacterium, as suggested by a comparison based on whole-genome
      sequencing. The genome assembly comprised 6,089,737 bp, with a 45.63% G+C
      content.

PMID- 29472337
TI  - Draft Genome Sequence of Micromonospora sp. Strain WMMA1996, a Marine Sponge
      Associated Bacterium.
AB  - Micromonospora sp. strain WMMA1996 was isolated in 2013 off the coast of the
      Florida Keys, United States, from a marine sponge as part of bacterial coculture
      based drug discovery initiatives. Analysis of the ~6.44-Mb genome reveals this
      microbe's potential role in the discovery of new drugs.

PMID- 29472338
TI  - Genome Sequence of a Marine Alkane Degrader, Alcanivorax sp. Strain 97CO-6.
AB  - Alcanivorax sp. strain 97CO-6 was isolated from a crude oil-consuming bacterial
      consortium, enriched from Yellow Sea sediments from China. Here, we present the
      draft genome of strain 97CO-6, which contains 3,253,423 bp, with a G+C content of
      54.53%, as well as 2,931 protein-coding genes and 42 tRNAs.

PMID- 29472339
TI  - Genome Sequence of Azospirillum brasilense REC3, Isolated from Strawberry Plants.
AB  - The genome sequence of a plant growth-promoting bacterium and biocontrol agent,
      Azospirillum brasilense REC3, isolated from strawberry roots, is reported here.
      The A. brasilense REC3 total genome contains 7,229,924 bp and has a G+C content
      of 68.7 mol%.

PMID- 29472340
TI  - Complete Genome Sequence of EtG, the First Phage Sequenced from Erwinia
      tracheiphila.
AB  - Erwinia tracheiphila is the causal agent of bacterial wilt of cucurbits. Here, we
      report the genome sequence of the temperate phage EtG, which was isolated from an
      E. tracheiphila-infected cucumber plant. Phage EtG has a linear 30,413-bp double
      stranded DNA genome with cohesive ends and 45 predicted open reading frames.

PMID- 29472341
TI  - Genomic Sequence of Mycobacteriophage OKCentral2016.
AB  - OKCentral2016 is the first mycobacteriophage sequenced from Oklahoma soil using
      the bacterial host Mycobacterium smegmatis strain mc2155. OKCentral2016 has a
      double-stranded DNA genome composed of 50,072 bp, with 84 predicted coding genes
      and 1 tRNA sequence. This mycobacteriophage has sequence similarities to members
      of the A10 subcluster.

PMID- 29472342
TI  - Full-Length Genome Sequences of Recombinant and Nonrecombinant Sympatric Strains
      of Rice yellow mottle virus from Western Kenya.
AB  - Five isolates of Rice yellow mottle virus from western Kenya were fully
      sequenced. One isolate of strain S4lv had been collected in 1966. Two isolates
      belonged to the emerging strain S4ug recently described in Uganda. Two isolates
      collected in 2012 are putative recombinants between the S4lv and S4ug strains.

PMID- 29472343
TI  - Draft Genome Sequence of Sphingobacterium sp. Strain HMA12, Which Encodes Endo
      beta-N-Acetylglucosaminidases and Can Specifically Hydrolyze Fucose-Containing
      Oligosaccharides.
AB  - The genome sequence of the soil bacterium Sphingobacterium sp. strain HMA12, the
      culture supernatant of which exhibited endo-beta-N-acetylglucosaminidase (ENGase)
      activity, was examined for ENGase-encoding genes. Here, we report the
      characterization of new genes of ENGases, obtained by whole-genome shotgun
      sequencing, that are capable of specifically hydrolyzing fucose-containing
      oligosaccharides.

PMID- 29472344
TI  - Complete Genome Sequence of Actinobacillus succinogenes GXAS137, a Highly
      Efficient Producer of Succinic Acid.
AB  - The bacterium Actinobacillus succinogenes GXAS137, an efficient producer of
      succinic acid, was isolated from bovine rumen in Nanning, Guangxi Province,
      China. Here, we present the 2.3-Mb genome assembly of this strain, which consists
      of 2,314,479 bp (G+C content of 44.89%) with a circular chromosome, 2,235 DNA
      coding sequences, 57 tRNAs, and 15 rRNAs.

PMID- 29472345
TI  - Draft Genome Sequence of Microcystis aeruginosa NIES-87, a Bloom-Forming
      Cyanobacterium from Lake Kasumigaura, Japan.
AB  - Microcystis aeruginosa is a problematic cyanobacterium in freshwater lakes
      distributed worldwide. Here, we report the draft genome sequence of M. aeruginosa
      NIES-87, isolated from Lake Kasumigaura, Japan. The genome is approximately 4.9
      Mb in size, with an average G+C content of 42.9% and 4,355 predicted protein
      coding genes.

PMID- 29472346
TI  - Draft Genome Sequence of an Extracellular Protease-Producing Bacterium,
      Stenotrophomonas bentonitica VV6, Isolated from Arctic Seawater.
AB  - The draft genome sequence of the extracellular protease-producing bacterium
      Stenotrophomonas bentonitica VV6, isolated from Arctic seawater, was established.
      The genome size was approximately 4.365 Mb, with a G+C content of 66.54%, and it
      contains 3,871 predicted protein-coding sequences (CDSs) and 60 tRNAs.

PMID- 29472347
TI  - Single-agent dabrafenib for BRAFV600E-mutated histiocytosis.

PMID- 29472348
TI  - Liquid biopsy for the identification of intravascular large B-cell lymphoma.

PMID- 29472350
TI  - Memory CD8+ T cells support the maintenance of hematopoietic stem cells in the
      bone marrow.

PMID- 29472349
TI  - Clinical relevance of IDH1/2 mutant allele burden during follow-up in acute
      myeloid leukemia. A study by the French ALFA group.
AB  - Assessment of minimal residual disease has emerged as a powerful prognostic
      factor in acute myeloid leukemia. In this study, we investigated the potential of
      IDH1/2 mutations as targets for minimal residual disease assessment in acute
      myeloid leukemia, since these mutations collectively occur in 15-20% of cases of
      acute myeloid leukemia and now represent druggable targets. We employed droplet
      digital polymerase chain reaction assays to quantify IDH1R132, IDH2R140, and
      IDH2R172 mutations on genomic DNA in 322 samples from 103 adult patients with
      primary IDH1/2 mutant acute myeloid leukemia and enrolled on Acute Leukemia
      French Association (ALFA) - 0701 or -0702 clinical trials. The median IDH1/2
      mutant allele fraction in bone marrow samples was 42.3% (range, 8.2 - 49.9%) at
      diagnosis of acute myeloid leukemia, and below the detection limit of 0.2%
      (range, <0.2 - 39.3%) in complete remission after induction therapy. In
      univariate analysis, the presence of a normal karyotype, a NPM1 mutation, and an
      IDH1/2 mutant allele fraction <0.2% in bone marrow after induction therapy were
      statistically significant predictors of longer disease-free survival. In
      multivariate analysis, these three variables remained significantly predictive of
      disease-free survival. In 7/103 (7%) patients, IDH1/2 mutations persisted at high
      levels in complete remission, consistent with the presence of an IDH1/2 mutation
      in pre-leukemic hematopoietic stem cells. Five out of these seven patients
      subsequently relapsed or progressed toward myelodysplastic syndrome, suggesting
      that patients carrying the IDH1/2 mutation in a pre-leukemic clone may be at high
      risk of hematologic evolution.

PMID- 29472351
TI  - Impact of histological grading on survival in the SWOG S0016 follicular lymphoma
      cohort.

PMID- 29472352
TI  - Ibrutinib withdrawal symptoms in patients with Waldenstrom macroglobulinemia.

PMID- 29472354
TI  - Efficacy and safety of high-dose etoposide cytarabine as consolidation following
      rituximab methotrexate temozolomide induction in newly diagnosed primary central
      nervous system lymphoma in immunocompetent patients.

PMID- 29472353
TI  - Long-term management of leukocyte adhesion deficiency type III without
      hematopoietic stem cell transplantation.

PMID- 29472355
TI  - Use of thrombin generation assay to personalize treatment of breakthrough bleeds
      in a patient with hemophilia and inhibitors receiving prophylaxis with
      emicizumab.

PMID- 29472356
TI  - A B-cell receptor-related gene signature predicts survival in mantle cell
      lymphoma: results from the Fondazione Italiana Linfomi MCL-0208 trial.
AB  - Mantle cell lymphoma patients have variable clinical courses, ranging from
      indolent cases that do not require immediate treatment to aggressive, rapidly
      progressing diseases. Thus, diagnostic tools capable of stratifying patients
      according to their risk of relapse and death are needed. This study included 83
      samples from the Fondazione Italiana Linfomi MCL-0208 clinical trial. Through
      gene expression profiling and quantitative real-time PCR we analyzed 46
      peripheral blood and 43 formalin-fixed paraffin-embedded lymph node samples. A
      prediction model to classify patients was developed. By analyzing the
      transcriptome of 27 peripheral blood samples, two subgroups characterized by a
      differential expression of genes from the B-cell receptor pathway (B-cell
      receptorlow and B-cell receptorhigh) were identified. The prediction model based
      on the quantitative real-time PCR values of six representative genes (AKT3, BCL2,
      BTK, CD79B, PIK3CD, and SYK), was used to classify the 83 cases (43 B-cell
      receptorlow and 40 B-cell receptorhigh). The B-cell receptorhigh signature
      associated with shorter progression-free survival (P=0.0074), selected the mantle
      cell lymphoma subgroup with the shortest progression-free survival and overall
      survival (P=0.0014 and P=0.029, respectively) in combination with high (>30%) Ki
      67 staining, and was an independent predictor of short progression- free survival
      along with the Mantle Cell Lymphoma International Prognostic Index-combined
      score. Moreover, the clinical impact of the 6- gene signature related to the B
      cell receptor pathway identified a mantle cell lymphoma subset with shorter
      progression-free survival intervals also in an external independent mantle cell
      lymphoma cohort homogenously treated with different schedules. In conclusion,
      this 6-gene signature associates with a poor clinical response in the context of
      the MCL- 0208 clinical trial. (clinicaltrials.gov identifier: 02354313).

PMID- 29472357
TI  - Plerixafor enables safe, rapid, efficient mobilization of hematopoietic stem
      cells in sickle cell disease patients after exchange transfusion.
AB  - Sickle cell disease is characterized by chronic anemia and vaso-occlusive crises,
      which eventually lead to multi-organ damage and premature death. Hematopoietic
      stem cell transplantation is the only curative treatment but it is limited by
      toxicity and poor availability of HLA-compatible donors. A gene therapy approach
      based on the autologous transplantation of lentiviral-corrected hematopoietic
      stem and progenitor cells was shown to be efficacious in one patient. However,
      alterations of the bone marrow environment and properties of the red blood cells
      hamper the harvesting and immunoselection of patients' stem cells from bone
      marrow. The use of Filgrastim to mobilize large numbers of hematopoietic stem and
      progenitor cells into the circulation has been associated with severe adverse
      events in sickle cell patients. Thus, broader application of the gene therapy
      approach requires the development of alternative mobilization methods. We set up
      a phase I/II clinical trial whose primary objective was to assess the safety of a
      single injection of Plerixafor in sickle cell patients undergoing red blood cell
      exchange to decrease the hemoglobin S level to below 30%. The secondary objective
      was to measure the efficiency of mobilization and isolation of hematopoietic stem
      and progenitor cells. No adverse events were observed. Large numbers of CD34+
      cells were mobilized extremely quickly. Importantly, the mobilized cells
      contained high numbers of hematopoietic stem cells, expressed high levels of
      stemness genes, and engrafted very efficiently in immunodeficient mice. Thus,
      Plerixafor can be safely used to mobilize hematopoietic stem cells in sickle cell
      patients; this finding opens up new avenues for treatment approaches based on
      gene addition and genome editing. Clinicaltrials.gov identifier: NCT02212535.

PMID- 29472358
TI  - Circulating tumor DNA as a liquid biopsy in plasma cell dyscrasias.

PMID- 29472359
TI  - Usefulness of initial plasma dabigatran concentration to predict rebound after
      reversal.

PMID- 29472360
TI  - Immobilized fibrinogen activates human platelets through glycoprotein VI.
AB  - Glycoprotein VI, a major platelet activation receptor for collagen and fibrin, is
      considered a particularly promising, safe antithrombotic target. In this study,
      we show that human glycoprotein VI signals upon platelet adhesion to fibrinogen.
      Full spreading of human platelets on fibrinogen was abolished in platelets from
      glycoprotein VI- deficient patients suggesting that fibrinogen activates
      platelets through glycoprotein VI. While mouse platelets failed to spread on
      fibrinogen, human-glycoprotein VI-transgenic mouse platelets showed full
      spreading and increased Ca2+ signaling through the tyrosine kinase Syk. Direct
      binding of fibrinogen to human glycoprotein VI was shown by surface plasmon
      resonance and by increased adhesion to fibrinogen of human glycoprotein VI
      transfected RBL-2H3 cells relative to mock-transfected cells. Blockade of human
      glycoprotein VI with the Fab of the monoclonal antibody 9O12 impaired platelet
      aggregation on preformed platelet aggregates in flowing blood independent of
      collagen and fibrin exposure. These results demonstrate that human glycoprotein
      VI binds to immobilized fibrinogen and show that this contributes to platelet
      spreading and platelet aggregation under flow.

PMID- 29472361
TI  - A second-generation 15-PGDH inhibitor promotes bone marrow transplant recovery
      independently of age, transplant dose and granulocyte colony-stimulating factor
      support.
AB  - Hematopoietic stem cell transplantation following myeloablative chemotherapy is a
      curative treatment for many hematopoietic malignancies. However, profound
      granulocytopenia during the interval between transplantation and marrow recovery
      exposes recipients to risks of fatal infection, a significant source of
      transplant-associated morbidity and mortality. We have previously described the
      discovery of a small molecule, SW033291, that potently inhibits the prostaglandin
      degrading enzyme 15-PGDH, increases bone marrow prostaglandin E2, and accelerates
      hematopoietic recovery following murine transplant. Here we describe the efficacy
      of (+)-SW209415, a second-generation 15-PGDH inhibitor, in an expanded range of
      models relevant to human transplantation. (+)-SW209415 is 10,000-fold more
      soluble, providing the potential for intravenous delivery, while maintaining
      potency in inhibiting 15-PGDH, increasing in vivo prostaglandin E2, and
      accelerating hematopoietic regeneration following transplantation. In additional
      models, (+)-SW209415: (i) demonstrated synergy with granulocyte colony
      stimulating factor, the current standard of care; (ii) maintained efficacy as
      transplant cell dose was escalated; (iii) maintained efficacy when transplant
      donors and recipients were aged; and (iv) potentiated homing in xenotransplants
      using human hematopoietic stem cells. (+)-SW209415 showed no adverse effects, no
      potentiation of in vivo growth of human myeloma and leukemia xenografts, and, on
      chronic high-dose administration, no toxicity as assessed by weight, blood counts
      and serum chemistry. These studies provide independent chemical confirmation of
      the activity of 15-PGDH inhibitors in potentiating hematopoietic recovery, extend
      the range of models in which inhibiting 15-PGDH demonstrates activity, allay
      concerns regarding potential for adverse effects from increasing prostaglandin
      E2, and thereby, advance 15-PGDH as a therapeutic target for potentiating
      hematopoietic stem cell transplantation.

PMID- 29472363
TI  - Examination of the elephant.

PMID- 29472362
TI  - Open-label, multicentre, dose-escalating phase II clinical trial on the safety
      and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease.
AB  - OBJECTIVES: Adult-onset Still's disease (AOSD) is a rare systemic
      autoinflammatory disease; its management is largely empirical. This is the first
      clinical study to determine if interleukin (IL)-18 inhibition, using the
      recombinant human IL-18 binding protein, tadekinig alfa, is a therapeutic option
      in AOSD. METHODS: In this phase II, open-label study, patients were >=18 years
      with active AOSD plus fever or C reactive protein (CRP) levels >=10 mg/L despite
      treatment with prednisone and/or conventional synthetic disease-modifying
      antirheumatic drugs (DMARDs). Previous biological DMARD treatment was permitted.
      Patients received tadekinig alfa 80 mg or 160 mg subcutaneously three times per
      week for 12 weeks; those receiving 80 mg not achieving early predicted response
      criteria (reduction of >=50% CRP values from baseline and fever resolution) were
      up-titrated to 160 mg for a further 12 weeks. The primary endpoint was the
      occurrence of adverse events (AEs) throughout the study. RESULTS: Ten patients
      were assigned to receive 80 mg tadekinig alfa and 13 patients to the 160 mg dose.
      One hundred and fifty-five treatment-emerging AEs were recorded, and 47 were
      considered related to the study drug. Most AEs were mild and resolved after drug
      discontinuation. Three serious AEs occurred, one possibly related to treatment
      (toxic optic neuropathy). At week 3, 5 of 10 patients receiving 80 mg and 6 of 12
      patients receiving 160 mg achieved the predefined response criteria. CONCLUSIONS:
      Our results indicate that tadekinig alfa appears to have a favourable safety
      profile and is associated with early signs of efficacy in patients with AOSD.
      TRIAL REGISTRATION NUMBER: NCT02398435.

PMID- 29472364
TI  - Pseudo-DUBs as allosteric activators and molecular scaffolds of protein
      complexes.
AB  - The ubiquitin (Ub) proteasome system and Ub signalling networks are crucial to
      cell biology and disease development. Deubiquitylases (DUBs) control cell
      signalling by removing mono-Ub and polyubiquitin chains from substrates. DUBs
      take part in almost all processes that regulate cellular life and are frequently
      dysregulated in disease. We have catalogued 99 currently known DUBs in the human
      genome and sequence conservation analyses of catalytic residues suggest that 11
      lack enzyme activity and are classed as pseudo-DUBs. These pseudoenzymes play
      important biological roles by allosterically activating catalytically competent
      DUBs as well as other active enzymes. Additionally, pseudoenzymes act as assembly
      scaffolds of macromolecular complexes. We discuss how pseudo-DUBs have lost their
      catalytic activity, their diverse mechanisms of action and their potential as
      therapeutic targets. Many known pseudo-DUBs play crucial roles in cell biology
      and it is likely that unstudied and overlooked pseudo-DUB genes will have equally
      important functions.

PMID- 29472365
TI  - Lysosomal membrane permeabilization as a cell death mechanism in cancer cells.
AB  - Lysosomes are acidic organelles that contain hydrolytic enzymes that mediate the
      intracellular degradation of macromolecules. Damage of these organelles often
      results in lysosomal membrane permeabilization (LMP) and the release into the
      cytoplasm of the soluble lysosomal contents, which include proteolytic enzymes of
      the cathepsin family. This, in turn, activates several intracellular cascades
      that promote a type of regulated cell death, called lysosome-dependent cell death
      (LDCD). LDCD can be inhibited by pharmacological or genetic blockade of cathepsin
      activity, or by protecting the lysosomal membrane, thereby stabilizing the
      organelle. Lysosomal alterations are common in cancer cells and may increase the
      sensitivity of these cells to agents that promote LMP. In this review, we
      summarize recent findings supporting the use of LDCD as a means of killing cancer
      cells.

PMID- 29472366
TI  - Competitive resource allocation to metabolic pathways contributes to overflow
      metabolisms and emergent properties in cross-feeding microbial consortia.
AB  - Resource scarcity is a common stress in nature and has a major impact on
      microbial physiology. This review highlights microbial acclimations to resource
      scarcity, focusing on resource investment strategies for chemoheterotrophs from
      the molecular level to the pathway level. Competitive resource allocation
      strategies often lead to a phenotype known as overflow metabolism; the resulting
      overflow byproducts can stabilize cooperative interactions in microbial
      communities and can lead to cross-feeding consortia. These consortia can exhibit
      emergent properties such as enhanced resource usage and biomass productivity. The
      literature distilled here draws parallels between in silico and laboratory
      studies and ties them together with ecological theories to better understand
      microbial stress responses and mutualistic consortia functioning.

PMID- 29472367
TI  - Model-based metabolism design: constraints for kinetic and stoichiometric models.
AB  - The implementation of model-based designs in metabolic engineering and synthetic
      biology may fail. One of the reasons for this failure is that only a part of the
      real-world complexity is included in models. Still, some knowledge can be
      simplified and taken into account in the form of optimization constraints to
      improve the feasibility of model-based designs of metabolic pathways in
      organisms. Some constraints (mass balance, energy balance, and steady-state
      assumption) serve as a basis for many modelling approaches. There are others
      (total enzyme activity constraint and homeostatic constraint) proposed decades
      ago, but which are frequently ignored in design development. Several new
      approaches of cellular analysis have made possible the application of constraints
      like cell size, surface, and resource balance. Constraints for kinetic and
      stoichiometric models are grouped according to their applicability preconditions
      in (1) general constraints, (2) organism-level constraints, and (3) experiment
      level constraints. General constraints are universal and are applicable for any
      system. Organism-level constraints are applicable for biological systems and
      usually are organism-specific, but these constraints can be applied without
      information about experimental conditions. To apply experimental-level
      constraints, peculiarities of the organism and the experimental set-up have to be
      taken into account to calculate the values of constraints. The limitations of
      applicability of particular constraints for kinetic and stoichiometric models are
      addressed.

PMID- 29472368
TI  - Signaling through plant lectins: modulation of plant immunity and beyond.
AB  - Lectins constitute an abundant group of proteins that are present throughout the
      plant kingdom. Only recently, genome-wide screenings have unraveled the multitude
      of different lectin sequences within one plant species. It appears that plants
      employ a plurality of lectins, though relatively few lectins have already been
      studied and functionally characterized. Therefore, it is very likely that the
      full potential of lectin genes in plants is underrated. This review summarizes
      the knowledge of plasma membrane-bound lectins in different biological processes
      (such as recognition of pathogen-derived molecules and symbiosis) and illustrates
      the significance of soluble intracellular lectins and how they can contribute to
      plant signaling. Altogether, the family of plant lectins is highly complex with
      an enormous diversity in biochemical properties and activities.

PMID- 29472370
TI  - Dual PI3K blockade: PTCL's Achilles heel?

PMID- 29472371
TI  - How does hepcidin hinder ferroportin activity?

PMID- 29472369
TI  - Diverse exocytic pathways for mast cell mediators.
AB  - Mast cells play pivotal roles in innate and adaptive immunities but are also
      culprits in allergy, autoimmunity, and cardiovascular diseases. Mast cells
      respond to environmental changes by initiating regulated exocytosis/secretion of
      various biologically active compounds called mediators (e.g. proteases, amines,
      and cytokines). Many of these mediators are stored in granules/lysosomes and rely
      on intricate degranulation processes for release. Mast cell stabilizers (e.g.
      sodium cromoglicate), which prevent such degranulation processes, have therefore
      been clinically employed to treat asthma and allergic rhinitis. However, it has
      become increasingly clear that different mast cell diseases often involve
      multiple mediators that rely on overlapping but distinct mechanisms for release.
      This review illustrates existing evidence that highlights the diverse exocytic
      pathways in mast cells. We also discuss strategies to delineate these pathways so
      as to identify unique molecular components which could serve as new drug targets
      for more effective and specific treatments against mast cell-related diseases.

PMID- 29472372
TI  - VWF clearance: it's glycomplicated.

PMID- 29472373
TI  - HSCT for PID: not just for children.

PMID- 29472374
TI  - Chewing the bone: bone marrow with adult T-cell leukemia/lymphoma.

PMID- 29472375
TI  - B-cell acute lymphoblastic leukemia in JAK2 V617F-positive polycythemia vera.

PMID- 29472376
TI  - Clinical relevance of different WHO grade 3 pancreatic neuroendocrine neoplasms
      based on morphology.
AB  - PURPOSE: Emerging evidence suggests G3 pancreatic neuroendocrine neoplasms
      (pNENs) present heterogeneous morphology and biology. The 2017 WHO classification
      has introduced a new category of well-differentiated pancreatic neuroendocrine
      tumors (WD-pNETs) G3, compared with poorly differentiated pancreatic
      neuroendocrine carcinomas (PD-pNECs) G3. We aim to analysis the demographics and
      outcomes of patients with resectable 2017 WHO G3 pNENs to facilitate the
      distinction between two entities. METHODS: The multi-institutional retrospective
      cohort involving 57 surgically treated patients affected by 2017 WHO G3 pNENs
      were morphologically identified and clinically analyzed. Patients having WD-pNETs
      G3 and those having PD-pNECs G3 were compared. RESULTS: Thirty patients had WD
      pNETs and 27 patients had PD-pNECs. The distributions of Ki-67 and mitotic count
      in patients with PD-pNECs or WD-pNETs showed remarkable disparities. ROC
      indicated cut-off value of Ki-67 was 45. PD-pNECs were more common in patients
      with elevated Ki-67 and mitotic count, advanced AJCC TNM stage, vascular
      invasion, regional lymph-node metastases, elevated NSE and decreased CgA levels
      compared with WD-pNETs (P < 0.05). The association between 2017 WHO G3 grade and
      TTR was statistically significant (P < 0.05). Univariate analysis indicated OS
      rates were associated with morphologic differentiation (WD-pNETs vs PD-pNECs), Ki
      67, TNM staging, synchronous distant metastases, initial treatments, vascular
      invasion, regional lymph nodes metastases, mitotic count and age (P < 0.05).
      Multivariate analyses illustrated Ki-67, differentiation, TNM staging and
      vascular invasion were independent predictors (P < 0.05). CONCLUSIONS: PD-pNECs
      G3 presented malignant biological behavior and dismal outcome compared with WD
      pNETs G3. These findings challenge 2010 WHO classification and suggest the
      categorization can be improved by refined tumor grading.

PMID- 29472377
TI  - TAAR1 induces a disturbed GSK3beta phosphorylation in recurrent miscarriages
      through the ODC.
AB  - OBJECTIVES: Thyroid hormones play an important role in the maintenance of
      pregnancy. Their derivates, endogenous amines, act via binding to the trace amine
      associated receptor (TAAR1). The aim of our study was to analyse the regulation
      of TAAR1, serine/threonine kinase (pGSK3beta) and ornithine decarboxylase (ODC)
      in placentas of healthy pregnancies, spontaneous (SM) and recurrent miscarriages
      (RM) and to investigate the influence of thyroid hormone derivates on TAAR1
      expression in trophoblast model cells in vitro. METHODS: Patients with SM (n =
      15) and RM (n = 15) were compared with patients with healthy pregnancies (n = 15)
      (pregnancy weeks 7-13 each). Immunohistochemistry was applied to analyse
      placental TAAR1, pGSK3beta and ODC expression. Protein expression of the
      receptors after stimulation with T3, T1AM and RO5203548 in BeWo trophoblast model
      cells was determined via Western blot. Double-immunofluorescence was used to
      determine placental expression of TAAR1 and ODC. RESULTS: Levels of TAAR1,
      pGSK3beta and ODC were higher in placentas of RM in comparison to healthy
      controls. Stimulation of BeWo cells with T3, T1AM and RO5203548 significantly
      increased TAAR1 expression. ODC expression in BeWo cells was upregulated through
      T3. Via double-immunofluorescence, TAAR1 and ODC-positive EVT could be detected.
      CONCLUSIONS: Upregulation of placental TAAR1 may indicate an increased
      decarboxylation of thyroid hormones in miscarriages. Patients with RM may have a
      lack of T3 through an enhanced transformation of T3 into T1AM induced by the ODC.
      Future investigations could be carried out to analyse what role a prophylactic T3
      substitution plays for patients.

PMID- 29472379
TI  - DIAGNOSIS OF ENDOCRINE DISEASE: The role of the desmopressin test in the
      diagnosis and follow-up of Cushing's syndrome.
AB  - Desmopressin is a vasopressin analogue selective for type 2 vasopressin receptors
      that mediate renal water retention. In contrast to the native hormone arginine
      vasopressin, a well-known ACTH secretagogue, desmopressin, exerts minimal or no
      activity on ACTH excretion. However, in a substantial proportion of patients with
      ACTH-dependent Cushing's syndrome (CS), desmopressin elicits an ACTH and cortisol
      response, which contrasts with the minimal responses obtained in healthy
      subjects. The mechanism underlying this paradoxical response involves
      upregulation of vasopressin type 3 and/or the aberrant expression of type 2
      receptors by neoplastic ACTH-producing cells. This makes desmopressin
      administration a suitable test enabling the distinction between neoplastic from
      functional (formerly termed 'pseudo-Cushing syndrome') ACTH-dependent cortisol
      excess. Several studies have now established an adjunctive role of desmopressin
      in the initial diagnostic workup of CS. Despite some early data indicating that
      this test may also have a role in distinguishing between Cushing's disease (CD)
      and ectopic ACTH secretion, subsequent studies failed to confirm this
      observation. The ability of the paradoxical response to desmopressin to depict
      the presence of neoplastic ACTH-secreting cells was also exploited in the follow
      up of patients with CD undergoing surgery. Loss of the desmopressin response,
      performed in the early postoperative period, was a good predictor for a favorable
      long-term outcome. Moreover, during follow-up, reappearance of desmopressin
      paradoxical response was an early indicator for recurrence. In conclusion, the
      desmopressin test is a valid tool in both the diagnosis and follow-up of patients
      with CD and should be more widely applied in the workup of these patients.

PMID- 29472378
TI  - Hepatic safety of ketoconazole in Cushing's syndrome: results of a Compassionate
      Use Programme in France.
AB  - OBJECTIVE: Ketoconazole (KTZ) is one of few available treatments for Cushing's
      syndrome (CS). Although KTZ has been associated with severe hepatotoxicity,
      little information is available about hepatic safety in CS. The aim of this study
      was to document changes in liver function in patients with CS treated with KTZ.
      DESIGN: An observational prospective French cohort study (Compassionate Use
      Programme (CUP)). METHODS: Enrolled patients were stratified into a KTZ-naive
      cohort and a cohort already treated by another formulation of ketoconazole (KTZ
      switch cohort). Liver function markers (alanine transaminase (ALT), aspartate
      transaminase (AST), alkaline phosphatase, gamma-glutamyltransferase and
      bilirubin) were monitored at regular intervals. Patients with ALT > 3 * ULN
      (upper limit of normal), total bilirubin > 2 * ULN or both ALP > 2 * ULN and ALT
      > ULN were considered to have liver injury. RESULTS: Overall, 108 patients were
      analysed (47 KTZ-naive; 61 KTZ-switch). The median KTZ dose was 600 mg/day. Most
      abnormalities observed were asymptomatic mild increases of liver enzymes. Four
      patients in the KTZ-naive cohort (8.5%) and two in the KTZ-switch cohort (3.3%)
      developed liver injury, considered related to KTZ in three cases (all KTZ-naive
      in the first month of treatment). Five patients had mild liver function
      abnormalities at baseline and two had proven liver metastases. Two patients
      recovered on discontinuation of KTZ and the remaining patient died of unrelated
      causes. CONCLUSIONS: These findings highlight the need for close monitoring of
      liver enzymes especially during the first six months of treatment. Liver enzyme
      abnormalities usually occurred within four weeks were asymptomatic and could be
      reversed on timely discontinuation of KTZ.

PMID- 29472381
TI  - Deactivation of 12(S)-HETE through (omega-1)-hydroxylation and beta-oxidation in
      alternatively activated macrophages.
AB  - Polarization of macrophages to proinflammatory M1 and to antiinflammatory
      alternatively activated M2 states has physiological implications in the
      development of experimental hypertension and other pathological conditions. 12/15
      Lipoxygenase (12/15-LO) and its enzymatic products 12(S)- and 15(S)
      hydroxyeicosatetraenoic acid (HETE) are essential in the process since disruption
      of the gene encoding 12/15-LO renders the mice unsusceptible to hypertension. The
      objective was to test the hypothesis that M2 macrophages catabolize 12(S)-HETE
      into products that are incapable of promoting vasoconstriction. Cultured M2
      macrophages metabolized externally added [14C]12(S)-HETE into more polar
      metabolites, while M1 macrophages had little effect on the catabolism. The major
      metabolites were identified by mass spectrometry as (omega-1)-hydroxylation and
      beta-oxidation products. The conversion was inhibited by both peroxisomal beta
      oxidation inhibitor, thioridazine, and cytochrome P450 inhibitors. Quantitative
      PCR analysis confirmed that several cytochrome P450 enzymes (CYP2E1 and CYP1B1)
      and peroxisomal beta-oxidation markers were upregulated upon M2 polarization. The
      identified 12,19-dihydroxy-5,8,10,14-eicosatetraenoic acid and 8-hydroxy-6,10
      hexadecadienoic acid metabolites were tested on abdominal aortic rings for
      biological activity. While 12(S)-HETE enhanced vasoconstrictions to angiotensin
      II from 15% to 25%, the metabolites did not. These results indicate that M2, but
      not M1, macrophages degrade 12(S)-HETE into products that no longer enhance the
      angiotensin II-induced vascular constriction, supporting a possible
      antihypertensive role of M2 macrophages.

PMID- 29472382
TI  - Dopamine D2 receptor upregulates leptin and IL-6 in adipocytes.
AB  - Leptin is a pro-inflammatory cytokine secreted by the adipose tissue. Dopamine D2
      receptors (D2Rs) have anti-inflammatory effects in the brain and kidney tissues.
      Mouse and human adipocytes express D2R; D2R protein was 10-fold greater in
      adipocytes from human visceral tissue than subcutaneous tissue. However, the
      function of D2R in adipocytes is not well understood. 3T3-L1 cells were treated
      with D2-like receptor agonist quinpirole, and immunoblot and quantitative PCR
      were performed. Quinpirole increased the protein and mRNA expression of leptin
      and IL-6, but not adiponectin and visfatin (24 h). It also increased the mRNA
      expression of TNF-alpha , MCP1, and NFkB-p50. An acute increase in the protein
      expression of leptin and TNF-alpha was also found in the cells treated with
      quinpirole. The leptin concentration in the culture media was increased by
      quinpirole-bathing the 3T3-L1 adipocytes. These quinpirole effects on leptin and
      IL-6 expression were prevented by the D2R antagonist L741,626. Similarly, siRNA
      mediated silencing of Drd2 decreased the leptin, IL-6, mRNA, and protein
      expressions. The D2R-mediated increase in leptin expression was prevented by the
      phosphoinositide 3-kinase inhibitor LY294002. Acute quinpirole treatment in
      C57Bl/6J mice increased serum leptin concentration and leptin mRNA in visceral
      adipocyte tissue but not in subcutaneous adipocytes, confirming the stimulatory
      effect of D2R on leptin in vivo. Our results suggest that the stimulation of D2R
      increases leptin production and may have a tissue-specific pro-inflammatory
      effect in adipocytes.

PMID- 29472383
TI  - Making sense of the clinical spectrum of limb girdle muscular dystrophies.
AB  - The expansion of the spectrum of limb girdle muscular dystrophies (LGMDs) in
      recent years means that neurologists need to be familiar with the clinical clues
      that can help with their diagnosis. The LGMDs comprise a group of genetic
      myopathies that manifest as chronic progressive weakness of hip and shoulder
      girdles. Their inheritance is either autosomal dominant (LGMD1) or autosomal
      recessive (LGMD2). Their prevalence varies in different regions of the world;
      certain ethnic groups have documented founder mutations and this knowledge can
      facilitate the diagnosis. The clinical approach to LGMDs uses the age at onset,
      genetic transmission and clinical patterns of muscular weakness. Helpful clinical
      features that help to differentiate the various subtypes include: predominant
      upper girdle weakness, disproportionate respiratory muscle involvement, distal
      weakness, hip adductor weakness, 'biceps lump' and 'diamond on quadriceps' sign,
      calf hypertrophy, contractures and cardiac involvement. Almost half of patients
      with LGMD have such clinical clues. Investigations such as serum creatine kinase,
      electrophysiology, muscle biopsy and genetic studies can complement the clinical
      examination. In this review, we discuss diagnostic clinical pointers and comment
      on the differential diagnosis and relevant investigations, using illustrative
      case studies.

PMID- 29472384
TI  - Neuropsychological testing.
AB  - Neuropsychological testing is a key diagnostic tool for assessing people with
      dementia and mild cognitive impairment, but can also help in other neurological
      conditions such as Parkinson's disease, stroke, multiple sclerosis, traumatic
      brain injury and epilepsy. While cognitive screening tests offer gross
      information, detailed neuropsychological evaluation can provide data on different
      cognitive domains (visuospatial function, memory, attention, executive function,
      language and praxis) as well as neuropsychiatric and behavioural features. We
      should regard neuropsychological testing as an extension of the neurological
      examination applied to higher order cortical function, since each cognitive
      domain has an anatomical substrate. Ideally, neurologists should discuss the
      indications and results of neuropsychological assessment with a clinical
      neuropsychologist. This paper summarises the rationale, indications, main
      features, most common tests and pitfalls in neuropsychological evaluation.

PMID- 29472385
TI  - Laura Lackner: Passing on the scientific baton.
AB  - Lackner investigates the tethering processes that position mitochondria.

PMID- 29472380
TI  - Spontaneous Coronary Artery Dissection: Current State of the Science: A
      Scientific Statement From the American Heart Association.
AB  - Spontaneous coronary artery dissection (SCAD) has emerged as an important cause
      of acute coronary syndrome, myocardial infarction, and sudden death, particularly
      among young women and individuals with few conventional atherosclerotic risk
      factors. Patient-initiated research has spurred increased awareness of SCAD, and
      improved diagnostic capabilities and findings from large case series have led to
      changes in approaches to initial and long-term management and increasing evidence
      that SCAD not only is more common than previously believed but also must be
      evaluated and treated differently from atherosclerotic myocardial infarction.
      High rates of recurrent SCAD; its association with female sex, pregnancy, and
      physical and emotional stress triggers; and concurrent systemic arteriopathies,
      particularly fibromuscular dysplasia, highlight the differences in clinical
      characteristics of SCAD compared with atherosclerotic disease. Recent insights
      into the causes of, clinical course of, treatment options for, outcomes of, and
      associated conditions of SCAD and the many persistent knowledge gaps are
      presented.

PMID- 29472386
TI  - PI(4,5)P2 controls plasma membrane PI4P and PS levels via ORP5/8 recruitment to
      ER-PM contact sites.
AB  - Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a critically important
      regulatory lipid of the plasma membrane (PM); however, little is known about how
      cells regulate PM PI(4,5)P2 levels. Here, we show that the phosphatidylinositol 4
      phosphate (PI4P)/phosphatidylserine (PS) transfer activity of the endoplasmic
      reticulum (ER)-resident ORP5 and ORP8 is regulated by both PM PI4P and PI(4,5)P2
      Dynamic control of ORP5/8 recruitment to the PM occurs through interactions with
      the N-terminal Pleckstrin homology domains and adjacent basic residues of ORP5/8
      with both PI4P and PI(4,5)P2 Although ORP5 activity requires normal levels of
      these inositides, ORP8 is called on only when PI(4,5)P2 levels are increased.
      Regulation of the ORP5/8 attachment to the PM by both phosphoinositides provides
      a powerful means to determine the relative flux of PI4P toward the ER for PS
      transport and Sac1-mediated dephosphorylation and PIP 5-kinase-mediated
      conversion to PI(4,5)P2 Using this rheostat, cells can maintain PI(4,5)P2 levels
      by adjusting the availability of PI4P in the PM.

PMID- 29472388
TI  - No turning back on TB.

PMID- 29472389
TI  - Focus turns to badgers as government launches new consultations on bovine TB.

PMID- 29472387
TI  - Class IIa histone deacetylases link cAMP signaling to the myelin transcriptional
      program of Schwann cells.
AB  - Schwann cells respond to cyclic adenosine monophosphate (cAMP) halting
      proliferation and expressing myelin proteins. Here we show that cAMP signaling
      induces the nuclear shuttling of the class IIa histone deacetylase (HDAC)-4 in
      these cells, where it binds to the promoter and blocks the expression of c-Jun, a
      negative regulator of myelination. To do it, HDAC4 does not interfere with the
      transcriptional activity of MEF2. Instead, by interacting with NCoR1, it recruits
      HDAC3 and deacetylates histone 3 in the promoter of c-Jun, blocking gene
      expression. Importantly, this is enough to up-regulate Krox20 and start Schwann
      cell differentiation program-inducing myelin gene expression. Using conditional
      knockout mice, we also show that HDAC4 together with HDAC5 redundantly contribute
      to activate the myelin transcriptional program and the development of myelin
      sheath in vivo. We propose a model in which cAMP signaling shuttles class IIa
      HDACs into the nucleus of Schwann cells to regulate the initial steps of
      myelination in the peripheral nervous system.

PMID- 29472392
TI  - Vet teams suffering from lack of self-belief.

PMID- 29472393
TI  - Exciting new discovery for the chytrid mystery.
AB  - The emerging infectious disease chytridiomycosis, caused by the fungal pathogen
      Batrachochytrium dendrobatidis, is thought to affect over 500 amphibian species
      worldwide. But, as Georgina Mills explains, new research has now shed light on
      what could make some individuals more susceptible.

PMID- 29472396
TI  - Mycoplasma bovis infection causing arthritis and pneumonia in cattle.

PMID- 29472397
TI  - An insight into digital radiography use in small animal practice in the UK.

PMID- 29472398
TI  - Investigating and managing abdominal trauma in dogs.

PMID- 29472401
TI  - How to improve your salary.

PMID- 29472402
TI  - How to improve your salary.

PMID- 29472403
TI  - Is there actually a gender pay gap?

PMID- 29472404
TI  - Current draft legislation.

PMID- 29472405
TI  - Animal welfare post-Brexit.

PMID- 29472406
TI  - Is there actually a gender pay gap?

PMID- 29472407
TI  - Why do dogs eat poo?

PMID- 29472408
TI  - Make helmets a policy.

PMID- 29472409
TI  - Animal welfare post-Brexit.

PMID- 29472410
TI  - We should be straight talking on salaries.

PMID- 29472411
TI  - William Clifton Botcherby.
AB  - A vet with an unconventional approach to life, Clif Botcherby was always ready to
      help others and was 'a great boss'. He was a keen golfer and was passionate about
      Robert Burns.

PMID- 29472414
TI  - Laminin-521 Protein Therapy for Glomerular Basement Membrane and Podocyte
      Abnormalities in a Model of Pierson Syndrome.
AB  - Background Laminin alpha5beta2gamma1 (LM-521) is a major component of the GBM.
      Mutations in LAMB2 that prevent LM-521 synthesis and/or secretion cause Pierson
      syndrome, a rare congenital nephrotic syndrome with diffuse mesangial sclerosis
      and ocular and neurologic defects. Because the GBM is uniquely accessible to
      plasma, which permeates endothelial cell fenestrae, we hypothesized that
      intravenous delivery of LM-521 could replace the missing LM-521 in the GBM of
      Lamb2 mutant mice and restore glomerular permselectivity.Methods We injected
      human LM-521 (hLM-521), a macromolecule of approximately 800 kD, into the retro
      orbital sinus of Lamb2-/- pups daily. Deposition of hLM-521 into the GBM was
      investigated by fluorescence microscopy. We assayed the effects of hLM-521 on
      glomerular permselectivity by urinalysis and the effects on podocytes by desmin
      immunostaining and ultrastructural analysis of podocyte architecture.Results
      Injected hLM-521 rapidly and stably accumulated in the GBM of all glomeruli.
      Super-resolution imaging showed that hLM-521 accumulated in the correct
      orientation in the GBM, primarily on the endothelial aspect. Treatment with hLM
      521 greatly reduced the expression of the podocyte injury marker desmin and
      attenuated the foot process effacement observed in untreated pups. Moreover,
      treatment with hLM-521 delayed the onset of proteinuria but did not prevent
      nephrotic syndrome, perhaps due to its absence from the podocyte aspect of the
      GBM.Conclusions These studies show that GBM composition and function can be
      altered in vivovia vascular delivery of even very large proteins, which may
      advance therapeutic options for patients with abnormal GBM composition, whether
      genetic or acquired.

PMID- 29472415
TI  - Cluster-Randomized Trial of Devices to Prevent Catheter-Related Bloodstream
      Infection.
AB  - Central venous catheters (CVCs) contribute disproportionately to bloodstream
      infection (BSI) and, by extension, to infection-related hospitalization,
      mortality, and health care costs in patients undergoing dialysis. Recent product
      advancements may reduce BSIs, but a sufficiently powered comparative
      effectiveness study is needed to facilitate evidence-based patient care
      decisions. In a 13-month, prospective, cluster-randomized, open-label trial, we
      compared BSI rates in facilities using ClearGuard HD antimicrobial barrier caps
      (ClearGuard group) with those in facilities using Tego hemodialysis connectors
      plus Curos disinfecting caps (Tego+Curos group). Forty DaVita dialysis facilities
      in the United States were pair-matched by BSI rate, number of patients using
      CVCs, and geographic location, and then cluster randomized 1:1. We enrolled all
      adult patients undergoing dialysis with CVCs at these facilities, except those
      allergic to heparin or chlorhexidine. Overall, 1671 patients participated in the
      study, accruing >183,000 CVC-days. The study outcome was positive blood culture
      (PBC) rate as an indicator of BSI rate. We calculated results at the cluster
      level and adjusted for the facility cluster effect. During a 3-month run-in
      period immediately before study interventions, the groups had similar BSI rates
      (P=0.8). During the 13-month intervention period that immediately followed, the
      ClearGuard group had a BSI rate significantly lower than that of the Tego+Curos
      group (0.28 versus 0.75 PBCs per 1000 CVC-days, respectively; P=0.001). No device
      related adverse events were reported. In conclusion, compared with Tego
      connectors plus Curos caps, ClearGuard HD antimicrobial barrier caps
      significantly lowered the rate of catheter-related BSIs in patients undergoing
      hemodialysis using CVCs, representing an important advancement in hemodialysis
      patient care.

PMID- 29472416
TI  - Biomarkers of AKI Progression after Pediatric Cardiac Surgery.
AB  - Background As children progress to higher stages of AKI, the risk for adverse
      outcomes dramatically increases. No reliable methods exist to predict AKI
      progression in hospitalized children. To determine if biomarkers of inflammation
      and kidney injury can predict AKI progression, we conducted a three-center
      prospective cohort study of children undergoing cardiopulmonary bypass.Methods On
      the first day of serum creatinine-defined AKI, we measured urine biomarkers
      (neutrophil gelatinase-associated lipocalin [NGAL], IL-18, kidney injury molecule
      1, liver fatty acid binding protein [L-FABP], albumin, and cystatin C) and plasma
      biomarkers (IFN, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-alpha,
      NGAL, and cystatin C). We defined AKI progression as a worsening of AKI stage or
      persisting stage 3 AKI (>=2 consecutive days).Results In all, 176 of 408 (43%)
      children developed postoperative AKI. Among the children with AKI, we diagnosed
      stages 1, 2, and 3 AKI in 145 (82.5%), 25 (14%), and six (3.5%) children,
      respectively, on the first day of AKI; 28 (7%) children had AKI progression. On
      the first day of AKI, nine of 17 biomarkers were significantly higher in patients
      with than without AKI progression. Urine L-FABP (among injury biomarkers) and
      plasma IL-8 (among inflammatory biomarkers) had the highest discrimination for
      AKI progression: optimism-corrected area under the curve, 0.70; 95% confidence
      interval, 0.58 to 0.81 and optimism-corrected area under the curve, 0.80; 95%
      confidence interval, 0.69 to 0.91, respectively.Conclusions If validated in
      additional cohorts, plasma IL-8 could be used to improve clinical care and guide
      enrollment in therapeutic trials of AKI.

PMID- 29472418
TI  - Bullous eyelid.
AB  - Periocular necrotising fasciitis is a rare but sight-threatening condition, which
      relies on clinical judgement to detect in a timely manner. A 51-year-old woman
      presented to a rural hospital with rapid onset bilateral eye swelling, erythema
      and pain and was started on broad spectrum intravenous antibiotics. Upon
      admission, she became septic and required fluid resuscitation and transfer to a
      higher level of care. She received debridement and continued intravenous
      antibiotics, with step down to oral when clinically stable. Rapid recognition and
      treatment of her condition resulted in a positive outcome.

PMID- 29472419
TI  - A womb like a broken heart.
AB  - Uterine perforation during hysteroscopic operative procedures is a potential
      complication well known to gynaecologists. Uterine septa are a commonly
      encountered Mullerian anomaly related to pregnancy loss and infertility.
      Hysteroscopic resection of septa has shown to improve pregnancy outcome. There
      are limited case reports of uterine rupture in subsequent pregnancies after
      hysteroscopic septal resection. Our patient had a hysteroscopic septal resection
      done a year prior which was complicated by a uterine fundal perforation, left to
      spontaneously heal after immediate sealing with cautery. The patient conceived
      spontaneously soon after and underwent an emergency caesarean section for severe
      pre-eclampsia. Intraoperatively, after removal of the placenta, we discovered a 3
      cm symmetrical circular defect at the fundus of the uterus with no myometrium or
      serosa. The potentially disastrous consequences of this silent uterine rupture
      were mitigated due to another life-threatening condition which prevented the
      onset of labour.

PMID- 29472417
TI  - HDL in CKD-The Devil Is in the Detail.
AB  - The picture of HDL cholesterol (HDL-C) as the "good" cholesterol has eroded. This
      is even more surprising because there exists strong evidence that HDL-C is
      associated with cardiovascular disease (CVD) in the general population as well as
      in patients with impairment of kidney function and/or progression of CKD.
      However, drugs that dramatically increase HDL-C have mostly failed to decrease
      CVD events. Furthermore, genetic studies took the same line, as genetic variants
      that have a pronounced influence on HDL-C concentrations did not show an
      association with cardiovascular risk. For many, this was not surprising, given
      that an HDL particle is highly complex and carries >80 proteins and several
      hundred lipid species. Simply measuring cholesterol might not reflect the variety
      of biologic effects of heterogeneous HDL particles. Therefore, functional studies
      and the involvement of HDL components in the reverse cholesterol transport,
      including the cholesterol efflux capacity, have become a further focus of study
      during recent years. As also observed for other aspects, CKD populations behave
      differently compared with non-CKD populations. Although clear disturbances have
      been observed for the "functionality" of HDL particles in patients with CKD, this
      did not necessarily translate into clear-cut associations with outcomes.

PMID- 29472420
TI  - Budd-Chiari syndrome in a patient with ulcerative colitis.
AB  - We report a case of 26-year-old man who was admitted on our ward for the
      evaluation of ascites. He was a known case of inflammatory bowel
      disease(ulcerative colitis) and was on regular mesalamine therapy. On evaluation,
      he was having high serum ascites albumin gradient. CT scan of the abdomen
      revealed features of portal hypertension and non-visualisation of right and
      middle hepatic veins along with thrombus in inferior vena cava, suggesting a
      diagnosis of Budd-Chiari syndrome (BCS). There are only few case reports
      available showing association of BCS with UC. Hence, we are reporting this
      interesting and rare case.

PMID- 29472421
TI  - Mycobacterium ChelonaeDeveloping Multidrug Resistance.
AB  - Mycobacterium chelonae is a rapidly growing mycobacterium which is known to
      respond well to standard antibiotic treatment regimen. There are no specific
      guidelines for treatment. Antibiotics are chosen based on the bacterial
      sensitivity. Here we present a 47-year-old man with hip replacement who developed
      bright red papular generalised skin lesions and bilateral hip abscess. On workup,
      it was confirmed that M. chelonae was the causative organism. He was given 8
      weeks of antibiotics; however, there was worsening of the hip abscess on interval
      imaging. The progression was most likely due to M. chelonae developing antibiotic
      resistance. Physicians should be aware of the rising resistance of this organism,
      and guide antibiotic therapy based on bacterial sensitivity to yield better
      outcomes.

PMID- 29472422
TI  - Prolonged paralysis with atracurium use in a patient with Rubinstein-Taybi
      syndrome.
AB  - Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disorder that occurs
      due to a microdeletion of chromosome 16p13. The craniofacial abnormalities in
      these patients may pose a challenge for anaesthetist performing tracheal
      intubation. However, there are no known reported cases of drug interaction with
      non-depolarising muscle relaxant in patients with RTS. This young patient with
      RTS presented with an unexpected prolonged atracurium effect during the course of
      anaesthesia. After ruling out other possible causes, we have come to a conclusion
      that RTS itself could have played a role in the prolonged effect of atracurium.
      However, further studies will be needed to confirm this hypothesis. In the
      meantime, care should be used when using muscle relaxants in patients with RTS.

PMID- 29472423
TI  - Dieulafoy's lesion of the duodenum: a comparative review of 37 cases.
AB  - Dieulafoy's lesion is an abnormally large, tortuous, submucosal vessel that
      erodes the overlying epithelium without primary ulceration or erosion. The lesion
      predominantly occurs in the proximal stomach but it is also reported in
      extragastric sites. The pathogenesis and precipitating factors are poorly
      understood. Patients frequently present with gastrointestinal haemorrhage that
      can range from being self-limited to massive life threatening. Although there are
      no standard guidelines, endoscopy has significantly impacted the diagnosis and
      management. This review outlines our current understanding of the epidemiology of
      and risk factors for Dieulafoy's lesion of the duodenum, the pathophysiology of
      this disorder, and currently available approaches to diagnosis and management.

PMID- 29472424
TI  - Pentobarbital-induced lactic acidosis following status epilepticus barbiturate
      coma.
AB  - We present a rare case of pentobarbital infusion causing propylene glycol-induced
      lactic acidosis, during refractory status epilepticus treatment in a 66-year-old
      man without seizure history.

PMID- 29472425
TI  - Sublingual microcirculation reveals fluid overload and leukocytosis in a post
      cardiac surgery patient.

PMID- 29472426
TI  - Uncommon cause of hypercalcaemia in metastatic breast carcinoma.

PMID- 29472427
TI  - Bilateral vulval filarial elephantiasis.

PMID- 29472428
TI  - Calcium sign of thoracic aortic dissection in Takayasu's arteritis.

PMID- 29472429
TI  - Wicked problems, complex solutions, and the cost of trust.

PMID- 29472431
TI  - Zygodactyly (Syndactyly Type A1) Associated With Midfoot Charcot Neuropathy and
      Diabetes.

PMID- 29472430
TI  - In Vivo Phosphoproteome Analysis Reveals Kinome Reprogramming in Hepatocellular
      Carcinoma.
AB  - Aberrant kinases contribute to cancer survival and proliferation. Here, we
      quantitatively characterized phosphoproteomic changes in an HBx-transgenic mouse
      model of hepatocellular carcinoma (HCC) using high-resolution mass spectrometry,
      profiled 22,539 phosphorylation sites on 5431 proteins. Using a strategy to
      interpret kinase- substrate relations in HCC and to uncover predominant kinases
      in tumors, our results, revealed elevated kinase activities of Src family kinases
      (SFKs), PKCs, MAPKs, and ROCK2 in HCC, representatives of which were further
      validated in cell models and clinical HBV-positive HCC samples. Inhibitor
      combinations targeting Src and PKCs or ROCK2 both synergized significantly to
      inhibit cell growth. In addition, we demonstrated that phosphorylation at Src
      Ser17 directly affects its kinase activity. Our phosphoproteome data facilitated
      the construction of a detailed molecular landscape in HCC and should serve as a
      resource for the cancer community. Our strategy is generally applicable to
      targeted therapeutics, also highlights potential mechanisms of kinase regulation.

PMID- 29472432
TI  - Predicting the Effect of Fenofibrate on Cardiovascular Risk for Individual
      Patients With Type 2 Diabetes.
AB  - OBJECTIVE: In clinical trials, treatment with fenofibrate did not reduce the
      incidence of major cardiovascular events (MCVE) in patients with type 2 diabetes
      mellitus (T2DM). However, treatment effects reported by trials comprise patients
      who respond poorly and patients who respond well to fenofibrate. Our aim was to
      use statistical modeling to estimate the expected treatment effect of fenofibrate
      for individual patients with T2DM. RESEARCH DESIGN AND METHODS: To estimate
      individual risk, the FIELD risk model, with 5-year MCVE as primary outcome, was
      externally validated in T2DM patients from ACCORD and the SMART observational
      cohort. Fenofibrate treatment effect was estimated in 17,142 T2DM patients from
      FIELD, ACCORD, and SMART. Individual treatment effect, expressed as absolute risk
      reduction (ARR), is the difference between treated and untreated MCVE risk.
      Results were stratified for patients with and without dyslipidemia (i.e., high
      triglycerides and low LDL cholesterol). RESULTS: External validation of the FIELD
      risk model showed good calibration and moderate discrimination in ACCORD (C
      statistic 0.67 [95% CI 0.65-0.69]) and SMART (C-statistic 0.66 [95% CI 0.63
      0.69]). Median 5-year MCVE risk in all three studies combined was 6.7%
      (interquartile range [IQR] 4.0-11.7) in patients without (N = 13,224) and 9.4%
      (IQR 5.4-16.1%) in patients with (N = 3,918) dyslipidemia. The median ARR was
      2.15% (IQR 1.23-3.68) in patients with dyslipidemia, corresponding with a number
      needed to treat (NNT) of 47, and 0.22% (IQR 0.13-0.38) in patients without
      dyslipidemia (NNT 455). CONCLUSIONS: In individual patients with T2DM, there is a
      wide range of absolute treatment effect of fenofibrate, and overall the
      fenofibrate treatment effect was larger in patients with dyslipidemia. The method
      of individualized treatment effect prediction of fenofibrate on MCVE risk
      reduction in T2DM can be used to guide clinical decision making.

PMID- 29472433
TI  - Photo Quiz: Isolation of a "Friendly Bacterium" from a Pyogenic Liver Abscess.

PMID- 29472434
TI  - Answer to March 2018 Photo Quiz.

PMID- 29472435
TI  - The Brief Case: Disseminated Histoplasma capsulatum in a Patient with Newly
      Diagnosed HIV Infection/AIDS.

PMID- 29472436
TI  - Closing the Brief Case: Disseminated Histoplasma capsulatum in a Patient with
      Newly Diagnosed HIV Infection/AIDS.

PMID- 29472437
TI  - External Quality Assessment (EQA) of Molecular Detection of Zika Virus: Value of
      the 1st World Health Organization International Standard.

PMID- 29472438
TI  - Reply to Baylis et al., "External Quality Assessment (EQA) of Molecular Detection
      of Zika Virus: Value of the 1st World Health Organization International
      Standard".

PMID- 29472439
TI  - Commercial porcine reproductive and respiratory syndrome virus (PRRSV)-2 modified
      live virus vaccine against heterologous single and dual Korean PRRSV-1 and PRRSV
      2 challenge.
AB  - This study evaluated porcine reproductive and respiratory syndrome virus (PRRSV)
      2 modified live virus (MLV) vaccine against heterologous single and dual
      challenge of Korean PRRSV-1 and PRRSV-2. Pigs were administered PRRSV-2 MLV
      vaccine intramuscularly at 21 days of age and inoculated intranasally with both
      genotypes at 56 days of age. Vaccination of pigs with PRRSV-2 MLV vaccine
      resulted in reduction of viral loads of both PRRSV-1 and PRRSV-2 after
      heterologous single and dual challenge with PRRSV-1 and PRRSV-2. In addition,
      pigs vaccinated with PRRSV-2 MLV vaccine exhibited higher frequencies of PRRSV-1
      and PRRSV-2 specific interferon-gamma secreting cells (IFN-gamma-SC) and showed a
      significant reduction in lung lesions and PRRSV nucleic acid within the lung
      lesions after single and dual challenge compared with unvaccinated challenged
      pigs. Taken together these results demonstrated that vaccination of pigs with
      PRRSV-2 is efficacious in protecting growing pigs from respiratory disease
      against heterologous single and dual PRRSV-1 and PRRSV-2 challenge.

PMID- 29472440
TI  - Recurrences in an isolated quantum many-body system.
AB  - The complexity of interacting quantum many-body systems leads to exceedingly long
      recurrence times of the initial quantum state for all but the smallest systems.
      For large systems, one cannot probe the full quantum state in all its details.
      Thus, experimentally, recurrences can only be determined on the level of the
      accessible observables. Realizing a commensurate spectrum of collective
      excitations in one-dimensional superfluids, we demonstrate recurrences of
      coherence and long-range order in an interacting quantum many-body system
      containing thousands of particles. Our findings will enable the study of the
      coherent dynamics of large quantum systems even after they have reached a
      transient thermal-like state.

PMID- 29472441
TI  - Early emergence of cortical interneuron diversity in the mouse embryo.
AB  - GABAergic interneurons (GABA, gamma-aminobutyric acid) regulate neural-circuit
      activity in the mammalian cerebral cortex. These cortical interneurons are
      structurally and functionally diverse. Here, we use single-cell transcriptomics
      to study the origins of this diversity in the mouse. We identify distinct types
      of progenitor cells and newborn neurons in the ganglionic eminences, the
      embryonic proliferative regions that give rise to cortical interneurons. These
      embryonic precursors show temporally and spatially restricted transcriptional
      patterns that lead to different classes of interneurons in the adult cerebral
      cortex. Our findings suggest that shortly after the interneurons become
      postmitotic, their diversity is already patent in their diverse transcriptional
      programs, which subsequently guide further differentiation in the developing
      cortex.

PMID- 29472443
TI  - Real-time imaging of DNA loop extrusion by condensin.
AB  - It has been hypothesized that SMC protein complexes such as condensin and cohesin
      spatially organize chromosomes by extruding DNA into large loops. We directly
      visualized the formation and processive extension of DNA loops by yeast condensin
      in real time. Our findings constitute unambiguous evidence for loop extrusion. We
      observed that a single condensin complex is able to extrude tens of kilobase
      pairs of DNA at a force-dependent speed of up to 1500 base pairs per second,
      using the energy of adenosine triphosphate hydrolysis. Condensin-induced loop
      extrusion was strictly asymmetric, which demonstrates that condensin anchors onto
      DNA and reels it in from only one side. Active DNA loop extrusion by SMC
      complexes may provide the universal unifying principle for genome organization.

PMID- 29472442
TI  - Ancient genomes revisit the ancestry of domestic and Przewalski's horses.
AB  - The Eneolithic Botai culture of the Central Asian steppes provides the earliest
      archaeological evidence for horse husbandry, ~5500 years ago, but the exact
      nature of early horse domestication remains controversial. We generated 42
      ancient-horse genomes, including 20 from Botai. Compared to 46 published ancient-
      and modern-horse genomes, our data indicate that Przewalski's horses are the
      feral descendants of horses herded at Botai and not truly wild horses. All
      domestic horses dated from ~4000 years ago to present only show ~2.7% of Botai
      related ancestry. This indicates that a massive genomic turnover underpins the
      expansion of the horse stock that gave rise to modern domesticates, which
      coincides with large-scale human population expansions during the Early Bronze
      Age.

PMID- 29472444
TI  - Adolescent tobacco coupon receipt, vulnerability characteristics and subsequent
      tobacco use: analysis of PATH Study, Waves 1 and 2.
AB  - OBJECTIVES: We examine adolescent receipt of tobacco coupons and subsequent
      tobacco use. METHODS: Data were from the Population Assessment of Tobacco and
      Health (PATH) Study (2013-2015). We identified correlates of coupon receipt at
      Wave 1 (youth sample age 12-17 ; n = 13 651) including demographics, additional
      vulnerability factors that may place youth at risk of tobacco use and correlates
      of coupon receipt by channel. We examined associations of Wave 1 coupon receipt
      with Wave 2 tobacco use using weighted multivariable models. RESULTS: Overall,
      7.6% of US youth received tobacco coupons in the 6 months before Wave 1. Coupon
      recipients were more likely to be women, living outside urban areas, living with
      a tobacco user, current and former (vs never) tobacco users, having high
      internalising mental health symptoms and having a favourite tobacco
      advertisement. Coupons were received primarily through direct mail (56%), product
      packs (28%) and online (25%). Never tobacco users at Wave 1 who received coupons
      were more likely to be ever users at Wave 2 (adjusted OR (aOR)=1.42; 95% CI 1.06
      to 1.91). Coupon recipients were more likely to use a new tobacco product between
      waves (aOR=1.67; 95% CI 1.18 to 2.36) and report past 30-day tobacco use at Wave
      2 (aOR=1.81; 95% CI 1.31 to 2.49). CONCLUSIONS: One in 13 US youth (7.6%)
      received coupons. Vulnerable youth had the greatest odds of coupon receipt.
      Coupon recipients had greater odds of tobacco use among never users, trying a new
      tobacco product and current use. Coupon bans, limits on youth coupon exposure,
      stronger age verification, pack inserts or restricting coupon redemption may help
      reduce tobacco use among adolescents, particularly for those at greatest risk.

PMID- 29472445
TI  - Impact of tobacco control policies on smoking prevalence and quit ratios in 27
      European Union countries from 2006 to 2014.
AB  - BACKGROUND: Tobacco use is still highly prevalent in Europe, despite the tobacco
      control efforts made by the governments. The development of tobacco control
      policies varies substantially across countries. The Tobacco Control Scale (TCS)
      was introduced to quantify the implementation of tobacco control policies across
      European countries OBJECTIVE: To assess the midterm association of tobacco
      control policies on smoking prevalence and quit ratios among 27 European Union
      (EU) Member States (EU27). METHODS: Ecological study. We used the TCS in EU27 in
      2007 and the prevalence of tobacco and quit ratios data from the Eurobarometer
      survey (2006 (n=27 585) and 2014 (n=26 793)). We analysed the relationship
      between the TCS scores and smoking prevalence and quit ratios and their relative
      changes (between 2006 and 2014) by means of scatter plots and multiple linear
      regression models. RESULTS: In EU27, countries with higher scores in the TCS,
      which indicates higher tobacco control efforts, have lower prevalence of smokers,
      higher quit ratios and higher relative decreases in their prevalence rates of
      smokers over the last decade. The correlation between TCS scores and smoking
      prevalence (rsp=-0.444; P=0.02) and between the relative changes in smoking
      prevalence (rsp=-0.415; P=0.03) was negative. A positive correlation was observed
      between TCS scores and quit ratios (rsp=0.373; P=0.06). The percentage of smoking
      prevalence explained by all TCS components was 28.9%. CONCLUSION: EU27 should
      continue implementing comprehensive tobacco control policies as they are key for
      reducing the prevalence of smoking and an increase tobacco cessation rates in
      their population.

PMID- 29472446
TI  - Hematopoiesis by iPSC-derived hematopoietic stem cells of aplastic anemia that
      escape cytotoxic T-cell attack.
AB  - Hematopoietic stem cells (HSCs) that lack HLA-class I alleles as a result of copy
      number neutral loss of heterozygosity of the short arm of chromosome 6 (6pLOH) or
      HLA allelic mutations often constitute hematopoiesis in patients with acquired
      aplastic anemia (AA), but the precise mechanisms underlying clonal hematopoiesis
      induced by these HLA-lacking (HLA-) HSCs remain unknown. To address this issue,
      we generated induced pluripotent stem cells (iPSCs) from an AA patient who
      possessed HLA-B4002-lacking (B4002-) leukocytes. Three different iPSC clones
      (wild-type [WT], 6pLOH+, and B*40:02-mutant) were established from the patient's
      monocytes. Three-week cultures of the iPSCs in the presence of various growth
      factors produced hematopoietic cells that make up 50% to 70% of the CD34+ cells
      of each phenotype. When 106 iPSC-derived CD34+ (iCD34+) cells with the 3
      different genotypes were injected into the femoral bone of C57BL/6.Rag2 mice,
      2.1% to 7.3% human multilineage CD45+ cells of each HLA phenotype were detected
      in the bone marrow, spleen, and peripheral blood of the mice at 9 to 12 weeks
      after the injection, with no significant difference in the human:mouse chimerism
      ratio among the 3 groups. Stimulation of the patient's CD8+ T cells with the WT
      iCD34+ cells generated a cytotoxic T lymphocyte (CTL) line capable of killing WT
      iCD34+ cells but not B4002- iCD34+ cells. These data suggest that B4002- iCD34+
      cells show a repopulating ability similar to that of WT iCD34+ cells when
      autologous T cells are absent and CTL precursors capable of selectively killing
      WT HSCs are present in the patient's peripheral blood.

PMID- 29472447
TI  - Dock8 regulates BCR signaling and activation of memory B cells via WASP and CD19.
AB  - Dock8 deficiency leads to immunodeficiency, and the role of Dock8 in B-cell
      development and function has been revealed; however, the role of DocK8 on B-cell
      receptor (BCR) signaling and function of memory B cells remains elusive. In this
      study, we generated a Dock8 knockout mouse model and collected peripheral blood
      mononuclear cells from Dock8 patients to study the effect of Dock8 deficiency on
      the BCR signaling and activation of memory B cells with confocal microscopy and
      total internal reflection fluorescence microscopy. The activation of key,
      positive upstream BCR signaling molecules, pCD19 and phosphorylated Brutons
      tyrosine kinase (pBtk), is reduced. Interestingly, the total protein and
      activated levels of Wiskott-Aldrich syndrome protein (WASP) are decreased in
      Dock8-deficient mouse B cells. Our previous research has shown that WASP
      positively regulates cd19 transcription; furthermore, we found that Dock8
      regulates cd19 transcription. What we found in Dock8 patients can be a phenotype
      copied from Dock8 mice. The early activation of memory B cells from Dock8
      patients is disrupted with reduced BCR clustering, B-cell spreading, and
      signalosome recruitment into the degree of naive B cells, as well as the
      transition from naive B cells to unswitched memory B cells. Overall, our study
      provides a novel mechanism for Dock8 regulation of BCR signaling by regulating
      cd19 transcription, as well as the underlying mechanism of noncompetence of
      memory B cells in Dock8 patients.

PMID- 29472448
TI  - Double-stranded DNA break polarity skews repair pathway choice during
      intrachromosomal and interchromosomal recombination.
AB  - Activation-induced cytidine deaminase (AID) inflicts DNA damage at Ig genes to
      initiate class switch recombination (CSR) and chromosomal translocations.
      However, the DNA lesions formed during these processes retain an element of
      randomness, and thus knowledge of the relationship between specific DNA lesions
      and AID-mediated processes remains incomplete. To identify necessary and
      sufficient DNA lesions in CSR, the Cas9 endonuclease and nickase variants were
      used to program DNA lesions at a greater degree of predictability than is
      achievable with conventional induction of CSR. Here we show that Cas9-mediated
      nicks separated by up to 250 nucleotides on opposite strands can mediate CSR.
      Staggered double-stranded breaks (DSBs) result in more end resection and
      junctional microhomology than blunt DSBs. Moreover, Myc-Igh chromosomal
      translocations, which are carried out primarily by alternative end joining (A
      EJ), were preferentially induced by 5' DSBs. These data indicate that DSBs with
      5' overhangs skew intrachromosomal and interchromosomal end-joining toward A-EJ.
      In addition to lending potential insight to AID-mediated phenomena, this work has
      broader carryover implications in DNA repair and lymphomagenesis.

PMID- 29472450
TI  - Race to the native state.

PMID- 29472449
TI  - Nrf2 activation attenuates genetic endoplasmic reticulum stress induced by a
      mutation in the phosphomannomutase 2 gene in zebrafish.
AB  - Nrf2 plays critical roles in animals' defense against electrophiles and oxidative
      stress by orchestrating the induction of cytoprotective genes. We previously
      isolated the zebrafish mutant it768, which displays up-regulated expression of
      Nrf2 target genes in an uninduced state. In this paper, we determine that the
      gene responsible for it768 was the zebrafish homolog of phosphomannomutase 2
      (Pmm2), which is a key enzyme in the initial steps of N-glycosylation, and its
      mutation in humans leads to PMM2-CDG (congenital disorders of glycosylation), the
      most frequent type of CDG. The pmm2it768 larvae exhibited mild defects in N
      glycosylation, indicating that the pmm2it768 mutation is a hypomorph, as in human
      PMM2-CDG patients. A gene expression analysis showed that pmm2it768 larvae
      display up-regulation of endoplasmic reticulum (ER) stress, suggesting that the
      activation of Nrf2 was induced by the ER stress. Indeed, the treatment with the
      ER stress-inducing compounds up-regulated the gstp1 expression in an Nrf2
      dependent manner. Furthermore, the up-regulation of gstp1 by the pmm2
      inactivation was diminished by knocking down or out double-stranded RNA-activated
      protein kinase (PKR)-like ER kinase (PERK), one of the main ER stress sensors,
      suggesting that Nrf2 was activated in response to the ER stress via the PERK
      pathway. ER stress-induced activation of Nrf2 was reported previously, but the
      results have been controversial. Our present study clearly demonstrated that ER
      stress can indeed activate Nrf2 and this regulation is evolutionarily conserved
      among vertebrates. Moreover, ER stress induced in pmm2it768 mutants was
      ameliorated by the treatment of the Nrf2-activator sulforaphane, indicating that
      Nrf2 plays significant roles in the reduction of ER stress.

PMID- 29472451
TI  - Genetic manipulation of structural color in bacterial colonies.
AB  - Naturally occurring photonic structures are responsible for the bright and vivid
      coloration in a large variety of living organisms. Despite efforts to understand
      their biological functions, development, and complex optical response, little is
      known of the underlying genes involved in the development of these nanostructures
      in any domain of life. Here, we used Flavobacterium colonies as a model system to
      demonstrate that genes responsible for gliding motility, cell shape, the
      stringent response, and tRNA modification contribute to the optical appearance of
      the colony. By structural and optical analysis, we obtained a detailed
      correlation of how genetic modifications alter structural color in bacterial
      colonies. Understanding of genotype and phenotype relations in this system opens
      the way to genetic engineering of on-demand living optical materials, for use as
      paints and living sensors.

PMID- 29472452
TI  - Group size in social-ecological systems.
AB  - Cooperation becomes more difficult as a group becomes larger, but it is unclear
      where it will break down. Here, we study group size within well-functioning
      social-ecological systems. We consider centuries-old evidence from hundreds of
      communities in the Alps that harvested common property resources. Results show
      that the average group size remained remarkably stable over about six centuries,
      in contrast to a general increase in the regional population. The population more
      than doubled, but although single groups experienced fluctuations over time, the
      average group size remained stable. Ecological factors, such as managing forest
      instead of pasture land, played a minor role in determining group size. The
      evidence instead indicates that factors related to social interactions had a
      significant role in determining group size. We discuss possible interpretations
      of the findings based on constraints in individual cognition and obstacles in
      collective decision making.

PMID- 29472453
TI  - Comment on "The whole-soil carbon flux in response to warming".
AB  - In a compelling study, Hicks Pries et al (Reports, 31 March 2017, p. 1420) showed
      that 4 degrees C warming enhanced soil CO2 production in the 1-meter soil
      profile, with all soil depths displaying similar temperature sensitivity (Q10).
      We argue that some caveats can be identified in their experimental approach and
      analysis, and that these critically undermine their conclusions and hence their
      claim that the strength of feedback between the whole-soil carbon and climate has
      been underestimated in terrestrial models.

PMID- 29472454
TI  - Response to Comment on "The whole-soil carbon flux in response to warming".
AB  - Temperature records and model predictions demonstrate that deep soils warm at the
      same rate as surface soils, contrary to Xiao et al's assertions. In response to
      Xiao et al's critique of our Q10 analysis, we present the results with all data
      points included, which show Q10 values of >2 throughout the soil profile,
      indicating that all soil depths responded to warming.

PMID- 29472457
TI  - News at a glance.

PMID- 29472456
TI  - Science matters for the census.

PMID- 29472455
TI  - BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during
      apoptosis.
AB  - Mitochondrial apoptosis is mediated by BAK and BAX, two proteins that induce
      mitochondrial outer membrane permeabilization, leading to cytochrome c release
      and activation of apoptotic caspases. In the absence of active caspases,
      mitochondrial DNA (mtDNA) triggers the innate immune cGAS/STING pathway, causing
      dying cells to secrete type I interferon. How cGAS gains access to mtDNA remains
      unclear. We used live-cell lattice light-sheet microscopy to examine the
      mitochondrial network in mouse embryonic fibroblasts. We found that after BAK/BAX
      activation and cytochrome c loss, the mitochondrial network broke down and large
      BAK/BAX pores appeared in the outer membrane. These BAK/BAX macropores allowed
      the inner mitochondrial membrane to herniate into the cytosol, carrying with it
      mitochondrial matrix components, including the mitochondrial genome. Apoptotic
      caspases did not prevent herniation but dismantled the dying cell to suppress
      mtDNA-induced innate immune signaling.

PMID- 29472458
TI  - Europe's first artists were Neandertals.

PMID- 29472459
TI  - Worms living in your veins? Seventeen volunteers said 'OK'.

PMID- 29472461
TI  - Biologist unveils China's first private research university.

PMID- 29472460
TI  - Bringing an Iranian oasis back from the dead.

PMID- 29472462
TI  - Ocean array alters view of Atlantic conveyor.

PMID- 29472463
TI  - 'Extinct' Caribbeans have living descendants.

PMID- 29472464
TI  - Just add science.

PMID- 29472465
TI  - First up: Texas.

PMID- 29472466
TI  - Keeping watch on the ocean.

PMID- 29472467
TI  - Cancer detection: Seeking signals in blood.

PMID- 29472468
TI  - Unnaturally aglow with a bright inner light.

PMID- 29472469
TI  - Toward nitrogen-fixing plants.

PMID- 29472470
TI  - Boron compounds tackle dinitrogen.

PMID- 29472471
TI  - The Global Virome Project.

PMID- 29472472
TI  - Biocontrol of invasive carp: Risks abound.

PMID- 29472473
TI  - Waterbirds targeted in Iran's wetlands.

PMID- 29472474
TI  - Shifting sands could bring invasive species.

PMID- 29472475
TI  - The perfect postdoc.

PMID- 29472476
TI  - Soliton microcomb range measurement.
AB  - Laser-based range measurement systems are important in many application areas,
      including autonomous vehicles, robotics, manufacturing, formation flying of
      satellites, and basic science. Coherent laser ranging systems using dual
      frequency combs provide an unprecedented combination of long range, high
      precision, and fast update rate. We report dual-comb distance measurement using
      chip-based soliton microcombs. A single pump laser was used to generate dual
      frequency combs within a single microresonator as counterpropagating solitons. We
      demonstrated time-of-flight measurement with 200-nanometer precision at an
      averaging time of 500 milliseconds within a range ambiguity of 16 millimeters.
      Measurements at distances up to 25 meters with much lower precision were also
      performed. Our chip-based source is an important step toward miniature dual-comb
      laser ranging systems that are suitable for photonic integration.

PMID- 29472478
TI  - Infrared hyperbolic metasurface based on nanostructured van der Waals materials.
AB  - Metasurfaces with strongly anisotropic optical properties can support deep
      subwavelength-scale confined electromagnetic waves (polaritons), which promise
      opportunities for controlling light in photonic and optoelectronic applications.
      We developed a mid-infrared hyperbolic metasurface by nanostructuring a thin
      layer of hexagonal boron nitride that supports deep subwavelength-scale phonon
      polaritons that propagate with in-plane hyperbolic dispersion. By applying an
      infrared nanoimaging technique, we visualize the concave (anomalous) wavefronts
      of a diverging polariton beam, which represent a landmark feature of hyperbolic
      polaritons. The results illustrate how near-field microscopy can be applied to
      reveal the exotic wavefronts of polaritons in anisotropic materials and
      demonstrate that nanostructured van der Waals materials can form a highly
      variable and compact platform for hyperbolic infrared metasurface devices and
      circuits.

PMID- 29472477
TI  - Ultrafast optical ranging using microresonator soliton frequency combs.
AB  - Light detection and ranging is widely used in science and industry. Over the past
      decade, optical frequency combs were shown to offer advantages in optical
      ranging, enabling fast distance acquisition with high accuracy. Driven by
      emerging high-volume applications such as industrial sensing, drone navigation,
      or autonomous driving, there is now a growing demand for compact ranging systems.
      Here, we show that soliton Kerr comb generation in integrated silicon nitride
      microresonators provides a route to high-performance chip-scale ranging systems.
      We demonstrate dual-comb distance measurements with Allan deviations down to 12
      nanometers at averaging times of 13 microseconds along with ultrafast ranging at
      acquisition rates of 100 megahertz, allowing for in-flight sampling of gun
      projectiles moving at 150 meters per second. Combining integrated soliton-comb
      ranging systems with chip-scale nanophotonic phased arrays could enable compact
      ultrafast ranging systems for emerging mass applications.

PMID- 29472479
TI  - Nitrogen fixation and reduction at boron.
AB  - Currently, the only compounds known to support fixation and functionalization of
      dinitrogen (N2) under nonmatrix conditions are based on metals. Here we present
      the observation of N2 binding and reduction by a nonmetal, specifically a
      dicoordinate borylene. Depending on the reaction conditions under which potassium
      graphite is introduced as a reductant, N2 binding to two borylene units results
      in either neutral (B2N2) or dianionic ([B2N2]2-) products that can be
      interconverted by respective exposure to further reductant or to air. The 15N
      isotopologues of the neutral and dianionic molecules were prepared with 15N
      labeled dinitrogen, allowing observation of the nitrogen nuclei by 15N nuclear
      magnetic resonance spectroscopy. Protonation of the dianionic compound with
      distilled water furnishes a diradical product with a central hydrazido B2N2H2
      unit. All three products were characterized spectroscopically and
      crystallographically.

PMID- 29472480
TI  - Breakup of last glacial deep stratification in the South Pacific.
AB  - Stratification of the deep Southern Ocean during the Last Glacial Maximum is
      thought to have facilitated carbon storage and subsequent release during the
      deglaciation as stratification broke down, contributing to atmospheric CO2 rise.
      Here, we present neodymium isotope evidence from deep to abyssal waters in the
      South Pacific that confirms stratification of the deepwater column during the
      Last Glacial Maximum. The results indicate a glacial northward expansion of Ross
      Sea Bottom Water and a Southern Hemisphere climate trigger for the deglacial
      breakup of deep stratification. It highlights the important role of abyssal
      waters in sustaining a deep glacial carbon reservoir and Southern Hemisphere
      climate change as a prerequisite for the destabilization of the water column and
      hence the deglacial release of sequestered CO2 through upwelling.

PMID- 29472481
TI  - Tracking the global footprint of fisheries.
AB  - Although fishing is one of the most widespread activities by which humans harvest
      natural resources, its global footprint is poorly understood and has never been
      directly quantified. We processed 22 billion automatic identification system
      messages and tracked >70,000 industrial fishing vessels from 2012 to 2016,
      creating a global dynamic footprint of fishing effort with spatial and temporal
      resolution two to three orders of magnitude higher than for previous data sets.
      Our data show that industrial fishing occurs in >55% of ocean area and has a
      spatial extent more than four times that of agriculture. We find that global
      patterns of fishing have surprisingly low sensitivity to short-term economic and
      environmental variation and a strong response to cultural and political events
      such as holidays and closures.

PMID- 29472482
TI  - Coral reefs will transition to net dissolving before end of century.
AB  - Ocean acidification refers to the lowering of the ocean's pH due to the uptake of
      anthropogenic CO2 from the atmosphere. Coral reef calcification is expected to
      decrease as the oceans become more acidic. Dissolving calcium carbonate (CaCO3)
      sands could greatly exacerbate reef loss associated with reduced calcification
      but is presently poorly constrained. Here we show that CaCO3 dissolution in reef
      sediments across five globally distributed sites is negatively correlated with
      the aragonite saturation state (Omegaar) of overlying seawater and that CaCO3
      sediment dissolution is 10-fold more sensitive to ocean acidification than coral
      calcification. Consequently, reef sediments globally will transition from net
      precipitation to net dissolution when seawater Omegaar reaches 2.92 +/- 0.16
      (expected circa 2050 CE). Notably, some reefs are already experiencing net
      sediment dissolution.

PMID- 29472483
TI  - U-Th dating of carbonate crusts reveals Neandertal origin of Iberian cave art.
AB  - The extent and nature of symbolic behavior among Neandertals are obscure.
      Although evidence for Neandertal body ornamentation has been proposed, all cave
      painting has been attributed to modern humans. Here we present dating results for
      three sites in Spain that show that cave art emerged in Iberia substantially
      earlier than previously thought. Uranium-thorium (U-Th) dates on carbonate crusts
      overlying paintings provide minimum ages for a red linear motif in La Pasiega
      (Cantabria), a hand stencil in Maltravieso (Extremadura), and red-painted
      speleothems in Ardales (Andalucia). Collectively, these results show that cave
      art in Iberia is older than 64.8 thousand years (ka). This cave art is the
      earliest dated so far and predates, by at least 20 ka, the arrival of modern
      humans in Europe, which implies Neandertal authorship.

PMID- 29472485
TI  - Structural principles that enable oligomeric small heat-shock protein paralogs to
      evolve distinct functions.
AB  - Oligomeric proteins assemble with exceptional selectivity, even in the presence
      of closely related proteins, to perform their cellular roles. We show that most
      proteins related by gene duplication of an oligomeric ancestor have evolved to
      avoid hetero-oligomerization and that this correlates with their acquisition of
      distinct functions. We report how coassembly is avoided by two oligomeric small
      heat-shock protein paralogs. A hierarchy of assembly, involving intermediates
      that are populated only fleetingly at equilibrium, ensures selective
      oligomerization. Conformational flexibility at noninterfacial regions in the
      monomers prevents coassembly, allowing interfaces to remain largely conserved.
      Homomeric oligomers must overcome the entropic benefit of coassembly and,
      accordingly, homomeric paralogs comprise fewer subunits than homomers that have
      no paralogs.

PMID- 29472487
TI  - Independent but not alone.

PMID- 29472484
TI  - Patient-derived organoids model treatment response of metastatic gastrointestinal
      cancers.
AB  - Patient-derived organoids (PDOs) have recently emerged as robust preclinical
      models; however, their potential to predict clinical outcomes in patients has
      remained unclear. We report on a living biobank of PDOs from metastatic, heavily
      pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2
      clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree
      of similarity to the original patient tumors. Molecular profiling of tumor
      organoids was matched to drug-screening results, suggesting that PDOs could
      complement existing approaches in defining cancer vulnerabilities and improving
      treatment responses. We compared responses to anticancer agents ex vivo in
      organoids and PDO-based orthotopic mouse tumor xenograft models with the
      responses of the patients in clinical trials. Our data suggest that PDOs can
      recapitulate patient responses in the clinic and could be implemented in
      personalized medicine programs.

PMID- 29472486
TI  - Single-cell bioluminescence imaging of deep tissue in freely moving animals.
AB  - Bioluminescence is a natural light source based on luciferase catalysis of its
      substrate luciferin. We performed directed evolution on firefly luciferase using
      a red-shifted and highly deliverable luciferin analog to establish AkaBLI, an all
      engineered bioluminescence in vivo imaging system. AkaBLI produced emissions in
      vivo that were brighter by a factor of 100 to 1000 than conventional systems,
      allowing noninvasive visualization of single cells deep inside freely moving
      animals. Single tumorigenic cells trapped in the mouse lung vasculature could be
      visualized. In the mouse brain, genetic labeling with neural activity sensors
      allowed tracking of small clusters of hippocampal neurons activated by novel
      environments. In a marmoset, we recorded video-rate bioluminescence from neurons
      in the striatum, a deep brain area, for more than 1 year. AkaBLI is therefore a
      bioengineered light source to spur unprecedented scientific, medical, and
      industrial applications.

PMID- 29472489
TI  - Responses to mechanically and visually cued water waves in the nervous system of
      the medicinal leech.
AB  - Sensitivity to water waves is a key modality by which aquatic predators can
      detect and localize their prey. For one such predator - the medicinal leech,
      Hirudo verbana - behavioral responses to visual and mechanical cues from water
      waves are well documented. Here, we quantitatively characterized the response
      patterns of a multisensory interneuron, the S cell, to mechanically and visually
      cued water waves. As a function of frequency, the response profile of the S cell
      replicated key features of the behavioral prey localization profile in both
      visual and mechanical modalities. In terms of overall firing rate, the S cell
      response was not direction selective, and although the direction of spike
      propagation within the S cell system did follow the direction of wave propagation
      under certain circumstances, it is unlikely that downstream neuronal targets can
      use this information. Accordingly, we propose a role for the S cell in the
      detection of waves but not in the localization of their source. We demonstrated
      that neither the head brain nor the tail brain are required for the S cell to
      respond to visually cued water waves.

PMID- 29472490
TI  - RNA thermosensors: how might animals exploit their regulatory potential?
AB  - The secondary and tertiary orders of RNA structure are crucial for a suite of RNA
      related functions, including regulation of translation, gene expression and RNA
      turnover. The temperature sensitivity of RNA secondary and tertiary structures is
      exploited by bacteria to fabricate RNA thermosensing systems that allow a rapid
      adaptive response to temperature change. RNA thermometers (RNATs) present in non
      coding regions of certain mRNAs of pathogenic bacteria enable rapid upregulation
      of translation of virulence proteins when the temperature of the bacterium rises
      after entering a mammalian host. Rapid upregulation of translation of bacterial
      heat-shock proteins likewise is governed in part by RNATs. Turnover of mRNA may
      be regulated by temperature-sensitive RNA structures. Whereas the roles of
      temperature-sensitive RNA structures similar to RNATs in Eukarya and Archaea are
      largely unknown, there would appear to be a potential for all taxa to adaptively
      regulate their thermal physiology through exploitation of RNA-based thermosensory
      responses akin to those of bacteria. In animals, these responses might include
      regulation of translation of stress-induced proteins, alternative splicing of
      messenger RNA precursors, differential expression of allelic proteins, modulation
      of activities of small non-coding RNAs, regulation of mRNA turnover and control
      of RNA editing. New methods for predicting, detecting and experimentally
      modifying RNA secondary structure offer promising windows into these fascinating
      aspects of RNA biochemistry. Elucidating whether animals too have exploited the
      types of RNA thermosensing tools that are used so effectively by bacteria seems
      likely to provide exciting new insights into the mechanisms of evolutionary
      adaptation and acclimatization to temperature.

PMID- 29472491
TI  - Child Health Outcomes After Presumptive Infection Treatment in Pregnant Women: A
      Randomized Trial.
AB  - BACKGROUND AND OBJECTIVES: We showed earlier that presumptive infection treatment
      in pregnancy reduced the prevalence of neonatal stunting in a rural low-income
      setting. In this article, we assess how these gains were sustained and reflected
      in childhood growth, development, and mortality. METHODS: We enrolled 1320
      pregnant Malawian women in a randomized trial and treated them for malaria and
      other infections with either 2 doses of sulfadoxine-pyrimethamine (SP) (control),
      monthly SP, or monthly sulfadoxine-pyrimethamine and 2 doses of azithromycin (AZI
      SP). Child height or length and mortality were recorded at 1, 6, 12, 24, 36, 48,
      and 60 months and development at 60 months by using Griffith's Mental Development
      Scales. RESULTS: Throughout follow-up, the mean child length was 0.4 to 0.7 cm
      higher (P < .05 at 1-12 months), the prevalence of stunting was 6 to 11
      percentage points lower (P < .05 at 12-36 months), and the 5-year cumulative
      incidence of stunting was 13 percentage points lower (hazard ratio: 0.70, 95%
      confidence interval [CI]: 0.60 to 0.83, P < .001) in the AZI-SP group than in the
      control group. The mean developmental score was 3.8 points higher in the AZI-SP
      group than in the control group (95% CI: 1.1 to 6.4, P = .005). Total mortality
      during pregnancy and childhood was 15.3%, 15.1%, and 13.1% (P = .60) in the
      control, monthly SP, and AZI-SP groups, respectively. Postneonatal mortality
      (secondary outcome) was 5.5%, 3.3%, and 1.9%, respectively (risk ratio of AZI-SP
      versus control: 0.34, 95% CI: 0.15 to 0.76, P = .008). CONCLUSIONS: Provision of
      AZI-SP rather than 2 doses of SP during pregnancy reduced the incidence of
      stunting in childhood. AZI-SP during pregnancy also had a positive effect on
      child development and may have reduced postneonatal mortality.

PMID- 29472492
TI  - Angiomatoid Fibrous Histiocytoma With Paraneoplastic Platelet Storage Pool
      Deficiency.
AB  - Angiomatoid fibrous histiocytoma is a rare soft tissue tumor usually discovered
      in young individuals. This tumor is often mistaken for a hematoma and typically
      misdiagnosed. It is commonly found in the extremities and may be associated with
      a site of recent or previous trauma. Characteristic histology includes nodules of
      histiocytoid spindle cells with pseudoangiomatoid spaces, fibrous pseudocapsules,
      and lymphoid cuffing. We describe the case of an 8-year-old girl who presented
      after incision and drainage of a superficial thigh lesion and experienced
      subsequent chronic bleeding of her wound. Her initial presentation was concerning
      for an underlying bleeding disorder, and laboratory analysis uncovered a
      paraneoplastic platelet function disorder that resolved with therapy of the
      primary tumor.

PMID- 29472493
TI  - Variation in Anthropometric Status and Growth Failure in Low- and Middle-Income
      Countries.
AB  - BACKGROUND: Addressing anthropometric failure in low- and middle-income countries
      can have 2 targets of inference: addressing differences between individuals
      within populations (Wpop) or differences between populations (Bpop). We present a
      multilevel framework to apply both targets of inference simultaneously and
      quantify the extent to which variation in anthropometric status and growth
      failure is reflective of undernourished children or undernourished populations.
      METHODS: Cross-sectional data originated from the Demographic and Health Surveys
      program, covering children under age 5 from 57 countries surveyed between 2001
      and 2015. RESULTS: A majority of variation in child anthropometric status and
      growth failure was attributable to Wpop-associated differences, accounting for
      89%, 83%, and 85% of the variability in z scores for height for age, weight for
      age, and weight for height. Bpop-associated differences (communities, regions,
      and countries combined) were associated with 11%, 17%, and 15% of the variation
      in height-for-age z score, weight-for-age z score, and weight-for-height z score.
      Prevalence of anthropometric failure was closely correlated with mean levels of
      height and weight. Approximately 1% of Wpop variability, compared with 30% to 50%
      of the Bpop variability, was explained by mean values of maternal correlates of
      anthropometric status and failure. Although there is greater explanatory power
      Bpop, this varied because of modifiability of what constitutes population.
      CONCLUSIONS: Our results suggest that universal strategies to prevent future
      anthropometric failure in populations combined with targeted strategies to
      address both the impending and existing burden among children are needed.

PMID- 29472494
TI  - Disparities in Outcomes and Resource Use After Hospitalization for Cardiac
      Surgery by Neighborhood Income.
AB  - BACKGROUND: Significant disparities exist between patients of different races and
      with different family incomes; less is understood regarding community-level
      factors on outcomes. METHODS: In this study, we used linked data from the
      Pediatric Health Information System database and the US Census Bureau to examine
      associations between median annual household income by zip code and mortality,
      length of stay, inpatient standardized costs, and costs per day, over and above
      the effects of race and payer, first for children undergoing cardiac surgery
      (2005-2015) and then for all pediatric discharges (2012-2015). Median community
      level income was examined as continuous and categorical (by quartile) predictors.
      Hierarchical logistic and censored linear regression models were constructed. To
      these models, patient and surgical characteristics, year, race, payer, state,
      urban or rural designation, and center fixed effects were added. RESULTS: We
      identified 101 013 cardiac surgical (and 857 833 total) hospitalizations from 46
      institutions. Children from the lowest-income neighborhoods who were undergoing
      cardiac surgery had 1.18 times the odds of mortality (95% confidence interval
      [CI]: 1.03 to 1.35), 7% longer lengths of stay (CI: 1% to 14%), and 7% higher
      standardized costs (CI: 1% to 14%) than children from the highest-income
      neighborhoods. Results for all children were similar, both with and without any
      major chronic conditions. The effects of neighborhood were only partially
      explained by differences in race, payer, or the centers at which patients
      received care. There were no differences in costs per day. CONCLUSIONS: Children
      from lower-income neighborhoods are at increased risk of mortality and use more
      resource intensive care than children from higher-income communities, even after
      accounting for disparities between races, payers, and centers.

PMID- 29472495
TI  - Apixaban and Rosuvas--tatin Pharmacokinetics in Nonalcoholic Fatty Liver Disease.
AB  - There is little known about the impact of nonalcoholic fatty liver disease
      (NAFLD) on drug metabolism and transport. We examined the pharmacokinetics of
      oral apixaban (2.5 mg) and rosuvastatin (5 mg) when administered simultaneously
      in subjects with magnetic resonance imaging-confirmed NAFLD (N = 22) and healthy
      control subjects (N = 12). The area under the concentration-time curve to the
      last sampling time (AUC0-12) values for apixaban were not different between
      control and NAFLD subjects (671 and 545 ng/ml * hour, respectively; P = 0.15).
      Similarly, the AUC0-12 values for rosuvastatin did not differ between the control
      and NAFLD groups (25.4 and 20.1 ng/ml * hour, respectively; P = 0.28).
      Furthermore, hepatic fibrosis in NAFLD subjects was not associated with
      differences in apixaban or rosuvastatin pharmacokinetics. Decreased systemic
      exposures for both apixaban and rosuvastatin were associated with increased body
      weight (P < 0.001 and P < 0.05, respectively). In multivariable linear regression
      analyses, only participant weight but not NAFLD, age, or SLCO1B1/ABCG2/CYP3A5
      genotypes, was associated with apixaban and rosuvastatin AUC0-12 (P < 0.001 and P
      = 0.06, respectively). NAFLD does not appear to affect the pharmacokinetics of
      apixaban or rosuvastatin.

PMID- 29472496
TI  - IL-7-dependent maintenance of ILC3s is required for normal entry of lymphocytes
      into lymph nodes.
AB  - IL-7 is essential for the development and homeostasis of T and B lymphocytes and
      is critical for neonatal lymph node organogenesis because Il7-/- mice lack normal
      lymph nodes. Whether IL-7 is a continued requirement for normal lymph node
      structure and function is unknown. To address this, we ablated IL-7 function in
      normal adult hosts. Either inducible Il7 gene deletion or IL-7R blockade in
      adults resulted in a rapid loss of lymph node cellularity and a corresponding
      defect in lymphocyte entry into lymph nodes. Although stromal and dendritic cell
      components of lymph nodes were present in normal numbers and representation,
      innate lymphoid cell (ILC) subpopulations were substantially decreased after IL-7
      ablation. Testing lymphocyte homing in bone marrow chimeras reconstituted with
      Rorc-/- bone marrow confirmed that ILC3s in lymph nodes are required for normal
      lymphocyte homing. Collectively, our data suggest that maintenance of intact
      lymph nodes relies on IL-7-dependent maintenance of ILC3 cells.

PMID- 29472499
TI  - Brucella replicates in the ER.

PMID- 29472498
TI  - The bone marrow microenvironment in health and disease at a glance.
AB  - The bone marrow microenvironment (BMM) is the 'domicile' of hematopoietic stem
      cells, as well as of malignant processes that can develop there. Multiple and
      complex interactions with the BMM influence hematopoietic stem cell (HSC)
      physiology, but also the pathophysiology of hematological malignancies.
      Reciprocally, hematological malignancies alter the BMM, in order to render it
      more hospitable for malignant progression. In this Cell Science at a Glance
      article and accompanying poster, we highlight concepts of the normal and
      malignant hematopoietic stem cell niches. We present the intricacies of the BMM
      in malignancy and provide approaches for targeting the interactions between
      malignant cells and their BMM. This is done in an effort to augment existing
      treatment strategies in the future.

PMID- 29472500
TI  - The fly eye as a model system for centriole organization.

PMID- 29472501
TI  - Ca2+ and cation channels initiate cellular mechanosensation.

PMID- 29472502
TI  - Yeast septins join autophagy.

PMID- 29472497
TI  - ADAM17 is required for EGF-R-induced intestinal tumors via IL-6 trans-signaling.
AB  - Colorectal cancer is treated with antibodies blocking epidermal growth factor
      receptor (EGF-R), but therapeutic success is limited. EGF-R is stimulated by
      soluble ligands, which are derived from transmembrane precursors by ADAM17
      mediated proteolytic cleavage. In mouse intestinal cancer models in the absence
      of ADAM17, tumorigenesis was almost completely inhibited, and the few remaining
      tumors were of low-grade dysplasia. RNA sequencing analysis demonstrated down
      regulation of STAT3 and Wnt pathway components. Because EGF-R on myeloid cells,
      but not on intestinal epithelial cells, is required for intestinal cancer and
      because IL-6 is induced via EGF-R stimulation, we analyzed the role of IL-6
      signaling. Tumor formation was equally impaired in IL-6-/- mice and sgp130Fc
      transgenic mice, in which only trans-signaling via soluble IL-6R is abrogated.
      ADAM17 is needed for EGF-R-mediated induction of IL-6 synthesis, which via IL-6
      trans-signaling induces beta-catenin-dependent tumorigenesis. Our data reveal the
      possibility of a novel strategy for treatment of colorectal cancer that could
      circumvent intrinsic and acquired resistance to EGF-R blockade.

PMID- 29472503
TI  - Influences: Life lessons from Anita Zimmerman.

PMID- 29472504
TI  - Medical treatment is key in battling opioid crisis.

PMID- 29472505
TI  - New cancer therapies bring new types of adverse events.

PMID- 29472506
TI  - Recent FDA compounding guidances to pharmacies may not apply everywhere.

PMID- 29472507
TI  - Summaries of safety labeling changes approved by FDA-Boxed warnings highlights,
      October-December 2017.

PMID- 29472508
TI  - False prolongation of International Normalized Ratio associated with daptomycin.
AB  - PURPOSE: Persistent elevation of prothrombin time (PT) and International
      Normalized Ratio (INR) values in a patient receiving daptomycin is reported.
      SUMMARY: A morbidly obese 51-year-old man was hospitalized for evaluation for
      surgical intervention for gallstone pancreatitis and biliary obstruction.
      Previously prescribed warfarin therapy was withheld due to suspected coagulopathy
      and an elevated INR (5.1), and warfarin reversal was initiated. After undergoing
      partial cholecystectomy on hospital day 6, the patient developed sepsis and was
      treated with i.v. meropenem and daptomycin for vancomycin-resistant Enterococcus
      infection. Warfarin therapy, which had been resumed after cholecystectomy, was
      again discontinued on hospital day 12. On the eighth day of daptomycin therapy,
      the INR remained elevated (2.6) even though the patient had no warfarin exposure
      for 9 days. On hospital day 21, thromboelastography (TEG) indicated normal whole
      blood coagulation. Other anticoagulation markers normalized, but the INR remained
      elevated until daptomycin was discontinued. Daptomycin has been shown to falsely
      prolong the INR when specific laboratory reagents are used for PT and INR
      testing, but the specific reagent used in this case has not been previously
      implicated. CONCLUSION: Daptomycin therapy appeared to cause a false and
      substantial INR elevation in a patient who had been receiving warfarin. Results
      of TEG suggested that the INR elevation was an artifact of a drug-laboratory
      interaction and did not represent an anticoagulated state. The patient's INR
      normalized after linezolid was substituted for daptomycin.

PMID- 29472509
TI  - Association between continuous peripheral i.v. infusion of 3% sodium chloride
      injection and phlebitis in adults.
AB  - PURPOSE: One institution's experience with use of peripheral i.v. (PIV) catheters
      for prolonged infusions of 3% sodium chloride injection at rates up to 100 mL/hr
      is described. METHODS: A prospective, observational, 13-month quality assurance
      project was conducted at an academic medical center to evaluate frequencies of
      patient and catheter phlebitis among adult inpatients who received both an
      infusion of 3% sodium chloride injection for a period of >=4 hours through a
      dedicated PIV catheter and infusions of routine-care solutions (RCSs) through
      separate PIV catheters during the same hospital stay. RESULTS: Sixty patients
      received PIV infusions through a total of 291 catheters during the study period.
      The majority of patients (78%) received infusions of 3% sodium chloride injection
      for intracranial hypertension, with 30% receiving such infusions in the intensive
      care unit. Phlebitis occurred in 28 patients (47%) during infusions of 3% sodium
      chloride and 26 patients (43%) during RCS infusions (p = 0.19). Catheter
      phlebitis occurred in 73 catheters (25%), with no significant difference in the
      frequencies of catheter phlebitis with infusion of 3% sodium chloride versus RCSs
      (30% [32 of 106 catheters]) versus 22% [41 of 185 catheters]), p = 0.16).
      CONCLUSION: Patient and catheter phlebitis rates were not significantly different
      with infusions of 3% sodium chloride injection versus RCSs, suggesting that an
      osmolarity cutoff value of 900 mOsm/L for peripheral infusions of hypertonic
      saline solutions may not be warranted.

PMID- 29472510
TI  - Rates of depressive symptoms among pharmacy residents.
AB  - PURPOSE: Results of a survey-based study assessing rates of depression and
      depressive symptoms among pharmacy residents are reported. METHODS: In a time
      series study conducted during the 2015-16 residency year, pharmacy residents
      nationwide were invited to participate in a series of online surveys
      (administered in September and December 2015 and March 2016). Survey participants
      reported demographic data and provided information on residency characteristics
      and perceived family and program support; the survey incorporated the 9-item
      depression screening component of the Patient Health Questionnaire (PHQ-9).
      Descriptive statistics were used to estimate rates of depression and depressive
      symptoms. RESULTS: There were 633, 542, and 749 respondents to the September,
      December, and March surveys, respectively, for an overall response rate of 20.5%.
      The mean age of respondents was 26.9 years. Among respondents to the March
      survey, 39.9% (95% confidence interval, 36.2-43.2%) reported moderate-to-severe
      depressive symptoms. The rate of severe depressive symptoms (as measured by PHQ-9
      scores) increased from 3.2% in the September survey to 7.8% in the March survey
      (p < 0.05); rates of self-reported low depressive symptoms decreased over the
      same time period (p < 0.05). By comparison, rates of depressive symptoms in
      medical residents have been reported to be in the range of 30%. CONCLUSION: A
      survey of pharmacy residents found that the rate of depressive symptoms, as
      measured by the PHQ-9, was higher than reported rates in the U.S. general
      population.

PMID- 29472511
TI  - Development and implementation of an antimicrobial lock therapy guideline in a
      pediatric hospital.
AB  - PURPOSE: The development and implementation of an antimicrobial lock therapy
      guideline at a large pediatric hospital are described. SUMMARY: Central venous
      access devices (CVADs) are essential in the medical management of patients
      requiring long-term total parenteral nutrition, chemotherapy, or hemodialysis.
      However, the use of a CVAD carries a significant risk of the development of
      central line-associated bloodstream infection (CLABSI). Antimicrobial lock
      therapy is indicated for patients with CLABSIs who have no signs of exit site or
      tunnel infection and for whom catheter salvage is a goal. An antimicrobial lock
      therapy guideline was developed and implemented at a large pediatric hospital by
      an interprofessional team consisting of providers specializing in CVAD care.
      Development and implementation of the guideline included a needs assessment, a
      literature review, determination of patient selection criteria, addition of
      compounding formulations, development of administration techniques, and
      education. In all 10 instances of lock therapy in the 18 months after guideline
      implementation, the criteria for use were met; in 60% of those instances,
      patients received care from an infectious diseases physician. Each of the
      available lock solutions was used at least once during the 18-month period.
      CONCLUSION: Overall, implementation of a guideline on administration of
      antimicrobial lock therapy was successful. Nine patients received antimicrobial
      lock therapy in the 18 months after policy implementation; although 2 had their
      line removed (1 due to repeated line infections), neither required line
      replacement.

PMID- 29472512
TI  - Developing an electronic system to manage and track emergency medications.
AB  - PURPOSE: The development of a Web-based program to track and manage emergency
      medications with radio frequency identification (RFID) is described. SUMMARY: At
      the Cleveland Clinic, medication kit restocking records and dispense locations
      were historically documented using a paper record-keeping system. The Cleveland
      Clinic investigated options to replace the paper-based tracking logs with a Web
      based program that could track the real-time location and inventory of emergency
      medication kits. Vendor collaboration with a board of pharmacy (BOP) compliance
      inspector and pharmacy personnel resulted in the creation of a dual barcoding
      system using medication and pocket labels. The Web-based program was integrated
      with a Cleveland Clinic-developed asset tracking system using active RFID tags to
      give the real-time location of the medication kit. The Web-based program and the
      asset tracking system allowed identification of kits nearing expiration or
      containing recalled medications. Conversion from a paper-based system to a Web
      based program began in October 2013. After 119 days, data were evaluated to
      assess the success of the conversion. Pharmacists spent an average of 27 minutes
      per day approving medication kits during the postimplementation period versus 102
      minutes daily using the paper-based system, representing a 74% decrease in
      pharmacist time spent on this task. Prospective reports are generated monthly to
      allow the manager to assess the expected workload and adjust staffing for the
      next month. CONCLUSION: Implementation of a BOP-approved Web-based system for
      managing and tracking emergency medications with RFID integration decreased
      pharmacist review time, minimized compliance risk, and increased access to real
      time data.

PMID- 29472513
TI  - Stability of an extemporaneously compounded minoxidil oral suspension.
AB  - PURPOSE: Results of a study to determine the stability of an extemporaneously
      compounded minoxidil oral suspension under various temperature and stress
      conditions are reported. METHODS: Commercially available minoxidil tablets (10
      mg) were crushed to a fine powder, and predetermined amounts of 2 suspending
      vehicles were added to produce a 1-mg/mL suspension, which was stored in glass
      bottles at room temperature (25 +/- 2  degrees C) or in a refrigerator (4 +/- 2 
      degrees C). To simulate daily patient use, 5 days weekly 1 bottle of the
      suspension was removed from refrigerated storage and shaken and 0.5 mL of the
      contents discarded. At each specified time point, samples were analyzed in
      duplicate (n = 6 for each test condition) using a validated high-performance
      liquid chromatography method. Samples were visually observed and their pH
      measured at each time point. Microbiological studies were performed on day 0 and
      at week 24. RESULTS: The mean percentage of initial minoxidil concentration
      remaining in all refrigerated samples exceeded 90% throughout the 24-week study,
      with no change in appearance, pH, microbial activity, odor, or redispersibility.
      During storage at room temperature, the suspension exhibited a color change at
      week 4, with slight sedimentation after 6 weeks, although minoxidil recovery
      exceeded 90% for 10 weeks. CONCLUSION: An extemporaneously compounded minoxidil
      oral suspension was stable for 24 weeks when stored in a refrigerator. This
      suspension can be used for up to 3 weeks when stored at room temperature.

PMID- 29472514
TI  - Patient nonadherence to filling discharge medication prescriptions from the
      emergency department: Barriers and clinical implications.
AB  - PURPOSE: Barriers to and clinical implications of patient nonadherence to filling
      discharge medication prescriptions from the emergency department (ED) were
      evaluated. METHODS: This was a retrospective, observational analysis of patients
      discharged from the ED from April 2013 through May 2015 with medication
      prescriptions. Patients age 18-89 years who were seen in the ED and did not
      retrieve discharge medication prescriptions from the onsite, 24-hour ED discharge
      pharmacy were included in this study. Patients who did not pick up prescriptions
      were called and asked about barriers to prescription filling. These charts were
      then retrospectively reviewed and categorized. The primary study outcome was the
      frequency of nonadherence to filling discharge medications prescribed during the
      ED visit at the ED outpatient pharmacy. Secondary outcomes included identifying
      barriers to medication adherence, the rate of return ED visits within 30 days of
      ED discharge, and the rate of 30-day hospital admissions. Associations between
      patient and medication variables and the rates of return ED visits within 30 days
      of discharge and 30-day hospital admissions were analyzed. RESULTS: Of the 4,444
      patients discharged from the ED with a prescription to be filled at the satellite
      pharmacy, 510 were nonadherent. Of these patients, 505 had complete chart
      information available for evaluation. A large proportion of nonadherent patients
      revisited the ED within 30 days of ED discharge. Multivariate logistic regression
      found payer class, ethnicity, and sex were independently associated with return
      ED visits. CONCLUSION: The majority of patients who received a prescription
      during an ED visit filled their discharge medications. Sex, ethnicity, and payer
      class were independently associated with nonadherence.

PMID- 29472516
TI  - Summaries of safety labeling changes approved by FDA-Boxed warnings highlights,
      October-December 2017.

PMID- 29472515
TI  - Development of a standardized approach for managing opioids in adults with
      chronic noncancer pain.
AB  - PURPOSE: The implementation of a chronic pain protocol (CPP) and its effects on
      the management of long-term opioid therapy are described. SUMMARY: The CPP used
      at a federally qualified health center and primary care clinic was updated in
      2015 and included a prescribing ceiling in morphine equivalent dose (MED) per day
      and standardized the prescribing of chronic opioids. Intermittent urine drug
      screening performed at least once annually was added as a requirement of the pain
      management contract between the provider and the patient. An electronic report
      was developed to identify patients who were receiving long-term opioid therapy at
      the clinic. The clinical pharmacists identified patients from the report whose
      long-term opioid doses were over the clinic-recommended MED threshold, needed a
      pain contract, or were due for a urine drug screen. The number of patients for
      whom long-term opioids were prescribed decreased for all clinicians, including an
      88% reduction by nurse practitioners. Over 12 months, 97 fewer patients with
      chronic pain were treated with a long-term opioid at the clinic. The number of
      patients with pain contracts increased by 22.9% (p < 0.001), and the number of
      patients who had a urine drug screen over a 12-month period increased by 18.3% (p
      = 0.0016). CONCLUSION: The implementation of a CPP and the development of
      electronic reports to track provider adherence to the protocol led to a reduction
      in the number of chronic pain patients receiving long-term opioid therapy. The
      number of patients with pain contracts increased.

PMID- 29472517
TI  - Nordihydroguaiaretic Acid, a Lignan from Larrea tridentata (Creosote Bush),
      Protects Against American Lifestyle-Induced Obesity Syndrome Diet-Induced
      Metabolic Dysfunction in Mice.
AB  - To determine the effects of nordihydroguaiaretic acid (NDGA) on metabolic and
      molecular changes in response to feeding a typical American fast food or Western
      diet, mice were fed an American lifestyle-induced obesity syndrome (ALIOS) diet
      and subjected to metabolic analysis. Male C57BL/6J mice were randomly assigned to
      the ALIOS diet, the ALIOS diet supplemented with NDGA (NDGA+ALIOS), or a control
      diet and were maintained on the specific diet for 8 weeks. Mice fed the ALIOS
      diet showed increased body, liver, and epididymal fat pad weight as well as
      increased plasma alanine transaminase (ALT) and aspartate aminotransferase (AST)
      levels (a measure of liver injury) and liver triglyceride content.
      Coadministration of NDGA normalized body and epididymal fat pad weight, ALT and
      AST levels, and liver triglycerides. NDGA treatment also improved insulin
      sensitivity but not glucose intolerance in mice fed the ALIOS diet. In mice fed
      the NDGA+ALIOS diet, NDGA supplementation induced peroxisome proliferator
      activated receptor alpha (PPARalpha; the master regulator of fatty acid
      oxidation) and mRNA levels of carnitine palmitoyltransferases Cpt1c and Cpt2, key
      genes involved in fatty acid oxidation, compared with the ALIOS diet. NDGA
      significantly reduced liver endoplasmic reticulum (ER) stress response C/EBP
      homologous protein, compared with chow or the ALIOS diet, and also ameliorated
      ALIOS diet-induced elevation of apoptosis signaling protein, caspase 3. Likewise,
      NDGA downregulated the ALIOS diet-induced mRNA levels of Pparg, fatty acid
      synthase Fasn, and diacylglycerol acyltransferase Dgat2 NDGA treatment of ALIOS
      fed mice upregulated the hepatic expression of antioxidant enzymes, glutathione
      peroxidase 4, and peroxiredoxin 3 proteins. In conclusion, we provide evidence
      that NDGA improves metabolic dysregulation by simultaneously modulating the
      PPARalpha transcription factor and key genes involved in fatty acid oxidation,
      key antioxidant and lipogenic enzymes, and apoptosis and ER stress signaling
      pathways.

PMID- 29472519
TI  - Genetic Mosaicism and Cancer: Cause and Effect.
AB  - Increasing theoretical and experimental evidence suggests that the genomes of
      both normal and cancer cells are subject to continuous changes as a result of
      copying errors during replication, defects in chromosome segregation during
      mitosis, and direct chemical attacks by reactive oxygen species. The process of
      cellular genetic diversification begins during embryonic development and
      continues throughout life, leading to the phenomenon of somatic mosaicism. New
      information about the genetic diversity of cells composing the body makes us
      reconsider the existing concepts of cancer etiology and pathogenesis. Here, I
      suggest that a progressively deteriorating microenvironment ("soil") generates
      the cancerous "seed" and favors its development. Cancer Res; 78(6); 1375-8.
      (c)2018 AACR.

PMID- 29472518
TI  - Mass Spectrometry-Based Proteomics Reveals Potential Roles of NEK9 and MAP2K4 in
      Resistance to PI3K Inhibition in Triple-Negative Breast Cancers.
AB  - Activation of PI3K signaling is frequently observed in triple-negative breast
      cancer (TNBC), yet PI3K inhibitors have shown limited clinical activity. To
      investigate intrinsic and adaptive mechanisms of resistance, we analyzed a panel
      of patient-derived xenograft models of TNBC with varying responsiveness to
      buparlisib, a pan-PI3K inhibitor. In a subset of patient-derived xenografts,
      resistance was associated with incomplete inhibition of PI3K signaling and
      upregulated MAPK/MEK signaling in response to buparlisib. Outlier phosphoproteome
      and kinome analyses identified novel candidates functionally important to
      buparlisib resistance, including NEK9 and MAP2K4. Knockdown of NEK9 or MAP2K4
      reduced both baseline and feedback MAPK/MEK signaling and showed synthetic
      lethality with buparlisib in vitro A complex in/del frameshift in PIK3CA
      decreased sensitivity to buparlisib via NEK9/MAP2K4-dependent mechanisms. In
      summary, our study supports a role for NEK9 and MAP2K4 in mediating buparlisib
      resistance and demonstrates the value of unbiased omic analyses in uncovering
      resistance mechanisms to targeted therapy.Significance: Integrative
      phosphoproteogenomic analysis is used to determine intrinsic resistance
      mechanisms of triple-negative breast tumors to PI3K inhibition. Cancer Res;
      78(10); 2732-46. (c)2018 AACR.

PMID- 29472520
TI  - Trajectories of body mass index and waist circumference in four Peruvian settings
      at different level of urbanisation: the CRONICAS Cohort Study.
AB  - BACKGROUND: Studies have reported the incidence/risk of becoming obese, but few
      have described the trajectories of body mass index (BMI) and waist circumference
      (WC) over time, especially in low/middle-income countries. We assessed the
      trajectories of BMI and WC according to sex in four sites in Peru. METHODS: Data
      from the population-based CRONICAS Cohort Study were analysed. We fitted a
      population-averaged model by using generalised estimating equations. The outcomes
      of interest, with three data points over time, were BMI and WC. The exposure
      variable was the factorial interaction between time and study site. RESULTS: At
      baseline mean age was 55.7 years (SD: 12.7) and 51.6% were women. Mean follow-up
      time was 2.5 years (SD: 0.4). Over time and across sites, BMI and WC increased
      linearly. The less urbanised sites showed a faster increase than more urbanised
      sites, and this was also observed after sex stratification. Overall, the fastest
      increase was found for WC compared with BMI. Compared with Lima, the fastest
      increase in WC was in rural Puno (coefficient=0.73, P<0.001), followed by urban
      Puno (coefficient=0.59, P=0.001) and Tumbes (coefficient=0.22, P=0.088).
      CONCLUSIONS: There was a linear increase in BMI and WC across study sites, with
      the greatest increase in less urbanised areas. The ongoing urbanisation process,
      common to Peru and other low/middle-income countries, is accompanied by different
      trajectories of increasing obesity-related markers.

PMID- 29472521
TI  - Breast Metaplastic Squamous Cell Carcinoma Diagnosed with Fine Needle and Core
      Biopsy: A Case Study.
AB  - BACKGROUND Breast metaplastic squamous cell carcinoma (SCC) is a rare primary
      breast carcinoma, and overexpression of HER2 in this carcinoma is extremely
      uncommon. CASE REPORT We presented a case of a 48-year-old Asian female with
      breast metaplastic SCC. Fine needle aspiration biopsy (FNAB) and core needle
      biopsy (CNB) of the lesion were taken prior to surgical resection. FNAB smears
      demonstrated highly atypical squamous cells and a diagnosis positive for
      malignancy was rendered. CNB and a surgical resection specimen revealed invasive
      squamous carcinoma with keratin pearl formation and intercellular bridges.
      Further study demonstrated this was an unusual metaplastic SCC case with basal
      HER2 (+) phenotype. HER2 has been linked to poor prognosis and response to
      therapy. CONCLUSIONS The pathological diagnosis of the breast metaplastic SCC was
      made initially by FNAB and CNB. Identification of basal-HER2 (+) phenotype was
      critical for selection of hormonal therapies and chemotherapy.

PMID- 29472522
TI  - Finite Element Study of Implant Subsidence and Medial Tilt in Agility Ankle
      Replacement.
AB  - BACKGROUND Clinical studies indicate that in total ankle arthroplasty,
      postoperative implant subsidence and medial tilt become two significant concerns
      of the ankle replacement system, and which are associated with the contact
      between the bones and the talar component. Up to now, little attention has
      focused on the contact between the bones and the talar component. MATERIAL AND
      METHODS In order to address implant subsidence and medial tilt, one three
      dimensional finite element model of contact between the bone and the talar
      components was built with the material properties of the cancellous bone
      interpolated from the experimental data, which represents variation of material
      properties through the cancellous bones. The finite element model was used to
      study the following: variation of the Young's modulus of the bones, stiffness of
      the talar component, loading direction, and loading magnitude with the implant
      subsidence. RESULTS The computational results reveal that a variety of Young's
      modulus of the cancellous bones causes the medial tilting of the talar component
      and that big plastic strains are associated with tilting. The implant subsidence
      increases from 0.169 mm to 0.269 mm when the loading changes from 272 kg to 408
      kg. However, to the contrary, the implant subsidence decreases from 0.2676 mm to
      0.1783 mm when Young's modulus of the bones increases 50%. However, the implant
      subsidence shows little change with a different Young's modulus of the talar
      component from 88 GPa to 132 GPa. CONCLUSIONS Our study indicates that a variety
      of different Young's modulus of the cancellous bones cause the medial tilting of
      the talar component. To solve subsidence and tilting, both the contact area and
      the variation of material properties should be taken into account.

PMID- 29472523
TI  - Association of Graft Effluent Parameters with Donor Body Mass Index, Graft
      Quality, and Post-Transplant Events.
AB  - BACKGROUND We evaluated whether effluent parameters prior to reperfusion
      correlate with post-transplant outcomes in liver transplant recipients. MATERIAL
      AND METHODS Concentrations of high mobility group box 1 protein (HMGB1),
      uncleaved cytokeratin-18 (M65), caspase-cleaved cytokeratin 18 fragment (M30),
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl
      transpeptidase (GGT), and alkaline phosphatase (ALP) were measured in effluent
      samples from 53 adult liver recipients (42 survived for 1 year and 11 did not
      survive). RESULTS Effluent concentrations of ALP (p=0.006), AST (p=0.050), and
      Ca++ (p=0.003) were higher in patients with bacteriemia in the first post
      transplant year and ALP (p=0.015) was higher in patients with early graft
      dysfunction (EAD). Multivariate analysis of effluent parameters showed that Ca++
      >0.30 mmol/l (p=0.012, odds ratio [OR]=7.12, confidence interval [CI]=1.56
      32.58), and ALP >=27 IU/l (p=0.033, OR=5.31, CI=1.14-27.74) were significantly
      associated with 1-year post-transplant bacteriemia, whereas ALP >=27 IU/l
      (p=0.020, OR=5.56, CI=1.32-23.46) was significantly associated with EAD. HMGB1
      >54 pg/ml (p=0.008, OR=6.05, CI=1.59-23.00) was significantly associated with the
      donor body mass index (p=0.008, OR=6.05, CI=1.59-23.00) and fatty liver (p=0.005,
      OR=11.68, CI=2.10-64.01). CONCLUSIONS Effluent parameters are indicators of liver
      quality and predict the outcome of liver transplantation. High effluent Ca++ and
      ALP are risk factors of post-transplant bacteriemia. In addition, high ALP is a
      risk factor of EAD, and high HMGB1 is an indicator of liver quality.

PMID- 29472524
TI  - PU.1/microRNA-142-3p targets ATG5/ATG16L1 to inactivate autophagy and sensitize
      hepatocellular carcinoma cells to sorafenib.
AB  - Sorafenib is currently the only systemic agent approved for treatment of advanced
      hepatocellular carcinoma (HCC). However, intrinsic and acquired resistance to
      sorafenib remains a great challenge with respect to improving the prognoses of
      patients with HCC. The cyto-protective functions of autophagy have been suggested
      as a potential mechanism by which chemoresistance or targeted drug resistance
      occurs in tumour cells. In the present study, miR-142-3p was identified as a
      novel autophagy-regulating microRNA (miRNA) that plays a vital role in sorafenib
      resistance in HCC cells. Gain- and loss-of-function assays revealed that ectopic
      miR-142-3p upregulation sensitized HCC cells to sorafenib by reducing sorafenib
      induced autophagy, enhancing sorafenib-induced apoptosis and inhibiting cell
      growth, whereas miR-142-3p inhibition exerted contrasting effects. Bioinformatics
      analysis and luciferase reporter and rescue assays showed that autophagy-related
      5 (ATG5) and autophagy-related 16-like 1 (ATG16L1) are potential targets through
      which miR-142-3p regulates autophagy inhibition. Furthermore, we verified that
      PU.1 regulated the expression of miR-142-3p in conjunction with our cellular
      experiments and the related results in the literature. Our findings show that
      targeting the PU.1-miR-142-3p-ATG5/ATG16L1 axis may be a useful therapeutic
      strategy for preventing cyto-protective autophagy to overcome sorafenib
      resistance.

PMID- 29472525
TI  - Timescales of water accumulation in magmas and implications for short warning
      times of explosive eruptions.
AB  - Water plays a key role in magma genesis, differentiation, ascent and, finally,
      eruption. Despite the recognized crucial function of water, there are still
      several issues that continue to blur our view about its role in magmatic systems.
      What are the timescales of H2O accumulation in crystallizing magmas? What are the
      ascent rates of water-rich residual melts leading to explosive eruptions? Here,
      we track the timescale of water accumulation in a residual melt resulting from
      crystallization of a hydrous CO2-bearing magmatic mass stored at mid- to deep
      crustal levels in a subduction-related geodynamic setting. Our results indicate
      that, after a repose period ranging from few to several thousand years, water
      rich melts with water concentrations larger than 6-9 wt.% can migrate towards the
      Earth surface in very short timescales, on the order of days or even hours,
      possibly triggering explosive eruptions with short warning times and devoid of
      long-term geophysical precursors.

PMID- 29472526
TI  - Expanding frontiers in materials chemistry and physics with multiple anions.
AB  - During the last century, inorganic oxide compounds laid foundations for materials
      synthesis, characterization, and technology translation by adding new functions
      into devices previously dominated by main-group element semiconductor compounds.
      Today, compounds with multiple anions beyond the single-oxide ion, such as
      oxyhalides and oxyhydrides, offer a new materials platform from which superior
      functionality may arise. Here we review the recent progress, status, and future
      prospects and challenges facing the development and deployment of mixed-anion
      compounds, focusing mainly on oxide-derived materials. We devote attention to the
      crucial roles that multiple anions play during synthesis, characterization, and
      in the physical properties of these materials. We discuss the opportunities
      enabled by recent advances in synthetic approaches for design of both local and
      overall structure, state-of-the-art characterization techniques to distinguish
      unique structural and chemical states, and chemical/physical properties emerging
      from the synergy of multiple anions for catalysis, energy conversion, and
      electronic materials.

PMID- 29472528
TI  - Organellar stress intersects the astrocyte endoplasmic reticulum, mitochondria
      and nucleolus in HIV associated neurodegeneration.

PMID- 29472527
TI  - Hints on ATGL implications in cancer: beyond bioenergetic clues.
AB  - Among metabolic rearrangements occurring in cancer cells, lipid metabolism
      alteration has become a hallmark, aimed at sustaining accelerated proliferation.
      In particular, fatty acids (FAs) are dramatically required by cancer cells as
      signalling molecules and membrane building blocks, beyond bioenergetics. Along
      with de novo biosynthesis, free FAs derive from dietary sources or from
      intracellular lipid droplets, which represent the storage of triacylglycerols
      (TAGs). Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of
      lipolysis, catalysing the first step of intracellular TAGs hydrolysis in several
      tissues. However, the roles of ATGL in cancer are still neglected though a
      putative tumour suppressor function of ATGL has been envisaged, as its expression
      is frequently reduced in different human cancers (e.g., lung, muscle, and
      pancreas). In this review, we will introduce lipid metabolism focusing on ATGL
      functions and regulation in normal cell physiology providing also speculative
      perspectives on potential non-energetic functions of ATGL in cancer. In
      particular, we will discuss how ATGL is implicated, mainly through the peroxisome
      proliferator-activated receptor-alpha (PPAR-alpha) signalling, in inflammation,
      redox homoeostasis and autophagy, which are well-known processes deregulated
      during cancer formation and/or progression.

PMID- 29472529
TI  - A novel microRNA identified in hepatocellular carcinomas is responsive to LEF1
      and facilitates proliferation and epithelial-mesenchymal transition via targeting
      of NFIX.
AB  - Hepatocellular carcinoma (HCC) is one of the most prevalent cancers. It has been
      demonstrated that various cellular microRNAs (miRNAs) play an important role in
      HCC development. Here, we analyzed the miRNA profile in HCC tissues by Solexa
      sequencing, and we identified a novel microRNA, miR-HCC1, which is upregulated in
      HCC tissues. Further experiments showed that miR-HCC1 promoted HCC cell
      proliferation in vivo and in vitro, and migration and invasion resulting from the
      epithelial-mesenchymal transition (EMT) process. Nuclear factor I/X (NFIX), which
      inhibited cell proliferation, migration and invasion in HCC cells, was identified
      as a direct and functional target of miR-HCC1. Furthermore, lymphoid enhancer
      binding factor 1 (LEF1), a transcription factor, was shown to bind the promoter
      of miR-HCC1 and activate its expression. Collectively, these results indicate
      that LEF1-upregulated miR-HCC1 functions as an oncogene through the negative
      regulation of NFIX expression, which links the LEF1/miR-HCC1/NFIX axis to
      contribute to cell proliferation, migration and invasion of HCC cells and could
      provide novel insights into miRNA function and hepatocarcinogenesis and potential
      biomarkers for HCC.

PMID- 29472530
TI  - Histone deacetylase inhibitor ITF2357 leads to apoptosis and enhances doxorubicin
      cytotoxicity in preclinical models of human sarcoma.
AB  - Sarcomas are rare tumors with generally poor prognosis, for which current
      therapies have shown limited efficacy. Histone deacetylase inhibitors (HDACi) are
      emerging anti-tumor agents; however, little is known about their effect in
      sarcomas. By using established and patient-derived sarcoma cells with different
      subtypes, we showed that the pan-HDACi, ITF2357, potently inhibited in vitro
      survival in a p53-independent manner. ITF2357-mediated cell death implied the
      activation of mitochondrial apoptosis, as attested by induction of pro-apoptotic
      BH3-only proteins and a caspases-dependent mechanism. ITF2357 also induced
      autophagy, which protected sarcoma cells from apoptotic cell death. ITF2357
      activated forkhead box (FOXO) 1 and 3a transcription factors and their downstream
      target genes, however, silencing of both FOXO1 and 3a did not protect sarcoma
      cells against ITF2357-induced apoptosis and upregulated FOXO4 and 6. Notably,
      ITF2357 synergized with Doxorubicin to induce cell death of established and
      patient-derived sarcoma cells. Furthermore, combination treatment strongly
      impaired xenograft tumor growth in vivo, when compared to single treatments,
      suggesting that combination of ITF2357 with Doxorubicin has the potential to
      enhance sensitization in different preclinical models of sarcoma. Overall, our
      study highlights the therapeutic potential of ITF2357, alone or in rational
      combination therapies, for bone and soft tissue sarcomas management.

PMID- 29472531
TI  - Efficacy of the highly selective focal adhesion kinase inhibitor BI 853520 in
      adenocarcinoma xenograft models is linked to a mesenchymal tumor phenotype.
AB  - Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, has attracted
      interest as a target for pharmacological intervention in malignant diseases.
      Here, we describe BI 853520, a novel ATP-competitive inhibitor distinguished by
      high potency and selectivity. In vitro, the compound inhibits FAK
      autophosphorylation in PC-3 prostate carcinoma cells with an IC50 of 1 nmol/L and
      blocks anchorage-independent proliferation of PC-3 cells with an EC50 of 3
      nmol/L, whereas cells grown in conventional surface culture are 1000-fold less
      sensitive. In mice, the compound shows long half-life, high volume of
      distribution and high oral bioavailability; oral dosing of immunodeficient mice
      bearing subcutaneous PC-3 prostate adenocarcinoma xenografts resulted in rapid,
      long-lasting repression of FAK autophosphorylation in tumor tissue. Daily oral
      administration of BI 853520 to nude mice at doses of 50 mg/kg was well tolerated
      for prolonged periods of time. In a diverse panel of 16 subcutaneous
      adenocarcinoma xenograft models in nude mice, drug treatment resulted in a broad
      spectrum of outcomes, ranging from group median tumor growth inhibition values
      >100% and tumor regression in subsets of animals to complete lack of sensitivity.
      Biomarker analysis indicated that high sensitivity is linked to a mesenchymal
      tumor phenotype, initially defined by loss of E-cadherin expression and
      subsequently substantiated by gene set enrichment analysis. Further, we obtained
      microRNA expression profiles for 13 models and observed that hsa-miR-200c-3p
      expression is strongly correlated with efficacy (R2 = 0.889). BI 853520 is
      undergoing evaluation in early clinical trials.

PMID- 29472532
TI  - Co-inhibition of BET proteins and NF-kappaB as a potential therapy for colorectal
      cancer through synergistic inhibiting MYC and FOXM1 expressions.
AB  - The bromodomain and extra-terminal domain inhibitors (BETi) are promising
      epigenetic drugs for the treatment of various cancers through suppression of
      oncogenic transcription factors. However, only a subset of colorectal cancer
      (CRC) cells response to BETi. We investigate additional agents that could be
      combined with BETi to overcome this obstacle. JQ1-resistant CRC cells were used
      for screening of the effective combination therapies with JQ1. RNA-seq was
      performed to explore the mechanism of synergistic effect. The efficacy of
      combinational treatment was tested in the CRC cell line- and patient-derived
      xenograft (PDX) models. In BETi-sensitive CRC cells, JQ1 also impaired tumor
      angiogenesis through the c-myc/miR-17-92/CTGF+THBS1 axis. CTGF knockdown
      moderately counteracted anti-angiogenic effect of JQ1 and led to partially
      attenuated tumor regression. JQ1 decreased c-myc expression and NF-kappaB
      activity in BETi-sensitive CRC cells but not in resistant cells. Bortezomib
      synergistically sensitized BETi-resistant cells to the JQ1 treatment, and
      JQ1+Bortezomib induced G2/M arrest in CRC cells. Mechanistically, inhibition of
      NF-kappaB by Bortezomib or NF-kappaB inhibitor or IKK1/2 siRNA all rendered BETi
      resistant cells more sensitive to BETi by synergistic repression of c-myc, which
      in turn induces GADD45s' expression, and by synergistic repression of FOXM1 which
      in turn inhibit G2/M checkpoint genes' expression. Activation of NF-kappaB by
      IkappaBalpha siRNA induced resistance to JQ1 in BETi-sensitive CRC cells. Last,
      JQ1+Bortezomib inhibited tumor growth and angiogenesis in CRC cell line xenograft
      model and four PDX models. Our results indicate that anti-angiogenic effect of
      JQ1 plays a vital role in therapeutic effect of JQ1 in CRC, and provide a
      rationale for combined inhibition of BET proteins and NF-kappaB as a potential
      therapy for CRC.

PMID- 29472533
TI  - Input-output maps are strongly biased towards simple outputs.
AB  - Many systems in nature can be described using discrete input-output maps. Without
      knowing details about a map, there may seem to be no a priori reason to expect
      that a randomly chosen input would be more likely to generate one output over
      another. Here, by extending fundamental results from algorithmic information
      theory, we show instead that for many real-world maps, the a priori probability
      P(x) that randomly sampled inputs generate a particular output x decays
      exponentially with the approximate Kolmogorov complexity [Formula: see text] of
      that output. These input-output maps are biased towards simplicity. We derive an
      upper bound P(x) ? [Formula: see text], which is tight for most inputs. The
      constants a and b, as well as many properties of  P(x), can be predicted with
      minimal knowledge of the map. We explore this strong bias towards simple outputs
      in systems ranging from the folding of RNA secondary structures to systems of
      coupled ordinary differential equations to a stochastic financial trading model.

PMID- 29472534
TI  - Thermal influences on spontaneous rock dome exfoliation.
AB  - Rock domes, with their onion-skin layers of exfoliation sheets, are among the
      most captivating landforms on Earth. Long recognized as integral in shaping
      domes, the exact mechanism(s) by which exfoliation occurs remains enigmatic,
      mainly due to the lack of direct observations of natural events. In August 2014,
      during the hottest days of summer, a granitic dome in California, USA,
      spontaneously exfoliated; witnesses observed extensive cracking, including a
      ~8000 kg sheet popping into the air. Subsequent exfoliation episodes during the
      following two summers were recorded by instrumentation that captured-for the
      first time-exfoliation deformation and stress conditions. Here we show that
      thermal cycling and cumulative dome surface heating can induce subcritical
      cracking that culminates in seemingly spontaneous exfoliation. Our results
      indicate that thermal stresses-largely discounted in dome formation literature
      can play a key role in triggering exfoliation and therefore may be an important
      control for shaping domes worldwide.

PMID- 29472535
TI  - EGF receptor kinase suppresses ciliogenesis through activation of USP8
      deubiquitinase.
AB  - Ciliogenesis is generally inhibited in dividing cells, however, it has been
      unclear which signaling cascades regulate the phenomenon. Here, we report that
      epidermal growth factor receptor (EGFR) kinase suppresses ciliogenesis by
      directly phosphorylating the deubiquitinase USP8 on Tyr-717 and Tyr-810 in RPE1
      cells. These phosphorylations elevate the deubiquitinase activity, which then
      stabilizes the trichoplein-Aurora A pathway, an inhibitory mechanism of
      ciliogenesis. EGFR knockdown and serum starvation result in ciliogenesis through
      downregulation of the USP8-trichoplein-Aurora A signal. Moreover, primary cilia
      abrogation, which is induced upon IFT20 or Cep164 depletion, ameliorates the cell
      cycle arrest of EGFR knockdown cells. The present data reveal that the EGFR-USP8
      trichoplein-Aurora A axis is a critical signaling cascade that restricts
      ciliogenesis in dividing cells, and functions to facilitate cell proliferation.
      We further show that usp8 knockout zebrafish develops ciliopathy-related
      phenotypes including cystic kidney, suggesting that USP8 is a regulator of
      ciliogenesis in vertebrates.

PMID- 29472536
TI  - Spatial organization of bacterial populations in response to oxygen and carbon
      counter-gradients in pore networks.
AB  - Microbial activity in soil is spatially heterogeneous often forming spatial
      hotspots that contribute disproportionally to biogeochemical processes. Evidence
      suggests that bacterial spatial organization contributes to the persistence of
      anoxic hotspots even in unsaturated soils. Such processes are difficult to
      observe in situ at the microscale, hence mechanisms and time scales relevant for
      bacterial spatial organization remain largely qualitative. Here we develop an
      experimental platform based on glass-etched micrometric pore networks that mimics
      resource gradients postulated in soil aggregates to observe spatial organization
      of fluorescently tagged aerobic and facultative anaerobic bacteria. Two initially
      intermixed bacterial species, Pseudomonas putida and Pseudomonas veronii,
      segregate into preferential regions promoted by opposing gradients of carbon and
      oxygen (such persistent coexistence is not possible in well-mixed cultures). The
      study provides quantitative visualization and modeling of bacterial spatial
      organization within aggregate-like hotspots, a key step towards developing a
      mechanistic representation of bacterial community organization in soil pores.

PMID- 29472537
TI  - Programmed hierarchical patterning of bacterial populations.
AB  - Modern genetic tools allow the dissection and emulation of fundamental mechanisms
      shaping morphogenesis in multicellular organisms. Several synthetic genetic
      circuits for control of multicellular patterning have been reported to date.
      However, hierarchical induction of gene expression domains has received little
      attention from synthetic biologists, despite its importance in biological self
      organization. Here we report a synthetic genetic system implementing population
      based AND-logic for programmed autonomous induction of bacterial gene expression
      domains. We develop a ratiometric assay for bacteriophage T7 RNA polymerase
      activity and use it to systematically characterize different intact and split
      enzyme variants. We then utilize the best-performing variant to build a three
      color patterning system responsive to two different homoserine lactones. We
      validate the AND gate-like behavior of this system both in cell suspension and in
      surface culture. Finally, we use the synthetic circuit in a membrane-based
      spatial assay to demonstrate programmed hierarchical patterning of gene
      expression across bacterial populations.

PMID- 29472538
TI  - HDAC1 and HDAC2 integrate checkpoint kinase phosphorylation and cell fate through
      the phosphatase-2A subunit PR130.
AB  - Checkpoint kinases sense replicative stress to prevent DNA damage. Here we show
      that the histone deacetylases HDAC1/HDAC2 sustain the phosphorylation of the
      checkpoint kinases ATM, CHK1 and CHK2, activity of the cell cycle gatekeeper
      kinases WEE1 and CDK1, and induction of the tumour suppressor p53 in response to
      stalled DNA replication. Consequently, HDAC inhibition upon replicative stress
      promotes mitotic catastrophe. Mechanistically, HDAC1 and HDAC2 suppress the
      expression of PPP2R3A/PR130, a regulatory subunit of the trimeric
      serine/threonine phosphatase 2 (PP2A). Genetic elimination of PR130 reveals that
      PR130 promotes dephosphorylation of ATM by PP2A. Moreover, the ablation of PR130
      slows G1/S phase transition and increases the levels of phosphorylated CHK1,
      replication protein A foci and DNA damage upon replicative stress. Accordingly,
      stressed PR130 null cells are very susceptible to HDAC inhibition, which
      abrogates the S phase checkpoint, induces apoptosis and reduces the homologous
      recombination protein RAD51. Thus, PR130 controls cell fate decisions upon
      replicative stress.

PMID- 29472539
TI  - A regulatory circuit of two lncRNAs and a master regulator directs cell fate in
      yeast.
AB  - Transcription of long noncoding RNAs (lncRNAs) regulates local gene expression in
      eukaryotes. Many examples of how a single lncRNA controls the expression of an
      adjacent or nearby protein-coding gene have been described. Here we examine the
      regulation of a locus consisting of two contiguous lncRNAs and the master
      regulator for entry into yeast meiosis, IME1. We find that the cluster of two
      lncRNAs together with several transcription factors form a regulatory circuit by
      which IME1 controls its own promoter and thereby promotes its own expression.
      Inhibition or stimulation of this unusual feedback circuit affects timing and
      rate of IME1 accumulation, and hence the ability for cells to enter meiosis. Our
      data demonstrate that orchestrated transcription through two contiguous lncRNAs
      promotes local gene expression and determines a critical cell fate decision.

PMID- 29472540
TI  - Exploiting genetic variation to uncover rules of transcription factor binding and
      chromatin accessibility.
AB  - Single-nucleotide variants that underlie phenotypic variation can affect
      chromatin occupancy of transcription factors (TFs). To delineate determinants of
      in vivo TF binding and chromatin accessibility, we introduce an approach that
      compares ChIP-seq and DNase-seq data sets from genetically divergent murine
      erythroid cell lines. The impact of discriminatory single-nucleotide variants on
      TF ChIP signal enables definition at single base resolution of in vivo binding
      characteristics of nuclear factors GATA1, TAL1, and CTCF. We further develop a
      facile complementary approach to more deeply test the requirements of critical
      nucleotide positions for TF binding by combining CRISPR-Cas9-mediated mutagenesis
      with ChIP and targeted deep sequencing. Finally, we extend our analytical
      pipeline to identify nearby contextual DNA elements that modulate chromatin
      binding by these three TFs, and to define sequences that impact kb-scale
      chromatin accessibility. Combined, our approaches reveal insights into the
      genetic basis of TF occupancy and their interplay with chromatin features.

PMID- 29472542
TI  - Active colloids as mobile microelectrodes for unified label-free selective cargo
      transport.
AB  - Utilization of active colloids to transport both biological and inorganic cargo
      has been widely examined in the context of applications ranging from targeted
      drug delivery to sample analysis. In general, carriers are customized to load one
      specific target via a mechanism distinct from that driving the transport. Here we
      unify these tasks and extend loading capabilities to include on-demand selection
      of multiple nano/micro-sized targets without the need for pre-labelling or
      surface functionalization. An externally applied electric field is singularly
      used to drive the active cargo carrier and transform it into a mobile floating
      electrode that can attract (trap) or repel specific targets from its surface by
      dielectrophoresis, enabling dynamic control of target selection, loading and rate
      of transport via the electric field parameters. In the future, dynamic
      selectivity could be combined with directed motion to develop building blocks for
      bottom-up fabrication in applications such as additive manufacturing and soft
      robotics.

PMID- 29472541
TI  - Periosteum contains skeletal stem cells with high bone regenerative potential
      controlled by Periostin.
AB  - Bone regeneration relies on the activation of skeletal stem cells (SSCs) that
      still remain poorly characterized. Here, we show that periosteum contains SSCs
      with high bone regenerative potential compared to bone marrow stromal
      cells/skeletal stem cells (BMSCs) in mice. Although periosteal cells (PCs) and
      BMSCs are derived from a common embryonic mesenchymal lineage, postnatally PCs
      exhibit greater clonogenicity, growth and differentiation capacity than BMSCs.
      During bone repair, PCs can efficiently contribute to cartilage and bone, and
      integrate long-term after transplantation. Molecular profiling uncovers genes
      encoding Periostin and other extracellular matrix molecules associated with the
      enhanced response to injury of PCs. Periostin gene deletion impairs PC functions
      and fracture consolidation. Periostin-deficient periosteum cannot reconstitute a
      pool of PCs after injury demonstrating the presence of SSCs within periosteum and
      the requirement of Periostin in maintaining this pool. Overall our results
      highlight the importance of analyzing periosteum and PCs to understand bone
      phenotypes.

PMID- 29472544
TI  - Author Correction: Muscle pathology from stochastic low level DUX4 expression in
      an FSHD mouse model.
AB  - In the originally published version of this Article, an incorrect grant number,
      RO1 NS083549, was acknowledged. The correct grant number is RO1 AR055685. This
      error has now been corrected in both the PDF and HTML versions of the Article.

PMID- 29472543
TI  - DZNep inhibits H3K27me3 deposition and delays retinal degeneration in the rd1
      mice.
AB  - Retinitis pigmentosa (RP) is a group of inherited retinal degenerative diseases
      causing progressive loss of photoreceptors. Numerous gene mutations are
      identified to be related with RP, but epigenetic modifications may also be
      involved in the pathogenesis. Previous studies suggested that both DNA
      methylation and histone acetylation regulate photoreceptor cell death in RP mouse
      models. However, the role of histone methylation in RP has never been
      investigated. In this study, we found that trimethylation of several lysine sites
      of histone H3, including lysine 27 (H3K27me3), increased in the retinas of rd1
      mice. Histone methylation inhibitor DZNep significantly reduced the calpain
      activity, delayed the photoreceptor loss, and improved ERG response of rd1
      retina. RNA-sequencing indicated that DZNep synergistically acts on several
      molecular pathways that regulate photoreceptor survival in rd1 retina, including
      PI3K-Akt and photoreceptor differentiation pathways, revealing the therapeutic
      potential of DZNep for RP treatment. PI3K-Akt pathway and H3K27me3 form a
      feedback loop in rd1 retina, thus PI3K inhibitor LY294002 reduces phosphorylation
      of Ezh2 at serine 21 and enhances H3K27me3 deposition, and inhibiting H3K27me3 by
      DZNep can activate PI3K-Akt pathway by de-repressing gene expression of PI3K
      subunits Pik3r1 and Pik3r3. These findings suggest that histone methylation,
      especially H3K27me3 deposition is a novel mechanism and therapeutic target for
      retinal degenerative diseases, similar to H3K27me3-mediated ataxia-telangiectasia
      in Atm -/- mouse.

PMID- 29472545
TI  - Dynamic behavior of a rotary nanomotor in argon environments.
AB  - When argon is used as a protecting gas in the fabrication or working environment
      of a nanodevice, absorption of some argon atoms onto the surface of the device
      lead to different responses. In this work, the rotation of the rotor in a carbon
      nanotube (CNT)-based rotary nanomotor in argon environment is investigated. In
      the rotary nanomotor, two outer CNTs act as the stator and are used to constrain
      the inner CNT (i.e., the rotor). The rotor is driven to rotate by the stator due
      to their collision during thermal vibration of their atoms. A stable rotational
      frequency (SRF) of the rotor occurs when the rotor reaches a dynamic equilibrium
      state. The value of the SRF decreases exponentially with an increase in the
      initial argon density. At dynamic equilibrium date, some of the argon atoms
      rotate synchronously with the rotor when they are absorbed onto either internal
      or external surface of the rotor. The interaction between the rest of the argon
      atoms and the rotor is stronger at higher densities of argon, resulting in lower
      values of the SRF. These principles provide insight for future experimentation
      and fabrication of such rotary nanomotor.

PMID- 29472546
TI  - CXCR4 can induce PI3Kdelta inhibitor resistance in ABC DLBCL.

PMID- 29472547
TI  - FISSA: A neuropil decontamination toolbox for calcium imaging signals.
AB  - In vivo calcium imaging has become a method of choice to image neuronal
      population activity throughout the nervous system. These experiments generate
      large sequences of images. Their analysis is computationally intensive and
      typically involves motion correction, image segmentation into regions of interest
      (ROIs), and extraction of fluorescence traces from each ROI. Out of focus
      fluorescence from surrounding neuropil and other cells can strongly contaminate
      the signal assigned to a given ROI. In this study, we introduce the FISSA toolbox
      (Fast Image Signal Separation Analysis) for neuropil decontamination. Given pre
      defined ROIs, the FISSA toolbox automatically extracts the surrounding local
      neuropil and performs blind-source separation with non-negative matrix
      factorization. Using both simulated and in vivo data, we show that this toolbox
      performs similarly or better than existing published methods. FISSA requires only
      little RAM, and allows for fast processing of large datasets even on a standard
      laptop. The FISSA toolbox is available in Python, with an option for MATLAB
      format outputs, and can easily be integrated into existing workflows. It is
      available from Github and the standard Python repositories.

PMID- 29472548
TI  - Arginase-II activates mTORC1 through myosin-1b in vascular cell senescence and
      apoptosis.
AB  - Type-II L-arginine:ureahydrolase, arginase-II (Arg-II), is shown to activate
      mechanistic target of rapamycin complex 1 (mTORC1) pathway and contributes to
      cell senescence and apoptosis. In an attempt to elucidate the underlying
      mechanism, we identified myosin-1b (Myo1b) as a mediator. Overexpression of Arg
      II induces re-distribution of lysosome and mTOR but not of tuberous sclerosis
      complex (TSC) from perinuclear area to cell periphery, dissociation of TSC from
      lysosome and activation of mTORC1-ribosomal protein S6 kinase 1 (S6K1) pathway.
      Silencing Myo1b prevents all these alterations induced by Arg-II. By
      overexpressing Myo1b or its mutant with point mutation in its pleckstrin homology
      (PH) domain we further demonstrate that this effect of Myo1b is dependent on its
      PH domain that is required for Myo1b-lysosome association. Notably, Arg-II
      promotes association of Myo1b with lysosomes. In addition, we show that in
      senescent vascular smooth muscle cells with elevated endogenous Arg-II, silencing
      Myo1b prevents Arg-II-mediated lysosomal positioning, dissociation of TSC from
      lysosome, mTORC1 activation and cell apoptosis. Taken together, our study
      demonstrates that Myo1b mediates the effect of Arg-II in activating mTORC1-S6K1
      through promoting peripheral lysosomal positioning, that results in spatial
      separation and thus dissociation of TSC from lysosome, leading to hyperactive
      mTORC1-S6K1 signaling linking to cellular senescence/apoptosis.

PMID- 29472549
TI  - Directed gas phase formation of silicon dioxide and implications for the
      formation of interstellar silicates.
AB  - Interstellar silicates play a key role in star formation and in the origin of
      solar systems, but their synthetic routes have remained largely elusive so far.
      Here we demonstrate in a combined crossed molecular beam and computational study
      that silicon dioxide (SiO2) along with silicon monoxide (SiO) can be synthesized
      via the reaction of the silylidyne radical (SiH) with molecular oxygen (O2) under
      single collision conditions. This mechanism may provide a low-temperature path-in
      addition to high-temperature routes to silicon oxides in circumstellar envelopes
      possibly enabling the formation and growth of silicates in the interstellar
      medium necessary to offset the fast silicate destruction.

PMID- 29472550
TI  - PIM1 mediates epithelial-mesenchymal transition by targeting Smads and c-Myc in
      the nucleus and potentiates clear-cell renal-cell carcinoma oncogenesis.
AB  - Emerging evidence has shown that the PIM serine/threonine kinase family,
      including PIM1, PIM2 and PIM3, is associated with tumour progression towards
      metastasis. PIM1, an attractive molecular target, has been identified as a
      potential prognostic biomarker for haematological and epithelial malignancies.
      However, to date, the potential regulatory roles and molecular mechanisms by
      which PIM1 affects the development and progression of cancers, including clear
      cell renal-cell carcinoma (ccRCC), remain largely unknown. Herein, we present the
      first evidence that PIM1 is aberrantly overexpressed in human ccRCC tissues and
      cell lines and positively correlated with human ccRCC progression. In our study,
      depletion of PIM1 attenuated ccRCC cell proliferation, colony formation,
      migration, invasion and angiogenesis, suggesting that PIM1 expression may be a
      cancer-promoting event in ccRCC. Mechanistically, we observed that PIM1 could
      interact with Smad2 or Smad3 in the nucleus and subsequently phosphorylate Smad2
      and Smad3 to induce the expression of transcription factors, including ZEB1,
      ZEB2, Snail1, Snail2 and Twist, to promote epithelial-mesenchymal transition
      (EMT). In addition, PIM1-mediated phosphorylation of c-Myc activates the
      expression of the above transcription factors to synergistically promote EMT but
      does not activate Smads. Collectively, our results demonstrate that aberrant
      expression of PIM1 contributes to ccRCC development and progression. Moreover,
      our data reveal a potential molecular mechanism in which PIM1 mediates crosstalk
      between signalling pathways, including different Smad proteins and c-Myc, which
      target downstream transcription factors (ZEB1, ZEB2, Snail1, Snail2 and Twist) to
      trigger EMT. Together, our data suggest that PIM1 may be a potential therapeutic
      target for ccRCC patients.

PMID- 29472551
TI  - Enhancement of methane production from Cotton Stalk using different pretreatment
      techniques.
AB  - China produces large amount of cotton stalk (CS) residues as agricultural
      biomass, which are incinerated on-site, causing air pollution. The high organic
      content of CS could be utilized for biogas production, but the direct digestion
      without pretreatment always leads to a low methane yield and biodegradability,
      due to the complicated structure of lignocellulose. In order to search best
      fitting pretreatment methods in effective anaerobic digestion (AD) of CS, effects
      of various pretreatments including KOH, NaOH, Ca(OH)2, alkali hydrogen peroxide
      (AHP), H2SO4, H3PO4 and steam explosion (SE) were studied. It was seen that all
      treatments resulted in varying methane yields. Among all the pretreatments, acid
      pretreatment is not suitable for AD of CS. The results showed that the highest
      cumulative methane yield (CMY) of 192.4 mL.gVS-1 was obtained after 3% AHP
      pretreatment of CS, and the methane yield improved by 254.3% than the untreated
      CS. Therefore, AHP treatment was proven to be an efficient pretreatment
      technique. XRD and FTIR analyses had shown that pretreated CS had favorable
      structural changes. This research is beneficial in developing environment
      friendly and cost-effective pretreatment technologies to utilize CS for methane
      production in future application.

PMID- 29472552
TI  - Plasma ceramide levels are altered in low and normal birth weight men in response
      to short-term high-fat overfeeding.
AB  - Low birth weight (LBW) individuals have an increased risk of developing insulin
      resistance and type 2 diabetes compared with normal birth weight (NBW)
      individuals. We hypothesised that LBW individuals exhibit an increased fatty acid
      flux into lipogenesis in non-adipose tissue with a resulting accumulation of
      lipotoxic lipids, including ceramides, in the blood. Therefore, we measured
      fasting plasma levels of 27 ceramides in 18 young, healthy, LBW men and 25 NBW
      controls after an isocaloric control diet and a 5-day high-fat, high-calorie diet
      by HPLC-HRMS. LBW men did not show elevated plasma ceramide levels after the
      control or high-fat, high-calorie diet. An increased fatty acid oxidation rate in
      these individuals during both diets may limit ceramide synthesis and thereby
      compensate for a likely increased fatty acid load to non-adipose tissue.
      Interestingly, LBW and NBW men decreased d18:0-18:1/d18:1-18:0 and d18:1
      24:2/d18:2-24:1 levels and increased the d18:0-24:1a level in response to
      overfeeding. Plasma d18:0-24:1a and total ceramide levels were positively
      associated with the fasting blood glucose level and endogenous glucose production
      after the control diet, and the total ceramide level was in addition positively
      associated with hepatic insulin resistance. Further studies are needed to
      determine if lipotoxicity contributes to insulin resistance in LBW individuals.

PMID- 29472553
TI  - Systemic Homeostasis in Metabolome, Ionome, and Microbiome of Wild Yellowfin Goby
      in Estuarine Ecosystem.
AB  - Data-driven approaches were applied to investigate the temporal and spatial
      changes of 1,022 individuals of wild yellowfin goby and its potential interaction
      with the estuarine environment in Japan. Nuclear magnetic resonance (NMR)-based
      metabolomics revealed that growth stage is a primary factor affecting muscle
      metabolism. Then, the metabolic, elemental and microbial profiles of the pooled
      samples generated according to either the same habitat or sampling season as well
      as the river water and sediment samples from their habitats were measured using
      NMR spectra, inductively coupled plasma optical emission spectrometry and next
      generation 16 S rRNA gene sequencing. Hidden interactions in the integrated
      datasets such as the potential role of intestinal bacteria in the control of
      spawning migration, essential amino acids and fatty acids synthesis in wild
      yellowfin goby were further extracted using correlation clustering and market
      basket analysis-generated networks. Importantly, our systematic analysis of both
      the seasonal and latitudinal variations in metabolome, ionome and microbiome of
      wild yellowfin goby pointed out that the environmental factors such as the
      temperature play important roles in regulating the body homeostasis of wild fish.

PMID- 29472554
TI  - Reshaping the phonon energy landscape of nanocrystals inside a terahertz
      plasmonic nanocavity.
AB  - Phonons (quanta of collective vibrations) are a major source of energy
      dissipation and drive some of the most relevant properties of materials. In
      nanotechnology, phonons severely affect light emission and charge transport of
      nanodevices. While the phonon response is conventionally considered an inherent
      property of a nanomaterial, here we show that the dipole-active phonon resonance
      of semiconducting (CdS) nanocrystals can be drastically reshaped inside a
      terahertz plasmonic nanocavity, via the phonon strong coupling with the cavity
      vacuum electric field. Such quantum zero-point field can indeed reach extreme
      values in a plasmonic nanocavity, thanks to a mode volume well below lambda3/107.
      Through Raman measurements, we find that the nanocrystals within a nanocavity
      exhibit two new "hybridized" phonon peaks, whose spectral separation increases
      with the number of nanocrystals. Our findings open exciting perspectives for
      engineering the optical phonon response of functional nanomaterials and for
      implementing a novel platform for nanoscale quantum optomechanics.

PMID- 29472555
TI  - Detoxification of pulping black liquor with Pleurotus ostreatus or recombinant
      Pichia pastoris followed by CuO/TiO2/visible photocatalysis.
AB  - Cellulose-pulping requires chemicals such as Cl2, ClO2, H2O2, and O2. The black
      liquor (BL) generated exhibits a high chemical oxygen demand (COD), five-day
      biochemical oxygen demand (BOD5), and chlorophenol content, along with an
      augmented colour and increased pH. BL is often discharged into water bodies,
      where it has a negative impact on the environment. Towards that end, laccases are
      of great interest for bioremediation, since they can degrade aromatic and non
      aromatic compounds while reducing O2 to water instead of H2O2. As such, we
      evaluated Pleurotus ostreatus and Pichia pastoris (which produces rPOXA 1B
      laccase) in the treatment of synthetic BL (SBL) in an "in vitro" modified Kraft
      process followed by CuO/TiO2/visible light photocatalysis. Treating SBL with P.
      ostreatus viable biomass (VB) followed by CuO/TiO2/visible light photocatalysis
      resulted in 80.3% COD removal and 70.6% decolourisation. Toxic compounds such as
      2-methylphenol, 4-methylphenol, and 2-methoxyphenol were eliminated. Post-treated
      SBL exhibited low phytotoxicity, as evidenced by a Lactuca sativa L seed
      germination index (GI) > 50%. Likewise, SBL treatment with P. pastoris followed
      by VB/CuO/TiO2/visible light photocatalysis resulted in 63.7% COD removal and 46%
      decolourisation. Moreover, this treatment resulted in the elimination of most
      unwanted compounds, with the exception of 4-chlorophenol. The Lactuca sativa L
      seed GI of the post-treated SBL was 40%, indicating moderate phytotoxicity.

PMID- 29472556
TI  - Author Correction: Tropical explosive volcanic eruptions can trigger El Nino by
      cooling tropical Africa.
AB  - The original version of this Article omitted a reference to previous work in
      'Mann, M.E., Cane, M.A., Zebiak, S.E., Clement, A., Volcanic and Solar Forcing of
      the Tropical Pacific Over the Past 1000 Years, J. Climate 18, 447-456 (2005)'.
      This has been added as reference 62 at the end of the fourth sentence of the
      fourth paragraph of the Introduction: 'Early studies using simple coupled ocean
      atmosphere models26 proposed that following volcano-induced surface cooling,
      upwelling in the eastern equatorial Pacific acting on a reduced vertical
      temperature contrast between the ocean surface and interior leads to anomalous
      warming in this region, thereby favouring El Nino development the following
      year12, 27, 62.' This has been corrected in the PDF and HTML versions of the
      Article.

PMID- 29472557
TI  - Metformin exerts multitarget antileukemia activity in JAK2V617F-positive
      myeloproliferative neoplasms.
AB  - The recurrent gain-of-function JAK2V617F mutation confers growth factor
      independent proliferation for hematopoietic cells and is a major contributor to
      the pathogenesis of myeloproliferative neoplasms (MPN). The lack of complete
      response in most patients treated with the JAK1/2 inhibitor ruxolitinib indicates
      the need for identifying novel therapeutic strategies. Metformin is a biguanide
      that exerts selective antineoplastic activity in hematological malignancies. In
      the present study, we investigate and compare effects of metformin and
      ruxolitinib alone and in combination on cell signaling and cellular functions in
      JAK2V617F-positive cells. In JAK2V617F-expressing cell lines, metformin treatment
      significantly reduced cell viability, cell proliferation, clonogenicity, and
      cellular oxygen consumption and delayed cell cycle progression. Metformin reduced
      cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation.
      Metformin plus ruxolitinib demonstrated more intense reduction of cell viability
      and induction of apoptosis compared to monotherapy. Notably, metformin reduced
      Ba/F3 JAK2V617F tumor burden and splenomegaly in Jak2V617F knock-in-induced MPN
      mice and spontaneous erythroid colony formation in primary cells from
      polycythemia vera patients. In conclusion, metformin exerts multitarget
      antileukemia activity in MPN: downregulation of JAK2/STAT signaling and
      mitochondrial activity. Our exploratory study establishes novel molecular
      mechanisms of metformin and ruxolitinib action and provides insights for
      development of alternative/complementary therapeutic strategies for MPN.

PMID- 29472558
TI  - Kinetics of lithium peroxide oxidation by redox mediators and consequences for
      the lithium-oxygen cell.
AB  - Lithium-oxygen cells, in which lithium peroxide forms in solution rather than on
      the electrode surface, can sustain relatively high cycling rates but require
      redox mediators to charge. The mediators are oxidised at the electrode surface
      and then oxidise lithium peroxide stored in the cathode. The kinetics of lithium
      peroxide oxidation has received almost no attention and yet is crucial for the
      operation of the lithium-oxygen cell. It is essential that the molecules oxidise
      lithium peroxide sufficiently rapidly to sustain fast charging. Here, we
      investigate the kinetics of lithium peroxide oxidation by several different
      classes of redox mediators. We show that the reaction is not a simple outer
      sphere electron transfer and that the steric structure of the mediator molecule
      plays an important role. The fastest mediator studied could sustain a charging
      current of up to 1.9 A cm-2, based on a model for a porous electrode described
      here.

PMID- 29472559
TI  - Publisher Correction: Direct quantum process tomography via measuring sequential
      weak values of incompatible observables.
AB  - In the original version of this Article, the penultimate sentence of the second
      paragraph of the "Schematic and theory" section of the Results originally
      incorrectly read as "For instance, choosing thetaA = pi/4, 0, -pi/8 and pi/8
      rotates the bases |0>, |1>, |+>, and |-> into |1>, thereby implementing the
      observableA=|0><0|, |1><1|, |+><+| and, respectively." In the corrected version,
      "|-><-|" has been added before ", respectively". This error has been corrected in
      both the PDF and HTML versions of the Article.

PMID- 29472560
TI  - Landscape topography structures the soil microbiome in arctic polygonal tundra.
AB  - In the Arctic, environmental factors governing microbial degradation of soil
      carbon (C) in active layer and permafrost are poorly understood. Here we
      determined the functional potential of soil microbiomes horizontally and
      vertically across a cryoperturbed polygonal landscape in Alaska. With comparative
      metagenomics, genome binning of novel microbes, and gas flux measurements we show
      that microbial greenhouse gas (GHG) production is strongly correlated to
      landscape topography. Active layer and permafrost harbor contrasting microbiomes,
      with increasing amounts of Actinobacteria correlating with decreasing soil C in
      permafrost. While microbial functions such as fermentation and methanogenesis
      were dominant in wetter polygons, in drier polygons genes for C mineralization
      and CH4 oxidation were abundant. The active layer microbiome was poised to
      assimilate N and not to release N2O, reflecting low N2O flux measurements. These
      results provide mechanistic links of microbial metabolism to GHG fluxes that are
      needed for the refinement of model predictions.

PMID- 29472561
TI  - Human mitochondrial pyruvate carrier 2 as an autonomous membrane transporter.
AB  - The active transport of glycolytic pyruvate across the inner mitochondrial
      membrane is thought to involve two mitochondrial pyruvate carrier subunits, MPC1
      and MPC2, assembled as a 150 kDa heterotypic oligomer. Here, the recombinant
      production of human MPC through a co-expression strategy is first described;
      however, substantial complex formation was not observed, and predominantly
      individual subunits were purified. In contrast to MPC1, which co-purifies with a
      host chaperone, we demonstrated that MPC2 homo-oligomers promote efficient
      pyruvate transport into proteoliposomes. The derived functional requirements and
      kinetic features of MPC2 resemble those previously demonstrated for MPC in the
      literature. Distinctly, chemical inhibition of transport is observed only for a
      thiazolidinedione derivative. The autonomous transport role for MPC2 is validated
      in cells when the ectopic expression of human MPC2 in yeast lacking endogenous
      MPC stimulated growth and increased oxygen consumption. Multiple oligomeric
      species of MPC2 across mitochondrial isolates, purified protein and artificial
      lipid bilayers suggest functional high-order complexes. Significant changes in
      the secondary structure content of MPC2, as probed by synchrotron radiation
      circular dichroism, further supports the interaction between the protein and
      ligands. Our results provide the initial framework for the independent role of
      MPC2 in homeostasis and diseases related to dysregulated pyruvate metabolism.

PMID- 29472562
TI  - Galphai-mediated TRPC4 activation by polycystin-1 contributes to endothelial
      function via STAT1 activation.
AB  - Hypertension and aneurysm are frequently associated with autosomal dominant
      polycystic kidney disease (ADPKD) caused by polycystin-1 (PC1) mutations, which
      is closely related to endothelial dysfunction. PC1 is an atypical G-protein
      coupled receptor that activates G-proteins by self-cleavage; currently, however,
      the molecular and cellular mechanisms of the associated intracellular signaling
      and ion channel activation remain poorly elucidated. Here, we report an
      activation mechanism of a calcium-permeable canonical transient receptor
      potential 4 (TRPC4) channel by PC1 and its endothelial function. We found that
      the inhibitory Galphai3 protein selectively bound to the G-protein-binding domain
      on the C-terminus of PC1. The dissociation of Galphai3 upon cleavage of PC1
      increased TRPC4 activity. Calcium influx through TRPC4 activated the
      transcription factor STAT1 to regulate cell proliferation and death. The down
      regulation of PC1/TRPC4/STAT1 disrupted migration of endothelial cell monolayers,
      leading to an increase in endothelial permeability. These findings contribute to
      greater understanding of the high risk of aneurysm in patients with ADPKD.

PMID- 29472563
TI  - Non-Invasive Radiofrequency Field Treatment of 4T1 Breast Tumors Induces T-cell
      Dependent Inflammatory Response.
AB  - Previous work using non-invasive radiofrequency field treatment (RFT) in cancer
      has demonstrated its therapeutic potential as it can increase intratumoral blood
      perfusion, localization of intravenously delivered drugs, and promote a
      hyperthermic intratumoral state. Despite the well-known immunologic benefits that
      febrile hyperthermia can induce, an investigation of how RFT could modulate the
      intra-tumoral immune microenvironment had not been studied. Thus, using an
      established 4T1 breast cancer model in immune competent mice, we demonstrate that
      RFT induces a transient, localized, and T-cell dependent intratumoral
      inflammatory response. More specifically we show that multi- and singlet-dose RFT
      promote an increase in tumor volume in immune competent Balb/c mice, which does
      not occur in athymic nude models. Further leukocyte subset analysis at 24, 48,
      and 120 hours after a single RFT show a rapid increase in tumoral trafficking of
      CD4+ and CD8+ T-cells 24 hours post-treatment. Additional serum cytokine analysis
      reveals an increase in numerous pro-inflammatory cytokines and chemokines
      associated with enhanced T-cell trafficking. Overall, these data demonstrate that
      non-invasive RFT could be an effective immunomodulatory strategy in solid tumors,
      especially for enhancing the tumoral trafficking of lymphocytes, which is
      currently a major hindrance of numerous cancer immunotherapeutic strategies.

PMID- 29472564
TI  - Inhibitory modulation of cytochrome c oxidase activity with specific near
      infrared light wavelengths attenuates brain ischemia/reperfusion injury.
AB  - The interaction of light with biological tissue has been successfully utilized
      for multiple therapeutic purposes. Previous studies have suggested that near
      infrared light (NIR) enhances the activity of mitochondria by increasing
      cytochrome c oxidase (COX) activity, which we confirmed for 810 nm NIR. In
      contrast, scanning the NIR spectrum between 700 nm and 1000 nm revealed two NIR
      wavelengths (750 nm and 950 nm) that reduced the activity of isolated COX. COX
      inhibitory wavelengths reduced mitochondrial respiration, reduced the
      mitochondrial membrane potential (DeltaPsim), attenuated mitochondrial superoxide
      production, and attenuated neuronal death following oxygen glucose deprivation,
      whereas NIR that activates COX provided no benefit. We evaluated COX-inhibitory
      NIR as a potential therapy for cerebral reperfusion injury using a rat model of
      global brain ischemia. Untreated animals demonstrated an 86% loss of neurons in
      the CA1 hippocampus post-reperfusion whereas inhibitory NIR groups were robustly
      protected, with neuronal loss ranging from 11% to 35%. Moreover, neurologic
      function, assessed by radial arm maze performance, was preserved at control
      levels in rats treated with a combination of both COX-inhibitory NIR wavelengths.
      Taken together, our data suggest that COX-inhibitory NIR may be a viable non
      pharmacologic and noninvasive therapy for the treatment of cerebral reperfusion
      injury.

PMID- 29472566
TI  - Wetter summers can intensify departures from natural variability in a warming
      climate.
AB  - Climate change can drive local climates outside the range of their historical
      year-to-year variability, straining the adaptive capacity of ecological and human
      communities. We demonstrate that dependencies between climate variables can
      produce larger and earlier departures from natural variability than is detectable
      in individual variables. Using the example of summer temperature (Tx) and
      precipitation (Pr), we show that this departure intensification effect occurs
      when the bivariate climate change trajectory is misaligned with the dominant mode
      of joint historical variability. Departure intensification is evident in all six
      CMIP5 models that we examined: 23% (9-34%) of the global land area of each model
      exhibits a pronounced increase in 2sigma anomalies in the Tx-Pr regime relative
      to Tx or Pr alone. Observational data suggest that summer Tx-Pr correlations in
      distinct regions on all continents are sufficient to produce departure
      intensification. Precipitation can be an important driver of multivariate climate
      change signals relative to natural variability, despite typically having a much
      weaker univariate signal than temperature.

PMID- 29472565
TI  - Endogenous insensitivity to the Orco agonist VUAA1 reveals novel olfactory
      receptor complex properties in the specialist fly Mayetiola destructor.
AB  - Insect olfactory receptors are routinely expressed in heterologous systems for
      functional characterisation. It was recently discovered that the essential
      olfactory receptor co-receptor (Orco) of the Hessian fly, Mayetiola destructor
      (Mdes), does not respond to the agonist VUAA1, which activates Orco in all other
      insects analysed to date. Here, using a mutagenesis-based approach we identified
      three residues in MdesOrco, located in different transmembrane helices as
      supported by 3D modelling, that confer sensitivity to VUAA1. Reciprocal mutations
      in Drosophila melanogaster (Dmel) and the noctuid moth Agrotis segetum (Aseg)
      Orcos diminish sensitivity of these proteins to VUAA1. Additionally, mutating
      these residues in DmelOrco and AsegOrco compromised odourant receptor (OR)
      dependent ligand-induced Orco activation. In contrast, both wild-type and VUAA1
      sensitive MdesOrco were capable of forming functional receptor complexes when
      coupled to ORs from all three species, suggesting unique complex properties in M.
      destructor, and that not all olfactory receptor complexes are "created" equal.

PMID- 29472567
TI  - Polyrotaxane-based supramolecular theranostics.
AB  - The development of smart theranostic systems with favourable biocompatibility,
      high loading efficiency, excellent circulation stability, potent anti-tumour
      activity, and multimodal diagnostic functionalities is of importance for future
      clinical application. The premature burst release and poor degradation kinetics
      indicative of polymer-based nanomedicines remain the major obstacles for clinical
      translation. Herein we prepare theranostic shell-crosslinked nanoparticles
      (SCNPs) using a beta-cyclodextrin-based polyrotaxane (PDI-PCL-b-PEG-RGD?beta-CD
      NH2) to avoid premature drug leakage and achieve precisely controllable release,
      enhancing the maximum tolerated dose of the supramolecular nanomedicines. cRGDfK
      and perylene diimide are chosen as the stoppers of PDI-PCL-b-PEG-RGD?beta-CD-NH2,
      endowing the resultant SCNPs with excellent integrin targeting ability,
      photothermal effect, and photoacoustic capability. In vivo anti-tumour studies
      demonstrate that drug-loaded SCNPs completely eliminate the subcutaneous tumours
      without recurrence after a single-dose injection combining chemotherapy and
      photothermal therapy. These supramolecular nanomedicines also exhibit excellent
      anti-tumour performance against orthotopic breast cancer and prevent lung
      metastasis with negligible systemic toxicity.

PMID- 29472568
TI  - Lack of galectin-3 modifies differentially Notch ligands in bone marrow and
      spleen stromal cells interfering with B cell differentiation.
AB  - Galectin-3 (Gal-3) is a beta-galactoside binding protein that controls cell-cell
      and cell-extracellular matrix interactions. In lymphoid organs, gal-3 inhibits B
      cell differentiation by mechanisms poorly understood. The B cell development is
      dependent on tissue organization and stromal cell signaling, including IL-7 and
      Notch pathways. Here, we investigate possible mechanisms that gal-3 interferes
      during B lymphocyte differentiation in the bone marrow (BM) and spleen. The BM of
      gal-3-deficient mice (Lgals3-/- mice) was evidenced by elevated numbers of
      B220+CD19+c-Kit+IL-7R+ progenitor B cells. In parallel, CD45- bone marrow stromal
      cells expressed high levels of mRNA IL-7, Notch ligands (Jagged-1 and Delta-like
      4), and transcription factors (Hes-1, Hey-1, Hey-2 and Hey-L). The spleen of
      Lgals3-/- mice was hallmarked by marginal zone disorganization, high number of
      IgM+IgD+ B cells and CD138+ plasma cells, overexpression of Notch ligands (Jagged
      1, Delta-like 1 and Delta-like 4) by stromal cells and Hey-1. Morever, IgM+IgD+ B
      cells and B220+CD138+ CXCR4+ plasmablasts were significantly increased in the BM
      and blood of Lgals3-/- mice. For the first time, we demonstrated that gal-3
      inhibits Notch signaling activation in lymphoid organs regulating earlier and
      terminal events of B cell differentiation.

PMID- 29472570
TI  - The Po Delta is restarting progradation: geomorphological evolution based on a 47
      years Earth Observation dataset.
AB  - From the 1950s, the Po delta, one of the largest anthropogenic world deltas, has
      been subjected to a fast degradation and shoreline retreat due a marked reduction
      of sediment supply, mainly controlled by human impacts/factors, including
      subsidence. Through the interpretation of satellite images, coupled with the
      analysis of the flow discharge, and of the annual frequency of marine storms, we
      show that recently (>2010) the Po River has resumed delta progradation,
      especially in its northern portion. This happens after decades of erosion,
      followed by alternating regrowth and degradation phases, indicating conditions of
      substantial stability (1970-2000). Today the delta shows aggradation of new mouth
      bars at the main distributary mouth, a clear evidence of active constructive
      processes. The ongoing trend marks a countertendency compared to many deltas
      worldwide.

PMID- 29472569
TI  - Cysteine residues are essential for dimerization of Hippo pathway components
      YAP2L and TAZ.
AB  - Hippo signalling pathway is an emerging signalling pathway that plays important
      roles in organ size control, tumorigenesis, metastasis, stress response,
      apoptosis, stem cell differentiation and renewal during development and tissue
      homeostasis. Recent studies reported that human serine/threonine protein kinase,
      Mst1, a core component of the Hippo pathway can be activated through formation of
      homodimer. However, it is still unclear whether or not other components of the
      Hippo pathway are also regulated through dimerization. Here we provide the first
      evidence that Hippo components and oncoprotein YAP2L and TAZ can form homodimer
      in vitro and in vivo by forming disulphide bond through cysteine residue(s). We
      have also shown that the homodimers of YAP2L/TAZ are more stable and showed more
      oncogenic behaviour than their corresponding monomers as revealed by colony
      formation and cell transformation assay. Since cysteine post-translational
      regulation plays important roles in redox signalling, tumorigenesis and drug
      resistance, further studies on the functional effect of this dimerization through
      post-translational modulation of cysteine residues in YAP2L/TAZ will provide a
      significant contribution to our understanding of the roles of YAP2L/TAZ in cancer
      development and therapy.

PMID- 29472571
TI  - Serum profile changes in postpartum women with a history of childhood
      maltreatment: a combined metabolite and lipid fingerprinting study.
AB  - Childhood maltreatment (CM) can increase the risk of adverse health consequences
      in adulthood. A deeper insight in underlying biological pathways would be of high
      clinical relevance for early detection and intervention. The untargeted
      investigation of all detectable metabolites and lipids in biological samples
      represents a promising new avenue to identify so far unknown biological pathways
      associated with CM. Using an untargeted approach, liquid chromatography-mass
      spectrometry (LC-MS) was performed on peripheral blood serum samples collected
      three months postpartum from 105 women with varying degrees of CM exposure.
      Comprehensive univariate and multivariate statistical analyses consistently
      identified eight biomarker candidates putatively belonging to antioxidant-, lipid
      , and endocannabinoid-associated pathways, which differentiated between women
      with and without CM. Classification algorithms allowed for clear prediction of
      the CM status with high accuracy scores (~80-90%). Similar results were obtained
      when excluding all women with a lifetime psychiatric diagnosis. In order to
      confirm the identities of these promising biomarker candidates, LC-MS/MS analysis
      was applied, confirming one of the metabolites as bilirubin IXa, a potent
      antioxidant with immunomodulatory properties. In sum, our results suggest novel
      pathways that could explain long-term effects of CM on health and disease by
      influencing biological patterns associated with energy metabolism, inflammation,
      and oxidative stress.

PMID- 29472572
TI  - Onset and Evolution of Southern Annular Mode-Like Changes at Centennial
      Timescale.
AB  - The Southern Westerly Winds (SWW) are the surface expression of geostrophic winds
      that encircle the southern mid-latitudes. In conjunction with the Southern Ocean,
      they establish a coupled system that not only controls climate in the southern
      third of the world, but is also closely connected to the position of the
      Intertropical Convergence Zone and CO2 degassing from the deep ocean.
      Paradoxically, little is known about their behavior since the last ice age and
      relationships with mid-latitude glacier history and tropical climate variability.
      Here we present a lake sediment record from Chilean Patagonia (51 degrees S) that
      reveals fluctuations of the low-level SWW at mid-latitudes, including strong
      westerlies during the Antarctic Cold Reversal, anomalously low intensity during
      the early Holocene, which was unfavorable for glacier growth, and strong SWW
      since ~7.5 ka. We detect nine positive Southern Annular Mode-like events at
      centennial timescale since ~5.8 ka that alternate with cold/wet intervals
      favorable for glacier expansions (Neoglaciations) in southern Patagonia. The
      correspondence of key features of mid-latitude atmospheric circulation with
      shifts in tropical climate since ~10 ka suggests that coherent climatic shifts in
      these regions have driven climate change in vast sectors of the Southern
      Hemisphere at centennial and millennial timescales.

PMID- 29472573
TI  - Optimization of ClpXP activity and protein synthesis in an E. coli extract-based
      cell-free expression system.
AB  - Protein degradation is a fundamental process in all living cells and is essential
      to remove both damaged proteins and intact proteins that are no longer needed by
      the cell. We are interested in creating synthetic genetic circuits that function
      in a cell-free expression system. This will require not only an efficient protein
      expression platform but also a robust protein degradation system in cell extract.
      Therefore, we purified and tested the activity of E. coli ClpXP protease in cell
      free transcription-translation (TX-TL) systems that used E. coli S30 cell
      extract. Surprisingly, our studies showed that purified ClpXP added to the TX-TL
      system has very low proteolytic activity. The low activity of ClpXP was
      correlated with the rapid consumption of adenosine triphosphate (ATP) in cell
      extract. We improved the activity of ClpXP in cell extract by adding exogenous
      ATP and an energy regeneration system. We then established conditions for both
      protein synthesis, and protein degradation by ClpXP to occur simultaneously in
      the TX-TL systems. The optimized conditions for ClpXP activity will be useful for
      creating tunable synthetic genetic circuits and in vitro synthetic biology.

PMID- 29472574
TI  - Equal-Spin Andreev Reflection on Junctions of Spin-Resolved Quantum Hall Bulk
      State and Spin-Singlet Superconductor.
AB  - The recent development of superconducting spintronics has revealed the spin
      triplet superconducting proximity effect from a spin-singlet superconductor into
      a spin-polarized normal metal. In addition recently superconducting junctions
      using semiconductors are in demand for highly controlled experiments to engineer
      topological superconductivity. Here we report experimental observation of Andreev
      reflection in junctions of spin-resolved quantum Hall (QH) states in an InAs
      quantum well and the spin-singlet superconductor NbTi. The measured conductance
      indicates a sub-gap feature and two peaks on the outer side of the sub-gap
      feature in the QH plateau-transition regime increases. The observed structures
      can be explained by considering transport with Andreev reflection from two
      channels, one originating from equal-spin Andreev reflection intermediated by
      spin-flip processes and second arising from normal Andreev reflection. This
      result indicates the possibility to induce the superconducting proximity gap in
      the the QH bulk state, and the possibility for the development of superconducting
      spintronics in semiconductor devices.

PMID- 29472575
TI  - Glial cell type-specific changes in spinal dipeptidyl peptidase 4 expression and
      effects of its inhibitors in inflammatory and neuropatic pain.
AB  - Altered pain sensations such as hyperalgesia and allodynia are characteristic
      features of various pain states, and remain difficult to treat. We have shown
      previously that spinal application of dipeptidyl peptidase 4 (DPP4) inhibitors
      induces strong antihyperalgesic effect during inflammatory pain. In this study we
      observed low level of DPP4 mRNA in the rat spinal dorsal horn in physiological
      conditions, which did not change significantly either in carrageenan-induced
      inflammatory or partial nerve ligation-generated neuropathic states. In naive
      animals, microglia and astrocytes expressed DPP4 protein with one and two orders
      of magnitude higher than neurons, respectively. DPP4 significantly increased in
      astrocytes during inflammation and in microglia in neuropathy. Intrathecal
      application of two DPP4 inhibitors tripeptide isoleucin-prolin-isoleucin (IPI)
      and the antidiabetic drug vildagliptin resulted in robust opioid-dependent
      antihyperalgesic effect during inflammation, and milder but significant opioid
      independent antihyperalgesic action in the neuropathic model. The opioid-mediated
      antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors,
      while vildagliptin affected mainly delta-receptor activity, although mu- and
      kappa-receptors were also involved. None of the inhibitors influenced allodynia.
      Our results suggest pathology and glia-type specific changes of DPP4 activity in
      the spinal cord, which contribute to the development and maintenance of
      hyperalgesia and interact with endogenous opioid systems.

PMID- 29472576
TI  - Broad blocking of MDR efflux pumps by acetylshikonin and
      acetoxyisovalerylshikonin to generate hypersensitive phenotype of malignant
      carcinoma cells.
AB  - Cytotoxic activities of acetylshikonin and acetoxyisovalerylshikonin alone and in
      combination with chemotherapeutic agents against parental and drug resistant cell
      lines were determined using the MTT assay. Effects of Shikonin derivatives on
      BCRP, MDR1 and MRP transcript and protein levels were relatively measured.
      Finally, accumulation and efflux kinetics were conducted. The results revealed
      cell- and concentration-dependency of the cell cytotoxicity. Acetylshikonin and
      acetoxyisovalerylshikonin transiently made the mRNA ocean turbulent, but FACS
      analyses using fluorescent-labeled antibodies showed no significant change in the
      MDR-protein levels. Functional kinetics revealed significant block of MDR1, BCRP
      and MRP transporter in the presence of shikonin derivatives. Maximum accumulation
      fold changes was quantified to be 4.4 and consequently, acetoxyisovalerylshikonin
      pretreated EPG85.257RDB cells was chemosensitized to daunorubicin tension 3.1
      fold. Although, the MDR blockage was reported to follow time- and cell-dependent
      patterns, MDR1, BCRP and MRP2 responses to the shikonins are concentration
      independent. These data suggest uncompetitive transporter blockage behavior of
      these agents. The results indicated that shikonin derivatives stimulate uptake
      and reduce efflux of chemotherapeutic agents in the malignant cancer cells,
      suggesting that chemotherapy in combination with shikonin compounds may be
      beneficial to cancer cells that overexpress multidrug resistance transporters.

PMID- 29472577
TI  - Design and Demonstration of Impedance-matched Dual-band Chiral Metasurfaces.
AB  - We propose a new family of impedance-matched chiral metasurfaces that offer
      arbitrary polarization control at two different frequencies. To this end, two
      main problems are addressed: (1) determination of the required surface impedances
      for a certain user-defined chiral functionality at two frequencies and (2) their
      physical realization at microwaves. The first milestone is achieved through a
      proposed synthesis method that combines a semi-analytical method and a nonlinear
      optimization technique. In particular, the impedances are computed such that the
      devised chiral metasurface is also impedance-matched to a terminating medium. The
      chiral metasurfaces are then physically realized at microwaves by cascading
      layers of rotated arrays of multiple concentric rectangular copper rings. We
      establish that these proposed unit cells offer distinct dual-resonances that can
      be arbitrarily and independently tuned for two orthogonal linear polarizations at
      each of the two operating frequencies. This allows simultaneous physical mapping
      of the required surface impedances at two frequencies. The versatility and
      generality of the proposed numerical and physical solutions are demonstrated
      through two design examples: A dual-band circular polarization selective surface
      (CPSS) and a dual-band polarization rotator (PR). The dual-band CPSS is further
      confirmed experimentally at 20 GHz and 30 GHz based on a free-space quasi-optical
      system.

PMID- 29472578
TI  - The assassin bug Pristhesancus plagipennis produces two distinct venoms in
      separate gland lumens.
AB  - The assassin bug venom system plays diverse roles in prey capture, defence and
      extra-oral digestion, but it is poorly characterised, partly due to its
      anatomical complexity. Here we demonstrate that this complexity results from
      numerous adaptations that enable assassin bugs to modulate the composition of
      their venom in a context-dependent manner. Gland reconstructions from multimodal
      imaging reveal three distinct venom gland lumens: the anterior main gland (AMG);
      posterior main gland (PMG); and accessory gland (AG). Transcriptomic and
      proteomic experiments demonstrate that the AMG and PMG produce and accumulate
      distinct sets of venom proteins and peptides. PMG venom, which can be elicited by
      electrostimulation, potently paralyses and kills prey insects. In contrast, AMG
      venom elicited by harassment does not paralyse prey insects, suggesting a
      defensive role. Our data suggest that assassin bugs produce offensive and
      defensive venoms in anatomically distinct glands, an evolutionary adaptation
      that, to our knowledge, has not been described for any other venomous animal.

PMID- 29472580
TI  - Changes in micro-relief during different water erosive stages of purple soil
      under simulated rainfall.
AB  - This study investigated the variation characteristics of micro-topography during
      successive erosive stages of water erosion: splash erosion (SpE), sheet erosion
      (ShE), and rill erosion (RE). Micro-topography was quantified using surface
      elevation change, soil roughness (SR) and multifractal model. Results showed that
      the area of soil surface elevation decay increased gradually with the development
      of water erosion. With rainfall, the combined effects of the detachment by
      raindrop impact and the transport of runoff decreased SR, whereas rill erosion
      contributed to increase SR. With the increase in slope gradient, soil erosion
      area gradually decreased at the splash erosion stage. By contrast, soil erosion
      area initially decreased and then increased at the sheet and rill erosion stages.
      The width of the D q spectra (DeltaD) values increased at the splash erosion
      stage and then decreased at the sheet and rill erosion stages on the 10 degrees 
      slope, opposite to that on the 15 degrees  slope. The DeltaD values decreased
      with the evolution of water erosive stages on the 20 degrees  slope. The slope
      had an enhancing effect on the evolution of water erosion. In this study, we
      clarified the essence of micro-topography and laid a theoretical foundation for
      further understanding diverse hydrological processes.

PMID- 29472579
TI  - Single-molecule theory of enzymatic inhibition.
AB  - The classical theory of enzymatic inhibition takes a deterministic, bulk based
      approach to quantitatively describe how inhibitors affect the progression of
      enzymatic reactions. Catalysis at the single-enzyme level is, however, inherently
      stochastic which could lead to strong deviations from classical predictions. To
      explore this, we take the single-enzyme perspective and rebuild the theory of
      enzymatic inhibition from the bottom up. We find that accounting for multi
      conformational enzyme structure and intrinsic randomness should strongly change
      our view on the uncompetitive and mixed modes of inhibition. There, stochastic
      fluctuations at the single-enzyme level could make inhibitors act as activators;
      and we state-in terms of experimentally measurable quantities-a mathematical
      condition for the emergence of this surprising phenomenon. Our findings could
      explain why certain molecules that inhibit enzymatic activity when substrate
      concentrations are high, elicit a non-monotonic dose response when substrate
      concentrations are low.

PMID- 29472581
TI  - Wavelength Assignment in Hybrid Quantum-Classical Networks.
AB  - Optimal wavelength assignment in dense-wavelength-division-multiplexing (DWDM)
      systems that integrate both quantum and classical channels is studied. In such
      systems, weak quantum key distribution (QKD) signals travel alongside intense
      classical signals on the same fiber, where the former can be masked by the
      background noise induced by the latter. Here, we investigate how optimal
      wavelength assignment can mitigate this problem. We consider different DWDM
      structures and various sources of crosstalk and propose several near-optimal
      wavelength assignment methods that maximize the total secret key rate of the QKD
      channels. Our numerical results show that the optimum wavelength assignment
      pattern is commonly consisted of several interspersed quantum and classical
      bands. Using our proposed techniques, the total secret key rate of quantum
      channels can substantially be improved, as compared to conventional assignment
      methods, in the noise dominated regimes. Alternatively, we can maximize the
      number of QKD users supported under certain key rate constraints.

PMID- 29472582
TI  - P2X7 receptor regulates osteoclast function and bone loss in a mouse model of
      osteoporosis.
AB  - Post-menopausal osteoporosis is a condition that affects millions worldwide and
      places a huge socio-economic burden on society. Previous research has shown an
      association of loss of function SNPs in the gene for the purinergic receptor
      P2X7R with low bone mineral density, increased rates of bone loss and vertebral
      fractures in post-menopausal women. In this study we use a mouse model of
      oestrogen deficiency-induced bone loss and the BALB/cJ P2X7R-/- to show that
      absence of the P2X7R resulted in increased bone loss. Osteoclast precursors were
      isolated from both BALB/cJ P2X7R-/- and BALB/cJ P2X7R+/+ mice and then cultured
      in vitro to form mature resorbing osteoclasts. The BALB/cJ P2X7R-/- derived
      precursors generated slightly more osteoclasts but with a significant reduction
      in the amount of resorption per osteoclast. Furthermore, when using modified
      culture conditions osteoclast activity was additionally increased in the absence
      of the P2X7R suggest that P2X7R may regulate the lifespan and activity of
      osteoclasts. Finally using mechanical loading as an anabolic stimulus for bone
      formation, we demonstrated that the increased oestrogen-deficient bone loss could
      be rescued, even in the absence of P2X7R. This study paves the way for clinical
      intervention for women with post-menopausal osteoporosis and P2XR7 loss of
      function polymorphisms.

PMID- 29472583
TI  - Antitumor activities of Quercetin and Green Tea in xenografts of human leukemia
      HL60 cells.
AB  - Quercetin is one of the most abundant flavonoids, present in fruits and
      vegetables and has been shown to have multiple properties capable of reducing
      cell growth in cancer cells. Green tea is a widely consumed beverage, known for a
      potential source of free radical scavenging and anti-cancer activities. Herein,
      we investigate the in vivo antitumor efficacy of quercetin and green tea in human
      leukemia. Human tumors were xenografted into NOD/SCID mice. Quercetin and green
      tea reduced tumor growth in HL-60 xenografts accompanied by decreased expression
      of anti-apoptotic proteins, BCL-2, BCL-XL and MCL-1 and increased expression of
      BAX, a pro-apoptotic protein. Moreover, caspase-3 was activated to a greater
      extent after quercetin and green tea treatment. Quercetin and green tea also
      mediated G1 phase cell cycle arrest in HL-60 xenografts. Treatment with quercetin
      and green tea induced conversion of LC3-I to LC3-II as well as activation of
      autophagy proteins, suggesting that quercetin and green tea initiate the
      autophagic progression. We have provided evidence that quercetin and green tea
      induces signaling at the level of apoptosis, cell cycle and autophagy which
      converge to antigrowth effects in HL-60 xenograft mice suggesting that these
      compounds may be a compelling ally in cancer treatment.

PMID- 29472584
TI  - The structure of iPLA2beta reveals dimeric active sites and suggests mechanisms
      of regulation and localization.
AB  - Calcium-independent phospholipase A2beta (iPLA2beta) regulates important
      physiological processes including inflammation, calcium homeostasis and
      apoptosis. It is genetically linked to neurodegenerative disorders including
      Parkinson's disease. Despite its known enzymatic activity, the mechanisms
      underlying iPLA2beta-induced pathologic phenotypes remain poorly understood.
      Here, we present a crystal structure of iPLA2beta that significantly revises
      existing mechanistic models. The catalytic domains form a tight dimer. They are
      surrounded by ankyrin repeat domains that adopt an outwardly flared orientation,
      poised to interact with membrane proteins. The closely integrated active sites
      are positioned for cooperative activation and internal transacylation. The
      structure and additional solution studies suggest that both catalytic domains can
      be bound and allosterically inhibited by a single calmodulin. These features
      suggest mechanisms of iPLA2beta cellular localization and activity regulation,
      providing a basis for inhibitor development. Furthermore, the structure provides
      a framework to investigate the role of neurodegenerative mutations and the
      function of iPLA2beta in the brain.

PMID- 29472586
TI  - Ocean submesoscales as a key component of the global heat budget.
AB  - Recent studies highlight that oceanic motions associated with horizontal scales
      smaller than 50 km, defined here as submesoscales, lead to anomalous vertical
      heat fluxes from colder to warmer waters. This unique transport property is not
      captured in climate models that have insufficient resolution to simulate these
      submesoscale dynamics. Here, we use an ocean model with an unprecedented
      resolution that, for the first time, globally resolves submesoscale heat
      transport. Upper-ocean submesoscale turbulence produces a systematically-upward
      heat transport that is five times larger than mesoscale heat transport, with
      winter-time averages up to 100 W/m2 for mid-latitudes. Compared to a lower
      resolution model, submesoscale heat transport warms the sea surface up to 0.3 
      degrees C and produces an upward annual-mean air-sea heat flux anomaly of 4-10
      W/m2 at mid-latitudes. These results indicate that submesoscale dynamics are
      critical to the transport of heat between the ocean interior and the atmosphere,
      and are thus a key component of the Earth's climate.

PMID- 29472585
TI  - Estradiol signaling mediates gender difference in visceral adiposity via
      autophagy.
AB  - Excessive adiposity (particularly visceral fat mass) increases the risks of
      developing metabolic syndrome. Women have lower deposit of visceral fat than men,
      and this pattern becomes diminished postmenopausally, but the underlying
      mechanism remains largely unknown. Here, we show that the gender difference in
      visceral fat distribution is controlled by an estradiol-autophagy axis. In
      C57BL/6J and wild-type control mice, a higher visceral fat mass was detected in
      the males than in the females, which was associated with lower expression of
      estrogen receptor alpha (ERalpha) and more active autophagy in males vs. females.
      However, deletion of ERalpha normalized autophagy activity and abolished the
      gender difference in visceral adiposity. In line with the adiposity-reducing
      effect of the ERalpha-autophagy axis, we found that downregulation of ERalpha and
      increased autophagy activity were required for adipogenesis, while induction of
      estradiol signaling dampened autophagy and drastically prevented adipogenesis.
      Mechanistically, the estradiol-ERalpha signaling activated mTOR, which
      phosphorylated and inhibited ULK1, thereby suppressing autophagy and
      adipogenesis. Together, our study suggests that the lower visceral adiposity in
      the females (vs. the males) arises from a more active estradiol-ERalpha
      signaling, which tunes down autophagy and adipogenesis.

PMID- 29472587
TI  - Association of BRCA1, ERCC1, RAP80, PKM2, RRM1, RRM2, TS, TSP1, and TXR1 mRNA
      expression levels between primary tumors and infiltrated regional lymph nodes in
      patients with resectable non-small cell lung cancer.
AB  - Differences in gene expression levels between the primary tumors (PTs) and
      matched regional lymph nodal metastases (LNs) in patients with totally excised
      non-small cell lung cancer (NSCLC) were explored. Microdissected formalin-fixed
      paraffin-embedded (FFPE) samples from (PT) and their matched infiltrated LNs,
      from 239 patients [183 (with matched PT and LNs samples)-case and 56 PT only
      samples-control cohorts] were analyzed for BRCA1, ERCC1, RAP80, PKM2, RRM1, RRM2,
      TS, TSP1, and TXR1 mRNA expression by quantitative real-time polymerase-chain
      reaction (PCR). Moderately positive correlation between the expression of each
      gene in the PT and the matched LNs was observed. Concordance rates between the PT
      and the LNs were: BRCA1 (67.7%), ERCC1 (68.4%), PKM2 (63.4%), RAP80 (68.8%), RRM1
      (70.9%), RRM2 (69%), TS (72.9%), TSP1 (69.8%), TXR1 (63.7%). Expression levels
      and their differences were correlated with Relapse-Free Survival (RFS) and
      Overall Survival (OS). High BRCA1 PT in patients with squamous histology was
      associated with increased OS (p = 0.036). High TSP1 PT levels were shown to be
      the only independent prognostic factor for OS and RFS (p = 0.023 and p = 0.007).
      PKM2 low levels in both PT and matched LNs were associated with better OS
      irrespective of the underlying histology (p = 0.031). RRM1 discordant levels
      between PT and matched LNs were associated with worse OS in squamous tumors (p =
      0.019) compared to patients with both low expression in PT and LN.TXR1 high
      levels in both PT and matched LNs were associated with better OS in patients with
      squamous tumors (p = 0.007).These findings indicate that there is different gene
      expression between PT and matched LNs which may affect the outcome in early NSCLC
      and therefore PT's molecular biology should not be the sole determinant for
      prognostication.

PMID- 29472588
TI  - Micro-pharmacokinetics: Quantifying local drug concentration at live cell
      membranes.
AB  - Fundamental equations for determining pharmacological parameters, such as the
      binding affinity of a ligand for its target receptor, assume a homogeneous
      distribution of ligand, with concentrations in the immediate vicinity of the
      receptor being the same as those in the bulk aqueous phase. It is, however, known
      that drugs are able to interact directly with the plasma membrane, potentially
      increasing local ligand concentrations around the receptor. We have previously
      reported an influence of ligand-phospholipid interactions on ligand binding
      kinetics at the beta2-adrenoceptor, which resulted in distinct "micro
      pharmacokinetic" ligand profiles. Here, we directly quantified the local
      concentration of BODIPY630/650-PEG8-S-propranolol (BY-propranolol), a fluorescent
      derivative of the classical beta-blocker propranolol, at various distances above
      membranes of single living cells using fluorescence correlation spectroscopy. We
      show for the first time a significantly increased ligand concentration
      immediately adjacent to the cell membrane compared to the bulk aqueous phase. We
      further show a clear role of both the cell membrane and the beta2-adrenoceptor in
      determining high local BY-propranolol concentrations at the cell surface. These
      data suggest that the true binding affinity of BY-propranolol for the beta2
      adrenoceptor is likely far lower than previously reported and highlights the
      critical importance of understanding the "micro-pharmacokinetic" profiles of
      ligands for membrane-associated proteins.

PMID- 29472589
TI  - Computationally Efficient Modelling of Stochastic Spatio-Temporal Dynamics in
      Biomolecular Networks.
AB  - Measurement techniques in biology are now able to provide data on the
      trajectories of multiple individual molecules simultaneously, motivating the
      development of techniques for the stochastic spatio-temporal modelling of
      biomolecular networks. However, standard approaches based on solving stochastic
      reaction-diffusion equations are computationally intractable for large-scale
      networks. We present a novel method for modeling stochastic and spatial dynamics
      in biomolecular networks using a simple form of the Langevin equation with noisy
      kinetic constants. Spatial heterogeneity in molecular interactions is decoupled
      into a set of compartments, where the distribution of molecules in each
      compartment is idealised as being uniform. The reactions in the network are then
      modelled by Langevin equations with correcting terms, that account for
      differences between spatially uniform and spatially non-uniform distributions,
      and that can be readily estimated from available experimental data. The accuracy
      and extreme computational efficiency of the approach is demonstrated on a model
      of the epidermal growth factor receptor network in the human mammary epithelial
      cell.

PMID- 29472590
TI  - Elevated Serum Interleukin-34 Level in Patients with Systemic Lupus Erythematosus
      Is Associated with Disease Activity.
AB  - We measured the interleukin-34 (IL-34) level in sera from patients with systemic
      lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) using an enzyme
      linked immunosorbent assay (ELISA). Blood tests, including assays to determine C
      reactive protein (CRP), complement (C) 3, C4, immunoglobulin (Ig) A, IgG, IgM,
      anti-double-stranded DNA antibody (Anti-dsDNA Ab) and hemoglobin (Hb) levels and
      white blood cell (WBC) and platelet (PLT) counts, were performed using standard
      methods. Lupus nephritis (LN) was diagnosed according to the American College of
      Rheumatology (ACR) renal criteria. The SLE disease activity was scored using the
      SLE Disease Activity Index (SLEDAI). Among the 110 SLE cases, IL-34 could be
      detected in 79 cases (71.8%). IL-34 was barely detected in the control group. The
      serum level of IL-34 was significantly higher in the SLE group. No change was
      observed in the serum IL-34 concentration in the SLE patients regardless of LN
      status. Correlations were observed between the serum IL-34 level and the disease
      activity parameters. The SLE patients with detectable IL-34 levels had higher
      SLEDAI and IgG concentrations and lower C3 and Hb levels than patients with
      undetectable IL-34 levels. Therefore, IL-34 could be a potential disease activity
      marker for SLE.

PMID- 29472591
TI  - Early sclerostin expression explains bone formation inhibition before arthritis
      onset in the rat adjuvant-induced arthritis model.
AB  - Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly
      related to synovial inflammation. However, strong bone loss has also described at
      the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage
      was described when blocking sclerostin in various arthritis models. Thus, we
      aimed to determine kinetics of bone loss and its mechanisms in the adjuvant
      induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35)
      at day 0. In addition to well-known arthritis at day 12, we showed with 3D
      imaging and histomorphometry that bone microstructural alterations occurred early
      from day 8 post-induction, characterized by cortical porosity and trabecular bone
      loss. Active osteoclastic surfaces were increased from day 8 with RANKL
      upregulation. More surprisingly SOST and DKK1 were overexpressed from day 6 and
      followed by a dramatic decrease in bone formation from day 8. At the time of
      arthritis onset, SOST and DKK1 returned to control values, but frizzled related
      protein 1 (SFRP1), proinflammatory cytokines, and MMPs started to increase. Bone
      alterations before arthritis onset reinforce the hypothesis of an early bone
      involvement in arthritis. Kinetics of osteocyte markers expression should be
      considered to refine Wnt inhibitor treatment strategies.

PMID- 29472592
TI  - GSK3 is a negative regulator of the thermogenic program in brown adipocytes.
AB  - Brown adipose tissue is a promising therapeutic target in metabolic disorders due
      to its ability to dissipate energy and improve systemic insulin sensitivity and
      glucose homeostasis. beta-Adrenergic stimulation of brown adipocytes leads to an
      increase in oxygen consumption and induction of a thermogenic gene program that
      includes uncoupling protein 1 (Ucp1) and fibroblast growth factor 21 (Fgf21). In
      kinase inhibitor screens, we have identified glycogen synthase kinase 3 (GSK3) as
      a negative regulator of basal and beta-adrenergically stimulated Fgf21 expression
      in cultured brown adipocytes. In addition, inhibition of GSK3 also caused
      increased Ucp1 expression and oxygen consumption. beta-Adrenergic stimulation
      triggered an inhibitory phosphorylation of GSK3 in a protein kinase A (PKA)
      dependent manner. Mechanistically, inhibition of GSK3 activated the mitogen
      activated protein kinase (MAPK) kinase 3/6-p38 MAPK-activating transcription
      factor 2 signaling module. In summary, our data describe GSK3 as a novel negative
      regulator of beta-adrenergic signaling in brown adipocytes.

PMID- 29472593
TI  - The relationship between self-enhancing humor and precuneus volume in young
      healthy individuals with high and low cognitive empathy.
AB  - A self-enhancing humor style (SEHS) plays an important role in the regulation of
      negative emotion through humorous perspective-taking. Following the mind-reading
      theories of humor, we investigated the relationship between gray-matter volume
      (GMV) of brain areas related to theory of mind and SEHS in young college
      students, using voxel-based morphometry analysis. We then performed a voxel-wise
      analysis of covariance to assess any moderation effect of cognitive empathy on
      the relationship. Results demonstrated that higher SEHS scores were associated
      with larger GMV of the precuneus in the group with high cognitive empathy, but
      there was no association in the group with low cognitive empathy. These results
      suggest that high cognitive empathy and increased precuneus volume can predict
      greater use of self-enhancing humor in young healthy individuals.

PMID- 29472594
TI  - Association between autonomic control indexes and mortality in subjects admitted
      to intensive care unit.
AB  - This study checks whether autonomic markers derived from spontaneous fluctuations
      of heart period (HP) and systolic arterial pressure (SAP) and from their
      interactions with spontaneous or mechanical respiration (R) are associated with
      mortality in patients admitted to intensive care unit (ICU). Three-hundred
      consecutive HP, SAP and R values were recorded during the first day in ICU in 123
      patients. Population was divided into survivors (SURVs, n = 83) and non-survivors
      (NonSURVs, n = 40) according to the outcome. SURVs and NonSURVs were aged- and
      gender-matched. All subjects underwent modified head-up tilt (MHUT) by tilting
      the bed back rest segment to 60 degrees . Autonomic control indexes were computed
      using time-domain, spectral, cross-spectral, complexity, symbolic and causality
      techniques via univariate, bivariate and conditional approaches. SAP indexes
      derived from time-domain, model-free complexity and symbolic approaches were
      associated with the endpoint, while none of HP variability markers was. The
      association was more powerful during MHUT. Linear cross-spectral and causality
      indexes were useless to separate SURVs from NonSURVs, while nonlinear bivariate
      symbolic markers were successful. When indexes were combined with clinical
      scores, only SAP variance provided complementary information. Cardiovascular
      control variability indexes, especially when derived after an autonomic challenge
      such as MHUT, can improve mortality risk stratification in ICU.

PMID- 29472595
TI  - A motif within the armadillo repeat of Parkinson's-linked LRRK2 interacts with
      FADD to hijack the extrinsic death pathway.
AB  - In experimental models, both in vivo and cellular, over-expression of Parkinson's
      linked mutant leucine-rich repeat kinase 2 (LRRK2) is sufficient to induce
      neuronal death. While several cell death associated proteins have been linked to
      LRRK2, either as protein interactors or as putative substrates, characterization
      of the neuronal death cascade remains elusive. In this study, we have mapped for
      the first time the domain within LRRK2 that mediates the interaction with FADD,
      thereby activating the molecular machinery of the extrinsic death pathway. Using
      homology modeling and molecular docking approaches, we have identified a critical
      motif within the N-terminal armadillo repeat region of LRRK2. Moreover, we show
      that co-expression of fragments of LRRK2 that contain the FADD binding motif, or
      deletion of this motif itself, blocks the interaction with FADD, and is
      neuroprotective. We further demonstrate that downstream of FADD, the
      mitochondrial proteins Bid and Bax are recruited to the death cascade and are
      necessary for neuronal death. Our work identifies multiple novel points within
      neuronal death signaling pathways that could potentially be targeted by candidate
      therapeutic strategies and highlight how the extrinsic pathway can be activated
      intracellularly in a pathogenic context.

PMID- 29472596
TI  - HDAC4 regulates satellite cell proliferation and differentiation by targeting P21
      and Sharp1 genes.
AB  - Skeletal muscle exhibits a high regenerative capacity, mainly due to the ability
      of satellite cells to replicate and differentiate in response to appropriate
      stimuli. Epigenetic control is effective at different stages of this process. It
      has been shown that the chromatin-remodeling factor HDAC4 is able to regulate
      satellite cell proliferation and commitment. However, its molecular targets are
      still uncovered. To explain the signaling pathways regulated by HDAC4 in
      satellite cells, we generated tamoxifen-inducible mice with conditional
      inactivation of HDAC4 in Pax7+ cells (HDAC4 KO mice). We found that the
      proliferation and differentiation of HDAC4 KO satellite cells were compromised,
      although similar amounts of satellite cells were found in mice. Moreover, we
      found that the inhibition of HDAC4 in satellite cells was sufficient to block the
      differentiation process. By RNA-sequencing analysis we identified P21 and Sharp1
      as HDAC4 target genes. Reducing the expression of these target genes in HDAC4 KO
      satellite cells, we also defined the molecular pathways regulated by HDAC4 in the
      epigenetic control of satellite cell expansion and fusion.

PMID- 29472597
TI  - Role of autophagy in modulating post-maturation aging of mouse oocytes.
AB  - Mechanisms for post-maturation oocyte aging (PMOA) are not fully understood, and
      whether autophagy plays any role in PMOA is unknown. To explore the role of
      autophagy in PMOA, expression of autophagosomes and effects of the autophagy
      (macro-autophagy) activity on PMOA were observed in mouse oocytes. Oocyte
      activation rates and active caspase-3 levels increased continuously from 0 to 18
      h of in vitro aging. While levels of microtubule-associated protein light chain 3
      (LC3)-II increased up to 12 h and decreased thereafter, contents of p62 decreased
      from 0 to 12 h and then elevated to basal level by 18 h. However, the LC3-II/I
      ratio remained unchanged following aging in different media or for different
      times. During in vitro aging up to 12 h, upregulating autophagy with rapamycin or
      lithium chloride decreased activation susceptibility, cytoplasmic calcium, p62
      contents, oxidative stress, caspase-3 activation and cytoplasmic fragmentation
      while increasing developmental competence, LC3-II contents, LC3-II/I ratio,
      mitochondrial membrane potential, spindle/chromosome integrity and normal
      cortical granule distribution. Downregulating autophagy with 3-methyladenine (3
      MA) produced opposite effects on all these parameters except cytoplasmic
      fragmentation. After 12 h of aging culture, however, regulating autophagy with
      either rapamycin/lithium chloride or 3-MA had no impact on oocyte activation
      susceptibility. It is concluded that autophagy plays an important role in
      regulating PMOA. Thus, during the early stage of PMOA, autophagy increases as an
      adaptive response to prevent further apoptosis, but by the late stage of PMOA,
      the activation of more caspases blocks the autophagic process leading to severer
      apoptosis.

PMID- 29472598
TI  - Climate-Driven Crop Yield and Yield Variability and Climate Change Impacts on the
      U.S. Great Plains Agricultural Production.
AB  - Climate variability and trends affect global crop yields and are characterized as
      highly dependent on location, crop type, and irrigation. U.S. Great Plains, due
      to its significance in national food production, evident climate variability, and
      extensive irrigation is an ideal region of investigation for climate impacts on
      food production. This paper evaluates climate impacts on maize, sorghum, and
      soybean yields and effect of irrigation for individual counties in this region by
      employing extensive crop yield and climate datasets from 1968-2013. Variability
      in crop yields was a quarter of the regional average yields, with a quarter of
      this variability explained by climate variability, and temperature and
      precipitation explained these in singularity or combination at different
      locations. Observed temperature trend was beneficial for maize yields, but
      detrimental for sorghum and soybean yields, whereas observed precipitation trend
      was beneficial for all three crops. Irrigated yields demonstrated increased
      robustness and an effective mitigation strategy against climate impacts than
      their non-irrigated counterparts by a considerable fraction. The information,
      data, and maps provided can serve as an assessment guide for planners, managers,
      and policy- and decision makers to prioritize agricultural resilience efforts and
      resource allocation or re-allocation in the regions that exhibit risk from
      climate variability.

PMID- 29472599
TI  - Acute effects of air pollution on respiratory disease mortalities and outpatients
      in Southeastern China.
AB  - The objective of this study was to investigate the potential association between
      air pollutants and respiratory diseases (RDs). Generalized additive models were
      used to analyze the effect of air pollutants on mortalities or outpatient visits.
      The average concentrations of air pollutants in Hangzhou (HZ) were 1.6-2.8 times
      higher than those in Zhoushan (ZS), except for O3. In a single pollutant model,
      the increased concentrations of PM2.5, NO2, and SO2 were strongly associated with
      deaths caused by RD in HZ, while PM2.5 and O3 were associated with deaths caused
      by RD in ZS. All air pollutants (PM2.5, NO2, SO2, and O3) were strongly
      associated with outpatient visits for RD in both HZ and ZS. In multiple pollutant
      models, a significant association was only observed between PM2.5 and the
      mortality rate of RD patients in both HZ and in ZS. Moreover, strong associations
      between SO2, NO2, and outpatient visits for RD were observed in HZ and ZS. This
      study has provided evidence that both the mortality rates and outpatient visits
      for RD were significantly associated with air pollutants. Furthermore, the
      results showed that different air pollutant levels lead to regional differences
      between mortality rates and outpatient visits.

PMID- 29472600
TI  - PANDA: Protein function prediction using domain architecture and affinity
      propagation.
AB  - We developed PANDA (Propagation of Affinity and Domain Architecture) to predict
      protein functions in the format of Gene Ontology (GO) terms. PANDA at first
      executes profile-profile alignment algorithm to search against PfamA, KOG, COG,
      and SwissProt databases, and then launches PSI-BLAST against UniProt for
      homologue search. PANDA integrates a domain architecture inference algorithm
      based on the Bayesian statistics that calculates the probability of having a GO
      term. All the candidate GO terms are pooled and filtered based on Z-score. After
      that, the remaining GO terms are clustered using an affinity propagation
      algorithm based on the GO directed acyclic graph, followed by a second round of
      filtering on the clusters of GO terms. We benchmarked the performance of all the
      baseline predictors PANDA integrates and also for every pooling and filtering
      step of PANDA. It can be found that PANDA achieves better performances in terms
      of area under the curve for precision and recall compared to the baseline
      predictors. PANDA can be accessed from http://dna.cs.miami.edu/PANDA/ .

PMID- 29472601
TI  - Reactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type
      Ca2+ Channels by Angiotensin II.
AB  - Vascular T-type Ca2+ channels (CaV3.1 and CaV3.2) play a key role in arterial
      tone development. This study investigated whether this conductance is a
      regulatory target of angiotensin II (Ang II), a vasoactive peptide that
      circulates and which is locally produced within the arterial wall. Patch clamp
      electrophysiology performed on rat cerebral arterial smooth muscle cells reveals
      that Ang II (100 nM) inhibited T-type currents through AT1 receptor activation.
      Blocking protein kinase C failed to eliminate channel suppression, a finding
      consistent with unique signaling proteins enabling this response. In this regard,
      inhibiting NADPH oxidase (Nox) with apocynin or ML171 (Nox1 selective) abolished
      channel suppression highlighting a role for reactive oxygen species (ROS). In the
      presence of Ni2+ (50 uM), Ang II failed to modulate the residual T-type current,
      an observation consistent with this peptide targeting CaV3.2. Selective channel
      suppression by Ang II impaired the ability of CaV3.2 to alter spontaneous
      transient outward currents or vessel diameter. Proximity ligation assay confirmed
      Nox1 colocalization with CaV3.2. In closing, Ang II targets CaV3.2 channels via a
      signaling pathway involving Nox1 and the generation of ROS. This unique
      regulatory mechanism alters BKCa mediated feedback giving rise to a
      "constrictive" phenotype often observed with cerebrovascular disease.

PMID- 29472602
TI  - HPV-transformed cells exhibit altered HMGB1-TLR4/MyD88-SARM1 signaling axis.
AB  - Cervical cancer is one of the leading causes of cancer death in women worldwide.
      Persistent infection with high-risk human papillomavirus (HPV) types is the main
      risk factor for the development of cervical cancer precursor lesions. HPV
      persistence and tumor development is usually characterized by innate immune
      system evasion. Alterations in Toll-like receptors (TLR) expression and
      activation may be important for the control of HPV infections and could play a
      role in the progression of lesions and tumors. In the present study, we analyzed
      the mRNA expression of 84 genes involved in TLR signaling pathways. We observed
      that 80% of the differentially expressed genes were downregulated in cervical
      cancer cell lines relative to normal keratinocytes. Major alterations were
      detected in genes coding for several proteins of the TLR signaling axis,
      including TLR adaptor molecules and genes associated with MAPK pathway, NFkappaB
      activation and antiviral immune response. In particular, we observed major
      alterations in the HMGB1-TLR4 signaling axis. Functional analysis also showed
      that HMGB1 expression is important for the proliferative and tumorigenic
      potential of cervical cancer cell lines. Taken together, these data indicate that
      alterations in TLR signaling pathways may play a role in the oncogenic potential
      of cells expressing HPV oncogenes.

PMID- 29472603
TI  - Bronchial extracellular matrix from COPD patients induces altered gene expression
      in repopulated primary human bronchial epithelial cells.
AB  - Chronic obstructive pulmonary disease (COPD) is a serious global health problem
      characterized by chronic airway inflammation, progressive airflow limitation and
      destruction of lung parenchyma. Remodeling of the bronchial airways in COPD
      includes changes in both the bronchial epithelium and the subepithelial
      extracellular matrix (ECM). To explore the impact of an aberrant ECM on
      epithelial cell phenotype in COPD we developed a new ex vivo model, in which
      normal human bronchial epithelial (NHBE) cells repopulate and differentiate on
      decellularized human bronchial scaffolds derived from COPD patients and healthy
      individuals. By using transcriptomics, we show that bronchial ECM from COPD
      patients induces differential gene expression in primary NHBE cells when compared
      to normal bronchial ECM. The gene expression profile indicated altered activity
      of upstream mediators associated with COPD pathophysiology, including hepatocyte
      growth factor, transforming growth factor beta 1 and platelet-derived growth
      factor B, which suggests that COPD-related changes in the bronchial ECM
      contribute to the defective regenerative ability in the airways of COPD patients.

PMID- 29472604
TI  - A non-invasive method to directly quantify surface heterogeneity of porous
      materials.
AB  - It is extremely challenging to measure the variation of pore surface properties
      in complex porous systems even though many porous materials have widely differing
      pore surface properties at microscopic levels. The surface heterogeneity results
      in different adsorption/desorption behaviors and storage capacity of guest
      molecules in pores. Built upon the conventional Porod's law scattering theory
      applicable mainly to porous materials with relatively homogeneous matrices, here
      we develop a generalized Porod's scattering law method (GPSLM) to study
      heterogeneous porous materials and directly obtain the variation of scattering
      length density (SLD) of pore surfaces. As SLD is a function of the chemical
      formula and density of the matrix, the non-invasive GPSLM provides a way to probe
      surface compositional heterogeneity, and can be applied to a wide range of
      heterogeneous materials especially, but not limited to, porous media and
      colloids, using either neutron or X-ray scattering techniques.

PMID- 29472605
TI  - DEHP deregulates adipokine levels and impairs fatty acid storage in human SGBS
      adipocytes.
AB  - DEHP is a plasticizer which has been used in plastic products of everyday use for
      decades. Studies in mice and murine cell culture models identified DEHP as an
      endocrine disruptor that may also act as an obesogen. As this is of high concern
      in respect of the worldwide obesity epidemic, our aim is the translation of these
      findings into a human model system. On the basis of DOHaD, we investigated the
      influence of an environmentally relevant dose of DEHP [50 ug/ml] on adipogenesis
      in the human cell culture model SGBS. Pre-adipocytes were exposed to DEHP and
      differentiated into mature adipocytes. At different stages of differentiation,
      markers of adipogenesis like GLUT4, FABP4, LPL and PPARs, and of signaling
      pathways like AMPK/ACC2, JAK/STAT and MAPK were analyzed. Functional markers like
      adipokine secretion and triglyceride content as well as ROS production were
      measured in mature adipocytes. We found significantly lower expression levels of
      adipogenic markers, a reduction in lipid accumulation, higher leptin- and reduced
      adiponectin levels in the supernatant of treated adipocytes. Moreover, ROS
      production was significantly elevated after DEHP-exposure. In conclusion, DEHP
      led to lower grade of adipogenic differentiation in human SGBS-adipocytes under
      the chosen conditions.

PMID- 29472606
TI  - Nanogels of dual inhibitor-modified hyaluronic acid function as a potent
      inhibitor of amyloid beta-protein aggregation and cytotoxicity.
AB  - Inhibition of amyloid beta-protein (Abeta) aggregation is considered as a
      promising strategy for the prevention and treatment of Alzheimer's disease.
      Epigallocatechin-3-gallate (EGCG) and curcumin have been recognized as effective
      inhibitors of Abeta aggregation. Herein, we proposed dual-inhibitor modification
      of hyaluronic acid (HA) to explore the synergistic effect of the two inhibitors.
      EGCG-modified HA (EHA) formed dispersed hydrogel structures, while EGCG-curcumin
      bi-modified HA (CEHA) self-assembled into nanogels like curcumin-modified HA
      (CHA). Thioflavin T fluorescent assays revealed that the inhibitory effect of
      CEHA was 69% and 55% higher than EHA and CHA, respectively, and cytotoxicity
      assays showed that the viability of SH-SY5Y cells incubated with Abeta and CEHA
      was 28% higher than that with Abeta and the mixture of EHA and CHA. These results
      clearly indicate the synergism of the two inhibitors. It is considered that the
      difference in the hydrophobicities of the two inhibitors made the bi-modification
      of HA provide a favorable CEHA nanostructure that coordinated different
      inhibition effects of the two inhibitors. This research indicates that
      fabrication of dual-inhibitor nanosystem is promising for the development of
      potent agents against Abeta aggregation and cytotoxicity.

PMID- 29472607
TI  - Cell transplantation and clinical reality: Kuwait experience in persons with
      spinal cord injury.
AB  - STUDY DESIGN: Retrospective observational. OBJECTIVES: To compare objective
      (neurological examination) and subjective (patients perception) recovery in
      patients with spinal cord injury (SCI) who chose to undergo cell transplantation
      therapies (CTT) outside of clinical trials abroad. SETTING: Physical Medicine and
      Rehabilitation Hospital, Kuwait. METHODS: Nine patients with SCI who had
      undergone CTT outside Kuwait were identified and their neurological pre
      transplantation evaluation according the International Standards for Neurological
      Classification of SCI (ISNCSCI) was collected from hospital records. Post
      transplantation ISNCSCI examination was conducted during follow-up visits and
      scores were completed between pre and post CTT. In addition to the ISNCSCI
      evaluation, change in disability status, and patient's perception of improvement
      after stem cell transplantation were examined. RESULTS: Overall, 8 males and 1
      female with chronic SCI underwent CTT (42 +/- 38.2 months post SCI) in various
      centers (China, Egypt, Germany, India, and Iran). On follow-up post CTT
      assessment (89.2 +/- 36 months post SCI), 55.5% of individuals reported perceived
      improvement as follows: increased deep tissue sensation below the injury (100%)
      or increase in bladder sensation (11.1%). Objective examination after CTT
      revealed that none of the examined individuals demonstrated improvement in their
      motor scores or neurological level of SCI. CONCLUSION: We were not able to
      objectively document clinically useful improvements in sensorimotor, autonomic,
      or functional status in individuals after CTT.

PMID- 29472608
TI  - Cognitive performance of people with traumatic spinal cord injury: a cross
      sectional study comparing people with subacute and chronic injuries.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To assess the impact of spinal
      cord injury (SCI) on cognitive function in individuals with subacute and chronic
      SCI. SETTING: National Hospital for SCI patients (Spain). METHODS: The present
      investigation was designed to determine the nature, pattern, and extent of
      cognitive deficits in a group of participants with subacute (n = 32) and chronic
      (n = 34) SCI, using a comprehensive battery of reliable and validated
      neuropsychological assessments to study a broad range of cognitive functions.
      Twenty-seven able-bodied subjects matched to the groups with SCI for age and
      educational level formed the control group. RESULTS: The neuropsychological
      assessment showed alterations in the domain of attention, processing speed,
      memory and learning, executive functions, and in recognition in participants with
      SCI. The prevalence of cognitive dysfunction in the chronic stage was also
      confirmed at the individual level. The comparison of the neuropsychological
      assessment between the groups with subacute and chronic SCI showed a worsening of
      cognitive functions in those with chronic SCI compared to the group with subacute
      SCI. CONCLUSIONS: In participants with SCI, cognitive dysfunctions are present in
      the subacute stage and worsen over time. From a clinical point of view, we
      confirmed the presence of cognitive dysfunction that may interfere with the first
      stage of rehabilitation which is the most intense and important. Moreover,
      cognitive dysfunction may be important beyond the end of the first stage of
      rehabilitation as it can affect an individual's quality of life and possible
      integration to society.

PMID- 29472609
TI  - Temperature dependence of long coherence times of oxide charge qubits.
AB  - The ability to maintain coherence and control in a qubit is a major requirement
      for quantum computation. We show theoretically that long coherence times can be
      achieved at easily accessible temperatures (such as boiling point of liquid
      helium) in small (i.e., ~10 nanometers) charge qubits of oxide double quantum
      dots when only optical phonons are the source of decoherence. In the regime of
      strong electron-phonon coupling and in the non-adiabatic region, we employ a
      duality transformation to make the problem tractable and analyze the dynamics
      through a non-Markovian quantum master equation. We find that the system
      decoheres after a long time, despite the fact that no energy is exchanged with
      the bath. Detuning the dots to a fraction of the optical phonon energy,
      increasing the electron-phonon coupling, reducing the adiabaticity, or decreasing
      the temperature enhances the coherence time.

PMID- 29472610
TI  - scNMT-seq enables joint profiling of chromatin accessibility DNA methylation and
      transcription in single cells.
AB  - Parallel single-cell sequencing protocols represent powerful methods for
      investigating regulatory relationships, including epigenome-transcriptome
      interactions. Here, we report a single-cell method for parallel chromatin
      accessibility, DNA methylation and transcriptome profiling. scNMT-seq (single
      cell nucleosome, methylation and transcription sequencing) uses a GpC
      methyltransferase to label open chromatin followed by bisulfite and RNA
      sequencing. We validate scNMT-seq by applying it to differentiating mouse
      embryonic stem cells, finding links between all three molecular layers and
      revealing dynamic coupling between epigenomic layers during differentiation.

PMID- 29472611
TI  - Synthesis of armchair graphene nanoribbons from the 10,10'-dibromo-9,9'
      bianthracene molecules on Ag(111): the role of organometallic intermediates.
AB  - We investigate the bottom-up growth of N = 7 armchair graphene nanoribbons (7
      AGNRs) from the 10,10'-dibromo-9,9'-bianthracene (DBBA) molecules on Ag(111) with
      the focus on the role of the organometallic (OM) intermediates. It is
      demonstrated that DBBA molecules on Ag(111) are partially debrominated at room
      temperature and lose all bromine atoms at elevated temperatures. Similar to DBBA
      on Cu(111), debrominated molecules form OM chains on Ag(111). Nevertheless, in
      contrast with the Cu(111) substrate, formation of polyanthracene chains from OM
      intermediates via an Ullmann-type reaction is feasible on Ag(111). Cleavage of C
      Ag bonds occurs before the thermal threshold for the surface-catalyzed activation
      of C-H bonds on Ag(111) is reached, while on Cu(111) activation of C-H bonds
      occurs in parallel with the cleavage of the stronger C-Cu bonds. Consequently,
      while OM intermediates obstruct the Ullmann reaction between DBBA molecules on
      the Cu(111) substrate, they are required for the formation of polyanthracene
      chains on Ag(111). If the Ullmann-type reaction on Ag(111) is inhibited, heating
      of the OM chains produces nanographenes instead. Heating of the polyanthracene
      chains produces 7-AGNRs, while heating of nanographenes causes the formation of
      the disordered structures with the possible admixture of short GNRs.

PMID- 29472613
TI  - Genetic contribution to 'theory of mind' in adolescence.
AB  - Difficulties in 'theory of mind' (the ability to attribute mental states to
      oneself or others, and to make predictions about another's behaviour based on
      these attributions) have been observed in several psychiatric conditions. We
      investigate the genetic architecture of theory of mind in 4,577 13-year-olds who
      completed the Emotional Triangles Task (Triangles Task), a first-order test of
      theory of mind. We observe a small but significant female-advantage on the
      Triangles Task (Cohen's d = 0.19, P < 0.01), in keeping with previous work using
      other tests of theory of mind. Genome-wide association analyses did not identify
      any significant loci, and SNP heritability was non-significant. Polygenic scores
      for six psychiatric conditions (ADHD, anorexia, autism, bipolar disorder,
      depression, and schizophrenia), and empathy were not associated with scores on
      the Triangles Task. However, polygenic scores of cognitive aptitude, and
      cognitive empathy, a term synonymous with theory of mind and measured using the
      "Reading the Mind in the Eyes" Test, were significantly associated with scores on
      the Triangles Task at multiple P-value thresholds, suggesting shared genetics
      between different measures of theory of mind and cognition.

PMID- 29472612
TI  - Sumoylation regulates FMRP-mediated dendritic spine elimination and maturation.
AB  - Fragile X syndrome (FXS) is the most frequent inherited cause of intellectual
      disability and the best-studied monogenic cause of autism. FXS results from the
      functional absence of the fragile X mental retardation protein (FMRP) leading to
      abnormal pruning and consequently to synaptic communication defects. Here we show
      that FMRP is a substrate of the small ubiquitin-like modifier (SUMO) pathway in
      the brain and identify its active SUMO sites. We unravel the functional
      consequences of FMRP sumoylation in neurons by combining molecular replacement
      strategy, biochemical reconstitution assays with advanced live-cell imaging. We
      first demonstrate that FMRP sumoylation is promoted by activation of metabotropic
      glutamate receptors. We then show that this increase in sumoylation controls the
      homomerization of FMRP within dendritic mRNA granules which, in turn, regulates
      spine elimination and maturation. Altogether, our findings reveal the sumoylation
      of FMRP as a critical activity-dependent regulatory mechanism of FMRP-mediated
      neuronal function.

PMID- 29472614
TI  - Painting with light-powered bacteria.
AB  - Self-assembly is a promising route for micro- and nano-fabrication with potential
      to revolutionise many areas of technology, including personalised medicine. Here
      we demonstrate that external control of the swimming speed of microswimmers can
      be used to self assemble reconfigurable designer structures in situ. We implement
      such 'smart templated active self assembly' in a fluid environment by using
      spatially patterned light fields to control photon-powered strains of motile
      Escherichia coli bacteria. The physics and biology governing the sharpness and
      formation speed of patterns is investigated using a bespoke strain designed to
      respond quickly to changes in light intensity. Our protocol provides a distinct
      paradigm for self-assembly of structures on the 10 MUm to mm scale.

PMID- 29472615
TI  - The Effects of Housing Density on Social Interactions and Their Correlations with
      Serotonin in Rodents and Primates.
AB  - Population density has been suggested to affect social interactions of
      individuals, but the underlying neural mechanisms remain unclear. In contrast,
      neurotransmission of monoamines such as serotonin (5-HT) and dopamine (DA) has
      been demonstrated to play important roles in social behaviors. Here, we
      investigated whether housing density affected social interactions of rodents and
      non-human primates housed in groups, and its correlations with monoamines.
      Japanese macaques exhibited higher plasma 5-HT, but not DA, concentrations than
      rhesus macaques. Similarly, C57BL/6 mice exhibited higher plasma and brain tissue
      5-HT concentrations than DBA2 mice. Under crowding, C57BL/6 mice and Japanese
      macaques exhibited more prominent social avoidance with mates than DBA2 mice and
      rhesus macaques, respectively. Although DBA2 mice and rhesus macaques in crowding
      exhibited elevated plasma stress hormones, such stress hormone elevations
      associated with crowding were absent in C57BL/6 mice and Japanese macaques.
      Administration of parachlorophenylalanine, which inhibits 5-HT synthesis,
      increased social interactions and stress hormones in C57BL/6 mice under crowding.
      These results suggest that, animals with hyperserotonemia may exhibit social
      avoidance as an adaptive behavioral strategy to mitigate stress associated with
      crowding environments, which may also be relevant to psychiatric disorder such as
      autism spectrum disorder.

PMID- 29472616
TI  - Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via
      exosomal miR-1246.
AB  - TP53 mutants (mutp53) are involved in the pathogenesis of most human cancers.
      Specific mutp53 proteins gain oncogenic functions (GOFs) distinct from the tumor
      suppressor activity of the wild-type protein. Tumor-associated macrophages
      (TAMs), a hallmark of solid tumors, are typically correlated with poor prognosis.
      Here, we report a non-cell-autonomous mechanism, whereby human mutp53 cancer
      cells reprogram macrophages to a tumor supportive and anti-inflammatory state.
      The colon cancer cells harboring GOF mutp53 selectively shed miR-1246-enriched
      exosomes. Uptake of these exosomes by neighboring macrophages triggers their miR
      1246-dependent reprogramming into a cancer-promoting state. Mutp53-reprogammed
      TAMs favor anti-inflammatory immunosuppression with increased activity of TGF
      beta. These findings, associated with poor survival in colon cancer patients,
      strongly support a microenvironmental GOF role for mutp53 in actively engaging
      the immune system to promote cancer progression and metastasis.

PMID- 29472618
TI  - HIF-1alpha hampers dendritic cell function and Th1 generation during chronic
      visceral leishmaniasis.
AB  - Inflammation, although responsible for controlling infection, is often associated
      with the pathogenesis of chronic diseases. Leishmania donovani, the causative
      agent of visceral leishmaniasis, induces a strong inflammatory response that
      leads to splenomegaly and ultimately immune suppression. Inflamed tissues are
      typically characterized by low levels of oxygen, a microenvironment that triggers
      the hypoxia-inducible transcription factor 1alpha (HIF-1alpha). Although HIF
      1alpha plays an integral role in dendritic cell function, its involvement in the
      generation of protective Th1 responses against Leishmania has not yet been
      studied. Here we demonstrate that HIF-1alpha inhibits IL-12 production in
      dendritic cells, limiting therefore Th1 cell development. Indeed, depletion of
      HIF-1alpha in CD11c+ cells resulted in higher and sustained expression of IL-12
      and complete abrogation of IL-10. Moreover, CD11c-specific HIF-1alpha-deficient
      mice showed higher frequencies of IFN-gamma-producing CD4 T cells in the spleen
      and bone marrow and, consequently, a significantly reduced parasite burden in
      both organs. Taken together, our results suggest that HIF-1alpha expression in
      dendritic cells largely contributes to the establishment of persistent Leishmania
      infection and may therefore represent a possible therapeutic target.

PMID- 29472617
TI  - Whole genome diversity of inherited chromosomally integrated HHV-6 derived from
      healthy individuals of diverse geographic origin.
AB  - Human herpesviruses 6-A and -B (HHV-6A, HHV-6B) are ubiquitous in human
      populations worldwide. These viruses have been associated with several diseases
      such as multiple sclerosis, Hodgkin's lymphoma or encephalitis. Despite of the
      need to understand the genetic diversity and geographic stratification of these
      viruses, the availability of complete viral sequences from different populations
      is still limited. Here, we present nine new inherited chromosomally integrated
      HHV-6 sequences from diverse geographical origin which were generated through
      target DNA enrichment on lymphoblastoid cell lines derived from healthy
      individuals. Integration with available HHV-6 sequences allowed the assessment of
      HHV-6A and -6B phylogeny, patterns of recombination and signatures of natural
      selection. Analysis of the intra-species variability showed differences between A
      and B diversity levels and revealed that the HHV-6B reference (Z29) is an
      uncommon sequence, suggesting the need for an alternative reference sequence.
      Signs of geographical variation are present and more defined in HHV-6A, while
      they appear partly masked by recombination in HHV-6B. Finally, we conducted a
      scan for signatures of selection in protein coding genes that yielded at least 6
      genes (4 and 2 respectively for the A and B species) showing significant evidence
      for accelerated evolution, and 1 gene showing evidence of positive selection in
      HHV-6A.

PMID- 29472619
TI  - Modulating bacterial and gut mucosal interactions with engineered biofilm matrix
      proteins.
AB  - Extracellular appendages play a significant role in mediating communication
      between bacteria and their host. Curli fibers are a class of bacterial fimbria
      that is highly amenable to engineering. We demonstrate the use of engineered
      curli fibers to rationally program interactions between bacteria and components
      of the mucosal epithelium. Commensal E. coli strains were engineered to produce
      recombinant curli fibers fused to the trefoil family of human cytokines. Biofilms
      formed from these strains bound more mucins than those producing wild-type curli
      fibers, and modulated mucin rheology as well. When treated with bacteria
      producing the curli-trefoil fusions mammalian cells behaved identically in terms
      of their migration behavior as when they were treated with the corresponding
      soluble trefoil factors. Overall, this demonstrates the potential utility of
      curli fibers as a scaffold for the display of bioactive domains and an untapped
      approach to rationally modulating host-microbe interactions using bacterial
      matrix proteins.

PMID- 29472620
TI  - Repopulated microglia are solely derived from the proliferation of residual
      microglia after acute depletion.
AB  - Newborn microglia rapidly replenish the whole brain after selective elimination
      of most microglia (>99%) in adult mice. Previous studies reported that
      repopulated microglia were largely derived from microglial progenitor cells
      expressing nestin in the brain. However, the origin of these repopulated
      microglia has been hotly debated. In this study, we investigated the origin of
      repopulated microglia by a series of fate-mapping approaches. We first excluded
      the blood origin of repopulated microglia via parabiosis. With different
      transgenic mouse lines, we then demonstrated that all repopulated microglia were
      derived from the proliferation of the few surviving microglia (<1%). Despite a
      transient pattern of nestin expression in newly forming microglia, none of
      repopulated microglia were derived from nestin-positive non-microglial cells. In
      summary, we conclude that repopulated microglia are solely derived from residual
      microglia rather than de novo progenitors, suggesting the absence of microglial
      progenitor cells in the adult brain.

PMID- 29472621
TI  - Temporal trends of phthalate exposures during 2007-2010 in Swedish pregnant
      women.
AB  - BACKGROUND: The general population is exposed to phthalates, a group of chemicals
      with strong evidence for endocrine disrupting properties, commonly used in a
      large number of consumer products. Based on published research and evidence
      compiled by environmental agencies, certain phthalate applications and products
      have become restricted, leading to an increasing number of "new generation
      compounds" coming onto the market during recent years replacing older phthalates.
      Some examples of such newer compounds are di-iso-nonyl phthalate (DiNP), di-iso
      decyl phthalate (DiDP), and most recently di-isononyl-cyclohexane-1,2
      dicarboxylate (DiNCH). OBJECTIVES: In order to evaluate temporal trends in
      phthalate exposure, first trimester urinary biomarkers of phthalates were
      measured in the Swedish SELMA study over a period of 2.5 years (2007-2010).
      METHODS: We collected first morning void urine samples around week 10 of
      pregnancy from 1651 pregnant women. Spot samples were analyzed for 13 phthalate
      metabolites and one phthalate replacement and least square geometric mean (LSGM)
      levels of the metabolites were compared between the sampling years when adjusted
      for potential confounders. RESULTS: All 14 metabolites were detectable in more
      than 99% of the SELMA subjects. The levels were generally comparable to other
      studies, but the SELMA subjects showed slightly higher exposure to butyl-benzyl
      phthalate (BBzP) and di-butyl phthalate (DBP). Di-ethyl-hexyl phthalate (DEHP)
      metabolites levels decreased while DiNP, DiDP/di-2-propylheptyl phthalate (DPHP),
      and DiNCH metabolites levels increased during the sampling period. CONCLUSIONS:
      Urinary metabolite levels of the older phthalates and more recently introduced
      phthalate replacement compound changed during the short sampling period in this
      Swedish pregnancy cohort. Our results indicate that replacement of phthalates can
      make an impact on human exposure to these chemicals. During this particularly
      vulnerable stage of life, phthalate exposures are of particular concern as the
      impacts, though not immediately noticeable, may increase the risk for health
      effects later in life.

PMID- 29472622
TI  - Aberrant methylated key genes of methyl group metabolism within the molecular
      etiology of urothelial carcinogenesis.
AB  - Urothelial carcinoma (UC), the most common cancer of the urinary bladder causes
      severe morbidity and mortality, e.g. about 40.000 deaths in the EU annually, and
      incurs considerable costs for the health system due to the need for prolonged
      treatments and long-term monitoring. Extensive aberrant  DNA methylation is
      described to prevail in urothelial carcinoma and is thought to contribute to
      genetic instability, altered gene expression and tumor progression. However, it
      is unknown how this epigenetic alteration arises during carcinogenesis. Intact
      methyl group metabolism is required to ensure maintenance of cell-type specific
      methylomes and thereby genetic integrity and proper cellular function. Here,
      using two independent techniques for detecting DNA methylation, we observed DNA
      hypermethylation of the 5'-regulatory regions of the key methyl group metabolism
      genes ODC1, AHCY and MTHFR in early urothelial carcinoma. These hypermethylation
      events are associated with genome-wide DNA hypomethylation which is commonly
      associated with genetic instability. We therefore infer that hypermethylation of
      methyl group metabolism genes acts in a feed-forward cycle to promote additional
      DNA methylation changes and suggest a new hypothesis on the molecular etiology of
      urothelial carcinoma.

PMID- 29472623
TI  - Effectiveness and Safety of Different Rivaroxaban Dosage Regimens in Patients
      with Non-Valvular Atrial Fibrillation: A Nationwide, Population-Based Cohort
      Study.
AB  - The objective of this study is to evaluate the effectiveness of different
      rivaroxaban dosage regimens in preventing ischemic stroke and systemic
      thromboembolism among Asians. A retrospective cohort study was conducted on data
      from nationwide insurance claims in Taiwan. Patients with non-valvular atrial
      fibrillation under warfarin or rivaroxaban therapy were included. Propensity
      score matching was used to balance the covariates, and Cox-proportional hazard
      models were applied to compare the effectiveness and safety of each treatment
      group. Rivaroxaban was associated with a significantly lower risk of venous
      thromboembolism (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.29
      0.92, P = 0.02) and intracranial hemorrhage (HR: 0.48; 95% CI: 0.32-0.72, P <
      0.001) than warfarin. Rivaroxaban 20 mg and 15 mg were associated with a
      significantly lower risk of ischemic stroke (20 mg, HR: 0.48; CI: 0.29-0.80, P =
      0.005; 15 mg, HR: 0.69; CI: 0.53-0.90, P = 0.005), but rivaroxaban 10 mg was not.
      In the subgroup analysis of patients older than 65 years, the results were
      generally the same, except that rivaroxaban had a significantly lower risk of
      ischemic stroke than warfarin.

PMID- 29472624
TI  - Citalopram inhibits platelet function independently of SERT-mediated 5-HT
      transport.
AB  - Citalopram prevents serotonin (5-HT) uptake into platelets by blocking the
      serotonin reuptake transporter (SERT). Although some clinical data suggest that
      selective serotonin reuptake inhibitors (SSRIs) may affect haemostasis and
      thrombosis, these poorly-characterised effects are not well understood
      mechanistically and useful in vitro data is limited. We sought to determine
      whether the inhibitory effects of citalopram on platelets are mediated via its
      pharmacological inhibition of 5-HT transport. We quantified the inhibitory
      potency of (RS)-, (R)- and (S)-citalopram on platelet function. If SERT blockade
      is the primary mechanism for citalopram-mediated platelet inhibition, these
      potencies should show quantitative congruence with inhibition of 5-HT uptake. Our
      data show that citalopram inhibits platelet aggregation, adhesion and thromboxane
      production with no difference in potency between (R)- and (S)-isomers. By
      contrast, citalopram had a eudysmic ratio of approximately 17 (S > R) for SERT
      blockade. Furthermore, nanomolar concentrations of citalopram inhibited 5-HT
      uptake into platelets but had no effect on other platelet functions, which were
      inhibited by micromolar concentrations. Our data indicate that citalopram-induced
      inhibition of platelets in vitro is not mediated by blockade of 5-HT transport.
      This raises a new question for future investigation: by what mechanism(s) does
      citalopram inhibit platelets?

PMID- 29472626
TI  - Nonlinear internal wave spirals in the northern East China Sea.
AB  - Oceanic internal waves are known to be important to the understanding of
      underwater acoustics, marine biogeochemistry, submarine navigation and
      engineering, and the Earth's climate. In spite of the importance and increased
      knowledge of their ubiquity, the wave generation is still poorly understood in
      most parts of the world's oceans. Here, we use satellite synthetic aperture radar
      images, in-situ observations, and numerical models to (1) show that wave energy
      (having relatively high amplitude) radiates from a shallow sill in the East China
      Sea in all directions, but with a significant time lag dependent on background
      conditions, (2) reveal that wave fronts are locally formed with often favorable
      conditions for re-initiation, and (3) demonstrate the resulting variety of wave
      patterns. These findings would be the case for any broad shelf having shallow
      sills with time-varying conditions, and therefore have significant implications
      on the redistribution of energy and materials in the global as well as regional
      ocean.

PMID- 29472625
TI  - The role of medial prefrontal cortex in the working memory maintenance of one's
      own emotional responses.
AB  - The role of medial prefrontal cortex (MPFC) in maintaining emotional information
      within working memory (WM) remains insufficiently investigated - with some
      studies suggesting this process activates MPFC and others suggesting its activity
      is suppressed. To reconcile these different results, we asked 26 healthy
      participants to complete a WM task involving the maintenance of emotional content
      (EWM), visual content (VWM), or no content ("rest") after exposure to emotion
      provoking images. We also assessed individual differences in emotional awareness
      (EA). We observed that dorsal MPFC was more active during EWM than VWM; further,
      relative to the rest condition, both of these WM conditions involved suppression
      of ventral MPFC. We also observed that the dorsal anterior cingulate subregion of
      dorsal MPFC was positively associated with EA. We discuss how these results may
      be able to reconcile the findings of previous EWM studies, and extend
      understanding of the relationship between MPFC, EA, and WM.

PMID- 29472627
TI  - Quantum phase transitions in highly crystalline two-dimensional superconductors.
AB  - Superconductor-insulator transition is one of the remarkable phenomena driven by
      quantum fluctuation in two-dimensional (2D) systems. Such a quantum phase
      transition (QPT) was investigated predominantly on highly disordered thin films
      with amorphous or granular structures using scaling law with constant exponents.
      Here, we provide a totally different view of QPT in highly crystalline 2D
      superconductors. According to the magneto-transport measurements in 2D
      superconducting ZrNCl and MoS2, we found that the quantum metallic state commonly
      observed at low magnetic fields is converted via the quantum Griffiths state to
      the weakly localized metal at high magnetic fields. The scaling behavior,
      characterized by the diverging dynamical critical exponent (Griffiths
      singularity), indicates that the quantum fluctuation manifests itself as
      superconducting puddles, in marked contrast to the thermal fluctuation. We
      suggest that an evolution from the quantum metallic to the quantum Griffiths
      state is generic nature in highly crystalline 2D superconductors with weak
      pinning potentials.

PMID- 29472628
TI  - Ultrastructural and Immunohistochemical Features of Telocytes in Placental Villi
      in Preeclampsia.
AB  - A new cell type, interstitial Cajal-like cell (ICLC), was recently described in
      different organs. The name was recently changed to telocytes (TCs), and their
      typical thin, long processes have been named telopodes (Tp). TCs regulate the
      contractile activity of smooth muscle cells and play a role in regulating vessel
      contractions. Although the placenta is not an innervated organ, we believe that
      TCs are present in the placenta. We studied placenta samples from physiological
      pregnancies and in different variants of preeclampsia (PE). We examined these
      samples using light microscopy of semi-thin sections, transmission electron
      microscopy, and immunohistochemistry. Immunohistochemical examination was
      performed with primary antibodies to CD34, CD117, SMA, and vimentin, and TMEM16a
      (DOG-1), the latter was used for the diagnosis of gastrointestinal stromal
      tumours (GIST) consisting of TCs. We have identified a heterogenetic population
      of TSs in term placentas, as these cell types differed in their localization,
      immunophenotype and ultrastructural characteristics. We assume TMEM16a could be
      used as the marker for identification of TCs. In PE we have revealed telocyte
      like cells with ultrastructural signs of fibrocytes (significant process
      thickening and the granular endoplasmic reticulum content was increased) and a
      loss of TMEM16a immunohistochemical staining.

PMID- 29472629
TI  - Indication to pelvic lymph nodes dissection for prostate cancer: the role of
      multiparametric magnetic resonance imaging when the risk of lymph nodes invasion
      according to Briganti updated nomogram is <5.
AB  - BACKGROUND: The Briganti updated nomogram (BN) is the most popular predictive
      model aiming to predict the presence of lymph node invasion (LNI) in patients
      with prostate cancer (PCa), but it lacks information obtained by preoperative
      imaging. The primary aim of the study was to evaluate the role of multiparametric
      prostate magnetic resonance imaging (mp-MRI) in the indication to perform pelvic
      lymph nodes dissection (PLND) or not in patients with risk of LNI according to BN
      below 5%. METHODS: Since March 2012 and September 2016, 310 patients who
      underwent a preoperative mp-MRI for staging purpose and subsequent robot-assisted
      extended PLND (RAEPLND) were retrospectively evaluated. Mp-MRIs were
      prospectively analyzed by two experienced radiologists. The imaging parameters
      analyzed were the presence of extracapsular extension (ECE), seminal vesicles
      invasion (SVI) and predominant Gleason pattern 4 (pG4). All patients underwent
      RAEPLND by two experienced surgeons with a standardized technique. A dedicated
      uropathologist performed all pathological analysis. Univariate analysis and
      multivariate logistic regression analysis were used in order to identify the
      predictors of LNI in patients with PCa. RESULTS: In the overall population, 57
      (18.4%) patients had histologically proven pN1 disease. 48/250 patients (19.2%)
      with a risk of LNI >=5% as calculated by the BN were staged pN1 at final
      histopathological analysis. 9/60 patients (15.0%) with a risk of LNI <5% as
      calculated by BN, who underwent RAEPLND anyway according to the findings at mp
      MRI, were staged pN1 at final histopathological analysis. At multivariate
      logistic regression analysis, all the three mp-MRI parameters were significant
      independent predictors of LNI after RAEPLND. CONCLUSIONS: The role of mp-MRI
      seemed to be crucial in patients with a risk of LNI <5% as calculated by the BN.
      The presence of ECE, SVI, or pG4 at mp-MRI was found to be an independent
      predictor of LNI by itself.

PMID- 29472630
TI  - Spin-helix Larmor mode.
AB  - A two-dimensional electron gas (2DEG) with equal-strength Rashba and Dresselhaus
      spin-orbit coupling sustains persistent helical spin-wave states, which have
      remarkably long lifetimes. In the presence of an in-plane magnetic field, there
      exist single-particle excitations that have the character of propagating helical
      spin waves. For magnon-like collective excitations, the spin-helix texture
      reemerges as a robust feature, giving rise to a decoupling of spin-orbit and
      electronic many-body effects. We prove that the resulting spin-flip wave
      dispersion is the same as in a magnetized 2DEG without spin-orbit coupling, apart
      from a shift by the spin-helix wave vector. The precessional mode about the
      persistent spin-helix state is shown to have an energy given by the bare Zeeman
      splitting, in analogy with Larmor's theorem. We also discuss ways to observe the
      spin-helix Larmor mode experimentally.

PMID- 29472631
TI  - Enhanced efficiency of crystalline Si solar cells based on kerfless-thin wafers
      with nanohole arrays.
AB  - Several techniques have been proposed for kerfless wafering of thin Si wafers,
      which is one of the most essential techniques for reducing Si material loss in
      conventional wafering methods to lower cell cost. Proton induced exfoliation is
      one of promising kerfless techniques due to the simplicity of the process of
      implantation and cleaving. However, for application to high efficiency solar
      cells, it is necessary to cope with some problems such as implantation damage
      removal and texturing of (111) oriented wafers. This study analyzes the end-of
      range defects at both kerfless and donor wafers and ion cutting sites. Thermal
      treatment and isotropic etching processes allow nearly complete removal of
      implantation damages in the cleaved-thin wafers. Combining laser interference
      lithography and a reactive ion etch process, a facile nanoscale texturing process
      for the kerfless thin wafers of a (111) crystal orientation has been developed.
      We demonstrate that the introduction of nanohole array textures with an optimal
      design and complete damage removal lead to an improved efficiency of 15.2% based
      on the kerfless wafer of a 48 MUm thickness using the standard architecture of
      the Al back surface field.

PMID- 29472632
TI  - African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is
      mono- and di-ubiquitinated and required for viral replication cycle.
AB  - African swine fever virus is the etiological agent of a contagious and fatal
      acute haemorrhagic viral disease for which there are no vaccines or therapeutic
      options. The ASFV encodes for a putative E2 ubiquitin conjugating enzyme (ORF
      I215L) that shows sequence homology with eukaryotic counterparts. In the present
      study, we showed that pI215L acts as an E2-ubiquitin like enzyme in a large range
      of pH values and temperatures, after short incubation times. Further experiments
      revealed that pI215L is polyubiquitinated instead of multi-mono-ubiquitinated and
      Cys85 residue plays an essential role in the transthioesterification reaction. In
      infected cells, I215L gene is transcribed from 2 hours post infection and
      immunoblot analysis confirmed that pI215L is expressed from 4 hpi.
      Immunofluorescence studies revealed that pI215L is recruited to viral factories
      from 8 hpi and a diffuse distribution pattern throughout the nucleus and
      cytoplasm. siRNA studies suggested that pI215L plays a critical role in the
      transcription of late viral genes and viral DNA replication. Altogether, our
      results emphasize the potential use of this enzyme as target for drug and vaccine
      development against ASF.

PMID- 29472633
TI  - Colorectal cancer: Bacterial biofilms and toxins prompt a perfect storm for colon
      cancer.

PMID- 29472634
TI  - Hakai overexpression effectively induces tumour progression and metastasis in
      vivo.
AB  - At early stages of carcinoma progression, epithelial cells undergo a program
      named epithelial-to-mesenchymal transition characterized by the loss of the major
      component of the adherens junctions, E-cadherin, which in consequence causes the
      disruption of cell-cell contacts. Hakai is an E3 ubiquitin-ligase that binds to E
      cadherin in a phosphorylated-dependent manner and induces its degradation; thus
      modulating cell adhesions. Here, we show that Hakai expression is gradually
      increased in adenoma and in different TNM stages (I-IV) from colon
      adenocarcinomas compared to human colon healthy tissues. Moreover, we confirm
      that Hakai overexpression in epithelial cells drives transformation in cells, a
      mesenchymal and invasive phenotype, accompanied by the downregulation of E
      cadherin and the upregulation of N-cadherin, and an increased proliferation and
      an oncogenic potential. More importantly, for the first time, we have studied the
      role of Hakai during cancer progression in vivo. We show that Hakai-transformed
      MDCK cells dramatically induce tumour growth and local invasion in nude mice and
      tumour cells exhibit a mesenchymal phenotype. Furthermore, we have detected the
      presence of micrometastasis in the lung mice, further confirming Hakai role
      during tumour metastasis in vivo. These results lead to the consideration of
      Hakai as a potential new therapeutic target to block tumour development and
      metastasis.

PMID- 29472635
TI  - Nasopharyngeal Pneumococcal Carriage in Nigeria: a two-site, population-based
      survey.
AB  - Changes in nasopharyngeal (NP) carriage of vaccine-type (VT) Streptococcus
      pneumoniae can be used to assess the effectiveness of a pneumococcal conjugate
      vaccine (PCV10). We conducted a baseline carriage survey in rural (Kumbotso,
      Kano) and urban (Pakoto, Ogun) Nigeria. In this cross-sectional study, we
      obtained data on demography, clinical history, risk factors, and took NP swabs
      for pneumococcal culture. We calculated crude and age-standardised carriage
      prevalence and used log-binomial regression to assess risk factors for carriage.
      Among children aged <5 years, 92% (95% CI: 88-95%) and 78% (73-82%),
      respectively, carried any pneumococcus and 48% and 50%, respectively, carried
      PCV10 serotypes. In Kumbotso, carriage prevalence was >40% across all ages. The
      age-standardized prevalence of pneumococcal carriage was 66% in Kumbotso and 40%
      in Pakoto. The most commonly identified serotypes were 19 F, 6 A and 23 F. Risk
      factors for carriage were young age, recent rhinorrhoea, cohabitation with >=2
      children aged <5 years, and sharing a bed with >=2 persons. Pneumococcal carriage
      prevalence is high in this Nigerian population. Persisting prevalence of VT
      carriage in older children and adults suggests that PCV10 introduction in
      children will not eliminate transmission of vaccine serotypes rapidly. High
      vaccine coverage will therefore be required to ensure full protection of
      children.

PMID- 29472636
TI  - CXCL12/CXCR4-Mediated Procollagen Secretion Is Coupled To Cullin-RING Ubiquitin
      Ligase Activation.
AB  - Tissue fibrosis is mediated by the actions of multiple pro-fibrotic proteins that
      can induce myofibroblast phenoconversion through diverse signaling pathways
      coupled predominantly to Smads or MEK/Erk proteins. The TGFbeta/TGFbetaR and
      CXCL12/CXCR4 axes induce myofibroblast phenoconversion independently through
      Smads and MEK/Erk proteins, respectively. To investigate these mechanisms at the
      genetic level, we have now elucidated the TGFbeta/TGFbetaR and CXCL12/CXCR4
      transcriptomes in human fibroblasts. These transcriptomes are largely convergent,
      and up-regulate transcripts encoding proteins known to promote myofibroblast
      phenoconversion. These studies also revealed a molecular signature unique to
      CXCL12/CXCR4 axis activation for COPII vesicle formation, ubiquitination, and
      Golgi/ER localization/targeting. In particular, both CUL3 and KLHL12, key members
      of the Cullin-RING (CRL) ubiquitin ligase family of proteins involved in
      procollagen transport from the ER to the Golgi, were highly up-regulated in
      CXCL12-, but repressed in TGFbeta-, treated cells. Up-regulation of CUL3 and
      KLHL12 was correlated with higher procollagen secretion by CXCL12-treated cells,
      and this affect was ablated upon treatment with inhibitors specific for CXCR4 or
      CUL3 and repressed by TGFbeta/TGFbetaR axis activation. The results of these
      studies show that activation of the CXCL12/CXCR4 axis uniquely facilitates
      procollagen I secretion through a COPII-vesicle mediated mechanism to promote
      production of the ECM characteristic of fibrosis.

PMID- 29472637
TI  - Impact of target interactions on small-molecule drug disposition: an overlooked
      area.

PMID- 29472639
TI  - Transcription Factor Target Gene Network governs the Logical Abstraction Analysis
      of the Synthetic Circuit in Leishmaniasis.
AB  - With the advent of synthetic biology in medicine many synthetic or engineered
      proteins have made their way to therapeutics and diagnostics. In this paper, the
      downstream gene network of CD14-TNF-EGFR pathway in leishmaniasis, a tropical
      disease, is reconstructed. Network analysis showed that NFkB links the signaling
      and gene network, used as a point of intervention through a synthetic circuit
      embedded within the negative autoregulatory feedback loop. A chimeric protein
      kinase C (PKC) is incorporated in the synthetic circuit, under the
      transcriptional regulation of Lac repressor and IPTG, as an inducer. The chimeric
      PKC_zetaalpha via IkappaKb phosphorylation activates NFkappaB, and modulates the
      gene expression from an anti-inflammatory to a pro-inflammatory phenotype in in
      vitro L. major infected macrophage model. This is the first ever report of a
      synthetic device construction in leishmania.

PMID- 29472640
TI  - Ubc9 overexpression and SUMO1 deficiency blunt inflammation after intestinal
      ischemia/reperfusion.
AB  - The intestinal epithelium constitutes a crucial defense to the potentially life
      threatening effects of gut microbiota. However, due to a complex underlying
      vasculature, hypoperfusion and resultant tissue ischemia pose a particular risk
      to function and integrity of the epithelium. The small ubiquitin-like modifier
      (SUMO) conjugation pathway critically regulates adaptive responses to metabolic
      stress and is of particular significance in the gut, as inducible knockout of the
      SUMO-conjugating enzyme Ubc9 results in rapid intestinal epithelial
      disintegration. Here we analyzed the pattern of individual SUMO isoforms in
      intestinal epithelium and investigated their roles in intestinal
      ischemia/reperfusion (I/R) damage. Immunostaining revealed that epithelial
      SUMO2/3 expression was almost exclusively limited to crypt epithelial nuclei in
      unchallenged mice. However, intestinal I/R or overexpression of Ubc9 caused a
      remarkable enhancement of epithelial SUMO2/3 staining along the crypt-villus
      axis. Unexpectedly, a similar pattern was found in SUMO1 knockout mice. Ubc9
      transgenic mice, but also SUMO1 knockout mice were protected from I/R injury as
      evidenced by better preserved barrier function and blunted inflammatory
      responses. PCR array analysis of microdissected villus-tip epithelia revealed a
      specific epithelial contribution to reduced inflammatory responses in Ubc9
      transgenic mice, as key chemotactic signaling molecules such as IL17A were
      significantly downregulated. Together, our data indicate a critical role
      particularly of the SUMO2/3 isoforms in modulating responses to I/R and provide
      the first evidence that SUMO1 deletion activates a compensatory process that
      protects from ischemic damage.

PMID- 29472638
TI  - Unexplored therapeutic opportunities in the human genome.
AB  - A large proportion of biomedical research and the development of therapeutics is
      focused on a small fraction of the human genome. In a strategic effort to map the
      knowledge gaps around proteins encoded by the human genome and to promote the
      exploration of currently understudied, but potentially druggable, proteins, the
      US National Institutes of Health launched the Illuminating the Druggable Genome
      (IDG) initiative in 2014. In this article, we discuss how the systematic
      collection and processing of a wide array of genomic, proteomic, chemical and
      disease-related resource data by the IDG Knowledge Management Center have enabled
      the development of evidence-based criteria for tracking the target development
      level (TDL) of human proteins, which indicates a substantial knowledge deficit
      for approximately one out of three proteins in the human proteome. We then
      present spotlights on the TDL categories as well as key drug target classes,
      including G protein-coupled receptors, protein kinases and ion channels, which
      illustrate the nature of the unexplored opportunities for biomedical research and
      therapeutic development.

PMID- 29472641
TI  - BigR is a sulfide sensor that regulates a sulfur transferase/dioxygenase required
      for aerobic respiration of plant bacteria under sulfide stress.
AB  - To cope with toxic levels of H2S, the plant pathogens Xylella fastidiosa and
      Agrobacterium tumefaciens employ the bigR operon to oxidize H2S into sulfite. The
      bigR operon is regulated by the transcriptional repressor BigR and it encodes a
      bifunctional sulfur transferase (ST) and sulfur dioxygenase (SDO) enzyme, Blh,
      required for H2S oxidation and bacterial growth under hypoxia. However, how Blh
      operates to enhance bacterial survival under hypoxia and how BigR is deactivated
      to derepress operon transcription is unknown. Here, we show that the ST and SDO
      activities of Blh are in vitro coupled and necessary to oxidize sulfide into
      sulfite, and that Blh is critical to maintain the oxygen flux during A.
      tumefaciens respiration when oxygen becomes limited to cells. We also show that
      H2S and polysulfides inactivate BigR leading to operon transcription. Moreover,
      we show that sulfite, which is produced by Blh in the ST and SDO reactions, is
      toxic to Citrus sinensis and that X. fastidiosa-infected plants accumulate
      sulfite and higher transcript levels of sulfite detoxification enzymes,
      suggesting that they are under sulfite stress. These results indicate that BigR
      acts as a sulfide sensor in the H2S oxidation mechanism that allows pathogens to
      colonize plant tissues where oxygen is a limiting factor.

PMID- 29472642
TI  - Role of trace amine-associated receptor 1 in nicotine's behavioral and
      neurochemical effects.
AB  - Nicotine addiction and abuse remains a global health issue. To date, the
      fundamental neurobiological mechanism of nicotine addiction remains incompletely
      understood. Trace amine-associated receptor 1 (TAAR1) is thought to directly
      modulate dopaminergic system and are thought to be a neural substrate underlying
      addictive-like behaviors. We aimed to investigate the role of TAAR1 in nicotine
      addictive-like behaviors. TAAR1 expression after nicotine treatment was evaluated
      by western blotting. c-Fos immunofluorescence and in vivo fast-scan cyclic
      voltammetry were used to examine the activation of brain regions and dopamine
      release, respectively. We then thoroughly and systematically examined the role of
      TAAR1 in mediating nicotine-induced sensitization, nicotine discrimination,
      nicotine self-administration, nicotine demand curve, and the reinstatement of
      nicotine-seeking. Local pharmacological manipulation was conducted to determine
      the role of TAAR1 in the nucleus accumbens (NAcs) in the reinstatement of
      nicotine-seeking. We found that the expression of TAAR1 protein was selectively
      downregulated in the NAc, with no change in either dorsal striatum or prefrontal
      cortex. TAAR1 activation was sufficient to block nicotine-induced c-Fos
      expression in the NAc, while also reducing nicotine-induced dopamine release in
      the NAc. Systemic administration of TAAR1 agonists attenuated the expression and
      development of nicotine-induced sensitization, nicotine self-administration, the
      reinstatement of nicotine-seeking, and increased the elasticity of nicotine
      demand curve, while intra-NAc infusions of a TAAR1 agonist was sufficient to
      attenuate nicotine reinstatement. Moreover, TAAR1-knockout rats showed augmented
      cue-induced and drug-induced reinstatement of nicotine-seeking. These results
      indicated that modulation of TAAR1 activity regulates nicotine addictive-like
      behaviors and TAAR1 represents a novel target towards the treatment of nicotine
      addiction.

PMID- 29472643
TI  - Behavioral and neural markers of cigarette-craving regulation in young-adult
      smokers during abstinence and after smoking.
AB  - Cigarette craving contributes substantially to the maintenance of tobacco use
      disorder. Behavioral strategies to regulate craving may facilitate smoking
      cessation but remain underexplored. We adapted an emotion-regulation strategy,
      using proximal/distal self-positioning, to the context of cigarette craving to
      examine craving regulation in 42, daily smokers (18-25 years old). After
      overnight abstinence from smoking, before and after smoking their first cigarette
      of the day, participants viewed videos of natural scenes presenting young adults
      who were either smoking cigarettes ("smoke") or not ("non-smoke"). Before each
      video, participants were instructed to imagine themselves either immersed in the
      scene ("close") or distanced from it ("far"). They rated their craving after each
      video. Task-based fMRI data are presented for a subsample of participants (N =
      21). We found main effects of smoking, instruction, and video type on craving
      lower ratings after smoking than before, following the "far" vs. "close"
      instructions, and when viewing non-smoke vs. smoke videos. Before smoking,
      "smoke" vs. "non-smoke" videos elicited activation in, orbitofrontal cortex,
      anterior cingulate, lateral parietal cortex, mid-occipital cortex, ventral
      striatum, dorsal caudate, and midbrain. Smoking reduced activation in anterior
      cingulate, left inferior frontal gyrus, and bilateral temporal poles. Activation
      was reduced in the ventral striatum and medial prefrontal cortex after the "far"
      vs. the "close" instruction, suggesting less engagement with the stimuli during
      distancing. The results indicate that proximal/distal regulation strategies
      impact cue-elicited craving, potentially via downregulation of the ventral
      striatum and medial prefrontal cortex, and that smoking during abstinence may
      increase cognitive control capacity during craving regulation.

PMID- 29472645
TI  - A single, extinction-based treatment with a kappa opioid receptor agonist elicits
      a long-term reduction in cocaine relapse.
AB  - Kappa opioid receptor (KOR) agonists have known anti-addiction properties and can
      reduce drug seeking. Their potential for clinical use has largely been daunted by
      their aversive properties mediated through p38 MAPK signaling. Here we examined
      the therapeutic potential of the KOR agonist U50,488 (U50) to reduce cocaine
      seeking in a self-administration model. Following cocaine self-administration and
      7 days of forced home-cage abstinence, rats were administered a single dose of
      U50 (5 mg/kg, i.p.) 30 min prior to the first extinction training session,
      wherein cocaine and the discrete cocaine-paired cues were no longer available.
      U50 reduced cocaine seeking on this first extinction session, but did not alter
      extinction training over subsequent days. 2 weeks after U50 treatment, rats
      underwent a test of cue-induced reinstatement, and rats that had received U50
      reinstated less than controls. Central inhibition of p38 MAPK at the time of U50
      administration prevented its long-term therapeutic effect on reinstatement, but
      not its acute reduction in drug seeking on extinction day 1. The long-term
      therapeutic effect of U50 required operant extinction during U50 exposure,
      extended to cocaine-primed reinstatement, and was not mimicked by another
      aversive drug, lithium chloride (LiCl). These data suggest U50 elicits its long
      term anti-relapse effects through a KOR-p38 MAPK-specific aversive
      counterconditioning of the operant cocaine-seeking response. A single, albeit
      aversive treatment that is able to reduce relapse long-term warrants further
      consideration of the therapeutic potential of KOR agonists in the treatment of
      addiction.

PMID- 29472644
TI  - Effects of COMT genotype and tolcapone on lapses of sustained attention after
      sleep deprivation in healthy young men.
AB  - Tolcapone, a brain penetrant selective inhibitor of catechol-O-methyltransferase
      (COMT) devoid of psychostimulant properties, improves cognition and cortical
      information processing in rested volunteers, depending on the genotype of the
      functional Val158Met polymorphism of COMT. The impact of this common genetic
      variant on behavioral and neurophysiological markers of increased sleep need
      after sleep loss is controversial. Here we investigated the potential usefulness
      of tolcapone to mitigate consequences of sleep deprivation on lapses of sustained
      attention, and tested the hypothesis that dopamine signaling in the prefrontal
      cortex (PFC) causally contributes to neurobehavioral and neurophysiological
      markers of sleep homeostasis in humans. We first quantified in 73 young male
      volunteers the impact of COMT genotype on the evolution of attentional lapses
      during 40 h of extended wakefulness. Subsequently, we tested in an independent
      group of 30 young men whether selective inhibition of COMT activity with
      tolcapone counteracts attentional and neurophysiological markers of elevated
      sleep need in a genotype-dependent manner. Neither COMT genotype nor tolcapone
      affected brain electrical activity in wakefulness and sleep. By contrast, COMT
      genotype and tolcapone modulated the sleep loss-induced impairment of vigilant
      attention. More specifically, Val/Met heterozygotes produced twice as many lapses
      after a night without sleep than Met/Met homozygotes. Unexpectedly, tolcapone
      further deteriorated the sleep loss-induced performance deficits when compared to
      placebo, particularly in Val/Met and Met/Met genotypes. The findings suggest that
      PFC dopaminergic tone regulates sustained attention after sleep loss according to
      an inverse U-shape relationship, independently of neurophysiological markers of
      elevated sleep need.

PMID- 29472647
TI  - Bad science: To fluoridate or not to fluoridate: the saga continues.

PMID- 29472648
TI  - 'It's not the destination, it's the journey that counts!'

PMID- 29472646
TI  - Interaction between noradrenergic and cholinergic signaling in amygdala regulates
      anxiety- and depression-related behaviors in mice.
AB  - Medications that target the noradrenergic system are important therapeutics for
      depression and anxiety disorders. More recently, clinical studies have shown that
      the alpha2-noradrenergic receptor (alpha2AR) agonist guanfacine can decrease
      stress-induced smoking relapse during acute abstinence, suggesting that targeting
      the noradrenergic system may aid in smoking cessation through effects on stress
      pathways in the brain. Acetylcholine (ACh), like the nicotine in tobacco, acts at
      nicotinic acetylcholine receptors (nAChRs) to regulate behaviors related to
      anxiety and depression. We therefore investigated interactions between guanfacine
      and ACh signaling in tests of anxiolytic and antidepressant efficacy in female
      and male C57BL/6J mice, focusing on the amygdala as a potential site of
      noradrenergic/cholinergic interaction. The antidepressant-like effects of
      guanfacine were blocked by shRNA-mediated knockdown of alpha2AR in amygdala.
      Knockdown of the high-affinity beta2 nAChR subunit in amygdala also prevented
      antidepressant-like effects of guanfacine, suggesting that these behavioral
      effects require ACh signaling through beta2-containing nAChRs in this brain area.
      Ablation of NE terminals prevented the anxiolytic- and antidepressant-like
      effects of the nicotinic partial agonist cytisine, whereas administration of the
      cholinesterase antagonist physostigmine induced a depression-like phenotype that
      was not altered by knocking down alpha2AR in the amygdala. These studies suggest
      that ACh and NE have opposing actions on behaviors related to anxiety and
      depression and that cholinergic signaling through beta2-containing nAChRs and
      noradrenergic signaling through alpha2a receptors in neurons of the amygdala are
      critical for regulation of these behaviors.

PMID- 29472649
TI  - Are there good reasons for fluoride labelling of food and drink?
AB  - This opinion piece highlights the importance of controlling systemic fluoride
      intake from food and drink in early childhood to minimise risk of dental
      fluorosis whilst maximising caries prevention; the wide range of fluoride
      contents found in a study of commercially-available food and drinks; and the need
      for comprehensive fluoride labelling on food and drink products in the UK,
      particularly those used by infants and young children.

PMID- 29472650
TI  - Are you passionate about health and social care research?

PMID- 29472652
TI  - Conference report: The Association of Dental Anaesthetists Conference 2017.

PMID- 29472651
TI  - Dentists on film: Ill-informed fish.

PMID- 29472655
TI  - BDA AGMs.

PMID- 29472659
TI  - Erratum.
AB  - This corrects the article DOI: 10.1038/sj.bdj.2018.40.

PMID- 29472661
TI  - Oral surgery: A helpful wisdom tooth.

PMID- 29472662
TI  - A guide to minimally invasive crown lengthening and tooth preparation for
      rehabilitating pink and white aesthetics.
AB  - The rehabilitation of anterior dental aesthetics involves a multitude of
      disciplines, each with its own methodologies for achieving a predefined goal. The
      literature is awash with different techniques for a given predicament, based on
      both scientific credence, as well as empirical clinical judgements. An example is
      crown lengthening for correcting uneven gingival zeniths, increasing clinical
      crown lengths, and therefore, reducing the amount of maxillary gingival display
      that detracts from pleasing pink aesthetics. Many procedures have been advocated
      for rectifying gingival anomalies depending on prevailing clinical scenarios and
      aetiology. This paper presents a minimally invasive technique for crown
      lengthening for short clinical crowns concurrent with excessive maxillary
      gingival display, which is expedient, maintaining the inter-proximal papilla,
      mitigating morbidity, reducing post-operative inflammation, and increasing
      patient comfort. In addition, with a similar ethos, a minimally invasive tooth
      preparation approach is presented for achieving optimal white aesthetics.

PMID- 29472663
TI  - Dental careers: Good preparation.

PMID- 29472665
TI  - yCPD.

PMID- 29472666
TI  - Editorial decisions: Diminishing credibility.

PMID- 29472668
TI  - Pathetic jokes.

PMID- 29472671
TI  - High job satisfaction among orthodontic therapists: a UK workforce survey.

PMID- 29472673
TI  - No studies.

PMID- 29472677
TI  - What do dental codes of ethics and conduct suggest about attitudes to raising
      concerns and self-regulation?
AB  - Background The ability of the dental profession to self-regulate and address poor
      performance or impairment is crucial if practitioners are to demonstrate a public
      commitment to patient safety. Failure of the profession to actively engage in
      this activity is likely to call into question trustworthiness and ability to
      place the interests of patients and the public first.Aim To investigate attitudes
      towards self-regulation and the raising of concerns as expressed through the
      ethical codes of different dental professional and regulatory
      organisations.Method A qualitative review of professional codes of ethics written
      and published by dental associations and regulatory bodies using thematic
      analysis to discern common attitudes and perspectives on self-regulation.Results
      Four main themes were identified; (1) explicit expression of the need to report;
      (2) warning against frivolous reporting; (3) acceptance of reporting being
      difficult and; (4) threshold requiring a professional to report. From these
      themes, common and differing attitudes were then explored.Conclusions This review
      shows that often codes of ethics and practice do discuss an obligation to self
      regulate and raise concerns but that this is accompanied by an anxiety
      surrounding unsubstantiated or malicious reporting. This gives the collective
      guidance a defensive tone and message that may be unhelpful in promoting a
      culture of openness and candour.

PMID- 29472678
TI  - OMFS: Resection of the calcified ligament.

PMID- 29472679
TI  - Paediatric dentistry: North/south divide.

PMID- 29472681
TI  - Dentists on film: Snow Dogs.

PMID- 29472684
TI  - New Associate Editor for BDJ.

PMID- 29472682
TI  - Oral health: Sugar tax doubts.

PMID- 29472685
TI  - Pharmacology: MRONJ risk factor.

PMID- 29472686
TI  - A review of the longevity of effect of botulinum toxin in wrinkle treatments.
AB  - Botulinum toxin is widely used in facial rhytide treatments. The duration of its
      effects influences treatment intervals, cost and convenience to the patient.
      These are key factors in successful aesthetic procedures. A review of the
      literature found that duration of effect was between two and six months, with
      most experiencing loss of maximal contraction for three to four months.
      Treatments may last between three to four months, and occasionally up to six
      months. No specific definition of effectiveness/efficacy has been described and
      used to measure comparable end points. Additional research should help clarify
      the impact of brand, age, gender, ethnicity, repetition of treatment and zinc
      phytase supplementation.

PMID- 29472688
TI  - Regenerative endodontic therapy for managing immature non-vital teeth: a national
      survey of UK paediatric dental specialists and trainees.
AB  - Background Several guidelines have been published advocating the use of
      regenerative endodontic therapy (RET) in managing non-vital immature permanent
      teeth. It is unclear, however, how many UK paediatric dental specialists
      routinely use this technique and their opinion of its outcomes, and barriers to
      its use.Aim To assess the knowledge, experience and the opinion of UK based
      paediatric dental specialists/trainees (UKPDS/T) and practitioners working in the
      capacity of paediatric dental specialists on the use of RET.Design A cross
      sectional study using a 22-item questionnaire was developed using the Bristol
      Online Survey tool and circulated electronically to members of the British
      Society of Paediatric Dentistry between August and November 2016.Results Ninety
      eight UKPDS/T completed the survey. A quarter of respondents (N = 24, 24.5%)
      reported using RET. Reasons cited for not using RET included lack of: training (N
      = 48, 45%), materials (N = 28, 26%), evidence (N = 17, 16%) and suitable cases (N
      = 6, 6%). Different protocols in terms of disinfection, medicaments, scaffolds,
      and obturation material were identified.Conclusions This survey highlights a low
      uptake of RET by current UKPDS and trainees with several barriers identified.
      Deviations from the current RET guidelines were identified. Recommendations
      addressing the use of RET in light of the findings of this survey were made.

PMID- 29472690
TI  - Cisplatin Enhances Hepatitis B Virus Replication and PGC-1alpha Expression
      through Endoplasmic Reticulum Stress.
AB  - Chronic hepatitis B infection remains a serious public health issue worldwide.
      Hepatitis B virus (HBV) reactivation is commonly reported in patients receiving
      anticancer therapy, immunosuppressive therapy, or organ and tissue
      transplantation. However, the precise mechanisms underlying chemotherapeutic
      agent-related HBV reactivation remain unclear. Here, we report that peroxisome
      proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha) plays a
      central role in cisplatin-induced HBV transcription and replication. First,
      cisplatin treatment upregulated the expression levels of PGC-1alpha and
      hepatocyte nuclear factor 4 alpha (HNF-4alpha) in both HBV-replicating cells and
      an HBV-transgenic mouse model. PGC-1alpha coactivates with HNF-4alpha, which
      interacts with a core promoter and enhancer II region of HBV genome, thereby
      promoting HBV production. In contrast, knockdown of PGC-1alpha and HNF-4alpha by
      RNA interference in hepatoma cells reversed HBV activation in response to
      cisplatin. Additionally, PGC-1alpha upregulation depended on cisplatin-mediated
      endoplasmic reticulum (ER) stress. We further observed that the recruitment of
      cyclic AMP-responsive element-binding protein plays a crucial role for PGC-1alpha
      transcriptional activation in cisplatin-treated cells. Finally, pharmacologic
      inhibition of ER stress impaired PGC-1alpha upregulation and HBV production
      induced by cisplatin treatment. These findings demonstrate novel molecular
      mechanisms indicating that ER stress-PGC1alpha signaling pathway plays a critical
      role in cisplatin-evoked HBV reactivation.

PMID- 29472692
TI  - Unbiased Spontaneous Solar Fuel Production using Stable LaFeO3 Photoelectrode.
AB  - Photoelectrochemical (PEC) water splitting to produce solar fuel (hydrogen) has
      long been considered as the Holy Grail to a carbon-free hydrogen economy. The PEC
      concept to produce solar fuel is to emulate the natural photosynthesis using man
      made materials. The bottle-neck in realising the concept practically has been the
      difficulty in identifying stable low-cost semiconductors that meet the
      thermodynamic and kinetic criteria for photoelectrolysis. We have fabricated a
      novel p-type LaFeO3 photoelectrode using an inexpensive and scalable spray
      pyrolysis method. Our nanostructured LaFeO3 photoelectrode results in spontaneous
      hydrogen evolution from water without any external bias applied. Moreover, the
      photoelectrode has a faradaic efficiency of 30% and showed excellent stability
      over 21 hours. From optical and impedance data, the constructed band diagram
      showed that LaFeO3 can straddle the water redox potential with the conduction
      band at -1.11 V above the reduction potential of hydrogen. We have fabricated a
      low cost LaFeO3 photoelectrode that can spontaneously produce hydrogen from water
      using sunlight, making it a strong future candidate for renewable hydrogen
      generation.

PMID- 29472691
TI  - A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy.
AB  - It is assumed that anti-CTLA-4 antibodies cause tumor rejection by blocking
      negative signaling from B7-CTLA-4 interactions. Surprisingly, at concentrations
      considerably higher than plasma levels achieved by clinically effective dosing,
      the anti-CTLA-4 antibody Ipilimumab blocks neither B7 trans-endocytosis by CTLA-4
      nor CTLA-4 binding to immobilized or cell-associated B7. Consequently, Ipilimumab
      does not increase B7 on dendritic cells (DCs) from either CTLA4 gene humanized
      (Ctla4 h/h ) or human CD34+ stem cell-reconstituted NSGTM mice. In Ctla4 h/m mice
      expressing both human and mouse CTLA4 genes, anti-CTLA-4 antibodies that bind to
      human but not mouse CTLA-4 efficiently induce Treg depletion and Fc receptor
      dependent tumor rejection. The blocking antibody L3D10 is comparable to the non
      blocking Ipilimumab in causing tumor rejection. Remarkably, L3D10 progenies that
      lose blocking activity during humanization remain fully competent in inducing
      Treg depletion and tumor rejection. Anti-B7 antibodies that effectively block CD4
      T cell activation and de novo CD8 T cell priming in lymphoid organs do not
      negatively affect the immunotherapeutic effect of Ipilimumab. Thus, clinically
      effective anti-CTLA-4 mAb causes tumor rejection by mechanisms that are
      independent of checkpoint blockade but dependent on the host Fc receptor. Our
      data call for a reappraisal of the CTLA-4 checkpoint blockade hypothesis and
      provide new insights for the next generation of safe and effective anti-CTLA-4
      mAbs.

PMID- 29472693
TI  - A new allele of the Brachytic2 gene in maize can efficiently modify plant
      architecture.
AB  - The applications of semi-dwarf genes such as sd1 and Rht1 in rice and wheat
      resulted in the first "green revolution" in the 1960s. However, such semi-dwarf
      genes that can efficiently reduce plant stature and have few negative yield
      traits have not yet been identified in maize. In this study, a new allele of
      Brachytic2 gene (qpa1) encoding P-glycoprotein was rapidly fine-mapped using a
      modified method. The qpa1, containing a 241-bp deletion in the last exon, had no
      negative effect on yield, but greatly modified the plant architecture including
      significantly reduced plant height and ear height, increased stalk diameter and
      erected leaf. A common variant similar to maize qpa1 was also present in the
      sorghum orthologous dw3 locus. Comparative RNA-seq analysis next showed 99
      differentially co-expressed genes affected by Br2 in maize and dw3 in sorghum,
      including four plant height genes D3, BAK1, Actin7 and Csld1, which are involved
      in gibberellin and brassinosteroid biosynthesis, auxin transport and cellulose
      synthesis. The qpa1 can be applied to efficiently modify plant stature in maize
      and in combination with D3, BAK1, Actin7, Csld1 and the other 95 differentially
      co-expressed genes, can be edited using new genomic editing tools for further
      applications and studies.

PMID- 29472694
TI  - Improving accuracies of genomic predictions for drought tolerance in maize by
      joint modeling of additive and dominance effects in multi-environment trials.
AB  - Breeding for drought tolerance is a challenging task that requires costly,
      extensive, and precise phenotyping. Genomic selection (GS) can be used to
      maximize selection efficiency and the genetic gains in maize (Zea mays L.)
      breeding programs for drought tolerance. Here, we evaluated the accuracy of
      genomic selection (GS) using additive (A) and additive + dominance (AD) models to
      predict the performance of untested maize single-cross hybrids for drought
      tolerance in multi-environment trials. Phenotypic data of five drought tolerance
      traits were measured in 308 hybrids along eight trials under water-stressed (WS)
      and well-watered (WW) conditions over two years and two locations in Brazil.
      Hybrids' genotypes were inferred based on their parents' genotypes (inbred lines)
      using single-nucleotide polymorphism markers obtained via genotyping-by
      sequencing. GS analyses were performed using genomic best linear unbiased
      prediction by fitting a factor analytic (FA) multiplicative mixed model. Two
      cross-validation (CV) schemes were tested: CV1 and CV2. The FA framework allowed
      for investigating the stability of additive and dominance effects across
      environments, as well as the additive-by-environment and the dominance-by
      environment interactions, with interesting applications for parental and hybrid
      selection. Results showed differences in the predictive accuracy between A and AD
      models, using both CV1 and CV2, for the five traits in both water conditions. For
      grain yield (GY) under WS and using CV1, the AD model doubled the predictive
      accuracy in comparison to the A model. Through CV2, GS models benefit from
      borrowing information of correlated trials, resulting in an increase of 40% and
      9% in the predictive accuracy of GY under WS for A and AD models, respectively.
      These results highlight the importance of multi-environment trial analyses using
      GS models that incorporate additive and dominance effects for genomic predictions
      of GY under drought in maize single-cross hybrids.

PMID- 29472695
TI  - Deficiency of a pyrroline-5-carboxylate reductase produces the yellowish green
      cocoon 'Ryokuken' of the silkworm, Bombyx mori.
AB  - The silkworm cocoon colour has attracted researchers involved in genetics,
      physiology and ecology for a long time. 'Ryokuken' cocoons are yellowish green in
      colour due to unusual flavonoids, prolinylflavonols, while 'Sasamayu' cocoons are
      light green and contain only simple flavonol glucosides. We found a novel gene
      associated with the cocoon colour change resulting from a change in flavonoid
      composition and named it Lg (light green cocoon). In the middle silk glands of
      the + Lg /+ Lg larvae, 1-pyrroline-5-carboxylic acid (P5C) was found to
      accumulate due to a decrease in the activity of pyrroline-5-carboxylate reductase
      (P5CR), an enzyme reducing P5C to proline. Sequence analysis of BmP5CR1, the
      candidate gene for Lg, revealed a 1.9 kb insertion and a 4 bp deletion within the
      1st intron, a 97 bp deletion within the 4th intron, and a > 300 bp insertion
      within the 3'-UTR, in addition to two amino acid changes on exons 3 and 4 in + Lg
      /+ Lg compared to Lg/Lg. Decreased expression of BmP5CR1 was observed in all of
      the investigated tissues, including the middle silk glands in + Lg /+ Lg , which
      was probably caused by structural changes in the intronic regions of BmP5CR1.
      Furthermore, a BmP5CR1 knockout strain exhibited a yellowish green cocoon with
      the formation of prolinylflavonols. These results indicate that the yellowish
      green cocoon is produced by a BmP5CR1 deficiency. To our knowledge, this is the
      first report showing that the defect of an enzyme associated with intermediate
      metabolism promotes the conjugation of phytochemicals derived from foods with
      endogenously accumulating metabolites in animal tissues.

PMID- 29472696
TI  - Topical ciclosporin 1 mg/ml for chronic ocular surface inflammation in children.

PMID- 29472697
TI  - Comment on: 'Immediate IOP elevation after transscleral cyclophotocoagulation'.

PMID- 29472698
TI  - The junior doctor view of undergraduate ophthalmology education.

PMID- 29472699
TI  - Treatment of intraocular spread of acanthamoeba after tectonic corneal graft in
      acanthamoeba keratitis.

PMID- 29472700
TI  - Neuroprotective agents in the management of glaucoma.
AB  - Glaucoma is an optic neuropathy, specifically a neurodegenerative disease
      characterized by loss of retinal ganglion cells (RGCs) and their axons. The
      pathogenesis of RGC loss in glaucoma remains incompletely understood and a broad
      range of possible mechanisms have been implicated. Clinical evidence indicates
      that lowering intraocular pressure (IOP) does not prevent progression in all
      patients; therefore, risk factors other than those related to IOP are involved in
      the disease. The need for alternative, non-IOP-lowering treatments focused at
      preventing progression, that is, neuroprotectants, has become of interest to both
      the patient and the physician. Experimental evidence accumulated during the past
      two decades lend a great deal of support to molecules endowed with
      neuroprotective features. However, translation to the clinic of the latter drugs
      results unsuccessful mostly because of the lack of reliable in vivo measure of
      retinal damage, thus hampering the good therapeutic potential of neuroprotective
      agents given alone or as adjuvant therapy to IOP-lowering agents. Further
      research effort is needed to better understand the mechanisms involved in
      glaucoma and the means to translate into clinic neuroprotective drugs.

PMID- 29472701
TI  - Akkermansia muciniphila-derived extracellular vesicles influence gut permeability
      through the regulation of tight junctions.
AB  - The gut microbiota has an important role in the gut barrier, inflammation and
      metabolic functions. Studies have identified a close association between the
      intestinal barrier and metabolic diseases, including obesity and type 2 diabetes
      (T2D). Recently, Akkermansia muciniphila has been reported as a beneficial
      bacterium that reduces gut barrier disruption and insulin resistance. Here we
      evaluated the role of A. muciniphila-derived extracellular vesicles (AmEVs) in
      the regulation of gut permeability. We found that there are more AmEVs in the
      fecal samples of healthy controls compared with those of patients with T2D. In
      addition, AmEV administration enhanced tight junction function, reduced body
      weight gain and improved glucose tolerance in high-fat diet (HFD)-induced
      diabetic mice. To test the direct effect of AmEVs on human epithelial cells,
      cultured Caco-2 cells were treated with these vesicles. AmEVs decreased the gut
      permeability of lipopolysaccharide-treated Caco-2 cells, whereas Escherichia coli
      derived EVs had no significant effect. Interestingly, the expression of occludin
      was increased by AmEV treatment. Overall, these results imply that AmEVs may act
      as a functional moiety for controlling gut permeability and that the regulation
      of intestinal barrier integrity can improve metabolic functions in HFD-fed mice.

PMID- 29472702
TI  - Inhibition of TNFalpha-interacting protein alpha (Tipalpha)-associated gastric
      carcinogenesis by BTG2/TIS21 via downregulating cytoplasmic nucleolin expression.
AB  - To understand the regulation of Helicobacter pylori (H. pylori)-associated
      gastric carcinogenesis, we examined the effect of B-cell translocation gene 2
      (BTG2) expression on the biological activity of Tipalpha, an oncoprotein secreted
      from H. pylori. BTG2, the human ortholog of mouse TIS21 (BTG2/TIS21), has been
      reported to be a primary response gene that is transiently expressed in response
      to various stimulations. Here, we report that BTG2 is constitutively expressed in
      the mucous epithelium and parietal cells of the gastric gland in the stomach.
      Expression was increased in the mucous epithelium following H. pylori infection
      in contrast to its loss in human gastric adenocarcinoma. Indeed, adenoviral
      transduction of BTG2/TIS21 significantly inhibited Tipalpha activity in MKN-1 and
      MGT-40, human and mouse gastric cancer cells, respectively, thereby
      downregulating tumor necrosis factor-alpha (TNFalpha) expression and Erk1/2
      phosphorylation by reducing expression of nucleolin, a Tipalpha receptor.
      Chromatin immunoprecipitation proved that BTG2/TIS21 inhibited Sp1 expression and
      its binding to the promoter of the nucleolin gene. In addition, BTG2/TIS21
      expression significantly reduced membrane-localized nucleolin expression in
      cancer cells, and the loss of BTG2/TIS21 expression induced cytoplasmic nucleolin
      availability in gastric cancer tissues, as evidenced by immunoblotting and
      immunohistochemistry. Higher expression of BTG2 and lower expression of nucleolin
      were accompanied with better overall survival of poorly differentiated gastric
      cancer patients. This is the first report showing that BTG2/TIS21 inhibits
      nucleolin expression via Sp1 binding, which might be associated with the
      inhibition of H. pylori-induced carcinogenesis. We suggest that BTG2/TIS21 is a
      potential inhibitor of nucleolin in the cytoplasm, leading to inhibition of
      carcinogenesis after H. pylori infection.

PMID- 29472704
TI  - Neurodegenerative disease: C9orf72 insufficiency cooperates with toxic repeat
      peptides to kill neurons.

PMID- 29472705
TI  - Neurodegenerative disease: Gene expression in aged microglia is related to
      neurodegenerative disease.

PMID- 29472703
TI  - Suppression of the ERK-SRF axis facilitates somatic cell reprogramming.
AB  - The molecular mechanism underlying the initiation of somatic cell reprogramming
      into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we
      generated single-cell-derived clones by using a combination of drug-inducible
      vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single
      cell expansion strategy. This system achieved a high reprogramming efficiency
      after metabolic and epigenetic remodeling. Functional analyses of the cloned
      cells revealed that extracellular signal-regulated kinase (ERK) signaling was
      downregulated at an early stage of reprogramming and that its inhibition was a
      driving force for iPSC formation. Among the reprogramming factors, Myc
      predominantly induced ERK suppression. ERK inhibition upregulated the conversion
      of somatic cells into iPSCs through concomitant suppression of serum response
      factor (SRF). Conversely, SRF activation suppressed the reprogramming induced by
      ERK inhibition and negatively regulated embryonic pluripotency by inducing
      differentiation via upregulation of immediate early genes, such as c-Jun, c-Fos
      and EGR1. These data reveal that suppression of the ERK-SRF axis is an initial
      molecular event that facilitates iPSC formation and may be a useful surrogate
      marker for cellular reprogramming.

PMID- 29472707
TI  - Concern for mortality in the neonatal intensive care unit (NICU): parent and
      physician perspectives.
AB  - OBJECTIVE: The objectives of this study are as follows: (1) to determine the
      incidence of parental concern for mortality (PCM) and any potential predictors
      for it among parents of infants admitted to the Neonatal Intensive Care Unit
      (NICU), and (2) to explore physicians' perspectives with respect to PCM in the
      NICU and to examine current practices of addressing it. STUDY DESIGN: Separate
      questionnaires were distributed to members of the AAP Section on Perinatal
      Neonatal Medicine District I and to NICU parents post discharge, to gather
      perspectives from each group. A chi2-analysis and linear regression were
      performed. RESULTS: Response rate was 29% for the physician survey and 63% for
      the parent survey. Physician respondents believed that PCM increased with
      decreasing gestational age (GA) and reported having fewer discussions with
      parents of older infants about PCM. Parental report of PCM incidence was 48%
      overall. PCM was not associated with GA. PCM was associated with infant length of
      stay and occurrence of at least one discussion about PCM with physicians. Fifty
      three percent of parents reported never having a discussion regarding PCM.
      CONCLUSION: Although physicians believe that PCM increases with decreasing GA,
      parental report suggests that PCM is not associated with GA. Parents of full-term
      infants in particular may experience more PCM and desire for discussion than is
      currently recognized.

PMID- 29472706
TI  - Atm reactivation reverses ataxia telangiectasia phenotypes in vivo.
AB  - Hereditary deficiencies in DNA damage signaling are invariably associated with
      cancer predisposition, immunodeficiency, radiation sensitivity, gonadal
      abnormalities, premature aging, and tissue degeneration. ATM kinase has been
      established as a central player in DNA double-strand break repair and its
      deficiency causes ataxia telangiectasia, a rare, multi-system disease with no
      cure. So ATM represents a highly attractive target for the development of novel
      types of gene therapy or transplantation strategies. Atm tamoxifen-inducible
      mouse models were generated to explore whether Atm reconstitution is able to
      restore Atm function in an Atm-deficient background. Body weight,
      immunodeficiency, spermatogenesis, and radioresistance were recovered in
      transgenic mice within 1 month from Atm induction. Notably, life span was doubled
      after Atm restoration, mice were protected from thymoma and no cerebellar defects
      were observed. Atm signaling was functional after DNA damage in vivo and in
      vitro. In summary, we propose a new Atm mouse model to investigate novel
      therapeutic strategies for ATM activation in ataxia telangiectasia disease.

PMID- 29472708
TI  - No question too small: development of a question prompt list for parents of
      critically ill infants.
AB  - OBJECTIVE: To develop a question prompt list tailored to the needs of parents of
      critically ill infants at risk of neurodevelopmental impairment. STUDY DESIGN:
      Question content was derived from audio-recorded neonatal intensive care unit
      family meetings and interviews with parents of infants treated with therapeutic
      hypothermia. Question content was refined using clinician focus groups.
      Acceptability testing was performed with parents and clinicians caring for
      infants in the neonatal intensive care unit. RESULTS: All clinicians and parents
      found the QPL content acceptable. Parents universally endorsed that the question
      prompt list was useful to them and would help them prepare for a meeting with
      their infant's healthcare team. CONCLUSION: This question prompt list, designed
      for parents of critically ill infants, is acceptable to parents and clinicians,
      and can be used in the acute neonatal course to facilitate parent engagement in
      family meetings.

PMID- 29472709
TI  - Splanchnic NIRS monitoring in neonatal care: rationale, current applications and
      future perspectives.
AB  - Near infrared spectroscopy (NIRS) provides a non-invasive, continuous monitoring
      of regional tissue oxygenation. NIRS assessment of neonatal splanchnic
      oxygenation (SrSO2) has gained increasing interest over the last decade, as local
      hypoxia and ischemia underlie the most feared gut complications in neonates.
      Current literature provides encouraging evidence in support of SrSO2 reliability
      in detecting mesenteric hemodynamic changes related to various physiological and
      pathological conditions in-term and preterm infants. Even so, while splanchnic
      NIRS monitoring looks promising for investigating gut physiopathology in research
      settings, further studies are needed to evaluate its feasibility as a routine
      monitoring tool in neonatal care and to investigate its potential role in
      clinical decision making. After a brief introduction to NIRS technical
      principles, this review aims to provide a complete overview of current neonatal
      applications for splanchnic NIRS monitoring, to discuss its possible limitations
      and to suggest future directions for research and clinical applications.

PMID- 29472710
TI  - Genetics: Functional link to hyperphagia in PWS.

PMID- 29472711
TI  - Metabolism: The small intestine - a new player in fructose metabolism.

PMID- 29472713
TI  - Adipose tissue: TBK1 at the crossroad of signalling pathways.

PMID- 29472712
TI  - Direct effects of thyroid hormones on hepatic lipid metabolism.
AB  - It has been known for a long time that thyroid hormones have prominent effects on
      hepatic fatty acid and cholesterol synthesis and metabolism. Indeed,
      hypothyroidism has been associated with increased serum levels of triglycerides
      and cholesterol as well as non-alcoholic fatty liver disease (NAFLD). Advances in
      areas such as cell imaging, autophagy and metabolomics have generated a more
      detailed and comprehensive picture of thyroid-hormone-mediated regulation of
      hepatic lipid metabolism at the molecular level. In this Review, we describe and
      summarize the key features of direct thyroid hormone regulation of lipogenesis,
      fatty acid beta-oxidation, cholesterol synthesis and the reverse cholesterol
      transport pathway in normal and altered thyroid hormone states. Thyroid hormone
      mediates these effects at the transcriptional and post-translational levels and
      via autophagy. Given these potentially beneficial effects on lipid metabolism, it
      is possible that thyroid hormone analogues and/or mimetics might be useful for
      the treatment of metabolic diseases involving the liver, such as
      hypercholesterolaemia and NAFLD.

PMID- 29472714
TI  - Oncogene-induced senescence mediated by c-Myc requires USP10 dependent
      deubiquitination and stabilization of p14ARF.
AB  - Oncogene-induced senescence (OIS) is a critical tumor-suppressor mechanism, which
      prevents hyper-proliferation and transformation of cells. c-Myc promotes OIS
      through the transcriptional activation of p14ARF followed by p53 activation.
      Although the oncogene-mediated transcriptional regulation of p14ARF has been well
      addressed, the post-translational modification of p14ARF regulated by oncogenic
      stress has yet to be investigated. Here, we found that c-Myc increased p14ARF
      protein stability by inducing the transcription of ubiquitin-specific protease 10
      (USP10). USP10, in turn, mediated the deubiquitination of p14ARF, preventing its
      proteasome-dependent degradation. USP10-null mouse embryonic fibroblasts and
      human primary cells depleted of USP10 bypassed c-Myc-induced senescence via the
      destabilization of p14ARF, and these cells displayed accelerated hyper
      proliferation and transformation. Clinically the c-Myc-USP10-p14ARF axis was
      disrupted in non-small cell lung cancer patients, resulting in significantly
      worse overall survival. Our studies indicate that USP10 induced by c-Myc has a
      crucial role in OIS by maintaining the stability of key tumor suppressor p14ARF.

PMID- 29472715
TI  - DeSUMOylation switches Kaiso from activator to repressor upon hyperosmotic
      stress.
AB  - Kaiso is a member of the BTB/POZ zinc finger family, which is involved in cancer
      progression, cell cycle control, apoptosis, and WNT signaling. Depending on
      promoter context, it may function as either a transcriptional repressor or
      activator. Previous studies found that Kaiso might be SUMOylated due to heat
      shock, but the biological significance of Kaiso SUMOylation is unclear. Here, we
      find that K42 is the only amino acid within Kaiso that is modified with SUMO.
      Kaiso is monoSUMOylated at lysine 42 in cell lines of kidney origin under normal
      physiological conditions. SUMOylated Kaiso can activate transcription from
      exogenous methylated promoters, wherein the deSUMOylated form of the protein kept
      the ability to be a repressor. Rapid Kaiso deSUMOylation occurs in response to
      hyperosmotic stress and is reversible upon return to an isotonic environment.
      DeSUMOylation occurs within minutes in HEK293 cells treated with 100 mM NaCl and
      relaxes in 3 h even in a salt-containing medium. Genomic editing of Kaiso by
      conversion of K42 into R42 (K42R) in HEK293 cells that resulted in fully
      deSUMOylated endogenous protein led to misregulation of genes associated with ion
      transport, blood pressure, and the immune response. TRIM25 was significantly
      repressed in two K42R HEK293 clones. By a series of rescue experiments with K42R
      and KO HEK293 cells, we show that TRIM25 is a direct transcriptional target for
      Kaiso. In the absence of Kaiso, the level of TRIM25 is insensitive to
      hyperosmotic stress. Extending our observations to animal models, we show that in
      response to a high salt diet, Kaiso knockout mice are characterized by
      significantly higher blood pressure increases when compared to wild-type animals.
      Thus, we propose a novel biological role for Kaiso in the regulation of
      homeostasis.

PMID- 29472716
TI  - PD-1 is required to maintain stem cell properties in human dental pulp stem
      cells.
AB  - Programmed cell death-1 (PD-1) belongs to an inhibitory signaling pathway capable
      of maintaining central and peripheral immune tolerance. Blockage of PD-1 has been
      identified as a promising immunotherapeutic approach for cancer and chronic
      infectious diseases. However, it is unknown whether PD-1 pathway regulates stem
      cell function. It is generally believed that mesenchymal stem cells (MSCs)
      produce PD-1 ligand, but fail to express PD-1. In this study, we show that neural
      crest-derived MSCs from dental pulp (MSC-DP), but not MSCs from bone marrow,
      expressed PD-1. Knocking down PD-1 expression in MSC-DP results in a
      significantly reduced capacity for cell proliferation and accelerated
      multipotential differentiation. Mechanistically, we show that PD-1 regulates a
      SHP2/ERK/Notch cascade to maintain proliferation and a SHP2/ERK/beta-catenin
      cascade to inhibit osteo-/odontogenic differentiation. This study indicates that
      PD-1 is a key surface molecule controlling cell proliferation and multipotential
      differentiation of MSC-DP. Through regulating PD-1/SHP2/ERK signaling, we can
      significantly improve the quality and quantity of culture-expanded MSC-DP for
      potential clinical therapies.

PMID- 29472717
TI  - Revised cytogenetic risk stratification in primary myelofibrosis: analysis based
      on 1002 informative patients.
AB  - Current cytogenetic risk stratification in primary myelofibrosis (PMF) is two
      tiered: 'favorable' and 'unfavorable'. Recent studies have suggested prognostic
      heterogeneity within the unfavorable risk category. In 1002 consecutive patients,
      we performed stepwise analysis of impact on survival from individual and
      prognostically ordered cytogenetic abnormalities, leading to a revised three
      tiered risk model: 'very high risk (VHR)'-single/multiple abnormalities of -7,
      i(17q), inv(3)/3q21, 12p-/12p11.2, 11q-/11q23, or other autosomal trisomies not
      including + 8/ + 9 (e.g., +21, +19); 'favorable'-normal karyotype or sole
      abnormalities of 13q-, +9, 20q-, chromosome 1 translocation/duplication or sex
      chromosome abnormality including -Y; 'unfavorable'-all other abnormalities.
      Median survivals for VHR (n = 75), unfavorable (n = 190) and favorable (n = 737)
      risk categories were 1.2 (HR 3.8, 95% CI 2.9-4.9), 2.9 (HR 1.7, 95% CI 1.4-2.0)
      and 4.4 years and survival impact was independent of clinically derived
      prognostic systems, driver and ASXL1/SRSF2 mutations. The revised model was also
      effective in predicting leukemic transformation: HRs (95% CI) were 4.4 (2.0-9.4)
      for VHR and 2.0 (1.2-3.4) for unfavorable. The impact of driver mutations on
      survival was confined to favorable and that of ASXL1/SRSF2 mutations to
      favorable/unfavorable cytogenetic risk categories. The current study clarifies
      the prognostic hierarchy of genetic risk factors in PMF and provides a more
      refined three-tiered cytogenetic risk model.

PMID- 29472719
TI  - Epigenetic heterogeneity affects the risk of relapse in children with
      t(8;21)RUNX1-RUNX1T1-rearranged AML.
AB  - The somatic translocation t(8;21)(q22;q22)/RUNX1-RUNX1T1 is one of the most
      frequent rearrangements found in children with standard-risk acute myeloid
      leukemia (AML). Despite the favorable prognostic role of this aberration, we
      recently observed a higher than expected frequency of relapse. Here, we employed
      an integrated high-throughput approach aimed at identifying new biological
      features predicting relapse among 34 t(8;21)-rearranged patients. We found that
      the DNA methylation status of patients who suffered from relapse was peculiarly
      different from that of children maintaining complete remission. The epigenetic
      signature, made up of 337 differentially methylated regions, was then integrated
      with gene and protein expression profiles, leading to a network, where cell-to
      cell adhesion and cell-motility pathways were found to be aberrantly activated in
      relapsed patients. We identified most of these factors as RUNX1-RUNX1T1 targets,
      with Ras Homolog Family Member (RHOB) overexpression being the core of this
      network. We documented how RHOB re-organized the actin cytoskeleton through its
      downstream ROCK-LIMK-COFILIN axis: this increases blast adhesion by stress fiber
      formation, and reduces mitochondrial apoptotic cell death after chemotherapy
      treatment. Altogether, our data show an epigenetic heterogeneity within t(8;21)
      rearranged AML patients at diagnosis able to influence the program of the
      chimeric transcript, promoting blast re-emergence and progression to relapse.

PMID- 29472718
TI  - Pharmacologic inhibition of STAT5 in acute myeloid leukemia.
AB  - The transcription factor STAT5 is an essential downstream mediator of many
      tyrosine kinases (TKs), particularly in hematopoietic cancers. STAT5 is activated
      by FLT3-ITD, which is a constitutively active TK driving the pathogenesis of
      acute myeloid leukemia (AML). Since STAT5 is a critical mediator of diverse
      malignant properties of AML cells, direct targeting of STAT5 is of significant
      clinical value. Here, we describe the development and preclinical evaluation of a
      novel, potent STAT5 SH2 domain inhibitor, AC-4-130, which can efficiently block
      pathological levels of STAT5 activity in AML. AC-4-130 directly binds to STAT5
      and disrupts STAT5 activation, dimerization, nuclear translocation, and STAT5
      dependent gene transcription. Notably, AC-4-130 substantially impaired the
      proliferation and clonogenic growth of human AML cell lines and primary FLT3-ITD+
      AML patient cells in vitro and in vivo. Furthermore, AC-4-130 synergistically
      increased the cytotoxicity of the JAK1/2 inhibitor Ruxolitinib and the p300/pCAF
      inhibitor Garcinol. Overall, the synergistic effects of AC-4-130 with TK
      inhibitors (TKIs) as well as emerging treatment strategies provide new
      therapeutic opportunities for leukemia and potentially other cancers.

PMID- 29472720
TI  - CAR T-cells targeting FLT3 have potent activity against FLT3-ITD+ AML and act
      synergistically with the FLT3-inhibitor crenolanib.
AB  - FMS-like tyrosine kinase 3 (FLT3) is a transmembrane protein expressed on normal
      hematopoietic stem and progenitor cells (HSC) and retained on malignant blasts in
      acute myeloid leukemia (AML). We engineered CD8+ and CD4+ T-cells expressing a
      FLT3-specific chimeric antigen receptor (CAR) and demonstrate they confer potent
      reactivity against AML cell lines and primary AML blasts that express either wild
      type FLT3 or FLT3 with internal tandem duplication (FLT3-ITD). We also show that
      treatment with the FLT3-inhibitor crenolanib leads to increased surface
      expression of FLT3 specifically on FLT3-ITD+ AML cells and consecutively,
      enhanced recognition by FLT3-CAR T-cells in vitro and in vivo. As anticipated, we
      found that FLT3-CAR T-cells recognize normal HSCs in vitro and in vivo, and
      disrupt normal hematopoiesis in colony-formation assays, suggesting that adoptive
      therapy with FLT3-CAR T-cells will require subsequent CAR T-cell depletion and
      allogeneic HSC transplantation to reconstitute the hematopoietic system.
      Collectively, our data establish FLT3 as a novel CAR target in AML with
      particular relevance in high-risk FLT3-ITD+ AML. Further, our data provide the
      first proof-of-concept that CAR T-cell immunotherapy and small molecule
      inhibition can be used synergistically, as exemplified by our data showing
      superior antileukemia efficacy of FLT3-CAR T-cells in combination with
      crenolanib.

PMID- 29472722
TI  - Chromothripsis in acute myeloid leukemia: biological features and impact on
      survival.
AB  - Chromothripsis is a one-step genome-shattering catastrophe resulting from
      disruption of one or few chromosomes in multiple fragments and consequent random
      rejoining and repair. This study defines incidence of chromothripsis in 395 newly
      diagnosed adult acute myeloid leukemia (AML) patients from three institutions,
      its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array
      (Affymetrix(r)) were performed on all samples. We detected chromothripsis with a
      custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher
      age (p = 0.002), ELN high risk (HR) (p < 0.001), lower white blood cell (WBC)
      count (p = 0.040), TP53 loss, and/or mutations (p < 0.001) while FLT3 (p =
      0.025), and NPM1 (p = 0.032) mutations were mutually exclusive with
      chromothripsis. Chromothripsis-positive patients showed a worse overall survival
      (OS) (p < 0.001) compared with HR patients (p = 0.011) and a poor prognosis in a
      COX-HR optimal regression model. Chromothripsis presented the hallmarks of
      chromosome instability [i.e., TP53 alteration, 5q deletion, higher mean of copy
      number alteration (CNA), complex karyotype, alterations in DNA repair, and cell
      cycle] and focal deletions on chromosomes 4, 7, 12, 16, and 17. CBA. FISH showed
      that chromothripsis is associated with marker, derivative, and ring chromosomes.
      In conclusion, chromothripsis frequently occurs in AML (6.6%) and influences
      patient prognosis and disease biology.

PMID- 29472723
TI  - Flow-cytometric vs. -morphologic assessment of remission in childhood acute
      lymphoblastic leukemia: a report from the Children's Oncology Group (COG).
AB  - Minimal residual disease (MRD) after initial therapy is integral to risk
      stratification in B-precursor and T-precursor acute lymphoblastic leukemia (B
      ALL, T-ALL). Although MRD determines depth of remission, remission remains
      defined by morphology. We determined the outcomes of children with discordant
      assessments of remission by morphology vs. flow cytometry using patients age 1
      30.99 years enrolled on Children's Oncology Group ALL trials who underwent bone
      marrow assessment at the end of induction (N = 9350). Morphologic response was
      assessed locally as M1 (<5% lymphoblasts; remission), M2 (5-25%), or M3 (>25%).
      MRD was centrally measured by flow cytometry. Overall, 19.8% of patients with
      M2/M3 morphology had MRD < 5%. M1 with MRD >= 5% was less common in B-ALL (0.9%)
      than T-ALL (6.9%; p < 0.0001). In B-ALL, M1/MRD >= 5% was associated with
      superior 5-year event-free survival (EFS) than M2/MRD >= 5% (59.1% +/- 6.5% vs.
      39.1% +/- 7.9%; p = 0.009), but was inferior to M1/MRD < 5% (87.1% +/- 0.4%; p <
      0.0001). MRD levels were higher in M2/MRD >= 5% than M1/MRD >= 5% patients. In T
      ALL, EFS was not significantly different between M1/MRD >= 5% and M2/MRD >= 5%.
      Patients with morphologic remission but MRD >= 5% have outcomes similar to those
      who fail to achieve morphological remission, and significantly inferior to those
      with M1 marrows and concordant MRD, suggesting that flow cytometry should augment
      the definition of remission in ALL.

PMID- 29472724
TI  - Persistence of pre-leukemic clones during first remission and risk of relapse in
      acute myeloid leukemia.
AB  - Some patients with acute myeloid leukemia (AML) who are in complete remission
      after induction chemotherapy harbor persisting pre-leukemic clones, carrying a
      subset of leukemia-associated somatic mutations. There is conflicting evidence on
      the prognostic relevance of these clones for AML relapse. Here, we characterized
      paired pre-treatment and remission samples from 126 AML patients for mutations in
      68 leukemia-associated genes. Fifty patients (40%) retained >=1 mutation during
      remission at a VAF of >=2%. Mutation persistence was most frequent in DNMT3A (65%
      of patients with mutations at diagnosis), SRSF2 (64%), TET2 (55%), and ASXL1
      (46%), and significantly associated with older age (p < 0.0001) and, in
      multivariate analyses adjusting for age, genetic risk, and allogeneic
      transplantation, with inferior relapse-free survival (hazard ratio (HR), 2.34; p
      = 0.0039) and overall survival (HR, 2.14; p = 0.036). Patients with persisting
      mutations had a higher cumulative incidence of relapse before, but not after
      allogeneic stem cell transplantation. Our work underlines the relevance of
      mutation persistence during first remission as a novel risk factor in AML.
      Persistence of pre-leukemic clones may contribute to the inferior outcome of
      elderly AML patients. Allogeneic transplantation abrogated the increased relapse
      risk associated with persisting pre-leukemic clones, suggesting that mutation
      persistence may guide post-remission treatment.

PMID- 29472725
TI  - An ancient family of lytic polysaccharide monooxygenases with roles in arthropod
      development and biomass digestion.
AB  - Thermobia domestica belongs to an ancient group of insects and has a remarkable
      ability to digest crystalline cellulose without microbial assistance. By
      investigating the digestive proteome of Thermobia, we have identified over 20
      members of an uncharacterized family of lytic polysaccharide monooxygenases
      (LPMOs). We show that this LPMO family spans across several clades of the Tree of
      Life, is of ancient origin, and was recruited by early arthropods with possible
      roles in remodeling endogenous chitin scaffolds during development and
      metamorphosis. Based on our in-depth characterization of Thermobia's LPMOs, we
      propose that diversification of these enzymes toward cellulose digestion might
      have endowed ancestral insects with an effective biochemical apparatus for
      biomass degradation, allowing the early colonization of land during the Paleozoic
      Era. The vital role of LPMOs in modern agricultural pests and disease vectors
      offers new opportunities to help tackle global challenges in food security and
      the control of infectious diseases.

PMID- 29472726
TI  - Combinatory use of distinct single-cell RNA-seq analytical platforms reveals the
      heterogeneous transcriptome response.
AB  - Single-cell RNA-seq is a powerful tool for revealing heterogeneity in cancer
      cells. However, each of the current single-cell RNA-seq platforms has inherent
      advantages and disadvantages. Here, we show that combining the different single
      cell RNA-seq platforms can be an effective approach to obtaining complete
      information about expression differences and a sufficient cellular population to
      understand transcriptional heterogeneity in cancers. We demonstrate that it is
      possible to estimate missing expression information. We further demonstrate that
      even in the cases where precise information for an individual gene cannot be
      inferred, the activity of given transcriptional modules can be analyzed.
      Interestingly, we found that two distinct transcriptional modules, one associated
      with the Aurora kinase gene and the other with the DUSP gene, are aberrantly
      regulated in a minor population of cells and may thus contribute to the possible
      emergence of dormancy or eventual drug resistance within the population.

PMID- 29472727
TI  - Nondestructive in-line sub-picomolar detection of magnetic nanoparticles in
      flowing complex fluids.
AB  - Over the last decades, the use of magnetic nanoparticles in research and
      commercial applications has increased dramatically. However, direct detection of
      trace quantities remains a challenge in terms of equipment cost, operating
      conditions and data acquisition times, especially in flowing conditions within
      complex media. Here we present the in-line, non-destructive detection of magnetic
      nanoparticles using high performance atomic magnetometers at ambient conditions
      in flowing media. We achieve sub-picomolar sensitivities measuring ~30 nm
      ferromagnetic iron and cobalt nanoparticles that are suitable for biomedical and
      industrial applications, under flowing conditions in water and whole blood.
      Additionally, we demonstrate real-time surveillance of the magnetic separation of
      nanoparticles from water and whole blood. Overall our system has the merit of in
      line direct measurement of trace quantities of ferromagnetic nanoparticles with
      so far unreached sensitivities and could be applied in the biomedical field
      (diagnostics and therapeutics) but also in the industrial sector.

PMID- 29472728
TI  - Lessons Learned from Crime Caught on Camera.
AB  - Objectives: The widespread use of camera surveillance in public places offers
      criminologists the opportunity to systematically and unobtrusively observe crime,
      their main subject matter. The purpose of this essay is to inform the reader of
      current developments in research on crimes caught on camera. Methods: We address
      the importance of direct observation of behavior and review criminological
      studies that used observational methods, with and without cameras, including the
      ones published in this issue. We also discuss the uses of camera recordings in
      other social sciences and in biology. Results: We formulate six key insights that
      emerge from the literature and make recommendations for future research.
      Conclusions: Camera recordings of real-life crime are likely to become part of
      the criminological tool kit that will help us better understand the situational
      and interactional elements of crime. Like any source, it has limitations that are
      best addressed by triangulation with other sources.

PMID- 29472730
TI  - Constant and Variable Time Delays of Synchrony of Facial Expressions in Dyadic
      Conversations.

PMID- 29472729
TI  - Behavior of Weak Polyelectrolyte Brushes in Mixed Salt Solutions.
AB  - Hydrophilic and hydrophobic weak polybasic brushes immersed in aqueous solutions
      of mixed salt counterions are considered using a mean-field numerical self
      consistent field approach. On top of the solvent quality of the polymer, the
      counterion-solvent interactions are accounted for by implementing Flory-Huggins
      interaction parameters. We show that ion specificity within the brush can bring
      about large changes in conformation. It is found that the collapse transition of
      hydrophobic, weak polyelectrolyte brushes features an intermediate two-phase
      state wherein a subset of chains are collapsed in a dense layer at the substrate,
      while the remainder of chains are well-solvated and strongly stretched away from
      the it. Besides pH and ionic strength, solvent quality of counterions and the
      composition of ions in the solvent are important control parameters for the
      behavior of polyelectrolyte brushes. Increasingly hydrophobic counterions
      penetrate deeper within the brush and stabilize the collapsed region, while
      hydrophilic counterions do the opposite.

PMID- 29472731
TI  - Investigating the role of alexithymia on the empathic deficits found in
      schizotypy and autism spectrum traits.
AB  - Alexithymia, the inability to identify and describe one's emotional experience,
      is elevated in many clinical populations, and related to poor interpersonal
      functioning. Alexithymia is also associated with empathic deficits in individuals
      with autism spectrum disorders. Accordingly, a better understanding of
      alexithymia could elucidate the nature of social-cognitive deficits
      transdiagnostically. We investigated alexithymia and components of empathy in
      relation to schizotypal and autism spectrum traits in healthy college students.
      Specifically, we examined higher-order components of empathic processing that
      involve perspective taking and other-oriented concern, which are reduced in
      alexithymia. Higher-order empathic processing was inversely correlated with both
      schizotypal and autism spectrum traits. Bootstrapping techniques revealed that
      alexithymia had a significant indirect effect on the relationship between higher
      order empathy and these personality traits; thus, alexithymia contributes
      uniquely to their relationship. These findings suggest alexithymia represents one
      possible mechanism for the development of empathic deficits in these populations.
      These results are consistent with the perspective that awareness of one's own
      emotional state may predicate a successful empathic response to another's. This
      work highlights the importance of a consideration of alexithymia in elucidating
      the nature of empathic deficits in various clinical populations, and points to a
      potential point of social intervention.

PMID- 29472732
TI  - Is the technical performance of young soccer players influenced by hormonal
      status, sexual maturity, anthropometric profile, and physical performance?
AB  - The aim of this study was to examine the influence of hormonal status,
      anthropometric profile, sexual maturity level, and physical performance on the
      technical abilities of 40 young male soccer players during small-sided games
      (SSGs). Anthropometric profiling, saliva sampling, sexual maturity assessment
      (Tanner scale), and physical performance tests (Yo-Yo and vertical jumps) were
      conducted two weeks prior to the SSGs. Salivary testosterone was determined by
      the enzyme-linked immunosorbent assay method. Technical performance was
      determined by the frequency of actions during SSGs. Principal component analyses
      identified four technical actions of importance: total number of passes,
      effectiveness, goal attempts, and total tackles. A multivariate canonical
      correlation analysis was then employed to verify the prediction of a multiple
      dependent variables set (composed of four technical actions) from an independent
      set of variables, composed of testosterone concentration, stage of pubic hair and
      genitalia development, vertical jumps and Yo-Yo performance. A moderate-to-large
      relationship between the technical performance set and the independent set was
      observed. The canonical correlation was 0.75 with a canonical R2 of 0.45. The
      highest structure coefficient in the technical performance set was observed for
      tackles (0.77), while testosterone presented the highest structure coefficient
      (0.75) for the variables of the independent set. The current data suggest that
      the selected independent set of variables might be useful in predicting SSG
      performance in young soccer players. Coaches should be aware that physical
      development plays a key role in technical performance to avoid decision-making
      mistakes during the selection of young players.

PMID- 29472733
TI  - Androgen interacts with exercise through the mTOR pathway to induce skeletal
      muscle hypertrophy.
AB  - This study was designed to investigate the effects of exogenous androgen and
      resistance exercise on skeletal muscle hypertrophy and the role of the mammalian
      target of rapamycin (mTOR) signalling during the process. A total of 24 male
      Sprague-Dawley rats were randomly assigned to sham operation and
      dihydrotestosterone (DHT) implantation groups with subgroups subjected to
      sedentary conditions or resistance exercise (SHAM+SED, SHAM+EX, DHT+SED, and
      DHT+EX). The experimental procedure lasted for 10 days. The mRNA expression of
      androgen receptor (AR) and insulin-like growth factor I (IGF-I), the expression
      of myosin heavy chain (MHC), as well as the phosphorylation statuses of AR, mTOR,
      p70 ribosomal S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E
      binding protein 1 (4EBP1) were determined in the white gastrocnemius muscle. The
      cross sectional area and wet mass of the muscle were also measured. The cross
      sectional area and MHC expression were significantly higher in SHAM+EX, DHT+SED,
      and DHT+EX than in SHAM+SED. There was no significant difference among groups in
      muscle mass. The mRNA expression of AR and IGF-I and the phosphorylation of mTOR,
      p70S6K, and 4EBP1 were significantly increased in DHT+SED and SHAM+EX and were
      significantly enhanced in DHT+EX compared with either DHT or exercise alone.
      These data show that DHT causes hypertrophy in skeletal muscle and that exercise
      has a synergistic effect on DHT-induced hypertrophy. Exercise enhances androgen
      induced rapid anabolic action, which involves activation of the mTOR pathway.

PMID- 29472734
TI  - A meta-analysis of the association of CKM gene rs8111989 polymorphism with sport
      performance.
AB  - The muscle-specific creatine kinase (CKM) A/G variants (rs8111989) have been
      associated with skeletal muscle performance in humans; they are correlated with
      physical performance and contribute to differences in the maximum oxygen uptake
      (VO2max) responses during power or endurance training. However, there is not
      enough definitive evidence to demonstrate whether the A and G allelic variants of
      the CKM gene rs8111989 are indeed genetic factors that can influence human
      physical performance. In our study, we identified 9 articles on CKM in a
      literature search, and conducted two meta-analyses on the CKM rs8111989 A/G
      allele or genotype differences between power or endurance athletes and general
      controls. We found that the power athletes had a significantly higher frequency
      of the G allele (OR, 1.14; 95% CI, 1.02-1.28, P=0.03) and GG genotype (OR, 1.54;
      95% CI, 1.24-1.91, P<0.0001) compared to controls, but there was no significant
      difference for the endurance athletes (G allele, OR, 0.95, 95%CI, 0.85-1.06,
      P=0.34; GG genotype, OR, 1.00, 95%CI, 0.78-1.27, P=1.00). The results provide
      additional evidence to support the notion that human physical performance might
      be influenced by genetic profiles, especially in power sports.

PMID- 29472735
TI  - Expression analysis of selected classes of circulating exosomal miRNAs in soccer
      players as an indicator of adaptation to physical activity.
AB  - Recently studies have shown that, depending on the type of training and its
      duration, the expression levels of selected circulating myomiRNAs (c-miR-27a,b, c
      miR-29a,b,c, c-miR-133a) differ and correlate with the physiological indicators
      of adaptation to physical activity. To analyse the expression of selected classes
      of miRNAs in soccer players during different periods of their training cycle. The
      study involved 22 soccer players aged 17-18 years. The multi-stage 20-m shuttle
      run test was used to estimate VO2 max among the soccer players. Samples serum
      were collected at baseline (time point I), after one week (time point II), and
      after 2 months of training (time point III). The analysis of the relative
      quantification (RQ) level of three exosomal myomiRNAs, c-miRNA-27b, c-miR-29a,
      and c-miR-133, was performed by quantitative polymerase chain reaction (qPCR) at
      three time points - before the training, after 1 week of training and after the
      completion of two months of competition season training. The expression analysis
      showed low expression levels (according to references) of all evaluated myomiRNAs
      before the training cycle. Analysis performed after a week of the training cycle
      and after completion of the entire training cycle showed elevated expression of
      all tested myomiRNAs. Statistical analysis revealed significant differences
      between the first and the second time point in soccer players for c-miR-27b and c
      miR-29a; between the first and the third time point for c-miR-27b and c-miR-29a;
      and between the second and the third time point for c-miR-27b. Statistical
      analysis showed a positive correlation between the levels of c-miR-29a and VO2
      max. Two months of training affected the expression of c-miR-27b and miR-29a in
      soccer players. The increased expression of c-miR-27b and c-miR-29 with training
      could indicate their probable role in the adaptation process that takes place in
      the muscular system. Possibly, the expression of c-miR-29a will be found to be
      involved in cardiorespiratory fitness in future research.

PMID- 29472736
TI  - Variations in leptin, nesfatin-1 and irisin levels induced by aerobic exercise in
      young trained and untrained male subjects.
AB  - The aims of this study were to investigate the impacts of acute aerobic exercise
      on circulating levels of hormones associated with energy metabolism, namely
      leptin, nesfatin-1 and irisin, in trained and untrained male subjects and to
      determine whether the timing of the exercise (i.e. morning or night) amplified
      these impacts. Thirty trained (19.2+/-0.7 years) and 30 untrained (19.5+/-0.6
      years) male subjects performed two aerobic running exercises (3 days between
      tests) to 64-76% of the subjects' maximal heart rate for about 30 min. Pre- and
      post-exercise venous blood samples were taken and analysed for leptin, nesfatin-1
      and irisin using enzyme-linked immunosorbent assay (ELISA). Paired samples and
      independent samples t-tests were used to analyse data. Irisin levels increased in
      all the subjects (p<0.001). In both groups, nesfatin-1 levels increased
      significantly after the night-time exercise (p<0.05). Importantly, leptin and
      nesfatin-1 levels varied among the trained and untrained groups: Both leptin and
      nesfatin-1 levels increased in 4 (13%) and 12 (40%) subjects, respectively, after
      the morning exercises, and they increased in 9 (30%) and 10 (33%) subjects,
      respectively, after the night-time exercise. They decreased in 5 (16%) and 7
      (23%) subjects, respectively, after the morning exercise and in 6 (20%) and 3
      (10%) subjects, respectively, after the night-time exercise. Exercise may result
      in increased energy consumption by altering irisin levels. However, due to
      variations among individuals, increasing leptin and nesfatin-1 levels by reducing
      food intake may not be applicable.

PMID- 29472737
TI  - Associations of serum leptin, ghrelin and peptide YY levels with physical
      activity and cardiorespiratory fitness in adolescent boys with different BMI
      values.
AB  - : The aim of this study was to investigate the differences in associations of
      serum acylated and des-acylated ghrelin, peptide YY (PYY) and leptin levels with
      physical activity (PA) and cardiorespiratory fitness (CReF) in adolescent boys
      (mean age of 14.0 years) with overweight (OWB; n=55) and with normal weight (NWB;
      n=154). METHODS: Total PA was measured by 7-day accelerometry (counts/min) and
      CReF by peak oxygen consumption (VO2peak/kg). RESULTS: No differences were found
      in serum PYY, acylated ghrelin or des-acyl ghrelin levels, whereas mean leptin
      (11.6+/-10.6 vs. 2.0+/-2.7 ng/ml; p<0.05) and insulin (18.1+/-8.7 vs. 11.0+/-6.2
      mU/l; p<0.05) levels were significantly higher in OWB compared to NWB. Mean CReF
      was significantly lower in OWB compared to NWB (39.7+/-8.7 vs. 50.5+/-6.8
      ml/min/kg; p<0.05). Leptin was negatively correlated with CReF in both groups (r=
      0.43; p<0.05), des-acylated ghrelin with CReF only in OWB (r =-0.36; p<0.05). In
      OWB leptin was negatively correlated with total PA (r=-0.32; p<0.05) and
      positively with sedentary time of PA (r=0.35; p<0.05). In NWB 28.1% of the
      variability of CReF was determined by leptin and insulin resistance index (HOMA
      IR), whereas in OWB 71.9% was determined by trunk FM and BMI. CONCLUSIONS: Leptin
      concentration was inversely associated with CReF in adolescent boys independently
      of BMI in both groups, while des-acylated ghrelin was associated with CReF only
      in OWB. Low PA in OWB was associated with high serum leptin level.

PMID- 29472738
TI  - Taurine supplementation improves economy of movement in the cycle test
      independently of the detrimental effects of ethanol.
AB  - Taurine (TA) ingestion has been touted as blunting the deleterious effects of
      ethanol (ET) ingestion on motor performance. This study investigated the effects
      of ingestion of 0.6 mL.kg-1 of ET, 6 grams of TA, and ethanol in combination with
      taurine (ET+TA) on economy of movement (EM) and heart rate (HR). Nine volunteers,
      five female (22 +/- 3 years) and four male (26 +/- 5 years), participated in a
      study that used a counterbalanced experimental design. EM and HR were measured
      for 6 min while the subjects were pedalling at a fixed load 10% below the
      anaerobic threshold. The blood alcohol concentration (BAC) was similar between ET
      and ET+TA treatments at 30 min after ingestion and after exercise (12.3 mmol.L-1
      vs. 13.7 mmol.L-1, and 9.7 mmol * L-1 vs 10.9 mmol.L-1, respectively). EM was
      significantly different among treatments, with lower mL.W-1 following ingestion
      of TA (-7.1%, p<0.001) than placebo and ET+TA (-2.45%, p=0.001) compared to ET.
      HR (bpm) was significantly (p<0.05) higher for ET (137 +/- 14 bpm) than the other
      three treatments (placebo = 129 +/- 14 bpm; TA = 127 +/- 11 bpm; TA+ET = 133 +/-
      12 and ET = 137 +/- 14 bpm). Taurine improved EM when compared to placebo or ET,
      and reduced HR when compared to ET. The combination of ET+TA also enhanced EM
      compared to placebo, and reduced HR in comparison to ET alone. Therefore, these
      findings indicate that taurine improves EM and counteracts ethanol-induced
      increases in HR during submaximal exercise.

PMID- 29472739
TI  - Longitudinal effects of swimming on bone in adolescents: a pQCT and DXA study.
AB  - The aims of the present study were, firstly, to evaluate areal bone mineral
      density (aBMD), bone strength and structure during a swimming season and compare
      them to those of normo-active controls (CG), and secondly to ascertain whether
      practising an additional weight-bearing sport other than swimming might improve
      bone. Twenty-three swimmers who only swam (SWI-PURE; 14 males, 9 females), 11
      swimmers who combined swimming with an additional weight-bearing sport (SWI
      SPORT; 8 males, 3 females) and 28 controls (CG; 16 males, 12 females)
      participated in the present study. aBMD was assessed with dual energy X-ray
      (DXA). Bone mass, area, structure and strength of the non-dominant tibia and
      radius were measured with peripheral quantitative computed tomography (pQCT).
      Measurements were performed at the beginning of the swimming season and 8 months
      later. The only difference among groups for DXA and pQCT variables was found for
      arm aBMD, which was higher in the SWI-SPORT than in the CG group at both pre- and
      post-evaluation. Group by time interactions (GxT) were found for trochanter aBMD
      when comparing SWI-SPORT to CG and SWI-SPORT to SWI-PURE, favouring in both cases
      SWI-SPORT. No GxT were found for the radius. For the tibia, GxT were found
      between SWI-SPORT and CG and between SWI-PURE and CG, in both cases favouring the
      swimmers. A season of swimming does not confer any additional benefits to aBMD,
      but may confer minor benefits to structure and mass. Complementing swimming with
      a weight-bearing activity is beneficial to bone.

PMID- 29472740
TI  - Physiological and performance changes in national and international judo athletes
      during block periodization training.
AB  - Block periodization (BP) has been proposed as an alternative approach for
      application in the context of high-level sports. Despite its growing acceptance,
      there is no empirical evidence of BP adoption in high-level judo athletes.
      Therefore, this study aimed to compare the maximal strength, muscle power, judo
      specific performances, and hormonal concentration changes of state/national level
      (NG) and international level (IG) judo athletes subjected to BP. Twenty-one elite
      judo athletes (international level = 10; 21.7+/-1.9 years, 167.2+/-7.6 cm, 67.6+/
      9.4 kg, 15.7+/-1.9 years of practice; national level = 11; 21.9+/-3.0 years,
      167.5+/-9.1 cm, 71.8+/-16.5, 15.9+/-3.0 years of practice) were subjected to 13
      week BP training (5-week accumulation phase [ACP], 5-week transmutation phase
      [TP], and 3-week realization phase [RP]). The judo-specific performance (SJFT)
      increased as there was observed a decrease in the SJFT index (final heart rate
      [HR] (bpm) + HR1 min after the test divided by the number of throws) for both NG
      (effect size [ES] = 0.83) and IG (ES = 0.53) from ACP to TP (p < 0.05). The row
      exercise maximal strength decreased (p < 0.05; ES = 1.35) after the ACP but
      returned to the baseline level after the TP, for the whole group (ES = 1.39). The
      athletes did seem to cope appropriately with the demands of BP, as besides
      increases in SJFT performance no significant changes were observed for cortisol
      and testosterone concentrations. This is the first study to demonstrate that judo
      athletes from different competitive levels subjected to BP improved SJFT, likely
      due to an appropriate balance between training loads and recovery. Thus, the BP
      approach may be a useful alternative periodization strategy for high-level judo
      athletes.

PMID- 29472741
TI  - Effects of order and sequence of resistance and endurance training on body fat in
      elementary school-aged girls.
AB  - The purpose of this study was to analyse the effects of order and sequence of
      concurrent resistance and endurance training on body fat percentage (BFP) in a
      large sample of elementary school-aged girls. One hundred and twenty-six healthy
      girls, aged 10-11 years (10.95 +/- 0.48 years), were randomly assigned to six
      groups to perform different training protocols per week for 8 weeks: Resistance
      only (R), Endurance-only (E), Concurrent Distinct Endurance-Resistance (CDER),
      Concurrent Parallel Endurance-Resistance (CPER), Concurrent Parallel Resistance
      Endurance (CPRE), and a Control group (C). In R and E, the subjects performed
      single sessions of resistance or endurance exercises, respectively (two days per
      week). In CDER, resistance-endurance training was performed on different days
      each week (four days per week). CPER and CPRE performed single-session combined
      endurance-resistance training or combined resistance-endurance training,
      respectively, each week (two days per week). After an 8-week training period, BFP
      decreased in all experimental groups (CPER: 13.3%, p< 0.05; CPRE: 13.8%, p<0.001;
      E: 1.9%, p>0.05; R: 5.0%, p>0.05; and CDER: 5.6%, p>0.05). However, a significant
      difference was found in CPER and CPRE when compared to CDER, E, and R, indicating
      that training sequence may influence BFP. All programmes were effective, but CPER
      and CPRE obtained better results for BFP than CDER, E, or R. The effects of
      concurrent resistance and endurance training on body fat percentage can be
      mediated by order and sequence of exercise. These results provide insight into
      optimization of school-based fat loss exercise programmes in childhood.

PMID- 29472742
TI  - Effects of high-intensity interval training on body composition, aerobic and
      anaerobic performance and plasma lipids in overweight/obese and normal-weight
      young men.
AB  - To examine the effects of short high-intensity interval training (HIIT) on body
      composition, physical performance and plasma lipids in overweight/obese compared
      to normal-weight young men. Nine overweight/obese and nine normal-weight men
      (control group) aged 17 to 20 years underwent a HIIT programme three times per
      week for eight weeks. Body composition, indices of aerobic [maximal aerobic
      velocity (MAV) and maximal oxygen uptake (VO2max)] and anaerobic [squat jump
      (SJ), counter-movement jump (CMJ), five-jump test (FJT), 10-m and 30-m sprint]
      performances, as well as fasting plasma lipids, were assessed in the two groups
      at PRE and POST HIIT. The HIIT programme resulted in significant reductions in
      body mass (-1.62%, P=0.016, ES=0.11) and fat mass (-1.59%, P=0.021, ES=0.23) in
      obese, but not in normal-weight subjects. MAV (+5.55%, P=0.005, ES=0.60 and
      +2.96%, P=0.009, ES=0.82), VO2max (+5.27%, P=0.006, ES=0.63 and +2.88%, P=0.009,
      ES=0.41), FJT (+3.63%, P=0.005, ES=0.28 and +2.94%, P=0.009, ES=0.52), SJ
      (+4.92%, P=0.009, ES=0.25 and +6.94%, P=0.009, ES=0.70) and CMJ (+6.84%, P=0.014,
      ES=0.30 and +6.69%, P=0.002, ES=0.64) significantly increased in overweight/obese
      and normal-weight groups, respectively. 30-m sprint time significantly decreased
      in both groups (-1.77%, P=0.038, ES=0.12 and -0.72%, P=0.030, ES=0.16). Plasma
      total cholesterol (-11.8%, P=0.026, ES=0.96), LDL cholesterol (-11.9%, P=0.050,
      ES=0.77) and triglycerides (-21.3%, P=0.023, ES=1.08) significantly decreased in
      the obese group, but not in the normal-weight group. The eight-week HIIT
      programme resulted in a slight improvement in physical fitness and a significant
      decrease in plasma lipids in the obese. Short duration HIIT may contribute to an
      improved cardiometabolic profile in the obese.

PMID- 29472743
TI  - Performance analysis of male handball goalkeepers at the World Handball
      championship 2015.
AB  - Goalkeepers have a very important role in handball. In coaching communities it is
      well recognized that goalkeepers' performances can predict team ranking in major
      tournaments. Despite this, few studies have been conducted on elite goalkeepers
      participating in World Championships. Therefore, the purpose of this study was to
      analyse goalkeepers' save performance during the 88 matches of the 2015 men's
      World Championships tournament. Goalkeepers from 24 national teams were analysed
      using a tracking camera system and bespoke software (Prozone Handball V.1.2,
      Prozone, Leeds, UK). The purpose of this study was to examine time-motion
      performance parameters and to evaluate the save rates for each goalkeeper. The
      mean total distance covered in a game by the goalkeepers was 1634+/-999 m.
      Goalkeepers spent most of the time walking or standing. The total amount of shots
      to the goal was 6893, with a mean save percentage of 30% (2088 saves). A
      significant relationship was identified between the goalkeepers' save statistics
      and the final team rankings. The save rate is important for teams to achieve a
      higher ranking, and therefore the selection and training of goalkeepers requires
      more than just assessing physical abilities. The throwing distribution and
      success/save rate during the Qatar 2015 Men Handball World Championships suggest
      strong and weak parts of the goal area, and coaches can use this information to
      adjust their training approaches for both goalkeepers and shooters.

PMID- 29472744
TI  - Properties of body composition of female representatives of the Polish national
      fencing team - the sabre event.
AB  - Fencing is a combat sport whose form of direct confrontation involves hitting the
      opponent with a weapon. The purpose of the study was to determine the properties
      of body composition of female representatives of the Polish national fencing
      team. The study involved 11 female athletes of the Polish national fencing team.
      Their age was 16-22 years (19+/-2.32), body weight 52-78 kg (59.7+/-7.4), body
      height 158-183 cm (167.46+/-6.10) and the training experience 7.64+/-3.47 years.
      The reference group consisted of 153 students of Warsaw University of Technology
      (Poland). Twenty basic somatic characteristics were measured. The following
      indices were calculated: slenderness, Rohrer's, BMI, Manouvrier's, and pelvic
      shoulder indices. Density of the body, total body fat, active tissue, the overall
      profile of body composition and internal proportions of the body were determined.
      Analysis of internal proportions of factors of the athletes' body composition
      revealed significant differences in particular groups of features. The total size
      of the athletes' bodies is due to less-than-average magnitude of the length and
      stoutness characteristics and a high magnitude of adiposity (M = 0.63) in the
      Polish female national team of fencers (sabre) calculated from the normalized
      values for the control group. The proportions of features within the analysed
      factors revealed a significant advantage of the length of the upper extremity
      over the lower one and a distinct advantage of forearm musculature. The specific
      profile of body composition of female athletes practising sabre fencing is most
      likely due to long-term effects of training as well as the system of selection of
      persons with specific somatic prerequisites developed in the course of many years
      of training practice.

PMID- 29472745
TI  - Effects of seawater ingestion on lactate response to exercise in runners.
AB  - The aim of this study was to examine the effect of microfiltered and sterilized
      seawater ingestion on running performance in a hot environment. This cross-over,
      double-blind randomized trial included 12 experienced male runners. The subjects
      randomly consumed seawater (SW) or pure water (placebo) in an equivalent amount
      of 50 ml five minutes prior to running at 40% of their VO2 max for 95.0 +/- 18.5
      min, at 30 degrees C, until they lost 3% of body weight. Every 20 minutes, a
      measurement of their body weight was taken and a blood lactate analysis was
      performed. The concentration of lactate was significantly lower after the running
      exercise in the SW condition compared to placebo. The results of this study
      provide evidence supporting the ergogenic effects of microfiltered and sterilized
      seawater ingestion on running performance and lactate production.

PMID- 29472746
TI  - Being an 'adolescent': The consequences of gendered risks for young people in
      rural Uganda.
AB  - The behaviour of adolescents is recognised increasingly as having substantial and
      long-term consequences for their health. We examined the meaning of 'adolescence'
      in southern Uganda with HIV-positive young people aged 11-24 years. Adolescent
      girls and boys are described differently in the local language (Luganda).
      Adolescence is described as a behavioural rather than a life course category and
      an inherently dangerous one. The practices, risks and consequences of
      'adolescent' behaviour are highly gendered. Local understandings of adolescence
      are likely to have a significant impact on the efficacy of interventions designed
      to minimise their 'risky behaviour'.

PMID- 29472748
TI  - Efficacy and Safety of Oral Diclofenac Sustained release Versus Transdermal
      Diclofenac Patch in Chronic Musculoskeletal Pain: A Randomized, Open Label Trial.
AB  - Introduction: To compare the efficacy, safety, and tolerability of transdermal
      patches of diclofenac sodium with oral diclofenac sustained release (SR) in
      patients of chronic musculoskeletal MSK pain conditions. Materials and Methods:
      The eligible patients were given either transdermal diclofenac patch or tablet
      diclofenac SR. Pain was assessed at 2 and 4 weeks using a visual analog scale.
      Adverse events were recorded. Patients with 18-65 years old of either gender with
      score of >=4 on a 11-item numeric rating scale-numeric version of visual analog
      scale for pain with diagnosis of primary osteoarthritis (OA) of the knee or hand
      of at least 3 months duration, with independent radiological confirmation of OA
      or having pain associated with other MSK conditions such as soft-tissue
      rheumatism, cervical and lumbar back pain, and fibromyalgia, of at least 3 months
      duration were included in this study. Results: Transdermal diclofenac
      diethylamine patch and tablet diclofenac sodium sustained release (SR) do not
      significantly differ in the reduction of numerical rating scores at the end of 4
      weeks (P = 0.8393). Conclusion: Transdermal diclofenac was equi-efficacious as
      tablet diclofenac sodium SR in reducing pain due to chronic MSK pain conditions.

PMID- 29472749
TI  - Learning Pharmacology by Metaphors: A Tale of Beta-blockers.

PMID- 29472747
TI  - Lercanidipine in the Management of Hypertension: An Update.
AB  - Calcium channel blockers (CCBs), particularly dihydropyridine-CCBs, (DHP-CCBs),
      have an established role in antihypertensive therapy, either as monotherapy or in
      combination with other antihypertensive drugs. Two hundred and fifty-one papers
      published in PubMed in English between January 1, 1990, and October 31, 2016,
      were identified using the keyword "lercanidipine." Lercanidipine is a lipophilic
      third-generation DHP-CCB, characterized by high vascular selectivity and
      persistence in the smooth muscle cell membranes. Lercanidipine is devoid of
      sympathetic activation, and unlike the first and second generation of DHP-CCBs,
      it dilates both the afferent and the efferent glomerular arteries, while
      preserving the intraglomerular pressure. In addition, lercanidipine prevents
      renal damage induced by angiotensin II and demonstrates anti-inflammatory,
      antioxidant, and anti-atherogenic properties through an increasing
      bioavailability of endothelial nitric oxide. It is associated with a regression
      of microvascular structural modifications in hypertensive patients. The efficacy
      of lercanidipine has been demonstrated in patients with different degrees of
      hypertension, in the young and elderly and in patients with isolated systolic
      hypertension. In patients with diabetes and renal impairment, lercanidipine
      displays a renal protection with a significant decrease of microalbuminuria and
      improvement of creatinine clearance. Lercanidipine is well tolerated and is
      associated with a very low rate of adverse events, particularly ankle edema,
      compared with amlodipine and nifedipine. In conclusion, lercanidipine produces a
      sustained blood pressure-lowering activity with a high rate of
      responder/normalized patients, associated with a favorable tolerability profile.

PMID- 29472750
TI  - Vitamin B12 Supplementation and Methylcobalamin: Use or Misuse.

PMID- 29472751
TI  - Levosulpiride-induced Movement Disorders.
AB  - We reported a series of patients who presented with LSP-induced movement
      disorders specifically, dyskinetic movements. We have presented one case of LSP
      induced parkinsonism and summarized ten cases of LSP-induced dyskinesia. The
      causality of the adverse drug reaction was assessed systematically using a
      validated rating system, and we extensively qualified the clinical presentation
      of each case of dyskinesia using a clinical rating scale. We described an unusual
      case of acute onset LSP-induced parkinsonism in a 56-year-aged female. The mean
      age of ten patients of LSP-induced dyskinesia was 65.3 years (standard deviation
      10.4), and 25% of patients were female. They were consuming suspected medication
      for a median duration of 13 months (range 1-60 months). We noted LSP-induced
      dyskinesia was challenging to treat as its resolution is often incomplete even
      with adequate treatment.

PMID- 29472752
TI  - Low-Dose Mirtazapine-Induced Nightmares Necessitating its Discontinuation in a
      Young Adult Female.
AB  - Mirtazapine is a novel tetracyclic antidepressant which enhances noradrenergic
      and serotonergic transmission by blocking central alpha2-adrenergic auto- and
      hetero-receptors. Due to favorable safety and adverse effect profile, it is often
      viewed as a promising agent for treatment of depression. Particularly, its
      anxiolytic and sleep-improving properties have led to its favorable positioning
      for the management of depression with insomnia. Our objective is to describe a
      case of depression with treatment-emergent nightmares induced by mirtazapine. A
      21-year-old female medical student was diagnosed with moderate depression with
      prominent insomnia and initiated on tablet mirtazapine 7.5 mg subsequent to a
      failed trial of selective serotonin reuptake inhibitor. On each of the next 7
      days, she developed nightmares that were quite distressing and terrifying. As per
      the patient's request, tablets were stopped. The side effect abated within 2 days
      of stopping the agent, and this close temporal relationship suggests a causal
      role for mirtazapine in inducing the adverse reaction. Nightmares are usually
      associated with rapid eye movement (REM) sleep, and literature is inconsistent
      about the effect of mirtazapine on REM sleep parameters. Nevertheless, clinicians
      need to be forewarned about the possibility of developing treatment-limiting REM
      sleep phenomena such as nightmares when using antidepressants without prominent
      REM suppressant properties such as mirtazapine. The putative mechanisms behind
      these rare adverse reactions are discussed.

PMID- 29472753
TI  - Autopsy-proven Mirtazapine Withdrawal-induced Mania/Hypomania Associated with
      Sudden Death.
AB  - Manic episodes induced by antidepressant withdrawal are rarely reported.
      Mirtazapine is a tetracyclic, piperazinoazepine compound and is a noradrenergic,
      adrenergic, serotonergic, histaminergic, and muscarinic-antagonist antidepressant
      that is used for the treatment of major depression and other psychiatric
      illnesses. There are several reported cases of manic/hypomanic episodes induced
      by mirtazapine withdrawal based on suspected clinical symptoms that were not
      confirmed by autopsy and toxicology. We present the first reported case of
      mirtazapine withdrawal-induced mania/hypomania associated with sudden death and
      confirmed by autopsy and toxicology. Our patient was a 26-year-old male who had
      been diagnosed with schizophreniform disorder, borderline intellectual
      functioning, polysubstance abuse, mild mental retardation, and attention deficit
      hyperactive disorder. He took only mirtazapine in the final and terminal weeks of
      his life and stopped taking mirtazapine 4 days before his death. He exhibited a
      sudden manic/hypomanic episode and died during a physical altercation during this
      episode. A full autopsy with comprehensive toxicologic analysis of his body
      fluids and tissues was performed. Autopsy revealed that he died from blunt force
      trauma of the head, neck, and trunk with extremely low and markedly
      subtherapeutic levels of mirtazapine and desmethylmirtazapine in the blood
      (mirtazapine: 0.005 mg/L; desmethylmirtazapine 0.011 mg/L). Advanced selective
      radioligand and neurochemical assays for density and affinity-binding parameters
      of dopamine transporter and heat shock protein 70 did not reveal any evidence of
      excited delirium or autonomic hyperactivity state. We recommend that toxicologic
      analysis of blood for antidepressants should become routine parts of autopsy
      protocols for the investigation of sudden death following terminal
      manic/hypomanic episodes for further elucidation of mania/hypomania induced by
      antidepressant withdrawal.

PMID- 29472754
TI  - Prevalence of Obesity After Spinal Cord Injury.
AB  - The prevalence of obesity has been continuously increasing in the United States.
      Obesity has crossed the borders of the able-bodied populations and extended to
      populations with disabilities, including spinal cord injury (SCI). The magnitude
      and the prevalence of obesity after SCI are not clearly defined. The purpose of
      the current review is to discuss the body of literature on the prevalence of
      obesity among individuals with SCI. The review will show that the prevalence of
      obesity after SCI is an issue that needs to be further addressed and specifically
      correlated to mortality rates in SCI. Body mass index (BMI) criteria need to be
      adjusted to meet the changes in body composition after SCI, specifically
      increasing fat mass and percent body fat. Prevalence of overweight and obesity in
      SCI by sex, age, and ethnic group needs further investigation to determine the
      actual magnitude of the problem, which appears to exceed epidemic proportions.
      Moreover, SCI-specific factors such as level of injury, American Spinal Injury
      Association (ASIA) impairment classification, and time since injury need to be
      further correlated to the prevalence of obesity after SCI.

PMID- 29472755
TI  - Investigation of the Stereoselective Synthesis of the Indane Dimer PH46A, a New
      Potential Anti-inflammatory Agent.
AB  - PH46A, belonging to a class of 1,2-Indane dimers, has been developed by our
      research group as a potential therapeutic agent for the treatment of inflammatory
      and autoimmune diseases. The initial synthetic route to PH46A gave a low overall
      yield, due in large part to the generation of undesired diastereoisomer 5 and the
      unwanted enantiomer (R,R)-8 during the synthesis. The aim of this work was to
      carry out a comprehensive investigation into the stereoselective synthesis of
      PH46A. Significant progress was made on the ketone reduction step, where the use
      of triisobutylaluminum [TiBA, Al(iBu)3] afforded high selectivity for the target
      diastereoisomer (rac)-6, compared to the unfavorable ratio obtained using a
      previous process. This enabled a multikilo scale synthesis of PH46A in a GMP
      environment. Further, a brief proof-of-principle investigation was carried out
      using an achiral phase transfer catalyst (PTC) for alkylation at the methine
      carbon of the parent indanone.

PMID- 29472756
TI  - Robotic TAPP Ventral Hernia Repair: Early Lessons Learned at an Inner City Safety
      Net Hospital.
AB  - Background and Objectives: Ventral hernia repair is one of the most commonly
      performed general surgery procedures, and minimally invasive approaches are
      increasingly preferred. The physiologic repair offered by the preperitoneal
      approach is favorable, with reduced complications, but it remains a technical
      challenge. The robotic platform allows for enhanced instrument flexibility and
      ease of operation. We conducted a retrospective review of our experience with
      robotic transabdominal preperitoneal repair (rTAPP) versus robotic
      intraperitoneal onlay mesh (rIPOM) at a tertiary care hospital in an urban
      setting. Methods: We reviewed the records of patients undergoing minimally
      invasive ventral hernia repair from March 2014 through March 2017. Demographics,
      complication rates, and operative time were compared by t test and Chi square
      test, as applicable. Results: Sixty-three patients met the criteria for inclusion
      in the study. Of those, 27 underwent ventral hernia repair with rIPOM and 36 with
      rTAPP, with no major intraoperative complications. There were no significant
      differences in demographics between the 2 groups in age, BMI, and sex. The
      difference in mean operative time was not significant (rIPOM 167.26 [SD 51.76]
      minutes vs rTAPP 158.84 minutes [SD 61.5]; P = .57), whereas mean console time
      was significantly different (rIPOM 70.88 minutes [SD 32.88] vs rTAPP 90.26 [SD
      31.17]; P = .018). Postoperative complications occurred only with rIPOM and
      included urinary retention, seroma, and fever. Conclusions: rTAPP is a promising
      alternative to rIPOM, with reduced complications without adding significant
      operative time, and may allow for reduced costs.

PMID- 29472757
TI  - Trifecta Outcomes to Assess Learning Curve of Robotic Partial Nephrectomy.
AB  - Background and Objectives: The learning curve for achieving desirable
      perioperative outcomes in robot-assisted partial nephrectomy (RAPN) has not been
      well studied. Information is available regarding "trifecta" outcomes of no
      complications, no positive margins, warm ischemia time (WIT) of <=25 minutes, and
      a <=15% decrease in postoperative glomerular filtration rate (GFR). This study
      was conducted to assess the impact of the learning curve on surgical outcomes in
      patients undergoing RAPN. Methods: We reviewed 131 consecutive patients who
      underwent RAPN by a single, fellowship-trained surgeon from October 2007 through
      June 2015. Patients were divided into 4 subgroups, and mean perioperative values
      were compared. The learning curve was evaluated as the time it took the surgeon
      to attain a trifecta outcome. Results: Means for the RENAL Nephrometry Score,
      procedure length, WIT, and estimated blood loss (EBL) were 5.3 +/- 1.2, 172.1 +/-
      43.5 minutes, 22.7 +/- 7.0 minutes, and 267.2 +/- 341.8 mL, respectively.
      Significance was noted for differences in WIT (P = .50), postoperative creatinine
      (P = .006), postoperative estimated (e)GFR (P = .40), and percentage change in
      creatinine (P = .023). The learning curve for achieving positive outcomes was
      noted in >61-90 cases after 66-80 months of performing minimally invasive partial
      nephrectomy surgeries at a rate of 20 cases per year. Conclusion: RAPN is a safe,
      feasible procedure with slightly better surgical outcomes than laparoscopic
      partial nephrectomy (LPN). In the hands of an experienced surgeon, the learning
      curve for achieving trifecta outcomes can involve a significant number of cases
      over several years.

PMID- 29472758
TI  - Predictors of Reoperation and Failure to Rescue in Bariatric Surgery.
AB  - Background and Objectives: Morbidity and mortality have been shown to increase
      several-fold in patients who have undergone bariatric surgery and returned to the
      operating room after their initial procedures. Failure-to-rescue (FTR) analyses
      allow for an understanding of patient management and outcomes that is more
      distinguished than assessments of adverse occurrences and mortality rates alone.
      The objective of this study was to assess failure to rescue (FTR) and the
      characteristics and outcomes of patients undergoing reoperation after
      laparoscopic gastric bypass (LGBP) and laparoscopic sleeve gastrectomy (LSG).
      Methods: The American College of Surgeons-National Surgical Quality Improvement
      Program (ACS-NSQIP) participant data files were accessed to identify patients >18
      years of age who underwent LGBP and LSG from 2011 through 2015. Patients were
      further classified into 3-day reoperation and nonreoperation cohorts. Patient
      demographics, comorbidities, and baseline health characteristics were collected.
      Pertinent outcomes, complications, and FTR were analyzed. Results: A total of
      96,538 patients were included. Of those, 1,850 (1.92%) returned to the operating
      room, and 94,688 (98.08%) did not. Patients who underwent reoperation had a
      greater likelihood of having any complication (72.20% vs. 51.29%; P < .0001) and
      had a higher overall mortality rate (1.46% vs. 0.10%, P < .0001). The FTR rates
      were 2.01% in the reoperation group and 0.14% in the nonreoperation group (P <
      .0001). Conclusion: Patients who undergo LGBP and LSG and have reoperations are
      at higher risk of developing complications with subsequent mortality.

PMID- 29472759
TI  - TEP With Long-Term Resorbable Mesh in Patients With Indirect Inguinal Hernia.
AB  - Background and Objectives: The role of long-term degradable implants in reducing
      the risk of chronic postoperative pain after inguinal hernia repair is still
      unclear. A pilot study using a synthetic long-term resorbable mesh in
      Lichtenstein repair showed good results regarding pain and discomfort in patients
      with indirect inguinal hernia (IH) without recurrences, but higher recurrence
      rate in patients with direct inguinal hernia (DH). The purpose of this study was
      to assess the incidence of pain and early recurrence in patients with LIH
      surgically treated with the TEP technique using a long-term degradable mesh. This
      is the first human study to use long-term degradable mesh with the TEP approach.
      Methods: This study was prospective, including 35 primary IHs surgically treated
      with TEP repair using TIGR Mesh (Novus Scientific Pte, Ltd, Singapore). At the 1
      year follow-up recurrence was assessed by clinical examination and the incidence
      of pain or discomfort was assessed before and after surgery by Visual Analog
      Scale (VAS) and Inguinal Pain Questionnaire (IPQ). Results: After 12 months, no
      patients had chronic pain. Only 1 (2.8%) patient reported pain using the VAS
      (score = 2), and 4 patients reported pain that could easily be ignored. All 4
      patients reported less pain 1 year after the operation using both IPQ and VAS,
      compared with the preoperative assessment. One patient (2.8%) developed a
      recurrence 20 months after the primary operation. Conclusion: TEP repair using a
      synthetic long-term resorbable mesh was found to be safe and promising regarding
      pain and discomfort at 1-year follow-up in patients with IH. Longer follow-up is
      necessary to establish the risk of recurrence.

PMID- 29472760
TI  - Genetic Diversity and Functional Analysis of Sigma Factors in Enterobacter
      cloacae Complex Resourced From Various Niche.
AB  - Sigma factors are bacterial transcription factors that bind the core RNA
      polymerase and direct transcription initiation at a specific promoter site. These
      specialized sigma factors bind the promoters of genes appropriate to the
      environmental conditions and selectively increase the transcription of those
      genes. Here, we attempt to identify sigma factors in 5 genomes belonging to the
      Enterobacter cloacae complex (Ecc), a group of gram-negative bacteria that are
      important nosocomial pathogens. This process includes the identification of
      orthologous sequences, conserved motifs, domains, families, phylogenetic
      profiles, and protein-protein associations of these components. Based on the
      reference genome, genome-wide comparison revealed that the genomes of
      Enterobacter asburiae JCM6051, Enterobacter nimipressuralis CIP 104980,
      Enterobacter hormaechei ATCC49162, Enterobacter kobei JCM 8580, and Enterobacter
      ludwigii EN-119 encode 10 sigma factors that exist in the reference strain
      Enterobacter cloacae subsp cloacae ATCC13047. Moreover, the sequence similarity,
      protein domains and families of the sigma factors, protein-protein association,
      and phylogenetic profile indicate that the sigma factor proteins of these 5
      strains may have evolutionary relatedness and functional characteristics
      important to their various environmental niches. Interestingly, the absence of
      RpoS in E kobei, which contributes to bacterial survival under environmental
      stress conditions, indicates that RpoS might have been independently acquired and
      may play different roles relating to pathogenicity, host range determination,
      and/or niche adaptation. Future work such as RNA sequencing will be directed
      towards investigating the roles that these sigma factors play in the biology of
      the Ecc.

PMID- 29472761
TI  - More new deep-reef basslets (Teleostei, Grammatidae, Lipogramma), with updates on
      the eco-evolutionary relationships within the genus.
AB  - Two new Lipogramma basslets are described, L. barrettorum and L. schrieri,
      captured during submersible diving to 300 m depth off Curacao, southern
      Caribbean. Superficially resembling L. robinsi in having 11-12 bars of pigment on
      the trunk, L. barrettorum is distinct from L. robinsi in having a stripe of blue
      white pigment along the dorsal midline of the head (vs. a cap of yellow pigment),
      in patterns of pigment on the median fins, and in having 8-10 gill rakers on the
      lower limb of the first arch (vs. 11-12). Lipogramma schrieri is distinct from
      all congeners in having seven or eight dark bars of pigment on the trunk and
      broad, irregular, whitish blue markings on the dorsal portion of the head. The
      new species are genetically distinct from one another and from seven other
      Lipogramma species for which genetic data are available. A phylogenetic
      hypothesis derived from mitochondrial and nuclear genes suggests that the new
      species belong to a clade that also comprises L. evides and L. haberi.
      Collectively those four species are the deepest-living members of the genus,
      occurring at depths predominantly below 140 m. This study thus provides further
      evidence of eco-evolutionary correlations between depth and phylogeny in
      Caribbean reef fishes. Tropical deep reefs are globally underexplored ecosystems,
      and further investigation of Caribbean deep reefs undoubtedly will provide
      samples of species for which no genetic material currently exists and reveal more
      cryptic species diversity in the genus.

PMID- 29472763
TI  - Rhachotropis (Eusiroidea, Amphipoda) from the North East Atlantic.
AB  - The genus Rhachotropis has the widest geographic and bathymetric distribution of
      all amphipod genera worldwide. Molecular and morphological investigations of
      specimens sampled around Iceland and off the Norwegian coast allow the first
      insights into the relationships of North East Atlantic Rhachotropis. The 31
      cytochrome oxidase subunit I (COI) sequences generated for this study were
      assigned 13 Barcode Index Numbers (BINs) in the Barcode of Life database (BOLD),
      of which 12 are new to the database. Molecular analyses of COI and 16S sequences
      could not confirm a theory that depth has a greater influence on the phylogeny of
      Rhachotropis than geographic distance. Although the North East Atlantic is a well
      studied area, our molecular investigations revealed the genus Rhachotropis may
      contain cryptic species, which indicates a higher biodiversity than currently
      known. For example, the specimens which key to Rhachotropis helleri is a complex
      of three COI clades, two of which cannot be identified with morphological traits.
      One specimen of each of the clades in the cladogram was documented by high
      definition photographs. A special focus was on the visual morphology of the eyes,
      as this character shows interspecific differences within the genus Rhachotropis
      in response to fixation in ethanol. Detailed morphological investigation showed
      that some clades thought to be indistinguishable can be separated by minute but
      consistent morphological characters. Datamining Genbank to examine all registered
      COI-sequences of R. aculeata, the only previously known Rhachotropis BIN in the
      North Atlantic and sub-Arctic, showed R. aculeata to be subdivided by an Arctic
      and a North Atlantic population.

PMID- 29472762
TI  - A genetic fingerprint of Amphipoda from Icelandic waters - the baseline for
      further biodiversity and biogeography studies.
AB  - Amphipods constitute an abundant part of Icelandic deep-sea zoobenthos yet
      knowledge of the diversity of this fauna, particularly at the molecular level, is
      scarce. The present work aims to use molecular methods to investigate genetic
      variation of the Amphipoda sampled during two IceAGE collecting expeditions. The
      mitochondrial cytochrome oxidase subunit 1 (COI) of 167 individuals originally
      assigned to 75 morphospecies was analysed. These targeted morhospecies were
      readily identifiable by experts using light microscopy and representative of
      families where there is current ongoing taxonomic research. The study resulted in
      81 Barcode Identity Numbers (BINs) (of which >90% were published for the first
      time), while Automatic Barcode Gap Discovery revealed the existence of 78 to 83
      Molecular Operational Taxonomic Units (MOTUs). Six nominal species (Rhachotropis
      helleri, Arrhis phyllonyx, Deflexilodes tenuirostratus, Paroediceros propinquus,
      Metopa boeckii, Astyra abyssi) appeared to have a molecular variation higher than
      the 0.03 threshold of both p-distance and K2P usually used for amphipod species
      delineation. Conversely, two Oedicerotidae regarded as separate morphospecies
      clustered together with divergences in the order of intraspecific variation. The
      incongruence between the BINs associated with presently identified species and
      the publicly available data of the same taxa was observed in case of Paramphithoe
      hystrix and Amphilochus manudens. The findings from this research project
      highlight the necessity of supporting molecular studies with thorough morphology
      species analyses.

PMID- 29472764
TI  - An alternative approach for evaluating the phenotypic virulence factors of
      pathogenic Escherichia coli.
AB  - Escherichia coli is a recognized zoonotic food-borne pathogen; however, the use
      of polymerase chain reaction (PCR) in the underdeveloped countries to
      differentiate pathogenic from non-pathogenic E. coli is a problematic issue. Our
      grail was to assess the phenotypic virulence markers motility, hemolysin, congo
      red agar, embryo lethality assay and serum resistance for pathogenic E. coli
      (PEC) correlated to PCR tests which is currently used world-wide to evaluate the
      PEC. The 448 strains of Escherichia coli that were isolated from different
      sources, were characterized for phenotypic virulence factors such as motility,
      hemolysin, Congo red binding, Embryo Lethality assay (ELA) and serum resistance,
      as well as antibiotic susceptibility using disc diffusion method to 23
      antibiotics. Results exhibited 100% motility and Congo red binding, 97.1% for
      hemolysin production and 90.2% in the ELA. As a result, we were able to
      hypothetically conclude that the aforementioned virulence markers are plain,
      straightforward, economical, rapid, more dynamic, uncomplicated methodology,
      duplicatable and cost next to nothing when compared to the molecular PCR. Their
      implementation in a diagnostic microbiology laboratory for vetting is a rewarding
      task in the underdeveloped countries. It augments endeavors to minimize the use
      of PCR in our investigations especially during epidemiological and outbreak
      investigations of PEC.

PMID- 29472765
TI  - Effect of dietary fish meal replacement by red algae, Gracilaria arcuata, on
      growth performance and body composition of Nile tilapia Oreochromis niloticus.
AB  - A 12-week long feeding experiment was initiated to evaluate the effect of dietary
      supplementation of red algae, Gracilaria arcuata, on the growth performance, feed
      utilization and body composition of Nile tilapia Oreochromis niloticus (Linnaeus,
      1758). The fish were fed with an algae-free control diet (C) and three
      experimental diets which replaced conventional fish meal with varying levels of
      dried G. arcuata (20%, 40% and 60%, represented as G20, G40 and G60,
      respectively). The growth parameters of final weight (FW), weight gain (WG),
      percentage of weight gain (WG%), daily growth rate (DGR) and specific growth rate
      (SGR) were significantly reduced (P < 0.05) at all levels of algae incorporation
      compared to the control diet. Moreover, the negative impact of Gracilaria meal on
      the growth performance of Nile tilapia increased as the proportion of algae in
      the diet increased, with fish on diet G20 exhibiting a significantly higher
      growth performance than the fish on either of the G40 and G60 diets. On the other
      hand, the feed utilization parameters feed conversion ratio (FCR) and protein
      efficiency ratio (PER) did not show significant differences between the fish in
      the control group and those on diet G20, although poorer FCR and PER outcomes
      were achieved in the case of fish on diet G60. The content of moisture, protein
      and ash in muscle and carcass increased as the proportion of Gracilaria meal in
      the diets increased, but the reverse was true for lipid level. These results
      indicate that incorporation of less than 20% red algae, Gracilaria arcuata, could
      be feasible in the diet of Nile tilapia and further studies are recommended to
      optimize the level of algae to improve growth performance.

PMID- 29472766
TI  - Aquatic ecosystem health and trophic status classification of the Bitter Lakes
      along the main connecting link between the Red Sea and the Mediterranean.
AB  - The Bitter Lakes are the most significant water bodies of the Suez Canal,
      comprising 85% of the water volume, but spreading over only 24% of the length of
      the canal. The present study aims at investigation of the trophic status of the
      Bitter Lakes employing various trophic state indices, biotic and abiotic
      parameters, thus reporting the health of the Lake ecosystem according to the
      internationally accepted classification criteria's. The composition and abundance
      of phytoplankton with a dominance of diatoms and a decreased population density
      of 4315-7376 ind. l-1 reflect the oligotrophic nature of this water body. The
      intense growth of diatoms in the Bitter Lakes depends on silicate availability,
      in addition to nitrate and phosphate. If the trophic state index (TSI) is applied
      to the lakes under study it records that the Bitter Lakes have an index under 40.
      Moreover, in the total chlorophyll-a measurements of 0.35-0.96 ug l-1 there are
      more indicative of little algal biomass and lower biological productivity. At
      0.76-2.3 ug l-1, meanwhile, the low quantity of Phosphorus is a further measure
      of low biological productivity. In the Bitter Lakes, TN/TP ratios are high and
      recorded 147.4, and 184.7 for minimum and maximum ratios, respectively. These
      values indicate that in Bitter lakes, the limiting nutrient is phosphorus and
      confirm the oligotrophic status of the Bitter Lakes. The latter conclusion is
      supported by Secchi disc water clarity measurements, showing that light can
      penetrate, and thus algae can photosynthesize, as deep as >13 m. This study,
      therefore, showed that the Bitter Lakes of the Suez Canal exhibit oligotrophic
      conditions with clear water, low productivity and with no algal blooming.

PMID- 29472767
TI  - Anti-hypertensive and cardioprotective effects of a novel apitherapy formulation
      via upregulation of peroxisome proliferator-activated receptor-alpha and -gamma
      in spontaneous hypertensive rats.
AB  - Ventricular remodeling is associated with many heart diseases, and ventricular
      remodeling induced by hypertension can be fatal independent of hypertension. In
      this study, we prepared a novel apitherapy formulation, designated Bao-Yuan-Ling
      (BYL), which contained propolis, royal jelly, and bee venom, to treat spontaneous
      hypertensive rats (SHRs). We then evaluated the pharmacology of BYL and the
      potential mechanisms through which BYL affects hypertension and ventricular
      remodeling. We found that BYL treatment could reduce blood pressure in SHRs.
      Thereafter, we found that BYL treatment reduced serum levels of angiotensin II,
      endothelin 1, and transforming growth factor-beta and improved the myocardial
      structure. Moreover, the results of quantitative real-time polymerase chain
      reaction indicated that BYL treatment could upregulate the mRNA expression of
      peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma. Thus, we
      could conclude that BYL had hypotensive and cardioprotective effects in SHRs,
      potentially through improvement of myocardial energy metabolism.

PMID- 29472768
TI  - Effect of Zhen Qi Fu Zheng granules on the bone marrow depression model induced
      by Zidorf.
AB  - Zidorf is a commonly used drug for the treatment of AIDS, the most common side
      effects of AZT was bone marrow depression. Therefore, we investigated the effects
      of Zhen Qi Fu Zheng (AQFZ) granules on the model of bone marrow depression
      induced by AZT. We showed that the high, medium and low doses of AQFZ granules
      could increase the number of WBC in the mice model induced by AZT, and the
      difference was significant (P < 0.01) compared with the model group. Each dose of
      AQFZ granules can increase the thymus cortex thickness, the number of thymus
      lymphocytes, spleen nodule size, the number of lymphocytes in the spleen (P <
      0.01). The medium dose of AQFZ granules can also significantly improve the number
      of BMC in the bone marrow depression model (P < 0.01). As well as, the low dose
      of AQFZ granules can clearly increase the number of nucleated cells in a bone
      marrow (P < 0.05) and IL-2blood serum. So, AQFZ granules can improve and regulate
      the hemogram, bone marrow and immune level of bone marrow depression model
      induced by AZT.

PMID- 29472769
TI  - The mechanisms and process of acephate degradation by hydroxyl radical and
      hydrated electron.
AB  - The degradation process of acephate in aqueous solution with *OH and [Formula:
      see text] produced by 60Co-gamma irradiation and electron pulse radiolysis was
      studied in the present paper. In the aqueous solution, acephate reacted with
      [Formula: see text] and transformed to transient species which can absorb weakly
      in the wavelength range of 300-400 nm and decay very fast. According to the decay
      of hydrated electron, the reaction rate constant of [Formula: see text] and
      acephate is (3.51 +/- 0.076) * 109 dm3.mol-1.s-1. The transient species produced
      in the reaction of *OH and acephate do not distinctly absorb the light in the
      wavelength range of 300-700 nm, so the decay and kinetics of the transient
      species cannot determinedirectly. The competing reaction of KSCN oracephate with
      *OH were studied to obtain the reaction rate constant of *OH and acephate, which
      is (9.1 +/- 0.11) * 108 dm3.mol-1.s-1. Although acetylamide and inorganic ions
      were determined in the products of the reaction of acephate with *OH or [Formula:
      see text], the concentration of inorganic ions in the products of the reaction of
      acephate with *OH is higher than that in the product of the reaction of acephate
      with [Formula: see text]. Moreover, there were sulfide in the products of the
      reaction of acephatewith [Formula: see text]. The degradation pathways of
      acephate by *OH and [Formula: see text] were also proposed based on the products
      from GC-MS.

PMID- 29472770
TI  - Study on biomolecules in extractives of Camellia oleifera fruit shell by GC-MS.
AB  - This study aims to present an integrated process that can be used to produce
      biomedical and biological active components from the fruit shell of Camellia
      oleifera Abel. Through the Foss method, Aldehyde, acid compounds, acyl and
      alcohol compounds account for 22.7, 15.93, 0.24 and 61.13% of the extractives
      which were extracted from Camellia oleifera fruit shell by methanol solvents.
      Furfural, Pyrazole-4-carboxaldehyde, 1-methyl- and 5-Hydroxymethylfurfural
      account for 4.74, 1.22 and 58.78% of the extractives which were extracted from
      the fruit shell of Camellia oleifera Abel by ethanol solvents. Aldehyde, acid and
      amine compounds account for 5.01, 56.18 and 7.20% of the extractives which were
      extracted from the fruit shell of Camellia oleifera Abel by ethyl acetate
      solvents. The extractives of fresh flesh of bayberry were rich in rare drug,
      biomedical and biological activities.

PMID- 29472771
TI  - A security mechanism based on evolutionary game in fog computing.
AB  - Fog computing is a distributed computing paradigm at the edge of the network and
      requires cooperation of users and sharing of resources. When users in fog
      computing open their resources, their devices are easily intercepted and attacked
      because they are accessed through wireless network and present an extensive
      geographical distribution. In this study, a credible third party was introduced
      to supervise the behavior of users and protect the security of user cooperation.
      A fog computing security mechanism based on human nervous system is proposed, and
      the strategy for a stable system evolution is calculated. The MATLAB simulation
      results show that the proposed mechanism can reduce the number of attack
      behaviors effectively and stimulate users to cooperate in application tasks
      positively.

PMID- 29472772
TI  - Effects of Decitabine on the proliferation of K562 cells and the expression of
      DR4 gene.
AB  - Objective: To investigate the role of DR4 gene in the occurrence, development and
      prognosis of acute myeloid leukemia (AML), find a new regulatory gene of
      Decitabine for the treatment of AML, namely DR4 gene, and explore the molecular
      mechanism of AML in the treatment of AML. Methods: The methylation level and the
      mRNA expression level of DR4 gene promoters of bone marrow mononuclear cells in
      122 patients with newly diagnosed AML and 24 patients with iron deficiency anemia
      (IDA) were detected using Methylation specific PCR (MS-PCR) and Q-RT-PCR,
      respectively, and a correlation analysis of them was conducted. The effects of
      Decitabine on the proliferation of K562 cells were detected using CCK-8 assay.
      Then, the effects of Decitabine on the methylation level and the mRNA expression
      level of DR4 genes of K562 cells treated with Decitabine were detected using MS
      PCR and Q-RT-PCR, respectively. The effects of Decitabine on the cell cycle and
      apoptosis of K562 cells were detected using flow cytometry. Results: Compared
      with the control group, the methylation level (P = .002) of DR4 genes of bone
      marrow mononuclear cells in patients with newly diagnosed AML was high. The
      methylation level (P = .01) of DR4 genes of bone marrow mononuclear cells in
      patients of the positive group of enlargement of liver, spleen and lymph node was
      lower than that of the negative group, and the methylation level (P = .006) of
      DR4 genes in patients of the high risk group of clinical stage was lower than
      that of the low risk group, and the methylation level (P = .03) of DR4 genes in
      patients of the group where patients did not achieve complete remission (CR1)
      after a course of induction chemotherapy was lower than that of the group where
      patients achieved complete remission (CR1) after a course of induction
      chemotherapy. There was a significant negative correlation (P < .01) between the
      methylation level and the mRNA expression level of DR4 genes of bone marrow
      mononuclear cells in 122 patients with newly diagnosed AML. After the K562 cells
      were treated with Decitabine for 48 h, the methylation level of DR4 gene
      promoters gradually decreased, while the mRNA expression level of DR4 genes
      gradually increased, both of which showed a concentration-dependent relationship.
      After the K562 cells were treated with 5 umol/L Decitabine for 48 h, the K562
      cells in G0/G1 phase and G2/M phase increased significantly, and the K562 cells
      in S phase decreased significantly. Conclusion: DR4 gene played an important role
      in the occurrence and development of AML. Decitabine can effectively inhibit the
      proliferation of K562 cells, which probably partly because it can terminate the
      methylation effect of DR4 gene promoters and restore the mRNA expression of DR4
      genes.

PMID- 29472773
TI  - Effects of age on slaughter performance and meat quality of Binlangjang male
      buffalo.
AB  - Twelve representative buffalo were selected from 22 suckling calves, 41 weaned
      calves, 57 reserve bulls and 20 adult bulls for slaughter. The study aims to
      assess the effect of age on dressing percentage, meat percentage and carcass meat
      yield and physico-chemical properties of longissimus dorsi and biceps femoris,
      and to evaluate the correlation between live weight and marbling, backfat
      thickness, rib eye area. The results showed that the slaughter performance and
      meat quality of Binlangjang male buffalo showed an obvious change with age. The
      dressing percentage decreased from 54.93% to 51.22% with the increase of age,
      while meat percentage and carcass meat yield increased gradually with age, which
      were 34.58-38.59%, 62.95-75.34%; Marbling, backfat thickness and rib eye area
      increased with age, and there was significant difference between the situation
      before 3 months and after 12 months of age (P < 0.05). The moisture content was
      maximum at birth, which then gradually decreased, but the difference was
      insignificant (P > 0.05). The levels of fat, protein, cholesterol and inosine
      acid were significantly different before 3 months of age from those after 12
      months (P < 0.05). Cholesterol content was negatively correlated with age, the
      minimum was 80.25 mg/100 g; Inosine acid content increased with age, reaching
      133.11 mg/100 g. Marbling, backfat thickness, rib eye area had a high correlation
      with live weight, with correlation coefficients respectively at 0.9096, 0.9291,
      0.9551. Based on the prediction model of live weight, Buffaloes was suitable for
      slaughtering for superior slaughter performance and meat quality after 24 months
      of age.

PMID- 29472774
TI  - 5,7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats
      through increase in the expression of heat shock protein-70 and inhibition of
      monoamine oxidase-A levels.
AB  - The current study was aimed to investigate the role of 5,7-dimethoxycoumarin in
      the prevention of chronic mild stress induced depression in rats. The chronic
      mild stress rat model was prepared using the known protocols. The results from
      open-field test showed that rats in the chronic mild stress group scored very low
      in terms of crossings and rearings than those of the normal rats. However, pre
      treatment of the rats with 10 mg/kg doses of 5,7-dimethoxycoumarin prevented
      decline in the locomotor activity by chronic mild stress. The level of monoamine
      oxidase-A in the chronic mild stress rat hippocampus was markedly higher. Chronic
      mild stress induced increase in the monoamine oxidase-A level was inhibited by
      pre-treatment with 10 mg/kg doses of 5,7-dimethoxycoumarin in the rats. Chronic
      mild stress caused a marked increase in the level of caspase-3 mRNA and proteins
      in rat hippocampus tissues. The increased level of caspase-3 mRNA and protein
      level was inhibited by treatment of rats with 5,7-dimethoxycoumarin (10 mg/kg).
      5,7-Dimethoxycoumarin administration into the rats caused a marked increase in
      the levels of heat shock protein-70 mRNA and protein. The levels of heat shock
      protein-70 were markedly lower both in normal and chronic mild stress groups of
      rats compared to the 5,7-dimethoxycoumarin treated groups. Thus 5,7
      dimethoxycoumarin prevented the chronic mild stress induced depression in rats
      through an increase in the expression of heat shock protein-70 and inhibition of
      monoamine oxidase-A levels.

PMID- 29472775
TI  - Resveratrol, an antioxidant, protects spinal cord injury in rats by suppressing
      MAPK pathway.
AB  - Resveratrol, a polyphenol found in various plants, including grapes, plums and
      peanuts has shown various medIRInal properties, including antioxidant, protection
      of cardiovascular disease and cancer risk. However, the effects of resveratrol on
      spinal cord reperfusion injury have not been investigated. Hence, the present
      study was designed to evaluate the effect of resveratrol on nitric oxide synthase
      (iNOS)/p38MAPK signaling pathway and to elucidate its regulating effect on the
      protection of spinal cord injury. Spinal cord ischemia-reperfusion injury (IRI)
      was performed by the infrarenal abdominal aorta with mini aneurysm clip model.
      The expressions of iNOS and p38MAPK and the levels of biochemical parameters,
      including nitrite/nitrate, malondialdehyde (MDA), advanced oxidation products
      (AOPP), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)
      were measured in control and experimental groups. IRI-induced rats treated with
      10 mg/kg resveratrol protected spinal cord from ischemia injury as supported by
      improved biological parameters measured in spinal cord tissue homogenates. The
      resveratrol treatment significantly decreased the levels of plasma
      nitrite/nitrate, iNOS mRNA and protein expressions and phosphorylation of p38MAPK
      in IRI-induced rats. Further, IRI-produced free radicals were reduced by
      resveratrol treatment by increasing enzymatic and non-enzymatic antioxidant
      levels such as GSH, SOD and CAT. Taken together, administration of resveratrol
      protects the damage caused by spinal cord ischemia with potential mechanism of
      suppressing the activation of iNOS/p38MAPK pathway and subsequent reduction of
      oxidative stress due to IRI.

PMID- 29472776
TI  - Tanshinone IIA suppress the proliferation of HNE-1 nasopharyngeal carcinoma an in
      vitro study.
AB  - Nasopharyngeal carcinoma (NPC) at present is considered to be one of the fatal
      diseases detected commonly in the people belonging to Southeast Asia and southern
      China. According to the WHO reports among the detected cases of NPC worldwide,
      80% are from China. The present study investigates the effect of tanshinone IIA
      on the migration and invasion potential of HNE-1NPC cells and studied the
      detailed mechanism involved. Effect of the tanshinone IIA on viability of the HNE
      1NPC cells was analyzed by MTS assay. Cell matrigel invasion and wound-healing
      motility assays, respectively were used for the analysis of invasion and
      migration potential of HNE-1 cells. Tanshinone IIA inhibited the viability of HNE
      1cells in a dose dependent manner. Migration and invasion potential of the
      tanshinone IIA treated cells was reduced significantly (P < 0.05) compared to the
      control cells after 48 h. Analysis of the proteins involved in migration and
      invasion revealed a significant decrease in the expression of matrix
      metalloproteinase (MMP)-2 and MMP-9 on treatment with tanshinone IIA. It also
      inhibited the p65 and p50 expression in the nuclear fractions of HNE-1 cells
      after 48 h. Thus, tanshinone IIA inhibits migration and invasion potential of the
      HNE-1NPC cells through reduction in the expression of matrix metalloproteinases.
      Therefore, tanshinone IIA can be used for the treatment of NPC.

PMID- 29472777
TI  - Auxin-cytokinin synergism in vitro for producing genetically stable plants of
      Ruta graveolens using shoot tip meristems.
AB  - An efficient micropropagation protocol was developed for Ruta graveolens Linn.
      using shoot tip meristems derived from a 4-month-old field grown plant. In vitro
      shoot regeneration and proliferation was accomplished on Murashige and Skoogs
      (MS) semi-solid medium in addition to different doses of cytokinins viz.6- benzyl
      adenine (BA), Kinetin (Kn) or 2-isopetynyl adenine (2iP), singly or in
      combination with auxins viz. indole-3-acetic acid (IAA), indole-3-butyric acid
      (IBA) or alpha-naphthalene acetic acid (NAA). Highest regeneration frequency
      (27.6%) was obtained on (MS) medium composed of BA (10 uM) with maximum number
      (9.4) of shoots and 4.3 cm shoot length after 4 weeks of incubation. Among
      various combinations tried best regeneration frequency (71%) of multiple shoot
      formation with highest number (12.6) of shoots per shoot tip explants were
      achieved in MS medium augmented with a combination BA (10.0 uM) and NAA (2.5 uM)
      after 4 weeks of incubation. The optimum frequency (97%) of rhizogenesis was
      achieved on half-strength MS medium having 0.5 uM IBA after 4 weeks of
      incubation. Tissue culture raised plantlets with 5-7 fully opened leaves with
      healthy root system were successfully acclimatized off in SoilriteTM with 80%
      survival rate followed by transportation to normal soil under natural light.
      Genetic stability among in vitro raised progeny was evaluated by ISSR and RAPD
      markers. The entire banding pattern revealed from in vitro regenerated plants was
      monomorphic to the donor. The present protocol provides an alternative option for
      commercial propagation and fruitful setting up of genetically uniform progeny for
      sustainable utilization and germplasm preservation.

PMID- 29472778
TI  - Deleterious effects of potassium bromate administration on renal and hepatic
      tissues of Swiss mice.
AB  - Potassium bromate (KBrO3) is widely used as a food additive and is a major water
      disinfection by-product. The present study reports the side effects of KBrO3
      administration in Swiss mice. Animals were randomly divided into three groups:
      control, low dose KBrO3 (100 mg/kg/day) and high dose KBrO3 (200 mg/kg/day)
      groups. Administration of KBrO3 led to decreased white blood corpuscles (WBCs),
      red blood corpuscles (RBCs) and platelets count in the animals of both the high
      and the low dose groups. Altered lipid profile represented as low density
      lipoprotein (LDL), high density lipoprotein (HDL) and cholesterol levels were
      observed in plasma samples of both KBrO3 treated groups of mice. Also, an
      increased plasma level of LDH was detected in both KBrO3 treated groups.
      Histological investigations showed impaired renal and hepatic histology that was
      concomitant with increased plasma Creatinine level in both of KBrO3-treated
      groups. Nevertheless, decreased glutathione (GSH) level in both renal and hepatic
      tissue of mice after KBrO3 intake was detected. These results show that KBrO3 has
      serious damaging effects and therefore, its use should be avoided.

PMID- 29472780
TI  - Conservation in Saudi Arabia; moving from strategy to practice.
AB  - Conservation in the Kingdom of Saudi Arabia is relatively young, yet have made
      considerable gains in conservation through strategic proclamation and
      reintroductions. Changes in land use, illegal hunting and competition with
      domestic stock has decimated the native ungulates, meaning that the survival of
      the native ungulate species is now completely dependent on protected area
      network. The challenge is to sustain this network to make meaningful conservation
      impact into the future. We review the status of ungulate conservation in Saudi
      Arabia and highlight that the conservation strategy is well developed. The major
      challenge faced in conservation in Saudi Arabia now is to implement what has been
      sanctioned.

PMID- 29472779
TI  - Effect of PEG-6000 imposed drought stress on RNA content, relative water content
      (RWC), and chlorophyll content in peanut leaves and roots.
AB  - Drought, one of the environmental stresses, plays crucial role in reduction in
      plant production on majority of agricultural fields of world, In order to
      evaluate drought stress on RNA content Relative water content (RWC), and
      chlorophyll content, Water deficit was induced by Polyethylene glycol (PEG) in
      peanut (Arachis hypogaea), accession number ICGV 91114. In this current study we
      evaluate RNA content and Relative water content (RWC) both in leaves and roots
      and chlorophyll content in leaf. The present study was undertaken with the aim to
      investigate the effect of water deficit imposed by PEG-6000, 40 old day seedlings
      were treated with varying concentrations of polyethylene glycol-6000 (PEG-6000;
      w/v-5%, 10%, 15% & 20%) for 24 h. The results showed that RNA content and
      Relative water content (RWC) content was significantly reduced in both leaves and
      roots with increased concentration of PEG, In leaves, a concentration dependent
      decline in chlorophyll content with increasing concentration of polyethylene
      glycol-6000 (PEG-6000). Reduction in chlorophyll 'a' level was to a greater
      extent than the chlorophyll 'b'. Thus, this attributes can be used as screening
      tool for drought tolerance in peanut.

PMID- 29472781
TI  - Evaluation of traditional medicinal plant, Cissus setosa Roxb. (Vitaceae) for
      antiulcer property.
AB  - Cissus setosa is an indigenous medicinal herb commonly used for the treatment of
      gastro ulcers. In the current investigation the aerial methanolic extract of C.
      setosa was investigated for their antiulcer activity using pylorus ligation and
      ethanol in experimental rats. The extract was administered at the doses of 200
      and 400 mg/kg b.w. orally for 3 days. However, higher dose of the extract
      subsequently reduced gastric ulcer induced aberrations by pylorus ligation
      (70.05%) and ethanol (78.16%) as judged by their altered biochemical parameters
      such as free acidity, total acidity, total carbohydrate, total protein and pepsin
      activity. Furthermore, macroscopic examination of rat's stomach also showed that
      the pretreatment with methanolic extract notably lowered the pylorus ligation and
      ethanol induced ulcers. As perceived in the present study, evidently, our
      findings basically supports the potency of the methanol extracts of C. setosa to
      treat gastrointestinal related disorders, thus lends pharmacological credence to
      the suggested folklore use.

PMID- 29472782
TI  - Grafting improves cucumber water stress tolerance in Saudi Arabia.
AB  - Water scarcity is a major limiting factor for crop productivity in arid and semi
      arid areas. Grafting elite commercial cultivars onto selected vigorous rootstocks
      is considered as a useful strategy to alleviate the impact of environmental
      stresses. This study aims to investigate the feasibility of using grafting to
      improve fruit yield and quality of cucumber under water stress conditions.
      Alosama F1 cucumber cultivar (Cucumis sativus L.) was grafted onto Affyne
      (Cucumis sativus L.) and Shintoza A90 (Cucurbitamaxima * C. moschata) rootstocks.
      Non-grafted plants were used as control. All genotypes were grown under three
      surface drip irrigation regimes: 50%, 75% and 100% of the crop evapotranspiration
      (ETc), which represent high-water stress, moderate-water stress and non-water
      stress conditions, respectively. Yield and fruit quality traits were analyzed and
      assessed. In comparison to the non-grafted plants, the best grafting treatment
      under water stress was Alosama F1 grafted onto Shintoza A90 rootstock. It had an
      overall improved yield and fruit quality under water stress owing to an increase
      in the total fruit yield by 27%, from 4.815 kg plant-1 in non-grafted treatment
      to 6.149 kg plant-1 in grafted treatment under moderate -water stress, total
      soluble solid contents (13%), titratable acidity (39%) and vitamin C (33%). The
      soil water contents were low in soil surface and increase gradually with soil
      depth, while salt distribution showed an adverse trend. The positive effects of
      grafting on plant growth, productivity, and water use efficiency support this
      strategy as an useful tool for improving water stress tolerance in greenhouse
      grown cucumber in Saudi Arabia.

PMID- 29472783
TI  - Performance evaluation of Chrysopogon zizanoides under urban conditions of
      Kuwait.
AB  - Plant physiological and morphological attributes should be critically evaluated
      for selecting any species for landscaping projects. The selection of a species
      should be based on the evaluation of its adaptability, noninvasiveness, growth
      potential, and performance under the prevailing local arid conditions for their
      aesthetic looks, soil stabilization, and afforestation values. Chrysopogon
      zizanoides (Vetiver), is suitable for Kuwait because it can withstand fluctuating
      temperatures ranging from -14 to 55  degrees C with unique physical and
      physiological characteristics. Despite the successful growth performance of
      Vetiver in landscaping projects mostly in several tropical countries, it has not
      been utilized and evaluated in the Arabian Gulf region. The objective of the
      current study was to evaluate the performance of selected ten cultivars of
      Vetiver (ODV-1, 8, 9, 13, 17, 21, 23, Silent Valley, Urlikal, and Pannimedu) in
      the deficient soil and environmental conditions of Kuwait in urban landscape at
      minimal maintenance. It is suggested that based on visual greenery effect and
      overall growth performance cultivars, Pannimedu, Silent Valley, ODV-13, ODV-8 and
      ODV-9 can be considered for landscaping projects in Kuwait. To obtain the
      superior crown volume (which considers height and canopy) cultivar Pannimedu is
      suggested and to get a bushy growth (considering the number of tillers) cultivar
      ODV-13 and ODV-8 is found to be suitable.

PMID- 29472784
TI  - Preparation, characterization of silver phyto nanoparticles and their impact on
      growth potential of Lupinus termis L. seedlings.
AB  - The current study reports rapid and easy method for synthesis of eco-friendly
      silver nanoparticles (AgNPs) using Coriandrum sativum leaves extract as a
      reducing and covering agent. The bio-reductive synthesis of AgNPs was monitored
      using a scanning double beam UV-vis spectrophotometer. Transmission electron
      microscopy (TEM) was used to characterize the morphology of AgNPs obtained from
      plant extracts. X-ray diffraction (XRD) patterns of AgNPs indicate that the
      structure of AgNPs is the face centered cubic structure of metallic silver. The
      surface morphology and topography of the AgNPs were examined by scanning electron
      microscopy and the energy dispersive spectrum revealed the presence of elemental
      silver in the sample. The silver phyto nanoparticles were collected from plant
      extract and tested growth potential and metabolic pattern in (Lupinus termis L.)
      seedlings upon exposure to different concentrations of AgNPs. The seedlings were
      exposed to various concentrations of (0, 0.1, 0.3 and 0.5 mg L-1) AgNPs for ten
      days. Significant reduction in shoot and root elongation, shoot and root fresh
      weights, total chlorophyll and total protein contents were observed under the
      higher concentrations of AgNPs. Exposure to 0.5 mg L-1 of AgNPs decreased sugar
      contents and caused significant foliar proline accumulation which considered as
      an indicator of the stressful effect of AgNPs on seedlings. AgNPs exposure
      resulted in a dose dependent decrease in different growth parameters and also
      caused metabolic disorders as evidenced by decreased carbohydrates and protein
      contents. Further studies needed to find out the efficacy, longevity and toxicity
      of AgNPs toward photosynthetic system and antioxidant parameters to improve the
      current investigation.

PMID- 29472786
TI  - Exploration and local utilization of medicinal vegetation naturally grown in the
      Deusai plateau of Gilgit, Pakistan.
AB  - In the study area, the traditional knowledge regarding the uses of local wild
      medicinal plants for the health care of human and domestic animals is totally in
      hold of old people. The young ones are unaware about such an indispensable
      practices. The objective of the current study was to transfer this sort of
      precious knowledge from old members of the community to young generations in
      documented form.

PMID- 29472785
TI  - Honey: Single food stuff comprises many drugs.
AB  - Honey is a natural food item produced by honey bees. Ancient civilizations
      considered honey as a God gifted prestigious product. Therefore, a huge
      literature is available regarding honey importance in almost all religions.
      Physically, honey is a viscous and jelly material having no specific color.
      Chemically, honey is a complex blend of many organic and inorganic compounds such
      as sugars, proteins, organic acids, pigments, minerals, and many other elements.
      Honey use as a therapeutic agent is as old as human civilization itself. Prior to
      the appearance of present day drugs, honey was conventionally used for treating
      many diseases. At this instant, the modern research has proven the medicinal
      importance of honey. It has broad spectrum anti-biotic, anti-viral and anti
      fungal activities. Honey prevents and kills microbes through different mechanism
      such as elevated pH and enzyme activities. Till now, no synthetic compound that
      works as anti-bacterial, anti-viral and anti-fungal drugs has been reported in
      honey yet it works against bacteria, viruses and fungi while no anti-protozoal
      activity has been reported. Potent anti-oxidant, anti-inflammatory and anti
      cancerous activities of honey have been reported. Honey is not only significant
      as anti-inflammatory drug that relieve inflammation but also protect liver by
      degenerative effects of synthetic anti-inflammatory drugs. This article reviews
      physico-chemical properties, traditional use of honey as medicine and mechanism
      of action of honey in the light of modern scientific medicinal knowledge.

PMID- 29472787
TI  - Kinetics and mathematical modeling of infrared thin-layer drying of garlic
      slices.
AB  - Drying of garlic slices in thin-layer have been studied with Infrared (IR) at
      0.075, 0.15, 0.225 and 0.3 W cm-2 radiation intensity and 0.75 and 1.25 m s-1 air
      flow velocity. The results showed increasing in drying rate and decreasing at the
      time of drying with decreasing air flow velocity and increasing IR radiation
      intensity. The effective moisture diffusivity (Deff) was obtained using Fick's
      diffusion equation and its mean values ranged between 5.83*10-11 and 7.66*10-10
      m2 s-1 for all investigated conditions. In addition, a third-order polynomial
      equation linking the effective moisture diffusivity and moisture content was
      found. Average activation energy increased with the decrease of IR radiation and
      increase of air flow velocity. Thirteen different mathematical models were
      verified with non-linear regression analysis for describing the garlic drying
      process. Modified Henderson and Pabis model presented the best prediction of the
      drying of garlic slices.

PMID- 29472788
TI  - Impact of pH and butyric acid on butanol production during batch fermentation
      using a new local isolate of Clostridium acetobutylicum YM1.
AB  - The effect of pH and butyric acid supplementation on the production of butanol by
      a new local isolate of Clostridium acetobutylicum YM1 during batch culture
      fermentation was investigated. The results showed that pH had a significant
      effect on bacterial growth and butanol yield and productivity. The optimal
      initial pH that maximized butanol production was pH 6.0 +/- 0.2. Controlled pH
      was found to be unsuitable for butanol production in strain YM1, while the
      uncontrolled pH condition with an initial pH of 6.0 +/- 0.2 was suitable for
      bacterial growth, butanol yield and productivity. The maximum butanol
      concentration of 13.5 +/- 1.42 g/L was obtained from cultures grown under the
      uncontrolled pH condition, resulting in a butanol yield (YP/S ) and productivity
      of 0.27 g/g and 0.188 g/L h, respectively. Supplementation of the pH-controlled
      cultures with 4.0 g/L butyric acid did not improve butanol production; however,
      supplementation of the uncontrolled pH cultures resulted in high butanol
      concentrations, yield and productivity (16.50 +/- 0.8 g/L, 0.345 g/g and 0.163
      g/L h, respectively). pH influenced the activity of NADH-dependent butanol
      dehydrogenase, with the highest activity obtained under the uncontrolled pH
      condition. This study revealed that pH is a very important factor in butanol
      fermentation by C. acetobutylicum YM1.

PMID- 29472789
TI  - Effect of different proportion of sulphur treatments on the contents of
      glucosinolate in kale (Brassica oleracea var. acephala) commonly consumed in
      Republic of Korea.
AB  - Kale (Brassica oleracea L. Acephala Group) is the rich source of medicinal value
      sulphur compounds, glucosinolates (GLSs). The aim of this study was to
      investigate the effect of different proportion of sulphur (S) supplementation
      levels on the accumulation of GLSs in the leaves of the kale cultivar ('TBC').
      High performance liquid chromatography (HPLC) separation method guided to
      identify and quantify six GSLs including three aliphatic (progoitrin, sinigrin
      and gluconapin) and three indolyl (glucobrassicin, 4-methoxyglucobrassicin and
      neoglucobrasscin) respectively. Analysis of these distinct levels of S
      supplementation revealed that the accumulation of individual and total GLSs was
      directly proportional to the S concentration. The maximum levels of total GLSs
      (26.8 umol/g DW) and glucobrassicin (9.98 umol/g DW) were found in lower and
      upper parts of the leaves supplemented with 1 mM and 2 mM S, respectively.
      Interestingly, aliphatic GSLs were noted predominant in all the parts (50.1, 59.3
      and 56% of total GSLs). Among the aliphatic and indolyl GSLs, sinigrin and
      glucobrassicin account 35.3 and 30.88% of the total GSLs. From this study, it is
      concluded that supply of S enhance the GSLs accumulation in kale.

PMID- 29472790
TI  - Pollen morphology of certain species of the family Lamiaceae in Saudi Arabia.
AB  - The intention of the present wok is to provide an account on the pollen
      morphological features of Lamiaceae in Saudi Arabia as a basis for future studies
      of Lamiaceae pollens in the region. Pollen morphology of 20 species belong to 16
      genera of the Lamiaceae has been investigated using Light Microscope (LM) and
      Scanning Electron Microscope (SEM). The study revealed that the pollen grains
      were characterized by 3-zonocolpate or 6-zonocolpate. Size of the pollen is
      variable between the genera but not among the species of the same genus. The
      surface pattern of the exine varies from fine reticulate, rough reticulate, mega
      reticulate, reticulate-perforate, bireticulate-perforate or granulate, leading to
      6 types of pollen grains. These variations revealed by this study implies that
      pollen Morphology may be of significant value sharing in solving problems in the
      classification of Lamiaceae members. A Key to the species, based on the
      morphological features of pollen grains, is also provided.

PMID- 29472791
TI  - Antimicrobial activity of some plant extracts against bacterial strains causing
      food poisoning diseases.
AB  - Prevention of food spoilage and food poisoning pathogens is usually achieved by
      use of chemical preservatives which have negative impacts including: human health
      hazards of the chemical applications, chemical residues in food & feed chains and
      acquisition of microbial resistance to the used chemicals. Because of such
      concerns, the necessity to find a potentially effective, healthy safer and
      natural alternative preservatives is increased. Within these texts, Plant
      extracts have been used to control food poisoning diseases and preserve
      foodstuff. Antimicrobial activity of five plant extracts were investigated
      against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas
      aeruginosa and Salmonella typhi using agar disc diffusion technique. Ethanolic
      extracts of Punica granatum, Syzygium aromaticum, Zingiber officinales and Thymus
      vulgaris were potentially effective with variable efficiency against the tested
      bacterial strains at concentration of 10 mg/ml while extract of Cuminum cyminum
      was only effective against S. aureus respectively. P. granatum and S. aromaticum
      ethanolic extracts were the most effective plant extracts and showed
      bacteriostatic and bactericidal activities against the highly susceptible strains
      of food borne pathogenic bacteria (S. aureus and P. aeruginosa) with MIC's ranged
      from 2.5 to 5.0 mg/ml and MBC of 5.0 and 10 mg/ml except P. aeruginosa which was
      less sensitive and its MBC reached to 12.5 mg/ml of S. aromaticum respectively.
      These plant extracts which proved to be potentially effective can be used as
      natural alternative preventives to control food poisoning diseases and preserve
      food stuff avoiding healthy hazards of chemically antimicrobial agent
      applications.

PMID- 29472792
TI  - Can clusters based on caries experience and medical status explain the
      distribution of overhanging dental restorations and recurrent caries? A cross
      sectional study in Madinah - Saudi Arabia.
AB  - Background: Overhanging dental restorations (ODRs) and secondary caries lesions
      (SCLs) are of high prevalence and jeopardize the fate of the restoration.
      Objectives: To assess the relationship between ODRs, SCLs and certain caries
      contributory factors. Methods: A total of 502 radiographic records of dental
      patients with proximal fillings (mean age 38 +/- 13 years, 50% females) were
      screened for ODRs and SCLs. Descriptive and inferential statistics were used. In
      addition, two-step cluster analysis was performed in an attempt to explain trends
      in ODR and SCL distribution. A p value of <= 0.05 was considered statistically
      significant. Results: More than 30% of the individuals had ODRs and SCLs. No
      differences between genders were observed (p > 0.05). Individuals with medical
      conditions had more ODRs than those without (49% vs. 34%, p <= 0.05), while those
      with high caries experience had more SCLs (49%, p <= 0.05). The cluster analysis
      grouped the participants in five clusters, with the cluster involving individuals
      with no medical conditions and low caries experience demonstrating the lowest
      prevalence of ODRs and SCLs. Conclusions: Within the study limits, more than one
      third of the sample of dental patients had ODRs and SCLs. The medical condition
      was associated with ODRs, while the past caries experience was associated with
      SCLs.

PMID- 29472793
TI  - Dihydroartemisinin inhibits colon cancer cell viability by inducing apoptosis
      through up-regulation of PPARgamma expression.
AB  - The present study was aimed to investigate the effect of dihydroartemisinin on
      the colon cancer cell proliferation and apoptosis. The results from MTT assay
      revealed a concentration and time dependent relation between the inhibition of SW
      948 cell viability and dihydroartemisinin addition. The viability of SW 948 cells
      was reduced to 45 and 24% on treatment with 30 and 50 uM, respectively
      concentrations of dihydroartemisinin after 48 h. Morphological examination of SW
      948 cells showed attainment of rounded shape and cluster formation on treatment
      with dihydroartemisinin. Western blot analysis showed a significant increase in
      the activation of caspase-3 and expression of cleaved PARP by dihydroartemisinin
      treatment. The activation of PPARgamma was increased significantly in SW 948
      cells by treatment with dihydroartemisinin. Compared to control, the migration
      potential of SW 948 cells was reduced significantly (p < 0.005) and the
      expression levels of MMP-2 and -9 inhibited by dihydroartemisinin at 50 uM
      concentration. In the dihydroartemisinin treatment group colon tumor formation
      was significantly inhibited on treatment with 20 mg/kg doses of
      dihydroartemisinin after 30 days. Therefore, dihydroartemisinin inhibits colon
      cancer growth by inducing apoptosis and increasing the expression of PPARgamma.
      Thus dihydroartemisinin can be used for the treatment of colon cancer.

PMID- 29472794
TI  - Validation of botanical origins and geographical sources of some Saudi honeys
      using ultraviolet spectroscopy and chemometric analysis.
AB  - This study aims at distinguishing honey based on botanical and geographical
      sources. Different floral honey samples were collected from diverse geographical
      locations of Saudi Arabia. UV spectroscopy in combination with chemometric
      analysis including Hierarchical Cluster Analysis (HCA), Principal Component
      Analysis (PCA), and Soft Independent Modeling of Class Analogy (SIMCA) were used
      to classify honey samples. HCA and PCA presented the initial clustering pattern
      to differentiate between botanical as well as geographical sources. The SIMCA
      model clearly separated the Ziziphus sp. and other monofloral honey samples based
      on different locations and botanical sources. The results successfully
      discriminated the honey samples of different botanical and geographical sources
      validating the segregation observed using few physicochemical parameters that are
      regularly used for discrimination.

PMID- 29472795
TI  - Effect of gut bacterial isolates from Apis mellifera jemenitica on Paenibacillus
      larvae infected bee larvae.
AB  - The probiotic effects of seven newly isolated gut bacteria, from the indegenous
      honey bees of Saudi Arabia were investigated. In vivo bioassays were used to
      investigate the effects of each gut bacterium namely, Fructobacillus fructosus
      (T1), Proteus mirabilis (T2), Bacillus licheniformis (T3), Lactobacillus kunkeei
      (T4), Bacillus subtilis (T5), Enterobacter kobei (T6), and Morganella morganii
      (T7) on mortality percentage of honey bee larvae infected with P. larvae spores
      along with negative control (normal diet) and positive control (normal diet
      spiked with P. larvae spores). Addition of gut bacteria to the normal diet
      significantly reduced the mortality percentage of the treated groups. Mortality
      percentage in all treated groups ranged from 56.67% up to 86.67%. T6 treated
      group exhibited the highest mortality (86.67%), whereas T4 group showed the
      lowest mortality (56.67%). Among the seven gut bacterial treatments, T4 and T3
      decreased the mortality 56.67% and 66.67%, respectively, whereas, for T2, T6, and
      T7 the mortality percentage was equal to that of the positive control (86.67%).
      Mortality percentages in infected larval groups treated with T1, and T5 were
      78.33% and 73.33% respectively. Most of the mortality occurred in the treated
      larvae during days 2 and 3. Treatments T3 and T4 treatments showed positive
      effects and reduced mortality.

PMID- 29472796
TI  - Characterization of gut bacterial flora of Apis mellifera from north-west
      Pakistan.
AB  - Gut microbiota has been recognized to play a beneficial role in honey bees (Apis
      mellifera). Present study was designed to characterize the gut bacterial flora of
      honey bees in north-west Pakistan. Total 150 aerobic and facultative anaerobic
      bacteria from guts of 45 worker bees were characterized using biochemical assays
      and 16S rDNA sequencing followed by bioinformatics analysis. The gut isolates
      were classified into three bacterial phyla of Firmicutes (60%), Proteobacteria
      (26%) and Actinobacteria (14%). Most of the isolates belonged to genera and
      families of Staphylococcus, Bacillus, Enterococcus, Ochrobactrum, Sphingomonas,
      Ralstonia, Enterobacteriaceae, Corynebacterium and Micrococcineae. Many of these
      bacteria were tolerant to acidic environments and fermented sugars, hence
      considered beneficial gut inhabitants and involved the maintenance of a healthy
      microbiota. However, several opportunistic commensals that proliferate in the
      hive environment including members Staphylococcus haemolyticus group and
      Sphingomonas paucimobilis were also identified. This is the first report on bee
      gut microbiota from north-west Pakistan geographically situated at the crossroads
      of Indian subcontinent and central Asia.

PMID- 29472797
TI  - Fish eco-genotoxicology: Comet and micronucleus assay in fish erythrocytes as in
      situ biomarker of freshwater pollution.
AB  - Owing to white meat production Labeo rohita have vast economic importance, but
      its population has been reduced drastically in River Chenab due to pollution.
      Atomic absorption spectrophotometry showed a merciless toxicity level of Cd, Cu,
      Mn, Zn, Pb, Cr, Sn and Hg. Comet assay results indicated significant (p < .05)
      DNA fragmentation in Labeo rohita as 42.21 +/- 2.06%, 31.26 +/- 2.41% and 21.84
      +/- 2.21% DNA in comet tail, tail moment as 17.71 +/- 1.79, 10.30 +/- 1.78 and
      7.81 +/- 1.56, olive moment as 13.58 +/- 1.306, 8.10 +/- 1.04 and 5.88 +/- 0.06,
      respectively, from three different polluted sites on the river. Micronucleus
      assay showed similar findings of single micronucleus induction (MN) as 50.00 +/-
      6.300/00, double MN 14.40 +/- 2.560/00, while nuclear abnormalities (NA) were
      found as 150.00 +/- 2.920/00. These higher frequencies of MN induction and NA
      were found to be the cause of reduction of 96% of the population of this fish
      species in an experimental area of the River Chenab. This fish species has been
      found near extinction through the length of the river Chenab and few specimens in
      rainy seasons if restored by flood, may die in sugarcane mill season. Due to
      sweeping extinction Labeo rohita showed the highest sensitivity for pollution and
      could be used as bioindicator and DNA fragmentation in this column feeder fish
      species as a biomarker of the pollution load in freshwater bodies.

PMID- 29472798
TI  - Plankton community and the relationship with the environment in saline lakes of
      Onon-Torey plain, Northeastern Mongolia.
AB  - The plankton community of sixteen saline lakes located on Onon-Torey plain
      (Northeastern Mongolia) during the filling phase and the raising of the water
      level was investigated in July 2011. Thirty-five taxa of phytoplankton and thirty
      one species of zooplankton were found. For phytoplankton, blue-green algae
      (Merismopedia elegans, Anabaenopsis elenkinii, Arthrospora fusiformis, Spirulina
      major, Lyngbya sp., Oscillatoria sp.) and green algae (Monoraphidium minutum,
      Tetrastrum komarekii, Ankyra ocellata, Oocystis sp.) were dominant. For
      zooplankton, Filinia longiseta, Brachionus plicatilis, B. variabilis, Hexarthra
      mira (Rotifera), Daphnia magna, Moina brachiata, M. mongolica (Cladocera),
      Arctodiaptomus bacillifer, Mixodiaptomus incrassatus, Metadiaptomus asiaticus
      (Copepoda) dominated. Mineralization, active hydrogen ratio, dissolved oxygen and
      water temperature were the main factors influencing the diversity, structure and
      distribution of plankton organisms in the steppe lakes during low water level.
      The RDA analysis for phytoplankton and zooplankton from different lakes was
      carried out for selected two groups which included lakes and a subset related
      species. The first group is of oligohaline and mesohaline lakes in which mostly
      green algae, rotifers and copepods inhabit. The second group is of mesohaline and
      polyhaline lakes with mainly blue-green algae, some crustaceans and rotifers
      inhabiting. High abundance and biomass of Spirulina major, Oscillatoria sp. and
      Brachionus variabilis were observed in lakes with high mineralization, pH and
      temperature.

PMID- 29472800
TI  - Biochemia Medica appoints new Editor-in-Chief and new Senior Editor.

PMID- 29472799
TI  - Setting the IMPACT (IMProve Access to Clinical Trial data) Observatory baseline.
AB  - Introduction: The aim of the IMPACT (IMProving Access to Clinical Trial data)
      Observatory is to assess the transformation of clinical trials (CT) related to
      the evolution of sharing of CT data. The objective of this study is to establish
      a baseline for monitoring CT data sharing by the Observatory. Materials and
      methods: In this scoping review we searched for publications that address
      sharing, dissemination, transparency or reuse of CT data published prior to
      December 31st 2000. Two authors screened titles and abstracts of 1204 records
      received by Medline searches and added 47 publications from direct discovery.
      Four researchers extracted, coded, and analyzed the predefined information from
      102 selected papers. Results: We found a growing recognition of the importance of
      data sharing prior to 2001. However, there were numerous obstacles including the
      ambiguity of the concept of data sharing, the absence of specific terminology and
      the lack of an "open" culture. By the end of 2000, data, metadata, and evidence
      based medicine were defined. Data sharing, registries, databases and re-analyses
      of individual patient data (IPD) emerged. The use of systematic reviews and IPD
      meta-analysis in decision making was promoted. Most arguments for broader data
      sharing came from oncology, paediatrics, rare diseases, AIDS, pregnancy,
      perinatal medicine, and media reporting related scandals. Conclusions: Our
      findings indicate that the year 2000 could be used as a baseline for monitoring
      the evolution of CT data sharing as basic prerequisites were set in place,
      including greater understanding that CT data sharing is essential for decision
      making and the advancements of the Internet.

PMID- 29472801
TI  - Diagnostic value of tumour markers in pleural effusions.
AB  - Introduction: We investigated whether tumour markers carcinoembryonic antigen
      (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA-125), and
      cytokeratin 19 fragment (CYFRA 21-1) in pleural effusions and serum can be used
      to distinguish pleural effusion aetiology. Materials and methods: During the
      first thoracentesis, we measured pleural fluid and serum tumour marker
      concentrations and calculated the pleural fluid/serum ratio for patients
      diagnosed with pleural effusion, using electrochemiluminescence immunoassays.
      Receiver operating characteristic (ROC) analysis was carried out and the Hanley
      and McNeil method was used to test the significance of the difference between the
      areas under ROC curves (AUCs). In order to detect which tumour marker best
      discriminates between malignant and non-malignant pleural effusions and to
      establish the predictive value of those markers, discriminant function analysis
      (DFA) and logistic regression analysis were utilized. Results: Serum tumour
      markers CYFRA 21-1 and NSE as well as pleural NSE were good predictors of pleural
      effusion malignancy and their combined model was found statistically significant
      (Chi-square = 28.415, P < 0.001). Respective ROC analysis showed significant
      discrimination value of the combination of these three markers (AUC = 0.79).
      Conclusions: Serum markers showed superiority to pleural fluid markers in
      determining pleural fluid aetiology. Serum CYFRA 21-1 and NSE concentrations as
      well as pleural fluid NSE values had the highest clinical value in
      differentiating between malignant and non-malignant pleural effusions. The
      combination of these three markers produced a significant model to resolve
      pleural effusion aetiology.

PMID- 29472802
TI  - Preanalytics of urine sediment examination: effect of relative centrifugal force,
      tube type, volume of sample and supernatant removal.
AB  - Introduction: Laboratories often modify procedures recommended by the European
      Urinalysis Guidelines for urine sediment analysis. The aim of this study was to
      compare the recommended protocol with our routine laboratory procedure and to
      evaluate the possible impact of modifications in the relative centrifugal force,
      type of tube, method of supernatant aspiration and urine volume on patient's
      results. Material and methods: Firstly, relative centrifugal force was
      investigated using 20 pairs of samples examined after centrifugation at 400xg and
      1358xg. In phase two, 110 samples were examined, paired as: round bottom vs
      conical tube (N = 46), decanting vs suction of supernatant (N = 100) and 10 mL vs
      5 mL of urine sample (N = 101). Results: The number of erythrocytes, leukocytes
      and squamous epithelial cells was significantly lower after centrifugation at
      400xg (P = 0.001, 0.002 and 0.004, respectively). The number of leukocytes was
      significantly lower in conical tubes (P = 0.010), after the suction of
      supernatant (P = 0.045) and in 5 mL urine (P < 0.001). The number of squamous
      epithelial cells was significantly lower after the suction of supernatant (P <
      0.001) and in 5 mL urine (P < 0.001). The number of erythrocytes (P < 0.001),
      total non-hyaline casts (P < 0.001) and the frequency of granular casts (P =
      0.039) was significantly lower in 5 mL urine. Conclusion: Lower results of
      leukocytes, erythrocytes, squamous cells and non-hyaline casts were recorded in
      recommended procedures (centrifugation at 400xg, suction of supernatant, conical
      tube, 5 mL of sample) than in routine procedure (centrifugation at 1358xg,
      decanting of supernatant, round bottom tube, 10 mL) used in our laboratory.

PMID- 29472803
TI  - Reference interval for immature platelet fraction on Sysmex XN haematology
      analyser in adult population.
AB  - Introduction: The Sysmex XN-series haematology analyser has newly adopted a
      fluorescent channel to measure immature platelet fraction (IPF). To promote the
      clinical utility of this promising parameter, establishing a reliable reference
      interval is mandatory. According to previous studies, IPF values may be affected
      by the employed analyser and the ethnic background of the individual, but no
      differences seem to be found between individuals' genders. Therefore, this study
      aimed to define the reference interval for IPF in a Spanish population following
      Clinical and Laboratory Standard Institute (CLSI) guidelines. Materials and
      methods: A total of 153 healthy Caucasian adults from Spain met the inclusion
      criteria. IPF measurement was performed by means of a Sysmex XN-2000 haematology
      analyser. A non-parametric percentile method was used to calculate the reference
      intervals in accordance with CLSI guidelines. Results: The obtained reference
      interval for IPF on the Sysmex XN-2000 was 1.6-9.6% (90% confidence intervals
      (CIs) were 1.5-1.8 and 9.3-11.5, respectively). No significant gender difference
      in IPF reference intervals was observed (P = 0.101). Conclusions: This study
      provides, for the first time, a reference interval for IPF using a Sysmex XN-2000
      in a Spanish population, ranging from 1.6 to 9.6%. These data are needed to
      evaluate platelet production in several conditions such as thrombocytopenia,
      inflammatory states and cardiovascular diseases, as well as for future research.

PMID- 29472804
TI  - Henoch-Schonlein purpura in the third trimester of pregnancy.
AB  - Henoch-Schonlein purpura (HSP) is an IgA-mediated small vessels' vasculitis that
      affects the skin, intestines and kidneys. Pregnancy has been reported as an
      exacerbating factor. We present the case of a 24-year-old primigravida with HSP
      that occurred in the third trimester and lasted up to the end of the successful
      delivery. She had pruritic maculopapular exanthema on her legs. Biopsy of a
      cutaneous lesion was performed for histopathologic features and direct
      immunofluorescence (DIF) for the presence of perivascular IgA deposition.
      Histopathology of the cutaneous lesion confirmed leukocytoclastic vasculitis. A
      DIF examination of the skin lesion confirmed deposits of fibrinogen in the small
      blood vessel walls. Six weeks following delivery, the skin lesions almost
      completely disappeared. Control laboratory findings were normal. This case of HSP
      might have been primarily associated with a preceding respiratory infection but
      this should first be carefully investigated due to a possible severe
      immunological disease in the patient's background requiring special attention
      since nephrotic symptoms may occur.

PMID- 29472805
TI  - Gamma heavy-chain disease accompanied with follicular lymphoma: a case report.
AB  - Heavy chain diseases (HCD) are B-cell lymphoprolipherative disorders
      characterized by the production of monoclonal heavy chains without associated
      light chains. Some cases of gamma-HCD (gamma-HCD) are concurrent with other
      lymphoid neoplasm. The monoclonal component is not always detectable by serum
      electrophoresis, and often an immunofixation procedure is necessary to detect
      this component. Prognosis is variable, and no established guidelines for follow
      up are available. We describe a case of a challenging diagnosis of gamma-HCD due
      to the absence of clinical signs frequently reported in the disease (anaemia and
      palatal oedema among others). Haematological malignancy was the first suspicion
      but bone marrow examination was negative. In addition, the presence of an
      autoimmune bicytopenia and a Klinefelter syndrome complicated the clinical
      context of the patient. A thoracoabdominal computed tomography reported many
      small adenopathies whose pathological and immunohystochemical study revealed a
      follicular lymphoma. Shortly after, serum inmunofixation secondary to an abnormal
      electrophoretic pattern revealed a gamma paraprotein without light chains.
      Eventually, gamma-HCD in association with follicular lymphoma was the final
      diagnosis. This is the first case reporting this association.

PMID- 29472806
TI  - Neutrophil gelatinase-associated lipocalin and acute kidney injury in
      endovascular aneurysm repair or open aortic repair: a pilot study.
AB  - Introduction: Acute kidney injury (AKI) occurs frequently after abdominal aortic
      surgery and there is currently no effective marker able to detect early onset.
      The aim of this study is to evaluate the ability of neutrophil gelatinase
      associated lipocalin (NGAL) to early identify the development of acute renal
      damage in patients undergoing endovascular aneurysm repair (EVAR) or open aortic
      repair (OAR). Materials and methods: Serial samples of blood and urine were
      obtained from 25 patients undergoing both EVAR and OAR. Seven male subjects with
      AKI and 18 subjects with no-AKI (17 males, 1 female) were included in the study.
      We determined concentrations of serum creatinine (sCr) and urinary, serum and
      whole blood NGAL (uNGAL, sNGAL, bNGAL) collected at baseline, and after 4 and 18
      hours. AKI was defined according to the RIFLE criteria (risk, injury, failure,
      loss of kidney function, and end-stage kidney disease): increase by 50% in sCr or
      reduction of at least 25% of estimated glomerular filtration rate (eGFR) from
      baseline. Results: Seven patients developed AKI in the stage Risk. There was no
      significant difference in sNGAL concentrations in the AKI group as compared to no
      AKI group. However, the uNGAL/uCreatinine ratio and bNGAL concentrations were
      significantly higher after 18 hours in the AKI group (no-AKI 1.69 (0.91 - 2.47)
      vs AKI 3.2 (2.08 - 5.92) ng/mg for uNGAL/uCreatinine ratio, P = 0.036; and no-AKI
      83 (59 - 131) vs AKI 164 (126 - 263) ng/mL for bNGAL, P = 0.029). Conclusions:
      Our results suggest that uNGAL, sNGAL and bNGAL, after abdominal aortic surgery,
      are not suitable as early biomarkers of AKI.

PMID- 29472807
TI  - Elevated zinc concentrations in a 5 months old infant: A case report.
AB  - Pre-analytical errors account for the majority of laboratory-associated errors.
      In a 5 months old infant hospitalised with lung dysfunction due to prematurity, a
      routine measurement of zinc revealed an unexpected elevated concentration of 20.2
      umol/L (reference interval 10.0 - 19.0 umol/L) compared to 11.6 umol/L five days
      earlier. Zinc measurement was repeated two days later and had further increased
      to 42.4 umol/L. Of note, there were no clinical signs of the increased zinc
      concentrations. Performance data for the zinc analysis (performed by inductively
      coupled plasma mass spectrometry) was found satisfactory. A thorough review of
      the patient's medication and nutrition supplements revealed no relevant zinc
      content. The blood was obtained through capillary blood sampling, and anything at
      the skin puncture site containing zinc could therefore potentially contribute to
      the elevated zinc results. It was investigated if any ointment containing zinc
      had been applied at the puncture site, which revealed that the mother had applied
      vitamin E ointment containing zinc-oxide at the infant's heel. A capillary sample
      obtained from the opposite heel, where no vitamin E ointment had been applied,
      revealed a zinc concentration of 14.3 umol/L. In conclusion, pre-analytical
      contamination with ointments must be considered in case of unexpected
      measurements from capillary blood.

PMID- 29472808
TI  - Pseudohyperkalemia - Potassium released from cells due to clotting and
      centrifugation - a case report.
AB  - Hyperkalemia is a potentially lethal condition. Pseudohyperkalemia should be
      always excluded before implementing treatment to prevent inappropriate cause of
      hypokalemia - equally a potentially lethal condition. Here we present a case
      report of a 62 year female with chronic myeloproliferative disorder, i.e.
      essential thrombocythemia. The laboratory test results for potassium
      concentration were 6.3 mmol/L, for platelet count 1305 x109/L and for leukocyte
      count 39.8 x109/L. This was due to a temporary drug withdrawal after a surgical
      intervention for gastric bleeding. Potassium concentration in lithium heparin
      plasma collected in a vacuum tube without gel separator and in whole blood
      syringe were 4.6 mmol/L and 3.4 mmol/L, respectively. It means that mechanical
      stress such as centrifugation can contribute to spurious hyperkalemia.?Prior to
      reporting unexpected hyperkalemia result, pseudohyperkalemia should always be
      considered by the laboratory. Such potassium results require investigation in
      case it is pseudohyperkalemia, which may be due to thrombocytosis and
      leukocytosis. In cases where thrombocytosis or leukocytosis exists, an
      interpretative comment indicating these conditions inserted with the results of
      the potassium concentration can increase awareness for more accurate patient care
      decisions.

PMID- 29472809
TI  - The decrease in number of splenic lymphocytes in mice fed Rhodiola kirilowii
      during pregnancy and lactation concerns mainly CD19+ and CD4+ cells.
AB  - In previous work we described the decline in the number of splenocytes of mice
      which during pregnancy and lactation were fed Rhodiola kirilowii. In this work we
      present the size of individual subpopulations of splenic lymphocytes in these
      mice. Experiments were performed on adult inbred female Balb/c mice, 8-9 weeks
      old, 20-22 g b.m., mated with adult males from the same strain. Females, from
      when the copulatory plug was noted up to the 28th day after delivery, were
      supplemented daily with lyophilized aqueous (RKW) or 50% hydro-ethanolic (RKW-A)
      extract (20 mg/kg b.m.) dissolved in distilled water. Then, mice were euthanized,
      spleens dissected, cells counted and the total numbers of CD3+, CD19+, CD4+, CD8+
      and CD335+ splenic lymphocytes were evaluated by cytometry. The number of CD3+
      lymphocytes per 1 g of splenic tissue was higher in RKW-A than in RKW spleens and
      did not differ from the control. The number of CD3+ lymphocytes in RKW spleens
      was lower than in the controls. The number of CD19+ and CD4+ cells was lower in
      both experimental groups than in the controls. The number of CD335+(NK) cells was
      lower in RKW spleens than in the control.

PMID- 29472810
TI  - Concentration of MMP-8 and IL-1beta in gingival crevicular fluid in patients with
      chronic and aggressive periodontitis.
AB  - Modern research confirms the role of inflammatory mediators in the pathomechanism
      of periodontal tissue destruction. The aim of the study was to determine
      concentrations of MMP-8 and IL-1beta in gingival crevicular fluid (GCF) in
      patients with advanced chronic and aggressive periodontitis. The authors measured
      the concentrations of the above inflammatory mediators in gingival crevicular
      fluid of deep pockets (PD >= 6 mm) and shallow pockets (PD 4-5 mm) in 33 patients
      with advanced chronic periodontitis and in 16 patients with aggressive
      periodontitis. The control group consisted of 16 individuals with healthy
      periodontium. In all patients levels of MMP-8 and IL-1beta in GCF were determined
      with the ELISA method. The study showed significantly higher concentrations of
      MMP-8 and IL-1beta in GCF of both deep and shallow pockets in patients with
      periodontitis compared to healthy subjects. No difference in concentrations of
      the tested mediators was observed with reference to diagnosis of aggressive
      periodontitis (AP) or chronic periodontitis (CP).

PMID- 29472811
TI  - The influence of KIR gene presence/absence polymorphisms on the development of
      periodontal disease in smokers and non-smokers.
AB  - Introduction: Periodontal diseases are highly prevalent inflammatory,
      multifactorial diseases. Smoking is one of the most important environmental risk
      factors for the development and severity of periodontal disease. Killer cell
      immunoglobulin-like receptors (KIRs) are members of the immunoglobulin (Ig)
      superfamily and play an essential role in the regulation of NK cell activity,
      allowing natural killer (NK) cells to sense and respond to human leukocyte
      antigen (HLA) class I. The aim of this study was to evaluate the influence of KIR
      gene presence/absence polymorphisms on the development of periodontal disease in
      smokers and non-smokers. Material and methods: This study enrolled 400 Caucasian
      subjects (age range 25-69 years) from the West Pomeranian region of Poland. The
      subjects were categorized into four subgroups (smoking and non-smoking patients
      with periodontal disease; smoking and non-smoking subjects without periodontal
      disease - control subjects). Results: The differences of KIR gene frequencies
      between non-smoking patients and non-smoking control subjects as well as smoking
      patients and control subjects were not statistically significant. In multivariate
      regression analysis advanced age of patients and smoking were independent factors
      associated with increased frequency of periodontal disease. Conclusions: The
      results of this study suggest that the main factor associated with increased risk
      of periodontal disease is smoking, whereas KIR presence/absence polymorphism is
      not a significant factor involved in the pathogenesis of periodontal disease.

PMID- 29472812
TI  - Levels of cytokines in drug hypersensitivity.
AB  - Introduction: Multiple drug intolerance is a serious complication of drug therapy
      and is an issue of allergology. The aim of the study was the investigation of
      cytokine status in patients with drug hypersensitivity and multiple drug
      hypersensitivity. Material and methods: 19 patients with multiple drug
      hypersensitivity, 34 patients with hypersensitivity to one drug, and 35 non
      allergic subjects were involved. Only women were included in the study. A
      multiplex assay of 27 cytokines and chemokines was performed using xMap
      technology (Human Cytokine Panel I by Bio-Rad). Results: Women with drug allergy
      revealed increased IL-2 levels (p < 0.05). In the case of the study of cytokine
      status in patients with multiple drug hypersensitivity, the new data revealed the
      prevalence of pro-inflammatory cytokine status with the participation of
      cytokines IL-17, IL-9, TNF-alpha, IP-10, and MIP-1. Conclusions: Various immune
      response arms Th2, Th17, as well as macrophages were the determining factors in
      the cytokine balance that was found in patients with multiple drug
      hypersensitivity.

PMID- 29472813
TI  - Can mean platelet volume and neutrophil-to-lymphocyte ratio be biomarkers of
      acute exacerbation of bronchiectasis in children?
AB  - Introduction: Bronchiectasis (BE) is a parenchymal lung disease evolving as a
      result of recurrent lung infections and chronic inflammation. Although it has
      been shown in adult studies that mean platelet volume (MPV) and neutrophil-to
      lymphocyte ratio (NLR) can be used as biomarkers of airway inflammation,
      knowledge is limited in the paediatric age group. The aim of our study is to
      investigate the potential of MPV and NLR as biomarkers that may indicate acute
      exacerbations of non-cystic fibrosis BE in children. Material and methods:
      Children with non-cystic fibrosis BE (n = 50), who were followed in the division
      of Paediatric Pulmonology of our hospital between June 2010 and July 2015, were
      involved in the present retrospective cross-sectional study. Haemogram values
      during acute exacerbations and non-exacerbation periods, and a control group were
      compared. Results: In children with bronchiectasis, the average leukocyte count
      (p < 0.001), platelet count (p = 0.018), absolute neutrophil count (p < 0.001),
      and NLR (p < 0.001) were higher, as expected, when compared with the control
      group. NLR values, in the period of acute exacerbation were significantly higher
      than the values of both the non-exacerbation periods (p = 0.02) and the control
      group (p < 0.001). In contrast, MPV values in the period of acute exacerbation
      did not exhibit a significant difference from those of non-exacerbation periods
      (p = 0.530) and the control group (p = 0.103). Conclusions: It was concluded that
      leukocyte count, platelet count, absolute neutrophil count, and NLR can be used
      to show chronic inflammation in BE, but only NLR and absolute neutrophil count
      can be used as biomarkers to show acute exacerbations.

PMID- 29472814
TI  - FcgammaRIIa defunctioning polymorphism in paediatric patients with renal
      allograft.
AB  - Introduction: Fc gamma receptor (FcgammaR) IIa is considered the most widely
      distributed of the three classes of Fc receptors, and it expresses an allelic
      polymorphism. This type of polymorphism may modify the immune response and may be
      an important factor for some diseases. The aim of the study reported herein was
      to evaluate the association between the FcgammaRIIa polymorphism and
      susceptibility to both end-stage renal disease (ESRD) and acute kidney graft
      rejection (AR) in children who have undergone renal transplantation. Material and
      methods: The study evaluated 70 children who had undergone transplantation and 60
      healthy subjects. AR was observed in 25 children. Results: FcgammaRIIa genotypes
      and alleles were significantly different between transplantation patients and the
      control group. The assessment for FcgammaR of the groups in which AR was present
      showed that there was only a risk of having an acute rejection in homozygous
      genotype RR. Conclusions: FcgammaRIIa RR genotype and allele frequency was
      increased in paediatric renal transplant recipients. The present findings showed
      that FcgammaRIIa genotype may be related to ESRD disease susceptibility, and
      FcgammaRIIa polymorphisms seemed to affect AR.

PMID- 29472815
TI  - Angiogenesis modulation by exogenous antioxidants.
AB  - Co-operation of the endogenous and exogenous defense system maintains redox
      homeostasis and is essential for health. The endogenous defense system includes
      enzymatic (e.g. superoxide dismutase, catalase) and non-enzymatic, low molecular
      weight scavengers (e.g. glutathione, ascorbic acid). Pathogenesis of many serious
      diseases (e.g. cancer, ischemic heart disease) includes oxidative stress which
      can disturb angiogenesis, the process of formation of new blood vessels sprouting
      from the existing one. Antioxidants, through reduction of oxidative stress and
      influence on neovascularization, may modulate progress and results of therapy in
      those diseases where such processes play an important role. Herein the impact of
      exogenous antioxidants on angiogenesis and factors modulating this process is
      presented. Most synthetic antioxidants whose activity has been described (namely
      N-acetylcysteine, pentoxifylline, synthetic analogue of curcumin, synthetic
      analogue of epigallocatechin-3 gallate [EGCG], tripertenoids) exert an inhibitory
      effect on neovascularization. A similar effect was also exhibited by several
      natural origin antioxidants (e.g. resveratrol, EGCG), which suggests that their
      application in therapy might normalize excessive angiogenesis. Some natural
      origin antioxidants e.g. purple coneflower and preparations consisting of natural
      antioxidants such as Padma 28 and Immunal forte increase a too low baseline level
      of angiogenesis and decreases a too high level. These preparations exert a
      regulatory effect on and may normalize neovascularization. They can be used in
      the case of diseases associated with too low or too high angiogenesis.

PMID- 29472816
TI  - Disorders noticed during development of pancreatic cancer: potential
      opportunities for early and effective diagnostics and therapy.
AB  - Pancreatic cancer, with a total five-year survival rate below 5%, represents a
      disease with a high level of malignancy. Some of the pancreatic cancer bad
      prognosis factors are nutrition disorders. Malnutrition, neither recognized nor
      properly referred to by the healthcare system, leads to well-documented negative
      health consequences in hospitalized patients including their impaired immunity,
      delayed post-surgery wound healing, a high risk of infectious complications,
      morbidity and mortality. There are numerous factors contributing to the
      development of pancreatic cancer, including telomerases, inflammation,
      angiogenesis, epigenetics and genetics factors, miRNA, pancreatic cancer stem
      cells. On the basis of molecular analyses, it has been established that precursor
      injuries may trigger pancreatic cancer when added to genetic alterations.
      Perhaps, combination of few presently used methods, like signal transduction
      modulated by K-ras, STAT3 activation, HMGB1 releasing, presence of oxidative
      stress and free radicals secretion, genes for proangiogenic growth factors
      activation or tissue-specific miRNA genes expression - will solve the problem of
      inadequate diagnostics.

PMID- 29472817
TI  - Myeloid-derived suppressor cells in ovarian cancer: friend or foe?
AB  - Although previous decades contributed to major progress in targeted therapy of
      many malignancies, the treatment of gynaecological cancers remains a challenging
      task. In the evidence of rising cancer mortality, the search for new methods of
      treatment is a dire need. Exploring the mechanisms of interaction between tumour
      cells and host immune response may allow the introduction of new, effective
      therapies - not as toxic and far more efficient than conventional methods of
      cancer treatment. Epithelial ovarian cancer (EOC) is typically diagnosed at
      advanced stages. Its incidence and mortality rate is high. Powerful diagnostic
      tools for this kind of cancer are still under investigation. Multiple mechanisms
      existing in the ovarian tumour network create a specific immunosuppressive
      microenvironment, in which accumulation of myeloid-derived suppressor cells
      (MDSCs) may be a critical component for diagnosis and treatment. This review
      attempts to verify current knowledge on the role of MDSCs in EOC.

PMID- 29472818
TI  - The role of anti-citrullinated protein antibodies (ACPA) in the pathogenesis of
      rheumatoid arthritis.
AB  - The most specific autoimmunity known for rheumatoid arthritis (RA) is reflected
      by generation of anti-citrullinated protein antibodies (ACPA). Presence of ACPA
      in established RA is associated with disease severity, while generation of ACPA
      at early developmental phases of RA can have a strong predictive value for
      progressing to the full-blown disease. Hence, development of ACPA may be of
      crucial importance to the pathogenesis of RA. Therefore, a lot of effort has been
      put recently to investigate the feature of ACPA at early developmental stages of
      RA (before disease onset) and functional activities of these autoantibodies.
      Results of these studies enlarged the knowledge about the nature of ACPA, which
      is essential for planning the therapeutic or preventive strategies interfering
      with their development and pathogenic functions. In this review we describe
      recent evidence for a role of ACPA in the etiopathogenesis of RA and indicate key
      unresolved issues regarding ACPA biology that need to be clarified in the future.

PMID- 29472819
TI  - Butyrophilins: an important new element of resistance.
AB  - Butyrophilins belonging to the immunoglobulin superfamily are new immune system
      regulators because they are present on lymphocytes, dendritic cells, monocytes,
      macrophages, neutrophils and eosinophils, and they exert a stimulatory and (or)
      inhibitory effect on them. The role of butyrophilins is associated and results
      from their similarity to the regulatory B7 protein family involved in the
      modulation of immune phenomena. Butyrophilins are glycoproteins built of two
      extracellular immunoglobulin domains, stabilized with disulfide bonds: constant
      IgC, and variable IgV and a transmembrane region. Most of these proteins contain
      a conserved domain encoded by a single exon - B30.2, also referred to as PRYSPRY.
      In humans, the family of butyrophilins includes 7 butyrophilin proteins, 5
      butyrophilin-like proteins and the SKINT-like factor. Butyrophilins have been
      also demonstrated to play a role in various infections, e.g. tuberculosis or
      diseases that include sarcoidosis, systemic lupus erythematosus, rheumatoid
      arthritis, genetic metabolic diseases, ulcerative colitis, cancer and kidney
      disease.

PMID- 29472820
TI  - Diagnostic difficulties in a patient with paroxysmal cold haemoglobinuria and
      acute kidney injury.
AB  - Paroxysmal cold haemoglobinuria (PCH) is a form of autoimmune haemolytic anaemia
      (AIHA) characterised by a sudden onset of haemoglobinuria, either spontaneously
      or following exposure to cold. In children, it is commonly seen following a viral
      illness or after immunisation. Diagnosis of PCH is confirmed by a positive Donath
      Landsteiner (DL) test in which biphasic haemolysins are detected. However, in a
      real clinical setting, the serological diagnosis of PCH is not always easy. PCH
      can cause tubular renal injury, which in turn can lead to renal impairment. We
      describe a case of a two-year-old boy who was admitted to the hospital with
      pallor, jaundice, dehydration, and dark urine. Two weeks before admission, the
      child had an upper respiratory tract infection. Laboratory tests showed severe
      anaemia (haemoglobin 4.5g/dl, haematocrit 11.5%, LDH 8525 U/l),
      hyperbilirubinaemia (104 MUmol/l), haemoglobinuria, and acute kidney injury: GFR
      43.9 ml/min/1.73 m2 (grade 2 according to Acute Kidney Injury Network). The
      direct antiglobulin test was positive for C3c and C3d complement components. The
      diagnosis of PCH was confirmed by the presence of biphasic antibodies in a DL
      test on the third day of hospitalisation. The patient received supportive
      treatment.

PMID- 29472821
TI  - Thrombotic thrombocytopenic purpura in the course of systemic lupus erythematosus
      in a 15-year-old girl.
AB  - Systemic lupus erythematosus (SLE) concomitant with thrombotic thrombocytopenic
      purpura (TTP) in children is rarely diagnosed. We report a case of a 15-year-old
      girl with butterfly patch, generalized edema, leg pain, anemia (Hb 74 g/l),
      thrombocytopenia (5 x 109/l), schistocytes in peripheral blood smear, acute
      kidney injury (eGFR 27 ml/min/1.73 m2), proteinuria, and erythrocyturia. The
      direct Coombs test was positive, and warm antibodies (IgG) were detected on red
      blood cells. ANA in titer 1 : 2560, low serum C3 and C4 complement level,
      ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif,
      member 13) activity < 4% and the presence of ADAMTS13 inhibitor were detected. In
      renal biopsy class IVA/V lupus nephritis was diagnosed. Her clinical symptoms
      fulfilled criteria for the diagnosis of SLE and the diagnosis of TTP. She was
      treated with intravenous methylprednisolone and cyclophosphamide 750 mg/1.73
      m2/monthly for six months, followed by oral prednisone with azathioprine,
      chloroquine, and enalapril. The long-term clinical outcome was good. We report a
      case rare in adolescents, TTP related to SLE, which may suggest the need to test
      for ADAMTS13 activity and the presence of ADAMTS13 inhibitor in children with SLE
      and anemia, thrombocytopenia and rapid deterioration of renal function, to make
      the right therapeutic decisions.

PMID- 29472822
TI  - Presence of a single nucleotide polymorphism (RS3758581) in a boy with DRESS
      syndrome.
AB  - Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a rare,
      potentially life-threatening, drug-induced hypersensitivity reaction that
      includes rash, hematologic abnormalities, lymphadenopathy, and internal organ
      involvement. The pathogenesis of DRESS syndrome is partially understood. Various
      medications have been described as the cause of DRESS syndrome. Phenytoin and
      allopurinol are the most commonly reported culprit drugs, although more than 50
      drugs can induce DRESS syndrome. Members of the cytochrome P450 (CYP) superfamily
      are the most commonly involved enzymes in metabolism of drugs such as phenytoin.
      This case report addresses the influence of CYP2C9 genetic polymorphism (a single
      nucleotide polymorphism) on phenytoin drug metabolism, thereby causing DRESS
      syndrome.

PMID- 29472823
TI  - Clinical variability of chromosome 22q11.2 deletion syndrome.
AB  - 22q11.2 deletion syndrome (22q11.2 DS) is a disorder that has multiple symptoms
      and affects various organs and systems. Despite the great variability of clinical
      manifestations, common 22q11.2 DS includes congenital heart defect,
      immunodeficiency, characteristic facial features, palatal defects, developmental
      and/or learning disabilities, and hypocalcaemia. We present the cases of three
      patients with 22q11.2 DS that we have observed. Heart defects were revealed in
      all cases, and tetralogy of Fallot in one of them. Immune system disorders in
      these cases were highly variable and did not correlate with aplasia or hypoplasia
      of the thymus. Cleft palate was diagnosed only in one case. Characteristic facial
      features were presented in all cases but they were not significant and varied
      from subtle to mild. Developmental disability was presented by motor delays in
      two cases. Hypocalcaemia was revealed in one patient, and seizures were absent.
      Only one case completely fit CATCH-22 syndrome (cardiac defects, abnormal facies,
      thymic hypoplasia, cleft palate, and hypocalcaemia caused by22q11.2 deletion).
      The other cases had three out of the five main features, with some other, less
      significant signs also presented. In some cases, even just a few signs should be
      the reason for further examination to exclude 22q11.2 deletion syndrome.
      Currently, immunological disorders are not a significant determinant in the
      diagnosis of this syndrome, and timely correction of heart defects can reduce the
      number of recurrent respiratory infections. A multidisciplinary approach to the
      management of these patients and providing timely, complex medical care will
      prevent serious complications.

PMID- 29472824
TI  - Active Surveillance Use Among a Low-risk Prostate Cancer Population in a Large US
      Payer System: 17-Gene Genomic Prostate Score Versus Other Risk Stratification
      Methods.
AB  - Many men with low-risk prostate cancer (PCa) receive definitive treatment despite
      recommendations that have been informed by two large, randomized trials
      encouraging active surveillance (AS). We conducted a retrospective cohort study
      using the OptumTM Research Database (Eden Prairie, MN) of electronic health
      records and administrative claims data to assess AS use for patients tested with
      a 17-gene Genomic Prostate ScoreTM (GPS; Genomic Health, Redwood City, CA) assay
      and/or prostate magnetic resonance imaging (MRI). De-identified records were
      extracted on health plan members enrolled from June 2013 to June 2016 who had >=1
      record of PCa (n 5 291,876). Inclusion criteria included age >=18 years, new
      diagnosis, American Urological Association low-risk PCa (stage T1-T2a, prostate
      specific antigen <=10 ng/mL, Gleason score 5 6), and clinical activity for at
      least 12 months before and after diagnosis. Data included baseline
      characteristics, use of GPS testing and/or MRI, and definitive procedures. GPS or
      MRI testing was performed in 17% of men (GPS, n 5 375, 4%; MRI, n 5 1174, 13%).
      AS use varied from a low of 43% for men who only underwent MRI to 89% for
      GPStested men who did not undergo MRI (P <.001). At 6-month follow-up, AS use was
      31.0% higher (95% CI, 27.6%-34.5%; P <.001) for men receiving the GPS test only
      versus men who did not undergo GPS testing or MRI; the difference was 30.5% at 12
      month follow-up. In a large US payer system, the GPS assay was associated with
      significantly higher AS use at 6 and 12 months compared with men who had MRI
      only, or no GPS or MRI testing.

PMID- 29472825
TI  - A Head-to-Head Comparative Phase II Study of Standard Urine Culture and
      Sensitivity Versus DNA Next-generation Sequencing Testing for Urinary Tract
      Infections.
AB  - Many studies have discussed clinical practice guidelines for the treatment of
      cystitis and pyelonephritis. Treatment of uncomplicated urinary tract infections
      (UTIs) can be based on empiric antibiotic therapy. For complicated or recurrent
      UTIs, therapy can be based on laboratory-controlled culture and sensitivity (C&S)
      reports. The diagnosis of UTI by clinical criteria alone has an error rate of up
      to 33%. In addition, positive laboratory culture results do not always indicate a
      diagnosis of UTI. Comparison of urine in a conventional culture model versus DNA
      next-generation sequencing (NGS) to accurately identify and provide information
      on resistance factors (mobile genetic elements) is warranted. Our study was a
      head-to-head comparative phase II study of standard urine C&S versus DNA NGS
      testing for the diagnosis and treatment efficacy in patients with symptoms of
      acute cystitis based on short-term outcomes.

PMID- 29472827
TI  - Are You Developing an ABC: Advanced Bladder Cancer Clinic?

PMID- 29472828
TI  - Successfully Integrating Radium Ra 223 Dichloride Injection Into a Urology
      Practice.

PMID- 29472826
TI  - The Use of Biomarkers in Prostate Cancer Screening and Treatment.
AB  - Prostate cancer screening and diagnosis has been guided by prostate-specific
      antigen levels for the past 25 years, but with the most recent US Preventive
      Services Task Force screening recommendations, as well as concerns regarding
      overdiagnosis and overtreatment, a new wave of prostate cancer biomarkers has
      recently emerged. These assays allow the testing of urine, serum, or prostate
      tissue for molecular signs of prostate cancer, and provide information regarding
      both diagnosis and prognosis. In this review, we discuss 12 commercially
      available biomarker assays approved for the diagnosis and treatment of prostate
      cancer. The results of clinical validation studies and clinical decision-making
      studies are presented. This information is designed to assist urologists in
      making clinical decisions with respect to ordering and interpreting these tests
      for different patients. There are numerous fluid and biopsy-based genomic tests
      available for prostate cancer patients that provide the physician and patient
      with different information about risk of future disease and treatment outcomes.
      It is important that providers be able to recommend the appropriate test for each
      individual patient; this decision is based on tissue availability and prognostic
      information desired. Future studies will continue to emphasize the important role
      of genomic biomarkers in making individualized treatment decisions for prostate
      cancer patients.

PMID- 29472829
TI  - Prostate Cancer Academy 2017 Summaries.

PMID- 29472830
TI  - Ureteropelvic Junction Obstruction in Adults.

PMID- 29472831
TI  - Diagnosis and Treatment of Persistent Genital Arousal Disorder.

PMID- 29472832
TI  - Irreversible Electroporation for Prostate Cancer as Salvage Treatment Following
      Prior Radiation and Cryotherapy.
AB  - Salvage treatment options after localized primary treatment failure of prostate
      cancer are limited and associated with risk for serious complications. We report
      on the management details of a 57-year-old African American man treated with
      partial-gland ablation using irreversible electroporation following local
      recurrence after brachytherapy and prior salvage cryoablation. Therapeutic and
      functional outcomes were assessed by conventional means, including serum prostate
      specific antigen values and prostate biopsy results.

PMID- 29472833
TI  - Cycling Trauma as a Cause of Arterial Priapism in Children and Teenagers.
AB  - Bicycle riding has multiple beneficial cardiovascular effects; however, it is a
      well-documented source of significant urologic injuries. Priapism is a rare
      condition in children, and occurs primarily because of congenital hematologic
      diseases or adverse drug reactions. A pediatric clinical case and literature
      review of a high-flow priapism secondary to cycling trauma is described here to
      highlight their etiopathologic correlation. Bicycle riding trauma is a rare but
      possible cause of high-flow priapism in children, and a high index of suspicion
      should ensure appropriate management.

PMID- 29472834
TI  - Real world data in health technology assessments in kidney transplants in
      Germany: use of routinely collected data to address epidemiologic questions in
      kidney transplants in the AMNOG process in Germany.
AB  - Introduction: It is discussed whether real world data can be used in health
      technology assessment. Following it is of interest whether routinely collected
      data for quality assurance (QA) in the hospital sector is feasible to address
      epidemiologic questions in kidney transplantation in the AMNOG process in
      Germany. Objectives: To investigate the proportion of kidney transplants
      classified as from so-called standard criteria donors (SCD) and from expanded
      criteria donors (ECD) in Germany and to study the age distribution. Methods:
      After granted use by the Federal Joint Committee (G-BA), the data analysis was
      carried out by the AQUA institute, and a SPSS code was developed. Special
      challenge was the complex definition of SCD/ECD criteria that, in addition to
      donor age, takes into account combinations of donor diagnoses, creatinine, and
      cold ischemia time. Results: Age analyses could be performed in all patients.
      Median age of the adult transplant recipients in Germany was 54 years in 2012 as
      well as in 2013, range 18-85 and 18-82 years and a mean (SD) of 53 (14) and 52
      (14) years, respectively. 63.5% (2012) and 62.5% (2013) of recipients were male.
      Classification in SCD/ECD transplants could be performed for 2,083 of 2,461
      patients (85%; 2012) and for 1,795 of 2,079 patients (86%; 2013). Of all
      classifiable transplants 61.4% (2012) and 66.5% (2013) were SCD transplants.
      Total project time from the request to results was <6 months. Conclusions: The
      use of data routinely collected for QA in the hospital sector is feasible to
      address epidemiologic questions in kidney transplantation in the AMNOG process in
      Germany, which is basically following the systematic of an HTA process. All
      patients with kidney transplants are represented thus avoiding sampling error.
      Limitations include the availability of all necessary data in the QA data set.
      Within <6 months' time with reasonable resources it was possible to meet
      timelines. The analyses were accepted by the authorities.

PMID- 29472835
TI  - Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal
      Model of Inhalant Abuse.
AB  - Thinners are highly toxic chemicals widely employed as organic solvents in
      industrial and domestic use. They have psychoactive properties when inhaled, and
      their chronic abuse as inhalants is associated with severe long-term health
      effects, including brain damage and cognitive-behavioral alterations. Yet, the
      sites and mechanisms of action of these compounds on the brain are far from being
      fully understood. Here, we investigated the consequences of paint thinner
      inhalation in adult male mice. Depression-like behaviors and an anxiolytic effect
      were found following repeated exposure in chronic treatments lasting 12 weeks.
      Both subchronic (6 weeks) and chronic treatments impaired learning and memory
      functions, while no changes were observed after acute treatment. To investigate
      possible molecular/structural alterations underlying such behavioral changes, we
      focused on the hippocampus. Notably, prolonged, but not acute thinner inhalation
      strongly affected adult neurogenesis in the dentate gyrus (DG), reducing
      progenitor cell proliferation after chronic treatments and impairing the survival
      of newborn neurons following both chronic and subchronic treatments. Furthermore,
      a down-regulation in the expression of BDNF and NMDA receptor subunits as well as
      a reduction in CREB expression/phosphorylation were found in the hippocampi of
      chronically treated mice. Our findings demonstrate for the first time significant
      structural and molecular changes in the adult hippocampus after prolonged paint
      thinner inhalation, indicating reduced hippocampal neuroplasticity and strongly
      supporting its implication in the behavioral dysfunctions associated to inhalant
      abuse.

PMID- 29472836
TI  - Group-Level EEG-Processing Pipeline for Flexible Single Trial-Based Analyses
      Including Linear Mixed Models.
AB  - Here we present an application of an EEG processing pipeline customizing EEGLAB
      and FieldTrip functions, specifically optimized to flexibly analyze EEG data
      based on single trial information. The key component of our approach is to create
      a comprehensive 3-D EEG data structure including all trials and all participants
      maintaining the original order of recording. This allows straightforward access
      to subsets of the data based on any information available in a behavioral data
      structure matched with the EEG data (experimental conditions, but also
      performance indicators, such accuracy or RTs of single trials). In the present
      study we exploit this structure to compute linear mixed models (LMMs, using lmer
      in R) including random intercepts and slopes for items. This information can
      easily be read out from the matched behavioral data, whereas it might not be
      accessible in traditional ERP approaches without substantial effort. We further
      provide easily adaptable scripts for performing cluster-based permutation tests
      (as implemented in FieldTrip), as a more robust alternative to traditional
      omnibus ANOVAs. Our approach is particularly advantageous for data with
      parametric within-subject covariates (e.g., performance) and/or multiple complex
      stimuli (such as words, faces or objects) that vary in features affecting
      cognitive processes and ERPs (such as word frequency, salience or familiarity),
      which are sometimes hard to control experimentally or might themselves constitute
      variables of interest. The present dataset was recorded from 40 participants who
      performed a visual search task on previously unfamiliar objects, presented either
      visually intact or blurred. MATLAB as well as R scripts are provided that can be
      adapted to different datasets.

PMID- 29472837
TI  - Spike-Timing Dependent Plasticity in Unipolar Silicon Oxide RRAM Devices.
AB  - Resistance switching, or Resistive RAM (RRAM) devices show considerable potential
      for application in hardware spiking neural networks (neuro-inspired computing) by
      mimicking some of the behavior of biological synapses, and hence enabling non-von
      Neumann computer architectures. Spike-timing dependent plasticity (STDP) is one
      such behavior, and one example of several classes of plasticity that are being
      examined with the aim of finding suitable algorithms for application in many
      computing tasks such as coincidence detection, classification and image
      recognition. In previous work we have demonstrated that the neuromorphic
      capabilities of silicon-rich silicon oxide (SiOx) resistance switching devices
      extend beyond plasticity to include thresholding, spiking, and integration. We
      previously demonstrated such behaviors in devices operated in the unipolar mode,
      opening up the question of whether we could add plasticity to the list of
      features exhibited by our devices. Here we demonstrate clear STDP in unipolar
      devices. Significantly, we show that the response of our devices is broadly
      similar to that of biological synapses. This work further reinforces the
      potential of simple two-terminal RRAM devices to mimic neuronal functionality in
      hardware spiking neural networks.

PMID- 29472838
TI  - Cancer Imprints an Increased PARP-1 and p53-Dependent Resistance to Oxidative
      Stress on Lymphocytes of Patients That Later Develop Alzheimer's Disease.
AB  - We have proposed that a common biological mechanism deregulated in opposite
      directions might explain the inverse epidemiological association observed between
      Alzheimer's disease (AD) and cancer. Accordingly, we showed that lymphocytes from
      AD patients have an increased susceptibility, whereas those from survivors of a
      skin cancer, an increased resistance to oxidative death induced by hydrogen
      peroxide (H2O2), compared to healthy controls (HC). We investigated the
      susceptibility to H2O2-induced death of lymphocytes in survivors of any type of
      cancer and in cancer survivors who later developed AD (Ca&AD). We also explored
      the involvement of Poly [ADP-ribose] polymerase-1 (PARP-1) and p53 pathways in
      the process, since both are involved in the increased susceptibility to death of
      AD lymphocytes. Lymphocytes from 11 cancer and 13 Ca&AD patients, and 12 HC were
      submitted to increasing concentrations of H2O2 for 20 h. Cell death was
      determined by flow cytometry, in the presence or absence of PARP-1 inhibition (3
      aminobenzamide, 3-ABA), or p53 inhibition (pifithrin-alpha) or stabilization (Nut
      3). PARP-1 and p53 mRNA levels were determined by Real-Time PCR. Lymphocytes from
      cancer and Ca&AD patients showed increased survival compared to HC, without
      differences between them, opposite to the increased susceptibility to death
      previously shown in AD. PARP-1 inhibition provided marked protection from H2O2
      induced death in the two groups of patients, significantly greater than in HC.
      Pharmacological inhibition of p53 increased lymphocyte survival in Ca&AD
      patients, contrary to the effect previously reported in HC and AD. PARP-1 and p53
      mRNA levels were elevated in Ca&AD lymphocytes compared with controls. In all,
      these results show that cancer imprints an increased resistance to H2O2-induced
      death in lymphocytes that persists after AD development, and is dependent on both
      PARP-1 and p53. p53 inhibition showed a differential role in cancer and Ca&AD
      compared to HC and AD lymphocytes, that could explain the inverse susceptibility
      to oxidative death in cancer and AD. These results are in agreement with the
      hypothesis of a common biological mechanism in AD and cancer. The similar cell
      death susceptibility and cell death pattern observed in cancer and Ca&AD
      lymphocytes suggests that cancer history leaves long term effects on lymphocyte
      cell death susceptibility.

PMID- 29472839
TI  - Ketamine Modulates Zic5 Expression via the Notch Signaling Pathway in Neural
      Crest Induction.
AB  - Ketamine is a potent dissociative anesthetic and the most commonly used illicit
      drug. Many addicts are women at childbearing age. Although ketamine has been
      extensively studied as a clinical anesthetic, its effects on embryonic
      development are poorly understood. Here, we applied the Xenopus model to study
      the effects of ketamine on development. We found that exposure to ketamine from
      pre-gastrulation (stage 7) to early neural plate (stage 13.5) resulted in
      disruption of neural crest (NC) derivatives. Ketamine exposure did not affect
      mesoderm development as indicated by the normal expression of Chordin, Xbra,
      Wnt8, and Fgf8. However, ketamine treatment significantly inhibited Zic5 and Slug
      expression at early neural plate stage. Overexpression of Zic5 rescued ketamine
      induced Slug inhibition, suggesting the blockage of NC induction was mediated by
      Zic5. Furthermore, we found Notch signaling was altered by ketamine. Ketamine
      inhibited the expression of Notch targeted genes including Hes5.2a, Hes5.2b, and
      ESR1 and ketamine-treated embryos exhibited Notch-deficient somite phenotypes. A
      15 bp core binding element upstream of Zic5 was induced by Notch signaling and
      caused transcriptional activation. These results demonstrated that Zic5 works as
      a downstream target gene of Notch signaling in Xenopus NC induction. Our study
      provides a novel teratogenic mechanism whereby ketamine disrupts NC induction via
      targeting a Notch-Zic5 signaling pathway.

PMID- 29472840
TI  - Prenatal Immune Challenge in Mice Leads to Partly Sex-Dependent Behavioral,
      Microglial, and Molecular Abnormalities Associated with Schizophrenia.
AB  - Epidemiological studies revealed that environmental factors comprising prenatal
      infection are strongly linked to risk for later development of neuropsychiatric
      disorders such as schizophrenia. Considering strong sex differences in
      schizophrenia and its increased prevalence in males, we designed a methodological
      approach to investigate possible sex differences in pathophysiological
      mechanisms. Prenatal immune challenge was modeled by systemic administration of
      the viral mimic polyinosinic-polycytidylic acid (Poly I:C) to C57BL/6 mice at
      embryonic day 9.5. The consequences on behavior, gene expression, and microglia
      brain immune cells that are critical for normal development-were characterized in
      male vs. female offspring at adulthood. The cerebral cortex, hippocampus, and
      cerebellum, regions where structural and functional alterations were mainly
      described in schizophrenia patients, were selected for cellular and molecular
      analyses. Confocal and electron microscopy revealed most pronounced differences
      in microglial distribution, arborization, cellular stress, and synaptic
      interactions in the hippocampus of male vs. female offspring exposed to Poly I:C.
      Sex differences in microglia were also measured under both steady-state and Poly
      I:C conditions. These microglial alterations were accompanied by behavioral
      impairment, affecting for instance sensorimotor gating, in males. Consistent with
      these results, increased expression of genes related to inflammation was measured
      in cerebral cortex and hippocampus of males challenged with Poly I:C. Overall,
      these findings suggest that schizophrenia's higher incidence in males might be
      associated, among other mechanisms, with an increased microglial reactivity to
      prenatal immune challenges, hence determining disease outcomes into adulthood.

PMID- 29472841
TI  - The Absence of Sensory Axon Bifurcation Affects Nociception and Termination
      Fields of Afferents in the Spinal Cord.
AB  - A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl
      cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the
      bifurcation of sensory axons upon entering the spinal cord during embryonic
      development. However, the impact of axon bifurcation on sensory processing in
      adulthood remains poorly understood. To investigate the functional consequences
      of impaired axon bifurcation during adult stages we generated conditional mouse
      mutants of Npr2 and cGKI (Npr2fl/fl;Wnt1Cre and cGKIKO/fl;Wnt1Cre ) that lack
      sensory axon bifurcation in the absence of additional phenotypes observed in the
      global knockout mice. Cholera toxin labeling in digits of the hind paw
      demonstrated an altered shape of sensory neuron termination fields in the spinal
      cord of conditional Npr2 mouse mutants. Behavioral testing of both sexes
      indicated that noxious heat sensation and nociception induced by chemical
      irritants are impaired in the mutants, whereas responses to cold sensation,
      mechanical stimulation, and motor coordination are not affected. Recordings from
      C-fiber nociceptors in the hind limb skin showed that Npr2 function was not
      required to maintain normal heat sensitivity of peripheral nociceptors. Thus, the
      altered behavioral responses to noxious heat found in Npr2fl/fl;Wnt1Cre mice is
      not due to an impaired C-fiber function. Overall, these data point to a critical
      role of axonal bifurcation for the processing of pain induced by heat or chemical
      stimuli.

PMID- 29472842
TI  - Accumulation of Cav3.2 T-type Calcium Channels in the Uninjured Sural Nerve
      Contributes to Neuropathic Pain in Rats with Spared Nerve Injury.
AB  - Injuries to peripheral nerve fibers induce neuropathic pain. But the involvement
      of adjacent uninjured fibers to pain is not fully understood. The present study
      aims to investigate the possible contribution of Cav3.2 T-type calcium channels
      in uninjured afferent nerve fibers to neuropathic pain in rats with spared nerve
      injury (SNI). Abeta-, Adelta- and C-fibers of the uninjured sural nerve were
      sensitized revealed by in vivo single-unit recording, which were accompanied by
      accumulation of Cav3.2 T-type calcium channel proteins shown by Western blotting.
      Application of mibefradil, a T-type calcium channel blocker, to sural nerve
      receptive fields increased mechanical thresholds of Abeta-, Adelta- and C-fibers,
      confirming the functional involvement of accumulated channels in the sural nerve
      in SNI rats. Finally, perineural application of mibefradil or TTA-P2 to the
      uninjured sural nerve alleviated mechanical allodynia in SNI rats. These results
      suggest that axonal accumulation of Cav3.2 T-type calcium channels plays an
      important role in the uninjured sural nerve sensitization and contributes to
      neuropathic pain.

PMID- 29472843
TI  - A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after
      Injury.
AB  - Injury to the adult central nervous systems (CNS) can result in severe long-term
      disability because damaged CNS connections fail to regenerate after trauma.
      Identification of regulators that enhance the intrinsic growth capacity of
      severed axons is a first step to restore function. Here, we conducted a gain-of
      function genetic screen in Drosophila to identify strong inducers of axonal
      growth after injury. We focus on a novel axis the Down Syndrome Cell Adhesion
      Molecule (Dscam1), the de-ubiquitinating enzyme Fat Facets (Faf)/Usp9x and the
      Jun N-Terminal Kinase (JNK) pathway transcription factor Kayak (Kay)/Fos. Genetic
      and biochemical analyses link these genes in a common signaling pathway whereby
      Faf stabilizes Dscam1 protein levels, by acting on the 3'-UTR of its mRNA, and
      Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of
      Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities,
      suggesting a conserved mechanism.

PMID- 29472845
TI  - Editorial: Metastable Dynamics of Neural Ensembles.

PMID- 29472844
TI  - F-spondin Is Essential for Maintaining Circadian Rhythms.
AB  - The suprachiasmatic nucleus (SCN) is the master pacemaker that drives circadian
      behaviors. SCN neurons have intrinsic, self-sustained rhythmicity that is
      governed by transcription-translation feedback loops. Intrinsic rhythms within
      the SCN do not match the day-night cycle and are therefore entrained by light
      derived cues. Such cues are transmitted to the SCN by a class of intrinsically
      photosensitive retinal ganglion cells (ipRGCs). In the present study, we sought
      to identify how axons from ipRGCs target the SCN. While none of the potential
      targeting cues identified appeared necessary for retinohypothalamic innervation,
      we unexpectedly identified a novel role for the extracellular matrix protein F
      spondin in circadian behavior. In the absence of F-spondin, mice lost their
      ability to maintain typical intrinsic rhythmicity. Moreover, F-spondin loss
      results in the displacement of vasoactive intestinal peptide (VIP)-expressing
      neurons, a class of neurons that are essential for maintaining rhythmicity among
      SCN neurons. Thus, this study highlights a novel role for F-spondin in
      maintaining circadian rhythms.

PMID- 29472846
TI  - Risk Preferences and Predictions about Others: No Association with 2D:4D Ratio.
AB  - Prenatal androgen exposure affects the brain development of the fetus which may
      facilitate certain behaviors and decision patterns in the later life. The ratio
      between the lengths of second and the fourth fingers (2D:4D) is a negative
      biomarker of the ratio between prenatal androgen and estrogen exposure and men
      typically have lower ratios than women. In line with the typical findings
      suggesting that women are more risk averse than men, several studies have also
      shown negative relationships between 2D:4D and risk taking although the evidence
      is not conclusive. Previous studies have also reported that both men and women
      believe women are more risk averse than men. In the current study, we re-test the
      relationship between 2D:4D and risk preferences in a German student sample and
      also investigate whether the 2D:4D ratio is associated with people's perceptions
      about others' risk preferences. Following an incentivized risk elicitation task,
      we asked all participants their predictions about (i) others' responses (without
      sex specification), (ii) men's responses, and (iii) women's responses; then
      measured their 2D:4D ratios. In line with the previous findings, female
      participants in our sample were more risk averse. While both men and women
      underestimated other participants' (non sex-specific) and women's risky decisions
      on average, their predictions about men were accurate. We also found evidence for
      the false consensus effect, as risky choices are positively correlated with
      predictions about other participants' risky choices. The 2D:4D ratio was not
      directly associated either with risk preferences or the predictions of other
      participants' choices. An unexpected finding was that women with mid-range levels
      of 2D:4D estimated significantly larger sex differences in participants'
      decisions. This finding needs further testing in future studies.

PMID- 29472847
TI  - Balance Training Reduces Brain Activity during Motor Simulation of a Challenging
      Balance Task in Older Adults: An fMRI Study.
AB  - Aging is associated with a shift from an automatic to a more cortical postural
      control strategy, which goes along with deteriorations in postural stability.
      Although balance training has been shown to effectively counteract these
      behavioral deteriorations, little is known about the effect of balance training
      on brain activity during postural tasks in older adults. We, therefore, assessed
      postural stability and brain activity using fMRI during motor imagery alone (MI)
      and in combination with action observation (AO; i.e., AO+MI) of a challenging
      balance task in older adults before and after 5 weeks of balance training.
      Results showed a nonsignificant trend toward improvements in postural stability
      after balance training, accompanied by reductions in brain activity during AO+MI
      of the balance task in areas relevant for postural control, which have been shown
      to be over-activated in older adults during (simulation of) motor performance,
      including motor, premotor, and multisensory vestibular areas. This suggests that
      balance training may reverse the age-related cortical over-activations and lead
      to changes in the control of upright posture toward the one observed in young
      adults.

PMID- 29472848
TI  - Spike Train Similarity Space (SSIMS) Method Detects Effects of Obstacle Proximity
      and Experience on Temporal Patterning of Bat Biosonar.
AB  - Bats emit biosonar pulses in complex temporal patterns that change to accommodate
      dynamic surroundings. Efforts to quantify these patterns have included analyses
      of inter-pulse intervals, sonar sound groups, and changes in individual signal
      parameters such as duration or frequency. Here, the similarity in temporal
      structure between trains of biosonar pulses is assessed. The spike train
      similarity space (SSIMS) algorithm, originally designed for neural activity
      pattern analysis, was applied to determine which features of the environment
      influence temporal patterning of pulses emitted by flying big brown bats,
      Eptesicus fuscus. In these laboratory experiments, bats flew down a flight
      corridor through an obstacle array. The corridor varied in width (100, 70, or 40
      cm) and shape (straight or curved). Using a relational point-process framework,
      SSIMS was able to discriminate between echolocation call sequences recorded from
      flights in each of the corridor widths. SSIMS was also able to tell the
      difference between pulse trains recorded during flights where corridor shape
      through the obstacle array matched the previous trials (fixed, or expected) as
      opposed to those recorded from flights with randomized corridor shape (variable,
      or unexpected), but only for the flight path shape in which the bats had previous
      training. The results show that experience influences the temporal patterns with
      which bats emit their echolocation calls. It is demonstrated that obstacle
      proximity to the bat affects call patterns more dramatically than flight path
      shape.

PMID- 29472849
TI  - EEG-Based Brain-Computer Interfaces for Communication and Rehabilitation of
      People with Motor Impairment: A Novel Approach of the 21 st Century.
AB  - People with severe neurological impairments face many challenges in sensorimotor
      functions and communication with the environment; therefore they have increased
      demand for advanced, adaptive and personalized rehabilitation. During the last
      several decades, numerous studies have developed brain-computer interfaces (BCIs)
      with the goals ranging from providing means of communication to functional
      rehabilitation. Here we review the research on non-invasive,
      electroencephalography (EEG)-based BCI systems for communication and
      rehabilitation. We focus on the approaches intended to help severely paralyzed
      and locked-in patients regain communication using three different BCI modalities:
      slow cortical potentials, sensorimotor rhythms and P300 potentials, as
      operational mechanisms. We also review BCI systems for restoration of motor
      function in patients with spinal cord injury and chronic stroke. We discuss the
      advantages and limitations of these approaches and the challenges that need to be
      addressed in the future.

PMID- 29472850
TI  - Slow Is Also Fast: Feedback Delay Affects Anxiety and Outcome Evaluation.
AB  - Performance-related feedback plays an important role in improving human being's
      adaptive behavior. Using event-related potentials (ERPs), previous studies have
      associated a particular component, i.e., reward positivity (RewP), with outcome
      evaluation processing and found that this component was affected by waiting time
      before outcome evaluation. Prior research has also suggested that anxious
      individuals are more prone to detecting threats and susceptible to negative
      emotions, and show different patterns of brain activity in outcome evaluation. It
      is quite common that a decision-maker cannot receive feedback immediately;
      however, few studies have focused on the processing of delayed feedback,
      especially in subjects who exhibit trait anxiety. In this study, we recruited two
      groups of subjects with different trait anxiety levels and recorded ERPs when
      they conducted a time-estimation task with short (0.6-1 s) or long delayed (4-5
      s) feedback. The ERP results during the cue phase showed that long waiting cues
      elicited more negative-going feedback-related negativity (FRN)-like component
      than short waiting cues in the high trait anxiety (HTA) group. More importantly,
      the two groups showed different patterns of ERP in the feedback condition. In the
      low trait anxiety (LTA) group, more positive-going RewP was found in the short
      delayed than in the long-delayed condition. In contrast, no difference was found
      in the HTA group. This pattern may reflect the hyperactivity of the reward
      systems of HTA individuals in uncertain environments (e.g., the long-delay
      condition) compared with LTA individuals. Our results provide a direction for
      future research on the neural mechanisms of reinforcement learning and anxiety.

PMID- 29472851
TI  - Self-Active Relaxation Therapy (SART) and Self-Regulation: A Comprehensive Review
      and Comparison of the Japanese Body Movement Approach.
AB  - Relaxation programs are known for their versatility, cost-effectiveness, and
      ability to help people obtain skills to regulate their mental states and promote
      and maintain health. Self-Active Relaxation Therapy (SART) is a body-oriented
      approach to psychological rehabilitation that grew out of the suite of movement
      tasks developed in the Japanese psychotherapy known as Dohsa-hou, or the body
      movement method. The program for SART is designed to stretch, twist, and release
      areas of the upper, lower, and whole body through a set of movements which are
      guided by the practitioner and performed "self-actively" by the client to empower
      them to learn to recognize points of tension in the body and act on their own to
      achieve a relaxed state. Numerous studies have showed that SART is associated
      with reduced negative mood states and enhanced body awareness. A short version of
      SART has been investigated as a psychological support salon activity for the
      elderly, mothers raising children, special needs students, and children adapting
      to school. The full program has also been applied in clinical settings to address
      or supplement treatments for psychological and developmental conditions, and
      longitudinally employed in community contexts to assist residents facing long
      term disaster recovery circumstances in Japan. This paper reviews the research
      and applications of SART as a bodymind approach by critically examining evidence
      and research gaps for future studies, comparing it with techniques established in
      the literature, and positing a self-regulatory framework for SART as a tool to
      become aware of bodily states, regulate mood, and manage stress through the
      deliberate practice of relaxation.

PMID- 29472852
TI  - It Is Not Just in Faces! Processing of Emotion and Intention from Biological
      Motion in Psychiatric Disorders.
AB  - Social neuroscience offers a wide range of techniques that may be applied to
      study the social cognitive deficits that may underlie reduced social functioning
      a common feature across many psychiatric disorders. At the same time, a
      significant proportion of research in this area has been conducted using
      paradigms that utilize static displays of faces or eyes. The use of point-light
      displays (PLDs) offers a viable alternative for studying recognition of emotion
      or intention inference while minimizing the amount of information presented to
      participants. This mini-review aims to summarize studies that have used PLD to
      study emotion and intention processing in schizophrenia (SCZ), affective
      disorders, anxiety and personality disorders, eating disorders and
      neurodegenerative disorders. Two main conclusions can be drawn from the reviewed
      studies: first, the social cognitive problems found in most of the psychiatric
      samples using PLD were of smaller magnitude than those found in studies
      presenting social information using faces or voices. Second, even though the
      information presented in PLDs is extremely limited, presentation of these types
      of stimuli is sufficient to elicit the disorder-specific, social cognitive biases
      (e.g., mood-congruent bias in depression, increased threat perception in anxious
      individuals, aberrant body size perception in eating disorders) documented using
      other methodologies. Taken together, these findings suggest that point-light
      stimuli may be a useful method of studying social information processing in
      psychiatry. At the same time, some limitations of using this methodology are also
      outlined.

PMID- 29472853
TI  - Relevance of Phosphorylation and Truncation of Tau to the Etiopathogenesis of
      Alzheimer's Disease.
AB  - Microtubule (MT) associated protein tau is abnormally hyperphosphorylated and
      aggregated into paired helical filaments (PHFs), which manifest as
      neurofibrillary tangles (NFTs) in the brains of individuals with Alzheimer's
      disease (AD) and related tauopathies. Hyperphosphorylation and truncation of tau
      have been linked to the progression of the disease. However, the nature of
      phosphorylation and truncation of tau in AD brain are not very clear. In the
      present study we investigated the association of phosphorylation and truncation
      with high-molecular weight oligomers of tau (HMW-tau) in post-mortem AD brain by
      western blots. We found that tau from AD brain appears as a smear from low
      molecular weight (LMW) to HMW tau species in western blots developed with pan-tau
      antibodies. Similar level of LMW-tau was found in AD and control brains, whereas
      HMW-tau was found in AD brain only. HMW-tau was hyperphosphorylated at multiple
      sites and not unphosphorylated at Ser46 or Ser198/199/202. HMW-tau was weakly
      labeled by tau antibodies 43D against a.a. 6-18 and HT7 against a.a. 159-163 of
      tau, whereas, the C-terminal antibodies, tau46 and tau46.1, strongly labeled HMW
      tau. The ratio of HMW-tau/LMW-tau detected by tau antibodies increased as the
      epitope of the tau antibodies ranges from N-terminal to C-terminal. The level of
      tau truncated at Asp421 was increased in AD brain, but was poorly associated with
      the HMW-tau. These findings suggest that tau pathogenesis involves both
      hyperphosphorylation and dominantly N-terminal truncation of tau in AD.

PMID- 29472854
TI  - Altered Connectivity of the Anterior Cingulate and the Posterior Superior
      Temporal Gyrus in a Longitudinal Study of Later-life Depression.
AB  - Patients with later-life depression (LLD) show abnormal gray matter (GM) volume,
      white matter (WM) integrity and functional connectivity in the anterior cingulate
      cortex (ACC) and posterior superior temporal gyrus (pSTG), but it remains unclear
      whether these abnormalities persist over time. We examined whether structural and
      functional abnormalities in these two regions are present within the same
      subjects during depressed vs. remitted phases. Sixteen patients with LLD and 30
      healthy subjects were studied over a period of 1.5 years. Brain images obtained
      with a 3-Tesla magnetic resonance imaging (MRI) system were analyzed by voxel
      based morphometry of the GM volume, and diffusion tensor imaging (DTI) and
      resting-state functional MRI were used to assess ACC-pSTG connectivity. Patients
      with LLD in the depressed and remitted phases showed significantly smaller GM
      volume in the left ACC and left pSTG than healthy subjects. Both patients with
      LLD in the depressed and remitted phases had significantly higher diffusivities
      in the WM tract of the left ACC-pSTG than healthy subjects. Remitted patients
      with LLD showed lower functional ACC-pSTG connectivity compared to healthy
      subjects. No difference was found in the two regions between depressed and
      remitted patients in GM volume, structural or functional connectivity. Functional
      ACC-pSTG connectivity was positively correlated with lower global function during
      remission. Our preliminary data show that structural and functional abnormalities
      of the ACC and pSTG occur during LLD remission. Our findings tentatively reveal
      the brain pathophysiology involved in LLD and may aid in developing
      neuroanatomical biomarkers for this condition.

PMID- 29472856
TI  - Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway.
AB  - Tumor metastasis is the most lethal and debilitating process that threatens
      cancer patients. Among the regulators involved in tumor metastasis, lysyl oxidase
      (LOX) is an important contributor for tumor invasion, migration and the formation
      of the pre-metastatic niche. Although the relationship between LOX and poor
      prognosis of lung patients has been preliminary reported, the mechanism remains
      poorly understood. Here, we found that LOX overexpression is closely related to
      the survival of lung adenocarcinoma patients but not squamous cell carcinoma
      patients. Moreover, we confirmed that LOX expression is regulated by the
      activation of epidermal growth factor receptor (EGFR) via the PI3K/AKT, MEK/ERK,
      and SAPK/JNK signaling pathways in non-small cell lung cancer (NSCLC). Meanwhile,
      the study also suggested that the traditional anti-fibrosis drug silibinin
      inhibited NSCLC cell migration in an EGFR/LOX dependent manner. In addition, an
      orthotopic implantation metastasis model also confirmed that the EGFR inhibitor
      WZ4002 and silibinin decreased tumor metastasis through the EGFR/LOX pathway.
      Altogether, this study revealed that LOX expression is regulated by the EGFR
      pathway and this may account for the anti-cancer metastasis effects of silibinin,
      indicating LOX as a potentially therapeutic target for NSCLC treatment.

PMID- 29472857
TI  - Contributions of the Nucleus Accumbens Shell in Mediating the Enhancement in
      Memory Following Noradrenergic Activation of Either the Amygdala or Hippocampus.
AB  - The nucleus accumbens shell is a site of converging inputs during memory
      processing for emotional events. The accumbens receives input from the nucleus of
      the solitary tract (NTS) regarding changes in peripheral autonomic functioning
      following emotional arousal. The shell also receives input from the amygdala and
      hippocampus regarding affective and contextual attributes of new learning
      experiences. The successful encoding of affect or context is facilitated by
      activating noradrenergic systems in either the amygdala or hippocampus. Recent
      findings indicate that memory enhancement produced by activating NTS neurons, is
      attenuated by suppressing accumbens functioning after learning. This finding
      illustrates the significance of the shell in integrating information from the
      periphery to modulate memory for arousing events. However, it is not known if the
      accumbens shell plays an equally important role in consolidating information that
      is initially processed in the amygdala and hippocampus. The present study
      determined if the convergence of inputs from these limbic regions within the
      nucleus accumbens contributes to successful encoding of emotional events into
      memory. Male Sprague-Dawley rats received bilateral cannula implants 2 mm above
      the accumbens shell and a second bilateral implant 2 mm above either the amygdala
      or hippocampus. The subjects were trained for 6 days to drink from a water spout.
      On day 7, a 0.35 mA footshock was initiated as the rat approached the spout and
      was terminated once the rat escaped into a white compartment. Subjects were then
      given intra-amygdala or hippocampal infusions of PBS or a dose of norepinephrine
      (0.2 MUg) previously shown to enhance memory. Later, all subjects were given
      intra-accumbens infusion of muscimol to functionally inactivate the shell.
      Muscimol inactivation of the accumbens shell was delayed to allow sufficient time
      for norepinephrine to activate intracellular cascades that lead to long-term
      synaptic modifications involved in forming new memories. Results show that memory
      improvement produced by infusing norepinephrine in either the amygdala or
      hippocampus is attenuated by interrupting neuronal activity in the shell 1 or 7 7
      h following amygdala or hippocampus activation. These findings suggest that the
      accumbens shell plays an integral role modulating information initially processed
      by the amygdala and hippocampus following exposure to emotionally arousing
      events. Additionally, results demonstrate that the accumbens is involved in the
      long-term consolidation processes lasting over 7 h.

PMID- 29472858
TI  - An Integrated Lipidomics and Phenotype Study Reveals Protective Effect and
      Biochemical Mechanism of Traditionally Used Alisma orientale Juzepzuk in Chronic
      Kidney Disease.
AB  - Alisma orientale Juzepzuk (AO) is widely used for various diuretic and
      nephropathic treatments in traditional Chinese medicines (TCM). In a clinical
      setting, AO is used as both a lipid-lowering and tubular interstitial fibrosis
      agent. However, the mechanisms of AO for the treatment of renal interstitial
      fibrosis and abnormal lipid metabolism are not well-understood. In this study,
      pharmacological and UPLC-HDMS-based lipidomic approaches were employed to
      investigate the lipid-lowering and tubular interstitial fibrosis effect of AO on
      rats with adenine-induced chronic kidney disease (CKD). Rats with CKD showed
      increased serum levels of creatinine and urea, tubular damage, and tubular
      interstitial fibrosis. Moreover, multiple lipid species were identified in CKD
      rats. Among these lipids, polyunsaturated fatty acid, eicosapentaenoic acid, 8,9
      epoxyeicosatrienoic acid, and docosahexaenoic acid levels were significantly
      decreased in CKD rats compared to control rats. In CKD rats, up-regulation of the
      NF-kappaB pathway may impair polyunsaturated fatty acid metabolism, causing renal
      fibrosis. In addition, CKD rats showed significantly decreased diglyceride levels
      and increased triglyceride levels compared to the control group. Pathway over
      representation analysis demonstrated that 30 metabolic pathways were associated
      with lipid species. AO treatment suppressed up-regulation of inflammation, and
      partly restored the deregulation of polyunsaturated fatty acids and glycerolipids
      metabolism. Our results indicated that AO treatment attenuated renal fibrosis by
      down-regulating inflammation, and mitigating lipid metabolism in CKD rats. In
      conclusion, this study has identified the therapeutic lipid-lowering and anti
      fibrosis effects of AO on CKD.

PMID- 29472855
TI  - Role of Copper in the Onset of Alzheimer's Disease Compared to Other Metals.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by
      amyloid plaques in patients' brain tissue. The plaques are mainly made of beta
      amyloid peptides and trace elements including Zn2+, Cu2+, and Fe2+. Some studies
      have shown that AD can be considered a type of metal dyshomeostasis. Among metal
      ions involved in plaques, numerous studies have focused on copper ions, which
      seem to be one of the main cationic elements in plaque formation. The involvement
      of copper in AD is controversial, as some studies show a copper deficiency in AD,
      and consequently a need to enhance copper levels, while other data point to
      copper overload and therefore a need to reduce copper levels. In this paper, the
      role of copper ions in AD and some contradictory reports are reviewed and
      discussed.

PMID- 29472859
TI  - Zinc Oxide Nanoparticle Caused Plasma Metabolomic Perturbations Correlate with
      Hepatic Steatosis.
AB  - Zinc oxide nanoparticles (ZnO NPs), known for their chemical stability and strong
      adsorption, are used in everyday items such as cosmetics, sunscreens, and
      prophylactic drugs. However, they have also been found to adversely affect
      organisms; previously we found that ZnO NPs disrupt pubertal ovarian development,
      inhibit embryonic development by upsetting gamma-H2AX and NF-kappaB pathways, and
      even disturb skin stem cells. Non-targeted metabolomic analysis of biological
      organisms has been suggested as an unbiased tool for the investigation of
      perturbations in response to NPs and their underlying mechanisms. Although
      metabolomics has been used in nanotoxicological studies, very few reports have
      used it to investigate the effects of ZnO NPs exposure. In the current
      investigation, through a metabolomics-based approach, we discovered that ZnO NPs
      caused changes in plasma metabolites involved in anti-oxidative mechanisms,
      energy metabolism, and lipid metabolism in hen livers. These results are in line
      with earlier findings that ZnO NPs perturb the tricarboxylic acid cycle and in
      turn result in the use of alternative energy sources. We also found that ZnO NPs
      disturbed lipid metabolism in the liver and consequently impacted blood lipid
      balance. Changes in plasma metabolomes were correlated with hepatic steatosis.

PMID- 29472860
TI  - Magnesium Lithospermate B Protects against Lipopolysaccharide-Induced Bone Loss
      by Inhibiting RANKL/RANK Pathway.
AB  - Lipopolysaccharide (LPS) can induce bone loss by stimulating bone resorption.
      Natural compounds have great potential for the treatment of osteolytic bone
      diseases. Magnesium lithospermate B (MLB) plays an important role in protecting
      against oxidative damage and also has potential anti-inflammatory pharmacological
      properties. However, its role in LPS-induced bone loss is still unknown. In the
      present study, we observed the effects of MLB on LPS-induced bone damage and
      investigated the possible mechanisms. The bone loss models were established by
      LPS administration in male Sprague-Dawley rats. MLB (200 mg/kg body weight) was
      given by subcutaneous injection. MicroCT analysis, biomarker assay, histological
      examination and immunohistochemical staining were performed at the 8th weeks. In
      addition, RAW264.7 cells were treated with LPS in the presence or absence of MLB.
      The osteoclast formation, resorption activity and differentiation-related genes
      [(receptor activator of nuclear factor kappa-B (RANK), Traf6, Fra-1, and c-src)]
      expression were evaluated. LPS induced bone loss shown as the decrease in bone
      volume fraction and trabecular number, and increase in trabecular separation. LPS
      also markedly enhanced the osteoclast formation and resorption activity compared
      with the control. MLB significantly abolished the LPS-induced bone microstructure
      damage (p < 0.05) and osteoclast formation. MLB also inhibited the increases of
      serum tartrate-resistant acid phosphatase 5b, RANK ligand (RANKL) and TNF-alpha
      level enhanced by LPS (p < 0.05). Immunohistochemical staining indicated that MLB
      attenuated the high expression of RANKL and RANK stimulated by LPS. In addition,
      MLB significantly abolished the LPS-enhanced osteoclast formation, resorption
      activity, RANK, Traf6, Fra-1, and c-src expression in vitro. Our data demonstrate
      that MLB can suppress LPS-induced bone loss via inhibiting RANKL/RANK related
      osteoclast formation.

PMID- 29472861
TI  - 1,2,3,4,6-Penta-O-Galloyl-Beta-D-Glucopyranoside Inhibits Proliferation of
      Multiple Myeloma Cells Accompanied with Suppression of MYC Expression.
AB  - Multiple myeloma (MM) still remains an incurable disease, therefore discovery of
      novel drugs boosts the therapeutics for MM. The natural compound 1,2,3,4,6-Penta
      O-galloyl-beta-D-glucopyranoside (PGG) has been shown to exhibit antitumor
      activities against various cancer cells. Here, we aim to evaluate antitumor
      effects of PGG on MM cell lines. PGG inhibited the growth of three different MM
      cell lines in a dose- and time-dependent manner. Cell cycle analysis revealed
      that PGG treatment caused cell cycle arrest in G1 phase. It also induced
      apoptosis which was indicated by significant increases of Annexin V positive
      cells, caspase 3/7 activity, and cleaved caspase 3 expression in PGG treated MM
      cell. Since MYC is frequently hyperactivated in MM and inhibition of MYC leads to
      MM cell death. We further demonstrated that PGG decreased MYC expression in
      protein and mRNA levels and reversed the mRNA expression of MYC target genes such
      as p21, p27, and cyclin D2. In addition, PGG also reduced protein expression of
      DEPTOR which is commonly overexpressed in MM. Unexpectedly, PGG antagonized the
      cytotoxic effect of bortezomib in the combination treatment. However, PGG
      treatment sensitized MM cells to another proteasome inhibitor MG132 induced
      cytotoxicity. Moreover, MYC inhibitor JQ1 enhanced the cytotoxic effect of
      bortezomib on MM cells. Our findings raised concerns about the combinatory use of
      bortezomib with particular types of chemicals. The evidence also provide useful
      insights into the combination of MYC and proteasome-inhibitors for MM therapy.
      Finally, PGG has a therapeutic potential for treatment of MM and further
      development is mandatory.

PMID- 29472862
TI  - Complete Genome Sequence and Genomic Characterization of Lactobacillus
      acidophilus LA1 (11869BP).

PMID- 29472863
TI  - beta2-Adrenergic Receptor Activation Suppresses the Rat Phenethylamine
      Hallucinogen-Induced Head Twitch Response: Hallucinogen-Induced Excitatory Post
      synaptic Potentials as a Potential Substrate.
AB  - 5-Hydroxytryptamine2A (5-HT2A) receptors are enriched in layers I and Va of the
      rat prefrontal cortex and neocortex and their activation increases the frequency
      of glutamatergic excitatory post-synaptic potentials/currents (EPSP/Cs) onto
      layer V pyramidal cells. A number of other G-protein coupled receptors (GPCRs)
      are also enriched in cortical layers I and Va and either induce (alpha1
      adrenergic and orexin2) or suppress (metabotropic glutamate2 [mGlu2], adenosine
      A1, MU-opioid) both 5-HT-induced EPSCs and head twitches or head shakes induced
      by the phenethylamine hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI). Another
      neurotransmitter receptor also localized to apparent thalamocortical afferents to
      layers I and Va of the rat prefrontal cortex and neocortex is the beta2
      adrenergic receptor. Therefore, we conducted preliminary electrophysiological
      experiments with rat brain slices examining the effects of epinephrine on
      electrically-evoked EPSPs following bath application of DOI (3 MUM). Epinephrine
      (0.3-10 MUM) suppressed the late EPSPs produced by electrical stimulation and
      DOI. The selective beta2-adrenergic receptor antagonist ICI-118,551 (300 nM)
      resulted in a rightward shift of the epinephrine concentration-response
      relationship. We also tested the selective beta2-adrenergic receptor agonist
      clenbuterol and the antagonist ICI-118,551 on DOI-induced head twitches.
      Clenbuterol (0.3-3 mg/kg, i.p.) suppressed DOI (1.25 mg/kg, i.p.)-induced head
      twitches. This clenbuterol effect appeared to be at least partially reversed by
      the selective beta2-adrenergic receptor antagonist ICI-118,553 (0.01-1 mg/kg,
      i.p.), with significant reversal at doses of 0.1 and 1 mg/kg. Thus, beta2
      adrenergic receptor activation reverses the effects of phenethylamine
      hallucinogens in the rat prefrontal cortex. While Gi/Go-coupled GPCRs have
      previously been shown to suppress both the electrophysiological and behavioral
      effects of 5-HT2A receptor activation in the mPFC, the present work appears to
      extend this suppressant action to a Gs-coupled GPCR. Furthermore, the modulation
      of 5-HT2A receptor activation-induced glutamate release onto mPFC layer V
      pyramidal neurons apical dendrites by a range GPCRs in rat brain slices appears
      to results in behaviorally salient effects of relevance when screening for novel
      CNS therapeutic drugs.

PMID- 29472864
TI  - Paeonol Inhibits Oxidized Low-Density Lipoprotein-Induced Vascular Endothelial
      Cells Autophagy by Upregulating the Expression of miRNA-30a.
AB  - Paeonol from Cortex Moutan root is a potential therapeutic agent for
      atherosclerosis (AS). However, its mechanisms of action are still not fully
      understood. Vascular endothelial cells (VECs) autophagy plays a vital role in the
      initiation and progression of AS. In this study, we aim to investigate whether
      the protective effect of paeonol on ox-LDL-induced VECs injury by regulating
      autophagy. To address this question, we used ox-LDL-induced rat VECs as a model
      system to elucidate the protective effect of paeonol on VECs injury. This study
      displayed that ox-LDL (100 mg/L) treatment inhibited VEC growth in dose- and time
      dependent manners, paeonol (60 MUM) shown potential in inhibiting ox-LDL-induced
      death. Furthermore, paeonol significantly reduced ox-LDL-induced the formation of
      autophagy vacuoles and the expression of LC3II in VECs. Further double-luciferase
      reporter assay shown that miR-30a specifically binds to the 3'-UTR of Beclin-1
      mRNA in VECs. Moreover, we found that ox-LDL decreased miR-30a and increased
      Beclin-1 expression, pretreatment with paeonol could reverse the process of
      regulation in dose-dependent manners. In ox-LDL treated VECs, transfection with a
      miR-30a mimic significantly increased miR-30a expression and inhibited Beclin-1
      and LC3II expression, thus enhanced the protective effects of paeonol. Whereas
      transfection with a miR-30a inhibitor significantly decreased miR-30a expression
      and increased Beclin-1 and LC3II expression, thus attenuated the protective
      effects of paeonol. In conclusion, this study has, for the ?rst time, highlighted
      that miR-30a might be a critical target of paeonol against ox-LDL-induced VECs
      injury by inhibiting excessive autophagy. Paeonol may be one of promising
      candidate drug for treatment of AS.

PMID- 29472865
TI  - Intracranial Pressure Is a Determinant of Sympathetic Activity.
AB  - Intracranial pressure (ICP) is the pressure within the cranium. ICP rise
      compresses brain vessels and reduces cerebral blood delivery. Massive ICP rise
      leads to cerebral ischemia, but it is also known to produce hypertension,
      bradycardia and respiratory irregularities due to a sympatho-adrenal mechanism
      termed Cushing response. One still unresolved question is whether the Cushing
      response is a non-synaptic acute brainstem ischemic mechanism or part of a larger
      physiological reflex for arterial blood pressure control and homeostasis
      regulation. We hypothesize that changes in ICP modulates sympathetic activity.
      Thus, modest ICP increase and decrease were achieved in mice and patients with
      respectively intra-ventricular and lumbar fluid infusion. Sympathetic activity
      was gauged directly by microneurography, recording renal sympathetic nerve
      activity in mice and muscle sympathetic nerve activity in patients, and gauged
      indirectly in both species by heart-rate variability analysis. In mice (n = 15),
      renal sympathetic activity increased from 29.9 +/- 4.0 bursts.s-1 (baseline ICP
      6.6 +/- 0.7 mmHg) to 45.7 +/- 6.4 bursts.s-1 (plateau ICP 38.6 +/- 1.0 mmHg) and
      decreased to 34.8 +/- 5.6 bursts.s-1 (post-infusion ICP 9.1 +/- 0.8 mmHg). In
      patients (n = 10), muscle sympathetic activity increased from 51.2 +/- 2.5
      bursts.min-1 (baseline ICP 8.3 +/- 1.0 mmHg) to 66.7 +/- 2.9 bursts.min-1
      (plateau ICP 25 +/- 0.3 mmHg) and decreased to 58.8 +/- 2.6 bursts.min-1 (post
      infusion ICP 14.8 +/- 0.9 mmHg). In patients 7 mmHg ICP rise significantly
      increases sympathetic activity by 17%. Heart-rate variability analysis
      demonstrated a significant vagal withdrawal during the ICP rise, in accordance
      with the microneurography findings. Mice and human results are alike. We
      demonstrate in animal and human that ICP is a reversible determinant of efferent
      sympathetic outflow, even at relatively low ICP levels. ICP is a biophysical
      stress related to the forces within the brain. But ICP has also to be considered
      as a physiological stressor, driving sympathetic activity. The results suggest a
      novel physiological ICP-mediated sympathetic modulation circuit and the existence
      of a possible intracranial (i.e., central) baroreflex. Modest ICP rise might
      participate to the pathophysiology of cardio-metabolic homeostasis imbalance with
      sympathetic over-activity, and to the pathogenesis of sympathetically-driven
      diseases.

PMID- 29472866
TI  - Hypoxia Exacerbates Negative Emotional State during Inactivity: The Effect of 21
      Days Hypoxic Bed Rest and Confinement.
AB  - Hypoxia and confinement have both been shown to influence emotional state. It is
      envisaged that the inhabitants of future planetary habitats will be exposed to
      concomitant confinement, reduced gravity and hypoxia. We examined the independent
      and combined effects of a 21-day inactivity/unloading and normobaric hypoxia
      under confined conditions on various psychological factors. Eleven healthy men
      participated in three 21-day experimental campaigns designed in a cross-over
      manner: (1) Normobaric hypoxic ambulatory confinement, (2) Normobaric hypoxic bed
      rest and (3) Normobaric normoxic bed rest. The Profile of Mood States, and the
      Positive and Negative Affect Schedule were employed to assess the participants'
      psychological responses before (Pre), during (Day 7, Day 14, and Day 21) and
      after (Post) the confinements. The most negative psychological profile appeared
      on days 14 and 21 of the hypoxic bed rest campaign. A significant increase in
      depression, tension, and confusion was noted on days 14 and 21 of the hypoxic bed
      rest condition. Concomitantly, a decrease, albeit not statistically significant,
      in positive psychological responses was observed. The psychological profile
      returned to the initial level at Post following all confinements. These data
      suggest that the combined effect of hypoxia and bed rest induced the most
      negative effects on an individual's mood. However, significant intra- and inter
      individual differences in psychological responses were noted and should be taken
      into consideration.

PMID- 29472867
TI  - Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators
      and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and
      Oleylethanolamide Levels in Rat Skeletal Muscle.
AB  - Scope: Milk from various species differs in nutrient composition. In particular,
      human milk (HM) and donkey milk (DM) are characterized by a relative high level
      of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats
      seem to exert beneficial nutritional properties through N-acylethanolamine tissue
      modulation. The aim of this study is to compare the effects of cow milk (CM), DM,
      and HM on inflammation and glucose and lipid metabolism, focusing on
      mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the
      major determinant of resting metabolic rate. Moreover, we also evaluated the
      levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle,
      since tissue fatty acid profiles can be modulated by nutrient intervention.
      Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then,
      glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti
      inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal
      muscle was also processed to estimate mitochondrial function, efficiency, and
      dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty
      acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined
      in liver and skeletal muscle tissue. Results: We demonstrated that DM or HM
      administration reducing inflammation status, improves glucose disposal and
      insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover,
      HM or DM administration increases redox status, and mitochondrial uncoupling,
      affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM
      supplementation increase liver and muscle levels of the N-oleoylethanolamine
      (OEA), a key regulator of lipid metabolism and inflammation. Conclusions: HM and
      DM have a healthy nutritional effect, acting on inflammatory factors and glucose
      and lipid metabolism. This beneficial effect is associated to a modulation of
      mitochondrial function, efficiency, and dynamics and to an increase of OEA levels
      in skeletal muscle.

PMID- 29472868
TI  - Niemann-Pick C2 Proteins: A New Function for an Old Family.
AB  - Niemann-Pick proteins type C2 (NPC2) are carriers of cholesterol in vertebrates,
      with a single member in each species. The high sequence conservation between
      mammals and across vertebrates is related to their common function. In contrast,
      NPC2 proteins in arthropods have undergone extensive duplication and
      differentiation, probably under environmental pressure, and are likely to have
      different functions. Recent studies have suggested that in arthropods these
      proteins might act as carriers for semiochemicals and other hydrophobic
      compounds. In this study we focused on the function of a specific NPC2 gene in
      the moth Helicoverpa armigera (HarmNPC2-1). This protein binds several flavonoids
      with micromolar dissociation constants. The best ligand was gossypol, present in
      cotton, one of the main host plants for H. armigera. Western blot revealed the
      presence of HarmNPC2-1 in different parts of the body, including the antennae,
      proboscis, and abdomen. In the antennae, in situ hybridization experiments
      produced strong staining in auxiliary cells at the base of sensilla trichodea,
      basiconica, coeloconica, and chaetica. Immunocytochemistry confirmed the
      expression of the protein in sensilla chaetica. Our results support a role of
      semiochemical carriers for NPC2 proteins in insects and indicate such proteins as
      new targets for insecticide-free pest population control.

PMID- 29472869
TI  - Phosphorylated and Non-phosphorylated Leucine Rich Amelogenin Peptide
      Differentially Affect Ameloblast Mineralization.
AB  - The Leucine Rich Amelogenin Peptide (LRAP) is a product of alternative splicing
      of the amelogenin gene. As full length amelogenin, LRAP has been shown, in
      precipitation experiments, to regulate hydroxyapatite (HAP) crystal formation
      depending on its phosphorylation status. However, very few studies have
      questioned the impact of its phosphorylation status on enamel mineralization in
      biological models. Therefore, we have analyzed the effect of phosphorylated (+P)
      or non-phosphorylated (-P) LRAP on enamel formation in ameloblast-like cell lines
      and ex vivo cultures of murine postnatal day 1 molar germs. To this end, the
      mineral formed was analyzed by micro-computed tomography, Field Emission Scanning
      Electron Microscopy, Transmission Electron Microscopy, Selected Area Electon
      Diffraction imaging. Amelogenin gene transcription was evaluated by qPCR
      analysis. Our data show that, in both cells and germ cultures, LRAP is able to
      induce an up-regulation of amelogenin transcription independently of its
      phosphorylation status. Mineral formation is promoted by LRAP(+P) in all models,
      while LRAP(-P) essentially affects HAP crystal formation through an increase in
      crystal length and organization in ameloblast-like cells. Altogether, these data
      suggest a differential effect of LRAP depending on its phosphorylation status and
      on the ameloblast stage at the time of treatment. Therefore, LRAP isoforms can be
      envisioned as potential candidates for treatment of enamel lesions or defects and
      their action should be further evaluated in pathological models.

PMID- 29472870
TI  - High-Intensity Interval Training in Normobaric Hypoxia Leads to Greater Body Fat
      Loss in Overweight/Obese Women than High-Intensity Interval Training in Normoxia.
AB  - A moderate hypoxic stimulus is considered a promising therapeutic modality for
      several pathological states including obesity. There is scientific evidence
      suggesting that when hypoxia and physical activity are combined, they could
      provide benefits for the obese population. The aim of the present study was to
      investigate if exposure to hypoxia combined with two different protocols of high
      intensity interval exercise in overweight/obese women was more effective compared
      with exercise in normoxia. Study participants included 82 overweight/obese women,
      who started a 12 week program of 36 sessions, and were randomly divided into four
      groups: (1) aerobic interval training in hypoxia (AitH; FiO2 = 17.2%; n = 13),
      (2) aerobic interval training in normoxia (AitN; n = 15), (3) sprint interval
      training in hypoxia (SitH; n = 15), and (4) sprint interval training in normoxia
      (SitN; n = 18). Body mass, body mass index, percentage of total fat mass, muscle
      mass, basal metabolic rate, fat, and carbohydrate oxidation, and fat and
      carbohydrate energy were assessed. Outcomes were measured at baseline (T1), after
      18 training sessions (T2), 7 days after the last session (T3), and 4 weeks after
      the last session (T4). The fat mass in the SitH group was significantly reduced
      compared with the SitN group from T1 to T3 (p < 0.05) and from T1 to T4 (p <
      0.05) and muscle mass increased significantly from T1 to T4 (p < 0.05). Fat mass
      in the AitH group decreased significantly (p < 0.01) and muscle mass increased (p
      = 0.022) compared with the AitN group from T1 to T4. All training groups showed a
      reduction in the percentage of fat mass, with a statistically significant
      reduction in the hypoxia groups (p < 0.05). Muscle mass increased significantly
      in the hypoxia groups (p < 0.05), especially at T4. While fat oxidation tended to
      increase and oxidation of carbohydrates tended to decrease in both hypoxia
      groups, the tendency was reversed in the normoxia groups. Thus, high-intensity
      interval training under normobaric intermittent hypoxia for 12 weeks in
      overweight/obese women seems to be promising for reducing body fat content with a
      concomitant increase in muscle mass.

PMID- 29472871
TI  - A Comparison between Different Methods of Estimating Anaerobic Energy Production.
AB  - Purpose: The present study aimed to compare four methods of estimating anaerobic
      energy production during supramaximal exercise. Methods: Twenty-one junior cross
      country skiers competing at a national and/or international level were tested on
      a treadmill during uphill (7 degrees ) diagonal-stride (DS) roller-skiing. After
      a 4-minute warm-up, a 4 * 4-min continuous submaximal protocol was performed
      followed by a 600-m time trial (TT). For the maximal accumulated O2 deficit
      (MAOD) method the [Formula: see text]O2-speed regression relationship was used to
      estimate the [Formula: see text]O2 demand during the TT, either including (4+Y,
      method 1) or excluding (4-Y, method 2) a fixed Y-intercept for baseline [Formula:
      see text]O2. The gross efficiency (GE) method (method 3) involved calculating
      metabolic rate during the TT by dividing power output by submaximal GE, which was
      then converted to a [Formula: see text]O2 demand. An alternative method based on
      submaximal energy cost (EC, method 4) was also used to estimate [Formula: see
      text]O2 demand during the TT. Results: The GE/EC remained constant across the
      submaximal stages and the supramaximal TT was performed in 185 +/- 24 s. The GE
      and EC methods produced identical [Formula: see text]O2 demands and O2 deficits.
      The [Formula: see text]O2 demand was ~3% lower for the 4+Y method compared with
      the 4-Y and GE/EC methods, with corresponding O2 deficits of 56 +/- 10, 62 +/-
      10, and 63 +/- 10 mL.kg-1, respectively (P < 0.05 for 4+Y vs. 4-Y and GE/EC). The
      mean differences between the estimated O2 deficits were -6 +/- 5 mL.kg-1 (4+Y vs.
      4-Y, P < 0.05), -7 +/- 1 mL.kg-1 (4+Y vs. GE/EC, P < 0.05) and -1 +/- 5 mL.kg-1
      (4-Y vs. GE/EC), with respective typical errors of 5.3, 1.9, and 6.0%. The mean
      difference between the O2 deficit estimated with GE/EC based on the average of
      four submaximal stages compared with the last stage was 1 +/- 2 mL.kg-1, with a
      typical error of 3.2%. Conclusions: These findings demonstrate a disagreement in
      the O2 deficits estimated using current methods. In addition, the findings
      suggest that a valid estimate of the O2 deficit may be possible using data from
      only one submaximal stage in combination with the GE/EC method.

PMID- 29472872
TI  - Pharmacoresistant Severe Mental Health Disorders in Children and Adolescents:
      Functional Abnormalities of Cytochrome P450 2D6.
AB  - Background: Severe mental health disorders in children and adolescents represent
      a major public health problem. Despite adequate drug treatment, some patients
      develop pharmacoresistant disease. As a consequence, physicians are confronted
      with prescribing challenges, prolonged hospitalization and increased risk of
      adverse events, thus aggravating short-, medium-, and long-term prognosis. The
      majority of psychotropic treatments, particularly antipsychotics and
      antidepressants, are metabolized at hepatic level by cytochrome P450 (CYP),
      particularly by CYP3A4 and CYP2D6. Several CYP2D6 genetic polymorphisms are
      described to be associated with ultrarapid (UM) or poor drug metabolism (PM),
      inducing clinical resistance and/or adverse events, and might therefore be
      related to pharmacoresistant severe mental health disease. Case presentation: A
      total of nine pharmacoresistant patients (four females, five males) aged 11-16
      (mean 14.1) years have been genotyped for CYP2D6 between January, 2015 and April,
      2016. Patients were diagnosed with schizophrenia (n = 5), autism spectrum
      disorders (n = 2), intellectual disability with challenging behavior (n = 2),
      oppositional defiant disorder (n = 1), and post-traumatic stress and borderline
      personality disorders (n = 1). They had a treatment history with on average 6.1
      (3-9) psychotropic, 5 (3-7) antipsychotic, and 3.4 (2-5) CYP2D6-metabolized
      antipsychotic and antidepressant molecules. Five patients (56%) presented
      functional anomalies of the CYP2D6 gene: three patients were UM metabolizers with
      gene duplication and two patients were PM with *4/*41 and *3/*4 polymorphisms.
      Conclusion: Functional anomalies of CYP2D6 concerned more than half of our
      pediatric inpatient sample with pharmacoresistant disease. However, our case
      reports are limited by the low sample size. Nevertheless, knowledge of individual
      metabolism and in particular CYP2D6 genotyping should be considered for clinical
      workup and therapy adjustment in resistant patients in child and adolescent
      psychiatry and might permit better treatment outcome, increased treatment
      adherence and diminished adverse events.

PMID- 29472873
TI  - Facial Recognition of Happiness Is Impaired in Musicians with High Music
      Performance Anxiety.
AB  - Introduction: Music performance anxiety (MPA) can be defined as a lasting and
      intense apprehension connected with musical performance in public. Studies
      suggest that MPA can be regarded as a subtype of social anxiety. Since
      individuals with social anxiety have deficits in the recognition of facial
      emotion, we hypothesized that musicians with high levels of MPA would share
      similar impairments. Objective: The aim of this study was to compare parameters
      of facial emotion recognition (FER) between musicians with high and low MPA.
      Methods: 150 amateur and professional musicians with different musical
      backgrounds were assessed in respect to their level of MPA and completed a
      dynamic FER task. The outcomes investigated were accuracy, response time,
      emotional intensity, and response bias. Results: Musicians with high MPA were
      less accurate in the recognition of happiness (p = 0.04; d = 0.34), had increased
      response bias toward fear (p = 0.03), and increased response time to facial
      emotions as a whole (p = 0.02; d = 0.39). Conclusion: Musicians with high MPA
      displayed FER deficits that were independent of general anxiety levels and
      possibly of general cognitive capacity. These deficits may favor the maintenance
      and exacerbation of experiences of anxiety during public performance, since cues
      of approval, satisfaction, and encouragement are not adequately recognized.

PMID- 29472874
TI  - Validation of the Portuguese Version of Impulsive-Premeditated Aggression Scale
      in an Inmate Population.
AB  - Aggression is one of the core symptoms of antisocial personality disorder (ASPD)
      with therapeutic and prognostic relevance. ASPD is highly prevalent among
      inmates, being responsible for adverse events and elevated direct and indirect
      economic costs for the criminal justice system. The Impulsive/Premeditated
      Aggression Scale (IPAS) is a self-report instrument that characterizes aggression
      as either predominately impulsive or premeditated. This study aims to determine
      the validity and reliability of the IPAS in a sample of Portuguese inmates. A
      total of 240 inmates were included in the study. A principal component factor
      analysis was performed so as to obtain the construct validity of the IPAS
      impulsive aggression (IA) and premeditated aggression (PM) subscales; internal
      consistency was determined by Cronbach's alpha coefficient; convergent and
      divergent validity of the subscales were determined analyzing correlations with
      the Barratt Impulsiveness scale, 11th version (BIS-11), and the Psychopathic
      Checklist Revised (PCL-R). The rotated matrix with two factors accounted for
      49.9% of total variance. IA subscale had 11 items and PM subscale had 10 items.
      The IA and PM subscales had a good Cronbach's alpha values of 0.89 and 0.88,
      respectively. The IA subscale is correlated with BIS-11 attentional, motor, and
      non-planning impulsiveness dimensions (p < 0.05). The PM subscale is correlated
      with BIS-11 attentional, motor impulsiveness dimensions (p < 0.05). The PM
      subscale is correlated with PCL-R interpersonal, lifestyle, and antisocial
      dimensions (p < 0.05). The IA subscale is not correlated with PCL-R. The
      Portuguese translated version of IPAS has adequate psychometric properties,
      allowing the measurement of impulsive and premeditated dimensions of aggression.

PMID- 29472875
TI  - Anxiety and Depression in Drug-Dependent Patients with Cluster C Personality
      Disorders.
AB  - Objective: Comorbidity between personality disorders (PD) and substance-use
      disorders (SUD) is one of the most common findings in the psychiatric field. The
      patients with Cluster C disorders present maladjustment traits often
      characterized by high levels of anxiety. The main aim of this study was to find
      evidences about higher anxiety and depression prevalence on Cluster C than others
      Clusters, analyzing similarities and differences within, with other Cluster A and
      B PD patients and patients without PD. Method: A total of 822 substance dependent
      patients (ages18-78; Mean = 38.35, SD = 10.14) completed the structured clinical
      interview for DSM-IV Axis I and Axis II disorders, Beck Depression Inventory, and
      State-Trait Anxiety Inventory. Results: Results supported poly-consumption in
      Cluster C patients, being greater alcohol consumption as well as abuse of both
      stimulants and depressants. Anxiety and depression did not show just one pattern
      for all patients with SUD-Cluster C PD. There was a relation between anxiety and
      depression for all the groups except for the Dependent-PD. Conclusion:
      Interventions should focus on aspects like depression and anxiety more than on
      the substance consumed.

PMID- 29472877
TI  - Commentary: Why Your Body Can Jog Your Mind.

PMID- 29472876
TI  - Psychopathology Assessment Methods Revisited: On Translational Cross-Validation
      of Clinical Self-Evaluation Scale and fMRI.
AB  - We present in this article a study design that combines clinical self-assessment
      scale, simultaneously administered with fMRI data acquisition. We have used a
      standard block-design with two different conditions. Each active block consisted
      of four text statements (items), alternating diagnostically specific (DS) blocks
      comprising items from von Zerssen depression scale and diagnostically neutral
      (DN) blocks with items from a questionnaire about general interests. All items
      were rated on four degree Likert scale, and patients provided responses with
      corresponding four buttons during the fMRI session. Our results demonstrated that
      in healthy controls, contrasting the two types of stimuli yielded no residual
      activations, e.g., the DS did not produce significantly different activations
      compared to the DN stimuli. Furthermore, the correlation analyses did not find a
      relationship between brain activations and the total score of the DS statements
      in this group. However, contrasting the DS stimuli to the DN stimuli in the
      patients produced significant residual activations in several brain regions:
      right pre- and postcentral gyrus (including right supramarginal gyrus), left
      middle frontal gyrus, triangular part of the left inferior frontal gyrus and
      middle temporal gyrus. The left precuneus demonstrated correlations with the
      patients' DS score. In the between-group comparisons, we found residual
      activations in the right pre- and postcentral gyrus, right supplementary motor
      area, medial segment of the right precentral gyrus, right superior parietal
      lobule, left middle frontal gyrus, left superior frontal gyrus, left occipital
      pole. Our results confirm the possibility of translational cross-validation of a
      clinical psychological test (von Zerssen's depression scale) and fMRI. At this
      stage, however, we can only confirm the sensitivity of the method (its ability to
      distinguish healthy controls from depressed patients), but we cannot conclude
      anything about its specificity (distinction from different psychopathology
      conditions).

PMID- 29472878
TI  - The Effects of Martial Arts Training on Attentional Networks in Typical Adults.
AB  - There is substantial evidence that training in Martial Arts is associated with
      improvements in cognitive function in children; but little has been studied in
      healthy adults. Here, we studied the impact of extensive training in Martial Arts
      on cognitive control in adults. To do so, we used the Attention Network Test
      (ANT) to test two different groups of participants: with at least 2 years of
      Martial Arts experience, and with no experience with the sport. Participants were
      screened from a wider sample of over 500 participants who volunteered to
      participate. 48 participants were selected: 21 in the Martial Arts group (mean
      age = 19.68) and 27 in the Non-Martial Arts group (mean age = 19.63). The two
      groups were matched on a number of demographic variables that included Age and
      BMI, following the results of a previous pilot study where these factors were
      found to significantly impact the ANT measures. An effect of Martial Arts
      experience was found on the Alert network, but not the Orienting or Executive
      ones. More specifically, Martial Artists showed improved performance when alert
      had to be sustained endogenously, performing more like the control group when an
      exogenous cue was provided. This result was further confirmed by a negative
      correlation between number of years of Martial Arts experience and the costs due
      to the lack of an exogenous cue suggesting that the longer a person takes part in
      the sport, the better their endogenous alert is. Results are interpreted in the
      context of the impact of training a particular attentional state in specific
      neurocognitive pathways.

PMID- 29472879
TI  - Transdermal Optical Imaging Reveal Basal Stress via Heart Rate Variability
      Analysis: A Novel Methodology Comparable to Electrocardiography.
AB  - The present study examined the validity of a novel physiological measurement
      technology called transdermal optical imaging (TOI) technology at assessing basal
      stress. This technology conveniently, contactlessly, and remotely measures facial
      blood flow changes using a conventional digital video camera. We compared data
      from TOI against the pulse data collected from the FDA approved BIOPAC system.
      One hundred thirty-six healthy adults participated in the study. We found that
      TOI measurements of heart rate and heart rate variability (HRV), which reflects
      basal stress, corresponded strongly to those obtained from BIOPAC. These findings
      indicate that TOI technology is a viable method to monitor heart rate and HRV not
      only accurately but also conveniently, contactlessly, and remotely. Further,
      measures of HRV obtained via TOI serves as a valid index of basal stress.
      Potential applications of this technology in psychological research and other
      fields are discussed.

PMID- 29472881
TI  - Conditional Mediation of Absorptive Capacity and Environment in International
      Entrepreneurial Orientation of Family Businesses.
AB  - This study analyzes the effect of conditional mediation of environment-absorptive
      capacity in international entrepreneurial orientation of family businesses.
      Results involve data from 218 Spanish family businesses, analyzed with SmartPLS
      3.2.7 software. This paper presents a relevant contribution both to the academic
      field and the performance of family firms, helping to understand the process of
      transforming international entrepreneurial orientation into a better
      international performance through absorptive capacity while family businesses
      invest their efforts in aligning international entrepreneurial orientation and
      absorptive capacity with international results, bearing in mind the positive
      moderator effect of environment. The most relevant contribution of this work is
      to integrate in the same model the mediating effect of the absorption capacity
      and the moderating effect of the environment: the effect of the international
      entrepreneurial orientation on the international performance of family businesses
      improves with the mediation of the absorptive capacity (the variability of
      international performance goes from 32.5 to 40.6%) and the moderation of the
      environment (to variability of international performance goes from 40.6 to
      45.3%).

PMID- 29472880
TI  - Chewing Stimulation Reduces Appetite Ratings and Attentional Bias toward Visual
      Food Stimuli in Healthy-Weight Individuals.
AB  - Based on the theory of incentive sensitization, the exposure to food stimuli
      sensitizes the brain's reward circuits and enhances attentional bias toward food.
      Therefore, reducing attentional bias to food could possibly be beneficial in
      preventing impulsive eating. The importance of chewing has been increasingly
      implicated as one of the methods for reducing appetite, however, no studies to
      investigate the effect of chewing on attentional bias to food. In this study, we
      investigated whether chewing stimulation (i.e., chewing tasteless gum) reduces
      attentional bias to food as well as an actual feeding (i.e., ingesting a
      standardized meal) does. We measured reaction time, gaze direction and gaze
      duration to assess attentional bias toward food images in pairs of food and non
      food images that were presented in a visual probe task (Experiment 1, n = 21)
      and/or eye-tracking task (Experiment 2, n = 20). We also measured appetite
      ratings using visual analog scale. In addition, we conducted a control study in
      which the same number of participants performed the identical tasks to
      Experiments 1 and 2, but the participants did not perform sham feeding with gum
      chewing/actual feeding between tasks and they took a rest. Two-way ANOVA revealed
      that after actual feeding, subjective ratings of hunger, preoccupation with food,
      and desire to eat significantly decreased, whereas fullness significantly
      increased. Sham feeding showed the same trends, but to a lesser degree. Results
      of the visual probe task in Experiment 1 showed that both sham feeding and actual
      feeding reduced reaction time bias significantly. Eye-tracking data showed that
      both sham and actual feeding resulted in significant reduction in gaze direction
      bias, indexing initial attentional orientation. Gaze duration bias was
      unaffected. In both control experiments, one-way ANOVAs showed no significant
      differences between immediately before and after the resting state for any of the
      appetite ratings, reaction time bias, gaze direction bias, or gaze duration bias.
      In conclusion, chewing stimulation reduced subjective appetite and attentional
      bias to food, particularly initial attentional orientation to food. These
      findings suggest that chewing stimulation, even without taste, odor, or
      ingestion, may affect reward circuits and help prevent impulsive eating.

PMID- 29472882
TI  - The Quiet Eye and Motor Expertise: Explaining the "Efficiency Paradox".
AB  - It has been consistently reported that experts show longer quiet eye (QE)
      durations when compared to near-experts and novices. However, this finding is
      rather paradoxical as motor expertise is characterized by an economization of
      motor-control processes rather than by a prolongation in response programming, a
      suggested explanatory mechanism of the QE phenomenon. Therefore, an inhibition
      hypothesis was proposed that suggests an inhibition of non-optimal task solutions
      over movement parametrization, which is particularly necessary in experts due to
      the great extent and high density of their experienced task-solution space. In
      the current study, the effect of the task-solution space' extension was tested by
      comparing the QE-duration gains in groups that trained a far-aiming task with a
      small number (low-extent) vs. a large number (high-extent) of task variants.
      After an extensive training period of more than 750 trials, both groups showed
      superior performance in post-test and retention test when compared to pretest and
      longer QE durations in post-test when compared to pretest. However, the QE
      durations dropped to baseline values at retention. Finally, the expected
      additional gain in QE duration for the high-extent group was not found and thus,
      the assumption of long QE durations due to an extended task-solution space was
      not confirmed. The findings were (by tendency) more in line with the density
      explanation of the inhibition hypothesis. This density argument suits research
      revealing a high specificity of motor skills in experts thus providing worthwhile
      options for future research on the paradoxical relation between the QE and motor
      expertise.

PMID- 29472883
TI  - Belief Shift or Only Facilitation: How Semantic Expectancy Affects Processing of
      Speech Degraded by Background Noise.
AB  - Individuals use semantic expectancy - applying conceptual and linguistic
      knowledge to speech input - to improve the accuracy and speed of language
      comprehension. This study tested how adults use semantic expectancy in quiet and
      in the presence of speech-shaped broadband noise at -7 and -12 dB signal-to-noise
      ratio. Twenty-four adults (22.1 +/- 3.6 years, mean +/-SD) were tested on a four
      alternative-forced-choice task whereby they listened to sentences and were
      instructed to select an image matching the sentence-final word. The semantic
      expectancy of the sentences was unrelated to (neutral), congruent with, or
      conflicting with the acoustic target. Congruent expectancy improved accuracy and
      conflicting expectancy decreased accuracy relative to neutral, consistent with a
      theory where expectancy shifts beliefs toward likely words and away from unlikely
      words. Additionally, there were no significant interactions of expectancy and
      noise level when analyzed in log-odds, supporting the predictions of ideal
      observer models of speech perception.

PMID- 29472884
TI  - Functional Strength Training and Movement Performance Therapy for Upper Limb
      Recovery Early Poststroke-Efficacy, Neural Correlates, Predictive Markers, and
      Cost-Effectiveness: FAST-INdiCATE Trial.
AB  - Background: Variation in physiological deficits underlying upper limb paresis
      after stroke could influence how people recover and to which physical therapy
      they best respond. Objectives: To determine whether functional strength training
      (FST) improves upper limb recovery more than movement performance therapy (MPT).
      To identify: (a) neural correlates of response and (b) whether pre-intervention
      neural characteristics predict response. Design: Explanatory investigations
      within a randomised, controlled, observer-blind, and multicentre trial.
      Randomisation was computer-generated and concealed by an independent facility
      until baseline measures were completed. Primary time point was outcome, after the
      6-week intervention phase. Follow-up was at 6 months after stroke. Participants:
      With some voluntary muscle contraction in the paretic upper limb, not full
      dexterity, when recruited up to 60 days after an anterior cerebral circulation
      territory stroke. Interventions: Conventional physical therapy (CPT) plus either
      MPT or FST for up to 90 min-a-day, 5 days-a-week for 6 weeks. FST was "hands-off"
      progressive resistive exercise cemented into functional task training. MPT was
      "hands-on" sensory/facilitation techniques for smooth and accurate movement.
      Outcomes: The primary efficacy measure was the Action Research Arm Test (ARAT).
      Neural measures: fractional anisotropy (FA) corpus callosum midline; asymmetry of
      corticospinal tracts FA; and resting motor threshold (RMT) of motor-evoked
      potentials. Analysis: Covariance models tested ARAT change from baseline. At
      outcome: correlation coefficients assessed relationship between change in ARAT
      and neural measures; an interaction term assessed whether baseline neural
      characteristics predicted response. Results: 288 Participants had: mean age of
      72.2 (SD 12.5) years and mean ARAT 25.5 (18.2). For 240 participants with ARAT at
      baseline and outcome the mean change was 9.70 (11.72) for FST + CPT and 7.90
      (9.18) for MPT + CPT, which did not differ statistically (p = 0.298).
      Correlations between ARAT change scores and baseline neural values were between
      0.199, p = 0.320 for MPT + CPT RMT (n = 27) and -0.147, p = 0.385 for asymmetry
      of corticospinal tracts FA (n = 37). Interaction effects between neural values
      and ARAT change between baseline and outcome were not statistically significant.
      Conclusions: There was no significant difference in upper limb improvement
      between FST and MPT. Baseline neural measures did not correlate with upper limb
      recovery or predict therapy response. Trial registration: Current Controlled
      Trials: ISRCT 19090862, http://www.controlled-trials.com.

PMID- 29472886
TI  - Changes in Brain Lateralization in Patients with Mild Cognitive Impairment and
      Alzheimer's Disease: A Resting-State Functional Magnetic Resonance Study from
      Alzheimer's Disease Neuroimaging Initiative.
AB  - Purpose: To detect changes in brain lateralization in patients with mild
      cognitive impairment (MCI) and Alzheimer's disease (AD) using resting-state
      functional magnetic resonance imaging (fMRI). Materials and methods: Data from 61
      well-matched right-handed subjects were obtained from the Alzheimer's Disease
      Neuroimaging Initiative, including 19 healthy controls (HCs), 25 patients with
      MCI, and 17 patients with AD. First, we divided 256 pairs of seed regions from
      each hemisphere covering the entire cerebral gray matter. Then, we used the
      intrinsic laterality index (iLI) approach to quantify the functional laterality
      using fMRI. One-way ANOVA was employed to estimate the differences in iLI among
      the three groups. The sum, number and mean value of the iLI were calculated
      within the thresholds of 0 < |iLI| < 0.2, 0.2 <= |iLI| < 0.4, 0.4 <= |iLI| < 0.8,
      and |iLI| >= 0.8, to explore the changes in the lateralization of resting-state
      brain function in patients with MCI and AD. Results: One-way ANOVA revealed that
      the iLIs of the three groups were significantly different. The HCs showed a
      significant leftward interhemispheric difference within |iLI| >= 0.8. Compared
      with the HCs, the patients with MCI manifested a distinct abnormal rightward
      interhemispheric asymmetry, mainly within the thresholds of 0.2 <= |iLI| < 0.4
      and 0.4 <= |iLI| < 0.8; in the patients with AD, the normal leftward
      lateralization that was observed in the HCs disappeared, and an abnormal
      rightward laterality was expressed within 0.4 <= |iLI| < 0.8. By directly
      comparing the patients with MCI with the patients with AD, an exclusive abnormal
      rightward laterality was observed in the patients with MCI within the 0.2 <=
      |iLI| < 0.4 threshold, and the normal leftward asymmetry vanished in the patients
      with AD within the |iLI| >= 0.8 threshold. Conclusion: Global brain
      lateralization was different among three groups. The abnormal rightward dominance
      observed in the patients with MCI and AD may indicate that these patients use
      additional brain resources to compensate for the loss of cognitive function, and
      the observed disappearance of the leftward laterality in the patients with AD was
      likely associated with the damage in the left hemisphere. The observed
      disappearance of the rightward asymmetry in the patients with AD using the 0.2 <=
      |iLI| < 0.4 threshold was likely a sign of decompensation. Our study provides new
      insights that may improve our understanding of MCI and AD.

PMID- 29472887
TI  - A Possible Role for Platelet-Activating Factor Receptor in Amyotrophic Lateral
      Sclerosis Treatment.
AB  - Amyotrophic lateral sclerosis (ALS) is the third most prevalent neurodegenerative
      disease affecting upper and lower motor neurons. An important pathway that may
      lead to motor neuron degeneration is neuroinflammation. Cerebrospinal Fluids of
      ALS patients have increased levels of the inflammatory cytokine IL-18. Because IL
      18 is produced by dendritic cells stimulated by the platelet-activating factor
      (PAF), a major neuroinflammatory mediator, it is expected that PAF is involved in
      ALS. Here we show pilot experimental data on amplification of PAF receptor (PAFR)
      mRNA by RT-PCR. PAFR is overexpressed, as compared to age matched controls, in
      the spinal cords of transgenic ALS SOD1-G93A mice, suggesting PAF mediation.
      Although anti-inflammatory drugs have been tested for ALS before, no clinical
      trial has been conducted using PAFR specific inhibitors. Therefore, we
      hypothesize that administration of PAFR inhibitors, such as Ginkgolide B, PCA
      4248 and WEB 2086, have potential to function as a novel therapy for ALS,
      particularly in SOD1 familial ALS forms. Because currently there are only two
      approved drugs with modest effectiveness for ALS therapy, a search for novel
      drugs and targets is essential.

PMID- 29472888
TI  - The Effect of Visual Stimuli on Stability and Complexity of Postural Control.
AB  - Visual input could benefit balance control or increase postural sway, and it is
      far from fully understanding the effect of visual stimuli on postural stability
      and its underlying mechanism. In this study, the effect of different visual
      inputs on stability and complexity of postural control was examined by analyzing
      the mean velocity (MV), SD, and fuzzy approximate entropy (fApEn) of the center
      of pressure (COP) signal during quiet upright standing. We designed five visual
      exposure conditions: eyes-closed, eyes-open (EO), and three virtual reality (VR)
      scenes (VR1-VR3). The VR scenes were a limited field view of an optokinetic drum
      rotating around yaw (VR1), pitch (VR2), and roll (VR3) axes, respectively.
      Sixteen healthy subjects were involved in the experiment, and their COP
      trajectories were assessed from the force plate data. MV, SD, and fApEn of the
      COP in anterior-posterior (AP), medial-lateral (ML) directions were calculated.
      Two-way analysis of variance with repeated measures was conducted to test the
      statistical significance. We found that all the three parameters obtained the
      lowest values in the EO condition, and highest in the VR3 condition. We also
      found that the active neuromuscular intervention, indicated by fApEn, in response
      to changing the visual exposure conditions were more adaptive in AP direction,
      and the stability, indicated by SD, in ML direction reflected the changes of
      visual scenes. MV was found to capture both instability and active neuromuscular
      control dynamics. It seemed that the three parameters provided compensatory
      information about the postural control in the immersive virtual environment.

PMID- 29472885
TI  - The Pathoconnectivity Profile of Alzheimer's Disease: A Morphometric Coalteration
      Network Analysis.
AB  - Gray matter alterations are typical features of brain disorders. However, they do
      not impact on the brain randomly. Indeed, it has been suggested that
      neuropathological processes can selectively affect certain assemblies of neurons,
      which typically are at the center of crucial functional networks. Because of
      their topological centrality, these areas form a core set that is more likely to
      be affected by neuropathological processes. In order to identify and study the
      pattern formed by brain alterations in patients' with Alzheimer's disease (AD),
      we devised an innovative meta-analytic method for analyzing voxel-based
      morphometry data. This methodology enabled us to discover that in AD gray matter
      alterations do not occur randomly across the brain but, on the contrary, follow
      identifiable patterns of distribution. This alteration pattern exhibits a network
      like structure composed of coaltered areas that can be defined as coatrophy
      network. Within the coatrophy network of AD, we were able to further identify a
      core subnetwork of coaltered areas that includes the left hippocampus, left and
      right amygdalae, right parahippocampal gyrus, and right temporal inferior gyrus.
      In virtue of their network centrality, these brain areas can be thought of as
      pathoconnectivity hubs.

PMID- 29472889
TI  - Clinical and Magnetic Resonance Imaging Findings of Neurotoxocariasis.
AB  - Human toxocariasis is one of the most prevalent helminthiases worldwide. Toxocara
      canis larvae can cross the blood-brain barrier leading to the neurotoxocariasis.
      The clinical presentation consists of a wide spectrum of neurological
      manifestations, but asymptomatic infection is probably common. Neurotoxocariasis
      is not a frequent diagnosis probably due to the non-specific nature of its
      symptoms as well as the lack of confirmatory diagnostic tests. Diagnosis of
      neurotoxocariasis is based on the presence of a high titer of anti-Toxocara
      antibody in the cerebrospinal fluid or in the serum, presence of eosinophilia in
      the serum or cerebrospinal fluid, and clinical and radiological improvement after
      anthelmintic therapy; however, universally accepted diagnostic criteria are
      lacking. Magnetic resonance imaging (MRI) findings include single or multiple,
      subcortical, cortical or white matter hyperintense lesions, best visualized on
      FLAIR and T2-weighted imaging, and usually isointense or hypointense on T1. These
      imaging findings are suggestive but not specific to neurotoxocariasis. Definitive
      diagnosis is made by histological confirmation, but it is rarely followed. This
      review provides an overview of the clinical manifestations, management options,
      and MRI findings of neurotoxocariasis.

PMID- 29472890
TI  - Severe Blood-Brain Barrier Disruption in Cardioembolic Stroke.
AB  - Background: Previous studies demonstrated that cardioembolism (CE) was prone to
      develop hemorrhagic transformation (HT), whereas hyper-permeability of blood
      brain barrier (BBB) might be one reason for the development of HT. We, thus,
      aimed to investigate whether the BBB permeability (BBBP) was higher in CE stroke
      than other stroke subtypes in acute ischemic stroke (AIS) patients. Methods: This
      study was a retrospective review of prospectively collected clinical and imaging
      database of AIS patients who underwent CT perfusion. Hypoperfusion was defined as
      Tmax >6 s. The average relative permeability-surface area product (rPS),
      reflecting the BBBP, was calculated within the hypoperfusion region (rPShypo). CE
      was diagnosed according to the international Trial of Org 10172 in Acute Stroke
      Treatment criteria. Receiver operating characteristics (ROC) curve analysis was
      used to determine predictive value of rPShypo for CE. Logistic regression was
      used to identify independent predictors for CE. Results: A total of 187 patients
      were included in the final analysis [median age, 73 (61-80) years; 75 (40.1%)
      females; median baseline National Institutes of Health Stroke Scale score, 12 (7
      16)]. Median rPShypo was 65.5 (35.8-110.1)%. Ninety-seven (51.9%) patients were
      diagnosed as CE. ROC analysis revealed that the optimal rPShypo threshold for CE
      was 86.71%. The value of rPShypo and the rate of rPShypo>86.71% were
      significantly higher in patients with CE than other stroke subtypes (p < 0.05),
      after adjusting for the potential confounds. Conclusion: The extent of BBB
      disruption is more severe in CE stroke than other stroke subtypes during the
      hyperacute stage.

PMID- 29472891
TI  - A Review of Traumatic Axonal Injury following Whiplash Injury As Demonstrated by
      Diffusion Tensor Tractography.
AB  - Whiplash is a bony or soft tissue injury resulting from an acceleration
      deceleration energy transfer in the neck. Although patients with whiplash injury
      often complain of cerebral symptoms, and previous studies have reported evidence
      indicating brain injury, such an association has not been clearly elucidated.
      Traumatic axonal injury (TAI) is tearing of axons due to indirect shearing forces
      during acceleration, deceleration, and rotation of the brain or to direct head
      trauma. Diffusion tensor imaging (DTI) has a unique advantage to detect TAI in
      patients whose conventional brain CT or magnetic resonance imaging (MRI) results
      were negative following head trauma. Since the introduction of DTI, six studies
      using diffusion tensor tractography (DTT) based on DTI data have reported TAI in
      patients with whiplash injury, even though conventional brain CT or MRI results
      were negative. A precise TAI diagnosis in whiplash patients is clinically
      important for proper management and prognosis. Among the methods employed to
      diagnose TAI in the six previous studies, the common diagnostic approach for
      neural tract TAI in individual patients with whiplash injury were (1) whiplash
      injury history due to car accident; (2) development of new clinical symptoms and
      signs after whiplash injury; (3) evidence of neural tract TAI in DTT results,
      mainly via configurational analysis; and (4) coincidence of newly developed
      clinical manifestations and the function of injured neural tracts. All six
      studies were individual patient case studies; therefore, further prospective
      studies involving larger number of subjects should be encouraged.

PMID- 29472892
TI  - Maternal and Cord Blood Vitamin D Status and Anthropometric Measurements in Term
      Newborns at Birth.
AB  - Introduction: Vitamin D deficiency in pregnant women may result in reduced
      neonatal development due to the fact that systemic vitamin D status during fetal
      life depends on maternal concentrations. Some authors reported significant
      differences in neonatal anthropometric measurements depending on maternal vitamin
      D concentrations. Objective: The aim of this study is to evaluate the
      relationship between maternal and cord blood concentrations of vitamin D and
      neonatal anthropometric measurements at birth. Materials and methods: This study
      included 94 pregnant women, at term, who delivered at the Department of
      Obstetrics, Women's Diseases and Gynecological Oncology, Medical University of
      Warsaw. Total serum 25(OH)D concentration was measured in mother-child pairs, and
      newborn anthropometric data were collected. A multiple regression analysis was
      used for statistical analysis. Results: No relationship between maternal and
      neonatal cord blood vitamin D concentrations vs. neonatal weight, length, head,
      and chest circumference at birth was found (p > 0.05). Severe vitamin D
      deficiency (<10 ng/ml) was detected in 10.6%, deficiency (10-20 ng/ml) in 39.4%,
      insufficiency (20-30 ng/ml) in 39.4%, and optimal vitamin D concentration (>30
      ng/ml) only in 10.6% of the pregnant women. Cord blood vitamin D deficiency (<20
      ng/ml) was found in 28.7% of the neonates. Conclusion: No differences between
      neonatal anthropometric measurements of infants born to mothers with normal and
      deficient vitamin D concentrations were found.

PMID- 29472894
TI  - Photosynthesis Is Widely Distributed among Proteobacteria as Demonstrated by the
      Phylogeny of PufLM Reaction Center Proteins.
AB  - Two different photosystems for performing bacteriochlorophyll-mediated
      photosynthetic energy conversion are employed in different bacterial phyla. Those
      bacteria employing a photosystem II type of photosynthetic apparatus include the
      phototrophic purple bacteria (Proteobacteria), Gemmatimonas and Chloroflexus with
      their photosynthetic relatives. The proteins of the photosynthetic reaction
      center PufL and PufM are essential components and are common to all bacteria with
      a type-II photosynthetic apparatus, including the anaerobic as well as the
      aerobic phototrophic Proteobacteria. Therefore, PufL and PufM proteins and their
      genes are perfect tools to evaluate the phylogeny of the photosynthetic apparatus
      and to study the diversity of the bacteria employing this photosystem in nature.
      Almost complete pufLM gene sequences and the derived protein sequences from 152
      type strains and 45 additional strains of phototrophic Proteobacteria employing
      photosystem II were compared. The results give interesting and comprehensive
      insights into the phylogeny of the photosynthetic apparatus and clearly define
      Chromatiales, Rhodobacterales, Sphingomonadales as major groups distinct from
      other Alphaproteobacteria, from Betaproteobacteria and from Caulobacterales
      (Brevundimonas subvibrioides). A special relationship exists between the PufLM
      sequences of those bacteria employing bacteriochlorophyll b instead of
      bacteriochlorophyll a. A clear phylogenetic association of aerobic phototrophic
      purple bacteria to anaerobic purple bacteria according to their PufLM sequences
      is demonstrated indicating multiple evolutionary lines from anaerobic to aerobic
      phototrophic purple bacteria. The impact of pufLM gene sequences for studies on
      the environmental diversity of phototrophic bacteria is discussed and the
      possibility of their identification on the species level in environmental samples
      is pointed out.

PMID- 29472893
TI  - Late-Onset Puberty Induction by Transdermal Estrogen in Turner Syndrome Girls-A
      Longitudinal Study.
AB  - Objective: Estrogen replacement therapy (ERT) for Turner syndrome (TS) is a
      widely discussed topic; however, the optimal model of ERT for patients with
      delayed diagnosis and/or initiation of therapy is still unclear, mainly due to
      insufficient data. We present the results of a prospective observational single
      center study in which the efficacy of late-onset puberty induction by one-regimen
      transdermal ERT in TS girls was evaluated. Methods: The analysis encompassed 49
      TS girls (63.3% with 45,X) with hypergonadotropic hypogonadism in whom unified
      transdermal ERT protocol was used for puberty induction (first two months 12.5
      MUg/24 h, thereafter 25.0 MUg/24 h until breakthrough bleeding). Clinical visits
      for examination and therapy modification took place every 3-6 months.
      Transabdominal pelvic ultrasound examinations were performed at least twice: at
      the beginning and at the end of follow-up. Results: The mean (SD) age at ERT
      induction was 15.1 (1.3) years. The duration of follow-up was 2.4 (1.1) years.
      Half of all the patients had at least B2 after 0.57 years, B3 after 1.1 years, B4
      after 1.97 years, and menarche after 1.82 years from ERT initiation. With earlier
      initiation of ERT (<=14 years), B2 (p = 0.059) was achieved faster and B4 (p =
      0.018) significantly slower than with the later start of ERT. Thirty-four (94.4%)
      patients had at least stage B3 at menarche. The karyotype, initial weight, and
      body mass index had no impact on puberty tempo during ERT. The uterine volume
      increased significantly during ERT in all the study group (p < 0.0001), and in
      half of the patients, the increase was at least 12.4-fold. It did not correlate
      with the duration of treatment (p = 0.84) or the dose of estradiol per kilogram
      (p = 0.78), nor did it depend on karyotype (p = 0.71) or age at ERT initiation (p
      = 0.28). There were no differences in DeltahSDS during ERT (p = 0.63) between the
      two age groups (ERT <=14 and >14 years). Conclusion: The presented easy-to-use
      fixed-dose regimen for late-onset puberty induction allowed for a satisfactory
      rate of achieving subsequent puberty stages and did not influence the growth
      potential.

PMID- 29472895
TI  - Bile-Salt-Hydrolases from the Probiotic Strain Lactobacillus johnsonii La1
      Mediate Anti-giardial Activity in Vitro and in Vivo.
AB  - Giardia duodenalis (syn. G. lamblia, G. intestinalis) is the protozoan parasite
      responsible for giardiasis, the most common and widely spread intestinal
      parasitic disease worldwide, affecting both humans and animals. After cysts
      ingestion (through either contaminated food or water), Giardia excysts in the
      upper intestinal tract to release replicating trophozoites that are responsible
      for the production of symptoms. In the gut, Giardia cohabits with the host's
      microbiota, and several studies have revealed the importance of this gut
      ecosystem and/or some probiotic bacteria in providing protection against G.
      duodenalis infection through mechanisms that remain incompletely understood.
      Recent findings suggest that Bile-Salt-Hydrolase (BSH)-like activities from the
      probiotic strain of Lactobacillus johnsonii La1 may contribute to the anti
      giardial activity displayed by this strain. Here, we cloned and expressed each of
      the three bsh genes present in the L. johnsonii La1 genome to study their
      enzymatic and biological properties. While BSH47 and BSH56 were expressed as
      recombinant active enzymes, no significant enzymatic activity was detected with
      BSH12. In vitro assays allowed determining the substrate specificities of both
      BSH47 and BSH56, which were different. Modeling of these BSHs indicated a strong
      conservation of their 3-D structures despite low conservation of their primary
      structures. Both recombinant enzymes were able to mediate anti-giardial
      biological activity against Giardia trophozoites in vitro. Moreover, BSH47
      exerted significant anti-giardial effects when tested in a murine model of
      giardiasis. These results shed new light on the mechanism, whereby active BSH
      derived from the probiotic strain Lactobacillus johnsonii La1 may yield anti
      giardial effects in vitro and in vivo. These findings pave the way toward novel
      approaches for the treatment of this widely spread but neglected infectious
      disease, both in human and in veterinary medicine.

PMID- 29472896
TI  - Bacterial Therapy of Cancer: Promises, Limitations, and Insights for Future
      Directions.
AB  - Spontaneous tumors regression has been associated with microbial infection for
      100s of years and inspired the use of bacteria for anticancer therapy. Dr.
      William B. Coley (1862-1936), a bone- sarcoma surgeon, was a pioneer in treating
      his patients with both live bacterial-based and mixture of heat-killed bacteria
      known as "Coley's toxins." Unfortunately, Coley was forced to stop his work which
      interrupted this field for about half a century. Currently, several species of
      bacteria are being developed against cancer. The bacterial species, their genetic
      background and their infectious behavior within the tumor microenvironment are
      thought to be relevant factors in determining their anti-tumor effectiveness in
      vivo. In this perspective article we will update the most promising results
      achieved using bacterial therapy (alone or combined with other strategies) in
      clinically-relevant animal models of cancer and critically discuss the impact of
      the bacterial variants, route of administration and mechanisms of bacteria-cancer
      cell interaction. We will also discuss strategies to apply this information using
      modern mouse models, molecular biology, genetics and imaging for future bacterial
      therapy of cancer patients.

PMID- 29472897
TI  - Microbial Community Structure and Function Indicate the Severity of Chromium
      Contamination of the Yellow River.
AB  - The Yellow River is the most important water resource in northern China. In the
      recent past, heavy metal contamination has become severe due to industrial
      processes and other anthropogenic activities. In this study, riparian soil
      samples with varying levels of chromium (Cr) pollution severity were collected
      along the Gansu industrial reach of the Yellow River, including samples from
      uncontaminated sites (XC, XGU), slightly contaminated sites (LJX, XGD), and
      heavily contaminated sites (CG, XG). The Cr concentrations of these samples
      varied from 83.83 mg?kg-1 (XGU) to 506.58 mg?kg-1 (XG). The chromate [Cr (VI)]
      reducing ability in the soils collected in this study followed the sequence of
      the heavily contaminated > slightly contaminated > the un-contaminated. Common Cr
      remediation genes chrA and yieF were detected in the XG and CG samples. qRT-PCR
      results showed that the expression of chrA was up-regulated four and threefold in
      XG and CG samples, respectively, whereas the expression of yieF was up-regulated
      66- and 7-fold in the same samples after 30 min treatment with Cr (VI). The copy
      numbers of chrA and yieF didn't change after 35 days incubation with Cr (VI). The
      microbial communities in the Cr contaminated sampling sites were different from
      those in the uncontaminated samples. Especially, the relative abundances of
      Firmicutes and Bacteroidetes were higher while Actinobacteria was lower in the
      contaminated group than uncontaminated group. Further, potential indicator
      species, related to Cr such as Cr-remediation genera (Geobacter, PSB-M-3,
      Flavobacterium, and Methanosarcina); the Cr-sensitive genera (Skermanella, Iamia,
      Arthrobacter, and Candidatus Nitrososphaera) were also identified. These data
      revealed that Cr shifted microbial composition and function. Further, Cr (VI)
      reducing ability could be related with the expression of Cr remediation genes.

PMID- 29472898
TI  - Microbial Diversity and Mineralogical-Mechanical Properties of Calcitic Cave
      Speleothems in Natural and in Vitro Biomineralization Conditions.
AB  - Natural mineral formations are a window into important processes leading to
      carbon storage and mineralized carbonate structures formed through abiotic and
      biotic processes. In the current study, we made an attempt to undertake a
      comprehensive approach to characterize the mineralogical, mechanical, and
      microbial properties of different kinds of speleothems from karstic caves; with
      an aim to understand the bio-geo-chemical processes in speleothem structures and
      their impact on nanomechanical properties. We also investigated the
      biomineralization abilities of speleothem surface associated microbial
      communities in vitro. Mineralogical profiling using techniques such as X-ray
      powder Diffraction (XRD) and Tescan Integrated Mineral Analyzer (TIMA)
      demonstrated that calcite was the dominant mineral in the majority of speleothems
      with Energy Dispersive X-ray Analysis (EDS) indicating a few variations in the
      elemental components. Differing proportions of polymorphs of calcium carbonate
      such as aragonite and vaterite were also recorded. Significant variations in
      trace metal content were recorded through Inductively Coupled Plasma Mass
      Spectrometer (ICP-MS). Scanning Electron Microscopy (SEM) analysis revealed
      differences in morphological features of the crystals which varied from
      triangular prismatic shapes to etched spiky forms. Microbial imprints and
      associations were seen in a few sections. Analysis of the associated microbial
      diversity showed significant differences between various speleothems at Phylum
      level; although Proteobacteria and Actinobacteria were found to be the
      predominant groups. Genus level microbial associations showed a relationship with
      the geochemistry, mineralogical composition, and metal content of the
      speleothems. The assessment of nanomechanical properties measured by
      Nanoindentation revealed that the speleothems with a dominance of calcite were
      stronger than the speleothems with mixed calcium carbonate polymorphs and silica
      content. The in vitro metabolic activity of the microbial communities associated
      with the surfaces of the speleothems resulted in calcium carbonate crystal
      precipitation. Firmicutes and Proteobacteria dominated these populations, in
      contrast to the populations seen in natural systems. The precipitation of calcium
      carbonate crystals in vitro indicated that microbial metabolic activity may also
      play an important role in the synthesis and dissociation of biominerals in the
      natural environment. Our study provides novel evidence of the close relationship
      between mineralogy, microbial ecology, geochemistry, and nanomechanical
      properties of natural formations.

PMID- 29472899
TI  - Exposure to Sub-lethal 2,4-Dichlorophenoxyacetic Acid Arrests Cell Division and
      Alters Cell Surface Properties in Escherichia coli.
AB  - Escherichia coli is a robust, easily adaptable and culturable bacterium in vitro,
      and a model bacterium for studying the impact of xenobiotics in the environment.
      We have used correlative atomic force - laser scanning confocal microscopy (AFM
      LSCM) to characterize the mechanisms of cellular response to the herbicide 2,4
      dichlorophenoxyacetic acid (2,4-D). One of the most extensively used herbicides
      world-wide, 2,4-D is known to cause hazardous effects in diverse non-target
      organisms. Sub-lethal concentrations of 2,4-D caused DNA damage in E. coli WM1074
      during short exposure periods which increased significantly over time. In
      response to 2,4-D, FtsZ and FtsA relocalized within seconds, coinciding with the
      complete inhibition of cell septation and cell elongation. Exposure to 2,4-D also
      resulted in increased activation of the SOS response. Changes to cell division
      were accompanied by concomitant changes to surface roughness, elasticity and
      adhesion in a time-dependent manner. This is the first study describing the
      mechanistic details of 2,4-D at sub-lethal levels in bacteria. Our study suggests
      that 2,4-D arrests E. coli cell division within seconds after exposure by
      disrupting the divisome complex, facilitated by dissipation of membrane
      potential. Over longer exposures, 2,4-D causes filamentation as a result of an
      SOS response to oxidative stress induced DNA damage.

PMID- 29472900
TI  - Spatial Heterogeneity and Co-occurrence of Mucosal and Luminal Microbiome across
      Swine Intestinal Tract.
AB  - Pigs are one of the most important economic livestock. Gut microbiota is not only
      critical to the health but also the production efficiency of pigs. Manipulating
      gut microbiota relies on the full view of gut microbiome and the understanding of
      drive forces shaping microbial communities. 16s rDNA sequencing was used to
      profile microbiota along the longitudinal and radical axes to obtain the
      topographical map of microbiome in different intestinal compartments in young
      pigs. Alpha and beta-diversities revealed distinct differences in microbial
      compositions between the distal ileum and cecum and colon, as well as between the
      lumen and mucosa. Firmicutes and Proteobacteria dominated in the ileum,
      constituting 95 and 80% of the luminal and mucosa-attached microbiome.
      Transitioning from the small intestine to the large intestine, luminal
      Bacteroidetes increased from 1.69 to 45.98% in the cecum and 40.09% in the colon,
      while mucosal Bacteroidetes raised from 9 to 35.36% and 27.96%. Concurrently,
      luminal Firmicutes and Proteobacteria and mucosal-attached Proteobacteria
      remarkably decreased. By co-occurrence network analyses, Prevotellaceae,
      Ruminococcaceae, Lachnospiraceae and Veillonellaceae were recognized as the
      central nodes of luminal microbial network, and Prevotellaceae and
      Enterobacteriaceae, Caulobacteraceae, Enterococcaceae, Xanthomonadaceae,
      Pseudomonadaceae were identified as mucosal central nodes. Co-abundance was
      uncovered among Prevotellaceae, Lachnospiraceae, and Veillonellaceae in the
      luminal and mucosal microbiome, while opportunistic pathogens from gamma
      Proteobacteria in the mucosa. Strong co-exclusion was shown between
      Enterobacteriaceae with Prevotellaceae-centered microbial groups in the lumen.
      Redundancy analysis found bile acids and short chain fatty acids explained 37.1
      and 41% of variations in the luminal microbial composition, respectively. Primary
      bile acid, taurine- and glycine- conjugated bile acids were positively correlated
      with Lactobacillaceae, Enterobacteriaceae, Clostridiaceae_1,
      Peptostreptococcaceae, whereas secondary bile acids, acetate, propionate,
      butyrate, and valerate were positively correlated with Prevotellaceae,
      Acidaminococcaceae, Ruminococcaceae, Lachnospiraceae, Desulfovibronaceae,
      Veillonellaceae. Functional analyses demonstrated that Prevotella,
      Veillonellaceae, Lachnospiraceae, and Ruminococcaceae were positively correlated
      with gene functions related to amino acids, energy, cofactors and vitamins
      metabolism, which are indispensable for the hosts. These results suggested site
      specific colonization and co-occurrence of swine gut microbiome closely relate to
      the microenvironment in each niche. Interactions of core gut microbiome greatly
      contributed to metabolism and/or immunity in the swine intestine.

PMID- 29472901
TI  - New Aspects on Listeria monocytogenes ST5-ECVI Predominance in a Heavily
      Contaminated Cheese Processing Environment.
AB  - The eradication of Listeria monocytogenes from food chains is still a great
      challenge for the food industry and control authorities since some clonal
      complexes (CCs) are either better adapted to food processing environments (FPEs)
      or are globally widespread. In this work, we focus on the in-house evolution of
      L. monocytogenes genotypes collected from a heavily contaminated FPE whose
      contamination pattern underwent a massive and yet unexplained change. At the
      beginning of the sampling in 2010, a high variety of most likely transient L.
      monocytogenes genotypes was detected belonging to sequence type (ST) 1, ST7,
      ST21, ST37. After several efforts to intensify the hygiene measures, the
      variability was reduced to L. monocytogenes ST5 that was dominant in the
      following years 2011 and 2012. We aimed to elucidate possible genetic mechanisms
      responsible for the high abundance and persistence of ST5 strains in this FPE.
      Therefore, we compared the genomes of six L. monocytogenes ST5 strains to the
      less frequently occurring transient L. monocytogenes ST37 and ST204 from the same
      FPE as well as the highly abundant ST1 and ST21 isolated in 2010. Whole genome
      analysis indicated a high degree of conservation among ST5 strains [average
      nucleotide identity (ANI) 99.93-99.99%; tetranucleotide correlation 0.99998
      0.99999]. Slight differences in pulsed field gel electrophoresis (PFGE) patterns
      of two ST5 isolates could be explained by genetic changes in the tRNA-Arg-TCT
      prophages. ST5 and ST204 strains harbored virtually identical 91 kbp plasmids
      related to plasmid group 2 (pLM80 and pLMUCDL175). Interestingly, highly abundant
      genotypes present in the FPE in 2010 did not harbor any plasmids. The ST5
      plasmids harbored an efflux pump system (bcrABC cassette) and heavy metal
      resistance genes possibly providing a higher tolerance to disinfectants. The
      pLM80 prototype plasmids most likely provide important genetic determinants for a
      better survival of L. monocytogenes in the FPE. We reveal short-term evolution of
      L. monocytogenes strains within the same FPE over a 3 year period and our results
      suggest that plasmids are important for the persistence of ST5 strains in this
      FPE.

PMID- 29472903
TI  - Bile Salt Hydrolase Activities: A Novel Target to Screen Anti-Giardia
      Lactobacilli?
AB  - Giardia duodenalis is a protozoan parasite responsible for giardiasis, a disease
      characterized by intestinal malabsorption, diarrhea and abdominal pain in a large
      number of mammal species. Giardiasis is one of the most common intestinal
      parasitic diseases in the world and thus a high veterinary, and public health
      concern. It is well-established that some probiotic bacteria may confer
      protection against this parasite in vitro and in vivo and we recently documented
      the implication of bile-salt hydrolase (BSH)-like activities from strain La1 of
      Lactobacillus johnsonii as mediators of these effects in vitro. We showed that
      these activities were able to generate deconjugated bile salts that were toxic to
      the parasite. In the present study, a wide collection of lactobacilli strains
      from different ecological origins was screened to assay their anti-giardial
      effects. Our results revealed that the anti-parasitic effects of some of the
      strains tested were well-correlated with the expression of BSH-like activities.
      The two most active strains in vitro, La1 and Lactobacillus gasseri CNCM I-4884,
      were then tested for their capacity to influence G. duodenalis infection in a
      suckling mice model. Strikingly, only L. gasseri CNCM I-4884 strain was able to
      significantly antagonize parasite growth with a dramatic reduction of the
      trophozoites load in the small intestine. Moreover, this strain also
      significantly reduced the fecal excretion of Giardia cysts after 5 days of
      treatment, which could contribute to blocking the transmission of the parasite,
      in contrast of La1 where no effect was observed. This study represents a step
      toward the development of new prophylactic strategies to combat G. duodenalis
      infection in both humans and animals.

PMID- 29472904
TI  - Metabolic and Genetic Properties of Petriella setifera Precultured on Waste.
AB  - Although fungi that belong to Petriella genus are considered to be favorable
      agents in the process of microbial decomposition or as plant endophytes, they may
      simultaneously become plant pests. Hence, nutrition factors are supposed to play
      an important role. Therefore, it was hypothesized that Petriella setifera compost
      isolates, precultured on three different waste-based media containing oak
      sawdust, beet pulp (BP) and wheat bran (WB) will subsequently reveal different
      metabolic properties and shifts in genetic fingerprinting. In fact, the aim was
      to measure the influence of selected waste on the properties of P. setifera. The
      metabolic potential was evaluated by the ability of five P. setifera strains to
      decompose oak sawdust, BP and WB following the MT2 plate(r) method and the
      catabolic abilities of the fungus to utilize the carbon compounds located on
      filamentous fungi (FF) plates(r). Genetic diversity was evaluated using Amplified
      Fragment Length Polymorphism analysis performed both on DNA sequences and on
      transcript-derived fragments. P. setifera isolates were found to be more suitable
      for decomposing waste materials rich in protein, N, P, K and easily accessible
      sugars (as found in WB and BP), than those rich in lignocellulose (oak sawdust).
      Surprisingly, among the different waste media, lignocellulose-rich sawdust-based
      culture chiefly triggered changes in the metabolic and genetic features of P.
      setifera. Most particularly, it contributed to improvements in the ability of the
      fungus to utilize waste-substrates in MT2 plate(r) and two times increase the
      ability to catabolize carbon compounds located in FF plates(r). Expressive
      metabolic properties resulting from being grown in sawdust-based substrate were
      in accordance with differing genotype profiles but not transcriptome.
      Intraspecific differences among P. setifera isolates are described.

PMID- 29472902
TI  - Prevention and Control Strategies to Counter Zika Virus, a Special Focus on
      Intervention Approaches against Vector Mosquitoes-Current Updates.
AB  - Zika virus (ZIKV) is the most recent intruder that acquired the status of global
      threat creating panic and frightening situation to public owing to its rapid
      spread, attaining higher virulence and causing complex clinical manifestations
      including microcephaly in newborns and Guillain Barre Syndrome. Alike other
      flaviviruses, the principal mode of ZIKV transmission is by mosquitoes. Advances
      in research have provided reliable diagnostics for detecting ZIKV infection,
      while several drug/therapeutic targets and vaccine candidates have been
      identified recently. Despite these progresses, currently there is neither any
      effective drug nor any vaccine available against ZIKV. Under such circumstances
      and to tackle the problem at large, control measures of which mosquito population
      control need to be strengthened following appropriate mechanical, chemical,
      biological and genetic control measures. Apart from this, several other known
      modes of ZIKV transmission which have gained importance in recent past such as
      intrauterine, sexual intercourse, and blood-borne spread need to be checked and
      kept under control by adopting appropriate precautions and utmost care during
      sexual intercourse, blood transfusion and organ transplantation. The virus
      inactivation by pasteurization, detergents, chemicals, and filtration can
      effectively reduce viral load in plasma-derived medicinal products. Added to
      this, strengthening of the surveillance and monitoring of ZIKV as well as
      avoiding travel to Zika infected areas would aid in keeping viral infection under
      check. Here, we discuss the salient advances in the prevention and control
      strategies to combat ZIKV with a focus on highlighting various intervention
      approaches against the vector mosquitoes of this viral pathogen along with
      presenting an overview regarding human intervention measures to counter other
      modes of ZIKV transmission and spread. Additionally, owing to the success of
      vaccines for a number of infections globally, a separate section dealing with
      advances in ZIKV vaccines and transmission blocking vaccines has also been
      included.

PMID- 29472905
TI  - 1-((2,4-Dichlorophenethyl)Amino)-3-Phenoxypropan-2-ol Kills Pseudomonas
      aeruginosa through Extensive Membrane Damage.
AB  - The ever increasing multidrug-resistance of clinically important pathogens and
      the lack of novel antibiotics have resulted in a true antibiotic crisis where
      many antibiotics are no longer effective. Further complicating the treatment of
      bacterial infections are antibiotic-tolerant persister cells. Besides being
      responsible for the recalcitrant nature of chronic infections, persister cells
      greatly contribute to the observed antibiotic tolerance in biofilms and even
      facilitate the emergence of antibiotic resistance. Evidently, eradication of
      these persister cells could greatly improve patient outcomes and targeting
      persistence may provide an alternative approach in combatting chronic infections.
      We recently characterized 1-((2,4-dichlorophenethyl)amino)-3-phenoxypropan-2-ol
      (SPI009), a novel anti-persister molecule capable of directly killing persisters
      from both Gram-negative and Gram-positive pathogens. SPI009 potentiates
      antibiotic activity in several in vitro and in vivo infection models and
      possesses promising anti-biofilm activity. Strikingly, SPI009 restores antibiotic
      sensitivity even in resistant strains. In this study, we investigated the mode of
      action of this novel compound using several parallel approaches. Genetic analyses
      and a macromolecular synthesis assays suggest that SPI009 acts by causing
      extensive membrane damage. This hypothesis was confirmed by liposome leakage
      assay and membrane permeability studies, demonstrating that SPI009 rapidly
      impairs the bacterial outer and inner membranes. Evaluation of SPI009-resistant
      mutants, which only could be generated under severe selection pressure, suggested
      a possible role for the MexCD-OprJ efflux pump. Overall, our results demonstrate
      the extensive membrane-damaging activity of SPI009 and confirm its clinical
      potential in the development of novel anti-persister therapies.

PMID- 29472906
TI  - The DNA Methylome of the Hyperthermoacidophilic Crenarchaeon Sulfolobus
      acidocaldarius.
AB  - DNA methylation is the most common epigenetic modification observed in the
      genomic DNA (gDNA) of prokaryotes and eukaryotes. Methylated nucleobases, N6
      methyl-adenine (m6A), N4-methyl-cytosine (m4C), and 5-methyl-cytosine (m5C),
      detected on gDNA represent the discrimination mark between self and non-self DNA
      when they are part of restriction-modification systems in prokaryotes (Bacteria
      and Archaea). In addition, m5C in Eukaryotes and m6A in Bacteria play an
      important role in the regulation of key cellular processes. Although archaeal
      genomes present modified bases as in the two other domains of life, the
      significance of DNA methylations as regulatory mechanisms remains largely
      uncharacterized in Archaea. Here, we began by investigating the DNA methylome of
      Sulfolobus acidocaldarius. The strategy behind this initial study entailed the
      use of combined digestion assays, dot blots, and genome resequencing, which
      utilizes specific restriction enzymes, antibodies specifically raised against m6A
      and m5C and single-molecule real-time (SMRT) sequencing, respectively, to
      identify DNA methylations occurring in exponentially growing cells. The
      previously identified restriction-modification system, specific of S.
      acidocaldarius, was confirmed by digestion assay and SMRT sequencing while, the
      presence of m6A was revealed by dot blot and identified on the characteristic Dam
      motif by SMRT sequencing. No m5C was detected by dot blot under the conditions
      tested. Furthermore, by comparing the distribution of both detected methylations
      along the genome and, by analyzing DNA methylation profiles in synchronized
      cells, we investigated in which cellular pathways, in particular the cell cycle,
      this m6A methylation could be a key player. The analysis of sequencing data
      rejected a role for m6A methylation in another defense system and also raised new
      questions about a potential involvement of this modification in the regulation of
      other biological functions in S. acidocaldarius.

PMID- 29472907
TI  - Regulation of Effector Delivery by Type III Secretion Chaperone Proteins in
      Erwinia amylovora.
AB  - Type III secretion (TTS) chaperones are critical for the delivery of many
      effector proteins from Gram-negative bacterial pathogens into host cells,
      functioning in the stabilization and hierarchical delivery of the effectors to
      the type III secretion system (TTSS). The plant pathogen Erwinia amylovora
      secretes at least four TTS effector proteins: DspE, Eop1, Eop3, and Eop4. DspE
      specifically interacts with the TTS chaperone protein DspF, which stabilizes the
      effector protein in the cytoplasm and promotes its efficient translocation
      through the TTSS. However, the role of E. amylovora chaperones in regulating the
      delivery of other secreted effectors is unknown. In this study, we identified
      functional interactions between the effector proteins DspE, Eop1, and Eop3 with
      the TTS chaperones DspF, Esc1 and Esc3 in yeast. Using site-directed mutagenesis,
      secretion, and translocation assays, we demonstrated that the three TTS
      chaperones have additive roles for the secretion and translocation of DspE into
      plant cells whereas DspF negatively affects the translocation of Eop1 and Eop3.
      Collectively, these results indicate that TTS chaperone proteins exhibit a
      cooperative behavior to orchestrate the effector secretion and translocation
      dynamics in E. amylovora.

PMID- 29472909
TI  - Metagenomic Profiling of Soil Microbes to Mine Salt Stress Tolerance Genes.
AB  - Osmotolerance is one of the critical factors for successful survival and
      colonization of microbes in saline environments. Nonetheless, information about
      these osmotolerance mechanisms is still inadequate. Exploration of the saline
      soil microbiome for its community structure and novel genetic elements is likely
      to provide information on the mechanisms involved in osmoadaptation. The present
      study explores the saline soil microbiome for its native structure and novel
      genetic elements involved in osmoadaptation. 16S rRNA gene sequence analysis has
      indicated the dominance of halophilic/halotolerant phylotypes affiliated to
      Proteobacteria, Actinobacteria, Gemmatimonadetes, Bacteroidetes, Firmicutes, and
      Acidobacteria. A functional metagenomics approach led to the identification of
      osmotolerant clones SSR1, SSR4, SSR6, SSR2 harboring BCAA_ABCtp, GSDH, STK_Pknb,
      and duf3445 genes. Furthermore, transposon mutagenesis, genetic, physiological
      and functional studies in close association has confirmed the role of these genes
      in osmotolerance. Enhancement in host osmotolerance possibly though the cytosolic
      accumulation of amino acids, reducing equivalents and osmolytes involving BCAA
      ABCtp, GSDH, and STKc_PknB. Decoding of the genetic elements prevalent within
      these microbes can be exploited either as such for ameliorating soils or their
      genetically modified forms can assist crops to resist and survive in saline
      environment.

PMID- 29472908
TI  - Mining Halophytes for Plant Growth-Promoting Halotolerant Bacteria to Enhance the
      Salinity Tolerance of Non-halophytic Crops.
AB  - Salinity stress is one of the major abiotic stresses limiting crop production in
      arid and semi-arid regions. Interest is increasing in the application of PGPRs
      (plant growth promoting rhizobacteria) to ameliorate stresses such as salinity
      stress in crop production. The identification of salt-tolerant, or halophilic,
      PGPRs has the potential to promote saline soil-based agriculture. Halophytes are
      a useful reservoir of halotolerant bacteria with plant growth-promoting
      capabilities. Here, we review recent studies on the use of halophilic PGPRs to
      stimulate plant growth and increase the tolerance of non-halophytic crops to
      salinity. These studies illustrate that halophilic PGPRs from the rhizosphere of
      halophytic species can be effective bio-inoculants for promoting the production
      of non-halophytic species in saline soils. These studies support the viability of
      bioinoculation with halophilic PGPRs as a strategy for the sustainable
      enhancement of non-halophytic crop growth. The potential of this strategy is
      discussed within the context of ensuring sustainable food production for a world
      with an increasing population and continuing climate change. We also explore
      future research needs for using halotolerant PGPRs under salinity stress.

PMID- 29472911
TI  - A Novel Bifunctional Endolytic Alginate Lyase with Variable Alginate-Degrading
      Modes and Versatile Monosaccharide-Producing Properties.
AB  - Endo-type alginate lyases usually degrade alginate completely into various size
      defined unsaturated oligosaccharide products (>=disaccharides), while exoenzymes
      primarily produce monosaccharide products including saturated mannuronate (M) and
      guluronate (G) units and particularly unsaturated Delta units. Recently, two
      bifunctional alginate lyases have been identified as endolytic but M- and G
      producing with variable action modes. However, endolytic Delta-producing alginate
      lyases remain undiscovered. Herein, a new Flammeovirga protein, Aly2, was
      classified into the polysaccharide lyase 7 superfamily. The recombinant enzyme
      and its truncated protein showed similar stable biochemical characteristics.
      Using different sugar chains as testing substrates, we demonstrated that the two
      enzymes are bifunctional while G-preferring, endolytic whereas monosaccharide
      producing. Furthermore, the catalytic module of Aly2 can vary the action modes
      depending on the terminus type, molecular size, and M/G content of the substrate,
      thereby yielding different levels of M, G, and Delta units. Notably, the enzymes
      preferentially produce Delta units when digesting small size-defined
      oligosaccharide substrates, particularly the smallest substrate (unsaturated
      tetrasaccharide fractions). Deletion of the non-catalytic region of Aly2 caused
      weak changes in the action modes and biochemical characteristics. This study
      provided extended insights into alginate lyase groups with variable action modes
      for accurate enzyme use.

PMID- 29472910
TI  - Exploring the Genomic Traits of Non-toxigenic Vibrio parahaemolyticus Strains
      Isolated in Southern Chile.
AB  - Vibrio parahaemolyticus is the leading cause of seafood-borne gastroenteritis
      worldwide. As reported in other countries, after the rise and fall of the
      pandemic strain in Chile, other post-pandemic strains have been associated with
      clinical cases, including strains lacking the major toxins TDH and TRH. Since the
      presence or absence of tdh and trh genes has been used for diagnostic purposes
      and as a proxy of the virulence of V. parahaemolyticus isolates, the
      understanding of virulence in V. parahaemolyticus strains lacking toxins is
      essential to detect these strains present in water and marine products to avoid
      possible food-borne infection. In this study, we characterized the genome of four
      environmental and two clinical non-toxigenic strains (tdh-, trh-, and T3SS2-).
      Using whole-genome sequencing, phylogenetic, and comparative genome analysis, we
      identified the core and pan-genome of V. parahaemolyticus of strains of southern
      Chile. The phylogenetic tree based on the core genome showed low genetic
      diversity but the analysis of the pan-genome revealed that all strains harbored
      genomic islands carrying diverse virulence and fitness factors or prophage-like
      elements that encode toxins like Zot and RTX. Interestingly, the three strains
      carrying Zot-like toxin have a different sequence, although the alignment showed
      some conserved areas with the zot sequence found in V. cholerae. In addition, we
      identified an unexpected diversity in the genetic architecture of the T3SS1 gene
      cluster and the presence of the T3SS2 gene cluster in a non-pandemic
      environmental strain. Our study sheds light on the diversity of V.
      parahaemolyticus strains from the southern Pacific which increases our current
      knowledge regarding the global diversity of this organism.

PMID- 29472912
TI  - The Antimicrobial Activity of a Carbon Monoxide Releasing Molecule (EBOR-CORM-1)
      Is Shaped by Intraspecific Variation within Pseudomonas aeruginosa Populations.
AB  - Carbon monoxide releasing molecules (CORMs) have been suggested as a new
      synthetic class of antimicrobials to treat bacterial infections. Here we utilized
      a novel EBOR-CORM-1 ([NEt4][MnBr2(CO)4]) capable of water-triggered CO-release,
      and tested its efficacy against a collection of clinical Pseudomonas aeruginosa
      strains that differ in infection-related virulence traits. We found that while
      EBOR-CORM-1 was effective in clearing planktonic and biofilm cells of P.
      aeruginosa strain PAO1 in a concentration dependent manner, this effect was less
      clear and varied considerably between different P. aeruginosa cystic fibrosis
      (CF) lung isolates. While a reduction in cell growth was observed after 8 h of
      CORM application, either no effect or even a slight increase in cell densities
      and the amount of biofilm was observed after 24 h. This variation could be partly
      explained by differences in bacterial virulence traits: while CF isolates showed
      attenuated in vivo virulence and growth compared to strain PAO1, they formed much
      more biofilm, which could have potentially protected them from the CORM. Even
      though no clear therapeutic benefits against a subset of isolates was observed in
      an in vivo wax moth acute infection model, EBOR-CORM-1 was more efficient at
      reducing the growth of CF isolate co-culture populations harboring intraspecific
      variation, in comparison with efficacy against more uniform single isolate
      culture populations. Together these results suggest that CORMs could be effective
      at controlling genetically diverse P. aeruginosa populations typical for natural
      chronic CF infections and that the potential benefits of some antibiotics might
      not be observed if tested only against clonal bacterial populations.

PMID- 29472913
TI  - Benzyl-2-Acetamido-2-Deoxy-alpha-d-Galactopyranoside Increases Human
      Immunodeficiency Virus Replication and Viral Outgrowth Efficacy In Vitro.
AB  - Glycosylation of host and viral proteins is an important posttranslational
      modification needed to ensure correct function of glycoproteins. For this reason,
      we asked whether inhibition of O-glycosylation during human immunodeficiency
      virus (HIV) in vitro replication could affect HIV infectivity and replication
      rates. We used benzyl-2-acetamido-2-deoxy-alpha-d-galactopyranoside (BAGN), a
      compound that has been widely used to inhibit O-glycosylation in several cell
      lines. Pretreatment and culture of PHA-blast target cells with BAGN increased the
      percentage of HIV-infected cells (7.6-fold, p = 0.0115), the per-cell amount of
      HIV p24 protein (1.3-fold, p = 0.2475), and the viral particles in culture
      supernatants (7.1-fold, p = 0.0029) compared to BAGN-free cultures. Initiating
      infection with virus previously grown in the presence of BAGN further increased
      percentage of infected cells (30-fold, p < 0.0001), intracellular p24 (1.5-fold,
      p = 0.0433), and secreted viral particles (74-fold, p < 0.0001). BAGN-treated
      target cells showed less CD25 and CCR5 expression, but increased HLA-DR surface
      expression, which positively correlated with the number of infected cells.
      Importantly, BAGN improved viral outgrowth kinetics in 66% of the samples tested,
      including samples from HIV controllers and subjects in whom no virus could be
      expanded in the absence of BAGN. Sequencing of the isolated virus indicated no
      skewing of viral quasi-species populations when compared to BAGN-free culture
      conditions. BAGN also increased virus production in the ACH2 latency model when
      used together with latency-reversing agents. Taken together, our results identify
      BAGN treatment as a simple strategy to improve viral outgrowth in vitro and may
      provide novel insights into host restriction mechanisms and O-glycosylation
      related therapeutic targets for HIV control strategies.

PMID- 29472915
TI  - Endothelial Cell Focal Adhesion Regulates Transendothelial Migration and
      Subendothelial Crawling of T Cells.
AB  - Leukocytes circulating in the blood stream leave out of blood vessels and
      infiltrate into inflamed tissues to perform immune responses. Endothelial cells
      (ECs) lining interior of the post-capillary venules regulate various steps of
      leukocyte extravasation. In response to inflammatory signals, ECs upregulate
      adhesion molecules and produce/present chemokines to support firm adhesion and
      intraluminal crawling of leukocytes. They also remodel junctions to facilitate
      leukocyte transendothelial migration (TEM). While roles of apical/lateral
      components of EC layers in regulating leukocyte extravasation have been
      extensively investigated, relatively little attention has been paid to the basal
      part of EC layers comprising subendothelial spaces. In this study, we employed
      interference reflection microscopy (IRM), a microscopy technique specialized for
      label-free visualization of cell-substrate contact, to study detailed dynamic
      interactions between basal part of ECs and T cells underneath EC monolayer. For
      TEM, T cells on EC monolayer extended protrusions through junctions to explore
      subendothelial spaces, and EC focal adhesions (EC-FAs) acted as physical barrier
      for the protrusion. Therefore, preferential TEM occurred through junctions where
      near-junction focal adhesion (NJ-FA) density of ECs was low. After TEM, T cells
      performed subendothelial crawling (SEC) with flattened morphology and reduced
      migration velocity due to tight confinement. T cell SEC mostly occurred through
      gaps formed in between EC-FAs with minimally breaking EC-FAs. Tumor necrosis
      factor-alpha (TNF-alpha) treatment significantly loosened confinement in
      subendothelial spaces and reduced NJ-FA density of ECs, thus remodeled basal part
      of EC layer to facilitate leukocyte extravasation.

PMID- 29472914
TI  - Monocyte-Derived Signals Activate Human Natural Killer Cells in Response to
      Leishmania Parasites.
AB  - Activated natural killer (NK) cells release interferon (IFN)-gamma, which is
      crucial for the control of intracellular pathogens such as Leishmania. In
      contrast to experimental murine leishmaniasis, the human NK cell response to
      Leishmania is still poorly characterized. Here, we investigated the interaction
      of human blood NK cells with promastigotes of different Leishmania species
      (Leishmania major, Leishmania mexicana, Leishmania infantum, and Leishmania
      donovani). When peripheral blood mononuclear cells or purified NK cells and
      monocytes (all derived from healthy blood donors from Germany without a history
      of leishmaniasis) were exposed to promastigotes, NK cells showed increased
      surface expression of the activation marker CD69. The extent of this effect
      varied depending on the Leishmania species; differences between dermotropic and
      viscerotropic L. infantum strains were not observed. Upregulation of CD69
      required direct contact between monocytes and Leishmania and was partly
      inhibitable by anti-interleukin (IL)-18. Unexpectedly, IL-18 was undetectable in
      most of the supernatants (SNs) of monocyte/parasite cocultures. Confocal
      fluorescence microscopy of non-permeabilized cells revealed that Leishmania
      infected monocytes trans-presented IL-18 to NK cells. Native, but not heat
      treated SNs of monocyte/Leishmania cocultures also induced CD69 on NK cells,
      indicating the involvement of a soluble heat-labile factor other than IL-18. A
      role for the NK cell-activating cytokines IL-1beta, IL-2, IL-12, IL-15, IL-21,
      and IFN-alpha/beta was excluded. The increase of CD69 was not paralleled by NK
      cell IFN-gamma production or enhanced cytotoxicity. However, prior exposure of NK
      cells to Leishmania parasites synergistically increased their IFN-gamma release
      in response to IL-12, which was dependent on endogenous IL-18. CD1c+ dendritic
      cells were identified as possible source of Leishmania-induced IL-12. Finally, we
      observed that direct contact between Leishmania and NK cells reduced the
      expression of CD56 mRNA and protein on NK cells. We conclude that Leishmania
      activate NK cells via trans-presentation of IL-18 by monocytes and by a monocyte
      derived soluble factor. IL-12 is needed to elicit the IFN-gamma-response of NK
      cells, which is likely to be an important component of the innate control of the
      parasite.

PMID- 29472916
TI  - Fortunellin-Induced Modulation of Phosphatase and Tensin Homolog by MicroRNA-374a
      Decreases Inflammation and Maintains Intestinal Barrier Function in Colitis.
AB  - Activation of phosphatase and tensin homolog (PTEN) is known to induce cell
      apoptosis. MicroRNA-374a (miR-374a), which can suppress PTEN expression, has been
      found abnormally expressed in inflammatory bowel disease (IBD). Fortunellin is a
      citrus flavonoid that is a potential anti-inflammation agent in inflammatory
      diseases. The present study investigated the effects and mechanisms underlying
      fortunellin-induced inhibition of PTEN in IBD. Colitis was established in rats by
      the intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid to mimic
      human ulcerative colitis, which is the main type of IBD. miR-374a expression was
      measured by quantitative real-time polymerase chain reaction, and the regulation
      of PTEN by miR-374a was evaluated by dual luciferase reporter assay. Western
      blotting was used to measure the corresponding protein expression. Fortunellin
      ameliorated colitis symptoms, including excessive inflammation and oxidative
      stress. Fortunellin decreased epithelial cell apoptosis through inhibiting PTEN
      expression in colitis. Fortunellin-induced downregulation of PTEN could be
      counteracted by miR-374a depletion. Moreover, knockdown of miR-374a in vivo
      partly inhibited the effects of fortunellin on rat colitis. In conclusion, PTEN
      inhibition contributes to the amelioration effects of fortunellin on colitis. It
      was confirmed that fortunellin targets miR-374a, which is a negative regulator of
      PTEN. This study provides novel insights into the pathological mechanisms and
      treatment alternatives of colitis.

PMID- 29472917
TI  - Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis.
AB  - Objective: T-cells are critical players in the pathogenesis of osteoporosis in
      patients with rheumatoid arthritis (RA). Premature senescence of lymphocytes
      including the accumulation of senescent CD4+ T-cells is a hallmark feature of RA.
      Whether T-cell senescence is associated with bone loss in RA patients is elusive
      so far. Methods: This includes a prospective study of consecutive patients with
      RA (n = 107), patients with primary osteopenia/-porosis (n = 75), and healthy
      individuals (n = 38). Bone mineral density (BMD) was determined by dual-energy X
      ray absorptiometry scan. Flow cytometry, magnetic-associated cell sorting, and
      cell culture experiments were performed to analyze the pro-osteoclastic phenotype
      and the function of senescent CD4+CD28- T-cells. Results: Patients with
      osteopenia/-porosis yielded a higher prevalence of senescent CD4+CD28- T-cells
      than individuals with normal BMD, in the RA, as well as in the non-RA cohort.
      Receptor activator of nuclear factor kappa-B ligand (RANKL) was expressed at
      higher levels on CD4+CD28- T-cells as compared to CD28+ T-cells. Stimulation with
      interleukin-15 led to an up-regulation of RANKL expression, particularly on CD28-
      T-cells. CD4+CD28- T-cells induced osteoclastogenesis more efficiently than CD28+
      T-cells. Conclusion: Our data indicate that senescent T-cells promote
      osteoclastogenesis more efficiently than conventional CD28+ T-cells, which might
      contribute to the pathogenesis of systemic bone loss in RA and primary
      osteoporosis.

PMID- 29472918
TI  - Next-Generation Sequencing of Antibody Display Repertoires.
AB  - In vitro selection technology has transformed the development of therapeutic
      monoclonal antibodies. Using methods such as phage, ribosome, and yeast display,
      high affinity binders can be selected from diverse repertoires. Here, we review
      strategies for the next-generation sequencing (NGS) of phage- and other antibody
      display libraries, as well as NGS platforms and analysis tools. Moreover, we
      discuss recent examples relating to the use of NGS to assess library diversity,
      clonal enrichment, and affinity maturation.

PMID- 29472919
TI  - In the Absence of Central pre-B Cell Receptor Selection, Peripheral Selection
      Attempts to Optimize the Antibody Repertoire by Enriching for CDR-H3 Y101.
AB  - Sequential developmental checkpoints are used to "optimize" the B cell antigen
      receptor repertoire by minimizing production of autoreactive or useless
      immunoglobulins and enriching for potentially protective antibodies. The first
      and apparently most impactful checkpoint requires MUHC to form a functional pre-B
      cell receptor (preBCR) by associating with surrogate light chain, which is
      composed of VpreB and lambda5. Absence of any of the preBCR components causes a
      block in B cell development that is characterized by severe immature B cell
      lymphopenia. Previously, we showed that preBCR controls the amino acid content of
      the third complementary determining region of the H chain (CDR-H3) by using a
      VpreB amino acid motif (RDR) to select for tyrosine at CDR-H3 position 101
      (Y101). In antibodies bound to antigen, Y101 is commonly in direct contact with
      the antigen, thus preBCR selection impacts the antigen binding characteristics of
      the repertoire. In this work, we sought to determine the forces that shape the
      peripheral B cell repertoire when it is denied preBCR selection. Using
      bromodeoxyuridine incorporation and evaluation of apoptosis, we found that in the
      absence of preBCR there is increased turnover of B cells due to increased
      apoptosis. CDR-H3 sequencing revealed that this is accompanied by adjustments to
      DH identity, DH reading frame, JH, and CDR-H3 amino acid content. These
      adjustments in the periphery led to wild-type levels of CDR-H3 Y101 content among
      transitional (T1), mature recirculating, and marginal zone B cells. However,
      peripheral selection proved incomplete, with failure to restore Y101 levels in
      follicular B cells and increased production of dsDNA-binding IgM antibodies.

PMID- 29472921
TI  - Kinetics of HIV-Specific CTL Responses Plays a Minimal Role in Determining HIV
      Escape Dynamics.
AB  - Cytotoxic T lymphocytes (CTLs) have been suggested to play an important role in
      controlling human immunodeficiency virus (HIV-1 or simply HIV) infection. HIV,
      due to its high mutation rate, can evade recognition of T cell responses by
      generating escape variants that cannot be recognized by HIV-specific CTLs.
      Although HIV escape from CTL responses has been well documented, factors
      contributing to the timing and the rate of viral escape from T cells have not
      been fully elucidated. Fitness costs associated with escape and magnitude of the
      epitope-specific T cell response are generally considered to be the key in
      determining timing of HIV escape. Several previous analyses generally ignored the
      kinetics of T cell responses in predicting viral escape by either considering
      constant or maximal T cell response; several studies also considered escape from
      different T cell responses to be independent. Here, we focus our analysis on data
      from two patients from a recent study with relatively frequent measurements of
      both virus sequences and HIV-specific T cell response to determine impact of CTL
      kinetics on viral escape. In contrast with our expectation, we found that
      including temporal dynamics of epitope-specific T cell response did not improve
      the quality of fit of different models to escape data. We also found that for
      well-sampled escape data, the estimates of the model parameters including T cell
      killing efficacy did not strongly depend on the underlying model for escapes:
      models assuming independent, sequential, or concurrent escapes from multiple CTL
      responses gave similar estimates for CTL killing efficacy. Interestingly, the
      model assuming sequential escapes (i.e., escapes occurring along a defined
      pathway) was unable to accurately describe data on escapes occurring rapidly
      within a short-time window, suggesting that some of model assumptions must be
      violated for such escapes. Our results thus suggest that the current sparse
      measurements of temporal CTL dynamics in blood bear little quantitative
      information to improve predictions of HIV escape kinetics. More frequent
      measurements using more sensitive techniques and sampling in secondary lymphoid
      tissues may allow to better understand whether and how CTL kinetics impacts viral
      escape.

PMID- 29472922
TI  - Efficacy of T Regulatory Cells, Th17 Cells and the Associated Markers in
      Monitoring Tuberculosis Treatment Response.
AB  - Treatment monitoring is an essential aspect for tuberculosis (TB) disease
      management. Sputum smear microscopy is the only available tool for monitoring,
      but it suffers from demerits. Therefore, we sought to evaluate markers and
      cellular subsets of T regulatory (Treg) cells and T helper (Th) 17 cells in
      pulmonary TB patients (PTB) for TB treatment monitoring. Peripheral blood
      mononuclear cells (PBMCs) were stimulated in vitro (with purified protein
      derivative (PPD)) overnight which was followed by a polychromatic flow cytometry
      approach to study Treg and Th17 markers and cellular subsets in PTB (n = 12)
      undergoing antituberculous treatment (ATT). The baseline levels of these markers
      and cellular subsets were evaluated in normal healthy subjects (NHS). We observed
      a significant decrease in the expression of CD25 (p<0.01) marker and percentage
      of T-cell subsets like CD4+CD25+ (p<0.001) and CD4+CD25+CD39+ (p<0.05) at the end
      of intensive phase (IP) as well as in the continuation phase (CP) of ATT. A
      decrease in CD25 marker expression and percentage of CD4+CD25+ T cell subset
      showed a positive correlation to sputum conversion both in high and low sputum
      positive PTB. In eight PTB with cavitary lesions, only CD4+CD25+FoxP3 Treg subset
      manifested a significant decrease at the end of CP. Thus, results of this study
      show that CD25 marker and CD4+CD25+ T cells can serve as better markers for
      monitoring TB treatment efficacy. The Treg subset CD4+CD25+FoxP3 may be useful
      for prediction of favorable response in PTB with extensive lung lesions. However,
      these findings have to be evaluated in a larger patient cohort.

PMID- 29472920
TI  - Host Lipid Mediators in Leprosy: The Hypothesized Contributions to Pathogenesis.
AB  - The spectrum of clinical forms observed in leprosy and its pathogenesis are
      dictated by the host's immune response against Mycobacterium leprae, the
      etiological agent of leprosy. Previous results, based on metabolomics studies,
      demonstrated a strong relationship between clinical manifestations of leprosy and
      alterations in the metabolism of omega3 and omega6 polyunsaturated fatty acids
      (PUFAs), and the diverse set of lipid mediators derived from PUFAs. PUFA-derived
      lipid mediators provide multiple functions during acute inflammation, and some
      lipid mediators are able to induce both pro- and anti-inflammatory responses as
      determined by the cell surface receptors being expressed, as well as the cell
      type expressing the receptors. However, little is known about how these compounds
      influence cellular immune activities during chronic granulomatous infectious
      diseases, such as leprosy. Current evidence suggests that specialized pro
      resolving lipid mediators (SPMs) are involved in the down-modulation of the
      innate and adaptive immune response against M. leprae and that alteration in the
      homeostasis of pro-inflammatory lipid mediators versus SPMs is associated with
      dramatic shifts in the pathogenesis of leprosy. In this review, we discuss the
      possible consequences and present new hypotheses for the involvement of omega3
      and omega6 PUFA metabolism in the pathogenesis of leprosy. A specific emphasis is
      placed on developing models of lipid mediator interactions with the innate and
      adaptive immune responses and the influence of these interactions on the outcome
      of leprosy.

PMID- 29472923
TI  - A Prominent Role of Interleukin-18 in Acetaminophen-Induced Liver Injury
      Advocates Its Blockage for Therapy of Hepatic Necroinflammation.
AB  - Acetaminophen [paracetamol, N-acetyl-p-aminophenol (APAP)]-induced acute liver
      injury (ALI) not only remains a persistent clinical challenge but likewise stands
      out as well-characterized paradigmatic model of drug-induced liver damage. APAP
      intoxication associates with robust hepatic necroinflammation the role of which
      remains elusive with pathogenic but also pro-regenerative/-resolving functions
      being ascribed to leukocyte activation. Here, we shine a light on and put forward
      a unique role of the interleukin (IL)-1 family member IL-18 in experimental APAP
      induced ALI. Indeed, amelioration of disease as previously observed in IL-18
      deficient mice was further substantiated herein by application of the IL-18
      opponent IL-18-binding protein (IL-18BPd:Fc) to wild-type mice. Data altogether
      emphasize crucial pathological action of this cytokine in APAP toxicity. Adding
      recombinant IL-22 to IL-18BPd:Fc further enhanced protection from liver injury.
      In contrast to IL-18, the role of prototypic pro-inflammatory IL-1 and tumor
      necrosis factor-alpha is controversially discussed with lack of effects or even
      protective action being repeatedly reported. A prominent detrimental function for
      IL-18 in APAP-induced ALI as proposed herein should relate to its pivotal role
      for hepatic expression of interferon-gamma and Fas ligand, both of which
      aggravate APAP toxicity. As IL-18 serum levels increase in patients after APAP
      overdosing, targeting IL-18 may evolve as novel therapeutic option in those hard
      to-treat patients where standard therapy with N-acetylcysteine is unsuccessful.
      Being a paradigmatic experimental model of ALI, current knowledge on ill-fated
      properties of IL-18 in APAP intoxication likewise emphasizes the potential of
      this cytokine to serve as therapeutic target in other entities of inflammatory
      liver diseases.

PMID- 29472924
TI  - Signal Transducer and Activator of Transcription 3 Control of Human T and B Cell
      Responses.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a transcription
      factor that is activated downstream of many key cytokine receptors expressed by
      lymphocytes. As such, it plays a critical role in regulating B cells as well as
      CD4+ and CD8+ T cells. Patients with clinically significant immunodeficiency and
      immune dysregulation resulting from loss-of-function or gain-of-function
      mutations in STAT3 have been described. These individuals provide insight into
      the critical role of this transcription factor in the regulation of immune
      responses and the balance between effective immune protection and autoimmunity.

PMID- 29472926
TI  - Eliminating Factor H-Binding Activity of Borrelia burgdorferi CspZ Combined with
      Virus-Like Particle Conjugation Enhances Its Efficacy as a Lyme Disease Vaccine.
AB  - The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the
      most common tick-borne disease in the US and Europe. No potent human vaccine is
      currently available. The innate immune complement system is vital to host defense
      against pathogens, as complement activation on the surface of spirochetes results
      in bacterial killing. Complement system is inhibited by the complement regulator
      factor H (FH). To escape killing, B. burgdorferi produces an outer surface
      protein CspZ that binds FH to inhibit complement activation on the cell surface.
      Immunization with CspZ alone does not protect mice from infection, which we
      speculate is because FH-binding cloaks potentially protective epitopes. We
      modified CspZ by conjugating to virus-like particles (VLP-CspZ) and eliminating
      FH binding (modified VLP-CspZ) to increase immunogenicity. We observed greater
      bactericidal antibody titers in mice vaccinated with modified VLP-CspZ: A serum
      dilution of 1:395 (modified VLP-CspZ) vs 1:143 (VLP-CspZ) yielded 50%
      borreliacidal activity. Immunizing mice with modified VLP-CspZ cleared spirochete
      infection, as did passive transfer of elicited antibodies. This work developed a
      novel Lyme disease vaccine candidate by conjugating CspZ to VLP and eliminating
      FH-binding ability. Such a strategy of conjugating an antigen to a VLP and
      eliminating binding to the target ligand can serve as a general model for
      developing vaccines against other bacterial infectious agents.

PMID- 29472925
TI  - Understanding the Unfolded Protein Response in the Pathogenesis of Asthma.
AB  - Asthma is a heterogeneous, chronic inflammatory disease of the airways. It is a
      complex disease with different clinical phenotypes and results in a substantial
      socioeconomic burden globally. Poor understanding of pathogenic mechanisms of the
      disease hinders the investigation into novel therapeutics. Emerging evidence of
      the unfolded protein response (UPR) in the endoplasmic reticulum (ER) has
      demonstrated previously unknown functions of this response in asthma development.
      A worsening of asthmatic condition can be brought on by stimuli such as oxidative
      stress, pathogenic infections, and allergen exposure. All of which can induce ER
      stress and activate UPR leading to activation of different inflammatory responses
      and dysregulate the innate immune functions in the airways. The UPR as a central
      regulator of asthma pathogenesis may explain several unknown mechanism of the
      disease onset, which leads us in new directions for future asthma treatments. In
      this review, we summarize and discuss the causes and impact of ER-UPR in driving
      the pathogenesis of asthma and highlight its importance in clinical implications.

PMID- 29472927
TI  - Genome-Wide Identification of Destruxin A-Responsive Immunity-Related MicroRNAs
      in Diamondback Moth, Plutella xylostella.
AB  - Plutella xylostella, a global key pest, is one of the major lepidopteran pests of
      cruciferous vegetables owing to its strong ability of resistance development to a
      wide range of insecticides. Destruxin A, a mycotoxin of the entomopathogenic
      fungus, Metarhizium anisopliae, has broad-spectrum insecticidal effects and has
      been used as an alternative control strategy to reduce harmful effects of
      insecticides. However, microRNA (miRNA)-regulated reactions against destruxin A
      have not been elucidated yet. Therefore, here, to identify immunity-related
      miRNAs, we constructed four small RNA libraries from destruxin A-injected larvae
      of P. xylostella at three different time courses (2, 4, and 6 h) with a control,
      and sequenced by Illumina. Our results showed that totally 187 known and 44 novel
      miRNAs were identified in four libraries by bioinformatic analysis.
      Interestingly, among differentially expressed known miRNAs, some conserved
      miRNAs, such as miR-263, miR-279, miR-306, miR-2a, and miR-308, predicted to be
      involved in regulating immunity-related genes, were also identified. Worthy to
      mention, miR-306 and miR-279 were also listed as common abundantly expressed
      miRNA in all treatments. The Kyoto Encyclopedia of Genes and Genomes pathway
      analysis also indicated that differentially expressed miRNAs were involved in
      several immunity-related signaling pathways, including toll signaling pathway,
      IMD signaling pathway, JAK-STAT signaling pathway, and cell adhesion molecules
      signaling pathway. To the best of our knowledge, this is the first comprehensive
      report of destruxin A-responsive immunity-related miRNAs in P. xylostella. Our
      findings will improve in understanding the role of destruxin A-responsive miRNAs
      in the host immune system and would be useful to develop biological control
      strategies for controlling P. xylostella.

PMID- 29472929
TI  - Infectious Sporozoites of Plasmodium berghei Effectively Activate Liver CD8alpha+
      Dendritic Cells.
AB  - Immunization with radiation-attenuated sporozoites (RAS) shown to confer complete
      sterile protection against Plasmodia liver-stage (LS) infection that lasts about
      6 to 9 months in mice. We have found that the intermittent infectious sporozoite
      challenge to immune mice following RAS vaccination extends the longevity of
      sterile protection by maintaining CD8+ T cell memory responses to LS infection.
      It is reported that CD8alpha+ dendritic cells (DCs) are involved in the induction
      of LS-specific CD8+ T cells following RAS or genetically attenuated parasite
      (GAP) vaccination. In this study, we demonstrate that CD8alpha+ DCs respond
      differently to infectious sporozoite or RAS inoculation. The higher accumulation
      and activation of CD8alpha+ DCs was seen in the liver in response to infectious
      sporozoite 72 h postinoculation and found to be associated with higher expression
      of chemokines (CCL-20 and CCL-21) and type I interferon response via toll-like
      receptor signaling in liver. Moreover, the infectious sporozoites were found to
      induce qualitative changes in terms of the increased MHCII expression as well as
      costimulatory molecules including CD40 on the CD8alpha+ DCs compared to RAS
      inoculation. We have also found that infectious sporozoite challenge increased
      CD40L-expressing CD4+ T cells, which could help CD8+ T cells in the liver through
      "licensing" of the antigen-presenting cells. Our results suggest that infectious
      sporozoite challenge to prior RAS immunized mice modulates the CD8alpha+ DCs,
      which might be shaping the fate of memory CD8+ T cells against Plasmodium LS
      infection.

PMID- 29472928
TI  - Immunothrombotic Activity of Damage-Associated Molecular Patterns and
      Extracellular Vesicles in Secondary Organ Failure Induced by Trauma and Sterile
      Insults.
AB  - Despite significant improvements in injury prevention and emergency response,
      injury-related death and morbidity continues to increase in the US and worldwide.
      Patients with trauma, invasive operations, anti-cancer treatment, and organ
      transplantation produce a host of danger signals and high levels of pro
      inflammatory and pro-thrombotic mediators, such as damage-associated molecular
      patterns (DAMPs) and extracellular vesicles (EVs). DAMPs (e.g., nucleic acids,
      histone, high-mobility group box 1 protein, and S100) are molecules released from
      injured, stressed, or activated cells that act as endogenous ligands of innate
      immune receptors, whereas EVs (e.g., microparticle and exosome) are membranous
      vesicles budding off from plasma membranes and act as messengers between cells.
      DAMPs and EVs can stimulate multiple innate immune signaling pathways and
      coagulation cascades, and uncontrolled DAMP and EV production causes systemic
      inflammatory and thrombotic complications and secondary organ failure (SOF).
      Thus, DAMPs and EVs represent potential therapeutic targets and diagnostic
      biomarkers for SOF. High plasma levels of DAMPs and EVs have been positively
      correlated with mortality and morbidity of patients or animals with trauma or
      surgical insults. Blocking or neutralizing DAMPs using antibodies or small
      molecules has been demonstrated to ameliorate sepsis and SOF in animal models.
      Furthermore, a membrane immobilized with nucleic acid-binding polymers captured
      and removed multiple DAMPs and EVs from extracellular fluids, thereby preventing
      the onset of DAMP- and EV-induced inflammatory and thrombotic complications in
      vitro and in vivo. In this review, we will summarize the current state of
      knowledge of DAMPs, EVs, and SOF and discuss potential therapeutics and
      preventive intervention for organ failure secondary to trauma, surgery, anti
      cancer therapy, and allogeneic transplantation.

PMID- 29472930
TI  - Impaired Control of Epstein-Barr Virus Infection in B-Cell Expansion with NF
      kappaB and T-Cell Anergy Disease.
AB  - B-cell expansion with NF-kappaB and T-cell anergy (BENTA) disease is a B-cell
      specific lymphoproliferative disorder caused by germline gain-of-function
      mutations in CARD11. These mutations force the CARD11 scaffold into an open
      conformation capable of stimulating constitutive NF-kappaB activation in
      lymphocytes, without requiring antigen receptor engagement. Many BENTA patients
      also suffer from recurrent infections, with 7 out of 16 patients exhibiting
      chronic, low-grade Epstein-Barr virus (EBV) viremia. In this mini-review, we
      discuss EBV infection in the pathogenesis and clinical management of BENTA
      disease, and speculate on mechanisms that could explain inadequate control of
      viral infection in BENTA patients.

PMID- 29472931
TI  - Dendritic Cell Migration to Skin-Draining Lymph Nodes Is Controlled by Dermatan
      Sulfate and Determines Adaptive Immunity Magnitude.
AB  - For full activation of naive adaptive lymphocytes in skin-draining lymph nodes
      (LNs), presentation of peptide:MHC complexes by LN-resident and skin-derived
      dendritic cells (DCs) that encountered antigens (Ags) is an absolute
      prerequisite. To get to the nearest draining LN upon intradermal immunization,
      DCs need to migrate from the infection site to the afferent lymphatics, which can
      only be reached by traversing a collagen-dense network located in the dermis of
      the skin through the activity of proteolytic enzymes. Here, we show that mice
      with altered collagen fibrillogenesis resulting in thicker collagen fibers in the
      skin display a reduced DC migration to the draining LN upon immune challenge.
      Consequently, the initiation of the cellular and humoral immune response was
      diminished. Ag-specific CD8+ and CD4+ T cells as well as Ag-specific germinal
      center B cells and serum immunoglobulin levels were significantly decreased.
      Hence, we postulate that alterations to the production of extracellular matrix,
      as seen in various connective tissue disorders, may in the end affect the
      qualitative outcome of adaptive immunity.

PMID- 29472932
TI  - In Vitro-Generated Tc17 Cells Present a Memory Phenotype and Serve As a Reservoir
      of Tc1 Cells In Vivo.
AB  - Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they
      can mediate long-term protection against tumors. However, the therapeutic
      potential of different in vitro-generated CD8+ T cell effector subsets to persist
      and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1)
      cells produce interferon-gamma and are endowed with high cytotoxic capacity,
      whereas IL-17-producing CD8+ T (Tc17) cells are less cytotoxic but display
      enhanced self-renewal capacity. We sought to evaluate the functional properties
      of in vitro-generated Tc17 cells and elucidate their potential to become long
      lasting memory cells. Our results show that in vitro-generated Tc17 cells display
      a greater in vivo persistence and expansion in response to secondary antigen
      stimulation compared to Tc1 cells. When transferred into recipient mice, Tc17
      cells persist in secondary lymphoid organs, present a recirculation behavior
      consistent with central memory T cells, and can shift to a Tc1 phenotype.
      Accordingly, Tc17 cells are endowed with a higher mitochondrial spare respiratory
      capacity than Tc1 cells and express higher levels of memory-related molecules
      than Tc1 cells. Together, these results demonstrate that in vitro-generated Tc17
      cells acquire a central memory program and provide a lasting reservoir of Tc1
      cells in vivo, thus supporting the use of Tc17 lymphocytes in the design of novel
      and more effective therapies.

PMID- 29472933
TI  - Leucine-Rich Repeat Kinase 2 Controls the Ca2+/Nuclear Factor of Activated T
      Cells/IL-2 Pathway during Aspergillus Non-Canonical Autophagy in Dendritic Cells.
AB  - The Parkinson's disease-associated protein, Leucine-rich repeat kinase 2 (LRRK2),
      a known negative regulator of nuclear factor of activated T cells (NFAT), is
      expressed in myeloid cells such as macrophages and dendritic cells (DCs) and is
      involved in the host immune response against pathogens. Since, the Ca2+/NFAT/IL-2
      axis has been previously found to regulate DC response to the fungus Aspergillus,
      we have investigated the role played by the kinase LRRK2 during fungal infection.
      Mechanistically, we found that in the early stages of the non-canonical
      autophagic response of DCs to the germinated spores of Aspergillus, LRRK2
      undergoes progressive degradation and regulates NFAT translocation from the
      cytoplasm to the nucleus. Our results shed new light on the complexity of the
      Ca2+/NFAT/IL-2 pathway, where LRRK2 plays a role in controlling the immune
      response of DCs to Aspergillus.

PMID- 29472934
TI  - Alleviation of Nitrogen and Sulfur Deficiency and Enhancement of Photosynthesis
      in Arabidopsis thaliana by Overexpression of Uroporphyrinogen III
      Methyltransferase (UPM1).
AB  - Siroheme, an iron-containing tetrapyrrole, is the prosthetic group of nitrite
      reductase (NiR) and sulfite reductase (SiR); it is synthesized from
      uroporphyrinogen III, an intermediate of chlorophyll biosynthesis, and is
      required for nitrogen (N) and sulfur (S) assimilation. Further, uroporphyrinogen
      III methyltransferase (UPM1), responsible for two methylation reactions to form
      dihydrosirohydrochlorin, diverts uroporphyrinogen III from the chlorophyll
      biosynthesis pathway toward siroheme synthesis. AtUPM1 [At5g40850] was used to
      produce both sense and antisense plants of Arabidopsis thaliana in order to
      modulate siroheme biosynthesis. In our experiments, overexpression of AtUPM1
      signaled higher NiR (NII) and SiR gene and gene product expression. Increased NII
      expression was found to regulate and enhance the transcript and protein abundance
      of nitrate reductase (NR). We suggest that elevated NiR, NR, and SiR expression
      must have contributed to the increased synthesis of S containing amino acids in
      AtUPM1overexpressors, observed in our studies. We note that due to higher N and S
      assimilation in these plants, total protein content had increased in these
      plants. Consequently, chlorophyll biosynthesis increased in these sense plants.
      Higher chlorophyll and protein content of plants upregulated photosynthetic
      electron transport and carbon assimilation in the sense plants. Further, we have
      observed increased plant biomass in these plants, and this must have been due to
      increased N, S, and C assimilation. On the other hand, in the antisense plants,
      the transcript abundance, and protein content of NiR, and SiR was shown to
      decrease, resulting in reduced total protein and chlorophyll content. This led to
      a decrease in photosynthetic electron transport rate, carbon assimilation and
      plant biomass in these antisense plants. Under nitrogen or sulfur starvation
      conditions, the overexpressors had higher protein content and photosynthetic
      electron transport rate than the wild type (WT). Conversely, the antisense plants
      had lower protein content and photosynthetic efficiency in N-deficient
      environment. Our results clearly demonstrate that upregulation of siroheme
      biosynthesis leads to increased nitrogen and sulfur assimilation, and this
      imparts tolerance to nitrogen and sulfur deficiency in Arabidopsis thaliana
      plants.

PMID- 29472936
TI  - Durum Wheat Landraces from East and West Regions of the Mediterranean Basin Are
      Genetically Distinct for Yield Components and Phenology.
AB  - Genetic diversity of durum wheat landraces is a powerful tool for the
      introgression of new alleles of commercial interest in breeding programs. In a
      previous study, our team structured a collection of 172 durum wheat landraces
      from 21 Mediterranean countries in four genetic populations related to their
      geographical origin: east Mediterranean (17), east Balkan and Turkey (23), west
      Balkan and Egypt (25), and West Mediterranean (73), leaving 34 genotypes as
      admixed, and association mapping was carried out for important agronomic traits.
      Using a subset of this collection, the current study identified 23 marker alleles
      with a differential frequency in landraces from east and west regions of the
      Mediterranean Basin, which affected important agronomic traits. Eastern landraces
      had higher frequencies than the western ones of alleles increasing the number of
      spikes (wPt-5385 on chromosome 1B), grains per m2 (wPt-0841 on chromosome 7B),
      and grain filling duration (7 significant marker trait associations). Eastern
      landraces had higher frequencies of marker alleles located on chromosomes 4A, 5B,
      and 6B associated with reduced cycle length, and lighter grains than the western
      ones. Also for lower kernel weight, four marker alleles were located on
      chromosome 1A. Breeders may use the molecular markers identified in the current
      study for improving yield under specific Mediterranean environments.

PMID- 29472935
TI  - Chlorophyll Fluorescence Video Imaging: A Versatile Tool for Identifying Factors
      Related to Photosynthesis.
AB  - Measurements of chlorophyll fluorescence provide an elegant and non-invasive
      means of probing the dynamics of photosynthesis. Advances in video imaging of
      chlorophyll fluorescence have now made it possible to study photosynthesis at all
      levels from individual cells to entire crop populations. Since the technology
      delivers quantitative data, is easily scaled up and can be readily combined with
      other approaches, it has become a powerful phenotyping tool for the
      identification of factors relevant to photosynthesis. Here, we review genetic
      chlorophyll fluorescence-based screens of libraries of Arabidopsis and
      Chlamydomonas mutants, discuss its application to high-throughput phenotyping in
      quantitative genetics and highlight potential future developments.

PMID- 29472937
TI  - Quantitative Trait Transcripts Mapping Coupled with Expression Quantitative Trait
      Loci Mapping Reveal the Molecular Network Regulating the Apetalous Characteristic
      in Brassica napus L.
AB  - The apetalous trait of rapeseed (Brassica napus, AACC, 2n = 38) is important for
      breeding an ideal high-yield rapeseed with superior klendusity to Sclerotinia
      sclerotiorum. Currently, the molecular mechanism underlying the apetalous trait
      of rapeseed is unclear. In this study, 14 petal regulators genes were chosen as
      target genes (TGs), and the expression patterns of the 14 TGs in the AH
      population, containing 189 recombinant inbred lines derived from a cross between
      apetalous "APL01" and normal "Holly," were analyzed in two environments using qRT
      PCR. Phenotypic data of petalous degree (PDgr) in the AH population were obtained
      from the two environments. Both quantitative trait transcript (QTT)-association
      mapping and expression QTL (eQTL) analyses of TGs expression levels were
      performed to reveal regulatory relationships among TGs and PDgr. QTT mapping for
      PDgr determined that PLURIPETALA (PLP) was the major negative QTT associated with
      PDgr in both environments, suggesting that PLP negatively regulates the petal
      development of line "APL01." The QTT mapping of PLP expression levels showed that
      CHROMATIN-REMODELING PROTEIN 11 (CHR11) was positively associated with PLP
      expression, indicating that CHR11 acts as a positive regulator of PLP expression.
      Similarly, QTT mapping for the remaining TGs identified 38 QTTs, associated with
      13 TGs, and 31 QTTs, associated with 10 TGs, respectively, in the first and
      second environments. Additionally, eQTL analyses of TG expression levels showed
      that 12 and 11 unconditional eQTLs were detected in the first and second
      environment, respectively. Based on the QTTs and unconditional eQTLs detected, we
      presented a hypothetical molecular regulatory network in which 14 petal
      regulators potentially regulated the apetalous trait in "APL01" through the CHR11
      PLP pathway. PLP acts directly as the terminal signal integrator negatively
      regulating petal development in the CHR11-PLP pathway. These findings will aid in
      the understanding the molecular mechanism underlying the apetalous trait of
      rapeseed.

PMID- 29472938
TI  - Novel alpha-Tubulin Mutations Conferring Resistance to Dinitroaniline Herbicides
      in Lolium rigidum.
AB  - The dinitroaniline herbicides (particularly trifluralin) have been globally used
      in many crops for selective grass weed control. Consequently, trifluralin
      resistance has been documented in several important crop weed species and has
      recently reached a level of concern in Australian Lolium rigidum populations.
      Here, we report novel mutations in the L. rigidum alpha-tubulin gene which confer
      resistance to trifluralin and other dinitroaniline herbicides. Nucleotide
      mutations at the highly conserved codon Arg-243 resulted in amino acid
      substitutions of Met or Lys. Rice calli transformed with the mutant 243-Met or
      243-Lys alpha-tubulin genes were 4- to 8-fold more resistant to trifluralin and
      other dinitroaniline herbicides (e.g., ethalfluralin and pendimethalin) compared
      to calli transformed with the wild type alpha-tubulin gene from L. rigidum.
      Comprehensive modeling of molecular docking predicts that Arg-243 is close to the
      trifluralin binding site on the alpha-tubulin surface and that replacement of Arg
      243 by Met/Lys-243 results in a spatial shift of the trifluralin binding domain,
      reduction of trifluralin-tubulin contacts, and unfavorable interactions. The
      major effect of these substitutions is a significant rise of free interaction
      energy between alpha-tubulin and trifluralin, as well as between trifluralin and
      its whole molecular environment. These results demonstrate that the Arg-243
      residue in alpha-tubulin is a determinant for trifluralin sensitivity, and the
      novel Arg-243-Met/Lys mutations may confer trifluralin resistance in L. rigidum.

PMID- 29472939
TI  - Dominant Species in Subtropical Forests Could Decrease Photosynthetic N
      Allocation to Carboxylation and Bioenergetics and Enhance Leaf Construction Costs
      during Forest Succession.
AB  - It is important to understand how eco-physiological characteristics shift in
      forests when elucidating the mechanisms underlying species replacement and the
      process of succession and stabilization. In this study, the dominant species at
      three typical successional stages (early-, mid-, and late-succession) in the
      subtropical forests of China were selected. At each stage, we compared the leaf
      construction costs (CC), payback time (PBT), leaf area based N content (NA),
      maximum CO2 assimilation rate (Pmax), specific leaf area (SLA), photosynthetic
      nitrogen use efficiency (PNUE), and leaf N allocated to carboxylation (NC), and
      to bioenergetics (NB). The relationships between these leaf functional traits
      were also determined. The results showed that the early-succession forest is
      characterized with significantly lower leaf CC, PBT, NA, but higher Pmax, SLA,
      PNUE, NC, and NB, in relation to the late-succession forest. From the early- to
      the late-succession forests, the relationship between Pmax and leaf CC
      strengthened, whereas the relationships between NB, NC, PNUE, and leaf CC
      weakened. Thus, the dominant species are able to decrease the allocation of the
      photosynthetic N fraction to carboxylation and bioenergetics during forest
      succession. The shift in these leaf functional traits and their linkages might
      represent a fundamental physiological mechanism that occurs during forest
      succession and stabilization.

PMID- 29472940
TI  - Inheritance and Linkage of Virulence Genes in Chinese Predominant Race CYR32 of
      the Wheat Stripe Rust Pathogen Puccinia striiformis f. sp. tritici.
AB  - Puccinia striiformis f.sp. tritici (Pst) is the causal agent of stripe (yellow)
      rust on wheat. It seriously threatens wheat production worldwide. The obligate
      biotrophic fungus is highly capable of producing new virulent races that can
      overcome resistance. Studying the inheritance of Pst virulence using the
      classical genetic approach was not possible until the recent discovery of its
      sexual stage on barberry plants. In the present study, 127 progeny isolates were
      obtained by selfing a representative Chinese Yellow Rust (CYR) race, CYR32, on
      Berberis aggregate. The parental isolate and progeny isolates were characterized
      by testing them on 25 wheat lines with different Yr genes for resistance and 10
      simple sequence repeat (SSR) markers. The 127 progeny isolates were classified
      into 27 virulence phenotypes (VPs), and 65 multi-locus genotypes (MLGs). All
      progeny isolates and the parental isolate were avirulent to Yr5, Yr8, Yr10, Yr15,
      Yr24, Yr26, Yr32, and YrTr1; but virulent to Yr1, Yr2, Yr3, Yr4, Yr25, Yr44, and
      Yr76. The VPs of the parental isolate to nine Yr genes (Yr6, Yr7, Yr9, Yr17,
      Yr27, Yr28, Yr43, YrA, and YrExp2) and the avirulence phenotype to YrSP were
      found to be heterozygous. Based on the segregation of the virulence/avirulence
      phenotypes, we found that the VPs to Yr7, Yr28, Yr43, and YrExp2 were controlled
      by a dominant gene; those to Yr6, Yr9, and YrA (Yr73, Yr74) by two dominant
      genes; those to Yr17 and Yr27 by one dominant and one recessive gene; and the
      avirulence phenotype to YrSP by two complementary dominant genes. Molecular
      mapping revealed the linkage of 10 virulence/avirulence genes. Comparison of the
      inheritance modes of the virulence/avirulence genes in this study with previous
      studies indicated complex interactions between virulence genes in the pathogen
      and resistance genes in wheat lines. The results are useful for understanding the
      plant-pathogen interactions and developing wheat cultivars with effective and
      durable resistance.

PMID- 29472942
TI  - Function of Plant DExD/H-Box RNA Helicases Associated with Ribosomal RNA
      Biogenesis.
AB  - Ribosome biogenesis is a highly complex process that requires several cofactors,
      including DExD/H-box RNA helicases (RHs). RHs are a family of ATPases that
      rearrange the secondary structures of RNA and thus remodel ribonucleoprotein
      complexes. DExD/H-box RHs are found in most organisms and play critical roles in
      a variety of RNA-involved cellular events. In human and yeast cells, many DExD/H
      box RHs participate in multiple steps of ribosome biogenesis and regulate
      cellular proliferation and stress responses. In plants, several DExD/H-box RHs
      have been demonstrated to be associated with plant development and abiotic stress
      tolerance through their functions in modulating pre-rRNA processing. In this
      review, we summarize the pleiotropic roles of DExD/H-box RHs in rRNA biogenesis
      and other biological functions. We also describe the overall function of the
      DExD/H-box RH family in ribosome biogenesis based on data from human and yeast.

PMID- 29472941
TI  - Plant Abiotic Stress Proteomics: The Major Factors Determining Alterations in
      Cellular Proteome.
AB  - HIGHLIGHTS: Major environmental and genetic factors determining stress-related
      protein abundance are discussed.Major aspects of protein biological function
      including protein isoforms and PTMs, cellular localization and protein
      interactions are discussed.Functional diversity of protein isoforms and PTMs is
      discussed. Abiotic stresses reveal profound impacts on plant proteomes including
      alterations in protein relative abundance, cellular localization, post
      transcriptional and post-translational modifications (PTMs), protein interactions
      with other protein partners, and, finally, protein biological functions. The main
      aim of the present review is to discuss the major factors determining stress
      related protein accumulation and their final biological functions. A dynamics of
      stress response including stress acclimation to altered ambient conditions and
      recovery after the stress treatment is discussed. The results of proteomic
      studies aimed at a comparison of stress response in plant genotypes differing in
      stress adaptability reveal constitutively enhanced levels of several stress
      related proteins (protective proteins, chaperones, ROS scavenging- and
      detoxification-related enzymes) in the tolerant genotypes with respect to the
      susceptible ones. Tolerant genotypes can efficiently adjust energy metabolism to
      enhanced needs during stress acclimation. Stress tolerance vs. stress
      susceptibility are relative terms which can reflect different stress-coping
      strategies depending on the given stress treatment. The role of differential
      protein isoforms and PTMs with respect to their biological functions in different
      physiological constraints (cellular compartments and interacting partners) is
      discussed. The importance of protein functional studies following high-throughput
      proteome analyses is presented in a broader context of plant biology. In summary,
      the manuscript tries to provide an overview of the major factors which have to be
      considered when interpreting data from proteomic studies on stress-treated
      plants.

PMID- 29472943
TI  - Do Galactolipid Synthases Play a Key Role in the Biogenesis of Chloroplast
      Membranes of Higher Plants?
AB  - A unique feature of chloroplasts is their high content of the galactolipids
      monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), which
      constitute up to 80% of their lipids. These galactolipids are synthesized in the
      chloroplast envelope membrane through the concerted action of
      galactosyltransferases, the so-called 'MGDG synthases (MGDs)' and 'DGDG synthases
      (DGDs),' which use uridine diphosphate (UDP)-galactose as donor. In Arabidopsis
      leaves, under standard conditions, the enzymes MGD1 and DGD1 provide the bulk of
      galactolipids, necessary for the massive expansion of thylakoid membranes. Under
      phosphate limited conditions, plants activate another pathway involving MGD2/MGD3
      and DGD2 to provide additional DGDG that is exported to extraplastidial membranes
      where they partly replace phospholipids, a phosphate-saving mechanism in plants.
      A third enzyme system, which relies on the UDP-Gal-independent GGGT (also called
      SFR2 for SENSITIVE TO FREEZING 2), can be activated in response to a freezing
      stress. The biosynthesis of galactolipids by these multiple enzyme sets must be
      tightly regulated to meet the cellular demand in response to changing
      environmental conditions. The cooperation between MGD and DGD enzymes with a
      possible substrate channeling from diacylglycerol to MGDG and DGDG is supported
      by biochemical and biophysical studies and mutant analyses reviewed herein. The
      fine-tuning of MGDG to DGDG ratio, which allows the reversible transition from
      the hexagonal II to lamellar alpha phase of the lipid bilayer, could be a key
      factor in thylakoid biogenesis.

PMID- 29472944
TI  - Roles of E3 Ubiquitin-Ligases in Nuclear Protein Homeostasis during Plant Stress
      Responses.
AB  - Ubiquitination, the reversible protein conjugation with ubiquitin (Ub), is a post
      translational modification that enables rapid and specific cellular responses to
      stimuli without requirement of de novo protein synthesis. Although ubiquitination
      also displays non-proteolytic functions, it often acts as a signal for selective
      protein degradation through the ubiquitin-proteasome system (UPS). In plants, it
      has become increasingly apparent that the UPS is a central regulator of many key
      cellular and physiological processes, including responses to biotic and abiotic
      stresses. In the nucleus, protein regulation via the UPS orchestrates gene
      expression, genome maintenance, and signal transduction. Here, we focus on E3 Ub
      ligase proteins as major components of the ubiquitination cascade that confer
      specificity of substrate recognition. We provide an overview on how they
      contribute to nuclear proteome plasticity during plant responses to environmental
      stress signals.

PMID- 29472945
TI  - An Update on Phosphodiesterase Mutations Underlying Genetic Etiology of Hearing
      Loss and Retinitis Pigmentosa.

PMID- 29472947
TI  - Comparison of the Prevalence of Psychiatric Disorders in Performance-Enhancing
      Drug Users and Nonuser Bodybuilders.
AB  - Objective: The present study aimed at comparing the prevalence of major
      psychiatric disorders including major depressive disorder, bipolar disorder,
      schizophrenia, and generalized anxiety disorder between performance-enhancing
      drug users and nonuser bodybuilders. Moreover, the prevalence of major
      psychiatric disorders in bodybuilders was also reported. Method: In this study,
      453 athletes were recruited from Bushehr bodybuilding gyms from February to May
      2015. A structured questionnaire was used to collect the participants'
      information, including demographic characteristics, sports' status and
      performance-enhancing drug use. According to the condition of performance
      enhancing drug use, the participants were divided into current users, non-current
      users, and nonusers. The psychiatric status of the participants was evaluated
      using DSM-IV diagnostic criteria for major depressive disorder, bipolar disorder,
      generalized anxiety disorder, and schizophrenia. We also asked about the acute
      psychotic disturbances after using performance-enhancing drugs, alcohol use, and
      history of aggressive behavior in bodybuilders. Data were analyzed using one-way
      analysis of variance and chi-square tests. Results: Prevalence of major
      depressive disorder, bipolar disorder, schizophrenia, generalized anxiety
      disorder, and the overall prevalence of psychiatric disorders in the bodybuilders
      was 19.7%, 3.8%, 1.5%, 16.6%, and 26.7%, respectively. After using performance
      enhancing drugs, 33% of the bodybuilders had experienced acute psychological
      disturbances. There were no significant differences between current, non-current,
      and nonuser bodybuilding athletes in the measured psychiatric disorders.
      Conclusion: Prevalence of psychiatric disorders was not significantly different
      in performance-enhancing drug users and nonusers. Thus, it can be concluded that
      performance-enhancing drugs do not increase the risk of psychiatric disorders in
      bodybuilders.

PMID- 29472946
TI  - Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse
      Sperm and Epididymosomes.
AB  - While the risks of maternal alcohol abuse during pregnancy are well-established,
      several preclinical studies suggest that chronic preconception alcohol
      consumption by either parent may also have significance consequences for
      offspring health and development. Notably, since isogenic male mice used in these
      studies are not involved in gestation or rearing of offspring, the cross
      generational effects of paternal alcohol exposure suggest a germline-based
      epigenetic mechanism. Many recent studies have demonstrated that the effects of
      paternal environmental exposures such as stress or malnutrition can be
      transmitted to the next generation via alterations to small noncoding RNAs in
      sperm. Therefore, we used high throughput sequencing to examine the effect of
      preconception ethanol on small noncoding RNAs in sperm. We found that chronic
      intermittent ethanol exposure altered several small noncoding RNAs from three of
      the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial
      small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were
      evaluated with RT-qPCR on a separate cohort of mice and five of the six were
      confirmed to be altered by chronic ethanol exposure, supporting the validity of
      the sequencing results. In addition to altered sperm RNA abundance, chronic
      ethanol exposure affected post-transcriptional modifications to sperm small
      noncoding RNAs, increasing two nucleoside modifications previously identified in
      mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal
      expression of a tRNA methyltransferase, Nsun2, known to directly regulate tDR
      biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in
      extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the
      hypothesis that alterations to sperm tDR emerge in the epididymis and that
      epididymosomes are the primary source of small noncoding RNAs in sperm. These
      results add chronic ethanol to the growing list of paternal exposures that can
      affect small noncoding RNA abundance and nucleoside modifications in sperm. As
      small noncoding RNAs in sperm have been shown to causally induce heritable
      phenotypes in offspring, additional research is warranted to understand the
      potential effects of ethanol-responsive sperm small noncoding RNAs on offspring
      health and development.

PMID- 29472948
TI  - Craving and Drug Reward: A Comparison of Celecoxib and Ibuprofen in Detoxifying
      Opiate Addicts.
AB  - Objective: Craving for substance abuse is a usual and complicated problem in
      patients, with opioid addiction who are in opioid detoxifying process. Craving
      has been added as one of the diagnostic criteria of substance use disorders in
      DSM-5. The present trial aimed at comparing the effects of celecoxib versus
      ibuprofen in reducing pain and decreasing the desire to use opiates in patients
      undergoing opiate detoxification (n = 32). Method: A total of 32 patients (both
      inpatients and outpatients), who were undergoing opiate detoxification procedure
      and met the inclusion criteria entered this 4- week study. Participants who
      suffered from pain due to opiate withdrawal were randomized into 2 groups: Group
      1 received celecoxib 200 milligrams once per day and group 2 received ibuprofen
      400 milligrams 4 times per day. Self-reported Desire for Drug Questionnaire (DDQ)
      and 0-10 numeric pain scale were used at baseline and at the end of the study to
      evaluate changes in opiate craving and pain, respectively. Data analysis was done
      by SPSS-21 statistical software. Results: In this study, 16 patients received
      celecoxib 200 milligrams once daily, and 16 received ibuprofen 400 milligrams 4
      times daily. After 4 weeks of treatment with both ibuprofen and celecoxib, the
      results revealed that celecoxib and ibuprofen equally reduced the pain symptoms.
      After 4 weeks of treatment, with either ibuprofen or celecoxib, significant
      improvement was observed in decreasing the craving in the celecoxib group, but
      not in the ibuprofen group. Conclusion: The study revealed a significant
      difference between the celecoxib and ibuprofen group in reducing craving in
      patients with opiate craving after 4 weeks of treatment. However there were no
      significant differences between these two groups in reducing pain.

PMID- 29472949
TI  - The Relationship between Motor, Imitation, and Early Social Communication Skills
      in Children with Autism.
AB  - Objective: Development of early social skills in children is a complex process.
      To understand this process, it is important to assess how strengths or weaknesses
      in other developmental domains may be affected by these skills. The present study
      aimed at investigating the association of motor skills and imitation ability with
      early social communication skills in children with autism spectrum disorder
      (ASD). Method: In this study, 20 children with ASD aged 3 to 5 years (M = 4.05,
      SD = 0.55) participated. All children were diagnosed as ASD based on the DSM-V
      criteria by an independent child psychiatrist. Additionally, Autism Diagnostic
      interview-Revised was used for subsequent diagnostic confirmation. Children were
      tested with Test of Gross Motor Development (TGMD-2), the Motor Imitation Scale
      (MIS), and the Early Social Communication Scales (ESCS). All examinations were
      videotaped for subsequent scoring. The relationship between these skills was
      estimated by Pearson correlation coefficient. Results: A significant and strong
      correlation was obtained between TGMD total score and imitation total score (r
      =.776; p <0.001). However, the relationship between MIS subscales and TGMD-2
      locomotor subtest scores was not significant (P>0.05). A significant correlation
      was found between MIS and TGMD total scores with Initiating Joint Attention and
      Responding to Joint Attention (p<=0/025) as ESCS subscales. But MIS and TGMD
      total scores were not correlated with social interaction and responding to
      behavioral requests subscales. Conclusion: The results of the present study
      showed that indicated both imitation ability and motor function have an
      association with each other and with early social communication skills.

PMID- 29472950
TI  - Psycho-Socio-Cultural Determinants of Food Choice: A Qualitative Study on Adults
      in Social and Cultural Context of Iran.
AB  - Objective: Food choice is a process through which people think, feel, and eat
      food. It does not only influence individuals' health and well-being, families and
      communities, but also it has an effect on regional, national, and global levels.
      This qualitative study was conducted to explore perceptions and lived experiences
      of Tehran adult residents on psychological, social and cultural determinants of
      food choice. Method: In this qualitative design, we recruited 33 adults aged 30
      to 64 years from various districts of Tehran, capital of Iran, and we explored
      how people make decisions about food choice in practice and shape their
      perception, attitude, and eating practices. An individual in-depth semi
      structured interview guide included major questions with follow-up probes was
      used to explore participants' current and past eating habits from childhood to
      adulthood, dietary change at different life courses, and effective psychological
      state on food selection in different seasons. Results: This study revealed that
      food choice in the studied adults (30-64 years old) was widely influenced by
      psychological, social, and cultural determinants, which can be categorized into 5
      main themes: cultural context and patterns; social Structure and norms;
      information resources and media; household and family structure; and nutrition
      transition. Conclusion: The findings clarified the importance of social and
      cultural contexts, which influence the food choice of adults in a metropolis like
      Tehran. Many of these concepts are contextualized from childhood. These findings
      could serve as guideline to design socio-culturally appropriate strategies and
      improve dietary behaviors of Iranians.

PMID- 29472951
TI  - Psychiatric Disorders and Personality Profiles of Middle-Aged Suicide Attempters
      with No Evidence of Specific Psychopathological Profiles Referred to an Emergency
      Department.
AB  - Objective: The present study aimed at assessing the sociodemographic and
      psychiatric characteristics of 40 to 65 year- old suicide attempters, who were
      referred to an emergency department within 4 hours of the attempt. Method: A
      total of 93 suicide attempters (Mean age=46.59 years) who were referred to an
      emergency department, were assessed in this study. Patients completed
      questionnaires covering sociodemographic data, personality traits, mood, and
      impulsivity. Psychiatric status of the patients was rated by experts. Results:
      Experts rated 85 (92.4%) of the suicide attempters as having a psychiatric
      disorder. Based on self-ratings and compared to normative data, 42 (46.6%)
      patients were psychopathologically ill. It was found that suicide attempts were
      not related to impulsive personality traits, mood disorders, sociodemographic
      patterns, or gender (gender-ratio: 1:1.58; f: m). Conclusion: The pattern of
      results suggests that further unknown factors were involved in pushing people to
      attempt suicide.

PMID- 29472952
TI  - Spiritual Psychotherapy for Adolescents with Conduct Disorder: Designing and
      Piloting a Therapeutic Package.
AB  - Objective: Spiritual psychotherapy has been conceptualized in the context of love
      and belief as principles of existence. Spiritual psychotherapy can provide an
      opportunity to design programs to treat conduct disorder. The aim of this study
      was to introduce the Spiritual Psychotherapy Package for Adolescents with Conduct
      Disorder and execute it as a pilot study. Method: The intervention is a manual
      guided program conducted over 14 group sessions, using the perspectives of object
      relations and attachment approach. It was executed for a group of eight
      adolescent boys with conduct disorder (mean age: 17.01 years) at Tehran
      reformatory. The Aggression Questionnaire and the Attachment to God Inventory
      were completed pre- and post-intervention. Results: There were no significant
      differences in outcome measures from pre- to post- intervention. Cohen's dav was
      applied to estimate the measure of the effect size in this study. Cohen's dav
      measures of avoidance and anxious attachment to God showed acceptable effect
      sizes. However, Cohen's dav measure of verbal aggression indicated a small effect
      size. Conclusion: We found evidence indicating acceptability of spiritual
      psychotherapy among adolescents with conduct disorder in attachment to God.

PMID- 29472953
TI  - Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived
      Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case
      Control Study.
AB  - Objective: Several studies have shown that some polymorphisms of genes encoding
      catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and
      norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve
      growth factor, are strong candidates for risk of schizophrenia (SCZ). In the
      present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF
      Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population.
      Method: This case- control study included 92 SCZ patients and 92 healthy controls
      (HCs). Genotyping of both variants (COMT Val158Met (G>A) and BDNF Val66Met (G>A))
      were conducted using Amplification Refractory Mutation System-Polymerase Chain
      Reaction (ARMS-PCR). Results: The findings revealed that the COMT Val158Met (G>A)
      polymorphism was not associated with the risk/protective of SCZ in all models
      (OR=0.630, 95%CI=0.299-1.326, P=0.224, GA vs. GG, OR=1.416, 95%CI=0.719-2.793,
      P=0.314, AA vs. GG, OR=1.00, 95%CI=0.56-1.79, P=1.00 GA+AA vs. GG, OR=1.667,
      95%CI=0.885-3.125, P=0.11, AA vs. GG+GA, OR=1.247, 95%CI=0.825-1.885, P=0.343, A
      vs. G,). However, BDNF Val66Met (G>A) variant increased the risk of SCZ (OR =
      2.008 95%CI = 1.008-4.00, P = 0.047, GA vs. GG, OR = 3.876 95%CI = 1.001-14.925,
      P = 0.049. AA vs. GG, OR = 2.272. 95%CI = 1.204-4.347, P = 0.011, GA+AA vs. GG,
      OR = 2.22 95%CI = 1.29-3.82. P = 0.005, A vs. G). Conclusion: The results did not
      support an association between COMT Val158Met (G>A) variant and risk/protective
      of SCZ. Moreover, it was found that BDNF Val66Met (G>A) polymorphism may increase
      the risk of SCZ development. Further studies and different ethnicities are
      recommended to confirm the findings.

PMID- 29472954
TI  - Evaluation of the Effectiveness of the Friends for Life Program on Children's
      Anxiety and Depression.
AB  - Objective: Anxiety disorders and depression during childhood and adolescence are
      among highly prevalent serious mental health problems, which lead to reduced
      performance in children and can also negatively affect children's emotional and
      social long-term development. This study, which was conducted in Mashhad in 2015,
      aimed at evaluating the effectiveness of the Friends for Life cognitive
      behavioral program in reducing the symptoms of anxiety and depression in
      children. Method: In this controlled clinical trial, 248 male students aged 10
      were screened for mild to moderate symptoms of anxiety and depression using the
      Revised Children's Manifest Anxiety (RCMA) and the Children's Depression
      Inventory (CDI). Of the participants, 40 students met the inclusion criteria. The
      demographic questionnaire, the Strengths and Difficulties Questionnaire (SDQ),
      and the Depression-Anxiety-Stress Scale (DASS) were filled out by parents. The
      children in the experimental group received the Friends for Life cognitive
      behavioral training program for eight 1-hour weekly sessions. RCMA, CDI, SDQ, and
      DASS were filled out again by both groups at the end of the sessions and 3 months
      later. To evaluate comparability between the 2 groups, Mann-Whitney test was used
      for qualitative variables and paired t test and repeated measure for quantitative
      variables with normal distribution. Statistical analysis was performed using SPSS
      16. All statistical references were made at ?=0.05. Results: Children's
      depression and manifest anxiety scores were not significantly different in the 2
      groups before the intervention; however, their changes immediately after
      intervention and at the 3- month follow-up were significant (p<0.001). Moreover,
      hyperactivity (p = 0.039), peer problems (p = 0.011), and parental depression (p
      = 0.015) scores significantly changed in both groups over time. Conclusion:
      Implementation of Friends for Life program is effective in prevention and
      treatment of the symptoms of anxiety and depression in children.

PMID- 29472955
TI  - Improving Depression, and Quality of Life in Patients with Type 2 Diabetes: Using
      Group Cognitive Behavior Therapy.
AB  - Objective: Depression is a chronic condition comorbid with diabetes type 2 that
      often remains untreated. Dealing with diabetes is a challenging task for patients
      and can lead to depression in long term. These two conditions have a negative
      influence on each other and on the individual's quality of life. The purpose of
      this study was to investigate the effect of group cognitive behavior therapy on
      depression, quality of life in women with diabetes type 2. Method: We conducted a
      clinical trial among 30 women with diabetes type 2 comorbid with depression. The
      women were divided randomly into the two groups of intervention and control. Each
      group consisted of 15 individuals. The intervention group received 10 sessions of
      group cognitive behavior therapy while the control group didn't. Results: The
      results suggested that group cognitive-behavior therapy decreased depression
      symptoms (F=72.17, p<0.001), and improved quality of life of the patients
      (F=8.82, p<0.05) of the intervention group compared to the control group.
      Conclusion: The results shows that group cognitive behavior therapy can affect
      depression symptoms, and consequently patients' quality of life with diabetes
      type 2.

PMID- 29472956
TI  - Adherence to Guideline Recommendations in Patients with Thyroid Nodules.
AB  - Introduction: Thyroid nodules are common and fine-needle aspiration (FNA) biopsy
      is the standard of care for work-up to exclude thyroid cancer. In this study, we
      examined the discrepancy between daily practice and recommended diagnostic
      approach for management of thyroid nodules, based on history taking, laboratory,
      and imaging studies. Methods: This was a retrospective chart review of 199
      patients who had ultrasound-guided fine needle aspiration (UGFNA) performed at a
      Midwest academic medical center from January 2010 to December 2011. The quality
      measures were selected based on recommended clinical practice guidelines,
      including family history, history of neck radiation, neck symptoms, TSH test, and
      thyroid ultrasound. Results: The majority of patients were Caucasian females.
      Family history of thyroid cancer and childhood neck radiation exposure were
      documented in 79 subjects (40%) and 76 subjects (38%), respectively. Neck
      symptoms were documented in most subjects, including dysphonia (56.8%), dysphagia
      (69.9%), and dyspnea (41.2%). Most subjects had a TSH measured and an ultrasound
      performed prior to biopsy (75% and 86%, respectively). Conclusions: It appears
      there is a gap between current patient care and clinical practice guidelines for
      management of thyroid nodules. Clinical history and ultrasound features for risk
      stratification of UGFNA were lacking, which could reflect physicians'
      unfamiliarity with the guidelines. As thyroid nodules are common, enhancing
      knowledge of the current guidelines could improve appropriate work-up. Further
      studies are needed to identify factors associated with the poor compliance with
      clinical guidelines in management of thyroid nodules.

PMID- 29472957
TI  - Direct Primary Care in 2015: A Survey with Selected Comparisons to 2005 Survey
      Data.
AB  - Introduction: Direct primary care (DPC), a fee for membership type of practice,
      is an evolving innovative primary care delivery model. Little is known about
      current membership fees, insurance billing status, physician training, and
      patient panel size in DPC practices. This study aimed to obtain current data for
      these variables, as well as additional demographic and financial indicators, and
      relate the findings to the Healthy People 2020 goals. It was predicted that DPC
      practices would (1) submit fewer claims to insurance, (2) have decreased
      membership fees, (3) be primarily family medicine trained, and (4) have increased
      the projected patient panel size since 2005. Methods: An electronic survey was
      sent to DPC practices (n = 65) requesting location, membership fees, projected
      patient panel size, insurance billing status, training, and other demographic and
      financial indicators. Data were aggregated, reported anonymously, and compared to
      two prior characterizations of DPC practices done in 2005. Results: Thirty-eight
      of 65 (59%) practices responded to the 2015 survey. The majority of respondents
      (84%) reported using an EMR, offering physician email access (82%), 24-hour
      access (76%), same day appointments (92%), and wholesale labs (74%). Few
      respondents offered inpatient care (16%), obstetrics (3%), or financial/insurance
      consultant services. Eighty-eight percent (88%) of practices reported annual
      individual adult membership rates between $500 and $1,499, decreased from 2005
      where 81% reported greater than a $1,500 annual fee. The proportion of practices
      who submit bills to insurance decreased from 75% in 2005 to 11% in 2015. Fifty
      six percent (56%) of practices reported projected patient panel size to be
      greater than 600, increased from 40% in 2005. Family medicine physicians
      represented 87% of respondents, markedly different from 2005 when 62 - 77% of DPC
      respondents were general internal medicine physicians. Conclusions: Most DPC
      practices no longer submit to insurance and are family medicine trained. Compared
      with the previous sampling, DPC practices report decreased membership fees and
      increased projected panel size. These trends may signify the DPC movement's
      growth in application and scope.

PMID- 29472958
TI  - An Evaluation of SmokeFree for Kansas Kids: An Intervention to Promote Tobacco
      Cessation in Pediatric Clinics.
AB  - Introduction: Smokefree for Kansas Kids is a program designed to train pediatric
      clinic staff to assess for tobacco exposure and provide brief smoking cessation
      interventions to caregivers and patients. The purpose of this study was to
      evaluate the impact of this program and improve future tobacco intervention
      efforts in pediatric clinics. Method: Eighty-six pediatric physicians and staff
      attended at least one of three training sessions. A random sample of pediatric
      medical records was selected pre-intervention (n = 49) and post-intervention (n =
      150). Electronic medical records were reviewed to assess for documentation of
      tobacco use intervention implemented in the clinic. Results: Of the 199 pediatric
      clinic visits reviewed, 197 met the study criteria. All but one visit documented
      an assessment of tobacco exposure. Among children exposed to tobacco (n = 42),
      providers were more likely to discuss tobacco use with caregivers post
      intervention (35.7%) compared to pre-intervention (7.1%; p < 0.05). One in five
      caregivers in the post-intervention group were advised to quit (21.4%) compared
      to the pre-intervention group (7.1%). In the post-intervention group, 14.3% were
      referred to the state quitline compared to no referrals in the pre-intervention
      group. The difference in rates for providing advice and referral between pre
      intervention and post-intervention were not statistically significant.
      Conclusions: Implementation of the Smoke Free for Kansas Kids intervention was
      associated with modest improvements in clinic tobacco intervention efforts, but
      many patients still failed to receive optimal assessments or interventions.
      Additional efforts may be needed to enhance this program.

PMID- 29472959
TI  - Successes and Challenges of Optimal Trauma Care for Rural Family Physicians in
      Kansas.
AB  - Introduction: Kansas has a regionalized trauma system with formal mechanisms for
      review, however, increased communication with rural providers can uncover
      opportunities for system process improvement. Therefore, this qualitative study
      explored perceptions of family medicine physicians staffing emergency departments
      (ED) in rural areas, specifically to determine what is going well and what areas
      needed improvement in relation to the trauma system. Methods: A focus group
      included Kansas rural family physicians recruited from a local symposium for
      family medicine physicians. Demographic information was collected via survey
      prior to the focus group session, which was audiotaped. Research team members
      read the transcription, identified themes, and grouped the findings into
      categories for analysis. Results: Seven rural family medicine physicians
      participated in the focus group. The majority were male (71%) with the mean age
      46.71 years. All saw patients in the ED and had treated injuries due to
      agriculture, falls, and motor vehicle collisions. Participants identified
      successes in the adoption and enforcement of standardized processes, specifically
      through level IV trauma center certification and staff requirements for Advanced
      Trauma Life Support training. Communication breakdown during patient discharge
      and skill maintenance were the most prevalent challenges. Conclusions: Even with
      an established regionalized trauma system in the state of Kansas, there continues
      to be opportunities for improvement. The challenges acknowledged by focus group
      participants may not be identified through patient case reviews (if conducted),
      therefore tertiary centers should conduct system reviews with referring hospitals
      regularly to improve systemic concerns.

PMID- 29472960
TI  - Longitudinally Extensive Spinal Neurosarcoid from the Brainstem to T3 - T4.

PMID- 29472961
TI  - Primary Cutaneous Nocardiosis in a Patient Taking Adalimumab Therapy for Crohn's
      Disease.

PMID- 29472962
TI  - Preparing Medical Students for the Medical Interview.

PMID- 29472963
TI  - The Relationship of Personality Style and Attention Deficit Hyperactivity
      Disorder in Children.
AB  - Introduction: This study was to identify personality correlates of children with
      a diagnosis of Attention Deficit Hyperactive Disorder (ADHD). The Jungian
      Personality Type dimensions primarily considered were Sensing/Intuiting and
      Perceiving/Judging. A Sensing child is likely to be very present-centered. A
      Perceiving child tends to be curious and resist order and structure. Methods:
      Children attending a general pediatric clinic with a diagnosis of ADHD were
      eligible to participate. Enrolled children were administered the Murphy-Meisgeier
      Type Indicator for Children. Binomial tests were performed comparing Perceiving
      and Sensing personality components to accepted population rates. Results:
      Participants (n = 117) were predominantly male (78%) with a median age of 10
      years. The Sensing trait (72%) was more prevalent than expected, though
      prevalence for the Perceiving trait (44%) did not differ from population rates.
      Conclusion: Personality types occasioned with the diagnosis of ADHD could be
      useful in establishing/normalizing treatment regimens and approaches to assist
      these children and their families better.

PMID- 29472964
TI  - Functional Outcomes of Thoracolumbar Junction Spine Fractures.
AB  - Introduction: Few studies have evaluated the functional outcomes of traumatic
      thoracic and lumbar vertebral body fractures. This study evaluated the functional
      and clinical outcomes of patients, who sustained a fracture to the thoracolumbar
      area of the spine (T10 to L2 region), with >= 25 degrees  kyphosis versus those
      with less kyphotic curvature. Methods: The trauma registry records of two level 1
      trauma centers using ICD-9 codes for fracture to the thoracolumbar juncture (T10
      to L2 region) were reviewed. Kyphosis angle was measured on the standing lateral
      thoracolumbar (T1 - L5) radiograph at initial trauma and at clinical follow-up.
      Functional outcome questionnaires, including the Oswestry Disability
      Questionnaire (ODQ), the Roland Morris Disability Questionnaire (RMDQ), and the
      Nottingham Health Profile (NHP), were evaluated at clinical follow-up. Work
      status and medication used after trauma also were recorded. Results: A total of
      38 patients met the inclusive criteria. Seventeen patients (45%) had >= 25
      degrees  kyphosis and 21 patients (55%) had < 25 degrees  kyphosis at follow-up.
      These two groups were similar based on sex and age. Based on the ODQ Score, the
      RMDQ Score, and the NHP, no statistically significant differences were detected
      between the two groups in regards to energy, pain, mobility, emotional reaction,
      social isolation, and sleep. Conclusions: Patients who sustained a fracture to
      the thoracolumbar area of the spine with >= 25 degrees  kyphosis do not report
      worse clinical outcomes. When using the kyphosis angle as an indication for
      surgery, it should be used with caution and not exclusively.

PMID- 29472965
TI  - Validation of Different Combination of Three Reversing Half-Hitches Alternating
      Posts (RHAPs) Effects on Arthroscopic Knot Integrity.
AB  - Introduction: With arthroscopic techniques being used, the importance of knot
      tying has been examined. Previous literature has examined the use of reversing
      half-hitches on alternating posts (RHAPs) on knot security. Separately, there has
      been research regarding different suture materials commonly used in the operating
      room. The specific aim of this study was to validate the effect of different
      stacked half-hitch configuration and different braided suture materials on
      arthroscopic knot integrity. Methods: Three different suture materials tied with
      five different RHAPs in arthroscopic knots were compared. A single load-to
      failure test was performed and the mean ultimate clinical failure load was
      obtained. Results: Significant knot holding strength improvement was found when
      one half-hitch was reversed as compared to baseline knot. When two of the half
      hitches were reversed, there was a greater improvement with all knots having a
      mean ultimate clinical failure load greater than 150 newtons (N). Comparison of
      the suture materials demonstrated a higher mean ultimate clinical failure load
      when Force Fiber(r) was used and at least one half-hitch was reversed. Knots tied
      with either Force Fiber(r) or Orthocord(r) showed 0% chance of knot slippage
      while knots tied with FiberWire(r) or braided fishing line had about 10 and 30%
      knot slippage chances, respectively. Conclusions: A significant effect was
      observed in regards to both stacked half-hitch configuration and suture materials
      used on knot loop and knot security. Caution should be used with tying three
      RHAPs in arthroscopic surgery, particularly with a standard knot pusher and
      arthroscopic cannulas. The findings of this study indicated the importance of
      three RHAPs in performing arthroscopic knot tying and provided evidence regarding
      discrepancies of maximum clinical failure loads observed between orthopaedic
      surgeons, thereby leading to better surgical outcomes in the future.

PMID- 29472966
TI  - A Preliminary Study of the Attitudes and Barriers of Family Physicians to
      Prescribing HIV Preexposure Prophylaxis.
AB  - Introduction: Attitudes of individuals who provide HIV care towards prescribing
      Preexposure Prophylaxis (PrEP) to at-risk populations have been studied, but few
      studies indicate if family physicians would be willing to prescribe PrEP as most
      family physicians do not specialize in HIV medicine. Few data exist on the
      perceived barriers preventing family physicians from prescribing PrEP. The
      purpose of this project was to assess the attitudes and perceived barriers of
      family physicians in Kansas towards prescribing PrEP to high risk patient
      populations. Methods: This study was a descriptive, observational, and cross
      sectional survey of family physicians who respond to email surveys issued through
      the Family Medicine Research and Data Information Office (FM RADIO). Results:
      Fifty-three percent of family physicians take a sexual history on new patients
      less than frequently, and only 35% frequently ask about the use of safe sex
      practices. Only 29% frequently ask if the patient has sex with men, women, or
      both. Seventy-six percent of respondents would be willing to prescribe PrEP to
      men who have sex with men, and an equal percentage would be willing to prescribe
      to heterosexually active men and women who are at substantial risk of acquiring
      HIV. While 59% of participants agreed that PrEP belongs in the primary care
      domain of treatment, 71% agreed that they had limited or no knowledge of PrEP
      guidelines. Conclusions: This preliminary study indicated a need for increased
      family physician screening of new patients for high risk sexual behaviors who
      would be eligible for PrEP. The limited knowledge of PrEP guidelines and its use
      in clinical practice are significant limiting factors to increasing prescribing
      practices in the family medicine community rather than a perceived ethical
      dilemma of prescribing PrEP to men who have sex with men. As a result, an
      increase in continuing medical education about PrEP could significantly increase
      its prescribing in the family medicine community.

PMID- 29472967
TI  - Pulmonary Embolism after Arthroscopic Bankart and Rotator Cuff Repair.

PMID- 29472968
TI  - Hydroxyurea-Induced Interstitial Pneumonitis: A Rare Clinical Entity.

PMID- 29472969
TI  - Student Expenses in Residency Interviewing.
AB  - Background: The student costs of residency interviewing are of increasing concern
      but limited current information is available. Updated, more detailed information
      would assist students and residency programs in decisions about residency
      selection. The study objective was to measure the expenses and time spent in
      residency interviewing by the 2016 graduating class of the University of Kansas
      School of Medicine and assess the impact of gender, regional campus location, and
      primary care application. Methods: All 195 students who participated in the 2016
      National Residency Matching Program (NRMP) received a 33 item questionnaire
      addressing interviewing activity, expenses incurred, time invested and related
      factors. Main measures were self-reported estimates of expenses and time spent
      interviewing. Descriptive analyses were applied to participant characteristics
      and responses. Multivariate analysis of variance (MANOVA) and chi-square tests
      compared students by gender, campus (main/regional), and primary care/other
      specialties. Analyses of variance (ANOVA) on the dependent variables provided
      follow-up tests on significant MANOVA results. Results: A total of 163 students
      (84%) completed the survey. The average student reported 38 (1-124) applications,
      16 (1-54) invitations, 11 (1-28) completed interviews, and spent $3,500 ($20
      $12,000) and 26 (1-90) days interviewing. No significant differences were found
      by gender. After MANOVA and ANOVA analyses, non-primary care applicants reported
      significantly more applications, interviews, and expenditures, but less program
      financial support. Regional campus students reported significantly fewer
      invitations, interviews, and days interviewing, but equivalent costs when
      controlled for primary care application. Cost was a limiting factor in accepting
      interviews for 63% and time for 53% of study respondents. Conclusions: Students
      reported investing significant time and money in interviewing. After controlling
      for other variables, primary care was associated with significantly lowered
      expenses. Regional campus location was associated with fewer interviews and less
      time interviewing. Gender had no significant impact on any aspect studied.

PMID- 29472970
TI  - Comparisons of Medical Student Knowledge Regarding Life-Threatening CT Images
      Before and After Clinical Experience.
AB  - Background: Currently, no national standard exists for educating medical students
      regarding radiography or formal research indicating the level of improvement
      regarding computed tomography (CT) interpretation of medical students during
      clinical rotations. Methods: Students were evaluated based on their response to
      twenty-two open-ended questions regarding diagnosis and treatment of eleven de
      identified CT images of life-threatening injuries. The number of incorrect
      answers was compared with correct or partially correct answers between students
      starting third-year clinical rotations and those starting their fourth year.
      Results: Survey results were collected from 65 of 65 (100%) beginning third-year
      students and 9 of 60 (15%) beginning fourth-year students. Students in their
      fourth-year had less incorrect answers compared to third-year students, with five
      questions reflecting a statistically significant reduction in incorrect
      responses. The image with the least incorrect for both groups was epidural
      hemorrhage, 33.9% and 18.5% incorrect for third-year students for diagnosis and
      treatment, respectively, and 11.1% and 0% incorrect for fourth-year students.
      Outside of this image, the range of incorrect answers for third-year students was
      75.4% to 100% and 44.4% to 100% for fourth-year students. Conclusion: Baseline CT
      knowledge of medical students, regardless of clinical experience, indicated a
      strong deficit, as more students were incorrect than correct for the majority of
      CT images.

PMID- 29472971
TI  - Safe Sleep Knowledge and Use of Provided Cribs in a Crib Delivery Program.
AB  - Background: Risk of infant sleep-related death can be reduced through safe sleep
      practices. Barriers to infant safe sleep have been mitigated through education
      and crib distribution, however, previous studies have not explored whether
      distributed cribs are put to use. Methods: In a rural Michigan county, the Great
      Start Sleep Initiative supplied cribs and education shortly after infant birth to
      families with high-risk of infant mortality, as assessed through comprehensive
      interviews with families by program staff. Participant knowledge was evaluated
      using structured pre- and post-assessments before and after education. Further, a
      home visit was conducted to evaluate the infant's sleeping environment. Data from
      the program, collected between January 2012 and December 2014, was evaluated.
      Results: Cribs and concomitant education were delivered to 75 caregivers.
      Knowledge of safe sleep practices increased significantly at follow-up with 67
      caregivers (89%) affirming back positioning, 68 (91%) endorsing removal of unsafe
      items or soft objects, such as blankets, from the sleeping area, and 42 (56%)
      renouncing bed-sharing. At the home visit, 74 caregivers (99%) were using a crib
      to put their infant down to sleep, 70 (93%) were using the provided crib, and 67
      (89%) had no unsafe items in the child's sleeping area. Conclusions: Providing
      education to high-risk mothers resulted in improved safe sleep knowledge and
      provided cribs are used in these homes.

PMID- 29472972
TI  - Bone Health Improvement Protocol.
AB  - Introduction: Metabolic bone disease is a malady that causes significant
      morbidity and mortality to a patient who has sustained a fragility fracture.
      There is currently no protocol to prevent secondary fragility fracture at our
      institution. The objective of this study was to create an appropriate protocol
      for implementing clinical pathways for physicians to diagnose and treat
      osteoporosis and fragility fractures by educating patients. Methods: A
      multidisciplinary team created an appropriate protocol that could be implemented
      in an inpatient setting. A thorough literature review was conducted to evaluate
      potential barriers and efficacious methods of protocol design. Results: A bone
      health improvement protocol was developed. Any patient over the age of 50 who
      sustains a fracture from low energy trauma, such as a fall from standing or less,
      should be considered to place into this protocol. These patients received
      education on metabolic bone disease, a prescription for high dose vitamin D
      therapy, and laboratory testing to determine the etiology of their metabolic bone
      disease. Continuity of care of these patients with their primary care provider
      was provided for further management of their metabolic bone disease and
      evaluation of their disease after discharged from the hospital. Discussion:
      Comprehensive secondary prevention should consist of osteoporosis assessment and
      treatment together with a fall risk assessment. With this protocol, secondary
      fragility fractures potentially could be prevented.

PMID- 29472973
TI  - The Use of Precision Alignment Technology to Circumvent Patient-Specific
      Roadblocks in Performing Total Knee Arthroplasty: A Case Series.

PMID- 29472974
TI  - Congenital Coronary Artery Anomaly in an Asymptomatic Patient Presenting with
      Cardiac Arrest.

PMID- 29472975
TI  - Contralateral Pneumothorax after the Implantation of a Dual Chamber Pacemaker.

PMID- 29472976
TI  - A Survey of Safety Recommendations for All-Terrain Vehicle Dealers and Track
      Owners in Kansas.
AB  - Introduction: All-terrain vehicles (ATVs) are associated with injury, mortality,
      and healthcare costs. ATV related injuries are less severe when consistent safety
      practices are followed, however, ATV safety regulations are varied among states.
      This study sought to survey Kansas ATV dealers and track owners to determine
      safety promotion practices. Methods: A cross-sectional telephone survey was
      conducted of Kansas ATV dealers and tracks. Survey questions included promotion
      and sale of safety equipment, provision of ATV safety information, and respondent
      characteristics. Results: Of those contacted, 32% of dealers and 31% of tracks
      responded to the survey. Most ATV dealers sell safety gear (70% - 100%) and all
      recommend safety gear to buyers and riders. All ATV tracks reported requiring
      helmets (100%) but were varied regarding other forms of safety gear. The majority
      of ATV dealers (77%) recommended safety courses, but only 31% of dealers and 40%
      of tracks offered courses. Eighty percent of ATV tracks and 52% of dealers felt
      they had a professional responsibility to educate riders/owners on safety.
      Conclusion: Safety promotion by ATV dealers in Kansas consistently was
      recommended, but often limited to the sales of safety gear (helmets and gloves)
      or the provision of manufacturer provided safety materials. Further, ATV dealers
      reported rarely offering skills tests or safety courses to buyers. In Kansas,
      safety promotion at the point of sale or track level could be improved to
      increase public awareness of ATV safety practices.

PMID- 29472977
TI  - Rural Kansas Family Physician Satisfaction with Caring for Spanish-Speaking Only
      Patients.
AB  - BACKGROUND: Patient satisfaction with the care they receive can be influenced
      negatively by a language barrier between the physician and patient. However,
      there is a paucity of information regarding the consequences of a language
      barrier on physician satisfaction, although this barrier has the potential to
      decrease physician wellness. This study sought to determine if a language barrier
      is a source of professional dissatisfaction in family medicine physicians in
      rural Kansas. METHODS: In a cross-sectional study, members of the Kansas Academy
      of Family Physicians who practiced in the rural Kansas counties with the highest
      percentage of Hispanic residents were surveyed. A questionnaire was developed to
      determine the demographics of the physician, details regarding his or her
      practice, and percentage of Hispanic and Spanish-speaking only (SSO) patients in
      their practice. Physicians also were queried as to their level of Spanish
      speaking ability, availability of certified interpreters, and their satisfaction
      with caring for their SSO patients. RESULTS: Fifty-two physicians were identified
      and sent questionnaires by mail. Eighteen questionnaires were completed and
      returned, resulting in a 34% response rate. Respondents remained anonymous. In
      the practices surveyed, 61% of practice settings had a Hispanic-patient
      population greater than 25%. Only one of the eighteen respondents had greater
      than 25% of SSO patients in his or her practice. A certified interpreter was used
      less than 25% of the time in over 75% of the clinical encounters with SSO
      patients. Seventy-five percent of physicians reported no difficulty establishing
      trust and rapport with their SSO patients. Eighty-nine percent of respondents
      rated their relationship with SSO patients as good to excellent, and 83% were
      satisfied with the care they were able to provide this group. Seventy-eight
      percent of respondents reported that their ability to care for SSO patients
      decreased or had no effect on their professional satisfaction. Seventy-eight
      percent of physicians also rated their overall professional satisfaction in
      regards to their physician/patient relationship as good to excellent. However,
      language barriers affected physician-patient relationships, physician
      satisfaction with care, and professional satisfaction. CONCLUSION: Language
      barrier affected physician's relationships with SSO patients, led to decreased
      physician satisfaction with the care they provided and to decreased professional
      satisfaction.

PMID- 29472978
TI  - Kansas Provider Report of Adolescent Vaccinations in Their Practice.
AB  - Background: Kansas falls consistently below average for adolescent vaccination of
      meningococcal (MCV), human papillomavirus (HPV), and influenza. Methods: For this
      study, the members of Kansas Chapter of the American Academy of Pediatrics were
      emailed a confidential electronic survey soliciting their impressions of
      vaccination in their practice. Results: Of 137 providers emailed, 61 (45%)
      completed the survey. Thirteen providers were excluded as they did not
      see/vaccinate adolescents or did not complete the survey. Tetanus, diphtheria,
      pertussis (Tdap), and MCV vaccines were most commonly up to date with 31 (65%)
      and 20 (42%) respondents reporting greater than 90% immunization rates,
      respectively. HPV (n = 42, 89%) and influenza (n = 40, 83%) vaccines had refusal
      rates greater than 25% in most clinics. Most practices (n = 44, 92%) used
      internal electronic medical records to track vaccinations, although 29 practices
      (60%) utilized the state immunization information system. Providers requested
      vaccine-specific patient education tools, positive media coverage, staffing
      support, and best-practices workshops to support vaccination efforts. Conclusion:
      Kansas providers may not be optimizing available resources to enhance these
      rates, such as Web IZ tracking and immunization reminders. Patient education
      supplies, specific to HPV and Influenza vaccination, potentially could increase
      vaccination rates.

PMID- 29472979
TI  - Barriers to Utilizing Medicaid Smoking Cessation Benefits.
AB  - Introduction: Smoking is the number one preventable cause of death in the United
      States. Under the Affordable Care Act, Kansas Medicaid covers all seven FDA
      approved smoking cessation therapies. However, it is estimated only 3% of Kansas
      Medicaid smokers use treatment compared to the national estimate of 10%. The
      objective is to determine systemic barriers in place that prevent optimal
      utilization of Medicaid smoking cessation benefits among KU Medical Center
      Internal Medicine patients. Methods: For this quality improvement project, a
      population of 169 Kansas Medicaid smokers was identified who had been seen at the
      KU Internal Medicine Clinic from January 1, 2015 - February 16, 2016. Phone
      surveys were completed with 62 individuals about smoking status, interest in
      using smoking cessation treatment options, and awareness of Medicaid coverage of
      treatment. Results: Of the 62 respondents, 24 (39%) were prescribed
      pharmacotherapy and 41 (66%) were interested in using smoking cessation
      treatment. There were eight who had quit smoking. Of the remaining 54 smokers, 31
      (57%) were unaware that Medicaid would cover pharmacotherapy. Of 24 participants
      who received a prescription for pharmacotherapy, 13 (54%) were able to fill the
      prescription at no cost using the Medicaid benefit. Conclusions: The majority of
      respondents were interested in using smoking cessation treatment yet three main
      barriers existed to using Medicaid smoking cessation benefits: physicians not
      prescribing treatment to patients, patients not aware of Medicaid coverage, and
      inadequate pharmacy filling. Improved physician and patient awareness of Medicaid
      coverage will facilitate more patients receiving smoking cessation therapy and
      ultimately quitting smoking.

PMID- 29472980
TI  - Pediatric Farm Injuries: Morbidity and Mortality.
AB  - Background: Agriculture is an industry where family members often live and work
      on the same premises. This study evaluated injury patterns and outcomes in
      children from farm-related accidents. Methods: A 10-year retrospective review of
      farm-accident related injuries was conducted of patients 17 years and younger.
      Data collected included demographics, injury mechanism, accident details, injury
      severity and patterns, treatments required, hospitalization details, and
      discharge disposition. Results: Sixty-five patients were included; 58.5% were
      male and the mean age was 9.7 years. Median Injury Severity Score and Glasgow
      Coma Scale were 5 and 15, respectively. Accident mechanisms included animal
      related (43.1%), fall (21.5%), and motor vehicle (21.5%). Soft tissue injuries,
      concussions and upper extremity fractures were the most common injuries observed
      (58.5%, 29.2%, and 26.2%, respectively). Twenty-six patients (40%) required
      surgical intervention. Mean hospital length of stay was 3.4 +/- 4.7 days. The
      majority of patients were discharged to home (n = 62, 95.4%) and two patients
      suffered permanent disability. Conclusions: Overall, outcomes for this population
      were favorable, but additional measures to increase safety, such as fall
      prevention, animal handling, and driver safety training should be advocated.

PMID- 29472981
TI  - The State of Diabetes in Kansas: A Community Centered Approach to the Treatment
      of Diverse Populations.

PMID- 29472982
TI  - Big data, smart cities and city planning.
AB  - I define big data with respect to its size but pay particular attention to the
      fact that the data I am referring to is urban data, that is, data for cities that
      are invariably tagged to space and time. I argue that this sort of data are
      largely being streamed from sensors, and this represents a sea change in the
      kinds of data that we have about what happens where and when in cities. I
      describe how the growth of big data is shifting the emphasis from longer term
      strategic planning to short-term thinking about how cities function and can be
      managed, although with the possibility that over much longer periods of time,
      this kind of big data will become a source for information about every time
      horizon. By way of conclusion, I illustrate the need for new theory and analysis
      with respect to 6 months of smart travel card data of individual trips on Greater
      London's public transport systems.

PMID- 29472984
TI  - Factors influencing prospective mother with prenatal qualified doctor care among
      the reproductive women in Bangladesh.
AB  - Maternal and child mortality are the key indicators of health and development of
      the country. Maternal and child health are interconnected to prenatal care.
      Consulting a doctor at the prenatal stage will not only ensure mother's and her
      unborn babies' safety, but also has a great influence to reduce the maternal and
      infant mortality. In this paper, an attempt has been made to analyze the status
      of prenatal care provided by the qualified doctor among pregnant mothers in
      Bangladesh. Data and required information of 8793 reproductive women were
      collected from the Bangladesh Demographic and Health Survey (BDHS) 2014. Logistic
      regression model has been used to identify the most significant determinants of
      the prenatal doctor visits. In this research, it is found that prenatal cares by
      a qualified doctor during pregnancy depend on several social and demographic
      characteristics of a woman. It is observed that women staying both urban and
      rural areas have similar behaviour of caring regarding their pregnancy related
      complications. Beside this Respondent's age, education, her husband's education
      and the number of ever born children have significant contribution on prenatal
      doctor visit. On the other hand, division, religion, husband's desire for
      children has no effect on it. Overall the model is able to predict 71.65% women
      into their appropriate group based on these factors.

PMID- 29472985
TI  - Rituximab: a novel treatment for refractory Riedel's thyroiditis.
AB  - : This case report reviews the rare condition of Riedel's thyroiditis via a
      patient case. The report highlights the difficulties that one may encounter when
      managing such a case in regards to patient symptoms, side effects of medications
      and the relapsing nature of the condition. The case report also highlights novel
      treatment in the treatment of Riedel's thyroiditis, rituximab, how this works and
      the resolution of symptoms that we have achieved with our patient on this
      treatment. Learning points: Riedel's thyroiditis is characterised by chronic
      inflammation, which causes dense fibrosis in the thyroid gland.Riedel's
      thyroiditis can present with neck pain, dysphagia and dyspnoea with a firm, non
      tender mass found on examination.Riedel's thyroiditis is part of the IgG4-related
      systemic disorders.Rituximab is a monoclonal antibody that works against the
      protein CD20.

PMID- 29472986
TI  - Unusual AIP mutation and phenocopy in the family of a young patient with
      acromegalic gigantism.
AB  - : Early-onset acromegaly causing gigantism is often associated with aryl
      hydrocarbon-interacting receptor protein (AIP) mutation, especially if there is a
      positive family history. A15y male presented with tiredness and visual problems.
      He was 201 cm tall with a span of 217 cm. He had typical facial features of
      acromegaly, elevated IGF-1, secondary hypogonadism and a large macroadenoma. His
      paternal aunt had a history of acromegaly presenting at the age of 35 years.
      Following transsphenoidal surgery, his IGF-1 normalized and clinical symptoms
      improved. He was found to have a novel AIP mutation destroying the stop codon
      c.991T>C; p.*331R. Unexpectedly, his father and paternal aunt were negative for
      this mutation while his mother and older sister were unaffected carriers,
      suggesting that his aunt represents a phenocopy. Learning points: Typical
      presentation for a patient with AIP mutation with excess growth and eunuchoid
      proportions.Unusual, previously not described AIP variant with loss of the stop
      codon.Phenocopy may occur in families with a disease-causing germline mutation.

PMID- 29225776
TI  - The sedentary (r)evolution: Have we lost our metabolic flexibility?
AB  - During the course of evolution, up until the agricultural revolution,
      environmental fluctuations forced the human species to develop a flexible
      metabolism in order to adapt its energy needs to various climate, seasonal and
      vegetation conditions. Metabolic flexibility safeguarded human survival
      independent of food availability. In modern times, humans switched their primal
      lifestyle towards a constant availability of energy-dense, yet often nutrient
      deficient, foods, persistent psycho-emotional stressors and a lack of exercise.
      As a result, humans progressively gain metabolic disorders, such as the metabolic
      syndrome, type 2 diabetes, non-alcoholic fatty liver disease, certain types of
      cancer, cardiovascular disease and Alzheimer's disease, wherever the sedentary
      lifestyle spreads in the world. For more than 2.5 million years, our capability
      to store fat for times of food shortage was an outstanding survival advantage.
      Nowadays, the same survival strategy in a completely altered surrounding is
      responsible for a constant accumulation of body fat. In this article, we argue
      that the metabolic disease epidemic is largely based on a deficit in metabolic
      flexibility. We hypothesize that the modern energetic inflexibility, typically
      displayed by symptoms of neuroglycopenia, can be reversed by re-cultivating
      suppressed metabolic programs, which became obsolete in an affluent environment,
      particularly the ability to easily switch to ketone body and fat oxidation. In a
      simplified model, the basic metabolic programs of humans' primal hunter-gatherer
      lifestyle are opposed to the current sedentary lifestyle. Those metabolic
      programs, which are chronically neglected in modern surroundings, are identified
      and conclusions for the prevention of chronic metabolic diseases are drawn.

PMID- 29472987
TI  - Adult female with symptomatic AVPR2-related nephrogenic syndrome of inappropriate
      antidiuresis (NSIAD).
AB  - : Activating mutations in AVPR2 are associated with nephrogenic syndrome of
      inappropriate antidiuresis (NSIAD). NSIAD causes hyponatremia, decreased serum
      osmolality and clinical symptoms, which may present from birth or in infancy and
      include hypotonia, irritability, vomiting and/or seizures. Symptoms in later life
      are often less specific and include malaise, dizziness, confusion, tiredness and
      headache. NSIAD is a rare X-linked condition, which is associated with a variable
      phenotype in males, of whom some present in infancy but others do not become
      symptomatic until adulthood, or occasionally, never. Female carriers may present
      with episodes of hyponatremia, usually found incidentally. Literature in this
      field is limited; namely, two clinical reports describing a female proband, both
      diagnosed in infancy. We describe, for the first time, the case of an adult
      female proband with NSIAD, who had longstanding associated symptoms of tiredness,
      headache, temporary memory loss and mood changes as well as hyponatremia and
      decreased serum osmolality. A water load test demonstrated an inability to dilute
      urine and gene sequencing confirmed a recurrent activating mutation in AVPR2. The
      variant was inherited from the proband's mother who had had longstanding episodes
      of transient asymptomatic hyponatremia. This is the third report of a female
      proband with NSIAD and is the first female reported who sought medical treatment
      for chronic symptoms from adulthood. This case acts as a reminder of the
      importance of considering NSIAD as a diagnosis in females of all ages with
      unexplained hyponatremia. Learning points: Activating mutations in the AVPR2 gene
      are associated with the rare X-linked condition nephrogenic syndrome of
      inappropriate antidiuresis.NSIAD is associated with hyponatremia, decreased serum
      osmolality and inappropriately increased urinary osmolality. Early clinical
      symptoms in infancy include hypotonia, irritability, vomiting and/or seizures.
      Symptoms in later life include malaise, dizziness, confusion, tiredness and
      headache.NSIAD should be considered in female, as well as male, patients who
      present with unexplained hyponatremia and decreased serum osmolality. Family
      history may reveal relevant symptoms or biochemical features in other family
      members. However, family history may not always be informative due to the
      variable nature of the condition or if the proband has a de novo pathogenic
      variant.A water load test with measurement of AVP may be informative in
      distinguishing NSIAD from SIADH. Measurement of co-peptin levels may be
      considered, in substitution for direct measurement of AVP.Patients with NSIAD
      should be counseled about appropriate daily fluid volume intake. Potential
      episodes of fluid overload should be avoided.

PMID- 29472988
TI  - Mineralocorticoid hypertension and hypokalaemia induced by posaconazole.
AB  - : We describe severe hypokalaemia and hypertension due to a mineralocorticoid
      effect in a patient with myelodysplastic syndrome taking posaconazole as
      antifungal prophylaxis. Two distinct mechanisms due to posaconazole are
      identified: inhibition of 11beta hydroxylase leading to the accumulation of the
      mineralocorticoid hormone 11-deoxycorticosterone (DOC) and secondly, inhibition
      of 11beta hydroxysteroid dehydrogenase type 2 (11betaHSD2), as demonstrated by an
      elevated serum cortisol-to-cortisone ratio. The effects were ameliorated by
      spironolactone. We also suggest that posaconazole may cause cortisol
      insufficiency. Patients taking posaconazole should therefore be monitored for
      hypokalaemia, hypertension and symptoms of hypocortisolaemia, at the onset of
      treatment and on a monthly basis. Treatment with mineralocorticoid antagonists
      (spironolactone or eplerenone), supplementation of glucocorticoids (e.g.
      hydrocortisone) or dose reduction or cessation of posaconazole should all be
      considered as management strategies. Learning points: Combined hypertension and
      hypokalaemia are suggestive of mineralocorticoid excess; further investigation is
      appropriate.If serum aldosterone is suppressed, then further investigation to
      assess for an alternative mineralocorticoid is appropriate, potentially using
      urine steroid profiling and/or serum steroid panelling.Posaconazole can cause
      both hypokalaemia and hypertension, and we propose that this is due to two
      mechanisms - both 11beta hydroxylase inhibition and 11beta HSD2
      inhibition.Posaconazole treatment may lead to cortisol insufficiency, which may
      require treatment; however, in this clinical case, the effect was mild.First-line
      treatment of this presentation would likely be use of a mineralocorticoid
      antagonist.Patients taking posaconazole should be monitored for hypertension and
      hypokalaemia on initiation and monthly thereafter.

PMID- 29472989
TI  - Improving kNowledge Transfer to Efficaciously RAise the level of Contemporary
      Treatment in Heart Failure (INTERACT-in-HF): Study protocol of a mixed methods
      study.
AB  - Heart failure is a complex disease with poor outcome. This complexity may prevent
      care providers from covering all aspects of care. This could not only be relevant
      for individual patient care, but also for care organisation. Disease management
      programmes applying a multidisciplinary approach are recommended to improve heart
      failure care. However, there is a scarcity of research considering how disease
      management programme perform, in what form they should be offered, and what care
      and support patients and care providers would benefit most. Therefore, the
      Improving kNowledge Transfer to Efficaciously Raise the level of Contemporary
      Treatment in Heart Failure (INTERACT-in-HF) study aims to explore the current
      processes of heart failure care and to identify factors that may facilitate and
      factors that may hamper heart failure care and guideline adherence. Within a
      cross-sectional mixed method design in three regions of the North-West part of
      Europe, patients (n = 88) and their care providers (n = 59) were interviewed.
      Prior to the in-depth interviews, patients were asked to complete three
      questionnaires: The Dutch Heart Failure Knowledge scale, The European Heart
      Failure Self-care Behaviour Scale and The global health status and social
      economic status. In parallel, retrospective data based on records from these (n =
      88) and additional patients (n = 82) are reviewed. All interviews were audiotaped
      and transcribed verbatim for analysis.

PMID- 29472990
TI  - Differential Methylation of Syncytin-1 and 2 Distinguishes Fetal Growth
      Restriction from Physiologic Small for Gestational Age.
AB  - Objective  The retroviral genes encoding Syncytin-1 ( SYN1 ) and Syncytin-2 (
      SYN2 ) are epigenetically regulated, uniquely expressed in the placenta and
      critical to placental function. We sought to determine if placental expression
      and methylation patterns of SYN1 and SYN2 from pregnancies complicated by fetal
      growth restriction (FGR) differed from physiologic small for gestational age
      (SGA) and appropriate for gestational age (AGA) controls. Study Design  Placental
      biopsies were obtained from AGA, SGA and FGR neonates delivered at >36 weeks
      gestation. SGA and FGR were defined as birth weight <10% with FGR additionally
      requiring abnormal fetal testing. We quantified DNA methylation of SYN1 and SYN2
      by EpiTyper and gene expression by RT-qPCR. Results  We identified 10 AGA, 9 SGA
      and 7 FGR placentas. There was decreased methylation in SYN1 and SYN2 in FGR
      relative to AGA and SGA. When the sum of SYN1 and SYN2 methylation was used for
      prediction of FGR from SGA, the area under the receiver operator characteristic
      curve was 0.9048 (0.7602, 1). Conclusion   SYN1 and SYN2 methylation marks differ
      in FGR and SGA. We plan future studies to examine these markers in cell free DNA
      to determine if these methylation changes could be used as a biomarker for FGR.

PMID- 29472991
TI  - The axial skeleton of Poposaurus langstoni (Pseudosuchia: Poposauroidea) and its
      implications for accessory intervertebral articulation evolution in pseudosuchian
      archosaurs.
AB  - Dinosaurs and their close relatives grew to sizes larger than any other
      terrestrial animal in the history of life on Earth, and many enormous dinosaurs
      (e.g., Diplodocus, Spinosaurus, Tyrannosaurus) have accessory intervertebral
      articulations that have been suggested to support these large body sizes. Some
      pseudosuchian archosaurs have been reported to have these articulations as well,
      but few have been characterized in these taxa because of a lower abundance of
      complete, three-dimensional pseudosuchian vertebral material in relation to
      dinosaurs. We describe the axial column of the large (~4-5 m) poposauroid
      pseudosuchian Poposaurus langstoni from the Upper Triassic of Texas (TMM Locality
      31025 of the Otis Chalk localities; Dockum Group, Howard County, TX, USA). P.
      langstoni was originally named from pelvic girdle elements and vertebrae; here we
      describe newly discovered and prepared presacral vertebrae and a presacral rib
      from the original excavation of the holotype in the 1940s. The well-preserved
      vertebrae have well-defined vertebral laminae and clear hyposphene-hypantrum
      intervertebral articulations, character states mentioned in pseudosuchians but
      rarely described. The new material demonstrates variation present in the
      hyposphene-hypantrum articulation through the vertebral column. We compared these
      morphologies to other pseudosuchians with and without the hyposphene-hypantrum
      articulation. Based on these careful comparisons, we provide an explicit
      definition for the hyposphene-hypantrum articulation applicable across
      Archosauria. Within Pseudosuchia, we find the hyposphene-hypantrum appeared
      independently in the clade at least twice, but we also see the loss of these
      structures in clades that had them ancestrally. Furthermore, we found the
      presence of large body sizes (femoral lengths >~300 mm) and the presence of the
      hyposphene-hypantrum is correlated in most non-crocodylomorph pseudosuchian
      archosaurs with a few exceptions. This result suggests that the presence of the
      hyposphene-hypantrum is controlled by the increases and decreases in body size
      and not strictly inheritance.

PMID- 29472992
TI  - Different intensities of basketball drills affect jump shot accuracy of expert
      and junior players.
AB  - Background: In basketball a maximum accuracy at every game intensity is required
      while shooting. The aim of the present study was to investigate the acute effect
      of three different drill intensity simulation protocols on jump shot accuracy in
      expert and junior basketball players. Materials & Methods: Eleven expert players
      (age 26 +/- 6 yrs, weight 86 +/- 11 kg, height 192 +/- 8 cm) and ten junior
      players (age 18 +/- 1 yrs, weight 75 +/- 12 kg, height 184 +/- 9 cm) completed
      three series of twenty jump shots at three different levels of exertion. Counter
      Movement Jump (CMJ) height was also measured after each series of jump shots.
      Exertion's intensity was induced manipulating the basketball drills. Heart rate
      was measured for the whole duration of the tests while the rating of perceived
      exertion (RPE) was collected at the end of each series of shots. Results: Heart
      rate and rating of perceived exertion (RPE) were statistically different in the
      three conditions for both expert and junior players. CMJ height remained almost
      unchanged in both groups. Jump shot accuracy decreased with increasing drills
      intensity both in experts and junior players. Expert players showed higher
      accuracy than junior players for all the three levels of exertion (83% vs 64%, p
      < 0.001; 75% vs 57%, p < 0.05; 76% vs 60%, p < 0.01). Moreover, for the most
      demanding level of exertion, experts showed a higher accuracy in the last ten
      shots compared to the first ten shots (82% vs 70%, p < 0.05). Discussion: Experts
      coped better with the different exertion's intensities, thus maintaining a higher
      level of performance. The introduction of technical short bouts of high-intensity
      sport-specific exercises into skill sessions should be proposed to improve jump
      shot accuracy during matches.

PMID- 29472993
TI  - Life histories predict genetic diversity and population structure within three
      species of octopus targeted by small-scale fisheries in Northwest Mexico.
AB  - The fishery for octopus in Northwest Mexico has increased to over 2,000 tons
      annually, but to date the specific composition of the catch has been ignored.
      With at least three main species targeted by artisanal fisheries in the region
      with distinct life histories, the lack of basic biological information about the
      distribution, metapopulation size and structure of each species could impede
      effective fisheries management to avoid overexploitation. We tested if different
      life histories of three species of octopus could help predict observed patterns
      of genetic diversity, population dynamics, structure and connectivity and how
      this information could be relevant to the sustainable management of the fishery.
      We sequenced two mitochondrial genes and genotyped seven nuclear microsatellite
      loci to identify the distribution of each species in 20 locations from the Gulf
      of California and the west coast of the Baja California peninsula. We tested five
      hypotheses derived from population genetic theory based on differences in the
      fecundity and dispersal potential for each species. We discovered that Octopus
      bimaculoides with low fecundity and direct development (without a planktonic
      phase) had lower average effective population size and genetic diversity, but
      higher levels of kinship, population structure, and richness of private alleles,
      than the other two species. These features indicated limited dispersal and high
      local recruitment. In contrast, O. bimaculatus and O. hubbsorum with higher
      fecundity and planktonic phase as paralarvae had higher effective population size
      and genetic diversity, and overall lower kinship and population structure than O.
      bimaculoides. These observations supported higher levels of gene flow over a
      larger geographical scale. O. bimaculatus with the longest planktonic paralarval
      duration and therefore larger dispersal potential had differences in the
      calculated parameters possibly associated with increased connectivity. We propose
      O. bimaculoides is more susceptible to over exploitation of small, isolated
      populations and could have longer recovery times than the other two species. This
      species may benefit from distinct fishery management within each local
      population. O. bimaculatus and O. hubbsorum may benefit from fishery management
      that takes into account metapopulation structure over larger geographic scales
      and the directionality and magnitude of larval dispersal driven by ocean currents
      and population connectivity among individuals of each locality. The distribution
      of each species and variations in their reproductive phenology is also important
      to consider when establishing marine reserves or seasonal fishing closures.

PMID- 29472994
TI  - Seroprevalence of hepatitis B virus in Taiwan 30 years after the commencement of
      the national vaccination program.
AB  - Background: In this study, the long-term efficacy of hepatitis B virus (HBV)
      vaccination was assessed using seroprevalence and an age-period-cohort (APC)
      model of HBV seromarkers among university entrants 30 years after the
      introduction of the national neonatal HBV vaccination program in Taiwan. Methods:
      In total, data of 17,611 university entrants who underwent university entrance
      health examinations between 2005 and 2016 were included. The seroprevalence of
      the HBV surface antigen (HBsAg) and the levels of the antibody against the HBV
      surface antigen (anti-HBs) in each year group and sex were calculated. The levels
      of the antibody against the HBV core antigen were examined only for 2012 and
      2016. The APC model was used to analyze the HBV carrier rates. Results: The
      chronic HBV infection (HBsAg positivity) rate decreased from 9.7% in university
      students born before June 1974 to <1.0% in students born after 1992. The
      prevalence of anti-HBs positivity declined, particularly between the 1984-1988
      cohort (78.2%-53.2%) and the 1990-1994 cohort (60.6%-44.4%). Our APC model
      revealed that the chronic HBV carrier rate among the student population was
      affected significantly by age, period, and cohort (P < 0.001). Conclusions: HBV
      vaccination is one of the most effective strategies for preventing HBV infection.
      However, for complete eradication of HBV infection, the development of strategies
      that detect vaccination failure more effectively than current strategies do and
      early implementation of appropriate treatments are both necessary.

PMID- 29472995
TI  - Postnatal depression is associated with detrimental life-long and multi
      generational impacts on relationship quality.
AB  - Postnatal depression (PND) is known to be associated with a range of detrimental
      child and adolescent outcomes, resulting from its disruptive impact on mother
      child relationship quality. However, until now little has been known about the
      impact of PND on the longer-term relationships between mothers and their
      children, and any intergenerational effects this may have. Mother-child
      relationship quality is of interest from an evolutionary perspective as it plays
      a role in the accrual of offspring embodied capital, thus affecting offspring
      quality and offspring's capacity to subsequently invest in their own children.
      Relationships with offspring also mediate grandparent-grandchild relations; if
      PND negatively affects long-term mother-offspring relationship quality, it is
      also likely to negatively affect grandmaternal investment via reduced grandmother
      grandchild relationship quality. Here, we use responses to a retrospective
      questionnaire study of postmenopausal women, largely from the UK and US, to
      assess the impact of PND occurring in generation 1 on mother-child relationship
      quality across the life course of the child (generation 2) with whom it was
      associated, and also on the relationship quality with grandchildren (generation
      3) from that child. Average mother-child relationship quality was lower when the
      child's birth was associated with PND. Multi-level regression modelling found
      that mother-child relationship quality decreased as PND symptom severity
      increased after controlling for individual effects and a variety of other factors
      known to influence relationship quality (individual mothers n = 296, mother-child
      dyads n = 646). Additionally, intergenerational relationships appear to be
      affected, with PND negatively associated with grandmother-grandchild relations
      (individual grandmothers n = 125, relations with grandchildren from n = 197
      grandmother-parent dyads). That PND has long-term detrimental consequences for
      mother-child relationships, well beyond adolescence, highlights the need for
      investment in strategies to prevent PND and its cascade of negative
      multigenerational effects.

PMID- 29472996
TI  - Metagenomic analysis of orange colored protrusions from the muscle of Queen Conch
      Lobatus gigas (Linnaeus, 1758).
AB  - The endangered marine gastropod, Lobatus gigas, is an important fishery resource
      in the Caribbean region. Microbiological and parasitological research of this
      species have been poorly addressed despite its role in ecological fitness,
      conservation status and prevention of potential pathogenic infections. This study
      identified taxonomic groups associated with orange colored protrusions in the
      muscle of queen conchs using histological analysis, 454 pyrosequencing, and a
      combination of PCR amplification and automated Sanger sequencing. The molecular
      approaches indicate that the etiological agent of the muscle protrusions is a
      parasite belonging to the subclass Digenea. Additionally, the scope of the
      molecular technique allowed the detection of bacterial and fungi clades in the
      assignment analysis. This is the first evidence of a digenean infection in the
      muscle of this valuable Caribbean resource.

PMID- 29472997
TI  - A new Python library to analyse skeleton images confirms malaria parasite
      remodelling of the red blood cell membrane skeleton.
AB  - We present Skan (Skeleton analysis), a Python library for the analysis of the
      skeleton structures of objects. It was inspired by the "analyse skeletons" plugin
      for the Fiji image analysis software, but its extensive Application Programming
      Interface (API) allows users to examine and manipulate any intermediate data
      structures produced during the analysis. Further, its use of common Python data
      structures such as SciPy sparse matrices and pandas data frames opens the results
      to analysis within the extensive ecosystem of scientific libraries available in
      Python. We demonstrate the validity of Skan's measurements by comparing its
      output to the established Analyze Skeletons Fiji plugin, and, with a new scanning
      electron microscopy (SEM)-based method, we confirm that the malaria parasite
      Plasmodium falciparum remodels the host red blood cell cytoskeleton, increasing
      the average distance between spectrin-actin junctions.

PMID- 29472998
TI  - Vector competence of selected North American Anopheles and Culex mosquitoes for
      Zika virus.
AB  - Zika virus (ZIKV) is a vector-borne flavivirus that has caused recent outbreaks
      associated with serious disease in infants and newborns in the Americas. Aedes
      mosquitoes are the primary vectors for ZIKV, but little is known about the
      diversity of mosquitoes that can transmit ZIKV in North America. We chose three
      abundant North American mosquito species (Anopheles freeborni, Anopheles
      quadrimaculatus, and Culex tarsalis) and one known vector species (Aedes
      aegypti), fed them blood meals supplemented with a recent outbreak ZIKV strain,
      and tested bodies, legs, and saliva for infectious ZIKV. ZIKV was able to infect,
      disseminate, and be transmitted by Aedes aegypti. However, Anopheles freeborni,
      Anopheles quadrimaculatus, and Culex tarsalis were unable to be infected. We
      conclude that these species are unlikely to be involved in ZIKV transmission in
      North America. However, we should continue to examine the ability for other
      mosquito species to potentially act as ZIKV vectors in North America.

PMID- 29472999
TI  - Ontogeny of long-range vocalizations in a Neotropical fossorial rodent: the
      Anillaco Tuco-Tuco (Ctenomys sp.).
AB  - Tuco-tucos (Ctenomys spp.) are subterranean rodents that produce territorial,
      high intensity long-range vocalizations (LRVs) of broadband and low frequency
      that are essential for long-distance communication between individuals in
      different tunnel systems. Despite their importance, the development of LRVs
      remains poorly understood. In adult Anillaco Tuco-Tucos (Ctenomys sp.) the LRV is
      composed by two types of syllables (series and individual notes) that are
      repeated a variable number of times. We studied the development of the LRVs in
      eight juveniles of the Anillaco Tuco-Tuco ranging from 14-28 to 104-118 days
      after birth. We (1) tested whether the syllables followed any of three
      alternative developmental modes (retention of juvenile vocalizations,
      modification of juvenile precursors or de novo appearance in adults), (2)
      evaluated the development of structural and acoustic features of syllables, and
      (3) tested the prediction that juveniles should produce a greater proportion of
      atypical series in precursors of the LRV than adults, due to lack maturation
      and/or precise coupling of neuromuscular and anatomical structures. The LRV of
      the Anillaco Tuco-Tuco exhibited a mixed developmental mode: while series
      developed from juvenile precursors whose acoustic features gradually approached
      those of adults, individual notes appeared later in the ontogeny and de novo with
      acoustic features indistinguishable from those of adults. The number of series
      per vocalization increased through development and varied from one to 25 in
      juvenile males and from one to six in juvenile females. The structure of the most
      common series type (triad) did not exhibit ontogenetic changes and was present as
      such at the onset of the emission of vocalizations. On the contrary, acoustic
      features of juvenile triad notes changed with age in both sexes (duration 90%
      increased through development, while bandwidth 90% and peak frequency decreased).
      Furthermore, juveniles emitted a higher proportion of atypical series than adults
      (7.4% vs. 0.3%), as expected in the development of any complex behavior that
      requires practice to be mastered. The maturation of the LRV occurred well before
      the sexual maturation, presumably due to the protracted time needed to acquire or
      build a burrow system long before mating is possible. We propose that protracted
      vocal development is another component in the slow developmental strategy of
      Ctenomys and subterranean rodents in general.

PMID- 29473000
TI  - Morphometric analysis of a triple negative breast cancer cell line in hydrogel
      and monolayer culture environments.
AB  - Triple negative breast cancer (TNBC) is a belligerent carcinoma that is
      unresponsive to targeted receptor therapies. Development of new treatment
      strategies would benefit from an expanded repertoire of in vitro cell culture
      systems, such as those that support tridimensional growth in the presence of
      hydrogel scaffolds. To this end, we established protocols for maintenance of the
      TNBC cell line HCC70 in monolayer culture and in a commercially available
      basement membrane matrix hydrogel. We evaluated the general morphology of cells
      grown in both conditions with light microscopy, and examined their subcellular
      organization using transmission electron microscopy (TEM). Phase contrast and
      confocal microscopy showed the prevalence of irregularly shaped flattened cells
      in monolayer cultures, while cells maintained in hydrogel organized into multi
      layered spheroids. A quantitative ultrastructural analysis comparing cells from
      the two culture conditions revealed that cells that formed spheroids comprised a
      greater number of mitochondria, autophagic vacuoles and intercellular junctions
      than their monolayer counterparts, within the equivalent area of sampled tissue.
      These observations suggest that triple negative breast cancer cells in culture
      can alter their organelle content, as well as their morphology, in response to
      their microenvironment. Methods presented here may be useful for those who intend
      to image cell cultures with TEM, and for investigators who seek to implement
      diverse in vitro models in the search for therapeutic molecular targets for TNBC.

PMID- 29473001
TI  - Body mass index influences the plasma glucose concentration during iatrogenic
      hypoglycemia in people with type 2 diabetes mellitus: a cross-sectional study.
AB  - Background: Hypoglycemia occurs in an appreciable number of individuals with type
      2 diabetes mellitus (T2DM) who are receiving glycemic therapy. Iatrogenic
      hypoglycemia induces not only complications but also a substantial medical
      expense. Intervention for relevant risk factors may help avert severe
      hypoglycemia and enhance quality of life in at-risk individuals. This study
      investigates the relationship between body mass index (BMI) and plasma glucose
      concentration during iatrogenic hypoglycemia in people with T2DM. Methods:
      Enrollment criteria were people above 20 years of age, with existing diagnosis of
      T2DM, a documented plasma glucose level <=70 mg/dL, and acute cognitive
      impairment requiring hospitalization. Participants were classified into two
      groups according to their BMI. Specifically, lower BMI subgroup denotes
      individuals whose BMI fall within lower half of the study population, and vice
      versa. Plasma glucose concentration, length of hospital stay, and serum
      electrolyte level at hospitalization were compared between these BMI subgroups.
      Moreover, multivariate regression analysis was performed to identify covariates
      associated with plasma glucose level during iatrogenic hypoglycemia. Results:
      This study enrolled 107 participants for whom 54 were assigned to a higher BMI
      subgroup and the remainder to a lower BMI subgroup. People with lower BMI
      harbored substantially reduced plasma glucose concentration during iatrogenic
      hypoglycemia compared to those with higher BMI (30.1 +/- 9.6 mg/dL vs. 38.4 +/-
      12.3 mg/dL, P < 0.001). Nonetheless, the length of stay (6.2 +/- 4.6 days vs. 5.7
      +/- 4.0 days, P = 0.77) and serum potassium level (3.7 +/- 0.9 meq/L vs. 3.9 +/-
      0.8 meq/L, P = 0.14) were comparable between subgroups. Multivariate regression
      analysis identified BMI as a determinant of plasma glucose concentration in
      diabetic individuals with iatrogenic hypoglycemia (beta coefficient: 0.72, P =
      0.008). Discussion: In individuals with T2DM who experience severe iatrogenic
      hypoglycemia, BMI influences the plasma glucose level at hospitalization. People
      with lower BMI harbored appreciably reduced plasma glucose concentration relative
      to their higher BMI counterparts. In lower weight people, therefore, appropriate
      dosing of antidiabetic medications, frequent self-monitoring of blood glucose
      level and adequate nutritional support may help avert more severe hypoglycemia.
      Overall, BMI potentially influences the severity of iatrogenic hypoglycemia in
      people with T2DM.

PMID- 29473003
TI  - Optimization of antioxidative peptides from mackerel (Pneumatophorus japonicus)
      viscera.
AB  - Mackerel (Pneumatophorus japonicus) viscera contain large amount of protein. We
      used five proteases to hydrolyze the viscera, and the hydrolysate treated by
      neutrase exhibited the highest nitrogen recovery (NR). Then we optimized the
      preparation conditions for mackerel viscera hydrolysate (MVH) by response surface
      methodology and investigated the antioxidant activity of MVH. The optimal
      conditions were as follows: enzyme concentration of 1,762.87 U/g, pH of 6.76,
      temperature of 43.75  degrees C, extraction time of 6.0 h and water/material
      ratio of 20.37 (v/w), and the maximum NR was 37.84%. Furthermore, the molecular
      weight distribution of MVH was almost below 3,000 Da determined by TSK G2000 SWXL
      gel filtration chromatography, and the MVH exhibited good antioxidant activities
      in various in vitro assays, including DPPH radical, hydroxyl radical and
      superoxide anion scavenging activities, reducing power and similar effectivelness
      as butylated hydroxytoluene and Vitamin E to inhibit lipid peroxidation. The
      results suggested that MVH could be used as a potential source of antioxidant
      peptide in food industries.

PMID- 29473002
TI  - Genomic analysis of morphometric traits in bighorn sheep using the Ovine
      Infinium(r) HD SNP BeadChip.
AB  - Elucidating the genetic basis of fitness-related traits is a major goal of
      molecular ecology. Traits subject to sexual selection are particularly
      interesting, as non-random mate choice should deplete genetic variation and
      thereby their evolutionary benefits. We examined the genetic basis of three
      sexually selected morphometric traits in bighorn sheep (Ovis canadensis): horn
      length, horn base circumference, and body mass. These traits are of specific
      concern in bighorn sheep as artificial selection through trophy hunting opposes
      sexual selection. Specifically, horn size determines trophy status and, in most
      North American jurisdictions, if an individual can be legally harvested. Using
      between 7,994-9,552 phenotypic measures from the long-term individual-based study
      at Ram Mountain (Alberta, Canada), we first showed that all three traits are
      heritable (h2 = 0.15-0.23). We then conducted a genome-wide association study
      (GWAS) utilizing a set of 3,777 SNPs typed in 76 individuals using the Ovine
      Infinium(r) HD SNP BeadChip. We found suggestive association for body mass at a
      single locus (OAR9_91647990). The absence of strong associations with SNPs
      suggests that the traits are likely polygenic. These results represent a step
      forward for characterizing the genetic architecture of fitness related traits in
      sexually dimorphic ungulates.

PMID- 29473004
TI  - Catchment land use predicts benthic vegetation in small estuaries.
AB  - Many estuaries are becoming increasingly eutrophic from human activities within
      their catchments. Nutrient loads often are used to assess risk of eutrophication
      to estuaries, but such data are expensive and time consuming to obtain. We
      compared the percent of fertilized land within a catchment, dissolved inorganic
      nitrogen loads, catchment to estuary area ratio and flushing time as predictors
      of the proportion of macroalgae to total vegetation within 14 estuaries in south
      eastern Australia. The percent of fertilized land within the catchment was the
      best predictor of the proportion of macroalgae within the estuaries studied.
      There was a transition to a dominance of macroalgae once the proportion of
      fertilized land in the catchment exceeded 24%, highlighting the sensitivity of
      estuaries to catchment land use.

PMID- 29473005
TI  - Identification and expression profile analysis of the sucrose phosphate synthase
      gene family in Litchi chinensis Sonn.
AB  - Sucrose phosphate synthase (SPS, EC 2.4.1.14) is a key enzyme that regulates
      sucrose biosynthesis in plants. SPS is encoded by different gene families which
      display differential expression patterns and functional divergence. Genome-wide
      identification and expression analyses of SPS gene families have been performed
      in Arabidopsis, rice, and sugarcane, but a comprehensive analysis of the SPS gene
      family in Litchi chinensis Sonn. has not yet been reported. In the current study,
      four SPS gene (LcSPS1, LcSPS2, LcSPS3, and LcSPS4) were isolated from litchi. The
      genomic organization analysis indicated the four litchi SPS genes have very
      similar exon-intron structures. Phylogenetic tree showed LcSPS1-4 were grouped
      into different SPS families (LcSPS1 and LcSPS2 in A family, LcSPS3 in B family,
      and LcSPS4 in C family). LcSPS1 and LcSPS4 were strongly expressed in the
      flowers, while LcSPS3 most expressed in mature leaves. RT-qPCR results showed
      that LcSPS genes expressed differentially during aril development between
      cultivars with different hexose/sucrose ratios. A higher level of expression of
      LcSPS genes was detected in Wuheli, which accumulates higher sucrose in the aril
      at mature. The tissue- and developmental stage-specific expression of LcSPS1-4
      genes uncovered in this study increase our understanding of the important roles
      played by these genes in litchi fruits.

PMID- 29473006
TI  - Benthic grazing in a eutrophic river: cascading effects of zoobenthivorous fish
      mask direct effects of herbivorous fish.
AB  - Benthic grazing strongly controls periphyton biomass. The question therefore
      arises whether benthic grazing could be used as a tool to reduce excessive growth
      of periphyton in nutrient-enriched rivers. Although benthic invertebrate grazers
      reduce the growth of periphyton, this is highly context dependent. Here we
      assessed whether the only obligate herbivorous fish in European rivers, the
      common nase (Chondrostoma nasus L.), is able to reduce periphyton biomass in a
      eutrophic river. We conducted three consecutive in situ experiments at low,
      intermediate and high densities of nase in the river using standard tiles on the
      river bottom naturally covered with periphyton that were accessible to fish and
      tiles that excluded fish foraging with electric exclosures. The biomass of
      benthic invertebrate grazers was very low relative to nase. We hypothesised that
      nase would reduce periphyton biomass on accessible tiles and therefore expected
      higher periphyton biomass on the exclosure tiles, at least at intermediate and
      high densities of nase in the river. Contrary to our expectation, the impact of
      fish grazing was low even at high fish density, as judged by the significantly
      lower chlorophyll a concentration on exclosure tiles even though the ash-free dry
      mass on accessible and exclosure tiles did not differ. The lower chlorophyll a
      concentrations on exclosure tiles might be explained by a higher biomass of
      invertebrate grazers on the exclosure tiles, which would indicate that the effect
      of invertebrate grazers was stronger than that of herbivorous fish grazers. The
      high biomass of invertebrate grazers on exclosure tiles likely arose from the
      exclusion of zoobenthivorous fish, which occur in the river at high densities.
      The results of our small-scale experiments suggested that cascading top-down
      effects of zoobenthivorous fish have a higher impact on periphyton biomass than
      direct effects of herbivorous nase.

PMID- 29473007
TI  - High-resolution modeling of thermal thresholds and environmental influences on
      coral bleaching for local and regional reef management.
AB  - Coral reefs are one of the world's most threatened ecosystems, with global and
      local stressors contributing to their decline. Excessive sea-surface temperatures
      (SSTs) can cause coral bleaching, resulting in coral death and decreases in coral
      cover. A SST threshold of 1  degrees C over the climatological maximum is widely
      used to predict coral bleaching. In this study, we refined thermal indices
      predicting coral bleaching at high-spatial resolution (1 km) by statistically
      optimizing thermal thresholds, as well as considering other environmental
      influences on bleaching such as ultraviolet (UV) radiation, water turbidity, and
      cooling effects. We used a coral bleaching dataset derived from the web-based
      monitoring system Sango Map Project, at scales appropriate for the local and
      regional conservation of Japanese coral reefs. We recorded coral bleaching events
      in the years 2004-2016 in Japan. We revealed the influence of multiple factors on
      the ability to predict coral bleaching, including selection of thermal indices,
      statistical optimization of thermal thresholds, quantification of multiple
      environmental influences, and use of multiple modeling methods (generalized
      linear models and random forests). After optimization, differences in predictive
      ability among thermal indices were negligible. Thermal index, UV radiation, water
      turbidity, and cooling effects were important predictors of the occurrence of
      coral bleaching. Predictions based on the best model revealed that coral reefs in
      Japan have experienced recent and widespread bleaching. A practical method to
      reduce bleaching frequency by screening UV radiation was also demonstrated in
      this paper.

PMID- 29473008
TI  - Codominant grasses differ in gene expression under experimental climate extremes
      in native tallgrass prairie.
AB  - Extremes in climate, such as heat waves and drought, are expected to become more
      frequent and intense with forecasted climate change. Plant species will almost
      certainly differ in their responses to these stressors. We experimentally imposed
      a heat wave and drought in the tallgrass prairie ecosystem near Manhattan,
      Kansas, USA to assess transcriptional responses of two ecologically important C4
      grass species, Andropogon gerardii and Sorghastrum nutans. Based on previous
      research, we expected that S. nutans would regulate more genes, particularly
      those related to stress response, under high heat and drought. Across all
      treatments, S. nutans showed greater expression of negative regulatory and
      catabolism genes while A. gerardii upregulated cellular and protein metabolism.
      As predicted, S. nutans showed greater sensitivity to water stress, particularly
      with downregulation of non-coding RNAs and upregulation of water stress and
      catabolism genes. A. gerardii was less sensitive to drought, although A. gerardii
      tended to respond with upregulation in response to drought versus S. nutans which
      downregulated more genes under drier conditions. Surprisingly, A. gerardii only
      showed minimal gene expression response to increased temperature, while S. nutans
      showed no response. Gene functional annotation suggested that these two species
      may respond to stress via different mechanisms. Specifically, A. gerardii tends
      to maintain molecular function while S. nutans prioritizes avoidance. Sorghastrum
      nutans may strategize abscisic acid response and catabolism to respond rapidly to
      stress. These results have important implications for success of these two
      important grass species under a more variable and extreme climate forecast for
      the future.

PMID- 29473009
TI  - COREMIC: a web-tool to search for a niche associated CORE MICrobiome.
AB  - Microbial diversity on earth is extraordinary, and soils alone harbor thousands
      of species per gram of soil. Understanding how this diversity is sorted and
      selected into habitat niches is a major focus of ecology and biotechnology, but
      remains only vaguely understood. A systems-biology approach was used to mine
      information from databases to show how it can be used to answer questions related
      to the core microbiome of habitat-microbe relationships. By making use of the
      burgeoning growth of information from databases, our tool "COREMIC" meets a great
      need in the search for understanding niche partitioning and habitat-function
      relationships. The work is unique, furthermore, because it provides a user
      friendly statistically robust web-tool (http://coremic2.appspot.com or
      http://core-mic.com), developed using Google App Engine, to help in the process
      of database mining to identify the "core microbiome" associated with a given
      habitat. A case study is presented using data from 31 switchgrass rhizosphere
      community habitats across a diverse set of soil and sampling environments. The
      methodology utilizes an outgroup of 28 non-switchgrass (other grasses and forbs)
      to identify a core switchgrass microbiome. Even across a diverse set of soils
      (five environments), and conservative statistical criteria (presence in more than
      90% samples and FDR q-val <0.05% for Fisher's exact test) a core set of bacteria
      associated with switchgrass was observed. These included, among others, closely
      related taxa from Lysobacter spp., Mesorhizobium spp, and Chitinophagaceae. These
      bacteria have been shown to have functions related to the production of bacterial
      and fungal antibiotics and plant growth promotion. COREMIC can be used as a
      hypothesis generating or confirmatory tool that shows great potential for
      identifying taxa that may be important to the functioning of a habitat (e.g. host
      plant). The case study, in conclusion, shows that COREMIC can identify key
      habitat-specific microbes across diverse samples, using currently available
      databases and a unique freely available software.

PMID- 29473010
TI  - Expanded Access Programs: Ethical and Practical Considerations for
      Biopharmaceutical Sponsors.
AB  - Expanded access is a regulatory mechanism by which an investigational drug can be
      made available outside of a clinical trial to treat patients with serious or life
      threatening conditions for which there are no satisfactory treatment options. An
      expanded access program (EAP) is the formal plan under which preapproval access
      to an investigational drug can be provided to a group of patients. Although an
      EAP is a regulated program, the decision to authorize an EAP is the
      responsibility of the biopharmaceutical sponsor. Because of the significant
      impact an EAP can have on current patients, drug development, and future
      patients, we propose that a sponsor's decision must be based not only on
      regulatory criteria but also on ethical and practical considerations regarding
      implementation of an EAP. Such an approach will help ensure that decisions and
      plans uphold ethical precepts such as fairness, promoting good, and minimizing
      risk of harm.

PMID- 29473011
TI  - Use of 3D Navigation in Subaxial Cervical Spine Lateral Mass Screw Insertion.
AB  - Objective  Cervical spine can be stabilized by different techniques. One of the
      common techniques used is the lateral mass screws (LMSs), which can be inserted
      either by freehand techniques or three-dimensional (3D) navigation system. The
      purpose of this study is to evaluate the difference between the 3D navigation
      system and the freehand technique for cervical spine LMS placement in terms of
      complications. Including intraoperative complications (vertebral artery injury
      [VAI], nerve root injury [NRI], spinal cord injury [SCI], lateral mass fracture
      [LMF]) and postoperative complications (screw malposition, screw complications).
      Methods  Patients who had LMS fixation for their subaxial cervical spine from
      January 2014 to April 2015 at the Ottawa Hospital were included. A total of 284
      subaxial cervical LMS were inserted in 40 consecutive patients. Surgical
      indications were cervical myelopathy and fractures. The screws' size was 3.5 mm
      in diameter and 8 to 16 mm in length. During the insertion of the subaxial
      cervical LMS, the 3D navigation system was used for 20 patients, and the freehand
      technique was used for the remaining 20 patients. We reviewed the charts, X-rays,
      computed tomography (CT) scans, and follow-up notes for all the patients pre- and
      postoperatively. Results  Postoperative assessment showed that the incidence of
      VAI, SCI, and NRI were the same between the two groups. The CT scan analysis
      showed that the screw breakage, screw pull-outs, and screw loosening were the
      same between the two groups. LMF was less in the 3D navigation group but
      statistically insignificant. Screw malposition was less in the 3D navigation
      group compared with the freehand group and was statistically significant. The
      hospital stay, operative time, and blood loss were statistically insignificant
      between the two groups. Conclusions  The use of CT-based navigation in LMS
      insertion decreased the rate of screw malpositions as compared with the freehand
      technique. Further investigations and trials will determine the effect of
      malpositions on the c-spine biomechanics. The use of navigation in LMS insertion
      did not show a significant difference in VAI, LMF, SCI, or NRI as compared with
      the freehand technique.

PMID- 29473012
TI  - Nuss Procedure for a Patient with Negative Haller Index.
AB  - Introduction  Minimally invasive repair for pectus excavatum (MIRPE) is
      controversial in extremely severe cases of pectus excavatum (PE) and an open
      repair is usually favored. Our aim is to describe a case of a patient with an
      extremely severe PE that underwent a minimally invasive approach. Case report  An
      8-year-old girl with severe sternum depression was assessed. She had a history of
      exercise intolerance, nocturnal dyspnea, fatigue, and shortness of breath. Chest
      computed tomography showed that sternum depression was posterior to the anterior
      vertebral column; therefore, Haller and correction index could not be measured.
      Spirometry indicated an obstructive ventilation pattern (forced expiratory volume
      in 1 second = 74.4%), and echocardiogram revealed a dilated inferior vena cava,
      mitral valve prolapse with normal ventricular function. After multidisciplinary
      committee evaluation, a MIRPE approach was performed. All symptoms had
      disappeared at the 3-month postoperative follow-up; the desired sternum shape was
      achieved and normalization of cardiopulmonary function was observed. The Nuss
      bars were removed after a 2-year period. After 18-month follow-up, the patient
      can carry out normal exercise and is content with the cosmetic result. Conclusion
      Nuss procedure is feasible in our 8-year-old patient. In this case, both the
      Haller and correction index were not useful to assess the severity of PE.
      Therefore, under these circumstances, other radiologic parameters have to be
      taken into consideration for patient evaluation.

PMID- 29473013
TI  - High-Risk Repair of Traumatic Mitral Valve Rupture in the Setting of Polytrauma.
AB  - Background  The rare complication of mitral valve rupture from blunt trauma is
      certainly not at the top of the differential of shock. Case Description  We
      report the case of a 56-year-old woman who sustained numerous injuries after a 30
      m fall with cardiogenic shock secondary to mitral valve rupture causing severe
      mitral valve regurgitation. Management included successful primary leaflet
      repair, annuloplasty, and single vessel coronary artery bypass. Conclusion 
      Valvular repair in the setting of polytrauma is a complex decision that requires
      careful balance of risks and benefits relative to patient stability.

PMID- 29473014
TI  - Angiosarcoma of the Left Atrium: A Case Report.
AB  - Background  Primary cardiac tumors are rare, and many diagnosed tumors are benign
      with an incidence of 0.001% to 0.03%. The primary angiosarcoma is one of the
      malignant entities. Discussion  We discuss a case report of a 76-year-old male
      who underwent a preoperative diagnosis for an upcoming shoulder operation when
      his cardiologist diagnosed a large cardiac tumor. The patient was referred to our
      department where he received further diagnostics. The transesophageal
      echocardiography and the cardiac-magnetic resonance imaging showed a massive
      tumor with a dimension of 8.6 * 5.6 cm with no signs of malignity. Method  The
      operation was performed by standard median sternotomy. The tumor was adherent to
      the septum and the left atrium, and we were able to remove the specimen in toto.
      Pathological examinations showed an angiosarcoma with neovascularization and core
      expression of ERG+ and cytoplasmic expression of CD31+/CD34+, due to the size of
      the mass. The resection of primary cardiac tumors is mostly the therapy of
      choice, but in this case concerning an angiosarcoma the prognosis is poor,
      considering that the angiosarcoma responds very badly to chemotherapy and
      radiotherapy.

PMID- 29473015
TI  - Molecular analysis of integrons and antimicrobial resistance profile in Shigella
      spp. isolated from acute pediatric diarrhea patients.
AB  - Introduction:Shigella spp. is a growing global health concern due to increasing
      multiple drug resistance, commonly resulting in therapeutic failure. Integrons
      are gene expression systems run by integrase genes. The aims of this study were
      detection of class I, II and III integrons and assessment of antimicrobial
      resistance in Shigella spp. isolated from acute pediatric diarrhea patients.
      Materials and methods: From January to December 2015, 16 Shigella spp. were
      isolated from 310 non-duplicative diarrheal stool samples in Children's Medical
      Center, Tehran, Iran. The isolates were analyzed for their antibiotic
      susceptibility using CLSI guidelines M100-S14. Multiplex PCR was used for
      amplification of I, II and III integron-associated integrase (intl) genes.
      Results: Of 310 stool samples, 16 (5.2%) were positive for Shigella spp., in 7 of
      them S. sonnei and in 9 of them S. flexneri were identified. Results of the
      antimicrobial susceptibility test showed that 6.2%, 50%, 31.2%, 6.2%, 81.2%,
      56.2% and 31.2% of the isolates were resistant to gentamicin, chloramphenicol,
      nalidixic acid, ciprofloxacin, tetracycline, ampicillin and trimethoprim
      sulfamethoxazole, respectively. Multiplex PCR results revealed that 6.2% (1/16),
      31.2% (5/16), 50% (8/16) of Shigella isolates carried intlI, intlII and both
      intlI/intllI genes. No class 3 integrons were detected. Discussion: In this
      study, multidrug resistance was seen in Shigella isolates similar to that in
      isolates from other geographical areas. This is possible due to inappropriate use
      of antimicrobials. Furthermore, prevalence of multidrug resistance was
      significantly linked to the presence of integrin genes. Conclusion: A class 2
      integron plays a role in presence of multidrug resistance in Shigella spp. It is
      vital to prevent the spread of antibiotic resistance through continuous
      monitoring.

PMID- 29473016
TI  - Editorial: New Approaches to Radiation-Therapeutic Agent Cancer Care for Women.

PMID- 29473017
TI  - Roadmap to Wellness: Exploring Live Customized Music at the Bedside for
      Hospitalized Children.
AB  - Background: Randomized trials on clinical outcomes of music are conflicting, with
      few performed in the postoperative pediatric population. We aimed to determine if
      there was a benefit of a live, customized bedside music delivery program
      (MyMusicRx(r)) for children hospitalized after pediatric surgery. We present our
      perspective on the utility of music medicine, review others' work in this area,
      and discuss future directions. Methods: All admitted postsurgical patients aged
      between 5 and 18 years were considered. One live, customized music session was
      delivered by a MyMusicRx(r) music specialist to intervention participants, and
      compared with matched controls who did not receive music intervention. Pain,
      cumulative analgesia dosage, and vital signs within 12 h after unit arrival were
      compared between groups. Results: Thirty-two participants (16 intervention, 16
      controls; 8:8 females:males per group) were enrolled. No differences in age,
      surgery length, or duration of music intervention were found between groups. No
      differences in pain scores (p = 0.73), heart rate (p = 0.82), respirations (p =
      84), narcotic (p = 0.92) or non-narcotic medication usage (p = 0.88, 0.86, 0.95;
      ibuprofen, acetaminophen, and ketorolac, respectively), or time to first narcotic
      dose (p = 0.64) were found. Conclusion: A single music intervention in the acute
      postoperative period did not appear to be adequate to augment traditional methods
      of pain and hemodynamic control. Prior studies have similar outcome measures but
      conflicting results. We did not evaluate psychological well-being, patient
      engagement, or family perception in this pilot study. Future directions include
      developing and validating a tool that explores the observable impact of music
      medicine on children's emotions and behaviors.

PMID- 29473018
TI  - A Global Analysis of Kinase Function in Candida albicans Hyphal Morphogenesis
      Reveals a Role for the Endocytosis Regulator Akl1.
AB  - The human pathogenic fungus Candida albicans can switch between yeast and hyphal
      morphologies as a function of environmental conditions and cellular physiology.
      The yeast-to-hyphae morphogenetic switch is activated by well-established, kinase
      based signal transduction pathways that are induced by extracellular stimuli. In
      order to identify possible inhibitory pathways of the yeast-to-hyphae transition,
      we interrogated a collection of C. albicans protein kinases and phosphatases
      ectopically expressed under the regulation of the TETon promoter. Proportionately
      more phosphatases than kinases were identified that inhibited hyphal
      morphogenesis, consistent with the known role of protein phosphorylation in
      hyphal induction. Among the kinases, we identified AKL1 as a gene that
      significantly suppressed hyphal morphogenesis in serum. Akl1 specifically
      affected hyphal elongation rather than initiation: overexpression of AKL1
      repressed hyphal growth, and deletion of AKL1 resulted in acceleration of the
      rate of hyphal elongation. Akl1 suppressed fluid-phase endocytosis, probably via
      Pan1, a putative clathrin-mediated endocytosis scaffolding protein. In the
      absence of Akl1, the Pan1 patches were delocalized from the sub-apical region,
      and fluid-phase endocytosis was intensified. These results underscore the
      requirement of an active endocytic pathway for hyphal morphogenesis. Furthermore,
      these results suggest that under standard conditions, endocytosis is rate
      limiting for hyphal elongation.

PMID- 29473019
TI  - Utilization of Different Omic Approaches to Unravel Stress Response Mechanisms in
      the Parasite Entamoeba histolytica.
AB  - During its life cycle, the unicellular parasite Entamoeba histolytica is
      challenged by a wide variety of environmental stresses, such as fluctuation in
      glucose concentration, changes in gut microbiota composition, and the release of
      oxidative and nitrosative species from neutrophils and macrophages. The best mode
      of survival for this parasite is to continuously adapt itself to the dynamic
      environment of the host. Our ability to study the stress-induced responses and
      adaptive mechanisms of this parasite has been transformed through the development
      of genomics, proteomics or metabolomics (omics sciences). These studies provide
      insights into different facets of the parasite's behavior in the host. However,
      there is a dire need for multi-omics data integration to better understand its
      pathogenic nature, ultimately paving the way to identify new chemotherapeutic
      targets against amebiasis. This review provides an integration of the most
      relevant omics information on the mechanisms that are used by E. histolytica to
      resist environmental stresses.

PMID- 29473020
TI  - Functional Analysis of the Chaperone-Usher Fimbrial Gene Clusters of Salmonella
      enterica serovar Typhi.
AB  - The human-specific pathogen Salmonella enterica serovar Typhi causes typhoid, a
      major public health issue in developing countries. Several aspects of its
      pathogenesis are still poorly understood. S. Typhi possesses 14 fimbrial gene
      clusters including 12 chaperone-usher fimbriae (stg, sth, bcf, fim, saf, sef,
      sta, stb, stc, std, ste, and tcf). These fimbriae are weakly expressed in
      laboratory conditions and only a few are actually characterized. In this study,
      expression of all S. Typhi chaperone-usher fimbriae and their potential roles in
      pathogenesis such as interaction with host cells, motility, or biofilm formation
      were assessed. All S. Typhi fimbriae were better expressed in minimal broth. Each
      system was overexpressed and only the fimbrial gene clusters without pseudogenes
      demonstrated a putative major subunits of about 17 kDa on SDS-PAGE. Six of these
      (Fim, Saf, Sta, Stb, Std, and Tcf) also show extracellular structure by electron
      microscopy. The impact of fimbrial deletion in a wild-type strain or addition of
      each individual fimbrial system to an S. Typhi afimbrial strain were tested for
      interactions with host cells, biofilm formation and motility. Several fimbriae
      modified bacterial interactions with human cells (THP-1 and INT-407) and biofilm
      formation. However, only Fim fimbriae had a deleterious effect on motility when
      overexpressed. Overall, chaperone-usher fimbriae seem to be an important part of
      the balance between the different steps (motility, adhesion, host invasion and
      persistence) of S. Typhi pathogenesis.

PMID- 29473022
TI  - Intranasal Immunization with DnaK Protein Induces Protective Mucosal Immunity
      against Tuberculosis in CD4-Depleted Mice.
AB  - Mycobacterium tuberculosis (Mtb) remains a global health challenge due to the
      limited efficacy of the Mtb vaccine in current use, Bacillus Calmette-Guerin
      (BCG). To date, there is no available vaccine for immunocompromised individuals.
      Thus, there is an urgent need to develop a new vaccine candidate which can induce
      mucosal immunity in hosts with different immune statuses. DnaK (HSP70) has been
      shown to induce protective immunity against Mtb infection when administered by
      DNA vaccine; however, the protection is inferior to that induced by the BCG
      vaccine. In our study, we vaccinated C57BL/6J mice with DnaK protein alone.
      Subcutaneous or intranasal vaccination with DnaK generated IFNgamma-secreting
      CD4+ T cells in the spleen, but only intranasal vaccination generated IL-17
      releasing CD4+ T cells in the lungs, even when circulating CD4+ T cells were
      diminished. Furthermore, intranasal vaccination with DnaK generated tissue
      resident CD4+ T cells in the lungs. Vaccination with DnaK alone resulted in
      protective immunity comparable to BCG vaccination against tuberculosis in mice.
      Our results demonstrate that intranasal vaccination with DnaK can generate
      mucosal immunity in immunocompromised or immunocompetent mice and DnaK
      vaccination can generate protection against Mtb similar to BCG, underscoring its
      potential utility as an Mtb vaccine candidate in humans.

PMID- 29473021
TI  - Clostridioides difficile Biology: Sporulation, Germination, and Corresponding
      Therapies for C. difficile Infection.
AB  - Clostridioides difficile is a Gram-positive, spore-forming, toxin-producing
      anaerobe, and an important nosocomial pathogen. Due to the strictly anaerobic
      nature of the vegetative form, spores are the main morphotype of infection and
      transmission of the disease. Spore formation and their subsequent germination
      play critical roles in C. difficile infection (CDI) progress. Under suitable
      conditions, C. difficile spores will germinate and outgrow to produce the
      pathogenic vegetative form. During CDI, C. difficile produces toxins (TcdA and
      TcdB) that are required to initiate the disease. Meanwhile, it also produces
      spores that are responsible for the persistence and recurrence of C. difficile in
      patients. Recent studies have shed light on the regulatory mechanisms of C.
      difficile sporulation and germination. This review is to summarize recent
      advances on the regulation of sporulation/germination in C. difficile and the
      corresponding therapeutic strategies that are aimed at these important processes.

PMID- 29473023
TI  - Basic Characterization of Natural Transformation in a Highly Transformable
      Haemophilus parasuis Strain SC1401.
AB  - Haemophilus parasuis causes Glasser's disease and pneumonia, incurring serious
      economic losses in the porcine industry. In this study, natural competence was
      investigated in H. parasuis. We found competence genes in H. parasuis homologous
      to ones in Haemophilus influenzae and a high consensus battery of Sxy-dependent
      cyclic AMP (cAMP) receptor protein (CRP-S) regulons using bioinformatics. High
      rates of natural competence were found from the onset of stationary-phase growth
      condition to mid-stationary phase (OD600 from 0.29 to 1.735); this rapidly
      dropped off as cells reached mid-stationary phase (OD600 from 1.735 to 1.625). As
      a whole, bacteria cultured in liquid media were observed to have lower competence
      levels than those grown on solid media plates. We also revealed that natural
      transformation in this species is stable after 200 passages and is largely
      dependent on DNA concentration. Transformation competition experiments showed
      that heterogeneous DNA cannot outcompete intraspecific natural transformation,
      suggesting an endogenous uptake sequence or other molecular markers may be
      important in differentiating heterogeneous DNA. We performed qRT-PCR targeting
      multiple putative competence genes in an effort to compare bacteria pre-cultured
      in TSB++ vs. TSA++ and SC1401 vs. SH0165 to determine expression profiles of the
      homologs of competence-genes in H. influenzae. Taken together, this study is the
      first to investigate natural transformation in H. parasuis based on a highly
      naturally transformable strain SC1401.

PMID- 29473025
TI  - Dynamics and Control of Flagella Assembly in Salmonella typhimurium.
AB  - The food-borne pathogen Salmonella typhimurium is a common cause of infections
      and diseases in a wide range of hosts. One of the major virulence factors
      associated to the infection process is flagella, which helps the bacterium swim
      to its preferred site of infection inside the host, the M-cells (Microfold cells)
      lining the lumen of the small intestine. The expression of flagellar genes is
      controlled by an intricate regulatory network. In this work, we investigate two
      aspects of flagella regulation and assembly: (a) distribution of the number of
      flagella in an isogenic population of bacteria and (b) dynamics of gene
      expression post cell division. More precisely, in a population of bacteria, we
      note a normal distribution of number of flagella assembled per cell. How is this
      distribution controlled, and what are the key regulators in the network which
      help the cell achieve this? In the second question, we explore the role of
      protein secretion in dictating gene expression dynamics post cell-division (when
      the number of hook basal bodies on the cell surface is reduced by a factor of
      two). We develop a mathematical model and perform stochastic simulations to
      address these questions. Simulations of the model predict that two accessory
      regulators of flagella gene expression, FliZ and FliT, have significant roles in
      maintaining population level distribution of flagella. In addition, FliT and FlgM
      were predicted to control the level and temporal order of flagellar gene
      expression when the cell adapts to post cell division consequences. Further, the
      model predicts that, the FliZ and FliT dependent feedback loops function under
      certain thresholds, alterations in which can substantially affect kinetics of
      flagellar genes. Thus, based on our results we propose that, the proteins FlgM,
      FliZ, and FliT, thought to have accessory roles in regulation of flagella, likely
      play a critical role controlling gene expression during cell division, and
      frequency distribution of flagella.

PMID- 29473026
TI  - Mitigating Latent Threats Identified through an Embedded In Situ Simulation
      Program and Their Comparison to Patient Safety Incidents: A Retrospective Review.
AB  - Objective: To assess the impact of service improvements implemented because of
      latent threats (LTs) detected during in situ simulation. Design: Retrospective
      review from April 2008 to April 2015. Setting: Paediatric Intensive Care Unit in
      a specialist tertiary hospital. Intervention: Service improvements from LTs
      detection during in situ simulation. Action plans from patient safety incidents
      (PSIs). Main outcome measures: The quantity, category, and subsequent service
      improvements for LTs. The quantity, category, and subsequent action plans for
      PSIs. Similarities between PSIs and LTs before and after service improvements.
      Results: 201 Simulated inter-professional team training courses with 1,144 inter
      professional participants. 44 LTs were identified (1 LT per 4.6 courses).
      Incident severity varied: 18 (41%) with the potential to cause harm, 20 (46%)
      that would have caused minimal harm, and 6 (13%) that would have caused
      significant temporary harm. Category analysis revealed the majority of LTs were
      resources (36%) and education and training (27%). The remainder consisted of
      equipment (11%), organizational and strategic (7%), work and environment (7%),
      medication (7%), and systems and protocols (5%). 43 service improvements were
      developed: 24 (55%) resources/equipment; 9 (21%) educational; 6 (14%)
      organizational changes; 2 (5%) staff communications; and 2 (5%) guidelines. Four
      (9%) service improvements were adopted trust wide. 32 (73%) LTs did not recur
      after service improvements. 24 (1%) of 1,946 PSIs were similar to LTs: 7 resource
      incidents, 7 catastrophic blood loss, 4 hyperkalaemia arrests, 3 emergency buzzer
      failures, and 3 difficulties contacting staff. 34 LTs (77%) were never recorded
      as PSIs. Conclusion: An in situ simulation program can identify important LTs
      which traditional reporting systems miss. Subsequent improvements in workplace
      systems and resources can improve efficiency and remove error traps.

PMID- 29473024
TI  - Plasmodium vivax Biology: Insights Provided by Genomics, Transcriptomics and
      Proteomics.
AB  - During the last decade, the vast omics field has revolutionized biological
      research, especially the genomics, transcriptomics and proteomics branches, as
      technological tools become available to the field researcher and allow difficult
      question-driven studies to be addressed. Parasitology has greatly benefited from
      next generation sequencing (NGS) projects, which have resulted in a broadened
      comprehension of basic parasite molecular biology, ecology and epidemiology.
      Malariology is one example where application of this technology has greatly
      contributed to a better understanding of Plasmodium spp. biology and host
      parasite interactions. Among the several parasite species that cause human
      malaria, the neglected Plasmodium vivax presents great research challenges, as in
      vitro culturing is not yet feasible and functional assays are heavily limited.
      Therefore, there are gaps in our P. vivax biology knowledge that affect decisions
      for control policies aiming to eradicate vivax malaria in the near future. In
      this review, we provide a snapshot of key discoveries already achieved in P.
      vivax sequencing projects, focusing on developments, hurdles, and limitations
      currently faced by the research community, as well as perspectives on future
      vivax malaria research.

PMID- 29473027
TI  - Morphology and Function of the Lamb Ileum following Preterm Birth.
AB  - Background: For infants born moderately/late preterm (32-37 weeks of gestation),
      immaturity of the intestine has the potential to impact both short- and long-term
      gastrointestinal function. The aim of this study conducted in sheep was to
      compare the morphology and smooth muscle contractility of the ileum in term and
      late preterm lambs. Materials and methods: Lambs delivered preterm (132 days
      gestation; n = 7) or term (147 days gestation; n = 9) were milk-fed after birth
      and euthanased at 2 days of age. A segment of distal ileum was collected for
      analysis of the length and cellular composition of the villi and crypts, smooth
      muscle width and contractility, and mRNA expression of the cell markers Ki67,
      lysozyme, mucin 2, synaptophysin, chromogranin A, olfactomedin 4, axis inhibition
      protein 2, and leucine-rich repeat-containing G-protein coupled receptor 5
      (LGR5). Results: There was no difference in the proportion of inflammatory,
      proliferating, apoptotic, enterocyte, or goblet cells between groups, but preterm
      lambs exhibited a significant upregulation of the stem cell marker LGR5 (p =
      0.01). Absolute villus height (term: 1,032 +/- 147 um, preterm: 651 +/- 52 um; p
      < 0.0001) and crypt depth (term: 153 +/- 11 um, preterm: 133 +/- 17 um; p = 0.01)
      were significantly shorter in the preterm ileums, with a trend (p = 0.06) for a
      reduction in muscularis externa width. There was no difference between groups in
      the contractile response to acetylcholine, but peak contractility in response to
      bradykinin (p = 0.02) and angiotensin II (p = 0.03) was significantly greater in
      the preterm lambs. Conclusion: Findings demonstrate that the crypt-villus units
      are shorter in the ileum of late preterm offspring, but functionally mature with
      an equivalent cellular composition and normal contractile response to
      acetylcholine compared with term offspring. The exaggerated contractility to
      inflammatory mediators evident in the preterm ileum, however, may be of concern.

PMID- 29473028
TI  - Results of Onlay Preputial Flap Urethroplasty for the Single-Stage Repair of Mid-
      and Proximal Hypospadias.
AB  - Aims: To report current results of preputial flap onlay urethroplasty using the
      principle of the total preputial flap (TPF) for the one-stage repair of mid- and
      proximal hypospadias. Methods: This study was a retrospective chart review of
      patients in a prospectively kept database of all hypospadias operations performed
      at two institutions from January 1 2011 to August 2017. Inclusion criteria: all
      patients who underwent hypospadias repair using a preputial only flap
      urethroplasty based on the principle of the TPF. Demographic data, duration of
      follow-up, complications, and reoperations were recorded. A successful result was
      considered to be a straight penis, a glanular meatus, and absence of voiding
      symptoms. Whenever possible an uroflow was obtained during the follow-up visits.
      Results: Forty-nine children met the inclusion criteria. All patients had marked
      penile curvature. Three patients had chromosomal abnormalities. The mean age at
      the time of surgery was 22 months (11-110) and the mean duration of follow-up
      23.4 months (1-79). In 48 cases, the urethral plate could be preserved without
      dividing it. The penile curvature was corrected with chordectomy alone in 10
      patients, 38 required a dorsal plication of the tunica albuginea, and 1 required
      an additional ventral dermal graft. In 38 patients (77.5%), the initial operation
      was successful, and no further operations were needed. There were eight
      urethrocutaneous fistulas, three dehiscences of the glans approximation. One
      patient suffered a wound infection and partial loss of the flap. Conclusion: One
      stage repair of mid- and proximal hypospadias preserving the urethral plate and
      using a TPF for the urethroplasty and coverage of the ventral penis is successful
      in 77.5% of cases. Complications in the remaining patients were easily managed or
      did not require treatment. Compared to a planned two-stage approach, the
      technique described in this report resulted in significantly fewer procedures
      till complete resolution of the problem.

PMID- 29473030
TI  - Public Health Investment in Team Care: Increasing Access to Clinical Preventive
      Services in Los Angeles County.
AB  - As part of federal and local efforts to increase access to high quality, clinical
      preventive services (CPS) in underserved populations, the Los Angeles County
      Department of Public Health (DPH) partnered with six local health system and
      community organization partners to promote the use of team care for CPS delivery.
      Although these partners were at different stages of organizational capacity, post
      program review suggests that each organization advanced team care in their
      clinical or community environments, potentially affecting >250,000 client visits
      per year. Despite existing infrastructure and DPH's funding support of CPS
      integration, partner efforts faced several challenges. They included lack of
      sustainable funding for prevention services; limited access to community
      resources that support disease prevention; and difficulties in changing health
      care provider behavior. Although team care can serve as a catalyst or vehicle for
      delivering CPS, downstream sustainability of this model of practice requires
      further state and national policy changes that prioritize prevention. Public
      health is well positioned to facilitate these policy discussions and to assist
      health system and community organizations in strengthening CPS integration.

PMID- 29473029
TI  - Fluoxetine Administration in Juvenile Monkeys: Implications for Pharmacotherapy
      in Children.
AB  - Fluoxetine therapy has been approved for children with major depressive disorder
      and obsessive compulsive disorder for over 14 years and has expanded to other
      childhood behavior disorders. As use increases, more detail on fluoxetine effects
      during juvenile brain development can help maintain safe and effective use of
      this therapy. Here, a narrative review is provided of previously published
      findings from a large nonhuman primate project. Fluoxetine was administered to
      juvenile male rhesus monkeys for an extended period (2 years) prior to puberty.
      Compared to controls, treated monkeys showed sleep disruption, facilitated social
      interaction, greater impulsivity, and impaired sustained attention during
      treatment. No effects on growth were seen. Metabolomics assays characterized a
      distinctive response to fluoxetine and demonstrated individual differences that
      were related to the impulsivity measure. Fluoxetine interactions with monoamine
      oxidase A polymorphisms that influenced behavior and metabolomics markers were an
      important, previously unrecognized finding of our studies. After treatment was
      discontinued, some behavioral effects persisted, but short-term memory and
      cognitive flexibility testing did not show drug effects. This detailed
      experimental work can contribute to clinical research and continued safe and
      effective fluoxetine pharmacotherapy in children.

PMID- 29473032
TI  - Zein Nanoparticles and Strategies to Improve Colloidal Stability: A Mini-Review.
AB  - Zein, a protein extracted from maize, can be employed to easily produce nanoscale
      particles suitable for use as carrier systems. This review investigates the main
      methods for obtaining zein nanoparticles, as well as the problems and options
      available in the development of stable colloidal suspensions. Considerable gaps
      were identified in the literature concerning this topic, with studies being
      unclear about the factors that affect the stability of zein particles. In the
      vast majority of cases, no data are presented in relation to the stability of the
      formulations over time. It could be concluded that in order to produce a high
      quality system, detailed evaluation is required, considering factors including
      the zein concentration, pH, ionic strength, thermal treatment of the protein
      prior to preparation of the nanoparticles, strategies employing other materials
      as coatings, and the storage conditions. It is extremely important that these
      aspects should be considered during product development, prior to commercial
      scale manufacture.

PMID- 29473031
TI  - Find Cancer Early: Evaluation of a Community Education Campaign to Increase
      Awareness of Cancer Signs and Symptoms in People in Regional Western Australians.
AB  - Introduction: Cancer outcomes for people living in rural and remote areas are
      worse than for those living in urban areas. Although access to and quality of
      cancer treatment are important determinants of outcomes, delayed presentation has
      been observed in rural patients. Methods: Formative research with people from
      rural Western Australia (WA) led to the Find Cancer Early campaign. Find Cancer
      Early was delivered in three regions of WA, with two other regions acting as
      controls. Staff delivered the campaign using a community engagement approach,
      including promotion in local media. Television communications were not used to
      minimize contamination in the control regions. The campaign evaluation was
      undertaken at 20 months via a computer-assisted telephone interview (CATI) survey
      comparing campaign and control regions. The primary outcome variable was
      knowledge of cancer signs and symptoms. Results: Recognition and recall of Find
      Cancer Early and symptom knowledge were higher in the campaign regions. More than
      a quarter of those who were aware of the campaign reported seeing the GP as a
      result of their exposure. Conclusion: Despite limited use of mass media, Find
      Cancer Early successfully improved knowledge of cancer symptoms and possibly led
      to changes in behavior. Social marketing campaigns using community development
      can raise awareness and knowledge of a health issue in the absence of television
      advertising.

PMID- 29473033
TI  - Iron Based Catalysts Used in Water Treatment Assisted by Ultrasound: A Mini
      Review.
AB  - The characteristics and performances of catalyst are the key in catalytic
      ultrasonic treatment of wastewater, and iron based catalysts are known for low
      cost, high accessibility and safety. This paper reviewed the current research
      status of iron-based catalysts in water treatment assisted by ultrasound. Zero
      valent iron, Fe3O4 and iron composited with other metals were analyzed, their
      behaviors in catalytic sonochemistry were summarized, and the potential catalytic
      mechanisms were discussed in details. Finally, the future development in this
      field was proposed.

PMID- 29473034
TI  - Total Chemical Synthesis of Modified Histones.
AB  - In the post-genome era, epigenetics has received increasing attentions in recent
      years. The post-translational modifications (PTMs) of four core histones play
      central roles in epigenetic regulation of eukaryotic genome by either directly
      altering the biophysical properties of nucleosomes or by recruiting other
      effector proteins. In order to study the biological functions and structural
      mechanisms of these histone PTMs, an obligatory step is to prepare a sufficient
      amount of homogeneously modified histones. This task cannot be fully accomplished
      either by recombinant technology or enzymatic modification. In this context,
      synthetic chemists have developed novel protein synthetic tools and state-of-the
      art chemical ligation strategies for the preparation of homologous modified
      histones. In this review, we summarize the recent advances in the preparation of
      modified histones, focusing on the total chemical synthesis strategies. The
      importance and potential of synthetic chemistry for the study of histone code
      will be also discussed.

PMID- 29473036
TI  - Ethical and Philosophical Considerations for Gain-of-Function Policy: The
      Importance of Alternate Experiments.
AB  - The Department of Health and Human Services Framework for Guiding Funding
      Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens
      (PPPs) contains a series of principles for governing the funding and conduct of
      gain-of-function (GOF) research resulting in the creation of PPPs. In this
      article, I address one of these principles, governing the replacement of GOF
      research with alternate experiments. I argue that the principle fails to address
      the way that different experiments can promote the same values as those promoted
      by GOF research resulting in PPPs. I then address some objections to this claim,
      and provide policy recommendations moving forward.

PMID- 29473035
TI  - The Role of Noncoding RNA Pseudouridylation in Nuclear Gene Expression Events.
AB  - Pseudouridine is the most abundant internal RNA modification in stable noncoding
      RNAs (ncRNAs). It can be catalyzed by both RNA-dependent and RNA-independent
      mechanisms. Pseudouridylation impacts both the biochemical and biophysical
      properties of RNAs and thus influences RNA-mediated cellular processes. The
      investigation of nuclear-ncRNA pseudouridylation has demonstrated that it is
      critical for the proper control of multiple stages of gene expression regulation.
      Here, we review how nuclear-ncRNA pseudouridylation contributes to
      transcriptional regulation and pre-mRNA splicing.

PMID- 29473037
TI  - Regulation of ER-Golgi Transport Dynamics by GTPases in Budding Yeast.
AB  - A large number of proteins are synthesized de novo in the endoplasmic reticulum
      (ER). They are transported through the Golgi apparatus and then delivered to
      their proper destinations. The ER and the Golgi play a central role in protein
      processing and sorting and show dynamic features in their forms. Ras super family
      small GTPases mediate the protein transport through and between these organelles.
      The ER-localized GTPase, Sar1, facilitates the formation of COPII transport
      carriers at the ER exit sites (ERES) on the ER for the transport of cargo
      proteins from the ER to the Golgi. The Golgi-localized GTPase, Arf1, controls
      intra-Golgi, and Golgi-to-ER transport of cargo proteins by the formation of COPI
      carriers. Rab GTPases localized at the Golgi, which are responsible for fusion of
      membranes, are thought to establish the identities of compartments. Recent
      evidence suggests that these small GTPases regulate not only discrete sites for
      generation/fusion of transport carriers, but also membrane dynamics of the
      organelles where they locate to ensure the integrity of transport. Here we
      summarize the current understandings about the membrane traffic between these
      organelles and highlight the cutting-edge advances from super-resolution live
      imaging of budding yeast, Saccharomyces cerevisiae.

PMID- 29473038
TI  - Signaling through the Primary Cilium.
AB  - The presence of single, non-motile "primary" cilia on the surface of epithelial
      cells has been well described since the 1960s. However, for decades these
      organelles were believed to be vestigial, with no remaining function, having lost
      their motility. It wasn't until 2003, with the discovery that proteins
      responsible for transport along the primary cilium are essential for hedgehog
      signaling in mice, that the fundamental importance of primary cilia in signal
      transduction was realized. Little more than a decade later, it is now clear that
      the vast majority of signaling pathways in vertebrates function through the
      primary cilium. This has led to the adoption of the term "the cells's antenna" as
      a description for the primary cilium. Primary cilia are particularly important
      during development, playing fundamental roles in embryonic patterning and
      organogenesis, with a suite of inherited developmental disorders known as the
      "ciliopathies" resulting from mutations in genes encoding cilia proteins. This
      review summarizes our current understanding of the role of these fascinating
      organelles in a wide range of signaling pathways.

PMID- 29473040
TI  - Direct Immunofluorescence Using Non-Lesional Buccal Mucosa in Mucous Membrane
      Pemphigoid.
AB  - Mucous membrane pemphigoid (MMP) is a rare organ-specific autoimmune
      subepithelial blistering disease with predominantly mucosal erosions, most
      frequently affecting the gingiva. Erosions in the oral cavity usually result in
      markedly decreased quality of life. The major autoantigens are BP180 and
      laminin332, which are components of basement membrane proteins in the skin and
      mucosa. Diagnosis is usually difficult due to histological destruction of the
      tissue and low autoantibody titers. In this study, we evaluated the diagnostic
      value of direct immunofluorescence (DIF) using non-lesional buccal mucosa in
      seven cases of MMP. In all seven patients, gingival lesions were clinically
      observed, and in one of the seven patients, buccal lesions were also clinically
      observed. First, we performed DIF to detect tissue-bound autoantibodies and
      complement. DIF from non-lesional buccal mucosa revealed linear deposits of IgG
      and C3 at the basement membrane zone in all cases. To detect autoantibodies,
      indirect immunofluorescence (IIF), BP180-NC16A ELISA and immunoblotting were
      performed. Surprisingly, circulating autoantibodies were unable to be detected in
      any of the cases by ELISA, IIF, or immunoblotting. Furthermore, histological
      separation was observed in one patient. In conclusion, DIF using non-lesional
      buccal mucosa was found to be superior to histological and serological tests for
      diagnosing mucous membrane pemphigoid. The procedure is technically easy and has
      high diagnostic value.

PMID- 29473041
TI  - The Role of Statins in Disease Modification and Cardiovascular Risk in Rheumatoid
      Arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune, inflammatory disorder associated with
      excess cardiovascular morbidity and mortality. A complex interplay between
      traditional risk factors (dyslipidemia, insulin resistance, arterial
      hypertension, obesity, smoking) and chronic inflammation is implicated in the
      development of premature atherosclerosis and consequently in the higher incidence
      of cardiovascular events observed in RA patients. Despite the acknowledgment of
      elevated cardiovascular risk among RA individuals, its management remains
      suboptimal. While statin administration has a crucial role in primary and
      secondary cardiovascular disease prevention strategies as lipid modulating
      factors, there are limited data concerning the precise benefit of such therapy in
      patients with RA. Systemic inflammation and anti-inflammatory treatments
      influence lipid metabolism, leading to variable states of dyslipidemia in RA.
      Hence, the indications for statin therapy for cardiovascular prevention may
      differ between RA patients and the general population and the precise role of
      lipid lowering treatment in RA is yet to be established. Furthermore, some
      evidence supports a potential beneficial impact of statins on RA disease
      activity, attributable to their anti-inflammatory and immunomodulatory
      properties. This review discusses existing data on the efficacy of statins in
      reducing RA-related cardiovascular risk as well as their potential beneficial
      effects on disease activity.

PMID- 29473042
TI  - Combined Dietary Anthocyanins, Flavonols, and Stilbenoids Alleviate Inflammatory
      Bowel Disease Symptoms in Mice.
AB  - Dietary polyphenols are associated with a wide range of health benefits,
      protecting against chronic diseases and promoting healthy aging. Dietary
      polyphenols offer a complementary approach to the treatment of inflammatory bowel
      diseases (IBDs), a group of common chronic intestinal inflammation syndromes for
      which there is no cure. Tomato is widely consumed but its content of polyphenols
      is low. We developed a tomato variety, Bronze, enriched in three distinct classes
      of polyphenols: flavonols, anthocyanins, and stilbenoids. Using Bronze tomatoes
      as a dietary supplement as well as Indigo (high anthocyanins and flavonols),
      ResTom (high stilbenoids) and wild-type tomatoes, we examined the effects of the
      different polyphenols on the host gut microbiota, inflammatory responses, and the
      symptoms of chronic IBD, in a mouse model. Bronze tomatoes significantly impacted
      the symptoms of IBD. A similar result was observed using diets supplemented with
      red grape skin containing flavonols, anthocyanins, and stilbenoids, suggesting
      that effective protection is provided by different classes of polyphenols acting
      synergistically.

PMID- 29473043
TI  - Free Energy, Enthalpy and Entropy from Implicit Solvent End-Point Simulations.
AB  - Free energy is the key quantity to describe the thermodynamics of biological
      systems. In this perspective we consider the calculation of free energy, enthalpy
      and entropy from end-point molecular dynamics simulations. Since the enthalpy may
      be calculated as the ensemble average over equilibrated simulation snapshots the
      difficulties related to free energy calculation are ultimately related to the
      calculation of the entropy of the system and in particular of the solvent
      entropy. In the last two decades implicit solvent models have been used to
      circumvent the problem and to take into account solvent entropy implicitly in the
      solvation terms. More recently outstanding advancement in both implicit solvent
      models and in entropy calculations are making the goal of free energy estimation
      from end-point simulations more feasible than ever before. We review briefly the
      basic theory and discuss the advancements in light of practical applications.

PMID- 29473044
TI  - Cardiotoxicity of Anticancer Therapeutics.
AB  - As cancer therapeutics continues to improve and progress, the adverse side
      effects associated with anticancer treatments have also attracted more attention
      and have become extensively explored. Consequently, the importance of
      posttreatment follow-ups is becoming increasingly relevant to the discussion.
      Contemporary treatment methods, such as tyrosine kinase inhibitors, anthracycline
      chemotherapy, and immunotherapy regimens are effective in treating different
      modalities of cancers; however, these reagents act through interference with DNA
      replication or prevent DNA repair, causing endothelial dysfunction, generating
      reactive oxygen species, or eliciting non-specific immune responses. Therefore,
      cardiotoxic effects, such as hypertension, heart failure, and left ventricular
      dysfunction, arise posttreatment. Rising awareness of cardiovascular
      complications has led to meticulous attention for the evolution of treatment
      strategies and carefully monitoring between enhanced treatment effectiveness and
      minimization of adverse toxicity to the cardiovasculature, in which psychological
      assessments, early detection methods such as biomarkers, magnetic resonance
      imaging, and various drugs to reverse the damage from cardiotoxic events are more
      prevalent and their emphasis has increased tremendously. Fully understanding the
      mechanisms by which the risk factors action for various patients undergoing
      cancer treatment is also becoming more prevalent in preventing cardiotoxicity
      down the line.

PMID- 29473045
TI  - A Metabolomic Overview of Follicular Fluid in Cows.
AB  - Follicular fluid (FF) protects the oocyte against proteolysis and extrusion
      during ovulation, providing an appropriate microenvironment that favors proper
      embryonic development; thereby, FF plays a key role in embryo quality. Being
      directly related to cattle breeding, studying FF is extremely important in
      livestock science to measure cattle fertility. This may eventually help to assess
      the quality of both meat and milk, products widely consumed worldwide. There is
      an important commercial interest in the evaluation and characterization of
      compounds present in the FF of livestock that present greater likelihood of
      pregnancy. Mass spectrometry is a great ally for this type of analysis and can
      provide quick and efficient screening for molecular markers in biological
      samples. The present study demonstrated the potential of high-resolution mass
      spectrometry in analyzing FF samples from two distinct groups of Nellore cows
      (Bos indicus): high and low fertility, as determined by the number of oocytes
      produced. We were able to delineate markers of interest for each group, which may
      ultimately be related to biochemical pathways that lead to higher or lower
      reproductive performance.

PMID- 29473046
TI  - Duplications at 19q13.33 in patients with neurodevelopmental disorders.
AB  - Objective: After the recent publication of the first patients with disease
      associated missense variants in the GRIN2D gene, we evaluate the effect of copy
      number variants (CNVs) overlapping this gene toward the presentation of
      neurodevelopmental disorders (NDDs). Methods: We explored ClinVar (number of CNVs
      = 50,794) and DECIPHER (number of CNVs = 28,085) clinical databases of genomic
      variations for patients with copy number changes overlapping the GRIN2D gene at
      the 19q13.33 locus and evaluated their respective phenotype alongside their
      frequency, gene content, and expression, with publicly available reference
      databases. Results: We identified 11 patients with microduplications at the
      19q13.33 locus. The majority of CNVs arose de novo, and comparable CNVs are not
      present in control databases. All patients were reported to have NDDs and
      dysmorphic features as the most common clinical phenotype (N = 8/11), followed by
      seizures (N = 6/11) and intellectual disability (N = 5/11). All duplications
      shared a consensus region of 405 kb overlapping 13 genes. After screening for
      duplication tolerance in control populations, positive gene brain expression, and
      gene dosage sensitivity analysis, we highlight 4 genes for future evaluation:
      CARD8, C19orf68, KDELR1, and GRIN2D, which are promising candidates for disease
      causality. Furthermore, investigation of the literature especially supports
      GRIN2D as the best candidate gene. Conclusions: Our study presents dup19q13.33 as
      a novel duplication syndrome locus associated with NDDs. CARD8, C19orf68, KDELR1,
      and GRIN2D are promising candidates for functional follow-up.

PMID- 29473047
TI  - Familial monophasic acute transverse myelitis due to the pathogenic variant in
      VPS37A.
AB  - Objective: To identify genetic differences among siblings with a family history
      of idiopathic transverse myelitis (ITM). Methods: We compared whole-exome
      sequencing (WES) on germline samples from the 2 affected sisters with ITM with 3
      of their healthy siblings. Results: The 2 sisters with ITM both had acute onset
      of sensory loss in the legs, weakness, and bowel/bladder dysfunction. The first
      developed ITM at age 15 years with a clinical nadir of complete paralysis, which
      slowly recovered over a few years. MRI demonstrated a persistent T2 lesion in the
      lower thoracic cord. The second developed ITM at age 50 years with a nadir of
      sensory loss from T6 down and paraparesis in the legs, associated with an MRI
      lesion at T6. She also made a partial recovery with treatment. Both sisters are
      homozygous for a missense variant in VPS37A (c.700C>A, p.Leu234Ile) identified by
      WES. We performed targeted sequencing of VPS37A in an additional 86 samples from
      patients with ITM and 175 with other diseases to investigate the p.Leu234Ile
      variant. We identified another patient with ITM homozygous for the same rare
      variant. No patients with multiple sclerosis, neuromyelitis optica, other
      neurologic conditions, or any healthy controls in public databases were
      homozygous for this variant. Conclusions: A rare missense variant in VPS37A may
      predispose to development of ITM. Further studies are necessary to determine the
      frequency of this variant in the patient population and the mechanism through
      which it contributes to the risk of disease.

PMID- 29473048
TI  - Expanding the ADCY5 phenotype toward spastic paraparesis: A mutation in the M2
      domain.

PMID- 29473049
TI  - Late-onset and acute presentation of Brown-Vialetto-Van Laere syndrome in a
      Brazilian family.

PMID- 29473039
TI  - Surfactant Protein D in Respiratory and Non-Respiratory Diseases.
AB  - Surfactant protein D (SP-D) is a multimeric collectin that is involved in innate
      immune defense and expressed in pulmonary, as well as non-pulmonary, epithelia.
      SP-D exerts antimicrobial effects and dampens inflammation through direct
      microbial interactions and modulation of host cell responses via a series of
      cellular receptors. However, low protein concentrations, genetic variation,
      biochemical modification, and proteolytic breakdown can induce decomposition of
      multimeric SP-D into low-molecular weight forms, which may induce pro
      inflammatory SP-D signaling. Multimeric SP-D can decompose into trimeric SP-D,
      and this process, and total SP-D levels, are partly determined by variation
      within the SP-D gene, SFTPD. SP-D has been implicated in the development of
      respiratory diseases including respiratory distress syndrome, bronchopulmonary
      dysplasia, allergic asthma, and chronic obstructive pulmonary disease. Disease
      induced breakdown or modifications of SP-D facilitate its systemic leakage from
      the lung, and circulatory SP-D is a promising biomarker for lung injury.
      Moreover, studies in preclinical animal models have demonstrated that local
      pulmonary treatment with recombinant SP-D is beneficial in these diseases. In
      recent years, SP-D has been shown to exert antimicrobial and anti-inflammatory
      effects in various non-pulmonary organs and to have effects on lipid metabolism
      and pro-inflammatory effects in vessel walls, which enhance the risk of
      atherosclerosis. A common SFTPD polymorphism is associated with atherosclerosis
      and diabetes, and SP-D has been associated with metabolic disorders because of
      its effects in the endothelium and adipocytes and its obesity-dampening
      properties. This review summarizes and discusses the reported genetic
      associations of SP-D with disease and the clinical utility of circulating SP-D
      for respiratory disease prognosis. Moreover, basic research on the mechanistic
      links between SP-D and respiratory, cardiovascular, and metabolic diseases is
      summarized. Perspectives on the development of SP-D therapy are addressed.

PMID- 29473050
TI  - CYP2C19 variant mitigates Alzheimer disease pathophysiology in vivo and
      postmortem.
AB  - Objective: To verify whether CYP polymorphisms are associated with amyloid-beta
      (Abeta) pathology across the spectrum of clinical Alzheimer disease using in vivo
      and postmortem data from 2 independent cohorts. Methods: A candidate-gene
      approach tested the association between 5 genes (28 single nucleotide
      polymorphisms) and Abeta load measured in vivo by the global [18F]florbetapir PET
      standardized uptake value ratio (SUVR) in 338 Alzheimer's Disease Neuroimaging
      Initiative participants. Significant results were then tested using plasma Abeta
      and CSF Abeta and Abeta/phosphorylated tau (Abeta/p-tau) ratio in the same
      cohort. The significant association was also generalized to postmortem Abeta load
      measurement in the Rush Religious Orders Study/Memory and Aging Project cohorts.
      In addition, global cognition was used as a phenotype in the analysis in both
      cohorts. Results: Analysis of Abeta PET identified a variant in the CYP2C19 gene
      (rs4388808; p = 0.0006), in which carriers of the minor allele (MA) had a lower
      global SUVR. A voxel-wise analysis revealed that the variant is associated with a
      lower Abeta load in the frontal, inferior temporal, and posterior cingulate
      cortices. MA carriers also had higher CSF Abeta (p = 0.003) and Abeta/p-tau ratio
      (p = 0.02) but had no association with Abeta plasma levels. In postmortem brains,
      MA carriers had a lower Abeta load (p = 0.03). Global cognition was higher in MA
      carriers, which was found to be mediated by Abeta. Conclusions: Together, these
      findings point to an association between CYP2C19 polymorphism and Abeta
      pathology, suggesting a protective effect of the MA of rs4388808. Despite the
      several possibilities in which CYP2C19 affects brain Abeta, the biological
      mechanism by which this genetic variation may act as a protective factor merits
      further investigation.

PMID- 29473052
TI  - Novel hemizygous nonsense mutation in DRP2 is associated with inherited
      neuropathy.

PMID- 29473051
TI  - AP4 deficiency: A novel form of neurodegeneration with brain iron accumulation?
AB  - Objective: To describe the clinico-radiological phenotype of 3 patients harboring
      a homozygous novel AP4M1 pathogenic mutation. Methods: The 3 patients from an
      inbred family who exhibited early-onset developmental delay, tetraparesis,
      juvenile motor function deterioration, and intellectual deficiency were
      investigated by magnetic brain imaging using T1-weighted, T2-weighted, T2*
      weighted, fluid-attenuated inversion recovery, susceptibility weighted imaging
      (SWI) sequences. Whole-exome sequencing was performed on the 3 patients. Results:
      In the 3 patients, brain imaging identified the same pattern of bilateral SWI
      hyposignal of the globus pallidus, concordant with iron accumulation. A novel
      homozygous nonsense mutation was identified in AP4M1, segregating with the
      disease and leading to truncation of half of the adap domain of the protein.
      Conclusions: Our results suggest that AP4M1 represents a new candidate gene that
      should be considered in the neurodegeneration with brain iron accumulation (NBIA)
      spectrum of disorders and highlight the intersections between hereditary spastic
      paraplegia and NBIA clinical presentations.

PMID- 29473053
TI  - Dalfampridine is associated with de novo occurrence or reoccurrence of positive
      sensory symptoms in MS.

PMID- 29473054
TI  - Computed tomography scanning and stroke mortality in an urban medical unit in
      Cameroon.
AB  - Background: Despite the increasing availability of head computerized tomography
      (CT) in resource-limited settings, it is unclear if brain-imaging-based diagnosis
      of stroke affects the outcomes in the absence of dedicated structures for acute
      stroke management. Objectives: In a major referral hospital in the capital city
      of Cameroon, we compared in-hospital mortality rates in patients with a WHO-based
      diagnosis of stroke between participants with and without brain imaging on
      admission. Methods: Stroke patients with and without admission brain imaging were
      compared for demographic characteristics, risk factors, clinical and laboratory
      characteristic, and in-hospital mortality. Heterogeneities in mortality rates (CT
      vs. No CT) across major subgroups were investigated via interaction tests, and
      logistic regressions used to adjust for extraneous factors such as age, sex, year
      of study, residency, history of diabetes and hypertension, history of stroke,
      Glasgow coma scale, and delay between stroke symptoms onset and hospital
      admission. Results: Of the 1688 participants included in the final analysis, 1048
      (62.1%) had brain imaging. The median age of the non-CT vs. CT groups was 65 vs.
      62 years (p-value < 0.0001%). The death rate of non-CT vs. CT groups was 27.5%
      vs. 16.4% (p < 0.0001). This difference was mostly similar across major
      subgroups, and robust to the adjustments for confounders (in spite of substantial
      attenuation), with excess deaths in those with CT ranging from 65% to 149%.
      Conclusion: In this resource-limited environment, the absence of brain imaging on
      admission was associated with high in-hospital death from stroke, which was only
      partially explained by delayed hospitalization with severe disease. These results
      stressed the importance of scaling up acute stroke management in low- and middle
      income countries.

PMID- 29473055
TI  - MPV17-related hepatocerebral mitochondrial DNA depletion syndrome (MPV17-NNH)
      revisited.
AB  - MPV17-related hepatocerebral mitochondrial DNA depletion syndrome (previously
      known as Navajo neurohepatopathy) was discovered in children in the Four Corner's
      region of New Mexico approximately 40 years ago. This disease is associated with
      a single missense mutation in exon 2 in the MPV17 gene. The syndrome has now been
      recognized world-wide. We find that huge quantities of neurotoxins were present
      in archived nervous tissues from such patients. Arsenic was increased 18 *,
      cadmium ~ 10 *, cobalt 2.5 * and manganese 2.3 *; the largest increase was in
      mercury content 16,000 * compared to contemporaneous fresh-frozen normal nervous
      tissues. In the Four Corner's region of NM the life span is reduced compared to
      other parts of the United States and in our patients with MPV17-NNH the average
      life span was 5.4 years +/- 2.7 (SE) years. We now live in the Anthropocene an
      epoch characterized by large additions to the biosphere of neurotoxins. The
      effects of such toxic loads on human health and disease remain to be assessed. We
      speculate how such high neurotoxin content in tissues, which is likely to
      increase during the Anthropocene, may have influenced MPV17-NNH and similar
      phenotypes in different parts of the world. Our results imply that selenium
      supplementation to the diet in the Four Corner's region of NM might be beneficial
      to normal people and in the management of patients with MPV17-NNH syndrome.

PMID- 29473056
TI  - Testing cranial nerve VII: It is all in the wording.
AB  - During our practice of clinical neurological examination we frequently observed
      that patients, upon testing of cranial nerve VII, when instructed to "wrinkle
      their forehead" (to evaluate the innervation of the M. frontalis), seem to
      falsely "frown" (i.e. innervate the corrugator supercilii). Here, we set out to
      prospectively evaluate prevalence and characteristics of this phenomenon. Using a
      semi-structured questionnaire, we show that the majority of colleagues at our
      center shared our observation. Further, we demonstrate that of 113 unselected
      prospectively examined patients in fact 54.9% showed false frowning. This effect
      was irrespective of gender and only marginally influenced by age, chief complaint
      and clinical setting. Of note, all patients with initial frowning (or other
      "incorrect" reaction), when instructed to "raise their eye-brows", showed correct
      wrinkling. In summary, we were able to prospectively assess a highly prevalent
      artifact of the clinical exam, highlighting the critical significance of the
      correct wording during the neurological exam.

PMID- 29473057
TI  - Late-onset myasthenia gravis is predisposed to become generalized in the elderly.
AB  - Objective: The continuous increase in the number of patients presenting with late
      onset myasthenia gravis (LOMG) underscores the need for a better understanding of
      the clinical course and the establishment of an optimal therapeutic strategy. We
      aimed to clarify factors associated with clinical outcomes in LOMG. Methods: We
      retrospectively reviewed the clinical profiles of 40 patients with early-onset MG
      (EOMG) (onset age: 49 years or younger), 30 patients with non-elderly LOMG (onset
      age: 50-64 years), and 28 patients with elderly LOMG (onset age: 65 years or
      older) and compared the subgroups according to onset age and thymus status. The
      evaluated parameters were MGFA classification before treatment, MG-ADL score,
      complicating diseases, antibody titer, treatment, and MGFA post-intervention
      status. Results: Elderly LOMG patients showed transition to generalized symptoms
      at a higher frequency and underwent thymectomy less frequently than EOMG and non
      elderly LOMG patients (p < 0.001). The frequencies of crisis and plasmapheresis
      were significantly lower in thymectomized LOMG patients without thymoma than in
      thymectomized LOMG patients with thymoma or non-thymectomized LOMG patients (p <
      0.01, P < 0.05, respectively). However, the outcome was not significantly
      different. All of the thymectomized LOMG patients without thymoma presenting with
      hyperplasia or thymic cyst had a favorable clinical course. Conclusions: Our
      study showed that elderly LOMG patients are more prone to severity, suggesting
      that they require aggressive immunomodulatory therapy.

PMID- 29473059
TI  - Assessing Community Cancer care after insurance ExpanSionS (ACCESS) study
      protocol.
AB  - Background: Cancer is the second most common cause of mortality in the United
      States. Cancer screening and prevention services have contributed to improved
      overall cancer survival rates in the past 40 years. Vulnerable populations (i.e.,
      uninsured, low-income, and racial/ethnic minorities) are disproportionately
      affected by cancer, receive significantly fewer cancer prevention services,
      poorer healthcare, and subsequently lower survival rates than insured, white, non
      Hispanic populations. The Affordable Care Act (ACA) aims to provide health
      insurance to all low-income citizens and legal residents, including an expansion
      of Medicaid eligibility for those earning <=138% of federal poverty level. As of
      2012, Medicaid was expanded in 32 states and the District of Columbia, while 18
      states did not expand, creating a 'natural experiment' to assess the impact of
      Medicaid expansion on cancer prevention and care. Methods: We will use electronic
      health record data from up to 990 community health centers available up to 24
      months before and at least one year after Medicaid expansion. Primary outcomes
      include health insurance and coverage status, and type of insurance. Additional
      outcomes include healthcare delivery, number and types of encounters, and receipt
      of cancer prevention and screening for all patients and preventive care and
      screening services for cancer survivors. Discussion: Cancer morbidity and
      mortality is greatly reduced through screening and prevention, but uninsured
      patients are much less likely than insured patients to receive these services as
      recommended. This natural policy experiment will provide valuable information
      about cancer-related healthcare services as the US tackles the distribution of
      healthcare resources and future health reform. Trial Registration:
      Clinicaltrails.gov identifier NCT02936609.

PMID- 29473060
TI  - The life of proteins under mechanical force.
AB  - Although much of our understanding of protein folding comes from studies of
      isolated protein domains in bulk, in the cellular environment the intervention of
      external molecular machines is essential during the protein life cycle. During
      the past decade single molecule force spectroscopy techniques have been extremely
      useful to deepen our understanding of these interventional molecular processes,
      as they allow for monitoring and manipulating mechanochemical events in
      individual protein molecules. Here, we review some of the critical steps in the
      protein life cycle, starting with the biosynthesis of the nascent polypeptide
      chain in the ribosome, continuing with the folding supported by chaperones and
      the translocation into different cell compartments, and ending with proteolysis
      in the proteasome. Along these steps, proteins experience molecular forces often
      combined with chemical transformations, affecting their folding and structure,
      which are measured or mimicked in the laboratory by the application of force with
      a single molecule apparatus. These mechanochemical reactions can potentially be
      used as targets for fighting against diseases. Inspired by these insightful
      experiments, we devise an outlook on the emerging field of mechanopharmacology,
      which reflects an alternative paradigm for drug design.

PMID- 29473058
TI  - Prevention, management, and rehabilitation of stroke in low- and middle-income
      countries.
AB  - Although stroke incidence in high-income countries (HICs) decreased over the past
      four decades, it increased dramatically in low- and middle-income countries
      (LMICs). In this review, we describe the current status of primary prevention,
      treatment, and management of acute stroke and secondary prevention of and
      rehabilitation after stroke in LMICs. Although surveillance, screening, and
      accurate diagnosis are important for stroke prevention, LMICs face challenges in
      these areas due to lack of resources, awareness, and technical capacity.
      Maintaining a healthy lifestyle, such as no tobacco use, healthful diet, and
      physical activity are important strategies for both primary and secondary
      prevention of stroke. Controlling high blood pressure is also critically
      important in the general population and in the acute stage of hemorrhagic stroke.
      Additional primary prevention strategies include community-based education
      programs, polypill, prevention and management of atrial fibrillation, and digital
      health technology. For treatment of stroke during the acute stage, specific
      surgical procedures and medications are recommended, and inpatient stroke care
      units have been proven to provide high quality care. Patients with a chronic
      condition like stroke may require lifelong pharmaceutical treatment, lifestyle
      maintenance and self-management skills, and caregiver and family support, in
      order to achieve optimal health outcomes. Rehabilitation improves physical,
      speech, and cognitive functioning of disabled stroke patients. It is expected
      that home- or community-based services and tele-rehabilitation may hold special
      promise for stroke patients in LMICs.

PMID- 29473061
TI  - First-principles study of intrinsic defects in formamidinium lead triiodide
      perovskite solar cell absorbers.
AB  - As an alternative to methylammonium lead triiodide (MAPbI3), formamidinium lead
      triiodide (FAPbI3) perovskites have recently attracted significant attention
      because of their higher stability and smaller band gaps. Here, based on first
      principles calculations, we investigate systematically the intrinsic defects in
      FAPbI3. While methylammonium (MA)-related defects MAI and IMA in MAPbI3 have high
      formation energies, we found that formamidinium (FA)-related defects VFA, FAI and
      IFA in FAPbI3 have much lower formation energies. Antisites FAI and IFA create
      deep levels in the band gap, and they can act as recombination centers and result
      in reduced carrier lifetimes and low open circuit voltages in FAPbI3-based
      photovoltaic devices. We further demonstrate that through cation mixing of MA and
      FA in perovskites the formation of these defects can be substantially suppressed.

PMID- 29473062
TI  - An ultrasensitive microchip electrophoresis assay based on separation-assisted
      double cycling signal amplification strategy for microRNA detection in cell
      lysate.
AB  - Microchip electrophoresis (MCE) assay is an analysis technique with low
      consumption and high automation. It is a useful tool in biomedical research and
      clinical diagnosis. However, the low detection sensitivity limits its application
      in trace biomarker analysis because of its extremely small sample size. To
      address the need for high sensitivity in MCE, we have developed an ultrasensitive
      MCE method based on a separation-assisted double cycling signal amplification
      strategy for the detection of microRNA (miRNA) in cell lysate. In this method,
      two short single-stranded DNAs P1 and P2 complement each other to form a duplex
      DNA probe (P1/P2). In the presence of target miRNA, P2 in the P1/P2 probe can be
      displaced to form double-stranded miRNA/P1. Then, the degradation of P1 in
      miRNA/P1 by T7 Exo releases the miRNA, and the released miRNA participates in a
      displacement reaction with another P1/P2 probe to complete the first cycle. The
      displaced free P2 hybridizes with the hairpin fluorescence probe (MB) to form the
      P2/MB duplex, which can also be degraded by T7 Exo to release P2. The released P2
      can bind with another MB probe to complete the second cycle. By using MCE-laser
      induced fluorescence (LIF) as separation and detection platform and miRNA-141 as
      model analyte, the proposed MCE assay can detect miRNA-141 at concentrations as
      low as 8.0 fM, which is the highest sensitivity achieved to date for an MCE
      assay. This method for detecting trace miRNA holds great potential in biomedical
      research and clinical diagnosis.

PMID- 29473063
TI  - Synthesis and characterization of thallium-salen derivatives for use as
      underground fluid flow tracers.
AB  - A pair of thallium salen derivatives was synthesized and characterized for
      potential use as monitors (or taggants) or as models for Group 13 complexes for
      subterranean fluid flows. These precursors were isolated from the reaction of
      thallium ethoxide with N,N'-bis(3,5-di-tert-butylsalicylidene)-ethylenediamine
      (H2-salo-But), or N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-phenylenediamine
      (H2-saloPh-But). The products were identified by single crystal X-ray diffraction
      as: [((MU-O)2,kappa1-(N)(N')salo-But)Tl2] (1) and {[((MU-O)2saloPh-But)Tl2][((MU
      O)2,kappa1-(N)(N')saloPh-But)Tl2]} (2). Both structures are similar, wherein each
      O atom of the salo moiety bridges the two Tl atoms, leading to a TlTl
      interaction, which is further stabilized by an intramolecular pi-bond with
      neighboring phenyl rings. For 1, an additional TlN interaction was solved for
      each metal center; whereas, for 2, one of the two molecules in the matrix has a
      weak TlN interaction but no bonding noted in the other molecule. Both Density
      Functional Theory (DFT) calculations and variable temperature solution 205Tl NMR
      studies of 1 and 2 further confirmed the TlTl interaction. The UV-vis absorbance
      spectra of these compounds had an absorbance peak at 392 nm for 1 and a broad
      absorbance peak centered at 469 nm for 2, which were found to be in good
      agreement with the DFT calculated spectra that were dominated by the singlet
      state. Fluorescence emission and excitation studies reveal absorptions at 360 and
      380 nm for 1 and 2, respectively, which are attributed to the TlTl metal centers.
      To demonstrate practicality, fluorescence spectra of 1 and 2 were obtained using
      a handheld 405 nm cw laser pointer and portable spectrometer where compound 1 was
      found to glow 15 times brighter than compound 2. Only compound 1 was found to
      survive the simulated deep-well conditions explored, which was attributed to the
      TlN interaction noted for 1 but not for 2.

PMID- 29473064
TI  - Promiscuous hydrogen in polymerising plasmas.
AB  - Historically, there have been two opposing views regarding deposition mechanisms
      in plasma polymerisation, radical growth and direct ion deposition, with neither
      being able to fully explain the chemistry of the resultant coating. Deposition
      rate and film chemistry are dependent on the chemistry of the plasma phase and
      thus the activation mechanisms of species in the plasma are critical to
      understanding the relative contributions of various chemical and physical routes
      to plasma polymer formation. In this study, we investigate the roles that
      hydrogen plays in activating and deactivating reactive plasma species. Ethyl
      trimethylacetate (ETMA) is used as a representative organic precursor, and
      additional hydrogen is added to the plasma in the form of water and deuterium
      oxide. Optical emission spectroscopy confirms that atomic hydrogen is abundant in
      the plasma. Comparison of the plasma phase mass spectra of ETMA/H2O and ETMA/D2O
      reveals that (1) proton transfer from hydronium is a common route to charging
      precursors in plasma, and (2) hydrogen abstraction (activation) and recombination
      (deactivation) processes are much more dynamic in the plasma than previously
      thought. Consideration of the roles of hydrogen in plasma chemistry may then
      provide a more comprehensive view of deposition processes and bridge the divide
      between the two disparate schools of thought.

PMID- 29473065
TI  - A giant M2L3 metallo-organic helicate based on phthalocyanines as a host for
      electroactive molecules.
AB  - An unprecedented Fe2Pc3 metallo-organic helicate has been assembled using a
      bidentate phthalocyanine (Pc) ligand, 2-formylpyridine and Fe(OTf)2. This giant
      helicate has proved itself as a host for large redox-active guests such as
      fullerene and naphthalenediimide derivatives. Photoactivated electronic
      interactions between components occur in the host-guest complex.

PMID- 29473066
TI  - Mono- and dinuclear tetraphosphabutadiene ferrate anions.
AB  - Reduction of [CpArFe(MU-Br)]2 (1, CpAr = C5(C6H4-4-Et)5) by potassium
      napthalenide, followed by the addition of white phosphorus, affords [K(18-c
      6){CpArFe(eta4-P4)}] (2, 18-c-6 = [18]crown-6), which features a planar cyclo-P42
      ligand. The related diiron complex [Na2(THF)5(CpArFe)2(MU,eta4:4-P4)] (3) was
      obtained by reducing 1 with sodium amalgam in the presence of P4. Protonation of
      3 affords [Na(THF)3][(CpArFe)2(MU,eta4:4-P4)(H)] (4), while the reaction of 3
      with trimethylchlorosilane gives the nortricyclane compound P7(SiMe3)3 as the
      main product.

PMID- 29473067
TI  - Chemiluminescence molecular probe with intrinsic auto-inductive amplification:
      incorporation of chemiexcitation in a quinone-methide elimination.
AB  - A new signal amplification system with an auto-inductive mode of action and
      distinct chemiluminescence output was developed. The system is composed of a
      unique structural motif that combines a chemiexcitation mechanism with a quinone
      methide elimination into a signal building block. As demonstrated with a probe
      designed to detect fluoride, an auto-inductive chemiluminescence signal
      amplification was obtained through self-immolative disassembly and light emission
      mechanisms.

PMID- 29473068
TI  - A combinatorial approach towards the synthesis of non-hydrolysable triazole
      iduronic acid hybrid inhibitors of human alpha-l-iduronidase: discovery of enzyme
      stabilizers for the potential treatment of MPSI.
AB  - Preparation of substituent-diverse, triazole-iduronic acid hybrid molecules by
      click reaction of an azido iduronic acid derivative with randomly chosen alkynes
      is described. Library members were screened for their ability to inhibit alpha-l
      iduronidase, and hit molecules and analogues were then investigated for their
      ability to stabilize rh-alpha-IDUA in a thermal denaturation study. This work
      resulted in the discovery of the first small molecules that can be used to
      stabilize exogenous rh-alpha-IDUA protein in vitro.

PMID- 29473069
TI  - pH and generation dependent morphologies of PAMAM dendrimers on a graphene
      substrate.
AB  - The adsorption of PAMAM dendrimers at solid/water interfaces has been extensively
      studied, and is mainly driven by electrostatic and van der Waals interactions
      between the substrate and the dendrimers. However, the pH dependence of the
      adsorption driven predominantly by the van der Waals interactions is poorly
      explored, although it is crucial for investigating the potentiality of these
      dendrimers in supercapacitors and surface patterning. Motivated by this aspect,
      we have studied the adsorption behavior of PAMAM dendrimers of generations 2 (G2)
      to 5 (G5) with pH and salt concentration variation, on a charge neutral graphene
      substrate, using fully atomistic molecular dynamics simulations. The
      instantaneous snapshots from our simulations illustrate that the dendrimers
      deform significantly from their bulk structures. Based on various structural
      property calculations, we classify the adsorbed dendrimer morphologies into five
      categories and map them to a phase diagram. Interestingly, the morphologies we
      report here have striking analogies with those reported in star-polymer
      adsorption studies. From the fractional contacts and other structural property
      analyses we find that the deformations are more pronounced at neutral pH as
      compared to high and low pH. Higher generation dendrimers resist deformation
      following the deformation trend, G2 > G3 > G4 > G5 at any given pH level. As the
      adsorption here is mainly driven by van der Waals interactions, we observe no
      desorption of the dendrimers as the salt molarity is increased, unlike that
      reported in the electrostatically driven adsorption studies.

PMID- 29473070
TI  - Grape seed proanthocyanidins influence gut microbiota and enteroendocrine
      secretions in female rats.
AB  - Grape seed proanthocyanidin extract (GSPE) modulates several parameters involved
      in metabolic syndrome. GSPE is a mixture of compounds, some which are rapidly
      absorbed, while others remain in the lumen where they might have effects that are
      translated to the whole organism. Our aim was to decipher if the 8-day treatment
      of GSPE, previously shown to reduce food intake, induces changes in the
      microbiota and enterohormone secretion. The ratio of Firmicutes : Bacteroidetes
      was lower in the microbiota of GSPE-treated rats compared to controls, and
      differences in several taxonomic families and genera were observed. Such
      modulation led to a reduction in cecal butyrate content. GSPE also increased
      plasma glucagon-like-peptide-1 (GLP-1). Gallic acid did not induce major changes
      in the microbiota profile nor in GLP-1 secretion. Correlations between several
      microbiota taxa and plasma triacylglycerol, adiposity, and enterohormones were
      observed. Modulation of microbiota may be one of the mechanism by which GSPE
      impacts metabolic health.

PMID- 29473071
TI  - Spectroelectrochemical studies of a ruthenium complex containing the pH sensitive
      4,4'-dihydroxy-2,2'-bipyridine ligand.
AB  - Attaining high oxidation states at the metal center of transition metal complexes
      is a key design principle for many catalytic processes. One way to support high
      oxidation state chemistry is to utilize ligands that are electron-donating in
      nature. Understanding the structural and electronic changes of metal complexes as
      higher oxidation states are reached is critical towards designing more robust
      catalysts that are able to turn over at high rates without decomposing. To this
      end, we report herein the changes in structural and electronic properties as
      [Ru(bpy)2(44'bpy(OH)2)]2+ is oxidized to [Ru(bpy)2(44'bpy(OH)2)]3+ (bpy = 2,2'
      bipyridine; 44'bpy(OH)2 = 4,4'-dihydroxy-2,2'-bipyridine). The 44'bpy(OH)2 ligand
      is a pH-dependent ligand where deprotonation of the hydroxyl groups leads to
      significant electronic donation to the metal center. A Pourbaix Diagram of the
      complex reveals a pH independent reduction potential below pH = 2.0 for the
      Ru3+/2+ process at 0.91 V vs. Ag/AgCl. Above pH = 2.0, pH dependence is observed
      with a decrease in reduction potential until pH = 6.8 where the complex is
      completely deprotonated, resulting in a reduction potential of 0.62 V vs.
      Ag/AgCl. Spectroelectrochemical studies as a function of pH reveal the
      disappearance of the Metal to Ligand Charge Transfer (MLCT) or Mixed Metal-Ligand
      to Charge Transfer bands upon oxidation and the appearance of a new low energy
      band. DFT calculations for this low energy band were carried out using both B3LYP
      and M06-L functionals for all protonation states and suggest that numerous new
      transition types occur upon oxidation to Ru3+.

PMID- 29473072
TI  - Numerical-experimental observation of shape bistability of red blood cells
      flowing in a microchannel.
AB  - Red blood cells flowing through capillaries assume a wide variety of different
      shapes owing to their high deformability. Predicting the realized shapes is a
      complex field as they are determined by the intricate interplay between the flow
      conditions and the membrane mechanics. In this work we construct the shape phase
      diagram of a single red blood cell with a physiological viscosity ratio flowing
      in a microchannel. We use both experimental in vitro measurements as well as 3D
      numerical simulations to complement the respective other one. Numerically, we
      have easy control over the initial starting configuration and natural access to
      the full 3D shape. With this information we obtain the phase diagram as a
      function of initial position, starting shape and cell velocity. Experimentally,
      we measure the occurrence frequency of the different shapes as a function of the
      cell velocity to construct the experimental diagram which is in good agreement
      with the numerical observations. Two different major shapes are found, namely
      croissants and slippers. Notably, both shapes show coexistence at low (<1 mm s-1)
      and high velocities (>3 mm s-1) while in-between only croissants are stable. This
      pronounced bistability indicates that RBC shapes are not only determined by
      system parameters such as flow velocity or channel size, but also strongly depend
      on the initial conditions.

PMID- 29473073
TI  - Insights from ion mobility-mass spectrometry, infrared spectroscopy, and
      molecular dynamics simulations on nicotinamide adenine dinucleotide structural
      dynamics: NAD+vs. NADH.
AB  - Nicotinamide adenine dinucleotide (NAD) is found in all living cells where the
      oxidized (NAD+) and reduced (NADH) forms play important roles in many enzymatic
      reactions. However, little is known about NAD+ and NADH conformational changes
      and kinetics as a function of the cell environment. In the present work, an
      analytical workflow is utilized to study NAD+ and NADH dynamics as a function of
      the organic content in solution using fluorescence lifetime spectroscopy and in
      the gas-phase using trapped ion mobility spectrometry coupled to mass
      spectrometry (TIMS-MS) and infrared multiple photon dissociation (IRMPD)
      spectroscopy. NAD solution time decay studies showed a two-component
      distribution, assigned to changes from a "close" to "open" conformation with the
      increase of the organic content. NAD gas-phase studies using nESI-TIMS-MS
      displayed two ion mobility bands for NAD+ protonated and sodiated species, while
      four and two ion mobility bands were observed for NADH protonated and sodiated
      species, respectively. Changes in the mobility profiles were observed for NADH as
      a function of the starting solution conditions and the time after desolvation,
      while NAD+ profiles showed no dependence. IRMPD spectroscopy of NAD+ and NADH
      protonated species in the 800-1800 and 3200-3700 cm-1 spectral regions showed
      common and signature bands between the NAD forms. Candidate structures were
      proposed for NAD+ and NADH kinetically trapped intermediates of the protonated
      and sodiated species, based on their collision cross sections and IR profiles.
      Results showed that NAD+ and NADH species exist in open, stack, and closed
      conformations and that the driving force for conformational dynamics is hydrogen
      bonding of the N-H-O and O-H-O forms with ribose rings.

PMID- 29473074
TI  - Balancing silicon/aluminum oxide junctions for super-plasmonic emission
      enhancement of quantum dots via plasmonic metafilms.
AB  - We study the impact of structural features of Si/Al oxide junctions on metal
      oxide plasmonic metafilms formed via placing such junctions in close vicinity of
      an Au/Si Schottky barrier. The emission intensity and dynamics of colloidal
      semiconductor quantum dots deposited on such metafilms are investigated, while
      the surface morphology and structural compositions of the Si/Al oxide junction
      are controlled. The results show the conditions wherein the Si/Al oxide junction
      can reshape the impact of plasmonic effects, allowing it to increase the
      lifetimes of excitons. Under these conditions, the plasmonic metafilms can
      quarantine excitons against the fluctuating trap environments of the quantum
      dots, offering super-plasmonic emission enhancement that includes enhancement of
      the spontaneous emission decay rate combined with the suppression of Auger decay.

PMID- 29473076
TI  - Impact of cathepsin B-sensitive triggers and hydrophilic linkers on in vitro
      efficacy of novel site-specific antibody-drug conjugates.
AB  - Herein we describe the synthesis and evaluation of four novel HER2-targeting,
      cathepsin B-sensitive antibody-drug conjugates bearing a monomethylauristatin E
      (MMAE) cytotoxic payload, constructed via the conjugation of cleavable linkers to
      trastuzumab using a site-specific bioconjugation methodology. These linkers vary
      by both cleavable trigger motif and hydrophilicity, containing one of two
      cathepsin B sensitive dipeptides (Val-Cit and Val-Ala), and engendered with
      either hydrophilic or hydrophobic character via application of a PEG12 spacer.
      Through evaluation of physical properties, in vitro cytotoxicity, and receptor
      affinity of the resulting antibody-drug conjugates (ADCs), we have demonstrated
      that while both dipeptide triggers are effective, the increased hydrophobicity of
      the Val-Ala pair limits its utility within this type of linker. In addition,
      while PEGylation augments linker hydrophilicity, this change does not translate
      to more favourable ADC hydrophilicity or potency. While all described structures
      demonstrated excellent and similar in vitro cytotoxicity, the ADC with the
      ValCitPABMMAE linker shows the most promising combination of in vitro potency,
      structural homogeneity, and hydrophilicity, warranting further evaluation into
      its therapeutic potential.

PMID- 29473075
TI  - Monascin inhibits IL-1beta induced catabolism in mouse chondrocytes and
      ameliorates murine osteoarthritis.
AB  - Osteoarthritis (OA) is an age-related degenerative disease and is the fourth
      major cause of disability, but there are no effective therapies because of its
      complex pathology and the side effects of the drugs. Previous research
      demonstrated that inflammation and ECM degradation play major roles in OA
      development. Monascin is an azaphilonoid pigment extracted from Monascus
      fermented rice with a potential anti-inflammatory effect reported in various
      preclinical studies. In the present study, we investigated the protectiveness of
      monascin on interleukin (IL)-1beta-induced mouse chondrocytes and surgical
      destabilization of the medial meniscus mouse (DMM) OA models. In vitro, monascin
      treatment inhibited the IL-1beta-induced expression of cyclooxygenase-2 (COX-2),
      inducible nitric oxide synthase (iNOS), nitric oxide (NO), prostaglandin E2
      (PGE2), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6). In
      addition, the IL-1beta-stimulated matrix metalloproteinase-13 (MMP-13) and
      thrombospondin motifs 5 (ADAMTS-5) upregulation and type two collagen and
      aggrecan degradation were reversed by monascin. Mechanistically, we revealed that
      monascin suppressed nuclear factor kappa B (NF-kappaB) signalling by activating
      the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in IL-1beta-induced
      chondrocytes. And monascin-induced protectiveness in OA development was also
      shown by using a DMM model. Altogether, our results suggested that monascin could
      be a novel therapeutic approach for OA.

PMID- 29473077
TI  - Correction: Mechanical and thermal properties of grain boundary in a planar
      heterostructure of graphene and hexagonal boron nitride.
AB  - Correction for 'Mechanical and thermal properties of grain boundary in a planar
      heterostructure of graphene and hexagonal boron nitride' by Yinfeng Li, et al.,
      Nanoscale, 2018, DOI: 10.1039/c7nr07306b.

PMID- 29473083
TI  - Tandem radical cyclization for the construction of 1-difluoroalkylated
      isoquinolines via Cu catalyzed and visible light-promoted pathways.
AB  - A Cu/B2pin2 system promoted cyclization for the synthesis of 1-difluoroalkylated
      isoquinolines with vinyl isocyanides and bromodifluoroacetic derivatives in
      moderate to good yields was reported. This method provided a mild and efficient
      pathway for the construction of diverse 1-difluoroalkylated isoquinolines via a
      proposed tandem radical cyclization process.

PMID- 29473084
TI  - One-pot synthesis of thioesters with sodium thiosulfate as a sulfur surrogate
      under transition metal-free conditions.
AB  - In this paper, we report an efficient synthetic method for thioester formation
      from sodium thiosulfate pentahydrate, organic halides, and aryl anhydrides. In
      the one-pot two-step reactions developed in this study, sodium thiosulfate was
      used as the sulfur surrogate for acylation with anhydrides, followed by
      substitution with organic halides through the in situ generation of thioaroylate.
      Furthermore, two important organic compounds could be successfully synthesized
      using our developed method. The advantages of the one-pot two-step reactions are
      operational simplicity, structurally diverse products with 42%-90% yields, use of
      relatively low toxic and odourless reagents, and easy applicability to large
      scale operation.

PMID- 29473085
TI  - Crystallographic orientation of facets and planar defects in functional
      nanostructures elucidated by nano-focused coherent diffractive X-ray imaging.
AB  - The physical and chemical properties of nanostructures depend on their surface
      facets. Here, we exploit a pole figure approach to determine the three
      dimensional orientation matrix of a nanostructure from a single Bragg reflection
      measured with a coherent nano-focused X-ray beam. The signature of any truncated
      (faceted) crystal produces a crystal truncation rod, which corresponds to a
      streak of intensity in reciprocal space normal to the surface. When two or more
      non-parallel facets are present, both the crystal orientation and the crystal
      facets can be identified. This enables facets to be rapidly indexed and uncommon
      facets, and planar defects, that have been difficult to study before to be
      identified. We demonstrate the technique with (i) epitaxial core-shell InGaN/GaN
      multiple quantum-wells grown on GaN nanowires, where surface facets and planar
      defects are determined, and (ii) single randomly oriented highly faceted
      tetrahedrahexal Pt nanoparticles. The methodology is applicable to a broad range
      of nanocrystals and provides a unique insight into the connection between
      structure and properties of nanomaterials.

PMID- 29473086
TI  - Phase and composition controlled synthesis of cobalt sulfide hollow nanospheres
      for electrocatalytic water splitting.
AB  - Developing cheap, highly efficient and stable electrocatalysts for both oxygen
      and hydrogen evolution reactions (OER and HER) is extremely meaningful to realize
      large-scale implementation of water splitting technology. Herein, we report the
      phase and composition controlled synthesis of cobalt sulfide (CoSx) hollow
      nanospheres (HNSs) and their catalytic efficiencies for hydrogen and oxygen
      evolution reactions in alkaline media. Three CoSx compounds, i.e., Co9S8, Co3S4,
      and CoS2 HNSs, were precisely synthesized by simply adjusting the molar ratio of
      carbon disulfide to cobalt acetate using a facile solution-based strategy.
      Electrochemical results reveal that the as-prepared CoS2 HNSs exhibit superior
      OER and HER catalytic performance to Co9S8 and Co3S4 HNSs in 1.0 M KOH, with
      overpotentials of 290 mV for the OER and 193 mV for the HER at 10 mA cm-2, and
      the corresponding Tafel slopes of 57 and 100 mV dec-1, respectively. In addition,
      the CoS2 HNSs exhibit remarkable long-term catalytic durability, which is even
      superior to precious metal catalysts of RuO2 and Pt/C. Moreover, an alkaline
      electrolyzer assembled using CoS2 HNSs as both anode and cathode materials can
      achieve 10 mA cm-2 at a low cell voltage of 1.54 V at 60  degrees C with a
      faradaic efficiency of 100% for overall water splitting. Further analysis
      demonstrates that the surface morphology, crystallographic structure and
      coordination environment of Con+ active sites in combination determine the
      HER/OER activities in the synthesized binary CoSx series, which would provide
      insight into the rational design of transition metal chalcogenides for highly
      efficient hydrogen and oxygen-involved electrocatalysis.

PMID- 29473087
TI  - Diversity of metal-organic macrocycles assembled from carbazole based ligands
      with different lengths.
AB  - A series of carbazole based ligands with different lengths were assembled with
      nickel ions to construct metal-organic macrocycles. High-resolution mass
      spectrometry and ion mobility-mass spectrometry have been used to analyse the
      resulting MnLn assembly coexisting in solution. Combining with the structural
      analysis of their solid confirmation, it was revealed that the diversity of the
      metal-organic macrocycles was increased with the flexibility of the ligands.

PMID- 29473088
TI  - A glimpse into the regulation of the Wilson disease protein, ATP7B, sheds light
      on the complexity of mammalian apical trafficking pathways.
AB  - Wilson disease (WD), a Mendelian disorder of copper metabolism caused by
      mutations in the ATP7B gene, manifests a large spectrum of phenotypic
      variability. This phenomenon of extensive symptom variation is not frequently
      associated with a monogenic disorder. We hypothesize that the phenotypic
      variability in WD is primarily driven by the variations in interacting proteins
      that regulate the ATP7B function and localization in the cell. Based on existing
      literature, we delineated a potential molecular mechanism for ATP7B mediated
      copper transport in the milieu of its interactome, its dysfunction in WD and the
      resulting variability in the phenotypic manifestation. Understanding the copper
      induced apical trafficking of ATP7B also significantly contributes to the
      appreciation of the complexities of the ligand-induced transport pathway. We
      believe that this holistic view of WD will pave the way for a better opportunity
      for rational drug design and therapeutics.

PMID- 29473089
TI  - The Effects of Cariprazine and Aripiprazole on PCP-Induced Deficits on Attention
      Assessed in the 5-Choice Serial Reaction Time Task.
AB  - RATIONALE: Attentional processing deficits are a core feature of schizophrenia,
      likely contributing to the persistent functional and occupational disability
      observed in patients with schizophrenia. The pathophysiology of schizophrenia is
      hypothesized to involve dysregulation of NMDA receptor-mediated glutamate
      transmission, contributing to disruptions in normal dopamine transmission.
      Preclinical investigations often use NMDA receptor antagonists, such as
      phencyclidine (PCP), to induce cognitive disruptions relevant to schizophrenia.
      We sought to test the ability of partial dopamine D2/D3 agonists, cariprazine and
      aripiprazole, to attenuate PCP-induced deficits in attentional performance.
      OBJECTIVES: The objective of this study is to determine whether systemic
      administration of cariprazine or aripiprazole attenuated 5-choice serial reaction
      time task (5-CSRTT) deficits induced by repeated exposure to PCP. METHODS: We
      utilized a repeated PCP-treatment regimen (2 mg/kg, subcutaneous [s.c.], once
      daily for 5 days) in rats to induce deficits in the 5-CSRTT. Rats were pre
      treated with cariprazine (0.03, 0.1, or 0.3 mg/kg, oral [p.o.]) or aripiprazole
      (1, 3, or 10 mg/kg, p.o.) to determine whether they prevented PCP-induced
      deficits in the 5-CSRTT performance. RESULTS: PCP treatment increased
      inappropriate responding in the 5-CSRTT, elevating incorrect, premature, and
      timeout responses. Cariprazine treatment reduced PCP-induced increases in
      inappropriate responding. However, at higher doses, cariprazine produced non
      specific response suppression, confounding interpretation of the attenuated PCP
      induced deficits. Aripiprazole treatment also attenuated PCP-induced deficits;
      however, unlike cariprazine treatment, aripiprazole reduced correct responding
      and increased omissions. CONCLUSIONS: Cariprazine and aripiprazole both
      demonstrated potential in attenuating PCP-induced deficits in the 5-CSRTT
      performance. While both compounds produced non-specific response suppression,
      these effects were absent when 0.03 mg/kg cariprazine was administered.

PMID- 29473090
TI  - Cloning, characterization, and molecular expression of gonadotropin receptors in
      European hake (Merluccius merluccius), a multiple-spawning species.
AB  - Teleosts have many spawning strategies and the hormonal control of gametogenesis
      is not well defined among the species or even, between sexes. To increase the
      knowledge of gonadotropin hormones, we studied the trend by gene expression of
      gonadotropin receptors in the follicles and testis at different maturity stages
      in the European hake (Merluccius merluccius), a multiple-spawning species. With
      this aim, fshr and lhr were sequenced, characterized, and their gene expression
      was quantified in oocytes and in testes at different maturity stages. The deduced
      amino acid sequences were used to phylogenetic studies and evidenced that both
      receptors are phylogenetically closed to other gadoid species. The gene
      expression of both receptors was poorly expressed in primary follicles, increased
      in vitellogenic follicles and to later decrease in hydrated oocytes. In testis,
      highest levels of lhr were detected during spermiation, while levels of fshr were
      constant. For the first time, a histological analysis was performed in European
      hake testes showing an unrestricted lobular testis. To better elucidate the
      mechanisms involved in the oogenesis of the European hake, the expression of
      estrogen receptor and cyp19a was also investigated displaying high levels in all
      classes of follicles. All these data allow to increase the knowledge on
      reproductive physiology of an important socioeconomical species and it seeks to
      shed more light on the role of the receptors here studied during gametogenesis of
      multiple-spawning fish.

PMID- 29473091
TI  - Mechanisms Through Which Supportive Relationships with Parents and Peers Mitigate
      Victimization, Depression and Internalizing Problems in Children Bullied by
      Peers.
AB  - This study investigated how supportive relationships with peers and parents
      protect children against ongoing victimization, internalizing problems and
      depression. The longitudinal data set tracked progress of 111 children recruited
      for the trial of Resilience Triple P, and previously bullied by peers. Informants
      included children, parents and teachers. Higher levels of facilitative parenting
      (warm parenting that supports peer relationships) and peer acceptance predicted
      lower later levels of both depression and victimization over time. Higher levels
      of child friendedness predicted lower levels of child reports of internalizing
      problems. Children's friendships, acceptance by same sex peers and facilitative
      parenting all played moderating roles in protecting against ongoing victimization
      and internalizing problems. Peer acceptance mediated the relationships between
      facilitative parenting and victimization. Facilitative parenting mediated the
      relationship between peer acceptance and depression. It was concluded that
      supportive relationships with parents and peers play important and complementary
      roles in protecting children against ongoing victimization and depression.

PMID- 29473092
TI  - Four-pulse transcranial magnetic stimulation using multiple conditioning inputs.
      Normative MEP responses.
AB  - A four-pulse pattern of transcranial magnetic stimulation (TMS) was compared to
      traditional dual-pulse TMS for its ability to modulate motor cortical
      excitability. This novel pattern consisted of a three-pulse train of subthreshold
      conditioning pulses followed by a suprathreshold test pulse (i.e., SC-T). The
      intervals between these superconditioning (SC) pulses (1, 3, or 6 ms) and the
      follow-on test pulse (1, 3, 10, or 25 ms) were varied, and the resultant MEPs
      were compared to those elicited by: (1) single-pulse TMS; and (2) dual-pulse
      conditioning-test (C-T) TMS with either short (3 ms) or long (10 ms) intervals to
      elicit short-interval intracortical inhibition (SICI) or intracortical
      facilitation (ICF), respectively. Testing included abductor pollicis brevis (APB)
      and tibialis anterior (TA) in 15 neurologically normal adults. For
      superconditioning inputs, 10 ms test intervals caused especially strong
      facilitation of the test MEP, while 1 ms test intervals were particularly
      effective at causing inhibition of the test response. For both muscles and across
      all subjects, the most effective of the 12 SC-T inputs tested for causing either
      facilitation or inhibition was-with rare exception-superior to the dual-pulse TMS
      input for causing facilitation (i.e., ICF) or inhibition (i.e., SICI), while the
      overall magnitude of effect was more pronounced in APB compared to TA.
      Nevertheless, after normalization, the impact of a superconditioning input train
      on the test MEP was similar in APB and TA muscles, suggesting similar mechanisms
      of action. Limited findings from a single subject with amyotrophic lateral
      sclerosis (ALS) are included to further illustrate the potential advantages of
      using a train of conditioning pulses preceding a TMS test pulse to selectively
      investigate abnormal motor cortical excitatory and inhibitory circuitry.

PMID- 29473093
TI  - Assessment of iodine uptake by pancreatic cancer following chemotherapy using
      dual-energy CT.
AB  - Pancreatic cancer remains a major health problem, and only less than 20% of
      patients have resectable disease at the time of initial diagnosis. Systemic
      chemotherapy is often used in the patients with borderline resectable, locally
      advanced unresectable disease and metastatic disease. CT is often used to assess
      for therapeutic response; however, conventional imaging including CT may not
      correctly reflect treatment response after chemotherapy. Dual-energy (DE) CT can
      acquire datasets at two different photon spectra in a single CT acquisition, and
      permits separating materials and extract iodine by applying a material
      decomposition algorithm. Quantitative iodine mapping may have an added value over
      conventional CT imaging for monitoring the treatment effects in patients with
      pancreatic cancer and potentially serve as a unique biomarker for treatment
      response. In this pictorial essay, we will review the technique for iodine
      quantification of pancreatic cancer by DECT and discuss our observations of
      iodine quantification at baseline and after systemic chemotherapy with
      conventional cytotoxic agents, and illustrate example cases.

PMID- 29473094
TI  - Additional muscular slip of the flexor digitorum longus muscle to the fifth toe.
AB  - Despite the fact that there are numerous reports on muscular variations in the
      sole of the foot, routine dissection in a formaldehyde-fixed cadaver revealed an
      accessory flexor digiti quinti muscle, which to the best of our knowledge is a
      very unusual variant. This was in the form of a slender, 38 mm long muscular
      slip, with a proximal and distal tendon extending from the common flexor
      digitorum longus tendinous plate out to the distal phalanx of the fifth toe. An
      associated finding was the absence of the musculotendinous portion of the flexor
      digitorum brevis to the same toe. A developmental explanation for this variation
      is presented. Clinical implications with regard to this anatomical condition may
      result in clawing of the fifth toe.

PMID- 29473095
TI  - CT-Guided Percutaneous Trans-scapular Lung Biopsy in the Diagnosis of Peripheral
      Pulmonary Lesion Nodules of the Superior Lobes Using Large Needles.

PMID- 29473096
TI  - Influence of gemcitabine chemotherapy on the microbiota of pancreatic cancer
      xenografted mice.
AB  - BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) represents the
      fourth cause of cancer-related death. We aimed to evaluate whether gemcitabine
      treatment shapes the gut microbiota in a model of PDAC xenografted mice.
      MATERIALS AND METHODS: Pancreatic cancer xenograft mice were subjected to
      gemcitabine injection once per week for 3 weeks to assess the tumor volume as
      compared to control mice injected with normal saline solution. The composition of
      fecal microbiota, the activation of NF-kB pathway in cancer tissues and the serum
      metabolomics were further analyzed. RESULTS: Gemcitabine considerably decreases
      the proportion of Gram- positive Firmicutes (from about 39 to 17%) and the Gram-
      negative Bacteroidetes (from 38 to 17%) which are the two dominant phyla in the
      gut of tumor-bearing control mice. This downshift was replaced by an increase of
      Proteobacteria (Escherichia coli and Aeromonas hydrophila) from 15 up to 32% and
      Verrucomicrobia (Akkermansia muciniphila) from 5 to 33% in the gut of drug
      receiving mice. An overall increase in inflammation-associated bacteria was
      observed upon gemcitabine. Consistently, activation of the NF-kB canonical
      pathway was found in cancer tissues from gemcitabine-treated mice. Serum
      metabolomics revealed a significant decrease of the purine compounds inosine and
      xanthine, and a decreasing trend for their metabolically-related molecule
      hypoxanthine. DISCUSSION: Understanding chemotherapy side effects may explain the
      lack of activity or the chemoresistant processes and it may help to set up
      strategies to improve the effectiveness of therapy.

PMID- 29473097
TI  - Correction to: A phase I-II study of plerixafor in combination with fludarabine,
      idarubicin, cytarabine, and G-CSF (PLERIFLAG regimen) for the treatment of
      patients with the first early-relapsed or refractory acute myeloid leukemia.
AB  - The name of Pau Montesinos was inadvertently presented as Pau Montesinos
      Fernandez in the original article.The original version of this article was
      revised: The name of Pau Montesinos was inadvertently presented as Pau Montesinos
      Fernandez.

PMID- 29473098
TI  - Ischemic heart disease and ankylosing spondylitis-assessing the role of
      inflammation.
AB  - To assess the association of ankylosing spondylitis (AS) and ischemic heart
      disease (IHD) compared to traditional cardiovascular (CV) risk factors. Primary
      care and hospital records of patients with AS were analyzed, using the largest
      health maintenance organization in Israel, the "Clalit" Health Services data.
      These patients were compared with age- and gender-matched controls regarding the
      proportion of IHD in a cross-sectional study. Parameters including socioeconomic
      status, body mass index (BMI), smoking habits, and coexistent medical conditions
      hypertension, hyperlipidemia, and diabetes mellitus (DM) - as well as the use of
      NSAIDs and anti-TNFs were also assessed. The study included 4076 AS patients
      compared to 20,290 age- and gender-matched controls without AS. The proportion of
      IHD was higher among AS patients as compared to controls (14.1 vs. 6.36%,
      respectively, p < 0.01) and patients treated with anti-TNFs had a lower risk for
      IHD compared to non-anti-TNF users. The proportion of hypertension,
      hyperlipidemia, DM, and smoking was also higher among AS patients. However, in
      multivariate analyses following adjustment to these risk factors, AS was not
      found to be associated with IHD nor anti-TNF therapy to be a protective factor.
      Patients with AS have more traditional CV risk factors, thus are in a higher risk
      for IHD. AS itself was not shown to be independently associated with IHD. These
      findings emphasize the multifactorial process leading to increased proportion of
      IHD among AS patients and the need for a stringent control of traditional risk
      factors in these patients.

PMID- 29473099
TI  - The filamentous fungal pellet-relationship between morphology and productivity.
AB  - Filamentous fungi are used for the production of a multitude of highly relevant
      biotechnological products like citric acid and penicillin. In submerged culture,
      fungi can either grow in dispersed form or as spherical pellets consisting of
      aggregated hyphal structures. Pellet morphology, process control and productivity
      are highly interlinked. On the one hand, process control in a bioreactor usually
      demands for compact and small pellets due to rheological issues. On the other
      hand, optimal productivity might be associated with less dense and larger
      morphology. Over the years, several publications have dealt with aforementioned
      relations within the confines of specific organisms and products. However,
      contributions which evaluate such interlinkages across several fungal species are
      scarce. For this purpose, we are looking into methods to manipulate fungal pellet
      morphology in relation to individual species and products. This review attempts
      to address (i) how variability of pellet morphology can be assessed and (ii) how
      morphology is linked to productivity. Firstly, the mechanism of pellet formation
      is outlined. Subsequently, the description and analysis of morphological
      variations are discussed to finally establish interlinkages between productivity,
      performance and morphology across different fungal species.

PMID- 29473100
TI  - The suspensor as a model system to study the mechanism of cell fate specification
      during early embryogenesis.
AB  - KEY MESSAGE: The advances in the suspensor. During early embryogenesis, the
      proembryo consists of two domains, the embryo proper and the suspensor. Unlike
      the embryo proper, which has been investigated extensively, research on the
      suspensor has been limited in past decades. Recent studies have revealed that the
      suspensor plays an important role in early embryogenesis and the process of
      suspensor formation and degeneration may provide a unique model for studies on
      cell division pattern, cell fate determination, and cell death. In this review,
      we briefly summarize the advances in research on the suspensor, which provide new
      insight in our understanding of the mechanism of early embryogenesis and show
      great potential for a unique model for future investigations.

PMID- 29473101
TI  - Cardiac Function Assessments in Left Bochdalek's Hernia: Clinical Relevance.
AB  - The objectives of this study were to characterize peri-operative
      echocardiographic (ECHO) assessments of right ventricular (RV) function and
      pulmonary hypertension (PH) and ascertain correlation with clinical outcomes in
      infants with left Bochdalek's hernia (LBH). This retrospective study in a
      quaternary neonatal intensive care unit involved electronic database search for
      infants with LBH during January 2009 to July 2017. Demographics, outcomes, and
      ECHO parameters were accessed from archived databases. Thirty-one infants with
      mean gestational age and birthweight (BW) 38.4 +/- 1.4 weeks and 3079 +/- 450 g
      were included. Postnatal age at surgery was 4.3 +/- 2 days. Two infants died
      before surgery (none after surgery). The survival rate in this cohort of late
      preterm and term infants with LBH not accompanied by congenital heart disease was
      29/31 (93.5%). PH was noted in 28 (90%). Significant changes in biventricular
      function and pulmonary vascular haemodynamics were noted when reassessed after
      surgery [RV area change (%), 28 +/- 3 vs. 34 +/- 4, p = 0.007 and pulmonary
      artery capacitance (PAC) (ml3 * mmHg-1), 0.05 +/- 0.03 vs. 0.09 +/- 0.05, p =
      0.02]. The median duration of all respiratory support in those who were operated
      was 14.7 days (8.5, 25). Significant correlations were noted between pre
      operative ECHO assessments and the duration of respiratory support (tricuspid
      regurgitation, r = 0.63, p = 0.0001 and PAC, r = - 0.52, p = 0.004). Peri
      operative functional ECHO provided information about the evolution of cardiac
      function in infants with LBH.

PMID- 29473102
TI  - Driving ban for diesel-powered vehicles in major cities: an appropriate penalty
      for exceeding the limit value for nitrogen dioxide?

PMID- 29473103
TI  - Considering Culture: A Review of Pediatric Behavioral Intervention Research in
      Type 1 Diabetes.
AB  - PURPOSE OF REVIEW: Type 1 diabetes (T1D) incidence in youth is growing across all
      racial/ethnic backgrounds, with the most marked increase in African-American
      youth under 5. Underrepresented racial/ethnic minorities are at an increased risk
      for health complications. This review focuses on the reported disparities,
      demographics of samples in behavioral interventions, and study design
      considerations. RECENT FINDINGS: Recruitment data from two ongoing behavioral
      intervention trials for young children with T1D are presented to compare
      enrolled/non-enrolled individuals and to discuss culturally appropriate study
      design considerations. Data were compared to the demographics of children (ages 1
      6) with T1D in the clinic populations from the recruitment sites. Enrolling a
      representative sample and designing culturally appropriate behavioral
      interventions are important for generalizability, yet there is a gap between the
      individuals participating in T1D research and those who are most negatively
      affected by T1D. Suggestions are offered for ways to expand inclusion of diverse
      samples in behavioral intervention research in T1D.

PMID- 29473104
TI  - Duration of acute kidney injury in critically ill patients.
AB  - BACKGROUND: Duration of acute kidney injury (AKI) has been recognized a risk
      factor for adverse outcomes following AKI. We sought to examine the relationship
      of AKI duration and recurrent AKI with short-term outcomes in critically ill
      patients who were mechanically ventilated and met criteria for the acute
      respiratory distress syndrome. METHODS: Participants in the NHLBI ARDS Network
      SAILS multicenter trial who developed AKI were included in this analysis and
      divided into groups based on AKI duration. Differences in outcomes were evaluated
      using t test and Chi-square test. Competing risks regression and Cox regression
      were used to evaluate factors associated with resolving AKI and recurrent AKI.
      RESULTS: In total, 238 patients were included in the study. Seventy-seven
      patients had short duration AKI (1-2 days), 47 medium duration AKI (3-7 days), 87
      persistent AKI (> 7 days) and 38 died during their AKI episode. Persistent AKI
      was associated with worse outcomes including increased ICU length of stay, time
      on the ventilator and days with cardiovascular failure. We found no clinical
      differences between patients with short and medium duration AKI, even when
      accounting for AKI severity and recurrent AKI. Patients with resolving AKI were
      less likely to have oliguria or moderate/severe ARDS on the day AKI criteria were
      met. Recurrent AKI was associated with poorer clinical outcomes. No baseline
      clinical factors were found to predict development of recurrent AKI. CONCLUSIONS:
      In critically ill patients with sepsis-associated ARDS and AKI, the impact of
      short and medium duration AKI on clinical outcomes was modest. Persistent and
      recurrent AKI were both associated with worse clinical outcomes, emphasizing the
      importance of identifying these patients, who may benefit from novel
      interventions.

PMID- 29473105
TI  - The use of throat packs in pediatric cleft lip/palate surgery: a retrospective
      study.
AB  - OBJECTIVES: Throat packs are commonly used to prevent ingestion or aspiration of
      blood and other debris during cleft lip/palate surgery. However, dislodgement or
      (partial) retainment after extubation could have serious consequences. The aim of
      the present study was to investigate the effect of omitting pharyngeal packing
      during cleft lip/palate surgery on the incidence of early postoperative
      complications in children. MATERIALS AND METHODS: A retrospective study was
      performed on all children who underwent cleft lip/palate surgery at the
      Wilhelmina Children's Hospital. This study compared the period January 2010
      through December 2012 when pharyngeal packing was applied according to local
      protocol (group A) with the period January 2013 till December 2015 when
      pharyngeal packing was no longer applied after removal from the protocol (group
      B). Data were collected for sex, age at operation, cleft lip/palate type, type of
      repair, lateral incisions, length of hospital stay, and complications in the
      first 6 weeks after surgery. Early complications included wound dehiscence,
      postoperative bleeding, infection, fever, upper respiratory tract infection
      (URTI), and lower respiratory tract infection (LRTI). RESULTS: This study
      included 489 cleft lip/palate operations (group A n = 246, group B n = 243). A
      total of 39 (15.9%) early complications were recorded in group A and a total of
      40 (16.5%) in group B. There were no significant differences (P = 0.902) in
      complications between the two groups; however, there was a significant difference
      (P < 0.001) in length of hospital stay between the two groups (group A 3.6 days
      vs group B 3.2 days). CONCLUSION: Omitting routine placement of throat packs in
      cleft lip/palate surgery was not associated with an increased early postoperative
      complication rate. Therefore, the traditional, routine placement of a throat pack
      during cleft lip/palate surgery can be questioned. CLINICAL RELEVANCE: The
      traditional, routine placement of a throat pack during cleft lip/palate surgery
      can be questioned.

PMID- 29473106
TI  - ATP6AP2 over-expression causes morphological alterations in the hippocampus and
      in hippocampus-related behaviour.
AB  - The (pro)renin receptor [(P)RR], also known as ATP6AP2 [ATPase 6 accessory
      protein 2], is highly expressed in the brain. ATP6AP2 plays a role in early brain
      development, adult hippocampal neurogenesis and in cognitive functions. Lack of
      ATP6AP2 has deleterious effects, and mutations of ATP6AP2 in humans are
      associated with, e.g. X-linked intellectual disability. However, little is known
      about the effects of over-expression of ATP6AP2 in the adult brain. We
      hypothesized that mice over-expressing ATP6AP2 in the brain might exhibit altered
      neuroanatomical features and behavioural responses. To this end, we investigated
      heterozygous transgenic female mice and confirmed increased levels of ATP6AP2 in
      the brain. Our data show that over-expression of ATP6AP2 does not affect adult
      hippocampal neurogenesis, exercise-induced cell proliferation, or dendritic spine
      densities in the hippocampus. Only a reduced ventricular volume on the gross
      morphological level was found. However, ATP6AP2 over-expressing mice displayed
      altered exploratory behaviour with respect to the hole-board and novel object
      recognition tests. Moreover, primary adult hippocampal neural stem cells over
      expressing ATP6AP2 exhibit a faster cell cycle progression and increased cell
      proliferation. Together, in contrast to the known deleterious effects of ATP6AP2
      depletion, a moderate over-expression results in moderate behavioural changes and
      affects cell proliferation rate in vitro.

PMID- 29473107
TI  - Reply to: "All that glitters is not gold - new reconstruction methods using
      Deauville criteria for patient reporting".

PMID- 29473108
TI  - Response to: Periosteal mesenchymal chondrosarcoma of the tibia.

PMID- 29473110
TI  - Finger-counting habits, not finger movements, predict simple arithmetic problem
      solving.
AB  - Previous research in embodied mathematical cognition has found differences
      between those who start counting on their left hand and those who start counting
      on the right hand. However, if starting hand is a finger-embodied effect, then
      finger-specific interference may affect these differences between left and right
      starters. Furthermore, cultures that demonstrate different finger-counting habits
      may also be differently affected by this interference. In the current study, a
      total of 66 Canadians and 60 Chinese participants completed a single/dual-task
      paradigm and were also assessed on their starting hand for counting. The primary
      task was to verbally answer simple arithmetic problems, while the dual task was
      to either sequentially tap their fingers or their foot. Contrary to predictions,
      a specific finger-movement interference pattern that had previously been reported
      was not evident in this study, despite a much larger sample. Nevertheless,
      Canadians left starters outperformed right starters for every operation type,
      which may be further evidence of individual differences in the lateralization of
      arithmetic processes. Derived from a combination of a replication, a conceptual
      replication, and a cross-cultural comparison, this investigation suggests that
      embodied effects in the published literature are in need of both independent
      replication as well as investigation of individual differences. This study also
      further validates the differences between left and right starters, and suggests
      that more research is needed to understand the influence of embodied cognition on
      mathematical understanding.

PMID- 29473111
TI  - Correction to: The effect of cationically-modified phosphorylcholine polymers on
      human osteoblasts in vitro and their effect on bone formation in vivo.
AB  - The article "The effect of cationically modified phosphorylcholine polymers on
      human osteoblasts in vitro and their effect on bone formation in vivo", written
      by Jonathan M. Lawton, Mariam Habib, Bingkui Ma, Roger A. Brooks, Serena M. Best,
      Andrew L. Lewis, Neil Rushton and William Bonfield, was originally published
      Online First without open access. After publication in volume 28, issue 9, page
      144 it was noticed that the copyright was wrong in the PDF version of the
      article. The copyright of the article should read as "

PMID- 29473112
TI  - A study of sensory dysregulation in children with tic disorders.
AB  - Disrupted somatosensory processing characterized by over- or under-
      responsiveness to environmental stimuli plays an important, yet often overlooked,
      role in typical development and is aberrant in various neurodevelopmental
      disorders. These dysfunctional somatosensory processes have been conceptualized
      as an entity termed somatosensory dysregulation (SMD). Since Tourette syndrome
      (TS) is a prototypical example of developmental psychopathological disorder, we
      hypothesised that SMD would be a feature found in children suffering from the
      disorder. Ninety-two subjects representing consecutive admissions to a tertiary
      paediatric Tourette syndrome clinic were admitted to the study. Comorbid
      conditions included ADHD, depression, anxiety disorder, and OCD. For purposes of
      the study, patients completed a battery of self-, caregiver-, and clinician-rated
      psychological instruments measuring TS core symptoms and comorbidities and
      quality of life. Sensory modulation was measured by self-report and by objective
      measures such as stimulation with Von Frey filaments. Almost 50% of the cohort
      had no SMD. Of the remainder, 14 (15%) had suspected SMD and 32 (34.8%) had SMD.
      SMD was significantly more common and severe when there were comorbidities. The
      presence of SMD was associated with more severe impairments in quality of life
      and less participation in daily activities. The SMD, as measured by subjective
      measures but not by objective, is probably more associated with central
      processing rather than peripheral perception.

PMID- 29473113
TI  - The Biocompatibility of Dental Graded Nano-Glass-Zirconia Material After Aging.
AB  - : ?: A graded nano-glass/zirconia (G/Z) system has been developed via the
      infiltration of nano-glass into a nano-zirconia surface, which is advantageous
      for robust core-veneer bonds. The aging issue is a key for yttrium-stabilized
      tetragonal zirconia polycrystals (Y-TZPs), and therefore, it is necessary to
      evaluate the influence of aging degradation on the biocompatibility of G/Z
      systems before their possible clinical application. Herein, such biocompatibility
      testing was performed with human gingival fibroblasts (HGFs) seeded onto
      unaged/aged G/Z and Y-TZP for 2-72 h. Assessments included an oral mucous
      membrane irritation test in conjunction with analyses of cell viability, cell
      adhesion, and oxidative stress responses. Significant metabolic decreases in aged
      G/Z- and Y-TZP-treated cells were observed at 72 h. G/Z did not elicit any
      significant differences in cell viability compared with Y-TZP over 72 h both
      before and after aging. The oxidative stress data for the aged G/Z- and Y-TZP
      treated cells showed a significant increase at 72 h. The G/Z specimens did not
      elicit any significant differences in ROS production compared with Y-TZP over 72
      h both before and after aging. The cell adhesion rates of both G/Z and Y-TZP
      increased significantly after aging. The cell adhesion rates of G/Z and Y-TZP
      were not significantly different before and after aging. According to the oral
      mucous membrane irritation test, scores for macroscopic and microscopic
      observations for both the aged G/Z and unaged G/Z sides were 0, demonstrating no
      consequent irritation. CONCLUSIONS: The excellent biocompatibility of G/Z
      indicates that it has potential for future clinical applications.

PMID- 29473114
TI  - Treatment of post-burn and post-traumatic atrophic scars with fractional CO2
      laser: experience at a tertiary care centre.
AB  - Scars are abnormal wound responses in predisposed individuals. They occur after
      any kind of wound and skin inflammation in predisposed individuals. Despite their
      benign nature, they can be aesthetically disabling. Although several approaches
      have been tried in their management, most of them have produced poor results.
      This study aims to assess the efficacy and safety of fractional CO2 laser
      treatment in the management of post-burn and post-traumatic scars. One hundred
      consecutive patients (77 females and 23 males) affected by post-burn scars as
      well as post-traumatic atrophic scars were treated with monthly sessions of
      fractional CO2 laser treatment. Patient's response to treatment was assessed
      clinically as well as improvement of scars by comparing the photographs taken
      before treatment with those taken 6 months after the last treatment session.
      Changes in skin texture, surface irregularity and pigmentation were assessed on a
      quartile grading scale and scored individually from 0 to 4. A mean of the three
      individual scores was calculated and the response was labelled as 'excellent' if
      the mean score achieved was > 3. A score of 2-3 was labelled as good response
      while a score below 1 was labelled as 'poor' response. A mean of six treatments
      per scar were required and all patients, followed up for 1 year after the last
      treatment, had optimum results and no recurrence. Response to treatment was
      excellent in 53.75%, good in 16.25% patients, and poor in 30% patients.
      Fractional CO2 laser gives a very good result in the management of patients with
      post-burn scars as well as post-traumatic scars with minimal adverse effects.

PMID- 29473115
TI  - The effects of exercise training associated with low-level laser therapy on
      biomarkers of adipose tissue transdifferentiation in obese women.
AB  - Investigations suggest the benefits of low-level laser therapy (LLLT) to improve
      noninvasive body contouring treatments, inflammation, insulin resistance and to
      reduce body fat. However, the mechanism for such potential effects in association
      with exercise training (ET) and possible implications in browning adiposity
      processes remains unclear. Forty-nine obese women were involved, aged between 20
      and 40 years with a body mass index (BMI) of 30-40 kg/m2. The volunteers were
      divided into Phototherapy (808 nm) and SHAM groups. Interventions consisted of
      exercise training and phototherapy applications post exercise for 4 months, with
      three sessions/week. Body composition, lipid profile, insulin resistance, atrial
      natriuretic peptide (ANP), WNT5 signaling, interleukin-6 (IL-6), and fibroblast
      growth factor-21 (FGF-21) were measured. Improvements in body mass, BMI, body fat
      mass, lean mass, visceral fat, waist circumference, insulin, HOMA-IR, total
      cholesterol, LDL-cholesterol, triglycerides, and ANP in both groups were
      demonstrated. Only the Phototherapy group showed a reduction in interleukin-6 and
      an increase in WNT5 signaling. In addition, it was possible to observe a higher
      magnitude change for the fat mass, insulin, HOMA-IR, and FGF-21 variables in the
      Phototherapy group. In the present investigation, it was demonstrated that
      exercise training associated with LLLT promotes an improvement in body
      composition and inflammatory processes as previously demonstrated. The
      Phototherapy group especially presented positive modifications of WNT5 signaling,
      FGF-21, and ANP, possible biomarkers associated with browning adiposity
      processes. This suggests that this kind of intervention promotes results
      applicable in clinical practice to control obesity and related comorbidities.

PMID- 29473116
TI  - Phytochemical variation in treetops: causes and consequences for tree-insect
      herbivore interactions.
AB  - The interaction of plants and their herbivorous opponents has shaped the
      evolution of an intricate network of defences and counter-defences for millions
      of years. The result is an astounding diversity of phytochemicals and plant
      strategies to fight and survive. Trees are specifically challenged to resist the
      plethora of abiotic and biotic stresses due to their dimension and longevity.
      Here, we review the recent literature on the consequences of phytochemical
      variation in trees on insect-tree-herbivore interactions. We discuss the
      importance of genotypic and phenotypic variation in tree defence against insects
      and suggest some molecular mechanisms that might bring about phytochemical
      diversity in crowns of individual trees.

PMID- 29473117
TI  - Relationship among symptom clusters, quality of life, and treatment-specific
      optimism in patients with cancer.
AB  - PURPOSE: There is increasing evidence that disease and therapy-related symptoms
      frequently co-occur in so-called symptom clusters (SCs), which may significantly
      impair quality of life in patients with cancer. Although psychosocial resources
      may play pivotal roles in maintaining or improving quality of life, they have
      been neglected in SC research. Therefore, we aim to identify SCs and their
      relative impact on quality of life when psychosocial resources are accounted for.
      METHODS: Patients with cancer (n = 304) undergoing chemotherapy or chemo
      radiation therapy participated in a cross-sectional survey consisting of measures
      assessing symptoms, quality of life, resilience, treatment-specific optimism
      (TSO), and social support. Exploratory factor analyses and multiple regression
      analyses were used to identify SCs and significant explanatory variables of
      overall quality of life. RESULTS: Fatigue-pain, anxiety-depression, cancer
      therapy-related toxicity, and nausea-vomiting clusters were identified. In our
      final model, the fatigue-pain cluster (beta = - 0.41, p < 0.001), nausea-vomiting
      cluster (beta = - 0.28, p < 0.001), TSO (beta = 0.21, p < 0.001), and receiving
      chemo-radiation treatment (beta = - 0.11, p = 0.03) accounted for 44% of variance
      in overall quality of life. However, the identified SCs explained quality of life
      in patients with varying levels of TSO to a different extent. CONCLUSIONS: Our
      findings indicate that the TSO of patients may be a major factor to consider in
      managing SCs, because-depending on its level-different SCs and even clusters
      encompassing comparatively less distressing symptoms (i.e., cancer therapy
      related toxicities) may strongly affect quality of life.

PMID- 29473118
TI  - A Nanocrystalline Fe2O3 Film Anode Prepared by Pulsed Laser Deposition for
      Lithium-Ion Batteries.
AB  - Nanocrystalline Fe2O3 thin films are deposited directly on the conduct substrates
      by pulsed laser deposition as anode materials for lithium-ion batteries. We
      demonstrate the well-designed Fe2O3 film electrodes are capable of excellent high
      rate performance (510 mAh g- 1 at high current density of 15,000 mA g- 1) and
      superior cycling stability (905 mAh g- 1 at 100 mA g- 1 after 200 cycles), which
      are among the best reported state-of-the-art Fe2O3 anode materials. The
      outstanding lithium storage performances of the as-synthesized nanocrystalline
      Fe2O3 film are attributed to the advanced nanostructured architecture, which not
      only provides fast kinetics by the shortened lithium-ion diffusion lengths but
      also prolongs cycling life by preventing nanosized Fe2O3 particle agglomeration.
      The electrochemical performance results suggest that this novel Fe2O3 thin film
      is a promising anode material for all-solid-state thin film batteries.

PMID- 29473120
TI  - Analogies and disparities among scintigraphic bone tracers in the diagnosis of
      cardiac and non-cardiac ATTR amyloidosis.
AB  - In this issue of JNC, BW Spery and Coll report a retrospective analysis of 57
      patients with transthyretin-related amyloidosis (ATTR) in an advanced phase of
      the disease who underwent 99mTechnetium-pyrophosphate (99mTcPYP) scintigraphy.
      Although relatively small and "negative," the study is relevant since it broadens
      our knowledge on the uptake of "bone tracers" in ATTR and contributes to
      understand the limitations of the clinical use of scintigraphy in this disease.
      The paper raises, directly or indirectly, at least three questions: To what
      extent are the different bone tracers interchangeable for the diagnosis of ATTR
      cardiac amyloidosis? Are bone tracers able to image non-cardiac ATTR amyloidosis?
      What is the explanation for the variable performance of the different bone
      tracers in the diagnosis of cardiac and extracardiac ATTR amyloidosis?

PMID- 29473121
TI  - Pricing of HPV Vaccines in Europe: Back to the Future?

PMID- 29473119
TI  - Impact of age at diagnosis and duration of type 2 diabetes on mortality in
      Australia 1997-2011.
AB  - AIMS/HYPOTHESIS: Current evidence suggests that type 2 diabetes may have a
      greater impact on those with earlier diagnosis (longer duration of disease), but
      data are limited. We examined the effect of age at diagnosis of type 2 diabetes
      on the risk of all-cause and cause-specific mortality over 15 years. METHODS: The
      data of 743,709 Australians with type 2 diabetes who were registered on the
      National Diabetes Services Scheme (NDSS) between 1997 and 2011 were examined.
      Mortality data were derived by linking the NDSS to the National Death Index. All
      cause mortality and mortality due to cardiovascular disease (CVD), cancer and all
      other causes were identified. Poisson regression was used to model mortality
      rates by sex, current age, age at diagnosis, diabetes duration and calendar time.
      RESULTS: The median age at registration on the NDSS was 60.2 years (interquartile
      range [IQR] 50.9-69.5) and the median follow-up was 7.2 years (IQR 3.4-11.3). The
      median age at diagnosis was 58.6 years (IQR 49.4-67.9). A total of 115,363 deaths
      occurred during 7.20 million person-years of follow-up. During the first 1.8
      years after diabetes diagnosis, rates of all-cause and cancer mortality declined
      and CVD mortality was constant. All mortality rates increased exponentially with
      age. An earlier diagnosis of type 2 diabetes (longer duration of disease) was
      associated with a higher risk of all-cause mortality, primarily driven by CVD
      mortality. A 10 year earlier diagnosis (equivalent to 10 years' longer duration
      of diabetes) was associated with a 1.2-1.3 times increased risk of all-cause
      mortality and about 1.6 times increased risk of CVD mortality. The effects were
      similar in men and women. For mortality due to cancer (all cancers and colorectal
      and lung cancers), we found that earlier diagnosis of type 2 diabetes was
      associated with lower mortality compared with diagnosis at an older age.
      CONCLUSIONS/INTERPRETATION: Our findings suggest that younger-onset type 2
      diabetes increases mortality risk, and that this is mainly through earlier CVD
      mortality. Efforts to delay the onset of type 2 diabetes might, therefore, reduce
      mortality.

PMID- 29473122
TI  - Medicinal Cannabis and the Tyranny of Distance: Policy Reform Required for
      Optimizing Patient and Health System Net Benefit in Australia.

PMID- 29473124
TI  - Correction to: Effects of pegvisomant and somatostatin receptor ligands on
      incidence of vertebral fractures in patients with acromegaly.
AB  - The original version of the article contained an error in the results section of
      the Abstract. The vertebral fractures (VFs) odds ratio is incorrectly published
      as 61.0 and the correct value is 6.10.

PMID- 29473123
TI  - Prognostic Factors in the Era of Targeted Therapies in CLL.
AB  - PURPOSE OF REVIEW: Chronic lymphocytic leukemia is heterogeneous disease
      characterized by a variable clinical course that is greatly influenced by various
      patient and disease characteristics. Over the last two decades, advent of new
      diagnostic methodologies has led to the identification of several factors of
      prognostic and predictive relevance. Furthermore, recent advances in next
      generation sequencing techniques has identified recurrent novel mutations in
      NOTCH1, SF3B1, BIRC3, and ATM genes whose role as prognostic and predictive
      markers is currently being investigated. These biologic markers carry new
      prognostic information and their incorporation into prognostic scoring systems
      will likely lead to refined multi-parameter risk models. RECENT FINDINGS: While
      the prognostic impact of many of the most commonly used markers on clinical
      outcomes in patients treated with chemo-immunotherapy is well documented, it is
      important to review their predictive and prognostic role in the era of novel
      targeted therapies. This article will discuss the currently available information
      on the clinical relevance of prognostic markers in patients treated with novel
      targeted therapies.

PMID- 29473125
TI  - Sulforaphane Attenuated the Pro-Inflammatory State Induced by Hydrogen Peroxide
      in SH-SY5Y Cells Through the Nrf2/HO-1 Signaling Pathway.
AB  - Sulforaphane (SFN), an isothiocyanate obtained from cruciferous vegetables,
      exerts antioxidant, antiapoptotic, and antitumor activities in different cell
      types. Moreover, SFN has been viewed as an anti-inflammatory agent. Nonetheless,
      the mechanism underlying the ability of SFN in modulating the immune response in
      mammalian cells is not completely understood yet. Therefore, we investigated here
      whether and how SFN would be effective in preventing inflammation induced by a
      pro-oxidant agent (hydrogen peroxide, H2O2) in the human neuroblastoma SH-SY5Y
      cells. The cells were treated with SFN at 5 MUM for 30 min before a challenge
      with H2O2 for an additional 24 h. Pretreatment with SFN reduced the secretion of
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), as well
      as decreased the levels of cyclooxygenase-2 (COX-2) in H2O2-treated cells. SFN
      also decreased the activity of the transcription factor nuclear factor-kappaB (NF
      kappaB) and the immunocontent of the p65 NF-kappaB subunit in the cell nucleus.
      The inhibition of heme oxygenase-1 (HO-1) by ZnPP-IX at 10 MUM or the silencing
      of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor by
      small interfering RNA targeting Nrf2 attenuated the anti-inflammatory and
      cytoprotective effects induced by SFN. Therefore, SFN exerted an anti
      inflammatory effect in H2O2-challenged SH-SY5Y cells by a mechanism dependent on
      the Nrf2/HO-1 signaling pathway.

PMID- 29473126
TI  - An efficient data mining framework for the characterization of symptomatic and
      asymptomatic carotid plaque using bidimensional empirical mode decomposition
      technique.
AB  - Atherosclerosis is a type of cardiovascular disease which may cause stroke. It is
      due to the deposition of fatty plaque in the artery walls resulting in the
      reduction of elasticity gradually and hence restricting the blood flow to the
      heart. Hence, an early prediction of carotid plaque deposition is important, as
      it can save lives. This paper proposes a novel data mining framework for the
      assessment of atherosclerosis in its early stage using ultrasound images. In this
      work, we are using 1353 symptomatic and 420 asymptomatic carotid plaque
      ultrasound images. Our proposed method classifies the symptomatic and
      asymptomatic carotid plaques using bidimensional empirical mode decomposition
      (BEMD) and entropy features. The unbalanced data samples are compensated using
      adaptive synthetic sampling (ADASYN), and the developed method yielded a
      promising accuracy of 91.43%, sensitivity of 97.26%, and specificity of 83.22%
      using fourteen features. Hence, the proposed method can be used as an assisting
      tool during the regular screening of carotid arteries in hospitals. Graphical
      abstract Outline for our efficient data mining framework for the characterization
      of symptomatic and asymptomatic carotid plaques.

PMID- 29473127
TI  - Difference in the degree of improvement in patient-reported outcomes after total
      knee arthroplasty between octogenarians and sexagenarians: a propensity score
      matching analysis.
AB  - BACKGROUND: As the population ages, the use of primary total knee arthroplasty
      (TKA) is on the rise in the octogenarian population. AIMS: The objective of this
      study was to compare patient-reported outcomes after TKA in octogenarians versus
      sexagenarians. METHODS: This retrospective case-controlled comparative study with
      a propensity score matching analysis was conducted by 251 patients who underwent
      TKA for degenerative osteoarthritis of the knee. After the propensity score
      matching analysis, 38 octogenarians and 41 sexagenarians were identified. Range
      of motion (ROM), degree of flexion contracture, Charlson Comorbidity Index score,
      Knee Society score (KSS), Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) scores, the 36-Item Short-Form Health Survey (SF
      36), postoperative complications, length of stay, and 90-day mortality after TKA
      were compared. The degree of improvement of each functional parameter was also
      assessed. RESULTS: There was no significant difference in the degree of
      improvement in postoperative ROM, flexion contracture, or KSS. There were only
      significant differences in length of hospital stay and volume of blood
      transfusion (p < 0.001 and p = 0.004, respectively). The octogenarian patient
      group showed significantly inferior outcomes for WOMAC and SF-36 score compared
      to the sexagenarian patient group (p = 0.009 and p = 0.022, respectively).
      CONCLUSION: Although the functional improvements after TKA were excellent
      regardless of age, TKA seemed to contribute little to quality of life in
      octogenarian patients. Therefore, a careful approach to improving satisfaction
      with subjective outcomes is needed for octogenarian patients who undergo TKA.

PMID- 29473128
TI  - Landmark-based evaluation of a deformable motion correction for DCE-MRI of the
      liver.
AB  - PURPOSE: Annotation of meaningful landmark ground truth on DCE-MRI is difficult
      and laborious. Motion correction methods applied to DCE-MRI of the liver are thus
      mostly evaluated using qualitative or indirect measures. We propose a novel
      landmark annotation scheme that facilitates the generation of landmark ground
      truth on larger clinical datasets. METHODS: In our annotation scheme, landmarks
      are equally distributed over all time points of all available dataset cases and
      annotated by multiple observers on a per-pair basis. The scheme is used to
      annotate 26 DCE-MRI of the liver. A subset of the ground truth is used to
      optimize parameters of a deformable motion correction. Several variants of the
      motion correction are evaluated on the remaining cases with respect to distances
      of corresponding landmarks after registration, deformation field properties, and
      qualitative measures. RESULTS: A landmark ground truth on 26 cases could be
      generated in under 12 h per observer with a mean inter-observer distance below
      the mean voxel diagonal. Furthermore, the landmarks are spatially well
      distributed within the liver. Parameter optimization significantly improves the
      performance of the motion correction, and landmark distance after registration is
      2 mm. Qualitative evaluation of the motion correction reflects the quantitative
      results. CONCLUSIONS: The annotation scheme makes a landmark-based evaluation of
      motion corrections for hepatic DCE-MRI practically feasible for larger clinical
      datasets. The comparably large number of cases enables both optimization and
      evaluation of motion correction methods.

PMID- 29473129
TI  - Agile convolutional neural network for pulmonary nodule classification using CT
      images.
AB  - OBJECTIVE: To distinguish benign from malignant pulmonary nodules using CT images
      is critical for their precise diagnosis and treatment. A new Agile convolutional
      neural network (CNN) framework is proposed to conquer the challenges of a small
      scale medical image database and the small size of the nodules, and it improves
      the performance of pulmonary nodule classification using CT images. METHODS: A
      hybrid CNN of LeNet and AlexNet is constructed through combining the layer
      settings of LeNet and the parameter settings of AlexNet. A dataset with 743 CT
      image nodule samples is built up based on the 1018 CT scans of LIDC to train and
      evaluate the Agile CNN model. Through adjusting the parameters of the kernel
      size, learning rate, and other factors, the effect of these parameters on the
      performance of the CNN model is investigated, and an optimized setting of the CNN
      is obtained finally. RESULTS: After finely optimizing the settings of the CNN,
      the estimation accuracy and the area under the curve can reach 0.822 and 0.877,
      respectively. The accuracy of the CNN is significantly dependent on the kernel
      size, learning rate, training batch size, dropout, and weight initializations.
      The best performance is achieved when the kernel size is set to [Formula: see
      text], the learning rate is 0.005, the batch size is 32, and dropout and Gaussian
      initialization are used. CONCLUSIONS: This competitive performance demonstrates
      that our proposed CNN framework and the optimization strategy of the CNN
      parameters are suitable for pulmonary nodule classification characterized by
      small medical datasets and small targets. The classification model might help
      diagnose and treat pulmonary nodules effectively.

PMID- 29473130
TI  - Percutaneous endoscopic gastrostomy site infections-Incidence and risk factors.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) placement is the modality
      of choice for long-term enteral nutrition in view of technical ease and cost
      effectiveness. Peristomal infection (PI) remains the most common complication
      following PEG tube placement. The aim of this study was to assess the incidence
      and risk factors for PI and outline a microbiological profile that can aid in
      prophylactic and therapeutic strategies. METHODS: A retrospective study of 781
      patients who underwent PEG placement (Cook PEG-Pull-S-20Fr/24Fr) from 2010 to
      2015 at our tertiary care center were included. Relevant data were collected from
      the hospital electronic medical records. The incidence of PI was computed and
      potential risk factors were assessed using univariate analysis. The
      microbiological profile was created along with sensitivity patterns after
      reviewing the culture reports. Statistical analysis was performed using SPSS
      version 20.0. RESULTS: PEG tube placement was performed in 781 patients (mean age
      55.9 +/- 36.1; M:F = 2:75). The major indication was oropharyngeal malignancies.
      PI was seen in 171 patients (21.9%). Diabetes mellitus, duration of hospital stay
      more than 7 days, and hypoalbuminemia were found to be significant risk factors
      for the development of PI (p < 0.05). Patients who had chemotherapy or
      radiotherapy before PEG placement had a higher incidence of peristomal infections
      (p 0.00). Pseudomonas and Klebsiella were the most common organisms causing
      infection. CONCLUSIONS: PI remains a significant complication of PEG placement.
      Pseudomonas and Klebsiella are the most common organisms and prophylactic
      antibiotic protocols should be tailored accordingly. Elective PEG before the
      institution of chemotherapy/radiotherapy in patients with oropharyngeal
      malignancies is recommended.

PMID- 29473131
TI  - Searching for new drugs for Chagas diseases: triazole analogs display high in
      vitro activity against Trypanosoma cruzi and low toxicity toward mammalian cells.
AB  - Chagas disease is one of the most relevant endemic diseases in Latin America
      caused by the flagellate protozoan Trypanosoma cruzi. Nifurtimox and
      benzonidazole are the drugs used in the treatment of this disease, but they
      commonly are toxic and present severe side effects. New effective molecules,
      without collateral effects, has promoted the investigation to develop new lead
      compounds with to advance for clinical trials. Previously, 3-nitro-1H-1,2,4
      triazole-based amines and 1,2,3-triazoles demonstrated significant trypanocidal
      activity against T. cruzi. In this paper, we synthesized a new series of 92
      examples of 1,2,3-triazoles. Six compounds exhibited antiparasitic activity, 14,
      25, 27, 31 and 40, 43 and were effective against epimastigotes of two strains of
      T. cruzi (Y and Dm28-C) and 25, 27 and 31 exhibited trypanocidal activity similar
      to benzonidazole. Notably, the compound 25 compared to benzonidazole increase the
      toxicity against T. cruzi, with no apparent toxicity to the cell line of mice
      macrophages or primary mice peritoneal macrophages. As results, we calculated
      selectivity indexes up to 2000 to 25 and 31 in both T. cruzi strains. Derivative
      14 caused a trypanostatic effect because it did not damage external epimastigote
      membrane. Triazoles 40 and 43 impaired parasites viability using a pathway not
      dependent on ROS production.

PMID- 29473132
TI  - Error-prone PCR mutagenesis and reverse bacterial two-hybrid screening identify a
      mutation in asparagine 53 of the Staphylococcus aureus ESAT6-like component EsxB
      that perturbs interaction with EsxD.
AB  - The ESAT6-like Secretion System (ESS) of the human pathogen Staphylococcus aureus
      secretes heterodimeric virulence effectors such as EsxB and EsxD. To gain
      insights into the nature of EsxB-EsxD interaction, randomly mutated esxB
      generated by error-prone PCR was co-transformed together with esxD as adenylate
      cyclase fusion constructs into cyclase-deficient Escherichia coli, followed by
      reverse bacterial two-hybrid screening. Three color species were observed: dark
      blue, light blue, and white (no EsxB-EsxD interaction). The esxB from white
      colonies was subjected to standard PCR to check for gene signal, followed by SDS
      PAGE for variant stability assessment. The gene coding for a stable EsxB variant
      that perturbed interaction with EsxD was further subjected to DNA sequencing. A
      single point mutation in esxB at position 157 was identified, leading to an amino
      acid change from asparagine to aspartic acid at position 53 in the resulting
      protein. Structural modeling of EsxB reveals that N53 is surface exposed. Whereas
      N53S substitution by site-directed mutagenesis retained heterodimerization with
      EsxD, N53A substitution abrogated such interaction. In addition, N53D change in
      EsxB did not alter interaction with EssG, another soluble component of the ESS
      pathway, suggesting minimal impact of the N53D substitution on EsxB stability and
      solubility. Taken together, these data provide new insights into the nature of
      EsxB-EsxD interaction and offer a systematic approach for in vivo analysis of
      protein-protein interactions of pathogenic bacteria in non-pathogenic hosts.

PMID- 29473133
TI  - Self-Assessment of Teaching Skills Among Psychiatric Residents.
AB  - OBJECTIVE: Psychiatry residency programs have increasingly emphasized the role of
      resident-as-teacher; however, little is known about resident self-perceptions of
      teaching skills. This study reports on psychiatry residents' self-perceived
      skills in teaching medical students and compares cohort ratings with anonymous
      medical student evaluations of residents as teachers at our large academic
      residency program. METHODS: In May-June 2016, 84 residents in our program were
      surveyed using an anonymous, web-based survey, and this data was then compared to
      3 years of aggregate data from anonymous student evaluations of resident teaching
      at our institution. RESULTS: Forty-seven (47) residents responded to the survey
      (56% response rate). Residents reported self-perceived deficits in several
      specific teaching competencies. Medical students consistently rated residents
      higher with respect to teaching skills than residents rated themselves, and these
      data were highly statistically significant. CONCLUSION: This study underscores
      the benefits of resident self-assessment in comparison to medical student
      evaluations of residents as teachers and this information can be used to inform
      training programs' resident-as-teacher curricula.

PMID- 29473134
TI  - Developing a Digitally Informed Curriculum in Psychiatry Education and Clinical
      Practice.

PMID- 29473136
TI  - Factors that Influence Parental Misperception of Their Child's Actual Weight
      Status in South Carolina.
AB  - Objectives Studies suggest that parents tend to misperceive their child's actual
      weight status and typically underestimate their child's weight. Since few studies
      examine the factors that influence parental misperception, this study aims to
      assess the influence of parent and child factors with parental misperception of
      their child's actual weight status who were either at their recommended weight or
      overweight/obese in South Carolina in 2013 and 2014. Methods Secondary data were
      obtained from the Behavioral Risk Factor Surveillance System (BRFSS) and the
      Children's Health Assessment Survey (CHAS) in 2013 and 2014 in SC. Parental
      misperception of child's actual weight status was measured by comparing parental
      perception to their child's actual weightstatus measured via BMI. Logistic
      regression was conducted to assess the association between parental and child
      factors with parental misperception of child's weight status. Results In the
      adjusted multivariate analysis, only child's age was significantly and positively
      associated with parental misperception of their child's actual weight status.
      Conclusions for Practice This cross sectional analysis showed an association
      between child's age and parental misperception of child's actual weight status.
      It is essential to educate parents about their children's weight status,
      especially among young children.

PMID- 29473135
TI  - Immunomodulatory Effects of CP-25 on Splenic T Cells of Rats with Adjuvant
      Arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease in which T cells play an
      important role. Paeoniflorin-6-oxy-benzenesulfonate (CP-25) shows a strong anti
      inflammatory and immunomodulatory effect in the joint of adjuvant arthritis (AA)
      rats, but the role of the spleen function is still unclear. The aim of this study
      was to research how CP-25 regulated spleen function of AA rats. Male Sprague
      Dawley rats were administered with CP-25 (50 mg/kg) orally from day 17 to 29
      after immunization. The spleen histopathological changes were analyzed by
      hematoxylin-eosin staining. G protein-coupled receptor kinases (GRKs) and
      prostaglandin receptor subtypes (EPs) were screened by Western blot and
      immunohistochemistry. The co-expression of GRK2 and EP2 as well as GRK2 and EP4
      was measured by immunofluorescence and co-immunoprecipitation. The expression of
      GRK2 and EP4 in splenic T cells was further detected by immunofluorescence. CP-25
      was found to relieve the secondary paw swelling, attenuate histopathologic
      changes, and downregulate GRK2, EP2 and EP4 expression in AA rats. Additionally,
      CP-25 not only downregulated the co-expression of GRK2 and EP4 but also
      downregulated GRK2, EP4 expression in splenic T cells of AA rats. From these
      results, we can infer that CP-25 play an anti-inflammatory and immune function by
      affecting the function of the splenic T cells.

PMID- 29473137
TI  - Assessing associations between indoor environment and health symptoms in Romanian
      school children: an analysis of data from the SINPHONIE project.
AB  - School environment may have an impact on children's health, but few studies have
      focused on indoor comfort factors such as temperature, humidity, and noise in
      relation with potential effects on children's health. Our cross-sectional study
      used data from the European Schools Indoor Pollution and Health Observatory
      Network in Europe (SINPHONIE) project to assess children's allergy, asthma-like
      symptoms, and flu-like symptoms in relation with classroom comfort and
      environmental factors. The study used self-reported data from three
      questionnaires to identify classroom conditions and student health outcomes for
      280 students. We used backwards variable selection and unconditional logistic
      regression to assess the outcome-environment relationship while controlling for
      demographics, family history of allergy, and home exposures. We found increased
      risks for allergy and flu-like symptoms associated with hot classrooms in the
      heating season, increased risks for asthma-like symptoms associated with noisy
      classrooms, and a protective effect for allergy associated with good outdoor air
      quality. Romanian classrooms rely on natural ventilation, which may contribute to
      increased temperature and humidity in the heating season. Further research
      warrants the use of SINPHONIE's measurement data to validate our findings.

PMID- 29473138
TI  - Family environmental and dietary implications for low-level prenatal lead
      exposure in Wujiang City, China.
AB  - To explore the potential environmental and dietary factors during pregnancy
      affecting low-level prenatal lead exposure, we conducted a longitudinal study in
      Wujiang City, China. A total of 1976 mother-infant pairs were included from 2009
      to 2010. An interviewed questionnaire was conducted and cord blood samples were
      collected. The geometric means of cord blood lead level was 30.3 MUg/L (95% CI,
      29.8-30.8) with 99.24% below 100 MUg/L. Maternal age, passive smoking, and living
      in the countryside were significantly associated with cord blood lead
      concentrations. Multiple logistic models showed that some family environmental
      factors including using firewood and electricity as kitchen fuel were positively
      correlated with increased cord blood lead levels. Among dietary sources recorded
      in this study, meat consumption (> 3 times/week), fish consumption (1-3
      times/week), vegetables consumption (> 1 times/day), and fruit intake (> 1
      times/day) had inverse relationship with cord blood lead levels. In general, our
      findings may have important implications for family environmental and dietary
      direction during pregnancy to decrease prenatal lead exposure.

PMID- 29473140
TI  - Variance of the global signal as a pretreatment predictor of antidepressant
      treatment response in drug-naive major depressive disorder.
AB  - Several behavioral and neuroimaging markers could be used to predict eventual
      antidepressant medication (ADM) outcomes in patients with major depressive
      disorder (MDD). However, these predictors are either subjective or complex, which
      has limited their clinical use. Thus, we aimed to identify an objective and easy
      to-get marker to predict early therapeutic efficacy. Forty-seven drug-naive
      patients with MDD and 47 age-, gender- and education-matched healthy controls
      underwent resting-state functional magnetic resonance imaging (fMRI) scans. We
      calculated the variable coefficient (VC) of the global signal for each subject.
      Baseline Hamilton Rating Scale for Depression (HRSD) score and that after 2 weeks
      of ADM were assessed for patients. Although there was no difference in VC between
      patients with MDD and healthy controls, we found a significant positive
      correlation between the VC and the decline rate of HRSD scores in the patients.
      Compared with the non-responding depression (NRD) group, the treatment-responsive
      depression (TRD) group had a higher VC. Receiver operator characteristic curve
      analysis revealed that the VC exhibited a good ability to differentiate TRD from
      NRD. In addition, the linear and logistic regression analyses showed that the VC
      was a significant predictor of the decline rate of HRSD scores and the
      antidepressant treatment response. These findings suggest that variance of the
      global signal may serve as a useful marker to help clinicians find an appropriate
      drug for individuals with MDD at the earliest opportunity and then further to
      facilitate personalized therapy.

PMID- 29473139
TI  - Effects of soil pyrene contamination on growth and phenolics in Norway spruce
      (Picea abies) are modified by elevated temperature and CO2.
AB  - With the constant accumulation of polycyclic aromatic hydrocarbons (PAHs) in soil
      and increasing temperature and CO2 levels, plants will inevitably be exposed to
      combined stress. Studies on the effects of such combined stresses are needed to
      develop mitigation and adaptation measures. Here, we investigated the effects of
      soil pyrene contamination (50 mg kg-1) on growth and phenolics of 1-year-old
      Norway spruce seedlings from five different origins in Finland at elevated
      temperature (+ 2  degrees C) and CO2 (+ 360 ppm). Pyrene significantly decreased
      spruce height growth (0-48%), needle biomass (0-44%), stem biomass (0-43%), and
      total phenolic concentrations in needles (2-13%) and stems (1-19%) compared to
      control plants. Elevated temperature alone did not affect growth but led to lower
      concentrations of total phenolics in needles (5-29%) and stems (5-18%) in both
      soil treatments. By contrast, elevated CO2 led to higher needle biomass (0-39%)
      in pyrene-spiked soils and higher concentrations of stem phenolics (0-18%) in
      pyrene-spiked and control soils compared to ambient treatments. The decrease in
      height growth and phenolic concentrations caused by pyrene was greater at
      elevated temperature, while elevated CO2 only marginally modified the response.
      Seedlings from different origins showed different responses to the combined
      environmental stressors. The changes in growth and in the quantity and quality of
      phenolics in this study suggest that future climate changes will aggravate the
      negative influence of soil pyrene pollution on northern conifer forest
      ecosystems.

PMID- 29473142
TI  - Visually induced gains in pitch discrimination: Linking audio-visual processing
      with auditory abilities.
AB  - Perception is fundamentally a multisensory experience. The principle of inverse
      effectiveness (PoIE) states how the multisensory gain is maximal when responses
      to the unisensory constituents of the stimuli are weak. It is one of the basic
      principles underlying multisensory processing of spatiotemporally corresponding
      crossmodal stimuli that are well established at behavioral as well as neural
      levels. It is not yet clear, however, how modality-specific stimulus features
      influence discrimination of subtle changes in a crossmodally corresponding
      feature belonging to another modality. Here, we tested the hypothesis that
      reliance on visual cues to pitch discrimination follow the PoIE at the
      interindividual level (i.e., varies with varying levels of auditory-only pitch
      discrimination abilities). Using an oddball pitch discrimination task, we
      measured the effect of varying visually perceived vertical position in
      participants exhibiting a wide range of pitch discrimination abilities (i.e.,
      musicians and nonmusicians). Visual cues significantly enhanced pitch
      discrimination as measured by the sensitivity index d', and more so in the
      crossmodally congruent than incongruent condition. The magnitude of gain caused
      by compatible visual cues was associated with individual pitch discrimination
      thresholds, as predicted by the PoIE. This was not the case for the magnitude of
      the congruence effect, which was unrelated to individual pitch discrimination
      thresholds, indicating that the pitch-height association is robust to variations
      in auditory skills. Our findings shed light on individual differences in
      multisensory processing by suggesting that relevant multisensory information that
      crucially aids some perceivers' performance may be of less importance to others,
      depending on their unisensory abilities.

PMID- 29473141
TI  - The Trypanosoma cruzi RNA-binding protein RBP42 is expressed in the cytoplasm
      throughout the life cycle of the parasite.
AB  - Trypanosoma cruzi, the protozoan parasite that causes Chagas disease in humans,
      has a complex life cycle that promotes survival in disparate environments. In
      each environment, the parasite must fine-tune its metabolic pathways to divide
      and multiply. In the absence of recognizable transcriptional gene regulation, it
      is apparent that protein levels are determined by post-transcriptional
      mechanisms. Post-transcriptional gene control is influenced by RNA-binding
      proteins that target mRNAs in the cell's cytoplasm. To initiate the study of post
      transcriptional activities in T. cruzi, we studied this organism's ortholog of
      RBP42, a trypanosomal RNA-binding protein. RBP42 was originally detected in
      Trypanosoma brucei and was shown to target a subset of mRNAs that encode proteins
      governing central carbon metabolism. T. cruzi RBP42 structurally resembles T.
      brucei RBP42, sharing an NTF2 domain at its amino terminus and a single RNA
      binding domain (specifically, the RNA recognition motif, or RRM), at its carboxy
      terminus. A phylogenetic analysis reveals that an NTF2 and a single RRM are
      distinguishing features of all RBP42 orthologs within the broad kinetoplastid
      grouping. T. cruzi RBP42 is expressed in all life cycle stages of the parasite as
      determined by immunoblot and immunofluorescence microscopy. In each case, the
      protein is localized to the cytoplasm, indicating a role for T. cruzi RBP42 in
      post-transcriptional activities in all stages of the parasite life cycle. We
      speculate that RBP42 influences the dynamic metabolic pathways responsible for
      parasite infection and transmission.

PMID- 29473143
TI  - Emotionally conditioning the target-speech voice enhances recognition of the
      target speech under "cocktail-party" listening conditions.
AB  - Under a noisy "cocktail-party" listening condition with multiple people talking,
      listeners can use various perceptual/cognitive unmasking cues to improve
      recognition of the target speech against informational speech-on-speech masking.
      One potential unmasking cue is the emotion expressed in a speech voice, by means
      of certain acoustical features. However, it was unclear whether emotionally
      conditioning a target-speech voice that has none of the typical acoustical
      features of emotions (i.e., an emotionally neutral voice) can be used by
      listeners for enhancing target-speech recognition under speech-on-speech masking
      conditions. In this study we examined the recognition of target speech against a
      two-talker speech masker both before and after the emotionally neutral target
      voice was paired with a loud female screaming sound that has a marked negative
      emotional valence. The results showed that recognition of the target speech
      (especially the first keyword in a target sentence) was significantly improved by
      emotionally conditioning the target speaker's voice. Moreover, the emotional
      unmasking effect was independent of the unmasking effect of the perceived spatial
      separation between the target speech and the masker. Also, (skin conductance)
      electrodermal responses became stronger after emotional learning when the target
      speech and masker were perceptually co-located, suggesting an increase of
      listening efforts when the target speech was informationally masked. These
      results indicate that emotionally conditioning the target speaker's voice does
      not change the acoustical parameters of the target-speech stimuli, but the
      emotionally conditioned vocal features can be used as cues for unmasking target
      speech.

PMID- 29473145
TI  - Considerations for Developing Targeted Therapies in Low-Frequency Molecular
      Subsets of a Disease.
AB  - Advances in our understanding of the molecular underpinnings of disease have
      spurred the development of targeted therapies and the use of precision medicine
      approaches in patient care. While targeted therapies have improved our capability
      to provide effective treatments to patients, they also present additional
      challenges to drug development and benefit-risk assessment such as identifying
      the subset(s) of patients likely to respond to the drug, assessing heterogeneity
      in response across molecular subsets of a disease, and developing diagnostic
      tests to identify patients for treatment. These challenges are particularly
      difficult to address when targeted therapies are developed to treat diseases with
      multiple molecular subtypes that occur at low frequencies. To help address these
      challenges, the US Food and Drug Administration recently published a draft
      guidance entitled "Developing Targeted Therapies in Low-Frequency Molecular
      Subsets of a Disease." Here we provide additional information on specific aspects
      of targeted therapy development in diseases with low-frequency molecular subsets.

PMID- 29473144
TI  - Speaker information affects false recognition of unstudied lexical-semantic
      associates.
AB  - Recognition of and memory for a spoken word can be facilitated by a prior
      presentation of that word spoken by the same talker. However, it is less clear
      whether this speaker congruency advantage generalizes to facilitate recognition
      of unheard related words. The present investigation employed a false memory
      paradigm to examine whether information about a speaker's identity in items heard
      by listeners could influence the recognition of novel items (critical intruders)
      phonologically or semantically related to the studied items. In Experiment 1,
      false recognition of semantically associated critical intruders was sensitive to
      speaker information, though only when subjects attended to talker identity during
      encoding. Results from Experiment 2 also provide some evidence that talker
      information affects the false recognition of critical intruders. Taken together,
      the present findings indicate that indexical information is able to contact the
      lexical-semantic network to affect the processing of unheard words.

PMID- 29473146
TI  - Perceptual experience shapes our ability to categorize faces by national origin:
      A new other-race effect.
AB  - People are better at recognizing own-race than other-race faces. This other-race
      effect has been argued to be the result of perceptual expertise, whereby face
      specific perceptual mechanisms are tuned through experience. We designed new
      tasks to determine whether other-race effects extend to categorizing faces by
      national origin. We began by selecting sets of face stimuli for these tasks that
      are typical in appearance for each of six nations (three Caucasian, three Asian)
      according to people from those nations (Study 1). Caucasian and Asian
      participants then categorized these faces by national origin (Study 2). Own-race
      faces were categorized more accurately than other-race faces. In contrast, Asian
      American participants, with more extensive other-race experience than the first
      Asian group, categorized other-race faces better than own-race faces,
      demonstrating a reversal of the other-race effect. Therefore, other-race effects
      extend to the ability to categorize faces by national origin, but only if
      participants have greater perceptual experience with own-race, than other-race
      faces. Study 3 ruled out non-perceptual accounts by showing that Caucasian and
      Asian faces were sorted more accurately by own-race than other-race participants,
      even in a sorting task without any explicit labelling required. Together, our
      results demonstrate a new other-race effect in sensitivity to national origin of
      faces that is linked to perceptual expertise.

PMID- 29473147
TI  - Agency and responsibility in adolescent students: A challenge for the societies
      of tomorrow.
AB  - BACKGROUND: The literature in educational psychology converges on the idea that
      students should take an active and accountable position in their learning
      processes. Nevertheless, there is still a lack of research that has
      systematically put the constructs of agency and responsibility at the core of
      their interests. AIMS: In this study, we explore whether good experiences at
      school - here conceptualized as the general level of basic needs fulfilment and
      interpersonal justice - impact on student agency and responsibility, which in
      turn are considered as possible mediators between a good educational experience
      and two outcome measures, that is, academic achievement and career decision
      making self-efficacy. PARTICIPANTS: The study was held on a sample of 911 high
      school students equally distributed between males and females. METHOD: Data were
      collected through the use of a questionnaire comprising six measures assessing
      students' basic psychological need fulfilment, interpersonal justice, agentic
      engagement, responsibility for learning, academic achievement, and career
      decision-making self-efficacy. RESULTS AND CONCLUSIONS: Structural equation
      modelling indicated that basic needs fulfilment positively predicts agency,
      responsibility, academic achievement, and career decision-making self-efficacy.
      Interpersonal justice positively predicts responsibility. The indirect effect
      from basic psychological needs on career decision-making self-efficacy through
      the mediating effects of student agentic engagement and student responsibility
      was significant. The indirect effect from interpersonal justice on career
      decision-making self-efficacy through the mediating effect of student
      responsibility for learning was significant. These results are commented at the
      light of their implications for teacher practices, as they emphasize the
      importance of good experiences at school for promoting in students an active
      civic sense and a greater accountability.

PMID- 29473148
TI  - A subset of patients with pemphigoid (herpes) gestationis has serological
      evidence of celiac disease.
AB  - BACKGROUND: Pemphigoid (herpes) gestationis (PG) is an uncommon, self-limited
      disease with other autoimmune associations; however, celiac disease (CD) is not
      recognized as one. METHODS: From 71 patients' sera submitted for herpes
      gestationis factor (HGF) testing over a 5-year period, 12 were consistent with PG
      demonstrating HGF and increased IgG BP180 antibody levels; these sera were tested
      for IgA and IgG endomysial antibodies (EMA), epithelial basement membrane zone
      and cell surface antibodies by indirect immunofluorescence, and for IgA and IgG
      tissue transglutaminase (transglutaminase 2 or TG2) antibodies, IgA epidermal
      transglutaminase (transglutaminase 3 or TG3) antibodies, IgG BP230, and IgG
      desmoglein 1 and desmoglein 3 antibodies by enzyme-linked immunosorbent assays
      (ELISAs). RESULTS: Three of 12 patients' sera with PG (25%) had CD antibodies
      with positive IgA EMA and increased IgA TG2 antibody levels; two of these had
      positive IgG EMA, and one other had an increased IgA TG3 antibody level.
      CONCLUSIONS: A subset of patients with serological findings of PG also has
      serological evidence of CD, which may have implications in the etiopathogenesis
      of PG and which reveals important information about the mother's, and possibly
      her infant's, health.

PMID- 29473149
TI  - CYP2D6 and Endoxifen in Tamoxifen Therapy: A Tribute to David A. Flockhart.
AB  - This issue of Clinical Pharmacology & Therapeutics (CPT) includes the Clinical
      Pharmacogenetics Implementation Consortium (CPIC) guideline for using CYP2D6
      genotyping to guide tamoxifen therapy for breast cancer patients. CYP2D6
      metabolizes tamoxifen to its more active metabolite, endoxifen, and patients with
      reduced CYP2D6 activity have reduced circulating endoxifen concentrations. In
      this associated commentary, we recognize and honor the late Dr. David Flockhart,
      who began the research and made early fundamental discoveries on tamoxifen that
      have now resulted in this guideline.

PMID- 29473151
TI  - Couples' Perceptions of Each Other's Daily Affect: Empathic Accuracy, Assumed
      Similarity, and Indirect Accuracy.
AB  - This study examined couples' perceptions of each other's daily affect, using a
      daily diary methodology. Specifically, we tested the extent to which couples
      accurately inferred how their partner was feeling (empathic accuracy) and the
      extent to which spouses used their own feelings as a gauge for how their partner
      was feeling (assumed similarity). We also tested for indirect accuracy in
      couples' perceptions; that is, that assumed similarity in the context of actual
      similarity leads to empathic accuracy. Participants were 51 couples who completed
      daily diaries for seven consecutive nights. Results based on the Actor-Partner
      Interdependence Model indicated that couples showed both empathic accuracy and
      assumed similarity in their perception of their partner's positive affect;
      however, they used assumed similarity in rating their partner's hard negative
      (anger, hostility) and soft negative (sadness, fear) affect. Furthermore, tests
      of indirect accuracy found that wives were indirectly accurate in perceiving
      their husbands' positive affect and both husbands and wives were indirectly
      accurate in perceiving each other's hard negative affect because they were
      biased. Complementing laboratory studies, the present study highlights that
      examining couples' perceptions of each other's feelings in contexts of daily
      life, and differentiating positive and negative emotions, can further our
      understanding of the role of emotions for healthy relationship functioning.

PMID- 29473150
TI  - Better outcomes of modified myeloablative conditioning without antithymocyte
      globulin versus myeloablative conditioning in cord blood transplantation for
      hematological malignancies: A retrospective (development) and a prospective
      (validation) study.
AB  - Cord blood transplantation (CBT) is an effective option for treating
      hematological malignancies, but graft failure (GF) remains the primary cause of
      therapy failure. Thus, based on myeloablative conditioning (MAC) of busulfan with
      cyclophosphamide (Bu/Cy) or total body irradiation with Cy (TBI/Cy), fludarabine
      (Flu) was added to Bu/Cy and cytarabine (CA) to TBI/Cy for a modified
      myeloablative conditioning (MMAC). To compare the prognosis of MMAC with MAC, we
      conducted a retrospective study including 58 patients who underwent CBT with MAC
      or MMAC from 2000 to 2011. Neutrophil and platelet engraftment rate, overall
      survival (OS) and disease free survival (DFS) were significantly higher in the
      MMAC group (adjusted hazard ratio [HR], 2.58, 2.43, 0.36 and 0.37; p < 0.01, p =
      0.01, p = 0.02 and p = 0.02, separately). Nonrelapse mortality (NRM) was
      comparable (p = 0.183). To validate the outcomes noted in the MMAC group, we
      conducted a prospective single-arm clinical trial including 188 patients who
      underwent CBT with MMAC from 2011 to 2015. Engraftment rate, survival and NRM of
      the MMAC group in the prospective trail (MMAC-P) were similar to the MMAC group
      in the retrospective study (MMAC-R). This study is the first to demonstrate the
      superiority of MMAC to MAC in CBT for hematological malignancies.

PMID- 29473152
TI  - White matter spongiosis with vigabatrin therapy for infantile spasms.
AB  - The histopathology, "white matter spongiosis," defined by electron microscopy
      (EM) as "intramyelinic edema," has been associated with vigabatrin therapy in
      various animal models, but its role or significance in clinical studies is
      unknown. We conducted a neuropathological examination on a 27-month-old boy with
      bilateral polymicrogyria and epilepsy after sudden unexpected death in epilepsy
      (SUDEP). The patient was initiated on vigabatrin at 4 months of age, which
      controlled infantile spasms, and was continued as maintenance therapy. Autopsy
      showed a combination of developmental and acquired lesions: (1) bilateral gyral
      malformations of the frontal, parietal, temporal, and insular cortex; (2)
      agenesis of the olfactory tracts and bulbs; (3) hippocampal abnormalities:
      dentate gyrus bilamination and granule cell dispersion; and (4) areas of
      microscopic bilateral, symmetric white matter spongiosis in the brainstem central
      tegmental tract, amiculum and hilum of the inferior olive, medial longitudinal
      fasciculus, paragigantocellularis lateralis, optic nerves and chiasm, and
      hypothalamus. The white matter spongiosis was identical to the histopathologic
      lesions (which by EM exhibited intramyelinic edema) that were demonstrated in
      animal models on vigabatrin therapy, indicating that vigabatrin toxicity is not
      restricted to animal models.

PMID- 29473154
TI  - Polyunsaturated fatty acids and risk of melanoma: A Mendelian randomisation
      analysis.
AB  - Melanoma is the deadliest form of skin cancer, mainly affecting populations of
      European ancestry. Some observational studies suggest that particular diets
      reduce melanoma risk, putatively through an increase in polyunsaturated fatty
      acid (PUFA) consumption. However, interpretation of these observational findings
      is difficult due to residual confounding or reverse causality. To date, a
      randomized controlled trial has not been carried out to examine the relationship
      between PUFAs and melanoma. Hence, we performed a Mendelian randomisation (MR)
      study to evaluate the link between PUFAs and melanoma. To perform MR, we used
      summary results from the largest risk genome-wide association study (GWAS) meta
      analysis of melanoma, consisting of 12,874 cases and 23,203 controls. As
      instrumental variables we selected SNPs associated with PUFA levels from a GWAS
      meta-analysis of PUFA levels, from the CHARGE consortium. We used the inverse
      variance weighted method to estimate a causal odds ratio. To aid interpretation,
      we established a benchmark "large" predicted change in PUFAs in which, for
      example, an increase in docosahexaenoic acid (DPA) of 0.17 units (equal to 1
      standard deviation) moves a person from the 17th percentile to the median.
      Raising PUFA levels by a large amount (increasing DPA by 0.17 units) only
      negligibly changed melanoma risk: odds ratio [OR] = 1.03 (95% confidence interval
      [CI] = 0.96-1.10). Other PUFAs yielded similar results as DPA. Our MR analysis
      suggests that the effect of PUFA levels on melanoma risk is either zero or very
      small.

PMID- 29473153
TI  - Serum insulin-like growth factor (IGF)-I and IGF binding protein-3 in relation to
      terminal duct lobular unit involution of the normal breast in Caucasian and
      African American women: The Susan G. Komen Tissue Bank.
AB  - Lesser degrees of terminal duct lobular unit (TDLU) involution, as reflected by
      higher numbers of TDLUs and acini/TDLU, are associated with elevated breast
      cancer risk. In rodent models, the insulin-like growth factor (IGF) system
      regulates involution of the mammary gland. We examined associations of
      circulating IGF measures with TDLU involution in normal breast tissues among
      women without precancerous lesions. Among 715 Caucasian and 283 African American
      (AA) women who donated normal breast tissue samples to the Komen Tissue Bank
      between 2009 and 2012 (75% premenopausal), serum concentrations of IGF-I and
      binding protein (IGFBP)-3 were quantified using enzyme-linked immunosorbent
      assay. Hematoxilyn and eosin-stained tissue sections were assessed for numbers of
      TDLUs ("TDLU count"). Zero-inflated Poisson regression models with a robust
      variance estimator were used to estimate relative risks (RRs) for association of
      IGF measures (tertiles) with TDLU count by race and menopausal status, adjusting
      for potential confounders. AA (vs. Caucasian) women had higher age-adjusted mean
      levels of serum IGF-I (137 vs. 131 ng/mL, p = 0.07) and lower levels of IGFBP-3
      (4165 vs. 4684 ng/mL, p < 0.0001). Postmenopausal IGFBP-3 was inversely
      associated with TDLU count among AA (RRT3vs.T1  = 0.49, 95% CI = 0.28-0.84, p
      trend = 0.04) and Caucasian (RRT3vs.T1 =0.64, 95% CI = 0.42-0.98, p-trend = 0.04)
      women. In premenopausal women, higher IGF-I:IGFBP-3 ratios were associated with
      higher TDLU count in Caucasian (RRT3vs.T1 =1.33, 95% CI = 1.02-1.75, p-trend =
      0.04), but not in AA (RRT3vs.T1 =0.65, 95% CI = 0.42-1.00, p-trend = 0.05),
      women. Our data suggest a role of the IGF system, particularly IGFBP-3, in TDLU
      involution of the normal breast, a breast cancer risk factor, among Caucasian and
      AA women.

PMID- 29473155
TI  - Stiripentol efficacy and safety in Dravet syndrome: a 12-year observational
      study.
AB  - AIM: To assess long-term safety and efficacy of stiripentol as an antiepileptic
      medication for people with Dravet syndrome. METHOD: A prospective, observational
      open-label study (2003-2015) of the efficacy and long-term safety of stiripentol
      in patients with Dravet syndrome and ongoing seizures. Frequency of generalized
      tonic-clonic seizures, focal seizures, status epilepticus, and adverse events
      were recorded. RESULTS: Forty-one patients started stiripentol, with median age
      at enrolment 5 years 7 months (range 11mo-22y) and median duration of treatment
      37 months (range 2-141mo). Twenty out of 41 patients had greater than or equal to
      50% long-term reduction in frequency of generalized tonic-clonic seizures.
      Frequency of focal seizures was decreased by greater than or equal to 50% in 11
      out of 23 patients over the long-term. Frequency of status epilepticus was
      decreased by 50% or more in 11 out of 26 patients. The most common adverse events
      were anorexia, weight loss, sedation, and behavioural changes. One patient had
      worsening of absence and myoclonic seizures. Another developed recurrent
      pancreatitis on concurrent valproate. INTERPRETATION: Stiripentol improves long
      term seizure frequency in approximately 50% of patients with Dravet syndrome,
      when used as part of unrestricted polytherapy. Long-term use appears safe. In
      more than 40% of patients, episodes of status epilepticus markedly decrease after
      stiripentol initiation. What this paper adds Frequency of status epilepticus is
      reduced in 40% of patients with Dravet syndrome after stiripentol initiation.
      Stiripentol is effective for generalized tonic-clonic and focal seizures.
      Stiripentol can be safely used with a range of antiepileptic drugs.

PMID- 29473156
TI  - New Evidence on Employment Effects of Informal Care Provision in Europe.
AB  - OBJECTIVE: To estimate how labor force participation is affected when adult
      children provide informal care to their parents. DATA SOURCE: Survey of Health,
      Ageing and Retirement in Europe from 2004 to 2013. STUDY DESIGN: To offset the
      problem of endogeneity, we exploit the availability of other potential caregivers
      within the family as predictors of the probability to provide care for a
      dependent parent. Contrary to most previous studies, the dataset covers the whole
      working-age population in the majority of European countries. Individuals
      explicitly had to opt for or against the provision of care to their care
      dependent parents, which allows us to more precisely estimate the effect of
      caregiving on labor force participation. PRINCIPAL FINDINGS: Results reveal a
      negative causal effect that indicates that informal care provision reduces labor
      force participation by 14.0 percentage points (95 percent CI: -0.307, 0.026).
      Point estimates suggest that the effect is larger for men; however, this gender
      difference is not significantly different from zero at conventional levels.
      CONCLUSIONS: Results apply to individuals whose consideration in long-term care
      policy is highly relevant, that is, children whose willingness to provide
      informal care to their parents is altered by available alternatives of family
      caregivers.

PMID- 29473157
TI  - Nodule of Achilles tendon in a patient with kidney transplant revealing
      phaeohyphomycosis.

PMID- 29473158
TI  - Health-related quality of life in children with cerebral palsy in low- and middle
      income countries: opportunities and next steps.

PMID- 29473159
TI  - Developmental and degenerative cardiac defects in the Taiwanese mouse model of
      severe spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA), an autosomal recessive disease caused by a
      decrease in levels of the survival motor neuron (SMN) protein, is the most common
      genetic cause of infant mortality. Although neuromuscular pathology is the most
      severe feature of SMA, other organs and tissues, including the heart, are also
      known to be affected in both patients and animal models. Here, we provide new
      insights into changes occurring in the heart, predominantly at pre- and early
      symptomatic ages, in the Taiwanese mouse model of severe SMA. Thinning of the
      interventricular septum and dilation of the ventricles occurred at pre- and early
      symptomatic ages. However, the left ventricular wall was significantly thinner in
      SMA mice from birth, occurring prior to any overt neuromuscular symptoms.
      Alterations in collagen IV protein from birth indicated changes to the basement
      membrane and contributed to the abnormal arrangement of cardiomyocytes in SMA
      hearts. This raises the possibility that developmental defects, occurring
      prenatally, may contribute to cardiac pathology in SMA. In addition,
      cardiomyocytes in SMA hearts exhibited oxidative stress at pre-symptomatic ages
      and increased apoptosis during early symptomatic stages of disease. Heart
      microvasculature was similarly decreased at an early symptomatic age, likely
      contributing to the oxidative stress and apoptosis phenotypes observed. Finally,
      an increased incidence of blood retention in SMA hearts post-fixation suggests
      the likelihood of functional defects, resulting in blood pooling. These
      pathologies mirror dilated cardiomyopathy, with clear consequences for heart
      function that would likely contribute to potential heart failure. Our findings
      add significant additional experimental evidence in support of the requirement to
      develop systemic therapies for SMA capable of treating non-neuromuscular
      pathologies.

PMID- 29473160
TI  - Deciphering the roles of FOXO1 in human neoplasms.
AB  - Neoplasms constituted an enormous burden and contributed to an estimated 8.2
      million deaths in 2012 worldwide. FOXO1 (forkhead box O1), a member of the
      forkhead box (FOX) family, is a transcriptional factor involved in diverse
      cellular functions. Herein, we concentrate on recent studies of the
      antineoplastic roles of FOXO1 in neoplasms. This article may serve as a guide for
      future research and identify FOXO1 as a potent therapeutic target in neoplasms.

PMID- 29473161
TI  - Depressive Symptoms, Criticism, and Counter-Criticism in Marital Interactions.
AB  - Although people with depressive symptoms face criticism, hostility, and rejection
      in their close relationships, we do not know how they respond. Following
      interpersonal theories of depression, it might be expected that depressive
      symptoms would be associated with a tendency to receive and also to express
      criticism toward one's spouse, and that at least some of this criticism would be
      a contingent response to criticism received (i.e., "counter-criticism"). However,
      other research has determined that depressive symptoms/behaviors suppress partner
      criticism, suggesting that depressed people might respond to partner criticism
      similarly, by subsequently expressing less criticism. In a sample of 112 married
      couples, partial correlations, regressions, and Actor-Partner Interdependence
      Modeling indicated that lower criticism and counter-criticism expression during a
      laboratory marital interaction task was associated with higher depressive
      symptoms, especially when such individuals were clinically depressed.
      Furthermore, during a separate and private Five-Minute Speech Sample, lower
      criticism by partners was associated with higher depressive symptoms, especially
      when those who chose the interaction topic were also clinically depressed. All
      analyses controlled for relationship adjustment. These results suggest that
      spouses with higher depressive symptoms and clinical depression diagnoses may be
      suppressing otherwise ordinary criticism expression toward their nondepressed
      partners; furthermore, nondepressed partners of depressed people are especially
      likely to display less criticism toward their spouse in a private task.

PMID- 29473164
TI  - The glucose-lowering effects of exogenous ketones: is there therapeutic
      potential?

PMID- 29473162
TI  - Tumor-associated autoantibodies as early detection markers for ovarian cancer? A
      prospective evaluation.
AB  - Immuno-proteomic screening has identified several tumor-associated autoantibodies
      (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer,
      with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent
      examples. However, the early detection potential of these AAbs has been
      insufficiently explored in prospective studies. We performed ELISA measurements
      of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian
      cancer and 705 matched controls from the European EPIC cohort, using serum
      samples collected up to 36 months prior to diagnosis under usual care. CA125 was
      measured using electrochemo-luminiscence. Diagnostic discrimination statistics
      were calculated by strata of lead-time between blood collection and diagnosis.
      With lead times <=6 months, ovarian cancer detection sensitivity at 0.98
      specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and
      NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous
      tumors). However, at longer lead-times, the ability of these AAb markers to
      distinguish future ovarian cancer cases from controls declined rapidly; at lead
      times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01
      0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and
      CA125 did not improve detection sensitivity at equal level of specificity. The
      added value of these selected AAbs as markers for ovarian cancer beyond CA125 for
      early detection is therefore limited.

PMID- 29473165
TI  - Neural oscillations in the infralimbic cortex after electrical stimulation of the
      amygdala. Relevance to acute stress processing.
AB  - The stress system coordinates the adaptive reactions of the organism to
      stressors. Therefore, dysfunctions in this circuit may correlate to anxiety
      related disorders, including depression. Comprehending the dynamics of this
      network may lead to a better understanding of the mechanisms that underlie these
      diseases. The central nucleus of the amygdala (CeA) activates the hypothalamic
      pituitary-adrenal axis and brainstem nodes by triggering endocrine, autonomic and
      behavioral stress responses. The medial prefrontal cortex plays a significant
      role in regulating reactions to stressors, and is specifically important for
      limiting fear responses. Brain oscillations reflect neural systems activity.
      Synchronous neuronal assemblies facilitate communication and synaptic plasticity,
      mechanisms that cooperatively support the temporal representation and long-term
      consolidation of information. The purpose of this article was to delve into the
      interactions between these structures in stress contexts by evaluating changes in
      oscillatory activity. We particularly analyzed the local field potential in the
      infralimbic region of the medial prefrontal cortex (IL) in urethane-anesthetized
      rats after the electrical activation of the central nucleus of the amygdala by
      mimicking firing rates induced by acute stress. Electrical CeA activation induced
      a delayed, but significant, change in the IL, with prominent slow waves
      accompanied by an increase in the theta and gamma activities, and spindles. The
      phase-amplitude coupling of both slow waves and theta oscillations significantly
      increased with faster oscillations, including theta-gamma coupling and the
      nesting of spindles, theta and gamma oscillations in the slow wave cycle. These
      results are further discussed in neural processing terms of the stress response
      and memory formation.

PMID- 29473163
TI  - Binocular response modulation in the lateral geniculate nucleus.
AB  - The dorsal lateral geniculate nucleus of the thalamus (LGN) receives the main
      outputs of both eyes and relays those signals to the visual cortex. Each retina
      projects to separate layers of the LGN so that each LGN neuron is innervated by a
      single eye. In line with this anatomical separation, visual responses of almost
      all of LGN neurons are driven by one eye only. Nonetheless, many LGN neurons are
      sensitive to what is shown to the other eye as their visual responses differ when
      both eyes are stimulated compared to when the driving eye is stimulated in
      isolation. This, predominantly suppressive, binocular modulation of LGN responses
      might suggest that the LGN is the first location in the primary visual pathway
      where the outputs from the two eyes interact. Indeed, the LGN features several
      anatomical structures that would allow for LGN neurons responding to one eye to
      modulate neurons that respond to the other eye. However, it is also possible that
      binocular response modulation in the LGN arises indirectly as the LGN also
      receives input from binocular visual structures. Here we review the extant
      literature on the effects of binocular stimulation on LGN spiking responses,
      highlighting findings from cats and primates, and evaluate the neural circuits
      that might mediate binocular response modulation in the LGN.

PMID- 29473166
TI  - Capillary morphogenesis protein 2 is a novel prognostic biomarker and plays
      oncogenic roles in glioma.
AB  - Capillary morphogenesis protein 2 (CMG2) was originally identified through its
      participation in capillary morphogenesis, and subsequently identified as the
      second receptor for anthrax toxin (ANTXR2). Although tumor-associated functions
      of CMG2 have also been reported, the clinical significance and functional
      mechanism of CMG2 in glioma remain to be elucidated. We assessed the
      clinicopathological relevance of CMG2 in a cohort of 48 glioma patients as well
      as through public glioma databases, and explored the function of CMG2 using
      glioblastoma (GBM) models in vitro and in vivo. CMG2 overexpression was
      associated with increased tumor grade and poor patient survival. CMG2 promoted
      G2/M-phase transition during the cell cycle of GBM cells in vitro and contributed
      to tumor growth in vivo. We also observed that CMG2 is implicated in the
      activation of extracellular signal-regulated kinases (ERKs), epithelial
      mesenchymal transition (EMT), migration, and invasion in GBM cells.
      Transcriptomic analysis of GBM cells with or without CMG2 overexpression
      indicated that a panel of oncogenic signaling pathways was altered with CMG2
      upregulation, implying that CMG2 might orchestrate these signaling pathways to
      regulate the growth of GBM cells. Yes-associated protein 1 (YAP1) activity was
      enhanced by CMG2 overexpression but suppressed with CMG2 deficiency. Since YAP1
      is critically implicated in GBM, the oncogenic roles of CMG2 in GBM cells might
      thus be mediated, at least partially, by YAP1. Altogether, CMG2 functioned as an
      oncogene in glioma cells and is a potential prognostic biomarker or therapeutic
      target for the clinical treatment of glioma. Copyright (c) 2018 Pathological
      Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID- 29473167
TI  - Efferent projections of excitatory and inhibitory preBotzinger Complex neurons.
AB  - The preBotzinger Complex (preBotC), a compact medullary region essential for
      generating normal breathing rhythm and pattern, is the kernel of the breathing
      central pattern generator (CPG). Excitatory preBotC neurons in rats project to
      major breathing-related brainstem regions. Here, we provide a brainstem
      connectivity map in mice for both excitatory and inhibitory preBotC neurons.
      Using a genetic strategy to label preBotC neurons, we confirmed extensive
      projections of preBotC excitatory neurons within the brainstem breathing CPG
      including the contralateral preBotC, Botzinger Complex (BotC), ventral
      respiratory group, nucleus of the solitary tract, parahypoglossal nucleus,
      parafacial region (RTN/pFRG or alternatively, pFL /pFV ), parabrachial and
      Kolliker-Fuse nuclei, as well as major projections to the midbrain periaqueductal
      gray. Interestingly, preBotC inhibitory projections paralleled the excitatory
      projections. Moreover, we examined overlapping projections in the pons in detail
      and found that they targeted the same neurons. We further explored the direct
      anatomical link between the preBotC and suprapontine brain regions that may
      govern emotion and other complex behaviors that can affect or be affected by
      breathing. Forebrain efferent projections were sparse and restricted to specific
      nuclei within the thalamus and hypothalamus, with processes rarely observed in
      cortex, basal ganglia, or other limbic regions, e.g., amygdala or hippocampus. We
      conclude that the preBotC sends direct, presumably inspiratory-modulated,
      excitatory and inhibitory projections in parallel to distinct targets throughout
      the brain that generate and modulate breathing pattern and/or coordinate
      breathing with other behaviors, physiology, cognition, or emotional state.

PMID- 29473168
TI  - Structural basis for PDZ domain interactions in the post-synaptic density
      scaffolding protein Shank3.
AB  - The Shank proteins are crucial scaffolding elements of the post-synaptic density
      (PSD). One of the best-characterized domains in Shank is the PDZ domain, which
      binds to C-terminal segments of several other PSD proteins. We carried out a
      detailed structural analysis of Shank3 PDZ domain-peptide complexes, to
      understand determinants of binding affinity towards different ligand proteins.
      Ligand peptides from four different proteins were cocrystallized with the Shank3
      PDZ domain, and binding affinities were determined calorimetrically. In addition
      to conserved class I interactions between the first and third C-terminal peptide
      residue and Shank3, side chain interactions of other residues in the peptide with
      the PDZ domain are important factors in defining affinity. Structural
      conservation suggests that the binding specificities of the PDZ domains from
      different Shanks are similar. Two conserved buried water molecules in PDZ domains
      may affect correct local folding of ligand recognition determinants. The solution
      structure of a tandem Shank3 construct containing the SH3 and PDZ domains showed
      that the two domains are close to each other, which could be of relevance, when
      recognizing and binding full target proteins. The SH3 domain did not affect the
      affinity of the PDZ domain towards short target peptides, and the schizophrenia
      linked Shank3 mutation R536W in the linker between the domains had no effect on
      the structure or peptide interactions of the Shank3 SH3-PDZ unit. Our data show
      the spatial arrangement of two adjacent Shank domains and pinpoint affinity
      determinants for short PDZ domain ligands with limited sequence homology.

PMID- 29473170
TI  - Determination of physical health status and healthy lifestyle behaviors of
      individuals with mental illness.
AB  - PURPOSE: The aim of this study is to determine the physical health status and
      healthy lifestyle behaviors of individuals with mental illness. DESIGN AND
      METHODS: A descriptive research design was used. The sample of the study
      consisted of 115 individuals with mental illness. The Health Lifestyle Behaviors
      Scale II was used to assess the healthy lifestyle behaviors of the participants.
      FINDINGS: Of the individuals, 49.6% were found to have metabolic syndrome.
      Individuals with mental illness obtained the lowest score from the physical
      activity dimension of the scale. PRACTICE IMPLICATIONS: Individuals with mental
      illness need to receive education and support, especially in terms of nutrition
      and exercise.

PMID- 29473171
TI  - Nimodipine confers clinical improvement in two models of experimental autoimmune
      encephalomyelitis.
AB  - Multiple sclerosis is characterised by inflammatory neurodegeneration, with
      axonal injury and neuronal cell death occurring in parallel to demyelination.
      Regarding the molecular mechanisms responsible for demyelination and axonopathy,
      energy failure, aberrant expression of ion channels and excitotoxicity have been
      suggested to lead to Ca2+ overload and subsequent activation of calcium-dependent
      damage pathways. Thus, the inhibition of Ca2+ influx by pharmacological
      modulation of Ca2+ channels may represent a novel neuroprotective strategy in the
      treatment of secondary axonopathy. We therefore investigated the effects of the L
      type voltage-gated calcium channel blocker nimodipine in two different models of
      mouse experimental autoimmune encephalomyelitis (EAE), an established
      experimental paradigm for multiple sclerosis. We show that preventive application
      of nimodipine (10 mg/kg per day) starting on the day of induction had
      ameliorating effects on EAE in SJL/J mice immunised with encephalitic myelin
      peptide PLP139-151 , specifically in late-stage disease. Furthermore, supporting
      these data, administration of nimodipine to MOG35-55 -immunised C57BL/6 mice
      starting at the peak of pre-established disease, also led to a significant
      decrease in disease score, indicating a protective effect on secondary CNS
      damage. Histological analysis confirmed that nimodipine attenuated demyelination,
      axonal loss and pathological axonal beta-amyloid precursor protein accumulation
      in the cerebellum and spinal cord in the chronic phase of disease. Of note, we
      observed no effects of nimodipine on the peripheral immune response in EAE mice
      with regard to distribution, antigen-specific proliferation or activation
      patterns of lymphocytes. Taken together, our data suggest a CNS-specific effect
      of L-type voltage-gated calcium channel blockade to inflammation-induced
      neurodegeneration.

PMID- 29473172
TI  - Ceftriaxone-induced drug reaction mimicking acute splenic sequestration crisis in
      a child with hemoglobin SC disease.
AB  - BACKGROUND: Acute splenic sequestration crisis is a complication of sickle cell
      disease (SCD) occurring when intrasplenic red blood cell (RBC) sickling prevents
      blood from leaving the spleen, causing acute splenic enlargement. Although
      typically seen in young children, it has been reported in older children with
      hemoglobin (Hb)SC disease, eventually resulting in functional asplenia.
      Ceftriaxone is a frequently used antibiotic of choice for children with SCD,
      because of its efficacy against invasive pneumococcal disease. CASE REPORT: We
      report a case of a 9-year-old female with HbSC disease, who had a fatal reaction
      after receiving a dose of ceftriaxone in the outpatient clinic for fever. Her Hb
      level decreased abruptly from 9.3 to 2.3 mg/dL. RBC clumps with no visible
      hemolysis were observed in the postreaction sample. Autopsy examination revealed
      marked splenomegaly with acute congestion and sickled cells in the spleen and
      liver. Serologic testing revealed a positive direct antiglobulin test with
      polyspecific antibody, anti-C3, and anti-C3d, but negative with anti
      immunoglobulin G. Ceftriaxone-dependent RBC antibodies were detected in her serum
      and RBC eluate when tested in the presence of the drug. CONCLUSION: We report a
      new presentation of ceftriaxone-induced drug reaction in a patient with SCD
      mimicking an acute splenic sequestration crisis. Review of the literature for
      cases of ceftriaxone-induced drug reactions in pediatric patients revealed nine
      previously reported cases of ceftriaxone-induced immune hemolytic anemia in
      children with SCD since 1995, but none with an initial presentation suggestive of
      acute splenic sequestration crisis.

PMID- 29473169
TI  - Animal models of Wilson disease.
AB  - Wilson disease (WD) is an autosomal recessive disorder of copper metabolism
      manifesting with hepatic, neurological and psychiatric symptoms. The limitations
      of the currently available therapy for WD (particularly in the management of
      neuropsychiatric disease), together with our limited understanding of key aspects
      of this illness (e.g. neurological vs. hepatic presentation) justify the ongoing
      need to study WD in suitable animal models. Four animal models of WD have been
      established: the Long-Evans Cinnamon rat, the toxic-milk mouse, the Atp7b
      knockout mouse and the Labrador retriever. The existing models of WD all show
      good similarity to human hepatic WD and have been helpful in developing an
      improved understanding of the human disease. As mammals, the mouse, rat and
      canine models also benefit from high homology to the human genome. However,
      important differences exist between these mammalian models and human disease,
      particularly the absence of a convincing neurological phenotype. This review will
      first provide an overview of our current knowledge of the orthologous genes
      encoding ATP7B and the closely related ATP7A protein in C. elegans, Drosophila
      and zebrafish (Danio rerio) and then summarise key characteristics of rodent and
      larger mammalian models of ATP7B-deficiency.

PMID- 29473173
TI  - Ultraviolet light-based pathogen inactivation and alloimmunization after platelet
      transfusion: results from a randomized trial.
AB  - BACKGROUND: The current study explored whether pathogen-reduction treatment of
      platelet components before transfusion would decrease the risk of
      alloimmunization. STUDY DESIGN AND METHODS: Study participants were patients with
      hematologic cancer who were included in two parallel, randomized clinical trials
      testing pathogen-reduction treatment versus conventional platelets using the
      Mirasol or Intercept pathogen-reduction systems. Patients who had a baseline,
      pretransfusion sample and a follow-up, posttransfusion sample were included in
      the study (n = 179 patients in each study arm). Human leukocyte antigen antibody
      levels were determined using a commercial multianalyte, bead-based assay.
      RESULTS: The rate of human leukocyte antigen Class I alloimmunization at the
      clinical sites in recipients of conventional platelets was low at the highest
      assay cutoff (range, 1.2%-5.9%). Consistent with prior studies, human leukocyte
      antigen antibodies were first detected from 3 to 35 days after transfusion. There
      were no statistically significant differences between alloimmunization rates in
      patients who received pathogen-reduction treatment versus conventional platelet
      transfusions. Although he difference was not statistically significant, the
      effect size for protection from alloimmunization was greatest for high-level
      human leukocyte antigen Class I antibodies (approximately threefold) in the
      Intercept-treated patients compared with those who received conventional
      platelets. In the Mirasol study, only two patients and one patient in the control
      group developed medium-level or high-level antibodies, respectively, so it was
      impossible to determine an effect size for potential protection. CONCLUSIONS: The
      current study was not sufficiently powered to determine whether pathogen
      reduction treatment provides protection from human leukocyte antigen
      alloimmunization in platelet transfusion recipients. The data presented will be
      useful in the design of future trials and endpoints powered to detect a
      protective effect.

PMID- 29473174
TI  - Variation in red cell transfusion decisions in the intensive care unit - a
      nationwide survey in the Netherlands.
AB  - BACKGROUND AND OBJECTIVES: Most guidelines recommend a restrictive transfusion
      trigger of 7 g/dl. It is unclear whether this resulted in more uniform
      transfusion practices. The primary objective was to uncover the extent of
      variation in transfusion decisions within four scenarios of critically ill
      patients among critical care physicians in the Netherlands. MATERIALS AND
      METHODS: An online survey comprising four different hypothetical clinical
      scenarios was sent to all members of the Dutch Society of Intensive Care. The
      scenarios represented patients with acute myocardial infarction (Hb 8.5 g/dl),
      abdominal sepsis (Hb 7.1 g/dl), traumatic brain injury (TBI) (Hb 7.9 g/dl) and
      post-surgical complications (Hb 7.3 g/dl). The questions explored the decision
      whether or not to transfuse and a ranking of clinical characteristics playing the
      most important role in the transfusion decision. RESULTS: A total of 224 members
      (22%) participated in the study of whom 188 (84%) completed all questions. The
      percentages of respondents that decided to transfuse ranged from 25.9% in the
      scenario with TBI to 81.6% in the scenario with post-surgical complications. Most
      controversy was seen in the scenario with sepsis for which 43.2% decided to
      transfuse, whereas 56.8% decided not to. Haemoglobin level, diagnosis and
      haemodynamics were most important for the transfusion decision in all scenarios.
      CONCLUSIONS: Physicians decided differently on red-blood-cell transfusion given
      the clinical scenarios and weighed clinical characteristics differently in their
      transfusion decisions. These findings suggest there still is substantial
      variation in critical care transfusion practice.

PMID- 29473175
TI  - Breaking the oncostatin M feed-forward loop to suppress metastasis and therapy
      failure.
AB  - Deciphering the complex milieu that makes up the tumor microenvironment (TME) and
      the signaling engaged by TME cytokines continues to provide novel targets for
      therapeutic intervention. The IL-6 family member oncostatin M (OSM) has recently
      emerged as a potent driver of tumorigenesis, metastasis, and therapy failure,
      molecular programs most frequently attributed to IL-6 itself. In a recent issue
      of The Journal of Pathology, Kucia-Tran et al describe how elevated oncostatin M
      receptor (OSMR) expression results in a feed-forward loop involving the de novo
      production of both OSM and OSMR to facilitate aggressive properties in squamous
      cell carcinoma (SCC). Here, we discuss how new findings implicating OSM in
      conferring aggressive cancer cell properties can be leveraged to suppress
      metastatic outgrowth and therapy failure in SCC as well as other cancers.
      Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 29473176
TI  - The B allele with a 5.8 kb deletion in intron 1 of the ABO gene is the major
      allele in Japanese individuals with Bm and A1 Bm phenotypes.
AB  - Bm and A1 Bm phenotypes are the most frequent ABO variants in the Japanese
      population. The B antigen on Bm red blood cells is only detectable by adsorption
      and elution tests, and plasma B-transferase activity is usually detected at half
      or less levels compared with that of common B. Recently, a B allele lacking an
      erythroid cell-specific transcription enhancer in intron 1 of the ABO gene was
      identified from individuals with Bm and A1 Bm phenotypes, which could explain the
      unique serologic properties of Bm . In the Japanese Red Cross Society, eight
      Blood Centers tested blood samples from donors throughout Japan and collected
      blood samples from 888 Bm and 415 A1 Bm individuals. DNA analysis revealed that
      1300 of 1303 (99.77%) individuals had the B allele with a 5.8 kb deletion (c.28 +
      5110_10889del), which included the enhancer element.

PMID- 29473177
TI  - Manufacture of endothelial colony-forming progenitor cells from steady-state
      peripheral blood leukapheresis using pooled human platelet lysate.
AB  - BACKGROUND: Endothelial colony-forming progenitor cells (ECFCs) are promising
      candidates for cell therapies. However, ECFC translation to the clinic requires
      optimized isolation and manufacture technologies according to good manufacturing
      practice (GMP). STUDY DESIGN AND METHODS: ECFCs were manufactured from steady
      state peripheral blood (PB) leukapheresis (11 donors), using GMP-compliant
      technologies including pooled human platelet (PLT) lysate, and compared to human
      umbilical cord endothelial cells, human aortic endothelial cells, and human
      cerebral microvascular endothelial cells. Specific variables assessed were growth
      kinetics, phenotype, trophic factors production, stimulation of tube formation,
      and Dil-AcLDL uptake. RESULTS: ECFCs could be isolated from PB leukapheresis
      units with mean processed volume of 5411 mL and mean white blood cell (WBC)
      concentration factor of 8.74. The mean frequency was 1.44 * 10-8 ECFCs per WBC,
      corresponding to a mean of 177.8 ECFCs per apheresis unit. Expandable for up to
      12 cumulative population doublings, calculated projection showed that
      approximately 730 * 103 ECFCs could be manufactured from 1 apheresis unit. ECFCs
      produced epidermal growth factor, hepatocyte growth factor, vascular endothelial
      growth factor (VEGF)-A, PLT-derived growth factor-B, interleukin-8, and monocyte
      chemoattractant protein-1, featured high potential for capillary-like tubes
      formation, and showed no telomerase activity. They were characterized by CD29,
      CD31, CD44, CD105, CD117, CD133, CD144, CD146, and VEGF-R2 expression, with the
      most common subpopulation CD34+CD117-CD133-. Compared to controls, ECFCs featured
      greater Dil-AcLDL uptake and higher expression of CD29, CD31, CD34, CD44, CD144,
      and VEGF-R2. CONCLUSIONS: Here we show that isolation of ECFCs with proangiogenic
      profile from steady-state PB leukapheresis is feasible, marking a first step
      toward ECFC product manufacture according to GMP.

PMID- 29473178
TI  - PAS-C platelets contain less plasma protein, lower anti-A and anti-B titers, and
      decreased HLA antibody specificities compared to plasma platelets.
AB  - BACKGROUND: Platelets (PLTs) collected and stored in PLT additive solution
      Intersol (PAS-C) are presumed to reduce recipient exposure to donor plasma
      components; however, the effects of PAS-C on PLT supernatant composition are
      poorly defined. Therefore, we compared the total protein concentration,
      isohemagglutinin titers, and HLA antibodies in supernatants of PAS-C PLTs to
      plasma PLTs. STUDY DESIGN AND METHODS: Apheresis PLTs from group O blood donors
      were collected into either 100% donor plasma (n = 50) or a mixture of 65% PAS
      C/35% donor plasma (n = 50). Within 12 hours of collection, samples of the PLT
      supernatant were frozen and stored. PLT supernatants were assayed for total
      protein concentration and anti-A and anti-B titers and screened for HLA
      antibodies. Samples positive for HLA antibodies were further tested using single
      antigen bead assays to determine antibody strength and specificity. RESULTS:
      Supernatants of PAS-C PLTs had significantly lower total protein concentration
      and anti-A and anti-B titers compared to plasma PLTs. There was no significant
      difference in the number of HLA antibody screen-positive PAS-C (3/50) compared to
      plasma PLT supernatants (2/50); however, the HLA antibody screen-positive
      supernatants of PAS-C PLTs had fewer HLA specificities (2) compared to those of
      the plasma PLTs (18). CONCLUSION: Decreased plasma proteins likely underlie lower
      rates of allergic and febrile, nonhemolytic transfusion reactions from the
      infusion of PAS-C PLTs. Decreased anti-A and anti-B titers may prevent hemolysis
      from minor ABO mismatch. Lower HLA antibody specificities may mitigate
      transfusion-related acute lung injury.

PMID- 29473179
TI  - Does docetaxel prolong survival of patients with non-metastatic castration
      resistant prostate cancer?
AB  - BACKGROUND: Guidelines define docetaxel as a first-line therapeutic option for
      metastatic castration-resistant prostate cancer (mCRPC). However, the role of
      docetaxel in non-metastatic castration-resistant prostate cancer (nmCRPC) has not
      been fully investigated. The aim of this retrospective study was to evaluate the
      potential role of docetaxel in nmCRPC. Clinical outcomes including overall
      survival were compared between CRPC patients who had docetaxel introduced while
      in nonmetastatic versus metastatic diseases. METHODS: A total of 98 CRPC patients
      had docetaxel therapy. Of these 46 patients received docetaxel for nmCRPC, and 52
      had distant metastases. Clinical outcomes from the time of diagnosis of CRPC were
      compared retrospectively between groups. RESULTS: The median observation period
      after the diagnosis of CRPC in these patients was 42 months (range, 3-166).
      Overall survival (OS) was significantly longer in the nmCRPC group than in the
      mCRPC group (not reached vs 52.2 months, respectively, P = 0.006). Multivariate
      analysis showed that longer time to CRPC, docetaxel use in nmCRPC, and use of
      abiraterone acetate and/or enzalutamide were significant predictors for improved
      OS (P = 0.04, 0.019 and 0.002, respectively). The incidence and profile of
      adverse events did not differ significantly between groups. CONCLUSIONS: Earlier
      induction of docetaxel in nmCRPC patients may prolong OS. Further prospective
      studies in more patients will be required to confirm our findings.

PMID- 29473180
TI  - Faces presenting sadness enhance self-control abilities in gifted adolescents.
AB  - Self-regulation skills refer to processes allowing emotional and cognitive
      adaptation of the individual. Some gifted adolescents are known for their
      imbalance between high intellectual abilities and low emotional skills. Thus,
      this study aimed at examining the interplay between emotion and cognition in
      gifted and non-gifted adolescents. A stop-signal task, a response inhibition task
      including neutral, happy, or sad faces as signal triggering inhibition, was
      administered to 19 gifted and 20 typically developing male adolescents (12-18
      years old). Gifted adolescents showed lower response inhibition abilities than
      non-gifted adolescents in the neutral and happy face conditions. Sad faces in
      gifted adolescents were associated with higher response inhibition compared to
      happy condition. In typically developing adolescents, emotional information
      (happy or sad faces) was related to lower response inhibition compared to neutral
      face condition. This study highlights that gifted adolescents present different
      self-regulation skills than their typically developing peers. Statement of
      contribution What is already known on this subject? Some gifted adolescents
      present higher intellectual abilities alongside with lower socio-emotional
      skills. Self-regulation skills refer to processes allowing emotional and
      cognitive adaptation. Self-regulation skills might help to understand gifted
      adolescents, but remain scarcely studied. What does this study adds? Task
      relevant emotional information impaired cognitive control in typically developing
      adolescents. Gifted adolescents are able to use sad faces to enhance their
      cognitive control abilities.

PMID- 29473181
TI  - Bridging to a Long-Term Ventricular Assist Device With Short-Term Mechanical
      Circulatory Support.
AB  - Implanting short-term mechanical circulatory support (MCS) devices as a bridge-to
      decision is increasingly popular. However, outcomes have not been well studied in
      patients who receive short-term MCS before receiving long-term left ventricular
      assist device (LVAD) support. We analyzed outcomes in our single-center
      experience with long-term continuous-flow (CF)-LVAD recipients with pre
      implantation short-term MCS. From November 2003 through March 2016, 526 patients
      (mean age, 54.7 +/- 13.5 years) with chronic heart failure (mean ejection
      fraction, 21.7 +/- 3.6%) underwent implantation of either the HeartMate II (n =
      403) or the HeartWare device (n = 123). Before implantation, 269 patients
      received short-term MCS with the TandemHeart, the Impella 2.5/5.0, an intra
      aortic balloon pump (IABP), venoarterial extracorporeal membrane oxygenation (VA
      ECMO), or the CentriMag. The short-term MCS patients were compared with the CF
      LVAD-only patients regarding preoperative demographics, incidence of
      postoperative complications, and long-term survival. The 269 patients received
      the following short-term MCS devices: 57 TandemHeart, 27 Impella, 172 IABP, 12 VA
      ECMO, and 1 CentriMag. Survival at 30 days, 6 months, 1 year, and 2 years was
      94.2, 87.2, 79.4, and 72.4%, respectively, for CF-LVAD-only patients versus 91.0,
      78.1, 73.4, and 65.6%, respectively, for short-term MCS + CF-LVAD patients (P =
      0.17). Within the short-term MCS group, survival at 24 months was poorest for
      patients supported with VA-ECMO or the TandemHeart (P = 0.03 for both), and
      survival across all four time points was poorest for patients supported with VA
      ECMO (P = 0.02). Short-term MCS was not an independent predictor of mortality in
      multivariate Cox regression models (hazard ratio = 1.12, 95% confidence interval
      = 0.84-1.49, P = 0.43). In conclusion, we found that using short-term MCS therapy
      except for VA-ECMO-as a bridge to long-term CF-LVAD support was not associated
      with poorer survival.

PMID- 29473182
TI  - The androgen receptor malignancy shift in prostate cancer.
AB  - BACKGROUND: Androgens and the androgen receptor (AR) are necessary for the
      development, function, and homeostatic growth regulation of the prostate gland.
      However, once prostate cells are transformed, the AR is necessary for the
      proliferation and survival of the malignant cells. This change in AR function
      appears to occur in nearly every prostate cancer. We have termed this the AR
      malignancy shift. METHODS: In this review, we summarize the current knowledge of
      the AR malignancy shift, including the DNA-binding patterns that define the
      shift, the transcriptome changes associated with the shift, the putative drivers
      of the shift, and its clinical implications. RESULTS: In benign prostate
      epithelial cells, the AR primarily binds consensus AR binding sites. In carcinoma
      cells, the AR cistrome is dramatically altered, as the AR associates with FOXA1
      and HOXB13 motifs, among others. This shift leads to the transcription of genes
      associated with a malignant phenotype. In model systems, some mutations commonly
      found in localized prostate cancer can alter the AR cistrome, consistent with the
      AR malignancy shift. Current evidence suggests that the AR malignancy shift is
      necessary but not sufficient for transformation of prostate epithelial cells.
      CONCLUSIONS: Reinterpretation of prostate cancer genomic classification systems
      in light of the AR malignancy shift may improve our ability to predict clinical
      outcomes and treat patients appropriately. Identifying and targeting the
      molecular factors that contribute to the AR malignancy shift is not trivial but
      by doing so, we may be able to develop new strategies for the treatment or
      prevention of prostate cancer.

PMID- 29473183
TI  - Peritoneal Dialysis Fluid-Induced Fragmentation of Golgi Apparatus as a
      Biocompatibility Marker.
AB  - In vitro biocompatibility assessments that consider physiologically appropriate
      conditions of cell exposure to peritoneal dialysis fluids (PDFs) are still
      awaited. In this study, we found that fragmentation of Golgi apparatus occurred
      in a pH-dependent manner within 30-min exposure to five distinct commercially
      available PDFs, which showed no marked difference in their effects on cell
      viability in the conventional MTT assay. Fluorescence microscopy analysis of
      labeling antibody against cis-Golgi protein GM130 indicated that the stacked
      cisternal structure was maintained in the perinuclear area of both M199 culture
      medium and a neutral-pH PDF groups. However, this specific structure became
      partially disassembled over time even in a neutral-pH PDF, and fragmentation was
      markedly enhanced in cells exposed to neutralized-pH PDFs in correspondence with
      their intracellular pH; moreover, in acidic PDFs, Golgi staining was diffuse and
      scattered in the entire cytoplasm and showed partial aggregation. The Golgi
      fragmentation markedly observed with the neutralized PDFs could be reversed by
      replacing either the media with a neutral-pH medium or a mixture of PDF and PD
      effluent (PDF) in a gradient manner mimicking clinical conditions. Furthermore,
      although weaker than pH effect, notable effects of other PDF-related factors were
      also observed after 30-min exposure to pH-adjusted PDFs. Lastly, the results of
      studies conducted using MAPK/SAPK inhibitors indicated that the mechanism
      underlying the Golgi fragmentation described here differs from that associated
      with the fragmentation that occurs at the G2/M checkpoint in the cell cycle. We
      conclude that Golgi fragmentation is suitable for rapid biocompatibility
      assessment of PDF not only because of its strong pH dependence but also because
      the fragmentation is recognizably affected by PDF constituents.

PMID- 29473184
TI  - Quantitative determination of risperidone, paliperidone and olanzapine in human
      serum by liquid chromatography-tandem mass spectrometry coupled with on-line
      solid-phase extraction.
AB  - A recent guideline recommends therapeutic drug monitoring for risperidone,
      paliperidone and olanzapine, which are frequently used second-generation
      antipsychotics. We developed a simple high-performance liquid chromatography
      tandem mass spectrometry coupled with an online solid-phase extraction method
      that can be used to measure risperidone, paliperidone and olanzapine using small
      (40 MUL) samples. The analytes were extracted from serum samples automatically
      pre-concentrated and purified by C8 (5 MUm, 2.1 * 30 mm) solid-phase extraction
      cartridges, then chromatographed on an XbidgeTM C18 column (3.5 MUm, 100 * 2.1
      mm) thermostatted at 30 degrees C with a mobile phase consisting of 70%
      acetonitrile and 30% ammonium hydroxide 1% solution at an isocratic flow rate of
      0.3 mL/min, and detected with tandem mass spectrometry. The assay was validated
      in the concentration range from 2.5 to 160 ng/mL. Intra- and inter-day precision
      for all analytes was between 1.1 and 8.2%; method accuracy was between 6.6 and
      7.6%. The risperidone and paliperidone assay was compared with a high-performance
      liquid chromatography-ultraviolet assay currently used in our hospital for
      risperidone and paliperidone therapeutic drug monitoring, and the results of
      weighted Deming regression analysis showed good agreement. For the olanzapine
      assay, we compared 20 samples in separate re-assays on different days; all the
      relative errors were within the 20% recommended limit.

PMID- 29473185
TI  - Spectrum-effect relationship between HPLC fingerprints and hypolipidemic effect
      of Curcuma aromatica.
AB  - Curcuma aromatica is used as a traditional Chinese medicine, and it is mainly
      distributed in Guangxi, China. In this study, 10 batches of C. aromatica were
      collected from different origins in Guangxi. The fingerprints were established by
      HPLC technique to investigate the quality stability of C. aromatica. The spectrum
      effect relationship between HPLC fingerprints and hypolipidemic effect of C.
      aromatica was assessed by similarity analysis, gray relational analysis and
      multiple linear regression analysis. From the results, the similarity values
      between each batch of C. aromatica and reference fingerprint were >0.880,
      indicating the good quality stability of the 10 batches of C. aromatica. Twenty
      common peaks were selected as the fingerprints to evaluate the quality and
      hypolipidemic effect of C. aromatica. The results of spectrum-effect relationship
      showed that peaks 10, 18, 13, 15 and 17 in the fingerprints were closely related
      to hypolipidemic effect. This study successfully established the spectrum-effect
      relationship between HPLC fingerprints and hypolipidemic effect of C. aromatica,
      which provided methods for quality control and more effectively studies on
      bioactive compounds of C. aromatica. It could also provide a new simple and
      effective method for utilizing the fingerprints to optimize the Chinese
      prescription and develop traditional Chinese medicine.

PMID- 29473186
TI  - Being in safe hands: Patients' perceptions of how cancer services may support
      psychological well-being.
AB  - AIMS: To explore how cancer services may positively promote and support patients'
      well-being throughout treatment. Specifically to identify components of care that
      are important to patients and meet their needs. BACKGROUND: Patients commonly
      experience stress and uncertainty during their cancer journey which can have a
      negative impact on their psychological health and quality of life. Comparatively,
      little is known about how patients may experience positive well-being during
      their treatment experience. DESIGN: Qualitative study using semi-structured
      interviews. METHODS: Interviews were conducted between 2014 - 2015 with a
      purposive sample of 30 individuals who were at the beginning, middle or end of
      treatment for lung, colorectal and head and neck cancer. The majority were
      outpatients and receiving radiotherapy, chemotherapy or a combination of these.
      The recordings were analysed using thematic analysis. RESULTS: Patients may
      obtain a range of positive health benefits derived from contact with staff,
      patients and public. Positive emotional gains were based on "being in safe hands"
      and part of the collective effort to eradicate cancer. This appeared to assist
      patients achieve favourable treatment responses, however, a range of factors
      encouraged and hindered them to express concerns. CONCLUSION: Interactions with
      staff, patients and the hospital environment supported well-being in those
      receiving cancer treatment. Findings demonstrate additional areas for research
      including the development of interventions to facilitate peer support and the
      implementation of communication strategies that promote well-being.

PMID- 29473187
TI  - Residents teaching medical students: creating a learner network.

PMID- 29473188
TI  - Influence of CAD/CAM fabrication on denture surface properties.
AB  - Three main properties are responsible for the microbial attractiveness of denture
      surfaces: roughness, hydrophilicity and free surface energy. This study
      investigated whether CAD/CAM-fabricated dentures are more favourable for these
      surface properties than conventionally fabricated dentures. The mucosal surface
      roughness of 54 standardised study dentures was measured using contact
      profilometry. The surface hydrophilicity and free surface energy of 70
      standardised denture resin specimens were determined by contact angle
      measurements. Both experimental settings compared AvaDent (AD), Baltic Denture
      System (BDS), Vita VIONIC (VV), Whole You Nexteeth (WN) and Wieland Digital
      Dentures (WDD) surfaces with conventionally manufactured denture surfaces
      (control group). These data were analysed using ANOVA together with Tukey's test
      or the Games-Howell post hoc test. All CAD/CAM dentures had lower mean surface
      roughness values than conventional dentures. For AD, VV, WN and WDD, the
      differences were statistically significant. Vita VIONIC (P < .001), coated WN (P
      < .001), AD (P = .023) and BDS specimens (P = .027) were significantly more
      hydrophilic than the control group. All measured surface energies were of similar
      magnitude (mean values between 31.82 and 33.68 mJ/m2 ), and only coated WN
      specimens had a significantly increased mean value (66.62 mJ/m2 , P < .001).
      Although most CAD/CAM dentures have smoother and more hydrophilic surfaces than
      conventional dentures, there is no difference in their free surface energy,
      except for coated dentures.

PMID- 29473189
TI  - An umbrella review of clinical practice guidelines for the management of patients
      with hip fractures and a synthesis of recommendations for the pre-operative
      period.
AB  - AIM: The aim of this review was to locate, retrieve and critically appraise
      practice guidelines for the management of hip fractures. Given increasing
      evidence that the early recognition and management of these fractures is integral
      to achieving optimal outcomes, recommendations for the pre-operative period were
      synthesized and compared. BACKGROUND: Hip fractures are associated with high
      rates of adverse outcomes and high healthcare costs which has resulted in the
      development of multiple practice guidelines to inform clinical decision-making.
      DESIGN: An umbrella review of practice guidelines was conducted which included a
      critical appraisal using the Appraisal of Guidelines, Research and Evaluation-II
      instrument and a synthesis of pre-operative management recommendations. DATA
      SOURCES: Multi-phased search for practice guidelines published in English using
      three bibliographic databases; three guideline network websites and three
      healthcare safety and quality organization websites with no date limit applied.
      Search was supplemented by contacting front-line knowledge users and content
      experts. REVIEW METHODS: Steps for evidence-informed practice were followed: form
      question then search for, appraise and synthesize the evidence. RESULTS: Five
      practice guidelines were appraised revealing significant variability in quality.
      The largest variability was in "rigour of development". Recommendations for pre
      operative management were grouped into six categories: timing of surgery,
      expedited patient management, identification and treatment of correctable co
      morbidities, pain management, preventative measures and multidisciplinary
      management. CONCLUSION: Results of this review illustrate that not all practice
      guidelines are of equal quality. Given the costs associated with the development
      and maintenance of high-quality practice guidelines, such work may be more
      efficiently completed through international collaborations and then adapted for
      national and regional healthcare contexts.

PMID- 29473190
TI  - Seven novel COL7A1 mutations identified in patients with recessive dystrophic
      epidermolysis bullosa from Mexico.
AB  - Recessive dystrophic epidermolysis bullosa (RDEB; OMIM #226600) is one of the
      most devastating subtypes of epidermolysis bullosa, a group of skin and mucous
      membrane blistering disorders often associated with extracutaneous
      manifestations. RDEB is caused by mutations in COL7A1, the gene encoding type VII
      collagen (C7), and to date over 700 different mutations in the 8835 nucleotides
      constituting the open reading frame or adjacent exon-intron boundaries of COL7A1
      have been described. We used targeted next-generation sequencing to identify
      seven previously unreported mutations in a cohort of 17 Mexican patients who were
      diagnosed with RDEB based on clinical presentation and immunoepitope mapping. Our
      study expands the spectrum of mutations identified in this cohort, including
      those suitable for emerging therapies reliant on precise genotyping.

PMID- 29473192
TI  - Thinness and muscularity internalization: Associations with disordered eating and
      muscle dysmorphia in men.
AB  - OBJECTIVE: The tripartite influence model of body image identifies
      internalization of societal body ideals as a risk factor for developing body
      dissatisfaction, and subsequent disordered eating behavior. In men,
      internalization of two dimensions of body image ideals, thinness and muscularity,
      is associated with body dissatisfaction and eating concerns. However, it is
      unknown how thinness and muscularity internalization interact in predicting
      muscle dysmorphia and disordered eating in men. METHOD: Data were collected
      online from 180 undergraduate men, with ages ranging from 18 to 33 years (19.6,
      SD = 2.6). Regression models were used to test the interactive effects of
      thinness and muscularity internalization on (a) muscle dysmorphia symptoms and
      (b) disordered eating. Subsequent simple slope analyses probed effects at the
      mean, and +/-1 standard deviation of thinness internalization. RESULTS:
      Muscularity and thinness internalization were independently positively related to
      muscle dysmorphia symptoms and disordered eating. Additionally, a significant
      interaction revealed that muscularity internalization was increasingly related to
      muscle dysmorphia symptoms as thinness internalization decreased. DISCUSSION: Men
      who internalized the muscular ideal had higher levels of muscle dysmorphia when
      they did not highly internalize the thin ideal. However, greater internalization
      of both the muscularity and thin ideal independently may be most relevant in the
      development of disordered eating in men. Future research is needed to explore
      variability in experiences of muscle dysmorphia compared with disordered eating
      in males.

PMID- 29473191
TI  - Body composition and physical fitness in women with bulimia nervosa or binge
      eating disorder.
AB  - OBJECTIVE: Knowledge about physical fitness in women with bulimia nervosa (BN) or
      binge-eating disorder (BED) is sparse. Previous studies have measured physical
      activity largely through self-report, and physical fitness variables are mainly
      restricted to body mass index (BMI) and bone mineral density. We expanded the
      current knowledge in these groups by including a wider range of physical fitness
      indicators and objective measures of physical activity, assessed the influence of
      a history of anorexia nervosa (AN), and evaluated predictive variables for
      physical fitness. METHOD: Physical activity, blood pressure, cardiorespiratory
      fitness (CRF), muscle strength, body composition, and bone mineral density were
      measured in 156 women with BN or BED, with mean (SD) age 28.4 years (5.7) and BMI
      25.3 (4.8) kg m-2 . RESULTS: Level of physical activity was higher than normative
      levels, still <50% met the official physical activity recommendation. Fitness in
      women with BN were on an average comparable with recommendations or normative
      levels, while women with BED had lower CRF and higher BMI, VAT, and body fat
      percentage. We found 10-12% with masked obesity. A history of AN did not predict
      current physical fitness, still values for current body composition were lower
      when comparing those with history of AN to those with no such history.
      DISCUSSION: Overall, participants with BN or BED displayed adequate physical
      fitness; however, a high number had unfavorable CRF and body composition. This
      finding calls for inclusion of physical fitness in routine clinical examinations
      and guided physical activity and dietary recommendations in the treatment of BN
      and BED.

PMID- 29473193
TI  - Pigmented onychomatricoma: a rare mimic of subungual melanoma.

PMID- 29473194
TI  - Radiographic measurements of the hindlimbs in crab-eating foxes (Cerdocyon thous,
      Linnaeus, 1766).
AB  - Life expectancy of crab-eating foxes in captivity is approximately 11 years,
      which favours the development of diseases including orthopaedic disorders.
      However, to understand disorders that may affect these animals, it is worth
      determining a normal range of measurements. Therefore, this study aimed to
      evaluate radiographic measurements of joint angles of the hindlimbs and the ratio
      of patellar ligament length to patellar length in healthy crab-eating foxes.
      Fifteen captive crab-eating foxes (Cerdocyon thous), eight males and seven
      females, aged more than 1 year old, weighing 5.5-7.9 kg were used. Anatomic and
      mechanical femoral joint angles were assessed in ventrodorsal radiographic views,
      and mediolateral views were taken to measure patellar ligament length and
      patellar length, and the tibial plateau angle. The right and left hindlimbs were
      evaluated. All measurements were conducted in triplicate by the same
      investigator. No statistically significant differences were observed between
      sides in the radiographic measurements. The anatomic lateral proximal femoral
      angle and the anatomic lateral distal femoral angle recorded mean values of 95.43
      degrees  and 92.75 degrees , respectively. The mechanical lateral proximal
      femoral angle and the mechanical lateral distal femoral angle recorded mean
      values of 93.39 degrees  and 96.75 degrees , respectively. Inclination angles
      measured according to the Tomlinson, Hauptman A and Hauptman B methods were
      133.80 degrees , 147.32 degrees  and 128.63 degrees , respectively. The tibial
      plateau recorded 18.77 degrees , and the ratio of the patellar ligament length to
      the patellar length was 1.99. In conclusion, the collected data are important to
      characterize the normal values of crab-eating fox limbs.

PMID- 29473195
TI  - Determination of metoserpate, buquinolate, and diclofenac in pork, eggs, and milk
      using liquid chromatography-tandem mass spectrometry.
AB  - In this work, a method was developed for the simultaneous determination of
      residual metoserpate, buquinolate and diclofenac in pork, milk, and eggs. Samples
      were extracted with 0.1% formic acid in acetonitrile, defatted with n-hexane, and
      filtered prior to analysis using liquid chromatography-tandem mass spectrometry.
      The analytes were separated on a C18 column using 0.1% acetic acid and methanol
      as the mobile phase. The matrix-matched calibration curves showed good linearity
      over a concentration range of 5-50 ng/g with coefficients of determination (R2 )
      >=0.991. The intra- and inter-day accuracies (expressed as recovery percentage
      values) calculated using three spiking levels (5, 10, and 20 MUg/kg) were 80
      108.65 and 74.06-107.15%, respectively, and the precisions (expressed as relative
      standard deviation) were 2.86-13.67 and 0.05-11.74%, respectively, for the tested
      drugs determined in various matrices. The limits of quantification (1 and 2
      MUg/kg) were below the uniform residual level (0.01 mg/kg) set for compounds that
      have no specific maximum residue limit (MRL). The developed method was tested
      using market samples and none of the target analytes was detected in any of the
      samples. The validated method proved to be practicable for detection of the
      tested analytes in pork, milk, and eggs.

PMID- 29473196
TI  - CD30-positive primary cutaneous anaplastic large cell lymphoma with coexistent
      pseudocarcinomatous hyperplasia.
AB  - CD30-positive primary cutaneous anaplastic large cell lymphoma (C-ALCL) is an
      indolent type of cutaneous lymphoma with favourable clinical prognosis.
      Pseudocarcinomatous hyperplasia (PCH) is a rare benign epithelial condition that
      can resemble invasive squamous cell carcinoma both clinically and
      histopathologically. PCH predominantly occurs in CD30-positive
      lymphoproliferative disorders. We report a 75-year-old woman with PCH in a
      multifocal C-ALCL located on the scalp and right retroauricular area, which
      rapidly responded to treatment with psoralen ultraviolet A photochemotherapy.
      Comprehensive virological analyses for potential oncogenic viruses, including
      Epstein-Barr virus, human herpesvirus-8, human papillomaviruses, the recently
      discovered cutavirus and nine different human polyomaviruses, were negative.

PMID- 29473197
TI  - Heritability of the airway structure and head posture using twin study.
AB  - Inherited traits of obstructive sleep apnoea (OSA) may have link to the
      heritability of the airway anatomy. The aim of this study was to investigate
      heritability of the airway anatomy by comparing skeletal and soft tissue features
      of Korean monozygotic twins (MZ) and dizygotic twins (DZ). In total, 72
      participants (mean age, 41.5 +/- 5.9 years; 40 males, 32 females) including 48 MZ
      (24 pairs) and 24 DZ (12 pairs) with same sex were participated. The
      craniofacial, craniovertebral, hyoideal and pharyngeal parameters were measured
      using lateral cephalograms. The genetic analysis was performed using Falconer's
      method. High heritability was detected in the hyoid position and inclination of
      the cervical column. The velopharyngeal and hypopharyngeal dimensions showed
      higher heritability compared to those of the nasopharynx and oropharynx. The body
      mass index (BMI) had interactions with the nasopharyngeal and hypopharyngeal
      dimensions and length of the tongue and soft palate. The mandibular growth had
      correlations with the nasopharyngeal and hypopharyngeal dimensions. The vertical
      skeletal relationships appeared to have interaction with the nasopharyngeal,
      velopharyngeal and hypopharyngeal dimensions, as well as length of the tongue and
      soft palate. A forwarded inclination of the cervical columns was seen in
      connections with BMI and the nasopharyngeal and hypopharyngeal dimensions. The
      airway structures and head postures seemed to be under strong genetic controls.
      The airway dimensions had associations with BMI, head postures and skeletal
      structures which showed high heritability. Forwarded head postures would be
      physiological adaptations of compromised airway adequacy by increased BMI and
      retrognathia.

PMID- 29473198
TI  - Relationship between nurse psychological empowerment and job satisfaction: A
      systematic review and meta-analysis.
AB  - AIMS: This systematic review and meta-analysis aimed to synthesize and analyse
      studies that explored the relationship between the psychological empowerment and
      job satisfaction of nurses. BACKGROUND: Nurse turnover is an important cause of
      staff shortage. Job satisfaction is a major predictor of nurse turnover and is
      connected to the psychological empowerment of nurses. DESIGN: This systematic
      review and meta-analysis is based on the Joanna Briggs Institute guidelines. DATA
      SOURCES: A total of 1,572 articles on psychological empowerment and job
      satisfaction were retrieved from PubMed, PsycINFO, EMBASE and Web of Science. The
      articles were written in English and published before or by April 2017. METHODS:
      Studies on the relationship between psychological empowerment and job
      satisfaction were summarized. RESULTS: The majority of the included studies
      revealed that psychological empowerment and job satisfaction are significantly
      correlated. Only two studies showed that the two factors are not significantly
      correlated. The result of this meta-analysis is consistent with the results of
      most studies. One study reported that psychological empowerment partially
      mediates the structural empowerment and job satisfaction of school health nurses.
      Two studies, however, did not find that the mediating role of psychological
      empowerment between structural empowerment and job satisfaction. CONCLUSION: The
      results of this review provided evidence for the importance of psychological
      empowerment for the job satisfaction of among nurses. Exploring the correlation
      between psychological empowerment and job satisfaction can provide guidelines and
      recommendation for the development of strategies to promote nurse retention and
      alleviate nursing shortage.

PMID- 29473199
TI  - Glucosylsphingosine is a reliable response biomarker in Gaucher disease.

PMID- 29473200
TI  - Unusual inclusions in hemoglobin H disease post-splenectomy.

PMID- 29473201
TI  - Chronic neutrophilic leukemia.

PMID- 29473203
TI  - Case of combined nevus showing a speckled distribution pattern.

PMID- 29473202
TI  - Clinical significance of neutrophil gelatinase-associated lipocalin and galectin
      7 in tape-stripped stratum corneum of acne vulgaris.
AB  - The usefulness of stratum corneum neutrophil gelatinase-associated lipocalin and
      stratum corneum galectin-7 as biomarkers of acne vulgaris was studied. A
      comparison of neutrophil gelatinase-associated lipocalin levels on the cheeks of
      patients with acne vulgaris at the start of the study and at the time of symptom
      improvement showed a significant decrease. On the other hand, the galectin-7
      levels at the time of symptom improvement were significantly higher than those at
      the start of the study. Therefore, because the inflammation in the epidermis and
      hair follicles was reduced after therapy, as a result of the solution of the
      inflammatory eruptions caused by acne vulgaris, the neutrophil gelatinase
      associated lipocalin level also showed a significant decrease after therapy.
      These results suggest that stratum corneum neutrophil gelatinase-associated
      lipocalin may be useful as an objective biomarker of changes in acne vulgaris
      symptoms.

PMID- 29473204
TI  - MRI for the diagnosis of cardiac and liver iron overload in patients with
      transfusion-dependent thalassemia: An algorithm to guide clinical use when
      availability is limited.

PMID- 29473205
TI  - Trousseau syndrome associated with cutaneous squamous cell carcinoma.

PMID- 29473206
TI  - Association of Mac-2-binding protein glycosylation isomer level with nutritional
      status in chronic liver disease.
AB  - BACKGROUND AND AIM: Mac-2-binding protein glycosylation isomer (M2BPGi) was
      recently identified as a serum glycobiomarker for liver fibrosis. However, the
      relationship between M2BPGi and malnutrition in patients with chronic liver
      disease (CLD) is unknown. We aimed to evaluate whether M2BPGi could be a
      surrogate marker for malnutrition in patients with CLD. METHODS: In total, 338
      outpatients with CLD were enrolled (median age: 67 years). We evaluated the
      associations among liver fibrosis markers (M2BPGi, fibrosis-4 index, and
      aspartate aminotransferase-to-platelet count ratio index), Child-Pugh stages, and
      nutritional status markers. RESULTS: The median value (range) of serum M2BPGi
      levels was 0.94 cut-off index (COI) (0.22-11.57) in chronic hepatitis and Child
      Pugh A (n = 274), 4.775 COI (1.32-16.68) in Child-Pugh B (n = 46), and 11.37 COI
      (6.03-18.33) in Child-Pugh C (n = 18) (overall significance, P < 0.001). Serum
      M2BPGi levels showed a strong correlation with serum albumin concentration and
      controlling nutritional status score (rs  = -0.649, P < 0.001 and rs  = 0.671, P
      < 0.001, respectively). The correlations between M2BPGi and nutritional status
      markers were especially high in patients with hepatitis C virus infection and non
      B non-C hepatitis and patients with hepatocellular carcinoma. Among the three
      fibrosis markers, M2BPGi yielded the highest area under the receiver operating
      characteristic curve (0.920) for predicting hypoalbuminemia at an optimal cut-off
      value of 2.41 (sensitivity, 87.3%; specificity, 87.6%; P < 0.001). CONCLUSIONS:
      Serum M2BPGi levels are correlated with nutritional status markers in patients
      with CLD and could be a useful clinical marker of malnutrition.

PMID- 29473207
TI  - Community counts: Evolution of a national surveillance system for bleeding
      disorders.

PMID- 29473208
TI  - The perpetual state of emergency that sacrifices protected areas in a changing
      climate.
AB  - A modern challenge for conservation biology is to assess the consequences of
      policies that adhere to assumptions of stationarity (e.g., historic norms) in an
      era of global environmental change. Such policies may result in unexpected and
      surprising levels of mitigation given future climate-change trajectories,
      especially as agriculture looks to protected areas to buffer against production
      losses during periods of environmental extremes. We assessed the potential impact
      of climate-change scenarios on the rates at which grasslands enrolled in the
      Conservation Reserve Program (CRP) are authorized for emergency harvesting (i.e.,
      biomass removal) for agricultural use, which can occur when precipitation for the
      previous 4 months is below 40% of the normal or historical mean precipitation for
      that 4-month period. We developed and analyzed scenarios under the condition that
      policy will continue to operate under assumptions of stationarity, thereby
      authorizing emergency biomass harvesting solely as a function of precipitation
      departure from historic norms. Model projections showed the historical likelihood
      of authorizing emergency biomass harvesting in any given year in the northern
      Great Plains was 33.28% based on long-term weather records. Emergency biomass
      harvesting became the norm (>50% of years) in the scenario that reflected
      continued increases in emissions and a decrease in growing-season precipitation,
      and areas in the Great Plains with higher historical mean annual rainfall were
      disproportionately affected and were subject to a greater increase in emergency
      biomass removal. Emergency biomass harvesting decreased only in the scenario with
      rapid reductions in emissions. Our scenario-impact analysis indicated that
      biomass from lands enrolled in the CRP would be used primarily as a buffer for
      agriculture in an era of climatic change unless policy guidelines are adapted or
      climate-change projections significantly depart from the current consensus.

PMID- 29473209
TI  - Bendamustine-based conditioning prior to autologous stem cell transplantation
      (ASCT): Results of a French multicenter study of 474 patients from LYmphoma Study
      Association (LYSA) centers.
AB  - Carmustine shortage has led to an increase use of alternative conditioning
      regimens prior to autologous stem cell transplantation for the treatment of
      lymphoma, including Bendamustine-based (BeEAM). The aim of this study was to
      evaluate the safety of the BeEAM regimen in a large cohort of patients. A total
      of 474 patients with a median age of 56 years were analyzed. The majority of
      patients had diffuse large B-cell lymphoma (43.5%). Bendamustine was administered
      at a median dose of 197 mg/m2 /day (50-250) on days-7 and -6. The observed grade
      1-4 toxicities included mucositis (83.5%), gastroenteritis (53%), skin toxicity
      (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%), and cardiac rhythm
      disorders (4%). Nonrelapse mortality (NRM) was reported in 3.3% of patients.
      Acute renal failure (ARF) was reported in 132 cases (27.9%) (G >=2; 12.3%). Organ
      toxicities and death were more frequent in patients with post conditioning renal
      failure. In a multivariate analysis, pretransplant chronic renal failure,
      bendamustine dose >160 mg/m2 and age were independent prognostic factors for ARF.
      Pretransplant chronic renal failure, hyperhydration volume, duration of
      hyperhydration, and etoposide dose were predictive factors of NRM. A simple, four
      point scoring system can stratify patients by levels of risk for ARF and may
      allow for a reduction in the bendamustine dose to avoid toxicity. Drugs shortage
      may have dangerous consequences. Prospective, comparative studies are needed to
      confirm the toxicity/efficacy extents from this conditioning regimen compared to
      other types of high dose therapy.

PMID- 29473210
TI  - Social media mediate the education of the global microsurgeons: The experience
      from International Microsurgery Club.

PMID- 29473211
TI  - Chiroptical spectroscopy and metabolomics for blood-based sensing of pancreatic
      cancer.
AB  - To enable the early diagnosis of pancreatic cancer, the search for and definition
      of reliable biomarkers remain a subject of great interest, with the specificity
      and sensitivity of the currently used biomarkers being below the required values.
      We tested a novel diagnostic approach for pancreatic cancer based on the specific
      molecular signature of blood plasma components. To acquire more detailed
      structural information, structure-sensitive chiroptical methods (electronic
      circular dichroism and Raman optical activity) were supplemented by conventional
      Raman and infrared spectroscopies. The obtained spectra were subsequently
      processed by linear discriminant analysis yielding high values of specificity and
      sensitivity. In addition, to monitor not only large biomolecules as potential
      biomarkers but also those of low molecular weight, we conducted an analysis of
      blood plasma samples by using metabolomics. The achieved results suggest a panel
      of promising biomarkers for a reliable detection of pancreatic cancer.

PMID- 29473212
TI  - Demographic, psychosocial, and behavioral associations with cancer screening
      among a homeless population.
AB  - BACKGROUND: Although cancer incidence and mortality is declining, cancer remains
      among the leading causes of death in the United States. Research shows that
      cancer morbidity and mortality can be reduced by early detection. Yet, both
      cancer risks and screening behavior remain understudied in the homeless
      population. METHODS: Researchers conducted a cross-sectional survey of homeless
      individuals (n = 201). The analysis describes the demographic, psychosocial, and
      behavioral associations with cancer screenings and knowledge of the lung cancer
      screening recommendation. RESULTS: Participants' mean age was 51.7 years (SD
      13.6); the group was largely African American (77.3%) and male (67.9%). Among
      women, the breast and cervical cancer screening rates were 46.5% and 85.1%. Among
      men the prostate cancer screening rate was 34.2%. Among all participants, the
      colon cancer screening rate was 44%. Cancer risk behaviors were high. Lung cancer
      screening knowledge was low (23.0%). Some cancer screening behaviors were
      associated with age, income, health status, obesity, tobacco use, and physical
      activity. DISCUSSION: Despite higher cancer risk behaviors, knowledge and general
      participation rates for cancer screenings were below national benchmarks.
      CONCLUSION: To improve cancer survival among disparate populations, sustained
      community outreach is necessary to increase awareness of screening
      recommendations, identify high-risk individuals, and navigate them to resources.

PMID- 29473213
TI  - Ischemic colitis following left antegrade sclerotherapy for idiopathic
      varicocele.
AB  - The Tauber procedure, i.e., antegrade sclerotherapy for varicocele, can lead to
      ischemic colitis. The pathogenesis can involve an atypical systemic-portal
      communication, which could represent an infrequently reported (rare) anatomical
      variant. The aim of this study is to review clinical cases from the literature to
      highlight the anatomical bases of such complications. A computer-aided and hand
      checked review of the literature was used to identify relevant publications.
      Also, the computed tomography (CT) examination of a clinical case with medico
      legal implications due to severe vascular complication following Tauber's
      procedure was reviewed. Although specific references to this complication have
      appeared since the 19th century, reports in the contemporary literature include
      only a few clinical cases of ischemic colitis following Tauber's procedure. The
      CT scan images of a filed lawsuit revealed traces suggesting a significant
      communication between the testicular and left colic veins, forming part of the
      systemic-portal anastomoses. An anatomical variation consisting of a
      communication between the testicular and left colic veins has been described from
      the clinical point of view, corresponding to a significant anatomical finding
      identified in the past that has been under-reported and its clinical importance
      subsequently underestimated. For the first time we have demonstrated its
      pathophysiological significance in a real clinical scenario, linking the
      anatomical variation to the clinical complication. This demonstrates the
      importance of raising scientific awareness on this issue to prevent possibly
      devastating complications in daily clinical practice. Clin. Anat. 31:774-781,
      2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29473214
TI  - Lateral approach to the deep branch of the superficial circumflex iliac artery
      for harvesting a SCIP flap.

PMID- 29473215
TI  - Primary cutaneous aspergillosis caused by Aspergillus tamarii in a premature
      infant with extremely low birthweight: A case report with short review.
AB  - Primary cutaneous aspergillosis is a rare, life-threatening fungal infection in
      premature infants. We report a case of primary cutaneous aspergillosis caused by
      Aspergillus tamarii in an extremely low birthweight infant. The infant was
      delivered by cesarean section with complications from an intrauterine infection,
      brain intraventricular hemorrhage, tension pneumothorax and cardiac tamponade. On
      the 12th day of life, he developed erythematous maceration with erosion on his
      back. Septate hyphae were detected on two occasions from specimens of the skin
      lesion. The manifestations of the colony and slide culture showed the
      characteristics of A. tamarii. The nucleotide sequences of internal transcribed
      spacer regions of the ribosomal RNA gene, partial sequences of beta-tubulin and
      calmodulin gene were compatible with those of A. tamarii. Of the known
      Aspergillus species, Aspergillus fumigatus and Aspergillus flavus have been
      reported in previous studies as the major causative agents in primary cutaneous
      aspergillosis, whereas human infection by A. tamarii is rare. We consider that A.
      tamarii is important as an unusual opportunistic human pathogen among premature
      infants.

PMID- 29473216
TI  - Homeostatic control of dendritic cell numbers and differentiation.
AB  - Dendritic cells (DCs) are a diverse family of cells that play a crucial role in
      linking our innate and adaptive immune system to initiate adequate T-cell
      responses. They respond to pathogens by triggering the appropriate adaptive
      immune response that is required to clear invaders while balancing the need to
      limit tissue damage as a result of inflammation. Perturbation in DC regulation
      results in abnormal T-cell homeostasis, leading to development of autoimmune
      diseases and aberrant responses to pathogens. In recent years, it has become
      clear that the DC family is more complex than initially thought in terms of their
      identification, homeostasis and functions. In this review, we discuss recent
      findings that improve our understanding of development, and functional
      specializations of conventional and plasmacytoid DCs.

PMID- 29473217
TI  - A subband Steiglitz-McBride algorithm for automatic analysis of FID data.
AB  - Fast, accurate, and automatic extraction of parameters of nuclear magnetic
      resonance free induction decay (FID) signal for chemical spectroscopy is a
      challenging problem. Recently, the Steiglitz-McBride algorithm has been shown to
      exhibit superior performance in terms of speed, accuracy, and automation when
      applied to the extraction of T2 relaxation parameters for myelin water imaging of
      brain. Applying it to FID data reveals that it falls short of the second
      objective, the accuracy. Especially, it struggles with the issue of missed
      spectral peaks when applied to chemical samples with relatively dense frequency
      spectra. To overcome this issue, a preprocessing stage of subband decomposition
      is proposed before the application of Steiglitz-McBride algorithm to the FID
      signal. It is demonstrated that by doing so, a considerable improvement in
      accuracy is achieved. But this is not gained at the cost of the first objective,
      the speed. An adaptive subband decomposition is employed in conjunction with the
      Bayesian information criteria to carry out an efficient decomposition according
      to spectral content of the signal under investigation. Furthermore, adaptive
      subband decomposition and the Bayesian information criteria also serve to make
      the resulting algorithm independent of user input, which also fulfills the third
      objective, the automation. This makes the proposed algorithm favorable for fast,
      accurate, and automatic extraction of FID signal parameters.

PMID- 29473219
TI  - Soft-tissue dehiscence coverage at peri-implant sites.
AB  - Soft-tissue dehiscence at the facial aspect of an osteointegrated implant is a
      common complication which impacts on the final esthetic result. The etiology and
      ways of diagnosing this condition are still controversial. Many factors seem to
      influence the position of the peri-implant soft-tissue margin, and some of these
      have been studied more carefully than others. Various surgical and combination
      surgical-prosthetic approaches have been described to treat soft-tissue
      dehiscence, with the latter appearing to be more predictable. This paper focuses
      on the factors affecting peri-implant soft-tissue margins and describes the
      different treatment approaches, reported in the literature, to treat buccal soft
      tissue dehiscence, with more focus on the prosthetic-surgical-prosthetic
      approach.

PMID- 29473220
TI  - Cost shifting and other perverse incentives in biodiversity offsetting in India.
AB  - Biodiversity offsetting aims to compensate for development-induced biodiversity
      loss through commensurate conservation gains and is gaining traction among
      governments and businesses. However, cost shifting (i.e., diversion of offset
      funds to other conservation programs) and other perverse incentives can undermine
      the effectiveness of biodiversity offsetting. Additionality-the requirement that
      biodiversity offsets result in conservation outcomes that would not have been
      achieved otherwise-is fundamental to biodiversity offsetting. Cost shifting and
      violation of additionality can go hand in hand. India's national offsetting
      program is a case in point. Recent legislation allows the diversion of offset
      funds to meet the country's preexisting commitments under the United Nations
      Framework Convention on Climate Change (UNFCCC) and United Nations Convention on
      Biological Diversity (CBD). With such diversions, no additional conservation
      takes place and development impacts remain uncompensated. Temporary additionality
      cannot be conceded in light of paucity of funds for preexisting commitments
      unless there is open acknowledgement that fulfillment of such commitments is
      contingent on offset funds. Two other examples of perverse incentives related to
      offsetting in India are the touting of inherently neutral offsetting outcomes as
      conservation gains, a tactic that breeds false complacency and results in reduced
      incentive for additional conservation efforts, and the clearing of native
      vegetation for commercial plantations in the name of compensatory afforestation,
      a practice that leads to biodiversity decline. The risks accompanying cost
      shifting and other perverse incentives, if not preempted and addressed, will
      result in net loss of forest cover in India. We recommend accurate baselines,
      transparent accounting, and open reporting of offset outcomes to ensure
      biodiversity offsetting achieves adequate and additional compensation for impacts
      of development.

PMID- 29473218
TI  - NGF steers microglia toward a neuroprotective phenotype.
AB  - Microglia are the sentinels of the brain but a clear understanding of the factors
      that modulate their activation in physiological and pathological conditions is
      still lacking. Here we demonstrate that Nerve Growth Factor (NGF) acts on
      microglia by steering them toward a neuroprotective and anti-inflammatory
      phenotype. We show that microglial cells express functional NGF receptors in
      vitro and ex vivo. Our transcriptomic analysis reveals how, in primary microglia,
      NGF treatment leads to a modulation of motility, phagocytosis and degradation
      pathways. At the functional level, NGF induces an increase in membrane dynamics
      and macropinocytosis and, in vivo, it activates an outward rectifying current
      that appears to modulate glutamatergic neurotransmission in nearby neurons. Since
      microglia are supposed to be a major player in Abeta peptide clearance in the
      brain, we tested the effects of NGF on its phagocytosis. NGF was shown to promote
      TrkA-mediated engulfment of Abeta by microglia, and to enhance its degradation.
      Additionally, the proinflammatory activation induced by Abeta treatment is
      counteracted by the concomitant administration of NGF. Moreover, by acting
      specifically on microglia, NGF protects neurons from the Abeta-induced loss of
      dendritic spines and inhibition of long term potentiation. Finally, in an ex-vivo
      setup of acute brain slices, we observed a similar increase in Abeta engulfment
      by microglial cells under the influence of NGF. Our work substantiates a role for
      NGF in the regulation of microglial homeostatic activities and points toward this
      neurotrophin as a neuroprotective agent in Abeta accumulation pathologies, via
      its anti-inflammatory activity on microglia.

PMID- 29473221
TI  - Supplementation of broiler diets with high levels of microbial protease and
      phytase enables partial replacement of commercial soybean meal with raw, full-fat
      soybean.
AB  - A 3 * 3 + 1 factorial, involving three levels of protease (0, 15,000 or 30,000
      PROT/kg) and three levels of phytase (1,000, 2,000 or 3,000 FYT/kg), was used to
      evaluate the effect of replacing commercial soybean meal (SBM) with raw, full-fat
      soybean (RFSB) at 75 g/kg of diet for broilers. A control diet was used for
      comparison. Each treatment was replicated six times, with nine birds per
      replicate. The concentration of trypsin inhibitors (TIs) in the test diets was
      approximately 10,193.4 TIU/kg. Regardless of enzyme supplementation, feed intake
      (FI) and body weight gain (BWG) of birds in the control group were superior to
      those on the test diets. Birds that received the protease-free test diets had
      reduced FI and BWG, but when supplemented with protease, were similar to the
      control diet in BWG, FI (except 0-35 days) and feed conversion ratio (FCR). When
      the test diet was supplemented with elevated levels (extradose) of protease and
      phytase, the BWG was improved during 0-10 days (p = .05) and 0-24 days (p < .01).
      Regardless of protease supplementation, the weight of thighs was lower for birds
      fed the test diets. Birds that received the control diet had smaller weight of
      pancreas. Increasing the level of phytase supplementation reduced (p < .05) the
      weight of the pancreas. The apparent ileal digestibility (AID) of CP and AA was
      higher in birds on the control diets, but this was also improved in test diets by
      protease supplementation. The activities of trypsin (7%), general proteolytic
      (11%) and lipase (12%) were slightly increased because of protease
      supplementation. Mucosal depth and apparent villus surface areas were increased
      by about 2.9% and 20%, respectively, due to supplementation of elevated level of
      phytase. It can be concluded that RFSB could partially replace SBM in broiler
      diets, provided the diets are supplemented with elevated levels of protease and
      phytase.

PMID- 29473222
TI  - Assessing a portable, real-time display handheld meter with UV-A and UV-B sensors
      for potential application in personal sun exposure studies.
AB  - BACKGROUND: Observing accurate real-time measurements of solar ultraviolet
      radiation (UVR) levels is important since personal excess sun exposure is
      associated with skin cancers. Handheld measurement devices may be helpful but
      their accuracy is unknown. We compare a portable, science-grade solar UVR
      monitoring device against two fixed, science-grade solar UVR instruments.
      METHODS: Instruments were (1) a fixed Solar Light 501 UV-B biometer to measure UV
      B; (2) a fixed Kipp and Zonen radiometer used to measure UV-A and UV-B; and (3)
      Goldilux ultraviolet probes which are commercially available portable devices.
      Two different probes were used, one measured UV-A and the other UV-B radiation.
      The Goldilux probes were levelled and secured next to the UV-B biometer. Between
      10:00 and 14:40 UTC+2, the UV-B biometer was set to record at 10-minute intervals
      and measurements by the Goldilux probes were manually taken simultaneously.
      Results were compared for all data and by solar zenith angle (SZA) ranges.
      RESULTS: The Goldilux UV-B probe measured UV-B relatively well in its diurnal
      pattern, however, its readings were ~77% higher than those made by the UV-B
      biometer. While UV-A measurements from the Goldilux UV-A probe and those from the
      radiometer were in relatively good agreement in pattern, the radiometer read ~47%
      higher than the Goldilux UV-A probe. UV-B data from Goldilux UV-B probe had a
      moderately strong correlation with UV-B biometer data for small SZAs; conversely,
      for UV-A, the Goldilux UV-A probe had a strong correlation with the UV-A
      radiometer data for large SZAs. CONCLUSION: Handheld devices may be useful to
      provide real-time readings of solar UVR patterns, however, to achieve
      synchronicity in the magnitude of readings to those made by science-grade fixed
      instruments, devices may need to be used during certain times of the day and in
      clear-sky conditions which may not be practical in personal exposure studies.

PMID- 29473223
TI  - Epicrestal and subcrestal placement of platform-switched implants: 18 month
      result of a randomized, controlled, split-mouth, prospective clinical trial.
AB  - OBJECTIVES: To evaluate the changes in marginal bone levels (MBL) and soft tissue
      dimension around platform-switched implants with the implant-abutment junction
      (IAJ) placed at the crest or 1.5-2 mm subcrestally. MATERIALS AND METHODS: In
      all, 96 platform-switched implants were placed in either the posterior maxilla or
      mandible in 48 partially edentulous patients in a split-mouth study. All implants
      were provisionally restored after 4-5 months and definitively after 6 months
      (T6). Radiographic assessment of MBL was assessed at implant placement (T0), T6,
      12 months (T12), and 18 months (T18) after placement. Mid-buccal soft tissue and
      papilla measurements were performed at T6, T12, and T18. RESULTS: In all, 43
      patients with 86 implants completed the study. The T18 examination showed an
      implant survival rate of 100% in both groups. Analysis showed that MBL varied as
      a function of IAJ location, which indicated more coronal bone levels with
      subcrestal (2.39 +/- 0.08 mm) than with epicrestal placements (0.88 +/- 0.08 mm)
      (p < .05). Greater average marginal bone loss was found in the subcrestal group
      (0.40 +/- 0.07 mm) compared to the epicrestal group (0.13 +/- 0.08 mm) although
      no statistically significant difference was found at T18 (p > .05). Levels of mid
      buccal soft tissue had no significant changes over time, regardless of group (p >
      .05). There was a significant difference in increase in papilla between T6 and
      T12 and T18 (p = .005 and .001), but not between T12 and T18 (p = .61). These
      papilla levels and changes were similar between groups (p > .05). CONCLUSIONS:
      The MBL changes around platform-switched implants with same geometry were not
      affected by the epicrestal or subcrestal location of the IAJ. Furthermore, the
      location of the IAJ did not affect the implant survival and soft tissue
      dimensions. However, no bone loss was located apical to the IAJ when the implants
      were placed subcrestally.

PMID- 29473224
TI  - What's in a giant cell? A case of metastatic sarcomatoid pleomorphic carcinoma
      with osteoclast-like giant cells involving the thyroid.

PMID- 29473225
TI  - High-Nuclearity Heterometallic tert-Butylethynide Clusters Assembled with tert
      Butylphosphonate.
AB  - tert-Butylphosphonic acid and lanthanide precursors were employed to construct
      two high-nuclearity hybrid silver(I)-ytterbium(III) phosphonate clusters:
      compound 1 consists of a Ag16 ethynide cluster fused with a trinuclear
      hydroxoytterbium phosphonate cluster, whereas compound 2 is composed of two Ag16
      ethynide clusters bridged by a hexanuclear oxo/hydroxoytterbium phosphonate
      cluster. Using transition-metal-substituted lacunary polyoxotungstates in place
      of the lanthanide reactant, new phosphonate-functionalized silver(I)-copper(II)
      ethynide clusters [Ag34 Cu6 (3) and Ag37 Cu6 (4)] and silver(I) ethynide clusters
      [Ag51 (5) and Ag72 (6)] were obtained. The structures of complexes 3-6 feature
      core-shell arrangements, in which silver(I)-copper(II) or silver(I) ethynide
      cluster shells stabilized by peripheral phosphonate ligands enclose different
      kinds of tungstate core templates.

PMID- 29473226
TI  - Infiltrative lamina propria invasion pattern as an independent predictor for
      cancer-specific and overall survival of instillation treatment-naive stage T1
      high-grade urothelial bladder cancer.
AB  - OBJECTIVES: To investigate established prognostic factors and relatively new
      histopathological tumor characteristics including metric substage and lamina
      propria invasion patterns in a large series of T1 high-grade non-muscle-invasive
      bladder cancer. METHODS: Between 1989 and 2012, 322 patients with initial stage
      T1 high-grade bladder cancer underwent transurethral resection, followed by re
      transurethral resection and a conservative approach with follow-up regime alone
      or instillation treatment. Transurethral resection specimens were reassessed by
      two experienced urological pathologists for tumor grade according to the World
      Health Organization 1973 classification, metric T1 substage, lamina propria
      invasion pattern and associated carcinoma in situ. The median follow-up period
      was 42 months (interquartile range 25-72 months). In addition to Kaplan-Meier
      analyses, uni- and multivariable Cox regression analyses were used to compare
      progression-free survival, cancer-specific survival and overall survival for the
      studied parameters comparing two subcohorts. RESULTS: While in patients after
      instillation treatment no examined feature was shown as an independent predictor
      for prognosis, there were predictive histopathological features in multivariable
      Cox regression analyses in instillation treatment-naive patients: associated
      carcinoma in situ (hazard ratio 2.278, 95% confidence interval 1.119-4.634, P =
      0.023) and World Health Organization 1973 grade 3 (hazard ratio 2.950, 95%
      confidence interval 1.021-8.536, P = 0.046) for worse progression-free survival,
      infiltrative lamina propria tumor pattern for worse cancer-specific survival
      (hazard ratio 2.369, 95% confidence interval 1.034-5.429, P = 0.042) and overall
      survival (hazard ratio 1.049, 95% confidence interval 1.024-1.075, P = 0.001).
      CONCLUSIONS: The results of the present T1 high-grade bladder cancer series
      suggest that lamina propria invasion pattern is a promising parameter to predict
      the prognosis of T1 high-grade bladder cancer in an instillation treatment-naive
      subcohort. Prospective multicenter evaluations are warranted. The need for
      instillation treatment in T1 high-grade bladder cancer is clearly demanded.

PMID- 29473227
TI  - Amorphizing of Cu Nanoparticles toward Highly Efficient and Robust
      Electrocatalyst for CO2 Reduction to Liquid Fuels with High Faradaic
      Efficiencies.
AB  - Conversion of carbon dioxide (CO2 ) into valuable chemicals, especially liquid
      fuels, through electrochemical reduction driven by sustainable energy sources, is
      a promising way to get rid of dependence on fossil fuels, wherein developing of
      highly efficient catalyst is still of paramount importance. In this study, as a
      proof-of-concept experiment, first a facile while very effective protocol is
      proposed to synthesize amorphous Cu NPs. Unexpectedly, superior electrochemical
      performances, including high catalytic activity and selectivity of CO2 reduction
      to liquid fuels are achieved, that is, a total Faradaic efficiency of liquid
      fuels can sum up to the maximum value of 59% at -1.4 V, with formic acid (HCOOH)
      and ethanol (C2 H6 O) account for 37% and 22%, respectively, as well as a
      desirable long-term stability even up to 12 h. More importantly, this work opens
      a new avenue for improved electroreduction of CO2 based on amorphous metal
      catalysts.

PMID- 29473228
TI  - Evaluating methods for extraction of alpha-cellulose from leaves of Melaleuca
      quinquenervia for stable carbon and oxygen isotope analysis.
AB  - RATIONALE: Purification of alpha-cellulose from plant tissues is commonly
      conducted to facilitate the reliable measurement of stable isotope ratios. Prior
      research has shown that different plant species and tissues react differently to
      standardised cellulose extraction techniques. Thus, no single method can be
      applied to all materials and careful consideration must be undertaken when
      selecting an extraction technique. METHODS: In order to evaluate their
      suitability for use on Melaleuca quinquenervia leaves, a suite of eight different
      cellulose extraction techniques were tested. Leaves of this species are preserved
      in perched lakes on southeast Queensland's sand islands and are a focus of
      ongoing palaeoclimate research. Elemental analyser/isotope ratio mass
      spectrometry was used to measure stable carbon and oxygen isotopic ratios and
      sample composition was measured using Fourier transform infrared spectroscopy.
      RESULTS: We demonstrate that the standard Brendel extraction technique,
      particularly with a higher reagent volume and longer boiling time, produces
      cellulose with the lowest spread in isotopic ratios among replicates, and with
      the fewest impurities detected by Fourier transform infrared spectroscopy. We
      also show that pre-treating the leaves to extract leaf wax lipids in order to
      enable paired analysis from the same sub-fossil leaves does not significantly
      affect the quality of the isotopic results. CONCLUSIONS: The standard Brendel
      method allows the most precise stable carbon and oxygen information to be
      retrieved from the leaves of M. quinquenervia. This unlocks the potential to
      study palaeoclimate proxy records from our study site and potentially throughout
      the natural range of the species across eastern Australia, Papua New Guinea and
      New Caledonia.

PMID- 29473229
TI  - Follicular fluid stimulates capacitation and acrosome reaction in alpaca sperm
      (Vicugna pacos).
AB  - The follicular fluid exerts an effect on the sperm capacitation of several
      species; however, these effects vary according to species, both in the sperm
      motility and in the subsequent acrosome reaction. In this study, the effect of
      alpaca follicular fluid (aFF) on the motility and acrosome reaction of alpaca
      spermatozoa was observed, using follicular fluid of three follicle sizes: small
      (<3 mm), medium (3-6 mm) and large (>6 mm), in a concentration of 30%. Sperm
      motility at the first hour of incubation with aFF of small follicles was 48.0%,
      with aFF of medium follicles it was 43.33% and with aFF of large follicles, it
      was 34.53%, while control averaged 26.00%. At the second hour, control achieved
      an average of 28.13%, treatment with aFF from small follicles showed an average
      of 46.53%, with aFF from medium follicles it was 40.00% and with aFF from large
      follicles it was 35.60%. The acrosome reaction after 4 hours of incubation was
      30.06% for control, whereas for aFF of small follicles it was 66.3%, with aFF of
      medium follicles it was 58.86% and for aFF of large follicles, it was 67.63%. In
      the case of sperm motility, a significant difference is demonstrated for all
      treatments in relation to the control at the first hour, whereas only the
      treatments with aFF of small and medium follicles show a significant difference
      with respect to the control at the second hour. In the case of the acrosome
      reaction, all treatments with follicular fluid show a significant difference with
      respect to the control. It was concluded that alpaca follicular fluid favours
      sperm capacitation and the acrosome reaction in alpaca spermatozoa.

PMID- 29473231
TI  - Quantum Emitters in Hexagonal Boron Nitride Have Spectrally Tunable Quantum
      Efficiency.
AB  - Understanding the properties of novel solid-state quantum emitters is pivotal for
      a variety of applications in research fields ranging from quantum optics to
      biology. Recently discovered defects in hexagonal boron nitride are especially
      interesting, as they offer much desired characteristics such as narrow emission
      lines and photostability. Here, the dependence of the emission on the excitation
      wavelength is studied. It is found that, in order to achieve bright single-photon
      emission with high quantum efficiency, the excitation wavelength has to be
      matched to the emitter. This is a strong indication that the emitters possess a
      complex level scheme and cannot be described by a simple two or three-level
      system. Using this excitation dependence of the emission, further insight to the
      internal level scheme is gained and it is demonstrated how to distinguish
      different emitters both spatially as well as in terms of their photon
      correlations.

PMID- 29473230
TI  - Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy.
AB  - Extracellular vesicles (EVs) have recently gained significant attention as
      important mediators of intercellular communication, potential drug carriers, and
      disease biomarkers. These natural cell-derived nanoparticles are postulated to be
      biocompatible, stable under physiological conditions, and to show reduced
      immunogenicity as compared to other synthetic nanoparticles. Although initial
      clinical trials are ongoing, the use of EVs for therapeutic applications may be
      limited due to undesired off-target activity and potential "dilution effects"
      upon systemic administration which may affect their ability to reach their target
      tissues. To fully exploit their therapeutic potential, EVs are embedded into
      implantable biomaterials designed to achieve local delivery of therapeutics
      taking advantage of enzyme prodrug therapy (EPT). In this first application of
      EVs for an EPT approach, EVs are used as smart carriers for stabilizing enzymes
      in a hydrogel for local controlled conversion of benign prodrugs to active
      antiinflammatory compounds. It is shown that the natural EVs' antiinflammatory
      potential is comparable or superior to synthetic carriers, in particular upon
      repeated long-term incubations and in different macrophage models of
      inflammation. Moreover, density-dependent color scanning electron microscopy
      imaging of EVs in a hydrogel is presented herein, an impactful tool for further
      understanding EVs in biological settings.

PMID- 29473232
TI  - Spacer Length-Independent Shuttling of the Pillar[5]arene Ring in Neutral
      [2]Rotaxanes.
AB  - For a series of neutral [2]rotaxanes consisting of a pillar[5]arene ring and
      axles possessing two stations separated by flexible spacers of different lengths,
      the free energies of activation for the ring shuttling between the stations were
      found to be independent of the spacer length. The constitution of the spacer
      affects the activation energies: replacement of CH2 groups by repulsive oxygen
      atoms in the axle increases the barrier. The explanation for the observed length
      independence lies in the presence of a barrier for re-forming the stable co
      conformation, which makes the ring travel back and forth along the thread in an
      intermediate state.

PMID- 29473233
TI  - Highly Augmented Drug Loading and Stability of Micellar Nanocomplexes Composed of
      Doxorubicin and Poly(ethylene glycol)-Green Tea Catechin Conjugate for Cancer
      Therapy.
AB  - Low drug loading and instability in blood circulation are two key challenges that
      impede the successful clinical translation of nanomedicine, as they result in
      only marginal therapeutic efficacy and toxic side effects associated with
      premature drug leakage, respectively. Herein, highly stable and ultrahigh drug
      loading micellar nanocomplexes (MNCs) based on the self-assembly of the
      anticancer drug doxorubicin (DOX) and a poly(ethylene glycol)-epigallocatechin-3
      O-gallate (EGCG) conjugate are developed. The formation of these MNCs is
      facilitated by strong favorable intermolecular interactions between the
      structurally similar aromatic EGCG and DOX molecules, which impart exceptionally
      high drug-loading capability of up to 88% and excellent thermodynamic and kinetic
      stability. Unlike two clinical formulations of DOX-free DOX and liposomal DOX,
      which are not effective below their lethal dosages, these DOX-loaded MNCs
      demonstrate significant tumor growth inhibition in vivo on a human liver cancer
      xenograft mouse model with minimal unwanted toxicity. Overall, these MNCs can
      represent a safe and effective strategy to deliver DOX for cancer therapy.

PMID- 29473234
TI  - Direct Growth of Highly Stable Patterned Graphene on Dielectric Insulators using
      a Surface-Adhered Solid Carbon Source.
AB  - A novel method is described for the direct growth of patterned graphene on
      dielectric substrates by chemical vapor deposition (CVD) in the presence of Cu
      vapor and using a solid aromatic carbon source, 1,2,3,4-tetraphenylnapthalene
      (TPN), as the precursor. The UV/O3 treatment of the TPN film both crosslinks TPN
      and results in a strong interaction between the substrate and the TPN that
      prevents complete sublimation of the carbon source from the substrate during CVD.
      Substrate-adhered crosslinked TPN is successfully converted to graphene on the
      substrate without any organic contamination. The graphene synthesized by this
      method shows excellent mechanical and chemical stability. This process also
      enables the simultaneous patterning of graphene materials, which can thus be used
      as transparent electrodes for electronic devices. The proposed method for the
      synthesis directly on substrates of patterned graphene is expected to have wide
      applications in organic and soft hybrid electronics.

PMID- 29473236
TI  - Oxide Thin-Film Electronics using All-MXene Electrical Contacts.
AB  - 2D MXenes have shown great promise in electrochemical and electromagnetic
      shielding applications. However, their potential use in electronic devices is
      significantly less explored. The unique combination of metallic conductivity and
      hydrophilic surface suggests that MXenes can also be promising in electronics and
      sensing applications. Here, it is shown that metallic Ti3 C2 MXene with work
      function of 4.60 eV can make good electrical contact with both zinc oxide (ZnO)
      and tin monoxide (SnO) semiconductors, with negligible band offsets.
      Consequently, both n-type ZnO and p-type SnO thin-film transistors (TFTs) have
      been fabricated entirely using large-area MXene (Ti3 C2 ) electrical contacts,
      including gate, source, and drain. The n- and p-type TFTs show balanced
      performance, including field-effect mobilities of 2.61 and 2.01 cm2 V-1 s-1 and
      switching ratios of 3.6 * 106 and 1.1 * 103 , respectively. Further,
      complementary metal oxide semiconductor (CMOS) inverters are demonstrated. The
      CMOS inverters show large voltage gain of 80 and excellent noise margin of 3.54
      V, which is 70.8% of the ideal value. Moreover, the operation of CMOS inverters
      is shown to be very stable under a 100 Hz square waveform input. The current
      results suggest that MXene (Ti3 C2 ) can play an important role as contact
      material in nanoelectronics.

PMID- 29473235
TI  - Caveolin 3-dependent loss of t-tubular ICa during hypertrophy and heart failure
      in mice.
AB  - NEW FINDINGS: What is the central question of this study? Heart failure is
      associated with redistribution of L-type Ca2+ current (ICa ) away from the t
      tubule membrane to the surface membrane of cardiac ventricular myocytes. However,
      the underlying mechanism and its dependence on severity of pathology (hypertrophy
      versus failure) are unclear. What is the main finding and its importance?
      Increasing severity of response to transverse aortic constriction, from
      hypertrophy to failure, was accompanied by graded loss of t-tubular ICa and loss
      of regulation of ICa by caveolin 3. Thus, the pathological loss of t-tubular ICa
      , which contributes to impaired excitation-contraction coupling and thereby
      cardiac function in vivo, appears to be attributable to loss of caveolin 3
      dependent stimulation of t-tubular ICa . ABSTRACT: Previous work has shown
      redistribution of L-type Ca2+ current (ICa ) from the t-tubules to the surface
      membrane of rat ventricular myocytes after myocardial infarction. However,
      whether this occurs in all species and in response to other insults, the
      relationship of this redistribution to the severity of the pathology, and the
      underlying mechanism, are unknown. We have therefore investigated the response of
      mouse hearts and myocytes to pressure overload induced by transverse aortic
      constriction (TAC). Male C57BL/6 mice underwent TAC or equivalent sham operation
      8 weeks before use. ICa and Ca2+ transients were measured in isolated myocytes,
      and expression of caveolin 3 (Cav3), junctophilin 2 (Jph2) and bridging
      integrator 1 (Bin1) was determined. C3SD peptide was used to disrupt Cav3 binding
      to its protein partners. Some animals showed cardiac hypertrophy in response to
      TAC with little evidence of heart failure, whereas others showed greater
      hypertrophy and pulmonary congestion. These graded changes were accompanied by
      graded cellular hypertrophy, t-tubule disruption, decreased expression of Jph2
      and Cav3, and decreased t-tubular ICa density, with no change at the cell
      surface, and graded impairment of Ca2+ release at t-tubules. C3SD decreased ICa
      density in control but not in TAC myocytes. These data suggest that the graded
      changes in cardiac function and size that occur in response to TAC are paralleled
      by graded changes in cell structure and function, which will contribute to the
      impaired function observed in vivo. They also suggest that loss of t-tubular ICa
      is attributable to loss of Cav3-dependent stimulation of ICa .

PMID- 29473237
TI  - Dietary outcomes of overweight fathers and their children in the Healthy Dads,
      Healthy Kids community randomised controlled trial.
AB  - BACKGROUND: Few studies have examined dietary intake changes following a weight
      loss intervention in fathers and the association between father-child dietary
      intakes. The present study aimed to: (i) evaluate the change in dietary intake in
      overweight fathers randomised to a family-based lifestyle intervention [Healthy
      Dads Healthy Kids (HDHK)] versus controls and (ii) investigate whether an
      association exists between father-child dietary intakes. METHODS: A secondary
      analysis was conducted of father-child baseline and 3-month post-intervention
      data (n = 93) collected in the HDHK community randomised controlled trial.
      Intention-to-treat linear mixed models were used to assess dietary changes by
      group, time (baseline and 3-month) and the group-by-time interaction. Cohens d
      was used to determine effect sizes. RESULTS: Significant group-by-time effects
      (all P < 0.05) favouring fathers in the intervention group were identified for
      total daily energy intake (-1956 kJ, d = 0.74), total sugars (-45 g, d = 0.63),
      sodium (-414 mg, d = 0.58) and % energy from nutrient-dense, core foods (+10.1%,
      d = 0.86), fruit (+2.4%, d = 0.71), vegetarian protein sources (+1.2%, d = 0.57),
      pre-packed snacks (+1.7%, d = 0.58) and sugar-sweetened beverages (-4.1%, d =
      0.58). At baseline, positive correlations were observed between father-child
      intakes for a number of dietary variables, and significant correlations were
      observed between father-child change scores for % energy carbohydrate (r = 0.35,
      P = 0.023), % energy from fruit (r = 0.47, P = 0.002), vegetarian protein sources
      (r = 0.46, P = 0.002) and frequency of consuming meals with vegetables (r = 0.38,
      P = 0.012). CONCLUSIONS: The HDHK intervention successfully improved some aspects
      of father's dietary intakes compared to controls. The fathers' eating patterns
      also correlated with those of their children for several dietary variables. These
      novel data suggest that fathers can be targeted as agents of dietary change
      within obesity prevention and treatment programmes.

PMID- 29473238
TI  - eHealth readiness of dietitians.
AB  - BACKGROUND: The present study aimed to determine the eHealth readiness and
      changes over time of dietitians in Australia. METHODS: Two cross-sectional
      analyses of Australian dietitians were conducted in 2013 and 2016, using a survey
      adapted from one conducted in 2011 by the US Academy of Nutrition and Dietetics.
      The survey encompassed 30 questions on eHealth readiness across five dimensions:
      access, standards, attitude, aptitude and advocacy. Descriptive statistics,
      independent t-tests, chi-squared tests and Z-tests were computed to compare
      responses from the 2013 and 2016 surveys. RESULTS: The survey completion rate
      represented 14.5% (747) of the Dietitians Association of Australia members in
      2013 and 8% (417) in 2016. The survey responses in relation to access and
      standards suggest that dietitians are well positioned for eHealth. For attitude
      and aptitude, there is a moderate level of preparedness, with minor improvements
      over time. Although showing significant improvement (P < 0.05), advocacy
      highlights the area requiring the most development because the majority of
      dietitians (61%) reported 'no role' in eHealth solutions. CONCLUSIONS: Dietitians
      are progressing in relation to access, attitudinal and aptitudinal readiness for
      eHealth, although they rate poorly with respect to advocacy readiness. It was
      concluded that dietitians are not yet ready, and also that valuable opportunities
      to achieve the benefits that eHealth can deliver will be missed, if dietitians do
      not take the lead in guiding the development, selection and implementation of
      nutrition-related technologies. Strengthening the dimension of advocacy and
      ensuring collaboration across the profession, drawing on the varying expertise
      demonstrated across the practice areas and by the different generations, will be
      central to improving dietitian eHealth readiness.

PMID- 29473239
TI  - Managed alcohol programs: Is it time for a more radical approach to reduce harms
      for people experiencing homelessness and alcohol use disorders?

PMID- 29473240
TI  - Loss of PPM1F expression predicts tumour recurrence and is negatively regulated
      by miR-590-3p in gastric cancer.
AB  - OBJECTIVES: MicroRNAs (miRNAs) as small non-coding RNA molecules act by
      negatively regulating their target genes. Recent studies have shown that protein
      phosphatase Mg2+/Mn2+-dependent 1F (PPM1F) plays a critical role in cancer
      metastasis. But, the regulation mechanisms of PPM1F by miRNAs in gastric cancer
      (GC) remain undefined. METHODS: The correlation of PPM1F or miR-590-3p (miR-590)
      expression with clinicopathological features and prognosis of the patients with
      GC was analysed by TCGA RNA-sequencing data. The miRNAs that target PPM1F gene
      were identified by bioinformatics and Spearman correlation analysis, and the
      binding site between miR-590 and PPM1F 3'UTR was confirmed by dual luciferase
      assay. MTT and Transwell assays were conducted to evaluate the effects of miR-590
      or (and) PPM1F on cell proliferation and invasion. RESULTS: We found that PPM1F
      expression was downregulated in GC tissues and cell lines and was correlated with
      tumour recurrence in patients with GC. The decreased expression of PPM1F was
      attributed to the dysregulation of miR-590 expression rather than its genetic or
      epigenetic alterations. Overexpression of miR-590 promoted cell proliferation and
      invasion capability of GC cells, while knockdown of miR-590 reversed these
      effects. Moreover, PPM1F was validated as a direct target of miR-590 and
      counteracted the tumour-promoting effects caused by miR-590. The expression of
      miR-590 presented the negative correlation with PPM1F expression and acted as an
      independent prognostic factor for tumour recurrence in patients with GC.
      CONCLUSION: PPM1F may function as a suppressive factor and is negatively
      regulated by miR-590 in GC.

PMID- 29473242
TI  - The genomic footprint of climate adaptation in Chironomus riparius.
AB  - The gradual heterogeneity of climatic factors poses varying selection pressures
      across geographic distances that leave signatures of clinal variation in the
      genome. Separating signatures of clinal adaptation from signatures of other
      evolutionary forces, such as demographic processes, genetic drift and adaptation,
      to nonclinal conditions of the immediate local environment is a major challenge.
      Here, we examine climate adaptation in five natural populations of the harlequin
      fly Chironomus riparius sampled along a climatic gradient across Europe. Our
      study integrates experimental data, individual genome resequencing, Pool-Seq data
      and population genetic modelling. Common-garden experiments revealed
      significantly different population growth rates at test temperatures
      corresponding to the population origin along the climate gradient, suggesting
      thermal adaptation on the phenotypic level. Based on a population genomic
      analysis, we derived empirical estimates of historical demography and migration.
      We used an FST outlier approach to infer positive selection across the climate
      gradient, in combination with an environmental association analysis. In total, we
      identified 162 candidate genes as genomic basis of climate adaptation. Enriched
      functions among these candidate genes involved the apoptotic process and
      molecular response to heat, as well as functions identified in studies of climate
      adaptation in other insects. Our results show that local climate conditions
      impose strong selection pressures and lead to genomic adaptation despite strong
      gene flow. Moreover, these results imply that selection to different climatic
      conditions seems to converge on a functional level, at least between different
      insect species.

PMID- 29473241
TI  - Immunohistochemical assessment of Survivin and Bcl3 expression as potential
      biomarkers for NF-kappaB activation in the Barrett metaplasia-dysplasia
      adenocarcinoma sequence.
AB  - Non-dysplastic Barrett's oesophagus (NDBE) occurs as a consequence of an
      inflammatory response triggered through prolonged gastro-oesophageal reflux and
      it may precede the development of oesophageal adenocarcinoma. NF-kappaB
      activation as a result of the inflammatory response has been shown in NDBE, but
      the possible mechanism involved in the process is unknown. The aim of this study
      was to assess, using immunohistochemistry, Survivin and Bcl3 expression as
      potential biomarkers for NF-kappaB activation along the oesophageal metaplasia
      dysplasia-adenocarcinoma sequence. Survivin is an NF-kappaB-inducible anti
      apoptotic protein, and Bcl3 is a negative regulator of NF-kappaB. There was
      progressive upregulation of Survivin expression along the oesophageal metaplasia
      dysplasia-adenocarcinoma sequence. Bcl3 expression was upregulated in non
      dysplastic Barrett's oesophagus, low-grade, high-grade dysplasia and oesophageal
      adenocarcinoma when compared to squamous group. The study shows the differential
      expression of Bcl3 between the squamous and Barrett's stage, suggesting that Bcl3
      could be a surrogate marker for early event involving constitutive NF-kappaB
      activation. In addition, the study suggests that NF-kappaB activation may infer
      resistance to apoptosis through the expression of anti-apoptotic genes such as
      Survivin, which showed progressive increase in expression throughout the
      oesophageal metaplasia-dysplasia-adenocarcinoma sequence. This ability to avoid
      apoptosis may underlie the persistence and malignant predisposition of Barrett's
      metaplasia.

PMID- 29473243
TI  - Development and validation of an algorithm for the study of sleep using a
      biometric shirt in young healthy adults.
AB  - Portable polysomnography is often too complex and encumbering for recording sleep
      at home. We recorded sleep using a biometric shirt (electrocardiogram sensors,
      respiratory inductance plethysmography bands and an accelerometer) in 21 healthy
      young adults recorded in a sleep laboratory for two consecutive nights, together
      with standard polysomnography. Polysomnographic recordings were scored using
      standard methods. An algorithm was developed to classify the biometric shirt
      recordings into rapid eye movement sleep, non-rapid eye movement sleep and wake.
      The algorithm was based on breathing rate and heart rate variability, body
      movement, and included a correction for sleep onset and offset. The overall mean
      percentage of agreement between the two sets of recordings was 77.4%; when non
      rapid eye movement and rapid eye movement sleep epochs were grouped together, it
      increased to 90.8%. The overall kappa coefficient was 0.53. Five of the seven
      sleep variables were significantly correlated. The findings of this pilot study
      indicate that this simple portable system could be used to estimate the general
      sleep pattern of young healthy adults.

PMID- 29473244
TI  - The increased trend of non-drinking in adolescence: The role of parental
      monitoring and attitudes toward offspring drinking.
AB  - INTRODUCTIONS AND AIMS: The proportion of adolescents who do not drink alcohol
      has increased during the last decade in many European countries, the USA and
      Australia. Few studies have addressed why this positive trend has occurred. The
      aim of the present study is to examine associations between parenting factors,
      peers' alcohol use and non-drinking among 15- to 16-year-old adolescents over
      time, from 2003 to 2015, and to evaluate potential gender differences. DESIGN AND
      METHODS: Data from the Swedish subsample of European School Survey Project on
      Alcohol and Other Drugs were used. Data were available for 2003, 2007, 2011 and
      2015 in nation-based samples with responses from 11 531 adolescents in total.
      RESULTS: The proportion of non-drinkers increased from 23.2% in 2003 to 48.7% in
      2015. For each year, indicators of especially restrictive attitudes toward
      offspring drinking were robustly associated with an increased probability of non
      drinking. However, neither indicators of parental monitoring nor parental
      attitudes toward offspring drinking were associated with the increase in the
      proportion of non-drinkers that occurred from 2003 to 2015. Two indicators of
      parental monitoring were more strongly associated with non-drinking among girls
      than among boys, while paternal restrictive attitudes toward offspring drinking
      were more strongly associated with non-drinking among boys than girls. DISCUSSION
      AND CONCLUSIONS: Parenting characteristics are important for adolescents who do
      not use alcohol, which has implications for prevention strategies. However, the
      increased trend of non-drinkers could not be attributed to parental factors.

PMID- 29473245
TI  - Does training people to administer take-home naloxone increase their knowledge?
      Evidence from Australian programs.
AB  - INTRODUCTION AND AIMS: Take-home naloxone (THN) programs have been operating in
      Australia since 2012 in a variety of settings. We examine whether THN programs
      were effective in increasing knowledge about opioid overdose and appropriate
      responses in program participants. DESIGN AND METHODS: Data were obtained from
      pre- and post-training questionnaires administered as part of the early
      evaluations of THN naloxone programs operated in Sydney (n = 67), Melbourne (n =
      280), Perth (n = 153) and Canberra (n = 183). Pooled data from comparable items,
      analysed in the domains specified in previously-developed evaluation scales, were
      compared using repeated-measures analysis of variance and random effects logistic
      regression. Results pre- and post-training were compared as well as results
      across sites. RESULTS: High levels of knowledge about overdose risks and signs
      and appropriate actions to take were observed at baseline and this generally
      improved over time. No substantial differences were identified across cities.
      Knowledge also increased with participant age but the improvements over time were
      similar in each age group. There were small differences by participant gender
      with knowledge generally higher among females. DISCUSSION AND CONCLUSIONS: THN
      programs are effective in improving knowledge related to overdose response. Major
      improvements in knowledge were limited to overdose recognition and effect of
      naloxone suggesting that education may best be focused on overdose signs and the
      use of naloxone among populations accessed through these programs. A focus on
      younger people also appears warranted. Further work is needed to understand the
      impact of training and knowledge on actual behaviours around overdose events.

PMID- 29473246
TI  - Variant pathogenicity evaluation in the community-driven Inherited Neuropathy
      Variant Browser.
AB  - Charcot-Marie-Tooth disease (CMT) is an umbrella term for inherited neuropathies
      affecting an estimated one in 2,500 people. Over 120 CMT and related genes have
      been identified and clinical gene panels often contain more than 100 genes. Such
      a large genomic space will invariantly yield variants of uncertain clinical
      significance (VUS) in nearly any person tested. This rise in number of VUS
      creates major challenges for genetic counseling. Additionally, fewer individual
      variants in known genes are being published as the academic merit is decreasing,
      and most testing now happens in clinical laboratories, which typically do not
      correlate their variants with clinical phenotypes. For CMT, we aim to encourage
      and facilitate the global capture of variant data to gain a large collection of
      alleles in CMT genes, ideally in conjunction with phenotypic information. The
      Inherited Neuropathy Variant Browser provides user-friendly open access to
      currently reported variation in CMT genes. Geneticists, physicians, and genetic
      counselors can enter variants detected by clinical tests or in research studies
      in addition to genetic variation gathered from published literature, which are
      then submitted to ClinVar biannually. Active participation of the broader CMT
      community will provide an advance over existing resources for interpretation of
      CMT genetic variation.

PMID- 29473247
TI  - Double-blind placebo-controlled multicenter phase II trial to evaluate D
      methionine in preventing/reducing oral mucositis induced by radiation and
      chemotherapy for head and neck cancer.
AB  - BACKGROUND: The purpose of this study was to test if oral D-methionine (D-met)
      reduced mucositis during chemoradiotherapy. METHODS: We conducted a placebo
      controlled double-blind randomized phase II trial of D-met (100 mg/kg p.o.
      b.i.d.) testing the rate of severe (grades 3-4) mucositis. RESULTS: Sixty
      patients were randomized. Grade 2 + oral pain was higher with placebo (79% vs
      45%; P = .0165), whereas grade 2 + body odor was greater with D-met (3% vs 41%; P
      = .0015). Mucositis was decreased with D-met by the physician (World Health
      Organization [WHO], P = .007; Radiation Therapy Oncology Group [RTOG], P = .009)
      and patient functional scales (RTOG, P = .0023). The primary end point of grades
      3 to 4 mucositis on the composite scale demonstrated a decrease with D-met (48%
      vs 24%; P = .058), which was borderline in significance. A planned secondary
      analysis of a semiquantitative scoring system noted decreased oral ulceration
      (2.2 vs 1.5; P = .023) and erythema (1.6 vs 1.1; P = .048) with D-met.
      CONCLUSION: Although not meeting the primary end point, results of multiple
      assessments suggest that D-met decreased mucositis.

PMID- 29473248
TI  - Posttraumatic growth in head and neck cancer survivors: Is it possible and what
      are the correlates?
AB  - OBJECTIVES: Posttraumatic growth (PTG) is a possible positive consequence of a
      traumatic event, such as cancer. Head and neck cancer (HNC) may be particularly
      traumatic, given its adverse effects on functional, psychological, and social
      wellbeing. We investigated the extent of PTG, factors associated with PTG, and
      associations between PTG and health-related quality-of-life (HRQoL) in HNC
      survivors. METHODS: HNC survivors (ICD10 C00-C14, C32), identified from the
      population-based National Cancer Registry Ireland, completed a postal survey. PTG
      was assessed using the Posttraumatic Growth Inventory (PTG-I) and HRQoL with FACT
      G and FACT-H&N. Associations between socio-economic characteristics, social
      support, and clinical variables and PTG were examined using multivariable linear
      regression. Total HRQoL scores were compared in those with none-low PTG vs
      moderate-high PTG. RESULTS: A total of 583 survivors participated (response rate
      = 59%). The mean PTG score was 55.74 (95%CI 53.15-58.33); 60% had moderate-high
      PTG. Survivors scored highest in the PTG-I domain appreciation of life. In
      multivariable analysis, being female, being younger, having more social support,
      and having cancer-related financial stress were significantly associated with
      more PTG. HRQoL was significantly higher in those with moderate-high than no
      little PTG (P < .01). CONCLUSIONS: A notable proportion of HNC survivors report
      PTG but growth is, on average, lower than reported for other cancers.
      Nonetheless, higher PTG appears related to better HRQoL. Further research would
      be valuable to understand the pathways by which HNC may lead to PTG and inform
      development of strategies to support and encourage PTG in this survivor
      population.

PMID- 29473249
TI  - Immune checkpoint inhibitors in cancer therapy: a focus on T-regulatory cells, by
      Varun Sasidharan Nair and Eyad Elkord (Erratum).

PMID- 29473250
TI  - Association between intrusive negative autobiographical memories and depression:
      A meta-analytic investigation.
AB  - The study investigated several associations between depression and intrusive
      negative autobiographical memories. A systematic literature search identified 23
      eligible studies (N = 2,582), which provided 59 effect sizes. Separate meta
      analyses indicated that depression was moderately, positively associated with
      intrusive memory frequency, memory distress, maladaptive memory appraisals,
      memory avoidance, and memory rumination. Intrusive memory vividness was not
      significantly associated with depression. There were insufficient data to examine
      the relationship between depression and memory vantage perspective. Between-study
      heterogeneity was high for intrusive memory frequency and memory avoidance, and
      the percentage of females in studies significantly moderated the relationship
      between these variables and depression. An additional exploratory meta-analysis
      (3 studies; N = 257) indicated that intrusive memories were experienced more
      frequently by those with posttraumatic stress disorder than those with
      depression. Overall, the findings suggest that intrusive memories warrant
      clinical attention as they may contribute to the maintenance of depressive
      symptomatology.

PMID- 29473251
TI  - Modelling the influence of parental effects on gene-network evolution.
AB  - Understanding the importance of nongenetic heredity in the evolutionary process
      is a major topic in modern evolutionary biology. We modified a classical gene
      network model by allowing parental transmission of gene expression and studied
      its evolutionary properties through individual-based simulations. We identified
      ontogenetic time (i.e. the time gene networks have to stabilize before being
      submitted to natural selection) as a crucial factor in determining the
      evolutionary impact of this phenotypic inheritance. Indeed, fast-developing
      organisms display enhanced adaptation and greater robustness to mutations when
      evolving in presence of nongenetic inheritance (NGI). In contrast, in our model,
      long development reduces the influence of the inherited state of the gene
      network. NGI thus had a negligible effect on the evolution of gene networks when
      the speed at which transcription levels reach equilibrium is not constrained.
      Nevertheless, simulations show that intergenerational transmission of the gene
      network state negatively affects the evolution of robustness to environmental
      disturbances for either fast- or slow-developing organisms. Therefore, these
      results suggest that the evolutionary consequences of NGI might not be sought
      only in the way species respond to selection, but also on the evolution of
      emergent properties (such as environmental and genetic canalization) in complex
      genetic architectures.

PMID- 29473252
TI  - Transoral radical tonsillectomy and retropharyngeal lymph node dissection with a
      flexible next generation robotic surgical system.
AB  - BACKGROUND: The purpose of this study was to describe the use of a novel
      flexible, single-arm robot in performing a transoral radical tonsillectomy and
      retropharyngeal lymph node dissection. METHODS: A 63-year-old man with a T1N2bM0
      (American Joint Committee on Cancer seventh edition classification) squamous cell
      carcinoma (SCC) of the left tonsil underwent a transoral robotic radical
      tonsillectomy and retropharyngeal lymph node dissection, followed by a left
      selective neck dissection of levels I to IV. RESULTS: The tonsillar tumor was
      removed completely with a negative margin that was followed by a dissection and
      removal of a retropharyngeal lymph node, completed with primary closure of the
      site. A left selective neck dissection was then performed. The patient was
      tolerating an oral diet on postoperative day 1 and had no robotic or surgically
      related complications at 30-day follow-up. CONCLUSION: It is feasible and safe to
      use this novel, flexible, single-arm robot in performing a transoral robotic
      radical tonsillectomy and retropharyngeal lymph node dissection.

PMID- 29473253
TI  - Modern human origins and dispersal: current state of knowledge and future
      directions.

PMID- 29473254
TI  - Can the theory of planned behavior help explain attendance to follow-up care of
      childhood cancer survivors?
AB  - OBJECTIVE: Childhood cancer survivors are at high risk for late effects. Regular
      attendance to long-term follow-up care is recommended and helps monitoring
      survivors' health. Using the theory of planned behavior, we aimed to (1)
      investigate the predictors of the intention to attend follow-up care, and (2)
      examine the associations between perceived control and behavioral intention with
      actual follow-up care attendance in Swiss childhood cancer survivors. METHODS: We
      conducted a questionnaire survey in Swiss childhood cancer survivors (diagnosed
      with cancer aged <16 years between 1990 and 2005; >=5 years since diagnosis). We
      assessed theory of planned behavior-related predictors (attitude, subjective
      norm, perceived control), intention to attend follow-up care, and actual
      attendance. We applied structural equation modeling to investigate predictors of
      intention, and logistic regression models to study the association between
      intention and actual attendance. RESULTS: Of 299 responders (166 [55.5%]
      females), 145 (48.5%) reported attending follow-up care. We found that subjective
      norm, ie, survivors' perceived social pressure and support (coef = 0.90, P <
      0.001), predicted the intention to attend follow-up; attitude and perceived
      control did not. Perceived control (OR = 1.58, 95%CI:1.04-2.41) and intention to
      attend follow-up (OR = 6.43, 95%CI:4.21-9.81) were positively associated with
      attendance. CONCLUSIONS: To increase attendance, an effort should be made to
      sensitize partners, friends, parents, and health care professionals on their
      important role in supporting survivors regarding follow-up care. Additionally,
      interventions promoting personal control over the follow-up attendance might
      further increase regular attendance.

PMID- 29473255
TI  - The Generalized Anxiety Disorder Screener (GAD-7) and the anxiety module of the
      Hospital and Depression Scale (HADS-A) as screening tools for generalized anxiety
      disorder among cancer patients.
AB  - OBJECTIVE: Anxiety in cancer patients may represent a normal psychological
      reaction. To detect patients with pathological levels, appropriate screeners with
      established cut-offs are needed. Given that previous research is sparse, we
      investigated the diagnostic accuracy of 2 frequently used screening tools in
      detecting generalized anxiety disorder (GAD). METHODS: We used data of a
      multicenter study including 2141 cancer patients. Diagnostic accuracy was
      investigated for the Generalized Anxiety Disorder Screener (GAD-7) and the
      anxiety module of the Hospital Anxiety and Depression Scale (HADS-A). GAD,
      assessed with the Composite International Diagnostic Interview for Oncology,
      served as a reference standard. Overall accuracy was measured with the area under
      the receiver operating characteristics curve (AUC). The AUC of the 2 screeners
      were statistically compared. We also calculated accuracy measures for selected
      cut-offs. RESULTS: Diagnostic accuracy could be interpreted as adequate for both
      screeners, with an identical AUC of .81 (95% CI: .79-.82). Consequently, the 2
      screeners did not differ in their performance (P = .86). The best balance between
      sensitivity and specificity was found for cut-offs >=7 (GAD-7) and >=8 (HADS-A).
      The officially recommended thresholds for the GAD-7 (>= 10) and the HADS-A (>=11)
      showed low sensitivities of 55% and 48%, respectively. CONCLUSIONS: The GAD-7 and
      HADS-A showed AUC of adequate diagnostic accuracy and hence are applicable for
      GAD screening in cancer patients. Nevertheless, the choice of optimal cut-offs
      should be carefully evaluated.

PMID- 29473256
TI  - Editorial.

PMID- 29473257
TI  - Mixed adenoneuroendocrine carcinoma of the tongue arising within a congenital
      enteric cyst.
AB  - BACKGROUND: Primary intestinal-type adenocarcinoma of the tongue is rare. This
      represents the first reported case of a primary mixed adenoneuroendocrine
      carcinoma (MANEC) of the tongue arising within a congenital enteric cyst.
      METHODS: A 52-year-old man presented with a midline tongue mass that was
      connected to the mucosal surface with an epithelial-lined sinus tract.
      Morphological examination and immunohistochemical profiling of the neoplasm were
      performed. RESULTS: Histopathological evaluation showed a primary MANEC arising
      within a preexisting congenital enteric cyst, comprising both adenocarcinoma and
      neuroendocrine components. The adenocarcinoma had a colonic-type morphology and
      coexpressed CK7, CK20, and CDX2. Imaging and colonoscopy excluded a distant
      primary colorectal neoplasm. CONCLUSION: The association of primary MANEC of the
      tongue with a gastrointestinal heterotopic cyst supports an origin from entrapped
      endodermal elements as opposed to salivary duct origin. This case raises the
      awareness of a rare yet prognostically important complication of a
      gastrointestinal heterotopic cyst.

PMID- 29473258
TI  - Treating women with opioid use disorder during pregnancy in Appalachia: Initial
      neonatal outcomes following buprenorphine + naloxone exposure.
AB  - BACKGROUND AND OBJECTIVES: Rising concerns regarding diversion and misuse of mono
      buprenorphine for treatment of pregnant women with opioid use disorders have
      sparked interest in the use of buprenorphine + naloxone to reduce misuse and
      diversion rates. Examined the relationship of prenatal buprenorphine + naloxone
      exposure to neonatal outcomes. METHODS: This is a retrospective chart review of
      26 mother infant dyads in comprehensive medication-assisted treatment with
      buprenorphine + naloxone during pregnancy. RESULTS: All neonatal birth outcome
      parameters were within normal ranges, albeit on the lower side of normal for
      gestational age and birth weight. Only 19% of neonates required morphine
      pharmacology for NAS. CONCLUSIONS: Use of buprenorphine + naloxone shows relative
      safety in pregnancy. SCIENTIFIC SIGNIFICANCE: These findings can help better
      guide prescribing practices for pregnant patients at risk for misuse or diversion
      of buprenorphine. (Am J Addict 2018;27:92-96).

PMID- 29473259
TI  - Depression and anxiety symptoms during the transition to early adulthood for
      people with intellectual disabilities.
AB  - BACKGROUND: The transition to adulthood is a major developmental milestone; a
      time of self-discovery and increased independence. For young adults (YA) with
      intellectual disabilities (ID), however, this period is especially challenging.
      The increased incidence of mental health disorders in this population, such as
      depression and anxiety, make this transition even more difficult, increasing
      caregiver burden at a time when the young adult would traditionally be gaining
      independence. It is not clear, however, why YA with ID are more susceptible and
      what factors may predict mental health symptoms. METHOD: Potential risk and
      protective factors (demographic variables, coping styles, sense of hopelessness,
      unmet achievement of adulthood milestones, self-reflection and insight) of
      anxiety and depression symptoms were assessed in 55 YA with ID and a sample of
      age-matched controls. RESULTS: Insight was the strongest predictor of anxiety
      (with gender in the controls) for YA with and without ID, with increased insight
      predicting fewer anxiety symptoms. However, YA with ID had significantly less
      insight than their aged-matched counterparts and significantly higher levels of
      anxiety. They were also less likely to have achieved traditional adulthood
      milestones. Maladaptive coping was the strongest predictor of depression for YA
      with ID. In comparison, both maladaptive coping and insight predicted depression
      in controls. More maladaptive coping predicted increased depressive symptoms in
      both populations, whilst increased insight predicted fewer depressive symptoms in
      controls. CONCLUSIONS: Insight and maladaptive coping are potential targets in
      the treatment of anxiety and depression among YA with ID. Longitudinal
      intervention studies exploring the efficacy of such targeted programmes in
      reducing mental health symptoms and improving the transition to adulthood for
      these young people are recommended.

PMID- 29473260
TI  - Textually mediated discourses in Canadian news stories: Situating nurses'
      salaries as the problem.
AB  - The aim of this article is to elucidate how nurses are positioned in Canadian
      news stories regarding their salaries. While the image of nursing in mass media
      has been widely studied, few studies explore how nurses are constructed in news
      stories. Drawing on ideas from institutional ethnography together with discourse
      analysis, this discussion highlights public textual discourses about nurses'
      salaries in Canadian news stories. The media discourse was found to distort the
      issues by focusing attention on nurses. Recognizing how these textual distortions
      mediate and construct messages is important in understanding how nurses and their
      work are constructed in the media. This discussion seeks to inform readers about
      how nurses are situated within commonly circulated discourses in the media. It
      also seeks to contribute to the literature about the nurse's image and how nurses
      and their work are portrayed in the public realm. It concludes by recommending
      increased awareness about how nurses are talked about in mass communication and
      the need to disrupt these messages and their underlying assumptions.

PMID- 29473261
TI  - Spanish version of the modified Advanced Practice Role Delineation tool,
      adaptation and psychometric properties.
AB  - BACKGROUND: Role clarity is vital to avoid confusion and role ambiguity within
      nursing. There is a need for valid, reliable tools that can delineate the profile
      of advanced nursing practice to measure the extent of advanced practices in
      Spain. AIM: The main purpose of this study was to translate, cross-culturally
      adapt, and psychometrically test the Spanish version of the modified Advanced
      Practice Role Delineation tool. DESIGN: The study was designed to follow
      symmetrical translation and cognitive debriefing to determine conceptual
      equivalence. A cross-sectional survey was conducted to examine content validity
      and psychometric tests. METHODS: Data were collected over 6 months in 2015 and
      2016. The study had a purposive sample of specialist nurses and nurses with an
      extended practice profile beyond that of a general nurse. RESULTS: The study
      achieved conceptual, semantic, and content equivalence of the items. The results
      provided support for the instrument's validity and reliability in advanced
      practice nursing in a tertiary and community hospital. The tool showed internal
      consistency, with a Cronbach's alpha coefficient of 0.86 and stability over time.
      CONCLUSION: The findings should influence future nursing practice, research, and
      leadership while allowing assessment of Spanish advanced practice roles in an
      international context.

PMID- 29473262
TI  - Local functional connectivity suggests functional immaturity in children with
      attention-deficit/hyperactivity disorder.
AB  - Previous studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD)
      with a maturational lag of brain functional networks. Functional connectivity of
      the human brain changes from primarily local to more distant connectivity
      patterns during typical development. Under the maturational lag hypothesis, we
      expect children with ADHD to exhibit increased local connectivity and decreased
      distant connectivity compared with neurotypically developing (ND) children. We
      applied a graph-theory method to compute local and distant connectivity levels
      and cross-sectionally compared them in a sample of 120 children with ADHD and 120
      age-matched ND children (age range = 7-17 years). In addition, we measured if
      potential group differences in local and distant connectivity were stable across
      the age range considered. Finally, we assessed the clinical relevance of observed
      group differences by correlating the connectivity levels and ADHD symptoms
      severity separately for each group. Children with ADHD exhibited more local
      connectivity than age-matched ND children in multiple brain regions, mainly
      overlapping with default mode, fronto-parietal and ventral attentional functional
      networks (p < .05- threshold free-cluster enhancement-family-wise error). We
      detected an atypical developmental pattern of local connectivity in somatomotor
      regions, that is, decreases with age in ND children, and increases with age in
      children with ADHD. Furthermore, local connectivity within somatomotor areas
      correlated positively with clinical severity of ADHD symptoms, both in ADHD and
      ND children. Results suggest an immature functional state of multiple brain
      networks in children with ADHD. Whereas the ADHD diagnosis is associated with the
      integrity of the system comprising the fronto-parietal, default mode and ventral
      attentional networks, the severity of clinical symptoms is related to atypical
      functional connectivity within somatomotor areas. Additionally, our findings are
      in line with the view of ADHD as a disorder of deviated maturational
      trajectories, mainly affecting somatomotor areas, rather than delays that
      normalize with age.

PMID- 29473263
TI  - Spectroscopic and Computational Characterization of Diethylenetriaminepentaacetic
      Acid/Transplutonium Chelates: Evidencing Heterogeneity in the Heavy Actinide(III)
      Series.
AB  - The chemistry of trivalent transplutonium ions (Am3+ , Cm3+ , Bk3+ , Cf3+ , Es3+
      ...) is usually perceived as monotonic and paralleling that of the trivalent
      lanthanide series. Herein, we present the first extended X-ray absorption fine
      structure (EXAFS) study performed on a series of aqueous heavy actinide chelates,
      extending past Cm. The results obtained on diethylenetriaminepentaacetic acid
      (DTPA) complexes of trivalent Am, Cm, Bk, and Cf show a break to much shorter
      metal-oxygen nearest-neighbor bond lengths in the case of Cf3+ . Corroborating
      those results, density functional theory calculations, extended to Es3+ , suggest
      that the shorter Cf-O and Es-O bonds could arise from the departure of the
      coordinated water molecule and contraction of the ligand around the metal
      relative to the other [MIII DTPA(H2 O)]2- (M=Am, Cm, Bk) complexes. Taken
      together, these experimental and theoretical results demonstrate inhomogeneity
      within the trivalent transplutonium series that has been insinuated and debated
      in recent years, and that may also be leveraged for future nuclear waste
      reprocessing technologies.

PMID- 29473264
TI  - Cyanine Photocages Enable Spatial Control of Inducible Cre-Mediated
      Recombination.
AB  - Optical control over protein expression could provide a means to interrogate a
      range of biological processes. One approach has employed caged ligands of the
      estrogen receptor (ER) in combination with broadly used ligand-dependent Cre
      recombinase proteins. Existing approaches use UV or blue wavelengths, which
      hinders their application in tissue settings. Additionally, issues of payload
      diffusion can impede fine spatial control over the recombination process. Here,
      we detail the chemical optimization of a near-infrared (NIR) light-activated
      variant of the ER antagonist cyclofen. These studies resulted in modification of
      both the caging group and payload with lipophilic n-butyl esters. The appendage
      of esters to the cyanine cage improved cellular uptake and retention. The
      installation of a 4-piperidyl ester enabled high spatial resolution of the light
      initiated Cre-mediated recombination event. These studies described chemical
      modifications with potential general utility for improving spatial control of
      intracellular caging strategies. Additionally, these efforts will enable future
      applications to use these molecules in complex physiological settings.

PMID- 29473265
TI  - Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage
      III colorectal cancer.
AB  - We previously reported a phase I clinical trial of a peptide vaccine ring finger
      protein 43 (RNF43) and 34-kDa translocase of the outer mitochondrial membrane
      (TOMM34) combined with uracil-tegafur (UFT)/LV for patients with metastatic
      colorectal cancer (CRC), and demonstrated the safety and immunological
      responsiveness of this combination therapy. In this study, we evaluated
      vaccination-induced immune responses to clarify the survival benefit of the
      combination therapy as adjuvant treatment. We enrolled 44 patients initially in
      an HLA-masked fashion. After the disclosure of HLA, 28 patients were in the HLA
      A*2402-matched and 16 were in the unmatched group. In the HLA-matched group, 14
      patients had positive CTL responses specific for the RNF43 and/or TOMM34 peptides
      after 2 cycles of treatment and 9 had negative responses; in the HLA-unmatched
      group, 10 CTL responses were positive and 2 negative. In the HLA-matched group, 3
      year relapse-free survival (RFS) was significantly better in the positive CTL
      subgroup than in the negative-response subgroup. Patients with negative
      vaccination-induced CTL responses showed a significant trend towards shorter RFS
      than those with positive responses. Moreover, in the HLA-unmatched group, the
      positive CTL response subgroup showed an equally good 3-year RFS as in the HLA
      matched group. In conclusion, vaccination-induced CTL response to peptide
      vaccination could predict survival in the adjuvant setting for stage III CRC.

PMID- 29473267
TI  - Recent Advances in the Synthesis of beta-Functionalized Ketones by Radical
      Mediated 1,2-Rearrangement of Allylic Alcohols.
AB  - beta-Functionalized ketones are a highly important and valuable class of
      compounds that have gained increasing attention from organic chemists due to
      their intensive uses as versatile synthetic intermediates and building blocks in
      complex molecule assembly and natural product synthesis. Accordingly, there is
      continuing interest in the development of new approaches for the synthesis of
      beta-functionalized ketones. In recent years, radical-mediated 1,2-rearrangement
      reactions of allylic alcohols, which proceed through cationic (semipinacol)
      rearrangements or radical (neophyl) rearrangements, have presented an attractive
      and powerful strategy to access various diversely beta-functionalized ketones.
      Interestingly, this strategy allows for the direct installation of a variety of
      valuable functional groups at the beta-position of cyclic and acyclic ketones by
      employing different radical precursors. However, a review focusing on the
      preparation of beta-functionalized ketones by radical-mediated 1,2-rearrangement
      reactions of allylic alcohols has not been summarized to date. This Minireview
      highlights recent progress made in this highly active and interesting research
      area, and the corresponding mechanisms will also be discussed.

PMID- 29473266
TI  - Anti-human SIRPalpha antibody is a new tool for cancer immunotherapy.
AB  - Interaction of signal regulatory protein alpha (SIRPalpha) expressed on the
      surface of macrophages with its ligand CD47 expressed on target cells negatively
      regulates phagocytosis of the latter cells by the former. We recently showed that
      blocking Abs to mouse SIRPalpha enhanced both the Ab-dependent cellular
      phagocytosis (ADCP) activity of mouse macrophages for Burkitt's lymphoma Raji
      cells opsonized with an Ab to CD20 (rituximab) in vitro as well as the inhibitory
      effect of rituximab on the growth of tumors formed by Raji cells in nonobese
      diabetic (NOD)/SCID mice. However, the effects of blocking Abs to human SIRPalpha
      in preclinical cancer models have remained unclear given that such Abs have
      failed to interact with endogenous SIRPalpha expressed on macrophages of
      immunodeficient mice. With the use of Rag2-/- gammac-/- mice harboring a
      transgene for human SIRPalpha under the control of human regulatory elements
      (hSIRPalpha-DKO mice), we here show that a blocking Ab to human SIRPalpha
      significantly enhanced the ADCP activity of macrophages derived from these mice
      for human cancer cells. The anti-human SIRPalpha Ab also markedly enhanced the
      inhibitory effect of rituximab on the growth of tumors formed by Raji cells in
      hSIRPalpha-DKO mice. Our results thus suggest that the combination of Abs to
      human SIRPalpha with therapeutic Abs specific for tumor antigens warrants further
      investigation for potential application to cancer immunotherapy. In addition,
      humanized mice, such as hSIRPalpha-DKO mice, should prove useful for validation
      of the antitumor effects of checkpoint inhibitors before testing in clinical
      trials.

PMID- 29473268
TI  - Metal-Free Dehydrogenation of N-Heterocycles by Ternary h-BCN Nanosheets with
      Visible Light.
AB  - An efficient metal-free catalytic system has been developed based on hexagonal
      boron carbon nitride (h-BCN) nanosheets for the dehydrogenation of N-heterocycles
      with visible light; hydrogen gas is released in the process, and thus no proton
      acceptor is needed. This acceptorless dehydrogenation of hydroquinolines,
      hydroisoquinolines, and indolines to the corresponding aromatic N-heterocycles
      occurred in excellent yield under visible-light irradiation at ambient
      temperature. With h-BCN as the photocatalyst and water as the solvent, this
      environmentally benign protocol shows broad substitution tolerance and high
      efficiency.

PMID- 29473269
TI  - Maternal viral load and hepatitis B virus mother-to-child transmission risk: A
      systematic review and meta-analysis.
AB  - AIM: The aim of this study was to assess the relationship between maternal viral
      load and mother-to-child transmission (MTCT) risk in hepatitis B envelope antigen
      (HBeAg)-positive mothers. METHODS: PubMed and Web of Science were systematically
      searched. We compared MTCT incidence between maternal hepatitis B virus (HBV)-DNA
      positive and HBV-DNA-negative groups. We also examined the dose-response effect
      of this relationship. RESULTS: Twenty-one studies with 10 142 mother-child pairs
      were included in the studies. The mean MTCT incidence was 13.1% in the maternal
      HBV-DNA-positive group, compared with 4.2% in the negative group. The summary
      MTCT odds ratio of maternal HBV-DNA positive compared with negative was 9.895
      (95% confidence interval [CI], 5.333 to 18.359; Z = 7.27, P < 0.00001) by random
      effects model. In maternal HBV-DNA <6 log10 copies/mL, 6-8 log10 copies/mL, and
      >8 log10 copies/mL level stratifications, the pooled MTCT incidences were 2.754%
      (95% CI, 1.198-4.310%; Z = 3.47, P = 0.001), 9.932% (95% CI, 6.349-13.516%; Z =
      5.43, P < 0.00001), and 14.445% (95% CI, 8.317-20.572%; Z = 4.62, P < 0.00001),
      respectively. A significant linear dose-response association was found between
      maternal viral load and MTCT risk, with the points estimate of increased MTCT
      risk 2.705 (95% CI, 1.808-4.047) at 6 log10 copies/mL compared with reference (3
      log10 copies/mL), and 7.316 (95% CI, 3.268-16.378) at 9 log10  copies/mL. A
      significant non-linear dose-response association was also found between maternal
      viral load and HBV MTCT risk (model chi2  = 23.43, P < 0.00001). CONCLUSION: Our
      meta-analysis indicated that maternal viral load was an important risk factor for
      MTCT in HBeAg-positive mothers, and maternal viral load was dose-dependent with
      HBV MTCT incidence.

PMID- 29473270
TI  - Fluoride-Catalyzed Deblocking: A Route to Polymeric Urethanes.
AB  - We report a fluoride-catalyzed deblocking of urethanes as "blocked" isocyanates.
      Organic and inorganic sources of fluoride ion proved effective for deblocking
      urethanes and for converting polyurethanes to small molecules. Distinct from
      conventional deblocking chemistry involving organometallic compounds and high
      temperatures, the method we describe is metal-free and operates at or slightly
      above room temperature. The use of fluorescent blocking agents enabled visual and
      spectroscopic monitoring of blocking/deblocking reactions, and the selected
      conditions proved applicable to urethanes containing a variety of blocking
      groups. The method additionally enabled a one pot deblocking and polymerization
      with alpha,omega-diols. Overall, this deblocking/polymerization strategy offers a
      convenient and efficient solution to problems that have limited the breadth of
      applications of polyurethane chemistry.

PMID- 29473271
TI  - Neutropenia in pediatric heart transplant recipients.
AB  - Neutropenia has been reported in pediatric heart transplant recipients, but its
      association with infectious morbidity and mortality is unknown. We sought to
      determine neutropenia's prevalence and impact on infection, rejection, and
      survival. A retrospective analysis of pediatric heart transplant recipients from
      March 2005 to August 2015 was performed. Demographics, medications, infection,
      and rejection data were collected. Of 142 pediatric heart transplant recipients,
      77 (54.2%) developed neutropenia within 4.7 months [3.3-12.1 months] of
      transplant. In all patients, the adjusted 5-year cumulative incidence of
      neutropenia was 30.2%. Fifty-one patients (66.2%) had recurrent neutropenia. Six
      of 14 tested had positive antineutrophil antibodies. Medications associated with
      neutropenia were decreased in 15 (19.5%) and discontinued in 42 (54.4%) patients
      with no change in 1-year rejection rates compared to published data. Fifteen
      patients developed infection within 30 days of neutropenia and two from 30 days
      to 1 year, with an infection rate similar to the non-neutropenic group. There was
      no significant difference in survival, ANC, rate of rejection or PTLD in
      neutropenic patients with and without infection at median follow-up (5.5 years).
      Neutropenia is common in pediatric heart transplant recipients. Neutropenia had
      <20% risk of associated infection, similar to non-neutropenic patients. Infection
      in neutropenic patients did not increase mortality.

PMID- 29473272
TI  - Li2 B12 and Li3 B12 : Prediction of the Smallest Tubular and Cage-like Boron
      Structures.
AB  - An intriguing structural transition from the quasi-planar form of B12 cluster
      upon the interaction with lithium atoms is reported. High-level computations show
      that the lowest energy structures of LiB12 , Li2 B12 , and Li3 B12 have quasi
      planar (Cs ), tubular (D6d ), and cage-like (Cs ) geometries, respectively. The
      energetic cost of distorting the B12 quasi-planar fragment is overcompensated by
      an enhanced electrostatic interaction between the Li cations and the tubular or
      cage-like B12 fragments, which is the main reason of such drastic structural
      changes, resulting in the smallest tubular (Li2 B12 ) and cage-like (Li3 B12 )
      boron structures reported to date.

PMID- 29473273
TI  - Systematic review of strategies to increase access to health services among
      children over five in low- and middle-income countries.
AB  - BACKGROUND: The populations of many low- and middle-income countries (LMIC) are
      young. Despite progress made towards achieving Universal Health Coverage and
      remarkable health gains, evidence suggests that many children in LMIC are still
      not accessing needed healthcare services. Delayed or lack of access to health
      services can lead to a worsening of health and can in turn negatively impact a
      child's ability to attend school, and future employment opportunities. METHODS:
      We conducted a systematic review to assess the effectiveness of interventions
      aimed at increasing access to health services for children over 5 years in LMIC
      settings. Four electronic databases were searched in March 2017. Studies were
      included if they evaluated interventions that aimed to increase: healthcare
      utilisation, immunisation uptake and compliance with medication/referral.
      Randomised controlled trials and non-randomised study designs were included in
      the review. Data extraction included study characteristics, intervention type and
      measures of access to health services for children above 5 years of age. Study
      outcomes were classified as positive, negative, mixed or null in terms of their
      impact on access outcomes. RESULTS: Ten studies met the criteria for inclusion in
      the review. Interventions were evaluated in Nicaragua (1), Brazil (1), Turkey
      (1), India (1), China (1), Uganda (1), Ghana (1), Nigeria (1), South Africa (1)
      and Swaziland (1). Intervention types included education (2), incentives (1),
      outreach (1), SMS/phone call reminders (2) and multicomponent interventions (4).
      All evaluations reported positive findings on measured health access outcomes;
      however, the quality and strength of evidence were mixed. CONCLUSION: This review
      provides evidence of the range of interventions that were used to increase
      healthcare access for children above 5 years old in LMIC. Nevertheless, further
      research is needed to examine each of the identified intervention types and the
      influence of contextual factors, with robust study designs. There is also a need
      to assess the cost-effectiveness of the interventions to inform decision-makers
      on which are suitable for scale-up in their particular contexts.

PMID- 29473274
TI  - Chaotropic Monovalent Anion-Induced Rectification Inversion at Nanopipettes
      Modified by Polyimidazolium Brushes.
AB  - A nonintuitive observation of monovalent anion-induced ion current rectification
      inversion at polyimidazolium brush (PimB)-modified nanopipettes is presented. The
      rectification inversion degree is strongly dependent on the concentration and
      species of monovalent anions. For chaotropic anions (for example, ClO4- ), the
      rectification inversion is easily observed at a low concentration (5 mm), while
      there is no rectification inversion observed for kosmotropic anions (Cl- ) even
      at a high concentration (1 m). Moreover, at the specific concentration (for
      example, 10 mm), the variation of rectification ratio on the type of anions is
      ranged by Hofmeister series (Cl- >=NO3- >BF4- >ClO4- >PF6- >Tf2 N- ). Estimation
      of the electrokinetic charge density (sigmaek ) demonstrates that rectification
      inversion originates from the charge inversion owing to the over-adsorption of
      chaotropic monovalent anion. To qualitatively understand this phenomenon, a
      concentration-dependent adsorption mechanism is proposed.

PMID- 29473275
TI  - Design, Synthesis, and Application of Chiral C2 -Symmetric Spiroketal-Containing
      Ligands in Transition-Metal Catalysis.
AB  - We present an expedient and economical route to a new spiroketal-based C2 
      symmetric chiral scaffold, termed SPIROL. Based on this spirocyclic scaffold,
      several chiral ligands were generated. These ligands were successfully employed
      in an array of stereoselective transformations, including in iridium-catalyzed
      hydroarylations (up to 95 % ee), palladium-catalyzed allylic alkylations (up to
      97 % ee), intermolecular palladium-catalyzed Heck couplings (up to 94 % ee), and
      rhodium-catalyzed dehydroalanine hydrogenation (up to 93 % ee).

PMID- 29473276
TI  - Validation testing of a short food-group-based questionnaire to assess dietary
      risk in preschoolers aged 3-5 years.

PMID- 29473277
TI  - Formation of p62-positive inclusion body is associated with macrophage
      polarization in non-alcoholic fatty liver disease.
AB  - AIM: Hepatic inclusion composed of autophagy-specific substrate p62 is one of the
      histological features of non-alcoholic fatty liver disease (NAFLD) and can be a
      precursor to hepatic carcinogenesis. The expression of p62 was enhanced by not
      only autophagic dysfunction but also oxidative stress and inflammation. M1/M2
      phenotypic balance of macrophages plays a pivotal role in the progression of
      NAFLD. We evaluated the correlation between macrophage polarization and the
      formation of p62 aggregation in NAFLD. METHODS: Liver biopsy specimens from NAFLD
      patients were analyzed by immunohistochemical staining for M1 macrophage marker
      CD11c, M2 macrophage marker CD163, and p62/SQSTM1 (p62). The histological
      severity of NAFLD is assessed by a NAFLD activity score (NAS). The number of
      autophagic vesicles in hepatocytes was visualized and counted by using
      transmission electron microscopy. RESULTS: The aggregation of p62 was
      undetectable in control, whereas hepatocytes with p62 aggregation were observed
      in approximately 88% of NAFLD specimens. The number of hepatocytes with p62
      aggregation was positively correlated with the number of autophagic vesicles,
      serum alanine aminotransferase, NAS, fibrosis, and the number of CD11c-positive
      cells, but not CD163-positive cells. Assembly of CD11c-positive cells was
      observed around hepatocytes with p62 aggregation. The ratio of CD11c/CD163
      positive macrophages was significantly associated with the formation of p62
      aggregation. CONCLUSIONS: These findings indicate that chronic inflammation by M1
      polarization of macrophages contributes to the disease progression from simple
      steatosis to non-alcoholic steatohepatitis in concert with autophagic
      dysfunction.

PMID- 29473278
TI  - Both widespread PEP-CTERM proteins and exopolysaccharides are required for floc
      formation of Zoogloea resiniphila and other activated sludge bacteria.
AB  - Bacterial floc formation plays a central role in the activated sludge (AS)
      process, which has been widely utilized for sewage and wastewater treatment. The
      formation of AS flocs has long been known to require exopolysaccharide
      biosynthesis. This study demonstrates an additional requirement for a PEP-CTERM
      protein in Zoogloea resiniphila, a dominant AS bacterium harboring a large
      exopolysaccharide biosynthesis gene cluster. Two members of a wide-spread family
      of high copy number-per-genome PEP-CTERM genes, transcriptionally regulated by
      the RpoN sigma factor and accessory PrsK-PrsR two-component system and at least
      one of these, pepA, must be expressed for Zoogloea to build the floc structures
      that allow gravitational sludge settling and recycling. Without PrsK or PrsR,
      Zoogloea cells were planktonic rather than flocculated and secreted
      exopolysaccharides were released into the growth broth in soluble form.
      Overexpression of PepA could circumvent the requirement of rpoN, prsK and prsR
      for the floc-forming phenotype by fixing the exopolysaccharides to bacterial
      cells. However, overexpression of PepA, which underwent post-translational
      modifications, could not rescue the long-rod morphology of the rpoN mutant.
      Consistently, PEP-CTERM genes and exopolysaccharide biosynthesis gene cluster are
      present in the genome of the floc-forming Nitrospira comammox and Mitsuaria
      strain as well as many other AS bacteria.

PMID- 29473279
TI  - Autism spectrum disorder and genetic testing: Parental perceptions and decision
      making.
AB  - PURPOSE: Advances in genomic technology and research have led to genetic testing
      being recognized as an essential component of the etiological workup for children
      with autism spectrum disorder (ASD). Chromosomal microarray analysis (CMA) is a
      first-tier diagnostic test for patients with ASD, as recommended by the American
      College of Medical Genetics and other professional societies. An accurate
      underlying medical diagnosis for ASD has many potential benefits, including
      appropriate medical management, detailed therapeutic recommendations, and
      accurate recurrence risk. Genetic testing is relatively complicated, expensive,
      and, currently, in the majority of the cases, does not provide any organic
      improvement in the management of symptoms. DESIGN AND METHODS: We conducted
      semistructured interviews with 20 parents to explore the decision-making process
      of genetic testing from the perspectives and experiences of parents of children
      with ASD. Data were analyzed using qualitative content analysis. RESULTS: Parents
      had limited knowledge of genetic testing for ASD prior to a genetics clinic
      visit. The majority of the participants thought genetic testing would be
      beneficial for their child, their reproductive choices, and potential future
      generations. PRACTICE IMPLICATIONS: Various stakeholders (geneticists, primary
      care providers, nurses, and families) would benefit from future establishment of
      educational strategies to inform parental decision-making regarding genetic
      testing for children with ASD.

PMID- 29473280
TI  - Effect of platelets-rich plasma on scalp hair diameter.
AB  - OBJECTIVES: To measure the effects of platelet-rich plasma (PRP) on hair diameter
      in Pakistani population. MATERIALS AND METHODS: The study was conducted in a
      private setup in the adult patients undergoing PRP treatment. Baseline platelets
      count was noted for each patient. PRP was prepared using a commercial kit. Three
      PRP injections were administered in the scalp at 0, 1, and 3 months of interval.
      The hair caliber was measured in the mid-scalp area using a separate stencil for
      each patient. The diameter of 10 hair (1 cm sq) was measured randomly using the
      caliper (2 hair on each side of the square and 4 in the center). After 6 months
      of 3rd injection, the hair caliber was measured and the results were analyzed
      statistically using Mann-Whitney's test. RESULTS: Seven men and 3 women were
      included in the study. The mean age of the patients was 24.2 years (26.3 years in
      males and 19.3 in females). The average platelets count was found to be
      283,580/MUL. The mean hair caliber was 37.3 MUm (39.1 MUm in men and 33.0 MUm in
      women). At the end of the study, the mean hair caliber was found to be 52.3 MUm
      (P < .01). The mean hair caliber was 53.9 MUm in men and 48.7 MUm in women (P <
      .01). The increase in the hair caliber was noted to be 27.5% more in men and
      31.3% more in women (P < .01). CONCLUSION: The PRP injections can increase the
      hair diameter.

PMID- 29473281
TI  - Postpartum venous thromboembolism prophylaxis: harm versus benefit.

PMID- 29473282
TI  - Antioxidant action and protective and reparative effects of lentinan on oxidative
      damage in HaCaT cells.
AB  - BACKGROUND: Lentinus edodes is one of the largest edible fungi. Lentinan,
      extracted from its fruiting body has clinically significant anticancer,
      antibacterial, antiviral, and anticoagulant effects; however, its preventive
      effects on skin oxidative damage are unclear. AIMS: We aimed to evaluate the in
      vitro antioxidation capability of lentinan and its protective and reparative
      effects on a model of cell oxidative damage. METHODS: We evaluated the in vitro
      antioxidant potential of lentinan by assessing its free-radical quenching ability
      using DPPH and ABTS and superoxide anions. Using the HaCaT cell line as the
      experimental system, we tested the protective and reparative effects of lentinan
      on a model of H2 O2 -induced cellular oxidative damage through assessment of cell
      survival rate, malondialdehyde (MDA) content, and superoxide dismutase (SOD)
      activity. RESULTS: Lentinan displayed high antioxidant potential: DDPH and ABTS
      quenching rates were above 60%; superoxide anions, approximately 18%.
      Furthermore, lentinan could dose-dependently prevent the reduction of activity in
      HaCaT cells by H2 O2 , reduce MDA formation, and increase SOD activity. Moreover,
      lentinan showed not only a protective effect against oxidative damage but also
      reparative effects to a certain extent, in HaCaT cells. CONCLUSIONS: Our findings
      demonstrated the ability of lentinan to enhance cellular tolerance to oxidative
      damage, stress resistance, and to have protective and reparative effects on
      damaged cells. Therefore, with L. edodes as a source for antiaging substances,
      cosmetics with homology to foods have great potential clinical applications.

PMID- 29473283
TI  - The purple non-sulfur bacterium Rhodopseudomonas palustris produces novel
      petrobactin-related siderophores under aerobic and anaerobic conditions.
AB  - Many bacteria produce siderophores to bind and take up Fe(III), an essential
      trace metal with extremely low solubility in oxygenated environments at
      circumneutral pH. The purple non-sulfur bacterium Rhodopseudomonas palustris str.
      CGA009 is a metabolically versatile model organism with high iron requirements
      that is able to grow under aerobic and anaerobic conditions. Siderophore
      biosynthesis has been predicted by genomic analysis, however, siderophore
      structures were not identified. Here, we elucidate the structure of two novel
      siderophores from R. palustris: rhodopetrobactin A and B. Rhodopetrobactins are
      structural analogues of the known siderophore petrobactin in which the Fe
      chelating moieties are conserved, including two 3,4-dihydroxybenzoate and a
      citrate substructure. In the place of two spermidine linker groups in
      petrobactin, rhodopetrobactins contain two 4,4'-diaminodibutylamine groups of
      which one or both are acetylated at the central amine. We analyse siderophore
      production under different growth modes and show that rhodopetrobactins are
      produced in response to Fe limitation under aerobic as well as under anaerobic
      conditions. Evaluation of the chemical characteristics of rhodopetrobactins
      indicates that they are well suited to support Fe acquisition under variable
      oxygen and light conditions.

PMID- 29473284
TI  - Label-free monitoring of inflammatory tissue conditions using a carrageenan
      induced acute inflammation rat model.
AB  - Although the confirmation of inflammatory changes within tissues at the onset of
      various diseases is critical for the early detection of disease and selection of
      appropriate treatment, most therapies are based on complex and time-consuming
      diagnostic procedures. Raman spectroscopy has the ability to provide non
      invasive, real-time, chemical bonding analysis through the inelastic scattering
      of photons. In this study, we evaluate the feasibility of Raman spectroscopy as a
      new, easy, fast, and accurate diagnostic method to support diagnostic decisions.
      The molecular changes in carrageenan-induced acute inflammation rat tissues were
      assessed by Raman spectroscopy. Volumes of 0 (control), 100, 150, and 200 uL of
      1% carrageenan were administered to rat hind paws to control the degree of
      inflammation. The prominent peaks at [1,062, 1,131] cm-1 and [2,847, 2,881] cm-1
      were selected as characteristic measurements corresponding to the C-C stretching
      vibrational modes and the symmetric and asymmetric C-H (CH2 ) stretching
      vibrational modes, respectively. Principal component analysis of the inflammatory
      Raman spectra enabled graphical representation of the degree of inflammation
      through principal component loading profiles of inflammatory tissues on a two
      dimensional plot. Therefore, Raman spectroscopy with multivariate statistical
      analysis represents a promising method for detecting biomolecular responses based
      on different types of inflammatory tissues.

PMID- 29473285
TI  - Angiogenic factors in pre-eclampsia: implications for clinical practice.

PMID- 29473286
TI  - Colony formation in the cyanobacterium Microcystis.
AB  - Morphological evolution from a unicellular to multicellular state provides
      greater opportunities for organisms to attain larger and more complex living
      forms. As the most common freshwater cyanobacterial genus, Microcystis is a
      unicellular microorganism, with high phenotypic plasticity, which forms colonies
      and blooms in lakes and reservoirs worldwide. We conducted a systematic review of
      field studies from the 1990s to 2017 where Microcystis was dominant. Microcystis
      was detected as the dominant genus in waterbodies from temperate to subtropical
      and tropical zones. Unicellular Microcystis spp. can be induced to form colonies
      by adjusting biotic and abiotic factors in laboratory. Colony formation by cell
      division has been induced by zooplankton filtrate, high Pb2+ concentration, the
      presence of another cyanobacterium (Cylindrospermopsis raciborskii),
      heterotrophic bacteria, and by low temperature and light intensity. Colony
      formation by cell adhesion can be induced by zooplankton grazing, high Ca2+
      concentration, and microcystins. We hypothesise that single cells of all
      Microcystis morphospecies initially form colonies with a similar morphology to
      those found in the early spring. These colonies gradually change their morphology
      to that of M. ichthyoblabe, M. wesenbergii and M. aeruginosa with changing
      environmental conditions. Colony formation provides Microcystis with many
      ecological advantages, including adaption to varying light, sustained growth
      under poor nutrient supply, protection from chemical stressors and protection
      from grazing. These benefits represent passive tactics responding to
      environmental stress. Microcystis colonies form at the cost of decreased specific
      growth rates compared with a unicellular habit. Large colony size allows
      Microcystis to attain rapid floating velocities (maximum recorded for a single
      colony, ~ 10.08 m h-1 ) that enable them to develop and maintain a large biomass
      near the surface of eutrophic lakes, where they may shade and inhibit the growth
      of less-buoyant species in deeper layers. Over time, accompanying species may
      fail to maintain viable populations, allowing Microcystis to dominate.
      Microcystis blooms can be controlled by artificial mixing. Microcystis colonies
      and non-buoyant phytoplankton will be exposed to identical light conditions if
      they are evenly distributed over the water column. In that case, green algae and
      diatoms, which generally have a higher growth rate than Microcystis, will be more
      successful. Under such mixing conditions, other phytoplankton taxa could recover
      and the dominance of Microcystis would be reduced. This review advances our
      understanding of the factors and mechanisms affecting Microcystis colony
      formation and size in the field and laboratory through synthesis of current
      knowledge. The main transition pathways of morphological changes in Microcystis
      provide an example of the phenotypic plasticity of organisms during morphological
      evolution from a unicellular to multicellular state. We emphasise that the
      mechanisms and factors influencing competition among various close morphospecies
      are sometimes paradoxical because these morphospecies are potentially a single
      species. Further work is required to clarify the colony-forming process in
      different Microcystis morphospecies and the seasonal variation in this process.
      This will allow researchers to grow laboratory cultures that more closely reflect
      field morphologies and to optimise artificial mixing to manage blooms more
      effectively.

PMID- 29473287
TI  - A laboratory exercise for detecting microbial contaminants.
AB  - The development and evaluation of a 6-hours laboratory class, based on capillary
      electrophoresis (CE) and the detection of microbial contaminants, is described.
      It can be easily scaled up or down, to suit class sizes up to 188 and completed
      in a shorter time scale. CE uses narrow-bore fused-silica capillaries to separate
      a complex array of large and small molecules. A laboratory exercise has been
      devised to illustrate how CE-based genetic analysis system processes DNA fragment
      analysis to detect three microbial contaminants. The protocol is relatively
      inexpensive and uses standard molecular biology reagents and equipment. (c) 2018
      by The International Union of Biochemistry and Molecular Biology, 46(3):279-284,
      2018.

PMID- 29473288
TI  - Increasing N deposition impacts neither diversity nor functions of deadwood
      inhabiting fungal communities, but adaptation and functional redundancy ensure
      ecosystem function.
AB  - Nitrogen deposition can strongly affect biodiversity, but its specific effects on
      terrestrial microbial communities and their roles for ecosystem functions and
      processes are still unclear. Here, we investigated the impacts of N deposition on
      wood-inhabiting fungi (WIF) and their related ecological functions and processes
      in a highly N-limited deadwood habitat. Based on high-throughput sequencing,
      enzymatic activity assay and measurements of wood decomposition rates, we show
      that N addition has no significant effect on the overall WIF community
      composition or on related ecosystem functions and processes in this habitat.
      Nevertheless, we detected several switches in presence/absence (gain/loss) of
      wood-inhabiting fungal OTUs due to the effect of N addition. The responses of WIF
      differed from previous studies carried out with fungi living in soil and leaf
      litter, which represent less N-limited fungal habitats. Our results suggest that
      adaptation at different levels of organization and functional redundancy may
      explain this buffered response and the resistant microbial-mediated ecosystem
      function and processes against N deposition in highly N-limited habitats.

PMID- 29473289
TI  - Many of the causes of preterm birth and poor fetal growth are genetic and
      intergenerational and unlikely to be affected by short-term interventions.

PMID- 29473291
TI  - Bayesian approach for assessing noninferiority in a three-arm trial with binary
      endpoint.
AB  - With the recent advancement in many therapeutic areas, quest for better and
      enhanced treatment options is ever increasing. While the "efficacy" metric plays
      the most important role in this development, emphasis on other important clinical
      factors such as less intensive side effects, lower toxicity, ease of delivery,
      and other less debilitating factors may result in the selection of treatment
      options, which may not beat current established treatment option in terms
      efficacy, yet prove to be desirable for subgroups of patients. The resultant
      clinical trial by means of which one establishes such slightly less efficacious
      treatment is known as noninferiority (NI) trial. Noninferiority trials often
      involve an active established comparator arm, along with a placebo and an
      experimental treatment arm, resulting into a 3-arm trial. Most of the past
      developments in a 3-arm NI trial consider defining a prespecified fraction of
      unknown effect size of reference drug, i.e., without directly specifying a fixed
      NI margin. However, in some recent developments, more direct approach is being
      considered with prespecified fixed margin, albeit in the frequentist setup. In
      this article, we consider Bayesian implementation of such trial when primary
      outcome of interest is binary. Bayesian paradigm is important, as it provides a
      path to integrate historical trials and current trial information via sequential
      learning. We use several approximation-based and 2 exact fully Bayesian methods
      to evaluate the feasibility of the proposed approach. Finally, a clinical trial
      example is reanalyzed to demonstrate the benefit of the proposed approach.

PMID- 29473290
TI  - Estimating gestational age at birth from fundal height and additional
      anthropometrics: a prospective cohort study.
AB  - OBJECTIVE: Accurate assessment of gestational age (GA) is critical to paediatric
      care, but is limited in developing countries without access to ultrasound. Our
      objectives were to assess the accuracy of prediction of GA at birth and preterm
      birth classification using routinely collected anthropometry measures. DESIGN:
      Prospective cohort study. SETTING: United States. POPULATION OR SAMPLE: A total
      of 2334 non-obese and 468 obese pregnant women. METHODS: Enrolment GA was
      determined based on last menstrual period, confirmed by first-trimester
      ultrasound. Maternal anthropometry and fundal height (FH) were measured by a
      standardised protocol at study visits; FH alone was additionally abstracted from
      medical charts. Neonatal anthropometry measurements were obtained at birth. To
      estimate GA at delivery, we developed three predictor models using longitudinal
      FH alone and with maternal and neonatal anthropometry. For all predictors, we
      repeatedly sampled observations to construct training (60%) and test (40%) sets.
      Linear mixed models incorporated longitudinal maternal anthropometry and a shared
      parameter model incorporated neonatal anthropometry. We assessed models' accuracy
      under varied scenarios. MAIN OUTCOME MEASURES: Estimated GA at delivery. RESULTS:
      Prediction error for various combinations of anthropometric measures ranged
      between 13.9 and 14.9 days. Longitudinal FH alone predicted GA within 14.9 days
      with relatively stable prediction errors across individual race/ethnicities
      [whites (13.9 days), blacks (15.1 days), Hispanics (15.5 days) and Asians (13.1
      days)], and correctly identified 75% of preterm births. The model was robust to
      additional scenarios. CONCLUSIONS: In low-risk, non-obese women, longitudinal FH
      measures alone can provide a reasonably accurate assessment of GA when ultrasound
      measures are not available. TWEETABLE ABSTRACT: Longitudinal fundal height alone
      predicts gestational age at birth when ultrasound measures are unavailable.

PMID- 29473292
TI  - Polyphenolic Compounds Alter Stress-Induced Patterns of Global DNA Methylation in
      Brain and Blood.
AB  - SCOPE: Stress is a known contributor to various forms of disease in humans and
      animals, although mechanisms are still unknown. In animals, psychosocial stress
      induced depression/anxiety phenotypes are coincidental with increased
      inflammation in both brain and blood. The authors recently showed that a novel
      treatment with a select bioactive polyphenol preparation promotes resilience to
      stress-mediated depression/anxiety phenotypes mice. Moreover, selective bioactive
      phenolic compounds within the polyphenol preparation are identified that are
      effective in mitigating the behavioral effects of bone marrow transplantation
      from stressed mice. METHODS AND RESULTS: Here, an animal model of adult stress
      and bone marrow transplantation is used to identify an epigenetic signature of
      repeated social defeat stress (RSDS) that is passed through bone marrow
      hematopoietic progenitor cells to naive mice, revealing the maintenance of
      epigenetic memory following stress both centrally and peripherally. Further,
      polyphenols are administered to naive and stress-susceptible mice, demonstrating
      that polyphenol treatment in mice from both susceptible and naive donors alters
      global DNA methylation in the central nervous system and periphery and likewise
      has an effect on human blood cells after immune challenge. CONCLUSIONS: Findings
      highlight the enduring molecular memory of stress and the possible mechanism by
      which select bioactive polyphenols may promote resiliency to stress. Polyphenols
      may be an efficacious alternative to traditional pharmacological treatments in
      psychiatry.

PMID- 29473293
TI  - Highly Sensitive and Stretchable Resistive Strain Sensors Based on
      Microstructured Metal Nanowire/Elastomer Composite Films.
AB  - High sensitivity and high stretchability are two conflicting characteristics that
      are difficult to achieve simultaneously in elastic strain sensors. A highly
      sensitive and stretchable strain sensor comprising a microstructured metal
      nanowire (mNW)/elastomer composite film is presented. The surface structure is
      easily prepared by combining an mNW coating and soft-lithographic replication
      processes in a simple and reproducible manner. The densely packed microprism
      array architecture of the composite film leads to a large morphological change in
      the mNW percolation network by efficiently concentrating the strain in the valley
      regions upon stretching. Meanwhile, the percolation network comprising mNWs with
      a high aspect ratio is stable enough to prevent electrical failure, even under
      high strains. This enables the sensor to simultaneously satisfy high sensitivity
      (gauge factor ~81 at >130% strain) and high stretchability (150%) while ensuring
      long-term reliability (10 000 cycles at 150% strain). The sensor can also detect
      strain induced by bending and pressure, thus demonstrating its potential as a
      versatile sensing tool. The sensor is successfully utilized to monitor a wide
      range of human motions in real time. Furthermore, the unique sensing mechanism is
      easily extended to detect more complex multiaxial strains by optimizing the
      surface morphology of the device.

PMID- 29473294
TI  - Fast Postmoisture Treatment of Luminescent Perovskite Films for Efficient Light
      Emitting Diodes.
AB  - Despite the recent advances in the performance of perovskite light-emitting
      diodes (PeLEDs), the effects of water on the perovskite emissive layer and its
      electroluminescence are still unclear, even though it has been previously
      demonstrated that moisture has a significant impact on the quality of perovskite
      films in the fabrication process of perovskite solar cells and is a prerequisite
      for obtaining high-performance PeLEDs. Here, the effects of postmoisture on the
      luminescent CH3 NH3 PbBr3 (MAPbBr3 ) perovskite films are systematically
      investigated. It is found that postmoisture treatment can efficiently control the
      morphology and growth of perovskite films and only a fast moisture exposure at a
      60% high relative humidity results in significantly improved crystallinity,
      carrier lifetime, and photoluminescence quantum yield of perovskite films. With
      the optimized moisture-treated perovskite films, a high-performance PeLED is
      fabricated, exhibiting a maximum current efficiency of 20.4 cd A-1 , which is an
      almost 20-fold enhancement when compared with perovskite films without moisture
      treatment. The results provide valuable insights into the moisture-assisted
      growth of luminescent perovskite films and will aid in the development of high
      performance perovskite light-emitting devices.

PMID- 29473295
TI  - Bayesian joint modelling of benefit and risk in drug development.
AB  - To gain regulatory approval, a new medicine must demonstrate that its benefits
      outweigh any potential risks, ie, that the benefit-risk balance is favourable
      towards the new medicine. For transparency and clarity of the decision, a
      structured and consistent approach to benefit-risk assessment that quantifies
      uncertainties and accounts for underlying dependencies is desirable. This paper
      proposes two approaches to benefit-risk evaluation, both based on the idea of
      joint modelling of mixed outcomes that are potentially dependent at the subject
      level. Using Bayesian inference, the two approaches offer interpretability and
      efficiency to enhance qualitative frameworks. Simulation studies show that
      accounting for correlation leads to a more accurate assessment of the strength of
      evidence to support benefit-risk profiles of interest. Several graphical
      approaches are proposed that can be used to communicate the benefit-risk balance
      to project teams. Finally, the two approaches are illustrated in a case study
      using real clinical trial data.

PMID- 29473296
TI  - Community-based lymphedema risk reduction programs for cancer survivors: An
      Internet survey of public health nurses.
AB  - AIM: Currently, there is no provision for continuous care to monitor lymphedema
      risk-reduction behavior for survivors of cancer. The aim was to explore the
      possibility of community-based lymphedema education programs by investigating the
      knowledge, training needs, and intention to organize such programs and barriers
      among government-employed public health nurses. METHODS: A cross-sectional
      Internet survey was conducted among government-employed public health nurses in
      Japan. The participants were recruited from 2841 health center and community
      health centers. RESULTS: The final sample included 641 government-employed public
      health nurses. The participants' knowledge about lymphedema risk-reduction
      strategies was relatively good, especially on the importance of observation,
      detection of early signs, and referral to lymphedema clinics. A small proportion
      of participants indicated an intention to organize community-based lymphedema
      education programs. Three determinants for this intention were identified: a
      general interest in lymphedema education, past experience of undertaking training
      in lymphedema risk-reduction strategies, and the perceived difficulty in
      organizing community-based lymphedema education programs. The participants'
      perceptions of difficulty included not knowing the needs for lymphedema education
      in their community with survivors of cancer. CONCLUSIONS: The results suggest
      that working collaboratively with government-employed public health nurses to
      organize community-based lymphedema education programs is possible. Achieving
      this requires further investigation of the needs of survivors of cancer in the
      community, communicating these needs to governmental agencies, and organizing and
      delivering comprehensive training programs about lymphedema risk-reduction
      strategies for government-employed public health nurses.

PMID- 29473297
TI  - Promoting collaboration in emergency medicine.
AB  - BACKGROUND: Collaborative practice between paramedics and medical staff is
      essential for ensuring the safe handover of patients. Handover of care is a
      critical time in the patient journey, when effective communication and
      collaborative practice are central to promoting patient safety and to avoiding
      medical error. To encourage effective collaboration between paramedic and medical
      students, an innovative, practice-based simulation exercise, known as
      interprofessional clinical skills (ICS) was developed at the University of East
      Anglia, UK. Emphasising patient safety, effective handover of care and teamwork,
      within the context of emergency medicine, the ICS promotes collaborative practice
      amongst health care students through the use of high- and low-fidelity
      simulation, human factors and values-based practice. METHODS: A total of 123
      undergraduate students from paramedic (60) and medical backgrounds (63) took part
      in the ICS. Evaluation data were collected from all students through the
      completion of an internal feedback/satisfaction questionnaire with 13 statements
      and one open-ended comment box. RESULTS: The response rate for the questionnaire
      was 100%. Of the 123 students from paramedic and medical disciplines, 99% agreed
      or strongly agreed with the statement 'I enjoyed this session'. Students also
      felt that the ICS helped them to build mutual respect (98%), enhance
      understanding of roles (94%) and develop as collaborative practitioners (92%).
      Collaborative practice between paramedics and medical staff is essential
      CONCLUSION: The ICS is an innovative, enjoyable and meaningful intervention for
      promoting interprofessional collaborative practice between paramedic and medical
      students in a simulated practice setting. It encourages students to gain core
      training in clinical skills and patient safety, within a safe, supervised
      environment.

PMID- 29473298
TI  - Thermoelectric Effects of Nanogaps between Two Tips.
AB  - This study designs a microscaled thermoelectric component featuring a nanogap of
      varying size (133-900 nm) between the tips of the component. Electricity and heat
      are transmitted between the gap of the tips through the thermionic emission of
      electrons. Because the gaps exhibit a discontinuous structure, the phonon's
      contribution to thermal conductivity can be virtually neglected, thereby
      enhancing the thermoelectric figure of merit (ZT) of the designed thermoelectric
      component. The experimental results reveal that a narrow tip gap generates
      stronger thermoelectric effects, with Seebeck voltage and Seebeck coefficient
      being respectively, one and two orders of magnitude greater than those of the
      thermoelectric effects of nanowires. The thermoelectric figure of merit without
      considering the contributions from other heat carriers is higher than the value
      of thermoelectric devices developed in recent years. For a set of asymmetrical
      thin film electrodes of differing sizes, the thermoelectric effects generated in
      the heating process of large thin films are stronger than those of small thin
      films. Furthermore, adding nanoparticles to the nanogap facilitate the thermionic
      emission of electrons, in which electrons hop from the hot end to the cold end,
      thereby intensifying the thermoelectric effects of the nanogap.

PMID- 29473299
TI  - Short-Wave Infrared Sensor by the Photothermal Effect of Colloidal Gold Nanorods.
AB  - Photodetection in the short-wave infrared (SWIR) spectrum is a challenging task
      achieved often by costly low bandgap compound semiconductors involving highly
      toxic elements. In this work, an alternative low-cost approach is reported for
      SWIR sensors that rely on the plasmonic-induced photothermal effect of solution
      processed colloidal gold nanorods (Au NRs). A series of uniform solution
      processed Au NRs of various aspect ratios are prepared exhibiting a strong and
      well-defined longitudinal localized surface plasmon resonance (L-LSPR) maximum
      from 900 nm to 1.3 um. A hybrid device structure is fabricated by applying Au NRs
      on the surface of a thermistor. Under a monochromatic illumination, hybrid Au
      NR/thermistor devices exhibit a clear photoresponse in the form of photoinduced
      resistance drop in the wavelength window from 1.0 to 1.8 um. The
      photoresponsivity of such hybrid devices reaches a maximum value of 4.44 * 107
      Omega W-1 at lambda = 1.4 um (intensity = 0.28 mW cm-2 ), a wavelength in
      agreement with the L-LSPR of the Au NRs applied. Colloidal Au NRs, capable to
      perform fast conversion between photon absorption and thermal energy, thus open
      an interesting avenue for alternative low-cost SWIR photodetection.

PMID- 29473300
TI  - Review article: Managing medical emergencies in rural Australia: A systematic
      review of the training needs.
AB  - The aim of the study was to determine the training needs of doctors managing
      emergencies in rural and remote Australia. A systematic review of Australian
      articles was performed using MEDLINE (OVID) and INFORMIT online databases from
      1990 to 2016. The search terms included 'Rural Health', 'Emergency Medicine',
      'Emergency Medical Services', 'Education, Medical, Continuing' and 'Family
      Practice'. Only peer-reviewed articles, available in full-text that focussed on
      the training needs of rural doctors were reviewed. Data was extracted using pre
      defined fields such as date of data collection, number of participants,
      characteristics of participants, location and study findings. A total of eight
      studies published from 1998 to 2006 were found to be suitable for inclusion in
      the analysis. Six studies cited the results of self-reported questionnaires and
      surveys, one used a telephone questionnaire on a hypothetical patient and one
      utilised a theoretical examination. The studies found a significant proportion of
      participants wanted more emergency training. Junior rural doctors were found to
      have deficiencies in knowledge about stroke. Emergency skills doctors wanted more
      training including: emergency ultrasound, paediatric/neonatal procedures and
      cricothyroidotomy. However, many of the studies were performed by training
      providers that may benefit from deficient results. Given that the data was over
      10 years old and that advances have been made in knowledge, training
      opportunities and technology, the implications for current training needs of
      rural doctors in Australia could not be accurately assessed. Thus there is a need
      for further research to identify current training needs.

PMID- 29473301
TI  - A novel ultra high-performance liquid chromatography-tandem mass spectrometry
      method for the simultaneous determination of xanthones and steroidal saponins in
      crude and salt-processed Anemarrhenae Rhizoma aqueous extracts.
AB  - We established a rapid and sensitive ultra high-performance liquid chromatography
      tandem mass spectrometry method for the simultaneous quantification of xanthones
      and steroidal saponins in rat plasma. Chromatographic separation was achieved on
      a C18 column with a mobile phase comprising acetonitrile and 0.1% formic acid.
      The detection was performed by negative electrospray ionization in multiple
      reaction monitoring mode. The validated method showed good linearity within the
      tested range (r > 0.9945). The intra- and interday precision at high, medium, and
      low concentrations was less than 7.96%. The bias of accuracies ranged from -1.92
      to 9.62%. The extraction recoveries of the compounds ranged from 84.78 to 88.69%,
      and the matrix effects ranged from 96.76 to 108.59%. This method was successfully
      applied to a pharmacokinetic comparison of crude and salt-processed Anemarrhenae
      Rhizoma aqueous extracts after oral administration in rats. The maximum plasma
      concentration and area under concentration-time curve of timosaponin BIII and
      timosaponin AIII increased significantly (P < 0.05 or 0.01) and those of
      timosaponin BII decreased significantly (P < 0.05) after processing. These
      results could contribute to the clinical application of crude and salt-processed
      Anemarrhenae Rhizoma and reveal the processing mechanism.

PMID- 29473302
TI  - Afebrile Kawasaki disease is not a benign form of the disease: Reply.

PMID- 29473303
TI  - Ethylene glycol intoxication presenting with high anion gap metabolic acidosis,
      acute kidney injury and elevated lactate.

PMID- 29473305
TI  - Erratum.

PMID- 29473304
TI  - Non-enhanced magnetic resonance imaging versus renal scintigraphy in acute
      pyelonephritis.
AB  - The utility of non-enhanced magnetic resonance imaging (MRI) has not been
      examined extensively for diagnosing acute pyelonephritis (APN) in children. The
      aims of this study were to compare non-enhanced MRI with technetium-99 m
      dimercaptosuccinic acid (99m Tc-DMSA) renal scintigraphy in detecting APN. Six
      boys and one girl with temperature >=38 degrees C and positive urine culture
      received both non-enhanced MRI with whole body diffusion-weighted imaging (DWI)
      and 99m Tc-DMSA scintigraphy <=7 days from the fever onset. The sensitivity and
      specificity of MRI in detecting APN lesions diagnosed on 99m Tc-DMSA scintigraphy
      were 80% and 100%, respectively. Non-enhanced MRI in children with suspected APN
      <=7 days from fever onset might be a suitable replacement for 99m Tc-DMSA
      scintigraphy for the detection of APN.

PMID- 29473306
TI  - Adequate working hours and skill earning.

PMID- 29473307
TI  - Lupus erythematosus tumidus: Benign disease in children?

PMID- 29473308
TI  - A Room-Temperature Postsynthetic Ligand Exchange Strategy to Construct Mesoporous
      Fe-Doped CoP Hollow Triangle Plate Arrays for Efficient Electrocatalytic Water
      Splitting.
AB  - Hollow nanostructures with mesoporous shells are attractive for their
      advantageous structure-dependent high-efficiency electrochemical catalytic
      performances. In this work, a novel nanostructure of Fe-doped CoP hollow triangle
      plate arrays (Fe-CoP HTPAs) with unique mesoporous shells is designed and
      synthesized through a room-temperature postsynthetic ligand exchange reaction
      followed by a facile phosphorization treatment. The mild postsynthetic ligand
      exchange reaction of the presynthesized ZIF-67 TPAs with K4 [Fe(CN)6 ] in an
      aqueous solution at room temperature is of critical importance in achieving the
      final hollow nanostructure, which results in the production of CoFe(II)-PBA HTPAs
      that not only determine the formation of the interior voids in the nanostructure,
      but also provide the doping of Fe atoms to the CoP lattice. As expected, the as
      prepared mesoporous Fe-CoP HTPAs exhibit pronounced activity for water splitting
      owing to the advantages of abundant active reaction sites, short electron and ion
      pathways, and favorable hydrogen adsorption free energy (DeltaGH* ). For the
      hydrogen and oxygen evolution reactions with the Fe-CoP HTPAs in alkaline medium,
      the low overpotentials of 98 and 230 mV are observed, respectively, and the
      required cell voltage toward overall water splitting is only as low as 1.59 V for
      the driving current density of 10 mA cm-2 .

PMID- 29473309
TI  - Efficacy of mirabegron for overactive bladder with human T cell lymphotropic
      virus-1 associated myelopathy.
AB  - OBJECTIVE: Mirabegron is widely considered as an effective and safe drug for
      patients with overactive bladder (OAB). However, there is no evidence regarding
      the efficacy of mirabegron in human T cell lymphotropic virus-1 (HTLV-1)
      associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with OAB
      symptoms. The aim of the present study was to clarify the efficacy of mirabegron
      in HAM/TSP patients with OAB symptoms. METHODS: The present study evaluated the
      efficacy of mirabegron treatment (50 mg, once daily) in nineteen HAM/TSP patients
      with OAB symptoms by assessing subjective symptoms using the overactive bladder
      symptom score (OABSS) and International Prostate Symptom Score (IPSS) before and
      12 weeks after administration. Voided volume (VV), maximum flow rate (Qmax ), and
      post-void residual (PVR) urine volume were evaluated as objective symptoms.
      RESULTS: Mirabegron treatment improved OABSS in terms of night-time frequency,
      urgency, and total score (P < .001). In addition, on the IPSS, mirabegron therapy
      improved urgency, nocturia, storage symptoms (Questions 2, 4 and 7 on the IPSS),
      as well as the total score (P < .001). The quality of life (QoL) on the IPSS also
      improved after treatment (P < .001). However, there were no significant changes
      in objective symptoms, as measured by VV, Qmax , and PVR, after treatment. One
      patient (5.3%) complained of dry mouth; because this adverse effect was very
      mild, the patient did not discontinue mirabegron. CONCLUSIONS: Mirabegron
      administration improved subjective symptoms in HAM/TSP patients with neurogenic
      OAB.

PMID- 29473310
TI  - Microbiome Yarns: human milk oligosaccharides, Bifidobacterium and
      immunopowergames1,2,3,4.

PMID- 29473312
TI  - Method for the simultaneous determination of monoaromatic and polycyclic aromatic
      hydrocarbons in industrial effluents using dispersive liquid-liquid
      microextraction with gas chromatography-mass spectrometry.
AB  - We present a new method for simultaneous determination of 22 monoaromatic and
      polycyclic aromatic hydrocarbons in postoxidative effluents from the production
      of petroleum bitumen using dispersive liquid-liquid microextraction coupled to
      gas chromatography and mass spectrometry. The eight extraction parameters
      including the type and volume of extraction and disperser solvent, pH, salting
      out effect, extraction, and centrifugation time were optimized. The low detection
      limit ranging from 0.36 to 28 MUg/L, limit of quantitation (1.1-84 MUg/L), good
      reproducibility, and wide linear ranges, as well as the recoveries ranging from
      71.74 to 114.67% revealed that the new method allows the determination of
      aromatic hydrocarbons at low concentration levels in industrial effluents having
      a very complex composition. The developed method was applied to the determination
      of content of mono- and polycyclic aromatic hydrocarbons in samples of raw
      postoxidative effluents in which 15 compounds were identified at concentrations
      ranging from 1.21 to 1017.0 MUg/L as well as in effluents after chemical
      treatment.

PMID- 29473311
TI  - HER3 expression is enhanced during progression of lung adenocarcinoma without
      EGFR mutation from stage 0 to IA1.
AB  - BACKGROUND: Activating EGFR mutations, HER2, and HER3 are implicated in lung
      cancer; however, with the exception of EGFR gene amplification in lung
      adenocarcinoma harboring EGFR mutations, their involvement in disease progression
      during the early stages is poorly understood. In this paper, we focused on which
      receptor is correlated with lung adenocarcinoma progression in the presence or
      absence of EGFR mutation from stage 0 to IA1. METHODS: HER2 and HER3 expression
      and activating EGFR mutations in surgically resected lung adenocarcinoma
      exhibiting ground glass nodules on chest computed tomography and re-classified to
      stage 0 and IA1 were examined by immunohistochemistry and peptide nucleic acid
      locked nucleic acid PCR clamp method, respectively. RESULTS: HER2 and HER3
      expression was detected in 22.2% and 86.1% of samples, respectively. The
      frequency of EGFR mutation was 45.7% and was not significantly different between
      stage 0 and IA1 (40.0% and 48.0%, respectively), suggesting that EGFR mutation
      does not correlate with cancer progression from stage 0 to IA1. HER2 expression
      also did not correlate to progression. However, not only the frequency, but also
      the intensity of HER3 expression was increased in stage IA1 lung adenocarcinoma,
      particularly in lung adenocarcinoma without EGFR mutation. CONCLUSION: HER3 tends
      to be intensively expressed during the progression of lung adenocarcinoma without
      EGFR mutation from carcinoma in situ to invasive carcinoma.

PMID- 29473313
TI  - Vectorial localization of peripheral pulmonary lesion guided by electromagnetic
      navigation: A novel method for diagnostic surgical resection without dye marking.
AB  - We describe a novel method using electromagnetic navigation bronchoscopy (ENB)
      without dye marking to perform vectorial localization for an impalpable
      peripheral lesion in the right lower lobe during diagnostic surgical resection in
      a 52-year-old woman. After the ENB registration process, the anesthetist changed
      the single-lumen endotracheal tube to a double-lumen endobronchial tube. Guided
      by the ENB system, the operator delivered the probe of the locatable guide to the
      planned site through the right lumen of the endobronchial tube. The ENB system
      allows calculation of the direction and distance between the probe and the
      lesion, confirming the relative location of the lesion. The locatable guide was
      retained during surgery as an intraoperative indicator, rather than applying dye
      marking. During video-assisted thoracoscopic surgery, the protuberant visceral
      pleura poked by the probe accurately indicated the relative location of the
      lesion. Accordingly, we performed precise wedge resection for diagnosis, followed
      by lobectomy, resulting in a diagnosis of invasive adenocarcinoma. Vectorial
      localization is an alternative method of ENB-guided localization to peripheral
      pulmonary lesions, which can provide the accurate location of such lesions for
      diagnostic surgical resection.

PMID- 29473314
TI  - The effect of protracted X-ray exposure on cell survival and metabolic activity
      of fast and slow growing fungi capable of melanogenesis.
AB  - The aim of this study was to analyse how protracted exposure to X-rays delivered
      at low dose rates of 0.0032-0.052 kGy h-1 affects the survival and metabolic
      activity of two microfungi capable of melanogenesis: fast-growing Cryptococcus
      neoformans (CN) and slow-growing Cryomyces antarcticus (CA). Melanized CN and CA
      cells survived the protracted exposure better than non-melanized ones, which was
      consistent with previous reports on the radioprotective role of melanin in these
      fungi after high dose rate exposures. The survival data were described by the
      linear quadratic dose response model. The XTT metabolic profiles were practically
      identical for melanized CN and CA with activity dose-dependent increasing: no
      changes in the activity of the non-melanized CN and CA were recorded by this
      assay. In contrast, the MTT assay, which measures the intracellular energy
      related processes, recorded an increase in activity of non-melanized CN and CA
      cells, but not in their melanized counterparts. This could reflect intensive
      repair processes initiated by the non-melanized cells post exposure. This study
      suggests that differences in radiation responses between melanized and non
      melanized fungal cells occur over a wide range of radiation dose rates.

PMID- 29473315
TI  - Photophysics and Photocatalysis of Melem: A Spectroscopic Reinvestigation.
AB  - Graphitic carbon nitride (g-CN) is one potential metal-free photocatalyst. The
      photocatalytic mechanism of g-CN is related to the heptazine ring building unit.
      Melem is the simplest heptazine-based compound and g-CN is its polymeric product.
      Thus, studies on the photophysical properties of melem will help to understand
      the photocatalytic mechanism of heptazine-based materials. Herein, the
      spectroscopic features of melem were systematically explored through measuring
      its absorption spectrum, fluorescence spectrum, and fluorescence decay. Both
      fluorescence spectroscopy and fluorescence decay measurements show that the
      condensation of melamine to melem causes stronger photoluminescence, whereas the
      condensation of melem to g-CN causes weaker photoluminescence. In addition, all
      observations reveal that a mixture of monomer melem and its higher condensates is
      more easily obtained during the preparation of melem, and that the higher
      condensates of melem affect the photophysical properties of melem dominantly. The
      photocatalytic hydrogen evolution of melem has also been measured and the monomer
      melem has negligible photoinduced water-splitting activity.

PMID- 29473316
TI  - Late dislocation of a hydrophilic intraocular lens: risk ratios for predisposing
      factors and incidence rates.

PMID- 29473317
TI  - MiR-634 sensitizes glioma cells to temozolomide by targeting CYR61 through Raf
      ERK signaling pathway.
AB  - Glioma is the most common intracranial malignant tumors, accounting for about 40%
      of intracranial tumors. Primary or secondary drug resistance is one of the main
      reasons for the failure of treatment. The oncogenic or tumor-suppressive roles of
      miR-634 have been revealed in different types of cancer. However, the role of miR
      634 in glioma remains unknown and whether miR-634 could sensitize glioma cells to
      temozolomide also is unclear. Here, we aim to investigate the biological function
      of miR-634 and the possible mechanisms in glioma. In this study, we found that
      miR-634 was downregulated in glioma tissues compared with normal brain tissues,
      and its expression was associated with tumor size and WHO grade. Importantly,
      glioma patients with low miR-634 expression showed a shorter survival time than
      patients which had high expression of miR-634. This study also showed that miR
      634 was decreased in temozolomide-resistant glioma cells, and restoration of miR
      634 could sensitize the resistant cells to temozolomide by targeting CYR61
      through Raf-ERK signaling. Our study provides a potential target for overcome
      drug resistance in glioma.

PMID- 29473319
TI  - Prognostic variables for temporal lobe injury after intensity modulated
      radiotherapy of nasopharyngeal carcinoma.
AB  - To determine predictive factors for temporal lobe injury (TLI) in nasopharyngeal
      carcinoma patient (NPC) treated with intensity-modulated radiation therapy
      (IMRT). A total of 695 NPC cases treated with IMRT were retrospectively analyzed.
      TLI was diagnosed on MRI images. Volume-dose histograms for 870 evaluable
      temporal lobes were analyzed, and the predictive factors for the occurrence of
      TLI was evaluated. Receiver operating characteristic curve (ROC) and Logistic
      regression analysis was used to determine volume-dose parameters that predict
      temporal lobe injury (TLI). Univariate and multivariate analysis were used to
      analyze the predictive factors for TLI. The radiation dose-tolerance model of
      temporal lobe was calculated by logistic dose-response model. The median follow
      up time was 73 months. A total of 8.5% patients were diagnosed with TLI. Among
      all the volume-dose parameters, logistic regression model showed D2cc (the dose
      Gray delivered to 2 cubic centimeter volume) was an only independent predictive
      factor. Multivariate analysis showed D2cc of temporal lobe, fraction size of
      prescription, T stage, and chemotherapy were the independent predictive factors
      for TLI. Logistic dose-response model has indicated the TD5/5 and TD50/5 of D2cc
      are 60.3 Gy and 76.9 Gy, respectively. D2cc of temporal lobe, fraction size of
      prescription, T stage, and chemotherapy were the possible independent predictive
      factors for TLI after IMRT of NPC. Biologic effective doses (TD5/5 and TD50/5 )
      of D2cc are considered to prevent TLI.

PMID- 29473318
TI  - First report on characterization and pathogenicity study of emerging Lactococcus
      garvieae infection in farmed rainbow trout, Oncorhynchus mykiss (Walbaum), from
      India.
AB  - "Warm water lactococcosis" in farm-reared rainbow trout, Oncorhynchus mykiss
      (Walbaum) in the northern Himalayan region of India, caused by bacterium
      Lactococcus garvieae is described in this study. Nine bacterial isolates were
      recovered from the organs of haemorrhagic septicaemia rainbow trout and were
      subjected to biochemical and molecular identification. Cell surface
      characteristics and virulence of the bacterial isolates are also described. All
      the nine bacterial isolates had homogenous biochemical characteristics and were
      Gram-positive, short chains forming (two to eight cells long), alpha-haemolytic,
      non-motile ovoid cocci. Partial 16S rDNA nucleotide sequence (~1,400 bp) of
      current isolates shared 99% identities with the 16S rDNA nucleotide sequence of
      L. garvieae R421, L. garvieae FMA395 and L. garvieae CAU:1730. The identity of
      the bacterial isolates was further confirmed by PCR amplification of L. garvieae
      specific ~1,100 bp fragment. Transmission electron microscopy (TEM) of one
      representative isolate, L. garvieae RTCLI04, indicates that the isolated strain
      lacks thick outer capsule and is of KG+ (non-capsulates) phenotype. An
      intraperitoneal and intramuscular injection (2.6 * 105 CFU ml-1 ) and also
      immersion in bacterial suspension @ of 2.6 * 105 CFU ml-1 to healthy rainbow
      trout juveniles (body weight: 27.5 +/- 3.7 g) with L. garvieae RTCLI04 caused
      80%, 60% and 10% cumulative mortality in challenged fish, respectively, within 15
      days post-infection. The haemorrhagic septicaemic disease was reproduced
      experimentally. Histopathological examination of organs of experimentally
      infected fish revealed extensive degenerative and inflammatory changes in eye,
      kidney, gill and liver. PCR amplification of several putative virulence genes
      such as haemolysins, adhesins, LPxTG-containing surface proteins and adhesins
      cluster confirms the virulence of our Indian L. garvieae isolates. To the best of
      our knowledge, we are reporting for the first time that L. garvieae is associated
      with fatal haemorrhagic septicaemia in farmed rainbow trout in India.

PMID- 29473321
TI  - Reliability of autonomic and vascular components of baroreflex sensitivity in
      adolescents.
AB  - Improvements in the autonomic and vascular systems are implicated in
      cardiovascular disease risk reduction. Baroreflex sensitivity (BRS) is composed
      of vascular and autonomic components. This study aimed to investigate between-
      and within-day reliability of BRS and its autonomic and vascular determinants in
      adolescents. Thirteen male adolescents (14.1 +/- 0.5 y) participated in this
      study. For between-day reliability, participants completed four experimental
      visits separated by a minimum of 48-h. For within-day reliability, participants
      repeated BRS assessments three times in the morning with one hour between the
      measures. BRS was evaluated using the cross-spectral gain (LFgain) between blood
      pressure and heart rate interval. BRS was further divided into: 1) vascular
      component using arterial compliance (AC); and 2) autonomic component measured as
      LFgain divided by AC (LFgain/AC). LFgain, AC and LFgain/AC presented between-day
      coefficient of variation (CV) of 20%, 17%, and 20%, respectively. Similarly,
      variables associated with blood pressure control, such as cardiac output, mean
      arterial pressure, heart rate and total peripheral resistance, presented CVs
      ranging from 6% to 15%. Within-day reliability was poorer compared to between-day
      for LFgain (25%), AC (25%), and LFgain/AC (31%), as well as all hemodynamic
      variables (CVs from 11% to 22%, except heart rate with presented CV of 6%). This
      study indicates suitable between- and within-reliability of BRS and its autonomic
      and vascular determinants, as well as hemodynamic variables associated with BRS,
      in adolescents.

PMID- 29473320
TI  - Epigenetic silencing of RNF144A expression in breast cancer cells through
      promoter hypermethylation and MBD4.
AB  - Emerging evidence shows that ring finger protein 144A (RNF144A), a poorly
      characterized member of the Ring-between-Ring (RBR) family of E3 ubiquitin
      ligases, is a potential tumor suppressor gene. However, its regulatory mechanism
      in breast cancer remains undefined. Here, we report that RNF144A promoter
      contains a putative CpG island and the methylation levels of RNF144A promoter are
      higher in primary breast tumors than those in normal breast tissues.
      Consistently, RNF144A promoter methylation levels are associated with its
      transcriptional silencing in breast cancer cells, and treatment with DNA
      methylation inhibitor 5-Aza-2-deoxycytidine (AZA) reactivates RNF144A expression
      in cells with RNF144A promoter hypermethylation. Furthermore, genetic knockdown
      or pharmacological inhibition of endogenous methyl-CpG-binding domain 4 (MBD4)
      results in increased RNF144A expression. These findings suggest that RNF144A is
      epigenetically silenced in breast cancer cells by promoter hypermethylation and
      MBD4.

PMID- 29473322
TI  - A method to identify the areas at risk for the introduction of avian influenza
      virus into poultry flocks through direct contact with wild ducks.
AB  - Wild dabbling ducks are the main reservoir for avian influenza (AI) viruses and
      pose an ongoing threat to commercial poultry flocks. Combining the (i) size of
      that population, (ii) their flight distances and (iii) their AI prevalence, the
      density of AI-infected dabbling ducks (DID) was calculated as a risk factor for
      the introduction of AI viruses into poultry holdings of Emilia-Romagna region,
      Northern Italy. Data on 747 poultry holdings and on 39 AI primary outbreaks
      notified in Emilia-Romagna between 2000 and 2017 were used to validate that risk
      factor. A multivariable Bayesian logistic regression was performed to assess
      whether DID could be associated with the occurrence of AI primary outbreaks. DID
      value, being an outdoor flock, hobby poultry trading, species reared, length of
      cycle and flock size were used as explanatory variables. Being an outdoor poultry
      flock was significantly associated with a higher risk of AI outbreak occurrence.
      The probability of DID to be a risk factor for AI virus introduction was
      estimated to be 90%. A DID cut-off of 0.23 was identified to define high-risk
      areas for AI virus introduction. Using this value, the high-risk area covers 43%
      of the region. Seventy-four per cent of the primary AI outbreaks have occurred in
      that area, containing 39% of the regional poultry holdings. Poultry holdings
      located in areas with a high DID value should be included in a risk-based
      surveillance programme aimed at AI early detection.

PMID- 29473323
TI  - Adult spinal opioid receptor MU1 expression after incision is altered by early
      life repetitive tactile and noxious procedures in rats.
AB  - Clinical and experimental data suggests that noxious stimulation at critical
      stages of development results in long-term changes on nociceptive processing in
      later life. Here, we use an established, well-documented rat model of repetitive
      noxious procedures closely mimicking the clinical situation in the NICU. In order
      to understand molecular changes underlying the long-term consequences of
      repetitive stimulation of the developing nociceptive system the present study
      aims to analyze the presence of the u-opioid-receptor-1 (OPRM1). Neonatal rats
      received either four needle pricks per day in the left hind-paw from postnatal
      day 0-7 as a model of procedural pain in infancy. Control pups were handled in
      the same way but were instead tactile stimulated, or were left undisturbed. At
      the age of 8 weeks, all animals received an ipsilateral hind-paw incision as a
      model for post-operative pain, and mechanical sensitivity was tested at multiple
      time-points. Before, and 1 or 5 days post-incision, spinal cord tissue was
      collected for immunostaining of opioid receptor OPRM1. Semi-quantitative
      immunocytochemical analysis of superficial laminae in lumbar spinal dorsal horn
      revealed that: (1) early life repetitive tactile or noxious procedures do not
      alter baseline levels of OPRM1 staining intensity and (2) early life repetitive
      tactile or noxious procedures lead to a decrease in OPRM1 staining intensity 5
      days after incision in adulthood compared to undisturbed controls. We conclude
      that early life repetitive tactile or noxious procedures affect the intensity of
      OPRM1-immunoreactivity in the lumbar superficial spinal cord dorsal horn after
      adulthood injury, without affecting baseline intensity. (c) 2018 The Authors.
      Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol
      78: 417-426, 2018.

PMID- 29473325
TI  - Cheminformatics Analysis of Dynamic WNK-Inhibitor Interactions.
AB  - The With-No-Lysine (WNK) serine/threonine kinase family constitutes a unique and
      distinctive branch of the kinome. The four proteins of this family (WNK1/2/3/4)
      are involved in blood pressure regulation, body fluid, and electrolyte
      homeostasis. Herein, we modeled and analyzed the binding modes of all publicly
      available small orthosteric and allosteric binders (including WNK463 and WNK467)
      experimentally tested towards any of the WNK family member. To do so, we relied
      on state-of-the-art cheminformatics approaches including structure-based
      molecular docking and molecular dynamics simulations. In particular, we computed
      and analyzed the (i) molecular selectivity of known inhibitors when docked in the
      binding site of each WNK family member, (ii) the dynamic WNK-inhibitor
      interactions at both orthosteric and allosteric sites to derive new structure
      activity relationships, and (iii) the key specific interactions present in each
      binding site. This study reports on the first, cheminformatics-powered analysis
      of the entire chemical space of known WNK inhibitors. We discuss the conservation
      of critical WNK-inhibitor interactions and the existence of isoform-specific
      interactions that could enable the rational design of more potent and selective
      WNK binders.

PMID- 29473324
TI  - Establishment and characterization of in vivo orthotopic bioluminescent xenograft
      models from human osteosarcoma cell lines in Swiss nude and NSG mice.
AB  - Osteosarcoma is one of the most common primary bone tumors in childhood and
      adolescence. Metastases occurrence at diagnosis or during disease evolution is
      the main therapeutic challenge. New drug evaluation to improve patient survival
      requires the development of various preclinical models mimicking at best the
      complexity of the disease and its metastatic potential. We describe here the
      development and characteristics of two orthotopic bioluminescent (Luc/mKate2)
      cell-derived xenograft (CDX) models, Saos-2-B-Luc/mKate2-CDX and HOS-Luc/mKate2
      CDX, in different immune (nude and NSG mouse strains) and bone (intratibial and
      paratibial with periosteum activation) contexts. IVIS SpectrumCT system allowed
      both longitudinal computed tomography (CT) and bioluminescence real-time follow
      up of primary tumor growth and metastatic spread, which was confirmed by
      histology. The murine immune context influenced tumor engraftment, primary tumor
      growth, and metastatic spread to lungs, bone, and spleen (an unusual localization
      in humans). Engraftment in NSG mice was found superior to that found in nude mice
      and intratibial bone environment more favorable to engraftment compared to
      paratibial injection. The genetic background of the two CDX models also led to
      distinct primary tumor behavior observed on CT scan. Saos-2-B-Luc/mKate2-CDX
      showed osteocondensed, HOS-Luc/mKate2-CDX osteolytic morphology. Bioluminescence
      defined a faster growth of the primary tumor and metastases in Saos-2-B
      Luc/mKate2-CDX than in HOS-Luc/mKate2-CDX. The early detection of primary tumor
      growth and metastatic spread by bioluminescence allows an improved exploration of
      osteosarcoma disease at tumor progression, and metastatic spread, as well as the
      evaluations of anticancer treatments. Our orthotopic models with metastatic
      spread bring complementary information to other types of existing osteosarcoma
      models.

PMID- 29473326
TI  - Prediction of radiotherapy response with a 5-microRNA signature-based nomogram in
      head and neck squamous cell carcinoma.
AB  - Radiotherapy is unlikely to benefit all patients with head and neck squamous cell
      carcinoma (HNSCC). Therefore, novel method is warranted to predict the
      radiotherapy response. Our study aimed to construct a microRNA (miRNA)-based
      nomogram to predict clinical outcomes of patients with HNSCC receiving
      radiotherapy. We screened out 56 differential miRNAs by analyzing 44 paired tumor
      and adjacent normal samples miRNA expression profiles from The Cancer Genome
      Atlas (TCGA). A total of 307 patients with HNSCC receiving adjuvant radiotherapy
      were randomly divided into a training set (n = 154) and a validation set (n =
      153). In the training set, we combined the differential miRNA profiles with
      clinical outcomes, and LASSO regression model was applied to establish a 5-miRNA
      signature. The prediction accuracy of the 5-miRNA signature was further
      validated. In addition, target genes of these miRNAs were predicted, and Gene
      Ontology (GO) analysis as well as KEGG pathway analysis was executed. A 5-miRNA
      signature including miR-99a, miR-31, miR-410, miR-424, and miR-495 was
      identified. With a cutoff value of 1.2201 from Youden's index, the training set
      was divided into high-risk and low-risk groups, and the 5-year overall survival
      was significantly different (30% vs. 73%, HR 3.65, CI 2.46-8.16; P < 0.0001).
      Furthermore, our 5-miRNA signature revealed that only low-risk group would
      benefit from radiotherapy. Then, a nomogram combining 5-miRNA signature with
      clinical variables to predict radiotherapy response was constructed. The analysis
      of 108 target genes of these miRNAs revealed some potential mechanisms in HNSCC
      radiotherapy response for future investigations. In conclusion, the 5-miRNA
      signature-based nomogram is useful in predicting radiotherapy response in HNSCC
      and might become a promising tool to optimize radiation strategies.

PMID- 29473327
TI  - Epidemiological investigation of pseudorabies in Shandong Province from 2013 to
      2016.
AB  - In late 2011, a variant pseudorabies virus (vPRV) emerged in Bartha-K61
      vaccinated pig herds, resulting in high morbidity and mortality of piglets in
      China. Since 2013, the autopsy lesions, histological examinations, virus
      isolation, phylogenetic analysis and selection pressure analysis of the gE gene
      of vPRV were recorded for 395 clinical cases, and 5,033 pig serum samples were
      detected by PRV gE-coated enzyme-linked immunosorbent assay. The major clinical
      symptoms were abortion in pregnant sows, fatal neurological signs in piglets and
      respiratory disease in growing pigs. Necrotic splenitis, hepatitis and
      lymphadenitis, haemorrhagic nephritis and non-suppurative encephalitis were
      observed by histopathological examination. Typical eosinophilic inclusion bodies
      were found in the nuclei of liver cells. Using PCR, 110 samples among 395
      clinical cases tested positive for the gE gene. Fifteen vPRV strains were
      isolated and confirmed by sequencing and phylogenetic analysis of the gE gene.
      The strains shared 97.1%-99.9% nucleotide (nt) and 96.6%-99.5% amino acid (aa)
      homology with PRV reference strains. Selection pressure analysis showed that one
      site in the codons of glycoprotein E was under positive selection. Of the 5,033
      serum samples, 2,909 were positive by ELISA for a positive rate of 57.8%. These
      results showed that vPRV was still prevalent in Shandong Province, indicating
      severe PRV infectious pressure. The preparation of new vaccines against PRV is
      extremely urgent.

PMID- 29473329
TI  - Health Libraries Group Conference 2018.
AB  - It's conference time again! There is an exciting programme in prospect in this
      year's biennial Health Libraries Group (#HLG2018) conference covering key
      elements of library and information workers' daily practice. Uppermost in
      everyone's mind is the importance of ongoing personal and professional
      development with the Health Libraries Group Continuing Professional Development
      Panel putting this into practice as they host regional peer support sessions for
      presenters in the period leading up to the conference. As the official journal of
      the Health Libraries Group, the Health Information and Libraries Journal is
      similarly keen to support presenters in the practical task of translating their
      presentations into papers. Do get in touch if you would like advice on what to do
      next.

PMID- 29473328
TI  - LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the
      miR-20a-5p/HMGA2 axis in breast cancer.
AB  - To study the regulatory effect of lncRNA HOTAIR/miR-20a-5p/HMGA2 axis on breast
      cancer (BC) cell growth, cell mobility, invasiveness, and apoptosis. The
      microarray data of lncRNAs and mRNAs with differential expression in BC tissues
      were analyzed in the Cancer Genome Atlas (TCGA) database. LncRNA HOX transcript
      antisense RNA (lncRNA HOTAIR) expression in BC was assessed by qRT-PCR. Cell
      viability was confirmed using MTT and colony formation assay. Cell apoptosis was
      analyzed by TdT-mediated dUTP nick-end labeling (TUNEL) assay. Cell mobility and
      invasiveness were testified by transwell assay. RNA pull-down and dual luciferase
      assay were used for analysis of the correlation between lncRNA HOTAIR and miR-20a
      5p, as well as relationship of miR-20a-5p with high mobility group AT-hook 2
      (HMGA2). Tumor xenograft study was applied to confirm the correlation of lncRNA
      HOTAIR/miR-20a-5p/HMGA2 axis on BC development in vivo. The expression levels of
      the lncRNA HOTAIR were upregulated in BC tissues and cells. Knockdown lncRNA
      HOTAIR inhibited cell propagation and metastasis and facilitated cell apoptosis.
      MiR-20a-5p was a target of lncRNA HOTAIR and had a negative correlation with
      lncRNA HOTAIR. MiR-20a-5p overexpression in BC suppressed cell growth, mobility,
      and invasiveness and facilitated apoptosis. HMGA2 was a target of miR-20a-5p,
      which significantly induced carcinogenesis of BC. BC cells progression was
      mediated by lncRNA HOTAIR via affecting miR-20a-5p/HMGA2 in vivo. LncRNA HOTAIR
      affected cell growth, metastasis, and apoptosis via the miR-20a-5p/HMGA2 axis in
      breast cancer.

PMID- 29473330
TI  - Making information skills meaningful: a case study from occupational therapy.
AB  - The effective delivery of information literacy training can be a challenging
      process, and health library and information professionals are constantly
      innovating in this area. This article presents a case study of the BHSc (Hons)
      Occupational therapy degree programme at York St John University to demonstrate
      ways in which deep integration of information skills into the curriculum can be
      achieved. The article advises that in the delivery of health and social care
      related information skills, we should look more broadly at where relevant
      learning can happen. In particular, contexts of the health care environment are
      suggested as a consideration rather than the narrow scope of the academic,
      classroom-based environment. Examples are provided of specific teaching and
      learning activities used on the programme alongside CPD activity and curriculum
      design.

PMID- 29473332
TI  - Chromosomal abnormality variation detected by G-banding is associated with
      prognosis of diffuse large B-cell lymphoma treated by R-CHOP-based therapy.
AB  - Diffuse large B-cell lymphoma (DLBCL), which is the most prevalent disease
      subtype of non-Hodgkin lymphoma, is highly heterogeneous in terms of cytogenetic
      and molecular features. This study retrospectively investigated the clinical
      impact of G-banding-defined chromosomal abnormality on treatment outcomes of
      DLBCL in the era of rituximab-containing immunochemotherapy. Of 181 patients who
      were diagnosed with DLBCL and treated with R-CHOP or an R-CHOP-like regimen
      between January 2006 and April 2014, metaphase spreads were evaluable for G
      banding in 120. In these 120 patients, 40 were found to harbor a single
      chromosomal aberration type; 63 showed chromosomal abnormality variations (CAVs),
      which are defined by the presence of different types of chromosomal abnormalities
      in G-banding, including 19 with two CAVs and 44 with >=3 CAVs; and 17 had normal
      karyotypes. No specific chromosomal break point or numerical abnormality was
      associated with overall survival (OS) or progression-free survival (PFS), but the
      presence of >=3 CAVs was significantly associated with inferior OS rates (hazard
      ratio (HR): 2.222, 95% confidence interval (CI): 1.056-4.677, P = 0.031) and
      tended to be associated with shorter PFS (HR: 1.796, 95% CI: 0.965-3.344, P =
      0.061). In addition, >=3 CAVs more frequently accumulated in high-risk patients,
      as defined by several conventional prognostic indices, such as the revised
      International Prognostic Index. In conclusion, our results suggest that the
      emergence of more CAVs, especially >=3, based on chromosomal instability
      underlies the development of high-risk disease features and a poor prognosis in
      DLBCL.

PMID- 29473333
TI  - Risk factors and survival outcomes in patients with breast cancer and lung
      metastasis: a population-based study.
AB  - The risk factors for morbidity and mortality in breast cancer lung metastases
      (BCLM) patients still remain poorly identified. The aim of this study was to
      assess the incidence and survival of BCLM and associated risk factors. Patients
      with BCLM were identified from the Surveillance, Epidemiology, and End Results
      (SEER) database. Multivariate logistic regression analysis was used to determine
      the risk factors for BCLM. Predictors of factors associated with death were
      analyzed in Cox regression and Fine and Gray's test. Of the 11568 patients with
      stage IV breast cancer, 4213 (36.4%) had BCLM and 1214 (10.5%) had metastases
      confined to lungs. The median survival time for patients with BCLM was 21 months,
      and 15.5% of the patients were alive more than 3 years. The tumor subtype
      distribution was 45.3% HR- /HER2- , 12.2% HR+ /HER2+ , 7.8% HR- /HER2+, and 15.0%
      triple-negative subtype. Compared with patients without BCLM, those with BCLM
      were more likely to be aged, female, black, higher tumor grade, HR- /HER2+ , HR+
      /HER2+, and triple-negative subtypes at diagnosis. Survival analysis showed that
      the aged, black race, HR- /HER2+ , triple-negative subtype, higher grade were the
      independent risk factor for BCLM patients' survival, while HR+ /HER2+ subtype,
      insured status, and married status suggested better prognosis. In conclusion, the
      incidence and prognosis of BCLM varied by tumor subtypes, age, and race. Elderly
      patients with HER2-positive or triple-negative tumors were more likely to have
      BCLM.

PMID- 29473334
TI  - Treatment-related mortality in newly diagnosed pediatric cancer: a population
      based analysis.
AB  - Using a previously developed reliable and valid treatment-related mortality (TRM)
      definition, our objective was to describe the proportion of children newly
      diagnosed with cancer experiencing TRM and to identify risk factors for TRM in a
      population-based cohort. We included children with cancer <19 years diagnosed and
      treated in Ontario who were diagnosed between 2003 and 2012. Children with cancer
      were identified using data in a provincial registry. Cumulative incidence of TRM
      was calculated where progressive disease death was considered a competing event.
      Among the 5179 children included, 179 had TRM, 478 died of progressive disease,
      and 4522 were still alive. At 5 years, the cumulative incidence of TRM among the
      entire cohort was 3.9% (95% confidence interval (CI) 3.3-4.5%). When compared to
      brain tumor patients, leukemia and lymphoma patients had a significantly higher
      risk of TRM (hazard ratio (HR) 2.5, 95% CI: 1.6-4.0; P < 0.0001). Infants were at
      significantly higher risk of TRM across diagnostic groups. Other factors
      associated with higher risks of TRM were metastatic disease (P < 0.0001),
      diagnosis prior to 1 January 2008 (P = 0.001), hematopoietic stem cell
      transplantation (HSCT) (P < 0.0001), and relapse (P < 0.0001). The 5-year
      cumulative incidence of TRM was 3.9% among newly diagnosed children with cancer.
      Infants were at higher risk of TRM across diagnostic groups. Other risk factors
      for TRM were leukemia or lymphoma, metastatic disease, earlier diagnosis year,
      HSCT, and relapse. Future work should further refine prognostic factors by
      specific cancer diagnosis to best understand when and how to intervene to improve
      outcomes.

PMID- 29473335
TI  - Leptomeningeal enhancement on preoperative brain MRI in patients with
      glioblastoma and its clinical impact.
AB  - AIM: Leptomeningeal enhancement (LME) on preoperative brain magnetic resonance
      imaging (MRI) does not always indicate leptomeningeal seeding (LMS). With Stupp's
      regimen, authors have treated glioblastoma patients with LME on preoperative
      brain MRI but here we tried to find the clinical impact of LME. METHODS: From
      2005 to 2015, 290 patients with glioblastoma have been treated with Stupp's
      regimen at Samsung Medical Center. Among these, 33 patients showed LME on
      preoperative brain MRI. We compared the clinical outcomes between the patients
      with or without LME on preoperative brain MRI and analyzed the clinical results
      according to changes of LME at following MRI. RESULTS: The median survival was 23
      months, and 2-year overall survival (OS) and disease-free survival (DFS) rate was
      46.3% and 19.6%, respectively. Prognostic factors for OS and DFS were Karnofsky
      performance status, extent of resection and adjuvant chemotherapy. MGMT promoter
      methylation status was a significant prognostic factor for DFS. However, LME was
      not a significant prognostic factor for OS (P = 0.156) or DFS (P = 0.193). Among
      the 33 patients with LME on preoperative MRI, 21 (63.6%) showed persistent LME at
      the next MRI. A statistically significant difference in 2-year survival was
      evident between patients with and without persistent LME (OS, 17.3% and 70.1%,
      respectively, P = 0.044; DFS, 5.3% and 54.0%, respectively, P = 0.006). The most
      common pattern of failure was local recurrence. However, patients with persistent
      LME displayed a higher incidence of LMS than patients without LME. CONCLUSION:
      LME on preoperative brain MRI did not affect the clinical results in glioblastoma
      patients treated with the Stupp's regimen. However, persistence of LME was
      associated with poor survival and high possibility of LMS. For these patients,
      the postoperative adjuvant treatment should focus on palliative aim or more
      aggressive treatment scheme should be followed to overcome the disastrous
      results.

PMID- 29473336
TI  - Large-Scale Direct-Writing of Aligned Nanofibers for Flexible Electronics.
AB  - Nanofibers/nanowires usually exhibit exceptionally low flexural rigidities and
      remarkable tolerance against mechanical bending, showing superior advantages in
      flexible electronics applications. Electrospinning is regarded as a powerful
      process for this 1D nanostructure; however, it can only be able to produce
      chaotic fibers that are incompatible with the well-patterned microstructures in
      flexible electronics. Electro-hydrodynamic (EHD) direct-writing technology
      enables large-scale deposition of highly aligned nanofibers in an additive,
      noncontact, real-time adjustment, and individual control manner on rigid or
      flexible, planar or curved substrates, making it rather attractive in the
      fabrication of flexible electronics. In this Review, the ground-breaking research
      progress in the field of EHD direct-writing technology is summarized, including a
      brief chronology of EHD direct-writing techniques, basic principles and alignment
      strategies, and applications in flexible electronics. Finally, future prospects
      are suggested to advance flexible electronics based on orderly arranged EHD
      direct-written fibers. This technology overcomes the limitations of the
      resolution of fabrication and viscosity of ink of conventional inkjet printing,
      and represents major advances in manufacturing of flexible electronics.

PMID- 29473337
TI  - Acoustic radiation force impulse of the liver after Fontan operation: Correlation
      with cardiopulmonary exercise test.
AB  - BACKGROUND: The current management paradigm for children with single ventricle
      heart disease involves a series of palliative surgeries, culminating in the
      Fontan operation. This physiology results in a high central venous pressure, and
      in the setting of single ventricle heart disease, results in hepatic injury and
      fibrosis over time. Fontan-associated liver disease (FALD) is universally present
      in this cohort, and the current gold standard for diagnosis remains biopsy.
      Noninvasive assessments of liver fibrosis, such as ultrasound with elastography
      or acoustic radiation force impulse (ARFI), has been utilized in this cohort. The
      effect of poor cardiovascular efficiency, as measured by cardiopulmonary exercise
      test (CPET), on assessments of liver fibrosis remains poorly understood. METHODS:
      Retrospective, cross-sectional study. Subjects were evaluated in a
      multidisciplinary clinic setting for patients who have undergone Fontan
      operation. CPETs, liver ultrasound with elastography (ARFI), and standard
      laboratory tests were performed as part of routine clinical care pathway.
      Statistical analysis included linear correlation. RESULTS: There was a poor
      correlation between mean ARFI velocity and peak oxygen consumption (VO2max ) in
      this cohort (r = .20, P = NS). Similarly, there was poor correlation between ARFI
      and biomarkers of liver injury, time since Fontan operation and Fontan pressure.
      DISCUSSION: ARFI had poor correlation with functional capacity after Fontan, as
      measured by VO2max obtained during CPET. While a single measurement of liver
      elastography was not associated with cardiopulmonary efficiency, longitudinal
      data may reveal an association.

PMID- 29473339
TI  - Feeling of incomplete emptying with little post-void residual in patients with
      lower urinary tract symptoms: Clinical implications and treatment outcomes.
AB  - OBJECTIVE: The aim of the present study was to examine the clinical features and
      implications of a feeling of incomplete emptying despite little post-void
      residual (PVR), because it remains unclear why patients are bothered by such an
      undefined feeling. METHODS: Data were collected prospectively from 173
      consecutive patients (135 men, 38 women) with a complaint of a feeling of
      incomplete emptying with PVR <50 mL at an initial visit. The International
      Prostate Symptom Score (IPSS), quality of life (QoL) score, overactive bladder
      symptom score (OABSS), prostate volume, and PVR were determined. Subjective
      symptoms were re-evaluated after 8 weeks of medication for co-occurring urinary
      symptoms. RESULTS: Most patients presented with high scores for a feeling of
      incomplete emptying, determined by Item 1 on the IPSS. The score for a feeling of
      incomplete emptying was positively correlated with all IPSS-related scores. Men
      with a feeling of incomplete emptying more often had co-occurring voiding
      symptoms with higher scores than women. Significant symptom relief was achieved
      for a feeling of incomplete emptying as well as voiding and storage symptoms
      after treatment. In men, there was a positive correlation between the extent of
      symptom relief of a feeling of incomplete emptying and voiding symptoms.
      CONCLUSIONS: A feeling of incomplete emptying with little PVR is frequently
      observed in routine clinical practice in both men and women, along with voiding
      and storage symptoms. This feeling was simultaneously improved by medications for
      co-occurring urinary symptoms.

PMID- 29473338
TI  - The current state and future perspectives of cannabinoids in cancer biology.
AB  - To date, cannabinoids have been allowed in the palliative medicine due to their
      analgesic and antiemetic effects, but increasing number of preclinical studies
      indicates their anticancer properties. Cannabinoids exhibit their action by a
      modulation of the signaling pathways crucial in the control of cell proliferation
      and survival. Many in vitro and in vivo experiments have shown that cannabinoids
      inhibit proliferation of cancer cells, stimulate autophagy and apoptosis, and
      have also a potential to inhibit angiogenesis and metastasis. In this review, we
      present an actual state of knowledge regarding molecular mechanisms of
      cannabinoids' anticancer action, but we discuss also aspects that are still not
      fully understood such as the role of the endocannabinoid system in a
      carcinogenesis, the impact of cannabinoids on the immune system in the context of
      cancer development, or the cases of a stimulation of cancer cells' proliferation
      by cannabinoids. The review includes also a summary of currently ongoing clinical
      trials evaluating the safety and efficacy of cannabinoids as anticancer agents.

PMID- 29473340
TI  - A nomogram incorporating six easily obtained parameters to discriminate
      intrahepatic cholangiocarcinoma and hepatocellular carcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the
      most prevalent histologic types of primary liver cancer (PLC). Although ICC and
      HCC share similar risk factors and clinical manifestations, ICC usually bears
      poorer prognosis than HCC. Confidently discriminating ICC and HCC before surgery
      is beneficial to both treatment and prognosis. Given the lack of effective
      differential diagnosis biomarkers and methods, construction of models based on
      available clinicopathological characteristics is in need. Nomograms present a
      simple and efficient way to make a discrimination. A total of 2894 patients who
      underwent surgery for PLC were collected. Of these, 1614 patients formed the
      training cohort for nomogram construction, and thereafter, 1280 patients formed
      the validation cohort to confirm the model's performance. Histopathologically
      confirmed ICC was diagnosed in 401 (24.8%) and 296 (23.1%) patients in these two
      cohorts, respectively. A nomogram integrating six easily obtained variables
      (Gender, Hepatitis B surface antigen, Aspartate aminotransferase, Alpha
      fetoprotein, Carcinoembryonic antigen, Carbohydrate antigen 19-9) is proposed in
      accordance with Akaike's Information Criterion (AIC). A score of 15 was
      determined as the cut-off value, and the corresponding discrimination efficacy
      was sufficient. Additionally, patients who scored higher than 15 suffered poorer
      prognosis than those with lower scores, regardless of the subtype of PLC. A
      nomogram for clinical discrimination of ICC and HCC has been established, where a
      higher score indicates ICC and poor prognosis. Further application of this
      nomogram in multicenter investigations may confirm the practicality of this tool
      for future clinical use.

PMID- 29473341
TI  - Expression and copy number gains of the RET gene in 631 early and mid stage non
      small cell lung cancer cases.
AB  - BACKGROUND: To identify whether RET is a potential target for NSCLC treatment, we
      examined the status of the RET gene in 631 early and mid stage NSCLC cases from
      south central China. METHODS: RET expression was identified by Western blot. RET
      positive expression samples were verified by immunohistochemistry. RET gene
      mutation, copy number variation, and rearrangement were analyzed by DNA Sanger
      sequencing, TaqMan copy number assays, and reverse transcription-PCR. ALK and
      ROS1 expression levels were tested by Western blot and EGFR mutation using Sanger
      sequencing. RESULTS: The RET-positive rate was 2.5% (16/631). RET-positive
      expression was related to poorer tumor differentiation (P < 0.05). In the 16 RET
      positive samples, only two samples of moderately and poorly differentiated lung
      adenocarcinomas displayed RET rearrangement, both in RET-KIF5B fusion partners.
      Neither ALK nor ROS1 translocation was found. The EGFR mutation rate in RET
      positive samples was significantly lower than in RET-negative samples (P < 0.05).
      CONCLUSION: RET-positive expression in early and mid stage NSCLC cases from south
      central China is relatively low and is related to poorer tumor differentiation.
      RET gene alterations (copy number gain and rearrangement) exist in all RET
      positive samples. RET-positive expression is a relatively independent factor in
      NSCLC patients, which indicates that the RET gene may be a novel target site for
      personalized treatment of NSCLC.

PMID- 29473342
TI  - Clofarabine exerts antileukemic activity against cytarabine-resistant B-cell
      precursor acute lymphoblastic leukemia with low deoxycytidine kinase expression.
AB  - Cytosine arabinoside (Ara-C) is one of the key drugs for the treatment of acute
      myeloid leukemia. It is also used for consolidation therapy of acute
      lymphoblastic leukemia (ALL). Ara-C is a deoxyadenosine analog and is
      phosphorylated to form cytosine arabinoside triphosphate (Ara-CTP) as an active
      form. In the first step of the metabolic pathway, Ara-C is phosphorylated to Ara
      CMP by deoxycytidine kinase (DCK). However, the current cumulative evidence in
      the association of the Ara-C sensitivity in ALL appears inconclusive. We analyzed
      various cell lines for the possible involvement of DCK in the sensitivities of B
      cell precursor ALL (BCP-ALL) to Ara-C. Higher DCK expression was associated with
      higher Ara-C sensitivity. DCK knockout by genome editing with a CRISPR-Cas9
      system in an Ara-C-sensitive-ALL cell line induced marked resistance to Ara-C,
      but not to vincristine and daunorubicin, indicating the involvement of DCK
      expression in the Ara-C sensitivity of BCP-ALL. DCK gene silencing due to the
      hypermethylation of a CpG island and reduced DCK activity due to a nonsynonymous
      variant allele were not associated with Ara-C sensitivity. Clofarabine is a
      second-generation deoxyadenosine analog rationally synthesized to improve
      stability and reduce toxicity. The IC50 of clofarabine in 79 BCP-ALL cell lines
      was approximately 20 times lower than that of Ara-C. In contrast to Ara-C,
      although the knockout of DCK induced marked resistance to clofarabine,
      sensitivity to clofarabine was only marginally associated with DCK gene
      expression level, suggesting a possible efficacy of clofarabine for BCP-ALL that
      shows relative Ara-C resistance due to low DCK expression.

PMID- 29473344
TI  - Employment benefits and job retention: evidence among patients with colorectal
      cancer.
AB  - A "health shock," that is, a large, unanticipated adverse health event, can have
      long-term financial implications for patients and their families. Colorectal
      cancer is the third most commonly diagnosed cancer among men and women and is an
      example of a specific health shock. We examined whether specific benefits
      (employer-based health insurance, paid sick leave, extended sick leave, unpaid
      time off, disability benefits) are associated with job retention after diagnosis
      and treatment of colorectal cancer. In 2011-14, we surveyed patients with Stage
      III colorectal cancer from two representative SEER registries. The final sample
      was 1301 patients (68% survey response rate). For this study, we excluded 735
      respondents who were not employed and 20 with unknown employment status. The
      final analytic sample included 546 respondents. Job retention in the year
      following diagnosis was assessed, and multivariable logistic regression was used
      to evaluate associations between job retention and access to specific employment
      benefits. Employer-based health insurance (OR = 2.97; 95% CI = 1.56-6.01; P =
      0.003) and paid sick leave (OR = 2.93; 95% CI = 1.23-6.98; P = 0.015) were
      significantly associated with job retention, after adjusting for
      sociodemographic, clinical, geographic, and job characteristics.

PMID- 29473343
TI  - Central nervous system relapse in patients over 80 years with diffuse large B
      cell lymphoma: an analysis of two LYSA studies.
AB  - CNS relapse is reported in 2-5% of diffuse large B-cell lymphoma (DLBCL)
      patients, dramatically decreasing overall survival (OS). Very few studies address
      incidence and risk factors of CNS relapse in very elderly patients, a challenging
      population to treat given their commonly associated comorbidities. A
      retrospective analysis was performed of 270 DLBCL patients >80 years treated
      between 2004 and 2013 in two multicentre phase II LYSA trials (LNH03-7B, LNH09
      7B) evaluating the addition of rituximab or ofatumumab to mini-CHOP as front-line
      therapy. No patients received CNS prophylaxis. CNS relapse was evaluated
      according to cumulative incidence, patient characteristics, risk factors, and
      survival. Median age was 83 years (range: 79-95). After a median follow-up of
      28.7 months, eight patients had CNS relapse (3.0%). Median time between inclusion
      and CNS relapse was 19.2 months (range: 3.2-32.6). Patients survived a median of
      1.5 months after CNS relapse (range: 0.4-4.1). Median OS from relapse was
      significantly lower in CNS relapse patients (1.5 months, 95% CI: 0.4-3.5)
      compared to patients with non-CNS relapse (6.6 months; 95% CI: 4.6-11.9). No
      baseline characteristics were associated with CNS relapse. The proportion of
      patients with CNS disease did not differ significantly between patients with low
      intermediate risk according to CNS-IPI and patients with high risk (3% vs. 2.8%,
      P = 1.00). CNS relapse cumulative incidence in very elderly treatment-naive
      patients is 1.8% at 2 years and is associated with poor survival. This population
      had a long median time to CNS relapse. Absence of prophylaxis did not strongly
      impact CNS relapse incidence.

PMID- 29473345
TI  - CGB5 expression is independently associated with poor overall survival and
      recurrence-free survival in patients with advanced gastric cancer.
AB  - The human CGB5 gene encodes chorionic gonadotropin (hCG)beta 5, which is
      aberrantly expressed in trophoblastic neoplasm and in some non-trophoblastic
      neoplasms. Fucntional studies observed that it involved tumor initiation, growth,
      and metastatic outgrowth. In this study, using data from the International Cancer
      Genome Consortium (ICGC) and the Cancer Genome Atlas (TCGA)-stomach
      adenocarcinoma (STAD), we assessed the independent prognostic value of CGB5
      expression in patients with primary gastric cancer (GC). Results showed that CGB5
      expression was nearly not expressed in normal GC tissues. In comparison, its
      expression was detected in 214 of the 415 primary GC cases (51.6%) in TCGA-STAD
      and was associated with poor response to primary therapy and a higher risk of
      recurrence and death. In early stages, CGB5 expression was not a prognostic
      factor in terms of OS (HR: 1.448; 95% CI: 0.811-2.588, P = 0.211) or RFS (HR:
      1.659; 95% CI: 0.778-3.540, P = 0.190). However, its expression was independently
      associated with unfavorable OS (HR: 1.719; 95% CI: 1.115-2.651, P = 0.014) and
      RFS (HR: 3.602; 95% CI: 1.708-7.598, P = 0.001) in advanced stages. Using deep
      sequencing data from TCGA-STAD, we found that CGB5 expression was not related to
      its genetic amplification or DNA methylation in GC. Based on these findings, we
      infer that CGB5 expression is common in GC patients and its expression might
      independently predict poor OS and RFS in advanced stages, but not in early stages
      of GC.

PMID- 29473347
TI  - Retinal Vascular Diseases in the Asia-Pacific: Shifting Paradigms for Management.

PMID- 29473346
TI  - Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with
      Functionally Integrated Three-Dimensional Microenvironments.
AB  - Despite advances in ex vivo expansion of cord blood-derived hematopoietic
      stem/progenitor cells (CB-HSPC), challenges still remain regarding the ability to
      obtain, from a single unit, sufficient numbers of cells to treat an adolescent or
      adult patient. We and others have shown that CB-HSPC can be expanded ex vivo in
      two-dimensional (2D) cultures, but the absolute percentage of the more primitive
      stem cells decreases with time. During development, the fetal liver is the main
      site of HSPC expansion. Therefore, here we investigated, in vitro, the outcome of
      interactions of primitive HSPC with surrogate fetal liver environments. We
      compared bioengineered liver constructs made from a natural three-dimensional
      liver-extracellular-matrix (3D-ECM) seeded with hepatoblasts, fetal liver-derived
      (LvSt), or bone marrow-derived stromal cells, to their respective 2D culture
      counterparts. We showed that the inclusion of cellular components within the 3D
      ECM scaffolds was necessary for maintenance of HSPC viability in culture, and
      that irrespective of the microenvironment used, the 3D-ECM structures led to the
      maintenance of a more primitive subpopulation of HSPC, as determined by flow
      cytometry and colony forming assays. In addition, we showed that the timing and
      extent of expansion depends upon the biological component used, with LvSt
      providing the optimal balance between preservation of primitive CB HSPC and
      cellular differentiation. Stem Cells Translational Medicine 2018;7:271-282.

PMID- 29473348
TI  - Cone-beam x-ray luminescence computed tomography based on x-ray absorption
      dosage.
AB  - With the advances of x-ray excitable nanophosphors, x-ray luminescence computed
      tomography (XLCT) has become a promising hybrid imaging modality. In particular,
      a cone-beam XLCT (CB-XLCT) system has demonstrated its potential in in vivo
      imaging with the advantage of fast imaging speed over other XLCT systems.
      Currently, the imaging models of most XLCT systems assume that nanophosphors emit
      light based on the intensity distribution of x-ray within the object, not
      completely reflecting the nature of the x-ray excitation process. To improve the
      imaging quality of CB-XLCT, an imaging model that adopts an excitation model of
      nanophosphors based on x-ray absorption dosage is proposed in this study. To
      solve the ill-posed inverse problem, a reconstruction algorithm that combines the
      adaptive Tikhonov regularization method with the imaging model is implemented for
      CB-XLCT reconstruction. Numerical simulations and phantom experiments indicate
      that compared with the traditional forward model based on x-ray intensity, the
      proposed dose-based model could improve the image quality of CB-XLCT
      significantly in terms of target shape, localization accuracy, and image
      contrast. In addition, the proposed model behaves better in distinguishing closer
      targets, demonstrating its advantage in improving spatial resolution.

PMID- 29473349
TI  - Benchtop and animal validation of a portable fluorescence microscopic imaging
      system for potential use in cholecystectomy.
AB  - We propose a portable fluorescence microscopic imaging system (PFMS) for
      intraoperative display of biliary structure and prevention of iatrogenic injuries
      during cholecystectomy. The system consists of a light source module, a camera
      module, and a Raspberry Pi computer with an LCD. Indocyanine green (ICG) is used
      as a fluorescent contrast agent for experimental validation of the system.
      Fluorescence intensities of the ICG aqueous solution at different concentration
      levels are acquired by our PFMS and compared with those of a commercial Xenogen
      IVIS system. We study the fluorescence detection depth by superposing different
      thicknesses of chicken breast on an ICG-loaded agar phantom. We verify the
      technical feasibility for identifying potential iatrogenic injury in
      cholecystectomy using a rat model in vivo. The proposed PFMS system is portable,
      inexpensive, and suitable for deployment in resource-limited settings.

PMID- 29473350
TI  - Optical coherence tomography for the diagnosis of malignant skin tumors: a meta
      analysis.
AB  - Optical coherence tomography (OCT) is an emergent imaging tool used for
      noninvasive diagnosis of skin diseases. The present meta-analysis was carried out
      to assess the accuracy of OCT for the diagnosis of skin cancer. We conducted a
      systematic literature search though EMBASE, Medline, PubMed, the Cochrane
      Library, and Web of Science database for relevant articles published up to June
      6, 2017. The quality of the included studies was assessed using the QUADAS-2 tool
      and the Oxford Levels of Evidence Scale. Statistical analyses were conducted
      using the software Meta-Disc version 1.4 and STATA version 12.0. A total of 14
      studies involving more than 813 patients with a total of 1958 lesions were
      included in our analyses. The pooled sensitivity and specificity of OCT for skin
      cancer diagnoses were 91.8% and 86.7%, respectively. Subgroup analysis showed
      that the pooled sensitivities of OCT for detecting basal cell carcinoma (BCC),
      squamous cell carcinoma (SCC), actinic keratosis, and malignant melanoma were
      92.4%, 92.3%, 73.8%, and 81.0%, respectively. The pooled specificities were
      86.9%, 99.5%, 91.5%, and 93.8%, respectively. OCT appears to be useful for the
      detection of BCC and SCC. It is a valuable diagnostic method when screening for
      early skin cancers.

PMID- 29473351
TI  - [Clinical study of electroacupuncture with different frequencies at Lianquan (CV
      23) and Fengfu (GV 16) for stroke dysphagia].
AB  - OBJECTIVE: To observe the effects of electroacupuncture (EA) with different
      frequencies based on the western conventional treatment and rehabilita tion
      training for stroke dysphagia. METHODS: Sixty patients with dysphagia after
      stroke were randomized assigned into a low frequency (2 Hz) group and a high
      frequency (100 Hz) group, 30 cases in each one. Basic treatment was applied in
      the two groups. The acupoints were Fengfu (GV 16) and Lianquan (CV 23). EA with
      continuous wave and tolerant intensity were connected for 30 min, once a day for
      14 days. The main index was video fluoroscopic swallowing study (VFSS) to detect
      passing time at oral stage, pharynx delay time at pharyngeal stage, passing time
      at pharynx stage. The second indexes were water swallow test rating and
      standardized swallowing assessment (SSA). The clinical effect was evaluated.
      RESULTS: After treatment, the passing time at oral stage, pharynx delay time at
      pharyngeal stage, passing time at pharynx stage were lower than those before
      treatment in the two groups (all P <0.05), and the results in the low frequency
      group were better (all P <0.05). After treatment, the water swallow test rating
      improved in the two groups (both P<0.05), and that in the low frequency group was
      better (P<0.05). The SSA score decreased in the two groups (both P<0.05), and the
      improvement in the lower frequency group was superior to that in the high
      frequency group (P<0.05). The total effective rate in the low frequency group was
      93.3% (28/30), which was better than 66.7% (20/30) in the high frequency group
      (P<0.05). . CONCLUSION: The effect of EA with lower frequency is better than that
      of EA with higher frequency for stroke dysphagia.

PMID- 29473352
TI  - [Effects of pricking and cupping combined with rehabilitation training on elbow
      flexion spasticity of upper limb after stroke and its IEMG value].
AB  - OBJECTIVE: Based on rehabilitation training, to observe the clinical effect
      difference between pricking combined with cupping and western medication for
      elbow flexion spasticity of upper limb of stroke patients. METHODS: Sixty
      patients were randomly assigned by SPSS software random number generator into a
      comprehension group and a western medication group, 30 cases in each one.
      Rehabilitation was used in the two groups. Pricking and cupping were applied at
      the affected abdominal center of biceps brachii muscle on Tuesday and Friday
      continuously for 4 weeks in the comprehensive group. Baclofen was prescribed
      orally continuously for 4 weeks, once 10 mg and 3 times a day in the western
      medication group. The indexes were observed before and after 4-week treatment as
      well as at immediate treatment, immediately after the first treatment in the
      comprehension group and 24 h after treatment in the western medication group,
      including the affected elbow joint activity, modified Ashworth scale (MAS),
      simple Fugl-Meyer assessment (FMA), integrated electromyogram (IEMG) of the
      affected biceps brachii and triceps brachii. The clinical effects were evaluated.
      RESULTS: After treatment, the elbow joint activity in the two groups was improved
      compared with that before treatment (both P <0.05), with better result in the
      comprehension group (P <0.05). There was no statistical significance for MAS and
      FMA scores at immediate treatment between the two groups (both P >0.05). After
      treatment, the MAS score decreased and the FMA score increased in the two groups
      (both P<0.05), with better results in the comprehension group (both P <0.05). At
      immediate treatment and after treatment, biceps brachii IEMG decreased in the two
      groups (all P <0.05). The biceps brachii IEMG in the comprehension group at the
      immediate treatment was higher and that after treatment was lower compared with
      those in the western medication group (both P <0.05). The triceps brachii IEMG at
      immediate treatment was not statistically different from that before treatment in
      the comprehension group (P >0.05) and that in the western medication group
      decreased (P<0.05). After treatment, the triceps brachii IEMG increased in the
      two groups (both P <0.05), with higher IEMG in the comprehension group (P <0.05).
      The total effective rate was 83.3% (25/30) in the comprehensive group, which was
      higher than 60.0% (18/30) in the western medication group (P <0.05). .
      CONCLUSION: Pricking and cupping combined with rehabilitation training can reduce
      the IEMG of the biceps brachii muscle in patients with stroke, and improve the
      spasticity and motor function.

PMID- 29473353
TI  - [Acupuncture at five mind points combined with modified kidney qi decoction for
      vascular dementia of kidney essence deficiency].
AB  - OBJECTIVE: To observe the effects for vascular dementia (VD) of kidney essence
      deficiency among acupuncture at five mind points combined with modified kidney qi
      decoction, simple acupuncture at five mind points and simple modified kidney qi
      decoction. METHODS: A total of 180 VD patients were randomly assigned into a
      combination group, an acupuncture group and a herb group, 60 cases in each one.
      The conventional western medication and rehabilitation training were for all the
      patients. The modified kidney qi decoction was used in the herb group;
      acupuncture at Baihui (GV 20) and Sishencong (EX-HN 1) was applied in the
      acupuncture group; the above two methods were for the cases in the combination
      group. Acupuncture was used for 7 courses, twice a day, and 5 days as a course.
      The hasegawa dementia scale (HDS), the brief screening scale for dementia (BSSD)
      and the mini-mental state examination (MMSE) were applied before and after
      treatment. The serum superoxide dismutase (SOD), calcitonin gene-related peptide
      (CGRP) and lipid peroxidation (LPO) were detected before and after treatment. The
      effects were evaluated. RESULTS: The total effective rate of the combination
      group was 91.7% (55/60), which was better than 68.3% (41/60) in the herb group
      and 78.3% (47/60) in the acupuncture group (both P<0.05). After treatment, the
      scores of HDS, BSSD and MMSE were higher than those before treatment in the three
      groups (all P<0.05), and the scores in the combination group were superior to
      those in the other two groups (all P<0.05). SOD and CGRP increased and LPO
      decreased after treatment in the three groups (all P<0.05), and the results in
      the combination group were better (all P<0.05). . CONCLUSION: Acupuncture at five
      mind points combined with modified kidney qi decoction for VD is better than
      simple five mind acupuncture and simple modified kidney qi decoction.

PMID- 29473354
TI  - [Clinical observation on severe acute pancreatitis treated with
      electroacupuncture at Dachangshu (BL 25) and Shangjuxu (ST 37) combined with
      ulinastatin].
AB  - OBJECTIVE: To observe the clinical therapeutic effects on severe acute
      pancreatitis (SAP) treated with electroacupuncture (EA), sparse-dense wave and 2
      Hz/15 Hz, at Dachangshu (BL 25) and Shangjuxu (ST 37) assisting ulinastetin and
      explore the effective therapeutic method for SAP. METHODS: A total of 120
      patients of SAP were randomized into an observation group and a control group, 60
      cases in each one. In the control group, the routine western medicine was adopted
      with the intravenous drip with ulinastatin. In the observation group, on the
      basis of the treatment as the control group, EA was applied at Dachangshu (BL 25)
      and Shangjuxu (ST 37). The treatment was given once every day, 20 min each time.
      The treatment was 2 weeks in the two groups. The recovery time of defecation, the
      recovery time of bowel sound, the remission time of abdominal pain and the
      hospitalization time were recorded in the patients of the two groups. The changes
      in the tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and amylase,
      as well as the scores in the acute physiology and chronic health evaluation II
      (APACHE II) were compared in the patients of the two groups before treatment, and
      on the 3rd, 8th and 14th days of treatment. The therapeutic effects, the cases of
      surgical transfer or the cases of the transfer of intensive care unit (ICU) were
      compared between the two groups. RESULTS: The recovery time of defecation, the
      recovery time of bowel sound and the remission time of abdominal pain, as well as
      the hospitalization time in the observation group were shorter than those in the
      control group (all P <0.05). The levels of TNF-alpha, IL-6 and amylase, as well
      as the scores of APACHE II on the 3rd, 8th and 14th days of treatment were all
      reduced as compared with those before treatment in the two groups (all P <0.05).
      The results in the observation group were lower than those in the control group
      (all P <0.05). The total effective rate was 95.0% (57/60) in the observation
      group, better than 81.7% (49/60) in the control group (P <0.05). There were 1
      case of surgical transfer and 0 case in ICU transfer in the observation group, 3
      cases of surgical transfer and 2 cases in ICU transfer in the control group,
      indicating the significant differences between the two groups (both P <0.05). .
      CONCLUSION: EA at Dachangshu (BL 25) and Shangjuxu (ST 37) displays the
      satisfactory accessory therapeutic effects on SAP treated with ulinastatin.

PMID- 29473355
TI  - [Clinical research of vasospasm and vagus reflex during radial artery puncture
      treated with auricular point sticking].
AB  - OBJECTIVE: To evaluate the effect and clinical value of auricular point sticking
      for the diagnosis and treatment of vasospasm and vagus reflex during radial
      artery puncture, including radial artery spasm (RAS) and coronary artery spasm
      (CAS). METHODS: A total of 480 patients were randomized into an observation group
      (224 cases) and a control group (256 cases). Percutaneous coronary intervention
      and usual care in perioperative period were used in the control group. Auricular
      point sticking was began to apply 12 h before percutaneous coronary intervention
      in the observation group at Jiaogan (AH6a), Shenmen (TF4), Pizhixia (AT4),
      Neifenmi (CO18), Xin (CO15), Shen (CO10), Shenshangxian (TG2p), 1 min a time
      every point, once every 2 h, 12 h before and after operation. The incidences of
      vasospasm and vagus reflex during piercing process were compared, and the usage
      ratios of vasoactive agent were recorded, including glyceryl trinitrate, dopamine
      and atropine injections. RESULTS: The incidence of angiospasm was 4.9% (11/224)
      in the observation group, which was lower than 13.3% (34/256) in the control
      group (P<0.01). The incidence of vagal reflex of the observation group was 7.1%
      (16/224), which was lower than 19.5% (50/256) of the control group (P<0.01). The
      usage ratios of glyceryl trinitrate, atropine and dopamine injections were 3.6%
      (8/224), 7.1% (16/224), 6.3% (14/224) respectively in the observation group,
      which were lower than 14.8% (38/256), 15.6% (40/256), 15.2% (39/256) in the
      control group (all P<0.01). . CONCLUSION: Auricular point sticking achieves
      effect for the diagnosis and treatment of vasospasm and vagus reflex during
      radial artery puncture.

PMID- 29473356
TI  - [Study of optimal parameters of scalp electroacupuncture for rehabilitation
      effect on children of cerebral palsy].
AB  - OBJECTIVE: To analyze the effect difference of wave, intensity, time and
      treatment frequency by orthogonal design so as to explore the optimal parameters
      of scalp electroacupuncture (EA) for rehabilitation effect on children of
      cerebral palsy. METHODS: Ninety children of cerebral palsy were assigned into 9
      groups by orthogonal design, 10 cases in each one. The acupoints were bilateral
      excitable area, foot motor sensory area, speech two area, speech three area,
      balance area, and intelligent nine acupoints, including Shenting (GV 24),
      Sishencong (EX-HN 1), and bilateral Benshen (GB 13) and Touwei (ST 8). EA was
      applied at bilateral excitable area and speech three area. We designed an
      orthogonal experiment with four factors and three levels. We studied wave (sparse
      wave of 2 Hz, density wave of 100 Hz, sparse and density wave of 2 Hz /100 Hz),
      intensity (1 mA, 2 mA, intensity based on tolerance), time (10 min, 20 min, 30
      min), frequency (once a day, once every other day, twice a week). The Gesell
      developmental scale was used to evaluate the developmental quotient (DQ); and
      gross motor function measure (GMFM), motor function before and after treatment.
      RESULTS: The optimal parameters for DQ and GMFM were 2 Hz/100 Hz, 20 min, once
      every other day. . CONCLUSION: The optimal parameters for cerebral palsy may be 2
      Hz/100 Hz, 20 min, once every other day.

PMID- 29473357
TI  - [Clinical observation of Zheng's stunt needling technique in the treatment of
      juvenile myopia].
AB  - OBJECTIVE: To compare the differences in the clinical therapeutic effects on
      juvenile myopia between Zheng's stunt needling technique and traditional even
      needling technique. METHODS: A total of 166 cases of mild juvenile myopia
      (diopter <-3.00D) were randomized into an observation group (Zheng's stunt
      needling technique) and a control group (traditional even needling technique), 83
      cases in each one (166 affected eyes). Taiyang (EX-HN 5), Fengchi (GB 20),
      Cuanzhu (BL 2), Hegu (LI 4) and Guangming (GB 37) were used in the two groups. In
      the observation group, the erlongxizhu needling technique was adopted at Taiyang
      (EX-HN 5), the guoyanre needling technique at Fengchi (GB 20) and xiquedengmei
      needling technique at Cuanzhu (BL 2). The traditional needling technique was used
      at Hegu (LI 4) and Guangming (GB 37). In the control group, traditional even
      needling technique was applied at all the acupoints. The treatment was given once
      every day, continuously for 6 times as one course. There was 1 day at interval.
      After treatment for 4 courses, the changes in visual acuity, diopter and axial
      length were observed before and after treatment. The therapeutic effects were
      evaluated. RESULTS: After treatment, the visual acuity of the naked eyes, and
      diopter were remarkably improved in the patients of the two groups (all P <0.05).
      The improvements in the observation group were better than those in the control
      group (both P <0.05). The axial length did not change in the two groups (both
      P>0.05). The total effective rate was 78.3% (130/166) in the observation group,
      which was better than 57.8% (96/166) in the control group (P <0.05). .
      CONCLUSION: Zheng's stunt needling technique effectively improves the vision,
      rectifies the refractive error and delays the progression of myopia. The
      therapeutic effects of it are better than traditional even needling technique.

PMID- 29473358
TI  - [Guiding-qi acupuncture for dry eye syndrome].
AB  - OBJECTIVE: To observe the clinical efficacy differences between different
      needling methods for dry eye syndrome. METHODS: Sixty patients of dry eye
      syndrome were randomly divided into an observation group and a control group, 30
      cases (60 eyes) in each group. Shangjingming (Extra), Xiajingming (Extra),
      Tongziliao (GB 1), Cuanzhu (BL 2), Fengchi (GB 20), Hegu (LI 4), Sanyinjiao (SP
      6), Taixi (KI 3) and Taichong (LR 3) were selected in the two groups. The control
      group was treated with conventional acupuncture, while the observation group was
      treated with guiding-qi acupuncture. Electroacupuncture (EA) was used at
      bilateral Tongziliao (GB1) and Cuanzhu (BL 2), 30 min per treatment. The
      treatment was given three times per week. Totally 1-month treatment (12
      treatments) was given. The eye symptom score, breakup time of tear film (BUT),
      Schirmer I test (SIT) and visual analogue scale (VAS) score were compared before
      and after treatment in the two groups. The clinical efficacy was compared between
      the two groups. RESULTS: Compared before treatment, the eye symptom score, BUT,
      SIT and VAS score were improved after treatment in the two groups (all P <0.001);
      the improvements of eye symptom score and SIT in the observation group were
      superior to those in the control group (both P<0.05). The differences of BUT and
      VSA score between the two groups were not significant (both P>0.05). The total
      effective rate was 86.7% (52/60) in the observation group, which was superior to
      73.3% (44/60) in the control group (P<0.05). . CONCLUSION: The conventional EA
      and guiding-qi acupuncture combined with EA are both effective for dry eye
      syndrome, and the efficacy of guiding-qi acupuncture combined with EA is superior
      to that of conventional EA.

PMID- 29473359
TI  - [Comparison of the effects of the intervention with electric thermal bian stone
      and air suction cup on blood perfusion at meridian points].
AB  - OBJECTIVE: To observe the impacts of the intervention with electric thermal bian
      stone and air suction cup on blood perfusion (BP) at meridian points and explore
      the approach of accurate measurement and regulation of meridian qi and blood
      balance in "precise acupuncture". METHODS: The laser Doppler line scanner (LDLS)
      was used to measure BP at bilateral yuan-primary points at the pericardium
      meridian, the triple energizer meridian, the gallbladder meridian and the liver
      meridian (small cycle of jueyin to shaoyang meridians) at 31 healthy receptors.
      The bias ratio of blood perfusion (BPBR) deviated to the reference value was
      calculated. The electric thermal bian stone and air suction cup were used in the
      intervention at the he-sea points of the affected meridians in which BPBR was
      relatively higher at the yuan-primary points. The electric thermal bian stone
      therapy was used when BPBR was less than -30% and the air suction cupping therapy
      was used when BPBR was higher than 30%. BP was measured twice before intervention
      and it was measured separately at the moment after intervention and in 20 min
      after intervention. The means of BP before and after intervention and the change
      ratio of blood perfusion (BPCR) before intervention, at the moment after
      intervention and 20 min after intervention were calculated. RESULTS: 1. After the
      intervention of electric thermal bian stone, BP mean was increased from (103.51+/
      41.21) PU to (121.97+/-56.22) PU (P<0.05). Before intervention, at the moment
      after intervention and 20 min after intervention, separately, BRCR were (-0.58+/
      16.18)%, (23.58+/-48.85) % and (25.62+/-65.89) %. BPCR at the moment after
      treatment was increased significantly as compared with that before intervention
      (P<0.01). The difference was not significant in 20 min after intervention and
      before intervention (P>0.05), but the change ratio was highly remained. 2. After
      intervention with air suction cup, BP mean was reduced from (194.83+/-81.14) PU
      to (173.88+/-88.26) PU. Before intervention, at the moment after intervention and
      20 min after intervention, separately, BPCR were (7.62+/-30.49)%, (-12.12+/
      18.20)% and (-14.35+/-21.25)%. BPCR at the moment after intervention and in 20
      min after intervention were significantly different from that before intervention
      (both P<0.01). . CONCLUSION: The electric thermal bian stone increases the blood
      flow at the yuan-primary point when acting on the he-sea point of the same
      meridian. The influence of the air suction cup is opposite.

PMID- 29473360
TI  - [Exploration of the meridian differentiation law in polycystic ovarian syndrome
      of hirsutism based on data mining technology].
AB  - OBJECTIVE: To analyze the distribution characteristics of hirsutism and the law
      of meridian differentiation in polycystic ovarian syndrome (PCOS). METHODS: For
      the patients of PCOS, the modified Ferriman-Gallwey score (mF-G score) was
      adopted to evaluate the hirsutism distribution. The clementine data mining
      software was used to analyze the distribution region of hirsutism and the
      correlation with meridian. RESULTS: A total of 141 patients of PCOS participated
      in the study. The most common regions of hirsutism were in the upper lip (50.35%)
      and the lower abdomen (34.04%). The higher frequencies of hirsutism at two
      regions were at the upper lip and lower abdomen (24.82%), the upper lip and chest
      (12.06%) and the upper lip and thigh (11.35%). In the analysis on the correlation
      of the upper lip, lower abdomen and chest with other regions, hirsutism was more
      common in the nearby regions. In reference to the running course of meridian, the
      frequencies of hirsutism from high to low were the conception vessel (63.12%),
      the thoroughfare vessel (61.70%), the liver meridian of foot-jueyin (58.16%) and
      the stomach meridian of foot-yangming (57.45%). According to Miraculous Pivot:
      Yinyang Twenty-Five Persons, the high incidence of hirsutism (59.57%) resulted
      from the change of qi and blood in yangming meridian. . CONCLUSION: Blood plays
      the important role in the growth of body hair. Regarding the yinyang attribution,
      the incidence of hirsutism at the yin regions is higher than the yang regions.
      The occurrence of hirsutism is closely related to qi and blood changes in
      meridians. The conception vessel, the thoroughfare vessel, the liver meridian of
      foot-jueyin and yangming meridian act highly on the disease.

PMID- 29473361
TI  - [Effects of electroacupuncture on the expression of adenosine receptors in the
      heart tissue of myocardial ischemia rats].
AB  - OBJECTIVE: To explore the impact of electroacupuncture (EA) on the protein
      expression of adenosine receptors in the heart of the rats with myocardial
      ischemia (MI). METHODS: Thirty healthy male SD rats were divided randomly into a
      control group (n=6), a model group (n=12) and an EA group (n=12). We ligated the
      left anterior descending artery (LAD) for MI model in the model group and EA
      group, and exposed the heart after opening the chest without ligation in the
      control group. EA, 2 Hz /15 Hz and 1.5-2 mA, was applied at bilateral"Neiguan"(PC
      6) in the EA group for 20 min, once a day for continuous 5 days. No intervention
      except grabbing and fixation was used in the control group and model group. We
      applied 2% TTC staining to observe the infarct size of myocardium, colorimetry to
      analyze serum lactic dehydrogenase (LDH), creatine kinase (CK), creatine kinase
      isoenzyme (CK-MB), radio-immunity assessment to detect cardiac troponin T (cTnT),
      Western blot to evaluate the adenosine A1 receptor (A1AR), A2aAR, A2bAR and A3AR.
      RESULTS: After treatment, myocardial infarction of (27.56+/-3.24)% was obvious in
      the model group; the myocardial infarction in the EA group was (21.04+/-3.61)%,
      with statistical significance (P<0.05). The expressions of serum LDH, CK, CK-MB
      and cTnT levels in the model group increased compared with those in the control
      group (all P<0.01), and the expressions of LDH, CK, CK-MB and cTnT levels in the
      EA group decreased compared with those in the model group (P<0.05,P<0.01). The
      A1AR expression in the model group was not different from that in the control
      group (P>0.05), and A2aAR,A2bAR,A3AR expressions decreased (P<0.05, P<0.01).
      A2aAR and A2bAR expressions in the EA group increased compared with those in the
      model group (both P<0.01), and there was no statistical significance between A1AR
      and A3AR expressions (both P>0.05). . CONCLUSION: EA may achieve cardioprotective
      effect by regulating the expressions of A2aAR and A2bAR in myocardial tissue,
      which induce the corresponding signal cascade for reducing myocardial infarction
      area.

PMID- 29473362
TI  - [Effects of electroacupuncture on expression of CD36 in peritoneal macrophages of
      rabbits with atherosclerosis].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expressions of
      CD36 gene and protein in peritoneal macrophages of atherosclerotic rabbits, and
      to explore the mechanism of acupuncture regulation of atherosclerosis. METHODS: A
      total of 26 male New Zealand rabbits were randomly divided into a blank group (7
      rabbits) and a model group (19 rabbits). The rabbits in the blank group were fed
      with common feedstuff, and those in the model group were applied with high fat
      diet and arteria carotis communis bullon injury. One rabbit was sacrificed after
      8 weeks to observe the morphological changes of carotid atherosclerotic plaques
      by HE staining to verify model establishment separately in the blank group and
      model group. The model rabbits were randomized into a control group, an EA group
      and a western medication group, 6 rabbits in each one. Common feedstuff was used
      in the blank group and high fat feed in the other groups. No intervention except
      grabbing and fixation as the EA group was in the blank group and control group.
      Rabbits in the EA group were treated with acupuncture at bilateral "Neiguan" (PC
      6), "Zusanli" (ST 36), "Guanyuan" (CV 4), and EA with sparse-dense wave was
      connected at bilateral "Neiguan" (PC 6) and "Zusanli" (ST 36) for 20 min, 4 Hz/20
      Hz and 1 mA. 20 mL suspension of 1mg/kg/d atorvastatin calcium tablets were
      prescribed by intragastric administration in the western medication group for 4
      courses, 6 d as one course with 1 d between two courses, once a day. The
      expression of CD36 protein in peritoneal macrophages was detected by Western
      blot. Reverse transcription (RT) of RNA and polymerase chain reaction (PCR) of
      cDNA were used to detect the expression of CD36 mRNA in peritoneal macrophages.
      RESULTS: In the blank group, the vascular wall thickness was uniform and the
      endothelium was intact. There was no accumulation of foam cells and
      atherosclerotic plaques. In the model group, the intima of the artery obviously
      thickened; the intima was damaged; the atherosclerotic plaque and inflammatory
      cell infiltration were found in the intima, and the foam cells were seen. After
      treatment, the expressions of CD36 protein and CD36 mRNA in the control group, EA
      group and western medication group were higher than those in the blank group (all
      P<0.01). Those in the EA group and western medication group were lower than the
      expressions in the control group (all P<0.01). There was no statistical
      significance for the expressions of CD36 protein and CD36 mRNA between the EA
      group and the western medication group (both P>0.05). . CONCLUSION: EA can reduce
      the expressions of CD36 protein and CD36 mRNA in peritoneal macrophages of
      atherosclerotic rabbits, which may be one of the mechanisms of EA treatment of
      atherosclerosis.

PMID- 29473363
TI  - [Analysis on standardization of patient posture for acupuncture treatment].
AB  - The standardization of patient posture for acupuncture treatment was discussed.
      According to the opinions in Neijing (Inner Canon of Huangdi), combined with the
      clinical practice of acupuncture, it was believed that the patient posture for
      acupuncture treatment should be standardized based on Neijing. The standardized
      patient posture was the foundation of acupuncture, the need of blood flow and
      requirement of acupuncture technique. The combination of three elements was
      beneficial for the traveling of spirit-qi through meridian-acupoint, which could
      regulate balance of yin and yang to treat disease. In addition, the principles
      and methods of standardization of patient posture was proposed, and the important
      clinical significance of standardization of patient posture for acupuncture
      treatment was highlighted.

PMID- 29473364
TI  - [Discussion on several contents of textbook Acupuncture and Moxibustion (New
      Century 4th Edition)].
AB  - The textbook Acupuncture and Moxibustion (New Century 4th Edition) was published
      by China Press of Traditional Chinese Medicine in August of 2016. The author
      proposed several discussions in the textbook. The information, including the
      issue date of China national standard Standardized Manipulations of Acupuncture
      and Moxibustion, the number of foreign countries where China medical teams were
      assigned, and the number of acupuncture indications recommended by WHO, was not
      accurate. The content, including several methods of acupoint location,
      specification of filiform needles, rotating angle of needle, disinfection of
      needles and skin, locations and indications of scalp acupuncture, etc. should be
      corrected. Besides, the writing of textbooks should follow national or industry
      standards.

PMID- 29473365
TI  - [The textual research of "body cun"].
AB  - Although the concept of "body cun" was proposed in Neijing (Inner Canon of
      Huangdi), it was matured in Qianjin Yaofang (Invaluable Prescriptions for Ready
      Reference) in Tang Dynasty, so it was believed by the majority of physicians this
      term was firstly proposed in Qianjin Yaofang. In this study, the literature
      regarding "body cun" was reviewed, and it was believed the term was originated
      from Chongguangbuzheng Huangdineijingsuwen, when WANG bing noted Suwen (The Plain
      Questions). The connotation of the "body cun" included multiple meanings, such as
      bone cun, finger cun and so on, and the points of view were different in
      different periods, different doctors or scholars. From the respective explanation
      of bone cun and finger cun to the combination use in Ming Dynasty and Qing
      Dynasty, the extension of the term was embodied. After the establishment of term'
      s connotation and extension, the translation of the term was accurate and clear.

PMID- 29473366
TI  - [Study on the white channel system carved on the wooden acupoint figurine of
      Laoguanshan: comments on lacquer-coating acupoint figure].
AB  - There are two systems as the red channel system and the white channel system
      carved or painted on the wooden figurine of Laoguanshan of Benque school. The two
      systems are horizontally staggered each other without overlapped. The red channel
      system, similar to Shuangbaoshan wooden figurine, have channels, but without
      points. For the white channel system, the running courses of channels result from
      the sensation distributions of the points after optional stimulation. The
      Laoguanshan wooden figurine focuses on the illustration of the white channel
      system, named as white channel figurine. Compared with the Shuangbaoshan red
      channel figurine, together with examples, such as the running course of the white
      channel related to the meridian of heart-transfer-point, the white channel
      related to the belt vessel linking to lung-transfer-point, stomach-transfer-point
      and kidney-transfer-point, as well as the corresponding photographs. It is
      indicated that the Laoguanshan white channel figurine is a training aid for
      testing the sensation marching along channel (SMC) caused by transfer-point
      stimulation. The white channel system is a flexible way of channel. The study
      aims to observe the QI/SMC reaching the affected area and contributes to clinical
      practice. This discovery is not related to the "intermediate link theory" in the
      Yellow Emperor meridian system.

PMID- 29473367
TI  - [The relationship between acupuncture-moxibustion theory of DOU Hanqing and Neo-
      Confucianism].
AB  - For the construction factors of acupuncture-moxibustion theory of DOU Hanqing, a
      doctor in Jin-Yuan Dynasty, we studied his life, acupuncture-moxibustion theory
      and culture background in the History of Medicine and Philosophy of Science &
      Technology. It was found that the major source of DOU Hanqing' s Confucianism was
      the CHENG-ZHU Neo-Confucianism. The data show that Neo-Confucianism played an
      important role in the enrichment of his human nature, spirit, moral cultivation
      and political talent, making him a scholar in the Jin-Yuan dynasty, also shaping
      his medical ethics, medical skill and acupuncture-moxibustion theory. The
      inheritance, development and application of CHENG-ZHU Neo-Confucianism provided
      the most fundamental thinking, research methods and patterns for DOU Hanqing to
      interpret the acupuncture classics, summarize his teachers' experience and
      develop his theoretical system. DOU Hanqing' s acupuncture-moxibustion practice
      and theory reached a new level, because he took acupuncture-moxibustion as one of
      the knowledge investigation and attainment of CHENG-ZHU Neo-Confucianism.

PMID- 29473368
TI  - [Version and compilation of Harikyuuhousouyou of Vietnamese medical book].
AB  - Harikyuuhousouyou (<<>>)was written in 1827 and the author is unknown. The book
      has only one version which is collected by the National Library of Vietnam. The
      book contains one volume and includes contraindication of acupuncture and
      moxibustion, meridian points, point locations, indications and the therapeutic
      methods at extraordinary points. They are mainly cited from Zhen Jiu Da Quan
      (<<>>Great Compendium on Acupuncture and Moxibustion) by XU Feng, Yi Xue Ru Men
      (<<>>Elementary Medicine) by LI Chan and Shou Shi Bao Yuan (<<>> Longevity and
      Health Preservation) by GONG Tingxian in the Ming Dynasty. In the paper, in view
      of the characteristics of version and compilation, the hand-coped book was
      introduced. It was explored that Vietnam acupuncture absorbed Chinese medicine
      and emphasized clinical practice rather than theoretic statement.

PMID- 29473369
TI  - [Clinical data analysis of 2491 acupuncture inpatient consultations: a report
      from Qilu Hospital of Shandong University].
AB  - OBJECTIVE: To summarize the 2491 acupuncture inpatient consultations in Qilu
      Hospital of Shandong University during 2014, and analyze the application of
      acupuncture in comprehensive hospital, hoping to provide direction and methods
      for clinical practice and scientific research of acupuncture. METHODS: The
      consultation record and hospitalization information during 2014 in Department of
      Acupuncture-Moxibustion and Tuina, Qilu Hospital of Shandong University, were
      collected and summarized through Inpatient Information Management System. The
      distribution of consultation discipline and disease were analyzed. RESULTS: Among
      all the consultations, 15 second-class disciplines were involved, and the number
      of neurology and surgery was 1399, accounting for 59.00% of all consultation. 111
      types of diseases were found in consultation, mainly postoperative complications,
      cerebrovascular disease and arthropathy. The primary disease of consultations
      involved all the systems, mainly nervous system disease, musculoskeletal system
      disease, connective tissue diseases and genitourinary system diseases, accounting
      for 73.89% of all consultations. . CONCLUSION: Acupuncture is closely related
      with clinical disciplines of neurology and surgery. The cooperation between
      acupuncture and pediatrics and oncology should be strengthened. Acupuncture has
      an advantage over treating postoperative complications and neuromuscular
      diseases.

PMID- 29473370
TI  - [The design and application of a moxibustion instrument with less harmful smoke
      and direction adjustment].
AB  - The design of a clip-on moxibustion instrument which could adjust the directions
      and absorb harmful granules of moxa smoke was introduced in this paper. It was
      designed to solve the problems in home health care and clinical treatment, such
      as the inconvenience of adjustment of moxibustion directions and temperature,
      more dust and granules of moxa smoke and inconvenience of moxibustion placement.
      The main part of moxibustion instrument was made up of moxibustion box, bracket
      and base clamp. The moxibustion box could fix moxa stick and absorb smoke
      granules; the bracket could be twisted to adjust the direction of moxibustion
      box; the base clamp was aimed to fix moxibustion box on the edge of the object to
      save space. This moxibustion instrument could be used for various indications of
      moxibustion, especially in the joints or body parts with less muscles; and it can
      significantly enhance the pertinence and safety of moxibustion, and reduce the
      labor intensity. This moxibustion instrument is original and unique, simple and
      reasonable, easy to operate, with low cost and good effect, which will increase
      new vitality for the popularization and development of moxibustion.

PMID- 29473371
TI  - [Research progress of fire needling for chronic gastritis].
AB  - To explore the efficacy and mechanism of fire needling for chronic gastritis,
      "fire needling" and "chronic gastritis" were selected as keywords to collect
      literature in PubMed, CNKI database and WanFang database. The clinical and
      experiment literature regarding fire needling for chronic gastritis was analyzed
      to make a comprehensive discussion on the efficacy and action mechanism of fire
      needling for chronic gastritis. The results indicated the efficacy of fire
      needling for chronic gastritis was superior to that of medication or filiform
      needle. The combination of fire needling and medication, acupoint injection and
      filiform needle could further improve the therapeutic effect for chronic
      gastritis. From the perspectives of TCM and western medicine, the action
      mechanism of fire needling for chronic gastritis was explored, and it was
      believed the fire-needle therapy has the effects of removing and nourishing,
      which conformed to the clinical syndromes of chronic gastritis. The fire needle
      could affect the prognosis by regulating the central nerve system, improving
      local blood circulation, regulating immune inflammation and regulating
      gastrointestinal hormones.

PMID- 29473372
TI  - Risk factors for benign prostatic enlargement: The role of lifestyle habits at
      younger age. The #Controllati2017 initiative study group.
AB  - OBJECTIVE: The risk factors for benign prostatic enlargement (BPE) are not well
      understood and particularly few data are available from Italian population.
      MATERIALS AND METHODS: This was an observational cross sectional study aimed to
      examine the association between several risk factors and BPE. During the
      "#Controllati2017" initiative, men aged 18 years or more were invited to attend
      participating urologic centers for a free of charge visit for counseling about
      urologic or andrologic conditions. Each participating man underwent a physical
      examination including digital rectal examination (DRE). Further he was asked
      about his medical history, urologic symptoms, sexual activity and related
      problems. Diagnosis of BPE was made by the urologist after DRE. RESULTS: Out of
      the 1902 [mean age 54 years (SD 12, range 18-92)] considered men, a total of 603
      subjects (31.7%) had diagnosis of BPE. The diagnosis of BPE increased from 9.3%
      in men aged < = 50 years, to 34.1% in those aged 51-60 years and to 58.7% among
      men aged > 60 years. A history of hypertension, diabetes, heart diseases,
      hypercholesterolemia and hypertriglyceridemia were all significantly associated
      with an increased risk of BPE in the total series and, although not always in a
      statistically significant way, in strata of age. Physical activity (PA) was
      significantly associated with a decreased risk of BPE. We have further analyzed
      the risk of BPE in men with one or more of the identified risk factors (i.e.
      hypertension, diabetes, heart disease, hypercholesterolemia, hypertriglyceridemia
      and low PA): the risk of BPE increased with number of risk factors reported by
      the subjects. The estimated risk were higher among younger men. CONCLUSION: In
      our study a history of hypertension, diabetes, heart disease,
      hypercholesterolemia and hypertriglyceridemia increased the risk and physical
      activity lowered the risk of BPE. This risk profile was observed also in men aged
      < 50 years.

PMID- 29473373
TI  - Medical management in locally advanced and metastatic prostate cancer: Does
      changes in treatment policy have any specific effect on PSA levels?
AB  - OBJECTIVE: Androgen deprivation therapy (ADT) is commonly used as a first-line
      treatment for locally advanced and metastatic prostatic cancer (Pca). There is no
      consensus about which alternative treatment should be used after the failure of
      initial ADT. We aimed to investigate the effect of changes in treatment on PSA
      and testosterone levels. MATERIAL AND METHODS: A total of 120 patients with an
      established diagnosis of either locally advanced or metastatic Pca in two
      different centers. Depending on the type of medical and/or surgical management
      protocol planned at initial presentation, all cases were divided into three main
      groups as follows. Group 1 (n: 80) included the patients who underwent medical
      management during whole follow-up period in whom the initial management protocol
      was later on switched to another medical treatment with different agents, Group 2
      (n: 20) included patients who were initially treated with a medical management
      protocol and switched to surgical castration during follow-up evaluation and
      lastly Group 3 (n: 20) included the patients undergoing treated surgical
      castration as initial treatment modality without any further medical management
      protocol. RESULTS: Evaluation of our data did clearly demonstrate a statistically
      significant difference between the initial and final PSA as well as testosterone
      levels in Group 1 cases. Mean PSA and testosterone levels increased significantly
      in these cases despite a change in hormonal therapy by using another agent for
      androgen deprivation. Cases in Group 2 and 3 cases did not show any statistically
      significant difference with respect to the mean PSA as well as testosterone
      values during the same follow-up period. CONCLUSIONS: Our data clearly indicated
      that in case of a biochemical progression, switching into another alternative
      medical treatment was not effective enough in limiting the rising PSA levels in a
      statistically significant manner when compared with the approaches of switching
      to surgical castration after initial medical treatment or continuing with regular
      and close follow-up after initial surgical castration alone.

PMID- 29473374
TI  - The association between prostatitis and prostate cancer. Systematic review and
      meta-analysis.
AB  - OBJECTIVE: The main outcome of this review was the association between a history
      of clinical chronic prostatitis (NIH category II or III) and a histologically
      confirmed diagnosis of prostate cancer. MATERIALS AND METHODS: Crude odds ratios
      and 95% confidence intervals (CI) were calculated to analyze dichotomous data.
      For analysis of pooled data we adopted a random-effects model and the inverse
      variance weighing method. Heterogeneity was assessed by calculating the I2 value.
      RESULTS: Out of 2794 screened records, we retrieved 16 full-text articles written
      in English, reporting the data of 15 case-control studies, involving 422.943
      patients. Pooled analysis resulted in a significant crude odds ratio of 1.83 (95%
      CI: 1.43 to 2.35; P < 0.00001). The total set of data showed considerable
      heterogeneity (I2 = 91%). Both the Egger's test and the Begg's test for funnel
      plot asymmetry did not reach statistical significance. The 'trim and fill' method
      applied to the funnel plot imputed 3 missing studies and the resulting adjusted
      estimate of the odds ratio was 2.12 (95% CI: 1.38 to 3.22). According to GRADE
      criteria, the overall quality of the meta-analysis data is low, mainly due to the
      presence of bias, confounders and extreme effect size outliers. Five among the
      included studies reported data assessed in 8015 African-American subjects. Pooled
      analysis resulted in a non-significant crude odds ratio of 1.59 (95% CI: 0.71 to
      3.57; P = 0.26), and considerable heterogeneity (I2 = 90%). CONCLUSIONS: Meta
      analysis of 15 case-control studies shows that a history of clinical chronic
      prostatitis can significantly increase the odds for prostate cancer in the
      general population, whereas such association in African-American individuals
      remains uncertain.

PMID- 29473375
TI  - Evaluation of the complications in laparoscopic retroperitoneal radical
      nephrectomy; An experience of high volume centre.
AB  - OBJECTIVES: To provide a standardised report of complications after
      retroperitoneal laparoscopic radical nephrectomy (rLRN) in a high-volume centre
      using Clavien-Dindo classification. MATERIALS AND METHODS: We analysed records
      maintained in a prospective database of 330 consecutive patients that underwent
      rLRN between March 1995 and September 2016. All complications were graded
      according to the modified Clavien-Dindo classification. Three generations of
      surgeons were defined and the learning curve in rLRN was evaluated by comparing
      the first 100 cases (Group A) performed by firstgeneration surgeons with the last
      100 cases (Group B) by thirdgeneration surgeons. RESULTS: The mean age of our
      cohort was 66 +/- 11.9 years. The overall complication rate was 19.7%. The
      majority of complications (12.7%) were Clavien 1 (5.1%) and Clavien 2 (7.6%) and
      did not require any interventions; blood transfusion was the most frequently
      encountered intervention (4.8%). Half of which were because of major
      intraoperative bleeding. Mortality rate was 0.9%. We found a trend towards lower
      complication rate in group B (19%) compared to group A (23%); this was mainly
      because of the reduction in the incidence of Clavien 1 and 2 complications. The
      pathological stage varied significantly in the two groups while the rate of
      negative surgical margins was comparable. CONCLUSIONS: rLRN is a safe procedure
      with an acceptable rate of complications. The learning curve was shorter for the
      thirdgeneration surgeons (group B); although these surgeons operated on a
      significantly higher number of patients with more advanced diseases. The Clavien
      Dindo classification is suitable for assessing rLRN complications. Adopting this
      standardised system can help in the evaluation and comparison of surgical quality
      of LRN series.

PMID- 29473376
TI  - Can re-cTURBT be useful in pT1HG disease as a risk indicator of recurrence and
      progression? A single centre experience.
AB  - INTRODUCTION: Understaging after initial transurethral resection is common in
      patients with high-risk non muscle infiltrating bladder cancer (NMIBC) and can
      delay accurate diagnosis and definitive treatment. The rate of upstaging from T1
      to T2 disease after repeated transurethral resection ranges from 0 to 28%,
      although the rate of upstaging may be even higher up to 49% when muscularis
      propria is absent in the first specimen. A restaging classic transurethral
      resection of bladder tumour (re-cTURBT) is the better predictor of early stage
      progression. According to some reports, the rate of positivity for tumor in re
      cTURBT performed within eight weeks after initial cTURBT was as high as 18-77%,
      and in about 40% of the patients a change in tumor stage was reported. We aimed
      to investigate, in high risk group, the presence of residual tumor following
      white light classical transurethral resection of bladder tumor (WLre-cTURBT) and
      the different recurrence and progression rate between patients with persistent or
      negative (pT0) oncological disease after WLre-cTURBT. MATERIALS AND METHODS: A
      cohort of 285 patients presenting with primitive bladder cancer underwent to
      WLcTURBT from January 2011 to December 2015; out of them 92 (32.28%) were T1HG.
      In according to EAU guidelines 2011, after 4-6 weeks all HG bladder cancer
      patients underwent a WL recTURBT . All patients were submitted to a subsequent
      followup including cystoscopy every 3 months with multiple biopsies, randomly and
      in the previous zone of resection; urinary citology on 3 specimens and
      kidney/bladder ultrasound every 6 months. The average follow-up was 48 months.
      RESULTS: Following WLre-cTURBT we observed a persistent disease in 18 (15.2%)
      patients: 14 (77.7%) with a HG-NMIBC and 4 (22.2%) with a high grade (HG) muscle
      invasive bladder cancer (pT2HG). After follow up of all 92 patients according to
      the guidelines EAU, we observed recurrence in 36/92 (39.1%) and progression in
      14/92 (15.2%). Of 14 NMIBC with persistent disease, 10 patients (71.4%) showed
      recurrence: 4 patients (40%) were pT1HG with concomitant carcinoma in situ (CIS),
      3 patients (30%) multifocal pTaHG, 2 (20%) patients CIS and one patient (10%) a
      muscle invasive neoplasm (pT2HG). Instead of the group of 48 patients pT0
      following WL recTURBT, we observed recurrence in 26 patients (54.1%) and in two
      patients (4.1%) progressions, who presented after 3 months in association with
      CIS. The remaining 22 patients (45.9%) with initial pT1HG are still progression
      free. Multivariate analysis showed that the most important variable of early
      progression were persistent neoplasm and histopathological findings at WLre
      cTURBt (p = 0.01), followed by the Summary No conflict of interest declared.
      INTRODUCTION Bladder cancer is a common genito-urinary malignancy, with
      transitional cell carcinoma comprising nearly 90% of all primary bladder tumours.
      At the first diagnosis 70% to 80% of urothelial tumours are confined to the
      epithelium, the remainder is characterized by muscle invasion. A significant
      number of patients with high risk non-muscle invasive bladder tumours (HG-NMIBT)
      treated with white light classic transurethral resection of bladder tumours
      (WLcTURBT) and intravesical BCG will progress to invasive disease (1-3).
      Progression to muscle invasion (pT2) mandates immediate radical cystectomy (4).
      WLcTURBT is the standard initial therapy for NMIBT, but the high percentage of
      recurrence after surgery is still an unresolved problem (5). High grade pT1
      bladder neoplasm (pT1HG) really represents a therapeutic challenge due to the
      high risk of progression (about 15-30%) to muscle-invasive disease, usually
      within 5 years (6). However, no consensus exists regarding the treatment of
      patients with recurrent bladder tumours that invade the lamina propria (pT1) (7
      9). Recent studies suggested that the first cTURBT may be incomplete in a
      significant number of cases (10). Understaging at the time of the initial
      transurethral resection is common for patients with high-risk NMIBC and can delay
      accurate diagnosis and definitive treatment. It is therefore recommended for
      patients with high-risk disease and in those with large or multiple tumors or
      when the initial transurethral resection is incomplete, to repeat WLre-cTURBT
      within 2-6 DOI: 10.4081/aiua.2017.4.272 result of the first cystoscopy (p =
      0.002) and presence of CIS (p = 0.02). DISCUSSION: Following WLre-cTURBt in HG
      NMIBC patients we identified in 15% of cases a persistent disease with a 4.3% of
      MIBC. In the high risk persistent bladder neoplasms group we observed recurrent
      and progression rate higher than in T0 bladder tumours group (Delta = + 17.3% and
      = Delta + 62.5%, p < 0.05.

PMID- 29473377
TI  - The correlation between biological activity and diffusion-weighted MR imaging and
      ADC value in cases with prostate cancer.
AB  - PURPOSE: Firstly, we aimed to investigate the correlation among dynamic
      contrasted magnetic resonance (MR) images, diffusion-weighted MR images, and
      apparent diffusion coefficent (ADC) values in patients with prostate cancer.
      Secondly, we aimed to investigate the roles of these variables on clinical risk
      classification and the biological behavior of the prostate cancer. METHODS: A
      total of sixty with prostatic adenocarcinoma patients diagnosed between January
      2011 and May 2013 were retrospectively included in the study. Risk classification
      of patients were evaluated as low-risk (Group 1) (n = 20) (Stage T1c-T2a, PSA <
      10 ng/ml, Gleason Score < 7), moderate-risk (Group 2) (n = 18) (Stage T1b-T2c,
      PSA = 10-20 ng/ml, Gleason Score = 7) and high-risk (Group 3) (n = 22) (Stage >
      T3a, PSA > 20 ng/ml, Gleason Score > 7). Diffusion-weighted MR images, dynamic
      contrasted MR images, and ADC values of the prostates were correlated. RESULTS:
      ADC values of the cases in Group 3 were lower than those of the other groups (p <
      0.001). ADC values of the areas without malignancy did not differ significantly
      between groups (p > 0.05). Biological activity of the tumor tissue was determined
      by GS, while a negative correlation was observed between GSs and ADC values of
      the patients, (p < 0.001). CONCLUSION: In tumors with higher Gleason scores,
      lower ADC values were obtained. These measured values can play a role in the
      noninvasive determination of the cellularity of the tumoral mass.

PMID- 29473378
TI  - Ureteroscopy in pregnant women with complicated colic pain: Is there any risk of
      premature labor?
AB  - OBJECTIVE: Clinical presentation of ureteral stones during pregnancy is generally
      with renal colic pain. The aim of this study is to present our experience in the
      management of renal colic during pregnancy in emergency settings. MATERIALS AND
      METHODS: 208 pregnant patients who presented to emergency department with renal
      colic pain and underwent ureteroscopy (URS) due to failed conservative therapy
      were enrolled in the study. Urinary tract stones were diagnosed either with
      ultrasound (US) examination or during URS. Laser lithotripsy and double J (DJ)
      stent placement were routinely done in all patients with ureteral stones. The
      incidence of infective complications and premature uterine contractions (PUC) due
      to URS were compared. RESULTS: No stone was identified in 36.1% (n = 75) of
      patients with using US and diagnostic URS. Of the remaining 133 patients, 30
      (22.6%) had no stone at US but stones were diagnosed during diagnostic URS. The
      type of anesthesia had no significant effect on PUC. An increased risk of sepsis
      and PUC was found in patients with fever at the initial presentation.
      Interestingly, PUC was more frequent in patients with lower serum magnesium
      levels. There was a significant correlation with time delay until the
      intervention and the risk of urosepsis and PUC, individually. CONCLUSIONS:
      Ureteroscopy is a safe option for evaluation of pregnant patients with unresolved
      renal colic. According to the current findings, timing of the operation is the
      most important factor affecting the septic risks and abortion threat. Surgical
      intervention with URS must be planned as soon as possible.

PMID- 29473379
TI  - A rare cause of acute post renal failure: Retroperitoneal fibrosis.
AB  - Retroperitoneal fibrosis is an inflammatory process which may cause acute renal
      failure. In patients who admitted to emergency services with obstructive
      uropathy, retroperitoneal fibrosis should be considered in the differential
      diagnosis. We present our ten cases who admitted to emergency department with
      obstructive acute renal failure related to retroperitoneal fibrosis.

PMID- 29473380
TI  - Longitudinal prospective observational type study about determinants of renal
      resistive index variations in chronic renal failure patients treated with
      conventional medical and dietetic therapy.
AB  - OBJECTIVE: This longitudinal prospective observational type study was conceived
      with the aim to examine the impact on renal resistive index (RRI) of the
      variables that we can manipulate with therapeutic and or dietetic interventions
      in a chronic kidney disease population in order to known which of these variables
      was statistically related to changes in RRI and therefore could become the object
      of the greatest therapeutic effort. MATERIAL AND METHODS: This study was
      undertaken between May 2016 to May 2017 in the outpatient nephrology and urology
      clinic of San Donato Hospital in Arezzo. The study population (84 patients: 47
      males and 37 females) was randomly selected among the chronic kidney patients
      (with various degrees of renal impairment) affected by hypertension and or
      diabetes mellitus. After a comprehensive medical examination these patients were
      submitted to determination of serum creatinine, glycated hemoglobin, 24-hour
      urinary albumin excretion and finally renal Doppler ultrasonography. Then the
      patients were submitted to a full therapeutic and dietetic intervention to
      ameliorate the renal impairment by a wide range of actions and after on average a
      one-year interval were submitted again to a new medical examination and a second
      determination of serum creatinine, glycated hemoglobin, 24-hour urinary albumin
      excretion and a new renal Doppler ultrasonography too. RESULTS: The comparison
      between basal and final data revealed a slight reduction in the mean of bilateral
      renal resistance indices (Delta RRI: -0.0182 +/- 0.08), associated to a slight
      increase in the mean glomerular filtration rate (Delta GFR: 0.8738 +/- 10.95
      ml/min/1.73 m2), a reduction in mean body weight (Delta weight: -1.9548 +/- 5.26
      Kg) and mean BMI (Delta BMI: -0.7643 +/- 2.10 Kg/m2) as well as a reduction in
      the mean systolic blood pressure (Delta systolic blood pressure: -8.8333 +/-
      25.19 mmHg). Statistical analysis showed statistically significant correlations
      (p < 0.05) between Delta RRI and Delta weight (p < 0.03), Delta BMI (p < 0.02)
      and Delta systolic blood pressure (p < 0.05). CONCLUSION: Despite the many
      limitations the our study clearly identifies the targets (yet widely known) to
      act on to prevent kidney alterations related to RRI and provides further
      evidence, if any, of the utility of RRI as a key parameter in monitoring patients
      with chronic renal failure and as a valuable tool to drive the clinical efforts
      to contrast the kidney disease.

PMID- 29473381
TI  - Effectiveness on mild stress and mixed urinary incontinence and impact on Quality
      of Life of a phytotherapic product containing astragalus, thyme, lavender, hop,
      equisetum, red clover, cypress and agrimonia at titrated concentrations. Results
      from a monocentric study.
AB  - OBJECTIVES: To assess any beneficial effect on quality of life of a daily
      treatment with a phytotherapic product containing astragalus, thyme, lavender,
      hop, equisetum, red clover, cypress and agrimonia at titrated concentrations in a
      cohort of female patients complaining mild stress urinary incontinence (SUI) or
      mixed urinary incontinence (MUI). MATERIALS AND METHODS: 42 non-consecutive
      female out-patients with mild SUI or mild MUI were assessed with a clinical
      evaluation, International Consultation on Incontinence Questionnaire Short Form
      (ICIQ-SF) and Patients' Perception of Intensity of Urgency Scale (PPIUS) at
      baseline the start of the study and after two months of therapy with the
      phytotherapic product. At the end of the therapy the patients also compiled
      Patient Global Impression of Improvement (PGI-I). RESULTS: After the completion
      of the study there was a trend towards better results in each item of ICIQ-SF,
      but without any statistical significance with an average score in ICIQ-SF-1 of
      3.12 +/- 0.981 versus 3.21 +/- 0.914 (p = 0.556), in ICIQ-SF-2 of 3.69 +/- 1.422
      versus 3.79 +/- 1.372 (p = 0.68) and in ICIQ-SF-3 of 5.95 +/- 1.618 versus 6.14
      +/- 1.670 (p = 0.462). The average reduction of PPIUS was of 0.09 (1.26 +/- 1.481
      versus 1.357 +/- 1.509, p = 0.705). There was a reduction of average consumption
      of pads/die from 1.69 +/- 0.636 to 1.54 +/- 0.543 (p = 0.101). In relation to the
      PGI score, 23/42 patients (54.7%) reported no changes after the completion of the
      therapy, 13/42 (30.9%) reported a slight improvement, 5/42 (11.9%) were much
      improved and 1/42 (2.3%) was slightly worsened. Only 2/42 (4.7%) patients
      discontinued the treatment before of the completion of the study. We did not
      observe any adverse effects during the period of the study. CONCLUSIONS: The
      phytotherapic product seems to cause a slight improvement of the symptoms in a
      good rate of patients. Moreover it has a low rate of withdrawal, due to the lack
      of adverse events.

PMID- 29473382
TI  - A randomized, multicenter, controlled study, comparing efficacy and safety of a
      new complementary and alternative medicine (CAM) versus Solifenacin Succinate in
      women with overactive bladder syndrome.
AB  - INTRODUCTION: To assess efficacy and tolerability of a new complementary and
      alternative medicine (CAM) consisting of vitamins (C and D), herbal products
      (cucurbita maxima, capsicum annum, polygonum capsicatum) and amino acid L
      Glutammina, in the treatment of female Overactive Bladder syndrome (OAB).
      MATERIALS AND METHODS: 90 consecutive women with OAB symptoms were enrolled in
      this prospective, randomized, controlled study. Women were divided randomly into
      two groups of 45 patients each. In group A, women received Solifenacin Succinate
      (SS), 5 mg. once a day for 12 weeks. In group B, women received CAM, 930 mg,
      twice daily for 12 weeks. Women were assessed with 3-day micturition diary,
      Patient Perception of Intensity of Urgency Scale (PPIUS), Overactive Bladder
      questionnaire Short Form (OAB-q SF) and Patient Global Impression of Improvement
      questionnaire (PGI-I). RESULTS: 8 patients in group A and 1 patient in group B
      dropped out from therapy because of side effects. A reduction in the number of
      daily micturitions, nocturia and episodes of urge incontinence was present with
      both SS and CAM with statistically highly significant differences, but CAM was
      significantly more effective than SS. PPIUS and OAB-q SF showed improvements with
      both SS and CAM with a more significant efficacy of CAM. PGI-I, demonstrated
      improvements in the two groups of patients with a greater satisfaction expressed
      by patients treated with CAM. CONCLUSIONS: the small number of patients does not
      permit definitive conclusions; however, the results of the research showed the
      greater effectiveness and tolerability of CAM.

PMID- 29473383
TI  - Prevalence of phimosis and foreskin sliding abnormalities in male adolescents and
      their correlation with later onset of first sexual intercourse.
AB  - INTRODUCTION AND OBJECTIVES: The aim of the study is to evaluate the prevalence
      of andrological abnormalities, such as phimosis and foreskin sliding
      abnormalities among male adolescents, and if these might interfere with
      sexuality, leading to a later onset of sexual experiences. MATERIAL AND METHODS:
      Between April and May 2015 a prevention campaign in andrology was conducted in an
      area surrounding Rome, Ostia and the Ladispoli area, among 15-19 year-old
      students. The screening consisted of a frontal lesson with the students in order
      to explain and raise the awareness of the most common andrological abnormalities
      and diseases. Among the routine anamnestic questions, three additional questions
      were submitted to 18-year-old boys: "Have you ever had sexual intercourse?", "How
      old were you when you had your first sexual intercourse?" and "Have you consulted
      a health professional about your genitals?" Finally a detailed clinical
      examination was performed and the outcome sent to the family and to the General
      Practitioner (GP). RESULTS: A total of 552 high school students were evaluated.
      Out of them 131 (23.7%) were at least 18 years old. Among these, 79 (60.3%) said
      that they had already had full sexual intercourse. The phimosis and foreskin
      sliding abnormalities had a prevalence of 12.9% within the 18-year-old students,
      with a significant prevalence among those who hadn't had any sexual intercourse
      at all, 21.1% vs 7.5% p = 0.023. The age of the complete first sexual experience
      in the circumcised young men was the same as those without phimosis; 89% of the
      boys with phimosis hadn't had an andrological examination in the previous years.
      CONCLUSIONS: Male adolescents with phimosis or preputial sliding abnormalities
      tend to have a late onset of sexual experiences compared to same aged boys
      without phimosis. These data support the urgent need of an andrological
      consultation for all boys at the beginning of, and during, their adolescent
      period because genital abnormalities may interfere with sexuality. Finally, in
      order not to confuse effects with causes, we suggest matching a routine genital
      physical examination in all studies dealing with sexual psychological aspects of
      male adolescents.

PMID- 29473384
TI  - Five-year prospective study on cardiovascular events, in patients with erectile
      dysfunction and hypotestosterone.
AB  - OBJECTIVE: Testosterone levels play a role in cardiac and vascular pathology. In
      the present study we investigated the prognostic significance of this hormone for
      cardiovascular outcome, in a 5-year follow-up. MATERIALS AND METHODS: Our cohort
      included 802 adult subjects, from 40 to 80 years. Patients were excluded if they
      had a past history of peripheral or coronary artery disease, and
      revascularization. A blood sample was drawn to valuate testosterone level, and we
      considered normal testosterone levels 300 ng/dl. FMD (flow mediated dilatation)
      of the brachial artery was assessed by measuring the increase of the brachial
      artery diameter during reactive hyperemia after transient forearm ischemia. B
      mode longitudinal images of the brachial artery were obtained at the level of the
      antecubital fossa. The FMD was defined as the percentage change in the brachial
      artery diameter 60 s after releasing the ischemic cuff. Erectile dysfunction
      (ERD) was assessed by the International Index of Erectile Function-5 (IIEF-5)
      score questionnaire. We considered composite end points including the following
      major adverse cardiovascular events (MACEs) Results: Subjects with lower serum
      testosterone levels (n = 332) had higher prevalence of traditional cardiovascular
      risk factors, such as hypertension (p = 0.009), diabetes (p = 0.03), dyslipidemia
      (p < 0.0001), obesity (p = 0.002), and endothelial function score (p < 0.0001).
      AMI, death after AMI, major stroke and all clinical events were more frequent (p
      < 0.001) in patients with testosterone levels < 300 ng/dl. Further, by multiple
      logistic regression analysis we found that only dyslipidemia (p = 0,001), obesity
      (p = 0,007), testosterone < 300 ng/dl (p < 0,0001) and ED (p < 0,0001) were
      independent predictors of future events. CONCLUSIONS: A therapeutic intervention
      on testosterone may not only have a positive effect on the cardiovascular system
      but also an important role in preventing new cardiovascular events.

PMID- 29473385
TI  - Partial nephrectomy in horseshoe kidney: Primary carcinoid tumor.
AB  - Primary neuroendocrine carcinoma of the kidney is a rarely observed clinical
      condition because neuroendocrine cells are not found in kidney parenchyma. It's
      not clinically and radiologically possible to distinguish from other kidney
      tumors. Incidence with horseshoe kidney anomaly, it should be considered as a
      definitive diagnosis for the patients with this condition. In this case report,
      we reported about a carcinoid tumor in horseshoe kidney in a 37-year-old woman.

PMID- 29473386
TI  - Incidentally discovered pelvic paraganglioma: A case report.
AB  - Paragangliomas (PGL) are rare neuroendocrine tumors of the autonomic nervous
      system originating from paraganglia. Although PGL may arise at any site where
      physiologic paraganglionic tissue exists, the localization in the small pelvis is
      extremely rare. PGL may be hormonally active and release surplus catecholamines
      into the blood or inactive. The asymptomatic cases pose a diagnostic dilemma. We
      describe the case of an asymptomatic PGL arising in the small pelvis sidewall
      presenting as an incidentally discovered asymptomatic mass in a male subject.

PMID- 29473387
TI  - Elderly patient with atypical leiomyoma of the bladder presenting as flank pain:
      A case report.
AB  - Atypical leiomyoma is a rare tumor of the bladder whose correct diagnosis with
      imaging techniques and cystoscopy is difficult. This tumor is prevalent in
      females and more common in middle age. In the present study we report a rare case
      of atypical leiomyoma presenting as flank pain and history of recurrent urinary
      tract infections in an elderly female. Ultrasound (US) showed that the wall of
      bladder was thickening and irregular, especially in the lower part of the
      bladder. US revealed hypoechoic solid mass with dimensions of 37 x 26 mm in the
      posterior bladder wall protruding into the bladder. Computed Tomography scan of
      the patient showed a mass with dimensions of 29 x 38 mm in the posterior wall of
      the bladder that infiltrated the mesenteric fat and also seemed to be invading
      the intestinal wall. According to the general condition and age of our patient,
      we removed all of the mass under spinal anesthesia by transurethral bladder
      resection (TURBT). Biopsy results showed atypical leiomyoma. About 6 months after
      the patient follow-up, no recurrence was observed and symptoms had completely
      resolved. According to the non-specificity of the imaging, of the age of
      presentation and of clinical manifestations of atypical leiomyoma differential
      diagnosis for bladder cancer it is recommended. Only with histopathologic
      findings, the diagnosis can be confirmed.

PMID- 29473388
TI  - Seminal vesicle abscess causing unilateral hydroureteronephrosis: A case report.
AB  - Seminal vesicle abscess (SVA) is a rare urologic entity. It mainly occurs in
      subjects with predisposing factors and may be associated with other urogenital
      infections. We describe the case of a diabetic subject with SVA associated with
      funiculitis, epididymitis and obstructive pyelonephritis. Treatment consisted of
      laparotomic surgical drainage of the abscess and ureteral stent placement.

PMID- 29473389
TI  - Right ectopic intrathoracic kidney: Unusual clinical presentation in a young
      patient affected by scrotal varicocele.
AB  - Intrathoracic kidney is a partial or complete displacement of the kidney above
      the hemidiaphragm into the mediastinal compartment of the thorax. It is usually
      seen as an incidental finding discovered on chest radiograph or abdominal
      ultrasound. However computed tomography consents the correct detection of
      intrathoracic masses and defines their shape, size, and extent. We here report a
      case of ectopic thoracic kidney in a 22-year-old man who had a long history of
      scrotal discomfort associated with right varicocele. Frequently, this ectopia
      does not affect renal function and the stretched ureter provides good drainage.
      In literature, a small number of cases shows that varicocele is a possible mode
      of presentation of kidney tumors, but this is the first case of varicocele
      secondary to intrathoracic kidney ectopia.

PMID- 29473390
TI  - An unusual case of pneumatic nail gun scrotal injury and revision of the
      literature.
AB  - Pneumatic nail guns are hand-held tools commonly utilized in both industrial and
      non occupational setting. These devices facilitate production and boost
      efficiency but also can be a potential cause of serious injuries. Nail guns are
      the most frequent tool associated trauma with hospitalization among construction
      workers. The most common sites of injuries are the hand or fingers followed by
      the lower extremities. We report the first case in literature of a work nail gun
      injury to male external genitalia.

PMID- 29473391
TI  - ?

PMID- 29473392
TI  - [Therapeutic education in pediatric dentistry: analysis of obstacles and levers
      to the development of programmes in France in 2016].
AB  - OBJECTIVE: Over recent years, therapeutic patient education has become part of
      dental medicine. Management of early childhood caries, known to be a very common
      chronic disease, has evolved to include an educational dimension. The objective
      of this study was to identify the levers and barriers to the development of
      formalized therapeutic education programmes and alternatives. METHODS: A
      comprehensive exploratory qualitative study was conducted between November 2015
      and June 2016 on a targeted sample of 15 people aware of the problem of TPE in
      dentistry. RESULTS: The study showed that TPE training in dentistry is
      underdeveloped, despite its numerous benefits: change of the healthcare
      professional's approach, implementation of structured educational programmes,
      development of research, etc. There are many obstacles to the development of TPE
      programmes: insufficient resources, rigid legislation or lack of knowledge of TPE
      practices. The dental profession is an obstacle itself because of its lack of
      understanding and variable degrees of integration the medical community. There
      are multiple levers, but the main ones are changing attitudes of the profession
      and the provision of resources to develop TPE. Although alternatives to TPE
      programmes exist (accompanying measures, short educational strategies, connected
      health), they cannot replace TPE. CONCLUSION: More educational strategies must be
      developed in the field of dentistry. However, the framework of TPE must be
      adapted to the profession to ensure good uptake.

PMID- 29473393
TI  - [Qualitative analysis among electronic cigarette users: practices, use,
      representations].
AB  - INTRODUCTION: Electronic cigarettes are smokeless devices that simulate the act
      of tobacco smoking by spraying an ?e-liquid? and diffusing an aerosol that is
      inhaled by the user. Although the initial enthusiasm observed in 2012-2013 has
      tended to flag, electronic cigarettes are now part of the landscape of smokers
      seeking an alternative to smoking and abstinence. Smoking cessation professionals
      need to meet a growing demand from smokers and must adopt a clear position in
      relation to this device. METHODS: The results presented here were derived from a
      qualitative study conducted with the financial support of the French Directorate
      of Health, part of the Ministry of Social Affairs and Health from September 2014
      to January 2016. RESULTS: The study was based on classical field-work ethnology:
      observations were made during events involving electronic cigarette users and 25
      semi-structured interviews with diverse profiles to clarify a poorly known field.
      This study contributes to the observation and understanding of an emerging
      phenomenon, likely to induce a lasting change in our relationship to tobacco.
      DISCUSSION: The study revealed a wide variety of profiles among smokers
      interested by electronic cigarettes. Men and women, young and old, or former
      smokers, adopt various attitudes when trying this device, and their patterns of
      use often change over the months following initiation.

PMID- 29473394
TI  - [Outbreak of carbon monoxide poisoning in the Ile-de-France region during the
      spring 2016 Seine flooding].
AB  - INTRODUCTION: Heavy rainfall in May 2016 caused large-scale flooding of the Seine
      and its tributaries. Analysis of this unusual event showed that it could recur on
      an even larger scale. The sanitary consequences were less frequently assessed in
      this analysis, particularly the risk of accidental collective carbon monoxide
      (CO) poisoning caused by the use of combustion engine drainage pumps. METHODS: We
      retrospectively reviewed all cases of acute accidental carbon monoxide exposure
      observed in the Ile-de-France region, related to the use of drainage pumps in
      spring and summer 2016 and notified to the Ile-de-France CO poisoning
      surveillance network. RESULTS: Five events were identified, including 45 people
      exposed to carbon monoxide. Thirty-four of these people were poisoned, 5 were not
      poisoned and insufficient data were available for 6 people. Three people showed
      signs of severity and 2 were treated by hyperbaric oxygen therapy. The other
      poisoned individuals were managed in hospital and treated by oxygen therapy. All
      were cured. DISCUSSION: Collective CO poisonings are common sanitary events
      during flooding and can be potentially severe. They can occur during the event or
      over the following days. Preventive measures may help to reduce the risk of CO
      poisoning, such as increased awareness among professionals, better information of
      individuals who rent these types of devices or even the use of CO detectors
      during their use.

PMID- 29473395
TI  - [Health literacy and patient education interventions: a review].
AB  - INTRODUCTION: Low health literacy (HL) is an obstacle to therapeutic patient
      education (TPE), especially for people in a vulnerable situation, who are also at
      greater risk of chronic illnesses and their complications. It therefore seems
      essential to rethink TPE programmes in order to ensure greater equity based on
      analysis of the characteristics of HL interventions and their possible
      relationships with TPE. METHODS: A scoping review of the literature was performed
      from November 2014 to January 2016 using the following search engines:
      MEDLINE/PubMed, EMBASE, PsycINFO, ERIC, OpenGrey, SUDOC, theses.fr and BDSP and
      the following search terms: ?health literacy?, ?Litteratie en sante?, ?literacy?,
      ?Litteratie?, ?numeracy?, ?numeratie?, ?competence en sante? combined with the
      keywords: ?programme?, ?program?, ?intervention?, ?methode?, ?method?,
      ?technique?, ?outil?, ?tool?. RESULTS: After selecting forty out of 206 studies,
      interventions were classified into two main types of specific interventions to
      promote comprehension of resources intended for patients and generally complex
      interventions designed to support and improve HL skills. DISCUSSION: While the
      level of health literacy has an impact on TPE programme accessibility, TPE
      programmes need to be made more accessible and TPE must constitute an opportunity
      to address health literacy needs via its own specific modalities. Creating
      partnerships between social/educational and health settings might be an effective
      strategy to strengthen the interrelationships between HL and TPE, as might
      training that prepares caregivers-educators to improve patient HL. CONCLUSION:
      Interrelationships between HL and TPE are possible. Research should question the
      pedagogical modalities to be used to adapt TPE programs to the HL.

PMID- 29473396
TI  - [Development of a French-language online health policy course: an international
      collaboration].
AB  - OBJECTIVE: To present the process and challenges of developing an online
      competency-based course on public health policy using a collaborative
      international approach. METHODS: Five public health experts, supported by an
      expert in educational technology, adopted a rigorous approach to the development
      of the course: a needs analysis, identification of objectives and competencies,
      development of a pedagogical scenario for each module and target, choice of
      teaching methods and learning activities, material to be identified or developed,
      and the responsibilities and tasks involved. RESULTS: The 2-credit (90-hour)
      graduate course consists of six modules including an integration module. The
      modules start with a variety of case studies: tobacco law (neutral packaging),
      supervised injection sites, housing, integrated services for the frail elderly, a
      prevention programme for mothers from disadvantaged backgrounds, and the
      obligatory use of bicycle helmets. In modules 1, 3, 4 and 5, students learn about
      different stages of the public policy development process: emergence, formulation
      and adoption, implementation and evaluation. Module 2 focuses on the importance
      of values and ideologies in public policy. The integration module allows the
      students to apply the knowledge learned and addresses the role of experts in
      public policy and ethical considerations. CONCLUSION: The course has been
      integrated into the graduate programmes of the participating universities and
      allows students to follow, at a distance, an innovative training programme.

PMID- 29473397
TI  - [Psychiatric readmissions: individual and organizational factors].
AB  - BACKGROUND: Psychiatric readmission often constitutes a criterion to assess the
      effects of various therapies, as well as the impact of organizational changes in
      the healthcare system. It is used to characterize relapse or decompensation. The
      purpose of this study was to determine readmission rates and identify individual
      and organizational factors associated with significant variations in these rates.
      METHODS: Adult psychiatric readmissions were identified from the full-time
      hospital stays registered in psychiatric wards in 2011-2012 in the Nord and Pas
      de-Calais departments of France, available in the medical the RimP psychiatric
      admission database. Readmission rates for various follow-up periods after
      discharge were measured by Kaplan-Meier survival analysis and multivariate
      analysis was conducted using the Cox proportional hazards model. RESULTS:
      Approximately 30,000 adults were hospitalized full-time in psychiatric units of
      the region during the study period. The 24-month readmission rate was 51.6%
      (95%CI: 50.8-52.3%). The Cox model showed that a diagnosis of schizophrenia (F2 -
      HR = 1.72 - 95%CI: 1.61-1.84 - p < 0.001) and personality disorder (F6 - HR =
      1.45 - 95%CI: 1.32-1.58 - p < 0.001) was associated with a higher readmission
      rate. Readmission rates were higher among dependent patients in non-profit
      private hospitals. CONCLUSION: Psychiatric readmission is a very frequent event
      and is linked to organizational as well as individual factors.

PMID- 29473398
TI  - [Factors influencing electronic personal health record (ePHR) adoption by Primary
      Health Care providers in Quebec: Professional and organizational perspective].
AB  - INTRODUCTION: We aimed to describe and analyse the factors and conditions
      influencing ePHR adoption by primary healthcare professionals for the follow-up
      and management of chronic diseases, as perceived by healthcare professionals and
      health organization managers. METHODS: A qualitative study was conducted in the
      context of an ePHR experimentation project in Quebec. In-depth semi-structured
      individual interviews were conducted with 11 professionals and three managers
      directly involved in ePHR implementation in a primary healthcare organization.
      RESULTS: The results highlight the emergence of themes comprising facilitators or
      barriers to ePHR adoption. The main factors identified were the clinicians'
      leadership and previous involvement in organizational transformations, the
      context of practice, technology maturity providing a useful, additional and
      relevant content, integration with the available clinical information systems
      facilitating two-way communication and supporting the development of patient
      professional partnerships and patients' use and adherence. The organizational
      precursors identified refer to the organizational receptivity to change,
      adjustment to participants' values, and the policies and practices set up to
      support ePHR adoption by professionals and their patients. Cost is a major issue
      determining ePHR implementation. CONCLUSION: The factors and conditions
      identified will be useful strategically and operationally to design and implement
      new clinical and organizational practices and develop adapted technologies
      facilitating ePHR adoption by professionals.

PMID- 29473399
TI  - [Palliative care at home: patient care pathways and clinical characteristics].
AB  - INTRODUCTION: The great majority of French people express their desire to receive
      palliative care at home. The objective of this study was to describe the clinical
      care pathways and characteristics of patient receiving hospital at home
      palliative care. METHODS: This study compared the care pathways and clinical
      characteristics of patients receiving palliative care at home in the Ile-de
      France region in 2014. Retrospective data were extracted from the French medical
      information systems programme. RESULTS: 817 patients receiving palliative care at
      home were included in the study. They were older, more often referred to hospital
      at home by a primary care physician, had shorter lengths of stay and more often
      died at home compared to patients without palliative care. Palliative care
      patients mainly presented cancer and received frequent technical nursing care.
      The oldest patients (>= 75 years old) more often presented neurodegenerative
      diseases, were less often transferred to hospital, and more often died at home
      compared to younger patients. A higher proportion of home deaths was observed in
      nursing home residents and patients who died at home required less technical
      nursing care. CONCLUSION: This study provides important information concerning
      admission to hospital at home, the frequent changes of places of care and the
      complexity of maintaining palliative care at home until the patient's death.

PMID- 29473400
TI  - [Stranger isolated minors and the french health care system: qualitative study].
AB  - OBJECTIVE: While waiting for health insurance coverage, unaccompanied foreign
      minors (UFM) can attend PASS healthcare access clinics in French hospitals. The
      aim of this study was to identify UFM's representations and perceptions of the
      French health care system. METHODS: This qualitative study was based on a series
      of individual, semi-structured interviews of UFMs attending a PASS clinic. The
      methodology was approved by the French data protection authority and an ethics
      committee. RESULTS: A total of 21 UFMs were interviewed. Participants expressed
      their satisfaction with health care, although the health care system was
      perceived as a complex system. The prescription is essential, as it enables the
      patient to obtain medications, the ultimate goal of health care access. Not all
      participants knew about the existence of national health insurance. They were
      unable to distinguish between PASS clinics and the hospital in general and the
      screening role of PASS clinics was often poorly understood. The general
      practitioner was not always identified and his role was poorly understood.
      Educators were perceived as playing a decisive role in health care access. Heath
      is essential for all UFMs. None of them referred to mental health issues.
      CONCLUSION: UFMs need better information about the health care system and their
      rights. The educators' health care support training, their knowledge of the
      rights of UFMs and the role of healthcare professionals need to be improved.
      Screening of mental illness needs to be developed.

PMID- 29473401
TI  - [The emergence of patient safety issues in France].
AB  - INTRODUCTION: The objective of this study was to elucidate the conditions of
      emergence of patient safety issues in the public debate and the limits to
      implementation of patient safety in the current health system. METHOD: A
      narrative review of the international literature was conducted by searching
      PubMed, Cairn and Persee databases. RESULTS: The database search retrieved 2,206
      documents, 48 of which were included in the study. The theme of patient safety
      has spread worldwide, but emerged late in France. The delayed emergence of
      patient safety in France is essentially related to the euphemistic approach to
      the problem of patient safety, the difficulty of adopting systematic reasoning,
      the lack of human resources management levers and the ambiguous position of
      patients in relation to patient safety.

PMID- 29473402
TI  - [Health Statistics in Senegal: between political stakes and role playing].
AB  - INTRODUCTION: Many countries have developed disease surveillance systems to deal
      with epidemics, but although health information systems have existed for more
      than two decades, constraints and biases in data collection limit the relevance
      of policy decisions and strategies in the field of health, as priority has been
      given to education and health in developing countries. Donor support has led to
      the development of systems for the production of statistics, designed, among
      other things, to more clearly target interventions in terms of educational
      objectives, action and credibility and enable health systems to continue to
      benefit from external funding. METHODS: We used a classical anthropology approach
      based on observations and in-depth interviews with local and national health
      system actors. RESULTS: The aim of this article is to analyse the real effects of
      the production of health statistics in health care systems and to determine the
      relevance of these figures in the context in which they apply. DISCUSSIONS:
      Health priorities defined by international organizations and technical and
      financial partners focus on diseases considered to be ?priorities? to the
      detriment of neglected diseases, which are perceived as being more important at
      the local level due to their impact on the already limited health systems. We
      describe how health actors within healthcare structures adjust and adapt to
      public health requirements.

PMID- 29473403
TI  - [Job perception and well-being among healthcare workers in Morocco].
AB  - OBJECTIVES: The aim of this study was to evaluate the well-being and occupational
      perception of healthcare workers in Morocco. METHODS: This observational and
      cross-sectional survey, carried out by self-administered questionnaire, was
      conducted in public hospitals in three cities. The target population consisted of
      2,453 healthcare workers, comprising physicians and paramedics with at least two
      years of clinical experience. RESULTS: 1951 healthcare workers returned the
      questionnaire (29.4% physicians and 70.6% allied health personnel).The mean age
      was 40.3 +/- 10.1 years. 79.8% drank tea and 59.6% drank coffee daily to remain
      alert at work. 13.9% were smokers and 5.5% drank alcohol. Medication use
      consisted of analgesics for 28.1% and psychotropic drugs for 11.6%. The
      respective prevalence of general health perception was ?bad or very bad? for
      14.1% to 24.5%. Perceived symptoms varied from 20.4% to 26.2%. Pain and headache
      were the most common symptoms. 53.9% ?often and continuously? experienced stress
      at work. Work requirements were considered to be ?difficult? or ?very difficult?
      by 32.1% to 46.2%.The workplace was unsuitable for 37.2%, salary was inadequate
      for 39.4%, the workload was excessive for 39.8% and the work rate was excessive
      for 43.2%. Relationship with colleagues (work environments and trust) were
      appropriate for 55.6% and 65%, respectively. Relationships with hierarchical
      superiors were appropriate for 15.6% and based on confidence for 13.8%. Perceived
      social support outside of work was high. CONCLUSION: Assessment of well-being and
      occupational risk perception among healthcare workers must be one of the priority
      tasks of occupational health utilities in Moroccan hospitals.

PMID- 29473404
TI  - [Stigma and discrimination experienced by people living with HIV in Togo, in
      2013].
AB  - BACKGROUND: Stigma and discrimination experienced by people living with HIV
      (PLWHA) prevent and delay access to prevention and treatment services. The aim of
      this study was to describe the patterns of stigma and discrimination experienced
      by PLWHA in Togo and to identify the associated factors. METHODS: A cross
      sectional study was conducted in 2013 among PLWHA in Togo in order to collect
      data on stigma or discrimination experiences. Univariate and multivariate
      analyses were performed to identify associated factors. RESULTS: A total of 891
      PLWHA were interviewed, including 848 (95.2%) receiving antiretroviral therapy.
      External stigma (37.9%) was the major form of stigmatization followed by
      internalized stigma (35.4%). The main features of external stigma were gossip
      (36.5%) and issues to access education (36.0%). Internalized stigma mainly
      consisted of a feeling of guilt (37.6%) and self-devaluation (36.0%). In
      univariate and multivariate analysis, female gender was significantly associated
      with stigma (aOR = 1.73, 95% CI [1.08-2.77]). Of the 891 PLWHA, 75 (8.4%)
      reported a violation of their rights. Finally 27 (4.1%) were discouraged from
      having children by a health professional because of their HIV status. CONCLUSION:
      Stigma affects more than one-third of PLWHA in Togo, more particularly females.
      It appears necessary to design new interventions and integrate psychosocial care
      in the management of PLWHA, in addition to antiretroviral therapy.

PMID- 29473405
TI  - [A meta-synthesis on gender, disability and reproductive health in sub-Saharan
      Africa].
AB  - INTRODUCTION: Reproductive health remains a major global health issue. People
      with disabilities face additional discrimination and barriers to access which
      need to be better understood. To contribute to future interventions, we examined
      the intersections between gender and disability related to reproductive health in
      sub-Saharan Africa in the qualitative literature. METHODS: We conducted a meta
      synthesis, using a taxonomic analysis. An inductive and iterative approach was
      adopted to allow exploration of new and emergent semantic variations in themes.
      NVivo 11 Plus was used to code themes. RESULTS: Ten qualitative studies from six
      sub-Saharan African countries were analysed. Two main thematic areas emerged from
      the analysis: 1) gendered roles of people with disabilities are programmed by
      sociocultural normativity, including perceptions about sexuality. They are
      exacerbated by the hegemony of ableism and influenced by the type of reproductive
      health issues experienced by people with disabilities; and 2) experiences of
      disability in interaction with a reproductive health issue are exacerbated by the
      type of disability, influenced by the type of barriers to access, and perceived
      differently depending upon the actors involved. DISCUSSION: The intersections
      between gender and disability embodied by people with disabilities are multiple
      and complex. Not only do imposed gendered roles influence the lives of people
      with disabilities, but their experiences of disability are also intricately
      linked to gender. An intersectional analysis is proposed as a useful support to
      developing future perspectives.

PMID- 29473406
TI  - ?
AB  - Large-scale deployment of new medicines has been observed over the last two
      decades in many Sub-Saharan Africa countries faced with major public health
      issues such as malaria and HIV/AIDS. However, some of these medicines may be
      responsible for varying degrees of toxicity, with adverse drug reactions leading
      to decreased compliance or even discontinuation of treatment. Pharmacovigilance
      systems therefore had to be set up in these countries, such as in Burkina Faso,
      West Africa, which initiated the organization of pharmacovigilance activities in
      2008. Despite this progress, the systems in place have not yet achieved a
      sufficient level of performance to deal with drug-related health issues,
      highlighting the need for further actions. Pharmacovigilance in Burkina Faso can
      be strengthened at multiple levels: pre-service and in-service training of health
      workers; the establishment of active surveillance based on sentinel sites;
      informing the public and raising awareness; and strengthening national
      coordination.

PMID- 29473409
TI  - Self-Powered Temperature-Mapping Sensors Based on Thermo-Magneto-Electric
      Generator.
AB  - We demonstrate a thermo-magneto-electric generator (TMEG) based on second-order
      phase transition of soft magnetic materials that provides a promising pathway for
      scavenging low-grade heat. It takes advantage of the cyclic magnetic forces of
      attraction and repulsion arising through ferromagnetic-to-paramagnetic phase
      transition to create mechanical vibrations that are converted into electricity
      through piezoelectric benders. To enhance the mechanical vibration frequency and
      thereby the output power of the TMEG, we utilize the nonlinear behavior of
      piezoelectric cantilevers and enhanced thermal transport through silver (Ag)
      nanoparticles (NPs) applied on the surface of a soft magnet. This results in
      large enhancement of the oscillation frequency reaching up to 9 Hz (300% higher
      compared with that of the prior literature). Optimization of the piezoelectric
      beam and Ag NP distribution resulted in the realization of nonlinear TMEGs that
      can generate a high output power of 80 MUW across the load resistance of 0.91
      MOmega, which is 2200% higher compared with that of the linear TMEG. Using a
      nonlinear TMEG, we fabricated and evaluated self-powered temperature-mapping
      sensors for monitoring the thermal variations across the surface. Combined, our
      results demonstrate that nonlinear TMEGs can provide additional functionality
      including temperature monitoring, thermal mapping, and powering sensor nodes.

PMID- 29473410
TI  - Determination of Nanoparticle Size Using a Flow Particle-Tracking Method.
AB  - We developed a novel method to determine the mean size of nanoparticles under
      flow conditions, the flow particle-tracking (FPT) method. The liquid particle
      counting method is commonly utilized to determine number-based size under flow
      conditions by converting the light scattering intensity of individual particles
      to size using the relationship between the size and light scattering intensity of
      a size standard material; however, the determined size depends strongly on the
      type of size standard material. In contrast, the developed FPT method can
      reliably determine the mean size of nanoparticles under flow conditions according
      to the Stokes-Einstein assumption by observing the Brownian motion of individual
      particles; therefore, this method does not require a calibration step using a
      size standard and can be applied to any type of material. To reliably size
      particles under flow conditions, we determined the flow velocity profile in a
      sample cell by extracting only the flow velocity from the particle motion. After
      determining the self-diffusion coefficient of each particle and subtracting the
      effect of the flow velocity, we successfully obtained a reliable mean size. The
      developed method could contribute to the application of microchannel
      reaction/synthesis devices using nanomaterials.

PMID- 29473408
TI  - Adaptation of Operational Parameters of Cold Atmospheric Plasma for in Vitro
      Treatment of Cancer Cells.
AB  - Cold atmospheric plasma (CAP), an ionized gas operated at near-ambient
      temperatures, has been introduced as a new therapeutic opportunity for treating
      cancers. The effectiveness of the therapy has been linked to CAP-generated
      reactive oxygen and nitrogen species such as hydrogen peroxide and nitrite. In
      this study, we monitor in real-time cancer cell response to CAP over the course
      of 48 h. The results demonstrate a correlation between cell viability, exposure
      time (30, 60, 90, and 180 s), and discharge voltage (3.16 and 3.71 kV), while
      stressing the likely therapeutic role of plasma-generated reactive species. A 30
      60 s increase in CAP exposure time and/or a discharge voltage adjustment from
      3.16 to 3.71 kV is consistently accompanied by a significant reduction in cell
      viability. Comparably, levels of hydrogen peroxide and nitrite vary as a function
      of voltage with elevated levels detected at the highest tested voltage condition
      of 3.71 kV. CAP ultimately initiates a reduction in cell viability and triggers
      apoptosis via damage to the mitochondrial membrane, while also deregulating
      protein synthesis. The findings presented in this study are discussed in the
      context of facilitating the development of an adaptive CAP platform which could
      improve treatment outcomes.

PMID- 29473411
TI  - Levamisole: a Common Adulterant in Cocaine Street Samples Hindering
      Electrochemical Detection of Cocaine.
AB  - The present work investigates the electrochemical determination of cocaine in the
      presence of levamisole, one of the most common adulterants found in cocaine
      street samples. Levamisole misleads cocaine color tests, giving a blue color
      (positive test) even in the absence of cocaine. Moreover, the electrochemical
      detection of cocaine is also affected by the presence of levamisole, with a
      suppression of the oxidation signal of cocaine. When levamisole is present in the
      sample in ratios higher than 1:1, the cocaine signal is no longer detected, thus
      leading to false negative results. Mass spectrometry and nuclear magnetic
      resonance were used to investigate if the signal suppression is due to the
      formation of a complex between cocaine and levamisole in bulk solution.
      Strategies to eliminate this suppressing effect are further suggested in this
      manuscript. In a first approach, the increase of the pH of the sample solution
      from pH 7 to pH 12 allowed the voltammetric determination of cocaine in the
      presence of levamisole in a concentration range from 10 to 5000 MUM at
      nonmodified graphite disposable electrodes with a detection limit of 5 MUM. In a
      second approach, the graphite electrode was cathodically pretreated, resulting in
      the presence of oxidation peaks of both cocaine and levamisole, with a detection
      limit for cocaine of 3 MUM over the linear range of concentrations from 10 to
      2500 MUM. Both these strategies have been successfully applied for the
      simultaneous detection of cocaine and levamisole in three street samples on
      unmodified graphite disposable electrodes.

PMID- 29473412
TI  - Novel Patterning Method for Nanomaterials and Its Application to Flexible Organic
      Light-Emitting Diodes.
AB  - We present a simple, low-cost, and scalable method to form various patterns of
      nanomaterials with different dimensions and shapes using capillary and
      centrifugal forces. The desired patterns were formed on the surfaces of
      poly(dimethylsiloxane) (PDMS) stamps, and the PDMS stamps were conformally
      contacted with the surfaces of flexible polymer substrates. Solutions of
      nanomaterials, such as metal nanowires and nanoparticles, were then drop-casted
      at one open end of the microchannels formed at the interface of the polymer
      substrate and PDMS stamp. The nanomaterial solutions penetrated the microchannels
      due to capillary force interactions between the surfaces and the fluid. The
      solvents of the nanomaterial solutions exfiltrated from the entrance of
      microchannels because of the coffee ring effect. Then, the solvent remaining in
      the microchannels was discharged by applying a centrifugal force by spinning the
      polymer substrate/PDMS stamp system. Because of the synergistic effect of the
      capillary force, coffee ring effect, and centrifugal force, uniform patterns of
      the nanomaterials with clearly defined edges were formed for a variety of pattern
      shapes and substrates. Furthermore, the direct patterning approach resulted in a
      significant reduction in the amount of wasted materials. Finally, flexible
      organic light-emitting diodes were successfully fabricated on the finely
      patterned nanowire electrodes.

PMID- 29473413
TI  - Expanding One-Pot Cell-Free Protein Synthesis and Immobilization for On-Demand
      Manufacturing of Biomaterials.
AB  - Fabrication of protein-based biomaterials is an arduous and time-consuming
      procedure with multiple steps. In this work, we describe a portable toolkit that
      integrates both cell-free protein synthesis (CFPS) and protein immobilization in
      one pot just by mixing DNA, solid materials, and a CFPS system. We have
      constructed a modular set of plasmids that fuse the N-terminus of superfolded
      green fluorescent protein (sGFP) with different peptide tags (poly(6X)Cys,
      poly(6X)His, and poly(6X)Lys), which drive the immobilization of the protein on
      the tailored material (agarose beads with different functionalities, gold
      nanorods, and silica nanoparticles). This system also enables the incorporation
      of azide-based amino acids into the nascent protein for its selective
      immobilization through copper-free click reactions. Finally, this technology has
      been expanded to the synthesis and immobilization of enzymes and antibody-binding
      proteins for the fabrication of functional biomaterials. This synthetic
      biological platform has emerged as a versatile tool for on-demand fabrication of
      therapeutic, diagnostic, and sensing biomaterials.

PMID- 29473414
TI  - Quantitative Rheometry of Thin Soft Materials Using the Quartz Crystal
      Microbalance with Dissipation.
AB  - In the inertial limit, the resonance frequency of the quartz crystal microbalance
      (QCM) is related to the coupled mass on the quartz sensor through the Sauerbrey
      expression that relates the mass to the change in resonance frequency. However,
      when the thickness of the film is sufficiently large, the relationship becomes
      more complicated and both the frequency and damping of the crystal resonance must
      be considered. In this regime, a rheological model of the material must be used
      to accurately extract the adhered film's thickness, shear modulus, and
      viscoelastic phase angle from the data. In the present work we examine the
      suitability of two viscoelastic models, a simple Voigt model ( Physica Scripta
      1999, 59, 391-396) and a more realistic power-law model ( Langmuir 2015, 31, 4008
      4017), to extract the rheological properties of a thermoresponsive hydrogel film.
      By changing temperature and initial dry film thickness of the gel, the operation
      of QCM was traversed from the Sauerbrey limit, where viscous losses do not impact
      the frequency, through the regime where the QCM response is sensitive to
      viscoelastic properties. The density-shear modulus and the viscoelastic phase
      angle from the two models are in good agreement when the shear wavelength ratio,
      d/lambda n, is in the range of 0.05-0.20, where d is the film thickness and
      lambda n is the wavelength of the mechanical shear wave at the nth harmonic. We
      further provide a framework for estimating the physical properties of soft
      materials in the megahertz regime by using the physical behavior of
      polyelectrolyte complexes. This provides the user with an approximate range of
      allowable film thicknesses for accurate viscoelastic analysis with either model,
      thus enabling better use of the QCM-D in soft materials research.

PMID- 29473415
TI  - Critical Nuclei Size, Rate, and Activation Energy of H2 Gas Nucleation.
AB  - Electrochemical measurements of the nucleation rate of individual H2 bubbles at
      the surface of Pt nanoelectrodes (radius = 7-41 nm) are used to determine the
      critical size and geometry of H2 nuclei leading to stable bubbles. Precise
      knowledge of the H2 concentration at the electrode surface, CH2surf, is obtained
      by controlled current reduction of H+ in a H2SO4 solution. Induction times of
      single-bubble nucleation events are measured by stepping the current, to control
      CH2surf, while monitoring the voltage. We find that gas nucleation follows a
      first-order rate process; a bubble spontaneously nucleates after a stochastic
      time delay, as indicated by a sudden voltage spike that results from impeded
      transport of H+ to the electrode. Hundreds of individual induction times, at
      different applied currents and using different Pt nanoelectrodes, are used to
      characterize the kinetics of phase nucleation. The rate of bubble nucleation
      increases by four orders of magnitude (0.3-2000 s-1) over a very small relative
      change in CH2surf (0.21-0.26 M, corresponding to a ~0.025 V increase in driving
      force). Classical nucleation theory yields thermodynamic radii of curvature for
      critical nuclei of 4.4 to 5.3 nm, corresponding to internal pressures of 330 to
      270 atm, and activation energies for nuclei formation of 14 to 26 kT,
      respectively. The dependence of nucleation rate on H2 concentration indicates
      that nucleation occurs by a heterogeneous mechanism, where the nuclei have a
      contact angle of ~150 degrees  with the electrode surface and contain between 35
      and 55 H2 molecules.

PMID- 29473416
TI  - Novel Electrochemical Paper-Based Immunocapture Assay for the Quantitative
      Determination of Ethinylestradiol in Water Samples.
AB  - We report a novel and innovative electrochemical paper-based immunocapture assay
      (EPIA) to address the need for ultrasensitive detection of emerging pollutants
      without regulatory status and whose effects on environment and human health are
      not completely yet understood. In particular, we present the application of this
      system toward highly sensitive detection of the emerging pollutant ethinyl
      estradiol (EE2). The EPIA approach is based on the use of paper microzones
      modified with silica nanoparticles (SNs) and anti-EE2 specific antibodies for
      capture and preconcentration of EE2 from river water samples. After the
      preconcentration procedure, the paper microzones are placed onto a screen-printed
      carbon electrode modified with electrochemically reduced graphene (RG). The bound
      EE2 is subsequently desorbed adding a diluted solution of sulfuric acid on the
      paper microzones. Finally, recovered EE2 is electrochemically detected by OSWV.
      The proposed novel methodology showed an appropriate LOD and linear range for the
      quantification of EE2 for water samples with different origins. The
      nonsophisticated equipment required, the adequate recovery values obtained (from
      97% to 104%, with a RSD less than 4.9%), and the appropriate LOD and linear range
      value (0.1 ng L-1 and 0.5-120 ng L-1, respectively) achieved by our immunocapture
      sensor present significant analytical figures of merit, particularly when the
      routine quantification of EE2 is considered. In addition, our system was based on
      electrochemical paper-based technology, which allows obtainment of portable, easy
      to-use, inexpensive, and disposable devices. The EPIA can also serve as a general
      purpose immunoassay platform applicable to quantitation of other drugs and
      emerging pollutants in environmental samples.

PMID- 29473417
TI  - Atomic Detail of Protein Folding Revealed by an Ab Initio Reappraisal of Circular
      Dichroism.
AB  - Circular dichroism (CD) is known to be an excellent tool for the determination of
      protein secondary structure due to fingerprint signatures of alpha and beta
      domains. However, CD spectra are also sensitive to the 3D arrangement of the
      chain as a result of the excitonic nature of additional signals due to the
      aromatic residues. This double sensitivity, when extended to time-resolved
      experiments, should allow protein folding to be monitored with high spatial
      resolution. To date, the exploitation of this very appealing idea has been
      limited, due to the difficulty in relating the observed spectral evolution to
      specific configurations of the chain. Here, we demonstrate that the combination
      of atomistic molecular dynamics simulations of the folding pathways with a
      quantum chemical evaluation of the excitonic spectra provides the missing key.
      This is exemplified for the folding of canine milk lysozyme protein.

PMID- 29473418
TI  - Development and Comparison of Air Pollution Exposure Surfaces Derived from On
      Road Mobile Monitoring and Short-Term Stationary Sidewalk Measurements.
AB  - Land-use regression (LUR) models of air pollutants are frequently developed on
      the basis of short-term stationary or mobile monitoring approaches, which raises
      the question of whether these two data collection protocols lead to similar
      exposure surfaces. In this study, we measured ultrafine particles (UFP) and black
      carbon (BC) concentrations in Toronto during summer 2016, using two short-term
      data collection approaches: mobile, involving 3023 road segments sampled on
      bicycles, and stationary, involving 92 sidewalk locations. We developed four LUR
      models and exposure surfaces, for the two pollutants and measurement protocols.
      Coefficients of determination ( R2) varied from 0.434 to 0.525. Various small
      scale traffic variables were included in the mobile LUR. Pearson correlation
      coefficients between the mobile and stationary surfaces were 0.23 for UFP and
      0.49 for BC. We also compared the two surfaces using personal exposures from a
      panel study in Toronto conducted during the same period. The personal exposures
      differed from the outdoor exposures derived from the combination of GPS
      information and exposure surfaces. For UFP, the median for personal outdoor
      exposure was 26 344 part/cm3, while the cycling and stationary surfaces predicted
      medians of 31 201 and 19 057 part/cm3. Similar trends were observed for BC, with
      median exposures of 1764 (personal), 1799 (cycling), and 1469 ng/m3 (stationary).

PMID- 29473419
TI  - Application of Cesium on the Restriction of Precursor Crystallization for Highly
      Reproducible Perovskite Solar Cells Exceeding 20% Efficiency.
AB  - In this study, we systematically explored the mixed-cation perovskite Cs
      x(MA0.4FA0.6)1- xPbI3 fabricated via sequential introduction of cations. The
      details of the effects of Cs+ on the fabrication and performance of inorganic
      organic mixed-cation perovskite solar cells examined in detail in this study are
      beyond the normal understanding of the adjusting band gap. It is found that a
      combined intercalation of Cs+ and dimethyl sulfoxide (DMSO) in PbI2-DMSO
      precursor film formed a strong and steady coordinated intermediate phase to
      retard PbI2 crystallization, suppress yellow nonperovskite delta-phase, and
      obtain a highly reproducible perovskite film with less defects and larger grains.
      The Cs-contained triple-cation-mixed perovskite Cs0.1(MA0.4FA0.6)0.9PbI3 devices
      yield over 20% reproducible efficiencies, superior stabilities, and fill factors
      of around 0.8 with a very narrow distribution.

PMID- 29473420
TI  - Quantum Dots Formed in Three-dimensional Dirac Semimetal Cd3As2 Nanowires.
AB  - We demonstrate quantum dot (QD) formation in three-dimensional Dirac semimetal
      Cd3As2 nanowires using two electrostatically tuned p-n junctions with a gate and
      magnetic fields. The linear conductance measured as a function of gate voltage
      under high magnetic fields is strongly suppressed at the Dirac point close to
      zero conductance, showing strong conductance oscillations. Remarkably, in this
      regime, the Cd3As2 nanowire device exhibits Coulomb diamond features, indicating
      that a clean single QD forms in the Dirac semimetal nanowire. Our results show
      that a p-type QD can be formed between two n-type leads underneath metal contacts
      in the nanowire by applying gate voltages under strong magnetic fields. Analysis
      of the quantum confinement in the gapless band structure confirms that p-n
      junctions formed between the p-type QD and two neighboring n-type leads under
      high magnetic fields behave as resistive tunnel barriers due to cyclotron motion,
      resulting in the suppression of Klein tunneling. The p-type QD with magnetic
      field-induced confinement shows a single hole filling. Our results will open up a
      route to quantum devices such as QDs or quantum point contacts based on Dirac and
      Weyl semimetals.

PMID- 29473421
TI  - Assessing Preventable Harms in the Intensive Care Unit: Data From a Tertiary Care
      Academic Medical Institution.

PMID- 29473422
TI  - Linear and Nonlinear Thermal Lens Signal of the (Deltanu = 6) C-H Vibrational
      Overtone of Naphthalene in Liquid Solutions of n-Hexane.
AB  - The thermal lens technique is applied to vibrational overtone spectroscopy of
      solutions of naphthalene (C10H8) in liquid hexane. The C-H fifth vibrational
      (Deltanu = 6) overtone spectrum of C10H8 is detected at room temperature for mole
      fractions from 0.08 to 19 * 10-6 using n-C6H14 as solvent. By detecting the
      absorption band in a 19 ppm (parts per million) solution, the peak absorption of
      the signal is approximately (2.2 +/- 0.3) * 10-7 cm-1. A plot of normalized
      integrated intensity as a function of the mole fraction of naphthalene in
      solution reveals a dependence of the magnitude of the signal with the probe laser
      wavelength. If the wavelength of the probe laser is 568 nm, the thermal lens
      signal (TLS) is linear as a function of the mole fraction of the solution. When
      the wavelength of the probe laser is 488 nm, the TLS is nonlinear as a function
      of the concentration. Three different models of nonlinear absorption are
      discussed. A two-color absorption model that includes the simultaneous absorption
      of the pump and probe lasers could explain the enhanced magnitude and the
      nonlinear behavior of the TLS for solutions of mole fraction < 0.1%.

PMID- 29473423
TI  - Implementation of Proton Pump Inhibitor Deprescription Protocol in Geriatric
      Residents.
AB  - BACKGROUND: Deprescribing is a recommended intervention to reduce morbidity and
      mortality caused by polypharmacy in older residents. However, a lack of definite
      deprescription guidelines and evidence of clinically meaningful outcomes
      complicates or precludes the practicality of such an approach. OBJECTIVE: The
      objective of the present pilot study is to establish and implement a stepwise
      taper protocol that can potentially minimize overuse of proton pump inhibitors in
      a safe, effective, and feasible manner in the nursing home. METHODS: Proton pump
      inhibitor dosage was reduced by half every 3 weeks until the lowest dose was
      reached; thereafter, the frequency was changed to every other day for 3 weeks, if
      tolerated. Subsequently, histamine receptor antagonists replaced proton pump
      inhibitors and followed the same deprescription regimen until discontinuation.
      Patient-specific interventions also included reassessment of therapeutic agents
      and dosage forms for more tolerable alternatives to facilitate deprescription
      efforts and minimize gastric ulceration or discomfort. RESULTS: The pilot study
      enrolled 10 patients (average age 65.6 years, medication burden 16.8 units, and
      antisecretory duration 37.5 months). Physicians accepted >95% of interventions,
      and 90% of patients achieved cessation at 12 weeks. Post cessation, none of the
      patients needed antacid, prokinetic, or antisecretory agents at 4 weeks.
      Difficulties in order interpretation and transcription among nurses as well as
      order entry and calculations among pharmacists were noted. CONCLUSIONS: The
      present pilot study added to the growing body of evidence that gradual
      deprescription of antisecretory medications is feasible. Nonetheless, the pilot
      design precludes any conclusions about safety and efficacy of the intervention.

PMID- 29473424
TI  - European Society of Cardiology Council for Cardiology Practice worldwide survey
      of transcatheter aortic valve implantation beliefs and practices.
AB  - Background Transcatheter aortic valve implantation (TAVI) continues to gain
      popularity in the management of patients with severe aortic stenosis (SAS).
      Distribution of resources to maximise appropriate use remains a priority. Design
      & methods To determine the current perceptions and behaviours regarding SAS
      patient management, an 18-point multiple-choice questionnaire was distributed to
      European Society of Cardiology (ESC) Council for Cardiology Practice (CCP) e
      journal and/or electronic newsletter subscribers. Respondents to all questions
      were considered. Sub-analyses based on respondent age, practice setting and
      geographical location were performed. Results Of 1245 full respondents, 41.5%
      were aged >= 51 years, 22.7% were aged 41-50 years and 35.8% were aged <= 40
      years. The majority were located in Europe (77.5%), followed by Asia/Oceania
      (11.6%), America (7.6%) and Africa (3.4%). In-hospital and out-of-hospital
      cardiologists accounted for 57.4% of and 28.5% of the sample, respectively, with
      the remainder being general practitioners/other. The majority of respondents
      (70.1%) claimed to diagnose between one and five cases of SAS per month. Free
      access to TAVI was reported by 41.2%, being less common for those aged <= 40
      years (32.7%; p < 0.001), those located in Asia/Oceania, America and Africa
      (20.1%, 18.1% and 2.4%, respectively; p < 0.01 in each case) and in-hospital
      compared to out-of-hospital cardiologists (35.7% vs. 54.5%, respectively; p <
      0.001). The most common reason for not referring a patient for an aortic valve
      intervention was assessment that the patient was high risk/non-operable (55.5%),
      followed by short life expectancy (30.5%). The most common reason for referring a
      patient for TAVI over surgical replacement was surgical risk score (56.9%). The
      most commonly perceived main complication of TAVI was stroke (28.9%), while the
      most frequently selected main benefit was improvement in quality of life (37.2%).
      A high proportion (82.5%) of respondents believed that TAVI is/may become a
      viable option for lower-risk SAS patients in future. Conclusion The population of
      potential TAVI is significant worldwide, with key barriers to referral being
      access limitations and poor physician education. Strategies to minimise these
      factors are paramount.

PMID- 29473425
TI  - Characterisation of nutraceutical compounds from different parts of particular
      species of Citrus sinensis 'Ovale Calabrese' by UHPLC-UV-ESI-HRMS.
AB  - Consumers are aware of diet causing health problems and therefore there is an
      increased demand for natural ingredients that are expected to be safe and health
      promoting. Many of these compounds belong to the class of flavonoids and can be
      divided into these five groups: flavanones, flavones, flavonols, flavanols,
      isoflavones and anthocyanidins. Extracts from citrus fruits are usually used as
      functional ingredients for several products. The aim of this paper was to develop
      an UHPLC-UV-ESI-HRMS method to define the metabolite profile of different parts
      of citrus fruit, of a particular cultivar called 'Ovale Calabrese', and in its
      main by-products. The high resolution mass spectrometry analysis allowed the
      identification of 27 compounds belonging to the classes of flavonoids and
      terpenoids. The high contents of phytochemical compounds, reveal the potential
      use of the 'Ovale Calabrese' as a rich source of nutraceutical compounds.

PMID- 29473426
TI  - Factors associated with informant-reported cognitive decline in older adults: A
      systemised literature review.
AB  - Background Dementia diagnoses are typically made where there is a significant,
      progressive decline in cognitive functioning. Evidence of such decline is
      increasingly established through information provided by informants. However,
      some studies demonstrate that informant reports may not always be accurate and
      may be biased by extraneous factors. This review aimed to elucidate factors that
      have been identified as potentially having some influence on informant reports of
      cognitive decline. Method A search of PsychInfo, ASSIA, PubMed and Web of Science
      databases identified 13 peer-reviewed studies that met criteria for inclusion in
      the review. Results Reviewed studies provide some evidence for associations
      between informant-reported cognitive decline and demographic characteristics
      (patient age, education, ethnicity and informant gender), clinical factors
      (dementia severity, diagnosis, behavioural disturbance, everyday functioning) and
      psychological factors (patient depressive symptoms and neuroticism, informant
      psychological distress and burden). Several methodological limitations of the
      evidence base were identified. Conclusion Findings suggest that informant
      reported cognitive decline may not always be wholly reliable in that information
      holds potential to be influenced by both patient and informant characteristics.
      Clinical and empirical implications are discussed.

PMID- 29473427
TI  - Glucocorticoid sensitivity and inflammatory status of peripheral blood
      mononuclear cells in patients with coronary artery disease.
AB  - OBJECTIVE: Mechanisms behind sustained inflammation in patients with coronary
      artery disease (CAD) are not clarified but hypothalamus-pituitary-adrenal (HPA)
      axis dysfunction may have a role. Here, we investigated whether inflammatory
      status of peripheral blood mononuclear cells (PBMCs) was associated with altered
      glucocorticoid sensitivity in CAD patients. METHODS: In 55 CAD patients and 30
      controls, mRNA levels of GR-alpha, GR-beta, NF-kappaB, IkappaBalpha, MMP-9 and
      TIMP-1 were measured in PBMCs. Suppressive effects of dexamethasone on GR-alpha,
      GR-beta, NF-kappaB, IkappaBalpha, MMP-9 and TIMP-1 mRNA levels were assessed in
      PBMCs ex vivo. Salivary cortisol was repeatedly measured over 3 days. RESULTS: GR
      alpha mRNA levels were higher in CAD patients than in controls, 0.50 (0.38-0.59)
      versus 0.26 (0.18-0.37), p < .001, while GR-beta mRNA levels were equally low in
      both groups. GR-alpha mRNA expression was associated with inflammatory gene
      expression and, also, with flatter diurnal cortisol rhythm. In both patients and
      controls, dexamethasone suppressed gene expression of NF-kappaB, IkappaBalpha,
      MMP-9 and TIMP-1 (p < .001). Dexamethasone also reduced GR-alpha mRNA levels (p <
      .001), while LPS increased it (p < .001). CONCLUSIONS: PBMCs from CAD patients
      displayed an inflammatory gene expression profile. This was not explained by
      reduced glucocorticoid sensitivity. Instead, inflammation was associated with
      increased expression of GR-alpha mRNA, suggesting a hypocortisolemic state. Key
      messages   * Peripheral blood mononuclear cells from patients with coronary
      artery disease (CAD) display an inflammatory gene expression profile.   * This
      inflammatory state cannot be explained by reduced glucocorticoid sensitivity in
      CAD patients.   * Instead, the inflammatory gene expression profile is associated
      with upregulated levels of glucocorticoid receptor-alpha mRNA, suggesting a
      hypocortisolemic state.

PMID- 29473428
TI  - A patent review of IDO1 inhibitors for cancer.
AB  - INTRODUCTION: Indoleamine 2,3-dioxygenase 1 (IDO1) is overexpressed by cancer
      cells and the antigen presenting dendritic cells in the tumor microenvironment
      (TME). Activation of IDO1 depletes tryptophan and produces kynurenine, which
      induces T cell anergy and suppresses tumor control by the immune system. When
      combined with an immune checkpoint inhibitor, IDO1 inhibitors have shown
      promising anticancer activity in preclinical tumor models as well as in early
      stage clinical trials. Areas covered: IDO1 inhibitors disclosed in the patent
      literature from 2013-2017 are categorized, when applicable, according to their
      structural similarity to the clinical development candidates indoximod and PF
      06840003, navoximod, epacadostat, KHK2455 and aryl-1,2-diamines, and BMS-986205
      among others, respectively. Representative structures and their IDO1 inhibitory
      activity are presented to highlight the novelty and activity. Finally, the
      reported cocrystal structures were analyzed to provide insights for inhibitor
      enzyme interactions and guidance for the design and discovery of next generation
      inhibitors. Expert opinion: This review demonstrates that the structural
      diversity of new IDO1 inhibitors could be expanded via a number of approaches.

PMID- 29473429
TI  - A safety evaluation of budesonide MMX for the treatment of ulcerative colitis.
AB  - INTRODUCTION: Budesonide belongs to low-bioavailability steroids class. A novel
      oral formulation of budesonide, which uses the Multi-Matrix System (MMX) for
      delivering drugs to the colon, is now available as a possible treatment of
      ulcerative colitis patients intolerant or not-responding to first-line therapy
      with 5-ASA. Areas covered: in this review we present information about the
      development and the use of budesonide MMX and we provide data about its mechanism
      of action as well as, pharmacodynamics and pharmacokynetics. Moreover, we present
      the available literature data about the efficacy and, mainly, the safety of
      budesonide-MMX. Expert opinion: budesonide-MMX is a new therapeutic option in
      mild-to-moderate UC patients. Its good safety profile in clinical trials
      undoubtedly represents a strength for a possible wide use in clinical practice,
      mainly if it will be confirmed by post-marketing data. Other indications, such as
      treatment of colonic Crohn's disease, could theoretically be considered, if
      sustained by reliable scientific data.

PMID- 29473430
TI  - Lymphomatoid granulomatosis and large granular lymphocyte leukemia, a rare
      association of two lymphoproliferative disorders.

PMID- 29473431
TI  - Enhancer of zeste homolog 2 (EZH2) inhibitors.
AB  - Dysregulation of the histone methyltransferase EZH2 plays a critical role in the
      development of a variety of malignancies including B-cell lymphomas. As a result,
      a series of small molecule inhibitors of EZH2 have been developed and studied in
      the pre-clinical setting. Three EZH2 inhibitors: tazemetostat (EPZ-6438),
      GSK2816126 and CPI-1205 have moved into phase I/phase II clinical trials in
      patients with non-Hodgkin lymphoma and genetically defined solid tumors. Early
      data from the tazemetostat trials indicate an acceptable safety profile and early
      signs of activity in diffuse large B-cell lymphoma and follicular lymphoma,
      including patients with EZH2 wild-type and mutant tumors. In this review, we
      present the rationale, key pre-clinical and early clinical findings of small
      molecule EZH2 inhibitors for use in lymphoma as well as future challenges and
      potential opportunities for combination therapies.

PMID- 29473433
TI  - Acute myeloid leukemia developed in Ph- cells with MLL gene amplification in a
      patient with chronic myelogenous leukemia.

PMID- 29473432
TI  - Human neutrophil lipocalin (HNL) as a biomarker of acute infections.
AB  - The early and accurate discrimination between bacterial and viral causes of acute
      infections is the key to a better use of antibiotics and will help slow down the
      fast-growing resistance to commonly used antibiotics. This discrimination is in
      the vast majority of cases possible to achieve by blood assay of the biomarker
      human neutrophil lipocalin (HNL), which we showed to be uniquely increased in
      patients suffering from bacterial infections. In serum, sensitivities and
      specificities of >90% are achieved in both adults and children. In order to
      eliminate the need to produce serum, a whole-blood assay with an assay time of
      <10 min was developed in which blood neutrophils are activated to release HNL.
      The diagnostic accuracy of this assay also showed sensitivities and specificities
      of >90% in most infectious diseases and was clearly superior to contemporary
      assays such as blood neutrophil counts, C-reactive protein, procalcitonin, and
      expression of CD64 on blood neutrophils. This format lends itself to the
      development of a point-of-care HNL assay and will be a major step forward to
      accomplish the goal of accurately diagnosing patients with symptoms of acute
      infections within 10 min at the emergency room or at the doctor's office.

PMID- 29473434
TI  - 4-Methylcatechol stimulates apoptosis and reduces insulin secretion by decreasing
      betacellulin and inhibin beta-A in INS-1 beta-cells.
AB  - Insulinoma INS-1 cell line is a pancreatic beta cell tumor which is characterized
      with high insulin content and secretion in response to increasing glucose levels.
      4-Methylcatechol (4-MC) is a metabolite of quercetin, which is known as a
      potential drug for inhibition of tumorigenesis. The aim of this study was to
      determine the applying doses of 4-methylcatechol (4-MC) for triggening cell death
      and decreasing the cell function of rat insulinoma INS-1 beta cells. The rate of
      apoptosis and the amount of insulin in the cell and the secretions were
      determined by the ELISA method. Betacellulin (BTC) and inhibin beta-A amounts in
      both the cell and the glucose induced secretion were investigated by Western
      blotting. Furthermore, BTC, Inhibin beta-A, Ins1, Ins2, and GLUT2 gene expression
      levels were determined by the by the real-time quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) method. We noted a significant decrease in
      cell viability, while an increase in apoptotic cell death by 4-MC treatment. It
      caused a decrease in the secretion of BTC, expressions of both BTC and inhibin
      beta-A. We showed a decrease in the expressions of Ins1 and GLUT2, while there is
      no alteration in the level of insulin protein. Insulin secretion levels increased
      in INS-1 cells given 4-MC by basal glucose concentration while they did not
      response to high concentration of glucose, which indicates that 4-MC disrupts the
      functionality of INS-1 cells. These results revealed that 4-MC induces apoptosis
      and decreases insulin secretion by reducing BTC and inhibin beta-A in insulinoma
      INS-1 cells. Thus, 4-MC may be offered as a potential molecule for treatment of
      insulinoma.

PMID- 29473435
TI  - A new neolignan from the thorns of Gleditsia japonica var. delavayi.
AB  - A new neolignan, 5-(3"-acetoxypropyl)-2-(4'-hydroxy-3'-methoxyphenyl)-7-methoxy-3
      methylbenzofuran (1) along with nine analogues were isolated from the thorns of
      Gleditsia japonica var. delavayi by solvent extraction and repeated column
      chromatography. Their structures were elucidated by means of extensive
      spectroscopic analysis including 1D, 2D-NMR techniques and HR-ESIMS. All the
      isolates were reported for the first time from this species.

PMID- 29473436
TI  - Nivolumab in the treatment of microsatellite instability high metastatic
      colorectal cancer.
AB  - Nivolumab is a PD-1 inhibitor approved for the use in treatment of multiple tumor
      types (such as melanoma, non-small-cell lung cancer, renal cell carcinoma,
      urothelial cancer and Hodgkin's lymphoma). In July 2017, the US FDA granted
      accelerated approval of this agent for the treatment of metastatic colorectal
      cancer patients whose tumor harbors deficient mismatch repair, or microsatellite
      instability high and have progressed on conventional chemotherapy. In this
      review, we will discuss the use, efficacy, and safety of this agent in
      microsatellite-instability high metastatic colorectal cancer.

PMID- 29473437
TI  - Anti-breast cancer triterpenoid saponins from the thorns of Gleditsia sinensis.
AB  - One new triterpenoid saponin (1), as well as six known ones (2-7), were isolated
      from the ethanol extract of the thorns of Gleditsia sinensis. Their structures
      were elucidated by extensive spectroscopic analysis in conjunction with chemical
      evidence. Cytotoxic activity of compounds 1-6 was evaluated against human breast
      cancer MCF 7 cells in vitro by the MTT method. Our results revealed moderate
      activities for compounds 1-6 with IC50 values of 18.43, 30.47, 18.46, 10.02,
      30.76, and 17.32 MUM, respectively. Furthermore, compounds 1, 3, 4, and 6 induced
      apoptosis in MCF 7 cell, with 1 and 6 causing late apoptosis of MCF 7 cells,
      while 3 and 4 acting oppositely.

PMID- 29473438
TI  - CRISPR and personalized Treg therapy: new insights into the treatment of
      rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA), as one of the most disabling autoimmune
      diseases, is a common health problem that progressively reduces the life quality
      of patients. Although various biologics have been introduced for RA, attempts to
      establish an efficient long-term therapies failed due to the heterogeneity of
      this disease. METHODS: In the last decade, immunomodulatory approaches such as T
      cell adoptive therapy have been developed for controlling autoimmunity.
      Regulatory T cells (Tregs), the major self-tolerance mediator, are crucial for
      down-regulation of aberrant immune stimulations. Hence, recruiting ex vivo Tregs
      emerged as a promising therapy for a variety of autoimmune diseases. RESULTS: The
      major bottleneck of the Treg adoptive therapy is maintaining the in vivo
      stability and plasticity of these fascinating cells. Recent progress in genome
      editing technology clustered regularly interspaced short palindromic repeats
      (CRISPR) in combination with CRISPR-associated (Cas) 9 system provided a new
      solution for this bottleneck. CONCLUSIONS: The present paper discusses RA
      pathogenesis and the potential application of new developments in CRISPR-mediated
      Treg genome editing in personalized therapy of RA.

PMID- 29473439
TI  - Welfare State Replacements: Deinstitutionalization, Privatization and the
      Outsourcing to Immigrant Women Enterprise.
AB  - The U.S. government has a long tradition of providing direct care services to
      many of its most vulnerable citizens through market-based solutions and
      subsidized private entities. The privatized welfare state has led to the
      continued displacement of some of our most disenfranchised groups in need of long
      term care. Situated after the U.S. deinstitutionalization era, this is the first
      study to examine how immigrant Filipino women emerged as owners of de facto
      mental health care facilities that cater to the displaced, impoverished, severely
      mentally ill population. These immigrant women-owned businesses serve as welfare
      state replacements, overseeing the health and illness of these individuals by
      providing housing, custodial care, and medical services after the massive closure
      of state mental hospitals that occurred between 1955 and 1980. This study
      explains the onset of these businesses and the challenges that one immigrant
      group faces as owners, the meanings of care associated with their de facto mental
      health care enterprises, and the conditions under which they have operated for
      more than 40 years.

PMID- 29473440
TI  - Goal setting in paediatric rehabilitation for children with motor disabilities: a
      scoping review.
AB  - OBJECTIVES: The three objectives of this scoping review were to (1) identify key
      conceptual/theoretical frameworks and the extent to which they are used to inform
      goal setting related to rehabilitation goal setting with children with motor
      disabilities, (2) describe research that has evaluated goal setting processes and
      outcomes, and (3) summarize the purposes of goal setting described in paediatric
      rehabilitation literature. METHODS: The scoping review process described by
      Arksey and O'Malley was used to guide article selection and data extraction.
      RESULTS: A total of 62 articles were included in the final review. While the
      concept of family-centered care was well represented, theoretical frameworks
      specific to goal setting (i.e. goal setting theory described by Locke and Latham,
      mastery motivation, social cognitive, personal construct, and self-determination
      theories) were rarely addressed. No articles reviewed addressed prominent
      behavior change theory. With the exception of the description of tools
      specifically designed for use with children, the role of the child in the goal
      setting process was generally absent or not well described. Few studies ( n = 6)
      discussed the linkage between goals and intervention strategies explicitly. Only
      two studies in the review evaluated outcomes associated with goal setting. The
      primary purpose for goal setting identified in the literature was to develop
      goals that are meaningful to families ( n = 49). CONCLUSION: The results
      highlight significant gaps in the literature explicating a sound theoretical
      basis for goal setting in paediatric rehabilitation and research evaluating the
      effects of goal qualities and goal setting processes on the achievement of
      meaningful outcomes.

PMID- 29473441
TI  - Item analysis of the Spanish version of the Boston Naming Test with a Spanish
      speaking adult population from Colombia.
AB  - OBJECTIVE: The Boston Naming Test (BNT) is a widely used measure of confrontation
      naming ability that has been criticized for its questionable construct validity
      for non-English speakers. This study investigated item difficulty and construct
      validity of the Spanish version of the BNT to assess cultural and linguistic
      impact on performance. METHODS: Subjects were 1298 healthy Spanish speaking
      adults from Colombia. They were administered the 60- and 15-item Spanish version
      of the BNT. A Rasch analysis was computed to assess dimensionality, item
      hierarchy, targeting, reliability, and item fit. RESULTS: Both versions of the
      BNT satisfied requirements for unidimensionality. Although internal consistency
      was excellent for the 60-item BNT, order of difficulty did not increase
      consistently with item number and there were a number of items that did not fit
      the Rasch model. For the 15-item BNT, a total of 5 items changed position on the
      item hierarchy with 7 poor fitting items. Internal consistency was acceptable.
      CONCLUSIONS: Construct validity of the BNT remains a concern when it is
      administered to non-English speaking populations. Similar to previous findings,
      the order of item presentation did not correspond with increasing item
      difficulty, and both versions were inadequate at assessing high naming ability.

PMID- 29473443
TI  - Pesticide Use, Poisoning, and Knowledge and Unsafe Occupational Practices in
      Thailand.
AB  - The agricultural system in Thailand has shifted from a traditional to a
      commercial agricultural system. Pesticides have been imported into Thailand to
      increase agricultural productivity, resulting in adverse health effects for
      farmers and consumers. However, the scientific data available in Thailand are
      limited and inconsistent. Thus, this article reviews research studies regarding
      pesticide use, poisoning, and knowledge and unsafe occupational practices in
      Thailand over the last decade. This article also makes recommendations for future
      policies. Research studies conducted in Thailand during 2006-2017 were reviewed
      and summarized. Overall, there are several solutions to address the pesticide
      problem, such as rigorous legislation and regulations, campaigns for reducing
      pesticide use, education, and training. The Thai government has an important role
      in making policies and regulations and encouraging all agricultural activities to
      be sustainable.

PMID- 29473444
TI  - Bad is Stronger Than Good for Stigmatized, but Not Admired Outgroups: Meta
      Analytical Tests of Intergroup Valence Asymmetry in Individual-to-Group
      Generalization Experiments.
AB  - Theories of risk aversion, epistemic defense, and ingroup enhancement converge in
      predicting greater impact of negative (vs. positive) experiences with outgroup
      members on generalized evaluations of stigmatized outgroups. However, they
      diverge in predictions for admired outgroups. Past tests have focused on negative
      outgroups using correlational designs without a control group. Consequently, they
      have not distinguished between alternative explanations or ascertained the
      direction of causality/generalization, and they have suffered from self-selection
      biases. These limitations were redressed by a meta-analysis of experimental
      research on individual-to-group generalization with positive and negative
      outgroups (59 tests; 3,012 participants). Controlling for modest confounds, the
      meta-analysis found a generalization advantage of negative experiences for
      stigmatized outgroups and a generalization advantage of positive experiences for
      admired outgroups. These results highlight the centrality of valenced
      expectations about outgroups, consistent with epistemic defense and ingroup
      enhancement and inconsistent with risk aversion. Implications for positive
      changes in intergroup dynamics are discussed.

PMID- 29473442
TI  - HU protein is involved in intracellular growth and full virulence of Francisella
      tularensis.
AB  - The nucleoid-associated HU proteins are small abundant DNA-binding proteins in
      bacterial cell which play an important role in the initiation of DNA replication,
      cell division, SOS response, control of gene expression and recombination. HU
      proteins bind to double stranded DNA non-specifically, but they exhibit high
      affinity to abnormal DNA structures as four-way junctions, gaps or nicks, which
      are generated during DNA damage. In many pathogens HU proteins regulate
      expression of genes involved in metabolism and virulence. Here, we show that the
      Francisella tularensis subsp. holarctica gene locus FTS_0886 codes for functional
      HU protein which is essential for full Francisella virulence and its resistance
      to oxidative stress. Further, our results demonstrate that the recombinant FtHU
      protein binds to double stranded DNA and protects it against free hydroxyl
      radicals generated via Fenton's reaction. Eventually, using an iTRAQ approach we
      identified proteins levels of which are affected by the deletion of hupB, among
      them for example Francisella pathogenicity island (FPI) proteins. The pleiotropic
      role of HU protein classifies it as a potential target for the development of
      therapeutics against tularemia.

PMID- 29473445
TI  - The determination of monomers and oligomers from polyester-based can coatings
      into foodstuffs over extended storage periods.
AB  - The polymeric coating used in metal packaging such as cans for foods and
      beverages may contain residual amounts of monomers used in the production of the
      coating, as well as unreacted linear and cyclic oligomers. Traditionally,
      although designed for use with plastic food contact materials, food simulants
      have been used to determine the migration of monomers from coatings into
      foodstuffs. More recently, food simulants have also been used to determine
      oligomeric species migrating from can coatings. In the work reported here, the
      migration of both monomers and oligomers from polyester-based can coatings into
      food simulants and foodstuffs, some of which were towards the end of their shelf
      life, is compared. The concentrations of monomers and selected oligomers in
      canned foods at the end of their shelf life were found to be significantly lower
      than those in food simulants, which in turn was lower than those in the
      extraction solvent acetonitrile.

PMID- 29473446
TI  - Predicting shoulder function after constraint-induced movement therapy: a
      retrospective cohort study.
AB  - Background Several predictors have been associated with upper extremity (UE)
      recovery after stroke, but characteristics that predict shoulder function after
      constraint-induced movement therapy (CIMT) have not yet been identified.
      Objectives To identify predictors associated with satisfactory shoulder function
      in patients with reduced shoulder function at admission to CIMT. Methods One
      hundred and seventy five patients were treated using CIMT while in a specialized
      inpatient hospital. Satisfactory shoulder function was defined according to the
      functional ability scale of the Wolf Motor Function test. Predictors of
      satisfactory shoulder function after CIMT were identified using multivariable
      logistic regression. Results Better distal arm function and good proximal
      shoulder function on admission to CIMT were strong predictors of satisfactory
      shoulder function, while age and time of admission to CIMT since stroke were not.
      Seventeen percent of all CIMT-participants with reduced shoulder function pre
      CIMT reached a level of satisfactory shoulder function after CIMT. Discussion A
      substantial part of patients with reduced shoulder function reached a level of
      satisfactory shoulder function after CIMT. Intensive CIMT training, comprising
      tasks that require both distal and proximal UE function, may increase shoulder
      function in patients with a potential functional reserve.

PMID- 29473447
TI  - U0126 protects hippocampal CA1 neurons against forebrain ischemia-induced
      apoptosis via the ERK1/2 signaling pathway and NMDA receptors.
AB  - OBJECTIVE: Cerebral ischemia can trigger the ERK1/2 signaling cascade that
      enables the brain to adapt to ischemic injury. However, the mechanism of ERK1/2
      in ischemic brain injury remains unclear. The aim of this study was to examine
      the roles of the ERK1/2 signaling pathway and NMDA receptors in the apoptosis of
      CA1 pyramidal neurons after ischemia/reperfusion (I/R). METHODS: Male Wistar rats
      were subjected to a sham or transient forebrain ischemia procedure. Animals
      received the intracerebroventricular injection of U0126 (5 MUl, 0.2 MUg/MUl) or
      vehicle 30 min before ischemia. Homogenates of the hippocampal CA1 field were
      obtained from sham-operated and ischemic rats 6, 12 or 48 h after
      ischemia/reperfusion (n = 6 per group) and then subjected to Western blotting
      analysis and TUNEL staining. Caspase-3 activity was assayed with a colorimetric
      assay kit. RESULTS: We found that the phosphorylation level of ERK1/2 is
      increased in the CA1 region following transient I/R. Blocking the ERK1/2
      signaling pathway by administration U0126 attenuated apoptotic neuronal cell
      death via inhibition of NMDA receptors. CONCLUSION: These findings suggest a
      novel mechanism by which the ERK1/2 signaling pathway affects the post-I/R
      apoptosis of CA1 pyramidal neurons, which will provide a therapeutic target for
      the treatment of stroke.

PMID- 29473448
TI  - Demographic and clinical features do not affect the outcome of combined
      endovenous therapy to treat leg swelling.
AB  - Background There have been well-documented implications of race/ethnicity on the
      outcome of various vascular diseases, yet there are limited data on risk factors
      and outcome of lower limb swelling. While many patients improve with endovenous
      therapy (thermal ablation or iliac vein stenting), some patients' symptoms
      persist. The goal of this study was to identify clinical factors including
      race/ethnicity related to persistent leg swelling after treatment with both iliac
      vein stenting and thermal ablation. Methods From February 2012 to February 2014,
      this observational study analyzed data for 173 patients with chronic venous
      insufficiency who underwent both iliac vein stent placement as well as thermal
      ablation (radiofrequency ablation or endovenous laser ablation). All procedures
      of the thermal ablations and the iliac vein stenting were staged. Iliac vein
      stenosis was identified using intravascular ultrasound of the iliofemoral venous
      segment showing >50% cross-sectional area or diameter reduction. The patients
      were queried to the resolution of their leg swelling after both procedures were
      performed. The resolution of swelling was correlated with age, gender, presenting
      sign according to CEAP classification, race/ethnicity and degree of iliac vein
      stenosis. Patients were categorized by Caucasians ( n = 97), African Americans (
      n = 27), or Hispanics ( n = 49). Statistical analysis performed using Chi-square
      and Student's t test. Results Of the total 173 patients who underwent both
      endovenous closure and iliac vein stent placements, 117 (67.6%) patients were
      women. The average age was 67 (+/-13 SD) years. The average pain score was 2.9(+/
      3.1 SD). The average degree of iliac vein stenosis was 66.5(+/-13.3 SD). About
      56.1% were Caucasians, 15.6% were African Americans, and 28.3% were Hispanics.
      The number of patients with iliac vein stent thrombosis was 2. One hundred fifty
      two (87.9%) patients stated that they had improvement in swelling after combined
      procedures, 100 (65.8%) patients were women. The average age was 67.3 (+/-13 SD)
      years. The average pain score was 2.9 (+/-3.1 SD). The average degree of iliac
      vein stenosis was 67.3% (+/-12.8 SD). About 56.6% were Caucasians, 15.1% were
      African Americans, and 28.3% were Hispanics. The number of patients with iliac
      vein stent thrombosis was 1. Twenty-one (12.1%) patients stated they had no
      improvement after both procedures. Correlating these group factors with the group
      of patients who improved their swelling after the combined procedures we found
      the following: 17 (81%) of these patients were females ( P=0.16). The average age
      was 68.4 (+/-17 SD) years ( P=0.72 SD). The average pain score was 3.2 (+/-3.7
      SD) ( P=0.68). The average degree of iliac vein stenosis was 60.2% (+/-15.9 SD) (
      P=0.02). Around 52.4% were Caucasians, 19% were African Americans, and 28.6% were
      Hispanics ( P=0.88). The number of patients with iliac vein stent thrombosis was
      1 ( P = 0.1). Conclusion These data suggest that the clinical factors including
      race are not clinically significant factors in the response to swelling after
      combined iliac stent and endovenous ablation procedures. Interestingly, a higher
      degree of iliac vein stenosis was associated with improved resolution of
      swelling.

PMID- 29473449
TI  - Aspirin use is associated with decreased radiologically-determined thrombus sac
      volume in abdominal aortic aneurysms.
AB  - Introduction Formation and renewal of intramural thrombus is associated with
      inflammation, and contributes to the complexity of aneurysm repair. Current
      cardiovascular pharmacotherapy includes several inflammatory modulators such as
      aspirin, statins, clopidogrel, and angiotensin-converting enzyme inhibitors. The
      purpose of our study was to investigate the effect of these inflammatory
      modulators on radiographically-determined thrombus sac volume. Methods Pre
      operative computed tomography scans were reviewed in patients who underwent
      elective infrarenal aortic aneurysm repair. Thrombus sac volume was obtained
      using a Hounsfield unit restricted region growth algorithm. Co-morbid conditions
      such as diabetes mellitus and post-operative complications were evaluated
      compared to thrombus sac volume. Receiver-operator characteristic curves were
      generated for thrombus sac volume and patients on the various cardiovascular
      pharmacotherapies. Results A total of 266 patients (mean age = 72.6 +/- 0.6
      years; mean thrombus sac volume = 58.7 (34.4-89.0) cm3) were identified.
      Acetylsalicylic acid use was associated with a decreased thrombus sac volume <=50
      cm3 (AUC = 0.616, p = 0.013) whereas statins ( p = 0.26), angiotensin-converting
      enzyme inhibitors ( p = 0.46), and clopidogrel ( p = 0.62) had no correlation to
      thrombus sac volume. Diabetes mellitus was not associated with thrombus sac
      volume ( p = 0.31). Conclusion Acetylsalicylic acid use is associated with
      decreased thrombus sac volume in a patient population undergoing elective
      abdominal aortic aneurysms repair. The effect of acetylsalicylic acid over other
      anti-inflammatory and anti-platelet agents is possibly attributable to its
      distinct mechanism of cyclooxygenase-1 inhibition. Diabetes mellitus, a known
      correlate of aneurysm incidence, is not associated with thrombus burden. The
      potential to alter aneurysm thrombus volume, thereby affecting aneurysm
      morphology, may yield a more favorable aneurysmal repair.

PMID- 29473450
TI  - Factor Structure of the Beliefs About Language Learning Inventory for Thai
      Students Learning Japanese.
AB  - The theoretical five-factor model for the 35-item Beliefs About Language Learning
      Inventory (BALLI) has rarely been examined empirically, despite its wide use to
      investigate language learning beliefs. This study examined the BALLI's
      dimensional structure with a sample of undergraduate students at a Thai
      university ( N = 537; male 43.4%, female 56.4%; age mean = 19.12 years), taking
      an elementary-level Japanese language course. Confirmatory factor analysis by M
      plus did not support Horwitz's theoretical model. While a five-factor model was
      identified from exploratory factor analysis, the combined items within each
      dimension were different from Horwitz's model. Thus, the original five-factor
      BALLI model was only partially supported. We were able to affirm the core aspects
      of language learning beliefs composed of eight BALLI items, and we offer a
      roadmap to develop the model.

PMID- 29473451
TI  - A nationwide cross-sectional survey of pharmacy students on pharmacogenetic
      testing in The Netherlands.
AB  - AIM: To benchmark knowledge and attitude of pharmacy students toward
      pharmacogenetics (PGx) and PGx testing and compare the results with practicing
      colleagues. METHODS: All pharmacy students in The Netherlands were invited to
      participate in a web-based survey consisting of 28 questions. Out of the 824
      invited students, 148 individuals (18.0%) completed the questionnaire. All
      responders believed in the concept of PGx and had high expectations toward PGx.
      The majority (96.6%) had received some form of education on PGx, but only 12.8%
      felt adequately informed. RESULTS: When compared with practicing pharmacists,
      differences were observed in the use of information and feeling qualified to
      recommend PGx testing. CONCLUSION: More education on PGx is required in the
      curriculum to fill the perceived knowledge gap among future pharmacists.

PMID- 29473452
TI  - A New Surgical Device for Anterograde Intraoperative Rectal Washout.
AB  - BACKGROUND: Colorectal cancer is the fourth most diffuse cause of death in the
      world and local recurrence is associated with a reduced long-term life
      expectancy, with a reduced quality of life. Rectal washout at the anastomosis
      site leads to a statistically significant reduction of local recurrences.
      METHODS: We developed the idea of a new laparoscopic stapler with an integrated
      washout system that could decontaminate the rectal stump before resection,
      without the need to enlarge the standard surgical incision or even to distort the
      incision site, closing the rectal stump just below the inferior part of the
      cancer, and then proceeding with the resection and stapling of the distal part of
      the tumor. Combined with these canonical functionalities, the new device,
      equipped with a patented washout system (patent number EP 3103401A1) will also
      allow to inject in the closed bowel a physiologic saline liquid. RESULTS: In
      force of the mechanical action of the liquid injected, carcinogenic exfoliated
      cells eventually floating in the affected region of the colonic lumen will be
      expelled through the anal orifice. The intraoperative rectal washout, both in
      minimally invasive and in traditional open surgery, thus becomes a simple,
      effective, and reproducible procedure. CONCLUSIONS: We describe the technical
      features and the possible clinical applications of a potentially new surgical
      laparoscopic stapler coupled with an integrated irrigation system. We have
      patented the system and we are developing a prototype with the aim to start an
      experimental pilot study.

PMID- 29473453
TI  - Wilhelm Fabricius von Hilden (1560-1634): The Pioneer of German Surgery.
AB  - Wilhelm Fabricius von Hilden (1560-1634) or also known with his Latinized name
      Guilielmus Fabricius Hildanus is considered the founder of scientific German
      surgery. He introduced new surgical techniques and invented new surgical
      instruments for the surgical treatment of nasal polyps, stone bladder, breast and
      ocular cancer, hydrocele, and ascites, while very ingenious were his amputation
      techniques. His most important surgical treatise was Observationem et curationem
      chirurgicam centuriae sex ( Six Hundred Surgical Observations and Treatments)
      first published in 1606.

PMID- 29473454
TI  - Correction of radiographic measurements of acetabular cup wear for variations in
      pelvis orientation.
AB  - Radiographic measurement of two-dimensional acetabular cup wear is usually
      carried out on a series of follow-up radiographs of the patient's pelvis. Since
      the orientation of the pelvis might not be consistent at every X-ray examination,
      the resulting change in view of the wear plane introduces error into the linear
      wear measurement. This effect is amplified on some designs of cup in which the
      centre of the socket is several millimetres below the centre of the cup or
      circular wire marker. This study describes the formulation of a mathematical
      method to correct radiographic wear measurements for changes in pelvis
      orientation. A mathematical simulation of changes in cup orientation and wear
      vectors caused by pelvic tilt was used to confirm that the formulae corrected the
      wear exactly if the radiographic plane of the reference radiograph was parallel
      to the true plane of wear. An error analysis showed that even when the true wear
      plane was not parallel to the reference radiographic plane, the formulae could
      still provide a useful correction. A published correction formula was found to be
      ineffective.

PMID- 29473455
TI  - Sagittal flexion arc evaluation for a modern generation single-radius femoral
      component design.
AB  - Single-radius femoral total knee design aims to deliver improved kinematic
      behaviour when compared to the standard two-radii geometry. This study has
      evaluated the behaviour, through a functional range of motion in the sagittal
      plane, of a single-radius femoral component compared to a dual-radius standard
      knee construct. Particular focus was placed on how the flexion axes of the native
      and replaced knee approximated to the transepicondylar axis through a loaded
      navigated knee design. Significant differences in flexion arcs were noted between
      the native and total knee arthroplasty state. These arcs were not uniform in all
      knees and did not display single-radius behaviour. There were no significant
      differences in the location of flexion axes in the native and total knee
      arthroplasty knee. Both exhibited similar posterior and inferior transverse axes
      of motion with respect to the anatomical epicondylar axis. This work has cast
      doubt on the reliability under loaded conditions of the single-radius concept,
      but the close proximity of the flexion axes of each replaced knee in relation to
      the functional flexion axis of the native knee may be the true basis of this
      purported improved kinematic performance.

PMID- 29473456
TI  - Peripheral somatosensory stimulation and postural recovery after stroke - a
      systematic review.
AB  - Purpose It is hypothesized that peripheral somatosensory stimulation (PSS) can
      promote postural recovery after stroke by increasing afferent input and postural
      contribution of the paretic leg. Therefore, this systematic review aims to
      investigate which PSS approaches are documented and investigated on
      effectiveness. Methods Five databases (PubMed, Web of Science, PEDro, Cochrane
      Library Trials, RehabData) have been searched on clinical studies in stroke
      rehabilitation, investigating PSS, which is defined as a non-motor and focal
      stimulation to the paretic leg aiming an increase in somatosensory input. Results
      Twenty studies present different PSS approaches (mainly electrical and vibration
      stimulation) and following results: (I) There is an immediate effect after a
      single session of PSS on postural stability. In contrast, (II) repetitive
      sessions of isolated PSS led to highly inconsistent results. Finally, (III) PSS
      as an adjuvant to exercises did promote long-term postural recovery. Conclusion
      PSS is found to be effective immediately and on a long-term as an adjuvant
      therapy only in improving postural stability in a chronic stroke population.
      However, if PSS enhances paretic leg postural contribution remains unclear.
      Future research is warranted considering promising results and high prevalence of
      postural instability impacting daily life of stroke survivors.

PMID- 29473458
TI  - Hyperbaric oxygen as an adjuvant to temozolomide nanoparticle inhibits glioma
      growth by inducing G2/M phase arrest.
AB  - AIM: To study the effects of combinational treatment of hyperbaric oxygen (HBO)
      and nanotemozolomide in glioma. MATERIALS & METHODS: Temozolomide (TMZ)-loaded
      porous silicon nanoparticles (TMZ/PSi NPs) were prepared. In vitro and in vivo
      evaluations were performed. RESULTS: The cell uptake of TMZ/PSi NPs could be
      tracked by autofluorescence of porous silicon. The concentration of oxygen in
      tumor was improved and the antitumor rate was increased to 84.2% in the TMZ/PSi
      NPs combined with HBO group. The viability of hypoxia-induced glioma C6 cells was
      decreased and cell cycle was arrested at G2/M phase in response to TMZ/PSi NPs
      treatment with HBO compared with continuous treatment with hypoxia. CONCLUSION:
      The combinational treatment of TMZ/PSi NPs and HBO could be a promising
      therapeutic strategy for glioma.

PMID- 29473459
TI  - Safety I-II, resilience and antifragility engineering: a debate explained through
      an accident occurring on a mobile elevating work platform.
AB  - Occupational health and safety (OHS) represents an important field of exploration
      for the research community: in spite of the growth of technological innovations,
      the increasing complexity of systems involves critical issues in terms of
      degradation of the safety levels. In such a situation, new safety management
      approaches are now mandatory in order to face the safety implications of the
      current technological evolutions. Along these lines, performing risk-based
      analysis alone seems not to be enough anymore. The evaluation of robustness,
      antifragility and resilience of a socio-technical system is now indispensable in
      order to face unforeseen events. This article will briefly introduce the topics
      of Safety I and Safety II, resilience engineering and antifragility engineering,
      explaining correlations, overlapping aspects and synergies. Secondly, the article
      will discuss the applications of those paradigms to a real accident, highlighting
      how they can challenge, stimulate and inspire research for improving OHS
      conditions.

PMID- 29473457
TI  - An ecoimmunological approach to study evolutionary and ancient links between
      coagulation, complement and Innate immunity.
AB  - Coagulation, complement, and innate immunity are tightly interwoven and form an
      alliance that can be traced back to early eukaryotic evolution. Here we employed
      an ecoimmunological approach using Tissue Factor Pathway Inhibitor (TFPI)-1
      derived peptides from the different classes of vertebrates (i.e. fish, reptile,
      bird, and mammals) and tested whether they can boost killing of various human
      bacterial pathogens in plasma. We found signs of species-specific conservation
      and diversification during evolution in these peptides that significantly impact
      their antibacterial activity. Though all peptides tested executed bactericidal
      activity in mammalian plasma (with the exception of rodents), no killing was
      observed in plasma from birds, reptiles, and fish, pointing to a crucial role for
      the classical pathway of the complement system. We also observed an interference
      of these peptides with the human intrinsic pathway of coagulation though, unlike
      complement activation, this mechanism appears not to be evolutionary conserved.

PMID- 29473460
TI  - Global frameworks, local strategies: Women's rights, health, and the tobacco
      control movement in Argentina.
AB  - The article examines how civil society organisations in Argentina used the United
      Nations Convention on the Elimination of All Forms of Discrimination Against
      Women (CEDAW) to frame the country's failure to enact strong national tobacco
      control legislation as a violation of women's rights in the late 2000s. We
      analyze this case study through the politics of scale, namely the social
      processes that produce, reproduce, and contest the boundaries of policies and
      socio-economic relations. This approach understands how multiple scales overlap
      and connect to obstruct or enhance the right to health in Latin America. In
      Argentina, the global organisation of tobacco companies, the reach of
      international financial institutions and the national dynamics of economic
      austerity and export-orientation promoted the local production and use of tobacco
      (leaf and cigarettes) and reproduced health inequalities in the country
      throughout the 1990s and the early 2000s. Yet, the visible legacy of local and
      national human rights struggles in the adoption of international human rights
      treaties into Argentina's national constitution allowed the tobacco control
      movement to link the scale of women's bodies to the right to health through the
      use of CEDAW to change national legislation, tackling the social determinants of
      the tobacco epidemic.

PMID- 29473461
TI  - Primary aldosteronism and thyroid disorders in atrial fibrillation: A Swedish
      nationwide case-control study.
AB  - Background Atrial fibrillation is associated with hyperthyroidism. Patients with
      primary aldosteronism have an increased prevalence of atrial fibrillation.
      However, the prevalence of primary aldosteronism in the atrial fibrillation
      population is unknown. Aim This nationwide case-control study aimed to compare
      the prevalence of primary aldosteronism and thyroid disorders in patients with
      atrial fibrillation with that of age- and sex-matched controls. Methods We
      identified all atrial fibrillation cases in Sweden between 1987 and 2013 ( n =
      713,569) by using the Swedish National Patient Register. A control cohort without
      atrial fibrillation was randomly selected from the Swedish Total Population
      Register with a case to control ratio of 1:2. This control cohort was matched for
      age, sex and place of birth ( n = 1,393,953). Results The prevalence of primary
      aldosteronism in December 2013 was 0.056% in the atrial fibrillation cohort and
      0.024% in controls. At the same time, the prevalence of hypothyroidism was 5.9%
      in the atrial fibrillation cohort and 3.7% in controls. The prevalence of
      hyperthyroidism was 2.3% in the atrial fibrillation cohort and 0.8% in controls.
      Conclusion This study shows, for the first time, a doubled prevalence of primary
      aldosteronism in a large cohort of patients with atrial fibrillation compared
      with the general population. There is also an increased prevalence of hypo- and
      hyper-thyroidism in patients with atrial fibrillation compared with the general
      population.

PMID- 29473462
TI  - Association of serum potassium concentration with mortality and ventricular
      arrhythmias in patients with acute myocardial infarction: A systematic review and
      meta-analysis.
AB  - Background Challenging clinical practice guidelines that recommend serum
      potassium concentration between 4.0-5.0 mEq/L or >=4.5 mEq/L in patients with
      acute myocardial infarction, recent studies found increased mortality risks in
      patients with a serum potassium concentration of >=4.5 mEq/L. Studies
      investigating consequences of hypokalemia after acute myocardial infarction
      revealed conflicting results. Therefore, the aim of this systematic review and
      meta-analysis was to combine evidence from previous studies on the association of
      serum potassium concentration with both short and long-term mortality as well as
      the occurrence of ventricular arrhythmias. Design Systematic review and meta
      analysis. Methods A structured search of MEDLINE and EMBASE databases yielded 23
      articles published between 1990 and January 2017 that met the inclusion criteria.
      Study selection, data extraction and quality assessment were carried out by three
      reviewers. Random effects models were used to pool estimates across the included
      studies and sensitivity analyses were performed when possible. Results Twelve
      studies were included in the meta-analysis. Both pooled results from six studies
      investigating short-term mortality and from five studies examining long-term
      mortality revealed significantly increased risks in patients with serum potassium
      concentrations of <3.5 mEq/L, 4.5-<5.0 mEq/L and >=5.0 mEq/L after acute
      myocardial infarction. In addition, a serum potassium concentration of <3.5 mEq/L
      was significantly associated with the occurrence of ventricular arrhythmias.
      Conclusions Mortality, both short and long term, and the occurrence of
      ventricular arrhythmias in patients with acute myocardial infarction seem to be
      negatively associated with hypokalemic serum potassium concentration. There is
      evidence for adverse consequences of serum potassium concentrations of >=4.5
      mEq/L. Due to the heterogeneity among existing studies, further research is
      necessary to confirm the need to change clinical practice guidelines.

PMID- 29473463
TI  - Markers of neutrophil extracellular traps are associated with adverse clinical
      outcome in stable coronary artery disease.
AB  - Background Neutrophil extracellular traps, comprising chromatin and granule
      proteins, have been implicated in atherothrombosis. Design and methods We
      investigated whether the circulating neutrophil extracellular traps markers,
      double-stranded DNA and myeloperoxidase-DNA were associated with clinical outcome
      and hypercoagulability in patients with stable coronary artery disease. Patients
      with angiographically verified stable coronary artery disease ( n = 1001) were
      included. Follow-up was 2 years, recording 106 clinical endpoints (unstable
      angina, non-haemorrhagic stroke, myocardial infarction or death). Serum collected
      at baseline was used to determine double-stranded DNA and myeloperoxidase-DNA
      levels. Results The neutrophil extracellular traps markers were weakly
      intercorrelated ( r = 0.103, P = 0.001). Patients with the highest quartile of
      double-stranded DNA had weakly but significantly elevated hypercoagulability
      markers (prothrombin fragment 1+2, D-dimer, free and total tissue factor pathway
      inhibitor ( P < 0.001 for all)). Men, smokers, patients with metabolic syndrome
      and patients with a previous myocardial infarction had significantly elevated
      double-stranded DNA levels ( P <= 0.002 for all). Significantly higher double
      stranded DNA levels were observed in the group experiencing a clinical endpoint
      compared to the group without ( P = 0.019). When categorising double-stranded DNA
      into quartiles, a distinct cut-off between the lowest and upper three quartiles
      was observed. Adjusting for relevant covariates, patients in the upper three
      quartiles had an odds ratio of 2.01 (95% confidence interval 1.12, 3.58, P =
      0.019) for experiencing a clinical endpoint. Myeloperoxidase-DNA was not
      significantly associated with clinical outcome or hypercoagulability. Conclusions
      Double-stranded DNA levels were significantly related to adverse clinical outcome
      after 2 years, but only weakly associated with hypercoagulability. These
      observations suggest that the detrimental effects of neutrophil extracellular
      traps in coronary artery disease might extend beyond those related to
      hypercoagulability.

PMID- 29473464
TI  - Association between serum calcium, serum phosphate and aortic stenosis with
      implications for prevention.

PMID- 29473466
TI  - Editorial.

PMID- 29473467
TI  - Checkpoint inhibitors: 'raising the bar' also in brain metastases from non-small
      cell lung cancer?
AB  - Despite efforts, brain metastases (BM) remain a critical issue in the management
      of patients affected by non-small-cell lung cancer (NSCLC). To date, radiotherapy
      is still considered the gold standard treatment; on the other hand, systemic
      chemotherapeutical agents are not so often an effective therapy for BM, whereas
      targeted agents in oncogene-addicted disease have shown a good activity also on
      BM. Anti-programmed death-1/programmed death ligand-1 agents represent a new
      valid therapeutic strategy for NSCLC as well as for several tumor types, but
      their efficacy on patients with BM is still unclear mainly due to the strict
      selection criteria adopted in clinical trials. The aim of the present article is
      to discuss the potential activity of checkpoint inhibitors in patients with BM
      from NSCLC.

PMID- 29473468
TI  - Is it possible to rechallenge with PD-1/PD-L1 inhibitors after progression?

PMID- 29473469
TI  - Immunotherapy for thoracic oncology gone viral.
AB  - Immune therapy has now been incorporated into the standard of care for non-small
      cell lung cancer based on randomized trials showing superiority of anti-PD1
      antibodies compared with chemotherapy. Thus there is a renewed interest in immune
      approaches to treating lung cancer. One promising approach is with oncolytic
      viruses that either naturally or through engineering, preferentially infect or
      kill cancer cells. In preclinical models of different thoracic cancers, it has
      been found that these viruses can induce immune responses through multiple
      mechanisms. Thus, in addition to their direct cytolytic effects, oncolytic
      viruses can also promote antitumor immunity. This review will discuss the immune
      effects of oncolytic viruses lung cancers and the approaches that are underway to
      augment immune therapy in clinical testing.

PMID- 29473470
TI  - Tumor lysate particle loaded dendritic cell vaccine: preclinical testing of a
      novel personalized cancer vaccine.
AB  - AIM:  We developed a novel approach to efficiently deliver autologous tumor
      antigens to the cytoplasm of dendritic cells (DC) using yeast cell wall particles
      (YCWP). MATERIALS AND METHODS:  Loading of YCWP, leakage of protein from loaded
      YCWP and cytoplasmic delivery of YCWP content was assessed using fluorescent
      tagged experiments. Spectrophotometric analysis compared the epitope-specific T
      cell responses following antigen presentation via YCWP versus exogenous loading.
      The in vivo effectiveness of tumor lysate (TL) particle loaded DC (TLPLDC)
      vaccine was assessed using murine melanoma models. RESULTS: In fluorescence
      tagged experiments, YCWP efficiently delivered antigen to the cytoplasm of DC.
      TLPLDC loading was more effective than conventional exogenous loading of DC.
      Finally, in murine melanoma models, TLPLDC outperformed an analogous dendritoma
      vaccine. CONCLUSION: The TLPLDC vaccine is commercially scalable and holds the
      potential of producing personalized vaccines.

PMID- 29473471
TI  - Malignant mesothelioma clinical trial combines immunotherapy drugs.
AB  - Immunotherapy by checkpoint inhibitor is effective for a number of solid tumors
      including malignant mesothelioma. Studies utilizing single-agent PD-1 or PD-L1
      inhibitor for mesothelioma have reported tumor response rates in approximately 10
      20% of patients treated. Given the success of combining these agents with CTLA-4
      inhibitor in melanoma, there is a strong rationale to study it in mesothelioma.
      Recently results from clinical trials investigating this approach have been
      released. Though limited by small sample size, the studies conclusively
      demonstrated feasibility and suggested a modestly higher tumor response rate than
      one would expect from treatment with single-agent PD-1 or PD-L1 inhibitor.
      Nevertheless, toxicity was also increased. Immunotherapy-related deaths due to
      encephalitis, renal failure and hepatitis were observed. Further studies are
      warranted.

PMID- 29473472
TI  - Application of cancer-testis antigens in immunotherapy of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a worldwide common malignancy with poor
      prognosis. Several studies have aimed at identification of appropriate biomarkers
      for early detection of this cancer. Cancer-testis antigens (CTAs) as a novel
      group of tumor-associated antigens have been demonstrated to be expressed in HCC
      samples as well as peripheral blood samples from these patients but not in the
      corresponding adjacent noncancerous samples. Such pattern of expression has
      provided them an opportunity to be used as immunotherapeutic targets. The
      detection of spontaneous immune responses against CTAs in HCC patients has
      prompted design of CTA-based immunotherapeutic protocols in these patients. The
      results of some clinical trials have been promising in a subset of patients.

PMID- 29473473
TI  - Crisis of Meaning Predicts Suicidality in Youth Independently of Depression.
AB  - BACKGROUND: At times, the question for meaning comes to nothing and a crisis of
      meaning ensues. This state is very painful, but difficult to account. Both those
      who suffer from it and care professionals find themselves at a loss for words.
      AIMS: This study introduces an operationalization of a crisis of meaning. It aims
      to distinguish the concept from depression, and to investigate whether a crisis
      of meaning can explain suicidality beyond the known protective and risk factors
      self-esteem, family functioning, life-event load, and depression. METHOD: Final
      year school pupils in Ecuador (N = 300) completed questionnaires assessing the
      above variables. Data were analyzed using chi-square, hierarchic multiple
      regression, serial mediation, and moderator analyses. RESULTS: Crisis of meaning
      was distinguished from depression. It explained a significant amount of variance
      in suicidality beyond the mentioned protective and risk factors. For males,
      crisis of meaning was the only significant risk factor, and the strongest
      predictor overall. The acute risk factors depression and crisis of meaning
      mediated the effects of the baseline factors self-esteem, family functioning, and
      life-event load on suicidality. LIMITATIONS: The study was cross-sectional;
      assessed factors predicted variance in suicidal thoughts, plans, and past suicide
      attempts, while their relevance cannot be generalized to actual future suicide
      attempts. CONCLUSION: A crisis of meaning is an important factor to take into
      account in further research on the prevention and treatment of people at risk of
      suicide.

PMID- 29473475
TI  - Clinical Profiles Among Greek Adolescent Suicide Attempters.
AB  - BACKGROUND: Suicide attempts are a significant public health problem among youth,
      resulting in a major social and economic burden for communities and a devastating
      impact on families. AIMS: To determine whether we can identify distinct clinical
      profiles using latent class analysis in a clinical sample of Greek adolescents
      who were admitted to hospital following a suicide attempt. METHOD: Data on 11
      clinical parameters from 182 adolescents were analyzed, with a two-class solution
      selected as the best fitting among the one- through three-class solutions that
      were examined. RESULTS: We observed two distinct classes, specifically in the
      probability of mood disorders, substance use disorders, abandonment/neglect, and
      displaying traits of personality disorders. While most of the adolescents who
      attempted suicide showed a low probability of these parameters (71.7%), about a
      third of the sample (28.3%) showed a much more severe clinical profile. Analyses
      of pertinent contextual and risk factors indicated that those with a more severe
      clinical profile tend to come from overall more dysfunctional family systems,
      have more problems in school, and have made a previous attempt. CONCLUSION: We
      conclude that the adolescent suicide attempt population is a heterogeneous group
      in need of focused differentiated care specifically targeted to particular
      subgroups.

PMID- 29473476
TI  - Challenges of Combining Perspectives.
AB  - BACKGROUND: Asylum seekers have increased risk of suicide and suicidal behavior,
      with differences related to origin, gender, and age. There are barriers to
      communication in clinical encounters between asylum seekers and clinicians. There
      is insufficient knowledge about how communication in the clinical encounter
      affects the suicide risk in female asylum seekers. AIMS: To explore the
      documented communication between female asylum-seeking suicide attempters and
      clinicians and how it affects treatment. METHOD: The medical records of 18 asylum
      seeking women who had attempted suicide were analyzed with content analysis.
      RESULTS: Communication between patients and clinicians was affected by: the
      unbearable realities of the women; difficulties for clinicians in decoding
      languages of distress, and understanding trauma and subjective meanings of
      suicide; challenges of combining patients' and clinicians' perspectives; and a
      sense of shared powerlessness. LIMITATIONS: The medical records did not give
      direct access to the patient's experience, only to the patient as documented by
      the clinician. CONCLUSION: The results suggest that clinicians working with
      asylum seekers who have attempted suicide need to develop an understanding of
      social and cultural factors and of trauma issues. A question for further study is
      how an enhanced integration of context and subjectivity in psychiatric practice
      would equip clinicians for the specific challenges encountered.

PMID- 29473479
TI  - Distinguishing statistical and clinical significance in meta-analysis (Comment on
      "The effectiveness of hydrokinesiotherapy on postural balance of hemiplegic
      patients after stroke: a systematic review and meta-analysis" by Iatridou G. et
      al.).

PMID- 29473478
TI  - Helicobacter pylori SabA binding gangliosides of human stomach.
AB  - Adhesion of Helicobacter pylori to the gastric mucosa is a prerequisite for the
      pathogenesis of H. pylori related diseases. In this study, we investigated the
      ganglioside composition of human stomach as the target for attachment mediated by
      H. pylori SabA (sialic acid binding adhesin). Acid glycosphingolipids were
      isolated from human stomach and separated into subfractions, which were
      characterized by mass spectrometry and by binding of antibodies, bacteria, and
      Solanum tuberosum lectin. H. pylori SabA binding gangliosides were characterized
      as Neu5Acalpha3-neolactohexaosylceramide and Neu5Acalpha3
      neolactooctaosylceramide, while the other acid human stomach glycosphingolipids
      characterized (sulfatide and the gangliosides GM3, GD3, GM1, Neu5Acalpha3
      neolactotetraosylceramide, GD1a and GD1b) were not recognized by the bacteria.
      Defining H. pylori binding glycosphingolipids of the human gastric mucosa will be
      useful to specifically target this microbe-host interaction for therapeutic
      intervention.

PMID- 29473480
TI  - Dual-task training effects on motor and cognitive functional abilities in
      individuals with stroke: a systematic review.
AB  - OBJECTIVE: This systematic review aimed to examine the effects of dual-task
      balance and mobility training in people with stroke. METHODS: An extensive
      electronic databases literature search was conducted using MEDLINE, PubMed,
      EBSCO, The Cochrane Library, Web of Science, SCOPUS, and Wiley Online Library.
      Randomized controlled studies that assessed the effects of dual-task training in
      stroke patients were included for the review (last search in December 2017). The
      methodological quality was evaluated using the Cochrane Collaboration
      recommendation, and level of evidence was determined according to the criteria
      described by the Oxford Center for Evidence-Based Medicine. RESULTS: About 13
      articles involving 457 participants were included in this systematic review. All
      had substantial risk of bias and thus provided level IIb evidence only. Dual-task
      mobility training was found to induce more improvement in single-task walking
      function (standardized effect size = 0.14-2.24), when compared with single-task
      mobility training. Its effect on dual-task walking function was not consistent.
      Cognitive-motor balance training was effective in improving single-task balance
      function (standardized effect size = 0.27-1.82), but its effect on dual-task
      balance ability was not studied. The beneficial effect of dual-task training on
      cognitive function was provided by one study only and thus inconclusive.
      CONCLUSION: There is some evidence that dual-task training can improve single
      task walking and balance function in individuals with stroke. However, any firm
      recommendation cannot be made due to the weak methodology of the studies
      reviewed.

PMID- 29473481
TI  - Early self-managed focal sensorimotor rehabilitative training enhances functional
      mobility and sensorimotor function in patients following total knee replacement:
      a controlled clinical trial.
AB  - OBJECTIVE: To assess the effects of early self-managed focal sensorimotor
      training compared to functional exercise training after total knee replacement on
      functional mobility and sensorimotor function. DESIGN: A single-blind controlled
      clinical trial. SETTING: University Hospital of Rion, Greece. SUBJECTS: A total
      of 52 participants following total knee replacement. OUTCOME MEASURES: The
      primary outcome was the Timed Up and Go Test and the secondary outcomes were
      balance, joint position error, the Knee Outcome Survey Activities of Daily Living
      Scale, and pain. Patients were assessed on three separate occasions (presurgery,
      8 weeks post surgery, and 14 weeks post surgery). INTERVENTION: Participants were
      randomized to either focal sensorimotor exercise training (experimental group) or
      functional exercise training (control group). Both groups received a 12-week home
      based programme prescribed for 3-5 sessions/week (35-45 minutes). RESULTS:
      Consistently greater improvements ( F2,98 = 4.3 to 24.8; P < 0.05) in group mean
      scores favour the experimental group compared to the control group: Timed Up and
      Go (7.8 +/- 2.9 seconds vs. 4.6 +/- 2.6 seconds); balance (2.1 +/- 0.9 degrees 
      vs. 0.7 +/- 1.2 degrees ); joint position error (13.8 +/- 7.3 degrees  vs. 6.2 +/
      9.1 degrees ); Knee Outcome Survey Activities of Daily Living Scale (44.2 +/-
      11.3 vs. 26.1 +/- 11.4); and pain (5.9 +/- 1.3 cm vs. 4.6 +/- 1.1 cm). Patterns
      of improvement for the experimental group over time were represented by a
      relative effect size range of 1.3-6.5. CONCLUSIONS: Overall, the magnitude of
      improvements in functional mobility and sensorimotor function endorses using
      focal sensorimotor training as an effective mode of rehabilitation following knee
      replacement.

PMID- 29473482
TI  - Prospective surveillance and targeted physiotherapy for arm morbidity after
      breast cancer surgery: a pilot randomized controlled trial.
AB  - OBJECTIVE: To evaluate prospective surveillance and targeted physiotherapy (PSTP)
      compared to education (EDU) on the prevalence of arm morbidity and describe the
      associated program cost. DESIGN: Pilot randomized single-blinded controlled
      trial. SETTING: Urban with assessments and treatment delivered in hospitals.
      PARTICIPANTS: Women scheduled for breast cancer surgery. INTERVENTIONS:
      Participants were randomly assigned (1:1) to PSTP ( n = 21) or EDU ( n = 20) and
      assessed presurgery and 12 months postsurgery. All participants received usual
      care, namely, preoperative education and provision of an education booklet with
      postsurgical exercises. The PSTP group was monitored for arm morbidity every
      three months and referred for physiotherapy if arm morbidity was identified. The
      EDU group received three education sessions on nutrition, stress and fatigue
      management. MAIN OUTCOME MEASURES: Arm morbidity was based on changes in the
      surgical arm(s) from presurgery in four domains: (1) shoulder range of motion,
      (2) strength, (3) volume, and (4) upper body function. Complex arm morbidity
      indicated >=2 domains impaired. Second, the cost of the PSTP program was
      described. RESULTS: At 12 months, 18 (49%) participants (10 PSTP and 8 EDU) had
      arm morbidity, with EDU participants presenting more complex arm morbidity
      compared to PSTP participants. PSTP participants attended 4.4 of 5 assessments
      with 90% retention. The PSTP program cost was $150 covered by the Health Care
      Provider and the Patient Out-of-Pocket Travel cost was CAN$40. CONCLUSION: Our
      results suggest that PSTP is feasible among women with breast cancer for early
      identification of arm morbidity. A larger study is needed to determine the cost
      and effectiveness benefits.

PMID- 29473483
TI  - Patient Perceptions of Text Messaging to Improve Antiretroviral Therapy
      Adherence: A Qualitative Study of Patients in a Ryan White Clinic.
AB  - Evidence on the use of short message service (SMS) to improve medication
      adherence in people living with HIV (PLHIV) is mounting, yet qualitative research
      on patient perceptions regarding SMS content and utility for HIV/AIDS remains
      nascent. To explore the experience of receiving medication reminders via SMS
      among PLHIV, 45 uninsured and underinsured PLHIV nested within the intervention
      arm of a larger study received daily, 1-way SMS adherence reminders. Qualitative
      data were collected by face-to-face, structured interview and were analyzed using
      conventional content analysis methods. Three main themes emerged from the data:
      (1) reminders helping with adherence, (2) concerns about delivery modes, and (3)
      the need for confidentiality. Study findings offer enhanced focus on an emerging
      strategy in patient-centered HIV care: Equipped with greater context on the
      experiences of PLHIV using SMS adherence reminders, health-care providers can
      offer more targeted support and thereby maximize the benefits of this popular and
      powerful technology.

PMID- 29473484
TI  - HIV-Positive Patients' Perceptions of Antiretroviral Therapy Adherence in
      Relation to Subjective Time: Imprinting, Domino Effects, and Future Shadowing.
AB  - Antiretroviral treatment adherence barriers are major concerns in HIV care. They
      are multiple and change over time. Considering temporality in patients'
      perceptions of adherence barriers could improve adherence management. We explored
      how temporality manifests itself in patients' perceptions of adherence barriers.
      We conducted 2 semi-structured focus groups on adherence barriers with 12 adults
      with HIV which were analyzed with grounded theory. A third focus group served to
      validate the results obtained. Three temporal categories were manifest in HIV
      positive patients' perceptions of barriers: (1) imprinting (events with lasting
      impacts on patients), (2) domino effects (chain of life events), and (3) future
      shadowing (apprehension about long-term adherence). An overarching theme,
      weathering (gradual erosion of abilities to adhere), traversed these categories.
      These temporalities explain how similar barriers may be perceived differently by
      patients. They could be useful to providers for adapting their interventions and
      improving understanding of patients' subjective experience of adherence.

PMID- 29473485
TI  - High Virologic Failure Rates with Maraviroc-Based Salvage Regimens Among Indian
      Patients: A Preliminary Analysis-Maraviroc Effectiveness in HIV-1 Subtype C.
AB  - BACKGROUND: There is no information on the clinical effectiveness of Maraviroc
      (MVC) amongst People Living with HIV (PLHIV) in India infected with HIV-1 Subtype
      C viruses. METHODS: We conducted a retrospective chart review of adult PLHIV on
      MVC based Antiretroviral (ARV) regimens for at least 6 months. Maraviroc was
      initiated amongst PLHIV with documented R5 tropic viruses (determined by in-house
      population sequencing of the V3 loop in triplicate and interpreted using the
      Geno2Pheno algorithm) in combination with an Optimized Background regimen
      (designed using genotypic resistance testing and past ARV history). Plasma viral
      loads (PVL) are performed 6 months post-initiation and annually thereafter.
      Primary outcome d. Median duration on MVC treatment was 1.8 years (range 1-2.9
      years) while median duration of ART prior to switching to MVC was 13 years.
      Maraviroc was combined with Darunavir/ritonavir (DRV/r) (n=10), Atazanavir/r
      (ATV/r) (n=2) and Lopinavir/r (LPV/r) (n=1). All PLHIV were infected with HIV-1
      Subtype C. Only 23.3% PLHIV achieved virologic suppression at 6 months and
      sustained it for 2.3 years. Median CD4 count change from baseline was +117
      (n=13), +228 (n=10), +253 (n=9), and +331 (n=4) at 6, 12, 18 and 24 months
      respectively. Repeat tropism among patients with virologic failure demonstrated
      R5 virus. CONCLUSIONS: High rates of virologic failure was seen when MVC was used
      amongst treatment experienced PLHIV infected with HIV-1 Subtype C in India. was
      the proportion of PLHIV with virologic success (PVL<50 copies/ml) at last follow
      up visit. RESULTS: Data on 13 PLHIV were analyze.

PMID- 29473486
TI  - Striving for the best: WONCA global standards for continuing professional
      development for family doctors.
AB  - While all physicians must continue to learn new knowledge through their careers,
      their post-training continuing professional development (CPD) has received less
      attention. Problems include lack of support for physicians, frequent deviations
      from best practices such as mandatory participation, focus on community need, and
      clear conflicts of interest amongst providers. Additionally, specialists from
      other disciplines catering to different patient populations often provide CPD for
      family doctors. The Working Party on Education of the World Organisation of
      Family Doctors (WONCA) sought to develop global standards in CPD for family
      doctors. The standards were developed through an iterative process with reference
      to published best practices for effective CPD. Adapted for family doctors from
      the World Federation for Medical Education's CPD for Medical Doctors: WFME Global
      Standards for Quality Improvement', the WONCA CPD Standards for Family Doctors
      were approved by WONCA Council in November 2016. The objectives of the standards
      are to: (1) Provide a resource for family doctors and/or groups of family doctors
      to design and structure a program of CPD to reinforce lifelong learning; (2)
      Optimise current CPD systems such that, through more effective program design and
      delivery, family doctors are advancing in patient care and their discipline; (3)
      Offer a set of globally recognised standards developed through a family medicine
      perspective to provide feedback on existing CPD programs and systems and
      encourage international recognition of CPD activities. The WONCA Global CPD
      Standards should inspire best practices in family medicine CPD, assisting family
      doctors in providing excellent care.

PMID- 29473487
TI  - New design, development, and optimization of an in-house quantitative TaqMan Real
      time PCR assay for HIV-1 viral load measurement.
AB  - Background Viral load measurement is commonly applicable to monitor HIV infection
      in patients to determine the number of HIV-RNA in serum samples of individuals.
      The aim of the present study was to set up a highly specific, sensitive, and
      reproducible home-brewed Real-time PCR assay based on TaqMan chemistry to
      quantify HIV-1 RNA genome. Methods In this study, three sets of primer pairs and
      a TaqMan probe were designed for HIV subtypes conserved sequences. An internal
      control was included in this assay to evaluate the presence of inhibition.
      Standard curve and threshold cycle values were determined using in vitro
      transcribed RNA from int region of HIV-1. A serial dilution of RNA standards was
      generated by in vitro transcription, from 10 to 109 copies/ml to find the
      sensitivity and the limit of detection (LOD) of the assay and to evaluate its
      performance in a quantitative RT-PCR assay. Results The assay has a low LOD
      equivalent to 33.13 copies/ml of HIV-1 RNA and a linear range of detection from
      10 to 109 copies/ml. The coefficient of variation (CV) for Inter and Intra-assay
      precision of this in-house HIV Real-time RT-PCR ranged from 0.28 to 2.49% and
      0.72 to 4.47%, respectively. The analytical and clinical specificity was 100%.
      Conclusions The results indicate that the developed method has a suitable
      specificity and sensitivity and is highly reproducible and cost-benefit.
      Therefore, it will be useful to monitor HIV infection in plasma samples of
      individuals.

PMID- 29473489
TI  - Corrigendum.

PMID- 29473488
TI  - Breast cancer services in Vietnam: a scoping review.
AB  - BACKGROUND: Breast cancer incidence has been increasing consistently in Vietnam.
      Thus far, there have been no analytical reviews of research produced within this
      area. OBJECTIVES: We sought to analyse the nature andextent of empirical studies
      about breast cancer in Vietnam, identifying areas for future research and
      systemsstrengthening. METHODS: We undertook a scoping study using a five-stage
      framework to review published and grey literature in English and Vietnamese on
      breast cancer detection, diagnosis and treatment. We focused specifically on
      research discussing the health system and service provision. RESULTS: Our results
      show that breast cancer screening is limited, with no permanent or integrated
      national screening activities. There is a lack of information on screening
      processes and on the integration of screening services with other areas of the
      health system. Treatment is largely centralised, and across all services there is
      a lack of evaluation and data collection that would be informative for
      recommendations seeking to improve accessibility and quality of breast cancer
      services. CONCLUSIONS: This paper is the first scoping review of breast cancer
      services in Vietnam. It outlines areas for future focus for policy makers and
      researchers with the objective of strengthening service provision to women with
      breast cancer across the country while also providing a methodological example
      for how to conduct a collaborative scoping review.

PMID- 29473490
TI  - Identification and Analysis of Key Residues Involved in Folding and Binding of
      Protein-carbohydrate Complexes.
AB  - BACKGROUND: Protein-carbohydrate interactions play vital roles in several
      biological processes in living organisms. The comparative analysis of binding
      site residues along with stabilizing residues in protein-carbohydrate complexes
      provides ample insights to understand the structure, function and recognition
      mechanism. OBJECTIVE: The main objective of this study is to identify and analyze
      the residues, which are involved in both folding and binding of the protein
      carbohydrate complexes. METHODS: We have identified the stabilizing residues
      using the knowledge of hydrophobicity, longrange interactions and conservation,
      as well as binding site residues using a distance cutoff of 3.5A between any
      heavy atoms in protein and ligand. Residues, which are common in stabilizing and
      binding, are termed as key residues. These key resides are analyzed with various
      sequence and structure based parameters such as frequency of occurrence,
      surrounding hydrophobicity, longrange order and conservation score. RESULTS: In
      this work, we have identified 2.45% binding site residues in a non-redundant
      dataset of 1130 complexes using distance-based criteria and 7.07% stabilizing
      residues using the concepts of hydrophobicity, long-range interactions and
      conservation of residues. Further, 5.9% of binding and 2.04% of stabilizing
      residues are common to each other, which are termed as key residues. The key
      residues have been analysed based on protein classes, carbohydrate types, gene
      ontology functional classifications, amino acid preference and structure-based
      parameters. We found that all-beta, alpha+beta and alpha/beta have more key
      residues than other protein classes and most of the KRs are present in beta
      strands, which shows their importance in stability and binding of complexes. On
      the ligand side, Lsaccharide has the highest number of key residues and it has a
      high percentage of KRs in SRs and BRs than other carbohydrate types. Further,
      polar and charged residues have a high tendency to serve as key residues.
      Classifications based on gene ontology terms revealed that Lys is preferred in
      all the three groups: molecular functions, biological processes and cellular
      components. Key residues have 6 to 9 contacts within the protein and make only
      one contact with the carbohydrate ligand. These contacts are dominant to form
      polar-nonpolar contacts followed by the contacts between charged atoms. Further,
      the influence of sequence and structural parameters such as surrounding
      hydrophobicity, solvent accessibility, secondary structure, long-range order and
      conservation score has been discussed. CONCLUSION: The results obtained in the
      present work provide deep insights for understanding the interplay between
      stability and binding in protein-carbohydrate complexes.

PMID- 29473491
TI  - Effect of Laser Therapy on Defensins' Gene Expression in TR146 Epithelial Cell
      Line.
AB  - INTRODUCTION: Laser Therapy (LT) has been employed for the treatment of Oral
      Mucositis (OM) due to its anti-inflammatory, analgesic and bio-stimulatory
      effects. OBJECTIVE: This pilot study investigated the effect of LT on the
      expression of DEFB1, DEFB4, DEFB103 genes encoding for the human beta-defensins
      1, 2 and 3. MATERIALS AND METHOD: TR146 epithelial cell line, used to mimic oral
      mucosa, was irradiated with different LT protocols. beta-defensins gene
      expression was evaluated using TaqMan probes on Real- Time PCR platform. RESULTS
      AND CONCLUSION: In this cellular model LT decreased mRNA defensins' expression 30
      minutes after irradiation but not 24 hours later, suggesting that LT is able to
      influence beta -defensins production immediately after treatment, while its
      efficacy decreases over time.

PMID- 29473492
TI  - Metal ion complexes with pyrazoles, aziridines and diaziridines - synthesis and
      biological activity.
AB  - Heterocyclic compounds containing nitrogen ions, like pyrazoles, aziridines,
      diaziridines and their metal ion complexes with Cu(II), Zn(II) and Ru(III) and
      others exhibit a wide range of biological activity, including mainly anti
      inflammatory, antioxidant, anti-cancer, and antimicrobial properties. Biological
      significance of these molecules and thus their potential use in medicine has
      driven growing interest into their coordination chemistry. A knowledge of the
      relationship between the structure of chemical compounds and their activity is
      needed for the synthesis of the preparations possessing the most beneficial
      features. The choice of interposed substituents may improve biocidal and
      antitumor action, reduce the toxicity of the initial substance, or even
      completely eliminate its adverse effects for healthy tissues. The main aim of
      this review paper is to present the current state of knowledge concerning the
      synthesis and biological activity of complexes with small heterocyclic ligands
      containing transition metal ions.

PMID- 29473493
TI  - Current limitations in the treatment Parkinson's and Alzheimer's diseases: state
      of-the-art and future perspective of polymeric carriers.
AB  - Alzheimer's and Parkinson's disease are the most common neurodegenerative
      diseases worldwide and their incidence is increasing due to the aging population.
      At the moment, the available therapies are not disease modifying and have several
      limitations, some of which are discussed in this review. One of the main
      limitations of these treatments is the low concentration that drugs reach in the
      central nervous system after systemic administration. Indeed, the presence of
      biological barriers, particularly the blood brain barrier (BBB), hinders the
      effective drug delivery to the brain, reducing the potential benefit coming from
      the administration of the medication. In this review the mechanisms of transport
      across the BBB and new methods to improve drug passage across the BBB are
      discussed. These methods include non-invasive solutions such as intranasal and
      intravitreal administration, the use of nanotechnology solutions based on
      polymeric carriers when drug is intravenously injected, orally taken for
      intestine adsorption or delivered through the dermal mucosa. Also, it provides an
      analysis of more invasive solutions that include intracranially injected
      hydrogels and implanted devices for local drug delivery. Efforts in finding new
      therapeutic drugs blocking neurodegenerative disease progression or reverting
      their course should be coupled with efforts addressed to efficient drug delivery
      systems. Hence, new pharmacology discoveries together with advancements in
      nanotechnologies and biomaterials for regenerative medicine are required to
      effectively counteract neurodegenerative diseases.

PMID- 29473494
TI  - Protein Tyrosine Nitration in Lung Cancer: Current Research Status and Future
      Perspectives.
AB  - Oxidative/nitrative damage is a crucial element among the complex factors that
      contribute to lung carcinogenesis. Nitric oxide (NO) free radicals, through
      chemical modifications such as tyrosine nitration, are significantly involved in
      lung carcinogenesis and metastasis. NO-mediated protein nitration, which is the
      addition of the nitro group (-NO2) to position 3 of the phenolic ring of a
      tyrosine residue, is an important molecular event in lung cancer, and has been
      studied with mass spectrometry. Nitration is involved in multiple biological
      processes, including signal transduction, protein degradation, energy metabolism,
      mitochondrial dysfunction, enzyme inactivation, immunogenic response, apoptosis,
      and cell death. This article reviews the relationship of NO and its derivates and
      lung cancer, formation and roles of tyrosine nitration in lung cancer,
      differences of protein nitration between lung cancer and other inflammatory
      pulmonary diseases, current status of protein nitration and nitroproteomics in
      lung cancer, and future perspectives to achieve a better understanding of lung
      carcinogenesis, for biomarker discovery; and for new diagnostic and prognostic
      monitoring, and therapeutic targets.

PMID- 29473496
TI  - Modulation of Hepatic MRP3/ABCC3 by Xenobiotics and Pathophysiological
      Conditions: Role in Drug Pharmacokinetics.
AB  - Liver transporters play an important role in the pharmacokinetics and disposition
      of pharmaceuticals, environmental contaminants, and endogenous compounds. Among
      them, the family of ATP-Binding Cassette (ABC) transporters is the most important
      due to its role in the transport of endo- and xenobiotics. The ABCC sub-family is
      the largest one, consisting of 13 members that include the cystic fibrosis
      conductance regulator (CFTR/ABCC7); the sulfonylurea receptors (SUR1/ABCC8 and
      SUR2/ABCC9) and the multidrug resistance-associated proteins (MRPs). The MRP
      related proteins can collectively confer resistance to natural, synthetic drugs
      and their conjugated metabolites, including platinum-containing compounds, folate
      anti-metabolites, nucleoside and nucleotide analogs, among others. MRPs can be
      also catalogued into "long" (MRP1/ABCC1, -2/C2, -3/C3, -6/C6, and -7/C10) and
      "short" (MRP4/C4, -5/C5, -8/C11, -9/C12, and -10/C13) categories. While
      MRP2/ABCC2 is expressed in the canalicular pole of hepatocytes, all others are
      located in the basolateral membrane. In this review, we summarize information
      from studies examining the changes in expression and regulation of the
      basolateral hepatic transporter MPR3/ABCC3 by xenobiotics and during various
      pathophysiological conditions. We also focus, primarily, on the consequences of
      such changes in the pharmacokinetic, pharmacodynamic and/or toxicity of different
      drugs of clinical use transported by MRP3.

PMID- 29473495
TI  - Virtual Screening in Hepatitis B Virus Drug Discovery: Current Stateof- the-Art
      and Future Perspectives.
AB  - Hepatitis B Virus (HBV) is a major global health burden. Interferon alpha and
      nucleos(t)ide analogues are currently the standard-of-care for chronic HBV
      infection. However, these antiviral agents have limited efficacy and do not
      result in a sustained virological response in the majority of infected patients.
      Virtual Screening (VS) strategies have now a strong impact on drug discovery, the
      strength of this research field has been corroborated by recent contributions in
      the development of novel drug candidates which are in clinical trials or which
      are already available in the clinics. In this context, different VS strategies
      have been applied to HBV in order to discover novel inhibitors. In this review,
      we summarize the VS efforts to identify and design novel HBV interventions. We
      believe that the combination of in silico and in vitro tools can lead to faster
      validation of novel drug targets which could accelerate the HBV drug discovery
      and development efforts.

PMID- 29473497
TI  - Anti-NMDA Receptor Encephalitis: Efficacy of Treatment for Male Patients and
      miRNA Biomarker.
AB  - Treatments for the anti-NMDA receptor encephalitis usually include steroids,
      intravenous immunoglobulin, plasma exchange, plasmapheresis, rituximab,
      cyclophosphamide and tumor resection. We aimed to compare the efficacy of the
      treatments including intravenous immunoglobulin, plasma exchange, plasmapheresis,
      rituximab or cyclophosphamide for male anti-NMDA receptor encephalitis patients
      without tumor and to discuss potential biomarkers for this disease. The Fisher
      exact test and the contingency table analysis were used to analyze the treatment
      efficacy for both male and female these patients. A hierarchical tree method was
      adopted to analyze the difference of the treatment efficacy between male and
      female patients. The results revealed that the efficacy rate of plasmapheresis
      (or plasma exchange) is not inferior to those of intravenous immunoglobulin and
      rituximab (or cyclophosphamide) for male patients without tumor. In addition, B
      cell attracting C-X-C motif chemokine 13 (CXCL13) and microRNA let-7b are
      potential to be treatment response biomarkers for anti-NMDA receptor
      encephalitis. But they may not be useful prognostic biomarkers for this
      encephalitis unless they are not biomarkers for other autoimmune encephalitides.

PMID- 29473498
TI  - Functions and Evolution of Lhcb Isoforms Composing LHCII, the Major Light
      Harvesting Complex of Photosystem II of Green Eukaryotic Organisms.
AB  - Oxygenic photosynthesis provides energy and oxygen for almost all forms of life
      on earth. This process is based on the energy of photons, which is used to split
      water and use its electrons to reduce carbon atoms to create organic molecules
      and thus fix the light energy into a chemical form. Two photosytems working in
      series are involved in light harvesting and conversion. Both are multi-protein
      supercomplexes composed of a core complex, where the photochemical reaction takes
      place, and an antenna system involved in light harvesting. In plants and green
      algae, the antenna of photosystem II, the photosynthetic complex involved in
      water splitting, comprises the Light Harvesting Complex II (LHCII) trimers, the
      most abundant membrane protein on earth. LHCII is composed of highly conserved
      Lhcb isoforms and all green organisms count a high number of Lhcb. In vascular
      plants they are classified in three distinct subclasses, Lhcb1, 2 and 3, while in
      algae and non-vascular plants, these isoforms are less differentiated and called
      Lhcbm proteins. In this review, we compare LHCII proteins of different organisms,
      from green algae to angiosperms, and discuss the role of the modifications that
      occurred through evolution. We highlight the various functions of the different
      isoforms in photosynthesis, ranging from light harvesting, a common role to all
      these proteins, to regulations of photosynthesis that rely on specific isoforms.

PMID- 29473499
TI  - Natural Aristolochia Alkaloid Aristololactam-beta-D-glucoside: Interaction with
      Biomacromolecules and Correlation to the Biological Perspectives.
AB  - BACKGROUND: Natural aristolochia alkaloids have attracted the attention of both
      chemists and biologists from the stand point of their structural and
      pharmacological aspects. Many of the compounds isolated in this group are potent
      tumor inhibitors. These are divided into nitrophenanthrinic acid, phenanthrene
      lactams and isoquinoline alkaloids. A number of structure-activity studies have
      been performed on aristolochia alkaloids. Of particular interest is the molecule
      with the beta-D-glucoside moiety that has similarity to the clinical anticancer
      agent daunomycin. OBJECTIVE: The anticancer activity of aristololactam-beta-D
      glucoside has been thought to be due to its DNA and RNA binding activities among
      other actions. In this article we focus on the physicochemical property of this
      alkaloid and the structural and functional aspects of its binding to different
      nucleic acid and protein structures. METHODS: This review highlights a large
      number of biophysical studies employing various analytical techniques like
      absorbance, fluorescence, circular dichroism, thermal melting, viscosity, IR
      study, isothermal calorimetry and differential scanning calorimetry. RESULT: The
      detailed binding mechanism in terms of the structural and thermodynamic aspects
      at the molecular level has been discussed. CONCLUSION: This review enables to
      assess the high potential of developing aristololactam-beta-Dglucoside and
      related alkaloids as therapeutic agents.

PMID- 29473500
TI  - CRISPR-cas System as a Genome Engineering Platform: Applications in Biomedicine
      and Biotechnology.
AB  - Genome editing mediated by Clustered Regularly Interspaced Palindromic Repeats
      (CRISPR) and its associated proteins (Cas) has recently been considered to be
      used as efficient, rapid and site-specific tool in the modification of endogenous
      genes in biomedically important cell types and whole organisms. It has become a
      predictable and precise method of choice for genome engineering by specifying a
      20-nt targeting sequence within its guide RNA. Firstly, this review aims to
      describe the biology of CRISPR system. Next, the applications of CRISPR-Cas9 in
      various ways, such as efficient generation of a wide variety of biomedically
      important cellular models as well as those of animals, modifying epigenomes,
      conducting genome-wide screens, gene therapy, labelling specific genomic loci in
      living cells, metabolic engineering of yeast and bacteria and endogenous gene
      expression regulation by an altered version of this system were reviewed.

PMID- 29473501
TI  - A Novel Finding: Macrophages Involved in Inflammation Participate in Acute Aortic
      Dissection Complicated with Acute Lung Injury.
AB  - BACKGROUND: Little is known about the pathogenesis of acute lung injury (ALI)
      complicated with acute aortic dissection (AAD). OBJECTIVE: We aim to investigate
      the roles of macrophages-derived matrix metalloproteinase 9 (MMP9) in the
      development of ALI complicated with AAD and factors involved in the recruitment
      of macrophages. METHODS: This study included three parts: (i) Determination of
      serum MMPs, angiotensin II (AngII) and MCP-1 in patients with AAD complicated
      with ALI or AAD only, non-ruptured chronic aortic aneurysm patients or healthy
      volunteers using ELISA method. (ii) A novel AAD complicated with ALI model was
      established by infusing angiotensin II (AngII) to immature rats treated with beta
      aminopropionitrile monofumarate (BAPN) to identify the potential roles of MMP9
      and MCP-1 in AAD complicated with ALI. (iii) Cultured pulmonary microvascular
      endothelial cell (PMVEC) line was used to investigate how AngII was involved in
      the release of MCP-1 in rat pulmonary vascular endothelial cells. RESULTS: Serum
      MMP9, AngII and MCP-1 were remarkably elevated in patients with AAD complicated
      with ALI. The MMP9 expressed in pulmonary tissues was derived from macrophages.
      In the animal model, the release of MMP9 from macrophages finally resulted in
      ALI, while inhibition of MMP9 and MCP-1 contributed to decreased incidence of AAD
      complicated with ALI. In vitro experiments indicated that AngII triggered
      overexpression of MCP-1 in PMVECs by activating NF-kappaB signaling pathway.
      CONCLUSION: AAD complicated with ALI is highly associated with the macrophages
      infiltrating the pulmonary interstitial tissue and released MMP9 in response to
      angiotensin II. MCP-1 is closely related to the recruitment of macrophages.

PMID- 29473502
TI  - Exogenous Hydrogen Sulfide Protects SH-SY5Y Cells from OGD/RInduced Injury.
AB  - BACKGROUND: Cerebral ischemia reperfusion (CIR) injury is the main pathological
      mechanism of ischemia stroke, and oxidative stress (OS) plays a vital role during
      the process of CIR. Recent studies have found that OS can activate MAPK pathway,
      which mainly functions as a mediator of cellular stresses. It revealed that H2S
      may exhibit multiple biological functions as a neuroprotector through protecting
      against OS-induced neuronal injury. But how H2S can attenuate
      ischemia/reoxygenation injury through MAPK signaling is not clear. The protective
      mechanism of exogenous hydrogen sulfide (H2S) on oxygen glucose
      deprivation/reoxygenation (OGD/R) at physiological doses in SH-SY5Y cells were
      investigated in this study. METHODS: DCFH- DA probe is used to measure
      intracellular ROS, Real-time PCR and Western blot are used to detect the levels
      of p38 MAPK, ERK3 and Nrf2. CCK-8 is used to detect cell viability. RESULTS:
      Comparing with the normal control group, the expressions of ERK3, p38MAPK and
      Nrf2 mRNA in other three groups were downregulated at the beginning of 24h. After
      24h, the expressions of ERK3, p38MAPK and Nrf2 were upregulated significantly
      compared with the normal control group. When the cells were pretreated with
      200MUM NaHS at the beginning of 24h, the expressions of ERK3, p38MAPK and Nrf2
      were decreased much more significantly than OGD/R and NaHS groups. CONCLUSION:
      The present study demonstrated that exogenous H2S exerts a protective effect
      against OGD/R-induced injury by enhancing the activation of the ERK3, p38MAPK and
      Nrf2 mRNA.

PMID- 29473503
TI  - Genetic Variants Identified from GWAS for Predisposition to Type 2 Diabetes
      Predict Sulfonylurea Drug Response.
AB  - BACKGROUND: Several SNPs were identified through GWAS for their association with
      type 2 diabetes which has implications to pancreatic beta-cell physiology.
      OBJECTIVE: We aimed to study the role of risk alleles of TCF7L2, KCNJ11, CDKN2A,
      CDKAL1, IGF2BP2, SLC30A8 and KCNQ1 along with pharmacokinetic variants in
      response to sulfonylureas. METHOD: We performed a prospective study on 209 newly
      diagnosed subjects; treatment naive T2D subjects were recruited. Individuals were
      started with glibenclamide monotherapy and followed-up for 12 weeks. Genotyping
      was done, using PCR-RFLP and TETRA-ARMS PCR and confirmed by DNA sequencing.
      RESULTS: In univariate regression analysis, KCNJ11 (rs5219) was only the
      predictor for glibenclamide treatment failure. CONCLUSION: The present data
      suggests a possible role of KCNJ11 gene in altered response to glibenclamide.

PMID- 29473504
TI  - Immunotherapy in Non-Small Cell Lung Cancer: Biological Principles and Future
      Opportunities.
AB  - Immunotherapy aims to amplify the anticancer immune response through reactivation
      of the lymphocytic response raised against several tumor neo-antigens. To obtain
      an effective immune response, this therapeutic approach requires that a number of
      immunological checkpoints be passed, such as the activation of excitatory
      costimulatory signals or the avoidance of coinhibitory molecules. Among the
      immune checkpoints, the interaction of the membrane-bound ligand PD-1 and its
      receptor PD-L1 has received much attention because of remarkable efficacy in
      numerous clinical trials for various cancer types, including non-small cell lung
      cancer (NSCLC). However, several limitations exist with these therapeutic agents
      when used as monotherapy, with objective responses observed in only 30-40% of
      patients, with the majority of patients demonstrating innate resistance, and
      approximately 25% of responders later demonstrating disease progression. Recent
      developments in the understanding of cancer immunology have the potential to
      identify mechanisms of innate and acquired resistance to immune checkpoint
      inhibitors through translational research in human samples. This review focuses
      on the biological basic principles for immunological checkpoint blockade, and
      highlights the current status and the perspectives of this therapeutic approach
      in NSCLC patients.

PMID- 29473505
TI  - LASP1 in Tumor and Tumor Microenvironment.
AB  - The growing evidence shows that LIM and SH3 Domain Protein 1 (LASP1) is a multi
      functional protein that plays important role in forming cytoskeleton and
      prognostic marker in different cancers. LASP1 expression is correlated with the
      grade, size, and the metastasis of tumor in clinical samples. And the
      upregulation of LASP1 facilitates tumor cells proliferation, migration, and
      invasion perhaps through the interaction with cytoskeleton and increased nuclear
      translocation. The underlying mechanism of LASP1 on tumor is still in the initial
      stage; therefore, the signaling pathways in various tumors are specifically
      summarized to deepen the biological understanding of LASP1. This article
      systematically summarizes the current status of knowledge regarding the
      contribution of LASP1 in physiological and pathological processes, especially the
      progress in tumor. This article also gives an emphasized overview of LASP1 on the
      correlation with tumor microenvironment.

PMID- 29473506
TI  - Maturity-Onset Diabetes of the Young: An Overview with Focus on the Middle East.
AB  - Today, there are more than 32 million patients with diabetes in the Middle East
      (ME), the number is expected to double by 2040. In contrast to Europe and North
      America and despite the high prevalence of diabetes in ME, epidemiological data
      about incident and types of diabetes in the region is very limited. Maturity
      onset diabetes of the young (MODY) is a subtype of monogenic diabetes
      representing 2-5% of all diabetes patients. The disease is autosomal dominant
      mode of inheritance characterized by beta-cell malfunction below the age of 35
      years. To date, there are 15 different MODY forms that have been identified; each
      has a distinct genetic etiology. It is very common that MODY is misdiagnosed
      between with type 1 or type 2 diabetes. Hence, accurate genetic diagnosis is
      crucial to individualize the treatment and to improve glycaemia control. New
      technologies such as next-generation sequencing (NGS) offer an excellent
      alternative to screen and identify causative MODY mutations. In this review, we
      summarize the main clinical and genetic characteristics for each MODY form. In
      addition, we shed light on MODY studies that have been executed in the ME region.

PMID- 29473507
TI  - Oxidative Stress and Decreased Mitochondrial Superoxide Dismutase 2 and
      Peroxiredoxins 1 and 4 Based Mechanism of Concurrent Activation of AMPK and mTOR
      in Alzheimer's Disease.
AB  - BACKGROUND: Emerging evidence supports the hypothesis that metabolism dysfunction
      is involved in pathogenesis of Alzheimer's disease (AD). One aspect of metabolic
      dysfunction includes dysregulation of adenosine monophosphate kinase protein
      kinase (AMPK) and mammalian target of rapamycin (mTOR) metabolic axis, which is
      extensively present in some of the leading causes of AD such as cerebrovascular
      diseases, type 2 diabetes and brain ischaemic events. While the molecular basis
      underlying this metabolic dysregulation remains a significant challenge,
      mitochondrial dysfunction due to aging appears to be an essential factor to
      activate AMPK/mTOR signaling pathway, leading to abnormal neuronal energy
      metabolism and AD pathology. METHODS: Using immunofluorescent imaging by Lecia
      confocal microscopy, we analyzed the activation of AMPK/mTOR. Concurrently, the
      level of mitochondrial antioxidant enzymes of superoxide dismutase 2 (SOD2) and
      peroxiredoxin 1 and 4 (p1 and p4) along with protein and DANA oxidation were
      examined to in postmortem brains of AD (n= 8) and normal (n= 7) subjects to
      evaluate the metabolism dysfunction role in AD pathology. RESULTS: In spite of
      AMPK inhibitory control on mTOR, concurrent phosphorylation of AMPK and mTOR (p
      AMPK and p-mTOR) was observed in AD brains with high colocalization with
      hyperphosphorylated tau. Mitochondrial antioxidant enzymes of SOD2 and p1 and p4
      were substantially decreased in p-AMPK, p-mTOR and p-tau positive cells along
      with higher levels of DNA and protein oxidation. CONCLUSION: Collectively, we
      conclude that AMPK and mTOR metabolic axis is highly activated in AD brains.
      While the inhibitory link between AMPK and mTOR seems to be disrupted, we suggest
      oxidative stress as the underlying mechanism for concurrent activation of AMPK
      and mTOR in AD.

PMID- 29473508
TI  - Tolfenamic Acid Prevents Amyloid beta-induced Olfactory Bulb Dysfunction In Vivo.
AB  - BACKGROUND: Amyloid beta inhibits olfactory bulb function. The mechanisms
      involved in this effect must include alterations in network excitability,
      inflammation and the activation of different transduction pathways. Thus, here we
      tested whether tolfenamic acid, a drug that modulates several of these
      pathological processes, could prevent amyloid beta-induced olfactory bulb
      dysfunction. OBJECTIVE: To test whether tolfenamic acid prevents amyloid beta
      induced alterations in olfactory bulb network function, olfaction and GSK3beta
      activity. METHOD: The protective effects of tolfenamic acid against amyloid beta
      induced population activity inhibition were tested in olfactory bulb slices from
      adult mice, while tolfenamic acid and amyloid beta were bath-applied. We also
      tested the effects of amyloid-beta in slices obtained from animals pre-treated
      chronically (21 days) with tolfenamic acid. The effects of amyloid beta micro
      injected into the olfactory bulbs were also tested, after two weeks, on olfactory
      bulb population activity and olfaction in control and tolfenamic acid chronically
      treated animals. Olfaction was assessed with the odor-avoidance and the
      habituation/cross-habituation tests. GSK3beta activation was evaluated with
      Western-blot. RESULTS: Acute bath application of tolfenamic acid does not prevent
      amyloid beta-induced inhibition of olfactory bulb network activity in vitro. In
      contrast, chronic treatment with tolfenamic acid renders the olfactory bulb
      resistant to amyloid beta-induced network activity inhibition in vitro and in
      vivo, which correlates with the inhibition of GSK3beta activation and the
      protection against amyloid beta-induced olfactory dysfunction. CONCLUSION: Our
      data further support the use of tolfenamic acid to prevent amyloid beta-induced
      pathology and the early symptoms of Alzheimer Disease.

PMID- 29473509
TI  - Bis-coumarin Derivatives and Their Biological Activities.
AB  - Bis-coumarins have caused great interests in the recent years. These compounds
      exhibit diverse biological activities which are ascribed to their ability to
      exert noncovalent interactions with the various active sites in organisms. Some
      of them such as dicoumarolum and dicoumarol were approved for therapeutic
      purposes in clinical practice. Encouraged by the above facts, numerous
      biscoumarin derivatives have been synthesized and screened for their biological
      activities, and many of them showed promising potency. This review is focused on
      the biological potential of bis-coumarin derivatives with particular mention of
      those exhibiting antibacterial, anticoagulant, antiinflammatory, antiviral, anti
      parasite and antitumor activities, and their structure-activity relationships are
      also discussed.

PMID- 29473510
TI  - Synthesis and Antifungal Activity of Coumarins Derivatives Against Sporothrix
      spp.
AB  - Sporotrichosis is a serious public health problem in Brazil that affects human
      patients and domestic animals, mainly cats. Thus, the search for new antifungal
      agents is required also due to the emergence and to the lack of effective drugs
      available in the therapeutic arsenal. The aim of this study was to evaluate the
      in vitro antifungal profile of two synthetic series of coumarin derivatives
      against Sporothrix schenckii and Sporothrix brasiliensis. The three-components
      synthetic routes used for the preparation of coumarin derivatives have proved to
      be quite efficient and compounds 16 and 17 have been prepared in good yields. The
      inhibitory activity of nineteen synthetic coumarins derivatives 16a-i and 17a-j
      were evaluated against Sporothrix spp. yeasts and the most potent compounds were
      16b and 17i. However, according to concentrations able to inhibit (minimum
      inhibitory concentrations) and kill (minimum fungicidal concentrations) the
      cells, 17i was more effective than 16b against Sporothrix spp. Thus, 17i
      exhibited good antifungal activity against S. brasiliensis and S. schenckii,
      suggesting that it is an important scaffold for the development of novel
      antifungal agents.

PMID- 29473511
TI  - A UBI 31-38 Peptide-coumarin Conjugate: Photophysical Features, Imaging Tracking
      and Synergism with Amphotericin B Against Cryptococcus.
AB  - Cryptococcosis is a fungal disease of global significance for which new effective
      treatments are needed. The conjugation of the synthetic antimicrobial peptide
      fragment UBI 31-38 to a coumarin derivative showed to be an effective approach
      for the design of a novel anticryptococcal agent. In addition to antifungal
      activity, the conjugate exhibited intense fluorescence, which could be valuable
      for mechanistic investigations of this molecule. In this work, we studied the
      photophysical properties of the conjugate and confocal scanning laser microscopy
      was used to inspect the distribution of the peptide-coumarin conjugate in
      Cryptococcus cell. The synergism of this compound with amphotericin B or
      fluconazole against C. gattii and C. neoformans strains was also investigated.
      The results indicated that the fluorescent conjugate alone as well as its
      combination with amphotericin B are promising tools against cryptococcosis.

PMID- 29473512
TI  - The Role of Inflammatory Response in Stroke Associated Programmed Cell Death.
AB  - Stroke represents devastating pathology which is associated with a high morbidity
      and mortality. Initial damage caused directly by the onset of stroke, primary
      injury, may be eclipsed by secondary injury which may have a much more
      devastating effect on the brain. Primary injury is predominantly associated with
      necrotic cell death due to fatal insufficiency of oxygen and glucose. Secondary
      injury may on the contrary, lead apoptotic cell death due to structural damage
      which is not compatible with cellular functions or which may even represent the
      danger of malign transformation. The immune system is responsible for
      surveillance, defense and healing processes and the immune system plays a major
      role in triggering programmed cell death. Severe pathologies, such as stroke, are
      often associated with deregulation of the immune system, resulting in aggravation
      of secondary brain injury. The goal of this article is to overview the current
      knowledge about the role of immune system in the pathophysiology of stroke with
      respect to programmed neuronal cell death as well as to discuss current
      therapeutic strategies targeting inflammation after stroke.

PMID- 29473513
TI  - The Role of LRRK2 in Neurodegeneration of Parkinson Disease.
AB  - The leucine-rich repeat kinase 2 (LRRK2) gene and alpha-synuclein gene (SNCA) are
      the key influencing factors of Parkinson's disease (PD). It is reported that
      dysfunction of LRRK2 may influence the accumulation of alpha-synuclein and its
      pathology to alter cellular functions and signaling pathways by the kinase
      activation of LRRK2. The accumulation of alpha-synuclein is one of the main
      stimulants of microglial activation. Microglia are macrophages that reside in the
      brain, and activation of microglia is believed to contribute to neuroinflammation
      and neuronal death in PD. Therefore, clarifying the complex relationship among
      LRRK2, alpha-synuclein and microglials could offer targeted clinical therapies
      for PD. Here, we provide an updated review focused on the discussion of the
      evidence supporting some of the key mechanisms that are important for LRRK2
      dependent neurodegeneration in PD.

PMID- 29473514
TI  - The Role of VE-cadherin in Blood-brain Barrier Integrity Under Central Nervous
      System Pathological Conditions.
AB  - The blood-brain barrier (BBB) is a layer between the blood circulation and neural
      tissue. It plays a pivotal role in maintaining the vulnerable extracellular
      microenvironment in the neuronal parenchyma. Neuroinflammatory events can result
      in BBB dysregulation by disturbing adherens junctions (AJs) and tight junctions
      (TJs). VE-cadherin, as one of the most important components of the vascular
      system, is specifically responsible for the assembly of AJs and BBB architecture.
      Here, we present a review, which highlights recently available insights into the
      relationship between the neuroinflammation and BBB dysregulation. We then explore
      the specific interaction between VE-cadherin and BBB. Finally, we discuss the
      changes of VE-cadherin with different neurological diseases from both
      experimental and clinical studies. An understanding of VE-cadherin in BBB
      regulation may indicate that VE-cadherin can partially be a biomarker of
      neuroinflammation disease and lead to novel approaches for abating BBB
      dysregulation under pathological conditions and the opening of the BBB following
      central nervous system (CNS) drug delivery.

PMID- 29473516
TI  - The Essential Role of Primary Caregiver in Early Detection of Familial
      Hypercholesterolemia and Cardiovascular Prevention.
AB  - Familial hypercholesterolemia (FH) is a worldwide common autosomal inherited
      condition associated with premature cardiovascular diseases, both in men and in
      women (World frequency has been recently estimated to be as high as 1:250).
      Identifying FH cases early in life could represent a cornerstone to prevent fatal
      events in adult's life. Pediatricians are well positioned to evaluate the
      familial cardiovascular risk factors among their young patients, to make a
      diagnosis and to perform familial screening. The goal of this paper is therefore
      to emphasize the recognition of this genetic condition at a younger age and to
      initiate both familial screening and a safe treatment. Prevention of
      cardiovascular disease starts at an early age in all children, but it may save
      lives in FH patients.

PMID- 29473515
TI  - Updates on Genome-Wide Association Findings in Eating Disorders and Future
      Application to Precision Medicine.
AB  - Heterogeneity, frequent diagnostic fluctuation across presentations, and global
      concerns with the absence of effective treatments all encourage science that
      moves the field toward individualized or precision medicine in eating disorders.
      We review recent advances in psychiatric genetics focusing on genome-wide
      association studies (GWAS) in eating disorders. Given that the only eating
      disorder to be the subject of GWAS to date is anorexia nervosa, we review
      anorexia GWAS and enumerate the prospects and challenges of a genomics-driven
      approach towards personalized intervention in eating disorders.

PMID- 29473517
TI  - The Prevalence of Dyslipidemia and Other Cardiovascular Risk Factors in Youth
      with Diabetes.
AB  - BACKGROUND: Individuals diagnosed with diabetes mellitus have an increased risk
      of cardiovascular disease, often leading to premature morbidity and mortality. As
      the number of youth developing T1D and T2D continues to grow, early onset
      predisposes patients to a longer burden of disease and earlier onset of
      cardiovascular complications. Early identification and effective management and
      treatment of risk factors can lead to decreased cardiovascular events and
      improved quality of life. OBJECTIVE: In this study, we describe the prevalence of
      CVD risk factors in children with diabetes. RESULTS: 274 subjects were included
      in this study, all > 1 year since the time of diagnosis. 134 participants were
      male (49%). Mean age was 13.7 years (males); 12.8 years (females). subjects
      averaged 4 diabetes-related visits per year. At the time of their most recent
      clinic visit, 33% of subjects had a HbA1c < 8%, and 29% had a HbA1c > 10%.
      Greater than 50% of subjects were overweight or obese. A significant number of
      subjects were found to have dyslipidemia, and elevated blood pressure was common.
      DISCUSSION: CVD risk factors are common in children with diabetes mellitus. Good
      glycemic control, early identification, and effective life-long management of all
      CVD risk factors may help decrease the high rate of premature morbidity and
      mortality in diabetes.

PMID- 29473519
TI  - Identification of New Chromenone Derivatives as Cholinesterase Inhibitors and
      Molecular Docking Studies.
AB  - BACKGROUND: Alzheimer's Disease (AD) is the leading cause of dementia among the
      aging population. This devastating disorder is generally associated with the
      gradual memory loss, specified by a decrease of acetylcholine level in the cortex
      hippocampus of the brain due to hyperactivation of cholinesterases
      (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)). OBJECTIVE:
      Therefore, inactivation of AChE and BChE by inhibitors can increase the
      acetylcholine level and hence may be an encouraging strategy for the treatment of
      AD and related neurological problems. METHOD: In this contribution, two series of
      chromenone-based derivatives were tested by Ellmann's calorimetric method for
      AChE and BChE inhibition. RESULTS: All the compounds showed inhibitory activity
      against cholinesterases and some of them exhibited dual inhibition of AChE as
      well as BChE. The most potent inhibitor of AChE was 2l having an IC50 value of
      0.08 +/- 0.03 uM, while 3q inhibited the BChE with an IC50 value of 0.04 +/- 0.01
      uM. In case of dual inhibition, 3h showed an inhibitory concentration of 0.15 +/-
      0.01 uM for AChE, and 0.09 +/- 0.01 uM for BChE. Molecular docking studies were
      performed to explore the probable binding modes of the most potent dual
      inhibitors. CONCLUSION: It can be hypothesized that the inhibitors are able to
      target cholinesterase pathways and may emerge as a suitable outset for the
      further development process.

PMID- 29473518
TI  - Management of Measurable Variable Cardiovascular Disease' Risk Factors.
AB  - AIM: To summarize the main findings on variable cardiovascular risk factors and
      their management in everyday practice. METHODS: A narrative review of the
      relevant literature known to the authors and incorporation of healthy changes
      tips in defined variable cardiovascular risk factors. RESULTS: There are known
      variable cardiovascular risk factors to be claimed as those that should be
      changed in order to achieve a better prevention of cardiovascular disease
      development. But, most papers are informative and they didn't incorporate exact
      measures for each variable risk factor. Our paper shows exact measures for each
      variable cardiovascular risk factor that should be incorporate in everyday
      practice of family practitioners and cardiologists as well. CONCLUSION: The best
      cardiovascular disease' prevention should include a multidisciplinary team of
      experts and the entire community with the support of governmental and non
      governmental organizations that will contribute to improving the lifestyle of
      individuals and the entire community through their activities and legal
      provisions. The most important factors in cardiovascular disease management are:
      recognizing individual risk factors, monitoring them, and assisting in changes in
      life-style habits that directly affect the defined risk factors of a patient. The
      simplest and most practicable guidelines for CV prevention in accordance with the
      national, cultural and socioeconomic aspects of their country of work are needed.

PMID- 29473520
TI  - Synthesis and Biological Evaluation of 12N-substituted Tricyclic Matrinic
      Derivatives as a Novel Family of Anti-Influenza Agents.
AB  - BACKGROUND: Influenza is still a serious threat to human health with significant
      morbidity and mortality, so it is desirable to develop novel anti-flu drug agents
      with novel structures. OBJECTIVE: The main purpose of this research was to
      explore broad-spectrum anti-flu agents and provide antiviral stockpiles in
      response to potential future influenza pandemics. METHODS: Fifteen novel 12N
      substituted tricyclic matrinic derivatives were synthesized and evaluated for
      their anti-influenza activities against H1N1 subtype taking 12N-p
      cyanobenzenesulfonyl matrinane (1) as the lead. All prepared compounds were
      characterized by 1H NMR, 13C NMR and ESI-HRMS. The pharmacokinetics (PK) profile
      of the key compound was also examined in this study. RESULT: The structure
      activity relationship study indicated that suitable benzyl groups on 12N atom
      might be beneficial for the activity. Among them, 12N-p-carboxybenzyl matrinic
      butane (17g) exhibited the most promising activity with an IC50 value of 16.2 uM
      and a selective index (SI) value of over 33.4. In addition, compound 17g
      displayed a good in vivo pharmacokinetic profile with an area under the curve
      (AUC0-infinity) value of 9.89 uM.h. CONCLUSION: We consider tricyclic matrinic
      butane derivatives to be a new class of anti-influenza agents and this study
      provided useful information on further optimization.

PMID- 29473521
TI  - Synthesis of Oleanolic Acid Analogues and Their Cytotoxic Effects on 3T3 Cell
      Line.
AB  - BACKGROUND: Oleanolic acid (OA) is a known natural compound with many important
      biological activities. Thirteen oleanolic acid derivatives linked at C-3 and C-28
      were synthesized and their structures were confirmed by 1H- and 13C NMR and mass
      spectral analyses. Among them, compounds 4, 6, 8-10, 12, 13 were synthesized for
      the first time. They were evaluated for their cytotoxic activity. They showed
      proliferative effect at low concentrations while cytotoxic effect was observed at
      high concentrations in a dose dependent manner. METHODS: We have first
      synthesized compounds 1 and 2 from the reaction of methyl iodide and OA. Compound
      1 was reduced with LiAlH4 to give compound 3, and compound 2 gave compound 9 with
      MOMBr as a new compound. The compound 10 was then obtained from the reduction of
      compound 9 with LiAlH4 as a new oleanolic acid derivative. A diol derivative 11
      was synthesized from OA and LiAlH4 at the room temperature. Compound 4 was
      obtained from the reaction of compound 3 with CBr4 as a new analogue of OA, and
      the reduction of compound 4 afforded compound 5 as a known product. In addition,
      we synthesized compounds 6-8 from compound 3 using MsCl, MeI and p-nitrobenzoyl
      chloride, respectively, in good yields. Compounds 6 and 8 are new analogues of
      OA. The new compounds 12 and 13 were also synthesized starting from OA using with
      MOMBr and TBDMSiCl as the reagents. The all synthesized compounds were purified
      by using column chromatography and/or crystallization. RESULTS: In the present
      study, thirteen OA derivatives linked at C-28 and (or) C-3 were synthesized and
      evaluated for their cytotoxic activity on 3T3 cell lines which are the standard
      fibroblast cell lines, derived from Swiss albino mouse embryo tissue. 3T3 cell
      viability was observed at low concentrations of the tested triterpenoids while
      they displayed anti-proliferative effect at higher concentrations. CONCLUSION:
      Oleanolic acid 28-methyl ester (2) showed fairly different behavior from all the
      other compounds tested and found to be the least cytotoxic compound. However, at
      200 uM concentration, it exhibited the same cytotoxicity with compounds 3, 9 and
      10 around 58-59%. Among the tested 13 compounds, 7 exhibited the most drastic
      decline for the viability from 12,5 uM to 25 uM concentration. Compound 6
      displayed the most cytotoxic effect, almost in all concentrations, particularly
      at 6.25 and 25 uM concentrations while the highest cytotoxic effect at 50 uM was
      observed for compound 11 among all the tested triterpenoids. As a result, all the
      tested OA derivatives showed proliferative effect at 1,56 uM although no
      proliferative effect was observed for OA. Moreover, OA exhibited higher cytotoxic
      effect than its derivatives, particularly at higher concentrations (50, 100, 200
      uM) with an exception for compound 11. Because, the latter showed highest
      proliferative effect at lowest concentration, and highest anti-proliferative
      effect at highest concentration which surpassed all the OA derivatives.

PMID- 29473522
TI  - An Evidence-Based Review of Off-Label Uses of Polidocanol.
AB  - BACKGROUND: Polidocanol is approved for its competence in the treatment of
      varicose veins and spider veins; however, unfortunately, many of its off-label
      uses are still underappreciated. OBJECTIVE: Lack of an appropriate comprehensive
      review for off-label uses of this medication troubles physicians about making
      evidence-based decisions on prescribing it for its various outstanding off-label
      uses. This article attempts to provide physicians with the latest information
      concerning successful and unsuccessful use of polidocanol as an alternative
      treatment for esophageal and gastric varices, tendinopathy and epicondylitis,
      vascular malformations, varicocele, hydrocele and spermatocele, aneurysmal bone
      cysts, itching, management of gastrointestinal bleeding, simple renal cysts,
      reducing the incidence and severity of radio-induced dermatitis and hemorrhoids.
      METHOD: The two databases of MEDLINE and Cochrane Library were searched for all
      human English studies, published in January 2006 to November 2017, which
      contained the keyword of "polidocanol" or its alternative MeSH terms. RESULTS:
      Our search identified a total number of 597 articles. Those articles that were
      only discussing the approved uses of polidocanol were excluded and the remaining
      116 articles were reviewed. Eleven major and 30 minor off-label uses were found
      within included studies. CONCLUSION: Numerous successful administrations of this
      drug in a variety of clinical conditions lead to promising perspectives toward
      it. Sclerotherapy with polidocanol as a minimal-invasive method (having similar
      outcomes like the prevalent surgeries) may reduce the rate of complications.
      Furthermore, for determining the most appropriate method and dosage, randomized
      clinical trials are needed, confirming and providing more clear instructions for
      different conditions.

PMID- 29473523
TI  - Drug-induced QT Interval Prolongation in the Intensive Care Unit.
AB  - BACKGROUND: The most common acquired cause of Long QT syndrome (LQTS) is drug
      induced QT interval prolongation. It is an electrophysiological entity, which is
      characterized by an extended duration of the ventricular repolarization.
      Reflected as a prolonged QT interval in a surface ECG, this syndrome increases
      the risk for polymorphic ventricular tachycardia (Torsade de Pointes) and sudden
      death. METHOD: Bibliographic databases as MEDLINE and EMBASE, reports and drug
      alerts from several regulatory agencies (FDA, EMEA, ANMAT) and drug safety guides
      (ICH S7B, ICH E14) were consulted to prepare this article. The keywords used
      were: polymorphic ventricular tachycardia, adverse drug events, prolonged QT,
      arrhythmias, intensive care unit and Torsade de Pointes. Such research involved
      materials produced up to December 2017. RESULTS: Because of their mechanism of
      action, antiarrhythmic drugs such as amiodarone, sotalol, quinidine,
      procainamide, verapamil and diltiazem are associated to the prolongation of the
      QTc interval. For this reason, they require constant monitoring when
      administered. Other noncardiovascular drugs that are widely used in the Intensive
      Care Unit (ICU), such as ondansetron, macrolide and fluoroquinolone antibiotics,
      typical and atypical antipsychotics agents such as haloperidol, thioridazine, and
      sertindole are also frequently associated with the prolongation of the QTc
      interval. As a consequence, critical patients should be closely followed and
      evaluated. CONCLUSION: ICU patients are particularly prone to experience a QTc
      interval prolongation mainly for two reasons. In the first place, they are
      exposed to certain drugs that can prolong the repolarization phase, either by
      their mechanism of action or through the interaction with other drugs. In the
      second place, the risk factors for TdP are prevalent clinical conditions among
      critically ill patients. As a consequence, the attending physician is expected to
      perform preventive monitoring and ECG checks to control the QTc interval.

PMID- 29473524
TI  - Pharmacogenetics of Glucagon-like Peptide-1 Agonists for the Treatment of Type 2
      Diabetes Mellitus.
AB  - BACKGROUND: Pharmacogenetics is a promising area of medical research, providing
      methods to identify the appropriate pharmaceutical agent and dosing for each
      unique patient. Glucagon- like peptide-1 (GLP-1) agonists are a novel therapeutic
      choice used in the treatment of type 2 diabetes mellitus (T2DM), demonstrating
      efficacy regarding glycemic control and weight loss. Therapeutic response to GLP
      1 agonist treatment is a complex biophenomenon, dependent on a plethora of
      modifiable (diet, exercise, adherence) and non-modifiable (genetic individual
      variants, ethnic characteristics) parameters. Iotan this context, it has been
      hypothesized that genetic polymorphisms of GLP-1 related genes may be associated
      with the therapeutic response to GLP-1 agonist treatment. This review focuses on
      the most important polymorphisms of the GLP-1 biological network that could
      affect clinical response to GLP-1 agonist treatment. METHODS: Biomedical
      databases were searched to identify key articles in the field and their results
      are critically presented in this review. RESULT: Recent pharmacological and
      clinical studies demonstrated a significant variation in GLP-1 agonist treatment,
      in cohorts with homogeneous adherence to diet, exercise and antidiabetic
      treatment. These studies identified several cases of non-responders to GLP-1
      agonist therapy, in association with specific allelic patterns of GLP-1 receptor
      or other biomolecules implicated in glucose homeostasis. CONCLUSION: Although the
      exact DNA sequences that cause the molecular changes leading to a variable
      response to GLP-1 agonists have not been yet fully identified, these findings
      underline the importance of an individualized approach in anti-diabetic
      treatment.

PMID- 29473525
TI  - Oral Mucosal Stem Cells, Human Immature Dental Pulp Stem Cells and Hair Follicle
      Bulge Stem Cells as Adult Stem Cells Able to Correct Limbal Stem Cell Deficiency.
AB  - BACKGROUND: Adult stem cells are somatic stem cells distributed all over the
      body. They represent a promising future for regenerative medicine because of
      their multiple advantages as they are widely available, accessible, easily stored
      and manipulated to a wide range of cells and with minimal invasive extraction.
      OBJECTIVE: This review describes three examples of adult stem cells: oral mucosal
      epithelial stem cells, human immature dental pulp stem cells and hair follicle
      bulge stem cells that show an ability to correct limbal stem cell deficiency,
      their isolation and cultivation methods, feeder layers, carriers, markers
      expressed, successfulness to regenerate the ocular surface and mimic the corneal
      function in LSCD. CONCLUSION: Although hair follicle bulge stem cells and human
      immature dental pulp stem cells are a promising adult stem cell source to correct
      limbal stem cell deficiency, but the published research evaluating this ability
      is limited. Therefore, this article emphasize further research in this area.

PMID- 29473526
TI  - There is no difference between sequences of HIV-1 infected patients with stable
      clinical status and HIV-1 reference sequence.
AB  - BACKGROUND: The rate of human immunodeficiency virus type 1 (HIV-1) infection in
      Iran has increased dramatically in the past few years. HIV-1 genome sequences are
      pivotal for large-scale studies of inter- and intra-host evolution. To understand
      the molecular difference between reference HIV-1 isolate and two HIV-1 infected
      patients in Iran, we conducted this study to analyze some genome segments of
      Iranian HIV-1 isolates. METHODS: Two HIV-1-infected individuals who were under
      antiretroviral therapy (ARV) for 8 years with stable clinical status were
      enrolled. Gag-Pol genome sequences (4500 nt) obtained from patient's plasma
      samples were used for constructing phylogenetic tree and analyzing similarity
      plotty. RESULTS: Both isolates belonged to CRF35_AD subtype. One of them had drug
      resistance. Our patient's HIV genome and protein isolates showed no clear
      difference with genome and protein sequences of reference sequence. CONCLUSIONS:
      our patient's stable clinical status had no connection to genome sequence; it
      could be owing to immunological factors or other patient's mode which are still
      unknown.

PMID- 29473527
TI  - Glucose Lowering Activity of Anvillea Radiata Coss & Durieu in Diabetic Rats.
AB  - INTRODUCTION: Anvillea radiata Coss. & Durieu (Asteraceae) is an endemic plant
      from North Africa (Morocco and Algeria). This plant has many traditional uses
      including treatment of obesity and diabetes. AIM OF THE STUDY: The study aims to
      evaluate the antidiabetic effect of aqueous extract of Anvillea radiata (A.
      radiata) leaves on both normal and streptozotocin (STZ)-induced diabetic rats
      treated at a dose of 10 mg/kg body weight for fifteen days. In addition, a
      preliminary pytochemical screening for various components was realized. RESULTS:
      The blood glucose levels were lowered in diabetic rats treated with A. radiata,
      but no effect was observed in normal rats. Single oral administration of A.
      radiata reduced blood glucose levels from 22.15+/-0.98 mmol/L to 14.00+/-1.89
      mmol/L (p<0.0001) six hours after administration in STZ diabetic rats.
      Furthermore, blood glucose levels were decreased from 22.15+/-0.98 mmol/L to
      4.39+/-1.29 mmol/L (p< 0.0001) in STZ diabetic rats after fifteen days of
      treatment. According to the oral glucose tolerance test, the A. radiata (10
      mg/kg) was shown to significantly prevent the increase in blood glucose levels in
      normal treated rats 30 min, 60 min and 120 min after glucose administration when
      compared to the control group. Concerning the preliminary phytochemical screening
      of A. radiata, several compounds of chemicals have been found such as
      polyphenols, flavonoids, tannins, mucilage, sesquiterpenes, terpenoids and
      carbohydrates. CONCLUSION: The results show that aqueous extract of A. radiata
      leaves possesses a significant antihyperglycemic activity.

PMID- 29473528
TI  - Novel Genetic Tool to Study the Stability of Genomic Islands.
AB  - BACKGROUND: Genomic islands (GIs) are discrete segments of mobile DNA with
      defined boundaries according to recent patents, acquired in the bacterial genome
      from another organism by horizontal gene transfer during the course of evolution.
      GIs contribute significantly to virulence, disease development, antimicrobial
      resistance and metabolic process. OBJECTIVE: The present study focuses on the
      development of a vector based genetic tool carrying selectable and counter
      selectable markers, in order to flag the GIs in the bacterial chromosome and
      monitor their stability under in vitro and in vivo conditions. METHOD: We
      engineered suicide vectors, pSB40 and pSB41, carrying single or tandem copies of
      chloramphenicol acetyltransferase (cat) and levansucrase (sacB) alleles,
      respectively. The sacB-cat allele in both the vectors is flanked by several
      restriction sites. To test the suitability of sacB-cat allele for monitoring GI
      loss, we introduced the allele in the Vibrio Pathogenicity Island-1 (VPI-1) in
      Vibrio cholerae genome. RESULTS: The V. cholerae strain carrying sacB-cat allele
      in VPI-1 element showed resistance to chloramphenicol and sensitivity to sucrose
      at optimal growth conditions. Loss of VPI-1 element from the V. cholerae genome
      was simply monitored by growing the cells on selection agar plates supplemented
      with sucrose. Our results showed that the genetic tool we developed is suitable
      for monitoring GI stability in the bacterial genome. CONCLUSION: The present
      study indicates that pSB40 and pSB41are efficient and sensitive genetic tool that
      can be used for reverse genetics experiments and monitoring stability of mobile
      genetic elements in the bacterial genome.

PMID- 29473529
TI  - Application of Cocrystallization Approach in Drug Development: Recent Patents
      Review.
AB  - BACKGROUND: Cocrystals of active pharmaceutical ingredient has been of interest
      in the field of pharmaceutical research due to their potential for tailoring the
      physicochemical properties of pharmaceutical molecules. The increase in number of
      cocrystals screening experiments being reported and simultaneously the draft
      guidelines issued from regulatory bodies on pharmaceutical cocrystals provide the
      evidence of the acceptance of cocrystals in the drug development. This review
      presents the numerous patents addressing the key properties of an active
      pharmaceutical ingredient namely solubility and stability towards varied
      environmental conditions, being modified using suitable coformer and appropriate
      cocrystallization technique. METHODS: A literature review was conducted to
      summarize the reported articles as well as patents that have been published
      and/or granted for work related to cocrystallization of an active pharmaceutical
      ingredient (API). Efforts have been made to include examples for various types of
      objectives undertaken by the researchers to cocrystallize an API. RESULTS: The
      summary of the various cocrystallization techniques reported in peer reviewed
      journals shows that a majority of the articles till date prefer and explore the
      slow solvent crystallization technique compared to solid-state mediated
      processes. Amongst all the patents summarized in the review article, 37 patents
      have been published along with the improvement in physicochemical properties of
      the API whereas 35 patents have been reported only for the process of preparation
      of the API. CONCLUSION: The contents of the review very well highlight the ever
      increasing scope for the cocrystallization technique of an API, the varied
      methodologies applied for cocrystallization and the properties that can be
      improved by cocrystallization.

PMID- 29473530
TI  - Allergoids for Allergy Treatment.
AB  - BACKGROUND: Chemically modified allergen extracts, known as allergoids, are
      commonly used for treating allergic patients. In general terms, the concept of
      allergoids implies allergen extracts with a reduction of their allergenicity
      maintaining their immunogenicity. Different methods to obtain allergoids have
      been developed in the past years, opening attractive lines of research.
      OBJECTIVE: To review the different approaches to allergoid development as well as
      their characterization, mechanism of action and efficacy and safety issues.
      METHODS: A revision and analysis of the different types of allergoids has been
      performed, with special attention to patents submitted and granted in the last
      years. Additionally, updated information about the mechanism of action and
      clinical evidence and safety of allergoids has been discussed. RESULTS:
      Principally, allergoids are obtained by the polymerization of native allergen
      extracts with aldehydes, including formaldehyde or glutaraldehyde. However,
      recent patents and publications about different chemical modifications have been
      presented, as well as about the use of new adjuvants with allergoids. Regarding
      the characterization, allergoids require more sophisticated analytical methods
      than native extracts, as a consequence of their properties and characteristics.
      CONCLUSION: In the last years, the partial understanding of the mechanism of
      action and the generation of clinical evidence of different types of allergoids,
      linked to their excellent safety profile and their convenience for a quick build
      up phase, have made of allergoids an excellent product for allergy treatment.

PMID- 29473531
TI  - Diabetic Complications and Insight into Antidiabetic Potentialities of Ethno-
      Medicinal Plants: A Review.
AB  - BACKGROUND: The naturally inspired treatment options for several disease
      conditions and human-health related disorders such as diabetes mellitus have
      gained considerable research interest. In this context, naturally occurring
      plants and herbs with medicinal functionalities have gained special place than
      ever before in the current medicinal world. OBJECTIVE: The objective of this
      review is to extend the current knowledge in the clinical field related to the
      diabetic complications. A special focus has also been given to the anti-diabetic
      potentialities of ethnomedicinal plants. METHOD: Herein, we reviewed and compiled
      salient information from the authentic bibliographic databases including PubMed,
      Scopus, Elsevier, Springer, Bentham Science and other scientific databases. The
      patents were searched and reviewed from http://www.freepatentsonline.com.
      RESULTS: Diabetes mellitus is a group of metabolic disorders associated with the
      endocrine system that resulted in hyperglycemic conditions. Metabolic disorders
      can cause many complications such as neuropathy, retinopathy, nephropathy,
      ischemic heart disease, stroke, and microangiopathy. Traditional botanical
      therapies have been used around the world to treat diabetes. Among several
      medications and different medicines, various herbs are known to cure and control
      diabetes; also have no side effects. History has shown that medicinal plants have
      long been used for traditional healing around the world to treat diabetes. More
      than 800 plants around the world are shown by ethnobotanical information as
      traditional remedies for the treatment of diabetes. Several parts of these plants
      have been evaluated and appreciated for hypoglycemic activity. Medicinal plants
      have been found to be more effective than conventional drug compounds with
      no/fewer side effects and relatively inexpensive. In this review paper, we have
      reviewed plants with anti-diabetic and related beneficial medicinal effects.
      CONCLUSION: This review may be helpful for researchers, diabetic patient and
      decision makers in the field of ethnobotanical sciences. These efforts may also
      provide treatment to everyone and focus on the role of traditional novel medicine
      plants that have anti-diabetic abilities.

PMID- 29473532
TI  - The Promising Pharmacological Effects and Therapeutic/Medicinal Applications of
      Punica Granatum L. (Pomegranate) as a Functional Food in Humans and Animals.
AB  - BACKGROUND: Punica granatum L. (pomegranate), is a shrub mostly available in the
      Mediterranean Sea region. The fruits have gained the substantial attention among
      researchers due to their promising biological activities including anti
      inflammatory, antibacterial, antidiarrheal, immune modulatory, antitumor, wound
      healing and antifungal that have been attributed to various constituents of
      seeds, bark, juice, pericarp, and leaf of this tree across the globe. The
      phenolic compounds of pomegranate have been documented to possess numbers of
      prophylactic and therapeutic utilities against various pathological infections as
      well as non-infectious disorders. OBJECTIVE: The current review expedites the
      pharmacological role of Punica granatum L. in curing elements related to
      infectious and non-infectious disorders. METHODS: The current review is based on
      literature and patents already available on various scientific databases
      highlighting the role of Punica granatum along with its therapeutic potentials
      against infectious and non-infectious disorders. The databases included under
      study were PubMed, Med line, PubMed Central, Science Direct and few other
      scientific databases. The information obtained through these diverse databases is
      compiled, critically interpreted and presented in the current study. RESULTS:
      Multi-dimensional beneficial application of pomegranate plant is recorded. The
      pomegranate seed oil has phytoestrogenic compounds and the fruit is rich in
      phenolic compounds with strong antioxidant activity. The fruit and bark of
      pomegranate are used against intestinal parasites, dysentery, and diarrhea in
      different animals and human models. Since the ancient time the juice and seeds
      had considered the best therapy for throat and heart disorders. Ellagic acid is
      one of the main components of pomegranate with potent antioxidant activity.
      Results from different studies reported that Punica granatum L or its byproducts
      can be used as natural food additives in human and animal nutrition in order to
      boost immunity, microbial safety and provide the housing environment without
      affecting body weight gain. In addition, Punica granatum L. byproducts can
      modulate immune function and gut microbiota of broiler chickens as well as reduce
      the odorous gas emissions from excreta. Naturally occurring polyphenols in a
      pomegranate can be a potential alternative medicine for the prevention of avian
      Colibacillosis diseases and can also be used as an intestine astringent to
      relieve diarrhea and enteritis in chickens. CONCLUSION: The present review gives
      the insight towards major components of pomegranate as well as their
      pharmacological activities against pathological disorders. In spite of many
      beneficial properties of Punica granatum L., more research evidence on a
      molecular basis is needed to find out the molecular mechanism of action in
      various animals and human models to validate the usefulness of Punica granatum L.
      as a potent therapeutic agent.

PMID- 29473533
TI  - Biological Activities of Red Propolis: A Review.
AB  - BACKGROUND: The red propolis (RdProp) is a resin produced by Apis mellifera bees,
      which collect the reddish exudate on the surface of its botanic source, the
      species Dalbergia ecastophyllum, popularly known in Brazil as "rabo de bugio".
      Considered as the 13th type of Brazilian propolis, this resin has been gaining
      prominence due to its natural composition, rich in bioactive substances not found
      in other types of propolis. OBJECTIVE: This review aims to address the most
      important characteristics of RdProp, its botanical origin, the main constituents,
      its biological properties and the patents related to this natural product.
      METHOD: By means of the SciFinder, Google Patents, Patus(r) and Spacenet,
      scientific articles and patents involving the term "red propolis" were searched
      until August 2017. RESULTS: A number of biological properties, including
      antimicrobial, anti-inflammatory, antiparasitic, antitumor, antioxidant,
      metabolic and nutraceutical activities are attributed to RdProp, demonstrating
      the great potential of its use in the food, pharmaceutical and cosmetics
      industries. CONCLUSION: The available papers are associated to pharmacological
      potential of RdProp, but the molecular mechanisms or bioactive compounds
      responsible for each activity have not yet been fully elucidat ed. The RdProp
      patents currently found are directed to components for the pharmaceutical
      industry (EP2070543A1; WO2014186851A1; FR3006589A1; CN1775277A; CN105797149A;
      CN1879859A), cosmetic (JP6012138B2; JP2008247830A; JP6012138B2) and food
      (JP5478392B2; CN101380052A; WO2006038690A1).

PMID- 29473535
TI  - An Overview of Hepatoprotective Effects of Thymoquinone.
AB  - BACKGROUND: Liver diseases are globally recognized as major medical problems.
      Several species of herbal medicine have been investigated for the management of
      liver-related diseases. OBJECTIVE: In this context, Thymoquinone (TQ) as the main
      constituent of Nigella sativa has long been focused for the treatment of liver
      diseases in recent years. To suppressing liver diseases, it was reported that TQ
      exhibits hypolipidic effects, which prevented the fatty acid accumulation in the
      hepatocytes. The other activity of TQ, not only in the management of chronic
      liver diseases but also regarding the carcinogenesis, is its potent antioxidant
      effects, which affect several signaling pathways. RESULT: The effect of TQ on NF
      kappabeta is the hepatoprotective effect of this flavonoid. Recently, a few
      patents of TQ derivatives for protective effects have been developed. This
      article also discusses our findings with the patents for this agent. CONCLUSION:
      The present review purposed that although the experimental studies indicated the
      beneficial effects of TQ against liver diseases, more designed clinical trials in
      human are needed to confirm the safety and efficacy of TQ.

PMID- 29473534
TI  - The Enriched Proanthocyanidin Extract of Ligaria cuneifolia Shows a Marked
      Hypocholesterolemic Effect in Rats Fed with Cholesterol-Enriched Diet.
AB  - BACKGROUND: Ligaria cuneifolia (Lc) (R. et P.) Tiegh. (Loranthaceae) (Argentine
      mistletoe) is usually used in local folk medicine. OBJECTIVE: We studied the
      effect of treatment with the Lc proanthocyanidin-enriched fraction (PLc) in rats
      fed with Cho-enriched diet on plasma lipids levels, the hemorheological
      parameters, and biliary secretion. METHOD: Adult male Wistar rats were fed ad
      libitum with a Cho-enriched diet (Cho (97% purity) 8 g/kg of diet and corn oil
      280 g/kg of diet) during 28 days. Then, were separated in six experimental groups
      (n=5 each one), which were injected ip every 24 h with: 1) saline solution
      (control group, C) and 2) PLc, 3 mg/100 g body weight (treated group, C+PLc),
      during 3, 7 and 10 days. Group C presented an increase in plasma levels of Cho
      and Triglycerides (TG), and also, accumulation of hepatic lipid droplets. Also,
      cell shape and their corresponding morphological index (MI) were altered too.
      RESULTS: The treatment with PLc at 3, 7 and 10 days produces a diminution in the
      plasma Cho, LDL-Cho and serum TG levels, accompanied by a diminution of the lipid
      accumulation in the liver. The rates of bile acid output in bile can explain the
      diminution of plasma Cho, evidencing that some of the enzymes involved in the
      cholesterol conversion into bile acids could be up regulated by the treatment
      with PLc, leading to the observed increase bile flow. PLc treatment leads to a
      diminution of plasma levels of Cho and TG. CONCLUSION: Essentially, the treatment
      with PLc, despite the duration produces a modification in hemorheological
      parameters approaching the values of the experimental group with standard diet.
      Plasma levels of Cho, LDL-Cho and TG represent selected markers to evaluate the
      effect of enriched extract from Ligaria cuneifolia. Further work is necessary to
      better evaluate the mechanisms by which PLc induces modifications in the lipids
      metabolism.

PMID- 29473536
TI  - [Dermatomyositis as a paraneoplastic syndrome].
AB  - BACKGROUND: Dermatomyositis is an idiopathic inflammatory myopathy with an
      incidence of 1 in 100,000. Clinically, it features typical skin abnormalities and
      muscle weakness. In a subset of cases an underlying malignancy may be present; in
      such instances the term paraneoplastic syndrome is used. CASE DESCRIPTION: We saw
      a 75-year-old male with progressive skin abnormalities, especially on the chest
      and hands. In addition, he experienced weakness in his arms and legs. Three
      months earlier, he was diagnosed with prostate cancer. Following additional
      investigations, the diagnosis of dermatomyositis was made and treatment with
      prednisone proved successful. CONCLUSION: In a patient with typical skin
      abnormalities one should consider dermatomyositis and it is important to
      investigate for the presence of muscle disorders and occult malignancy. The
      muscle symptoms often respond well to prednisone, but the skin abnormalities are
      usually harder to resolve, Treatment of a possible underlying malignancy also
      influences the dermatomyositis.

PMID- 29473537
TI  - [Dilemma: to test or not to test for Lyme borreliosis in general practice].
AB  - There is no such thing as a perfect diagnostic test and the value of a test
      depends on the situation in which the test is being used. Here, we discuss two
      options for dealing with the diagnostic process for Lyme borreliosis in general
      practice. One option is to manage, treat or refer according to clinical signs and
      symptoms, in accordance with Dutch practice guidelines. The other option is to
      use laboratory tests to guide further patient management (treatment or referral).
      The choice depends on currently unknown factors, such as the pre-test probability
      of Lyme disease in patients presenting to general practitioners. Furthermore,
      clarity is required about how to proceed after a positive or negative test
      result. The consequences of a false test result will depend on the patient's
      status, possible alternative diagnoses and treatment options. Both physician and
      patient should be aware of the shortcomings of diagnostic tests.

PMID- 29473538
TI  - [A woman with swelling and blue-red discolouration of the leg].
AB  - A 61-year-old woman presented with a sudden marked swelling and blue-red
      discolouration of her entire left leg. The diagnosis phlegmasia cerulea dolens
      was made. This is an extreme case of lower-extremity deep venous thrombosis that
      can cause critical limb ischaemia and possible limb loss.

PMID- 29473539
TI  - [Myositis: more than a muscle disease].
AB  - Idiopathic inflammatory myopathy (IIM), commonly referred to as "myositis", is a
      rare but treatable auto-immune disease that is often misdiagnosed or diagnosed
      after significant delay. Using three clinical case reports as introductory
      examples, an overview is given - and pitfalls are discussed - of the diagnosis
      and treatment of myositis. Disease features are often extra-muscular in nature,
      may vary considerably between patients, and are frequently non-specific. Myositis
      related morbidity is high and myositis can be fatal, mainly due to cancer and
      interstitial lung disease. As such, we stress the importance of early recognition
      of this severe disease and timely referral of a patient with a (suspected) IIM to
      a multidisciplinary team for optimal diagnosis and disease management.

PMID- 29473540
TI  - [Prevention of postoperative infections: patient safety subordinated to
      antibiotic stewardship].
AB  - A new Dutch guideline for surgical antimicrobial prophylaxis recommends
      preoperative treatment with mupirocin and chlorhexidine showers only in patients
      identified as nasal carriers of Staphylococcus aureus. Yet, preoperative
      screening and treatment may not be achieved in many patients, because of the
      infrastructural complexity of all procedures this requires. We are therefore
      pleading for a universal treatment approach, which is more cost-effective and
      precludes carriers from being missed, while monitoring the occurrence of S.
      aureus infections caused by mupirocin-resistant strains.

PMID- 29473541
TI  - A kinase-dependent feedforward loop affects CREBB stability and long term memory
      formation.
AB  - In Drosophila, long-term memory (LTM) requires the cAMP-dependent transcription
      factor CREBB, expressed in the mushroom bodies (MB) and phosphorylated by PKA. To
      identify other kinases required for memory formation, we integrated Trojan exons
      encoding T2A-GAL4 into genes encoding putative kinases and selected for genes
      expressed in MB. These lines were screened for learning/memory deficits using UAS
      RNAi knockdown based on an olfactory aversive conditioning assay. We identified a
      novel, conserved kinase, Meng-Po (MP, CG11221, SBK1 in human), the loss of which
      severely affects 3 hr memory and 24 hr LTM, but not learning. Remarkably, memory
      is lost upon removal of the MP protein in adult MB but restored upon its
      reintroduction. Overexpression of MP in MB significantly increases LTM in wild
      type flies showing that MP is a limiting factor for LTM. We show that PKA
      phosphorylates MP and that both proteins synergize in a feedforward loop to
      control CREBB levels and LTM. key words: Drosophila, Mushroom bodies, SBK1,
      deGradFP, T2A-GAL4, MiMIC.

PMID- 29473542
TI  - Facile preparation of a TiO2 quantum dot/graphitic carbon nitride heterojunction
      with highly efficient photocatalytic activity.
AB  - In this article, mechanical grinding, an effortless and super-effective synthetic
      strategy, is used to successfully synthesize a TiO2 quantum dot
      (TiO2QD)/graphitic carbon nitride (g-C3N4) heterostructure. X-ray photoelectron
      spectroscopy results together with transmission electron microscopy reveal the
      formation of the TiO2QD/g-C3N4 heterostructure with strong interfacial
      interaction. Because of the advantages of this characteristic, the prepared
      heterostructure exhibits excellent properties for photocatalytic wastewater
      treatment. Notably, the optimum photocatalytic activity of the TiO2QD/g-C3N4
      heterostructure is nearly 3.4 times higher than that of the g-C3N4 nanosheets
      used for the photodegradation of rhodamine B pollutant. In addition, the
      stability and possible degradation mechanism of the TiO2QD/g-C3N4 heterojunction
      are studied in detail. This method may stimulate an effective approach to
      synthesizing QD-sensitized semiconductor materials and facilitate their
      application in environmental protection.

PMID- 29473543
TI  - Creating virtual electrodes with 2D current steering.
AB  - OBJECTIVE: Current steering techniques have shown promise in retinal prostheses
      as a way to increase the number of distinct percepts elicitable without
      increasing the number of implanted electrodes. Previously, it has been shown that
      'virtual' electrodes can be created between simultaneously stimulated electrode
      pairs, producing unique cortical response patterns. This study investigated
      whether virtual electrodes could be created using 2D current steering, and
      whether these virtual electrodes can produce cortical responses with predictable
      spatial characteristics. APPROACH: Normally-sighted eyes of seven adult
      anaesthetised cats were implanted with a 42-channel electrode array in the
      suprachoroidal space and multi-unit neural activity was recorded from the visual
      cortex. Stimuli were delivered to individual physical electrodes, or electrodes
      grouped into triangular, rectangular, and hexagonal arrangements. Varying
      proportions of charge were applied to each electrode in a group to 'steer'
      current and create virtual electrodes. The centroids of cortical responses to
      stimulation of virtual electrodes were compared to those evoked by stimulation of
      single physical electrodes. MAIN RESULTS: Responses to stimulation of groups of
      up to six electrodes with equal ratios of charge on each electrode resulted in
      cortical activation patterns that were similar to those elicited by the central
      physical electrode (centroids: RM ANOVA on ranks, p  >  0.05; neural spread: one
      way ANOVA on Ranks, p  >  0.05). We were also able to steer the centroid of
      activation towards the direction of any of the electrodes of the group by
      applying a greater charge to that electrode, but the movement in the centroid was
      not found to be significant. SIGNIFICANCE: The results suggest that current
      steering is possible in two dimensions between up to at least six electrodes,
      indicating it may be possible to increase the number of percepts in patients
      without increasing the number of physical electrodes. Being able to reproduce
      spatial characteristics of responses to individual physical electrodes suggests
      that this technique could also be used to compensate for faulty electrodes.

PMID- 29473545
TI  - A celebration: Dr Dan Galeriu 1947-2017 (republication).

PMID- 29473544
TI  - Biokinetic models for Group VB elements.
AB  - This paper reviews biokinetic data for the Group VB elements vanadium, niobium,
      and tantalum, and presents biokinetic models describing their systemic behaviour.
      The model for systemic niobium in adults was developed earlier and described in
      Publication 134 of the International Commission on Radiological Protection. The
      model for niobium is used as a starting point for the development of models for
      vanadium and tantalum. Published biokinetic data for vanadium, including
      comparisons with niobium, indicate that the initial distribution of vanadium is
      broadly similar to that of niobium but that vanadium is less firmly fixed in most
      tissues and is excreted more rapidly than niobium. Biokinetic data for tantalum
      are more limited but suggest that its systemic behaviour closely resembles that
      of niobium at early times after administration. The model for niobium is proposed
      for application to tantalum in view of the suggested biological similarities of
      tantalum and niobium, their generally strong coherence in nature due to similar
      ionic radii and identical valence states, and the difficulties in developing
      parameter values directly from available data for tantalum. The proposed model
      for vanadium relies largely on vanadium-specific information and varies
      considerably from the model for niobium.

PMID- 29473546
TI  - Excellent microwave response derived from the construction of dielectric-loss 1D
      nanostructure.
AB  - Increasing efforts have recently been devoted to the artificial design and
      function of nanostructures for their application prospects in catalysis, drug
      delivery, energy storage, and microwave absorption. With the advantages of
      natural abundance, low cost, and environment friendliness, a one-dimensional (1D)
      MnO2 nanowire (MW) is the representative dielectric-loss absorber for its special
      morphology and crystalline structure. However, its low reflection loss (RL) value
      due to its thin thickness limits its wide development and application in the
      microwave absorption field. In this work, artificially designed MnO2@AIR@C (MCs),
      namely, 1D hollow carbon nanotubes filled with nano-MnO2, were designed and
      synthesized. It is found that the RL value of the MC is almost lower than -10 dB.
      Furthermore, the RL value was able to achieve -18.9 dB with an effective
      bandwidth (-10 dB) of 5.84 GHz at 2.25 mm. Simultaneously, the dielectric and
      interfacial polarization became stronger while the impedance matching was much
      better than in the single MWs. Hence, the rational design and fabrication of
      micro-architecture are essential and MC has great potential to be an outstanding
      microwave absorber.

PMID- 29473547
TI  - Coupling mechanical tension and GTPase signaling to generate cell and tissue
      dynamics.
AB  - Regulators of the actin cytoskeleton such Rho GTPases can modulate forces
      developed in cells by promoting actomyosin contraction. At the same time, through
      mechanosensing, tension is known to affect the activity of Rho GTPases. What
      happens when these effects act in concert? Using a minimal model (1 GTPase
      coupled to a Kelvin-Voigt element), we show that two-way feedback between
      signaling ('RhoA') and mechanical tension (stretching) leads to a spectrum of
      cell behaviors, including contracted or relaxed cells, and cells that oscillate
      between these extremes. When such 'model cells' are connected to one another in a
      row or in a 2D sheet ('epithelium'), we observe waves of contraction/relaxation
      and GTPase activity sweeping through the tissue. The minimal model lends itself
      to full bifurcation analysis, and suggests a mechanism that explains behavior
      observed in the context of development and collective cell behavior.

PMID- 29473548
TI  - Cosmology with the Large Synoptic Survey Telescope: an overview.
AB  - The Large Synoptic Survey Telescope (LSST) is a high etendue imaging facility
      that is being constructed atop Cerro Pachon in northern Chile. It is scheduled to
      begin science operations in 2022. With an [Formula: see text] ([Formula: see
      text] effective) aperture, a novel three-mirror design achieving a seeing-limited
      [Formula: see text] field of view, and a 3.2 gigapixel camera, the LSST has the
      deep-wide-fast imaging capability necessary to carry out an [Formula: see text]
      survey in six passbands (ugrizy) to a coadded depth of [Formula: see text] over
      10 years using [Formula: see text] of its observational time. The remaining
      [Formula: see text] of the time will be devoted to considerably deeper and faster
      time-domain observations and smaller surveys. In total, each patch of the sky in
      the main survey will receive 800 visits allocated across the six passbands with
      [Formula: see text] exposure visits. The huge volume of high-quality LSST data
      will provide a wide range of science opportunities and, in particular, open a new
      era of precision cosmology with unprecedented statistical power and tight control
      of systematic errors. In this review, we give a brief account of the LSST
      cosmology program with an emphasis on dark energy investigations. The LSST will
      address dark energy physics and cosmology in general by exploiting diverse
      precision probes including large-scale structure, weak lensing, type Ia
      supernovae, galaxy clusters, and strong lensing. Combined with the cosmic
      microwave background data, these probes form interlocking tests on the
      cosmological model and the nature of dark energy in the presence of various
      systematics. The LSST data products will be made available to the US and Chilean
      scientific communities and to international partners with no proprietary period.
      Close collaborations with contemporaneous imaging and spectroscopy surveys
      observing at a variety of wavelengths, resolutions, depths, and timescales will
      be a vital part of the LSST science program, which will not only enhance specific
      studies but, more importantly, also allow a more complete understanding of the
      Universe through different windows.

PMID- 29473549
TI  - Stroke prevention in atrial fibrillation: Commentary regarding the AAN's evidence
      based guideline update.

PMID- 29473550
TI  - Osteoporosis for the practicing neurologist.

PMID- 29473551
TI  - Think global, act global.

PMID- 29473552
TI  - Episode-based care for stroke: Can neurologists play a leading role?

PMID- 29473553
TI  - Microbial DNA testing for inflammatory diseases of the brain of uncertain
      etiology.
AB  - Neurologists may be confronted with patients who present with inflammatory brain
      lesions where the diagnosis cannot be made through history and physical
      examination alone. Molecular testing for bacterial infections, tuberculosis, and
      fungal infections may aid in the diagnosis. Since the treatments for these
      disorders are different and delays can result in permanent neurologic disability
      and death, rapid and accurate diagnoses are critical. This review provides the
      neurologist with testing options and recommends ways to enhance sensitivity and
      specificity.

PMID- 29473554
TI  - Multisensory remission of somatoparaphrenic delusion: My hand is back!
AB  - This study investigates whether the rubber hand illusion (RHI) can induce a
      remission of somatoparaphrenia, a somatic delusion usually following right
      hemisphere damage, which typically manifests as a defective sense of ownership of
      one's contralesional body parts. First, we show that patients with
      somatoparaphrenia can experience a reliable RHI, exhibiting illusory effects
      similar to those reported by healthy participants. Moreover, synchronous touches
      applied to the patients' visible disowned left hand (rather than to the rubber
      hand), and to their right invisible unimpaired hand, induce an immediate self
      attribution of the disowned hand, without affecting other sensorimotor or
      attentional disorders. The higher-level representation of the body concerned with
      ownership, deranged as a somatic delusion in patients with somatoparaphrenia, is
      penetrable, and can be restored by multisensory stimulations.

PMID- 29473555
TI  - The menagerie of neurology: Animal signs and the refinement of clinical acumen.
AB  - Neurology is a field known for "eponymophilia." While eponym use has been a
      controversial issue in medicine, animal-related metaphoric descriptions continue
      to flourish in neurologic practice, particularly with the advent of neuroimaging.
      To provide practicing and trainee neurologists with a useful reference for all
      these colorful eponyms, we performed a literature review and summarized the
      various animal eponyms in the practice of neurology (and their etiologic
      implications) to date. We believe that the ability to recognize animal-like
      attributes in clinical neurology and neuroradiology may be attributed to a visual
      phenomenon known as pareidolia. We propose that animal eponyms are a useful
      method of recognizing clinical and radiologic patterns that aid in the diagnostic
      process and therefore are effective aidesmemoire and communicative tools that
      enliven and improve the practice of neurology.

PMID- 29473556
TI  - Sleep medicine practice adaptations.

PMID- 29473557
TI  - Unrecognized cobalamin deficiency, nitrous oxide, and reversible subacute
      combined degeneration.

PMID- 29473558
TI  - Unrecognized cobalamin deficiency, nitrous oxide, and reversible subacute
      combined degeneration.

PMID- 29473560
TI  - Postmarketing adverse drug reactions: A duty to report?

PMID- 29473559
TI  - Diagnostic and therapeutic spinal interventions: Facet joint interventions.
AB  - Axial spine pain is a common condition that is due to facet joint disease in some
      patients. Local anesthetic blocks of the medial branches of the dorsal rami of
      the spinal nerves that innervate facet joints are used to identify painful facet
      joints. Subsequent radiofrequency neurotomy of the medial branches serving
      symptomatic facet joints may provide prolonged albeit impermanent pain relief.
      The diagnostic blocks and radiofrequency treatments are best validated in the
      cervical spine. Neurologists should be aware that patients with axial spine pain
      who are referred to a pain clinic or pain management facility are likely to be
      considered for diagnostic and therapeutic interventions directed at facet joints
      and their sensory nerve supply.

PMID- 29473561
TI  - Current controversies: Physicians vs Pharma.

PMID- 29473562
TI  - Diagnostic and therapeutic spinal interventions: Diskography.
AB  - Diskography (provocation diskography, disk stimulation) is an invasive diagnostic
      test performed to confirm or exclude internal disk disruption as the cause of
      axial spine pain. Diskography involves injecting fluid into the nucleus of the
      disk under manometric control; a positive response is reproduction of typical
      pain. Extensive but indirect literature validates diskography in the lumbar
      spine; it is less well-supported in the cervical or thoracic spine. Risks include
      rare instances of infection and neural injury; lumbar diskography may be
      associated with accelerated disk degeneration. Diskography has utility in
      establishing a diagnosis of diskogenic pain. When negative, it prevents
      inappropriate interventions directed at the disk; when positive, it prevents
      interventions directed at other axial pain generators. Its role in selecting
      patients for therapies directed at diskogenic pain is limited by the lack of
      available validated treatments.

PMID- 29473563
TI  - Are randomized, blind clinical trials enough to guide individualized decisions
      for patients with neurologic diseases?
AB  - The practice of medicine relies on the patient-physician relationship, knowledge,
      and clinical judgment. Randomized controlled trials (RCTs) remain the least
      biased method for studying the effects of interventions in selected populations
      and are the only method to control adequately for unknown confounders. However,
      physicians face the limitations of RCTs on a daily basis as they treat relatively
      unselected populations and individual patients. We explore the benefits and
      limitations of RCTs for some neurologic disorders, and discuss the difficulties
      of predicting individualized outcomes and anticipating treatment responses in
      those heterogeneous conditions. Observational studies and advances in
      understanding neurologic diseases complement RCTs in decision-making.
      Considerable challenges remain for personalized medicine; for now, clinicians
      must rely on their ability to integrate evidence and clinical judgment.

PMID- 29473564
TI  - Diagnostic and therapeutic spinal interventions: Epidural injections.
AB  - Epidural injections of local anesthetic or a corticosteroid are frequently given
      to diagnose and treat patients with radicular pain originating from any spinal
      level. The best-quality evidence supports a transforaminal approach in the lumbar
      spine. Many patients experience substantial benefit from a single therapeutic
      injection. Depending upon the benefit obtained, additional injections may be
      administered. Selective nerve blocks with local anesthetic alone can identify the
      spinal nerve mediating the patient's pain. Serious short-term risks are rare but
      occur; long-term risks are infrequent and can be due to systemic effects of
      multiple corticosteroid injections. Patients who have failed conservative therapy
      or are not candidates for surgical intervention can be considered for epidural
      steroid injections to relieve their radicular pain temporarily.

PMID- 29473565
TI  - Should I offer vagus nerve stimulation as part of my neurology practice?
AB  - Vagus nerve stimulation (VNS) is a safe and effective adjunctive therapy approved
      for patients with partial-onset seizures. A pulse generator, which is implanted
      in the chest wall, delivers programmed electrical pulses through an electrode
      that is attached to the left vagus nerve. VNS plays an important role in the
      treatment of patients with drug-resistant epilepsy. It is currently offered in
      academic as well as private practice settings. After a comprehensive workup is
      performed, VNS should be offered to patients with drug-resistant epilepsy who are
      not candidates for surgery.

PMID- 29473566
TI  - MRI pattern approach of adult-onset inherited leukoencephalopathies.
AB  - White matter hyperintensities are frequently encountered in clinical practice. In
      adulthood, white matter hyperintensities are generally related to acquired
      disorders, such as vascular, inflammatory, or demyelinating diseases. Symmetrical
      and confluent white matter abnormalities on the first available MRI suggest a
      genetic disorder. In this article, we provide keys to recognize and classify the
      adult-onset forms of inherited leukoencephalopathies and to identify their causes
      by targeting specific biochemical or molecular biomarkers.

PMID- 29473568
TI  - Neuroinfectious disease: A rapidly evolving challenge.

PMID- 29473567
TI  - Management of sleep apnea in the neurology patient: Five new things.
AB  - Recognizing and treating sleep-disordered breathing (SDB) is essential in
      delivering neurologic care due to its association with a growing list of
      neurologic conditions (e.g., stroke, neurodegenerative disorders). Thus,
      increased proficiency in the recognition and management of SDB is likely to
      result in better outcomes, care, and utilization of health care resources. To
      date, continuous positive airway pressure remains the gold standard for patients
      with moderate to severe obstructive sleep apnea and has been shown to be
      effective in treating variations of SDB. Appropriate application of new methods
      and technology such as home sleep testing can help bridge the gap between the
      need and supply for sleep health care and delivery. Increased focus on
      efficacious strategies to further awareness and education for patients,
      caretakers, and providers is paramount to long-term adherence to treatment.

PMID- 29473569
TI  - Health literacy and medication awareness in outpatient neurology.

PMID- 29473570
TI  - Episode-based payment for ischemic stroke care with implications for
      neurologists.
AB  - Episode-based payment bundles a single lumped payment around a health care event,
      such as ischemic stroke. Hospitals are already experienced with a type of episode
      based payment for stroke, the diagnosis-related group payment system. Ischemic
      stroke fits well into an episode-based system because (1) ischemic stroke is
      common, (2) an ischemic stroke care episode lasts for a definable period of time,
      and (3) ischemic stroke care costs are high and episode-based payment could
      provide savings. In an episode-based ischemic stroke care payment system built
      around cost savings, it is unclear whether neurologists would provide savings.
      Neurologists need to prove, and define, the value they bring to ischemic stroke
      care.

PMID- 29473571
TI  - An elusive brain death diagnosis: You can't get there from here.

PMID- 29473573
TI  - Anterior spinal artery infarction causing man-in-the-barrel syndrome.

PMID- 29473572
TI  - Late-onset ataxia telangiectasia.

PMID- 29473574
TI  - Weighing the risks and benefits of intervention.

PMID- 29473575
TI  - Medical legal consultation in neurologic practice.
AB  - Responding to requests from attorneys concerning patients or providing
      independent consultations in the legal process may present unique challenges,
      particularly if special reports are needed or if there is to be testimony under
      oath. While the legal process is adversarial, the role of the physician
      consultant, whether acting as treating physician or independent expert, is not to
      advocate for one side or the other, or to persuade the trier of fact, but to
      state his or her professional opinion clearly and concisely. The American Academy
      of Neurology published a position statement on "Qualifications and Guidelines for
      the Physician Expert Witness" in 2005. Following professional practice guidelines
      allows the neurologist to participate in the legal process effectively and
      ethically. The larger the pool of neurologists available for consultation in
      legal matters, the more access the legal system will have to balanced expertise.

PMID- 29473576
TI  - Diffusion-weighted imaging in a case of malignant optic glioma.

PMID- 29473577
TI  - Cerebral varicella-zoster vasculopathy sine herpete: Atypical Ramsay-Hunt
      syndrome in an immunocompetent patient.

PMID- 29473578
TI  - Neuroimaging of first-ever seizure: Contribution of MRI if CT is normal.

PMID- 29473579
TI  - Spinal pain: When is it time for an intervention?

PMID- 29473580
TI  - Sleep disorders in clinical practice: A wake-up call for neurologists.

PMID- 29473581
TI  - Treatment considerations of cervical spondylotic myelopathy.
AB  - Cervical spondylotic myelopathy (CSM) is the leading cause of myelopathy in
      patients over age 50 years. Despite advances, CSM remains a clinical diagnosis
      and its natural history remains unclear. The treatment of CSM is controversial,
      especially in patients with mild or moderate clinical disease without rapid
      progression of symptoms. Herein, we begin with a clinical vignette followed by a
      brief description of the clinical problems. We discuss evaluation, treatment, and
      recommendations for the treatment of CSM. Emphasis is drawn to areas of
      uncertainty and present level of evidence for the treatment modalities of CSM.

PMID- 29473582
TI  - Utility of sleep studies in neurologic practice.
AB  - Sleep disorders are frequent in patients with neurologic disease. This article
      provides an approach to the patient with sleep complaints that can be implemented
      during the course of a neurologic evaluation. Recognition of a sleep complaint is
      the key that leads to use of appropriate scales and sleep diaries to form a
      differential sleep diagnosis. Choosing the correct sleep test is essential to
      confirm diagnosis and plan therapy. We describe the important sleep tests for
      practicing neurologists: polysomnography, multiple sleep latency test, and
      maintenance of wakefulness test, as well as actigraphy and oximetry. The approved
      use of limited channel home tests (also known as "out of center testing," or
      "portable monitoring") is reviewed and an algorithm provided to guide the
      approach to the sleepy patient.

PMID- 29473583
TI  - Transient disappearance of white matter lesions on correction of hyponatremia.

PMID- 29473584
TI  - Cost-effectiveness data: Are neurologists in practice equipped to interpret them?

PMID- 29473585
TI  - HIV-associated dementia: Prompt response to zidovudine.

PMID- 29473586
TI  - Approach to insomnia in patients with dementia.
AB  - Insomnia occurs in one-fourth to one-third of patients with dementia, and can
      lead to patient and caretaker distress and early institutionalization. An array
      of effects from the disease, medication, behaviors, and mood issues may play a
      role in influencing sleep. This perplexing issue can be handled effectively with
      appropriate evaluation and understanding of basic sleep-wake physiology. For most
      patients, appropriate timing of cues, modifying behavior, and optimizing
      medications can improve the patient's and caregiver's quality of life. In this
      article, we review signs that may help the clinician recognize insomnia early and
      approach the issue in a logical manner.

PMID- 29473587
TI  - Sleep medicine practice adaptations.
AB  - Sleep medicine has been a rapidly growing field for the last 15 years. Medicare
      and private payer insurers continually examine testing and treatment closely to
      monitor potential fraudulent practices. In this article, we explore responses by
      some practitioners to adapt to policy changes. In addition, we offer advice to
      clinicians on how to review their customary office procedures and involve
      patients in overcoming administrative obstacles to the diagnostic and therapeutic
      course agreed upon by a doctor and patient.

PMID- 29473588
TI  - Diagnosis and management of periodic hypothermia.
AB  - Hypothermia, defined as a core temperature below 35 degrees C, can occur in a
      variety of clinical settings, including environmental exposure, shock, infection,
      metabolic disorders (such as hypothyroidism, adrenal insufficiency, and Wernicke
      encephalopathy), malnutrition, and alcohol or drug toxicity. Typically,
      hypothermia should resolve with treatment of the underlying disorder. However, in
      rare cases patients experience recurrent episodes of hypothermia in the context
      of a stereotyped syndrome due to a hypothalamic lesion, which can be either
      congenital or acquired. The episodes are characterized by progressive confusion
      and a decreased level of arousal, hypothermia, and eventual resolution with a
      return to baseline. Additional clinical findings during episodes may include
      diaphoresis, asterixis, bradycardia, and thrombocytopenia. These recurrent
      episodes represent periodic hypothermia.

PMID- 29473589
TI  - Benign MRI findings and their pathologic mimics.
AB  - Otherwise benign MRI findings (so-called "incidentalomas") are a frequent cause
      of worry on the part of both clinician and patient. Knowledge of the imaging
      characteristics of incidentalomas, their (typically slight) pathologic
      significance, and how to distinguish these from less benign pathologic mimics can
      help avoid unnecessary worry, expense, and workup.

PMID- 29473591
TI  - Stop losing sleep over sleep.

PMID- 29473590
TI  - Generic substitution of antiepileptic drugs: What's a clinician to do?

PMID- 29473592
TI  - Standard strategies for diagnosis and treatment of patients with newly diagnosed
      Parkinson disease.

PMID- 29473593
TI  - Practice across borders: What is the standard approach to assessment of an
      unprovoked seizure in an adult?

PMID- 29473594
TI  - Vagus nerve stimulation in the treatment of epilepsy: Payment policy
      perspectives.
AB  - This article is presented as a companion to the recent American Academy of
      Neurology (AAN) guideline update on use of vagus nerve stimulation (VNS) for
      treating epilepsy. The guideline update reaffirms the efficacy of VNS for
      intractable epilepsy. Whereas it upholds the value of VNS for its originally
      approved indications, the guideline reminds us of existing evidence gaps and
      unmet research needs. This companion identifies ambiguities in the definition of
      intractable epilepsies and discusses the use of VNS in children under age 12
      years and in persons with intellectual disabilities (mental retardation). Many
      payers require prior authorization and fulfillment of criteria for coverage of
      VNS. This article provides guidance and background information to reduce
      obstacles for coverage, especially where uncertainties exist and levels of
      evidence are lower.

PMID- 29473595
TI  - Neurologists and technology: The changing "Facebook" of practice.
AB  - Social and traditional media are revolutionizing health care. Medicine, once an
      art practiced behind closed doors, is now part of the public domain. This article
      will help neurologists navigate a complex maze of technology to optimize patient
      care without compromising privacy. We offer ideas for improving our digital
      "footprint." Guidance is given on maintaining professional demeanor in all
      private and public interactions to help us avoid personal or patient insult and
      injury. Acknowledging that neurology is becoming a specialty of increased
      personal and social education, we outline ways to proactively improve our patient
      care and education locally and globally.

PMID- 29473596
TI  - Rapid onset and termination of neuroimaging findings in intracranial hypotension.

PMID- 29473597
TI  - Erratum: Contraindications to intravenous rtPA for acute stroke: A critical
      reappraisal.
AB  - [This corrects the article on p. 177 in vol. 3.].

PMID- 29473598
TI  - A case of celiac disease with hallucinations.

PMID- 29473599
TI  - How to select and implement an electronic health record in a neurology practice.
AB  - The purchase, implementation, and maintenance of an electronic health record
      (EHR) are among the most significant financial investments a practice will make.
      A practice's choice of EHR will have long-term and wide-ranging implications for
      how that practice operates. A successful EHR implementation may potentially
      result in increased efficiency, improved quality of patient care, and a possibly
      more successful practice. Extensive research and thoughtful planning, done with
      the involvement of all stakeholders, the commitment of adequate time, staff, and
      financial resources to the process, and sufficient training will increase the
      chances for a successful EHR implementation.

PMID- 29473600
TI  - Osteoporosis for the practicing neurologist.
AB  - Osteoporosis is a common condition of impaired bone strength leading to
      fractures. A targeted history, physical exam, and blood work can help elucidate
      potentially reversible causes of low bone mass. In the neurology office,
      particular attention should be paid to the patient on glucocorticoids or
      antiepileptic medications, as these have distinct detrimental effects on bone.
      Patients can be risk-stratified by using the FRAX calculator, a tool that can
      help determine whether the patient is at sufficient risk of fracture to warrant
      pharmacologic therapy. Nonpharmacologic treatments such as calcium, vitamin D,
      and exercise should be discussed with the patient. The cornerstone of
      pharmacologic therapy has been treatment with bisphosphonates, but newer
      medications are available as well for the high-risk patient.

PMID- 29473601
TI  - Emerging devices for epilepsy.
AB  - About 30% of people with epilepsy continue to have seizures despite a growing
      array of antiseizure drugs. For some of these people, surgical resection of brain
      tissue is an effective therapeutic option. For others, the likelihood of seizure
      freedom is low, and has not improved much despite the introduction of several new
      antiseizure drugs. The vagus nerve stimulator is the only device approved by the
      Food and Drug Administration (FDA), but it rarely results in freedom from
      seizures. Recently, 2 approaches to electrical stimulation of the brain have been
      reported. One device has been approved for use in Canada and in Europe, and it
      seems likely that one or more such devices will be approved for use in the United
      States. We examine some of the data from these studies in the context of the
      current FDA-approved drugs and devices.

PMID- 29473602
TI  - A 16-year-old transplant patient with amnesia, insomnia, and visual
      hallucinations.

PMID- 29473603
TI  - EMG/NCV in the evaluation of spine trauma with radicular symptoms.

PMID- 29473604
TI  - Neuroimaging of first-ever seizure: Contribution of MRI if CT is normal.
AB  - The role of neuroimaging in the assessment of a first-ever seizure has not been
      well-defined, in particular the utility of MRI when CT is normal. The results of
      neuroimaging (CT brain, MRI brain, or both) in 1,013 adults with first-ever
      unprovoked seizure were correlated with clinical features and seizure outcome.
      Epileptogenic lesions were identified in 29%. Of patients with a normal CT who
      also had MRI, 12% had an epileptogenic lesion on MRI, the strongest independent
      predictor of which was a focal abnormality on EEG. Patients with an epileptogenic
      lesion had a higher risk of seizure recurrence, including when this was only
      evident on MRI.

PMID- 29473605
TI  - Rare and treatable cause of progressive visual loss.

PMID- 29473606
TI  - Homonymous hemianopia in nonketotic hyperglycemia is an ictal phenomenon.
AB  - Extended video-EEG or 18F-fluorodeoxyglucose PET (FDG-PET) was obtained in 3
      adult patients with hemianopia secondary to nonketotic hyperglycemia. Two male
      patients presented with left hemianopia and episodic left gaze deviation and one
      male patient presented with right hemianopia and visual hallucinations. None of
      the 3 patients had a history of seizures or known epilepsy risk factors. All 3
      patients were found to have elevated serum glucose (267 mg/dL, 320 mg/dL, and 487
      mg/dL) without acidosis or urine ketones. In all 3 patients, video-EEG recorded
      recurrent ictal discharges originating from the posterior quadrant contralateral
      to their hemianopia. In 2 patients, FDG-PET demonstrated corresponding focal
      areas of hypermetabolism. Resolution of visual symptoms was achieved with
      antiepileptic drugs, hydration, and tight glycemic control.

PMID- 29473607
TI  - Simultaneous PML-IRIS and myelitis in a patient with neuromyelitis optica
      spectrum disorder.

PMID- 29473608
TI  - Bilateral thalamic glioma.

PMID- 29473609
TI  - The revolution of practice.

PMID- 29473610
TI  - Limbic encephalitis as the presenting feature of Sjogren syndrome.

PMID- 29473611
TI  - Highlights of the issue.

PMID- 29473612
TI  - Intravenous immunoglobulin for treatment of neuromuscular disease.
AB  - Intravenous immunoglobulin (IVIg) has been widely used in the treatment of
      autoimmune neuromuscular diseases. Compared to other treatment modalities, such
      as corticosteroids and chemotherapy for autoimmune disorders, IVIg has relatively
      few side effects and favorable therapeutic outcomes in certain neuromuscular
      diseases. There is Class I evidence for IVIg as an initial treatment for patients
      with Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating
      polyneuropathy (CIDP), and multifocal motor neuropathy. It is as effective as
      plasma exchange in GBS and CIDP. In myasthenia gravis, IVIg is used for
      myasthenic crisis and exacerbations, though it is also helpful as maintenance
      therapy, particularly in patients with a suboptimal response or contraindications
      to prednisone or other immunosuppressive agents. IVIg has been demonstrated to be
      beneficial in placebo-controlled, double-blind, randomized studies in
      dermatomyositis and Lambert-Eaton syndrome. IVIg has also been beneficial in
      select patients with polymyositis and other autoimmune peripheral neuropathies.
      Clinical trials in amyotrophic lateral sclerosis, inclusion body myositis, and
      anti-myelin-associated glycoprotein neuropathy have been negative.

PMID- 29473613
TI  - Neurologic complications of anesthesia: A practical approach.
AB  - Neurologic complications related to anesthesia are infrequent but can be serious.
      Neurologists are often consulted to evaluate patients with postoperative symptoms
      and must be ready to discriminate those truly caused by the anesthetic drug or
      procedure from the more common postoperative complications that are unrelated to
      the anesthesia itself. This practical review relies on cases to illustrate common
      reasons for neurologic consultation in the postsurgical setting. It also briefly
      summarizes what to expect when patients with central or peripheral neurologic
      disease undergo surgery under general or regional anesthesia.

PMID- 29473614
TI  - Standard strategies for acute ischemic stroke within the rtPA therapeutic window:
      Australia.

PMID- 29473615
TI  - FTD with catatonia-like signs that temporarily resolved with zolpidem.

PMID- 29473616
TI  - It's about the money.

PMID- 29473617
TI  - Standard strategies for acute ischemic stroke within the rtPA therapeutic window.

PMID- 29473618
TI  - Pediatric sleep apnea: Five things you might not know.
AB  - Obstructive sleep apnea is a frequently overlooked, treatable disorder that is
      common among children. This article discusses 5 important aspects of this
      disorder that might not be known to the general pediatric practitioner or
      pediatric neurologist. These aspects are important in screening, properly
      evaluating, and treating children with obstructive sleep apnea.

PMID- 29473619
TI  - Erratum: Multiple sclerosis: Five new things.
AB  - [This corrects the article on p. 404 in vol. 3, PMID: 24175156.].

PMID- 29473620
TI  - Extensive spinal epidural CSF collection after lumbar puncture.

PMID- 29473621
TI  - Alien hand phenomenon in right anterior cerebral artery infarct.

PMID- 29473622
TI  - Changes in emergency department coverage for the neurologist.
AB  - The role of the neurologist in the emergency department (ED) is constantly
      evolving and has become more diversified in recent times. This article gives an
      overview of different practice models that neurologists are employing to cover ED
      calls. A review of billing and coding for ED visits is also discussed.

PMID- 29473623
TI  - Bilateral cervical internal carotid artery dissections in Eagle syndrome.

PMID- 29473624
TI  - Sports-related concussion: Truth be told.

PMID- 29473625
TI  - Enhancing the quality of care for patients with multiple sclerosis through
      performance improvement CME.
AB  - Multiple sclerosis (MS) is an inflammatory neurodegenerative disease marked by a
      heterogeneous clinical presentation and disease course. Although improvements in
      the recognition and management of MS have been made in recent years, challenges
      remain due to the complex nature of the disease. Clinicians must remain current
      with their skills as knowledge surrounding MS care continues to advance. Here we
      report results of a performance improvement (PI) continuing medical education
      (CME) activity that was designed to promote evidence-based care of patients with
      MS. Participants demonstrated significant improvements in assessing disease
      related complications, treating cognitive dysfunction, assessing adherence, and
      providing disease-related educational materials. These data support the role of
      PI CME in improving clinician practices that align with quality MS patient care.

PMID- 29473626
TI  - Standard strategies for acute ischemic stroke within the rtPA therapeutic window:
      China.

PMID- 29473627
TI  - A rare case of cerebral proliferative angiopathy with bihemispheric morphology.

PMID- 29473628
TI  - Recovery audits: Practical update for neurology practices.
AB  - Recovery Audit Contractors (RACs) are contracted by the federal government to
      review providers' medical billing. Experience has demonstrated substantial
      savings to the strapped Medicare fund, fueling increased scrutiny. RAC audits are
      constrained to published focus areas, and its targeted approach makes use of
      sophisticated analytics. Although some of the analyses used by the RACs may be
      proprietary, much of the auditing process is transparent, allowing providers to
      prepare their practices in advance of audits. This article reviews the current
      state of RAC auditing and offers strategies to minimize financial pain and
      leverage the process for competitive advantage.

PMID- 29473629
TI  - Neurologic diseases in women: Five new things.
AB  - This review highlights some of the new epidemiologic information concerning sex
      differences involving combined oral contraceptives and stroke, depression and
      selective serotonin reuptake inhibitors use during pregnancy, emerging knowledge
      of the teratogenicity and cognitive effects of anticonvulsants during pregnancy,
      demyelinating disorders in pregnancy, and the influence of timing of hormonal
      exposure on the risk of Alzheimer disease.

PMID- 29473630
TI  - Standard strategies for acute ischemic stroke within the rtPA therapeutic window:
      Egypt.

PMID- 29473631
TI  - Dimethyl fumarate for relapsing MS.
AB  - Dimethyl fumarate (DMF) is the latest oral therapy approved for relapsing
      remitting multiple sclerosis (RRMS). In 2 placebo-controlled phase III trials,
      twice daily DMF demonstrated a 44%-53% reduction in annualized relapse rate and
      71%-90% reduction in new MRI lesions. In one trial, DMF slowed the accumulation
      of disability, but not in the other trial. The main side effects of DMF include
      gastrointestinal symptoms (nausea, abdominal pain, vomiting, and diarrhea) and
      skin flushing, which peak at treatment initiation. There was no increased risk of
      opportunistic infections. Recommended safety monitoring includes complete blood
      count prior to treatment and annually while on treatment. Appealing aspects of
      DMF include potent efficacy, oral administration, and good safety and
      tolerability profiles. Altogether, DMF is an attractive option for first-line
      treatment, breakthrough disease activity, intolerance to other therapies, and
      possibly natalizumab-treated patients with positive JC virus serology.

PMID- 29473632
TI  - Capturing incentives and avoiding penalties: The carrot and the stick.
AB  - Over the past decade, health care in the United States has been a topic of
      intense political debate, resulting in dramatic legislative, regulatory, and
      economic changes. These changes have occurred due to the unsustainable rise of
      health care costs without accompanying improvement in measured health outcomes
      when compared to other economically developed countries. In an attempt to contain
      costs and improve the quality of health care provided, the Center for Medicare
      and Medicaid Services has implemented 4 distinct incentive-based programs. Data
      are scarce concerning whether such programs will be successful in accomplishing
      these goals. Each health care provider will need to weigh the costs of
      participation against the fines incurred by nonparticipation (up to 10% of annual
      Medicare payments). Knowledge of the percentage of one's practice dedicated to
      the care of patients in the Medicare and Medicaid programs will be helpful in
      arriving at a final decision.

PMID- 29473633
TI  - Erratum: Teriflunomide.
AB  - [This corrects the article on p. 254 in vol. 3, PMID: 23914327.].

PMID- 29473634
TI  - Stroke syndromes associated with DWI-negative MRI include ataxic hemiparesis and
      isolated internuclear ophthalmoplegia.
AB  - We present a case series of clinically definite acute stroke with negative
      diffusion-weighted imaging (DWI). This study retrospectively examined a large
      population of stroke patients with the aim of identifying which stroke syndromes
      were more likely to be negative on MRI. Patient records and images were reviewed
      in order to confirm clinically definite stroke and DWI negativity. A total of 701
      patients had MRI during the study period. A total of 16 patients with DWI
      negative MRI and clinically definite stroke as diagnosed by experienced stroke
      consultants were identified. A total of 15 of the 16 cases were classified as
      either posterior circulation or lacunar strokes, and the most common syndromes
      were ataxic hemiparesis and isolated internuclear ophthalmoplegia.

PMID- 29473635
TI  - Standard strategies for acute ischemic stroke within the rtPA therapeutic window:
      Finland.

PMID- 29473636
TI  - Corrigendum to: Nurses' knowledge on phlebotomy in tertiary hospitals in China: a
      cross-sectional multicentric survey.
AB  - [This corrects the article DOI: 10.11613/BM.2018.010703.].

PMID- 29473638
TI  - Stroke: Timing isn't everything.

PMID- 29473637
TI  - Standard strategies for acute ischemic stroke within the rtPA therapeutic window:
      UNITED STATES.

PMID- 29473639
TI  - Practice and payment trends in neurology in 2012.
AB  - This article describes practice and payment trends among neurologists. Data from
      the 2012 Practice and Payment Trends survey were compared to results from the
      2010 Medical Economics survey. Both surveys were sent to a random sample of 1,000
      US practicing neurologists, with a response rate of 32%. Since 2010, there has
      been an 8% increase in the percent of neurologists working in academic medical
      centers. Nearly half of neurologists reported working for a hospital-affiliated
      practice. Wait times have increased 40% for a new patient visit. Only 19% of
      neurologists indicated procedures as the primary focus of their practice. New
      delivery models have not yet gained traction with neurologists but the majority
      (>80%) of neurologists currently use electronic health records in their practice.

PMID- 29473640
TI  - Radiographic evolution of a rapidly reversible leukoencephalopathy due to
      metronidazole.

PMID- 29473641
TI  - Standard strategies for acute ischemic stroke within the rtPA therapeutic window:
      Brazil.

PMID- 29473642
TI  - Contraindications to intravenous rtPA for acute stroke: A critical reappraisal.
AB  - Only 1%-5% of patients with acute ischemic stroke presenting within 3 hours of
      symptoms receive IV recombinant tissue plasminogen activator (rtPA)-the only
      effective treatment available. The administration of rtPA is limited by extensive
      exclusion criteria, many of which are not based on evidence, but rather derived
      from expert opinion for large stroke trials. Over the past 15 years, experiences
      with the use of rtPA in clinical practice have led to evidence suggesting that
      several of the current contraindications for rtPA are unnecessary and overly
      restrictive. In this review, we analyze the evidence-most of which is derived
      from observational research-supporting or contradicting current contraindications
      for administering IV rtPA to acute ischemic stroke patients.

PMID- 29473643
TI  - Formularies, costs, and quality of care.

PMID- 29473645
TI  - Locomotor activity, growth hormones, and systemic robusticity: An investigation
      of cranial vault thickness in mouse lines bred for high endurance running.
AB  - OBJECTIVES: To use a mouse model to investigate the relationships among the
      components of the systemic robusticity hypothesis (SRH): voluntary exercise on
      wheels, spontaneous physical activity (SPA) in cages, growth hormones, and
      skeletal robusticity, especially cranial vault thickness (CVT). MATERIALS AND
      METHODS: Fifty female mice from lines artificially selected for high running (HR)
      and 50 from nonselected control (C) lines were housed in cages with (Active) or
      without wheels (Sedentary). Wheel running and SPA were monitored daily. The
      experiment began at 24-27 days of age and lasted 12 weeks. Food consumption was
      measured weekly. Mice were skeletonized and their interparietal, parietal,
      humerus, and femur were uCT scanned. Mean total thickness of the parietal and
      interparietal bones was determined, along with thickness of the cortical and
      diploe layers individually. Geometric cross-sectional indicators of strength were
      calculated for the long bones. Blood samples were assayed for IGF-1 and IGFBP-3.
      RESULTS: Physical activity differed significantly among groups, based both on
      linetype (C vs. HR) and activity (A vs. S). However, contrary to our predictions,
      the ratio of IGF-1 to IGFBP-3 was higher in C mice than in HR mice. Neither CVT
      nor postcranial robusticity was affected by linetype or activity, nor were most
      measures of CVT and postcranial robusticity significantly associated with one
      another. DISCUSSION: Our results fail to provide support for the systemic
      robusticity hypothesis, suggesting it is important to rethink the long-standing
      theory that increased CVT in Homo erectus reflects increased physical activity
      compared other hominin species.

PMID- 29473644
TI  - The Atrial Fibrillation Health Literacy Information Technology System: Pilot
      Assessment.
AB  - Background: Atrial fibrillation (AF) is a highly prevalent heart rhythm condition
      that has significant associated morbidity and requires chronic treatment. Mobile
      health (mHealth) technologies have the potential to enhance multiple aspects of
      AF care, including education, monitoring of symptoms, and encouraging and
      tracking medication adherence. We have previously implemented and tested
      relational agents to improve outcomes in chronic disease and sought to develop a
      smartphone-based relational agent for improving patient-centered outcomes in AF.
      Objective: The objective of this study was to pilot a smartphone-based relational
      agent as preparation for a randomized clinical trial, the Atrial Fibrillation
      Health Literacy Information Technology Trial (AF-LITT). Methods: We developed the
      relational agent for use by a smartphone consistent with our prior approaches. We
      programmed the relational agent as a computer-animated agent to simulate a face
      to-face conversation and to serve as a health counselor or coach specific to AF.
      Relational agent's dialogue content, informed by a review of literature, focused
      on patient-centered domains and qualitative interviews with patients with AF,
      encompassed AF education, common symptoms, adherence challenges, and patient
      activation. We established that the content was accessible to individuals with
      limited health or computer literacy. Relational agent content coordinated with
      use of the smartphone AliveCor Kardia heart rate and rhythm monitor. Participants
      (N=31) were recruited as a convenience cohort from ambulatory clinical sites and
      instructed to use the relational agent and Kardia for 30 days. We collected
      demographic, social, and clinical characteristics and conducted baseline and 30
      day assessments of health-related quality of life (HRQoL) with the Atrial
      Fibrillation Effect on Quality of life (AFEQT) measure; self-reported medication
      adherence with the Morisky 8-item Medication Adherence Scale (MMAS-8); and
      patient activation with the Patient Activation Measure (PAM). Results:
      Participants (mean age 68 [SD 11]; 39% [12/31] women) used the relational agent
      for an average 17.8 (SD 10.0) days. The mean number of independent log-ins was
      19.6 (SD 10.7), with a median of 20 times over 30 days. The mean number of Kardia
      uses was 26.5 (SD 5.9), and participants using Kardia were in AF for 14.3 (SD
      11.0) days. AFEQT scores improved significantly from 64.5 (SD 22.9) at baseline
      to 76.3 (SD 19.4) units at 30 days (P<.01). We observed marginal but
      statistically significant improvement in self-reported medication adherence
      (baseline: 7.3 [SD 0.9], 30 days: 7.7 [SD 0.5]; P=.01). Assessments of
      acceptability identified that most of the participants found the relational agent
      useful, informative, and trustworthy. Conclusions: We piloted a 30-day smartphone
      based intervention that combined a relational agent with dedicated content for AF
      alongside Kardia heart rate and rhythm monitoring. Pilot participants had
      favorable improvements in HRQoL and self-reported medication adherence, as well
      as positive responses to the intervention. These data will guide a larger,
      enhanced randomized trial implementing the smartphone relational agent and the
      Kardia monitor system.

PMID- 29473647
TI  - Potential virulence factors of bacteria associated with tail fan necrosis in the
      spiny lobster, Jasus edwardsii.
AB  - Tail fan necrosis (TFN) is a common condition found in commercially exploited
      spiny lobsters that greatly diminishes their commercial value. Bacteria
      possessing proteolytic, chitinolytic and lipolytic capabilities were associated
      with TFN in spiny lobsters, Jasus edwardsii. In this study, 69 bacterial isolates
      exhibiting all the three enzymatic capabilities from the haemolymph and tail fans
      of J. edwardsii with and without TFN were further characterized and compared,
      including morphology, biofilm formation, antimicrobial activity, antimicrobial
      resistance, and production of siderophores, melanin and ammonia. The genomic
      patterns of the most common Vibrio crassostreae isolates were also compared
      between TFN-affected and unaffected lobsters. Biofilm formation was stronger in
      bacterial isolates from both haemolymph and tail fans of TFN-affected lobsters
      compared to those from the unaffected lobsters, while melanin production and
      siderophore production were stronger in the isolates from tail fans of lobsters
      with TFN. By contrast, the other characteristics of isolates were similar in
      lobsters with and without TFN. The Vib. crassostreae isolates from the affected
      lobsters had similar genomic patterns. Overall, the results indicate that in
      addition to proteolytic, chitinolytic and lipolytic activities, the bacteria
      associated with TFN commonly have enhanced activity of important virulence
      factors, including biofilm formation, melanin production and siderophore
      production.

PMID- 29473648
TI  - A case of prenatal isolated talipes and 22q11.2 deletion syndrome-an important
      chromosomal disorder missed by noninvasive prenatal screening.

PMID- 29473646
TI  - Research Review: Intergenerational transmission of disadvantage: epigenetics and
      parents' childhoods as the first exposure.
AB  - BACKGROUND: For decades, economists and sociologists have documented
      intergenerational transmission of socioeconomic disadvantage, demonstrating that
      economic, political, and social factors contribute to 'inherited hardship'.
      Drawing on biological factors, the developmental origins of adult health and
      disease model posits that fetal exposure to maternal prenatal distress associated
      with socioeconomic disadvantage compromises offspring's neurodevelopment,
      affecting short- and long-term physical and mental health, and thereby
      psychosocial standing and resources. Increasing evidence suggests that mother-to
      child influence occurs prenatally, in part via maternal and offspring atypical
      HPA axis regulation, with negative effects on the maturation of prefrontal and
      subcortical neural circuits in the offspring. However, even this in utero
      timeframe may be insufficient to understand biological aspects of the
      transmission of factors contributing to disadvantage across generations. METHODS:
      We review animal studies and emerging human research indicating that parents'
      childhood experiences may transfer epigenetic marks that could impact the
      development of their offspring independently of and in interaction with their
      offspring's perinatal and early childhood direct exposures to stress stemming
      from socioeconomic disadvantage and adversity. RESULTS: Animal models point to
      epigenetic mechanisms by which traits that could contribute to disadvantage may
      be transmitted across generations. However, epigenetic pathways of parental
      childhood experiences influencing child outcomes in the next generation are only
      beginning to be studied in humans. With a focus on translational research, we
      point to design features and methodological considerations for human cohort
      studies to be able to test the intergenerational transmission hypothesis, and we
      illustrate this with existing longitudinal studies. CONCLUSIONS: Epigenetic
      intergenerational transmission, if at play in human populations, could have
      policy implications in terms of reducing the continuation of disadvantage across
      generations. Further research is needed to address this gap in the understanding
      of the perpetuation of compromised lives across generations.

PMID- 29473649
TI  - Detection of tilapia lake virus (TiLV) infection by PCR in farmed and wild Nile
      tilapia (Oreochromis niloticus) from Lake Victoria.
AB  - Tilapia lake virus disease (TiLVD) has emerged to be an important viral disease
      of farmed Nile tilapia (Oreochromis niloticus) having the potential to impede
      expansion of aquaculture production. There is a need for rapid diagnostic tools
      to identify infected fish to limit the spread in individual farms. We report the
      first detection of TiLV infection by PCR in farmed and wild Nile tilapia from
      Lake Victoria. There was no difference in prevalence between farmed and wild fish
      samples (p = .65), and of the 442 samples examined from 191 fish, 28 were
      positive for TiLV by PCR. In terms of tissue distribution, the head kidney
      (7.69%, N = 65) and spleen (10.99%, N = 191), samples had the highest prevalence
      (p < .0028) followed by heart samples (3.45%, N = 29). Conversely, the prevalence
      was low in the liver (0.71%, N = 140) and absent in brain samples (0.0%, N = 17),
      which have previously been shown to be target organs during acute infections.
      Phylogenetic analysis showed homology between our sequences and those from recent
      outbreaks in Israel and Thailand. Given that these findings were based on nucleic
      acid detection by PCR, future studies should seek to isolate the virus from fish
      in Lake Victoria and show its ability to cause disease and virulence in
      susceptible fish.

PMID- 29473650
TI  - Lipid catabolism in microalgae.
AB  - Lipid degradation processes are important in microalgae because survival and
      growth of microalgal cells under fluctuating environmental conditions require
      permanent remodeling or turnover of membrane lipids as well as rapid mobilization
      of storage lipids. Lipid catabolism comprises two major spatially and temporarily
      separated steps, namely lipolysis, which releases fatty acids and head groups and
      is catalyzed by lipases at membranes or lipid droplets, and degradation of fatty
      acids to acetyl-CoA, which occurs in peroxisomes through the beta-oxidation
      pathway in green microalgae, and can sometimes occur in mitochondria in some
      other algal species. Here we review the current knowledge on the enzymes and
      regulatory proteins involved in lipolysis and peroxisomal beta-oxidation and
      highlight gaps in our understanding of lipid degradation pathways in microalgae.
      Metabolic use of acetyl-CoA products via glyoxylate cycle and gluconeogenesis is
      also reviewed. We then present the implication of various cellular processes such
      as vesicle trafficking, cell cycle and autophagy on lipid turnover. Finally,
      physiological roles and the manipulation of lipid catabolism for biotechnological
      applications in microalgae are discussed.

PMID- 29473651
TI  - Phenolic root exudate and tissue compounds vary widely among temperate forest
      tree species and have contrasting effects on soil microbial respiration.
AB  - Root-soil interactions fundamentally affect the terrestrial carbon (C) cycle and
      thereby ecosystem feedbacks to climate change. This study addressed the question
      of whether the secondary metabolism of different temperate forest tree species
      can affect soil microbial respiration. We hypothesized that phenolics can both
      increase and decrease respiration depending on their function as food source,
      mobilizer of other soil resources, signaling compound, or toxin. We analyzed the
      phenolic compounds from root exudates and root tissue extracts of six tree
      species grown in a glasshouse using high-performance liquid chromatography. We
      then tested the effect of individual phenolic compounds, representing the major
      identified phenylpropanoid compound classes, on microbial respiration through a 5
      d soil incubation. Phenolic root profiles were highly species-specific. Of the
      eight classes identified, flavonoids were the most abundant, with flavanols being
      the predominating sub-class. Phenolic effects on microbial respiration ranged
      from a 26% decrease to a 46% increase, with reduced respiration occurring in the
      presence of compounds possessing a catechol ring. Tree species variation in root
      phenolic composition influences the magnitude and direction of root effects on
      microbial respiration. Our data support the hypothesis that functional group
      rather than biosynthetic class determines the root phenolic effect on soil C
      cycling.

PMID- 29473652
TI  - In Vitro Evaluation of ECG-Synchronized Pulsatile Flow Using the i-cor Diagonal
      Pump in Neonatal and Pediatric ECLS Systems.
AB  - The objective was to assess the i-cor electrocardiogram-synchronized diagonal
      pump in terms of hemodynamic energy properties for off-label use in neonatal and
      pediatric extracorporeal life support (ECLS) circuits. The neonatal circuit
      consisted of an i-cor pump and console, a Medos Hilite 800 LT oxygenator, an 8Fr
      arterial cannula, a 10Fr venous cannula, 91 cm of 0.6-cm ID arterial tubing, and
      91 cm of 0.6-cm ID venous tubing. The pediatric circuit was identical except it
      included a 12Fr arterial cannula, a 14Fr venous cannula, and a Medos Hilite 2400
      LT oxygenator. Neonatal trials were conducted at 36 degrees C with hematocrit 40%
      using varying flow rates (200-600 mL/min, 200 mL increments) and postarterial
      cannula pressures (40-100 mm Hg, 20 mm Hg increments) under nonpulsatile mode and
      pulsatile mode with various pulsatile amplitudes (1000-4000 rpm, 1000 rpm
      increments). Pediatric trials were conducted at different flow rates (800-1600
      mL/min, 400 mL/min increments). Mean pressure and energy equivalent pressure
      increased with increasing postarterial cannula pressure, flow rate, and pulsatile
      amplitude. Physiologic-like pulsatility was achieved between pulsatile amplitudes
      of 2000-3000 rpm. Pressure drops were greatest across the arterial cannula.
      Pulsatile flow generated significantly higher total hemodynamic energy (THE)
      levels than nonpulsatile flow. THE levels at postarterial cannula site increased
      with increasing postarterial cannula pressure, pulsatile amplitude, and flow
      rate. No surplus hemodynamic energy (SHE) was generated under nonpulsatile mode.
      Under pulsatile mode, preoxygenator SHE increased with increasing postarterial
      cannula pressure and pulsatile amplitude, but decreased with increasing flow
      rate. The i-cor system can provide nonpulsatile and pulsatile flow for neonatal
      and pediatric ECLS. Pulsatile amplitudes of 2000-3000 rpm are recommended for use
      in neonatal and pediatric patients.

PMID- 29473653
TI  - Manipulating parameters of reinforcement to reduce problem behavior without
      extinction.
AB  - Differential reinforcement of alternative behavior (DRA) most often includes
      extinction as a treatment component. However, extinction is not always feasible
      and it can be counter-therapeutic if implemented without optimal treatment
      integrity. Researchers have successfully implemented DRA without extinction by
      manipulating various parameters of reinforcement such that alternative behavior
      is favored. We extended previous research by assessing three participants'
      sensitivities to quality, magnitude, and immediacy using arbitrary responses and
      reinforcers that maintain problem behavior. The results were used to implement an
      intervention for problem behavior using DRA without extinction. Our findings
      indicate that arbitrary responses can be used to identify individual and relative
      sensitivity to parameters of reinforcement for reinforcers that maintain problem
      behavior. Treatment was effective for all participants when we manipulated
      parameters of reinforcement to which they were most sensitive, and, for two
      participants, the treatment was less effective when we manipulated parameters to
      which they were least sensitive.

PMID- 29473654
TI  - Using equivalence-based instruction to teach piano skills to college students.
AB  - The purpose of the current study was to evaluate the effects of equivalence-based
      instruction (EBI) on the emergence of basic music reading and piano playing
      skills. Six female college students learned to identify three musical chord
      notations given their respective dictated names. Participants also learned to
      play chords on the piano following the dictated name of the chord, and to play
      the chords to a song on a keyboard. Results are consistent with past research, in
      that stimuli became substitutable for each other and acquired a common behavioral
      function. Data suggest that EBI was an effective and efficient procedure to teach
      adults to read musical notation, as well as play chords and a song on a piano
      keyboard.

PMID- 29473655
TI  - Characterization of the genetic factors affecting quinolizidine alkaloid
      biosynthesis and its response to abiotic stress in narrow-leafed lupin (Lupinus
      angustifolius L.).
AB  - Quinolizidine alkaloids (QAs) are toxic secondary metabolites that complicate the
      end use of narrow-leafed lupin (NLL; Lupinus angustifolius L.) grain, as levels
      sometimes exceed the industry limit for its use as a food and feed source. The
      genotypic and environmental influences on QA production in NLL are poorly
      understood. Here, the expression of QA biosynthetic genes was analysed in
      vegetative and reproductive tissues of bitter (high QA) and sweet (low QA)
      accessions. It was demonstrated that sweet accessions are characterized by lower
      QA biosynthetic gene expression exclusively in leaf and stem tissues than bitter
      NLL, consistent with the hypothesis that QAs are predominantly produced in aerial
      tissues and transported to seeds, rather than synthesized within the seed itself.
      This analysis informed our identification of additional candidate genes involved
      in QA biosynthesis. Drought and temperature stress are two major abiotic stresses
      that often occur during NLL pod set. Hence, we assessed the effect of drought,
      increased temperature, and their combination, on QA production in three sweet NLL
      cultivars. A cultivar-specific response to drought and temperature in grain QA
      levels was observed, including the identification of a cultivar where alkaloid
      levels did not change with these stress treatments.

PMID- 29473656
TI  - alpha-synuclein (SNCA) but not dynamin 3 (DNM3) influences age at onset of
      leucine-rich repeat kinase 2 (LRRK2) Parkinson's disease in Spain.
AB  - OBJECTIVES: A recent study showed that Arab-Berbers GG homozygous at
      rs2421947(C/G) in the dynamin 3 gene (DNM3) had 12.5 years earlier age at onset
      of leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD)
      (L2PD). We explored whether this variant modulates the L2PD age at onset in
      Spain. METHODS: We genotyped rs2421947 in 329 participants (210 L2PD patients,
      119 L2PD nonmanifesting p.G2019S carriers), and marker rs356219 (A/G) in the
      alpha-synuclein gene (SNCA). RESULTS: By Kaplan Meier and Cox regression
      analyses, we did not find an association of the DNM3 polymorphism with L2PD age
      at onset. However, we found an association of the SNCA marker with up to an 11
      years difference in the L2PD median age at onset (58 years for GG carriers vs 69
      years for AA). CONCLUSION: Our results indicate that SNCA rs356219 but not
      dynamin 3 DNM3 rs2421947 modifies the penetrance of the mutation G2019S in the
      Spanish population by influencing the L2PD age at onset. These findings suggest
      that different genetic modifiers may influence the L2PD age at onset in different
      populations. (c) 2018 International Parkinson and Movement Disorder Society.

PMID- 29473657
TI  - Fermentable short chain carbohydrate (FODMAP) content of common plant-based foods
      and processed foods suitable for vegetarian- and vegan-based eating patterns.
AB  - BACKGROUND: The low FODMAP (fermentable, oligo-, di-, mono-saccharides and
      polyols) diet is an effective strategy to improve symptoms of irritable bowel
      syndrome. However, combining the low FODMAP diet with another dietary restriction
      such as vegetarianism/veganism is challenging. Greater knowledge about the FODMAP
      composition of plant-based foods and food processing practices common to
      vegetarian/vegan eating patterns would assist in the implementation of the diet
      in this patient population. The present study aimed to quantify the FODMAP
      content of plant-based foods common in vegetarian/vegan diets and to investigate
      whether food processing can impact FODMAP levels. METHODS: Total FODMAP content
      was quantified in 35 foods, including fructose-in-excess-of-glucose, lactose,
      sorbitol, mannitol, galacto-oligosaccharide and total fructan, using high
      performance-liquid-chromatography and enzymatic assays. The effects of cooking,
      sprouting, pickling, fermentation, activation and canning on FODMAP content were
      assessed. The Monash University criteria to classify foods as low FODMAP was
      used. RESULTS: Of the 35 foods, 20 were classified as low FODMAP, including
      canned coconut milk (0.24 g serve-1 ), dulse (0.02 serve-1 ), nutritional yeast
      (0.01 serve-1 ), soy cheese (0.03 serve-1 ), tempeh (0.26 serve-1 ), wheat gluten
      (0.13 serve-1 ) and wheat grass (0.05 serve-1 ). No FODMAPs were detected in agar
      agar, egg replacer, vegan egg yolk, kelp noodles and spirulina. Food processing
      techniques that produced the greatest reduction in FODMAP content included
      pickling and canning. CONCLUSIONS: The present study provides a greater FODMAP
      composition knowledge of plant-based foods that can now be applied to the
      dietetic management of vegetarians/vegans requiring a low FODMAP diet. Food
      processing lowered the FODMAP content of foods, thereby increasing options for
      patients following a low FODMAP diet.

PMID- 29473658
TI  - Gadolinium as a new emerging contaminant of aquatic environments.
AB  - Since the 1980s, gadolinium (Gd)-based contrast agents (GBCAs) have been
      routinely used in magnetic resonance imaging as stable chelates of the Gd3+ ion,
      without toxic effects. Generally, GBCAs are considered some of the safest
      contrast agents. However, it has been observed that they can accumulate in
      patient tissue, bone, and probably brain (causing nephrogenic systemic fibrosis
      in patients with kidney failure or insufficiency and disturbance of calcium
      homeostasis in the organism). The GBCAs are predominantly removed renally without
      metabolization. Subsequently, they do not undergo degradation processes in
      wastewater-treatment plants and are emitted into the aquatic ecosystem. Their
      occurrence was confirmed in surface waters (up to 1100 ng/L), sediments (up to
      90.5 MUg/g), and living organisms. Based on a literature review, there is a need
      to investigate the contamination of different ecosystems and to ascertain the
      environmental fate of Gd. Long-term ecotoxicological data, degradation,
      metabolism, bioaccumulation processes, and biochemical effects of the Gd
      complexes should be explored. These data can be used to assess detailed
      environmental risks because currently only hotspots with high levels of Gd can be
      marked as dangerous for aquatic environments according to environmental risk
      assessments. Environ Toxicol Chem 2018;37:1523-1534. (c) 2018 SETAC.

PMID- 29473659
TI  - A Water-Soluble, Two-Photon Probe for Imaging Endogenous Hypochlorous Acid in
      Live Tissue.
AB  - Detection of hypochlorous acid (HClO) in the living system may help to uncover
      its essential biological functions. However, current imaging agents suffer from
      poor water solubility that limit their live-tissue applications. Here, a water
      soluble probe (NNH) is devised through innovative hydrazone modification of 1,8
      naphthalimide at 3' position. NNH was successfully applied to tracking endogenous
      HClO in both cultured macrophages and a liver injury model in mice. NNH
      demonstrated remarkably increased water solubility and multiple desirable
      features including two-photon absorbance, anti-bleaching capability, rapid
      cellular uptake, and low cytotoxicity. NNH is the first hydrazone-based probe for
      real-time imaging of HClO in live tissue.

PMID- 29473660
TI  - Direct and indirect pathways for choosing objects and actions.
AB  - A prominent target of the basal ganglia is the superior colliculus (SC) which
      controls gaze orientation (saccadic eye movement in primates) to an important
      object. This 'object choice' is crucial for choosing an action on the object. SC
      is innervated by the substantia nigra pars reticulata (SNr) which is controlled
      mainly by the caudate nucleus (CD). This CD-SNr-SC circuit is sensitive to the
      values of individual objects and facilitates saccades to good objects. The object
      values are processed differently in two parallel circuits: flexibly by the
      caudate head (CDh) and stably by the caudate tail (CDt). To choose good objects,
      we need to reject bad objects. In fact, these contrasting functions are
      accomplished by the circuit originating from CDt: The direct pathway focuses on
      good objects and facilitates saccades to them; the indirect pathway focuses on
      bad objects and suppresses saccades to them. Inactivation of CDt deteriorated the
      object choice, because saccades to bad objects were no longer suppressed. This
      suggests that the indirect pathway is important for object choice. However, the
      direct and indirect pathways for 'object choice', which aim at the same action
      (i.e., saccade), may not work for 'action choice'. One possibility is that
      circuits controlling different actions are connected through the indirect
      pathway. Additional connections of the indirect pathway with brain areas outside
      the basal ganglia may also provide a wider range of behavioral choice. In
      conclusion, basal ganglia circuits are composed of the basic direct/indirect
      pathways and additional connections and thus have acquired multiple functions.

PMID- 29473662
TI  - MRI supervised and unsupervised classification of Parkinson's disease and
      multiple system atrophy.
AB  - BACKGROUND: Multimodal MRI approach is based on a combination of MRI parameters
      sensitive to different tissue characteristics (eg, volume atrophy, iron
      deposition, and microstructural damage). The main objective of the present study
      was to use a multimodal MRI approach to identify brain differences that could
      discriminate between matched groups of patients with multiple system atrophy,
      Parkinson's disease, and healthy controls. We assessed the 2 different MSA
      variants, namely, MSA-P, with predominant parkinsonism, and MSA-C, with more
      prominent cerebellar symptoms. METHODS: Twenty-six PD patients, 29 MSA patients
      (16 MSA-P, 13 MSA-C), and 26 controls underwent 3-T MRI comprising T2*-weighted,
      T1-weighted, and diffusion tensor imaging scans. Using whole-brain voxel-based
      MRI, we combined gray-matter density, T2* relaxation rates, and diffusion tensor
      imaging scalars to compare and discriminate PD, MSA-P, MSA-C, and healthy
      controls. RESULTS: Our main results showed that this approach reveals
      multiparametric modifications within the cerebellum and putamen in both MSA-C and
      MSA-P patients, compared with PD patients. Furthermore, our findings revealed
      that specific single multimodal MRI markers were sufficient to discriminate MSA-P
      and MSA-C patients from PD patients. Moreover, the unsupervised analysis based on
      multimodal MRI data could regroup individuals according to their clinical
      diagnosis, in most cases. CONCLUSIONS: This study demonstrates that multimodal
      MRI is able to discriminate patients with PD from those with MSA with high
      accuracy. The combination of different MR biomarkers could be a great tool in
      early stage of disease to help diagnosis. (c) 2018 International Parkinson and
      Movement Disorder Society.

PMID- 29473663
TI  - Long-term clinicopathologic observation in a case of steroid-resistant nephrotic
      syndrome caused by a novel Crumbs homolog 2 mutation.
AB  - Recent advances in high-throughput sequencing for clinical genetic testing have
      revealed novel disease-causing genes, such as Crumbs homolog 2 (CRB2) for early
      onset steroid-resistant nephrotic syndrome (SRNS). We report the long-term
      clinicopathologic observation of a Japanese female patient with SRNS caused by a
      newly identified compound heterozygous mutation of CRB2 (p.Arg628Cys and
      p.Gly839Trp located in the 10th and 11th epidermal growth factor-like domains,
      respectively). She was initially examined during a mass urinary screening for 3.5
      year-old children in Japan. Although she developed long-standing SRNS without any
      extrarenal clinical signs thereafter, her renal function was well-preserved over
      the next 17 years. In total, six sequential renal biopsy specimens revealed
      histologic alterations ranging from minor glomerular abnormalities to advanced
      focal segmental glomerulosclerosis (FSGS). A genetic analysis for SRNS performed
      at 19 years of age revealed a newly identified compound heterozygous mutation in
      CRB2. Glomerular CRB2 immunoreactivity in biopsy specimens from the patient was
      scanty, whereas intense expression was observed in those from patients with
      idiopathic FSGS or in controls. To our knowledge, this is the first report
      regarding a long-term outcome in a case of SRNS due to an identified CRB2
      mutation. Although the phenotype of CRB2 mutation-related syndrome is now
      expanding, we believe that this case might provide a novel clinicopathologic
      aspect of this syndrome.

PMID- 29473661
TI  - Facial emotion recognition in Parkinson's disease: A review and new hypotheses.
AB  - Parkinson's disease is a neurodegenerative disorder classically characterized by
      motor symptoms. Among them, hypomimia affects facial expressiveness and social
      communication and has a highly negative impact on patients' and relatives'
      quality of life. Patients also frequently experience nonmotor symptoms, including
      emotional-processing impairments, leading to difficulty in recognizing emotions
      from faces. Aside from its theoretical importance, understanding the disruption
      of facial emotion recognition in PD is crucial for improving quality of life for
      both patients and caregivers, as this impairment is associated with heightened
      interpersonal difficulties. However, studies assessing abilities in recognizing
      facial emotions in PD still report contradictory outcomes. The origins of this
      inconsistency are unclear, and several questions (regarding the role of dopamine
      replacement therapy or the possible consequences of hypomimia) remain unanswered.
      We therefore undertook a fresh review of relevant articles focusing on facial
      emotion recognition in PD to deepen current understanding of this nonmotor
      feature, exploring multiple significant potential confounding factors, both
      clinical and methodological, and discussing probable pathophysiological
      mechanisms. This led us to examine recent proposals about the role of basal
      ganglia-based circuits in emotion and to consider the involvement of facial
      mimicry in this deficit from the perspective of embodied simulation theory. We
      believe our findings will inform clinical practice and increase fundamental
      knowledge, particularly in relation to potential embodied emotion impairment in
      PD. (c) 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc.
      on behalf of International Parkinson and Movement Disorder Society.

PMID- 29473664
TI  - A General Approach to Access Morphologies of Polyoxometalates in Solution by
      Using SAXS: An Ab Initio Modeling Protocol.
AB  - Herein, we reported a general protocol for an ab initio modeling approach to
      deduce structure information of polyoxometalates (POMs) in solutions from
      scattering data collected by the small-angle X-ray scattering (SAXS) technique.
      To validate the protocol, the morphologies of a serious of known POMs in either
      aqueous or organic solvents were analyzed. The obtained particle morphologies
      were compared and confirmed with previous reported crystal structures. To extend
      the feasibility of the protocol to an unknown system of aqueous solutions of Na2
      MoO4 with the pH ranging from -1 to 8.35, the formation of {Mo36 } clusters was
      probed, identified, and confirmed by SAXS. The approach was further optimized
      with a multi-processing capability to achieve fast analysis of experimental data,
      thereby, facilitating in situ studies of formations of POMs in solutions. The
      advantage of this approach is to generate intuitive 3D models of POMs in
      solutions without confining information such as symmetries and possible sizes.

PMID- 29473665
TI  - Lower-limb muscle function during gait in varus mal-aligned osteoarthritis
      patients.
AB  - This study quantified the contributions by muscular, gravitational and inertial
      forces to the ground reaction force (GRF) and external knee adduction moment
      (EKAM) for knee osteoarthritis (OA) patients and controls walking at similar
      speeds. Gait data for 39 varus mal-aligned medial knee OA patients and 15
      controls were input into musculoskeletal models to calculate the contributions of
      individual muscles and gravity to the fore-aft (progression), vertical (support),
      and mediolateral (balance) GRF, and the EKAM. The temporal patterns of
      contributions to GRF and EKAM were similar between the groups. Magnitude
      differences in GRF contributions were small but some reached significance. Peak
      GRF contributions were lower in patients except hamstrings in early-stance
      progression (p < 0.001) and gastrocnemius in late-stance progression (p < 0.001).
      Both EKAM peaks were higher in patients, due mainly to greater adduction
      contribution from gravity (p < 0.001) at the first peak, and lower abduction
      contributions from soleus (p < 0.001) and gastrocnemius (p < 0.001) at the second
      peak. Gluteus medius contributed most to EKAM in both groups, but was higher in
      patients during mid-stance only (p < 0.001). Differences in GRF contributions
      were attributed to altered quadriceps-hamstrings action as well as compensatory
      adaptation of the ankle plantarflexors to reduced gluteus medius action. The
      large effect of varus mal-alignment on the frontal-plane moment arms of the
      gravity, soleus, and gastrocnemius GRF contributions about the knee explained
      greater patient EKAM. Our results shed further light on how the EKAM contributes
      to altered knee-joint loads in OA and why some interventions may affect different
      portions of the EKAM waveform. (c) 2018 Orthopaedic Research Society. Published
      by Wiley Periodicals, Inc. J Orthop Res.

PMID- 29473666
TI  - Validation of a dynamic joint contracture measuring device in a live rabbit model
      of arthrofibrosis.
AB  - The current method of measuring arthrofibrosis in live rabbits is critically
      limited. Specifically, this method involves radioactive fluoroscopy, error-prone
      goniometric measurements, and static joint angle outcomes that fail to
      approximate the compliance of tissues surrounding the joint. This study aims to
      validate a novel method of capturing the compliance of contracted tissues
      surrounding the joint without the use of fluoroscopy or animal sacrifice.
      Surgically induced contractures of one-hundred and eight rabbits were measured
      using the current standard of contracture measurement (a pulley system) as well
      as a newly designed dynamic load cell (DLC) device. The DLC device was highly
      reliable when compared to the pulley system (r = 0.907, p < 0.001). Finally, the
      DLC device produced joint stiffness hysteresis curves capable of approximating
      the compliance of stiff joint tissues, ultimately calculating a mean joint
      stiffness of 1.57 +/- 1.31 N . m . rad-1 (range, 0.33-6.37 N . m . rad-1 ). In
      conclusion, the DLC device represents a valid method for measuring joint
      contractures. Further, the DLC device notably improves current techniques by
      introducing the capacity to approximate the compliance of contracted tissues in
      living rabbits. (c) 2018 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res.

PMID- 29473667
TI  - Open Chain Polyarsenides of the Lanthanides.
AB  - The reaction of [(Cp'''Co)2 (MU,eta2:2 -As2 )2 ] with the decamethylsamarocenes
      [Cp*2 Sm(THF)2 ] or [Cp*2 Sm], or the bis(tetramethyl-n-propyl)samarocene [(C5
      Me4 (n-propyl))2 Sm] resulted in the mixed d/f polyarsenides [(Cp'''Co)2 As4
      Sm(eta5 -C5 Me4 R)2 ] (R=Me, n-propyl). They are the first structural
      representatives of open chain-like polyarsenides as ligands in the coordination
      sphere of lanthanides. Their formation can be explained by an intramolecular As
      As coupling within the cobalt polyarsenide complex after reduction by the
      divalent samarium complex. Density functional theory calculations give insight
      into the structural change of the (As2 )2 unit in [{Cp'''Co(MU,eta2:2 -As2 )}2 ]
      upon reduction.

PMID- 29473668
TI  - ACS National Awards 2018.

PMID- 29473669
TI  - Effects of soot by-product from the synthesis of engineered metallofullerene
      nanomaterials on terrestrial invertebrates.
AB  - The synthesis of carbon-based nanomaterials is often inefficient, generating
      large amounts of soot with metals as waste by-product. Currently, there are no
      specific regulations for disposal of engineered nanomaterials or the waste by
      products resulting from their synthesis, so it is presumed that by-products are
      disposed of in the same way as the parent (bulk) materials. We studied the
      terrestrial toxicity of soot from gadolinium metallofullerene nanomanufacturing
      on earthworms (Eisenia fetida) and isopods (Porcellio scaber). The
      metallofullerene soot consisted of carbon particle agglomerates in the nanometer
      and submicrometer ranges (1-100 and 101-999 nm, respectively), with metals used
      during nanomanufacturing detectable on the particles. Despite high metal
      concentrations (>100 000 mg/kg) in the soot, only a relatively small amount of
      metals leached out of a spiked field soil, suggesting only moderate mobility.
      Seven- and 14-d exposures in field soil demonstrated that the soot was only toxic
      to earthworms at high concentrations (>10 000 mg/kg); however, earthworms avoided
      spiked soils at lower concentrations (as low as 500 mg/kg) and at lower soil pH.
      The presence of soot in food and soil did not cause isopod avoidance. These data
      demonstrate that metallofullerene soot from nanomanufacturing may only be toxic
      to earthworms at high concentrations representative of improper disposal or
      accidental spills. However, our results indicate that terrestrial invertebrates
      may avoid soils contaminated with soot at sublethal concentrations. Environ
      Toxicol Chem 2018;9999:1-12. Published 2018 Wiley Periodicals, Inc. on behalf of
      SETAC. This article is a US government work, and as such, is in the public domain
      in the United States of America.

PMID- 29473670
TI  - Some assembly required: Contributions of Tom Stevens' lab to the V-ATPase field.
AB  - Tom Stevens' lab has explored the subunit composition and assembly of the yeast V
      ATPase for more than 30 years. Early studies helped establish yeast as the
      predominant model system for study of V-ATPase proton pumps and led to the
      discovery of protein splicing of the V-ATPase catalytic subunit. The Vma-
      phenotype, characteristic of loss-of-V-ATPase activity in yeast was key in
      determining the enzyme's subunit composition via yeast genetics. V-ATPase subunit
      composition proved to be highly conserved among eukaryotes. Genetic screens for
      new vma mutants led to identification of a set of dedicated V-ATPase assembly
      factors and helped unravel the complex pathways for V-ATPase assembly. In later
      years, exploration of the evolutionary history of several V-ATPase subunits
      provided new information about the enzyme's structure and function. This review
      highlights V-ATPase work in the Stevens' lab between 1987 and 2017.

PMID- 29473672
TI  - Fertility treatment: Getting stressed about stress.

PMID- 29473673
TI  - Mississippian subadults from the Middle Cumberland and Eastern regions of
      Tennessee: Biological indicators of population interaction.
AB  - OBJECTIVES: Human subadult skeletal remains can provide a unique perspective into
      biosocial aspects of Mississippian period population interactions within and
      between the Middle Cumberland (MCR) and Eastern Tennessee Regions (ETR). The
      majority of previous studies have concentrated on adult skeletal remains, leaving
      out a large and extremely important population segment. METHODS: Skeletal
      indicators of disease, growth, body proportions, and metabolic stress were
      collected from subadult remains from five archaeological sites over several
      temporal periods. Crucial to overcoming limitations associated with the
      osteological paradox, the biological results were placed into an archaeological
      context based on prior studies as well as paleoclimatological data. RESULTS:
      Results reveal homogeneity both within and between regions for most skeletal
      indicators. However, MCR individuals exhibit a higher frequency of pathology than
      those from ETC, while stature is significantly lower in younger subadults from
      the MCR. Within the ETR, there is no evidence for biological differences between
      Early Dallas and subsequent Late Dallas and Mouse Creek cultural phases. Despite
      presumed signs of increased conflict at the Dallas site, frequencies and types of
      skeletal pathology and growth disruptions are comparable to other regional sites.
      CONCLUSIONS: These findings suggest that despite cultural differences between the
      ETR and MCR, there was no large-scale intrusion from an outside population into
      the ETR during the Late Mississippian Period, or if one occurred, it is
      biologically invisible. Combined with climatic and archaeobotanical data, results
      suggest the MCR subadults were under increased stress in their earlier years.
      This may have been associated with increased interpersonal violence and
      dependence on few food sources occurring with greater scarcity.

PMID- 29473674
TI  - Occurrence of two novel viral pathogens (CEV and CyHV-2) affecting Serbian
      cyprinid aquaculture and ichthyofauna.

PMID- 29473675
TI  - Contemporary Oxygenator Design: Shear Stress-Related Oxygen and Carbon Dioxide
      Transfer.
AB  - Design of contemporary oxygenators requires better understanding of the influence
      of hydrodynamic patterns on gas exchange. A decrease in blood path width or an
      increase in intraoxygenator turbulence for instance, might increase gas transfer
      efficiency but it will increase shear stress as well. The aim of this clinical
      study was to examine the association between shear stress and oxygen and carbon
      dioxide transfer in different contemporary oxygenators during cardiopulmonary
      bypass (CPB). The effect of additional parameters related to gas transfer
      efficiency, that is, blood flow, gas flow, sweep gas oxygen fraction (FiO2 ),
      hemoglobin concentration, the amount of hemoglobin pumped through the oxygenator
      per minute-Qhb, and shunt fraction were contemplated as well. Data from 50 adult
      patients who underwent elective CPB for coronary artery bypass grafting or aortic
      valve replacement were retrospectively analyzed. Data included five different
      oxygenator types with an integrated arterial filter. Relationships were
      determined using Pearson bivariate correlation analysis and scatterplots with
      LOESS curves. In the Capiox FX25, Fusion, Inspire 8F, Paragon, and Quadrox-i
      groups, mean blood flows were 4.8 +/- 0.9, 5.3 +/- 0.7, 4.9 +/- 0.7, 5.0 +/- 0.6,
      and 5.7 +/- 0.6 L/min, respectively. The mean O2 transfer/m2 membrane surface
      area was 44 +/- 14, 51 +/- 9, 60 +/- 10, 63 +/- 14, and 77 +/- 18, respectively,
      whereas the mean CO2 transfer/m2 was 26 +/- 14, 60 +/- 22, 73 +/- 29, 74 +/- 19,
      and 96 +/- 20, respectively. Associations between oxygen transfer/m2 and shear
      stress differed per oxygenator, depending on oxygenator design and the level of
      shear stress (r = 0.249, r = 0.562, r = 0.402, r = 0.465, and r = 0.275 for
      Capiox FX25, Fusion, Inspire 8F, Paragon, and Quadrox-i, respectively, P < 0.001
      for all). Similar associations were noted between CO2 transfer/m2 and shear
      stress (r = 0.303, r = 0.439, r = 0.540, r = 0.392, and r = 0.538 for Capiox
      FX25, Fusion, Inspire 8F, Paragon, and Quadrox-i, respectively, P < 0.001 for
      all). In addition, O2 transfer/m2 was strongly correlated with FiO2 (r = 0.633, P
      < 0.001), blood flow (r = 0.529, P < 0.001), and Qhb (r = 0.589, P < 0.001). CO2
      transfer/m2 in contrast was predominately correlated to sweep gas flow (r =
      0.567, P < 0.001). The design-dependent relationship between shear stress and gas
      transfer revealed that every oxygenator has an optimal range of blood flow and
      thus shear stress at which gas transfer is most efficient. Gas transfer is
      further affected by factors influencing the O2 or CO2 concentration gradient
      between the blood and the gas compartment.

PMID- 29473677
TI  - Wanted dead or alive: Polydora websteri recruit to both live oysters and empty
      shells of the eastern oyster, Crassostrea virginica.

PMID- 29473678
TI  - The Hattie Hemschemeyer Award 2016: Holly Powell Kennedy, CNM, PhD, FACNM, FAAN.

PMID- 29473681
TI  - National Partnership for Maternal Safety: Consensus Bundle on Venous
      Thromboembolism.
AB  - Obstetric venous thromboembolism is a leading cause of severe maternal morbidity
      and mortality. Maternal death from thromboembolism is amenable to prevention, and
      thromboprophylaxis is the most readily implementable means of systematically
      reducing the maternal death rate. Observational data support the benefit of risk
      factor-based prophylaxis in reducing obstetric thromboembolism. This bundle,
      developed by a multidisciplinary working group and published by the National
      Partnership for Maternal Safety under the guidance of the Council on Patient
      Safety in Women's Health Care, supports routine thromboembolism risk assessment
      for obstetric patients, with appropriate use of pharmacologic and mechanical
      thromboprophylaxis. Safety bundles outline critical clinical practices that
      should be implemented in every maternity unit. The safety bundle is organized
      into 4 domains: Readiness, Recognition, Response, and Reporting and Systems
      Learning. Although the bundle components may be adapted to meet the resources
      available in individual facilities, standardization within an institution is
      strongly encouraged.

PMID- 29473682
TI  - Associations of postoperative mortality with the time of day, week and year.
AB  - Studies that have investigated circadian, weekday and seasonal variation in
      postoperative mortality have been relatively small or have been for scheduled
      surgery. We retrospectively tested a large mixed surgical cohort from a German
      tertiary care university hospital for the presence of cyclical variation in all
      cause in-hospital mortality after operations performed between 2006 and 2013. We
      analysed mortality rates after 247,475 operations, adjusted for age, sex,
      comorbidities, location, urgency and duration of the surgery, and intra-operative
      blood transfusions. The mortality odds ratio (95%CI) after operations started in
      the morning (08:00-11:00) were lowest, 0.73 (0.66-0.80), p < 0.001 and highest
      for operations started in the afternoon (13:00-17:00), 1.29 (1.18-1.40), p <
      0.001. Mortality at the weekend was the same as during the week. There was no
      seasonal variation in mortality, p = 0.12. However, the interference of four
      yearly and ten-monthly cycle amplitudes resulted in higher mortality odds ratio
      (95%CI) in winter 2008-2009, 1.41 (1.18-1.69), p < 0.001, and lower mortality in
      spring 2011 and 2012, 0.70 (0.56-0.85) and 0.67 (0.53-0.85), p < 0.001 and p =
      0.001, respectively. The ability to predict cyclical phenomena would facilitate
      the design of interventional studies, aimed at reducing mortality following
      surgery in the afternoon and when cycles interfere constructively.

PMID- 29473684
TI  - CKAP2L mutation confirms the diagnosis of Filippi syndrome.

PMID- 29473686
TI  - Alternative Th17 and CD4+ CD25+ FoxP3+ cell frequencies increase and correlate
      with worse cardiac function in Chagas cardiomyopathy.
AB  - Immune homeostasis has been suggested to play an important role in the clinical
      evolution of chronic Chagas disease; however, the immunopathologic factors
      involved have not been fully elucidated. Therefore, our study aimed to analyse
      the frequency of CD4+ CD25+ FoxP3+ cells, classic Th17 cells, alternative Th17
      cells and IL-17+ B cells from peripheral blood of chronic cardiac patients after
      in vitro stimulation with Trypanosoma cruzi soluble EPI antigen. Patients were
      selected and classified according to clinical evaluation of cardiac involvement:
      mild, B1 (CARD1) (n = 20) and severe, C (CARD2) (n = 11). Patients with the
      indeterminate form of CD were included as the control group A (IND) (n = 17).
      Blood samples were collected and cultured in the presence of EPI antigen. Cells
      frequency and median fluorescence intensity (MFI) were obtained by flow
      cytometry. Our results showed that only CD4+ CD25+ FoxP3+ , CD4+ CD25high FoxP3+
      , CD4+ IL-17+ IFN-gamma- and CD4+ IL-17+ IFN-gamma+ cells are more frequent in
      patients with severe cardiac disease and correlate with worse global cardiac
      function. However, while indeterminate patients demonstrated a positive
      correlation between CD4+ CD25+ FoxP3+ and CD4+ IL-17+ IFN-gamma- Th17 cells, this
      relationship was not observed in cardiac patients. IL-17 expression by Th17 cells
      and B cells correlated with disease progression. Altogether our results suggest
      that the clinical progression of Chagas cardiomyopathy involves worsening of
      inflammation and impairment of immunoregulatory mechanisms.

PMID- 29473687
TI  - Effectiveness of oral chlorhexidine for the prevention of nosocomial pneumonia
      and ventilator-associated pneumonia in intensive care units: Overview of
      systematic reviews.
AB  - OBJECTIVE: To summarize evidence regarding the effectiveness of using
      chlorhexidine for oral healthcare on patients in the intensive care unit for the
      prevention of nosocomial pneumonia and ventilator-associated pneumonia. METHODS:
      This overview of systematic reviews was developed using articles found in PUBMED,
      Cochrane Library, LILACS, CRD, CINHAL, manual search and grey literature.
      RESULTS: Of the total 16 systematic reviews, 14 included meta-analysis. Most of
      them were classified with high methodological quality. In seven systematic
      reviews, chlorhexidine was effective for prevention of nosocomial pneumonia and
      ventilator-associated pneumonia in adult population in cardiothoracic intensive
      care unit. The effectiveness was contradictory with other population patients in
      intensive care units. CONCLUSION: Chlorhexidine has proven to be effective for
      the prevention of NP among adult populations in cardiothoracic ICU. In ICUs with
      patients who have varied clinical-surgical conditions, the effectiveness of
      chlorhexidine for the prevention of PN and VAP was inconclusive.

PMID- 29473690
TI  - ACNM Fellows Inducted in 2016.

PMID- 29473692
TI  - 1,8-Diphenyl-9,10-Bis(arylethynyl)phenanthrenes: Synthesis, Distorted Structure,
      and Optical Properties.
AB  - The synthesis and optical properties of 1,8-diphenyl-9,10
      bis(arylethynyl)phenanthrenes, which are distorted phenanthrenes, are reported.
      The presence of the two phenyl groups at the 1,8-positions of phenanthrene
      significantly distorts the molecular geometries, as was evidenced by X-ray
      crystallography. The congested substitution pattern in the K region results in a
      distorted aromatic framework, which leads to a redshift in the emission spectrum.
      These observations are in stark contrast to 9,10-bis(phenylethynyl)phenanthrene
      with no phenyl groups at the 1,8-positions. A large Stokes shift suggested
      extensive structural relaxation between the phenyl and arylethynyl units in the
      excited state, which was supported by theoretical calculations.

PMID- 29473691
TI  - Assessing cognitive dysfunction in Parkinson's disease: An online tool to detect
      visuo-perceptual deficits.
AB  - BACKGROUND: People with Parkinson's disease (PD) who develop visuo-perceptual
      deficits are at higher risk of dementia, but we lack tests that detect subtle
      visuo-perceptual deficits and can be performed by untrained personnel.
      Hallucinations are associated with cognitive impairment and typically involve
      perception of complex objects. Changes in object perception may therefore be a
      sensitive marker of visuo-perceptual deficits in PD. OBJECTIVE: We developed an
      online platform to test visuo-perceptual function. We hypothesised that (1) visuo
      perceptual deficits in PD could be detected using online tests, (2) object
      perception would be preferentially affected, and (3) these deficits would be
      caused by changes in perception rather than response bias. METHODS: We assessed
      91 people with PD and 275 controls. Performance was compared using classical
      frequentist statistics. We then fitted a hierarchical Bayesian signal detection
      theory model to a subset of tasks. RESULTS: People with PD were worse than
      controls at object recognition, showing no deficits in other visuo-perceptual
      tests. Specifically, they were worse at identifying skewed images (P < .0001); at
      detecting hidden objects (P = .0039); at identifying objects in peripheral vision
      (P < .0001); and at detecting biological motion (P = .0065). In contrast, people
      with PD were not worse at mental rotation or subjective size perception. Using
      signal detection modelling, we found this effect was driven by change in
      perceptual sensitivity rather than response bias. CONCLUSIONS: Online tests can
      detect visuo-perceptual deficits in people with PD, with object recognition
      particularly affected. Ultimately, visuo-perceptual tests may be developed to
      identify at-risk patients for clinical trials to slow PD dementia. (c) 2018 The
      Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of
      International Parkinson and Movement Disorder Society.

PMID- 29473693
TI  - Prediction of memory formation based on absolute electroencephalographic phases
      in rhinal cortex and hippocampus outperforms prediction based on stimulus-related
      phase shifts.
AB  - Absolute (i.e. measured) rhinal and hippocampal phase values are predictive for
      memory formation. It has been an open question, whether the capability of
      mediotemporal structures to react to stimulus presentation with phase shifts may
      be similarly indicative of successful memory formation. We analysed data from 27
      epilepsy patients implanted with depth electrodes in the hippocampus and
      entorhinal cortex, who performed a continuous word recognition task.
      Electroencephalographic phase information related to the first presentation of
      repeatedly presented words was used for prediction of subsequent remembering vs.
      forgetting applying a support vector machine. The capability to predict
      successful memory formation based on stimulus-related phase shifts was compared
      to that based on absolute phase values. Average hippocampal phase shifts were
      larger and rhinal phase shifts were more accumulated for later remembered
      compared to forgotten trials. Nevertheless, prediction based on absolute phase
      values clearly outperformed phase shifts and there was no significant increase in
      prediction accuracies when combining both measures. Our findings indicate that
      absolute rhinal and hippocampal phases and not stimulus-related phase shifts are
      most relevant for successful memory formation. Absolute phases possibly affect
      memory formation via influencing neural membrane potentials and thereby
      controlling the timing of neural firing.

PMID- 29473694
TI  - Comparing apples and oranges and pears and kumquats: The misuse of index systems
      for processing histopathology data in fish toxicological bioassays.
AB  - Histopathology index systems involve the application of weighted scores to
      various diagnostic findings for the purpose of calculating overall organ and/or
      whole-animal health measurements. Such systems were originally developed as tools
      for monitoring the general health of fish populations. More recently, index
      systems have been applied to hypothesis-based toxicological studies, the goal of
      which is to investigate whether a cause-and-effect relationship exists between
      exposure to a particular test substance or environmental contaminant and
      morphologic effects in fish tissues. However, the application of index systems in
      that context is problematic for various reasons: a dependency on untested
      assumptions of toxicological importance for different types of histopathologic
      findings; organ scores that combine mechanistically unrelated and potentially
      contradictory diagnoses; calculations that include excessive numbers of findings,
      some of which may be incidental to the study outcome; failure to incorporate
      additional relevant results into the data interpretation, such as clinical
      observations, macroscopic findings, organ/body weights, clinical pathology data,
      and the results of hormonal or other biochemical assays; the inappropriate
      mathematical manipulation of ordinal categorical data (e.g., severity scores and
      "importance factors"); and a tendency of these systems to amplify, mask, and
      divert attention from methodological weaknesses and inaccurate diagnoses. The
      purpose of the present article is to demonstrate why the use of index systems is
      a misguided approach for handling histopathology data in studies of potential
      fish toxicants. Environ Toxicol Chem 2018;37:1688-1695. (c) 2018 SETAC.

PMID- 29473695
TI  - Nanomaterial exposure, toxicity, and impact on human health.
AB  - The use of engineered nanomaterials (ENM) has grown after the turn of the 21st
      century. Also, the production of ENM has globally grown, and exposure of workers
      especially via the lungs to ENM has increased. This review tackles with effects
      of ENM on workers' health because occupational environment is the main source of
      exposure to ENM. Assessment of exposure to ENM is demanding, and today there are
      no occupational exposure level (OEL) for ENM. This is partly due to challenges of
      such measurements, and in part to the unknown causality between ENM metrics and
      effects. There are also marked gaps in systematic knowledge on ENM hazards. Human
      health surveys of exposed workers, or human field studies have not identified
      specific effects of ENM linking them with a specific exposure. There is, however,
      a consensus that material characteristics such as size, and chemistry influence
      effects of ENM. Available data suggest that multiwalled carbon nanotubes (MWCNT)
      affect the immunological system and cause inflammation of the lungs, or signs of
      asthma whereas carbon nanofibers (CNF) may cause interstitial fibrosis. Metallic
      and metal oxide nanoparticles together with MWCNT induce genotoxicity, and a
      given type of MWCNT has been identified as a possible human carcinogen.
      Currently, lack of understanding of mechanisms of effects of ENM renders
      assessment of hazards and risks of ENM material-by-material a necessity. The so
      called "omics" approaches utilizing ENM-induced alterations in gene and protein
      expression may be useful in the development of a new paradigm for ENM hazard and
      risk assessment. This article is categorized under: Toxicology and Regulatory
      Issues in Nanomedicine > Toxicology of Nanomaterials.

PMID- 29473696
TI  - Developing and testing a brief clinic-based lung cancer screening decision aid
      for primary care settings.
AB  - BACKGROUND: Cancer screening-related decisions require patients to evaluate
      complex medical information in short time frames, often with primary care
      providers (PCPs) they do not know. PCPs play an essential role in facilitating
      comprehensive shared decision making (SDM). OBJECTIVE: To develop and test a
      decision aid (DA) and SDM strategy for PCPs and high-risk patients. DESIGN: The
      DA was tested with 20 dyads. Each dyad consisted of one PCP and one patient
      eligible for screening. A prospective, one-group, mixed-method study design
      measured fidelity, patient values, screening intention, acceptability and
      satisfaction. RESULTS: Four PCPs and 20 patients were recruited from an urban
      academic medical centre. Most patients were female (n = 14, 70%), most had
      completed high school (n = 15, 75%), and their average age was 65 years old. Half
      were African American. Patients and PCPs rated the DA as helpful, easy to read
      and use and acceptable in terms of time frame (observed t = 11.6 minutes, SD
      2.7). Most patients (n = 16, 80%) indicated their intent to be screened. PCPs
      recommended screening for most patients (n = 17, 85%). CONCLUSIONS: Evidence
      supports the value of lung cancer screening with LDCT for select high-risk
      patients. Guidelines endorse engaging patients and their PCPs in SDM discussions.
      Our findings suggest that using a brief, interactive, plain-language, culturally
      sensitive, theory-based DA and SDM strategy is feasible, acceptable and may be
      essential to effectively translate and sustain the adoption of LDCT screening
      recommendations into the clinic setting.

PMID- 29473697
TI  - Distinct clusters of stunted children in India: An observational study.
AB  - Childhood stunting is often conceptualised as a singular concept (i.e., stunted
      or not), and such an approach implies similarity in the experiences of children
      who are stunted. Furthermore, risk factors for stunting are often treated in
      isolation, and limited research has examined how multiple risk factors interact
      together. Our aim was to examine whether there are subgroups among stunted
      children, and if parental characteristics influence the likelihood of these
      subgroups among children. Children who were stunted were identified from the 2005
      2006 Indian National Family Health Survey (n = 12,417). Latent class analysis was
      used to explore the existence of subgroups among stunted children by their
      social, demographic, and health characteristics. We examined whether parental
      characteristics predicted the likelihood of a child belonging to each latent
      class using a multinomial logit regression model. We found there to be 5 distinct
      groups of stunted children; "poor, older, and poor health-related outcomes,"
      "poor, young, and poorest health-related outcomes," "poor with mixed health
      related outcomes," "wealthy and good health-related outcomes," and "typical
      traits." Both mother and father's educational attainment, body mass index, and
      height were important predictors of class membership. Our findings demonstrate
      evidence that there is heterogeneity of the risk factors and behaviours among
      children who are stunted. It suggests that stunting is not a singular concept;
      rather, there are multiple experiences represented by our "types" of stunting.
      Adopting a multidimensional approach to conceptualising stunting may be important
      for improving the design and targeting of interventions for managing stunting.

PMID- 29473698
TI  - A proof-of-concept pilot randomized comparative trial of brief Internet-based
      compassionate mind training and cognitive-behavioral therapy for perinatal and
      intending to become pregnant women.
AB  - OBJECTIVE: Depression is a prevalent and costly mental health problem that
      affects women as well as their larger communities, with substantial impacts on
      mother and infant during childbearing years. Face-to-face care has not adequately
      addressed this global concern due to difficulties in scaling these resources.
      Internet interventions, which can provide psychological tools to those lacking
      adequate access, show promise in filling this void. METHOD: We conducted a 2
      condition proof-of-concept pilot randomized trial comparing brief Internet-based
      cognitive behavioural therapy (CBT) and brief Internet-based compassionate mind
      training (CMT) for women who are currently pregnant, became pregnant within the
      last year, and intend to become pregnant in the future. RESULTS: We found that,
      although CMT and CBT demonstrated near equivalence in improving affect, self
      reassurance, self-criticism, and self-compassion, CMT showed superiority to CBT
      in reducing depression and anxiety symptoms. CONCLUSION: These findings provide a
      compelling initial argument for the use of CMT as an avenue for addressing
      problems associated with negative affect. Implications, limitations, and future
      directions along this line of research will also be discussed.

PMID- 29473699
TI  - Evaluation of chalcones as inhibitors of glutathione S-transferase.
AB  - Glutathione S-transferases (GSTs) are the superfamily of multifunctional
      detoxification isoenzymes and play an important role in cellular signaling. In
      the present study, potential inhibition effects of chalcones were tested against
      human GST. For this purpose, GST was purified from human erythrocytes with 5.381
      EU?mg-1 specific activity and 51.95% yield using a GSH-agarose affinity
      chromatographic method. The effects of chalcones on in vitro GST activity were
      tested at various concentrations. Ki constants of chalcones were found in the
      range of 7.76-41.93 MUM. According to the results, 4-fluorochalcone showed a
      better inhibitory effect compared with the other compounds. The inhibition
      mechanisms of 2'-hydroxy-4-methoxychalcone and 4-methoxychalcone were
      noncompetitive, whereas the inhibition mechanisms of 4'- hydroxychalcone, 4-
      fluorochalcone, and 4,4'- diflurochalcone were competitive.

PMID- 29473700
TI  - Indirect vs direct assessment of gastric emptying: A randomized crossover trial
      comparing C-isotope breath analysis and MRI.
AB  - BACKGROUND: Indirect methods to assess gastric emptying (GE), such as 13 C breath
      tests (BT), are commonly used. However, BT usually use a sampling time of 4+
      hours. The current study aims to assess the validity of BT for four liquid meals
      differing in physicochemical properties. To this aim, we compared them to MRI GE
      measurements. METHODS: Fifteen healthy males (age 22.6 +/- 2.4 years, BMI 22.6 +/
      1.8 kg/m2 ) participated in a randomized 2 * 2 crossover experiment. Test foods
      were liquid meals, which were either thin/thick and 100/500 kcal, labeled with
      100 mg of 13 C-octanoate. GE was measured with MRI and assessed by 13 C recovery
      from breath. Participants were scanned every 10 minutes and at six time points
      breath samples were collected up to t = 90 minutes. Two curves were fitted to the
      data to estimate emptying halftime (t50 Ghoos and t50 Bluck ). T50 times were
      ranked per participant and compared between methods. KEY RESULTS: On average, MRI
      and BT showed similar t50 rankings for the four liquid meals. In comparison to
      MRI, t50 Ghoos overestimated, while t50 Bluck underestimated GE time. Moreover,
      more viscous foods were overestimated. In most participants individual t50 time
      rankings differed significantly between methods. CONCLUSIONS & INFERENCES: BT can
      assess relative emptying differences on group level and collecting breath data
      for 90 minutes constitutes a lower burden for participants and the research
      facility. However, BT has severe shortcomings compared to MRI for individual GE
      assessment. Notably, food matrix effects should be considered when interpreting
      the results of BT.

PMID- 29473701
TI  - Antibody Epitope of Human alpha-Galactosidase A Revealed by Affinity Mass
      Spectrometry: A Basis for Reversing Immunoreactivity in Enzyme Replacement
      Therapy of Fabry Disease.
AB  - alpha-Galactosidase (alphaGal) is a lysosomal enzyme that hydrolyses the terminal
      alpha-galactosyl moiety from glycosphingolipids. Mutations in the encoding genes
      for alphaGal lead to defective or misfolded enzyme, which results in substrate
      accumulation and subsequent organ dysfunction. The metabolic disease caused by a
      deficiency of human alpha-galactosidase A is known as Fabry disease or Fabry
      Anderson disease, and it belongs to a larger group known as lysosomal storage
      diseases. An effective treatment for Fabry disease has been developed by enzyme
      replacement therapy (ERT), which involves infusions of purified recombinant
      enzyme in order to increase enzyme levels and decrease the amounts of accumulated
      substrate. However, immunoreactivity and IgG antibody formation are major,
      therapy-limiting, and eventually life-threatening complications of ERT. The
      present study focused on the epitope determination of human alpha-galactosidase A
      against its antibody formed. Here we report the identification of the epitope of
      human alphaGal(309-332) recognized by a human monoclonal anti-alphaGal antibody,
      using a combination of proteolytic excision of the immobilized immune complex and
      surface plasmon resonance biosensing mass spectrometry. The epitope peptide,
      alphaGal(309-332), was synthesized by solid-phase peptide synthesis.
      Determination of its affinity by surface plasmon resonance analysis revealed a
      high binding affinity for the antibody (KD =39*10-9  m), which is nearly
      identical to that of the full-length enzyme (KD =16*10-9  m). The proteolytic
      excision affinity mass spectrometry method is shown here to be an efficient tool
      for epitope identification of an immunogenic lysosomal enzyme. Because the full
      length alphaGal and the antibody epitope showed similar binding affinities, this
      provides a basis for reversing immunogenicity upon ERT by: 1) treatment of
      patients with the epitope peptide to neutralize antibodies, or 2) removal of
      antibodies by apheresis, and thus significantly improving the response to ERT.

PMID- 29473702
TI  - Dual C(sp3 )-H Bond Functionalization of N-Heterocycles through Sequential
      Visible-Light Photocatalyzed Dehydrogenation/[2+2] Cycloaddition Reactions.
AB  - Herein we describe a mild method for the dual C(sp3 )-H bond functionalization of
      saturated nitrogen-containing heterocycles through a sequential visible-light
      photocatalyzed dehydrogenation/[2+2] cycloaddition procedure. As a complementary
      approach to the well-established use of iminium ion and alpha-amino radical
      intermediates, the elusive cyclic enamine intermediates were effectively
      generated by photoredox catalysis under mild conditions and efficiently captured
      by acetylene esters to form a wide array of bicyclic amino acid derivatives, thus
      enabling the simultaneous functionalization of two vicinal C(sp3 )-H bonds.

PMID- 29473703
TI  - Application of case mix index in the allocation of nursing human resources.
AB  - AIM: To investigate the feasibility of the case mix index and compare the
      allocation of nursing human resources between two departments of a hospital with
      different case mix indexes in China. BACKGROUND: The case mix index is used to
      assess the resource allocation of all cases in two departments of a hospital. Its
      values can determine the resource allocation required to diagnose and treat the
      patients. METHODS: Clinical data were obtained from 23 different departments in
      2015 and analysed retrospectively from October to November, 2016. Factors
      influencing the allocation of registered nurses were identified, and balanced
      quantities of patients with different case mix indexes were chosen from two
      departments. Spearman correlation analysis was performed. RESULTS: The per capita
      nursing workload was significant (r = .669, p = .000). The length of hospital
      stay, quantity of nurses, and department case mix index were correlated with the
      nursing workload (t = 4.211, p = .000; t = 2.962, p = .008; t = 2.266, p = .035).
      Education levels (Z = -1.391, p = .164) and the professional titles (Z = -1.832,
      p = .067) of the nurses were not statistically significant, whereas the
      registered nurse level differed between two departments (Z = -2.125, p = .034).
      CONCLUSION: The case management index provides references for the efficient
      allocation of registered nurses in clinical practice.

PMID- 29473704
TI  - Effect of exenatide QW or placebo, both added to titrated insulin glargine, in
      uncontrolled type 2 diabetes: The DURATION-7 randomized study.
AB  - AIMS: To compare the efficacy and safety of adding the glucagon-like peptide-1
      receptor agonist exenatide once weekly (QW) 2 mg or placebo among patients with
      type 2 diabetes who were inadequately controlled despite titrated insulin
      glargine (IG) +/- metformin. METHODS: This multicentre, double-blind study
      (ClinicalTrials.gov identifier: NCT02229383) randomized (1:1) patients with
      persistent hyperglycaemia after an 8-week titration phase (glycated haemoglobin
      [HbA1c] 7.0%-10.5% [53-91 mmol/mol]) to exenatide QW or placebo. The primary
      endpoint was HbA1c change from baseline to week 28. Secondary endpoints included
      body weight, 2-hour postprandial glucose, and mean daily IG dose. RESULTS: Of 464
      randomized patients (mean: age, 58 years; HbA1c, 8.5% [69 mmol/mol]; diabetes
      duration, 11.3 years), 91% completed 28 weeks. Exenatide QW + IG vs placebo + IG
      significantly reduced HbA1c (least-squares mean difference, -0.73% [-8.0
      mmol/mol]; 95% confidence interval, -0.93%, -0.53% [-10.2, -5.8 mmol/mol]; P <
      .001; final HbA1c, 7.55% [59 mmol/mol] and 8.24% [67 mmol/mol], respectively);
      body weight (-1.50 kg; -2.17, -0.84; P < .001); and 2-hour postprandial glucose (
      1.52 mmol/L [-27.5 mg/dL]; -2.15, -0.90 [-38.7, -16.2]; P < .001). Significantly
      more exenatide QW + IG-treated patients vs placebo + IG-treated patients reached
      HbA1c <7.0% (<53 mmol/mol) (32.5% vs 7.4%; P < .001); daily IG dose increased by
      2 and 4 units, respectively. Gastrointestinal and injection-site adverse events
      were more frequent with exenatide QW + IG (15.1% and 7.8%, respectively) than
      with placebo + IG (10.8% and 3.0%, respectively); hypoglycaemia incidence was
      similar between the exenatide QW + IG (29.7%) and placebo + IG (29.0%) groups,
      with no major hypoglycaemic events. CONCLUSIONS: Among patients with inadequate
      glycaemic control, exenatide QW significantly improved glucose control and
      decreased body weight, without increased hypoglycaemia or unexpected safety
      findings.

PMID- 29473706
TI  - The influence of need for cognitive closure on the attention-recognition stage of
      preventive coping.
AB  - The current study explored the influence of need for cognitive closure (NFCC) on
      preventive coping via its effects on the attention-recognition stage and sought
      to determine whether this influence was moderated by individuals' existing
      knowledge. An experiment involving 90 university students used the vignette
      reading paradigm to explore the relationships between NFCC, attention and
      preventive coping behaviour. The results indicated that when preventive coping
      situations were consistent with participants' previous knowledge, people with
      high, relative to low, NFCC were more inclined to use preventive coping
      strategies. As a stage of preventive coping, gaining awareness of potential
      stressors mediated the relationship between NFCC and preventive coping. However,
      when coping situations were inconsistent with participants' knowledge, the
      relationship between NFCC and preventive coping was non-significant.

PMID- 29473705
TI  - Alpha-1 antitrypsin treatment of new-onset type 1 diabetes: An open-label, phase
      I clinical trial (RETAIN) to assess safety and pharmacokinetics.
AB  - OBJECTIVE: To determine the safety and pharmacokinetics of alpha-1 antitrypsin
      (AAT) in adults and children. RESEARCH DESIGN AND METHODS: Short-term AAT
      treatment restores euglycemia in the non-obese mouse model of type 1 diabetes. A
      phase I multicenter study in 16 subjects with new-onset type 1 diabetes studied
      the safety and pharmacokinetics of Aralast NP (AAT). This open-label, dose
      escalation study enrolled 8 adults aged 16 to 35 years and 8 children aged 8 to
      15 years within 100 days of diagnosis, to receive 12 infusions of AAT: a low dose
      of 45 mg/kg weekly for 6 weeks, followed by a higher dose of 90 mg/kg for 6
      weeks. RESULTS: C-peptide secretion during a mixed meal, hemoglobin A1c (HbA1c),
      and insulin usage remained relatively stable during the treatment period. At 72
      hours after infusion of 90 mg/kg, mean levels of AAT fell below 2.0 g/L for 7 of
      15 subjects. To identify a plasma level of AAT likely to be therapeutic,
      pharmacodynamic ex vivo assays were performed on fresh whole blood from adult
      subjects. Polymerase chain reaction (PCR) analyses were performed on inhibitor of
      IKBKE, NOD1, TLR1, and TRAD gene expression, which are important for activation
      of nuclear factor-kappaB (NF-kappaB) and apoptosis pathways. AAT suppressed
      expression dose-dependently; 50% inhibition was achieved in the 2.5 to 5.0 mg/mL
      range. CONCLUSIONS: AAT was well tolerated and safe in subjects with new-onset
      type 1 diabetes. Weekly doses of AAT greater than 90 mg/kg may be necessary for
      an optimal therapeutic effect.

PMID- 29473709
TI  - Efficacy and safety of canagliflozin as add-on therapy to a glucagon-like peptide
      1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52-week,
      open-label, phase IV study.
AB  - Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1
      receptor agonists (GLP-1RAs) are antihyperglycaemic agents with weight-lowering
      effects. The efficacy and safety of the SGLT2 inhibitor canagliflozin as add-on
      therapy in Japanese patients with type 2 diabetes mellitus (T2DM) and inadequate
      glycaemic control with a GLP-1RA (>=12 weeks) were evaluated in this phase IV
      study. Patients received canagliflozin 100 mg once daily for 52 weeks. Efficacy
      endpoints included change in glycated haemoglobin (HbA1c), fasting plasma glucose
      (FPG), body weight, systolic blood pressure (SBP) and HDL cholesterol from
      baseline to week 52. Safety endpoints included adverse events (AEs),
      hypoglycaemia and laboratory tests. Of the 71 patients treated with
      canagliflozin, 63 completed the study. At 52 weeks, HbA1c was significantly
      reduced from baseline (-0.70%; paired t test, P < .001). Significant changes were
      also observed in FPG (-34.7 mg/dL), body weight (-4.46%), SBP (-7.90 mm Hg), and
      HDL cholesterol (7.60%; all P < .001). The incidence of AEs, adverse drug
      reactions and hypoglycaemia was 71.8%, 32.4% and 9.9%, respectively. All
      hypoglycaemic events were mild. These findings suggest that the long-term
      combination of canagliflozin with a GLP-1RA is effective and well tolerated in
      Japanese patients with T2DM.

PMID- 29473710
TI  - What is an ORCID iD and Why Would You Want One?

PMID- 29473711
TI  - SDG721 and SDG705 are required for rice growth.
AB  - H3K4me3 plays important roles in development, transcription, and environmental
      responses. Here, we report that SDG721 (SET-domain group protein 721) and SDG705
      are involved in regulating rice development. SDG721 and SDG705 encode TRITHORAX
      like proteins, which appear to modulate H3K4 methylation levels. Loss of SDG721
      and SDG705 function resulted in GA-deficient phenotypes, including semi-dwarfism,
      reduced cell length, and reduced panicle branching. The transcripts levels and
      H3K4me3 levels of GA biosynthesis genes and GA signaling pathway genes were
      downregulated in the sdg721 sdg705 plants. Together, these results suggest that
      SDG721 and SDG705 regulate H3K4 methylation, which is crucial for plant
      development in rice.

PMID- 29473712
TI  - Estimating incident ultraviolet radiation exposure in the northern Gulf of Mexico
      during the Deepwater Horizon oil spill.
AB  - Millions of barrels of oil were released into the Gulf of Mexico following the
      2010 explosion of the Deepwater Horizon oil rig. Polycyclic aromatic hydrocarbons
      (PAHs) are toxic components of crude oil, which may become more toxic in the
      presence of ultraviolet (UV) radiation, a phenomenon known as photo-induced
      toxicity. The Deepwater Horizon spill impacted offshore and estuarine sites,
      where biota may be co-exposed to UV and PAHs. Penetration of UV into the water
      column is affected by site-specific factors. Therefore, measurements and/or
      estimations of UV are necessary when one is assessing the risk to biota posed by
      photo-induced toxicity. We describe how estimates of incident UV were determined
      for the area impacted by the Deepwater Horizon oil spill, using monitoring data
      from radiometers near the spill, in conjunction with reference spectra
      characterizing the composition of solar radiation. Furthermore, we provide UV
      attenuation coefficients for both near- and offshore sites in the Gulf of Mexico.
      These estimates are specific to the time and location of the spill, and fall
      within the range of intensities utilized during photo-induced toxicity tests
      performed in support of the Deepwater Horizon Natural Resource Damage Assessment
      (NRDA). These data further validate the methodologies and findings of
      phototoxicity tests included in the Deepwater Horizon NRDA, while underscoring
      the importance of considering UV exposure when assessing possible risks following
      oil spills. Environ Toxicol Chem 2018;37:1679-1687. (c) 2018 SETAC.

PMID- 29473714
TI  - Deficient invariant natural killer T cells had impaired regulation on
      osteoclastogenesis in myeloma bone disease.
AB  - Recent research showed that invariant natural killer T (iNKT) cells take part in
      the regulation of osteoclastogenesis. While the role of iNKT cells in myeloma
      bone disease (MBD) remains unclear. In our study, the quantity of iNKT cells and
      the levels of cytokines produced by them were measured by flow cytometry. iNKT
      cells and osteoclasts were induced from peripheral blood mononuclear cells after
      activation by alpha-GalCer or RANKL in vitro. Then, gene expressions and the
      levels of cytokines were determined by RT-PCR and ELISA, respectively. The
      results showed that the quantity of iNKT and production of IFN-gamma by iNKT
      cells were significantly decreased in newly diagnosed MM (NDMM), and both
      negatively related with severity of bone disease. Then, the osteoclasts from
      healthy controls were cultured in vitro and were found to be down-regulated after
      alpha-GalCer-stimulated, while there was no significant change with or without
      alpha-GalCer in NDMM patients, indicating that the regulation of
      osteoclastogenesis by iNKT cells was impaired. Furthermore, the inhibition of
      osteoclastogenesis by iNKT cells was regulated by IFN-gamma production, which
      down-regulated osteoclast-associated genes. In conclusion, the role of alpha
      GalCer-stimulated iNKT cells in regulation of osteoclastogenesis was impaired in
      MBD, as a result of iNKT cell dysfunction.

PMID- 29473716
TI  - Magneto-Mechanical Surfaces Design.
AB  - Magneto-mechanically active surfaces (MMAS) represent a new family of nano/micro
      structured surfaces in which motion is induced by an external magnetic field.
      Under the name of "artificial cilia", "biomimetic cilia", "magnetic actuated
      patterns", "nanopillars", etc., published works in this area continue their quick
      growth in number. Notwithstanding their potential application in microfluidic,
      chemical sensors, catalytic processes and microelectronics to increase device
      perfomances, there is still a lot to do in the development of these materials.
      Improvement and optimization of the performance of these structures are essential
      tasks in order to fulfil their complete development. Along this article, a
      critical review involving the main aspects in the design of the patterned
      nanocomposites will be presented.

PMID- 29473715
TI  - Multinational Qualitative Research Study Exploring the Patient Experience of
      Raynaud's Phenomenon in Systemic Sclerosis.
AB  - OBJECTIVE: Raynaud's phenomenon (RP) is the most common manifestation of systemic
      sclerosis (SSc). RP is an episodic phenomenon, not easily assessed in the clinic,
      leading to reliance on self-report. A thorough understanding of the patient
      experience of SSc-RP is essential to ensuring that patient-reported outcome (PRO)
      instruments capture domains important to the target patient population. We report
      the findings of an international qualitative research study investigating the
      patient experience of SSc-RP. METHODS: Focus groups of SSc patients were
      conducted across 3 scleroderma centers in the US and UK, using a topic guide and
      a priori purposive sampling framework devised by qualitative researchers, SSc
      patients, and SSc experts. Focus groups were audio recorded, transcribed,
      anonymized, and analyzed using inductive thematic analysis. Focus groups were
      conducted until thematic saturation was achieved. RESULTS: Forty SSc patients
      participated in 6 focus groups conducted in Bath (UK), New Orleans (Louisiana),
      and Pittsburgh (Pennsylvania). Seven major themes were identified that
      encapsulate the patient experience of SSc-RP: physical symptoms, emotional
      impact, triggers and exacerbating factors, constant vigilance and self
      management, impact on daily life, uncertainty, and adaptation. The
      interrelationship of the 7 constituent themes can be arranged within a conceptual
      map of SSc-RP. CONCLUSION: We have explored the patient experience of SSc-RP in a
      diverse and representative SSc cohort and identified a complex interplay of
      experiences that result in significant impact. Work to develop a novel PRO
      instrument for assessing the severity and impact of SSc-RP, comprising
      domains/items grounded in the patient experiences of SSc-RP identified in this
      study, is underway.

PMID- 29473718
TI  - In response to Manuscript AJRI 01-18-016 entitled "Regulatory T cells, natural
      killer cells and obesity in patients with gestational diabetes mellitus"-Kawada
      T.

PMID- 29473719
TI  - Diabetic Macular Edema: Current Understanding, Pharmacologic Treatment Options,
      and Developing Therapies.
AB  - Diabetic retinopathy and diabetic macular edema comprise a major source of visual
      disability throughout the developed world. The etiology and pathogenesis of
      macular edema is intricate and multifactorial, in which the hyperglycemic state
      in diabetes induces a microangiopathy. Through several inflammatory and vasogenic
      mediators, including vascular endothelial growth factor (VEGF) upregulation and
      inflammatory cytokines and chemokines, pathologic changes are induced in the
      vascular endothelium triggering breakdown of the blood retinal barrier, causing
      extravasation of fluid into the extracellular space and manifesting clinically as
      macular edema, resulting in visual loss. The advent of medications targeting the
      VEGF pathway has led to great clinical improvements compared with the previous
      standard of care of laser therapy alone, as shown in studies such as RISE, RIDE,
      VIVID, VISTA, and DRCR. However, analyses have shown that many patients have
      inadequate response or are nonresponders to anti-VEGF therapy, demonstrating the
      need for additional therapies to more comprehensively treat this disease.
      Although corticosteroid treatments and implants have demonstrated some efficacy
      in adjunctive and supplemental treatment, the need to more adequately treat
      macular edema remains. Our knowledge of diabetic macular edema continues to grow,
      leading to new currently available and emerging pharmacotherapies to further
      enhance our treatment and restore vision in those affected by diabetic macular
      edema. This review will discuss the pathogenesis of diabetic macular edema and
      the pharmacologic therapies available for its treatment, including anti-VEGF,
      steroids, and newer therapies still in development, such as angiopoietin
      antagonists, Tie2 agonists, kallikrein inhibitors, interleukin inhibitors, and
      others.

PMID- 29473717
TI  - Interventions for paracetamol (acetaminophen) overdose.
AB  - BACKGROUND: Paracetamol (acetaminophen) is the most widely used non-prescription
      analgesic in the world. Paracetamol is commonly taken in overdose either
      deliberately or unintentionally. In high-income countries, paracetamol toxicity
      is a common cause of acute liver injury. There are various interventions to treat
      paracetamol poisoning, depending on the clinical status of the person. These
      interventions include inhibiting the absorption of paracetamol from the
      gastrointestinal tract (decontamination), removal of paracetamol from the
      vascular system, and antidotes to prevent the formation of, or to detoxify,
      metabolites. OBJECTIVES: To assess the benefits and harms of interventions for
      paracetamol overdosage irrespective of the cause of the overdose. SEARCH METHODS:
      We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (January
      2017), CENTRAL (2016, Issue 11), MEDLINE (1946 to January 2017), Embase (1974 to
      January 2017), and Science Citation Index Expanded (1900 to January 2017). We
      also searched the World Health Organization International Clinical Trials
      Registry Platform and ClinicalTrials.gov database (US National Institute of
      Health) for any ongoing or completed trials (January 2017). We examined the
      reference lists of relevant papers identified by the search and other published
      reviews. SELECTION CRITERIA: Randomised clinical trials assessing benefits and
      harms of interventions in people who have ingested a paracetamol overdose. The
      interventions could have been gastric lavage, ipecacuanha, or activated charcoal,
      or various extracorporeal treatments, or antidotes. The interventions could have
      been compared with placebo, no intervention, or to each other in differing
      regimens. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted data from the included trials. We used fixed-effect and random-effects
      Peto odds ratios (OR) with 95% confidence intervals (CI) for analysis of the
      review outcomes. We used the Cochrane 'Risk of bias' tool to assess the risks of
      bias (i.e. systematic errors leading to overestimation of benefits and
      underestimation of harms). We used Trial Sequential Analysis to control risks of
      random errors (i.e. play of chance) and GRADE to assess the quality of the
      evidence and constructed 'Summary of findings' tables using GRADE software. MAIN
      RESULTS: We identified 11 randomised clinical trials (of which one acetylcysteine
      trial was abandoned due to low numbers recruited), assessing several different
      interventions in 700 participants. The variety of interventions studied included
      decontamination, extracorporeal measures, and antidotes to detoxify paracetamol's
      toxic metabolite; which included methionine, cysteamine, dimercaprol, or
      acetylcysteine. There were no randomised clinical trials of agents that inhibit
      cytochrome P-450 to decrease the activation of the toxic metabolite N-acetyl-p
      benzoquinone imine.Of the 11 trials, only two had two common outcomes, and hence,
      we could only meta-analyse two comparisons. Each of the remaining comparisons
      included outcome data from one trial only and hence their results are presented
      as described in the trials. All trial analyses lack power to access efficacy.
      Furthermore, all the trials were at high risk of bias. Accordingly, the quality
      of evidence was low or very low for all comparisons. Interventions that prevent
      absorption, such as gastric lavage, ipecacuanha, or activated charcoal were
      compared with placebo or no intervention and with each other in one four-armed
      randomised clinical trial involving 60 participants with an uncertain
      randomisation procedure and hence very low quality. The trial presented results
      on lowering plasma paracetamol levels. Activated charcoal seemed to reduce the
      absorption of paracetamol, but the clinical benefits were unclear. Activated
      charcoal seemed to have the best risk:benefit ratio among gastric lavage,
      ipecacuanha, or supportive treatment if given within four hours of ingestion.
      There seemed to be no difference between gastric lavage and ipecacuanha, but
      gastric lavage and ipecacuanha seemed more effective than no treatment (very low
      quality of evidence). Extracorporeal interventions included charcoal
      haemoperfusion compared with conventional treatment (supportive care including
      gastric lavage, intravenous fluids, and fresh frozen plasma) in one trial with 16
      participants. The mean cumulative amount of paracetamol removed was 1.4 g. One
      participant from the haemoperfusion group who had ingested 135 g of paracetamol,
      died. There were no deaths in the conventional treatment group. Accordingly, we
      found no benefit of charcoal haemoperfusion (very low quality of evidence).
      Acetylcysteine appeared superior to placebo and had fewer adverse effects when
      compared with dimercaprol or cysteamine. Acetylcysteine superiority to methionine
      was unproven. One small trial (low quality evidence) found that acetylcysteine
      may reduce mortality in people with fulminant hepatic failure (Peto OR 0.29, 95%
      CI 0.09 to 0.94). The most recent randomised clinical trials studied different
      acetylcysteine regimens, with the primary outcome being adverse events. It was
      unclear which acetylcysteine treatment protocol offered the best efficacy, as
      most trials were underpowered to look at this outcome. One trial showed that a
      modified 12-hour acetylcysteine regimen with a two-hour acetylcysteine 100 mg/kg
      bodyweight loading dose was associated with significantly fewer adverse reactions
      compared with the traditional three-bag 20.25-hour regimen (low quality of
      evidence). All Trial Sequential Analyses showed lack of sufficient power.
      Children were not included in the majority of trials. Hence, the evidence
      pertains only to adults. AUTHORS' CONCLUSIONS: These results highlight the
      paucity of randomised clinical trials comparing different interventions for
      paracetamol overdose and their routes of administration and the low or very low
      level quality of the evidence that is available. Evidence from a single trial
      found activated charcoal seemed the best choice to reduce absorption of
      paracetamol. Acetylcysteine should be given to people at risk of toxicity
      including people presenting with liver failure. Further randomised clinical
      trials with low risk of bias and adequate number of participants are required to
      determine which regimen results in the fewest adverse effects with the best
      efficacy. Current management of paracetamol poisoning worldwide involves the
      administration of intravenous or oral acetylcysteine which is based mainly on
      observational studies. Results from these observational studies indicate that
      treatment with acetylcysteine seems to result in a decrease in morbidity and
      mortality, However, further evidence from randomised clinical trials comparing
      different treatments are needed.

PMID- 29473720
TI  - Maybe it is not a goal that matters: a report from a physical activity
      intervention in youth.
AB  - BACKGROUND: Decline in physical activity (PA), specifically in adolescents raises
      concerns. Setting goals and strategies are often used to increase the level of
      moderate-to-vigorous physical activity (MVPA), recently introducing also modern
      technological devices for achieving different goals. The aim of this study was to
      investigate the effectiveness of two different goal strategies in increasing PA
      of youth. It was expected that there would be positive relationships between
      support and goal strategy which would contribute to increase MVPA. Classmate and
      teacher support scales were used to evaluate support in physical education (PE)
      classes. Activity trackers were used to count daily steps. METHODS: Data were
      collected from 65 late adolescents, divided into two groups: "Goal" (group 1) and
      "Do your best" (group 2) set with different step goals and strategies.
      Differences between the terms were tested. To compare MVPA levels with the
      different level of support they received in girls and boys, a two-way ANOVA was
      used. RESULTS: There was a difference noticed in teacher support between the
      genders in all the two groups in favor of boys. Boys with low teacher support in
      group 1 indicated a higher level of MVPA. In group 2 when teacher support was
      high girls reported the highest level of MVPA. CONCLUSIONS: This study has shown
      that in terms of MVPA teacher support is more efficient than a goal strategy. The
      results highlight the importance of perceived teacher support for motivation in
      PA and pointed at PE teachers as the agents of behavior change, specifically in
      girls.

PMID- 29473721
TI  - Enhancing dietary practices, general nutrition knowledge and body composition of
      a female International Rugby Union player incorporating smartphone application
      technology.

PMID- 29473722
TI  - Nurses Writing about Psychiatric Nurses' Involvement in Killings during the Nazi
      Era: A Preliminary Discourse Analysis.
AB  - Nurses actively killed people in Nazi Europe between 1939 and 1945. The so-called
      'science of eugenics' underpinned Nazi ideology, used to further the Nazi racist
      agenda. Edicts sanctioned selection and medically supervised killing of people,
      and nurses, principally in mental hospitals, participated in the killing of
      between 100-300 thousand patients. Erroneously termed 'euthanasia', there were
      three phases: the initial programme involving children, the T4 adult programme,
      and 'wild euthanasia'. Unofficial killings also took place before 1939. This
      paper uses discourse analysis to map and analyse published texts which explore
      the role of nurses in Nazi Germany. The aim is to identify its characteristics as
      a body of literature, to note strengths and weaknesses, emphases and silences,
      and to note aspects that need further exploration. It acknowledges that how these
      events are to be understood and represented in contemporary discourse constitutes
      a significant problem for historians of nursing.

PMID- 29473723
TI  - Australia: The 'Good' Genocide Perpetrator?
AB  - In 1949, federal parliamentarians were indignant when asked to ratify the United
      Nations Convention on the Prevention and Punishment of the Crime of Genocide
      (hereafter, UNGC). We could not in any way be associated with 'the unthinkable'
      crime, senior members claimed, because we are 'a moral people' with a 'clean
      record'. This essay assesses the 'decent' Australian democrats who, as the
      indelible records show, set out to kill the Aboriginal people they deemed
      'vermin' and then later, decided to engage in a eugenicist fantasy to rid
      Australia of Aborigines by intermarriage or, failing that, forcibly removing
      their children in large numbers. The colonial frontier killings were justified as
      'dispersing kangaroos'. Child removals were done 'in their best interests'. This
      essay attempts to gain an insight into the mindset of those who did commit 'the
      unthinkable' crime of genocide: killing, removal of children, and 'causing
      serious bodily and mental harm'. Subsequent policies infantalised the Aboriginal
      and Islander population and denied them basic human rights.

PMID- 29473724
TI  - The Contemporary Significance of the Holocaust for Australian Psychiatry.
AB  - In this paper we survey briefly the components of the Holocaust directly relevant
      to the psychiatric profession and identify the main themes of relevance to
      contemporary psychiatry. The 'euthanasia' program; the persecution of lesbian,
      gay, bisexual, transgender, and intersex (LGBTI) citizens; and the complex
      relationship between the psychiatric profession and Nazi state are the main
      themes to emerge from this survey. We then compare this period with key themes in
      the history of Australian psychiatry and link these themes to some of the
      contemporary ethical challenges the profession faces.

PMID- 29473725
TI  - Lipid Shell-Enveloped Polymeric Nanoparticles with High Integrity of Lipid Shells
      Improve Mucus Penetration and Interaction with Cystic Fibrosis-Related Bacterial
      Biofilms.
AB  - Nanoparticle (NP) mediated drug delivery into viscous biomatrices, e.g., mucus
      and bacterial biofilms, is challenging. Lipid shell-enveloped polymeric NPs
      (Lipid@NPs), composed of a polymeric NP core coated with a lipid shell, represent
      a promising alternative to the current delivery systems. Here, we describe the
      facile methods to prepare Lipid@NPs with high integrity of lipid shells and
      demonstrate the potential of Lipid@NPs in an effective mucus penetration and
      interaction with cystic fibrosis-related bacterial biofilms. Lipid shell
      enveloped polystyrene NPs with high integrity of lipid shells ( cLipid@PSNPs)
      were prepared by using an electrostatically mediated layer-by-layer approach,
      where the model polystyrene NPs (PSNPs) were first modified with positively
      charged poly-l-lysine (PLL) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP),
      followed by subsequent fusion with zwitterionic, PEGylated small unilamellar
      vesicles (SUVs). The interaction of the PSNPs with SUVs was significantly
      enhanced by modifying the PSNPs with PLL and DOTAP, which eventually resulted in
      the formation of cLipid@PSNPs, i.e., Lipid@PLL-PSNPs and Lipid@DOTAP-PSNPs.
      Improved mucus-penetrating property of cLipid@PSNPs was demonstrated by quartz
      crystal microbalance with dissipation monitoring measurements. Furthermore,
      fluorescence resonance energy transfer measurements showed that the interaction
      of the cLipid@PSNPs with bacterial biofilms was significantly promoted. In
      conclusion, we prepared cLipid@PSNPs via an electrostatically mediated layer-by
      layer approach. Our results suggest that the integrity of the lipid envelopes is
      crucial for enabling the diffusion of Lipid@PSNPs into the mucus layer and
      promoting the interaction of Lipid@PSNPs with a bacterial biofilm.

PMID- 29473726
TI  - Defect Sites-Rich Porous Carbon with Pseudocapacitive Behaviors as an Ultrafast
      and Long-Term Cycling Anode for Sodium-Ion Batteries.
AB  - Room-temperature sodium-ion batteries have been regarded as promising candidates
      for grid-scale energy storage due to their low cost and the wide distribution of
      sodium sources. The main scientific challenge for their practical application is
      to develop suitable anodes with long-term cycling stability and high rate
      capacity. Here, novel hierarchical three-dimensional porous carbon materials are
      synthesized through an in situ template carbonization process. Electrochemical
      examination demonstrates that carbonization temperature is a key factor that
      affects Na+-ion-storage performance, owing to the consequent differences in
      surface area, pore volume, and degree of crystallinity. The sample obtained at
      600  degrees C delivers the best sodium-storage performance, including long-term
      cycling stability (15 000 cycles) and high rate capacity (126 mAh g-1 at 20 A g
      1). Pseudocapacitive behavior in the Na+-ion-storage process has been confirmed
      and studied via cyclic voltammetry. Full cells based on the porous carbon anode
      and Na3V2(PO4)3-C cathode also deliver good cycling stability (400 cycles).
      Porous carbon, combining the merits of high energy density and extraordinary
      pseudocapacitive behavior after cycling stability, can be a promising replacement
      for battery/supercapacitors hybrid and suggest a design strategy for new energy
      storage materials.

PMID- 29473727
TI  - High Capacity and Superior Cyclic Performances of All-Solid-State Lithium
      Batteries Enabled by a Glass-Ceramics Solo.
AB  - By using highly Li-ion conductive 78Li2S-22P2S5 glass-ceramic (7822gc) as both
      the electrolyte and active material in the composite cathode obtained via ball
      milling the 7822gc with multiple carbons, a kind of monolithic all-solid-state
      batteries were prepared with a lithium-indium foil as the anode. Such 7822gc
      based monolithic batteries present stable discharge capacity of 480.3 mA h g-1 at
      0.176 mA cm-2 after 60 cycles, which is three times larger than that of the
      previous work, with the highest capacity obtained so far among all attempts of
      using sulfide electrolytes as the active materials. High capacity retention of
      90.6% and Coulombic efficiency of higher than 99% with high active material
      loading of 7 mg cm-2 were also obtained. X-ray photoelectron spectroscopy was
      used to reveal the electrochemical reaction mechanisms in the 7822gc cathode.

PMID- 29473728
TI  - Highly Ordered Hierarchical Pt and PtNi Nanowire Arrays for Enhanced
      Electrocatalytic Activity toward Methanol Oxidation.
AB  - Highly ordered hierarchical Pt and PtNi nanowire arrays were prepared using CdS
      hierarchical nanowire arrays (HNWAs) as sacrificial templates and demonstrated
      high electrochemical active surface areas. For the resulting Pt HNWAs sample, the
      peak current for methanol oxidation at +0.74 V was almost 1 order of magnitude
      higher than that of Pt solid nanowire arrays prepared in a similar manner but
      without the use of CdS template, and the addition of a Ni cocatalyst effectively
      enhanced the tolerance against CO poisoning. The results demonstrated that highly
      ordered Pt and PtNi HNWAs may be exploited as promising anode catalysts in the
      application of direct methanol fuel cells.

PMID- 29473729
TI  - Streptomyces wadayamensis MppP is a PLP-Dependent Oxidase, Not an Oxygenase.
AB  - The PLP-dependent l-arginine hydroxylase/deaminase MppP from Streptomyces
      wadayamensis (SwMppP) is involved in the biosynthesis of l-enduracididine, a
      nonproteinogenic amino acid found in several nonribosomally produced peptide
      antibiotics. SwMppP uses only PLP and molecular oxygen to catalyze a 4-electron
      oxidation of l-arginine to form a mixture of 2-oxo-4(S)-hydroxy-5
      guanidinovaleric acid and 2-oxo-5-guanidinovaleric acid. Steady-state kinetics
      analysis in the presence and absence of catalase shows that one molecule of
      peroxide is formed for every molecule of dioxygen consumed in the reaction.
      Moreover, for each molecule of 2-oxo-4(S)-hydroxy-5-guanidinovaleric acid
      produced, two molecules of dioxygen are consumed, suggesting that both the 4
      hydroxy and 2-keto groups are derived from water. This was confirmed by running
      the reactions using either [18]O2 or H2[18]O and analyzing the products by ESI
      MS. Incorporation of [18]O was only observed when the reaction was performed in
      H2[18]O. Crystal structures of SwMppP with l-arginine, 2-oxo-4(S)-hydroxy-5
      guanidinovaleric acid, or 2-oxo-5-guanidinovaleric acid bound were determined at
      resolutions of 2.2, 1.9. and 1.8 A, respectively. The structural data show that
      the N-terminal portion of the protein is disordered unless substrate or product
      is bound in the active site, in which case it forms a well-ordered helix that
      covers the catalytic center. This observation suggested that the N-terminal helix
      may have a role in substrate binding and/or catalysis. Our structural and kinetic
      characterizations of N-terminal variants show that the N-terminus is critical for
      catalysis. In light of this new information, we have refined our previously
      proposed mechanism of the SwMppP-catalyzed oxidation of l-arginine.

PMID- 29473730
TI  - Noncatalytic Endosialidase Enables Surface Capture of Small-Cell Lung Cancer
      Cells Utilizing Strong Dendrimer-Mediated Enzyme-Glycoprotein Interactions.
AB  - Enumeration of circulating tumor cells (CTCs) of small-cell lung cancer (SCLC)
      patients has been shown to predict the disease progress and long-term survival.
      Most CTC detection methods rely on epithelial surface markers, such as epithelial
      cell adhesion molecule (EpCAM). However, this marker in SCLC is reported to be
      often downregulated after a variety of phenotypic changes, which impairs the
      reliability of EpCAM-based CTC detections. In this regard, the development of an
      alternative CTC detection method involving different CTC surface markers is in
      demand. In this study, we evaluated, for the first time to our knowledge, the
      feasibility of detecting SCLC CTCs using a noncatalytic endosialidase (EndoN
      Trap, EndoNt). This noncatalytic enzyme was chosen due to its high affinity to
      polysialic acid (polySia), a cell-surface glycan, that is highly expressed by
      SCLC tissue. Furthermore, this enzyme-based system was integrated into our
      dendrimer-mediated CTC capture platform to further enhance the capture efficiency
      via multivalent binding. We found that the EndoNt-immobilized surfaces could
      specifically capture polySia-positive SCLC cells and the binding between SCLC
      cells and EndoNt surfaces was further stabilized by dendrimer-mediated
      multivalent binding. When compared to the EpCAM-based capture, EndoNt
      significantly improved the capture efficiency of polySia-positive SCLC cells
      under flow due to its higher binding affinity (lower dissociation rate
      constants). These findings suggest that this enzyme-based CTC capture strategy
      has the potential to be used as a superior alternative to the commonly used EpCAM
      based methods, particularly for those types of cancer that overexpress polySia.

PMID- 29473731
TI  - In Silico Identification and Experimental Validation of Novel Anti-Alzheimer's
      Multitargeted Ligands from a Marine Source Featuring a "2-Aminoimidazole plus
      Aromatic Group" Scaffold.
AB  - Multitargeting or polypharmacological approaches, looking for single chemical
      entities retaining the ability to bind two or more molecular targets, are a
      potentially powerful strategy to fight complex, multifactorial pathologies.
      Unfortunately, the search for multiligand agents is challenging because only a
      small subset of molecules contained in molecular databases are bioactive and even
      fewer are active on a preselected set of multiple targets. However, collections
      of natural compounds feature a significantly higher fraction of bioactive
      molecules than synthetic ones. In this view, we searched our library of 1175
      natural compounds from marine sources for molecules including a 2
      aminoimidazole+aromatic group motif, found in known compounds active on single
      relevant targets for Alzheimer's disease (AD). This identified two molecules, a
      pseudozoanthoxanthin (1) and a bromo-pyrrole alkaloid (2), which were predicted
      by a computational approach to possess interesting multitarget profiles on AD
      target proteins. Biochemical assays experimentally confirmed their biological
      activities. The two compounds inhibit acetylcholinesterase,
      butyrylcholinesterase, and beta-secretase enzymes in high- to sub-micromolar
      range. They are also able to prevent and revert beta-amyloid (Abeta) aggregation
      of both Abeta1-40 and Abeta1-42 peptides, with 1 being more active than 2.
      Preliminary in vivo studies suggest that compound 1 is able to restore
      cholinergic cortico-hippocampal functional connectivity.

PMID- 29473732
TI  - Innovative Cryopreservation Process Using a Modified Core/Shell Cell-Printing
      with a Microfluidic System for Cell-Laden Scaffolds.
AB  - This work investigated the printability and applicability of a core/shell cell
      printed scaffold for medium-term (for up to 20 days) cryopreservation and
      subsequent cultivation with acceptable cellular activities including cell
      viability. We developed an innovative cell-printing process supplemented with a
      microfluidic channel, a core/shell nozzle, and a low-temperature working stage to
      obtain a cell-laden 3D porous collagen scaffold for cryopreservation. The 3D
      porous biomedical scaffold consisted of core/shell struts with a cell-laden
      collagen-based bioink/dimethyl sulfoxide mixture in the core region and an
      alginate/poly(ethylene oxide) mixture in the shell region. Following 2 weeks of
      cryopreservation, the cells (osteoblast-like cells or human adipose stem cells)
      in the scaffold showed good viability (over 90%), steady growth, and
      mineralization similar to those of a control scaffold fabricated using a
      conventional cell-printing process without cryopreservation. We believe that
      these results are attributable to the optimized fabrication processes the cells
      underwent, including safe freezing/thawing processes. On the basis of these
      results, this fabrication process has great potential for obtaining core/shell
      cell-laden collagen scaffolds for cryopreservation, which have various tissue
      engineering applications.

PMID- 29473733
TI  - alpha-l-Threose Nucleic Acids as Biocompatible Antisense Oligonucleotides for
      Suppressing Gene Expression in Living Cells.
AB  - Because of the chemical simplicity of alpha-l-threose nucleic acid (TNA) and its
      ability to exchange genetic information between itself and RNA, it has attracted
      significant interest as the RNA ancestor. We herein explore the biological
      properties and evaluate the potency of sequence-designed TNA polymers to suppress
      the gene expression in living environments. We found that sequence-specific TNA
      macromolecules exhibit strong affinity and specificity toward the complementary
      RNA targets, are highly biocompatible and nontoxic in a living cell system, and
      readily enter a number of cell lines without using transfecting agents.
      Particularly, TNA exhibited much stronger enzymatic resistance toward fetal
      bovine serum or human serum as compared to traditional antisense
      oligonucleotides, which means that the intrinsic structure of TNA is thoroughly
      resistant to biological degradation. Importantly, the efficacy of the TNA
      molecule with green fluorescent protein (GFP) target sequence (anti-GFP TNAs) as
      antisense agents was first demonstrated in living cells in which these polymers
      revealed high antisense activity in terms of the degree of inhibition of GFP gene
      expression. The GFP gene inhibition studies in HeLa and HEK293 cells characterize
      sequence-controlled TNA as a functional biomaterial and a valuable alternative to
      traditional antisense oligonucleotides such as peptide nucleic acids,
      phosphorodiamidate morpholino oligomers, and locked nucleic acids for a wide
      range of applications in drug discovery and life science research. Additionally,
      we also first reported the cost-efficient approach to synthesize the four TNA
      phosphoramidite monomers using 2-cyanoethyl N, N, N', N'
      tetraisopropylphosphoramidite as a key reagent. Furthermore, by increasing the
      frequency of the deblocking and coupling reactions together with extending their
      reaction time in each synthesis cycle, sequence-controlled TNAs can be easily
      synthesized in a quantitative yield and high purity.

PMID- 29473734
TI  - Ligand Size and Conformation Affect the Behavior of Nanoparticles Coated with in
      Vitro and in Vivo Protein Corona.
AB  - Protein corona is immediately established on the surface of nanoparticles upon
      their introduction into biological milieu. Several studies have shown that the
      targeting efficiency of ligand-modified nanoparticles is attenuated or abolished
      owing to the protein adsorption. Here, transferrin receptor-targeting ligands,
      including LT7 (CHAIYPRH), DT7 (hrpyiahc, all d-form amino acids), and
      transferrin, were used to identify the influence of the ligand size and
      conformation on protein corona formation. The results showed that the targeting
      capacity of ligand-modified nanoparticles was lost after incubation with plasma
      in vitro, whereas it was partially retained after in vivo corona formation.
      Results from sodium dodecyl sulfate polyacrylamide gel electrophoresis and liquid
      chromatography-mass spectrometry revealed the difference in the composition of in
      vitro and in vivo corona, wherein the ligand size and conformation played a
      critical role. Differences were observed in cellular internalization and
      exocytosis profiles on the basis of the ligand and corona source.

PMID- 29473735
TI  - The Use of Ex Vivo Organ Cultures in Tick-Borne Virus Research.
AB  - Each year there are more than 15 000 cases of human disease caused by infections
      with tick-borne viruses (TBVs). These illnesses occur worldwide and can range
      from very mild illness to severe encephalitis and hemorrhagic fever. Although
      TBVs are currently identified as neglected vector-borne pathogens and receive
      less attention than mosquito-borne viruses, TBVs are expanding into new regions,
      and infection rates are increasing. Furthermore, effective vaccines, diagnostic
      tools, and other countermeasures are limited. The application of contemporary
      technologies to TBV infections presents an excellent opportunity to develop
      improved, effective countermeasures. Experimental tick and mammal models of
      infection can be used to characterize determinants of infection, transmission,
      and virulence and to test candidate countermeasures. The use of ex vivo tick
      cultures in TBV research provides a unique way to look at infection in specific
      tick organs. Mammal ex vivo organ slice and, more recently, organoid cultures are
      additional models that can be used to elucidate direct tissue-specific responses
      to infection. These ex vivo model systems are convenient for testing methods
      involving transcript knockdown and small molecules under tightly controlled
      conditions. They can also be combined with in vitro and in vivo studies to tease
      out possible host factors and potential vaccine or therapeutic candidates. In
      this brief perspective, we describe how ex vivo cultures can be combined with
      modern technologies to advance research on TBV infections.

PMID- 29473736
TI  - Improving the Photo-Oxidative Performance of Bi2MoO6 by Harnessing the Synergy
      between Spatial Charge Separation and Rational Co-Catalyst Deposition.
AB  - It has been reported that photogenerated electrons and holes can be directed
      toward specific crystal facets of a semiconductor particle, which is believed to
      arise from the differences in their surface electronic structures, suggesting
      that different facets can act as either photoreduction or photo-oxidation sites.
      This study examines the propensity for this effect to occur in faceted, plate
      like bismuth molybdate (Bi2MoO6), which is a useful photocatalyst for water
      oxidation. Photoexcited electrons and holes are shown to be spatially separated
      toward the {100} and {001}/{010} facets of Bi2MoO6, respectively, by facet
      dependent photodeposition of noble metals (Pt, Au, and Ag) and metal oxides
      (PbO2, MnO x, and CoO x). Theoretical calculations revealed that differences in
      energy levels between the conduction bands and valence bands of the {100} and
      {001}/{010} facets can contribute to electrons and holes being drawn to different
      surfaces of the plate-like Bi2MoO6. Utilizing this knowledge, the photo-oxidative
      capability of Bi2MoO6 was improved by adding an efficient water oxidation co
      catalyst, CoO x, to the system, whereby the extent of enhancement was shown to be
      governed by the co-catalyst location. A greater oxygen evolution occurred when
      CoO x was selectively deposited on the hole-rich {001}/{010} facets of Bi2MoO6
      compared to when CoO x was randomly located across all of the facets. The
      elevated performance exhibited for the selectively loaded CoO x/Bi2MoO6 was
      ascribed to the greater opportunity for hole trapping by the co-catalyst being
      accentuated over other potentially detrimental effects, such as the co-catalyst
      acting as a recombination medium and/or covering reactive sites. The results
      indicate that harnessing the synergy between the spatial charge separation and
      the co-catalyst location on the appropriate facets of plate-like Bi2MoO6 can
      promote its photocatalytic activity.

PMID- 29473737
TI  - Optofluidic Sensor for Inline Hemolysis Detection on Whole Blood.
AB  - Hemolysis is the rupture of red blood cells and constitutes the most common
      reason for unsuitable blood samples in the clinic. To detect hemolysis, one has
      to separate the hemoglobin in blood plasma from that in red blood cells. However,
      current methods entail centrifugation for cell-plasma separation, which is
      complex, time-consuming, and not easy to integrate into point-of-care (PoC)
      systems. Here, we demonstrate an optofluidic sensor composed of nanofilters on an
      optical waveguide, which enables evanescent-wave absorption measurement of
      hemoglobin in plasma with the capability of real-time inline detection on whole
      blood without extra sample preparation like centrifugation. Long-term testing
      with inline integration in a modified, commercial blood gas analyzer shows high
      reliability and repeatability of the measurements even with the presence of
      interference from bilirubin. We envision that the present work has large
      potential in improving diagnosis quality by enabling PoC hemolysis detection in
      blood gas analyzers and can also lend unique sensing capabilities to other
      applications dealing with complex turbid media.

PMID- 29473738
TI  - Surface Charge Modulates Protein-Protein Interactions in Physiologically Relevant
      Environments.
AB  - Protein-protein interactions are fundamental to biology yet are rarely studied
      under physiologically relevant conditions where the concentration of
      macromolecules can exceed 300 g/L. These high concentrations cause cosolute
      complex contacts that are absent in dilute buffer. Understanding such
      interactions is important because they organize the cellular interior. We used
      19F nuclear magnetic resonance, the dimer-forming A34F variant of the model
      protein GB1, and the cosolutes bovine serum albumin (BSA) and lysozyme to assess
      the effects of repulsive and attractive charge-charge dimer-cosolute interactions
      on dimer stability. The interactions were also manipulated via charge-change
      variants and by changing the pH. Charge-charge repulsions between BSA and GB1
      stabilize the dimer, and the effects of lysozyme indicate a role for attractive
      interactions. The data show that chemical interactions can regulate the strength
      of protein-protein interactions under physiologically relevant crowded conditions
      and suggest a mechanism for tuning the equilibrium thermodynamics of protein
      protein interactions in cells.

PMID- 29473739
TI  - Mechanistic Implications of the Deamination of TDP-4-amino-4-deoxy-d-fucose
      Catalyzed by the Radical SAM Enzyme DesII.
AB  - DesII is a radical SAM lyase that catalyzes a deamination reaction during the
      biosynthesis of desosamine in Streptomyces venezuelae. Competing mechanistic
      hypotheses for this radical-mediated reaction are differentiated according to
      whether a 1,2-migration takes place and the timing of proton abstraction
      following generation of a substrate alpha-hydroxyalkyl radical intermediate. In
      this study, the deuterated C4 epimer of the natural substrate, TDP-4-amino-4
      deoxy-d-[3-2H]fucose, was prepared and shown to be a substrate for DesII
      undergoing deamination alone with a specific activity that is only marginally
      reduced (~3-fold) with respect to that of deamination of the natural substrate.
      Furthermore, pH titration of the deamination reaction implicates the presence of
      a hydron acceptor that facilitates catalysis but does not appear to be necessary.
      On the basis of these as well as previously reported results, a mechanism
      involving direct elimination of ammonium with concerted proton transfer to the
      nucleofuge from the adjacent alpha-hydroxyalkyl radical is proposed.

PMID- 29473740
TI  - Electronic Energy Transduction from {Ru(py)4} Chromophores to Cr(III)
      Luminophores.
AB  - Despite the large body of work on {Ru(bpy)2} sensitizer fragments, the same
      attention has not been devoted to their {Ru(py)4} analogues. In this context, we
      explored the donor-acceptor trans-[Ru(L)4{(MU-NC)Cr(CN)5}2]4-, where L =
      pyridine, 4-methoxypyridine, 4-dimethylaminopyridine. We report on the synthesis
      and the crystal structure as well as the electrochemical, spectroscopical, and
      photophysical properties of these trimetallic complexes, including transient
      absorption measurements. We observed emission from chromium-centered d-d states
      upon illuminating into either MLCT or MM'CT absorptions of {Ru(L)4} or {Ru-Cr},
      respectively. The underlying energy transfer is as fast as 600 fs with quantum
      efficiencies ranging from 10% to 100%. These results document that {Ru(py)4}
      sensitizer fragments are as efficient as {Ru(bpy)2} in short-range energy
      transfer scenarios.

PMID- 29473741
TI  - Responses to Comments on "Differential Health Effects of Constant and
      Intermittent Exposure to Formaldehyde in Mice: Implications for Building
      Ventilation Strategies".

PMID- 29473742
TI  - Testing Semiempirical Quantum Mechanical Methods on a Data Set of Interaction
      Energies Mapping Repulsive Contacts in Organic Molecules.
AB  - Semiempirical quantum mechanical (QM) methods with corrections for noncovalent
      interactions provide a favorable combination of accuracy and computational
      efficiency that makes them a useful tool for a study of large molecular systems.
      It was, however, noted that the accuracy of these methods deteriorates at
      intermolecular distances shorter than equilibrium. In this work, we explore this
      issue systematically using a newly developed data set of benchmark interaction
      energies named R160*6. This data set maps repulsive contacts in organic
      molecules, and it consists of 160 model complexes for which six points along the
      dissociation curve are provided. Testing a wide range of semiempirical QM methods
      against the CCSD(T)/CBS benchmark revealed that most methods, and all the
      dispersion-corrected ones, underestimate the repulsion systematically. The worst
      cases are usually hydrogen-hydrogen contacts. The best results were obtained with
      PM6-D3H4 and DFTB3-D3H4, as these methods already contain a correction for the H
      H repulsion, but the errors are still about twice as large as in equilibrium
      geometries.

PMID- 29473743
TI  - Dynamics and Function of Nuclear Bodies during Embryogenesis.
AB  - Nuclear bodies are RNA-rich membraneless organelles in the cell nucleus that
      concentrate specific sets of nuclear proteins and RNA-protein complexes. Nuclear
      bodies such as the nucleolus, Cajal body (CB), and the histone locus body (HLB)
      concentrate factors required for nuclear steps of RNA processing. Formation of
      these nuclear bodies occurs on genomic loci and is frequently associated with
      active sites of transcription. Whether nuclear body formation is dependent on a
      particular gene element, an active process such as transcription, or the nascent
      RNA present at gene loci is a topic of debate. Recently, this question has been
      addressed through studies in model organisms and their embryos. The switch from
      maternally provided RNA and protein to zygotic gene products in early embryos has
      been well characterized in a variety of organisms. This process, termed maternal
      to-zygotic transition, provides an excellent model for studying formation of
      nuclear bodies before, during, and after the transcriptional activation of the
      zygotic genome. Here, we review findings in embryos that reveal key principles in
      the study of the formation and function of nucleoli, CBs, and HLBs. We propose
      that while particular gene elements may contribute to formation of these nuclear
      bodies, active transcription promotes maturation of nuclear bodies and efficient
      RNA processing within them.

PMID- 29473745
TI  - Distinct Carbon Isotope Fractionation Signatures during Biotic and Abiotic
      Reductive Transformation of Chlordecone.
AB  - Chlordecone is a synthetic organochlorine pesticide, extensively used in banana
      plantations of the French West Indies from 1972 to 1993. Due to its environmental
      persistence and bioaccumulation, it has dramatic public health and socio-economic
      impact. Here we describe a method for carbon-directed compound specific isotope
      analysis (CSIA) for chlordecone and apply it to monitor biotic and abiotic
      reductive transformation reactions, selected on the basis of their distinct
      product profiles (polychloroindenes versus lower chlorinated hydrochlordecones).
      Significant carbon isotopic enrichments were observed for all microbially
      mediated transformations (epsilonbulk = -6.80/00 with a Citrobacter strain and
      epsilonbulk = -4.60/00 with a bacterial consortium) and for two abiotic
      transformations (epsilonbulk = -4.10/00 with zerovalent iron and epsilonbulk = 
      2.60/00 with sodium sulfide and vitamin B12). The reaction with titanium(III)
      citrate and vitamin B12, which shows the product profile most similar to that
      observed in biotic transformation, led to low carbon isotope enrichment
      (epsilonbulk =-0.80/00). The CSIA protocol was also applied on representative
      chlordecone formulations previously used in the French West Indies, giving
      similar chlordecone delta13C values from -31.1 +/- 0.20/00 to -34.2 +/- 0.20/00
      for all studied samples. This allows the in situ application of CSIA for the
      assessment of chlordecone persistence.

PMID- 29473744
TI  - Chemo- and Regioselective Lysine Modification on Native Proteins.
AB  - Site-selective chemical conjugation of synthetic molecules to proteins expands
      their functional and therapeutic capacity. Current protein modification methods,
      based on synthetic and biochemical technologies, can achieve site selectivity,
      but these techniques often require extensive sequence engineering or are
      restricted to the N- or C-terminus. Here we show the computer-assisted design of
      sulfonyl acrylate reagents for the modification of a single lysine residue on
      native protein sequences. This feature of the designed sulfonyl acrylates,
      together with the innate and subtle reactivity differences conferred by the
      unique local microenvironment surrounding each lysine, contribute to the observed
      regioselectivity of the reaction. Moreover, this site selectivity was predicted
      computationally, where the lysine with the lowest p Ka was the kinetically
      favored residue at slightly basic pH. Chemoselectivity was also observed as the
      reagent reacted preferentially at lysine, even in those cases when other
      nucleophilic residues such as cysteine were present. The reaction is fast and
      proceeds using a single molar equivalent of the sulfonyl acrylate reagent under
      biocompatible conditions (37  degrees C, pH 8.0). This technology was
      demonstrated by the quantitative and irreversible modification of five different
      proteins including the clinically used therapeutic antibody Trastuzumab without
      prior sequence engineering. Importantly, their native secondary structure and
      functionality is retained after the modification. This regioselective lysine
      modification method allows for further bioconjugation through aza-Michael
      addition to the acrylate electrophile that is generated by spontaneous
      elimination of methanesulfinic acid upon lysine labeling. We showed that a
      protein-antibody conjugate bearing a site-specifically installed fluorophore at
      lysine could be used for selective imaging of apoptotic cells and detection of
      Her2+ cells, respectively. This simple, robust method does not require genetic
      engineering and may be generally used for accessing diverse, well-defined protein
      conjugates for basic biology and therapeutic studies.

PMID- 29473746
TI  - Structures and Protonation States of Hydrophilic-Cationic Diblock Copolymers and
      Their Binding with Plasmid DNA.
AB  - Complexation between plasmid DNA (pDNA) and a set of diblock copolymers, each
      with one cationic block and one hydrophilic, charge-neutral block, is examined. A
      range of hydrophilic block structures are explored, whereas the cationic block is
      fixed as poly( N-(2-aminoethyl) methacrylamide) (PAEMA) with a degree of
      polymerization of 60 +/- 3. The hydrophilic blocks include poly(ethylene glycol)
      (PEG45), poly(oligo(ethylene glycol) methyl ether methacrylate) (P(OEGMA)51), and
      poly(2-deoxy-2-methacrylamido glucopyranose) (PMAG52). The numbers represent the
      degrees of polymerization and are chosen such that the diblock contour lengths
      are similar (37 +/- 2 nm). The three diblock copolymers and a homopolycation
      control, PAEMA59, are compared with respect to their state of dissolution in
      aqueous environments, as well as their complexation with pDNA. The diblock
      copolymers are found to partially aggregate as pH increases above 6, whereas each
      separate block generally dissolves well over a wide pH range. The hydrophilic
      block proves to be a critical parameter in determining the structures of pDNA
      diblock complexes. When the molar ratio of polycation amines to pDNA phosphates
      (i.e., N/P) is less than 1, a bulkier hydrophilic block leads to larger resulting
      complexes. As more polycations are added to the system (N/P > 1.5), colloidal
      stability becomes an important factor, making more water-soluble systems
      stabilize at smaller sizes. Further, the charge density effect on the binding
      thermodynamics is elucidated via calorimetric measurements. P(OEGMA)51- b-PAEMA60
      exhibits a greater amount of endothermic pDNA binding per charged amine at higher
      pH, implying that lower cationic charge density promotes more phosphate pairing
      per amine on average. Also, the colloidal stability and the circular dichroism
      spectral evolution of the pDNA-PAEMA59 complexes are dependent on pH, showing
      noticeable differences between pH = 6.0 vs 7.4. To summarize, controlling the
      solution pH may be crucial in pDNA-polycation complexation, as it impacts
      polycation solubility, binding characteristics, and the final complex properties.
      The findings reported herein should aid researchers in drawing more rigorous
      structure-function correlations in the field of polymeric gene delivery.

PMID- 29473747
TI  - The Crystal Structure and Magnetic Behavior of Quinary Osmate and Ruthenate
      Double Perovskites La ABB'O6 ( A = Ca, Sr; B = Co, Ni; B' = Ru, Os).
AB  - Six La ABB'O6 ( A = Ca, Sr; B = Co, Ni; B' = Ru, Os) double perovskites were
      synthesized, several for the first time, and their crystal structures and
      magnetic behavior were characterized with neutron powder diffraction and direct
      current and alternating-current magnetometry. All six compounds crystallize with
      P21 /n space group symmetry, resulting from a- a- c+ octahedral tilting and
      complete rock salt ordering of transition-metal ions. Despite the electronic
      configurations of the transition-metal ions, either d8-d3 or d7-d3, not one of
      the six compounds shows ferromagnetism as predicted by the Goodenough-Kanamori
      rules. LaSrNiOsO6, LaSrNiRuO6, and LaCaNiRuO6 display long-range
      antiferromagnetic order, while LaCaNiOsO6, LaCaCoOsO6, and LaSrCoOsO6 exhibit
      spin-glass behavior. These compounds are compared to the previously studied
      LaCaCoRuO6 and LaSrCoRuO6, both of which order antiferromagnetically. The
      observed variations in magnetic properties can be attributed largely to the
      response of competing superexchange pathways due to changes in B-O- B' bond
      angles, differences in the radial extent of the 4d ( B' = Ru) and 5d ( B' = Os)
      orbitals, and filling of the t2g orbitals of the 3d ion.

PMID- 29473748
TI  - Comparison of Metal-Ammine Compounds Binding to DNA and Heparin. Glycans as
      Ligands in Bioinorganic Chemistry.
AB  - We present spectroscopic and biophysical approaches to examine the affinity of
      metal-ammine coordination complexes for heparin as a model for heparan sulfate
      (HS). Similar to nucleic acids, the highly anionic nature of heparin means it is
      associated in vivo with physiologically relevant cations, and this work extends
      their bioinorganic chemistry to substitution-inert metal-ammine compounds (M).
      Both indirect and direct assays were developed. M compounds are competitive
      inhibitors of methylene blue (MB)-heparin binding, and the change in the
      absorbance of the dye in the presence or absence of heparin can be used as an
      indirect reporter of M-heparin affinity. A second indirect assay uses the change
      in fluorescence of TAMRA-R9, a nonaarginine linked to a fluorescent TAMRA moiety,
      as a reporter for M-heparin binding. Direct assays are surface plasmon resonance
      (SPR) and isothermal titration calorimetry (ITC). The Kd values for TriplatinNC
      heparin varied to some extent depending on the technique from 33.1 +/- 2 nM (ITC)
      to 66.4 +/- 1.3 nM (MB absorbance assay) and 340 +/- 30 nM (SPR). The differences
      are explained by the nature of the technique and the use of heparin of differing
      molecular weight. Indirect probes using the displacement of ethidium bromide from
      DNA or, separately, fluorescently labeled oligonucleotide (DNA-Fl) can measure
      the relative affinities of heparin and DNA for M compounds. These assays showed
      essentially equivalent affinity of TriplatinNC for heparin and DNA. The
      generality of these methods was confirmed with a series of mononuclear cobalt,
      ruthenium, and platinum compounds with significantly lower affinity because of
      their smaller overall positive charge but in the order [Co(NH3)6]3+ >
      [Ru(NH3)6]3+ > [Pt(NH3)4]2+. The results on heparin can be extrapolated to
      glycosoaminoglycans such as HS, emphasizing the relevance of glycan interactions
      in understanding the biological properties of coordination compounds and the
      utility of the metalloglycomics concept for extending bioinorganic chemistry to
      this class of important biomolecules.

PMID- 29473749
TI  - Virtual Site OPLS Force Field for Imidazolium-Based Ionic Liquids.
AB  - Molecular simulations of ionic liquids can provide deeper insight into the
      relationship between intermolecular interactions and macroscopic measurements for
      the solvents. However, many existing force fields have multiple shortcomings,
      including poor solvent dynamics, the underestimation of hydrogen-bonding
      strength, and errors in solvent interactions/organization. A new force field,
      called optimized potentials for liquid simulation-ionic-liquid virtual site (OPLS
      VSIL), has been developed for imidazolium-based ionic liquids featuring a novel
      topology incorporating a virtual site bisecting the nitrogen atoms that offloads
      negative charge to inside the plane of the ring. Guided by free energy of
      hydration calculations, an empirically derived set of partial charges and
      nonbonded Lennard-Jones terms for both 1-alkyl-3-methylimidazolium and 11
      different anions provided accurate bulk-phase ionic-liquid properties and
      produced radial distribution functions nearly indistinguishable from ab initio
      molecular dynamics simulations. For example, overall mean absolute errors (MAEs)
      of 3.1-3.4% were computed for the density, heat of vaporization, and viscosity of
      approximately 20 different ion pair combinations. Additional physical properties,
      such as, self-diffusion coefficients, heat capacity, and surface tension also
      gave significant MAE improvements using OPLS-VSIL compared to the existing fixed
      charge ionic-liquid force fields. Local interactions, including cation-anion
      hydrogen bonding and pi-pi stacking between the imidazolium rings, were also
      accurately reproduced.

PMID- 29473750
TI  - Excited States of Methylene, Polyenes, and Ozone from Heat-Bath Configuration
      Interaction.
AB  - The electronically excited states of methylene (CH2), ethylene (C2H4), butadiene
      (C4H6), hexatriene (C6H8), and ozone (O3) have long proven challenging due to
      their complex mixtures of static and dynamic correlations. The semistochastic
      heat-bath configuration interaction (SHCI) algorithm, which efficiently and
      systematically approaches the full configuration interaction (FCI) limit, is used
      to provide close approximations to the FCI energies in these systems. This
      article presents the largest FCI-level calculation to date on hexatriene, using a
      polarized double-zeta basis (ANO-L-pVDZ), which gives rise to a Hilbert space
      containing more than 1038 determinants. These calculations give vertical
      excitation energies of 5.58 and 5.59 eV, respectively, for the 21Ag and 11Bu
      states, showing that they are nearly degenerate. The same excitation energies in
      butadiene/ANO-L-pVDZ were found to be 6.58 and 6.45 eV. In addition to these
      benchmarks, our calculations strongly support the presence of a previously
      hypothesized ring-minimum species of ozone that lies 1.3 eV higher than the open
      ring-minimum energy structure and is separated from it by a barrier of 1.11 eV.

PMID- 29473751
TI  - Hexaphenolic Rigid Cages Prepared by Self-Organization of C3 v Tridentates.
AB  - Coordination cages were composed by self-organization of rigid C3 v-symmetric
      heptaarene tridentates and Pd(II) precursors. The heptaarene framework involves
      one mesitylene, three phenol, and three pyridine moieties, which were connected
      by Suzuki coupling reactions. The treatment of the tridentates with
      Pd(dppp)(OTf)2 or Pd(en)(NO3)2 in a 2:3 molar ratio furnished coordination cages,
      which was ascertained by crystallography, 1H NMR and DOSY measurements, and ESI
      TOFMS and UV-vis spectra. The cages have six phenolic hydroxy groups inside and
      were expected to incorporate hydrogen-bonding guest molecules such as
      saccharides. CD and DOSY measurements showed that octyl hexoside guests could be
      incorporated into the cage.

PMID- 29473752
TI  - Reaction Routes for Experimentally Observed Intermediates in the Prebiotic
      Formation of Nucleobases under High-Temperature Conditions.
AB  - The prebiotic synthesis of nucleobases is of particular interest, given the
      experimental evidence that indicated formation of the nucleobases under abiotic
      conditions on the Early Earth under high-temperature conditions. Biomolecules
      have been formed under meteoritic impact scenarios that lead to high temperature
      and the generation of high energy. Free radical pathways for the formation of
      biomolecules are appropriate under these conditions. Density functional theory
      computations were used to study the free radical routes for the formation of
      nucleobases at the UB3LYP/6-311G(d,p) level. We have found that both 5
      aminoimidazole-4-carboxamide (AICA) and 5-(formylamino)imidazole-4-carboxamide
      (fAICA) are formed first from formamide then the nucleobases are formed.
      Calculated results show the radical reaction routes of AICA as a precursor for
      guanine. Both hypoxanthine and xanthine are formed from radical pathways of
      fAICA. In addition, generation of imino-AICA and imino-fAICA has been shown for
      the first time to be needed for the production of adenine, purine, and
      isoguanine. Formation of hypoxanthine and adenine/purine from fAICA and imino
      fAICA, respectively, is consistent with experiments performed nearly seven
      decades ago.

PMID- 29473753
TI  - Macrophage-Membrane-Coated Nanoparticles for Tumor-Targeted Chemotherapy.
AB  - Various delivery vectors have been integrated within biologically derived
      membrane systems to extend their residential time and reduce their
      reticuloendothelial system (RES) clearance during systemic circulation. However,
      rational design is still needed to further improve the in situ penetration
      efficiency of chemo-drug-loaded membrane delivery-system formulations and their
      release profiles at the tumor site. Here, a macrophage-membrane-coated
      nanoparticle is developed for tumor-targeted chemotherapy delivery with a
      controlled release profile in response to tumor microenvironment stimuli. Upon
      fulfilling its mission of tumor homing and RES evasion, the macrophage-membrane
      coating can be shed via morphological changes driven by extracellular
      microenvironment stimuli. The nanoparticles discharged from the outer membrane
      coating show penetration efficiency enhanced by their size advantage and surface
      modifications. After internalization by the tumor cells, the loaded drug is
      quickly released from the nanoparticles in response to the endosome pH. The
      designed macrophage-membrane-coated nanoparticle (cskc-PPiP/PTX@Ma) exhibits an
      enhanced therapeutic effect inherited from both membrane-derived tumor homing and
      step-by-step controlled drug release. Thus, the combination of a biomimetic cell
      membrane and a cascade-responsive polymeric nanoparticle embodies an effective
      drug delivery system tailored to the tumor microenvironment.

PMID- 29473754
TI  - Quantum Interference Assisted Spin Filtering in Graphene Nanoflakes.
AB  - We demonstrate that hexagonal graphene nanoflakes with zigzag edges display
      quantum interference (QI) patterns analogous to benzene molecular junctions. In
      contrast with graphene sheets, these nanoflakes also host magnetism. The
      cooperative effect of QI and magnetism enables spin-dependent quantum
      interference effects that result in a nearly complete spin polarization of the
      current and holds a huge potential for spintronic applications. We understand the
      origin of QI in terms of symmetry arguments, which show the robustness and
      generality of the effect. This also allows us to devise a concrete protocol for
      the electrostatic control of the spin polarization of the current by breaking the
      sublattice symmetry of graphene, by deposition on hexagonal boron nitride, paving
      the way to switchable spin filters. Such a system benefits from all of the
      extraordinary conduction properties of graphene, and at the same time, it does
      not require any external magnetic field to select the spin polarization, as
      magnetism emerges spontaneously at the edges of the nanoflake.

PMID- 29473755
TI  - Quantifying Local Molecular Tension Using Intercalated DNA Fluorescence.
AB  - The ability to measure mechanics and forces in biological nanostructures, such as
      DNA, proteins and cells, is of great importance as a means to analyze
      biomolecular systems. However, current force detection methods often require
      specialized instrumentation. Here, we present a novel and versatile method to
      quantify tension in molecular systems locally and in real time, using
      intercalated DNA fluorescence. This approach can report forces over a range of at
      least ~0.5-65 pN with a resolution of 1-3 pN, using commercially available
      intercalating dyes and a general-purpose fluorescence microscope. We demonstrate
      that the method can be easily implemented to report double-stranded (ds)DNA
      tension in any single-molecule assay that is compatible with fluorescence
      microscopy. This is particularly useful for multiplexed techniques, where
      measuring applied force in parallel is technically challenging. Moreover, tension
      measurements based on local dye binding offer the unique opportunity to determine
      how an applied force is distributed locally within biomolecular structures.
      Exploiting this, we apply our method to quantify the position-dependent force
      profile along the length of flow-stretched DNA and reveal that stretched and
      entwined DNA molecules-mimicking catenated DNA structures in vivo-display
      transient DNA-DNA interactions. The method reported here has obvious and broad
      applications for the study of DNA and DNA-protein interactions. Additionally, we
      propose that it could be employed to measure forces in any system to which dsDNA
      can be tethered, for applications including protein unfolding, chromosome
      mechanics, cell motility, and DNA nanomachines.

PMID- 29473756
TI  - 3D Molecular Representations Based on the Wave Transform for Convolutional Neural
      Networks.
AB  - Convolutional neural networks (CNN) have been successfully used to handle three
      dimensional data and are a natural match for data with spatial structure such as
      3D molecular structures. However, a direct 3D representation of a molecule with
      atoms localized at voxels is too sparse, which leads to poor performance of the
      CNNs. In this work, we present a novel approach where atoms are extended to fill
      other nearby voxels with a transformation based on the wave transform.
      Experimenting on 4.5 million molecules from the Zinc database, we show that our
      proposed representation leads to better performance of CNN-based autoencoders
      than either the voxel-based representation or the previously used Gaussian blur
      of atoms and then successfully apply the new representation to classification
      tasks such as MACCS fingerprint prediction.

PMID- 29473757
TI  - cROSsing the cardiac MIRe: fibroblast-cardiomyocyte ex(o)press.

PMID- 29473758
TI  - Arterial stiffness in women previously with preeclampsia from a semi-rural region
      of South Africa.
AB  - Women with pre-eclampsia have an increased risk of cardiovascular disease later
      in life. The aim of the study was to establish the presence and pattern of
      arterial stiffness in women previously with pre-eclampsia from a semi-rural
      region of South Africa. This was a prospective longitudinal study which involved
      36 previously pre-eclamptic women and 86 non-pregnant controls (NPC) who had a
      past history of non-complicated pregnancy. Maternal wave reflection (augmentation
      index) and carotid-femoral pulse wave velocity were assessed noninvasively, using
      applanation tonometry with the SphygmoCor device. Endothelial function was
      assessed by EndoPAT 2000 device; pneumatic probes were fitted to the index
      fingers; induced flow-mediated reactive hyperemia; the ratio of the readings
      before and after occlusion was then used to calculate the score, the reactive
      hyperemia index (RHI) as a measure of endothelial function. Pulse wave velocity
      remained significantly higher in previously pre-eclamptic women than non-pregnant
      controls up to three months after delivery (p < 0.05), then it reduced to
      nonsignificant values. All blood pressure indices (central and brachial
      pressures), were higher in previously pre-eclamptic women as compared to
      nonpregnant controls up to one year postpartum. Regional (aortic) arterial
      stiffness, though it persists for some time after delivery, is transitory in
      previously pre-eclamptic women from the rural Africa setting. However, their
      increase blood pressure is an indication of compromised arterial compliance in
      women previously with pre-eclampsia.

PMID- 29473759
TI  - Contribution of non-traditional lipid profiles to reduced glomerular filtration
      rate in H-type hypertension population of rural China.
AB  - BACKGROUND: Despite current interest in the unfavourable impact of non
      traditional lipid profiles on cardiovascular disease, information regarding its
      relations to reduced glomerular filtration rate (GFR) in H-type hypertension
      population has not been systemically elucidated. METHODS: Analyses were based
      upon a cross-sectional study of 3259 participants with H-type hypertension who
      underwent assessment of biochemical, anthropometric and blood pressure values.
      Reduced GFR was considered if meeting estimated GFR <60 ml/min/1.73 m2. RESULTS:
      A stepwise multivariate regression analysis indicated that non-traditional lipid
      parameters remained as independent determinants of estimated GFR (all p < .001).
      In multivariable models, we observed a 50%, 51%, 31%, and 24% higher risk for
      decreased GFR with each SD increment in TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios
      and non-HDL-C levels, respectively. The highest quartile of TC/HDL-C, TG/HDL-C
      and LDL-C/HDL-C ratios carried reduced GFR odds (confidence intervals) of 5.50
      (2.50 to 12.09), 6.63 (2.58 to 17.05) and 2.22 (1.15 to 4.29), respectively.
      CONCLUSIONS: The relative independent contribution of non-traditional lipid
      profiles, as indexed by TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C,
      towards reduced GFR putting research evidence at the very heart of lipoprotein
      mediated renal injury set a vital example for applying a clinical and public
      health recommendation for reducing the burden of chronic kidney disease. KEY
      MESSAGES Non-traditional lipid profiles has been linked with the occurrence of
      cardiovascular disease, but none of the studies that address the effect of non
      traditional lipid profiles on reduced GFR risk in H-type hypertension population
      has been specifically established. A greater emphasis of this study resided in
      the intrinsic value of TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C that
      integrate atherogenic and anti-atherogenic lipid molecules to predict the risk of
      reduced GFR among H-type hypertension population and provide insight into the
      pathophysiology of subsequent cardio-cerebrovascular outcomes. In a large Chinese
      H-type hypertension adults, the relative independent contribution of non
      traditional lipid profiles, as indexed by TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios
      and non-HDL-C, towards reduced GFR putting research evidence at the very heart of
      lipoprotein-mediated renal injury set a vital example for applying a clinical and
      public health recommendation for reducing the burden of CKD.

PMID- 29473761
TI  - Correlations between changes in hematological indices of mothers with
      preeclampsia and umbilical cord blood of newborns.
AB  - Preeclampsia is a condition that might severely impact the health of mothers and
      their newborns. The aim of this investigation is to examine hematological
      parameters in mothers with preeclampsia and umbilical cord blood. Eighty
      preecalmptic mothers were recruited in the study. In addition, eighty normal
      pregnant mothers served as controls. Hematological parameters that include
      hemoglobin (Hb), red blood cell count (RBC), red cell distribution width (RDW),
      packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular
      hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood
      cell counts (WBC), platelet counts, mean platelet volume (MPV) and Platelet large
      cell ratio (PLCR) were examined. Results showed a strong association between
      preeclampsia and low birth weight, premature/cesarean delivery and proteinuria (P
      < 0.001). Hb and neutrophils were significantly lower (P < 0.01), whereas RDW,
      PCV, MCV, MCH, MCHC and lymphocytes were significantly higher than normal ones (P
      < 0.01). When cord blood of preeclamptic mothers were compared with that of
      normal ones, similar findings were observed. In addition, results showed
      significant and positive correlations between preeclamptic mothers and their
      newborn in Hb (r2 = 0.075, P < 0.05), PCV (r2 = 0.084, P < 0.01), MCV (r2 =
      0.077, P < 0.05), MCHC (r2 = 0.115, P < 0.01), RBC (r2 = 0.086, P < 0.01) and
      retics (r2 = 0.306, P < 0.01). In conclusion, changes in several hematological
      parameters associated with preeclampsia were correlated in affected mothers and
      their newborns. Such biomarkers can be used to predict pregnancy outcomes in
      women with preeclampsia.

PMID- 29473760
TI  - The acute effect of continuous positive airway pressure titration on blood
      pressure in awake overweight/obese patients with obstructive sleep apnoea.
AB  - OBJECTIVES: Continuous positive airway pressure (CPAP) improves upper airway
      obstruction in patients with obstructive sleep apnoea (OSA), who often are
      overweight-obese. Although it is thought that CPAP improves long-term blood
      pressure control (BP), the impact of acute and short-term CPAP use on the
      cardiovascular system in obese patients has not been described in detail.
      METHODS: Obese patients (body mass index, BMI > 25 kg/m2) with OSA were studied
      awake, supine during incremental CPAP titration (4-20 cmH2O, +2 cmH2O/3 mins). BP
      was measured continuously with a beat-to-beat BP monitor (Ohmeda 2300, Finapres
      Medical Systems, Amsterdam/NL), BP variability (BPV) was calculated as the
      standard deviation of BP at each CPAP level, the 95% confidence interval (95%CI)
      was calculated and changes in BP and BPV were reported. RESULTS: 15 patients (12
      male, 48 +/- 10) years, BMI 38.9 +/- 5.8 kg/m2) were studied; the baseline BP was
      131.0 +/- 10.2/85.1 +/- 9.1 mmHg. BP and BPV increased linearly with CPAP
      titration (systolic BP r = 0.960, p < .001; diastolic BP r = 0.961, p < .001;
      systolic BPV r = 0.662, p = .026; diastolic BPV r = 0.886, p < .001). The
      systolic BP increased by +17% (+23.15 (7.9, 38.4) mmHg; p = .011) and the
      diastolic BP by +23% (+18.27 (2.33, 34.21) mmHg; p = .009), when titrating CPAP
      to 20 cmH2O. Systolic BPV increased by +96% (+5.10 (0.67, 9.53) mmHg; p < .001)
      and was maximal at 14 cmH2O, and diastolic BPV by +97% (+3.02 (0.26, 5.78) mmHg;
      p < .001) at 16 cmH2O. CONCLUSION: Short-term incremental CPAP leads to
      significant increases in BP and BPV in obese patients with OSA while awake.
      Careful titration of pressures is required to minimise the risk of nocturnal
      awakenings while improving BP control.

PMID- 29473762
TI  - Trends in Eye Injuries and Associated Medical Costs among Children in the United
      States, 2002-2014.
AB  - PURPOSE: To describe the trends in eye injuries and associated medical costs
      among children in the United States. METHODS: Data were from the 2002-2014
      Medical Expenditure Panel Survey (MEPS). Eye injuries in children aged <18 years
      were identified by the International Classification of Diseases-9 (ICD-9) codes.
      The trends of cumulative incidence of eye injury, total costs, and average costs
      were estimated from 2002-2014 MEPS data. All costs were adjusted to 2014 US
      dollars. Analyses accounted for the complex stratified multistage survey design
      of the MEPS. We used MarketScan data (2010-2013) to validate outpatient cost
      estimates. RESULTS: The 3-year average cumulative incidence of eye injuries
      declined from 0.56% in 2002-2004 to 0.31% in 2012-2014 (Trend p < 0.001). The
      average annual total costs decreased from $193 million during 2002-2004 to $66
      million during 2012-2014 (p < 0.001). CONCLUSION: The MEPS data showed that among
      children aged <18 years, the incidence of eye injuries and associated financial
      burden substantially declined during 2002-2014, highlighting the progress in
      preventing children eye injuries. Continuing efforts are needed to further reduce
      the burden in this population.

PMID- 29473763
TI  - Statin-induced myalgia and myositis: an update on pathogenesis and clinical
      recommendations.
AB  - INTRODUCTION: Musculoskeletal manifestations are well-recognized side effects of
      treatment with statins. New advances in this field have appeared in recent years.
      This review focuses on the diagnosis of these conditions and their underlying
      pathogenesis, in particular immune-mediated necrotizing myopathy. Areas covered:
      Clinical phenotypes including rhabdomyolysis, myalgia and/or mild hyperCKemia,
      self-limited toxin statin myopathy, and immune-mediated necrotizing myopathy are
      herein described. Therapeutic recommendations and a diagnostic algorithm in
      statin-associated myopathy are also proposed. The etiology and pathogenesis of
      statin-induced myopathy has mainly focused on the anti-HMGCR antibodies and the
      responsibility of the immune-mediated necrotizing myopathy is discussed. The fact
      that patients who have not been exposed to statins may develop statin-associated
      autoimmune myopathy with anti-HMGCR antibodies is also addressed. The literature
      search strategy included terms identified by searches of PubMed between 1969 and
      December 2017. The search terms 'myositis', 'statin-induced autoimmune myopathy',
      'immune-mediate necrotizing myopathy', 'statins', 'muscular manifestations', and
      'anti-HMGCR antibodies' were used. Expert commentary: Full characterization of
      the known phenotypes of statin toxicity and the specific role of the anti-HMGCR
      in those exposed and not exposed (i.e. juvenile forms) to statins and in some
      types of neoplasms is of paramount relevance.

PMID- 29473764
TI  - Effects of gestational diabetes mellitus on time to delivery and pregnancy
      outcomes in full-term pregnancies with dinoprostone labor induction.
AB  - OBJECTIVE: To investigate the effects of gestational diabetes mellitus (GDM) on
      time to delivery and perinatal outcomes in full-term pregnancies underwent
      dinoprostone-induced labor. METHODS: GDM patients that underwent labor induction
      with dinoprostone vaginal inserts were retrospectively recruited. Full-term
      pregnancies with normal glucose tolerance (NGT) that underwent labor induction at
      the same period were recruited as control. Time to delivery and perinatal
      outcomes were compared between the two groups. RESULTS: A total of 1555
      pregnancies with 226 GDM and 1329 NGT were recruited. GDM pregnancies had older
      ages, lower gestational age, higher body mass index (BMI) and abortion history,
      and more multigravida than NGT pregnancies (P< 0.05). Univariate analysis showed
      no significant difference in time to delivery and delivery rates between the two
      groups. However, after adjusted in a multivariate analysis model, the delivery
      rates of GDM women delivered within 12, 24, 36 or 48 h and those vaginally
      delivered within 12 or 36 h were significantly lower than those in the NGT group
      (P< 0.05). Perinatal outcomes were clinically similar between the two groups.
      CONCLUSION: GDM did not affect the time to delivery, cesarean delivery and other
      perinatal outcomes in Chinese women underwent dinoprostone-induced labor.
      However, it may be associated with the lower rates of delivery within different
      time intervals.

PMID- 29473765
TI  - Antimicrobial molecules in the lung: formulation challenges and future directions
      for innovation.
AB  - Inhaled antimicrobials have been extremely beneficial in treating respiratory
      infections, particularly chronic infections in a lung with cystic fibrosis. The
      pulmonary delivery of antibiotics has been demonstrated to improve treatment
      efficacy, reduce systemic side effects and, critically, reduce drug exposure to
      commensal bacteria compared with systemic administration, reducing selective
      pressure for antimicrobial resistance. This review will explore the specific
      challenges of pulmonary delivery of a number of differing antimicrobial
      molecules, and the formulation and technological approaches that have been used
      to overcome these difficulties. It will also explore the future challenges being
      faced in the development of inhaled products and respiratory infection treatment,
      and identify future directions of innovation, with a particular focus on
      respiratory infections caused by multiple drug-resistant pathogens.

PMID- 29473766
TI  - Childcare Environment and Japanese Children Who Are Overweight in Early
      Childhood.
AB  - BACKGROUND: Maternal employment may affect child care styles and contribute to
      the increasing prevalence of overweight children. We explored the potential risk
      factors for becoming overweight during early childhood, especially in the child
      care environment. METHODS: We conducted a retrospective cohort study using data
      from health check-up services from 2007 to 2015 in Kobe, Japan. The main outcome
      was being overweight at age 3 years, which was defined by the International
      Obesity Task Force cutoffs. Environmental, maternal, and infantile factors were
      examined as possible risk factors for childhood overweight. RESULTS: Of 31,463
      infants, 1315 (4.2%) were classified as overweight at age 3 years. Compared with
      children who were cared for by their mothers during the day at 4 and 18 months,
      the adjusted odds ratio (aOR) for becoming overweight for those who were not
      cared for by their mothers was 1.52: 95% confidence interval (CI), 1.16-1.99.
      Long sleep duration was associated with lower risk of childhood overweight: aOR,
      0.79; 95% CI, 0.66-0.96. CONCLUSION: Less daytime care by mothers and shorter
      sleep duration were associated with increased risk of becoming overweight during
      childhood. Further studies are needed to determine on how the effect of those
      factors may be diminished with respect to childhood overweight.

PMID- 29473767
TI  - Computational modeling of blast induced whole-body injury: a review.
AB  - Blast injuries affect millions of lives across the globe due to its traumatic
      after effects on the brain and the whole body. To date, military grade armour
      materials are designed to mitigate ballistic and shrapnel attacks but are less
      effective in resisting blast impacts. In order to improve blast absorption
      characteristics of armours, the first key step is thoroughly understands the
      effects of blasts on the human body itself. In the last decade, a plethora of
      experimental and computational work has been carried out to investigate the
      mechanics and pathophysiology of Traumatic Brain Injury (TBI). However, very few
      attempts have been made so far to study the effect of blasts on the various other
      parts of the body such as the sensory organs (eyes and ears), nervous system,
      thorax, extremities, internal organs (such as the lungs) and the skeletal system.
      While an experimental evaluation of blast effects on such physiological systems
      is difficult, developing finite element (FE) models could allow the recreation of
      realistic blast scenarios on full scale human models and simulate the effects.
      The current article reviews the state-of-the-art in computational research in
      blast induced whole-body injury modelling, which would not only help in
      identifying the areas in which further research is required, but would also be
      indispensable for understanding body location specific armour design criteria for
      improved blast injury mitigation.

PMID- 29473768
TI  - Comparison of definitive-intent finely fractionated and palliative-intent
      coarsely fractionated radiotherapy as adjuvant treatment of feline microscopic
      injection-site sarcoma.
AB  - Objectives The aim of this retrospective, bi-institutional study was to evaluate
      the progression-free interval in a cohort of cats with postoperative microscopic
      injection-site sarcoma (ISS) treated with two different radiotherapy protocols.
      Methods Included in the study were cats with ISSs undergoing macroscopic surgical
      removal and subsequent electron beam radiotherapy treatment with either a finely
      fractionated protocol (48 or 52.8 Gy over 4 weeks delivered in 12 or 16
      fractions) or a coarsely fractionated protocol (36 Gy over 3 weeks administered
      in six fractions). Medical records were reviewed and follow-up information was
      collected. The Kaplan-Meier method and log-rank test were used to compare the
      progression-free interval (PFI) between the two protocols and to test the
      influence of many clinical variables. Results Fifty-nine cats were included; 38
      underwent a finely fractionated protocol and 21 a coarsely fractionated protocol.
      PFI was not significantly different between the two groups. Overall PFI was 2000
      days (2000 vs 540 days; P = 0.449). When only first-occurrence cases were
      included, median PFI was significantly longer in the finely fractionated group
      compared with the coarsely fractionated group (1430 vs 540 days; P = 0.007). In
      cats that underwent multiple surgeries PFI was not different between protocols
      (233 vs 395 days; P = 0.353). Conclusions and relevance Cats with primarily
      occurring ISSs appear to benefit from postoperative finely fractionated
      radiotherapy. The same benefit was not evident in cats that underwent multiple
      surgeries and we think a coarsely fractionated protocol would be indicated in
      these cases.

PMID- 29473769
TI  - Identification and human exposure prediction of two aldehyde oxidase-mediated
      metabolites of a methylquinoline-containing drug candidate.
AB  - 1. Aldehyde oxidase (AO enzymes)-mediated oxidation predominantly occurs at a
      carbon atom adjacent to the nitrogen on aromatic azaheterocycles. In the current
      report, we identified that AO enzymes oxidation took place at both the C-2 and C
      4 positions of the methylquinoline moiety of Compound A based on data from mass
      spectrometric analysis, AO enzymes "litmus" test, and comparison with authentic
      standards. 2. To assess the potential for inadequate coverage for these two AO
      enzyme-mediated metabolites in nonclinical safety studies, given concerns due to
      differences in AO enzymes expression between preclinical species and humans, the
      human circulating levels of the two AO enzyme-mediated metabolites were predicted
      prospectively using in vitro and in vivo models. Both formation clearance and
      elimination clearance of the two metabolites were predicted based on in vitro to
      in vivo correlation and comparison with in vivo data from rats. 3. The result
      showed that the 4-OH metabolite of Compound A would account for less than 3% of
      the total drug-related exposure in human plasma, while the exposure to the 2-oxo
      metabolite would be relatively high (~70%). 4. The predicted human exposure
      levels for the two metabolites are in similar ranges as those observed in
      monkeys. These data taken together support the advancement to clinical
      development of Compound A.

PMID- 29473770
TI  - Exploring Factors Contributing to Medication Errors with Opioids in Australian
      Specialist Palliative Care Inpatient Services: A Multi-Incident Analysis.
AB  - BACKGROUND: Opioid errors have the potential to cause significant patient harm.
      These high-risk medications are used in high volumes in palliative care services
      to manage pain and other symptoms. Palliative patients are at greater risk of
      harm from opioid errors, as they are generally older and taking numerous
      medications to manage multiple comorbidities. Understanding factors contributing
      to opioid errors in inpatient palliative care services is a largely
      underexplored, yet, essential aspect of patient safety. OBJECTIVE: To explore and
      identify the characteristics and associated contributing factors of reported
      opioid errors in palliative care inpatient services using a multi-incident
      analysis framework. DESIGN: A multi-incident analysis of opioid errors reported
      over three years in two Australian specialist palliative care inpatient services.
      RESULTS: A total of 78 opioid errors were reported. The majority (76%) of these
      errors occurred during opioid administration, primarily due to omitted dose (34%)
      and wrong dose (17%) errors. Eighty-five percent of reported errors reached the
      patient resulting in opioid underdose for over half (59%) of these patients. Over
      one-third (37%) of errors caused patient harm, which required clinical
      intervention. Error contributing factors included the following: noncompliance
      with policy; individual factors such as distraction; poor clinical communication
      systems; and workload. CONCLUSIONS: This multi-incident analysis has provided
      initial insights into factors contributing to opioid errors in palliative care
      inpatient services. Further exploration is warranted to understand palliative
      care clinicians' perspectives of systems, individual, and patient factors that
      influence safe opioid delivery processes.

PMID- 29473771
TI  - Illicit drug use and traumatic dental injuries in adolescents.
AB  - OBJECTIVE: To explore the association between illicit drug use and traumatic
      dental injuries (TDI) among adolescents. METHOD: We used data from 618
      adolescents who participated in Phases I and III of Research with East
      Adolescents Community Health Survey (RELACHS), a longitudinal school-based study
      of adolescents in East London. Illicit drug use was collected when participants
      were 11-12 and 15-16 years old (Phases I and III, respectively). Clinical
      examinations for TDI were conducted in Phase III only. The association of
      lifetime prevalence of illicit drug use at ages 11-12 and 15-16 years with TDI
      was evaluated in crude and adjusted binary logistic regression models. RESULTS:
      Overall, 6.3% and 25.4% of adolescents reported having ever used illicit drugs at
      ages 11-12 (Phase I) and 15-16 years (Phase III), respectively. Also, 8.7% of
      adolescents were found to have TDI at age 15-16 years. There was no significant
      association between lifetime prevalence of illicit drug use reported at age 11-12
      years (Odds Ratio: 1.07; 95% Confidence Interval: 0.45-2.54) or age 15-16 years
      (OR: 1.19; 95%CI: 0.74-1.93) and TDI. CONCLUSION: This study found no support for
      an association between illicit drug use and TDI among adolescents from East
      London.

PMID- 29473772
TI  - Letter to the Editor. Multiple meningiomas.

PMID- 29473773
TI  - MLN8237 treatment in an orthoxenograft murine model for malignant peripheral
      nerve sheath tumors.
AB  - OBJECTIVE Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue
      sarcomas arising from peripheral nerves. MPNSTs have increased expression of the
      oncogene aurora kinase A, leading to enhanced cellular proliferation. This makes
      them extremely aggressive with high potential for metastasis and a devastating
      prognosis; 5-year survival estimates range from a dismal 15% to 60%. MPNSTs are
      currently treated with resection (sometimes requiring limb amputation) in
      combination with chemoradiation, both of which demonstrate limited effectiveness.
      The authors present the results of immunohistochemical, in vitro, and in vivo
      analyses of MLN8237 for the treatment of MPNSTs in an orthoxenograft murine
      model. METHODS Immunohistochemistry was performed on tumor sections to confirm
      the increased expression of aurora kinase A. Cytotoxicity analysis was then
      performed on an MPNST cell line (STS26T) to assess the efficacy of MLN8237 in
      vitro. A murine orthoxenograft MPNST model transfected to express luciferase was
      then developed to assess the efficacy of aurora kinase A inhibition in the
      treatment of MPNSTs in vivo. Mice with confirmed tumor on in vivo imaging were
      divided into 3 groups: 1) controls, 2) mice treated with MLN8237, and 3) mice
      treated with doxorubicin/ifosfamide. Treatment was carried out for 32 days, with
      imaging performed at weekly intervals until postinjection day 42. Average
      bioluminescence among groups was compared at weekly intervals using 1-way ANOVA.
      A survival analysis was performed using Kaplan-Meier curves. RESULTS
      Immunohistochemical analysis showed robust expression of aurora kinase A in tumor
      cells. Cytotoxicity analysis revealed STS26T susceptibility to MLN8237 in vitro.
      The group receiving treatment with MLN8237 showed a statistically significant
      difference in tumor size compared with the control group starting at
      postinjection day 21 and persisting until the end of the study. The MLN8237 group
      also showed decreased tumor size compared with the doxorubicin/ifosfamide group
      at the conclusion of the study (p = 0.036). Survival analysis revealed a
      significantly increased median survival in the MLN8237 group (83 days) compared
      with both the control (64 days) and doxorubicin/ifosfamide (67 days) groups. A
      hazard ratio comparing the 2 treatment groups showed a decreased hazard rate in
      the MLN8237 group compared with the doxorubicin/ifosfamide group (HR 2.945; p =
      0.0134). CONCLUSIONS The results of this study demonstrate that MLN8237 is
      superior to combination treatment with doxorubicin/ifosfamide in a preclinical
      orthoxenograft murine model. These data have major implications for the future of
      MPNST research by providing a robust murine model as well as providing evidence
      that MLN8237 may be an effective treatment for MPNSTs.

PMID- 29473774
TI  - The Annual Neurosurgery Charity Softball Tournament: 15th Anniversary
      Commemorative Article. The creation, development, and establishment of a
      neurosurgical tradition.

PMID- 29473775
TI  - Stereotactic radiosurgery for tremor: systematic review.
AB  - OBJECTIVE The aim of this systematic review is to offer an objective summary of
      the published literature relating to stereotactic radiosurgery (SRS) for tremor
      and consensus guideline recommendations. METHODS This systematic review was
      performed up to December 2016. Article selection was performed by searching the
      MEDLINE (PubMed) and EMBASE electronic bibliographic databases. The following key
      words were used: "radiosurgery" and "tremor" or "Parkinson's disease" or
      "multiple sclerosis" or "essential tremor" or "thalamotomy" or "pallidotomy." The
      search strategy was not limited by study design but only included key words in
      the English language, so at least the abstract had to be in English. RESULTS A
      total of 34 full-text articles were included in the analysis. Three studies were
      prospective studies, 1 was a retrospective comparative study, and the remaining
      30 were retrospective studies. The one retrospective comparative study evaluating
      deep brain stimulation (DBS), radiofrequency thermocoagulation (RFT), and SRS
      reported similar tremor control rates, more permanent complications after DBS and
      RFT, more recurrence after RFT, and a longer latency period to clinical response
      with SRS. Similar tremor reduction rates in most of the reports were observed
      with SRS thalamotomy (mean 88%). Clinical complications were rare and usually not
      permanent (range 0%-100%, mean 17%, median 2%). Follow-up in general was too
      short to confirm long-term results. CONCLUSIONS SRS to the unilateral thalamic
      ventral intermediate nucleus, with a dose of 130-150 Gy, is a well-tolerated and
      effective treatment for reducing medically refractory tremor, and one that is
      recommended by the International Stereotactic Radiosurgery Society.

PMID- 29473776
TI  - Letter to the Editor. Endoscopic transpterygoid corridor.

PMID- 29473777
TI  - Quantitative and qualitative analysis of bone flap resorption in patients
      undergoing cranioplasty after decompressive craniectomy.
AB  - OBJECTIVE Autologous bone cranioplasty after decompressive craniectomy entails a
      notable burden of difficult postoperative complications, such as infection and
      bone flap resorption (BFR), leading to mechanical failure. The prevalence and
      significance of asymptomatic BFR is currently unclear. The aim of this study was
      to radiologically monitor the long-term bone flap survival and bone quality
      change in patients undergoing autologous cranioplasty. METHODS The authors
      identified all 45 patients who underwent autologous cranioplasty at Oulu
      University Hospital, Finland, between January 2004 and December 2014. Using
      perioperative and follow-up CT scans, the volumes and radiodensities of the
      intact bone flap prior to surgery and at follow-up were calculated. Relative
      changes in bone flap volume and radiodensity were then determined to assess
      cranioplasty survival. Sufficient CT scans were obtainable from 41 (91.1%) of the
      45 patients. RESULTS The 41 patients were followed up for a median duration of
      3.79 years (25th and 75th percentiles = 1.55 and 6.66). Thirty-seven (90.2%) of
      the 41 patients had some degree of BFR and 13 (31.7%) had a remaining bone flap
      volume of less than 80%. Patients younger than 30 years of age had a mean
      decrease of 15.8% in bone flap volume compared with the rest of the cohort. Bone
      flap volume was not found to decrease linearly with the passing of time, however.
      The effects of lifestyle factors and comorbidities on BFR were nonsignificant.
      CONCLUSIONS In this study BFR was a very common phenomenon, occurring at least to
      some degree in 90% of the patients. Decreases in bone volume were especially
      prominent in patients younger than 30 years of age. Because the progression of
      resorption during follow-up was nonlinear, routine follow-up CT scans appear
      unnecessary in monitoring the progression of BFR; instead, clinical follow-up
      with mechanical stability assessment is advised. Partial resorption is most
      likely a normal physiological phenomenon during the bone revitalization process.

PMID- 29473778
TI  - Assessment of the praxis circuit in glioma surgery to reduce the incidence of
      postoperative and long-term apraxia: a new intraoperative test.
AB  - OBJECTIVE Apraxia is a cognitive-motor deficit affecting the execution of skilled
      movements, termed praxis gestures, in the absence of primary sensory or motor
      disorders. In patients affected by stroke, apraxia is associated with lesions of
      the lateral parietofrontal stream, connecting the posterior parietal areas with
      the ventrolateral premotor area and subserving sensory-motor integration for the
      hand movements. In the neurosurgical literature to date, there are few reports
      regarding the incidence of apraxia after glioma surgery. A retrospective analysis
      of patients who harbored a glioma around the central sulcus and close to the
      parietofrontal circuits in depth showed a high incidence of long-term
      postoperative hand apraxia, impairing the patients' quality of life. To avoid the
      occurrence of postoperative apraxia, the authors sought to develop an innovative
      intraoperative hand manipulation task (HMt) that can be used in association with
      the brain mapping technique to identify and preserve the cortical and subcortical
      structures belonging to the praxis network. METHODS The intraoperative efficacy
      of the HMt was investigated by comparing the incidence of postoperative ideomotor
      apraxia between patients undergoing mapping with (n = 79) and without (n = 41)
      the HMt. Patient groups were balanced for all demographic and clinical features.
      RESULTS In patients with lesions in the dominant hemisphere, the HMt dramatically
      reduced the incidence of apraxia, with a higher sensitivity for the ideomotor
      than for the constructional abilities; patients with lesions in the nondominant
      hemisphere benefitted from the HMt for both ideomotor and constructional
      abilities. The administration of the test did not reduce the extent of resection.
      CONCLUSIONS The HMt is a safe and feasible intraoperative tool that allowed
      surgeons to prevent the occurrence of long-term hand apraxia while attaining
      resection goals for the surgical treatment of glioma.

PMID- 29473779
TI  - Impact of timing of ventriculoperitoneal shunt placement on outcome in
      posttraumatic hydrocephalus.
AB  - OBJECTIVE Posttraumatic hydrocephalus (PTH) is a frequent sequela of traumatic
      brain injury (TBI) and complication of related cranial surgery. The roles of PTH
      and the timing of cerebrospinal fluid (CSF) shunt placement in TBI outcome have
      not been well described. The goal of this study was to assess the impact of
      hydrocephalus and timing of ventriculoperitoneal (VP) shunt placement on outcome
      during inpatient rehabilitation after TBI. METHODS In this cohort study, all TBI
      patients admitted to Craig Hospital between 2009 and 2013 were evaluated for PTH,
      defined as ventriculomegaly, and hydrocephalus symptoms, delayed or deteriorating
      recovery, or elevated opening pressure on lumbar puncture. Extent of
      ventriculomegaly was quantified by the Evans index from CT scans. Outcome
      measures were emergence from and duration of posttraumatic amnesia (PTA) and
      functional status as assessed by means of the Functional Independence Measure
      (FIM). Findings in this group were compared to findings in a group of TBI
      patients without PTH (controls) who were admitted for inpatient rehabilitation
      during the same study period and met specific criteria for inclusion. RESULTS A
      total of 701 patients were admitted with TBI during the study period. Of these
      patients, 59 (8%) were diagnosed with PTH and were included in this study as the
      PTH group, and 204 who were admitted for rehabilitation and met the criteria for
      inclusion as controls constituted the comparison group (no-PTH group). PTH was
      associated with initial postinjury failure to follow commands, midline shift or
      cistern compression, subcortical contusion, and craniotomy or craniectomy. In
      multivariable analyses, independent predictors of longer PTA duration and lower
      FIM score at rehabilitation discharge were PTH, emergency department Glasgow Coma
      Scale motor score < 6, and longer time from injury to rehabilitation admission.
      PTH accounted for a 51-day increase in PTA duration and a 29-point reduction in
      discharge FIM score. In 40% of PTH patients with preshunt CT brain imaging
      analyzed, ventriculomegaly (Evans index > 0.3) was observed 3 or more days before
      VP shunt placement (median 10 days, range 3-102 days). Among PTH patients who
      received a VP shunt, earlier placement was associated with better outcome by all
      measures assessed and independently predicted better FIM total score and shorter
      PTA duration. CONCLUSIONS Posttraumatic hydrocephalus predicts worse outcome
      during inpatient rehabilitation, with poorer functional outcomes and longer
      duration of PTA. In shunt-treated PTH patients, earlier CSF shunting predicted
      improved recovery. These results suggest that clinical vigilance for PTH onset
      and additional studies on timing of CSF diversion are warranted.

PMID- 29473780
TI  - Letter to the Editor. Microsurgical anatomy in the reappearance of AVMs after
      complete resection.

PMID- 29473781
TI  - Prediction of depression and anxiety via patient-assessed tremor severity, not
      physician-reported motor symptom severity, in patients with Parkinson's disease
      or essential tremor who have undergone deep brain stimulation.
AB  - OBJECTIVE Deep brain stimulation (DBS) is an effective therapy for movement
      disorders such as idiopathic Parkinson's disease (PD) and essential tremor (ET).
      However, some patients who demonstrate benefit on objective motor function tests
      do not experience postoperative improvement in depression or anxiety, 2 important
      components of quality of life (QOL). Thus, to examine other possible explanations
      for the lack of a post-DBS correlation between improved objective motor function
      and decreased depression or anxiety, the authors investigated whether patient
      perceptions of motor symptom severity might contribute to disease-associated
      depression and anxiety. METHODS The authors performed a retrospective chart
      review of PD and ET patients who had undergone DBS at the Cleveland Clinic in the
      period from 2009 to 2013. Patient demographics, diagnosis (PD, ET), motor symptom
      severity, and QOL measures (Primary Care Evaluation of Mental Disorders 9-item
      Patient Health Questionnaire [PHQ-9] for depression, Generalized Anxiety Disorder
      7-item Scale [GAD-7], and patient-assessed tremor scores) were collected at 4
      time points: preoperatively, postoperatively, 1-year follow-up, and 2-year follow
      up. Multivariable prediction models with solutions for fixed effects were
      constructed to assess the correlation of predictor variables with PHQ-9 and GAD-7
      scores. Predictor variables included age, sex, visit time, diagnosis (PD vs ET),
      patient-assessed tremor, physician-reported tremor, Unified Parkinson's Disease
      Rating Scale part III (UPDRS-III) score, and patient-assessed tremor over time.
      RESULTS Seventy PD patients and 17 ET patients were included in this analysis.
      Mean postoperative and 1-year follow-up UPDRS-III and physician-reported tremor
      scores were significantly decreased compared with preoperative scores (p <
      0.0001). Two-year follow-up physician-reported tremor was also significantly
      decreased from preoperative scores (p < 0.0001). Only a diagnosis of PD (p =
      0.0047) and the patient-assessed tremor rating (p < 0.0001) were significantly
      predictive of depression. A greater time since surgery, in general, significantly
      decreased anxiety scores (p < 0.0001) except when a worsening of patient-assessed
      tremor was reported over the same time period (p < 0.0013). CONCLUSIONS Patient
      assessed tremor severity alone was predictive of depression in PD and ET
      following DBS. This finding suggests that a patient's perception of illness plays
      a greater role in depression than objective physical disability regardless of the
      time since surgical intervention. In addition, while anxiety may be attenuated by
      DBS, patient-assessed return of tremor over time can increase anxiety,
      highlighting the importance of long-term follow-up for behavioral health features
      in chronic neurological disorders. Together, these data suggest that the patient
      experience of motor symptoms plays a role in depression and anxiety-a finding
      that warrants consideration when evaluating, treating, and following movement
      disorder patients who are candidates for DBS.

PMID- 29473782
TI  - Letter to the Editor. Pullout complications with external ventricular drains.

PMID- 29473783
TI  - Anterior clinoidectomy using an extradural and intradural 2-step hybrid
      technique.
AB  - Anterior clinoidectomy is a difficult yet essential technique in skull base
      surgery. Two main techniques (extradural and intradural) with multiple
      modifications have been proposed to increase efficiency and avoid complications.
      In this study, the authors sought to develop a hybrid technique based on
      localization of the optic strut (OS) to combine the advantages and avoid the
      disadvantages of both techniques. Ten cadaveric specimens were prepared for
      surgical simulation. After a standard pterional craniotomy, the anterior clinoid
      process (ACP) was resected in 2 steps. The segment anterior to the OS was
      resected extradurally, while the segment posterior to the OS was resected
      intradurally. The proposed technique was performed in 6 clinical cases to
      evaluate its safety and efficiency. Anterior clinoidectomy was successfully
      performed in all cadaveric specimens and all 6 patients by using the proposed
      technique. The extradural phase enabled early decompression of the optic nerve
      while avoiding the adjacent internal carotid artery. The OS was drilled
      intradurally under direct visualization of the adjacent neurovascular structures.
      The described landmarks were easily identifiable and applicable in the surgically
      treated patients. No operative complication was encountered. A proposed 2-step
      hybrid technique combines the advantages of the extradural and intradural
      techniques while avoiding their disadvantages. This technique allows reduced
      intradural drilling and subarachnoid bone dust deposition. Moreover, the most
      critical part of the clinoidectomy-that is, drilling of the OS and removal of the
      body of the ACP-is left for the intradural phase, when critical neurovascular
      structures can be directly viewed.

PMID- 29473784
TI  - Strigolactones are common regulators in induction of stomatal closure in planta.
AB  - Strigolactones (SLs) have been implicated in many plant biological processes,
      including growth and development and the acclimation to environmental stress. We
      recently reported that SLs intrinsically acted as prominent regulators in
      induction of stomatal closure. Here we present evidence that the effect of SLs on
      stotamal closure is not limited to Arabidopsis, and thus SLs could serve as
      common regulators in the modulation of stomatal apertures of various plant
      species. Nevertheless, TIS108, a SL-biosynthetic inhibitor, exerted no effect on
      stomatal apertures. In addition, the SL receptor mutant atd14-5, similar to SL
      deficient and more axillary growth 2 (max2) mutants, exhibited hypersensitivity
      to drought stress. Altogether, these results reinforce the role of SLs as common
      regulators in stress resilience.

PMID- 29473785
TI  - Muscle morphology of the vastus lateralis is strongly related to ergometer
      performance, sprint capacity and endurance capacity in Olympic rowers.
AB  - Rowers need to combine high sprint and endurance capacities. Muscle morphology
      largely explains muscle power generating capacity, however, little is known on
      how muscle morphology relates to rowing performance measures. The aim was to
      determine how muscle morphology of the vastus lateralis relates to rowing
      ergometer performance, sprint and endurance capacity of Olympic rowers. Eighteen
      rowers (12?, 6?, who competed at 2016 Olympics) performed an incremental rowing
      test to obtain maximal oxygen consumption, reflecting endurance capacity. Sprint
      capacity was assessed by Wingate cycling peak power. M. vastus lateralis
      morphology (volume, physiological cross-sectional area, fascicle length and
      pennation angle) was derived from 3-dimensional ultrasound imaging. Thirteen
      rowers (7?, 6?) completed a 2000-m rowing ergometer time trial. Muscle volume
      largely explained variance in 2000-m rowing performance (R2 = 0.85), maximal
      oxygen consumption (R2 = 0.65), and Wingate peak power (R2 = 0.82). When
      normalized for differences in body size, maximal oxygen consumption and Wingate
      peak power were negatively related in males (r = -0.94). Fascicle length, not
      physiological cross-sectional area, attributed to normalized peak power. In
      conclusion, vastus lateralis volume largely explains variance in rowing ergometer
      performance, sprint and endurance capacity. For a high normalized sprint
      capacity, athletes may benefit from long fascicles rather than a large
      physiological cross-sectional area.

PMID- 29473786
TI  - Online measurement of phthalate-particulate matter interactions by membrane
      introduction mass spectrometry (MIMS).
AB  - To enable further study and assessment of indoor inhalation exposure risk, an
      online apparatus enabling measurement of semi-volatile compound partitioning on
      household particulates was developed. An example for use of the apparatus is
      described using dimethyl phthalate (DMP). The system employs direct measurement
      by membrane introduction mass spectrometry (MIMS). The MIMS system was calibrated
      using known gas phase DMP concentrations produced by gravimetrically calibrated
      permeation devices. The quantity of DMP sorbed by particles is described first
      using a model particle type, a reverse-phase liquid chromatography packing
      material, and then with a household dust sample. In addition, the desorption of
      semi-volatile compounds from a household dust sample was monitored using the
      apparatus, and characteristic fragment ion signals for phthalate compounds were
      observed.

PMID- 29473787
TI  - Identification of targeting peptides for the diagnosis of myocarditis.
AB  - AIM: Current diagnostic tests for myocarditis are invasive and have low
      diagnostic value. Our aim was to identify potential targeting peptides to detect
      early myocarditis following intravenous delivery. MATERIALS & METHODS: We used an
      animal model of experimental autoimmune myocarditis and a phage display library
      to identify potential targeting peptides. After several steps, we selected two
      peptides, MyH-PhD-05 and MyH-PhD-120, for in vivo screening using fluorescent
      imaging. Immunofluorescence and proteonomic analysis was used to identify
      potential cellular and molecular targets of MyH-PhD-05. Echocardiography was used
      to assess functional changes. RESULTS: Peptide MyH-PhD-05 was able to detect
      animals with severe myocarditis even in the absence of functional changes.
      Immunofluorescence demonstrated that MyH-PhD-05 colocalizes with CD4+ T cells and
      monocytes (CD11b+) in cardiac infiltrates. CONCLUSION: We identified potential
      targeting peptides for the diagnosis of myocarditis. Future studies will focus on
      better identification of potential targets and translating this technology to
      clinically relevant imaging modalities.

PMID- 29473788
TI  - Methylglyoxal induced advanced glycation end products (AGE)/receptor for AGE
      (RAGE)-mediated angiogenic impairment in bone marrow-derived endothelial
      progenitor cells.
AB  - Endothelial cells (ECs) maintain the structure and function of blood vessels and
      are readily exposed to exogenous and endogenous toxic substances in the
      circulatory system. Bone marrow-derived endothelial progenitor cells (EPCs)
      circulate in the blood and differentiate to EC, which are known to participate in
      angiogenesis and regeneration of injured vessels. Dysfunction in EPC contributes
      to cardiovascular complications in patients with diabetes, but the precise
      molecular mechanisms underlying diabetic EPC abnormalities are not completely
      understood. The aim of this study was to investigate the mechanisms underlying
      diabetic EPC dysfunction using methylglyoxal (MG), an endogenous toxic diabetic
      metabolite. Data demonstrated that MG decreased cell viability and protein
      expression of vascular endothelial growth factor receptor (VEGFR)-2 associated
      with functional impairment of tube formation in EPC. The generation of advanced
      glycation end (AGE) products was increased in EPC following exposure to MG.
      Blockage of receptor for AGE (RAGE) by FPS-ZM1, a specific antagonist for RAGE,
      significantly reversed the decrease of VEGFR-2 protein expression and angiogenic
      dysfunction in MG-incubated EPC. Taken together, data demonstrated that MG
      induced angiogenic impairment in EPC via alterations in the AGE/RAGE-VEGFR-2
      pathway which may be utilized in the development of potential therapeutic and
      preventive targets for diabetic vascular complications.

PMID- 29473789
TI  - Ligament augmentation for prevention of proximal junctional kyphosis and proximal
      junctional failure in adult spinal deformity.
AB  - OBJECTIVE Proximal junctional kyphosis (PJK) is a well-recognized, yet
      incompletely defined, complication of adult spinal deformity surgery. There is no
      standardized definition for PJK, but most studies describe PJK as an increase in
      the proximal junctional angle (PJA) of greater than 10 degrees -20 degrees .
      Ligament augmentation is a novel strategy for PJK reduction that provides
      strength to the upper instrumented vertebra (UIV) and adjacent segments while
      also reducing junctional stress at those levels. METHODS In this study, ligament
      augmentation was used in a consecutive series of adult spinal deformity patients
      at a single institution. Patient demographics, including age; sex; indication for
      surgery; revision surgery; surgical approach; and use of 3-column osteotomies,
      vertebroplasty, or hook fixation at the UIV, were collected. The PJA was measured
      preoperatively and at last follow-up using 36-inch radiographs. Data on change in
      PJA and need for revision surgery were collected. Univariate and multivariate
      analyses were performed to identify factors associated with change in PJA and
      proximal junctional failure (PJF), defined as PJK requiring surgical correction.
      RESULTS A total of 200 consecutive patients were included: 100 patients before
      implementation of ligament augmentation and 100 patients after implementation of
      this technique. The mean age of the ligament augmentation cohort was 66 years,
      and 67% of patients were women. Over half of these cases (51%) were revision
      surgeries, with 38% involving a combined anterior or lateral and posterior
      approach. The mean change in PJA was 6 degrees  in the ligament augmentation
      group compared with 14 degrees  in the control group (p < 0.001). Eighty-four
      patients had a change in PJA of less than 10 degrees . In a multivariate linear
      regression model, age (p = 0.016), use of hook fixation at the UIV (p = 0.045),
      and use of ligament augmentation (p < 0.001) were associated with a change in
      PJA. In a separate model, only ligament augmentation (OR 0.193, p = 0.012) showed
      a significant association with PJF. CONCLUSIONS Ligament augmentation represents
      a novel technique for the prevention of PJK and PJF. Compared with a well-matched
      historical cohort, ligament augmentation is associated with a significant
      decrease in PJK and PJF. These data support the implementation of ligament
      augmentation in surgery for adult spinal deformity, particularly in patients with
      a high risk of developing PJK and PJF.

PMID- 29473790
TI  - Extraforaminal approach of biportal endoscopic spinal surgery: a new endoscopic
      technique for transforaminal decompression and discectomy.
AB  - This study was performed to describe the extraforaminal approach of biportal
      endoscopic spinal surgery (BESS) as a new endoscopic technique for transforaminal
      decompression and discectomy and to demonstrate the clinical outcomes of this new
      procedure for the first time. Twenty-one patients (27 segments) who underwent the
      extraforaminal approach of BESS between March 2015 and April 2016 were enrolled
      according to the inclusion and exclusion criteria. The operative time
      (minutes/level) and complications after the procedure were recorded. The visual
      analog scale (VAS) score was checked to assess the degree of radicular leg pain
      preoperatively and at the time of the last follow-up. The modified Macnab
      criteria were used to examine the clinical outcomes at the time of the last
      follow-up. The mean duration of the follow-up period was 14.8 months (minimum
      duration 12 months). The mean operative time was 96.7 minutes for one level. The
      mean VAS score for radicular leg pain dropped from a preoperative score of 7.5 +/
      0.9 to a final follow-up score of 2.5 +/- 1.2 (p < 0.001). The final outcome
      according to the modified Macnab criteria was excellent in 5 patients (23.8%),
      good in 12 (57.2%), fair in 4 (19.0%), and poor in 0. Therefore, excellent or
      good results (a satisfied outcome) were obtained in 80.9% of the patients.
      Complications were limited to one dural tear (4.8%). The authors found that the
      extraforaminal approach of BESS was a feasible and advantageous endoscopic
      technique for the treatment of foraminal lesions, including stenosis and disc
      herniation. They suggest that this technique represents a useful, alternative,
      minimally invasive method that can be used to treat lumbar foraminal stenosis and
      disc herniation.

PMID- 29473791
TI  - First Report of an ST410 OXA-181 and CTX-M-15 Coproducing Escherichia coli Clone
      in Italy: A Whole-Genome Sequence Characterization.
AB  - We investigated an Italian OXA-181-producing Escherichia coli clinical isolate
      (ECS1_14) by whole-genome sequencing. The strain coharbored blaCTX-M-15, blaCMY
      2, and qnrS1 genes; it belonged to ST410(Achtman)/ST692(Pasteur) and phylogroup
      A. The blaOXA-181 gene was harbored on a plasmid highly similar (99% identity) to
      the pOXA181_EC14828 plasmid, recently reported in China.

PMID- 29473792
TI  - New Mutations of Penicillin-Binding Proteins in Streptococcus agalactiae Isolates
      from Cattle with Decreased Susceptibility to Penicillin.
AB  - Streptococcus agalactiae is a causal agent of bovine mastitis and is treated by
      beta-lactam antibiotics (BLAs). Compared to penicillin-resistant S. agalactiae
      from humans, resistant strains in bovine are rarely reported. In this study, we
      aimed to investigate BLA resistance and mutations in penicillin-binding proteins
      (PBPs) of S. agalactiae in central and northeast China. The minimum inhibitory
      concentrations (MICs) of 129 penicillin-resistant S. agalactiae isolates from
      cows with mastitis were determined, and the related PBP genes were detected and
      sequenced. All strains were unsusceptible to penicillin G and mostly resistant to
      ampicillin, cefalexin, and ceftiofur sodium. One hundred twenty-nine strains were
      divided into 4 clonal groups and 8 sequence types by multilocus sequence typing
      analysis. We found a set of new substitutions in PBP1B, PBP2B, and PBP2X from
      most strains isolated from three provinces. The strains with high PBP mutations
      showed a broader unsusceptible spectrum and higher MICs than those with few or
      single mutation. Our research indicates unpredicted mutations in the PBP genes of
      S. agalactiae isolated from cows with mastitis treated by BLAs. This screening is
      the first of S. agalactiae from cattle.

PMID- 29473795
TI  - Clinical commentary on 'Severe hypertriglyceridemia associated with teriflunomide
      in a patient with multiple sclerosis'.

PMID- 29473794
TI  - [Mutual guiding and following of movement - The interaction process in
      mobilisation based on the example of kinaesthetics: A qualitative study].
AB  - Background: Mobility impairment is often seen as a reason for needing long-term
      care. Thus, promoting mobility becomes increasingly significant in nursing homes.
      The kinaesthetic approach offers a way to support nursing home residents in using
      their own resources to maintain or improve their mobility. Aim: The present study
      intends to identify the characteristics of the interaction between nursing home
      residents with impaired mobility and kinaesthetic trainers during mobilisation.
      Methods: This secondary analysis comprises nine video sequences interpreted
      according to Grounded Theory-principles. The findings are described in a basic
      model. Results: The interaction with nursing home residents is focused on adapted
      movement support. This assistance shows a positive effect on residents' self
      activity in the tracking process and in the context of other strategies.
      Intervening conditions like residents' daily constitution have an influence on
      nurses' kinaesthetic strategies. Thereby, nurses have to be highly competent in
      self-perception. Conclusion: Adapted movement support proves to be a phenomenon
      basing on the nurse-resident-interaction and allowing residents to actively
      participate in collaborative action.

PMID- 29473796
TI  - Severe hypertriglyceridemia associated with teriflunomide in a patient with
      multiple sclerosis: A case report.
AB  - OBJECTIVE: To describe a case of severe hypertriglyceridemia in a patient
      receiving teriflunomide. METHODS: This is a case study. RESULTS: Our patient
      developed severe hypertriglyceridemia (>5000 mg/dL) while on teriflunomide. The
      drug was withdrawn. Resolution began over 3 weeks later. CONCLUSION: We describe
      the first probable case of teriflunomide-associated severe hypertriglyceridemia
      in a patient with multiple sclerosis, an adverse event previously associated with
      leflunomide in patients with rheumatologic diseases. Clinicians should be aware
      of this rare but potentially dangerous adverse event.

PMID- 29473797
TI  - Formation and inhibition of N-nitrosodiethanolamine in cosmetics under pH,
      temperature, and fluorescent, ultraviolet, and visual light.
AB  - N-nitrosodiethanolamine (NDELA), a type of nitrosamine, is a possible human
      carcinogen that may form in cosmetic products. The aim of this study was to
      examine the formation and inhibition of NDELA through chemical reactions of
      secondary amines including mono-ethanolamine, di-ethanolamine (DEA), and tri
      ethanolamine (TEA), and sodium nitrite (SN) under varying conditions such as pH,
      temperature, and fluorescent, ultraviolet (UV), and visual light (VIS) using
      liquid chromatography-mass spectroscopy. In a mixture of TEA and SN under acidic
      conditions pH 2, residual NDELA concentrations rose significantly under various
      storage conditions in the following order: 50 degrees C > 40 degrees C > UV (2
      W/m2) > VIS (4000 lux) > fluorescent light > 25 degrees C > 10 degrees C. In a
      mixture of DEA and SN under the same acidic pH 2 conditions, NDELA formation was
      significantly elevated in the following order: UV (2 W/m2) > VIS (4000 lux) > 50
      degrees C > 40 degrees C > fluorescent light > 25 degrees C > 10 degrees C.
      Inhibition of NDELA formation by d-mannitol, vitamin C (Vit C), or vitamin E (Vit
      E) was determined under varying conditions of pH, temperature, and fluorescent,
      UV, and VIS. At high concentrations of 100 or 1000 ug/ml, Vit E significantly
      decreased residual NDELA compared with control levels under acidic pH 2, but not
      under basic pH 6. Among various antioxidants, Vit E reacted more effectively with
      many nitrosating agents such as nitrate and nitrite found in cosmetic products.
      Therefore, to reduce NDELA, it is recommended that cosmetics be stored under
      cool/amber conditions and that Vit E or Vit C inhibitors of nitrosation be
      optimally added to cosmetic formulations at concentrations between 100 and 1000
      ug/ml.

PMID- 29473798
TI  - Cytochrome P450 1B1 promotes cancer cell survival via specificity protein 1 (Sp1)
      mediated suppression of death receptor 4.
AB  - Cytochrome P450 1B1 (CYP1B1), a well-known oncogene, has garnered wide attention
      because of its tumor-specific expression pattern and actions as a carcinogenic
      factor. Although CYP1B1 might play a crucial role in carcinogenesis, the detailed
      molecular mechanisms underlying oncogenic involvement in cancer development
      remain unclear. The present study investigated the manner in which CYP1B1
      promotes survival of various cancer cells. Treatment with 2,2',4,6'
      tetramethoxystilbene (TMS), a specific CYP1B1 inhibitor, significantly inhibited
      cell viability in human breast cancer and leukemia cell lines, including MCF-7,
      MDA-MB-231, HL-60, and U937 cells. In order to characterize the cellular
      functions of CYP1B1 associated with cancer cell survival, the relationship
      between this oncogene and death receptor 4 (DR4) was determined. Following
      induction or inhibition of CYP1B1, mRNA and protein expression levels of DR4 were
      measured, and this oncogene was found to significantly repress DR4 mRNA and
      protein expression. Further, the suppression of DR4 by CYP1B1 was restored with 5
      aza-2'-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, indicating
      that DNA methylation may be involved in CYP1B1-mediated DR4 inhibition.
      Methylation-specific polymerase chain reaction (PCR) in CYP1B1-overexpressed HL
      60 cells revealed that this oncogene induced hypermethylation on DR4 promoter.
      Interestingly, data showed that DR4 suppression of CYP1B1 is mediated by the DNA
      binding ability of specificity protein 1 (Sp1). These findings suggest that
      CYP1B1 promotes cancer cell survival through involvement of DNA methylation
      mediated DR4 inhibition and that Sp1 may act as key mediator required for
      oncogenic action.

PMID- 29473799
TI  - Learning, memory deficits, and impaired neuronal maturation attributed to
      acrylamide.
AB  - Acrylamide (ACR) is a neurotoxin known to produce neurotoxicity characterized by
      ataxia, skeletal muscle weakness, cognitive impairment, and numbness of the
      extremities. Previously, investigators reported that high-dose (50 mg/kg) ACR
      impaired hippocampal neurogenesis and increased neural progenitor cell death;
      however, the influence of subchronic environmentally relevant low dose-(2, 20, or
      200 MUg/kg) ACRs have not been examined in adult neurogenesis or cognitive
      function in mice. Accordingly, the aim of the present study was to investigate
      whether low-dose ACR adversely affected mouse hippocampal neurogenesis and
      neurocognitive functions. Male C57BL/6 mice were orally administered vehicle or
      ACR at 2, 20, or 200 MUg/kg/day for 4 weeks. ACR did not significantly alter the
      number of newly generated cells or produce neuroinflammation or neuronal loss in
      hippocampi. However, behavioral studies revealed that 200 MUg/kg ACR produced
      learning and memory impairment. Furthermore, incubation of ACR with primary
      cultured neurons during the developmental stage was found to delay neuronal
      maturation without affecting cell viability indicating the presence of
      developmental neurotoxicity. These findings indicate that although exposure to in
      vivo low-dose ACR daily for 4 weeks exerted no apparent marked effect on
      hippocampal neurogenesis, in vitro observations in primary cultured neurons noted
      adverse effects on learning and memory impairment suggestive of neurotoxic
      actions.

PMID- 29473801
TI  - Moot Court Best Brief Winner 2015.

PMID- 29473800
TI  - A beta-galactosidase-expressing E. coli culture as an alternative test to
      identify skin sensitizers and non-sensitizers.
AB  - Although the Organization for Economic Cooperation and Development (OECD) has
      adopted several in vitro methods with reasonable predictive capacity, alternative
      methods for identifying skin sensitizers and non-sensitizers with reliability and
      simplicity are still required for more efficient and economic prediction. The
      present study was to design an in vitro system with the use of a beta
      galactosidase-expressing E. coli culture for simpler but sufficiently accurate
      classification of skin sensitizers and non-sensitizers. A LacZ gene-containing E.
      coli strain that is capable of producing beta-galactosidase enzyme was induced by
      isopropyl beta-D-1-thiogalactopyranoside with concomitant treatment with test
      chemicals. After 6-hr incubation, cells were lysed and beta-galactosidase enzyme
      activity was monitored colorimetrically by using O-nitrophenyl-D
      galactopyranoside as a substrate. Following optimization of several experimental
      conditions, 22 skin sensitizers and 11 non-sensitizers were examined to assess
      predictive capacity of this method. The results indicated that predictivity was
      as follows: 90.9% sensitivity, 81.8% specificity, and 87.9% accuracy, when 17.3%
      of control activity was used as the cut-off value to separate sensitizers from
      non-sensitizers. Data suggested that the current bacterial system expressing beta
      galactosidase may serve as a useful alternative test for classifying skin
      sensitizers and non-sensitizers, without the utilization of animals or mammalian
      cell cultures.

PMID- 29473804
TI  - Can They Do That?: The Limits of Governmental Power over Medical Treatment.

PMID- 29473803
TI  - Messy but Fair: The ACA's Hospital Value-Based Purchasing Program and the Notice
      and-Comment Process.
AB  - The Centers for Medicare and Medicaid Services (CMS) promulgated a new Medicare
      program called the Value-Based Purchasing Program (VBPP) as part of the 2010
      Affordable Care Act (ACA). Like many other regulatory agencies, CMS used the
      Notice-and-Comment process to issue proposed rules, solicit public comments, and
      then publish final rules. Conventional literature suggests that CMS should
      disproportionately favor business interests during the Notice-and-Comment
      process, mainly due to the business interests' greater resources and capacity to
      draft well-reasoned comments. However, this article argues against this
      presumption and contends instead that CMS listens equally well to both business
      interest comments and private citizen comments during the formation of the VBPP.
      With regard to the VBPP and the ACA, CMS appears to be resisting disproportionate
      sway by business interests and is instead privileging the ACA's goal of improving
      healthcare quality.

PMID- 29473805
TI  - The Need to Repeal Certificate of Need Laws to Improve America's Health Care
      System: A Dormant Commerce Clause Analysis.

PMID- 29473806
TI  - Constitutional Implications of Vaccine Exemption Laws: Introduction to the 2015
      2016 National Health Law Moot Court Competition Problem.

PMID- 29473807
TI  - 2015-2016 Southern Illinois University National Health Law Moot Court
      Competition.

PMID- 29473808
TI  - Can Requiring a Woman to Obtain the Consent of the Father before Receiving an
      Abortion Really Be Constitutional? Brief Answer: No.

PMID- 29473809
TI  - Postpartum Illness and Sentencing: Why the Insanity Defense Is Not Enough for
      Mothers with Postpartum Depression, Anxiety, and Psychosis.

PMID- 29473810
TI  - Brain Death Forsaken: Growing Conflict and New Legal Challenges.

PMID- 29473811
TI  - Lost World: Discovering Medical Antitrust Law's Uses and Abuses.

PMID- 29473812
TI  - Acquired Immunodeficiency Syndrome A Forensic Perspective.
AB  - This article provides a review of the science of HIV/AIDS for nonspecialist
      stakeholders such as lawyers, regulators, and policy analysts. The purpose of the
      article is twofold: it (1) aims to communicate the biomedical principles that
      underlie the pandemic in a rigorous yet accessible format and (2) shows that an
      understanding of the interaction between a legal rule and medical science is
      essential if the intended meaning, purpose, and policy rationale of the rule are
      to be preserved. It illustrates the interaction between law and science by
      analyzing the application of a doctrine in medical malpractice to litigation
      involving HIV/AIDS. It then draws parallels to other emerging diseases and shows
      how the analysis can be generalized and extended to legal issues involving any
      novel disease.

PMID- 29473813
TI  - Tubular approach to minimally invasive microdiscectomy for pediatric lumbar disc
      herniation.
AB  - OBJECTIVE Lumbar disc herniation (LDH) in the pediatric population is rare and
      exhibits unique characteristics compared with adult LDH. There are limited data
      regarding the safety and efficacy of minimally invasive surgery (MIS) using
      tubular retractors in pediatric patients with LDH. Here, the outcomes of MIS
      tubular microdiscectomy for the treatment of pediatric LDH are evaluated. METHODS
      Twelve consecutive pediatric patients with LDH were treated with MIS tubular
      microdiscectomy at the authors' institution between July 2011 and October 2015.
      Data were gathered from retrospective chart review and from mail or electronic
      questionnaires. The Macnab criteria and the Oswestry Disability Index (ODI) were
      used for outcome measurements. RESULTS The mean age at surgery was 17 +/- 1.6
      years (range 13-19 years). Seven patients were female (58%). Prior to surgical
      intervention, 100% of patients underwent conservative treatment, and 50% had
      epidural steroid injections. Preoperative low-back and leg pain, positive
      straight leg raise, and myotomal leg weakness were noted in 100%, 83%, and 67% of
      patients, respectively. The median duration of symptoms prior to surgery was 9
      months (range 1-36 months). The LDH level was L5-S1 in 75% of patients and L4-5
      in 25%. The mean +/- SD operative time was 90 +/- 21 minutes, the estimated blood
      loss was <= 25 ml in 92% of patients (maximum 50 ml), and no intraoperative or
      postoperative complications were noted at 30 days. The median hospital length of
      stay was 1 day (range 0-3 days). The median follow-up duration was 2.2 years
      (range 0-5.8 years). One patient experienced reherniation at 18 months after the
      initial operation and required a second same-level MIS tubular microdiscectomy to
      achieve resolution of symptoms. Of the 11 patients seen for follow-up, 10
      patients (91%) reported excellent or good satisfaction according to the Macnab
      criteria at the last follow-up. Only 1 patient reported a fair level of
      satisfaction by using the same criteria. Seven patients completed an ODI
      evaluation at the last follow-up. For these 7 patients, the mean ODI low-back
      pain score was 19.7% (SEM 2.8%). CONCLUSIONS To the authors' knowledge, this is
      the longest outcomes study and the largest series of pediatric patients with LDH
      who were treated with MIS microdiscectomy using tubular retractors. These data
      suggest that MIS tubular microdiscectomy is safe and efficacious for pediatric
      LDH. Larger prospective cohort studies with longer follow-up are needed to better
      evaluate the long-term efficacy of MIS tubular microdiscectomy versus other open
      and MIS techniques for the treatment of pediatric LDH.

PMID- 29473814
TI  - Restoration of shoulder motion using single- versus dual-nerve repair in
      obstetrical brachial plexus injury.
AB  - OBJECTIVE The purpose of this study was to compare shoulder abduction and
      external rotation (ER) after single-nerve repair of the upper trunk alone versus
      dual-nerve repair of both the upper trunk and the suprascapular nerve. METHODS A
      retrospective chart review of a single surgeon's experience repairing obstetrical
      brachial plexus injuries between June 1995 and June 2015 was performed. Eight
      patients underwent repair of the upper trunk alone, and 10 patients underwent
      repair of the upper trunk and the suprascapular nerve. Shoulder abduction and ER
      ranges of motion (ROMs) (in degrees) were recorded preoperatively and
      postoperatively. Postoperative ROM and the difference in ROM gained after surgery
      were compared by independent t-test analysis. RESULTS The mean follow-up time was
      161.4 weeks (range 62-514 weeks, SD 124.0 weeks). The mean patient age at the
      time of surgery was 31.3 weeks (range 19.9-47.0 weeks, SD 6.9 weeks). The mean
      postoperative shoulder abduction ROMs were 145.0 degrees  (range 85 degrees -180
      degrees , SD 39.4 degrees ) after single-nerve repair and 134.0 degrees  (range
      90 degrees -180 degrees , SD 30.3 degrees ) after dual-nerve repair (p = 0.51).
      The mean postoperative shoulder ER ROMs were 67.5 degrees  (range 10 degrees -95
      degrees , SD 28.8 degrees ) after single-nerve repair and 72.0 degrees  (range 10
      degrees -95 degrees , SD 31.3 degrees ) after dual-nerve repair (p = 0.76).
      CONCLUSIONS The authors found no difference in shoulder abduction and ER between
      patients who underwent single-nerve repair of the upper trunk alone and those who
      underwent dual-nerve repair of both the upper trunk and the suprascapular nerve.

PMID- 29473815
TI  - Incidence of symptomatic tethered spinal cord in pediatric patients presenting
      with neurofibromatosis types 1 and 2.
AB  - OBJECTIVE The relationship between a tethered cord (TC) and neurofibromatosis
      type 1 (NF1) and NF2 is not known. The purpose of this study was to define the
      incidence of TC in pediatric neurosurgical patients who present with NF. METHODS
      The authors performed a single-institution (tertiary care pediatric hospital) 10
      year retrospective analysis of patients who were diagnosed with or who underwent
      surgery for a TC and/or NF. Clinical and radiological characteristics were
      analyzed, as was histopathology. RESULTS A total of 424 patients underwent
      surgery for a TC during the study period, and 67 patients with NF were seen in
      the pediatric neurosurgery clinic. Of these 67 patients, 9 (13%) were diagnosed
      with a TC, and filum lysis surgery was recommended. Among the 9 patients with NF
      recommended for TC-release surgery, 4 (44%) were female, the mean age was 8 years
      (range 4-14 years), the conus position ranged from L1-2 to L-3, and 3 (33%) had a
      filum lipoma, defined as high signal intensity on T1-weighted MR images. All 9 of
      these patients presented with neuromotor, skeletal, voiding, and/or pain-related
      symptoms. Histopathological examination consistently revealed dense
      fibroconnective tissue and blood vessels. CONCLUSIONS Despite the lack of any
      known pathophysiological relationship between NF and TC, the incidence of a
      symptomatic TC in patients with NF1 and NF2 who presented for any reason to this
      tertiary care pediatric neurosurgery clinic was 13%. Counseling patients and
      families regarding TC symptomatology might be indicated in this patient
      population.

PMID- 29473816
TI  - DNA methylation signatures of pulmonary arterial smooth muscle cells in chronic
      thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening
      disease, which is often underpinned by vascular remodeling. Pulmonary arterial
      smooth muscle cells (PASMCs) are the main participants in vascular remodeling.
      However, their biological role in CTEPH is not entirely clear. In the present
      study, we analyzed the whole epigenome-wide DNA methylation profile of cultured
      PASMCs from CTEPH and control cell lines with the Illumina Human Methylation 450K
      BeadChip. A total of 6,829 significantly differentially methylated probes (DMPs)
      were detected between these two groups. Among these, 4,246 DMPs were
      hypermethylated, while 2,583 DMPs were hypomethylated. The functional enrichment
      analysis of 1,743 DMPs in the promoter regions and corresponding genes indicated
      that DNA hypermethylation and hypomethylation might be involved in the regulation
      of genes that have multifarious biological roles, including roles in cancer
      related diseases, the regulation of the actin cytoskeleton, cell adhesion, and
      pattern specification processes. The observed methylations were categorized into
      the most important functions, including those involved in cell proliferation,
      immunity, and migration. We speculate that these methylations were most likely
      involved in the possible pathophysiology of CTEPH. Gene interaction analysis
      pertaining to signal networks confirmed that PIK3CA and PIK3R1 were important
      mediators in these whole networks. The mRNA levels of PIK3CA, HIC1, and SSH1 were
      verified by qPCR and corresponded with DNA methylation differences. Understanding
      epigenetic features associated with CTEPH may provide new insights into the
      mechanism that underlie this condition.

PMID- 29473817
TI  - Na+/H+ exchanger isoform 1-induced osteopontin expression facilitates cardiac
      hypertrophy through p90 ribosomal S6 kinase.
AB  - Cardiovascular diseases are the leading cause of death worldwide. One in three
      cases of heart failure is due to dilated cardiomyopathy. The Na+/H+ exchanger
      isoform 1 (NHE1), a multifunctional protein and the key pH regulator in the
      heart, has been demonstrated to be increased in this condition. We have
      previously demonstrated that elevated NHE1 activity induced cardiac hypertrophy
      in vivo. Furthermore, the overexpression of active NHE1 elicited modulation of
      gene expression in cardiomyocytes including an upregulation of myocardial
      osteopontin (OPN) expression. To determine the role of OPN in inducing NHE1
      mediated cardiomyocyte hypertrophy, double transgenic mice expressing active NHE1
      and OPN knockout were generated and assessed by echocardiography and the cardiac
      phenotype. Our studies showed that hearts expressing active NHE1 exhibited
      cardiac remodeling indicated by increased systolic and diastolic left ventricular
      internal diameter and increased ventricular volume. Moreover, these hearts
      demonstrated impaired function with decreased fractional shortening and ejection
      fraction. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)
      mRNA was upregulated, and there was an increase in heart cell cross-sectional
      area confirming the cardiac hypertrophic effect. Moreover, NHE1 transgenic mice
      also showed increased collagen deposition, upregulation of CD44 and
      phosphorylation of p90 ribosomal s6 kinase (RSK), effects that were regressed in
      OPN knockout mice. In conclusion, we developed an interesting comparative model
      of active NHE1 transgenic mouse lines which express a dilated hypertrophic
      phenotype expressing CD44 and phosphorylated RSK, effects which were regressed in
      absence of OPN.

PMID- 29473818
TI  - Transcriptomic sequencing reveals diverse adaptive gene expression responses of
      human vascular smooth muscle cells to nitro-conjugated linoleic acid.
AB  - Nitro-conjugated linoleic acid (NO2-CLA) is formed by metabolic and inflammatory
      reactions of nitric oxide and nitrite, and represents the most abundant nitro
      fatty acid species in humans. These electrophilic fatty acid nitroalkene
      derivatives mediate pleiotropic cell signaling responses. Here, we report a
      systematic approach to investigate the effect of NO2-CLA on human coronary artery
      smooth muscle cells (hCASMC), based on the RNA-Seq and bioinformatics analysis.
      There were extensive differentially expressed genes in NO2-CLA vs. control (510)
      and NO2-CLA vs. CLA (272) treatment groups, respectively. Notably, only minimal
      alterations were observed in CLA vs. control conditions, indicating that the
      electrophilic character of NO2-CLA is requited to induce differential gene
      expression responses independently from native CLA. Functional enrichment
      analysis of differentially expressed genes reveals multiple cellular processes to
      be affected under NO2-CLA treatment, including cell proliferation, lipid
      metabolism, antioxidant and inflammatory-related gene expression responses. These
      findings reveal that nitro-fatty acid derivatives such as NO2-CLA regulate a
      broad array of adaptive gene expression responses by hCASMC.

PMID- 29473820
TI  - Transcriptional profiling of the clpX mutant in Bacillus anthracis reveals
      regulatory connection with the lrgAB operon.
AB  - ClpX functions as either an independent chaperone or a component of the ClpXP
      protease, a conserved intracellular protease that acts as a global regulator in
      the bacterial cell by degrading regulatory proteins, stress response proteins and
      rate-limiting enzymes. Previously, we found that loss of clpX in Bacillus
      anthracis Sterne leads to increased susceptibility to antimicrobial agents that
      target the cell envelope. The aim of this study was to identify genes within the
      regulatory network of clpX that contribute to antimicrobial resistance. Using
      microarray analysis, we found 119 genes that are highly differentially expressed
      in the ?clpX mutant, with the majority involved in metabolic, transport or
      regulatory functions. Several of these differentially expressed genes, including
      glpF, sigM, mrsA, lrgA and lrgB, are associated with cell wall-active antibiotics
      in other bacterial species. We focused on lrgA and lrgB, which form the lrgAB
      operon and are downregulated in ?clpX, because loss of lrgAB increases autolytic
      activity and penicillin susceptibility in Staphylococcus aureus. While we
      observed no changes in autolytic activity in either ?clpX or ?lrgAB B. anthracis
      Sterne, we find that both mutants have increased susceptibility to the
      antimicrobial peptide LL-37 and daptomycin. However, phenotypes between ?clpX and
      ?lrgAB are not identical as ?clpX also displays increased susceptibility to
      penicillin and nisin but ?lrgAB does not. Therefore, while decreased expression
      of lrgAB may be partially responsible for the increased antimicrobial
      susceptibility seen in the ?clpX mutant, disruption of other pathways must also
      contribute to this phenotype.

PMID- 29473819
TI  - Comamonas aquatilis sp. nov., isolated from a garden pond.
AB  - A beige-pigmented bacterial strain, SB30-Chr27-3T, isolated from a garden pond,
      was studied for its taxonomic position. Cells of the isolate were rod-shaped and
      stained Gram-negative. A comparison of the 16S rRNA gene sequence with the
      sequences of the type strains of the most closely related species showed that the
      strain belongs to the genus Comamonas and showed highest sequence similarities to
      the type strains of Comamonas jiangduensis (97.5 %), Comamonas aquatica (97.4 %)
      and Comamonas phosphati (97.3 %). The 16S rRNA gene sequence similarities to all
      other Comamonas species were below 97.0 %. The fatty acid profile of strain SB30
      Chr27-3T consisted of the major fatty acids C16 : 0, C15 : 0iso 2-OH/ C16 :
      1omega7c, C18 : 1omega7c/C18 : 1omega9c and, in a minor amount, C10 : 0 3-OH.
      Major compounds in the polar lipid profile were phosphatidylethanolamine,
      phosphatidylglycerol, phosphatidylserine and diphosphatidylglycerol. The quinone
      system was exclusively composed of ubiquinone Q-8. The polyamine pattern
      contained the major compounds putrescine, cadaverine and 2-hydroxyputrescine.
      These data and the differentiating biochemical properties indicated that isolate
      SB30-CHR27-3T represents a novel species of the genus Comamonas, for which we
      propose the name >Comamonas aquatilis sp. nov. with the type strain SB30-Chr27-3T
      (=CIP 111491T=CCM 8815T).

PMID- 29473822
TI  - RgsA, an RpoS-dependent sRNA, negatively regulates rpoS expression in Pseudomonas
      aeruginosa.
AB  - As a master regulator, the alternative sigma factor RpoS coordinates the
      transcription of genes associated with protection against environmental stresses
      in bacteria. In Pseudomonas aeruginosa, RpoS is also involved in quorum sensing
      and virulence. The cellular RpoS level is regulated at multiple levels, whereas
      the post-transcriptional regulation of rpoS in P. aeruginosa remains unclear. To
      identify and characterize small regulatory RNAs (sRNAs) regulating RpoS in P.
      aeruginosa, an sRNA library expressing a total of 263 sRNAs was constructed to
      examine their regulatory roles on rpoS expression. Our results demonstrate that
      rpoS expression is repressed by the RpoS-dependent sRNA RgsA at the post
      transcriptional level. Unlike OxyS, an sRNA previously known to repress rpoS
      expression under oxidative stress in Escherichia coli, RgsA represses rpoS
      expression during the exponential phase. This repression requires the RNA
      chaperone Hfq. Furthermore, the 71-77 conserved region of RgsA is necessary for
      full repression of rpoS expression, and the -25 to +27 region of rpoS mRNA is
      sufficient for RgsA-mediated rpoS repression. Together, our results not only add
      RgsA to the RpoS regulatory circuits but also highlight the complexity of
      interplay between sRNAs and transcriptional regulators in bacteria.

PMID- 29473821
TI  - Luteimonas rhizosphaerae sp. nov., isolated from the rhizosphere of Triticum
      aestivum L.
AB  - A Gram-stain-negative, rod-shaped bacterium, strain 4-12T, was isolated from the
      rhizosphere of Triticum aestivum L. from the Xiaokai River irrigation area,
      China. The isolate grew optimally at 30  degrees C, pH 7.5-8.0 and with 1.0 %
      (w/v) NaCl. Based on the 16S rRNA gene sequence and phylogenetic analysis, strain
      4-12T belonged to the genus Luteimonas with the highest degree of 16S rRNA gene
      sequence similarity to Luteimonas tolerans UM1T (97.68 %), followed by Luteimonas
      terrae THG-MD21T (97.67 %), Lysobacter panaciterrae Gsoil 068T (97.21 %) and
      Luteimonas aestuarii B9T (97.16 %). However, the DNA-DNA relatedness values
      between strain 4-12T and closely related Luteimonas strains were well below 40 %.
      The average nucleotide identity and the Genome-to-Genome Distance Calculator also
      showed low relatedness (below 95 and 70 %, respectively) between strain 4-12T and
      the type strains in genus Luteimonas. Ubiquinone-8 was the predominant quinone.
      The major fatty acids were iso-C15 : 0, iso-C11 : 0, iso-C17 : 0 and iso-C17 :
      1omega9c. Polar lipids were dominated by diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol and unidentified phospholipids.
      The DNA G+C content was 69.5 %. According to the phenotypic, genetic and
      chemotaxonomic data, strain 4-12T is considered to represent a novel species in
      the genus Luteimonas, for which the name >Luteimonas rhizosphaerae sp. nov. is
      proposed, with strain 4-12T (=CCTCC AB 2016261T=KCTC 52585T) as the type strain.

PMID- 29473823
TI  - Effect of structural evolution of ZnO/HfO2 nanocrystals on Eu2+/Eu3+ emission in
      glass-ceramic waveguides for photonic applications.
AB  - Eu-doped 70SiO2-23HfO2-7ZnO (mol%) glass-ceramic waveguides have been fabricated
      by sol-gel method as a function of heat-treatment temperatures for on-chip blue
      light emitting source applications. Structural evolution of spherical ZnO and
      spherical as well as rod-like HfO2 nanocrystalline structures have been observed
      with heat-treatments at different temperatures. Initially, in the as-prepared
      samples at 900 ?C, both, Eu2+ as well as Eu3+ ions are found to be present in the
      ternary matrix. With controlled heat-treatments of up to 1000 ?C for 2 h, local
      environment of Eu-ions become more crystalline in nature and the reduction of
      Eu3+ to Eu2+ takes place in such ZnO/HfO2 crystalline environments. In these
      ternary glass-ceramic waveguides, heat-treated at higher temperatures, the blue
      light emission characteristic, which is the signature of 4f 65d [Formula: see
      text] 4f 7 energy level transition of Eu2+ ions is found to be greatly enhanced.
      The as-prepared glass-ceramic waveguides exhibit a propagation loss of 0.4 +/-
      0.2 dB cm-1 at 632.8 nm. Though the propagation losses increase with the growth
      of nanocrystals, the added functionalities achieved in the optimally heat-treated
      Eu-doped 70SiO2-23HfO2-7ZnO (mol%) waveguides, make them a viable functional
      optical material for the fabrication of on-chip blue-light emitting sources for
      integrated optic applications.

PMID- 29473824
TI  - Insufficiency of the Young's modulus for illustrating the mechanical behavior of
      GaN nanowires.
AB  - We use a non-classical modified couple stress theory including the acceleration
      gradients (MCST-AG), to precisely demonstrate the size dependency of the
      mechanical properties of gallium nitride (GaN) nanowires (NWs). The fundamental
      elastic constants, Young's modulus and length scales of the GaN NWs were
      estimated both experimentally, using a novel experimental technique applied to
      atomic force microscopy, and theoretically, using atomic simulations. The Young's
      modulus, static and the dynamic length scales, calculated with the MCST-AG, were
      found to be 323 GPa, 13 and 14.5 nm, respectively, for GaN NWs from a few
      nanometers radii to bulk radii. Analyzing the experimental data using the
      classical continuum theory shows an improvement in the experimental results by
      introducing smaller error. Using the length scales determined in MCST-AG, we
      explain the inconsistency of the Young's moduli reported in recent literature,
      and we prove the insufficiency of the Young's modulus for predicting the
      mechanical behavior of GaN NWs.

PMID- 29473825
TI  - Generation and detection of dissipationless spin current in a MgO/Si bilayer.
AB  - Spintronics is an analogue to electronics where the spin of the electron rather
      than its charge is functionally controlled for devices. The generation and
      detection of spin current without ferromagnetic or exotic/scarce materials are
      two of the biggest challenges for spintronics devices. In this study, we report a
      solution to the two problems of spin current generation and detection in Si.
      Using non-local measurement, we experimentally demonstrate the generation of
      helical dissipationless spin current using the spin-Hall effect. Contrary to the
      theoretical prediction, we observe the spin-Hall effect in both n-doped and p
      doped Si. The helical spin current is attributed to the site-inversion asymmetry
      of the diamond cubic lattice of Si and structure inversion asymmetry in a MgO/Si
      bilayer. The spin to charge conversion in Si is insignificant due to weak spin
      orbit coupling. For the efficient detection of spin current, we report spin to
      charge conversion at the MgO (1 nm)/Si (2 um) (p-doped and n-doped) thin film
      interface due to Rashba spin-orbit coupling. We detected the spin current at a
      distance of  >100 um, which is an order of magnitude larger than the longest spin
      diffusion length measured using spin injection techniques. The existence of spin
      current in Si is verified from the coercivity reduction in a Co/Pd multilayer due
      to spin-orbit torque generated by spin current from Si.

PMID- 29473826
TI  - MoS2: a two-dimensional hole-transporting material for high-efficiency, low-cost
      perovskite solar cells.
AB  - In this work MoS2 thin film was studied as a potential two-dimensional (2D) hole
      transporting material for fabrication of low-cost, durable and efficient
      perovskite solar cells. The thickness of MoS2 was studied as a potential factor
      in reaching high power conversion efficiency in perovskite solar cells. The
      thickness of the perovskite layer and the different metal back contacts gave
      distinct photovoltaic properties to the designed cells. The results show that a
      single sheet of MoS2 could considerably improve the power conversion efficacy of
      the device from 10.41% for a hole transport material (HTM)-free device to 20.43%
      for a device prepared with a 0.67 nm thick MoS2 layer as a HTM. On the back, Ag
      and Al collected the carriers more efficiently than Au due to the value of their
      metal contact work function with the TiO2 conduction band. The present work
      proposes a new architecture for the fabrication of low-cost, durable and
      efficient perovskite solar cells made from a low-cost and robust inorganic HTM
      and electron transport material.

PMID- 29473827
TI  - Absence of a long-range ordered magnetic ground state in Pr3Rh4Sn13 studied
      through specific heat and inelastic neutron scattering.
AB  - Signatures of absence of a long-range ordered magnetic ground state down to 0.36
      K are observed in magnetic susceptibility, specific heat, thermal/electrical
      transport and inelastic neutron scattering data of the quasi-skutterudite
      compound Pr3Rh4Sn13 which crystallizes in the Yb3Rh4Sn13-type structure with a
      cage-like network of Sn atoms. In this structure, Pr3+ occupies a lattice site
      with D 2d point symmetry having a ninefold degeneracy corresponding to J  =  4.
      The magnetic susceptibility of Pr3Rh4Sn13 shows only a weak temperature
      dependence below 10 K; otherwise remaining paramagnetic-like in the range, 10 K
      300 K. From the inelastic neutron scattering intensity of Pr3Rh4Sn13 recorded at
      different temperatures, we identify excitations at 4.5(7) K, 5.42(6) K, 10.77(5)
      K, 27.27(5) K, 192.28(4) K and 308.33(3) K through a careful peak analysis.
      However, no signatures of long-range magnetic order are observed in the neutron
      data down to 1.5 K, which is also confirmed by the specific heat data down to
      0.36 K. A broad Schottky-like peak is recovered for the magnetic part of the
      specific heat, C 4f, which suggests the role of crystal electric fields of Pr3+ .
      A crystalline electric field model consisting of 7 levels was applied to C 4f
      which leads to the estimation of energy levels at 4.48(2) K, 6.94(4) K, 11.23(8)
      K, 27.01(5) K, 193.12(6) K and 367.30(2) K. The CEF energy levels estimated from
      the heat capacity analysis are in close agreement with the excitation energies
      seen in the neutron data. The Sommerfeld coefficient estimated from the analysis
      of magnetic specific heat is [Formula: see text] mJ K-2 mol-Pr which suggests the
      formation of heavy itinerant quasi-particles in Pr3Rh4Sn13. Combining inelastic
      neutron scattering results, analysis of the specific heat data down to 0.36 K,
      magnetic susceptibility and, electrical and thermal transport, we establish the
      absence of long-range ordered magnetic ground state in Pr3Rh4Sn13.

PMID- 29473828
TI  - Strain-induced tunable negative differential resistance in triangle graphene
      spirals.
AB  - Using non-equilibrium Green's function formalism combined with density functional
      theory calculations, we investigate the significant changes in electronic and
      transport properties of triangle graphene spirals (TGSs) in response to external
      strain. Tunable negative differential resistance (NDR) behavior is predicted. The
      NDR bias region, NDR width, and peak-to-valley ratio can be well tuned by
      external strain. Further analysis shows that these peculiar properties can be
      attributed to the dispersion widths of the p z orbitals. Moreover, the
      conductance of TGSs is very sensitive to the applied stress, which is promising
      for applications in nanosensor devices. Our findings reveal a novel approach to
      produce tunable electronic devices based on graphene spirals.

PMID- 29473829
TI  - Ion transport by gating voltage to nanopores produced via metal-assisted chemical
      etching method.
AB  - In this work, we report a simple and low-cost way to create nanopores that can be
      employed for various applications in nanofluidics. Nano sized Ag particles in the
      range from 1 to 20 nm are formed on a silicon substrate with a de-wetting method.
      Then the silicon nanopores with an approximate 15 nm average diameter and 200 MUm
      height are successfully produced by the metal-assisted chemical etching method.
      In addition, electrically driven ion transport in the nanopores is demonstrated
      for nanofluidic applications. Ion transport through the nanopores is observed and
      could be controlled by an application of a gating voltage to the nanopores.

PMID- 29473830
TI  - Stability investigation of a high number density Pt1/Fe2O3 single-atom catalyst
      under different gas environments by HAADF-STEM.
AB  - Catalysis by supported single metal atoms has demonstrated tremendous potential
      for practical applications due to their unique catalytic properties. Unless they
      are strongly anchored to the support surfaces, supported single atoms, however,
      are thermodynamically unstable, which poses a major obstacle for broad
      applications of single-atom catalysts (SACs). In order to develop strategies to
      improve the stability of SACs, we need to understand the intrinsic nature of the
      sintering processes of supported single metal atoms, especially under various gas
      environments that are relevant to important catalytic reactions. We report on the
      synthesis of high number density Pt1/Fe2O3 SACs using a facial strong adsorption
      method and the study of the mobility of these supported Pt single atoms at 250 
      degrees C under various gas environments that are relevant to CO oxidation, water
      gas shift, and hydrogenation reactions. Under the oxidative gas environment,
      Fe2O3 supported Pt single atoms are stable even at high temperatures. The
      presence of either CO or H2 molecules in the gas environment, however,
      facilitates the movement of the Pt atoms. The strong interaction between CO and
      Pt weakens the binding between the Pt atoms and the support, facilitating the
      movement of the Pt single atoms. The dissociation of H2 molecules on the Pt atoms
      and their subsequent interaction with the oxygen species of the support surfaces
      dislodge the surface oxygen anchored Pt atoms, resulting in the formation of Pt
      clusters. The addition of H2O molecules to the CO or H2 significantly accelerates
      the sintering of the Fe2O3 supported Pt single atoms. An anchoring-site
      determined sintering mechanism is further proposed, which is related to the metal
      support interaction.

PMID- 29473831
TI  - Understanding the Importance of the Teres Minor for Shoulder Function: Functional
      Anatomy and Pathology.
AB  - Although the teres minor is often overlooked in a normal shoulder, it becomes a
      key component in maintaining shoulder function when other rotator cuff tendons
      fail. The teres minor maintains a balanced glenohumeral joint and changes from an
      insignificant to the most significant external rotator in the presence of major
      rotator cuff pathology. The presence or absence of the teres minor provides
      prognostic information on the outcomes of reverse total shoulder arthroplasty and
      tendon transfers. Clinical tests include the Patte test, the Neer dropping sign,
      the external rotation lag sign, and the Hertel drop sign. Advanced imaging of the
      teres minor can be used for classification using the Walch system. Understanding
      the function and pathology surrounding the teres minor is paramount in
      comprehensive management of the patient with shoulder pathology. Appropriate
      clinical examination and imaging of the teres minor are important for
      preoperative stratification and postoperative expectations.

PMID- 29473832
TI  - Motocross Injuries in Pediatric and Adolescent Patients.
AB  - Motocross is a popular sport in which participants ride a two-wheeled, motorized
      vehicle on an uneven 2-km track with natural or human-made obstacles.
      Participants compete at high rates of speed, and children as young as age 4 years
      compete in age-appropriate groups. Motocross is recognized as a strenuous sport
      with a high accident rate. Most injuries are musculoskeletal in nature. The most
      commonly injured areas are the forearm, clavicle, femur, and tibia. Many injuries
      require surgical treatment. Some patients sustain head trauma with loss of
      consciousness. Children should have age-appropriate training before participation
      is allowed. Adult supervision should occur at all times. Appropriate helmet
      fitting with assistance from an expert is associated with a decreased risk of
      concussion symptoms. Parents and coaches need to weigh the benefits of
      participation with the frequency of injuries, missed academic time, and the cost
      of medical treatment.

PMID- 29473833
TI  - Internal Fixation of Osteoporotic Bone.
AB  - Osteoporosis is one of the costliest conditions managed by orthopaedic surgeons.
      This condition, which is characterized by decreased bone density and thinning of
      cortical bone, is strongly influenced by complex signaling in both the hormonal
      and mechanical environments. Osteoporosis cannot be cured; instead, it can only
      be managed to decrease patient morbidity. Current pharmacologic treatments are
      aimed at minimizing bone turnover and have substantial side effects. Therefore,
      much work remains to find safer and more effective agents to restore bone
      density. In addition to the high incidence of fracture in elderly patients, many
      of the traditional fixation constructs used for repair of these fractures are not
      suitable for use in osteoporotic bone. Increased use of fixed-angle locking
      plates, intramedullary devices, and bone substitutes has greatly improved
      outcomes in these patients.

PMID- 29473834
TI  - Ibrutinib-Induced Neutrophilic Dermatosis.
AB  - We report the case of a 64-year-old woman treated with ibrutinib for a chronic
      lymphocytic leukemia with 17p deletion, who developed several erythematous,
      painful, and papulo-nodular skin lesions in the limbs, neck, and face. The skin
      biopsy was consistent with the diagnosis of neutrophilic dermatosis. Rechallenge
      with ibrutinib at full dose was followed by the recurrence of the same skin
      lesions, strongly suggesting a direct relationship.

PMID- 29473835
TI  - Hydroa Vacciniforme-Like Cutaneous T-Cell Lymphoma in an Adult Presenting With
      Facial Edema and Recurrent Oral Ulceration.

PMID- 29473836
TI  - Pruriginous Lesions in a Young Girl: Challenge.

PMID- 29473837
TI  - Graduate Medical Education Funding and Curriculum in Physical Medicine and
      Rehabilitation: A Survey of Physical Medicine and Rehabilitation Department
      Chairs.
AB  - This national survey highlights graduate medical education funding sources for
      physical medicine and rehabilitation (PM&R) residency programs as well as
      perceived funding stability, alignment of the current funding and educational
      model, the need of further education in postacute care settings, and the practice
      of contemporary PM&R graduates as perceived by PM&R department/division chairs.
      Approximately half of the reported PM&R residency positions seem to be funded by
      Centers of Medicare and Medicaid Services; more than 40% of PM&R chairs believe
      that their residency program is undersized and nearly a quarter feel at risk for
      losing positions. A total of 30% of respondents report PM&R resident experiences
      in home health, 15% in long-term acute care, and 52.5% in a skilled nursing
      facility/subacute rehabilitation facility. In programs that do not offer these
      experiences, most chairs feel that this training should be included. In addition,
      study results suggest that most PM&R graduates work in an outpatient setting.
      Based on the results that chairs strongly feel the need for resident education in
      postacute care settings and that most graduates go on to practice in outpatient
      settings, there is a potential discordance for our current Centers of Medicare
      and Medicaid Services graduate medical education funding model being linked to
      the acute care setting.

PMID- 29473838
TI  - "Nano-Ginseng" for Enhanced Cytotoxicity AGAINST Cancer Cells.
AB  - Panax ginseng has high medicinal and health values. However, the various and
      complex components of ginseng may interact with each other, thus reducing and
      even reversing therapeutic effects. In this study, we designed and fabricated a
      novel "nano-ginseng" with definite ingredients, ginsenoside Rb1/protopanaxadiol
      nanoparticles (Rb1/PPD NPs), completely based on the protopanaxadiol-type
      extracts. The optimized nano-formulations demonstrated an appropriate size (~110
      nm), high drug loading efficiency (~96.8%) and capacity (~27.9 wt %), long half
      time in systemic circulation (nine-fold longer than free PPD), better antitumor
      effects in vitro and in vivo, higher accumulation at the tumor site and reduced
      damage to normal tissues. Importantly, this process of "nano-ginseng" production
      is a simple, scalable, green economy process.

PMID- 29473839
TI  - Sulphated Flavonoids: Biosynthesis, Structures, and Biological Activities.
AB  - The great diversity of enzymatic reactions in plant secondary metabolism allows
      the continuous discovery of new natural compounds and derivatives. Flavonoids,
      for example, can be found as aglycone or as several sorts of glycosylated,
      acetylated, methylated, and sulphated derivatives. This review focuses on
      sulphated flavonoids, an uncommon group of flavonoid derivatives found in some
      plant families. This work presents a compilation of sulphated flavonoids and
      their natural sources reported in the literature. Biosynthetic aspects and
      biological activities have also been reviewed, showing that these particular
      kinds of natural compounds play an interesting role in plant metabolism, as well
      as being potential candidates for the development of new drugs.

PMID- 29473840
TI  - Adaptive Correlation Model for Visual Tracking Using Keypoints Matching and Deep
      Convolutional Feature.
AB  - Although correlation filter (CF)-based visual tracking algorithms have achieved
      appealing results, there are still some problems to be solved. When the target
      object goes through long-term occlusions or scale variation, the correlation
      model used in existing CF-based algorithms will inevitably learn some non-target
      information or partial-target information. In order to avoid model contamination
      and enhance the adaptability of model updating, we introduce the keypoints
      matching strategy and adjust the model learning rate dynamically according to the
      matching score. Moreover, the proposed approach extracts convolutional features
      from a deep convolutional neural network (DCNN) to accurately estimate the
      position and scale of the target. Experimental results demonstrate that the
      proposed tracker has achieved satisfactory performance in a wide range of
      challenging tracking scenarios.

PMID- 29473842
TI  - Antioxidant Activity and Protective Effects of Enzyme-Extracted Oudemansiella
      radiata Polysaccharides on Alcohol-Induced Liver Injury.
AB  - This work was to examine the antioxidation in vitro and hepatoprotective effects
      of enzyme-extracted Oudemansiella radiata polysaccharides (En-OPS) on alcohol
      induced liver damage in mice. The antioxidant activities were determined
      according to the scavenging effects of En-OPS on hydroxyl, superoxide, and 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radicals, and the level of reducing power. En
      OPS showed hepatoprotective activities on decreasing the serum levels of
      aspertate aminotransferase (AST), alamine aminotransferase (ALT), and alkaline
      phosphatase (ALP), as well as hepatic lipid levels of total cholesterol (TC) and
      triacylglycerols (TG). En-OPS treatment reversed the acute impairment induced by
      alcohol consumption, including reactive oxygen species (ROS) generation,
      malondialdehyde (MAD), and lipid peroxide (LPO) elevation; and superoxide
      dismutase (SOD), GSH peroxide (GSH-Px), catalase (CAT), and total antioxidant
      capacity (T-AOC) impairment. The En-OPS effectively ameliorated alcohol
      metabolism by activating alcohol dehydrogenase (ADH) and aldehyde dehydrogenase
      (ALDH), and reducing cytochrome P450 2E1 (CYP2E1) levels. Furthermore, the
      histopathological observations also displayed that En-OPS could alleviate liver
      damage. These results indicated that En-OPS could be suitable to be an ingredient
      of preventing alcoholic liver diseases (ALD). In addition, the preliminary
      structure characteristics of En-OPS were also analyzed by Fourier transform
      infrared (FT-IR) spectroscopy and a gas chromatography-flame ionization detector
      (GC-FID).

PMID- 29473841
TI  - Bioenergetics of Mycobacterium: An Emerging Landscape for Drug Discovery.
AB  - Mycobacterium tuberculosis (Mtb) exhibits remarkable metabolic flexibility that
      enables it to survive a plethora of host environments during its life cycle. With
      the advent of bedaquiline for treatment of multidrug-resistant tuberculosis,
      oxidative phosphorylation has been validated as an important target and a
      vulnerable component of mycobacterial metabolism. Exploiting the dependence of
      Mtb on oxidative phosphorylation for energy production, several components of
      this pathway have been targeted for the development of new antimycobacterial
      agents. This includes targeting NADH dehydrogenase by phenothiazine derivatives,
      menaquinone biosynthesis by DG70 and other compounds, terminal oxidase by
      imidazopyridine amides and ATP synthase by diarylquinolines. Importantly,
      oxidative phosphorylation also plays a critical role in the survival of
      persisters. Thus, inhibitors of oxidative phosphorylation can synergize with
      frontline TB drugs to shorten the course of treatment. In this review, we discuss
      the oxidative phosphorylation pathway and development of its inhibitors in
      detail.

PMID- 29473843
TI  - Prevalence of Oral Clefts among Live Births in Gansu Province, China.
AB  - Background: Oral clefts (OCs) are common human birth defects. Children with OCs
      in underdeveloped regions are more likely to suffer from poverty and hardship in
      their future lives. Here, we attempted to estimate the prevalence of OCs among
      live births in Gansu Province in 2008 to understand the epidemiologic pattern of
      the disease. Methods: A cross-sectional study was conducted from January 2008 to
      December 2008 in Gansu Province. The live births delivered between January and
      December 2008 with OCs were investigated through face-to-face questionnaire
      survey. Results: A total of 468 infants with OCs were identified among 347,137
      live births in 2008 in Gansu Province, which yielded a prevalence of 1.35 per
      1000 live births. The majority of these cases were CL (cleft lip) (prevalence =
      0.85 per 1000 live births), and the prevalence of CLP (cleft lip and palate) and
      CP (cleft palate) was 0.34 and 0.11 per 1000 live births, respectively. We also
      found that the prevalence of OCs in Jiayuguan (3.39 per 1000 live births) and
      Dingxi (2.71 per 1000 live births) was higher than those of other cities in Gansu
      Province. Additionally, we failed to detect significant correlation between
      economic conditions of the cities and the prevalence of OCs in our study.
      Conclusions: The prevalence of OCs among live births in Gansu Province in 2008
      was higher than the prevalence of OCs in other provinces in China. The high
      prevalence may reflect the need for further etiological studies to explore the
      potential risk factors in this region. In addition, more subtype information
      needs to be collected in future prevalence studies for better understanding of
      the epidemiologic pattern of the disease.

PMID- 29473844
TI  - Antimicrobial and Antibiofilm Activity and Machine Learning Classification
      Analysis of Essential Oils from Different Mediterranean Plants against
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a ubiquitous organism and opportunistic pathogen that
      can cause persistent infections due to its peculiar antibiotic resistance
      mechanisms and to its ability to adhere and form biofilm. The interest in the
      development of new approaches for the prevention and treatment of biofilm
      formation has recently increased. The aim of this study was to seek new non
      biocidal agents able to inhibit biofilm formation, in order to counteract
      virulence rather than bacterial growth and avoid the selection of escape mutants.
      Herein, different essential oils extracted from Mediterranean plants were
      analyzed for their activity against P. aeruginosa. Results show that they were
      able to destabilize biofilm at very low concentration without impairing bacterial
      viability. Since the action is not related to a bacteriostatic/bactericidal
      activity on P. aeruginosa, the biofilm change of growth in presence of the
      essential oils was possibly due to a modulation of the phenotype. To this aim,
      application of machine learning algorithms led to the development of quantitative
      activity-composition relationships classification models that allowed to direct
      point out those essential oil chemical components more involved in the inhibition
      of biofilm production. The action of selected essential oils on sessile phenotype
      make them particularly interesting for possible applications such as prevention
      of bacterial contamination in the community and in healthcare environments in
      order to prevent human infections. We assayed 89 samples of different essential
      oils as P. aeruginosa anti-biofilm. Many samples inhibited P. aeruginosa biofilm
      at concentrations as low as 48.8 ug/mL. Classification of the models was
      developed through machine learning algorithms.

PMID- 29473845
TI  - Persicaline, A New Antioxidant Sulphur-Containing Imidazoline Alkaloid from
      Salvadora persica Roots.
AB  - Salvadora persica L. is a popular chewing stick commonly known as "miswak".
      During our ongoing research activities on the chemical constituents of Salvadora
      persica roots, which is a new sulphur-containing imidazoline alkaloid 1,3
      Dibenzyl-4-(1,2,3,4-tetrahydroxy-butyl)-1,3-dihydro-imidazole-2-thione,
      persicaline, (1) along with five known compounds (2-6) are identified. Compounds
      (2, 3) were reported for the first time from the family Salvadoraeceae. The
      structure of the new compound was established by extensive spectroscopic data and
      HR-MS. The antioxidant activities of the fractions and isolates were evaluated
      using different in vitro methods, such as DPPH, superoxide anion and nitric oxide
      radicals scavenging assays. Compound (1) showed a promising antioxidant activity
      with IC50 0.1, 0.08, and 0.09 uM in the three assays, respectively, comparable to
      ascorbic acid.

PMID- 29473846
TI  - Epigallocatechin Gallate Reduces Ischemia/Reperfusion Injury in Isolated Perfused
      Rabbit Hearts.
AB  - Cardioplegic arrest during heart operations is often used in cardiac surgery.
      During cardioplegia, the heart is subjected to a global ischemia/reperfusion
      injury. (-)-epigallocatechin gallate (EGCG), one of the main ingredients of green
      tea, seems to be beneficial in various cardiac diseases. Therefore, the aim of
      our study was to evaluate EGCG in a rabbit model of cardioplegic arrest. Twenty
      four mature Chinchilla rabbits were examined. Rabbit hearts were isolated and
      perfused according to Langendorff. After induction of cardioplegia (without and
      with 20 umol/L EGCG, n = 6 each) the hearts maintained arrested for 90-min.
      Thereafter, the hearts were re-perfused for 60 min. During the entire experiment
      hemodynamic and functional data were assessed. At the end of each experiment,
      left ventricular samples were processed for ATP measurements and for histological
      analysis. Directly after cessation of cardioplegia, all hearts showed the same
      decline in systolic and diastolic function. However, hearts of the EGCG-group
      showed a significantly faster and better hemodynamic recovery during reperfusion.
      In addition, tissue ATP-levels were significantly higher in the EGCG-treated
      hearts. Histological analysis revealed that markers of nitrosative and oxidative
      stress were significantly lower in the EGCG group. Thus, addition of EGCG
      significantly protected the cardiac muscle from ischemia/reperfusion injury.

PMID- 29473847
TI  - Impact of Storage Conditions on the Stability of Predominant Phenolic
      Constituents and Antioxidant Activity of Dried Piper betle Extracts.
AB  - The phenolic constituents in Piper betle are well known for their antioxidant
      potential; however, current literature has very little information on their
      stability under the influence of storage factors. Present study evaluated the
      stability of total phenolic content (TPC) and antioxidant activity together with
      individual phenolic constituents (hydroxychavicol, eugenol, isoeugenol and
      allylpyrocatechol 3,4-diacetate) present in dried Piper betle's extract under
      different storage temperature of 5 and 25  degrees C with and without light for a
      period of six months. Both light and temperature significantly influenced TPC and
      its corresponding antioxidant activity over time. More than 95% TPC and
      antioxidant activity was retained at 5  degrees C in dark condition after 180
      days of storage. Hydroxychavicol demonstrated the best stability with no
      degradation while eugenol and isoeugenol displayed moderate stability in low
      temperature (5  degrees C) and dark conditions. 4-allyl-1,2-diacetoxybenzene was
      the only compound that underwent complete degradation. A new compound, 2,4-di
      tert-butylphenol, was detected after five weeks of storage only in the extracts
      exposed to light. Both zero-order and first-order kinetic models were adopted to
      describe the degradation kinetics of the extract's antioxidant activity. Zero
      order displayed better fit with higher correlation coefficients (R2 = 0.9046) and
      the half-life was determined as 62 days for the optimised storage conditions (5 
      degrees C in dark conditions).

PMID- 29473848
TI  - Bovine alpha-Lactalbumin Hydrolysates (alpha-LAH) Ameliorate Adipose Insulin
      Resistance and Inflammation in High-Fat Diet-Fed C57BL/6J Mice.
AB  - Obesity-induced adipose inflammation has been demonstrated to be a key cause of
      insulin resistance. Peptides derived from bovine alpha-lactalbumin have been
      shown to inhibit the activities of dipeptidyl peptidase IV (DPP-IV) and
      angiotensin converting enzyme (ACE), scavenge 2,2'-azinobis [3
      ethylbenzothiazoline-6-sulfonate] (ABTS+) radical and stimulate glucagon-like
      peptide-2 secretion. In the present study, the effects of bovine alpha
      lactalbumin hydrolysates (alpha-LAH) on adipose insulin resistance and
      inflammation induced by high-fat diet (HFD) were investigated. The insulin
      resistance model was established by feeding C57BL/6J mice with HFD (60% kcal from
      fat) for eight weeks. Then, the mice were fed with HFD and bovine alpha-LAH of
      different doses (100 mg/kg b.w., 200 mg/kg b.w. and 400 mg/kg b.w.) for another
      12 weeks to evaluate its protective effects against HFD-induced insulin
      resistance. The oral glucose tolerance test (OGTT) and intraperitoneal insulin
      tolerance test (ipITT) were conducted after intervention with alpha-LAH for 10
      weeks and 11 weeks, respectively. Results showed that bovine alpha-LAH
      significantly reduced body weight, blood glucose, serum insulin, and HOMA-IR
      (homeostatic model assessment of insulin resistance) levels, lowered the area
      under-the-curve (AUC) during OGTT and ipITT, and downregulated inflammation
      related gene [tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, monocyte
      chemoattractant protein (MCP)-1] expression in adipose tissues of HFD-fed
      C57BL/6J mice. Furthermore, bovine alpha-LAH also suppressed insulin receptor
      substrate 1 (IRS-1) serine phosphorylation (Ser307, Ser612), enhanced protein
      kinase B (known as Akt) phosphorylation, and inhibited the activation of
      inhibitor of kappaB kinase (IKK) and mitogen activated protein kinase (MAPK)
      signaling pathways in adipose tissues of HFD-fed C57BL/6J mice. These results
      suggested that bovine alpha-LAH could ameliorate adipose insulin resistance and
      inflammation through IKK and MAPK signaling pathways in HFD-fed C57BL/6J mice.

PMID- 29473849
TI  - Epitaxially Grown Ultra-Flat Self-Assembling Monolayers with Dendrimers.
AB  - Mono-molecular films formed by physical adsorption and dendrimer self-assembly
      were prepared on various substrate surfaces. It was demonstrated that a uniform
      dendrimer-based monolayer on the subnanometer scale can be easily constructed via
      simple dip coating. Furthermore, it was shown that an epitaxially grown monolayer
      film reflecting the crystal structure of the substrate (highly ordered pyrolytic
      graphite (HOPG)) can also be formed by aligning specific conditions.

PMID- 29473850
TI  - Reconstructing Phylogeny by Aligning Multiple Metabolic Pathways Using Functional
      Module Mapping.
AB  - Comparison of metabolic pathways provides a systematic way for understanding the
      evolutionary and phylogenetic relationships in systems biology. Although a number
      of phylogenetic methods have been developed, few efforts have been made to
      provide a unified phylogenetic framework that sufficiently reflects the metabolic
      features of organisms. In this paper, we propose a phylogenetic framework that
      characterizes the metabolic features of organisms by aligning multiple metabolic
      pathways using functional module mapping. Our method transforms the alignment of
      multiple metabolic pathways into constructing the union graph of pathways, builds
      mappings between functional modules of pathways in the union graph, and infers
      phylogenetic relationships among organisms based on module mappings. Experimental
      results show that the use of functional module mapping enables us to correctly
      categorize organisms into main categories with specific metabolic
      characteristics. Traditional genome-based phylogenetic methods can reconstruct
      phylogenetic relationships, whereas our method can offer in-depth metabolic
      analysis for phylogenetic reconstruction, which can add insights into traditional
      phyletic reconstruction. The results also demonstrate that our phylogenetic trees
      are closer to the classic classifications in comparison to existing
      classification methods using metabolic pathway data.

PMID- 29473851
TI  - Fast and Simple Analytical Method for Direct Determination of Total Chlorine
      Content in Polyglycerol by ICP-MS.
AB  - The fast and simple method for total chlorine determination in polyglycerols
      using low resolution inductively coupled plasma mass spectrometry (ICP-MS)
      without the need for additional equipment and time-consuming sample decomposition
      was evaluated. Linear calibration curve for 35Cl isotope in the concentration
      range 20-800 ug/L was observed. Limits of detection and quantification equaled to
      15 ug/L and 44 ug/L, respectively. This corresponds to possibility of detection 3
      ug/g and determination 9 ug/g of chlorine in polyglycerol using studied
      conditions (0.5% matrix-polyglycerol samples diluted or dissolved with water to
      an overall concentration of 0.5%). Matrix effects as well as the effect of
      chlorine origin have been evaluated. The presence of 0.5% (m/m) of matrix species
      similar to polyglycerol (polyethylene glycol-PEG) did not influence the chlorine
      determination for PEGs with average molecular weights (MW) up to 2000 Da. Good
      precision and accuracy of the chlorine content determination was achieved
      regardless on its origin (inorganic/organic). High analyte recovery level and low
      relative standard deviation values were observed for real polyglycerol samples
      spiked with chloride. Additionally, the Combustion Ion Chromatography System was
      used as a reference method. The results confirmed high accuracy and precision of
      the tested method.

PMID- 29473852
TI  - An Interaction of Rhamnolipids with Cu2+ Ions.
AB  - This study was focused on the description of interaction between Cu2+ ions and
      the 1:1 mono- and dirhamnolipid mixtures in the premicellar and aggregated state
      in water and 20 mM KCl solution at pH 5.5 and 6.0. The critical micelle
      concentration of biosurfactants was determined conductometrically and by the pH
      measurements. Hydrodynamic diameter and electrophoretic mobility were determined
      in micellar solutions using dynamic light scattering and laser Doppler
      electrophoresis, respectively. The copper immobilization by rhamnolipids,
      methylglycinediacetic acid (MGDA), and ethylenediaminetetraacetic acid (EDTA) was
      estimated potentiometrically for the Cu2+ to chelating agent molar ratio from
      16:100 to 200:100. The degree of ion binding and the complex stability constant
      were calculated at a 1:1 metal to chelant molar ratio. The aggregates of
      rhamnolipids (diameter of 43-89 nm) were negatively charged. Biosurfactants
      revealed the best chelating activities in premicellar solutions. For all chelants
      studied the degree of metal binding decreased with the increasing concentration
      of the systems. The presence of K+ lowered Cu2+ binding by rhamnolipids, but did
      not modify the complex stability significantly. Immobilization of Cu2+ by
      biosurfactants did not cause such an increase of acidification as that observed
      in MGDA and EDTA solutions. Rhamnolipids, even in the aggregated form, can be an
      alternative for the classic chelating agents.

PMID- 29473854
TI  - Dynamic Diffraction Studies on the Crystallization, Phase Transformation, and
      Activation Energies in Anodized Titania Nanotubes.
AB  - The influence of calcination time on the phase transformation and crystallization
      kinetics of anodized titania nanotube arrays was studied using in-situ isothermal
      and non-isothermal synchrotron radiation diffraction from room temperature to 900
      degrees C. Anatase first crystallized at 400  degrees C, while rutile
      crystallized at 550  degrees C. Isothermal heating of the anodized titania
      nanotubes by an increase in the calcination time at 400, 450, 500, 550, 600, and
      650  degrees C resulted in a slight reduction in anatase abundance, but an
      increase in the abundance of rutile because of an anatase-to-rutile
      transformation. The Avrami equation was used to model the titania crystallization
      mechanism and the Arrhenius equation was used to estimate the activation energies
      of the titania phase transformation. Activation energies of 22 (10) kJ/mol for
      the titanium-to-anatase transformation, and 207 (17) kJ/mol for the anatase-to
      rutile transformation were estimated.

PMID- 29473853
TI  - Antioxidant Tocols as Radiation Countermeasures (Challenges to be Addressed to
      Use Tocols as Radiation Countermeasures in Humans).
AB  - Radiation countermeasures fall under three categories, radiation protectors,
      radiation mitigators, and radiation therapeutics. Radiation protectors are agents
      that are administered before radiation exposure to protect from radiation-induced
      injuries by numerous mechanisms, including scavenging free radicals that are
      generated by initial radiochemical events. Radiation mitigators are agents that
      are administered after the exposure of radiation but before the onset of symptoms
      by accelerating the recovery and repair from radiation-induced injuries. Whereas
      radiation therapeutic agents administered after the onset of symptoms act by
      regenerating the tissues that are injured by radiation. Vitamin E is an
      antioxidant that neutralizes free radicals generated by radiation exposure by
      donating H atoms. The vitamin E family consists of eight different vitamers,
      including four tocopherols and four tocotrienols. Though alpha-tocopherol was
      extensively studied in the past, tocotrienols have recently gained attention as
      radiation countermeasures. Despite several studies performed on tocotrienols,
      there is no clear evidence on the factors that are responsible for their superior
      radiation protection properties over tocopherols. Their absorption and
      bioavailability are also not well understood. In this review, we discuss
      tocopherol's and tocotrienol's efficacy as radiation countermeasures and identify
      the challenges to be addressed to develop them into radiation countermeasures for
      human use in the event of radiological emergencies.

PMID- 29473855
TI  - Children's Environmental Health in the Digital Era: Understanding Early Screen
      Exposure as a Preventable Risk Factor for Obesity and Sleep Disorders.
AB  - The quantity, accessibility and focus on child-targeted programming has
      exponentially increased since it entered American households in the early 1900s.
      It may have started with the television (TV), but technology has evolved and now
      fits in our pockets; as of 2017, 95% of American families own a smartphone.
      Availability and child-tailored content has subsequently led to a decrease in the
      age at initial screen exposure. The negative effects that accompany the current
      culture of early screen exposure are extensive and need to be considered as
      technology continues to enter the home and inundate social interactions.
      Increased levels of early screen exposure have been associated with decreased
      cognitive abilities, decreased growth, addictive behavior, poor school
      performance, poor sleep patterns, and increased levels of obesity. Research on
      the adverse effects of early screen exposure is mounting, but further
      epidemiological studies are still needed to inform prevention and regulation
      policies.

PMID- 29473856
TI  - Fast Determination of Yttrium and Rare Earth Elements in Seawater by Inductively
      Coupled Plasma-Mass Spectrometry after Online Flow Injection Pretreatment.
AB  - A method for daily monitoring of yttrium and rare earth elements (YREEs) in
      seawater using a cheap flow injection system online coupled to inductively
      coupled plasma-mass spectrometry is reported. Toyopearl AF Chelate 650M(r) resin
      permits separation and concentration of YREEs using a simple external
      calibration. A running cycle consumed 6 mL sample and took 5.3 min, providing a
      throughput of 11 samples per hour. Linear ranges were up to 200 ng kg-1 except Tm
      (100 ng kg-1). The precision of the method was <6% (RSDs, n = 5), and recoveries
      ranged from 93% to 106%. Limits of detection (LODs) were in the range 0.002 ng kg
      1 (Tm) to 0.078 ng kg-1 (Ce). Good agreement between YREEs concentrations in CASS
      4 and SLEW-3 obtained in this work and results from other studies was observed.
      The proposed method was applied to the determination of YREEs in seawater from
      the Jiulong River Estuary and the Taiwan Strait.

PMID- 29473857
TI  - Structural Dynamics of DPP-4 and Its Influence on the Projection of Bioactive
      Ligands.
AB  - Dipeptidyl peptidase-4 (DPP-4) is a target to treat type II diabetes mellitus.
      Therefore, it is important to understand the structural aspects of this enzyme
      and its interaction with drug candidates. This study involved molecular dynamics
      simulations, normal mode analysis, binding site detection and analysis of
      molecular interactions to understand the protein dynamics. We identified some DPP
      4 functional motions contributing to the exposure of the binding sites and twist
      movements revealing how the two enzyme chains are interconnected in their
      bioactive form, which are defined as chains A (residues 40-767) and B (residues
      40-767). By understanding the enzyme structure, its motions and the regions of
      its binding sites, it will be possible to contribute to the design of new DPP-4
      inhibitors as drug candidates to treat diabetes.

PMID- 29473859
TI  - Impact on Clinical Management of After-Hours Emergent or Urgent Breast
      Ultrasonography in Patients with Clinically Suspected Breast Abscesses.
AB  - Newly diagnosed breast abscesses are generally treated as a medical emergency
      that may necessitate immediate interventional treatment. At our institution,
      there is no in-house after-hours coverage for breast ultrasonography. We could
      find no peer-reviewed studies on the cost-effectiveness or clinical management
      impact of on-call ultrasound technologist coverage for imaging of breast
      abscesses. The purposes of this study were to determine the incidence of breast
      abscess in patients with clinical findings highly suggestive of abscess, identify
      clinical factors associated with breast abscess in such patients, and determine
      the impact of after-hours emergent or urgent breast ultrasonography on the
      clinical management of breast abscesses in both outpatients and inpatients. We
      retrospectively reviewed 100 after-hours breast ultrasound studies performed at
      our tertiary care center from 2011 to 2015 for evaluation of a suspected breast
      abscess. Only 26% of our patients with clinically suspected abscess ultimately
      had a confirmed abscess. Factors associated with breast abscess were a palpable
      abnormality and a history of breast surgery within the eight weeks before
      presentation. After-hours diagnosis of an abscess was associated with after-hours
      clinical intervention. Of the 74 patients in whom after-hours ultrasound imaging
      showed no evidence of abscess, only three patients underwent after-hours
      drainage. Our findings support overnight and weekend breast ultrasound coverage
      in large tertiary care centers.

PMID- 29473860
TI  - Carcinoembryonic Antigen Serum Levels in Nonmelanoma Skin Cancer.
AB  - BACKGROUND: Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in
      the foetal colon, some benign conditions and different malignancies, particularly
      in colon adenocarcinoma. We focused this study on non-melanoma skin cancer
      (NMSC). NMSC is a common malignancy and it is an important source of morbidity
      and death in the world. In this study we evaluated whether CEA level increases in
      NMSC. PATIENTS AND METHODS: A total of 566 patients with non-melanoma skin cancer
      (NMSC) were enrolled; 286 patients with NMSC showed CEA levels above normal
      values, and 280 showed CEA levels below normal values. Patients with high levels
      of CEA underwent abdominal ultrasound, gastro endoscopy, colonoscopy, and
      abdominal CT scans. RESULTS: We studied 566 patients, 286 were positive to CEA
      and 280 were negative. Of the 286 patients positive to CEA, 132 had basal cell
      carcinoma (64 patients had an associated cancer) and 154 had squamous cell
      carcinoma (75 patients were affected by cancer). Of the 280 patients negative to
      CEA, 130 had basal cell carcinoma (12 were associated with cancer), and 150 had
      squamous cell carcinoma (18 were associated with cancer). The mean age of the 566
      case control subjects were 65-81 years. Of the 10 subjects that were the positive
      control for CEA, two had cancer. Of the 556 subjects that were the negative
      control for CEA, three had cancer. CONCLUSIONS: In patients that present high
      serum levels of CEA, we give attention to adenocarcinoma tumour first. The
      pattern of association may be attributable to bias because the group with NMSC
      were frequently evaluated than those with no history of NMSC. Our results showed
      that out of 286 patients that were CEA-positive, 139 had cancer, and of the 280
      that were CEA-negative, 30 had cancer. Therefore, 20% of patients do not follow
      the trend. Other markers should be investigated.

PMID- 29473858
TI  - Indispensable Role of Proteases in Plant Innate Immunity.
AB  - Plant defense is achieved mainly through the induction of microbe-associated
      molecular patterns (MAMP)-triggered immunity (MTI), effector-triggered immunity
      (ETI), systemic acquired resistance (SAR), induced systemic resistance (ISR), and
      RNA silencing. Plant immunity is a highly complex phenomenon with its own unique
      features that have emerged as a result of the arms race between plants and
      pathogens. However, the regulation of these processes is the same for all living
      organisms, including plants, and is controlled by proteases. Different families
      of plant proteases are involved in every type of immunity: some of the proteases
      that are covered in this review participate in MTI, affecting stomatal closure
      and callose deposition. A large number of proteases act in the apoplast,
      contributing to ETI by managing extracellular defense. A vast majority of the
      endogenous proteases discussed in this review are associated with the programmed
      cell death (PCD) of the infected cells and exhibit caspase-like activities. The
      synthesis of signal molecules, such as salicylic acid, jasmonic acid, and
      ethylene, and their signaling pathways, are regulated by endogenous proteases
      that affect the induction of pathogenesis-related genes and SAR or ISR
      establishment. A number of proteases are associated with herbivore defense. In
      this review, we summarize the data concerning identified plant endogenous
      proteases, their effect on plant-pathogen interactions, their subcellular
      localization, and their functional properties, if available, and we attribute a
      role in the different types and stages of innate immunity for each of the
      proteases covered.

PMID- 29473861
TI  - Nutrient Limitation Inactivates Mrc1-to-Cds1 Checkpoint Signalling in
      Schizosaccharomyces pombe.
AB  - The S. pombe checkpoint kinase, Cds1, protects the integrity of stalled DNA
      replication forks after its phosphorylation at threonine-11 by Rad3 (ATR).
      Modified Cds1 associates through its N-terminal forkhead-associated domain (FHA)
      domain with Mrc1 (Claspin) at stalled forks. We report here that nutrient
      starvation results in post-translational changes to Cds1 and the loss of Mrc1. A
      drop in glucose after a down-shift from 3% to 0.1-0.3%, or when cells enter the
      stationary phase, triggers a sharp decline in Mrc1 and the accumulation of
      insoluble Cds1. Before this transition, Cds1 is transiently activated and
      phosphorylated by Rad3 when glucose levels fall. Because this coincides with the
      phosphorylation of histone 2AX at S129 by Rad3, an event that occurs towards the
      end of every unperturbed S phase, we suggest that a glucose limitation promotes
      the exit from the S phase. Since nitrogen starvation also depletes Mrc1 while
      Cds1 is post-translationally modified, we suggest that nutrient limitation is the
      general signal that promotes exit from S phase before it inactivates the Mrc1
      Cds1 signalling component. Why Cds1 accumulates in resting cells while its
      activator Mrc1 declines is, as yet, unclear but suggests a novel function of Cds1
      in non-replicating cells.

PMID- 29473862
TI  - Using a Second Order Sigma-Delta Control to Improve the Performance of Metal
      Oxide Gas Sensors.
AB  - Controls of surface potential have been proposed to accelerate the time response
      of MOX gas sensors. These controls use temperature modulations and a feedback
      loop based on first-order sigma-delta modulators to keep constant the surface
      potential. Changes in the surrounding gases, therefore, must be compensated by
      average temperature produced by the control loop, which is the new output signal.
      The purpose of this paper is to present a second order sigma-delta control of the
      surface potential for gas sensors. With this new control strategy, it is possible
      to obtain a second order zero of the quantization noise in the output signal.
      This provides a less noisy control of the surface potential, while at the same
      time some undesired effects of first order modulators, such as the presence of
      plateaus, are avoided. Experiments proving these performance improvements are
      presented using a gas sensor made of tungsten oxide nanowires. Plateau avoidance
      and second order noise shaping is shown with ethanol measurements.

PMID- 29473863
TI  - Applicability of the Nordic Occupational Skin Questionnaire for Screening Contact
      Dermatological Disorders in Sea Fishers.
AB  - This survey aimed to evaluate the applicability of the Nordic Occupational Skin
      Questionnaire (NOSQ) as a preliminary screening tool to investigate the presence
      of contact dermatological disorders in sea fishermen. The Italian version of the
      NOSQ was administered to 143 male fishermen working at an Apulia (Southern Italy)
      Fisheries, and 136 male workers who had never worked as sea fishers (controls). A
      significantly higher rate of frequency of transient itchy wheals on the hands,
      wrists, and forearms was recorded in the fishermen as compared to the controls
      (49.6% vs. 8.1%; p < 0.001), while there was no significant difference in the
      frequency of eczema (8.4% vs. 6.6%). In 46.1% of the fishermen, the onset of
      transient itchy wheals was associated with contact with specific agents and the
      most common causes were algae and aquatic plants (49.3%) and seabed sludge
      (25.3%). In conclusion, the administration of the NOSQ can be useful in
      preliminary screening for dermatitis in fishermen, although it could show a
      possible overestimation of the prevalence of transient itchy wheals.

PMID- 29473865
TI  - Bottom-Up Electrodeposition of Large-Scale Nanotwinned Copper within 3D Through
      Silicon Via.
AB  - This paper is the first to report a large-scale directcurrent electrodeposition
      of columnar nanotwinned copper within through silicon via (TSV) with a high
      aspect ratio (~4). With this newly developed technique, void-free nanotwinned
      copper array could be fabricated in low current density (30 mA/cm2) and
      convection conditions (300 rpm), which are the preconditions for copper
      deposition with a uniform deep-hole microstructure. The microstructure of a whole
      cross-section of deposited copper array was made up of (111) orientated columnar
      grains with parallel nanoscale twins that had thicknesses of about 22 nm. The
      hardness was also uniform along the growth direction, with 2.34 and 2.68 GPa for
      the top and bottom of the TSV, respectively. The gelatin additive is also first
      reported hereas a key factor in forming nanoscale twins by adsorbing on the
      cathode surface, in order to enhance the overpotential for cathodic reaction
      during the copper deposition process.

PMID- 29473864
TI  - Triterpenoid Saponins from Anemone rivularis var. Flore-Minore and Their Anti
      Proliferative Activity on HSC-T6 Cells.
AB  - Five previously undescribed triterpenoid saponins (1-5), along with eight known
      ones (6-13), were isolated from the whole plants of Anemone rivularis var. flore
      minore. Their structures were clarified by extensive spectroscopic data and
      chemical evidence. For the first time, the lupane-type saponins (3 and 12) were
      reported from the Anemone genus. The anti-proliferative activity of all isolated
      saponins was evaluated on hepatic stellate cells (HSC-T6). Saponins 12 and 13,
      which possess more monosaccharides than the others, displayed potent anti
      proliferative activity, with IC50 values of 18.21 and 15.56 MUM, respectively.

PMID- 29473866
TI  - Molecular Modeling Study for the Design of Novel Peroxisome Proliferator
      Activated Receptor Gamma Agonists using 3D-QSAR and Molecular Docking.
AB  - Type 2 diabetes is becoming a global pandemic disease. As an important target for
      the generation and development of diabetes mellitus, peroxisome proliferator
      activated receptor gamma (PPARgamma) has been widely studied. PPARgamma agonists
      have been designed as potential anti-diabetic agents. The advanced development of
      PPARgamma agonists represents a valuable research tool for diabetes therapy. To
      explore the structural requirements of PPARgamma agonists, three-dimensional
      quantitative structure-activity relationship (3D-QSAR) and molecular docking
      studies were performed on a series of N-benzylbenzamide derivatives employing
      comparative molecular field analysis (CoMFA), comparative molecular similarity
      indices analysis (CoMSIA), and surflex-dock techniques. The generated models of
      CoMFA and CoMSIA exhibited a high cross-validation coefficient (q2) of 0.75 and
      0.551, and a non-cross-validation coefficient (r2) of 0.958 and 0.912,
      respectively. The predictive ability of the models was validated using external
      validation with predictive factor (r2pred) of 0.722 and 0.682, respectively.
      These results indicate that the model has high statistical reliability and good
      predictive power. The probable binding modes of the best active compounds with
      PPARgamma active site were analyzed, and the residues His323, Tyr473, Ser289 and
      Ser342 were found to have hydrogen bond interactions. Based on the analysis of
      molecular docking results, and the 3D contour maps generated from CoMFA and
      CoMSIA models, the key structural features of PPARgamma agonists responsible for
      biological activity could be determined, and several new molecules, with
      potentially higher predicted activity, were designed thereafter. This work may
      provide valuable information in further optimization of N-benzylbenzamide
      derivatives as PPARgamma agonists.

PMID- 29473867
TI  - Microwave Sensors for Breast Cancer Detection.
AB  - Breast cancer is the leading cause of death among females, early diagnostic
      methods with suitable treatments improve the 5-year survival rates significantly.
      Microwave breast imaging has been reported as the most potential to become the
      alternative or additional tool to the current gold standard X-ray mammography for
      detecting breast cancer. The microwave breast image quality is affected by the
      microwave sensor, sensor array, the number of sensors in the array and the size
      of the sensor. In fact, microwave sensor array and sensor play an important role
      in the microwave breast imaging system. Numerous microwave biosensors have been
      developed for biomedical applications, with particular focus on breast tumor
      detection. Compared to the conventional medical imaging and biosensor techniques,
      these microwave sensors not only enable better cancer detection and improve the
      image resolution, but also provide attractive features such as label-free
      detection. This paper aims to provide an overview of recent important
      achievements in microwave sensors for biomedical imaging applications, with
      particular focus on breast cancer detection. The electric properties of
      biological tissues at microwave spectrum, microwave imaging approaches, microwave
      biosensors, current challenges and future works are also discussed in the
      manuscript.

PMID- 29473868
TI  - Oncotargeting by Vesicular Stomatitis Virus (VSV): Advances in Cancer Therapy.
AB  - Modern oncotherapy approaches are based on inducing controlled apoptosis in tumor
      cells. Although a number of apoptosis-induction approaches are available, site
      specific delivery of therapeutic agents still remain the biggest hurdle in
      achieving the desired cancer treatment benefit. Additionally, systemic treatment
      induced toxicity remains a major limiting factor in chemotherapy. To specifically
      address drug-accessibility and chemotherapy side effects, oncolytic virotherapy
      (OV) has emerged as a novel cancer treatment alternative. In OV, recombinant
      viruses with higher replication capacity and stronger lytic properties are being
      considered for tumor cell-targeting and subsequent cell lysing. Successful
      application of OVs lies in achieving strict tumor-specific tropism called
      oncotropism, which is contingent upon the biophysical interactions of tumor cell
      surface receptors with viral receptors and subsequent replication of oncolytic
      viruses in cancer cells. In this direction, few viral vector platforms have been
      developed and some of these have entered pre-clinical/clinical trials. Among
      these, the Vesicular stomatitis virus (VSV)-based platform shows high promise, as
      it is not pathogenic to humans. Further, modern molecular biology techniques such
      as reverse genetics tools have favorably advanced this field by creating
      efficient recombinant VSVs for OV; some have entered into clinical trials. In
      this review, we discuss the current status of VSV based oncotherapy, challenges,
      and future perspectives regarding its therapeutic applications in the cancer
      treatment.

PMID- 29473869
TI  - Enantiomeric Mixtures in Natural Product Chemistry: Separation and Absolute
      Configuration Assignment.
AB  - Chiral natural product molecules are generally assumed to be biosynthesized in an
      enantiomerically pure or enriched fashion. Nevertheless, a significant amount of
      racemates or enantiomerically enriched mixtures has been reported from natural
      sources. This number is estimated to be even larger since the enantiomeric purity
      of secondary metabolites is rarely checked in the natural product isolation
      pipeline. This latter fact may have drastic effects on the evaluation of the
      biological activity of chiral natural products. A second bottleneck is the
      determination of their absolute configurations. Despite the widespread use of
      optical rotation and electronic circular dichroism, most of the stereochemical
      assignments are based on empirical correlations with similar compounds reported
      in the literature. As an alternative, the combination of vibrational circular
      dichroism and quantum chemical calculations has emerged as a powerful and
      reliable tool for both conformational and configurational analysis of natural
      products, even for those lacking UV-Vis chromophores. In this review, we aim to
      provide the reader with a critical overview of the occurrence of enantiomeric
      mixtures of secondary metabolites in nature as well the best practices for their
      detection, enantioselective separation using liquid chromatography, and
      determination of absolute configuration by means of vibrational circular
      dichroism and density functional theory calculations.

PMID- 29473870
TI  - Prevalence and Gender-Specific Influencing Factors of Hypertension among Chinese
      Adults: A Cross-Sectional Survey Study in Nanchang, China.
AB  - Hypertension has become the leading cause of death worldwide; data on
      hypertension among Nanchang adults are sparse. The aim of this study was to
      investigate the prevalence and gender-specific influencing factors of
      hypertension in adults in Nanchang, China. A cross-sectional survey was conducted
      with a representative sample of 2722 Chinese residents aged 18 years and above
      between May and September 2016, with a response rate of 92.4% (2516/2722). A
      stratified cluster sampling method was adopted in this study. Data on prevalence
      and influencing factors were obtained from a standard questionnaire and physical
      measurements. Univariate and multivariate logistic regressions were performed to
      analyze the influencing factors. The age-standardized prevalence was 19.8% (18.2
      21.3) (male: 19.5% (18.0-21.1); female, 20.01% (18.5-21.6)). Factors positively
      associated with hypertension prevalence were past smoking, diabetes mellitus
      (DM), and overweight and obesity in both genders. Abdominal obesity and family
      history of cardiovascular diseases (CVD) were risk factors only in males;
      sleeping time and consumption of fresh vegetables and fruits were related to the
      prevalence of hypertension only in females. These findings will form the baseline
      information for the development of more effective approaches to enhance current
      prevention and control management of hypertension.

PMID- 29473872
TI  - Microstructural Evolution of AlCoCrFeNiSi High-Entropy Alloy Powder during
      Mechanical Alloying and Its Coating Performance.
AB  - High-entropy alloys (HEAs) are promising structural materials due to their
      excellent comprehensive performances. The use of mechanically alloyed powders to
      deposit HEA coatings through atmospheric plasma spraying (APS) is an effective
      approach that can broaden the application areas of the HEAs. In this paper, a
      ductility-brittleness AlCoCrFeNiSi system was chosen as an object of study, and
      the detailed evolution of the surface morphology, particle size distribution, and
      microstructure of the powder during mechanical alloying was investigated. An
      AlCoCrFeNiSi HEA coating was deposited using powder milled for 10 h, which can be
      used as an ideal feedstock for APS. The surface morphology, microstructure,
      microhardness, and wear behavior of the coating at room temperature were
      investigated. The results showed that as the milling time increased, the particle
      size first increased, and then decreased. At the milling time of 10 h, simple
      body-centered cubic (BCC) and face-centered cubic (FCC) solid solution phases
      were formed. After spraying, the lamellar structure inside a single particle
      disappeared. An ordered BCC phase was detected, and the diffraction peaks of the
      Si element also disappeared, which indicates that phase transformation occurred
      during plasma spraying. A transmission electron microscopy analysis showed that
      nanometer crystalline grains with a grain size of about 30 nm existed in the APS
      coating. For the coating, an average microhardness of 612 +/- 41 HV was obtained.
      Adhesive wear, tribo-oxidation wear, and slight abrasion wear took place during
      the wear test. The coating showed good wear resistance, with a volume wear rate
      of 0.38 +/- 0.08 * 10-4 mm3.N-1.m-1, which makes it a promising coating for use
      in abrasive environments.

PMID- 29473871
TI  - Impaired Cargo Clearance in the Retinal Pigment Epithelium (RPE) Underlies
      Irreversible Blinding Diseases.
AB  - Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to
      pathological changes in the outer retina. The RPE monolayer, which lies beneath
      the neuroretina, daily internalises and digests large volumes of spent
      photoreceptor outer segments. Impaired cargo handling and processing in the
      endocytic/phagosome and autophagy pathways lead to the accumulation of lipofuscin
      and pyridinium bis-retinoid A2E aggregates and chemically modified compounds such
      as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased
      proteolytic and oxidative stress, resulting in irreversible damage to post
      mitotic RPE cells and development of blinding conditions such as age-related
      macular degeneration, Stargardt disease and choroideremia. Here, we review how
      impaired cargo handling in the RPE results in their dysfunction, discuss new
      findings from our laboratory and consider how newly discovered roles for
      lysosomes and the autophagy pathway could provide insights into retinopathies.
      Studies of these dynamic, molecular events have also been spurred on by recent
      advances in optics and imaging technology. Mechanisms underpinning lysosomal
      impairment in other degenerative conditions including storage disorders, alpha
      synuclein pathologies and Alzheimer's disease are also discussed. Collectively,
      these findings help transcend conventional understanding of these intracellular
      compartments as simple waste disposal bags to bring about a paradigm shift in the
      way lysosomes are perceived.

PMID- 29473873
TI  - New Evidence on the Effect of Medical Insurance on the Obesity Risk of Rural
      Residents: Findings from the China Health and Nutrition Survey (CHNS, 2004-2011).
AB  - The obesity rate in China has risen significantly in the past few decades. While
      a number of causes for the rise in obesity have been explored, little attention
      has been paid to the role of health insurance per se. This study aims to
      investigate the impact of health insurance on the risk of obesity in rural China
      using longitudinal data from the China Health and Nutrition Survey (CHNS). We
      employed pooled ordinary least squares (OLS), probit estimation, and pooled two
      stage least squares (2SLS) for an instrumental variable (IV). The IV model
      revealed that New rural cooperative medical insurance (NRCMS) participation had a
      significant positive impact on people's tendency towards unhealthy lifestyles,
      for instances, high-fat food (8.01% for female and 7.35% for male), cigarette
      smoking (25% for male), heavy drinking (25% for female), sedentary activity (6.48
      h/w for female and 6.48 h/w for male), waist circumference (1.97 cm for female
      and 1.80 cm for male), body mass index (0.58 kg/m2 for female), which in turn
      leads to an elevated probability of general obesity (51% for female) and
      abdominal obesity (24% for female and 20% for male). An "ex ante moral hazard" is
      prevalent in rural China, which should not be ignored by policymakers so as to
      minimize the related low efficiency in the process of promoting the universal
      coverage of insurance.

PMID- 29473874
TI  - Natural Alkaloids and Heterocycles as G-Quadruplex Ligands and Potential
      Anticancer Agents.
AB  - G-quadruplexes are four-stranded nucleic acid secondary structures that are
      formed in guanine-rich sequences. G-quadruplexes are widely distributed in
      functional regions of the human genome and transcriptome, such as human
      telomeres, oncogene promoter regions, replication initiation sites, and
      untranslated regions. Many G-quadruplex-forming sequences are found to be
      associated with cancer, and thus, these non-canonical nucleic acid structures are
      considered to be attractive molecular targets for cancer therapeutics with novel
      mechanisms of action. In this mini review, we summarize recent advances made by
      our lab in the study of G-quadruplex-targeted natural alkaloids and their
      derivatives toward the development of potential anticancer agents.

PMID- 29473875
TI  - Core Sulphate-Reducing Microorganisms in Metal-Removing Semi-Passive Biochemical
      Reactors and the Co-Occurrence of Methanogens.
AB  - Biochemical reactors (BCRs) based on the stimulation of sulphate-reducing
      microorganisms (SRM) are emerging semi-passive remediation technologies for
      treatment of mine-influenced water. Their successful removal of metals and
      sulphate has been proven at the pilot-scale, but little is known about the types
      of SRM that grow in these systems and whether they are diverse or restricted to
      particular phylogenetic or taxonomic groups. A phylogenetic study of four
      established pilot-scale BCRs on three different mine sites compared the diversity
      of SRM growing in them. The mine sites were geographically distant from each
      other, nevertheless the BCRs selected for similar SRM types. Clostridia SRM
      related to Desulfosporosinus spp. known to be tolerant to high concentrations of
      copper were members of the core microbial community. Members of the SRM family
      Desulfobacteraceae were dominant, particularly those related to Desulfatirhabdium
      butyrativorans. Methanogens were dominant archaea and possibly were present at
      higher relative abundances than SRM in some BCRs. Both hydrogenotrophic and
      acetoclastic types were present. There were no strong negative or positive co
      occurrence correlations of methanogen and SRM taxa. Knowing which SRM inhabit
      successfully operating BCRs allows practitioners to target these phylogenetic
      groups when selecting inoculum for future operations.

PMID- 29473877
TI  - Parameter Estimation of the Thermal Network Model of a Machine Tool Spindle by
      Self-made Bluetooth Temperature Sensor Module.
AB  - Thermal characteristic analysis is essential for machine tool spindles because
      sudden failures may occur due to unexpected thermal issue. This article presents
      a lumped-parameter Thermal Network Model (TNM) and its parameter estimation
      scheme, including hardware and software, in order to characterize both the steady
      state and transient thermal behavior of machine tool spindles. For the hardware,
      the authors develop a Bluetooth Temperature Sensor Module (BTSM) which
      accompanying with three types of temperature-sensing probes (magnetic, screw, and
      probe). Its specification, through experimental test, achieves to the precision
      +/-(0.1 + 0.0029|t|)  degrees C, resolution 0.00489  degrees C, power consumption
      7 mW, and size O40 mm * 27 mm. For the software, the heat transfer
      characteristics of the machine tool spindle correlative to rotating speed are
      derived based on the theory of heat transfer and empirical formula. The
      predictive TNM of spindles was developed by grey-box estimation and experimental
      results. Even under such complicated operating conditions as various speeds and
      different initial conditions, the experiments validate that the present modeling
      methodology provides a robust and reliable tool for the temperature prediction
      with normalized mean square error of 99.5% agreement, and the present approach is
      transferable to the other spindles with a similar structure. For realizing the
      edge computing in smart manufacturing, a reduced-order TNM is constructed by
      Model Order Reduction (MOR) technique and implemented into the real-time embedded
      system.

PMID- 29473876
TI  - Temporospatial Analysis and New Players in the Immunology of Amyotrophic Lateral
      Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized
      by progressive loss of lower and upper motor neurons (MN) leading to muscle
      weakness, paralysis and eventually death. Although a highly varied etiology
      results in ALS, it broadly manifests itself as sporadic and familial forms that
      have evident similarities in clinical symptoms and disease progression. There is
      a tremendous amount of knowledge on molecular mechanisms leading to loss of MNs
      and neuromuscular junctions (NMJ) as major determinants of disease onset,
      severity and progression in ALS. Specifically, two main opposing hypotheses, the
      dying forward and dying back phenomena, exist to account for NMJ denervation. The
      former hypothesis proposes that the earliest degeneration occurs at the central
      MNs and proceeds to the NMJ, whereas in the latter, the peripheral NMJ is the
      site of precipitating degeneration progressing backwards to the MN cell body. A
      large body of literature strongly indicates a role for the immune system in
      disease onset and progression via regulatory involvement at the level of both the
      central and peripheral nervous systems (CNS and PNS). In this review, we discuss
      the earliest reported immune responses with an emphasis on newly identified
      immune players in mutant superoxide dismutase 1 (mSOD1) transgenic mice, the gold
      standard mouse model for ALS.

PMID- 29473879
TI  - In Silico-Based Repositioning of Phosphinothricin as a Novel Technetium-99m
      Imaging Probe with Potential Anti-Cancer Activity.
AB  - l-Phosphinothricin (glufosinate or 2-amino-4-((hydroxy(methyl) phosphinyl)
      butyric acid ammonium salt (AHPB)), which is a structural analog of glutamate, is
      a recognized herbicide that acts on weeds through inhibition of glutamine
      synthetase. Due to the structural similarity between phosphinothricin and some
      bisphosphonates (BPs), this study focuses on investigating the possibility of
      repurposing phosphinothricin as a bisphosphonate analogue, particularly in two
      medicine-related activities: image probing and as an anti-cancer drug. As BP is a
      competitive inhibitor of human farnesyl pyrophosphate synthase (HFPPS), in silico
      molecular docking and dynamic simulations studies were established to evaluate
      the binding and stability of phosphinothricin with HFPPS, while the results
      showed good binding and stability in the active site of the enzyme in relation to
      alendronate. For the purpose of inspecting bone-tissue accumulation of
      phosphinothricin, a technetium (99mTc)-phosphinothricin complex was developed and
      its stability and tissue distribution were scrutinized. The radioactive complex
      showed rapid, high and sustained uptake into bone tissues. Finally, the cytotoxic
      activity of phosphinothricin was tested against breast and lung cancer cells,
      with the results indicating cytotoxic activity in relation to alendronate. All
      the above results provide support for the use of phosphinothricin as a potential
      anti-cancer drug and of its technetium complex as an imaging probe.

PMID- 29473880
TI  - Assessment and Treatment of Pediatric Sleep Problems: Knowledge, Skills,
      Attitudes and Practices in a Group of Community Child Psychiatrists.
AB  - As part of a university-based quality improvement project, we aimed to evaluate
      child psychiatrists' knowledge, skills, attitudes, and practices regarding
      assessment and treatment of pediatric sleep problems. We developed a nine
      question survey of knowledge, skills, attitudes, and practices regarding
      assessing for and treating sleep complaints in pediatric patients, and
      administered this survey to child psychiatrists in training and in practice in
      the state of Missouri. Respondents reported sleep hygiene as the first-line
      treatment strategy, followed by the use of supplements or over-the-counter
      remedies. The most common barriers to evidence-based assessment and treatment of
      sleep problems were the lack of ability to obtain reliable history, and parental
      preference for medications over behavioral approaches for sleep concerns. These
      results suggest potential opportunities for enhancing knowledge regarding
      validated assessment tools and non-pharmacological treatment options for sleep
      problems. Additional research is needed to further assess the quality and type of
      sleep education provided in child psychiatry training programs.

PMID- 29473878
TI  - Alternative mRNA Splicing in the Pathogenesis of Obesity.
AB  - Alternative mRNA splicing is an important mechanism in expansion of proteome
      diversity by production of multiple protein isoforms. However, emerging evidence
      indicates that only a limited number of annotated protein isoforms by alternative
      splicing are detected, and the coding sequence of alternative splice variants
      usually is only slightly different from that of the canonical sequence.
      Nevertheless, mis-splicing is associated with a large array of human diseases.
      Previous reviews mainly focused on hereditary and somatic mutations in cis-acting
      RNA sequence elements and trans-acting splicing factors. The importance of
      environmental perturbations contributed to mis-splicing is not assessed. As
      significant changes in exon skipping and splicing factors expression levels are
      observed with diet-induced obesity, this review focuses on several well-known
      alternatively spliced metabolic factors and discusses recent advances in the
      regulation of the expressions of splice variants under the pathophysiological
      conditions of obesity. The potential of targeting the alternative mRNA mis
      splicing for obesity-associated diseases therapies will also be discussed.

PMID- 29473881
TI  - 3D Graphene-Nitrogen Doped Carbon Nanotubes Network Modified Electrode as Sensing
      Materials for the Determination of Urapidil.
AB  - In this work, a three dimensional (3D) graphene-nitrogen doped carbon nanotubes
      (G-NCNTs) network was successfully fabricated on the surface of a glassy carbon
      (GC) electrode using the pulse potential method (PPM) in a graphene oxide
      nitrogen doped carbon nanotubes (GO-NCNTs) dispersion. The morphological and
      characteristics of GO-NCNTs and G-NCNTs nanocomposites were investigated by
      atomic force microscopy (AFM), scanning electron microscopy (SEM), UV-vis
      spectroscopy, Raman spectroscopy, and electrochemical experiments. The 3DG-NCNTs
      network was applied as a new voltammetric material for the fabrication of an
      electrochemical platform for determination of urapidil. Systematic
      electrochemical tests demonstrate that the 3DG-NCNTs network modified GC
      electrode can effectively increase the response to the oxidation of urapidil.
      Under the optimum conditions, the electrochemical response was linear with
      urapidil concentrations in the range of 1.0 * 10-8~2.0 * 10-6 mol.L-1, while a
      low detection limit of 5.0 * 10-9 mol.L-1 was obtained for urapidil. Moreover,
      the proposed sensing platform exhibited good results for sensitivity,
      reproducibility, selectivity, and stability, which makes it very suitable for use
      as an ideal inexpensive and rapid analytical method applicable for complex drug
      matrices.

PMID- 29473884
TI  - Interest in Insects: The Role of Entomology in Environmental Education.
AB  - University-based outreach programs have a long history of offering environmental
      education programs to local schools, but often these lessons are not evaluated
      for their impact on teachers and students. The impact of these outreach efforts
      can be influenced by many things, but the instructional delivery method can
      affect how students are exposed to new topics or how confident teachers feel
      about incorporating new concepts into the classroom. A study was conducted with a
      series of university entomology outreach programs using insects as a vehicle for
      teaching environmental education. These programs were used to assess differences
      between three of the most common university-based outreach delivery methods
      (Scientist in the Classroom, Teacher Training Workshops, and Online Curriculum)
      for their effect on student interest and teacher self-efficacy. Surveys
      administered to 20 fifth grade classrooms found that the delivery method might
      not be as important as simply getting insects into activities. This study found
      that the lessons had a significant impact on student interest in environmental
      and entomological topics, regardless of treatment. All students found the lessons
      to be more interesting, valuable, and important over the course of the year.
      Treatment also did not influence teacher self-efficacy, as it remained high for
      all teachers.

PMID- 29473882
TI  - On the Metal Cofactor in the Tyrosinase Family.
AB  - The production of pigment in mammalian melanocytes requires the contribution of
      at least three melanogenic enzymes, tyrosinase and two other accessory enzymes
      called the tyrosinase-related proteins (Trp1 and Trp2), which regulate the type
      and amount of melanin. The last two proteins are paralogues to tyrosinase, and
      they appeared late in evolution by triplication of the tyrosinase gene.
      Tyrosinase is a copper-enzyme, and Trp2 is a zinc-enzyme. Trp1 has been more
      elusive, and the direct identification of its metal cofactor has never been
      achieved. However, due to its enzymatic activity and similarities with
      tyrosinase, it has been assumed as a copper-enzyme. Recently, recombinant human
      tyrosinase and Trp1 have been expressed in enough amounts to achieve for the
      first time their crystallization. Unexpectedly, it has been found that Trp1
      contains a couple of Zn(II) at the active site. This review discusses data about
      the metal cofactor of tyrosinase and Trps. It points out differences in the
      studied models, and it proposes some possible points accounting for the apparent
      discrepancies currently appearing. Moreover, some proposals about the possible
      flexibility of the tyrosinase family to uptake copper or zinc are discussed.

PMID- 29473885
TI  - Physicochemical Properties and Chemical Stability of beta-Carotene Bilayer
      Emulsion Coated with Bovine Serum Albumin and Arabic Gum Compared to Monolayer
      Emulsions.
AB  - beta-carotene is a lipophilic micronutrient that is considered beneficial to
      human health. However, there are some limitations in utilizing beta-carotene in
      functional foods or dietary supplements currently because of its poor water
      dispersibility and chemical stability. A new type of beta-carotene bilayer
      emulsion delivery system was prepared by a layer-by-layer electrostatic
      deposition technique, for which were chosen bovine serum albumin (BSA) as the
      inner emulsifier and Arabic gum (GA) as the outer emulsifier. The physicochemical
      properties of bilayer emulsions were mainly characterized by droplet size
      distribution, zeta potential, rheological behavior, Creaming Index (CI), and
      encapsulation ratio of beta-carotene. Besides this, the effects of processing
      conditions (pH, thermal treatment, UV radiation, strong oxidant) and storage time
      on the chemical stability of bilayer emulsions were also evaluated. The bilayer
      emulsion had a small droplet size (221.27 +/- 5.17 nm) and distribution (PDI =
      0.23 +/- 0.02), strong zeta potential (-30.37 +/- 0.71 mV), good rheological
      behavior (with the highest viscosity that could reduce the possibility of
      flocculation) and physical stability (CI = 0), high beta-carotene encapsulation
      ratio (94.35 +/- 0.71%), and low interfacial tension (40.81 +/- 0.86 mN/m). It
      also obtained better chemical stability under different environmental stresses
      when compared with monolayer emulsions studied, because it had a dense and thick
      bilayer structure.

PMID- 29473883
TI  - Emerging Nanomedicine Therapies to Counter the Rise of Methicillin-Resistant
      Staphylococcus aureus.
AB  - In a recent report, the World Health Organisation (WHO) classified antibiotic
      resistance as one of the greatest threats to global health, food security, and
      development. Methicillin-resistant Staphylococcus aureus (MRSA) remains at the
      core of this threat, with persistent and resilient strains detectable in up to
      90% of S. aureus infections. Unfortunately, there is a lack of novel antibiotics
      reaching the clinic to address the significant morbidity and mortality that MRSA
      is responsible for. Recently, nanomedicine strategies have emerged as a promising
      therapy to combat the rise of MRSA. However, these approaches have been wide
      ranging in design, with few attempts to compare studies across scientific and
      clinical disciplines. This review seeks to reconcile this discrepancy in the
      literature, with specific focus on the mechanisms of MRSA infection and how they
      can be exploited by bioactive molecules that are delivered by nanomedicines, in
      addition to utilisation of the nanomaterials themselves as antibacterial agents.
      Finally, we discuss targeting MRSA biofilms using nano-patterning technologies
      and comment on future opportunities and challenges for MRSA treatment using
      nanomedicine.

PMID- 29473886
TI  - Antioxidation and Cytoprotection of Acteoside and Its Derivatives: Comparison and
      Mechanistic Chemistry.
AB  - The study tried to explore the role of sugar-residues and mechanisms of phenolic
      phenylpropanoid antioxidants. Acteoside, along with its apioside forsythoside B
      and rhamnoside poliumoside, were comparatively investigated using various
      antioxidant assays. In three electron-transfer (ET)-based assays (FRAP, CUPRAC,
      PTIO*-scavenging at pH 4.5), the relative antioxidant levels roughly ruled as:
      acteoside >forsythoside B > poliumoside. Such order was also observed in H+
      transfer-involved PTIO*-scavenging assay at pH 7.4, and in three multiple-pathway
      involved radical-scavenging assays, i.e., ABTS+*-scavenging, DPPH*-scavenging,
      and *O2--scavenging. In UV-vis spectra, each of them displayed a red-shift at 335
      >364 nm and two weak peaks (480 and 719 nm), when mixed with Fe2+; however,
      acteoside gave the weakest absorption. In Ultra-performance liquid chromatography
      coupled with electrospray ionization quadrupole time-of-flight tandem mass
      spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis, no radical-adduct-formation (RAF)
      peak was found. MTT assay revealed that poliumoside exhibited the highest
      viability of oxidative-stressed bone marrow-derived mesenchymal stem cells. In
      conclusion, acteoside, forsythoside B, and poliumoside may be involved in
      multiple-pathways to exert the antioxidant action, including ET, H+-transfer, or
      Fe2+-chelating, but not RAF. The ET and H+-transfer may be hindered by rhamnosyl
      and apiosyl moieties; however, the Fe2+-chelating potential can be enhanced by
      two sugar-residues (especially rhamnosyl moiety). The general effect of rhamnosyl
      and apiosyl moieties is to improve the antioxidant or cytoprotective effects.

PMID- 29473887
TI  - Characterization, Stability and Biological Activity In Vitro of Cathelicidin-BF
      30 Loaded 4-Arm Star-Shaped PEG-PLGA Microspheres.
AB  - BF-30 is a single chain polypeptide of an N-segment with an alpha-helix from
      cathelicidin gene encoding, and it contains 30 amino acid residues, with a
      relative molecular mass and isoelectric point of 3637.54 and 11.79, respectively.
      Cathelicidin-BF-30 was entrapped in four-arm star-shaped poly(ethylene glycol-b
      dl-lactic acid-co-glycolic acid) block copolymers (4-arm-PEG-PLGA) by a double
      emulsion solvent-evaporation method. Three release phases of cathelicidin-BF
      30loaded 4-arm-PEG-PLGA microspheres were observed, including an initial burst
      release phase, followed by a lag phase with minimal drug release and finally a
      secondary zero-order release phase. The delivery system released BF-30 over more
      than 15 days in vitro. Furthermore, the material for preparing the microspheres
      has good biocompatibility and biodegradability. Additionally, based on the drug
      resistance of food pathogenic bacteria, the antibacterial effects of BF-30 on
      Shigella dysenteriae CMCC 51105 (Sh. dysenteriae CMCC 51105), Salmonella typhi
      (S. typhi) and Staphylococcus aureus (S. aureus) as well as the stability of the
      in vitro release of the BF-30-loded microspheres were studied. The alpha-helix
      secondary structure and antibacterial activity of released BF-30 were retained
      and compared with native peptide. These BF-30 loaded microspheres presented <10%
      hemolysis and no toxicity for HEK293T cells even at the highest tested
      concentration (150 MUg/mL), indicating that they are hemocompatible and a
      promising delivery and protection system for BF-30 peptide.

PMID- 29473889
TI  - A Qualitative Investigation to Underpin the Development of an Electronic Tool to
      Assess Nutrition Literacy in Australians Adults.
AB  - Nutrition literacy is linked to health via its influence on dietary intake. There
      is a need for a tool to assess nutrition literacy in research and dietetic
      practice. We sought guidance from nutrition professionals on topic areas and
      features of an electronic nutrition literacy assessment tool for Australian
      adults. 28 experienced nutrition professionals engaged in a range of nutrition
      and dietetic work areas participated in six focus groups using a semi-structured
      interview schedule. Data were analysed using an inductive approach using NVivo 10
      (QSR International, Pty Ltd., Doncaster, Australia, 2012). Key areas identified
      to assess nutrition literacy included specific nutrients versus foods, labels and
      packaging, construction of the diet, knowledge of the Australian Dietary
      Guidelines and Australian Guide to Healthy Eating, understanding of serve and
      portion sizes, ability to select healthier foods, and demographics such as belief
      systems and culture. Exploitation of electronic features to enhance visual and
      auditory displays, including interactive animations such as "drag and drop" and
      virtual reality situations, were discussed. This study provided insight into the
      most relevant topic areas and presentation format to assess the nutrition
      literacy of adult Australians. The visual, auditory, and interactive capacity of
      the available technology could enhance the assessment of nutrition literacy.

PMID- 29473888
TI  - Melatonin-Mediated Development of Ovine Cumulus Cells, Perhaps by Regulation of
      DNA Methylation.
AB  - Cumulus cells of pre-pubertal domestic animals are dysfunctional, perhaps due to
      age-specific epigenetic events. This study was designed to determine effects of
      melatonin treatment of donors on methylation modification of pre-pubertal cumulus
      cells. Cumulus cells from germinal vesicle stage cumulus oocyte complexes (COCs)
      were collected from eighteen lambs which were randomly divided into control group
      (C) and melatonin group given an 18 mg melatonin implant subcutaneous (M).
      Compared to the C group, the M group had higher concentrations of melatonin in
      plasma and follicular fluid (p < 0.05), greater superovulation, a higher
      proportion of fully expanded COCs, and a lower proportion of apoptotic cumulus
      cells (p < 0.05). Real-time PCR results showed that melatonin up-regulated
      expression of genes MT1, Bcl2, DNMT1, DNMT3a and DNMT3b, but down-regulated
      expression of genes p53, Caspase 3 and Bax (p < 0.05). Furthermore, melatonin
      increased FI of FITC (global methylation level) on cumulus cells (p < 0.05). To
      understand the regulation mechanism, the DNMTs promoter methylation sequence were
      analyzed. Compared to the C group, although there was less methylation at two CpG
      sites of DNMT1 (p < 0.05) and higher methylation at two CpG sites of DNMT3a (p <
      0.05), there were no significant differences in methylation of the detected DNMT1
      and DNMT3a promoter regions. However, there were lower methylation levels at five
      CpG sites of DNMT3b, which decreased methylation of detected DNMT3b promoter
      region on M group (p < 0.05). In conclusion, alterations of methylation regulated
      by melatonin may mediate development of cumulus cells in lambs.

PMID- 29473890
TI  - Printed Graphene Derivative Circuits as Passive Electrical Filters.
AB  - The objective of this study is to inkjet print resistor-capacitor (RC) low pass
      electrical filters, using a novel water-based cellulose graphene ink, and compare
      the voltage-frequency and transient behavior to equivalent circuits constructed
      from discrete passive components. The synthesized non-toxic graphene
      carboxymethyl cellulose (G-CMC) ink is deposited on mechanically flexible
      polyimide substrates using a customized printer that dispenses functionalized
      aqueous solutions. The design of the printed first-order and second-order low
      pass RC filters incorporate resistive traces and interdigitated capacitors. Low
      pass filter characteristics, such as time constant, cut-off frequency and roll
      off rate, are determined for comparative analysis. Experiments demonstrate that
      for low frequency applications (<100 kHz) the printed graphene derivative
      circuits performed as well as the circuits constructed from discrete resistors
      and capacitors for both low pass filter and RC integrator applications. The
      impact of mechanical stress due to bending on the electrical performance of the
      flexible printed circuits is also investigated.

PMID- 29473891
TI  - The Preparation, Characterization, Mechanical and Antibacterial Properties of GO
      ZnO Nanocomposites with a Poly(l-lactide)-Modified Surface.
AB  - Graphene oxide (GO) was employed for the preparation of GO-zinc oxide (ZnO). The
      hydroxyl group on the surface was exploited to trigger the l-lactide ring-opening
      polymerization. A composite material with poly(l-lactide) (PLLA) chains grafted
      to the GO-ZnO surface, GO-ZnO-PLLA, was prepared. The results demonstrated that
      the employed method allowed one-step, rapid grafting of PLLA to the GO-ZnO
      surface. The chemical structure of the GO surface was altered by improved
      dispersion of GO-ZnO in organic solvents, thus enhancing the GO-ZnO dispersion in
      the PLLA matrix and the interface bonding with PLLA. Subsequently, composite
      films, GO-ZnO-PLLA and GO-ZnO-PLLA/PLLA, were prepared. The changes in interface
      properties and mechanical properties were studied. Furthermore, the antibacterial
      performance of nano-ZnO was investigated.

PMID- 29473892
TI  - Gender Differences in the Association between Dietary Pattern and the Incidence
      of Hypertension in Middle-Aged and Older Adults.
AB  - We examined gender differences in the association between dietary patterns and
      the risk of hypertension, using the Korean Genome and Epidemiology Study data. A
      total of 5090 participants (2457 men and 2633 women) aged 40-69 years without
      hypertension at baseline were selected. Dietary patterns were obtained using
      factor analysis based on 26 food groups, evaluated by a validated semi
      quantitative food frequency questionnaire at baseline. Hypertension was defined
      as systolic blood pressure >= 140 mmHg or diastolic blood pressure >= 90 mmHg, or
      the use of antihypertensive medication using the biennial measurements.
      Multivariate Cox proportional hazards models were used to examine the
      associations between dietary patterns and hypertension. Four dietary patterns
      were extracted: coffee, fat, and sweets; prudent; whole grains and legumes; and
      traditional (men)/Western (women). Women in the highest tertile of the whole
      grains and legumes pattern scores showed a lower risk of incident hypertension
      compared with those in the lowest tertile (hazard ratio = 0.77, 95% confidence
      interval = 0.59-1.00, p-trend = 0.048). Other dietary patterns were not
      associated with hypertension in either men or women. A diet rich in whole grains
      and legumes is inversely associated with the risk of hypertension in Korean
      women, suggesting a gender difference in the association between diet and
      hypertension.

PMID- 29473894
TI  - Health- and Taste-Related Attitudes Associated with Dietary Patterns in a
      Representative Sample of Polish Girls and Young Women: A Cross-Sectional Study
      (GEBaHealth Project).
AB  - Attitudes can be predictors of certain health-related behaviours. The attitudes
      of young females towards health and taste have not been yet fully examined and
      their associations with dietary behaviours remain unclear. The aim of the study
      was to investigate if attitudes are associated with dietary patterns in a
      representative sample of Polish girls. The study population consisted of 1107
      girls, aged 13-21 and living in Poland. Attitudes were assessed using the Health
      and Taste Attitudes Scale (HTAS) and categorised as negative, neutral or
      positive. Dietary data was obtained using a Food Frequency Questionnaire. Dietary
      patterns (DPs), derived previously with a Principal Component Analysis (PCA),
      were 'Traditional Polish', 'Fruit and vegetables', 'Fast food and sweets' and
      'Dairy and fats'. The associations between attitudes and DPs were assessed using
      Spearman's correlation coefficients and logistic regression. The reference group
      were girls with neutral attitudes. Odds ratios (ORs) were adjusted for age,
      socioeconomic status (SES), and body mass index (BMI). The correlations between
      attitudes and DPs ranged from -0.28 for attitudes towards health and 'Fast food
      and sweets' and 'Traditional Polish' DPs to 0.33 for attitudes towards health and
      the 'Fruit and vegetables' DP (p < 0.05). In the logistic regression analysis,
      the strongest associations within health-related HTAS subscales were observed
      between negative attitudes towards natural products and the 'Fast food and
      sweets' DP (OR: 10.93; 95% CI: 3.32-36.01) and between positive attitudes towards
      health and the 'Fruit and vegetables' DP (OR: 5.10; 3.11-8.37). The strongest
      associations within taste-related HTAS subscales were observed between positive
      attitudes towards craving for sweet foods and the 'Traditional Polish' DP (OR:
      1.93; 1.43-2.61) and between positive attitudes towards using food as a reward
      and the 'Dairy and fats' DP (OR: 2.08; 1.22-3.55) as well as the 'Fast food and
      sweets' DP (OR: 2.07; 1.14-3.74). Positive attitudes towards health were
      associated with a pro-healthy dietary pattern characterised by the consumption of
      fruit and vegetables, while negative attitudes towards natural products as well
      as a strong craving for sweets and using food as a reward were associated with
      less healthy dietary patterns. To improve the dietary habits of girls and young
      women, positive attitudes towards health should be strengthened and supported by
      emphasizing the sensory values of pro-healthy foods.

PMID- 29473895
TI  - The Gene-Centric Content Management System and Its Application for Cognitive
      Proteomics.
AB  - The Human Proteome Project is moving into the next phase of creating and/or
      reconsidering the functional annotations of proteins using the chromosome-centric
      paradigm. This challenge cannot be solved exclusively using automated means, but
      rather requires human intelligence for interpreting the combined data. To foster
      the integration between human cognition and post-genome array a number of
      specific tools were recently developed, among them CAPER, GenomewidePDB, and The
      Proteome Browser (TPB). For the purpose of tackling the task of protein
      functional annotating the Gene-Centric Content Management System (GenoCMS) was
      expanded with new features. The goal was to enable bioinformaticans to develop
      self-made applications and to position these applets within the generalized
      informational canvas supported by GenoCMS. We report the results of GenoCMS
      enabled integration of the concordant informational flows in the chromosome
      centric framework of the human chromosome 18 project. The workflow described in
      the article can be scaled to other human chromosomes, and also supplemented with
      new tracks created by the user. The GenoCMS is an example of a project-oriented
      informational system, which are important for public data sharing.

PMID- 29473893
TI  - Restoration of Muscle Glycogen and Functional Capacity: Role of Post-Exercise
      Carbohydrate and Protein Co-Ingestion.
AB  - The importance of post-exercise recovery nutrition has been well described in
      recent years, leading to its incorporation as an integral part of training
      regimes in both athletes and active individuals. Muscle glycogen depletion during
      an initial prolonged exercise bout is a main factor in the onset of fatigue and
      so the replenishment of glycogen stores may be important for recovery of
      functional capacity. Nevertheless, nutritional considerations for optimal short
      term (3-6 h) recovery remain incompletely elucidated, particularly surrounding
      the precise amount of specific types of nutrients required. Current nutritional
      guidelines to maximise muscle glycogen availability within limited recovery are
      provided under the assumption that similar fatigue mechanisms (i.e., muscle
      glycogen depletion) are involved during a repeated exercise bout. Indeed, recent
      data support the notion that muscle glycogen availability is a determinant of
      subsequent endurance capacity following limited recovery. Thus, carbohydrate
      ingestion can be utilised to influence the restoration of endurance capacity
      following exhaustive exercise. One strategy with the potential to accelerate
      muscle glycogen resynthesis and/or functional capacity beyond merely ingesting
      adequate carbohydrate is the co-ingestion of added protein. While numerous
      studies have been instigated, a consensus that is related to the influence of
      carbohydrate-protein ingestion in maximising muscle glycogen during short-term
      recovery and repeated exercise capacity has not been established. When considered
      collectively, carbohydrate intake during limited recovery appears to primarily
      determine muscle glycogen resynthesis and repeated exercise capacity. Thus, when
      the goal is to optimise repeated exercise capacity following short-term recovery,
      ingesting carbohydrate at an amount of >=1.2 g kg body mass-1.h-1 can maximise
      muscle glycogen repletion. The addition of protein to carbohydrate during post
      exercise recovery may be beneficial under circumstances when carbohydrate
      ingestion is sub-optimal (<=0.8 g kg body mass-1.h-1) for effective restoration
      of muscle glycogen and repeated exercise capacity.

PMID- 29473896
TI  - Congenital Toxoplasmosis: A Plea for a Neglected Disease.
AB  - Maternal infection by Toxoplasma gondii during pregnancy may have serious
      consequences for the fetus, ranging from miscarriage, central nervous system
      involvement, retinochoroiditis, or subclinical infection at birth with a risk of
      late onset of ocular diseases. As infection in pregnant women is usually
      symptomless, the diagnosis relies only on serological tests. Some countries like
      France and Austria have organized a regular serological testing of pregnant
      women, some others have no prenatal program of surveillance. Reasons for these
      discrepant attitudes are many and debatable. Among them are the efficacy of
      antenatal treatment and cost-effectiveness of such a program. A significant body
      of data demonstrated that rapid onset of treatment after maternal infection
      reduces the risk and severity of fetal infection. Recent cost-effectiveness
      studies support regular screening. This lack of consensus put both pregnant women
      and care providers in a difficult situation. Another reason why congenital
      toxoplasmosis is disregarded in some countries is the lack of precise information
      about its impact on the population. Precise estimations on the burden of the
      disease can be achieved by systematic screening that will avoid bias or
      underreporting of cases and provide a clear view of its outcome.

PMID- 29473897
TI  - Design, Optimization and Characterization of a Transfersomal Gel Using Miconazole
      Nitrate for the Treatment of Candida Skin Infections.
AB  - Miconazole nitrate (MIC) is an antifungal drug used for treatment of superficial
      fungal infections. However, it has low skin permeability. Hence, the objective of
      this study was to prepare miconazole nitrate using Transfersomes to overcome the
      barrier function of the skin. MIC Transfersomes were prepared using a thin lipid
      film hydration technique. The prepared Transfersomes were evaluated with respect
      to entrapment efficiency (EE%), particle size, and quantity of in vitro drug
      released to obtain an optimized formulation. The optimized formulation of MIC
      Transfersomes was incorporated into a Carbapol 934 gel base which was evaluated
      in comparison with a marketed product (Daktarin(r) cream 2%) for drug content,
      pH, spreadability, viscosity, in vitro permeation, and in vitro and in vivo
      antifungal activity. The prepared MIC Transfersomes had a high EE% ranging from
      (67.98 +/- 0.66%) to (91.47 +/- 1.85%), with small particle sizes ranging from
      (63.5 +/- 0.604 nm) to (84.5 +/- 0.684 nm). The in vitro release study suggested
      that there was an inverse relationship between EE% and in vitro release. The
      kinetic analysis of all release profiles was found to follow Higuchi's diffusion
      model. All independent variables had a significant effect on the dependent
      variables (p-values < 0.05). The prepared MIC transfersomal gel showed higher
      antifungal activity than Daktarin(r) cream 2%. Therefore, miconazole nitrate in
      the form of Transfersomes has the ability to penetrate the skin, overcoming the
      stratum corneum barrier.

PMID- 29473898
TI  - Australia's Ongoing Legacy of Asbestos: Significant Challenges Remain Even after
      the Complete Banning of Asbestos Almost Fifteen Years Ago.
AB  - The most effective way of reducing the global burden of asbestos-related diseases
      is through the implementation of asbestos bans and minimising occupational and
      non-occupational exposure to respirable asbestos fibres. Australia's asbestos
      consumption peaked in the 1970s with Australia widely thought to have had among
      the highest per-capita asbestos consumption level of any country. Australia's
      discontinuation of all forms of asbestos and asbestos-containing products and
      materials did not occur at a single point of time. Crocidolite consumption ceased
      in the late 1960s, followed by amosite consumption stopping in the mid 1980s.
      Despite significant government reports being published in 1990 and 1999, it was
      not until the end of 2003 that a complete ban on all forms of asbestos
      (crocidolite, amosite, and chrysotile) was introduced in Australia. The sustained
      efforts of trade unions and non-governmental organisations were essential in
      forcing the Australian government to finally implement the 2003 asbestos ban.
      Trade unions and non-government organisations continue to play a key role today
      in monitoring the government's response to Australian asbestos-related disease
      epidemic. There are significant challenges that remain in Australia, despite a
      complete asbestos ban being implemented almost fifteen years ago. The Australian
      epidemic of asbestos-related disease has only now reached its peak. A total of
      16,679 people were newly diagnosed with malignant mesothelioma between 1982 and
      2016, with 84% of cases occurring in men. There has been a stabilisation of the
      age-standardised malignant mesothelioma incidence rate in the last 10 years. In
      2016, the incidence rate per 100,000 was 2.5 using the Australian standard
      population and 1.3 using the Segi world standard population. Despite Australia's
      complete asbestos ban being in place since 2003, public health efforts must
      continue to focus on preventing the devastating effects of avoidable asbestos
      related diseases, including occupational and non-occupational groups who are
      potentially at risk from exposure to respirable asbestos fibres.

PMID- 29473900
TI  - Qualification of Food Intake by the Roma Population in the Region of South
      Bohemia.
AB  - The article presents the results of a correlation study, aimed at quantifying the
      food intake of the Roma population in the South Bohemian Region. To achieve the
      goal, we applied the method of one-day dietary recall and frequency food analysis
      (non-standardized). The quantification was carried out by analysis in the
      Nutridan program. The study involved 302 Roma persons and 298 persons in the
      control group. Both groups had the same representation of males and females
      (50:50). The age categories of both sets differed; the average age of the Roma
      was lower (39.2 years) (p < 0.001). The probands from the Roma population were
      chosen with the help of the snowball method through known respondents. The
      statistical analysis shows differences in nutritional estimate between the Roma
      population and the control sample. The Roma differ in their energy intake. Both
      groups showed lower intake of sugars, below 50% total energy intake (TEI) and
      higher intake of fats, above 30% TEI. The respondents from both groups consume
      little fruits and vegetables, which may be connected with their low dietary fiber
      intake. In addition to the differences in the nutritional estimates, we recorded
      statistically significant differences in body mass index (BMI; p < 0.001), in age
      (p < 0.001), regular alimentation (p = 0) and demanding physical activities (p =
      0). In spite of the fact our groups differed in age (the Roma are younger), it
      can be assumed that the obesity of the Roma may be caused by unbalanced
      alimentation and lack of physical activities.

PMID- 29473899
TI  - Immune Responses to Dengue and Zika Viruses-Guidance for T Cell Vaccine
      Development.
AB  - Despite numerous efforts to identify the molecular and cellular effectors of the
      adaptive immunity that induce a long-lasting immunity against dengue or Zika
      virus infection, the specific mechanisms underlying such protective immunity
      remain largely unknown. One of the major challenges lies in the high level of
      dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is
      circulating. In the context of such a pre-existing DENV immunity that can
      exacerbate ZIKV infection and disease, and given the lack of appropriate
      treatment for ZIKV infection, there is an urgent need to develop an efficient
      vaccine against DENV and ZIKV. Notably, whereas several ZIKV vaccine candidates
      are currently in clinical trials, all these vaccine candidates have been designed
      to induce neutralizing antibodies as the primary mechanism of immune protection.
      Given the difficulty to elicit simultaneously high levels of neutralizing
      antibodies against the different DENV serotypes, and the potential impact of pre
      existing subneutralizing antibodies induced upon DENV infection or vaccination on
      ZIKV infection and disease, additional or alternative strategies to enhance
      vaccine efficacy, through T cell immunity, are now being considered. In this
      review, we summarize recent discoveries about cross-reactive B and T cell
      responses against DENV and ZIKV and propose guidelines for the development of
      safe and efficient T cell vaccines targeting both viruses.

PMID- 29473901
TI  - Comparative Analysis of Major Mosquito Vectors Response to Seed-Derived Essential
      Oil and Seed Pod-Derived Extract from Acacia nilotica.
AB  - Botanical metabolites are increasingly realized as potential replacements to
      chemical insecticides. In the present study, Acacia nilotica seed essential oil
      and seed pod solvent extracts were tested for bioefficacy against three important
      types of mosquitoes. Mortality was recorded 24 h post-treatment, while smoke
      toxicity of adult mosquitoes was recorded at 10 min intervals for 40 min. Seed
      pod powder was extracted with different solvents and hydrodistilled seed oil
      chemical constituents were determined by using Gas chromatography mass
      spectroscopy (GC-MS) -. Larvicidal and adulticidal efficacy of seed
      hydrodistilled essential oil and solvent extracts were tested against larval and
      adult mosquitoes. The seed hydrodistilled oil provided strong larvicidal activity
      against Anopheles stephensi, (LC50 (lethal concentration that kills 50% of the
      exposed larvae) = 5.239, LC90 (lethal concentration that kills 90% of the exposed
      larvae) = 9.713 mg/L); Aedes aegypti, (LC50 = 3.174, LC90 = 11.739 mg/L); and
      Culex quinquefasciatus, (LC50 = 4.112, LC90 = 12.325 mg/L). Smoke toxicities were
      82% in Cx. quinquefasciatus, 90% in Ae. aegypti, and 80% mortality in An.
      stephensi adults, whereas 100% mortality was recorded for commercial mosquito
      coil. The GC-MS profile of seed essential oil from A. nilotica showed the
      presence of hexadecane (18.440%) and heptacosane (15.914%), which are the main
      and active compounds, and which may be involved in insecticidal activity. Overall
      findings suggest that the seed oil showed strong mosquitocidal activity against
      mosquito vectors and therefore may provide an ecofriendly replacement to chemical
      insecticides.

PMID- 29473902
TI  - Advances in Residential Design Related to the Influence of Geomagnetism.
AB  - Since the origin of the Modern Movement, there has been a basic commitment to
      improving housing conditions and the well-being of occupants, especially given
      the prediction that 2/3 of humanity will reside in cities by 2050. Moreover, a
      compact model of the city with tall buildings and urban densification at this
      scale will be generated. Continuous constructive and technological advances have
      developed solid foundations on safety, energy efficiency, habitability, and
      sustainability in housing design. However, studies on improving the quality of
      life in these areas continue to be a challenge for architects and engineers. This
      paper seeks to contribute health-related information to the study of residential
      design, specifically the influence of the geomagnetic field on its occupants.
      After compiling information on the effects of geomagnetic fields from different
      medical studies over 23 years, a case study of a 16-story high-rise building is
      presented, with the goal of proposing architectural design recommendations for
      long-term occupation in the same place. The purpose of the present work is three
      fold: first, to characterize the geomagnetic field variability of buildings;
      second, to identify the causes and possible related mechanisms; and third, to
      define architectural criteria on the arrangement of uses and constructive
      elements for housing.

PMID- 29473904
TI  - Sinus Bradycardia in Carriers of the SCN5A-1795insD Mutation: Unraveling the
      Mechanism through Computer Simulations.
AB  - The SCN5A gene encodes the pore-forming alpha-subunit of the ion channel that
      carries the cardiac fast sodium current (INa). The 1795insD mutation in SCN5A
      causes sinus bradycardia, with a mean heart rate of 70 beats/min in mutation
      carriers vs. 77 beats/min in non-carriers from the same family (lowest heart rate
      41 vs. 47 beats/min). To unravel the underlying mechanism, we incorporated the
      mutation-induced changes in INa into a recently developed comprehensive
      computational model of a single human sinoatrial node cell (Fabbri-Severi model).
      The 1795insD mutation reduced the beating rate of the model cell from 74 to 69
      beats/min (from 49 to 43 beats/min in the simulated presence of 20 nmol/L
      acetylcholine). The mutation-induced persistent INa per se resulted in a
      substantial increase in beating rate. This gain-of-function effect was almost
      completely counteracted by the loss-of-function effect of the reduction in INa
      conductance. The further loss-of-function effect of the shifts in steady-state
      activation and inactivation resulted in an overall loss-of-function effect of the
      1795insD mutation. We conclude that the experimentally identified mutation
      induced changes in INa can explain the clinically observed sinus bradycardia.
      Furthermore, we conclude that the Fabbri-Severi model may prove a useful tool in
      understanding cardiac pacemaker activity in humans.

PMID- 29473905
TI  - The In Vitro Effects of Enzymatic Digested Gliadin on the Functionality of the
      Autophagy Process.
AB  - Gliadin, the alcohol-soluble protein fraction of wheat, contains the factor toxic
      for celiac disease (CD), and its toxicity is not reduced by digestion with gastro
      pancreatic enzymes. Importantly, it is proved that an innate immunity to gliadin
      plays a key role in the development of CD. The immune response induces epithelial
      stress and reprograms intraepithelial lymphocytes into natural killer (NK)-like
      cells, leading to enterocyte apoptosis and an increase in epithelium
      permeability. In this contribution, we have reported that in Caco-2 cells the
      administration of enzymatically digested gliadin (PT-gliadin) reduced
      significantly the expression of the autophagy-related marker LC3-II. Furthermore,
      electron and fluorescent microscope analysis suggested a compromised
      functionality of the autophagosome apparatus. The rescue of the dysregulated
      autophagy process, along with a reduction of PT-gliadin toxicity, was obtained
      with a starvation induction protocol and by 3-methyladenine administration, while
      rapamycin, a well-known autophagy inducer, did not produce a significant
      improvement in the clearance of extra- and intra-cellular fluorescent PT-gliadin
      amount. Altogether, our results highlighted the possible contribution of the
      autophagy process in the degradation and in the reduction of extra-cellular
      release of gliadin peptides and suggest novel molecular targets to counteract
      gliadin-induced toxicity in CD.

PMID- 29473906
TI  - Risk Factors of Extended-Spectrum beta-Lactamase Producing Enterobacteriaceae
      Occurrence in Farms in Reunion, Madagascar and Mayotte Islands, 2016-2017.
AB  - In South Western Indian ocean (IO), Extended-Spectrum beta-Lactamase producing
      Enterobacteriaceae (ESBL-E) are a main public health issue. In livestock, ESBL-E
      burden was unknown. The aim of this study was estimating the prevalence of ESBL-E
      on commercial farms in Reunion, Mayotte and Madagascar and genes involved.
      Secondly, risk factors of ESBL-E occurrence in broiler, beef cattle and pig farms
      were explored. In 2016-2017, commercial farms were sampled using boot swabs and
      samples stored at 4  degrees C before microbiological analysis for phenotypical
      ESBL-E and gene characterization. A dichotomous questionnaire was performed.
      Prevalences observed in all production types and territories were high, except
      for beef cattle in Reunion, which differed significantly. The most common ESBL
      gene was blaCTX-M-1. Generalized linear models explaining ESBL-E occurrence
      varied between livestock production sectors and allowed identifying main
      protective (e.g., water quality control and detergent use for cleaning) and risk
      factors (e.g., recent antibiotic use, other farmers visiting the exploitation,
      pet presence). This study is the first to explore tools for antibiotic resistance
      management in IO farms. It provides interesting hypothesis to explore about
      antibiotic use in IO territories and ESBL-E transmission between pig, beef cattle
      and humans in Madagascar.

PMID- 29473903
TI  - The Role of Culex pipiens L. (Diptera: Culicidae) in Virus Transmission in
      Europe.
AB  - Over the past three decades, a range of mosquito-borne viruses that threaten
      public and veterinary health have emerged or re-emerged in Europe. Mosquito
      surveillance activities have highlighted the Culex pipiens species complex as
      being critical for the maintenance of a number of these viruses. This species
      complex contains morphologically similar forms that exhibit variation in
      phenotypes that can influence the probability of virus transmission. Critical
      amongst these is the choice of host on which to feed, with different forms
      showing different feeding preferences. This influences the ability of the
      mosquito to vector viruses and facilitate transmission of viruses to humans and
      domestic animals. Biases towards blood-feeding on avian or mammalian hosts have
      been demonstrated for different Cx. pipiens ecoforms and emerging evidence of
      hybrid populations across Europe adds another level of complexity to virus
      transmission. A range of molecular methods based on DNA have been developed to
      enable discrimination between morphologically indistinguishable forms, although
      this remains an active area of research. This review provides a comprehensive
      overview of developments in the understanding of the ecology, behaviour and
      genetics of Cx. pipiens in Europe, and how this influences arbovirus
      transmission.

PMID- 29473909
TI  - Assessment of Pressure Sources and Water Body Resilience: An Integrated Approach
      for Action Planning in a Polluted River Basin.
AB  - The present study develops an integrated methodology combining the results of the
      water-quality classification, according to the Water Framework Directive
      2000/60/EC-WFD, with those of a mathematical integrity model. It is able to
      analyse the potential anthropogenic impacts on the receiving water body and to
      help municipal decision-makers when selecting short/medium/long-term strategic
      mitigation actions to be performed in a territory. Among the most important
      causes of water-quality degradation in a river, the focus is placed on pollutants
      from urban wastewater. In particular, the proposed approach evaluates the
      efficiency and the accurate localisation of treatment plants in a basin, as well
      as the capacity of its river to bear the residual pollution loads after the
      treatment phase. The methodology is applied to a sample catchment area, located
      in northern Italy, where water quality is strongly affected by high population
      density and by the presence of agricultural and industrial activities. Nearly 10
      years of water-quality data collected through official monitoring are considered
      for the implementation of the system. The sample basin shows different real and
      potential pollution conditions, according to the resilience of the river and
      surroundings, together with the point and diffuse pressure sources acting on the
      receiving body.

PMID- 29473910
TI  - A Method for Dynamically Selecting the Best Frequency Hopping Technique in
      Industrial Wireless Sensor Network Applications.
AB  - Industrial wireless applications often share the communication channel with other
      wireless technologies and communication protocols. This coexistence produces
      interferences and transmission errors which require appropriate mechanisms to
      manage retransmissions. Nevertheless, these mechanisms increase the network
      latency and overhead due to the retransmissions. Thus, the loss of data packets
      and the measures to handle them produce an undesirable drop in the QoS and hinder
      the overall robustness and energy efficiency of the network. Interference
      avoidance mechanisms, such as frequency hopping techniques, reduce the need for
      retransmissions due to interferences but they are often tailored to specific
      scenarios and are not easily adapted to other use cases. On the other hand, the
      total absence of interference avoidance mechanisms introduces a security risk
      because the communication channel may be intentionally attacked and interfered
      with to hinder or totally block it. In this paper we propose a method for
      supporting the design of communication solutions under dynamic channel
      interference conditions and we implement dynamic management policies for
      frequency hopping technique and channel selection at runtime. The method
      considers several standard frequency hopping techniques and quality metrics, and
      the quality and status of the available frequency channels to propose the best
      combined solution to minimize the side effects of interferences. A simulation
      tool has been developed and used in this work to validate the method.

PMID- 29473907
TI  - Pharmacological Inhibition of Protein Kinase C Reduces West Nile Virus
      Replication.
AB  - Flaviviruses are relevant animal and human pathogens that include West Nile virus
      (WNV), Japanese encephalitis virus, dengue virus, or Zika virus, among others.
      Currently, no licensed therapy is available to fight flaviviral infections.
      Protein kinases C (PKCs) constitute a family of multifunctional lipid-dependent
      isoenzymes that regulate a wide variety of cellular processes (apoptosis,
      differentiation, proliferation, cellular transformation, motility, adhesion,
      etc.) being currently considered at the front line of drug development for the
      treatment of diverse human disorders. PKCs have also been implicated in different
      steps during viral replication; however, nowadays, results regarding their role
      in flavivirus replication are controversial. Here we demonstrate that calphostin
      C and chelerythrine, two broad-PKC inhibitors that target conventional, novel and
      atypical PKCs, significantly inhibit WNV multiplication in cell culture without
      affecting cell viability. A reduction of viral yields was observed in treated
      cells when compared with mock-treated cells. Likewise, immunofluorescence
      detection of viral enveloped E protein was reduced in treated cells, as was the
      amount of viral RNA released to the supernatant, mainly in those treated with
      chelerythrine. On the other hand, two PKC inhibitors specific for conventional
      and novel isoforms (staurosporine and enzastaurine) did not show any significant
      effect in WNV multiplication. These results suggested that PKCs, more probably
      atypical PKCs, are likely involved in WNV multiplication, although both broad
      spectrum tested drugs seem to act through different mechanisms, and point to them
      as potential antiviral candidates for WNV, as well as for other related
      flaviviruses.

PMID- 29473908
TI  - l-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal
      Muscle Mass and Function.
AB  - Skeletal muscle wasting, associated with aging, may be regulated by the
      inflammatory cytokines as well as by insulin-like growth factor 1 (IGF-1). l
      carnitine possesses anti-inflammatory properties and increases plasma IGF-1
      concentration, leading to the regulation of the genes responsible for protein
      catabolism and anabolism. The purpose of the present study was to evaluate the
      effect of a 24-week l-carnitine supplementation on serum inflammatory markers,
      IGF-1, body composition and skeletal muscle strength in healthy human subjects
      over 65 years of age. Women between 65 and 70 years of age were supplemented for
      24 weeks with either 1500 mg l-carnitine-l-tartrate or an isonitrogenous placebo
      per day in a double-blind fashion. Before and after the supplementation protocol,
      body mass and composition, as well as knee extensor and flexor muscle strength
      were determined. In the blood samples, free carnitine, interleukin-6, tumor
      necrosis factor-alpha, C-reactive protein and IGF-1 were determined. A marked
      increase in free plasma carnitine concentration was observed due to l-carnitine
      supplementation. No substantial changes in other parameters were noted. In the
      current study, supplementation for 24 weeks affected neither the skeletal muscle
      strength nor circulating markers in healthy women over 65 years of age. Positive
      and negative aspects of l-carnitine supplementation need to be clarified.

PMID- 29473911
TI  - Methionine-Capped Gold Nanoclusters as a Fluorescence-Enhanced Probe for
      Cadmium(II) Sensing.
AB  - Gold nanoclusters (Au NCs) have been considered as novel heavy metal ions sensors
      due to their ultrafine size, photo-stability and excellent fluorescent
      properties. In this study, a green and facile method was developed for the
      preparation of fluorescent water-soluble gold nanoclusters with methionine as a
      stabilizer. The nanoclusters emit orange fluorescence with excitation/emission
      peaks at 420/565 nm and a quantum yield of about 1.46%. The fluorescence of the
      Au NCs is selectively and sensitively enhanced by addition of Cd(II) ions
      attributed to the Cd(II) ion-induced aggregation of nanoclusters. This finding
      was further used to design a fluorometric method for the determination of Cd(II)
      ions, which had a linear response in the concentration range from 50 nM to 35 MUM
      and a detection limit of 12.25 nM. The practicality of the nanoprobe was
      validated in various environmental water samples and milk powder samples, with a
      fairly satisfactory recovery percent.

PMID- 29473912
TI  - Application of Improved 5th-Cubature Kalman Filter in Initial Strapdown Inertial
      Navigation System Alignment for Large Misalignment Angles.
AB  - In view of the fact the accuracy of the third-degree Cubature Kalman Filter (CKF)
      used for initial alignment under large misalignment angle conditions is
      insufficient, an improved fifth-degree CKF algorithm is proposed in this paper.
      In order to make full use of the innovation on filtering, the innovation
      covariance matrix is calculated recursively by an innovative sequence with an
      exponent fading factor. Then a new adaptive error covariance matrix scaling
      algorithm is proposed. The Singular Value Decomposition (SVD) method is used for
      improving the numerical stability of the fifth-degree CKF in this paper. In order
      to avoid the overshoot caused by excessive scaling of error covariance matrix
      during the convergence stage, the scaling scheme is terminated when the gradient
      of azimuth reaches the maximum. The experimental results show that the improved
      algorithm has better alignment accuracy with large misalignment angles than the
      traditional algorithm.

PMID- 29473913
TI  - Establishment of the Volatile Signature of Wine-Based Aromatic Vinegars Subjected
      to Maceration.
AB  - The flavoring of vinegars with aromatic fruits and medicinal herbs is a practice
      with increasing trend mostly in countries with oenological tradition, resulting
      in a product of improved quality and consumer attractiveness. This study was
      directed towards the evaluation of the impact of the maceration process on the
      volatile signature of wine-based aromatic vinegars (WBAVs). The evaluation was
      performed using solid phase microextraction (SPME) combined with gas
      chromatography combined with mass spectrometry (GC-MS). Experimental parameters
      influencing headspace solid (HS)-SPME extraction efficiency, were optimized using
      an univariate experimental design. The best results were achieved using a
      polydimethylsiloxane (PDMS) fiber, 10 mL of vinegar sample, at 50  degrees C for
      30 min of extraction. This way One hundred and three volatile organic compounds
      (VOCs), belonging to different chemical families including ethyl esters (37),
      higher alcohols (20), fatty acids (10), terpenoids (23), carbonyl compounds
      (six), lactones (five) and volatile phenols (two), were identified in wine
      vinegar (control) and WBAV. As far as we know, 34 of these VOCs are reported for
      the first time in macerated vinegars. Higher alcohols and lactones are the major
      chemical families in WBAV macerated with apple, whereas terpenoids are
      predominant in WBAV macerated with banana. The obtained data represent a suitable
      tool to guarantee the authenticity and genuineness of WBAV, as well as to promote
      the production of WBAV with improved sensorial and organoleptic properties. To
      the best of our knowledge, there are no reported studies dealing with the
      volatile signature of WBAV enriched with banana, passion fruit, apple and
      pennyroyal.

PMID- 29473914
TI  - Fe3O4 Nanoparticles in Targeted Drug/Gene Delivery Systems.
AB  - Fe3O4 nanoparticles (NPs), the most traditional magnetic nanoparticles, have
      received a great deal of attention in the biomedical field, especially for
      targeted drug/gene delivery systems, due to their outstanding magnetism,
      biocompatibility, lower toxicity, biodegradability, and other features. Naked
      Fe3O4 NPs are easy to aggregate and oxidize, and thus are often made with various
      coatings to realize superior properties for targeted drug/gene delivery. In this
      review, we first list the three commonly utilized synthesis methods of Fe3O4 NPs,
      and their advantages and disadvantages. In the second part, we describe coating
      materials that exhibit noticeable features that allow functionalization of Fe3O4
      NPs and summarize their methods of drug targeting/gene delivery. Then our efforts
      will be devoted to the research status and progress of several different
      functionalized Fe3O4 NP delivery systems loaded with chemotherapeutic agents, and
      we present targeted gene transitive carriers in detail. In the following section,
      we illuminate the most effective treatment systems of the combined drug and gene
      therapy. Finally, we propose opportunities and challenges of the clinical
      transformation of Fe3O4 NPs targeting drug/gene delivery systems.

PMID- 29473917
TI  - Enhanced Humidity Sensitivity with Silicon Nanopillar Array by UV Light.
AB  - The sensitivity of silicon nanopillar array for relative humidity (RH) with UV
      illumination was investigated in this work. The silicon nanopillar array was
      prepared by nanosphere lithography. Electrical measurements were performed on its
      sensing performance with and without UV irradiation. It was found that UV light
      improved the humidity sensitivity with different UV light wavelengths and power.
      The sensor response and recovery time were reduced. Furthermore, the turn-on
      threshold voltage and the operating voltage both decreased. These sensing
      characteristics can mainly be attributed to the electron-hole pairs generated by
      UV light. These electron-hole pairs promote the adsorption and desorption
      processes. The results indicate that silicon nanopillar array materials with UV
      irradiation might be competitive as novel sensing materials for fabricating
      humidity sensors with high performances.

PMID- 29473916
TI  - Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue
      Thermogenic Gene Expression in Mice Fed High-Fat Diets.
AB  - Dietary fatty acids play important roles in the regulation of fat accumulation or
      metabolic phenotype of adipocytes, either as brown or beige fat. However, a
      systematic comparison of effects of diets with different composition of 18-C
      fatty acids on browning/beiging phenotype has not been done. In this study, we
      compared the effects of different dietary fats, rich in specific 18-carbon fatty
      acids, on thermogenesis and lipid metabolism. Male C57BL/6 mice were fed a
      control diet containing 5.6% kcal fat from lard and 4.4% kcal fat from soybean
      oil (CON) or high-fat diets (HFD) containing 25% kcal from lard and 20% kcal fat
      from shea butter (stearic acid-rich fat; SHB), olive oil (oleic acid-rich oil;
      OO), safflower oil (linoleic acid-rich oil; SFO), or soybean oil (mixed oleic,
      linoleic, and alpha-linolenic acids; SBO) ad libitum for 12 weeks, with or
      without a terminal 4-h norepinephrine (NE) treatment. When compared to SHB,
      feeding OO, SFO, and SBO resulted in lower body weight gain. The OO fed group had
      the highest thermogenesis level, which resulted in lower body fat accumulation
      and improved glucose and lipid metabolism. Feeding SFO downregulated expression
      of lipid oxidation-related genes and upregulated expression of lipogenic genes,
      perhaps due to its high n-6:n-3 ratio. In general, HFD-feeding downregulated Ucp1
      expression in both subcutaneous and epididymal white adipose tissue, and
      suppressed NE-induced Pgc1a expression in brown adipose tissue. These results
      suggest that the position of double bonds in dietary fatty acids, as well as the
      quantity of dietary fat, may have a significant effect on the regulation of
      oxidative and thermogenic conditions in vivo.

PMID- 29473918
TI  - Metal Nanoparticles/Porous Silicon Microcavity Enhanced Surface Plasmon Resonance
      Fluorescence for the Detection of DNA.
AB  - A porous silicon microcavity (PSiMC) with resonant peak wavelength of 635 nm was
      fabricated by electrochemical etching. Metal nanoparticles (NPs)/PSiMC enhanced
      fluorescence substrates were prepared by the electrostatic adherence of Au NPs
      that were distributed in PSiMC. The Au NPs/PSiMC device was used to characterize
      the target DNA immobilization and hybridization with its complementary DNA
      sequences marked with Rhodamine red (RRA). Fluorescence enhancement was observed
      on the Au NPs/PSiMC device substrate; and the minimum detection concentration of
      DNA ran up to 10 pM. The surface plasmon resonance (SPR) of the MC substrate;
      which is so well-positioned to improve fluorescence enhancement rather the
      fluorescence enhancement of the high reflection band of the Bragg reflector;
      would welcome such a highly sensitive in biosensor.

PMID- 29473919
TI  - Leader-Follower Formation Control of UUVs with Model Uncertainties, Current
      Disturbances, and Unstable Communication.
AB  - Unmanned underwater vehicles (UUVs) have rapidly developed as mobile sensor
      networks recently in the investigation, survey, and exploration of the underwater
      environment. The goal of this paper is to develop a practical and efficient
      formation control method to improve work efficiency of multi-UUV sensor networks.
      Distributed leader-follower formation controllers are designed based on a state
      feedback and consensus algorithm. Considering that each vehicle is subject to
      model uncertainties and current disturbances, a second-order integral UUV model
      with a nonlinear function is established using the state feedback linearized
      method under current disturbances. For unstable communication among UUVs,
      communication failure and acoustic link noise interference are considered. Two
      layer random switching communication topologies are proposed to solve the problem
      of communication failure. For acoustic link noise interference, accurate
      representation of valid communication information and noise stripping when
      designing controllers is necessary. Effective communication topology weights are
      designed to represent the validity of communication information interfered by
      noise. Utilizing state feedback and noise stripping, sufficient conditions for
      design formation controllers are proposed to ensure UUV formation achieves
      consensus under model uncertainties, current disturbances, and unstable
      communication. The stability of formation controllers is proven by the Lyapunov
      Razumikhin theorem, and the validity is verified by simulation results.

PMID- 29473915
TI  - Infection and Transport of Herpes Simplex Virus Type 1 in Neurons: Role of the
      Cytoskeleton.
AB  - Herpes simplex virus type 1 (HSV-1) is a neuroinvasive human pathogen that has
      the ability to infect and replicate within epithelial cells and neurons and
      establish a life-long latent infection in sensory neurons. HSV-1 depends on the
      host cellular cytoskeleton for entry, replication, and exit. Therefore, HSV-1 has
      adapted mechanisms to promote its survival by exploiting the microtubule and
      actin cytoskeletons to direct its active transport, infection, and spread between
      neurons and epithelial cells during primary and recurrent infections. This review
      will focus on the currently known mechanisms utilized by HSV-1 to harness the
      neuronal cytoskeleton, molecular motors, and the secretory and exocytic pathways
      for efficient virus entry, axonal transport, replication, assembly, and exit from
      the distinct functional compartments (cell body and axon) of the highly polarized
      sensory neurons.

PMID- 29473921
TI  - Concurrent presence of on- and off-pathway folding intermediates of apoflavodoxin
      at physiological ionic strength.
AB  - Flavodoxins have a protein topology that can be traced back to the universal
      ancestor of the three kingdoms of life. Proteins with this type of architecture
      tend to temporarily misfold during unassisted folding to their native state and
      form intermediates. Several of these intermediate species are molten globules
      (MGs), which are characterized by a substantial amount of secondary structure,
      yet without the tertiary side-chain packing of natively folded proteins. An off
      pathway MG is formed at physiological ionic strength in the case of the F44Y
      variant of Azotobacter vinelandii apoflavodoxin (i.e., flavodoxin without flavin
      mononucleotide (FMN)). Here, we show that at this condition actually two folding
      species of this apoprotein co-exist at equilibrium. These species were detected
      by using a combination of FMN fluorescence quenching upon cofactor binding to the
      apoprotein and of polarized time-resolved tryptophan fluorescence spectroscopy.
      Besides the off-pathway MG, we observe the simultaneous presence of an on-pathway
      folding intermediate, which is native-like. Presence of concurrent intermediates
      at physiological ionic strength enables future exploration of how aspects of the
      cellular environment, like for example involvement of chaperones, affect these
      species.

PMID- 29473920
TI  - Prevalence and associations of presenting near-vision impairment in the
      Australian National Eye Health Survey.
AB  - PurposeTo describe the prevalence and associations of presenting near vision
      impairment (NVI) in Indigenous and non-Indigenous Australians.MethodsA sample of
      3098 non-Indigenous Australians (aged 50-98 years) and 1738 Indigenous
      Australians (aged 40-92 years) living in 30 randomly selected Australian sites
      were examined as part of the population-based National Eye Health Survey (NEHS).
      Binocular presenting NVI was defined as near vision worse than N8
      (20/50).ResultsIn total, 4817 participants (99.6% of the total sample, comprising
      3084 non-Indigenous Australians and 1733 Indigenous Australians) had complete
      data on near visual acuity. The overall weighted prevalence of presenting NVI was
      21.6% (95% CI: 19.6, 23.8) in non-Indigenous Australians and 34.7% (95% CI: 29.2,
      40.8) among Indigenous Australians. In the non-Indigenous population, higher odds
      of presenting NVI were associated with older age (OR=1.68 per 10 years, P<0.001),
      fewer years of education (OR=0.95 per year, P<0.001) and residing in Remote
      geographical areas (OR=1.71, P=0.003) after multivariate adjustments. Among
      Indigenous Australians, older age (OR=1.69 per 10 years, P<0.001), fewer years of
      education (OR=0.91 per year, P=0.003) and residing in Inner Regional (OR=2.01,
      P=0.008), Outer Regional (OR=2.17, P=<0.001) and Remote geographical areas
      (OR=1.72, P=0.03) were associated with greater odds of presenting
      NVI.ConclusionsNVI represents a notable public health concern in Australia,
      affecting approximately 20% of non-Indigenous Australian and one-third of
      Indigenous Australian adults.

PMID- 29473922
TI  - Kinetics of the reaction of CO3-(H2O)n, n = 0, 1, 2, with nitric acid, a key
      reaction in tropospheric negative ion chemistry.
AB  - A significant fraction of nitrate in the troposphere is formed in the reactions
      of HNO3 with the carbonate radical anion CO3- and the mono- and dihydrated
      species CO3-(H2O)1,2. A reaction mechanism was proposed in earlier flow reactor
      studies, which is investigated here in more detail by quantum chemical
      calculations and experimental reactivity studies of mass selected ions under
      ultra-high vacuum conditions. Bare CO3- forms NO3-(OH) as well as NO3-, with a
      total rate coefficient of 1.0 * 10-10 cm3 s-1. CO3-(H2O) in addition affords
      stabilization of the NO3-(HCO3) collision complex, and thermalized CO3-(H2O)
      reacts with a total rate coefficient of 6.3 * 10-10 cm3 s-1. A second solvent
      molecule quenches the reaction, and only black-body radiation induced
      dissociation is observed for CO3-(H2O)2, with an upper limit of 6.0 * 10-11 cm3 s
      1 for any potential bimolecular reaction channel. The rate coefficients obtained
      under ultra-high vacuum conditions are smaller than in the earlier flow reactor
      studies, due to the absence of stabilizing collisions, which also has a strong
      effect on the product branching ratio. Quantum chemical calculations corroborate
      the mechanism proposed by Mohler and Arnold. The reaction proceeds through a
      proton-transferred NO3-(HCO3) collision complex, which can rearrange to NO3
      (OH)(CO2). The weakly bound CO2 easily evaporates, followed by evaporation of the
      more strongly attached OH, if sufficient energy is available.

PMID- 29473923
TI  - Sum-frequency vibrational spectroscopy of limonene chiral liquids due to the
      nonadiabatic effect.
AB  - Using quantum computations we study sum-frequency vibrational spectroscopy of
      limonene chiral liquids due to the nonadiabatic effect in the non-resonant case
      for the first time. The nonadiabatic effect has an important impact on non
      resonant antisymmetric polarizability and chiral sum-frequency vibrational
      spectroscopy. The theoretical spectroscopy agrees with the experimental
      spectroscopy. However, the nonadiabatic effect only has a small influence on non
      resonant Raman. Bulk sum-frequency vibrational spectroscopy may become a powerful
      method of investigating the nonadiabatic effect and the nonradiative transition
      between excited electronic states for chiral molecules.

PMID- 29473924
TI  - Selective interface transparency in graphene nanoribbon based molecular
      junctions.
AB  - A clear understanding of electrode-molecule interfaces is a prerequisite for the
      rational engineering of future generations of nanodevices that will rely on
      single-molecule coupling between components. With a model system, we reveal a
      peculiar dependence on interfaces in all graphene nanoribbon-based carbon
      molecular junctions. The effect can be classified into two types depending on the
      intrinsic feature of the embedded core graphene nanoflake (GNF). For metallic
      GNFs with |NA - NB| = 1, good/poor contact transparency occurs when the core
      device aligns with the center/edge of the electrode. The situation is reversed
      when a semiconducting GNF is the device, where NA = NB. These results may shed
      light on the design of real connecting components in graphene-based nanocircuits.

PMID- 29473925
TI  - Rational design of 3D inverse opal heterogeneous composite microspheres as
      excellent visible-light-induced NO2 sensors at room temperature.
AB  - The lower gas sensitivity, humidity dependence of the gas sensing properties, and
      long recovery times of room-temperature gas sensors severely limit their
      applications. Herein, to address these issues, a series of 3D inverse opal (IO)
      In2O3-ZnO heterogeneous composite microspheres (HCMs) are fabricated by
      ultrasonic spray pyrolysis (USP) employing self-assembled sulfonated polystyrene
      (S-PS) spheres as a sacrificial template. The 3D IO In2O3-ZnO HCMs possess highly
      ordered 3D inverse opal structures and bimodal (meso-scale and macro-scale)
      pores, which can provide large accessible surface areas and rapid mass transfer,
      resulting in enhanced gas sensing characteristics. Furthermore, the 3D IO
      architecture and n-n heterojunctions can extend the photoabsorption range to the
      visible light area, effectively prolonging the lifetimes of photo-generated
      charge carriers, and can increase separation of visible light-generated charges.
      As a result, the as-prepared 3D IO In2O3-ZnO HCMs deliver excellent NO2 sensing
      performance under visible light irradiation at room temperature, such as high
      sensitivity (Rgas/Rair = 54.3 to 5 ppm NO2), low detection limit (250 ppb), fast
      recovery time (188 s), excellent selectivity and humidity independence. These
      enhanced photo-electronic gas sensing properties are attributed to the
      combination of highly ordered 3D IO microspheres and In2O3-ZnO heterogeneous
      composites.

PMID- 29473926
TI  - Emergence of photoluminescence enhancement of Eu3+ doped BiOCl single-crystalline
      nanosheets at reduced vertical dimensions.
AB  - Here, we report that a reduction in scale leads to an enhancement in the
      photoluminescence (PL) of Eu3+ doped BiOCl nanosheets, challenging the long
      standing notion that PL is inevitably suppressed at a scale of tens of
      nanometers. The oriented depolarization effect of layered ferroelectrics was
      utilized for the first time to improve the PL efficiency of lanthanide doped
      nanomaterials. The probing effect of the electric dipole transitions of the Eu3+
      ions and their PL measurements provides evidence that the depolarization field
      and the PL of Eu3+ ions increase synchronously as the thickness of the BiOCl
      single-crystalline nanosheets decreases from hundreds to tens of nanometers. We
      show that the scale-dependent internal electric field (IEF) induced by the
      depolarization field as well as its excitation field enhancement are responsible
      for the appearance of an abnormal scale-dependent PL enhancement. This finding
      may be useful for the development of low-dimensional material systems with
      enhanced photophysical properties, relevant for use in new nano-optoelectronic
      devices.

PMID- 29473927
TI  - Screening and identification of inhibitors of advanced glycation endproduct
      formation from microalgal extracts.
AB  - The formation and accumulation of advanced glycation endproducts (AGEs) have been
      implicated in the pathogenesis of many chronic diseases, such as aging,
      Alzheimer's disease, diabetes and diabetic complications. The present study was
      aimed to investigate the inhibitory effects of the extracts from nine microalgae
      on the formation of AGEs by using in vitro models and identify key antiglycation
      constituents of the microalgae. A BSA-glucose model with simulated physiological
      conditions was used to evaluate the inhibitory effect on total AGE formation. A
      BSA-MGO model was used to study the inhibitory activity against the dicarbonyl
      induced AGE formation. The results showed that the aqueous acetone extracts
      exhibited stronger antiglycation activity than the other extracts (ethyl acetate
      and dichloromethane) and that the marine microalgal extracts were generally more
      effective than the freshwater ones. Their inhibitory rates ranged from >60% to
      90% when used at a concentration of 0.5 mg mL-1. HPLC-DAD and UPLC-Q-TOF-MSE
      analyses revealed that fucoxanthin was likely the principal component which
      contributed to the observed antiglycation activity. Further analysis established
      a highly significant positive correlation (R2 > 0.95) between the fucoxanthin
      content and the antiglycation activity of the aqueous acetone extracts. This is
      the first report on the antiglycation activity of fucoxanthin. The findings of
      the present study have not only identified a promising inhibitor of AGE
      formation, but have also identified a valuable natural source of this
      phytochemical which possesses great potential to be developed as functional food
      ingredients and pharmaceutical products to help reduce health risks associated
      with AGEs.

PMID- 29473928
TI  - A novel IrNi@PdIr/C core-shell electrocatalyst with enhanced activity and
      durability for the hydrogen oxidation reaction in alkaline anion exchange
      membrane fuel cells.
AB  - Herein, a novel non-platinum core-shell catalyst, namely, IrNi@PdIr/C was
      prepared via a galvanic replacement reaction; it exhibits enhanced hydrogen
      oxidation activity and excellent stability under alkaline conditions.
      Electrochemical experiments demonstrated that the mass and specific activities at
      50 mV of IrNi@PdIr/C are 2.1 and 2.2 times that of commercial Pt/C in 0.1 M KOH
      at 298 K, respectively. Moreover, accelerated degradation tests have shown that
      the electrochemically active surface area (ECSA) of IrNi@PdIr/C reduces by only
      5.1%, which is almost 4 times less than that of commercial Pt/C and the mass
      activity at 50 mV of IrNi@PdIr/C after 2000 potential cycles is still 1.8 times
      higher than that of aged Pt/C. XRD and XPS analysis suggest that the enhanced HOR
      activity is attributed to the weakening of the hydrogen binding to the PdIr
      overlayers induced by the IrNi core. The better stability to potential cycling
      can be associated with the PdIr shell, which inhibits oxide formation. These
      results suggest that IrNi@PdIr/C is a promising non-platinum anode catalyst for
      alkaline anion exchange membrane fuel cells.

PMID- 29473929
TI  - A collaborative strategy for stable lithium metal anodes by using three
      dimensional nitrogen-doped graphene foams.
AB  - A collaborative strategy is developed for constructing stable lithium metal
      anodes by using self-supporting three-dimensional nitrogen-doped graphene foams
      as the multifunctional host matrix. The resultant electrode shows impressive
      electrochemical performances, attributable to the three-dimensional porous
      architecture and nitrogen-doping nature of such a unique host matrix.

PMID- 29473930
TI  - Recent developments in intercalation compounds: chemistry and applications.

PMID- 29473931
TI  - Highly durable and biocompatible periodical Si/DLC nanocomposite coatings.
AB  - Functional nanocomposite coatings comprised of periodically stacked nanolayers of
      diamond-like carbon (DLC) and amorphous silicon were developed for biomedical
      applications. The periodical nanocomposite structure provided high surface
      durability while silicon aided in reducing the residual stress. The structural,
      mechanical, tribological, and biomedical properties of the Si/DLC coatings
      deposited by magnetron sputtering were investigated systematically. The effect of
      the negative substrate bias on the structure and properties of the coatings was
      also assessed. The coatings demonstrated high durability and high
      biocompatibility. The bias voltage and bias mode affected both the hardness and
      residual stress of the Si/DLC coatings. Particularly, application of 60 V
      negative bias during the DLC layer deposition resulted in the lowest wear rate.
      FEM simulations showed that the wear resistance of the coatings was dictated by
      the hardness as well as the adhesion between the coatings and a chromium sub
      layer. The periodical alternation of Si and DLC nanolayers led to a significant
      improvement of MC3T3 cell adhesion compared to the previously published data for
      Si-DLC composites.

PMID- 29473932
TI  - Repetitive DNAs and shrink genomes: A chromosomal analysis in nine Columbidae
      species (Aves, Columbiformes).
AB  - An extensive karyotype variation is found among species belonging to the
      Columbidae family of birds (Columbiformes), both in diploid number and
      chromosomal morphology. Although clusters of repetitive DNA sequences play an
      important role in chromosomal instability, and therefore in chromosomal
      rearrangements, little is known about their distribution and amount in avian
      genomes. The aim of this study was to analyze the distribution of 11 distinct
      microsatellite sequences, as well as clusters of 18S rDNA, in nine different
      Columbidae species, correlating their distribution with the occurrence of
      chromosomal rearrangements. We found 2n values ranging from 76 to 86 and nine out
      of 11 microsatellite sequences showed distinct hybridization signals among the
      analyzed species. The accumulation of microsatellite repeats was found
      preferentially in the centromeric region of macro and microchromosomes, and in
      the W chromosome. Additionally, pair 2 showed the accumulation of several
      microsatellites in different combinations and locations in the distinct species,
      suggesting the occurrence of intrachromosomal rearrangements, as well as a
      possible fission of this pair in Geotrygon species. Therefore, although birds
      have a smaller amount of repetitive sequences when compared to other Tetrapoda,
      these seem to play an important role in the karyotype evolution of these species.

PMID- 29473934
TI  - Absence of TERT promoter mutations in colorectal precursor lesions and cancer.
AB  - Hotspot mutations (c.-124bp G > A and c.-146bp G > A) in the promoter region of
      the TERT gene have been recently described in several types of solid tumors,
      including glioma, bladder, thyroid, liver and skin neoplasms. However, knowledge
      with respect to colorectal precursor lesions and cancer is scarce. In the present
      study we aimed to determine the frequency of hotspot TERT promoter mutations in
      145 Brazilian patients, including 103 subjects with precursor lesions and 42 with
      colorectal carcinomas, and we associated the presence of such mutations with the
      patients clinical-pathological features. The mutation analysis was conclusive in
      123 cases, and none of the precursor and colorectal carcinoma cases showed TERT
      promoter mutations. We conclude that TERT mutations are not a driving factor in
      colorectal carcinogenesis.

PMID- 29473933
TI  - Assessment of genetic integrity, splenic phagocytosis and cell death potential of
      (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2
      enoic acid and its effect when combined with commercial chemotherapeutics.
AB  - The increased incidence of cancer and its high treatment costs have encouraged
      the search for new compounds to be used in adjuvant therapies for this disease.
      This study discloses the synthesis of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl
      2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid (IR-01) and evaluates
      not only the action of this compound on genetic integrity, increase in splenic
      phagocytosis and induction of cell death but also its effects in combination with
      the commercial chemotherapeutic agents doxorubicin, cisplatin and
      cyclophosphamide. IR-01 was designed and synthesized based on two
      multifunctionalyzed structural fragments: 4-aminoantipyrine, an active dipyrone
      metabolite, described as an antioxidant and anti-inflammatory agent; and the
      pharmacophore fragment 1,4-dioxo-2-butenyl, a cytotoxic agent. The results
      indicated that IR-01 is an effective chemoprotector because it can prevent
      clastogenic and/or aneugenic damage, has good potential to prevent genomic
      damage, can increase splenic phagocytosis and lymphocyte frequency and induces
      cell death. However, its use as an adjuvant in combination with chemotherapy is
      discouraged since IR-01 interferes in the effectiveness of the tested
      chemotherapeutic agents. This is a pioneer study as it demonstrates the
      chemopreventive effects of IR-01, which may be associated with the higher
      antioxidant activity of the precursor structure of 4-aminoantipyrine over the
      effects of the 1,4-dioxo-2-butenyl fragment.

PMID- 29473936
TI  - Differential survivorship of congeneric ornamental fishes under forecasted
      climate changes are related to anaerobic potential.
AB  - Two Amazonian closely related tetras - cardinal Paracheirodon axelrodi and green
      neon P. simulans - were artificially acclimatized to environmental chambers
      mimicking future climate change scenarios (mild, moderate and extreme), using a
      microcosm facility. P. simulans survived (100%) to all scenarios after 30 days
      exposure, while P. axelrodi presented decreasing survival percentages according
      to environmental severity. These differences may be the reflection of distinct
      natural acclimatization to microhabitats between the species, which differ in
      thermal conditions. Survival responses might be related to differences in
      relative gene expression of lactate dehydrogenase (Ldh), suggesting that P.
      axelrodi anaerobic potential is lower or non-existent compared to P. simulans,
      not tolerating long-term thermal challenges. Accordingly, increases in
      temperature and in CO2 levels caused increases in energy demand and resulted in
      activation of the anaerobic pathway, as demonstrated by the higher enzyme levels
      measured in head and tail portions of both species. Sustained anaerobic
      glycolysis is possible when fish live in challenging environments (low oxygen or
      high temperature). Our results clearly show that P. simulans has a larger scope
      for survival to higher energy demands due to its increased anaerobic potential
      compared to P. axelrodi.

PMID- 29473935
TI  - Dyslexia risk variant rs600753 is linked with dyslexia-specific differential
      allelic expression of DYX1C1.
AB  - An increasing number of genetic variants involved in dyslexia development were
      discovered during the last years, yet little is known about the molecular
      functional mechanisms of these SNPs. In this study we investigated whether
      dyslexia candidate SNPs have a direct, disease-specific effect on local
      expression levels of the assumed target gene by using a differential allelic
      expression assay. In total, 12 SNPs previously associated with dyslexia and
      related phenotypes were suitable for analysis. Transcripts corresponding to four
      SNPs were sufficiently expressed in 28 cell lines originating from controls and a
      family affected by dyslexia. We observed a significant effect of rs600753 on
      expression levels of DYX1C1 in forward and reverse sequencing approaches. The
      expression level of the rs600753 risk allele was increased in the respective
      seven cell lines from members of the dyslexia family which might be due to a
      disturbed transcription factor binding sites. When considering our results in the
      context of neuroanatomical dyslexia-specific findings, we speculate that this
      mechanism may be part of the pathomechanisms underlying the dyslexia-specific
      brain phenotype. Our results suggest that allele-specific DYX1C1 expression
      levels depend on genetic variants of rs600753 and contribute to dyslexia.
      However, these results are preliminary and need replication.

PMID- 29473937
TI  - Large deletion in PIGL: a common mutational mechanism in CHIME syndrome?
AB  - CHIME syndrome is an extremely rare autosomal recessive multisystemic disorder
      caused by mutations in PIGL. PIGL is an endoplasmic reticulum localized enzyme
      that catalyzes the second step of glycosylphosphatidylinositol (GPI)
      biosynthesis, which plays a role in the anchorage of cell-surface proteins
      including receptors, enzymes, and adhesion molecules. Germline mutations in other
      members of GPI and Post GPI Attachment to Proteins (PGAP) family genes have been
      described and constitute a group of diseases within the congenital disorders of
      glycosylation. Patients in this group often present alkaline phosphatase serum
      levels abnormalities and neurological symptoms. We report a CHIME syndrome
      patient who harbors a missense mutation c.500T > C (p.Leu167Pro) and a large
      deletion involving the 5' untranslated region and part of exon 1 of PIGL. In
      CHIME syndrome, a recurrent missense mutation c.500T > C (p.Leu167Pro) is found
      in the majority of patients, associated with a null mutation in the other allele,
      including an overrepresentation of large deletions. The latter are not detected
      by the standard analysis in sequencing techniques, including next-generation
      sequencing. Thus, in individuals with a clinical diagnosis of CHIME syndrome in
      which only one mutation is found, an active search for a large deletion should be
      sought.

PMID- 29473938
TI  - Shared decision-making for prostate cancer screening and treatment: a systematic
      review of randomised controlled trials.
AB  - INTRODUCTION: Men facing prostate cancer screening and treatment need to make
      critical and highly preference-sensitive decisions that involve a variety of
      potential benefits and risks. Shared decision-making (SDM) is considered
      fundamental for "preference-sensitive" medical decisions and it is guideline
      recommended. There is no single definition of SDM however. We systematically
      reviewed the extent of SDM implementation in interventions to facilitate SDM for
      prostate cancer screening and treatment. METHODS: We searched Medline Ovid,
      Embase (Elsevier), CINHAL (EBSCOHost), The Cochrane Library (Wiley), PsychINFO
      (EBSCOHost), Scopus, clinicaltrials.gov, ISRCTN registry, the WHO search portal,
      ohri.ca, opengrey.eu, Google Scholar, and the reference lists of included
      studies, clinical guidelines and relevant reviews. We also contacted the authors
      of relevant abstracts without available full text. We included primary peer
      reviewed and grey literature of randomised controlled trials (RCTs) reported in
      English, conducted in primary and specialised care, addressing interventions
      aiming to facilitate SDM for prostate cancer screening and treatment. Two
      reviewers independently selected studies, appraised interventions and assessed
      the extent of SDM implementation based on the key features of SDM, namely
      information exchange, deliberation and implementation. We considered bi
      directional deliberation as a central and mandatory component of SDM. We
      performed a narrative synthesis. RESULTS: Thirty-six RCTs including 19 196
      randomised patients met the eligibility criteria; they were mainly conducted in
      North America (n = 28). The median year of publication was 2008 (1997-2015).
      Twenty-three RCTs addressed decision-making for screening, twelve for treatment
      and one for both screening and treatment for prostate cancer. Bi-directional
      interactions between healthcare providers and patients were verified in 31 RCTs,
      but only 14 fulfilled the three key SDM features, 14 had at least "deliberation",
      one had "unclear deliberation" and two had no signs of deliberation. CONCLUSIONS:
      There is significant variation in the extent of SDM implementation among studies
      addressing SDM for prostate cancer screening and treatment. Further evaluation of
      these results on patient outcomes, a standardised SDM definition and guidance for
      an effective implementation in several clinical settings are needed.